PMID- 17012061
TI  - Noninvasive brain stimulation in stroke rehabilitation.
AB  - Stroke is a common disorder that produces a major burden to society, largely
      through long-lasting motor disability in survivors. Recent studies have broadened
      our understanding of the processes underlying recovery of motor function after
      stroke. Bilateral motor regions of the brain experience substantial
      reorganization after stroke, including changes in the strength of
      interhemispheric inhibitory interactions. Our understanding of the extent to
      which different forms of reorganization contribute to behavioral gains in the
      rehabilitative process, although still limited, has led to the formulation of
      novel interventional strategies to regain motor function. Transcranial magnetic
      (TMS) and DC (tDCS) electrical stimulation are noninvasive brain stimulation
      techniques that modulate cortical excitability in both healthy individuals and
      stroke patients. These techniques can enhance the effect of training on
      performance of various motor tasks, including those that mimic activities of
      daily living. This review looks at the effects of TMS and tDCS on motor cortical
      function and motor performance in healthy volunteers and in patients with stroke.
      Both techniques can either enhance or suppress cortical excitability, and may
      move to the clinical arena as strategies to enhance the beneficial effects of
      customarily used neurorehabilitative treatments after stroke.

PMID- 17012062
TI  - Imaging motor recovery after stroke.
AB  - Most patients show improvement in the weeks or months after a stroke. Recovery is
      incomplete, however, leaving most with significant impairment and disability.
      Because the brain does not grow back to an appreciable extent, this recovery
      occurs on the basis of change in function of surviving tissues. Brain mapping
      studies have characterized a number of processes and principles relevant to
      recovery from stroke in humans. The findings have potential application to
      improving therapeutics that aim to restore function after stroke.

PMID- 17012063
TI  - Two-photon imaging of synaptic plasticity and pathology in the living mouse
      brain.
AB  - Two-photon microscopy (TPM) has become an increasingly important tool for imaging
      the structure and function of brain cells in living animals. TPM imaging studies
      of neuronal structures over intervals ranging from seconds to years have begun to
      provide important insights into the structural plasticity of synapses and the
      modulating effects of experience in the intact brain. TPM has also started to
      reveal how neuronal connections are altered in animal models of
      neurodegeneration, acute brain injury, and cerebrovascular disease. Here, we
      review some of these studies with special emphasis on the degree of structural
      dynamism of postsynaptic dendritic spines in the adult mouse brain as well as
      synaptic pathology in mouse models of Alzheimer's disease and cerebral ischemia.
      We also discuss technical considerations that are critical for the acquisition
      and interpretation of data from TPM in vivo.

PMID- 17012064
TI  - Behavioral tests for preclinical intervention assessment.
AB  - Select functional outcome tests commonly used for evaluating sensorimotor and
      cognitive capacity in rodents with focal intracerebral ischemic or hemorrhagic
      injury are described, along with upgrades and issues of concern for translational
      research. An emphasis is placed on careful quantitative and qualitative
      assessment of acute and long-term behavioral deficits, and on avoidance of
      frequent pitfalls. Methods for detecting different degrees of injury and
      treatment-related improvements are included. Determining the true potential of an
      intervention requires a set of behavioral analyses that can monitor compensatory
      learning. In a number of preclinical outcome tests, animals can develop
      remarkably effective "tricks" that are difficult to detect but frequently lead to
      dramatic improvements in performance, particularly with repeated practice.
      However, some interventions may facilitate learning without promoting brain
      repair, but these may not translate into a meaningful level of benefit in the
      clinic. Additionally, it is important to determine whether there are any
      preinjury functional asymmetries in order to accurately assess damage-related
      changes in behavior. This is illustrated by the fact that some animals have
      chronic endogenous asymmetries and that others, albeit infrequently, can sustain
      a spontaneous cerebral stroke, without any experimental induction, that can lead
      to chronic deficits as reflected by behavioral, imaging, and histological
      analyses. Finally, a useful new modification of the water maze that involves
      moving the platform from trial to trial within the target quadrant is reviewed,
      and its advantages over the standard version are discussed.

PMID- 17012065
TI  - Issues in selecting outcome measures to assess functional recovery after stroke.
AB  - Most patients who survive a stroke experience some degree of physical recovery.
      Selecting the appropriate outcome measure to assess physical recovery is a
      difficult task, given the heterogeneity of stroke etiology, symptoms, severity,
      and even recovery itself. Despite these complexities, a number of strategies can
      facilitate the selection of functional outcome measures in stroke clinical trial
      research and practice. Clinical relevance in stroke outcome measures can be
      optimized by incorporating a framework of health and disability, such as the
      International Classification of Functioning, Disability, and Health (ICF). The
      ICF provides the conceptual basis for measurement and policy formulations for
      disability and health assessment. All outcome measures selected should also have
      sound psychometric properties. The essential psychometric properties are
      reliability, validity, responsiveness, sensibility, and established minimal
      clinically important difference. It is also important to establish the purpose of
      the measurement (discriminative, predictive, or evaluative) and to determine
      whether the purpose of the study is to evaluate the efficacy or effectiveness of
      an intervention. In addition, when selecting outcome measures and time of
      assessment, the natural history of stroke and stroke severity must be regarded.
      Finally, methods for acquiring data must also be considered. We present a
      comprehensive overview of the issues in selecting stroke outcome measures and
      characterize existing measures relative to these issues.

PMID- 17012066
TI  - Community neurorehabilitation: a synthesis of current evidence and future
      research directions.
AB  - Over the past decade, community neurorehabilitation has emerged as a promising
      extension of neurological rehabilitation. The goal of community
      neurorehabilitation is to maximize functional ability and quality of life through
      multidimensional rehabilitation that occurs while the individual is living in a
      home versus acute or transitory care setting. Because of its multidisciplinary
      focus, many variations of community neurorehabilitation teams have been
      implemented. Critical gaps exist, however, in understanding of the influence of
      structural and procedural differences among programs, as well as patient level
      variables such as social support, on recovery. This paper examines the current
      evidence of the effectiveness of community neurorehabilitation through a review
      of the findings of systematic reviews and meta-analyses of four neurological
      conditions: stroke, multiple sclerosis, traumatic brain injury, and Parkinson's
      disease. It focuses in particular on the data regarding physical therapy and
      occupational therapy, which are two of the primary components of community
      neurorehabilitation programs.

PMID- 17012067
TI  - The epileptogenic zone: general principles.

PMID- 17012068
TI  - The concept of the epileptogenic zone: a modern look at Penfield and Jasper's
      views on the role of interictal spikes.
AB  - In modern times, the determination of the epileptogenic zone demands a
      sophisticated combination of neurophysiological and neuroimaging tools.
      Historically however, the concept of the epileptogenic zone was based on and has
      evolved from the recording of interictal spikes, both in the scalp
      electroencephalogram (EEG) and, particularly, in the acute electrocorticogram
      (ECoG). Because the role of interictal spikes is still not always clear in the
      decision-making process of epilepsy surgery, the relevance of these spikes in the
      definition of the epileptogenic zone is reviewed here, starting with the
      pioneering work of the Montreal school.

PMID- 17012069
TI  - The Bancaud and Talairach view on the epileptogenic zone: a working hypothesis.
AB  - The definition of the epileptogenic zone, as proposed by Talairach and Bancaud,
      is an ictal electro-clinical definition based on the results of stereotactic
      intracerebral EEG (SEEG) recordings. It takes into account not only the
      anatomical location of the "site of the beginning and of the primary
      organization" of the epileptic discharge, but also how this discharge gives rise
      to the accompanying clinical symptoms. This definition is different from the
      North American view since, for the French authors, the epileptogenic zone is not
      synonymous with what can be called the "what-to-remove area". In fact, it is
      above all a conceptual definition which emphazises the importance of studying the
      spatio-temporal dynamics of seizure discharges, and not only their starting
      point.

PMID- 17012070
TI  - Definition of the epileptogenic zone in a patient with non-lesional temporal lobe
      epilepsy arising from the dominant hemisphere.
AB  - Pharmacoresistant epilepsy arising from the dominant temporal region in patients
      with intact memory and normal anatomical imaging, presents major challenges in
      the preoperative definition of the epileptogenic zone, and the planning of the
      extent of the surgical resection. We report on the case of a 42-year-old, right
      handed male who presented with recurrent daily seizures that were resistant to
      antiepileptic drugs. Multiple, non-invasive (scalp) video-EEG evaluations
      revealed focal epilepsy arising from the left fronto-temporal region. Multiple
      high resolution MRIs that were performed at multiple Epilepsy Centers failed to
      show any abnormality. Fluoro-deoxyglucose PET scan showed extensive, left antero
      mesial temporal hypometabolism, and ictal SPECT showed increased perfusion in the
      left insula in addition to the left mesial and anterior temporal pole.
      Neuropsychological testing and intracarotid methohexital testing revealed
      excellent memory to the left, dominant side. A two-stage invasive evaluation with
      subdural grid electrodes followed by depth electrode recordings allowed the
      localization of the epileptogenic region to the temporal pole. A selective
      resection of the left temporal pole (that spared the hippocampal formation)
      resulted in a seizure-free outcome (one year follow-up) with no significant
      consequences on memory function. We conclude that targeted, invasive recording
      techniques should be used for the accurate localization and delineation of the
      extent of the epileptogenic zone in cases of suspected, non-lesional, dominant
      hemisphere, temporal lobe epilepsy with preserved memory function. The use of the
      staged invasive approach may increase the chances for memory (function) sparing
      through tailored, temporal resection.

PMID- 17012071
TI  - Avoid falling into the depths of the insular trap.
AB  - Recent data have demonstrated that insular seizures can mimic those encountered
      in temporal lobe epilepsy (TLE), as well as nocturnal hypermotor attacks
      suggestive of nocturnal frontal lobe epilepsy (NFLE). To illustrate some of the
      issues raised by these observations, we report our first two patients with
      suspected TLE and NFLE, respectively, in whom we originally demonstrated an
      insular ictal onset zone. Patient 1 suffered from daytime seizures characterised
      by a rising and distressing epigastric sensation rapidly followed by oro
      alimentary automatisms, associated with right temporal scalp-EEG ictal discharge.
      Neuroimaging showed consistent right temporal abnormalities, including MRI signs
      of hippocampal sclerosis, anterior and mesial glucose hypometabolism, and mesial
      decrease of benzodiazepine receptors. Intra-cerebral EEG investigation was
      primarily performed because of several ictal signs and symptoms suggesting a
      rapid involvement of the perisylvian region, and showed that the patient suffered
      two types of seizure, one of which arose from the mesial temporal structures, the
      other was sleep-related and originated in the posterior-inferior portion of the
      insula. Anterior temporal lobectomy failed to control this second type of
      seizure. Patient 2 suffered from brief, nocturnal, hypermotor seizures
      characterised by an indefinable aura followed by agitation, body rolling, scream
      and pelvic thrust. Interictal and ictal scalp-EEG failed to detect epileptiform
      discharges, whereas neuroimaging showed left mesial frontal, glucose
      hypometabolism and decreased benzodiazepine receptors associated with a left
      fronto-basal arachnoidal cyst. Invasive EEG monitoring was performed with the aim
      of identifying an orbital or mesial frontal ictal onset, but eventually
      demonstrated that the seizure originated in the anterior-superior portion of the
      left insula. The patient did not undergo surgery and died of SUDEP two years
      later. We discuss the heterogeneity of insular seizure semiology according to
      functional anatomy, the clinical signs and symptoms that might suggest an insular
      ictal onset, the indications and types of invasive EEG monitoring that are needed
      to identify an insular epileptogenic zone definitively, as well as potential
      surgical treatment.

PMID- 17012072
TI  - A case of auditory auras: application of general principles to define and
      localize the epileptogenic zone.
AB  - An illustrative case of auditory aura and complex partial seizures is presented
      to highlight challenges in the accurate localization of the epileptogenic zone.
      Application and interpretation of various diagnostic tools is discussed in this
      case using the North American approach to the localization of the epileptogenic
      zone. Whenever possible, the differences and similarities between the North
      American and the French/Italian approach for the localization of the
      epileptogenic zone are discussed.

PMID- 17012073
TI  - Towards a definition of the "practical" epileptogenic zone: a case of epilepsy
      with dual pathology.
AB  - Presurgical evaluation for patients with drug-resistant epilepsy requires the
      definition of various zones that have a variable spatial relationship with the
      epileptogenic zone. All the available methods to directly measure the actual
      seizure-onset zone and to define "the minimum amount of cortical tissue that must
      be resected to produce seizure-freedom" have significant limitations. We report
      on the case of a patient with dual pathology (hippocampal sclerosis and a post
      traumatic scar) and discuss the contribution of the various presurgical
      investigations that led to surgery and seizure-freedom.

PMID- 17012074
TI  - Girls' schooling in Tanzania: the key to HIV/AIDS prevention?
AB  - This article explores the relationship between schooling for girls and HIV/AIDS
      prevention in the United Republic of Tanzania. It is based on a survey
      administered to upper-level primary school students in rural Tanzania designed to
      ascertain their numeracy and literacy skills as well as their knowledge of
      HIV/AIDS. The findings show that female students generally have stronger literacy
      and numeracy skills but less knowledge about HIV/AIDS than their male
      counterparts. This suggests that general education may not be the best vaccine
      against HIV/AIDS for young women; rather, AIDS-specific education and skills
      training may be required to increase the likelihood of prevention because of
      gender differences in how young people utilize knowledge acquired in school.

PMID- 17012075
TI  - Psychopathology of first-episode psychosis in HIV-positive persons in comparison
      to first-episode schizophrenia: a neglected issue.
AB  - This study aims to detect different psychopathological dimensions in first
      episode psychoses with different underlying causes. We evaluated 22 subjects with
      first-episode psychosis, who differed in biological variables (HIV-positive
      versus HIV-negative) and who were compared by using the Structured Clinical
      Interview for DSM-III-Reviewer, the 18-item Brief Psychiatric Rating Scale
      (BPRS), the 17-item Hamilton Depression Rating Scale, the 14-item Hamilton
      Anxiety Rating Scale and the Mini-Mental State Examination. HIV-positive subjects
      had higher mean scores on the global BPRS and on the paranoid Positive and
      Negative Syndrome Scale subscale compared with HIV-negative subjects. Conversely,
      higher prevalence of affective and anxious symptoms was found in the HIV-negative
      patients in comparison to HIV-positives. HIV-positives had significantly greater
      attention/concentration impairment than HIV-negative persons. In conclusion,
      taking into account psychopathological dimensions may help psychiatrists in
      clinical decision-making regarding the differential diagnosis of psychotic
      symptoms. The psychopathological pattern of first-episode psychosis in HIV
      positive patients may represent an 'elementary model' of acute psychosis
      characterized by paranoid delusions in the absence of the usual affective
      symptoms.

PMID- 17012076
TI  - Safe sex after post-exposure prophylaxis for HIV: intentions, challenges and
      ambivalences in narratives of gay men.
AB  - This paper draws on findings from an on-going prospective cohort study, with a
      quantitative and a qualitative arm, to monitor the implementation of non
      occupational post-exposure prophylaxis (PEP) in Australia. The aim of the
      qualitative arm was to explore in-depth details of exposures to HIV and
      participants' understanding of 'risk'. Of the 328 patients who were enrolled in
      the study from March 1999 to July 2001, 88 (27%) participated in the qualitative
      arm. Interviews were conducted in a semi-structured style and explored the event
      that precipitated the request for PEP, participants' understanding of safe sex,
      their physical and psychological experience of the treatment and the impact that
      the availability of PEP may have on their sexual practices in the future. One
      theme running through the interviews was a determination to either maintain
      existing high levels of safe sex or to increase safe sex practices in those men
      who perceived PEP as 'a wake up call'. This determination was motivated by the
      experience of taking combination therapies and reflection on a potentially HIV
      positive future. However, there were also tensions and ambivalences in the
      narratives. PEP was promoted as an adjunct to safe sex, not as an alternative.
      This is how PEP was understood by the men in this study.

PMID- 17012077
TI  - 'We are no longer called club members but caregivers': Involving youth in HIV and
      AIDS caregiving in rural Zambia.
AB  - This study assessed the strategy of building young people's capacity to provide
      care and support to people living with HIV and AIDS in rural Zambia. Members of
      youth anti-AIDS clubs in schools and communities were trained as adjunct
      caregivers using a locally developed curriculum that allowed them to explore and
      challenge gendered notions of caregiving and emphasized networking with existing
      resources. Results show that caregiving increased among males (47% to 82%) and
      females (41% to 78%). Both sexes provided similar caregiving services, including
      help with household chores and personal care tasks. Youth also undertook
      activities with children to decrease their isolation, help them stay in school,
      and reach additional services. While clients and caregivers reported positive
      aspects of the programme, both reported frustration with the youths' inability to
      meet material needs. This study demonstrates that trained youth already involved
      in anti-AIDS efforts can meet a range of care needs and be valuable assets to
      their community. It also highlights the importance of communicating clearly what
      youth can and cannot do, ongoing monitoring and support of youth caregivers, and
      involving community leaders to give youth credibility and access to local
      resources.

PMID- 17012078
TI  - Overview and implementation of an intervention to prevent adherence failure among
      HIV-infected adults initiating antiretroviral therapy: lessons learned from
      Project HEART.
AB  - Project HEART, an acronym for Helping Enhance Adherence to Retroviral Therapy,
      was a prospective, controlled study to develop, implement, and evaluate a clinic
      based behavioural intervention to prevent adherence failure among HIV-infected
      adults beginning their first highly active antiretroviral therapy (HAART) regimen
      (N = 227). In this paper, we describe the conceptualisation of the Project HEART
      adherence intervention, characteristics of the participants, and lessons learned
      implementing HEART in an inner-city clinic setting. A multi-component
      intervention, HEART combined enhanced education, reminders, adherence feedback,
      social support and adherence-focused problem solving in an integrated manner to
      address common cognitive, motivational, and social barriers to adherence. Unique
      components of the intervention included use of participant-identified adherence
      support partners and a standardized adherence barriers assessment to develop and
      implement individualised adherence plans. Lessons learned regarding the
      feasibility of using participant-identified support partners were as follows. Few
      participants eligible for the study had trouble identifying a support partner.
      Over 90% of support partners attended at least one intervention visit. Support
      partners were most available and amenable to participate early in the initiation
      of therapy. Participants' experiences as the 'supported' partner were generally
      positive. Though many participants faced barriers not easily addressed by this
      intervention (for example, housing instability), formally integrating support
      partners into the intervention helped to address many other common adherence
      barriers. Family and friends are an under-utilised resource in HIV medication
      adherence. Enlisting the help of support partners is a practical and economical
      approach to adherence counselling.

PMID- 17012079
TI  - Social relationships, stigma and adherence to antiretroviral therapy for
      HIV/AIDS.
AB  - Research on adherence to combination antiretroviral therapy has up to now focused
      largely upon problems of definition and measurement, and on the identification of
      barriers and supports. This paper examines the intersection between taking HAART
      and building a life with HIV/AIDS. Data consist of 214 qualitative interviews
      with 52 HIV-positive, active illegal drug users. A interpretive analysis drawing
      upon stigma and fear of disclosure as analytical constructs was applied to
      explain working tensions between efforts to develop social relationships on the
      one hand, and attempts to safeguard health through adherence on the other. The
      analysis specifies a mechanism through which stigma as a social process results
      in marginalization and exclusion. The hierarchical organization of multiple
      stigma is also noted. Loneliness and the desire for relatedness is intensified by
      drug use. Results suggest that persons with HIV/AIDS will not consistently
      subordinate other interests to prioritize adherence. Interventions aimed at
      supporting long-term adherence must address experienced conflicts between
      'health' and 'life'.

PMID- 17012080
TI  - Characteristics of homeless HIV-positive outreach responders in urban US and
      their success in primary care treatment.
AB  - Homeless HIV+ persons with persistent mental illness and substance use disorders
      need services, but are hard to reach and enrol into treatment. Connecting them to
      services is a major challenge of the AIDS epidemic. This report describes
      characteristics of homeless HIV+ substance abusers who responded to outreach and
      enrolled in integrated treatment services. The target population was urban,
      homeless, HIV+ individuals with substance dependence and/or mental illness
      diagnoses. Health and physical functioning were measured using a refinement of
      the Medical Outcomes Study Health Survey. Questions based on the PRIME-MD
      measured subjects' mental health status. Outreach occurred at shelters, soup
      kitchens, and on the streets. The outreach team consisted of a nurse, substance
      abuse counsellor, and a formerly homeless person. Outreach contacted 3,059
      individuals; 1,446 entered the clinic, 110 of 206 eligible candidates enrolled in
      the study, and 82.7% of study participants completed 12-month follow-up
      interviews. Enrollees exhibited 5th percentile composite health scores. They
      reported heavy street drug use and unmet service needs particularly for housing
      and financial assistance. Outreach successfully recruited targeted individuals
      into treatment. They stayed in treatment and demonstrated improvements on
      measures of physical and mental health 12-months later.

PMID- 17012081
TI  - Patterns of reasoning and decision making about condom use by urban college
      students.
AB  - HIV infection rates are rapidly increasing among young heterosexuals, making it
      increasingly important to understand how these individuals make decisions
      regarding risk in sexual encounters. Our objective in this study was to
      characterize young adults' safer sex behaviour and associate this behaviour with
      patterns of reasoning, using cognitive, information processing methods to
      understand the process of sexual risk taking. Sixty urban college students from
      NYC maintained diaries for two weeks and then were interviewed regarding lifetime
      condom use and sexual history. Using cognitive analysis, we characterized four
      patterns of condom use behaviour: consistent condom use (35.0%), inconsistent
      condom use (16.7%), shifting from consistent to inconsistent condom use (35.0%),
      and shifting from inconsistent to consistent condom use (13.3%). Directionality
      of reasoning (i.e. data-driven and hypothesis-driven reasoning) was analysed in
      the explanations provided for condom use decisions. The consistent and
      inconsistent patterns of condom use were associated with data-driven heuristic
      reasoning, where behaviour becomes automated and is associated with a high level
      of confidence in one's judgment. In the other two patterns, the shift in
      behaviour was due to a significant event that caused a change in type of
      reasoning to explanation-based reasoning, reflecting feelings of uncertainty and
      willingness to evaluate their decisions. We discuss these results within the
      framework of identifying potentially high-risk groups (e.g. heterosexual young
      adults) as well as intervention strategies for risk reduction. Further, our
      findings not only identify different patterns of condom use behaviour, but our
      investigation of the cognitive process of decision-making characterizes the
      conditions under which such behaviour and reasoning change.

PMID- 17012082
TI  - Effects of HIV-related stigma among an early sample of patients receiving
      antiretroviral therapy in Botswana.
AB  - Botswana, with its estimated HIV prevalence of 37%, instituted a policy of
      universal access to antiretroviral therapy (ART) in 2002. Initial enrolment
      lagged behind expectations, with a shortfall in voluntary testing that observers
      have attributed to HIV-related stigma - although there are no published data on
      stigma among HIV-positive individuals in Botswana. We interviewed 112 patients
      receiving ART in 2000, finding evidence of pervasive stigma in patterns of
      disclosure, social sequelae, and delays in HIV testing. Ninety-four percent of
      patients reported keeping their HIV status secret from their community, while 69%
      withheld this information even from their family. Twenty-seven percent of
      patients said that they feared loss of employment as a result of their HIV
      status. Forty percent of patients reported that they delayed getting tested for
      HIV; of these, 51% cited fear of a positive test result as the primary reason for
      delay in seeking treatment, which was often due to HIV-related stigma. These
      findings suggest that success of large-scale national ART programmes will require
      initiatives targeting stigma and its social, economic and political correlates.

PMID- 17012083
TI  - Association between risk of acquiring HIV and beliefs and perceptions about the
      lived experience of HIV/AIDS among HIV-negative or untested men who have sex with
      men.
AB  - The study aim was to assess whether the sexual behaviour of HIV-negative or
      untested men who have sex with men (MSM) was related to their perceptions of what
      it is like to live with HIV/AIDS, their beliefs or their attitudes to highly
      active antiretroviral treatments. Any unprotected anal intercourse (UAI) with
      casual partners was used as the sexual-risk indicator. The study enrolled 261
      MSM. There were no significant differences between beliefs, attitudes and
      perceptions about HIV/AIDS, knowledge of post-exposure prophylaxis (PEP) or
      exposure to the HIV/AIDS epidemic among those who had had UAI with casual
      partners and those that had not (P>0.12). Those who considered that low levels of
      viral load and withdrawing before ejaculation reduced the risk of HIV
      transmission were significantly more likely to have had UAI with a casual partner
      (P=0.03). Only a minority of MSM engaging in UAI were optimistic about
      antiretroviral therapy. The study participants were in general pessimistic about
      life with HIV/AIDS despite their risk-taking sexual behaviour.

PMID- 17012084
TI  - Differences between men who report frequent, occasional or no unprotected anal
      intercourse with casual partners among a cohort of HIV-seronegative gay men in
      Sydney, Australia.
AB  - Past research on unprotected anal intercourse with casual partners (UAIC)
      contrasts those who report no UAIC with any UAIC. This paper examines differences
      among three groups of men who had any UAIC on the basis of the number of UAIC
      acts reported in a six-month period, namely no UAIC (n = 507), occasional UAIC (1
      5 acts, n = 251) and frequent UAIC (more than 5 acts, n = 148). The occasional
      UAIC group had values lying between those of the no- and the frequent-UAIC group.
      As compared with the frequent-UAIC group, men in the occasional-UAIC group were
      less likely to have a steady partner, held less favorable attitudes toward
      condoms and higher levels of HIV treatments optimism and were more likely to
      report some disclosure of serostatus to or by casual partners and a range of
      esoteric sexual practice. On the other hand, men in the no-UAIC group had lower
      levels of 'feeling bad' (distress) and were less likely to use drugs to enhance
      sexual pleasure in casual encounters. Disclosure of serostatus had a strong
      association with frequent UAIC and this finding calls for both more research and
      more community exploration of issues surrounding sexual decision-making.

PMID- 17012085
TI  - HIV-disclosure in the context of vertical transmission: HIV-positive mothers in
      Johannesburg, South Africa.
AB  - HIV-disclosure among childbearing women remains poorly understood, particularly
      in sub-Saharan Africa. This paper chronicles disclosure experiences of 31 women
      attending prevention of mother-to-child HIV transmission services in
      Johannesburg. Data collection entailed repeat in-depth interviews over a nine
      month period. Virtually all women (93.5%) had told at least one person (usually a
      partner), most voluntarily and within a week of the test result. Secondary
      disclosure was most likely with female family members, through indirect means and
      involuntary. Confidentiality breach by primary targets likely contributed to the
      observed high rates of involuntary secondary disclosure and negative secondary
      disclosure experiences. For most mothers, voluntary disclosure was driven by the
      desire to ensure adequate infant care and avoid vertical HIV transmission. The
      impact of disclosure was not always clear-cut. While most primary disclosure
      experiences were ultimately constructive, secondary disclosure more likely led to
      rejection, stigmatization and the withholding of financial support. Our data
      illustrate the influence of social contextual factors on disclosure patterns and
      impact. For these mothers, socio-cultural norms, the current media and political
      environment surrounding HIV/AIDS, household composition and social networks and
      childbearing status shaped disclosure experiences; sometimes constraining
      disclosure circumstances and sometimes creating a safe space to disclose.
      Programmatic implications are also discussed.

PMID- 17012086
TI  - Violence and HIV-related risk among young men who have sex with men.
AB  - Limited research has been conducted on threats or violence by family members and
      sexual partners against young men who have sex with men (MSM). Young MSM, aged 15
      22 years, who attended public venues in New York City were enrolled in an
      anonymous, cross-sectional HIV seroprevalence and risk-behavior study. About two
      thirds (68%) of the young MSM reported ever experiencing threats or violence from
      either family or partners and 25% reported threats or violence by both family and
      partners. In multivariate analysis, threats or violence by partners was
      significantly associated with older age, a history of forced sex and a history of
      running away from home. Recent unprotected anal sex and club drug use were
      significantly associated with a history of threats or violence by both family and
      partners. HIV prevention interventions need to include multiple factors that may
      have an impact on risk, including substance use and abuse, anti-violence and
      other mental-health issues.

PMID- 17012087
TI  - Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian
      populations.
AB  - We undertook this study to provide a profile of Aboriginal people initiating
      antiretroviral therapy and their response to treatment. Aboriginal peoples were
      identified through self-report. Baseline socio-demographics and risk factors were
      compared between Aboriginal and non-Aboriginal participants as were baseline
      factors associated with two consecutive plasma viral load measures below 500
      copies/ml using contingency table analysis. Multivariate survival analysis of the
      prognostic factors associated with time to two consecutive plasma viral load
      measures below 500 copies/ml among eligible participants was undertaken to
      characterize response to antiretroviral therapy. There were 892 participants with
      available data for this analysis, of those 146 (16%) self-identified as
      Aboriginal. Aboriginal participants were more likely to be female (p < or =
      0.001), have lower baseline plasma viral loads (p = 0.010), be co-infected with
      HCV (p < 0.001), live in unstable housing (p < or = 0.001), and report an income
      of >10K CDN (p < or = 0.001) per annum. Aboriginal people were less likely to
      report men who have sex with men (p < or = 0.001) and more likely to report
      injection drug use (p < or = 0.001) as a risk factor for HIV infection.
      Aboriginal participants were more likely to receive double versus triple
      combination antiretroviral therapy (p = 0.002), be less adherent in the first
      year on therapy (p = 0.001) and to have a physician less experienced with
      treating HIV (p < or = 0.001). When these factors were controlled for, Aboriginal
      people treated with triple combination therapy were as likely to respond and
      suppress their viral load below 500 copies. In the era of HAART, our results
      indicate that Aboriginal people living with HIV/AIDS were less likely to receive
      optimal therapy. However, when Aboriginals did receive triple drug therapy they
      suppressed just as well as non-Aboriginals.

PMID- 17012088
TI  - Illness-related factors, stress and coping strategies in relation to
      psychological distress in HIV-infected persons in Hong Kong.
AB  - This study examined the relationships among illness-related factors, stress,
      coping strategies and psychological distress in HIV-infected persons in Hong Kong
      (N=118). Multiple regression analyses were used to examine the models of
      psychological distress as a function of demographic factors, illness-related
      factors, psychosocial stressors and coping. Results showed that positive thinking
      was inversely related to psychological distress and avoidance was associated with
      higher level of anxiety. However, the use of problem solving was found to be
      inversely related to anxiety. Results are discussed in the context of Chinese
      culture and the service in Hong Kong.

PMID- 17012089
TI  - Communication of HIV viral load to guide sexual risk decisions with
      serodiscordant partners among San Francisco men who have sex with men.
AB  - The objective of this study was to estimate frequency and correlates of
      discussing HIV viral load (VL) with serodiscordant sex partners to guide
      decisions about sexual activities among men who have sex with men (MSM). We
      conducted a cross-sectional survey of 573 San Francisco MSM. Among 507 who knew
      their HIV status, 397 (78%) were familiar with the term 'viral load', and half
      (n=199) had a serodiscordant partner in the prior year. These 199 respondents
      (n=130 [65%] HIV-positive; n=69 [35%] HIV-negative) were the focus of this
      analysis. A majority (n=111, 56%) discussed VL in the prior year with
      serodiscordant partners specifically to guide decisions about sexual risk
      behaviour. Discussion was more common among HIV-positive than HIV-negative
      participants (adjusted odds ratio [AOR], 3.5; 95% confidence interval [CI], 1.6
      7.6), and African Americans compared to whites (AOR, 3.7; 95% CI, 1.5-9.5). HIV
      negative men who discussed VL were more concerned about becoming infected, but
      also more willing to engage in risky behaviour with a partner whose VL is
      undetectable, than men not discussing VL. Some HIV-negative men may be discussing
      VL to engage in higher risk behaviour upon learning of an HIV-positive partner's
      undetectable VL. Interventions targeting MSM should explain that while risk of
      transmission is likely reduced with a low blood plasma VL, it is not necessarily
      eliminated.

PMID- 17012090
TI  - Barebacking websites: electronic environments for reducing or inducing HIV risk.
AB  - Barebacking, or intentional unprotected anal intercourse (UAI), among men who
      have sex with men (MSM) has been a growing concern for the public health
      community because of UAIs link to HIV incidence and sexually transmitted
      infections (STIs). Men who bareback have created online spaces through websites
      that host thousands of profiles throughout the US and world. Adapting two domains
      from person-environment theory, this study contrasted the health messages
      surrounding the risks of UAI within two mainstream US-based barebacking websites.
      One website developed intensive systems to promote harm reduction, such as
      encouraging frequent HIV-testing, discussing STIs with partners, and limiting the
      number of partners. In contrast, the other site analysed negated the seriousness
      of HIV and STIs, which can have clear negative outcomes for patrons whom relied
      on this information. This analysis implicates the need to explore electronic
      environments as viable tools for HIV prevention and programme development.

PMID- 17012091
TI  - Body image in middle-aged HIV-infected and uninfected women.
AB  - We assessed factors associated with negative body image among 225 HIV-infected
      and 207 uninfected women. Standardized interviews obtained sociodemographic data
      and elicited agreement with the statement: 'Overall I am satisfied with my body
      shape'. Height and weight were measured. Overall, 39% of the women were obese and
      47% had a negative body image. Factors independently associated with negative
      body image were HIV-infection, BMI, and depression. Given the high prevalence of
      obesity and negative body image, interventions aimed at assisting women with
      weight loss are warranted.

PMID- 17012092
TI  - Knowledge, attitudes and sources of information regarding HIV/AIDS in Iranian
      adolescents.
AB  - The World Health Organization recently reported an 'alarming trend' of increasing
      Human Deficiency Virus (HIV) infection in the Islamic Republic of Iran.
      Adolescents form a particularly important target group for primary prevention. An
      anonymous questionnaire, derived from standard surveys such as the Safer Choices
      questionnaire and the 2001 Youth Risk Behavior Survey, was distributed to 1227
      Iranian students attending 19 randomly selected high schools in Hashtgerd in
      2002. Students reported that television (84%) and school teachers (66%) were the
      best sources of HIV/AIDS information, while parents (27%) and school books (15%)
      were least informative. Most students knew that heterosexual intercourse (90%)
      and shared intravenous needles (94%) can cause HIV infection; however, salient
      misconceptions were revealed. Only 53% were aware that condoms protect against
      infection through sexual intercourse. More effective school-based HIV/AIDS
      education is needed in Iran.

PMID- 17012093
TI  - Perceived stress in HIV-infected individuals: physiological and psychological
      correlates.
AB  - The purpose of this study was to determine the correlation of perceived stress
      with selected physiological and psychological factors in an HIV-infected,
      predominantly African American population and to assess the multivariable effects
      on perceived stress. The variables that correlated significantly with perceived
      stress were entered into a backward stepwise regression model. Pearson's r
      analysis showed significant correlations between perceived stress and state and
      trait anxiety, depression, HIV-related symptoms, sleep quality, daytime
      sleepiness and fatigue. State and trait anxiety, depression and fatigue retained
      significance (p<0.1) in the final regression model. These factors explained
      approximately 80% of the variance in perceived stress. The significant
      interactions of multiple physiological and psychological correlates suggest that
      perceived stress is a complex outcome with a multifactorial etiology. Further,
      the model suggests that psychological factors may contribute to perceived stress
      in this population more than physiological factors such as HIV-related
      symptomatology or stage of disease.

PMID- 17012094
TI  - A community-based rapid assessment of HIV behavioural risk disparities within a
      large sample of gay men in southeastern USA: a comparison of African American,
      Latino and white men.
AB  - Because the southeastern USA is experiencing a disproportionate HIV infection
      rate compared to other regions of the country, we explored HIV behavioural risk
      disparities by race/ethnicity among self-identifying gay men. Conceived and
      implemented as a community-based participatory research (CBPR) study, this rapid
      assessment collected demographic and HIV risk-behaviour data from men in five gay
      bars in the northwestern part of the state of North Carolina, using an assessment
      available in English and Spanish. Of 719 participants, 34.8% reported
      inconsistent condom use during anal intercourse in the past three months, 11.4%
      reported ever having had a sexually transmitted disease (STD), 3.6% reported
      being HIV-seropositive and 26% reported illicit drug use during the past 30 days.
      Compared to white participants, African American/black and Hispanic/Latino
      participants were more likely to report inconsistent condom use during anal
      intercourse with multiple partners during the past three months. African
      American/black participants were more likely to report illicit drug use during
      the past 30 days. Hispanic/Latino participants were more likely to have never
      been tested for HIV. Rates of HIV risk behaviours among gay men remain high and
      racial/ethnic differences indicate the need for targeted and tailored prevention
      strategies.

PMID- 17012095
TI  - Improving well-being through psycho-education among voluntary counseling and
      testing seekers in Nigeria: a controlled outcome study.
AB  - The present study evaluated the efficacy of an individualized psycho-education
      (PE) program in reducing psychological distress and risky sexual behavior and
      enhancing self-disclosure associated with an HIV diagnosis among attendees of a
      walk-in non-governmental voluntary counseling and testing (VCT) center in
      Nigeria. Ninety-four consecutive individuals were asked to complete a pre
      counseling, baseline questionnaire detailing their sociodemographic
      characteristics, psychopathology, sexual practices, self-disclosure intention and
      coping behaviors. They were screened for HIV and post-test counseled. Sixty-seven
      individuals (72.2%) who tested positive were consecutively randomly assigned to
      one of two groups: a PE program (four 60-minute weekly manual driven sessions)
      (N=34) and a wait-list (WL) control group (N=33). The major outcome measures used
      were the Crown Crisp Experiential Index (CCEI), the Beck Depression Inventory
      (BDI) (Beck et al., (1961), self-report sexual practices in past three months,
      self-disclosure intention and the brief COPE. At four weeks post-intervention,
      significant reductions on all measures as well as reduction in risky sexual
      practices were observed in the treatment group compared with the wait-list group.
      Treatment group members were also significantly more likely to disclose their
      serostatus and accept their HIV status as a way of coping, compared with the wait
      list group. Overall, support was found for the efficacy of a manual-driven PE
      program for self-disclosure, reduction of depression and improvement in safe
      sexual practices.

PMID- 17012096
TI  - The role of sympathy on avoidance intention toward persons living with HIV/AIDS
      in Jamaica.
AB  - As the number of persons living with HIV/AIDS (PLWHA) continues to increase in
      Jamaica, concerns of attitudes become more important. As such, the objective of
      the present study is to examine the attitudes of university students in Jamaica
      toward PLWHA including sympathy and avoidance intentions. A large sample of
      university students (N=1,252) was surveyed between June 2001 and February 2002
      using a 193-item questionnaire that measured HIV-related knowledge, attitudes and
      behaviors. Results revealed that less than half of the students reported
      sympathetic attitudes toward homosexual males or female prostitutes living with
      HIV/AIDS (41% and 44%, respectively) while the majority reported sympathetic
      attitudes toward heterosexual males and non-prostitute females living with the
      disease (67% and 81%, respectively). Most students (80%) reported no avoidance
      intentions toward family members or friends living with the disease. Sympathy,
      HIV knowledge, education and awareness were associated with no avoidance
      intention of HIV-positive family members and friends. These findings suggest that
      sympathy could be important in improving prosocial intentions toward PLWHA and
      warrants further research.

PMID- 17012097
TI  - Physical activity in a cohort of HIV-positive and HIV-negative injection drug
      users.
AB  - Physical activity is beneficial for persons with HIV infection but little is
      known about the relationships between physical activity, HIV treatment and
      injection drug use (IDU). This study compared physical activity levels between
      HIV-negative and HIV-positive injection drug users (IDUs) and between HIV
      positive participants not on any treatment and participants on highly active
      antiretroviral therapy (HAART). Anthropometric measurements were obtained and an
      interviewer-administered modified Paffenbarger physical activity questionnaire
      was administered to 324 participants in a sub-study of the AIDS Linked to
      Intravenous Experiences (ALIVE) cohort, an ongoing study of HIV-negative and HIV
      positive IDUs. Generalized linear models were used to obtain univariate means and
      to adjust for confounding (age, gender, employment and recent IDU). Vigorous
      activity was lower among HAART participants than HIV-positive participants not on
      treatment (p=0.0025) and somewhat lower than HIV-negative participants (p=0.11).
      Injection drug use and viral load were not associated with vigorous activity.
      Energy expenditure in vigorous activity was also lower among HAART participants
      than both HIV-negative and HIV-positive participants not on treatment. Thus, HIV
      positive participants on HAART spend less time on vigorous activity independent
      of recent IDU. More research is needed into the reasons and mechanism for the
      lack of vigorous activities, including behavioral, psychological and
      physiological reasons.

PMID- 17012098
TI  - Circuit parties: sexual behaviors and HIV disclosure practices among men who have
      sex with men at the White Party, Palm Springs, California, 2003.
AB  - The syphilis epidemic among men who have sex with men (MSM) in major US cities
      and concomitant increases in high-risk sexual behavior, have raised concerns of
      increased HIV transmission in this population. Therefore, to provide information
      for health promotion and disease awareness efforts, we investigated sexual
      behaviors, partner selection preferences and HIV serostatus disclosure practices
      of MSM at the White Party in Palm Springs, California. Circuit party attendees
      reported engaging in unprotected anal sex, however, a high proportion reported
      disclosing their HIV status. These findings suggest that some gay men are
      serosorting as a risk reduction strategy or implementing sexual risk reduction
      strategies to protect themselves and their partners. In our study, HIV-negative
      men were nine times more likely to report a preference for a seroconcordant
      sexual partner. The self-protecting attitudes of HIV-negative men in our sample
      outweighed the partner-protecting attitudes of HIV-positive men. This suggests
      that prevention interventions focusing on HIV-positive persons are warranted.

PMID- 17012099
TI  - Growing up: perspectives of children, families and service providers regarding
      the needs of older children with perinatally-acquired HIV.
AB  - Children with perinatally-acquired HIV are living into adolescence and adulthood.
      As this is a relatively new phenomenon, there is a paucity of research
      highlighting the complex issues that arise for these children. This qualitative
      case-study examines the needs of a select group of older children (9-16 years
      old) with perinatally-acquired HIV in the province of British Columbia, Canada
      through focus groups and interviews conducted with ten HIV-infected children, 11
      family members and 11 service providers. The needs of this population are
      diverse, reflecting its heterogeneity. However, participants consistently
      highlighted issues of stigma, sexual health and mental health as major areas of
      current and future concern. Continued support, education and future planning in
      these areas are necessary for older HIV-infected children as they transition out
      of childhood.

PMID- 17012101
TI  - Ovariotomy for menstrual madness and premenstrual syndrome--19th century history
      and lessons for current practice.
AB  - Ovariotomy--the removal of normal ovaries, known as Battey's Operation--began in
      1872 and became the fashionable treatment of menstrual madness, neurasthenia,
      nymphomania, masturbation and "all cases of insanity". This practice was
      supported by distinguished gynecologists and psychiatrists, becoming one of the
      great medical scandals of the 19th century. In modern times, if menstrual madness
      is considered to be premenstrual dysphoric disorder (PMDD), and ovariotomy, the
      surgical equivalent of ovulation suppression of GnRH analogues, it can be argued
      that the surgery would have been effective for this limited indication, although
      the side effects of long-term estrogen deficiency would have made the treatment
      unacceptable. Currently, the successful hormonal treatment of PMDD is one of
      suppression of ovulation and removal of the cyclical hormonal changes in the
      luteal phase, probably progesterone, which is the essential cause of PMDD. Such
      therapy would be by GnRH analogues, transdermal estradiol and, in a few cases,
      the surgical option of hysterectomy and bilateral salpingo-oophorectomy with
      adequate hormone replacement. A study of medical history can help us prevent the
      mistakes of over-enthusiasm but positive lessons can be learned.

PMID- 17012102
TI  - Colorectal cancer in middle-aged women in relation to hormonal status: a report
      from the Women's Health in the Lund Area (WHILA) study.
AB  - OBJECTIVE: To delineate a perceived association of estradiol versus estradiol
      plus norethisterone hormone therapy on the prevalence of colorectal cancer in
      postmenopausal women. METHODS: The Women's Health in the Lund Area (WHILA)
      project covers 10,766 women aged 50-60 years, living in the Lund area, Sweden.
      Out of this population, 6908 (64%) women completed questionnaires, underwent
      physical and laboratory assessments and had self-reported information regarding
      colorectal cancer. Four hundred and twenty-two (6%) were premenopausal (PM), 3600
      (52%) were postmenopausal without hormone therapy (PM0), 2452 (36%) were
      postmenopausal with combined hormone therapy (PMT-HT) and 364 (5%) were
      postmenopausal with estrogen monotherapy (PMT-E). RESULTS: There were 21 cases of
      colorectal cancer (0.3%), one in the PM group, 16 in the PM0 group, two in the
      PMT-HT group and another two in the PMT-E group. Colorectal cancer prevalence was
      lower in the PMT-HT than in the PM0 group (odds ratio (OR) = 0.18, 95% confidence
      interval (CI) = 0.04-0.80). However, for the PMT-E group, the OR (95% CI) was
      1.02 (0.86-1.20). There was a positive association between low physical activity
      (p = 0.04), low parity (p = 0.02) and risk of colorectal cancer. CONCLUSION:
      Combined hormone therapy seemed to be associated with a lower risk of colorectal
      cancer in postmenopausal women in contrast to estrogen monotherapy. Hence the
      progestin might have a protective role.

PMID- 17012103
TI  - Breast cancer in postmenopausal women with and without hormone replacement
      therapy: preliminary results of the MISSION study.
AB  - OBJECTIVES: To determine breast cancer prevalence in postmenopausal women with or
      without hormone replacement therapy (HRT). PATIENTS AND METHODS: This was a
      historical-prospective study with random patient selection. Patients were
      recruited between January 2004 and February 2005, and allocated to two groups:
      the 'treated group' comprising postmenopausal women on HRT regimens commonly
      prescribed in France or who had stopped <5 years previously; or the 'untreated
      group' of postmenopausal women who had never received HRT or stopped >5 years
      previously. RESULTS: In total 6755 patients fulfilled all inclusion criteria:
      3383 in the treated group and 3372 in the untreated group. The treated group was
      younger and less overweight than the untreated group (p < 0.0001). The treated
      group had fewer late menopauses (p = 0.0002) and fewer first-degree family
      histories of breast cancer (p < 0.0001). Mean HRT duration was 7.9 years; 30.5%
      of women were treated for >or=10 years. Breast cancer prevalence was 1.01% for
      the treated group and 6.21% for the untreated group. The European standardized
      incidence rate of breast cancer in the untreated group was significantly higher
      than in the French reference population (comparative incidence figure ratio
      (CIFR) = 2.24; 95% confidence interval (CI) = 1.50-3.36). In contrast, the
      European standardized incidence rate in the treated group on the studied HRT
      regimens (excluding some progestins) was not significantly different from that of
      the reference population (CIFR = 1.04; 95% CI = 0.35-3.15). CONCLUSION: The
      differences between the two groups may be due to French gynecologists' treatment
      strategy of avoiding prescribing HRT to high-risk women, and also perhaps to a
      specific 'studied HRT' effect.

PMID- 17012104
TI  - Reduced aromatase activity in granulosa cells of women with endometriosis
      undergoing assisted reproduction techniques.
AB  - The aim of the present study was to measure the in vitro aromatase activity in
      granulosa cells of women with endometriosis submitted to assisted reproduction
      techniques. A case-control study was conducted on eight patients with
      endometriosis and eight with other infertility causes submitted to in vitro
      fertilization or intracytoplasmic sperm injection. Granulosa cells were obtained
      from pre-ovulatory follicles during oocyte retrieval and cultured for 24 h in the
      presence or absence of testosterone (2 x 10(-6) and 2 x 10(-5) M), follicle
      stimulating hormone (FSH) and insulin-like growth factor-I (IGF-I) (both at 50
      ng/ml). Estradiol (radioimmunoassay) was measured in the obtained culture fluids.
      The basal production of estradiol and its production under testosterone addition
      to the culture (aromatase activity) were analyzed. Reduced aromatase activity was
      detected in cultured granulosa cells in endometriosis cases, compared with
      controls, when testosterone was added at the concentration at 2 x 10(-6) M (p =
      0.0303). The basal production of estradiol was also reduced in endometriosis
      patients (p = 0.0390). The effect of addition of FSH and IGF-I did not differ
      between groups. In conclusion, the in vitro basal production of estradiol and
      aromatase activity in granulosa cells were reduced in women with endometriosis
      submitted to assisted reproduction techniques, compared with the control group.

PMID- 17012105
TI  - Substituting human chorionic gonadotropin by gonadotropin-releasing hormone
      agonist to trigger final follicular maturation, during controlled ovarian
      hyperstimulation, results in less systemic inflammation.
AB  - BACKGROUND: To investigate the degree of systemic inflammation, as reflected by
      serum C-reactive protein (CRP) levels, associated with controlled ovarian
      hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin
      releasing hormone (GnRH) agonist for the induction of final follicular
      maturation. DESIGN: Prospective, observational study. SETTING: An in vitro
      fertilization (IVF) unit of an academic medical center. PATIENTS: Twenty-four
      women undergoing COH and IVF with the flexible GnRH antagonist protocol were
      prospectively assigned to receive hCG or GnRH agonist for the induction of final
      follicular maturation. METHODS: Blood was drawn three times during COH for
      measurement of sex-steroid and CRP levels: the day on which adequate suppression
      was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and
      (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time
      points in the two groups. RESULTS: No between-group differences were observed in
      terms of patient age, gonadotropin dosage, duration of stimulation or number of
      oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on
      Day-hCG and Day-0, but the difference was significant only in the hCG group
      (p<0.03 for both). The percentage change in CRP levels after hCG administration
      (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%).
      CONCLUSION: Administration of GnRH agonist in patients undergoing COH for IVF
      yields a lesser degree of systemic inflammation, as reflected by CRP levels, than
      hCG.

PMID- 17012106
TI  - Factors associated with quality of life in a cohort of postmenopausal women.
AB  - OBJECTIVE: To evaluate quality of life (QOL) and identify its associated factors
      in a cohort of postmenopausal women who had not received hormone therapy.
      METHODS: A cross-sectional study was conducted among 81 postmenopausal women who
      had not used hormone therapy in the last six months. Sociodemographic and
      clinical characteristics, in addition to the prevalence of menopausal symptoms,
      were evaluated. QOL was assessed by the Medical Outcomes Study 36-item Short-Form
      Health Survey (SF-36) questionnaire, which may be condensed into two summaries:
      Physical Component Summary and Mental Component Summary. Generalized linear
      models were used to analyze the data, allowing the identification of factors
      affecting QOL, adjusting for confounding variables. RESULTS: The mean (+/
      standard deviation) age of the participants was 58.1 +/- 4.7 years. The most
      prevalent symptoms were nervousness (67%) and hot flushes and sweating (51%).
      Factors associated with poorer QOL were sweating, palpitations, nervousness
      (physical component), and dizziness, nervousness, depression, insomnia and
      dyspareunia (mental component). CONCLUSION: We observed that menopausal symptoms
      negatively affected the physical and mental components of QOL in postmenopausal
      women.

PMID- 17012107
TI  - The metabolic syndrome among postmenopausal women in Ecuador.
AB  - BACKGROUND: The prevalence of the metabolic syndrome increases with age and after
      the onset of menopause, and may explain in part the apparent acceleration of
      cardiovascular disease in postmenopausal women. OBJECTIVE: To determine the
      prevalence of metabolic syndrome and related risk determinants among
      postmenopausal women in Ecuador. METHODS: Postmenopausal women >or=40 years of
      age, non-users of hormone therapy and with an intact uterus, were asked to
      participate in a metabolic syndrome screening and educational program at the
      Institute of Biomedicine of the Universidad Catolica of Guayaquil, Ecuador.
      Sociodemographic data, waist circumference and blood pressure measurements were
      recorded, and a fasting blood sample obtained for serum glucose and lipid profile
      determinations. Woman were counseled and managed according to the results.
      Metabolic syndrome was defined in accordance with the criteria of the Third Adult
      Treatment Panel (ATP III). RESULTS: Three hundred and twenty-five postmenopausal
      women entered the program. Mean (+/-standard deviation) age was 55.9 +/- 8.1
      years, 53.5% of them were aged >or=54 years (median). The prevalence of metabolic
      syndrome, according to ATP III criteria, was 41.5%. Using the same criteria,
      38.8%, 16.6%, 56.9% and 54.2% of the women presented with hypertension, diabetes,
      hypertriglyceridemia and abdominal obesity, respectively. More than 40% of women
      determined to have hypertension or diabetes lacked knowing so. Logistic
      regression analysis determined that age increased the risk of presenting
      hypertension and diabetes (odds ratio (95% confidence interval): 2.0 (1.2-3.2)
      and 1.6 (0.9-3.0), respectively, p < 0.05), entities which in turn duplicated the
      risk of having high triglyceride levels. Sedentary women with <5 years since
      menopause onset were at higher risk of having abdominal obesity, which was
      directly related to diabetes and hypertension. CONCLUSIONS: In this
      postmenopausal Ecuadorian population the prevalence of the metabolic syndrome was
      high and its determinant factors related to age, time since menopause onset and
      sedentary habits. Because of the implications for cardiovascular risk, counseling
      programs directed toward high-risk populations should be encouraged.

PMID- 17012108
TI  - Effect of vitamin K2 treatment on carboxylation of osteocalcin in early
      postmenopausal women.
AB  - OBJECTIVE: We examined the serum level of undercarboxylated osteocalcin (uc OC),
      which is a sensitive marker of vitamin K status, and levels of bone turnover
      markers in early postmenopausal women receiving vitamin K2 treatment with or
      without vitamin D3. METHODS: Thirty-four postmenopausal women with a mean age of
      53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia
      and osteoporosis) were treated with vitamin K2 or with a combination of vitamin
      K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg
      vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2
      plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact
      osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline
      (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2
      years after the start of treatment. RESULTS: Serum uc OC levels in women treated
      with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased
      significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with
      vitamin K2 did not show significant changes, while those in women who received
      the combined treatment decreased significantly (p < 0.05). On the other hand,
      urinary DPD level in women treated with vitamin K2 did not change, while that in
      women who received the combined treatment tended to decrease (p < 0.1).
      CONCLUSION: Serum uc OC levels in early postmenopausal women who received vitamin
      K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2
      and vitamin D3 may be effective for sustaining BMD in early postmenopausal women
      whose bone turnovers are highly activated.

PMID- 17012109
TI  - Serum vascular endothelial growth factor as a possible indicator of arterial
      reactivity in postmenopausal women.
AB  - OBJECTIVE: To determine whether serum vascular endothelial growth factor (VEGF)
      concentration is correlated with arterial reactivity in postmenopausal women.
      METHODS: An observational study was conducted on 24 postmenopausal women who did
      not receive any hormone therapy in the 6 months preceding the study and had no
      pre-existing cardiovascular diseases or cardiovascular risk factors. Serum
      samples were obtained from all participants and analyzed for VEGF concentrations.
      Arterial reactivity was assessed by the measurement of endothelium-dependent
      dilatation and endothelium-independent dilatation of the brachial artery, using
      color duplex Doppler ultrasound. RESULTS: The study population was aged 50.8
      years on average, with about 2 years of menopause. Serum VEGF concentration in
      postmenopausal women was significantly correlated with both endothelium-dependent
      dilatation (r = -0.66, p < 0.01) and endothelium-independent dilatation (r = 
      0.65, p < 0.01) of the brachial artery. CONCLUSIONS: Serum VEGF level may be a
      potential indicator of arterial reactivity in postmenopausal women.

PMID- 17012110
TI  - Vascular endothelial growth factor and basic fibroblast growth factor in
      polycystic ovary syndrome during controlled ovarian hyperstimulation.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that
      causes anovulation and consequent subfertility. It is well established that
      increased ovarian mass, supported by new blood vessel proliferation in stroma and
      theca, is a key feature of PCOS. Recent studies suggest a role for angiogenetic
      factors in this phenomenon. AIM: To evaluate of levels of vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum and
      follicular fluid of PCOS patients during a controlled ovarian hyperstimulation.
      METHODS: In 52 patients undergoing in vitro fertilization treatments, 26 PCOS
      patients and 26 controls, serum VEGF and bFGF levels were assessed before
      starting administration of follicle-stimulating hormone (FSH) (day 0), on the day
      of administration of human chorionic gonadotropin (hCG) and on the day of oocyte
      retrieval. Follicular fluid levels of the two growth factors were detected on the
      day of oocyte retrieval. RESULTS: PCOS patients showed higher serum VEGF levels
      than controls before starting FSH administration, on the day of hCG
      administration and on the day of oocyte retrieval. Serum VEGF levels showed a
      rise after hCG administration only in the PCOS patients. In addition, serum bFGF
      levels were higher in PCOS patients than in controls on the day of hCG
      administration and the day of oocyte retrieval. Furthermore, on the day of hCG
      administration, serum bFGF levels were directly correlated to the amount of FSH
      previously administered (p < 0.0001). In follicular fluid, higher VEGF and bFGF
      levels were found in PCOS patients than in controls. Furthermore, follicular
      fluid bFGF concentrations were inversely correlated with the percentage of mature
      oocytes collected (p < 0.05). CONCLUSIONS: The present study revealed elevated
      levels of VEGF and bFGF in serum and follicular fluid in PCOS patients compared
      with controls. bFGF seems to be an FSH-dependent growth factor and its levels in
      follicular fluid are inversely correlated with the percentage of mature oocytes
      collected.

PMID- 17012111
TI  - Closure of restrictive ventricular septal defects through a right axillary
      thoracotomy.
AB  - OBJECTIVE: To report the midterm results of an alternative minimally invasive
      approach for closure of ventricular septal defects (VSD) through a muscle-sparing
      minithoracotomy at the right midaxillary line. MATERIAL AND METHODS: From
      September 2003 to December 2005, 22 patients (median age, 5 years; range, 1.5-12
      years) underwent a right lateral axillary thoracotomy for closure of a
      perimembranous VSD. Special features of the approach included an incision between
      the anterior and posterior axillary fold, a muscle-sparing preparation over the
      fourth intercostal space, and the establishment of cardiopulmonary bypass with
      inguinal and superior vena cava cannulation. The ascending aorta was cross
      clamped and cardioplegic arrest was instituted. The VSDs were all approached
      through a right atriotomy and closed directly (17 patients) or with a patch (5
      patients). Three patients underwent concomitant aortic valve repair. RESULTS:
      There was no mortality or significant surgical morbidity. Median cross-clamp and
      cardiopulmonary bypass times were 46 and 104 min, respectively. Follow-up was
      complete and ranged from 2 to 22 months (median, 20 months). All patients were in
      sinus rhythm. Echocardiography revealed no residual defects with competent aortic
      and tricuspid valves. The length of the incision ranged from 4 to 6 cm, was away
      from the mammary gland, and remained entirely covered by the adducted arm. All
      children recovered right shoulder function within days, and cosmetic results were
      very satisfying. One patient developed iliac artery stenosis following inguinal
      artery cannulation. CONCLUSION: Closure of perimembranous VSDs in older children
      can be safely performed through a right axillary thoracotomy without compromising
      the accuracy of the repair. The cosmetic results are excellent.

PMID- 17012112
TI  - Kirschner wire migration from the right sternoclavicular joint to the heart: a
      case report.
AB  - Presented here is a rare case in which Kirschner wires migrated from the right
      sternoclavicular joint to the heart. A 29-year-old man suffering from
      sternoclavicular instability due to a motorcycle accident received surgical
      fixation with Kirschner wires. Six months after the surgery, the chest x-ray
      showed migration of the 3 broken wires to the anterior mediastinum and to the
      right hemithorax. The patient was asymptomatic and was scheduled for elective
      surgical extraction of the migrating wires because of the potential danger of
      injuring the mediastinal organs.During the surgery, the intracardiac location of
      all wires was discovered,and the wires were successfully extracted from the
      extracorporeal circulation. This rare and potentially lethal complication is
      discussed.

PMID- 17012113
TI  - Permeability and retention studies of (-)epicatechin gel formulations in human
      cadaver skin.
AB  - (-)Epicatechin (EC) is a major antioxidant component of grape seed extract which
      has become increasingly popular in topical skin preparations. This study assessed
      the following: (1) the permeability through cellulose membranes of EC in three
      different gel formulations (Carbopol 940, Klucel, and Ultrez 10); (2) the effect
      of three different antioxidants (butylated hydroxytoluene (BHT), alpha-tocopherol
      (VE), and ascorbic acid (AA)) on the stability and penetration properties of EC;
      and (3) the permeability and retention of EC in Ultrez 10 gels, supplemented with
      BHT or VE, on human cadaver skin. Permeability studies through cellulose
      membranes showed that different gelling agents do not significantly affect the
      permeability of EC (n = 7/gel; p > 0.05). BHT and VE have antioxidant properties
      superior to AA (p < 0.05) and preserve 100% of the initial content of EC for 28
      days. Permeation studies on cadaver human skin, following application of two
      anhydrous gel formulations (0.5% EC in Ultrez 10 containing BHT or VE), showed
      that EC was not detectable in the receiving solution. However, the EC amount in
      viable skin increased with time, indicating that EC penetrated and was retained
      in the upper part of the skin for approximately 1% and 3% of the dose for the
      formulations containing BHT and VE, respectively.

PMID- 17012114
TI  - Interconversion kinetic studies of betamethasone acetate polymorphs in water.
AB  - This study assessed the effect of polymers on the transformation of polymorphs of
      betamethasone acetate (BA) when suspended in water. The results showed that the
      polymers, in particular HPMC E5, retarded the transition of the forms Ialpha and
      Ibeta. However, the form Ialpha, as the metastable form, with the aid of HPMC E5,
      was preferred for BA suspension preparation through kinetic studies, while the
      form Ibeta was not suitable due to its instability in water.

PMID- 17012115
TI  - Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D
      optimal design and the desirability function.
AB  - D-optimal design and the desirability function were applied to optimize a self
      microemulsifying drug delivery system (SMEDDS). The optimized key parameters were
      the following: 1) particle size of the dispersed emulsion, 2) solubility of the
      drug in the vehicle, and 3) the vehicle compatibility with the hard gelatin
      capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil
      mixture, were included in the experimental design. The results of the
      mathematical analysis of the data demonstrated significant interactions among the
      formulation variables, and the desirability function was demonstrated to be a
      powerful tool to predict the optimal formulation for the explored system.

PMID- 17012116
TI  - Spray pattern analysis for metered dose inhalers I: Orifice size, particle size,
      and droplet motion correlations.
AB  - Factors that influence spray pattern measurements of pressurized, metered-dose
      inhalers have been evaluated. Spray patterns were correlated with changes in
      actuator orifice diameter, particle size profiles, and calculated estimates of
      particle-size dynamics of plumes during a spray. Spray patterns, regardless of
      actuator orifice size, were ellipsoid in the vertical direction. Measures of
      elliptical ratio, major axis, and minor axis were significantly influenced by
      orifice size in a non-linear fashion over the range of orifice sizes
      investigated. Spray patterns also correlated with particle size profile and spray
      geometry measurements. Spray distribution asymmetry may be related to droplet
      evaporation and sedimentation processes. However, the spray patterns did not
      appear sensitive to changes in gravitational force acting on the plume. Instead,
      it is postulated that elliptical spray patterns may have dependence on fluid
      dynamic processes within the inhaler actuator. Developing an understanding of
      these processes may provide a basis for developing spray pattern tests with
      relevance to product performance.

PMID- 17012117
TI  - Solubility and dissolution rate of progesterone-cyclodextrin-polymer systems.
AB  - This contribution focused on the solubility improvement of the poorly water
      soluble steroid hormone progesterone which, in its natural state, presents a
      reduced oral bioavailability. In the first part of this study, two simple,
      reproducible methods that were candidates for use in the preparation of inclusion
      complexes with cyclodextrins were investigated. Solubility capacities of the
      progesterone complex with hydroxypropyl-beta-CD (HPbeta-CD), hydoxypropyl-gamma
      CD (HPgamma-CD), permethyl-beta-CD (PMbeta-CD), and sulfobutylether-beta-CD
      (SBEbeta-CD), prepared by the freeze-drying and precipitation methods, were
      evaluated by Higuchi phase solubility studies. The results showed that HPbeta-CD
      and PMbeta-CD were the most efficient among the four cyclodextrins for the
      solubilization of progesterone, with the highest apparent stability constants.
      Therefore, dissolution studies were conducted on these latest
      progesterone/cyclodextrin complexes and physical mixtures. Two additional natural
      cyclodextrins, beta-CD and gamma-CD, were taken as references. Hence, the
      influence of more highly soluble derivatives of beta-CD (HPbeta-CD, PMbeta-CD) on
      the progesterone dissolution rate, in comparison to pristine beta-CD, alongside
      an increase in the cavity width for gamma-CD versus beta-CD, were investigated.
      The dissolution kinetics of progesterone dissolved from HPbeta-CD, PMbeta-CD, and
      gamma-CD revealed higher constant rates in comparison to beta-CD. Therefore, the
      aim of the second part of this study was to investigate the possibility of
      improving the dissolution rate of progesterone/beta-CD binary systems upon
      formation of ternary complexes with the hydrophilic polymer, PEG 6000, as beta-CD
      had the smallest progesterone solubility and dissolution capacity among the four
      cyclodextrins studied (beta-CD, HPbeta-CD, HPgamma-CD and PMbeta-CD). The results
      indicated that dissolution constant rates were considerably enhanced for the 5%
      and 10% progesterone/beta-CD complexes in PEG 6000. The interaction of
      progesterone with the cyclodextrins of interest on the form of the binary
      physical mixtures, complexes, or ternary complexes were investigated by
      differential scanning calorimetry (DSC) and Fourier transformed-infrared
      spectroscopy (FT-IR). The results proved that progesterone was diffused into the
      cyclodextrin cavity, replacing the water molecules and, in case of ternary
      systems, that the progesterone beta-cyclodextrin was well dispersed into PEG,
      thus improving progesterone bioavailability for subsequent oral delivery in the
      same way as derivatized cyclodextrins. The present work proves that ternary
      complexes are promising systems for drug encapsulation.

PMID- 17012118
TI  - Influence of tartaric acid on the bioadhesion and mechanical properties of hot
      melt extruded hydroxypropyl cellulose films for the human nail.
AB  - The objective of this study was to investigate the influence of tartaric acid
      (TTA) on the bioadhesive, moisture sorption, and mechanical properties of hot
      melt-extruded (HME) hydroxypropyl cellulose (HPC) films containing polymer
      additives. Two Klucel EF and LF batches (HPC, MW: 80000 and 95000, respectively)
      containing the model antifungal drug ketoconazole (one batch of each MW with and
      without TTA 4%) were prepared into films by HME using a Killion extruder (Model
      KLB-100). The bioadhesive properties of the HPC films, with and without TTA, were
      investigated ex vivo on the human nails. The parameters measured were work of
      adhesion and peak adhesion force (PAF). A statistically significant increase in
      both the area under the curve (AUC) and PAF was seen for the HME films containing
      TTA than those without TTA. Moisture content of hot-melt extruded HPC films was
      determined using thermogravimetric analysis (TGA). TGA data collected at the two
      week interval (25 degrees C/60% RH), measured higher moisture content for the TTA
      containing films than those without TTA. Tensile strength and percent elongation
      were determined utilizing a TA.XT2i Texture Analyzer(R) equipped with a 50-kg
      load cell, TA-96 grips, and Texture Expert software. TTA functioned as an
      effective plasticizer, increasing percent elongation and decreasing tensile
      strength of the HPC films. TTA could potentially be a candidate for transnail
      applications in film devices prepared by hot-melt extrusion technology.

PMID- 17012119
TI  - Evaluation of the performance of a new continuous spheronizer.
AB  - This study aims to evaluate the performance of a new continuous spheronizer with
      multiple concentric chambers. The characteristics of the pellets produced in the
      different chambers (moisture content, mechanical strength, density, sphericity,
      size, release of a drug) were compared by multivariate analysis of variance
      (MANOVA), when different times of spheronization and chambers were considered.
      The statistical analysis has shown that both the diameter of the chambers and the
      time of spheronization affected the properties of the pellets, and, thus, they
      must be considered when the spheronizer is used. To minimize these effects all
      the forming pellets should be processed in all chambers for a defined period of
      time.

PMID- 17012120
TI  - Effect of chitosan-coated alginate microspheres on the permeability of Caco-2
      cell monolayers.
AB  - Alginate microspheres were prepared by emulsification/internal gelation and
      coated with chitosan. The ability of chitosan-coated alginate microspheres to
      increase the paracellular transport across Caco-2 cell monolayers was evaluated
      in comparison to uncoated microspheres and chitosan solutions. Transport studies
      were performed by using a permeability marker, Lucifer Yellow (LY), and by
      measuring the transepithelial electric resistance (TEER) variations. Furthermore,
      the occurrence of cytotoxic effects was assessed by evaluating neutral red uptake
      in viable cells and lactate dehydrogenase (LDH) release from damaged cells. A 3
      fold increase on LY permeability was obtained for coated microspheres when
      compared to chitosan solutions. TEER variations were in agreement with
      permeability results. Chitosan solutions exhibited a dose-dependent toxicity, but
      coated microspheres did not decrease the viability of cells. Chitosan-coated
      alginate microspheres have potential to be used as carriers of poorly absorbable
      hydrophilic drugs to the intestinal epithelia and possibly increase their oral
      bioavailability.

PMID- 17012121
TI  - Paclitaxel-loaded lipid nanoparticles prepared by solvent injection or ultrasound
      emulsification.
AB  - Lipid nanoparticles were fabricated as an injectable carrier system for
      paclitaxel. The components for the lipid matrix were based on phospholipids, and
      sucrose fatty acid ester was used as an emulsifier. Formulation prepared with
      solvent injection has a slightly larger particle size (187.6 nm) than the
      formulation (147.7 nm) prepared with ultrasound emulsification. Differential
      scanning calorimetry results indicated that paclitaxel entrapped in the lipid
      nanoparticles existed in an amorphous state in the lipid matrix. In vitro drug
      release was rather slow; only 12.5-16.5% of the drug released from the
      formulations within 14 days. Lipid nanoparticles demonstrated their potential as
      a promising pharmaceutical formulation of paclitaxel.

PMID- 17012122
TI  - Solid-phase extraction and HPLC analysis of methylparaben and propylparaben in a
      concentrated antibiotic suspension.
AB  - An accurate and precise solid-phase extraction coupled with high performance
      liquid chromatography (SPE/HPLC) method developed for the quantification of
      antimicrobial preservatives (methylparaben and propylparaben) in oxytetracycline
      injectable suspension is described in this article. The SPE technique was
      necessary to quantify the preservatives since the high concentration of the drug
      and excipients was masking low levels of preservatives, making quantification
      difficult. This developed HPLC method was stability-indicating and found to be
      linear between 1.3 to 2.4 mg/mL for methylparaben and 0.15 to 0.27 mg/mL for
      propylparaben in this concentrated antibiotic suspension formulation. The
      extraction recoveries were 98.8-101.6%. System precision and sample extraction
      precision (RSD) were less than 1%.

PMID- 17012123
TI  - The influence of formulation on the dissolution profile of diclofenac sodium
      tablets.
AB  - In attempts to design delayed-release tablets of diclofenac sodium, seven
      experimental batches were produced. The influence of super-disintegrant
      croscarmellose sodium (CCS), the granulation process, and the thickness of
      Eudragit L 100 coating film were evaluated. The values of dissolution efficiency
      and the similarity factor were used to compare the dissolution profiles of each
      experimental batch and the reference Voltaren. Both methods appear to be
      applicable and useful in comparing dissolution profiles. Based on such values
      four batches were considered similar when contrasted with the reference. The
      results suggest an optimal relationship between the amount of CCS and the
      thickness of the coating film, which provides appropriate dissolution rate of
      diclofenac sodium from the dosage forms.

PMID- 17012126
TI  - The importance of analytical quality specifications for biomarker assays
      currently used in acute cardiac care.
AB  - It is very important that cardiac biomarkers on which clinically relevant
      decisions will rest are measured with highly reliable assays. Adequate studies
      are needed before new methods can be implemented in the laboratory routine, and
      only well-documented assays should be considered for clinical use. Therefore, it
      is critical that, as new biomarkers are proposed, quality specifications are
      developed. Only after appropriate analytical quality specifications are
      addressed, the issues pertaining to methodological differences that result in non
      harmonized concentration values, and clinical interpretation of biomarker
      concentrations will be reconciled. Today, the technology to address many analytic
      problems is at hand, but commitment on the part of manufacturers and their
      customers in the laboratory and clinical communities is essential. The design
      control loop is not closed until the finished in vitro diagnostic system is
      adequately validated to meet the customer needs, including analytical quality
      specifications. It is essential to determine the attributes and performance
      characteristics of relevant competitive systems and their degree of acceptance by
      clinical laboratories in order to demonstrate that user needs are definitely met.
      The responsibility of defining and implementing these issues must be a shared
      responsibility among laboratorians, clinicians, industry, and regulatory agencies
      on an international front. To date, two sets of quality specifications have been
      published, one for cardiac troponin assays and one for B-type natriuretic peptide
      assays. Both address analytical factors, such as calibrator characterization,
      antibody specificity, assay sensitivity and imprecision, and interferents, as
      well as preanalytical factors, such as sample type and stability. It would be
      ideal if regulatory agencies, such as FDA in the United States, accept these
      criteria for premarket approval clearance applications.

PMID- 17012127
TI  - Anchor wire technique improves device deliverability during PCI of CTOs and other
      complex subsets.
AB  - INTRODUCTION: The DES era has increased the demand on PCI-based revascularization
      and lesion complexity. One of the technical problems still limiting success rates
      in complex PCI is limited device deliverability. This work describes a new
      technique to improve deliverability. METHODS: When deliverability was limited
      during PCI, a second 0.014-inch guide wire was inserted into the non-target
      artery. Then, another attempt was made to deliver the device to the target
      lesion. RESULTS: The technique was attempted in 13 consecutive cases with
      difficulties in delivering a device; five of CTO (38.5%), five of diffuse
      calcifications (38.5%), two of direct stenting (15.3%) and one case (7.7%) of
      dilated aortic root. The anchor wire technique was the only maneuver needed in
      eight (61.5%) cases. Additional technique was needed in four (30.7%) cases. In
      four out of five (80%) CTO cases, the anchor wire technique allowed successful
      PCI and to deliver a balloon across a CTO. Final procedural success was achieved
      in 12 (92.3%) cases. CONCLUSIONS: The anchor wire technique can be very useful in
      increasing success rates in CTOs and various complex PCI's and has the advantage
      of being simple to use, without a need to re-cross the target lesion or to
      exchange PCI system.

PMID- 17012128
TI  - Prior heart failure among patients with acute coronary syndromes is associated
      with a higher incidence of in-hospital heart failure.
AB  - BACKGROUND: There are few data regarding the impact of prior heart failure (P-HF)
      on the presentation, course and outcomes of acute coronary syndromes (ACS).
      METHODS AND RESULTS: We prospectively analyzed all ACS patients admitted in all
      cardiology wards in Israel during February and March, 2004. Of the 2098 patients,
      156(7.4%) had P-HF. These patients were older (75 [66.5-81] versus 63 [53-74]
      years, (P<0.001)) and more often female (38.5% versus 25.0%, P<0.001)), with a
      higher prevalence of coronary artery disease risk factors, prior cardiac disease
      and procedures, and other co-morbidities. They more often presented with atypical
      angina and heart failure and less with ST-elevation (18.6% versus 51.3%,
      p<0.0001). In-hospital heart failure developed more frequently (15.4% versus
      6.1%, p = 0.00001), including cardiogenic shock (7.1% versus 2.9%, p = 0.005), as
      did persistent atrial fibrillation (6.4% versus 0.7%, p<0.001), but not ischemic
      complications. After adjustment for differences, P-HF was not independently
      associated with 30 day or six-month mortality, but at one-year follow-up, it was
      (OR 1.16, 95% CI 1.0-2.5). P-HF was also independently associated with increased
      incidence of heart failure upon admission or thereafter in-hospital (OR = 4.3,
      95% CI 2.8-6.6). CONCLUSIONS: P-HF ACS patients had high-risk features, lower
      incidence of ST-elevation, and higher one-year adjusted mortality. P-HF was also
      independently associated with in-hospital heart failure, suggesting they should
      be monitored vigilantly.

PMID- 17012129
TI  - Distal embolic protection during percutaneous coronary intervention in patients
      with acute coronary syndromes: the RUBY study.
AB  - OBJECTIVE: To assess the safety and feasibility of the GuardWire system as an
      embolic protection device during percutaneous coronary intervention (PCI) in
      acute coronary syndromes (ACS). BACKGROUND: Distal embolization occurs in
      approximately 15% of patients after primary angioplasty and is associated with
      reduced myocardial reperfusion, more extensive myocardial damage and a poor
      prognosis. Distal embolic protection could reduce the rate of embolic
      complications and improve outcome. METHODS: 329 patients (mean age 60+/-12 years)
      were included: 278 (84.5%) with ST-elevation myocardial infarction (STEMI), 50
      (15.2%) with unstable angina/non-STEMI and 1 (0.3%) with post-infarction angina.
      Primary endpoint was the incidence of major adverse cardiac events (MACE) at 30
      days. Secondary endpoints were the magnitude of ST-segment resolution at 90 and
      180 min post-procedure, myocardial blush grade, and angiographically visible
      distal emboli. RESULTS: The GuardWire system was successfully positioned in 99%
      of patients. Complete ST-elevation resolution (>70%) was observed in 28.5%
      immediately post-procedure, and in 35.4% and 41.6% at 90 and 180 min post
      procedure. TIMI-3 flow grade was achieved by 89.8% of patients after intervention
      and mean corrected TIMI frame count was 20.2+/-13.2. Grade-3 myocardial blush was
      seen in 47.7% of patients and distal emboli were angiographically visible in
      7.4%. Incidence of MACE at 30 days was 3.3% (death 1.2%; Q-wave MI 0.3%; non-Q
      wave MI 0.3%; coronary artery bypass graft 0.6%; repeat PCI 0.9%). CONCLUSION:
      The GuardWire system was successfully positioned in nearly all patients without
      complications. The use of this embolic protection device in ACS patients
      undergoing PCI was associated with low rates of distal embolization and 30-day
      MACE.

PMID- 17012130
TI  - Are the American College of Cardiology/Emergency Cardiac Care (ACC/ECC)
      guidelines useful in triaging patients to telemetry units?
AB  - PURPOSE: To determine if the ACC/ECC guidelines (1991) properly stratify patients
      according to risk of arrhythmia, defined as a single event on cardiac monitoring,
      and benefit, defined as a subsequent management change from a recorded telemetry
      event. SUBJECTS AND METHODS: In 2003, a prospective study of 217 consecutive
      patients admitted to a 24-bed telemetry unit was conducted for 25 days at a major
      academic hospital. Patients were categorized per ACC/ECC guidelines as
      appropriate (class I & II) or inappropriate (class III) based on a non
      cardiologist admission diagnosis. A cardiologist-led group then reclassified
      patients at the time of admission using a brief interview. Continuous telemetry
      recorded arrhythmias and resultant management changes were reviewed and recorded
      daily. Subgroup analysis of patients admitted with a chief complaint of chest
      pain was also performed. In 2004, after this trial was performed, the American
      Heart Association released a scientific statement updating practice standards for
      ECG monitor; however, this paper is based upon the original 1991 ACC/ECC
      guidelines. RESULTS: Reclassification significantly decreased the percentage of
      all class I & II patients from 91% to 71% (P<0.001) and the percentage of class I
      & II patients with chest pain from 100% to 58% (P<0.001) without increasing the
      percentage of arrhythmias occurring in class III patients. Class II patients had
      a statistically significant higher percentage of arrhythmias than class I and III
      patients before and after reclassification (P<0.001 and P<0.001, respectively).
      Management changes occurring as a direct result of telemetry events were higher
      in class II than class I or III patients before and after reclassification (P =
      0.01 and P = 0.03). Life-threatening arrhythmias (sustained ventricular
      tachycardia or ventricular fibrillation) occurred in 1% of the 216 patients
      enrolled in this study. CONCLUSIONS: (1) Cardiology input using ACC/ECC
      guidelines and a brief interview at admission safely reduced total admissions
      primarily by identifying low risk chest pain admissions inappropriate for
      inpatient telemetry monitoring. (2) Life threatening arrhythmias occurring in
      patients admitted to telemetry are rare.

PMID- 17012131
TI  - PCI of an ostial LCX stenosis, with protection of LAD, using two guiding
      catheters.
AB  - A 65-year-old male patient with unstable angina and history of hypertension,
      diabetes, and hyperlipidaemia was referred for coronary angiography. On the
      diagnostic procedure, separate ostia of LAD and LCX were found, with a
      significant lesion in the middle LAD and a high-grade ostial lesion of LCX, which
      we considered as culprit. We decided to perform an interventional procedure on
      both lesions. After positioning a guiding catheter in the LCX ostium, we wanted
      to protect the LAD, but we could not wire both arteries because of separation
      between the two ostia. We decided than to engage a second guiding catheter in the
      LAD ostium and wire the LAD. There were no difficulties in implanting safely a
      stent in the LCX ostium. After that, we proceeded with a standard intervention on
      the LAD with stent implantation.

PMID- 17012132
TI  - Spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) should be considered as a cause of
      the acute coronary syndrome in young patients with few apparent risk factors for
      coronary artery disease, in females in the peripartum period, and in patients who
      are at a higher risk for this condition. SCAD can also present as sudden death
      and cardiogenic shock. Several mechanisms have been described in the
      pathophysiology of this condition. Urgent coronary angiography is indicated if
      SCAD is suspected. Percutaneous coronary artery stenting and coronary artery
      bypass grafting are the main treatment strategies.

PMID- 17012133
TI  - Primary stenting of an unprotected left main coronary artery total occlusion in a
      patient with acute myocardial infraction and cardiogenic shock.
AB  - Acute total occlusion of the left main coronary artery (LMCA) is a rare
      angiographic finding with very poor prognosis. We report a case of a 39-year-old
      man who presented with pulmonary edema and cardiogenic shock due to an acute
      anterior myocardial infarction. Coronary angiography, which was performed under
      the support of an intra-aortic balloon pump, revealed total occlusion of the
      LMCA. Prompt and successful percutaneous transluminal coronary angioplasty with
      sirolimus-stent deployment in the LMCA allowed for an uneventful recovery and
      discharge of the patient.

PMID- 17012134
TI  - Monitoring compliance to guidelines.

PMID- 17012135
TI  - Systemic markers of inflammation--are they useful predictive tools in coronary
      artery disease?

PMID- 17012136
TI  - Quality of emergency room care for atrial fibrillation.
AB  - OBJECTIVES: Atrial fibrillation (AF) is the most common arrhythmia in emergency
      rooms (ER). We surveyed the clinical characteristics and quality of care of AF
      patients in three emergency rooms in Helsinki, Finland. DESIGN: Observational
      data of the treatment of 179 consecutive symptomatic AF patients were
      prospectively collected. The quality of care was analysed according to a
      predestined set of criteria. RESULTS: Mean age of the patients was 63 years and
      61% were men. The leading symptom was palpitation (86%). Sinus rhythm was
      achieved in 70%. New anticoagulation was initiated in 20% and cardiovascular
      medication modified in 42% of patients. Considering the overall quality of care,
      including documentation in the patient chart, it was classified as good in 53% of
      all patients, whereas the quality of therapeutic decisions and planning for
      follow-up was good in 77%. CONCLUSIONS: The ER visit results in extensive
      treatment modifications in two of three patients. Although inadequate care is
      rare, maintaining good quality requires adherence to clinical guidelines, careful
      documentation and plans for follow-up.

PMID- 17012137
TI  - Markers for endothelial dysfunction, but not markers for oxidative stress
      correlate with classical risk factors and the severity of coronary artery
      disease. (A subgroup analysis from the Ludwigshafen Risk and Cardiovascular
      Health Study).
AB  - OBJECTIVE: Endothelial dysfunction and oxidative stress are involved in
      atherogenesis. In the search for predictors of vascular disease markers for
      endothelial dysfunction and oxidative stress were analyzed. METHODS: Of 208
      consecutive patients 22% were controls (CO) without coronary artery disease
      (CAD), 52% presented with stable angina (SAP) and 26% had acute coronary
      syndromes (ACS). Nitric oxide (NO), thrombomodulin (TM), von Willebrand factor
      (vW), sVCAM-1, sICAM-1, sP-selectin, sE-selectin, sL-selectin and C-reactive
      protein (CRP) were determined as markers for endothelial dysfunction, glutathione
      (GSH), glutathione peroxidase (Gpx), myeloperoxidase (Mpx), lipid peroxides
      (Lpx), 8-isoprostane (Iso), superoxide dismutase (SOD), total antioxidant
      capacity (TAC) and homocysteine (Hc) as markers for oxidative stress. RESULTS:
      The increases of TM, vW, sVCAM-1, CRP, SOD and Mpx correlated with the CAD status
      in the order CO < SAP < ACS, whereas NO and sL-selectin were inversely correlated
      (p < 0.05, resp.). The other markers remained unchanged. For several markers a
      significant relationship to risk factors was detected. CONCLUSIONS: Markers for
      endothelial dysfunction rather than those for oxidative stress may serve as
      indicators for the presence and severity of CAD.

PMID- 17012138
TI  - Plasma-soluble CD40 is related to cholesterol metabolism in patients with
      moderate hypercholesterolemia.
AB  - OBJECTIVES: CD40 is a marker of immunological activation and is expressed in the
      atherosclerotic lesions. We studied whether CD40 and cholesterol synthesis
      pathways are associated with each other. DESIGN: Forty-three subjects were
      randomly assigned to receive either simvastatin (n = 14), atorvastatin (n = 15),
      or placebo (n = 14) for eight weeks. Plasma samples were obtained before and at
      the end of the follow-up. sCD40 levels were measured in duplicate using an enzyme
      linked immunosorbent assay. Cholesterol, its precursor lathosterol, the plant
      sterols campesterol and sitosterol as well as 27-hydroxycholesterol were
      quantified by gas-liquid chromatography-mass spectrometry. RESULTS: sCD40 was
      inversely correlated with the lathosterol to cholesterol ratio (r = - 0.47, p =
      0.002), an indicator of cholesterol synthesis rate, as well as apolipoprotein A-I
      (r = - 0.38, p = 0.01) in addition to being directly correlated with 27
      hydroxycholesterol (r = 0.40, p = 0.008). In multivariate linear regression
      analysis these three predictors explained 37% of the total variability of sCD40
      levels. Simvastatin or atorvastatin treatment had no significant effect on sCD40
      levels. CONCLUSION: These results indirectly suggest that sCD40 concentrations
      are related to cellular cholesterol levels. This may be a novel indication for
      the relationship between immunological processes and cholesterol metabolism.

PMID- 17012139
TI  - Arterial stiffness and Chlamydia pneumoniae infection in coronary artery disease.
      Is there a link?
AB  - BACKGROUND: We investigated the possible association between antichlamydial
      antibodies and pulse wave analysis (PWA) parameters in a cohort of patients with
      coronary artery disease (CAD). METHODS: The augmentation index (AI), the
      reflection time index (RTI) and the time to the beginning of the reflected wave
      (CT-1) were estimated (Sphygmocor ATCOR Medical). IgA titers >or= 40 and IgG
      >or=80 were considered as positive (microimmunofluorescence test). Patients also
      underwent coronary angiography, ultrasound carotid measurements and 24 h
      ambulatory blood pressure (BP) measurements. RESULTS: No differences existed in
      the traditional risk factors for CAD between the seronegative and seropositive
      IgA/ IgG groups. IgA seropositive subjects had higher values of AI (p < 0.01)
      comparing to seronegatives whilst the levels of CT-1 and RTI were lower (p <
      0.011 and p < 0.02 respectively). No differences in AI, CT-1 and RTI values were
      found between IgG seropositive/ seronegatives patients. CONCLUSIONS: An
      association was indicated between IgA antichlamydial titers and PWA parameters in
      patients with CAD, supporting that the connecting link between arterial stiffness
      and CAD might include this microorganism.

PMID- 17012140
TI  - Oxidative stress during coronary artery bypass operations: importance of surgical
      trauma and drug treatment.
AB  - OBJECTIVE: To investigate oxidative stress and myocardial injury at different
      stages of coronary artery bypass grafting (CABG). DESIGN: Twenty patients
      underwent CABG with use of cardiopulmonary bypass (CPB) and with intermittent
      sampling of plasma and urine. Main markers were: 8-iso-PGF2alpha (oxidative
      stress); troponin T (myocardial injury); and 15-keto-dihydro-PGF2alpha and hsCRP
      (inflammation). RESULTS: Plasma 8-iso-PGF2alpha increased after start of surgery,
      but there was no further rise during CPB or after aortic cross-clamp release and
      no significant myocardial arterio-venous differences. An increase in troponin T
      was seen early after the operation, but no relationship was established between 8
      iso-PGF2alpha and troponin T. 8-iso-PGF2alpha levels were elevated by
      preoperative withdrawal of acetylsalicylic acid (ASA) but reduced by
      intraoperative use of heparin. 15-keto-dihydro-PGF2alpha was elevated during
      operation and hsCRP following operation. CONCLUSIONS: In the present study
      oxidative stress was multifactorial in origin with main impacts from surgical
      trauma, less from CPB and little if any from myocardial ischemia-reperfusion
      events. In addition, cardiovascular drugs in common use like ASA and heparin
      seemed to influence the pro- and antioxidant balance, a finding that has to be
      confirmed in future studies.

PMID- 17012141
TI  - Cardioprotective effect of pretreatment with beta-glucan in coronary artery
      bypass grafting.
AB  - BACKGROUND: Beta-glucan pretreatment has been shown to attenuate inflammatory
      response and to protect against ischemia-reperfusion injury in animal studies.
      The aims of the present study were to examine the safety of pretreatment with
      beta-1,3/1,6-glucan in patients scheduled for coronary artery bypass grafting
      (CABG), and to investigate whether beta-1,3/1,6-glucan pretreatment could
      suppress inflammatory response and protect against ischemia-reperfusion injury
      following CABG. METHODS: Twenty one patients scheduled for CABG were assigned to
      oral beta-1,3/1,6-glucan 700 mg (Group 1) or 1 400 mg (Group 2) five consecutive
      days before surgery and were compared with a control group (Group 3). Blood
      samples were drawn preoperatively and on the first, third and fifth postoperative
      day for analysis of acute-phase reactants, hematology, cytokines and myocardial
      enzymes. RESULTS: The study drug was well tolerated. Creatine kinase isoenzyme MB
      was significantly lower in Group 2 compared with controls on the first
      postoperative day (p = 0.028). Mean change in cardiac troponin T was lower in
      Group 2 compared with controls (p = 0.028). CONCLUSIONS: Beta-1,3/1,6-glucan
      pretreatment is safe in patients undergoing CABG and may protect against ischemia
      reperfusion injury following CABG.

PMID- 17012142
TI  - What is a normal lactate level during cardiopulmonary bypass?
AB  - Blood lactate levels during cardiopulmonary bypass are often used to verify
      adequacy of perfusion. The present investigation aimed to propose a threshold for
      hyperlactatemia. Blood lactate levels in 5 121 cardiac surgical patients were
      retrospectively analysed by a review of database records. Hyperlactatemia was
      defined as a value equal to the 90th percentile of the identified lactate
      distribution at weaning from cardiopulmonary bypass. Patient demographics,
      background and outcome statistics were performed stratified on presence of
      hyperlactatemia. The threshold for hyperlactatemia was found to equal 2 mmol/l.
      Significant predictors of hyperlactatemia based on logistic regression modelling
      were age, complex surgery, duration of cardiopulmonary bypass, blood transfusion,
      acid base level, emergency operations, diabetes, vasoactive intervention, venous
      blood-return to the heart-lung machine and renal function. Patients with
      hyperlactatemia required longer intensive care and postoperative ventilatory
      support. Complications were more frequent, especially: renal dysfunction,
      infections, respiratory and circulatory disorders. Hospital mortality was 13.3%
      compared to an overall level at 2.2%. The threshold for hyperlactatemia during
      cardiopulmonary bypass attained 2 mmol/l and predicted increased morbidity and
      mortality.

PMID- 17012143
TI  - Limb ischemic postconditioning protects myocardium from ischemia-reperfusion
      injury.
AB  - OBJECTIVE: To test the hypothesis that limb ischemic postconditioning protects
      the myocardium from reperfusion injury, and examine the mechanism involved.
      DESIGN: Forty rabbits were randomly divided into four groups: Control, Ischemic
      Preconditioning, Ischemic Postconditioning and Remote Postconditioning.
      Myocardial infarct size and tissue myeloperoxidase activity were determined at
      the end of the experiment. Plasma creatine kinase and malondialdehyde activity
      were measured at baseline, the end of ischemia, and after 3 h of reperfusion
      respectively. RESULTS: Myocardial infarct size was significantly reduced in
      Ischemic Preconditioning, Ischemic Postconditioning and Remote Postconditioning
      as compared to Control (p < 0.01). Results were confirmed by plasma creatine
      kinase activity. Plasma malondialdehyde was significantly less at 3 h of
      reperfusion in Ischemic Preconditioning, Ischemic Postconditioning and Remote
      Postconditioning than that in Control (p < 0.01). Neutrophil accumulation
      (myeloperoxidase activity) in the area at risk was less in Ischemic
      Preconditioning, Ischemic Postconditioning and Remote Postconditioning than that
      in Control (p < 0.01). CONCLUSION: Remote postconditioning reduces myocardial
      infarction in rabbits. The mechanism involved might be reduced oxygen radical
      induced injury and improved antioxidant action.

PMID- 17012144
TI  - Relationships between nitric oxide-mediated endothelial function, eNOS coupling
      and blood pressure revealed by eNOS-GTP cyclohydrolase 1 double transgenic mice.
AB  - Endothelium-dependent relaxation in conduit vessels is mediated largely by nitric
      oxide (NO), produced by the enzyme endothelial nitric oxide synthase (eNOS) in
      the presence of the cofactor tetrahydrobiopterin (BH4) and mediated through a
      cGMP-dependent downstream signalling cascade. Endothelial NOS regulates blood
      pressure in vivo, and impaired endothelial NO bioactivity in vascular disease
      states may contribute to systemic hypertension. In the absence of sufficient
      levels of the cofactor BH4, NO becomes uncoupled from arginine oxidation and eNOS
      produces superoxide rather than NO. The enzymatic uncoupling of eNOS is an
      important feature of vascular disease states associated with increased oxidative
      stress. However, whether eNOS coupling, rather than overall eNOS activity, has
      specific effects on endothelium-dependent vasorelaxation in vitro, or on blood
      pressure regulation in vivo, remains unclear. In this study, we evaluate the
      relationships between blood pressure and endothelial function in models of eNOS
      uncoupling, using mice with endothelium-targeted transgenic eNOS overexpression
      (eNOS-Tg), in comparison with littermates in which eNOS coupling was rescued by
      additional endothelium-targeted overexpression of GTP cyclohydrolase 1 (eNOS/GCH
      Tg) to increase endothelial BH4 levels. Despite the previously characterized
      differences in eNOS-dependent superoxide production between these animals, we
      find that blood pressure is equally reduced in both genotypes, compared with wild
      type animals. Furthermore, both eNOS-Tg and eNOS/GCH-Tg mice exhibit similarly
      impaired endothelium-dependent vasorelaxation. We show that reduced
      vasorelaxation responses result from desensitization of cGMP-mediated signalling
      and are associated with increased NO production rather than changes in superoxide
      production.

PMID- 17012145
TI  - Paraventricular nucleus influence on renal sympathetic activity in vasopressin
      gene-deleted rats.
AB  - In Wistar rats, an increase in renal sympathetic activity is induced by
      activation of presympathetic neurones in the paraventricular nucleus (PVN) and
      reflexly by a mild venous haemorrhage. Both stimuli are dependent on the release
      of vasopressin and glutamate at spinal synapses. The significance of the
      supraspinal pathway and the co-operative interaction of vasopressin with an
      excitatory amino acid is unclear. The present study examines this in Brattleboro
      rats, which have a natural vasopressin gene deletion. The responses were compared
      with Long-Evans rats, from which Brattleboro rats are derived. All rats were
      anaesthetized with a mixture of urethane (650 mg kg(-1) i.v.) and chloralose (50
      mg kg(-1) i.v.). Recordings were made of blood pressure, heart rate and renal
      sympathetic nerve activity (RSNA). Microinjection of d,l-homocysteic acid (DLH,
      0.2 m, 100 nl) at sites restricted to the PVN elicited significant increases in
      RSNA (P < 0.001) in both strains of rats. These changes were significantly
      reduced (P < 0.01) in Long-Evans rats by intrathecal application to the spinal
      cord of either a V(1a) antagonist or a glutamate antagonist (kynurenic acid),
      whereas in Brattleboro rats the changes were significantly reduced (P < 0.05)
      only by kynurenic acid. Removal of 1 ml of venous blood in Long-Evans rats
      increased RSNA by 28 +/- 4% (P < 0.01), which was significantly reduced (P <
      0.05) by prior intrathecal application of either the V(1a) antagonist or by
      kynurenic acid. The same test in Brattleboro rats caused a significantly greater
      (P < 0.05) increase (63 +/- 14.7%) in RSNA which, in contrast to Long-Evans rats,
      was unchanged by intrathecal application of the V(1a) antagonist, being
      significantly reduced (P < 0.01) only by intrathecal kynurenic acid. Thus, in
      Brattleboro rats, the lack of vasopressin in the brain sympathetic pathways
      appears to be compensated, acutely, by glutamate-releasing pathways. This might
      indicate that, in normal rats, vasopressin is more important in maintaining
      longer term adjustments to stressors.

PMID- 17012146
TI  - Prior sustained hypoxia attenuates interaction between hypoxia and exercise as
      ventilatory stimuli in humans.
AB  - Both exercise and hypoxia increase pulmonary ventilation. However, the combined
      effects of the two stimuli are more than additive, such that exercise may be
      considered to potentiate the acute ventilatory response to hypoxia (AHVR), and
      vice versa. Exposure to sustained hypoxia of 8 h duration or more has been shown
      to increase the acute chemoreflex responses to hypoxia and hypercapnia. The
      purpose of this study was to determine whether sustained exposure to hypoxia also
      changed the stimulus interaction between the effects of exercise and hypoxia on
      ventilation. Ten subjects undertook two main protocols on two separate days. On
      one day, subjects were exposed to isocapnic hypoxia (IH) at an end-tidal partial
      pressure of O(2) of 55 mmHg and on the other day, subjects were exposed to air as
      a control (C). Before and after each exposure, the sensitivity of AHVR was
      assessed during both resting conditions and exercise at 35% of the subjects'
      maximal oxygen uptake capacity. Average values (means +/- s.d.) obtained for the
      sensitivity of AHVR from protocol IH were 0.85 +/- 0.35 (rest, prehypoxic
      exposure), 1.60 +/- 0.66 (exercise, prehypoxic exposure), 1.69 +/- 0.63 (rest,
      posthypoxic exposure) and 1.81 +/- 0.86 l min(-1) %(-1) (exercise, posthypoxic
      exposure). A non-dimensional variable, Phi, was used to quantify the interaction
      present between exercise and hypoxia. The variable Phi fell significantly
      following the sustained exposure to hypoxia (P < 0.02, ANOVA), indicating that
      the degree of stimulus interaction between acute hypoxia and exercise had
      declined. We suggest that the mechanisms by which sustained hypoxia modifies
      peripheral chemoreflex function may also modify the effects of exercise on the
      peripheral chemoreflex.

PMID- 17012147
TI  - Colorectal cancer screening: do we practice what we preach?
AB  - OBJECTIVE: Compliance rates for colorectal cancer screening have been reported as
      low, and ignorance is the most common factor sighted to explain this. The aim of
      this study was to determine screening compliance among colorectal surgeons
      assumed to be educated of the risks of colorectal cancer. METHODS: A postal
      survey was distributed to the members of the American Society of Colon and Rectal
      Surgeons. RESULTS: A total of 1195 members were surveyed. All respondents
      indicated that they advocate screening. Colonoscopy every 10 years and annual
      fecal occult blood testing were the most common strategies advocated to
      individuals with baseline risk. Colonoscopy every 5 years and annual fecal occult
      blood testing were the most common strategies advocated to patients with a first
      degree relative with polyps or cancer. Most of these colorectal surgeons
      initiated their screening before 50 years of age. CONCLUSION: Colorectal cancer
      screening compliance is high among members of the American Society of Colon and
      Rectal Surgeons. These rates may be the result of awareness of the risks of
      colorectal cancer.

PMID- 17012148
TI  - A primer on natural orifice transluminal endoscopic surgery: building a new
      paradigm.
AB  - Access to the abdominal cavity is required for diagnostic and therapeutic
      endeavors for a variety of medical and surgical diseases. Historically, abdominal
      access has required a formal laparotomy to provide adequate exposure. Natural
      orifice transluminal endoscopic surgery (NOTES) is an emerging experimental
      alternative to conventional surgery that eliminates abdominal incisions and
      incision-related complications by combining endoscopic and laparoscopic
      techniques to diagnose and treat abdominal pathology. During NOTES, commercially
      available flexible video endoscopes are used to create a controlled transvisceral
      incision via natural orifice access to enter the peritoneal cavity. Common
      incision-related complications such as wound infections, incisional hernias,
      postoperative pain, aesthetic disdain, and adhesions could be minimized or
      eliminated by NOTES. NOTES has evolved from more than 2 centuries of
      technological innovations and continued growth in the field of surgical
      endoscopy. Innovative surgical endoscopists have slowly developed means to
      surpass the constraints of the gastrointestinal lumen by using a flexible
      endoscope. The future of surgical endoscopy may be the shared entity of NOTES,
      which further integrates endoscopy, gastroenterology, and minimally invasive and
      general surgery. Although the promise of NOTES is electrifying to surgeons and
      endoscopists, several key issues need to be characterized prior to the
      incorporation of NOTES into routine practice. This article reviews the status,
      contemporary body of literature, limitations, and potential future implications
      accompanying the development of NOTES.

PMID- 17012149
TI  - Laparoscopic distal pancreatectomy with splenic preservation for serous
      cystadenoma: a case report and literature review.
AB  - A minimally invasive approach can be beneficial in a spleen-preserving distal
      pancreatectomy. This article reports a 71-year-old woman who presented to her
      internist with hypertension and persistent hypokalemia. A computed tomography
      scan to rule out a functional adrenal mass incidentally revealed a 4 cm x 3 cm x
      2 cm serous cystadenoma of the distal pancreas and normal adrenal glands. The
      patient was referred to the general surgery service for resection of the distal
      pancreatic lesion. A laparoscopic spleen-preserving distal pancreatectomy was
      performed. The lesion was completely excised, and the pathology revealed serous
      cystadenoma with focal fibrosis and atrophic acini. The postoperative advantages
      of this approach were the early return of bowel function, minimal narcotic
      requirements, and early resumption of normal activities. This case illustrates
      the advantages of minimally invasive surgery in the performance of a spleen
      preserving distal pancreatectomy.

PMID- 17012150
TI  - The effect of octreotide on pancreatic damage in TNBS-induced colitis.
AB  - Inflammatory bowel disease, a chronic condition of the intestine, is associated
      with numerous extraintestinal manifestations, including pancreatitis. This study
      investigated the effect of octreotide administration on oxidative damage in a rat
      model of colitis induced by 2,4,6-trini-trobenzene sulfonic (TNBS) acid. Colonic
      and pancreatic malondialdehyde and glutathione levels are indicators of oxidative
      damage, and TNBS-induced colitis significantly increased the colonic and
      pancreatic malondialdehyde levels and decreased glutathione levels. Octreotide
      treatment was associated with decreased malondialdehyde levels and increased
      glutathione levels in the colonic and pancreatic tissue. The colonic mucosal
      structure was preserved and pancreatic inflammation decreased in rats treated
      with octreotide. Octreotide also significantly decreased nuclear factor-kB
      expression by immunohisto-chemistry in the colonic and pancreatic tissue compared
      with TNBS-induced colitis group. Octreotide appears to have protective effects
      against TNBS-induced colonic and pancreatic damage. These results imply the
      reduction in mucosal damage owing to the anti-inflammatory and antioxidant
      effects of octreotide.

PMID- 17012151
TI  - Laparoscopic expertise increases hospital volume of adrenal surgery.
AB  - The laparoscopic approach is preferred for most adrenal tumors but technical
      challenges limit its use. We evaluated the effects of the availability of
      laparoscopic expertise on the volume of the adrenal surgery at a tertiary care
      hospital. Patients undergoing adrenalectomy 5 years before and 5 years after an
      advanced laparoscopic program was established were retrospectively reviewed. The
      average annual volume increased from 2 cases during the first period to 15 cases
      during the 5 years (1999-2003) after laparoscopic expertise became available. The
      average distance of travel to the hospital was significantly greater for the
      latter patients and significantly more patients were referred from outside of a
      30-mile radius. Although the average statewide annual number of adrenalectomies
      has not significantly changed, the proportion of adrenalectomies performed at our
      institution rose. Offering a laparoscopic approach has altered physicians'
      referral patterns and has significantly increased the volume of adrenal surgery
      at the institution.

PMID- 17012152
TI  - A novel method of assessing clinical reasoning in surgical residents.
AB  - At present, surgical educators can readily assess knowledge with multiple-choice
      examinations, and inanimate models can be used to assess technical skills.
      Clinical judgment and reasoning are indispensable skills used by expert surgeons
      to solve ill-defined problems encountered in the emergency department, clinic,
      and operating room. The Script Concordance Test, a new tool of clinical reasoning
      assessment, can test the elaborated networks of knowledge that experienced
      surgeons develop over the years. It allows for multiple different approaches to
      the same problem and could be developed as both a formative and summative
      assessment tool in general surgery residency programs. This article explores the
      theoretical and practical aspects of the Script Concordance Test.

PMID- 17012153
TI  - Centers of excellence: a new dimension in surgical education.
AB  - Surgical education has always been challenging and is being made more difficult
      with the changes in the surgical environment. In the past decade, the number of
      patients available for educational purposes has decreased because of the
      development of technology that has significantly reduced their time of stay in
      the hospital and has also moved many surgical procedures to ambulatory services.
      Technologic advances also create the demand for more specialized training. The
      increased number of undergraduate, postgraduate students, and clinical fellows
      has also affected the educational mandate of the academic hospitals. Alternative
      ways to teach medicine, and especially surgery, are becoming inevitable. One such
      method is to teach students outside the operating room in a simulated
      environment. This article reports on the developments of surgical education
      centers and provides guidance for those who might wish to develop such
      educational facilities. For further information, visit www.cesei.org.

PMID- 17012154
TI  - Advanced visualization platform for surgical operating room coordination:
      distributed video board system.
AB  - One of the major challenges for day-of-surgery operating room coordination is
      accurate and timely situation awareness. Distributed and secure real-time status
      information is key to addressing these challenges. This article reports on the
      design and implementation of a passive status monitoring system in a 19-room
      surgical suite of a major academic medical center. Key design requirements
      considered included integrated real-time operating room status display, access
      control, security, and network impact. The system used live operating room video
      images and patient vital signs obtained through monitors to automatically update
      events and operating room status. Images were presented on a "need-to-know"
      basis, and access was controlled by identification badge authorization. The
      system delivered reliable real-time operating room images and status with
      acceptable network impact. Operating room status was visualized at 4 separate
      locations and was used continuously by clinicians and operating room service
      providers to coordinate operating room activities.

PMID- 17012155
TI  - Fundamentals of service lines and the necessity of physician leaders.
AB  - In the demanding and unpredictable environment of the health care industry,
      hospitals and health systems continue to search for ways to improve the
      efficiency and quality of care provision and, thus, thrive. Service line
      organization in health care, a concept that was popularized in the past, has
      recently experienced a resurgence, spanning the gamut from small community
      hospitals to large academic medical centers. The modern service line has
      transformed into an organizational tool that provides hospitals and health
      systems with a novel approach to achieve the goals of efficient and effective
      care. Physician leaders can play an integral role in the management of service
      lines, using a combination of management skills and clinical expertise to provide
      the oversight and direction necessary for assuring excellence in clinical care
      and value in its delivery. This article presents an overview of service line
      structure, implementation, implications, and the role of the physician-leader.

PMID- 17012156
TI  - Endoluminal instrumentation is changing gastrointestinal surgery.
AB  - Advances in endoluminal instrumentation and technology are enabling endoscopists
      to perform increasingly sophisticated procedures. Indications for these
      procedures are likely to expand as outcomes studies show they are efficacious and
      cost-effective. This article highlights several recent advances in endoluminal
      suturing, dissecting, and ligating and discusses the impact of these advances on
      the practice of gastrointestinal surgery. Endoluminal suturing offers select
      patients with gastroesophageal reflux disease a safe and effective alternative to
      laparoscopic surgery. Devices designed for endoluminal hemostasis and endoscopic
      mucosal resection can be used effectively for a broader range of applications and
      are already being used to perform transluminal surgery in animal models; human
      trials are forthcoming. Gastrointestinal surgeons should support efforts to
      critically evaluate endoluminal techniques because they have an opportunity to
      improve care. Surgical residents planning careers in gastrointestinal surgery
      need to understand endoscopic techniques and consider their training
      opportunities.

PMID- 17012157
TI  - No place to hide: the ethics of disclosure.

PMID- 17012158
TI  - Rapid aerosol transmission of Salmonella among turkeys in a simulated holding
      shed environment.
AB  - Once turkeys arrive at Midwest processing plants, they are usually held in large
      open-sided sheds for 1 to 4 h, waiting to be unloaded. In hot, humid weather,
      large fans are used to cool the birds. The resultant air currents distribute a
      significant amount of dust to the turkeys. The dust created in this environment
      could be a factor in the number of Salmonella-contaminated turkeys entering
      slaughter plants. The objective of this study was to determine if rapid
      transmission of Salmonella in turkeys could occur from exposure to Salmonella
      contaminated dust similar to what may be experienced in holding sheds or in other
      high-dust environments prior to slaughter. In the first experiment, trials of 3
      different concentrations of Salmonella (1.2 x 10(9), 2.6 x 10(7), and 2.6 x 10(5)
      cfu/g) were conducted to determine if transmission of Salmonella enterica serovar
      Typhimurium var. typhimurium(chi)4232 to turkeys 2 to 4 h after aerosol exposure
      to contaminated feces is possible. Results showed that turkeys became infected
      after 2 h of exposure to airborne-contaminated feces with a concentration level
      of 2.6 x 10(5) cfu of Salmonella Typhimurium/g. In the second experiment,
      consisting of 3 trials, 1 bank (5 cages wide and 3 cages high) of turkeys (n = 15
      birds per trial) was exposed to another bank of cages of S. Typhimurium
      inoculated (n = 15) birds for 2 to 4 h using a fan similar to the type in
      processing-plant cooling sheds. Results from this experiment demonstrated that
      birds could be contaminated with S. Typhimurium after 2 h of exposure. Results of
      both studies implicate contaminated dust as a route of rapid airborne
      transmission of Salmonella in turkeys. Processes that generate significant dust
      prior to slaughter should be regarded as critical control points for Salmonella.

PMID- 17012159
TI  - Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic
      traits in the chicken. I. Growth and average daily gain.
AB  - A genome scan was used to detect chromosomal regions and QTL that control
      quantitative traits of economic importance in chickens. Two unique F(2) crosses
      generated from a commercial broiler male line and 2 genetically distinct inbred
      lines (Leghorn and Fayoumi) were used to identify QTL affecting BW and daily
      average gain traits in chickens. Body weight at 2, 4, 6, and 8 wk was measured in
      the 2 F(2) crosses. Birds were genotyped for 269 microsatellite markers across
      the entire genome. Linkage distance among microsatellite markers was estimated by
      the CRIMAP program. The program QTL Express was used for QTL detection.
      Significance levels were obtained using the permutation test. For the 8 traits, a
      total of 18 and 13 significant QTL were detected at a 1% chromosome-wise
      significance level, of which 17 and 10 were significant at the 5% genome-wise
      level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively.
      Highly correlated growth traits showed similar QTL profiles within each cross but
      different QTL profiles between the 2 crosses. Most QTL for growth traits in the
      current study were detected in Gga 1, 2, 4, 7, and 14 for the broiler-Leghorn
      cross and Gga 1, 2, 4, 5, 8, and 13 for the broiler-Fayoumi cross. Potential
      candidate genes within the QTL region for growth traits at 1% chromosome-wise
      significance level were discussed. The results in the current study lay the
      foundations for fine mapping these traits in the advanced intercross lines and
      provide a start point for identification causative genes responsible for growth
      traits in chickens.

PMID- 17012160
TI  - Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic
      traits in the chicken. II. Body composition.
AB  - Two informative chicken F(2) populations based on crosses between a broiler
      breeder male line and dams from genetically distinct, highly inbred (>99%)
      chicken lines, the Leghorn G-B2 and Fayoumi M15.2, have been used for genome-wide
      linkage and QTL analysis. Phenotypic data on 12 body composition traits (breast
      muscle weight, breast muscle weight percentage, abdominal fat weight, abdominal
      fat weight percentage, heart weight, heart weight percentage, liver weight, liver
      weight percentage, spleen weight, spleen weight percentage, and drumstick weight,
      and drumstick weight percentage) were collected. Birds were genotyped for 269
      microsatellite markers across the genome. The QTL Express program was used to
      detect QTL for body composition traits. Significant levels were obtained using
      the permutation test. For the twelve traits, a total of 61 (Gga 1, 2, 3, 4, 5, 6,
      7, 8, 9, 10, 12, 15, 18, 24, and Z) and 45 (Gga 1, 2, 3, 4, 6, 7, 8, 9, 10, 12,
      15, 17, and E46) significant QTL were detected at the 5% chromosome-wise
      significance level, of which 19 and 11 were significant at the 5% genome-wise
      level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively.
      Phenotypic variation for each trait explained by all QTL across the genome ranged
      from 3.22 to 33.31% in the broiler-Leghorn cross and 4.83 to 47.12% in broiler
      Fayoumi cross. Distinct QTL profiles between the 2 crosses were observed for most
      traits. Cryptic alleles were detected for each trait. Potential candidate genes
      within the QTL region for body composition traits at the 1% chromosome-wise
      significance level were identified from databases for future association study.
      The results of the current study will increase the knowledge of genetic markers
      associated with body composition traits and aid the process of identifying
      causative genes. Knowledge of beneficial genetic variation can be incorporated in
      breeding programs to enhance genetic improvement through marker-assisted
      selection in chickens.

PMID- 17012161
TI  - Altered circulating levels of serotonin and immunological changes in laying hens
      divergently selected for feather pecking behavior.
AB  - The aim of this study was to investigate the changes in immunological parameters
      as well as changes with respect to plasma levels of serotonin and tryptophan in
      lines selected for and against feather pecking (FP) behavior [high FP (HP) line
      and low FP (LP) line] for 5 generations. The hens from the HP line had a higher
      plasma serotonin level than those from the LP line (0.059 vs. 0.037 micromol/L,
      F(2,27) = 0.031, P < 0.05). The plasma level of tryptophan was, on average, 67.30
      micromol/L and did not differ between the lines (68.3 vs. 66.3 micromol/L,
      F(2,28) = 0.36, P < 0.05). The HP line had a higher response to infectious bursal
      disease virus vaccination after 1 wk post-vaccination compared with the control
      and LP lines. The number of white blood cells (P < 0.0001) and the expression of
      MHC class I molecules on CD4 (P < 0.02), CD8beta (P < 0.006) and on B cells (P <
      0.03) were highest in the LP line compared with the control and HP lines.
      Selection for or against FP, therefore, changes the number of white blood cells
      and the expression of MHC class I molecules on T and B cells, which may influence
      the health status of the birds.

PMID- 17012162
TI  - Homocysteine remethylation in broilers fed surfeit choline or betaine and varying
      levels and sources of methionine from eight to twenty-two days of age.
AB  - Experiments were conducted to assess the effect of surfeit choline (CHOL) or
      betaine (BET) on growth performance and homocysteine (HCY) remethylation of young
      broilers fed graded levels of DL-Met (DLM) or 2-hydroxy-4-(methylthio) butanoic
      acid (HMB). In Experiment 1, a corn-peanut meal diet deficient in Met (0.25%
      digestible) and Cys (0.28% digestible) was fed; treatments were formulated to
      contain graded levels (0, 0.04, or 0.08%) of Met from DLM or 0.04% HMB (adjusted
      for 88% purity) that were fed in the presence or absence of surfeit isomethyl
      CHOL (0.25%) or BET (0.28%). In Experiment 2, identical treatments were used, but
      an additional level of HMB (0.08%) was fed, and the basal diet was adequate in
      Cys (0.43% digestible). There was no overall effect of CHOL or BET on growth
      performance in Experiments 1 and 2 (P > 0.05); a significant improvement (P <
      0.05) in weight gain and feed efficiency did occur with CHOL and BET addition to
      the basal diet in Experiment 2. In both experiments, weight gain increased
      linearly (P < 0.05) with the addition of DLM or HMB. Slope ratio methodology was
      used to assess HMB efficacy in Experiment 2. In the presence of adequate Cys, HMB
      efficacy was 81.3%; addition of surfeit BET or CHOL had minimal effect on
      efficacy. The stable isotope study revealed that CHOL and BET addition to diets
      deficient in Met and Cys or Met alone increased HCY remethylation. It also showed
      that CHOL and BET have greater influence on folate-dependent remethylation of HCY
      (via Met synthase) than on BET-dependent remethylation (via BET-HCY
      methyltransferase) and that levels of CHOL and BET and type of S amino acid
      deficiency effect remethylation and HMB efficacy.

PMID- 17012163
TI  - Efficacy of an Escherichia coli phytase in broilers fed adequate or reduced
      phosphorus diets and its effect on carcass characteristics.
AB  - Five experiments (EXP) were conducted to assess the efficacy of an Escherichia
      coli phytase compared with 2 commercially available fungal phytases. In EXP 1 and
      2, male broiler chicks were fed experimental diets that included a P-deficient
      control (0.13% available P; 0.88% Ca) alone or with graded levels of KH(2)PO(4)
      (0, 0.05, 0.10, or 0.15%) or phytase at levels of 250, 500, 1,000, 2,000, or
      4,000 phytase units/kg of E. coli phytase (EXP 1 and 2), fungal phytase 1 (EXP
      2), or fungal phytase 2 (EXP 2). In EXP 1 and 2, weight gain and tibia ash
      (mg/chick and %) responded linearly (P < 0.05) to inorganic P addition. In EXP 2,
      each level of E. coli phytase released more P than either fungal phytases 1 or 2,
      whether based on tibia ash weight (mg/chick) or percentage. In EXP 3, 4, and 5,
      dietary treatments containing adequate or deficient levels of P were fed with or
      without supplemental E. coli phytase. In EXP 3, weight gain and tibia ash were
      reduced (P < 0.05) by P deficiency, but gain and tibia ash of chicks fed E. coli
      phytase (250, 500, or 1,000 phytase units/kg) did not differ (P > 0.05) from that
      of chicks fed the P-adequate diet. In addition, carcass yield of broilers fed E.
      coli phytase was not reduced (P > 0.05). In EXP 4, E. coli phytase effectively
      supported weight gain, tibia ash, breast yield, and leg yield compared with birds
      fed the P-adequate diet, but clavicle breakage during processing was increased in
      birds fed E. coli phytase. In EXP 5, E. coli phytase again effectively supported
      weight gain, and no differences (P > 0.05; compared with the P-adequate diet)
      were noted for clavicle ash, diameter, or breaking strength. No differences (P >
      0.05) in bone breakage during processing were noted among treatments. These
      results indicate that the addition of E. coli phytase to P-deficient broiler
      diets improves growth, bone, and carcass performance and is more effective at
      releasing phytate-bound P than the other phytase products that were tested.

PMID- 17012164
TI  - Molecular cloning and expression of the duplicated thyroid hormone responsive
      spot 14 (THRSP) genes in ducks.
AB  - Thyroid hormone responsive Spot 14 (THRSP) is suggested as a transcription factor
      involved in the regulation of adipogenic enzymes by 3 thyroid response elements
      in the promoter region. In the chicken genome, THRSP gene was identified to
      duplicate into 2 paralogs, THRSPalpha and THRSPbeta. In the current study, cDNA
      sequences of the duplicated duck THRSP genes were cloned by real-time PCR and
      rapid amplification of cDNA ends. Duck THRSPalpha and THRSPbeta were predicted to
      encode peptides with 133 amino acids, which had 74 and 68% sequence identity at
      cDNA level, 78 and 74% identity at amino acid level to the chicken counterparts,
      respectively. A high percentage (73.1%) of G and C nucleotides were found in the
      3' untranslated region of duck THRSPbeta cDNA. Although a low similarity of
      peptide composition was shared between ducks and mammals, and a moderate
      similarity was shared between ducks and chickens, many predicted properties of
      THRSP, including the pI, subcellular localization and functional domains seemed
      to be highly conserved. The present study demonstrated that the duck THRSP gene
      duplicates into the 2 paralogs as in chickens. Phylogenetic analysis indicated
      that the duplication for THRSP paralogs appeared to have taken place preceding
      the chicken-duck split, and the diverging rate between THRSP paralogs seemed
      faster in the chicken genome than that in the duck genome. Expression analysis by
      real-time quantitative PCR showed that THRSP paralogs in ducks were more actively
      transcribed in fat tissues (i.e., s.c. fat and abdominal fat) than in liver, and
      the mRNA concentrations of THRSPbeta were higher than that of THRSPalpha in liver
      and s.c. fat.

PMID- 17012165
TI  - Turkey breeder hen age affects growth and systemic and intestinal inflammatory
      responses in female poults examined at different ages posthatch.
AB  - This trial examined the effect of 2 turkey breeder hen ages (33 or 55 wk of age)
      on performance, intestinal histology, and inflammatory immune response of female
      turkey poults grown to market weight. Using a randomized design, female poults
      were separated by breeder flock age (n = 8 floor pens/breeder flock age; n = 26
      poults/pen; 0.195 m(2)/bird), fed identical commercial diets (9 phases), and
      grown to market weight (approximately 11.4 kg/ bird). At young ages, poults from
      the older breeder flock tended to have higher BW (P < 0.01 for d 7, P < 0.09 for
      d 63), although feed consumed was not significantly different due to breeder
      flock age (P > 0.20 for all ages). After approximately 63 d posthatch, no
      difference in BW was observed, suggesting that poults from the younger breeder
      flock were eventually able to compensate for initial reductions in performance.
      In addition to growth measurements on d 10, 24, and 65 posthatch, poults were
      vaccinated with lipopolysaccharide (LPS, from Salmonella Typhimurium; 0.5 mg/kg
      of BW intraabdominally) or not vaccinated (control), and intestinal histology and
      plasma haptoglobin were assessed at 24 h postadministration. In control birds,
      intestinal villus length was greater for poults from the older breeder flock (P <
      0.05), as was crypt depth (P < 0.05 for d 11 and 25). Plasma haptoglobin levels
      did not change in 11-d-old poults after LPS administration, but they increased
      with LPS at d 25 and 66 posthatch (P < 0.05 for each). At d 66 posthatch, poults
      from the younger flock had increased haptoglobin levels post-LPS compared with
      those from the older breeder flock (P < 0.05). In general, LPS administration
      increased villus width in the jejunum and ileum (P < 0.05 for each), increased
      lamina propria width in the duodenum and ileum (P < 0.05 for each), and decreased
      ileum crypt depth (P < 0.05). Overall, poults from the older breeder flock had
      reduced inflammatory responses, even at 9 to 10 wk posthatch, even though
      performance was similar in poults from the 2 flocks by this age.

PMID- 17012166
TI  - Production of chick germline chimeras from fluorescence-activated cell-sorted
      gonocytes.
AB  - Modification of the chicken germline has been difficult, because it has been
      challenging to fractionate sufficient numbers of primordial germ cells for
      manipulation and implantation into developing embryos. A technique to enrich cell
      suspensions for primordial germ cells, using fluorescence-activated cell sorting
      (FACS), has recently been developed. The objective of the current study was to
      demonstrate that the FACS-enriched early embryonic gonocytes could fully
      participate in development of the germline. Therefore, cells were disassociated
      from stage 27 gonads, incubated with mouse anti-stage-specific embryonic antigen
      1, which was detected with goat-antimouse IgM-fluorescein isothiocyanate, and the
      fluorescently labeled cells were sorted from the unlabeled cells using FACS. The
      isolated gonocyte population was injected into the blastoderm of unincubated
      stage X embryos, the germinal crescent of 3-d embryos, and into the circulation
      of stage 17 embryos that were pretreated with busulfan. Barred Plymouth Rock
      gonocytes were implanted exclusively into recipient White Leghorn embryos, and
      White Leghorn gonocytes were implanted exclusively into Barred Plymouth Rock
      recipient embryos. Embryos were cultured until hatch, and male putative chimeras
      were reared to sexual maturity. Germline chimerism was evaluated by observing
      feather color of the progeny. All injection methods resulted in germline chimeras
      demonstrating that FACS-sorted gonocytes can fully participate in development.
      Moreover, it was demonstrated that gonocytes isolated from stage 27 embryonic
      gonads can be introduced into embryos at an earlier stage of development, and the
      introduced gonocytes can fully participate in germline development.

PMID- 17012167
TI  - Activity of three-beta-hydroxysteroid dehydrogenase in granulosa cells treated in
      vitro with luteinizing hormone, follicle-stimulating hormone, prolactin, or a
      combination.
AB  - Three-beta-hydroxysteroid dehydrogenase (3beta-HSD) is a key enzyme in the
      pathway that produces progesterone. Hy-Line hens (W36, W98, and Brown) were
      subjected to mild heat stress [36 degrees C for 24 h (acute heat stress, AHS) or
      2 wk (chronic heat stress, CHS)] or maintained at 22 degrees C (thermoneutral,
      TN). Granulosa cells (GC) from the 3 largest follicles were isolated, dispersed,
      and incubated with luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      prolactin (PRL), a combination, or no hormone (control), and then with
      pregnenolone nitro blue tetrazolium to determine 3beta-HSD activity. Treatment by
      LH (TN, P = 0.04; AHS, CHS, P < 0.0001) and by LH+FSH (TN, AHS, CHS, P < 0.0001)
      resulted in increased enzyme activity compared with the respective controls. In
      TN and CHS, LH+FSH increased the activity to a greater extent than LH alone (TN,
      P = 0.02; CHS, P = 0.0004); in AHS the increase was not significant (P = 0.29).
      Treatment with FSH, PRL, or LH+PRL decreased (TN, AHS) or had no effect (CHS) on
      3beta-HSD activity. In TN and AHS cells, FSH and PRL reduced enzyme activity (P =
      0.006 and 0.0580, respectively). When LH was added to PRL, suppression by PRL was
      mitigated somewhat. When LH and FSH were added to PRL, 3beta-HSD activity in AHS
      and CHS cells actually increased compared with the respective controls (P = 0.052
      and 0.003) but remained below the activity of cells incubated with LH+FSH or LH
      alone. This suggests that gonadotropic actions of LH and LH+FSH are countered by
      the antigonadotropic action of PRL and, conversely, that PRL reduces the
      stimulatory action of LH and FSH. Strain differences in GC response to hormones
      were observed primarily in the CHS-treated birds; generally, W98 was highest;
      Browns showed the weakest response, and W36 was intermediate. In earlier studies,
      HS reduced circulating LH and GC progesterone and 3beta-HSD activity in vitro and
      increased circulating PRL. The results suggest a mechanism by which reduced
      activity of 3beta-HSD and progesterone by GC during HS might be explained,
      particularly with the differences in strains observed.

PMID- 17012168
TI  - Energy partitioning and thyroid hormone levels during Salmonella enteritidis
      infections in pullets with high or low residual feed intake.
AB  - This experiment was conducted to investigate whether feed efficiency, as measured
      by residual feed intake as a phenotypic trait, affects energy partitioning in
      pullets that have received Salmonella inoculation as an immune challenge. In each
      of 8 trials, energy partitioning was measured during 5 wk in 15-wk-old efficient
      (R-) and nonefficient (R+) pullets, which were housed per efficiency group in 2
      identical climate respiration chambers. After 1 wk of adaptation, the pullets in
      4 trials were orally inoculated with 10(8) cfu of Salmonella enteritidis; pullets
      in the remaining trials were not inoculated and served as controls. Heat
      production was calculated from continuous recordings of O(2) consumption and
      CO(2) production. Energy and N partitioning were recorded on a weekly basis.
      Blood samples for analyses on thyroid hormones were taken at 16, 17, and 19 wk of
      age. There were no interactions between efficiency type and Salmonella treatment
      or Salmonella treatment effects in energy partitioning, except for a short-term
      increase in heat production in inoculated pullets. Nonefficient pullets had
      higher gross energy and ME intake, higher estimated ME for maintenance, lower
      ME:gross energy ratio, and higher total heat production and nonactivity-related
      heat production compared with R- pullets. Triiodothyronine levels in R+ pullets
      were higher at 16 and 17 wk but were lower at 19 wk of age compared with R-
      pullets. Thyroxine levels were higher in R- at 16 wk and showed interactions
      between efficiency type and Salmonella treatment at 17 and 19 wk of age. Body
      weights and spleen weights did not differ between efficiency groups. Nonefficient
      pullets had higher heart, liver, and ovary weights and more large yellow
      follicles than R- pullets. There were no Salmonella effects on body and organ
      weights. We conclude that R+ pullets have a faster running energy metabolism and
      that they put more resources into organ development than R- pullets. Inoculation
      with Salmonella has a short-term effect on nonactivity-related heat production
      but does not affect energy partitioning, regardless of efficiency type.

PMID- 17012169
TI  - A method for cryopreserving chicken primordial germ cells.
AB  - This study established a method for preserving chicken primordial germ cells
      (PGC) that enables long-term storage in liquid N. Gonads were harvested from
      stage 27 chick embryos and pooled in groups of 5, 10 (10E), or 20 embryos,
      contributing gonads to the cell suspension. The gonadal cells, including PGC,
      were then frozen in 1 of the following cryoprotectant treatments: 2.5% dimethyl
      sulfoxide (DMSO), 5% DMSO, 10% DMSO, 2.5% ethylene glycol (EG), 5% EG, 10% EG,
      and 0% cryoprotectant as a control. The cells were liberated and frozen in a
      biosecure cryopreservation straw at a rate of -1 degrees C/min until reaching -85
      degrees C and were then plunged into liquid N (-196 degrees C), in which they
      were stored until analysis. Flow cytometry was used to analyze the PGC post-thaw.
      The PGC marker stage-specific embryonic antigen-1, which was detected with goat
      antimouse IgM fluorescein isothiocyanate, was used to label all PGC, and
      propidium iodide was used to detect cells with compromised cell membranes. There
      was an interaction effect for the number of viable PGC per individual embryo (P <
      or = 0.05). The highest level (183.6 +/- 28.4) of viable PGC per individual
      embryo was observed for 10% EG with 10E and was significantly higher (P < or =
      0.05) than cryopreservation in 2.5% DMSO with 10E and 20 embryos, 2.5% EG with
      10E, 5% EG with 10E, and all 0% cryoprotectant treatments. No statistical
      interaction (P > 0.05) was observed for the percentage of viable PGC. However,
      the highest percentage (80.6%) was observed at 10% EG with 10E. It was
      demonstrated that PGC were successfully frozen, and the most effective treatment
      was 10% EG with 10 embryos/straw.

PMID- 17012170
TI  - Comparison of plasma uric acid levels in five varieties of the domestic turkey,
      Meleagris gallopavo.
AB  - Plasma uric acid (PUA) is a consensus physiological biomarker for many phenotypes
      in vertebrates because it is a reliable indicator for processes such as oxidative
      stress and tubular function. In birds, it is considered a major antioxidant and
      is also the primary endproduct of nitrogen metabolism. Despite this importance,
      knowledge of baseline levels of PUA in physiologically normal birds, including
      the turkey, Meleagris gallopavo, is limited. Here, we compared PUA levels in a
      total of 106 apparently normal male and female birds at 8 and 32 wk of age from 5
      strains of the domestic turkey, including Bourbon Red, Narragansett, Blue Slate,
      Royal Palm, and Spanish Black. Though differences in PUA were not significant at
      8 and 32 wk of age, BW, variety, and sex effects were highly significant. When
      adjusted for BW, female birds had, on average, a higher PUA per kilogram of BW
      than male birds. When adjusted for both sex and BW, Royal Palm birds had the
      lowest average PUA, and Blue Slate had the highest PUA. Results of these
      investigations represent the first comparative analysis of PUA in physiologically
      normal turkey varieties. They suggest that differences in basal plasma levels of
      uric acid in physiologically normal turkeys are influenced by sex, weight, and
      genetic background but may be independent of age.

PMID- 17012172
TI  - Effects of packaging systems on the natural microflora and acceptability of
      chicken breast meat.
AB  - The effect of 3 packaging systems on the spoilage microflora, objective color,
      and sensory characteristics of fresh commercial broiler chicken breast meat was
      investigated. Fresh skinless and boneless chicken broiler breasts were purchased
      from a local poultry processing plant and packaged in either (1) a conventional
      Styrofoam tray with polyvinyl chloride overwrap and absorbent pad, (2) a
      Styrofoam tray with polyvinyl chloride overwrap minus absorbent pad, or (3) a
      Fresh-R-Pax (FRP) container equipped with an absorbent liner-gel system. All
      packages were heat sealed and stored at 1.2 +/- 1 degrees C for 8 d. At each
      sampling period (0, 2, 4, 6, and 8 d), packages from each treatment were analyzed
      for Pseudomonas spp., psychrotrophic organisms, objective color, and sensory
      characteristics. In general, Pseudomonas spp. and psychrotrophic counts increased
      as storage time increased for all packaging systems. Color and overall appearance
      were similar (P >0.05) for all packaging systems. Although not significant, the
      off-odor scores for breast meat packaged in FRP were higher (P >0.05) after 6 and
      8 d when compared with the breast meat packaged in a Styrofoam tray with
      polyvinyl chloride overwrap with or without an absorbent pad. Although the
      absorbent pad did not control microbial growth, it maintained aesthetic appeal by
      absorbing all visible moisture released from the meat during storage.

PMID- 17012171
TI  - Evaluation of corn furan fatty acid putative endocrine disruptors on reproductive
      performance in adult female chickens.
AB  - Based on evidence from rodent models, it was hypothesized that furan fatty acids
      found in corn would inhibit reproduction in the laying hen. An isomeric mixture
      of furan fatty acids [9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy
      9,12-dihydroxystearic acid] was administered for a period of 3 wk via the diet (1
      and 3 ppm) at levels greater than those in corn to 20-wk-old pullets. There were
      no overt indications of acute or chronic toxicity (no effects on mortality, feed
      intake, or average daily gain). Similarly, there was no dose-dependent effect on
      reproductive parameters [egg production, egg weight, shell thickness, ovarian
      weight, number or weight of large yolky preovulatory follicles, and number of
      small yellow follicles (4-8 mm in diameter)]. The present data do not suggest
      that furan fatty acids are a cause of concern to the poultry industry.

PMID- 17012173
TI  - Broiler carcass bacterial counts after immersion chilling using either a low or
      high volume of water.
AB  - A study was conducted to investigate the bacteriological impact of using
      different volumes of water during immersion chilling of broiler carcasses. Market
      aged broilers were processed, and carcasses were cut into left and right halves
      along the keel bone immediately after the final bird wash. One half of each
      carcass pair was individually chilled at 4 degrees C in a separate bag containing
      either 2.1 L/kg (low) or 16.8 L/kg (high) of distilled water. Carcass halves were
      submersed in a secondary chill tank containing approximately 150 L of an ice
      water mix (0.6 degrees C). After chilling for 45 min, carcass halves were rinsed
      with 100 mL of sterile water for 1 min. Rinses and chill water were analyzed for
      total aerobic bacteria (APC), Escherichia coli, Enterobacteriaceae, and
      Campylobacter. After chilling with a low volume of water, counts were 3.7, 2.5,
      2.6, and 2.1 log(10) cfu/mL of rinse for APC, E. coli, Enterobacteriaceae, and
      Campylobacter, respectively. When a high volume of chill water was used, counts
      were 3.2, 1.7, 1.6, and 1.8 log(10) cfu/mL of rinse for APC, E. coli,
      Enterobacteriaceae, and Campylobacter, respectively. There was no difference in
      bacterial counts per milliliter of chill water among treatments. These results
      show that using additional water during immersion chilling of inoculated broilers
      will remove more bacteria from the carcass surfaces, but numbers of bacteria per
      milliliter in the chiller water will remain constant. The bacteriological impact
      of using more water during commercial immersion chilling may not be enough to
      offset economic costs.

PMID- 17012174
TI  - Release of Escherichia coli from feathered and featherless broiler carcasses in
      warm water.
AB  - Release of bacteria from individual broiler carcasses in warm water was measured
      as a model of bacterial contamination of scald water. Immediately after shackling
      and electrocution, feathered and genetically featherless broiler carcasses (n =
      24 of each) were immersed individually in 42 degrees C, air-agitated tap water
      for 150 s. Although any visible fecal material expelled as a result of
      electrocution was removed before sampling, carcass condition was typical for
      market-age broilers subjected to 12 h of feed withdrawal. Duplicate water samples
      were taken at 10, 30, 70, 110, and 150 s, and Escherichia coli counts were
      determined. Samples of initial tap water and contaminated water approximately 2
      min after removal of carcasses indicated that E. coli could not be detected in
      the original water source and that mortality of E. coli in the warm water was
      negligible. Mean numbers of E. coli released were 6.2 and 5.5 log(10)
      (cfu/carcass) at 150 s for feathered and featherless carcasses, respectively. For
      both feathered and featherless carcasses, the rate of release of E. coli was
      highest in the first 10 s, and the rate declined steadily during the remaining
      sampling period. This result is compatible with published reports of sampling of
      operating multiple-tank scalders, indicating that a high proportion of total
      bacteria in a multiple-tank scalder are in the first scald tank that carcasses
      enter. Higher numbers of E. coli released from feathered carcasses are probably
      due to the much greater surface area of contaminated feathers compared with the
      skin of featherless carcasses.

PMID- 17012175
TI  - Effect of dry honey on the shelf life of packaged turkey slices.
AB  - The development of off-flavors from oxidation reactions in cooked turkey products
      is a common problem and results in a less desirable, rancid flavor. Various
      strategies have been evaluated to minimize this off-flavor development, including
      vacuum and modified atmosphere packaging, feeding antioxidants to animals, and
      use of antioxidants in the final product. A natural protein-sugar reaction called
      the Maillard reaction produces a brown pigment, flavors, and antioxidants. This
      research tested the addition of honey to turkey breast meat before processing to
      retard production of oxidation products related to off-flavor. Three levels (0,
      5, 15%) of dry honey were mixed with raw turkey breast meat pieces, then the
      mixture was stuffed into casing and cooked. The cooking process facilitated the
      Maillard reaction and the development of an antioxidative effect. The cooked
      chubs were then cooled, sliced, and vacuum-packaged as individual slices. The
      slices were refrigerated and tested for color, flavor, oxidative rancidity, and
      microbial growth over 11 wk. Sensory panelists detected increased sweetness and
      no negative flavor impact on acceptability for turkey with added honey. The
      addition of honey enhanced the oxidative stability of the meat, as indicated by
      lower TBA values, hexanal content, and oxidative stability index. Honey did
      impart a slightly darker color with lower lightness values but had no effect of
      redness and yellowness values.

PMID- 17012176
TI  - Growth depth effects of bacteria in ground turkey meat patties subjected to high
      carbon dioxide or high oxygen atmospheres.
AB  - Modified atmosphere packaging (MAP) is used to extend the shelf life of ground
      meats by altering the gas atmosphere surrounding the meat. This study evaluated
      how deep MAP bactericidal effects penetrate into a ground meat patty. Patties
      made from freshly ground turkey breasts were subjected to 2 MAP treatments of
      high CO(2) (97%) or high O(2) (80% O(2), 20% CO(2)). Total plate and lactic acid
      bacterial counts were determined for 3 patty depths (top, middle, bottom). Meat
      surface color and the package gas headspace composition were also measured. All
      analyses were performed on 0, 3, 6, 9, and 12 d. Changes in gas headspace and
      meat surface color were also measured at 0, 3, 6, 9, and 12 d. High CO(2)
      atmosphere maintained a better meat surface color than high O(2) atmosphere over
      the whole storage period. Overall counts were lower (P < or = 0.05) in a high
      CO(2) atmosphere compared with a high-O(2) modified atmosphere. Patties stored
      under a high-CO(2) atmosphere displayed slower bacterial growth in the top layer
      compared with the middle and bottom layers. Total plate count did not differ (P >
      or = 0.05) in layers for patties pack-aged in a high-O(2) atmosphere Lactic acid
      bacterial counts increased in the high-O(2) modified atmosphere by d 9 and 12 of
      storage; no increase was observed in CO(2)-packaged patties. Thus, high-CO(2) MAP
      slowed the growth of total bacteria as well as lactic acid bacteria. Also, there
      was slower growth in the top meat layer exposed to CO(2) compared with interior
      layers.

PMID- 17012178
TI  - Salmonella prevalence in market-age turkeys on-farm and at slaughter.
AB  - The objective of this study was to compare the prevalence of Salmonella in market
      age turkeys on-farm and at slaughter (i.e., before and after feed withdrawal,
      catching, loading, transportation, and preslaughter holding). Thirty birds were
      randomly selected from each of 6 commercial turkey flocks scheduled to be loaded
      and shipped to the abattoir during the evening of the same day. Selected birds
      were euthanized on the farm, and the cloacal contents, large intestine, crop,
      ceca, liver and gallbladder, and spleen were aseptically collected. At the
      abattoir, 30 birds from the same flock were randomly selected from the slaughter
      line, and the crop, ceca, liver and gallbladder, and spleen were collected for
      subsequent culture at the laboratory. All flocks studied were positive for
      Salmonella at slaughter. No statistical difference was found between the overall
      prevalence on-farm and at slaughter. At both sampling points, the overall
      prevalence found was 33.3%. Diverging prevalence estimates were obtained based on
      the different sample types collected on-farm and at slaughter. In both cases,
      cecal content samples had the highest relative sensitivity (73.3% on-farm and
      68.3% at slaughter). This study demonstrates that the preslaughter practices of
      feed withdrawal, catching, loading, transportation, and holding do not
      significantly alter the prevalence of Salmonella in market-age turkeys.
      Therefore, our results suggest that it may be possible to monitor the Salmonella
      status of turkey production farms based on samples collected at the abattoir.

PMID- 17012177
TI  - Dietary functional ingredients: performance of animals and quality and storage
      stability of irradiated raw turkey breast.
AB  - The objective of this study was to evaluate the effect of dietary functional
      ingredients vitamin E (VE), Se, and conjugated linoleic acid (CLA), alone or in
      combination, on the quality of irradiated turkey breast meat. A total of 480 male
      turkeys (11-wk-old, raised on a cornsoybean basal diet) were randomly allotted to
      32 pens and fed 1 of 8 experimental diets (4 pens/treatment) supplemented with
      none (control), 200 IU/kg of VE (VE), 0.3 ppm Se (Se), 2.5% CLA (CLA), 200 IU/kg
      of VE + 0.3 ppm Se (VE + Se), 200 IU/kg of VE + 2.5% CLA (VE + CLA), 2.5% CLA +
      0.3 ppm Se (CLA + Se), 200 IU/kg of VE + 0.3 ppm Se + 2.5% CLA (VE + Se + CLA)
      for 4 wk. At 15 wk of age, all birds were slaughtered, and breast muscles of 8
      birds from each pen were separated, pooled, and ground. Patties were prepared
      using the ground meat, aerobically packaged, and irradiated at 0 or 1.5 kGy
      absorbed dose. Lipid oxidation, color, and volatiles of the patties were measured
      after 0, 7, and 12 d of storage at 4 degrees C. The content of VE and Se and
      fatty acid composition of lipids were also determined. Dietary supplementation of
      VE and CLA increased their concentrations in turkey breast. Dietary CLA decreased
      monounsaturated and non-CLA polyunsaturated fatty acids content in meat.
      Irradiation increased (P < 0.05) Hunter color redness value of turkey breast and
      accelerated lipid oxidation, regardless of dietary treatments. However, dietary
      VE, Se, and CLA, alone and in combinations, decreased (P < 0.05) lipid oxidation
      in meat caused by both irradiation and storage. It was concluded that dietary
      supplementation of VE, Se, and CLA, alone and in combination, improved the
      storage stability of irradiated turkey breast meat.

PMID- 17012179
TI  - The occurrence of deep pectoral myopathy in roaster chickens.
AB  - A study was conducted to determine the incidence of deep pectoral myopathy (DPM)
      in male roaster chickens reared under intensive conditions, processed at
      different ages (from 47 to 65 d of age), and belonging to 2 commercial genotypes
      (Ross 508 and Cobb 500). The study was carried out in a major Italian processing
      plant on a total of 120,700 male roaster chickens chosen at random from 151
      flocks during a 6-mo period. The evaluation of DPM was performed on pectoralis
      minor muscles and consisted of a visual assessment of the presence or absence of
      the myopathy as well as the scoring of muscle damage level as being in an "early"
      (hemorrhagic appearance) or "old" (gray or green discoloration) developing stage.
      The average incidence of carcasses affected by DPM was found to be 0.84% (0.62
      and 0.22% in early and old stages, respectively). The range in the incidence of
      total DPM was fairly large and varied from 0 to 16.7%. Considerable variations
      were also observed for early (range: 0 to 12.0%) and old (range: 0 to 5.6%)
      developing stages. Considering the effect of genotype, Ross 508 exhibited a
      higher incidence of DPM in respect to Cobb 500 (1.27 vs. 0.35%; P < or = 0.01).
      This result was due to the higher incidence of carcasses affected by both early
      (0.94 vs. 0.26%; P < or = 0.01) and old (0.33 vs. 0.09%; P < or = 0.01)
      developing stages of DPM in Ross 508 birds.

PMID- 17012180
TI  - Effect of varying metabolizable energy and crude protein concentrations in diets
      of Pearl Gray guinea fowl pullets 1. Growth performance.
AB  - This study was undertaken to assess dietary ME and CP concentrations for optimum
      growth performance of Pearl Gray guinea fowl pullets. In a 3 x 3 factorial
      arrangement, 540 one-day-old Pearl Gray guinea keets were randomly assigned to
      experimental diets with 2,900, 3,000, and 3,100 kcal of ME/kg of diet, each
      containing 20, 22, and 24% CP, respectively, from 0 to 8 wk of age (WOA). From 9
      to 16 WOA, these diets were adjusted to contain 3,000, 3,100, and 3,200 kcal of
      ME/ kg, and each had 17, 19, and 21% CP, respectively. Each dietary treatment was
      replicated 4 times, and feed and water were provided ad libitum. Body weight and
      feed consumption were measured weekly. Mortality was recorded as it occurred.
      Overall, feed consumption was higher in birds on 2,900 and 3,000 kcal of ME/kg of
      feed and the 24 and 21% CP diets than other dietary treatments at 0 to 8 and 9 to
      16 WOA, respectively. When compared with other dietary treatments, cumulative BW
      gains were higher (P < 0.05) in birds fed 3,000, 3,000 and 3,100, and 3,100 and
      3,200 kcal of ME/kg of diet at 2 to 5, 6 to 8, and 9 to 16 WOA, respectively.
      Pullets receiving 24 and 21% CP diets also exhibited higher BW gains than other
      dietary treatments at 0 to 8 and 9 to 16 WOA, respectively. Feed conversion
      ratios were lower (P < 0.05) in birds fed 3,000, 3,100, and both 3,100 and 3,200
      kcal of ME/kg of diet at 1 to 5, 6 to 8, and 9 to 16 WOA, respectively, than
      other dietary treatments. Pullets fed 24% CP diets and either 17 or 19% CP diets
      exhibited lower (P < 0.05) feed conversion ratios than other dietary treatments
      at 1 to 8 and 9 to 16 WOA, respectively. Thus, diets comprising 3,000 and 3,100
      kcal of ME/kg were utilized more efficiently by the Pearl Gray guinea fowl
      pullets at 0 to 5 and 5 to 16 WOA, respectively. Also, these birds more
      efficiently utilized diets containing 24 and 17% CP at 0 to 8 and 9 to 16 WOA,
      respectively.

PMID- 17012181
TI  - Investigating the effects of commercial probiotics on broiler chick quality and
      production efficiency.
AB  - A study was undertaken to test the effect of 2 commercially available probiotics
      on the production efficiency of broiler chickens hatched from the same breeder
      flock at 3 different ages (28, 43, and 57 wk). At each of the 3 breeder flock
      ages, 1,600 broiler chickens were hatched and randomly allocated to 1 of 4
      treatments: 1) no probiotics (control), 2) probiotic 1 administered in the
      drinking water, 3) probiotic 1 administered as a spray, and 4) probiotic 2
      administered in the feed. A coccidiostat was included in the feed, but no other
      antimicrobial agents were given. Broilers were then reared on straw litter in
      identical floor pens for a period of 6 wk. There were no significant differences
      in broiler BW, feed conversion, or mortality between the probiotic treatments and
      the control group in any of the trials. The 43-wk-old breeder flock had the
      highest fertility and hatchability and the lowest percentage of chicks culled at
      hatching. Throughout the broiler production period, the broilers from the 43- and
      57-wk-old breeder flocks had higher BW and weight gains than the broilers
      produced at 28 wk of breeder flock age. Broiler feed conversion over the 6-wk
      production period decreased as the breeder flock aged. Probiotics had no effect
      on chick quality or production efficiency in broilers produced by the breeder
      flock ages examined.

PMID- 17012182
TI  - Approaches to biology teaching and learning: on integrating pedagogical training
      into the graduate experiences of future science faculty.

PMID- 17012183
TI  - WWW: the scientific method.

PMID- 17012184
TI  - Education at the national academies: three recent reports on improving science
      education.

PMID- 17012185
TI  - Meeting report: teaching signal transduction.
AB  - In July, 2005, the European Institute of Chemistry and Biology at the campus of
      the University of Bordeaux, France, hosted a focused week of seminars, workshops,
      and discussions around the theme of "teaching signal transduction." The purpose
      of the summer school was to offer both junior and senior university instructors a
      chance to reflect on the development and delivery of their teaching activities in
      this area. This was achieved by combining open seminars with restricted access
      workshops and discussion events. The results suggest ways in which systems
      biology, information and communication technology, Web-based investigations, and
      high standard illustrations might be more effectively and efficiently
      incorporated into modern cell biology courses.

PMID- 17012186
TI  - FIRST--what's next?

PMID- 17012187
TI  - High school biology today: what the committee of ten did not anticipate.

PMID- 17012188
TI  - Criticism and interpretation: teaching the persuasive aspects of research
      articles.
AB  - Research articles are an excellent tool for promoting active learning about the
      scientific process. One difficulty in teaching research articles is that they
      address a professional audience and often seek to be persuasive as well as
      informative. This essay discusses pedagogical strategies that are intended to
      help students differentiate the purely informative aspects of research articles,
      such as descriptions of the methods and results, from the persuasive aspects,
      such as interpretation of results and critical evaluation of the work of other
      scientists.

PMID- 17012190
TI  - A small-scale concept-based laboratory component: the best of both worlds.
AB  - In this article, we describe an exploratory study of a small-scale, concept
      driven, voluntary laboratory component of Introductory Biology at the
      Massachusetts Institute of Technology. We wished to investigate whether students'
      attitudes toward biology and their understanding of basic biological principles
      would improve through concept-based learning in a laboratory environment. With
      these goals in mind, and using our Biology Concept Framework as a guide, we
      designed laboratory exercises to connect topics from the lecture portion of the
      course and highlight key concepts. We also strove to make abstract concepts
      tangible, encourage learning in nonlecture format, expose the students to
      scientific method in action, and convey the excitement of performing experiments.
      Our initial small-scale assessments indicate participation in the laboratory
      component, which featured both hands-on and minds-on components, improved student
      learning and retention of basic biological concepts. Further investigation will
      focus on improving the balance between the minds-on concept-based learning and
      the hands-on experimental component of the laboratory.

PMID- 17012191
TI  - Incorporating a new bioinformatics component into genetics at a historically
      black college: outcomes and lessons.
AB  - Many students at minority-serving institutions are underexposed to Internet
      resources such as the human genome project, PubMed, NCBI databases, and other Web
      based technologies because of a lack of financial resources. To change this, we
      designed and implemented a new bioinformatics component to supplement the
      undergraduate Genetics course at Clark Atlanta University. The outcomes of the
      Bioinformatics course were assessed. During the first week of the semester,
      students were assigned the Felder-Soloman's Index of Learning Styles Inventory.
      The overwhelming majority of students were visual (82.1%) and sequential (75.0%)
      learners. Furthermore, pre- and postcourse surveys were administered during the
      first and the last week of the course to assess learning, confidence level, and
      mental activity. These indicated students increased the number of hours spent
      using computers and doing homework. Students reported confidence in using
      computers to study genetics increased, enabling them to better visualize and
      understand genetics. Furthermore, students were more mentally engaged in a more
      social learning environment. Although the students appreciated the value of the
      bioinformatics component, they reported the additional work load was substantial
      enough to receive additional course credit.

PMID- 17012192
TI  - Student perspectives on curricular change: lessons from an undergraduate lower
      division biology core.
AB  - Inquiry-based laboratories are acknowledged as the preferred method of
      instruction for development of research skills. Much has been written about
      changes in student performance associated with inquiry, but less is known about
      how students view the inquiry-based format or whether they perceive a benefit
      from this type of instruction. The Student Assessment of Learning Gains (SALG)
      survey was used to evaluate and compare student reactions to the new, inquiry
      based laboratories of a lower-division undergraduate curriculum, from
      implementation to the present (an interval of 3 yr). Initial student response to
      the format and value of the inquiry labs improved over time. The quality of the
      graduate teaching assistants and the clarity of the laboratory manual were
      important variables influencing student perception. A student's perception of
      his/her retention of lab-related skills was strongly associated with perceptions
      of gains in those skills. Student responses reflect their most current laboratory
      experience and not a cumulative effect of participation in the core series of
      courses. Student success in the inquiry format was not associated with gender or
      status as a transfer student. The majority of students believe that their
      experiences in the lower-division inquiry labs have prepared them for upper
      division course work.

PMID- 17012193
TI  - General chemistry: expanding the learning outcomes and promoting
      interdisciplinary connections through the use of a semester-long project.
AB  - The laboratory component of a first-semester general chemistry course for science
      majors is described. The laboratory involves a semester-long project undertaken
      in a small-group format. Students are asked to examine whether plants grown in
      soil contaminated with lead take up more lead than those grown in uncontaminated
      soil. They are also asked to examine whether the acidity of the rainwater affects
      the amount of lead taken up by the plants. Groups are then given considerable
      independence in the design and implementation of the experiment. Once the seeds
      are planted, which takes about 4 wk into the term, several shorter experiments
      are integrated in before it is time to harvest and analyze the plants. The use of
      a project and small working groups allows for the development of a broader range
      of learning outcomes than occurs in a "traditional" general chemistry laboratory.
      The nature of these outcomes and some of the student responses to the laboratory
      experience are described. This particular project also works well at
      demonstrating the connections among chemistry, biology, geology, and
      environmental studies.

PMID- 17012194
TI  - From faculty for undergraduate neuroscience: encouraging innovation in
      undergraduate neuroscience education by supporting student research and faculty
      development.

PMID- 17012195
TI  - Strategy for engaging the Society for Neuroscience in science education.

PMID- 17012196
TI  - WWW: neuroscience web sites.

PMID- 17012197
TI  - Video views and reviews: neurulation and the fashioning of the vertebrate central
      nervous system.

PMID- 17012198
TI  - Points of view: on the implications of neuroscience research for science teaching
      and learning: are there any? A skeptical theme and variations: the primacy of
      psychology in the science of learning.

PMID- 17012199
TI  - Points of view: on the implications of neuroscience research for science teaching
      and learning: are there any?

PMID- 17012203
TI  - Neuroscience workshops for fifth-grade school children by undergraduate students:
      a university-school partnership.
AB  - The National Science Education Standards recommend that science be taught using
      inquiry-based approaches. Inspired by the Dana Alliance for Brain Initiatives, we
      examined whether undergraduate students could learn how to conduct field research
      by teaching elementary school children basic neuroscience concepts in interactive
      workshops. In an inquiry-based learning experience of their own, undergraduate
      psychology students working under the close supervision of their instructor
      designed and provided free, interactive, hour-long workshops focusing on brain
      structure and function, brain damage and disorders, perception and illusions, and
      drugs and hormones to fifth-graders from diverse backgrounds, and we assessed the
      effectiveness of the workshops using a pretest-post-test design. The results
      suggest that the workshops enhanced the children's knowledge of neuroscience
      concepts as measured using pre- and post-open-ended assessments. The
      undergraduates also found their learning experience engaging and productive. The
      article includes detailed descriptions of the workshop activities, procedures,
      the course in which the undergraduates implemented the workshops, and guidance
      for future university-school collaborations aimed at enhancing science literacy.

PMID- 17012204
TI  - An online, interactive approach to teaching neuroscience to adolescents.
AB  - Most of today's students are skilled in instant messaging, Web browsing, online
      games, and blogs. These have become part of the social landscape and have changed
      how we learn and where we learn. The question becomes how to harness the
      attractiveness and ubiquity of electronic venues toward the goal of teaching
      neuroscience. At the Rice University Center for Technology in Teaching and
      Learning, a central focus is the creation of innovative materials that appeal to
      middle school students. A recent project was undertaken through a Science
      Education Drug Abuse Partnership Award (R25 DA15063) from the National Institute
      on Drug Abuse to inform adolescents about the neurobiology of substance abuse and
      the current research dealing with a class of drugs known as club drugs. Problem
      based learning, multimedia pedagogy, and the National Science Content Standards
      were integrated to produce The Reconstructors, an episodic series available via
      the World Wide Web at http://reconstructors.rice.edu. A field test of students
      from five schools assessed the retention of content after "playing" The
      Reconstructors series titled Nothing to Rave About. Gain scores indicated that
      middle school students' knowledge about club drugs and the basic neuroscience
      concepts that explain their effects improved significantly.

PMID- 17012205
TI  - Neuroscience in middle schools: a professional development and resource program
      that models inquiry-based strategies and engages teachers in classroom
      implementation.
AB  - The Department of Neuroscience at the University of Minnesota and the Science
      Museum of Minnesota have developed and implemented a successful program for
      middle school (grades 5-8) science teachers and their students, called Brain
      Science on the Move. The overall goals have been to bring neuroscience education
      to underserved schools, excite students about science, improve their
      understanding of neuroscience, and foster partnerships between scientists and
      educators. The program includes BrainU, a teacher professional development
      institute; Explain Your Brain Assembly and Exhibit Stations, multimedia large
      group presentation and hands-on activities designed to stimulate student thinking
      about the brain; Class Activities, in-depth inquiry-based investigations; and
      Brain Trunks, materials and resources related to class activities. Formal
      evaluation of the program indicated that teacher neuroscience knowledge, self
      confidence, and use of inquiry-based strategies and neuroscience in their
      classrooms have increased. Participating teachers increased the time spent
      teaching neuroscience and devoted more time to "inquiry-based" teaching versus
      "lecture-based teaching." Teachers appreciated in-depth discussions of pedagogy
      and science and opportunities for collegial interactions with world-class
      researchers. Student interest in the brain and in science increased. Since
      attending BrainU, participating teachers have reported increased enthusiasm about
      teaching and have become local neuroscience experts within their school
      communities.

PMID- 17012206
TI  - Brains Rule!: a model program for developing professional stewardship among
      neuroscientists.
AB  - Brains Rule! Neuroscience Expositions, funded through a National Institute on
      Drug Abuse Science Education Drug Abuse Partnership Award, has developed a
      successful model for informal neuroscience education. Each Exposition is a
      "reverse science fair" in which neuroscientists present short neuroscience
      teaching modules to students. This study focuses on results of assessments
      conducted with neuroscientist presenters during Expositions at two sites,
      Atlanta, Georgia and Corpus Christi, Texas. The effects of participating in the
      Expositions on presenters' perceptions of their own presentation and
      communication skills were evaluated, as was the potential for increased active
      participation by neuroscientists in future outreach programs. In four of the five
      Expositions studied, pre- versus post-event surveys demonstrated significant
      changes in presenters' perceptions of their own abilities to explain neuroscience
      concepts to children. Over the course of an Exposition, presenters learned to fit
      their approaches to conveying neuroscience concepts to fifth through eighth
      graders and learned to link information they presented about the brain and
      nervous system to children's past experiences to improve comprehension. The
      present data suggest that Brains Rule! Neuroscience Expositions are effective in
      improving communication and teaching skills among neuroscience professionals and
      contribute to professional stewardship by increasing motivation to participate in
      future informal education programs.

PMID- 17012207
TI  - Using literature and innovative assessments to ignite interest and cultivate
      critical thinking skills in an undergraduate neuroscience course.
AB  - Science education reform initiatives emphasize 1) the value of concepts over
      facts; 2) the benefits of open-ended, inquiry-based problem-solving rather than
      protocols leading to a single correct answer; and 3) the importance of a
      multidisciplinary approach to teaching that is not confined by departmental
      boundaries. Neuroscientists should be at the forefront of this movement by the
      very nature of the discipline we study. Neuroscience is a relatively new field
      that integrates diverse subjects (anatomy, physiology, pharmacology, molecular
      biology, computer science, and psychology) and experimental advances are
      constantly changing and expanding our understanding of brain function. How can we
      convey this excitement in the classroom? The project described in this article
      uses nonscientific literature to introduce a scientific topic of study. In
      addition, the multitask assignment requires the acquisition of content knowledge
      and the development of critical thinking skills. As students explore the topic
      from multiple perspectives, they recognize the interconnectedness of science and
      society and confront ethical and moral issues related to science. A comparison of
      exam scores, essay responses, engagement level, as well as students' own
      reflections, demonstrates that inclusion of the project does not sacrifice
      content knowledge, rather it enhances the overall learning process.

PMID- 17012208
TI  - Routes to research for novice undergraduate neuroscientists.
AB  - Undergraduate students may be attracted to science and retained in science by
      engaging in laboratory research. Experience as an apprentice in a scientist's
      laboratory can be effective in this regard, but the pool of willing scientists is
      sometimes limited and sustained contact between students and faculty is sometimes
      minimal. We report outcomes from two different models of a summer neuroscience
      research program: an Apprenticeship Model (AM) in which individual students
      joined established research laboratories, and a Collaborative Learning Model
      (CLM) in which teams of students worked through a guided curriculum and then
      conducted independent experimentation. Assessed outcomes included attitudes
      toward science, attitudes toward neuroscience, confidence with neuroscience
      concepts, and confidence with science skills, measured via pre-, mid-, and
      postprogram surveys. Both models elevated attitudes toward neuroscience,
      confidence with neuroscience concepts, and confidence with science skills, but
      neither model altered attitudes toward science. Consistent with the CLM design
      emphasizing independent experimentation, only CLM participants reported elevated
      ability to design experiments. The present data comprise the first of five yearly
      analyses on this cohort of participants; long-term follow-up will determine
      whether the two program models are equally effective routes to research or other
      science-related careers for novice undergraduate neuroscientists.

PMID- 17012209
TI  - Development of a neuroscience-oriented "methods" course for graduate students of
      pharmacology and toxicology.
AB  - To provide graduate students in pharmacology/toxicology exposure to, and cross
      training in, a variety of relevant laboratory skills, the Duquesne University
      School of Pharmacy developed a "methods" course as part of the core curriculum.
      Because some of the participating departmental faculty are neuroscientists, this
      course often applied cutting-edge techniques to neuroscience-based systems,
      including experiments with brain G protein-coupled receptors. Techniques covered
      by the course include animal handling and behavioral testing, bacterial and
      mammalian cell culture, enzyme-linked immunosorbent assay, western blotting,
      receptor binding of radioligands, plasmid DNA amplification and purification,
      reverse transcriptase-polymerase chain reaction, gel electrophoresis, and UV
      visible and fluorescence spectroscopy. The course also encompasses research
      aspects such as experimental design and record keeping, statistical analysis, and
      scientific writing. Students were evaluated via laboratory reports and
      examinations, and students in turn evaluated the course using a detailed exit
      survey. This course introduces the graduate student to many more techniques and
      approaches than can be provided by the traditional graduate "rotation" format
      alone and should serve as a template for graduate programs in many basic research
      disciplines.

PMID- 17012210
TI  - Rubrics: tools for making learning goals and evaluation criteria explicit for
      both teachers and learners.

PMID- 17012211
TI  - National and state standards in science and their potential influence on
      undergraduate science education.

PMID- 17012212
TI  - A ramble through the cell: how can we clear such a complicated trail?
AB  - The arrangement of course information in a logical sequence for molecular life
      science (MLS) courses remains a matter of some controversy, even within a single
      subdiscipline such as biochemistry. This is due to the explosion of knowledge,
      the latest bioinformatic revelations, and the observation that new discoveries
      sometimes reveal specific connections between previously disparate topics.
      However, the general outlines of biomedical information are in place, at least
      the knowledge that should be conveyed to undergraduates taking cell and molecular
      biology and biochemistry. Despite the increasing amount and complexity of the
      information to be presented, integration and unification are possible because the
      molecular reactions and interactions that underlie all life processes are coming
      into view: they are common to all cellular structural rearrangements, nucleic
      acid functions, and biochemical reactions, whether of plant or animal origin.
      Also, it is no longer possible to draw clear boundaries between cell biology,
      biochemistry, and molecular biology that would not violate the fundamental unity
      of our understanding. Therefore, an arrangement of content is proposed for a two
      semester course that aims to present a unified portrait of upper-division
      undergraduate MLS.

PMID- 17012213
TI  - Enhancing diversity in science: is teaching science process skills the answer?
AB  - The Biology Fellows Program at the University of Washington aims to enhance
      diversity in science by helping students succeed in the rigorous introductory
      biology classes and motivating them to engage in undergraduate research. The
      composite Scholastic Achievement Test scores and high school grade point averages
      of the Biology Fellows are comparable to those of students who are not in the
      program; however, they earn, on average, higher grades in introductory biology
      classes than non-Biology Fellows. Underrepresented minorities and disadvantaged
      students in the program also earn higher grades in the introductory biology
      classes than do their non-Biology Fellows counterparts. Analysis of the
      performance of Biology Fellows shows that the program assists students who are
      not proficient in certain science process skills and that students who lack these
      skills are at risk for failing introductory biology. This evaluation provides
      insight for designing programs that aim to enhance the performance of beginning
      students of biology, particularly for underrepresented minorities, who want to
      obtain a life science degree.

PMID- 17012214
TI  - Teaching cell and molecular biology for gender equity.
AB  - Science, technology, engineering, and math (STEM) fields, including cell biology,
      are characterized by the "leaky pipeline" syndrome in which, over time, women
      leave the discipline. The pipeline itself and the pond into which it empties may
      not be neutral. Explicating invisible norms, attitudes, and practices by
      integrating social studies of science into science education may be the necessary
      first step in helping female students persist in STEM disciplines. In 2003 and
      2004, a sophomore Cell and Molecular Biology course at Virginia Tech (Blacksburg,
      VA) was taught integrating social studies of science with standard material. The
      course was successfully implemented, teaching students factual content while
      increasing awareness of the cultures of science and their self-confidence in
      engaging with the subject. Course evaluation data indicated that females in
      particular perceived greater gains in logical thinking and problem-solving
      abilities than females in a traditional cell biology course. Consistent with K-12
      studies, males in this class were likely to view scientists as male only, whereas
      females viewed scientists as male and female. This pilot project demonstrates
      that social studies can be integrated successfully in a cell biology course.
      Longitudinal studies of this cohort of students will indicate whether this
      approach contributes to the retention of women in the field.

PMID- 17012215
TI  - From organelle to protein gel: a 6-wk laboratory project on flagellar proteins.
AB  - Research suggests that undergraduate students learn more from lab experiences
      that involve longer-term projects. We have developed a one-semester laboratory
      sequence aimed at sophomore-level undergraduates. In designing this curriculum,
      we focused on several educational objectives: 1) giving students a feel for the
      scientific research process, 2) introducing them to commonly used lab techniques,
      and 3) building skills in both data analysis and scientific writing. Over the
      course of the semester, students carry out two project-based lab experiences and
      write two substantial lab reports modeled on primary literature. Student
      assessment data indicate that this lab curriculum achieved these objectives. This
      article describes the first of these projects, which uses the biflagellate alga
      Chlamydomonas reinhardtii to introduce students to the study of flagellar
      motility, protein synthesis, microtubule polymerization, organelle assembly, and
      protein isolation and characterization.

PMID- 17012216
TI  - How golden is silence? Teaching undergraduates the power and limits of RNA
      interference.
AB  - It is hard and getting harder to strike a satisfying balance in teaching. Time
      dedicated to student-generated models or ideas is often sacrificed in an effort
      to "get through the syllabus." I describe a series of RNA interference (RNAi)
      experiments for undergraduate students that simultaneously explores fundamental
      concepts in gene regulation, develops cutting-edge laboratory skills, and
      embraces student-directed learning. Students design a small interfering RNA
      (siRNA) against luciferase, add it to cells expressing this gene, and then
      quantitatively assess the siRNA's effect on both intended and unintended targets,
      using a luciferase assay and a DNA microarray. Because both RNAi and microarray
      technologies are relatively new, with no clear consensus on their analysis or
      limitations, students are encouraged to explore different approaches to the
      design of their reagents and interpretations of their data. The ability to
      creatively formulate a hypothesis-driven experimental approach to a scientific
      question and to critically evaluate collected data is stressed. Equally
      important, this experiment emphasizes how modern scientific ideas emerge, are
      debated, tested, and decided.

PMID- 17012217
TI  - Animated cell biology: a quick and easy method for making effective, high-quality
      teaching animations.
AB  - There is accumulating evidence that animations aid learning of dynamic concepts
      in cell biology. However, existing animation packages are expensive and difficult
      to learn, and the subsequent production of even short animations can take weeks
      to months. Here I outline the principles and sequence of steps for producing high
      quality PowerPoint animations in less than a day that are suitable for teaching
      in high school through college/university. After developing the animation it can
      be easily converted to any appropriate movie file format using Camtasia Studio
      for Internet or classroom presentations. Thus anyone who can use PowerPoint has
      the potential to make animations. Students who viewed the approximately 3-min
      PowerPoint/Camtasia Studio animation "Calcium and the Dual Signalling Pathway"
      over 15 min scored significantly higher marks on a subsequent quiz than those who
      had viewed still graphics with text for an equivalent time. In addition, results
      from student evaluations provided some data validating the use of such animations
      in cell biology teaching with some interesting caveats. Information is also
      provided on how such animations can be modified or updated easily or shared with
      others who can modify them to fit their own needs.

PMID- 17012218
TI  - A simple and effective protein folding activity suitable for large lectures.
AB  - This article describes a simple and inexpensive hands-on simulation of protein
      folding suitable for use in large lecture classes. This activity uses a minimum
      of parts, tools, and skill to simulate some of the fundamental principles of
      protein folding. The major concepts targeted are that proteins begin as linear
      polypeptides and fold to three-dimensional structures, noncovalent interactions
      drive this folding process, and the final folded shape of a protein depends on
      its amino acid sequence. At the start of the activity, students are given pieces
      of insulated wire from which they each construct and fold their own polypeptide.
      This activity was evaluated in three ways. A random sample of student-generated
      polypeptides collected after the activity shows that most students were able to
      create an appropriate structure. After this activity, students (n = 154)
      completed an open-ended survey. Their responses showed that more than three
      quarters of the students learned one or more of the core concepts being
      demonstrated. Finally, a follow-up survey was conducted seven weeks after the
      activity; responses to this survey (n = 63) showed that a similar fraction of
      students still retained these key concepts. This activity should be useful in
      large introductory-level college biology or biochemistry lectures.

PMID- 17012219
TI  - Rethinking exams and letter grades: how much can teachers delegate to students?
AB  - In this article we report a 3-yr study of a large-enrollment Cell Biology course
      focused on developing student skill in scientific reasoning and data
      interpretation. Specifically, the study tested the hypothesis that converting the
      role of exams from summative grading devices to formative tools would increase
      student success in acquiring those skills. Traditional midterm examinations were
      replaced by weekly assessments administered under test-like conditions and
      followed immediately by extensive self, peer, and instructor feedback. Course
      grades were criterion based and derived using data from the final exam. To
      alleviate anxiety associated with a single grading instrument, students were
      given the option of informing the grading process with evidence from weekly
      assessments. A comparative analysis was conducted to determine the impact of
      these design changes on both performance and measures of student affect. Results
      at the end of each year were used to inform modifications to the course in
      subsequent years. Significant improvements in student performance and attitudes
      were observed as refinements were implemented. The findings from this study
      emphasized the importance of prolonging student opportunity and motivation to
      improve by delaying grade decisions, providing frequent and immediate performance
      feedback, and designing that feedback to be maximally formative and minimally
      punitive.

PMID- 17012220
TI  - Beverage-agarose gel electrophoresis: an inquiry-based laboratory exercise with
      virtual adaptation.
AB  - A wide range of literature and experience has shown that teaching methods that
      promote active learning, such as inquiry-based approaches, are more effective
      than those that rely on passive learning. Gel electrophoresis, one of the most
      common laboratory techniques in molecular biology, has a wide range of
      applications in the life sciences. As such, we chose it as a platform to expose
      high school and undergraduate students to the active process of scientific
      inquiry in general, while specifically teaching electrophoresis. First, we
      optimized DNA electrophoresis in the laboratory by using common beverages instead
      of standard media (e.g., Tris-based media). Second, we adapted this laboratory
      process of progressive optimization to a Web-based format in which students had
      to achieve all the same steps of optimization by performing serial
      electrophoreses. And third, we evaluated the use of this entirely Web-based
      virtual laboratory exercise in high school and undergraduate biology courses.
      Students learned fundamental and practical principles of electrophoresis, while
      experiencing the essential inquiry-based process of optimizing a technique, and
      they also enjoyed it. Our findings provide a readily accessible, inexpensive, and
      intriguing technique for teaching electrophoresis and the progressive
      optimization of a laboratory technique.

PMID- 17012221
TI  - TH1/TH2 cytokines: an easy model to study gene expression in immune cells.
AB  - This report describes a laboratory exercise that was incorporated into a Cell
      Biology and Molecular Biology advanced course. The exercise was made for a class
      size with eight students and was designed to reinforce the understanding of basic
      molecular biology techniques. Students used the techniques of reverse
      transcription and arginase activity measurement as well as nitric oxide
      determination to discover whether two specific genes were expressed by cytokine
      stimulated dendritic cells. The experiment served as the basis for discussing the
      importance of differential gene expression inside the eukaryotic cell and the
      importance of cytokines in the immune system.

PMID- 17012222
TI  - Gambogic acid-induced G2/M phase cell-cycle arrest via disturbing CDK7-mediated
      phosphorylation of CDC2/p34 in human gastric carcinoma BGC-823 cells.
AB  - Molecular mechanisms of cell-cycle arrest caused by gambogic acid (GA), a natural
      product isolated from the gamboge resin of Garcinia hanburryi tree, have been
      investigated using BGC-823 human gastric carcinoma cells as a model. Based on our
      3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazoliumbromide (MTT) assay and flow
      cytometric analysis, treatment of BGC-823 cells with growth suppressive
      concentrations of GA caused an irreversible arrest in the G(2)/M phase of the
      cell cycle. Western blot analysis demonstrated that GA-induced cell-cycle arrest
      in BGC-823 cells was associated with a significant decrease in CDC2/p34
      synthesis, which led to the accumulation of phosphorylated-Tyr(15) (inactive)
      form of CDC2/p34. Real-time PCR, western blot and kinase activity assays revealed
      that GA-induced reduction of CDC2/p34 expression was mediated through the
      inhibition of cyclin-dependent kinase (CDK)-activating kinase (CDK7/cyclin H)
      activity. In addition, GA-treated cells were shown to have a low level of CDK7
      kinase-phosphorylated-Thr(161) CDC2/p34 (active). Taken together, our results
      suggested that the inhibited proliferation of GA-treated BGC-823 cells was
      associated with the decreased production of CDK7 mRNA and protein, which in turn,
      resulted in the reduction of CDK7 kinase activity. The reduced CDK7 kinase
      activity is responsible for the inactivation of CDC2/p34 kinase and the
      irreversible G(2)/M phase cell-cycle arrest of human gastric carcinoma BGC-823
      cells.

PMID- 17012223
TI  - Constraints for genetic association studies imposed by attributable fraction and
      familial risk.
AB  - Candidate gene studies have become very popular but some of their implicit
      constraints, such as the familial risk and the population attributable fraction
      (PAF) conferred by the gene under study, are poorly understood. We model here
      these parameters for susceptibility genes in terms of genotype relative risk
      (GRR), allele frequency and statistical power in simulated genetic association
      studies, assuming 500 or 2000 case-control pairs and different modes of
      inheritance. The results show that the common association studies on genes with
      minor allele frequency >10% have sufficient power to detect disease-causing
      variants conferring PAFs >10%, which can be compared to known genes, such as
      BRCA1 with a PAF of 1.8%. Yet, common low-risk variants confer low familial
      relative risks (FRRs), typically <1.1. The models show that candidate gene
      studies may be able to identify genes conferring close to 100% of the PAF, but
      they may not explain the empirical FRRs. In order to explain FRRs, rare, high
      penetrant genes or interacting combinations of common variants need to be
      uncovered. However, the candidate gene studies for common alleles do not target
      this class of genes. The results may challenge the common disease-common variant
      hypothesis, which posits common variants with low GRRs and large PAFs, however
      failing to accommodate the empirical FRRs.

PMID- 17012224
TI  - Identification of kaempferol as an inhibitor of cigarette smoke-induced
      activation of the aryl hydrocarbon receptor and cell transformation.
AB  - The aryl hydrocarbon receptor (AHR) is a cytosolic receptor which upon activation
      by its agonists, translocates into the nucleus and forms a dimer with ARNT (aryl
      hydrocarbon nuclear translocator). The AHR/ARNT dimer regulates the expression of
      its target genes by binding to DNA recognition elements termed dioxin responsive
      elements (DREs). Many AHR agonists, like the polyaromatic hydrocarbons and
      polyhalogenated hydrocarbons are known human carcinogens. Human exposure to these
      compounds is common due to their presence in air pollution and cigarette smoke.
      Interestingly, many dietary constituents that have chemo preventative properties
      have been found to also act as antagonists of the AHR pathway. Thus, a
      chemopreventive approach that may be effective in decreasing the incidences of
      many human cancers may involve a dietary regimen that includes a number of these
      naturally occurring AHR antagonists. With this idea in mind, we have assayed the
      ability of 15 flavonoids to inhibit AHR activated reporter activity and selected
      kaempferol for further analysis. Kaempferol proved to be capable of inhibiting
      binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding
      complex and upregulation of the AHR target gene, CYP1A1. Using an in vitro
      paradigm of events that are thought to occur during cigarette-smoke-induced lung
      cancer, we found that kaempferol also inhibited the ability of cigarette smoke
      condensate to induce growth of immortalized lung epithelial (BEAS-2B) cells in
      soft agar. Taken together, these results illustrate the promise associated with
      the use of flavonoids, that inhibit both AHR signaling and the carcinogenic
      actions of AHR agonists, for chemopreventive purposes.

PMID- 17012225
TI  - Valproate induces widespread epigenetic reprogramming which involves
      demethylation of specific genes.
AB  - Valproate (VPA)(1) has been used for decades in the treatment of epilepsy, and is
      also effective as a mood stabilizer and in migraine therapy. It has been shown
      that VPA is also a histone deacetylase (HDAC) inhibitor. We have previously shown
      that VPA could trigger active demethylation of ectopically methylated transiently
      transfected DNA in HEK 293 cells. We therefore tested whether VPA treatment could
      bring about stable changes in the epigenome by causing changes in the state of
      DNA methylation of genomic DNA. Using a microarray gene expression analysis we
      identified the genes whose expression is induced by VPA treatment in HEK 293
      cells. We found that a subset of these genes could also be induced by the
      classical DNA methylation inhibitor 5-aza-2'-deoxy-cytidine (5-aza-CdR)
      suggesting that VPA can alter the state of expression of genes, which are stably
      suppressed by DNA methylation. We mapped the state of methylation of three of
      these genes, MELANOMA ANTIGEN B2 GENE (MAGEB2), METALLOPROTEINASE 2 (MMP2) and
      WIF1, which are involved in tumor growth and metastasis. A chromatin
      immunoprecipitation (ChIP) assay revealed that VPA treatment caused as expected a
      change in the state of acetylation of these genes. Our data supports the concept
      that chromatin acetylation and DNA methylation are found in a dynamic
      interrelation and that the consequences of HDAC inhibitors are not limited to
      changes in histone acetylation but that they also bring about a change in the
      state of modification of DNA. The implications of our results on the future
      therapeutic utilities of VPA in cancer will be discussed.

PMID- 17012226
TI  - Sorting nexin 10 induces giant vacuoles in mammalian cells.
AB  - Eukaryotic cells maintain a sophisticated network of intracellular membranous
      system to ensure the proper distribution and compartmentalization of cellular
      proteins critical for diverse functions such as cell division or cell-cell
      communication. Yet, little is known about the mechanism that regulates the
      homeostasis of this system. While analyzing the impact of sorting nexins on the
      trafficking of membrane type matrix metalloproteinases, we unexpectedly
      discovered that the expression of SNX10 induced the formation of giant vacuoles
      in mammalian cells. This vacuolizing activity is sensitive to mutations at the
      putative phosphoinositide 3-phosphate binding residue Arg(53). Domain-swap
      experiments with SNX3 demonstrate that the PX domain of SNX10 alone is
      insufficient to generate vacuoles and the downstream C-terminal domain is
      required for vacuolization. Brefeldin A, a chemical known to block the
      endoplasmic reticulum to Golgi transport, inhibited the vacuolization process.
      Together, these results suggest that SNX10 activity may be involved in the
      regulation of endosome homeostasis.

PMID- 17012227
TI  - Mechanistic insights and functional determinants of the transport cycle of the
      ascorbic acid transporter SVCT2. Activation by sodium and absolute dependence on
      bivalent cations.
AB  - We characterized the human Na(+)-ascorbic acid transporter SVCT2 and developed a
      basic model for the transport cycle that challenges the current view that it
      functions as a Na(+)-dependent transporter. The properties of SVCT2 are modulated
      by Ca(2+)/Mg(2+) and a reciprocal functional interaction between Na(+) and
      ascorbic acid that defines the substrate binding order and the transport
      stoichiometry. Na(+) increased the ascorbic acid transport rate in a cooperative
      manner, decreasing the transport K(m) without affecting the V(max), thus
      converting a low affinity form of the transporter into a high affinity
      transporter. Inversely, ascorbic acid affected in a bimodal and concentration
      dependent manner the Na(+) cooperativity, with absence of cooperativity at low
      and high ascorbic acid concentrations. Our data are consistent with a transport
      cycle characterized by a Na(+):ascorbic acid stoichiometry of 2:1 and a substrate
      binding order of the type Na(+):ascorbic acid:Na(+). However, SVCT2 is not
      electrogenic. SVCT2 showed an absolute requirement for Ca(2+)/Mg(2+) for
      function, with both cations switching the transporter from an inactive into an
      active conformation by increasing the transport V(max) without affecting the
      transport K(m) or the Na(+) cooperativity. Our data indicate that SVCT2 may
      switch between a number of states with characteristic properties, including an
      inactive conformation in the absence of Ca(2+)/Mg(2+). At least three active
      states can be envisioned, including a low affinity conformation at Na(+)
      concentrations below 20 mM and two high affinity conformations at elevated Na(+)
      concentrations whose Na(+) cooperativity is modulated by ascorbic acid. Thus,
      SVCT2 is a Ca(2+)/Mg(2+)-dependent transporter.

PMID- 17012228
TI  - Expression of SUMO-2/3 induced senescence through p53- and pRB-mediated pathways.
AB  - Three highly homologous small ubiquitin-related modifier (SUMO) proteins have
      been identified in mammals. Modifications of proteins by SUMO-1 have been shown
      to regulate transcription, nucleocytoplasmic transport, protein stability, and
      protein-protein interactions. Relative to SUMO-1, little is known about the
      functions of SUMO-2 or SUMO-3 (referred to as SUMO-2/3). Here, stable cell lines
      overexpressing processed forms of SUMO-2/3 (SUMO-2/3GG) as well as their non
      conjugatable derivatives, SUMO-2/3DeltaGG, were established. Cells overexpressing
      SUMO-2/3GG showed a premature senescence phenotype as revealed by cellular
      morphology and senescence-associated galactosidase activity. The senescence
      pathway protein p21 was up-regulated in cells overexpressing SUMO-2/3GG. In
      contrast, cells overexpressing non-conjugatable forms of SUMO-2/3DeltaGG showed
      neither an apparent senescent phenotype nor elevated p21. Both p53 and pRB were
      found to be modified by SUMO-2/3. Site-directed mutagenesis studies showed that
      Lys-386 of p53, the SUMO-1 modification site, is also the modification site for
      SUMO-2/3. In addition, H2O2 treatment of untransfected cells caused an increase
      in p53 sumoylation by SUMO-2/3, whereas that by SUMO-1 remained unchanged.
      Moreover, knocking down tumor suppressor proteins p53 or pRB using small
      interfering RNA significantly alleviated the premature senescence phenotypes in
      SUMO-2/3GG overexpressing cells. Together, our results reveal that p53 and pRB
      can be sumoylated by SUMO-2/3 in vivo, and such modification of p53 and pRB may
      play roles in premature senescence and stress response.

PMID- 17012230
TI  - Context-dependent dysregulation of transcription by mutant huntingtin.
AB  - Huntington disease (HD) is an adult-onset neurodegenerative disease caused by
      expansion of a polyglutamine (poly(Q) tract in the N-terminal region of
      huntingtin (htt). Although the precise mechanisms leading to neurodegeneration in
      HD have not been fully elucidated, transcriptional dysregulation has been
      implicated in disease pathogenesis. In HD, multiple N-terminal mutant htt
      fragments smaller than the first 500 amino acids have been found to accumulate in
      the nucleus and adversely affect gene transcription. It is unknown whether
      different htt fragments in the nucleus can differentially bind transcription
      factors and affect transcription. Here, we report that shorter N-terminal htt
      fragments, which are more prone to misfolding and aggregation, are more competent
      to bind Sp1 and inhibit its activity. These effects can be reversed by Hsp40, a
      molecular chaperone that reduces the misfolding of mutant htt. Our results
      provide insight into the beneficial effects of molecular chaperones and suggest
      that context dependent transcriptional dysregulation may contribute to
      differential toxicity of various N-terminal htt fragments.

PMID- 17012229
TI  - Interregulation of proton-gated Na(+) channel 3 and cystic fibrosis transmembrane
      conductance regulator.
AB  - Proton-gated Na(+) channels (ASIC) are new members of the epithelial sodium
      channel/degenerin gene family. ASIC3 mRNA has been detected in the homogenate of
      pulmonary tissues. However, whether ASIC3 is expressed in the apical membranes of
      lung epithelial cells and whether it regulates cystic fibrosis transmembrane
      conductance regulator (CFTR) function are not known at the present time. Using
      reverse transcription-PCR, we found that the ASIC3 mRNA was expressed in the
      human airway mucosal gland (Calu-3) and human airway epithelial (16HBE14o) cells.
      Indirect immunofluorescence microscopy revealed that ASIC3 was co-segregated with
      CFTR in the apical membranes of Calu-3 cells. Proton-gated, amiloride-sensitive
      short circuit Na(+) currents were recorded across Calu-3 monolayers mounted in an
      Ussing chamber. In whole-cell patch clamp studies, activation of CFTR channels
      with cAMP reduced proton-gated Na(+) current in Calu-3 cells from -154 +/- 28 to 
      33 +/- 16 pA (n = 5, p < 0.05) at -100 mV. On the other hand, cAMP-activated CFTR
      activity was significantly inhibited following constitutive activation of
      putative ASIC3 at pH 6.0. Immunoassays showed that both ASIC3 and CFTR proteins
      were expressed and co-immunoprecipitated mutually in Calu-3 cells. Similar
      results were obtained in human embryonic kidney 293T cells following transient co
      transfection of ASIC3 and CFTR. Our results indicate that putative CFTR and ASIC3
      channels functionally interact with each other, possibly via an intermolecular
      association. Because acidic luminal fluid in the cystic fibrosis airway and lung
      tends to stimulate ASIC3 channel expression and activity, the interaction of
      ASIC3 and CFTR may contribute to defective salt and fluid transepithelial
      transport in the cystic fibrotic pulmonary system.

PMID- 17012231
TI  - A revised model for AMP-activated protein kinase structure: The alpha-subunit
      binds to both the beta- and gamma-subunits although there is no direct binding
      between the beta- and gamma-subunits.
AB  - The 5'-AMP-activated protein kinase (AMPK) is a master sensor for cellular
      metabolic energy state. It is activated by a high AMP/ATP ratio and leads to
      metabolic changes that conserve energy and utilize alternative cellular fuel
      sources. The kinase is composed of a heterotrimeric protein complex containing a
      catalytic alpha-subunit, an AMP-binding gamma-subunit, and a scaffolding beta
      subunit thought to bind directly both the alpha- and gamma-subunits. Here, we use
      coimmunoprecipitation of proteins in transiently transfected cells to show that
      the alpha2-subunit binds directly not only to the beta-subunit, confirming
      previous work, but also to the gamma1-subunit. Deletion analysis of the alpha2
      subunit reveals that the C-terminal 386-552 residues are sufficient to bind to
      the beta-subunit. The gamma1-subunit binds directly to the alpha2-subunit at two
      interaction sites, one within the catalytic domain consisting of alpha2 amino
      acids 1-312 and a second within residues 386-552. Binding of the alpha2 and the
      gamma1-subunits was not affected by 400 mum AMP or ATP. Furthermore, we show that
      the beta-subunit C terminus is essential for binding to the alpha2-subunit but,
      in contrast to previous work, the beta-subunit does not bind directly to the
      gamma1-subunit. Taken together, this study presents a new model for AMPK
      heterotrimer structure where through its C terminus the beta-subunit binds to the
      alpha-subunit that, in turn, binds to the gamma-subunit. There is no direct
      interaction between the beta- and gamma-subunits.

PMID- 17012232
TI  - Apolipoprotein E and low density lipoprotein receptor-related protein facilitate
      intraneuronal Abeta42 accumulation in amyloid model mice.
AB  - The low density lipoprotein receptor-related protein (LRP) is highly expressed in
      the brain and has been shown to alter the metabolism of amyloid precursor protein
      and amyloid-beta peptide (Abeta) in vitro. Previously we developed mice that
      overexpress a functional LRP minireceptor (mLRP2) in their brains and crossed
      them to the PDAPP mouse model of Alzheimer disease. Overexpression of mLRP2 in 22
      month-old PDAPP mice with amyloid plaques increased a pool of carbonate-soluble
      Abeta in the brain and worsened memory-related behavior. In the current study, we
      examined the effects of mLRP2 overexpression on 3-month-old PDAPP mice that had
      not yet developed amyloid plaques. We found significantly higher levels of
      membrane-associated Abeta42 in the hippocampus of mice that overexpressed mLRP2.
      Using immunohistochemical methods, we observed significant intraneuronal Abeta42
      in the hippocampus and frontal cortex of PDAPP mice, which frequently co
      localized with the lysosomal marker LAMP-1. Interestingly, PDAPP mice lacking
      apolipoprotein E (apoE) had much less intraneuronal Abeta42. We also found that
      PC12 cells overexpressing mLRP2 cleared Abeta42 and Abeta40 more rapidly from
      media than PC12 cells transfected with the vector only. Preincubation of apoE3 or
      apoE4 with Abeta42 increased the rate of Abeta clearance, and this effect was
      partially blocked by receptor-associated protein. Our results support the
      hypothesis that LRP binds and endocytoses Abeta42 both directly and via apoE but
      that endocytosed Abeta42 is not completely degraded and accumulates in
      intraneuronal lysosomes.

PMID- 17012234
TI  - Id1 potentiates NF-kappaB activation upon T cell receptor signaling.
AB  - E2A and HEB are basic helix-loop-helix transcription factors that play important
      roles in T cell development. Expression of Id1, one of their inhibitors, severely
      impairs T cell development in transgenic mice. Aberrant activation of NF-kappaB
      transcription factors has been shown to contribute to the developmental defects,
      but it is not clear whether NF-kappaB activation is directly due to Id1
      expression or is secondary to an abnormal thymic environment in Id1 transgenic
      mice. Here, by using a T cell line model, we demonstrate that Id1 expression
      stimulates basal levels of NF-kappaB activity and further enhances NF-kappaB
      activation upon T cell receptor (TCR) signaling achieved by anti-CD3 and anti
      CD28 stimulation. Activation of NF-kappaB is partially mediated by the classical
      pathway involving the interaction between the regulatory subunit, NF-kappaB
      essential modulator (NEMO), and the catalytic subunit, IkappaB kinase beta.
      However, a NEMO-independent pathway also appears to be at play. Id1-potentiated
      activation of NF-kappaB leads to overproduction of cytokines such as tumor
      necrosis factor alpha and interferon-gamma in a T cell line as well as in
      thymocytes. Among members of the NF-kappaB family, c-Rel appears to be
      preferentially activated by Id1, especially during TCR stimulation. Consistently,
      c-rel deficiency diminishes tumor necrosis factor alpha and interferon-gamma
      expression induced by Id1 and TCR signaling.

PMID- 17012233
TI  - Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from
      Escherichia coli.
AB  - Acyl carrier proteins play a central role in metabolism by transporting
      substrates in a wide variety of pathways including the biosynthesis of fatty
      acids and polyketides. However, despite their importance, there is a paucity of
      direct structural information concerning the interaction of ACPs with enzymes in
      these pathways. Here we report the structure of an acyl-ACP substrate bound to
      the Escherichia coli fatty acid biosynthesis enoyl reductase enzyme (FabI), based
      on a combination of x-ray crystallography and molecular dynamics simulation. The
      structural data are in agreement with kinetic studies on wild-type and mutant
      FabIs, and reveal that the complex is primarily stabilized by interactions
      between acidic residues in the ACP helix alpha2 and a patch of basic residues
      adjacent to the FabI substrate-binding loop. Unexpectedly, the acyl-pantetheine
      thioester carbonyl is not hydrogen-bonded to Tyr(156), a conserved component of
      the short chain alcohol dehydrogenase/reductase superfamily active site triad.
      FabI is a proven target for drug discovery and the present structure provides
      insight into the molecular determinants that regulate the interaction of ACPs
      with target proteins.

PMID- 17012235
TI  - Tobacco etch virus mRNA preferentially binds wheat germ eukaryotic initiation
      factor (eIF) 4G rather than eIFiso4G.
AB  - The 5'-leader of tobacco etch virus (TEV) genomic RNA directs the efficient
      translation from the naturally uncapped viral RNA. The TEV 143-nt 5'-leader folds
      into a structure that contains two domains, each of which contains RNA
      pseudoknots. The 5'-proximal pseudoknot 1 (PK1) is necessary to promote cap
      independent translation (Zeenko, V., and Gallie, D. R. (2005) J. Biol. Chem. 280,
      26813-26824). During the translation initiation of cellular mRNAs, eIF4G
      functions as an adapter that recruits many of the factors involved in stimulating
      40 S ribosomal subunit binding to an mRNA. Two related but highly distinct eIF4G
      proteins are expressed in plants, animals, and yeast. The two plant eIF4G
      isoforms, referred to as eIF4G and eIFiso4G, differ in size (165 and 86 kDa,
      respectively) and their functional differences are still unclear. Although eIF4G
      is required for the translation of TEV mRNA, it is not known if eIF4G binds
      directly to the TEV RNA itself or if other factors are required. To determine
      whether binding affinity and isoform preference correlates with translational
      efficiency, fluorescence spectroscopy was used to measure the binding of eIF4G,
      eIFiso4G, and their complexes (eIF4F and eIFiso4F, respectively) to the TEV 143
      nt 5'-leader (TEV1-143) and a shorter RNA that contained PK1. A mutant (i.e. S1
      3) in which the stem of PK1 was disrupted resulting in impaired cap-independent
      translation, was also tested. These studies demonstrate that eIF4G binds TEV1-143
      and PK1 RNA with approximately 22-30-fold stronger affinity than eIFiso4G. eIF4G
      and eIF4F bind TEV1-143 with similar affinity, whereas eIFiso4F binds with
      approximately 6-fold higher affinity than eIFiso4G. The binding affinity of
      eIF4G, eIF4F, and eIFiso4G to S1-3 was reduced by 3-5-fold, consistent with the
      reduction in the ability of this mutant to promote cap-independent translation.
      Temperature-dependent binding studies revealed that binding of the TEV 5'-leader
      to these initiation factors has a large entropic contribution. Overall, these
      results demonstrate the first direct interaction of eIF4G with the TEV 5'-leader
      in the absence of other initiation factors. These data correlate well with the
      observed translational data and provide more detailed information on the
      translational strategy of potyviruses.

PMID- 17012236
TI  - A novel mechanism of tissue inhibitor of metalloproteinases-1 activation by
      interleukin-1 in primary human astrocytes.
AB  - Reactive astrogliosis is the gliotic response to brain injury with activated
      astrocytes and microglia being the major effector cells. These cells secrete
      inflammatory cytokines, proteinases, and proteinase inhibitors that influence
      extracellular matrix (ECM) remodeling. In astrocytes, the expression of tissue
      inhibitor of metalloproteinases-1 (TIMP-1) is up-regulated by interleukin-1 (IL
      1), which is a major neuroinflammatory cytokine. We report that IL-1 activates
      TIMP-1 expression via both the IKK/NF-kappaB and MEK3/6/p38/ATF-2 pathways in
      astrocytes. The activation of the TIMP-1 gene can be blocked by using
      pharmacological inhibitors, including BAY11-7082 and SB202190, overexpression of
      the dominant-negative inhibitor of NF-kappaB (IkappaBalphaSR), or by the knock
      down of p65 subunit of NF-kappaB. Binding of activated NF-kappaB (p50/p65
      heterodimer) and ATF-2 (homodimer) to two novel regulatory elements located -2.7
      and -2.2 kb upstream of the TIMP-1 transcription start site, respectively, is
      required for full IL-1-responsiveness. Mutational analysis of these regulatory
      elements and their weak activity when linked to the minimal tk promoter suggest
      that cooperative binding is required to activate transcription. In contrast to
      astrocytes, we observed that TIMP-1 is expressed at lower levels in gliomas and
      is not regulated by IL-1. We provide evidence that the lack of TIMP-1 activation
      in gliomas results from either dysfunctional IKK/NF-kappaB or MEK3/6/p38/ATF-2
      activation by IL-1. In summary, we propose a novel mechanism of TIMP-1
      regulation, which ensures an increased supply of the inhibitor after brain
      injury, and limits ECM degradation. This mechanism does not function in gliomas,
      and may in part explain the increased invasiveness of glioma cells.

PMID- 17012237
TI  - Activation of muscle-specific receptor tyrosine kinase and binding to
      dystroglycan are regulated by alternative mRNA splicing of agrin.
AB  - Agrin induces the aggregation of postsynaptic proteins at the neuromuscular
      junction (NMJ). This activity requires the receptor-tyrosine kinase MuSK. Agrin
      isoforms differ in short amino acid stretches at two sites, called A and B, that
      are localized in the two most C-terminal laminin G (LG) domains. Importantly,
      agrin isoforms greatly differ in their activities of inducing MuSK
      phosphorylation and of binding to alpha-dystroglycan. By using site-directed
      mutagenesis, we characterized the amino acids important for these activities of
      agrin. We find that the conserved tripeptide asparagineglutamate-isoleucine in
      the eight-amino acid long insert at the B-site is necessary and sufficient for
      full MuSK phosphorylation activity. However, even if all eight amino acids were
      replaced by alanines, this agrin mutant still has significantly higher MuSK
      phosphorylation activity than the splice version lacking any insert. We also show
      that binding to alpha-dystroglycan requires at least two LG domains and that
      amino acid inserts at the A and the B splice sites negatively affect binding.

PMID- 17012238
TI  - The N-terminal lobes of both regulatory light chains interact with the tail
      domain in the 10 S-inhibited conformation of smooth muscle myosin.
AB  - In the presence of ATP, unphosphorylated smooth muscle myosin can form a
      catalytically inactive monomer that sediments at 10 Svedbergs (10 S). The tail of
      10 S bends into thirds and interacts with the regulatory domain. ADP-P(i) is
      "trapped" at the active site, and consequently the ATPase activity is extremely
      low. We are interested in the structural basis for maintenance of this off state.
      Our prior photocross-linking work with 10 S showed that tail residues 1554-1583
      are proximal to position 108 in the C-terminal lobe of one of the two regulatory
      light chains ( Olney, J. J., Sellers, J. R., and Cremo, C. R. (1996) J. Biol.
      Chem. 271, 20375-20384 ). These data suggested that the tail interacts with only
      one of the two regulatory light chains. Here we present data, using a photocross
      linker on position 59 on the N-terminal lobe of the regulatory light chain (RLC),
      demonstrating that both regulatory light chains of a single molecule can cross
      link to the light meromyosin portion of the tail. Mass spectrometric data show
      four specific cross-linked regions spanning residues 1428-1571 in the light
      meromyosin portion of the tail, consistent with cross-linking two RLC to one
      light meromyosin. In addition, we find that position 59 can cross-link internally
      to residues 42-45 within the same RLC subunit. The internal cross-link only forms
      in 10 S and not in unphosphorylated heavy meromyosin (lacking the light
      meromyosin), suggesting a structural rearrangement within the RLC attributed to
      the interaction of the tail with the head.

PMID- 17012239
TI  - The exchange factor and diacylglycerol receptor RasGRP3 interacts with dynein
      light chain 1 through its C-terminal domain.
AB  - RasGRP3 is an exchange factor for Ras-like small GTPases that is activated in
      response to the second messenger diacylglycerol. As with other diacylglycerol
      receptors, RasGRP3 is redistributed upon diacylglycerol or phorbol ester binding.
      Several factors are important in determining the pattern of translocation,
      including the potency of the diacylglycerol analog, the affinity of the receptor
      for phospholipids, and in some cases, protein-protein interactions. However,
      little is known about the mechanisms that play a role in RasGRP3 redistribution
      aside from the nature of the ligand. To discover potential protein binding
      partners for RasGRP3, we screened a human brain cDNA library using a yeast two
      hybrid approach. We identified dynein light chain 1 as a novel RasGRP3
      interacting protein. The interaction was confirmed both in vitro and in vivo and
      required the C-terminal domain encompassing the last 127 amino acids of RasGRP3.
      A truncated mutant form of RasGRP3 that lacked this C-terminal domain was unable
      to interact with dynein light chain 1 and displayed a dramatically altered
      subcellular localization, with a strong reticular distribution and perinuclear
      and nuclear localization. These findings suggest that dynein light chain 1
      represents a novel anchoring protein for RasGRP3 that may regulate subcellular
      localization of the exchange factor and, as such, may participate in the
      signaling mediated by diacylglycerol through RasGRP3.

PMID- 17012240
TI  - Prion protein helix1 promotes aggregation but is not converted into beta-sheet.
AB  - Prion diseases are caused by the aggregation of the native alpha-helical prion
      protein PrP(C) into its pathological beta-sheet-rich isoform PrP(Sc). In current
      models of PrP(Sc), helix1 is assumed to be preferentially converted into beta
      sheet during aggregation of PrP(C). This was supported by the NMR structure of
      PrP(C) since, in contrast to the isolated helix1, helix2 and helix3 are connected
      by a small loop and are additionally stabilized by an interhelical disulfide
      bond. However, helix1 is extremely hydrophilic and has a high helix propensity.
      This prompted us to investigate the role of helix1 in prion aggregation using
      humPrP(23-159) including helix1 (144-156) compared with the C-terminal-truncated
      isoform humPrP(23-144) corresponding to the pathological human stop mutations
      Q160Stop and Y145Stop, respectively. Most unexpectedly, humPrP(23-159) aggregated
      significantly faster compared with the truncated fragment humPrP(23-144), clearly
      demonstrating that helix1 is involved in the aggregation process. However, helix1
      is not resistant to digestion with proteinase K in fibrillar humPrP(23-159),
      suggesting that helix1 is not converted to beta-sheet. This is confirmed by
      Fourier transformation infrared spectroscopy since there is almost no difference
      in beta-sheet content of humPrP(23-159) fibrils compared with humPrP(23-144). In
      conclusion, we provide strong direct evidence that in contrast to earlier
      assumptions helix1 is not converted into beta-sheet during aggregation of PrP(C)
      to PrP(Sc).

PMID- 17012241
TI  - Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in
      neuronal oxidative and DNA damage response.
AB  - Cyclooxygenase-2 (COX-2) has been implicated in neuronal survival and death.
      However, the precise regulatory mechanisms involved in COX-2 function are
      unclear. In the present study we found that COX-2 is induced in response to
      glutathione depletion-induced oxidative stress in primary cortical neurons. Two
      proximal specific Sp1 and Sp3 binding sites are responsible for the COX-2
      promoter activity under normal as well as oxidative stress conditions through
      enhanced Sp1 and Sp3 DNA binding activity. Site-directed mutagenesis confirmed
      that -268/-267 positions serve as specific Sp1 and Sp3 recognition sites under
      oxidative stress. Enforced expression of Sp1 and Sp3 using HSV vectors increased
      the promoter activity, transcription, and protein level of COX-2 in cortical
      neurons. The dominant negative form of Sp1 abrogated the oxidative stress-induced
      promoter activity and expression of COX-2. We also demonstrated that adenovirus
      mediated COX-2 gene delivery protected neurons from DNA damage induced by
      oxidative, genotoxic, and excitotoxic stresses and by ischemic injury. Moreover,
      COX-2(-/-) cortical neurons were more susceptible to DNA damage-induced cell
      death. These results indicate that in primary neurons Sp1 and Sp3 play an
      essential role in the modulation of COX-2 transcription, which mediates neuronal
      homeostasis and survival by preventing DNA damage in response to neuronal stress.

PMID- 17012242
TI  - A polymorphic glucocorticoid receptor in a mouse population may explain inherited
      altered stress response and increased anxiety-type behaviors.
AB  - A polymorphic glucocorticoid receptor (GR(Qn)) with an expanded CAG track and two
      silent mutations, when compared with the sequence of other isoform (GR(wt)), is
      found in two outbred mouse lines that were produced by selection for high (SH) or
      low (SL) stress response from high or low heat loss lines of mice, respectively.
      The GR(Qn) allele, which is also found in 5 of 16 commonly used inbred mouse
      lines, had a much higher frequency in SL mice; the GR(wt/wt) was found only in
      the SH line. Both GR(Qn/Qn) and GR(wt/Qn) mice had a much weaker corticosterone
      response to stress than the GR(wt/wt) mice. Assessment of open field activity
      revealed that GR(Qn/Qn) and GR(wt/Qn) mice exhibited significantly lower velocity
      and locomotor activity, less time in the center, and much longer duration in
      corner zones than the GR(wt/wt) mice. The increased anxiety-type behaviors of the
      GR(Qn/Qn) and GR(wt/Qn) mice were confirmed by the "elevated plus maze" test in
      which GR(Qn/Qn) and GR(wt/Qn) mice spent significantly less time in the "open
      arm" and longer duration in the "closed arm," than GR(wt/wt) mice. These results
      suggest this GR polymorphism plays a role in complex mechanisms leading to lower
      corticosterone response to stress, and may also be associated with decreased
      locomotive and increased anxiety-type behaviors in mice.

PMID- 17012243
TI  - Rickettsia as obligate and mycetomic bacteria.
AB  - Rickettsiae are well known as intracellular pathogens of animals, humans, and
      plants and facultative and unorganized symbionts of invertebrates. No close
      relative of mitochondria has yet been associated with nutritional or
      developmental dependency of its host cell or organism. We have found a mycetomic
      Rickettsia that is a strict obligatory symbiont of the parthenogenetic booklouse
      Liposcelis bostrychophila (Psocoptera). These rickettsiae show an evolutionary
      transition from a solitary to a primary mycetomic bacterium adapted to the
      development of its host. These intracellular and intranuclear bacteria reside in
      specialized cells in several tissues. Their distribution changes markedly with
      the development of their host. The most advanced phenotype is a paired mycetome
      in the abdomen, described for the first time for Rickettsia and this host order.
      The mycetomic rickettsiae of two parthenogenetic book lice species are in the
      spotted fever group and in the basal limoniae group. While mycetomic bacteria are
      well known for their metabolic or light-emitting functions, these rickettsiae
      have an essential role in the early development of the oocyte. Removal of the
      Rickettsia stops egg production and reproduction in the book louse. In two
      phylogenetically distant psocopteran species, Rickettsia are shown to be
      associated with four transitional stages from free bacteria, infected cells,
      through single mycetocytes to organ-forming mycetomes.

PMID- 17012244
TI  - Regulation of transferrin recycling kinetics by PtdIns[4,5]P2 availability.
AB  - Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) is a phosphoinositide
      involved in a variety of cellular functions, including signal transduction,
      organelle trafficking, and actin dynamics. Although the role of PtdIns[4,5]P2 in
      endocytosis is well established, the precise trafficking steps relying on normal
      PtdIns[4,5]P2 balance in the endosomal pathway have not yet been elucidated. Here
      we show that decrease in intracellular PtdIns[4,5]P2 levels achieved by the
      overexpression of the 5-phosphatase domain of synaptojanin 1 or by siRNA knock
      down of PIP5Ks expression lead to severe defects in the internalization of
      transferrin as well as in the recycling of internalized transferrin back to the
      cell surface in COS-7 cells. These defects suggest that PtdIns[4,5]P2
      participates in multiple trafficking and/or sorting events during endocytosis.
      Coexpression of the PtdIns[4,5]P2 synthesizing enzyme, PIP5KI gamma, was able to
      rescue these endocytic defects. Furthermore, decreased levels of PtdIns[4,5]P2
      caused delays in rapid and slow membrane recycling pathways as well as a severe
      backup of endocytosed membrane. Taken together, our results demonstrate that
      PtdIns[4,5]P2 availability regulates multiple steps in the endocytic cycle in non
      neuronal cells.

PMID- 17012245
TI  - Science in the Middle East: "yes, you have found it".

PMID- 17012246
TI  - Science in Greece: from the age of Hippocrates to the age of the genome.

PMID- 17012247
TI  - Proprotein convertases: lessons from knockouts.
AB  - The physiological role of the subtilisin/kexin-like proprotein convertases (PCs)
      in rodents has been examined through the use of knockout mice. This review will
      summarize the major in vivo defects that result from the disruption of the
      expression of their genes. This includes abnormal embryonic development, hormonal
      disorder, infertility, and/or modified lipid/sterol metabolism. Members of the PC
      family play a central role in the processing of various protein precursors
      ranging from hormones and growth factors to bacterial toxins and viral
      glycoproteins. Proteolysis occurring at basic residues is mediated by the basic
      amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4,
      PC4, PC5/6, and PC7. In contrast, proteolysis at nonbasic residues is performed
      by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified
      neural apoptosis-regulated convertase-1 (PCSK9/NARC-1). In addition to their
      requirement for many physiological processes, these enzymes are also involved in
      various pathologies such as cancer, obesity, diabetes, lipid disorders,
      infectious diseases, atherosclerosis and neurodegenerative diseases.

PMID- 17012248
TI  - Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted
      evolution with Siglec-5 in primates.
AB  - Immune receptors that show high mutual sequence similarity and have antagonizing
      signaling properties are called paired receptors, and are believed to fine-tune
      immune responses. Siglecs are sialic acid-recognizing receptors of the
      immunoglobulin (Ig) superfamily expressed on immune cells. Human Siglec-5,
      encoded by SIGLEC5 gene, has four extracellular Ig-like domains and a cytosolic
      inhibitory motif. We discovered human Siglec-14 with three Ig-like domains,
      encoded by the SIGLEC14 gene, adjacent to SIGLEC5. Human Siglec-14 has almost
      complete sequence identity with human Siglec-5 at the first two Ig-like domains,
      shows a glycan binding preference similar to that of human Siglec-5, and
      associates with the activating adapter protein DAP12. Thus, Siglec-14 and Siglec
      5 appear to be the first glycan binding paired receptors. Near-complete sequence
      identity of the amino-terminal part of human Siglec-14 and Siglec-5 indicates
      partial gene conversion between SIGLEC14 and SIGLEC5. Remarkably, SIGLEC14 and
      SIGLEC5 in other primates also show evidence of gene conversions within each
      lineage. Evidently, balancing the interactions between Siglec-14, Siglec-5 and
      their common ligand(s) had selective advantage during the course of evolution.
      The "essential arginine" critical for sialic acid recognition in both Siglec-14
      and Siglec-5 is present in humans but mutated in almost all great ape alleles.

PMID- 17012249
TI  - Evidence that aquaporin 1 is a major pathway for CO2 transport across the human
      erythrocyte membrane.
AB  - We report here the application of a previously described method to directly
      determine the CO2 permeability (P(CO2)) of the cell membranes of normal human red
      blood cells (RBCs) vs. those deficient in aquaporin 1 (AQP1), as well as AQP1
      expressing Xenopus laevis oocytes. This method measures the exchange of (18)O
      between CO2, HCO3(-), and H2O in cell suspensions. In addition, we measure the
      alkaline surface pH (pH(S)) transients caused by the dominant effect of entry of
      CO2 vs. HCO3(-) into oocytes exposed to step increases in [CO2]. We report that
      1) AQP1 constitutes the major pathway for molecular CO2 in human RBCs; lack of
      AQP1 reduces P(CO2) from the normal value of 0.15 +/- 0.08 (SD; n=85) cm/s by 60%
      to 0.06 cm/s. Expression of AQP1 in oocytes increases P(CO2) 2-fold and doubles
      the alkaline pH(S) gradient. 2) pCMBS, an inhibitor of the AQP1 water channel,
      reduces P(CO2) of RBCs solely by action on AQP1 as it has no effect in AQP1
      deficient RBCs. 3) P(CO2) determinations of RBCs and pH(S) measurements of
      oocytes indicate that DIDS inhibits the CO2 pathway of AQP1 by half. 4) RBCs have
      at least one other DIDS-sensitive pathway for CO2. We conclude that AQP1 is
      responsible for 60% of the high P(CO2) of red cells and that another, so far
      unidentified, CO2 pathway is present in this membrane that may account for at
      least 30% of total P(CO2).

PMID- 17012250
TI  - Probing the human kinome for kinases involved in pancreatic cancer cell survival
      and gemcitabine resistance.
AB  - Except for gemcitabine, chemotherapeutic agents are ineffective with pancreatic
      adenocarcinoma because this cancer is resistant to apoptosis induction.
      Involvement of specific kinases in such resistance is likely. We developed a
      systematic strategy to screen the human kinome and select kinases whose
      inhibition in pancreatic cancer cells can increase 1) spontaneous apoptosis or 2)
      gemcitabine-induced apoptosis. The pancreatic adenocarcinoma cell line MiaPaCa-2
      was transfected with 645 pairs of siRNAs directed to all human kinases. The same
      experiment was conducted in cells treated with 150 microM gemcitabine. Apoptosis
      was measured after 2 days and the results were normalized for cell viability. A
      panel of 56 kinases whose inhibition increased spontaneous apoptosis by at least
      50% was established. Ten of them gave similar results on Panc1 and BxPC3
      pancreatic adenocarcinoma cell lines. A panel of 83 kinases whose inhibition
      increased gemcitabine-induced apoptosis by 50% or more was also established.
      Twelve kinases appeared in both panels. A cumulative increase in apoptosis was
      observed when inhibiting simultaneously several kinases. Such a systematic
      approach allowed characterization of all kinases involved in pancreatic cancer
      cell survival and resistance to gemcitabine. Inhibitors of these kinases, used
      alone or in combination, might improve the treatment of pancreatic
      adenocarcinoma.

PMID- 17012251
TI  - Pivotal role of integrin alpha5beta1 in hypotonic stress-induced responses of
      human endothelium.
AB  - We have previously reported that both hypotonic stress (HTS) and lysophosphatidic
      acid (LPA) induce ATP release and a transient reorganization of actin through
      sequential activation of RhoA/Rho-kinase and focal adhesion kinase F-actin
      (FAK)/paxillin in human umbilical cord vein endothelial cells (HUVECs). LPA is
      known to induce the activation of RhoA via its specific receptors, but the
      mechanisms by which HTS initiates these intracellular signals are not known. The
      present study aimed to identify the molecule(s) that are unique to the sensing
      and/or transducing the mechanical stress. Reverse transcriptase-polymerase chain
      reaction revealed the expression of several integrin subunits in HUVECs. Anti
      integrin alpha5beta1 antibody (Ab), but not anti-integrin alpha2, alpha6, alpha
      v, or beta4 antibodies, inhibited HTS-induced RhoA translocation, tyrosine
      phosphorylation of FAK and paxillin, ATP release, and actin reorganization.
      However, the LPA-induced ATP release and actin reorganization were not inhibited
      by any of these anti-integrin antibodies, indicating that integrin alpha5beta1
      plays a pivotal role in the HTS-induced but not in the LPA-induced responses. It
      is therefore reasonable to assume that this particular subtype of integrin is
      involved in the initiation of the responses induced by mechanical stimuli in
      HUVECs.

PMID- 17012252
TI  - Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human
      astrocytes and astrocytoma cells.
AB  - Autosomal dominant Parkinson disease (PD) is caused by duplication or
      triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T
      mutations. The mechanisms are unknown. Reactive astrocytes in the substantia
      nigra of PD and MPTP-treated monkeys display high levels of the inflammatory
      mediator intercellular adhesion molecule-1 (ICAM-1), indicating that chronic
      inflammation contributes to the degeneration. Here we report that alpha-synuclein
      strongly stimulates human astrocytes as well as human U-373 MG astrocytoma cells
      to up-regulate both interleukin (IL)-6 and ICAM-1 (ED50=5 microg ml(-1)). The
      mutated forms are more potent stimulators than wild-type (WT) alpha-synuclein in
      these assays. We demonstrate by immunoblotting analysis that this up-regulation
      is associated with activation of the major mitogen-activated protein kinase
      (MAPK) pathways. It is also attenuated by PD 98059, an inhibitor of the
      MAPK/extracellular-regulated kinase kinase MEK1/2, SP 600125, an inhibitor of c
      Jun N-terminal kinase (JNK), and SB 202190, an inhibitor of p38 MAPK. The
      inhibitory effects on human astrocytes have IC50 values of 2, 5, and 1.5 microM
      respectively. We hypothesize that the neuroinflammation stimulated by release of
      an excess of normal alpha-synuclein or by release of its mutated forms can be
      involved in the pathobiology of PD.

PMID- 17012253
TI  - Therapeutic levels of aspirin and salicylate directly inhibit a model of
      angiogenesis through a Cox-independent mechanism.
AB  - A range of antineoplastic properties is attributed to aspirin, thought to be due
      to inhibition of cyclooxygenase (Cox) enzymes in tumor cells. One important
      outcome is that by reducing angiogenic factor secretion by cancer cells, aspirin
      also inhibits angiogenesis, thereby restricting tumor growth. However, aspirin
      may also have direct effects on endothelial cells to regulate angiogenesis. Our
      aim was to quantitate these effects and determine whether they occurred through
      inhibiting Cox enzymes. The effects of aspirin, salicylate (the natural
      deacetylated form of aspirin), and the selective Cox inhibitors SC560 and
      Celecoxib on endothelial cell proliferation, viability, and angiogenesis were
      compared. Therapeutic aspirin concentrations (0.5 mM) had no detectable effect on
      endothelial cell viability or proliferation but caused a striking reduction in
      tubule formation in a three-dimensional collagen angiogenesis assay. This was
      also seen with equimolar concentrations of salicylate, while selective Cox
      inhibitors did not inhibit angiogenesis in this assay either alone or in
      combination. Furthermore, high doses of aspirin or salicylate (5 mM), well above
      therapeutic plasma concentrations, lead to endothelial cell apoptosis. We
      conclude that aspirin, at therapeutic concentrations, directly inhibits
      angiogenesis via a Cox-independent mechanism, which may significantly contribute
      to its neoplastic protective effects.

PMID- 17012254
TI  - What the buzz was all about: superfast song muscles rattle the tymbals of male
      periodical cicadas.
AB  - Male cicadas produce mating calls by oscillating a pair of superfast tymbal
      muscles in their anterior abdominal cavity that pull on and buckle stiff-ribbed
      cuticular tymbal membranes located beneath the folded wings. The functional
      anatomy and rattling of the tymbal organ in 17 yr periodical cicada, Magicicada
      cassini (Brood X), were revealed by high-resolution microcomputed tomography,
      magnetic resonance imaging, electron microscopy, and laser vibrometry to
      understand the mechanism of sound production in these insects. Each 50 Hz muscle
      contraction yielded five to six stages of rib buckling in the tymbal, and a small
      release of muscle tension resulted in a rapid recovery due to the spring-loaded
      nature of the stiff ribs in the resilin-rich tymbal. The tymbal muscle sarcomeres
      have thick and thin filaments that are 30% shorter than those in flight muscles,
      with Z-bands that were thicker and configured into novel perforated hexagonal
      lattices. Caffeine-treated fibers supercontracted by allowing thick filaments to
      traverse the Z-band through its open lattice. This superfast sonic muscle
      illustrates design features, especially the matching hexagonal symmetry of the
      myofilaments and the perforated Z-band that contribute to high-speed
      contractions, long endurance, and potentially supercontraction needed for
      producing enduring mating songs and choruses.

PMID- 17012255
TI  - Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a
      fatty acid synthase inhibitor.
AB  - Orlistat, an antiobesity drug, is cytostatic and cytotoxic to tumor cells. The
      antitumor activity of orlistat can be attributed to its ability to inhibit the
      thioesterase domain of fatty acid synthase (FAS). The objective of the present
      study was to test the effect of orlistat on endothelial cell proliferation and
      angiogenesis. Orlistat inhibits endothelial cell FAS, blocks the synthesis of
      fatty acids, and prevents endothelial cell proliferation. More significantly,
      orlistat inhibits human neovascularization in an ex vivo assay, which suggests
      that it may be useful as an antiangiogenic drug. The mechanism of these effects
      can be traced to the fact that orlistat prevents the display of the vascular
      endothelial growth factor (VEGF) receptor (VEGFR2/KDR/Flk1) on the endothelial
      cell surface. Thus, orlistat is an antiangiogenic agent with a novel mechanism of
      action.

PMID- 17012256
TI  - Biological characterization of gene response in Rpe65-/- mouse model of Leber's
      congenital amaurosis during progression of the disease.
AB  - RPE65 is the retinal isomerase essential for conversion of all-trans-retinyl
      ester to 11-cis-retinol in the visual cycle. Leber's congenital amaurosis (LCA),
      an autosomal recessive form of RP resulting in blindness, is commonly caused by
      mutations in the Rpe65 gene. Whereas the molecular mechanisms by which these
      mutations contribute to retinal disease remain largely unresolved, affected
      patients show marked RPE damage and photoreceptor degeneration. We evaluated gene
      expression in Rpe65-/- mouse model of LCA before and at the onset of
      photoreceptor cell death in 2, 4, and 6 month old animals. Microarray analysis
      demonstrates altered expression of genes involved in phototransduction, apoptosis
      regulation, cytoskeleton organization, and extracellular matrix (ECM)
      constituents. Cone-specific phototransduction genes are strongly decreased,
      reflecting early loss of cones. In addition, remaining rods show modified
      expression of genes encoding components of the cytoskeleton and ECM. This may
      affect rod physiology and interaction with the adjacent RPE and lead to loss of
      survival signals, as reflected by the alteration of apoptosis-related genes
      Together, these results suggest that RPE65 defect triggers an overall remodeling
      of the neurosensitive retina that may, in turn, disrupt photoreceptor homeostasis
      and induce apoptosis signaling cascade toward retinal cell death.

PMID- 17012257
TI  - Detection of novel intracellular alpha-synuclein oligomeric species by
      fluorescence lifetime imaging.
AB  - Oligomerization and aggregation of alpha-synuclein molecules are believed to play
      a major role in neuronal dysfunction and loss in Parkinson's disease (PD) and
      dementia with Lewy bodies. However, alpha-synuclein oligomerization and
      aggregation have been detected only indirectly in cells using detergent
      extraction methods. Here, we show for the first time intracellular alpha
      synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms
      of alpha-synuclein homomeric interactions were detected: an antiparallel amino
      terminus-carboxyl terminus interaction between alpha-synuclein molecules, and a
      close amino terminus-carboxy terminus interaction within single alpha-synuclein
      molecules. Coexpression of the chaperone protein Hsp70, which can block alpha
      synuclein toxicity in several systems, causes alpha-synuclein to adopt a
      different, open conformation, but Hsp70 does not alter alpha-synuclein-alpha
      synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be
      explained by its chaperone activity on alpha-synuclein molecules, rather than
      alteration of alpha-synuclein-alpha-synuclein interactions.

PMID- 17012259
TI  - Kallikrein-mediated proteolysis regulates the antimicrobial effects of
      cathelicidins in skin.
AB  - The presence of cathelicidin antimicrobial peptides provides an important
      mechanism for prevention of infection against a wide variety of microbial
      pathogens. The activity of cathelicidin is controlled by enzymatic processing of
      the proform (hCAP18 in humans) to a mature peptide (LL-37 in human neutrophils).
      In this study, elements important to the processing of cathelicidin in the skin
      were examined. Unique cathelicidin peptides distinct from LL-37 were identified
      in normal skin. Through the use of selective inhibitors, SELDI-TOF-MS, Western
      blot, and siRNA, the serine proteases stratum corneum tryptic enzyme (SCTE,
      kallikrein 5) and stratum corneum chymotryptic protease (SCCE, kallikrein 7) were
      shown to control activation of the human cathelicidin precursor protein hCAP18
      and also influence further processing to smaller peptides with alternate
      biological activity. The importance of this serine protease activity to
      antimicrobial activity in vivo was illustrated in SPINK5-deficient mice that lack
      the serine protease inhibitor LEKTI. Epidermal extracts of these animals show a
      significant increase in antimicrobial activity compared with controls, and
      immunoabsorption of cathelicidin diminished antimicrobial activity. These
      observations demonstrate that the balance of proteolytic activity at an
      epithelial interface will control innate immune defense.

PMID- 17012258
TI  - Bactericidal/permeability-increasing protein's signaling pathways and its retinal
      trophic and anti-angiogenic effects.
AB  - Bactericidal/permeability-increasing protein (BPI) was originally identified as a
      lipopolysaccharide (LPS) binding protein with gram-negative bactericidal activity
      in the leukocytes. In this study, we characterized the previously unknown effects
      of BPI in the eye and the molecular mechanisms involved in its action. BPI mRNA
      was detected in bovine retina; retinal pigment epithelium; and primary cultures
      of bovine retinal pigment epithelial cells (RPE), pericytes (RPC), and
      endothelial cells (REC); while BPI protein was measured in human vitreous and
      plasma. BPI, but not control protein thaumatin, activated extracellular regulated
      kinase (ERK) and AKT, and increased DNA synthesis in RPE and RPC but not in REC.
      A human recombinant 21 kDa modified amino-terminal fragment of BPI (rBPI21)
      reduced H2O2-induced apoptosis in RPE and inhibited vascular endothelial growth
      factor (VEGF)-stimulated ERK phosphorylation in REC when preincubated with VEGF.
      Intraperitoneal (i.p.)-injected rBPI21 reduced ischemia-induced retinal
      neovascularization and diabetes-induced retinal permeability. Since BPI has
      unusual dual properties of promoting RPC and RPE growth while suppressing VEGF
      induced REC growth and vascular permeability, the mechanistic understanding of
      BPI's action may provide novel therapeutic opportunities for diabetic retinopathy
      and age-related macular degeneration.

PMID- 17012260
TI  - Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in
      vitro differentiation potential toward microglia.
AB  - Recent evidence indicates that microglial cells may not derive from blood
      circulating mature monocytes as they express features of myeloid progenitors.
      Here, we observed that a subpopulation of microglial cells expressed CD34 and
      B220 antigens during brain development. We thus hypothesized that microglia, or a
      subset of microglial cells, originate from blood circulating CD34+/B220+ myeloid
      progenitors, which could target the brain under developmental or
      neuroinflammatory conditions. Using experimental allergic encephalomyelitis (EAE)
      as a model of chronic neuroinflammation, we found that a discrete population of
      CD34+/B220+ cells expands in both blood and brain of diseased animals. In EAE
      mice, intravenous transfer experiments showed that macrophage-colony stimulating
      factor (M-CSF) -expanded CD34+ myeloid progenitors target the inflamed central
      nervous system (CNS) while keeping their immature phenotype. Based on these
      results, we then assessed whether CD34+/B220+ cells display in vitro
      differentiation potential toward microglia. For this purpose, CD34+/B220+ cells
      were sorted from M-CSF-stimulated bone marrow (BM) cultures and exposed to a
      glial cell conditioned medium. Under these experimental conditions, CD34+/B220+
      cells were able to differentiate into microglial-like cells showing the
      morphological and phenotypic features of native microglia. Overall, our data
      suggest that under developmental or neuroinflammatory conditions, a subpopulation
      of microglial cells derive from CNS-invading CD34+/B220+ myeloid progenitors.

PMID- 17012261
TI  - Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK
      2/STAT-3 pathways downstream of alpha7 nicotinic receptor in oral keratinocytes.
AB  - The use of tobacco products is associated with an increased incidence of
      periodontal disease, poor response to periodontal therapy, and a high risk for
      developing head and neck cancer. Nicotine and tobacco-derived nitrosamines have
      been shown to exhibit their pathobiologic effects due in part to activation of
      the nicotinic acetylcholine (ACh) receptors (nAChRs), mainly alpha7 nAChR,
      expressed by oral keratinocytes (KCs). This study was designed to gain
      mechanistic insight into alpha7-mediated morbidity of tobacco products in the
      oral cavity. We investigated the signaling pathways downstream of alpha7 nAChR in
      monolayers of oral KCs exposed for 24 h to aged and diluted sidestream cigarette
      smoke (ADSS) or an equivalent concentration of pure nicotine. By both real-time
      polymerase chain reaction (PCR) and In-cell Western, the KCs stimulated with ADSS
      or nicotine showed multifold increases of STAT-3. These effects could be
      completely blocked or significantly (P<0.05) diminished if the cells were
      pretreated with the alpha7 antagonist alpha-bungarotoxin (alphaBTX) or
      transfected with anti-alpha7 small interfering RNA (siRNA-alpha7). The use of
      pathway inhibitors revealed that signaling through the Ras/Raf-1/MEK1/ERK steps
      mediated alpha7-dependent up-regulation of STAT-3. Targeted mutation of the
      alpha7 gene prevented ERK1/2 activation by nicotine. Using the gel mobility shift
      assay, we demonstrated that an increased protein binding activity of STAT-3
      caused by ADSS or pure nicotine was mediated by janus-activated kinase (JAK)-2.
      Activation of JAK-2/STAT-3 pathway could be prevented by alphaBTX or siRNA
      alpha7. Thus, nuclear transactivation of STAT-3 in KCs exposed to tobacco
      products is mediated via intracellular signaling downstream from alpha7, which
      proceeds via two complementary pathways. The Ras/Raf-1/MEK1/ERK cascade
      culminates in up-regulated expression of the gene encoding STAT-3, whereas
      recruitment and activation of tyrosine kinase JAK-2 phosphorylates it.
      Elucidation of this novel mechanism of nicotine-dependent nuclear transactivation
      of STAT-3 identifies oral alpha7 nAChR as a promising molecular target to
      prevent, reverse, or retard tobacco-related periodontal disease and progression
      of head and neck cancer by receptor inhibitors.

PMID- 17012262
TI  - Obscurin modulates the assembly and organization of sarcomeres and the
      sarcoplasmic reticulum.
AB  - Obscurin (approximately 800 kDa) in striated muscle closely surrounds sarcomeres
      at the level of the M-band and Z-disk where, we hypothesize, it participates in
      the assembly of the contractile apparatus and membrane systems required for Ca2+
      homeostasis. In this study, we used small inhibitory RNA (siRNA) technology to
      reduce the levels of obscurin in primary cultures of skeletal myotubes to study
      its role in myofibrillogenesis and the organization of the sarcoplasmic reticulum
      (SR). siRNA-treated myotubes showed a specific and dramatic reduction in the
      approximately 800 kDa form of obscurin by reverse transcription-polymerase chain
      reaction, immunoblotting, and immunofluorescence. M-bands and A-bands, but not Z
      disks or I-bands, were disrupted when the synthesis of obscurin was inhibited.
      Small ankyrin 1, an integral protein of the network SR that binds to obscurin,
      also failed to align around developing sarcomeres in treated myotubes. Myosin and
      myomesin levels were significantly reduced in treated myotubes but alpha-actinin
      was not, suggesting that down-regulation of obscurin destabilizes proteins of the
      M-band and A-band but not of the Z-disk. Our findings suggest that obscurin is
      required for the assembly of the M-band and A-band and for the regular alignment
      of the network SR around the contractile apparatus.

PMID- 17012263
TI  - The novel vitamin D analog ZK191784 as an intestine-specific vitamin D
      antagonist.
AB  - Vitamin D [1,25(OH)2D3] plays a crucial role in Ca2+ homeostasis by stimulating
      Ca2+ (re)absorption and bone turnover. The 1,25(OH)2D3 analog ZK191784 was
      recently developed to dissociate the therapeutic immunomodulatory activity from
      the hypercalcemic side effects of 1,25(OH)2D3 and contains a structurally
      modified side chain characterized by a 22,23-double bond, 24R-hydroxy group, 25
      cyclopropyl ring, and 5-butyloxazole unit. We investigated the effect of ZK191784
      on Ca2+ homeostasis and the regulation of Ca2+ transport proteins in wild-type
      (WT) mice and mice lacking the renal epithelial Ca2+ channel TRPV5 (TRPV5-/-).
      The latter display hypercalciuria, hypervitaminosis D, increased intestinal
      expression of the epithelial Ca2+ channel TRPV6, the Ca2+-binding protein
      calbindin-D(9K), and intestinal Ca2+ hyperabsorption. ZK191784 normalized the
      Ca2+ hyperabsorption and the expression of intestinal Ca2+ transport proteins in
      TRPV5-/- mice. Furthermore, the compound decreased intestinal Ca2+ absorption in
      WT mice and reduced 1,25(OH)2D3-dependent 45Ca2+ uptake by Caco-2 cells,
      substantiating a 1,25(OH)2D3-antagonistic action of ZK191784 in the intestine.
      ZK191784 increased renal TRPV5 and calbindin-D(28K) expression and decreased
      urine Ca2+ excretion in WT mice. Both 1,25(OH)2D3 and ZK191784 enhanced
      transcellular Ca2+ transport in primary cultures of rabbit connecting tubules and
      cortical collecting ducts, indicating a 1,25(OH)2D3-agonistic effect in kidney.
      ZK191784 enhanced bone TRPV6 mRNA levels and 1,25(OH)2D3 as well as ZK191784
      stimulated secretion of the bone formation marker osteocalcin in rat osteosarcoma
      cells, albeit to a different extent. In conclusion, ZK191784 is a synthetic
      1,25(OH)2D3 ligand displaying a unique tissue-specific profile when administered
      in vivo. Because ZK191784 acts as an intestine-specific 1,25(OH)2D3 antagonist,
      this compound will be associated with less hypercalcemic side effects compared
      with the 1,25(OH)2D3 analogs currently used in clinical practice.

PMID- 17012264
TI  - No association between polymorphism in PEMT (V175M) and hepatic triglyceride
      content in the Dallas Heart Study.

PMID- 17012266
TI  - Mobilisation with movement and exercise, corticosteroid injection, or wait and
      see for tennis elbow: randomised trial.
AB  - OBJECTIVE: To investigate the efficacy of physiotherapy compared with a wait and
      see approach or corticosteroid injections over 52 weeks in tennis elbow. DESIGN:
      Single blind randomised controlled trial. SETTING: Community setting, Brisbane,
      Australia. PARTICIPANTS: 198 participants aged 18 to 65 years with a clinical
      diagnosis of tennis elbow of a minimum six weeks' duration, who had not received
      any other active treatment by a health practitioner in the previous six months.
      INTERVENTIONS: Eight sessions of physiotherapy; corticosteroid injections; or
      wait and see. MAIN OUTCOME MEASURES: Global improvement, grip force, and
      assessor's rating of severity measured at baseline, six weeks, and 52 weeks.
      RESULTS: Corticosteroid injection showed significantly better effects at six
      weeks but with high recurrence rates thereafter (47/65 of successes subsequently
      regressed) and significantly poorer outcomes in the long term compared with
      physiotherapy. Physiotherapy was superior to wait and see in the short term; no
      difference was seen at 52 weeks, when most participants in both groups reported a
      successful outcome. Participants who had physiotherapy sought less additional
      treatment, such as non-steroidal anti-inflammatory drugs, than did participants
      who had wait and see or injections. CONCLUSION: Physiotherapy combining elbow
      manipulation and exercise has a superior benefit to wait and see in the first six
      weeks and to corticosteroid injections after six weeks, providing a reasonable
      alternative to injections in the mid to long term. The significant short term
      benefits of corticosteroid injection are paradoxically reversed after six weeks,
      with high recurrence rates, implying that this treatment should be used with
      caution in the management of tennis elbow.

PMID- 17012267
TI  - Comparison of academic performance of twins and singletons in adolescence: follow
      up study.
AB  - OBJECTIVES: To determine whether twins in recent cohorts show similar academic
      performance in adolescence to singletons and to test the effect of birth weight
      on academic performance in twins and singletons. DESIGN: Follow-up study.
      SETTING: Denmark. PARTICIPANTS: All twins (n=3411) and a 5% random sample of
      singletons (n=7796) born in Denmark during 1986-8. MAIN OUTCOME MEASURES: Test
      scores in ninth grade (age 15 or 16), birth weight, gestational age at birth,
      parents' age, and parents' education. RESULTS: Ninth grade test scores were
      normally distributed, with almost identical mean and standard deviations for
      twins and singletons (8.02 v 8.02 and 1.05 v 1.06) despite the twins weighing on
      average 908 g (95% confidence interval 886 to 930 g) less than the singletons at
      birth. Controlling for birth weight, gestational age at birth, age at test, and
      parents' age and education confirmed the similarity of test scores for twins and
      singletons (difference 0.04, 95% confidence interval -0.03 to 0.10). A
      significant, positive association between test score and birth weight was
      observed in both twins and singletons, but the size of the effect was small: 0.06
      0.12 standard deviations for every kilogram increase in birth weight.
      CONCLUSIONS: Although older cohorts of twins have been found to have lower mean
      IQ scores than singletons, twins in recent Danish cohorts show similar academic
      performance in adolescence to that of singletons. Birth weight has a minimal
      effect on academic performance in recent cohorts; for twins this effect is best
      judged relative to what is a normal birth weight for twins and not for
      singletons.

PMID- 17012268
TI  - Mutation analyses of Uroplakin II in children with renal tract malformations.
AB  - BACKGROUND: Uroplakin (UP) proteins cover urothelial apical surfaces. Mice
      lacking UPIIIa have elevated urothelial permeability and congenital renal tract
      anomalies, and UPIIIa mutations have been reported in children with kidney and
      ureter malformations. Mice with null mutation of another UP family member, UPII,
      are often born with congenital hydronephrosis. We hypothesized that UPII
      mutations may be present in humans with renal tract malformations. METHODS:
      Mutations were sought, using direct sequencing of the five UPII exons, in 42
      children with diverse renal tract anomalies. RESULTS: No UPII abnormalities were
      detected in 41 patients, whereas one index case had a heterozygous frameshift
      change which, if expressed, would generate a truncated protein. This Caucasian
      child presented with vesicoureteric reflux (VUR), bilateral nephropathy and renal
      failure. The genetic change was also found in the index case's mother who had
      normal renal ultrasonography, but it was absent in 150 healthy Caucasian control
      individuals (96 assessed by direct sequencing and another 54 assessed by
      restriction digests). UPII was immunolocalized in urothelium of the normal human
      embryonic renal pelvis in a pattern similar to UPIIIa. CONCLUSION: This study
      offers no definitive support for UPII mutations causing human renal tract
      malformations. In rare patients, UPII variants might be implicated in
      pathogenesis when acting in conjunction with other yet-to-be-defined, genetic or
      environmental modifying factors.

PMID- 17012269
TI  - Non-random, individual-specific methylation profiles are present at the sixth
      CTCF binding site in the human H19/IGF2 imprinting control region.
AB  - Expression of imprinted genes is classically associated with differential
      methylation of specific CpG-rich DNA regions (DMRs). The H19/IGF2 locus is
      considered a paradigm for epigenetic regulation. In mice, as in humans, the
      essential H19 DMR--target of the CTCF insulator--is located between the two
      genes. Here, we performed a pyrosequencing-based quantitative analysis of its CpG
      methylation in normal human tissues. The quantitative analysis of the methylation
      level in the H19 DMR revealed three unexpected discrete, individual-specific
      methylation states. This epigenetic polymorphism was confined to the sixth CTCF
      binding site while a unique median-methylated profile was found at the third CTCF
      binding site as well as in the H19 promoter. Monoallelic expression of H19 and
      IGF2 was maintained independently of the methylation status at the sixth CTCF
      binding site and the IGF2 DMR2 displayed a median-methylated profile in all
      individuals and tissues analyzed. Interestingly, the methylation profile was
      genetically transmitted. Transgenerational inheritance of the H19 methylation
      profile was compatible with a simple model involving one gene with three alleles.
      The existence of three individual-specific epigenotypes in the H19 DMR in a non
      pathological situation means it is important to reconsider the diagnostic value
      and functional importance of the sixth CTCF binding site.

PMID- 17012270
TI  - A novel endonuclease IV post-PCR genotyping system.
AB  - Here we describe a novel endonuclease IV (Endo IV) based assay utilizing a
      substrate that mimics the abasic lesions that normally occur in double-stranded
      DNA. The three component substrate is characterized by single-stranded DNA
      target, an oligonucleotide probe, separated from a helper oligonucleotide by a
      one base gap. The oligonucleotide probe contains a non-fluorescent quencher at
      the 5' end and fluorophore attached to the 3' end through a special rigid linker.
      Fluorescence of the oligonucleotide probe is efficiently quenched by the
      interaction of terminal dye and quencher when not hybridized. Upon hybridization
      of the oligonucleotide probe and helper probe to their complementary target, the
      phosphodiester linkage between the rigid linker and the 3' end of the probe is
      efficiently cleaved, generating a fluorescent signal. In this study, the use of
      the Endo IV assay as a post-PCR amplification detection system is demonstrated.
      High sensitivity and specificity are illustrated using single nucleotide
      polymorphism detection.

PMID- 17012271
TI  - Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified
      bases in mRNA recognition.
AB  - Accuracy in translation of the genetic code into proteins depends upon correct
      tRNA-mRNA recognition in the context of the ribosome. In human tRNA(Lys,3)UUU
      three modified bases are present in the anticodon stem-loop--2-methylthio-N6
      threonylcarbamoyladenosine at position 37 (ms2t6A37), 5-methoxycarbonylmethyl-2
      thiouridine at position 34 (mcm5s2U34) and pseudouridine (psi) at position 39-
      two of which, ms2t6A37 and mcm5s2U34, are required to achieve wild-type binding
      activity of wild-type human tRNA(Lys,3)UUU [C. Yarian, M. Marszalek, E. Sochacka,
      A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry,
      39, 13390-13395]. Molecular dynamics simulations of nine tRNA anticodon stem
      loops with different combinations of nonstandard bases were performed. The wild
      type simulation exhibited a canonical anticodon stair-stepped conformation. The
      ms2t6 modification at position 37 is required for maintenance of this structure
      and reduces solvent accessibility of U36. Ms2t6A37 generally hydrogen bonds
      across the loop and may prevent U36 from rotating into solution. A water molecule
      does coordinate to psi39 most of the simulation time but weakly, as most of the
      residence lifetimes are <40 ps.

PMID- 17012272
TI  - Robust analysis of 5'-transcript ends (5'-RATE): a novel technique for
      transcriptome analysis and genome annotation.
AB  - Complicated cloning procedures and the high cost of sequencing have inhibited the
      wide application of serial analysis of gene expression and massively parallel
      signature sequencing for genome-wide transcriptome profiling of complex genomes.
      Here we describe a new method called robust analysis of 5'-transcript ends (5'
      RATE) for rapid and cost-effective isolation of long 5' transcript ends
      (approximately 80 bp). It consists of three major steps including 5'-oligocapping
      of mRNA, NlaIII tag and ditag generation, and pyrosequencing of NlaIII tags.
      Complicated steps, such as purification and cloning of concatemers, colony
      picking and plasmid DNA purification, are eliminated and the conventional Sanger
      sequencing method is replaced with the newly developed pyrosequencing method.
      Sequence analysis of a maize 5'-RATE library revealed complex alternative
      transcription start sites and a 5' poly(A) tail in maize transcripts. Our results
      demonstrate that 5'-RATE is a simple, fast and cost-effective method for
      transcriptome analysis and genome annotation of complex genomes.

PMID- 17012273
TI  - SIR2 modifies histone H4-K16 acetylation and affects superhelicity in the ARS
      region of plasmid chromatin in Saccharomyces cerevisiae.
AB  - The null mutation of the SIR2 gene in Saccharomyces cerevisiae has been
      associated with a series of different phenotypes including loss of
      transcriptional silencing, genome instability and replicative aging. Thus, the
      SIR2 gene product is an important constituent of the yeast cell. SIR2 orthologues
      and paralogues have been discovered in organisms ranging from bacteria to man,
      underscoring the pivotal role of this protein. Here we report that a plasmid
      introduced into sir2Delta cells accumulates more negative supercoils compared to
      the same plasmid introduced into wild-type (WT) cells. This effect appears to be
      directly related to SIR2 expression as shown by the reduction of negative
      supercoiling when SIR2 is overexpressed, and does not depend on the number or
      positioning of nucleosomes on plasmids. Our results indicate that this new
      phenotype is due to the lack of Sir2p histone deacetylase activity in the
      sir2Delta strain, because only the H4-K16 residue of the histone octamer
      undergoes an alteration of its acetylation state. A model proposing interference
      with the replication machinery is discussed.

PMID- 17012274
TI  - 3D reconstruction and comparison of shapes of DNA minicircles observed by cryo
      electron microscopy.
AB  - We use cryo-electron microscopy to compare 3D shapes of 158 bp long DNA
      minicircles that differ only in the sequence within an 18 bp block containing
      either a TATA box or a catabolite activator protein binding site. We present a
      sorting algorithm that correlates the reconstructed shapes and groups them into
      distinct categories. We conclude that the presence of the TATA box sequence,
      which is believed to be easily bent, does not significantly affect the observed
      shapes.

PMID- 17012275
TI  - Collision events between RNA polymerases in convergent transcription studied by
      atomic force microscopy.
AB  - Atomic force microscopy (AFM) has been used to image, at single molecule
      resolution, transcription events by Escherichia coli RNA polymerase (RNAP) on a
      linear DNA template with two convergently aligned lambda(pr) promoters. For the
      first time experimentally, the outcome of collision events during convergent
      transcription by two identical RNAP has been studied. Measurement of the
      positions of the RNAP on the DNA, allows distinction of open promoter complexes
      (OPCs) and elongating complexes (EC) and collided complexes (CC). This
      discontinuous time-course enables subsequent analysis of collision events where
      both RNAP remain bound on the DNA. After collision, the elongating RNAP has
      caused the other (usually stalled) RNAP to back-track along the template. The
      final positions of the two RNAP indicate that these are collisions between an EC
      and a stalled EC (SEC) or OPC (previously referred to as sitting-ducks).
      Interestingly, the distances between the two RNAP show that they are not always
      at closest approach after 'collision' has caused their arrest.

PMID- 17012277
TI  - In vivo DNase I sensitivity of the Streptomyces coelicolor chromosome correlates
      with gene expression: implications for bacterial chromosome structure.
AB  - For a bacterium, Streptomyces coelicolor A3(2) contains a relatively large genome
      (8.7 Mb) with a complex and adaptive pattern of gene regulation. We discovered a
      correlation between the physical structure of the S.coelicolor genome and the
      transcriptional activity of the genes therein. Twelve genes were surveyed
      throughout 72 h of growth for both in vivo sensitivity to DNase I digestion and
      levels of transcription. DNase I-sensitivity correlated positively with
      transcript levels, implying that it was predictive of gene expression, and
      indicating increased accessibility of transcribed DNA. The genome was
      fractionated based on the sensitivity to DNase I digestion, with the low
      molecular weight (frequently cut) fraction highly enriched for actively
      transcribed sequences when compared to the infrequently cut fraction, which was
      representative of the entire genome. This approach will allow comparison of
      nucleoid proteins, and any modifications thereof, associated with
      transcriptionally active and inactive regions of the bacterial genome.

PMID- 17012276
TI  - Quadruplex DNA: sequence, topology and structure.
AB  - G-quadruplexes are higher-order DNA and RNA structures formed from G-rich
      sequences that are built around tetrads of hydrogen-bonded guanine bases.
      Potential quadruplex sequences have been identified in G-rich eukaryotic
      telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease
      hypersensitive promoter regions. The natural role and biological validation of
      these structures is starting to be explored, and there is particular interest in
      them as targets for therapeutic intervention. This survey focuses on the folding
      and structural features on quadruplexes formed from telomeric and non-telomeric
      DNA sequences, and examines fundamental aspects of topology and the emerging
      relationships with sequence. Emphasis is placed on information from the high
      resolution methods of X-ray crystallography and NMR, and their scope and current
      limitations are discussed. Such information, together with biological insights,
      will be important for the discovery of drugs targeting quadruplexes from
      particular genes.

PMID- 17012278
TI  - Systematic characterization of 2'-deoxynucleoside- 5'-triphosphate analogs as
      substrates for DNA polymerases by polymerase chain reaction and kinetic studies
      on enzymatic production of modified DNA.
AB  - We synthesized C5-modified analogs of 2'-deoxyuridine triphosphate and 2'
      deoxycytidine triphosphate and investigated them as substrates for PCRs using
      Taq, Tth, Vent(exo-), KOD Dash and KOD(exo-) polymerases and pUC 18 plasmid DNA
      as a template. These assays were performed on two different amplifying regions of
      pUC18 with different T/C contents that are expected to have relatively high
      barriers for incorporation of either modified dU or dC. On the basis of 260
      different assays (26 modified triphosphates x 5 DNA polymerases x 2 amplifying
      regions), it appears that generation of the full-length PCR product depends not
      only on the chemical structures of the substitution and the nature of the
      polymerase but also on whether the substitution is on dU or dC. Furthermore, the
      template sequence greatly affected generation of the PCR product, depending on
      the combination of the DNA polymerase and modified triphosphate. By examining
      primer extension reactions using primers and templates containing C5-modified
      dUs, we found that a modified dU at the 3' end of the elongation strand greatly
      affects the catalytic efficiency of DNA polymerases, whereas a modified dU
      opposite the elongation site on the template strand has less of an influence on
      the catalytic efficiency.

PMID- 17012279
TI  - In vitro evolution of single-chain antibodies using mRNA display.
AB  - Here we describe the application of the in vitro virus mRNA display method, which
      involves covalent linkage of an in vitro-synthesized antibody (phenotype) to its
      encoding mRNA (genotype) through puromycin, for in vitro evolution of single
      chain Fv (scFv) antibody fragments. To establish the validity of this approach to
      directed antibody evolution, we used random mutagenesis by error-prone DNA
      shuffling and off-rate selection to improve the affinity of an anti-fluorescein
      scFv as a model system. After four rounds of selection of the library of mRNA
      displayed scFv mutants, we obtained six different sequences encoding affinity
      matured mutants with five consensus mutations. Kinetic analysis of the mutant
      scFvs revealed that the off-rates have been decreased by more than one order of
      magnitude and the dissociation constants were improved approximately 30-fold. The
      antigen-specificity was not improved by affinity maturation, but remained similar
      to that of the wild type. Although the five consensus mutations of the high
      affinity mutants were scattered over the scFv sequence, analysis by site-directed
      mutagenesis demonstrated that the critical mutations for improving affinity were
      the two that lay within the complementarity determining regions (CDRs). Thus,
      mRNA display is expected to be useful for rapid artificial evolution of high
      affinity diagnostic and therapeutic antibodies by optimizing their CDRs.

PMID- 17012280
TI  - Double-strand breaks in the myotonic dystrophy type 1 and the fragile X syndrome
      triplet repeat sequences induce different types of mutations in DNA flanking
      sequences in Escherichia coli.
AB  - The putative role of double-strand breaks (DSBs) created in vitro by restriction
      enzyme cleavage in or near CGG*CCG or CTG*CAG repeat tracts on their genetic
      instabilities, both within the repeats and in their flanking sequences, was
      investigated in an Escherichia coli plasmid system. DSBs at TRS junctions with
      the vector generated a large number of mutagenic events in flanking sequences
      whereas DSBs within the repeats elicited no similar products. A substantial
      enhancement in the number of mutants was caused by transcription of the repeats
      and by the absence of recombination functions (recA-, recBC-). Surprisingly, DNA
      sequence analyses on mutant clones revealed the presence of only single deletions
      of 0.4-1.6 kb including the TRS and the flanking sequence from plasmids
      originally containing (CGG*CCG)43 but single, double and multiple deletions as
      well as insertions were found for plasmids originally containing (CTG*CAG)n
      (where n = 43 or 70). Non-B DNA structures (slipped structures with loops,
      cruciforms, triplexes and tetraplexes) as well as microhomologies are postulated
      to participate in the recombination and/or repair processes.

PMID- 17012281
TI  - A nucleosome assembly protein-like polypeptide binds to chloroplast group II
      intron RNA in Chlamydomonas reinhardtii.
AB  - In the unicellular green alga Chlamydomonas reinhardtii, the chloroplast-encoded
      tscA RNA is part of a tripartite group IIB intron, which is involved in trans
      splicing of precursor mRNAs. We have used the yeast three-hybrid system to
      identify chloroplast group II intron RNA-binding proteins, capable of interacting
      with the tscA RNA. Of 14 candidate cDNAs, 13 encode identical polypeptides with
      significant homology to members of the nuclear nucleosome assembly protein (NAP)
      family. The RNA-binding property of the identified polypeptide was demonstrated
      by electrophoretic mobility shift assays using different domains of the
      tripartite group II intron as well as further chloroplast transcripts. Because of
      its binding to chloroplast RNA it was designated as NAP-like (cNAPL). In silico
      analysis revealed that the derived polypeptide carries a 46 amino acid
      chloroplast leader peptide, in contrast to nuclear NAPs. The chloroplast
      localization of cNAPL was demonstrated by laser scanning confocal fluorescence
      microscopy using different chimeric cGFP fusion proteins. Phylogenetic analysis
      shows that no homologues of cNAPL and its related nuclear counterparts are
      present in prokaryotic genomes. These data indicate that the chloroplast protein
      described here is a novel member of the NAP family and most probably has not been
      acquired from a prokaryotic endosymbiont.

PMID- 17012282
TI  - The Methanothermobacter thermautotrophicus ExoIII homologue Mth212 is a DNA
      uridine endonuclease.
AB  - The genome of Methanothermobacter thermautotrophicus, as a hitherto unique case,
      is apparently devoid of genes coding for general uracil DNA glycosylases, the
      universal mediators of base excision repair following hydrolytic deamination of
      DNA cytosine residues. We have now identified protein Mth212, a member of the
      ExoIII family of nucleases, as a possible initiator of DNA uracil repair in this
      organism. This enzyme, in addition to bearing all the enzymological hallmarks of
      an ExoIII homologue, is a DNA uridine endonuclease (U-endo) that nicks double
      stranded DNA at the 5'-side of a 2'-d-uridine residue, irrespective of the nature
      of the opposing nucleotide. This type of activity has not been described before;
      it is absent from the ExoIII homologues of Escherichia coli, Homo sapiens and
      Methanosarcina mazei, all of which are equipped with uracil DNA repair
      glycosylases. The U-endo activity of Mth212 is served by the same catalytic
      center as its AP-endo activity.

PMID- 17012284
TI  - Automated identification of multiple micro-organisms from resequencing DNA
      microarrays.
AB  - There is an increasing recognition that detailed nucleic acid sequence
      information will be useful and even required in the diagnosis, treatment and
      surveillance of many significant pathogens. Because generating detailed
      information about pathogens leads to significantly larger amounts of data, it is
      necessary to develop automated analysis methods to reduce analysis time and to
      standardize identification criteria. This is especially important for multiple
      pathogen assays designed to reduce assay time and costs. In this paper, we
      present a successful algorithm for detecting pathogens and reporting the maximum
      level of detail possible using multi-pathogen resequencing microarrays. The
      algorithm filters the sequence of base calls from the microarray and finds
      entries in genetic databases that most closely match. Taxonomic databases are
      then used to relate these entries to each other so that the microorganism can be
      identified. Although developed using a resequencing microarray, the approach is
      applicable to any assay method that produces base call sequence information. The
      success and continued development of this approach means that a non-expert can
      now perform unassisted analysis of the results obtained from partial sequence
      data.

PMID- 17012283
TI  - Post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in
      Trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage
      specific regulatory elements.
AB  - Trypanosomes represent an excellent model for the post-transcriptional regulation
      of gene expression because their genome is organized into polycistronic
      transcription units. However, few signals governing developmental stage-specific
      expression have been identified, with there being no compelling evidence for
      widespread conservation of regulatory motifs. As a tool to search for common
      regulatory sequences we have used the nuclear-encoded components of the
      cytochrome oxidase (COX) complex of the trypanosome respiratory chain. Components
      of this complex represent a form of post-transcriptional operon because
      trypanosome mitochondrial activity is unusual in being developmentally
      programmed. By genome analysis we identified the genes for seven components of
      the COX complex. Each mRNA exhibits bloodstream stage-specific instability, which
      is not mediated by the RNA silencing pathway but which is alleviated by
      cycloheximide. Reporter assays have identified regulatory regions within the 3'
      untranslated regions of three COX mRNAs operating principally at the
      translational level, but also via mRNA stability. Interrogation of the mapped
      regions via oligonucleotide frequency scoring provides evidence for genome-wide
      conservation of regulatory sequences among a large cohort of procyclic-enriched
      transcripts. Analysis of the co-regulated subunits of a stage-specific enzyme is
      therefore a novel approach to uncover cryptic regulatory sequences controlling
      gene expression at the post-transcriptional level.

PMID- 17012285
TI  - An evolutionary 'intermediate state' of mitochondrial translation systems found
      in Trichinella species of parasitic nematodes: co-evolution of tRNA and EF-Tu.
AB  - EF-Tu delivers aminoacyl-tRNAs to ribosomes in the translation system. However,
      unusual truncations found in some animal mitochondrial tRNAs seem to prevent
      recognition by a canonical EF-Tu. We showed previously that the chromadorean
      nematode has two distinct EF-Tus, one of which (EF-Tu1) binds only to T-armless
      aminoacyl-tRNAs and the other (EF-Tu2) binds to D-armless Ser-tRNAs. Neither of
      the EF-Tus can bind to canonical cloverleaf tRNAs. In this study, by analyzing
      the translation system of enoplean nematode Trichinella species, we address how
      EF-Tus and tRNAs have evolved from the canonical structures toward those of the
      chromadorean translation system. Trichinella mitochondria possess three types of
      tRNAs: cloverleaf tRNAs, which do not exist in chromadorean nematode
      mitochondria; T-armless tRNAs; and D-armless tRNAs. We found two mitochondrial EF
      Tu species, EF-Tu1 and EF-Tu2, in Trichinella britovi. T.britovi EF-Tu2 could
      bind to only D-armless Ser-tRNA, as Caenorhabditis elegans EF-Tu2 does. In
      contrast to the case of C.elegans EF-Tu1, however, T.britovi EF-Tu1 bound to all
      three types of tRNA present in Trichinella mitochondria. These results suggest
      that Trichinella mitochondrial translation system, and particularly the tRNA
      binding specificity of EF-Tu1, could be an intermediate state between the
      canonical system and the chromadorean nematode mitochondrial system.

PMID- 17012286
TI  - Hypothesis: bacterial clamp loader ATPase activation through DNA-dependent
      repositioning of the catalytic base and of a trans-acting catalytic threonine.
AB  - The prokaryotic DNA polymerase III clamp loader complex loads the beta clamp onto
      DNA to link the replication complex to DNA during processive synthesis and
      unloads it again once synthesis is complete. This minimal complex consists of one
      delta, one delta' and three gamma subunits, all of which possess an AAA+ module-
      though only the gamma subunit exhibits ATPase activity. Here clues to underlying
      clamp loader mechanisms are obtained through Bayesian inference of various
      categories of selective constraints imposed on the gamma and delta' subunits. It
      is proposed that a conserved histidine is ionized via electron transfer involving
      structurally adjacent residues within the sensor 1 region of gamma's AAA+ module.
      The resultant positive charge on this histidine inhibits ATPase activity by
      drawing the negatively charged catalytic base away from the active site. It is
      also proposed that this arrangement is disrupted upon interaction of DNA with
      basic residues in gamma implicated previously in DNA binding, regarding which a
      lysine that is near the sensor 1 region and that is highly conserved both in
      bacterial and in eukaryotic clamp loader ATPases appears to play a critical role.
      gamma ATPases also appear to utilize a trans-acting threonine that is donated by
      helix 6 of an adjacent gamma or delta' subunit and that assists in the activation
      of a water molecule for nucleophilic attack on the gamma phosphorous atom of ATP.
      As eukaryotic and archaeal clamp loaders lack most of these key residues, it
      appears that eubacteria utilize a fundamentally different mechanism for clamp
      loader activation than do these other organisms.

PMID- 17012287
TI  - Structural and functional analysis of the MutS C-terminal tetramerization domain.
AB  - The Escherichia coli DNA mismatch repair (MMR) protein MutS is essential for the
      correction of DNA replication errors. In vitro, MutS exists in a dimer/tetramer
      equilibrium that is converted into a monomer/dimer equilibrium upon deletion of
      the C-terminal 53 amino acids. In vivo and in vitro data have shown that this C
      terminal domain (CTD, residues 801-853) is critical for tetramerization and the
      function of MutS in MMR and anti-recombination. We report the expression,
      purification and analysis of the E.coli MutS-CTD. Secondary structure prediction
      and circular dichroism suggest that the CTD is folded, with an alpha-helical
      content of 30%. Based on sedimentation equilibrium and velocity analyses, MutS
      CTD forms a tetramer of asymmetric shape. A single point mutation (D835R)
      abolishes tetramerization but not dimerization of both MutS-CTD and full-length
      MutS. Interestingly, the in vivo and in vitro MMR activity of MutS(CF/D835R) is
      diminished to a similar extent as a truncated MutS variant (MutS800, residues 1
      800), which lacks the CTD. Moreover, the dimer-forming MutS(CF/D835R) has
      comparable DNA binding affinity with the tetramer-forming MutS, but is impaired
      in mismatch-dependent activation of MutH. Our data support the hypothesis that
      tetramerization of MutS is important but not essential for MutS function in MMR.

PMID- 17012288
TI  - Regulating a circadian clock's period, phase and amplitude by phosphorylation:
      insights from Drosophila.
AB  - Much progress has been made in understanding the molecular underpinnings
      governing circadian ( approximately 24 h) rhythms. Despite the increased
      complexity in metazoans whereby inter-cellular networks form the basis for
      driving overt rhythms, such as wake-sleep cycles in animals, single isolated
      cells can exhibit all the formal properties of a circadian pacemaker. How do
      these cell-autonomous rhythm generators operate? Breakthrough studies in
      Drosophila melanogaster led to the realization that the molecular logic
      underlying circadian clocks are highly shared. Most notably, interconnected
      transcriptional-translational feedback loops produce coordinated rhythms in
      "clock" RNAs and proteins that are required for the daily progression of clocks,
      synchronization to local time and transducing temporal signals to downstream
      effector pathways. More recent findings indicate prominent roles for reversible
      phosphorylation of clock proteins in the core oscillatory mechanism. In this
      review we focus on findings in Drosophila to explore the multiple levels that
      reversible phosphorylation plays in clock function. Specific clock proteins in
      this system are subjected to different phosphorylation programs, which affect
      three key properties of a circadian oscillator, its period, amplitude and phase.
      The role of phosphorylation in clocks is of clear relevance to human health
      because mutations that affect the PERIOD (PER) phosphorylation program are
      associated with familial sleep disorders. In addition, the central role of
      phosphorylation in the assembly of a circadian oscillator was dramatically shown
      recently by the ability to reconstitute a circadian
      phosphorylation/dephosphorylation cycle in vitro, suggesting that the dynamics of
      clock protein phosphorylation are at the "heart" of circadian time-keeping.

PMID- 17012289
TI  - Prothymosin alpha interacts with free core histones in the nucleus of dividing
      cells.
AB  - The acidic protein prothymosin alpha (ProTalpha), with a broad presence in
      mammalian cells, has been widely considered to have a role in cell division,
      through an unrevealed mechanism in which histones may be involved in view of
      their ability to interact with ProTalpha in vitro. Results of co
      immunoprecipitation experiments presented here demonstrate that ProTalpha
      interacts in vivo with core histones in proliferating B-lymphocytes (NC-37
      cells). This interaction occurs with histones H3, H2A, H2B and H4 located free in
      the nucleoplasm, whereas no interaction was detected with histone H1, mono
      nucleosome particles or chromatin. Moreover, the core histones form part of a
      nuclear multiprotein complex of about 700 kDa separated by ProTalpha-Sepharose
      affinity, with components including H3 and H4 acetyltranferases, H3
      methyltransferases, hnRNP isotypes A3, A2/B1 and R, ATP-dependent and independent
      DNA helicases II, beta-actin and vimentin, all co-purifying by gel filtration.
      This indicates that the interaction of ProTalpha with core histones in the
      nucleus may be related to the structural modification of histones H3 and H4, and
      hence to chromatin activity, raising the possibility that the other proteins in
      the nuclear complex may play a role in this process.

PMID- 17012291
TI  - Pressure pain thresholds and tender point counts as predictors of new chronic
      widespread pain in somatising subjects.
AB  - BACKGROUND: Tender points are a general measure of distress both in the community
      and in clinic subjects. It has been suggested that multiple tender points should
      be regarded as the early stages of somatisation of distress. Similarly, recent
      evidence suggests that chronic widespread pain (CWP) is one manifestation of the
      somatisation of distress. OBJECTIVE: Given that a high tender point count and CWP
      are clinical hallmarks of the fibromyalgia syndrome, it was hypothesised that in
      somatising subjects, a high tender point count or a low pain threshold would
      predict the development of CWP in the future. METHODS: In this population-based
      prospective study, 245 adults aged 25-65 years, free of CWP, were identified on
      the basis of a detailed questionnaire on pain and a psychosocial questionnaire
      comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of
      the Illness Attitude Scales. These subjects took part in a pain threshold
      examination with a Fischer pressure algometer. Tender point counts were computed
      by including all areas with a pain threshold<4 kg/cm2. Individuals were followed
      up at 15 months, at which time 231 (93% of subjects still living at their
      baseline address) provided data on pain status, using the same instruments.
      RESULTS: At follow-up, 26 (11%) subjects developed new CWP. Although subjects
      with a low baseline pain threshold were not at increased risk of developing
      symptoms, a high tender point count, adjusted for age, sex, baseline pain status
      and other confounding factors, predicted the development of new CWP. CONCLUSION:
      Subjects free of CWP are at an increased risk of its development if they have a
      high tender point count. However, a low-pressure pain threshold does not predict
      the onset of symptoms. Data from this population-based prospective study suggest
      that a low pain threshold in subjects with CWP is likely to be a secondary
      phenomenon as a result of pain or associated distress rather than the antecedent
      of symptoms.

PMID- 17012290
TI  - Role of the MHC2TA gene in autoimmune diseases.
AB  - OBJECTIVES: Expression of major histocompatibility complex (MHC) class II genes
      is almost exclusively regulated by the class II transactivator. A promoter
      polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with
      increased susceptibility to rheumatoid arthritis, multiple sclerosis and
      myocardial infarction in a northern European population. However, no evidence of
      association of this MHC2TA variant with the two autoimmune diseases could be
      subsequently detected in independent cohorts. AIM: To test the aforementioned
      single nucleotide polymorphism and another G-->C change (nt1614 from coding
      sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. METHODS:
      A case-control study was performed with 350 patients with rheumatoid arthritis,
      396 patients with multiple sclerosis, 663 patients with inflammatory bowel
      disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by
      using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer's
      suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were
      inferred with the expectation-maximisation algorithm implemented by the Arlequin
      software. RESULTS: No independent association with these autoimmune diseases was
      found for either polymorphism in the Spanish cohorts tested. However, when
      haplotypes were compared between patients with rheumatoid arthritis and controls,
      a significant difference in their overall frequency distribution was observed,
      evidencing a protective haplotype (-168A/1614C, p = 0.006; odds ratio (OR) 0.7)
      and a risk haplotype (-168G/1614C, p = 0.019; OR 1.6). Patients with multiple
      sclerosis mirrored these results, but no effect on IBD was identified.
      CONCLUSIONS: The MHC2TA gene influences predisposition to rheumatoid arthritis
      and multiple sclerosis, but not to IBD. The -168G allele is not an aetiological
      variant in itself, but a genetic marker of susceptibility/protection haplotypes.

PMID- 17012292
TI  - Individual differences in anatomy predict reading and oral language impairments
      in children.
AB  - Developmental dyslexia (DD) and specific language impairment (SLI) are disorders
      of language that differ in diagnostic criteria and outcome. DD is defined by
      isolated reading deficits. SLI is defined by poor receptive and expressive oral
      language skills. Reading deficits, although prevalent, are not necessary for the
      diagnosis of SLI. An enduring question is whether these two disorders are
      qualitatively different or simply differ quantitatively along a dimension of
      severity. Here we address this problem by examining neuroanatomical correlates of
      reading and language in children with learning disabilities. We asked whether a
      quantitative anatomical risk index derived from previous work could predict
      behavioural profiles in a heterogeneous sample of 14 boys and 8 girls (11-16
      years of age) with reading and language impairments. The results confirmed our
      predictions that (i) children with relatively smaller and symmetrical brain
      structures (negative risk indices) would have the severe comprehension
      impairments typical of SLI; (ii) children with larger, asymmetrical brain
      structures (positive risk indices) would have poor word reading in the presence
      of relatively preserved comprehension, a profile typical of DD; and (iii) the
      best performance would be seen in children with anatomical risk indices near zero
      (normal anatomy). Also, in confirmation of previous work, rapid automatic naming
      was not predicted by the anatomical risk index, but by anatomical measures
      derived from the frontal lobes. These results highlight the key significance of
      comprehension deficits in distinguishing DD from SLI. Reading impaired children
      with and without comprehension deficits appear to occupy neuroanatomical domains
      on the opposite sides of normal.

PMID- 17012293
TI  - CSF phosphorylated tau protein correlates with neocortical neurofibrillary
      pathology in Alzheimer's disease.
AB  - Hyperphosphorylated tau protein (P-tau) in CSF is a core biomarker candidate of
      Alzheimer's disease. Hyperphosphorylation of tau is thought to lead to
      neurofibrillary changes, a neuropathological hallmark of this type of dementia.
      Currently, the question is unresolved whether CSF levels of P-tau reflect
      neurofibrillary changes within the brain of a patient with the illness. Twenty
      six patients were included with intra-vitam CSF as well as post-mortem
      neuropathological data. In the CSF, P-tau phosphorylated at threonine 231 (P
      tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and
      neuritic plaques (NP) were assessed in frontal, temporal, parietal and
      hippocampal cortical areas. In the same cortical regions, load of
      hyperphosphorylated tau protein (HP-tau load) was determined. Concentrations of P
      tau231P were measured in frontal cortex homogenates. We found significant
      correlations between CSF P-tau231P concentrations and scores of NFTs and HP-tau
      load in all neocortical regions studied. The score of NPs was correlated with CSF
      P-tau231P only within the frontal cortex. There was a correlation between P
      tau231P in CSF and brain homogenates. These findings indicate that CSF P-tau231P
      may serve as an in vivo surrogate biomarker of neurofibrillary pathology in
      Alzheimer's disease.

PMID- 17012294
TI  - Enhanced brain activity may precede the diagnosis of Alzheimer's disease by 30
      years.
AB  - Presenilin 1 (PSEN1) mutations cause autosomal dominant familial Alzheimer's
      disease (FAD). PSEN1 mutation carriers undergo the course of cognitive
      deterioration, which is typical for sporadic Alzheimer's disease but disease
      onset is earlier and disease progression is faster. Here, we sought to detect
      signs of FAD in presymptomatic carriers of the PSEN1 mutation (C410Y) by use of a
      neuropsychological examination, functional MRI during learning and memory tasks
      and MRI volumetry. We examined five non-demented members of a FAD family and 21
      non-related controls. Two of the five family members were carrying the mutation;
      one was 20 years old and the other 45 years old. The age of clinical
      manifestation of FAD in the family studied here is approximately 48 years.
      Neuropsychological assessments suggested subtle problems with episodic memory in
      the 20-year-old mutation carrier. The middle-aged mutation carrier fulfilled
      criteria for amnestic mild cognitive impairment. The 20-year-old mutation carrier
      exhibited increased, while the middle-aged mutation carrier exhibited decreased
      brain activity compared to controls within memory-related neural networks during
      episodic learning and retrieval, but not during a working-memory task. The
      increased memory-related brain activity in the young mutation carrier might
      reflect a compensatory effort to overcome preclinical neural dysfunction caused
      by first pathological changes. The activity reductions in the middle-aged
      mutation carrier might reflect gross neural dysfunction in a more advanced stage
      of neuropathology. These data suggest that functional neuroimaging along with
      tasks that challenge specifically those brain areas which are initial targets of
      Alzheimer's disease pathology may reveal activity alterations on a single-subject
      level decades before the clinical manifestation of Alzheimer's disease.

PMID- 17012295
TI  - Alzheimer's centennial legacy: prospects for rational therapeutic intervention
      targeting the Abeta amyloid pathway.
AB  - It is now 100 years since the nosological definition of Alzheimer's disease
      emerged. In the first 80 years, very little progress was made in understanding
      the mechanisms that caused the brain to degenerate in a remarkably specific
      fashion (amyloid accumulation with neurofibrillary changes). Over the past 20
      years, there has been an explosion of knowledge which continues today at an
      exponential rate. The molecular pathways underlying the synaptic dysfunction in
      Alzheimer's disease have delivered many validated therapeutic and diagnostic
      targets. A variety of therapeutic strategies aimed at disease modification are
      now in clinical development.

PMID- 17012296
TI  - Facial onset sensory and motor neuronopathy (FOSMN syndrome): a novel syndrome in
      neurology.
AB  - A 'syringomyelia-like' syndrome has been infrequently reported in neurological
      disorders such as Tangiers disease and lepromatous leprosy. This study reports a
      novel 'syringomyelia-like' syndrome in four adult male patients, which we have
      termed facial onset sensory and motor neuronopathy, or FOSMN syndrome, that
      appears to have a neurodegenerative aetiology. Clinical, neurophysiological and
      pathological data of four patients were reviewed, including the autopsy in one
      patient. Four male patients (mean age at onset 43), initially developed
      paraesthesiae and numbness in a trigeminal nerve distribution, which slowly
      progressed to involve the scalp, neck, upper trunk and upper limbs in sequential
      order. Motor manifestations, including cramps, fasciculations, dysphagia,
      dysarthria, muscle weakness and atrophy developed later in the course of the
      illness. Neurophysiological findings revealed a generalized sensory motor
      neuronopathy of caudally decreasing severity in all four patients. Autopsy in one
      patient disclosed loss of motoneurons in the hypoglossal nucleus and cervical
      anterior horns, along with loss of sensory neurons in the main trigeminal sensory
      nucleus and dorsal root ganglia. FOSMN syndrome appears to be a slowly
      progressive neurodegenerative disorder, whose pathogenesis remains to be
      determined.

PMID- 17012297
TI  - Spiritual health: the next frontier.

PMID- 17012299
TI  - Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.
AB  - AIMS: HMG-CoA reductase inhibitors (statins) reduce cardiovascular mortality and
      morbidity in patients with stable coronary artery disease as well as acute
      coronary syndrome (ACS). It is unclear how rapidly the beneficial effects of
      statins occur in patients with ACS and whether these drug properties are related
      to lipid lowering. METHODS AND RESULTS: Patients with troponin-positive ACS
      (n=35) were randomized to 20 mg/day rosuvastatin therapy or to placebo treatment.
      Anti-inflammatory effects of rosuvastatin measured by lymphocyte intracellular
      cytokine production were taken before initiation of treatment and on days 1, 3,
      and 42. Compared with placebo, rosuvastatin treatment significantly reduced
      plasma concentrations of pro-inflammatory cytokines TNF-alpha and IFN-gamma at 72
      h. Rosuvastatin also induced a rapid and significant reduction of TNF-alpha and
      IFN-gamma production in stimulated T-lymphocytes at 72 h. When compared with
      placebo, rosuvastatin inhibited the Th-1-immune response measured at 72 h.
      CONCLUSION: Rosuvastatin exerts rapid immunomodulatory effects on the level of T
      cell activation in patients with ACS.

PMID- 17012300
TI  - Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg
      dose.
AB  - OBJECTIVES: The purpose of this study was to determine the tissue and
      corresponding serum concentration of tigecycline at selected time points in gall
      bladder, bile, colon, bone, synovial fluid (SF), lung and CSF in subjects
      undergoing surgical or medical procedures. METHODS: One hundred and four adult
      subjects (aged 24-83 years; 64 women, 40 men) received a single intravenous
      (i.v.) dose of tigecycline (100 mg infused over 30 min). Subjects were randomly
      assigned to one of four collection times at 4, 8, 12 and 24 h after the start of
      the infusion. For CSF, samples were collected at approximately 1.5 and 24 h after
      the start of the infusion. All subjects had serum samples collected before the
      administration of tigecycline, at the end of the infusion and at the time
      corresponding to tissue or body fluid collection. Drug concentrations in serum,
      tissues and body fluids were determined by LC/MS/MS. The area under the mean
      concentration-time curve from 0 to 24 h (AUC(0-24)) was determined for the
      comparison of systemic exposure between tissue or body fluid to serum. RESULTS:
      The mean serum concentrations of tigecycline were similar to those previously
      published. Tissue penetration, expressed as the ratio of AUC(0-24) in tissue or
      body fluid to serum, was 537 for bile, 23 for gall bladder, 2.6 for colon, 2.0
      for lung, 0.41 for bone, 0.31 for SF and 0.11 for CSF. CONCLUSIONS: A single 100
      mg dose of intravenous tigecycline produced considerably higher tissue/fluid
      concentrations in bile, gall bladder, colon and lung compared with simultaneous
      serum concentrations. On average, the systemic exposure of tigecycline in bone,
      SF and CSF ranged from 11% to 41% of serum concentrations. The results in bone
      are inconsistent with previous radiolabelled studies in animals and it is unclear
      if tight binding to bone (versus low bone uptake) or poor extraction of
      tigecycline for LC/MS/MS detection or both may have contributed to the
      differences we observed in humans.

PMID- 17012301
TI  - Combined antifungal therapy in a murine infection by Candida glabrata.
AB  - OBJECTIVES: To develop proper treatments for patients who do not respond to
      current antifungal treatments, we tested new combinations of antifungal drugs for
      treating disseminated infections by Candida glabrata in a murine model. METHODS:
      Mice were rendered neutropenic by intraperitoneal cyclophosphamide and
      intravenous 5-fluorouracil administration. The animals were infected
      intravenously with 2 x 10(8) cfu of C. glabrata. The efficacies of micafungin
      combined with amphotericin B, fluconazole or flucytosine, and of amphotericin B
      combined with fluconazole were evaluated by survival and tissue burden reduction.
      RESULTS AND CONCLUSIONS: Micafungin plus amphotericin B was the most effective
      combination at reducing tissue burden. Micafungin at 10 mg/kg combined with
      amphotericin B at 0.75, 1.5 or 3 mg/kg prolonged survival with respect to the
      monotherapies, but only the second combination showed a synergistic effect in
      reducing fungal load in spleen and kidney. Amphotericin B at 1.5 mg/kg combined
      with micafungin at 5, 10 or 20 mg/kg reduced tissue burden with respect to the
      monotherapies, but the effects of the three combinations were very similar. These
      results suggest that amphotericin B in combination with micafungin is promising
      for the treatment of disseminated C. glabrata infections.

PMID- 17012302
TI  - Survival of male breast cancer patients: a population-based study in Osaka,
      Japan.
AB  - BACKGROUND: Little information is available on the survival of male breast cancer
      patients because the disease is extremely rare in men. Recent studies indicated
      there were no gender-differences in the 5-year survival if patients' age and
      stage were matched. However, this problem has rarely been studied in Japan.
      METHODS: Using the Osaka Cancer Registry's data, the 5-year survival was analyzed
      based on the reported 19,869 cases who lived in Osaka Prefecture excluding Osaka
      City and were diagnosed in 1975-1997, or who resided in Osaka City and were
      diagnosed in 1993-1997, because reliable follow-up information was available for
      them. RESULTS: Breast cancer in males accounted for 0.49% of all cases during
      1975-1997. The 5-year relative survivals were 71.1% in men and 81.6% in women.
      The survival in males decreased over older groups due to a lower proportion of
      localized stage, but not in females. The survival of males in the regional stage
      was significantly lower than that of females (49.1 versus 73.7%, P<0.05).
      Survival of males has increased since 1980-1984, while it has been stable in
      females. Compared with the survival of patients diagnosed in 1975-1979, male
      patients diagnosed in 1995-1997 had a noticeably lower risk of death after
      adjusting for age and cancer stage. CONCLUSIONS: The results suggest male breast
      cancer patients at the regional stage had a worse 5-year survival rate compared
      to females. However, this gender-related difference seems to have disappeared
      with the increased survival of males during the 1990s. Further population-based
      studies are required with a greater number of male patients diagnosed after 1990.

PMID- 17012303
TI  - ACB-PCR measurement of K-ras codon 12 mutant fractions in livers of Big Blue rats
      treated with N-hydroxy-2-acetylaminofluorene.
AB  - K-ras codon 12 GGT-->GAT and GGT-->GTT mutations are the most frequently observed
      K-ras point mutations in human and rodent tumors and therefore are implicated in
      carcinogenesis for many tissues. Measurement of these mutations in rat models and
      human tissue could facilitate a more logical extrapolation of rodent
      tumorigenesis data to human disease. We have developed allele-specific
      competitive blocker PCR (ACB-PCR) assays for rat K-ras codon 12 GGT-->GTT and GGT
      ->GAT mutations that parallel the already published assays for human K-ras codon
      12 mutations. Liver K-ras codon 12 mutant allele fractions were measured in
      vehicle-treated and N-hydroxy-2-acetylaminofluorene (N-OH-AAF)-treated Big Blue
      rats. The average K-ras codon 12 GGT-->GTT mutant fraction (MF) for four control
      rats was 50 x 10(-6) (95% CI: 27 x 10(-6), 95 x 10(-6)) and for four treated rats
      was 165 x 10(-6) (95% CI: 87 x 10(-6), 312 x 10(-6)), indicating a 3.3-fold
      increase with treatment (95% CI: 1.3-8.1). The average MF of K-ras codon 12 GGT-
      >GAT for control rats was 1320 x 10(-6) (95% CI: 498 x 10(-6), 3500 x 10(-6)) and
      for treated rats was 8450 x 10(-6) (95% CI: 3180 x 10(-6), 22 400 x 10(-6)),
      indicating a 6.4-fold increase with treatment (95% CI: 1.6-25.4). These
      transgenic rats were part of a study that included analysis of liver lacI
      mutations. Although data from lacI determinations show that this compound induces
      mostly G-->T mutations, using the ACB-PCR method both K-ras codon 12 GGT-->GTT
      and GGT-->GAT MFs were significantly increased in treated rats versus control
      rats. This data raises the possibility that N-OH-AAF may not only induce
      mutations by a genotoxic mechanism, but also by amplification of both de novo and
      pre-existing K-ras mutation.

PMID- 17012304
TI  - Subcellular compartmentalization of glutathione: correlations with parameters of
      oxidative stress related to genotoxicity.
AB  - Glutathione (GSH) is a major component of the antioxidant defence system of
      mammalian cells and is found in subcellular pools within the cytoplasm, nucleus
      and mitochondria. To evaluate the relationships between these pools and
      parameters of oxidative stress related to genotoxicity, wild type (WT) and 8-oxo
      2'-deoxyguanosine glycosylase 1 (OGG1)-null (mOGG1(-/-)) mouse embryonic
      fibroblasts (MEF) were treated with buthionine sulphoximine (BSO; 0-1000 microM,
      24 h), an inhibitor of GSH biosynthesis. BSO treatment resulted in a
      concentration-dependent depletion of GSH from the cytoplasm, but depletion of
      mitochondrial and nuclear GSH occurred only at concentrations > or =100 microM.
      GSH levels were correlated with reactive oxygen species (ROS), lipid peroxidation
      (measured as the increase in the genotoxic end-product malondialdehyde (MDA)) and
      oxidative DNA modifications, measured as both frank DNA strand-breaks (FSB) and
      oxidized purine lesions (OxP) using the alkaline comet assay with
      formamidopyrimidine DNA glycosylase (FPG) modification; this system allowed for
      the identification of BSO-induced DNA modifications as primarily mutagenic 8-oxo
      2'-deoxyguanosine lesions. A number of significant correlations were observed.
      First, negative linear correlations were observed between mitochondrial GSH and
      ROS (r = -0.985 and r = -0.961 for WT and mOGG1(-/-) MEF, respectively), and
      mitochondrial GSH and MDA (r = -0.967 and r = -0.963 for WT and mOGG1(-/-) MEF,
      respectively). Second, positive linear correlations were observed between ROS and
      MDA (r = 0.996 and r = 0.935 for WT and mOGG1(-/-) MEF, respectively), and ROS
      and OxP (r = 0.938 and r = 0.981 for WT and mOGG1(-/-) MEF, respectively).
      Finally, oxidative DNA modifications displayed a negative linear correlation with
      nuclear GSH (r = -0.963 and -0.951 between nuclear GSH and FSB and OxP,
      respectively, for WT MEF and r = -0.960 between nuclear GSH and OxP in mOGG1(-/-)
      MEF), thus, demonstrating the genotoxic potential of compounds that deplete GSH.
      The findings highlight the critical roles of the mitochondrial and nuclear GSH
      pools in protecting cellular components, particularly DNA, from oxidative
      modification.

PMID- 17012305
TI  - Sleeping position, oxygen saturation and lung volume in convalescent, prematurely
      born infants.
AB  - OBJECTIVE: To determine whether the effects of sleeping position on lung volume
      and oxygenation are influenced by postmenstrual age (PMA) and oxygen dependency
      in convalescent prematurely born infants. DESIGN: Prospective study. SETTING:
      Tertiary neonatal unit. PATIENTS: 41 infants (21 oxygen dependent), median
      gestational age 28 weeks (range 24-31 weeks) and birth weight 1120 g (range 556
      1780 g). INTERVENTION: Infants were studied both supine and prone at two-weekly
      intervals from 32 weeks' PMA until discharge. Each posture was maintained for 1
      h. MAIN OUTCOME MEASURES: Pulse oximeter oxygen saturation (Spo(2)) was monitored
      continuously, and at the end of each hourly period functional residual capacity
      (FRC) was measured. RESULTS: Overall, lung volumes were higher in the prone
      position throughout the study period; there was no significant effect of PMA on
      lung volumes. Overall, Spo(2) was higher in the prone position (p = 0.02), and
      the effect was significant in the oxygen-dependent infants (p = 0.03) (mean
      difference in Spo(2) between prone and supine was 1.02%, 95% CI 0.11% to 1.92%),
      but not in the non-oxygen-dependent infants. There was no significant influence
      of PMA on Spo(2). CONCLUSION: In the present study, prone sleeping did not
      improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with
      no ongoing respiratory problems. However, the infants were monitored in each
      position for an hour, thus it is recommended that oxygen saturation should
      continue to be monitored after 32 weeks' PMA to be certain that longer periods of
      supine sleeping are not associated with loss of lung volume and hypoxaemia.

PMID- 17012306
TI  - Towards patient-centered health services in India--a scale to measure patient
      perceptions of quality.
AB  - OBJECTIVE: . (i) To develop a reliable and valid scale to measure in-patient and
      outpatient perceptions of quality in India and (ii) to identify aspects of
      perceived quality which have large effects on patient satisfaction. DESIGN: Cross
      sectional survey of health facilities and patients at clinics. SETTING: Primary
      health centers, community health centers, district hospitals, and female district
      hospitals in the state of Uttar Pradesh in north India. MAIN OUTCOME MEASURES:
      Internal consistency, validity, and factor structure of the scale are evaluated.
      The association between patient satisfaction and perceived quality dimensions is
      examined. RESULTS: A 16-item scale having good reliability and validity is
      developed. Five dimensions of perceived quality are identified-medicine
      availability, medical information, staff behavior, doctor behavior, and hospital
      infrastructure. Patient perceptions of quality at public health facilities are
      slightly better than neutral. Multivariate regression analysis results indicate
      that for outpatients, doctor behavior has the largest effect on general patient
      satisfaction followed by medicine availability, hospital infrastructure, staff
      behavior, and medical information. For in-patients, staff behavior has the
      largest effect followed by doctor behavior, medicine availability, medical
      information, and hospital infrastructure. CONCLUSIONS: The scale developed can be
      used to measure perceived quality at a range of facility types for outpatients
      and in-patients. Perceived quality at public facilities is only marginally
      favorable, leaving much scope for improvement. Better staff and physician
      interpersonal skills, facility infrastructure, and availability of drugs have the
      largest effect in improving patient satisfaction at public health facilities.

PMID- 17012307
TI  - IDEAS internal contamination database: a compilation of published internal
      contamination cases. A tool for the internal dosimetry community.
AB  - In the scope of the IDEAS project to develop General Guidelines for the
      Assessment of Internal Dose from Monitoring data, two databases were compiled.
      The IDEAS Bibliography database contains references dealing with problems related
      to cases of internal contamination. The IDEAS Internal Contamination Database now
      contains more than 200 cases of internal contamination. In the near future, the
      IDEAS Internal Contamination database will be made available to the internal
      dosimetry community. The database has several potential applications, including:
      training, testing biokinetic models, testing software for calculating intakes and
      doses from bioassay data, comparison of data from a new accidental intake with
      that from previous exposures to similar materials. The database is by no means
      complete, and this presentation is also an appeal for internal contamination
      cases to extend and update it.

PMID- 17012308
TI  - Comparison of stroke volume (SV) and stroke volume respiratory variation (SVV)
      measured by the axillary artery pulse-contour method and by aortic Doppler
      echocardiography in patients undergoing aortic surgery.
AB  - BACKGROUND: The goal of the study was to compare stroke volume (SV) and
      respiratory stroke volume variation (SVV) measured by pulse-contour analysis and
      aortic Doppler. METHODS: These were measured by pulse-contour analysis and
      thermodilution (PiCCO) and by aortic pulsed wave Doppler with transoesophageal
      echocardiography in patients undergoing abdominal aortic surgery. Simultaneous
      measurements were done at different times of surgery. All data were recorded on
      PiCCOwin software and videotape and analysed off-line by a blinded investigator.
      RESULTS: A total of 114 measurements were achieved in 20 patients. There was a
      good correlation and small bias between the PiCCO and the echo-Doppler values of
      the mean SV [r=0.885; bias=0.2 (8) ml], and between the minimum [r=0.842; bias=1
      (9) ml] and maximum SV [r=0.840; bias=2 (10) ml] values. CONCLUSIONS: There is a
      fair correlation between pulse-contour analysis and aortic Doppler for beat-by
      beat measurement of SV but not for calculation of SV respiratory ventilation.

PMID- 17012309
TI  - Hominoid-specific SPANXA/D genes demonstrate differential expression in
      individuals and protein localization to a distinct nuclear envelope domain during
      spermatid morphogenesis.
AB  - Human sperm protein associated with the nucleus on the X chromosome consists of a
      five-member gene family (SPANXA1, SPANXA2, SPANXB, SPANXC and SPANXD) clustered
      at Xq27.1. Evolved from an ancestral SPANX-N gene family (at Xq27 and Xp11)
      present in all primates as well as in rats and mice, the SPANXA/D family is
      present only in humans, bonobos, chimpanzees and gorillas. Among hominoid
      specific genes, the SPANXA/D gene family is considered to be undergoing rapid
      positive selection in its coding region. In this study, RT-PCR of human testis
      mRNA from individuals showed that, although all SPANXA/D genes are expressed in
      humans, differences are evident. In particular, SPANXC is expressed only in a
      subset of men. The SPANXa/d protein localized to the nuclear envelope of round,
      condensing and elongating spermatids, specifically to regions that do not
      underlie the developing acrosome. During spermiogenesis, the SPANXa/d-positive
      domain migrated into the base of the head as the redundant nuclear envelope that
      protrudes into the residual cytoplasm. Post-testicular modification of the
      SPANXa/d proteins was noted, as were PEST (proline, glutamic acid, serine, and
      threonine rich regions) domains. It is concluded that the duplication of the
      SPANX-N gene family that occurred 6-11 MYA resulted in a new gene family,
      SPANXA/D, that plays a role during spermiogenesis. The SPANXa/d gene products are
      among the few examples of X-linked nuclear proteins expressed following meiosis.
      Their localization to non-acrosomal domains of the nuclear envelope adjacent to
      regions of euchromatin and their redistribution to the redundant nuclear envelope
      during spermiogenesis provide a biomarker for the redundant nuclear envelope of
      spermatids and spermatozoa.

PMID- 17012310
TI  - Comparison of biological activity among nonfucosylated therapeutic IgG1
      antibodies with three different N-linked Fc oligosaccharides: the high-mannose,
      hybrid, and complex types.
AB  - The structure of asparagine-linked oligosaccharides attached to the antibody
      constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect
      the pharmacokinetics and antibody effector functions of antibody-dependent
      cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
      However, it is still unclear how differences in the N-linked oligosaccharide
      structures impact the biological activities of antibodies, especially those
      lacking core fucose. Here, we succeeded in generating core fucose-lacking human
      IgG1 antibodies with three different N-linked Fc oligosaccharides, namely, a high
      mannose, hybrid, and complex type, using the same producing clone, and compared
      their activities. Cultivation of an alpha-1,6-fucosyltransferase (FUT8) knockout
      Chinese hamster ovary cell line in the presence or absence of a glycosidase
      inhibitor (either swainsonine or kifunensine) yielded antibody production of each
      of the three types without contamination by the others. Two of three types of
      nonnaturally occurring atypical oligosaccharide IgG1, except the complex type,
      reduced the affinity for both human lymphocyte receptor IIIa (FcgammaRIIIa) and
      the C1q component of the complement, resulting in reduction of ADCC and CDC. The
      bulky structure of the nonreducing end of N-linked Fc oligosaccharides is
      considered to contribute the CDC change, whereas the structural change in the
      reducing end, i.e. the removal of core fucose, causes ADCC enhancement through
      improved FcgammaRIIIa binding. In the pharmacokinetic profile, although no
      significant difference of human neonatal Fc receptor (FcRn)-binding affinity was
      observed among the three types, the complex type showed longer serum half-lives
      than the other types irrespective of core fucosylation in mice, which also
      suggests the contribution of the nonreducing end structure. The present study
      provides basic information on the effects of core fucose-lacking N-linked Fc
      oligosaccharides on antibody biological activities.

PMID- 17012311
TI  - Ammonium recruitment and ammonia transport by E. coli ammonia channel AmtB.
AB  - To investigate substrate recruitment and transport across the Escherichia coli
      Ammonia transporter B (AmtB) protein, we performed molecular dynamics simulations
      of the AmtB trimer. We have identified residues important in recruitment of
      ammonium and intraluminal binding sites selective of ammonium, which provide a
      means of cation selectivity. Our results indicate that A162 guides translocation
      of an extraluminal ammonium into the pore lumen. We propose a mechanism for
      transporting the intraluminally recruited proton back to periplasm. Our mechanism
      conforms to net transport of ammonia and can explain why ammonia conduction is
      lost upon mutation of the conserved residue D160. We unify previous suggestions
      of D160 having either a structural or an ammonium binding function. Finally, our
      simulations show that the channel lumen is hydrated from the cytoplasmic side via
      the formation of single file water, while the F107/F215 stack at the inner-most
      part of the periplasmic vestibule constitutes a hydrophobic filter preventing
      AmtB from conducting water.

PMID- 17012312
TI  - A guide to accurate fluorescence microscopy colocalization measurements.
AB  - Biomolecular interactions are fundamental to the vast majority of cellular
      processes, and identification of the major interacting components is usually the
      first step toward an understanding of the mechanisms that govern various cell
      functions. Thus, statistical image analyses that can be performed on fluorescence
      microscopy images of fixed or live cells have been routinely applied for
      biophysical and cell biological studies. These approaches measure the fraction of
      interacting particles by analyzing dual color fluorescence images for colocalized
      pixels. Colocalization algorithms have proven to be effective, although the
      dynamic range and accuracy of these measurements has never been well established.
      Spatial image cross-correlation spectroscopy (ICCS), which cross-correlates
      spatial intensity fluctuations recorded in images from two detection channels
      simultaneously, has also recently been shown to be an effective measure of
      colocalization as well. Through simulations, imaging of fluorescent antibodies
      adsorbed on glass and cell measurements, we show that ICCS performs much better
      than standard colocalization algorithms at moderate to high densities of
      particles, which are often encountered in cellular systems. Furthermore, it was
      found that the density ratio between the two labeled species of interest plays a
      major role in the accuracy of the colocalization analysis. By applying a direct
      and systematic comparison between the standard, fluorescence microscopy
      colocalization algorithm and spatial ICCS, we show regimes where each approach is
      applicable, and more importantly, where they fail to yield accurate results.

PMID- 17012313
TI  - Passive stiffness in Drosophila indirect flight muscle reduced by disrupting
      paramyosin phosphorylation, but not by embryonic myosin S2 hinge substitution.
AB  - High passive stiffness is one of the characteristic properties of the
      asynchronous indirect flight muscle (IFM) found in many insects like Drosophila.
      To evaluate the effects of two thick filament protein domains on passive
      sarcomeric stiffness, and to investigate their correlation with IFM function, we
      used microfabricated cantilevers and a high resolution imaging system to study
      the passive IFM myofibril stiffness of two groups of transgenic Drosophila lines.
      One group (hinge-switch mutants) had a portion of the endogenous S2 hinge region
      replaced by an embryonic version; the other group (paramyosin mutants) had one or
      more putative phosphorylation sites near the N-terminus of paramyosin disabled.
      Both transgenic groups showed severely compromised flight ability. In this study,
      we found no difference (compared to the control) in passive elastic modulus in
      the hinge-switch group, but a 15% reduction in the paramyosin mutants. All
      results were corroborated by muscle fiber mechanics experiments performed on the
      same lines. The fact that myofibril elasticity is unaffected by hinge switching
      implies alternative S2 hinges do not critically affect passive sarcomere
      stiffness. In contrast, the mechanical defects observed upon disrupting
      paramyosin phosphorylation sites in Drosophila suggests that paramyosin
      phosphorylation is important for maintaining high passive stiffness in IFM
      myofibrils, probably by affecting paramyosin's interaction with other sarcomeric
      proteins.

PMID- 17012314
TI  - Sequence-specific solvent accessibilities of protein residues in unfolded protein
      ensembles.
AB  - Protein stability cannot be understood without the correct description of the
      unfolded state. We present here an efficient method for accurate calculation of
      atomic solvent exposures for denatured protein ensembles. The method used to
      generate the ensembles has been shown to reproduce diverse biophysical
      experimental data corresponding to natively and chemically unfolded proteins.
      Using a data set of 19 nonhomologous proteins containing from 98 to 579 residues,
      we report average accessibilities for all residue types. These averaged
      accessibilities are considerably lower than those previously reported for
      tripeptides and close to the lower limit reported by Creamer and co-workers. Of
      importance, we observe remarkable sequence dependence for the exposure to solvent
      of all residue types, which indicates that average residue solvent exposures can
      be inappropriate to interpret mutational studies. In addition, we observe smaller
      influences of both protein size and protein amino acid composition in the
      averaged residue solvent exposures for individual proteins. Calculating residue
      specific solvent accessibilities within the context of real sequences is thus
      necessary and feasible. The approach presented here may allow a more precise
      parameterization of protein energetics as a function of polar- and apolar-area
      burial and opens new ways to investigate the energetics of the unfolded state of
      proteins.

PMID- 17012315
TI  - Direct measurement of local chromatin fluidity using optical trap modulation
      force spectroscopy.
AB  - Chromatin assembly is condensed by histone tail-tail interactions and other
      nuclear proteins into a highly compact structure. Using an optical trap
      modulation force spectroscopy, we probe the effect of tail interactions on local
      chromatin fluidity. Chromatin fibers, purified from mammalian cells, are tethered
      between a microscope coverslip and a glass micropipette. Mechanical unzipping of
      tail interactions, using the micropipette, lead to the enhancement of local
      fluidity. This is measured using an intensity-modulated optically trapped bead
      positioned as a force sensor on the chromatin fiber. Enzymatic digestion of the
      histone tail interactions of tethered chromatin fiber also leads to a similar
      increase in fluidity. Our experiments show that an initial increase in the local
      fluidity precedes chromatin decompaction, suggesting possible mechanisms by which
      chromatin-remodeling machines access regulatory sites.

PMID- 17012316
TI  - Evaluation of elastic properties of atomistic DNA models.
AB  - A number of intriguing aspects in dynamics of double-helical DNA is related to
      the coupling between its macroscopic and microscopic states. A link between the
      elastic properties of long DNA chains and their atom-level dynamics can be
      established by comparing the worm-like chain model of polymer DNA with the
      conformational ensembles produced by molecular dynamics simulations. This problem
      is complicated by the complexity of the DNA structure, the small size of DNA
      fragments, and relatively short trajectory durations accessible in computer
      simulations of microscopic DNA dynamics. A careful study of all these aspects has
      been performed by using longer DNA fragments and increased durations of MD
      trajectories as compared to earlier such investigations. Special attention is
      paid to the necessary conditions and criteria of time convergence, and the
      possibility to increase the sampling by using constrained DNA models and
      simplified simulation conditions. It is found that dynamics of 25-mer duplexes
      with regular sequences agrees well with the worm-like chain theory and that
      accurate evaluation of DNA elastic parameters requires at least two turns of the
      double helix and approximately 20-ns duration of trajectories. Bond length and
      bond-angle constraints affect the estimates within numerical errors. In contrast,
      simplified treatment of solvation can strongly change the observed elastic
      parameters of DNA. The elastic parameters evaluated for AT- and GC-alternating
      duplexes reasonably agree with experimental data and suggest that, in different
      basepair sequences, the torsional and stretching elasticities vary stronger than
      the bending stiffness.

PMID- 17012317
TI  - Ab initio self-consistent x-ray absorption fine structure analysis for
      metalloproteins.
AB  - X-ray absorption fine structure is a powerful tool for probing the structures of
      metals in proteins in both crystalline and noncrystalline environments. Until
      recently, a fundamental problem in biological XAFS has been that ad hoc
      assumptions must be made concerning the vibrational properties of the amino acid
      residues that are coordinated to the metal to fit the data. Here, an automatic
      procedure for accurate structural determination of active sites of
      metalloproteins is presented. It is based on direct multiple-scattering
      simulation of experimental X-ray absorption fine structure spectra combining
      electron multiple scattering calculations with density functional theory
      calculations of vibrational modes of amino acid residues and the genetic
      algorithm differential evolution to determine a global minimum in the space of
      fitting parameters. Structure determination of the metalloprotein active site is
      obtained through a self-consistent iterative procedure with only minimal initial
      information.

PMID- 17012318
TI  - Changes in secondary structures and acidic side chains of melibiose permease upon
      cosubstrates binding.
AB  - Infrared difference spectroscopy analysis of the purified melibiose permease of
      Escherichia coli reconstituted into liposomes was carried out as a function of
      the presence of the two symporter substrates (Na(+), melibiose) in either H(2)O
      or in D(2)O media. Essentially, the data first show that addition of Na(+)
      induces appearance of peaks assigned to changes in the environment and/or
      orientation of alpha-helical domains of purified melibiose permease. Likewise,
      melibiose addition in the presence of Na(+) produces peaks corresponding to
      additional changes of alpha-helix environment or tilt. In addition to these
      changes, a pair of peaks (1599 (+) cm(-1)/1576 (-) cm(-1)) appearing in the Na(+)
      induced difference spectrum is assigned to the antisymmetric stretching of COO(-)
      groups, since they show practically no shift upon H/D exchange. It is proposed
      that these acidic groups participate in Na(+) co-ordination. A corresponding pair
      of peaks, again fairly insensitive to H/D substitution (1591 (-) cm(-1)/1567 (+)
      cm(-1)), appear in the melibiose-induced difference spectra, and may again be
      assigned to COO(-) groups. The latter carboxyl groups may correspond to part or
      all of the acidic residues interacting with Lys or Arg in the resting state that
      become free upon melibiose binding.

PMID- 17012319
TI  - Electron paramagnetic resonance oximetry as a quantitative method to measure
      cellular respiration: a consideration of oxygen diffusion interference.
AB  - Electron paramagnetic resonance (EPR) oximetry is being widely used to measure
      the oxygen consumption of cells, mitochondria, and submitochondrial particles.
      However, further improvement of this technique, in terms of data analysis, is
      required to use it as a quantitative tool. Here, we present a new approach for
      quantitative analysis of cellular respiration using EPR oximetry. The course of
      oxygen consumption by cells in suspension has been observed to have three
      distinct zones: pO(2)-independent respiration at higher pO(2) ranges, pO(2)
      dependent respiration at low pO(2) ranges, and a static equilibrium with no
      change in pO(2) at very low pO(2) values. The approach here enables one to
      comprehensively analyze all of the three zones together-where the progression of
      O(2) diffusion zones around each cell, their overlap within time, and their
      potential impact on the measured pO(2) data are considered. The obtained results
      agree with previously established methods such as high-resolution respirometry
      measurements. Additionally, it is also demonstrated how the diffusion limitations
      can depend on cell density and consumption rate. In conclusion, the new approach
      establishes a more accurate and meaningful model to evaluate the EPR oximetry
      data on cellular respiration to quantify related parameters using EPR oximetry.

PMID- 17012320
TI  - Interaction of toposome from sea-urchin yolk granules with dimyristoyl
      phosphatidylserine model membranes: a 2H-NMR study.
AB  - The yolk granule is the most abundant membrane-bound organelle present in sea
      urchin eggs and embryos. The major protein component of this organelle, toposome,
      accounts for approximately 50% of the total yolk protein and has been shown to be
      localized to the embryonic cell surface. Extensive characterization in several
      laboratories has defined a role for toposome in mediating membrane-membrane
      interactions. The current study expands the analysis of toposome-membrane
      interaction by defining toposome-induced changes to the lipid bilayer. The effect
      of toposome on the biophysical properties of phosphatidyl serine (PS)
      multibilayers was investigated using deuterium nuclear magnetic resonance and
      perdeuterated dimyristoyl PS (DMPS-d(54)). Toposome was found to have little
      effect on DMPS-d(54) chain orientational order in both the gel and liquid
      crystalline phases. Timescales for DMPS-d(54) reorientation were investigated
      using quadropole echo decay. Echo decay times were sensitive to toposome in the
      liquid-crystalline phase but not in the gel phase. Additional information about
      the perturbation of bilayer motions by toposome was obtained by analyzing its
      effect on the decay of Carr-Purcell-Meiboom-Gill echo trains. Collectively, these
      results suggest that toposome interacts peripherally with DMPS bilayers and that
      it increases the amplitude of lipid reorientation, possibly through local
      enhancement of bilayer curvature.

PMID- 17012321
TI  - A voltage-sensor water pore.
AB  - Voltage-sensor (VS) domains cause the pore of voltage-gated ion channels to open
      and close in response to changes in transmembrane potential. Recent experimental
      studies suggest that VS domains are independent structural units. This
      independence is revealed dramatically by a voltage-dependent proton-selective
      channel (Hv), which has a sequence homologous to the VS domains of voltage-gated
      potassium channels (Kv). Here we show by means of molecular dynamics simulations
      that the isolated open-state VS domain of the KvAP channel in a lipid membrane
      has a configuration consistent with a water channel, which we propose as a common
      feature underlying the conductance of protons, and perhaps other cations, through
      VS domains.

PMID- 17012322
TI  - Electrostatic potential energy within a protein monitored by metal charge
      dependent hydrogen exchange.
AB  - Hydrogen exchange measurements on Zn(II)-, Ga(III)-, and Ge(IV)-substituted
      Pyrococcus furiosus rubredoxin demonstrate that the log ratio of the base
      catalyzed rate constants (Delta log k(ex)) varies inversely with the distance out
      to at least 12 A from the metal. This pattern is consistent with the variation of
      the amide nitrogen pK values with the metal charge-dependent changes in the
      electrostatic potential. Fifteen monitored amides lie within this range,
      providing an opportunity to assess the strength of electrostatic interactions
      simultaneously at numerous positions within the structure. Poisson-Boltzmann
      calculations predict an optimal effective internal dielectric constant of 6. The
      largest deviations between the experimentally estimated and the predicted DeltapK
      values appear to result from the conformationally mobile charged side chains of
      Lys-7 and Glu-48 and from differential shielding of the peptide units arising
      from their orientation relative to the metal site.

PMID- 17012323
TI  - Role of the cytoplasmic domain in Anabaena sensory rhodopsin photocycling:
      vectoriality of Schiff base deprotonation.
AB  - Light-induced electric signals in intact E. coli cells generated by
      heterologously expressed full-length and C-terminally truncated versions of
      Anabaena sensory rhodopsin (ASR) demonstrate that the charge movements within the
      membrane-embedded part of the molecule are stringently controlled by the
      cytoplasmic domain. In particular, truncation inverts the direction of proton
      movement during Schiff base deprotonation from outward to cytoplasmic. Truncation
      also alters faster charge movements that occur before Schiff base deprotonation.
      Asp(217) as previously shown by FTIR serves as a proton acceptor in the truncated
      ASR but not in the full-length version, and its mutation to Asn restores the
      natural outward direction of proton movement. Introduction of a potential
      negative charge (Ser(86) to Asp) on the cytoplasmic side favors a cytoplasmic
      direction of proton release from the Schiff base. In contrast, mutation of the
      counterion Asp(75) to Glu reverses the photocurrent to the outward direction in
      the truncated pigment, and in both truncated and full-length versions accelerates
      Schiff base deprotonation more than 10-fold. The communication between the
      cytoplasmic domain and the membrane-embedded photoactive site of ASR demonstrated
      here is likely to derive from the receptor's use of a cytoplasmic protein for
      signal transduction, as has been suggested previously from binding studies.

PMID- 17012324
TI  - Enzyme kinetics above denaturation temperature: a temperature-jump/stopped-flow
      apparatus.
AB  - We constructed a "temperature-jump/stopped-flow" apparatus that allows us to
      study fast enzyme reactions at extremely high temperatures. This apparatus is a
      redesigned stopped-flow which is capable of mixing the reactants on a
      submillisecond timescale concomitant with a temperature-jump even as large as 60
      degrees C. We show that enzyme reactions that are faster than the denaturation
      process can be investigated above denaturation temperatures. In addition, the
      temperature-jump/stopped-flow enables us to investigate at physiological
      temperature the mechanisms of many human enzymes, which was impossible until now
      because of their heat instability. Furthermore, this technique is extremely
      useful in studying the progress of heat-induced protein unfolding. The
      temperature-jump/stopped-flow method combined with the application of structure
      specific fluorescence signals provides novel opportunities to study the stability
      of certain regions of enzymes and identify the unfolding-initiating regions of
      proteins. The temperature-jump/stopped-flow technique may become a breakthrough
      in exploring new features of enzymes and the mechanism of unfolding processes.

PMID- 17012325
TI  - Amino-acid solvation structure in transmembrane helices from molecular dynamics
      simulations.
AB  - Understanding the solvation of amino acids in biomembranes is an important step
      to better explain membrane protein folding. Several experimental studies have
      shown that polar residues are both common and important in transmembrane
      segments, which means they have to be solvated in the hydrophobic membrane, at
      least until helices have aggregated to form integral proteins. In this work, we
      have used computer simulations to unravel these interactions on the atomic level,
      and classify intramembrane solvation properties of amino acids. Simulations have
      been performed for systematic mutations in poly-Leu helices, including not only
      each amino acid type, but also every z-position in a model helix. Interestingly,
      many polar or charged residues do not desolvate completely, but rather retain
      hydration by snorkeling or pulling in water/headgroups--even to the extent where
      many of them exist in a microscopic polar environment, with hydration levels
      corresponding well to experimental hydrophobicity scales. This suggests that even
      for polar/charged residues a large part of solvation cost is due to entropy, not
      enthalpy loss. Both hydration level and hydrogen bonding exhibit clear position
      dependence. Basic side chains cause much less membrane distortion than acidic,
      since they are able to form hydrogen bonds with carbonyl groups instead of water
      or headgroups. This preference is supported by sequence statistics, where basic
      residues have increased relative occurrence at carbonyl z-coordinates. Snorkeling
      effects and N-/C-terminal orientation bias are directly observed, which
      significantly reduces the effective thickness of the hydrophobic core. Aromatic
      side chains intercalate efficiently with lipid chains (improving Trp/Tyr
      anchoring to the interface) and Ser/Thr residues are stabilized by hydroxyl
      groups sharing hydrogen bonds to backbone oxygens.

PMID- 17012326
TI  - All-trans retinol in rod photoreceptor outer segments moves unrestrictedly by
      passive diffusion.
AB  - The visual pigment protein of vertebrate rod photoreceptors, rhodopsin, contains
      an 11-cis retinyl moiety that is isomerized to all-trans upon light absorption.
      Subsequently, all-trans retinal is released from the protein and reduced to all
      trans retinol, the first step in the recycling of rhodopsin's chromophore group
      through the series of reactions that constitute the visual cycle. The
      concentration of all-trans retinol in photoreceptor outer segments can be
      monitored from its fluorescence. We have used two-photon excitation (720 nm) of
      retinol fluorescence and fluorescence recovery after photobleaching to
      characterize the mobility of all-trans retinol in frog photoreceptor outer
      segments. Retinol produced after rhodopsin bleaching moved laterally in the disk
      membrane bilayer with an apparent diffusion coefficient of 2.5 +/- 0.3 micro m(2)
      s(-1). The diffusion coefficient of exogenously added retinol was 3.2 +/- 0.5
      micro m(2) s(-1). These diffusion coefficients are in close agreement with those
      reported for lipids, suggesting that retinol is not tightly bound to protein
      sites that would be diffusing much more slowly in the plane of the membrane. In
      agreement with this interpretation, a fluorescent-labeled C-16 fatty acid
      diffused laterally with a similar diffusion coefficient, 2.2 +/- 0.2 micro m(2)
      s(-1). Retinol also moved along the length of the rod outer segment, with an
      apparent diffusion coefficient of 0.07 +/- 0.01 micro m(2) s(-1), again
      suggesting that it is not tightly bound to proteins that would confine it to the
      disks. The axial diffusion coefficient of exogenously added retinol was 0.05 +/-
      0.01 micro m(2) s(-1). In agreement with passive diffusion, the rate of axial
      movement was inversely proportional to the square of the length of the rod outer
      segment. Diffusion of retinol on the plasma membrane of the outer segment can
      readily account for the measured value of the axial diffusion coefficient, as the
      plasma membrane comprises approximately 1% of the total outer-segment membrane.
      The values of both the lateral and axial diffusion coefficients are consistent
      with most of the all-trans retinol in the outer segments moving unrestricted and
      not being bound to carrier proteins. Therefore, and in contrast to other steps of
      the visual cycle, there does not appear to be any specialized processing for all
      trans retinol within the rod outer segment.

PMID- 17012327
TI  - Diffusion of transcription factors can drastically enhance the noise in gene
      expression.
AB  - We study by Green's Function Reaction Dynamics the effect of the diffusive motion
      of repressor molecules on the noise in mRNA and protein levels for a gene that is
      under the control of a repressor. We find that spatial fluctuations due to
      diffusion can drastically enhance the noise in gene expression. After
      dissociation from the operator, a repressor can rapidly rebind to the DNA. Our
      results show that the rebinding trajectories are so short that, on this
      timescale, the RNA polymerase (RNAP) cannot effectively compete with the
      repressor for binding to the promoter. As a result, a dissociated repressor
      molecule will on average rebind many times, before it eventually diffuses away.
      These rebindings thus lower the effective dissociation rate, and this increases
      the noise in gene expression. Another consequence of the timescale separation
      between repressor rebinding and RNAP association is that the effect of spatial
      fluctuations can be described by a well-stirred, zero-dimensional, model by
      renormalizing the reaction rates for repressor-DNA (un) binding. Our results thus
      support the use of well-stirred, zero-dimensional models for describing noise in
      gene expression. We also show that for a fixed repressor strength, the noise due
      to diffusion can be minimized by increasing the number of repressors or by
      decreasing the rate of the open complex formation. Lastly, our results emphasize
      that power spectra are a highly useful tool for studying the propagation of noise
      through the different stages of gene expression.

PMID- 17012328
TI  - Curvature and hydrophobic forces drive oligomerization and modulate activity of
      rhodopsin in membranes.
AB  - G protein-coupled receptors (GPCRs) are essential components of cellular
      signaling pathways. They are the targets of many current pharmaceuticals and are
      postulated to dimerize or oligomerize in cellular membranes in conjunction with
      their functional mechanisms. We demonstrate using fluorescence resonance energy
      transfer how association of rhodopsin occurs by long-range lipid-protein
      interactions due to geometrical forces, yielding greater receptor crowding.
      Constitutive association of rhodopsin is promoted by a reduction in membrane
      thickness (hydrophobic mismatch), but also by an increase in protein/lipid molar
      ratio, showing the importance of interactions extending well beyond a single
      annulus of boundary lipids. The fluorescence data correlate with the pK(a) for
      the MI-to-MII transition of rhodopsin, where deprotonation of the retinylidene
      Schiff base occurs in conjunction with helical movements leading to activation of
      the photoreceptor. A more dispersed membrane environment optimizes formation of
      the MII conformation that results in visual function. A flexible surface model
      explains both the dispersal and activation of rhodopsin in terms of bilayer
      curvature deformation (strain) and hydrophobic solvation energy. The bilayer
      stress is related to the lateral pressure profile in terms of the spontaneous
      curvature and associated bending rigidity. Transduction of the strain energy
      (frustration) of the bilayer drives protein oligomerization and conformational
      changes in a coupled manner. Our findings illuminate the physical principles of
      membrane protein association due to chemically nonspecific interactions in fluid
      lipid bilayers. Moreover, they yield a conceptual framework for understanding how
      the tightly regulated lipid compositions of cellular membranes influence their
      protein-mediated functions.

PMID- 17012329
TI  - A rate equation approach to elucidate the kinetics and robustness of the TGF-beta
      pathway.
AB  - We present a rate equation model for the TGF-beta pathway in endothelial cells
      together with novel measurements. This pathway plays a prominent role in inter-
      and intracellular communication and subversion can lead to cancer, fibrosis
      vascular disorders, and immune diseases. The model successfully describes the
      kinetics of experimental data and also correctly predicts the behavior in
      experiments where the system is perturbed. A novel method in this context,
      simulated tempering, is used to fit the model parameters to the data. It provides
      an ensemble of high quality solutions, which are analyzed with clustering methods
      and display a hierarchical structure highlighting distinct parameter subspaces
      with biological interpretations. This analysis discriminates between different
      biological mechanisms to achieve a transient signal from a sustained TGF-beta
      input, where one mechanism is to use a negative feedback to turn the signal off.
      Further analysis in terms of parameter sensitivity reveals that this negative
      feedback loop in TGF-beta signaling renders the system global robustness. This
      sheds light upon the role of the Smad7 protein in this system.

PMID- 17012330
TI  - Spreading of neutrophils: from activation to migration.
AB  - Neutrophils rely on rapid changes in morphology to ward off invaders. Time
      resolved dynamics of spreading human neutrophils after activation by the
      chemoattractant fMLF (formyl methionyl leucyl phenylalanine) was observed by RICM
      (reflection interference contrast microscopy). An image-processing algorithm was
      developed to identify the changes in the overall cell shape and the zones of
      close contact with the substrate. We show that in the case of neutrophils, cell
      spreading immediately after exposure of fMLF is anisotropic and directional. The
      dependence of spreading area, A, of the cell as a function of time, t, shows
      several distinct regimes, each of which can be fitted as power laws (A ~ t(b)).
      The different spreading regimes correspond to distinct values of the exponent b
      and are related to the adhesion state of the cell. Treatment with cytochalasin-B
      eliminated the anisotropy in the spreading.

PMID- 17012331
TI  - The risk of infertility among hairdressers. Five-year follow-up of female
      hairdressers in a Danish national registry.
AB  - BACKGROUND: One in seven married couples is involuntarily infertile. Several
      chemical exposures in the work environment have been hypothesized to affect
      female reproduction, and some are present in products used in hairdressing and
      related trades. Recent Swedish findings indicate that employment in hairdressing
      poses a risk for female reproductive function. This study examined the possible
      association between work as a hairdresser and subsequent hospital contact due to
      female infertility. METHODS: A cohort of all women in Denmark aged 20-44 years on
      1 January 1998 (baseline) and registered as economically active hairdressers,
      according to national registers, was formed to calculate age-standardized risk
      ratios (RRs) for hospital contacts due to female infertility during a 5-year
      follow-up period. Hairdressers were compared to a standard population, that is,
      all economically active women in Denmark aged 20-44 years at baseline, and to
      women working as shop assistants. RESULTS: Sixty-eight cases of hospital contact
      due to female infertility were observed among the female hairdressers. On the
      basis of the standard population, the expected number was 73.27, which gives an
      observed RR of 0.928 (95% CI: 0.72-1.18). Hairdressers and shop assistants
      exhibited similar rates of hospital contact due to female infertility (1.01; 95%
      CI: 0.77-1.29). CONCLUSION: The findings are not corroborating the hypothesis
      that hairdressers are at increased risk of infertility, but small risks in the
      entire group or high risks in small subgroups may not be detected by the study.

PMID- 17012332
TI  - Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is
      altered by a substitution protocol without down-regulation in IVF patients.
AB  - BACKGROUND: The aim of this study was to analyse the effects of an estradiol
      (E(2))-progesterone substitution protocol on the endometrial expression of
      estrogen-sensitive genes during the peri-implantation period. METHODS: Peripheral
      blood and endometrial biopsies were obtained from 13 infertile women both in a
      natural cycle (NC), on days 5 and 7 after ovulation (NC5, NC7), and in an
      artificial (substituted) cycle (AC), on days 5 and 7 of progesterone addition
      (AC5, AC7). Estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) were
      assayed by immunohistochemistry. Matrix metalloproteinase-26 (MMP-26) mRNA and
      tissue inhibitor of metalloproteinase-4 (TIMP-4) mRNA were semiquantitatively
      assessed in tissue sections using in situ hybridization (ISH) and quantified in
      tissue extracts using real-time PCR. RESULTS: Levels of both E(2) and
      progesterone were higher in the peripheral blood in AC than in NC. Also on day
      AC5, expressions of ERalpha, PR and MMP-26 mRNA (focally) were increased in the
      epithelium and TIMP-4 mRNA in the stroma. Expression levels of these genes
      dropped significantly between AC5 and AC7, but not between NC5 and NC7.
      Abnormally high levels in AC5 samples suggest overstimulation with E(2), and the
      rapid decrease between AC5 and AC7 suggests overstimulation with progesterone.
      CONCLUSIONS: In ACs, increased levels of E(2) in the blood exaggerate the
      endometrial expression of estrogen-sensitive genes, whereas higher levels of
      progesterone in the blood in the secretory phase exaggerate the drop in
      expression of these genes. Dramatic variations in the gene expression may not be
      optimal for the implantation process.

PMID- 17012333
TI  - The effects of commonly prescribed drugs in patients with Alzheimer's disease on
      the rate of deterioration.
AB  - BACKGROUND: Prescribed drugs in patients with Alzheimer's disease may affect the
      symptomatic progression of their disease, both positively and negatively. AIM: To
      examine the effects of drugs on the progression of disease in a representative
      group of patients with Alzheimer's disease. METHODS: Patients with the diagnosis
      of probable Alzheimer's disease were recruited from the community. The prescribed
      drugs taken by 224 patients (mean age 82.3 years) were recorded at initial
      assessment and then correlated in logistic regression analysis with progression
      of the disease, defined as an increase of one point or more in the Global
      Deterioration Scale over the next 12-month period. RESULTS: Patients who were
      taking antipsychotic drugs and sedatives had a significantly higher risk of
      deterioration than those who were taking none (odds ratios (ORs) 2.74 (95%
      confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73),
      respectively). Higher risk of deterioration was observed in those who were taking
      both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7).
      Patients taking drugs licensed for dementia, drugs affecting the renin
      angiotensin system and statins had a significantly lower risk of deterioration
      than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to
      0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively).
      CONCLUSION: Our findings have implications for both clinicians and trialists.
      Most importantly, clinicians should carefully weigh any potential benefits of
      antipsychotics and benzodiazepines, especially in combination, against the risk
      of increased decline. Researchers need to be aware of the potential of not only
      licensed drugs for dementia but also drugs affecting the renin-angiotensin system
      and statins in reducing progression in clinical trials.

PMID- 17012334
TI  - Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in
      patients with medial temporal lobe epilepsy.
AB  - BACKGROUND: Structural neuroimaging studies have consistently shown a pattern of
      extra-hippocampal atrophy in patients with left and right drug-refractory medial
      temporal lobe epilepsy (MTLE). However, it is not yet completely understood how
      extra-hippocampal atrophy is related to hippocampal atrophy. Moreover, patients
      with left MTLE often exhibit more intense cognitive impairment, and subtle brain
      asymmetries have been reported in patients with left MTLE versus right MTLE but
      have not been explored in a controlled study. OBJECTIVES: To investigate the
      association between extra-hippocampal and hippocampal atrophy in patients with
      MTLE, and the effect of side of hippocampal atrophy on extra-hippocampal atrophy.
      METHODS: Voxel-based morphometry analyses of magnetic resonance images of the
      brain were performed to determine the correlation between regional extra
      hippocampal grey matter volume and hippocampal grey matter volume. The results
      from 36 patients with right and left MTLE were compared, and results from the two
      groups were compared with those from 49 healthy controls. RESULTS: Compared with
      controls, patients with MTLE showed a more intense correlation between
      hippocampal grey matter volume and regional grey matter volume in locations such
      as the contralateral hippocampus, bilateral parahippocampal gyri and frontal and
      parietal areas. Compared with right MTLE, patients with left MTLE exhibited a
      wider area of atrophy related to hippocampal grey matter loss, encompassing both
      the contralateral and ipsilateral hemispheres, particularly affecting the
      contralateral hippocampus. CONCLUSIONS: Our results suggest that left hippocampal
      atrophy is associated with a larger degree of extra-hippocampal atrophy. This may
      help to explain the more intense cognitive impairment usually observed in these
      patients.

PMID- 17012335
TI  - Treatment for obstructive sleep apnoea: effect on peripheral nerve function.
AB  - BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is suggested to be
      associated with peripheral nerve damage. A case-control study was conducted to
      provide further support to this observation. In a longitudinal intervention
      study, it was examined whether treatment for OSA has a possible beneficial effect
      on peripheral nerve function. METHODS: Participants were 23 patients with OSA and
      23 controls matched for age and body mass index (BMI), all without any known
      cause of peripheral nerve damage. The sensory nerve action potential (SNAP)
      amplitudes of both sural nerves were determined. After 6 months of treatment for
      OSA, treatment compliance was evaluated and nerve conduction studies were
      repeated. RESULTS: Patients with OSA had significantly lower mean (standard
      deviation) sural SNAP amplitudes than controls (6.3 (3.5) v 11.2 (5.0), p <
      0.001). Multivariate regression analysis including the variables age, BMI and
      Apnoea-Hypopnea Index (AHI) showed that both age (p < 0.01) and AHI (p < 0.05)
      were inversely related to the SNAP amplitude. On follow-up, the sural SNAP showed
      an increase of 2.6 mV on average (p < 0.001). Multivariate regression analysis
      including the variables age, BMI, AHI, pretreatment SNAP and treatment compliance
      identified only treatment compliance as being significantly related to the SNAP
      increase (p < or = 0.005). CONCLUSION: OSA is an independent risk factor for
      axonal dysfunction of peripheral sensory nerves. Impaired neural function is at
      least partly reversible with treatment for sleep apnoea.

PMID- 17012336
TI  - Deglutitive laryngeal closure in stroke patients.
AB  - BACKGROUND: Dysphagia has been reported in up to 70% of patients with stroke,
      predisposing them to aspiration and pneumonia. Despite this, the mechanism for
      aspiration remains unclear. AIMS: To determine the relationship between bolus
      flow and laryngeal closure during swallowing in patients with stroke and to
      examine the sensorimotor mechanisms leading to aspiration. METHODS: Measures of
      swallowing and bolus flow were taken from digital videofluoroscopic images in 90
      patients with stroke and 50 healthy adults, after repeated volitional swallows of
      controlled volumes of thin liquid. Aspiration was assessed using a validated
      Penetration-Aspiration Scale. Oral sensation was also measured by electrical
      stimulation at the faucial pillars. RESULTS: After stroke, laryngeal ascent was
      delayed (mean (standard deviation (SD)) 0.31 (0.06) s, p<0.001), resulting in
      prolongation of pharyngeal transit time (1.17 (0.07) s, p<0.001) without a
      concomitant increase in laryngeal closure duration (0.84 (0.04) s, p = 0.9). The
      delay in laryngeal elevation correlated with both the severity of aspiration (r =
      0.5, p<0.001) and oral sensation (r = 0.5, p<0.001). CONCLUSIONS: After stroke,
      duration of laryngeal delay and degree of sensory deficit are associated with the
      severity of aspiration. These findings indicate a role for sensorimotor
      interactions in control of swallowing and have implications for the assessment
      and management of dysphagia after stroke.

PMID- 17012337
TI  - Movement disorders in patients taking anticonvulsants.
AB  - BACKGROUND: A wide variety of movement disorders may occur as a consequence of
      the administration of antiepileptic drugs (AEDs). Although it has been suggested
      that the risk of parkinsonism is 10-fold higher in those taking valproate as
      compared with other AEDs, there have been no large, systematic trials assessing
      this. AIM: To establish more precisely the prevalence of and risk factors for
      developing parkinsonism associated with valproate use,and to assess the
      occurrence of movement disorders with the newer AEDs. METHODS: Patients with
      epilepsy were recruited from the Toronto Western Hospital Epilepsy Clinic
      (University of Toronto, Toronto, Ontario, Canada). Each patient was examined by a
      movement disorder specialist who was blinded to the treatment status of the
      patient. RESULTS: 201 patients were included. Postural tremor was the most common
      movement disorder (45%), followed by parkinsonism (4.5%). The odds of having
      parkinsonism were 5 times higher with valproate than with other AEDs. No single
      factor predicted the presence of parkinsonism; however, many (5/9) of the
      patients concurrently used other drugs or had comorbidities that could have
      caused or exacerbated parkinsonism. None of the newer AEDs were clearly
      associated with the presence of movement disorders; however, the numbers were too
      small to make a formal analysis. CONCLUSION: Although the risk of parkinsonism
      with valproate is higher than with other AEDs, it is lower than originally
      reported. The cases available were not enough to accurately comment on the
      prevalence of movement disorders with the newer AEDs.

PMID- 17012338
TI  - The relationship between cerebral Alzheimer's disease pathology and odour
      identification in old age.
AB  - BACKGROUND: Olfactory dysfunction is common in old age, but its basis is
      uncertain. OBJECTIVE: To test the hypothesis that difficulty in identifying
      odours in old age is related to the accumulation of Alzheimer's disease
      pathology. METHODS: As part of the Rush Memory and Aging Project, participants
      completed the 12-item Brief Smell Identification Test, a standard measure of
      odour identification. During a mean (standard deviation (SD)) of 2.2 (1.2) years
      of follow-up (range 0.2-4.9), 166 people died, with brain autopsies performed on
      129 (77.7%) people and neuropathological examinations completed on 77 (mean (SD)
      age at death 87.5 (5.9) years; median postmortem interval 6.1 h). From a uniform
      postmortem examination of multiple brain regions, summary measures of plaque and
      tangle pathology were derived on the basis of silver staining, and those of
      amyloid beta burden, tangle density and Lewy bodies on the basis of
      immunohistochemistry. RESULTS: Odour identification performance ranged from 0 to
      12 correct (mean (SD) 8.0 (2.6)). In analyses adjusted for age, sex and
      education, a composite measure of plaques and tangles accounted for >12% of the
      variation in odour identification. The association remained after controlling for
      dementia or semantic memory. Density of tau tangles was inversely related to
      odour identification. A similar effect for amyloid burden was attenuated after
      controlling for tangles. The association with odour identification was robust for
      tangles in the entorhinal cortex and CA1/subiculum area of the hippocampus, but
      not for tangles in other cortical sites. Lewy bodies, identified in 12.5%, were
      not related to odour identification, probably partly due to to their relative
      infrequency. CONCLUSION: The results suggest that difficulty in identifying
      familiar odours in old age is partly due to the accumulation of neurofibrillar
      pathology in central olfactory regions.

PMID- 17012339
TI  - Oops! Resolving social dilemmas in frontotemporal dementia.
AB  - OBJECTIVES: Our social cognition model posits that social knowledge and executive
      resources guide interpersonal decision making. We investigated this model by
      examining the resolution of standardised social dilemmas in patients with a
      social and executive disorder (SOC/EXEC) caused by frontotemporal dementia (FTD).
      METHODS: Patients with SOC/EXEC (n = 12) and those with progressive aphasia (APH,
      n = 14) completed measures requiring resolution of social dilemmas (Guilford's
      Cartoon Predictions Test), social cognition (theory of mind false belief
      vignettes and a behavioural rating measure of empathy) and executive measures of
      cognitive flexibility (Visual Verbal Test). Regression analysis related judgments
      of social dilemmas to cortical volume using voxel based morphometry of high
      resolution structural MRI. RESULTS: Patients with SOC/EXEC were impaired in
      judgments of social dilemmas as well as theory of mind, self-awareness of empathy
      and cognitive flexibility. Patients with APH were much less impaired in the
      social and cognitive measures. There were strong correlations among social
      dilemma, theory of mind and mental flexibility measures in patients with
      SOC/EXEC, and stepwise regression showed that mental flexibility was most
      predictive of social dilemma judgments. Social dilemma impairments in the
      SOC/EXEC sample correlated with cortical atrophy in the orbital frontal, superior
      temporal, visual association and posterior cingulate regions of the right
      hemisphere. CONCLUSIONS: Deficits in patients with SOC/EXEC in resolving social
      dilemmas are related to depleted executive resources and social knowledge that
      appear to arise from disease that interrupts a right frontal-temporal neural
      network crucial for mediating social cognition.

PMID- 17012340
TI  - Clinical features and predictive factors of intraventricular rupture in patients
      who have bacterial brain abscesses.
AB  - BACKGROUND: Intraventricular rupture of brain abscesses (IVRBA) remains a
      catastrophic and fatal complication of bacterial brain abscess (BBA). However, no
      information has been reported about the risk factors that are predictive of
      intraventricular rupture. METHODS: This study was undertaken to determine the
      potential risk factors that are predictive of intraventricular ruptures in
      patients with BBA but without intraventricular rupture when arriving at the
      hospital. A comparison is also made between patients who already have IVRBA at
      the time of admission (initial IVRBA) and those who have the episode during
      hospitalisation (subsequent IVRBA). RESULTS: 62 patients, including 45 who had
      initial IVRBA and 17 who had subsequent IVRBA, were examined. Stepwise logistic
      regression analysis showed that the adjusted risk of intraventricular rupture
      during hospitalisation for patients with multiloculated brain abscesses had an
      odds ratio (OR) of 4.2 (95% confidence interval (CI) 1.24 to 14.3; p = 0.02)
      compared with those without multiloculated brain abscesses (referent); a
      reduction of 1 mm in the distance between the ventricle and brain abscesses would
      increase the rupture rate by 10% (p = 0.006, OR 0.9, 95% CI 0.83 to 0.97).
      CONCLUSION: This study shows that if the abscess is deep seated, multiloculated
      and close to the ventricle wall, a reduction of 1 mm in the distance between the
      ventricle and brain abscesses will increase the rupture rate by 10%. Despite
      aggressive medical and surgical management shown in this series, many patients
      continue to progress poorly.

PMID- 17012341
TI  - Deep brain stimulation in the internal capsule and nucleus accumbens region:
      responses observed during active and sham programming.
AB  - BACKGROUND: Recently, anterior limb of the internal capsule and nucleus accumbens
      deep brain stimulation (DBS) has been used in the treatment of medication
      refractory obsessive-compulsive disorder (OCD). This region has been previously
      explored with lesion therapy, but with the advent of DBS there exists the
      possibility of monitoring the acute and chronic effects of electrical
      stimulation. The stimulation-induced benefits and side effects can be reversibly
      and blindly applied to a variety of locations in this region. OBJECTIVE: To
      explore the acute effects of DBS in the anterior limb of the internal capsule and
      nucleus accumbens region. METHODS: Ten total DBS leads in five patients with
      chronic and severe treatment-refractory OCD were tested. Patients were examined
      30 days after DBS placement and received either "sham" testing or actual testing
      of the acute effects of DBS (the alternative condition tested 30 days later).
      RESULTS: Pooled responses were reviewed for comparability of distribution using
      standard descriptive methods, and relationships between the variables of interest
      were sought using chi2 analysis. A total of 845 stimulation trials across the
      five patients were recorded and pooled. Of these 16% were elicited from sham
      stimulation and 17% from placebo (0 V stimulation). A comparison of active to
      sham trials showed that sham stimulation was not associated with significant side
      effects or responses from patients. Non-mood-related responses were found to be
      significantly associated with the ventral lead contacts (0 and 1) (p = 0.001).
      Responses such as taste, smell and smile were strongly associated with the most
      ventral lead positions. Similarly, physiological responses--for example,
      autonomic changes, increased breathing rate, sweating, nausea, cold sensation,
      heat sensation, fear, panic and panic episodes--were significantly associated
      with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered
      around the most ventral electrode (0). Acute stimulation resulted in either
      improved or worsened mood responses in both the dorsal and ventral regions of the
      anterior limb of the internal capsule. CONCLUSION: The acute effects of DBS in
      the region of the anterior limb of the internal capsule and nucleus accumbens,
      particularly when obtained in a blinded fashion, provide a unique opportunity to
      localise brain regions and explore circuitry.

PMID- 17012342
TI  - Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with
      cerebral biopsy findings and outcome of cerebrospinal fluid shunting.
AB  - OBJECTIVES: To elucidate the importance of clinically diagnosed cerebral
      comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on
      improvement after shunt surgery as well as concordance with parenchymal
      pathological changes described in frontal cerebral biopsy specimens. METHODS: In
      28 consecutive patients diagnosed with INPH and shunted according to clinical,
      radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were
      carefully registered, with special emphasis on cerebrovascular disease (CVD) and
      possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy
      specimen was obtained and subsequently analysed for pathological changes.
      RESULTS: One or several concurrent disorders were present in 89% of the patients,
      most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight
      patients presented both, diagnosed according to the criteria of the National
      Institute of Neurological and Communicative Disorders and Stroke and the
      Alzheimer's Disease and Related Disorders Association. The shunt success rate was
      33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease
      was found in the subgroups with no improvement or clinical deterioration compared
      with the patients improving after shunt surgery. The presence of CVD tended
      towards an unfavourable shunt outcome. The pathological parenchymal changes
      reflected the clinical diagnoses of comorbidity, and were described in about half
      of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n
      = 7) being the most common findings. However, no significant correlation was
      found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of
      cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not
      preclude clinical improvement after shunt operation. CONCLUSIONS: A high
      prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH,
      which was reflected, although less commonly, by similar neuropathological biopsy
      findings. No significant correlation was found between the presence of
      comorbidity and shunt outcome. The findings support the perception of INPH as a
      multiaetiological clinical entity, possibly overlapping pathophysiologically with
      CVD and Alzheimer's disease.

PMID- 17012343
TI  - Influence of subjective visual vertical misperception on balance recovery after
      stroke.
AB  - BACKGROUND: Subjective visual vertical (SVV) perception can be perturbed after
      stroke, but its effect on balance recovery is not yet known. AIM: To evaluate the
      influence of SVV perturbations on balance recovery after stroke. METHODS: 28
      patients (14 with a right hemisphere lesion (RHL) and 14 with a left hemisphere
      lesion (LHL)) were included, 5 were lost to follow-up. SVV perception was
      initially tested within 3 months after stroke, then at 6 months, using a luminous
      line, which the patients adjusted to the vertical position in a dark room. Mean
      deviation (V) and uncertainty (U), defined as the standard deviation of the SVV,
      were calculated for eight trials. Balance was initially assessed by the Postural
      Assessment Scale for Stroke (PASS), and at 6 months by the PASS (PASS6), a force
      platform (lateral and sagittal stability limits (LSL6 and SSL6)), the Rivermead
      Mobility Index (RMI6) and gait velocity (v6). Functional outcome was also
      assessed by the Functional Independence Measure at 6 months (FIM6). RESULTS: The
      scores for balance and for FIM6 were related to the initial V value: PASS6 (p =
      0.01, tau = -0.38); RMI6 (p = 0.002, tau = -0.48), LSL6 (p = 0.06, tau = -0.29),
      SSL6 (p = 0.004, tau = -0.43), v6 (p = 0.01, tau = -0.36) and FIM6 (p = 0.001,
      tau = -0.49), as well as to the initial U value: PASS6 (p = 0.03, tau = -0.32),
      RMI6 (p = 0.02, tau = -0.35), SSL6 (p = 0.005, tau = -0.43) and FIM6 (p = 0.01,
      tau = -0.38). CONCLUSIONS: Initial misperception of verticality was related to a
      poor score for balance after stroke. This relationship seems to be independent of
      motricity and neglect. Rehabilitation programmes should take into account
      verticality misperceptions, which could be an important factors influencing
      balance recovery after stroke.

PMID- 17012344
TI  - Dissecting carbohydrate-Cyanovirin-N binding by structure-guided mutagenesis:
      functional implications for viral entry inhibition.
AB  - The HIV-inactivating protein Cyanovirin-N (CV-N) is a cyanobacterial lectin that
      exhibits potent antiviral activity at nanomolar concentrations by interacting
      with high-mannose carbohydrates on viral glycoproteins. To date there is no
      molecular explanation for this potent virucidal activity, given the
      experimentally measured micromolar affinities for small sugars and the problems
      encountered with aggregation and precipitation of high-mannose/CV-N complexes.
      Here, we present results for two CV-N variants, CV-N(mutDA) and CV-N(mutDB),
      compare their binding properties with monomeric [P51G]CV-N (a stabilized version
      of wtCV-N) and test their in vitro activities. The mutations in CV-N(mutDA) and
      CV-N(mutDB) comprise changes in amino acids that alter the trimannose specificity
      of domain A(M) and abolish the sugar binding site on domain B(M), respectively.
      We demonstrate that carbohydrate binding via domain B(M) is essential for
      antiviral activity, whereas alterations in sugar binding specificity on domain
      A(M) have little effect on envelope glycoprotein recognition and antiviral
      activity. Changes in A(M), however, affect the cross-linking activity of CV-N.
      Our findings augment and clarify the existing models of CV-N binding to N-linked
      glycans on viral glycoproteins, and demonstrate that the nanomolar antiviral
      potency of CV-N is related to the constricted and spatially crowded arrangement
      of the mannoses in the glycan clusters on viral glycoproteins and not due to CV-N
      induced virus particle agglutination, making CV-N a true viral entry inhibitor.

PMID- 17012345
TI  - P2X receptor-mediated muscle pressor reflex in myocardial infarction.
AB  - A previous report from this laboratory demonstrated that the ATP-sensitive P2X
      receptor-mediated muscle pressor reflex was augmented in rats with heart failure
      (HF). The purpose of this study was to better understand the underlying
      mechanisms for this greater response in HF rats. We examined 1) responsiveness of
      the P2X receptor to alpha,beta-methylene ATP (alpha,beta-me-ATP), a P2X receptor
      agonist, in control and HF rats induced by myocardial infarction (MI); 2) the
      relationship between P2X-induced blood pressure response and left ventricular
      (LV) function; and 3) the expression of P2X receptors in the dorsal root ganglion
      (DRG) of control rats and rats with HF. Eight to 14 wk after coronary artery
      ligation, the severity of the MI was determined by echocardiography. In the first
      group of the experiment, alpha,beta-me-ATP (0.0625, 0.125, 0.25, and 0.5 mM) was
      injected into the arterial blood supply of the hindlimb muscles to evoke a
      pressor response in 17 decerebrated rats (6 controls, 6 small MIs with infarcts
      of the LV between 10 and 35%, and 5 large MIs with infarcts >35%). The P2X
      agonist increased blood pressure, and the effect was significantly accentuated in
      large MI rats compared with small MI rats and control rats. A significant
      correlation was observed between alpha,beta-me-ATP-evoked pressor response and
      the LV fractional shortening, an index of LV function. In the second group of the
      experiment, immunocytochemistry was used to examine the immunoreactivity of P2X
      receptor in the DRG neurons of small diameter fibers in six healthy control rats,
      five small MI, and five large MI rats. The percentage of P2X immunostaining
      positive neurons in the DRG was markedly greater in large MI rats (52% vs. 29% in
      controls and 34% in small MIs, P < 0.05). In conclusion, our findings demonstrate
      that 1) muscle afferent-mediated pressor response of P2X activation was
      exaggerated in MI animals, and the responsiveness was related to the degree of LV
      dysfunction; and 2) augmented reflex response was associated with upregulated P2X
      receptors in the DRG neurons of thin fiber afferent nerves following MI. The data
      suggest that P2X-mediated responsiveness in the processing of muscle afferent
      signals may have important implications for understanding cardiovascular
      responses to exercise in HF.

PMID- 17012346
TI  - Transcoronary gene transfer of SERCA2a increases coronary blood flow and
      decreases cardiomyocyte size in a type 2 diabetic rat model.
AB  - The Otsuka Long-Evans Tokushima fatty rat is an animal model of Type 2 diabetes
      mellitus (DM), which is characterized by diastolic dysfunction associated with
      decreased sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). The aim of this study
      was to examine whether gene transfer of SERCA2a can influence coronary blood flow
      and cardiomyocyte diameter in this model. DM rats were injected with adenovirus
      carrying SERCA2a (DM+SERCA) or beta-galactosidase gene (DM+betaGal). Coronary
      blood flow was measured in cross-circulated excised hearts 3 days after
      infection. Although in all groups coronary blood flow remained unchanged even if
      left ventricular (LV) volume or intracoronary Ca(2+) infusion was increased, the
      DM+SERCA group showed a sustained increase in coronary blood flow compared with
      the other groups. This result suggests that the sustained high coronary blood
      flow is a specific response in SERCA2a-overexpressed hearts. Although the LV
      weight-to-body weight ratio (LV/BW) and cardiomyocyte diameter were higher in the
      DM and DM+betaGal groups than in the non-DM group, in the DM+SERCA group, these
      measurements were restored to non-DM size. The percentages of collagen area in
      the three DM groups was significantly higher than results shown in non-DM rats,
      and there were no significant differences in collagen area percentage among the
      three DM groups. These results suggest that a lowered LV/BW by SERCA2a
      overexpression is due mainly to reduced size of cardiomyocytes without any
      changes in collagen area percentage. In conclusion, in DM failing hearts, SERCA2a
      gene transfer can increase coronary blood flow and reduce cardiomyocyte size
      without reduction in collagen production.

PMID- 17012347
TI  - Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by
      angiotensin II receptor blockade.
AB  - Stimulation of local renin-angiotensin system and increased levels of oxidants
      characterize the diabetic heart. Downregulation of ANG II type 1 receptors
      (AT(1)) and enhancement in PKC activity in the heart point out the role of AT(1)
      blockers in diabetes. The purpose of this study was to evaluate a potential role
      of an AT(1) blocker, candesartan, on abnormal Ca(2+) release mechanisms and its
      relationship with PKC in the cardiomyocytes from streptozotocin-induced diabetic
      rats. Cardiomyocytes were isolated enzymatically and then incubated with either
      candesartan or a nonspecific PKC inhibitor bisindolylmaleimide I (BIM) for 6-8 h
      at 37 degrees C. Both candesartan and BIM applied on diabetic cardiomyocytes
      significantly restored the altered kinetic parameters of Ca(2+) transients, as
      well as depressed Ca(2+) loading of sarcoplasmic reticulum, basal Ca(2+) level,
      and spatiotemporal properties of the Ca(2+) sparks. In addition, candesartan and
      BIM significantly antagonized the hyperphosphorylation of cardiac ryanodine
      receptor (RyR2) and restored the depleted protein levels of both RyR2 and FK506
      binding protein 12.6 (FKBP12.6). Furthermore, candesartan and BIM also reduced
      the increased PKC levels and oxidized protein thiol level in membrane fraction of
      diabetic rat cardiomyocytes. Taken together, these data demonstrate that AT(1)
      receptor blockade protects cardiomyocytes from development of cellular
      alterations typically associated with Ca(2+) release mechanisms in diabetes
      mellitus. Prevention of these alterations by candesartan may present a useful
      pharmacological strategy for the treatment of diabetic cardiomyopathy.

PMID- 17012348
TI  - Negative regulation of vascular smooth muscle cell migration by blood shear
      stress.
AB  - Vortex blood flow with reduced blood shear stress in a vein graft has been
      hypothesized to promote smooth muscle cell (SMC) migration and intimal
      hyperplasia, pathological events leading to vein graft restenosis. To demonstrate
      that blood shear stress regulates these processes, we developed a modified vein
      graft model where the SMC response to reduced vortex blood flow was compared with
      that of control vein grafts. Vortex blood flow induced SMC migration and
      neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood
      flow in the modified vein graft strongly suppressed these effects. A venous
      polymer implant with known fluid shear stress was employed to clarify the
      molecular mechanism of shear-dependent SMC migration in vivo. In the polymer
      implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2)
      and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day
      3 to day 5 and returned toward the control level from day 5 to day 10, with the
      peak phosphorylation associated with the maximal speed of SMC migration.
      Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2)
      significantly suppressed the phosphorylation of MLCK, suggesting a role for
      ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an
      inhibitor specific to MLCK) reduced shear stress-dependent SMC migration,
      resulting in an SMC distribution independent of fluid shear stress. These results
      suggest that fluid shear stress regulates SMC migration via the mediation of
      ERK1/2 and MLCK.

PMID- 17012349
TI  - Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by
      nitrite in isolated, perfused rat lungs.
AB  - Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase
      activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect
      of nitrite on the pulmonary circulation has not been well characterized. We
      explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and
      the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated
      vasodilation. As to method, isolated rat lungs were perfused with buffer, or
      buffer with RBCs, and subjected to repeated hypoxic challenges, with or without
      nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite
      concentrations of 7 muM and above. Nitrite inhibition of HPV was prevented by
      excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO.
      Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or
      xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition
      of HPV by nitrite (maximum nitrite concentration of approximately 35 muM)
      independent of perfusate Po(2). Degradation of nitrite was accelerated by hypoxia
      in the presence of RBCs but not during buffer perfusion. In conclusion, low
      micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and
      when RBC concentration is subphysiological. This effect is lost when RBC
      concentration approaches physiological levels, despite enhanced nitrite
      degradation in the presence of RBCs. These data suggest that, although deoxyHb
      may generate NO from nitrite, insufficient NO escapes the RBC to cause
      vasodilation in the pulmonary circulation under the dynamic conditions of blood
      flow through the lungs and that RBCs are net scavengers of NO.

PMID- 17012350
TI  - Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and
      numerical modeling.
AB  - Mice are widely used to study arterial disease in humans, and the pathogenesis of
      arterial diseases is known to be strongly influenced by hemodynamic factors. It
      is, therefore, of interest to characterize the hemodynamic environment in the
      mouse arterial tree. Previous measurements have suggested that many relevant
      hemodynamic variables are similar between the mouse and the human. Here we use a
      combination of Doppler ultrasound and MRI measurements, coupled with numerical
      modeling techniques, to characterize the hemodynamic environment in the mouse
      aortic arch at high spatial resolution. We find that the hemodynamically induced
      stresses on arterial endothelial cells are much larger in magnitude and more
      spatially uniform in the mouse than in the human, an effect that can be explained
      by fluid mechanical scaling principles. This surprising finding seems to be at
      variance with currently accepted models of the role of hemodynamics in
      atherogenesis and the known distribution of atheromatous lesions in mice.

PMID- 17012351
TI  - TRPC3 channels colocalize with Na+/Ca2+ exchanger and Na+ pump in axial component
      of transverse-axial tubular system of rat ventricle.
AB  - Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable,
      nonselective cation channels activated after stimulation of G protein-coupled
      membrane receptors linked to phospholipase C (PLC). Although the PLC/inositol
      phosphate signaling pathway is known to exist in heart, expression and
      subcellular distribution of TRPC channel proteins in ventricular myocardium have
      not been evaluated. Of the six members of the TRPC channel family examined here,
      only TRPC3 was found by Western blot analysis of membrane proteins from rodent or
      canine ventricle. Likewise, only TRPC3 was observed in immunofluorescence
      analysis of thin sections from rat ventricle. TRPC3 was also the only family
      member observed in neonatal rat ventricular myocytes in culture. In longitudinal
      sections of rat ventricle, TRPC3 was predominantly localized to the intercalated
      disk region of the myocyte. However, transverse sections through heart muscle or
      single isolated adult myocytes revealed TRPC3-specific labeling in a vast network
      of intracellular membranes, where it colocalized with the Na(+)-K(+)-ATPase (NKA)
      pump and the Na(+)/Ca(2+) exchanger (NCX) but not with the ryanodine receptor or
      the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pump. Reciprocal
      immunoprecipitation assays from rat or canine ventricle showed that TRPC3
      associates with NKA and NCX but not with the plasmalemmal Ca(2+)-ATPase pump.
      Immunoprecipitations from Sf9 insect cells heterologously expressing TRPC3, NKA,
      and NCX in various combinations revealed that NKA and NCX interact and that TRPC3
      and NCX interact, but that TRPC3 does not directly associate with NKA. Together,
      these results suggest that TRPC3 is localized in the ventricular myocyte to the
      axial component of the transverse-axial tubular system, where it exists in a
      signaling complex that includes NCX and NKA.

PMID- 17012352
TI  - Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity
      during static contraction.
AB  - The renal vasoconstriction induced by the sympathetic outflow during exercise
      serves to direct blood flow from the kidney toward the exercising muscles. The
      renal circulation seems to be particularly important in this regard, because it
      receives a substantial part of the cardiac output, which in resting humans has
      been estimated to be 20%. The role of group III mechanoreceptors in causing the
      reflex renal sympathetic response to static contraction remains an open question.
      To shed some light on this question, we recorded the renal sympathetic nerve
      responses to static contraction before and after injection of gadolinium into the
      arterial supply of the statically contracting triceps surae muscles of
      decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been
      shown to be a selective blocker of mechanogated channels in thin-fiber muscle
      afferents, which comprise the afferent arm of the exercise pressor reflex arc. In
      decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that
      gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and
      pressor responses to static contraction (60 s) after a latent period of 60 min;
      both responses recovered after a latent period of 120 min. We conclude that thin
      fiber mechanoreceptors supplying contracting muscle are involved in some of the
      renal vasoconstriction evoked by the exercise pressor reflex.

PMID- 17012353
TI  - Intracellular calcium handling in ventricular myocytes from mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is a lethal degenerative disease of skeletal
      muscle, characterized by the absence of the cytoskeletal protein dystrophin. Some
      DMD patients show a dilated cardiomyopathy leading to heart failure. This study
      explores the possibility that dystrophin is involved in the regulation of a
      stretch-activated channel (SAC), which in the absence of dystrophin has increased
      activity and allows greater Ca(2+) into cardiomyocytes. Because cardiac failure
      only appears late in the progression of DMD, we examined age-related effects in
      the mdx mouse, an animal model of DMD. Ca(2+) measurements using a fluorescent
      Ca(2+)-sensitive dye fluo-4 were performed on single ventricular myocytes from
      mdx and wild-type mice. Immunoblotting and immunohistochemistry were performed on
      whole hearts to determine expression levels of key proteins involved in
      excitation-contraction coupling. Old mdx mice had raised resting intracellular
      Ca(2+) concentration ([Ca(2+)](i)). Isolated ventricular myocytes from young and
      old mdx mice displayed abnormal Ca(2+) transients, increased protein expression
      of the ryanodine receptor, and decreased protein expression of serine-16
      phosphorylated phospholamban. Caffeine-induced Ca(2+) transients showed that the
      Na(+)/Ca(2+) exchanger function was increased in old mdx mice. Two SAC inhibitors
      streptomycin and GsMTx-4 both reduced resting [Ca(2+)](i) in old mdx mice,
      suggesting that SACs may be involved in the Ca(2+)-handling abnormalities in
      these animals. This finding was supported by immunoblotting data, which
      demonstrated that old mdx mice had increased protein expression of canonical
      transient receptor potential channel 1, a likely candidate protein for SACs. SACs
      may play a role in the pathogenesis of the heart failure associated with DMD.
      Early in the disease process and before the onset of clinical symptoms increased,
      SAC activity may underlie the abnormal Ca(2+) handling in young mdx mice.

PMID- 17012354
TI  - A simplified two-component model of blood pressure fluctuation.
AB  - We propose a simple moving-average (MA) model that uses the low-frequency (LF)
      component of the peroneal muscle sympathetic nerve spike rate (LF(spike rate))
      and the high-frequency (HF) component of respiration (HF(Resp)) to describe the
      LF neurovascular fluctuations and the HF mechanical oscillations in systolic
      blood pressure (SBP), respectively. This method was validated by data from eight
      healthy subjects (23-47 yr old, 6 male, 2 female) during a graded tilt (15
      degrees increments every 5 min to a 60 degrees angle). The LF component of SBP
      (LF(SBP)) had a strong baroreflex-mediated feedback correlation with LF(spike
      rate) (r = -0.69 +/- 0.05) and also a strong feedforward relation to LF(spike
      rate) [r = 0.58 +/- 0.03 with LF(SBP) delay (tau) = 5.625 +/- 0.15 s]. The HF
      components of spike rate (HF(spike rate)) and SBP (HF(SBP)) were not
      significantly correlated. Conversely, HF(Resp) and HF(SBP) were highly correlated
      (r = -0.79 +/- 0.04), whereas LF(Resp) and LF(SBP) were significantly less
      correlated (r = 0.45 +/- 0.08). The mean correlation coefficients between the
      measured and model-predicted LF(SBP) (r = 0.74 +/- 0.03) in the supine position
      did not change significantly during tilt. The mean correlation between the
      measured and model-predicted HF(SBP) was 0.89 +/- 0.02 in the supine position.
      R(2) values for the regression analysis of the model-predicted and measured LF
      and HF powers indicate that 78 and 91% of the variability in power can be
      explained by the linear relation of LF(spike rate) to LF(SBP) and HF(Resp) to
      HF(SBP). We report a simple two-component model using neural sympathetic and
      mechanical respiratory inputs that can explain the majority of blood pressure
      fluctuation at rest and during orthostatic stress in healthy subjects.

PMID- 17012355
TI  - Alterations in cerebral autoregulation and cerebral blood flow velocity during
      acute hypoxia: rest and exercise.
AB  - We examined the relationship between changes in cardiorespiratory and
      cerebrovascular function in 14 healthy volunteers with and without hypoxia
      [arterial O(2) saturation (Sa(O(2))) approximately 80%] at rest and during 60-70%
      maximal oxygen uptake steady-state cycling exercise. During all procedures,
      ventilation, end-tidal gases, heart rate (HR), arterial blood pressure (BP;
      Finometer) cardiac output (Modelflow), muscle and cerebral oxygenation (near
      infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAV;
      transcranial Doppler ultrasound) were measured continuously. The effect of
      hypoxia on dynamic cerebral autoregulation was assessed with transfer function
      gain and phase shift in mean BP and MCAV. At rest, hypoxia resulted in increases
      in ventilation, progressive hypocapnia, and general sympathoexcitation (i.e.,
      elevated HR and cardiac output); these responses were more marked during hypoxic
      exercise (P < 0.05 vs. rest) and were also reflected in elevation of the slopes
      of the linear regressions of ventilation, HR, and cardiac output with Sa(O(2)) (P
      < 0.05 vs. rest). MCAV was maintained during hypoxic exercise, despite marked
      hypocapnia (44.1 +/- 2.9 to 36.3 +/- 4.2 Torr; P < 0.05). Conversely, hypoxia
      both at rest and during exercise decreased cerebral oxygenation compared with
      muscle. The low-frequency phase between MCAV and mean BP was lowered during
      hypoxic exercise, indicating impairment in cerebral autoregulation. These data
      indicate that increases in cerebral neurogenic activity and/or sympathoexcitation
      during hypoxic exercise can potentially outbalance the hypocapnia-induced
      lowering of MCAV. Despite maintaining MCAV, such hypoxic exercise can potentially
      compromise cerebral autoregulation and oxygenation.

PMID- 17012356
TI  - Early experimental obesity is associated with coronary endothelial dysfunction
      and oxidative stress.
AB  - Obesity is independently associated with increased cardiovascular risk. However,
      since established obesity clusters with various cardiovascular risk factors,
      configuring the metabolic syndrome, the early effects of obesity on vascular
      function are still poorly understood. The current study was designed to evaluate
      the effect of early obesity on coronary endothelial function in a new animal
      model of swine obesity. As to method, juvenile domestic crossbred pigs were
      randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12
      wk. Coronary microvascular permeability and abdominal wall fat were determined by
      using electron beam computerized tomography. Epicardial endothelial function and
      oxidative stress were measured in vitro. Systemic oxidative stress, renin
      angiotensin activity, leptin levels, and parameters of insulin sensitivity were
      evaluated. As a result, HF pigs were characterized by abdominal obesity,
      hypertension, and elevated plasma lysophosphatidylcholine and leptin in the
      presence of increased insulin sensitivity. Coronary endothelium-dependent
      vasorelaxation was reduced in HF pigs and myocardial microvascular permeability
      increased compared with those values in normal pigs. Systemic redox status in HF
      pigs was similar to that in normal pigs, whereas the coronary endothelium
      demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH
      oxidase subunits, indicating increased tissue oxidative stress. In conclusion,
      the current study shows that early obesity is characterized by increased vascular
      oxidative stress and endothelial dysfunction in association with increased levels
      of leptin and before the development of insulin resistance and systemic oxidative
      stress. Vascular dysfunction is therefore an early manifestation of obesity and
      might contribute to the increased cardiovascular risk, independently of insulin
      resistance.

PMID- 17012358
TI  - A novel model of acute murine hindlimb ischemia.
AB  - The McGivney hemorrhoidal ligator (MHL), a band designed to cause tissue
      necrosis, is the preferred experimental tool to create hindlimb ischemia
      reperfusion (I/R) injury in rodents. This report defines and compares the ex vivo
      band tension exerted by MHL and orthodontic rubber bands (ORBs) along with select
      in vivo characteristics of I/R. As to method, ex vivo band tension was measured
      over relevant diameters using a tensiometer. In vivo assessment of murine limb
      perfusion during ischemia with ORB and MHL was compared using laser Doppler
      imaging and measurement of wet weight-to-dry weight ratio. Neuromuscular scoring
      and histological extent of muscle fiber injury after I/R with MHL and ORB were
      also compared. A dose-response curve, between the duration of ORB-induced I/R
      with both mitochondrial activity (methyl-thiazol-tetrazolium) or tail perfusion
      [laser Doppler imaging (LDI)], was generated. As a results, ex vivo measurements
      showed that ORB exerted significantly less force than the MHL. Despite less
      tension in ORB, in vivo testing of the ORB confirmed complete ischemia by both
      LDI and wet weight-to-dry weight ratio. After I/R, caused by ORB, there was
      significantly less neuromuscular dysfunction. Histological assessment confirmed
      similar degrees of muscle fiber injury after I/R with either the MHL or ORB.
      Increasing durations of ischemia created by the ORB followed by reperfusion
      significantly decreased mitochondrial activity and tail perfusion after 24 h of
      ischemia. In conclusions, ORB produced similar levels of tissue ischemia in
      murine models of limb I/R with fewer levels of nonspecific injury. ORB may be the
      preferred model for selected studies of limb I/R.

PMID- 17012357
TI  - Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac
      dysfunction and decreased survival only in males.
AB  - Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy
      (HCM) that is characterized by hypertrophy, histopathology, contractile
      dysfunction, and sudden death. The signaling pathways involved in the pathology
      of HCM have not been elucidated, and an unresolved question is whether blocking
      hypertrophic growth in HCM may be maladaptive or beneficial. To address these
      questions, a mouse model of HCM was crossed with an antihypertrophic mouse model
      of constitutive activated glycogen synthase kinase-3beta (caGSK-3beta). Active
      GSK-3beta blocked cardiac hypertrophy in both male and female HCM mice. However,
      doubly transgenic males (HCM/GSK-3beta) demonstrated depressed contractile
      function, reduced sarcoplasmic (endo) reticulum Ca(2+)-ATPase (SERCA) expression,
      elevated atrial natriuretic factor (ANF) expression, and premature death. In
      contrast, female HCM/GSK-3beta double transgenic mice exhibited similar cardiac
      histology, function, and survival to their female HCM littermates. Remarkably,
      dietary modification from a soy-based diet to a casein-based diet significantly
      improved survival in HCM/GSK-3beta males. These findings indicate that activation
      of GSK-3beta is sufficient to limit cardiac growth in this HCM model and the
      consequence of caGSK-3beta was sexually dimorphic. Furthermore, these results
      show that blocking hypertrophy by active GSK-3beta in this HCM model is not
      therapeutic.

PMID- 17012359
TI  - Nitric oxide preconditioning regulates endothelial monolayer integrity via the
      heat shock protein 90-soluble guanylate cyclase pathway.
AB  - Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low
      (physiological) NO concentrations often ameliorate cell injury. We tested the
      hypotheses that pretreatment of endothelial cells with low concentrations of NO
      (preconditioning) would prevent injury induced by high NO concentrations.
      Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to
      either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)-N-(2-hydroxy-2
      nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished
      by 24-h pretreatment with either 100 microM SNP, 10 microM spermine NONOate, or
      100 microM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured
      as the recovery rate of transendothelial electrical resistance, was delayed by 8
      h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h
      pretreatment with 100 microM SNP. NO preconditioning produced increased
      association and expression of soluble guanyl cyclase (sGC) and heat shock protein
      90 (HSP90). The protective effect of NO preconditioning, but not the injurious
      effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor
      (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with
      a low dose of NO donor accelerates repair and maintains endothelial integrity via
      a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role
      in the protective effects of NO-generating drugs from injurious stimuli.

PMID- 17012360
TI  - Intracellular sodium determines frequency-dependent alterations in contractility
      in hypertrophied feline ventricular myocytes.
AB  - Hypertrophy and failure (H/F) in humans and large mammals are characterized by a
      change from a positive developed force-frequency relationship (+FFR) in normal
      myocardium to a flattened or negative developed force-frequency relationship (
      FFR) in disease. Altered Ca(2+) homeostasis underlies this process, but the role
      of intracellular Na(+) concentration ([Na(+)](i)) in H/F and frequency-dependent
      contractility reserve is unclear. We hypothesized that altered [Na(+)](i) is
      central to the -FFR response in H/F feline myocytes. Aortic constriction caused
      left ventricular hypertrophy (LVH). We found that as pacing rate was increased,
      contraction magnitude was maintained in isolated control myocytes (CM) but
      decreased in LVH myocytes (LVH-M). Quiescent LVH-M had higher [Na(+)](i) than CM
      (LVH-M 13.3 +/- 0.3 vs. CM 8.9 +/- 0.2 mmol/l; P < 0.001) with 0.5-Hz pacing (LVH
      M 14.9 +/- 0.5 vs. CM 10.8 +/- 0.4 mmol/l; P < 0.001) but were not different at
      2.5 Hz (17.0 +/- 0.7 vs. control 16.0 +/- 0.7 mmol/l; not significant).
      [Na(+)](i) was altered by patch pipette dialysis to define the effect of
      [Na(+)](i) on contraction magnitude and action potential (AP) wave shape at slow
      and fast pacing rates. Using AP clamp, we showed that LVH-M require increased
      [Na(+)](i) and long diastolic intervals to maintain normal shortening. Finally,
      we determined the voltage dependence of contraction for Ca(2+) current (I(Ca))
      triggered and Na(+)/Ca(2+) exchanger-mediated contractions and showed that there
      is a greater [Na(+)](i) dependence of contractility in LVH-M. These data show
      that increased [Na(+)](i) is essential for maintaining contractility at slow
      heart rates but contributes to small contractions at fast rates unless rate
      dependent AP shortening is prevented, suggesting that altered [Na(+)](i)
      regulation is a critical contributor to abnormal contractility in disease.

PMID- 17012362
TI  - Acute modulation of PP2a and troponin I phosphorylation in ventricular myocytes:
      studies with a novel PP2a peptide inhibitor.
AB  - The present study demonstrates that acute activation with either beta-adrenergic
      receptor agonists or H(2)O(2) treatment increases protein phosphatase 2a (PP2a)
      activity in ventricular myocytes. PP2a activation occurs concomitant with an
      increase in methylation of PP2a, changes in localization of a PP2a targeting
      subunit PP2aB56alpha, and a decrease in phosphorylation of PP2a substrates, such
      as troponin I (TnI) and ERK in ventricular myocytes. Okadaic acid, a well
      established pharmacological inhibitor of PP2a, and the peptide Thr-Pro-Asp-Tyr
      Phe-Leu (TPDYFL) were used to block PP2a methylation, localization, and
      phosphorylations. TPDYFL is a highly conserved sequence of the PP2a catalytic
      subunit COOH-terminus. Specifically, both okadaic acid and the peptide increased
      beta-adrenergic-cAMP-dependent phosphorylation of TnI and blocked the beta
      adrenergic-cAMP-dependent translocation of PP2aB56alpha. TPDYFL, but not a
      scrambled version of this sequence, blocked H(2)O(2)-induced changes in PP2a
      methylation and TnI dephosphorylation. Okadaic acid produces similar inhibition
      of H(2)O(2) effects. Thus we propose that the novel peptide TPDYFL acts as an
      inhibitor of PP2a activity and may be a useful tool to increase our understanding
      of how PP2a is regulated and the role of PP2a in a variety of physiological and
      pathological processes. In addition, the present study is consistent with acute
      beta-adrenergic receptor activation and H(2)O(2) exposure, simultaneously
      activating kinases and PP2a to work on common substrates, such as TnI. We
      hypothesize that dual activation of opposing enzymes provides for a tighter
      regulation of substrate phosphorylations in ventricular myocytes.

PMID- 17012361
TI  - Interstitial K+ concentration in active muscle after myocardial infarction.
AB  - Previous work demonstrated that Na(+)-K(+) pump activity within skeletal muscle
      is attenuated in myocardial infarction (MI). This may lead to enhanced
      interstitial K(+) concentration ([K(+)](o)) in the muscle. We tested the
      hypothesis that [K(+)](o) rises with muscle contraction and that, in rats with
      MI, the rate of rise in [K(+)](o) is greater than it is in control animals.
      Microdialysis probes were inserted in the skeletal muscle of six healthy control
      and six MI rats. The ends of the probes were then attached to the K(+)
      electrodes, and [K(+)](o) was continuously measured. Muscle contraction was
      induced by electrical stimulation of the sciatic nerves for 1 min. Stimulation at
      1 and 3 Hz increased muscle [K(+)](o) by 14.2% and 44.7% in controls and by 22.9%
      and 62.8% in MI rats (P < 0.05 vs. controls), respectively. When ouabain, an
      inhibitor of Na(+)-K(+) pump, was added to the perfusate, muscle [K(+)](o) rose
      significantly. This effect of ouabain was significantly attenuated in MI animals.
      In conclusion, when compared with that in control animals, an increase of
      [K(+)](o) in exercising muscle is augmented in MI rats, likely due to an
      attenuation of Na(+)-K(+) pump activity.

PMID- 17012363
TI  - Evaluation of transmural distribution of viable muscle by myocardial strain
      profile and dobutamine stress echocardiography.
AB  - Transmural distribution of viable myocardium in the ischemic myocardium has not
      been quantified and fully elucidated. To address this issue, we evaluated
      transmural myocardial strain profile (TMSP) in dogs with myocardial infarction
      using a newly developed tissue strain imaging. TMSP was obtained from the
      posterior wall at the epicardial left ventricular short-axis view in 13
      anesthetized open-chest dogs. After control measurements, the left circumflex
      coronary artery was occluded for 90 min to induce subendocardial infarction
      (SMI). Subsequently, latex microbeads (90 microm) were injected in the same
      artery to create transmural infarction (TMI). In each stage, measurements were
      done before and after dobutamine challenge (10 microg.kg(-1).min(-1) for 10 min)
      to estimate transmural myocardial viability. Strain in the subendocardium in the
      control stage increased by dobutamine (from 53.6 +/- 17.1 to 73.3 +/- 21.8%, P <
      0.001), whereas that in SMI and TMI stages was almost zero at baseline and did
      not increase significantly by dobutamine [from 0.8 +/- 8.8 to 1.3 +/- 7.0%, P =
      not significant (NS) for SMI, from -3.9 +/- 5.6 to -1.9 +/- 6.0%, P = NS for
      TMI]. Strain in the subepicardium increased by dobutamine in the control stage
      (from 23.9 +/- 6.1 to 26.3 +/- 6.4%, P < 0.05) and in the SMI stage (from 12.4 +/
      7.3 to 27.1 +/- 8.8%, P < 0.005), whereas that in the TMI stage did not change
      (from -1.0 +/- 7.8 to -0.7 +/- 8.3%, P = NS). In SMI, the subendocardial
      contraction was lost, but the subepicardium showed a significant increase in
      contraction with dobutamine. However, in TMI, even the subepicardial increase was
      not seen. Assessment of transmural strain profile using tissue strain imaging was
      a new and useful method to estimate transmural distribution of the viable
      myocardium in myocardial infarction.

PMID- 17012364
TI  - Role of internalization of M2 muscarinic receptor via clathrin-coated vesicles in
      desensitization of the muscarinic K+ current in heart.
AB  - In the heart, ACh activates the ACh-activated K(+) current (I(K,ACh)) via the
      M(2) muscarinic receptor. The relationship between desensitization of I(K,ACh)
      and internalization of the M(2) receptor has been studied in rat atrial cells. On
      application of the stable muscarinic agonist carbachol for 2 h, I(K,ACh) declined
      by approximately 62% with time constants of 1.5 and 26.9 min, whereas
      approximately 83% of the M(2) receptor was internalized from the cell membrane
      with time constants of 2.9 and 51.6 min. Transfection of the cells with beta
      adrenergic receptor kinase 1 (G protein-receptor kinase 2) and beta-arrestin 2
      significantly increased I(K,ACh) desensitization and M(2) receptor
      internalization during a 3-min application of agonist. Internalized M(2) receptor
      in cells exposed to carbachol for 2 h was colocalized with clathrin and not
      caveolin. It is concluded that a G protein-receptor kinase 2- and beta-arrestin 2
      dependent internalization of the M(2) receptor into clathrin-coated vesicles
      could play a major role in I(K,ACh) desensitization.

PMID- 17012365
TI  - Disease emergence in multi-host epidemic models.
AB  - Most pathogens are capable of infecting multiple hosts. These multiple hosts
      provide many avenues for the disease to emerge. In this investigation, we
      formulate and analyse multi-host epidemic models and determine conditions under
      which the disease can emerge. In particular, SIS and SIR epidemic models are
      formulated for a pathogen that can infect n different hosts. The basic
      reproduction number is computed and shown to increase with n, the number of hosts
      that can be infected. Therefore, the possibility of disease emergence increases
      with the number of hosts infected. The SIS model for two hosts is studied in
      detail. Necessary and sufficient conditions are derived for the global stability
      of an endemic equilibrium. Numerical examples illustrate the dynamics of the two-
      and three-host epidemic models. The models have applications to hantavirus in
      rodents and other zoonotic diseases with multiple hosts.

PMID- 17012366
TI  - A prospective study of injury incidence among North Carolina high school
      athletes.
AB  - Sports-related injuries are an issue of concern in high school sports athletes. A
      prospective cohort study of injury risk factors was conducted from 1996 to 1999
      among varsity high school athletes in 12 sports in 100 North Carolina high
      schools. Data were collected by trained school personnel. Unadjusted and adjusted
      incidence rates and rate ratios were estimated using Poisson regression models.
      The overall rate of injury was 2.08 per 1,000 athlete-exposures (95% confidence
      interval (CI): 1.79, 2.41). At 3.54 per 1,000 athlete-exposures (95% CI: 2.87,
      4.37), football had the highest rate of injury of all sports. The adjusted rate
      ratio for athletes with a history of injury, compared with those without a prior
      injury, was 1.94 (95% CI: 1.69, 2.22). The injury rate rose with each year of
      playing experience (rate ratio=1.06, 95% CI: 1.01, 1.12). In a subanalysis
      restricted to gender-comparable sports, boys had a higher rate of injury than did
      girls (rate ratio=1.33, 95% CI: 0.99, 1.79). All other factors did not appear to
      be independent predictors of the injury rate. The influence of prior injury
      suggests that proper rehabilitation and primary prevention of the initial injury
      are important strategies for injury control.

PMID- 17012367
TI  - c-Src interacts with and phosphorylates RelA/p65 to promote thrombin-induced ICAM
      1 expression in endothelial cells.
AB  - The procoagulant thrombin promotes polymorphonuclear leukocyte (PMN) adhesion to
      endothelial cells by a mechanism involving expression of intercellular adhesion
      molecule-1 (ICAM-1) via an NF-kappaB-dependent pathway. We now provide evidence
      that activation of c-Src is crucial in signaling thrombin-induced ICAM-1
      expression via tyrosine phosphorylation of RelA/p65. Stimulation of human
      umbilical vein endothelial cells with thrombin resulted in a time-dependent
      activation of c-Src, with maximal activation occurring at 30 min after thrombin
      challenge. Inhibition of c-Src by pharmacological and genetic approaches impaired
      thrombin-induced NF-kappaB-dependent reporter activity and ICAM-1 expression.
      Analysis of the NF-kappaB pathway revealed that the effect of c-Src inhibition
      occurred independently of IkappaBalpha degradation and NF-kappaB DNA binding
      function and was not associated with exchange of NF-kappaB dimers.
      Phosphorylation of RelA/p65 at Ser(536), an event mediating the transcriptional
      activity of DNA-bound RelA/p65, was also insensitive to c-Src inhibition.
      Interestingly, thrombin induced association of c-Src with RelA/p65, and
      inhibition of c-Src prevented this response, indicating that this interaction is
      contingent on activation of c-Src. We also observed that thrombin induced
      tyrosine phosphorylation of RelA/p65, and this phosphorylation was lost upon
      inhibition of c-Src, consistent with the requirement of activated c-Src for
      interaction with RelA/p65. These data implicate an important role of c-Src in
      phosphorylating RelA/p65 to promote the transcriptional activity of NF-kappaB and
      thereby ICAM-1 expression in endothelial cells.

PMID- 17012368
TI  - CFTR is a modulator of airway inflammation.

PMID- 17012369
TI  - Resealing of endothelial junctions by focal adhesion kinase.
AB  - Endothelial cell (EC) junctions determine vascular barrier properties and are
      subject to transient opening to allow liquid flux from blood to tissue. Although
      EC junctions open in the presence of permeability-enhancing factors, including
      oxidants, the mechanisms by which they reseal remain inadequately understood. To
      model opening and resealing of EC junctions in the presence of an oxidant, we
      quantified changes in H(2)O(2)-induced transendothelial resistance (TER) in
      monolayers of rat lung microvascular EC. During a 30-min exposure, H(2)O(2) (100
      microM) decreased TER for an initial approximately 10 min, indicating junctional
      opening. Subsequently, despite continuous presence of H(2)O(2), TER recovered to
      baseline, indicating the activation of junctional resealing mechanisms. These
      bimodal TER transients matched the time course of loss and then gain of E
      cadherin at EC junctions. The timing of the TER decrease matched the onset of
      focal adhesion formation, while F-actin increase at the cell periphery occurred
      with a time course that complemented the recovery of peripheral E-cadherin. In
      monolayers expressing a focal adhesion kinase (FAK) mutant (del-FAK) that
      inhibits FAK activity, the initial H(2)O(2)-induced junctional opening was
      present, although the subsequent junctional recovery was blocked. Expression of
      transfected E-cadherin was evident at the cell periphery of wild-type but not del
      FAK-expressing EC. E-cadherin overexpression in del-FAK-expressing EC failed to
      effect major rescue of the junctional resealing response. These findings indicate
      that in oxidant-induced EC junction opening, FAK plays a critical role in
      remodeling the adherens junction to reseal the barrier.

PMID- 17012370
TI  - Involvement of microtubules, p38, and Rho kinases pathway in 2-methoxyestradiol
      induced lung vascular barrier dysfunction.
AB  - 2-Methoxyestradiol (2ME), a promising anti-tumor agent, is currently tested in
      phase I/II clinical trial to assess drug tolerance and clinical effects. 2ME is
      known to affect microtubule (MT) polymerization rather than act through estrogen
      receptors. We hypothesized that 2ME, similar to other MT inhibitors, disrupts
      endothelial barrier properties. We show that 2ME decreases transendothelial
      electrical resistance and increases FITC-dextran leakage across human pulmonary
      artery endothelial monolayer, which correlates with 2ME-induced MT
      depolymerization. Pretreatment of endothelium with MT stabilizer taxol
      significantly attenuates the decrease in transendothelial resistance. 2ME
      treatment results in the induction of F-actin stress fibers, accompanied by the
      increase in myosin light chain (MLC) phosphorylation. The experiments with Rho
      kinase (ROCK) and MLC kinase inhibitors and ROCK small interfering RNA (siRNA)
      revealed that increase in MLC phosphorylation is attributed to the ROCK
      activation rather than MLC kinase activation. 2ME induces significant ERK1/2,
      p38, and JNK phosphorylation and activation; however, only p38 activation is
      relevant to the 2ME-induced endothelial hyperpermeability. p38 activation is
      accompanied by a marked increase in MAPKAP2 and 27-kDa heat shock protein (HSP27)
      phosphorylation level. Taxol significantly decreases p38 phosphorylation and
      activation in response to 2ME stimulation. Vice versa, p38 inhibitor SB203580
      attenuates MT rearrangement in 2ME-challenged cells. Together, these results
      indicate that 2ME-induced barrier disruption is governed by MT depolymerization
      and p38- and ROCK-dependent mechanisms. The fact that certain concentrations of
      2ME induce endothelial hyperpermeability suggests that the issue of the maximum
      tolerated dose of 2ME for cancer treatment should be addressed with caution.

PMID- 17012371
TI  - Legionella pneumophila-induced PKCalpha-, MAPK-, and NF-kappaB-dependent COX-2
      expression in human lung epithelium.
AB  - Legionella pneumophila causes community- and hospital-acquired pneumonia. Lung
      airway and alveolar epithelial cells comprise an important barrier against
      airborne pathogens. Cyclooxygenase (COX) and microsomal PGE(2) synthase-1 (mPGES
      1)-derived prostaglandins like prostaglandin E(2) (PGE(2)) are considered as
      important regulators of lung function. Herein we tested the hypothesis that L.
      pneumophila induced COX-2 and mPGES-1-dependent PGE(2) production in pulmonary
      epithelial cells. Legionella induced the release of PGE(2) in primary human small
      airway epithelial cells and A549 cells. This was accompanied by an increased
      expression of COX-2 and mPGES-1 as well as an increased PLA(2) activity in
      infected cells. Deletion of the type IV secretion system Dot/Icm did not impair
      Legionella-related COX-2 expression or PGE(2) release in A549 cells. L.
      pneumophila induced the degradation of IkappaBalpha and activated NF-kappaB.
      Inhibition of IKK blocked L. pneumophila-induced PGE(2) release and COX-2
      expression. We noted activation of p38 and p42/44 MAP kinase in Legionella
      infected A549 cells. Moreover, membrane translocation and activation of PKCalpha
      was observed in infected cells. PKCalpha and p38 and p42/44 MAP kinase inhibitors
      reduced PGE(2) release and COX-2 expression. In summary, PKCalpha and p38 and
      p42/44 MAP kinase controlled COX-2 expression and subsequent PGE(2) release by
      Legionella-infected lung epithelial cells. These pathways may significantly
      contribute to the host response in Legionnaires' disease.

PMID- 17012372
TI  - Moxifloxacin but not ciprofloxacin or azithromycin selectively inhibits IL-8, IL
      6, ERK1/2, JNK, and NF-kappaB activation in a cystic fibrosis epithelial cell
      line.
AB  - Cystic fibrosis (CF) is associated with severe neutrophilic airway inflammation.
      We showed that moxifloxacin (MXF) inhibits IL-8 and MAPK activation in monocytic
      and respiratory epithelial cells. Azithromycin (AZM) and ciprofloxacin (CIP) are
      used clinically in CF. Thus we now examined effects of MXF, CIP, and AZM directly
      on CF cells. IB3, a CF bronchial cell line, and corrected C38 cells were treated
      with TNF-alpha, IL-1beta, or LPS with or without 5-50 microg/ml MXF, CIP, or AZM.
      IL-6 and IL-8 secretion (ELISA), MAPKs ERK1/2, JNK, p38, and p65 NF-kappaB
      (Western blot) activation were measured. Baseline IL-6 was sixfold higher in IB3
      than C38 cells but IL-8 was similar. TNF-alpha and IL-1beta increased IL-6 and IL
      8 12- to 67-fold with higher levels in IB3 than C38 cells post-TNF-alpha (P <
      0.05). Levels were unchanged following LPS. Baseline phosphorylated form of
      ERK1/2 (p-ERK1/2), JNK, and NF-kappaB p65 were higher in IB3 than C38 cells (5-,
      1.4-, and 1.4-fold), and following TNF-alpha increased, as did the p-p38, by 1.6-
      to 2-fold. MXF (5-50 microg/ml) and CIP (50 microg/ml), but not AZM, suppressed
      IL-6 and IL-8 secretion by up to 69%. MXF inhibited TNF-alpha-stimulated MAPKs
      ERK1/2, 46-kDa JNK, and NF-kappaB up to 60%, 40%, and 40%, respectively. In
      contrast, MXF did not inhibit p38 activation, implying a highly selective
      pretranslational effect. In conclusion, TNF-alpha and IL-1beta induce an
      exaggerated inflammatory response in CF airway cells, inhibited by MXF more than
      by CIP or AZM. Clinical trials are recommended to assess efficacy in CF and other
      chronic lung diseases.

PMID- 17012373
TI  - Vector competence of Glossina palpalis gambiensis for Trypanosoma brucei s.l. and
      genetic diversity of the symbiont Sodalis glossinidius.
AB  - Tsetse flies transmit African trypanosomes, responsible for sleeping sickness in
      humans and nagana in animals. This disease affects many people with considerable
      impact on public health and economy in sub-Saharan Africa, whereas trypanosomes'
      resistance to drugs is rising. The symbiont Sodalis glossinidius is considered to
      play a role in the ability of the fly to acquire trypanosomes. Different species
      of Glossina were shown to harbor genetically distinct populations of S.
      glossinidius. We therefore investigated whether vector competence for a given
      trypanosome species could be linked to the presence of specific genotypes of S.
      glossinidius. Glossina palpalis gambiensis individuals were fed on blood infected
      either with Trypanosoma brucei gambiense or Trypanosoma brucei brucei. The
      genetic diversity of S. glossinidius strains isolated from infected and
      noninfected dissected flies was investigated using amplified fragment length
      polymorphism markers. Correspondence between occurrence of these markers and
      parasite establishment was analyzed using multivariate analysis. Sodalis
      glossinidius strains isolated from T. brucei gambiense-infected flies clustered
      differently than that isolated from T. brucei brucei-infected individuals. The
      ability of T. brucei gambiense and T. brucei brucei to establish in G. palpalis
      gambiensis insect midgut is statistically linked to the presence of specific
      genotypes of S. glossinidius. This could explain variations in Glossina vector
      competence in the wild. Then, assessment of the prevalence of specific S.
      glossinidius genotypes could lead to novel risk management strategies.

PMID- 17012374
TI  - Lack of resolution in the animal phylogeny: closely spaced cladogeneses or
      undetected systematic errors?
AB  - A recent phylogenomic study reported that the animal phylogeny was unresolved
      despite the use of 50 genes. This lack of resolution was interpreted as "a
      positive signature of closely spaced cladogenetic events." Here, we propose that
      this lack of resolution is rather due to the mutual cancellation of the
      phylogenetic signal (historical) and the nonphylogenetic signal (due to
      systematic errors) that results from inadequate taxon sampling and/or model of
      sequence evolution. Starting with a data set of comparable size, we use 3
      different strategies to reduce the nonphylogenetic signal: 1) increasing the
      number of species; 2) replacing a fast-evolving species by a slowly evolving one;
      and 3) using a better model of sequence evolution. In all cases, the phylogenetic
      resolution is markedly improved, in agreement with our hypothesis that the
      originally reported lack of resolution was artifactual.

PMID- 17012375
TI  - Activation of area MT/V5 and the right inferior parietal cortex during the
      discrimination of transient direction changes in translational motion.
AB  - The perception of changes in the direction of objects that translate in space is
      an important function of our visual system. Here we investigate the brain
      electrical phenomena underlying such a function by using a combination of
      magnetoencephalography (MEG) and magnetic resonance imaging. We recorded MEG
      evoked responses in 9 healthy human subjects while they discriminated the
      direction of a transient change in a translationally moving random dot pattern
      presented either to the right or to the left of a central fixation point. We
      found that responses reached their maximum in 2 main regions corresponding to
      motion processing area middle temporal (MT)/V5 contralateral to the stimulated
      visual field, and to the right inferior parietal lobe (rIPL). The activation
      latencies were very similar in both regions ( approximately 135 ms) following the
      direction change onset. Our findings suggest that area MT/V5 provides the
      strongest sensory signal in response to changes in the direction of translational
      motion, whereas area rIPL may be involved either in the sensory processing of
      transient motion signals or in the processing of signals related to orienting of
      attention.

PMID- 17012376
TI  - The Association between handedness, brain asymmetries, and corpus callosum size
      in chimpanzees (Pan troglodytes).
AB  - It has been suggested from studies in human subjects that sex, handedness, and
      brain asymmetries influence variation in corpus callosum (CC) size and these
      differences reflect the degree of connectivity between homotopic regions of the
      left and right cerebral hemispheres. Here we report that handedness is associated
      with variation in the size of the CC in chimpanzees. We further report that
      variation in brain asymmetries in a cortical region homologous to Broca's area is
      associated with the size of the CC but differs for right- and left-handed
      individuals. Collectively, the results suggest that individual differences in
      functional and neuroanatomical asymmetries are associated with CC variation not
      just in humans but also in chimpanzees and therefore may reflect a common neural
      basis for laterality in these 2 species.

PMID- 17012377
TI  - Handedness is associated with asymmetries in gyrification of the cerebral cortex
      of chimpanzees.
AB  - Gyrification of the cerebral cortex reflects complexity in cortical folding
      during development of the brain. In this paper, we evaluated whether chimpanzees
      show asymmetries in gyrification and if variation in gyrification asymmetries
      were associated with handedness. Magnetic resonance images were obtained in a
      sample of 76 chimpanzees, and gyrification measures were obtained from 10 equally
      spaced slices of the cortex. Asymmetry quotients (AQs) in gyrification were
      compared for 4 measures of handedness including reaching, coordinated bimanual
      actions, manual gestures, and throwing. Overall, the chimpanzees showed
      significant differences between the right and left hemispheres that were region
      specific. Significant differences in AQ's were found in right- and nonright
      handed chimpanzees for throwing and, to a lesser degree, for manual gestures.
      Increasing age was associated with increasing gyrification in the prefrontal
      regions, particularly in female chimpanzees. The results indicate that variation
      in gyrification between hemispheres is associated with functional measures of
      laterality in chimpanzees.

PMID- 17012378
TI  - The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans
      germ line.
AB  - mRNA regulation is crucial for many aspects of metazoan development and
      physiology, including regulation of stem cells and synaptic plasticity. In the
      nematode germ line, RNA regulators control stem cell maintenance, the
      sperm/oocyte decision, and progression through meiosis. Of particular importance
      to this work are three GLD (germ-line development) regulatory proteins, each of
      which promotes entry into the meiotic cell cycle: GLD-1 is a STAR/Quaking
      translational repressor, GLD-2 is a cytoplasmic poly(A) polymerase, and GLD-3 is
      a homolog of Bicaudal-C. Here we report that the gld-1 mRNA is a direct target of
      the GLD-2 poly(A) polymerase: polyadenylation of gld-1 mRNA depends on GLD-2, the
      abundance of GLD-1 protein is dependent on GLD-2, and the gld-1 mRNA
      coimmunoprecipitates with both GLD-2 and GLD-3 proteins. We suggest that the GLD
      2 poly(A) polymerase enhances entry into the meiotic cell cycle at least in part
      by activating GLD-1 expression. The importance of this conclusion is twofold.
      First, the activation of gld-1 mRNA by GLD-2 identifies a positive regulatory
      step that reinforces the decision to enter the meiotic cell cycle. Second, gld-1
      mRNA is initially repressed by FBF (for fem-3 binding factor) to maintain stem
      cells but then becomes activated by the GLD-2 poly(A) polymerase once stem cells
      begin to make the transition into the meiotic cell cycle. Therefore, a molecular
      switch regulates gld-1 mRNA activity to accomplish the transition from mitosis to
      meiosis.

PMID- 17012379
TI  - Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron
      oxygenase with a key role in inositol metabolism.
AB  - Altered metabolism of the inositol sugars myo-inositol (MI) and d-chiro-inositol
      is implicated in diabetic complications. In animals, catabolism of MI and D-chiro
      inositol depends on the enzyme MI oxygenase (MIOX), which catalyzes the first
      committed step of the glucuronate-xylulose pathway, and is found almost
      exclusively in the kidneys. The crystal structure of MIOX, in complex with MI,
      has been determined by multiwavelength anomalous diffraction methods and refined
      at 2.0-A resolution (R=0.206, Rfree=0.253). The structure reveals a monomeric,
      single-domain protein with a mostly helical fold that is distantly related to the
      diverse HD domain superfamily. Five helices form the structural core and provide
      six ligands (four His and two Asp) for the di-iron center, in which the two iron
      atoms are bridged by a putative hydroxide ion and one of the Asp ligands, Asp
      124. A key loop forms a lid over the MI substrate, which is coordinated in
      bidentate mode to one iron atom. It is proposed that this mode of iron
      coordination, and interaction with a key Lys residue, activate MI for bond
      cleavage. The structure also reveals the basis of substrate specificity and
      suggests routes for the development of specific MIOX inhibitors.

PMID- 17012380
TI  - Escherichia coli RNA polymerase recognition of a sigma70-dependent promoter
      requiring a -35 DNA element and an extended -10 TGn motif.
AB  - Escherichia coli sigma70-dependent promoters have typically been characterized as
      either -10/-35 promoters, which have good matches to both the canonical -10 and
      the -35 sequences or as extended -10 promoters (TGn/-10 promoters), which have
      the TGn motif and an excellent match to the -10 consensus sequence. We report
      here an investigation of a promoter, P(minor), that has a nearly perfect match to
      the -35 sequence and has the TGn motif. However, P(minor) contains an extremely
      poor sigma70 -10 element. We demonstrate that P(minor) is active both in vivo and
      in vitro and that mutations in either the -35 or the TGn motif eliminate its
      activity. Mutation of the TGn motif can be compensated for by mutations that make
      the -10 element more canonical, thus converting the -35/TGn promoter to a -35/-10
      promoter. Potassium permanganate footprinting on the nontemplate and template
      strands indicates that when polymerase is in a stable (open) complex with
      P(minor), the DNA is single stranded from positions -11 to +4. We also
      demonstrate that transcription from P(minor) incorporates nontemplated
      ribonucleoside triphosphates at the 5' end of the P(minor) transcript, which
      results in an anomalous assignment for the start site when primer extension
      analysis is used. P(minor) represents one of the few -35/TGn promoters that have
      been characterized and serves as a model for investigating functional differences
      between these promoters and the better-characterized -10/-35 and extended -10
      promoters used by E. coli RNA polymerase.

PMID- 17012381
TI  - Comparative genetics of the rdar morphotype in Salmonella.
AB  - The Salmonella rdar morphotype is a distinct, rough and dry colony morphology
      formed by the extracellular interaction of thin aggregative fimbriae (Tafi or
      curli), cellulose, and other polysaccharides. Cells in rdar colonies are more
      resistant to desiccation and exogenous stresses, which is hypothesized to aid in
      the passage of pathogenic Salmonella spp. between hosts. Here we analyzed the
      genetic and phenotypic conservation of the rdar morphotype throughout the entire
      Salmonella genus. The rdar morphotype was conserved in 90% of 80 isolates
      representing all 7 Salmonella groups; however, the frequency was only 31% in a
      reference set of 16 strains (Salmonella reference collection C [SARC]).
      Comparative gene expression analysis was used to separate cis- and trans-acting
      effects on promoter activity for the 16 SARC strains, focusing on the 780-bp
      intergenic region containing divergent promoters for the master regulator of the
      rdar morphotype (agfD) and the Tafi structural genes (agfB). Surprisingly,
      promoter functionality was conserved in most isolates, and loss of the phenotype
      was due primarily to defects in trans-acting regulatory factors. We hypothesize
      that trans differences have been caused by domestication, whereas cis
      differences, detected for Salmonella enterica subsp. arizonae isolates, may
      reflect an evolutionary change in lifestyle. Our results demonstrate that the
      rdar morphotype is conserved throughout the salmonellae, but they also emphasize
      that regulation is an important source of variability among isolates.

PMID- 17012382
TI  - Mutational analysis to define an activating region on the redox-sensitive
      transcriptional regulator OxyR.
AB  - The OxyR transcription factor is a key regulator of the Escherichia coli response
      to oxidative stress. Previous studies showed that OxyR binding to a target
      promoter enhances RNA polymerase binding and vice versa, suggesting a direct
      interaction between OxyR and RNA polymerase. To identify the region of OxyR that
      might contact RNA polymerase, we carried out alanine scanning and random
      mutagenesis of oxyR. The combination of these approaches led to the
      identification of several mutants defective in the activation of an OxyR target
      gene. A subset of the mutations map to the DNA-binding domain, other mutations
      appear to affect dimerization of the regulatory domain, while another group is
      suggested to affect disulfide bond formation. The two mutations, D142A and R273H,
      giving the most dramatic phenotype are located in a patch on the surface of the
      oxidized OxyR protein and possibly define an activating region on OxyR.

PMID- 17012383
TI  - Release of immunity protein requires functional endonuclease colicin import
      machinery.
AB  - Bacteria producing endonuclease colicins are protected against the cytotoxic
      activity by a small immunity protein that binds with high affinity and
      specificity to inactivate the endonuclease. This complex is released into the
      extracellular medium, and the immunity protein is jettisoned upon binding of the
      complex to susceptible cells. However, it is not known how and at what stage
      during infection the immunity protein release occurs. Here, we constructed a
      hybrid immunity protein composed of the enhanced green fluorescent protein (EGFP)
      fused to the colicin E2 immunity protein (Im2) to enhance its detection. The EGFP
      Im2 protein binds the free colicin E2 with a 1:1 stoichiometry and specifically
      inhibits its DNase activity. The addition of this hybrid complex to susceptible
      cells reveals that the release of the hybrid immunity protein is a time-dependent
      process. This process is achieved 20 min after the addition of the complex to the
      cells. We showed that complex dissociation requires a functional translocon
      formed by the BtuB protein and one porin (either OmpF or OmpC) and a functional
      import machinery formed by the Tol proteins. Cell fractionation and protease
      susceptibility experiments indicate that the immunity protein does not cross the
      cell envelope during colicin import. These observations suggest that dissociation
      of the immunity protein occurs at the outer membrane surface and requires full
      translocation of the colicin E2 N-terminal domain.

PMID- 17012384
TI  - The plasminogen-binding group A streptococcal M protein-related protein Prp binds
      plasminogen via arginine and histidine residues.
AB  - The migration of the human pathogen Streptococcus pyogenes (group A
      streptococcus) from localized to deep tissue sites may result in severe invasive
      disease, and sequestration of the host zymogen plasminogen appears crucial for
      virulence. Here, we describe a novel plasminogen-binding M protein, the
      plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp).
      Prp is phylogenetically distinct from previously described plasminogen-binding M
      proteins of group A, C, and G streptococci. While competition experiments
      indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective
      concentration = 0.34 microM), Prp nonetheless binds plasminogen with high
      affinity and at physiologically relevant concentrations of plasminogen (K(d) =
      7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site
      indicates that unlike the majority of plasminogen receptors, Prp does not
      interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine
      of lysine residues Lys(96) and Lys(101) reduced but did not abrogate plasminogen
      binding by Prp. Plasminogen binding was abolished only with the additional
      mutagenesis of Arg(107) and His(108) to alanine. Furthermore, mutagenesis of
      Arg(107) and His(108) abolished plasminogen binding by Prp despite the presence
      of Lys(96) and Lys(101) in the binding site. Thus, binding to plasminogen via
      arginine and histidine residues appears to be a conserved mechanism among
      plasminogen-binding M proteins.

PMID- 17012385
TI  - Iron starvation triggers the stringent response and induces amino acid
      biosynthesis for bacillibactin production in Bacillus subtilis.
AB  - Iron deprivation in bacteria causes the derepression of genes controlled by the
      ferric uptake regulator (Fur). The present microarray analysis of iron-starved
      Bacillus subtilis cells grown in minimal medium unveils additional physiological
      effects on a large number of genes linked to stringent-response regulation and to
      genes involved in amino acid biosynthesis associated with pathways essential for
      bacillibactin production.

PMID- 17012386
TI  - Wall teichoic acid polymers are dispensable for cell viability in Bacillus
      subtilis.
AB  - An extensive literature has established that the synthesis of wall teichoic acid
      in Bacillus subtilis is essential for cell viability. Paradoxically, we have
      recently shown that wall teichoic acid biogenesis is dispensable in
      Staphylococcus aureus (M. A. D'Elia, M. P. Pereira, Y. S. Chung, W. Zhao, A.
      Chau, T. J. Kenney, M. C. Sulavik, T. A. Black, and E. D. Brown, J. Bacteriol.
      188:4183-4189, 2006). A complex pattern of teichoic acid gene dispensability was
      seen in S. aureus where the first gene (tarO) was dispensable and later acting
      genes showed an indispensable phenotype. Here we show, for the first time, that
      wall teichoic acid synthesis is also dispensable in B. subtilis and that a
      similar gene dispensability pattern is seen where later acting enzymes display an
      essential phenotype, while the gene tagO, whose product catalyzes the first step
      in the pathway, could be deleted to yield viable mutants devoid of teichoic acid
      in the cell wall.

PMID- 17012387
TI  - Role of streptococcal T antigens in superficial skin infection.
AB  - FCT region genes of Streptococcus pyogenes encode surface proteins that include
      fibronectin- and collagen-binding proteins and the serological markers known as T
      antigens, some of which give rise to pilus-like appendages. It remains to be
      established whether FCT region surface proteins contribute to virulence by in
      vivo models of infection. In this study, a highly sensitive and ecologically
      relevant humanized mouse model was used to measure superficial skin infection.
      Three genes encoding FCT region surface proteins essential for T-serotype
      specificity were inactivated. Both the Deltacpa and DeltaprtF2 mutants were
      highly attenuated for virulence when topically applied to the skin following
      exponential growth but were fully virulent when delivered in stationary phase. In
      contrast, the DeltafctA mutant was virulent at the skin, regardless of its
      initial growth state. Immunoblots of cell extracts revealed anti-FctA-reactive,
      ladder-like polymers characteristic of streptococcal pili. In addition, FctA
      formed a heteropolymer with the putative collagen-binding protein Cpa. The
      DeltafctA mutant showed a loss in anti-Cpa-reactive polymers, whereas anti-FctA
      reactive polymers were reduced in the Deltacpa mutant. The findings suggest that
      both FctA and Cpa are required for pilus formation, but importantly, an intact
      pilus is not essential for Cpa-mediated virulence. Although it is an integral
      part of the T-antigen complex, the fibronectin-binding protein PrtF2 is not
      covalently linked to the FctA- and Cpa-containing heteropolymer derived from cell
      extracts. The data provide direct evidence that streptococcal T antigens function
      as virulence factors in vivo, but they also reveal that a pilus-like structure is
      not essential for the most common form of streptococcal skin disease.

PMID- 17012388
TI  - The algT gene of Pseudomonas syringae pv. glycinea and new insights into the
      transcriptional organization of the algT-muc gene cluster.
AB  - The phytopathogenic bacterium Pseudomonas syringae pv. glycinea infects soybean
      plants and causes bacterial blight. In addition to P. syringae, the human
      pathogen Pseudomonas aeruginosa and the soil bacterium Azotobacter vinelandii
      produce the exopolysaccharide alginate, a copolymer of d-mannuronic and l
      guluronic acids. Alginate production in P. syringae has been associated with
      increased fitness and virulence in planta. Alginate biosynthesis is tightly
      controlled by proteins encoded by the algT-muc regulatory gene cluster in P.
      aeruginosa and A. vinelandii. These genes encode the alternative sigma factor
      AlgT (sigma(22)), its anti-sigma factors MucA and MucB, MucC, a protein with a
      controversial function that is absent in P. syringae, and MucD, a periplasmic
      serine protease and homolog of HtrA in Escherichia coli. We compared an alginate
      deficient algT mutant of P. syringae pv. glycinea with an alginate-producing
      derivative in which algT is intact. The alginate-producing derivative grew
      significantly slower in vitro growth but showed increased epiphytic fitness and
      better symptom development in planta. Evaluation of expression levels for algT,
      mucA, mucB, mucD, and algD, which encodes an alginate biosynthesis gene, showed
      that mucD transcription is not dependent on AlgT in P. syringae in vitro.
      Promoter mapping using primer extension experiments confirmed this finding.
      Results of reverse transcription-PCR demonstrated that algT, mucA, and mucB are
      cotranscribed as an operon in P. syringae. Northern blot analysis revealed that
      mucD was expressed as a 1.75-kb monocistronic mRNA in P. syringae.

PMID- 17012389
TI  - SarA is a repressor of hla (alpha-hemolysin) transcription in Staphylococcus
      aureus: its apparent role as an activator of hla in the prototype strain NCTC
      8325 depends on reduced expression of sarS.
AB  - In most Staphylococcus aureus strains, inactivation of sarA increases hla
      transcription, indicating that sarA is a repressor. However, in S. aureus NCTC
      8325 and its derivatives, used for most studies of hla regulation, inactivation
      of sarA resulted in decreased hla transcription. The disparate phenotype of
      strain NCTC 8325 seems to be associated with its rsbU mutation, which leads to
      sigma(B) deficiency. This has now been verified by the demonstration that sarA
      repressed hla transcription in an rsbU+ derivative of strain 8325-4 (SH1000).
      That sarA could act as a repressor of hla in an 8325-4 background was confirmed
      by the observation that inactivation of sarA in an agr sarS rot triple mutant
      dramatically increased hla transcription to wild-type levels. However, the
      apparent role of sarA as an activator of hla in 8325-4 was not a result of the
      rsbU mutation alone, as inactivation of sarA in another rsbU mutant, strain V8,
      led to increased hla transcription. Northern blot analysis revealed much higher
      levels of sarS mRNA in strain V8 than in 8325-4, which was likely due to the
      mutation in the sarS activator, tcaR, in 8325-4, which was not found in strain
      V8. On the other hand, the relative increase in sarS transcription upon the
      inactivation of sarA was 15-fold higher in 8325-4 than in strain V8. Because of
      this, inactivation of sarA in 8325-4 means a net increase in repressor activity,
      whereas in strain V8, inactivation of sarA means a net decrease in repressor
      activity and, therefore, enhanced hla transcription.

PMID- 17012390
TI  - Effect of site-specific mutations in different phosphotransfer domains of the
      chemosensory protein ChpA on Pseudomonas aeruginosa motility.
AB  - The virulence of Pseudomonas aeruginosa and other surface pathogens involves the
      coordinate expression of a wide range of virulence determinants, including type
      IV pili. These surface filaments are important for the colonization of host
      epithelial tissues and mediate bacterial attachment to, and translocation across,
      surfaces by a process known as twitching motility. This process is controlled in
      part by a complex signal transduction system whose central component, ChpA,
      possesses nine potential sites of phosphorylation, including six histidine
      containing phosphotransfer (HPt) domains, one serine-containing phosphotransfer
      domain, one threonine-containing phosphotransfer domain, and one CheY-like
      receiver domain. Here, using site-directed mutagenesis, we show that normal
      twitching motility is entirely dependent on the CheY-like receiver domain and
      partially dependent on two of the HPt domains. Moreover, under different assay
      conditions, point mutations in several of the phosphotransfer domains of ChpA
      give rise to unusual "swarming" phenotypes, possibly reflecting more subtle
      perturbations in the control of P. aeruginosa motility that are not evident from
      the conventional twitching stab assay. Together, these results suggest that ChpA
      plays a central role in the complex regulation of type IV pilus-mediated motility
      in P. aeruginosa.

PMID- 17012391
TI  - The Seventh International Conference on the Genetics of Streptococci, Lactococci,
      and Enterococci.

PMID- 17012392
TI  - Identification of a nisI promoter within the nisABCTIP operon that may enable
      establishment of nisin immunity prior to induction of the operon via signal
      transduction.
AB  - Certain strains of Lactococcus lactis produce the broad-spectrum bacteriocin
      nisin, which belongs to the lantibiotic class of antimicrobial peptides. The
      genes encoding nisin are organized in three contiguous operons: nisABTCIP,
      encoding production and immunity (nisI); nisRK, encoding regulation; and nisFEG,
      also involved in immunity. Transcription of nisABTCIP and nisFEG requires
      autoinduction by external nisin via signal transducing by NisRK. This
      organization poses the intriguing question of how sufficient immunity (NisI) can
      be expressed when the nisin cluster enters a new cell, before it encounters
      external nisin. In this study, Northern analysis in both Lactococcus and
      Enterococcus backgrounds revealed that nisI mRNA was present under conditions
      when no nisA transcription was occurring, suggesting an internal promoter within
      the operon. The nisA transcript was significantly more stable than nisI, further
      substantiating this. Reverse transcriptase PCR analysis revealed that the
      transcription initiated just upstream from nisI. Fusing this region to a lacZ
      gene in a promoter probe vector demonstrated that a promoter was present. The
      transcription start site (TSS) of the nisI promoter was mapped at bp 123 upstream
      of the nisI translation start codon. Ordered 5' deletions revealed that
      transcription activation depended on sequences located up to bp -234 from the
      TSS. The presence of poly(A) tracts and computerized predictions for this region
      suggested that a high degree of curvature may be required for transcription
      initiation. The existence of this nisI promoter is likely an evolutionary
      adaptation of the nisin gene cluster to enable its successful establishment in
      other cells following horizontal transfer.

PMID- 17012393
TI  - Complete genome of acute rheumatic fever-associated serotype M5 Streptococcus
      pyogenes strain manfredo.
AB  - Comparisons of the 1.84-Mb genome of serotype M5 Streptococcus pyogenes strain
      Manfredo with previously sequenced genomes emphasized the role of prophages in
      diversification of S. pyogenes and the close relationship between strain Manfredo
      and MGAS8232, another acute rheumatic fever-associated strain.

PMID- 17012395
TI  - Competence-dependent bacteriocin production by Streptococcus gordonii DL1
      (Challis).
AB  - The production of streptocins STH(1) and STH(2) by Streptococcus gordonii DL1
      (Challis) is directly controlled by the competence regulon, which requires intact
      comR and comAB loci. The streptocin (sth) locus comprises two functional genes,
      sthA and sthB. Whereas STH(1) activity requires sthA alone, STH(2) activity
      depends on both genes.

PMID- 17012394
TI  - Experimental and computational assessment of conditionally essential genes in
      Escherichia coli.
AB  - Genome-wide gene essentiality data sets are becoming available for Escherichia
      coli, but these data sets have yet to be analyzed in the context of a genome
      scale model. Here, we present an integrative model-driven analysis of the Keio E.
      coli mutant collection screened in this study on glycerol-supplemented minimal
      medium. Out of 3,888 single-deletion mutants tested, 119 mutants were unable to
      grow on glycerol minimal medium. These conditionally essential genes were then
      evaluated using a genome scale metabolic and transcriptional-regulatory model of
      E. coli, and it was found that the model made the correct prediction in
      approximately 91% of the cases. The discrepancies between model predictions and
      experimental results were analyzed in detail to indicate where model improvements
      could be made or where the current literature lacks an explanation for the
      observed phenotypes. The identified set of essential genes and their model-based
      analysis indicates that our current understanding of the roles these essential
      genes play is relatively clear and complete. Furthermore, by analyzing the data
      set in terms of metabolic subsystems across multiple genomes, we can project
      which metabolic pathways are likely to play equally important roles in other
      organisms. Overall, this work establishes a paradigm that will drive model
      enhancement while simultaneously generating hypotheses that will ultimately lead
      to a better understanding of the organism.

PMID- 17012396
TI  - Characterization of the carboxysomal carbonic anhydrase CsoSCA from
      Halothiobacillus neapolitanus.
AB  - In cyanobacteria and many chemolithotrophic bacteria, the CO(2)-fixing enzyme
      ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) is sequestered into
      polyhedral protein bodies called carboxysomes. The carboxysome is believed to
      function as a microcompartment that enhances the catalytic efficacy of RubisCO by
      providing the enzyme with its substrate, CO(2), through the action of the shell
      protein CsoSCA, which is a novel carbonic anhydrase. In the work reported here,
      the biochemical properties of purified, recombinant CsoSCA were studied, and the
      catalytic characteristics of the carbonic anhydrase for the CO(2) hydration and
      bicarbonate dehydration reactions were compared with those of intact and ruptured
      carboxysomes. The low apparent catalytic rates measured for CsoSCA in intact
      carboxysomes suggest that the protein shell acts as a barrier for the CO(2) that
      has been produced by CsoSCA through directional dehydration of cytoplasmic
      bicarbonate. This CO(2) trap provides the sequestered RubisCO with ample
      substrate for efficient fixation and constitutes a means by which
      microcompartmentalization enhances the catalytic efficiency of this enzyme.

PMID- 17012397
TI  - The ColRS two-component system regulates membrane functions and protects
      Pseudomonas putida against phenol.
AB  - As reported, the two-component system ColRS is involved in two completely
      different processes. It facilitates the root colonization ability of Pseudomonas
      fluorescens and is necessary for the Tn4652 transposition-dependent accumulation
      of phenol-utilizing mutants in Pseudomonas putida. To determine the role of the
      ColRS system in P. putida, we searched for target genes of response regulator
      ColR by use of a promoter library. Promoter screening was performed on phenol
      plates to mimic the conditions under which the effect of ColR on transposition
      was detected. The library screen revealed the porin-encoding gene oprQ and the
      alginate biosynthesis gene algD occurring under negative control of ColR. Binding
      of ColR to the promoter regions of oprQ and algD in vitro confirmed its direct
      involvement in regulation of these genes. Additionally, the porin-encoding gene
      ompA(PP0773) and the type I pilus gene csuB were also identified in the promoter
      screen. However, it turned out that ompA(PP0773) and csuB were actually affected
      by phenol and that the influence of ColR on these promoters was indirect. Namely,
      our results show that ColR is involved in phenol tolerance of P. putida. Phenol
      MIC measurement demonstrated that a colR mutant strain did not tolerate elevated
      phenol concentrations. Our data suggest that increased phenol susceptibility is
      also the reason for inhibition of transposition of Tn4652 in phenol-starving colR
      mutant bacteria. Thus, the current study revealed the role of the ColRS two
      component system in regulation of membrane functionality, particularly in phenol
      tolerance of P. putida.

PMID- 17012398
TI  - Agrobacterium rhizogenes GALLS protein contains domains for ATP binding, nuclear
      localization, and type IV secretion.
AB  - Agrobacterium tumefaciens and Agrobacterium rhizogenes are closely related plant
      pathogens that cause different diseases, crown gall and hairy root. Both diseases
      result from transfer, integration, and expression of plasmid-encoded bacterial
      genes located on the transferred DNA (T-DNA) in the plant genome. Bacterial
      virulence (Vir) proteins necessary for infection are also translocated into plant
      cells. Transfer of single-stranded DNA (ssDNA) and Vir proteins requires a type
      IV secretion system, a protein complex spanning the bacterial envelope. A.
      tumefaciens translocates the ssDNA-binding protein VirE2 into plant cells, where
      it binds single-stranded T-DNA and helps target it to the nucleus. Although some
      strains of A. rhizogenes lack VirE2, they are pathogenic and transfer T-DNA
      efficiently. Instead, these bacteria express the GALLS protein, which is
      essential for their virulence. The GALLS protein can complement an A. tumefaciens
      virE2 mutant for tumor formation, indicating that GALLS can substitute for VirE2.
      Unlike VirE2, GALLS contains ATP-binding and helicase motifs similar to those in
      TraA, a strand transferase involved in conjugation. Both GALLS and VirE2 contain
      nuclear localization sequences and a C-terminal type IV secretion signal. Here we
      show that mutations in any of these domains abolished the ability of GALLS to
      substitute for VirE2.

PMID- 17012399
TI  - Lysine decarboxylase expression by Vibrio vulnificus is induced by SoxR in
      response to superoxide stress.
AB  - Lysine decarboxylase expression by Vibrio vulnificus, which is up-regulated by
      CadC in response to acid stress, is also induced by SoxR in response to
      superoxide stress. SoxR binds to the promoter region of the cadBA operon, coding
      for a lysine-cadaverine antiporter (CadB) and a lysine decarboxylase (CadA). The
      induction of cadBA transcription by SoxR is independent of CadC. Cadaverine,
      which neutralizes the external medium, also appears to scavenge superoxide
      radicals, since increasing cellular cadaverine by elevating the gene dosage of
      cadBA significantly diminished the induction of Mn-containing superoxide
      dismutase under methyl viologen-induced oxidative stress. Consistently, a lack of
      cadaverine caused by mutation in cadA resulted in low tolerance to oxidative
      stress compared with that of the wild type.

PMID- 17012400
TI  - Abortive phage resistance mechanism AbiZ speeds the lysis clock to cause
      premature lysis of phage-infected Lactococcus lactis.
AB  - The conjugative plasmid pTR2030 has been used extensively to confer phage
      resistance in commercial Lactococcus starter cultures. The plasmid harbors a 16
      kb region, flanked by insertion sequence (IS) elements, that encodes the
      restriction/modification system LlaI and carries an abortive infection gene,
      abiA. The AbiA system inhibits both prolate and small isometric phages by
      interfering with the early stages of phage DNA replication. However, abiA alone
      does not account for the full abortive activity reported for pTR2030. In this
      study, a 7.5-kb region positioned within the IS elements and downstream of abiA
      was sequenced to reveal seven additional open reading frames (ORFs). A single
      ORF, designated abiZ, was found to be responsible for a significant reduction in
      plaque size and an efficiency of plaquing (EOP) of 10(-6), without affecting
      phage adsorption. AbiZ causes phage phi31-infected Lactococcus lactis NCK203 to
      lyse 15 min early, reducing the burst size of phi31 100-fold. Thirteen of 14
      phages of the P335 group were sensitive to AbiZ, through reduction in either
      plaque size, EOP, or both. The predicted AbiZ protein contains two predicted
      transmembrane helices but shows no significant DNA homologies. When the phage
      phi31 lysin and holin genes were cloned into the nisin-inducible shuttle vector
      pMSP3545, nisin induction of holin and lysin caused partial lysis of NCK203. In
      the presence of AbiZ, lysis occurred 30 min earlier. In holin-induced cells,
      membrane permeability as measured using propidium iodide was greater in the
      presence of AbiZ. These results suggest that AbiZ may interact cooperatively with
      holin to cause premature lysis.

PMID- 17012401
TI  - Surface protein IsdC and Sortase B are required for heme-iron scavenging of
      Bacillus anthracis.
AB  - Bacillus anthracis, the spore-forming agent of anthrax, requires iron for growth
      and is capable of scavenging heme-iron during infection. We show here that the B.
      anthracis iron-regulated surface determinants (isd) locus encompasses isdC,
      specifying a heme-iron binding surface protein. Anchoring of IsdC to the cell
      wall envelopes of vegetative bacilli requires srtB, which encodes sortase B.
      Purified sortase B cleaves IsdC between the threonine and the glycine of its
      NPKTG motif sorting signal. B. anthracis variants lacking either isdC or srtB
      display defects in heme-iron scavenging, suggesting that IsdC binding to heme
      iron in the cell wall envelope contributes to bacterial uptake of heme.

PMID- 17012402
TI  - Contribution of ethylene biosynthesis for resistance to blast fungus infection in
      young rice plants.
AB  - The role of ethylene (ET) in resistance to infection with blast fungus
      (Magnaporthe grisea) in rice (Oryza sativa) is poorly understood. To study it, we
      quantified ET levels after inoculation, using young rice plants at the four-leaf
      stage of rice cv Nipponbare (wild type) and its isogenic plant (IL7), which
      contains the Pi-i resistance gene to blast fungus race 003. Small necrotic
      lesions by hypersensitive reaction (HR) were formed at 42 to 72 h postinoculation
      (hpi) in resistant IL7 leaves, and whitish expanding lesions at 96 hpi in
      susceptible wild-type leaves. Notable was the enhanced ET emission at 48 hpi
      accompanied by increased 1-aminocyclopropane-1-carboxylic acid (ACC) levels and
      highly elevated ACC oxidase (ACO) activity in IL7 leaves, whereas only an
      enhanced ACC increase at 96 hpi in wild-type leaves. Among six ACC synthase (ACS)
      and seven ACO genes found in the rice genome, OsACS2 was transiently expressed at
      48 hpi in IL7 and at 96 hpi in wild type, and OsACO7 was expressed at 48 hpi in
      IL7. Treatment with an inhibitor for ACS, aminooxyacetic acid, suppressed
      enhanced ET emission at 48 hpi in IL7, resulting in expanding lesions instead of
      HR lesions. Exogenously supplied ACC compromised the aminooxyacetic acid-induced
      breakdown of resistance in IL7, and treatment with 1-methylcyclopropene and
      silver thiosulfate, inhibitors of ET action, did not suppress resistance. These
      findings suggest the importance of ET biosynthesis and, consequently, the
      coproduct, cyanide, for HR-accompanied resistance to blast fungus in young rice
      plants and the contribution of induced OsACS2 and OsACO7 gene expression to it.

PMID- 17012403
TI  - Calcium entry mediated by GLR3.3, an Arabidopsis glutamate receptor with a broad
      agonist profile.
AB  - The amino acids glutamate (Glu) and glycine (Gly) trigger large, rapid rises in
      cytosolic Ca(2+) concentration and a concomitant rise in membrane potential
      (depolarization) in plants. The possibility that plant homologs of neuronal
      ionotropic glutamate receptors mediate these neuron-like ionic responses was
      tested in Arabidopsis (Arabidopsis thaliana) seedlings using a combination of
      Ca(2+) measurements, electrophysiology, and reverse genetics. The membrane
      depolarization triggered by Glu was greatly reduced or completely blocked in some
      conditions by mutations in GLR3.3, one of the 20 GLR genes in Arabidopsis. The
      same mutations completely blocked the associated rise in cytosolic Ca(2+). These
      results genetically demonstrate the participation of a glutamate receptor in the
      rapid ionic responses to an amino acid. The GLR3.3-independent component of the
      depolarization required Glu concentrations above 25 mum, did not display
      desensitization, and was strongly suppressed by increasing extracellular pH. It
      is suggested to result from H(+)-amino acid symport. Six amino acids commonly
      present in soils (Glu, Gly, alanine, serine, asparagine, and cysteine) as well as
      the tripeptide glutathione (gamma-glutamyl-cysteinyl-Gly) were found to be strong
      agonists of the GLR3.3-mediated responses. All other amino acids induced a small
      depolarization similar to the non-GLR, putative symporter component and in most
      cases evoked little or no Ca(2+) rise. From these results it may be concluded
      that sensing of six amino acids in the rhizosphere and perhaps extracellular
      peptides is coupled to Ca(2+) signaling through a GLR-dependent mechanism
      homologous to a fundamental component of neuronal signaling.

PMID- 17012404
TI  - Regulation of seed size by hypomethylation of maternal and paternal genomes.
AB  - DNA methylation is an epigenetic modification of cytosine that is important for
      silencing gene transcription and transposons, gene imprinting, development, and
      seed viability. DNA METHYLTRANSFERASE1 (MET1) is the primary maintenance DNA
      methyltransferase in Arabidopsis (Arabidopsis thaliana). Reciprocal crosses
      between antisense MET1 transgenic and wild-type plants show that DNA
      hypomethylation has a parent-of-origin effect on seed size. However, due to the
      dominant nature of the antisense MET1 transgene, the parent with a hypomethylated
      genome, its gametophyte, and both the maternal and paternal genomes of the F(1)
      seed become hypomethylated. Thus, the distinct role played by hypomethylation at
      each generation is not known. To address this issue, we examined F(1) seed from
      reciprocal crosses using a loss-of-function recessive null allele, met1-6.
      Crosses between wild-type and homozygous met1-6 parents show that hypomethylated
      maternal and paternal genomes result in significantly larger and smaller F(1)
      seeds, respectively. Our analysis of crosses between wild-type and heterozygous
      MET1/met1-6 parents revealed that hypomethylation in the female or male
      gametophytic generation was sufficient to influence F(1) seed size. A recessive
      mutation in another gene that dramatically reduces DNA methylation, DECREASE IN
      DNA METHYLATION1, also causes parent-of-origin effects on F(1) seed size. By
      contrast, recessive mutations in genes that regulate a smaller subset of DNA
      methylation (CHROMOMETHYLASE3 and DOMAINS REARRANGED METHYLTRANSFERASES1 and 2)
      had little effect on seed size. Collectively, these results show that maternal
      and paternal genomes play distinct roles in the regulation of seed size in
      Arabidopsis.

PMID- 17012405
TI  - Light-induced expression of a MYB gene regulates anthocyanin biosynthesis in red
      apples.
AB  - Anthocyanins are secondary metabolites found in higher plants that contribute to
      the colors of flowers and fruits. In apples (Malus domestica Borkh.), several
      steps of the anthocyanin pathway are coordinately regulated, suggesting control
      by common transcription factors. A gene encoding an R2R3 MYB transcription factor
      was isolated from apple (cv Cripps' Pink) and designated MdMYB1. Analysis of the
      deduced amino acid sequence suggests that this gene encodes an ortholog of
      anthocyanin regulators in other plants. The expression of MdMYB1 in both
      Arabidopsis (Arabidopsis thaliana) plants and cultured grape cells induced the
      ectopic synthesis of anthocyanin. In the grape (Vitis vinifera) cells MdMYB1
      stimulated transcription from the promoters of two apple genes encoding
      anthocyanin biosynthetic enzymes. In ripening apple fruit the transcription of
      MdMYB1 was correlated with anthocyanin synthesis in red skin sectors of fruit.
      When dark-grown fruit were exposed to sunlight, MdMYB1 transcript levels
      increased over several days, correlating with anthocyanin synthesis in the skin.
      MdMYB1 gene transcripts were more abundant in red skin apple cultivars compared
      to non-red skin cultivars. Several polymorphisms were identified in the promoter
      of MdMYB1. A derived cleaved amplified polymorphic sequence marker designed to
      one of these polymorphisms segregated with the inheritance of skin color in
      progeny from a cross of an unnamed red skin selection (a sibling of Cripps' Pink)
      and the non-red skin cultivar Golden Delicious. We conclude that MdMYB1
      coordinately regulates genes in the anthocyanin pathway and the expression level
      of this regulator is the genetic basis for apple skin color.

PMID- 17012406
TI  - The cyclin-dependent kinase inhibitor Orysa;KRP1 plays an important role in seed
      development of rice.
AB  - Kip-related proteins (KRPs) play a major role in the regulation of the plant cell
      cycle. We report the identification of five putative rice (Oryza sativa) proteins
      that share characteristic motifs with previously described plant KRPs. To
      investigate the function of KRPs in rice development, we generated transgenic
      plants overexpressing the Orysa;KRP1 gene. Phenotypic analysis revealed that
      overexpressed KRP1 reduced cell production during leaf development. The reduced
      cell production in the leaf meristem was partly compensated by an increased cell
      size, demonstrating the existence of a compensatory mechanism in monocot species
      by which growth rate is less reduced than cell production, through cell
      expansion. Furthermore, Orysa;KRP1 overexpression dramatically reduced seed
      filling. Sectioning through the overexpressed KRP1 seeds showed that KRP
      overproduction disturbed the production of endosperm cells. The decrease in the
      number of fully formed seeds was accompanied by a drop in the endoreduplication
      of endosperm cells, pointing toward a role of KRP1 in connecting endocycle with
      endosperm development. Also, spatial and temporal transcript detection in
      developing seeds suggests that Orysa;KRP1 plays an important role in the exit
      from the mitotic cell cycle during rice grain formation.

PMID- 17012407
TI  - The floral organ number4 gene encoding a putative ortholog of Arabidopsis
      CLAVATA3 regulates apical meristem size in rice.
AB  - To understand the molecular mechanism regulating meristem development in the
      monocot rice (Oryza sativa), we describe here the isolation and characterization
      of three floral organ number4 (fon4) alleles and the cloning of the FON4 gene.
      The fon4 mutants showed abnormal enlargement of the embryonic and vegetative
      shoot apical meristems (SAMs) and the inflorescence and floral meristems. Likely
      due to enlarged SAMs, fon4 mutants produced thick culms (stems) and increased
      numbers of both primary rachis branches and floral organs. We identified FON4
      using a map-based cloning approach and found it encodes a small putatively
      secreted protein, which is the putative ortholog of the Arabidopsis (Arabidopsis
      thaliana) CLAVATA3 (CLV3) gene. FON4 transcripts mainly accumulated in the small
      group of cells at the apex of the SAMs, whereas the rice ortholog of CLV1 (FON1)
      is expressed throughout the SAMs, suggesting that the putative FON4 ligand might
      be sequestered as a possible mechanism for rice meristem regulation. Exogenous
      application of the peptides FON4p and CLV3p corresponding to the CLV3/ESR-related
      (CLE) motifs of FON4 and CLV3, respectively, resulted in termination of SAMs in
      rice, and treatment with CLV3p caused consumption of both rice and Arabidopsis
      root meristems, suggesting that the CLV pathway in limiting meristem size is
      conserved in both rice and Arabidopsis. However, exogenous FON4p did not have an
      obvious effect on limiting both rice and Arabidopsis root meristems, suggesting
      that the CLE motifs of Arabidopsis CLV3 and FON4 are potentially functionally
      divergent.

PMID- 17012408
TI  - A novel function for the cathepsin D inhibitor in tomato.
AB  - Proteinaceous aspartic proteinase inhibitors are rare in nature and are described
      in only a few plant species. One of them corresponds to a family of cathepsin D
      inhibitors (CDIs) described in potato (Solanum tuberosum), involving up to 15
      isoforms with a high sequence similarity. In this work, we describe a tomato
      (Solanum lycopersicum) wound-inducible protein called jasmonic-induced protein 21
      (JIP21). Sequence analysis of its cDNA predicted a putative function as a CDI.
      The JIP21 gene, whose protein has been demonstrated to be glycosylated, is
      constitutively expressed in flowers, stem, and fruit, and is inducible to high
      levels by wounding and methyl jasmonate in leaves of tomato plants. The genomic
      sequence of JIP21 shows that the gene is intronless and reveals the presence of
      both a methyl jasmonate box (TGACT) and a G-box (CACGT) in the promoter. In
      contrast to the presumed role of JIP21 based on sequence analysis, a detailed
      biochemical characterization of the purified protein uncovers a different
      function as a strong chymotrypsin inhibitor, which questions the previously
      predicted inhibitory activity against aspartic proteinases. Moreover, Egyptian
      cotton worm (Spodoptera littoralis) larvae fed on transgenic tomato plants
      overexpressing JIP21 present an increase in mortality and a delay in growth when
      compared with larvae fed on wild-type plants. These larvae belong to the
      Lepidoptera family whose main digestive enzymes have been described as being Ser
      proteases. All these results support the notion that tomato JIP21 should be
      considered as a chymotrypsin inhibitor belonging to the Ser proteinase inhibitors
      rather than a CDI. Therefore, we propose to name this protein tomato chymotrypsin
      inhibitor 21 (TCI21).

PMID- 17012409
TI  - CO2 sensing at ocean surface mediated by cAMP in a marine diatom.
AB  - Marine diatoms are known to be responsible for about a quarter of global primary
      production and their photosynthesis is sustained by inorganic carbon
      concentrating mechanisms and/or C(4) metabolism. Activities of the inorganic
      carbon-concentrating mechanism are attenuated under enriched [CO(2)]; however,
      impacts of this factor on primary productivity and the molecular mechanisms of
      CO(2) responses in marine diatoms are unknown. In this study, transgenic cells
      were generated of the marine diatom Phaeodactylum tricornutum by the introduction
      of a beta-glucuronidase reporter gene under the control of an intrinsic CO(2)
      responsive promoter, which is the sequence between -80 to +61 relative to the
      transcription start site of a chloroplastic-carbonic anhydrase gene, ptca1,
      obtained from P. tricornutum. The activity of the ptca1 promoter was effectively
      repressed in air-level CO(2) by treating cells with a 1.0 mm cAMP analog,
      dibutyryl cAMP, or a cAMP phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine. Deletion of the intrinsic cAMP-response element from the ptca1
      promoter caused a lack of repression of the reporter gene uidA, even under
      elevated [CO(2)] and a null phenotype to the strong repressive effects of
      dibutyryl cAMP and 3-isobutyl-1-methylxanthine on the ptca1 promoter. Deletion of
      the cAMP-response element was also shown to cause derepression of the uidA
      reporter gene in the dark. These results indicate that the cytosolic cAMP level
      increases under elevated [CO(2)] and represses the ptca1 promoter. This strongly
      suggests the participation of cAMP metabolism, presumably at the cytosolic level,
      in controlling CO(2)-acquisition systems under elevated [CO(2)] at the ocean
      surface in a marine diatom.

PMID- 17012410
TI  - Developmental and embryo axis regulation of gibberellin biosynthesis during
      germination and young seedling growth of pea.
AB  - The expression patterns of five genes (PsGA20ox1, PsGA20ox2, PsGA3ox1, PsGA2ox1,
      and PsGA2ox2) encoding five regulatory gibberellin (GA) biosynthesis enzymes (two
      GA 20-oxidases, a GA 3beta-hydroxylase, and two GA 2beta-hydroxylases) were
      examined to gain insight into how these genes coordinate GA biosynthesis during
      germination and early postgermination stages of the large-seeded dicotyledonous
      plant pea (Pisum sativum). At the time the developing embryo fills the seed coat,
      high mRNA levels of PsGA20ox2 (primarily responsible for conversion of C20-GAs to
      GA(20)), PsGA2ox1 (primarily responsible for conversion of GA(20) to GA(29)), and
      PsGA2ox2 (primarily responsible for conversion of GA(1) to GA(8)) were detected
      in the seeds, along with high GA(20) and GA(29) levels, the enzymatic products of
      these genes. Embryo maturation was accompanied by a large reduction in PsGA20ox2
      and PsGA2ox1 mRNA and lower GA(20) and GA(29) levels. However, PsGA2ox2
      transcripts remained high. Following seed imbibition, GA(20) levels in the
      cotyledons decreased, while PsGA3ox1 mRNA and GA(1) levels increased, implying
      that GA(20) was being used for de novo synthesis of GA(1). The presence of the
      embryo axis was required for stimulation of cotyledonary GA(1) synthesis at the
      mRNA and enzyme activity levels. As the embryo axis doubled in size, PsGA20ox1
      and PsGA3ox1 transcripts increased, both GA(1) and GA(8) were detectable,
      PsGA2ox2 transcripts decreased, and PsGA2ox1 transcripts remained low.
      Cotyledonary-, root-, and shoot-specific expression of these GA biosynthesis
      genes and the resultant endogenous GA profiles support a key role for de novo GA
      biosynthesis in each organ during germination and early seedling growth of pea.

PMID- 17012412
TI  - Obesity and joint replacement.
AB  - There has been considerable discussion as to the influence of obesity on the
      indications for, and the outcome after, joint replacement. Attempts have been
      made to withhold funding for such procedures in those who are overweight. What is
      the justification for this? This editorial examines the current evidence
      concerning the influence of obesity on joint replacement and suggests that it is
      only in the morbidly obese, with a body mass index > 40 kg/m(2), that significant
      contraindications to operation are present.

PMID- 17012411
TI  - Characterization of a two-component high-affinity nitrate uptake system in
      Arabidopsis. Physiology and protein-protein interaction.
AB  - The identification of a family of NAR2-type genes in higher plants showed that
      there was a homolog in Arabidopsis (Arabidopsis thaliana), AtNAR2.1. These genes
      encode part of a two-component nitrate high-affinity transport system (HATS). As
      the Arabidopsis NRT2 gene family of nitrate transporters has been characterized,
      we tested the idea that AtNAR2.1 and AtNRT2.1 are partners in a two-component
      HATS. Results using the yeast split-ubiquitin system and Xenopus oocyte
      expression showed that the two proteins interacted to give a functional HATS. The
      growth and nitrogen (N) physiology of two Arabidopsis gene knockout mutants,
      atnrt2.1-1 and atnar2.1-1, one for each partner protein, were compared. Both
      types of plants had lost HATS activity at 0.2 mm nitrate, but the effect was more
      severe in atnar2.1-1 plants. The relationship between plant N status and nitrate
      transporter expression revealed a pattern that was characteristic of N deficiency
      that was again stronger in atnar2.1-1. Plants resulting from a cross between both
      mutants (atnrt2.1-1 x atnar2.1-1) showed a phenotype like that of the atnar2.1-1
      mutant when grown in 0.5 mm nitrate. Lateral root assays also revealed growth
      differences between the two mutants, confirming that atnar2.1-1 had a stronger
      phenotype. To show that the impaired HATS did not result from the decreased
      expression of AtNRT2.1, we tested if constitutive root expression of a tobacco
      (Nicotiana plumbaginifolia) gene, NpNRT2.1, previously been shown to complement
      atnrt2.1-1, can restore HATS to the atnar2.1-1 mutant. These plants did not
      recover wild-type nitrate HATS. Taken together, these results show that AtNAR2.1
      is essential for HATS of nitrate in Arabidopsis.

PMID- 17012413
TI  - Principles of fixation of osteoporotic fractures.
AB  - Despite advances in the prevention and treatment of osteoporotic fractures, their
      prevalence continues to increase. Their operative treatment remains a challenge
      for the surgeon, often with unpredictable outcomes. This review highlights the
      current aspects of management of these fractures and focuses on advances in
      implant design and surgical technique.

PMID- 17012414
TI  - Management of arthritis of the hip in the young adult.
AB  - Arthritis of the hip in the young adult can be a disabling condition. Recent
      years have witnessed extensive research related to the management of this
      condition. This article reviews the current status with regard to aetiology,
      diagnosis and treatment of arthritis of the hip in the young adult.

PMID- 17012415
TI  - The outcome of total hip replacement in obese and non-obese patients at 10- to 18
      years.
AB  - We studied a consecutive series of 285 uncemented total hip replacements in 260
      patients using the Taperloc femoral component and the T-Tap acetabular component.
      The outcome of every hip was determined in both living and deceased patients. A
      complete clinical and radiological follow-up was obtained for 209 hips in 188
      living patients, followed for a mean of 14.5 years (10 to 18.9). They were
      divided into two groups, obese and non-obese, as determined by their body mass
      index. There were 100 total hip replacements in 89 patients in the obese cohort
      (body mass index > or = 30 kg/m(2)), and 109 in 99 non-obese (body mass index <
      30 kg/m(2)) patients. A subgroup analysis of 31 patients of normal weight (body
      mass index 20 kg/m(2) to 25 kg/m(2)) (33 hips) and 26 morbidly obese patients
      (body mass index > or = 35 kg/m(2)) (30 hips) was also carried out. In the obese
      group five femoral components (5%) were revised and one (1%) was loose by
      radiological criteria. Femoral cortical osteolysis was seen in eight hips (8%).
      The acetabular component was revised in 57 hips (57%) and a further 17 (17%) were
      loose. The mean Harris hip score improved from 52 (30 to 66) pre-operatively to
      89 (49 to 100) at final follow-up. Peri-operative complications occurred in seven
      patients (7%). In the non-obese group six (6%) femoral components were revised
      and one (1%) was loose. Femoral cortical osteolysis occurred in six hips (6%).
      The acetabular component was revised in 72 hips (66%) and a further 18 (17%) were
      loose. The mean Harris hip score increased from 53 (25 to 73) prior to surgery to
      89 (53 to 100) at the time of each patient's final follow-up radiograph. No
      statistically significant difference was identified between the obese and non
      obese patients with regards to clinical and radiological outcome or
      complications. The subgroup analysis of patients of normal weight and those who
      were morbidly obese showed no statistically significant difference in the rate of
      revision of either component. Our findings suggest there is no evidence to
      support withholding total hip replacement from obese patients with arthritic hips
      on the grounds that their outcome will be less satisfactory than those who are
      not obese.

PMID- 17012416
TI  - Outcome of Charnley total hip replacement across a single health region in
      England. The results at ten years from a regional arthroplasty register.
AB  - Using the Trent regional arthroplasty register, we analysed the survival at ten
      years of 1198 consecutive Charnley total hip replacements carried out across a
      single health region of the United Kingdom in 1990. At ten years, information
      regarding outcome was available for 1001 hips (83.6%). The crude revision rate
      was 6.2% (62 of 1001) and the cumulative survival rate with revision of the
      components as an end-point was 93.1%. At five years, a review of this series of
      patients identified gross radiological failure in 25 total hip replacements which
      had previously been unrecognised. At ten years the outcome was known for 18 of
      these 25 patients (72%), of whom 13 had not undergone revision. This is the first
      study to assess the survival at ten years for the primary Charnley total hip
      replacement performed in a broad cross-section of hospitals in the United
      Kingdom, as opposed to specialist centres. Our results highlight the importance
      of the arthroplasty register in identifying the long-term outcome of hip
      prostheses.

PMID- 17012417
TI  - A custom-made prosthesis attached to an existing femoral component for the
      treatment of peri- and sub-prosthetic fracture.
AB  - Peri- and sub-prosthetic fractures, or pathological fractures below an existing
      well-fixed femoral component, with or without an ipsilateral knee replacement,
      present a difficult surgical challenge. We describe a simple solution, in which a
      custom-made prosthesis with a cylindrical design is cemented proximally to the
      stem of an existing, well-fixed femoral component. This effectively treats the
      fracture without sacrificing the good hip. We describe five patients with a mean
      age of 73 years (60 to 81) and a mean follow-up of 47 months (6 to 108). The mean
      overlap of the prosthesis over the femoral component was 7.5 cm (5.5 to 10).
      There have been no mechanical failures, no new infections and no re-operations.
      We suggest that in highly selected cases, in which conventional fixation is not
      feasible, this technique offers a durable option and avoids the morbidity of a
      total femoral replacement.

PMID- 17012418
TI  - Patient-related predictors of implant failure after primary total hip replacement
      in the initial, short- and long-terms. A nationwide Danish follow-up study
      including 36,984 patients.
AB  - We examined the association between patient-related factors and the risk of
      initial, short- and long-term implant failure after primary total hip
      replacement. We used data from the Danish Hip Arthroplasty Registry between 1
      January 1995 and 31 December 2002, which gave us a total of 36 984 patients.
      Separate analyses were carried out for three follow-up periods: 0 to 30 days, 31
      days to six months (short term), and six months to 8.6 years after primary total
      hip replacement (long term). The outcome measure was defined as time to failure,
      which included re-operation with open surgery for any reason. Male gender and a
      high Charlson co-morbidity index score were strongly predictive for failure,
      irrespective of the period of follow-up. Age and diagnosis at primary total hip
      replacement were identified as time-dependent predictive factors of failure.
      During the first 30 days after primary total hip replacement, an age of 80 years
      or more and hip replacement undertaken as a sequela of trauma, for avascular
      necrosis or paediatric conditions, were associated with an increased risk of
      failure. However, during six months to 8.6 years after surgery, being less than
      60 years old was associated with an increased risk of failure, whereas none of
      the diagnoses for primary total hip replacement appeared to be independent
      predictors.

PMID- 17012419
TI  - Clinical and radiological outcome of total hip replacement five years after
      pamidronate therapy. A trial extension.
AB  - Bisphosphonates reduce peri-prosthetic bone loss in the short term after total
      hip replacement but the mid- and longer term effects are not known. The aims of
      this randomised trial were to examine the effect of a single dose of 90 mg of
      pamidronate on the clinical and radiological outcome and peri-prosthetic bone
      mineral density in 50 patients (56 hips) over a five-year period, following total
      hip replacement. At five years, 37 patients (42 hips) returned for assessment.
      The Harris hip scores were similar in the pamidronate and placebo groups
      throughout the study. Also at five years, four patients, two from each group had
      osteolytic lesions on plain radiography. These were located around the acetabular
      component in three patients and in the femoral calcar in one. The femoral and
      acetabular peri-prosthetic bone mineral density in the pamidronate group and the
      control group was similar at five years. Pamidronate given as a single post
      operative dose does not appear to influence the clinical outcome or prevent the
      development of osteolytic lesions at five years after total hip replacement.

PMID- 17012420
TI  - The impact of tobacco use and body mass index on the length of stay in hospital
      and the risk of post-operative complications among patients undergoing total hip
      replacement.
AB  - We carried out a retrospective cohort study of 3309 patients undergoing primary
      total hip replacement to examine the impact of tobacco use and body mass index on
      the length of stay in hospital and the risk of short term post-operative
      complications. Heavy tobacco use was associated with an increased risk of
      systemic post-operative complications (p = 0.004). Previous and current smokers
      had a 43% and 56% increased risk of systemic complications, respectively, when
      compared with non-smokers. In heavy smokers, the risk increased by 121%. A high
      body mass index was significantly associated with an increased mean length of
      stay in hospital of between 4.7% and 7%. The risk of systemic complications was
      increased by 58% in the obese. Smoking and body mass index were not significantly
      related to the development of local complications. Greater efforts should be
      taken to reduce the impact of preventable life style factors, such as smoking and
      high body mass index, on the post-operative course of total hip replacement.

PMID- 17012421
TI  - Total knee replacement in morbidly obese patients. Results of a prospective,
      matched study.
AB  - The results of 41 consecutive total knee replacements performed on morbidly obese
      patients with a body mass index > 40 kg/m(2), were compared with a matched group
      of 41 similar procedures carried out in non-obese patients (body mass index < 30
      kg/m(2)). The groups were matched for age, gender, diagnosis, type of prosthesis,
      laterality and pre-operative Knee Society Score. We prospectively followed up the
      patients for a mean of 38.5 months (6 to 66). No patients were lost to follow-up.
      At less than four years after operation, the results were worse in the morbidly
      obese group compared with the non-obese, as demonstrated by inferior Knee Society
      Scores (mean knee score 85.7 and 90.5 respectively, p = 0.08; mean function score
      75.6 and 83.4, p = 0.01), a higher incidence of radiolucent lines on post
      operative radiographs (29% and 7%, respectively, p = 0.02), a higher rate of
      complications (32% and 0%, respectively, p = 0.001) and inferior survivorship
      using revision and pain as end-points (72.3% and 97.6%, respectively, p = 0.02).
      Patients with a body mass index > 40 kg/m(2) should be advised to lose weight
      prior to total knee replacement and to maintain weight reduction. They should
      also be counselled regarding the inferior results which may occur if they do not
      lose weight before surgery.

PMID- 17012422
TI  - Evaluation of the flexion gap by axial radiography of the distal femur.
AB  - The shape of the flexion gap in 20 normal knees was evaluated by axial
      radiography of the distal femur, and the results compared with those obtained in
      a previous study by MRI. The observed asymmetry was reduced by 29% using
      radiography, with a mean value of 3.6 degrees (1.5 degrees to 6.3 degrees)
      compared with that obtained by MRI of 5.1 degrees (2.6 degrees to 9.5 degrees), a
      mean discrepancy of 1.49 degrees. The results obtained by radiography and MRI
      showed a strong correlation (r = 0.78). Axial radiography is acceptable for the
      evaluation of the flexion gap and is less expensive and more comfortable to
      perform than MRI. Additionally, no metallic artefact occurs when the radiological
      method is used for assessment after arthroplasty.

PMID- 17012423
TI  - Trochleaplasty for recurrent patellar dislocation in association with trochlear
      dysplasia. A 4- to 14-year follow-up study.
AB  - We investigated the clinical and radiological outcome of trochleaplasty for
      recurrent patellar dislocation in association with trochlear dysplasia in 38
      consecutive patients (45 knees) with a mean follow-up of 8.3 years (4 to 14).
      None had recurrence of dislocation after trochleaplasty. Post-operatively,
      patellofemoral pain, present pre-operatively in only 35 knees, became worse in 15
      (33.4%), remained unchanged in four (8.8%) and improved in 22 (49%). Four knees
      which had no pain pre-operatively (8.8%) continued to have no pain. A total of 33
      knees were available for radiological assessment. Post-operatively, all but two
      knees (93.9%) had correction of trochlear dysplasia radiologically but
      degenerative changes of the patellofemoral joint developed in 30% (10) of the
      knees. We conclude that recurrent patellar dislocation associated with trochlear
      dysplasia can be treated successfully by trochleaplasty, but the impact on
      patellofemoral pain and the development of patellofemoral osteoarthritis is less
      predictable. Overall, subjective patient satisfaction with restored
      patellofemoral stability after trochleaplasty appeared to outweigh its possible
      sequelae.

PMID- 17012424
TI  - Inverted V-shaped high tibial osteotomy compared with closing-wedge high tibial
      osteotomy for osteoarthritis of the knee. Ten-year follow-up result.
AB  - We compared the results ten years after an inverted V-shaped high tibial
      osteotomy with those of a historical series of conventional closing-wedge
      osteotomies. The closing-wedge series consisted of 56 knees in 51 patients with a
      mean follow-up of 11 years (10 to 15). The inverted V-shaped osteotomy was
      evaluated in 48 knees in 43 patients at a mean follow-up of 14 years (10 to 19).
      All the patients were scored using the Japanese Orthopaedic Association rating
      scale for osteoarthritis of the knee and radiological assessment. The pre
      operative grade of osteoarthritis was similar in both groups. Post-operatively,
      the knee function score was graded as satisfactory in 63% (35) of the closing
      wedge group but in 89% (43) of the inverted V-shaped osteotomy group. Post
      operative radiological examination showed that delayed union and loss of
      correction occurred more often after a closing-wedge osteotomy than after an
      inverted V-shaped procedure. Our study suggests that the inverted V-shaped
      osteotomy may offer more dependable long-term results than traditional closing
      wedge osteotomy.

PMID- 17012425
TI  - Single-stage revision of peri-prosthetic infection following total elbow
      replacement.
AB  - This study reviews the predisposing features, the clinical, and laboratory
      findings at the time of diagnosis and the results of single-stage revision of
      prosthetic replacement of the elbow for infection. Deep infection occurred in six
      of 305 (1.9%) primary total elbow replacements. The mean follow-up after revision
      was 6.8 years (6 months to 16 years) and the mean age at the time of revision was
      62.7 years (56 to 74). All six cases with infection had rheumatoid arthritis and
      had received steroid therapy. The infective organism was Staphylococcus aureus.
      Four of the six elbows had a developed radiolucency around one component or the
      other. Successful single-stage exchange arthroplasty was carried out with
      antibiotic-loaded cement in five of the six cases. In one, the revision
      prosthesis had to be removed following recurrence of the infection. The
      functional result was good in three elbows, fair in one, poor in one and fair in
      the resection arthroplasty.

PMID- 17012426
TI  - Comparison between external fixation and sliding hip screw in the management of
      trochanteric fracture of the femur in Nepal.
AB  - We conducted a randomised controlled trial to compare external fixation of
      trochanteric fractures of the femur with the more costly option of the sliding
      hip screw. Patients in both groups were matched for age (mean 67 years, 50 to
      100) and gender. We excluded all pathological fractures, patients presenting at
      more than one week, fractures with subtrochanteric extension or reverse
      obliquity, multiple fractures or any bone and joint disease interfering with
      rehabilitation. The interval between injury and operation, the duration of
      surgery, the amount of blood loss, the length of hospital stay and the cost of
      treatment were all significantly higher in the sliding hip screw group (p <
      0.05). The time to union, range of movement, mean Harris hip scores and Western
      Ontario and McMaster University knee scores were comparable at six months. The
      number of patients showing shortening or malrotation was too small to show a
      significant difference between the groups. Pin-track infection occurred in 18
      patients (60%) treated with external fixation, whereas there was a single case of
      wound infection (3.3%) in the sliding hip screw group.

PMID- 17012427
TI  - A score for predicting salvage and outcome in Gustilo type-IIIA and type-IIIB
      open tibial fractures.
AB  - Limb-injury severity scores are designed to assess orthopaedic and vascular
      injuries. In Gustilo type-IIIA and type-IIIB injuries they have poor sensitivity
      and specificity to predict salvage or outcome. We have designed a trauma score to
      grade the severity of injury to the covering tissues, the bones and the
      functional tissues, grading the three components from one to five. Seven comorbid
      conditions known to influence the management and prognosis have been given a
      score of two each. The score was validated in 109 consecutive open injuries of
      the tibia, 42 type-IIIA and 67 type-IIIB. The total score was used to assess the
      possibilities of salvage and the outcome was measured by dividing the injuries
      into four groups according to their scores as follows: group I scored less than
      5, group II 6 to 10, group III 11 to 15 and group IV 16 or more. A score of 14 to
      indicate amputation had the highest sensitivity and specificity. Our trauma score
      compared favourably with the Mangled Extremity Severity score in sensitivity (98%
      and 99%), specificity (100% and 17%), positive predictive value (100% and 97.5%)
      and negative predictive value (70% and 50%), respectively. A receiver-operating
      characteristic curve constructed for 67 type-IIIB injuries to assess the
      efficiency of the scores to predict salvage, showed that the area under the curve
      for this score was better (0.988 (+/- 0.013 SEM)) than the Mangled Extremity
      Severity score (0.938 (+/- 0.039 SEM)). All limbs in group IV and one in group
      III underwent amputation. Of the salvaged limbs, there was a significant
      difference in the three groups for the requirement of a flap for wound cover, the
      time to union, the number of surgical procedures required, the total days as an
      in-patient and the incidence of deep infection (p < 0.001 for all). The
      individual scores for covering and functional tissues were also found to offer
      specific guidelines in the management of these complex injuries. The scoring
      system was found to be simple in application and reliable in prognosis for both
      limb-salvage and outcome measures in type-IIIA and type-IIIB open injuries of the
      tibia.

PMID- 17012428
TI  - Titanium elastic nailing of fractures of the femur in children. Predictors of
      complications and poor outcome.
AB  - Between 1996 and 2003 six institutions in the United States and France
      contributed a consecutive series of 234 fractures of the femur in 229 children
      which were treated by titanium elastic nailing. Minor or major complications
      occurred in 80 fractures. Full information was available concerning 230
      fractures, of which the outcome was excellent in 150 (65%), satisfactory in 57
      (25%), and poor in 23 (10%). Poor outcomes were due to leg-length discrepancy in
      five fractures, unacceptable angulation in 17, and failure of fixation in one.
      There was a statistically significant relationship (p = 0.003) between age and
      outcome, and the odds ratio for poor outcome was 3.86 for children aged 11 years
      and older compared with those below this age. The difference between the weight
      of children with a poor outcome and those with an excellent or satisfactory
      outcome was statistically significant (54 kg vs 39 kg; p = 0.003). A poor outcome
      was five times more likely in children who weighed more than 49 kg.

PMID- 17012429
TI  - A knee-sparing distal femoral endoprosthesis using hydroxyapatite-coated
      extracortical plates. Preliminary results.
AB  - We used a knee-sparing distal femoral endoprosthesis in young patients with
      malignant bone tumours of the distal femur in whom it was possible to resect the
      tumour and to preserve the distal femoral condyles. The proximal shaft of the
      endoprosthesis had a coated hydroxyapatite collar, while the distal end had
      hydroxyapatite-coated extracortical plates to secure it to the small residual
      femoral condylar fragment. We reviewed the preliminary results of this
      endoprosthesis in eight patients with primary bone tumours of the distal femur.
      Their mean age at surgery was 17.years (14 to 21). The mean follow-up was 24
      months (20 to 31). At final follow-up the mean flexion at the knee was 102
      degrees (20 degrees to 120 degrees) and the mean Musculoskeletal Tumour Society
      score was 80% (57% to 96.7%). There was excellent osteointegration at the
      prosthesis-proximal bone interface with formation of new bone around the
      hydroxyapatite collar. The prosthesis allowed preservation of the knee and
      achieved a good functional result. Formation of new bone and remodelling at the
      interface make the implant more secure. Further follow-up is required to
      determine the long-term structural integrity of the prosthesis.

PMID- 17012430
TI  - Combined femoral and Chiari osteotomies for reconstruction of the painful
      subluxation or dislocation of the hip in cerebral palsy. A long-term outcome
      study.
AB  - In order to treat painful subluxation or dislocation secondary to cerebral palsy,
      11 patients (12 hips) underwent combined femoral and Chiari pelvic osteotomies
      with additional soft-tissue releases at a mean age of 14.1 years (9.1 to 17.8).
      Relief of pain, improvement in movement of the hip, and in sitting posture, and
      ease of perineal care were recorded in all, and were maintained at a mean follow
      up of 13.1 years (8 to 17.5). The improvement in general mobility was marginal,
      but those who were able to walk benefited the most. The radiological measurements
      made before operation were modified afterwards to use the lateral margin of the
      neoacetabulum produced by the pelvic osteotomy. The radiological migration index
      improved from a mean of 80.6% (61% to 100%) to 13.7% (0% to 33%) (p < 0.0001).
      The mean changes in centre edge angle and Sharp's angle were 72 degrees (56
      degrees to 87 degrees; p < 0.0001) and 12.3 degrees (9 degrees to 15.6 degrees; p
      < 0.0001), respectively. Radiological evidence of progressive arthritic change
      was seen in one hip, in which only a partial reduction had been achieved, and
      there was early narrowing of the joint space in another. Painless heterotopic
      ossification was observed in one patient with athetoid quadriplegia. In seven
      hips the lateral Kawamura approach, elevating the greater trochanter, provided
      exposure for both osteotomies and allowed the construction of a dome-shaped iliac
      osteotomy, while protecting the sciatic nerve.

PMID- 17012431
TI  - Outcomes of subcapital cuneiform osteotomy for the treatment of severe slipped
      capital femoral epiphysis after skeletal maturity.
AB  - We reviewed prospectively, after skeletal maturity, a series of 24 patients (25
      hips) with severe acute-on-chronic slipped capital femoral epiphysis which had
      been treated by subcapital cuneiform osteotomy. Patients were followed up for a
      mean of 8 years, 3 months (2 years, 5 months to 16 years, 4 months). Bedrest with
      'slings and springs' had been used for a mean of 22 days (19 to 35) in 22
      patients, and bedrest alone in two, before definitive surgery. The Iowa hip
      score, the Harris hip score and Boyer's radiological classification for
      degenerative disease were used. The mean Iowa hip score at follow-up was 93.7 (69
      to 100) and the mean Harris hip score 95.6 (78 to 100). Degenerative joint
      changes were graded as 0 in 19 hips, grade 1 in four and grade 2 in two. The rate
      of avascular necrosis was 12% (3 of 25) and the rate of chondrolysis was 16% (4
      of 25). We conclude that after a period of bed rest with slings and springs for
      three weeks to gain stability, subcapital cuneiform osteotomy for severe acute-on
      chronic slipped capital femoral epiphysis is a satisfactory method of treatment
      with an acceptable rate of complication.

PMID- 17012432
TI  - Treatment of idiopathic club foot using the Ponseti method. Initial experience.
AB  - We report our initial experience of using the Ponseti method for the treatment of
      congenital idiopathic club foot. Between November 2002 and November 2004 we
      treated 100 feet in 66 children by this method. The standard protocol described
      by Ponseti was used except that, when necessary, percutaneous tenotomy of tendo
      Achillis were performed under general anaesthesia in the operating theatre and
      not under local anaesthesia in the out-patient department. The Pirani score was
      used for assessment and the mean follow-up time was 18 months (6 to 30). The
      results were also assessed in terms of the number of casts applied, the need for
      tenotomy of tendo Achillis and recurrence of the deformity. Tenotomy was required
      in 85 of the 100 feet. There was a failure to respond to the initial regimen in
      four feet which then required extensive soft-tissue release. Of the 96 feet which
      responded to initial casting, 31 (32%) had a recurrence, 16 of which were
      successfully treated by repeat casting and/or tenotomy and/or transfer of the
      tendon of tibialis anterior. The remaining 15 required extensive soft-tissue
      release. Poor compliance with the foot-abduction orthoses (Denis Browne splint)
      was thought to be the main cause of failure in these patients.

PMID- 17012433
TI  - Isolated tuberculosis of the coccyx.
AB  - Vertebral disease constitutes approximately 50% of all skeletal tuberculosis. We
      describe a patient who developed a discharging sinus at the tip of the coccyx.
      Extensive examination revealed isolated tuberculosis of the coccyx. Although
      rare, the condition should be suspected in patients presenting with a chronic
      sinus in the sacrococcygeal area and a lytic lesion in the coccyx on CT or MRI,
      particularly in the developing world.

PMID- 17012434
TI  - Incomplete discoid glenoid labrum combined with a ganglion cyst of the
      spinoglenoid notch.
AB  - In a 41-year-old man, right-sided infraspinatus muscle weakness was associated
      with compression of the suprascapular nerve caused by a spinoglenoid ganglion
      cyst. The lesion was confirmed using electromyography and MRI. In addition,
      arthroscopy showed an incomplete discoid labrum. The free inner edge of the
      labrum was removed as in a meniscectomy of a discoid meniscus in the knee joint.
      Arthroscopic decompression of the cyst was performed through a juxtaglenoid
      capsulotomy which was left open. Neurological function recovered completely.

PMID- 17012435
TI  - Systemic effects of severe trauma on the function and apoptosis of human skeletal
      cells.
AB  - Systemic factors are believed to be pivotal for the development of heterotopic
      ossification in severely-injured patients. In this study, cell cultures of
      putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and
      bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive
      polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum
      from 12 healthy control subjects. The serum from the polytraumatised patients
      significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM
      cells. The activity of alkaline phosphatase in MG-63 and hBM cells was
      significantly decreased when exposed to the serum of the severely-injured
      patient. After three weeks in 3D cell cultures, matrix production and osteogenic
      gene expression of hBM cells were equal in the patient and control groups.
      However, the serum from the polytraumatised patients significantly decreased
      apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p =
      0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of
      osteoprogenitors may be responsible for increased osteogenesis in severely
      injured patients.

PMID- 17012436
TI  - Orientation of the acetabular component. A comparison of five navigation systems
      with conventional surgical technique.
AB  - We compared the orientation of the acetabular component obtained by a
      conventional manual technique with that using five different navigation systems.
      Three surgeons carried out five implantations of an acetabular component with
      each navigation system, as well as manually, using an anatomical model. The
      orientation of the acetabular component, including inclination and anteversion,
      and its position was determined using a co-ordinate measuring machine. The
      variation of the orientation of the acetabular component was higher in the
      conventional group compared with the navigated group. One experienced surgeon
      took significantly less time for the procedure. However, his placement of the
      component was no better than that of the less experienced surgeons. Significantly
      better inclination and anteversion (p < 0.001 for both) were obtained using
      navigation. These parameters were not significantly different between the
      surgeons when using the conventional technique (p = 0.966). The use of computer
      navigation helps a surgeon to orientate the acetabular component with less
      variation regarding inclination and anteversion.

PMID- 17012437
TI  - In-cement technique for revision hip arthroplasty.

PMID- 17012438
TI  - Brief report: The accuracy of parents for the thoughts and feelings of their
      adolescent suffering from chronic fatigue: a preliminary study of empathy.
AB  - OBJECTIVE: This study examined the actual and estimated empathic accuracy (EA) of
      the parents of adolescents with chronic fatigue syndrome (CFS). METHODS: The
      actual EA of both parents (n = 24) was assessed in relation to the thoughts and
      feelings of their child (n = 14) about CFS and about other life events.
      Adolescents were also asked to estimate the parents' EA. RESULTS: For the actual
      EA, both parents were significantly less accurate regarding the adolescent's
      thoughts and feelings about CFS than about other life events. Fathers were just
      as empathically accurate as mothers. For the estimated EA, however, results
      indicated that adolescents perceived their mother to be more empathically
      accurate than their father. Actual EA and estimated EA about CFS were negatively
      correlated for fathers, not for mothers. CONCLUSIONS: Results are discussed in
      terms of the importance of assessing EA in relation to other dimensions of
      empathic understanding and distress in the observer.

PMID- 17012439
TI  - Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid
      arthritis. A systematic review.
AB  - OBJECTIVE: To estimate the proportion of rheumatoid arthritis (RA) patients on
      anti-tumour necrosis factor (anti-TNF) who require dose escalation. METHODS:
      Systematic review of the scientific literature. Infliximab, etanercept and
      adalimumab studies in RA were considered. Primary outcome was the proportion of
      patients requiring dose escalation. American College Rheumatology (ACR) and
      Disease activity score (DAS) responses post-escalation were assessed when
      available. RESULTS: From 1801 references, 16 studies with 8510 patients were
      included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty
      four per cent of the infliximab patients experienced dose increase and 8.3%,
      frequency increase. The ACR20 response to dose escalation ranged from 27 to 36%
      and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another.
      Of the etanercept patients, 17.5% experienced a dose increase but changes on the
      mean dose were not statistically significant. CONCLUSIONS: Dose escalation is
      common in patients treated with infliximab, and less frequent with etanercept. In
      a proportion of patients, the dose escalation seems effective. The design and
      evidence level of the available studies limit the strength of the conclusions.

PMID- 17012440
TI  - Changes in the prevalence of asthma and allergic diseases among Brazilian
      schoolchildren (13-14 years old): comparison between ISAAC Phases One and Three.
AB  - The present study is aimed to describe the changes in the prevalence of symptoms
      of asthma, rhinitis and eczema among Brazilian adolescents (AD, 13-14 years old)
      between Phases 1 and 3 of the International Study of Asthma and Allergies in
      Childhood (ISAAC). The prevalence of self-reported symptoms of asthma, rhinitis
      and eczema in AD from five Brazilian cities (Curitiba, Porto Alegre, Recife,
      Salvador and Sao Paulo), obtained during ISAAC Phase 1 (n = 15 419) and Phase 3
      (n = 15 684), was compared to determine the trend of prevalence in a 7-year
      interval. There was a trend to reduction in the current prevalence of wheezing
      and increasing of nocturnal cough when averaging figures from the five cities.
      The prevalence of wheezing in the last 12 months was 27.7 vs. 19.9% (p < 0.01);
      asthma ever 14.9 vs. 14.7% (p > 0.05); severe episode of wheezing 5.2 vs. 5.2%;
      nocturnal cough 32.6 vs. 34.9% (p < 0.01); exercise wheezing 23.6 vs. 23.0% (p >
      0.05) and awake with wheezing 11.8 vs. 11.2% (p > 0.05). Similar things were
      observed with the prevalence of current symptoms of rhinitis and eczema. In
      Brazil, there was a small but significant mean decrease in the prevalence of two
      asthma-related symptoms, wheezing and nocturnal cough, though this trend was not
      consistent in the surveyed cities. The prevalence of asthma symptoms in Brazil,
      despite its mean trend to a decrease, is still one of the highest in Latin
      America.

PMID- 17012441
TI  - Preventing eclampsia: magnesium sulfate regimens revisited.

PMID- 17012442
TI  - Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women
      with gestational hypertension.
AB  - OBJECTIVE: To describe the incidence of eclampsia in women with mild gestational
      hypertension when only women with severe gestational hypertension are given
      magnesium sulfate prophylaxis. METHODS: This is a prospective 4(1/2)-year
      observational study. Those women who met our criteria for severe gestational
      hypertension received intravenous magnesium sulfate prophylaxis, and women with
      nonsevere hypertension did not. Data were collected at delivery to ascertain the
      incidence of eclampsia and maternal and neonatal morbidity. RESULTS: A total of
      72,004 women were delivered during the study period, 6,431 had gestational
      hypertension, 3,935 met the criteria for severe disease and were given magnesium
      sulfate prophylaxis, 2,496 women with nonsevere hypertension were not treated.
      Eighty-seven women developed eclampsia, for an overall incidence of 1 in 828
      deliveries, a 50% increase when compared with 5 preceding years where all women
      with gestational hypertension were given magnesium sulfate prophylaxis. Of the
      2,496 women with nonsevere hypertension who were not treated, 27 had eclampsia (1
      in 92). Women with eclampsia were more likely to require general anesthesia for
      cesarean delivery compared with hypertensive women without eclampsia (23% versus
      4%, P < .001), but they had no additional morbidity. Infants of eclamptic mothers
      had more adverse outcomes than those without convulsions (12% versus 1%, P <
      .04). CONCLUSION: Selective magnesium sulfate prophylaxis results in an increased
      overall incidence of eclampsia because of more seizures in women with nonsevere
      gestational hypertension who are not given magnesium sulfate prophylaxis. LEVEL
      OF EVIDENCE: II-3.

PMID- 17012443
TI  - Abbreviated postpartum magnesium sulfate therapy for women with mild
      preeclampsia: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether women receiving 12-hour and 24-hour postpartum
      magnesium sulfate (MgSO4) therapy for mild preeclampsia have differing clinical
      courses. METHODS: Consenting women with suspected mild preeclampsia were randomly
      assigned to 12 hours or 24 hours of MgSO4 postpartum therapy. Treatment was
      continued after the assigned time period if there was evidence of severe
      preeclampsia. The frequency of progression to severe disease and other outcomes
      were compared between study groups using the Fisher exact, chi2, and Student t
      tests where appropriate. RESULTS: Between January 2001 and August 2004, 200 women
      were enrolled. The 12-hour and 24-hour groups were similar in age, parity,
      delivered gestational age, anesthesia, and mode of delivery, as well as for
      proteinuria and blood pressure. In the 12-hour group, MgSO4 treatment was
      extended in seven women (6.9%) for progression to severe disease versus one
      (1.1%) in the 24-hour group (P = .07). Women who developed severe disease had
      higher blood pressures at the first prenatal visit (140/78 versus 122/69, P < or
      = .02 for systolic and diastolic pressures), at the time of randomization (152/88
      versus 135/78, P < or = .03 for systolic and diastolic pressures), and were more
      likely to have insulin-requiring diabetes (27.3% versus 4.4%, P = .03). No 12
      hour patients required treatment beyond 24 hours postpartum. There were no
      seizures, MgSO4 toxicity, or intolerance in either group. CONCLUSION: Twelve
      hours of postpartum MgSO4 therapy for mild preeclampsia is associated with
      infrequent disease progression and a clinical course similar to that with 24-hour
      therapy. Patients with chronic hypertension and insulin-requiring diabetes are at
      risk for progression to severe disease postpartum. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT00344058 LEVEL OF EVIDENCE: I.

PMID- 17012444
TI  - Trends in perinatal regionalization and the role of managed care.
AB  - OBJECTIVE: To describe trends in regionalization of perinatal care and identify
      factors that predict the extent of regionalization. METHODS: Data were drawn for
      four states for every year between 1989 and 1998. Panel data models estimated the
      effect of managed care enrollment on site of delivery for low, very low, and
      extremely low birth weight neonates. RESULTS: Strong evidence for regionalization
      over time was observed for North Carolina and Illinois, with little change in
      site of delivery in Washington. A shift from level III to level II hospitals was
      observed for low and very low birth weight neonates in California. Although
      managed care enrollment increased substantially in all four states, managed care
      had no effect on site of delivery; that is, the effect of managed care was near
      zero and not statistically significant in any state. CONCLUSION: Evidence
      supports the delivery of high-risk neonates at tertiary care centers. Despite
      changes in site of delivery, the percentages of very low birth weight neonates
      delivered at level III hospitals were substantially lower than the goal of 90%
      set by Healthy People 2010. Financial pressures introduced by managed care cannot
      be blamed for the failure to meet this goal. LEVEL OF EVIDENCE: II-2.

PMID- 17012445
TI  - Temporal relationship between increased nuchal translucency and enlarged jugular
      lymphatic sac.
AB  - OBJECTIVE: To study the relationship between the volume of the jugular lymphatic
      sacs and nuchal translucency thickness in fetuses with increased nuchal
      translucency with advancing gestation. METHODS: Seventy-four fetuses with a
      nuchal translucency greater than the 95th percentile were examined weekly between
      11 and 17 weeks of gestational age. The fetal neck region was studied by
      ultrasonography, followed by measurement of nuchal translucency and jugular
      lymphatic sacs. The measurements were analyzed using multilevel analysis. In case
      of termination of pregnancy postmortem examination was performed. RESULTS: In 40
      euploid fetuses and 34 aneuploid fetuses, 159 measurements of jugular lymphatic
      sac volume and nuchal translucency thickness were analyzed. The volume of the
      jugular lymphatic sacs and gestational age showed a quadratic relation, which
      differed between euploid and aneuploid fetuses (P < .01). The maximum volumes
      were larger and present longer in fetuses with aneuploidy than in euploid fetuses
      (P < .01). In case of a cardiac anomaly, jugular lymphatic sac volume was larger
      than in cardiac normal fetuses (nonsignificant). Furthermore, the development of
      jugular lymphatic sac volume and increased nuchal translucency were related,
      whereby an increase of the nuchal translucency preceded enlargement of the
      jugular lymphatic sacs (P < .001). In each fetus an increase in jugular lymphatic
      sac volume was followed by a decrease with advancing gestation. The gestational
      age at maximum jugular lymphatic sac volume differed between fetuses, indicating
      a fetus-specific pattern. Nuchal translucency development showed a similar
      pattern. Postmortem examination confirmed distension of the jugular lymphatic
      sacs in all cases. CONCLUSION: Increased nuchal translucency is associated with
      abnormal lymphatic development, in which nuchal translucency enlargement precedes
      enlargement of jugular lymphatic sacs on ultrasound examination. Aneuploid
      fetuses have a more disturbed lymph angiogenesis. LEVEL OF EVIDENCE: III.

PMID- 17012446
TI  - Predictors of urinary incontinence in a prospective cohort of postmenopausal
      women.
AB  - OBJECTIVE: To prospectively assess risk factors associated with occurrence of
      urinary incontinence among postmenopausal women. METHODS: We followed up 1,017
      postmenopausal health maintenance organization enrollees, aged 55 to 75 years,
      for 2 years. The primary outcome measures were any urinary incontinence and
      severe incontinence reported at 12- or 24-month follow-up visits. RESULTS:
      Baseline prevalence of any amount or frequency of urinary incontinence in the
      past year was 66%. Among the 345 women without incontinence at baseline, 65 (19%)
      at 1 year and 66 (19%) at 2 years reported any incontinence. Ninety-two of 672
      (14%) and 96 of 672 (14%) women with incontinence at baseline reported no
      incontinence at years 1 and 2. In an adjusted multiple logistic regression model,
      independent predictors of any incontinence included white race (odds ratio [OR]
      1.7, 95% confidence interval [CI] 1.1-2.6), vaginal estrogen cream (OR 2.0, CI
      1.1-3.7), vaginal dryness (OR 1.6, CI 1.2-2.2), vaginal discharge (OR 1.5, CI 1.0
      2.2), 6 or more lifetime urinary tract infections (OR 1.8, CI 1.2-2.6), and
      diabetic peripheral neuropathy (OR 1.7, CI 1.0-3.1). In adjusted models,
      predictors of severe incontinence were history of hysterectomy (OR 1.8, CI 1.1
      2.7) and any vaginal symptom (OR 1.7, CI 1.0-2.8). CONCLUSION: A substantial
      proportion of incontinence-free postmenopausal women developed urinary
      incontinence during 2 years of follow-up. Because vaginal symptoms are associated
      with urinary incontinence, their relationship with other risk factors, including
      vaginal Escherichia coli colonization and vaginal estrogen cream use, warrant
      additional study. Similarly, diabetic peripheral neuropathy and hysterectomy
      associations suggest areas for future investigation. LEVEL OF EVIDENCE: II-2.

PMID- 17012447
TI  - Fecal and urinary incontinence in primiparous women.
AB  - OBJECTIVE: To prospectively investigate the relationship between anal sphincter
      tears and postpartum fecal and urinary incontinence. METHODS: The Childbirth and
      Pelvic Symptoms study was a prospective cohort study performed by the Pelvic
      Floor Disorders Network to estimate the prevalence of postpartum fecal and
      urinary incontinence in primiparous women: 407 with clinically recognized anal
      sphincter tears during vaginal delivery, 390 without recognized sphincter tears
      (vaginal controls), and 124 delivered by cesarean before labor. Women were
      recruited postpartum while hospitalized and interviewed by telephone 6 weeks and
      6 months postpartum. We assessed fecal and urinary incontinence symptoms using
      the Fecal Incontinence Severity Index and the Medical, Epidemiological, and
      Social Aspects of Aging Questionnaire, respectively. Odds ratios were adjusted
      for age, race, and clinical site. RESULTS: Compared with the vaginal control
      group, women in the sphincter tear cohort reported more fecal incontinence (6
      weeks, 26.6% versus 11.2%; adjusted odds ratio [AOR] 2.8, 95% confidence interval
      [CI] 1.8-4.3; 6 months, 17.0% versus 8.2%; AOR 1.9, 95% CI 1.2-3.2), more fecal
      urgency and flatal incontinence, and greater fecal incontinence severity at both
      times. Urinary incontinence prevalence did not differ between the sphincter tear
      and vaginal control groups. Six months postpartum, 22.9% of women delivered by
      cesarean reported urinary incontinence, whereas 7.6% reported fecal incontinence.
      CONCLUSION: Women with clinically recognized anal sphincter tears are more than
      twice as likely to report postpartum fecal incontinence than women without
      sphincter tears. Cesarean delivery before labor is not entirely protective
      against pelvic floor disorders. LEVEL OF EVIDENCE: II-3.

PMID- 17012448
TI  - Risk of urinary incontinence after childbirth: a 10-year prospective cohort
      study.
AB  - OBJECTIVE: To estimate prospectively the effect of first delivery on subjective
      bladder function and to assess the influence of subsequent deliveries and
      obstetric events METHODS: We performed a prospective, observational cohort study.
      During a 10-week period in 1995, 304 of 309 eligible primiparous women (98%)
      entered the study at the postpartum maternity ward and completed a bladder
      function questionnaire. The 10-year observational period was completed by 246 of
      304 subjects (81%). RESULTS: Prevalence of moderate-severe stress urinary
      incontinence increased from 5 of 304 subjects (2%) at baseline to 27 of 229 (12%)
      at 10 years follow-up (P < .001). Prevalence of moderate-severe urinary urgency
      increased from 0 subjects (0%) at baseline to 31 of 229 (13%) at the 10-year
      follow-up (P < .001). The relative risk (RR) (adjusted for maternal age and
      parity) of moderate to severe urinary incontinence increased significantly 10
      years after first delivery (RR 5.8, 95% confidence interval [CI] 1.2-33.7). At
      multivariable analysis adjusted for age and parity, stress urinary incontinence
      symptoms at 9 months and 5 years follow-up were independently associated with the
      presence of symptoms at 10 years after index delivery (RR 13.3, 95% CI 3.9-33.1
      and RR 14.1, 95% CI 2.5-18.8, respectively). Number of vaginal deliveries or
      other obstetric covariates did not affect the risk of stress urinary incontinence
      or urinary urgency. CONCLUSION: Vaginal delivery is independently associated with
      a significant long-term increase in stress urinary incontinence symptoms, as well
      as urinary urgency, regardless of maternal age or number of deliveries. LEVEL OF
      EVIDENCE: II-2.

PMID- 17012449
TI  - Quantification of levator ani cross-sectional area differences between women with
      and those without prolapse.
AB  - OBJECTIVE: Compare levator ani cross-sectional area as a function of prolapse and
      muscle defect status. METHODS: Thirty women with prolapse and 30 women with
      normal pelvic support were selected from an ongoing case-control study of
      prolapse. For each of the two groups, 10 women were selected from three
      categories of levator defect severity: none, minor, and major identified on
      supine magnetic resonance scans. Using those scans, three-dimensional (3D) models
      of the levator ani muscles were made using a modeling program (3D Slicer), and
      cross-sections of the pubic portion were calculated perpendicular to the muscle
      fiber direction using another program, I-DEAS. An analysis of variance was
      performed. RESULTS: The ventral component of the levator muscle of women with
      major defects had a 36% smaller cross-sectional area, and women with minor
      defects had a 29% smaller cross-sectional area compared with the women with no
      defects (P < .001). In the dorsal component, there were significant differences
      in cross-sectional area according to defect status (P = .03); women with major
      levator defects had the largest cross-sectional area compared with the other
      defect groups. For each defect severity category (none, minor, major), there were
      no significant differences in cross-sectional area between women with and those
      without prolapse. CONCLUSION: Women with visible levator ani defects on magnetic
      resonance imaging had significantly smaller cross-sectional areas in the ventral
      component of the pubic portion of the muscle compared with women with intact
      muscles. Women with major levator ani defects had larger cross-sectional areas in
      the dorsal component than women with minor or no defects. LEVEL OF EVIDENCE: II
      2.

PMID- 17012450
TI  - Fetal injury associated with cesarean delivery.
AB  - OBJECTIVE: To describe the incidence and type of fetal injury identified in women
      undergoing cesarean delivery. METHODS: Between January 1, 1999, and December 31,
      2000, a prospective cohort study of all cesarean deliveries was conducted at 13
      university centers. Information regarding maternal and infant outcomes was
      abstracted directly from hospital charts. RESULTS: A total of 37,110 cesarean
      deliveries were included in the registry, and 418 (1.1%) had an identified fetal
      injury. The most common injury was skin laceration (n = 272, 0.7%). Other
      injuries included cephalohematoma (n = 88), clavicular fracture (n = 11),
      brachial plexus (n = 9), skull fracture (n = 6), and facial nerve palsy (n = 11).
      Among primary cesarean deliveries, deliveries with a failed forceps or vacuum
      attempt had the highest rate of injuries (6.9%). In women with a prior cesarean
      delivery, the highest rate of injury also occurred in the unsuccessful trial of
      forceps or vacuum (1.7%), and the lowest rate occurred in the elective repeat
      cesarean group (0.5%). The type of uterine incision was associated with fetal
      injury, 3.4% "T" or "J" incision, 1.4% for vertical incision, and 1.1% for a low
      transverse (P = .003), as was a skin incision-to-delivery time of 3 minutes or
      less. Fetal injury did not vary in frequency with the type of skin incision,
      preterm delivery, maternal body mass index, or infant birth weight greater than
      4,000 g. CONCLUSION: Fetal injuries complicate 1.1% of cesarean deliveries. The
      frequency of fetal injury at cesarean delivery varies with the indication for
      surgery as well as with the duration of the skin incision-to-delivery interval
      and the type of uterine incision. LEVEL OF EVIDENCE: II-3.

PMID- 17012452
TI  - Resident physicians' competencies and attitudes in delivering a postnatal
      diagnosis of Down syndrome.
AB  - OBJECTIVE: This study responded to the need expressed by physicians and parents
      alike for improved medical information and support to families upon the initial
      diagnosis of Down syndrome at birth. The purpose was to assess obstetrics and
      gynecology and pediatrics residents' cognitive knowledge about Down syndrome and
      comfort in counseling parents with a newborn child with Down syndrome before and
      after intervention (resident viewing and interaction with the educational
      material). METHODS: A team of physicians, parents, and educational specialists
      developed an interactive CD-ROM that asked resident physicians to read and view
      virtual patient-doctor sessions, and provide their own responses to critical
      situations related to Down syndrome diagnoses. The research tested both knowledge
      and attitude change, as well as the effectiveness of an interactive CD-ROM as a
      pedagogical tool. RESULTS: Our effectiveness study yielded positive and
      significant improvement in knowledge and level of comfort changes with both
      obstetrics and gynecology and pediatric physicians in residence at the University
      of Kentucky. Residents also found the technologically based interactive type of
      instruction to be usable and valuable. CONCLUSION: Teaching physicians to impart
      accurate and balanced information about Down syndrome at the initial point of
      diagnosis can be achieved, in part, through training with the CD-ROM. From a
      broader perspective, this effectiveness study suggests the potential applications
      of these communication strategies not only to families who have a child with Down
      syndrome, but also to those with other life-altering disabilities. LEVEL OF
      EVIDENCE: II-3.

PMID- 17012451
TI  - Blood transfusion and cesarean delivery.
AB  - OBJECTIVE: To evaluate risks for intraoperative or postoperative packed red blood
      cell transfusion in women who underwent cesarean delivery. METHODS: This was a 19
      university prospective observational study. All primary cesarean deliveries from
      January 1, 1999, to December 31, 2000, and all repeat cesareans from January 1,
      1999, to December 31, 2002, were included. Trained, certified research nurses
      performed systematic data abstraction. Primary and repeat cesarean deliveries
      were analyzed separately. Univariable analyses were used to inform multivariable
      analyses. RESULTS: A total of 23,486 women underwent primary cesarean delivery,
      of whom 762 (3.2%) were transfused (median 2 units, 25th% to 75th% 2-3 units). A
      total of 33,683 women underwent repeat [corrected] cesarean delivery, and 735
      (2.2%) were transfused (median 2 units, 25th% to 75th% 2-4 units). Among primary
      cesareans, general anesthesia (odds ratio [OR] 4.2, 95% confidence interval [CI]
      3.5-5.0), placenta previa (OR 4.8, CI 3.5-6.5) and severe (hematocrit less than
      25%) preoperative anemia (OR 17.0, CI 12.4-23.3) increased the odds of
      transfusion. Among repeat cesareans, the risk was increased by general anesthesia
      (OR 7.2, CI 5.9-8.7), a history of five or more prior cesareans (OR 7.6, CI 4.0
      14.3), placenta previa (OR 15.9, CI 12.0-21.0), and severe preoperative anemia
      (OR 19.9, CI 14.5-27.2). CONCLUSION: Overall, the risk of transfusion in
      association with cesarean is low. However, both severe preoperative maternal
      anemia and placenta previa are associated with markedly increased risks. The
      former argues for optimizing maternal antenatal iron status to avoid severe
      anemia and the latter for careful perioperative planning when previa complicates
      cesarean. LEVEL OF EVIDENCE: II-2.

PMID- 17012453
TI  - Reliability and validity of self-reported symptoms for predicting vulvodynia.
AB  - OBJECTIVE: To evaluate the reliability and validity of self-reported symptoms to
      predict vulvodynia, compared with examination-based confirmation. METHODS:
      Between August 5, 2004, and December 13, 2004, 1,046 members of the University of
      Michigan Women's Health Registry were surveyed regarding the presence of symptoms
      suggestive of vulvodynia. Diagnoses of vulvodynia and of control status based on
      survey responses were made, and a subset of these respondents was evaluated in
      the office. RESULTS: One thousand forty-six of 1,447 (72.3%) eligible women, aged
      19 to 92 years, completed the survey. Seventy-nine (7.6%) of the survey
      respondents who reported ongoing vulvar pain lasting more than 3 months were
      predicted to have vulvodynia, while women reporting no current pain with
      intercourse and no history of prolonged vulvar pain were predicted to be controls
      (N = 543). Agreement between the history taken at the office and that reported on
      the survey was very good (reliability: Cohen's kappa = 0.86, 95% confidence
      interval 0.73-0.99). Of the 28 women predicted to have vulvodynia who were
      examined in the office, 27 (96.4%) were confirmed to have vulvodynia, and 28 of
      the 34 (82.4%) asymptomatic women examined did not have increased vulvar
      sensitivity (Cohen's kappa = 0.78, 95% confidence interval 0.64-0.92).
      CONCLUSION: Excellent reliability and validity of survey responses for predicting
      vulvodynia were demonstrated. LEVEL OF EVIDENCE: II-2.

PMID- 17012454
TI  - Botulinum toxin type A for chronic pain and pelvic floor spasm in women: a
      randomized controlled trial.
AB  - OBJECTIVE: To estimate whether botulinum toxin type A is more effective than
      placebo at reducing pain and pelvic floor pressure in women with chronic pelvic
      pain and pelvic floor muscle spasm. METHODS: This study was a double-blinded,
      randomized, placebo-controlled trial. All participants presented with chronic
      pelvic pain of more than 2 years duration and evidence of pelvic floor muscle
      spasm. Thirty women had 80 units of botulinum toxin type A injected into the
      pelvic floor muscles, and 30 women received saline. Dysmenorrhea, dyspareunia,
      dyschezia, and nonmenstrual pelvic pain were assessed by visual analog scale
      (VAS) at baseline and then monthly for 6 months. Pelvic floor pressures were
      measured by vaginal manometry. RESULTS: There was significant change from
      baseline in the botulinum toxin type A group for dyspareunia (VAS score 66 versus
      12; chi2 = 25.78, P < .001) and nonmenstrual pelvic pain (VAS score 51 versus 22;
      chi2 = 16.98, P = .009). In the placebo group only dyspareunia was significantly
      reduced from baseline (64 versus 27; chi2 = 2.98, P = .043). There was a
      significant reduction in pelvic floor pressure (centimeters of H2O) in the
      botulinum toxin type A group from baseline (49 versus 32; chi2 = 39.53, P <
      .001), with the placebo group also having lower pelvic floor muscle pressures (44
      versus 39; chi2 = 19.85, P = .003). CONCLUSION: Objective reduction of pelvic
      floor spasm reduces some types of pelvic pain. Botulinum toxin type A reduces
      pressure in the pelvic floor muscles more than placebo. Botulinum toxin type A
      may be a useful agent in women with pelvic floor muscle spasm and chronic pelvic
      pain who do not respond to conservative physical therapy. CLINICAL TRIAL
      REGISTRATION: Australian Clinical Trials Registry, http://www.actr.org.au/,
      ACTRN012605000515695 LEVEL OF EVIDENCE: I.

PMID- 17012455
TI  - Oral medroxyprogesterone acetate and combination oral contraceptives for acute
      uterine bleeding: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy of multidose medroxyprogesterone acetate and a
      multidose monophasic combined oral contraceptive (OC) for hemodynamically stable
      women with nongestational, acute uterine bleeding. METHODS: Hemodynamically
      stable patients with acute uterine bleeding sufficient to justify immediate
      medical or surgical intervention were enrolled in an open-label, randomized trial
      comparing oral medroxyprogesterone acetate 20 mg and a monophasic combination OC
      containing 1 mg norethindrone and 35 mug of ethinyl estradiol, each administered
      three times per day. Doses were reduced after 1 week to 20 mg per day and one
      tablet per day for the next 3 weeks for the medroxyprogesterone acetate and OC
      groups, respectively. Following baseline assessment, patients completed daily
      treatment and symptom logs collected at 14 and 28 days after initiation of
      therapy. RESULTS: Forty patients were randomly assigned, 20 in each group; 33
      were evaluated at the 14-day visit. Emergency surgical procedures were avoided in
      100% of those women taking medroxyprogesterone acetate and 95% of the OC group.
      Cessation of bleeding had occurred in 88% of the OC group and 76% of those
      receiving medroxyprogesterone acetate, with a median time to bleeding cessation
      of 3 days for both groups. Compliance with therapy was higher in the
      medroxyprogesterone acetate group than the OC group, but there was no overall
      difference in the incidence of treatment-related nausea and bloating. CONCLUSION:
      This randomized trial is limited by sample size but suggests that both regimens
      may be effective and reasonably well tolerated. CLINICAL TRIAL REGISTRATION:
      Current Clinical Trials (clinicaltrials.gov, www.clinicaltrials.gov) Identifier:
      NCT00350480 LEVEL OF EVIDENCE: II-1.

PMID- 17012456
TI  - Annual costs associated with diagnosis of uterine leiomyomata.
AB  - OBJECTIVE: To describe the annual care, direct health care, and indirect work
      loss costs for women with a diagnosis of uterine leiomyomata. METHODS: We
      examined data from an employer claims database of 1.2 million beneficiaries (1999
      to 2003). Analysis was restricted to women with at least 12 months of continuous
      coverage and ages 18 to 64 years with at least one diagnosis of leiomyomata
      (International Classification of Diseases, 9th Revision, 218.xx, 654.1x). We
      selected a comparison group of women without a leiomyoma diagnosis using a 1:1
      match on age, employment, region, health plan type, and length of enrollment. We
      compared resource use, disability claims, and excess costs in the year after the
      index diagnosis. RESULTS: The average age of women diagnosed with leiomyomata in
      this study was 43.7 years. Women with leiomyomata (N = 5,122) had more clinic
      visits (relative risk [RR] 1.2, 95% confidence interval [CI] 1.2-1.2), diagnostic
      tests (RR 3.1, 95% CI 2.9-3.2), and procedures (RR 34.6, 95% CI 25.8-46.5) than
      controls (N = 5,122). Within 1 year of the diagnosis of leiomyomata, 42% of women
      had a complete blood count, 66% had pelvic imaging, and 30% had surgery (68% of
      surgical procedures involved hysterectomy). Women with leiomyomata were 3-fold
      more likely to have disability claims (RR 3.1, 95% CI 2.7-3.6). Estimated average
      annual excess cost for each woman with leiomyomata (adjusted for confounders) was
      Dollars 4,624 (Dollars 771 in work loss costs). Total costs for women with
      leiomyomata were 2.6 times greater than for controls. CONCLUSION: Diagnosed
      uterine leiomyomata are associated with increased resource use and with
      substantially higher health care and work loss costs. LEVEL OF EVIDENCE: II-3.

PMID- 17012457
TI  - Effects of lifetime exercise on the outcome of in vitro fertilization.
AB  - OBJECTIVE: To estimate whether exercise before the first cycle of in vitro
      fertilization (IVF) affects cycle outcomes. METHODS: A total of 2,232 patients
      were prospectively enrolled before undergoing their first cycle of IVF for the
      treatment of infertility from 1994-2003 at three IVF clinics in the greater
      Boston area. The primary IVF outcomes of interest included successful live birth
      and four points of cycle failure: cycle cancellation, failed fertilization,
      implantation failure, and pregnancy loss. Unconditional logistic regression
      adjusting for observed confounders was used to quantify the relation between self
      reported exercise and cycle outcome. RESULTS: In general, women who reported
      regular exercise were no more likely to have a live birth compared with those
      women who did not report exercise (odds ratio [OR] 0.8, 95% confidence interval
      [CI] 0.7-1.0; P = .07). Women who reported exercising 4 hours or more per week
      for 1-9 years were 40% less likely to have a live birth (OR 0.6, CI 0.4-0.8) and
      were almost three times more likely to experience cycle cancellation (OR 2.8, CI
      1.5-5.3) and twice as likely to have an implantation failure (OR 2.0, CI 1.4-3.1)
      or pregnancy loss (OR 2.0, CI 1.2-3.4) than women who did not report exercise. In
      general, women who participated in cardiovascular exercise had a 30% lower chance
      of successful live birth (OR 0.7, CI 0.6-0.9) than women who reported no
      exercise. CONCLUSION: Regular exercise before in vitro fertilization may
      negatively affect outcomes, especially in women who exercised 4 or more hours per
      week for 1-9 years and those who participated in cardiovascular exercise. LEVEL
      OF EVIDENCE: II-2.

PMID- 17012458
TI  - Isolation of herpes simplex virus from the genital tract during symptomatic
      recurrence on the buttocks.
AB  - OBJECTIVE: To estimate the frequency of isolation of herpes simplex virus (HSV)
      from the genital tract when recurrent herpes lesions were present on the
      buttocks. METHODS: Data were extracted from a prospectively observed cohort
      attending a research clinic for genital herpes infections between 1975 and 2001.
      All patients with a documented herpes lesion on the buttocks, upper thigh or
      gluteal cleft ("buttock recurrence") and concomitant viral cultures from genital
      sites including the perianal region were eligible. RESULTS: We reviewed records
      of 237 subjects, 151 women and 86 men, with a total of 572 buttock recurrences.
      Of the 1,592 days with genital culture information during a buttock recurrence,
      participants had concurrent genital lesions on 311 (20%, 95% confidence interval
      [CI] 14-27%) of these days. Overall, HSV was isolated from the genital region on
      12% (95% CI 8-17%) of days during a buttock recurrence. In the absence of genital
      lesions, HSV was isolated from the genital area on 7% (95% CI 4%-11%) of days
      during a buttock recurrence and, among women, from the vulvar or cervical sites
      on 1% of days. CONCLUSION: Viral shedding of herpes simplex virus from the
      genital area is a relatively common occurrence during a buttock recurrence of
      genital herpes, even without concurrent genital lesions, reflecting perhaps
      reactivation from concomitant regions of the sacral neural ganglia. Patients with
      buttock herpes recurrences should be instructed about the risk of genital
      shedding during such recurrences. LEVEL OF EVIDENCE: II-2.

PMID- 17012459
TI  - Relationship of pregnancy to human papillomavirus among human immunodeficiency
      virus-infected women.
AB  - OBJECTIVE: Because parity is a reported risk factor for cervical cancer, we
      sought to estimate the effects of pregnancy on the prevalence, incident
      detection, and copy number of human papillomavirus (HPV) among human
      immunodeficiency virus (HIV)-infected women, patients at high risk for cervical
      cancer. METHODS: Human immunodeficiency virus-infected women who had a pregnancy
      in the Women's Interagency HIV Study (n = 178) and the Women and Infants
      Transmission Study (n = 450) underwent serial type-specific HPV DNA testing using
      MY09/MY11 polymerase chain reaction. During pregnancy and during the prepregnancy
      and postpregnancy periods, we assessed HPV prevalence, incident detection, and
      HPV copy number (estimated using hybridization signal strength) of both oncogenic
      and nononcogenic HPV. All binary-regression analyses incorporated generalized
      estimating equations to address the repeated observations of the same women over
      time, and were further adjusted for parity, gestational age, smoking,
      antiretroviral use, number of lifetime sexual partners, and oral contraceptive
      use. RESULTS: The prevalence and copy number of oncogenic and nononcogenic HPV
      did not significantly differ between pregnancy and either the prepregnancy or
      postpregnancy periods. Incident HPV detection was significantly lower for both
      oncogenic and nononcogenic HPV during pregnancy compared with the postpregnancy
      period (relative risk 0.534, 95% confidence interval 0.390-0.732, P < .001 and
      relative risk 0.577, 95% confidence interval 0.428-0.779, P < .001,
      respectively), but not compared with the prepregnancy period CONCLUSION: Among
      HIV-infected women, the incident detection of HPV is lower during pregnancy
      compared with postpregnancy, while prevalence and copy number do no differ
      between pregnancy and either prepregnancy or postpregnancy. LEVEL OF EVIDENCE: II
      3.

PMID- 17012460
TI  - Obesity prevention and treatment practices of U.S. obstetrician-gynecologists.
AB  - OBJECTIVE: To describe obesity prevention and treatment practices of U.S.
      obstetrician-gynecologists. METHODS: A cross-sectional survey was mailed to 1,806
      practicing members of the American College of Obstetricians and Gynecologists
      (ACOG) in February-April 2005. RESULTS: Of the 900 respondents who returned
      questionnaires, 82% reported using body mass index (BMI) to assess obesity; 80%
      reported counseling patients about weight control and 84% about physical activity
      "most of the time" or "often." Most reported counseling patients about diet; the
      most frequently recommended dietary strategies were changing eating patterns,
      limiting intake of specific foods, and controlling portion size. About 27%
      reported referring their patients for behavioral therapy "most of the time" or
      "often," and 35% reported ever prescribing weight loss medications to obese
      patients. More than 85% counseled patients about pregnancy weight gain, and 64%
      used the patients' prepregnancy BMI to modify their recommendations "most of the
      time" or "often." Respondents who completed their residency after 1996 were more
      likely to use patients' BMI to screen for obesity than those who finished
      earlier. Respondents who believed that they could help their patients lose weight
      (44%) were more likely to counsel their patients to do so (P < .001). CONCLUSION:
      A majority of obstetrician-gynecologists appear to use BMI to screen for obesity
      and to counsel their patients about weight control, diet, and physical activity.
      Many, however, do not prescribe weight loss medications or refer patients to
      behavioral weight loss therapy. Obstetrician-gynecologists who believe they can
      help patients lose weight are more likely to follow recommendations for the
      treatment of obesity. LEVEL OF EVIDENCE: III.

PMID- 17012461
TI  - Activation of nitric oxide synthesis in human endothelial cells using nomegestrol
      acetate.
AB  - OBJECTIVE: Recent clinical trials indicate that synthetic progestins may be
      unexpectedly relevant for the development of cardiovascular disease. The aim of
      this study was to establish whether nomegestrol acetate induces signaling events
      in human endothelial cells that differ from those of other progestins, such as
      natural progesterone or medroxyprogesterone acetate. METHODS: We used human
      endothelial cells to study the action of nomegestrol acetate (either alone or in
      the presence of estradiol [E2]) on the synthesis of nitric oxide (NO) and on the
      activity or expression of endothelial nitric oxide synthase (eNOS). We compared
      the effects of nomegestrol acetate with those of progesterone or
      medroxyprogesterone acetate. In addition, we characterized the signaling events
      recruited by these compounds. RESULTS: Progesterone and nomegestrol acetate
      increase NO synthesis by transcriptional and nontranscriptional mechanisms,
      whereas medroxyprogesterone acetate lacks such effects. When used together with
      physiological E2 concentrations, progesterone and nomegestrol acetate do not
      interfere with (or even enhance) E2 effects, whereas medroxyprogesterone acetate
      impairs E2 signaling. A marked difference in the recruitment of mitogen-activated
      protein kinase and phosphatidylinositol-3 kinase explains the divergent effects
      of the three gestagens. CONCLUSION: Our findings show significant differences in
      the signal transduction pathways recruited by progesterone, nomegestrol acetate,
      and medroxyprogesterone acetate in human endothelial cells that may have relevant
      clinical implications.

PMID- 17012462
TI  - Quality assessment of reviewers' reports using a simple instrument.
AB  - OBJECTIVE: To validate and test a simple instrument for assessing the quality of
      a review. METHODS: In this prospective observational study, the quality of 247
      reviews of 119 original articles submitted to the Dutch Journal of Medicine was
      assessed using a 5-point scale that has been used for years by Obstetrics &
      Gynecology. Each review was assessed by three editors of the journal.
      Intraobserver variability, calculated as an intraclass correlation coefficient,
      was assessed by having the same editors rate 76 reviews for a second time.
      Validation of the scale was done in two ways. First, editors of three other
      medical journals were asked to rate the 247 reviews using the same 5-point scale.
      Second, all reviews were sent to the authors of the article with a questionnaire
      consisting of 12 yes-or-no questions and one question asking for an overall score
      for the review. RESULTS: The interobserver intraclass correlation coefficient for
      the three editors was 0.62 (95% confidence interval 0.50-0.71) for the first
      assessment of 247 reviews. For the second assessment of 76 reviews, the
      interobserver intraclass correlation coefficient was 0.62 (0.45-0.74). The
      intraobserver intraclass correlation coefficient for each of the internal editors
      ranged from 0.66 to 0.88. The interobserver intraclass correlation coefficient
      for the external editors was 0.60 (0.51-0.68). The interobserver intraclass
      correlation coefficient for all six editors was 0.62 (0.55-0.68). The authors'
      response rate to the questionnaires was 83%. A significant correlation was found
      between the mean total editorial quality assessment and the overall score of the
      authors (intraclass correlation coefficient 0.28, 0.14-0.41). CONCLUSION: This 5
      point scale proved to be a simple, reliable, and valid instrument enabling
      editors to assess the quality of reviews. A significant correlation was found
      between mean editorial quality assessment and the quality as determined by
      authors. LEVEL OF EVIDENCE: III.

PMID- 17012463
TI  - Magnesium sulfate tocolysis: time to quit.
AB  - Intravenous magnesium sulfate tocolysis remains a North American anomaly. This
      therapy rose to prominence based on poor science and the recommendations of
      authorities. However, a Cochrane systematic review concluded that magnesium
      sulfate is ineffective as a tocolytic. The review found no benefit in preventing
      preterm or very preterm birth. Moreover, the risk of total pediatric mortality
      was significantly higher for infants exposed to magnesium sulfate (relative risk
      2.8; 95% confidence interval 1.2-6.6). Given its lack of benefit, possible harms,
      and expense, magnesium sulfate should not be used for tocolysis. Any further use
      of magnesium sulfate for tocolysis should be restricted to formal clinical trials
      with approval by an institutional review board and signed informed consent for
      participants. Should tocolysis be desired, calcium channel blockers, such as
      nifedipine, seem preferable.

PMID- 17012464
TI  - Assessment of new technology in the treatment of idiopathic menorrhagia and
      uterine leiomyomata.
AB  - New technologies available for the treatment of idiopathic menorrhagia include
      five global endometrial ablation devices that use differing ablative methods,
      including thermal balloon, circulated hot fluid, cryotherapy, radiofrequency
      electrosurgery, and microwave energy. All have been compared with rollerball
      endometrial ablation by way of randomized clinical trials and are associated with
      high patient satisfaction rates, regardless of method, but a wide range of
      amenorrhea rates (13.9-55.3%). They are associated with low complication rates
      when performed by well-trained physicians following protocols in Food and Drug
      Administration trials. Some serious complications have been reported
      subsequently. Strict adherence to patient selection criteria and manufacturer
      protocols is strongly recommended. New technologies for the treatment of uterine
      leiomyomata include uterine artery embolization, magnetic resonance-guided
      focused ultrasonography, laparoscopic uterine artery occlusion, and cryomyolysis.
      There is sound evidence for shorter hospital stay, quicker return to work, and a
      similar major complication rate compared with hysterectomy. Uterine artery
      embolization appears to be effective for up to 5 years in reducing bulk symptoms
      and menorrhagia associated with leiomyomata. The chance of reoperation for
      leiomyoma-related symptoms within 5 years is 20-29%. Women who wish to become
      pregnant should be cautioned about potential complications during pregnancy.
      There is insufficient evidence to recommend uterine artery embolization in
      postmenopausal women. With regard to magnetic resonance-guided focused
      ultrasonography, cryomyolysis, and laparoscopic uterine artery occlusion,
      although the initial symptom reduction outcomes have been reported as favorable,
      more data are needed to better understand the durability of these results.

PMID- 17012465
TI  - Placental abruption.
AB  - Placental abruption complicates about 1% of pregnancies and is a leading cause of
      vaginal bleeding in the latter half of pregnancy. It is also an important cause
      of perinatal mortality and morbidity. The maternal effect of abruption depends
      primarily on its severity, whereas its effect on the fetus is determined both by
      its severity and the gestational age at which it occurs. Risk factors for
      abruption include prior abruption, smoking, trauma, cocaine use, multifetal
      gestation, hypertension, preeclampsia, thrombophilias, advanced maternal age,
      preterm premature rupture of the membranes, intrauterine infections, and
      hydramnios. Abruption involving more than 50% of the placenta is frequently
      associated with fetal death. The diagnosis of abruption is a clinical one, and
      ultrasonography and the Kleihauer-Betke test are of limited value. The management
      of abruption should be individualized on a case-by-case basis depending on the
      severity of the abruption and the gestational age at which it occurs. In cases
      where fetal demise has occurred, vaginal delivery is preferable. Disseminated
      intravascular coagulopathy should be managed aggressively. When abruption occurs
      at or near term and maternal and fetal status are reassuring, conservative
      management with the goal of vaginal delivery may be reasonable. However, in the
      presence of fetal or maternal compromise, prompt delivery by cesarean is often
      indicated. Similarly, abruption at extremely preterm gestations may be managed
      conservatively in selected stable cases, with close monitoring and rapid delivery
      should deterioration occur. Most cases of placental abruption cannot be predicted
      or prevented. However, in some cases, maternal and infant outcomes can be
      optimized through attention to the risks and benefits of conservative management,
      ongoing evaluation of fetal and maternal well-being, and through expeditious
      delivery where appropriate.

PMID- 17012466
TI  - An unusual cause of adolescent dysmenorrhea.

PMID- 17012481
TI  - Rate of pathology from atypical glandular cell pap tests classified by the
      Bethesda 2001 nomenclature.

PMID- 17012482
TI  - ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician
      Gynecologists Number 76, October 2006: postpartum hemorrhage.
AB  - Severe bleeding is the single most significant cause of maternal death world
      wide. More than half of all maternal deaths occur within 24 hours of delivery,
      most commonly from excessive bleeding. It is estimated that worldwide, 140,000
      women die of postpartum hemorrhage each year-one every 4 minutes (1). In addition
      to death, serious morbidity may follow postpartum hemorrhage. Sequelae include
      adult respiratory distress syndrome, coagulopathy, shock, loss of fertility, and
      pituitary necrosis (Sheehan syndrome). Although many risk factors have been
      associated with postpartum hemorrhage, it often occurs without warning. All
      obstetric units and practitioners must have the facilities, personnel, and
      equipment in place to manage this emergency properly. Clinical drills to enhance
      the management of maternal hemorrhage have been recommended by the Joint
      Commission on Accreditation of Healthcare Organizations (2). The purpose of this
      bulletin is to review the etiology, evaluation, and management of postpartum
      hemorrhage.

PMID- 17012483
TI  - ACOG Committee Opinion: Number 345, October 2006: vulvodynia.
AB  - Vulvodynia is a complex disorder that can be difficult to treat. It is described
      by most patients as burning, stinging, irritation, or rawness. Many treatment
      options have been used, including vulvar care measures, medication, biofeed
      training, physical therapy, dietary, modifications, sexual counseling, surgery. A
      cotton swab test is used to distinguish generalized disease from localized
      disease. No one treatment is effective for all patients. A number of measures can
      be taken to prevent irritation, and several medications can be used to treat the
      condition.

PMID- 17012484
TI  - ACOG Committee Opinion Number 346, October 2006: amnioninfusion does not prevent
      meconium aspiration syndrome.
AB  - Amnioinfusion has been advocated as a technique to reduce the incidence of
      meconium aspiration and to improve neonatal outcome. However, a large proportion
      of women with meconium-stained amniotic fluid have infants who have taken in
      meconium within the trachea or bronchioles before meconium passage has been noted
      and before amnioinfusion can be performed by the obstetrician; meconium passage
      may predate labor. Based on current literature, routine prophylactic
      amnioinfusion for the dilution of amnioinfusion for meconium-stained amniotic
      fluid should be done only in the setting of additional clinical trials. However,
      amnioinfusion remains a reasonable approach in the treatment of repetitive
      variable decelerations, regardless of amniotic fluid meconium status.

PMID- 17012485
TI  - Toward consistent evidence-based pediatric practice: developing a reliable
      process for narrowing variation.

PMID- 17012486
TI  - Back to basics: primary immune deficiencies: windows into the immune system.

PMID- 17012487
TI  - Precocious puberty.

PMID- 17012488
TI  - Focus on diagnosis: the alkaline phosphatase level: nuances of a familiar test.

PMID- 17012489
TI  - Echinacea.

PMID- 17012490
TI  - Index of suspicion.

PMID- 17012491
TI  - Sinusitis.

PMID- 17012492
TI  - Hemolytic-uremic syndrome.

PMID- 17012493
TI  - Interactions of doctors with the pharmaceutical industry.
AB  - OBJECTIVE: To assess the opinions and practice patterns of obstetrician
      gynaecologists on acceptance and use of free drug samples and other incentive
      items from pharmaceutical representatives. METHODS: A questionnaire was mailed in
      March 2003 to 397 members of the American College of Obstetricians and
      Gynecologists who participate in the Collaborative Ambulatory Research Network.
      RESULTS: The response rate was 55%. Most respondents thought it proper to accept
      drug samples (92%), an informational lunch (77%), an anatomical model (75%) or a
      well-paid consultantship (53%) from pharmaceutical representatives. A third (33%)
      of the respondents thought that their own decision to prescribe a drug would
      probably be influenced by accepting drug samples. Respondents were more likely to
      think the average doctor's prescribing would be influenced by acceptance of the
      items than theirs would be (p<0.002). Respondents who distributed drug samples to
      patients indicated doing so because of patients' financial need (94%) and for
      their convenience (76%) and less so as a result of knowledge of the efficacy of
      the sample product (63%). A third (34%) of respondents agreed that interactions
      with industry should be more strictly regulated. CONCLUSION: Obstetrician
      gynaecologists largely indicated that they would act in accordance with what they
      think is proper regarding accepting incentive items from pharmaceutical
      representatives. Although accepting free drug samples was considered to be
      appropriate more often than any other item, samples were most commonly judged to
      be influential on prescribing practices. The widely accepted practice of
      receiving and distributing free drug samples needs to be examined more carefully.

PMID- 17012494
TI  - The need for a clinical ethics service and its goals in a community healthcare
      service centre: a survey.
AB  - OBJECTIVES: To (1) assess whether according to healthcare providers, the creation
      of an ethics service responds to a need; (2) assess the importance of an ethics
      service for healthcare providers; (3) determine what ethics services should be
      offered and the preferred formats of delivery; and (4) identify key issues to be
      initially dealt with by the ethics service. DESIGN: A survey of healthcare
      providers in Quebec's Centre Local de Services Communautaires (CLSC), healthcare
      institutions dedicated to community health and social services. FINDINGS: 96
      (95%) respondents agreed that an ethics service was needed, and on average the
      ethics service project was judged to be very important. Preferred formats for
      ethics consultation and education were identified, as well as key concerns such
      as the need of respect for the patient as a person, elder abuse and ethical
      issues in home care. CONCLUSION: This survey is helping in the implementation of
      an ethics service and can guide others in similar healthcare institutions.

PMID- 17012495
TI  - Decisions at the end of life: an empirical study on the involvement, legal
      understanding and ethical views of preregistration house officers.
AB  - OBJECTIVES: To collect information on the involvement, legal understanding and
      ethical views of preregistration house officers (PRHO) regarding end-of-life
      decision making in clinical practice. DESIGN: Structured telephone interviews.
      PARTICIPANTS: 104 PRHO who responded. MAIN OUTCOME MEASURES: Information on the
      frequency and quality of involvement of PRHO in end-of-life decision making,
      their legal understanding and ethical views on do-not-resuscitate (DNR) order and
      withdrawal of treatment. RESULTS: Most PRHO participated in team discussions on
      the withdrawal of treatment (n = 95, 91.3%) or a DNR order (n = 99, 95.2%). Of
      them, 46 (44.2%) participants had themselves discussed the DNR order with
      patients. In all, it was agreed by 84 (80.8%) respondents that it would be
      unethical to make a DNR order on any patient who is competent without consulting
      her or him. With one exception, it was indicated by the participants that
      patients who are competent may refuse tube feeding (n = 103, 99.0%) and 101
      (97.1%) participants thought that patients may refuse intravenous nutrition. The
      withdrawal of artificial ventilation in incompetent patients with serious and
      permanent brain damage was considered to be morally appropriate by 95 (91.3%) and
      97 (93.3%) thought so about the withdrawal of antibiotics. The withdrawal of
      intravenous hydration was considered by 67 (64.4%) to be morally appropriate in
      this case. CONCLUSIONS: PRHO are often involved with end-of-life decision making.
      The results on ethical and legal understanding about the limitations of treatment
      may be interpreted as a positive outcome of the extensive undergraduate teaching
      on this subject. Future empirical studies, by a qualitative method, may provide
      valuable information about the arguments underlying the ethical views of doctors
      on the limitations of different types of medical treatment.

PMID- 17012496
TI  - Killing people: what Kant could have said about suicide and euthanasia but did
      not.
AB  - An agent who takes his own life acts in violation of the moral law, according to
      Kant; suicide, and, by extension, assisted suicide are therefore wrong. By a
      similar argument, and with a few important exceptions, killing is wrong;
      implicitly, then, voluntary euthanasia is also wrong. Kant's conclusions are
      uncompelling and his argument in these matters is undermined on considering other
      areas of his thought. Kant, in forbidding suicide and euthanasia, is conflating
      respect for persons and respect for people, and assuming that, in killing a
      person (either oneself or another), we are thereby undermining personhood. But an
      argument along these lines is faulty according to Kant's own standards. There is
      no reason why Kantians have to accept that self-killing and euthanasia are
      contrary to the moral law. Even if some Kantians adhere to this doctrine, others
      can reject it.

PMID- 17012497
TI  - Formal and effective autonomy in healthcare.
AB  - This essay lays the groundwork for a novel conception of autonomy that may be
      called "effective autonomy"-a conception designed to be genuinely action guiding
      in bioethics. As empirical psychology research on the heuristics and biases
      approach shows, decision making commonly fails to correspond to people's desires
      because of the biases arising from bounded cognition. People who are classified
      as autonomous on contemporary philosophical accounts may fail to be effectively
      autonomous because their decisions are uncoupled from their autonomous desires.
      Accordingly, continuing attempts to value patient autonomy must go beyond
      existing philosophical conceptions of autonomy to consider the background
      conditions of human decision making.

PMID- 17012498
TI  - Mass public health programmes and the obligations of sponsoring and participating
      organisations.
AB  - The obligations of organisations associated with policy formation and
      implementation of international mass public health programmes are explored. Lines
      of responsibility are considered to become unclear because of the large number of
      agencies associated with such programmes. A separation of the relevant
      obligations among the bodies responsible for the formulation (usually an
      international non-governmental organisation) and those responsible for the
      implementation of the policies (usually national bodies) is suggested. The
      continuing oral polio vaccine campaign against poliomyelitis in India is used to
      illustrate the general argument. Although the aim of the programme is legitimate
      and laudable, unnecessary harm is currently being caused to some children as a
      result of elements of the policy and this should be rectified immediately. Such
      mass programmes should take care to ensure that people are not unnecessarily
      sacrificed in the drive to attain the desirable ends of the policy.

PMID- 17012499
TI  - Dealing with ethical problems in the healthcare system in Lithuania: achievements
      and challenges.
AB  - Ethical problems in healthcare in Lithuania are identified, existing mechanisms
      that deal with them are analysed and policy implications are discussed. At least
      three groups of ethical problems exist in the Lithuanian healthcare system:
      problems in the healthcare reform process, in interprofessional interaction and
      in doctor-patient relationships. During the past 15 years, several diverse legal,
      political and administrative mechanisms have been implemented in Lithuania to
      tackle these problems. Despite major achievements, numerous problems persist,
      implying that the focus should be shifted to different mechanisms and
      interventions. It is necessary to broaden the conceptual understanding of ethics
      in healthcare and focus on management ethics to tackle ethical problems in
      Lithuania or in other countries in transition.

PMID- 17012500
TI  - Ethical issues in screening for hearing impairment in newborns in developing
      countries.
AB  - Screening of newborns for permanent congenital or early-onset hearing impairment
      has emerged as an essential component of neonatal care in developed countries,
      following favourable outcomes from early intervention in the critical period for
      optimal speech and language development. Progress towards a similar programme in
      developing countries, where most of the world's children with hearing impairment
      reside, may be impeded by reservations about the available level of support
      services and the possible effect of the prevailing healthcare challenges. Ethical
      justification for the systematic introduction of screening programmes for hearing
      in newborns based on the limitations in current primary prevention strategies,
      lack of credible alternative early-detection strategies and the incentives for
      capacity-building for the requisite support services is examined.

PMID- 17012501
TI  - Developing capacity to protect human research subjects in a post-conflict,
      resource-constrained setting: procedures and prospects.
AB  - The capacity-building strategy used by a US-based research organisation, the
      Pacific Institute for Research and Evaluation (PIRE), to strengthen the system
      for the protection of human research subjects and the infrastructure of its
      international collaborating partner, the University of Liberia, are discussed. To
      conduct the much-needed biomedical and social science-based research-related
      activities in the future, this partnership is expected by PIRE to gradually
      evolve over time to strengthen the capacity of the local investigators and
      administrators of the University of Liberia. Accordingly, a unique opportunity to
      share technology and resources with a post-conflict, resource-constrained country
      is created by this partnership. This capacity-building model to strengthen the
      protection of human subjects in research can also be replicated in similar
      resource-constrained international settings and, accordingly, our experiences and
      limitations are shared in this paper.

PMID- 17012502
TI  - Just another reproductive technology? The ethics of human reproductive cloning as
      an experimental medical procedure.
AB  - Human reproductive cloning (HRC) has not yet resulted in any live births. There
      has been widespread condemnation of the practice in both the scientific world and
      the public sphere, and many countries explicitly outlaw the practice. Concerns
      about the procedure range from uncertainties about its physical safety to
      questions about the psychological well-being of clones. Yet, key aspects such as
      the philosophical implications of harm to future entities and a comparison with
      established reproductive technologies such as in vitro fertilisation (IVF) are
      often overlooked in discussions about HRC. Furthermore, there are people who are
      willing to use the technology. Several scientists have been outspoken in their
      intent to pursue HRC. The importance of concerns about the physical safety of
      children created by HRC and comparisons with concerns about the safety of IVF are
      discussed. A model to be used to determine when it is acceptable to use HRC and
      other new assisted reproductive technologies, balancing reproductive freedom and
      safety concerns, is proposed. Justifications underpinning potential applications
      of HRC are discussed, and it is determined that these are highly analogous to
      rationalisations used to justify IVF treatment. It is concluded that people
      wishing to conceive using HRC should have a prima facie negative right to do so.

PMID- 17012503
TI  - Right of the living dead? Consent to experimental surgery in the event of
      cortical death.
AB  - Ravelingien et al have suggested that early human xenotransplantation trials
      should be carried out on patients who are in a permanent vegetative state (PVS)
      and who have previously granted their consent to the use of their bodies in such
      research in the event of their cortical death. Unfortunately, their philosophical
      defence of this suggestion is unsatisfactory in its current formulation, as it
      equivocates on the key question of the status of patients who are in a PVS. The
      solution proposed by them rests on the idea that it should be up to people
      themselves to determine when they should be treated as dead. Yet the authors
      clearly believe (and state) that patients who are in a PVS are in fact dead.
      Finally, given the public good that their proposal is intended to achieve, the
      moral importance they place on the consent of a person to the use of his or her
      body in research is ultimately only defensible in so far as this consent
      represents the wishes of a living person. It is thus only a gentle caricature of
      their position to suggest that according to their account, consent to
      participation in xenotransplantation research is a "right of the living dead".
      The equivocation by Ravelingien et al on the question of whether these people are
      living or dead means that they avoid confronting the implications of their
      argument. The solution proposed by Ravelingien et al to the problem of how we
      should proceed with xenotransplantation research is therefore not as neat as it
      first seems to be.

PMID- 17012504
TI  - Living patients in a permanent vegetative state as legitimate research subjects.

PMID- 17012505
TI  - Relatives of the living dead.

PMID- 17012506
TI  - Research and patients in a permanent vegetative state.

PMID- 17012507
TI  - Respecting rights ... to death.

PMID- 17012508
TI  - What do patients really want to know in an informed consent procedure? A
      questionnaire-based survey of patients in the Bath area, UK.
AB  - BACKGROUND: Medical decision making is based on patient autonomy and informed
      consent, which is an integral part of medical ethics, risk management and
      clinical governance. Consent to treatment has been extensively discussed, but the
      viewpoint of patients is not well represented. A new consent form was introduced
      by the Department of Health in 2001. AIMS: To determine the information most
      important to patients, to facilitate evidence-based guidelines and to provide a
      valid and reliable consent-procedure-satisfaction questionnaire. METHODS: An
      anonymous quantitative survey was carried out, asking 100 patients 15 questions
      regarding procedures they may need to undergo, using a Visual Analogue Scale to
      test the importance of each question. RESULTS AND DISCUSSION: In total there were
      77 respondents and the mean age was 48.8 (SD 17.63, range 20-82) years. There
      were 52% women and 48% men. Major complications, such as not undergoing the
      procedure, future management and long-term effect on work, all scored a median of
      95%. Least concerns were related to technical details of the procedure and minor
      complications (median 64% and 63%, respectively). All other questions were still
      considered important (median 79-93%). No significant differences were observed
      between sex, age and professional groups, but a significant difference was
      observed between the education groups. Qualifications of the doctor did not
      correlate to any other question. CONCLUSIONS: This questionnaire is proposed as a
      basis for informed consent guidelines to health workers and for measures of
      satisfaction with the consent procedure.

PMID- 17012509
TI  - Ethical theory and medical ethics: a personal perspective.

PMID- 17012510
TI  - Globalisation, the sex industry, and health.

PMID- 17012511
TI  - Characteristics of men who pay for sex: a UK sexual health clinic survey.
AB  - BACKGROUND: Populations surveys in the United Kingdom have documented a doubling
      in the number of men paying for sex over the decade 1990 to 2000. We report the
      prevalence of this behaviour in men attending a sexual health clinic, and
      describe their characteristics. METHODS: Retrospective case note review. RESULTS:
      Of 2665 men completing a standard health screening questionnaire, 10% (267)
      reported paid sex. We reviewed case notes of 258 men. The mean age was 34.7
      years. The majority reported paying women, with 4.3% paying men for sex. Men
      reported paying for sex abroad (51%), locally (40%), or elsewhere in the United
      Kingdom (11%), with only 1.7% paying for sex both in the United Kingdom and
      abroad. The majority (66%) had paid for sex in the previous 12 months, and 27%
      were repeated users of prostitutes. Almost half the men (43%) paid for sex while
      in another relationship. Unprotected vaginal sex was more common in men who had
      paid for sex abroad. None of the men had HIV infection, but 20% had a sexually
      transmitted infection (8% chlamydia, 1.3% gonorrhoea, 7% non-gonococcal
      urethritis, and 1.1% syphilis) CONCLUSION: Routine questions about commercial
      sexual contacts could allow targeted health promotion and harm minimisation for
      this group of men, protecting their partners-both unsuspecting and commercial.

PMID- 17012512
TI  - What is the achievable effectiveness of the India AIDS Initiative intervention
      among female sex workers under target coverage? Model projections from southern
      India.
AB  - BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the
      Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk
      groups such as female and male sex workers and their clients, to limit HIV
      transmission in the general population. OBJECTIVES: To assess the potential
      effectiveness of the Avahan intervention at the level of coverage targeted, in
      different epidemiological settings in India. METHODS: A deterministic
      compartmental model of the transmission dynamics of HIV and two sexually
      transmitted infections, and sensitivity analysis techniques, were used, in
      combination with available behavioural and epidemiological data from Mysore and
      Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic
      sexually transmitted infection (STI) management (STI treatment), periodic
      presumptive treatment of STI (PPT), and condom components of the Avahan
      intervention targeted to female sex workers (FSW). RESULTS: If all components of
      the intervention reach target coverage (that is, PPT, STI treatment and condom
      use), the intervention is expected to prevent 22-35% of all new HIV infections in
      FSW and in the total population over 5 years in a low transmission setting like
      Mysore, and to be half as effective in high transmission settings such as
      Bagalkot. The results were sensitive to small variations in intervention
      coverage. The condom component alone is expected to prevent around 20% of all new
      HIV infections over 5 years in Mysore and around 6% for the STI component alone;
      compared with 7%-14% for the PPT component alone. Multivariate sensitivity
      analyses suggested that interventions may be more effective in settings with low
      FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most
      influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The
      Avahan intervention is expected to be effective. However, to be able to
      demonstrate effectiveness empirically in the different settings, it is important
      to achieve target coverage or higher, which in the case of PPT could take a
      number of years to achieve. These preliminary model predictions need to be
      validated with more detailed mathematical models, as better data on sexual
      behaviour, condom use, STI and HIV trends over time, and intervention coverage
      data accumulate over the course of the programme.

PMID- 17012513
TI  - Pursuing scale and quality in STI interventions with sex workers: initial results
      from Avahan India AIDS Initiative.
AB  - BACKGROUND: Migration, population mobility, and sex work continue to drive
      sexually transmitted epidemics in India. Yet interventions targeting high
      incidence networks are rarely implemented at sufficient scale to have impact.
      India AIDS Initiative (Avahan), funded by the Bill and Melinda Gates Foundation,
      is scaling up interventions with sex workers (SWs) and other high risk
      populations in India's six highest HIV prevalence states. METHODS: Avahan
      resources are channelled through state level partners (SLPs) to local level non
      governmental organisations (NGOs) who organise outreach, community mobilisation,
      and dedicated clinics for SWs. These clinics provide services for sexually
      transmitted infections (STIs) including Condom Promotion, syndromic case
      management, regular check-ups, and treatment of asymptomatic infections. SWs take
      an active role in service delivery. STI capacity building support functions on
      three levels. A central capacity building team developed guidelines and
      standards, trains state level STI coordinators, monitors outcomes, and conducts
      operations research. Standards are documented in an Avahan-wide manual. State
      level STI coordinators train NGO clinic staff and conduct supervision of clinics
      based on these standards and related quality monitoring tools. Clinic and
      outreach staff report on indicators that guide additional capacity building
      inputs. RESULTS: In 2 years, clinics with community outreach for SWs have been
      established in 274 settings covering 77 districts. Mapping and size estimation
      have identified 187,000 SWs. In a subset of four large states covered by six SLPs
      (183,000 estimated SWs, 65 districts), 128,326 (70%) of the SWs have been
      contacted through peer outreach and 74,265 (41%) have attended the clinic at
      least once. A total of 127,630 clinic visits have been reported, an increasing
      proportion for recommended routine check ups. Supervision and monitoring
      facilitate standardisation of services across sites. CONCLUSION: Targeted HIV/STI
      interventions can be brought to scale and standardised given adequate capacity
      building support. Intervention coverage, service utilisation, and quality are key
      parameters that should be monitored and progressively improved with active
      involvement of SWs themselves.

PMID- 17012514
TI  - STI declines among sex workers and clients following outreach, one time
      presumptive treatment, and regular screening of sex workers in the Philippines.
AB  - OBJECTIVES: This intervention linked research aimed to reduce prevalence of
      Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) among female sex
      workers by means of one round of presumptive treatment (PT), and improved
      prevention and screening services. METHODS: A single round of PT (azithromycin 1
      g) was given to all female sex workers reached during a 1 month period of
      enhanced outreach activity. Routine sexually transmitted infection (STI)
      screening services were successfully introduced for two groups of unregistered
      sex workers who work in brothels (BSWs) and on the street (SSWs). No changes were
      made to existing screening methods for registered sex workers (RSWs) or lower
      risk guest relations officers (GROs). Cross sectional prevalence of Ng and Ct was
      measured by PCR on three occasions, and stratified by type of sex work. Ng/Ct
      prevalence was assessed twice in clients of BSWs. RESULTS: Prevalence of Ng
      and/or Ct at baseline, 1 month post-PT, and 7 months post-PT was BSWs: 52%, 27%,
      23%; SSWs: 41%, 25%, 28%; RSWs: 36%, 26%, 34%; GROs: 20%, 6%, 24%, respectively.
      Ng/Ct declines 1 month post-PT were significant for all groups. 6 months later
      prevalence remained low for BSWs (p<0.001), and SSWs (p = 0.05), but had returned
      to pre-intervention levels for the other groups. Prevalence of Ng/Ct among
      clients of BSWs declined from 28% early in the intervention to 15% (p = 0.03) 6
      months later. CONCLUSIONS: In this commercial sex setting, one round of PT had a
      short term impact on Ng/Ct prevalence. Longer term maintenance of STI control
      requires ongoing access to effective preventive and curative services.

PMID- 17012515
TI  - Modelling the cost effectiveness of rapid point of care diagnostic tests for the
      control of HIV and other sexually transmitted infections among female sex
      workers.
AB  - BACKGROUND: In sub-Saharan Africa, gonococcal and chlamydial infections are
      usually managed using the syndromic approach. However, many infections are
      asymptomatic in women, and the syndromic algorithm has poor sensitivity and
      specificity for infections caused by Neisseria gonorrhoeae (Ng) and Chlamydia
      trachomatis (Ct). Because of this, rapid point of care (POC) tests for Ct/Ng
      could improve sexually transmitted infection (STI) management in women. This
      study uses mathematical modelling to estimate the incremental cost effectiveness
      of using POC tests to diagnose Ng/Ct instead of the current syndromic approach
      used by the SIDA2 HIV/STI prevention project for female sex workers in Cotonou,
      Benin. METHODS: A dynamic mathematical model was used with data from Cotonou to
      estimate the HIV impact of the existing SIDA2 project (1995-8), and to project
      how impact would change if POC tests had been used. As observed in test
      evaluations, the POC tests were assumed to have high specificity, but a range of
      sensitivities. The incremental economic cost effectiveness of using POC tests was
      modelled using data on intervention costs and an evaluation of an Ng POC test in
      Cotonou in 2004. All costs were in 2004 US dollars. RESULTS: The model estimated
      the STI treatment aspect of the intervention averted 18 553 Ng/Ct and 359 HIV
      infections over 4 years when the syndromic approach was used. In contrast, if
      Ng/Ct had been diagnosed with a 70-80% sensitive and 95% specific POC test then
      24-31% fewer clinic attenders would have been treated, 40-60% more Ng/Ct and HIV
      infections would have been averted, and the incremental cost effectiveness of
      using them would have been 107-151 dollars per HIV infection averted if the POC
      tests cost 2 dollars and 58-81 dollars if they cost 1 dollar. CONCLUSIONS: POC
      tests can be a cost effective strategy for substantially increasing the impact on
      HIV transmission, and decreasing the degree of inappropriate treatment of STI
      treatment interventions that use syndromic management to diagnose Ng/Ct.

PMID- 17012516
TI  - Assessment and treatment of depression in patients with cardiovascular disease:
      National Heart, Lung, and Blood Institute Working Group Report.
AB  - OBJECTIVE: The National Heart, Lung, and Blood Institute convened an
      interdisciplinary working group of experts to develop recommendations for the
      assessment and treatment of depression in patients with coronary heart disease
      (CHD). METHOD: Consensus of experts. RESULTS: Our current recommendations are
      that the Beck Depression Inventory-I be employed for epidemiological studies of
      depression and CHD, that the Patient Health Questionnaire 2-item version be
      employed for screening for trial eligibility, that the Depression Interview and
      Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial
      inclusion, and that the Hamilton rating scale, which is part of the DISH, be
      employed for both depression symptom reduction and the remission criterion in any
      trial. We further recommend that a randomized controlled trial be undertaken to
      determine whether selective serotonin reuptake inhibitors, psychotherapy, or
      combined treatment can reduce the risk of CHD events and mortality associated
      with depression in CHD patients. CONCLUSIONS: This report summarizes the
      recommendations made by the working group and discusses the rationale for each
      recommendation, the strengths and weaknesses of alternative approaches to
      assessment and treatment, and the implications for future research in this area.

PMID- 17012517
TI  - Phobic anxiety, depression, and risk of ventricular arrhythmias in patients with
      coronary heart disease.
AB  - OBJECTIVE: Findings of an association between phobic anxiety and elevated risks
      of sudden cardiac death suggest that phobic anxiety may be related to increased
      risk of ventricular arrhythmias. The purpose of this study was to examine whether
      phobic anxiety is associated with ventricular arrhythmias in patients with
      documented coronary artery disease (CAD). METHODS: Phobic anxiety level was
      measured using the Crown-Crisp phobic anxiety scale in 940 patients (660 men, 280
      women) hospitalized for diagnostic cardiac catheterization between April 1999 and
      June 2002. Depressive symptomatology was assessed using the Beck Depression
      Inventory. Patients were followed for a median follow-up period of 3 years, and
      the occurrence of ventricular arrhythmias was determined through review of
      medical records. RESULTS: Ventricular arrhythmias occurred in 97 patients and
      were significantly related to higher phobic anxiety after statistical adjustment
      for established medical and demographic determinants of arrhythmias (odds ratio =
      1.40; p = .012). Depressive symptomatology was significantly correlated with
      phobic anxiety (r = 0.44, p < .001) and was also related to ventricular
      arrhythmias (odds ratio = 1.40; p = .006). The composite of depression and phobic
      anxiety predicted ventricular arrhythmias with a larger effect size than either
      depression or phobic anxiety score alone (odds ratio = 1.6, 95% confidence
      interval, 1.2-2.1, p = .002). CONCLUSIONS: Both phobic anxiety and depressive
      symptomatology predict ventricular arrhythmias in patients with CAD and may share
      a common factor predictive of ventricular arrhythmias.

PMID- 17012518
TI  - Diurnal cortisol decline is related to coronary calcification: CARDIA study.
AB  - OBJECTIVE: Chronic stress may be a risk factor for coronary heart disease and is
      associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.
      We tested the hypotheses that two markers of HPA axis dysregulation, elevated
      average level (area under the curve, adjusted for time awake) and diurnal decline
      of salivary cortisol, were associated with presence of coronary calcification
      (CaC). METHOD: Seven hundred eighteen black and white middle-aged adults enrolled
      in an ancillary study of Coronary Artery Risk Development in Young Adults
      provided six salivary cortisol samples throughout one full day and had
      measurements of CaC. RESULTS: The prevalence of any calcification was low, 8.1%
      in the participants of the ancillary study, with white men having the highest
      proportion. Average cortisol did not differentiate groups, means = 2.15 and 2.08.
      Those with any CaC declined approximately 6% per hour in cortisol over the course
      of the day, whereas those with no CaC declined more than 8% per hour (p < .003).
      Those persons with slope scores in the flattest quartile had a greater likelihood
      of any CaC than did those in the remaining quartiles adjusted for sex-race group,
      age, smoking, treatment for diabetes, systolic blood pressure, logged
      triglycerides, average cortisol, and educational attainment (odds ratio = 2.58;
      95% confidence interval = 1.26-5.30). CONCLUSIONS: Our results are consistent
      with the hypothesis that HPA axis dysregulation may affect risk for
      atherosclerosis.

PMID- 17012519
TI  - Bone mineral density, bone turnover, and osteoprotegerin in depressed women with
      and without borderline personality disorder.
AB  - OBJECTIVE: Low bone mineral density has repeatedly been reported in patients with
      major depressive disorder (MDD), and MDD has been discussed as a risk factor for
      the development of osteoporosis. MDD in young adults often occurs in the context
      of borderline personality disorder (BPD), and both MDD and BPD have been
      associated with a dysregulation of the hypothalamic-pituitary-adrenal system and
      subsequent hypercortisolemia. To date, it is unclear whether comorbid BPD in
      depressed patients modulates the extent of bone mass reduction. Therefore, we
      examined bone density, markers of bone turnover, and proinflammatory cytokines in
      depressed patients with and without BPD. Patients with BPD alone and healthy
      women served as comparison groups. METHOD: Twenty-four patients with MDD and 23
      patients with comorbid MDD and BPD were included. Sixteen patients with BPD and
      20 healthy women of similar body mass index served as the comparison group. BMD
      was assessed by means of dual-energy x-ray absorptiometry. Markers of bone
      turnover, endocrine and immune parameters were determined. For data analysis, the
      group of depressed patients without comorbid BPD was divided according to age
      into two groups (younger depressed patients with a mean age of 30 years and older
      patients with a mean age of 42.9 years). RESULTS: BMD at the lumbar spine was
      significantly reduced in a) depressed women with comorbid BPD (mean age, 28.6
      years) and in b) older depressed patients without BPD (mean age, 42.9 years).
      Osteocalcin, a marker of osteoblastic activity, and crosslaps, a marker of bone
      loss, were significantly different between the study groups. Tumor necrosis
      factor-alpha was increased in depressed patients when compared with healthy
      women. Furthermore, TNF-alpha was positively correlated with serum crosslaps, a
      marker for osteoclastic activity. CONCLUSION: Depression is associated with
      reduced bone mass, in particular in patients with comorbid BPD. Possible factors
      contributing to BMD reduction include endocrine and immune alterations associated
      with either MDD or BPD. We conclude from our data that a history of MDD with and
      without comorbid BPD should be considered as a risk factor in clinical assessment
      instruments for the identification of persons prone to osteoporosis.

PMID- 17012520
TI  - Depression and stress reactivity in metastatic breast cancer.
AB  - OBJECTIVE: Cancer-related distress due to the psychological and physical
      challenges of metastatic breast cancer (MBC) may result in symptoms of
      depression, which negatively affects quality and may influence quantity of life.
      This study investigated how depression affects MBC stress reactivity, including
      autonomic (ANS) and hypothalamic-pituitary-adrenal (HPA) axis function. METHOD:
      Forty-five nondepressed and 45 depressed patients with MBC underwent a modified
      Trier Social Stress Test (TSST) while affect, cardiovascular, respiratory, and
      cortisol responses were measured. RESULTS: At study entry, depressed compared
      with nondepressed patients had significantly lower log cortisol waking rise
      levels (p = .005) but no other HPA differences. Positive affect (p = .025) and
      high-frequency heart-rate variability (lnHF) (p = .002) were significantly lower
      at TSST baseline in depressed patients. In response to the TSST, depressed
      patients reported significantly lower positive (p = .050) and greater negative
      affect (p = .037) and had significantly reduced lnHF (p = .031). In secondary
      analyses, at TSST baseline both low-frequency (lnLF) (p = .002) and very-low
      frequency (lnVLF) (p = .0001) heart rate variability were significantly lower in
      the depressed group. In secondary analyses during the TSST, those who were
      depressed had significantly lower lnVLF (p = .008) and did not increase aortic
      impedance reactivity as much as did the nondepressed during the stressor (p =
      .005). CONCLUSION: Depression in patients with MBC was associated with
      alterations in autonomic regulation, particularly reductions in respiratory sinus
      arrhythmia, a measure of cardiac vagal control, at baseline and during the TSST.
      In addition, depression was associated with blunted HPA response to awakening.
      Both MBC groups had relative cortisol hyporesponsiveness to acute stress.

PMID- 17012521
TI  - Medical comorbidity in women and men with bipolar disorders: a population-based
      controlled study.
AB  - OBJECTIVE: Rarely has validated information on chronic medical comorbidity been
      presented for persons with bipolar disorder. To deliver appropriate health
      services, it is important to understand the prevalence of chronic medical
      conditions in this population. This study examines chronic medical comorbidity
      using validated methodology in persons with bipolar disorder. METHODS: This is a
      retrospective study of a 100% sample of administrative claims (1996-2001) from
      Wellmark Blue Cross Blue Shield. Three thousand five hundred fifty-seven subjects
      had bipolar I disorder and did not have claims for schizophrenia or
      schizoaffective disorder. Controls had no documented claims for psychiatric
      conditions. Using validated methodology, inpatient and outpatient claims were
      used to determine prevalence of 44 chronic medical conditions. Odds ratios (ORs)
      were adjusted for age, gender, residence, and nonmental healthcare utilization.
      RESULTS: Persons with bipolar disorder were young (mean age, 38.8 years) and
      significantly more likely to have medical comorbidity, including three or more
      chronic conditions (41% versus 12%, p < .001) compared with controls. Elevated
      ORs were found for conditions spanning all organ systems. Hyperlipidemia,
      lymphoma, and metastatic cancer were the only conditions less likely to occur in
      persons with bipolar disorder. CONCLUSION: Bipolar disorders are associated with
      substantial chronic medical burden. Familiarity with conditions affecting this
      population may assist in programs aimed at providing medical care for the
      chronically mentally ill.

PMID- 17012522
TI  - Ethnicity, perceived discrimination, and vascular reactivity to phenylephrine.
AB  - OBJECTIVES: This study examined relationships among ethnicity, perceived
      discrimination, and vascular reactivity to phenylephrine (PE). METHODS: Seventy
      six white patients and 46 black patients were studied at an inpatient clinical
      research center in response to a bolus intravenous injection of 100 microg PE.
      Self-report questionnaires assessed perceived discrimination. RESULTS: After
      controlling for body surface area, number of cigarettes smoked, and baseline
      blood pressure, black patients had greater vascular reactivity to PE than white
      patients (p = .01). There was also a significant relationship between perceived
      discrimination and diastolic blood pressure responsiveness to PE (p < .05). Path
      analyses revealed that perceived discrimination mediated the relationship between
      ethnicity and diastolic pressor responses. Individuals who perceived more
      discrimination had a larger increase in diastolic blood pressure in response to
      PE. CONCLUSION: These data suggest perceived discrimination is associated with
      increased blood pressure responsiveness to PE.

PMID- 17012523
TI  - Psychosomatic medicine and biodefense preparedness--a new role for the American
      Psychosomatic Society.
AB  - Biodefense preparations in the United States have focused mostly on improving
      biosurveillance and hospital surge capacity in the event of an outbreak or a
      weapons of mass destruction (WMD) event. However, what if an invisible bioweapon
      or dirty bomb was released in a major population center, or if avian flu took
      hold with sustained human to human transmission? Suddenly, we need to combine
      efforts from psychosomatic medicine and general medicine with public health
      practice to triage nonexposed patients with somatic symptoms from those with
      medical sequelae resulting from hazardous exposures. This would better enable the
      limited acute care resources to be directed to those most in need of urgent
      medical care. Furthermore, psychosomatic medicine experts are potentially
      important players in biodefense planning related to risk communication and health
      education strategies in a WMD scenario or outbreak in which individuals must make
      informed choices about their need for immediate medical attention.

PMID- 17012524
TI  - Structural equation modeling for conducting tests of differences in multiple
      means.
AB  - Multivariate methods for analyzing group differences in means on dependent
      variables include multivariate analysis of variance, discriminant analysis, and
      multivariate analysis of factor means. To make appropriate choices among these
      methods, researchers should understand the statistical models underlying them. We
      present these models using path diagrams within a structural equation modeling
      framework. Results for the different methods are presented for an example
      concerning coping with asthma.

PMID- 17012525
TI  - Hostility and urine norepinephrine interact to predict insulin resistance: the VA
      Normative Aging Study.
AB  - OBJECTIVE: Previous research has produced mixed results pertaining to the
      association between hostility and insulin resistance. These inconsistent findings
      may be the result of a lack of studies examining potential moderators of this
      relationship and inconsistent measures of insulin resistance and/or hostility. We
      hypothesized that hostility may interact with circulating norepinephrine (NEPI)
      levels, indexed by 24-hour urine concentrations, to affect insulin resistance.
      METHODS: Six hundred forty-three men (mean age = 63.1 years) free of diabetic
      medications completed the Minnesota Multiphasic Personality Inventory and
      participated in a laboratory assessment. The Cook-Medley Hostility (Ho) and 24
      hour urine NEPI were used to predict insulin resistance defined by the
      homeostatic model assessment (HOMA) index, 2-hour postchallenge glucose (PCGL),
      and insulin levels (PCIL) after controlling for nine common covariates. RESULTS:
      Multiple regression showed that the two-way interaction between Ho and NEPI
      significantly predicted HOMA and PCIL, but not PCGL, after controlling for
      covariates. Simple regression slopes of Ho on HOMA and PCIL were explored and
      indicated that, at higher levels of NEPI, higher Ho was associated with higher
      HOMA (beta = 0.14, p < .05). Ho was not a significant predictor of HOMA at mean
      and lower levels of NEPI. Similar results were obtained for PCIL, but not PCGL.
      Cynicism, but not other subscales of Ho, was similarly related to insulin
      resistance and NEPI. CONCLUSION: Individuals with high stress and high hostility
      were more likely to have insulin resistance. It is important to study moderators
      in the relationship between hostility and insulin resistance.

PMID- 17012526
TI  - Hypertension in older adults and the role of positive emotions.
AB  - OBJECTIVE: Negative emotions have been linked to increases in blood pressure, but
      relations between positive emotion and blood pressure have not been investigated.
      Our aim was to test the hypothesis that high positive emotion would be associated
      with lower blood pressure in older adults. METHODS: A cross-sectional study
      included 2564 Mexican Americans aged 65 or older living in one of five
      southwestern states. Primary measures included blood pressure and positive
      emotion score. Data analyses included descriptive and categorical statistics and
      regression and cumulative logit analysis. RESULTS: The average age was 72.5
      years, 52.8% were women, and 32.8% were on antihypertensive medication. For
      individuals not on antihypertensive medication, increasing positive emotion score
      was significantly associated with lower systolic (b = -0.35, standard error (SE)
      = 0.10) and diastolic (b = -0.56, SE = 0.07) blood pressure after adjusting for
      relevant risk factors; for those on antihypertensive medication, increasing
      positive emotion score was significantly associated with lower diastolic (b = 
      0.46, SE = 0.11) blood pressure, but not systolic blood pressure. Positive
      emotion was significantly associated with a four-level joint blood pressure
      variable. Each one-point increase in positive emotion score was associated with a
      3% and 9% decreased odds of being in a higher blood pressure category for those
      on (odds ratio (OR) = 0.97; 95% confidence interval (CI) = 0.93-1.00) and not on
      (OR = 0.91; 95% CI = 0.89-0.93) antihypertensive medication, respectively.
      CONCLUSIONS: Findings indicate an association between high positive emotion and
      lower blood pressure among older Mexican Americans. Targeting the emotional
      health of older adults might be considered part of nonpharmacologic hypertension
      treatment programs or as part of adjunctive therapy for those on antihypertensive
      medication.

PMID- 17012527
TI  - Effects of naltrexone on repressive coping and disclosure of emotional material:
      a test of the opioid-peptide hypothesis of repression and hypertension.
AB  - OBJECTIVE: The present study was designed to assess the role of endogenous
      opioids in the relationship of hypertension to repressive coping. METHODS: Ten
      hypertensive and 8 normotensive males were given either the opioid antagonist
      naltrexone or placebo in a randomized, double-blind fashion over the course of
      four laboratory sessions. Measures of repression and disclosure were completed
      and blood pressure was assessed during a laboratory stressor protocol. RESULTS:
      Opioid antagonism reduced repression and increased disclosure only in the
      hypertensive group. Also, opioid antagonism increased stress-related systolic
      blood pressure only in the hypertensive group. CONCLUSION: The results support
      the hypothesis that endogenous opioid dysregulation underlies both hypertension
      and repressive phenomena.

PMID- 17012528
TI  - Maternal psychological distress, prenatal cortisol, and fetal weight.
AB  - OBJECTIVE: The objective of this study was to examine the effects of maternal
      psychological distress on estimated fetal weight during midgestation and explore
      the maternal hypothalamic-pituitary axis and sympathoadrenal dysregulation as
      potential risk factors for these effects. METHODS: Fetal ultrasound biometry
      measurements and maternal sociodemographic characteristics, emotional distress
      symptoms, and first morning urine samples were collected during a clinical
      ultrasound examination for a cross-sectional sample of 98 women who were between
      16 and 29 weeks pregnant. Fetal weight was estimated from ultrasound biometry
      measurements; maternal emotional distress was assessed using the daily hassles
      (stress), Center for Epidemiologic Studies-Depression (depression), and State
      Trait Anxiety Inventory (anxiety) scales; and urine samples were assayed for
      cortisol and norepinephrine levels. RESULTS: Correlation analyses revealed that
      both maternal psychological (daily hassles, depression, and anxiety) and
      biochemical (cortisol and norepinephrine) variables were negatively related to
      fetal biometry measurements and estimated fetal weight. A structural equation
      model further revealed that when the independent variance of maternal
      sociodemographic, psychological distress, and biochemistry measures were
      accounted for, prenatal cortisol was the only significant predictor of fetal
      weight. CONCLUSIONS: Women exhibiting psychological distress during pregnancy
      exhibit elevated cortisol levels during midgestation that are in turn related to
      lower fetal weight.

PMID- 17012529
TI  - Onset of spontaneous panic attacks: a prospective study of risk factors.
AB  - OBJECTIVE: Earlier analyses have shown that, among currently well individuals
      with no history of panic attacks, a family history of panic disorder is
      associated with a greater likelihood of panic symptoms after exposure to 35% CO2
      and of ventilatory-response abnormalities during inhalation of 5% CO2. An
      association of those features with a subsequent onset of panic attacks would
      compose additional evidence that they are trait markers for panic disorder.
      METHODS: Subjects who were free of current Axis I disorders other than simple or
      social phobia and who had a first-degree relative with panic disorder (high risk)
      and subjects who had no first-degree relatives with panic disorder or major
      depressive disorder (low-risk) underwent two challenge procedures. The first
      measured anxiety responses to a single breath of 35% CO2, and the second measured
      ventilatory responses to a 3-minute exposure to 5% CO2. After a mean interval of
      4 years, 66 high-risk (48 female; mean age = 23.0 years) and 24 low-risk subjects
      (15 female; mean age = 23.1 years) were questioned by telephone about the
      occurrence of any spontaneous panic attack in the interval. RESULTS: Sixteen
      (23.9%) of the high-risk and one (4.2%) of low-risk subjects had experienced at
      least one spontaneous panic attack; Cox regression analyses revealed a
      significant relationship between abnormal ventilatory responses to 5% CO2 and the
      later onset of panic attacks. Subjective responses to 35% CO2 were not
      predictive. Neuroticism scores were not associated with abnormal ventilatory
      responses to CO2 but were also predictive of later panic attacks. CONCLUSIONS:
      High neuroticism scores and abnormal ventilatory responses to 5% CO2 appear to be
      additive trait markers for panic disorder.

PMID- 17012530
TI  - Selective processing of gastrointestinal symptom-related stimuli in irritable
      bowel syndrome.
AB  - OBJECTIVES: We sought to determine whether irritable bowel syndrome (IBS) was
      associated with attentional bias toward symptom-related cues in IBS patients
      versus healthy controls, using a modified Stroop task to measure selective
      processing of gastrointestinal symptom-related cues. METHODS: Fifteen patients
      with a clinical diagnosis of IBS and 15 healthy controls were recruited into the
      study. All participants attended a single testing session, during which they
      completed a modified Stroop task using gastrointestinal symptom-related and
      neutral control words. RESULTS: Results indicated a significant main effect of
      word type (p = .013), with slower color-naming times for IBS-related compared
      with neutral words, and a significant main effect of exposure (p = .001), with
      slower color-naming times in the unmasked condition compared with the masked
      condition. The group x word type x exposure interaction was significant (p =
      .048). A series of post hoc tests indicated that among patients there was
      significant interference of symptom-related words in the masked condition but not
      in the unmasked condition, whereas among controls, the reverse was true.
      CONCLUSIONS: These results indicate that IBS patients selectively process
      gastrointestinal symptom-related words compared with neutral words when they are
      presented subliminally but not when they are presented supraliminally. In
      contrast, healthy controls demonstrate the opposite pattern. Implications for the
      cognitive mechanisms in IBS, and future research directions, are discussed.

PMID- 17012531
TI  - Evaluation of booklet-based self-management of symptoms in Meniere disease: a
      randomized controlled trial.
AB  - OBJECTIVE: This study examined the effectiveness of booklet-based education in
      vestibular rehabilitation (VR) and symptom control (SC) techniques to manage
      vertigo and dizziness in Meniere disease. METHODS: Participants (n = 360) were
      randomized to a waiting list control group or to receive either a VR or an SC
      self-management booklet. VR involved provoking dizziness in a controlled manner
      by making repeated head movements in order to promote neurological and
      psychological habituation. SC involved using applied relaxation, challenging
      negative beliefs, and lifestyle modification to reduce amplification of dizziness
      by anxiety. Subjective improvement in health, enablement (ability to understand
      and cope with symptoms), and adherence were measured at 3 and 6 months. Symptoms,
      handicap, anxiety and depression, and negative beliefs about symptoms were
      assessed pretreatment and at 3 and 6 months. RESULTS: At 6-month follow-up, 45
      (37.5%) of the VR group and 47 (39.2%) of the SC group reported improvement
      compared with 19 (15.8%) controls; the relative probability of improvement
      compared with controls was 2.37 (95% confidence interval [CI], 1.48-3.80) for VR
      and 2.47 (95% CI, 1.55-3.95) for SC. Both intervention groups reported greater
      enablement than controls (p < .001, d > 0.70). At 3 months, the VR group had
      reduced symptoms, anxiety, handicap, and negative beliefs about dizziness; the SC
      group had reduced handicap; but the control group showed no improvement. Reported
      adherence levels were low and strongly related to outcome. CONCLUSIONS: Self
      management booklets offer an inexpensive and easily disseminated means of helping
      people with Meniere disease to cope with dizziness symptoms.

PMID- 17012532
TI  - Features of hypochondriasis and illness worry in the general population in
      Germany.
AB  - OBJECTIVE: Although hypochondriasis is considered to be of high relevance in the
      healthcare sector, its prevalence in the general population has been investigated
      in few studies. The aims of this study were to estimate prevalence rates of
      hypochondriasis and of subthreshold conditions and to describe their associated
      features such as quality of life and healthcare utilization in a representative
      community sample. METHODS: Analyses of the present study are based on the German
      Health Interview and Examination Survey-Mental Health Supplement (N = 4181,
      representative for the German population from 18-65 years). The assessment
      included interviews for somatic conditions and mental disorders and self-report
      ratings on health-related quality of life, healthcare utilization, disability
      days, and physical activity. RESULTS: Only three cases (0.05%) were identified as
      meeting full criteria of Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV) hypochondriasis. The prevalence rate of the less
      restrictively defined form of hypochondriasis, ("subthreshold hypochondriasis")
      was 0.58% and an additional 2.12% reported having had illness worries for at
      least 6 months but did not meet further hypochondriasis criteria. The two
      subthreshold diagnostic groups provided strong evidence of difference from the
      nonhypochondriac controls: comorbidity with psychiatric and medical disorders and
      healthcare utilization were higher, and quality of life was markedly reduced.
      CONCLUSIONS: The results provide additional support to not only consider "full"
      DSM-IV hypochondriasis, which is a very rare disorder in the general population,
      but also to include less restrictive hypochondriac conditions--associated with a
      clinically relevant degree of psychological and physical impairment--into
      clinical and scientific considerations.

PMID- 17012533
TI  - Weekly alcohol consumption, brain atrophy, and white matter hyperintensities in a
      community-based sample aged 60 to 64 years.
AB  - OBJECTIVE: The objective of this study was to determine the association between
      weekly alcohol consumption and brain atrophy in adults aged 60 to 64 years.
      METHODS: Brain magnetic resonance imaging scans from 385 adults recruited through
      a community survey were analyzed. Automated segmentation and manual tracing
      methods were used to obtain brain subvolumes and automated methods were used to
      obtain quantification and localization of white matter hyperintensities. Visual
      measures of cortical atrophy were obtained as were data on health and lifestyle
      factors. Alcohol consumption was assessed with the Alcohol Use Disorders
      Identification Test. RESULTS: In men, weekly alcohol consumption had a positive
      linear association with ventricular volume and gray matter and a negative linear
      association with white matter. In women, weekly alcohol consumption had a
      nonlinear relationship with cerebrospinal fluid and white matter. Alcohol
      consumption was not associated with white matter hyperintensities, corpus
      callosum size, hippocampal or amygdala volumes in analyses adjusting for
      confounding variables. CONCLUSION: An association between alcohol consumption and
      brain atrophy is evident at the population level. In women, detrimental effects
      of alcohol on the brain appear to occur at lower levels of consumption. It
      remains possible that low levels of alcohol consumption have neuroprotective
      benefits but is clear that high levels of consumption are detrimental.

PMID- 17012534
TI  - Anger management style and hostility among patients with chronic pain: effects on
      symptom-specific physiological reactivity during anger- and sadness-recall
      interviews.
AB  - OBJECTIVES: We examined whether anger-in, anger-out, and hostility predicted
      symptom-specific muscle tension reactivity during anger induction (but not
      sadness induction) among patients with chronic low back pain (CLBP). For patients
      with CLBP, relevant muscles are the lower paraspinals (LPs). Anger-in x hostility
      and anger-out x hostility interactions were tested to determine whether
      particularly reactive groups of patients could be identified with a multivariable
      profile approach. METHODS: Ninety-four patients with CLBP underwent anger recall
      (ARI) and sadness recall (SRI) interviews, whereas LP and trapezius
      electromyography and systolic blood pressure, diastolic blood pressure, and heart
      rate were recorded. They completed anger-in, anger-out, hostility, and trait
      anger measures. RESULTS: Hierarchical regressions were used to test anger-in x
      hostility and anger-out x hostility interactions for physiological changes during
      the ARI and SRI. A significant anger-in x hostility interaction was found for LP
      change during the ARI (but not SRI) such that high anger-in/high hostility
      patients evinced the greatest reactivity. Effects for trapezius reactivity were
      nonsignificant. Significant anger-in x hostility interactions were also found for
      systolic blood pressure and diastolic blood pressure changes during the ARI such
      that high anger-in/low hostility patients showed the smallest changes. The anger
      out x hostility interaction for diastolic blood pressure change during ARI was
      also significant such that high anger-out/low hostility patients showed the
      smallest changes. All effects remained significant with trait anger controlled.
      CONCLUSIONS: A multivariable profile approach may help identify especially
      vulnerable patient groups. Patients with CLBP who tend to suppress anger and are
      cynically hostile may be more likely to experience high levels of muscle tension
      near the site of pain and injury during anger, but not during sadness, than other
      groups.

PMID- 17012535
TI  - Resource loss predicts depression and anxiety among patients treated with an
      implantable cardioverter defibrillator.
AB  - OBJECTIVE: Many patients treated with an implantable cardioverter defibrillator
      (ICD) experience clinically significant depression and anxiety after ICD
      implantation. As ICD use continues to evolve, it is important to understand the
      correlates of depression and anxiety to identify patients at greatest risk of
      poor psychological functioning. Conservation of resources theory, a general
      theory of stress, states that people experience greater stress if they perceive
      that they are losing personal, social, and material resources. We hypothesized
      that perceptions of resource loss would be related to symptoms of depression and
      anxiety after controlling for other known predictors. METHODS: One hundred
      patients treated with an ICD completed standardized depression and anxiety
      questionnaires along with questionnaires assessing social support, physical
      functioning, and resource loss. Clinical variables for patients were obtained
      from prospectively obtained medical records. RESULTS: Over 20% of the sample
      exhibited elevated symptoms of depression and anxiety. Patients' depression
      levels were associated with poor social support, poor physical functioning, a
      history of depression, and a greater length of time since ICD implantation.
      Having experienced one or more clinical ICD shocks was related to depression but
      not anxiety. Higher levels of perceived resource loss were associated with higher
      levels of both depression and anxiety after controlling for all other predictors.
      CONCLUSIONS: Resource loss may help to determine psychological distress after ICD
      implantation. Understanding how resource loss contributes to depression and
      anxiety may help to identify patients at greatest risk of poor psychological
      functioning and may suggest treatment strategies.

PMID- 17012536
TI  - Allostatic load and clinical risk as related to sense of coherence in middle-aged
      women.
AB  - OBJECTIVE: To investigate how physiologic dysregulation, in terms of allostatic
      load and clinical risk, respectively, relates to sense of coherence (SOC) in
      women with no previously diagnosed pathology. METHODS: At baseline, 200 43-year
      old women took part in a standardized medical health examination and completed a
      3-item measure of SOC, which they completed again 6 years later. According to
      data from the medical examination, two different measures of physiologic
      dysregulation were calculated: a) a measure of allostatic load based on
      empirically derived cut points and b) a measure of clinical risk based on
      clinically significant cut points. RESULTS: In line with the initial hypotheses,
      allostatic load was found to predict future SOC, whereas clinical risk did not.
      In addition to baseline SOC and nicotine consumption, allostatic load was
      strongly associated with a weak SOC at the follow-up. CONCLUSIONS: The better
      predictive value of allostatic load to clinical risk indicates that focusing
      solely on clinical risk obscures patterns of physiologic dysregulation that
      influence future SOC.

PMID- 17012537
TI  - The Tetrahymena thermophila phagosome proteome.
AB  - In vertebrates, phagocytosis occurs mainly in specialized cells of the immune
      system and serves as a primary defense against invading pathogens, but it also
      plays a role in clearing apoptotic cells and in tissue remodeling during
      development. In contrast, unicellular eukaryotes, such as the ciliate Tetrahymena
      thermophila, employ phagocytosis to ingest and degrade other microorganisms to
      meet their nutritional needs. To learn more about the protein components of the
      multistep process of phagocytosis, we carried out an analysis of the Tetrahymena
      phagosome proteome. Tetrahymena cells were fed polystyrene beads, which allowed
      for the efficient purification of phagosomes. The protein composition of purified
      phagosomes was then analyzed by multidimensional separation coupled with tandem
      mass spectrometry. A total of 453 peptides were identified that resulted in the
      identification of 73 putative phagosome proteins. Twenty-eight of the proteins
      have been implicated in phagocytosis in other organisms, indicating that key
      aspects of phagocytosis were conserved during evolution. Other identified
      proteins have not previously been associated with phagocytosis, including some of
      unknown function. Live-cell confocal fluorescence imaging of Tetrahymena strains
      expressing green fluorescent protein-tagged versions of four of the identified
      phagosome proteins provided evidence that at least three of the proteins
      (including two with unknown functions) are associated with phagosomes, indicating
      that the bulk of the proteins identified in the analyses are indeed phagosome
      associated.

PMID- 17012539
TI  - The disposition and metabolism of naveglitazar, a peroxisome proliferator
      activated receptor alpha-gamma dual, gamma-dominant agonist in mice, rats, and
      monkeys.
AB  - Naveglitazar [LY519818; benzenepropanoic acid, alpha-methoxy-4-[3-(4
      phenoxyphenoxy)propoxy], (alpha-S)-] is a nonthiozolidinedione peroxisome
      proliferator-activated receptor alpha-gamma dual, gamma-dominant agonist that has
      shown glucose-lowering potential in animal models and in the clinic. Studies have
      been conducted to characterize the disposition, metabolism, and excretion of
      naveglitazar in mice, rats, and monkeys after oral and/or i.v. bolus
      administration. After oral administration of [(14)C]naveglitazar, naveglitazar
      was well absorbed and moderately metabolized in all species evaluated, with total
      recoveries of radioactivity ranging from 90 to 96%. Naveglitazar was the most
      abundant peak observed in circulation at C(max), representing 68 to 81% of the
      total radioactivity in plasma. The most prominent metabolite observed in
      circulation was the R-enantiomer of naveglitazar, LY591026, which is formed via
      enzymatic chiral inversion. para-Hydroxy naveglitazar and the sulfate conjugate
      of para-hydroxy naveglitazar were also observed in circulation in most species,
      especially in the monkey. The metabolic pathways observed include enzymatic
      chiral inversion, aromatic hydroxylation, oxidative dehydrogenation, and/or
      various phase II conjugation pathways. Naveglitazar was highly bound to plasma
      proteins among the species examined (>99%), and binding was independent of
      concentration. Biliary excretion was recognized as the most prominent excretion
      pathway in bile duct-cannulated rats (79 of the 96% recovered), producing an acyl
      glucuronide conjugate of naveglitazar and a sulfate and glucuronide diconjugate
      of para-hydroxy naveglitazar, which were shown to be reversible. The primary
      excretory pathway observed in mice and monkeys was via the feces. In summary,
      naveglitazar was well absorbed, moderately metabolized, and excreted via the
      feces in mice, rats, and monkeys.

PMID- 17012538
TI  - VIB-1 is required for expression of genes necessary for programmed cell death in
      Neurospora crassa.
AB  - Nonself recognition during somatic growth is an essential and ubiquitous
      phenomenon in both prokaryotic and eukaryotic species. In filamentous fungi,
      nonself recognition is also important during vegetative growth. Hyphal fusion
      between genetically dissimilar individuals results in rejection of heterokaryon
      formation and in programmed cell death of the fusion compartment. In filamentous
      fungi, such as Neurospora crassa, nonself recognition and heterokaryon
      incompatibility (HI) are regulated by genetic differences at het loci. In N.
      crassa, mutations at the vib-1 locus suppress nonself recognition and HI mediated
      by genetic differences at het-c/pin-c, mat, and un-24/het-6. vib-1 is a homolog
      of Saccharomyces cerevisiae NDT80, which is a transcriptional activator of genes
      during meiosis. For this study, we determined that vib-1 encodes a nuclear
      protein and showed that VIB-1 localization varies during asexual reproduction and
      during HI. vib-1 is required for the expression of genes involved in nonself
      recognition and HI, including pin-c, tol, and het-6; all of these genes encode
      proteins containing a HET domain. vib-1 is also required for the production of
      downstream effectors associated with HI, including the production of
      extracellular proteases upon carbon and nitrogen starvation. Our data support a
      model in which mechanisms associated with starvation and nonself recognition/HI
      are interconnected. VIB-1 is a major regulator of responses to nitrogen and
      carbon starvation and is essential for the expression of genes involved in
      nonself recognition and death in N. crassa.

PMID- 17012540
TI  - Specificity of aminoacylase III-mediated deacetylation of mercapturic acids.
AB  - Trichloroethylene (TCE) and other halogenated alkenes are known environmental
      contaminants with cytotoxic and nephrotoxic effects, and are potential
      carcinogens. Their metabolism via the mercapturate metabolic pathway was shown to
      lead to their detoxification. The final products of this pathway, mercapturic
      acids or N-acetyl-l-cysteine S-conjugates, are secreted into the lumen in the
      renal proximal tubule. The proximal tubule may also deacetylate mercapturic
      acids, and the resulting cysteine S-conjugates are transformed by cysteine S
      conjugate beta-lyases to nephrotoxic reactive thiols. The specificity and rate of
      mercapturic acid deacetylation may determine the toxicity of certain mercapturic
      acids; however, the exact enzymologic processes involved are not known in detail.
      In the present study we characterized the kinetics of the recently cloned mouse
      aminoacylase III (AAIII) toward a wide spectrum of halogenated mercapturic acids
      and N-acetylated amino acids. In general, the V(max) value of AAIII was
      significantly larger with chlorinated and brominated mercapturic acids, whereas
      fluorination significantly decreased it. The enzyme deacetylated mercapturic
      acids derived from the TCE metabolism including N-acetyl-S-(1,2-dichlorovinyl)-l
      cysteine (NA-1,2-DCVC) and N-acetyl-S-(2,2-dichlorovinyl)-l-cysteine (NA-2,2
      DCVC). Both mercapturic acids induced cytotoxicity in mouse proximal tubule mPCT
      cells expressing AAIII, which was decreased by an inhibitor of beta-lyase,
      aminooxyacetate. The toxic effect of NA-2,2-DCVC was smaller than that of NA-1,2
      DCVC, indicating that factors other than the intracellular activity of AAIII
      mediate the cytotoxicity of these mercapturic acids. Our results indicate that in
      proximal tubule cells, AAIII plays an important role in deacetylating several
      halogenated mercapturic acids, and this process may be involved in their cyto-
      and nephrotoxicity.

PMID- 17012542
TI  - Biotransformation of geldanamycin and 17-allylamino-17-demethoxygeldanamycin by
      human liver microsomes: reductive versus oxidative metabolism and implications.
AB  - Comparative metabolite profiling of geldanamycin and 17-allylamino-17
      demethoxygeldanamycin (17AAG) using human liver microsomes in normoxia and
      hypoxia was conducted to understand their differential metabolic fates.
      Geldanamycin bearing a 17-methoxy group primarily underwent reductive metabolism,
      generating the corresponding hydroquinone under both conditions. The formed
      hydroquinone resists further metabolism and serves as a reservoir. On exposure to
      oxygen, this hydroquinone slowly reverts to geldanamycin. In the presence of
      glutathione, geldanamycin was rapidly converted to 19-glutathionyl geldanamycin
      hydroquinone, suggesting its reactive nature. In contrast, the counterpart
      (17AAG) preferentially remained as its quinone form, which underwent extensive
      oxidative metabolism on both the 17-allylamino sidechain and the ansa ring. Only
      a small amount (<1%) of 19-glutathione conjugate of 17AAG was detected in the
      incubation of 17AAG with glutathione at 37 degrees C for 60 min. To confirm the
      differential nature of quinone-hydroquinone conversion between the two compounds,
      hypoxic incubations with human cytochrome P450 reductase at 37 degrees C and
      direct injection analysis were performed. Approximately 89% of hydroquinone, 5%
      of quinone, and 6% of 17-O-demethylgeldanamycin were observed after 1-min
      incubation of geldanamycin, whereas about 1% of hydroquinone and 99% of quinone
      were found in the 60-min incubation of 17AAG. The results provide direct evidence
      for understanding the 17-substituent effects of these benzoquinone ansamycins on
      their phase I metabolism, reactivity with glutathione, and acute hepatotoxicity.

PMID- 17012543
TI  - Notification that new names and new combinations have appeared in volume 56, part
      7, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 17012541
TI  - Elevated warfarin metabolism in warfarin-resistant roof rats (Rattus rattus) in
      Tokyo.
AB  - Wild roof rats (Rattus rattus) live in proximity to human habitats, and they may
      carry numerous pathogens of infectious diseases. Pest control is important for
      public health, and warfarin is a commonly used rodenticide worldwide. However,
      continual use of warfarin may cause drug resistance in rodents and lead to
      failure of their control, especially in urbanized areas. In warfarin-resistant
      rats, the warfarin level in plasma was significantly lower after oral
      administration than that in the control warfarin-sensitive rats. Warfarin is
      metabolized by cytochrome P450 (P450), and hydroxylation of warfarin by P450
      isoforms was significantly higher in warfarin-resistant rats (2-fold). Western
      blot analysis indicated that the level of CYP3A2 expression in warfarin-resistant
      rats was significantly larger than in warfarin-sensitive rats. The NADPH-P450
      reductase activities in resistant rats were 8-fold higher than those in sensitive
      rats. In vivo, the administration of the P450 potent inhibitor proadifen (SKF
      525A) increased the mortality of warfarin in the warfarin-resistant roof rats. We
      concluded that the mechanism of warfarin resistance in Tokyo roof rats is caused
      by increased clearance of warfarin.

PMID- 17012544
TI  - Phylogenetic evaluation of cyanobacteria preserved as historic herbarium
      exsiccata.
AB  - Dried herbarium specimens of cyanobacteria (exsiccata) deposited over 100 years
      ago were analysed and characterized using combined morphological and molecular
      approaches. Six representative coccoid and filamentous cyanobacteria from two
      historic collections and a 15-year-old air-dried environmental sample were
      studied. Morphological features observed by light and electron microscopy were
      correlated with the results of 16S rRNA gene sequencing. Historic identifications
      achieved by means of classical morphology could thus be confirmed by extracted,
      amplified and sequenced 16S rRNA gene fragments. The results of this study open
      the possibility of providing genotypic characterizations to botanical type
      specimens, thus reconciling the botanical and bacteriological approaches to the
      taxonomic treatment of these micro-organisms.

PMID- 17012545
TI  - Gordonia defluvii sp. nov., an actinomycete isolated from activated sludge foam.
AB  - Three strains of non-motile, Gram-positive, filamentous actinomycetes, isolates
      J4(T), J5 and J59, initially recognized microscopically in activated sludge foam
      by their distinctive branching patterns, were isolated by micromanipulation. The
      taxonomic positions of the isolates were determined using a polyphasic approach.
      Almost-complete 16S rRNA gene sequences of the isolates were aligned with
      corresponding sequences of representatives of the suborder Corynebacterineae and
      phylogenetic trees were inferred using three tree-making algorithms. The
      organisms formed a distinct phyletic line in the Gordonia 16S rRNA gene tree. The
      three isolates showed 16S rRNA gene sequence similarities within the range 96.9
      97.2 % with their nearest phylogenetic neighbours, namely Gordonia bronchialis
      DSM 43247(T) and Gordonia terrae DSM 43249(T). Strain J4(T) was shown to have a
      chemotaxonomic profile typical of the genus Gordonia and was readily
      distinguished from representatives of the genus on the basis of Curie-point
      pyrolysis mass spectrometric data. The isolates shared nearly identical
      phenotypic profiles that distinguished them from representatives of the most
      closely related Gordonia species. It is evident from the genotypic and phenotypic
      data that the three isolates belong to a novel Gordonia species. The name
      proposed for this taxon is Gordonia defluvii sp. nov.; the type strain is J4(T)
      (=DSM 44981(T)=NCIMB 14149(T)).

PMID- 17012546
TI  - Marinomonas ostreistagni sp. nov., isolated from a pearl-oyster culture pond in
      Sanya, Hainan Province, China.
AB  - A Gram-negative, aerobic, halophilic, neutrophilic, rod-shaped, non-pigmented,
      polar-flagellated bacterium, UST010306-043(T), was isolated from a pearl-oyster
      culture pond in Sanya, Hainan Province, China in January 2001. This marine
      bacterium had an optimum temperature for growth of between 33 and 37 degrees C.
      On the basis of 16S rRNA gene sequence analysis, the strain was closely related
      to Marinomonas aquimarina and Marinomonas communis, with 97.5-97.7 and 97.1 %
      sequence similarity, respectively. Levels of DNA-DNA relatedness to the type
      strains of these species were well below 70 %. Analyses of phylogenetic,
      phenotypic and chemotaxomonic characteristics showed that strain UST010306-043(T)
      was distinct from currently established Marinomonas species. A novel species with
      the name Marinomonas ostreistagni sp. nov. is proposed to accommodate this
      bacterium, with strain UST010306-043(T) (=JCM 13672(T)=NRRL B-41433(T)) as the
      type strain.

PMID- 17012547
TI  - Geodermatophilaceae fam. nov., a formal description.
AB  - The family name 'Geodermatophilaceae' was first published by Normand et al.
      (1996) to contain the genera Geodermatophilus and Blastococcus, but a formal
      description and the designation of the type genus were not included, thus making
      the name invalid. Since then, the genus Modestobacter has been described as a
      member of the family 'Geodermatophilaceae' by Mevs et al. (2000). We hereby
      formally describe the family 'Geodermatophilaceae' which includes the recently
      described genus Modestobacter. The type genus of the family is Geodermatophilus.

PMID- 17012548
TI  - Isolates of 'Candidatus Nostocoida limicola' Blackall et al. 2000 should be
      described as three novel species of the genus Tetrasphaera, as Tetrasphaera
      jenkinsii sp. nov., Tetrasphaera vanveenii sp. nov. and Tetrasphaera veronensis
      sp. nov.
AB  - Despite differences in their morphologies, comparative analyses of 16S rRNA gene
      sequences revealed high levels of similarity (>94 %) between strains of the
      filamentous bacterium 'Candidatus Nostocoida limicola' and the cocci Tetrasphaera
      australiensis and Tetrasphaera japonica and the rod Tetrasphaera elongata, all
      isolated from activated sludge. These sequence data and their chemotaxonomic
      characters, including cell wall, menaquinone and lipid compositions and
      fingerprints of their 16S-23S rRNA intergenic regions, support the proposition
      that these isolates should be combined into a single genus containing six
      species, in the family Intrasporangiaceae in the Actinobacteria. This suggestion
      receives additional support from DNA-DNA hybridization data and when partial
      sequences of the rpoC1 gene are compared between these strains. Even though few
      phenotypic characterization data were obtained for these slowly growing isolates,
      it is proposed, on the basis of the extensive chemotaxonomic and molecular
      evidence presented here, that 'Candidatus N. limicola' strains Ben 17, Ben 18,
      Ben 67, Ben 68 and Ben 74 all be placed into the species Tetrasphaera jenkinsii
      sp. nov. (type strain Ben 74(T)=DSM 17519(T)=NCIMB 14128(T)), 'Candidatus N.
      limicola' strain Ben 70 into Tetrasphaera vanveenii sp. nov. (type strain Ben
      70(T)=DSM 17518(T)=NCIMB 14127(T)) and 'Candidatus N. limicola' strains Ver 1 and
      Ver 2 into Tetrasphaera veronensis sp. nov. (type strain Ver 1(T)=DSM
      17520(T)=NCIMB 14129(T)).

PMID- 17012549
TI  - Roseomonas aquatica sp. nov., isolated from drinking water.
AB  - Strain TR53(T), a Gram-negative, non-motile, non-spore-forming and strictly
      aerobic coccobacillus, isolated from the drinking water distribution system of
      Seville, Spain, was subjected to polyphasic taxonomic analysis using a
      combination of phenotypic, genotypic and phylogenetic features. Phylogenetic
      analysis of 16S rRNA gene sequences showed that strain TR53(T) had highest
      similarity to members of the genus Roseomonas, with sequence similarity values
      between 95.7 % (to Roseomonas genomospecies 5 strain ATCC 49960) and 94.0 % (to
      Roseomonas gilardii subsp. rosea ATCC 49956(T)). On the basis of its phenotypic
      characteristics, 16S rRNA gene sequence data and DNA G+C content (68.6 mol%),
      strain TR53(T) represents a novel species of the genus Roseomonas, for which the
      name Roseomonas aquatica sp. nov. is proposed. The type strain of Roseomonas
      aquatica is TR53(T) (=CECT 7131(T)=JCM 13556(T)).

PMID- 17012550
TI  - Amycolatopsis australiensis sp. nov., an actinomycete isolated from arid soils.
AB  - The taxonomic position of a group of mesophilic actinomycetes isolated from arid
      Australian soils was determined using a polyphasic approach. The organisms shared
      chemical and morphological markers typical of members of the genus Amycolatopsis.
      They had identical 16S rRNA gene sequences and formed a distinct phyletic line in
      the Amycolatopsis mediterranei clade, being most closely related to A.
      mediterranei. In addition, they shared a range of phenotypic properties that
      distinguished them from representatives of all of the species classified in this
      clade. The combined genotypic and phenotypic data indicate that the strains merit
      species status within the genus Amycolatopsis. The name proposed for the novel
      species is Amycolatopsis australiensis sp. nov.; the type strain is GY048(T)
      (=DSM 44671(T)=NCIMB 14142(T)).

PMID- 17012551
TI  - Dermacoccus barathri sp. nov. and Dermacoccus profundi sp. nov., novel
      actinomycetes isolated from deep-sea mud of the Mariana Trench.
AB  - The taxonomic positions of two actinobacterial strains isolated from Mariana
      Trench sediment were established using a combination of genotypic and phenotypic
      data. The strains, isolates MT2.1(T) and MT2.2(T), formed a distinct phyletic
      line in the Micrococcineae 16S rRNA gene tree together with Dermacoccus abyssi
      NCIMB 14084(T). The isolates had chemical and phenotypic properties typical of
      members of the genus Dermacoccus and could be distinguished sharply from one
      another and from the type strains of Dermacoccus abyssi and Dermacoccus
      nishinomiyaensis using DNA-DNA relatedness data. A range of phenotypic properties
      served to distinguish the two novel strains from one another and from the type
      strains of established Dermacoccus species. The G+C contents of the DNAs of
      strains MT2.1(T) and MT2.2(T) were 66.8 and 69.1 mol%, respectively. It is
      evident that the two isolates merit recognition as novel species within the genus
      Dermacoccus. The names proposed for these taxa are Dermacoccus barathri sp. nov.
      (type strain MT2.1(T)=DSM 17574(T)=NCIMB 14081(T)) and Dermacoccus profundi sp.
      nov. (type strain MT2.2(T)=DSM 17575(T)=NCIMB 14126(T)) [corrected]

PMID- 17012552
TI  - Actinoalloteichus hymeniacidonis sp. nov., an actinomycete isolated from the
      marine sponge Hymeniacidon perleve.
AB  - A polyphasic study was undertaken to establish the taxonomic status of a Gram
      positive, aerobic actinomycete, strain HPA177(T), isolated from a marine sponge,
      Hymeniacidon perleve. The organism formed branching, non-fragmenting vegetative
      hyphae and produced black pigment. Chemotaxonomic characteristics were consistent
      with its assignment to the genus Actinoalloteichus. Analysis of the 16S rRNA gene
      sequence showed that strain HPA177(T) formed a robust clade with type strains of
      the genus Actinoalloteichus, but was distinct from them. A number of phenotypic
      characteristics also readily distinguished strain HPA177(T) from species of the
      genus Actinoalloteichus with validly published names. On the basis of the above
      data, it is proposed that strain HPA177(T) represents a novel species,
      Actinoalloteichus hymeniacidonis sp. nov. The type strain of Actinoalloteichus
      hymeniacidonis is HPA177(T) (=CGMCC 4.2500(T)=JCM 13436(T)).

PMID- 17012553
TI  - Microcella alkaliphila sp. nov., a novel member of the family Microbacteriaceae
      isolated from a non-saline alkaline groundwater, and emended description of the
      genus Microcella.
AB  - A high-G+C-content Gram-positive bacterium, designated as strain AC4r(T), was
      isolated from a highly alkaline, non-saline groundwater environment (pH 11.4).
      This organism formed small rod-shaped cells, was aerobic, heterotrophic, catalase
      positive and oxidase-negative and had an optimum growth temperature of 35 degrees
      C and an optimum pH of 9.5. The strain possessed a B2beta-type cell-wall
      peptidoglycan, with d-Orn as the diagnostic diamino acid. The major respiratory
      quinones were unsaturated menaquinones with 13 and 14 isoprene units. The
      predominant fatty acids were anteiso-15 : 0, iso-16 : 0, iso-14 : 0 and iso-15 :
      0. The G+C content of the DNA was 67.1 mol%. In a 16S rRNA gene sequence
      analysis, strain AC4r(T) showed the highest level of similarity (99.2 %) to the
      type strain of Microcella putealis; however, the DNA-DNA reassociation value
      between these two organisms was low (38.3 %). On the basis of phylogenetic
      analysis, the DNA-DNA reassociation value and distinct phenotypic
      characteristics, strain AC4r(T) represents a novel species within the genus
      Microcella, for which the name Microcella alkaliphila sp. nov. is proposed. The
      type strain is AC4r(T) (=LMG 22690(T)=CIP 108473(T)).

PMID- 17012554
TI  - Lishizhenia caseinilytica gen. nov., sp. nov., a marine bacterium of the phylum
      Bacteroidetes.
AB  - A light-orange, aerobic bacterium, strain UST040201-001(T), that degrades casein,
      gelatin and Tween 20, was isolated in February 2004 from a sand-filtered seawater
      sample from Port Shelter, Hong Kong SAR, China. The strain possessed menaquinone
      6 and its 16S rRNA gene sequence shared only 90.1 % similarity with that of
      Brumimicrobium glaciale IC156(T). Phylogenetic analysis showed that UST040201
      001(T) formed a distinct lineage within the family Cryomorphaceae. Its
      ecophysiological and biochemical characteristics suggest that this strain
      represents a novel genus and species within the phylum Bacteroidetes. The name
      Lishizhenia caseinilytica gen. nov., sp. nov. is proposed. The type strain of
      Lishizhenia caseinilytica is UST040201-001(T) (=NRRL B-41434(T)=JCM 13821(T)).

PMID- 17012555
TI  - Description of Wautersiella falsenii gen. nov., sp. nov., to accommodate clinical
      isolates phenotypically resembling members of the genera Chryseobacterium and
      Empedobacter.
AB  - A total of 26 isolates of non-fermenting, Gram-negative rods, obtained between
      1980 and 2004 by various clinical laboratories in Belgium, with phenotypic
      characteristics resembling those of members of the genera Chryseobacterium and
      Empedobacter (indole-positive) and a biochemical profile resembling that of CDC
      group II-h, but urease-positive, were collected at the Universite Catholique de
      Louvain Microbiology Laboratory, Belgium. The 16S rRNA gene sequences were
      determined for most of the isolates and showed 94-95 % similarity with the type
      strain of Empedobacter brevis as the closest relative, indicating that these
      isolates might belong to a separate genus. Furthermore, the 16S rRNA gene
      sequences of the isolates were similar, but two clusters (genomovars) could be
      distinguished. The sequence similarities were 99.5-100 % for the 14 isolates of
      genomovar 1 and 99.4-100 % for the 12 isolates of genomovar 2. The similarity
      between the two clusters was 98.3-99.5 %. The presence of two clearly different
      groups was corroborated by using tRNA intergenic length polymorphism analysis,
      which also enabled differentiation of the novel species from all other species
      studied thus far using this technique. DNA-DNA hybridization results excluded a
      close relatedness to Empedobacter brevis. The DNA G+C contents of the reference
      strains of genomovars 1 and 2 were 33.8+/-0.4 and 34.4+/-0.2 mol%, respectively.
      The name Wautersiella falsenii gen. nov., sp. nov., is proposed for this group,
      comprising two closely related genomovars. The type strain of the species and
      reference strain for genomovar 1 is NF 993(T) (=CCUG 51536(T)=CIP 108861(T)),
      which was isolated from a surgical wound. The reference strain for genomovar 2 is
      NF 770 (=CCUG 51537=CIP 108860), which was isolated from blood.

PMID- 17012556
TI  - Syntrophomonas cellicola sp. nov., a spore-forming syntrophic bacterium isolated
      from a distilled-spirit-fermenting cellar, and assignment of Syntrophospora
      bryantii to Syntrophomonas bryantii comb. nov.
AB  - A spore-forming, anaerobic, syntrophic fatty-acid-oxidizing bacterium, strain 19J
      3(T), was isolated from a distilled-spirit-fermenting cellar in Hebei Province,
      China. The cells were slightly curved rods with a spore at the end of the cell.
      The optimal temperature for growth was around 37 degrees C and growth occurred in
      the range 25-45 degrees C. The pH range for growth was 6.5-8.5 and the optimum pH
      was 7.0-7.5. Crotonate was the only substrate that allowed the strain to grow in
      pure culture. However, the strain could oxidize saturated fatty acids with four
      to nine carbon atoms syntrophically in co-culture with Methanobacterium
      formicicum DSM 1535(T). The strain was not able to utilize sulfate, sulfite,
      thiosulfate, DMSO, nitrate, fumarate or Fe(III) as electron acceptor. The DNA
      base composition was 48.8 mol% G+C. Phylogenetic analysis based on the 16S rRNA
      gene sequence revealed that strain 19J-3(T) was related to members of the family
      Syntrophomonadaceae and most closely to Syntrophospora bryantii DSM 3014(T) (94.3
      % similarity) and Syntrophomonas wolfei subsp. wolfei DSM 2245(T) (93.6 %
      similarity). Considering the phylogenetic relationship and phenotypic features,
      strain 19J-3(T) (=CGMCC 1.5041(T)=JCM 13582(T)) is designated as the type strain
      of a novel species of the genus Syntrophomonas, Syntrophomonas cellicola sp. nov.
      Based on the close phylogenetic relationship between the genera Syntrophospora
      and Syntrophomonas, the presence of sporulation-specific genes in the genome of
      Syntrophomonas wolfei subsp. wolfei DSM 2245(T) and the description of a spore
      forming member of Syntrophomonas, 'Syntrophomonas erecta subsp. sporosyntropha',
      we propose the assignment of Syntrophospora bryantii to the genus Syntrophomonas
      as Syntrophomonas bryantii comb. nov.

PMID- 17012557
TI  - Plantibacter auratus sp. nov., in the family Microbacteriaceae.
AB  - Strain NCIMB 9991(T) is a Gram-positive, short rod-shaped, yellow-pigmented
      bacterium, with a high DNA G+C content, and was originally deposited in 1967 as
      Arthrobacter sp. The bacterium is aerobic, non-motile, catalase-positive and
      oxidase-negative. Comparative 16S rRNA gene sequencing studies demonstrated that
      this strain was highly related genealogically to Plantibacter flavus DSM
      14012(T). Strain IAM 14817(T) (=NCIMB 9991(T)) has the following characteristics:
      the predominant menaquinones are MK-9 and MK-10, the DNA G+C content is 68 mol%,
      the diamino acid in the cell wall is 2,4-l-diaminobutyric acid and the muramic
      acid in the peptidoglycan is of an acetyl type. The major fatty acid is 12-methyl
      tetradecanoic acid (anteiso-C(15 : 0)), followed by 14-methyl hexadecanoic acid
      (anteiso-C(17 : 0)), 14-methyl pentadecanoic acid (iso-C(16 : 0)) and
      hexadecanoic acid (C(16 : 0)). On the basis of morphological, physiological and
      chemotaxonomic characteristics, together with DNA-DNA hybridization and 16S rRNA
      gene sequence comparison, strain IAM 14817(T) represents a novel species within
      the genus Plantibacter, for which the name Plantibacter auratus sp. nov. is
      proposed, with the type strain IAM 14817(T) (=NCIMB 9991(T)=NBRC 15702(T)).

PMID- 17012558
TI  - Paenibacillus sepulcri sp. nov., isolated from biodeteriorated mural paintings in
      the Servilia tomb.
AB  - In 2001, a Gram-variable, facultatively anaerobic, endospore-forming bacterium
      isolated from biodeteriorated mural paintings in the Servilia tomb of the Roman
      necropolis of Carmona was deposited as Paenibacillus strain LMG 19508.
      Subsequently, the strain was characterized in detail using phenotypic and
      molecular methods. The 16S rRNA gene sequence confirmed that the strain belongs
      to the genus Paenibacillus and indicated its relationship to Paenibacillus
      mendelii CCM 4839(T) (96.7 % sequence similarity). The predominant menaquinone
      was MK-7. The cell wall contained meso-diaminopimelic acid of the A1gamma type.
      The DNA G+C content (50 mol%) and the major fatty acid (anteiso-C(15 : 0)) of
      strain LMG 19508(T) were also consistent with its affiliation to the genus
      Paenibacillus. DNA-DNA hybridization distinguished strain LMG 19508(T) from other
      phylogenetically related Paenibacillus species. Therefore, the isolate represents
      a novel species, for which the name Paenibacillus sepulcri sp. nov. is proposed.
      The type strain is CCM 7311(T) (=LMG 19508(T)).

PMID- 17012559
TI  - Oenococcus kitaharae sp. nov., a non-acidophilic and non-malolactic-fermenting
      oenococcus isolated from a composting distilled shochu residue.
AB  - Six strains of lactic acid bacteria were isolated in Japan from a composting
      distilled shochu residue. The six isolates grew poorly on MRS agar and slowly in
      MRS broth. The 16S rRNA gene sequences did not show high levels of similarity to
      those of the recognized species of lactic acid bacteria, and formed a subcluster
      within the cluster comprising obligately heterofermentative lactic acid bacteria
      closely related to Oenococcus oeni. The levels of DNA-DNA relatedness revealed
      that the isolates belonged to the same taxon and were genetically separate from
      O. oeni. Furthermore, various phenotypic characteristics such as the optimum pH
      for growth, malolactic fermentation and resistance to 10 % ethanol revealed that
      the isolates are distinguishable from O. oeni. On the basis of their phylogenetic
      and phenotypic characteristics, the isolates represent a novel species, for which
      the name Oenococcus kitaharae sp. nov. is proposed. The type strain is NRIC
      0645(T) (=JCM 13282(T)=DSM 17330(T)).

PMID- 17012560
TI  - Reclassification of Thermoterrabacterium ferrireducens as Carboxydothermus
      ferrireducens comb. nov., and emended description of the genus Carboxydothermus.
AB  - Similarities in phylogeny and metabolic properties between the type species of
      two monospecific genera of thermophilic anaerobic bacteria, Carboxydothermus
      hydrogenoformans and Thermoterrabacterium ferrireducens, and analysis of their
      recently available 16S rRNA gene sequences warranted clarification of their
      taxonomic positions. We have determined that the value of DNA-DNA hybridization
      between the type strains is 53 %. Additional physiological studies revealed that
      C. hydrogenoformans Z-2901(T) is capable of Fe(III) reduction with H(2) as an
      electron donor and ferrihydrite as an electron acceptor. T. ferrireducens JW/AS
      Y7(T) is able to grow and utilize CO with ferrihydrite as an electron acceptor
      without hydrogen or acetate production. We therefore reclassify
      Thermoterrabacterium ferrireducens as Carboxydothermus ferrireducens comb. nov.
      (type strain JW/AS-Y7(T)=DSM 11255(T)=VKM B-2392(T)). The description of the
      genus Carboxydothermus is emended to include such important physiological
      properties as growth on organic compounds and capacity for Fe(III) reduction.

PMID- 17012561
TI  - Halobacterium jilantaiense sp. nov., a halophilic archaeon isolated from a saline
      lake in Inner Mongolia, China.
AB  - A novel halophilic archaeon, NG4(T), was isolated from Jilantai salt lake in
      Inner Mongolia, China. The taxonomy of strain NG4(T) was studied by polyphasic
      methods. Strain NG4(T) grew at pH 5.5-8.5 and at a temperature of 22-55 degrees
      C. It was chemo-organotrophic, aerobic and required concentrations of 2.7-5.2 M
      NaCl and 0.05-0.3 M Mg(2+) for growth. Cells were Gram-negative, slender rods.
      Colonies on agar plates containing 25 % (w/v) total salts were red, elevated and
      round. According to 16S rRNA gene sequence similarity, strain NG4(T) was
      phylogenetically related to Halobacterium salinarum DSM 3754(T) (98.2 %) and
      Halobacterium noricense A1(T) (97.3 %). The DNA G+C content was 64.2 mol%. DNA
      DNA relatedness values with Hbt. salinarum DSM 3754(T) and Hbt. noricense A1(T)
      were 47 and 35 %, respectively. The polar lipids of strain NG4(T) consisted of
      phosphatidylglycerol, methylated phosphatidylglycerol phosphate,
      phosphatidylglycerol sulfate, triglycosyl diether, sulfated triglycosyl diether
      and sulfated tetraglycosyl diether. It was concluded that strain NG4(T)
      represents a novel species of the genus Halobacterium, for which the name
      Halobacterium jilantaiense sp. nov. is proposed. The type strain is NG4(T)
      (=CGMCC 1.5337(T)=JCM 13558(T)).

PMID- 17012562
TI  - Byssovorax cruenta gen. nov., sp. nov., nom. rev., a cellulose-degrading
      myxobacterium: rediscovery of 'Myxococcus cruentus' Thaxter 1897.
AB  - A rare, cellulose-decomposing myxobacterium is described, and a new genus name,
      Byssovorax, is proposed for it. The organism is almost certainly identical to the
      species 'Myxococcus cruentus' Thaxter 1897, and that species epithet is therefore
      revived for the novel bacterium: the type strain of Byssovorax cruenta gen. nov.,
      sp. nov., nom. rev. is strain By c2(T) (=DSM 14553(T)=CIP 108850(T)). The G+C
      content of its DNA is 69.9 mol%. The 16S rRNA gene sequence shows that the
      species belongs to the family Polyangiaceae, suborder 'Sorangineae', of the
      Myxococcales. An emended description of the organism is given.

PMID- 17012563
TI  - Rickettsia asiatica sp. nov., isolated in Japan.
AB  - The characterization of a novel Rickettsia species, first isolated from Ixodes
      ovatus ticks in Japan in 1993, is described for which the name Rickettsia
      asiatica sp. nov. is proposed. Using multilocus sequence comparison, five
      rickettsial isolates from I. ovatus collected at various locations in Japan were
      found to be identical but belonged to a novel species. Serotyping also
      demonstrated this rickettsia to be distinct from previously described Rickettsia
      species. The type strain of Rickettsia asiatica sp. nov. is IO-1(T) (=CSUR
      R2(T)). Following discussions held at the meeting of the International Committee
      on Systematics of Prokaryotes (ICSP) and its Judicial Commission (JC) in San
      Francisco, 2005, and in anticipation of the published minutes of the JC and ICSP,
      a committee consisting of the chairman of the ICSP, the chairman of the Judicial
      Commission of the ICSP and the Editor of the IJSEM has granted an exception in
      this case to the Rule governing the deposit of type material in two different
      collections in two different countries.

PMID- 17012564
TI  - Phycicoccus jejuensis gen. nov., sp. nov., an actinomycete isolated from seaweed.
AB  - A marine actinomycete strain, designated KSW2-15(T), was isolated from a dried
      seaweed sample collected from a sandy beach on the coast of Jeju in the Republic
      of Korea. The organism produced non-motile, non-endospore-forming, Gram-positive,
      coccoid cells. The colonies were circular, translucent and yellow in colour with
      entire margins. meso-Diaminopimelic acid was present as the diamino acid of the
      peptidoglycan. The acyl type of the muramic acid was acetyl. Mycolic acids were
      not present. The predominant menaquinone was MK-8(H(4)). The polar lipids were
      phosphatidylethanolamine, phosphatidylinositol and diphosphatidylglycerol. The
      major cellular fatty acids were of the saturated, unsaturated and iso-branched
      methyl types. The DNA G+C content was 74 mol%. Phylogenetic analyses based on 16S
      rRNA gene sequences revealed that strain KSW2-15(T) formed a loose association
      with 'Candidatus Nostocoida limicola', within the radiation of the family
      Intrasporangiaceae of the suborder Micrococcineae. The organism showed the
      highest levels of sequence similarity with 'Candidatus Nostocoida limicola' (96.1
      %), Terrabacter tumescens (96.1 %) and Terrabacter terrae (96.0 %). The levels of
      16S rRNA gene sequence similarity between the isolate and members of other genera
      of the family Intrasporangiaceae were in the range 92.1-95.5 %. On the basis of
      the polyphasic evidence, the isolate should be classified within a novel genus
      and species, for which the name Phycicoccus jejuensis gen. nov., sp. nov. is
      proposed. The type strain of Phycicoccus jejuensis is strain KSW2-15(T) (=KCCM
      42315(T)=NRRL B-24460(T)).

PMID- 17012565
TI  - Thiomicrospira halophila sp. nov., a moderately halophilic, obligately
      chemolithoautotrophic, sulfur-oxidizing bacterium from hypersaline lakes.
AB  - Enrichments at 2 M NaCl and pH 7.5-8, with thiosulfate or sulfide as electron
      donor, inoculated with sediments from hypersaline chloride-sulfate lakes of the
      Kulunda Steppe (Altai, Russia) resulted in the domination of two different groups
      of moderately halophilic, chemolithoautotrophic, sulfur-oxidizing bacteria. Under
      fully aerobic conditions with thiosulfate, bacteria belonging to the genus
      Halothiobacillus dominated while, under microaerophilic conditions, a highly
      motile, short vibrio-shaped phenotype outcompeted the halothiobacilli. Three
      genetically and phenotypically highly similar vibrio-shaped isolates were
      obtained in pure culture and one of them, strain HL 5(T), was identified as a
      member of the Thiomicrospira crunogena cluster by 16S rRNA gene sequencing. The
      new isolates were able to grow with thiosulfate as electron donor within a broad
      salinity range from 0.5 to 3.5 M NaCl with an optimum at 1.5 M and within a pH
      range from 6.5 to 8.5 with an optimum at pH 7.5-7.8. Comparative analysis of
      ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) gene sequences
      demonstrated that strain HL 5(T) possessed two genes, cbbL-1 and cbbL-2, of the
      form I RuBisCO and a cbbM gene of the form II RuBisCO, similar to the other
      members of the Thiomicrospira crunogena cluster. On the basis of phenotypic and
      genetic comparison, the new halophilic isolates are proposed to be placed into a
      novel species, Thiomicrospira halophila sp. nov. (type strain HL 5(T)=DSM
      15072(T)=UNIQEM U 221(T)).

PMID- 17012566
TI  - Micromonospora coriariae sp. nov., isolated from root nodules of Coriaria
      myrtifolia.
AB  - An actinomycete strain, NAR01(T), was isolated from root nodules of a Coriaria
      plant. The 16S rRNA gene sequence of strain NAR01(T) showed most similarity to
      the type strains of Micromonospora endolithica (98.94 %) and Micromonospora
      chersina (98.4 %). The chemotaxonomic results obtained confirmed the taxonomic
      position of the isolate within the genus Micromonospora, and revealed differences
      at the species level. Physiological and biochemical tests showed that strain
      NAR01(T) could be clearly distinguished from its closest phylogenetic neighbours,
      while DNA-DNA hybridization results indicated that the isolate represents a novel
      species. On the basis of these results, strain NAR01(T) (=DSM 44875(T)=LMG
      23557(T)) is proposed as the type strain of the novel species Micromonospora
      coriariae sp. nov.

PMID- 17012567
TI  - Paracoccus homiensis sp. nov., isolated from a sea-sand sample.
AB  - Strain DD-R11(T), isolated from a sea-sand sample from Homi Cape, Pohang city,
      South Korea, was a Gram-negative, aerobic, motile, non-spore-forming, rod- to
      ovoid-shaped bacterium. Colonies grown on marine agar were circular, convex and
      colourless to creamy white. Growth occurred between 10 and 40 degrees C (optimum
      25-30 degrees C) and at pH 5.0-9.0 (optimum pH 6.0-8.0). The strain could grow in
      up to 15 % NaCl (optimum 3-5 % NaCl). According to 16S rRNA gene sequence
      analysis, the strain was a member of the genus Paracoccus in the
      Alphaproteobacteria. Sequence similarities to type strains of the genus
      Paracoccus were between 94.6 and 98.3 %, showing the highest sequence similarity
      to Paracoccus zeaxanthinifaciens ATCC 21588(T). The DNA-DNA relatedness value of
      strain DD-R11(T) and P. zeaxanthinifaciens ATCC 21588(T) was 27 %. Strain DD
      R11(T) was characterized by having ubiquinone 10 as the major respiratory quinone
      and C(18 : 1)omega7c as the predominant fatty acid. The DNA G+C content was 63.0
      mol%. On the basis of its phenotypic and genotypic characteristics, it is
      suggested that DD-R11(T) represents a novel species of the genus Paracoccus, for
      which the name Paracoccus homiensis sp. nov. is proposed, with DD-R11(T) (=KACC
      11518(T)=DSM 17862(T)) as the type strain.

PMID- 17012568
TI  - Blastococcus jejuensis sp. nov., an actinomycete from beach sediment, and emended
      description of the genus Blastococcus Ahrens and Moll 1970.
AB  - A novel actinomycete, strain KST3-10(T), was isolated from sand sediment of a
      beach in Jeju, Korea, and was subjected to polyphasic taxonomic characterization.
      The organism produced circular, smooth, translucent, apricot-coloured colonies
      comprising coccoid- or rod-shaped cells. Phylogenetic analyses based on 16S rRNA
      gene sequences showed that the organism belonged to the family
      Geodermatophilaceae and consistently formed a distinct sub-branch outside the
      radiation of the genus Blastococcus. The organism showed 16S rRNA gene sequence
      similarity values of 98.2 % with respect to Blastococcus aggregatus DSM 4725(T)
      and 98.1 % with respect to Blastococcus saxobsidens BC444(T). The type strains of
      the two Blastococcus species shared 98.2 % sequence similarity with respect to
      each other, whereas the levels of sequence similarity between the novel organism
      and the type strains of the less closely related neighbours, Modestobacter
      multiseptatus and Geodermatophilus obscurus, were in the range 96.2-96.9 %. The
      physiological, biochemical and chemotaxonomic data revealed that the novel
      organism can be readily differentiated from members of the genus Blastococcus and
      that it merits separate species status. On the basis of the phenotypic and
      genotypic evidence, strain KST3-10(T) represents a novel species of the genus
      Blastococcus, for which the name Blastococcus jejuensis sp. nov. is proposed. The
      type strain is KST3-10(T) (=NRRL B-24440(T)=KCCM 42251(T)).

PMID- 17012570
TI  - Pediococcus ethanolidurans sp. nov., isolated from the walls of a distilled
      spirit-fermenting cellar.
AB  - Two novel Pediococcus strains, Z-9(T) and Z-17, were isolated from a distilled
      spirit-fermenting cellar in Hebei Province, China. The cells were Gram-positive,
      non-spore-forming, non-motile cocci and occurred in pairs or tetrads. The strains
      were facultatively anaerobic and produced only lactic acid [d(-) and l(+) isomers
      in the ratio 50 : 50] from glucose fermentation. Catalase activity was not
      present. Both strains were able to grow in 6.5 % ethanol and at pH 3.5, but not
      in 4 % NaCl. The mean genomic G+C content of the two strains was 39.5+/-0.5 mol%
      (39 mol% for the type strain, Z-9(T)). The levels of 16S rRNA gene sequence
      similarity between the two novel strains and related species of the genus
      Pediococcus ranged from 98.3 to 98.7 %. The levels of DNA-DNA relatedness between
      strain Z-9(T) and the phylogenetically closely related pediococci Pediococcus
      damnosus LMG 11484(T), Pediococcus inopinatus LMG 11409(T), Pediococcus parvulus
      LMG 11486(T) and Pediococcus cellicola LMG 22956(T) were 14.6, 33, 28.7 and 16.8
      %, respectively. On the basis of phenotypic, genotypic and phylogenetic analyses,
      a novel species, Pediococcus ethanolidurans sp. nov., is proposed, with strain Z
      9(T) (=AS 1.3889(T)=LMG 23354(T)) as the type strain.

PMID- 17012569
TI  - Polyphasic analysis indicates that Lactobacillus salivarius subsp. salivarius and
      Lactobacillus salivarius subsp. salicinius do not merit separate subspecies
      status.
AB  - Lactobacillus salivarius Rogosa et al. 1953 was described as a homofermentative
      lactobacillus with two varieties: salivarius, typified inter alia by the ability
      to ferment rhamnose, and salicinius, characterized by the ability to ferment the
      glucoside salicin. These varieties have become accepted as subspecies divisions.
      We have examined the relatedness of 32 L. salivarius strains by a polyphasic
      approach. Carbohydrate fermentation profile analysis did not support clear
      distinction of the two subspecies. L. salivarius UCC118 was shown to be
      facultatively heterofermentative, confirming in silico genome analysis. 16S rRNA
      gene sequences and 16S-23S rRNA intergenic spacer region sequences provided no
      discrimination between any of the strains or subspecies. Broad subdivisions were
      distinguishable by pulsed-field gel genomic digest patterns, but they did not
      allow subspecific or phenotypic distinctions. A phylogeny based upon groEL gene
      sequences was discordant with rhamnose or salicin fermentation data for many
      taxa, and no reliable phenotypic correlations could be established. In the
      absence of meaningful taxonomic criteria, we therefore propose that Lactobacillus
      salivarius comprises a single species with no infraspecific taxa. Based on the
      present study and literature data, an emended description of the species
      Lactobacillus salivarius is provided.

PMID- 17012571
TI  - Starkeya koreensis sp. nov., isolated from rice straw.
AB  - A facultatively chemolithoautotrophic, Gram-negative, aerobic, highly curved rod
      shaped, non-motile, non-spore-forming bacterium, strain Jip08(T), was isolated
      from rice straw in Daejeon, South Korea. Strain Jip08(T) produced colourless
      colonies (1.0-1.5 mm) on R2A medium after 3 days. On the basis of 16S rRNA gene
      sequence similarity, strain Jip08(T) was shown to belong to the alpha-2 subclass
      of the Proteobacteria, and was most closely related to Starkeya novella IAM
      12100(T) (98.6 %), Angulomicrobium tetraedale DSM 5895(T) (98.1 %),
      Angulomicrobium amanitiforme NCIMB 1785(T) (98.0 %), Ancylobacter aquaticus ATCC
      25396(T) (96.6 %) and Methylorhabdus multivorans DM13(T) (95.8 %), all of which
      belong to the family Hyphomicrobiaceae. The genomic DNA G+C content of strain
      Jip08(T) was 69 mol%. Chemotaxonomic data [major ubiquinone, Q-10; major fatty
      acids, C(18 : 1) isomer (summed feature of C(18 : 1)omega7c/omega9t/omega12t),
      C(19 : 0) cyclo omega8c and C(16 : 0)], 16S rRNA gene sequence analyses and some
      morphological and physiological features supported the affiliation of strain
      Jip08(T) to the genus Starkeya. However, DNA-DNA hybridization data and some
      phenotypic properties showed that strain Jip08(T) could be distinguished from the
      single known Starkeya species and represented a novel species, for which the name
      Starkeya koreensis sp. nov. is proposed. The type strain is Jip08(T) (=KCTC
      12212(T)=NBRC 100963(T)=IAM 15215(T)).

PMID- 17012572
TI  - Yonghaparkia alkaliphila gen. nov., sp. nov., a novel member of the family
      Microbacteriaceae isolated from an alkaline soil.
AB  - Two Gram-positive, non-motile, non-spore-forming and rod-shaped actinomycete
      strains, KSL-113(T) and KSL-133, were isolated from an alkaline soil in Korea,
      and their taxonomic positions were investigated by using a polyphasic approach.
      The strains grew optimally at 30 degrees C and pH 9.0. Phenotypic, phylogenetic
      and genetic similarities indicated that strains KSL-113(T) and KSL-133 represent
      the same species. Phylogenetic analyses based on 16S rRNA gene sequences showed
      that strains KSL-113(T) and KSL-133 fell within the family Microbacteriaceae of
      the suborder Micrococcineae, the highest 16S rRNA gene sequence similarity values
      (98.2 %) being obtained with respect to Microcella putealis CV-2(T). The 16S rRNA
      gene sequence similarities between strains KSL-113(T) and KSL-133 and the other
      members of the family Microbacteriaceae used in the phylogenetic analysis were
      less than 96.0 %. Strains KSL-113(T) and KSL-133 could be clearly distinguished
      from members of the family Microbacteriaceae on the basis of differences in
      chemotaxonomic properties, including the predominant menaquinone type, the cell
      wall peptidoglycan type and the fatty acid profile. Accordingly, on the basis of
      the combined phenotypic, chemotaxonomic and phylogenetic data, strains KSL-113(T)
      and KSL-133 constitute a novel genus and species of the family Microbacteriaceae,
      for which the name Yonghaparkia alkaliphila gen. nov., sp. nov. is proposed. The
      type strain of Yonghaparkia alkaliphila is KSL-113(T) (=KCTC 19126(T)=CIP
      108920(T)).

PMID- 17012573
TI  - Burkholderia ferrariae sp. nov., isolated from an iron ore in Brazil.
AB  - A Gram-negative, non-spore-forming bacterial strain with the ability to
      solubilize highly insoluble phosphatic minerals was isolated from a high
      phosphorous iron ore from Minas Gerais State, Brazil. This strain, designated
      FeGl01(T), was subjected to a polyphasic taxonomic investigation. Comparative 16S
      rRNA gene sequence analysis indicated that it formed a distinct phylogenetic
      lineage within the genus Burkholderia together with several other species of the
      genus, e.g. Burkholderia sacchari, Burkholderia tropica and Burkholderia unamae.
      Partial nucleotide sequencing and analysis of the recA gene roughly corroborated
      the phylogenetic position of strain FeGl01(T) within the genus Burkholderia. The
      chemotaxonomic properties of strain FeGl01(T), such as ubiquinone Q-8 as the
      predominant quinone system and C(16 : 0), C(17 : 0) cyclo, C(18 : 1)omega7c and
      C(19 : 0)omega8c cyclo as the major fatty acids, were also consistent with its
      classification within the genus Burkholderia. DNA-DNA hybridization experiments
      between strain FeGl01(T) and the type strains of B. unamae, B. sacchari and B.
      tropica yielded reassociation values of 40 % or lower, which, together with
      qualitative and quantitative differences in fatty acid composition and with
      differences in several phenotypic traits, support the separation of the new
      isolate from the phylogenetically most closely related species. Therefore, it is
      suggested that strain FeGl01(T) represents a novel species of the genus
      Burkholderia, for which the name Burkholderia ferrariae sp. nov. is proposed. The
      type strain is FeGl01(T) (=LMG 23612(T)=CECT 7171(T)=DSM 18251(T)).

PMID- 17012574
TI  - Kribbia dieselivorans gen. nov., sp. nov., a novel member of the family
      Intrasporangiaceae.
AB  - Two Gram-positive, catalase-positive, irregular short rod- or coccoid-shaped
      bacterial strains, N113(T) and R33, were isolated from an enrichment culture with
      diesel oil-degradation activity and their taxonomic positions were investigated
      using a polyphasic approach. Phenotypic, phylogenetic and genetic similarities
      indicated that strains N113(T) and R33 were representatives of the same species.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strains
      N113(T) and R33 form a lineage independent from those of members of the family
      Intrasporangiaceae. The novel isolates had cell-wall peptidoglycan based on meso
      diaminopimelic acid, MK-8(H(4)) as the predominant menaquinone and 10-methyl-C(18
      : 0), iso-C(16 : 0), C(18 : 1)omega9c, C(16 : 0) and C(18 : 0) as the major
      cellular fatty acids. The DNA G+C contents were 69.6-69.9 mol%. These
      chemotaxonomic properties, together with phylogenetic distinctiveness,
      distinguish the two novel strains from recognized members of the family
      Intrasporangiaceae. On the basis of phenotypic, phylogenetic and genetic data,
      strains N113(T) (=KCTC 19143(T)=JCM 13585(T)) and R33 are classified as
      representatives of a novel genus and species, Kribbia dieselivorans gen. nov.,
      sp. nov., within the family Intrasporangiaceae.

PMID- 17012575
TI  - Mesonia mobilis sp. nov., isolated from seawater, and emended description of the
      genus Mesonia.
AB  - The taxonomic position of a novel marine, heterotrophic, strictly aerobic,
      gliding and yellow-pigmented bacterium, designated strain KMM 6059(T), was
      determined. 16S rRNA gene sequence analysis revealed that this strain represents
      a member of the genus Mesonia. Phenotypic and chemotaxonomic data showed that the
      isolate represents a novel species of the genus Mesonia, for which the name
      Mesonia mobilis sp. nov. is proposed. The type strain is KMM 6059(T) (=KCTC
      12708(T)=LMG 23670(T)). An emended description of the genus Mesonia based on the
      new data is also given.

PMID- 17012576
TI  - Proposal of Roseburia faecis sp. nov., Roseburia hominis sp. nov. and Roseburia
      inulinivorans sp. nov., based on isolates from human faeces.
AB  - Seven recently cultured bacterial isolates, although similar in their 16S rRNA
      gene sequences to Roseburia intestinalis L1-82(T) (DSM 14610(T)), were not
      sufficiently related for inclusion within existing species, forming three
      separate clusters in a 16S rRNA gene phylogenetic tree. The isolates, which were
      obtained from human stools, were Gram-variable or Gram-negative, strictly
      anaerobic, slightly curved rods; cells from all strains measured approximately
      0.5x1.5-5.0 mum and were motile. Two strains belonging to one cluster (A2-181 and
      A2-183(T)) were the only strains that were able to grow on glycerol and that
      failed to grow on any of the complex substrates tested (inulin, xylan and
      amylopectin). Strains belonging to a second cluster (represented by M6/1 and
      M72/1(T)) differed from the other isolates in their ability to grow on sorbitol.
      Isolates belonging to a third cluster (L1-83 and A2-194(T)) were the only strains
      that failed to grow on xylose and that gave good growth on inulin (strains M6/1
      and M72/1(T) gave weak growth). All strains were net acetate utilizers. The DNA
      G+C contents of representative Roseburia strains A2-183(T), A2-194(T), M72/1(T)
      and R. intestinalis L1-82(T) were 47.4, 41.4, 42.0 and 42.6 mol%, respectively.
      Based on 16S rRNA gene sequence similarity, three novel Roseburia species are
      proposed, with the names Roseburia hominis sp. nov. (type strain A2-183(T)=DSM
      16839(T)=NCIMB 14029(T)), Roseburia inulinivorans sp. nov. (type strain A2
      194(T)=DSM 16841(T)=NCIMB 14030(T)) and Roseburia faecis sp. nov. (type strain
      M72/1(T)=DSM 16840(T)=NCIMB 14031(T)).

PMID- 17012577
TI  - Flavobacterium croceum sp. nov., isolated from activated sludge.
AB  - A Gram-negative, non-motile, rod-shaped bacterium, designated strain EMB47(T),
      was isolated from activated sludge performing enhanced biological phosphorus
      removal in a sequencing batch reactor. Growth was observed between 10 and 40
      degrees C (optimum, 25-35 degrees C) and between pH 5.0 and 8.5 (optimum, pH 7.5
      8.0). The predominant fatty acids of strain EMB47(T) were iso-C(16 : 0) 3-OH, iso
      C(15 : 1) G, C(15 : 0), iso-C(15 : 0), iso-C(14 : 0) and iso-C(16 : 0) and it
      contained phosphatidylethanolamine, diphosphatidylglycerol and
      phosphatidylcholine as polar lipids. The G+C content of the genomic DNA was 40.8
      mol% and the major quinone was MK-6. Comparative 16S rRNA gene sequence analyses
      showed that strain EMB47(T) formed a distinct phyletic line within the genus
      Flavobacterium. The levels of 16S rRNA gene sequence similarity with respect to
      Flavobacterium species were below 94.7 %. On the basis of the phenotypic,
      chemotaxonomic and molecular data, strain EMB47(T) represents a novel species
      within the genus Flavobacterium, for which the name Flavobacterium croceum sp.
      nov. is proposed. The type strain is EMB47(T) (=KCTC 12611(T)=DSM 17960(T)).

PMID- 17012578
TI  - Massilia aurea sp. nov., isolated from drinking water.
AB  - A Gram-negative, motile, rod-shaped organism, strain AP13(T), able to produce
      yellow-pigmented colonies, was isolated from the drinking water distribution
      system of Seville (Spain) and was characterized by using a polyphasic taxonomic
      approach. In 16S rRNA gene sequence comparisons, strain AP13(T) exhibited 96.9
      95.6 % similarity with respect to the five recognized species of the genus
      Massilia. The DNA G+C content of strain AP13(T) was 66.0 mol%, a value that
      supports the affiliation of strain AP13(T) to the genus Massilia. DNA-DNA
      hybridization data and phenotypic properties confirmed that strain AP13(T)
      represents a novel species of the genus Massilia, for which the name Massilia
      aurea sp. nov. is proposed. The type strain is AP13(T) (=CECT 7142(T)=CCM
      7363(T)=DSM 18055(T)=JCM 13879(T)).

PMID- 17012579
TI  - Flaviramulus basaltis gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae isolated from seafloor basalt.
AB  - Four yellow-pigmented, Gram-negative, motile strains were isolated from the
      glassy rind of submarine basaltic lava from the Jan Mayen area of the
      Norwegian/Greenland Sea at a depth of 1300 m below sea level. The four strains
      had identical 16S rRNA gene sequences and were indistinguishable in all
      phenotypic and chemotypic tests performed, indicating that they belonged to the
      same species. The strains had an obligately aerobic chemo-organotrophic
      metabolism. The strains were capable of growth at temperatures between -2 and 34
      degrees C, at pH between 6.5 and 8.6, and at sea salt concentrations between 3
      and 60 g l(-1). The strains were able to utilize organic acids, amino acids and
      sugars but not alcohols; they were also capable of hydrolysing a wide range of
      macromolecules. The predominant fatty acids were 15 : 0 iso, 15 : 1 iso, 15 : 0
      iso 3-OH and 17 : 0 iso 3-OH. The mean DNA G+C content of the strains was 31.4
      mol%. 16S rRNA gene sequence analysis indicated that the strains were affiliated
      to the genera Gaetbulibacter and Algibacter. However, phenotypic characteristics,
      especially aerobic metabolism, suggested that the strains should be placed within
      a new genus. On the basis of the polyphasic characterization of the four strains,
      it is suggested that the strains be included in the family Flavobacteriaceae as
      representatives of a novel species in a new genus, for which the name
      Flaviramulus basaltis gen. nov., sp. nov. is proposed. The type strain is H35(T)
      (=CIP 109091(T)=DSM 18180(T)).

PMID- 17012580
TI  - Bowmanella denitrificans gen. nov., sp. nov., a denitrifying bacterium isolated
      from seawater from An-Ping Harbour, Taiwan.
AB  - A heterotrophic, non-fermentative, denitrifying isolate, designated strain
      BD1(T), was obtained from a seawater sample collected in the shallow coastal
      region of An-Ping Harbour, Tainan, Taiwan. The cells of strain BD1(T) were Gram
      negative. Cells grown in broth cultures were curved rods that were motile by
      means of a single polar flagellum. Growth occurred between 10 and 40 degrees C,
      with an optimum at 30-35 degrees C. Strain BD1(T) grew in NaCl levels of 0-10 %,
      with better growth occurring at 1-3 %. It grew aerobically and could achieve
      anaerobic growth by adopting a denitrifying metabolism with nitrate or nitrous
      oxide as the terminal electron acceptor. The major fatty acids were C(16 : 0),
      C(18 : 1)omega7c and summed feature 3 (C(16 : 1)omega7c and/or C(15 : 0) iso 2
      OH). The polar lipids consisted of phosphatidylethanolamine (56.6 %) and
      phosphatidylglycerol (43.4 %). The isoprenoid quinones were Q-8 (81.5 %), Q-9
      (11.1 %) and Q-10 (7.4 %). The DNA G+C content was 50.0 mol%. A phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain BD1(T) formed a
      distinct lineage in the Gammaproteobacteria and that it exhibited the highest
      level of sequence similarity with species of the genera Alteromonas (92.8-93.7
      %), Aestuariibacter (93.0 %), Glaciecola (90.4-92.7 %) and Salinimonas (91.8 %).
      Strain BD1(T) was distinguishable from species of these genera by the presence of
      Q-9 and Q-10. Phenotypically, strain BD1(T) was also distinguishable from species
      of these genera in that it did not require NaCl for growth and was capable of
      denitrification. On the basis of the polyphasic data from this study, the isolate
      represents a novel species within a novel genus, for which the name Bowmanella
      denitrificans gen. nov., sp. nov. is proposed. The type strain of Bowmanella
      denitrificans is BD1(T) (=BCRC 17491(T)=JCM 13378(T)).

PMID- 17012581
TI  - Pseudolabrys taiwanensis gen. nov., sp. nov., an alphaproteobacterium isolated
      from soil.
AB  - A Gram-negative, short rod-shaped micro-organism (CC-BB4(T)) was isolated on
      nutrient agar from soil from Sinshe in Taichung County, Taiwan. Analysis of the
      16S rRNA gene sequence demonstrated that this isolate was novel, as it showed <92
      % similarity to the sequences of species of the genera Labrys, Beijerinckia and
      Methylocystis. The micro-organism did not utilize methylamine or methanol as a
      substrate, but was able to use several organic acids. The fatty acid profile was
      different from those reported for the genera Labrys, Beijerinckia, Methylocystis,
      Angulomicrobium, Methylorhabdus and Methyloarcula. On the basis of the 16S rRNA
      gene sequence analysis, in combination with chemotaxonomic and physiological
      data, strain CC-BB4(T) represents a novel genus, for which the name Pseudolabrys
      gen. nov. is proposed. The type species is Pseudolabrys taiwanensis sp. nov., and
      the type strain of P. taiwanensis is CC-BB4(T) (=CCUG 51779(T)=CIP 108932(T)).

PMID- 17012582
TI  - Morganella psychrotolerans sp. nov., a histamine-producing bacterium isolated
      from various seafoods.
AB  - Mesophilic Morganella morganii (n=6) and psychrotolerant M. morganii-like
      isolates from various seafoods (n=13), as well as clinical M. morganii isolates
      (n=3), were characterized by using a polyphasic approach including multi-locus
      sequencing. Based on the phylogenetic analysis, the 22 strains were divided into
      two distinct groups comprising mesophilic and psychrotolerant isolates,
      respectively. This classification was supported by DNA-DNA hybridization studies,
      whereby a psychrotolerant isolate (strain U2/3(T)) showed 41.0 and 17.8 %
      relatedness to the type strains of the mesophilic species Morganella morganii
      subsp. morganii (strain LMG 7874(T)) and Morganella morganii subsp. sibonii
      (strain DSM 14850(T)), respectively. Analysis of the 16S rRNA gene sequences
      showed a similarity of 98.6 % between mesophilic and psychrotolerant isolates.
      However, fragments of seven protein-encoding housekeeping genes (atpD, dnaN,
      gyrB, hdc, infB, rpoB and tuf) all showed less than 90.9 % sequence similarity
      between the two groups. The psychrotolerant isolates grew at 0-2 degrees C and
      also differed from the mesophilic M. morganii isolates with respect to growth at
      37 degrees C and in 8.5 % (w/v) NaCl and fermentation of d-galactose. The
      psychrotolerant strains appear to represent a novel species, for which the name
      Morganella psychrotolerans sp. nov. is proposed. The type strain is U2/3(T) (=LMG
      23374(T)=DSM 17886(T)).

PMID- 17012583
TI  - Updated phylogeny of the genus Aeromonas.
AB  - Recent phylogenetic studies of the genus Aeromonas based on gyrB and rpoD gene
      sequences have improved the phylogeny based on 16S rRNA gene sequences first
      published in 1992, particularly in the ability to split closely related species.
      These studies did not include the recently described species Aeromonas simiae and
      Aeromonas molluscorum and only a single strain of Aeromonas culicicola was
      available for analysis at that time. In the present work, these Aeromonas species
      and newly isolated strains of A. culicicola were examined. Sequence analysis
      indicates that A. simiae and A. molluscorum belong to non-described phylogenetic
      lines of descent within this genus, which supports the original description of
      both species. The most closely related species are Aeromonas schubertii and
      Aeromonas encheleia, respectively, which is consistent with 16S rRNA gene
      sequencing results. However, while the five strains of A. molluscorum showed
      nucleotide differences in their gyrB and rpoD gene sequences, the only two known
      A. simiae strains exhibited identical gene sequences, suggesting that they are
      isolates of the same strain. On the basis of the rpoD gene sequence phylogeny, A.
      culicicola strains from the original description and new isolates from drinking
      water and ornamental fish clustered within the species Aeromonas veronii,
      suggesting inconsistencies with previous results. Other strains with previously
      controversial taxonomy and new isolates from other studies were included in this
      study in order to clarify their phylogenetic affiliation at the species level.

PMID- 17012584
TI  - Metschnikowia orientalis sp. nov., an Australasian yeast from nitidulid beetles.
AB  - A novel species, Metschnikowia orientalis sp. nov., is described for haploid,
      heterothallic yeasts isolated from nitidulid beetles sampled in flowers in
      Rarotonga in the Cook Islands, and the Cameron Highlands of Malaysia. As
      evidenced by analysis of D1/D2 large subunit rDNA sequences, the species is
      related to Candida hawaiiana, to which it is similar in growth responses.
      Cylindrical, conjugated asci and acicular ascospores of moderate size are formed.
      Rudimentary mating reactions were observed with Metschnikowia aberdeeniae and
      Metschnikowia continentalis, but not with C. hawaiiana. The type strain of M.
      orientalis is UWOPS 99-745.6(T) (h(+)) (=CBS 10331(T)=NRRL Y-27991(T)) and the
      designated allotype is UWOPS 05-269.1 (h(-)) (=CBS 10330=NRRL Y-27992).

PMID- 17012585
TI  - Redefining Paracoccus denitrificans and Paracoccus pantotrophus and the case for
      a reassessment of the strains held by international culture collections.
AB  - An outline of the current taxonomic diversity of the genus Paracoccus is
      presented. A definitive summary is given of the valid type strains of Paracoccus
      denitrificans and Paracoccus pantotrophus and of culture collection strains that
      can be assigned to these species. The case is established for a critical
      reassessment of the P. denitrificans strains held by international culture
      collections, to ensure that they are assigned to the correct species.

PMID- 17012586
TI  - Identification of novel benzoylformate decarboxylases by growth selection.
AB  - A growth selection system was established using Pseudomonas putida, which can
      grow on benzaldehyde as the sole carbon source. These bacteria presumably
      metabolize benzaldehyde via the beta-ketoadipate pathway and were unable to grow
      in benzoylformate-containing selective medium, but the growth deficiency could be
      restored by expression in trans of genes encoding benzoylformate decarboxylases.
      The selection system was used to identify three novel benzoylformate
      decarboxylases, two of them originating from a chromosomal library of P. putida
      ATCC 12633 and the third from an environmental-DNA library. The novel P. putida
      enzymes BfdB and BfdC exhibited 83% homology to the benzoylformate decarboxylase
      from P. aeruginosa and 63% to the enzyme MdlC from P. putida ATCC 12633, whereas
      the metagenomic BfdM exhibited 72% homology to a putative benzoylformate
      decarboxylase from Polaromonas naphthalenivorans. BfdC was overexpressed in
      Escherichia coli, and the enzymatic activity was determined to be 22 U/ml using
      benzoylformate as the substrate. Our results clearly demonstrate that P. putida
      KT2440 is an appropriate selection host strain suitable to identify novel
      benzoylformate decarboxylase-encoding genes. In principle, this system is also
      applicable to identify a broad range of different industrially important enzymes,
      such as benzaldehyde lyases, benzoylformate decarboxylases, and hydroxynitrile
      lyases, which all catalyze the formation of benzaldehyde.

PMID- 17012587
TI  - Resistance of Listeria monocytogenes biofilms to sanitizing agents in a simulated
      food processing environment.
AB  - The objective of this study was to evaluate the resistance of biofilms of
      Listeria monocytogenes to sanitizing agents under laboratory conditions
      simulating a food processing environment. Biofilms were initially formed on
      stainless steel and Teflon coupons using a five-strain mixture of L.
      monocytogenes. The coupons were then subjected to repeated 24-h daily cycles.
      Each cycle consisted of three sequential steps: (i) a brief (60 s) exposure of
      the coupons to a sanitizing agent (a mixture of peroxides) or saline as a control
      treatment, (ii) storage of the coupons in sterile plastic tubes without any
      nutrients or water for 15 h, (iii) and incubation of the coupons in diluted
      growth medium for 8 h. This regimen was repeated daily for up to 3 weeks and was
      designed to represent stresses encountered by bacteria in a food processing
      environment. The bacteria on the coupons were reduced in number during the first
      week of the simulated food processing (SFP) regimen, but then adapted to the
      stressful conditions and increased in number. Biofilms repeatedly exposed the
      peroxide sanitizer in the SFP regimen developed resistance to the peroxide
      sanitizer as well as other sanitizers (quaternary ammonium compounds and
      chlorine). Interestingly, cells that were removed from the biofilms on peroxide
      treated and control coupons were not significantly different in their resistance
      to sanitizing agents. These data suggest that the resistance of the treated
      biofilms to sanitizing agents may be due to attributes of extracellular polymeric
      substances and is not an intrinsic attribute of the cells in the biofilm.

PMID- 17012588
TI  - Involvement of pyruvate oxidase activity and acetate production in the survival
      of Lactobacillus plantarum during the stationary phase of aerobic growth.
AB  - In addition to the previously characterized pyruvate oxidase PoxB, the
      Lactobacillus plantarum genome encodes four predicted pyruvate oxidases (PoxC,
      PoxD, PoxE, and PoxF). Each pyruvate oxidase gene was individually inactivated,
      and only the knockout of poxF resulted in a decrease in pyruvate oxidase activity
      under the tested conditions. We show here that L. plantarum has two major
      pyruvate oxidases: PoxB and PoxF. Both are involved in lactate-to-acetate
      conversion in the early stationary phase of aerobic growth and are regulated by
      carbon catabolite repression. A strain devoid of pyruvate oxidase activity was
      constructed by knocking out the poxB and poxF genes. In this mutant, acetate
      production was strongly affected, with lactate remaining the major end product of
      either glucose or maltose fermentation. Notably, survival during the stationary
      phase appeared to be dramatically improved in the poxB poxF double mutant.

PMID- 17012589
TI  - Detection of UV-induced thymine dimers in individual Cryptosporidium parvum and
      Cryptosporidium hominis oocysts by immunofluorescence microscopy.
AB  - To investigate the effect of UV light on Cryptosporidium parvum and
      Cryptosporidium hominis oocysts in vitro, we exposed intact oocysts to 4-, 10-,
      20-, and 40-mJ x cm-2 doses of UV irradiation. Thymine dimers were detected by
      immunofluorescence microscopy using a monoclonal antibody against cyclobutyl
      thymine dimers (anti-TDmAb). Dimer-specific fluorescence within sporozoite nuclei
      was confirmed by colocalization with the nuclear fluorogen 4',6'-diamidino-2
      phenylindole (DAPI). Oocyst walls were visualized using either commercial
      fluorescein isothiocyanate-labeled anti-Cryptosporidium oocyst antibodies (FITC
      CmAb) or Texas Red-labeled anti-Cryptosporidium oocyst antibodies (TR-CmAb). The
      use of FITC-CmAb interfered with TD detection at doses below 40 mJ x cm-2. With
      the combination of anti-TDmAb, TR-CmAb, and DAPI, dimer-specific fluorescence was
      detected in sporozoite nuclei within oocysts exposed to 10 to 40 mJ x cm-2 of UV
      light. Similar results were obtained with C. hominis. C. parvum oocysts exposed
      to 10 to 40 mJ x cm-2 of UV light failed to infect neonatal mice, confirming that
      results of our anti-TD immunofluorescence assay paralleled the outcomes of our
      neonatal mouse infectivity assay. These results suggest that our
      immunofluorescence assay is suitable for detecting DNA damage in C. parvum and C.
      hominis oocysts induced following exposure to UV light.

PMID- 17012590
TI  - Engineered cyanophycin synthetase (CphA) from Nostoc ellipsosporum confers
      enhanced CphA activity and cyanophycin accumulation to Escherichia coli.
AB  - The cyanophycin (CGP) synthetase gene (cphANE1) of the transposon-induced argL
      mutant NE1 of the cyanobacterium Nostoc ellipsosporum, which exhibits a CGP-leaky
      phenotype during diazotrophical growth, was cloned and expressed in Escherichia
      coli strain TOP10. Its amino acid sequence exhibited high similarities to CphAs
      of other cyanobacteria. Recombinant cells of E. coli, which harbored a fragment
      comprising the complete cphANE1 gene plus 400 bp of its downstream region in
      colinear orientation to the lacZ promoter, accumulated CGP up to 17 and 8.5%
      (wt/wt) of cellular dry matter (CDM) if cultivated in complex medium in the
      presence or absence of isopropyl-beta-D-thiogalactopyranoside, respectively. Two
      truncated CphAs, lacking 31 (CphANE1del96) or 59 (CphANE1del180) amino acids of
      the C-terminal region, were derived from cphANE1 by deleting 96 or 180 bp from
      its 3' region through the introduction of stop codons. In comparison to the wild
      type gene, cphANE1del96 conferred about 2.1- to 2.2-fold-higher enzyme activity
      (up to 5.75 U/mg protein) on E. coli. Furthermore, these cells accumulated about
      twofold more CGP (up to 34.5% [wt/wt] of CDM) than cells expressing the wild-type
      gene. An engineered CphA possessing significantly enhanced activity and
      conferring the highest CGP content on E. coli is demonstrated. In contrast,
      CphANE1del180 was inactive and did not confer CGP accumulation on E. coli.
      Interestingly, a short conserved stretch of 4 to 5 hydrophobic amino acids is
      located in the protein region present in CphANE1del96 but absent in
      CphANE1del180. In addition, CphANE1 and CphANE1del96 are, besides CphA from
      Acinetobacter baylyi, the only CphAs exhibiting rigid substrate specificities
      that do not enable the incorporation of lysine instead of arginine into CGP.

PMID- 17012591
TI  - Aerobic growth of Escherichia coli with 2,4,6-trinitrotoluene (TNT) as the sole
      nitrogen source and evidence of TNT denitration by whole cells and cell-free
      extracts.
AB  - Escherichia coli grew aerobically with 2,4,6-trinitrotoluene (TNT) as sole
      nitrogen source and caused TNT's partial denitration. This reaction was enhanced
      in nongrowing cell suspensions with 0.516 mol nitrite released per mol TNT. Cell
      extracts denitrated TNT in the presence of NAD(P)H. Isomers of amino-dimethyl
      tetranitrobiphenyl were detected and confirmed with U-15N-labeled TNT.

PMID- 17012592
TI  - Degradation of methanethiol by methylotrophic methanogenic archaea in a lab-scale
      upflow anaerobic sludge blanket reactor.
AB  - In a lab-scale upflow anaerobic sludge blanket reactor inoculated with granular
      sludge from a full-scale wastewater treatment plant treating paper mill
      wastewater, methanethiol (MT) was degraded at 30 degrees C to H2S, CO2, and CH4.
      At a hydraulic retention time of 9 h, a maximum influent concentration of 6 mM MT
      was applied, corresponding to a volumetric loading rate of 16.5 mmol liter-1 day
      1. The archaeal community within the reactor was characterized by anaerobic
      culturing and denaturing gradient gel electrophoresis analysis, cloning, and
      sequencing of 16S rRNA genes and quantitative PCR. Initially, MT-fermenting
      methanogenic archaea related to members of the genus Methanolobus were enriched
      in the reactor. Later, they were outcompeted by Methanomethylovorans hollandica,
      which was detected in aggregates but not inside the granules that originated from
      the inoculum, the microbial composition of which remained fairly unchanged.
      Possibly other species within the Methanosarcinacaea also contributed to the
      fermentation of MT, but they were not enriched by serial dilution in liquid
      media. The archaeal community within the granules, which was dominated by
      Methanobacterium beijingense, did not change substantially during the reactor
      operation. Some of the species related to Methanomethylovorans hollandica were
      enriched by serial dilutions, but their growth rates were very low.
      Interestingly, the enrichments could be sustained only in the presence of MT and
      did not utilize any of the other typical substrates for methylotrophic
      methanogens, such as methanol, methyl amine, or dimethylsulfide.

PMID- 17012593
TI  - Survival of Campylobacter spp. in darkling beetles (Alphitobius diaperinus) and
      their larvae in Australia.
AB  - Campylobacter infection is the most frequently reported notifiable food-borne
      disease in humans in Australia. Our studies investigated the persistence of
      Campylobacter spp. in or on darkling beetles (Alphitobius diaperinus) and their
      larvae. Our results in analyses with chickens confirm that, unless very short
      turnaround times are used (<72 h), beetles colonized in one production cycle
      (i.e., one batch of chickens) are most unlikely to still be colonized during the
      next cycle of chickens.

PMID- 17012594
TI  - Roles for cell wall glycopeptidolipid in surface adherence and planktonic
      dispersal of Mycobacterium avium.
AB  - The opportunistic pathogen Mycobacterium avium is a significant inhabitant of
      biofilms in drinking water distribution systems. M. avium expresses on its cell
      surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the
      core GPL in biofilm formation by M. avium and by other Mycobacterium species. In
      order to test this hypothesis in a directed fashion, three model systems were
      used to examine biofilm formation by mutants of M. avium with transposon
      insertions into pstAB (also known as nrp and mps). pstAB encodes the nonribosomal
      peptide synthetase that catalyzes the synthesis of the core GPL. The mutants did
      not adhere to polyvinyl chloride plates; however, they adhered well to plastic
      and glass chamber slide surfaces, albeit with different morphologies from the
      parent strain. In a model that quantified surface adherence under recirculating
      water, wild-type and pstAB mutant cells accumulated on stainless steel surfaces
      in equal numbers. Unexpectedly, pstAB mutant cells were >10-fold less abundant in
      the recirculating-water phase than parent strain cells. These observations show
      that GPLs are directly or indirectly required for colonization of some, but by no
      means all, surfaces. Under some conditions, GPLs may play an entirely different
      role by facilitating the survival or dispersal of nonadherent M. avium cells in
      circulating water. Such a function could contribute to waterborne M. avium
      infection.

PMID- 17012595
TI  - Culture conditions determine the balance between two different exopolysaccharides
      produced by Lactobacillus pentosus LPS26.
AB  - Lactobacillus pentosus LPS26, isolated from a natural fermentation of green
      olives, produces a capsular polymer constituted of two exopolysaccharides (EPS):
      EPS A, a high-molecular-weight (high-Mw) polysaccharide (1.9x10(6) Da) composed
      of glucose and rhamnose (3:1), and EPS B, a low-Mw polysaccharide (3.3x10(4) Da)
      composed of glucose and mannose (3:1). Fermentation experiments in a chemically
      semidefined medium with different carbon sources (glucose, fructose, mannitol,
      and lactose) showed that all of them except fructose supported EPS A production
      rather than EPS B production. The influence of temperature and pH was further
      analyzed. As the temperature dropped, increased synthesis of both EPS was
      detected. The control of pH especially enhanced EPS B production. With regard to
      this, the maximum total EPS production (514 mg liter-1) was achieved at a
      suboptimal growth temperature (20 degrees C) and pH 6.0. Continuous cultures
      showed that EPS A, synthesized mainly at low dilution rates, is clearly dependent
      on the growth rate, whereas EPS B synthesis was hardly affected. EPS production
      was also detected in supplemented skimmed milk, but no increase on the viscosity
      of the fermented milk was recorded. This could be linked to the high proportion
      of the low-Mw polysaccharide produced in these conditions in contrast to that
      observed in culture media. Overall, the present study shows that culture
      conditions have a clear impact on the type and concentration of EPS produced by
      strain LPS26, and consequently, these conditions should be carefully selected for
      optimization and application studies. Finally, it should be noted that this is,
      to our knowledge, the first report on EPS production by L. pentosus.

PMID- 17012596
TI  - Transformation of the green alga Haematococcus pluvialis with a phytoene
      desaturase for accelerated astaxanthin biosynthesis.
AB  - Astaxanthin is a high-value carotenoid which is used as a pigmentation source in
      fish aquaculture. Additionally, a beneficial role of astaxanthin as a food
      supplement for humans has been suggested. The unicellular alga Haematococcus
      pluvialis is a suitable biological source for astaxanthin production. In the
      context of the strong biotechnological relevance of H. pluvialis, we developed a
      genetic transformation protocol for metabolic engineering of this green alga.
      First, the gene coding for the carotenoid biosynthesis enzyme phytoene desaturase
      was isolated from H. pluvialis and modified by site-directed mutagenesis,
      changing the leucine codon at position 504 to an arginine codon. In an in vitro
      assay, the modified phytoene desaturase was still active in conversion of
      phytoene to zeta-carotene and exhibited 43-fold-higher resistance to the
      bleaching herbicide norflurazon. Upon biolistic transformation using the modified
      phytoene desaturase gene as a reporter and selection with norflurazon,
      integration into the nuclear genome of H. pluvialis and phytoene desaturase gene
      and protein expression were demonstrated by Southern, Northern, and Western
      blotting, respectively, in 11 transformants. Some of the transformants had a
      higher carotenoid content in the green state, which correlated with increased
      nonphotochemical quenching. This measurement of chlorophyll fluorescence can be
      used as a screening procedure for stable transformants. Stress induction of
      astaxanthin biosynthesis by high light showed that there was accelerated
      accumulation of astaxanthin in one of the transformants compared to the
      accumulation in the wild type. Our results strongly indicate that the modified
      phytoene desaturase gene is a useful tool for genetic engineering of carotenoid
      biosynthesis in H. pluvialis.

PMID- 17012597
TI  - Destruction of spores on building decontamination residue in a commercial
      autoclave.
AB  - The U.S. Environmental Protection Agency conducted an experiment to evaluate the
      effectiveness of a commercial autoclave for treating simulated building
      decontamination residue (BDR). The BDR was intended to simulate porous materials
      removed from a building deliberately contaminated with biological agents such as
      Bacillus anthracis (anthrax) in a terrorist attack. The purpose of the tests was
      to assess whether the standard operating procedure for a commercial autoclave
      provided sufficiently robust conditions to adequately destroy bacterial spores
      bound to the BDR. In this study we investigated the effects of several variables
      related to autoclaving BDR, including time, temperature, pressure, item type,
      moisture content, packing density, packing orientation, autoclave bag integrity,
      and autoclave process sequence. The test team created simulated BDR from
      wallboard, ceiling tiles, carpet, and upholstered furniture, and embedded in the
      BDR were Geobacillus stearothermophilus biological indicator (BI) strips
      containing 10(6) spores and thermocouples to obtain time and temperature profile
      data associated with each BI strip. The results indicated that a single standard
      autoclave cycle did not effectively decontaminate the BDR. Autoclave cycles
      consisting of 120 min at 31.5 lb/in2 and 275 degrees F and 75 min at 45 lb/in2
      and 292 degrees F effectively decontaminated the BDR material. Two sequential
      standard autoclave cycles consisting of 40 min at 31.5 lb/in2 and 275 degrees F
      proved to be particularly effective, probably because the second cycle's
      evacuation step pulled the condensed water out of the pores of the materials,
      allowing better steam penetration. The results also indicated that the packing
      density and material type of the BDR in the autoclave could have a significant
      impact on the effectiveness of the decontamination process.

PMID- 17012598
TI  - Diversity of ammonia-oxidizing archaea and bacteria in the sediments of a
      hypernutrified subtropical estuary: Bahia del Tobari, Mexico.
AB  - Nitrification within estuarine sediments plays an important role in the nitrogen
      cycle, both at the global scale and in individual estuaries. Although bacteria
      were once thought to be solely responsible for catalyzing the first and rate
      limiting step of this process, several recent studies have suggested that
      mesophilic Crenarchaeota are capable of performing ammonia oxidation. Here we
      examine the diversity (richness and community composition) of ammonia-oxidizing
      archaea (AOA) and bacteria (AOB) within sediments of Bahia del Tobari, a
      hypernutrified estuary receiving substantial amounts of ammonium in agricultural
      runoff. Using PCR primers designed to specifically target the archaeal ammonia
      monooxygenase alpha-subunit (amoA) gene, we found AOA to be present at five
      sampling sites within this estuary and at two sampling time points (January and
      October 2004). In contrast, the bacterial amoA gene was PCR amplifiable from only
      40% of samples. Bacterial amoA libraries were dominated by a few widely
      distributed Nitrosomonas-like sequence types, whereas AOA diversity showed
      significant variation in both richness and community composition. AOA communities
      nevertheless exhibited consistent spatial structuring, with two distinct end
      member assemblages recovered from the interior and the mouths of the estuary and
      a mixed assemblage from an intermediate site. These findings represent the first
      detailed examination of archaeal amoA diversity in estuarine sediments and
      demonstrate that diverse communities of Crenarchaeota capable of ammonia
      oxidation are present within estuaries, where they may be actively involved in
      nitrification.

PMID- 17012599
TI  - Mixed pollutant degradation by Methylosinus trichosporium OB3b expressing either
      soluble or particulate methane monooxygenase: can the tortoise beat the hare?
AB  - Methanotrophs have been widely investigated for in situ bioremediation due to
      their ubiquity and their ability to degrade halogenated hydrocarbons through the
      activity of methane monooxygenase (MMO). It has been speculated that cells
      expressing the soluble form of MMO (sMMO) are more efficient in cleaning up sites
      polluted with halogenated hydrocarbons due to its broader substrate range and
      relatively fast degradation rates compared cells expressing the other form of
      MMO, the particulate MMO (pMMO). To examine this issue, the biodegradation of
      mixtures of chlorinated solvents, i.e., trichloroethylene (TCE), trans
      dichloroethylene (t-DCE), and vinyl chloride (VC), by Methylosinus trichosporium
      OB3b in the presence of methane using either form of MMO was investigated over
      longer time frames than those commonly used, i.e., days instead of hours. Growth
      of M. trichosporium OB3b along with pollutant degradation were monitored and
      analyzed using a simple comparative model developed from the Omega model created
      for analysis of the competitive binding of oxygen and carbon dioxide by ribulose
      bisphosphate carboxylase. From these findings, it appears that at concentrations
      of VC, t-DCE, and TCE greater than 10 microM each, methanotrophs expressing pMMO
      have a competitive advantage over cells expressing sMMO due to higher growth
      rates. Despite such an apparent growth advantage, pMMO-expressing cells degraded
      less of these substrates at these concentrations than sMMO-expressing cells
      during active growth. If the concentrations were increased to 100 muM, however,
      not only did pMMO-expressing cells grow faster, they degraded more of these
      pollutants and did so in a shorter amount of time. These findings suggest that
      the relative rates of growth substrate and pollutant degradation are important
      factors in determining which form of MMO should be considered for pollutant
      degradation.

PMID- 17012600
TI  - NDR1 interaction with RIN4 mediates the differential activation of multiple
      disease resistance pathways in Arabidopsis.
AB  - Recognition of pathogens by plants involves the coordinated efforts of molecular
      chaperones, disease resistance (R) proteins, and components of disease resistance
      signaling pathways. Characterization of events associated with pathogen
      perception in Arabidopsis thaliana has advanced understanding of molecular
      genetic mechanisms associated with disease resistance and protein interactions
      critical for the activation of resistance signaling. Regulation of R protein
      mediated signaling in response to the bacterial pathogen Pseudomonas syringae in
      Arabidopsis involves the physical association of at least two R proteins with the
      negative regulator RPM1 INTERACTING PROTEIN4 (RIN4). While the RIN4-RPS2 (for
      RESISTANCE TO P. SYRINGAE2) and RIN4-RPM1 (for RESISTANCE TO P. SYRINGAE PV
      MACULICOLA1) signaling pathways exhibit differential mechanisms of activation in
      terms of effector action, the requirement for NON-RACE-SPECIFIC DISEASE
      RESISTANCE1 (NDR1) is shared. Using a yeast two-hybrid screen, followed by a
      series of coimmunoprecipitation experiments, we demonstrate that the RIN4-NDR1
      interaction occurs on the cytoplasmically localized N-terminal portion of NDR1
      and that this interaction is required for the activation of resistance signaling
      following infection by P. syringae expressing the Cys protease Type III effector
      protein AvrRpt2. We demonstrate that like RPS2 and RPM1, NDR1 also associates
      with RIN4 in planta. We suggest that this interaction serves to further regulate
      activation of disease resistance signaling following recognition of P. syringae
      DC3000-AvrRpt2 by Arabidopsis.

PMID- 17012601
TI  - Increased level of polyploidy1, a conserved repressor of CYCLINA2 transcription,
      controls endoreduplication in Arabidopsis.
AB  - Endoreduplication is a type of cell cycle in which DNA replication continues
      without cell division. We have isolated several dominant mutants from Arabidopsis
      thaliana activation tagging lines by flow cytometry. One of the mutants,
      increased level of polyploidy1-1D (ilp1-1D), showed increased polyploidy in both
      light- and dark-grown hypocotyls. The corresponding gene of ilp1-1D encodes a
      protein homologous to the C-terminal region of mammalian GC binding factor. We
      demonstrate that this protein functions as a transcriptional repressor in vivo.
      The expression of all members of the CYCLINA2 (CYCA2) family was reduced in an
      ILP1 overexpressing line, and the mouse (Mus musculus) homolog of ILP1 repressed
      cyclin A2 expression in mouse NIH3T3 cells. T-DNA insertion mutants of ILP1
      showed reduced polyploidy and upregulated all CYCA2 expression. Furthermore, loss
      of CYCA2;1 expression induces an increase in polyploidy in Arabidopsis. We
      demonstrate that this protein regulates endoreduplication through control of
      CYCA2 expression in Arabidopsis.

PMID- 17012602
TI  - The proteolytic processing of seed storage proteins in Arabidopsis embryo cells
      starts in the multivesicular bodies.
AB  - We have investigated the transport of storage proteins, their processing
      proteases, and the Vacuolar Sorting Receptor-1/Epidermal Growth Factor Receptor
      Like Protein1 (VSR-1/ATELP1) receptor during the formation of protein storage
      vacuoles in Arabidopsis thaliana embryos by means of high-pressure
      freezing/freeze substitution, electron tomography, immunolabeling techniques, and
      subcellular fractionation. The storage proteins and their processing proteases
      are segregated from each other within the Golgi cisternae and packaged into
      separate vesicles. The storage protein-containing vesicles but not the processing
      enzyme-containing vesicles carry the VSR-1/ATELP1 receptor. Both types of
      secretory vesicles appear to fuse into a type of prevacuolar multivesicular body
      (MVB). We have also determined that the proteolytic processing of the 2S albumins
      starts in the MVBs. We hypothesize that the compartmentalized processing of
      storage proteins in the MVBs may allow for the sequential activation of
      processing proteases as the MVB lumen gradually acidifies.

PMID- 17012603
TI  - Tocopherols play a crucial role in low-temperature adaptation and Phloem loading
      in Arabidopsis.
AB  - To test whether tocopherols (vitamin E) are essential in the protection against
      oxidative stress in plants, a series of Arabidopsis thaliana vitamin E (vte)
      biosynthetic mutants that accumulate different types and levels of tocopherols
      and pathway intermediates were analyzed under abiotic stress. Surprisingly subtle
      differences were observed between the tocopherol-deficient vte2 mutant and the
      wild type during high-light, salinity, and drought stresses. However, vte2, and
      to a lesser extent vte1, exhibited dramatic phenotypes under low temperature
      (i.e., increased anthocyanin levels and reduced growth and seed production). That
      these changes were independent of light level and occurred in the absence of
      photoinhibition or lipid peroxidation suggests that the mechanisms involved are
      independent of tocopherol functions in photoprotection. Compared with the wild
      type, vte1 and vte2 had reduced rates of photoassimilate export as early as 6 h
      into low-temperature treatment, increased soluble sugar levels by 60 h, and
      increased starch and reduced photosynthetic electron transport rate by 14 d. The
      rapid reduction in photoassimilate export in vte2 coincides with callose
      deposition exclusively in phloem parenchyma transfer cell walls adjacent to the
      companion cell/sieve element complex. Together, these results indicate that
      tocopherols have a more limited role in photoprotection than previously assumed
      but play crucial roles in low-temperature adaptation and phloem loading.

PMID- 17012604
TI  - Arabidopsis FHY3 specifically gates phytochrome signaling to the circadian clock.
AB  - Circadian gating of light signaling limits the timing of maximum responsiveness
      to light to specific times of day. The fhy3 (for far-red elongated hypocotyl3)
      mutant of Arabidopsis thaliana is involved in independently gating signaling from
      a group of photoreceptors to an individual response. fhy3 shows an enhanced
      response to red light during seedling deetiolation. Analysis of two independent
      fhy3 alleles links enhanced inhibition of hypocotyl elongation in response to red
      light with an arrhythmic pattern of hypocotyl elongation. Both alleles also show
      disrupted rhythmicity of central-clock and clock-output gene expression in
      constant red light. fhy3 exhibits aberrant phase advances under red light pulses
      during the subjective day. Release-from-light experiments demonstrate clock
      disruption in fhy3 during the early part of the subjective day in constant red
      light, suggesting that FHY3 is important in gating red light signaling for clock
      resetting. The FHY3 gating function appears crucial in the early part of the day
      for the maintenance of rhythmicity under these conditions. However, unlike
      previously described Arabidopsis gating mutants that gate all light signaling,
      gating of direct red light-induced gene expression in fhy3 is unaffected. FHY3
      appears to be a novel gating factor, specifically in gating red light signaling
      to the clock during daytime.

PMID- 17012605
TI  - Distinct KATP channels mediate the antihypertrophic effects of adenosine receptor
      activation in neonatal rat ventricular myocytes.
AB  - Recent evidence suggests that both adenosine receptor (AR) and K ATP channel
      activation exert antihypertrophic effects in cardiac myocytes. We studied the
      relative contributions of mitochondrial K ATP (mitoK ATP) and sarcolemmal K ATP
      (sarcK ATP) to the antihypertrophic effects of ARs in primary cultures of
      neonatal rat ventricular myocytes exposed for 24 h with the alpha1 adrenoceptor
      agonist phenylephrine (PE). The A1R agonist N6-cyclopentyladenosine (CPA), the
      A(2A)R agonist CGS21680 [2-p-(2-carboxyethyl)phenethylamino-5'-N
      ethylcarboxamidoadenosine], and the A3R agonist N6-(3-iodobenzyl)adenosine-5'
      methyluronamide (IB-MECA) all prevented PE-induced hypertrophy. Glibenclamide, a
      nonselective K(ATP) channel blocker reversed the antihypertrophic effect of all
      three AR agonists as determined by cell size and atrial natriuretic peptide
      expression and early c-fos up-regulation. In contrast, the mitoK(ATP) blocker 5
      hydroxydecanoic acid selectively attenuated the effect of CGS21680 and IB-MECA,
      whereas HMR1098 [1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]
      3-methylthiourea, sodium salt], a specific blocker of sarcK(ATP), only abolished
      the antihypertrophic effect of CPA. Moreover, both CGS21680 and IB-MECA but not
      CPA decreased the mitochondrial membrane potential when PE was present, similarly
      to that seen with diazoxide, and both agents inhibited PE-stimulated elevation in
      mitochondrial Ca2+. All AR agonists diminished PE-induced phosphoserine/threonine
      kinase and protein kinase B up-regulation, which was unaffected by any K(ATP)
      blocker. Our data suggest that AR-mediated antihypertrophic effects are mediated
      by distinct K(ATP) channels, with sarcK(ATP) mediating the antihypertrophic
      effects of A1R activation, whereas mitoK(ATP) activation mediates the
      antihypertrophic effects of both A(2A)R and A3R agonists.

PMID- 17012606
TI  - Selective activation of group III metabotropic glutamate receptors by L-(+)-2
      amino-4-phosphonobutryic acid protects the nigrostriatal system against 6
      hydroxydopamine toxicity in vivo.
AB  - Evidence from several studies suggests that the progressive degeneration of
      dopaminergic (DA) neurones of the substantia nigra pars compacta (SNc) in
      Parkinson's disease (PD) may in part be due to excessive release of glutamate
      from subthalamic projections onto nigral DA neurones. Previous in vitro studies
      have demonstrated that selective activation of Group III metabotropic glutamate
      receptors (mGluR) negatively modulates excitatory transmission in the SNc and is
      neuroprotective against glutamate-mediated toxicity. Consistent with this, we
      have reported preliminary data indicating that the selective group III mGluR
      agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4) can also protect the
      nigrostriatal system against 6-hydroxydopamine (6-OHDA) toxicity in vivo. We have
      now extended these preliminary studies in this model and report here that both
      acute and subchronic intranigral injections of l-AP4 provide significant
      protection of the nigrostriatal system against 6-OHDA toxicity. This
      neuroprotection displays a bell-shaped profile with a clear concentration
      dependent relationship. In contrast, when administered to animals 7 days post-6
      OHDA lesioning, l-AP4 significantly protects the functionality but not the
      integrity of the nigrostriatal system. We further demonstrate that
      neuroprotection by l-AP4 in vivo is reversed by coadministration of the selective
      Group III mGluR antagonist (RS)-alpha-methylserine-O-phosphate, confirming a
      receptor-mediated mechanism of action. These data provide further compelling
      evidence that selective activation of Group III mGluR is neuroprotective in an in
      vivo experimental model of PD, a finding that may have important implications for
      the future treatment of this disease.

PMID- 17012607
TI  - Roles of norepinephrine, free Fatty acids, thyroid status, and skeletal muscle
      uncoupling protein 3 expression in sympathomimetic-induced thermogenesis.
AB  - Thyroid hormone (TH) plays a fundamental role in thermoregulation, yet the
      molecular mediators of its effects are not fully defined. Recently, skeletal
      muscle (SKM) uncoupling protein (UCP) 3 was shown to be an important mediator of
      the thermogenic effects of the widely abused sympathomimetic agents 3,4
      methylenedioxymethamphetamine (MDMA; Ecstasy) and methamphetamine. Expression of
      UCP3 is regulated by TH. Activation of UCP3 is indirectly regulated by
      norepinephrine (NE) and is dependent upon the availability of free fatty acids
      (FFAs). We hypothesized that UCP3 may be a molecular link between TH and
      hyperthermia, requiring increased levels of both NE and FFAs to accomplish the
      thermogenic effect. Here, we demonstrate that MDMA (40 mg/kg s.c.) significantly
      increases plasma FFA levels 30 min after treatment. Pharmacologically increasing
      NE levels through the inhibition of phenylethanolamine N-methyltransferase with
      +/-2,3-dichloro-alpha-methylbenzylamine potentiated the hyperthermic effects of a
      20 mg/kg dose of MDMA. Using Western blots and regression analysis, we further
      illustrated that chronic hyperthyroidism in rats potentiates the hyperthermic
      effects of MDMA and increases levels of SKM UCP3 protein in a linear fashion
      according to levels of circulating plasma TH. Conversely, chronic hypothyroidism
      results in a hypothermic response to MDMA that is directly proportionate to
      decreased UCP3 expression. Acute TH supplementation did not change the skeletal
      muscle UCP3 expression levels or temperature responses to MDMA. These findings
      suggest that, although MDMA-induced hyperthermia appears to result from increased
      NE and FFA levels, susceptibility is ultimately determined by TH regulation of
      UCP3-dependent thermogenesis.

PMID- 17012608
TI  - Passive surveillance (1987 to 2004) of United Kingdom bats for European bat
      lyssaviruses.
AB  - Passive surveillance for European bat lyssaviruses (eblvs) in the uk began in
      1987, and between 1987 and 2004, 4,883 bats of European origin (4,871 belonging
      to 17 UK resident species and 12 belonging to seven non-uk resident species) were
      tested. The proportions and numbers of each species submitted from different
      regions varied considerably, partly owing to inherent biases in the passive
      surveillance, and there were seasonal variations in the numbers, sex and age of
      the bats. Contact with cats was reported in approximately 30 per cent of the bats
      submitted. Daubenton's bat (Myotis daubentonii) was the only species found to be
      positive for lyssavirus infection, with four cases of eblv type 2 identified, in
      1996, 2002, 2003 and 2004. No active infection with eblv type 1 was recorded.

PMID- 17012609
TI  - Fin erosion on rainbow trout on commercial trout farms in the United Kingdom.
AB  - Fish weighing less than 30 g and more than 100 g were sampled from 38 rearing
      units on 10 commercial farms growing rainbow trout for the table market. A fin
      index was calculated for each of the eight rayed fins on 949 trout by dividing
      their length by the standard length of the fish. There was a large range in the
      indices of all eight fins. The fin indices of the small and large fish were
      compared, controlling for farm effect. With the exception of the dorsal fin, all
      the indices were larger for the small fish than for the large fish, but the
      magnitude of the difference was greater for some fins than others. In comparison
      with the fins of wild fish, the pectoral and dorsal fins appeared to be most
      eroded and the damage to these fins was evident even in the small fish. The
      erosion of the caudal, anal and ventral (or pelvic) fins was more prominent in
      the larger fish. Variations in the fin indices of the caudal, anal and ventral
      fins suggested that there was little variation between rearing units on the same
      farm, but that there was significant variation between individual fish in the
      same rearing units, and between fish on different farms.

PMID- 17012610
TI  - Methods used in veterinary practice to maintain the temperature of intravenous
      fluids.
AB  - To determine the methods used in veterinary practice to maintain the temperature
      of intravenous fluids, and the users' impression of their efficacy, data were
      collected from a survey of 150 veterinary practices. Of the 99 per cent of the
      practices that warmed intravenous fluids, the use of a heat retention bag cover
      was most popular and was considered most effective. In a laboratory experiment,
      four methods of maintaining the temperature of intravenous fluids were compared.
      The results showed that there was a significant loss of heat through the giving
      set. A heat retention cover was an effective device for maintaining the
      temperature of the prewarmed fluid in its bag. The use of ;hot hands' (a sealed
      surgical glove containing warmed water) was most effective in reducing heat loss
      from the delivered fluid, and was aided by prewarming the giving set.

PMID- 17012611
TI  - Efficacy of a live bovine respiratory syncytial virus vaccine in seropositive
      calves.

PMID- 17012612
TI  - Intracranial granuloma caused by asporogenic Aspergillus fumigatus in a harbour
      porpoise (Phocoena phocoena).

PMID- 17012613
TI  - Treatment of squamous cell carcinoma in a horse.

PMID- 17012614
TI  - Reporting of clinical scrapie in the UK.

PMID- 17012615
TI  - FMD control strategies.

PMID- 17012616
TI  - Control of CBPP--a role for antibiotics?

PMID- 17012618
TI  - Ovariohysterectomy of cats.

PMID- 17012619
TI  - Structural determinants for high-affinity zolpidem binding to GABA-A receptors.
AB  - The imidazopyridine zolpidem (Ambien) is one of the most commonly prescribed
      sleep aids in the United States (Rush, 1998). Similar to classic benzodiazepines
      (BZDs), zolpidem binds at the extracellular N-terminal alpha/gamma subunit
      interface of the GABA-A receptor (GABAR). However, zolpidem differs significantly
      from classic BZDs in chemical structure and neuropharmacological properties.
      Thus, classic BZDs and zolpidem are likely to have different requirements for
      high-affinity binding to GABARs. To date, three residues--gamma2Met57,
      gamma2Phe77, and gamma2Met130--have been identified as necessary for high
      affinity zolpidem binding (Proc Natl Acad Sci USA 94:8824-8829, 1997; Mol
      Pharmacol 52:874-881, 1997). In this study, we used radioligand binding
      techniques, gamma2/alpha1 chimeric subunits (chi), site-directed mutagenesis, and
      molecular modeling to identify additional gamma2 subunit residues important for
      high-affinity zolpidem binding. Whereas alpha1beta2chi receptors containing only
      the first 161 amino-terminal residues of the gamma2 subunit bind the classic BZD
      flunitrazepam with wild-type affinity, zolpidem affinity is decreased
      approximately 8-fold. By incrementally restoring gamma2 subunit sequence, we
      identified a seven-amino acid stretch in the gamma2 subunit loop F region (amino
      acids 186-192) that is required to confer high-affinity zolpidem binding to
      GABARs. When mapped to a homology model, these seven amino acids make up part of
      loop F located at the alpha/gamma interface. Based on in silico zolpidem docking,
      three residues within loop F, gamma2Glu189, gamma2Thr193, and gamma2Arg194,
      emerge as being important for stabilizing zolpidem in the BZD binding pocket and
      probably interact with other loop F residues to maintain the structural integrity
      of the BZD binding site.

PMID- 17012620
TI  - Identification of small-molecule inhibitors of RGS4 using a high-throughput flow
      cytometry protein interaction assay.
AB  - Regulators of G-protein signaling (RGS) proteins are important components of
      signal transduction pathways initiated through G-protein-coupled receptors
      (GPCRs). RGS proteins accelerate the intrinsic GTPase activity of G-protein alpha
      subunits (Galpha) and thus shorten the time course and reduce the magnitude of G
      protein alpha- and betagamma-subunit signaling. Inhibiting RGS action has been
      proposed as a means to enhance the activity and specificity of GPCR agonist
      drugs, but pharmacological targeting of protein-protein interactions has
      typically been difficult. The aim of this project was to identify inhibitors of
      RGS4. Using a Luminex 96-well plate bead analyzer and a novel flow-cytometric
      protein interaction assay to assess Galpha-RGS interactions in a high-throughput
      screen, we identified the first small-molecule inhibitor of an RGS protein. Of
      3028 compounds screened, 1, methyl N-[(4-chlorophenyl)sulfonyl]-4
      nitrobenzenesulfinimidoate (CCG-4986), inhibited RGS4/Galpha(o) binding with 3 to
      5 muM potency. It binds to RGS4, inhibits RGS4 stimulation of Galpha(o) GTPase
      activity in vitro, and prevents RGS4 regulation of mu-opioid-inhibited adenylyl
      cyclase activity in permeabilized cells. Furthermore, CCG-4986 is selective for
      RGS4 and does not inhibit RGS8. Thus, we demonstrate the feasibility of targeting
      RGS/Galpha protein-protein interactions with small molecules as a novel means to
      modulate GPCR-mediated signaling processes.

PMID- 17012621
TI  - Characterization of beta2-adrenergic receptor dephosphorylation: Comparison with
      the rate of resensitization.
AB  - Dephosphorylation of the cyclic AMP-dependent protein kinase (PKA) site
      phosphoserine 262 and the G protein-coupled receptor kinase (GRK) site
      phosphoserines 355 and 356 of the beta2-adrenergic receptor (beta2AR) were
      characterized in both intact human embryonic kidney 293 cells and subcellular
      fractions and were correlated with the rate of resensitization of isoproterenol
      stimulation of adenylyl cyclase after treatment with isoproterenol and blockade
      by antagonist. Dephosphorylation of the PKA site after stimulation with 300 pM
      isoproterenol occurred with a t(1/2) of 9 min (k = 0.08 +/- 0.016/min) in intact
      cells in the absence of internalization. Dephosphorylation of the GRK sites in
      intact cells after treatment with 1.0 microM isoproterenol for 5 min exhibited a
      lag phase of approximately 5 min, after which dephosphorylation proceeded slowly
      with a t(1/2) of 18 min (k = 0.039 +/- 0.006/min). Consistent with the slow rate
      of GRK site dephosphorylation, the phosphatase inhibitors calyculin A and okadaic
      acid failed to augment phosphorylation in intact cells during continuous agonist
      stimulation indicating that GRK site dephosphorylation was minimal. However, both
      inhibited dephosphorylation of the GRK sites after the addition of antagonist.
      Slow GRK site dephosphorylation after antagonist treatment was also demonstrated
      by the relative stability of internalized phosphorylated beta2AR in cells as
      observed both by immunofluorescence microscopy using a phospho-site-specific
      antibody and by studies of the subcellular localization of the GRK-phosphorylated
      beta2AR on sucrose gradients that revealed nearly equivalent levels of GRK site
      phosphorylation in the plasma membrane and vesicular fractions. In addition,
      dephosphorylation of the GRK sites by intrinsic phosphatase activity occurred
      only in the heavy vesicle fractions. In contrast to the slow rates of
      dephosphorylation, the rate of resensitization of isoproterenol stimulation of
      adenylyl cyclase was 5- and 10-fold faster (k = 0.43 +/- 0.009/min; t(1/2) = 1.6
      min), than PKA and GRK site dephosphorylation, respectively, clearly dissociating
      the rapid phase of resensitization (0-5 min) from dephosphorylation.

PMID- 17012622
TI  - Short polybasic peptide sequences are potent inhibitors of PC5/6 and PC7: Use of
      positional scanning-synthetic peptide combinatorial libraries as a tool for the
      optimization of inhibitory sequences.
AB  - Positional scanning-synthetic peptide combinatorial libraries (PS-SPCLs) are
      powerful molecular tools to identify enzyme substrate and potent inhibitory
      sequences and also to provide crucial information about active site determinants.
      PS-SPCLs have been surveyed for furin, proprotein convertase (PC)2, PC1/3, and
      PACE4 and proven efficient to identify potent peptidyl inhibitors in the low
      nanomolar range for furin and PC1/3. We report herein the screenings of
      nonamidated and acetylated hexapeptide PS-SPCLs for PC5/6A and PC7. The L
      configuration library surveys distinctively revealed that L-Arg, L-Lys, and
      sometimes L-His in all six positions would generate the most potent inhibitors
      for both enzymes. Based on this clear polybasic preference, L-poly-Arg peptides
      ranging from four to nine residues were assayed. Inhibitory potency of these
      polybasic peptides increased with chain length, making nona-l-Arg a potent
      nanomolar inhibitor of PC5/6A and PC7 (Ki of 150 and 120 nM). PC5/6 and PC7
      inhibition by nona-l-arginine was equivalent to that of furin (Ki of 114 nM) (J
      Biol Chem 275: 36741-36749, 2000). Nona-d-arginine was a more potent inhibitor of
      PC5/6 and PC7 than its levorotatory version (Ki of 19 and 81 nM), reminiscent of
      furin (Ki of 1.3 nM) (J Biol Chem 279:36788-36794, 2004). Our data indicate that
      certain poly-arginine peptides represent potent inhibitors targeting PCs of the
      constitutive secretory pathway (furin, PC5/6, and PC7). We conclude that basic
      residues within PC peptide inhibitors might be responsible for targeting PCs in
      general and for inhibitory potency, but that select amino acid changes will be
      necessary to acquire true specificity toward a single PC.

PMID- 17012623
TI  - Adverse effects of maternal smoking during pregnancy on innate immunity in
      infants.

PMID- 17012624
TI  - Physical activity in patients with cystic fibrosis: A new variable in the health
      status equation unravelled?

PMID- 17012625
TI  - On Ca2+ sensitivity and the airways: Not just any smooth muscle.

PMID- 17012626
TI  - Learning to pair therapies and the expanding matrix for pulmonary arterial
      hypertension: Is more better?

PMID- 17012627
TI  - Improving the TB case management: The International Standards for Tuberculosis
      Care.

PMID- 17012628
TI  - Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary
      arterial hypertension.
AB  - Addition of inhaled iloprost to bosentan may have beneficial effects in patients
      with idiopathic pulmonary arterial hypertension (IPAH). A multicentre, open,
      randomised, controlled trial was performed to assess the safety and efficacy of
      inhaled iloprost in patients with IPAH who had already been treated with
      bosentan. The trial was terminated early after a futility analysis predicted
      failure with respect to the predetermined sample size. At that time, 40 patients
      were randomised to receive either bosentan alone (control group) or bosentan plus
      inhaled iloprost (combination group) for a 12-week period. The primary end-point,
      change in 6-min walking distance, was not met (mean changes +1 m and -9 m in the
      control and combination group, respectively). These results may have been skewed
      by three outliers in the iloprost group who presented with severe clinical
      worsening. None of the secondary end-points including functional class, peak
      oxygen uptake, and time to clinical worsening differed significantly between
      groups. The current study failed to show a positive effect of adding inhaled
      iloprost to bosentan in idiopathic pulmonary arterial hypertension patients.
      Further studies involving larger sample sizes and long-term follow-up are needed
      to determine the efficacy of adding inhaled iloprost to bosentan in patients with
      idiopathic pulmonary arterial hypertension.

PMID- 17012629
TI  - Parental smoking increases exhaled nitric oxide in young children.
AB  - The present study investigated the association between reported parental smoking
      and exhaled nitric oxide fraction (F(eNO)) in young children. In total, 78
      children (24 females, mean age 51.3 weeks) were recruited. Fourteen lived with
      one smoking parent and eight with two smoking parents. F(eNO) was measured using
      the modified single-breath technique. Mean+/-sd F(eNO) levels were 33.0+/-18.9,
      38.3+/-15.0 and 48.3+/-14.7 ppb for children with no, one and two smoking
      parents, respectively. There was a significant linear trend across the groups
      and, after controlling for other relevant factors, a significant difference
      between the groups. In the present study, exposure to environmental tobacco smoke
      was associated with increased exhaled nitric oxide fraction in young children.
      Furthermore, there was evidence of a dose-response relationship between childhood
      exhaled nitric oxide fraction and the number of smoking parents.

PMID- 17012630
TI  - Formoterol as needed with or without budesonide in patients with intermittent
      asthma and raised NO levels in exhaled air: A SOMA study.
AB  - Patients with mild intermittent asthma sometimes show signs of inflammation, and
      guidelines suggesting bronchodilator therapy alone as needed may be questioned.
      The current study compared as-needed use of a rapid-acting beta2-agonist with as
      needed use of a beta2-agonist and corticosteroid combination as the only
      medication in asthma patients with intermittent symptoms. A total of 92
      nonsmoking asthma patients (of 187 screened) using only an inhaled beta2-agonist
      as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume
      in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional
      exhaled nitric oxide (FeNO) > or =20 parts per billion (ppb)) were randomised to
      treatment with formoterol (Oxis Turbuhaler) 4.5 microg as needed (n = 47) or
      budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg as needed (n = 45) in
      a double-blind, parallel-group 24-week study. The primary variable of efficacy
      was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the
      budesonide/formoterol and formoterol groups, respectively. Mean reductions in
      FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8
      ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in
      the budesonide/formoterol group occurred during the first 4 weeks of treatment
      and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in
      the budesonide/formoterol group and decreased by 0.9% pred normal value in the
      formoterol group (95% CI -4.7- -0.7). In the budesonide/formoterol group, use of
      > or =4 inhalations x day(-1) of study medication was seen on 21 treatment days
      compared with 74 in the formoterol group. In conclusion, as-needed use of an
      inhaled corticosteroid together with a rapid-acting bronchodilator may be more
      beneficial than a beta2-agonist alone in patients with intermittent asthma and
      signs of airway inflammation. The long-term benefits are unknown.

PMID- 17012631
TI  - Advances in the diagnosis and management of chronic pulmonary aspiration in
      children.
AB  - Chronic pulmonary aspiration (CPA) in children is an important cause of recurrent
      pneumonia, progressive lung injury, respiratory disability and death. It is
      sporadic, intermittent and variable, and often occurs in children with
      complicated underlying medical conditions and syndromes that produce symptoms
      indistinguishable from CPA. For most types of aspiration there is no gold
      standard diagnostic test. The diagnosis of CPA is currently made clinically with
      some supporting diagnostic evaluations, but often not until significant lung
      injury has been sustained. Despite multiple diagnostic techniques, the diagnosis
      or exclusion of CPA in children is challenging. This is of particular concern
      given the outcome of unrecognised progressive lung injury and the invasiveness of
      definitive therapies. Although new techniques have been introduced since the
      1990s and significant advances in the understanding of dysphagia and gastro
      oesophageal reflux have been made, characterisation of the aspirating child
      remains elusive.

PMID- 17012632
TI  - Diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is an idiopathic inflammatory disease, well
      recognised in Japan and principally affecting the respiratory bronchioles,
      causing a progressive suppurative and severe obstructive respiratory disorder. If
      left untreated, DPB progresses to bronchiectasis, respiratory failure and death.
      It was first described in the early 1960s. Subsequently, in 1969, the disease was
      named DPB to distinguish it from chronic bronchitis. "Diffuse" refers to the
      distribution of the lesions throughout both lungs, and "pan-" refers to the
      involvement of inflammation in all layers of the respiratory bronchioles. The
      distinctive imaging and histological features, the coexisting sinusitis, and the
      isolation of Haemophilus influenzae and Pseudomonas aeruginosa in the sputum
      enhance disease recognition. Histologically, DPB is characterised by chronic
      inflammation, localised mainly in the respiratory bronchioles and adjacent
      centrilobular regions, with characteristic interstitial accumulation of foamy
      histiocytes, neutrophils and lymphocyte infiltration. Neutrophils and T
      lymphocytes, particularly CD8+ cells, together with the cytokines interleukin-8
      and macrophage inflammatory protein-1, are believed to play key roles in the
      development of DPB. A significant improvement in the prognosis of this
      potentially fatal disease has been recently reported thanks to the use of long
      term therapy with macrolide antibiotics, the effect of which is attributed to an
      anti-inflammatory and immunoregulatory action.

PMID- 17012633
TI  - Massive cavitary pulmonary rheumatoid nodules in a patient with HIV.
AB  - The case of a 52-yr-old female with rheumatoid arthritis and HIV who developed
      massive, progressive, cavitary pulmonary nodules is described. Multiple
      diagnostic bronchoscopies and lung biopsies failed to demonstrate the presence of
      any microorganisms. Pathological analysis showed palisading histiocytes with
      necrobiosis consistent with rheumatoid nodules. The effect of co-existing HIV
      infection on the course and prognosis of rheumatoid arthritis is discussed, and
      it is concluded that the complex relationship between these two disease processes
      warrants further investigation.

PMID- 17012634
TI  - A 13-year-old female with shortness of breath and pleuritic chest pain.

PMID- 17012635
TI  - Smoking and COPD: What really are the risks?

PMID- 17012636
TI  - High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic
      pulmonary fibrosis.

PMID- 17012637
TI  - Sandblasting jeans kills young people.

PMID- 17012638
TI  - Muscle impairments and behavioral factors mediate functional limitations and
      disability following stroke.
AB  - BACKGROUND AND PURPOSE: Stroke remains the leading cause of disability in the
      United States. The purposes of this study were to examine whether quantitative
      measures of muscle strength and power in the involved lower extremity predict
      functional limitations and to evaluate the contributions of behavioral factors to
      mediating disability and quality of life in people who have survived a stroke.
      SUBJECTS AND METHODS: A cross-sectional study design was used, and measurements
      of muscle impairment, lower-body function, disability, quality of life, and
      behavioral factors were obtained for 31 community-dwelling volunteers who had
      experienced a single ischemic stroke in the past 6 to 24 months. RESULTS:
      Stepwise regression models including impairment and behavioral measures were
      strong predictors of function, disability, and quality of life. Involved
      extremity muscle strength and power and self-efficacy were independently
      associated with function, whereas depression and self-efficacy were strong
      predictors of disability and quality of life. DISCUSSION AND CONCLUSION: The
      findings warrant future studies to determine whether interventions that address
      muscle strength and power, depressive symptoms, and low self-efficacy effectively
      improve function, reduce disability, and enhance quality of life in people who
      have survived a stroke.

PMID- 17012639
TI  - Reliability, sensitivity to change, and responsiveness of the peabody
      developmental motor scales-second edition for children with cerebral palsy.
AB  - BACKGROUND AND PURPOSE: The psychometric properties of the Peabody Developmental
      Motor Scales-Second Edition (PDMS-2), a revised motor test to assess both gross
      motor and fine motor composites in children with cerebral palsy (CP), are largely
      unknown. The purpose of this study was to examine the test-retest reliability and
      the responsiveness of the PDMS-2 for children with CP. SUBJECTS: A sample of 32
      children who had CP (age=27-64 months) and who received intervention participated
      in this study. METHODS: The PDMS-2 was administered to each child 3 times (at the
      beginning of the study, at 1 week, and at 3 months later) by a physical
      therapist. The agreement between the first 2 measurements was used to examine the
      reliability. The change between the first and the third measurements was used to
      examine the responsiveness. RESULTS: The composite scores on the PDMS-2 had good
      test-retest reliability (intraclass correlation coefficient=.88-1.00). The
      sensitivity-to-change coefficients ranged from 1.6 to 2.1, and the responsiveness
      coefficients ranged from 1.7 to 2.3. DISCUSSION AND CONCLUSION: Our results
      provide strong evidence that the 3 composites of the PDMS-2 had high test-retest
      reliability and acceptable responsiveness. The PDMS-2 can be used as an
      evaluative motor measure for children with CP and aged 2 to 5 years.

PMID- 17012640
TI  - Wrist extensor torque production and discomfort associated with low-frequency and
      burst-modulated kilohertz-frequency currents.
AB  - BACKGROUND AND PURPOSE: A randomized controlled trial to compare 2 forms of
      monophasic pulsed currents with 2 forms of burst-modulated, kilohertz-frequency
      alternating current ("Russian current" and "Aussie current") was conducted to
      establish whether different amounts of wrist extensor torque were produced and
      whether discomfort varied with stimulus type. SUBJECTS: The 32 subjects were
      adults who were healthy and were drawn from a population of staff and students at
      La Trobe University. METHODS: Each subject received all 4 currents. Maximal
      electrically induced torque (MEIT) of the wrist extensors was measured for each
      stimulus type. Relative discomfort of stimulation also was assessed. RESULTS:
      Russian current elicited lower mean torque than those elicited by Aussie current
      and monophasic pulsed currents. The Russian and Aussie currents elicited
      significantly less discomfort than the 2 monophasic pulsed currents. DISCUSSION
      AND CONCLUSION: When force production and relative discomfort were jointly used
      as the criteria, Aussie current was found to be more effective than either of the
      monophasic pulsed currents or Russian current stimulation.

PMID- 17012641
TI  - Effect of a virtual reality-enhanced exercise protocol after coronary artery
      bypass grafting.
AB  - BACKGROUND AND PURPOSE: Virtual reality (VR) technology has gained importance in
      many areas of medicine. Knowledge concerning the application and the influence of
      VR-enhanced exercise programs is limited for patients receiving coronary artery
      bypass grafting. The purpose of this study was to evaluate the effect of a
      virtual "country walk" on the number of sessions necessary to reach cardiac
      rehabilitation goals in patients undergoing coronary artery bypass grafting.
      SUBJECTS: Twenty subjects who were seen for cardiac rehabilitation between
      January and June 2004 comprised the study sample. METHODS: The protocol for this
      study included an initial maximum graded exercise tolerance test, given to
      determine the subsequent training goals for the subject, followed by biweekly
      submaximal endurance training sessions. All subjects were assigned by lot to 1 of
      2 submaximal endurance training programs, one (group 2) with and the other (group
      1) without the added VR environment. In all other respects, the 2 programs were
      identical. Each training session lasted for 30 minutes and was carried out twice
      per week for about 3 months. The primary outcome measures were maximum load
      during the work sessions, target oxygen consumption, target heart rate (beats per
      minute), and number of training sessions required to reach rehabilitation goals.
      RESULTS: By the end of 20 training sessions, only 4 of the 10 control subjects
      had reached the heart rate target goal of 85% their maximum heart rate. In
      contrast, 9 of the 10 subjects in the VR program had attained this goal by 9 or
      fewer training sessions. When target metabolic cost (75% peak oxygen consumption)
      was used as the training goal, all 10 subjects in the VR program had reached this
      target after 2 training sessions (or, in some cases, 1 training session), but not
      until training session 15 did a cumulative number of 9 control subjects reach
      this goal. DISCUSSION AND CONCLUSION: These study outcomes clearly support the
      notion that incorporating a VR environment into cardiac rehabilitation programs
      will accelerate maximum recovery of patients' cardiovascular function.

PMID- 17012642
TI  - Combined use of repetitive task practice and an assistive robotic device in a
      patient with subacute stroke.
AB  - BACKGROUND AND PURPOSE: This case report describes a training program comprising
      repetitive task practice (RTP) and robotic therapy for a patient with subacute
      stroke and resultant impaired upper-extremity function. CASE DESCRIPTION: A 63
      year-old man with right-sided hemiplegia resulting from a hemorrhagic stroke
      received a combined intervention of RTP and robotic therapy for 4 hours per day
      for 3 weeks. Clinical and kinetic evaluations were performed before and after
      intervention. OUTCOMES: Following the combined intervention, clinical
      improvements in hand function were observed, maximum grip force decreased
      slightly, and interlimb coupling decreased. DISCUSSION: An intervention of RTP
      with robotic therapy may be an effective method to improve upper-extremity
      function following stroke. Furthermore, the case suggests that improvements in
      strength are not necessary for improved dexterous function, provided that a
      minimal level of strength is present.

PMID- 17012643
TI  - Application of combined botulinum toxin type A and modified constraint-induced
      movement therapy for an individual with chronic upper-extremity spasticity after
      stroke.
AB  - BACKGROUND AND PURPOSE: Constraint-induced movement therapy (CIMT) is a promising
      intervention for retraining upper-extremity function after a stroke. The purpose
      of this case report is to describe the use of a combination of botulinum toxin
      type A (BtxA) and a modified CIMT program for a patient with severe spasticity
      who was unable to use his right upper extremity. CASE DESCRIPTION: The 52-year
      old patient, who had a stroke 4 years ago, did not meet the minimum motor
      criteria for CIMT benefit. After receiving BtxA injections targeting the elbow,
      wrist, and finger flexors, he completed a 4-week program of modified CIMT
      followed by a 5-month home exercise program. OUTCOMES: The patient exhibited
      improvement in muscle tone (the velocity-dependent resistance to stretch that
      muscle exhibits) and in scores on several upper-extremity function tests
      (Modified Ashworth Scale, Motor Activity Log, Wolf Motor Function Test, Action
      Research Arm Test, and Fugl-Meyer Assessment of Motor Recovery). He also reported
      making much progress in the functional use of the involved upper extremity.
      DISCUSSION: In a patient with severe flexor spasticity and nonuse of the dominant
      upper extremity after a stroke, a combined treatment of BtxA and modified CIMT
      may have resulted in improved upper-extremity use.

PMID- 17012644
TI  - Exercise for women with or at risk for breast cancer-related lymphedema.

PMID- 17012645
TI  - Neuroplasticity after spinal cord injury and training: an emerging paradigm shift
      in rehabilitation and walking recovery.
AB  - Physical rehabilitation after spinal cord injury has been based on the premise
      that the nervous system is hard-wired and irreparable. Upon this assumption,
      clinicians have compensated for irremediable sensorimotor deficits using braces,
      assistive devices, and wheelchairs to achieve upright and seated mobility.
      Evidence from basic science, however, demonstrates that the central nervous
      system after injury is malleable and can learn, and this evidence has challenged
      our current assumptions. The evidence is especially compelling concerning
      locomotion. The purpose of this perspective article is to summarize the evidence
      supporting an impending paradigm shift from compensation for deficits to
      rehabilitation as an agent for walking recovery. A physiologically based approach
      for the rehabilitation of walking has developed, translating evidence for
      activity-dependent neuroplasticity after spinal cord injury and the
      neurobiological control of walking. Advanced by partnerships among
      neuroscientists, clinicians, and researchers, critical rehabilitation concepts
      are emerging for activity-based therapy to improve walking recovery, with
      promising clinical findings.

PMID- 17012646
TI  - Locomotor training in people with Parkinson disease.
AB  - The purpose of this article is to consider the role of the physical therapist in
      locomotor training for people with Parkinson disease. The ways in which disease
      progression, medication status, environmental conditions, individual factors, and
      the goals of locomotor tasks contribute to clinical decision making are explored.
      Using the International Classification of Functioning, Disability and Health,
      gait training will be considered in relation to impairments of body structure and
      function, activity limitations, and participation restrictions in people who are
      newly diagnosed through to those with end-stage disease. Based on the principles
      of neural adaptation and clinical research findings, practical suggestions are
      made on how to provide the most efficient and effective physical therapy services
      at different stages of Parkinson disease.

PMID- 17012647
TI  - Is there evidence that proprioception or balance training can prevent anterior
      cruciate ligament (ACL) injuries in athletes without previous ACL injury?

PMID- 17012648
TI  - On "resting position variables..." Borstad. Phys ther. 2006;86(4):549-557.

PMID- 17012649
TI  - Weight-supported treadmill versus over-ground training after spinal cord injury:
      from a physical therapist's point of view.

PMID- 17012651
TI  - Prion diseases in humans: an update.
AB  - The year 2006 marks 20 years from the first identified bovine spongiform
      encephalitis in cows and 10 years from the first description of variant
      Creutzfeldt-Jakob disease in humans. The threatened epidemic in humans now
      appears unlikely, but psychiatrists need to be aware of recent developments in
      prion diseases.

PMID- 17012652
TI  - Costs and consequences of enhanced primary care for depression: systematic review
      of randomised economic evaluations.
AB  - BACKGROUND: A number of enhancement strategies have been proposed to improve the
      quality and outcome of care for depression in primary care settings. Decision
      makers are likely to need to know whether these interventions are cost-effective
      in routine primary care settings. METHOD: We conducted a systematic review of all
      full economic evaluations (cost-effectiveness and cost-utility analyses)
      accompanying randomised controlled trials of enhanced primary care for
      depression. Costs were standardised to UK pounds/US dollars and incremental cost
      effectiveness ratios (ICERs) were visually summarised using a permutation matrix.
      RESULTS: We identified 11 full economic evaluations (4757 patients). A near
      uniform finding was that the interventions based upon collaborative care/case
      management resulted in improved outcomes but were also associated with greater
      costs. When considering primary care depression treatment costs alone, ICER
      estimates ranged from 7 ($13, no confidence interval given) to 13 UK pounds
      ($24,95% CI -105 to 148) per additional depression-free day. Educational
      interventions alone were associated with increased cost and no clinical benefit.
      CONCLUSIONS: Improved outcomes through depression management programmes using a
      collaborative care/case management approach can be expected, but are associated
      with increased cost and will require investment.

PMID- 17012653
TI  - Dose escalation for insufficient response to standard-dose selective serotonin
      reuptake inhibitors in major depressive disorder: systematic review.
AB  - BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are
      frequently used for major depressive disorder, only 50-60% of patients respond to
      a standard dose. For non-responders, dose escalation is often applied. AIM: To
      systematically review the evidence for dose escalation of SSRIs. METHOD: A
      systematic literature search in MEDLINE, EMBASE, CINAHL and PsycInfo was
      performed. Randomised controlled trials and meta-analyses investigating dose
      escalation of SSRIs were identified. Relevant articles were retrieved and
      critically appraised. Results were summarised in an evidence table. Pooling was
      not justified because of heterogeneity of the identified studies. RESULTS: Eight
      true dose-escalation studies and three meta-analyses were identified. The
      available data provided no unequivocal base for dose escalation. Dose escalation
      before 4 weeks of treatment at a standard dose appeared to be ineffective.
      CONCLUSIONS: Dose escalation of SSRIs is equivocally supported by evidence of
      randomised controlled trials; methodological difficulties in the studies may
      account for this lack of evidence.

PMID- 17012654
TI  - Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder:
      family-based association study.
AB  - BACKGROUND: We have previously reported the Val66Met and GT(n) repeat
      polymorphisms of the brain-derived neurotrophic factor (BDNF) gene to be
      associated with bipolar disorder. However, these findings have not been
      replicated consistently. AIMS: To dissect the association of the BDNF gene with
      bipolar disorder by examining additional markers at the DNA level and by testing
      the illness categories of bipolar disorder I and II and rapid cycling. METHOD: We
      performed a family-based association study and haplotype analyses with 312
      nuclear families using four single nucleotide polymorphisms (SNPs) and the
      Val66Met and GT(n) repeat polymorphisms. RESULTS: The SNPs hCV11592756 and
      rs2049045, the Val66Met and GT(n) were significantly associated with bipolar
      disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and
      0.008 respectively). The effect atthese markers was mainly driven by the rapid
      cycling patients. CONCLUSIONS: Within bipolar disorder, variation in the BDNF
      gene appears to predict risk for developing rapid cycling according to DSM-IV.
      Incorporating this clinical sub-phenotyping into other studies of the BDNF gene
      may help to resolve some of the inconsistencies reported thus far concerning BDNF
      and bipolar disorder.

PMID- 17012655
TI  - Eating habits and attitudes among 10-year-old children of mothers with eating
      disorders: longitudinal study.
AB  - BACKGROUND: Children of mothers with eating disorders are at increased risk of
      developmental disturbance, but there has been little research in middle
      childhood, when disturbed eating habits tend to emerge. AIMS: To examine whether
      maternal eating disorders identified in the postnatal year are associated with
      the development of disturbed eating habits and attitudes in children at 10 years
      of age. METHOD: Follow-up comparative study of 56 families (33 mothers with
      eating disorders and 23 controls). Psychopathology of children, mothers and
      fathers was assessed by interview, and mother-child interaction observed.
      RESULTS: The index group of children scored higher than controls on three of four
      domains of eating disorder psychopathology and on a global score. Children's
      eating disturbance was associated with length of exposure to mothers' eating
      disorder and mother-child mealtime conflict at 5 years. There was some evidence
      of increased emotional problems in index children. CONCLUSIONS: The children of
      mothers with eating disorders manifested disturbed eating habits and attitudes
      compared with controls, and may be at heightened risk of developing frank eating
      disorder psychopathology.

PMID- 17012656
TI  - Use of standardised outcome measures in adult mental health services: randomised
      controlled trial.
AB  - BACKGROUND: Routine use of standardised outcome measures is not universal. AIMS:
      To evaluate the effectiveness of standardised outcome assessment. METHOD: A
      randomised controlled trial, involving 160 representative adult mental health
      patients and paired staff (ISRCTN16971059). The intervention group (n=101) (a)
      completed monthly postal questionnaires assessing needs, quality of life, mental
      health problem severity and therapeutic alliance, and (b) received 3-monthly
      feedback. The control group (n=59) received treatment as usual. RESULTS: The
      intervention did not improve primary outcomes of patient-rated unmet need and of
      quality of life. Other subjective secondary outcome measures were also not
      improved. The intervention reduced psychiatric inpatient days (3.5 v.16.4 mean
      days, bootstrapped 95% CI1.6-25.7), and hence service use costs were 2586 UK
      pounds (95% CI 102-5391) less for intervention-group patients. Net benefit
      analysis indicated that the intervention was cost-effective. CONCLUSIONS: Routine
      use of outcome measures as implemented in this study did not improve subjective
      outcomes, but was associated with reduced psychiatric inpatient admissions.

PMID- 17012657
TI  - Psychopathology, personality traits and social development of young first-degree
      relatives of patients with schizophrenia.
AB  - BACKGROUND: Evaluation of individuals at high genetic risk of schizophrenia is a
      powerful method for identifying precursors of the illness. AIMS: To identify
      aspects of personality, psychopathology and social development that differentiate
      high-risk and control individuals. METHOD: Adolescent and young-adult first
      degree relatives (n=35) of people with schizophrenia or schizoaffective disorder
      and a control group (n=55) were compared on 36 measures at baseline of a
      longitudinal study. Measures differentiating high-risk and control participants
      were related to four genetic loading indices. RESULTS: High-risk participants
      older than 17 years showed more physical anhedonia, less positive involvement
      with peers and more problems with peers, siblings and the opposite gender. Older
      high-risk individuals also were less cooperative, less self-directed and less
      reward-dependent. Problems with peers and the opposite gender, as well as reward
      dependence, were related linearly to genetic loading. CONCLUSIONS: Alterations in
      personality traits and social development are present in high-risk individuals,
      and may be markers for genetic liability toward the illness.

PMID- 17012658
TI  - Distribution of symptom dimensions across Kraepelinian divisions.
AB  - BACKGROUND: Dimensional structures are established for many psychiatric
      diagnoses, but dimensions have not been compared between diagnostic groups. AIMS:
      To examine the structure of dimensions in psychosis, to analyse their
      correlations with disease characteristics and to assess the relative contribution
      of dimensions v. diagnosis in explaining these characteristics. METHOD: Factor
      analysis of the OPCRIT items of 191 Maudsley Family Study patients with
      schizophrenia, mood disorders with psychosis, schizoaffective disorder, and other
      psychotic illnesses, followed by regression of disease characteristics from
      factor scores and diagnosis. RESULTS: Five factors were identified (mania,
      reality distortion, depression, disorganisation, negative); all were more
      variable in schizophrenia than in affective psychosis. Mania was the best
      discriminator between schizophrenia and affective psychosis; the negative factor
      was strongly correlated with poor premorbid functioning, insidious onset and
      worse course. Dimensions explained more of the disease characteristics than did
      diagnosis, but the explanatory power of the latter was also high. CONCLUSIONS:
      Kraepelinian diagnostic categories suffice for understanding illness
      characteristics, but the use of dimensions adds substantial information.

PMID- 17012659
TI  - Treatment engagement and violence risk in mental disorders.
AB  - BACKGROUND: Research has uncovered many characteristics related to violence
      committed by people with mental illness. However, relatively few studies have
      focused on understanding the connection between violence and dynamic, malleable
      variables such as a patient's level of treatment engagement. AIMS: To explore the
      link between community violence and patients'beliefs about psychiatric treatment
      benefit. METHOD: A sample of 1011 adults receiving out-patient treatment for a
      psychiatric disorder in the public mental health systems of five US states were
      interviewed. RESULTS: Bivariate analyses revealed community violence was
      inversely related to treatment adherence, perceived treatment need and perceived
      treatment effectiveness. Multivariate analyses showed these three variables were
      associated with reduced odds of violent and other aggressive acts. CONCLUSIONS:
      The results suggest clinical consideration of patients' perceptions of treatment
      benefit can help enhance violence risk assessment in psychiatric practice
      settings.

PMID- 17012660
TI  - Episodic psychiatric disorders in teenagers with learning disabilities with and
      without autism.
AB  - BACKGROUND: Mental health problems in people with learning disabilities and
      autism are poorly understood. AIMS: To investigate the prevalence of episodic
      psychiatric disorders in a sample of teenagers with learning disabilities with
      and without autism. METHOD: Teenagers with learning disabilities living in one
      geographical area were identified. Those with autism were matched to those
      without. A semi-structured investigator-based interview linked to Research
      Diagnostic Criteria was used to assess prevalence and type of episodic disorders.
      RESULTS: Significantly more individuals with autism had a lifetime episodic
      disorder, most commonly major depression. Two individuals with autism had bipolar
      affective disorder. Other episodic disorders with mood components and behaviour
      change were also evident, as were unclassifiable disorders characterised by
      complex psychiatric symptoms, chronicity and general deterioration.
      Antipsychotics and stimulants were most frequently prescribed; the former
      associated with episodic disorder, the latter with autism. CONCLUSIONS: Teenagers
      with learning disabilities and autism have higher rates of episodic psychiatric
      disorders than those with learning disabilities alone.

PMID- 17012661
TI  - Contribution of depression and anxiety to impaired health-related quality of life
      following first myocardial infarction.
AB  - BACKGROUND: The extent to which depression impairs health-related quality of life
      (HRQoL) in the physically ill has not been clearly established. AIMS: To quantify
      the adverse influence of depression and anxiety, assessed at the time of first
      myocardial infarction and 6 months later, on the physical aspect of HRQoL 12
      months after the infarction. METHOD: In all, 260 in-patients, admitted following
      first myocardial infarction, completed the Hospital Anxiety and Depression Scale
      and the Medical Outcomes Study SF-36 assessment before discharge and at 6- and 12
      month follow-up. RESULTS: Depression and anxiety 6 months after myocardial
      infarction predicted subsequent impairment in the physical aspects of HRQoL
      (attributable adjusted R(2)=9%, P<0.0005). These negative effects of depression
      and anxiety on outcome were mediated by feelings of fatigue. Depression and
      anxiety present before myocardial infarction did not predict HRQoL 12 months
      after myocardial infarction. CONCLUSIONS: Detection and treatment of depression
      and anxiety following myocardial infarction improve the patient's health-related
      quality of life.

PMID- 17012662
TI  - Influence of social perception and social knowledge on cognitive and social
      functioning in early psychosis.
AB  - BACKGROUND: Social cognition has been implicated in the relationship between
      cognition and social functioning. AIMS: To test the hypothesis that social
      cognition mediates the relationship between cognitive and social functioning.
      METHOD: This was a 1-year longitudinal cohort study comparing three groups: 50
      people with first-episode psychosis, 53 people with multi-episode schizophrenia
      and 55 people without psychiatric disorder as controls. Participants were
      assessed on social perception, social knowledge, interpersonal problem-solving,
      cognition and social functioning. RESULTS: There were significant associations
      between social cognition, cognition and social functioning in all three groups.
      Deficits in social cognition were stable over time. In the first two groups,
      controlling for social cognition reduced the relationship between cognitive and
      social functioning. CONCLUSIONS: This study provides some evidence that social
      cognition mediates the relationship between cognitive and social functioning.

PMID- 17012663
TI  - Culture and assessment of manic symptoms.
AB  - Cultural background may influence the perception of psychiatric symptoms. We
      examined the effects of cultural biases on the identification of manic symptoms
      using the Young Mania Rating Scale. Two video interviews, each with an American
      person with mania, were shown to psychiatrists from three countries (US, UK and
      India). Total scores on the scale differed significantly between the US and UK
      (P<0.001) and between India and UK (P<0.001) rater groups. Overall, differences
      between India and US rater groups were less marked (P=0.28). These differences
      suggest that cultural biases influence the interpretation of manic symptoms.

PMID- 17012664
TI  - Brain volume changes in the first year of illness and 5-year outcome of
      schizophrenia.
AB  - Progressive brain volume changes have been reported in first-episode
      schizophrenia, but their relationship to the disease process or to other factors
      remains unclear. We examined such changes in the first year of illness, and
      related them to 5-year outcome. Progressive brain volume changes, in particular
      of grey matter, during the first year of illness were found to be significantly
      associated with clinical and functional outcome 5 years after the first episode.
      These findings suggest that early dynamic brain volume changes are related to the
      disease process and predict the longer-term outcome of schizophrenia.

PMID- 17012665
TI  - Refugee doctors and the development of psychiatry.

PMID- 17012667
TI  - Drug treatment for psychotic depression.

PMID- 17012668
TI  - Recovery-oriented mental healthcare.

PMID- 17012669
TI  - When is transference work useful in dynamic psychotherapy?

PMID- 17012670
TI  - Is compulsive buying a real disorder, and is it really compulsive?

PMID- 17012671
TI  - Adult attention deficit hyperactivity disorder: moving beyond DSM-IV.

PMID- 17012672
TI  - Genetics and the future of clinical psychiatry.

PMID- 17012673
TI  - Beyond clinical utility: broadening the DSM-V research appendix to include
      alternative diagnostic constructs.

PMID- 17012674
TI  - Dopamine receptor response to NMDA stimulation.

PMID- 17012675
TI  - The nature of genetic influences on behavior: lessons from "simpler" organisms.
AB  - Substantial advances have been made in recent years in the understanding of the
      genetic basis of behavior in "simpler" organisms, especially the mouse and the
      fruit fly Drosophila. The authors examine the degree of similarity between the
      genetic underpinnings of psychiatric illness and genetic influences on behavior
      in such simpler organisms. Six topics are reviewed: 1) the extent of natural
      genetic variation, 2) the multigenic nature of natural variation, 3) the impact
      of individual genes on multiple traits, 4) gene-environment interactions, 5)
      genetic effects on the environment, and 6) gene-by-sex interactions. The results
      suggest that the pattern of results emerging in psychiatric genetics is generally
      consistent with the findings of behavioral genetics in simpler organisms. Across
      the animal kingdom, individual differences in behavior are nearly always
      influenced by genetic factors which, in turn, result from a substantial number of
      individual genes, each with a small effect. Nearly all genes that affect behavior
      influence multiple phenotypes. The impact of individual genes can be
      substantially modified by other genes and/or by environmental experiences. Many
      animals alter their environment, and the nature of that alteration is influenced
      by genes. For some behaviors, the pathway from genes to behavior differs
      meaningfully in males and females. With respect to the broad patterns of genetic
      influences on behavior, Homo sapiens appears to be typical of other animal
      species.

PMID- 17012676
TI  - Medication-induced weight gain and dyslipidemia in patients with schizophrenia.

PMID- 17012677
TI  - War and peace: psychotherapy with a holocaust survivor.

PMID- 17012678
TI  - Emil Wilhelm Magnus Georg Kraepelin (1856-1926).

PMID- 17012682
TI  - Diagnosing adult attention deficit hyperactivity disorder: are late onset and
      subthreshold diagnoses valid?
AB  - OBJECTIVE: Diagnosing attention deficit hyperactivity disorder (ADHD) in adults
      is difficult when diagnosticians cannot establish an onset before the DSM-IV
      criterion of age 7 or if the number of symptoms recalled does not achieve DSM's
      diagnosis threshold. METHOD: The authors addressed the validity of DSM-IV's age
      at-onset and symptom threshold criteria by comparing four groups of adults: 127
      subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79
      subjects with late-onset ADHD who met all criteria except the age-at-onset
      criterion, 41 subjects with subthreshold ADHD who did not meet full symptom
      criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria.
      The authors hypothesized that subjects with late-onset and subthreshold ADHD
      would show patterns of psychiatric comorbidity, functional impairment, and
      familial transmission similar to those seen in subjects with full ADHD. RESULTS:
      Subjects with late-onset and full ADHD had similar patterns of psychiatric
      comorbidity, functional impairment, and familial transmission. Most children with
      late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and
      showed a different pattern of familial transmission than the other forms of ADHD.
      CONCLUSIONS: The data about the clinical features of probands and the pattern of
      transmission of ADHD among relatives found little evidence for the validity of
      subthreshold ADHD among such subjects, who reported a lifetime history of some
      symptoms that never met DSM-IV's threshold for diagnosis. In contrast, the
      results suggested that late-onset adult ADHD is valid and that DSM-IV's age-at
      onset criterion is too stringent.

PMID- 17012683
TI  - Impact of psychometrically defined deficits of executive functioning in adults
      with attention deficit hyperactivity disorder.
AB  - OBJECTIVE: The association between deficits in executive functioning and
      functional outcomes was examined among adults with attention deficit
      hyperactivity disorder (ADHD). METHOD: Subjects were adults who did (N=213) and
      did not (N=145) meet DSM-IV criteria for ADHD. The authors defined having
      deficits in executive functioning as having at least two measures of executive
      functioning with scores 1.5 standard deviations below those of matched comparison
      subjects. RESULTS: Significantly more adults with ADHD had deficits of executive
      functioning than comparison subjects. Deficits of executive functioning were
      associated with lower academic achievement, irrespective of ADHD status. Subjects
      with ADHD with deficits of executive functioning had a significantly lower
      socioeconomic status and a significant functional morbidity beyond the diagnosis
      of ADHD alone. CONCLUSIONS: Psychometrically defined deficits of executive
      functioning may help identify a subgroup of adults with ADHD at high risk for
      occupational and academic underachievement. More efforts are needed to identify
      cost-effective approaches to screen individuals with ADHD for deficits of
      executive functioning.

PMID- 17012684
TI  - Analysis of the patient-therapist relationship in dynamic psychotherapy: an
      experimental study of transference interpretations.
AB  - OBJECTIVE: The purpose of this study was to measure the effects of transference
      interpretations (the assumed core active ingredient) in dynamic psychotherapy,
      using an experimental design. METHOD: One hundred patients were randomly assigned
      to two groups. One group received dynamic psychotherapy over 1 year, with a
      moderate level of transference interpretations, while the other group received
      dynamic psychotherapy with no transference interpretations. The most common axis
      I disorders were depression and anxiety disorders. Forty-six patients fulfilled
      the general criteria for personality disorder. Seven experienced psychotherapists
      treated patients in both groups. Five full sessions from each treatment were
      rated by two evaluators with process measures in order to document treatment
      integrity. Outcome variables were the Psychodynamic Functioning Scales, Inventory
      of Interpersonal Problems Scale-Circumplex version, Global Assessment of
      Functioning Scale, and Symptom Checklist-90-R. Quality of Object Relations Scale
      (lifelong pattern) and personality disorders were preselected as possible
      moderators of treatment effects. Change was assessed using linear-mixed models.
      Clinically significant change was also calculated. RESULTS: The authors could not
      demonstrate differential treatment effects between the groups. However, the
      moderator analyses showed that transference interpretations were more helpful for
      patients with a lifelong history of less mature object relations. Small negative
      effects were observed for patients with mature object relations. CONCLUSIONS: The
      authors could not show differences in average effectiveness between treatments.
      However, the moderator analyses indicated that treatment worked through different
      active ingredients for different patients. Contrary to common expectation,
      patients with poor object relations profited more from therapy with transference
      interpretations than from therapy with no transference interpretations.

PMID- 17012685
TI  - Brain dopamine d1 receptors in twins discordant for schizophrenia.
AB  - OBJECTIVE: It has been suggested that deficits in higher-order cognitive
      functions serve as intermediate phenotypic indicators of genetic vulnerability to
      schizophrenia. The dopamine hypothesis of schizophrenia postulates that
      insufficiency of dopamine transmission in the prefrontal cortex contributes to
      the cognitive deficits observed in patients with the disease, and there is robust
      empirical evidence for a central role of prefrontal cortex dopamine D(1)
      receptors in working memory functions. METHOD: The authors examined the genetic
      and nongenetic effects on D(1) receptor binding in schizophrenia by studying
      monozygotic and dizygotic twin pairs discordant for schizophrenia as well as
      healthy comparison twins using positron emission tomography (PET) and the D(1)
      receptor antagonist ligand [(11)C]SCH 23390. Performance on neuropsychological
      tests sensitive to frontal lobe functioning was evaluated. RESULTS: High D(1)
      receptor density in the medial prefrontal cortex, superior temporal gyrus, and
      heteromodal association cortex (angular gyrus) was associated with increasing
      genetic risk for schizophrenia (comparison twins < unaffected dizygotic co-twins
      < unaffected monozygotic co-twins). Medicated schizophrenia patients demonstrated
      a widespread reduction in D(1) receptor binding when compared with the unaffected
      co-twin, and higher doses of antipsychotics were associated with lower D(1)
      receptor binding in the frontotemporal regions. CONCLUSIONS: This study
      demonstrated an association between genetic risk for schizophrenia and
      alterations in cortical D(1) receptor binding, an observation that has
      implications for future studies of the molecular genetics of schizophrenia. In
      addition, the data indicate a widespread reduction of D(1) receptor binding in
      medicated schizophrenia patients, supporting a link between antipsychotic drug
      action and dopamine D(1) receptor down-regulation.

PMID- 17012686
TI  - Familiality of polarity at illness onset in bipolar affective disorder.
AB  - OBJECTIVE: Bipolar affective disorder is clinically heterogeneous, and clinical
      features that run in families may help define more homogeneous phenotypes. The
      authors sought to establish whether polarity at illness onset, which is related
      to severity and course, is a familial feature of bipolar affective disorder.
      METHOD: The authors studied 971 subjects from 507 families ascertained through
      sibling pairs with bipolar I or schizoaffective bipolar disorder. Self-reported
      ages at onset of mania and major depression were used to code polarity at onset
      as manic, major depressive, or both (mania and major depression in the same onset
      year). Familial clustering was estimated by using mixed-effects regression
      analysis, and the relationship between polarity at onset and several other
      clinical features was assessed. As a preliminary test of genetic validity, the
      authors assessed the impact of polarity at onset on genetic linkage findings
      previously detected in this sample. RESULTS: Polarity at onset was significantly
      familial in this sample. This largely reflected relative pairs concordant for
      mania at onset, which occurred significantly more frequently than would be
      expected by chance. Mania at onset substantially increased the genetic linkage
      signal on chromosome 16p (maximum lod score=4.5) but had no effect on linkage to
      chromosome 6q. Mania at onset occurred at a later age on average than major
      depression at onset and was less likely to be complicated by panic attacks or
      alcoholism. CONCLUSIONS: Polarity at illness onset is a familial feature of
      bipolar affective disorder and is associated with important clinical indicators,
      which may help define more homogeneous subtypes of bipolar affective disorder.

PMID- 17012687
TI  - Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of
      linkage to 10q22.3.
AB  - OBJECTIVE: Genome-wide linkage analyses of schizophrenia have identified several
      regions that may harbor schizophrenia susceptibility genes, but given the complex
      etiology of the disorder, it is unlikely that all susceptibility regions have
      been detected. To address this issue, the authors ascertained 606 Han Chinese
      families comprising 1,234 affected members. METHOD: Probands with schizophrenia
      were recruited from six data collection field research centers in Taiwan. Each
      proband underwent a diagnostic screen with supplemental medical records and a
      semistructured interview. Following this screen, the authors administered the
      Mandarin Chinese version of the Diagnostic Interview for Genetic Studies. Best
      estimate final diagnoses were made by two board-certified psychiatrists. The
      genotyping was conducted by the Center for Inherited Disease Research, with 386
      markers spaced at an average of 9-centimorgan (cM) intervals. Empirical
      simulations were generated to determine genome-wide significance. RESULTS: The
      authors found five regions with nonparametric linkage z scores 2.0 or greater.
      These were the following: 2.08 was reached for D1S551 (113.7) cM at 1p31.1 and
      2.31 for D2S410 (125.2 cM) at 2q14.1; 2.00 was reached for D4S2361 (93.5 cM) at
      4q21.23, and 2.07 for D15S1012 (36 cM) at 15q14, the largest nonparametric
      linkage z score was 2.88 for D10S2327 (100.92 cM) at 10q22.3. CONCLUSIONS: Our
      10q22.3 finding at 100.9 cM is consistent with a previously reported
      nonparametric linkage score of 4.27 at 107.2 cM on chromosome 10, although it did
      not attain genome-wide significance in this study.

PMID- 17012688
TI  - Identification of the Slynar gene (AY070435) and related brain expressed
      sequences as a candidate gene for susceptibility to affective disorders through
      allelic and haplotypic association with bipolar disorder on chromosome 12q24.
AB  - OBJECTIVE: Three linkage studies of bipolar disorder have implicated chromosome
      12q24.3, with significant lod scores of over 3.00. Several other linkage studies
      have found lod scores between 2.00 and 3.00. In order to identify which gene on
      this chromosome is responsible, the authors carried out tests of allelic
      association with bipolar disorder in order to fine map an affective disorder
      susceptibility gene. METHOD: DNA samples from 681 bipolar disorder patients and
      570 comparison subjects from Denmark and the United Kingdom were genotyped with
      markers close to the region at which the authors had found maximum linkage in
      previous studies. RESULTS: Single marker allelic association was found with four
      markers in the Danish cohort. Seven markers in exactly the same region were then
      found to show significant allelic association in the U.K. cohort. Tests of
      haplotypic association were also significant, confirming the single marker
      allelic associations. CONCLUSIONS: These positive fine mapping results validate
      earlier linkage studies and implicate a 278-kilobase region of chromosome 12 that
      contributes to the etiology of bipolar disorder. Several brain transcripts are
      transcribed from sequences in the region. The main candidate gene has no known
      function but is found in human brain cDNA and is homologous to a Macaque brain
      cDNA. Sequencing of expressed sequences and control regions in the area should
      identify etiological base pair changes that increase susceptibility to bipolar
      disorder.

PMID- 17012689
TI  - Posttraumatic stress disorder and depression in battle-injured soldiers.
AB  - OBJECTIVE: This study examined rates, predictors, and course of probable
      posttraumatic stress disorder (PTSD) and depression among seriously injured
      soldiers during and following hospitalization. METHOD: The patients were 613 U.S.
      soldiers hospitalized following serious combat injury. Standardized screening
      instruments were administered 1, 4, and 7 months following injury; 243 soldiers
      completed all three assessments. Cross-sectional and longitudinal analyses of
      risk factors were performed. PTSD was assessed with the PTSD Checklist;
      depression was assessed with the Patient Health Questionnaire. Combat exposure,
      deployment length, and severity of physical problems were also assessed. RESULTS:
      At 1 month, 4.2% of the soldiers had probable PTSD and 4.4% had depression; at 4
      months, 12.2% had PTSD and 8.9% had depression; at 7 months, 12.0% had PTSD and
      9.3% had depression. In the longitudinal cohort, 78.8% of those positive for PTSD
      or depression at 7 months screened negative for both conditions at 1 month. High
      levels of physical problems at 1 month were significantly predictive of PTSD
      (odds ratio=9.1) and depression at 7 months (odds ratio=5.7) when the analysis
      controlled for demographic variables, combat exposure, and duration of
      deployment. Physical problem severity at 1 month was also associated with PTSD
      and depression severity at 7 months after control for 1-month PTSD and depression
      severity, demographic variables, combat exposure, and deployment length.
      CONCLUSIONS: Early severity of physical problems was strongly associated with
      later PTSD or depression. The majority of soldiers with PTSD or depression at 7
      months did not meet criteria for either condition at 1 month.

PMID- 17012690
TI  - Lack of ventral striatal response to positive stimuli in depressed versus normal
      subjects.
AB  - OBJECTIVE: Most of the functional neuroimaging studies of depression have focused
      primarily on the resting state or responses to negatively valenced stimuli.
      However, depression consists not only of an accentuation of negative affective
      processing but of an inability to experience pleasure or positive motivation. The
      authors tested the hypothesis that depressed subjects would show less activation
      than healthy comparison subjects, in response to positive stimuli, in ventral
      striatal regions associated with processing of reward and positive stimuli.
      METHOD: Positive, negative, and neutral words were presented to 10 unmedicated
      depressed patients and 12 healthy comparison subjects in the context of a 3T
      functional magnetic resonance imaging (MRI) paradigm. Image processing and
      analysis were performed using statistical parametric mapping with a mixed-effects
      model. Significant differences in neural responses were assessed, examining
      group, condition, and interaction effects of interest within the context of a
      general linear model. RESULTS: Relative to comparison subjects, depressed
      patients demonstrated significantly less bilateral ventral striatal activation to
      positive stimuli, correlating with decreased interest/pleasure in and performance
      of activities. They also displayed decreased activation to positive stimuli in a
      dorsomedial frontal region associated with processing of self-related stimuli.
      Responses of depressed subjects to negative stimuli were consistent with the
      growing literature on frontolimbic dysfunction in depression. CONCLUSIONS: This
      finding 1) supports a pathophysiological model of depression that includes
      reward/motivational pathway dysfunction, 2) suggests a contributing neural
      substrate of the inability to experience pleasure or engage in rewarding
      activities, 3) provides greater specification of abnormalities of basal ganglia
      function in depression, and 4) may help guide treatment approaches.

PMID- 17012692
TI  - Psychophysiological evidence of altered neural synchronization in cannabis use:
      relationship to schizotypy.
AB  - OBJECTIVE: Cannabis use may produce neurophysiological disturbances similar to
      those observed in schizophrenia, particularly in relation to altered neural
      synchronization. Therefore, the current experiment examined the effect of
      cannabis use on EEG neural synchronization using the auditory steady-state evoked
      potential. METHOD: Auditory steady-state evoked potentials were assessed using
      varying rates of stimulation (auditory click-trains of 20, 30, 40 Hz) in current
      cannabis users (N=17) and drug-naive comparison subjects (N=16). EEG spectral
      power and signal-to-noise ratio at each stimulation frequency were compared
      between groups. RESULTS: Cannabis users showed decreased EEG power and signal-to
      noise ratio at the stimulation frequency of 20 Hz. In addition, current cannabis
      users demonstrated increased schizotypal personality characteristics as assessed
      with the Schizotypal Personality Questionnaire, which positively correlated with
      total years of cannabis use. Finally, within the cannabis group, 20-Hz power
      values were negatively correlated with Schizotypal Personality Questionnaire
      scores. CONCLUSIONS: These data provide evidence for neural synchronization and
      early-stage sensory processing deficits in cannabis use. This finding, along with
      the observed increased rates of schizotypy in cannabis users, adds support for a
      cannabinoid link to schizophrenia spectrum disorders.

PMID- 17012691
TI  - Reduction of cancer-specific thought intrusions and anxiety symptoms with a
      stress management intervention among women undergoing treatment for breast
      cancer.
AB  - OBJECTIVE: After surgery for breast cancer, many women experience anxiety
      relating to the cancer that can adversely affect quality of life and emotional
      functioning during the year postsurgery. Symptoms such as intrusive thoughts may
      be ameliorated during this period with a structured, group-based cognitive
      behavior intervention. METHOD: A 10-week group cognitive behavior stress
      management intervention that included anxiety reduction (relaxation training),
      cognitive restructuring, and coping skills training was tested among 199 women
      newly treated for stage 0-III breast cancer. They were then followed for 1 year
      after recruitment. RESULTS: The intervention reduced reports of thought
      intrusion, interviewer ratings of anxiety, and emotional distress across 1 year
      significantly more than was seen with the control condition. The beneficial
      effects were maintained well past the completion of adjuvant therapy.
      CONCLUSIONS: Structured, group-based cognitive behavior stress management may
      ameliorate cancer-related anxiety during active medical treatment for breast
      cancer and for 1 year following treatment. Group-based cognitive behavior stress
      management is a clinically useful adjunct to offer to women treated for breast
      cancer.

PMID- 17012693
TI  - Estimated prevalence of compulsive buying behavior in the United States.
AB  - OBJECTIVE: Compulsive buying (uncontrolled urges to buy, with resulting
      significant adverse consequences) has been estimated to affect from 1.8% to 16%
      of the adult U.S. population. To the authors' knowledge, no study has used a
      large general population sample to estimate its prevalence. METHOD: The authors
      conducted a random sample, national household telephone survey in the spring and
      summer of 2004 and interviewed 2,513 adults. The interviews addressed buying
      attitudes and behaviors, their consequences, and the respondents' financial and
      demographic data. The authors used a clinically validated screening instrument,
      the Compulsive Buying Scale, to classify respondents as either compulsive buyers
      or not. RESULTS: The rate of response was 56.3%, which compares favorably with
      rates in federal national health surveys. The cooperation rate was 97.6%.
      Respondents included a higher percentage of women and people ages 55 and older
      than the U.S. adult population. The estimated point prevalence of compulsive
      buying among respondents was 5.8% (by gender: 6.0% for women, 5.5% for men). The
      gender-adjusted prevalence rate was 5.8%. Compared with other respondents,
      compulsive buyers were younger, and a greater proportion reported incomes under
      50,000 US dollars. They exhibited more maladaptive responses on most consumer
      behavior measures and were more than four times less likely to pay off credit
      card balances in full. CONCLUSIONS: A study using clinically valid interviews is
      needed to evaluate these results. The emotional and functional toll of compulsive
      buying and the frequency of comorbid psychiatric disorders suggests that studies
      of treatments and social interventions are warranted.

PMID- 17012694
TI  - Capacity of persons with mental retardation to consent to participate in
      randomized clinical trials.
AB  - OBJECTIVE: Adults with mental retardation have histories of cognitive and
      adaptive deficits posing unique ethical challenges for research consent
      assessment. This study examined the capacity of persons with mental retardation
      to consent to participate in randomized clinical trials. METHOD: A total of 150
      adults (50 each with mild and moderate mental retardation and 50 comparison
      subjects without mental retardation) responded to a set of consent questions for
      a hypothetical randomized clinical trial testing a medication for aggressive
      disorders. Intelligence, adaptive behavior, medical treatment history, and
      consent history were evaluated. Univariate and multivariate methods were used to
      compare performance across and within groups. RESULTS: Comparison subjects scored
      significantly higher on measures of consent capacity than participants with mild
      mental retardation, who scored higher than those with moderate mental
      retardation. Most subjects with mental retardation were able to make a
      participation choice, and many understood research methods and appreciated the
      protagonist's disorder and the consequences of participation. Almost half of
      those with mild mental retardation understood human subject protections.
      Performance was weakest on understanding the purpose of research and reasoning
      about whether to participate, suggesting vulnerability to the therapeutic
      misconception. Psychiatric and experiential factors did not predict consent
      capacity. CONCLUSIONS: While adults with mental retardation as a group showed
      consent deficits, many attained consent capacity scores comparable to those of
      comparison subjects. Investigators should consider individual differences and a
      consent format suited to deficits in language, memory, and attention before
      restricting consent opportunities for persons with mental retardation.

PMID- 17012695
TI  - Hyperlipidemia following treatment with antipsychotic medications.
AB  - OBJECTIVE: This study attempted to estimate the relative risk of developing
      hyperlipidemia after treatment with antipsychotics in relation to no
      antipsychotic treatment. METHOD: A matched case-control analysis was performed
      with pharmacy and claims data from California Medicaid (Medi-Cal). Patients were
      excluded if they were treated for medical disorders or prescribed medications
      known to increase their risk of hyperlipidemia. Cases were ages 18 to 64 years
      with schizophrenia, major depression, bipolar disorder, or other affective
      psychoses and incident hyperlipidemia. Cases were matched to up to six control
      subjects by age, sex, race, and psychiatric diagnosis. Both groups were
      prescribed either no antipsychotic medication or had two or more prescriptions
      for one and only one antipsychotic medication during the 60 days prior to the
      first indication of hyperlipidemia (cases) or matched index date (controls) in
      the billing record. Conditional logistic regressions were used to derive odds
      ratios and 95% confidence intervals (95% CIs) of each antipsychotic medication in
      relation to no antipsychotic medication. RESULTS: A total of 13,133 incident
      cases of hyperlipidemia were matched to 72,140 control subjects. As compared with
      no antipsychotic medication, treatment with clozapine (odds ratio: 1.82, 95% CI:
      1.61-2.05), risperidone (odds ratio: 1.53, 95% CI: 1.43-1.64), quetiapine (odds
      ratio: 1.52, 95% CI: 1.40-1.65), olanzapine (odds ratio: 1.56, 95% CI: 1.47
      1.67), ziprasidone (odds ratio: 1.40, 95% CI: 1.19-1.65), and first-generation
      antipsychotics (odds ratio: 1.26, 95% CI: 1.14-1.39), but not aripiprazole (odds
      ratio: 1.19, 95% CI: 0.94-1.52) was associated with a significant increase in
      risk of incident hyperlipidemia. CONCLUSIONS: These findings suggest that most
      commonly prescribed antipsychotic medications increase the risk of developing
      hyperlipidemia in patients with schizophrenia or mood disorders.

PMID- 17012696
TI  - Effect of 5-HT1A receptor gene polymorphism on negative and depressive symptom
      response to antipsychotic treatment of drug-naive psychotic patients.
AB  - OBJECTIVE: The serotonin 5-HT(1A) receptor may modulate some of the negative,
      cognitive, and affective symptoms of schizophrenia and is a potential target of
      action of some antipsychotic drugs. A functional polymorphism in the promoter
      region of the 5-HT(1A) receptor gene is associated with depression and suicidal
      behavior. The authors sought to determine whether this polymorphism influences
      symptom response to antipsychotic drug treatment. METHOD: Sixty-three drug-naive
      patients with first-episode psychosis who were genotyped for the -1019C/G
      polymorphism were recruited for this study and received standard care. The
      Positive and Negative Syndrome Scale and the Calgary Depression Scale were used
      to monitor symptom changes over 3 months. RESULTS: The polymorphism was
      associated with, and accounted for much of the variance in, changes in negative
      and depressive symptoms but not positive symptoms. CONCLUSIONS: These findings
      identify an important genetic factor predicting much of the response in negative
      and depressive symptoms to antipsychotic drug treatment.

PMID- 17012697
TI  - Increased expression of activity-dependent genes in cerebellar glutamatergic
      neurons of patients with schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to evaluate the functional state of
      glutamatergic neurons in the cerebellar cortex of patients with schizophrenia.
      METHOD: The authors measured messenger ribonucleic acid (mRNA) levels of three
      activity-dependent genes expressed by glutamatergic neurons in the cerebellar
      cortex (GAP-43, BDNF, and GABA OLE_LINK2>(A)-delta subunit) in the tissues of 14
      patients with schizophrenia and 14 matched nonpsychiatric comparison subjects.
      Since its level of expression does not change in response to neuronal activity,
      gamma-aminobutyric acid(A)-alpha6 subunit mRNA was used as a control. RESULTS:
      The levels of GAP-43 and BDNF mRNAs were significantly elevated in patients with
      schizophrenia, and a similar finding was observed for GABA(A)-delta mRNA. In
      contrast, the levels of the GABA(A)-alpha6 subunit mRNA, which is expressed in
      cerebellar granule cells in an activity-independent manner, did not differ from
      comparison subjects. CONCLUSIONS: These results suggest that glutamatergic
      neurons may be hyperactive in the cerebellar cortices of patients with
      schizophrenia.

PMID- 17012698
TI  - Episodic memory performance predicted by the 2bp deletion in exon 6 of the "alpha
      7-like" nicotinic receptor subunit gene.
AB  - OBJECTIVE: There is evidence of linkage between chromosome 15q14 and the P50
      auditory evoked response, a heritable neuropsychological marker associated with
      increased risk of schizophrenia. Chromosome 15q14 harbors the alpha-7 nicotinic
      receptor subunit gene (CHRNA7) and a hybrid gene of unknown function (CHRFAM7A).
      CHRNA7 is involved in memory formation, a core dysfunction in schizophrenia. The
      authors set out to determine if this locus is associated with memory dysfunction
      in schizophrenia. METHOD: A 2bp deletion in exon 6 of CHRFAM7A, which disrupts
      the hybrid gene and has previously been associated with P50 deficit, was
      genotyped in 251 individuals from the Maudsley Family Study of schizophrenia.
      Episodic memory function was assessed using the Wechsler Memory Scale. RESULTS:
      Significant associations were identified with delayed recall and percentage
      retained, with the presence of the deletion predicting worse performance.
      CONCLUSIONS: These observations indicate that episodic memory function is a
      schizophrenia endophenotype and implicate the CHRFAM7A/CHRNA7 locus in modulating
      its function.

PMID- 17012699
TI  - The human homolog of the QKI gene affected in the severe dysmyelination "quaking"
      mouse phenotype: downregulated in multiple brain regions in schizophrenia.
AB  - OBJECTIVE: The authors sought to understand the origins of oligodendrocyte/myelin
      gene expression abnormalities in the brains of persons with schizophrenia.
      METHOD: Twelve cortical regions (Brodmann's areas 8, 10, 44, 46, 23/31, 24/32,
      20, 21, 22, 36/28, 7, and 17) and three noncortical regions (caudate,
      hippocampus, and putamen) of 16 elderly schizophrenia patients and 14 matched
      comparison subjects were examined using 450 separate microarrays. The mRNA levels
      of QKI and its isoforms were then measured in a larger cohort by using
      quantitative real-time polymerase chain reaction (qPCR) in the cingulate cortex
      of schizophrenia subjects and matched comparison subjects. RESULTS: Expression of
      QKI mRNA was decreased in seven cortical regions and the hippocampus in the
      schizophrenia subjects. QKI gene expression deficits detected by microarray were
      validated by qPCR in the cingulate cortex, where the expression of isoforms QKI
      5, QKI-6, and QKI-7 were profoundly perturbed in schizophrenia. CONCLUSIONS:
      Since QKI plays a fundamental role in oligodendrocyte differentiation and in
      myelination, its underexpression may be pivotal to, and upstream of, other myelin
      associated gene expression abnormalities in schizophrenia. Given the role of QKI
      in determination of oligodendrocyte fate, these results not only confirm
      oligodendrocyte-related gene expression abnormalities in schizophrenia but
      suggest that the physiology of glial progenitor cells may be altered in
      schizophrenia.

PMID- 17012700
TI  - Does olanzapine have any antidepressant effect?

PMID- 17012701
TI  - Ethical concerns regarding olanzapine versus placebo in patients prodromally
      symptomatic for psychosis.

PMID- 17012702
TI  - Observed effects of creatine monohydrate in a patient with depression and
      fibromyalgia.

PMID- 17012703
TI  - Antisocial personality disorder as a confounder in PTSD and substance use
      disorders.

PMID- 17012704
TI  - Lingual lesions with orally disintegrating risperidone.

PMID- 17012705
TI  - The internet as collateral informant.

PMID- 17012706
TI  - The Tower of Babel and health outcomes.

PMID- 17012707
TI  - Temporomandibular disorders.

PMID- 17012708
TI  - Dental education.

PMID- 17012709
TI  - More about TMD and SEMG.

PMID- 17012710
TI  - Securing the future.

PMID- 17012712
TI  - Informed consent.

PMID- 17012713
TI  - Dr. Robert J. Gorlin, world-renowned oral pathologist, dies at 83.

PMID- 17012716
TI  - Is there an association between occlusion and periodontal destruction?: Yes-
      occlusal forces can contribute to periodontal destruction.

PMID- 17012717
TI  - Is there an association between occlusion and periodontal destruction?: Only in
      limited circumstances does occlusal force contribute to periodontal disease
      progression.

PMID- 17012718
TI  - Sialoendoscopy: A new approach to salivary gland obstructive pathology.
AB  - BACKGROUND: During the last 13 years, there has been a growing interest in and
      use of minimally invasive treatment techniques. Salivary gland endoscopes provide
      an accurate means of diagnosing and providing minimally invasive surgical
      treatment for salivary gland diseases. METHODS: The authors review the relevant
      literature and provide the history of sialoendoscopy. They also report on the
      treatment methods they use, including instruments and techniques, and their
      experiences. RESULTS: The authors' overall success rate for parotid endoscopic
      sialolithotomy is 86 percent, and their overall success rate for submandibular
      endoscopic sialolithotomy is 89 percent. Their success rate for treating
      strictures is 81 percent. CLINICAL IMPLICATIONS: The endoscopic technique opens
      new horizons in the field of salivary gland diseases. Salivary gland stones and
      sialadenitis no longer are absolute indications for sialadenectomy. Owing to
      growing experience and surgical skills, new endoscopic techniques are in clinical
      use, and there is constant improvement in endoscopic treatment success rates.
      CONCLUSIONS: Sialoendoscopy is a promising new method for use in the diagnosis,
      treatment and postoperative management of sialadenitis, sialolithiasis and other
      obstructive salivary gland diseases.

PMID- 17012719
TI  - A two-year clinical evaluation of pit and fissure sealants placed with and
      without air abrasion pretreatment in teenagers.
AB  - BACKGROUND: Long-term retention of pit and fissure sealants is essential for
      their success. The aim of this study was to compare the retention rates of
      sealants placed with acid-etching and air abrasion followed by acid etching.
      METHODS: Sixteen subjects aged 16 and 17 years were included in the study. Using
      a half-mouth design, the authors performed fissure preparation with phosphoric
      acid gel on randomly assigned maxillary and mandibular permanent premolars and
      molars from one side of the mouth (Group I) and performed air abrasion followed
      by acid etching on the contralateral side of the mouth (Group II). The authors
      applied sealant material on 162 teeth, and they evaluated the sealants as
      complete retention, partial loss or total loss at six, 12 and 24 months. RESULTS:
      While fissure sealant retention rates were not significantly different for the
      two techniques at six months (P = .97), the retention rates for the teeth in
      Group II were significantly higher at 12 (P = .025) and 24 months (P = .002).
      Molar retention rates were significantly less than those for premolars at each
      evaluation period (P < .05). CONCLUSION: The sealant retention rates at 12 and 24
      months were higher in Group II (air abrasion followed by acid etching). CLINICAL
      IMPLICATIONS: As air abrasion followed by acid etching resulted in significantly
      higher sealant retention rates, this method could be a good choice for fissure
      preparation before sealant placement for long-term success.

PMID- 17012720
TI  - The antimicrobial effect of a triclosan/copolymer dentifrice on oral
      microorganisms in vivo.
AB  - BACKGROUND: The authors compared the in vivo antimicrobial effects on
      microorganisms from dental plaque, saliva and the tongue in subjects who used a
      triclosan/copolymer dentifrice and a fluoride dentifrice (control). METHODS: The
      authors assigned 15 subjects randomly to the control dentifrice or the
      triclosan/copolymer dentifrice for twice-daily use for one week. They collected
      samples of plaque, saliva and tongue scrapings six and 12 hours after the final
      brushing. They analyzed colony-forming units of Veillonella species, Fusobacteria
      species, total cultivable anaerobes and hydrogen sulfide (H(2)S)-producing
      bacteria. A one-week washout followed. The authors repeated the protocol with the
      second dentifrice. RESULTS: The results showed no differences at baseline.
      Significant reductions (88 to 96 percent) in oral anaerobic bacteria were
      observed in the triclosan/copolymer group six and 12 hours after brushing
      compared with the control group (P = .001). Fusobacteria decreased by 77 to 92
      percent and Veillonella decreased by 84 to 89 percent six and 12 hours after
      brushing in the triclosan/copolymer group versus the control group. The
      triclosan/copolymer group also demonstrated a significant decrease in H(2)S
      producing bacteria six and 12 hours after brushing (74 to 85 percent) (P = .001).
      CONCLUSIONS: Brushing with the triclosan/copolymer dentifrice resulted in
      significant reductions in microorganisms from the three sites compared with the
      control dentifrice. CLINICAL IMPLICATIONS: The triclosan/copolymer dentifrice
      produced sustained effects on oral bacteria for 12 hours.

PMID- 17012722
TI  - The effect of disinfectants and line cleaners on the release of mercury from
      amalgam.
AB  - BACKGROUND: Dental practices use disinfectants or line cleaners to flush dental
      unit wastewater lines to minimize odor generation, remove solid waste particles
      and remove biofilms in dental unit water lines (DUWLs). METHODS: The authors
      evaluated 47 disinfectants or line cleaners for their potential to release
      mercury from amalgam waste. They prepared each product concentration according to
      the manufacturer's recommendations and gently agitated it along with one amalgam
      specimen for 24 hours. They filtered the combined decanted liquid and rinse and
      analyzed it for mercury using modified U.S. Environmental Protection Agency
      method 245.1. RESULTS: Six preparations released significantly more mercury from
      amalgam (about 17 to 340 times) than did the deionized water control (P < .001).
      The amount of mercury released by the other disinfectants/line cleaners was not
      statistically different from that released by the control. The pH values of all
      preparations ranged from 1.76 to 12.35. CONCLUSION AND CLINICAL IMPLICATIONS:
      This study and other published reports have demonstrated that preparations
      containing chlorine release more mercury from amalgam than did some other
      products and the deionized water control. As a result, the use of these products
      is not recommended for treating dental office wastewater lines or DUWLs.

PMID- 17012721
TI  - In vitro microtensile bond strength of four adhesives tested at the gingival and
      pulpal walls of Class II restorations.
AB  - BACKGROUND: The authors compared the microtensile bond strength of teeth restored
      with four adhesives at the gingival and pulpal cavity walls of Class II resin
      based composite restorations. METHODS: Five pairs of extracted third molars
      received two Class II preparations/restorations in each tooth. The authors
      randomly assigned each preparation to one of four adhesive groups: Adper
      Scotchbond Multipurpose Dental Adhesive (SBMP) (3M ESPE, St. Paul, Minn.),
      Clearfil SE Bond (CFSE) (Kuraray America, New York City), Prime & Bond NT (PBNT)
      (Dentsply Caulk, Milford, Del.) and PQ1 (Ultradent, South Jordan, Utah). They
      restored the teeth and obtained microtensile specimens from each cavity wall.
      Specimens were tested on a testing machine until they failed. RESULTS: The mean
      (+/- standard deviation) bond strengths (in megapascals) were as follows: SBMP
      (pulpal), 36.4 (17.2); SBMP (gingival), 29.7 (15.3); CFSE (pulpal), 50.8 (13.6);
      CFSE (gingival), 50.2 (14.0); PBNT (pulpal), 38.3 (19.2); PBNT (gingival), 38.9
      (17.7); PQ1 (pulpal), 58.7 (8.7); and PQ1 (gingival), 54.5 (18.5). A two-way
      analysis of variance found an adhesive effect (P < .001) but no location effect
      (P >.05). CONCLUSIONS: PQ1 and CFSE performed the best. The results showed no
      significant difference in microtensile bond strength at the gingival wall versus
      the pulpal wall. CLINICAL IMPLICATIONS: Under in vitro conditions, a total-etch
      ethanol-based adhesive (PQ1) failed cohesively more often than did the other
      adhesives tested.

PMID- 17012723
TI  - Marketing the dental practice: eight steps toward success.
AB  - BACKGROUND: The authors provide a suggested framework for completing a
      comprehensive evaluation of practice processes and routines. Their approach
      focuses on improving the professional image of dentists and the methods they use
      to market themselves. CONCLUSIONS: A practice can benefit by implementing a
      program to understand the strengths and weaknesses of the practice and how these
      strengths and weaknesses affect patients' experiences. A word-of-mouth marketing
      campaign relies on the cultivation of opinion leaders, but opinion leaders cannot
      be cultivated until they have been identified. Dental practice marketing
      campaigns cannot be based on assumptions; they must be based on facts. Practice
      Implications. Improving relationships with patients will lead to increased
      patient retention, reduced marketing costs and greater personal satisfaction. By
      focusing on strengths, clinicians will improve patients' experiences in the
      dental office.

PMID- 17012724
TI  - An analysis of the contribution of a patient-based component to a clinical
      licensure examination.
AB  - BACKGROUND: The validity and reliability of high-stakes examinations such as
      those used by national, regional and state or provincial dental boards are under
      intense scrutiny by candidates, dental schools, dental educators, dental
      associations, and state or provincial dental boards. METHODS: The authors
      followed the progress of 1,063 candidates from nonaccredited dental programs who
      began the National Dental Examining Board of Canada's (NDEB) clinical
      examinations between January 1996 and November 1999 through the administration of
      the examination's final component in December 2003 examine the utility and
      validity of the patient-based component of the examination process. RESULTS: The
      results showed that the first three components of the examination were effective
      in screening out candidates who were not adequately prepared to take the patient
      based component. Only 12 (1.1 percent) of the candidates failed the maximum
      allowed three attempts to pass the patient-based component. CONCLUSIONS: The
      results demonstrated that the patient-based component did not contribute to the
      overall examination validity or decision making and did not prevent candidates
      from obtaining certification. PRACTICE IMPLICATIONS: Owing to this lack of
      utility, the associated costs and ethical concerns, NDEB eliminated the patient
      based component of the examination and replaced it with the requirement to
      complete an accredited, qualifying/degree completion dental program followed by
      completion of NDEB's written and objective structured clinical examination
      components.

PMID- 17012725
TI  - Implant therapy versus endodontic therapy.

PMID- 17012726
TI  - Dental malpractice claims: percentages and procedures.

PMID- 17012727
TI  - What are my ethical obligations in handling after-hours calls from patients of
      other dentists in my community?

PMID- 17012728
TI  - For the dental patient. Dental radiographs: a diagnostic tool.

PMID- 17012729
TI  - The oral-systemic disease connection. An update for the practicing dentist.

PMID- 17012730
TI  - Exploring the relationship between periodontal disease and pregnancy
      complications.
AB  - BACKGROUND: Increasing evidence suggests that maternal gingivitis and
      periodontitis may be a risk factor for preterm birth and other adverse pregnancy
      outcomes. TYPES OF STUDIES REVIEWED: To clarify the possible mechanisms behind
      the association between periodontal disease and preterm delivery, the authors
      reviewed studies of the effect of infection with periodontal pathogens in animal
      models on pregnancy outcomes including fetal growth, placental structural
      abnormalities and neonatal health. After the first report, in 1996, of a
      potential association between maternal periodontal disease and delivery of a
      preterm/low-birth-weight infant in humans, many case control and prospective
      studies were published. This review summarizes these, as well as early studies
      involving periodontal intervention to reduce risk. RESULTS: Although there are
      some conflicting findings and potential problems regarding uncontrolled
      underlying risk factors, most of the clinical studies indicate a positive
      correlation between periodontal disease and preterm birth. Recent studies also
      have shown that there are microbiologic and immunological findings that strongly
      support the association. The studies indicate that periodontal infection can lead
      to placental-fetal exposure and, when coupled with a fetal inflammatory response,
      can lead to preterm delivery. Data from animal studies raise the possibility that
      maternal periodontal infections also may have adverse long-term effects on the
      infant's development. CLINICAL IMPLICATIONS: Education for patients and health
      care providers regarding the biological plausibility of the association and the
      potential risks is indicated, but there is insufficient evidence at this time for
      health care policy recommendations to provide maternal periodontal treatments for
      the purpose of reducing the risk of adverse pregnancy outcomes.

PMID- 17012731
TI  - Periodontal infections and cardiovascular disease: the heart of the matter.
AB  - BACKGROUND: Oral infection models have emerged as useful tools to study the
      hypothesis that infection is a cardiovascular disease (CVD) risk factor.
      Periodontal infections are a leading culprit, with studies reporting associations
      between periodontal disease and CVD. The results, however, have varied, and it
      often is unclear what conclusions can be drawn from these data. SUMMARY: An
      association exists between periodontal disease and CVD. It is unknown, however,
      whether this relationship is causal or coincidental. Early studies predominantly
      used nonspecific clinical and radiographic definitions of periodontal disease as
      surrogates for infectious exposure. While most studies demonstrated positive
      associations between periodontal disease and CVD, not all studies were positive,
      and substantial variations in results were evident. More recent studies have
      enhanced the specificity of infectious exposure definitions by measuring systemic
      antibodies to selected periodontal pathogens or by directly measuring and
      quantifying oral microbiota from subgingival dental plaque. Results from these
      studies have shown positive associations between periodontal disease and CVD.
      CONCLUSIONS: Evidence continues to support an association among periodontal
      infections, atherosclerosis and vascular disease. Ongoing observational and
      focused pilot intervention studies may inform the design of large-scale clinical
      intervention studies. Recommending periodontal treatment for the prevention of
      atherosclerotic CVD is not warranted based on scientific evidence. Periodontal
      treatment must be recommended on the basis of the value of its benefits for the
      oral health of patients, recognizing that patients are not healthy without good
      oral health. However, the emergence of periodontal infections as a potential risk
      factor for CVD is leading to a convergence in oral and medical care that can only
      benefit the patients and public health.

PMID- 17012732
TI  - Pneumonia in nonambulatory patients. The role of oral bacteria and oral hygiene.
AB  - BACKGROUND: Considerable evidence exists to support a relationship between poor
      oral health, the oral microflora and bacterial pneumonia, especially ventilator
      associated pneumonia in institutionalized patients. Teeth or dentures have
      nonshedding surfaces on which oral biofilms (that is, dental plaque) form that
      are susceptible to colonization by respiratory pathogens. Subsequent aspiration
      of respiratory pathogens shed from oral biofilms into the lower airway increases
      the risk of developing a lung infection. In addition, patients may aspirate
      inflammatory products from inflamed periodontal tissues into the lower airway,
      contributing to lung insult. TYPES OF STUDIES REVIEWED: The author reviewed
      laboratory studies, clinical trials and review articles. CONCLUSIONS: A number of
      studies have shown that the mouth can be colonized by respiratory pathogens and
      serve as a reservoir for these organisms. Other studies have demonstrated that
      oral interventions aimed at controlling or reducing oral biofilms can reduce the
      risk of pneumonia in high-risk populations. Taken together, the evidence is
      substantial that improved oral hygiene may prevent pneumonia in vulnerable
      patients. CLINICAL IMPLICATIONS: Institution of rigorous oral hygiene regimens
      for hospitalized patients and long-term-care residents may reduce the risk of
      developing pneumonia.

PMID- 17012733
TI  - Periodontal disease and diabetes. A two-way street.
AB  - BACKGROUND: The association between diabetes and inflammatory periodontal
      diseases has been studied extensively for more than 50 years. The author reviews
      the bidirectional relationships between diabetes and periodontal diseases.
      CONCLUSIONS: A large evidence base suggests that diabetes is associated with an
      increased prevalence, extent and severity of gingivitis and periodontitis.
      Furthermore, numerous mechanisms have been elucidated to explain the impact of
      diabetes on the periodontium. While inflammation plays an obvious role in
      periodontal diseases, evidence in the medical literature also supports the role
      of inflammation as a major component in the pathogenesis of diabetes and diabetic
      complications. Research suggests that, as an infectious process with a prominent
      inflammatory component, periodontal disease can adversely affect the metabolic
      control of diabetes. Conversely, treatment of periodontal disease and reduction
      of oral inflammation may have a positive effect on the diabetic condition,
      although evidence for this remains somewhat equivocal. CLINICAL IMPLICATIONS:
      Patients with diabetes who have periodontal disease have two chronic conditions,
      each of which may affect the other, and both of which require frequent
      professional evaluations, in-depth patient education and consistent educational
      reinforcement by health care providers.

PMID- 17012734
TI  - Challenges in interpreting study results: the conflict between appearance and
      reality.
AB  - BACKGROUND: Many studies investigating the relationship between periodontal
      disease and systemic diseases have been reported; the majority of these have been
      epidemiologic (or observational) studies. The purpose of this article is to help
      readers understand the strengths and limitations of epidemiology for the purpose
      of being better able to interpret these studies. FINDINGS: Epidemiologic studies
      include retrospective case-control studies and prospective cohort studies. While
      these studies cannot prove causality, they can provide strong evidence for and
      show the strength of an association between a disease and putative causative
      factors. Randomized controlled trials (RCTs) are used to test therapeutic and
      preventive measures and can provide presumptive evidence of disease causation in
      certain circumstances. Each of these study types has limitations that can distort
      the study results and, therefore, should be considered in study design and
      analysis. CONCLUSIONS AND CLINICAL IMPLICATIONS: Epidemiologic studies conducted
      to date suggest an association between periodontal disease and a number of
      systemic diseases. However, the strength and nature of this association are not
      yet clear, because in some cases it might result from confounding by smoking or
      other variables. Additional well-designed observational studies and future RCTs
      should increase our understanding of the actual relationship between periodontal
      and systemic diseases.

PMID- 17012736
TI  - Brief report: Increasing children's safe pedestrian behaviors through simple
      skills training.
AB  - OBJECTIVES: Hundreds of American children are killed and thousands more injured
      annually as pedestrians. Simple and effective interventions targeting behavioral
      changes in children are needed. METHODS: The present study tested a simple, skill
      based training method for increasing safe pedestrian behaviors. Eighty-five
      children ages 5-8 participated. RESULTS: Children behaved more safely following
      training, indicating very brief training can produce at least short-term
      improvements in pedestrian behaviors. CONCLUSIONS: Results are discussed with
      regard to the involvement of parents in the practical application of a simple
      training procedure and future directions for pedestrian interventions.

PMID- 17012737
TI  - Brief report: Behavioral risk factors for youth soccer (football) injury.
AB  - OBJECTIVES: By most reports, soccer (football) is among the most played and most
      popular sports in the world. This study prospectively examined behavioral risk
      factors for youth soccer injury. METHOD: Sixty 11- and 12-year-old boys who
      played on six teams in a suburban recreational soccer league were followed over
      the course of a season. Six predictors were assessed prior to the start of the
      season via self-report measures from coaches, parents, and the players
      themselves: inhibition, aggression, risk-taking, skill, experience playing
      soccer, and physical size. All games were videotaped, and tapes were reviewed to
      record players' collisions with other players, fouls, falls during the course of
      play, and injuries. RESULTS: Greater skill and less experience playing soccer
      best predicted injury risk. Inhibition, aggression, and risk-taking did not
      emerge as predictors. CONCLUSION: Results are discussed with respect to previous
      research in youth sport and general pediatric injury risk.

PMID- 17012738
TI  - Brief report: Television viewing and risk for attention problems in preschool
      children.
AB  - OBJECTIVES: This study examined whether high levels of television viewing are
      associated with attention problems and hyperactivity in preschool children.
      METHODS: Parent and teacher ratings of inattention, hyperactivity and
      impulsivity, objectively measured activity level, and parental estimation of
      early television exposure were collected for a sample of preschool children.
      Separate linear regression analyses were conducted with parent and teacher
      behavioral ratings and objectively assessed activity level as outcome variables.
      RESULTS: Results indicated that after controlling for demographic factors (i.e.,
      age, sex, and SES), television exposure accounted for a significant proportion of
      the variance in teacher ratings of inattentive/hyperactive behaviors, as well as
      objectively measured activity level. CONCLUSIONS: These findings partially
      replicate those from a recent, highly publicized study indicating a correlation
      between television exposure and attention-deficit/hyperactivity disorder (ADHD)
      associated behaviors. However, it remains unclear as to whether elevated levels
      of television viewing are the cause or result of ADHD symptoms.

PMID- 17012739
TI  - Acute renal failure in a patient with West Nile viral encephalitis.

PMID- 17012740
TI  - Wall-yielding properties of cell walls from elongating cucumber hypocotyls in
      relation to the action of expansin.
AB  - The wall-yielding properties of cell walls were examined using frozen-thawed and
      pressed segments (FTPs) obtained from the elongation zones of cucumber hypocotyls
      with a newly developed programmable creep meter. The rate of wall extension
      characteristically changed depending on both tension and pH. By treatment of the
      FTPs with acid, the yield tension (y) was shifted downward and the extensibility
      (phi) was increased. However, the downward shift of y was greatly suppressed and
      the increase in phi was partly inhibited in boiled FTPs. The boiled FTPs
      reconstituted with expansin fully recovered the acid-induced downward y shift as
      well as the increase in phi. Even under the tension below y, wall extension took
      place pH dependently. Such extension was markedly slower (low-rate extension)
      than that under the tension above y (high-rate extension). At a higher
      concentration (8 M), urea markedly inhibited the creep ascribable to the
      inhibition of the acid-induced downward y shift and increase in phi. Moderate
      concentrations (2 M) of urea promoted wall creep pH dependently. The promotion
      was equivalent to a 0.5 decrease in pH. The promotion of creep by 2 M urea was
      observed in boiled FTPs reconstituted with expansin but not in boiled FTPs. These
      findings indicated that the acid-facilitated creep was controlled by y as well as
      in cucumber cell walls. However, y and phi might be inseparable and mutually
      related parameters because the curve of the stress extension rate (SER) showed a
      gradual change from the low-rate extension to the high-rate extension. Expansin
      played a role in pH-dependent regulation of both y and phi. The physiological
      meaning of the pH-dependent regulation of wall creep under different creep
      tensions is also discussed with reference to a performance chart obtained from
      the SER curves.

PMID- 17012741
TI  - Changes in plant mitochondrial electron transport alter cellular levels of
      reactive oxygen species and susceptibility to cell death signaling molecules.
AB  - Transgenic tobacco (Nicotiana tabacum) lacking mitochondrial alternative oxidase
      (AOX) have been compared with wild-type (Wt) tobacco using two different systems,
      either suspension cell cultures or leaves. In both systems, a lack of AOX was
      accompanied by an increase in some anti-oxidant defenses, consistent with the
      hypothesis that a lack of AOX increases the mitochondrial generation of reactive
      oxygen species (ROS). In most cases, this increase in anti-oxidant defenses could
      more than offset the presumed increased rate of ROS generation, resulting
      paradoxically in a lower steady-state level of ROS than was found in Wt leaves or
      suspension cells. We also found that the amount of cell death induced by
      salicylic acid or nitric oxide correlated strongly with the level of ROS
      (irrespective of the level of AOX), while death induced by azide was dependent
      upon the presence or absence of AOX. These results suggest that susceptibility to
      cell death by signaling molecules (salicylic acid and nitric oxide) is dependent
      upon the steady-state cellular level of ROS and that AOX levels clearly
      contribute to this steady state, perhaps by influencing the rate of mitochondrial
      generated ROS and hence the cellular level of anti-oxidant defenses.

PMID- 17012742
TI  - Mammalian lin-7 stabilizes polarity protein complexes.
AB  - Mammalian Lin-7 forms a complex with several proteins, including PALS1, that have
      a role in polarity determination in epithelial cells. In this study we have found
      that loss of Lin-7 protein from the polarized epithelial cell line Madin-Darby
      canine kidney II by small hairpin RNA results in defects in tight junction
      formation as indicated by lowered transepithelial electrical resistance and
      mislocalization of the tight junction protein ZO-1 after calcium switch. The
      knock down of Lin-7 also resulted in the loss of expression of several Lin-7
      binding partners, including PALS1 and the polarity protein PATJ. The effects of
      Lin-7 knock down were rescued by the exogenous expression of murine Lin-7
      constructs that contained the L27 domain, but not the PDZ domain alone.
      Furthermore, exogenously expressed PALS1, but not other Lin-7 binding partners,
      also rescued the effects of Lin-7 knock down, including the restoration of PATJ
      protein in rescued cell lines. Finally, the effects of Lin-7 knock down appeared
      to be due to instability of PALS1 protein in the absence of Lin-7, as indicated
      by an increased rate of PALS1 protein degradation. Taken together, these results
      indicate that Lin-7 functions in tight junction formation by stabilizing its
      membrane-associated guanylate kinase binding partner PALS1.

PMID- 17012743
TI  - Purification of a NifEN protein complex that contains bound molybdenum and a FeMo
      Co precursor from an Azotobacter vinelandii DeltanifHDK strain.
AB  - The NifEN protein complex serves as a molecular scaffold where some of the steps
      for the assembly of the iron-molybdenum cofactor (FeMo-co) of nitrogenase take
      place. A His-tagged version of the NifEN complex has been previously purified and
      shown to carry two identical [4Fe-4S] clusters of unknown function and a [Fe-S]
      containing FeMo-co precursor. We have improved the purification of the his-NifEN
      protein from a DeltanifHDK strain of Azotobacter vinelandii and have found that
      the amounts of iron and molybdenum within NifEN were significantly higher than
      those reported previously. In an in vitro FeMo-co synthesis system with purified
      components, the NifEN protein served as a source of both molybdenum and a [Fe-S]
      containing FeMo-co precursor, showing significant FeMo-co synthesis activity in
      the absence of externally added molybdate. Thus, the NifEN scaffold protein,
      purified from DeltanifHDK background, contained the Nif-Bco-derived Fe-S cluster
      and molybdenum, although these FeMo-co constituents were present at different
      levels within the protein complex.

PMID- 17012744
TI  - Effects of the N-terminal domains of myosin binding protein-C in an in vitro
      motility assay: Evidence for long-lived cross-bridges.
AB  - Myosin binding protein-C (MyBP-C) is a thick-filament protein whose precise
      function within the sarcomere is not known. However, recent evidence from cMyBP-C
      knock-out mice that lack MyBP-C in the heart suggest that cMyBP-C normally slows
      cross-bridge cycling rates and reduces myocyte power output. To investigate
      possible mechanisms by which cMyBP-C limits cross-bridge cycling kinetics we
      assessed effects of recombinant N-terminal domains of MyBP-C on the ability of
      heavy meromyosin (HMM) to support movement of actin filaments using in vitro
      motility assays. Here we show that N-terminal domains of cMyBP-C containing the
      MyBP-C "motif," a sequence of approximately 110 amino acids, which is conserved
      across all MyBP-C isoforms, reduced actin filament velocity under conditions
      where filaments are maximally activated (i.e. either in the absence of thin
      filament regulatory proteins or in the presence of troponin and tropomyosin and
      high [Ca2+]). By contrast, under conditions where thin filament sliding speed is
      submaximal (i.e. in the presence of troponin and tropomyosin and low [Ca2+]),
      proteins containing the motif increased filament speed. Recombinant N-terminal
      proteins also bound to F-actin and inhibited acto-HMM ATPase rates in solution.
      The results suggest that N-terminal domains of MyBP-C slow cross-bridge cycling
      kinetics by reducing rates of cross-bridge detachment.

PMID- 17012745
TI  - Tropomodulin 3 binds to actin monomers.
AB  - Regulation of the actin cytoskeleton by filament capping proteins is critical to
      myriad dynamic cellular functions. The ability of these proteins to bind both
      filaments as well as monomers is often central to their cellular functions. The
      ubiquitous pointed end capping protein Tmod3 (tropomodulin 3) acts as a negative
      regulator of cell migration, yet mechanisms behind its cellular functions are not
      understood. Analysis of Tmod3 effects on kinetics of actin polymerization and
      steady state monomer levels revealed that Tmod3, unlike previously characterized
      tropomodulins, sequesters actin monomers with an affinity similar to its affinity
      for capping pointed ends. Furthermore, Tmod3 is found bound to actin in high
      speed supernatant cytosolic extracts, suggesting that Tmod3 can bind to monomers
      in the context of other cytosolic monomer binding proteins. The Tmod3-actin
      complex can be efficiently cross-linked with 1-ethyl-3
      (dimethylaminopropyl)carbodiimide/N-hydroxylsulfosuccinimide in a 1:1 complex.
      Subsequent tryptic digestion and liquid chromatography/tandem mass spectrometry
      revealed two binding interfaces on actin, one distinct from other actin monomer
      binding proteins, and two potential binding sites in Tmod3, which are independent
      of the previously characterized leucine-rich repeat structure involved in pointed
      end capping. These data suggest that the Tmod3 isoform may regulate actin
      dynamics differently in cells than the previously described tropomodulin
      isoforms.

PMID- 17012746
TI  - Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation,
      and motility of epidermal keratinocytes.
AB  - A novel family of focal adhesion proteins, the kindlins, is involved in
      attachment of the actin cytoskeleton to the plasma membrane and in integrin
      mediated cellular processes. Deficiency of kindlin-1, as a result of loss-of
      function mutations in the KIND1 gene, causes Kindler syndrome, an autosomal
      recessive genodermatosis characterized by skin blistering, progressive skin
      atrophy, photosensitivity and, occasionally, carcinogenesis. Here we
      characterized authentic and recombinantly expressed kindlin-1 and show that it is
      localized in basal epidermal keratinocytes in a polar fashion, close to the cell
      surface facing the basement membrane, in the areas between the hemidesmosomes. We
      identified two forms of kindlin-1 in keratinocytes, with apparent molecular
      masses of 78 and 74 kDa, corresponding to phosphorylated and desphosphorylated
      forms of the protein. In kindlin-1-deficient skin, basal keratinocytes show
      multiple abnormalities: cell polarity is lost, proliferation is strongly reduced,
      and several cells undergo apoptosis. In vitro, deficiency of kindlin-1 in
      keratinocytes leads to strongly reduced cell proliferation, decreased adhesion,
      undirected motility, and intense protrusion activity of the plasma membrane.
      Taken together, these results show that kindlin-1 plays a role in keratinocyte
      adhesion, polarization, proliferation, and migration. It is involved in
      organization and anchorage of the actin cytoskeleton to integrin-associated
      signaling platforms.

PMID- 17012747
TI  - Kinetic and mechanistic basis of the nonprocessive Kinesin-3 motor NcKin3.
AB  - Kinesin-3 motors have been shown to transport cellular cargo along microtubules
      and to function according to mechanisms that differ from the conventional hand
      over-hand mechanism. To find out whether the mechanisms described for Kif1A and
      CeUnc104 cover the full spectrum of Kinesin-3 motors, we characterize here
      NcKin3, a novel member of the Kinesin-3 family that localizes to mitochondria of
      ascomycetes. We show that NcKin3 does not move in a K-loop-dependent way as Kif1A
      or in a cluster-dependent way as CeUnc104. Its in vitro gliding velocity ranges
      between 0.30 and 0.64 mum/s and correlates positively with motor density. The
      processivity index (k(bi,ratio)) of approximately 3 reveals that not more than
      three ATP molecules are hydrolyzed per productive microtubule encounter. The
      NcKin3 duty ratio of 0.03 indicates that the motor spends only a minute fraction
      of the ATPase cycle attached to the filament. Unlike other Kinesin-3 family
      members, NcKin3 forms stable dimers, but only one subunit releases ADP in a
      microtubule-dependent fashion. Together, these data exclude a processive hand
      over-hand mechanism of movement and suggest a power-stroke mechanism where
      nucleotide-dependent structural changes in a single motor domain lead to
      displacement of the motor along the filament. Thus, NcKin3 is the first plus end
      directed kinesin motor that is dimeric but moves in a nonprocessive fashion to
      its destination.

PMID- 17012748
TI  - Human myosin III is a motor having an extremely high affinity for actin.
AB  - Myosin IIIA is expressed in photoreceptor cells and thought to play a critical
      role in phototransduction processes, yet its function on a molecular basis is
      largely unknown. Here we clarified the kinetic mechanism of the ATPase cycle of
      human myosin IIIA. The steady-state ATPase activity was markedly activated
      approximately 10-fold with very low actin concentration. The rate of ADP off from
      actomyosin IIIA was 10 times greater than the overall cycling rate, thus not a
      rate-determining step. The rate constant of the ATP hydrolysis step of the actin
      dissociated form was very slow, but the rate was markedly accelerated by actin
      binding. The dissociation constant of the ATP-bound form of myosin IIIA from
      actin is submicromolar, which agrees well with the low K(actin). These results
      indicate that ATP hydrolysis predominantly takes place in the actin-bound form
      for actomyosin IIIA ATPase reaction. The obtained K(actin) was much lower than
      the previously reported one, and we found that the autophosphorylation of myosin
      IIIA dramatically increased the K(actin), whereas the V(max) was unchanged. Our
      kinetic model indicates that both the actin-attached hydrolysis and the P(i)
      release steps determine the overall cycle rate of the dephosphorylated form.
      Although the stable steady-state intermediates of actomyosin IIIA ATPase reaction
      are not typical strong actin-binding intermediates, the affinity of the stable
      intermediates for actin is much higher than conventional weak actin binding
      forms. The present results suggest that myosin IIIA can spend a majority of its
      ATP hydrolysis cycling time on actin.

PMID- 17012749
TI  - Opposing roles for Akt1 and Akt2 in Rac/Pak signaling and cell migration.
AB  - The Akt/PKB isoforms have different roles in animals, with Akt2 primarily
      regulating metabolic signaling and Akt1 regulating growth and survival. Here we
      show distinct roles for Akt1 and Akt2 in mouse embryo fibroblast cell migration
      and regulation of the cytoskeleton. Akt1-deficient cells responded poorly to
      platelet-derived growth factor while Akt2-deficient cells had a dramatically
      enhanced response, resulting in a substantial increase in dorsal ruffling.
      Swapping domains between Akt1 and Akt2 demonstrated that the N-terminal region
      containing the pleckstrin homology domain and a linker region distinguishes the
      two isoforms, while the catalytic domains are interchangeable. Akt2 knock-out
      cells also migrated faster than wild-type cells, especially through extracellular
      matrix (ECM), while Akt1 knock-out cells migrated more slowly than wild-type
      cells. Consistently, Akt2 knock-out cells had elevated Pak1 and Rac activities,
      suggesting that Akt2 inhibits Rac and Pak1. Both Akt2 and Akt1 associated in
      complexes with Pak1, but only Akt2 inhibited Pak1 in kinase assays, suggesting an
      underlying molecular basis for the different cellular phenotypes. Together these
      data provide evidence for an unexpected functional link between Akt2 and Pak1
      that opposes the actions of Akt1 on cell migration.

PMID- 17012750
TI  - Thematic review series: systems biology approaches to metabolic and
      cardiovascular disorders. Reverse engineering gene networks to identify key
      drivers of complex disease phenotypes.
AB  - Diseases such as obesity, diabetes, and atherosclerosis result from multiple
      genetic and environmental factors, and importantly, interactions between genetic
      and environmental factors. Identifying susceptibility genes for these diseases
      using genetic and genomic technologies is accelerating, and the expectation over
      the next several years is that a number of genes will be identified for common
      diseases. However, the identification of single genes for disease has limited
      utility, given that diseases do not originate in complex systems from single gene
      changes. Further, the identification of single genes for disease may not lead
      directly to genes that can be targeted for therapeutic intervention. Therefore,
      uncovering single genes for disease in isolation of the broader network of
      molecular interactions in which they operate will generally limit the overall
      utility of such discoveries. Several integrative approaches have been developed
      and applied to reconstructing networks. Here we review several of these
      approaches that involve integrating genetic, expression, and clinical data to
      elucidate networks underlying disease. Networks reconstructed from these data
      provide a richer context in which to interpret associations between genes and
      disease. Therefore, these networks can lead to defining pathways underlying
      disease more objectively and to identifying biomarkers and more-robust points for
      therapeutic intervention.

PMID- 17012751
TI  - Cholestanol metabolism in patients with cerebrotendinous xanthomatosis:
      absorption, turnover, and tissue deposition.
AB  - To study the metabolism of cholestanol in patients with cerebrotendinous
      xanthomatosis (CTX), we measured the cholestanol absorption, the cholesterol and
      cholestanol turnover, and the tissue content of sterols in two patients.
      Cholestanol absorption was approximately 5.0%. The rapid exchangeable pool of
      cholestanol was 233 mg, and the total exchangeable pool was 752 mg. The
      production rate of cholestanol in pool A was 39 mg/day. [4-14C]cholestanol was
      detected in the xanthomas, but neither [4-14C]cholestanol nor [4-14C]cholesterol
      was detected in peripheral nerves biopsied at 49 and 97 days after [4
      14C]cholesterol given intravenously. Of the 18 tissues analyzed at biopsy and
      autopsy, the cholestanol content varied from 0.09 mg/g in psoas muscle to 76 mg/g
      in a cerebellar xanthoma. With the assumption that the cholestanol-to-cholesterol
      ratio is 1.0, the relative cholestanol-to-cholesterol ratio varied from 1.0 in
      plasma and liver to 30.0 in the cerebellar xanthoma; cholestanol was especially
      high in nerve tissue. Our data indicate that CTX patients absorb cholestanol from
      the diet. They have a higher than normal cholestanol production rate. Cholestanol
      was derived from cholesterol. In CTX patients, the blood-brain barrier was intact
      to the passage of [4-14C]cholesterol and [4-14C]cholestanol. The deposition of
      large amounts of cholestanol (up to 30% of total sterols in cerebellum) in nerve
      tissues must have an important role in the neurological symptoms in CTX patients.
      In view of the intact blood-brain barrier, several other explanations for the
      large amounts of cholestanol in the brain were postulated.

PMID- 17012752
TI  - Analysis of peptide/MHC-induced TCR downregulation: deciphering the triggering
      kinetics.
AB  - The interaction of T-lymphocytes with antigen-presenting cells displaying a small
      number of specific peptide/major histocompatibility complexes results in the
      downregulation of a large number of T-cell receptors (TCR), suggesting serial TCR
      triggering. However, the details of TCR downregulation are controversial. In
      particular, the level of comodulation of nonengaged TCR reported by different
      authors ranges from essentially none to considerable levels. Here, we address
      this controversy using complementary experimental and mathematical techniques. We
      find that TCR downregulation is very rapid during the first 2-4 min after T-cell
      antigen-presenting cells contact formation. After this phase, TCR downregulation
      proceeds at a relatively slow rate. Statistical and computational analyses show
      that this pronounced change in downregulation kinetics is compatible with the
      notion of initial serial triggering of clustered TCR followed by serial
      triggering of individual TCR. We further propose a compatible mechanism for
      concurrent triggering of multiple TCR by a single peptide/major
      histocompatibility complex. We provide a unified picture of productive TCR
      engagement and downregulation in which TCR triggering characteristics evolve from
      an initial cooperative phase to a sustained phase of signal accumulation.

PMID- 17012754
TI  - Simulation of molecular crowding effects on an Alzheimer's beta-amyloid peptide.
AB  - Fibril formation by the Alzheimer's beta-amyloid (Abeta) peptide in brain tissue
      is integral to the Alzheimer's disease pathology. Understanding the
      conformational properties and the mechanisms triggering aggregation of the Abeta
      peptides, at an atomic level of detail, is of crucial importance for the design
      of effective therapeutic agents against this disease. In this work, the
      conformational transitions and dynamic properties of an amyloidogenic peptide
      fragment (Abeta10-35) were studied by molecular dynamics simulations in systems
      modeling infinite dilution and the presence of macromolecular crowding agents
      (CA). The model system consists of the peptide described with an atomistic force
      field, the CA represented by inert, quasi-hard spheres and a continuum solvent
      model. This combined model allowed the simulations to be extended to 100 ns each.
      Simulations were carried out starting from a completely extended structure, a
      beta-strand structure, and four nuclear magnetic resonance structures in dilute
      aqueous solution. For all structures, two additional simulations were performed
      that included the inert CA in the solution and occupied approx 30 and 40% of the
      volume, respectively. For two of the nuclear magnetic resonance structures,
      additional simulations were carried out with 35% volume fraction of CA to further
      examine the diffusive behavior of the peptide. The peptide adopted a collapsed
      coil conformation in all simulations. The results of the simulations in dilute
      solution showed reasonable qualitative agreement with experimental and other
      simulation results, whereas the presence of volume excluding agents resulted in
      some distinct changes in properties (e.g., an increase in the appearance of
      transient beta-structure or decreases in diffusivity with increasing CA
      concentration). At the same time, internal motion such as order parameters or
      atomic root mean square fluctuations showed less systematic responses to volume
      exclusion.

PMID- 17012753
TI  - Chronotropic response of cultured neonatal rat ventricular myocytes to short-term
      fluid shear.
AB  - Ventricular myocytes are continuously exposed to fluid shear in vivo by relative
      movement of laminar sheets and adjacent cells. Preliminary observations have
      shown that neonatal myocytes respond to fluid shear by increasing their beating
      rate, which could have an arrhythmogenic effect under elevated shear conditions.
      The objective of this study is to investigate the characteristics of the fluid
      shear response in cultured myocytes and to study selected potential mechanisms.
      Cultured neonatal rat ventricular myocytes that were spontaneously beating were
      subjected to low shear rates (5-50/s) in a fluid flow chamber using standard
      culture medium. The beating rate was measured from digital microscopic
      recordings. The myocytes reacted to low shear rates by a graded and reversible
      increase in their spontaneous beating rate of up to 500%. The response to shear
      was substantially attenuated in the presence of the beta-adrenergic agonist
      isoproterenol (by 86+/-8%), as well as after incubation with integrin-blocking
      RGD peptides (by 92+/-8%). The results suggest that the beta-adrenergic signaling
      pathway and integrin activation, which are known to interact, may play an
      important role in the response mechanism.

PMID- 17012755
TI  - The reliability of relative anion-cation permeabilities deduced from reversal
      (dilution) potential measurements in ion channel studies.
AB  - Measurements of anion-cation permeability ratios (e.g., PCl/PNa) are most readily
      made by measuring changes in zero-current reversal potential when the salt
      concentration on one side of the membrane (e.g., external NaCl) is decreased.
      This is particularly useful for measuring changes in ion selectivity in wild-type
      and mutant channels, such as those of the ligand-gated ion channel superfamily,
      and has shown that many of these channels have a significant permeability to
      counter-ions. One Brownian dynamics study of ion permeation through such narrow
      ion channels failed to observe such counter-ion movement, although later, another
      Brownian dynamics study did observe counter-ion movement through simulations of
      the same channels. The question has been raised as to the reliability of such
      reversal potential measurements for determining permeability ratios, particularly
      given the use of an equation such as the Goldman-Hodgkin-Katz (GHK) equation,
      which is often used to calculate such ratios. A new derivation of the GHK
      equation in terms of activity coefficients is also included. The application of
      irreversible thermodynamics will be shown to qualitatively support the
      reliability of such experimental anion-cation permeability values derived from
      reversal potential measurements. It will then be shown that for such zero-current
      situations, different electrodiffusion models, with very different underlying
      assumptions, produce almost identical relative permeabilities (and reversal
      potentials). Finally, the results of the two Brownian dynamics simulation studies
      and the relationship between reversal potentials and relative permeability will
      be discussed.

PMID- 17012756
TI  - Caveolae and caveolae constituents in mechanosensing: effect of modeled
      microgravity on cultured human endothelial cells.
AB  - Studies in modeled microgravity or during orbital space flights have clearly
      demonstrated that endothelial cell physiology is strongly affected by the
      reduction of gravity. Nevertheless, the molecular mechanisms by which endothelial
      cells may sense gravity force remain unclear. We previously hypothesized that
      endothelial cell caveolae could be a mechanosensing system involved in
      hypergravity adaptation of human endothelial cells. In this study, we analyzed
      the effect on the physiology of human umbilical vein endothelial cell monolayers
      of short exposure to modeled microgravity (24-48 h) obtained by clinorotation.
      For this purpose, we evaluated the levels of compounds, such as nitric oxide and
      prostacyclin, involved in vascular tone regulation and synthesized starting from
      caveolae-related enzymes. Furthermore, we examined posttranslational
      modifications of Caveolin (Cav)-1 induced by simulated microgravity. The results
      we collected clearly indicated that short microgravity exposure strongly affected
      endothelial nitric oxide synthase activity associated with Cav-1 (Tyr 14)
      phosphorylation, without modifying the angiogenic response of human umbilical
      vein endothelial cells. We propose here that one of the early molecular
      mechanisms responsible for gravity sensing of endothelium involves endothelial
      cell caveolae and Cav-1 phosphorylation.

PMID- 17012757
TI  - What is a desirable statistical energy function for proteins and how can it be
      obtained?
AB  - Can one obtain a physical energy function for proteins from statistical analysis
      of protein structures? A direct answer to this question is likely "no." Aless
      demanding question is whether one can produce a statistical energy function that
      has the desirable features of a physical-based energy function. Such a desirable
      energy function would be founded on a physical basis with few or no adjustable
      parameters, reproduce the known physical characters of amino acid residues, be
      mostly database independent and transferable, and, more importantly, reasonably
      accurate in various applications. In this review, we show how such a desirable
      energy function can be obtained via introducing a simple physical-based reference
      state called DFIRE (Distance-scaled, Finite, Ideal-gas REference state).

PMID- 17012758
TI  - RNA interference and ion channel physiology.
AB  - RNA interference (RNAi), through expression of small, double-stranded RNAs or
      short hairpin RNAs, produces sequence-specific mRNA degradation and decreased
      gene expression. Since its discovery in 1998 (Fire et al., 1998, Nature 391, 806
      811), RNAi has rapidly become one of the most widely used technologies for
      exploring gene function in eukaryotic cells. Although the topic of RNAi has been
      the subject of a large number of excellent reviews, the focus of this article is
      on its application to the study of ion channel physiology in animal cells. In
      this regard, RNAi has provided definitive identification of ion channel subtypes
      responsible for both basal and stimulated ion conduction across the plasma
      membrane of several cell types. The approach has been particularly effective in
      identifying and establishing the contribution of auxiliary subunits and
      regulatory proteins to the overall function of ion channel complexes. Moreover,
      selective knockdown of ion channel expression has been a valuable means of
      demonstrating roles in the development of specific cell domains and in the normal
      growth of certain cell types. In this review, a brief description of the general
      mechanism of RNAi is presented, followed by a discussion of some important
      considerations for the in vitro application of this technology and in producing
      transgenic animals as models for human disease. We then describe several examples
      of where RNAi has been used to investigate the physiological role of ion channels
      in cells from model organisms (Caenorhabditis elegans and Drosophila
      melanogaster) and in mammalian cells.

PMID- 17012759
TI  - Free radicals in biology and medicine: from inflammation to biotechnology.

PMID- 17012760
TI  - High resolution 1H NMR investigations of the oxidative consumption of salivary
      biomolecules by ozone: relevance to the therapeutic applications of this agent in
      clinical dentistry.
AB  - High resolution proton (1H) nuclear magnetic resonance (NMR) spectroscopy was
      employed to simultaneously evaluate the oxidising actions of ozone (O3) towards a
      wide range of salivary biomolecules in view of its applications in dental
      practices, which may serve as a viable and convenient means for the treatment of
      dental caries. Treatment of supernatants derived from unstimulated human saliva
      specimens (n=12) with O3 (4.48 mmol) revealed that this reactive oxygen species
      gave rise to the oxidative consumption of pyruvate (generating acetate and CO2 as
      products), lactate (to pyruvate and sequentially acetate and CO2), carbohydrates
      in general (a process generating formate), methionine (giving rise to its
      corresponding sulphoxide), and urate (to allantoin). Further, minor O3-induced
      modifications included the oxidation of trimethylamine and 3-D-hydroxybutyrate,
      the fragmentation of salivary glycosaminoglycans to NMR-detectable saccharide
      fragments, and the conversion of polyunsaturated fatty acids to their ozonides.
      Moreover, evidence for the ability of O3 to induce the release of selected low
      molecular-mass salivary biomolecules from macromolecular binding-sites was also
      obtained. Since many of the oxidation products detectable in O3-treated samples
      are identical to those arising from the attack of *OH radical on biofluid
      components, it appears that at least some of the modifications observed here are
      attributable to the latter oxidant (derived from O3*- generated from the single
      electron reduction of O3).

PMID- 17012761
TI  - Chemopreventive actions of polyphenolic compounds in cancer.
AB  - Oxidative stress and associated mechanisms involving inflammation, aberrant
      signaling pathways and gap junction intercellular communication is increasingly
      associated with the pathogenesis of various chronic degenerative disorders such
      as atherosclerosis, neurodegeneration and cancer. Consumption of fruits,
      vegetables and beverages like teas continues to be suggested to have the capacity
      to reduce the incidence of cancer. The bioactive compounds including phenolics
      may be responsible for the chemopreventive effects. While the free radical
      scavenging and antioxidant properties of phenolics are well established, emerging
      literature reports suggest that their chemopreventive effects may also be
      ascribed to their ability to modulate components of cell signaling pathways. This
      paper reviews the potential chemoprevention role of phenolics with a focus on
      cellular signal transduction mechanisms and prevention of gap junction
      intercellular communication relevant to cancer.

PMID- 17012762
TI  - Anti-mitotic properties of resveratrol analog (Z)-3,5,4'-trimethoxystilbene.
AB  - (Z)-3,5,4'-Trimethoxystilbene is a natural polyphenol present in five different
      plants, Virola cuspidata, Virola elongata, Centipeda minima, Schoenus nigricans
      and Rheum undulatum. This molecule was prepared in a three-step sequence in good
      overall yield. The isomerisation from the (E)- to (Z)-isomer is performed using
      UV irradiation. Biological investigations were conducted on a human colon cancer
      cell line (Caco-2) with anti-mitotic activities. Growth was completely arrested
      at an added 0.4 microM level of (Z)-3,5,4'-trimethoxystilbene. This agent is 100
      fold more active than resveratrol or (E)-3,5,4'-trihydroxystilbene, and the
      mechanism of this process involves an inhibition of tubulin polymerisation in a
      dose dependent manner.

PMID- 17012763
TI  - Thioredoxin-binding protein-2 (TBP-2): its potential roles in the aging process.
AB  - Thioredoxin (TRX) binding protein-2 (TBP-2), a negative regulator of TRX, is
      involved in intracellular redox regulation and cellular growth. The expression of
      TBP-2 is frequently lost in tumor cell lines and tissues, whereas the ectopic
      expression of TBP-2 suppresses cellular proliferation along with cell cycle
      arrest at the G1 phase. TBP-2 was also reported to be a cellular senescence
      associated gene. Besides the retardation of cellular growth, the reduction of
      white adipose, and alteration of the energy pathway are involved in several
      features of the aging process. We have generated TBP-2 genetically modified mice
      and found that TBP-2 is closely linked to lipid metabolism. Indeed, TBP-2 has
      been suggesting to be related to familial combined hyperlipidemia analyzed by a
      spontaneous mutant mouse strain. As lipid metabolism is one of the most primitive
      sources of energy production, we discussed the possible roles of TBP-2 in the
      regulation of energy utilization connected to the aging process.

PMID- 17012764
TI  - Enhanced cardiovascular function and energy level by a novel chromium (III)
      supplement.
AB  - The impetus for the novel Energy Formula (EF) which combines the niacin-bound
      chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera extracts
      (10.71%), caffeine (22.76%), D-ribose (10.71%) and selected amino acids such as
      phenylalanine, taurine and glutamine (55.37%) was based on the knowledge of the
      cardioprotective potentials of the Withania somnifera extract, caffeine and D
      ribose as well as their abilities to increase energy levels and the abilities of
      amino acids to increase the muscle mass and energy levels. The effect of oral
      supplementation of EF on the safety, myocardial energy levels and
      cardioprotective ability were investigated in an ischemic-reperfused myocardium
      model in both male and female Sprague-Dawley rats over 90 days trial period. At
      the completion of 90 days, the EF-treated male and female rats gained 9.4% and
      3.1% less body weights, respectively, as compared to their corresponding control
      groups. No significant difference was found in the levels of lipid peroxidation
      and activities of hepatic Aspartate transaminase, Alanine transaminase and
      Alkaline phosphatase in EF treatment when compared with control animals. The male
      and female rat hearts were subjected to 30 min of global ischemia followed by 2 h
      of reperfusion at 30 and 90 days of EF treatment. Cardiovascular functions
      including heart rate, coronary flow, aortic flow, dp/dt(max), left ventricular
      developed pressure (LVDP) and infarct size were monitored. The levels of
      myocardial adenosine triphosphate (ATP), creatine phosphate (CP), phospho
      adenosine monophosphate kinase (p-AMPK) levels, were analyzed at the end of 30
      and 90 days of treatment. Significant improvement was observed in all parameters
      in the EF treatment groups as compared to their corresponding controls. Thus the
      niacin-bound chromium (III) based energy formula is safe and effective supplement
      to boost energy levels and cardioprotection.

PMID- 17012765
TI  - Croton lobatus, an African medicinal plant: spectroscopic and chemical
      elucidation of its many constituents.
AB  - The chemical constituents of the African medicinal plant Croton lobatus were
      elucidated and characterised using 1D and 2D-NMR analysis and the application of
      the technique of High Resolution Electron Ionization Mass Spectrometry (HREIMS)
      and High Resolution Mass Spectrometry (HRMS). The novel triglyceride lobaceride
      or 3-((6Z,9Z)dodeca-6,9-dienoyloxy)-2-octanoyloxypropyl (6Z,9Z)dodeca-6,9
      dienoate, along with ten compounds were isolated from the stems and leaves of
      Croton lobatus.

PMID- 17012766
TI  - Assessment of the polyphenolic composition of the organic extracts of Mauritian
      black teas: a potential contributor to their antioxidant functions.
AB  - There is increasing interest in the emerging view that tea improves the
      antioxidant status in vivo and thereby helps to lower risk of certain types of
      cancer, coronary heart disease and stroke and its component biofactors could
      provide prophylactic potential for these diseases. The polyphenolic composition
      and the antioxidant properties of organic extracts (acetone/methanol) of
      Mauritian commercial black teas were evaluated. HPLC data of the individual
      compounds revealed remarkably high levels (+)-Catechin ((+)-C), (-)-epicatechin
      ((-)-EC), (-)-epicatechin 3-gallate ((-)-ECG), (-)-epigallocatechin ((-)-EGC), (
      )-epigallocatechin 3-gallate ((-)-EGCG) and gallic acid. Analysis of hydrolysed
      extracts indicated that quercetin was the dominant flavonol aglycone with traces
      of myricetin and kaempferol. Based on the Ferric Reducing Antioxidant Power
      (FRAP) and the Trolox Equivalent Antioxidant Capacity (TEAC) assays Extra tea
      from Bois Cheri exhibited the highest antioxidant potential. Linear regression
      analyses showed that the antioxidant capacities of the organic extracts are
      strongly influenced by total phenols (TEAC: r=0.95 and FRAP: r=0.96) and to a
      lesser extent by total proanthocyanidin and total flavonoid contents. Catechins
      and gallic acid seem to add up to the overall antioxidant capacity of black tea
      extracts. The fresh tea leaves had high levels of total phenols, total
      flavonoids, total proanthocyanidin and exhibited greater antioxidant potential
      when compared with black teas. Organic extracts of endemic teas represent useful
      source of phenolic antioxidants supplements for prophylactic use.

PMID- 17012767
TI  - Functional studies of an HIV-1 encoded glutathione peroxidase.
AB  - In an alternate reading frame overlapping the viral envelope gene, HIV-1 has been
      shown to encoded a truncated glutathione peroxidase (GPx) module. Essential
      active site residues of the catalytic core regions of mammalian GPx sequences are
      conserved in the putative viral GPx (vGPx, encoded by the env-fs gene). Cells
      transfected with an HIV-1 env-fs construct show up to a 100% increase in GPx
      enzyme activity, and are protected against the loss of mitochondrial
      transmembrane potential and subsequent cell death induced by exogenous oxidants
      or mitochondrial reactive oxygen species. An intact vGPx gene was observed to be
      more common in HIV-1-infected long-term non-progressors, as compared to HIV-1
      isolates from patients developing AIDS. An antioxidant/antiapoptotic protective
      role of the vGPx is also consistent with the observation that -1 frameshifting
      induced by the HIV-1 env-fs sequence AAAAAGA (which contains a potential "hungry"
      arginine codon, AGA) increases during arginine deficiency, which has been
      associated with increased oxidative stress. Under arginine-limited conditions,
      nitric oxide synthase generates superoxide, which rapidly combines with NO to
      form peroxynitrite, which can cause activated T-cells to undergo apoptosis. Thus,
      biosynthesis of the HIV-1 GPx as an adaptive response to low arginine conditions
      might delay oxidant-induced apoptotic cell death, providing an enhanced
      opportunity for viral replication.

PMID- 17012768
TI  - The thiol-based redox networks of pathogens: unexploited targets in the search
      for new drugs.
AB  - Hydroperoxide metabolism in diverse pathogens is reviewed under consideration of
      involved enzymes as potential drug targets. The common denominator of the
      peroxidase systems of Trypanosoma, Leishmania, Plasmodium, and Mycobacterium
      species is the use of NAD(P)H to reduce hydroperoxides including peroxynitrite
      via a flavin-containing disulfide reductase, a thioredoxin (Trx)-related protein
      and a peroxidase that operates with thiol catalysis. In Plasmodium falciparum,
      thioredoxin- and glutathione dependent systems appear to be linked via
      glutaredoxin and plasmoredoxin to terminal thioredoxin peroxidases belonging to
      both, the peroxiredoxin (Prx) and glutathione peroxidase (GPx) family. In
      Mycobacterium tuberculosis, a catalase-type peroxidase is complemented by the
      typical 2-C-Prx AhpC that, in contrast to most bacteria, is reduced by TrxC, and
      an atypical 2-C-Prx reduced by TrxB or C. A most complex variation of the scheme
      is found in trypanosomatids, where the unique redox metabolite trypanothione
      reduces the thioredoxin-related tryparedoxin, which fuels Prx- and GPx-type
      peroxidases as well as ribonucleotide reductase. In Trypanosoma brucei and
      Leishmania donovani the system has been shown to be essential for viability and
      virulence by inversed genetics. It is concluded that optimum efficacy can be
      expected from inhibitors of the most upstream components of the redox cascades.
      For trypanosomatids attractive validated drug targets are trypanothione reductase
      and trypanothione synthetase; for mycobacteria thioredoxin reductase appears most
      appealing, while in Plasmodium simultaneous inhibition of both the thioredoxin
      and the glutathione pathway appears advisable to avoid mutual substitution in co
      substrate supply to the peroxidases. Financial and organisational needs to
      translate the scientific progress into applicable drugs are discussed under
      consideration of the socio-economic impact of the addressed diseases.

PMID- 17012769
TI  - Determination of the illicit drug gamma-hydroxybutyrate (GHB) in human saliva and
      beverages by 1H NMR analysis.
AB  - High resolution 1H NMR spectroscopy has been employed to investigate the
      detection and quantification of the illicit "date-rape" drug gamma
      hydroxybutyrate (GHB) in both human saliva and a commonly-consumed low-alcohol
      beer product. Data acquired revealed that this multicomponent analytical
      technique provided unequivocal evidence for the detection of this agent by this
      technique in both of these matrices, i.e., all three of its resonances [those
      ascribable to the alpha-CH2 (t, delta=2.25 ppm), beta-CH2 (tt, delta=1.81 ppm)
      and gamma-CH2 (t, delta=3.61 ppm) group protons] were present in spectra acquired
      on human saliva, and two of these (the alpha- and beta-CH2 group signals) in the
      beverage product examined, the latter observation attributable to overlap of the
      gamma-CH2 1H resonance with those of carbohydrates. Since good linear calibration
      relationships between the intensities of each of the NMR-visible signals and
      added GHB concentration (the former normalised to that of an external 3
      trimethylsilyl [2,2,3,3-2H4]- propionate standard present in a coaxial NMR tube
      insert) were observed, this illicit drug is also readily quantifiable in such
      multicomponent samples. Our data demonstrate the advantages offered by this
      technique when applied to the analysis of illicit drugs in multicomponent sample
      matrices such as human biofluids and beverage products.

PMID- 17012770
TI  - Effects of quercetin and beta-carotene supplementation on azoxymethane-induced
      colon carcinogenesis and inflammatory responses in rats fed with high-fat diet
      rich in omega-6 fatty acids.
AB  - Chronic inflammation in gastrointestinal tract has been suggested as a risk
      factor for tumor formation. The effect of dietary supplementation of quercetin or
      beta-carotene on colon carcinogenesis and inflammatory response in rats fed with
      high-fat diet rich in omega-6 fatty acids was assessed. Animals were exposed to
      two weekly subcutaneous injections of AOM (azoxymethane) at a single dose of 15
      mg/kg body weight. A portion of rats from each group was sacrificed at 8 weeks
      after the last AOM treatment to determine ACF (aberrant crypt foci) formation.
      Colonic mucosa expression of iNOS (inducible nitric oxide) and COX-2
      (cyclooxygenase-2) protein, and blood PGE2 (prostaglandin E2) level were
      measured. The remaining groups of animals were sacrificed at 33 weeks after the
      last AOM treatment to examine colon tumor formation. Rats on high-fat diet
      developed more aberrant crypt foci (P<0.05) compared with those of rats on
      regular diet. In the same vein, but in contrast to the effect seen with regular
      diet, the high-fat diet induced a significant up-regulation of iNOS expression.
      There was no significant change in the extent of COX-2 expression or in the PGE2
      levels. Quercetin or beta-carotene supplementation reduced the number of ACF only
      in animals fed high-fat diet (p<0.05), however, no significant difference in
      tumor incidence was found. At week 33, the expression of iNOS was reduced by
      quercetin without a statistical significance, and COX-2 expression was slightly
      reduced in rats on beta-carotene supplementation. No change in PGE2 levels was
      observed. Whilst dietary antioxidants are considered as effective suppressors for
      precancerous lesion formation in colons exposed to high-risk diet, it is clear
      that elucidating the role of individual antioxidants in colon tumor formation
      coupled with an understanding of the molecular mechanisms involved would benefit
      colon cancer prevention strategies.

PMID- 17012771
TI  - Reversal of the TPA-induced inhibition of gap junctional intercellular
      communication by Chaga mushroom (Inonotus obliquus) extracts: effects on MAP
      kinases.
AB  - Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk
      medicine with indications for the treatment of cancers and digestive diseases.
      The anticarcinogenic effect of Chaga mushroom extract was investigated using a
      model system of gap junctional intercellular communication (GJIC) in WB-F344
      normal rat liver epithelial cells. The cells were pre-incubated with Chaga
      mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co
      treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13
      acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O
      tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with
      treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated
      ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts
      treated cells. There was no change in the JNK kinase protein level, suggesting
      that Chaga mushroom extracts could only block the activation of ERK1/2 and p38
      MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC
      through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication
      through gap junctional channels is a critical factor in the life and death
      balance of cells because GJIC has an important function in maintaining tissue
      homeostasis through the regulation of cell growth, differentiation, apoptosis and
      adaptive functions of differentiated cells. Thus Chaga mushroom may act as a
      natural anticancer product by preventing the inhibition of GJIC through the
      inactivation of ERK1/2 and p38 MAP kinase.

PMID- 17012772
TI  - Activity of the dietary antioxidant ergothioneine in a virus gene-based assay for
      inhibitors of HIV transcription.
AB  - The "Long Terminal Repeat" (LTR) of HIV-1 is the target of cellular transcription
      factors such as NF-kappaB, and serves as the promoter-enhancer for the viral
      genome when integrated in host DNA. Various LTR-reporter gene constructs have
      been used for in vitro studies of activators or inhibitors of HIV-1
      transcription, e.g., to show that antioxidants such as lipoic acid and selenium
      inhibit NF-kappaB-dependent HIV-1 LTR activation. One such construct is the
      pHIVlacZ plasmid, with the HIV-1 LTR driving expression of the lacZ gene
      (encoding beta-galactosidase, beta-gal). Typically, for inhibitor screening,
      cells transfected with pHIVlacZ are activated using tumor necrosis factor-alpha
      (TNF-alpha), and the colorimetric o-nitrophenol assay is used to assess changes
      in beta-gal activity. A variant of this assay was developed as described here, in
      which LTR activation was induced by pro-fs, a novel HIV-1 gene product encoded
      via a -1 frameshift from the protease gene. Cotransfection of cells with pHIVlacZ
      along with a pro-fs construct produced a significant increase in beta-gal
      activity over controls. L-ergothioneine dose dependently inhibited both TNF-alpha
      mediated and pro-fs-mediated increases in beta-gal activity, with an IC50 of
      about 6 mM. Thus antioxidant strategy involving ergothioneine derived from food
      plants might be of benefit in chronic immunodeficiency diseases.

PMID- 17012773
TI  - Exercise, oxidative stress and risk of cardiovascular disease in the elderly.
      Protective role of antioxidant functional foods.
AB  - Free radicals and oxidative stress are involved in the pathogenic mechanisms of
      cardiovascular disease (CVD), diabetes and cancer. Exercise is a useful strategy
      for preventing CVD but in elderly persons it can enhance oxidative stress, which
      is why some studies recommend antioxidant supplementation for exercising elderly
      subjects. This intervention study was performed on 320 elderly subjects following
      a Geriatric Revitalization Program (GEREPRO) to maintain physical health and
      reduce CVD risk. GEREPRO was based on regular exercise concurrent with a
      nutritional antioxidant treatment based on daily intake of a functional
      antioxidant food, Biofrutas. Sustained exercise (10 months, 3 sessions/week)
      significantly increased cardiorespiratory fitness and plasma HDL-cholesterol; it
      reduced some predictors of cardiovascular risk (arterial pressure, LDL
      cholesterol, total cholesterol/LDL-C, LDL-C/HDL-C), but significantly enhanced
      some biomarkers of oxidative stress. Concurrent antioxidant supplementation did
      not produce any ergogenic effects but, meaningfully, enhanced some positive
      effects of exercise on physical health and the CDV risk index, and it totally
      prevented the exercise-induced oxidative stress. Our results show that regular
      and moderate exercise improves cardiorespiratory function and reduces CVD risk in
      elderly people, while concurrent antioxidant supplementation modulates oxidative
      insult during exercise in the elderly and enhances the beneficial effects of
      exercise.

PMID- 17012774
TI  - The effects of reactive oxygen and nitrogen species during yeast replicative
      ageing.
AB  - Free radicals are considered the most important cause of cellular ageing. We have
      investigated ageing process in the yeast Saccharomyces cerevisiae. We have
      compared the wild type strain with the mutant cells with constitutively active
      Ras oncogen, which generates increased amounts of free radicals. Increased
      generation of oxygen-derived free radicals resulted in the Ras mutant cells
      accumulation of lipofuscin-like pigments during ageing. Ageing wild type cells
      did not accumulate lipofuscin-like pigments. This is quite unique feature among
      known biological models. It may be caused by increased concentration of alpha
      tocopherol (the most prominent lipophilic antioxidant) in the wild type cells. In
      contrast, the Ras mutant cells contained decreased levels of alpha tocopherol
      even in the young cells. This observation indicates that the increased free
      radical generation can overwhelm the endogenous antioxidant system. We have
      documented the involvement of nitrogen-derived free radicals in the yeast
      metabolism. Protein nitrotyrosine, a marker of the reactive nitrogen species, has
      significantly increased in the senescent Ras mutant cells. The wild type cells
      contained basic level of nitrotyrosine corresponding to its concentration found
      in non-activated mammalian macrophages.

PMID- 17012775
TI  - Bio-markers of lipid peroxidation in vivo: hydroxyoctadecadienoic acid and
      hydroxycholesterol.
AB  - The biological role of lipid peroxidation products has continued to receive a
      great deal of attention not only for the elucidation of pathological mechanisms
      but also for their practical application to clinical use as bio-markers. In the
      last fifty years, lipid peroxidation has been the subject of extensive studies
      from the viewpoints of mechanisms, dynamics, product analysis, involvement in
      diseases, inhibition, and biological signaling. Lipid hydroperoxides are formed
      as the major primary products, however they are substrates for various enzymes
      and they also undergo various secondary reactions. In this decade, F2
      isoprostanes from arachidonates and neuroprostanes from docosahexanoates have
      been proposed as bio-markers. Although these markers are formed by a free radical
      mediated oxidation, the yields from the parent lipids are minimal. Compared to
      these markers, hydroperoxy octadecadienoates (HPODE) from linoleates and
      oxysterols from cholesterols are yielded by much simpler mechanisms from more
      abundant parent lipids in vivo. Recently, the method in which both free and ester
      forms of hydroperoxides and ketones as well as hydroxides of linoleic acid and
      cholesterol are measured as total hydroxyoctadecadienoic acid (tHODE) and 7
      hydroxycholesterol (t7-OHCh), respectively, was proposed. The concentrations of
      tHODE and t7-OHCh determined by GC-MS analysis from physiological samples were
      much higher than that of 8-iso-prostagrandin F(2alpha). In addition to this
      advantage, hydrogen-donor activity of antioxidants in vivo could be determined by
      the isomeric-ratio of HODE (9- and 13-(Z,E)-HODE/9- and 13-(E,E)-HODE).

PMID- 17012776
TI  - The effect of plant cytokinin hormones on the production of ethylene, nitric
      oxide, and protein nitrotyrosine in ageing tobacco leaves.
AB  - Transgenic plants with genetically increased or decreased levels of cytokinins
      were used to investigate the effect of cytokinin level on the production of
      ethylene, a plant hormone with suggested role in senescence, and the production
      of nitric oxide, potentially important signalling and regulatory molecule. The
      production of these gases was followed during the course of leaf development and
      senescence. The production of ethylene and nitric oxide is under genetic control
      of genes other than those involved in regulation of senescence. The difference in
      basic ethylene and NO levels in different tobacco cultivars was higher than their
      changes in senescence. The results of this study did not indicate a direct link
      between ethylene production and cytokinin levels. However, there was a decreased
      production of NO in senescent leaves. Low cytokinins level was associated with
      increased NO production during leaf development. Protein nitrotyrosine proved to
      be a better indicator of the reactive nitrogen species than measuring of the NO
      production. Higher nitrotyrosine concentrations were found in insoluble proteins
      than in the soluble ones, pointing to membrane proteins as the primary targets of
      the reactive nitrogen species. In plants with elevated cytokinin levels the
      content of nitrated proteins decreased both in soluble and insoluble fractions.
      This finding indicates an antioxidative function of cytokinins against reactive
      nitrogen species.

PMID- 17012777
TI  - Mechanisms of adenosine-induced cytotoxicity and their clinical and physiological
      implications.
AB  - Extracellular ATP (ATPo) and adenosine are cytotoxic to several cancer cell
      lines, suggesting their potential use for anticancer therapy. Adenosine causes
      cytotoxicity, either when added exogenously or when generated from ATPo
      hydrolysis, via mechanisms which are not mutually exclusive and which involve,
      adenosine receptor activation, pyrimidine starvation and/or increases in
      intracellular S-adenosylhomocysteine: S-adenosylmethionine ratio. Given that
      adenosine also appears to protect against cytotoxicity via mechanisms including
      immunity against damage by oxygen free radicals, an understanding of the
      contribution of adenosine to ATPo-induced cytotoxicity is thus crucial, when
      considering any potential therapeutic use for these compounds. However, such an
      understanding has been largely hindered by the fact that many studies have not
      focused enough on the possibility that both ATPo and adenosine may mediate
      cytotoxicity in the same system. Such studies can benefit from use a range of
      ATPo concentrations when assessing the contribution of adenosine to ATPo-induced
      cytotoxicity. Whilst future molecular and pharmacological studies are needed to
      establish the nature of the cytotoxic adenosine receptor, it is possible that
      more than just one adenosine receptor type is involved and that the cytotoxic
      receptor(s) type is more likely to have a low affinity for adenosine. Activation
      of the adenosine receptor(s) would thus lead to cytotoxicity only at relatively
      high adenosine concentrations, while lower adenosine concentrations mediate non
      cytotoxic physiological effects.

PMID- 17012778
TI  - Bioavailability, antioxidant and immune-enhancing properties of zinc methionine.
AB  - Although a large number of transition metals and cations remarkably induce
      oxidative deterioration of biological macromolecules including lipids, proteins
      and DNA, the trace element zinc acts as a novel dietary supplement and an
      essential micronutrient, and serves a wide range of biological functions in human
      and animal health. Zinc promotes antioxidant and immune functions, stabilizes and
      maintains the structural integrity of biological membranes, and plays a pivotal
      role in skin and connective tissue metabolism and repair. Zinc is an integral
      constituent of a large number of enzymes including antioxidant enzymes, and
      hormones including glucagon, insulin, growth hormone, and sex hormones. High
      concentrations of zinc are found in the prostate gland and choroids of the eye.
      Zinc deficiency leads to biochemical abnormalities including the impairments of
      growth, dermal, gastrointestinal, neurologic and immunologic systems. Given its
      superior bioavailability, antioxidant and immune-enhancing properties, zinc
      methionine may serve as a novel dietary supplement to promote health benefits in
      humans and animals.

PMID- 17012779
TI  - Low molecular proanthocyanidin dietary biofactor Oligonol: Its modulation of
      oxidative stress, bioefficacy, neuroprotection, food application and
      chemoprevention potentials.
AB  - Interdisciplinary research endeavors are directed at understanding the molecular
      mechanisms of neurodegenerative and chronic diseases that affect human lifestyle.
      Hence the potential for developing medicinal herb-derived and food plant-derived
      prophylactic agents directed at neurological, metabolic, cardiovascular and
      psychiatric disorders abounds. Oligonol is a novel technology product emanating
      from the oligomerization of polyphenols, typically proanthocyanidin from a
      variety of fruits (grapes, apples, persimmons etc.) that has optimized
      bioavailability. It is an optimized phenolic product containing catechin-type
      monomers and oligomeric proanthocyanidins, the easily absorbed forms. Typically
      the constituents of Oligonol are 15-20% monomers, 8-12% dimers and 5-10% trimers.
      Supplementation of mice with Oligonol prior to the administration of ferric
      nitrilotriacetic complex (a Fenton chemistry model) significantly reduced the
      extent of lipid peroxidation in the kidney, brain and liver. Oligonol triggers
      apoptosis in the MCF-7 and MDA-MB-231 breast cancer cells through modulation of
      the pro-apoptotic Bcl-2 family of proteins and the MEK/ERK signaling pathway, an
      observation suggesting its important chemopreventive effects. The senescence
      accelerated strain of mice (SAM) are models of senescence acceleration and
      geriatric disorders which exhibit learning and memory deficits and enhanced
      production or defective control of oxidative stress leading.

PMID- 17012780
TI  - Structure of the heterotrimeric PCNA from Sulfolobus solfataricus.
AB  - PCNA is a ring-shaped protein that encircles DNA, providing a platform for the
      association of a wide variety of DNA-processing enzymes that utilize the PCNA
      sliding clamp to maintain proximity to their DNA substrates. PCNA is a homotrimer
      in eukaryotes, but a heterotrimer in crenarchaea such as Sulfolobus solfataricus.
      The three proteins are SsoPCNA1 (249 residues), SsoPCNA2 (245 residues) and
      SsoPCNA3 (259 residues). The heterotrimeric protein crystallizes in space group
      P2(1), with unit-cell parameters a = 44.8, b = 78.8, c = 125.6 A, beta = 100.5
      degrees. The crystal structure of this heterotrimeric PCNA molecule has been
      solved using molecular replacement. The resulting structure to 2.3 A sheds light
      on the differential stabilities of the interactions observed between the three
      subunits and the specificity of individual subunits for partner proteins.

PMID- 17012781
TI  - Structure of Staphylococcus aureus guanylate monophosphate kinase.
AB  - Nucleotide monophosphate kinases (NMPKs) are potential antimicrobial drug targets
      owing to their role in supplying DNA and RNA precursors. The present work reports
      the crystal structure of Staphylococcus aureus guanylate monophosphate kinase
      (SaGMK) at 1.9 A resolution. The structure shows that unlike most GMKs SaGMK is
      dimeric, confirming the role of the extended C-terminus in dimer formation as
      first observed for Escherichia coli GMK (EcGMK). One of the two SaGMK dimers
      within the crystal asymmetric unit has two monomers in different conformations:
      an open form with a bound sulfate ion (mimicking the beta-phosphate of ATP) and a
      closed form with bound GMP and sulfate ion. GMP-induced domain movements in SaGMK
      can thus be defined by comparison of these conformational states. Like other
      GMKs, the binding of GMP firstly triggers a partial closure of the enzyme,
      diminishing the distance between the GMP-binding and ATP-binding sites. In
      addition, the closed structure shows the presence of a potassium ion in contact
      with the guanine ring of GMP. The potassium ion appears to form an integral part
      of the GMP-binding site, as the Tyr36 side chain has significantly moved to form
      a metal ion-ligand coordination involving the lone pair of the side-chain O atom.
      The potassium-binding site might also be exploited in the design of novel
      inhibitors.

PMID- 17012782
TI  - Purification, crystallization and preliminary X-ray study of the fungal laccase
      from Cerrena maxima.
AB  - Laccases are members of the blue multi-copper oxidase family that oxidize
      substrate molecules by accepting electrons at a mononuclear copper centre and
      transferring them to a trinuclear centre. Dioxygen binds to the trinuclear centre
      and, following the transfer of four electrons, is reduced to two molecules of
      water. Crystals of the laccase from Cerrena maxima have been obtained and X-ray
      data were collected to 1.9 A resolution using synchrotron radiation. A
      preliminary analysis shows that the enzyme has the typical laccase structure and
      several carbohydrate sites have been identified. The carbohydrate chains appear
      to be involved in stabilization of the intermolecular contacts in the crystal
      structure, thus promoting the formation of well ordered crystals of the enzyme.
      Here, the results of an X-ray crystallographic study on the laccase from the
      fungus Cerrena maxima are reported. Crystals that diffract well to a resolution
      of at least 1.9 A (R factor = 18.953%; R(free) = 23.835; r.m.s.d. bond lengths,
      0.06 A; r.m.s.d. bond angles, 1.07 degrees) have been obtained despite the
      presence of glycan moieties. The overall spatial organization of C. maxima
      laccase and the structure of its copper-containing active centre have been
      determined by the molecular-replacement method using the laccase from Trametes
      versicolor (Piontek et al., 2002) as a structural template. In addition, four
      glycan-binding sites were identified and the 1.9 A X-ray data were used to
      determine the previously unknown primary structure of this protein. The identity
      (calculated from sequence alignment) between the C. maxima laccase and the T.
      versicolor laccase is about 87%. Tyr196 and Tyr372 show significant extra density
      at the ortho positions and this has been interpreted in terms of NO(2)
      substituents.

PMID- 17012783
TI  - Structure of armadillo ACBP: a new member of the acyl-CoA-binding protein family.
AB  - The X-ray structure of the tetragonal form of apo acyl-CoA-binding protein (ACBP)
      from the Harderian gland of the South American armadillo Chaetophractus villosus
      has been solved. ACBP is a carrier for activated long-chain fatty acids and has
      been associated with many aspects of lipid metabolism. Its secondary structure is
      highly similar to that of the corresponding form of bovine ACBP and exhibits the
      unique flattened alpha-helical bundle (up-down-down-up) motif reported for
      animal, yeast and insect ACBPs. Conformational differences are located in loops
      and turns, although these structural differences do not suffice to account for
      features that could be related to the unusual biochemistry and lipid metabolism
      of the Harderian gland.

PMID- 17012784
TI  - The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a
      monofunctional aspartokinase.
AB  - The activation of the beta-carboxyl group of aspartate catalyzed by aspartokinase
      is the commitment step to amino-acid biosynthesis in the aspartate pathway. The
      first structure of a microbial aspartokinase, that from Methanococcus jannaschii,
      has been determined in the presence of the amino-acid substrate L-aspartic acid
      and the nucleotide product MgADP. The enzyme assembles into a dimer of dimers,
      with the interfaces mediated by both the N- and C-terminal domains. The active
      site functional groups responsible for substrate binding and specificity have
      been identified and roles have been proposed for putative catalytic functional
      groups.

PMID- 17012785
TI  - Preparation, crystallization and preliminary X-ray analysis of protein YtlP from
      Bacillus subtilis.
AB  - Bacillus subtilis YtlP is a protein that is predicted to belong to the bacterial
      and archael 2'-5' RNA-ligase family. It contains 183 residues and two copies of
      the HXTX sequence motif conserved among proteins belonging to this family. In
      order to determine the structure of YtlP and to compare it with the paralogue
      YjcG and identified 2'-5' RNA ligases, the gene ytlP was amplified from B.
      subtilis genomic DNA and cloned into expression vector pET-21a. The soluble
      protein was produced in Escherichia coli, purified to homogeneity and crystals
      suitable for X-ray analysis were obtained. The crystal diffracted to 2.0 A and
      belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 34.16, b =
      48.54, c = 105.75 A.

PMID- 17012786
TI  - Crystallization and preliminary X-ray diffraction analysis of two
      extracytoplasmic solute receptors of the DctP family from Bordetella pertussis.
AB  - DctP6 and DctP7 are two Bordetella pertussis proteins which belong to the
      extracytoplasmic solute receptors (ESR) superfamily. ESRs are involved in the
      transport of substrates from the periplasm to the cytosol of Gram-negative
      bacteria. DctP6 and DctP7 have been crystallized and diffraction data were
      collected using a synchrotron-radiation source. DctP6 crystallized in space group
      P4(1)2(1)2, with unit-cell parameters a = 108.39, b = 108.39, c = 63.09 A, while
      selenomethionyl-derivatized DctP7 crystallized in space group P2(1)2(1)2(1), with
      unit-cell parameters a = 64.87, b = 149.83, c = 170.65 A. The three-dimensional
      structure of DctP7 will be determined by single-wavelength anomalous diffraction,
      while the DctP6 structure will be solved by molecular-replacement methods.

PMID- 17012787
TI  - Crystallization and preliminary X-ray analysis of Salmonella FliI, the ATPase
      component of the type III flagellar protein-export apparatus.
AB  - Most of the structural components making up the bacterial flagellum are
      translocated through the central channel of the growing flagellar structure by
      the type III flagellar protein-export apparatus in an ATPase-driven manner and
      are assembled at the growing end. FliI is the ATPase that drives flagellar
      protein export using the energy of ATP hydrolysis. FliI forms an oligomeric ring
      structure in order to attain maximum ATPase activity. In this study, FliI(Delta1
      18), an N-terminally truncated variant of FliI lacking the first 18 residues, was
      purified and crystallized. Crystals were obtained using the hanging-drop vapour
      diffusion technique with PEG 8000 as a precipitant. FliI(Delta1-18) crystals grew
      in the monoclinic space group P2(1), with unit-cell parameters a = 48, b = 73, c
      = 126 A, beta = 94 degrees, and diffracted to 2.4 A resolution. Anomalous
      difference Patterson maps of Os-derivative and Pt-derivative crystals showed
      significant peaks in their Harker sections, indicating that both derivatives are
      suitable for structure determination.

PMID- 17012788
TI  - Crystallization and preliminary crystallographic characterization of LmACR2, an
      arsenate/antimonate reductase from Leishmania major.
AB  - Arsenic is present in the biosphere owing either to the presence of pesticides
      and herbicides used in agricultural and industrial activities or to leaching from
      geological formations. The health effects of prolonged exposure to arsenic can be
      devastating and may lead to various forms of cancer. Antimony(V), which is
      chemically very similar to arsenic, is used instead in the treatment of
      leishmaniasis, an infection caused by the protozoan parasite Leishmania sp.; the
      reduction of pentavalent antimony contained in the drug Pentostam to the active
      trivalent form arises from the presence in the Leishmania genome of a gene,
      LmACR2, coding for the protein LmACR2 (14.5 kDa, 127 amino acids) that displays
      weak but significant sequence similarity to the catalytic domain of Cdc25
      phosphatase and to rhodanese enzymes. For structural characterization, LmACR2 was
      overexpressed, purified to homogeneity and crystallized in a trigonal space group
      (P321 or P3(1)21/P3(2)21). The protein crystallized in two distinct trigonal
      crystal forms, with unit-cell parameters a = b = 111.0, c = 86.1 A and a = b =
      111.0, c = 175.6 A, respectively. At a synchrotron beamline, the diffraction
      pattern extended to a resolution limit of 1.99 A.

PMID- 17012789
TI  - Cloning, purification, crystallization and preliminary X-ray crystallographic
      analysis of the biosynthetic N-acetylornithine aminotransferases from Salmonella
      typhimurium and Escherichia coli.
AB  - Acetylornithine aminotransferase (AcOAT) is a type I pyridoxal 5'-phosphate
      dependent enzyme catalyzing the conversion of N-acetylglutamic semialdehyde to N
      acetylornithine in the presence of alpha-ketoglutarate, a step involved in
      arginine metabolism. In Escherichia coli, the biosynthetic AcOAT also catalyzes
      the conversion of N-succinyl-L-2-amino-6-oxopimelate to N-succinyl-L,L
      diaminopimelate, one of the steps in lysine biosynthesis. It is closely related
      to ornithine aminotransferase. AcOAT was cloned from Salmonella typhimurium and
      E. coli, overexpressed in E. coli and purified using Ni-NTA affinity column
      chromatography. The enzymes crystallized in the presence of gabaculine. Crystals
      of E. coli AcOAT (eAcOAT) only diffracted X-rays to 3.5 A and were twinned. The
      crystals of S. typhimurium AcOAT (sAcOAT) diffracted to 1.9 A and had a dimer in
      the asymmetric unit. The structure of sAcOAT was solved by the molecular
      replacement method.

PMID- 17012790
TI  - Preparation, crystallization and preliminary X-ray analysis of the methionine
      synthase (MetE) from Streptococcus mutans.
AB  - The Streptococcus mutans metE gene encodes methionine synthase (MetE), which
      catalyzes the direct transfer of a methyl group from methyltetrahydrofolate to
      homocysteine in the last step of methionine synthesis. metE was cloned into
      pET28a and the gene product was expressed at high levels in the Escherichia coli
      strain BL21 (DE3). MetE was purified to homogeneity using Ni(2+)-chelating
      chromatography followed by size-exclusion chromatography. Crystals of the protein
      were obtained by the hanging-drop vapour-diffusion method and diffracted to 2.2 A
      resolution. The crystal belongs to space group P2(1), with unit-cell parameters a
      = 52.85, b = 99.48, c = 77.88 A, beta = 94.55 degrees .

PMID- 17012791
TI  - Expression, purification, crystallization and preliminary X-ray analysis of two
      arginine-biosynthetic enzymes from Mycobacterium tuberculosis.
AB  - The gene products of two open reading frames from Mycobacterium tuberculosis
      (Mtb) have been crystallized using the sitting-drop vapour-diffusion method.
      Rv1652 encodes a putative N-acetyl-gamma-glutamyl-phosphate reductase (MtbAGPR),
      while the Rv1656 gene product is annotated as ornithine carbamoyltransferase
      (MtbOTC). Both MtbAGPR and MtbOTC were expressed in Escherichia coli, purified to
      homogeneity and crystallized. Native data for each crystal were collected to
      resolutions of 2.15 and 2.80 A, respectively. Preliminary X-ray data are
      presented for both enzymes.

PMID- 17012792
TI  - The purification, crystallization and preliminary structural characterization of
      FAD-dependent monooxygenase PhzS, a phenazine-modifying enzyme from Pseudomonas
      aeruginosa.
AB  - The blue chloroform-soluble bacterial metabolite pyocyanin (1-hydroxy-5-methyl
      phenazine) contributes to the survival and virulence of Pseudomonas aeruginosa,
      an important Gram-negative opportunistic pathogen of humans and animals. Little
      is known about the two enzymes, designated PhzM and PhzS, that function in the
      synthesis of pyocyanin from phenazine-1-carboxylic acid. In this study, the FAD
      dependent monooxygenase PhzS was purified and crystallized from lithium
      sulfate/ammonium sulfate/sodium citrate pH 5.5. Native crystals belong to space
      group C2, with unit-cell parameters a = 144.2, b = 96.2, c = 71.7 A, alpha =
      gamma = 90, beta = 110.5 degrees. They contain two monomers of PhzS in the
      asymmetric unit and diffract to a resolution of 2.4 A. Seleno-L-methionine
      labelled PhzS also crystallizes in space group C2, but the unit-cell parameters
      change to a = 70.6, b = 76.2, c = 80.2 A, alpha = gamma = 90, beta = 110.5
      degrees and the diffraction limit is 2.7 A.

PMID- 17012793
TI  - Crystallization and preliminary X-ray diffraction studies of a hyperthermophilic
      Rieske protein variant (SDX-triple) with an engineered rubredoxin-like
      mononuclear iron site.
AB  - In place of the Rieske [2Fe-2S] cluster, an archetypal mononuclear iron site has
      rationally been designed into a hyperthermophilic archaeal Rieske [2Fe-2S]
      protein (sulredoxin) from Sulfolobus tokodaii by three residue replacements with
      reference to the Pyrococcus furiosus rubredoxin sequence. The resulting
      sulredoxin variant, SDX-triple (H44I/A45C/H64C), has been purified and
      crystallized by the hanging-drop vapour-diffusion method using 65%(v/v) 2-methyl
      2,4-pentanediol, 0.025 M citric acid and 0.075 M sodium acetate trihydrate pH
      4.3. The crystals diffract to 1.63 A resolution and belong to the triclinic space
      group P1, with unit-cell parameters a = 43.56, b = 76.54, c = 80.28 A, alpha =
      88.12, beta = 78.82, gamma = 73.46 degrees. The asymmetric unit contains eight
      protein molecules.

PMID- 17012794
TI  - Crystallization and preliminary crystallographic study of carnosinase CN2 from
      mice.
AB  - Mammalian tissues contain several histidine-containing dipeptides, of which L
      carnosine is the best characterized and is found in various tissues including the
      brain and skeletal muscles. However, the mechanism for its biosynthesis and
      degradation have not yet been fully elucidated. Crystallographic study of
      carnosinase CN2 from mouse has been undertaken in order to understand its
      enzymatic mechanism from a structural viewpoint. CN2 was crystallized by the
      hanging-drop vapour-diffusion technique using PEG 3350 as a precipitant. Crystals
      were obtained in complex with either Mn(2+) or Zn(2+). Both crystals of CN2
      belong to the monoclinic space group P2(1) and have almost identical unit-cell
      parameters (a = 54.41, b = 199.77, c = 55.49 A, beta = 118.52 degrees for the
      Zn(2+) complex crystals). Diffraction data were collected to 1.7 and 2.3 A for
      Zn(2+) and Mn(2+) complex crystals, respectively, using synchrotron radiation.
      Structure determination is ongoing using the multiple-wavelength anomalous
      diffraction (MAD) method.

PMID- 17012795
TI  - Cloning, crystallization and preliminary X-ray study of XC1258, a CN-hydrolase
      superfamily protein from Xanthomonas campestris.
AB  - CN-hydrolase superfamily proteins are involved in a wide variety of non-peptide
      carbon-nitrogen hydrolysis reactions, producing some important natural products
      such as auxin, biotin, precursors of antibiotics etc. These reactions all involve
      attack on a cyano or carbonyl carbon by a conserved novel catalytic triad Glu-Lys
      Cys through a thiol acylenzyme intermediate. However, classification into the CN
      hydrolase superfamily based on sequence similarity alone is not straightforward
      and further structural data are necessary to improve this categorization. Here,
      the cloning, expression, crystallization and preliminary X-ray analysis of
      XC1258, a CN-hydrolase superfamily protein from the plant pathogen Xanthomonas
      campestris (Xcc), are reported. The SeMet-substituted XC1258 crystals diffracted
      to a resolution of 1.73 A. They are orthorhombic and belong to space group
      P2(1)2(1)2, with unit-cell parameters a = 143.8, b = 154.63, c = 51.3 A,
      respectively.

PMID- 17012796
TI  - Crystallization and preliminary X-ray analysis of CTP:phosphoethanolamine
      cytidylyltransferase (ECT) from Saccharomyces cerevisiae.
AB  - CTP:phosphoethanolamine cytidylyltransferase (ECT) is the enzyme that catalyzes
      the conversion of phosphoethanolamine to CDP-ethanolamine in the
      phosphatidylethanolamine-biosynthetic pathway (Kennedy pathway). ECT from
      Saccharomyces cerevisiae was crystallized by the sitting-drop vapour-diffusion
      method using PEG 4000 as precipitant. The crystals diffracted X-rays from a
      synchrotron-radiation source to 1.88 A resolution. The space group was assigned
      as primitive tetragonal, P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a =
      b = 66.3, c = 150.8 A. The crystals contain one ECT molecule in the asymmetric
      unit (V(M) = 2.2 A(3) Da(-1)), with a solvent content of 43%.

PMID- 17012797
TI  - Cloning, purification and preliminary crystallographic analysis of a putative
      pyridoxal kinase from Bacillus subtilis.
AB  - Pyridoxal kinases (PdxK) are able to catalyse the phosphorylation of three
      vitamin B(6) precursors, pyridoxal, pyridoxine and pyridoxamine, to their 5'
      phosphates and play an important role in the vitamin B(6) salvage pathway.
      Recently, the thiD gene of Bacillus subtilis was found to encode an enzyme which
      has the activity expected of a pyridoxal kinase despite its previous assignment
      as an HMPP kinase owing to higher sequence similarity. As such, this enzyme would
      appear to represent a new class of ;HMPP kinase-like' pyridoxal kinases. B.
      subtilis thiD has been cloned and the protein has been overexpressed in
      Escherichia coli, purified and subsequently crystallized in a binary complex with
      ADP and Mg(2+). X-ray diffraction data have been collected from crystals to 2.8 A
      resolution at 100 K. The crystals belong to a primitive tetragonal system, point
      group 422, and analysis of the systematic absences suggest that they belong to
      one of the enantiomorphic pair of space groups P4(1)2(1)2 or P4(3)2(1)2.
      Consideration of the space-group symmetry and unit-cell parameters (a = b =
      102.9, c = 252.6 A, alpha = beta = gamma = 90 degrees ) suggest that the crystals
      contain between three and six molecules in the asymmetric unit. A full structure
      determination is under way to provide insights into aspects of the enzyme
      mechanism and substrate specificity.

PMID- 17012798
TI  - Expression, purification and crystallization of 2-oxo-hept-4-ene-1,7-dioate
      hydratase (HpcG) from Escherichia coli C.
AB  - The gene encoding 2-oxo-hept-3-ene-1,7-dioic acid (OHED) hydratase (HpcG) was
      cloned into the high-expression plasmid pET26b and overexpressed in Escherichia
      coli BL21(DE3). The enzyme was purified in three steps to greater than 95% purity
      prior to crystallization. Crystals were obtained by the hanging-drop vapour
      diffusion method at 277 K in a number of screening conditions. Crystals measuring
      up to 1.5 mm in their longest dimension were grown from solutions containing
      polyethylene glycol 20 000. The crystals belonged to space group P4(1)2(1)2 or
      P4(3)2(1)2, with unit-cell parameters a = 136, b = 136, c = 192 A. A complete
      data set was collected to 2.1 A from a single cryocooled crystal at 100 K using
      synchrotron radiation.

PMID- 17012799
TI  - Crystallization and preliminary X-ray analysis of bacteriophage T4 UvsY
      recombination mediator protein.
AB  - Bacteriophage T4 UvsY protein is considered to be the prototype of recombination
      mediator proteins, a class of proteins which assist in the loading of
      recombinases onto DNA. Wild-type and Se-substituted UvsY protein have been
      expressed and purified and crystallized by hanging-drop vapor diffusion. The
      crystals diffract to 2.4 A using in-house facilities and to 2.2 A at NSLS,
      Brookhaven National Laboratory. The crystals belong to space group P422, P4(2)22,
      P42(1)2 or P4(2)2(1)2, the ambiguity arising from pseudo-centering, with unit
      cell parameters a = b = 76.93, c = 269.8 A. Previous biophysical characterization
      of UvsY indicates that it exists primarily as a hexamer in solution. Along with
      the absence of a crystallographic threefold, this suggests that the asymmetric
      unit of these crystals is likely to contain either three monomers, giving a
      solvent content of 71%, or six monomers, giving a solvent content of 41%.

PMID- 17012800
TI  - Crystallization and preliminary X-ray analysis of Atg3.
AB  - Atg3 is an E2-like enzyme that catalyzes the conjugation reaction between Atg8
      and phosphatidylethanolamine (PE). The Atg8-PE conjugate is essential for
      autophagy, the bulk degradation process of cytoplasmic components by the
      vacuolar/lysosomal system. Crystals of Saccharomyces cerevisiae Atg3 have been
      obtained by the sitting-drop vapour-diffusion method using ammonium sulfate and
      lithium sulfate as precipitants. A native data set was collected from a single
      crystal to 2.5 A resolution. The crystals belong to space group P4(1) or P4(3),
      with unit-cell parameters a = 59.33, c = 115.22 A, and are expected to contain
      one protein molecule per asymmetric unit.

PMID- 17012801
TI  - Crystallization and preliminary crystallographic analysis of p40phox, a
      regulatory subunit of NADPH oxidase.
AB  - p40(phox) is a cytosolic component of the phagocyte NADPH oxidase, which is
      responsible for production of the superoxide that kills invasive microorganisms.
      Full-length p40(phox) was expressed in Escherichia coli, purified and
      crystallized by the sitting-drop vapour-diffusion method at 293 K using
      polyethylene glycol 20,000 as a precipitant. Diffraction data were collected to
      3.0 A resolution at 100 K using synchrotron radiation. The crystal belongs to
      space group C222(1), with unit-cell parameters a = 146.27, b = 189.81, c = 79.88
      A. This crystal was estimated to contain two or three protein molecules per
      asymmetric unit from the acceptable range of volume-to-weight ratio values.

PMID- 17012802
TI  - Expression, purification and crystallization of the Atg5-Atg16 complex essential
      for autophagy.
AB  - Atg5 is a novel 34 kDa protein that is covalently modified by Atg12, a ubiquitin
      like modifier, and forms a complex with Atg16. The Atg12-Atg5-Atg16 complex
      localizes to autophagosome precursors and plays an essential role in
      autophagosome formation. Saccharomyces cerevisiae Atg5 in complex with the N
      terminal regions of Atg16 was expressed, purified and crystallized in four
      crystal forms. Forms I, II and III belong to space group P2(1), with unit-cell
      parameters a = 66.3, b = 104.4, c = 112.1 A, beta = 92.1 degrees (form I), a =
      79.5, b = 101.4, c = 95.1 A, beta = 98.6 degrees (form II) or a = 56.9, b =
      101.2, c = 66.5 A, beta = 100.6 degrees (form III). Form IV belongs to space
      group P4(2)2(1)2, with unit-cell parameters a = 73.3, c = 148.1 A. Diffraction
      data were collected from all crystal forms and high-resolution data to beyond 2.0
      A resolution were obtained from a form IV crystal.

PMID- 17012803
TI  - Crystallization and preliminary X-ray diffraction analysis of Salmonella typhi
      PilS.
AB  - The structure determination of PilS, a type IV pilin, by X-ray crystallography is
      reported. The recombinant protein from Salmonella typhi was overexpressed,
      purified and crystallized. The crystals belong to space group P2(1)2(1)2, with
      unit-cell parameters a = 77.88, b = 114.53, c = 31.75 A. The selenomethionine
      derivative of the PilS protein was overexpressed, purified and crystallized in
      the same space group. Data sets have been collected to 2.1 A resolution from the
      selenomethionine-derivative crystal using synchrotron radiation for
      multiwavelength anomalous dispersion (MAD) phasing.

PMID- 17012804
TI  - Crystallization and preliminary crystallographic analysis of the transcriptional
      regulator RfaH from Escherichia coli and its complex with ops DNA.
AB  - The bacterial transcriptional factor and virulence regulator RfaH binds to
      rapidly moving transcription elongation complexes through specific interactions
      with the exposed segment of the non-template DNA strand. To elucidate this
      unusual mechanism of recruitment, determination of the three-dimensional
      structure of RfaH and its complex with DNA was initiated. To this end, the
      Escherichia coli rfaH gene was cloned and expressed. The purified protein was
      crystallized by the sitting-drop vapor-diffusion technique. The space group was
      P6(1)22 or P6(5)22, with unit-cell parameters a = b = 45.46, c = 599.93 A. A
      complex of RfaH and a nine-nucleotide oligodeoxyribonucleotide was crystallized
      by the same technique, but under different crystallization conditions, yielding
      crystals that belonged to space group P1 (unit-cell parameters a = 36.79, b =
      44.01, c = 62.37 A, alpha = 80.62, beta = 75.37, gamma = 75.41 degrees ).
      Complete diffraction data sets were collected for RfaH and its complex with DNA
      at 2.4 and 1.6 A resolution, respectively. Crystals of selenomethionine-labeled
      proteins in both crystal forms were obtained by cross-microseeding using the
      native microcrystals. The structure determination of RfaH and its complex with
      DNA is in progress.

PMID- 17012805
TI  - Crystallization and preliminary X-ray crystallographic analysis of the catalytic
      domain of pyrrolysyl-tRNA synthetase from the methanogenic archaeon
      Methanosarcina mazei.
AB  - Pyrrolysyl-tRNA synthetase (PylRS) from Methanosarcina mazei was overexpressed in
      an N-terminally truncated form PylRS(c270) in Escherichia coli, purified to
      homogeneity and crystallized by the hanging-drop vapour-diffusion method using
      polyethylene glycol as a precipitant. The native PylRS(c270) crystals in complex
      with an ATP analogue belonged to space group P6(4), with unit-cell parameters a =
      b = 104.88, c = 70.43 A, alpha = beta = 90, gamma = 120 degrees , and diffracted
      to 1.9 A resolution. The asymmetric unit contains one molecule of PylRS(c270).
      Selenomethionine-substituted protein crystals were prepared in order to solve the
      structure by the MAD phasing method.

PMID- 17012806
TI  - Expression, purification and crystallization of L-methionine gamma-lyase 2 from
      Entamoeba histolytica.
AB  - L-Methionine gamma-lyase (MGL) is considered to be an attractive target for
      rational drug development because the enzyme is absent in mammalian hosts. To
      enable structure-based design of drugs targeting MGL, one of the two MGL
      isoenzymes (EhMGL2) was crystallized in the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 88.89, b = 102.68, c = 169.87 A. The
      crystal diffracted to a resolution of 2.0 A. The presence of a tetramer in the
      asymmetric unit (4 x 43.1 kDa) gives a Matthews coefficient of 2.2 A(3) Da(-1).
      The structure was solved by the molecular-replacement method and structure
      refinement is now in progress.

PMID- 17012807
TI  - Crystallization and preliminary X-ray crystallographic studies of pig heart
      carbonyl reductase.
AB  - Pig heart carbonyl reductase (PHCR), which belongs to the short-chain
      dehydrogenase/reductase (SDR) family, has been crystallized by the hanging-drop
      vapour-diffusion method. Two crystal forms (I and II) have been obtained in the
      presence of NADPH. Form I crystals belong to the tetragonal space group P4(2),
      with unit-cell parameters a = b = 109.61, c = 94.31 A, and diffract to 1.5 A
      resolution. Form II crystals belong to the tetragonal space group P4(1)2(1)2,
      with unit-cell parameters a = b = 120.10, c = 147.00 A, and diffract to 2.2 A
      resolution. Both crystal forms are suitable for X-ray structure analysis at high
      resolution.

PMID- 17012808
TI  - A serendipitous discovery that in situ proteolysis is essential for the
      crystallization of yeast CPSF-100 (Ydh1p).
AB  - The cleavage and polyadenylation specificity factor (CPSF) complex is required
      for the cleavage and polyadenylation of the 3'-end of messenger RNA precursors in
      eukaryotes. During structural studies of the 100 kDa subunit (CPSF-100, Ydh1p) of
      the yeast CPSF complex, it was serendipitously discovered that a solution that is
      infected by a fungus (subsequently identified as Penicillium) is crucial for the
      crystallization of this protein. Further analyses suggest that the protein has
      undergone partial proteolysis during crystallization, resulting in the deletion
      of an internal segment of about 200 highly charged and hydrophilic residues, very
      likely catalyzed by a protease secreted by the fungus. With the removal of this
      segment, yeast CPSF-100 (Ydh1p) has greatly reduced solubility and can be
      crystallized in the presence of a minute amount of precipitant.

PMID- 17012809
TI  - The cloning, crystallization and preliminary X-ray analysis of XC2113, a YaeQ
      protein from Xanthomonas campestris.
AB  - Xanthomonas campestris is a Gram-negative bacterium that is phytopathogenic to
      cruciferous plants and causes worldwide agricultural loss. It is therefore
      important to identify potential pathogenic factors involved in this plant
      disease. Here, the cloning, expression, crystallization and preliminary X-ray
      analysis of XC2113, a YaeQ protein possibly involved in the production of
      virulence factors in Xanthomonas campestris pathovar campestris, are reported.
      The XC2113 crystals diffracted well to a resolution of at least 1.28 A. They are
      orthorhombic and belong to space group P2(1)2(1)2(1), with unit-cell parameters a
      = 32.86, b = 62.69, c = 79.96 A.

PMID- 17012810
TI  - Crystallization and preliminary X-ray diffraction analysis of Leishmania major
      dihydroorotate dehydrogenase.
AB  - Dihydroorotate dehydrogenases (DHODHs) are flavin-containing enzymes that
      catalyze the oxidation of L-dihydroorotate to orotate, the fourth step in the de
      novo pyrimidine nucleotide synthesis pathway. In this study, DHODH from
      Leishmania major has been crystallized by the vapour-diffusion technique using
      lithium sulfate as the precipitating agent. The crystals belong to space group
      P6(1), with unit-cell parameters a = 143.7, c = 69.8 A. X-ray diffraction data
      were collected to 2.0 A resolution using an in-house rotating-anode generator.
      Analysis of the solvent content and the self-rotation function indicate the
      presence of two molecules in the asymmetric unit. The structure has been solved
      by the molecular-replacement technique.

PMID- 17012811
TI  - [Prevention of osteoporosis by foods and dietary supplements. Prevention of
      osteoporosis by milk and dairy products].
AB  - Milk and dairy products, which are rich in calcium and high in calcium
      absorption, are useful foods for prevention of osteoporosis. Milk and dairy
      products are not only good sources for protein, lipids, sodium, potassium,
      phosphate, zinc, and vitamins A and B(2), and also contain functional compounds
      including milk basic protein (MBP), casein phosphopeptide (CPP), and lactoferrin,
      which are beneficial for bone health. Since some reports show that the preventive
      effect of dairy products consumption for bone fracture is not strong enough, but
      the effects may be more efficient in Japanese, whose calcium consumption is low.
      Consumption of milk and dairy products in Japanese is still low, and it is
      important to keep our mind to increase its consumption for bone health.

PMID- 17012812
TI  - [Prevention of osteoporosis by foods and dietary supplements. Bioavailability of
      milk micellar calcium phosphate].
AB  - Micellar calcium phosphate (MCP), which is a main form in milk, cross-links
      caseins through their phosphate groups. MCP was separated as the complex with
      casein phosphopeptide (CPP). Whey calcium, which is separated in a different form
      from that in bovine milk and used as a calcium ingredient in recent food
      industry, has superior calcium bioavailability to other calcium ingredients.
      Growing female rats were fed either MCP-CPP complex or whey calcium as the sole
      source of calcium for 6 weeks, and the calcium bioavailability was estimated from
      apparent calcium absorption rate and the bone strength of the femur. The calcium
      bioavailability of the MCP-CPP complex was significantly higher than that of whey
      calcium. The higher calcium bioavailability of MCP-CPP complex is due to in part
      to its solubility in the small intestine.

PMID- 17012813
TI  - [Prevention of osteoporosis by foods and dietary supplements. Bone reinforcement
      factor in milk: milk basic protein (MBP)].
AB  - Milk has been drunk widely for long time, because it contains superior nutritive
      value. In particular, milk is the supplying source of good calcium of
      bioavailability, in comparison with other foods. In addition, whey protein is a
      by-product of cheese and casein production, and we have showed that this whey
      protein plays a functional role for bone remodeling (bone formation and bone
      resorption). And, it became clear by an examination of in vitro that there were
      the active substances that promote bone formation and suppress bone resorption in
      the basic protein fraction (milk basic protein: MBP). Furthermore, it was shown
      that whey protein and MBP enhanced bone strength of femur in ovariectomized rats.
      In addition, some human studies clearly showed that MBP improved the balance of
      bone metabolism and increased bone density. As for MBP, MBP, which contributes to
      bone health, is expected as a new food material extracted from milk.

PMID- 17012814
TI  - [Prevention of osteoporosis by foods and dietary supplements. Milk basic protein
      (MBP) increases bone mineral density in young adult women and perimenopausal
      women].
AB  - Milk has beneficial effects on bone health than other food sources. Recent in
      vitro and in vivo studies have shown that milk whey protein, especially its basic
      protein fraction (milk basic protein: MBP), contains components capable of
      promoting bone formation and inhibiting bone resorption. We tried to examine the
      effect of MBP on bone mineral density (BMD) and markers of bone metabolism in
      healthy young adult women and perimenopausal women. In the healthy young women
      study, we found that MBP increased BMD, by promoting bone formation and
      inhibiting bone resorption. In the healthy perimenopausal women study, we also
      found that MBP increased BMD, primarily by inhibiting bone resorption, while
      maintaining bone formation. Thus, bone remodeling balances become positive that
      leads to maintenance or increase of bone formation. MBP supplementation could be
      effective for bone health in a wide range of generation especially those who hate
      to drink milk.

PMID- 17012815
TI  - [Prevention of osteoporosis by foods and dietary supplements. Milk basic protein
      (MBP) induces alveolar bone formation in rat experimental periodontitis].
AB  - Periodontitis is a chronic inflammatory disease caused by infection of
      periodontopathic bacteriae, which induced alveolar bone resorpotion. Milk basic
      protein (MBP) has been reported to be useful as a supplement because of
      increasing bone formation in animal and human studies. We examined the effect of
      MBP for alveolar bone formation in rat experimental periodontitis. After alveolar
      bone resorption was induced by ligature technique, the diets containing low and
      high dose of MBP were given to rats for 90 days. Micro-focus computed tomography
      and histological observation revealed a recovery of alveolar bone in high-dose
      MBP group compared to the control group. Osteoid thickness of alveolar bone crest
      significantly increased in low and high-dose MBP groups. These findings indicate
      that MBP may be effective for the recovery of alveolar bone resorption in
      periodontitis.

PMID- 17012816
TI  - [Prevention of osteoporosis by foods and dietary supplements. Vitamin D and bone
      metabolism].
AB  - Vitamin D is an essential nutrient for maintenance of calcium homeostasis. In
      case of vitamin D deficiency, low vitamin D production rate in skin, insufficient
      metabolic activation of vitamin D, reduction of bone mass, and osteoporosis would
      be induced. In the last year, "Dietary Reference Intakes for Japanese, 2005" was
      published by Ministry of Health, Labour, and Welfare, Japan. This reference was
      based on the concept of the dietary reference intake (DRIs). The parameter for
      the assessment of vitamin D nutrition status was defined on the basis of the
      plasma levels of 25-hydroxyvitamin D, and established as "adequate intake" in the
      reference. The dietary vitamin D intake for prevention of osteoporosis will be
      more important according to the progress of examination of dietary vitamin D
      intake in Japanese.

PMID- 17012817
TI  - [Prevention of osteoporosis by foods and dietary supplements. Vitamin K and bone
      metabolism].
AB  - Many reports have indicated the significant correlation between low vitamin K
      intakes and the increased prevalence of osteoporotic fractures. The role of
      vitamin K in bone metabolism is assumed to be mediated by carboxylation of
      vitamin-K-dependent proteins. In addition, recent researches suggest the novel
      action of vitamin K(2) via nuclear receptors. The role of vitamin K in the
      prevention as well as the treatment of osteoporosis should be more emphasized.

PMID- 17012818
TI  - [Prevention of osteoporosis by foods and dietary supplements. Magnesium and bone
      metabolism].
AB  - About half the total magnesium (Mg) of the body is existed in bone. Bone is one
      of the main Mg pools in the body. Epidemiologic studies have demonstrated a
      positive correlation between Mg intake and bone mineral density. It is also
      reported that Mg deficiency induced a decrease in osteoblasts number, an increase
      in osteoclasts number and a decrease in bone strength in rats. In contrast,
      dietary Mg supplementation improved bone formation, bone resorption and bone
      strength in ovariectomized rats. Mg deficiency is known as a risk factor for
      osteoporosis, since Mg is essential mineral for normal bone growth. However, the
      detail of effects of Mg on bone metabolism remains unclear. Further studies
      should be developed to clarify the details.

PMID- 17012819
TI  - [Prevention of osteoporosis by foods and dietary supplements. Soybean isoflavone
      and bone metabolism].
AB  - Soybean isoflavones show structural similarity to estradiol and therefore are
      known as phytoestrogen. Recently, isoflavones have received a great deal of
      attention for their preventive roles against hormone dependent diseases including
      postmenopausal osteoporosis, hyperlipidemia and cancer. Particularly, a number of
      studies have reported that soybean isoflavones inhibited bone loss in both female
      and male osteoporotic animal models as well as in postmenopausal women. On the
      other hand, since a kind of tablet with concentrated isoflavones has been
      recently applied for foods for specified health use (FOSHU), which are functional
      foods permitted to label a health claim by the Ministry of Health, Labor and
      Welfare in Japan, Food Safety Commission submitted a report the upper limit of
      daily isoflavone aglycon intake from FOSHU as well as from soybean products. This
      report demonstrates the effects of isoflavones on bone metabolism and safety.

PMID- 17012820
TI  - [Prevention of osteoporosis by foods and dietary supplements. Hesperidin and bone
      metabolism].
AB  - Among the naturally occurring citrus flavonoids, hesiperidin, a flavanon
      glycocide, may be associated with potential benefits in the prevention of
      diseases, such as decreasing capillary permeability, anti inflammatory,
      antimicrobial and anti carcinogenic effects. Hesperidin also regulates hepatic
      cholesterol synthesis by inhibiting the activity of 3-hydroxy-3-methlyglutaryl
      coenzyme A (HMG-CoA) reductase. Recently, Mundy et al. reported that statins,
      cholesterol lowering agents, induce bone formation and inhibit bone resorption
      both in vitro and in vivo. Thus, considerable attention has focused on the
      relationship between the inhibitory activity on HMG-CoA reductase and bone
      action. We examined the effects of hesperidin on bone metabolism in
      ovariectomized mice, orhiectomized mice and magnesium deficient rats, animal
      models of osteoporosis. Hesperidin inhibited bone loss the animals with lowering
      serum and hepatic cholesterol. These results suggest hesperidin may act on bone
      by the same mechanism as that of statins. Further studies are needed to define
      hesperidin's mechanisms of action on bone.

PMID- 17012821
TI  - [Prevention of osteoporosis by foods and dietary supplements. The effect of
      fructooligosaccharides (FOS) on the calcium absorption and bone].
AB  - Fructooligosaccharides (FOS) are well known as prebiotics which improve
      intestinal microflaura. FOS also have increasing effect on the intestinal
      absorption of calcium (Ca), magnesium (Mg) and iron. These effects were inspected
      by many animal experiments and then by human studies. Especially, FOS clearly
      prevent the decrease of bone mineral density by gastrectomy in rats. In this
      report, we mainly explain the preventive effect of FOS on the bone of
      gastrectomized rats and introduce relationship between another food ingredient or
      exercise.

PMID- 17012822
TI  - [Prevention of osteoporosis by foods and dietary supplements. What are foods for
      specified health uses (FOSHU)?].
AB  - Foods for specified health uses (FOSHU) are foods to which a "functional"
      ingredient has been added for a specific healthful effect. Approved by the
      Ministry of Health, Labour and Welfare, these foods have been designed to
      maintain and promote good health. Main guidelines for application, evaluation and
      labeling for FOSHU is following. (1)FOSHU should be evaluation in its
      effectiveness and safety scientifically by the Council of Pharmaceutical affairs
      and Food Hygiene and Food Safety Commission. (2)Functional labeling of FOSHU
      should be on science basis, but should not imply prevention, treatment and
      diagnosis of human disease.

PMID- 17012823
TI  - [Prevention of osteoporosis by foods and dietary supplements. "Daizuga-cha",
      Kuromame-cha"].
AB  - Soy isoflavones have been suggested to alleviate osteoporosis by inhibiting bone
      resorption. Our finding indicates that consumption of the drink "Daizuga-cha",
      which contains isoflavones reduced urinary excretion of pyridinoline (p = 0.09)
      and deoxypyridinoline (p<0.05) in Japanese women (average age: 55.6 years).
      "Daizuga-cha" is the first drink approved by the Japanese ministry of health,
      labor and welfare as a "food for specified health uses (FOSHU)" for bone health.
      Recent clinical data suggest that approximately 30-70 mg/day of isoflavones (as
      aglycone) are required by younger postmenopausal women in order to derive
      skeletal benefits. However, isoflavone intake among such women in Japan is often
      lower than this level. Consumption of soy foods and soy isoflavone FOSHU
      ("Daizuga-cha", "Kuromame-cha", "Kuromame-soymilk drink", and "Kuromame-cha
      Gold") has the potential to reduce the risk of postmenopausal osteoporosis.

PMID- 17012824
TI  - [Prevention of osteoporosis by foods and dietary supplements. "Mainichi Hone Kea
      MBP": A foods for specified health uses (FOSHU) product containing MBP that has
      an effect to increase bone density].
AB  - "Mainichi Hone Kea MBP" is a foods for specified health uses (FOSHU) product. It
      has been approved to write the next claim, "This product is suitable for those
      who care about bone health, because it contains MBP that has an effect to
      increase bone density", on this product. MBP is a complex of protein with a basic
      isoelectric point in milk protein. It has been shown that MBP promotes bone
      formation, suppresses bone resorption, increases bone mineral density, and
      increases bone strength in in vitro and in vivo studies. And, we also examined
      the effect of MBP in healthy adult women from twenties to fifties. A beverage
      containing MBP or a placebo beverage without MBP was given to volunteers for six
      months. The percentage increase of radial bone density was significantly higher
      in the MBP group than in the placebo group. This result has confirmed that MBP
      contributes to increased bone density in humans. To sum up, we believe that
      MAINICHI HONE KEA MBP, which contains MBP that has an effect to increase bone
      density, contributes to bone health.

PMID- 17012825
TI  - [Prevention of osteoporosis by foods and dietary supplements. Chocolate malt
      drink MILO: nutrition in children and calcium absorption].
AB  - Calcium is not sufficiently consumed by Japanese at any age groups. Childhood is
      an important period, when they should earn bone minerals to reach higher peak
      bone mass for reducing the risk of osteoporosis in their later life. Children
      require higher calcium consumption per body weight than adults, and also
      establish their dietary pattern in this period. MILO has attracted widespread
      popularity as a good-taste chocolate-flavored malt drink with balanced nutrients
      for children. We developed FOSHU MILO with fructooligosaccharides (FOS) aiming at
      improving absorption of calcium, which is originally rich in the products. Using
      the calcium stable isotope (44)Ca, we found that the urinary excretion in the
      subject fed the products with FOS was higher than that of control product without
      FOS, suggesting that the FOSHU MILO is effective in promoting calcium absorption
      from the intestines. MILO could contribute to bone health by increasing
      consumption of calcium and/or improving the calcium bioavailability.

PMID- 17012826
TI  - [Prevention of osteoporosis by foods and dietary supplements. "Kinnotsubu
      honegenki": a fermented soybean (natto) with reinforced vitamin K2 (menaquinone
      7)].
AB  - In recent years, it has been proven that vitamin K(2) has important roles not
      only in blood coagulation but also in bone metabolism. We developed a Bacillus
      subtilis (natto) strain with high productivity of vitamin K(2) (Menaquinone-7),
      and commercialized a natto with reinforced vitamin K(2) by use of the strain. The
      natto, named "Kinnotsubu honegenki", was granted a health claim based on our
      clinical studies which demonstrated that intake of the natto stimulated gamma
      carboxylation of osteocalcin.

PMID- 17012827
TI  - [Role of the type 3 sodium-dependent phosphate transporter in the calcification
      of growth plate chondrocytes].
AB  - Phosphate is a second most abundant mineral next to calcium. The facts that
      hypophosphatemia is associated with the retardation of skeletal development and
      phosphate levels increase during endochondral ossification suggest that phosphate
      plays a role in cartilage differentiation. The type 3 sodium-dependent phosphate
      transporter (NPT3) expressed in growth plate chondrocytes transports
      extracellular phosphates into the cells. These phosphates are utilized for ATP
      synthesis, which in turn promotes apoptosis of growth plate chondrocytes through
      activation of the caspase signal pathways. Subsequently, matrix vesicles released
      from apoptotic chondrocytes accelerate calcification of chondrocytes. Our results
      suggest that phosphate plays a critical role in terminal differentiation of
      chondrocytes.

PMID- 17012828
TI  - [Recent advances in cartilage metabolism research].
AB  - The past few years have seen an enormous increase in the knowledge of the
      signaling pathways and the transcription factors that control endochondral bone
      development. Recent studies of rare chondrodysplasias that exhibit
      disproportionate dwarfism due to the impairment of endochondral ossification have
      identified many responsible genes and have clarified pathogenic mechanisms of
      these diseases by using molecular genetics and biology. The details of human
      diseases related to collagen type II alpha1 (COL2A1), collagen type X alpha1
      (COL10A1), parathyroid hormone (PTH) /parathyroid hormone-related protein (PTHrP)
      receptor, guanylate cyclase B (GC-B), sry-box 9 (SOX9), runt-related
      transcription factor 2 (RUNX2), which play important roles in the process of
      endochondral ossification, will be outlined.

PMID- 17012829
TI  - [Up-date of cartilage repair technique].
AB  - There are two major conditions which require cartilage repair, one is partial
      cartilage defect due to trauma or osteochondritis dissecanse and the other is
      cartilage degeneration and loss induced by osteoarthritis. In this section, we
      introduce several surgical techniques which are available in clinical cases. In
      patient with relatively small traumatic cartilage defect, microfracture
      technique, autologous osteochondral graft transplantation, or autologous cultured
      chondrocytes transplantation are performed. In patients with osteoarthritis,
      which usually larger region is affected than traumatic cartilage defect, cell
      based technique and osteochondral transplantation are not sufficient to cover the
      region, therefore abrasion arthroplasty is performed accompanied with osteotomy
      to correct mechanical property in the joint.

PMID- 17012830
TI  - Atg26 is not involved in autophagy-related pathways in Saccharomyces cerevisiae.
AB  - Autophagy is a degradative pathway conserved among eukaryotes. It is a major
      route for degradation of long-lived proteins and entire organelles, such as
      peroxisomes. Atg26, a sterol glucosyltransferase, is specifically required for
      micro- and macropexophagy, but not for starvation-induced bulk autophagy in
      Pichia pastoris. Here we study the requirement of Saccharomyces cerevisiae Atg26
      in the Cvt pathway, nonspecific autophagy and pexophagy. Our results show that
      the S. cerevisiae atg26Delta strain is not defective in prApe1 maturation,
      macroautophagy or peroxisome degradation, in contrast to the situation seen in
      Pichia pastoris. These studies highlight the importance of examining mutants in
      multiple organisms.

PMID- 17012831
TI  - Pathophysiology of bone metastases.
AB  - Normal bone remodeling maintains an appropriate balance between the action of
      osteoclasts (bone-resorbing cells) and osteoblasts (bone-forming cells). Skeletal
      malignancies, including bone metastases, disrupt the OPG-RANKL-RANK signal
      transduction pathway and promote enhanced osteoclast formation, thereby
      accelerating bone resorption and inducing bone loss. This osteolysis in turn
      leads to the release of bone-derived growth factors, contributing to a "vicious
      cycle" in which interactions between tumor cells and osteoclasts not only lead to
      increased osteoclastogenesis and osteolytic activity, but also aggressive growth
      and behavior of the tumor cells. The osteolytic complications associated with
      bone metastases are caused by tumor-induced alterations of the OPG-RANKL-RANK
      system, which are accompanied by enhanced bone resorption and disassociated from
      counterbalancing bone formation by osteoblasts.

PMID- 17012832
TI  - Autophagy and CD4+ T lymphocyte destruction by HIV-1.
AB  - The first step of HIV-1 infection is mediated by the binding of envelope
      glycoproteins (Env) to CD4 and two major coreceptors, CCR5 or CXCR4. The HIV-1
      strains that use CCR5 are involved in primo-infection whereas those HIV-1 strains
      that use CXCR4 play a major role in the demise of CD4+ T lymphocytes and a rapid
      progression toward AIDS. Notably, binding of X4 Env expressed on cells to CXCR4
      triggers apoptosis of uninfected CD4+ T cells. We now have just demonstrated
      that, independently of HIV-1 replication, transfected or HIV-1-infected cells
      that express X4 Env induce autophagy and accumulation of Beclin 1 in uninfected
      CD4+ T lymphocytes via CXCR4. Moreover, autophagy is a prerequisite to Env
      induced apoptosis in uninfected bystander T cells, and CD4+ T cells still undergo
      an Env-mediated cell death with autophagic features when apoptosis is inhibited.
      To the best of our knowledge, these findings represent the first example of
      autophagy triggered through binding of virus envelope proteins to a cellular
      receptor, without viral replication, leading to apoptosis. Here, we proposed
      hypotheses about the significance of Env-induced Beclin 1 accumulation in CD4+ T
      cell death and about the role of autophagy in HIV-1 infected cells depending on
      the coreceptor involved.

PMID- 17012833
TI  - Clonal heterogeneity of tumor may be due to continuous influx of newly
      transformed cells.

PMID- 17012834
TI  - The quantification of PSA mRNA copies in pathologically normal pelvic lymph nodes
      is a viable prognostic indicator.
AB  - Localized prostate cancer is a disease associated with significant biochemical
      recurrence with rising serum prostate-specific antigen (PSA) levels and marked
      progression. More specific prognostic methods are needed to identify the occult
      micrometastases that lead to biochemical recurrence. Ferrari et al. report on the
      technique of quantifying pathologically occult metastases in pelvic lymph nodes
      via PCR quantification. The group reports statistically significant biochemical
      failurefree recurrence in the comparison of 100 or greater normalized PSA mRNA
      copies (PSA-N) versus PSA-N of less than 100 at a median follow up of four years.
      PSA-N quantification appears to be an important method for predicting biochemical
      recurrence and characterizing the recurrence risk of localized prostate cancer
      patients with pathologically normal pelvic lymph nodes. This method warrants
      further investigation in prospective trials.

PMID- 17012835
TI  - Photochemically mediated delivery of AdhCMV-TRAIL augments the TRAIL-induced
      apoptosis in colorectal cancer cell lines.
AB  - Tumor targeting is an important issue in cancer gene therapy. We have developed a
      light-specific transduction method, named photochemical internalization (PCI), to
      enhance gene expression from adenoviral vectors selectively in illuminated areas.
      Tumor necrosis factor related apoptosis inducing ligand (TRAIL) has been shown to
      induce apoptosis in cancer cells, and the aim of this study was to investigate
      the potential of PCI to enhance transgene expression from AdhCMV-TRAIL and
      evaluate its impact on apoptotic induction in the two human colorectal cancer
      cell lines HCT116 and WiDr. PCI-mediated delivery of AdhCMV-TRAIL enabled an
      increased expression of TRAIL, induced a synergistic reduction in cell viability
      compared to the individual action of AdhCMV-TRAIL and photochemical treatment,
      and enhanced the induction of apoptosis demonstrated by an increase in
      cytoplasmic histone-associated DNA fragments, caspase-8 and caspase-3 activation,
      PARP cleavage and a decrease in the mitochondrial membrane potential. The
      synergistic effect could be related to the enhanced TRAIL expression in PCI
      treated samples and a modest sensitization of the cancer cells to TRAIL induced
      apoptosis due to the photochemical treatment. Furthermore, an increased cleavage
      of Bid and a cell line dependent reduction in the expression levels of anti
      apoptotic Bcl-2 family members were observed and could possibly contribute to the
      enhanced apoptotic level in samples exposed to the combined treatment. The
      presented results indicate that photochemically mediated delivery of AdhCMV-TRAIL
      allows a selective enhancement in cell killing, and suggest that PCI may be
      relevant and advantageous for therapeutic gene delivery in vivo.

PMID- 17012836
TI  - Differentiating pancreatic lesions by microarray and QPCR analysis of pancreatic
      juice RNAs.
AB  - BACKGROUND: The gene expression profile of pancreatic cancer is significantly
      different from that of normal pancreas. Differences in gene expression are
      detectable using microarrays, but microarrays have traditionally been applied to
      pancreatic cancer tissue obtained from surgical resection. We hypothesized that
      gene expression alterations indicative of pancreatic cancer can be detected by
      profiling the RNA of pancreatic juice. METHODS: We performed oligonucleotide
      microarray analysis on RNA isolated from pancreatic juice obtained endoscopically
      after secretin stimulation from six patients with pancreatic cancer and ten
      patients with nonneoplastic diseases of the pancreas or upper gastrointestinal
      tract. Extracted RNA was subjected to two rounds of linear RNA amplification, and
      then hybridized with U133A or X3P gene chips (Affymetrix). RESULTS: Using the
      U133A or X3P chips, 37 and 133 gene fragments respectively, were identified as
      being at least 3-fold more abundant in the pancreatic juice of patients with
      pancreatic cancer compared to the noncancer controls (p<0.05, Mann-Whitney test).
      For example, pancreatic juice from patients with pancreatic cancer contained
      increased levels of IL8, IFITM1, fibrinogen, osteopontin, CXCR4, DAF and NNMT
      RNA, genes that have been previously reported as overexpressed in primary
      pancreatic cancers or pancreatic cancer cell lines relative to control tissues.
      CONCLUSIONS: These results demonstrate that RNA analysis of pancreatic juice can
      reveal some of the same RNA alterations found in invasive pancreatic cancers. RNA
      analysis of pancreatic juice deserves further investigation to determine its
      utility as a tool for the evaluation of pancreatic lesions.

PMID- 17012837
TI  - Aging and immortality: quasi-programmed senescence and its pharmacologic
      inhibition.
AB  - While ruling out programmed aging, evolutionary theory predicts a quasi-program
      for aging, a continuation of the developmental program that is not turned off, is
      constantly on, becoming hyper-functional and damaging, causing diseases of aging.
      Could it be switched off pharmacologically? This would require identification of
      a molecular target involved in cell senescence, organism aging and diseases of
      aging. Notably, cell senescence is associated with activation of the TOR (target
      of rapamycin) nutrient- and mitogen-sensing pathway, which promotes cell growth,
      even though cell cycle is blocked. Is TOR involved in organism aging? In fact, in
      yeast (where the cell is the organism), caloric restriction, rapamycin and
      mutations that inhibit TOR all slow down aging. In animals from worms to mammals
      caloric restrictions, life-extending agents, and numerous mutations that increase
      longevity all converge on the TOR pathway. And, in humans, cell hypertrophy,
      hyper-function and hyperplasia, typically associated with activation of TOR,
      contribute to diseases of aging. Theoretical and clinical considerations suggest
      that rapamycin may be effective against atherosclerosis, hypertension and hyper
      coagulation (thus, preventing myocardial infarction and stroke), osteoporosis,
      cancer, autoimmune diseases and arthritis, obesity, diabetes, macula
      degeneration, Alzheimer's and Parkinson's diseases. Finally, I discuss that
      extended life span will reveal new causes for aging (e.g., ROS, 'wear and tear',
      Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi
      programmed senescence kills us first.

PMID- 17012838
TI  - Reactivation of p53 function with a demethylating agent.

PMID- 17012839
TI  - A novel non-invasive biomarker for assessment of small intestinal mucositis in
      children with cancer undergoing chemotherapy.
AB  - BACKGROUND: Small intestinal mucositis is a common side-effect following high
      dose chemotherapy, causing patients to experience pain and abdominal
      complications often leading to extended stays in hospital. A biomarker to detect
      these small intestinal changes does not exist in clinical practice. This study
      aimed to assess the noninvasive 13C-Sucrose breath test (SBT) to detect small
      intestinal damage associated with mucositis in pediatric cancer patients having
      chemotherapy. PATIENTS AND METHODS: Small intestinal function was assessed in 15
      pediatric cancer patients and 26 healthy children. Subjects were studied for
      small intestinal permeability (SIP; lactulose/rhamnose), digestive and absorptive
      capacity (SBT; sucrose), and oro-cecal transit time (OCTT; lactulose), by
      ingesting two sugar drinks containing the respective sugars. Combined tests were
      carried out at baseline, day 1, day 3-5 and day 6-9, and in healthy individuals
      on two separate occasions. A total of 25 cycles of chemotherapy were assessed.
      Breath samples for the SBT were collected every 15 min for 3 h (expressed as %
      cumulative dose at 90 min (CD)), a 5 h urine collection for SIP and breath
      hydrogen determined every 30 min for three hours for OCTT. RESULTS: Clinical
      mucositis occurred in seven of the 25 cycles of chemotherapy (28%). No
      significant difference was observed for SIP and OCTT. The SBT %CD at 90 min was
      significantly lower in the mucositis group compared to the unaffected group and
      controls at baseline (p<0.05). Patients who developed mucositis maintained a
      significantly lower %CD, for all test points (p<0.05) compared to the unaffected
      patients. In patients who developed mucositis the SBT was below the reference
      range of the controls at all time points. CONCLUSION: The findings show for the
      first time that it is possible to noninvasively detect and monitor gut damage
      associated with chemotherapy-induced mucositis in pediatric cancer patients.

PMID- 17012840
TI  - Regulation of MAP kinases by the VHR dual-specific phosphatase: implications for
      cell growth and differentiation.
AB  - Although it is well established that a transient activation of the mitogen
      activated protein kinases Erk and Jnk is a crucial step in most growth promoting
      signaling pathways, it has also been demonstrated that a prolonged activation of
      these kinases can induce differentiation, cell cycle arrest, and cell senescence.
      We recently found that the expression of the 21-kDa human Vaccinia H1-related
      (VHR) dual-specific phosphatase fluctuates during cell cycle progression and
      affects Erk and Jnk activity in a cell cycle-dependent manner. Cells lacking VHR
      arrested at the G(1)/S and G(2)/M transitions of the cell cycle and exhibited
      senescence phenotypes. Cells lacking VHR upregulated p21(Cip/Waf1) and
      downregulated many genes for cell cycle regulators, DNA replication,
      transcription, and mRNA processing. In the absence of VHR, the serum-induced
      activation of Jnk and Erk was further elevated and was required for the G(1)/S
      and G(2)/M blocks, which were attenuated upon Jnk and Erk inhibition.
      Collectively, VHR provides a long sought layer in the regulation of Jnk and Erk
      during cell cycle progression thereby contributing to cell cycle arrest,
      differentiation or senescence.

PMID- 17012841
TI  - Enhanced specificity of the p53 family proteins-based adenoviral gene therapy in
      uterine cervical cancer cells with E2F1-responsive promoters.
AB  - p63 and p73, the p53 family proteins, are similar to p53 in many aspects:
      structural homology, transactivation of p53-downstream genes, and induction of
      apoptosis. Interestingly, they also differ from p53; in particular, they are not
      inhibited by viral oncoproteins such as HPV E6. This feature would be an
      advantage over p53 in HPV-associated cancers and therefore, we evaluated the
      therapeutic potentials of various p53 family proteins (p73alpha, p73beta,
      p63alpha and p63gamma) against HPV-infected cervical cancers. In clonogenic
      assay, exogenous expression of p73alpha, p73beta and p63gamma inhibited the
      colony formation of HPV-positive cervical cancer cells under G418- selection
      while p53 could not. Recombinant adenoviruses Ad/CMVp73alpha, Ad/CMVp73beta and
      Ad/CMVp63gamma induced potent apoptosis in all infected cervical cancers (CasKi,
      SiHa, HeLa, C33A, SNU682, SNU17, SNU1005, SNU703), irrespective of their HPV
      infection status. Unfortunately however, Ad/CMVp73alpha, Ad/CMVp73beta, and
      Ad/CMVp63gamma inhibited also normal cells such as endothelial cells,
      fibroblasts, and keratinocytes thus, tumorspecific promoter was indispensable to
      the p53 family proteins-based therapy. Here we report a stringent tumor killing
      by p73beta in combination with ESM6, a synthetic promoter targeting the DNA tumor
      virusassociated cancers. Recombinant adenoviruses encoding p73beta by ESM6
      (Ad/ESM6p73beta and Ad/ESM6p73bENH) expressed p73beta and induced apoptosis only
      in the cancer cells but not in normal cells. Collectively, we suggest that the
      p53 family proteins are potent therapeutic agents for HPV-associated uterine
      cervical cancers and ESM6 mediated expression of the p53 family proteins would be
      a safe and strong tumor targeting strategy.

PMID- 17012842
TI  - BRCA mutations and childhood cancer.

PMID- 17012843
TI  - Myc overexpression enhances apoptosis induced by small molecules.
AB  - The Myc oncogene is deregulated in a wide variety of human tumors hence the Myc
      pathway is an attractive target for tailored cancer treatment. We have recently
      identified two small molecules, MYRAs (Myc-pathway response agents), that induce
      apoptosis in a Myc-dependent manner and inhibit Myc-driven transformation. Here,
      we show that these compounds in addition have prominent effects in MYCN
      overexpressing neuroblastoma cells. A third compound, NSC308848, also induced
      apoptosis in Myc-overexpressing cells and inhibited Myc-induced cellular
      transformation. However, in contrast to the MYRAs, NSC308848 treatment resulted
      in decreased Myc protein levels and gave rise to inhibitory effects also on other
      transcription factors than Myc. Taken together, our findings suggest that these
      three small molecules can elicit a similar biological response by interfering
      with the Myc pathway at different levels.

PMID- 17012844
TI  - Stem cells, differentiation and cancer: mentors, colleagues and academic
      administration.

PMID- 17012845
TI  - Histamine-mediated signaling processes in human malignant mammary cells.
AB  - Histamine is a biogenic amine responsible for multiple biological actions
      including regulation of physiological functions of mammary gland. It has been
      postulated that histamine plays a critical role in proliferation of normal and
      cancer cells. To investigate the biological responses that histamine exerts in
      malignant cells derived from human mammary gland, we evaluated in MDA-MB-231 line
      the expression of histamine receptors, histamine intracellular content, the
      capacity of histamine to influence proliferation, cell cycle progression,
      differentiation and apoptosis. We also studied histamine involvement in cellular
      response to ionizing radiation. HBL-100 cells were used as control of non
      tumorigenic breast cells. Proliferation and surviving fraction were assessed by
      clonogenic assay. Cell cycle progression and lipid accumulation were determined
      by flow cytometry while apoptosis was studied by Annexin V and DNA fragmentation
      assays. Both cell lines expressed the four histamine receptors subtypes as
      evaluated by western blot and RT-PCR analyses, and present endogenous histamine.
      Histamine regulated proliferation of cancer cells in a dose-dependent way and 10
      microM histamine reduced significantly proliferation to 23% inducing cell cycle
      arrest in G(2)/M phase, differentiation by 26% and a significant increase in the
      number of apoptotic cells (p < 0.01). These responses were not observed in HBL
      100 cells. Furthermore, 10 microM histamine exclusively enhanced the
      radiosensitivity of MDA-MB-231 cells. These results represent the first report
      about the expression of H3 and H4 receptors in human breast cells. In addition,
      we conclude that histamine exerts different effects on biological responses of
      normal and cancer breast cells representing a promising target for the
      development of more specific and less toxic cancer therapies.

PMID- 17012846
TI  - Epigenetic activation of tumor suppressor microRNAs in human cancer cells.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous post
      transcriptional silencers of target genes. miRNAs are expressed in a tissue
      specific manner and play important roles in cell proliferation, apoptosis and
      differentiation during animal development. Recent studies have shown a distinct
      connection between aberrant expression of miRNAs and the development of cancer,
      suggesting that miRNAs can be potential therapeutic targets. Our recent study has
      shown that some miRNAs are controlled by epigenetic alterations such as DNA
      methylation and histone modification in human cancer cells. Activation of tumor
      suppressor miRNAs by chromatin modifying drugs may cause downregulation of target
      oncogenes and could be a novel strategy for the prevention and treatment of human
      cancer.

PMID- 17012847
TI  - Sucrose breath testing and intestinal mucositis.

PMID- 17012848
TI  - MicroRNAs: a new insight into cancer genome.
AB  - Cancer is a disease involving multi-step dynamic changes in the genome. However,
      studies on cancer genome so far have focused most heavily on protein-coding
      genes, and our knowledge on alterations of the functional noncoding sequences in
      cancer is largely absent. MicroRNAs (miRNA) are approximately 22 nt noncoding
      RNAs, which regulate gene expression in a sequence-specific manner via
      translational inhibition or mRNA degradation. Mounting evidence is showing that
      miRNAs may play important roles in tumor development, and a better understanding
      of their alteration in cancer genome and oncogenic property should contribute to
      the diagnosis and treatment of cancer.

PMID- 17012849
TI  - New tools for dissecting RON receptor tyrosine kinase oncogenic signaling.

PMID- 17012850
TI  - Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production
      of reactive oxygen species by the mitochondrial voltage-dependent anion channel.
AB  - The mitochondrial production of reactive oxygen species has been implicated in
      the anticancer activity of furanonaphthoquinone. However, the mechanism of the
      activation remains elusive. In the current study, we found that treatment of HeLa
      cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces
      mitochondrial swelling, followed by apoptosis. This toxic effect of FNQ13 was
      reduced by the radical scavengers alpha-tocopherol and trolox. Cytochemical
      experiments in isolated mitochondria showed that a combination of FNQ13 and NADH
      induces the production of H(2)O(2) at the exterior mitochondrial membrane
      surface. This production of H(2)O(2) was reduced by an antibody to the voltage
      dependent anion channel (VDAC). Overexpression of the VDAC by transfection with
      vdac1 cDNA increased the production of H(2)O(2) by HeLa cells, whereas
      transfection with a small interfering RNA to VDAC reduced FNQ13-induced H(2)O(2)
      production and cell death due to an almost complete knockdown of VDAC expression.
      We also found significant correlations between the expression of VDAC and the
      induction of H(2)O(2) production and cell death by FNQ13 in 11 human cancer cell
      lines. These results indicate that the anticancer activity of
      furanonaphthoquinones depends on the production of reactive oxygen species by
      mitochondrial permeability transition pores including the VDAC.

PMID- 17012851
TI  - Towards an epitope-based human vaccine for influenza.
AB  - The conventional, currently available vaccines against influenza virus, though
      quite successful, suffer from a few shortcomings; one major limitation is their
      restriction to the specific strains that are included in the vaccine. We review
      herewith some of the more recently developed influenza vaccines and further
      describe our own results on the design of epitope-based vaccine for human use. In
      this vaccine, a combination of B- and T-cell epitopes are individually expressed
      within an immunogenic molecule--salmonella flagellin--and the resultant
      recombinant flagella serve both as a carrier and as an adjuvant. The mixture of
      recombinant flagella expressing the appropriate epitopes was administered to
      young and aged mice as well as to human/mouse chimera model in which human PBMC
      are functioning within the mice body. Intranasal immunization in all these animal
      models led to effective protection against challenge infection with different
      strains of influenza virus.

PMID- 17012852
TI  - Taming NEMO to slay cancer cells.
AB  - In order to increase the efficacy of chemotherapy, it is necessary to first
      understand the forces that act to promote cell survival in the face of cellular
      damage. The NF-kappaB pathway plays a clear role in mediating cell survival in
      response to DNA damage, acting in opposition to pro-apoptotic signals. How this
      pathway is regulated has been less clear. Recent studies have shed light on the
      intersection of DNA damaging pathways and the NF-kappaB signal transduction
      cascade. Wu and colleagues (Science 2006; 311:1141-6) demonstrate that ATM
      directly phosphorylates NEMO in response to DNA damage. ATM then is carried into
      the cytoplasm with NEMO allowing for the activation of IKK and thus NF-kappaB
      activation.

PMID- 17012853
TI  - A new marine-derived sulfated polysaccharide from brown alga suppresses tumor
      metastasis both in vitro and in vivo.
AB  - Herein, we report that marine-derived sulfated polysaccharide (MSP), a new kind
      of polysaccharide extracted from brown alga, exhibits the anti-migration effect
      in vitro and potently suppress metastasis of Lewis lung carcinoma in vivo.
      Adhesion assays demonstrated that MSP inhibits the heterogenous adhesion on
      fibronectin. Further studies revealed that MSP decreased FN-induced MDA-MB-435
      migration, accompanied by its potent regulatory effect on actin filament
      reassembling. In addition, MSP significantly inactivated the phosphorylation of
      FAK and subsequent ERK1/2 in MDA-MB-435 cells. All these actions may be the
      results of MSP binding to FN, promising the therapeutic potential of MSP in tumor
      metastasis.

PMID- 17012854
TI  - Cutaneous delivery of a live, attenuated chimeric flavivirus vaccine against
      Japanese encephalitis (ChimeriVax)-JE) in non-human primates.
AB  - Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue
      hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an
      urgent need for alternative technologies for mass vaccination against these and
      other diseases, particularly in the developing world. Here, we administered a
      live attenuated, chimeric JE vaccine (ChimeriVax)-JE) to nonhuman primates by
      skin microabrasion and intradermal delivery using microneedles. Both cutaneous
      delivery methods induced mild viremia similar in magnitude to that observed
      following subcutaneous (SC) injection. The duration of viremia induced by
      cutaneous delivery (5-7 days), however, was substantially longer than via SC (0-3
      days). In addition, mean neutralizing antibody titers in cutaneous delivery
      groups were up to 7-fold greater than via SC injection. There were no safety
      issues identified and both cutaneous delivery methods appeared to be well
      tolerated. Thus, cutaneous delivery may represent a minimally-invasive
      alternative approach for flavivirus vaccines that more closely resembles the
      natural route of viral infection.

PMID- 17012855
TI  - Silencing stathmin gene expression by survivin promoter-driven siRNA vector to
      reverse malignant phenotype of tumor cells.
AB  - Stathmin gene overexpression has been shown to play an important role in
      maintenance of malignant phenotype in tumor cells, and the blocking efficacy and
      tumor specificity of this target has been concerned in clinical trails. In this
      report, we designed survivin promoter-driven siRNA eukaryotic expression vector
      that expressed the small interfering RNA targeting stathmin gene to selectively
      knock down the stathmin gene expression in two different kinds of tumor cell
      lines while sparing normal cell lines. The therapeutic potential of this
      recombinant vector was tested in human cervical cancer Hela cells and
      osteosarcoma SSOP-9607 cells, and in human umbilical vein endothelial cell line
      ECV304 cells as control. The siRNA vector- transfected Hela cells and SSOP-9607
      cells revealed marked inhibition of stathmin expression and a dramatic growth
      inhibition comparing with ECV304 cells, parental-vector transfected cells and
      untransfected cells. Cell cycle analysis of siRNA vector transfected tumor cells
      by Flow Cytometry showed G(2)/M phase block, while morphologic analysis by TURNEL
      staining method showed marked increase of apoptosis. Our study indicates that
      survivin gene promoter-driven stathmin siRNA expression vector may have potential
      use in tumor gene therapy with targeted tumor gene silencing effect.

PMID- 17012856
TI  - Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of
      humoral and cellular responses after vaccination in the Sprague Dawley rat.
AB  - The recombinant larval protein Na-ASP-2 from the human helminth parasite Necator
      americanus is a lead candidate for a human hookworm vaccine. We have
      characterized the humoral and cellular immune responses elicited by the Na-ASP-2
      formulated with the aluminum-based adjuvant Alhydrogel in the Sprague Dawley rat.
      We demonstrated that Na-ASP-2 vaccine induced a strong antibody response at all
      doses tested, as evidenced by high specific IgG1, IgG2a and IgM titers. High IgG
      antibody titers were maintained up to three months post vaccination and were
      boosted by an additional vaccine dose. Specific cell proliferation and a Th2
      cytokine profile were also observed in peripheral blood of all rats immunized
      with the formulated vaccine. Host IL-6 levels were also significantly elevated.
      These data provide evidence that the immune response of the Na-ASP-2 vaccine is
      robust and durable and therefore suitable for the further clinical development of
      the Na-ASP-2 vaccine.

PMID- 17012857
TI  - Seroprevalence of varicella among children and adolescents in Valencia, Spain.
      Reliability of the parent's reported history and the medical file for
      identification of potential candidates for vaccination.
AB  - This study assessed the seroprevalence of varicella antibodies in children and
      adolescents in Spain and evaluated the reliability of two methods for detecting
      susceptible individuals: (1) parental-reported history of varicella and (2)
      medically-documented histories maintained by the pediatrician. A total of 186
      children (6 to 15 years of age) were recruited in 13 pediatric offices of
      Valencia, Spain. A brief case report form was completed including previous
      history of varicella referred by the parents, and a 5 mL blood sample was
      obtained. The pediatrician medical file was reviewed for antecedent of varicella.
      The overall prevalence of varicella antibodies was 84% and 88% in the 6-9 years
      and 10-15 years age brackets, respectively. The predictive value of a negative
      history of varicella disease was 48% by parental recall (52% "false negative"),
      and only 26% by medical record (74% "false negative"). However, the positive
      predictive value of a positive parental reported history or a positive medically
      documented history was 95%. The most effective strategy for varicella vaccination
      of older children and adolescents in Spain will be to immunize those individuals
      with a lack of positive (unknown or negative) history of disease.

PMID- 17012858
TI  - Beveled needle technique is not associated with low "take" rates in Israeli
      smallpox revaccination campaign.
AB  - BACKGROUND: In its first large-scale smallpox vaccination campaign in the 20(th)
      century, Israel has experienced an exceptionally high rate of failure to achieve
      clinical take following vaccination. It was hypothesized that this failure rates
      might be attributed to the unique vaccination technique adopted in Israel, of
      using beveled needles rather than bifurcated needles. MATERIALS AND METHODS: We
      retrospectively identified two cohorts vaccinated in the defined dates during the
      Israeli revaccination campaign, in which beveled needles and bifurcated needles
      were used alternately, and studied the impact of different covariates on clinical
      vaccination outcome measures. RESULTS: Of 116 subjects that were vaccinated
      within the defined dates, 46 were vaccinated using bifurcated needles, and 70 by
      beveled needles. 'Take' rates in subjects vaccinated up to 20 years earlier was
      77.5%, compared with 97.2% among those vaccinated in the more distant past (p =
      0.001). In multivariate analyses, vaccination 'take' was independently associated
      with a shorter time from previous vaccination (p = 0.013), but not with gender,
      birth country, vaccinator or the vaccination technique used. CONCLUSIONS: The low
      take rates observed in the Israeli smallpox revaccination campaign could not be
      attributed to the unique local vaccination technique, and was most likely induced
      by a higher rate of residual immunity among vaccinees, compared with the US, as
      well as by the lower vaccine concentrations used in Israel. In countries and
      circumstances when bifurcated needles are not sufficiently available, the beveled
      needle technique may be considered an appropriate alternative.

PMID- 17012859
TI  - Potency of cell-mediated immune responses to different combined HIV-1 immunogens
      in a humanized murine model.
AB  - In this study, cell-mediated immune responses were evaluated in HLA-A2.1 mice
      that received polycistronic vector expressing HIV-1 gp120, gag and pol or single
      vectors expressing gp120 + gag/pol as well as recombinant structural proteins and
      adjuvants. Mice primed with the polycistronic DNA/CpG and boosted with the same
      regimen plus proteins induced a higher T-cell proliferative response to gp120.
      However, a very high frequency of IFN-gamma was detected in mice receiving the
      mixture of gp120 + gag/pol DNA constructs, recombinant proteins and CpG. We also
      measured specific CD8+T cells in PBMCs by intracellular cytokine and HLA-A2.1
      peptide dimer staining in response to HLA-A2.1-restricted HIV-1 epitopes (gp120,
      gag and pol). The group that received single gp120 + gag/pol DNA constructs,
      recombinant proteins and CpG had a higher CD8+T cell response to the combination
      of peptides compared to the other groups that received the polycistronic
      construct. The present study reveals an optimal combination of immunogens to
      enhance immune responses against HIV-1.

PMID- 17012860
TI  - A new DTPw-HBV/Hib vaccine is immunogenic and safe when administered according to
      the EPI (Expanded Programme for Immunization) schedule and following hepatitis B
      vaccination at birth.
AB  - New combination vaccines and reliable sources of vaccine components are essential
      to ensure the success of mass immunisation programmes in the 21st century. We
      evaluated a new combined diphtheria-tetanus-whole-cell-pertussis-hepatitis B
      vaccine, extemporaneously mixed with a Haemophilus influenzae type b conjugate
      vaccine (DTPw-HBV/Hib) containing 2.5 microg PRP in 913 Philippino infants,
      administered according to the EPI schedule at 6, 10 and 14 weeks of age after a
      birth dose of hepatitis B vaccine (HBV; trial DTPw-HBV/Hib-001). One month after
      the third dose of DTPw-HBV/Hib (N = 182), 99.4% and 94.2% of subjects had anti
      PRP antibody levels > or =0.15 microg/mL and > or =1.0 microg/mL, respectively.
      In addition, 95.9%, 100.0% and 87.6% of subjects had seroprotective antibody
      concentrations against diphtheria, tetanus and hepatitis B, respectively. The
      seroprotection rate to hepatitis B increased significantly to 94.3% in subjects
      who received a dose of HBV at birth. The pertussis vaccine response rate was > or
      =95%. Seroprotection/vaccine response rates to all antigens after DTPw-HBV/Hib
      were at least as good as those observed after vaccination with GSK Biologicals'
      licensed Tritanrix HepB/Hiberix (containing 10 microg PRP) which was used as
      comparator. Although redness >20 mm in diameter and fever > or = 37.5 degrees C
      (axillary route) occurred more often after the new DTPw-HBV/Hib vaccine (p <
      0.05), other Grade 3 adverse events occurred similarly between the groups. The
      new DTPw-HBV/Hib vaccine was as immunogenic and well tolerated as the licensed
      control vaccine when administered according to the immunologically challenging
      EPI schedule. A birth dose of HBV is important to maximize protection against
      hepatitis B in endemic regions where the EPI schedule is in place.

PMID- 17012861
TI  - The natural history of untreated HIV infection in Lima, Peru: implications for
      clinical trial endpoints for HIV vaccines.
AB  - Most candidate HIV vaccines are directed at priming memory T cell responses and
      are being evaluated on their effects on post acquisition viremia and/or disease
      progression. These vaccines are being studied in areas of high HIV-1 prevalence.
      As such, we evaluated the frequency of CD4+ T cell decline and time course of
      opportunistic infections of patients presenting at a major metropolitan hospital
      in Lima, Peru, an area where such candidate vaccines are being tested. We
      examined 92 patients with untreated HIV-1 in calendar year 2002: 35% presented
      with CD4+ T cell counts of <200, 25% between 201 and 400, and 17% with >400
      cells/mm3, 30 of 92 patients presented with overt AIDS, 6 were without an AIDS
      defining OI but CD4 counts <200. Over the course of follow-up, CD4 count
      decreased by a mean of 31 cells/mm3/year in women and 28 in men (p>0.5). Among
      persons presenting with CD4 counts >250 cells/mm3, the median time to first OI
      was 3.5 years. If clinical endpoints are required to evaluate the clinical
      effectiveness of T cell based vaccines, extended clinical follow-up of subjects
      enrolled in such trials will be required.

PMID- 17012862
TI  - Follow-up of MMR vaccination status in children referred to a pediatric
      immunization clinic on account of egg allergy.
AB  - OBJECTIVE: To determine timeliness and completeness of MMR immunization uptake
      and general immunization status of egg-allergic children referred to hospital for
      MMR vaccine who were referred back to their primary care providers with
      explanatory information that community-based vaccination is safe in these
      children. METHOD: Referred children's immunization status obtained from referring
      practices. Where the practice had no record parents were contacted. Parents whose
      children had not received MMR were asked reasons for their choice. Timeliness of
      immunizations was examined for both MMR and the primary schedule. Practices
      referring more than one child to immunization clinic were analysed to determine
      whether previous letters from the immunization clinic influenced their referring
      practice. RESULTS: 82 children were eligible from 67 practices. MMR status was
      obtained for 78 (95% response rate). Of these 78, 73 (94%) received MMR
      vaccination with no reported adverse events: 8 (11%) on time, 54 (69%) late and
      11 (14%) timeliness unknown. Five (6%) children had not received MMR vaccination.
      Three practices were unwilling to carry out MMR immunization of egg-allergic
      children, even after recommendation from the immunization clinic. Of the five
      parents whose children had not received MMR, two had actively decided against
      vaccination. DISCUSSION: 94% children received their MMR in primary care with no
      reported adverse effects. The current strategy utilised by the immunization
      clinic appears to result in MMR immunization of egg-allergic children. While the
      referral process may result in delayed immunizations, continued education of
      health professionals may improve timeliness and immunization rates.

PMID- 17012863
TI  - Randomized, placebo-controlled, phase I/IIa evaluation of the safety and
      immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in
      HIV-1 infected subjects.
AB  - We conducted a randomized, placebo-controlled double-blind trial to examine the
      safety and immunogenicity of a candidate HIV therapeutic vaccine based upon a
      recombinant fowl pox virus capable of coexpressing the human cytokine interferon
      gamma and/or genes from HIV-1. Thirty-five eligible subjects were randomized (12
      placebo, 11 fowlpox + HIV genes, 12 fowl pox + HIV genes + interferon gamma). All
      but one subject (placebo group) received three immunizations (by intramuscular
      injection on day 0, week 4 and week 12) and all completed 52 weeks of follow-up.
      All subjects continued to take combination antiretroviral therapy for the
      duration of study. There were no significant toxicity or safety concerns and the
      distribution of adverse events and their severity was consistent across each
      randomly assigned vaccine group. Comparison of placebo recipients with the
      combined recipients of the two vaccine constructs, in terms of anti-HIV gag
      ELISpot or lymphoproliferative responses, tended to favour the placebo group, but
      were not significantly different (difference in time-weighted mean change from
      baseline = 56 Spot forming units (sfu)/10(6) PBMC; p = 0.062 and 4.4 SI; p =
      0.337). There were no significant changes in CTL responses by standard Cr(51)
      release assay. Anti-FPV antibodies were detected by week 14 in 0 placebo and 20
      (87%) vaccine recipients. Although safe, neither vaccine construct appeared to
      possess detectable T-cell mediated anti-HIV immunogenic properties in HIV
      infected individuals, as measured by standard T cell assays.

PMID- 17012864
TI  - Canadian Association for Immunization Research and Evaluation (CAIRE) guidelines
      for industry-sponsored clinical trial and epidemiology contract research.
AB  - In response to concerns about interactions of academic and public health
      investigators with industry, the Canadian Association for Immunization Research
      and Evaluation (CAIRE), in collaboration with six major vaccine manufacturers,
      developed guidelines for participation in industry-sponsored clinical trial and
      epidemiology contract research within Canada. Topics addressed include definition
      of investigators, data ownership, protocol development, data management, data
      analysis, producing a study report and publication of the results of the study.

PMID- 17012865
TI  - Poliovirus-binding inhibition ELISA for evaluation of immune response to oral
      poliovirus vaccine: a possible alternative to the neutralization test.
AB  - This study describes an ELISA variant (Binding Inhibition ELISA, BI ELISA) for
      the quantitative determination of neutralization-relevant antibodies to
      polioviruses. The test differs from previously described analogs by utilizing
      polyclonal immune reagents: capture antibodies and biotin-labeled detecting
      antibodies. The BI ELISA was compared with the conventional neutralization test
      (NT) by testing live Sabin and wild-type poliovirus strains. The comparison of 68
      serum samples taken from Oral Poliovirus Vaccine (OPV) recipients showed 100%
      specificity and sensitivity for Sabin 1 and Sabin 2, and 100% sensitivity and 97%
      specificity for Sabin 3. Good correlations (r = 0.7, 0.77, 0.65 for Sabin 1, 2,
      3, respectively) were demonstrated between the NT and BI ELISA results. These
      results indicate that the BI ELISA can be used as a reliable alternative to the
      NT for determination of neutralization-relevant antibodies to polioviruses in
      vaccinees and in large-scale sero-epidemiological studies.

PMID- 17012866
TI  - Delivery of influenza vaccine to non-elderly persons with cardiovascular disease,
      with varying national supply of vaccine: a decision analysis.
AB  - Influenza immunization rates among non-elderly persons at high-risk for influenza
      are far below target levels in the United States. Provision of influenza vaccine
      at subspecialty practices can target high-risk patients, particularly during
      influenza vaccine shortages. We conducted a decision analysis to explore the
      potential effects on non-elderly cardiac patients' immunization rates of
      improving vaccine availability, standing orders rates, and physicians' vaccine
      recommendation rates in cardiology, primary care, and other medical subspecialty
      outpatient practices. We considered two supply circumstances (sufficient versus
      50% of needed supply), and also incorporated community and hospital based vaccine
      delivery as well as patient acceptance in the model. With sufficient vaccine
      supply, optimized performance of cardiology practices (maximum vaccine
      availability, strong physician recommendations, and standing orders) yielded
      greater improvement in vaccine coverage rate than with separately optimized
      performance in primary care, pulmonology, or endocrinology practices. With only
      50% of needed vaccine supply, reallocation of doses from community sites to
      primary care and cardiology, pulmonology, and endocrine offices yielded higher
      estimated immunization rates in the target population than strategies without
      reallocation. Only with simultaneous interventions across primary care,
      subspecialty care, inpatient, and community domains did immunization rates exceed
      60%. Targeted interventions to optimize delivery of influenza vaccine in
      cardiology practices may be the most effective means of raising vaccine coverage
      levels among non-elderly cardiovascular patients, in times of varying national
      vaccine supply.

PMID- 17012867
TI  - Yellow fever 17D vaccine safety and immunogenicity in the elderly.
AB  - The incidence of serious and severe multisystem adverse events (AEs) following
      yellow fever (YF) 17D vaccine is higher in persons of advanced age. One
      hypothesis for the occurrence of these AEs in the elderly is immunological
      senescence and a reduced ability to clear the vaccine virus infection. We
      determined age-specific rates of serious and nonserious AEs in two large clinical
      trials of two YF 17D vaccines from different manufacturers. In addition, we
      analyzed AEs reported in a large general practice data base in the United
      Kingdom. Neutralizing antibody responses were compared in young and elderly
      subjects. In the clinical trials, involving a total of 4,532 subjects, there were
      no neurological and viscerotropic AEs; interestingly, the incidence of common
      injection site and systemic AEs was significantly lower in elderly than in
      younger subjects. The neutralizing antibody categorical and quantitative
      responses were equivalent across younger and elderly subjects. In contrast, the
      larger retrospective analysis of 43,555 persons receiving YF 17D in the UK
      general practice database revealed a higher incidence of significant neurologic
      and multisystem AEs with advancing age. The age-specific reporting rate ratio
      (RRR) was approximately twice that in the 25-44 year-old reference group for
      subjects in the 45-64 year age group (RRR 1.82; 95% CI 0.88,3.77) and 3-fold
      higher for the 65-74 year-old age group (RRR 2.82; 95% CI 0.81, 9.81). These
      results are consistent with previous reports on YF vaccine safety in the US
      (Martin M, et al. Emerg Infect Dis 2001;6:945-51; Khromova et al., Vaccine
      2005;23:3256-63). In elderly persons, YF 17D vaccine is associated with a higher
      frequency of significant AEs in the elderly but a lower incidence of common
      nonserious side-effects. The neutralizing antibody response, which is the
      mediator of protective immunity to YF, is not diminished in healthy, elderly
      persons.

PMID- 17012868
TI  - DNA-based immunization breaks tolerance in a hepatitis C virus transgenic mouse
      model.
AB  - Chronic hepatitis C infection (HCV) is associated with high morbidity and
      mortality due to limited treatment options. HCV transgenic mice can be used as
      surrogate model of chronic HCV infection and may therefore be a small animal
      model for the evaluation of therapeutic vaccination strategies. We immunized
      transgenic mice expressing HCV structural proteins with an HCV core and a mouse
      IL-2 expression plasmid to study the cellular and humoral immune responses. DNA
      based immunization induced a significant CD4+ T cell proliferative response and a
      CD8+ cytotoxic T cell response. Only low amounts of anti-HCV core antibodies were
      detected after genetic immunization. No liver damage was observed in the liver of
      immunized mice despite low level HCV core transgene expression and the presence
      of peripheral cellular immunity. These results demonstrate that DNA-based
      immunization may result in activation of previously tolerant T cells and is
      therefore a promising approach for treatment of chronic HCV infection.

PMID- 17012869
TI  - The prospect of vaccination to prevent type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which genes and environment
      contribute to cell-mediated immune destruction of insulin-producing beta cells in
      the pancreatic islets. Primary prevention by traditional 'positive' vaccination
      awaits evidence that infectious agents trigger T1D. The pre-clinical phase of
      T1D, in which at-risk individuals can be infected by the presence of
      autoantibodies to islet antigens, is a window for secondary prevention. The Holy
      Grail of therapy is 'negative' vaccination to induce immune tolerance against
      disease-specific autoantigens that drive immune-mediated pathology. This can be
      achieved by administering autoantigen via a 'tolergenic' (e.g., muscosal,
      intradermal) route, cell (e.g., resting dendritic cell), mode (e.g., with
      blockade of c0-stimulation molecules) or form (as an 'altered peptide ligand').
      Although effective in rodent models of autoimmune disease, these strategies have
      so far been disappointing in humans. This review discusses the prospects of
      vaccination to prevent T1D, focusing on autoantigen-specific mucosal tolerance.

PMID- 17012870
TI  - Lot-to-lot consistency of a combined hexavalent diptheria-tetanus-acellular
      pertussis, hepatitis B, Inactivated polio and haemophilus B conjugate vaccine,
      administered to healthy chilean infants at two, four and six months of age.
AB  - OBJECTIVES: To assess the safety, immunogenicity and lot consistency of a liquid
      hexavalent combined vaccine (DTaP-IPV-PRP approximately T-HBs, HEXAVAC) (Sanofi
      Pasteur MSD, France) administered to infants at two, four and six months of age.
      METHODS: A total of 1028 infants were vaccinated with one of three vaccine lots,
      in a randomized, double-blind fashion. Equivalence testing was used to compare
      post-vaccination seroprotection/seroconversion rates and geometric mean titers
      (GMTs) for each antigen between the three lots. Blood samples were drawn before
      vaccination and one month after the third dose. Local and systemic adverse events
      were monitored for three days following each injection. RESULTS: Equivalence
      between lots was demonstrated for all antigens, on post-dose 3
      seroprotection/seroconversion rates and GMTs. Reported rates of local and
      systemic adverse events tended to increase with subsequent doses. Altogether,
      11.8% of the infants reported at least one adverse local event (mainly redness
      and induration/swelling) after the first dose and 36.1% after the third dose.
      Systemic adverse events (mainly irritability and fever) were reported by 39.2% of
      the infants after the first dose and by 57.5% after the third one. CONCLUSION:
      Three separate lots of the liquid hexavalent combined vaccine induced
      consistently protective antibody responses against all antigens. These results
      and the well established clinical tolerability of this combined vaccine make it
      suitable for primary immunization of infants at two, four and six months of age.

PMID- 17012871
TI  - Safety and immunogenicity of two formulations of a hexavalent diphtheria-tetanus
      acellular pertussis-inactivated poliovirus-Haemophilus influenzae conjugate
      hepatitis B vaccine in 15 to 18-month-old children.
AB  - Combination vaccines decrease the number of injections and improve parental
      satisfaction and vaccination schedule compliance. In a phase 1, randomized,
      partially-blinded, single-dose booster study, we evaluated two formulations of an
      investigational liquid hexavalent vaccine containing diphtheria, tetanus,
      acellular pertussis (5-component), inactivated poliovirus, Haemophilus influenzae
      b conjugate and hepatitis B surface antigen (DTaP-IPV-Hib-HBV) in 60 healthy
      toddlers, 15 to 18 months of age, who had been primed with three doses of a
      licensed pentavalent diphtheria, tetanus, acellular pertussis (5-component),
      inactivated poliovirus, Haemophilus influenzae b conjugate (DTaP-IPV//PRP-T)
      vaccine. The DTaP-IPV//PRP-T vaccine was used as a control in 30 subjects. The
      investigational formulations, which contained the same DTaP-IPV components,
      differed only in Hib (content and conjugate) and HBV (content) (PRP-T/HBV10 = 12
      mug Hib tetanus toxoid conjugate with 10 microg HBsAg; PRP-OMPC/HBV15 = 6 microg
      Hib Neisseria meningitidis outer membrane protein complex with 15 microg HBsAg).
      Injection-site pain, redness and swelling were reported by 46.7%, 46.7%, and
      20.0% of the licensed vaccine recipients, 43.3%, 43.3%, and 26.7% of PRP-T/HBV10
      recipients and 70.0%, 46.7%, and 46.7% of PRP-OMPC/HBV15 recipients,
      respectively. Fever > or = 37.8 degrees C and irritability were reported by 0%
      and 16.7% of licensed vaccine recipients, 10.3% and 23.3% of PRP-T/HBV10
      recipients and 30.0% and 16.7% of PRP-OMPC/HBV15 recipients, respectively. There
      were no apparent differences between the groups in the proportion of participants
      achieving predefined, threshold or seroprotective immune responses. Geometric
      mean antibody levels for all antigens were similar except for anti-PRP levels,
      which were 19.0 microg/mL in recipients of the licensed vaccine, 40.8 microg/mL
      in PRP-T/HBV10 recipients and 9.4 microg/mL in PRP-OMPC/HBV15 recipients. We
      conclude that the hexavalent formulations appear generally well tolerated and
      immunogenic as a booster dose in these toddlers.

PMID- 17012872
TI  - Group C meningococcal polysaccharide-tetanus toxoid conjugate vaccine: a meta
      analysis of immunogenicity, safety and posology.
AB  - A conjugate vaccine comprised of de-O-acetylated group C meningococcal
      polysaccharide coupled to tetanus toxoid (GCMP-TT) has been licensed in 32
      countries and incorporated in a comprehensive UK vaccination program. Extensive
      evidence, forming the subject of this meta-analysis, has rapidly accumulated on
      the immunogenicity, safety and posology of GCMP-TT as well as its epidemiological
      impact. GCMP-TT has been shown effective after a single dose in individuals >12
      months of age, and initial posology specified three doses in infants. However,
      based on a recent clinical trial, posology was reduced to two doses in infants.
      Pooled protection rate, defined as proportion of subjects with serum bactericidal
      antibody (SBA) levels > or = 1:8, was 99.4% (CI, 98.2-99.9%) in seven clinical
      trials covering all age groups. Robust responses to GCMP-TT have been
      demonstrated with respect to SBA, IgG levels and antibody avidity. In post
      marketing pharmacosurveillance encompassing >12 x 10(6) GCMP-TT doses distributed
      worldwide, the vaccine has been well tolerated with an incidence rate of 0.01%
      for all the most commonly encountered types of adverse events. After a catch-up
      UK vaccination campaign where 5-8 year old children were primarily given GCMP-TT,
      a 93% decline in meningococcal disease incidence was observed. In view of its
      immunogenicity, safety and potential suitability for use among infants in reduced
      dose schedules, GCMP-TT appears to mark a major advance over predecessor
      polysaccharide vaccines for the prevention of meningococcal C disease.

PMID- 17012873
TI  - Live attenuated chimeric yellow fever dengue type 2 (ChimeriVax-DEN2) vaccine:
      Phase I clinical trial for safety and immunogenicity: effect of yellow fever pre
      immunity in induction of cross neutralizing antibody responses to all 4 dengue
      serotypes.
AB  - A randomized double-blind Phase I Trial was conducted to evaluate safety,
      tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera
      (ChimeriVax-DEN2) in comparison to that of YF vaccine (YF-VAX). Forty-two healthy
      YF naive adults randomly received a single dose of either ChimeriVax-DEN2 (high
      dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX by the
      subcutaneous route (SC). To determine the effect of YF preimmunity on the
      ChimeriVax-DEN2 vaccine, 14 subjects previously vaccinated against YF received a
      high dose of ChimeriVax-DEN2 as an open-label vaccine. Most adverse events were
      similar to YF-VAX and of mild to moderate intensity, with no serious side
      effects. One hundred percent and 92.3% of YF naive subjects inoculated with 5.0
      and 3.0 log10 PFU of ChimeriVax-DEN2, respectively, seroconverted to wt DEN2
      (strain 16681); 92% of subjects inoculated with YF-VAX seroconverted to YF 17D
      virus but none of YF naive subjects inoculated with ChimeriVax-DEN2 seroconverted
      to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and
      4 were observed in YF naive subjects inoculated with either ChimeriVax-DEN2 or YF
      VAX. In contrast, 100% of YF immune subjects inoculated with ChimeriVax-DEN2
      seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing
      antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1
      year. These data demonstrated that (1) the safety and immunogenicity profile of
      the ChimeriVax-DEN2 vaccine is consistent with that of YF-VAX, and (2)
      preimmunity to YF virus does not interfere with ChimeriVax-DEN2 immunization, but
      induces a long lasting and cross neutralizing antibody response to all 4 DEN
      serotypes. The latter observation can have practical implications toward
      development of a dengue vaccine.

PMID- 17012875
TI  - The live attenuated dengue serotype 1 vaccine rDEN1Delta30 is safe and highly
      immunogenic in healthy adult volunteers.
AB  - BACKGROUND: The live attenuated DEN1 vaccine candidate virus rDEN1Delta30 has
      been evaluated in preclinical animal models and found to be attenuated and
      immunogenic. These promising preclinical studies have identified rDEN1Delta30 as
      a candidate DEN1 vaccine virus for further testing in a human Phase I clinical
      trial. METHODS: rDEN1Delta30 at a dose of 10(3) pfu was administered as a single
      inoculation to twenty healthy adult volunteers. Eight additional volunteers
      received placebo. Volunteers were monitored closely for adverse events and serum
      was collected on study days 0, 28, 42 and 180 for determination of neutralizing
      antibody titer. RESULTS: The vaccine was well tolerated by the vaccinees. The
      most common adverse events observed were a transient asymptomatic rash in 40% of
      vaccinees and a mild neutropenia in 45% of vaccinees. No vaccinee developed a
      dengue-like illness. The vaccine was highly infectious and immunogenic with 95%
      of vaccinees developing a > or =4-fold rise in serum neutralizing antibody titer
      against DEN1 that persisted throughout the six month duration of the trial.
      CONCLUSIONS: The rDEN1Delta30 vaccine is safe and induced a potent and durable
      antibody response against DEN1. It is a promising vaccine candidate for inclusion
      in a tetravalent dengue vaccine formulation.

PMID- 17012876
TI  - Correlation between mouse potency and in vitro relative potency for human
      papillomavirus Type 16 virus-like particles and Gardasil vaccine samples.
AB  - An in vitro relative potency (IVRP) assay has been developed as an alternative to
      the mouse potency assay used to release Merck's human papillomavirus (HPV)
      vaccine, Gardasil, for early phase clinical trials. The mouse potency assay is a
      classical, in vivo assay, which requires 4-6 weeks to complete and exhibits
      variability on the order of 40% relative standard deviation (RSD). The IVRP assay
      is a sandwich-type immunoassay that is used to measure relative antigenicity of
      the vaccine product. The IVRP assay can be completed in three days, has a
      variability of approximately 10% RSD and does not require the sacrifice of live
      animals. Because antigen detection is achieved using H16.V5, a neutralizing
      monoclonal antibody, which binds to a clinically-relevant epitope, the relative
      antigenicity measured by the IVRP assay is believed to be a good predictor of in
      vivo potency. In this study, the relationship between immunogenicity, as measured
      by the mouse potency assay and antigenicity as measured by the IVRP assay, is
      demonstrated. Freshly manufactured and aged samples produced using two different
      manufacturing processes were tested using both methods. The results demonstrate
      that there is an inverse correlation between the IVRP and mouse potency assays.
      Additionally, clinical results indicate IVRP is predictive of human
      immunogenicity. Thus, antigenicity, as defined by the H16.V5 epitope, can be used
      as a surrogate for immunogenicity and the IVRP assay is suitable for use as the
      sole potency test for Gardasil samples.

PMID- 17012877
TI  - Development of an approach for the laboratory toxicological evaluation of
      Bordetella pertussis adenylate cyclase genetic toxoid constructs as multipurpose
      vaccines.
AB  - Detoxified recombinant CyaA constructs have been developed as potential viral and
      tumoral epitope carriers for immunoprophylactic and therapeutic vaccination and
      as antigen candidates for inclusion in acellular pertussis vaccines. In this
      work, we attempt to explore a test system for the laboratory safety evaluation of
      CyaA preparations. Endotoxin was determined in vitro by the Limulus amoebocyte
      lysate assay. Cytotoxicity was measured by a tetrazolium salt test and a lactate
      dehydrogenase release assay using murine and human phagocytic cell lines. Cell
      viability was < 50% at concentrations > 1 microg/mL of the wild type toxin and
      concentrations in the nanogram range inhibited the zymosan-induced oxidative
      burst as measured by chemiluminescence. However, no effects were observed for
      detoxified and non-acylated forms of CyaA at comparable and higher toxin
      concentrations. Effects found in the in vitro assays could not be related to the
      in vivo mouse weight gain test used as a general toxicity test. In vitro
      cytotoxicity and oxidative burst studies on phagocytes, and the evaluation of
      endotoxin levels are useful for safety screening of CyaA constructs. However, in
      vivo specific toxicity tests and potential toxic implications of enzymatic
      activity-independent effects of CyaA on cell function should be investigated.

PMID- 17012878
TI  - Safety and immunogenicity of a meningococcal (Groups A, C, Y, W-135)
      polysaccharide diphtheria toxoid conjugate vaccine in healthy children aged 2 to
      10 years in Chile.
AB  - Immune responses to meningococcal conjugate (Menactra; MCV-4) and plain
      polysaccharide (Menomune-A/C/Y/W-135; PSV-4) vaccines against serogroups A, C, Y,
      and W-135 were assessed in 220 of 1037 Chilean children aged 2 to 10 years
      participating in a comparative safety trial. Both vaccines were generally well
      tolerated. Geometric mean serum bactericidal antibody (SBA) titers 28 days
      postvaccination were comparable in both groups for all four serogroups.
      Seroconversion was evident in > 97% of MCV-4 and > 90% of PSV-4 vaccinees who
      tested seronegative at baseline. Menactra safely induced broad and robust immune
      responses against serogroups A, C, Y and W-135 in this population.

PMID- 17012879
TI  - Investigation in a model system of the effects of combinations of anthrax and
      pertussis vaccines administered to service personnel in the 1991 Gulf War.
AB  - The toxicity and immunogenicity of the anthrax and pertussis vaccine combinations
      used in the 1991 Gulf War was assessed in NIH, A/J and Balb/c mice. Inoculation
      of pertussis vaccines, vaccine combinations, or aluminium salt caused illness,
      splenomegaly and significant weight loss. Although some animals recovered
      eventually, a lethal form of ascites developed in some NIH mice and body weights
      of A/J and Balb/c mice remained below normal levels. Inoculation of anthrax
      vaccine produced little effect. Exposure to diluted vaccine combinations produced
      less serious side effects of shorter duration. Single vaccinations induced
      specific IgG1 antibodies whereas a mixture of IgG1 and IgG2a was produced after
      multiple injections. Antigen stimulation of spleen cells from mice exposed to
      pertussis vaccines induced high levels of NO and IL-6, whereas stimulated spleen
      cells from mice exposed to anthrax vaccine produced only low levels of IL-6. In
      mice, pertussis vaccines act as an adjuvant for anthrax vaccine, but these
      vaccines are also the major cause of toxicity of the vaccine combination. The
      relatively high vaccine dose used, together with the low sensitivity of mice to
      anthrax toxin, emphasises that caution should be exercised in applying these
      results to human recipients of these vaccines.

PMID- 17012880
TI  - Association between immunogenicity and adsorption of a recombinant Streptococcus
      pneumoniae vaccine antigen by an aluminum adjuvant.
AB  - The impact on immunogenicity of the degree of adsorption of three Streptococcus
      pneumoniae (Sp) vaccine antigens to aluminum adjuvants was studied. The three
      antigens evaluated (Sp1, Sp2 and Sp3) were highly adsorbed by aluminum hydroxide
      adjuvant, but not adsorbed by aluminum phosphate adjuvant. All of the Sp antigens
      adjuvanted with aluminum hydroxide elicited higher antibody responses in mice
      than formulations prepared with aluminum phosphate or non-adjuvanted antigen.
      Varying the percent aluminum-bound Sp antigen in the formulated vaccine affected
      the observed antibody responses. These observations suggest that the antibody
      response observed for Sp antigens in this study is stimulated by a depot effect
      of the antigen bound to an aluminum adjuvant.

PMID- 17012881
TI  - Hospitalization by pneumonia and influenza in the 50-64 year old population in
      Spain (1999-2002).
AB  - This epidemiological survey was undertaken to estimate the burden of hospital
      admissions for pneumonia and influenza in 50-64 years old persons in Spain during
      a four-year period (1999-2002). Data were obtained from the national surveillance
      system for hospital data maintained by the Ministry of Health and covering more
      than 95% of Spanish hospitals. There were 35,620 hospital admissions for
      pneumonia and influenza (ICD 9 CM 480-487; first listed diagnosis) during the
      study period. Annual incidence was 143 cases per 100,000 population. Rate of
      death and case-fatality rate were 8 per 100,000 population and 5.6%,
      respectively. The average length of hospitalization was 10.4 days. Men and older
      age groups showed a higher incidence, rate of death and case-fatality rate. These
      hospitalizations of 50-64 years old persons impose an annual direct cost of 12 to
      24 millions euros. Preventive measures, such as vaccination will reduce pneumonia
      related morbidity and could result in large cost savings to the Health Care
      System.

PMID- 17012882
TI  - Safety and immunogenicity of a pentavalent combination vaccine (diphtheria,
      tetanus, acellular pertussis, polio, and haemophilus influenzae type B conjugate)
      when administered as a fourth dose at 15 to 18 months of age.
AB  - A DTaP-IPV//PRP-T combination vaccine (Pentacel) has been universally used in
      Canada to provide immunization against diphtheria, tetanus, pertussis, polio, and
      Haemophilus influenzae type b with single injections at 2, 4, 6 and 18 months of
      age. This randomized, multicenter study was conducted to evaluate administration
      of a fourth dose of DTaP-IPV//PRP-T at 15 to 18 months of age, similar to the US
      immunization schedule. Participants who had received three doses of DTaP-IPV//PRP
      T by 8 months of age were enrolled at 12 months and randomized to receive a
      fourth dose at 15, 16, 17 or 18 months. Antibody levels for each vaccine antigen
      were measured prior to and four weeks following booster vaccination. Overall,
      1782 subjects were immunized and monitored for adverse events, and 735 were
      evaluated for immune responses. Preimmunization antibody levels differed
      minimally by age, for all antigens. The immune responses elicited by DTaP
      IPV//PRP-T were comparable between participants vaccinated at 15 or 16 months and
      those vaccinated at 17 or 18 months, as demonstrated by specific antibody
      geometric mean titers, seroprotection/seroresponse rates, and reverse cumulative
      distribution curves. The fourth dose was well tolerated in all age groups.
      Toddlers at 15, 16, 17 or 18 months of age are equally suitable recipients for
      booster immunization with the DTaP-IPV//PRP-T vaccine.

PMID- 17012883
TI  - Rapid licensure of a new, inactivated influenza vaccine in the United States.
AB  - BACKGROUND: The unexpected problems at 1 of 2 US licensed manufacturers of
      trivalent inactivated influenza virus vaccine (TIV) in 2004 highlights the urgent
      need for additional vaccine sources. We evaluated a split virus TIV (Fluarix,
      GSK), to generate data supportive of a license application in the US. METHODS:
      Healthy adults ages 18-64 years at four centers were randomly assigned to receive
      a single IM injection of Fluarix (n = 763) or placebo (n = 193) in double-blind
      fashion. Subjects were monitored for safety and serum hemagglutination-inhibition
      (HAI) titers determined before and 21 days after vaccination. RESULTS: Vaccine
      was well tolerated, with only mild to moderate myalgias and injection site pain
      and redness being more common in vaccine than placebo recipients. Four-fold or
      greater increases in serum HAI titers were seen in 60%, 62% and 78% of vaccine
      recipients against the H1, H3, and B components of the vaccine, respectively, and
      post-vaccination titers of > 1:40 achieved in 98%, 99% and 99% of subjects,
      exceeding the prespecified criteria for acceptability for all three antigens.
      CONCLUSIONS: Fluarix has a safety and immunogenicity profile like other US
      licensed inactivated influenza vaccines and should be effective when used to
      immunize US adults. SUMMARY LINE: The results of this study were pivotal for the
      rapid approval of Fluarix in the US for use in adults 18 years of age or older.

PMID- 17012884
TI  - Rotavirus vaccines: round two.

PMID- 17012885
TI  - Active specific immunotherapy with autologous tumor cell vaccines for stage II
      colon cancer: logistics, efficacy, safety and immunological Pharmacodynamics.
AB  - In the area of cancer treatment, immunotherapy with vaccines has suffered in the
      last five years, due to many clinical trial failures. One must keep in mind
      however, that many of the clinical trials conducted in the past decade were
      performed without the benefit of sound regulatory guidance or validated and
      compliant manufacturing processes. This has clearly been the case for patient
      specific, tumor cell vaccine therapy. The safety concerns that emanated within
      the regulatory agencies from the Somatic Cell Therapy concepts, translated to
      active specific immunotherapy with vaccines. Fortunately, in the past five years
      advances in understanding the immune system, improved design of clinical trials,
      improvement and compliance of manufacturing processes provided opportunities to
      significantly improve efficacy and safety. Clearly, the vaccine research
      establishment has learned the importance of not just selecting antigens but the
      requirement of tumor associated immunogens that can stimulate a functional immune
      response. Also, it has become clear that immunotherapy works best in situations
      of minimal residual disease. Finally, more realistic endpoints in clinical trials
      have been recognized and accepted by oversight review committees. This commentary
      describes the "trials and tribulations" of developing a patient specific,
      autologous tumor cell vaccine for therapy of Stage II colon cancer.

PMID- 17012886
TI  - Preclinical and clinical safety studies on DNA vaccines.
AB  - DNA vaccines are based on the transfer of genetic material, encoding an antigen,
      to the cells of the vaccine recipient. Despite high expectations of DNA vaccines
      as a result of promising preclinical data their clinical utility remains
      unproven. However, much data is gathered in preclinical and clinical studies
      about the safety of DNA vaccines. Here we review current knowledge about the
      safety of DNA vaccines. Safety concerns of DNA vaccines relate to genetic,
      immunologic, toxic, and environmental effects. In this review we provide an
      overview of findings related to the safety of DNA vaccines, obtained so far. We
      conclude that the potential risks of DNA vaccines are minimal. However, their
      safety issues may differ case-by-case, and they should be treated accordingly.

PMID- 17012887
TI  - Influenza vaccination and risk of incident myocardial infarction.
AB  - BACKGROUND: Several studies suggest that influenza vaccination may be associated
      with a decreased risk of acute cardiovascular events. We examined the association
      between influenza vaccination and risk of incident myocardial infarction (MI) in
      persons at least 65 years of age in a population-based case-control study.
      METHODS: Case subjects were members of Group Health Cooperative (GHC), a health
      maintenance organization, with incident MI during 1992-1998. Control subjects
      were GHC members without a history of MI who were frequency matched to case
      subjects by age, sex, calendar year, and presence of treated hypertension. The
      medical records of 750 case subjects with MI and 1735 controls were reviewed.
      RESULTS: Receipt of influenza vaccine was not associated with risk of incident MI
      during the months of November through March (odds ratio [OR]: 0.97, 95%
      confidence interval [CI]: 0.75-1.27) or April through September (OR: 0.97, 95% CI
      0.75-1.26). CONCLUSIONS: This study does not provide evidence supporting an
      association of influenza vaccination and reduction in risk of myocardial
      infarction.

PMID- 17012888
TI  - Modeling future changes to the meningococcal serogroup C conjugate (MCC) vaccine
      program in England and Wales.
AB  - The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully
      controlled serogroup C disease, due to high vaccine effectiveness and substantial
      herd immunity. However, children immunised at 2, 3 and 4 months of age receive
      only short-term direct protection and may be at risk of disease 15 months after
      vaccination. To investigate this we applied a mathematical model to predict the
      future epidemiology of serogroup C disease, with and without changes to the
      immunization schedule. Only a few cases of serogroup C disease were predicted to
      occur over the next few years because of persisting herd immunity, even without a
      change to the vaccine schedule. The inclusion of a booster dose is likely to
      improve the impact of the MCC program and reducing the number of doses in infancy
      will improve cost-effectiveness and create space in the schedule for the addition
      of other vaccines.

PMID- 17012889
TI  - Military hospitalizations among deployed US service members following anthrax
      vaccination, 1998-2001.
AB  - Safety concerns have confronted the Department of Defense Anthrax Vaccine
      Immunization Program since inception in 1998. To determine if anthrax vaccination
      was associated with an increased risk of hospitalization, a historical cohort
      study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken
      and analyzed with Cox proportional hazards models. The study population consisted
      of 170,723 active duty US service members who were anthrax-vaccinated and
      deployed during the time period January 1, 1998 to December 31, 2001. Study
      outcomes included hospitalizations due to any-cause, 14 broad International
      Classification of Diseases diagnostic categories, autoimmune organ specific and
      organ non-specific hospitalizations, and asthma. After adjustment, anthrax
      vaccination was associated with significantly fewer hospitalizations for any
      cause, diseases of the blood and blood forming organs, and diseases of the
      respiratory system. Comparing anthrax post-vaccination hospitalization experience
      with the pre-vaccination period resulted in no significant increased hazard for
      any of the hospitalization outcomes studied. Although there was no apparent
      increase in risk of morbidity in this study population, the relationship between
      anthrax vaccine and deployment on health outcomes among US service members needs
      further study.

PMID- 17012890
TI  - Safety and immunogenicity of a new fully liquid DTPw-HepB-Hib combination vaccine
      in infants.
AB  - We assessed the safety and immunogenicity of a fully liquid, DTPw-HepB-Hib
      combination vaccine (Quinvaxem) in comparison with separately administered DTPw
      Hib and hepatitis B vaccines. Infants participating in this open-label,
      randomized, phase II study received a primary vaccination course using a 2-3-4
      month schedule. Blood samples were taken immediately prior to the first and one
      month after the third vaccination. Adverse events were assessed over a 7-day post
      vaccination period using subject diaries. After completion of the primary
      vaccination course, 94.7% [95% CI: 89.8-97.7%] of infants receiving the
      combination vaccine achieved protective anti-HBs antibody titers (> or = 10
      mIU/mL) with a mean 39-fold increase in GMTs in comparison with 99.3% [95% CI:
      96.3-100%] seroprotection and a mean 29-fold GMT increase in the comparator
      group. Diphtheria, tetanus and Haemophilus influenzae type b (Hib) seroprotection
      rates and pertussis seroconversion rates were also similar between the two
      groups. There was no statistically significant difference in GMTs for diphtheria
      between the two groups, but significant differences were shown for tetanus, Hib,
      and pertussis with higher GMTs for each antigen observed in the comparator group.
      The combination vaccine was well tolerated, with fever (body temperature > or =
      38 degrees C) being the most frequently reported adverse event in both the DTPw
      HepB-Hib (12.5% [95% CI: 7.7-18.8%]) and comparator (12.6% [95% CI: 7.7-19.0%])
      groups. This study demonstrated that the fully liquid DTPw-HepB-Hib combination
      vaccine has safety and immunogenicity profiles similar to the DTPw-Hib and
      hepatitis B vaccines when administered separately.

PMID- 17012891
TI  - Evaluation of the thermal stability of Gardasil.
AB  - The thermostability of GARDASIL (Merck & Co., Inc, Whitehouse Station, NJ, USA),
      a developmental vaccine against human papillomavirus (HPV), was evaluated using
      an enzyme immunoassay, referred to as the in vitro relative potency (IVRP) assay
      and differential scanning calorimetry (DSC). Gardasil samples were stored at
      temperatures ranging from 4 to 42 degrees C and tested for IVRP at various time
      points. Extrapolation of the IVRP results indicates GARDASIL is extremely stable.
      The half-life of the vaccine is estimated to be 130 months or longer at
      temperatures up to 25 degrees C. At 37 degrees C, the half-life is predicted to
      be 18 months and at 42 degrees C, the half-life is predicted to be approximately
      three months. Differential scanning calorimetry (DSC) analysis was used to
      evaluate the process of protein denaturation during a rapid temperature increase
      (as opposed to long-term storage at a specific temperature). Differences were
      seen among the DSC profiles of the four HPV types tested. This indicates that
      small differences in the amino acid structure can have a significant effect on
      the intermolecular contacts that stabilize the L1 proteins and the VLP assembly.
      For the Gardasil samples evaluated here, DSC results demonstrated the relative
      overall structural stability of the VLPs, but were not predictive of the
      excellent long-term stability observed with the IVRP assay.

PMID- 17012892
TI  - Maturation of recombinant hepatitis B virus surface antigen particles.
AB  - The major surface antigen of Hepatitis B virus (HBsAg) is a cysteine-rich, lipid
      bound protein with 226 amino acids. Recombinant HBsAg (rHBsAg) with associated
      lipids can self-assemble into 22-nm immunogenic spherical particles, which are
      used in licensed Hepatitis B vaccines. Little is known about the structural
      evolvement or maturation upon assembly beyond an elevated level of disulfide
      formation. In this paper, we further characterized the maturation of HBsAg
      particles with respect to their degree of cross-linking, morphological changes,
      and changes in conformational flexibility. The lipid-containing rHBsAg particles
      undergo KSCN- and heat-induced maturation by formation of additional intra- and
      inter-molecular disulfide bonds. Direct measurements with atomic force microscopy
      (AFM) revealed morphological changes upon maturation through KSCN-induced and
      heat-/storage-incurred oxidative refolding. Particle uniformity and regularity
      was greatly improved, and protrusions formed by the protein subunits were more
      prominent on the surface of the mature particles. Decreased conformational
      flexibility in the mature rHBsAg particles was demonstrated by millisecond-scale
      unfolding kinetics in the presence of an environment-sensitive conformation
      probe. Both the accessible hydrophobic cavities under native conditions and the
      changeable hydrophobic cavities upon denaturant-induced unfolding showed
      substantial decrease upon maturation of the rHBsAg particles. These changes in
      the structural properties may be critical for the antigenicity and immuno
      genicity of this widely-used vaccine component.

PMID- 17012893
TI  - Determinants of pneumococcal vaccination among patients with chronic obstructive
      pulmonary disease in Spain.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of
      morbidity and mortality in adults. Pneumococcal vaccination is recommended to
      persons suffering COPD. This study aimed at describing pneumococcal vaccination
      coverages in patients with COPD and analyzing the factors associated with such
      vaccination. METHODS: This was designed as a descriptive study conducted in the
      primary-care setting. Each of the 2422 medical practitioners included in the
      study had to enroll five COPD patients. As the dependent variable, we took the
      answer to the question, "Have you ever been given a pneumococcal vaccine shot at
      some time in your life?". As independent variables, we analyzed sociodemographic,
      health-status and lifestyle variables, along with history of influenza
      vaccination. RESULTS: A total of 10,711 patients were enrolled and, 32.5% (95% CI
      31.6-33.4) of participants reported receiving pneumococcal vaccination. Female
      gender, higher age and more advanced COPD stage were the variables associated
      with a higher likelihood of being vaccinated. History of influenza vaccination in
      the most recent campaign was also associated with pneumococcal vaccination.
      CONCLUSION: Pneumococcal vaccination coverages among Spanish COPD patients are
      low and strategies to improve them must be implemented as a matter of urgency.

PMID- 17012894
TI  - Defining the role of vascular smooth muscle cell apoptosis in atherosclerosis.
AB  - Vascular smooth muscle cell (VSMC) apoptosis occurs in many arterial diseases,
      including aneurysm formation, angioplasty restenosis and atherosclerosis.
      Although VSMC apoptosis promotes vessel remodelling, coagulation and
      inflammation, its precise contribution to these diseases is unknown, given that
      apoptosis frequently accompanies vessel injury or alterations to flow. Using
      transgenic mice with selective induction of VSMC apoptosis, a recent study has
      precisely determined the direct consequences of VSMC apoptosis in both normal
      vessels and atherosclerotic plaques. Surprisingly, normal arteries can withstand
      huge cell losses with little change in active or passive properties. Normal
      vessels demonstrate highly efficient clearance of apoptotic bodies, even in the
      absence of professional phagocytes. In contrast, VSMC apoptosis alone is
      sufficient to induce multiple features of vulnerability to rupture in plaques,
      identifying VSMC apoptosis as a critical process determining plaque stability.

PMID- 17012895
TI  - Applications of influenza virosomes as a delivery system.
AB  - The induction of effective cellular and humoral immune responses against antigens
      is the major goal in vaccination strategies against infectious diseases and
      cancer. In this review, we will discuss influenza virosomes as a versatile
      delivery system for molecules of a different nature, such as proteins, peptides
      and nucleic acids. These molecules can be administered in different ways, such as
      nasal, muscular or dermal routes, also facilitating the uptake of the antigen by
      antigen-presenting cells (APC) and inducing a specific humoral and cell-mediated
      immune response, particularly a CTL response. Influenza virosomes, due to their
      applicability in different medical fields, are a promising tool in vaccinology
      and immunotherapy applications.

PMID- 17012896
TI  - Immunogenicity and reactogenicity to Haemophilus influenzae type B (Hib)
      conjugate vaccine among rural Alaska adults.
AB  - BACKGROUND: Despite routine vaccination and declining disease rates, Haemophilus
      influenzae type b (Hib) invasive disease still occurs in rural Alaska.
      Colonization studies indicate persistent transmission of Hib among village
      residents, including adults. As part of a project to eliminate Hib carriage in
      three rural villages, we evaluated a cohort of Alaska adults for antibody
      response and reactogenicity to a single dose of Hib conjugate vaccine (HbOC).
      METHODS: 75 previously unvaccinated, randomly-selected adults in one village
      received a single dose of HbOC vaccine and completed a side-effects diary. Sera
      and oropharyngeal specimens were collected at baseline, two months and one year.
      RESULTS: No participants were colonized with Hib or reported serious side
      effects. At baseline, 97% of adults had IgG anti-PRP concentrations > or = 0.15
      microg/mL, 69% > or = 1 microg/mL, and 28% > or = 5 microg/mL. Two months post
      vaccination, 100% of participants had concentrations > or = 0.15 microg/mL, 93% >
      or = 1 microg/mL, and 86% > or = 5 microg/mL. After 1 year, 98% had IgG anti-PRP
      concentrations > or = 0.15 microg/mL, 86% > or = 1 microg/mL, and 67% > or = 5
      microg/mL. GMCs were 1.9, 33.3 and 8.4 microg/mL at baseline, 2 months and 1 year
      post-vaccine, respectively (p < 0.01). Serum bactericidal activity increased from
      a baseline geometric mean titer of 2,205 to 8,349 two months post vaccination and
      declined to 1102 after one year. CONCLUSIONS: HbOC vaccine was immunogenic and
      well-tolerated among Alaskan adults. Nearly 90% of the adults developed an
      antibody level associated with protection against Hib colonization which
      persisted for 1 year in 67% of participants.

PMID- 17012897
TI  - Dose-response relationship of DNA and recombinant fowlpox virus prime-boost HIV
      vaccines: implications for future trials.
AB  - Estimating effective doses of novel HIV vaccines is challenging. Dose-response
      analyses of DNA and fowlpox virus HIV vaccines showed that 1 mg of DNA vaccine
      and 5 x 10(7)pfu of fowlpox virus booster was immunogenic in macaques. However,
      this dose was poorly immunogenic in humans. When adjusted for body surface area,
      the human dose studied was equivalent to a poorly immunogenic lower dose in
      monkeys. These data provide a rationale for guiding dosing in future trials of
      HIV vaccine technologies.

PMID- 17012898
TI  - Vaccine development for an imminent pandemic: why we should worry, what we must
      do.
AB  - The avian H5N1 virus continues to evolve and poses an imminent pandemic threat.
      Pandemic vaccine development, however, has progressed slowly. For it to succeed,
      it must be based on a public health perspective that reflects the arithmetic of
      pandemic vaccine demand, especially by countries without vaccine companies.
      Clinical trials of H5N1 vaccines have been discouraging, and we must understand
      why the H5N1 virus is so poorly immunogenic. Antigen-sparing pandemic vaccines
      will be required, and future trials must identify the most effective adjuvant and
      determine whether whole virus vaccines will be needed. Problems related to
      intellectual property and concerns about several regulatory issues must be
      resolved. Public funding for clinical trials must be provided and firm leadership
      and coordination exercised by national and international (WHO) public health
      officials. Vaccination for an imminent pandemic requires a global perspective not
      only for vaccine development but also for vaccine production and distribution.

PMID- 17012899
TI  - States' emergency orders regarding the 2004-05 influenza vaccine shortage.
AB  - Influenza vaccine shortages during the 2004-05 season led some states to issue
      emergency orders that prioritized high-risk groups and in some cases threatened
      criminal penalties. Decision-making that led states to issue - or not issue -
      these orders has not been examined. Therefore, we conducted analyses of semi
      structured, in-depth interviews with health officials in 23 states, in order to
      identify principal decision-making factors and patterns regarding emergency flu
      vaccine orders. Four of 14 issuing states and one of 9 non-issuing states had a
      formal structure for decisions of this nature; 3 states utilized a bioterrorism
      preparedness infrastructure. Eight issuing states cited inadequate or uncertain
      supply as most important in their decision-making. Four issuing states said that
      informing the public that high-risk prioritization was a state decision (and not
      a provider-specific decision) was most important. Among non-issuing states, 7/9
      believed they could accomplish their objectives without issuing an order. No
      states had formal mechanisms to assess vaccine supply or monitor physicians'
      adherence to prioritization guidelines. We conclude that broad differences in
      states' approaches to influenza vaccine supply illustrate 3 salient themes:
      decentralization of vaccine supply control and management, lack of monitoring and
      enforcement capacity, and benefits of disaster preparedness efforts.

PMID- 17012900
TI  - A pilot study of SRL 172 (killed Mycobacterium vaccae) in healthy chronic
      hepatitis B carriers and hepatitis B vaccine non-responders.
AB  - OBJECTIVE: To assess possible development of immunity to HBV by the use of
      hepatitis B vaccine in combination with the adjuvant M. vaccae (SRL 172) in
      healthy chronic HBsAg carriers and in healthy non-responders to hepatitis B
      vaccine. HYPOTHESIS: To utilise the known immuno-stimulatory effects of SRL 172
      (heat-killed M. vaccae) on chronic carriers of HBV and non-responders to
      hepatitis B vaccine to overcome the respective 'immune-tolerance' and 'immune
      blindness' observed in these conditions and develop immunity to hepatitis B.
      METHOD: 35 suitable healthy HBsAg carriers were randomised to receive hepatitis B
      vaccine together with either placebo or SRL172 by the intradermal route on one
      occasion. 23 HB vaccine non-responders were randomised in the same way, and
      similarly given vaccine with either SRL 172 or placebo. The HBsAg carrier
      subjects were followed-up for 12 months to monitor changes in HBV markers, anti
      HBs, clinical chemistry, immunological and clinical status. The HB vaccine non
      responders were reassessed for the development of anti-HBs at three months post
      immunisation. RESULTS: This pilot study provided evidence that SRL172 was
      moderately well tolerated and safe. One HB vaccine/placebo recipient (with
      initial prevaccination high HBV load) became HBV DNA negative and remained so for
      the 12-month duration of the study. Vaccine plus SRL172 helped induce measurably
      higher anti-HBs titres in HB vaccine nonresponders, however, because of
      relatively small participant numbers, statistically significant results were not
      obtained. CONCLUSION: Based on the development of anti-HBs in non-responders, the
      non-proprietary mixing of vaccine with SRL172 does not destroy immunogenicity of
      the vaccine and thus provides an opportunity to conduct further studies of this
      combination in hepatitis B vaccine non-responders. HB vaccine plus SRL 172 when
      given on one occasion is ineffective in treating HBsAg carriers. Interesting
      differences between the treatment groups were observed in HB viral load responses
      at 3 months post-vaccination. Consideration should be given to further studies
      using multi-dose regimens.

PMID- 17012901
TI  - Tuberculin purified protein derivative (PPD) immunoassay as an in vitro
      alternative assay for identity and confirmation of potency.
AB  - Tuberculin purified protein derivative (PPD) currently can only be standardised
      by delayed hypersensitivity skin reactions in sensitised guinea pigs. An in vitro
      dot blot immunoassay was developed for both identity and confirmation of potency
      estimation of PPD. Polyclonal antibodies (mainly IgG) were generated and
      immunoreacted with human, bovine and, to lesser extent, avian PPD preparations.
      Combining size exclusion chromatography (FPLC-SEC) and dot blot immunoassay, the
      results showed that PPD preparations were mixtures of very heterogeneous
      tuberculoproteins ranging in size from very large aggregates to very small
      degraded molecules. All individual fractions of PPD separated by size were
      immunoreactive, although those of the largest molecular sizes appeared the most
      immunoreactive in this in vitro dot blot immunoassay. This method is very
      sensitive and specific to tuberculoproteins and can be an in vitro alternative
      for the in vivo intradermal skin assay which uses guinea pigs for identity of PPD
      preparations. Although the capacity of PPD to elicit cell-mediated immune
      responses on intradermal testing has to be confirmed by in vivo assay, the dot
      blot immunoassay offers a rapid, sensitive and animal-free alternative to in vivo
      testing for confirming the identity of PPD preparations with appropriate
      potencies. This alternative assay would be particularly useful for national
      regulatory laboratories for confirming the data of manufacturers and thus
      reducing the use of animals.

PMID- 17012903
TI  - Confirmation of immunogenic consensus sequence HIV-1 T-cell epitopes in Bamako,
      Mali and Providence, Rhode Island.
AB  - The design of epitope-driven vaccines for HIV has been significantly hampered by
      concerns about conservation of vaccine epitopes across clades of HIV. In previous
      work, we have described a computer-driven method for a cross-clade HIV vaccine
      comprised of overlapping, highly conserved helper T-cell epitopes or "immunogenic
      consensus sequence epitopes" (ICS epitopes). Here, we evaluated and compared the
      immunogenicity of 20 ICS HIV epitopes in ELISpot assays performed using
      peripheral blood monocytes (PBMC) from HIV-infected donors in Providence, Rhode
      Island, USA and in Bamako, Mali, West Africa. Each core 9-mer HIV sequence
      contained in a given consensus peptide was conserved in at least 105 to as many
      as 2,250 individual HIV-1 strains. Nineteen of the 20 ICS epitopes (95%) were
      confirmed in ELISpot assays using PBMC obtained from 13 healthy, HIV-1 infected
      subjects in Providence, and thirteen of the epitopes (65%) were confirmed in
      ELISpot assays using PBMC derived from 42 discarded blood units obtained at the
      Central Blood Bank in Bamako. Twelve of the epitopes were confirmed in ELISpot
      assays performed both in Providence and Bamako. These data confirm the utility of
      bioinformatics tools to select and design novel vaccines containing "immunogenic
      consensus sequence" T-cell epitopes for a globally relevant vaccine against HIV;
      a similar approach may also be useful for any pathogen that exhibits high
      variability (influenza, HCV, or variola for example). An HIV vaccine containing
      these immunogenic consensus sequences is currently under development.

PMID- 17012902
TI  - Preclinical laboratory evaluation of a bivalent Staphylococcus aureus saccharide
      exotoxin A protein conjugate vaccine.
AB  - A bivalent, unadjuvanted conjugate vaccine composed of Staphylococcus aureus
      capsular polysaccharides type 5 and 8 (T5 and T8 PS) conjugated to a novel
      carrier protein, the mutant nontoxic recombinant Pseudomonas aeruginosa exotoxin
      A (rEPA), has been the subject of recent clinical trials. A program of
      preclinical laboratory evaluation was carried out in support of the clinical
      trials conducted by the National Vaccine Evaluation Consortium. This involved
      physical chemical characterization and limited assessment of toxicity and
      immunogenicity. The carrier protein showed good stability and its conformation
      was essentially maintained when conjugated. The T5- and T8-rEPA conjugates were
      of a size range (1-3 x 10(6) g/ mol) consistent with polysaccharide conjugates.
      Fluorescence spectroscopy and molecular sizing showed good batch-to-batch
      consistency. Although all batches of final fill preparations elicited positive
      immune responses in the mouse model with three schedule doses of 0.25 microg of
      each T5/8 conjugate per dose, the mouse serum IgG response to T8 PS varied from
      batch to batch. Storage temperature at 37 degrees C or below or with repetitive
      temperature fluctuations did not significantly affect the IgG responses to T5 or
      T8 PS. Storage at 56 degrees C, however, diminished the mouse serum IgG response
      to T5 PS. The conformation of the conjugated protein and size of the conjugates
      correlated well with mouse immunogenicity in the thermal stability samples;
      significant unfolding of the protein and downshifts in molecular size of the
      conjugate were only observed when stored at 56 degrees C. The relatively high
      stability of the novel carrier protein when conjugated to large polysaccharides
      makes this an attractive candidate carrier protein for other conjugate vaccines.
      When assayed for serum IgG concentration, the bivalent T5/ 8 conjugate was found
      to evoke an IgG response well over the threshold value of 10 microg/ ml anti-T5
      and -T8 IgG established for the ELISA immunogenicity assay.

PMID- 17012904
TI  - Prevalence of pneumococcal bacteremia among children <36 months of age presenting
      with moderate fever to pediatric emergency rooms of the Metropolitan Region
      (Santiago), Chile.
AB  - Blood culture collection from outpatients < age 36 months with high fever (>40
      degrees C, rectal) became a standard of ambulatory care in Emergency Rooms (ERs)
      of the government Children's Hospitals in Chile's Metropolitan Region (MR) in
      1999; thereafter, invasive pneumococcal disease (IPD) incidence doubled over
      preceding years' estimates limited to hospitalizations. We studied IPD among
      children with moderate (>39 degrees C but <40 degrees C, rectal) rather than high
      fever visiting Pediatric ERs. Recruitment ensued Monday to Friday, 1-5 PM,
      September 1, 2002 through August 31, 2003. Age <36 months; rectal temperature >39
      degrees but <40 degrees C; outpatient management; parental consent for
      hemoculture were inclusion criteria. Thirteen-thousand five hundred seventy-seven
      children < age 36 months with moderate and 3,214 children with high fever sought
      ER care. Of 1,134 moderate fever children seen in ERs during the enrollment,
      parents of 837 consented (73.8%). During these days and hours, 714 children < age
      36 months presented with high fever and 651 (91.2%) had a "routine" blood
      culture. Pneumococcemia was detected among 0.7% with moderate and 1.2% with high
      fever (6/837 vs 8/651, p > 0.05). Extrapolating these rates to all ER outpatients
      < age 36 months with moderate and high fever, we estimate the true burden as 95
      and 39 cases, respectively. The burden of pediatric IPD in the MR is currently
      underestimated because bacteremias among ER outpatients with moderate fever are
      not detected. If blood cultures were systematically collected from outpatients
      with moderate fever, recorded pediatric IPD burden would rise >2-fold. However,
      economic and logistical constraints preclude such a practice.

PMID- 17012905
TI  - Comparison of rabbit and mouse models for persistence analysis of plasmid-based
      vaccines.
AB  - Experiments were conducted with a cationic lipid-formulated pDNA vaccine (VCL
      AB01) to evaluate the models used to determine biodistribution, persistence and
      the potential for integration (into genomic DNA) of plasmid DNA-based vaccines.
      Mice were injected with a high-dose volume of 50 microL unilaterally containing
      approximately 1.33 x 10(13) plasmid copy numbers (PCN) or a low-dose volume of 20
      microL bilaterally ( approximately 5.3 x 10(12) PCN). Rabbits were injected
      bilaterally with a 0.5 mL ( approximately 1.33 x 10(14) PCN) volume. Injection
      site muscle tissue was harvested two days, one month, and two months
      postinjection for the low-dose murine and rabbit models and two days and two
      months postinjection for the high-dose murine model. Total DNA was extracted and
      analyzed by real-time quantitative PCR for sequences specific to the injected
      pDNA. The geometric mean PCN/microg of total DNA from the high and low dose
      models were compared to determine if injection volume impacts clearance and/or
      persistence. Results from these studies showed that PCN clearance over two months
      was similar in mice injected with 20 microL and rabbits injected with 0.5 mL, but
      PCN clearance was slower in mice injected with similar PCN in 50 microL (1.33 x
      10(13) PCN) compared to 20 microL (5.3 x 10(12) PCN). Persistence at two months
      in the rabbit and low-dose murine models was comparable, with geometric mean of
      5.22 x 10(3) PCN/microg of total DNA for the low-dose volume murine model and
      2.81 x 10(3)/microg DNA for the rabbit model. Interanimal variability in
      persistence was not impacted by dose volume.

PMID- 17012906
TI  - Cancer vaccines targeting carbohydrate antigens.
AB  - Cancer carbohydrate antigens have been surprisingly potent targets for immune
      recognition and attack by antibodies, both because of their abundance at the cell
      surface and their immunogenicity. Antibodies are ideally suited for eradicating
      pathogens from the bloodstream and from early tissue invasion. Passively
      administered and vaccine induced antibodies have accomplished this, eliminating
      circulating tumor cells and systemic or intraperitoneal micrometastases in a
      variety of preclinical models. A series of carbohydrate cancer cell-surface
      differentiation antigens have now been identified and synthesized. Antibodies
      against each can be induced in the majority of vaccinated patients using KLH
      conjugate vaccines with a potent saponin immunological adjuvant. Polyvalent
      vaccines will probably be required due to tumor cell heterogeneity, heterogeneity
      of the human immune response and the correlation between overall antibody titer
      against tumor cells and antibody effector mechanisms. Trials testing the clinical
      impact of these polyvalent vaccines in the adjuvant setting are planned for the
      near future.

PMID- 17012907
TI  - Generalized cutaneous reactions to the anthrax vaccine: preliminary results of
      anthrax vaccine-specific cell mediated immunity and cytokine profiles.
AB  - Over two years, the Vaccine Adverse Event Reporting System reported that 0.042%
      of all anthrax vaccine (Biothrax, Bioport Corporation) doses administered were
      associated with cutaneous reactions, half of which were eczematous. This case
      series attempts to immunologically detail this eczematous reaction in four
      patients by measuring anthrax vaccine-specific cell mediated immunity (ASCMI),
      profiling TH1 and TH2 cytokine response to the anthrax vaccine in vitro, and
      analyzing of skin biopsy specimens. Results demonstrated that (1) ASCMI was
      variable and likely unrelated to this reaction; (2) a lack of TH1 cytokine
      response to anthrax vaccine may be associated with an increased risk of this
      eczematous reaction; and (3) skin biopsy findings were nonspecific but supportive
      of a clinical diagnosis of eczema. Future studies with more patients may yield
      data to further characterize the ASCMI response and cytokine profiles among
      patients with this type of reaction.

PMID- 17012908
TI  - Bell's palsy and parenteral inactivated influenza vaccine.
AB  - Concern about a possible increased risk of Bell's palsy after parenteral
      inactivated influenza vaccine was raised following the publication in 2004 of a
      Swiss study in which there was an increased risk following the nasal inactivated
      formulation of the vaccine. When data from passive reporting systems in the
      United States and the United Kingdom were examined there was some evidence of
      increased reporting following the parenteral vaccine. A large population based
      study using the General Practice Research Database (GPRD) was therefore performed
      to test the hypothesis that there was an increased risk of Bell's palsy in the
      three months following parenteral inactivated influenza vaccine. The risk was
      also assessed for the same period following pneumococcal vaccine and was
      stratified into three age groups (<45, 45-64 and 65+ years). Relative incidence
      (RI) estimates were calculated using the self-controlled case-series method and
      showed no evidence of an increased risk in the three months following parenteral
      inactivated influenza vaccine RI 0.92 (95% confidence interval 0.78-1.08). There
      was also no evidence of an increased risk in any age group or following
      pneumococcal vaccine. A significant increase was seen on the day of vaccination
      (day 0) probably due to opportunistic recording of cases.

PMID- 17012909
TI  - Development, characterization and immunogenicity of a multi-stage, multi-valent
      Plasmodium falciparum vaccine antigen (FALVAC-1A) expressed in Escherichia coli.
AB  - A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen
      (FALVAC-1A) was designed and evaluated in silico, and then the gene was
      constructed and expressed in Escherichia coli. The FALVAC-1A protein was purified
      by inclusion body isolation, followed by affinity and ion exchange
      chromatography. Although FALVAC-1A was a synthetic antigen, it folded to a
      specific, but as yet incompletely defined, molecular conformation that was stable
      and comparable from lot to lot. When formulated with four different adjuvants,
      FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISA reactivity
      to the cognate antigen and most of its component epitopes, but also in vitro
      activity against P. falciparum parasites as demonstrated by inhibition of
      sporozoite invasion, antibody dependent cellular inhibition and the
      immunofluorescence assay.

PMID- 17012911
TI  - Multiple-drug-resistant bacteria in patients with severe acute exacerbation of
      chronic obstructive pulmonary disease: Prevalence, risk factors, and outcome.
AB  - OBJECTIVE: To determine prevalence, risk factors, and effect on outcome of
      multiple-drug-resistant (MDR) bacteria in patients with severe acute exacerbation
      of chronic obstructive pulmonary disease. DESIGN: Prospective, observational,
      cohort study. SETTING: Thirty-bed medical intensive care unit (ICU) in a
      university hospital. METHODS: All chronic obstructive pulmonary disease patients
      with acute exacerbation who required intubation and mechanical ventilation for
      >48 hrs were eligible during a 4-yr period. Patients with pneumonia or other
      causes of acute respiratory failure were not eligible. In all patients,
      quantitative tracheal aspirate was performed at ICU admission (positive at 10
      colony-forming units [cfu]/mL). MDR bacteria were defined as methicillin
      resistant Staphylococcus aureus, ceftazidime- or imipenem-resistant Pseudomonas
      aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended
      spectrum beta-lactamase-producing Gram-negative bacilli. All patients received
      empirical antibiotic treatment at ICU admission. Univariate and multivariate
      analyses were used to determine variables associated with MDR bacteria and
      variables associated with ICU mortality. RESULTS: A total of 857 patients were
      included, and 304 bacteria were isolated (>/=10 cfu/mL) in 260 patients (30%),
      including 75 MDR bacteria (24%) in 69 patients (8%). When patients with MDR
      bacteria were compared with patients without MDR bacteria, previous antimicrobial
      treatment (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.2-4.7; p =
      .013) and previous intubation (OR, 31; 95% CI, 12-82; p < .001) were
      independently associated with MDR bacteria. When patients with bacteria other
      than MDR or patients with no bacteria were used as a reference group, these risk
      factors were still independently associated with MDR bacteria. Although ICU
      mortality rate was higher in patients with MDR bacteria than in patients without
      MDR bacteria (44% vs. 25%; p = .001; OR, 2.3; 95% CI, 1.4-3.8), MDR bacteria were
      not independently associated with ICU mortality. Inappropriate initial antibiotic
      treatment (88% vs. 5%; p = <.001; OR, 6.7; 95% CI, 3.8-12) and ventilator
      associated pneumonia (23% vs. 5%; p = <.001; OR, 1.3; 95% CI, 1-1.8) rates were
      significantly higher in patients with MDR bacteria than in patients with bacteria
      other than MDR. Inappropriate initial antibiotic treatment was independently
      associated with increased ICU mortality (OR, 7.1; 95% CI, 1.9-30; p = .003).
      CONCLUSION: MDR bacteria are common in patients with acute exacerbation of
      chronic obstructive pulmonary disease requiring intubation and mechanical
      ventilation. Previous antimicrobial treatment and previous intubation are
      independent risk factors for MDR bacteria. Although MDR bacteria are not
      independently associated with ICU mortality, inappropriate initial antibiotic
      treatment is an independent risk factor for ICU mortality in these patients.
      Further studies are needed to determine whether broad-spectrum antibiotic
      treatment is cost-effective in these patients.

PMID- 17012910
TI  - Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in
      rats.
AB  - OBJECTIVE: Nondepolarizing neuromuscular blocking agents are commonly used in the
      intensive care setting, but they have occasionally been associated with
      development of myopathy. In addition, diaphragmatic atrophy and a reduction in
      diaphragmatic force were reported after short-term controlled mechanical
      ventilation in animal models. We hypothesized that infusion of rocuronium, an
      aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled
      mechanical ventilation would further alter diaphragm function and would enhance
      activation of the ubiquitin- proteasome pathway. DESIGN: Randomized, controlled
      experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats,
      14 wks old. INTERVENTIONS: Rats were divided into four groups: a control group, a
      group of anesthetized rats breathing spontaneously for 24 hrs, and two groups
      submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion
      of either 0.9% NaCl or rocuronium. MEASUREMENTS AND MAIN RESULTS: In vitro
      diaphragm force was decreased more significantly after 24 hrs of mechanical
      ventilation combined with rocuronium infusion than after mechanical ventilation
      alone (e.g., tetanic force, -27%; p < .001 vs. mechanical ventilation).
      Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more
      pronounced after mechanical ventilation with rocuronium treatment than with
      saline treatment (-38% and -29%, respectively; p < .001 vs. control). Diaphragm
      hydroperoxide levels increased similarly in both mechanically ventilated groups.
      Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3
      ligase of the ubiquitin-proteasome pathway, increased after mechanical
      ventilation (+212%, p < .001 vs. control) and increased further with combination
      of rocuronium (+320%, p < .001 vs. control). Significant correlations were found
      between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber
      dimensions. CONCLUSIONS: Infusion of rocuronium during controlled mechanical
      ventilation leads to further deterioration of diaphragm function, additional
      atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the
      diaphragm, which suggests an activation of the ubiquitin-proteasome pathway.
      These findings could be important with regard to weaning failure in patients
      receiving this drug for prolonged periods in the intensive care unit setting.

PMID- 17012912
TI  - A comparative study between transmission electron microscopy and
      immunofluorescence mapping in the diagnosis of epidermolysis bullosa.
AB  - The classification of epidermolysis bullosa (EB) into 3 main subtypes has been
      based on transmission electron microscopy (TEM) that is able to directly
      visualize and quantify specific ultrastructural features. Immunofluorescence
      antigenic mapping (IFM) is a technique that determines the precise level of skin
      cleavage by determining binding sites for a series of antibodies. To date, no
      study has compared the accuracy of these two techniques in diagnosing the major
      types of EB. A prospective cohort of 33 patients thought to have EB on clinical
      grounds had TEM, IFM, and genetic testing performed. The sensitivities and
      specificities of TEM and IFM were calculated compared with the genetic results.
      Of 33 cases, 30 had a positive EB diagnosis. TEM subclassified EB into its three
      major forms in 24/30 cases (80%) and IFM in 29/30 cases (97%). Overall, TEM
      sensitivities and specificities when compared with genetic results were 71% and
      81%, respectively. IFM sensitivities and specificities when compared with genetic
      results were 97% and 100%, respectively. If a patient tested positive for EB by
      IFM, the likelihood ratio of having a particular type of EB was consistently
      greater than 20 against the reference standard (compared with a likelihood ratio
      less than 10 for TEM). Our results indicate that the diagnosis of EB is improved
      (sometimes substantially) by the use of IFM compared with TEM.

PMID- 17012913
TI  - Papillated Bowen disease, a distinct variant.
AB  - Bowen disease usually presents as an irregular, asymptomatic, scaly or crusted
      erythematous plaque that can occur anywhere on the skin. An unusual
      clinicopathologic variant is described which presents as a well-circumscribed,
      papillated, exophytic and endophytic, sometimes keratotic lesion. This papillated
      variant of Bowen disease exhibits keratinocytes with prominent perinuclear halos
      suggestive of koilocytic change associated with human papillomavirus (HPV)
      infections. Classic Bowen disease has been associated in previous studies with a
      variety of HPV types, especially types 16, 18, and 31. Twenty-six patients with
      papillated Bowen disease were evaluated. The patients included 15 males and 11
      females, ranging in age from 33 to 87 years old. Fifty-four percent (14) of the
      lesions involved the head and neck, 8% (2) involved the trunk, and the remaining
      38% (10) involved extremities (including 3 lesions from the hands). Lesions were
      examined using in situ hybridization with widely screening genomic probes for HPV
      types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52. None of the specimens
      contained HPV DNA from the more common oncogenic HPV types. Given the striking
      histologic appearance of these lesions, however, this does not exclude HPV
      infection detectable by more sensitive screening methods such as polymerase chain
      reaction. Papillated Bowen disease is distinct from other variants, including the
      verrucous-hyperkeratotic type.

PMID- 17012914
TI  - Primary cutaneous lymphoproliferative disorders with dual lineage rearrangement.
AB  - We present a series of 15 cases of cutaneous lymphoma and pseudolymphoma with
      dual lineage rearrangement identified among approximately 1200 cases of cutaneous
      lymphoproliferative disorders assessed in our 4 institutions during the last 8
      years in which the results of both T-cell receptor and immunoglobulin heavy chain
      rearrangement investigations were available. On the basis of the
      clinicopathologic information, the cases were retrospectively subdivided into 2
      categories: (1) cases with definite features of cutaneous lymphoma or
      pseudolymphoma (n = 11) and (2) cases with unclassifiable disease (n = 4). The
      detection of dual genotype in the first group did not influence the final
      diagnosis; 7 cases represented cutaneous B-cell lymphomas, 3 pseudolymphomas, and
      1 case lymphomatoid papulosis. The presence of monoclonal T-cell receptor-gene
      rearrangements in these cases may be explained either by monoclonal or
      oligoclonal expansion of exuberant T cells (or B cells in case of lymphomatoid
      papulosis) or by lineage infidelity. Three patients with unclassifiable disease
      had several clinical and histopathologic features in common. They were elderly,
      presented with solitary lesions, were in good general health and
      histopathologically demonstrated a dense multinodular infiltrate containing
      approximately an equal number of T and B cells and a high number of histiocytes
      forming granulomas, with prominent granulomatous features in 2 cases. B cells
      were either scattered with the infiltrate or formed collections vaguely
      resembling follicles; Reed-Sternberg-like cells were seen in 2 cases. B cells
      showed expression neither of immunoglobulin light chain. The T-cell component was
      represented mainly by small, well-differentiated lymphocytes or slightly
      pleomorphic cells, with some medium-sized convoluted cells. Epstein-Barr virus
      was not detected by polymerase chain reaction. The exact classification of these
      cases is unknown; they differ histopathologically from previously published cases
      of bigenotypic cutaneous lymphomas. They may merely represent a growth or
      reactive pattern, but, on the other hand, may be low-grade lymphomas. If so, they
      may be histopathologically related to cutaneous Hodgkin disease, T
      cell/histiocyte-rich large B-cell lymphoma, or composite lymphomas. Further
      reports are needed to identify these lesions to clarify their nature and biologic
      potential.

PMID- 17012915
TI  - Expression of ERp29, an endoplasmic reticulum secretion factor in basal-cell
      carcinoma.
AB  - The role of endoplasmic reticulum (ER)-stress proteins in the pathogenesis of
      neoplasia remains obscure. ERp29 encodes for an ER protein that is thought to
      facilitate the transport of secretory proteins in the early secretory pathway.
      ERp29 is expressed at varying levels in virtually every tissue tested, yet its
      precise role remains obscure. To test if ERp29 is associated with the
      pathogenesis of skin cancer, in the present study we have assessed the expression
      of ERp29 in basal-cell carcinoma of the skin. A bank of 104 basal skin carcinoma,
      including 50 nodular, 29 infiltrating, 15 superficial, 7 sclerosing, 2
      fibroepithelial, and 1 pigmented cell carcinoma, were assessed by
      immunohistochemistry for ERp29 expression. Thirty-nine (37.5%) of the samples
      tested expressed ERp29 with the infiltrating carcinomas displaying more intense
      (++,+++) immunoreactivity (6/29, P < 0.05) and the superficial carcinomas
      exhibiting the less intense anti-ERp29 staining (1/15, P < 0.05). Collectively
      our results suggest that ERp29 is expressed in a subset of basal-cell carcinoma
      of the skin with the infiltrating carcinomas exhibiting the highest incidence of
      immunopositivity. The role of ERp29 in the pathogenesis of the disease and its
      potential diagnostic value should be explored in future investigations.

PMID- 17012916
TI  - Teledermatopathology: a controlled study about diagnostic validity and technical
      requirements for digital transmission.
AB  - Telepathology is the practice of diagnostic histopathology performed on digital
      pictures. In this study, we focused on the technical requirements for achievement
      of a correct diagnosis on digital histopathologic images. A collection of 560
      melanocytic lesions was selected from the files of the Department of Dermatology,
      Medical University of Graz, Austria. From each lesion one histologic slide was
      completely digitally scanned with a robotic microscope. Digital pictures were
      reviewed by 4 dermatopathologists using a presentation program, which recorded
      the number of image calls, applied magnifications, overall time needed, and
      amount of transmitted bits during the digital sign-out. One month later, the 4
      microscopists had to review the corresponding slides and render a direct
      diagnosis on each case. Telepathologic diagnoses corresponded with the original
      diagnoses in a range from 90.4% to 96.4% of cases (kappa 0.80 to 0.93; P <
      0.001). The median time needed for achievement of a diagnosis was 22 seconds and
      was significantly higher for melanomas compared with nevi. The median
      transmission effort for each diagnosis was 510 kilobytes after JPEG compression.
      Using an ISDN line with a transmission capacity of 64 kilobits/ second, this
      correlates to a transmission time of about 1 minute. Our results demonstrate that
      correct reporting on digital histopathologic images is possible with only a
      little time exposure. For an adequately fast transmission ISDN lines are
      suffcient after JPEG compression.

PMID- 17012917
TI  - Heat shock proteins (HSP70 and HSP27) as markers of epithelial dysplasia in oral
      leukoplakia.
AB  - Heat shock proteins (HSPs) play a significant role in cell proliferation,
      differentiation, and oncogenesis. HSP70 and HSP27 are constitutively and
      gradually expressed in a broad range of normal tissues and neoplasms, and their
      expression has been assessed as markers for oral epithelial dysplasia. The study
      involved 43 patients with oral leukoplakia (OL): 23 were categorized as
      nondysplastic and 20 as dysplastic OLs. Immunohistochemistry was carried out with
      the monoclonal antibodies HSP70 and HSP27. The presence of epithelial dysplasia
      and its histologic grading was evaluated according to the World Health
      Organization classification: mild, moderate, and severe squamous epithelial
      dysplasia. Expression of HSPs within the epithelium was also evaluated. The
      difference in the percentage of HSP70 positive nuclei in nondysplastic and
      dysplastic OL reached statistical significance(Equation is included in full-text
      article.)95% confidence interval = 17.74-43.82; P = 0.000). None of the 43
      specimens analyzed showed positive nuclear immunostaining for anti-HSP27
      antibody. No significant difference for HSP27 cytoplasmic expression could be
      identified between OL with or without epithelial dysplasia(Equation is included
      in full-text article.)95% confidence interval = 0.44-3.95; P = 0.89). It is
      concluded that the nuclear HSP70 immunoexpression could be an objective marker
      for the presence of the epithelial dysplasia in OL.

PMID- 17012918
TI  - Reexcision perineural invasion: a mimic of malignancy.
AB  - The presence of epithelium in the perineural space is typically associated with
      invasion by malignant tumors. In this report, bland-appearing epithelium was
      identified in the perineural space associated with a dermal reparative reaction
      after removal of a melanoma in 4 patients. After exclusion of possible squamous
      cell carcinoma and immunohistochemistry, a diagnosis of reexcision perineural
      invasion was made. The report illustrates the features of this uncommon and
      little recognized entity which has not been previously reported in the
      dermatology or dermatopathology literature. A lack of appreciation of the
      condition may lead to a misdiagnosis of malignancy, especially squamous cell
      carcinoma. The cases also highlight the need for good clinical correlation when
      examining reexcision specimens. There may be increased recognition of reexcision
      perineural invasion with the rise in reexcisions that are being performed, with
      some surgeons reexcising Spitz nevi and dysplastic nevi, for example.

PMID- 17012919
TI  - Pilomatricomal horn: a new superficial variant of pilomatricoma.
AB  - We describe a pilomatricomal horn on the right arm of a 39-year-old man. Although
      initially the tumor was clinically thought to be a verruca vulgaris, the
      microscopic features were similar to those found in classic pilomatricoma, except
      for the epidermal location and the presence of a cutaneous horn. Light microscopy
      showed replacement of the epidermis by basaloid cells, with masses of cornified
      material containing shadow cells that formed a cutaneous horn. Whereas classic
      pilomatricoma is confined to the deep reticular dermis or subcutis, the present
      case represents a unique heretofore unreported epidermal variant of pilomatricoma
      that pathologists should be aware of to differentiate it from malignant epidermal
      tumors.

PMID- 17012920
TI  - Angiotropism in epidermotropic metastatic melanoma: another clue to the
      diagnosis.
AB  - The diagnosis of epidermotropic metastatic malignant melanoma (EMMM) can be
      extremely challenging for both clinicians and pathologists. The diffculties
      include distinguishing metastatic lesions with an epidermal component from
      residual incompletely excised primary melanoma, and multiple primary melanomas.
      This has great prognostic significance as the current American Joint Committee on
      Cancer guidelines consider localized metastatic disease such as satellites and
      intransits in the nodal (N) category of N2C or stage IIIB disease. In this
      report, we present a case of EMMM with angiotropism. Additionally, we discuss in
      detail the differential diagnosis for recurrence of malignant melanoma with an
      epidermal component within the scar. Angiotropism may be seen in lesions of EMMM
      and the current literature suggests that angiotropism is highly suggestive of
      metastatic melanoma. The differential diagnosis of locally recurrent melanoma
      with an epidermal component can be extremely challenging and the presence of
      angiotropism may be a clue to the diagnosis of EMMM.

PMID- 17012921
TI  - Pleomorphic CD8+ small/medium size cutaneous T-cell lymphoma.
AB  - Pleomorphic small/medium-sized cutaneous T-cell lymphoma is a recently recognized
      rare type of cutaneous T-cell lymphoma which is clinicopathologically different
      from mycosis fungoides and Sezary syndrome. By definition the phenotype of the
      neoplastic lymphocytes in pleomorphic small/medium-sized cutaneous CD3CD4CD8 but
      CD8 pleomorphic small/medium sized cutaneous T-cell lymphoma cases have been
      occasionally described. We describe a 55-year-old female with a pruritic
      erythematous nodule on the lateral aspect of her right foot present for 1.5
      years. Histology revealed a nonepidermotropic lichenoid infiltrate in the
      papillary dermis and a patchy infiltrate in the mid and lower dermis composed of
      small to medium-sized pleomorphic lymphocytes. The immunophenotype of these
      lymphocytes was CD3CD4CD8TIA-1. Staining for CD20, CD30, CD56, TdT, and LMP1 were
      negative, and the Ki-67 proliferation index was 5% to 10%. Gene rearrangement
      studies demonstrated a T-cell clone. The laboratory and imaging workup did not
      reveal extracutaneous involvement. The lesion was treated by local irradiation
      but a follow-up biopsy demonstrated only partial remission. Consequently, the
      lesion was treated by surgical excision.

PMID- 17012922
TI  - Cutaneous B-cell pseudolymphoma due to paraphenylenediamine.
AB  - Lymphomatoid contact dermatitis is a form of pseudolymphoma that was first
      described in 1976 by Orbaneja et al. Since that initial report, a number of
      allergens have been reported to cause this type of pseudolymphoma. Most cases
      involve hyperplasia of T cells. We describe a case of cutaneous B-cell
      pseudolymphoma due to paraphenylenediamine. This report underscores the
      importance of thorough history and observation when assessing patients with
      suspected lymphoproliferative processes.

PMID- 17012923
TI  - Primary cutaneous plasmacytoma (posttransplant lymphoproliferative disorder,
      plasmacytoma-like) in a heart transplant patient.
AB  - Extramedullary plasmacytomas in posttransplant patients are rarely encountered.
      We present the fifth case of a primary cutaneous plasmacytoma (posttransplant
      lymphoproliferative disorder, plasmacytoma-like) that developed in a heart
      transplant patient. The tumor presented as a solitary nodule of the skin 10 years
      after transplantation. It subsequently involved 2 other cutaneous sites and
      remained confined to the skin for 5 years. The neoplastic cells were Epstein-Barr
      virus small RNAs (EBER 1,2) positive and EBV-latent membrane protein 1 (LMP 1)
      negative, corresponding to type I EBV latency. The direct role of EBV in the
      development of the tumor remains uncertain.

PMID- 17012924
TI  - Rippled-pattern sebaceoma: a report of a lesion on the back with a review of the
      literature.
AB  - A 68-year-old Japanese man presented with a nodule that had been present for 5 to
      6 years on the right side of the back. Physical examination revealed a dome
      shaped, 12 x 13-mm, dark red nodule. It was excised with a 2 to 3-mm margin. The
      patient remained free of disease during 77 months of follow-up. Microscopic
      examination revealed a bulb-like tumor in the dermis, contiguous with the
      overlying epidermis. It was composed of small, monomorphous, cigar-shaped
      basaloid cells in linear, parallel rows, resembling the palisading of nuclei of
      Verocay bodies, and presenting a rippled-pattern. There were scattered cells
      showing sebaceous differentiation with vacuolated cytoplasm and scalloped nuclei.
      There were tiny, duct-like spaces. The tumor revealed characteristics of rippled
      pattern sebaceoma. The present case is the first reported rippled-pattern
      sebaceous neoplasm on the back. Many spindle cell tumors, such as basal cell
      carcinoma, pleomorphic adenoma, dermatofibrosarcoma protuberans,
      myofibroblastoma, and leiomyoblastoma, in addition to trichoblastoma and
      sebaceoma, can have a rippled-pattern.

PMID- 17012925
TI  - Intraepidermal dendritic melanocytes in spitzoid neoplasms.

PMID- 17012926
TI  - Dermatopathology in historical perspective: epithelioma cuniculatum (Aird).
AB  - Professor Ian Aird, a renowned British surgeon of the mid-twentieth century,
      described a peculiar neoplasm of the foot in 3 patients under the term
      epithelioma cuniculatum, now more commonly called carcinoma cuniculatum. I will
      recount the life of Professor Aird and then summarize his original report
      emphasizing the clinical and more particularly the histopathologic criteria of
      epithelioma cuniculatum as described by Aird et al. Then I will summarize some of
      the subsequent reports of epithelioma (carcinoma) cuniculatum. Authors have
      grouped carcinoma cuniculatum with giant condyloma of the penis of Buschke
      Loewenstein and oral verrucous carcinoma of Ackerman and similar neoplasms at
      other sites under the generic title "verrucous carcinoma." Although this
      classification has been accepted, I will stress that the clinical picture and
      histopathology described by Aird et al differ from those in later reports of
      carcinoma cuniculatum. These correspond to descriptions of the verrucous
      carcinomas of Buschke-Loewenstein and Ackerman. Finally, I will conclude that
      carcinoma cuniculatum as delineated by Aird and his colleagues is an extremely
      rare, indolent, nonmetastasizing squamous cell carcinoma composed of banal
      keratinocytes with unique clinical and histopathologic features that almost
      always arises on the foot. If a neoplasm on the foot has the characteristics of
      verrucous carcinoma that occurs at others sites, but not those of Aird et al, it
      should be called verrucous carcinoma of the foot, and not "epithelioma
      (carcinoma) cuniculatum."

PMID- 17012930
TI  - Efficacy and cost-effectiveness in dementia interventions: the need for an
      international consensus.

PMID- 17012927
TI  - Monster cells in malignant melanoma.

PMID- 17012931
TI  - Of mice and men: more neurobiology in dementia.
AB  - PURPOSE OF REVIEW: An increasing number of genetically modified mouse models are
      designed and used in the field of Alzheimer disease research. This review aims to
      offer a general view of the existing transgenic mouse lines and to discuss their
      relevance and limitations. RECENT FINDINGS: Potential therapeutic targets have
      been identified in rodent models of Alzheimer disease. Although important steps
      towards obtaining a safe vaccine to prevent amyloid plaque formation have been
      made, further evaluations and the use of intermediate models are considered a
      necessity. SUMMARY: More than 18 million people worldwide are suffering from
      Alzheimer disease, the most common dementing disorder in humans. Transgenic lines
      have been created in order to understand the underlying mechanisms of Alzheimer
      disease and to find a cure. None of the available models completely recapitulates
      the characteristics of human pathology, but they provide valuable information on
      different pathogenic pathways involved. New therapeutic approaches and
      improvement of current strategies can be obtained from the use of Alzheimer
      animal models.

PMID- 17012932
TI  - Seeing is believing: neuroimaging adds to our understanding of cerebral
      pathology.
AB  - PURPOSE OF REVIEW: Recent technological developments in neuroimaging have led to
      new technologies that provide measures of the cerebral pathology of
      neurodegeneration in living humans. The purpose of this review is to provide
      background behind these developments and update readers on new findings. RECENT
      FINDINGS: Several imaging methods using positron emission tomography have
      provided measures of amyloid senile plaques in the brain of demented patients and
      patients with early memory symptoms. ([F-18]FDDNP)-positron emission tomography
      provides measures of both amyloid plaques and neurofibrillary tangles. Initial
      results indicate that the pattern of binding values in Alzheimer's disease is
      consistent with the known neuropathology from autopsy studies, and patients with
      mild cognitive impairment, who are at risk of Alzheimer's disease, show binding
      values intermediate between Alzheimer's disease and normal aging. 2-(1-{6-[(2-[F
      18]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP)
      positron emission tomography also shows a pattern of neuropathology distribution
      for frontotemporal dementia that differs from that of Alzheimer's disease.
      SUMMARY: In-vivo imaging of cerebral pathology offers the potential for more
      effective and earlier diagnosis and use of these technologies as surrogate
      markers to test novel treatments aimed at preventing or eliminating cerebral
      plaque and tangle accumulation.

PMID- 17012933
TI  - 'I think therefore I am': improving cognition.
AB  - PURPOSE OF REVIEW: In the absence of a specific treatment for dementia, the
      effective management of cognitive symptoms is a clinical priority. RECENT
      FINDINGS: Although some differences have been observed in the profile of
      cognitive complaints observed in subtypes of dementia, there is increasing
      recognition of common, interacting neurobiological causes suggesting the need to
      seek a common treatment applicable to all causes of cognitive deterioration.
      There also exists increasing interest in intervening at the level of minor
      cognitive dysfunction by reducing risk factors for subclinical states. SUMMARY:
      Pharmacological treatment of cognitive disorder is beneficial but has only
      temporary benefit for a subgroup of patients. Pharmacogenetics may have an
      important future role to play in deciding which patients may best benefit from
      the treatment. Low side effect therapies such as cognitive therapy and
      acupuncture show some benefits but their utility in combination with
      pharmacotherapies remains to be demonstrated. Prevention of milder forms of
      cognitive disorder by controlling risk factors such as hypertension and diabetes
      may reduce rates of more severe cognitive degeneration. Persons with cognitive
      dysfunction are commonly excluded from making decisions about the implementation
      of cognition-enhancing treatments although they wish to do so.

PMID- 17012934
TI  - Treatment of dementia: anything new?
AB  - PURPOSE OF REVIEW: The aim of this article is to discuss new data on presently
      approved drugs for dementia, such as cholinesterase inhibitors and memantine, and
      concerns regarding the use of antipsychotics for treating neuropsychiatric
      symptoms, as well as to summarize some relevant studies recently published on
      emerging therapies with potential disease-modifying effects. RECENT FINDINGS: The
      main focuses of recent studies of cholinesterase inhibitors and memantine have
      been on efficacy and safety aspects in extended clinical trials, combined
      treatments or comparative analysis between agents, and also on potential
      neuroprotective effects and new indications. Other publications have assessed the
      evidence of efficacy and the increased risk of cerebrovascular events, rapid
      cognitive decline, and mortality with the use of antipsychotics in dementia,
      providing important information in relation to the controversy surrounding its
      use. Although more studies are warranted, a sizable literature on novel treatment
      options under investigation is currently available as a result of a better
      understanding of pathogenesis of dementia. SUMMARY: So far, there is no
      established method to predict better responders or long-term benefits with
      currently approved drugs for treatment of dementia. Recent systematic reviews and
      new research on current treatment, however, provide valuable information for
      clinicians, and novel drugs under investigation reveal promising new therapeutic
      strategies.

PMID- 17012935
TI  - The neurobiology of neuropsychiatric syndromes in dementia.
AB  - PURPOSE OF REVIEW: Neuropsychiatric disturbances in dementia are prevalent, and
      research is uncovering their neurobiological correlates. RECENT FINDINGS: Late
      onset depression appears to be associated with Alzheimer's disease pathology at
      autopsy, and lifetime depression episodes may worsen Alzheimer's disease
      pathology in the hippocampus. Vascular disease and elevated homocysteine increase
      risk for both late-onset depression and Alzheimer's disease and may partly
      mediate their relationship. Monoamine changes are robust finding in Alzheimer's
      disease and may account for many observed depression symptoms. Risk of psychosis
      of Alzheimer's disease appears to be increased by several genes also implicated
      in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in
      dementia with Lewy bodies appears to be related to cholinergic deficits.
      Alzheimer's disease is associated with changes in the circadian sleep-wake
      cycles, including decreased night-time melatonin. Sleep apnea may be related to
      apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye
      movement sleep behavior disorder is intricately related to synucleinopathies,
      such as dementia with Lewy bodies, but synuclein changes may not totally explain
      this relationship. SUMMARY: Neuropsychiatric disturbances are a core feature of
      dementia and worsen many clinical outcomes. Among the most validated syndromes
      are depression, psychosis, and sleep disturbance of Alzheimer's disease.
      Neuropathology, neuroimaging, and genetic studies increasingly provide insight
      into the origins of these psychiatric symptoms in dementia.

PMID- 17012936
TI  - Prevalence, risk factors and treatment for substance abuse in older adults.
AB  - PURPOSE OF REVIEW: This paper briefly outlines new research on the epidemiology
      of alcohol and drug use in the older population, describes mental and cognitive
      consequences of substance use and summarizes recent treatment trials for alcohol
      dependence. RECENT FINDINGS: Cross-sectional and longitudinal studies indicate
      that alcohol use is less prevalent in older groups, and it decreases over time.
      Comorbidity (alcohol and other drugs, alcohol with mental health disorders) is
      high. An inverse-U-shaped curve describes the association between alcohol
      consumption and cognitive impairment with increased impairment for abstainers and
      high users as compared with moderate users. Trials of alcohol use in the older
      population are rare, but they suggest that brief patient education may reduce
      drinking levels in primary care populations, and that, for some users, integrated
      primary care may be more useful than referral to specialist care. SUMMARY: The
      basis for higher risk in abstainers is not resolved. More randomized controlled
      trials are needed, which target alcohol use and dependence and also focus on
      comorbid disorders.

PMID- 17012939
TI  - Ethical issues in neuroscience.
AB  - PURPOSE OF REVIEW: The study gives an overview of ethical questions raised by the
      progress of neuroscience in identifying and intervening in neural correlates of
      the mind. RECENT FINDINGS: Ethical problems resulting from brain research have
      induced the emergence of a new discipline termed neuroethics. Critical questions
      concern issues, such as prediction of disease, psychopharmacological enhancement
      of attention, memory or mood, and technologies such as psychosurgery, deep-brain
      stimulation or brain implants. Such techniques are capable of affecting the
      individual's sense of privacy, autonomy and identity. Moreover, reductionist
      interpretations of neuroscientific results challenge notions of free will,
      responsibility, personhood and the self which are essential for western culture
      and society. They may also gradually change psychiatric concepts of mental health
      and illness. These tendencies call for thorough, philosophically informed
      analyses of research findings and critical evaluation of their underlying
      conceptions of humans. SUMMARY: Advances in neuroscience raise ethical, social
      and legal issues in relation to the human person and the brain. Potential
      benefits of applying neuroimaging, psychopharmacology and neurotechnology to
      mentally ill and healthy persons have to be carefully weighed against their
      potential harm. Questions concerning underlying concepts of humans should be
      actively dealt with by interdisciplinary and public debate.

PMID- 17012940
TI  - Conceptual issues in psychiatric neuroimaging.
AB  - PURPOSE OF REVIEW: Psychiatric neuroimaging has made a dramatic impact on the
      understanding of the brain in mental illness in a relatively brief period of time
      and continues to be evolving in terms of methodology, analysis and utilization of
      the combination of techniques. Given the level of sophistication of the
      techniques and the importance of imaging in current academic psychiatry, it is
      timely to review its conceptual influence on psychopathology. RECENT FINDINGS:
      The study will review scientific advances in psychiatric neuromaging, around the
      themes of functional connectivity, diffusion tensor imaging,
      magnetoencephalography, modality integration, meta-analyses and mega-analyses of
      data and discuss recent influential findings in contemporary research. We then
      focus on more conceptual issues relating to biological psychiatry and its
      relationship with cognitive neuroscience. We discuss the dominant paradigm of
      scientific psychopathology, namely cognitive neuropsychiatry and how it relates
      more broadly to imaging and cognitive science and elaborate on the philosophical
      positions of the paradigm and how it views abnormal mental states. SUMMARY: We
      conclude that despite the advances in biological psychiatry and the power of the
      cognitive neuropsychiatry paradigm, its findings are logically contingent upon
      psychopathology and the normatively defined terms employed therein.

PMID- 17012941
TI  - Conceptual issues in undifferentiated somatoform disorder and chronic fatigue
      syndrome.
AB  - PURPOSE OF REVIEW: To review the conceptual problems in distinguishing between
      undifferentiated somatoform disorder and chronic fatigue syndrome, for both may
      present with fatigue as the main symptom. RECENT FINDINGS: The differences and/or
      similarities between undifferentiated somatoform disorder and chronic fatigue
      syndrome have not been studied, conceptually or empirically. The literature fails
      to present discriminant validity of chronic fatigue syndrome in relation to
      undifferentiated somatoform disorder. A critical feature is implied in the
      definition of undifferentiated somatoform disorder but absent from the
      definitions of chronic fatigue syndrome: some patients experience their fatigue
      as being exclusively physical and not as mental, which is prima facie peculiar,
      for fatigue is necessarily a mental experience. One is not able to experience
      fatigue without a mind (or a brain). This experience is characterized as a
      'mindless' fatigue, underpinned by pathological reductionist thinking. By not
      recognizing this critical feature, diagnostic endeavours may perpetuate the
      problem as a function of the patient's difficulty. SUMMARY: Proponents of chronic
      fatigue syndrome should distinguish chronic fatigue syndrome from
      undifferentiated somatoform disorder, if chronic fatigue syndrome is a distinct
      entity at all. Further, the 'mindless' quality is a critical feature that needs
      consideration in refining the concept of undifferentiated somatoform disorder.

PMID- 17012942
TI  - Paradigms of psychiatry: eclecticism and its discontents.
AB  - PURPOSE OF REVIEW: To assess paradigms of psychiatry, assessing their strengths
      and limitations. RECENT FINDINGS: The biopsychosocial model, and eclecticism in
      general, serves as the primary paradigm of mainstream contemporary psychiatry. In
      the past few decades, the biopsychosocial model served as a cease-fire between
      the biological and psychoanalytic extremism that characterized much of the 19th
      and 20th century history of psychiatry. Despite being broad and fostering an
      'anything goes' mentality, it fails to provide much guidance as a model. In
      recent years, the biological school has gained prominence and now is under attack
      from many quarters. Critics tend toward dogmatism themselves, usually of
      postmodernist or libertarian varieties. Three alternate approaches include
      pragmatism, integrationism, and pluralism. Pluralism, as technically defined here
      based on the work of Karl Jaspers, rejects or accepts different methods but holds
      that some methods are better than others for specific circumstances or
      conditions. SUMMARY: The compromise paradigm of biopsychosocial eclecticism has
      failed to sufficiently guide contemporary psychiatry. The concurrent revival of
      the biological model has led to postmodernist counter-reactions which, though
      valid in many specifics, promise to replace one ideological dogma with another.
      New paradigms are needed.

PMID- 17012943
TI  - Bias in psychopathology research.
AB  - PURPOSE OF REVIEW: Biases are frequently invoked in psychopathology research,
      either as core features of particular forms of psychopathology or as errors and
      distortions that affect psychiatric assessment, diagnosis, treatment, and
      research methodology. This review provides an overview of recent research on the
      forms of bias that are commonly examined in the field. RECENT FINDINGS: Recent
      research has made a number of advances in the analysis of cognitive and affective
      biases underpinning psychopathology: the effect of rating and other biases on
      psychiatric assessment and diagnosis; the role of race and gender in psychiatric
      practice; financial and institutional influences on psychiatric services; and
      several biases affecting research methodology, study design, and statistical
      inference. SUMMARY: Bias has several distinct meanings, and encompasses a
      disparate set of phenomena, so no over-arching conclusion about the place of bias
      in psychopathology research can be drawn. Recent work, however, makes solid
      progress toward a better understanding of systematic distortions and how they can
      be recognized and reduced.

PMID- 17012944
TI  - Innovations in agonist maintenance treatment of opioid-dependent patients.
AB  - PURPOSE OF REVIEW: To provide an overview of published studies on agonist
      maintenance treatment options for opioid-dependent patients. RECENT FINDINGS: The
      recent publication of controlled trials confirms earlier clinical evidence of the
      efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings
      show not only efficacy with respect to improvement of health, reduction of
      illicit drug use, reduction of criminality and stabilization of social
      conditions, but also cost effectiveness in the treatment of chronic treatment
      resistant heroin addicts. SUMMARY: Agonist maintenance treatment has become the
      first-line treatment for chronic opioid dependence. High-quality studies
      demonstrate the effectiveness of a growing number of different agonist
      maintenance treatments for opioid dependence such as methadone and buprenorphine.
      In addition, there is new evidence for the effectiveness of other agonists,
      mainly slow-release morphine, intravenous and inhalable diamorphine and possibly
      oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine
      should be implemented into the healthcare system to treat a group of severely
      dependent treatment-resistant patients. Furthermore, the opioid-dependent
      patients not under treatment need to be engaged in maintenance treatments through
      other harm reduction measures. Agonist maintenance treatment is very effective in
      stabilizing the health condition and social situation, while also reducing harm,
      thereby increasing life expectancy and quality of life.

PMID- 17012945
TI  - Insight and quality of life in schizophrenia: recent findings and treatment
      implications.
AB  - PURPOSE OF REVIEW: Several studies have reported that patients with schizophrenia
      lack awareness of having a mental disorder or symptoms of a mental disorder. The
      concept of insight has long been considered important for engagement in
      treatment, psychotherapeutic progress and good prognosis. RECENT FINDINGS:
      Contradictory results were found regarding the relationship between insight into
      illness and quality of life in patients with schizophrenia. Although previous
      studies found an inverse or no significant association, recent studies reported
      that greater insight into illness is significantly associated with an increase in
      depression and poor subjective quality of life. SUMMARY: Patients with good
      insight might realize their restrictions more clearly. The stigma of being
      mentally ill and the need for treatment or hospitalization are serious
      psychological strains. The increase of depression and suicidal ideation and
      decrease in subjective quality of life in patients with better insight underline
      the importance of insight for the clinical course in schizophrenia. The inclusion
      of modules focussing on depressive symptoms and quality of life-related aspects
      to psychoeducational programmes, as well as a greater awareness of the physician
      for these questions and a strengthening of the therapeutic alliance, might help
      improve insight without the risk of deteriorating mood and quality of life.

PMID- 17012946
TI  - Pharmacological treatment of non-Alzheimer dementias.
AB  - PURPOSE OF REVIEW: One hundred years after the first description by Alois
      Alzheimer and with the advent of first pharmacological treatments, most
      researchers concentrate on Alzheimer's disease. Millions of patients, however,
      suffer from other dementias and search for help beyond diagnosis. RECENT
      FINDINGS: New clinical data concerning the treatment of non-Alzheimer dementias
      mainly relate to the clinical use of antidementiva that is already approved for
      the treatment of Alzheimer's disease. Few studies test new pharmacological
      paradigmata. For some forms like vascular dementias, the possibility of
      prevention is the most valuable approach that should be enforced more
      aggressively. For other savaging dementias new unconventional treatment trials
      should be encouraged. SUMMARY: Research for non-Alzheimer dementias lags behind
      those for the Alzheimer field. For many patients, we still have nothing but
      words. At the same time, probably with regard to cost constraints, some acteurs
      like health insurances and legislators are inclined to nurture therapeutic
      nihilism and cultivate ethical qualms and demurs instead of supporting clinical
      trials or at least not blocking them with bureaucratic hand-cuffs, whereas
      pharmaceutical companies contemplate naturally over questions like return of
      investment. The clinical researchers should fight this fatigue and look for ways
      out of this quagmire for our patients.

PMID- 17012947
TI  - Bibliography. Current world literature. Geriatric psychiatry.

PMID- 17012950
TI  - Infection control matters in home healthcare.
AB  - Infection control is pivotal to good nursing care in any setting. This column is
      dedicated to new developments in infection control that specifically affect home
      healthcare nursing.

PMID- 17012951
TI  - The ABCs of teaching older adults: implications for home care and hospice.

PMID- 17012953
TI  - Using record review as a quality improvement process.
AB  - A patient's record is a repository of personal data, the plan of care, and
      documentation of assessment and treatment. The record review process can
      facilitate a clinician's understanding about documentation standards and
      requirements as well as help to maintain a state-of-audit readiness of the record
      for regulatory and accrediting surveys.

PMID- 17012955
TI  - An analysis of the differences between hospital and home healthcare nurse job
      satisfaction.

PMID- 17012956
TI  - The Family Caregiver Program: design and effectiveness of an education
      intervention.
AB  - How can family caregivers develop the knowledge and confidence necessary to be
      successful in providing care to their loved ones at home? This article describes
      a formal education program for family caregivers, created by Winchester
      Hospital's Community Health Institute in Massachusetts, to meet their needs. The
      article also describes a study that Winchester Hospital's Community Health
      Institute undertook to evaluate the effectiveness of this education program on
      increasing the skills and confidence of family caregivers.

PMID- 17012957
TI  - The caring behaviors of the home health nurse and influence on medication
      adherence.
AB  - The purpose of this study was to determine if the caring behaviors of the home
      health nurse toward the patient influence the patient's medication adherence. The
      study focused on what effects the verbal and nonverbal caring behaviors of the
      nurse toward the patient have on the patient's medication adherence. How is the
      patient's perception of caring by the nurse related to his or her medication
      adherence? The study was conducted in a Midwestern home health agency over a 4
      week period. Findings indicated an improvement in the use of verbal and nonverbal
      caring behaviors by the nurses with their patients. The patients perceived an
      increased use of these caring behaviors by the nurses with them. The patients'
      medication adherence and barriers to adherence improved. Other significant
      findings indicated that the verbal and nonverbal caring behaviors of the nurses
      and the patients' perception of the caring behaviors influenced and improved the
      patients' medication adherence by week 4.

PMID- 17012958
TI  - Technology in hospice: is it a contradiction?

PMID- 17012960
TI  - Better technology means better care.

PMID- 17012959
TI  - Low-technology heart failure care in home health: improving patient outcomes.
AB  - This article reports a study that pilot tested the effectiveness of a low
      technology structured intervention to standardize home healthcare management of
      patients with heart failure (HF) within a home health agency (HHA). The purpose
      of this study was to use low-technology equipment to improve care for patients
      with HF enrolled in a home health agency. The 9-week intervention was targeted
      toward the home health nurses and included telephone and home visits, a teaching
      tool, digital scales, and a log/notebook filled out by the patients in the study.
      Patient outcomes included decreased rehospitalization, decreased symptoms of HF,
      and increased quality of life.

PMID- 17012961
TI  - Portable technology and the portable nurse.

PMID- 17012962
TI  - Environmental factors in inflammatory bowel disease: a co-twin control study of a
      Swedish-Danish twin population.
AB  - BACKGROUND: Genetics and environmental factors are implicated in the etiology of
      inflammatory bowel disease (IBD). We studied environmental factors in a
      population-based Swedish-Danish twin cohort using the co-twin control method.
      SUBJECTS AND METHODS: A questionnaire was sent to 317 twin pairs regarding
      markers of exposures in the following areas: infections/colonization and diet as
      well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were
      calculated by conditional logistic regression. When confounding appeared
      plausible, multivariate conditional logistic regression was added. The questions
      were also divided into topic groups, and adjustment was made for multiple testing
      within each of the groups. RESULTS: The response rate to the questionnaire was
      83%. In consideration of the study design, only discordant pairs were included
      (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent
      gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence
      interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for
      gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92).
      Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and
      associated with CD (OR, 2.9; 95% CI, 1.2-7.1). CONCLUSIONS: The observed
      associations indicate that markers of possible infectious events may influence
      the risk of IBD. Some of these effects might be mediated by long-term changes in
      gut flora or alterations in reactivity to the flora. The influence of smoking in
      IBD was confirmed.

PMID- 17012963
TI  - Share and share alike? Twins and environmental risk factors for inflammatory
      bowel disease.

PMID- 17012964
TI  - High incidence of Crohn's disease in Canterbury, New Zealand: results of an
      epidemiologic study.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) has increased exponentially in
      industrialized nations over the last 50 years. Previous New Zealand studies have
      shown that IBD is less common than in other countries; however, clinical
      observations suggested a high incidence and prevalence of IBD in Canterbury,
      particularly Crohn's disease (CD). AIM: This study aimed to determine the
      descriptive epidemiology of IBD in Canterbury. METHODS: Canterbury IBD patients,
      recruited using multiple strategies, gave informed consent, permission for
      clinical record review, completed a questionnaire, and were bled for DNA
      extraction as part of the Canterbury IBD Project. Cases were confirmed using
      standard criteria, and completeness of recruitment was validated using capture
      recapture methods. Demographic and phenotypic data were extracted from case
      notes. One thousand four hundred twenty patients (715 CD, 668 ulcerative colitis
      [UC]) were recruited (> 91% of Canterbury IBD patients). RESULTS: In 2004, age
      standardized (World Health Organization World Standard Population) IBD, CD, and
      UC incidence rates were 25.2, 16.5, and 7.6/100,000/year, respectively. The IBD,
      CD, and UC point prevalences on 1 June, 2005 were 308.3, 155.2, and
      145.0/100,000, respectively. CD patients were more likely than UC patients to be
      female (61.4% vs. 47.1%) and to be younger (median age, 39.9 years vs. 43.7
      years). The percent of IBD patients who were white was 97.5%. CONCLUSION: IBD is
      at least as common in Canterbury as in other western regions. CD incidence and
      prevalence are amongst the highest ever reported and are higher than for UC. IBD
      population characteristics are otherwise similar to other countries. The
      Canterbury IBD Project will be a valuable tool for future population-based IBD
      epidemiology and genetics research.

PMID- 17012965
TI  - Vicious circles in inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease can present with a bewildering array of
      disease manifestations whose overall impact on patient health is difficult to
      disentangle. The multitude of disease complications and therapeutic side effects
      result in conflicting ideas on how to best manage a patient. The aim of the study
      is to test the usefulness of influence diagrams in resolving conflicts centered
      on managing complex disease processes. METHODS: The influences of a disease
      process and the ensuing medical interventions on the health of a patient with
      inflammatory bowel disease are modeled by an influence diagram. Patient health is
      the focal point of multiple influences affecting its overall strength. Any
      downstream influence represents the focal point of other preceding upstream
      influences. The mathematics underlying the influence diagram is similar to that
      of a decision tree. Its formalism allows one to consider additive and inhibitory
      influences and include in the same analysis qualitatively different types of
      parameters, such as diagnoses, complications, side effects, and therapeutic
      outcomes. RESULTS: Three exemplary cases are presented to illustrate the
      potential use of influence diagrams. In all three case scenarios, Crohn's disease
      resulted in disease manifestations that seemingly interfered with its own
      therapy. The presence of negative feedback loops rendered the management of each
      case particularly challenging. The analyses by influence diagrams revealed subtle
      interactions among the multiple influences and their joint contributions to the
      patient's overall health that would have been difficult to appreciate by verbal
      reasoning alone. CONCLUSION: Influence diagrams represent a decision tool that is
      particularly suited to improve decision-making in inflammatory bowel disease.
      They highlight key factors of a complex disease process and help to assess their
      quantitative interactions.

PMID- 17012966
TI  - Molecular profiling of a rat model of colitis: validation of known inflammatory
      genes and identification of novel disease-associated targets.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a disease of unknown etiology
      characterized by acute and chronic relapsing inflammation. The most suitable
      animal model for studying this disease is still under debate. Microarray
      transcript profiling has the potential to illuminate the molecular processes that
      are involved in both the human condition and animal models. AIM: To identify
      differentially expressed genes in the 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      model of experimental colitis and compare gene expression profiles with that
      reported in patients. METHODS: Colitis was induced by TNBS administration (30 mg
      in 50% ethanol) in female Sprague-Dawley rats. Controls received the vehicle.
      Seventy-two hours later, the animals were killed, the colons were removed and
      scored for damage, and total RNA was isolated. Gene expression levels were
      analyzed after hybridizing experimental and control cDNA to PIQOR Toxicology Rat
      Microarrays containing 1,252 genes. Genes with 2-fold or more higher or 0.5-fold
      or less lower expression levels were selected as significantly differentially
      expressed. Results were validated using real-time reverse-transcription
      polymerase chain reaction (RT-PCR). RESULTS: We observed increased expression of
      genes that have previously been shown to be up-regulated in IBD patients,
      including chemokines/cytokines, extracellular matrix/remodeling genes,
      transcription factors and tumor necrosis factor family members. Using real-time
      RT-PCR, we validated 9 of 10 critical genes identified by DNA microarray. Fibulin
      2 and lysyl oxidase are among some of the novel genes not previously associated
      with IBD that could potentially be related to the pathogenesis of this condition.
      CONCLUSION: We provide evidence supporting the TNBS colitis model as an
      appropriate tool to study the pathology of IBD and identify molecular targets
      with clinical relevance.

PMID- 17012967
TI  - Complex insertion/deletion polymorphism in NOD1 (CARD4) is not associated with
      inflammatory bowel disease susceptibility in East Anglia panel.
AB  - BACKGROUND AND AIMS: Genetic association between inflammatory bowel disease (IBD)
      and NOD1 (CARD4) has recently been reported. This gene has structural similarity
      to NOD2 (CARD15), a confirmed susceptibility gene for Crohn"s disease (CD). The
      NOD1 association was strongest at novel complex indel ND1 + 32656. Our aim was to
      ascertain the contribution of ND1 + 32656 variants to IBD in a large independent
      United Kingdom dataset and to identify any subphenotype association within CD and
      ulcerative colitis (UC). METHODS: The presence of the ND1 + 32656 variant in our
      panel was confirmed by direct resequencing in 96 cases. One thousand three
      hundred seventy unrelated white IBD subjects (671UC, 645 CD, 54 indeterminate)
      and 760 regionally matched controls were then genotyped for the ND1 + 32656
      variant. Data were analyzed by logistic regression methods within STATA software.
      RESULTS: There was no association between ND1 + 32656 and IBD in our panel. There
      was no heterogeneity between UC and CD, nor within the CD subgroup when
      conditioned by subphenotype or the presence of NOD2 variants. CONCLUSIONS: There
      was no overall evidence of association between IBD and the reported NOD1
      susceptibility variant ND1 + 32656 in our panel. The discrepancy with the earlier
      report may reflect a smaller effect size than previously predicted, a false
      positive result in the index study, or population heterogeneity.

PMID- 17012968
TI  - Clinical guidelines for the medical management of left-sided ulcerative colitis
      and ulcerative proctitis: summary statement.
AB  - There are few published guidelines for the treatment of inflammatory bowel
      disease. Physicians choose therapy based on evidence-based data, peer and expert
      opinion, and personal experience. This article provides treatment guidelines for
      the induction and maintenance of ulcerative proctitis and left-sided colitis and
      the management of disease refractory to 5-aminosalicylic acid (5-ASA) compounds
      and corticosteroids The guidelines are derived from evidence-based data and, when
      lacking, expert opinion or the authors' experience. The comprehensive review of
      the literature is presented in the accompanying article, "The Medical Management
      of Left-Sided Ulcerative Colitis and Ulcerative Proctitis: Critical Evaluation of
      Therapeutic Trials". Rectally administered 5-ASA and corticosteroid suppositories
      are effective treatment for most ulcerative proctitis patients. Corticosteroid
      and 5-ASA enemas, which reach the splenic flexure of the colon, are recommended
      for patients with left-sided ulcerative colitis. The combination of rectally
      administered 5-ASA enemas and oral 5-ASA agents may afford better treatment of
      left-sided colitis and possibly prevent proximal extension of disease. Patients
      refractory to 5-ASAs and corticosteroids may require an immunomodulator or
      biological response modifier therapy. Those who have ongoing signs and symptoms
      of ulcerative proctitis and left-sided ulcerative colitis despite maximal medical
      therapy require a proctocolectomy.

PMID- 17012969
TI  - Medical management of left-sided ulcerative colitis and ulcerative proctitis:
      critical evaluation of therapeutic trials.
AB  - BACKGROUND: The goal of this work was to critically evaluate the published
      studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative
      colitis (L-UC). The results of this review provided the content for the
      accompanying treatment guidelines, Clinical Guidelines for the Medical Management
      of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement.
      METHODS: All English language articles published between 1995 and September 2005
      were identified through a comprehensive literature search using OVID and PubMed.
      The quality of the data supporting or rejecting the use of specific therapies was
      categorized by a data quality grading scale. An "A+" grade was assigned to
      treatment supported by multiple high-quality randomized controlled trials with
      consistent results, whereas a "D" grade was given to therapy supported only by
      expert opinion. The therapeutic efficacy of a treatment was defined by its
      success in treating UP and L-UC compared with placebo. A medication was ranked as
      "excellent" if it was specifically studied for UP and L-UC and had consistently
      positive results compared with placebo or another agent. Quality and efficacy
      scores were agreed on by author consensus. RESULTS: For the acute treatment of UP
      or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either
      alone or in combination with oral 5-ASAs, are the most effective therapy:
      evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA
      received an A+/excellent rating for maintenance of remission. Infliximab received
      an A+ grade for induction and maintenance of remission but only a "good" rating
      because the studies were performed in all UC, not specifically UP or L-UC.
      CONCLUSIONS: This critical evaluation of treatment provides a "report card" on
      medications available for the management of patients with UP and L-UC. The
      guidelines should provide a useful reference and supplement for physicians
      treating UC patients.

PMID- 17012970
TI  - Critical appraisal of the current practice in murine TNBS-induced colitis.
AB  - There is no standard practice in the induction of colitis by 2,4,6
      trinitrobenzene sulfonic acid. In this review the current practice in 2,4,6
      trinitrobenzene sulfonic acid colitis is studied using 20 recently published
      articles. We compare the different protocols, discuss the mechanism of disease
      and give recommendations for the future use of the model.

PMID- 17012971
TI  - Mycobacteria in Crohn's disease: a persistent hypothesis.
AB  - Efforts to explore a mycobacterial origin for Crohn's disease typically have
      involved an epidemiological approach, searching for Mycobacterium avium subsp.
      paratuberculosis in patient tissue. An alternative approach involves
      consideration of genetic and experimental data regarding host resistance to
      mycobacteria. From human and mycobacterial genetics, it is known that
      mycobacterial diseases depend on both pathogen and host factors and that
      tuberculosis and leprosy are effectively genetic diseases. The discovery of a
      number of Crohn's susceptibility genes, including NOD2/CARD15, demonstrates that
      Crohn's also is a complex genetic disease. Mutations in NOD2/CARD15 do not
      necessarily lead to Crohn's disease, so other mitigating factors, genetic and/or
      environmental, probably are required to produce illness. Recent work has shown
      that NOD2/CARD15 serves a role in bacterial sensing and activation of innate
      immune responses, providing a link between Crohn's genetics and an environmental
      factor, potentially a bacterial trigger. In this review, we discuss the current
      understanding of mycobacterial and Crohn's genetic susceptibility and review the
      evidence that NOD2/CARD15 may mediate host resistance to mycobacterial infection.

PMID- 17012972
TI  - Reversible myocardial ischemia during Crohn's disease exacerbation in a 17-year
      old boy.

PMID- 17012973
TI  - Association between the C3435T polymorphism of the MDR1 gene and Crohn's disease.

PMID- 17012974
TI  - Erythroderma and toxic epidermal necrolysis caused by to 5-aminosalacylic acid.

PMID- 17012975
TI  - Onset of Crohn's disease after Helicobacter pylori eradication.

PMID- 17012976
TI  - Leukocytapheresis in patients with moderate-severe steroid-dependant ulcerative
      colitis: clinical response without endoscopic response.

PMID- 17012977
TI  - Symptomatic hypokalemia associated with infliximab in a patient with Crohn's
      disease.

PMID- 17012978
TI  - Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant
      effect?
AB  - The evidence that the effects of the antidepressant duloxetine on painful
      physical symptoms in depression and chronic pain disorders are a direct analgesic
      effect rather than an indirect antidepressant effect is reviewed. Data from
      placebo-controlled acute studies of duloxetine in major depressive disorder,
      diabetic peripheral neuropathic pain and fibromyalgia syndrome are included in
      this review. In placebo-controlled studies of duloxetine in patients with major
      depressive disorder, non-depressed diabetic peripheral neuropathic pain, and
      fibromyalgia syndrome, duloxetine has a statistically significantly greater
      effect on pain than placebo. Path analysis suggests that in these patient
      populations, approximately 50, 90, and 80%, respectively, of the observed effect
      on pain is a direct analgesic effect rather than an indirect antidepressant
      effect. In fibromyalgia syndrome studies, duloxetine had similar and substantial
      effects on pain regardless of whether patients had comorbid major depressive
      disorder. Pain is a complex experience, involving both the physiological
      responses of the nociceptive system and the processing of that information in
      brain regions associated with emotion. While some effects of duloxetine on
      painful symptoms can be accounted for by its antidepressant action, the data
      strongly suggest that duloxetine also exerts a substantial direct analgesic
      effect over and above its antidepressant effects, in patients with major
      depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia
      syndrome.

PMID- 17012979
TI  - Fish oil and mental health: the role of n-3 long-chain polyunsaturated fatty
      acids in cognitive development and neurological disorders.
AB  - Epidemiological and experimental studies have indicated that consumption of more
      n-3 long-chain polyunsaturated fatty acids may reduce the risk for a variety of
      diseases, including cardiovascular, neurological and immunological disorders,
      diabetes and cancer. This article focuses on the role of marine n-3 long-chain
      polyunsaturated fatty acids in brain functions, including the development of the
      central nervous system and neurological disorders. An overview of the major
      animal studies and clinical trials is provided here, focusing on fatty acid
      supplementation during pregnancy and infancy, and prevention and management of
      Alzheimer's disease, schizophrenia, depression and attention deficit hyperactive
      disorder. Although an optimal balance in n-3/n-6 long-chain polyunsaturated fatty
      acid ratio is important for proper neurodevelopment and cognitive functions,
      results from randomized controlled trials are controversial and do not confirm
      any useful effect of supplementation on development of preterm and term infants.
      The relationship between fatty acid status and mental disorders is confirmed by
      reduced levels of n-3 long-chain polyunsaturated fatty acids in erythrocyte
      membranes of patients with central nervous system disorders. Nevertheless, there
      are very little data supporting the use of fish oil in those patients. The only
      way to verify whether n-3 long-chain polyunsaturated fatty acids are a potential
      therapeutic option in the management and prevention of mental disorders is to
      conduct a large definitive randomized controlled trials similar to those required
      for the licensing of any new pharmacological treatment.

PMID- 17012980
TI  - Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive
      compulsive disorder: a meta-analysis of randomized controlled treatment trials.
AB  - Small studies have shown positive effects from adding a variety of antipsychotic
      agents in patients with obsessive-compulsive disorder who are unresponsive to
      treatment with serotonin reuptake inhibitors. The evidence, however, is
      contradictory. This paper reports a meta-analysis of existing double-blind
      randomized placebo-controlled studies looking at the addition of the second
      generation antipsychotic quetiapine in such cases. Three studies fulfilled the
      inclusion criteria. Altogether 102 individuals were subjected to analysis using
      Review Manager (4.2.7). The results showed evidence of efficacy for adjunctive
      quetiapine (<400 mg/day) on the primary efficacy criterion, measured as changes
      from baseline in total Yale-Brown Obsessive Compulsive Scale scores (P=0.008),
      the clinical significance of which was limited by between-study heterogeneity.
      The mechanism underlying the effect may involve serotonin and/or dopamine
      neurotransmission.

PMID- 17012981
TI  - Efficacy of pharmacotherapy against core traits of borderline personality
      disorder: meta-analysis of randomized controlled trials.
AB  - We conducted a meta-analysis of published randomized, placebo-controlled clinical
      trials that evaluated the effect of pharmacotherapy in patients with borderline
      personality disorder. Comprehensive searches of the MEDLINE, EMBASE, PsychLIT and
      Cochrane Central Register of Controlled Trials databases were performed using web
      based search engines. Twenty articles, reporting 22 placebo-controlled
      comparisons, were included in the meta-analysis: eight involved antipsychotics,
      seven antidepressants and seven mood stabilizers. Antidepressants (four studies,
      standardized mean difference -0.55, 95% confidence interval -0.92, -0.17) and
      mood stabilizers (six studies, standardized mean difference -1.74, 95% confidence
      interval -2.76, -0.73) were effective against affective instability and anger,
      but did not produce significant benefits against impulsivity and aggression,
      unstable relationships, suicidality and global functioning. Antipsychotics as a
      class had a positive effect in terms of impulsivity and aggression (three
      studies, standardized mean difference -0.31, 95% confidence interval -0.63, 
      0.003), interpersonal relationships (three studies, standardized mean difference 
      0.52, 95% confidence interval -0.87, -0.17) and global functioning (seven
      studies, standardized mean difference -0.56, 95% confidence interval -1.00, 
      0.11). No difference was observed between pharmacotherapy and placebo in terms of
      participants leaving the study early. Pharmacotherapy can exert a modest
      beneficial effect on some core traits of borderline personality disorder.

PMID- 17012982
TI  - Persistence with polypharmacy and excessive dosing in patients with schizophrenia
      treated in four European countries.
AB  - The purpose of this study was to calculate the proportion of patients with
      schizophrenia receiving persistent antipsychotic polypharmacy and excessive
      dosing in four European countries; to test the hypothesis that excessive dosing
      and/or antipsychotic polypharmacy is associated with higher levels of
      psychopathology; and to establish whether use of second-generation antipsychotics
      is a protective or a risk factor for polypharmacy and excessive dosing.
      Participants with schizophrenia were recruited from patients under the care of
      psychiatric services serving geographical catchment areas in Croydon (UK), Verona
      (Italy), Amsterdam (Netherlands), and Leipzig (Germany). We defined patients
      persistently receiving high antipsychotic dose (i.e. excessive dosing) as those
      with a prescribed daily dose/defined daily dose ratio of >1.5 both at initial
      assessment and after 1 year of follow-up. Similarly, we defined patients
      persistently receiving polypharmacy as those being prescribed two or more
      antipsychotic drugs both at baseline and at follow-up. A sample of 375
      participants with schizophrenia was analyzed. A proportion of 28% of patients
      persistently received high-dose antipsychotic drugs, and a proportion of 13% of
      patients persistently received antipsychotic polypharmacy. In the multivariate
      analysis, psychopathology was not a predictor of persistent polypharmacy and
      excessive dosing; similarly, use of second-generation antipsychotics was not
      associated with polypharmacy and excessive dosing; however, persistence with high
      antipsychotic doses was predicted by baseline use of first-generation
      antipsychotics and second-generation antipsychotics concurrently. Antipsychotic
      drug use for patients with schizophrenia is only sometimes satisfactory and
      offers the opportunity of improvement. Clinicians should consider that dose
      reduction strategies have been shown to be a feasible intervention in patients
      with schizophrenia.

PMID- 17012983
TI  - Levetiracetam versus placebo in childhood and adolescent autism: a double-blind
      placebo-controlled study.
AB  - The purpose of this study was to determine the safety and efficacy of the
      anticonvulsant levetiracetam in the treatment of children with autism. A previous
      open-label study in autistic children treated with levetiracetam demonstrated
      effectiveness in hyperactivity, impulsivity/aggression, and mood lability. Twenty
      patients with autism ranging from 5 to 17 years of age were entered into a 10
      week, placebo-controlled, double-blind trial of levetiracetam versus placebo. The
      mean maximum dosage for levetiracetam was 862.50+/-279.19 mg/day. We evaluated
      global improvement of autism with the Clinical Global Impression-Improvement (CGI
      I) Scale and aggression and affective instability with the Aberrant Behavior
      Checklist (ABC) parent and teacher ratings. We measured repetitive behaviors
      using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score and
      impulsivity and hyperactivity with the Conners' Rating Scale-Revised: Long
      Version for parent and teacher. No significant difference was found between
      levetiracetam and placebo groups comparing the change in CGI-I (t=0.350,
      d.f.=13.621, P=0.765), nor on change in ABC, CY-BOCS or Conners' scales. These
      findings suggest that levetiracetam does not improve behavioral disturbances of
      autism, but are limited by the small sample size and lack of stratification of
      the autistic sample at baseline.

PMID- 17012984
TI  - Early changes of plasma lipids during treatment with atypical antipsychotics.
AB  - Metabolic side effects have been found earlier during treatment with second
      generation antipsychotics. Among those disturbances serum lipids are less
      investigated. We conducted a prospective, open study in schizophrenia patients in
      order to compare body weight and serum lipids during treatment with amisulpride,
      ziprasidone, clozapine or olanzapine over a period of 4 weeks. Body mass index,
      total cholesterol and triglycerides increased in patients treated with clozapine
      and olanzapine whereas high-density lipoprotein cholesterol decreased in those
      patients. In patients treated with amisulpride or ziprasidone, we found a
      decrease in body mass index and total cholesterol whereas high-density
      lipoprotein cholesterol increased. Our results indicate that treatment with
      ziprasidone and amisulpride is more favourable than treatment with clozapine and
      olanzapine with respect to the risk to induce weight gain and hyperlipidaemia.
      These results are important with regard to the increased risk for cardiovascular
      complications in patients with schizophrenia.

PMID- 17012985
TI  - Effect of Replens gel used with a diaphragm on tests for human papillomavirus and
      other lower genital tract infections.
AB  - OBJECTIVE: Little is known about effects of vaginal lubricants with barrier
      contraceptives on detection of sexually transmissible infections. We hypothesized
      that Replens gel used with a diaphragm would neither inhibit human papillomavirus
      (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC)
      detection in urine samples, nor affect cervical cytology quality. MATERIALS AND
      METHODS: After a clinician-collected cervical sample and a self-collected vaginal
      sample for HPV detection ("pregel" specimens), women placed a diaphragm
      containing Replens gel into the vagina. Participants (n = 77) removed the
      diaphragm after 6 hours and performed vaginal HPV self-sampling at several time
      points thereafter. Clinicians performed cervical cytology sampling and HPV
      testing ("postgel" specimens) 24 hours after diaphragm removal. Pregel and
      postgel specimens were analyzed with and without added SiHa cells (source of
      defined numbers of HPV16 genomes). HPV was detected by polymerase chain reaction
      using MY09/11 primers. Urine samples were obtained for CT and GC testing.
      Proportions of samples testing positive were compared using relative risk (RR)
      regression models. RESULTS: Proportions with detectable HPV in the clinician
      collected cervical pregel and postgel samples were not statistically different
      for samples with added SiHa cells (88.3% vs 93.2%, RR = 1.06, 95% confidence
      interval = 0.96-1.14) or for native HPV infection (32.9% vs 28.2%, RR = 0.87, 95%
      confidence interval = 0.71-1.06). In self-collected vaginal postgel samples,
      there was no trend for decreased HPV detection after gel exposure. Gel affected
      neither urine tests for CT and GC nor cytological quality. CONCLUSIONS: Recent
      Replens gel use with a diaphragm does not inhibit cervical HPV testing, urine
      testing for CT and GC, or cervical cytology quality.

PMID- 17012986
TI  - Orogenital ulceration with overlapping tuberculosis: epiphenomenon or expanding
      spectrum of Behcet disease?
AB  - Tuberculosis (TB) has rarely been reported in the context of Behcet disease. We
      present two cases of recurrent orogenital ulceration predating the onset of TB.
      No relapses of orogenital symptoms have occurred after successful TB
      chemotherapy.

PMID- 17012987
TI  - Langerhans cells in cervical intraepithelial neoplasia related to smoking habits.
AB  - OBJECTIVE: Compare the numerical densities of intraepithelial Langerhans cells of
      uterine cervix of women affected by cervical intraepithelial neoplasia grade 3
      (CIN 3) with their smoking habits. MATERIALS AND METHODS: A total of 71
      conization specimens of women affected by CIN 3 were separated in 3 groups
      according to their smoking habits (smokers, nonsmokers, and former smokers). The
      identification of the Langerhans cells was performed by immunohistochemical
      analysis using antibodies to S100 protein. The number of intraepithelial
      Langerhans cells was counted at x400 magnification under a light microscope, and
      a 10-field count was performed in areas of CIN 3 of each section. Results were
      expressed as number of cells per square millimeter of epithelium. RESULTS: There
      was no significant difference in the number of Langerhans cells per square
      millimeter of epithelium in areas affected by CIN 3 among the 3 groups (p = .5).
      There was also no significant difference in the number of cigarettes smoked per
      day (p = .09), duration of consumption (p = .34), total amount of cigarettes
      smoked during the whole life (p = .18), and duration of abstention (p = .2).
      CONCLUSIONS: It was not shown that smoking reduces the number of intraepithelial
      Langerhans cells in the cervix of women affected by CIN 3.

PMID- 17012988
TI  - Lack of agreement between cervicography and cytology and the effect of human
      papillomavirus infection and viral load.
AB  - OBJECTIVE: Cohort studies of the natural history of human papillomavirus (HPV)
      infection and cervical squamous intraepithelial lesions with repeated screening
      allow the comparison of different macroscopic and microscopic diagnostic methods.
      MATERIALS AND METHODS: Concurrent visual inspection using cervicography and
      conventional Pap cytology tests were performed during multiple visits in a cohort
      of women attending a maternal and child health clinic in Sao Paulo, Brazil. HPV
      infection status at the same visits was determined by polymerase chain reaction
      followed by typing with specific oligonucleotide probing and viral load
      quantification. Information on reproductive health and hygiene habits was also
      collected at each visit. RESULTS: Overall agreement between cervicography and
      cytology was low (kappa = 0.046), which increased only slightly when high
      oncogenic-risk HPV types (kappa = 0.120) or high viral burden (>100 copies/cell)
      (kappa = 0.170) was present. Analysis of reproductive health and hygiene habits
      revealed somewhat different risk factors for cervical lesions detected by these
      tests. However, presence of oncogenic HPV DNA (odds ratio = 36.0, 95% CI = 16.6
      77.8) and high viral burden (odds ratio = 67.34; 95% CI = 27.1-167.0) were
      strongly associated with lesions detected by cytology but not by cervicography.
      CONCLUSIONS: Although changes in the cervix (because of age, gravidity, or
      hormonal effects) may influence the performance of morphology-based screening
      tests, the lack of agreement and the different degrees of association with HPV
      infection measures indicate that a visual inspection method such as cervicography
      may detect different cervical abnormalities relative to cytology.

PMID- 17012989
TI  - Carbon dioxide laser vaporization of condyloma acuminata.
AB  - Carbon dioxide laser vaporization of condyloma acuminata continues to be the
      treatment with a greater rate of success and with excellent cosmetic results.
      OBJECTIVE: To evaluate the clinical outcome of carbon dioxide laser vaporization
      of condyloma acuminata at a referral center in Mexico. MATERIALS AND METHODS:
      Carbon dioxide laser vaporization was performed for condyloma acuminata in 46
      women and 35 men, measured from 3 to 60 months with colposcopy or peneoscopy
      every 6 months. It was a clinical prospective study. RESULTS: The average length
      of follow-up in women was 21 months, and the average length of follow-up in men
      was 16 months. The women's study follow-up showed an initial success rate of 93%,
      and the recurrence rate after 6 months of treatment was 7%. The follow-up of men
      showed an initial success rate of 69%, and the recurrence rate after 6 months was
      25%. The success rate in women after the second treatment was 100% without
      recurrence. In men, the second treatment success rate was 88%, and the recurrence
      rate after 6 months was 33%. CONCLUSIONS: Carbon dioxide laser vaporization
      condyloma acuminata provides an excellent rate of success and patient
      satisfaction.

PMID- 17012990
TI  - Unusual location of vulvar basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is a rare tumor of the vulva; it accounts
      for approximately 2% to 4% of vulvar cancer. CASE: A 73-year-old woman was
      referred because of a 2-cm ulcerative lesion on her perineum, near the anus.
      Punch biopsy showed BCC. She underwent wide local excision of tumor without any
      damage to the anal sphincter. The postoperative period was uneventful and the
      cosmetic results were good. CONCLUSIONS: BCC most commonly occurs in sun-exposed
      areas, but it may be seen in rare locations, such as in perineum. In our case,
      chronic irritation secondary to long-term chronic candidiasis in the presence of
      diabetes mellitus may have been contributory to the development of vulvar BCC.

PMID- 17012991
TI  - Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated
      factors.
AB  - OBJECTIVE: To determine the efficacy of tricyclic antidepressants (TCAs) as
      treatment for vulvodynia, and to identify demographic factors and pain
      characteristics associated with improvement. MATERIALS AND METHODS: Between
      January 2001 and April 2004, women diagnosed with vulvodynia were offered TCA
      therapy. The patients rated their worst recent pain on a 10-point scale at
      baseline and at follow-up; improvement was classified as at least 50% reduction
      in reported pain from baseline. RESULTS: Of 271 women diagnosed with vulvodynia,
      209 (77.1%) were treated initially with a TCA (amitriptyline [n = 183],
      desipramine [n = 23], and other tricyclic medications [n = 3]). One hundred sixty
      two (59.8%) of the women were followed up at a median period of 3.2 months after
      their initial visit, including 122 women who had started on a TCA. Of 83 women
      taking a TCA at the first follow-up, 49 (59.3%) improved by more than 50%,
      compared with 30 of 79 women not taking TCA at follow-up (improvement rate =
      38.0%; p =.007; odds ratio = 2.35; 95% CI = 1.23-4.42). Multivariate analysis
      indicated that age, severity of pain, diagnosis (localized vs generalized vulvar
      pain), length of time with pain before treatment, age at menarche, use of oral
      contraceptives, and the number of previous pregnancies were not associated with
      the outcome; however, taking a TCA at the time of the first follow-up was
      strongly associated with improvement (p <.001; odds ratio = 4.23; 95% CI = 1.98
      9.01). Repeated analysis including only those women prescribed with amitriptyline
      rather than any tricyclic revealed similar results. CONCLUSIONS: Women with
      vulvodynia who were prescribed a TCA in general (or amitriptyline, specifically)
      were more likely to have pain improvement compared with those women not taking
      these medications at follow-up. Randomized, controlled studies of TCAs versus
      other treatments are needed to clarify the overall effectiveness of these drugs.

PMID- 17012992
TI  - Knowledge of the cervical cancer screening process among rural and urban illinois
      women undergoing colposcopy.
AB  - OBJECTIVE: To describe knowledge of the cervical cancer prevention process among
      rural and urban women referred for evaluation of abnormal cytology. MATERIALS AND
      METHODS: Women with abnormal screening cervical cytology attending university
      colposcopy clinics (n = 178) were asked about demographic factors and knowledge
      of Pap testing, human papillomavirus (HPV) infection, and risk factors for
      cervical cancer. Responses were tabulated, and correlations assessed. RESULTS:
      Only 131 (74%) of 176 responding women understood that Pap tests evaluate the
      cervix, whereas 137 (78%) understood that Pap tests should be repeated at
      intervals of 1-3 years. The cancer screening function of a Pap test was
      identified by 122/177 (69%), but only 99 (56%) knew HPV is sexually transmitted
      and causes warts and premalignant changes. Rural residence was not associated
      with knowledge, but older women were more likely to know the nature of the Pap
      test (p =.005) and the meaning of an abnormal Pap test (p = .04). Women in higher
      income strata were more likely to understand the meaning of an abnormal Pap test
      (p = .03), the nature of HPV (p = .005), and risk factors for cervical cancer (p
      = .03). College graduates were better (p = .0005), and women of greater parity
      were less (p = .02) able than others to identify the nature of HPV, although
      neither differed from others in ability to answer other questions correctly (p >
      .1). CONCLUSIONS: Income and education are better predictors of knowledge of the
      cervical cancer prevention process than rural residence. Higher rates of cervical
      cancer in rural areas may reflect lower educational attainment and lower income.

PMID- 17012993
TI  - Early detection of cervical cancer by human papillomavirus DNA testing: case
      reports.

PMID- 17012994
TI  - Primary malignant melanoma of the uterine cervix: case report and review of the
      literature.
AB  - BACKGROUND: Malignant melanoma of the uterine cervix is a rare neoplasm with poor
      prognosis. Diagnosis is confirmed by immunohistochemical methods and by exclusion
      of other primary sites of melanoma. CASE: In this paper, we are reporting a case
      of a 38-year-old patient with a malignant melanoma of the uterine cervix.
      Diagnosis was made by histological and immunohistochemical method. The tumor was
      stage IB1 of the International Federation of Gynecology and Obstetrics
      classification. Chest x-ray and abdominopelvic computed tomography scanning were
      normal. A radical hysterectomy with bilateral salpingo-oophorectomy and pelvic
      lymphadenectomy was performed. After performing combined radical surgery and
      irradiation, complete remission of the tumor was achieved. The patient has been
      followed for 24 months. She is well without any symptoms or signs of recurrence.
      CONCLUSIONS: Malignant melanoma is usually misdiagnosed specially in the chronic
      form. The immunohistochemical study is useful for definite diagnosis. Treatment
      is not well established, and the disease histogenesis has been controversial for
      a long time.

PMID- 17012995
TI  - Postmenopausal presentation of painful vulvar vesicles and ulcers.

PMID- 17012996
TI  - Home study course: fall 2006.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his/her colposcopic skills. The
      goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to provide
      continuing medical education for physicians. The ASCCP designates this education
      activity for a maximum of 1 American Medical Association Physician's Recognition
      Award Category I Credit. Physicians should only claim credit commensurate with
      the extent of their participation in the activity. The ASCCP also designates
      their educational activity for 1 Category 1 credit hour of the ASCCP's Program
      for Continuing Professional Development. Credit is available for those who choose
      to apply. The Home Study Course is planned and produced in accordance with the
      ACCME's Essential Areas and Elements. DISCLOSURES: The clinical history and
      images in the Home Study Course may represent an actual case, but not always. To
      improve educational quality, some gross, cytological, or histological images may
      come from photographic libraries. Good teaching cases are often difficult to
      obtain, and we encourage our readers to submit cases with high-quality images to
      the Home Study Course editor or executive editor to consider for publication.

PMID- 17013049
TI  - Handoffs and transitions of care: where is the Lone Ranger's silver bullet?

PMID- 17013051
TI  - Professional diversity adds richness to the case management field.

PMID- 17013052
TI  - Evidence-based case management in a high-risk pregnancy: a case study.
AB  - This article examines the case management needs of a pregnant woman confined to
      bed after preterm premature rupture of membranes. Through the period when she is
      confined to bed, interventions and outcomes are determined on the basis of
      evidence-based guidelines. By examining this case study, it is anticipated that
      best practices can be determined for women in similar situations.

PMID- 17013054
TI  - Analyzing the value of accreditation: application of computer decision tools to a
      complex decision.
AB  - Case management organizations must often make a choice about whether to invest
      time and resources in pursuing external accreditation. The decision is a complex
      one and requires understanding of the interaction among many forward-looking
      variables. This study examines the use of computer-based tools to analyze the
      value of accreditation to support more effective decision making about whether to
      pursue accreditation.

PMID- 17013056
TI  - Disability care coordination organizations: improving health and function in
      people with disabilities.
AB  - Disability care coordination organizations (DCCOs) combine attributes of the
      medical home model and community nursing. Teams of nurses and social workers
      collaborate with the client to arrange disability-competent medical and social
      services. This article synthesizes observational findings from site visits to
      approximately half of the DCCOs operating in 2004. DCCOs have 6 core clinical
      activities: comprehensive assessment; self-directed, person-centered planning;
      health visit support; centralized medical-social record; community resource
      engagement; and constant communication. We also identified 3 core business
      competencies: service coordination, patient education/behavioral modification,
      and continuous enhancement of disability competency. Each DCCO started as a new
      company rather than as a product line of an existing business, and each included
      the target population in the design stage. Most DCCOs contract with state
      Medicaid agencies under a prepaid capitation arrangement, and some also enroll
      Medicare beneficiaries. Capitated DCCOs retain cost savings and may be
      financially stronger than fee-for-service DCCOs. Although studies suggest that
      DCCOs improve coordination and clinical outcomes while reducing costs, the
      current evidence has not been peer reviewed.

PMID- 17013057
TI  - Development of an interdisciplinary case management program for combat veterans.
AB  - The terrorist attack on September 11, 2001, prompted a major mobilization of
      Alabama active military reservists and Alabama National Guardsmen to serve in the
      Middle East. Health problems related to geographic relocation, environmental
      threats, combat and other traumatic events, and the stress associated with
      serving in an active capacity have resulted in an increase in the number of
      patients and the variety of illnesses being seen at Department of Veterans
      Affairs Medical Centers. The Tuscaloosa Veterans Affairs Medical Center developed
      a combat veterans care coordination program to efficiently and effectively manage
      the care of returning combat veterans. The development and first-year outcomes of
      the program are described.

PMID- 17013059
TI  - Drive further gains in workforce productivity through return to work strategy.

PMID- 17013058
TI  - What to look for when referring to an obesity management program.

PMID- 17013061
TI  - Considerations for the use of botulinum toxin in pain management.

PMID- 17013062
TI  - Advancements in prosthetic technology provide more options to amputees.

PMID- 17013064
TI  - Are attorneys responsible for rising healthcare malpractice costs? Pro.

PMID- 17013065
TI  - Are attorneys responsible for rising healthcare malpractice costs? Con.

PMID- 17013066
TI  - Nursing implications of the 2006 NIH State of the Science Conference Statement:
      Cesarean Delivery on Maternal Request.
AB  - Will the nation's higher rate of cesarean deliveries (CDs) (over 29%) lead to
      increased health risks for mothers and their babies? In March 2006, a National
      Institutes of Health State of the Science Conference was convened to assess
      available research on the topic. The focus was to identify outcomes from research
      studies addressing "cesarean delivery on maternal request" (CDMR), defined as CD
      without a medical indication for either the mother or the fetus. This conference
      concluded that it is currently unknown whether CDMR is really a trend in the
      United States, or whether the emergence of this phenomenon is associated with any
      specific benefits and harms to mothers and babies. More research is needed to
      determine if a trend exists. On the basis of systematic review of studies, no
      "strong quality-evidence" was found comparing CD and normal vaginal delivery
      outcomes. Future research was recommended to develop studies for this purpose in
      areas such as placental abnormalities (placenta previa and accreta) and various
      neonatal outcomes. Research on "modifiable" factors during labor and delivery
      which might decrease maternal and neonatal complications, including the risk for
      future pelvic floor disorders, was also recommended in the 2006 Conference
      Statement.

PMID- 17013067
TI  - Capturing children's voices for quality improvement.
AB  - PURPOSE: To query children about the perceptions of their inpatient healthcare
      experiences in order to improve care to make it more developmentally appropriate
      and responsive to children's needs and desires. STUDY DESIGN AND METHODS:
      Children (n = 120) were interviewed and their comments were recorded as they
      described the best and worst things about their hospitalization and made
      recommendations for change. They were approached at the time of discharge from a
      tertiary care unit. Content analysis was used to compare their responses within
      their developmental levels. Themes were developed, and data were co-coded for
      trustworthiness of findings. Quotes were extracted that illustrated the themes.
      RESULTS: Children provided insightful and specific data regarding the perceptions
      of their hospital experiences. Pain and discomfort were cited most frequently as
      the worst aspects of hospitalization and the areas most needing improvement. Play
      activities were valued by children of all ages. Their positive relationships with
      hospital staff were described frequently. The developmental stage of children
      determined the specificity and diversity of their comments. CLINICAL
      IMPLICATIONS: Children's unique perspectives should be sought regularly and their
      data included in ongoing programs of quality assessment. When only parents are
      queried, important and insightful perspectives of children are missed that could
      improve care quality.

PMID- 17013069
TI  - Proposed guidelines for skin-to-skin treatment of neonatal hypothermia.
AB  - Hypothermia is not uncommon in full-term, low-risk newborns during the first days
      of life. Standard care for treating hypothermia often involves the separation of
      the mother and the newborn while the infant is placed under a warmer and observed
      in the nursery. Because one important role of the postpartum nurse is to promote
      mother-infant attachment by encouraging the mother to spend time "getting to
      know" her infant, this separation can be problematic. This article proposes that
      skin-to-skin (STS) care, also called kangaroo care, an intervention in which the
      unclothed, diapered infant is placed on the mother's bare chest, be used to
      promote thermoregulation instead of using separation and a warmer. STS care has
      been recognized as a way to facilitate maternal-infant attachment and promote
      thermoregulation. The literature review here provides an analysis of the
      available evidence and the author's conclusion that the research supports the use
      of STS care as an alternative to traditional rewarming. The evidence was graded
      and organized into an evidence-based practice guideline for the use of STS care
      in the treatment of mild hypothermia in the low-risk infant. Suggestions for
      further research and outcomes measurement are included.

PMID- 17013071
TI  - Every labor is unique: but "call when your contractions are 3 minutes apart".
AB  - PURPOSE: To explore women's perceptions of transitioning to the birth facility
      when in labor. DESIGN: Qualitative. METHODS: Twenty-four nulliparous women were
      interviewed following their birth experiences. RESULTS: Pain was identified as
      the primary reason for transitioning to the hospital. Once arriving at the
      hospital, women often felt pressure to "get it right" and not make multiple
      trips. Three themes were identified: (a) Don't trust your body, trust us; (b)
      This is not right; and (c) This is too labor! CLINICAL IMPLICATIONS: The
      implications for nursing involve increased recognition of the range of normal
      experiences and acknowledgment that pain is a primary basis for women coming to
      the hospital as opposed to cervical dilation. Reevaluating the instruction the
      healthcare providers give to women is warranted.

PMID- 17013072
TI  - Developing a worksite lactation program.
AB  - This article describes the literature about worksite lactation programs and how
      such a service might be established to enhance breastfeeding success and lead to
      healthful outcomes for the mother and the baby. Because studies have demonstrated
      consistently that breastfeeding is associated with lower rates of infant illness,
      and that full-time maternal employment decreases breastfeeding duration,
      establishing an onsite lactation program within a corporation or organization
      could assist employees in maintaining ideal nutrition for their infants. Net
      gains for the organization, such as decreased absenteeism and fewer healthcare
      benefit claims can occur. The author suggests that the establishment of such a
      program by a nurse can be a successful nursing intervention.

PMID- 17013073
TI  - Promoting exclusive breastfeeding for Hispanic women.
AB  - This article focuses on assisting nurses with the promotion of exclusive
      breastfeeding in Hispanic women through the understanding of their heritage,
      cultural traditions, and acculturation. Nurses can incorporate these traditions
      into daily nursing practice in order to enhance the breastfeeding experience of
      Hispanic mothers. Because exclusive breastfeeding is low in minority groups in
      the United States, it is essential that nurses use the initial postpartum period
      to help educate women about exclusive breastfeeding. In order to accomplish this,
      nurses need culturally specific information, which promotes cultural traditions
      and also encourages breastfeeding.

PMID- 17013074
TI  - Lessons learned in translating research evidence on early intervention programs
      into clinical care.
AB  - There is research evidence describing quality early intervention programs that
      can promote positive child health and behavior and enhance parenting behaviors
      and parent-child interactions. Two of the programs with persuasive research
      evidence are home visitation and parent training. Despite the evidence, it seems
      that few of these strategies have been translated to real-world clinical
      settings. This article reviews an evidence-based practice framework that
      highlights the influence of the research evidence, patient preferences, provider
      expertise, setting-specific contextual factors, and important role of a
      facilitator. Examples from one particular early intervention project that
      implemented a standardized parent training program via home visiting the families
      of 2- to 6-year-old children help explicate the facilitators and pitfalls in
      translating best practices into the real-world settings. Strategies that can lead
      to successful implementation of early intervention child health and parenting
      best practices in real-world clinical settings are recommended.

PMID- 17013075
TI  - More on introducing solids.

PMID- 17013076
TI  - School nursing and Telehealth.

PMID- 17013077
TI  - Being only one and making a difference. Interview by Lynn Clark Callister.

PMID- 17013084
TI  - Minimizing risk of magnesium sulfate overdose in obstetrics.

PMID- 17013085
TI  - Anticytotoxic T lymphocyte-associated antigen 4 treatment--can melanoma be cured
      at the expense of autoimmune disorders?

PMID- 17013086
TI  - The clinical utility of cytotoxic T lymphocyte antigen 4 abrogation by human
      antibodies.
AB  - The recent cloning and identification of a variety of regulatory and counter
      regulatory molecules on T cells and antigen presenting cells has led to the
      development of antibodies and other molecules that either stimulate or abrogate
      these immune functions. Patients with autoimmune disease, graft rejection and
      cancer might benefit from the ability to manipulate immune regulatory pathways.
      The first demonstration of clinical benefit by modulation of immune regulation in
      cancer involves the use of human antibodies against cytotoxic T lymphocyte
      antigen 4. Murine preclinical studies suggested that cytotoxic T lymphocyte
      antigen-4 abrogation would provide clinical benefit after an antitumor
      vaccination. Early trials of this antibody in patients with melanoma have shown
      antitumor activity with and without vaccines that is associated with a state of
      autoimmunity. Surprisingly, the reversal of the state of autoimmunity induced by
      cytotoxic T lymphocyte antigen 4 antibodies by the use of corticosteroids does
      not eliminate clinical benefit.

PMID- 17013087
TI  - Contact stimulation of fibroblasts for tenascin production by melanoma cells.
AB  - Tenascin, an extracellular matrix glycoprotein, is widely expressed in the stroma
      of almost all types of solid tumours including malignant melanomas. On the basis
      of its antiadhesive character, it has been supposed that tenascin accumulation
      facilitates tumour cell invasion and consequent metastasis formation. We aimed to
      investigate the mechanism by which melanoma cells can modulate the production of
      tenascin by host stromal cells. The expression of tenascin in cocultures of
      fibroblasts and five melanoma cell lines, as well as in fibroblast monocultures
      treated with melanoma conditioned media, was analysed by immunofluorescent
      staining and image analysis. Tenascin production could not be observed in control
      fibroblasts or in melanoma cell monocultures. Faint labelling for tenascin could
      be detected in fibroblast monocultures treated with melanoma cell conditioned
      media while a very intense staining for tenascin could be seen in melanoma cell
      fibroblast cocultures. The tenascin staining in the cocultures was associated
      with the fibroblasts that were in close contact with melanoma cells. The level of
      tenascin production around the fibroblasts in different areas of the cocultures
      correlated well with the density of melanoma cells. Our results indicate that
      tenascin production of fibroblasts in the tumour stroma is directly modulated by
      melanoma cells mainly through cell-to-cell contact signalling.

PMID- 17013088
TI  - Restoration of E-cadherin sensitizes human melanoma cells for apoptosis.
AB  - Cell-cell adhesion is considered to be important in the development and
      maintenance of organ tissue. The spatial association between melanocytes and
      keratinocytes within human epidermis is achieved by homophilic interaction of E
      cadherin molecules located on adjacent cells. In contrast, downregulation of E
      cadherin expression in melanoma cells is considered as a key event in metastasis.
      Besides the adhesive properties, E-cadherin serves as a signal receptor linking
      to the cadherin-catenin signaling complex. As cadherins act as negative
      regulators of beta-catenin, a contribution to tumor formation seems likely. In
      the present study, it was tested whether ectopic expression of E-cadherin
      triggers apoptosis in human melanoma cell lines (G-361, JPC-298, SK-Mel-13). It
      was found that restoration of E-cadherin caused sensitization against drug
      induced apoptosis. Particularly, the release of mitochondrial cytochrome c was
      increased in response to staurosporine. Moreover, activation of caspase-3 and
      caspase-8 was elevated. Similarly, DNA fragmentation, serving as a marker for
      advanced apoptosis, was amplified in cells transduced with E-cadherin.
      Interestingly, transduction with an E-cadherin construct lacking the
      extracellular domain showed no modified apoptosis. In conclusion, our findings
      suggest therapeutic strategies that enable expression of E-cadherin in order to
      sensitize human melanoma cells towards apoptosis.

PMID- 17013089
TI  - Circulating serum levels of angiogenic factors and vascular endothelial growth
      factor receptors 1 and 2 in melanoma patients.
AB  - Angiogenesis is essential for tumor progression and metastasis; however, the
      angiogenesis regulators that are biologically relevant for melanoma are still
      unknown. In this study, we analyzed the circulating serum levels of potent
      angiogenic factors, including vascular endothelial growth factor (VEGF),
      angiogenin, transforming growth factor-beta1 and VEGF receptors, VEGFR1 and
      VEGFR2, in human melanoma patients. One hundred and fourteen patients with
      histopathologically verified cutaneous melanoma at different stages and 30
      healthy controls were investigated. Serum levels of angiogenic factors and VEGF
      receptors were quantitatively analyzed by solid-phase enzyme-linked immunosorbent
      assay. The age of the patients (61 men and 53 women) ranged from 18 to 80 years;
      median age was 51 years. Serum transforming growth factor-beta1 (P < 0.001), VEGF
      (P = 0.006) and VEGFR1 (P = 0.007) levels were significantly higher in patients
      with melanoma than in the control group. No significant differences, however,
      exist in the serum angiogenin and VEGFR2 levels between melanoma patients and the
      controls. The positive correlations of elevated serum levels of transforming
      growth factor-beta1, VEGF and VEGFR1 with advanced stages of disease were found.
      Significant relationship was found only between serum levels of VEGF and VEGFR2.
      Elevated serum transforming growth factor-beta1 (P < 0.001) and VEGF levels (P =
      0.0012) were found to be poor prognostic factors. Serum level of angiogenin and
      VEGF receptors, however, had no effect on survival. Our data suggest that the
      angiogenic serum factors, including VEGF, transforming growth factor-beta1 and
      VEGFR1, but not angiogenin and VEGFR2 were increased in melanoma patients,
      especially associated with advanced disease stages. The mechanism of VEGF
      regulation of angiogenesis may in part be due to enhanced proliferation of
      VEGFRs, especially VEGFR1.

PMID- 17013090
TI  - Frequency of colour vision deficiencies in melanoma patients: results of a
      prospective comparative screening study with the Farnsworth panel D 15 test
      including 300 melanoma patients and 100 healthy controls.
AB  - Patients with melanoma may experience a variety of different vision symptoms, in
      part associated with melanoma-associated retinopathy. For several melanoma
      patients with or without melanoma-associated retinopathy, colour vision
      deficiencies, especially involving the tritan system, have been reported. The
      frequency of colour vision deficiencies in a larger cohort of melanoma patients
      has not yet been investigated. The aim of this study was to investigate the
      frequency of colour vision deficiencies in melanoma patients subject to stage of
      disease, prognostic factors such as tumour thickness or Clark level, S100-beta
      and predisposing diseases that may have an impact on colour vision (hypertension,
      diabetes mellitus, glaucoma or cataract). Three hundred melanoma patients in
      different tumour stages and 100 healthy age-matched and sex-matched controls were
      examined with the saturated Farnsworth panel D 15 test. Seventy out of 300
      (23.3%) melanoma patients and 12/100 (12%) controls showed pathologic results in
      colour testing. This discrepancy was significant (P < 0.016; odds ratio = 2.23,
      95% confidence interval 1.15-4.32). Increasing age was identified as a highly
      significant (P = 0.0005) risk factor for blue vision deficiency. Adjusting for
      the age and predisposing diseases, we could show that melanoma was associated
      with the risk of blue vision deficiency. The frequency of blue vision deficiency
      in 52/260 melanoma patients without predisposing diseases (20%) compared with
      4/78 controls without predisposing diseases (5.1%) differed significantly (odds
      ratio 4.441; confidence interval 1.54-12.62; P < 0.004). In 260 melanoma patients
      without predisposing diseases, blue vision deficiency, as graded on a 6-point
      scale, showed a weak positive correlation (Spearman) with tumour stage (r =
      0.147; P < 0.01), tumour thickness (r = 0.10; P = 0.0035), Clark level (r = 0.12;
      P = 0.04) and a weak negative correlation with time since initial diagnosis (r = 
      0.11; P = 0.0455). Blue vision deficiency is associated with melanoma, but is
      only weakly related to stage of disease. Although we saw a positive correlation
      with well-known prognostic markers, such as tumour thickness and Clark level,
      blue vision deficiency as assessed by the Farnsworth panel D 15 test in general
      is inappropriate as a marker of tumour progression. For the use of blue vision
      deficiency in melanoma patients without predisposing diseases, a diligent test
      performance and interpretation is very important.

PMID- 17013091
TI  - Sentinel lymph node biopsy: A new perspective in head and neck mucosal melanoma?
AB  - Sentinel lymph node biopsy in patients with head and neck mucosal melanomas has
      not been performed so far. Therefore, this method as a staging tool was tested in
      a pilot study. In two consecutive patients, a lymphoscintigraphy, elective neck
      dissection with radio-guided sentinel lymph node identification, and resection of
      the primary were performed. The histopathological status of the sentinel lymph
      node was compared with the lymphadenectomy specimen and with the clinical course.
      Patient no. 1, in whom both the sentinel lymph node and the lymphadenectomy
      specimen were found to be free of tumour, is well and with no evidence of
      disease, the follow-up interval being 19 months. Patient no. 2, with the sentinel
      lymph node and remaining lymphatic basin being positive and negative,
      respectively, developed hematogenous dissemination 3 months after the primary
      treatment, and he was started on palliative chemotherapy. In mucosal melanoma,
      the prognostic significance of clinical nodal status is controversial, resulting
      in the lack of an official, applicable TNM classification and also of therapeutic
      guidelines. The presence of microscopic metastatic focus in the sentinel lymph
      node was associated with an early hematogenous dissemination. Therefore, sentinel
      lymph node biopsy, which represents a potentially efficient staging tool,
      warrants further investigation.

PMID- 17013092
TI  - Prognostic variables and prognostic groups for malignant melanoma. The
      information from Cox and Classification And Regression Trees analysis: an Italian
      population-based study.
AB  - The common way to analyse the prognostic role of selected variables in cutaneous
      melanoma patients is by means of Cox proportional hazard model. The prognostic
      effect of the simultaneous presence of more than one independent variable in the
      same patient is, however, difficult to establish. This hampers the possibility of
      tailoring a survival expectance for a selected patient as well as to communicate
      it to the patient himself/herself. The objectives of the study were to compare
      information on cutaneous melanoma prognosis from multivariate Cox proportional
      hazard model and from Classification And Regression Trees analysis.
      Classification And Regression Trees analysis is an automatic method that splits
      data by means of a binary recursive process creating a 'tree' of groups with
      different profiles according to the analysed outcome, for example, the risk of
      death. This approach automatically produces data that is easily interpreted by
      clinicians. A total of 1403 invasive cutaneous melanoma patients, 1110 from the
      Tuscan Cancer Registry and 293 from the Reggio Emilia Cancer Registry, Italy,
      were included. Cases were incident during 1996-2001 and followed up at the end of
      2003. Cox proportional hazard model and Classification And Regression Trees
      analysis were applied to the following variables: age, sex, Breslow thickness,
      Clark level, registry, subsite and morphologic type. The Classification And
      Regression Trees analysis identified 10 categories with statistically different
      survival; this results were summarized into six classes of different risks based
      on Breslow thickness, age and sex. The best prognostic group (5-year observed
      survival, 98.1%) included those subjected with Breslow less than 0.94 mm and age
      19-44 years. The same thickness but an older age (50-69 years) was associated
      with a statistically significant different prognosis (5-year observed survival,
      92.8%). The Cox proportional hazard model found sex, age, Breslow thickness,
      Clark and morphologic type to have a significant independent prognostic value. In
      conclusion, compared with the conventional approach based on Cox hazard model,
      Classification And Regression Trees analysis produces data closer to the clinical
      need of defining the prognostic profile of a specific patient. This may help the
      clinician both in the communication of risk and in the follow-up strategy.

PMID- 17013093
TI  - Cyclin-dependent kinase 2 expression in human melanomas and benign melanocytic
      skin lesions.
AB  - Cyclin-dependent kinase 2 (CDK-2) is strongly involved in regulating the
      progression of the cell cycle through G1/S checkpoint and S phase. Numerous
      studies demonstrated increased levels of CDK-2 (and also of its regulatory
      cyclins E and/or A) in different types of human tumours. Correlations found
      between the expression of those cell cycle regulators and progression and/or
      invasiveness of some tumours indicated the importance of CDK-2 as a potential
      prognostic marker. At the same time, in vitro studies of melanoma cell lines
      revealed melanocyte-specific regulation of CDK-2. The present study was aimed at
      examining levels of CDK-2 in human melanomas and benign pigmented lesions to
      evaluate whether it might be considered a potential molecular marker of melanoma
      progression. Expression of CDK-2 was determined immunohistochemically in formalin
      fixed paraffin-embedded specimens comprising 76 lesions including 41 primary
      cutaneous melanomas, 15 lymph node melanoma metastases (in eight cases correlated
      with primary tumours), three melanoma recurrences (two cases correlated with both
      primary and metastatic melanomas) and 17 nevi. Our results demonstrate that
      development and progression of melanoma are associated with changes in CDK-2
      expression level. Statistical significance of the observed correlations indicates
      that CDK-2 may be a suitable prognostic marker for melanoma and perhaps also a
      target for chemotherapeutic drugs.

PMID- 17013094
TI  - Autotaxin stimulates urokinase-type plasminogen activator expression through
      phosphoinositide 3-kinase-Akt-nuclear [corrected] factor kappa B signaling
      cascade in human melanoma cells.
AB  - Autotaxin, a lysophospholipase D producing lysophosphatidic acid, augments
      invasive and metastatic potential of tumor cells. Current investigations have
      focused on understanding the molecular mechanisms by which autotaxin regulates
      the expression of a major mediator of tumor invasion and metastasis, urokinase
      type plasminogen activator (uPA) in human A2058 melanoma cells. Autotaxin induced
      uPA expression in a dose-dependent manner that was inhibited by pharmacological
      inhibitors for Gi (pertussis toxin), phosphoinositide 3-kinase (PI3K, LY294002),
      Akt inhibitor (AktI), proteosome activity and IkappaB phosphorylation
      (pyrrolidine dithiocarbamate), and by a dominant negative mutant (DN) of Akt.
      Autotaxin phosphorylated Akt and induced the translocation of nuclear [corrected]
      factor-kappaB (NF-kappaB) to the nucleus that were inhibited by AktI or by
      overexpressing DN-Akt. Consistently, green fluorescence protein-tagged p65 of NF
      kappaB accumulated in the nucleus by autotaxin that was abrogated when the cells
      were transfected with DN-Akt. Moreover, autotaxin increased the DNA binding
      ability of NF-kappaB and promoter activity of uPA. Collectively, these data
      strongly suggest autotaxin induces uPA expression via the Gi-PI3K-Akt-NF-kappaB
      signaling pathway that might be critical for autotaxin-induced tumor cell
      invasion and metastasis.

PMID- 17013095
TI  - Proliferating endothelial cells, but not microvessel density, are a prognostic
      parameter in human cutaneous melanoma.
AB  - The induction of angiogenesis is crucial in the development of most human tumors.
      Angiogenesis is routinely assessed by the density of tumor microvessels. This
      technique reveals controversial results on the clinical and prognostic value of
      angiogenesis in melanoma. We investigated angiogenesis in tumor tissues of 58
      cutaneous melanoma patients, of which a clinical follow-up of over 10 years was
      available, through assessment of microvessel density and by enumeration of the
      number of proliferating endothelial cells. To that end, vessels were
      immunohistochemically detected by CD31/CD34 staining, and proliferating
      endothelial cells were enumerated in a double staining with the proliferation
      marker Ki67. We found that microvessel density did not correlate with tumor stage
      or survival, neither in intratumoral nor in peritumoral areas. In contrast,
      proliferating endothelial cells were only observed in intratumoral areas and were
      correlated positively with tumor stage and the presence of distant metastases. In
      addition, a strong positive correlation was found with the number of
      proliferating tumor cells. Finally, high numbers of growing endothelial cells
      predicted short survival. Our results show that angiogenesis could best be
      measured by enumeration of proliferating endothelial cells and that this
      parameter has prognostic value in patients with cutaneous melanoma.

PMID- 17013096
TI  - Pseudomelanoma after Solcoderm treatment.
AB  - We describe a case of pseudomelanoma after Solcoderm treatment. Pseudomelanoma is
      a pathological entity describing the histological findings in cases of
      recurrences of a partially excised melanocytic nevus, resembling melanoma.
      Solcoderm is an aqueous solution containing organic and inorganic acids that
      destroys a lesion by tissue mummification. It has been used for the treatment of
      benign skin lesions. Appearance of pseudomelanoma after Solcoderm treatment
      stressed the controversy of the use of Solcoderm in pigmentary lesions, and that
      surgical removal is preferred in cases of pigmented nevi.

PMID- 17013097
TI  - High flotillin-2 expression is associated with lymph node metastasis and Breslow
      depth in melanoma.

PMID- 17013099
TI  - Simultaneous appearance of acute myeloid leukemia in a patient with bilateral
      primary uveal melanoma.
AB  - We report a rare case of a patient with bilateral uveal melanoma (the first eye
      surgically treated 6 years before the occurrence of melanoma in the contralateral
      eye), who developed an acute myeloid leukaemia.

PMID- 17013098
TI  - Cyclooxygenase-2 inhibition and regression of metastatic melanoma.

PMID- 17013198
TI  - Cardiac surgery without the use of cardiopulmonary bypass: the challenges.
AB  - Minimally invasive bypass grafting of the internal thoracic artery to the left
      anterior descending artery has become routine in many institutions. Currently,
      indications for single vessel revascularization are expanding to those patients
      not suitable to be operated upon using extracorporeal circulation, but surgeons
      remain rather reluctant when multivessel disease is concerned. In such cases, the
      'hybrid technique', i.e. single vessel bypass grafting followed by percutaneous
      transluminal coronary angioplasty at a different site, seems to be a more
      appropriate alternative. Despite the merits of minimally invasive surgery, the
      majority of surgeons do not believe that it is possible to achieve the same
      quality of anastomosis on a beating heart as on an arrested heart.

PMID- 17013199
TI  - Renal preservation in cardiac surgery.
AB  - There is no conclusive evidence that any pharmacological intervention is able to
      offer effective protection for the kidneys during cardiac surgery. More research
      is needed into the underlying mechanisms of postoperative renal failure,
      specifically with regard to the possible role played by endothelial factors and
      inflammatory response.

PMID- 17013200
TI  - The balance of pro- and anti-inflammatory cytokines in cardiac surgery.
AB  - Homeostatic control of the balance of pro- and anti-inflammatory cytokines is
      important for the maintenance of health. Cardiac surgery, with its intense pro
      inflammatory stimulus, constitutes a major challenge to the patient's ability to
      maintain this balance. Pre- and intraoperative factors influencing the
      maintenance of cytokine balance are discussed.

PMID- 17013201
TI  - Peripheral vascular surgery: does anesthetic management affect outcome?
AB  - Several recent articles have examined the effect of anesthetic technique on
      outcome in patients undergoing peripheral vascular surgery. This review examines
      the recent literature and evaluates the role of new data in advancing current
      understanding of the impact of anesthetic management on outcome in this high-risk
      population.

PMID- 17013202
TI  - Perioperative hypertension: new strategies for management.
AB  - Perioperative hypertension is a very frequent occurrence and requires the
      anaesthetist to make clinical decisions regarding antihypertensive therapy,
      evaluation of risk, cancellation of surgery and treatment of high and low blood
      pressure. Perioperative management of hypertensive patients must take into
      account the possible consequences of left ventricular diastolic dysfunction and
      reduced coronary reserve.

PMID- 17013203
TI  - Stress failure of the blood-gas barrier.
AB  - The blood-gas barrier must be extremely thin because oxygen and carbon dioxide
      cross the alveolar-capillary membrane by passive diffusion, and the diffusion
      resistance is proportional to thickness. Despite its remarkable size (harmonic
      mean thickness approximately 0.6 microm) the membrane must be immensely strong,
      because maintenance of its integrity is fundamental for pulmonary gas exchange.
      The basement membrane is probably the principal anatomical structure providing
      the strength of the blood-gas barrier. Experimental studies have demonstrated
      that wall stress of the capillaries can become very high when perfusion pressure
      is increased to 5.2 kPa (39 mmHg) or more, which was associated with breaks of
      the capillary endothelium, the alveolar epithelium, or both. These values are
      potentially reached or exceeded in different cardiac or pulmonary diseases, or in
      healthy humans subjected to heavy exercise. Stress failure of pulmonary
      capillaries may play a role in neurogenic pulmonary oedema, high-altitude
      pulmonary oedema, re-expansion pulmonary oedema, and some forms of the adult
      respiratory distress syndrome. Increased alveolar pressure due to lung inflation
      potentiates damage of the blood-gas barrier, suggesting that increases in
      capillary transmural pressure and transpulmonary pressure are equivalent in terms
      of their effects on capillary wall stress. These data may have importance for the
      management of patients with acute respiratory failure requiring mechanical
      ventilation.

PMID- 17013204
TI  - Anaesthesia for lung volume reduction surgery.
AB  - To date, only a few published studies have been concerned with the
      anaesthesiological aspects of lung volume reduction surgery. This review
      summarizes the different anaesthetic concepts and offers a general strategy to
      meet specific requirements. Limitation of peak inspiratory pressure, tolerance of
      hypercapnia and avoidance of hypoxia during one-lung ventilation, and the
      immediate postoperative tracheal extubation of these patients, are considered to
      be crucial. However, many aspects of the procedure and of anaesthesiological
      management remain to be elucidated.

PMID- 17013205
TI  - Perioperative management of patients undergoing lung transplantation.
AB  - This review focuses on recent developments in the perioperative management of
      patients undergoing lung transplantation. Relevant current literature and the
      experience of the Munich Lung Transplant Group were taken into consideration.
      Recent advances include the use of inhalational nitric oxide for the treatment of
      early graft dysfunction and the use of aerosolized cyclosporine for the treatment
      of recurrent and steroid-resistant acute rejection. Opportunistic infections
      remain a major source of morbidity and mortality in lung transplant recipients.

PMID- 17013206
TI  - Pathophysiology of asthma.
AB  - Further insight into the inflammatory process of asthma has accumulated during
      the past few years. New inhalational anaesthetics seem to have a better
      bronchorelaxant effect, and prophylactic treatment with beta2-agonists and local
      anaesthetics may also be an alternative. Bronchospasm during anaesthesia appears
      to be less common now, but persons with asthma should still be considered to be
      at an increased risk of severe morbidity.

PMID- 17013208
TI  - Pharmacologic strategies in acute respiratory distress syndrome.
AB  - Treatment of the acute respiratory distress syndrome includes both supportive
      measures and correction of the underlying cause. Various pharmacological
      interventions have been proposed to limit the severity of lung injury and enhance
      the healing process, including exogenous surfactant, inhaled vasodilators (mainly
      nitric oxide), corticosteroids, prostaglandin E1, antioxidants (N
      acetylcysteine), ketoconazole and other substances. Some of these interventions
      are administered via the airways, for example inhaled nitric oxide or liquid
      ventilation with perfluorocarbons. Some have beneficial effects on surrogate end
      points such as pulmonary gas exchange. However, in large prospective trials none
      of these pharmacological approaches have resulted in significantly improved
      survival in acute respiratory distress syndrome patients.

PMID- 17013209
TI  - Oxygen delivery and outcome.
AB  - Perioperative haemodynamic optimization of high-risk surgical patients seems to
      be associated with a reduction in morbidity and mortality. There is, however, no
      evidence to support the use of treatment directed at achieving survivor values of
      oxygen delivery and consumption in critically ill patients after admission to
      intensive care. Mitochondrial dysfunction may be responsible for the inability of
      patients dying of sepsis to increase oxygen consumption and thus may explain why
      therapies directed at reducing mortality through increasing oxygen delivery have
      not been successful. In response to the recent controversy surrounding the risks
      versus benefits of pulmonary artery catheterization, current research is focusing
      on the development and evaluation of noninvasive methods to assess the adequacy
      of resuscitation.

PMID- 17013210
TI  - A future role for the pulmonary artery catheter?
AB  - Either a moratorium prohibiting, or a prospective, randomized clinical trial on
      pulmonary artery catheter use has been proposed. Expert opinion regarding both
      this suggestion and on the therapeutic efficacy of interventions guided by
      pulmonary artery catheters in a variety of clinical settings has included (in my
      view incorrectly) physician prerogative and perceived threats to therapeutic
      freedom. The legitimate concerns of worsened patient outcome secondary to
      pulmonary artery catheter use and demonstrably inadequate intellectual
      preparation of practitioners and allied healthcare professionals, which may
      exacerbate these deficiencies, have also been discussed. The future of the
      pulmonary artery catheter is questioned; physicians must evaluate the available
      information and, more importantly, critique their current practice, before
      employing this technology.

PMID- 17013211
TI  - Current concepts in treatment of closed head injury.
AB  - Standards for management of severe closed head injury should help to establish a
      foundation for routine care and ongoing research. Studies of cerebral blood flow,
      oxygenation and metabolism suggest a pattern seen in patients with low c?scores
      on the Glasgow Coma Scale (GCS), who are known to have poor outcomes. Moderate
      hypothermia, although improving outcome for patients with GCS of 5-7, has not
      been beneficial for patients with lower GCS scores.

PMID- 17013212
TI  - Sedation in the critically ill patient.
AB  - The goal of critical care medicine is to support organ function and maintain
      homeostasis until healing can occur. Sedation and analgesia may blunt the
      physiologic and psychologic sequelae of intensive care unit stress, and support
      homeostasis. Although a wide variety of agents have been used empirically, the
      recognition of analgesia, amnesia, and hypnosis as discrete elements comprising
      the sedated state has facilitated an individualized approach to therapy. Because
      intensive care unit patients are a highly heterogeneous population with varying
      levels of end-organ compromise, the development of specific, easily titratable,
      parenteral agents has made intensive care unit sedation safer. A trend toward
      refining dosage regimens in order to minimize the total dose of drug administered
      and to reduce the occurrence of residual sedation is driven by utilization and
      cost concerns. The capability for simple bedside electrophysiologic monitoring of
      the level of sedation is expected to improve the ability to provide optimal
      therapy.

PMID- 17013213
TI  - Resuscitation.

PMID- 17013214
TI  - State-of-the-art blood saving techniques.
AB  - Preoperative autologous donation, the use of erythropoietin, acute normovolaemic
      haemodilution, acceptance of minimal perioperative haemoglobin levels, the use of
      specific drugs (aprotinin, antifibrinolytics), cell saving and a meticulous
      surgical technique aimed at minimizing blood loss have all been described as
      blood saving techniques. Each has proved effective in reducing the need for
      allogeneic blood transfusions. With an appropriate selection of patients, all
      techniques can be used efficiently.

PMID- 17013215
TI  - Blood transfusion: influence of transfusion therapy on outcome.
AB  - Few studies have addressed the influence of different transfusion therapies on
      outcome in a convincing way. Proven adverse impact of allogeneic blood on outcome
      is minimal. Acute mortality has declined to about 1 : 500,000 and the rate of
      transfusion-transmitted infections is decreasing, too. Data on postoperative
      infections and non-Hodgkin's lymphoma as possible adverse effects are
      controversial. Evidence for an increased risk of tumour recurrences is lacking.
      Alternatives to allogeneic blood may have appreciable risks: perioperative blood
      recovery had a fatality rate of more than 1 : 40,000. Reduction of allogeneic
      blood exposure may not be equated with improved outcome.

PMID- 17013216
TI  - Fluid replacement for hypotensive injury victims: how, when and what risks?
AB  - Intravenous fluid administration is considered universally indicated for patients
      with post-traumatic hypotension of presumed hemorrhagic origin, regardless of the
      mechanism of injury, anatomic location, and whether hemostasis has been achieved.
      This premise is based primarily on animal studies in which blood loss results
      from a controlled catheter withdrawal. However, more recent hemorrhage models
      that incorporate a vascular injury, as well as recently completed clinical
      trials, have indicated that attempts to restore blood pressure before surgical
      hemostasis may have the undesirable effects of accentuating hemorrhage and
      mortality.

PMID- 17013217
TI  - Burns.
AB  - Inhalation injuries still significantly increase the morbidity and mortality of
      burn patients. Advances in ventilatory support appear to decrease the frequency
      of pneumonia and improve the survival of patients. It is now well accepted that
      early enteral feeding of patients with burn injuries is very important. The
      addition of anabolic agents in burn care and nutrition may be of importance.
      Patients receiving pre-storage filtered blood components have fewer blood
      transfusion-induced side effects and the requirement for transfusion is reduced.
      Current research on the cellular response to burn injury holds promise for
      further improvement in burn care.

PMID- 17013218
TI  - Special aspects of cardiopulmonary resuscitation: vasopressin as vasopressor,
      analysis of ventricular fibrillation waveform and tidal volume in an unintubated
      patient.
AB  - Several laboratory studies have shown that vasopressin is a promising vasopressor
      during cardiopulmonary resuscitation; clinical investigations are currently being
      performed to determine whether vasopressin is superior compared with placebo or
      adrenaline during cardiopulmonary resuscitation. Ventricular fibrillation median
      frequency, dominant frequency, edge frequency and voltage amplitude can be used
      as noninvasive tools to monitor efficacy of ongoing cardiopulmonary resuscitation
      efforts. The newly recommended lower tidal volumes of 0.5 litres instead of 0.8
      1.2 litres for ventilation of an unintubated cardiac arrest victim have been
      shown to be beneficial in mechanical models of an unprotected airway.

PMID- 17013219
TI  - Special aspects of severe head injury: recent developments.
AB  - Trauma in general, and head injury in particular, is the most frequent cause of
      mortality and morbidity in those aged up to 45 years. Outcome from severe head
      injury depends on the nature and severity of the primary lesion, and the
      manifestations of secondary brain damage of extra- and intracranial origin. The
      most important sequela is cerebral ischaemia resulting from intracranial
      hypertension caused by, for example, traumatic brain swelling or intracranial
      haemorrhage and/or systemic complications, of which arterial hypotension is the
      most significant. Because treatment so far is limited in principle to general
      symptomatic measures, continuing improvements in patient management is required
      on a comprehensive basis. In this context, major efforts are being made all over
      the world, not only to assess the current efficacy of, for example, logistics,
      organization and patient management in severe head injury, but also towards
      development of a consensus aimed at standardizing management and treatment
      procedures. With regard to the predominant influence of secondary ischaemia of
      the brain, recent experimental and clinical pathophysiological studies focus on
      the quality of cerebral blood flow, including the intriguing phenomenon of post
      traumatic vasospasm. Other research objectives are concerned with the role of
      cytokines, leucocyte-endothelial interactions and molecular genetics in severe
      head injury (e.g. illuminated by the emerging role of the apolipoprotein E gene).
      Finally, the formation of international organizations, the American and European
      Brain Injury Consortium, is noteworthy. Although their primary objective is the
      development of guidelines for clinical trials, future objectives are conceivably
      more far spread and influential. It can be hoped, therefore, that the
      unacceptably poor outcome from severe head injury until now can be improved.
      Moreover, alleged management discrepancies between up-to-date trauma centres and
      rural hospitals may be eliminated.

PMID- 17013220
TI  - On the withdrawal of consent.

PMID- 17013221
TI  - Measuring the immeasurable? Assessing the quality of anaesthetic care.
AB  - Quality can be viewed from three perspectives: the requirements of the healthcare
      system; issues related to delivery of care, such as access; and methods used to
      measure quality, such as outcome analysis. These viewpoints can be applied to the
      anaesthetic literature to analyse the assessment of quality of care.

PMID- 17013222
TI  - With what certainty can post-anaesthetic outcome be predicted?
AB  - Prediction of outcome is an important aspect of anaesthetic practice. In
      populations prediction systems are well developed, but systems capable of
      identifying individuals at risk are still lacking. Importantly, anaesthesia
      outcome cannot be considered in isolation and must include patient, surgical, and
      social factors.

PMID- 17013223
TI  - An ethical dilemma in anaesthetic practice: when the anaesthetist believes
      surgery to be futile.
AB  - In a clinical situation when the anaesthetist believes surgery to be futile, he
      or she must consider and understand the basis for that belief, whether it is a
      value judgement or an objective opinion, and know that the primary duty of care
      is to the patient.

PMID- 17013224
TI  - Fostering progress and development (in an anaesthetic department) at a time of
      cost containment.
AB  - The lessons learned in industry can be applied to anaesthetic departments.
      Progress and development are part of improving quality, and evidence is emerging
      that improved quality can reduce costs. Improving quality requires anaesthetic
      departments to develop a clear customer focus. Education, training, research and
      quality improvement are essential components of a quality anaesthetic department.
      Some of the cost reductions are achieved by development of partnerships with
      customers and suppliers. The emphasis is likely to shift from cost reduction to
      quality improvement and anaesthetic departments should anticipate this change.

PMID- 17013225
TI  - The impact of managed care on anesthesia residency training and clinical
      practice.
AB  - In this review, we attempt to summarize some of the complex issues surrounding
      managed care and discuss the resultant changes in anesthesiology practice and
      residency training in the USA. These changes have affected physician autonomy,
      job availability for graduates of residency training, and interest by medical
      students in the specialty. Anesthesiologists are focusing on increasing the value
      of the anesthesia service to patients, surgeons, hospitals, and managed care
      organizations, thereby securing the future growth of the specialty.

PMID- 17013226
TI  - Old concepts applied to new problems: the fetus as a patient.

PMID- 17013227
TI  - What's new with intrathecal narcotics for labor analgesia.
AB  - The profound analgesic properties of intrathecal narcotics without motor blockade
      make them an excellent choice for pain relief during the first stage of labor.
      Recent studies have attempted to define more clearly the pharmacology of commonly
      used agents. In this review we shall outline some of these advances and discuss
      their impact on labor.

PMID- 17013228
TI  - What's new in local anaesthetics for obstetric anaesthesia?
AB  - Despite its efficacy, bupivacaine has never been considered to be the most
      suitable agent for achieving anaesthesia and analgesia in the obstetric patient.
      Ropivacaine is less cardiotoxic than bupivacaine and, at low concentrations, can
      produce analgesia with minimal motor block, attributes which make it potentially
      very suitable for use in obstetrics. However, further research is required to
      ultimately establish ropivacaine's place in obstetric anaesthesia and analgesia.
      Levobupivacaine, the L isomer of bupivacaine, is of similar potency to
      bupivacaine but has the advantage of being significantly less cardiotoxic than
      racemic bupivacaine, which suggests that it might ultimately replace racemic
      bupivacaine in obstetric practice.

PMID- 17013229
TI  - Epidural anesthesia and the progress of labor.
AB  - Epidural block remains the most effective, safe approach to pain relief for
      labor, and demand for its use continues to grow. Opposition to epidural block in
      labor, based on a widely acclaimed 1993 study, has led to the widespread
      discouragement of its use for laboring women and the denial of payment to some
      anesthesiologists who use it. Within the past year, strong evidence has emerged
      showing that the association of epidural block with dystocia and cesarean section
      is casual and not causal.

PMID- 17013230
TI  - Does epidural analgesia during labour affect the neonate?
AB  - Focus has changed from the immediate postpartum condition to the more long-term
      outcome of the neonate with respect to the use of epidural analgesia in labour.
      Anaesthesiologists have been slow to respond to the demand for this information.
      Newer analgesic agents and techniques may offer some advantage to the neonate;
      however, extensive study is still needed.

PMID- 17013231
TI  - Antiemetics for obstetric and gynecological procedures.
AB  - Nausea and vomiting is a troublesome side-effect that occurs more frequently
      during obstetric and gynecological procedures than during most other surgical
      procedures. Recent research has focused on the efficacy and safety of new
      antiemetic medications, primarily 5-hydroxytryptamine subtype 3 receptor
      antagonists, as well as clinical comparisons of these new drugs with older,
      established antiemetics. In the current healthcare environment, the cost
      effectiveness of available antiemetic therapies has also become increasingly
      important, and this has been addressed in some of the recent literature.

PMID- 17013233
TI  - Paediatric trauma and resuscitation.
AB  - Severe paediatric trauma differs from adult trauma in that blunt trauma, and
      especially head trauma, represents 98% of cases. In these instances, early
      control of the airways, prompt haemodynamic stabilization, emergency explorations
      and further conservative management of bleeding abdominal lesions are the most
      challenging issues. On-scene resuscitation, primary stabilization before
      transportation and transfer to a specialized centre are mandatory. The pre
      hospital management of injured children, however, is frequently neglected. The
      need for emergency intubation and rapid intravenous access insertion is difficult
      to meet, in spite of many attempts to ameliorate this situation. The option of
      conservative surgical management of spleen and liver lesions has been extensively
      developed, and is now applied in many paediatric institutions with a high rate of
      success. A better application of on-scene resuscitation and of the selective
      management of bleeding lesions is the key to the prevention of secondary lesions,
      representing a major source of avoidable death and long-term sequelae.

PMID- 17013234
TI  - Pediatric solid organ transplantation.
AB  - Solid organ transplantation offers hope for long-term survival and more normal
      lifestyles for children. Many of the procedures used are scaled-down versions of
      those used in adults and are associated with distinct challenges in children.
      Recent studies have provided insights into how transplantation can best serve
      these patients.

PMID- 17013235
TI  - Paediatric pain: a year in review.
AB  - There has been a steady advance in the understanding of pain measurement,
      prevention and treatment in children, and some of the recent progress is reviewed
      here. Important new discoveries in neonatal pain and pain assessment have
      overshadowed pharmacology in the past few years, although there has been good
      progress in the use of both opioid and non-opioid medications in children. The
      question of whether preemptive analgesia exists and can be utilized practically
      in children still puzzles us, but we are beginning to understand how to approach
      the problem, at least.

PMID- 17013236
TI  - Advances in neonatal care and surgery.
AB  - Neonatology has seen many advances over the past decade. Exogenous surfactant
      therapy is now a mainstay treatment for respiratory distress syndrome. Partial
      liquid ventilation, high-frequency ventilation, and inhaled nitric oxide are all
      relatively new modalities, which have enabled neonatologists to treat with
      varying degrees of success ever younger and smaller patients. The purpose of this
      review is to examine studies regarding the long-term outcome of high-risk
      neonates, the various treatment modalities, and current neonatal surgical
      techniques, all of which will influence our care of the neonate.

PMID- 17013237
TI  - Pediatric anesthesia and recent developments in asthma in children.
AB  - Asthma is a chronic inflammatory disease and the physiological consequence is
      bronchial hyperresponsiveness to different stimuli. With the worldwide increase
      in the prevalence of asthma, an increased number of asthmatics are likely to
      require anesthesia for surgical procedures. Recent investigations described the
      role played by different environmental agents in asthma, and clarified assessment
      and management strategies which can be applied to anesthesia in order to decrease
      the morbidity related to perioperative bronchospasm in children with asthma.

PMID- 17013238
TI  - Reducing cardiovascular risk in patients undergoing non-cardiac surgery.

PMID- 17013239
TI  - Perioperative management of patients with impaired left ventricular function.
AB  - The development of acute perioperative left ventricular failure leading to
      haemodynamic catastrophe has several reasons. The management of left ventricular
      dysfunction requires a step-by-step therapeutic approach. Extensive haemodynamic
      monitoring is fundamental to distinguish between the need for positive inotropes,
      lowering pre- or afterload or increasing perfusion pressure by vasopressors.
      Catecholamines are still the cornerstone for treating acute left ventricular
      dysfunction. Whether synthetic, costly catecholamines offer any advantage over
      'natural', low-priced catecholamines has not yet been definitely determined.
      Optimizing ventricular loading by vasoactive substances will help to improve
      overall myocardial performance. Knowledge of pre-existing cardiac disease and of
      haemodynamic principles are prerequisites for selecting an appropriate
      therapeutic regime. This appears to be more important for successfully treating
      acute perioperative myocardial failure than waiting for a new 'magic' substance.

PMID- 17013240
TI  - Inhibitors of the renin angiotensin system: implications for the
      anaesthesiologist.
AB  - The major long-term benefits of angiotensin-converting enzyme (ACE) inhibitors
      have now clearly been demonstrated in patients with arterial hypertension,
      cardiac insufficiency, coronary artery disease and several renal diseases. Such
      long-term treatment markedly alters the cardiovascular response to anaesthesia
      and surgery, whereas preliminary data suggest that short-term renin angiotensin
      system blockade might provide perioperative organ protection and improved
      circulatory conditions. Besides the classic view that the conversion of
      angiotensin I to angiotensin II is mainly due to ACE, alternative pathways have
      recently been identified, including cathepsin G as well as chymostatin- and
      aprotinin-sensitive serine proteases that are released from mastocytes and
      endothelial cells and which are insensitive to the effects of ACE inhibitors.
      These proteases are thought to contribute to tissue perfusion under hypoxic
      conditions and to structural remodelling. In clinical practice, ACE inhibitors
      may be preferred to angiotensin II receptor antagonists since the former, besides
      reducing angiotensin II synthesis, also lead to an accumulation of kinins (e.g.
      bradykinin), which have important cardio- and renal protective effects through
      liberation of prostacyclin and nitric oxide in endothelial cells and through
      stimulation of guanylate cyclase to form cyclic GMP.

PMID- 17013241
TI  - Outcome after general or regional anaesthesia in high-risk patients.
AB  - This review is a critical analysis of research design for studies of outcome
      comparing epidural anaesthesia and analgesia with general anaesthesia and
      alternative postoperative analgesia regimens. If important advances in knowledge
      are to be made, appropriately designed multicentre randomized controlled trials
      are essential. These trials must incorporate strict controls on patient entry, a
      comprehensive range of carefully defined and clinically significant morbidity
      endpoints and the previous determination of sample size through a proper analysis
      of statistical power.

PMID- 17013242
TI  - Neuromuscular disorders.
AB  - Neuromuscular diseases form an heterogeneous group of illnesses. These diseases
      are rare and studies concerning their anaesthetic management are difficult.
      Patients with neuromuscular disease represent a challenge for the
      anaesthesiologist because of the frequent perioperative complications. Cardiac
      and respiratory functions are often involved, and the severity of the lesions are
      difficult to estimate. The possible interactions of different drugs necessitates
      a good knowledge of the drugs' actions and pathophysiological mechanisms.

PMID- 17013243
TI  - Anaesthesia for the allergic patient.
AB  - Knowing that allergic reactions that occur during anaesthesia are essentially
      caused by muscle relaxants or latex, the patients who should be singled out
      during the preanaesthetic visit are those already allergic or thought to be
      allergic to these two substances. On the other hand, atopy or allergy to other
      drugs, such as antibiotics, has not been proved to favour the triggering of
      anaphylactic shocks with anaesthetic drugs. Allergy to local anaesthetics is so
      exceptional that it may be easily dismissed by a challenge test.

PMID- 17013244
TI  - Renal disease and transplantation.
AB  - The nephrotoxicity of anaesthesia remains a current question with the use of low
      flow sevoflurane anaesthesia, although the issue of clinically relevant toxicity
      in patients with renal disease has not been evaluated. With regard to kidney
      transplantation, the type of fluid administered for volume management of organ
      donors appears crucial to improve postoperative recovery of renal function.

PMID- 17013246
TI  - Chirality in anaesthesia--ropivacaine, ketamine and thiopentone.
AB  - Drug chirality (molecular handedness) is a source of pharmacological differences
      between otherwise chemically identical molecules. Specific applications to the
      pharmacology of ropivacaine (single enantiomer), ketamine and thiopentone (both
      racemates) are discussed. Ropivacaine is produced as a single S-enantiomer
      homologue of the more toxic bupivacaine to preclude the higher central nervous
      system and heart toxicity found in the R-enantiomer. S-ketamine is presently
      undergoing trials as a potential replacement for the racemate, on the grounds
      that it optimizes anaesthesia and minimizes psychotomimetic phenomena.
      Thiopentone, previously known to have quantitative differences in the
      pharmacology of its enantiomers, has recently also been shown to have
      pharmacokinetic differences. The evidence for these claims is discussed in this
      review.

PMID- 17013247
TI  - Etomidate revisited.
AB  - The major advantage of etomidate is its lack of cardiovascular side effects. In
      addition, etomidate is supposed to be neuroprotective. The side effects of
      etomidate include adrenal suppression and myocloni. A review of the recent
      literature on etomidate, its clinical use, its side effects and its mechanism of
      action was performed. Among others, major recent advances include a new drug
      preparation devoid of propylene glycol and its side effects, a new pretreatment
      technique that may reduce the incidence of myocloni, and the identification of
      its site of action in the central nervous system.

PMID- 17013248
TI  - Anaesthetic organ toxicity: is it really a problem?
AB  - The hepatotoxicity of halothane is now well known, but only became apparent after
      several years of use. The nephrotoxicity of methoxyflurane was not realized
      immediately, but once identified, led to its withdrawal from use. Therefore, when
      new agents that appear to offer significant advantages over established drugs
      become available, exhaustive testing and monitoring is necessary to ensure their
      safety. Sevoflurane, recently available in the UK and the USA but used for some
      time in Japan, has been subjected to considerable scrutiny.

PMID- 17013249
TI  - Volatile anesthetic effects on ischemic myocardium.
AB  - Volatile anesthetics, particularly the new generation of agents, have a very
      rapid onset and offset of action. These properties allow for quick recovery from
      clinical anesthesia. Because there is additional evidence that these agents have
      protective effects during myocardial ischemia, there may be advantages for 'fast
      tracking' patients undergoing coronary revascularization procedures.

PMID- 17013250
TI  - Perioperative analgesia with non-steroidal analgesics.
AB  - Non-steroidal anti-inflammatory drugs are widely used for perioperative analgesia
      as a sole analgesic after minor surgical procedures and in combination with other
      types of analgesics after major surgery. The development and use of new selective
      cyclo-oxygenase-2 inhibitors hopefully reduce the likelihood of perioperative
      adverse effects that may prevent the use of non-steroidal anti-inflammatory
      analgesics in many patients. It remains to be determined, however, whether they
      can offer effective analgesia with minimal risks of side-effects in everyday
      clinical use.

PMID- 17013252
TI  - Alternative-site anesthesia: guidelines affecting clinical care.
AB  - The delivery of anesthesia care to patients in alternative sites outside the
      operating room is a rapidly growing area of clinical activity. We have reviewed
      our patient care guidelines and standards developed for the operating room and
      applied them to sites as varied as a magnetic resonance imaging center in
      radiology to a plastic surgery office. Now specific societies and guidelines are
      being developed for alternative site practice.

PMID- 17013253
TI  - Anaesthesia care and the adult cardiac catheterization patient.
AB  - The number and types of procedures being performed in the adult cardiac
      catheterization suite have increased dramatically, with an aggressive move
      towards percutaneous interventional cardiac procedures. Here we review many of
      these procedures, including the current trends in North America and Europe.
      Coronary angioplasty is now more commonly performed than coronary artery bypass
      grafting. The past 5 years have seen a proliferation of coronary stenting
      procedures. Restenosis of coronary arteries continues to be a major area of
      research and concern.

PMID- 17013254
TI  - Office-based anaesthesia.
AB  - Office-based anaesthesia is a young but rapidly growing speciality practice. In
      patient selection, surgical procedures, and anaesthetic techniques this practice
      is similar to standard ambulatory surgery; however, the liability and risks of
      office-based anaesthesia are greater. The anaesthesiologist's major challenge is
      to insist on patient safety in this developing field.

PMID- 17013255
TI  - Anaesthetists as pain management consultants.
AB  - Anaesthetists who manage acute and chronic pain need to be familiar with current
      research and practice guidelines in these areas. New local anaesthetics and new
      routes of administration for opioids and adjuvants may further improve our
      management of acute pain. The safety of epidural analgesia in combination with
      low molecular weight heparins and the role of the anaesthetist on the acute pain
      service are reviewed. Chronic pain disability is increasing, necessitating a re
      evaluation of our approach to chronic pain. The limitations of nerve blocks are
      acknowledged and guidelines for managing chronic pain and opioids are available.
      Anaesthetists must recognize psychological difficulties as a significant
      perpetuating factor in chronic pain.

PMID- 17013256
TI  - Anaesthesia and palliative care.
AB  - Palliative medicine provides end-of-life care to terminally ill patients with a
      focus on pain and symptom management, psychosocial and spiritual support and
      bereavement follow-up. This article reviews some of the more recent literature on
      the subject of palliative care focusing on educational barriers to quality
      palliative care, advances in quality assessment, and advances in pain and symptom
      management.

PMID- 17013258
TI  - Monitoring of the central nervous system.
AB  - Clinical studies have shown a close relationship between variables such as
      hypoxia, increased intracranial pressure, arterial hypotension, or seizures and
      neurological outcome. This indicates the need for monitoring techniques of the
      central nervous system including measurements of cerebral blood flow, cerebral
      oxygenation and neuronal function. Semiquantitative changes in cerebral blood
      flow can be measured continuously using transcranial Doppler sonography.
      Measurements of jugular venous oxygen saturation or tissue oxygenation reflect
      the balance between cerebral oxygen delivery and cerebral oxygen demand. Near
      infrared spectroscopy appears to be a technology with potential for non-invasive
      measurements of cerebral oxygen saturation and mitochondrial oxygen availability.
      The current technology is, however, of limited clinical utility. Brain electrical
      monitoring techniques such as electroencephalogram and evoked potentials are
      sensitive and specific to detect changes in neuronal function caused by cerebral
      ischaemia. Electroencephalogram and evoked potential measurements of depth of
      anaesthesia and specific electroencephalogram patterns for pharmacodynamic
      quantification of drug effects may gear the dosage of anaesthetics according to
      the anaesthetic effect.

PMID- 17013259
TI  - Anaesthetic considerations for acute spinal cord injury.
AB  - The recently published research data on the possible pathophysiology of acute
      spinal cord injury provide the basis of a number of exciting possibilities for
      its treatment. The present article reviews these lines of investigation. It
      focusses on methylprednisolone, which is the only effective proven therapy to
      limit secondary spinal cord injury known to date. In addition, the initial
      evaluation of patients with possible spinal cord trauma and airway management in
      patients with cervical spine injury are also discussed. Finally, the anaesthetic
      regimen in patients with these injuries is reviewed, showing that no anaesthetic
      agent or technique is superior to other anaesthetic methods.

PMID- 17013260
TI  - Head injury: complications and management.
AB  - Considerable effort and substantial funding has gone towards the development of a
      neuroprotective agent that could be given after brain trauma to reduce mortality
      and improve functional recovery. There have been many failed or inconclusive
      studies to date. In Europe two promising studies have been stopped or shelved
      (Lubeluzole, Janssen-Cilag and BAYx3702, Bayer) and the future of pharmacological
      neuroprotection after traumatic brain injury is in doubt. Clinicians managing
      patients with a head injury are therefore left with the detection and prevention
      of secondary insults to the brain, including the management of medical
      complications of brain injury, and non-pharmaceutical interventions that might
      beneficially modify the brain's response to trauma. Of the potential
      interventions, moderate hypothermia is the most promising.

PMID- 17013261
TI  - Anesthesia for carotid endarterectomy.
AB  - Patients presenting for carotid endarterectomy provide anesthesiologists with
      many challenges. These include optimization of cerebrovascular hemodynamics and
      oxygen balance, as well as minimizing myocardial risk. Fiscal pressures have
      encouraged the development of clinical pathways in many centers, with a
      remarkable trend towards decreased intensive care unit utilization and length of
      hospital stay. Anesthetic and surgical practices vary widely, but outcomes in
      these high-risk patients are usually excellent despite these differences. The
      potential for expanded indications for carotid endarterectomy and development of
      percutaneous treatment for carotid stenosis will provide neurovascular
      anesthesiologists with additional incentives to refine the anesthetic management
      of these patients.

PMID- 17013262
TI  - Neuroprotection (including hypothermia).
AB  - There have been over 2000 publications in the last year addressing the topic of
      neuroprotection. Novel and emerging therapeutic targets that have been explored
      include cerebral inflammation, hypothermia, neural transplantation and repair and
      gene therapy. Unfortunately, with few exceptions, the successes of experimental
      neuroprotection have not been translated into clinical practice. The possible
      reasons for the discrepancy between experimental success and clinical benefit are
      explored.

PMID- 17013264
TI  - Update in regional anesthesia for shoulder surgery.
AB  - Recent advances in the application of regional anesthesia to the care of patients
      undergoing shoulder surgery are discussed. New techniques for the management of
      postoperative pain are highlighted, with an emphasis on interscalene patient
      controlled analgesia and suprascapular block. New developments in the safety and
      effectiveness of brachial plexus block are presented. The technique of
      interscalene block used at our institution is discussed in detail. Intraoperative
      hypotension and bradycardia caused by activation of the Bezold-Jarisch reflex is
      considered. The ongoing debate regarding the use of paresthesia versus nerve
      stimulator techniques is examined.

PMID- 17013265
TI  - Regional blocks for cesarean section.
AB  - Recent researches in the field of regional anesthesia for cesarean section have
      focused on spinal anesthesia, including prophylaxis of maternal hypotension, the
      use of opioids to improve intra- and postoperative analgesia and the use of
      ropivacaine.

PMID- 17013266
TI  - Unilateral spinal anaesthesia: gadget or tool?
AB  - The results of different studies investigating the use of unilateral spinal
      anaesthesia are confusing and partly inconsistent. Some authors doubt whether it
      is possible to create a strictly unilateral block (i.e. motor, sensory and
      sympathetic) at all, while others claim that such a procedure is standard,
      especially for ambulatory anaesthesia. This review considers those factors which
      are relevant, plausible and proven.

PMID- 17013268
TI  - Pain therapy.

PMID- 17013267
TI  - Central neuroaxis blockade and coronary circulation.
AB  - The coronary circulation is subject to modulation by the autonomic nervous
      system. Thus, sympathetic stimulation causes coronary vasodilation in healthy
      humans, whereas stenotic coronary arteries react by vasoconstriction in response
      to sympathetic stimulation. It is for this reason that experimental studies and
      clinical evidence revealed beneficial effects of a blockade of cardiac
      sympathetic drive by thoracic epidural anaesthesia on coronary perfusion and
      myocardial function in normal and in ischaemic myocardium. In contrast, segmental
      lumbar epidural anaesthesia leads to a compensatory increase in cardiac
      sympathetic outflow which may jeopardize myocardial areas dependent on perfusion
      by stenotic coronary arteries.

PMID- 17013269
TI  - Long-term effects of nerve blocks in chronic pain.
AB  - Regional blockade techniques have been of crucial importance for decades in
      chronic pain therapy, but in recent years some developments have made a new
      definition of the status of invasive procedures necessary. The realization of
      chronic pain as a multifactorial process led to the establishment of an
      interdisciplinary approach to pain therapy, leaving blockades as only one step in
      a multimodal therapy. The mainstay of local anaesthetic blocks now is diagnostic
      and prognostic, but correct interpretation of the results is limited by different
      factors, and controlled studies on the diagnostic value of local anaesthetic
      blockade are lacking. In cancer pain, invasive procedures are necessary in only a
      few cases. Some neuroablative techniques can offer long-term pain reduction. In
      non-cancer pain, neurodestructive procedures should be reserved for some special
      indications (e.g. lumbar sympathetic neurolytic blocks in ischaemic diseases). In
      a great number of chronic pain conditions the sympathetic nervous system is
      involved or even has a central status. In the acute stage of these diseases
      sympathetic blockades can be the therapy of choice. There is no disease in which
      different invasive procedures are performed so frequently and so uncritically as
      in chronic low back pain. Up to now, however, all controlled studies of invasive
      procedures only demonstrated short-term effects and failed to prove long-term
      efficacy. Therefore any invasive technique should only be performed in well
      selected patients over a defined period and with a limited number of blockades.

PMID- 17013270
TI  - Measurement in pain therapy: is pain relief really the endpoint?
AB  - Pain is not an isolated symptom. Severe pain creates fatigue, impairs
      concentration, compromises mood, degrades sleep and diminishes overall activity
      level. The goal of intervention for chronic pain must include alleviating the
      functional impairment that pain produces as well as its discomfort. Evaluating
      treatment outcome requires: (1) quantification of both pain intensity and pain
      related impairment; and (2) review of how the relationship between these
      variables changes as a function of treatment. Simply tracking pain intensity
      level as an indicator of pain relief is insufficient and can lead to
      misinterpretation of the effects of an intervention.

PMID- 17013271
TI  - Side-effects of opioids in chronic pain treatment.
AB  - The emergence of opioid-induced neurotoxicity has gained increasing recognition
      in the literature in the past decade. Exciting developments at the receptor and
      intracellular level have revealed some insights into the potential mechanisms
      underlying this phenomenon. The hitherto reported clinical benefits of opioid
      rotation and dose reduction in the treatment of opioid toxicity warrant further
      clarification in prospective studies, particularly in relation to their relative
      value.

PMID- 17013272
TI  - Psychological approaches in pain management: what works?
AB  - Outcome studies evaluating psychological treatments for pain vary in nature and
      intensity. Overall, however, treatment programs that include psychological
      interventions have been shown to be effective in treating postoperative pain,
      noncardiac chest pain, fibromyalgia syndrome, and chronic back pain. Cost
      analyses of the treatments indicate not only the clinical efficacy but the cost
      effectiveness of psychological interventions. Issues related to subject
      attrition, noncompliance, and individual differences in treatment response should
      be addressed in future studies.

PMID- 17013273
TI  - Predictors of efficacy in treatment of chronic low back pain.
AB  - The investigation of predictors for therapy outcome in patients with chronic low
      back pain date back to the early 1970s. Numerous well controlled prospective
      longitudinal studies have confirmed the predominant predictive power of several
      psychological factors, which are in addition to objective work related, medical
      and sociodemographic variables. Studies published in the review period have
      reported markedly improved methodological standards. Further progress is seen
      with the enhanced search for predictors of working situation in chronic low back
      pain patients. Finally, there is a shift toward the investigation of predictors
      for efficacy of primary care in acute and subchronic low back pain patients.

PMID- 17013274
TI  - Weak opioids--an educational substitute for morphine?
AB  - The World Health Organization guidelines suggest the use of weak opioids on the
      second step of the analgesic ladder for cancer pain relief. Weak opioids are
      important substitutes for low doses of morphine, although their analgesic
      efficacy is lower than that of non-opioid or strong opioid analgesics. The use of
      weak opioids has great educational impact and has helped spread the use of the
      guidelines. Furthermore, weak opioids are more freely available and are expected
      to have a better side-effect profile. Controlled long-term studies are required
      for confirmation.

PMID- 17013275
TI  - Axillary and midhumeral approach for plexus block.
AB  - Many variations of the axillary approach for blocking of the brachial plexus have
      been described. The axillary approach tends to be the technique with the lowest
      risk of serious complications; in particular, there is no risk of pneumothorax. A
      fairly high failure rate and an onset time of 20-40 minutes is why this
      technique, first described by Hirschel in 1911, is still discussed. Ideally,
      axillary brachial plexus blockade would be achieved using a technique that was
      easy and quick to perform with a fast onset time, a 100% success rate and without
      any risk for the patient; but, as all studies show, this goal is still far away.

PMID- 17013277
TI  - Volatile versus intravenous anaesthetic techniques for ambulatory anaesthesia.
AB  - This review considers the role played by volatile and intravenous agents in the
      induction and maintenance of anaesthesia for ambulatory surgery. The speed and
      ease of induction, maintenance and recovery, and associated advantages such as
      the facilitation of airway manoeuvres, side-effect profiles and economic
      influences are considered.

PMID- 17013278
TI  - What is new in monitored anesthesia care?
AB  - The use of monitored anesthesia care (MAC) techniques is increasing in popularity
      because recovery profiles seem to be improved compared with general and regional
      anesthesia. This article describes the conceptual basis for MAC and reviews the
      current MAC practices.

PMID- 17013279
TI  - Fast-track concept for ambulatory anesthesia.
AB  - Fast-tracking in the ambulatory setting refers to the ability to transfer
      suitably recovered patients from the operating room directly to the Phase II
      (step-down) recovery area, bypassing the postanesthesia care unit. This article
      describes the concept of fast-tracking after ambulatory surgery and reviews
      anesthetic techniques that have helped to facilitate this process. The prevention
      and management of postoperative pain and nausea are also discussed.

PMID- 17013280
TI  - Office-based surgery and anesthesia.
AB  - Health care delivery is undergoing a revolutionary change. It is focusing rapidly
      all over the world towards outpatient and home care. One of the most obvious
      results of these changes has been the relative explosion office-based surgery and
      anesthesia; however, these are not new concepts. Dentistry and office-based
      anesthesia have always been closely intertwined. In 1844, two dentists, Wells and
      Morton, changed the practice of anesthesia firstly with the use of nitrous oxide
      and secondly with ether for tooth extraction. Thereafter, office-based surgery
      and anesthesia continued to evolve. In the past two decades, the rapid
      development of new surgical technologies and pharmaceuticals have facilitated the
      movement of more invasive surgical procedures and anesthesia to less invasive
      settings, such as the doctor's office. The most significant recent changes in
      health care are changes in the consumer, the practitioner and the provider. All
      are demanding high quality anesthesia and surgery care at a reduced cost.
      Articles describing almost every type of surgical and anesthetic techniques in
      the office can be found in the literature. However, the success of providing safe
      and cost-effective surgical and anesthetic care at an office depends on major
      issues, including adequate selection of the surgical procedure, complete
      preoperative assessment of the patient's state of health and adequate equipment
      and design of the unit. It is incumbent upon practitioners to make certain that
      the safety of the hospitals is not sacrificed in the office setting. Health care
      has to be delivered as safely in the office as it would be elsewhere. Regulations
      and guidelines should be established in consultation with surgeons,
      anesthesiologists and administrators to ensure safe health care. These guidelines
      should be based on the specific type of surgery, the level of anesthetic required
      and the design of the office. This way the provision of adequate quality of care
      is ensured. Office-based anesthesia and surgery will no doubt continue to evolve
      because it is safe, pleasing and convenient for the patient and of low cost.

PMID- 17013281
TI  - Recovery care facilities.
AB  - In a world of rapidly changing policies in healthcare and the constant search for
      value-based medical care, the anaesthesiologist must be aware of new anaesthetic
      drugs and techniques utilized in daily practice, and most importantly, be updated
      on the implications of using these techniques in the ambulatory (day-case)
      setting without compromising patient safety or jeopardizing the physician-patient
      relationship. The ambulatory surgery movement has led to some of the most
      substantial changes in anaesthesia, with special emphasis on recovery care when
      the patient is rapidly brought into contact with their relatives or escorts
      shortly after emerging from a sedative or anaesthetic state.

PMID- 17013282
TI  - Extending the limits: minimally invasive surgery.
AB  - Minimally invasive technology is being applied to an increasing number of
      surgical procedures. It remains to be seen which techniques will eventually
      become a 'gold standard' as has the laparoscopic cholecystectomy, and which will
      fall by the wayside. In the meantime, anesthesiologists must be aware of the
      unique requirements and complications of laparoscopic surgery.

PMID- 17013283
TI  - About evidence and time.

PMID- 17013284
TI  - Advances in pulse oximetry.
AB  - The interaction between light and tissue is the basis of pulse oximetry. This
      review focuses on the recent development of pulse oximetry, with special emphasis
      on the reflection oximetry utilized in fetal and cerebral oximetry.

PMID- 17013285
TI  - Benefits, risks and alternatives of pulmonary artery catheterization.
AB  - Twenty-five years after the introduction of the pulmonary artery catheter in
      clinical practice, its effectiveness in improving patient outcome is seriously
      questioned. Experts still recommend to use pulmonary artery catheters in selected
      critically ill patients, although evidence supporting these recommendations is
      lacking. The risks and the unclear benefits associated with this procedure should
      prompt the search for alternative, noninvasive monitoring techniques.

PMID- 17013286
TI  - Factors influencing vigilance and performance of anesthetists.
AB  - As a group, anesthetists have been the leaders in medicine in the study of
      vigilance, performance, and safety. This review updates the work that has been
      done in the last year regarding the study of anesthetist vigilance and
      performance. Much of this work has been performed with the use of patient
      simulators.

PMID- 17013287
TI  - Feedback control of anaesthesia.
AB  - Feedback control of anaesthesia can improve the quality of patient care while
      reducing the administration and cost of anaesthetic drugs. Systems have been
      available for several years to control blood pressure and neuromuscular blockade.
      Control of anaesthetic depth has been reported using the median frequency of the
      electroencephalogram. Recently, the monitoring of anaesthetic depth using the
      bispectral index or auditory evoked potentials has greatly improved feedback
      control of the depth of anaesthesia.

PMID- 17013288
TI  - Information systems and multimedia as educational tools.
AB  - Electronic publication uses video, sounds, and pictures to present some ideas
      (e.g. characteristics of a heart murmur) that may be difficult to convey with
      printed text, and is changing the way in which physicians communicate.

PMID- 17013289
TI  - Innovative approaches to the management of patients with cardiovascular disease:
      looking forward to the 21st century.

PMID- 17013290
TI  - Anesthetic implications of new surgical approaches to myocardial
      revascularization.
AB  - New surgical techniques for bypassing coronary artery lesions are being explored
      with the goals of avoiding cardiopulmonary bypass, minimizing disfiguring scars,
      and decreasing hospital stay and costs. These forms of cardiac surgery have
      significant anesthetic implications. Intraoperatively there is an obligatory
      period of myocardial ischemia, which may lead to significant hemodynamic
      consequences. Postoperative trends towards early extubation and patient
      mobilization require anesthetic techniques that facilitate rapid recovery.

PMID- 17013291
TI  - Non-invasive cardiac output determination: state of the art.
AB  - This review deals with recent developments in non-invasive cardiac output
      measurement. In the past few years significant progress has been made with semi
      invasive transoesophageal echocardiography; the method now provides advanced
      facilities to measure cardiac output and other important characteristics of
      cardiac function. The method is, however, operator-dependent and the equipment
      used is expensive, which means that large-scale use on intensive care patients is
      not feasible. Whole-body impedance cardiography has recently shown good accuracy
      and flexibility in use, and seems to be the most promising method for the non
      invasive measurement of cardiac output.

PMID- 17013292
TI  - Angioplasty and noncardiac surgery: risks of myocardial infarction.
AB  - Prophylactic percutaneous transluminal coronary angioplasty is one
      revascularization strategy employed to reduce risks of cardiac complications
      after noncardiac surgery in certain patients. Reduced adverse cardiac event rates
      are at least partially offset by costs and complications of angioplasty. Patients
      who undergo noncardiac surgery within 90 days of coronary angioplasty may be at
      increased risk for postoperative cardiac complications.

PMID- 17013293
TI  - Cardiopulmonary bypass: new strategies for weaning from cardiopulmonary bypass.
AB  - This review focuses on weaning from cardiopulmonary bypass, a very critical time
      for patients and anaesthetists and frequently requiring major therapeutic effort.
      Few novel strategies for weaning have been described recently. Most drugs or
      approaches described during the review period are already well established.
      Emphasis is placed on the importance of non-cardiac factors, and on the
      importance of diastolic ventricular function as opposed to systolic function.

PMID- 17013294
TI  - Lung separation in the patient with a difficult airway.
AB  - During video-assisted thoracoscopy the lungs should be well collapsed to allow
      the surgeon an optimal view of the surgical field. The use of 'difficult tubes'
      such as the double lumen tube or Univent cannot be avoided despite the presence
      of a difficult airway. If it is only possible to place a single lumen tube, a
      tube exchanger can be used to switch to a double lumen tube or a Univent tube.
      Alternatively, a Fogarty embolectomy catheter can be passed down the single lumen
      tube as an independant bronchial blocker. The Bullard and the Wu laryngoscopes
      and the laryngeal airway mask can further assist in establishing an airway.
      Finally, depending on the extent and the length of the procedure, an airway,
      initially not classified as difficult, may become difficult and postoperative
      planning is a must.

PMID- 17013295
TI  - Nitric oxide and almitrine: the definitive answer for hypoxemia.
AB  - Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion
      ratio distribution towards shunt or low ventilation/perfusion zones.
      Pharmacological modification of pulmonary blood flow distribution improving
      ventilation/perfusion ratio should correct hypoxia. The development of inhaled
      nitric oxide therapy had confirmed this concept, but with a relatively high
      proportion of 'non responders'. Then development of other drugs used alone or in
      association with nitric oxide may reinforce the benefit of nitric oxide. This has
      been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic
      pulmonary vasoconstriction. Using inhaled nitric oxide in combination with
      almitrine, several studies in adult respiratory distress syndrome or acute lung
      injury patients have shown spectacular results in term of PaO2 and pulmonary
      shunt reduction. Moreover, the proportion of responders to this combination seems
      largely great than those observed for each drug alone. In conclusion, pulmonary
      blood flow manipulation improving ventilation/perfusion mismatching is one of the
      major strategies to correct severe hypoxia.

PMID- 17013296
TI  - Hypoxic pulmonary vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction is a local reflex in the lung that diverts
      blood away from poorly oxygenated regions. Improvements in understanding of
      modulators of this response have led to pharmacologic methods whereby V/Q
      matching may potentially be improved in certain types of pulmonary pathology and
      during anesthesia for thoracic surgical procedures.

PMID- 17013297
TI  - Post-pneumonectomy pulmonary edema: is anesthesia to blame?
AB  - Post-pneumonectomy pulmonary edema is a major cause of early mortality following
      lung resection surgery. It is not clear whether this complication is caused by
      excessive perioperative intravenous fluid as was previously thought. The recent
      demonstration of increased pulmonary capillary permeability of the lung following
      a pneumonectomy suggests measures to try and decrease the incidence of this
      highly lethal syndrome. These measures include the judicious use of intravenous
      crystalloids, avoidance of lung hyperinflation and efforts to minimize the
      pulmonary artery pressure.

PMID- 17013299
TI  - Current world literature.

PMID- 17013298
TI  - Post-thoracotomy pain control.
AB  - Publications on post-thoracotomy pain control obtained by Medline search were
      reviewed from June 1997 to July 1998. The main focus points in the past year were
      the effect of new surgical techniques on analgesia after thoracic surgery and the
      use of extrapleural catheters in the paravertebral space as a method of
      continuous intercostal nerve block. Epidural and patient-controlled analgesia
      techniques are still widely used and are mostly effective, but some patients may
      still have unacceptable levels of pain in the first 24 hours.

PMID- 17013300
TI  - Intensive care.

PMID- 17013301
TI  - Strategies to prevent organ failure.
AB  - The gastrointestinal tract and the generalized inflammatory response initiated by
      severe injury or infection have been implicated in the pathophysiology of
      multiple-organ system failure. Once multiple-organ system failure has occurred,
      treatment focuses on supporting end-organ function. Recent studies have shown,
      however, that it may be possible to reduce the incidence and prevalence of
      multiple-organ system failure by controlling the reperfusion injury cascade,
      normalizing gastrointestinal blood flow and preserving the integrity of the
      gastrointestinal immune barrier.

PMID- 17013302
TI  - New evaluation therapies for sepsis.
AB  - This article presents an analysis of the literature of the last 2 years on the
      treatment of sepsis and septic shock. It appears that most of the antimediator
      therapies applied in phase II or III clinical trials yielded disappointing
      results. But, many other therapeutic approaches are proposed or are ongoing, and
      many papers report critical analysis of the reasons for the lack of success of
      past clinical trials.

PMID- 17013303
TI  - Monitoring cardiac function without the use of a pulmonary artery catheter.
AB  - Investigators have been trying to develop ways to measure cardiac function that
      are less invasive and more cost-effective than a pulmonary artery catheter. None
      of the technologies currently available are yet ready for routine use in
      assessing cardiac function in the operating room and in the intensive cardiac
      unit.

PMID- 17013304
TI  - Newer ventilatory strategies.
AB  - Over the past year a large number of innovations in mechanical ventilation have
      been evaluated. Three of the most exciting are non-invasive positive pressure
      ventilation, tracheal gas insufflation and partial liquid ventilation. Non
      invasive positive pressure ventilation is now clearly a standard of care in the
      management of an acute exacerbation of chronic obstructive pulmonary disease. In
      addition, its use in other clinical settings is being actively explored. Tracheal
      gas insufflation appears to be a useful adjunct to mechanical ventilation for the
      management of carbon dioxide but requires manufacturer-designed devices for safe
      application. The effects of partial liquid ventilation on lung injury have been
      more clearly defined in the past year as well as approaches to provide gas
      ventilation during partial liquid ventilation.

PMID- 17013305
TI  - Inhaled vasodilator therapy for treatment of acute lung injury.
AB  - In randomized controlled trials, inhaled nitric oxide failed to provide
      significant clinical benefit in patients with acute lung injury. Despite
      temporary improvement in oxygenation, inhaled nitric oxide neither improved
      survival, nor decreased length of mechanical ventilation. Thus, with the
      exception of severe hypoxaemia refractory to conventional therapy, inhaled nitric
      oxide is not indicated in patients with acute lung injury. Inhalation of
      prostacyclin and prostaglandin E1, respectively, has been associated with an
      improvement in oxygenation and a decrease in pulmonary artery pressure.
      Prospective randomized trials are warranted to assess the impact of inhaled
      prostaglandins on the outcome of patients with acute lung injury.

PMID- 17013307
TI  - Resuscitation and trauma anaesthesia.

PMID- 17013306
TI  - Transfusion therapy in the critically ill.
AB  - Blood transfusion remains an important part of treatment in critically ill
      patients. While the known infectious risks continue to decrease, concerns remain
      about the effects of allogeneic blood on the immune system. Some patients
      tolerate anemia much better than others; the optimal hemoglobin level, however,
      is difficult to define in any individual patient.

PMID- 17013308
TI  - Assisted ventilation for bystander-initiated cardiopulmonary resuscitation.
AB  - Mouth-to-mouth rescue breathing is a barrier to the performance of bystander
      cardiopulmonary resuscitation. Experimental data suggest that mouth-to-mouth
      rescue breathing may not be necessary for brief periods of bystander
      cardiopulmonary resuscitation until defibrillation is available. These data are
      insufficient to recommend changes in cardiopulmonary resuscitation guidelines,
      but are compelling enough to recommend further experimental and human trials.

PMID- 17013309
TI  - Ventilation and cardiopulmonary resuscitation.
AB  - Ventilation is essential for oxygenation of the alveoli and arterial blood.
      Comatose humans have upper airway soft tissue obstruction unless the head is
      tilted backwards and sometimes, in addition, the jaw thrust forward. In 1960,
      measurements on comatose humans with or without cardiac arrest, with or without a
      tracheal tube, showed essentially no ventilation by sternal compressions alone.
      This led to combining step A (airway control), step B (mouth-to-mouth
      ventilation), and step C (sternal (cardiac) compressions) into basic life
      support. In animal models, sternal compressions alone can produce some
      ventilation with or without a tracheal tube, because the straight upper airways
      of animals do not obstruct in coma. In witnessed sudden cardiac death, the C-A-B
      sequence makes physiological sense, but other causes of sudden coma need the A-B
      C sequence. Lay persons should continue to be taught cardiopulmonary
      resuscitation steps A-B-C.

PMID- 17013310
TI  - End-tidal carbon dioxide and resuscitation.
AB  - In this review, we attempted to summarize the effectiveness and the limitation of
      end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. End
      tidal carbon dioxide can be an indicator of the real return of spontaneous
      circulation and can also be an indicator of the effectiveness of cardiac massage.
      We cannot, however, estimate the prognosis of cardiopulmonary resuscitation from
      the end-tidal carbon dioxide value. We concluded that cardiopulmonary
      resuscitation should never be abandoned for the sole reason that the end-tidal
      carbon dioxide value is low.

PMID- 17013311
TI  - Pre-hospital thrombolysis.
AB  - The administration of thrombolytic drugs outside hospital by emergency physicians
      is becoming more common. However, few in Europe live in areas where such a
      service is provided. The data suggest that the advantages can be appreciable in
      some circumstances but that the strategy may not be universally applicable.

PMID- 17013312
TI  - Electrical defibrillation: new technologies.
AB  - Two-thirds of deaths from coronary disease occur in the pre-hospital phase and
      are caused by ventricular fibrillation or pulseless ventricular tachycardia, for
      which electrical defibrillation is the only effective treatment. The time delay
      between the onset of ventricular fibrillation and the administration of the first
      defibrillatory shock is the most important determinant for survival. To achieve
      the earliest defibrillation possible, rescuers others than physicians need to be
      able to initiate this treatment. The international scientific community strongly
      supports the concept of early defibrillation in the setting of a strong chain of
      survival. New technological developments of automated external defibrillators
      (AEDs) allowed the implementation of defibrillation by the first responding
      professional rescuer. As a consequence of the technological evolution in
      implantable defibrillators, much research has also been done on new
      defibrillation waveforms and alternative energy levels in external
      defibrillators. After initial animal research, human clinical investigation has
      shown that initial low energy (150J) nonprogressive (150J-150J-150J) impedance
      adjusted biphasic waveform defibrillatory shocks for patients in out-of-hospital
      ventricular fibrillation are safe, acceptable and clinically effective. Reporting
      on outcome from cardiac arrest must be as uniform as possible to allow
      conclusions on performance of emergency medical service systems. The 'Utstein
      Style' nomenclature is a glossary of terms and a reporting guideline for uniform
      description of cardiac arrest, resuscitation, the emergency medical service (EMS)
      system and the outcome. Reports on experiences with AED programmes by traditional
      and non-traditional professional rescuers support the view that AEDs should not
      be implemented in EMS systems as an isolated intervention, but that efforts are
      equally needed to strengthen the other links of the chain of survival. The
      international scientific community (American Heart Association, International
      Liaison Committee on Resuscitation and European Resuscitation Council) have
      issued guidelines for the use of AEDs by EMS providers and first responders, and
      a universal treatment algorithm is proposed.

PMID- 17013313
TI  - Modified haemoglobins and perfluorocarbons.
AB  - After decades of research activities and product improvements in the field of
      artificial oxygen carriers based on either haemoglobin modifications or
      perfluorocarbon emulsions, these products have reached a critical stage of their
      development. Varieties of haemoglobin-based oxygen carriers and perfluorocarbon
      emulsions are under current clinical investigation. Although the clinical
      availability of artificial oxygen carriers may result in profound changes of
      fluid resuscitation from haemorrhage, the transfusion of human blood components
      as an integral part of medical trauma management will not be replaced. However, a
      rapid and effective restoration of tissue oxygenation by the use of artificial
      oxygen carriers in the treatment of severe haemorrhage may bridge time delays
      until stored and cross-matched human packed red cells are available. Whether
      artificial oxygen carriers could provide additional clinical benefits by
      sustaining tissue oxygenation even under conditions of a disturbed macro- or
      microcirculation is the subject of current investigations. Therefore, the
      application of safe and effective artificial oxygen carriers would not only be
      restricted to the treatment of severe haemorrhage, but additional therapeutic
      indications of artificial oxygen carriers in emergency medicine, trauma
      anaesthesia and other medical specialities would emerge.

PMID- 17013314
TI  - Ethical dilemmas in intensive care: can the problem be solved?
AB  - There is a lack of consistency in ethical decision-making with regard to forgoing
      life-support, which demands increased efforts to improve clinical competence in
      end-of-life care, e.g. by proactive ethics consultation or early exploration and
      documentation of the patient's wishes and preferences. Another current ethical
      issue is the allocation of limited resources; recent guidelines provide a useful
      framework for bedside practitioners and health policy makers.

PMID- 17013315
TI  - Cost-effectiveness analysis in anaesthesia.
AB  - In order to preserve the quality of anaesthetic care under cost containment
      programmes, the concept of value-based anaesthesia was introduced. To achieve
      this goal, namely, the provision of the best possible care attainable at a
      reasonable cost, studies are necessary that compare anaesthetic techniques in
      terms of both quality and costs, e.g. by means of cost-effectiveness analyses.

PMID- 17013316
TI  - Clinical outcomes research: the international perspective.
AB  - The decade of the 1990s has seen worldwide emphasis on the containment of
      healthcare costs. Much of the limitation of cost has been carried out at the
      perceived potential decrement in the quality and outcome of the delivery of
      patient care. This concern has not been limited to countries with traditional
      indemnified insurance (USA) or the more social based healthcare programs of the
      European countries and Canada. As physicians, we have not effectively utilized
      research methodology in establishing which therapeutic interventions are both
      cost effective and beneficial. A concerted worldwide effort by clinicians of all
      disciplines will be necessary to effect cost reduction and improved outcomes.

PMID- 17013317
TI  - Evidence-based methods to improve anaesthesia and intensive care.
AB  - This review concerns the application of the methods of clinical epidemiology to
      problems in anaesthesia and intensive care. It explores the quality of evidence
      to guide clinical decision-making and health policy provided by experimental and
      various non-experimental research designs. Ten recent publications in anaesthesia
      and intensive care are analysed to provide relevant examples.

PMID- 17013318
TI  - Impact of audit systems on the quality of care.
AB  - Audit and other means of scrutiny are an essential part of professional clinical
      practice. However, if we and our patients are to benefit fully from audit, its
      processes must be supported by the necessary organizational changes to allow
      improvements to be made to our systems of care.

PMID- 17013320
TI  - Current world literature. Intensive care.

PMID- 17013319
TI  - Involvement of an anaesthetic department in terminal therapy.
AB  - The goal of hospital treatment in terminal therapy must be a functional
      integration of all modes of care including psychosocial support.
      Anaesthesiologists who practise pain management and critical care medicine are
      predestined to care for terminally ill patients and their families. An
      anaesthetic department can assume superordinate responsibilities within the
      organization of a palliative network coordinating inpatient and outpatient
      arrangements.

PMID- 17013321
TI  - Informed consent: is it possible during labor?

PMID- 17013322
TI  - Postdural puncture: implications and complications.
AB  - Postdural puncture headache is a distressing potential complication of spinal and
      epidural anesthesia. This article reviews the currently held thoughts on the
      topic, with a focus on the cause, prevention and treatment of postdural puncture
      headache.

PMID- 17013323
TI  - Morbidity and mortality from obstetric anaesthesia in the 1990s.
AB  - As anaesthetic-related maternal mortality reduces in the developed world,
      alternative indicators of obstetric anaesthetic quality are required. Serious
      morbidity is difficult to define and quantify, but can be reduced by the
      provision of effective critical care. Regional anaesthesia, although safer than
      general anaesthesia, is not without risks. Evidence-based strategies exist to
      reduce the risks.

PMID- 17013324
TI  - The changing role of magnesium sulphate therapy.
AB  - Magnesium sulphate is not an effective tocolytic. Magnesium sulphate therapy was
      also linked to preterm neonatal deaths in one study, which was stopped before
      completion. Other studies suggest a possible neuroprotective effect of magnesium.
      Both of these issues require further study. Magnesium sulphate is clearly the
      drug of choice to prevent recurrent eclampsia and to treat severe pre-eclampsia.

PMID- 17013325
TI  - New developments in fetal monitoring for the anesthesiologist.
AB  - Assessing fetal wellbeing has evolved from the ancient awareness of 'quickening'
      to a vast array of biophysical, imaging and biochemical methods. Because the
      results of these tests influence the urgency of fetal delivery and sometimes the
      choice of maternal anesthetic technique, it is important for anesthesiologists to
      understand the fundamentals of fetal monitoring and the changing face of new
      developments in this field. Noteworthy publications from the past year on this
      topic include new guidelines for the interpretation of fetal heart monitoring,
      advances in intrapartum fetal pulse oximetry, thresholds of acidosis associated
      with fetal injury, and efforts to decrease cerebral palsy through better
      antenatal biophysical testing.

PMID- 17013326
TI  - Combined spinal-epidural for labor analgesia.
AB  - Since the introduction of the combined spinal-epidural technique in the early
      1980s it has gained increasing popularity for analgesia and anesthesia in labor
      and delivery. The benefit of the rapid onset of analgesia from the intrathecal
      injection, coupled with the flexibility of an epidural catheter that can provide
      a long duration of labor analgesia or conversion to an anesthetic when operative
      delivery is necessary, has made combined spinal-epidural the labor analgesic of
      choice in many obstetric anesthesia practices.

PMID- 17013327
TI  - The expansion of paediatric anaesthesia.

PMID- 17013328
TI  - Thermal regulation and mild intraoperative hypothermia.
AB  - Homeothermic species such as birds and mammals require an almost constant
      internal body temperature to preserve normal physiological and metabolic
      function. When the internal temperature deviates significantly from normal,
      metabolic function deteriorates and death may result. The efficiency of the
      thermoregulatory system is highly affected by the administration of medication
      and by illnesses. Hypothermia may result, especially when these conditions are
      associated with exposure to a cold environment. Because such conditions exist
      during anaesthesia and surgery, the understanding of the physiology of the
      thermoregulatory system and the associated perianaesthetic thermal disturbances
      is essential to a proper intraoperative management. The purpose of this review is
      to provide clinicians with a better understanding of these principles, and also
      to elaborate on the most recent advances in this field, which should help to
      improve intraoperative anaesthetic temperature management.

PMID- 17013329
TI  - Anaesthesia for laparoscopic procedures in infants and children: indications,
      intra- and post-operative management, prevention and treatment of complications.
AB  - This paper reviews the main physiological consequences of the creation of a
      pneumoperitoneum in neonates, infants and young children. Validated indications
      of laparoscopic surgery are reported and the main adverse effects of this type of
      management are detailed as well as the preventive or therapeutic measures
      recommended to limit their negative consequences. Anaesthetic precautions and
      recommendations are developed, both for intra- and post-operative management of
      paediatric patients.

PMID- 17013330
TI  - New developments in the management of the paediatric airway: cuffed or uncuffed
      tracheal tubes, laryngeal mask airway, cuffed oropharyngeal airway, tracheostomy
      and one-lung ventilation devices.
AB  - The use of a cuffed endotracheal tube should no longer be limited by the age of
      the child but by his or her clinical condition (e.g. poor lung compliance). To
      prevent pharyngeal damage, overinflation of the cuff of the laryngeal mask airway
      should be avoided by inflating it with the minimum volume required to maintain an
      effective seal and by monitoring intracuff pressure if nitrous oxide is used.
      Percutaneous tracheostomy in children is still in the experimental stage. New and
      older devices to perform one-lung ventilation in children are also described.

PMID- 17013331
TI  - Combined regional and light general anesthesia: are the risks increased or
      minimized?
AB  - Regional anesthesia during general anesthesia has become increasingly popular in
      recent years. Most pediatric anesthesiologists are proponents of this practice,
      and believe that surgical morbidity is reduced, but controversy remains regarding
      safety. Neuraxial anesthesia during general anesthesia is especially
      controversial. Unfortunately, outcome studies are lacking but the literature
      reflects an absence of reported serious morbidity or mortality.

PMID- 17013332
TI  - 'Off-label' use of drugs in pediatric anesthesia: legal, clinical and policy
      considerations.
AB  - Most drugs used in the care of children have never had appropriate studies
      conducted by the manufacturer which fulfill Food and Drug Administration
      requirements necessary to be included in the 'indications' portion of the package
      insert. Any use not described in the indications of the package insert is
      considered 'off-label'. A number of editorials and hard work by many individuals
      have all resulted in new legislation that hopefully will start to make the
      necessary changes in drug development. This paper will review the pertinent
      issues.

PMID- 17013333
TI  - Influence of co-existing diseases on perioperative morbidity and mortality in
      anaesthetized patients: does the anaesthetic technique prevent complications?

PMID- 17013334
TI  - Management of anaesthesia in elderly patients.
AB  - Increasing numbers of very elderly patients require surgery. Elderly patients are
      at increased risk of perioperative morbidity and mortality because of the high
      incidence of co-existing age-related diseases. With greater experience, outcomes
      from major operations in octogenarians have improved. The increased risks of
      surgery in the elderly must, however, be individually weighed against the
      benefits to be gained from symptom relief and improved quality of life.

PMID- 17013335
TI  - Perioperative renal protection.
AB  - Acute renal failure continues to complicate the postoperative courses of our
      vascular and cardiac surgical patients, dramatically increasing mortality and
      decreasing quality of life when it occcurs. In spite of better understanding of
      the disease, few gains have been made in its prevention. We review its
      pathophysiology and discuss the most recent developments that may eventually lead
      to perioperative renal protection.

PMID- 17013336
TI  - Diabetes mellitus and anaesthesia.
AB  - Diabetes mellitus is the most common endocrinological problem encountered by an
      anaesthetist and its prevalence will increase greatly in the next decade. This
      review focuses on the relevance of a new classification and diagnostic criteria
      for diabetes and the results of the important UK prospective diabetes study group
      trial. Other key areas of interest are the acute treatment of non-insulin
      dependent diabetes (type 2), the management of coronary heart disease and
      vascular reactivity in patients with diabetes.

PMID- 17013337
TI  - Consequences of haemostasis disorders on anaesthestic management.
AB  - New molecular markers of coagulation and fibrinolysis activation have been
      developed and used to identify patient subgroups that frequently develop
      increased procoagulant turnover and, hence, disseminated intravascular
      coagulation and organ dysfunction. The idea of inhibiting the coagulation
      hyperactivation by the administration of antithrombin has led to experimental
      findings that pinpoint an anti-inflammatory action of antithrombin. Preliminary
      clinical trials of high-dose antithrombin administration in sepsis are promising.
      Point-of-care coagulation testing remains controversial since a variety of
      perioperative therapeutic regimens such as aprotinin administration obviously do
      not require 'on-line' coagulation monitoring.

PMID- 17013338
TI  - Malignant hyperthermia: advances in diagnostics and management.
AB  - Real-time monitoring of end-tidal carbon dioxide during anaesthesia aids in the
      early detection of malignant hyperthermia and the occurrence of a rapid increase
      in end-tidal carbon dioxide, associated with unexplained persistent tachycardia,
      well before the core temperature begins to rise. Should malignant hyperthermia
      occur, however, dantrolene permits the dependable reversal of skeletal muscle
      hypermetabolism.

PMID- 17013339
TI  - HIV infection: problems with patients' anaesthetic management and healthcare
      workers' exposure.
AB  - Although infection with HIV has become a global epidemic, current research has
      provided a better understanding of the virus and its effect on the immune system.
      Combinations of new antiretroviral agents have been shown to be effective in
      prolonging the life of infected individuals, and chemoprophylactic regimens have
      been useful in preventing opportunistic infections. Risk factors associated with
      the occupational transmission of HIV have been identified and prevention
      strategies proposed.

PMID- 17013340
TI  - Current world literature. Obstetric and gynaecological anaesthesia.

PMID- 17013341
TI  - Alternate-site anaesthesia: balancing patient care, finances, and entrepreneurial
      spirit.

PMID- 17013342
TI  - Monitoring patients during anaesthesia for radiological procedures.
AB  - The past year has seen a number of reports discussing the future possibilities of
      image-guided surgery and interventional radiology. One of the most exciting
      developments is intra-operative magnetic resonance imaging. The anaesthesiologist
      plays a central role in these developments, ensuring that patients undergoing
      procedures in the radiology department are adequately monitored and safely
      maintained.

PMID- 17013343
TI  - Anesthesia outside the operating room for emergency procedures.
AB  - Non-anesthetists usually provide sedation and anesthesia outside the operating
      room for emergency procedures. Techniques vary from no sedation to deep sedation
      using drugs with a good safety profile and few side effects. Newer methods of
      airway control may allow volatile agents such as sevoflurane to be used.
      Anesthetists may need to join sedation teams if they are to maintain control of
      their specialty.

PMID- 17013344
TI  - Anesthesia and sedation in the endoscopy suite? (influences and options).
AB  - Advances in technology and pharmacology have enabled gastrointestinal
      endoscopists to expand the diagnostic and therapeutic capabilities of the
      specialty. Research into the impact of the endoscopy environment on patient
      stress, acknowledgement of the various patient coping styles, development and
      deployment of procedural preparative programs and information streamlining have
      been shown to be of value in decreasing anxiety and reducing sedative
      requirements. Being aware of procedure-related stressors, and factors associated
      with complications, allows us to tailor our sedation or anesthesia plan to the
      individual patient.

PMID- 17013345
TI  - Morbidity and mortality for alternate-site anesthesia care.
AB  - The bibliography contains very few references from anesthesia literature and a
      preponderance of citations from emergency medicine, radiology and pediatrics
      journals. The reviewed publications include studies addressing the relation of
      drug type and dosages to morbidity and mortality in alternate site locations.
      These studies approach the issue of safety through retrospective analysis of
      techniques that are associated with acceptably low morbidity. The occurrence of
      adverse anesthetic events within formalized sedation programs is also reviewed.
      The low morbidity suggests that the trend of out of the operating room anesthetic
      and sedative use will continue. The ability of formalized sedation programs to
      establish and enforce standards of practice as well as to continually collect
      quality assurance data is a strong endorsement for their continuation.

PMID- 17013346
TI  - The anesthesiologist as physician executive.

PMID- 17013347
TI  - Arginine vasopressin: old drug, new uses.

PMID- 17013348
TI  - Haematological effects of anaesthetics and anaesthesia.
AB  - Halothane is still unique in its ability to inhibit platelet aggregation and to
      increase bleeding time in vivo at clinical concentrations, although sevoflurane
      inhibits platelet aggregation induced by weak agonists. Propofol itself, but not
      its fat emulsion, inhibits platelet aggregation and suppresses calcium
      mobilization. Extradural anaesthesia has been shown to prevent hypercoagulability
      during the perioperative period. Aprotinin reduces both blood loss and the
      incidence of blood transfusion during major orthopaedic and cardiac surgery.

PMID- 17013349
TI  - Context-sensitive half-time and anesthesia: how does theory match reality?
AB  - The pharmacokinetic model, which describes context-sensitive decrement times, has
      received validation through direct measurement. Further validation has come from
      the ability of targeted infusion schemes to obtain reliable and stable
      concentrations of a variety of intravenous drugs. A complete understanding of the
      concept will enable the appropriate selection of drugs and an appreciation of the
      strengths and limitations of current drug delivery systems.

PMID- 17013350
TI  - Postoperative shivering: aetiology and treatment.
AB  - Most postanaesthetic shivering-like tremor is normal thermoregulatory shivering
      in response to core hypothermia. Therefore, shivering will be prevented by
      maintaining intraoperative normothermia. Other thermoregulatory-related shivering
      is caused by the release of cytokines by the surgical procedure. Non
      thermoregulatory shivering, occurring in normothermic patients, is caused by
      other aetiologies such as postoperative pain. It is thus likely that adequate
      treatment of postoperative pain will ameliorate non-thermoregulatory tremor. In
      addition, the administration of antipyretic drugs reduces shivering in patients
      after cardiopulmonary bypass surgery.

PMID- 17013351
TI  - Carbon dioxide absorption: toxicity from sevoflurane and desflurane.
AB  - The degradation of volatile anaesthetics by desiccated carbon dioxide absorbents
      can result in adverse outcomes. Desiccated carbon dioxide absorbent reacting with
      desflurane can cause potentially life-threatening intraoperative carbon monoxide
      exposure; the reaction with sevoflurane can cause the formation of several toxic
      breakdown products, e.g. compound A. Compound A-related renal toxicity in humans
      is still a matter of controversy.

PMID- 17013353
TI  - Combining non-depolarizing neuromuscular blocking agents: synergism, addition or
      antagonism?
AB  - As the quality of currently available relaxants has improved, the need to combine
      relaxants to minimize the incidence and severity of their side-effects has
      decreased. Little work has been done in the past year characterizing the effects
      of combining different non-depolarizing neuromuscular blocking agents. That which
      has been done sheds some light on the nature of their interactions.

PMID- 17013352
TI  - Nitrous oxide: still useful in the year 2000?
AB  - The risk-benefit ratio of using nitrous oxide has been debated for many years. In
      this article the adverse effects of nitrous oxide on patient well-being,
      including its role in postoperative nausea and vomiting, its toxic effects and
      adverse physiological changes are reviewed. Guidelines for the rational use of
      the drug are suggested.

PMID- 17013354
TI  - New hemoglobin substitutes.
AB  - Blood transfusion is an essential and ubiquitous component of medical therapy.
      Despite careful screening and processing, allogeneic blood still carries a small
      but definable risk of the transmission of severe viral disease and the induction
      of immunological reactions. The logistics of its storage and transport continue
      to present a challenge, and its dependence on human donors will always keep it a
      scarce resource. It is not surprising that in the latter half of the 20th century
      efforts to develop blood substitutes have gained increasing momentum.

PMID- 17013355
TI  - Current world literature.

PMID- 17013356
TI  - Relief of low back pain immediately after acupuncture treatment--a randomised,
      placebo controlled trial.
AB  - BACKGROUND: The purpose of this study was to examine the immediate effect of
      single acupuncture stimulation to the most painful point in patients with low
      back pain. METHOD: A randomised, evaluator-blinded, sham controlled clinical
      trial was conducted in which 31 patients with low back pain were randomly
      allocated to either an acupuncture group (n = 15) or a sham acupuncture group (n
      = 16). Both acupuncture and sham acupuncture were performed at the most painful
      point on the lower back of the subjects. For the acupuncture group, a stainless
      steel needle was inserted to a depth of 20 mm and manually stimulated (sparrow
      pecking method) for 20 seconds, while for the sham treatment a guide tube without
      a needle was placed at the point and tapped on the skin. Changes in low back pain
      were evaluated with a visual analogue scale (VAS) and the Schober test.
      Participants were also asked if they felt the needling sensation or not. The
      therapy and the evaluation were independently performed by two different
      acupuncturists. RESULTS: VAS score and the Schober test score showed significant
      improvement after treatment as compared with the sham group (P = 0.02, 0.001,
      respectively). There were no significant differences in the needling sensation
      between the acupuncture and sham group. CONCLUSION: These results suggest that
      acupuncture at the most painful point gives immediate relief of low back pain.

PMID- 17013357
TI  - Aspects of pain, its assessment and evaluation from an acupuncture perspective.
AB  - Pain is a major clinical problem that causes great suffering for the individual
      and incurs costs for society. Accurate assessment and evaluation of perceived
      pain is necessary for diagnosis, for choice of treatment, and for the evaluation
      of treatment efficacy. The assessment of an individual's pain is a challenge
      since pain is a subjective, multidimensional experience, and assessment is based
      on the person's own self-report. The results are often varied, possibly due to
      inter-individual variation, but also in relation to gender and aetiology. A gold
      standard for pain assessment is still lacking, but rating scales, questionnaires,
      and methods derived from psychophysical concepts, such as threshold assessments
      and perceptual matching, are used. In the evaluation of pain and associated
      variables, both systematic and individual variation should be taken into account,
      as should pain-associated symptoms. Recommendations for pain treatment should be
      based on the patient's specific needs. Therefore, it is important to assess the
      level of perceived pain taking individual variation into account. The methods
      used should preferably have proved to be useful in randomised controlled trials,
      and analysis of pain assessment should consider its non-metric properties. In the
      future, the use of studies with a naturalistic protocol together with individual
      assessment of individual pain responses could increase the internal and external
      validity.

PMID- 17013358
TI  - Point specificity of acupuncture in the light of recent clinical and imaging
      studies.
AB  - One fundamental question that is still not resolved is whether acupuncture
      needles must be inserted in specific points to have their greatest effects. In
      the majority of large RCTs recently conducted in Germany, acupuncture was
      significantly more effective than doing nothing but not than sham acupuncture.
      Only for one study of chronic knee pain was acupuncture superior to sham. Brain
      imaging with functional magnetic resonance (fMRI) and positron emission
      tomography (PET) may be helpful but is still in its early stages. Several studies
      have shown differences between the way the deep central areas of the brain
      respond to genuine acupuncture compared with sham. Acupuncture can clearly
      produce complex changes that are relevant to pain transmission and perception,
      though it is still uncertain how specific these are. Similar changes have been
      seen after the application of placebo cream and after hypnosis. A previous paper
      discussed the likely central role of the limbic system in acupuncture, evidenced
      by euphoria and out of body experiences. There may be a good deal of common
      ground between acupuncture, placebo treatments, hypnosis, and even manipulative
      treatments. This understanding could offer a way out of the sterile debate about
      whether acupuncture is merely a placebo: acupuncture could be one effective way
      of stimulating responses within these deep areas of the brain, though not the
      only way.

PMID- 17013359
TI  - Electronic publishing and Acupuncture in Medicine.
AB  - The internet has fundamentally altered scientific publishing; this article
      discusses current models and how they affect this journal. The greatest
      innovation is a new range of open access journals published only on the internet,
      aimed at rapid publication and universal access. In most cases authors pay a
      publication charge for the overhead costs of the journal. Journals that are
      published by professional organisations primarily for their members have some
      functions other than publishing research, including clinical articles, conference
      reports and news items. A small number of these journals are permitting open
      access to their research reports. Commercial science publishing still exists,
      where profit for shareholders provides motivation in addition to the desire to
      spread knowledge for the benefit of all. A range of electronic databases now
      exists that offer various levels of listing and searching. Some databases provide
      direct links to journal articles, such as the LinkOut scheme in PubMed.
      Acupuncture in Medicine will continue to publish in paper format; all research
      articles will be available on open access, but non-subscribers will need to pay
      for certain other articles for the first 12 months after publication. All
      Acupuncture in Medicine articles will in future be included in the LinkOut
      scheme, and be presented to the databases electronically.

PMID- 17013360
TI  - Acupuncture for central pain affecting the ribcage following traumatic brain
      injury and rib fractures--a case report.
AB  - This case report describes the use of acupuncture in the management of chronic
      central pain in a 51 year old man following severe traumatic brain injury and
      multiple injuries including rib fractures. The patient reported rapid and
      significant improvements in pain and mood during a course of acupuncture
      treatment. Chronic pain following traumatic brain injury is a significant
      problem. Chronic pain after rib fractures is also commonly reported. Acupuncture
      is widely used in the management of pain but its use has been reported rarely in
      the traumatic brain injury literature. This case report suggests that acupuncture
      may be a useful option to consider in these patients. Outcome was assessed
      formally using a 0-10 verbal numerical rating scale for pain, and the Hospital
      Anxiety and Depression Scale (HADS) for psychological status before and after the
      course of treatment. These scales are widely used in clinical practice as well as
      in research involving patients with traumatic brain injury, although they have
      not been validated in this population. The changes in this patient's outcome
      scores were not consistent with the benefits he reported. Treatment of this
      patient highlighted the difficulties of using standardised self rating scales for
      patients with cognitive impairment. The report also discusses the effects of
      acupuncture on this patient's mood.

PMID- 17013361
TI  - Pedicle torsion of ovarian cyst and acupuncture--a case report.
AB  - A case history is reported of a patient who presented with acute pedicle torsion
      in a left ovarian cyst, which had been diagnosed seven months previously. The
      diagnosis was established by sonography. She declined surgery for personal
      reasons, and was treated with acupuncture. Her pain was successfully relieved,
      and she continued to be observed. The acupuncture was repeated daily for 15 days,
      after which time repeat sonography showed reduction in size of the cyst, and no
      torsion of the pedicle. No relapse had occurred at 16 months follow up.

PMID- 17013362
TI  - Mirror image contralateral pain reproduction--other cases.

PMID- 17013363
TI  - [Mitochondria and cell death].
AB  - In living cells, apoptosis is effected through many different pathways.
      Programmed cell death (PCD) may proceed with the involvement of membrane
      receptors, mitochondria, granzyme B, or the endoplasmic reticulum. The
      mitochondrial pathway is initiated from within the cell as a consequence of
      changes in reductive potential. It may also be caused by DNA mutation or various
      disturbances in the cell's metabolism. In some cases, the intrinsic pathway is
      connected with the extrinsic one, generated by the cell's environment. The
      central organelle which initiates the intrinsic pathway is the mitochondrion.
      Changes in the permeability of the mitochondrial outer membrane cause an outflow
      of cytochrom c, which interacts with cytoplasmic factor Apaf-1 and procaspase 9,
      in the presence of ATP, and thus triggers the caspase cascade. Apart from
      cytochrom c, more than 40 regular or executor particles involved in apoptosis
      might be released from the mitochondrion. These include Smac/DIABLO, Omi/HTR A2,
      endonuclease G, AIF, and IAP. Moreover, regulatory functions are performed by Bcl
      2 family proteins present in the cytoplasm that affect mitochondrial membrane
      permeability and by heat shock proteins (HSPs), both of these regulating caspase
      function. The phenomenon of programmed cell death is the main subject of research
      for many groups of scientists. There are still many aspects which need to be
      elucidated.

PMID- 17013364
TI  - [The role of leptin in the development of hypertension].
AB  - Leptin, the product the ob gene, is secreted by adipocytes to regulate energy
      homeostasis. This hormone may have an important influence on blood pressure,
      leading to hypertension. Leptin, acting in the hypothalamic melanocortin system,
      can activate or inactivate neuropeptides and produce hypertension, mainly by
      renal, adrenal, and muscular sympathoactivation. The role of leptin in regulating
      cardiovascular function in obesity is presented based on contemporary literature.
      Both intracellular signaling pathways activated by leptin and the role of leptin
      receptors are also discussed. The roles of endogens, neuropeptides in food
      intake, and energy expenditure are also presented.

PMID- 17013365
TI  - [Mechanisms of metastasis and molecular markers of malignant tumor progression.
      I. Colorectal cancer].
AB  - The ability of neoplastic cells to dissemination from a primary tumor to
      lymphatic nodes and to adjacent and distant tissues and organs is an inseparable
      feature of malignant tumors and the main cause of failure in their treatment.
      Metastasis formation is a multistage process which includes proteolysis, the
      motility and migration of cells, proliferation, and neoangiogenesis. In the first
      step, the cells released from the primary tumor have to penetrate to the blood or
      lymphatic vessels (intravasation), the road which dissemination follows.
      Circulating cells can then migrate through the walls of vessels to surrounding
      tissues (extravasation) where they settle, proliferate, and induce angiogenesis,
      creating metastases. Indispensable in the process of intra- and extravasation is
      the activation of proteolytic enzymes capable of degrading the extracellular
      matrix (ECM) surrounding the endothelium or creating the basement membrane of
      epithelial tissue in different organs. In this stage, the activation of
      proteolytic enzymes, such as proteinases of the plasmin system, serine
      proteinases, and matrix metalloproteinases (MMPs), is necessary. Simultaneously,
      changes occur in the expression of many superficial glycoproteins and factors
      responsible for cell adhesion (integrins) and intercellular communication
      (cadherins). Neoangiogenesis is connected with the expression of many markers of
      this process, among them vascular endothelial growth factor (VEGF), endoglin
      (CD105), a transmembranous glycoprotein which is a component of the receptor for
      transforming growth factor beta (TGFbeta), as well as neuropilin (NRP), the co
      receptor for VEGF. Conventionally, the prognosis of neoplastic disease and its
      treatment are based mainly on exact clinical and histopathological staging. This
      prognosis could, however, be improved by measuring the molecular and cellular
      markers which play key roles in tumor progression. Understanding the cellular
      processes responsible for tumor dissemination can be useful not only in the
      diagnosis and prognosis of treatment results, but also in developing targeted
      drugs, selectively directed towards those factors responsible for tumor
      invasiveness, as well as in creating new therapeutic strategies permitting the
      use of such drugs. In the present review the authors concentrate mainly on one
      tumor type, colorectal carcinoma, in which distant metastases, predominantly to
      the liver, are the main cause of failure, in spite of surgical curing of the
      primary tumor.

PMID- 17013366
TI  - [The role of RANK/RANKL and OPG in multiple myeloma].
AB  - Multiple myeloma (MM) almost exclusively develops in the bone marrow and
      generates devastating bone destruction by osteoclasts (OCs) recruited around
      myeloma cells. The severity of bone disease correlates with tumor burden. The
      interaction between RANK, expressed on the surface of OCs, and RANKL, a key
      molecule in the regulation of osteoclastogenesis expressed on bone marrow stromal
      cells, plays a role in the development and activation of OCs, whereas OPG, a
      decoy receptor for RANKL secreted from stromal cells, inhibits RANKL/RANK
      signaling. Myeloma cells stimulate osteoclastogenesis by triggering an increase
      in RANKL and decrease in OPG in bone marrow cells. They also express syndecan-1,
      a molecule which binds and stimulates OPG degradation in myeloma cells. MM cells
      can themselves express RANKL which can interact directly with RANK on OCs to
      promote osteoclast formation in a stromal cell-independent manner. Moreover,
      myeloma cells may additionally inhibit osteoblastogenesis directly or indirectly.
      The mechanisms involved in these coordinated processes are described and
      discussed.

PMID- 17013367
TI  - [Arginine as a crucial amino acid in carcinogenesis and tumor growth].
AB  - Arginine, a cationic semi-essential amino acid, is involved in numerous pathways
      of human metabolism. It serves as a precursor for the biosynthesis of proteins
      and also of ornithine, polyamines, nitric oxide, proline, glutamate, glutamine,
      creatine, agmatine and dimethylarginines. Arginine is conditionally essential
      amino acid as it is necessary under phase of growth (in children) and in adults
      under some pathological conditions, as well as during recovery after catabolic
      diseases. There is a growing interest in the role of arginine in cancerogenesis,
      since this amino acid has turned out to be absolutely essential for growth of
      neoplastic cells. It also plays a crucial role in biosynthetic pathways that
      significantly influence carcinogenesis and tumor biology. They include synthesis
      of polyamines and nitric oxide, important molecules, which may be synthesized
      solely from arginine. These findings have resulted in first clinical trials on
      arginine deprivation in therapy of some arginine-dependent (auxotrophic) tumors.
      The present article is focused on recently recognised role of arginine in tumor
      development, including processes associated with carcinogenesis, such as
      apoptosis and angiogenesis.

PMID- 17013368
TI  - [Tyrosine kinase inhibitors in the therapy of chronic myeloid leukaemia].
AB  - Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic
      stem cells resulting in increased myeloid and erythroid cells and platelets, and
      marked hyperplasia in the bone marrow. The natural history of CML is progression
      from a benign chronic phase, often through an accelerated phase, to a rapidly
      fatal blast crisis within 3-5 years. The constitutively activated ABL tyrosine
      kinase domain of the chimeric BCR-ABL oncoprotein is responsible for the
      transformation of hematopoietic stem cells and the symptoms of CML. Imatinib
      mesylate (Glivec), a specific small-molecule inhibitor of BCR-ABL, has become the
      standard drug therapy in all phases of the disease. Imatinib has greatly improved
      the outcome for patients with CML. Unfortunately, mutations causing resistance to
      imatinib are leading to relapse in some patients. Considerable progress has
      recently been made in understanding the structural biology of ABL and the
      molecular basis for resistance, facilitating the discovery and development of
      second- generation drugs designed to combat mutant forms of BCR-ABL. The first of
      these compounds to enter clinical development were dasatinib (BMS-354825) and
      AMN107 and, from phase I results, both of these promise a breakthrough in the
      treatment of imatinib-resistant CML.

PMID- 17013369
TI  - [Utility of axial images in an early Alzheimer disease diagnosis support system
      (VSRAD)].
AB  - In recent years, voxel-based morphometry (VBM) has become a popular tool for the
      early diagnosis of Alzheimer disease. The Voxel-Based Specific Regional Analysis
      System for Alzheimer's Disease (VSRAD), a VBM system that uses MRI, has been
      reported to be clinically useful. The able-bodied person database (DB) of VSRAD,
      which employs sagittal plane imaging, is not suitable for analysis by axial plane
      imaging. However, axial plane imaging is useful for avoiding motion artifacts
      from the eyeball. Therefore, we created an able-bodied person DB by axial plane
      imaging and examined its utility. We also analyzed groups of able-bodied persons
      and persons with dementia by axial plane imaging and reviewed the validity. After
      using the DB of axial plane imaging, the Z-score of the intrahippocampal region
      improved by 8 in 13 instances. In all brains, the Z-score improved by 13 in all
      instances.

PMID- 17013370
TI  - [Experimental study of coil selection considered from subject size].
AB  - We examined the index of coil selection in consideration of subject size to
      measure signal-to-noise ratio (SNR) and uniformity in a phantom experiment. The
      QD-Head, 8-channel-Head, and 8-channel-Head-Neck coil were used for head
      examination, QD-Body, 4-channel-TORSO, and 8-channel-Body coil were used for body
      examination. In the examination of the head, measurements were performed at
      various positions in a coil. The SNR measured by the QD-Head coil showed the
      highest values for 9 cm or 12 cm diameters of the phantom, and 10 cm to 15 cm
      distance from the coil entrance. The QD-Head coil also showed adequate uniformity
      at most sizes of phantoms. In the body examination, both multi-channel coils
      showed an SNR higher than the QD-Body coil for all sizes, but they were inferior
      to the QD-Body coil in uniformity. The 4-channel-TORSO coil showed an SNR higher
      than the 8-channel-Body coil when a phantom with a diameter of 21 cm or less was
      used. Since sensitivity distributions differ according to various cases, the 8
      channel coil does not necessarily always show a high SNR. It is necessary to
      perform coil selection according to the subject's size and purpose.

PMID- 17013371
TI  - [Examination of an imaging method in early Alzheimer disease diagnosis support
      system (VSRAD)].
AB  - The use of voxel-based morphometry (VBM) has recently become a popular tool for
      the early diagnosis of Alzheimer disease. The Voxel-Based Specific Regional
      Analysis System for Alzheimer's Disease (VSRAD) is a clinically useful VBM that
      employs MRI. However, there has been insufficient information about the influence
      of the image pickup apparatus and imaging conditions in terms of the value
      calculated by the sensitivity correction. We therefore reviewed this problem in a
      volunteer who provided consent. We were able to confirm reproducibility under the
      same conditions. When changing the image pickup apparatus and conditions, the
      average Z-score of 0.18+/-0.21 became larger, and the change in Z-score increased
      when imaging was done in the axial plane. Further, the average Z-score of 0.06+/
      0.21 for sensitivity correction use was high on average by 0.19+/-0.16 for phased
      array uniformity enhancement (PURE) and low for surface coil intensity correction
      (SCIC).

PMID- 17013372
TI  - [A new method for eliminating scatter components from a digital X-ray image by
      later processing].
AB  - The anti-scatter grid is generally used as a way of eliminating scattered
      radiation from X-ray photographs. This does not change even if the detector
      system changes from an analogue system to a digital system such as the flat-panel
      detector. We developed a new method that uses software to eliminate scatter
      components from digital X-ray images taken without the use of an anti-scatter
      grid. With this software, scatter components are eliminated from the X-ray image
      according to primary-to-scatter ratios, which were calculated on the basis of an
      imaginary phantom constructed by the pixel value of the X-ray image and on the
      spectrum of irradiated X-rays. In a trial calculation using a simulation image,
      it was confirmed that scatter components are eliminated at a high rate that is
      generally constant on the whole, irrespective of the kind and presence of the
      inhomogeneous region. When using this technique, the amount of X-ray exposure to
      a patient can be substantially reduced compared with that of radiography using
      the anti-scatter grid. Subsequently, the patient dose can be reduced.

PMID- 17013373
TI  - Histopathological alterations in irritable bowel syndrome.
AB  - Irritable bowel syndrome is a common disorder defined by a symptom complex
      including abdominal pain and altered bowel habit. The etiopathogenesis appears to
      be multifactorial and to involve altered gastrointestinal motor function,
      enhanced perception of visceral stimuli and psychosocial factors. More recently a
      role for mucosal immune activation has been suggested. Routine histologic
      examination reveals no mucosal abnormality in the majority of cases but
      quantitative histological, immunohistochemical and ultrastructural analyses
      reveal subtle morphologic changes involving lymphocytes, mast cells,
      enterochromaffin cells and enteric nerves. The recent appreciation of these
      changes has led to new hypotheses linking central and enteric nervous systems to
      immune processes. This review highlights the spectrum of morphologic changes that
      occur in irritable bowel syndrome, examines their relationship to the
      pathophysiology of irritable bowel syndrome and considers their relevance to
      daily pathology practice.

PMID- 17013374
TI  - Analyzing proteome topology and function by automated multidimensional
      fluorescence microscopy.
AB  - Temporal and spatial regulation of proteins contributes to function. We describe
      a multidimensional microscopic robot technology for high-throughput protein
      colocalization studies that runs cycles of fluorescence tagging, imaging and
      bleaching in situ. This technology combines three advances: a fluorescence
      technique capable of mapping hundreds of different proteins in one tissue section
      or cell sample; a method selecting the most prominent combinatorial molecular
      patterns by representing the data as binary vectors; and a system for imaging the
      distribution of these protein clusters in a so-called toponome map. By analyzing
      many cell and tissue types, we show that this approach reveals rules of
      hierarchical protein network organization, in which the frequency distribution of
      different protein clusters obeys Zipf's law, and state-specific lead proteins
      appear to control protein network topology and function. The technology may
      facilitate the development of diagnostics and targeted therapies.

PMID- 17013375
TI  - Protein chip fabrication by capture of nascent polypeptides.
AB  - The most challenging step in protein microarray fabrication is high-throughput
      production of proteins. Here we report two similar strategies to fabricate
      protein chips through capture onto a solid surface of the nascent polypeptides
      during translation of synthetic or in vitro-transcribed RNAs. Using these
      approaches, we efficiently fabricated both peptide and protein microarrays at
      relatively high density. We further demonstrated that such protein chips can be
      used to analyze protein activity.

PMID- 17013376
TI  - Control of Rad52 recombination activity by double-strand break-induced SUMO
      modification.
AB  - Homologous recombination is essential for genetic exchange, meiosis and error
      free repair of double-strand breaks. Central to this process is Rad52, a
      conserved homo-oligomeric ring-shaped protein, which mediates the exchange of the
      early recombination factor RPA by Rad51 and promotes strand annealing. Here, we
      report that Rad52 of Saccharomyces cerevisiae is modified by the ubiquitin-like
      protein SUMO, primarily at two sites that flank the conserved Rad52 domain.
      Sumoylation is induced on DNA damage and triggered by Mre11-Rad50-Xrs2 (MRX)
      complex-governed double-strand breaks (DSBs). Although sumoylation-defective
      Rad52 is largely recombination proficient, mutant analysis revealed that the SUMO
      modification sustains Rad52 activity and concomitantly shelters the protein from
      accelerated proteasomal degradation. Furthermore, our data indicate that
      sumoylation becomes particularly relevant for those Rad52 molecules that are
      engaged in recombination.

PMID- 17013377
TI  - Molecular mechanisms of coupled monoubiquitination.
AB  - Many proteins contain ubiquitin-binding domains or motifs (UBDs), such as the UIM
      (ubiquitin-interacting motif) and are referred to as ubiquitin receptors.
      Ubiquitin receptors themselves are frequently monoubiquitinated by a process that
      requires the presence of a UBD and is referred to as coupled monoubiquitination.
      Using a UIM-containing protein, eps15, as a model, we show here that coupled
      monoubiquitination strictly depends on the ability of the UIM to bind to
      monoubiquitin (mUb). We found that the underlying molecular mechanism is based on
      interaction between the UIM and a ubiquitin ligase (E3), which has itself been
      modified by ubiquitination. Furthermore, we demonstrate that the in vivo
      ubiquitination of members of the Nedd4 family of E3 ligases correlates with their
      ability to monoubiquitinate eps15. Thus, our results clarify the mechanism of
      coupled monoubiquitination and identify the ubiquitination of E3 ligases as a
      critical determinant in this process.

PMID- 17013378
TI  - Quantitative analysis of the activation mechanism of the multicomponent growth
      factor receptor Ret.
AB  - Cytokines and growth factors signal by modulating the interactions between
      multiple receptor components to form an activated receptor complex. The
      quantitative details of the activation mechanisms of this important class of
      receptors are not well understood. Using receptor phosphorylation measurements in
      live cells, as well as mathematical modeling and data fitting, we have
      characterized the multistep mechanism by which the GDNF-family neurotrophin
      artemin (ART), together with its co-receptor GDNF-family receptor alpha3
      (GFRalpha3), brings about activation of the Ret receptor tyrosine kinase through
      formation of a pentameric signaling complex: ART-(GFRalpha3)(2)-(Ret)(2). By
      systematically varying the concentrations of ART and cell-surface GFRalpha3, we
      establish both the sequence of steps by which the signaling complex forms and the
      affinities of all the steps, including the two-dimensional affinities of the
      steps involving protein-protein interactions between membrane-bound species. Our
      results reveal the ways in which the individual binary interactions involved in
      the activation of a multicomponent receptor govern the receptor's functional
      properties.

PMID- 17013379
TI  - Dynamic shifts in the owl's auditory space map predict moving sound location.
AB  - The optic tectum of the barn owl contains a map of auditory space. We found that,
      in response to moving sounds, the locations of receptive fields that make up the
      map shifted toward the approaching sound. The magnitude of the receptive field
      shifts increased systematically with increasing stimulus velocity and, therefore,
      was appropriate to compensate for sensory and motor delays inherent to auditory
      orienting behavior. Thus, the auditory space map is not static, but shifts
      adaptively and dynamically in response to stimulus motion. We provide a
      computational model to account for these results. Because the model derives
      predictive responses from processes that are known to occur commonly in neural
      networks, we hypothesize that analogous predictive responses will be found to
      exist widely in the central nervous system. This hypothesis is consistent with
      perceptions of stimulus motion in humans for many sensory parameters.

PMID- 17013380
TI  - Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity.
AB  - We examined the contribution of 5-HT1A autoreceptors (with [11C]WAY100635
      positron emission tomography) to amygdala reactivity (with blood oxygenation
      level-dependent functional magnetic resonance imaging) in 20 healthy adult
      volunteers. We found a significant inverse relationship wherein 5-HT1A
      autoreceptor density predicted a notable 30-44% of the variability in amygdala
      reactivity. Our data suggest a potential molecular mechanism by which a reduced
      capacity for negative feedback regulation of 5-HT release is associated with
      increased amygdala reactivity.

PMID- 17013381
TI  - Local potassium signaling couples neuronal activity to vasodilation in the brain.
AB  - The mechanisms by which active neurons, via astrocytes, rapidly signal
      intracerebral arterioles to dilate remain obscure. Here we show that modest
      elevation of extracellular potassium (K+) activated inward rectifier K+ (Kir)
      channels and caused membrane potential hyperpolarization in smooth muscle cells
      (SMCs) of intracerebral arterioles and, in cortical brain slices, induced Kir
      dependent vasodilation and suppression of SMC intracellular calcium (Ca2+)
      oscillations. Neuronal activation induced a rapid (<2 s latency) vasodilation
      that was greatly reduced by Kir channel blockade and completely abrogated by
      concurrent cyclooxygenase inhibition. Astrocytic endfeet exhibited large
      conductance, Ca2+-sensitive K+ (BK) channel currents that could be activated by
      neuronal stimulation. Blocking BK channels or ablating the gene encoding these
      channels prevented neuronally induced vasodilation and suppression of arteriolar
      SMC Ca2+, without affecting the astrocytic Ca2+ elevation. These results support
      the concept of intercellular K+ channel-to-K+ channel signaling, through which
      neuronal activity in the form of an astrocytic Ca2+ signal is decoded by
      astrocytic BK channels, which locally release K+ into the perivascular space to
      activate SMC Kir channels and cause vasodilation.

PMID- 17013382
TI  - Nonblinking and long-lasting single-molecule fluorescence imaging.
AB  - Photobleaching and blinking of fluorophores pose fundamental limitations on the
      information content of single-molecule fluorescence measurements. Photoinduced
      blinking of Cy5 has hampered many previous investigations using this popular
      fluorophore. Here we show that Trolox in combination with the enzymatic oxygen
      scavenging system eliminates Cy5 blinking, dramatically reduces photobleaching
      and improves the signal linearity at high excitation rates, significantly
      extending the applicability of single-molecule fluorescence techniques.

PMID- 17013383
TI  - Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional
      insights and clinical implications.
AB  - Treatment of chronic myeloid leukemia (CML) with the tyrosine kinase inhibitor
      imatinib represents a successful application of molecularly targeted cancer
      therapy. A rapid hematologic and cytogenetic response can be induced in the
      majority of people, even in advanced disease. However, complete eradication of
      malignant cells, which are characterized by the expression of the BCR-ABL1 fusion
      protein, is rare. Reasons for the persistence of the malignant clone are
      currently not known and provide a substantial challenge for clinicians and
      biologists. Based on a mathematical modeling approach that quantitatively
      explains a broad range of phenomena, we show for two independent datasets that
      clinically observed BCR-ABL1 transcript dynamics during imatinib treatment of CML
      can consistently be explained by a selective functional effect of imatinib on
      proliferative leukemia stem cells. Our results suggest the general potential of
      imatinib to induce a complete elimination of the malignant clone. Moreover, we
      predict that the therapeutic benefit of imatinib can, under certain
      circumstances, be accelerated by combination with proliferation-stimulating
      treatment strategies.

PMID- 17013384
TI  - Quantifying viable virus-specific T cells without a priori knowledge of fine
      epitope specificity.
AB  - Identification of pathogen-specific T cells has been greatly facilitated by the
      advent of synthetic peptide-major histocompatibility complex (MHC) tetramers. In
      many cases, however, specific epitopes have not been defined, necessitating
      detection methods that function independently of exact peptide-MHC specificity.
      Lymphocytes acquire surface proteins from antigen-presenting cells (APCs), and we
      have exploited this phenomenon to develop the T-cell recognition of APCs by
      protein transfer (TRAP) assay. This method is based on biotinylation and
      streptavidin-fluorochrome labeling of APCs, followed by subsequent acquisition of
      this label by antigen-specific T cells. The TRAP procedure detects MHC class I
      restricted T cells regardless of their cytokine profiles or peptide-MHC
      affinities, and provides a versatile tool for monitoring the phenomenon of APC
      membrane acquisition by antigen-specific T cells.

PMID- 17013385
TI  - In vivo imaging of lymph node metastasis with telomerase-specific replication
      selective adenovirus.
AB  - Currently available methods for detection of tumors in vivo such as computed
      tomography and magnetic resonance imaging are not specific for tumors. Here we
      describe a new approach for visualizing tumors whose fluorescence can be detected
      using telomerase-specific replication-competent adenovirus expressing green
      fluorescent protein (GFP) (OBP-401). OBP-401 contains the replication cassette,
      in which the human telomerase reverse transcriptase (hTERT) promoter drives
      expression of E1 genes, and the GFP gene for monitoring viral replication. When
      OBP-401 was intratumorally injected into HT29 tumors orthotopically implanted
      into the rectum in BALB/c nu/nu mice, para-aortic lymph node metastasis could be
      visualized at laparotomy under a three-chip color cooled charged-coupled device
      camera. Our results indicate that OBP-401 causes viral spread into the regional
      lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP
      expression in metastatic lymph nodes. This technology is adaptable to detect
      lymph node metastasis in vivo as a preclinical model of surgical navigation.

PMID- 17013386
TI  - Rad4-Rad23 interaction with SWI/SNF links ATP-dependent chromatin remodeling with
      nucleotide excision repair.
AB  - Chromatin rearrangement occurs during nucleotide excision repair (NER). Here we
      show that Snf6 and Snf5, two subunits of the SWI/SNF chromatin-remodeling complex
      in Saccharomyces cerevisiae, copurify with the NER damage-recognition heterodimer
      Rad4-Rad23. This interaction between SWI/SNF and Rad4-Rad23 is stimulated by UV
      irradiation. We demonstrate that NER in the transcriptionally silent, nucleosome
      loaded HML locus is reduced in yeast cells lacking functional SWI/SNF. In
      addition, using a restriction enzyme accessibility assay, we observed UV-induced
      nucleosome rearrangement at the silent HML locus. Notably, this rearrangement is
      markedly attenuated when SWI/SNF is inactivated. These results indicate that the
      SWI/SNF chromatin-remodeling complex is recruited to DNA lesions by damage
      recognition proteins to increase DNA accessibility for NER in chromatin.

PMID- 17013387
TI  - Single-molecule observations of neck linker conformational changes in the kinesin
      motor protein.
AB  - Kinesin-1 is a dimeric motor protein that moves cargo processively along
      microtubules. Kinesin motility has been proposed to be driven by the coordinated
      forward extension of the neck linker (a approximately 12-residue peptide) in one
      motor domain and the rearward positioning of the neck linker in the partner motor
      domain. To test this model, we have introduced fluorescent dyes selectively into
      one subunit of the kinesin dimer and performed 'half-molecule' fluorescence
      resonance energy transfer to measure conformational changes of the neck linker.
      We show that when kinesin binds with both heads to the microtubule, the neck
      linkers in the rear and forward heads extend forward and backward, respectively.
      During ATP-driven motility, the neck linkers switch between these conformational
      states. These results support the notion that neck linker movements accompany the
      'hand-over-hand' motion of the two motor domains.

PMID- 17013388
TI  - A pathway regulated by cell cycle inhibitor p27Kip1 and checkpoint inhibitor
      Smad3 is involved in the induction of T cell tolerance.
AB  - Peripheral tolerance is essential for immunological homeostasis. Tolerant T cells
      are thought to arise after T cell receptor ligation in conditions that are
      nonpermissive for replication. Here we have investigated the function of the cell
      cycle inhibitor p27(Kip1) in tolerance induction in vivo using naive T cell
      receptor-transgenic cells lacking the cyclin-dependent kinase (Cdk)-binding
      domain of p27(Kip1)(p27delta). Wild-type but not p27delta cells underwent
      tolerization. Tolerized wild-type cells had impaired Cdk2 and Cdc2 kinase
      activity and failed to phosphorylate the checkpoint inhibitor Smad3, leading to
      enhanced expression of the Cdk inhibitor p15. In contrast, p27delta cells
      proliferated in tolerizing conditions because of Cdk kinase activation and
      phosphorylation of Smad3, which resulted in no upregulation of p15. Smad3
      'knockdown' prevented tolerance induction, whereas expression of a Smad3 mutant
      resistant to Cdk-mediated phosphorylation recapitulated molecular and functional
      events of tolerance. Thus, p27(Kip1) is required during induction of tolerance
      and Smad3 regulates T cell responses 'downstream' of p27(Kip1).

PMID- 17013389
TI  - A thymic pathway of mouse natural killer cell development characterized by
      expression of GATA-3 and CD127.
AB  - Natural killer (NK) cell development is thought to occur in the bone marrow. Here
      we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular
      markers of a pathway of mouse NK cell development that originates in the thymus.
      Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their
      homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK
      cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual
      functional attributes, including reduced cytotoxicity but considerable cytokine
      production. Those characteristics are reminiscent of human CD56(hi) CD16- NK
      cells, which we found expressed CD127 and had more GATA-3 expression than human
      CD56+ CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways
      generate distinct mouse NK cells with properties similar to those of the two
      human CD56 NK cell subsets.

PMID- 17013390
TI  - Individual stem cells with highly variable proliferation and self-renewal
      properties comprise the human hematopoietic stem cell compartment.
AB  - Hematopoiesis requires tight regulation of the hematopoietic stem cell (HSC)
      population; however, the dynamics of HSC use at steady state are uncertain. Over
      3-7 months, we evaluated the repopulation and self-renewal of more than 600
      individual human 'severe combined immunodeficiency mouse-repopulating cells'
      (SRCs), tracked on the basis of lentiviral integration sites, in serially
      transplanted immune-deficient mice, as well as of SRC daughter cells that
      migrated to different marrow locations in a single mouse. Our data demonstrate
      maintenance by self-renewing SRCs after an initial period of clonal instability,
      a result inconsistent with the clonal succession model. We found wide variation
      in proliferation kinetics and self-renewal among SRCs, as well as between SRC
      daughter cells that repopulated equivalently, suggesting that SRC fate is
      unpredictable before SRCs enter more rigid 'downstream' developmental programs.

PMID- 17013391
TI  - Apoptotic neutrophils and T cells sequester chemokines during immune response
      resolution through modulation of CCR5 expression.
AB  - During the resolution phase of inflammation, the 'corpses' of apoptotic
      leukocytes are gradually cleared by macrophages. Here we report that during the
      resolution of peritonitis, the CCR5 chemokine receptor ligands CCL3 and CCL5
      persisted in CCR5-deficient mice. CCR5 expression on apoptotic neutrophils and
      activated apoptotic T cells sequestered and effectively cleared CCL3 and CCL5
      from sites of inflammation. CCR5 expression on late apoptotic human
      polymorphonuclear cells was downregulated by proinflammatory stimuli, including
      tumor necrosis factor, and was upregulated by 'proresolution' lipid mediators,
      including lipoxin A4, resolvin E1 and protectin D1. Our results suggest that
      CCR5+ apoptotic leukocytes act as 'terminators' of chemokine signaling during the
      resolution of inflammation.

PMID- 17013392
TI  - Genome-wide analysis of estrogen receptor binding sites.
AB  - The estrogen receptor is the master transcriptional regulator of breast cancer
      phenotype and the archetype of a molecular therapeutic target. We mapped all
      estrogen receptor and RNA polymerase II binding sites on a genome-wide scale,
      identifying the authentic cis binding sites and target genes, in breast cancer
      cells. Combining this unique resource with gene expression data demonstrates
      distinct temporal mechanisms of estrogen-mediated gene regulation, particularly
      in the case of estrogen-suppressed genes. Furthermore, this resource has allowed
      the identification of cis-regulatory sites in previously unexplored regions of
      the genome and the cooperating transcription factors underlying estrogen
      signaling in breast cancer.

PMID- 17013393
TI  - Differences in reactive oxygen species production explain the phenotypes
      associated with common mouse mitochondrial DNA variants.
AB  - Common mitochondrial DNA (mtDNA) haplotypes in humans and mice have been
      associated with various phenotypes, including learning performance and disease
      penetrance. Notably, no influence of mtDNA haplotype in cell respiration has been
      demonstrated. Here, using cell lines carrying four different common mouse mtDNA
      haplotypes in an identical nuclear background, we show that the similar level of
      respiration among the cell lines is only apparent and is a consequence of
      compensatory mechanisms triggered by different production of reactive oxygen
      species. We observe that the respiration capacity per molecule of mtDNA in cells
      with the NIH3T3 or NZB mtDNA is lower than in those with the C57BL/6J, CBA/J or
      BALB/cJ mtDNA. In addition, we have determined the genetic element underlying
      these differences. Our data provide insight into the molecular basis of the
      complex phenotypes associated with common mtDNA variants and anticipate a
      relevant contribution of mtDNA single nucleotide polymorphisms to phenotypic
      variability in humans.

PMID- 17013394
TI  - Differentiated cells are more efficient than adult stem cells for cloning by
      somatic cell nuclear transfer.
AB  - Since the creation of Dolly via somatic cell nuclear transfer (SCNT), more than a
      dozen species of mammals have been cloned using this technology. One hypothesis
      for the limited success of cloning via SCNT (1%-5%) is that the clones are likely
      to be derived from adult stem cells. Support for this hypothesis comes from the
      findings that the reproductive cloning efficiency for embryonic stem cells is
      five to ten times higher than that for somatic cells as donors and that cloned
      pups cannot be produced directly from cloned embryos derived from differentiated
      B and T cells or neuronal cells. The question remains as to whether SCNT-derived
      animal clones can be derived from truly differentiated somatic cells. We tested
      this hypothesis with mouse hematopoietic cells at different differentiation
      stages: hematopoietic stem cells, progenitor cells and granulocytes. We found
      that cloning efficiency increases over the differentiation hierarchy, and
      terminally differentiated postmitotic granulocytes yield cloned pups with the
      greatest cloning efficiency.

PMID- 17013397
TI  - Glycan microarray technologies: tools to survey host specificity of influenza
      viruses.
AB  - New technologies are urgently required for rapid surveillance of the current H5N1
      avian influenza A outbreaks to gauge the potential for adaptation of the virus to
      the human population, a crucial step in the emergence of pandemic influenza virus
      strains. Owing to the species-specific nature of the interaction between the
      virus and host glycans, attention has recently focused on novel glycan array
      technologies that can rapidly assess virus receptor specificity and the potential
      emergence of human-adapted H5N1 viruses.

PMID- 17013396
TI  - Regulation of primary cilia formation and left-right patterning in zebrafish by a
      noncanonical Wnt signaling mediator, duboraya.
AB  - Primary cilia are microtubule-based organelles that project from the surface of
      nearly every animal cell. Although important functions of primary cilia in
      morphogenesis and tissue homeostasis have been identified, the mechanisms that
      control the formation of primary cilia are not understood. Here we characterize a
      zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis.
      Knockdown of dub in zebrafish embryos results in both defects in primary cilia
      formation in Kupffer's vesicle and randomization of left-right organ asymmetries.
      We show that, at the molecular level, the function of dub in ciliogenesis is
      regulated by phosphorylation, which in turn depends on Frizzled-2-mediated
      noncanonical Wnt signaling. We also provide evidence that, at the cellular level,
      dub function is essential for actin organization in the cells lining Kupffer's
      vesicle. Taken together, our findings identify a molecular factor that links
      noncanonical Wnt signaling with the control of left-right axis specification, and
      provide an entry point for analyzing the mechanisms that regulate primary cilia
      formation.

PMID- 17013395
TI  - Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked
      idiopathic congenital nystagmus.
AB  - Idiopathic congenital nystagmus is characterized by involuntary, periodic,
      predominantly horizontal oscillations of both eyes. We identified 22 mutations in
      FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of
      42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females)
      yielded three mutations (7%). We found restricted expression of FRMD7 in human
      embryonic brain and developing neural retina, suggesting a specific role in the
      control of eye movement and gaze stability.

PMID- 17013398
TI  - Not just a light story.

PMID- 17013399
TI  - Reform science? First, reset the economy.

PMID- 17013400
TI  - Italian science: greater expectations?

PMID- 17013401
TI  - The left hand of brightness: past, present and future of negative index
      materials.

PMID- 17013402
TI  - Beyond metamaterials.

PMID- 17013404
TI  - Hydrogels: DNA bulks up.

PMID- 17013405
TI  - Solid-state lighting: the benefit of disorder.

PMID- 17013406
TI  - Spintronics: gadolinium makes good spin contacts.

PMID- 17013407
TI  - Phononics: colloidal crystals go hypersonic.

PMID- 17013410
TI  - Diffractive imaging of nanoparticles on a substrate.

PMID- 17013409
TI  - Semiconductors: an empire of many dimensions.

PMID- 17013411
TI  - A new dawn in the land of the rising sun.

PMID- 17013412
TI  - Organizing cytoplasmic microtubules: no nucleus, no problem.

PMID- 17013413
TI  - HAUSP hunting the FOX(O).

PMID- 17013414
TI  - Atg5: more than an autophagy factor.

PMID- 17013415
TI  - How wandering cells make a perfect eye.

PMID- 17013416
TI  - Uncovering stemness.

PMID- 17013417
TI  - Kizuna takes pole position.

PMID- 17013418
TI  - Adherens junctions: which way is up?

PMID- 17013421
TI  - Human herpes virus-6 encephalitis in a paediatric bone marrow recipient:
      successful treatment with pharmacokinetic monitoring and high doses of
      ganciclovir.

PMID- 17013422
TI  - Epstein-Barr virus-associated haemophagocytic lympho-histiocytosis after stem
      cell transplantation.

PMID- 17013423
TI  - Allogeneic stem cell transplantation as treatment for myelofibrosis.
AB  - Idiopathic myelofibrosis (IMF) is a clonal disorder resulting from the
      proliferation of aberrant hematopoietic stem cells. Conventional treatment is
      unsatisfactory, and with the exception of supportive blood transfusions, none of
      the standard therapies have been shown to confer a survival advantage. Allogeneic
      stem cell transplantation represents the only treatment modality with proven
      curative potential. Myeloablative conditioning regimens are associated with high
      transplant-related mortality, particularly in the elderly, making most patients
      with IMF ineligible for this treatment. Strategies using reduced intensity
      conditioning regimes have allowed application of allogeneic transplantation to a
      broader range of patients and a number of recent reports have demonstrated
      potential efficacy.

PMID- 17013424
TI  - Comparative outcome of hematopoietic stem cell transplantation for pediatric
      acute lymphoblastic leukemia following cyclophosphamide and total body
      irradiation or VP16 and total body irradiation conditioning regimens.
AB  - To compare the outcome of hematopoietic stem cell transplantation (HSCT) in
      pediatric acute lymphoblastic leukemia (ALL) conditioned with two different
      regimens: (1) single dose of VP16 (60 mg/kg over 4 h) and total body irradiation
      (TBI; 1200 cGy, in six fractions) or (2) Cyclophosphamide 50 mg/kg over 1 h daily
      for 4 days followed by the same dose of TBI. One hundred and seven children with
      ALL received fully matched HSCT from 1990 to 2003 in the Hospital for Sick
      Children, Toronto. All received cyclosporin A and a short course of methotrexate
      for graft-versus-host disease (GVHD) prophylaxis. The VP16 group, there were 36
      matched related donor transplants (MRD) and 26 matched unrelated donor
      transplants (MUD), and in the cyclophosphamide group there were 23 MRD and 22 MUD
      transplants. Neutrophil engraftment occurred at a median of 18 and 17 days for
      the VP16/TBI and the CY/TBI groups, respectively. The 3 year event-free survival
      and overall survival were 47 +/- 7 and 55 +/- 7% for those receiving VP16/TBI,
      and 51 +/- 8 and 53 +/- 8% for the CY/TBI group. There were no significant
      differences in the prevalence of acute or chronic GVHD and transplant-related
      mortality between the two groups. Both VP16/FTBI and CY/FTBI regimen are equally
      effective regimens.

PMID- 17013425
TI  - Acute renal failure following myeloablative autologous and allogeneic
      hematopoietic cell transplantation.

PMID- 17013426
TI  - Stem cell transplantation for the Wiskott-Aldrich syndrome: a single-center
      experience confirms efficacy of matched unrelated donor transplantation.
AB  - The treatment of Wiskott-Aldrich syndrome (WAS), a once uniformly fatal disorder,
      has evolved considerably as the use of hematopoietic stem cell transplant has
      become more widespread. For the majority of patients who lack an human leukocyte
      antigen-identical sibling, closely matched unrelated donor bone marrow transplant
      (MUD BMT) at an early age is an excellent option that nevertheless is not
      uniformly chosen. We retrospectively analyzed our experience with transplantation
      in 23 patients with WAS from 1990 to 2005 at the University of Brescia, Italy, of
      whom 16 received MUD BMT. Myeloablative chemotherapy was well tolerated with
      median neutrophil engraftment at day 18, and no cases of grade III or IV graft-vs
      host disease. Overall survival was very good with 78.2% (18/23) of the whole
      cohort and 81.2% (13/16) of MUD BMT recipients surviving. Among 18 survivors,
      full donor engraftment was detected in 12 patients, and stable mixed chimerism in
      all blood lineages in four patients. Deaths were limited to patients who had
      received mismatched related BMT or who had severe clinical symptomatology at the
      time of transplantation, further emphasizing the safety and efficacy of MUD BMT
      when performed early in the clinical course of WAS.

PMID- 17013427
TI  - Nonmyeloablative stem cell transplantation for nonmalignant diseases in children
      with severe organ dysfunction.
AB  - Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases
      in children. However, patients frequently have significant morbidity before
      transplantation and there is a high transplant-related mortality.
      Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six
      pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from
      different stem cell sources. All patients were conditioned with
      fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical
      grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of
      tacrolimus and methotrexate with additional prednisolone for haploidentical
      grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All
      patients had severe organ dysfunction that precluded transplantation with
      conventional conditioning. Five of the six are alive and in complete disease
      resolution at a median of 19 months (range, 7-53 months) after SCT. One patient
      died of bacteremia before engraftment. Three patients achieved complete donor
      chimerism. Two patients remained stable mixed chimerism. Short-term toxicities
      were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine
      based nonmyeloablative regimen followed by SCT provides a good approach for
      children with nonmalignant diseases. Even patients with severe organ dysfunctions
      had adequate engraftment with acceptable toxicities.

PMID- 17013428
TI  - Synergistic effects of injection of bone marrow cells into both portal vein and
      bone marrow on tolerance induction in transplantation of allogeneic pancreatic
      islets.
AB  - We have established a new method for allogeneic pancreatic islet (PI)
      transplantation: relatively low doses of irradiation followed by simultaneous
      transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In
      the present study, we have compared this method with intra-bone marrow (IBM)-bone
      marrow transplantation (BMT), and with a combination of both methods.
      Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 (F344, RT1A(l),
      RT1B(l)), were irradiated 1 day before transplantation. PIs of Brown Norway rats
      (BN, RT1A(n), RT1B(n)) were transplanted into the liver of the diabetic F344 rats
      via the PV. BMCs from BN rats were injected into the recipients' bone marrow
      (IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM
      (PV+IBM). We compared graft survival among the groups of '9 Gy+IBM'(10/10
      accepted), '9 Gy+PV'(7/10 accepted), '9 Gy+IV'(0/7 accepted), '9 Gy+PV+IBM'(8/8
      accepted), '8.5 Gy+IBM'(4/9 accepted), '8.5 Gy+PV'(0/7 accepted), '8.5 Gy+IV'(0/7
      accepted), '8.5 Gy+PV+IBM'(9/12 accepted), '8 Gy+IBM'(2/10 accepted) and '8
      Gy+PV+IBM'(2/8 accepted). As we reported previously, PV-BMT is more effective in
      inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires
      less pretreatment than PV-BMT. (PV+IBM)-BMT was found to be the most effective in
      inducing the acceptance of allogeneic PIs. These results suggest that allogeneic
      PI-transplantation in conjunction with (PV+IBM)-BMT could become a viable
      strategy.

PMID- 17013429
TI  - The effects on saturated fat purchases of providing internet shoppers with
      purchase- specific dietary advice: a randomised trial.
AB  - OBJECTIVES: The supermarket industry now services many customers through online
      food shopping over the Internet. The Internet shopping process offers a novel
      opportunity for the modification of dietary patterns. The aim of this study was
      to evaluate the effects on consumers' purchases of saturated fat of a fully
      automated computerised system that provided real-time advice tailored to the
      consumers' specific purchases recommending foods lower in saturated fat. DESIGN:
      This study was a blinded, randomised controlled trial. SETTING: The study was
      conducted in Sydney, New South Wales, Australia. PARTICIPANTS: The participants
      were consumers using a commercial online Internet shopping site between February
      and June 2004. INTERVENTIONS: Individuals assigned to intervention received fully
      automated advice that recommended specific switches from selected products higher
      in saturated fat to alternate similar products lower in saturated fat.
      Participants assigned to control received general non-specific advice about how
      to eat a diet lower in saturated fat. OUTCOME MEASURES: The outcome measure was
      the difference in saturated fat (grams per 100 g of food) in shopping baskets
      between the intervention and control groups. RESULTS: There were 497 randomised
      participants, mean age 40 y, each shopping for an average of about three people.
      The amount of saturated fat in the foods purchased by the intervention group was
      0.66% lower (95% confidence interval 0.48-0.84, p < 0.001) than in the control
      group. The effects of the intervention were sustained over consecutive shopping
      episodes, and there was no difference in the average cost of the food bought by
      each group. CONCLUSIONS: Fully automated, purchase-specific dietary advice
      offered to customers during Internet shopping can bring about changes in food
      purchasing habits that are likely to have significant public health implications.
      Because implementation is simple to initiate and maintain, this strategy would
      likely be highly cost-effective.

PMID- 17013431
TI  - Gametocytaemia after drug treatment of asymptomatic Plasmodium falciparum.
AB  - OBJECTIVES: Treatment of Plasmodium falciparum malaria with sulfadoxine
      pyrimethamine (SP) is followed by a sharp rise in the prevalence and density of
      gametocytes. We did a randomized trial to determine the effect of treatment of
      asymptomatic infections with SP or SP plus one dose of artesunate (SP+AS) on
      gametocyte carriage. DESIGN: The study was a three-arm open-label randomized
      trial. We randomized asymptomatic carriers of P. falciparum to receive
      antimalarial treatment or placebo, and recorded the prevalence and density of
      gametocytes over the next 2 mo. SETTING: The trial was conducted during the dry
      (low malaria transmission) season in four rural villages in Gambia. PARTICIPANTS:
      Participants were adults and children aged over 6 mo with asexual P. falciparum
      infection and confirmed free of clinical symptoms of malaria over a 2-d screening
      period. INTERVENTIONS: Participants were randomized to receive a single dose of
      SP or SP+AS or placebo. OUTCOME MEASURES: The outcome measures were the presence
      of gametocytes 7 and 56 d after treatment, and the duration and density of
      gametocytaemia over 2 mo. RESULTS: In total, 372 asymptomatic carriers were
      randomized. Gametocyte prevalence on day 7 was 10.5% in the placebo group, 11.2%
      in the SP group (risk difference to placebo 0.7%, 95% confidence interval -7.4%
      to 8.7%, p = 0.87), and 7.1% in the SP+AS group (risk difference to placebo 4.1%,
      95% confidence interval -3.3% to 12%, p = 0.28). By day 56, gametocyte prevalence
      was 13% in the placebo group and 2% in both drug-treated groups. Gametocyte
      carriage (the area under the curve of gametocyte density versus time), was
      reduced by 71% in the SP group, and by 74% in the SP+AS group, compared to
      placebo. Gametocyte carriage varied with age and was greater among children under
      15 than among adults. CONCLUSIONS: Treatment of asymptomatic carriers of P.
      falciparum with SP does not increase gametocyte carriage or density. Effective
      treatment of asexual parasitaemia in the dry season reduces gametocyte carriage
      to very low levels after 4 wk.

PMID- 17013430
TI  - Long-term impact of malaria chemoprophylaxis on cognitive abilities and
      educational attainment: follow-up of a controlled trial.
AB  - OBJECTIVES: We investigated the long-term impact of early childhood malaria
      prophylaxis on cognitive and educational outcomes. DESIGN: This was a household
      based cluster-controlled intervention trial. SETTING: The study was conducted in
      15 villages situated between 32 km to the east and 22 km to the west of the town
      of Farafenni, the Gambia, on the north bank of the River Gambia. PARTICIPANTS: A
      total of 1,190 children aged 3-59 mo took part in the trial. We traced 579 trial
      participants (291 in the prophylaxis group and 288 in the placebo group) in 2001,
      when their median age was 17 y 1 mo (range 14 y 9 mo to 19 y 6 mo).
      INTERVENTIONS: Participants received malaria chemoprophylaxis
      (dapsone/pyrimethamine) or placebo for between one and three malaria transmission
      seasons from 1985 to 1987 during the controlled trial. At the end of the trial,
      prophylaxis was provided for all children under 5 y of age living in the study
      villages. OUTCOME MEASURES: The outcome measures were cognitive abilities, school
      enrolment, and educational attainment (highest grade reached at school). RESULTS:
      There was no significant overall intervention effect on cognitive abilities, but
      there was a significant interaction between intervention group and the duration
      of post-trial prophylaxis (p = 0.034), with cognitive ability somewhat higher in
      the intervention group among children who received no post-trial prophylaxis
      (treatment effect = 0.2 standard deviations [SD], 95% confidence interval [CI] 
      0.03 to 0.5) and among children who received less than 1 y of post-trial
      prophylaxis (treatment effect = 0.4 SD, 95% CI 0.1 to 0.8). The intervention
      group had higher educational attainment by 0.52 grades (95% CI = -0.041 to 1.089;
      p = 0.069). School enrolment was similar in the two groups. CONCLUSIONS: The
      results are suggestive of a long-term effect of malaria prophylaxis on cognitive
      function and educational attainment, but confirmatory studies are needed.

PMID- 17013432
TI  - [Metabolic syndrome in inflammatory rheumatic diseases].
AB  - Toward the end of the last century a better knowledge of cardiovascular (CV) risk
      factors and their associations led investigators to propose the existence of a
      unique pathophysiological condition called "metabolic" or "insulin resistance
      syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are
      considered its most important treatment targets. Different definitions have been
      provided by World Health Organization (WHO) and by The Third Report of The
      National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In
      particular, abdominal obesity, hypertension, low HDL cholesterol and
      hyperglicemia are the most common items used for its definition. The presence of
      MetS is effective in predicting the future risk of diabetes and coronaropathies.
      The evidence of a higher CV risk rate among different rheumatic inflammatory
      diseases has recently been associated with high prevalence of MetS in some cases.
      Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas
      systemic lupus erythematosus among connective tissue disorders. This review
      analyses all most important studies about the evidence of MetS in rheumatic
      patients and the main clinical and prognostic significance of this relation.

PMID- 17013433
TI  - [Neuropsychiatric lupus erythematosus].
AB  - Neuropsychiatric involvement in patients with Systemic Lupus Erythematosus (SLE),
      first mentioned by Kaposi more than 100 years ago, still remains one of the main
      challenge facing rheumatologist and other physicians. The diagnosis of
      neuropsychiatric SLE (NPSLE) is complex not only because of the considerable
      prevalence variation (14-80%) but also because of the wide spectrum of NP
      manifestations. They vary from overt neurologic alterations (seizure, psychosis),
      to subtle abnormalities (neurocognitive dysfunctions). Different NP
      manifestations result from a variety of mechanisms including antibodies,
      vasculitis, thrombosis, hemorrhages and cytokine-mediated damages. Of note,
      despite the dramatic clinical manifestations, too often changes at the
      morphological neuroimaging techniques are minimal and non specific. There is no
      one diagnostic tool specific for NPSLE and diagnosis must be based on the
      combinated use of immunoserological tests, functional and anatomical neuroimaging
      and standardized specific criteria. Symptomatic, immunosuppressive and
      anticoagulant therapies are the main strategies available in the management of
      these patients. Therapy for CNS lupus should be adjusted according to the needs
      of the individual patients. The coming years promise to be an important time for
      the development of new neuroimaging techniques and for the study of disease
      mechanism. An early and objective identification of brain involvement will allow
      for appropriate treatment to avoid severe complications.

PMID- 17013434
TI  - [Thalidomide in treatment of connective diseases and vasculities].
AB  - Thalidomide is an immunomodulatory, anti-inflammatory and anti-angiogenic drug.
      Thalidomide exerts its effects by decreasing circulating CD4 positive T-cells and
      stimulating CD8 positive T-cells, by increasing the number of Natural Killer
      cells and T-helper 2 cells. Thalidomide also inhibits proliferation of stimulated
      T-cells and leukocyte chemotaxis. It modifies a number of integrin receptors and
      other leukocytic surface receptors and down-modulates cell-adhesion molecules
      involved in leukocyte migration. It has been demonstrated that thalidomide
      inhibits TNFalpha, IL-5, IL-6, IL-8, IL-12 production and increases production of
      IL-2, IL-10 and INFgamma. Moreover thalidomide plays an important role in
      inhibition of VEGF and FGF-2 mediated angiogenesis. Although the exact mechanism
      of action is not fully understood and only limited treatment opinions exist,
      thalidomide plays a role also in connective diseases and vasculities. Thalidomide
      has been seen efficacious in the treatment of cutaneous disorders in patients
      with systemic lupus erythematosus and in mucocutaneous disease in Behcet's
      disease with a not dose-dependent response, even if it should be restricted to
      selected patients because of its important side effects.

PMID- 17013435
TI  - [Occupational therapy in rheumatoid arthritis: short term prospective study in
      patients treated with anti-TNF-alpha drugs].
AB  - OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid
      arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open
      controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56
      (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated
      with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group.
      We evaluated at entry and 12 weeks the following outcome parameters including
      Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global
      Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and
      physician disease activity, Disease Activity Score (DAS28), erythrocyte
      sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to
      items regarding activity daily living (ADL). RESULTS: At baseline, OT and control
      group had similar demographic and clinical features. After 12 weeks, the changes
      from baseline of main outcome parameters were not significantly different between
      the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the
      percentage of patients showing a correct adherence was significantly increased in
      OT group only. Moreover at the end of the study, the OT group showed a correct
      adherence to 8 out of 11 ADL items in an higher percentage of patients respect to
      the control group. CONCLUSION: Our study sustains that OT improves self
      management but not main parameters of disease activity or functional capacity.
      Nevertheless educational intervention should be considered as a useful tool in
      conjunction with pharmacological treatment.

PMID- 17013436
TI  - [Are there any positive effects of TNF-alpha blockers on bone metabolism?].
AB  - Secondary osteoporosis (OP) is a well-recognized complication of rheumatoid
      arthritis (RA). Treatment with TNF-alpha blockers, might influence bone
      metabolism and prevent structural bone damage in RA, in particular at the
      periarticular regions. OBJECTIVE: To assess the influence of anti-TNF-alpha
      therapy, on bone metabolism in RA patients. 36 RA patients were treated with
      stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX=10 mg/week). Nine
      of these RA patients further received etanercept (25 mg, twice/weekly) and eleven
      infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group
      included 16 RA patients only with stable therapy (some dosage of prednisone and
      MTX). Quantitative Ultrasound (QUS) bone densitometry was obtained at the
      metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS
      device (IGEA, Carpi, Italy). Bone mineral density (BMD) of the hip and lumbar
      spine were performed with a densitometer ( Lunar Prodigy, GE, USA) at baseline
      and after 12 months. Soluble bone turnover markers [osteocalcin (OC), bone
      alkaline phospatase (ALP) deoxypyridinoline/creatinine ratio (Dpd/Cr) and cross
      linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr)] were
      measured using ELISA tests. RESULTS: AD-SoS values were found increased by +4.55%
      after 12 months of treatment in the RA patients treated with anti-TNF-alpha
      therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same
      period in the control RA group. BMD increased by +3.64% at lumbar spine and
      +2.90% at the hip (both p<0.001) in TNF-alpha blockers-treated patients and
      decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at
      the hip) in RA patients without anti-TNF-alpha therapy. In RA patients treated
      with TNF-alpha blockers, OC and bone ALP levels were found significantly
      increased (p<0.01) and Dpd/Cr or NTx/Cr levels were found significantly decreased
      (p<0.01) at 12 months when compared to baseline values. CONCLUSION: During 12
      months of treatment of RA patients with TNF-alpha blockers, bone formation seems
      increased while bone resorption seems decreased. The reduced rate of OP seems
      supported by the same mechanisms involved in the decreased bone joint resorption
      during anti-TNF-alpha therapy (i.e. increase of osteoblastic activity and
      decrease osteoclastic activity).

PMID- 17013437
TI  - [Comparation of levels of anxiety and depression in patients with autoimmune and
      chronic-degenerative rheumatic: preliminary data].
AB  - Scientific research on rheumatic diseases was often focused on the link between
      psychological features and disease. Depression and anxiety are frequently
      observed with an higher incidence among rheumatic patients in comparison to
      general population. In autoimmune diseases, such as rheumatoid arthritis, an
      important role for psychiatric symptoms could be played by the alteration of
      cytokines levels. In the chronic-degenerative diseases, psychological factors
      such as stress and depression, can be involved in perception of pain. OBJECTIVE:
      We aimed at evaluating in a sample of 50 patients (25 with rheumatoid arthritis
      and 25 with osteoarthritis) levels of pain, anxiety and depression. METHODS: We
      evaluated two group of patients with rheumatic disease, group A (25 with
      Rheumatoid Arthritis, mean age = 45.1; DS =15.24) and group B (25 with
      osteoarthritis, mean age = 54.3; DS =14.74) by clinic examination and with the
      following tests, SF-MPQ, HAQ, HAM-A, HAM-D. RESULTS: We found in group A higher
      levels of depression and anxiety but lower levels of pain, which was more
      expressed in group B. CONCLUSION: Depression and anxiety were observed with an
      higher prevalence in patients with autoimmune disease, whereas pain was stronger
      in patients with osteoarthritis, a degenerative disease. We could explain this
      phenomenon considering the aetiopathology of the two conditions. As regard to
      autoimmune disorders, these symptoms may reflect the direct effect of cytokines
      on the central nervous system. As far as it concerns chronic-degenerative
      diseases, anxiety and depression are usually considered "reactive" to pain, not
      "constitutive".

PMID- 17013438
TI  - [Chronic inflammation and endothelial dysfunction: analysis of a cohort of
      patients with SLE and UCTD].
AB  - OBJECTIVE: Cardiovascular complications, mainly caused by an accelerated
      atherosclerosis, are one of the leading causes of death and disability in
      patients with systemic autoimmune diseases. Endothelial dysfunction is considered
      the earliest and reversible step of atherogenesis. Aim of the present study is to
      investigate endothelial function (EF) in patients with systemic lupus
      erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and
      correlate the results with clinical and laboratory variables. METHODS: EF was
      assessed on the peripheral microcirculation by the perfused forearm technique
      that can estimate both endothelium- dependent and endothelium- independent
      vasodilatation. The same evaluation has been repeated in two patients after the
      administration of 20 mg of 6-metilprednisolone. RESULTS: Twenty-three female
      patients with SLE or UCTD, with a follow up of at least 1 year have been studied
      and compared with 8 healthy controls matched for epidemiological variables and
      traditional risk factors for cardiovascular disease. A significant reduction both
      in endothelium dependent than endothelium independent vasodilatation was observed
      in both patients groups compared with controls. In addition, UCTD patients
      demonstrated a significant reduction in the nitric oxide pathway compared with
      controls and SLE patients. Finally, steroid administration induced an improvement
      of vascular reactivity. CONCLUSIONS: Despite the well documented side effects of
      chronic corticosteroid therapy, our data might suggest a role for antinflammatory
      and immunosuppressive therapy in the prevention of premature atherosclerosis in
      patients with systemic autoimmune diseases.

PMID- 17013440
TI  - [Quality of life and associated clinical distress in fibromyalgia].
AB  - OBJECTIVES: Fibromyalgia (FM) is a syndrome characterized by chronic, diffuse
      musculoskeletal pain and by a low pain threshold at specific anatomical points
      (tender points). Numerous other conditions (Irritable bowel syndrome, tension
      type headache, migraine headaches, etc.) may overlap with FM. Aim of this study
      was to evaluate the quality of life and associated clinical distress in patients
      with FM. METHODS: 53 females affected by primary fibromyalgia and 40 healthy
      females were examined were examined by an experienced rheumatologist and
      interviewed using the Fibromyalgia Impact Questionnaire (FIQ). Clinical
      monitoring included Visual Analogue Scale for pain and pain pressure threshold
      measurements. RESULTS: Mean FIQ scores were 66.39+/-14.94 in FM patients and
      13.15+/-5.37 in control subjects and the difference was statistically
      significant. Among associated clinical distress higher frequencies have been
      found for paraesthesia (87%), sleep disturbance (72%), tension type headache
      (70%), oto-vestibule syndrome (72%) and irritable colon (60%). An R.O.C. bend was
      developed in the presence of paraesthesias and oto-vestibule syndromes at the
      same time. This allowed us to identify a FIQ cut off value of 66.85 so FM
      patients were divided into 2 groups according to their FIQ scores: severe degree
      and mild or slight degree. CONCLUSIONS: Based on our data, it would appear
      possible to use a FIQ value equal to or higher than 66.85 for the clinical
      picture of FM to be classified as severe.

PMID- 17013439
TI  - [Determinants of depression in 111 Italian patients with systemic sclerosis].
AB  - BACKGROUND: A high prevalence of depressive symptoms has been described in
      systemic sclerosis (SSc), but no clear association with organ involvement or
      objective indices of disease severity has been depicted. To date, no effort has
      been made to determine the prevalence of depressive symptoms in Italian patients
      with SSc or to clarify their cause. METHODS: One-hundred-eleven SSc patients were
      asked to fill in the Beck Depression Inventory (BDI) questionnaire, the
      scleroderma Health Assessment Questionnaire (sHAQ) and two additional questions
      assessing the patient's familiar support and the social consequences of the
      patient's change in physical appearnace. RESULTS: Thirty-seven subjects (33.4%)
      presented mild to severe depressive symptoms (BDI >/=17). On univariate analysis
      the diffuse cutaneous form of the disease (p=0.019), higher pulmonary systolic
      pressures on echocardiogram (p=0.016), lower FVC percentage of predicted values
      (p=0.022), higher sHAQ values (p<0.001) or higher VAS values for pain (p=0.007),
      lung involvement (p=0.02), Raynaud's phenomenon severity (p=0.002), ulcers
      severity (p=0.006) or disease severity (p<0.001), were associated with the
      presence of pathologic depressive symptoms. On multivariate analysis only the VAS
      for disease severity relevant to BDI scores (p=0.016). Social behaviour changes
      due to SSc-related physical involvement were reported in 14 patients (38%) with
      depressive symptoms (p=0,006) and were more likely to be observed in younger
      patients (p=0.001) with a more severe Raynauds's phenomenon (p=0.013).
      CONCLUSIONS: Mild to severe depressive symptoms are common in SSc patients
      especially in those with a worse perception of disease severity, these patients
      should be carefully monitored and a psychological assistance counselled whenever
      necessary.

PMID- 17013441
TI  - [Dactilitis and oligoarthritis after BCG immunotherapy in a patient affected by
      bladder cancer].
AB  - The treatment of bladder cancer with Bacillus of Calmette-Guerin (BCG)
      immunotherapy can induce the appearance of a reactive disorder. The Authors
      describe a 55-year-old male patient with bladder cancer treated with endovesical
      instillation of BCG immunotherapy, followed after the fifth application by
      asymmetric oligoarthritis and dactilitis. The observed positivity of both HLA-B27
      and HLA-B51 antigens reinforces the hypothesis of a reactive form, possibly
      through "molecular mimicry" mechanism. The discontinuation of BCG instillation
      along which a therapeutic attempt with NSAD failed to improve the rheumatic
      manifestation, which completely remitted after a four-month course of oral
      steroids. No relapses of joint and tendon involvement was observed during the
      following five-month period. The clinico-pathogenetic implications suggested by
      this case are discussed.

PMID- 17013442
TI  - [Ultrasonographic assessment of the response to Etanercept treatment in patients
      with rheumatoid arthritis].
AB  - OBJECTIVES: To evaluate, using musculoskeletal ultrasound (MSUS), the effects of
      Etanercept therapy in patients with rheumatoid arthritis (RA) over 3 months of
      treatment. METHODS: Eighteen consecutive patients, 3 male and 15 female, affected
      by RA (ACR criteria) who were non-responders or partial responders to DMARDs
      therapy were commenced on Etanercept treatment. MSUS was performed bilaterally in
      the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist and knee joints,
      using a Philips/HP Image Point HX machine with a 7,5 MHz linear probe for knee
      joints and a 14 MHz probe for the hands and wrists. In addition, power Doppler
      was used with the following settings: PRF 700-1000Hz, gain 60-65 dB, low filter.
      For all the changes a semi-quantitative score (0-3) was used to indicate the
      presence of a localised inflammatory process (synovitis, tenosynovitis). An
      overall score was then calculated based on the sum of the single scores in order
      to obtain a comprehensive score indicative of the global pathological change.
      RESULTS: The overall score significantly (p<10-5) reduced between T0 (8,5) and T3
      (5). Even the most part of the local joint scores significantly reduced.
      CONCLUSIONS: A positive response to treatment with Etanercept was demonstrated by
      MSUS examination of several joints. The results of our study are supportive of
      those presented in other reports where MSUS was used to monitor disease activity.
      We were able however to demonstrate this in a wider range of anatomical targets
      than in previous studies. MSUS is a useful tool in the monitoring of biologic
      therapy in RA.

PMID- 17013443
TI  - [Dupuytren's disease].
AB  - Dupuytren's disease is a contracture of the hand derived from the retractile
      fibrosis of the palmar aponeurosis, that leads to a progressive deformity in
      flexion of fingers. It has been named from the French surgeon Guillaume Dupuytren
      (1777-1835), that described it in 1831. In this note it is sketched a short
      biography of Dupuytren and the main clinical features of the disease are
      described, underlining some particular aspects of therapy.

PMID- 17013444
TI  - Hepatitis C virus survival curve analysis in naive patients treated with
      peginterferon alpha-2b plus ribavirin. A randomized controlled trial for
      induction with high doses of peginterferon and predictability of sustained viral
      response from early virologic data.
AB  - AIM: To evaluate the significance of induction with high doses of pegylated
      interferon -2b (Peg-IFNalpha-2b) and the predictability of sustained virologic
      response (SVR) in naive patients with chronic hepatitis C. METHODS: 188
      consecutive naive patients with chronic hepatitis C were enrolled in a randomised
      controlled clinical trial. Patients were randomised to receive either Peg-IFN -2b
      3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800-1200 mg
      ribavirin (Arm A) or Peg-IFNalpha-2b 1.5 mcg/kg QW x 48 weeks plus 800-1200 mg
      ribavirin (Arm B). HCV-RNA was obtained at 0, 4, 8, 12, 16, 24, 48 and 72 weeks.
      Differences between schemes were evaluated by Kaplan-Meier curves. Predictability
      of SVR was assessed by two-way contingency table analysis and ROC curve analysis.
      RESULTS: From 176 patients, 75 had genotype 1, 15 genotype 2, 75 genotype 3 and
      11 genotype 4. No statistical significance emerged in HCV-RNA positivity, side
      effects and withdrawals between schemes. Patients with genotype 1 achieved lower
      SVR (46.6%) in comparison to patients with genotypes 2/3 (94.1%, p < 0.001) and 4
      (90.9%, p = 0.002). The most appropriate time for estimation of SVR for genotype
      1 is week 8 (accuracy = 0.84, AUC = 0.90) while predictability increases with
      time in genotypes 2/3, reaching maximum accuracy = 0.93 and AUC = 0.76 at week
      16. CONCLUSION: Induction with high doses of Peg-IFNalpha-2b does not preclude
      better outcome and rapid virologic response at 4 weeks of treatment sufficiently
      predicts SVR. These findings might be useful in an attempt to gain supportive
      evidence for decision making in difficult-to-treat patients.

PMID- 17013445
TI  - Positive coeliac serology in irritable bowel syndrome patients with normal
      duodenal biopsies: Video capsule endoscopy findings and HLA-DQ typing may affect
      clinical management.
AB  - OBJECTIVES: To investigate a group of IBS patients (Rome criteria) with positive
      coeliac serology (EMA, TTG, IgG or IgA AGA) and normal small bowel biopsies.
      Video capsule endoscopy (VCE) findings of the small bowell were compared with DQ
      typing. METHODS: Twenty-two patients with chronic abdominal pain (with or without
      diarrhea) and at least one positive result of any of the coeliac serological
      markers (AGA, TTG, EMA) and normal duodenal biopsy were enrolled and underwent
      VCE. Twelve healthy volunteers with VCE served as control group. Coeliac related
      HLA DQ2 or DQ8 markers were determined. RESULTS: 12/ 22 (55%) patients had small
      bowel abnormalities with VCE. No mucosal abnormalities were recognized in the
      control group (p = 0.002). Inflammatory changes were classified as moderate or
      pronounced. Eight patients (36%) had moderate changes and four patients (18%)
      demonstrated pronounced changes. Only 6 of the 21 IBS patients were positive for
      DQ2 and/or DQ8. CONCLUSIONS: The patients in this study fulfilled the diagnostic
      Rome criteria for Irritable Bowel Syndrome. We suggest that patients with
      positive coeliac serology and normal duodenal biopsies should undergo HLA typing.
      In patients positive for DQ2 and/or DQ8, a VCE should be performed. Patients with
      mucosal abnormalities compatible with CD should be considered as a group distinct
      from IBS patients and could be tested with gluten challenge or treated with a
      gluten free diet.

PMID- 17013446
TI  - What general practitioners know about irritable bowel syndrome. Preliminary data
      from a Romanian province.
AB  - BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common disorder in
      Romania, managed frequently by General Practitioners (GPs). It is necessary to
      assess the knowledge of GPs on IBS. A preliminary investigation was carried out
      in two Romanian counties. METHODS: One hundred GPs were invited to a two hour,
      free, updating course on IBS. The participants were asked to fill a questionnaire
      before and after the course which comprised questions about medical experience,
      demography, and several multiple-choice questions about GPs opinions and
      awareness. The final question assessed the estimated prevalence of IBS in the
      practice. RESULTS: Full responses to both questionnaires were obtained from all
      attending GPs (n=88). They were 25 males: 63 females, with working experience
      between 3 and 41 years (mean +/- SD: 24 +/- 11). Apart from 2 (2.4%) who
      indicated that IBS is a motility disorder (opinion revised after the course), all
      other GPs considered IBS as a functional disorder. All (100%) opted for the
      necessity of colonoscopy to diagnose IBS. 98.8% indicated the use of Rome II
      criteria for the diagnosis of IBS (this survey was done before the availability
      of Rome III but their advent was mentioned). All (100%) had participated in
      previous lectures or courses on IBS. 58 (66%) reported the prevalence of IBS in
      their practice between 1-10%; 16 (18%) between 10-25%; 11 (12.5%) between 25-33%;
      3 (3.5%) reported <1%. CONCLUSIONS: The investigated GPs seem to be well trained
      in recognizing IBS. The majority (66%) estimated the prevalence of this condition
      as 1-10% in their practice.

PMID- 17013447
TI  - Infliximab reduces the number of activated mucosal lymphocytes in patients with
      Crohn's disease.
AB  - BACKGROUND: Infliximab is an effective treatment for Crohn's disease in patients
      with poor prior response to conventional therapy. The mechanism by which
      infliximab induces clinical improvement is not completely known. AIM: The aim of
      the study was to investigate the influence of infliximab on immunological
      parameters in peripheral blood and inflamed intestinal mucosa. METHODS: Twenty
      five patients with Crohn's disease (11 with luminal and 14 with fistular form)
      underwent treatment with infliximab. The lymphocyte populations from the
      peripheral blood and the inflamed intestinal mucosa were analysed by flow
      cytometry before treatment and 14 days later. RESULTS: After treatment, the
      peripheral blood analysis showed a significant increase in the percentage of CD19
      cells and the concentrations of CD3, CD4, CD8 and activated (HLA DR positive) T
      cells, while the percentage of NK cells was reduced. In the inflamed mucosa, a
      significant decrease in the percentage of activated T cells and expression of HLA
      I molecules by epithelial cells was noted. CONCLUSIONS: Infliximab profoundly
      downregulates inflammation in the intestinal mucosa of patients with Crohn's
      disease. This effect is manifested by a reduction of activated T cells, main
      producers of proinflammatory cytokines, in the inflamed mucosa.

PMID- 17013448
TI  - Rome III: New standard for functional gastrointestinal disorders.
AB  - The publication in the April, 2006 issue of Gastroenterology of Rome III has made
      available to the scientific world an enhanced and updated version of the Rome
      criteria and related information on the functional GI disorders. It is expected
      that the criteria will be adopted and used by physicians, pharmaceuticals and
      regulatory agencies worldwide, just as the previous Rome II became the standard
      for clinical practice and research. In this issue of J Gastrointestin Liver Dis,
      these Guidelines, the Rome III, are presented. Also included are some of the
      differences between Rome II and Rome III criteria as well as the rationale for
      publishing this new version.

PMID- 17013449
TI  - Update in the diagnosis of gastroesophageal reflux disease.
AB  - Clinical manifestations of gastroesophageal reflux disease (GERD) include
      heartburn, regurgitation, dysphagia, chest pain, cough and other extraesophageal
      symptoms. GERD is known to cause erosive esophagitis, Barrett esophagus and has
      been linked to the development of adenocarcinoma of the esophagus. Currently
      upper gastrointestinal endoscopy is the main clinical tool for visualizing
      esophageal lesions. Since the majority of GERD patients do not have endoscopic
      visible lesions other methods are required to document the abnormal acid exposure
      in the distal esophagus. For many clinicians ambulatory esophageal pH monitoring
      is the gold standard in diagnosing GERD since it quantifies distal esophageal
      acid exposure and allows the evaluation of the relationship between symptoms and
      acid reflux. The availability of highly selective gastric acid suppressive
      therapy led to the introduction of short trials of proton pump inhibitors (PPI)
      to diagnose GERD. PPI trials are often used as a first line diagnostic tool in
      clinical practice and in particular in the primary care settings. This
      development has a major influence in the type of patients referred to
      gastrointestinal specialists, the current trend being that gastroenterologists
      are asked to evaluate an increasing number of patients with persistent GERD
      symptoms while on PPI therapy. In these patients the question is whether the
      persistent symptoms are or not associated with reflux (acid or non-acid). In the
      recent years combined multichannel intraluminal impedance and pH (MII-pH)
      monitoring has become a clinical tool that permits the clarification of the
      mechanisms underlying the persistent symptoms on acid suppressive therapy.

PMID- 17013450
TI  - Acute hepatitis C virus infection: Diagnosis, pathogenesis, treatment.
AB  - Diagnosing acute hepatitis C is still difficult. The disease is frequently
      asymptomatic and there are no specific diagnostic tests. Most frequently,
      diagnosis is based on anti HCV antibodies serum conversion and, more rarely, on a
      double serum conversion (initially HCV-RNA undetectable by RT-PCR, subsequently
      positive and serum conversion for HCV antibodies determined by EIA and RIBA
      techniques). Evolution of HCV infection is determined by the intensity of immune
      response, type of secreted cytokines and persistence of specific HCV T
      lymphocytes response. Patients achieving viral clearance present an early, strong
      and multi specific T lymphocyte response. Spontaneous viral clearance rates are
      highly variable between 10-60%. It is currently recommended to delay start of
      treatment for 2-4 months after onset and this delay does not compromise chances
      of achieving sustained virologic response. It is necessary to repeat viremia 6
      months -1 year after spontaneous viral clearance due to the possibility of viral
      replication restart. There are currently no firm guidelines regarding treatment
      regimens, treatment duration and timing of its initiation. Monotherapy with high
      dose interferon alpha or peg-interferon for 6 months is recommended. Although
      important progress has been achieved in acute hepatitis C understanding, research
      continues to improve treatment regimens and to clarify mechanisms of viral
      clearance.

PMID- 17013451
TI  - Diagnostic and therapeutic approach to pancreatic adenocarcinoma.
AB  - Pancreatic adenocarcinoma is the sixth leading cause of cancer-related death in
      Europe with survival rates remaining unchanged over the last three decades. Early
      diagnosis and accurate staging are essential due to the difficulty of curing this
      tumor in its advanced form. Endoscopic or laparoscopic ultrasonography and
      computed tomography are the preferred imaging and staging modalities for many
      patients with pancreatic adenocarcinoma. Morbidity and mortality are similar for
      pylorus-preserving and classic pancreatico-duodenectomy. Extended retroperitoneal
      lymphadenectomy does not improve survival and increases morbidity compared with
      standard pancreaticoduodenectomy, while adjuvant chemoradiotherapy prolongs
      survival in selected groups of patients. This article reviews the causes, risk
      factors, and clinical features of pancreatic adeno-carcinoma and discusses the
      methods of optimal diagnosis, staging and treatment.

PMID- 17013452
TI  - The role of imaging methods in identifying the causes of extrahepatic
      cholestasis.
AB  - Transabdominal ultrasonography is the first choice examination used for the
      etiological diagnosis of extrahepatic cholestasis because it is a noninvasive,
      rapid method and presently widely accessible. In this article we discuss the
      accuracy of transabdominal ultrasonography, computed tomography (CT), endoscopic
      retrograde cholangiopancreatography (ERCP), magnetic resonance
      cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) in detecting
      the main causes of extrahepatic colestasis. Although in bile duct pathology, and
      especially in the evaluation of patients with jaundice, transabdominal
      ultrasonography is the first choice exploration, helicoidal CT, ERCP and MRCP are
      often required to establish the local cause of jaundice, local and distant
      consequences evaluation, appreciation of surgical intervention opportunity and
      choice of the right therapeutic method.

PMID- 17013453
TI  - Hepatic perfusion disorders: Computer-tomographic and magnetic resonance imaging.
AB  - The liver has a unique dual blood supply from the hepatic artery (25%) and the
      portal vein (75%). Helical computer tomography (CT) and also magnetic resonance
      imaging (MRI) are suitable techniques for hepatic imaging. Helical CT and MR
      angiography allow single breath-hold scanning without motion artifacts. This
      article illustrates helical CT and MRI findings of different types of hepatic
      perfusion disorders. Because of rapid image acquisition, three-phase (hepatic
      arterial phase, portal venous phase and parenchymal phase) CT or MR-angiography
      evaluation of the hepatic parenchyma is possible, improving perfusion disorders
      evaluation, tumors detection and characterization in a single study. We
      classified hepatic perfusion abnormalities in: portal disorders, arterial
      disorders, hepatic veins abnormalities, intrahepatic vascular communication,
      hepatic lesions and perfusion disorders and other causes. Differential diagnosis
      and pitfalls of these entities must be known for a correct diagnosis of focal
      hepatic lesions.

PMID- 17013454
TI  - Endoscopic ultrasound-guided fine needle aspiration used for the diagnosis of a
      retroperitoneal abscess. A case report.
AB  - BACKGROUND: The evaluation of idiopathic abdominal masses by EUS-guided fine
      needle aspiration (FNA) is considered a feasible and safe option. Moreover,
      different case reports and small case series recently described EUS-guided
      drainage of abscesses located nearby the digestive tract as a viable option of
      mini-invasive treatment. CASE REPORT: We present the case of a young patient with
      a retroperitoneal abscess diagnosed by EUS-guided FNA. Trans-abdominal ultrasound
      (TUS) and computer tomography (CT) scan were helpful, but insufficient for the
      final diagnosis. Although the abdominal mass was clearly visualized by these
      imaging methods, it was not possible to differentiate between a cystic tumor mass
      and an abscess. The mass was located in the vicinity of the pancreas tail, near
      the spleen and superior pole of the left kidney. The case management was complex
      due to the associated disorders and occurrence of severe episodes of hemolytic
      anemia. The association of gastric varices and left-sided portal hypertension
      further complicated the differential diagnosis and precluded percutaneous
      aspiration procedures. EUS-guided FNA established the final diagnosis, because of
      pus aspiration and positive bacterial cultures that sustained the initial
      supposition. The patient was referred to surgery and the evolution was favorable
      after abscess drainage and splenectomy. CONCLUSION: EUS-FNA is an excellent
      option used to obtain a tissue diagnosis in suspicious retroperitoneal masses,
      with a clear impact for the management decisions of these patients.

PMID- 17013455
TI  - Spontaneous splenorenal shunt in a patient with liver cirrhosis and hypertrophic
      caudal lobe.
AB  - Spontaneous splenorenal shunt is a rare condition, sometimes causing
      complications in cirrhotic patients. We report a 30-year old man with liver
      cirrhosis, hypertrophic caudal lobe and spontaneous splenorenal shunt. Real-time
      and color Doppler ultrasonography evidenced enlarged caudal lobe (130 x 95 mm)
      with direct veins draining into dilated inferior cava vein (diameter 25 mm, flow
      52 cm/sec). In the left renal hilus a large vein with a flow typical for portal
      vein system was found, velocity 25-37 cm/sec. Indirect splenoportography noticed
      splenomegaly, dilated lienal and portal vein with hepatopetal blood flow,
      perisplenic varices, and large spontaneous splenorenal shunt. Whole inferior
      caval vein was dilated, while hepatic veins were intact. Hemodynamic consequences
      of this large shunt were dilation of inferior cava vein with hyperkinetic
      systemic flow, and secondary hypertrophy of liver caudal lobe.

PMID- 17013456
TI  - Inferior mesentericocaval shunt--an efficient therapeutical alternative in Budd
      Chiari syndrome associated with portal and splenic vein thrombosis in a teenager.
AB  - The authors present the case of a 17 year old girl admitted to hospital for poor
      general state, mild scleral jaundice, deficient nutritional state, oliguria and
      massive ascites. She was diagnosed with Budd-Chiari syndrome: thrombosis of the
      left suprahepatic vein and nonocclusive thrombosis of the inferior vena cava at
      the level of the 12th thoracal and the lumbar vertebrae. The specific feature of
      the case was the association of portal and splenic vein thrombosis. A
      mesentericocaval shunt with external jugular grefon was performed. The evolution
      at 20 months after surgery has been favorable. She has no ascites, the
      nutritional state has normalized and hepatic laboratory findings have returned to
      normal values. There still persists a high consistency splenomegaly, but without
      hematological hypersplenism. Even though the mesentericocaval shunt is not
      without complications, it represents an efficient alternative for the treatment
      of Budd-Chiari syndrome, when endovascular techniques are not available.

PMID- 17013457
TI  - Perforated GIST of the small intestine as a rare cause of acute abdomen: Surgical
      treatment and adjuvant therapy. Case report.
AB  - A case of perforated gastrointestinal stromal tumor (GIST) of small intestine
      causing acute abdomen is described, with a brief review of the literature. A male
      patient presented with symptoms of acute abdomen. After evaluation, a laparotomy
      was performed, where perforation of a tumor in the ileum was found. The
      perforated part along with the tumor was resected and the cytopathological
      examination showed that the tumor was GIST. Postoperatively, the patient received
      treatment, using imatinib. Gastrointestinal stromal tumors are relatively rare
      and often present with vague symptoms. Their first clinical manifestation as
      acute abdomen due to their perforation is extremely rare. In emergency
      laparotomy, a R0 resection is required and adjuvant therapy with imatinib must be
      considered.

PMID- 17013458
TI  - Multiple peritoneal hydatid disease after rupture of a multivesicular hepatic
      hydatid cyst. Case report.
AB  - We report the peculiar case of a young woman with hepatic hydatid cysts, with
      numerous peritoneal disseminations (56 cysts) incidentally diagnosed during a
      caesarian section. The case was managed, surgically preceded and followed by
      systemic treatment with albendazole. Surgical treatment addressed both the
      hepatic cyst and the peritoneal hydatid disease aiming to preserve involved
      abdominal organs. The diagnosis of peritoneal hydatid disease is today more
      accurate due to the new imaging techniques and the surgical procedure should be
      tailored to each patient depending on size, location and complications of each
      cyst. Radical treatment is the best and represents a goal, but with multiple
      disease, a staged treatment and special care for organ preservation should
      prevail as recurrences are not unusual.

PMID- 17013459
TI  - The survey on the practice of gastroenterology in Romania.
AB  - AIM OF THE STUDY: To get data on the current practice of Gastroenterology in
      Romania. MATERIAL AND METHOD: We obtained data regarding the number of
      gastroenterologists in Romania from the Centre of Statistics of the Ministry of
      Health and Family (CSMHF) and the National Centre of Training for Medical
      Personnel (NCTMP). We sent a questionnaire to all the Centers of Gastroenterology
      in Romania inquiring about the number of gastroenterologists and fellows, and
      about the gastroenterological procedures performed. We compared these data to
      that of 17 European countries. RESULTS: The total number of gastroenterologists
      in Romania on January 1, 2005 was 175 (123 specialists and 52 senior
      consultants), and the total number of fellows in training was 133. Romania has a
      small number of gastroenterologists - 0.83/100,000 inhabitants, expected to reach
      approximately 1.4/100,000 inhabitants in 2010. Regarding the abilities in
      gastroenterological procedures, we obtained data from 98 gastroenterologists.
      They have good performances in diagnostic gastroscopy (97%), colonoscopy (81.6%),
      abdominal ultrasound (79.6%), but a poor performance in ERCP (10.2%). Less than
      half of the gastroenterologists (46.9%) perform proctologic procedures. Data
      regarding the training program of the Romanian fellows are disappointing: only
      69.1% of them perform gastroscopy, 33.8% colonoscopy, 2.9% ERCP, 64.7% abdominal
      ultrasound and 14.7% proctology. CONCLUSIONS: The number of gastroenterologists
      in Romania seems low compared with most European countries. They do not acquire a
      uniform satisfactory mastering of gastroenterological procedures during their
      training program. This should be improved according to the guidelines of the
      European Diploma of Gastroenterology.

PMID- 17013460
TI  - Peptide nucleic acids for the detection of YMDD in chronic hepatitis B.

PMID- 17013461
TI  - An unusual cause of overt gastrointestinal bleeding.

PMID- 17013462
TI  - Endoscopic rubber band ligation for bleeding oesophageal varices in portal
      hypertension due to idiopathic myelofibrosis.

PMID- 17013463
TI  - Brain natriuretic peptide in heart failure and beyond.
AB  - Hospital admissions with heart failure (HF) are increasing worldwide. It is the
      main reason for hospitalization of elderly patients. Heart failure affects nearly
      15% of patients aged >75 years. Prognosis after diagnosis of HF is comparable to
      that of cancers with 50% survival after 4 years of mild HF and 50% after one year
      in more severe cases. Current data increasingly suggest that measurement of brain
      natriuretic peptide (BNP) is very useful in diagnosis, treatment, prognosis and
      risk stratification of patients with HF and beyond. This paper reviews the
      available literature concerning the BNP and N-terminal pro brain-type natriuretic
      peptide to assess their role in current medical practice.

PMID- 17013464
TI  - A review of urinary stone analysis techniques.
AB  - Knowledge of the chemical composition and structure of urinary stones is of great
      value in the choice of treatment and prevention of recurrence. This is a brief
      review and a comparative study of the principles and practical application of
      various chemical and physical techniques used for urinary stone analysis. The
      different methods of classifying and grouping urinary stones by results of
      chemical analytic techniques are, also, compared and evaluated. In addition to
      reviewing various techniques used for the in-vitro analysis of removed stone
      samples, the newly emerging physical and radiological techniques for the in-vivo
      intact-stone analysis are, also, evaluated. These in-vivo techniques,
      particularly the rapidly advancing unenhanced spiral CT scanning, represent an
      important step forward towards the notion of non- destructive analysis of urinary
      stones while still in situ before the choice of treatment modality.

PMID- 17013465
TI  - Effects of coronary collateral vessels in left ventricular segmental motions and
      myocardial viability using color kinesis dobutamine stress echocardiography.
AB  - OBJECTIVE: To detect the functional importance of coronary collaterals, which
      develop after acute myocardial infarctions (AMI). METHODS: Forty patients with
      acute AMI whose coronary angiography demonstrated a total occlusion of the left
      anterior descendant (LAD) artery were included in the study, between January 2003
      and June 2004. All of the study patients underwent coronary angiography and left
      ventriculography using standard Judkins techniques (Phillips Integris-3000). Left
      ventricular (LV) free walls were divided into 5 segments, and all of these
      segments motions were evaluated then LV free wall motion score index (WMSI) was
      calculated. The study patients were divided into 2 groups: good (Rentrop 3; group
      I; n = 14) and poor coronary collateral circulation (Rentrop 0-2; group II; n =
      26) according to the Rentrop grading. Then, color kinesis dobutamine stress
      echocardiography (CK-DSE) was performed to all patients with standard techniques
      6 weeks after AMI. RESULTS: There were no significant differences for age,
      gender, risk factors for the coronary artery disease and use of the fibrinolytic
      therapy between the groups. There were no significant statistical differences for
      angiographic WMSI, left ventricular ejection fraction (LVEF), end-diastolic
      volume, end-systolic volume and end-diastolic pressures between the 2 groups. No
      difference was detected between Group I and II for initial EF, WMSI and peak dose
      WMSI in CK-DSE procedure. Viability was determined in all of the 14 patients in
      group I (100%) and 12 of 26 patients in group II (46%) (p = 0.03). CONCLUSION: In
      early periods of an AMI genesis of the coronary collateral circulation does not
      affect left ventricular global and regional systolic functions, but increase
      viability quite significantly. According to our findings early revascularization
      could be carried out in patients with good coronary collateral circulation
      without doing any test for viability.

PMID- 17013466
TI  - Wound healing activities of Bark Extract of Jatropha curcas Linn in albino rats.
AB  - OBJECTIVE: To investigate the wound-healing properties of crude bark extract of
      Jatropha curcas Linn in Wistar albino rats. METHODS: This work was carried out in
      the Department of Biochemistry, Kasturba Medical College, Manipal Academy of
      Higher Education, Manipal, Karnataka, India, in the year 2005. We divided the
      animals into 3 groups of 12 each. Group I was saline control without wound, group
      II was animals treated with JC extract in the dose of 2 ml/kg body weight with
      wound and group III was animals treated with 4 ml/kg body weight with wound. The
      wound healing parameters like wound breaking strength, epithelization period,
      percent wound contraction, granulation tissue breaking strength, granulation
      tissue dry weight, hydroxyproline level and histological features were assessed
      by using incision, excision and dead space wound models. RESULTS: The results
      obtained indicated that Jatropha curcas accelerates the healing process by
      increasing the skin breaking strength, granulation tissue breaking strength,
      wound contraction, dry granulation tissue weight and hydroxyproline levels. A
      significant decrease in epithelization period was also observed. The
      histopathological examination of granulation tissue showed much advanced phase of
      healing, with more collagen, which has organized to form bundles. CONCLUSION: The
      results of the study suggest that the crude bark extract of Jatropha curcas was
      very effective in accelerating wound healing process.

PMID- 17013467
TI  - Protective effect of melatonin against chlorpromazine-induced liver disease in
      rats.
AB  - OBJECTIVE: To evaluate the possible protective effect of orally administered
      melatonin against Chlorpromazine (CPZ)-induced liver disease in rats. METHODS: We
      performed this study in the College of Pharmacy, University of Baghdad during the
      period from May to October 2004. The hepatoprotective effect of melatonin was
      studied through treatment of rats with single dose (10 mg Kg(-1)) orally, 7 days
      before and during the period of CPZ treatment, and 7 days after the induction of
      suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde
      (MDA) and glutathione (GSH) in liver tissue homogenate, activities of the liver
      aminotransferases, alanine transaminase (ALT) and aspartate transaminase (AST) in
      serum, in addition to serum level of bilirubin (total and conjugated) were
      evaluated. Liver tissue sections were examined to follow histological changes.
      RESULTS: Analysis of data showed that treatment with melatonin significantly
      attenuated the oxidative stress parameters as evidenced by lowering MDA levels in
      tissue homogenate while not affecting GSH levels. Serum activities of ALT, AST
      and serum bilirubin were normalized with both pre-treatment and post-treatment
      with melatonin. Data revealed that post-treatments with both saline and melatonin
      restore hepatic activity; however, melatonin showed significant reduction in ALT
      activity and bilirubin level than saline post-treatment. Additionally,
      histological evaluation revealed improvement of liver damage in this respect.
      CONCLUSION: The presented data indicated that orally administered melatonin in
      pharmacological doses protects against CPZ-induced liver disease in rats.

PMID- 17013468
TI  - Effects of melatonin and zinc on glycemic control in type 2 diabetic patients
      poorly controlled with metformin.
AB  - OBJECTIVE: This project was designed to evaluate the effects of melatonin and
      zinc on the glycemic control in type 2 diabetes mellitus (T2DM) patients with
      inadequate response to the oral hypoglycemic agent metformin. METHODS: A placebo
      controlled, double-blind clinical trial was performed at the Specialized Center
      for Endocrinology and Diabetes, Al-Rusafa Directorate of Health, Baghdad, Iraq
      during the period from February to July 2005, in which 46 type 2 diabetic
      patients were selected and allocated into 3 groups, these groups were treated
      with single daily oral doses of both 10 mg melatonin and 50 mg zinc acetate
      alone; 10 mg melatonin and 50 mg zinc acetate in addition to the regularly used
      metformin or placebo, given at bed time for 90 days. We measured the fasting
      plasma glucose (FPG), glycated hemoglobin (HbA1C) and serum C-peptide before
      starting the treatment (zero time) and after 30 and 90 days of treatment. We also
      performed post-prandial glucose excursion test (PPGE) for selected patients from
      the second and third groups before starting the treatment and after 90 days.
      RESULTS: Daily administration of melatonin and zinc improved the impaired fasting
      and post-prandial glycemic control and decreased the level of glycated
      hemoglobin; addition of this treatment regimen in combination with metformin
      improved the tissue responses to this oral hypoglycemic agent. CONCLUSION: The
      combination of melatonin and zinc acetate, when used alone or in combination with
      metformin improves fasting and post-prandial glycemic control in T2DM patients.

PMID- 17013469
TI  - Causes and outcome of medication errors in hospitalized patients.
AB  - OBJECTIVE: To develop better understanding of Medication Errors (MEs) in the
      health care sector, and to improve the error prevention services in the hospital.
      METHODS: We conducted a retrospective study at the Hera General Hospital, Makkah,
      Saudi Arabia. The medical records were reviewed for adult hospitalized patients
      from June 1, 2000 to June 30, 2002. Patients demographic data, types, and causes
      of MEs, were recorded. The contributing factors, frequency and patient's outcome
      were also analyzed. RESULTS: A total of 2627 patient files were analyzed, 3963
      errors were studied as follows: 1559 files contain one error, 800 files with 2
      errors, and 268 with >3 errors. The most common type of error found was wrong
      strength (concentration) in 914 patients (34.79%), 807 patients (30.7%) had wrong
      route of administration, and 788 (30%) had wrong dosage form. On the other hand,
      the most common cause identified for MEs, was human factor, which accounted in
      1223 patients (46.49%). Miscommunication was the most common second cause in 920
      patients (35.02%), and the third common cause was name confusion [484, (18.43%)].
      Medication Errors were classified from a regulatory prospective into actual in
      735 patient files (28%), potential in 1866 (71%) and serious in 26 (0.98%).
      CONCLUSION: The study showed that wrong strength was the most common ME found and
      human factors were the most common cause contributing MEs. Therefore, focusing on
      these factors will definitely minimize MEs in hospitalized patients.

PMID- 17013470
TI  - Histological and laboratory features of patients undergoing liver biopsy at a
      university hospital in Central Saudi Arabia.
AB  - OBJECTIVE: To identify the most common liver pathologies seen in our center, to
      find the prevalence of advanced fibrosis and cirrhosis in patients with chronic
      hepatitis B and C, and to correlate the histological and laboratory features of
      the most common diseases and compare between them. METHODS: Liver biopsy
      procedures performed in our Gastroenterology Unit at King Khalid University
      Hospital, Riyadh, Kingdom of Saudi Arabia were traced from records between the
      years 1997-2003. Clinical, histopathological, and laboratory features were
      recorded. RESULTS: We identified 574 liver biopsies during the study period. Of
      the 502 included patients, males were 58.6%. The mean age of the patients was
      43.5 years. Approximately half of the biopsies (49%) were performed for patients
      with hepatitis C, followed by hepatitis B, for which 17% of the biopsies were
      performed. Patients with hepatitis B were approximately 10 years younger than
      patients with hepatitis C (p = 0.01). They were 10% more likely to be males. In
      terms of fibrosis, only approximately 17% of patients with hepatitis B and 27% of
      patients with hepatitis C had advanced fibrosis. CONCLUSION: Most liver biopsies
      performed in our center are performed for patients with hepatitis C. Rates of
      advanced fibrosis in our series are significantly lower than what was previously
      reported in other studies.

PMID- 17013471
TI  - Cervical cancer screening with pattern of pap smear. Review of multicenter
      studies.
AB  - OBJECTIVE: To estimate the frequency of abnormal cervical smears and to compare
      the findings with earlier reported data from Saudi Arabia. METHODS: The study was
      divided into 2 parts. The prospective part was conducted at King Abdul-Aziz
      University Hospital and a private laboratory by using the Bethesda System
      criteria and diagnostic entities in evaluating all the pap smears that were
      received during the period of January 2000 to December 2004. All reliable
      published literature on pap smear performed at different hospitals from 1990
      2004, from the Western and Abha regions of Saudi Arabia were retrospectively
      evaluated. RESULTS: A total of 5132 cases were evaluated in the prospective part
      of the study. The percentage of abnormal pap smears was 4.7%. The significant
      categories were atypical squamous cell of undetermined significance (2.4%), low
      grade squamous intraepithelial lesion (0.6%), high grade squamous intraepithelial
      lesion (0.4%) and atypical glandular cells of undetermined significance (1.1%).
      The malignant categories were squamous cell carcinoma (0.08%), adenocarcinoma of
      cervix in situ (0.02%) and invasive (0.04%). Other malignancies were 0.04% and
      neuroendocrine carcinoma was 0.02%. In the second part of the study, the total
      number of cases reported in the literature were 45596. The percentage of abnormal
      pap smear was 1.4 %. The total cases evaluated in the current study and the
      previous published studies were 50,728 and the frequency of abnormal pap smear
      was 1.6%. CONCLUSION: The percentage of abnormal pap smear was higher in the
      prospective part of this study than the previously reported results. Unified
      national programs for diagnosing cervical precancerous lesions should be
      established covering different region of the Kingdom to evaluate the magnitude of
      the problem.

PMID- 17013472
TI  - Etiologic agents of cervicovaginitis in Turkish women.
AB  - OBJECTIVE: To investigate the distribution of microbiologic agents causing
      cervicovaginitis. METHODS: We conducted the study between October 2002 and
      December 2004 in Abant Izzet Baysal University, Duzce School of Medicine
      Hospital, Turkey. The samples were obtained from the posterior vaginal fornix and
      cervix by swabs in 828 patients. Direct microscopic examination, culture and
      enzyme immune assay (EIA) methods were performed in all patients for diagnosis of
      microbiologic agents. RESULTS: Gardnerella vaginalis (G. vaginalis) were
      diagnosed in 254 (30.7%) patients, Candida albicans (C. albicans) in 152 (18.4%),
      Candida glabrata (C. glabrata) in 36 (4.3%), Candida species in 52 (6.3%),
      Staphylococcus aureus (S. aureus) in 62 (7.5%), Streptococcus group B in 28
      (3.4%), Escherichia coli (E. coli) in 42 (5.1%), Klebsiella species in 24 (2.9%),
      and Streptococcus group D in 8 (1%) patients in culture. Less frequent
      enterobacteria in 30 (3.6%) were: Pseudomonas species, Proteus species
      Enterobacter species, Hafnia alvei and Nonfermenter species. Neisseria gonorrheae
      (N. gonorrheae) was detected in one patient (0.1%) in culture. The Chlamydia
      trachomatis (C. trachomatis) antigen was detected by EIA methods in 130 (15.7%)
      patients and Trichomonas vaginalis (T. vaginalis) was observed in 8 (1%) patients
      by direct microscopic examination. CONCLUSION: Performing the etiologic diagnosis
      of cervicovaginitis is necessary in order to take appropriate therapeutic and
      preventive measures. Therefore, we recommend G. vaginalis, C. albicans and C.
      trachomatis should be investigated in patients having a diagnosis of
      cervicovaginitis in our population, since these were detected in a considerable
      number of cases. Additionally, C. glabrata and T. vaginalis should be kept in
      mind as possible pathogens.

PMID- 17013473
TI  - Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis
      factor-alpha in neonatal sepsis and meningitis.
AB  - OBJECTIVE: To investigate whether serum levels of interleukin-1alpha (IL-1alpha),
      IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are
      useful in the diagnosis of neonatal sepsis and meningitis and differentiate them.
      METHODS: Blood samples were collected from 35 full term neonates with suspected
      infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul
      Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003.
      On the basis of laboratory and bacteriological results, newborns were classified
      into: sepsis (n = 28), meningitis (n = 7), and healthy controls (n = 16). Sepsis
      groups were further subdivided according to culture results into: group 1 =
      proven sepsis (n = 6), group 2 = clinical sepsis (n = 14), and group 3 = possible
      infected (n = 8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using
      Enzyme-Linked Immunosorbent Assay while CRP by nephelometer. RESULTS: In sepsis
      and meningitis patients, serum levels of CRP (p < 0.01, p < 0.05,) and IL-1alpha
      (p < 0.001, p < 0.05) were elevated than controls. C-reactive protein levels
      elevated in proven sepsis (p < 0.001) and IL-1alpha elevated in all subgroups of
      sepsis (groups 1, 2, 3) compared with (p < 0.05, p < 0.001, p < 0.01) controls.
      Interleukin-6, TNF-alpha showed no significant differences between studied
      groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%),
      and negative predictive values (89% and 93%). CONCLUSION: Interleukin-1alpha and
      CRP increased in neonatal sepsis and meningitis, but cannot differentiate between
      them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal
      infection and its assessment may improve accuracy of diagnosis.

PMID- 17013474
TI  - Prevalence of anti-hepatitis B and anti-hepatitis A antibodies among school aged
      children in Western Saudi Arabia.
AB  - OBJECTIVE: To determine the seroprevalence of antibodies to hepatitis B virus
      (HBV) and hepatitis A virus (HAV) among children in Jeddah, Kingdom of Saudi
      Arabia (KSA) and to evaluate the need of anti-HAV mass vaccination. METHODS: This
      study was carried out on random samples of schools located at different regions
      in Jeddah, KSA during the year 2004. A total of 527 sera, (285 males and 242
      females), collected from children aged (4-14 years) were tested for anti
      hepatitis B surface (antigen) (HBsAb) and anti-HAV viruses antibodies by enzyme
      linked immunosorbent assay technique. RESULTS: Approximately 98% of children
      received HBV while 49% of received HAV vaccine. For HBV the overall
      seropositivity was 75% while HAV was 28.7%, whereas seronegativity was 14% for
      HBV and 70.5% for HAV. Percentage of seropositivity against HBV was elevated in
      vaccinated versus non-vaccinated children (p < 0.000). In vaccinated children
      against HBV, percentage of seropositivity was elevated in children attending
      public versus those attending private and no schools (p < 0.000) and in Saudi
      versus non-Saudi children (p < 0.05). In vaccinated and non-vaccinated children
      against HAV, percentage of seropositivity was elevated in children attending
      public versus those attending private schools (p < 0.000) and no schools (p <
      0.000) and in males (p < 0.05) versus females (p < 0.01). In vaccinated children,
      percentage of seropositivity for HBV obtained by age range from 4-6 years was
      78.7%, for 7-11 years 74.4% and for 12-14 years 72.6%, whereas for HAV virus,
      seropositivity was 14.8% for 4-6 years, 38.3% for 7-11 years and 28.6% for 12-14
      years. CONCLUSION: Despite successful coverage of mass vaccination against HBV
      among school aged children, in Jeddah, KSA, there are high prevalence levels of
      seronegative with increasing age suggesting outbreak of disease among adolescent.
      Low prevalence of protective antibodies against HAV in vaccinated and non
      vaccinated children may suggest application of mass vaccination program.

PMID- 17013475
TI  - The pattern of fetal hemoglobin changes in patients with malignancy on
      chemotherapy.
AB  - OBJECTIVE: Production of fetal proteins by malignant tissue is a recognized
      phenomenon seen in many neoplastic disorders. Hence, the aim was to determine if
      there is a positive correlation between administration of chemotherapy and
      reduction in fetal hemoglobin (HbF) levels. METHODS: In a prospective study at
      the University of Benin Teaching Hospital, Nigeria, 50 cancer patients at various
      stages of the disease and 50 controls for 10 months period (March to December,
      2005), HbF was determined in pre- chemotherapy (n = 23) and post-chemotherapy (n
      = 27) cancer patients. Fetal hemoglobin was estimated by the modified Betke's
      method. RESULTS: A total of 20 patients (40%) comprising 10 pre-chemotherapy and
      10 post-chemotherapy patients presented with increased HbF which was
      statistically significant (p < 0.0001). There was also a significant decrease in
      post- chemotherapy result when both pre and post-chemotherapy values were
      compared (p = 0.0073). CONCLUSION: The results presented indicate that during
      recovery of erythropoiesis some erythroblasts synthesized HbF and there was a
      reduction following administration of chemotherapy.

PMID- 17013476
TI  - Second trimester cardiac output and its predictive value for preeclampsia.
AB  - OBJECTIVE: To predict women at risk of preeclampsia in the second trimester by
      the assessment of maternal cardiac output (CO). METHODS: Between October 2001 to
      November 2003, we carried out a cross-sectional, prospective, hospital-base study
      in Shiraz University of Medical Sciences, Shiraz, Iran. Cardiac output was
      measured in 102 normotensive women at gestational age 19-25 weeks by Doppler
      echocardiography. Patients with CO >7.4 L/min were considered high risk group
      (Group 1) and those with CO < or =7.4 L/min were in Group II. They were followed
      up until delivery and the incidence of preeclampsia was determined in both
      groups. RESULTS: Twenty percent (6/30) of patient in Group 1, and 1.4% of
      patients in group II developed preeclampsia (p < 0.003). A cut off point of 7.34%
      L/min was chosen for prediction of preeclampsia that showed 85.7% sensitivity,
      74.2% specificity with a negative predictive value of 98% and positive predictive
      value of 20%. CONCLUSION: Cardiac out put is significantly elevated in
      preclinical state of preeclampsia. Echocardiography is a non-invasive method to
      evaluate the maternal homodynamic during the second trimester and can help to
      identify high-risk patient before the development of preeclampsia, thereby it may
      improve the outcome of pregnancy.

PMID- 17013477
TI  - Myocardial bridge. Surgical outcome and midterm follow up.
AB  - OBJECTIVE: To investigate the results of surgery and long-term follow up in 26
      patients who were symptomatic due to myocardial bridge. METHODS: From 1999-2004
      more than 18800 coronary angiography were performed in the Shahid Madani Heart
      Hospital, Tabriz, Iran. Of these, 290 (1.5%) cases had angiographic diagnosis of
      myocardial bridge. Out of the 290 cases, 26 (9%) patients underwent surgical
      myotomy for treatment of myocardial bridge causing significant systolic arterial
      compression. Patients were examined with radio nucleotide study preceding
      angiography that was positive for ischemia and we found 20 cases (76%). Coronary
      angiography and left heart catheterization in all patients revealed impaired
      blood flow due to myocardial bridge in left anterior descending artery and there
      was an additional atherosclerotic stenosis of coronary arteries in 6 and mitral
      valve disease in one patient. Supra arterial myotomy was performed in all
      patients. RESULTS: We observed no mortality or major intraoperative complication.
      Postoperative scintigraphic and angiographic studies demonstrated restoration of
      coronary blood flow and myocardial perfusion without significant residual
      compression of the artery except in one patient who had recurrent anginal chest
      pain after operation and coronary angiography showed residual narrowing in the
      left anterior descending despite myotomy and underwent coronary artery bypass
      graft of left internal mammary artery (LIMA) to distal left anterior descending.
      During 7-81 months of follow-up (mean 34.2 + or = 21), only 2 patients had
      symptoms of angina that was not shown significant residual compression and
      symptoms were controlled by medical treatment. CONCLUSION: The surgical relief of
      myocardial ischemia due to myocardial bridge can be accomplished with low
      operative risk and excellent mid term result.

PMID- 17013478
TI  - Surgical treatment of chronic sacrococcygeal pilonidal sinus. Open method versus
      primary closure.
AB  - OBJECTIVE: To study the comparison between the primary closure and open technique
      after excision of chronic sacrococcygeal pilonidal sinus. METHODS: A randomized
      study was designed and 77 patients with chronic sacrococcygeal pilonidal sinus
      were included in this study. This study took place in Rizgary Teaching Hospital,
      Erbil, Kurdistan, Iraq, from January 1997 to August 2003. The patients were
      separated into 2 groups; Group A (37 patients) were treated by open method
      (excision and healing by secondary intention) and Group B (40 patients) for whom
      primary midline suturing was performed after excision of the pilonidal sinus. The
      follow up ranged from 1.5-5.5 years (mean 4.16) was through outpatient visits.
      RESULTS: The Student t test was applied for statistical analysis for the
      operating time, hospital-stay, time off from work and wound healing time; and the
      results show extremely significant differences between the 2 groups (p < 0.0001).
      The statistical analysis of the total number of postoperative complications of
      both techniques showed a significant difference (p = 0.0401), while the
      differences were insignificant for each complication when analyzed separately.
      CONCLUSION: Excision and primary closure for chronic sacrococcygeal pilonidal
      sinus is superior to excision and healing by secondary intention. We believe that
      primary midline suturing is a useful method for management of chronic
      sacrococcygeal pilonidal sinus.

PMID- 17013479
TI  - Post hemorrhoidectomy pain. A randomized controlled trial.
AB  - OBJECTIVE: To compare the effect of metronidazole on post conventional
      hemorrhoidectomy pain in patients with third and fourth degree hemorrhoids.
      METHODS: Two hundred consecutive patients admitted in King Fahad Hospital, Hofuf,
      Saudi Arabia between June 2002 and May 2004 for surgical treatment of 3rd and 4th
      degree hemorrhoids were randomly assigned into 2 groups. In Group 1 (100
      patients) pre and postoperative metronidazole was used and in Group 2 (100
      patients) no medications were given. All patients received castor oil from 2 days
      before surgery and lactulose after surgery for 2 weeks. Patients were discharged
      home when free of pain. RESULTS: Patients in group 1 had significantly less pain
      than those in the second group. Hospital stay and time to first bowel motion were
      not significantly different between both groups and, early and late complications
      appear similar. Return to normal activity was significantly shorter in the
      metronidazole group. CONCLUSION: Prophylactic metronidazole in Milligan-Morgan
      hemorrhoidectomy is associated with less pain and earlier return to normal
      activity.

PMID- 17013480
TI  - Neurological manifestations of Behcet's disease.
AB  - OBJECTIVE: To determine the prevalence, clinical manifestations, and laboratory
      features of Neuro-Behcet's disease. METHODS: This prospective study was carried
      out in the Behcet's Research Clinic in Shiraz (south-west Iran) and included the
      patients referred from 1990-1999. The patients' clinical records, images, CSF
      analyses, and electrodiagnostic studies were reviewed. RESULTS: Eighteen (15
      males and 3 females) out of 690 Behcet s patients (2.6%, 95% CI = 1.4-3.8%) were
      found to have neurological involvement. The mean +/- standard deviation age of
      these patients was 34.7 +/- 8.6 years. All fulfilled the criteria of the
      International Study Group of Behcet s Disease. Central nervous system involvement
      was more common than peripheral nervous system manifestations. Headache,
      weakness, tingling, and numbness were the most common symptoms. Hyperreflexia,
      upward plantar reflex, and somatosensory findings were the most frequent signs.
      Hemispheral and brainstem stroke-like syndromes and cerebral venous thrombosis
      were the major neurologic presentations. There were also cases of myelitic, pure
      meningoencephalitic, amyotrophic lateral sclerosis-like, multiple sclerosis-like,
      and Guillain Barre syndromes. CONCLUSION: Neuro-Behcet's disease must be
      considered in the differential diagnosis of stroke in young adults, chronic
      meningitis, intracranial hypertension, multiple sclerosis, myelopathies, and
      peripheral neuropathies.

PMID- 17013481
TI  - Bifrontal decompressive craniotomy for malignant brain edema.
AB  - OBJECTIVE: To review the outcome of bifrontal decompressive craniotomy used for
      the treatment of malignant brain edema due to different etiologies. METHODS: The
      study was carried out at King Khalid University Hospital, Riyadh, Kingdom of
      Saudi Arabia during the period from January 2000 to June 2005, and included all
      patients who had malignant brain edema due to different etiology and were treated
      with bifrontal decompressive craniotomy after failure of aggressive medical
      treatment. RESULTS: Ten patients were included in the study, 6 males and 4
      females; the mean age was 24 years. Seven patients had severe head injury, 2 had
      aneurysmal subarachnoid hemorrhage, and one had large calcified olfactory groove
      meningioma. Clinically, all patients, except one, had Glasgow coma scores more
      than 3 before surgery, and operation was performed in all patients once clinical
      deterioration was observed and diagnosis confirmed by CT brain scan. The outcome
      of surgery was good in 70%, poor in 20%, and mortality was 10%. The mean hospital
      stay was 85 days. CONCLUSION: Bifrontal decompressive craniotomy offers immediate
      reduction of intracranial pressure to its normal levels, and improves the outcome
      of malignant brain edema whatever its cause, it should be performed once clinical
      deterioration is observed.

PMID- 17013482
TI  - Initial linguistic and psychometric validation of the Arabic version of Nepean
      Dyspepsia Index.
AB  - OBJECTIVE: To report the initial evaluation of the linguistic and psychometric
      validation of the Nepean Dyspepsia Index (NDI), as part of the ongoing research
      of quality of life among dyspeptic patients. METHODS: The Arabic version of the
      NDI was administered to 158 subjects (54 with non-ulcer dyspeptic [NUD]), 50 with
      gastro-esophageal reflux disease (GERD) and 54 with no history of gastroenteritis
      disease), with a mean age of 46.6 and SD 10.7. All subjects answered the Arabic
      versions of the General Health Questionnaire (GHQ), the Self-Report Questionnaire
      (SRQ), and the Short Form-12 Quality of Life (QOL) scale. We administered the
      final translation of the NDI by consensus. The study was conducted in King Fahad
      Hospital of the University, Al-Khobar, Saudi Arabia, between December 2002 and
      January 2004. RESULTS: The NDI has shown adequate internal consistency. Cronbach
      Alpha coefficient ranged between 0.88 to 0.93, and Split-half correlation
      reliability ranged between 0.82 and 0.94. Correlations between NDI subscales and
      total scores were high and significant. Adequate Face and content validity was
      demonstrated by consultation with gastroenterologists and clinical psychologists.
      Convergent validity was shown in the moderate and significant correlation of the
      NDI subscales and global index with the indices of the SF-12. Divergent validity
      was shown in that subscales of the NDI revealed low correlation with scales which
      measure other dimensions; thus, both QOL subscales and symptom checklist have
      discriminated patients from non-patients groups (p > 0.01). The factorial
      structure of the NDI was also examined, and it revealed 4 factors, which is
      similarly the same with other studies. CONCLUSION: The initial validation of the
      Arabic version of the NDI has shown that this scale has adequate psychometric and
      linguistic property and can represent a good addition to health outcome measures
      in dyspepsia research. Further validation studies are recommended.

PMID- 17013483
TI  - Factors influencing retinoblastoma patients/siblings compliance with clinic
      appointments.
AB  - OBJECTIVE: To investigate the compliance and non-compliance of retinoblastoma
      patients/siblings with their appointments at the Retinoblastoma Clinic in the
      Pediatric Division of a tertiary eye care center, and to evaluate the
      contributing factors. METHODS: This descriptive type of case series was conducted
      between May 1999 and May 2002 at the Retinoblastoma Clinic of King Khaled Eye
      Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. Retinoblastoma
      patients/siblings were surveyed when they attended the clinics. Each family was
      interviewed with the help of a close-ended questionnaire. The sample of patients
      and their siblings were selected based on inclusion and exclusion criteria, and
      their charts were reviewed. RESULTS: The study included 260 retinoblastoma
      patients and their siblings, 134 (51.5%) were males, and 126 (48.5%) were
      females. One hundred and forty-seven (56.5%) of the retinoblastoma
      patients/siblings in the sample were scheduled for follow up. One hundred and
      sixty-eight (64.6%) of retinoblastoma families were contacted by phone and
      reminded of their children's appointments, 37 (14.2%) were not contacted, and for
      55 (21.2%) of the sample subjects, it was not known whether contact was made or
      even attempted. The compliance rate was 86.2%. One hundred and ninety-five
      (95.1%) of non-contacted patients/siblings' families attended subsequently. One
      hundred and thirty-six (52.3%) felt they faced barriers to treatment. Sixty-eight
      (26.2%) completed treatment, and 175 (67.3%) were still being followed up in the
      Retinoblastoma Clinic. Six factors were found to influence compliance with clinic
      appointments: type of appointment, frequency of no shows per clinic, frequency of
      no shows per patient/sibling, number of non-contacted patients/siblings,
      telephone contact, and patients with no contact details. CONCLUSION: There was a
      high compliance rate among those scheduled for check up or follow-up. Family
      education and continuous updating of patients' phone contact numbers can overcome
      non-compliance and maximize the benefits of the phone call mechanism. Factors
      affecting compliance found in this study should be used for improving the
      compliance rate.

PMID- 17013484
TI  - School backpack. How much load do Saudi school boys carry on their shoulders?
AB  - OBJECTIVE: To investigate the percentage of body weight represented by school
      backpacks, to determine the dimensions of school packs, and to identify the
      methods of carrying book bags by elementary school boys. METHODS: A cross
      sectional study, using a multistage random sampling technique, was conducted
      during the Spring of 2005. Six elementary schools from Riyadh were included
      involving 702 Saudi boys in grade 1-6. Measures included body mass, height,
      biacromial and bi-iliac breadths, triceps and subscapular skinfolds, calculated
      fat percentage, school bag weight and dimensions. Students were also asked to
      respond to questions related to how they travel to and from school, how they
      carry the bag, and if they have pain due to bag carriage. RESULTS: Body fat
      percentage increased from 14.2% in the first graders to 24.6% in the sixth
      graders. The increase in body dimensions, however, was less than the increase in
      the fat percentage. School bag averaged 3.2 kg in absolute weight and 10.7%
      relative to student's body mass. Nearly 50% of the sample carried backpacks
      weighing more than 10% of their weight. Bag surface area averaged 1.05 m2 while
      the ratio of bag surface area to student's trunk area ranged from 129% in the
      first graders to 81% in the sixth graders. Approximately 29% of the students walk
      to and from school. More than 65% of the sample carried their bags over one or 2
      shoulders, 20% used single strap bags carried by one hand and 14.5% had bags with
      wheels. Over one third of the students reported experiencing bodily pain due to
      bag carriage. CONCLUSION: A considerable proportion of Saudi school boys carried
      an overloaded and oversized backpacks. Moreover, one third of the sample
      experienced bodily pain related to school bags. It is recommended that school
      bags be limited to no more than 5-10% of student's body weight.

PMID- 17013485
TI  - An epidemiological study of enuresis among primary school children in Isfahan,
      Iran.
AB  - OBJECTIVE: To estimate the prevalence of enuresis in primary school children in
      Iran and to determine the factors associated with this disorder. METHODS: A cross
      sectional time-ordered study was performed at the Faculty of Medicine, Isfahan
      Medical University, Isfahan, Iran from September 2005 to January 2006. A total of
      4500 self-administered questionnaires were distributed to parents of children
      aged 6-12 years attending 30 primary schools. RESULTS: From an overall response
      rate of 69.9%, enuresis was reported in 216 children (7%), comprising 6.2% for
      nocturnal enuresis according to ICD10 and 3.3% according to DSM IV, 0.5% for
      diurnal enuresis and 0.8% for combined day and night wetting. Primary nocturnal
      enuresis was reported in 166 children (5.3%). Seventy-one (50.7%) of the 140
      children with nocturnal enuresis had > or =3 wet nights per week. A positive
      family history in father and mother was seen in 51% and 39% of children with
      primary nocturnal enuresis respectively. Using logistic regression analysis,
      younger age (p < 0.002), gender (p < 0.0001) and low level of education of mother
      (p < 0.028) were significant predictors of enuresis. Positive history of enuresis
      in father was a significant predictor of primary nocturnal enuresis (p < 0.012).
      CONCLUSION: The prevalence of nocturnal enuresis in Iran is lower than those
      reported in western countries, however, higher percentage demonstrated severe
      enuresis. The prevalence of diurnal enuresis is lower than previous studies. Age,
      gender and the educational level of the mother are the main risk determinants of
      enuresis and the prevalence of primary nocturnal enuresis appears to be
      significantly related to positive history of enuresis in father.

PMID- 17013486
TI  - Nager's acrofacial dysostosis with hypertrophic cardiomyopathy.
AB  - Nager syndrome is a rare condition associated with craniofacial malformations
      such as, micrognathia, zygomatic hypoplasia, external ear malformations, and
      preaxial limb deformities. This report features a case of Nager syndrome
      occurring in a one-year-old boy showing microretrognathia, thumb hypoplasia,
      brachydactyly, hexadactyly, and hypertrophic cardiomyopathy, characteristics not
      usually encountered in published cases.

PMID- 17013487
TI  - Reversible pulmonary hypertension post adenotonsillectomy.
AB  - An 18-month-old boy presented with signs and symptoms of obstructive sleep apnea
      and pulmonary hypertension of 12 months duration. Confirmatory laboratory
      studies, in the form of echocardiography and overnight oximetry, were carried
      out, which showed hypoxemia and severe pulmonary hypertension. He had
      adenotonsillectomy, which resulted in complete resolution of signs and symptoms
      of pulmonary hypertension. Chronic upper airway obstruction should not be
      overlooked as it is a reversible cause of pulmonary hypertension.

PMID- 17013488
TI  - Metastatic gastrointestinal stromal tumor and hypercalcemia in a patient with
      ulcerative colitis.
AB  - A 45-year-old man suffering from intermittent rectal bleeding was diagnosed with
      ulcerative colitis involving the descending colon and rectum. After 2 years on
      ulcerative colitis treatment, he presented with metastatic gastrointestinal
      tumor, liver and peritoneal spread, and a pelvic mass. Interestingly, he was
      found to have significant hypercalcemia. He was treated with Imatinib with
      significant symptomatic and clinical response.

PMID- 17013489
TI  - Co-existence of spontaneous splenic rupture and tuberculosis of the spleen.
AB  - A rare case of splenic tuberculosis complicated by splenic rupture is reported. A
      73-year-old man, hospitalized for peptic ulcer bleeding, presented in oligemic
      shock, was transferred to the operating room. Hemoperitoneum, due to rupture of
      an enlarged spleen was detected. The pathology revealed splenic tuberculosis. He
      had an uneventful recovery. Postoperatively, he received a combination of anti
      tuberculous therapy for 6 months.

PMID- 17013490
TI  - Traumatic pseudoaneurysm from the aorta to the left common carotid artery
      presenting as widened mediastinum.
AB  - Diagnosis of pseudoaneurysm of the aorta or its main branches is a challenge in
      patients with blunt chest trauma. Computed tomography helps to demonstrate
      intrathoracic hemorrhage and suspected great vascular injury when a chest
      radiograph reveals widening of the mediastinum. Aortic angiography remains the
      gold standard in the determination of the site, and severity of vascular injury
      for definitive surgical intervention. Timing of surgical repair is controversial.
      Delayed repair of traumatic pseudoaneurysm of the aorta after primary control of
      associate injuries decreases mortality significantly, thus improving prognosis.
      We report a case of successful repair of a traumatic pseudoaneurysm of the aortic
      arch with extension to the left common carotid artery in an 18-year-old female
      patient. The diagnosis, surgical approaches, and timing of operation are
      discussed along with case presentation.

PMID- 17013491
TI  - Extra-adrenal composite pheochromocytoma-ganglioneuroma.
AB  - Composite tumors containing pheochromocytoma and ganglioneuroma are rare tumors
      typically arising in the adrenal glands. Very few were reported outside of the
      adrenals. We present the case of a middle-aged woman with a retroperitoneal mass
      that was discovered when she complained of local signs of compression and
      systemic signs of catecholamine hypersecretion. On pathology the mass was
      composed of large polygonal and pleomorphic cells arranged in nests
      characteristic of pheochromocytoma that were mixed with clusters of mature
      ganglion cells and bundles of spindle cells characteristic of ganglioneuroma. The
      histological features were benign, but due to its invasion of the inferior vena
      cava and of the right renal artery, we had concerns about the malignant potential
      of the pheochromocytoma component, which is extremely rare in these composite
      tumors.

PMID- 17013492
TI  - Colchicine poisoning in a very young child.

PMID- 17013493
TI  - Tonsure alopecia on the wrists. Unreported site of trichotillotic and relation
      with unemployment.

PMID- 17013494
TI  - Abnormal intra-parotid origin of the facial artery.

PMID- 17013495
TI  - Qur-an, human embryology and nutrition.

PMID- 17013496
TI  - Environmental malignant pleural mesothelioma in Southeast Turkey.

PMID- 17013497
TI  - Role of methylprednisolone in un-resolving cases of acute respiratory distress
      syndrome.

PMID- 17013498
TI  - Cross-leg fasciocutaneous flaps. Still a valid option for reconstruction of
      traumatic lower extremity defects.

PMID- 17013499
TI  - Outcome of occlusion treatment for strabismic amblyopia in children below 12
      years old.

PMID- 17013500
TI  - Botulinum toxin as an alternative for the treatment of aesthetic deformities.

PMID- 17013501
TI  - Dietary intake and nutritional status of Turkish pregnant women during Ramadan.

PMID- 17013502
TI  - Fungal ball in a cavity.

PMID- 17013503
TI  - Surgery from experimental research to clinical application and vice-versa.

PMID- 17013504
TI  - New photonic technologies for the treatment and diagnosis of hepatic diseases: an
      overview of the experimental work performed in collaboration, between Physics
      Institute of Sao Carlos and Ribeirao Preto Faculty of Medicine of the University
      of Sao Paulo.
AB  - Recent advances in optical techniques have created a great range of possibilities
      for diagnosis and therapeutics in liver related diseases. With the uses of
      efficient light sources like lasers and LEDs (Light Emitting Diodes) it is
      possible to employ the light-tissue interaction to promote hepatic tissue
      regeneration after partial hepatectomy, to detect hepatocarcinoma and steatosis
      by utilizing optical fluorescence, to evaluate the metabolism of the liver during
      hepatic transplantation as well as to treat liver tumors. We present here an
      overview of the technique presently in development at the Ribeirao Preto Faculty
      of Medicine-USP in cooperation with the Physics Institute of Sao Carlos-USP. The
      results obtained so far have been the subject of a list of publications and are
      here presented as an overview. A new perspective for modern application of
      optical techniques in different medical practices related to the liver is
      presented.

PMID- 17013505
TI  - Liver transplantation: expectation with MELD score for liver allocation in
      Brazil.
AB  - Liver transplantation represents the most effective therapy for patients
      suffering from chronic end-stage liver disease. Until very recently, in Brazil,
      liver allocation was based on the Child-Turcotte-Pugh score and the waiting list
      followed a chronological criterion. In February 2002 the Model for End-stage
      Liver Disease (MELD) score was adopted for the allocation of donor livers in the
      US. After that change, an increased number of patients with more severe liver
      disease was observed, although there was no difference in 1-year patient and
      graft survival. A reduction in waiting-list mortality was also observed. In
      Brazil, the MELD score was adopted on May 31st, 2006. Good results are expected
      regarding the new criterion for allocation.

PMID- 17013506
TI  - Hepatitis C: a challenge to hepatologists and to the liver transplantation team.
AB  - Hepatitis C is the main cause of cirrhosis and hepatocellular carcinoma and the
      leading indication of liver transplantation. The aim of this article was to
      review specific epidemiological, clinical and therapeutic aspects of hepatitis C
      and their implication for the hepatologists belonging to liver transplantation
      services. These specific aspects were reviewed in the literature mainly using
      Medline. Data regarding the epidemiological, clinical and therapeutic aspects of
      hepatitis C are discussed, with emphasis on their consequences for the liver
      transplantation team. Hepatitis C is a challenge for hepatologists and for the
      liver transplantation team. The burden we observe today is the late consequence
      of infection that occurred in the past. Measures for early recognition of
      complications of liver disease are recommended. HCV treatment should always be
      performed before liver transplantation if possible, but if not, HCV recurrence
      should be recognized and treated early after transplantation.

PMID- 17013507
TI  - Pyruvate kinase activation and lipoperoxidation after selective hepatic ischemia
      in Wistar rats.
AB  - PURPOSE: Hepatic ischemia and reperfusion can cause several problems in hepatic
      surgery. The aim of this study was to determine pyruvate kinase activation and
      lipid peroxidation after hepatic ischemia. METHODS: Twenty-four Wistar rats were
      submitted to 90 minutes of selective liver ischemia and 15 minutes of
      reperfusion. Twelve animals were submitted to selective liver ischemia and
      reperfusion (Group A) and the other 12 were submitted to sham operation (Group
      B). After 15 minutes of reperfusion, the following parameters were measured: mean
      arterial pressure (MAP), alanine aminotransferase (ALT), glycemia (GLY), hepatic
      glycogen (GH), pyruvate kinase (PK) activation, hepatic glutathione (GSH) and
      malondialdehyde (MDA). Analysis of the results were made by the Student t-test
      and has been considered significant difference for p<0.05. RESULTS: A and B were
      differents for all parameters analized. CONCLUSION: The animals of group A showed
      reperfusion syndrome with a fall in MAP, activation of glycid metabolism through
      the glycolitic pathway and presence of lipid peroxidation compared to group B.

PMID- 17013508
TI  - Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic
      ischemia/reperfusion injury.
AB  - PURPOSE: The main aim of this study was to determine the influence of ischemic
      preconditioning (IPC) on rat liver cirrhosis. METHODS: Cirrhosis was induced in
      Wistar rats by occlusion of the hepatic duct. The animals were divided into four
      groups of six animals each: non-cirrhotic group (simulated operation only),
      cirrhotic control group (simulated operation in cirrhotic rats), I/R group (40
      minute ischemia without IPC), and IPC group (cirrhotic rats with ischemia,
      previously submitted to IPC). The IPC procedure consisted of partial hepatic
      ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of
      the IPC group, the animals were submitted to liver ischemia for 40 minutes after
      the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples
      were collected for measurement of serum aminotransferases (ALT and AST). The
      respiratory control ratio (RCR), the mitochondrial membrane potential (MMP), and
      malondialdehyde (MDA) values in the hepatic tissue were analyzed. Nonparametric
      statistical analysis was used and a value of p<0.05 was considered statistically
      significant. RESULTS: Ischemia did not induce significant increase in ALT and AST
      levels. MDA values were significantly higher in cirrhotic animals. MMP did not
      significantly change in cirrhosis and liver ischemia. Mitochondrial RCR decreased
      in liver cirrhosis, accentuated upon liver ischemia, and did not significantly
      change with IPC. CONCLUSION: Ischemic preconditioning does not protect the liver
      from hepatic injury induced by the ischemia/reperfusion process.

PMID- 17013509
TI  - The effect of laser on remanescent liver tissue after 90% hepatectomy in rats.
AB  - PURPOSE: To evaluate the effect of laser beam on reminiscent liver after partial
      hepatectomy 90%. METHODS: Wistar rats, (N=42), were divided into six groups with
      seven specimens each. The partial hepatectomy (HP) was performed in all animals
      through exeresis of approximately 90% of the liver parenchyma. The animals from
      groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser
      irradiation carried out through application (dose of 22.5 J/cm2) in five
      different sites in the reminiscent liver. The rats were then sacrificed 24, 48
      and 72 hours after HP procedure, for the liver regeneration analysis,using the
      Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum
      aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of
      alanine aminotransferase for the group of 24 hours and a decrease for the group
      of 72 hours exposed to laser. The index of marked cells had a considerable more
      improvement for the group of 72 hours exposed in laser compared to other groups.
      CONCLUSION: Laser did not cause hepatic injuries additional to the partial
      hepatectomy and perhaps led to a benefit by stimulating the proliferative
      activity.

PMID- 17013510
TI  - Proliferative effect of the aqueous extract of Hyptis pectinata on liver
      regeneration after partial hepatectomy in rats.
AB  - PURPOSE: This study was carried out to assess the effects of the aqueous extract
      of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT
      and gamma-GT) after 67% partial hepatectomy in rats. METHODS: AST, ALT and gamma
      GT, were determined by conventional procedures using a spectrophotometer (Model
      E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for
      proliferating cell nuclear antigen (PCNA). RESULTS: Oral pretreatment during 4
      days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was
      statistically decreased in comparison to the group submitted to distilled water
      administration. The other enzymes assessed disclosed no difference when all
      groups were compared. CONCLUSION: The present study shows that the aqueous
      extract of Hyptis pectinata leaves contains some biological active principles
      that stimulate liver regeneration at 100 mg/kg and cause slight hepatic
      protection at 200 mg/kg.

PMID- 17013511
TI  - Effect of the aqueous extract of Sida cordifolia on liver regeneration after
      partial hepatectomy.
AB  - PURPOSE: The use of medicinal plants for the treatment of human diseases has
      increased worldwide. Many of them are used by oral administration and, after
      absorption, may affect many organs. Therefore, this study aimed at assessing the
      effects of the aqueous extract of Sida cordifolia leaves, popularly known in
      Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were
      divided into four groups: control, Sida100, Sida200 and Sida400 groups. All
      animals were submitted to oral administration of distilled water, 100, 200 and
      400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately
      after this, they underwent 67% partial hepatectomy. Twenty four hours later,
      their livers were removed. Hepatic regeneration was assessed by
      immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using
      the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed
      higher liver regeneration indices than control group (p<0.001 and p<0.05,
      respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates
      liver regeneration after 67% partial hepatectomy in rats.

PMID- 17013512
TI  - Psychological distress in patients listed for liver transplantation.
AB  - PURPOSE: To assess the level of depression in patients listed for liver
      transplantation. METHODS: Sixty-four adult patients, listed for liver
      transplantation, were submitted to psychological evaluation, including assessment
      of depression by means of the Beck Depression Inventory. RESULTS: Twenty-two
      percent of the patients had mild/major depression. The group consisted mainly of
      male patients aged 47 on average, with a history of alcohol abuse and a Meld
      (Model for End-Liver Disease) value of 14.5. Patients that had been awaiting
      liver transplant longer presented less severe liver disease according to the
      Child-Pugh criteria. CONCLUSION: It is extremely important to assess
      psychological distress in patients listed for liver transplantation. An
      interdisciplinary approach is essential to improve the patients' quality of life
      both in the pre- and post-transplant periods.

PMID- 17013513
TI  - Impact of blood salvage during liver transplantation on reduction in transfusion
      requirements.
AB  - PURPOSE: The aim of this study was to analyse the changes in transfusion
      requirements, in patients submitted to orthotopic liver transplantation from
      cadaveric donors, with the use of intraoperative red blood cell salvage (Cell
      Saver). METHODS: Data from 41 transplants were analysed. Intraoperative blood
      loss was calculated from the cell salvage, suction and the swabs. The autologous
      and heterologous transfusions were recorded The red blood salvage was performed
      using the Cell Saver 5 System (Haemonetics). For analysis the patients were
      divided in two groups: one that used the Cell Saver and another that didn't.
      RESULTS: The median age of the patients was 50 years and the main indication for
      liver transplantation was cirrhosis (35 cases-85.3%). The median blood loss was
      8362+3994 ml (with the Cell Saver) and 10824+7002 ml (without the Cell Saver) and
      the median transfusion of heterologous packed red blood cells was 9.6+8 units
      (with the Cell Saver) compared to 22.3+21 units (without the Cell Saver).
      CONCLUSIONS: The Cells Saver has the potential to reduce the need for
      heterologous blood transfusion reducing the risks of transmissible diseases.

PMID- 17013514
TI  - Hepatic microcirculatory failure.
AB  - Liver ischemia has been considered a frequent problem in medical practice, and
      can be associated to a number of surgical and clinical situations, such as
      massive hepatic resections, sepsis, liver trauma, circulatory shock and liver
      transplantation. After restoring blood flow, the liver is further subjected to an
      additional injury more severe than that induced by ischemia. On account of the
      complexity of mechanisms related to pathophysiology of ischemia and reperfusion
      (I/R) injury, this review deals with I/R effects on sinusoidal microcirculation,
      especially when steatosis is present. Alterations in hepatic microcirculation are
      pointed as a main factor to explain lower tolerance of fatty liver to ischemia
      reperfusion insult. The employment of therapeutic strategies that interfere
      directly with vasoactive mediators (nitric oxide and endothelins) acting on the
      sinusoidal perfusion seem to be determinant for the protection of the liver
      parenchyma against I/R. These approaches could be very suitable to take advantage
      of marginal specimens as fatty livers, in which the microcirculatory
      disarrangements hamper its employment in liver transplantation.

PMID- 17013515
TI  - Liver cirrhosis and hepatic stellate cells.
AB  - The cirrhosis represents the final stage of several chronic hepatic diseases and
      it is characterized by the presence of fibrosis and morphologic conversion from
      the normal hepatic architecture into structurally abnormal nodules. In the
      evolution of the disease there is loss of the normal vascular relationship and
      portal hypertension. There are also regenerative hepatocellular alterations that
      become more prominent with the progression of the disease. The liver
      transplantation continues to be the only therapeutic option in cases of disease
      in terminal phase. The hepatic stellate cells (HSC) are perisinusoidal cells that
      store vitamin A and produce growth factors, citocins, prostaglandins and other
      bioactive substances. They can suffer an activation process that convert them to
      cells with a phenotype similar to myofibroblasts. When activated, they present
      increased capacity of proliferation, mobility, contractility and synthesis of
      collagen and other components of extracellular matrix. They possess cytoplasmic
      processes adhered to sinusoids and can affect the sinusoidal blood flow. HSC are
      important in pathogenesis of fibrosis and portal hypertension.

PMID- 17013516
TI  - A molecular view of liver regeneration.
AB  - The purpose of this review was to carry out an analysis of the liver regenerative
      process focusing on the molecular interactions involved in this process. The
      authors undertook a review of scientific publications with a focus on the liver
      regeneration. The cellular processes involved in liver regeneration require
      multiple systematic actions related to cytokines and growth factors. These
      interactions result in the initiation of mitogenic potential of the hepatocytes.
      The action of these modulators in the regenerative process require a processing
      in the extra-cellular matrix. Serines and metal proteins are responsible for the
      bio availability of cytokines and growth factors so that they can interact as
      receptors in the cellular membrane generating signaling events for the beginning
      and end of the liver regenerative process. The exact mechanism of interaction
      between cells, cytokines and growth factors is not well established yet. A series
      of ordered events that result in the hepatic tissue regeneration has been
      described. The better understanding of these interactions should provide a new
      approach of the treatment for liver diseases, aiming at inducing the regenerative
      process.

PMID- 17013517
TI  - Cellular aspects of liver regeneration.
AB  - This paper has the objective to analyze the cellular aspects of liver
      regeneration (LR). Upon damage in this organ, the regenerative capacity of
      hepatocyte is sufficiently able to reestablish the parenchyma as a whole. Taking
      into account the regenerative capacity of hepatocyte, the need of a progenitor or
      a liver trunk cell was not obvious. Nowadays it is well-established that
      precursor cells take part in the liver regenerative process. The liver trunk
      cell, oval cell, acts as a by-potential precursor, contributing for the liver
      restoration, mainly when the hepatocytes are unable to proliferate. Another
      precursor, trunk cell of hematopoetic origin (HSC), takes part in the
      regenerative process, originating cells of the hepatocytic lineage and
      colangiocytes, as well as the oval cell. The way the trans-differentiation takes
      place is not established yet. A number of studies must be undertaken in order to
      clarify questions, such as the possible occurrence of cellular fusion process
      between the HSC and the hepatic cells and the possibility of application as a new
      therapeutic procedure in the treatment of diseases associated with insufficiency
      of this noble organ.

PMID- 17013518
TI  - Liver disease associated with intestinal failure in the small bowel syndrome.
AB  - The introduction of the Total Parenteral Nutrition (TPN) has given rise to a new
      hope in the treatment of intestinal failure (LF) associated with the Short Bowel
      Syndrome (SBS). However, together with the TPN and the increase of survival of
      these patients, new problems and questions have emerged, as well as new
      therapeutical procedures. Taking into consideration this emerging reality, this
      paper has the purpose to undertake a review of current concepts and available
      treatments for patients with IF associated-liver disease. Although TPN provides
      an increase of survival of patients with intestinal failure, it is a potential
      source of complication such as: septicemia, hyperglycemia, venous thrombosis and
      liver disease. There are several hypothesis conceived to explain the liver
      disease associated to intestinal failure, however the only definite treatment as
      a potential to reverse the non-cirrhotic liver disease is the small intestine
      transplantation. Despite indications for intestine transplantation are not
      entirely defined in literature, the trend is its early indication in high-risk
      patients, preserving the liver integrity and preventing the eventual need of both
      liver and intestine transplantations altogether.

PMID- 17013519
TI  - Nonalcoholic fatty liver disease and obesity.
AB  - PURPOSE: The aim of this review is to update concepts of the nonalcoholic fatty
      liver disease (NAFLD) and to establish a relationship between this condition and
      obesity. METHODS: By means of a comprehensive literature review where special
      attention was devoted to articles published in the last 5 years, NAFLD is
      discussed in view of new concepts, diagnosis, staging, and treatment. RESULTS:
      NAFLD is emerging as one of the main causes of chronic liver disease and it is
      believed to be the hepatic component of the metabolic syndrome, whose central
      features include obesity, hyperinsulinemia, peripheral insulin resistance,
      diabetes, dyslipidemia, and hypertension. The surgical treatment of morbid
      obesity is one of the options available for the treatment of NAFLD. CONCLUSION:
      Nonalcoholic fatty liver disease is strongly related with obesity.

PMID- 17013520
TI  - Chronic liver disease prevention strategies and liver transplantation.
AB  - Chronic liver disease is a considerable burden on society, being one of the three
      main causes of death in certain regions of Africa and Asia. Liver transplant is
      the only treatment option for cirrhosis, which is the end stage of many chronic
      liver diseases. This article reviews the preventable causes of cirrhosis and the
      preventive strategies which could be implemented in order to avoid the
      catastrophic consequences of cirrhosis. With small variations around the world,
      70 to 80% of the end stage liver diseases are caused by excessive alcohol
      consumption and by viral hepatitis, both of which are potentially preventable.
      Excessive alcohol consumption has important public health consequences because of
      its involvement not only with cirrhosis, but also with motor vehicle accidents,
      unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B
      and C have the greatest impact on public health. Effective vaccine is available
      for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus
      C is awaited, effective preventive strategies should be undertaken to avoid the
      preventable cases of end stage liver disease.

PMID- 17013522
TI  - Citizenship and experimental research.

PMID- 17013521
TI  - Hepatic injury.
AB  - Hepatic trauma occurs in approximately 5% of all admissions in emergency rooms.
      The anatomic location and the size of the liver make the organ even more
      susceptible to trauma and frequently in penetrating injuries. The American
      Association for the Surgery of Trauma established a detailed classification
      system that provides for uniform comparisons of hepatic injury. Diagnosis of
      hepatic injury can be sometimes easy; however the use diagnostic modalities as
      diagnostic peritoneal lavage, ultrasound and computed tomography allow faster and
      more accurate diagnosis. Nonoperative management of the hemodynamically stable
      patient with blunt injury has become the standard of care in most trauma centers.
      Few penetrating abdominal lesions allow conservative management; exceptions can
      be some penetrating wounds to right upper abdominal quadrant. Operative treatment
      of minor liver injuries requires no fixation or can only be managed with
      eletrocautery or little sutures. Major liver injuries continue, despite technical
      advances, a challenge to surgeons. Many procedures can be done as direct repair,
      debridement associated to resections, or even in more severe lesions, packing.
      This constitutes a damage control which can allow time to recovery of patient and
      decreasing mortality shortly after trauma.

PMID- 17013523
TI  - The use of premature chromosome condensation to study in interphase cells the
      influence of environmental factors on human genetic material.
AB  - Nowadays, there is a constantly increasing concern regarding the mutagenic and
      carcinogenic potential of a variety of harmful environmental factors to which
      humans are exposed in their natural and anthropogenic environment. These factors
      exert their hazardous potential in humans' personal (diet, smoking,
      pharmaceuticals, cosmetics) and occupational environment that constitute part of
      the anthropogenic environment. It is well known that genetic damage due to these
      factors has dramatic implications for human health. Since most of the
      environmental genotoxic factors induce arrest or delay in cell cycle progression,
      the conventional analysis of chromosomes at metaphase may underestimate their
      genotoxic potential. Premature Chromosome Condensation (PCC) induced either by
      means of cell fusion or specific chemicals, enables the microscopic visualization
      of interphase chromosomes whose morphology depends on the cell cycle stage, as
      well as the analysis of structural and numerical aberrations at the G1 and G2
      phases of the cell cycle. The PCC has been successfully used in problems
      involving cell cycle analysis, diagnosis and prognosis of human leukaemia,
      assessment of interphase chromosome malformations resulting from exposure to
      radiation or chemicals, as well as elucidation of the mechanisms underlying the
      conversion of DNA damage into chromosomal damage. In this report, particular
      emphasis is given to the advantages of the PCC methodology used as an alternative
      to conventional metaphase analysis in answering questions in the fields of
      radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and
      experimental therapeutics.

PMID- 17013524
TI  - Analysis of glutathione and vitamin C effects on the benzenetriol-induced DNA
      damage in isolated human lymphocytes.
AB  - The alkaline single-cell gel electrophoresis (or Comet) assay was applied to
      evaluate the eventual DNA damage induced by the triphenolic metabolite of
      benzene, 1,2,4-benzenetriol (BT), in isolated human lymphocytes. Prior to BT
      treatment, ranging from 5 to 50 microM, a supplementation with glutathione (GSH,
      350 microg/ml) was carried out to assess whether GSH may have a modulating effect
      on the Comet response. The effect of a fixed dose of BT was also evaluated in the
      presence of the exogenous antioxidant vitamin C (40 and 200 microM).
      Additionally, we investigated whether the polymorphism of glutathione S
      transferase T1 (GSTT1) gene may affect the individual level of BT-induced DNA
      damage in vitro. For all donors included in the present study, BT produced a
      significant dose-response relationship. No clear effect of GSH preincubation was
      seen on the BT-induced response. On the contrary, a significant reduction of DNA
      damage was observed in the presence of vitamin C (at least at 200 microM).
      Although our data suggest some individual differences according to the GSTT1
      genotype in the outcome of the Comet assay, a large number of individuals should
      be studied in further investigations to obtain reliable conclusions.

PMID- 17013525
TI  - Genotoxic and antigenotoxic properties of selenium compounds in the in vitro
      micronucleus assay with human whole blood lymphocytes and TK6 lymphoblastoid
      cells.
AB  - Selenium is known to possess both genotoxic and antigenotoxic properties. In the
      present study, we have evaluated the genotoxicity and antigenotoxicity of three
      selenium compounds (sodium selenate, sodium selenite and selenous acid) by
      measuring in vitro micronucleus induction. Assays were conducted in whole blood
      lymphocytes and in the TK6 lymphoblastoid cell line, with and without co
      treatment with potassium dichromate, a known genotoxic compound. In general, the
      compounds were more active in TK6 cells than they were in blood lymphocytes. Only
      1 microM selenous acid increased the frequency of binucleated cells containing
      micronuclei (BNMN) in blood lymphocytes, while all three selenium compounds
      increased BNMN in TK6 cells. In addition, combinations of selenous acid and
      potassium dichromate resulted in lower frequencies of BNMN than potassium
      dichromate alone in blood lymphocytes, while combinations of sodium selenate and
      potassium dichromate produced lower frequencies of BNMN than potassium dichromate
      alone in TK6 cells. The concentrations of selenium compounds that were used, in
      combination with the medium components and the biological physiology of the whole
      blood lymphocytes and TK6 cells, could have affected the redox potential of the
      compounds, switching the chemicals from a pro-oxidant to antioxidant status and
      vice-versa. The lower activities of the compounds in blood lymphocytes may be due
      to the protective effects of blood components. The results indicate that the
      genotoxic and antigenotoxic properties of selenium compounds are highly dependent
      upon the conditions under which they are evaluated.

PMID- 17013526
TI  - Effects of pesticides on occupationally exposed humans.
AB  - Pesticides are known to contain numerous genotoxic compounds; however,
      genotoxicity biomonitoring studies of workers occupationally exposed to
      pesticides have produced variable results. In this study, we employed the Comet
      assay to examine DNA damage in peripheral blood lymphocytes (PBLs) from 64
      greenhouse workers from Almeria in south-eastern Spain in comparison to PBLs from
      50 men from the same area but not engaged in any agricultural work. The results
      indicated that there were no differences in the basal levels of DNA damage in the
      two study groups. In addition, exposure of PBL from the workers and controls to
      hydrogen peroxide or gamma-irradiation led to similar levels of DNA damage; the
      subsequent repair of the induced DNA damage was also similar for both study
      populations. Smoking had no impact on any of the responses. The results of this
      study indicate that the greenhouse workers had no detectable increase in DNA
      damage or alteration in the cellular response to DNA damage compared to our
      control population.

PMID- 17013527
TI  - Genetic damage induced by accidental environmental pollutants.
AB  - Petroleum is one of the main energy sources worldwide. Its transport is performed
      by big tankers following some established marine routes. In the last 50 years a
      total amount of 37 oil tankers have given rise to great spills in different parts
      of the world, Prestige being the last one. After the accident, a big human
      mobilisation took place in order to clean beaches, rocks and fauna, trying to
      reduce the environmental consequences of this serious catastrophe. These people
      were exposed to the complex mixture of compounds contained in the oil. This study
      aimed at determine the level of environmental exposure to volatile organic
      compounds (VOC), and the possible damage induced on the population involved in
      the different cleaning tasks by applying the genotoxicity tests sister chromatid
      exchanges (SCE), micronucleus (MN) test, and comet assay. Four groups of
      individuals were included: volunteers (V), hired manual workers (MW), hired high
      pressure cleaner workers (HPW) and controls. The higher VOC levels were
      associated with V environment, followed by MW and lastly by HPW, probably due to
      the use of high-pressure cleaners. Oil exposure during the cleaning tasks has
      caused an increase in the genotoxic damage in individuals, the comet assay being
      the most sensitive biomarker to detect it. Sex, age and tobacco consumption have
      shown to influence the level of genetic damage, while the effect of using
      protective devices was less noticeable than expected, perhaps because the kind
      used was not the most adequate.

PMID- 17013528
TI  - Evaluating side effects of human exposure to noxious agents.

PMID- 17013529
TI  - Combine cancer gene therapy harnessing plasmids expressing human tumor necrosis
      factor alpha and Herpes simplex thymidine kinase suicide gene.
AB  - We have assessed the effect of combine cancer gene therapy with exogenous human
      tumor necrosis factor alpha (hTNFalpha) and suicide gene therapy on three human
      cancer cell lines MCF-7 (breast adenocarcinoma), U-118MGand 42-MG-BA (human
      gliomas). Transfection of a plasmid containing hTNFalpha under the control of a
      hybrid promoter resulted in expression of hTNFalpha gene in vitro. Transduction
      of retroviral plasmid containing Herpes simplex thymidine kinase (HSVtk) led to
      the expression of thymidine kinase in all three cell lines. MTT cell
      proliferation assay and flow cytometric analysis showed a significant increase in
      apoptotic and necrotic cells and decrease of proliferation in all cell lines
      after combine therapy with hTNFalpha expression plus thymidine kinase/GCV suicide
      system. The presence of these two genes after transduction of retroviral vector
      containing thymidine kinase and hTNFalpha was confirmed by PCR. The expression of
      HSVtk gene was proved by Western blot analysis, and the expression of both genes
      was confirmed by RT-PCR. Additive cell killing effect due to presence of HSVtk
      and hTNFalpha therapeutic genes after activation of non-toxic prodrug was
      observed. Whether the bicistronic plasmid containing both genes would improve the
      therapeutic effect need to be assessed in the future.

PMID- 17013530
TI  - Assay design and optimization of mutant-enriched PCR based method for detection
      of K-ras gene mutations in pancreatic carcinoma.
AB  - The aim of our work was to develop a fast, reliable and sensitive PCR method to
      detect K-ras mutations in various clinical samples. There is a need for an
      unimpeachable method for early diagnosis and/or screening of pancreatic cancer
      (PC). We optimized and subsequently analyzed four methods based on mutant
      enriched PCR for the sensitivity, cost and time expense. Using the selected
      optimal method we examined codon 12 K- ras mutations in a study population of 59
      patients with upper GIT malignancies. Reliability of the genotyping was confirmed
      by sequencing. By using the best of our modified mutant-enriched PCR methods we
      achieved sensitivity of 1:1 x 10(5). Further studies are necessary to determine
      the optimal biological material sampling in PC.

PMID- 17013531
TI  - Significance of tenascin-C, fibronectin, laminin, collagen IV, alpha5beta1 and
      alpha9beta1 integrins and fibrotic capsule formation around liver metastases
      originating from cancers of the digestive tract.
AB  - The formation of a fibrotic capsule around liver metastases may functionally act
      as a barrier to local invasion. However, the prognostic significance of
      exstracellular matrix (ECM) and of some integrins' deposition around liver
      metastases remains unclear. An immunohistochemical investigation was carried out
      on 55 patients with synchronous liver metastases from colorectal and gastric
      cancers. Encapsulated metastases were detected in 60% of the cases. The 'non
      capsular' cases showed clear immunostaining for tenascin-C, fibronectin, collagen
      IV, laminin, alphaSMA and integrins. On opposite, most of the cases with
      'capsule' were negative for the studied ECM proteins and the two integrins. The
      patients with 'capsular' pattern had significantly longer median survival after
      the surgery compared to those with non-encapsulated metastases. The presence of
      tenascin, fibronectin, fibronectin receptor and laminin, as well as the strong
      immune signal for alphaSMA and collagen type IV in the sinusoids attached to the
      liver metastases was associated with a worse prognosis. The cells, forming ECM in
      the sinusoids attached to metastases in the 'non-capsular' pattern were alphaSMA
      positive myofibroblasts. It was shown ultrastructurally that they were HSCs. The
      results indicate that fibrotic capsule formation is associated with longer
      survival after surgery. The appearance of tenascin-C and of its receptor at the
      periphery of liver metastases could be used as a sign of invasiveness.

PMID- 17013532
TI  - Diverse resveratrol sensitization to apoptosis induced by anticancer drugs in
      sensitive and resistant leukemia cells.
AB  - Naturally occurring dietary compound resveratrol (RES), possessing
      chemopreventive and cytostatic properties, has been shown as potent sensitizer
      for apoptosis induced by a variety of anticancer drugs. Cell cycle analysis in
      sensitive promyelocytic leukemia HL60 cell line and its multidrug-resistant
      variant HL60/VCR (P-gp positive) treated with RES resulted in cell cycle arrest
      in S-phase in both cell variants. Flow cytometry measurements showed diverse
      activities of RES in combination with anticancer drugs doxorubicin (DOX),
      cycloheximide (CHX), busulfan (BUS), gemcitabine (GEM) and paclitaxel (PTX), in
      some cases resulting in apoptosis induction, preferentially at the expense of S
      phase. Thus, RES could become a candidate to enhance the efficacy of combination
      anticancer therapy in a variety of human cancer cells inclusive leukemias.

PMID- 17013533
TI  - Analysis of ERBB2 and TOP2A gene status using fluorescence in situ hybridization
      versus immunohistochemistry in localized breast cancer.
AB  - The aim of our study was to assess the ERBB2 and TOP2A gene status in breast
      carcinoma tissue using fluorescence in situ hybridization (FISH) and to compare
      their amplification with immunohistochemistry assay (IHC) of the ERBB2, resp.
      topoisomerase IIalpha proteins. TOP2A status is important in tailored treatment
      as topoisomerase IIalpha is the molecular target for topoisomerase IIalpha
      inhibitors. This study was conducted to determine whether the methods are
      equivalent in their assessment of TOP2A status and to correlate the genetic
      findings with basic tumor and disease characteristics. Locus specific ERBB2,
      TOP2A genes and chromosome 17 centromeres (CEP17) probes were hybridized to 72
      formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with non
      metastatic breast carcinoma (M0). The ERBB2, TOP2A and CEP17 signals were counted
      and gene numbers per nucleus or per CEP17 were calculated, respectively. Sections
      were also stained with commercial polyclonal antibody (HercepTestTM), anti
      topoisomerase IIalpha monoclonal antibody (clone SWT3D1) and scored for the
      presence of membrane/nuclear staining. ERBB2 amplification was found in 20.3%,
      ERBB2 and TOP2A co-amplification was detected in 14.5% of cases. Deletion of the
      ERBB2/TOP2A gene was found in 1.4/2.8% of sections, respectively. Concordance of
      FISH and IHC techniques in the evaluation of ERBB2 and TOP2A status was found in
      88.4% and 66.7%, respectively. The low concordance of FISH versus IHC in the
      evaluation of TOP2A status was mainly due to the presence of TOP2A amplified
      tumors in IHC negative or weakly positive specimens. Topoisomerase IIalpha
      expression was increased in bigger tumors, although direct correlation with tumor
      grading was not found. ERBB2 amplification was found in more aggressive breast
      cancers with grades 2 and 3, respectively. Interestingly, chromosome 17 polysomy
      was more frequently observed among older women (>55 years), suffering usually
      from less aggressive disease. Our results confirm the high concordance of the
      ERBB2 and TOP2A gene co-amplification in breast carcinoma. Differences between
      FISH and IHC in the case of ERBB2 gene status were found only in IHC 2+ sections
      as reported in the literature. However, our study points to the importance of
      FISH examination of TOP2A gene status in all tumors with ERBB2 amplification.

PMID- 17013534
TI  - Mung bean sprout (Phaseolus aureus) nuclease and its biological and antitumor
      effects.
AB  - Bovine seminal ribonuclease (BS RNase), a dimeric homolog of bovine pancreatic
      ribonuclease (RNase A), is known to display special biological activities namely
      cytotoxicity for human tumor cells. Because some plant ribonucleases have a
      similar mass weight and structure as the animal ribonuclease, effects of a
      commercial product of Mung bean (Phaseolus aureus) nuclease (PhA) were studied on
      proliferation of ML-2 human tumor cells, as well as it's aspermatogenic,
      embryotoxic, immunogenic, and immunosuppressive activity, and therapeutic
      efficiency in athymic mice bearing human melanoma tumor. Concerning the
      antiproliferative activity, PhA nuclease was almost non-effective in vitro on ML
      2 cells and also immunosuppressive activity on human lymphocyte in mixed culture
      was very low compared to that of BS RNase. However, significant antitumor
      activity was detected on human melanoma tumor after intratumoral or
      intraperitoneal administration into the mice. Furthermore conjugate of PhA
      nuclease with polyethylene glycol (PEG) injected seven times at the dose of 10
      microg intraperitoneally showed identical antitumor activity as that of bovine
      seminal ribonuclease (BS RNase) injected by the same way at ten times higher
      dose. Both PhA and BS RNases exerted strong aspermatogenic effect on the width of
      spermatogenic layers while RNase A administration at ten times higher
      concentration was ineffective. PhA nuclease when compared by means of antibody
      cross reaction with RNase A, BS RNase and wheat leaf neutral RNase (WLN-RNase)
      was found to be immunologically similar to RNase A and WLN-RNase, meanwhile BS
      RNase showed much higher antigenicity in comparison with them.

PMID- 17013535
TI  - Acute toxicity of conformal high dose interstitial brachytherapy boost in
      prostate cancer.
AB  - Over the past few years, brachytherapy has become more and more common in the
      treatment of prostate cancer, largely thanks to the reduced amount of acute and
      chronic side effects. At the same time, brachytherapy also allows dose
      escalation, resulting in significant improvements in the treatment results. From
      August 2004 to June 2005, we irradiated 40 patients suffering from T1c-T3a
      prostate cancer. All of the patients underwent external beam radiotherapy with a
      median dose of 45-50.4 Gy and a conformal high dose interstitial brachytherapy
      boost (two fractions, 8 Gy per fraction). The patients were divided into three
      groups: low risk of recurrence (11 patients - 27.5%), intermediate risk (14
      patients - 35%) and high risk (15 patients - 37.5%). The medium age of the
      patients was 68.7 years (between 55 and 77). Hormonal treatment was carried out
      17 patients (42.5%). We evaluated the quality of each implantation, including the
      maximum urethral and rectal dose. The calculated doses were compared with
      measurements by in vivo dosimetry. Acute toxicity was evaluated in all of the
      patients according to the Radiation Therapy Oncology Group (RTOG) scale. Each of
      the patients completed an International Prostatic Symptom Score (IPSS)
      questionnaire. Acute genitourinary morbidity grade 1 was recorded in 37.5% of
      patients; grade 2 in 15% of patients. Urine retention in one of the patients
      resulted in the need to perform an epicystostomy. According to the IPSS score,
      the majority of patients (90%) experienced an improvement in symptoms related to
      quality of life. Grade 1 acute gastrointestinal toxicity was recorded in 40% of
      the patients. Grades 2-4 were not recorded. Here, we show that the combination of
      external beam radiotherapy and high dose rate (HDR) brachytherapy in the
      treatment of early prostate cancer to be feasible and well tolerated. Acute
      toxicity was low and scarcely influenced the quality of life. Among the risk
      factors of genitourinary toxicity was the volume of the prostate. For
      gastrointestinal toxicity, risk factors included the combination of HDR
      brachytherapy and external beam radiotherapy to the pelvis, as well as hormonal
      treatment.

PMID- 17013536
TI  - In vivo fluorescence diagnostics and photodynamic therapy of gastrointestinal
      superficial polyps with aminolevulinic acid. A clinical and spectroscopic study.
AB  - In the present study initial results of clinical study related to the treatment
      of patients having different types of precancerous lesions in the area of
      esophagus, stomach and intestine by photodynamic therapy (PDT) based on
      aminolevulinic acid (ALA-PDT) are reported. The procedure was performed by laser
      fibre system with the light guides introduced through biopsy channel of an
      endoscope. In addition, in vivo fluorescent diagnostics and spectral analyses of
      biopsies were performed. Each patient had a positive response to therapy. In two
      cases there was a total response and in other five cases more than sixty percent
      of suspected area was removed. Additionally, sigilocellular carcinoma of stomach
      was revealed in one case. It appears from the results of this study, that the
      treatment of precancerous lesions with ALA-PDT could be successful treatment
      modality.

PMID- 17013537
TI  - Immunogold detection of CD3 and CD4 antigens in patients with Mycosis fungoides.
AB  - In this study, we analyzed the distribution of CD3 and CD4 antigens at the
      ultrastructural level in tissue samples from mycosis fungoides patients using
      double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens
      on the plasma membrane and intracellular. There were also clusters only of one
      type of the antigen and we could observe more often CD4 than CD3. Labeling of CD3
      and CD4 was not found in control cells incubated with non-immune serum. In
      conclusion, our ultrastructural studies not only visualized pattern distribution
      and relationship between CD3 and CD4 antigens but might also suggest that the
      type and form of distribution provides new clues to their possible translocation
      in mycosis fungoides cells.

PMID- 17013538
TI  - Anticancer effects of various Iranian native medicinal plants on human tumor cell
      lines.
AB  - In this study the antineoplastic activity of methanolic extracts of six medicinal
      plants that are native to Iran, including Galium mite, Ferulago angulata, Stachys
      obtusicrena, Cirsium bracteosum and Echinophora cinerea was investigated.
      Different tumor cell lines were exposed to the extracts and cytotoxic analysis
      using MTT colorimetric assay was performed. Quantification of percentage of cells
      undergoing apoptotic changes by flow cytometry, and DNA fragmentation analysis on
      sensitive cell lines was then carried out. Results obtained indicated that almost
      all of the extracts more or less had the capacity to decrease the proliferation
      of tumor cells. Among the plants, the highest activity against K562 leukemia cell
      line was found for E. cinerea and C. bracteosum with IC50 less than 20 microg/ml
      followed by G. mite with IC50 of 39.8 microg/ml. F. angulata and E. cinerea,
      mostly inhibited Jurkat cells proliferation (IC50 less than 8 microg/ml). Fifty
      percent inhibition of Fen bladder cell carcinoma due to exposure to F. angulata
      and E. cinerea was found at concentrations of nearly 180 microg/ml. A549, a lung
      carcinoma cell, was mostly affected by S. obtusicrena (IC50 more than 200
      microg/ml). In flow cytometry analysis, C. bracteosum, E. cinerea, F. angulata
      and S. obtusicrena extracts demonstrated no remarkable effects on the cell cycle
      profile of K562 and Jurkat cells. Moreover, in DNA fragmentation analysis of
      treated cells, no ladder formation was detected. In contrary, G. mite caused more
      than 40% apoptosis in the K562 and Jurkat cells. In DNA fragmentation analysis G.
      mite extract produced ladder formation in these cells. In conclusion, these
      results indicated that the extracts used in this study have anti tumor activity
      particularly against the leukemia cell lines and that apoptosis is the possible
      cause of cell death observed due to the extract of G. mite.

PMID- 17013539
TI  - Carboxymethyl chitin-glucan enriched diet exhibits protective effects against
      oxidative DNA damage induced in freshly isolated rat cells.
AB  - The connection between dietary intake of carboxymethyl chitin-glucan (CM-CG,
      approximately 200 mg/kg body weight, during 21 days) and the response of freshly
      isolated rat cells to genotoxic treatment with a combination of photosensitizer
      Methylene Blue and visible light (MB+VL) was evaluated in presented study. Blood
      lymphocytes, testicular cells, and hepatocytes were isolated from rats fed by a
      standard or CM-CG enriched diet and in ex vivo conditions challenged with
      oxidative agent. Induced DNA damage was assessed using a modified comet assay.
      When added to the diet, CM-CG itself did not induce any negative effect on the
      health condition of animals or on level of DNA breaks in rat cells. Moreover, the
      cells isolated from CM-CG fed animals were more resistant to oxidative stress
      induced by visible light-excited Methylene Blue. In conclusion, we have
      demonstrated that carboxymethyl chitin-glucan represents a natural fungal
      polysaccharide that is able to exert antimutagenic properties upon application in
      diet.

PMID- 17013541
TI  - Radioimmunoscintigraphy of colorectal carcinomas with three different
      radiopharmaceuticals.
AB  - The aim of the study was evaluation of the clinical reliability of the
      immunoscintigraphy for the detection of metastases and recurrences of colorectal
      carcinomas using three different radiopharmaceutical substances. With IMACIS 1,
      the number of true negative findings (TN) was 4/7 and true positive (TP) 3/7,
      while in one patient, the results of immunoscintigraphy significantly influenced
      the therapeutical management. With INDIMACIS 19-9, there were 2/8 TN and 6/8 TP.
      In three patients, immunoscintigraphy results influenced patient further
      management. With ONCOSCINT in 2 patients findings were TN, in one FN and in one
      FP. In 3 patients, immunoscintigraphy influenced the management of the patient.
      Other imaging methods (CT, US, MRI) have advantage in detection of liver
      metastases, while immunoscintigraphy is more specific for the assessment of
      reccurences of the abdominal tumors. Thus immunoscintigraphy should be applied in
      patients with suggested recurrences and inconclusive outcome of routine
      diagnostic workup.

PMID- 17013540
TI  - Loss of heterozygosity on chromosomes 2p, 3p, 18q21.3 and 11p15.5 as a poor
      prognostic factor in stage II and III (FIGO) cervical cancer treated by
      radiotherapy.
AB  - Loss of heterozygosity (LOH) has been shown to be an important prognostic factor
      in a variety of malignant neoplasm's. Cervical cancer develops as result of
      multiple genetic alterations. The aim of this study was to analyze presence of
      LOH in cervical cancer and to identify the correlation between LOH and survival
      and relapse-free survival time in patients treated with radiotherapy. Studies
      were performed on tumor specimens and venous blood from 20 patients with cervical
      cancer (squamous cell carcinoma G2 and G3) in stage II and III (FIGO) treated
      with radiotherapy. DNA was isolated using organic extraction. Additional
      microcolumn purification was performed. The fluorescent multiplex polymerase
      chain reaction (PCR) was used to amplify 10 microsatellite loci included in
      commercially available human identification kits. Microsatellite marker BAT 26
      was amplified in separate PCR reactions. 75% cervical cancers manifested LOH. LOH
      in BAT 26 analysis (chromosome 2) was present in all these specimens. 60% of the
      cases showed LOH at one or more of other examined loci (mostly on 3p, 18q21.3,
      and 11p15.5). Eight of nine cervical cancers in clinical stage III showed LOH.
      All cases of G3 squamous cell carcinoma of the cervix manifested LOH on 2p.
      Patients with LOH have worse prognosis for survival and relapse-free survival
      compared to patients without LOH.

PMID- 17013542
TI  - Concurrent chemoradiotherapy in patients with nasopharyngeal cancer: prognostic
      significance of low expression of bax.
AB  - A randomized trial has demonstrated that concurrent chemoradiotherapy (CRT) is
      superior to radiotherapy (RT) alone in locally advanced nasopharyngeal cancer
      (NPC). Our study comprise 35 patients with locally advanced NPC (stage I: 1, II:
      12, III: 7, IV: 15) with 1 cycle of induction chemotherapy (5-fluorouracil 1,000
      mg/m(2)/day and cisplatin 20 mg/m(2)/day, days 1- 4) followed by concurrent CRT
      starting on day 22. Concurrent CRT consisted of RT (70 Gy/35 fractions for 7
      weeks) with cisplatin 20 mg/m(2)/day for 4 days on weeks 1, 4, 7 of RT. Complete
      response (CR) was achieved in 33 patients (94%). Four-year progression-free
      survival (PFS) and overall survival (OS) of all patients were 57% and 65%,
      respectively. In analysis of prognostic factors, low expression of bax was the
      most significant independent predictor of poor prognosis in both PFS (p=0.002)
      and OS (p=0.008). In conclusion, the outcome of patients treated with this
      combined therapeutical modality appears to be comparable with that of Intergroup
      0099 trial with high CR rate. Low expression of bax was significantly associated
      with poor PFS and OS.

PMID- 17013543
TI  - Genetic analysis of a novel Alaska barley yellow dwarf virus in the family
      Luteoviridae.
AB  - A new plant virus belonging to the family Luteoviridae and isolated from diseased
      oat (Avena sativa L.) plants was discovered in Alaska in 2003. Even though plants
      with red/orange leaves were indicative of barley yellow dwarf disease, they were
      not reactive to specific antibodies corresponding to barley yellow dwarf virus
      (BYDV)-MAV, -PAV, -SGV, and cereal yellow dwarf virus-RPV from enzyme-linked
      immunosorbent assays (ELISA). An alternative RT-PCR assay that incorporated Shu
      F/Yan-R primers for detection of BYDV-MAV, -PAS, -PAV, and SGV was effective in
      producing approximately 830-nt fragments that contained genomic sequences to the
      3'-terminus of the polymerase gene (ORF 2), the intergenic region ( approximately
      113 nt), the coat protein gene (ORF 3), and the putative movement gene (ORF 4).
      The Alaskan isolates were most similar to BYDV-MAV with only about 77 and 80%
      amino acid identity in the CP and ORF 4, respectively. The Alaska isolates coat
      protein gene sequences differed in several regions that otherwise are conserved
      among BYDV-MAV isolates, and may be important in serological variations,
      accounting for the negative ELISA results. Based upon sequence and serological
      differences, we concluded that the Alaskan BYDV-MAV-like isolates formed a novel
      species tentatively in the genus Luteovirus, and propose the name BYDV-ORV (oat
      red-leaf virus).

PMID- 17013544
TI  - Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1
      (xGPAT1).
AB  - A novel murine glycerol-3-phosphate acyltransferase-like protein 1 (named xGPAT1)
      has been cloned. The mouse xGPAT1 gene is located on mouse Chromosome 2, spans
      >19 kb, and consists of at least 23 exons. The protein is 32% identical and 72%
      similar to mouse mitochondrial GPAT (mtGPAT) on the amino acid level. Sequencing
      analysis confirmed that xGPAT1 has a 2403-bp open reading frame (ORF) that
      encodes an 801-amino acid protein with an estimated molecular mass of 89.1 kDa. A
      hydropathy plot of the deduced xGPAT1 protein showed a high degree of similarity
      with that of the mtGPAT protein. Using 5'-rapid amplification of cDNA ends, two
      alternate, untranslated exon 1 (1a and b) isoforms were obtained, generating
      variants xGPAT1-v1 and xGPAT1-v2. xGPAT1-v1 is expressed in mouse heart, liver,
      spleen, kidney and murine inner medullary collecting duct 3 (mIMCD3) cells, while
      xGPAT1-v2 is expressed in mouse liver, spleen, kidney, white and brown adipose
      tissues and 3T3-L1 pre- and post-adipocytes. xGPAT1 was distributed in the
      membrane fraction and showed GPAT activity when epitope-tagged xGPAT1 was
      expressed in Chinese hamster ovary (CHO)-K1 cells.

PMID- 17013545
TI  - Acyl-CoA binding proteins; structural and functional conservation over 2000 MYA.
AB  - Besides serving as essential substrates for beta-oxidation and synthesis of
      triacylglycerols and more complex lipids like sphingolipids and sterol esters,
      long-chain fatty acyl-CoA esters are increasingly being recognized as important
      regulators of enzyme activities and gene transcription. Acyl-CoA binding protein,
      ACBP, has been proposed to play a pivotal role in the intracellular trafficking
      and utilization of long-chain fatty acyl-CoA esters. Depletion of acyl-CoA
      binding protein in yeast results in aberrant organelle morphology incl.
      fragmented vacuoles, multi-layered plasma membranes and accumulation of vesicles
      of variable sizes. In contrast to synthesis and turn-over of glycerolipids, the
      levels of very-long-chain fatty acids, long-chain bases and ceramide are severely
      affected by Acb1p depletion, suggesting that Acb1p, rather than playing a general
      role, serves specific roles in cellular lipid metabolism.

PMID- 17013546
TI  - Spiritual coping, family history, and perceived risk for breast cancer--can we
      make sense of it?
AB  - Differences in spiritual beliefs and practices could influence perceptions of the
      role of genetic risk factors on personal cancer risk. We explored spiritual
      coping and breast cancer risk perceptions among women with and without a reported
      family history of breast cancer. Analyses were conducted on data from 899 women
      in primary care clinics who did not have breast cancer. Structural equation
      modeling (SEM), linear, and logistic modeling tested an interaction of family
      history of breast cancer on the relationship between spiritual coping and risk
      perceptions. Overall analyses demonstrated an inverse relationship between
      spiritual coping and breast cancer risk perceptions and a modifying effect of
      family history. More frequent spiritual coping was associated with lower risk
      perceptions for women with positive family histories, but not for those with
      negative family histories. Results support further research in this area that
      could influence communication of risk information to cancer genetic counseling
      patients.

PMID- 17013548
TI  - Phylogenetic assignment and mechanism of action of a crop growth promoting
      Rhizobium radiobacter strain used as a biofertiliser on graminaceous crops in
      Russia.
AB  - The taxonomic position of "Agrobacterium radiobacter strain 204," used in Russia
      as a cereal crop growth promoting inoculant, was derived by a polyphasic
      approach. The phenotypic analyses gave very similar biochemical profiles for
      strain 204, Rhizobium radiobacter NCIMB 9042 (formerly the A. radiobacter type
      strain) and R. radiobacter NCIMB 13307 (formerly the Agrobacterium tumefaciens
      type strain). High percentage similarities, above the species separation level,
      were observed between the 16S rRNA, fusA and rpoB housekeeping gene sequences of
      these three strains, and the genomic DNA-DNA hybridisation of strain 204 against
      the type strain of R. radiobacter NCIMB 9042 was over 70%. Strain 204 is not
      phytopathogenic and it does not fix atmospheric N2 or form a physical association
      with the roots of barley. Strain 204 culture and culture supernatant stimulated
      the rate of mobilisation of seed reserves of barley in darkness and promoted its
      shoot growth in the light. Gibberellic acid (GA) concentration was 1.3 microM but
      indole acetic acid was undetectable (< 50 nM) in cultures of strain 204. It is
      concluded that strain 204 is phenotypically and genotypically very similar to the
      current R. radiobacter type strain and that the mechanism of its effect on growth
      of cereals is via the production of plant growth promoting substances. GA is
      likely to play an important role in the strain 204 stimulation of early growth of
      barley.

PMID- 17013549
TI  - Isolation of aminopeptidase N genes of food associated propionibacteria and
      observation of their transcription in skim milk and acid whey.
AB  - In this study consensus oligonucleotides PN5/PN3 were designed by aligning the
      aminopeptidase N genes (pepN) of various actinobacteria and applied to the
      isolation of the pepN genes of dairy propionibacteria (PAB) and closely related
      species associated with food. This allowed sequencing of a pepN gene region from
      Propionibacterium jensenii LMG 16541. The sequence of this gene was completed by
      inverse PCR. Consensus primer pairs NU1/D1 and NU2/D1 were derived from the
      alignment of the new sequence with its homologues in Propionibacterium acnes and
      other actinobacteria; these were used to start sequencing of the pepN genes of
      Propionibacterium freudenreichii, Propionibacterium thoenii, Propionibacterium
      microaerophilum, Propionibacterium acidipropionici, Propioni bacterium
      cyclohexanicum and Propionibacterium microaerophilum. Reverse transcription
      coupled with PN5/PN3 and NU1/D1 PCR tests indicated that the pepN genes of P.
      jensenii and P. freudenreichii are expressed during growth in skim milk and acid
      whey.

PMID- 17013550
TI  - Production, purification and partial characterisation of a novel laccase from the
      white-rot fungus Panus tigrinus CBS 577.79.
AB  - Extracellular laccase from Panus tigrinus CBS 577.79 was produced in a bubble
      column reactor using glucose-containing medium supplemented with 2,5-xylidine
      under conditions of nitrogen sufficiency. The main laccase isoenzyme was purified
      to apparent homogeneity by ultra-filtration, anion-exchange chromatography and
      gel filtration that led to a purified enzyme with a specific activity of 317 IU
      (mg protein)-1 and a final yield of 66%. Laccase was found to be a monomeric
      protein with a molecular mass of 69.1 kDa, pI of 3.15 and 6.9% N-glycosylation of
      the high mannose type. Temperature and pH optima were 55 degrees C and 3.75 (2,6
      dimethoxyphenol as substrate). At 50 and 60 degrees C, the enzyme half-lives were
      281 and 25 min, respectively. The P. tigrinus laccase oxidized a wide range of
      both naturally occurring and synthetic aromatic compounds: the highest catalytic
      efficiencies were for 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic) acid and
      2,6-dimethoxyphenol (5.99x10(6) and 3.07x10(6) M-1 s-1, respectively). Catalytic
      rate constants for typical N-OH redox mediators, such as 1-hydroxybenzotriazole
      (2.6 s-1), violuric acid (8.4 s-1) and 2,2,6,6-tetramethylpiperidin-N-oxide
      radical (7.8 s-1), were found to be higher than those reported for other high
      redox potential fungal laccases.

PMID- 17013551
TI  - Assessment of QT liabilities in drug development.
AB  - Since the publication, in 1997, of the CPMP (Committee for Proprietary Medicinal
      Products) Points to Consider document on "The assessment of potential for QT
      prolongation by non-cardiovascular medicinal products," both regulatory bodies
      and the pharmaceutical industry have paid increasing attention to the conduct of
      careful preclinical studies on the subject. Regulatory attention has focused on
      the drafting of Safety Pharmacology guidelines through the ICH (International
      Conference on Harmonization) process, which resulted in approval by the ICH and
      acceptance by the three main regions (USA, Europe, and Japan) of the ICH S7A
      guideline. The guideline does not deal only with cardiovascular studies and does
      not provide guidance on QT investigations. This part has been deferred to a
      second guideline (ICH S7B). Nevertheless, pharmaceutical companies have
      implemented screening strategies aimed at selecting compounds that do not present
      QT liabilities. These strategies can differ according to the pharmaceutical
      class, while experimental models differ according to the stage of development of
      the compound. Several in vitro models are employed in discovery (radioligand
      binding, high-throughput patch clamp, efflux, and fluorescence assays). These
      models, coupled with in silico methods, allow companies to screen a high number
      of compounds. Other in vitro models, applied later in the R&D process (action
      potential duration, APD, in Purkinje fibers or papillary muscle and the isolated
      heart) are useful in better describing the activity of compounds on cardiac ion
      channels. The most robust and accepted in vivo test is represented by telemetry
      studies in conscious non-rodents.

PMID- 17013552
TI  - A suggested classification guide for PACS client applications: the five degrees
      of thickness.
AB  - This article defines and describes the numerous types of "clients" for picture
      archiving and communication systems (PACS). A radiologist uses a client to view
      images stored in the system. Many PACS are available in the market, and each
      offers different methods by which a client can view images from the server. The
      terminology used to describe these different methods can cause confusion and lead
      to poor choice for those imaging team members who are given the task of
      purchasing, implementing, and supporting the PACS. We propose a classification of
      clients with respect to their impact on client work stations, an effect often
      referred to as the application's thickness. The thinner the client, the less
      effect it has on the hosting work station. In contrast, a thick client consumes
      the work station's resources and often prevents a work station from being used to
      effectively run anything other than the client application. Functionality and
      supportability are highlighted as key and interacting metrics in determining
      optimal correct PACS solutions. The importance of a clear understanding of the
      needs and requirements of all users as well as the client application is
      emphasized. This relationship between supportability and functionality becomes
      increasingly important as the industry shifts to enterprise information
      technology solutions.

PMID- 17013553
TI  - A targeted real-time PCR assay for studying naphthalene degradation in the
      environment.
AB  - A quantitative real-time polymerase chain reaction (PCR) assay was developed for
      monitoring naphthalene degradation during bioremediation processes. The
      phylogenetic affiliations of known naphthalene-hydroxylating dioxygenase genes
      were determined to target functionally related bacteria, and degenerate primers
      were designed on the basis of the close relationships among dioxygenase genes
      identified from naphthalene-degrading Proteobacteria. Evaluation of the
      amplification specificity demonstrated that the developed real-time PCR assay
      represents a rapid, precise means for the group-specific enumeration of
      naphthalene-degrading bacteria. According to validation with bacterial pure
      cultures, the assay discriminated between the targeted group of naphthalene
      dioxygenase sequences and genes in other naphthalene or aromatic hydrocarbon
      degrading bacterial strains. Specific amplification of gene fragments sharing a
      high sequence similarity with the genes included in the assay design was also
      observed in soil samples recovered from large-scale remediation processes. The
      target genes could be quantified reproducibly at over five orders of magnitude
      down to 3 x 10(2) gene copies. To investigate the suitability of the assay in
      monitoring naphthalene biodegradation, the assay was applied in enumerating the
      naphthalene dioxygenase genes in a soil slurry microcosm. The results were in
      good agreement with contaminant mineralization and dot blot quantification of
      nahAc gene copies. Furthermore, the real-time PCR assay was found to be more
      sensitive than hybridization-based analysis.

PMID- 17013554
TI  - Yeast diversity in the extreme acidic environments of the Iberian Pyrite Belt.
AB  - In the Iberian Pyrite Belt (IPB), acid rock drainage gives rise to aquatic
      habitats with low pH and high concentrations of heavy metals, a situation that
      causes important environmental problems. We investigated the occurrence and
      diversity of yeasts in two localities of the IPB: Sao Domingos (Portugal) and Rio
      Tinto (Spain). Yeast isolation was performed on conventional culture media (MYP),
      acidified (pH 3) media (MYP3), and on media prepared with water from the study
      sites (MYPw). The main goal of the study was to determine the structure of the
      yeast community; a combination of molecular methods was used for accurate species
      identifications. Our results showed that the largest fraction of the yeast
      community was recovered on MYPw rather than on MYP and MYP3. Twenty-seven yeast
      species were detected, 48% of which might represent undescribed taxa. Among
      these, an undescribed species of the genus Cryptococcus required low pH for
      growth, a property that has not been observed before in yeasts. The communities
      of S. Domingos and R. Tinto showed a considerable resemblance, and eight yeast
      species were simultaneously found in both localities. Taking into consideration
      the physicochemical parameters studied, we propose a hierarchic organization of
      the yeast community in terms of high-, intermediate-, or low-stress conditions of
      the environment. According to this ranking, the acidophile yeast Cryptococcus sp.
      5 is considered the most tolerant species, followed by Cryptococcus sp. 3 and
      Lecytophora sp. Species occurring in situations of intermediate environmental
      stress were Candida fluviatilis, Rhodosporidium toruloides, Williopsis
      californica, and three unidentified yeasts belonging to Rhodotorula and
      Cryptococcus.

PMID- 17013555
TI  - SET domain protein lysine methyltransferases: Structure, specificity and
      catalysis.
AB  - Site- and state-specific lysine methylation of histones is catalyzed by a family
      of proteins that contain the evolutionarily conserved SET domain and plays a
      fundamental role in epigenetic regulation of gene activation and silencing in all
      eukaryotes. The recently determined three-dimensional structures of the SET
      domains from chromosomal proteins reveal that the core SET domain structure
      contains a two-domain architecture, consisting of a conserved anti-parallel beta
      barrel and a structurally variable insert that surround a unusual knot-like
      structure that comprises the enzyme active site. These structures of the SET
      domains, either in the free state or when bound to cofactor S-adenosyl-L
      homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate
      complex, further yield the structural insights into the molecular basis of the
      substrate specificity, methylation multiplicity and the catalytic mechanism of
      histone lysine methylation.

PMID- 17013556
TI  - Structural genomics for membrane proteins.
AB  - Structure-based drug discovery has proven useful in improving and shortening the
      drug development process. The approach of structural genomics to study a large
      number of targets in parallel has been commonly applied to protein families and
      even whole genomes. Paradoxically, although membrane proteins represent the
      largest type of drug targets, up to 70% today, determination of their structure
      has been modest compared to that of soluble proteins. Because membrane proteins
      are important for drug discovery an emphasis has been placed on developing
      technologies and methods to determine membrane protein structures. Several
      structural genomics initiatives have been established, focusing on the structural
      biology of membrane proteins.

PMID- 17013557
TI  - Emery-Dreifuss muscular dystrophy at the nuclear envelope: 10 years on.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular degenerative
      condition with an associated dilated cardiomyopathy and cardiac conduction
      defect. It can be inherited in either an X-linked or autosomal manner by
      mutations in the nuclear proteins emerin and lamin A/C, respectively.
      Traditionally muscular dystrophies were associated with defects in sarcolemma
      associated proteins and, therefore, a nuclear connection suggested the existence
      of novel signalling pathways associated with this group of diseases.
      Subsequently, other mutations in the lamin A/C gene were attributed to a range of
      tissue-specific degenerative conditions, collectively known as the
      'laminopathies'. Therefore, any proposed hypothesis underlying the molecular
      mechanism of EDMD needs to include this anomaly. As we celebrate the 10th
      anniversary of the identification of emerin as a component of the nuclear
      envelope, I discuss here the available evidence that currently implicates EDMD as
      arising from perturbations in myogenic regulatory pathways, causing temporal
      delays in both cell cycle progression and muscle regeneration.

PMID- 17013558
TI  - Starch-binding domains in the post-genome era.
AB  - Starch belongs to the most abundant biopolymers on Earth. As a source of energy,
      starch is degraded by a large number of various amylolytic enzymes. However, only
      about 10% of them are capable of binding and degrading raw starch. These enzymes
      usually possess a distinct sequence-structural module, the so-called
      starchbinding domain (SBD). In general, all carbohydrate-binding modules (CBMs)
      have been classified into the CBM families. In this sequence-based classification
      the individual types of SBDs have been placed into seven CBM families: CBM20,
      CBM21, CBM25, CBM26, CBM34, CBM41 and CBM45. The family CBM20, known also as a
      classical C-terminal SBD of microbial amylases, is the most thoroughly studied.
      The three-dimensional structures have already been determined by X-ray
      crystallography or nuclear magnetic resonance for SBDs from five CBM families
      (20, 25, 26, 34 and 41), and the structure of the CBM21 has been modelled.
      Despite differences among the amino acid sequences, the fold of a distorted beta
      barrel seems to be conserved together with a similar way of substrate binding
      (mainly stacking interactions between aromatic residues and glucose rings). SBDs
      have recently been discovered in many non-amylolytic proteins. These may, for
      example, have regulatory functions in starch metabolism in plants or glycogen
      metabolism in mammals. SBDs have also found practical uses.

PMID- 17013559
TI  - TGF-beta transcriptionally activates the gene encoding the high-affinity
      adenosine transporter CNT2 in rat liver parenchymal cells.
AB  - The nucleoside transporter CNT2 is the highest-affinity adenosine transporter
      identified so far. Recent evidence suggests that CNT2 has functions other than
      salvage (i.e. modulation of purinergic responses). Here we identified TGF-beta1
      as a potent inducer of CNT2 protein expression in liver parenchymal cells. By
      contrast, CNT1, which is a target of multifunctional cytokines involved in liver
      cell proliferation, does not respond to TGF-beta1 treatment. Cloning of a murine
      CNT2 gene sequence with promoter-like activity enabled us to demonstrate that
      this cytokine exerts this effect by transcriptionally activating the CNT2
      encoding gene in a JNK-dependent manner. The evidence that CNT2 is not a target
      of multifunctional cytokines involved in hepatocyte proliferation, but instead,
      of a cytokine that plays major roles in differentiation and apoptosis, further
      supports the view that the main physiological role of this transporter protein is
      not nucleoside salvage.

PMID- 17013560
TI  - Toxicity of statins on rat skeletal muscle mitochondria.
AB  - We investigated mitochondrial toxicity of four lipophilic stains (cerivastatin,
      fluvastatin, atorvastatin, simvastatin) and one hydrophilic statin (pravastatin).
      In L6 cells (rat skeletal muscle cell line), the four lipophilic statins (100
      micromol/l) induced death in 27-49% of the cells. Pravastatin was not toxic up to
      1 mmol/l. Cerivastatin, fluvastatin and atorvastatin (100 micromol/l) decreased
      the mitochondrial membrane potential by 49-65%, whereas simvastatin and
      pravastatin were less toxic. In isolated rat skeletal muscle mitochondria, all
      statins, except pravastatin, decreased glutamate-driven state 3 respiration and
      respiratory control ratio. Beta-oxidation was decreased by 88-96% in the presence
      of 100 micromol/l of the lipophilic statins, but only at higher concentrations by
      pravastatin. Mitochondrial swelling, cytochrome c release and DNA fragmentation
      was induced in L6 cells by the four lipophilic statins, but not by pravastatin.
      Lipophilic statins impair the function of skeletal muscle mitochondria, whereas
      the hydrophilic pravastatin is significantly less toxic.

PMID- 17013561
TI  - Bacterial resuscitation factors: revival of viable but non-culturable bacteria.

PMID- 17013562
TI  - Melanoma cells exhibit strong intracellular TASK-3-specific immunopositivity in
      both tissue sections and cell culture.
AB  - Amplification of the kcnk9 gene and overexpression of the encoded channel protein
      (TASK-3) seems to be involved in carcinogenesis. In the present work, TASK-3
      expression of melanoma cells has been studied. For the investigation of TASK-3
      specific immunolabelling, a monoclonal antibody has been developed and applied
      along with two, commercially available polyclonal antibodies targeting different
      epitopes of the channel protein. Both primary and metastatic melanoma cells
      proved to be TASK-3 positive, showing prominent intracellular TASK-3-specific
      labelling; mostly concentrating around or in the proximity of the nuclei. The
      immunoreaction was associated with the nuclear envelope, and with the processes
      of the cells and it was also present in the cell surface membrane. Specificity of
      the immunolabelling was confirmed by Western blot and transfection experiments.
      As TASK-3 immunopositivity of benign melanocytes could also be demonstrated, the
      presence or absence of TASK-3 channels cannot differentiate between malignant and
      non-malignant melanocytic tumours.

PMID- 17013563
TI  - Unscheduled CDK1 activity in G1 phase of the cell cycle triggers apoptosis in X
      irradiated lymphocytic leukemia cells.
AB  - Cyclin-dependent kinase 1 (CDK1) is a major component of the cell cycle
      progression engine. Recently, several investigations provided evidence
      demonstrating that unscheduled CDK1 activation may also be involved in apoptosis
      in cancerous cells. In this article, we demonstrate that X-ray irradiation
      induced G1 arrest in MOLT-4 lymphocytic leukemia cells, the arrest being
      accompanied by reduction in the activity of CDK2, but increased CDK1 activity and
      cell apoptosis in the G1 phase. Interestingly, this increase in CDK1 and
      apoptosis by ionizing radiation was prevented by pretreatment with the CDK1
      inhibitor, roscovitine, suggesting that CDK1 kinase activity is required for
      radiation-induced apoptotic cell death in this model system. Furthermore, cyclin
      B1 and CDK1 were detected co-localizing and associating in G1 phase MOLT-4 cells,
      with the cellular lysates from these cells revealing a genotoxic stress-induced
      increase in CDK1 phosphorylation (Thr-161) and dephosphorylation (Tyr-15), as
      analyzed by postsorting immunoprecipitation and immunoblotting. Finally, X
      irradiation was found to increase Bcl-2 phosphorylation in G1 phase cells. Taken
      together, these novel findings suggest that CDK1 is activated by unscheduled
      accumulation of cyclin B1 in G1 phase cells exposed to X-ray, and that CDK1
      activation, at the wrong time and in the wrong phase, may directly or indirectly
      trigger a Bcl-2-dependent signaling pathway leading to apoptotic cell death in
      MOLT-4 cells.

PMID- 17013564
TI  - The E-site story: the importance of maintaining two tRNAs on the ribosome during
      protein synthesis.
AB  - In the sixties James Watson suggested a twosite model for the ribosome comprising
      the P site for the peptidyl transfer RNA (tRNA) before peptide-bond formation and
      the A site, where decoding takes place according to the codon exposed there. In
      the eighties a third tRNA binding site was detected, the E site, which was
      specific for deacylated tRNA and turned out to be a universal feature of
      ribosomes. However, despite having three tRNA binding sites, only two tRNAs
      occupy the ribosome at a time during protein synthesis: at the A and P sites
      before translocation (PRE state) and at the P and E sites after translocation
      (POST state). The importance of having two tRNAs in the POST state has been
      revealed during the last 25 years, showing that the E site contributes two
      fundamental features: (i) the fact that incorporation of a wrong amino acid is
      not harmful for the cell (only 1 in about 400 misincorporations destroys the
      function of a protein) stems from the presence of an E-tRNA; (ii) maintenance of
      the reading frame is one of the most remarkable achievements of the ribosome,
      essential for faithful translation of the genetic information. The presence of
      the POST state E-tRNA prevents loss of the reading frame.

PMID- 17013565
TI  - Spatiotemporal asymmetric auxin distribution: a means to coordinate plant
      development.
AB  - The plant hormone auxin plays crucial roles in regulating plant growth
      development, including embryo and root patterning, organ formation, vascular
      tissue differentiation and growth responses to environmental stimuli. Asymmetric
      auxin distribution patterns have been observed within tissues, and these so
      called auxin gradients change dynamically during different developmental
      processes. Most auxin is synthesized in the shoot and distributed directionally
      throughout the plant. This polar auxin transport is mediated by auxin influx and
      efflux facilitators, whose subcellular polar localizations guide the direction of
      auxin flow. The polar localization of PIN auxin efflux carriers changes in
      response to developmental and external cues in order to channel auxin flow in a
      regulated manner for organized growth. Auxin itself modulates the expression and
      subcellular localization of PIN proteins, contributing to a complex pattern of
      feedback regulation. Here we review the available information mainly from studies
      of a model plant, Arabidopsis thaliana, on the generation of auxin gradients, the
      regulation of polar auxin transport and further downstream cellular events.

PMID- 17013566
TI  - Role of transforming growth factor-beta in the progression of heart failure.
AB  - Transforming growth factor (TGF-beta) is a multifunctional peptide growth factor
      that has an important role in the regulation of cell growth, differentiation, and
      repair in a variety of tissues. In mammals, the cytokine has three isoforms, TGF
      beta1, TGF-beta2, and TGF-beta3. TGF- beta1 is up-regulated by Ang II and
      induction of TGF-beta1 causes cardiac fibrosis. The stimulus that triggers the
      expression of TGF-beta1 may be repeated causing continual injury, which is
      associated with an increase in the activity of Ang II in heart tissue. The
      interplay between Ang II and TGF-beta1 causes continued activation that may
      result in chronic hypertension and progressive myocardial fibrosis, leading to
      heart failure. The regulation of TGF-beta1 secretion and action involves complex
      transcriptional events. Overproduction of TGF-beta1 underlies tissue fibrosis.
      Understanding the actions and signaling transduction of TGF-beta could lead to
      the development of therapeutic options that may be effective in inhibiting
      myocardial fibrosis triggered by TGF-beta1 in heart failure.

PMID- 17013568
TI  - How to reduce stress and anxiety in patients undergoing cardiac catheterization?

PMID- 17013567
TI  - Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal
      impairment.
AB  - INTRODUCTION: The prevalence of both osteoporosis and renal impairment increases
      with age. METHODS: Using data from the Fracture Prevention Trial, the safety and
      efficacy of teriparatide [rhPTH(1-34)] in postmenopausal women with osteoporosis
      and renal impairment were explored. Patients were required to have serum
      creatinine concentrations < or =2.0 mg/dl and normal serum parathyroid hormone
      (PTH) concentrations and were randomized to receive daily subcutaneous injections
      of placebo or teriparatide 20 or 40 mcg/day. Glomerular filtration rate (GFR) was
      estimated using the Cockcroft-Gault equation. Patients were defined from baseline
      assessments to have normal (GFR > or =80 ml/min), mildly impaired (GFR 50-79
      ml/min), or moderately impaired (GFR 30-49 ml/min) renal function for bone
      mineral density (BMD) and amino-terminal extension peptide of procollagen type 1
      (PINP) analyses, and normal (GFR > or =80 ml/min) or impaired (GFR <80 ml/min)
      renal function for fracture analyses. RESULTS AND CONCLUSIONS: Compared with
      patients with normal renal function, patients with renal impairment were older,
      shorter, weighed less, had been postmenopausal longer, and had lower baseline
      lumbar spine and femoral neck BMD. Compared with placebo, teriparatide
      significantly increased PINP and lumbar spine and femoral neck BMD within each
      renal function subgroup, and there was no evidence that these increases were
      altered by renal insufficiency (each treatment-by-subgroup interaction p>0.05).
      Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk
      reductions were similar and did not differ significantly between patients with
      normal or impaired renal function (treatment-by-subgroup interactions p>0.05).
      The incidences of treatment-emergent and renal-related adverse events were
      consistent across treatment assignment in the normal, mildly impaired, and
      moderately impaired renal function subgroups. Teriparatide induced changes in
      mean GFR were unaffected by baseline renal function (treatment-by-renal function
      interaction p>0.05 for normal, mildly impaired, or moderately impaired
      subgroups). Patients in all renal function categories treated with teriparatide
      20 or 40 mcg had an increased incidence of 4-6-h postdose serum calcium >10.6
      mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20
      mcg/day was not associated with significantly increased incidence of 4-6-h
      postdose serum calcium >11 mg/dl in any renal function category. Teriparatide
      therapy was associated with increased incidence of elevated uric acid, with the
      incidences being highest in patients with moderately impaired renal function and
      in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not
      suggest an increased incidence of gout or arthralgia or of nephrolithiasis events
      in teriparatide-treated patients with normal, mild, or moderate renal impairment.

PMID- 17013569
TI  - Amelioration of early radiation effects in oral mucosa (mouse) by intravenous or
      subcutaneous administration of amifostine.
AB  - PURPOSE: To quantify the reduction of radiation-induced oral mucositis by
      amifostine as a function of administration route. MATERIAL AND METHODS: Mucosal
      ulceration of lower mouse tongue epithelium was analyzed. Amifostine was injected
      at 1.8 mg/injection subcutaneously (s.c.) or intravenously (i.v.), 45 min or 10
      min prior to irradiation. With single-dose irradiation, a single amifostine
      injection was given. During daily fractionated irradiation (5 x 3 Gy) for 1 week,
      amifostine was administered s.c. or i.v. twice (days 0, 3), or s.c. on all
      irradiation days (days 0-4). With ten fractions over 2 weeks, five s.c.
      injections were given in week 1 (days 0-4) or week 2 (days 7-11), or both. Two
      i.v. injections were given either in week 1 (days 0, 3) or week 2 (days 7, 10).
      All fractionation protocols were terminated by graded test doses to generate full
      dose-effect curves. RESULTS: In a single-dose control experiment, the ED(50)
      (dose after which ulcer induction is expected in 50% of the mice) was 11.7 +/-
      1.4 Gy. Intravenous application of amifostine increased the ED(50) to 14.0 +/-
      1.4 Gy (p = 0.024), while s.c. administration had no significant effect. The
      ED(50) for test irradiation after 5 x 3 Gy was 5.8 +/- 1.4 Gy. Two s.c. or i.v.
      amifostine injections yielded ED(50) values of 7.2 +/- 1.1 Gy (p = 0.0984) or 7.6
      +/- 1.2 Gy (p = 0.0334); five s.c. injections increased the ED(50) to 8.2 +/- 0.9
      Gy (p = 0.0039). The ED(50) after 10 x 3 Gy/2 weeks was 6.6 +/- 1.8 Gy.
      Subcutaneous or intravenous administration of amifostine in week 1 yielded a
      significant increase in ED(50) to 9.4 +/- 2.5 Gy (p = 0.0099) and 10.0 +/- 2.2 Gy
      (p = 0.0014). By contrast, amifostine administration in week 2 had no significant
      effect. Administration in weeks 1 and 2 resulted in an ED(50) of 10.8 +/- 3.6 Gy
      (p = 0.0053). CONCLUSION: Amifostine during daily fractionated irradiation is
      effective only if administered in the initial treatment phase, i.e., week 1 in
      the mouse. The differences in the effect in weeks 1 and 2 suggest mechanisms of
      action other than radical scavenging.

PMID- 17013570
TI  - Quality assurance in the EORTC randomized trial 22922/10925 investigating the
      role of irradiation of the internal mammary and medial supraclavicular lymph node
      chain works.
AB  - BACKGROUND AND PURPOSE: A quality assurance (QA) program in conjunction with the
      EORTC trial investigating the role of adjuvant internal mammary and medial
      supraclavicular irradiation in stage I-III breast cancer is presented. The
      results of a dummy run procedure and of an individual case review are compared to
      each other. The effects of recommendations based on QA procedures on the protocol
      compliance are evaluated. MATERIAL AND METHODS: Prior to protocol activation all
      participating institutes were asked to produce treatment plans according to the
      guidelines of the protocol based on manual outlines of an average patient.
      Thereafter, they were asked to provide data on each of their first six randomized
      patients. RESULTS: The dummy run provided a lot of information on specific
      treatment techniques. In the individual case review, additional patient- and
      tumor-related data were collected, showing the use of anatomic information for
      treatment planning. A comparison between both procedures revealed that the
      individual case reports concurred more accurately with protocol guidelines than
      the dummy run. CONCLUSION: It was observed that the number of systematic protocol
      deviations was substantially decreased in trial patients compared to the dummy
      run case. Therefore, it is concluded that this extensive QA program had a
      positive effect on the consistency of all institutes participating in the trial.

PMID- 17013571
TI  - Postoperative irradiation in breast cancer patients with one to three positive
      axillary lymph nodes. Is there an impact of axillary extranodal tumor extension
      on locoregional and distant control?
AB  - BACKGROUND AND PURPOSE: To evaluate the impact of extracapsular extension (ECE)
      on locoregional and distant control in breast cancer patients with one to three
      positive axillary lymph nodes treated with postoperative irradiation. As shown in
      literature, ECE is diagnosed in up to 30% of node-positive breast cancer
      patients. Consequences of ECE and prognosis of these patients are unclear.
      PATIENTS AND METHODS: The medical records of 1,142 node-positive females with a
      carcinoma of the breast, postoperatively irradiated between 1994 and 2003, were
      retrospectively reviewed. Of the 274 patients presenting with one to three
      positive axillary lymph nodes, 91 (33.2%) showed ECE. While all patients were
      irradiated using tangential fields, only eight out of 274 patients received
      additional nodal irradiation. RESULTS: Patients' mean age was 58.2 years (range,
      28-96 years), and the mean observation period 42.9 months (range, 6.6-101
      months). In 93.4% of patients, locoregional control was achieved. On multivariate
      analysis of metastases-free survival, the hazard ratios for ECE and histological
      grade 3 were 2.71 (95% confidence interval [CI], 1.316-5.581; p = 0.007) and
      2.435 (95% CI, 1.008-5.885; p = 0.048), respectively. The 3-year and 5-year
      metastases-free survival rates for patients with ECE were 78% and 66%, compared
      to 90% and 87% in patients without ECE (p = 0.0048). CONCLUSION: Locoregional
      recurrence remains low in breast cancer patients (one to three positive axillary
      lymph nodes +/- ECE) treated with surgery, adequate axillary dissection, and
      tangential field irradiation only. However, ECE is significantly linked to a
      considerable risk for subsequent distant failure.

PMID- 17013572
TI  - Full-dose intraoperative radiotherapy with electrons in breast cancer. First
      report on late toxicity and cosmetic results from a single-institution
      experience.
AB  - PURPOSE: To investigate the feasibility of applying exclusive intraoperative
      radiation therapy (IORT) after conservative surgery in limited-stage breast
      carcinoma and to evaluate late effects and cosmetic results after this new
      conservative treatment. PATIENTS AND METHODS: From October 2000 to November 2002,
      47 consecutive patients with unifocal breast carcinoma up to a diameter of 2 cm
      received conservative surgery followed by IORT with electrons as the sole
      adjuvant local therapy. Three different dose levels were used: 20 Gy (seven
      patients), 22 Gy (20 patients), and 24 Gy (20 patients). Patients were evaluated
      using RTOG/EORTC scale to assess the incidence of late complications. During
      follow-up, a radiologic assessment with mammography and sonography was
      periodically performed and any breast-imaging alterations were reported. RESULTS:
      After a follow-up ranging from 36 to 63 months (median, 48 months), 15 patients
      developed breast fibrosis (grade 2 in 14 patients, grade 3 in one patient), two
      patients presented with grade 3 skin changes, one patient developed a clinically
      relevant fat necrosis, and one patient showed breast edema and pain. Two patients
      developed contralateral breast cancer and one distant metastases; no local
      relapses occurred. Asymptomatic findings of fat necrosis were observed at
      mammography in twelve patients (25.5%), while an hypoechoic area was revealed by
      sonography in ten patients (21.5%). In four patients (8%), mammographic and
      sonographic findings suggested malignant lesions and required a rebiopsy to
      confirm the benign nature of the lesion. CONCLUSION: IORT in breast carcinoma is
      still an experimental treatment option for select patients with breast cancer and
      its application should be restricted to prospective trials. Although preliminary
      data on local control are encouraging, a longer follow-up is needed to confirm
      the efficacy of IORT in breast cancer and to exclude that severe late
      complications compromise the cosmetic results or modify the radiologic breast
      appearance during follow-up increasing the need for additional investigations.

PMID- 17013573
TI  - Concurrent radiotherapy and taxane chemotherapy in patients with locoregional
      recurrence of breast cancer. A retrospective analysis.
AB  - BACKGROUND AND PURPOSE: Locoregional breast cancer recurrence is characterized by
      a high rate of systemic and local re-recurrence. Data on concurrent
      radiochemotherapy (RCT) in these cases are scarce. The purpose of this study was
      to evaluate feasibility, toxicity and efficacy of local control of a radiotherapy
      combined with a chemotherapy containing a taxane. PATIENTS AND METHODS: Between
      May 1999 and November 2004, 36 women referred to the authors' clinic because of
      locoregional breast cancer recurrence that was either inoperable (n = 29) or
      resected (n = 7) received concurrent irradiation and taxane monotherapy weekly
      (TAX/RT; n = 28: paclitaxel 90 mg/m(2), n = 24, or docetaxel 35 mg/m(2), n = 4)
      or taxane + cisplatin therapy (TAX/CIS/RT; n = 8; paclitaxel 135 mg/m(2) d1 and
      cisplatin 20 mg/m(2) d1-5 q28). RESULTS: Comparing TAX/RT with TAX/CIS/RT, the
      complete remission rate in patients with macroscopic tumor prior to RCT was
      significantly higher for TAX/RT than for TAX/CIS/RT (7/19 vs. 0/8; p = 0.046),
      but overall remission rates were comparable, i.e., partial remission: 11/20
      versus 6/8 cases, stable disease (no change): 1/20 versus 2/8 cases, and response
      rate: 95% versus 75%, respectively. The cumulative local recurrence-free survival
      rate at 1 and 2 years post-treatment was 83% and 68% and that of systemic
      recurrence-free survival 56% and 29%, respectively. The main toxic reactions of
      third-degree and higher were dermatitis in TAX/RT (57% vs. 11% for TAX/CIS/RT)
      and leukocytopenia in TAX/CIS/RT (62% vs. 7% for TAX/RT). CONCLUSION: Concurrent
      irradiation and taxane chemotherapy weekly, in particular with paclitaxel, is
      recommended due to response and acceptable side effects for treatment of
      inoperable locoregional breast cancer recurrence.

PMID- 17013574
TI  - Contrast-enhanced color duplex sonography (CDS): an alternative for the
      evaluation of therapy-relevant tumor oxygenation?
AB  - PURPOSE: To evaluate the predictive value of radiotherapeutically relevant tumor
      hypoxia by contrast-enhanced color duplex sonography (CDS). The objectification
      was based on pO(2) histography. MATERIAL AND METHODS: 25 patients with metastatic
      neck lymph node from a primary squamous carcinoma of the head and neck were
      examined. To visualize as many vessels as possible, a contrast enhancer
      (Levovist), Schering Corp., Germany) was administered. Horizontal and
      longitudinal sonographic scans with a thickness of 5 mm were performed on the
      metastatic neck lymph node. Color pixel density (CPD) was defined as the ratio of
      colored to gray pixels in a region of interest. It represents the extent of
      vascularization in the investigated slice. To assess the biological and clinical
      relevance of oxygenation measurement, the relative frequency of pO(2) readings <
      or = 2.5, 5.0, and 10.0 mmHg, as well as mean and median pO(2), were documented.
      RESULTS: In order to investigate the degree of linear association, the Pearson
      correlation coefficient was calculated. Moderate (/r/ > 0.5) to high (/r/ > 0.7)
      correlation was found between the CPD and the parameters of hypoxic fraction
      (pO(2) readings with values < or = 5.0 and 10.0 mmHg, as well as mean and
      median). There was only a slight correlation between CPD and the fraction of
      pO(2) values < or = 2.5 mmHg (r = -0.479). CONCLUSION: CPD represents the mean
      degree of vascularization. As a noninvasive measurement, this method seems
      feasible for evaluating the state of global oxygenation in superficial tumors.
      Nevertheless, this method is limited through its deficiency in describing the
      vascular heterogeneity of tumors.

PMID- 17013575
TI  - Potential time benefit in the assessment of recurrent rat rhabdomyosarcoma using
      positron emission tomography (PET) with (18)fluorodeoxyglucose depends on therapy
      specific growth delay.
AB  - PURPOSE: To correlate the potential time benefit of (18)F-fluorodeoxyglucose
      positron emission tomography ((18)FDG-PET) in terms of early detection of
      recurrences of subcutaneously growing R1H tumors with therapy-specific parameters
      of recurrent tumor. MATERIAL AND METHODS: Twelve, eleven, and seven recurrences
      were followed after fractionated radiotherapy, surgery, and chemotherapy for 6
      months, respectively, and (18)FDG-PET was performed weekly using a conventional
      full-ring whole-body PET scanner. By comparing PET results and actual tumor
      volume, the time benefit of (18)FDG-PET in detection of recurrent tumors of 0.1,
      0.2, and 0.5 cm(3) was determined for the different treatment strategies.
      RESULTS: A significant time benefit of (18)FDG-PET of 26.9 days and 67 days was
      solely determined for recurrences after radiotherapy of 0.2 cm(3) and 0.5 cm(3),
      respectively. The potential time benefit showed a strong correlation with growth
      delay, which was increased after radiotherapy due to a pronounced tumor-bed
      effect. CONCLUSION: The potential time benefit of (18)FDG-PET is strongly
      determined by the growth kinetics of the recurrence. A tumor-bed effect, which is
      a phenomenon solely seen after radiotherapy, favors early detection by (18)FDG
      PET. The experimental data, clinical experience and theoretical consideration all
      indicate a noticeable benefit of (18)FDG-PET especially after radiotherapeutic
      treatment.

PMID- 17013576
TI  - Laparoscopic seminal vesicle and pelvic lymph node resection before high-dose
      three-dimensional conformal radiation therapy for localized prostate cancer.
      Results of a dosimetric study.
AB  - PURPOSE: To analyze the dosimetric implications of seminal vesicle (SV) resection
      at the time of laparoscopic pelvic lymph node (PLN) dissection in patients
      presenting with high-risk prostate cancer regarding PLN and SV involvement.
      PATIENTS AND METHODS: Between June and September 2005, twelve patients underwent
      laparoscopic SV resection and PLN dissection before delivering a total dose of 80
      Gy through a three-dimensional conformal radiation therapy (3D-CRT). Dose-volume
      histograms (DVHs; rectum, bladder, femoral heads) were obtained from G1 (group 1
      with SV) and G2 (group 2 without SV) according to either three- dimensional or
      intensity-modulated treatment planning. All DVH medians were compared using the
      nonparametric sign test. RESULTS: SV resection during laparoscopic PLN dissection
      was performed in all twelve patients without major complications. DVH obtained
      with three-dimensional and intensity-modulated treatment planning showed that the
      median doses of RV(25%) (25% of rectal volume), RV(50%), RFHV(5%) (5% of right
      femoral head volume) and LFHV(5%) (5% of left femoral head volume) in G1 were
      significantly higher compared to those obtained in G2. CONCLUSION: For patients
      presenting with high-risk prostate cancer, SV resection performed at the time of
      laparoscopic PLN dissection allows to significantly decrease the dose delivered
      to the rectum, using either three-dimensional or intensity-modulated treatment
      planning, and to reduce the risk of acute and late rectal toxicity.

PMID- 17013578
TI  - [Cardiovascular secondary prevention].
AB  - Cardiovascular secondary prevention plays a fundamental role due to the rising
      average age of the population. The reorganization of the health care system is
      also becoming more important. Especially the needs of high-risk patients have to
      be prioritized. A change of habits (e. g. abnegation of nicotine, change in
      eating habits, obtaining a BMI<25) is the basis of preventive measures in order
      to maximize the effectivity of drug therapy. Here the application of statins
      takes center stage (if there are no contraindications) which minimizes the risk
      of coronary incidences by 30%. In case of high lipid blood level, fibrates have
      to be applied at a low level of HDL-cholesterol and omega-3 fatty acids at high
      values of triglycerides. Omega-3 fatty acids must be given in the form of 1 g
      ethyl esters of EPA and DHA, otherwise a significant reduction of fatal
      cardiovascular incidences cannot be proven. Recently ACE inhibitors have gained
      in importance because of their ability to reduce the formation of plaques.
      Furthermore beta-blockers and aspirin can be applied for therapeutic measures,
      whereas different periods of treatment are recommended by the guidelines. With
      the aid of algorithms it is possible to specify the risk of experiencing a second
      myocardial infarction.

PMID- 17013579
TI  - [Omega-3 fatty acids in secondary prevention after myocardial infarct].
AB  - The ESC (European Society of Cardiology) recommends treatment with highly
      concentrated omega-3 fatty acids after myocardial infarction. By daily
      application of 1 g 84% EPA/DHA-ethyl ester the mortality rate is significantly
      reduced as shown in the GISSI-Prevenzione study. The main reason for this
      protective effect is the serum concentration of EPA/DHA which can be adjusted by
      this dosage. On account of this fact the number of fatal arrhythmias decreases.
      Concerning secondary prevention omega-3 fatty acids must be given in this form
      continuously, otherwise a clinically effective level of fatty acids cannot be
      achieved. Therefore the application of EPA/DHA-ethyl esters should be preferred,
      because in this case the serum's level can be kept on a sufficiently high level
      as a result of their more prolonged release.

PMID- 17013580
TI  - [Lipometabolic disorder--cholesterol and triglycerides].
AB  - Resorption inhibitors for cholesterol are commonly applied today in case of
      hypercholesterolemia in addition to statins. This combination therapy reduces the
      value of the LDL concentration by 50-60%. A target value of 100 mg/dl should be
      adjusted in case of high-risk patients in order to also decrease coronary risk.
      The significance of the triglycerides level is also becoming increasingly
      important, for it describes a high cardiovascular risk due to an increase of
      adiposity and diabetes. Such a dysfunction in storage and release of fatty lipids
      from triglycerides is treated dependent on severity: Patients with slightly
      elevated values (> 200 mg/dl) should change their habits (e.g. balanced diet,
      abstinance of alcohol, exercise) if necessary followed by application of
      fibrates, omega-3 fatty acids or nicotinic acid. These medicamentous measures are
      inevitable and must be applied immediately in case patients having values >1000
      mg/dl.

PMID- 17013581
TI  - [Diabetics in secondary prevention].
AB  - It is well known that diabetics live with a significantly higher incidence of a
      cardiac insufficiency and that acute ischemia is the main cause of death in this
      group (75%). The risk of suffering a myocardial infarction after ischemic
      incidences is significantly higher for diabetics than for patients with normal
      carbohydrate metabolism. Diabetes mellitus is not only responsible for acute
      incidences, but also for a higher incidence of chronic coronary diseases.
      Furthermore a disturbed tolerance glucose value was detected in studies for two
      thirds of the patients which could even be proven after complete rehabilitation.
      It has also been shown that the severity of hyperglycemia is in a close inverse
      relationship to the volume of the brain tissue which can be saved. For this
      reason hyperglycemia is possibly a therapeutic aim in case of acute ischemic
      incidences. Therefore the adjustment of blood sugar should be the primary aim to
      reduce risk in any cases of vascular incidences.

PMID- 17013582
TI  - [Homocysteine as a cardiovascular marker and risk factor].
AB  - In context of cardiovascular secondary prevention the D.A.C.H.-Liga (union of
      scientists from Germany, Austria, and Switzerland doing research on the topic
      homocysteine) demands that the homocysteine level should be measured and
      recommends a substitution of folic acid above a value of 10 micromol/l. Numerous
      studies have proven the therapy's positive effect. Although a threshold could not
      be acquired in any study there seems to be an association between the
      homocysteine level and an increased cardiovascular risk. Homocysteine is not only
      a marker, but also a reason of cardiovascular mortality and morbidity. Further
      detailed statements concerning homocysteine therapy can be made after completing
      of current research.

PMID- 17013583
TI  - [Therapy of hypertension].
AB  - The treatment and management of patients with arterial hypertension depends on
      the global cardiovascular risk of the individual patient. Thus, additional
      cardiovascular risk factors, the presence of target organ damage, cardiovascular
      or renal disease determine not only the initiation of therapy but also the choice
      of drug(s). Drug treatment is usually started with one compound, which is
      selected from 5 drug classes recommended for first-line therapy including ACE
      inhibitors, AT1-antagonists, betablockers, calcium channel blockers, and
      diuretics. Depending on risk and additional disease individual target blood
      pressures are 140/90, 130/80 or 125/75 mmHg, respectively. If blood pressures at
      baseline exceeds target values more than 20/10 mmHg treatment may be started with
      initial or early combination therapy of two drugs. Overall, approximately two
      thirds of patients require treatment with at least two drugs to achieve target
      blood pressure values.

PMID- 17013584
TI  - [Guidelines given by the DSG and DGN concerning stroke therapy--new therapeutic
      aspects].
AB  - Surgeries of symptomatic carotid stenose should not be operated on later than 14
      days after stroke; until the operation inhibitors of platelet aggregation have to
      be administered (Table 1). The application of anticoagulants like warfarin or
      phenprocoumon in case of intracranial stenoses is no longer recommended. Instead
      100-300 mg aspirin should prophylactically be given. The risk of suffering a
      stroke is significantly reduced by the application of antihypertensives. Patients
      with focal cerebral ischemia should be given 40 mg of Simvastatin which leads to
      a significant decrease of vascular risk. After the first cerebral ischemic
      incidenz patients with open foramen ovale of the heart should be given 100-300 mg
      aspirin. In case of aspirin relapse an oral anticoagulation has to be carried out
      with an INR of 2.0 up to 3 for at least one year.

PMID- 17013585
TI  - [Significance of changes in habits followed by risk reduction].
AB  - Cardiovascular risk is substantially influenced by changes in habits. In this
      context the INTERHEART study showed that a healthy vitamin-packed nutrition and
      regular workout reduced the cardiovascular risk up to 79%. In this case people
      older than 50 years would benefit most from change. Patients suffering from
      obesity should combine a low-calory diet with physical training in order to
      reduce weight. Here optimal results can be achieved by considering intensity as
      well as quantity for each patient.

PMID- 17013586
TI  - Cerebral metabolic and structural alterations in hereditary spastic paraplegia
      with thin corpus callosum assessed by MRS and DTI.
AB  - INTRODUCTION: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC)
      is a complicated form of autosomal-recessive hereditary spastic paraplegia.
      Characteristic clinical features comprise progressive spastic gait, cognitive
      impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus
      callosum and non-progressive white matter (WM) alterations. METHODS: To study the
      extent of axonal involvement, we performed localized proton magnetic resonance
      spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient
      with HSP-TCC at 20 and 25 years of age. The second investigation included
      diffusion tensor imaging (DTI). RESULTS: While MRS of the GM was normal, affected
      WM was characterized by major metabolic alterations such as reduced
      concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and
      phosphocreatine, and choline-containing compounds as well as elevated levels of
      myo-inositol. These abnormalities showed progression over a period of 5 years.
      DTI revealed increased mean diffusivity as well as reduced fractional anisotropy
      in periventricular WM. The metabolic and structural findings are consistent with
      progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation
      histopathological changes known to occur in HSP-TCC. CONCLUSION: Our results are
      in agreement with the hypothesis that the primary pathological process in HSP-TCC
      affects the axon, possibly due to impaired axonal trafficking.

PMID- 17013587
TI  - Comparison of first-pass and second-bolus dynamic susceptibility perfusion MRI in
      brain tumors.
AB  - INTRODUCTION: Our goal was to evaluate whether the T1 shortening effect caused by
      contrast leakage into brain tumors, a well-known confounding effect in the
      quantification of relative cerebral blood volume (rCBV) measurements, may be
      corrected by the administration of a predose of gadolinium-DTPA. METHODS: As part
      of their presurgical imaging protocol, 25 patients with primary brain tumors
      underwent two consecutive dynamic susceptibility-weighted contrast-enhanced (DSC)
      perfusion MR studies. Intratumoral rCBV measurements and normalized rCBV values
      obtained during the first-pass and second-bolus studies were compared (Wilcoxon
      signed-ranks test). The frequency of relatively increased rCBV ratios on the
      second-bolus study was compared between enhancing and non-enhancing neoplasms
      (Fisher's exact test). Postprocessing perfusion studies were evaluated for image
      quality on a scale of 0-3 (Wilcoxon signed-ranks test). Four studies were
      excluded due to unacceptable image quality. RESULTS: Mean normalized rCBVs were
      9.04 (SD 4.64) for the first-pass and 7.99 (SD 3.84) for the second-bolus study.
      There was no statistically significant difference between the two perfusion
      studies in either intratumoral rCBV (P=0.237) or rCBV ratio (P=0.181). Five
      enhancing and four non-enhancing tumors showed a relative increase in rCBV ratio
      on the second-bolus study, without a significant difference between the groups.
      Image quality was not significantly different between perfusion studies.
      CONCLUSION: Our results did not demonstrate a significant difference between
      first-pass and second-bolus rCBV measurements in DSC perfusion MR imaging. The
      administration of a predose of gadolinium-DTPA does not appear to be an efficient
      way of compensating for the underestimation of intratumoral rCBV values due to
      the T1 shortening effect.

PMID- 17013588
TI  - Distribution of neuropeptides in the primary olfactory center of the heliothine
      moth Heliothis virescens.
AB  - Neuropeptides are a diverse widespread class of signaling substances in the
      nervous system. As a basis for the analysis of peptidergic neurotransmission in
      the insect olfactory system, we have studied the distribution of neuropeptides in
      the antennal lobe of the moth Heliothis virescens. Immunocytochemical experiments
      with antisera recognizing A-type allatostatins (AST-As), Manduca sexta
      allatotropin (Mas-AT), FMRFamide-related peptides (FaRPs), and tachykinin-related
      peptides (TKRPs) have shown that members of all four peptide families are present
      in local interneurons of the antennal lobe. Whereas antisera against AST-As, Mas
      AT, and FaRPs give similar staining patterns characterized by dense meshworks of
      processes confined to the core of all antennal-lobe glomeruli, TKRPs are present
      only in neurons with blebby processes distributed throughout each glomerulus. In
      addition to local neurons, a pair of centrifugal neurons with cell bodies in the
      lateral subesophageal ganglion, arborizations in the antennal lobe, and
      projections in the inner antenno-cerebral tracts exhibits tachykinin
      immunostaining. Double-label immunofluorescence has detected the co-localization
      of AST-As, Mas-AT, and FaRPs in certain local interneurons, whereas TKRPs occurs
      in a distinct population. MALDI-TOF mass spectrometry has revealed nearly 50 mass
      peaks in the antennal lobe. Seven of these masses (four AST-As, two N-terminally
      extended FLRFamides, and Mas-AT) match known moth neuropeptides. The data thus
      show that local interneurons of the moth antennal lobe are highly differentiated
      with respect to their neuropeptide content. The antennal lobe therefore
      represents an ideal preparation for the future analysis of peptide signaling in
      insect brain.

PMID- 17013589
TI  - Establishment of immortalized dental follicle cells for generating periodontal
      ligament in vivo.
AB  - The dental follicle is a mesenchymal tissue that surrounds the developing tooth
      germ. During tooth root formation, periodontal components, viz., cementum,
      periodontal ligament (PDL), and alveolar bone, are created by dental follicle
      progenitors. Here, we report the presence of PDL progenitors in mouse dental
      follicle (MDF) cells. MDF cells were obtained from mouse incisor tooth germs and
      immortalized by the expression of a mutant human papilloma virus type 16 E6 gene
      lacking the PDZ-domain-binding motif. MDF cells expressing the mutant E6 gene
      (MDF( E6-EGFP ) cells) had an extended life span, beyond 150 population doublings
      (PD). In contrast, normal MDF cells failed to proliferate beyond 10 PD. MDF( E6
      EGFP ) cells expressed tendon/ligament phenotype-related genes such as Scleraxis
      (Scx), growth and differentiation factor-5, EphA4, Six-1, and type I collagen. In
      addition, the expression of periostin was observed. To elucidate the
      differentiation capacity of MDF( E6-EGFP ) cells in vivo, the cells were
      transplanted into severe combined immunodeficiency mice. At 4 weeks, MDF( E6-EGFP
      ) cell transplants had the capacity to generate a PDL-like tissue that expressed
      periostin, Scx, and type XII collagen and the fibrillar assembly of type I
      collagen. Our findings suggest that MDF( E6-EGFP ) cells can act as PDL
      progenitors, and that these cells may be a useful research tool for studying PDL
      formation and for developing regeneration therapies.

PMID- 17013590
TI  - Intensity-dependent effect of body tilt angle on calf muscle fatigue in humans.
AB  - Body tilt angle affects the fatigue of human calf muscle at a high contractile
      force (i.e. 70 %MVC); but the range of forces across which this effect occurs is
      not known and we sought to determine this in the present study. Fourteen men
      performed intermittent calf muscle contractions at either 30, 40, 50 and 60 %MVC
      (Group 1 n = 7) or at 80 and 90 %MVC (Group 2 n = 7). Two tests were performed at
      each intensity in the supine (tilt angle = 0 degrees) and inclined head-up
      position (tilt angle = 67 degrees). MVC was measured prior to and during each
      calf exercise test, and the linear rate of decline in MVC during each test was
      used to estimate muscle fatigue. MVC prior to each test was unaffected by body
      tilt angle in Groups 1 and 2. In Group 1 muscle fatigue was significantly lower
      in the inclined than supine position at 50 %MVC (0.10 +/- 0.05 vs. 0.19 +/- 0.10
      N s(-1)) and 60 %MVC (0.22 +/- 0.20 vs. 0.36 +/- 0.33 N s(-1)); but there was no
      significant difference in fatigue at 30 %MVC (0.07 +/- 0.06 vs. 0.07 +/- 0.07 N
      s(-1)) and 40 %MVC (0.12 +/- 0.07 vs. 0.18 +/- 0.08 N s(-1)). In Group 2, muscle
      fatigue was significantly lower in the inclined compared with the supine position
      at 80 %MVC (0.90 +/- 0.50 vs. 1.49 +/- 0.87 N s(-1)) and 90 %MVC (1.19 +/- 0.47
      vs. 1.79 +/- 0.78 N s(-1)). These data demonstrate that the postural effect on
      calf muscle fatigue during intermittent contractions is manifest at moderate to
      very high forces, but that it does not occur at low forces.

PMID- 17013591
TI  - Relationships between pulse wave velocity and heart rate variability in healthy
      men with a range of moderate-to-vigorous physical activity levels.
AB  - Pulse wave velocity (PWV) is associated with heart rate variability (HRV) in 24
      39-year-old men. This study of 40-65-year-old men ranging in moderate-to-vigorous
      physical activity levels investigated whether (a) PWV is related to spectral HRV,
      (b) using normalised units for HRV influences that relationship, and (c) HRV
      predicts PWV when other factors, including age and blood pressure, are accounted
      for. Subjects were healthy men (N=115), mean (SD) age 50.8 (7.1) years. Carotid
      femoral PWV was measured using Complior. HRV was derived from a 5 min ECG for
      total, high-frequency, and low-frequency power (TP, HF, and LF, respectively),
      the LF/HF ratio, and normalised units for HF (HFnu) and LF (LFnu). Non-parametric
      data were natural log-transformed. PWV was 8.5 (1.4) m s-1. TP, HF, LF, LF/HF,
      HFnu and LFnu were 1908 (2195) m s2, 577 (1034) m s2, 457 (514) m s2, 1.5 (1.3),
      46.8 (17.9), and 49.4 (19.4), respectively. PWV was inversely associated with TP
      (R2=0.061, p=0.008), HF (R2=0.095, p=0.001), LF (R2=0.086, p=0.002) and HFnu
      (R2=0.040, p=0.031), but was not associated with LF/HF (R2=0.020, p=0.136) or
      LFnu (R2=0.028 p=0.076). Only age and systolic blood pressure (adjusted R2=0.306,
      p<0.001) predicted PWV in multivariate analysis. This study has shown that PWV
      was weakly associated with TP and HF. The use of normalised units only influenced
      the relationship between PWV and LF. Finally, relationships between PWV and HRV
      are mediated through age and systolic blood pressure in this population of men
      ranging in moderate-to-vigorous physical activity level.

PMID- 17013592
TI  - [Recurrent transient ischaemic attacks in a patient with pansinusitis].
AB  - A 31-year-old woman presented with neurological deficits after an operation for
      sinusitis. The cranial MRI revealed multiple ischaemic lesions. Laboratory
      results showed a hypereosinophilia as well as elevated creatine kinase and
      troponin levels. The ECG implied ST elevations, the left ventricular ejection
      fraction was highly reduced and the cardiac MRI was suspicious for
      endomyocarditis. The cardiac biopsy demonstrated the findings of Loeffler's
      endocarditis. In conclusion the diagnosis of hypereosinophilic syndrome was made
      and identified as the cause of the neurological deficits.

PMID- 17013593
TI  - Detection of small pulmonary nodules in high-field MR at 3 T: evaluation of
      different pulse sequences using porcine lung explants.
AB  - To evaluate two MR imaging sequences for the detection of artificial pulmonary
      nodules inside porcine lung explants. 67 agarose nodules ranging 3-20 mm were
      injected into ten porcine lungs within a dedicated chest phantom. The signal on
      T1-weighted images and radiopacity were adjusted by adding 0.125 mmol/l Gd-DTPA
      and 1.5 g/l of iodine. A T1-weighted three-dimensional gradient-echo (T1-3D-GRE;
      TR/TE:3.3/1.1 ms, slice:8 mm, flip-angle:10 degrees ) and a T2-weighted half
      Fourier fast-spin echo sequence (T2-HF-FSE; TR/TE:2000/66 ms, slice:7 mm, flip
      angle:90 degrees ) were applied in axial orientation using a 3-T system (Intera,
      Philips Medical Systems, Best, The Netherlands), followed by CT (16x0.5 mm) as
      reference. Nodule sizes and locations were assessed by three blinded observers.
      In nodules of >10 mm, sensitivity was 100% using 3D-GRE-MRI and 94% using the HF
      FSE sequence. For nodules 6-10 mm, the sensitivity of MRI was lower than with CT
      (3D-GRE:92%; T2-HF-FSE:83%). In lesions smaller than 5 mm, the sensitivity
      declined to 80% (3D-GRE) and 53% (HF-FSE). Small lesion diameters were
      overestimated with both sequences, particularly with HF-FSE. This study confirms
      the feasibility of 3 T-MRI for lung nodule detection. In lesions greater than 5
      mm, the sensitivity of the 3D-GRE sequence approximated CT (>90%), while
      sensitivity and PPV with the HF-FSE sequence were slightly inferior.

PMID- 17013594
TI  - The impact of the dosage of intravenous gadolinium-chelates on the vascular
      signal intensity in MR angiography.
AB  - To show the effects of different concentrations of contrast agent on signal time
      curves and image contrast of abdominal aorta, vena cava and portal vein in
      comparison to each other as well as liver and spleen. Imaging was carried out in
      a 1.0 Tesla clinical scanner. Sixty patients were prospectively included and
      divided into three contrast agent (Gd-DTPA) dosage groups (0.1 mmol/kg, 0.2
      mmol/kg and 0.3 mmol/kg). All patients were scanned using a time-resolved 3D
      FLASH sequence (58 phases) with a 3.75 second acquisition time per phase. Signal
      time curves and image contrast levels were evaluated. No significant differences
      were found for the maximum signal enhancement between the groups in the
      investigated vessels. Image masking, the subtraction of the baseline images,
      resulted in a substantial improvement in image contrast. However, statistically
      significant differences between the contrast agent dosage groups could only be
      found for vena cava and liver. Vessel conspicuity is not significantly improved
      with an increase of contrast agent dose. However, an increase in contrast agent
      dosage increases vessel contrast. Our findings suggest that a single dose single
      station investigation seems to be sufficient for high quality abdominal MRA.

PMID- 17013597
TI  - Recombinant chromosome 4 resulting from a maternal pericentric inversion in two
      sisters presenting consistent dysmorphic features.
AB  - The chromosome 4 inversion with breakpoints p13-p15q35 results in a recombinant 4
      [rec(4)] chromosome with a partial 4p duplication/4q deletion in approximately
      80% of the carriers' offspring. However, whether the recombinant 4p syndrome can
      be recognized as a clinical entity is still open to controversy. We report on two
      sisters diagnosed with rec(4) resulting in a partial 4p trisomy/4q deletion that
      was inherited from their mother, who is a carrier of inv(4)(p14q35). Both
      probands presented phenotypes consistent with those observed in other children
      with rec(4)parental, supporting the proposal that the rec(4)parental syndrome is
      a distinct entity among dup(4p) cases and may be suspected on the basis of the
      pattern of clinical symptoms. To the best of our knowledge this is only the
      second report of family with two probands affected with a recombinant chromosome
      4 arising from a parental pericentric inversion.

PMID- 17013596
TI  - Potential use of procalcitonin concentrations as a diagnostic marker of the PFAPA
      syndrome.

PMID- 17013595
TI  - Guidelines from the European Society of Breast Imaging for diagnostic
      interventional breast procedures.
AB  - The aim of the breast team is to obtain a definitive, nonoperative diagnosis of
      all potential breast abnormalities in a timely and cost-effective way.
      Percutaneous needle biopsy with its high sensitivity and specificity should now
      be standard practice, removing the need for open surgical biopsy or frozen
      section. For patients with cancer, needle biopsy provides a cost-effective and
      rapid way of providing not only a definitive diagnosis but prognostic
      information, allowing prompt discussion of treatment options, be they surgical or
      medical. Early removal of uncertainty also allows better psychosocial adjustment
      to the disease. Patients with benign conditions found either by themselves or as
      a result of population or opportunistic screening can be promptly reassured and
      discharged, removing the health care and psychological costs of surgical biopsy
      or repeated follow-up. Radiologists involved in breast imaging should ensure that
      they have the necessary skills to carry out core biopsy and/or fine-needle
      aspiration (FNA) under all forms of image guidance. This paper provides
      guidelines on best practice for diagnostic interventional breast procedures and
      standards, against which all practitioners should audit themselves, from the
      European Society of Breast Imaging.

PMID- 17013598
TI  - Coupling between carbon cycling and climate in a high-elevation, subalpine
      forest: a model-data fusion analysis.
AB  - Fundamental questions exist about the effects of climate on terrestrial net
      ecosystem CO(2) exchange (NEE), despite a rapidly growing body of flux
      observations. One strategy to clarify ecosystem climate-carbon interactions is to
      partition NEE into its component fluxes, gross ecosystem CO(2) exchange (GEE) and
      ecosystem respiration (R (E)), and evaluate the responses to climate of each
      component flux. We separated observed NEE into optimized estimates of GEE and R
      (E) using an ecosystem process model combined with 6 years of continuous flux
      data from the Niwot Ridge AmeriFlux site. In order to gain further insight into
      the processes underlying NEE, we partitioned R (E) into its components:
      heterotrophic (R (H)) and autotrophic (R (A)) respiration. We were successful in
      separating GEE and R (E), but less successful in accurately partitioning R (E)
      into R (A) and R (H). Our failure in the latter was due to a lack of adequate
      contrasts in the assimilated data set to distinguish between R (A) and R (H). We
      performed most model runs at a twice-daily time step. Optimizing on daily
      aggregated data severely degraded the model's ability to separate GEE and R (E).
      However, we gained little benefit from using a half-hourly time step. The model
      data fusion showed that most of the interannual variability in NEE was due to
      variability in GEE, and not R (E). In contrast to several previous studies in
      other ecosystems, we found that longer growing seasons at Niwot Ridge were
      correlated with less net CO(2) uptake, due to a decrease of available snow-melt
      water during the late springtime photosynthetic period. Warmer springtime
      temperatures resulted in increased net CO(2) uptake only if adequate moisture was
      available; when warmer springtime conditions led into mid-summer drought, the
      annual net uptake declined.

PMID- 17013599
TI  - Isotopic insight into host-endosymbiont relationships in Liolaemid lizards.
AB  - Nitrogen isotopes have been widely used to investigate trophic levels in
      ecological systems. Isotopic enrichment of 2-5 per thousand occurs with trophic
      level increases in food webs. Host-parasite relationships deviate from
      traditional food webs in that parasites are minimally enriched relative to their
      hosts. Although this host-parasite enrichment pattern has been shown in multiple
      systems, few studies have used isotopic relationships to examine other potential
      symbioses. We examined the relationship between two gut-nematodes and their
      lizard hosts. One species, Physaloptera retusa, is a documented parasite in the
      stomach, whereas the relationship of the other species, Parapharyngodon riojensis
      (pinworms), to the host is putatively commensalistic or mutualistic. Based on the
      established trophic enrichments, we predicted that, relative to host tissue,
      parasitic nematodes would be minimally enriched (0-1 per thousand), whereas
      pinworms, either as commensals or mutualists, would be significantly enriched by
      2-5 per thousand. We measured the (15)N values of food, digesta, gut tissue, and
      nematodes of eight lizard species in the family Liolaemidae. Parasitic worms were
      enriched 1+/-0.2 per thousand relative to host tissue, while the average
      enrichment value for pinworms relative to gut tissue was 6.7+/-0.2 per thousand.
      The results support previous findings that isotopic fractionation in a host
      parasite system is lower than traditional food webs. Additionally, the larger
      enrichment of pinworms relative to known parasites suggests that they are not
      parasitic and may be several trophic levels beyond the host.

PMID- 17013600
TI  - A simple method for extracting C-phycocyanin from Spirulina platensis using
      Klebsiella pneumoniae.
AB  - C-phycocyanin (C-PC) was extracted from fresh Spirulina platensis by deploying a
      species of non-pathogenic nitrogen-fixing bacteria, namely, Klebsiella
      pneumoniae. The algal slurry was neither washed nor centrifuged; the bacterial
      culture was poured into the slurry, the vessel sealed, and crude C-PC extracted
      after about 24 h. The extraction was clean and efficient, and the purity and
      concentration of C-PC proved to be of adequate quality.

PMID- 17013601
TI  - The aureolic acid family of antitumor compounds: structure, mode of action,
      biosynthesis, and novel derivatives.
AB  - Members of the aureolic acid family are tricyclic polyketides with antitumor
      activity which are produced by different streptomycete species. These members are
      glycosylated compounds with two oligosaccharide chains of variable sugar length.
      They interact with the DNA minor groove in high-GC-content regions in a
      nonintercalative way and with a requirement for magnesium ions. Mithramycin and
      chromomycins are the most representative members of the family, mithramycin being
      used as a chemotherapeutic agent for the treatment of several cancer diseases.
      For chromomycin and durhamycin A, antiviral activity has also been reported. The
      biosynthesis gene clusters for mithramycin and chromomycin A(3) have been studied
      in detail by gene sequencing, insertional inactivation, and gene expression. Most
      of the biosynthetic intermediates in these pathways have been isolated and
      characterized. Some of these compounds showed an increase in antitumor activity
      in comparison with the parent compounds. A common step in the biosynthesis of all
      members of the family is the formation of the tetracyclic intermediate
      premithramycinone. Further biosynthetic steps (glycosylation, methylations,
      acylations) proceed through tetracyclic intermediates which are finally converted
      into tricyclic compounds by the action of a monooxygenase, a key event for the
      biological activity. Heterologous expression of biosynthetic genes from other
      aromatic polyketide pathways in the mithramycin producer (or some mutants) led to
      the isolation of novel hybrid compounds.

PMID- 17013602
TI  - Hydroxyapatite porous coating and the osteointegration of the total hip
      replacement.
AB  - INTRODUCTION: The main purpose of this study is to evaluate the efficacy of the
      plasma sprayed, combined porous titanium alloy/HA coating in promoting bony
      ingrowth and mechanical stabilization of total hip implants. The performance of
      the titanium alloy/HA type coated hip prostheses and the one of the same shape
      but without any coating, is compared in this paper. MATERIAL AND METHODS: The
      implants were manufactured from titanium alloy VT-6 (ASTM F-136). The hip stems
      utilized in the control group were identical to those subsequently coated. The
      coating consists of a plasma deposited first layer of porous titanium alloy
      (TiAl(6)V(4)), similar in composition to the forged substrate and a plasma
      deposited second layer of over-sprayed hydroxyapatite, Ca(10)(PO(4))6(OH)2.
      Coating is located in the critical area of the hip stems, where high fixation
      interface strength is desired, i.e. in the proximal area of the stem where the
      highest stresses occur. The porous titanium alloy/hydroxyapatite (HA) coated
      femoral stems were implanted in 50 patients. The results were compared with a
      control group of 50 patients with the same type of endoprosthesis, but without
      the porous titanium alloy/HA coating. Both groups of patients were operated on
      and evaluated by the same orthopedic surgeons with a mean follow up of 11.4 years
      in the HA group and 10.6 years in the control group. RESULTS: HHS in the control
      group was preoperatively 35.5 points (range 26-49) and 85.1 points (range 54-100)
      in the time of the last control. HHS in the HA group was preoperatively 34.1
      points (range 27-56) and 94.4 points (range 89-100) in the time of the last
      control. In 28 cases (56%) of the control group a range of translucencies were
      obvious. These translucent lines, however, did not appear with any of the
      patients in the coated implant group except one infection stem migration.
      CONCLUSION: Experience with the HA-type coated hip implants demonstrates
      substantially higher degree and quality of osteointegration in the porous
      titanium alloy/HA type implants.

PMID- 17013603
TI  - Epidemiology of hip fractures in Belgrade, Serbia Montenegro, 1990-2000.
AB  - INTRODUCTION: This study retrospectively determined the incidence rates of hip
      fractures in Belgrade, Serbia and Montenegro, during the period 1990-2000.
      MATERIALS AND METHODS: All patients with hip fractures treated at all Belgrade
      hospitals were identified from the Republic of Serbia's Ministry of Health
      National Health Care database. Patient demographics, type of hip fracture, and
      details of the mechanism of injury were collected. The annual incidence rates
      were calculated with interpolation according to the Belgrade population census of
      1991 and 2002. RESULTS: There were a total of 8,904 hip fractures with a mean
      annual incidence of 51.7 per 100,000 adults (62.2 females and 35.5 males). Mean
      age at the time of fracture was 67 years (72.6 for females and 59.3 for males),
      with 64.7% of all fractures occurring in women. There was a significant increase
      in hip fracture incidence rates over the observed period in females (P = 0.006),
      but not in males (P = 0.962). Trochanteric fractures predominated, accounting for
      53% compared with cervical fractures. In patients over 50 years of age there was
      an exponential increase in the incidence of hip fractures in both sexes; though
      more so in females. 91% of hip fractures occurred in these older patients with
      incidence rates of 143.6 per 100,000 (185.9 for female and 92.2 for male
      patients). The most common mechanism of injury in the older group was low-energy
      trauma (70.3%) resulting from a fall from standing height onto a flat surface
      (same level). Standardizing incidence rates in the older age group to the US 1985
      white population gave values of 228 per 100,000 females and 96 per 100,000 males.
      These incidence rates are similar to those reported in Italy, France and Great
      Britain, but lower than those in Scandinavian countries. CONCLUSION: In view of
      growing population numbers and an increase in the proportion of patients aged
      over 60 years, we can expect an increase in the prevalence of osteoporosis and an
      increase in the incidence of fragility hip fractures in the future, with resource
      implications.

PMID- 17013604
TI  - Results of primary extensor tendon repair in relation to the zone of injury and
      pre-operative outcome estimation.
AB  - INTRODUCTION: The outcome of primary extensor repair in hand surgery has been
      widely explored, but little systematic effort has been made to investigate the
      influence of the anatomical zone of tendon injury. Therefore, the aim of our
      study was to assess the outcome of primary extensor tendon repair with a special
      focus on the pre-operative state and Verdan's anatomical zones. Our hypothesis
      being tested was that the outcome after primary extensor repair depends on the
      complexity of trauma and the site of lesion. MATERIALS AND METHODS: One hundred
      and seventy seven patients with 203 extensor tendon repairs were studied. After
      tendon repair and a 6-week protective immobilization, physiotherapy was carried
      out. A score proposed by Geldmacher and Schwarzbach was applied to estimate the
      outcome pre-operatively and to assess the results in a follow-up after a mean of
      13 months. Correlations were tested between the anatomical zone of tendon injury,
      the pre-operative expectation and the results as considered both by the patient
      and the physician. RESULTS: In Verdan's zones 1, 2, 4 and 5, excellent or good
      results were obtained in the vast majority of patients. Due to a higher frequency
      of complex injuries with concomitant soft tissue and bony injuries, the outcome
      was significantly worse after tendon repair in zones 3 and 6, as expected after
      the pre-operative estimation. In addition, a strong correlation was found for all
      anatomical zones between the pre-operative estimation and the outcome as judged
      both by the physician and the patient. CONCLUSION: Recovery of finger function
      after primary extensor tendon repair depends on the complexity of trauma and the
      anatomical zone of tendon injury. Static splinting is an appropriate tool after
      primary extensor tendon repair in Verdan's zone 1, 2, 4 and 5, whereas injuries
      in zones 3 and 6 may demand for a different treatment regimen.

PMID- 17013605
TI  - Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and
      atherosclerosis evolves from activation of the inflammatory cascade. We propose
      that activation of the nuclear factor kappaB (NF-kappaB), a key transcription
      factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking,
      and non-hypertensive men with OSA symptoms and seven similar healthy subjects
      were recruited for standard polysomnography followed by the collection of blood
      samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the
      OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF
      alpha) were measured at the same time and after the next night of continuous
      positive airway pressure (CPAP). p65 Concentrations in the OSA group were
      significantly higher than in the control group [median, 0.037 ng/microl
      (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range,
      0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated
      with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r =
      0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP
      resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to
      0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26
      (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to
      12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing.
      Such activation of NF-kappaB may contribute to the pathogenesis of
      atherosclerosis in OSA patients.

PMID- 17013606
TI  - Estimating absolute glomerular filtration rate in children.
AB  - Normal values of glomerular filtration rate (GFR) in children are often expressed
      in a value adjusted to adult ideal body surface area. These values work well for
      many clinical situations, but in infants and children, especially those with
      atypical body mass, they may not accurately reflect renal function. Most body
      composition values in children are expressed in developmentally appropriate
      ranges. Absolute GFR (ml/min) also changes during childhood increasing rapidly in
      infancy and then gradually with age and body size. Previously, we developed a
      bedside equation for estimating GFR (ml/min) in children that accounted for
      changes with age and body size, and which correlated well with steady-state cold
      iothalamate GFR (ml/min) measurements: GFR (ml/min) = k(*)sqrt[(age(months) +
      6)*wt (kg)/serum Cr (mg/dl)], where k=0.95 for females and 1.05 for males. In the
      present study GFR (ml/min) measured by iothalamate infusion was compared by
      correlation analysis with estimates calculated from the above equation in 566
      children. This equation provides clinicians with a simple bedside method to
      estimate absolute GFR (ml/min).

PMID- 17013607
TI  - The prevalence of Tropheryma whippelii DNA in saliva from healthy controls and
      patients with spondyloarthropathy.

PMID- 17013608
TI  - Rhodococcus equi infection during treatment of a c-ANCA positive vasculitis: a
      case report.
AB  - Rhodococcus equi is a rare form of opportunistic infection in humans, more common
      in the immunocompromised. We present a case of pulmonary infection and subsequent
      cerebral abscess secondary to R. equi in a patient receiving immunosuppression
      for a c-ANCA positive vasculitis. Heightened awareness of R. equi infection is
      important when considering immunocompromised patients presenting with sepsis,
      especially those with cavitating pulmonary lesions and normal respiratory
      commensals on culture. Delays in diagnosis and treatment can cause increased
      patient morbidity and mortality.

PMID- 17013609
TI  - Role of amyloidosis in determining the prognosis of dialyzed patients with
      rheumatoid arthritis.
AB  - The role of secondary amyloidosis in determining the prognosis of dialyzed
      patients with rheumatoid arthritis (RA) was examined in 22 patients with a mean
      age of 60.1 years included 21 renal amyloidosis. RA duration until the start of
      dialysis was 19.5 +/- 7.2 years and the observation period after introduction
      27.1 +/- 26.4 months. Of the 14 dead cases, four died due to sepsis, three due to
      gastrointestinal tract bleeding, two due to congestive heart failure, and eight
      cases died within 5 months after starting dialysis. When comparing the eight
      survivors and the nine non-survivors who died within 2 years after the start of
      dialysis, the former patients showed significantly higher serum albumin, and
      lower electrocardiogram score and cardiothoracic ratios at the time of
      introduction to dialysis. The careful prevention and treatment of infection,
      cerebrovascular and/or gastrointestinal tract complications seem to be necessary
      to improve the prognosis of RA patients after the initiation of renal replacement
      therapy.

PMID- 17013610
TI  - Expression patterns of Hox genes in larvae of the sea lily Metacrinus rotundus.
AB  - We cloned eight Hox genes (MrHox1, MrHox2, MrHox4, MrHox5, MrHox7, MrHox8,
      MrHox9/10, and MrHox11/13c) from the sea lily Metacrinus rotundus, a member of
      the most basal group of the extant echinoderms. At the auricularia stage, before
      the formation of the pentaradial rudiment, four MrHox genes were expressed
      sequentially along the anteroposterior (AP) axis in the straightened mesodermal
      somatocoels in the order MrHox5, MrHox7, MrHox8, and MrHox9/10. The expression of
      MrHox7 and MrHox8 was detected as early as the hatching stage in the presumptive
      somatocoel region of the archenteral sac. MrHox5 was expressed in the
      anteriormost region of the somatocoels, where a stalk-related structure (the
      chambered organ) forms later. In addition to the mesodermal somatocoels, MrHox7
      was expressed in the oral hood ectoderm, which gives rise to the adhesive pit.
      The expression of four other MrHox genes (MrHox1, MrHox2, MrHox4, and
      MrHox11/13c) was not detected in any of the larval stages we examined. In
      comparison with the mesodermal sea urchin Hox genes, the MrHox genes are
      expressed more posteriorly along the AP (oral-anal) axis than the sea urchin
      orthologs, implying that the evolution of the eleutherozoans was accompanied by a
      posteriorization of the larval body. Our study illuminates the possible body plan
      and Hox expression patterns of the ancestral echinoderm and sheds light on the
      larval body plan of the last common ancestor of the echinoderms and chordates.

PMID- 17013611
TI  - Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in
      epilepsy-associated Taylor-type focal cortical dysplasias.
AB  - Focal cortical dysplasias (FCD) with Taylor-type balloon cells (FCD(IIb)) are
      frequently observed in biopsy specimens of patients with pharmacoresistant focal
      epilepsies. The molecular pathogenesis of FCD(IIb), which lack familial
      inheritance, is only poorly understood. Due to their highly differentiated,
      malformative nature and glioneuronal phenotype, FCD(IIb) share neuropathological
      characteristics with lesions observed in familial disorders such as cortical
      tubers present in patients with autosomal dominant tuberous sclerosis complex
      (TSC), related to mutations in the TSC1 or TSC2 genes, and dysplastic
      gangliocytomas of the cerebellum found in Cowden disease. Current data have
      indicated distinct allelic variants of TSC1 to accumulate in FCD(IIb). TSC1
      represents a tumor suppressor operating in the phosphatidylinositol 3-kinase
      (PI3K)/insulin pathway. The tumor-suppressor gene PTEN is mutated in Cowden
      disease. Like PTEN, also carboxyl-terminal modulator protein (CTMP) modulates
      PI3K-pathway signaling, both via inhibition of Akt/PKB, a kinase inactivating the
      TSC1/TSC2 complex. Here, we have analyzed alterations of Akt, PTEN and CTMP
      relevant for insulin signaling upstream of TSC1/TSC2 in FCD(IIb).
      Immunohistochemistry with antibodies against phosphorylated Akt (phospho-Akt; Ser
      473) in FCD(IIb) (n=23) showed strong phospho-Akt expression in dysplastic
      FCD(IIb) components. We have further studied sequence alterations of PTEN (n=34
      FCD(IIb)) and CTMP (n=20 FCD(IIb)) by laser microdissection/single-strand
      conformation polymorphism analysis. We observed a somatic mutation in an
      FCD(IIb), i.e., amino-acid exchange at nucleotide position 834 (PTEN cDNA,
      GenBank AH007803.1) in exon 8 with replacement of phenylalanine by leucine
      (F278L). We also found several silent polymorphisms of PTEN in exon 2 and exon 8
      as well as silent and coding polymorphisms but no mutations in CTMP. No loss of
      heterozygosity in FCD(IIb) (n=6) at 10q23 was observed. To our knowledge, we here
      report on the first somatic mutation of a tumor-suppressor gene, i.e., PTEN, in
      FCD(IIb). However, our study also demonstrates that mutational alterations of
      PTEN and CTMP do not play major pathogenetic roles for activation of Akt in
      FCD(IIb). Future studies need to determine the origin of insulin pathway
      activation upstream of TSC1/TSC2 in FCD(IIb).

PMID- 17013612
TI  - Can (hyperbaric) oxygen turn off the motor of multiorgan dysfunction?

PMID- 17013613
TI  - Isolation of Zn-responsive genes from two accessions of the hyperaccumulator
      plant Thlaspi caerulescens.
AB  - Several populations with different metal tolerance, uptake and root-to-shoot
      transport are known for the metal hyperaccumulator plant Thlaspi caerulescens. In
      this study, genes differentially expressed under various Zn exposures were
      identified from the shoots of two T. caerulescens accessions (calaminous and non
      calaminous) using fluorescent differential display RT-PCR. cDNA fragments from 16
      Zn-responsive genes, including those encoding metallothionein (MT) type 2 and
      type 3, MRP-like transporter, pectin methylesterase (PME) and Ole e 1-like gene
      as well as several unknown genes, were eventually isolated. The full-length MT2
      and MT3 sequences differ from those previously isolated from other Thlaspi
      accessions, possibly representing new alleles or isoforms. Besides the
      differential expression in Zn exposures, the gene expression was dependent on the
      accession. Thlaspi homologues of ClpP protease and MRP transporter were induced
      at high Zn concentrations. MT2 and PME were expressed at higher levels in the
      calaminous accession. The MTs and MRP transporter expressed in transgenic yeasts
      were capable of conferring Cu and Cd tolerance, whereas the Ole e 1-like gene
      enhanced toxicity to these metals. The MTs increased yeast intracellular Cd
      content. As no significant differences were found between Arabidopsis and Thlaspi
      MTs, they apparently do not differ in their capacity to bind metals. However, the
      higher levels of MT2 in the calaminous accession may contribute to the Zn-adapted
      phenotype.

PMID- 17013615
TI  - Metabolic design of macroscopic bioreaction models: application to Chinese
      hamster ovary cells.
AB  - The aim of this paper is to present a systematic methodology to design
      macroscopic bioreaction models for cell cultures based upon metabolic networks.
      The cell culture is seen as a succession of phases. During each phase, a
      metabolic network represents the set of reactions occurring in the cell. Then,
      through the use of the elementary flux modes, these metabolic networks are used
      to derive macroscopic bioreactions linking the extracellular substrates and
      products. On this basis, as many separate models are obtained as there are
      phases. Then, a complete model is obtained by smoothly switching from model to
      model. This is illustrated with batch cultures of Chinese hamster ovary cells.

PMID- 17013614
TI  - Ab initio modelling of the structure and redox behaviour of copper(I) bound to a
      His-His model peptide: relevance to the beta-amyloid peptide of Alzheimer's
      disease.
AB  - A contributing factor to the pathology of Alzheimer's disease is the generation
      of reactive oxygen species, most probably a consequence of the beta-amyloid
      (Abeta) peptide coordinating copper ions. Experimental and theoretical results
      indicate that His13 and His14 are the two most firmly established ligands in the
      coordination sphere of Cu(II) bound to Abeta. Abeta1-42 is known to reduce Cu(II)
      to Cu(I). The Abeta-Cu(II) complex has been shown to catalytically generate
      H(2)O(2) from reducing agents and O(2). Cu(II) in the presence of Abeta has been
      reported to have a formal reduction potential of +0.72-0.77 V (vs. the standard
      hydrogen electrode). Quantum chemical calculations using the B3LYP hybrid density
      functional method with the 6-31G(d) basis set were performed to model the
      reduction of previously studied Cu(II) complexes representing the His13-His14
      portion of Abeta (Raffa et al. in J. Biol. Inorg. Chem. 10:887-902, 2005). The
      effects of solvation were accommodated using the CPCM method. The most stable
      complex between Cu(I) and the model compound, 3-(5-imidazolyl)propionylhistamine
      (1) involves tricoordinated Cu(I) in a distorted-T geometry, with the Npi of both
      imidazoles as well as the oxygen of the backbone carbonyl bound to copper. This
      model would be the most likely representation of a Cu(I) binding site for a His
      His peptide in aqueous solution. A variety of possible redox processes are
      discussed.

PMID- 17013616
TI  - Cell-mass maximization in fed-batch cultures: sufficient conditions for singular
      arc and optimal feed rate profiles.
AB  - Complete solutions are provided for cell-mass maximization for free and fixed
      final times and constant and variable yields. The optimal feed rate profile is a
      concatenation of maximum, minimum and singular feed rates. The exact sequence and
      duration of each feed rate depends primarily on the initial substrate
      concentration, and degenerate cases arise due to the magnitude constraint on the
      feed rate and the length of final time t (f). When the final time is free and not
      in the performance index, it is infinite for constant yield so that any form of
      feed rate leads to the same amount of cells, while for variable yield the
      singular feed rate is exponential and maximizes the yield. For fixed final time
      the singular feed rate for constant yield is exponential and maximizes the
      specific growth rate by maintaining the substrate concentration constant, while
      for variable yield, it is semi-exponential and the substrate concentration starts
      near the maximum specific growth rate and moves toward the maximum yield. A
      simple sufficient condition for existence of singular feed rate requires an
      existence of a region bounded by the maxima of specific growth and cellular
      yield. Otherwise, the optimal feed rate profile is a bang-bang type and the
      bioreactor operates in batch mode.

PMID- 17013617
TI  - CAPs markers to assist selection for low vicine and convicine contents in faba
      bean (Vicia faba L.).
AB  - The antinutritional factors (ANFs) present in Vicia spp. seeds are a major
      constraint to the wider utilization of these crops as grain legumes. In the case
      of faba bean (Vicia faba L.), a breeding priority is the absence vicine and
      convicine (v-c); responsible for favism in humans and for the reduced animal
      performance or low egg production in laying hens. The discovery of a spontaneous
      mutant allele named vc-, which induces a 10-20 fold reduction of v-c contents,
      may facilitate the process. However, the high cost and difficulty of the chemical
      detection of v-c seriously restricts the advances in breeding-selection. To
      identify random amplified polymorphic DNA (RAPD) markers linked to this gene, we
      have analysed an F(2 )population derived from a cross between a line with high v
      c content (Vf6) and the vc- genotype (line 1268). Quantification of v-c was done
      by spectrophotometry on the parents and the F(2 )population (n = 136). By using
      bulked segregant analysis (BSA), two RAPD markers linked in coupling and
      repulsion phase to the allele vc- were identified and further converted into
      sequence characterized amplified regions (SCARs). Amplification of SCARS was more
      consistent, although the initial polymorphism between pools was lost. To recover
      the polymorphisms several approaches were explored. Restriction digestion with
      HhaI (for SCAR SCH01(620)) and RsaI (for SCAR SCAB12(850)) revealed clear
      differences between the parental lines. The simultaneous use of the two cleavage
      amplified polymorphism (CAP) markers will allow the correct fingerprinting of
      faba bean plants and can be efficiently used in breeding selection to track the
      introgression of the vc- allele to develop cultivars with low v-c content and
      improved nutritional value.

PMID- 17013618
TI  - Time to reconfigure balancing behaviour in man: changing visual condition while
      riding a continuously moving platform.
AB  - While balancing on a continuously antero-posterior (A-P) translating platform (10
      cm, 0.5 Hz), the head normally oscillates with the platform without vision but is
      stabilized in space with vision. We estimated the time to shift from one to the
      other balancing behaviour when visual condition changed at some stage during the
      balancing trials. Ten subjects performed randomly 50 balancing trials (each
      lasting 18 s): 10 trials with eyes open (EO), 10 with eyes closed (EC), 15 in
      which participants started with EO and closed their eyes (condition EO-->EC) in
      response to an acoustic signal delivered during the trial, and 15 starting with
      EC and closing their eyes (EC-->EO) in response to the same signal. No other
      specific instruction was given. Displacements of malleolus, hip and head, and EMG
      from leg and axial muscles were recorded. Indexes of amplitude of A-P head and
      hip oscillation and of amplitude of EMG activity were computed. All variables
      were larger with EC than EO. On changing visual condition during the trial, the
      pattern of head and hip movement and of muscle activity turned into that
      appropriate for the new visual condition in a time-interval ranging from about 1
      to 2.5 s. For each subject, the mean latency of the change in the balancing
      behaviour was assessed by statistical methods. On average, the latencies of
      kinematics and EMG changes proved to be longer for the EO-->EC condition than
      vice versa. Further, the latencies of the changes were also measured across all
      EO-->EC and EC-->EO individual trials. These values were clustered around
      particular epochs of the first few oscillation cycles following the shift in
      visual condition. The results show that subjects can rapidly adapt their
      balancing behaviour to the new visual condition. However, they appear to refrain
      from releasing the new behaviour were this unfit, and unfastened it at
      appropriate time in the next platform translation cycle. These findings reveal
      the temporal and spatial features of the automatic release of the new balancing
      strategy in response to a shift in the ongoing sensory set, and emphasize the
      swiftness in the change in balancing behaviour when subjects pass from a non
      visual to a visual reference frame.

PMID- 17013620
TI  - Expression of the avian gene cNOC2 encoding nucleolar complex associated protein
      2 during embryonic development.
AB  - Genetic information that directs a cell during different phases of embryogenesis
      is locked up in the genome. Therein is contained the road map for growth,
      proliferation, differentiation and morphogenesis. The cellular transportation
      machinery plays a major role to ensure that all the components for transcription
      and translation are available at the right place at the right time. Nucleolar
      complex associated protein2 (NOC2) has a highly conserved UPF0120 domain, and is
      an element involved in ribosome transportation from the nucleoplasm to the
      cytoplasm. However, its gene expression pattern is still unknown. We chose the
      developing chick embryo to investigate the possible involvement of avian NOC2
      (cNOC2) in developmental processes, particularly neurogenesis and myogenesis. For
      this purpose, we constructed a fragment of chicken cNOC2, which contains the
      UPF0120 domain coding sequence, into pDrive vector, and performed in situ
      hybridization on chicken embryos of different stages with this gene probe. A
      dynamic expression pattern of cNOC2 transcripts can be seen beginning as early as
      from stage HH7 until stage HH32. Using in situ hybridization we could detect that
      cNOC2 transcripts were expressed ubiquitously, but prominent expression could be
      found in the neural tissue, the somites and in the developing limbs. Comparison
      of cNOC2 gene expression with the proliferation marker gene cPCNA, muscle
      specific marker genes cMyf5 and cMyoD in single or double in situ hybridisation
      show that cNOC2 is expressed in the myotome, similar to cMyf5 and cMyoD, but not
      like cPCNA, which is hardly detectable in the myotome. Our results suggest that
      cNOC2 is involved in the development of neural tissue, somites and limbs.

PMID- 17013619
TI  - Time of transplantation and cell preparation determine neural stem cell survival
      in a mouse model of Huntington's disease.
AB  - Cell replacement therapies for neurodegenerative diseases, using multipotent
      neural stem cells (NSCs), require above all, a good survival of the graft. In
      this study, we unilaterally injected quinolinic acid (QA) into the striatum of
      adult mice and transplanted syngeneic NSCs of enhanced green fluorescent protein
      transgenic mice into the lesioned striatum. The injection of QA leads to an
      excitotoxic lesion with selective cell death of the medium sized spiny neurons,
      the same cells that are affected in Huntington's disease. In order to investigate
      the best timing of transplantation for the survival of donor cells, we
      transplanted the stem cells at 2, 7 and 14 days after injury. In addition, the
      influence of graft preparation prior to transplantation, i.e., intact
      neurospheres versus dissociated cell suspension on graft survival was
      investigated. By far the best survival was found with the combination of early
      transplantation (i.e., 2 days after QA-lesion) with the use of neurospheres
      instead of dissociated cell suspension. This might be due to the different states
      of host's astrocytic and microglia activation which we found to be moderate at 2,
      but pronounced at 7 and 14 days after QA-lesion. We also investigated brain
      derived neurotrophic factor (BDNF)-expression in the striatum after QA-lesion and
      found no significant change in BDNF protein-level. We conclude that already the
      method of graft preparation of NSCs for transplantation, as well as the timing of
      the transplantation procedure strongly affects the survival of the donor cells
      when grafted into the QA-lesioned striatum of adult mice.

PMID- 17013621
TI  - The role of genetic diversity in nest cooling in a wild honey bee, Apis florea.
AB  - Simulation studies of the task threshold model for task allocation in social
      insect colonies suggest that nest temperature homeostasis is enhanced if workers
      have slightly different thresholds for engaging in tasks related to nest
      thermoregulation. Genetic variance in task thresholds is one way a distribution
      of task thresholds can be generated. Apis mellifera colonies with large genetic
      diversity are able to maintain more stable brood nest temperatures than colonies
      that are genetically uniform. If this phenomenon is generalizable to other
      species, we would predict that patrilines should vary in the threshold in which
      they engage in thermoregulatory tasks. We exposed A. florea colonies to different
      temperatures experimentally, and retrieved fanning workers at these different
      temperatures. In many cases we found statistically significant differences in the
      proportion of fanning workers of different patrilines at different experimental
      temperatures. This suggests that genetically different workers have different
      thresholds for performing the thermoregulatory task of fanning. We suggest,
      therefore, that genetically based variance in task threshold is a widespread
      phenomenon in the genus Apis.

PMID- 17013622
TI  - Hybrid and multiscale modelling.

PMID- 17013623
TI  - Linked selected and neutral loci in heterogeneous environments.
AB  - We analyze a system of ordinary differential equations modeling haplotype
      frequencies at a physically linked pair of loci, one selected and one neutral, in
      a population consisting of two demes with divergent selection regimes. The system
      is singularly perturbed, with the migration rate m between the demes serving as a
      small parameter. We use geometric singular perturbation theory to show that when
      m is sufficiently small, each solution not initially fixed for the same selected
      allele in both demes approaches one of a 1-dimensional continuum of equilibria.
      We then obtain asymptotic expansions of the solutions and show their validity on
      arbitrarily long finite time intervals. From these expansions we obtain formulas
      for the transient dynamics of F(ST) (a measure of population structure) at both
      loci, as well as for the rate of genotyping error if the allelic state at the
      selected locus is inferred from that at the neutral (marker) locus. We examine
      two cases in detail, one modeling two populations in secondary contact after a
      period of evolution in allopatry, and the other modeling the origination and
      spread of a resistance allele.

PMID- 17013624
TI  - Rectal duplication cyst: a combined abdominal and endoanal operative approach.
AB  - Rectal duplication cysts are rare, comprising <5% of all gastrointestinal
      duplications. Early excision is the treatment of choice and a number of surgical
      approaches have been described. We present a 3-week-old infant with a 3 cm cyst
      that was excised using a previously unreported combined abdominal and endoanal
      approach.

PMID- 17013626
TI  - Torsion of an indirect hernia sac within a hydrocele causing acute scrotum: case
      report and review of the literature.
AB  - We report a case of acute scrotum in a 2-year-old child caused by torsion of an
      indirect hernia sac within a hydrocele. This is an extremely rare cause of acute
      scrotal swelling and pain in the pediatric population, with this case
      representing only the eighth instance reported in the literature. Despite the
      scarcity with which this diagnosis has been encountered, clinicians should
      include torsion of an indirect hernia sac on the differential diagnosis for acute
      scrotum in a child.

PMID- 17013625
TI  - Less is best? The impact of urokinase as the first line management of empyema
      thoracis.
AB  - To assess the impact of intrapleural urokinase and small tube thoracostomy on the
      management of childhood empyema thoracis. The study population included 38
      children presenting consecutively to a regional surgical unit with empyema
      thoracis from January 2001 to December 2003. Children with malignancy,
      immunodeficiency and complex intercurrent illness were excluded. Primary outcome
      variables were the need for second intervention and duration of stay, with other
      variables including duration of antibiotics, serial CRP and amelioration of
      pyrexia. Interventions were: tube thoracostomy (16-20 Fr) alone (n=2), tube
      thoracostomy (6-10 Fr)+urokinase (n=17), thoracoscopy (tube: 20-24 Fr) (n=9),
      thoracotomy (tube: 16-24 Fr) (n=10). There were no differences in age, weight or
      length of prodromal symptoms, between treatment groups. There were no differences
      in primary outcome variables, although no child undergoing thoracotomy required
      further intervention. The duration of intravenous antibiotics was similar in all
      groups. Amelioration of pyrexia was more rapid in children undergoing
      thoracotomy. There were no differences seen with regard to decline in CRP level.
      Small tube thoracostomy and intrapleural urokinase had a similar outcome to more
      invasive therapies such as thoracotomy or thoracoscopy thereby supporting the
      evidence base for urokinase and tube drainage as first line intervention.

PMID- 17013627
TI  - Endoscopic treatment of antrochoanal polyps.
AB  - The antrochoanal polyp (Killian polyp) is an infrequent, benign neoplasm, which
      arises from the maxillary sinus to reach the ipsilateral choana. The treatment of
      this disease is essentially surgical, by means of a wide antrostomy. The aim of
      the study was to compare the results obtained on 23 consecutive cases of
      antrochoanal polyps endoscopically treated between February 1997 and January 2000
      with those reported in the literature, with particular regard to the surgical
      technique adopted, the histological features, the patterns of its development and
      the clinical outcomes. The histology revealed in most of the cases a cystic
      aspect surrounded by edematous stroma. In all cases the polyp emerged from the
      middle meatus, mostly starting from the upper-lateral (zygomatic) wall of the
      antrum. All patients were endoscopically followed-up for an average period of 39
      months (17-61). We observed two recurrences, both in pediatric cases who
      evidently underwent an incomplete surgical removal of antral mucosa at its
      inferior aspect, probably due to the fear of damaging the teeth buds. We did not
      observe any postsurgical complication. Our data indicate the endoscopic middle
      meatal antrostomy as the optimal approach, also for the revision cases and in
      children.

PMID- 17013628
TI  - Spindle cell rhabdomyosarcoma in adults: clinicopathological and
      immunohistochemical analysis of seven new cases.
AB  - Rhabdomyosarcoma (RMS) is currently classified into embryonal RMS, including its
      botryoid and spindle cell variants, alveolar RMS, including a solid variant, and
      pleomorphic RMS. In children and adolescents embryonal RMS occurs in a younger
      age group than alveolar RMS, and pleomorphic RMS is almost always seen in older
      adults. Most recently rare spindle cell and sclerosing, pseudovascular RMS have
      been reported in adults as well. We analysed the clinicopathological and
      immunohistochemical features of seven new cases of spindle cell RMS arising in
      adult patients. Five patients were male and two were female and the age of the
      patients ranged from 38 to 76 years. Four neoplasms arose on the lower
      extremities and one case each on the forearm, the lateral aspect of the neck and
      the penis. Five neoplasms were completely excised, in one incompletely excised
      neoplasm additional chemotherapy was given, and in one patient a biopsy was done
      only so far. All neoplasms arose in subcutaneous and deep soft tissues with
      dermal involvement in one case, and the size of the neoplasms ranged from 4 to 19
      cm in largest diameter. Histologically, a plump or diffuse infiltration was seen,
      and all neoplasms were mainly composed of cellular bands and fascicles of
      atypical spindle-shaped tumour cells containing enlarged and atypical nuclei
      associated with a variable number of rhabdomyoblasts. In addition, focal areas
      reminiscent of sclerosing, pseudovascular RMS were noted in three cases, and in
      two cases each small solid areas with pleomorphic tumour cells as well as
      scattered round tumour cells were present. Proliferative activity ranged from 1
      to 60 mitoses in 10 high-power fields and tumour necrosis was evident in four
      cases. Immunohistochemically, all neoplasms tested stained variably positive for
      desmin, myf-4, WT1 and CD 99, whereas fast myosin was positive in only two out of
      seven cases. In addition, five out of seven cases tested stained focally positive
      for alpha-smooth muscle actin. The remaining antibodies (h-caldesmon, S-100
      protein, CD 34, pancytokeratin and epithelial membrane antigen) were all
      negative. Follow-up information was available in five patients (range from 10 to
      48 months) and revealed lung metastases in two patients who died of disease
      within a short period. In summary, spindle cell rhabdomyosarcoma represents a
      rare neoplasm in adulthood characterized clinically by a rather poor prognosis,
      and shows a broad morphological spectrum including most likely the sclerosing,
      pseudovascular variant. Immunohistochemically, tumour cells in RMS stain
      positively for CD 99 and WT1 as well, which is of importance in the differential
      diagnosis to other mesenchymal neoplasms, whereas fast myosin does not represent
      a reliable marker for RMS in adults.

PMID- 17013629
TI  - Expression of endothelin 1 and its angiogenic role in meningiomas.
AB  - Meningiomas are one of the most frequent central nervous system tumours. Although
      slow-growing at times, they continue to be a cause of morbidity and mortality.
      The endothelin (ET) family consists of three isoforms: ET-1 is the most abundant
      one. ET-1 may be involved in meningioma tumourigenesis in concert with other
      growth factors, in particular with angiogenic agents. We analysed ET-1 expression
      by immunohistochemistry and its activating system by reverse-transcription
      polymerase chain reaction in 56 cases of meningioma. We found an association
      between high-grade meningiomas and high ET-1 expression levels (p=0.002).
      Moreover, we evaluated the potential angiogenic role of ET-1, finding an elevated
      microvessel count in tumours with high ET expression levels (p=0.004). ET-1 may
      contribute to meningioma growth by inducing formation of new blood vessels. The
      finding that ET-1 expression positively correlates with vascular endothelial
      growth factor (VEGF) expression in meningiomas (p=0.03) also supports the
      hypothesized modulating effect of ET-1 on angiogenesis. Thus, the influence of
      the ET system on the progression of meningiomas may occur through stimulation of
      VEGF. The association of ET-1 and meningioma represents a potential area for
      therapeutic intervention with selective ET inhibitors. Additional clinical
      studies will be needed before inhibitors can be incorporated in clinical
      practice.

PMID- 17013630
TI  - Density functional study of closed-shell attraction on X(ML)3 + (X = O, S, Se; M
      = Au, Ag, Cu) systems.
AB  - With the help of quantum mechanical calculations, we have examined the series of
      central system X(ML)(3) (+)(X = O, S, Se; M = Au, Ag, Cu). Using a scalar
      relativistic density functional approach, we studied the geometry structures,
      Mulliken populations and charges of the systems. Structure parameters of the
      experimental systems are reproduced well with Xalpha method. The metallophilic
      interaction energy is analyzed and decomposed. For the systems with different
      central atoms and different metal atoms, the nature of the metallophilic
      attraction interaction is analyzed.

PMID- 17013631
TI  - An overview of halogen bonding.
AB  - Halogen bonding (XB) is a type of noncovalent interaction between a halogen atom
      X in one molecule and a negative site in another. X can be chlorine, bromine or
      iodine. The strength of the interaction increases in the order Cl<Br<I. After a
      brief review of experimental evidence relating to halogen bonding, we present an
      explanation for its occurrence in terms of a region of positive electrostatic
      potential that is present on the outermost portions of some covalently-bonded
      halogen atoms. The existence and magnitude of this positive region, which we call
      the sigma-hole, depends upon the relative electron-attracting powers of X and the
      remainder of its molecule, as well as the degree of sp hybridization of the s
      unshared electrons of X. The high electronegativity of fluorine and its tendency
      to undergo significant sp hybridization account for its failure to halogen bond.
      Some computed XB interaction energies are presented and discussed. Mention is
      also made of the importance of halogen bonding in biological systems and
      processes, and in crystal engineering.

PMID- 17013632
TI  - Density functional study of isoguanine tetrad and pentad sandwich complexes with
      alkali metal ions.
AB  - Isoguanine tetraplexes and pentaplexes contain two or more stacked polyads with
      intercalating metal ions. We report here the results of a density functional
      study of sandwiched isoguanine tetrad and pentad complexes consisting of two
      polyads with Na(+), K(+) and Rb(+) ions at the B3LYP level. In comparison to
      single polyad metal ion complexes, there is a trend towards increased non
      planarity of the polyads in the sandwich complexes. In general, the pentad
      sandwiches have relatively planar polyad structures, whereas the tetrad complexes
      contain highly non-planar polyad building blocks. As in other sandwich complexes
      and in metal ion complexes with single polyads, the metal ion-base interaction
      energy plays an essential role. In iG sandwich structures, this interaction
      energy is slightly larger than in the corresponding guanine sandwich complexes.
      Because the base-base interaction energy is even more increased in passing from
      guanine to isoguanine, the isoguanine sandwiches are thus far the only examples
      where the base-base interaction energy is larger than the base-metal ion
      interaction energy. Stacking interactions have been studied in smaller models
      consisting of two bases, retaining the geometry from the complete complex
      structures. From the data obtained at the B3LYP and BH&H levels and with Moller
      Plesset perturbation theory, one can conclude that the B3LYP method overestimates
      the repulsion in stacked base dimers. For the complexes studied in this work,
      this is only of minor importance because the direct inter-tetrad or inter-pentad
      interaction is supplemented by a strong metal ion-base interaction. Using a
      microsolvation model, the metal ion preference K(+) approximately Rb(+) > Na(+)
      is found for tetrad complexes. On the other hand, for pentads the ordering is
      Rb(+) > K(+) > Na(+). In the latter case experimental data are available that
      agree with this prediction.

PMID- 17013633
TI  - Thrombin inhibitors with novel P1 binding pocket functionality: free energy of
      binding analysis.
AB  - The high incidence of thrombembolic diseases justifies the development of new
      antithrombotics. The search for a direct inhibitor has resulted in the synthesis
      of a considerable number of low molecular weight molecules that inhibit human
      alpha-thrombin potently. However, efforts to develop an orally active drug remain
      in progress as the most active inhibitors with a highly basic P1 moiety exhibit
      an unsatisfactory bioavailability profile. In our previous work we solved several
      X-ray structures of human alpha-thrombin in complexes with (1) novel bicyclic
      arginine mimetics attached to the glycylproline amide and pyridinone acetamide
      scaffold and (2) inhibitors with a novel aza scaffold and with charged or neutral
      P1 moieties. In the present contribution, we correlate the structures of the
      complex between these inhibitors and the protein with the calculated free energy
      of binding. The energy of solvation was calculated using the Poisson-Boltzmann
      approach. In particular, the requirements for successful recognition of an
      inhibitor at the protein's active site pocket S1 are discussed.

PMID- 17013634
TI  - Evidence for a tellurite-dependent generation of reactive oxygen species and
      absence of a tellurite-mediated adaptive response to oxidative stress in cells of
      Pseudomonas pseudoalcaligenes KF707.
AB  - Tellurite (TeO3(2-)) is the most toxic and soluble oxyanion among tellurium (Te)
      compounds. The effects of the metalloid anion on the oxidative stress response of
      the obligate aerobe Pseudomonas pseudoalcaligenes KF707 were investigated. Cells
      treated with sub-lethal concentrations of TeO3(2-) showed neither adaptation to
      it nor cross-protection against oxidants such as 1,1'-4,4'-bipyridinium
      dichloride (paraquat, PQ2+), diazenedicarboxylic acid bis-N,N-dimethylamide
      (diamide), tert-butyl hydroperoxide (tBH) and hydrogen peroxide (H2O2). Notably,
      TeO3(2-) exerted a synergic effect on the toxicity of these latter oxidants.
      Tellurite was shown to decrease the cellular content of reduced thiols (RSH) with
      a consequent increase in the production of reactive oxygen species (ROS) and
      stimulation of the superoxide dismutase (SOD) activity. However, since the time
      course of ROS production by TeO3(2) (t1/2 > 30 min) was much slower than that
      with PQ2+ and/or diamide (t1/2 <or= 10 min), in the former case the SOD activity
      was poorly activated. We conclude that in P. pseudoalcaligenes KF707 cells: (1)
      the TeO3(2-) acts as a pro-oxidant by stimulating ROS production; (2) the release
      of superoxide oxyanions is directly linked to the mechanism of toxicity; (3)
      TeO3(2-) is unable to induce an adaptive response to oxidative stress.

PMID- 17013635
TI  - Impaired recognition of fear facial expressions in 5-HTTLPR S-polymorphism
      carriers following tryptophan depletion.
AB  - RATIONALE: Genotype at the 5' promoter region (5-HTTLPR) of the serotonin
      transporter has been implicated in moderating the effects of acute tryptophan
      depletion on neurocognitive functioning. Acute tryptophan depletion has been
      associated with the processing of fear-relevant cues, such as emotional
      expressions, but the effect of genotype at the 5-HTTLPR has not been assessed.
      OBJECTIVE: The present study investigated the effects of acute tryptophan
      depletion on the recognition of standardized facial expressions of emotions in
      healthy volunteers classified as ll homozygotes or s carriers. MATERIALS AND
      METHODS: A double-blind between-groups design was used with volunteers randomly
      selected to ingest capsules containing an amino acid mixture specifically lacking
      tryptophan, or placebo capsules containing lactose. 5 h after capsule ingestion,
      subjects were required to identify anger, disgust, fear, happiness, sadness, and
      surprise expressions that progressed from neutral to each full emotional
      expression in 5% steps. RESULTS: Tryptophan depletion significantly impaired the
      recognition of fearful facial expressions in s carriers but not ll homozygotes.
      This impairment was specific to fear expressions. No significant differences in
      the recognition of other expressions were found. Free tryptophan levels were
      correlated with fear recognition in s carriers but not ll homozygotes.
      CONCLUSIONS: The effects of acute tryptophan depletion on the processing of
      emotional expressions varies as a function of genotype at the 5-HTTLPR. Depletion
      impairs the recognition of fear in s carriers but not ll homozygotes. This
      finding reinforces the importance of considering genotype when assessing the
      behavioral effects of pharmacologic modulation.

PMID- 17013636
TI  - The effects of tea on psychophysiological stress responsivity and post-stress
      recovery: a randomised double-blind trial.
AB  - RATIONALE: Tea has anecdotally been associated with stress relief, but this has
      seldom been tested scientifically. OBJECTIVES: To investigate the effects of 6
      weeks of black tea consumption, compared with matched placebo, on subjective,
      cardiovascular, cortisol and platelet responses to acute stress, in a parallel
      group double-blind randomised design. MATERIALS AND METHODS: Seventy-five healthy
      nonsmoking men were withdrawn from tea, coffee and caffeinated beverages for a 4
      week wash-out phase during which they drank four cups per day of a caffeinated
      placebo. A pretreatment laboratory test session was carried out, followed by
      either placebo (n = 38) or active tea treatment (n = 37) for 6 weeks, then, a
      final test session. Cardiovascular measures were obtained before, during and
      after two challenging behavioural tasks, while cortisol, platelet and subjective
      measures were assessed before and after tasks. RESULTS: The tasks induced
      substantial increases in blood pressure, heart rate and subjective stress
      ratings, but responses did not differ between tea and placebo treatments.
      Platelet activation (assessed using flow cytometry) was lower following tea than
      placebo treatment in both baseline and post-stress samples (P < 0.005). The
      active tea group also showed lower post-task cortisol levels compared with
      placebo (P = 0.032), and a relative increase in subjective relaxation during the
      post-task recovery period (P = 0.036). CONCLUSIONS: Compared with placebo, 6
      weeks of tea consumption leads to lower post-stress cortisol and greater
      subjective relaxation, together with reduced platelet activation. Black tea may
      have health benefits in part by aiding stress recovery.

PMID- 17013637
TI  - Effects associated with double-blind omission of buprenorphine/naloxone over a 98
      h period.
AB  - RATIONALE: Buprenorphine has a long duration of action that allows less than
      daily dosing for opioid dependence, but pharmacologic characterization of
      buprenorphine's duration of effects over multiple days is incomplete. OBJECTIVES:
      This study assessed opioid blockade and spontaneous withdrawal effects of
      buprenorphine/naloxone (B/N) over a 98-h period. MATERIALS AND METHODS:
      Residential opioid-dependent volunteers (n = 8) were maintained, in randomized
      sequence, on each of three different daily sublingual B/N doses (8/2, 16/4, 32/8
      mg). After 2 weeks on each maintenance dose, participants underwent challenge
      sessions on each weekday for 1 week. Challenges consisted of within-session,
      ascending dose administration of IM hydromorphone (H: 0, 6, and 12 mg). During
      that week, active B/N dose was given only on Monday; double-blind placebo was
      administered on the remaining weekdays. Thus, these sessions assessed the extent
      of both opioid blockade and spontaneous withdrawal at 2, 26, 50, 74, and 98 h
      after the last active B/N dose. RESULTS: All three maintenance doses provided
      substantial but incomplete blockade against opioid agonist effects for 98 h. The
      extent of blockade diminished steadily but modestly over this time and did not
      differ as a function of B/N maintenance dose. In general, participants did not
      report marked spontaneous opioid withdrawal, although mild withdrawal effects
      were observed as time since the last active B/N dose increased. However,
      withdrawal did not differ as a function of B/N maintenance dose. CONCLUSIONS:
      These findings suggest that B/N doses greater than 8/2 mg provide minimal
      incremental value in terms of opioid blockade and withdrawal suppression.

PMID- 17013638
TI  - The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor
      activity and prepulse inhibition in rats.
AB  - RATIONALE: The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is
      structurally similar to other indoleamine hallucinogens such as LSD. The present
      study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern
      Monitor (BPM), which enables analyses of patterns of locomotor activity and
      exploration, and the prepulse inhibition of startle (PPI) paradigm. OBJECTIVES: A
      series of interaction studies using the serotonin (5-HT)(1A) antagonist WAY
      100635 (1.0 mg/kg), the 5-HT(2A) antagonist M100907 (1.0 mg/kg), and the 5-HT(2C)
      antagonist SER-082 (0.5 mg/kg) were performed to assess the respective
      contributions of these receptors to the behavioral effects of 5-MeO-DMT (0.01,
      0.1, and 1.0 mg/kg) in the BPM and PPI paradigms. RESULTS: 5-MeO-DMT decreased
      locomotor activity, investigatory behavior, the time spent in the center of the
      BPM chamber, and disrupted PPI. All of these effects were antagonized by WAY
      100635 pretreatment. M100907 pretreatment failed to attenuate any of these
      effects, while SER-082 pretreatment only antagonized the PPI disruption produced
      by 5-MeO-DMT. CONCLUSIONS: While the prevailing view was that the activation of 5
      HT(2) receptors is solely responsible for hallucinogenic drug effects, these
      results support a role for 5-HT(1A) receptors in the effects of the indoleamine
      hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.

PMID- 17013639
TI  - Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis
      rats.
AB  - RATIONALE: Application of the Fischer-Lewis genetic model of drug abuse to the
      study of alcohol's motivational properties has been limited. OBJECTIVES: To
      assess the aversive and rewarding effects of ethanol in Fischer and Lewis rats.
      MATERIALS AND METHODS: Fischer and Lewis rats underwent a four-trial combined
      conditioned taste aversion/conditioned place preference procedure (CTA/CPP; 0, 1,
      1.25, or 1.5 g/kg IP ethanol). Others received 0, 1, or 1.5 g/kg followed by tail
      blood sampling at 15-, 60- and 180-min post-injection. In additional groups,
      hypothermia to 0, 1.5, and 3 g/kg was assessed before and 30- and 60-min post
      injection. RESULTS: All alcohol-treated groups except low-dose Lewis acquired CTA
      after one trial. Fischer rats developed stronger CTAs than Lewis at 1.25 and 1.5
      g/kg. Ethanol-induced reward in taste or place conditioning was not evident in
      either strain. Lewis animals showed overall higher peak blood alcohol
      concentrations, but hypothermia did not vary by strain. CONCLUSION: Compared to
      Fischer, Lewis rats are less sensitive to alcohol's aversive effects as assessed
      in the CTA paradigm. The behavioral differences observed are not due to
      hypothermia, but pharmacokinetic differences may contribute. These data
      underscore the importance of genetic factors and the aversive effects of initial
      drug exposures in modeling vulnerability to abuse. In addition to its application
      with other drugs, the Fischer-Lewis model may be useful for investigating the
      biobehavioral bases of alcohol abuse.

PMID- 17013640
TI  - Modeling the effect of alcohol on smoking lapse behavior.
AB  - OBJECTIVE: The primary aim of this project was to examine the role of alcohol use
      in smoking lapse behavior, as alcohol consumption is a known risk factor for poor
      smoking cessation outcomes. MATERIALS AND METHODS: We have developed a novel
      human laboratory model to examine two primary aspects of alcohol-mediated tobacco
      relapse: (1) Does alcohol facilitate the initiation of the first cigarette? (2)
      Once the first cigarette is initiated, does alcohol facilitate subsequent
      smoking? Using a within-subject design, 16 daily smokers who were also heavy
      social drinkers received a priming drink (0.03 g/dl or taste-masked placebo) and
      then had the option of initiating a tobacco self-administration session or
      delaying initiation by 5-min increments for up to 50 min in exchange for monetary
      reinforcement. Subsequently, the tobacco self-administration session consisted of
      a 1-h period in which subjects could choose to smoke their preferred brand of
      cigarettes using a smoking topography system or receive monetary reinforcement
      for cigarettes not smoked. Alcohol craving, tobacco craving, subjective
      reactivity to alcohol, and nicotine withdrawal were assessed as secondary
      outcomes. RESULTS: Results demonstrated that after consuming the alcohol
      beverage, subjects were less able to resist the first cigarette and initiated
      their smoking sessions sooner, and smoked more cigarettes compared to the placebo
      beverage. These findings have implications for smoking cessation in alcohol
      drinkers and model development to assess smoking lapse behavior.

PMID- 17013641
TI  - Facet joint violation during pedicle screw insertion: a cadaveric study of the
      adult lumbosacral spine comparing the two pedicle screw insertion techniques.
AB  - This article analyses the incidence of facet joint violation by pedicle screws
      inserted via the two most commonly used techniques, intersection and mammillary.
      Pedicle screws were inserted on each side of fresh-frozen human cadevaric
      specimen lumbosacral spines using the two techniques. All facet joints which were
      violated were found to be on the right side, where the mamillary process
      technique was employed. The incidence of facet joint violation was higher in the
      mammillary technique, which was statistically significant. The intersection
      technique appears to be safer than the mamillary with respect to violation of the
      adjacent superior facet joint.

PMID- 17013642
TI  - Massive allografts in tumour surgery.
AB  - We offer our personal experience of the use of massive bone allografts after
      tumour resection. We demonstrate the long-term results from 71 patients (72
      allografts) operated on between 1961 and 1990. The long-term survival rate in
      osteoarticular and intercalary grafts is around 60%. Fractures of the graft can
      be salvaged in most cases. Infection leads to the removal of the graft in almost
      all cases. Factors influencing the survival, remodelling and complications of the
      grafts are discussed. The regime of cryopreservation, fixation and loading of the
      graft influence these factors, as do the use of autologous bone chips around the
      allograft-host junction and the application of chemotherapy or radiation.
      Fracture of the graft can be salvaged in most cases, as opposed to infection
      which remains the most severe complication and can occur at any time. Even with
      the improvement of tumour endoprostheses, the use of allografts remains an
      option, especially in young patients.

PMID- 17013644
TI  - Combination index of soluble transferrin receptor and mean corpuscular hemoglobin
      for evaluating iron deficiency in end-stage renal disease.

PMID- 17013643
TI  - Giant cell tumour of bone: morphological, biological and histogenetical aspects.
AB  - The giant cell tumour of bone (GCT) is a locally aggressive intraosseous neoplasm
      of obscure biological behaviour. Although well defined in clinical, radiological
      and histological terms, detailed information on its biological development is
      still relatively incomplete. The tumoral tissue consists of three cell types--the
      neoplastic giant cell tumour stromal cells (GCTSC), representing the
      proliferative fraction, secondarily recruited mononuclear histiocytic cells
      (MNHC) and multinuclear giant cells (MNGC). These cellular components interact
      together with factors that have a role in regulating osteoclast function in
      normal bone tissue (e.g. RANK, RANKL, OPG, M-CSF). Recent publications suggest
      that the neoplastic stromal cells express differentiation features of mesenchymal
      stem cells. Further research of the pathogenesis of GCT as well as the complex
      interactions of its cellular populations may provide the knowledge necessary for
      developing approaches for a biological-based therapy of this neoplasm.

PMID- 17013645
TI  - Effect of zoledronic acid on markers of bone turnover and mineral density in
      osteoporotic patients with beta-thalassaemia.
AB  - Osteoporosis has emerged as an important cause of morbidity in patients with
      thalassemia major. Studies regarding the efficacy of bisphosphonates in
      thalassemia-induced osteoporosis have yielded conflicting results. We performed
      this prospective study to evaluate the efficacy of zoledronic acid in
      osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg
      zoledronic acid intravenously every 3 months for a total of four doses. Twenty
      age- and sex-matched healthy blood donors served as controls. Before each
      infusion and 3 months after the last infusion, we determined serum levels of
      osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen
      (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral
      density (BMD) of the lumbar spine was measured at baseline and after the
      treatment's completion. At baseline, OPG did not differ significantly between
      patients and controls (p=0.2), NTX were higher in patients although not
      significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1
      levels significantly lower in patients than in controls (p<0.001 and p<0.006,
      respectively). Zoledronic acid administration resulted in a significant decrease
      in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a
      significant increase in OPG and BMD (p<0.05 for both comparisons). The change in
      NTX, osteocalcin and IGF-1 became significant as early as 3 months after the
      first administration of zoledronic acid, while the change in OPG reached
      significance only after three infusions. Our study supports the effectiveness of
      bisphosphonates in the treatment of thalassemia-induced osteoporosis.

PMID- 17013646
TI  - Frequency of the hemochromatosis gene (HFE) 282C-->Y, 63H-->D, and 65S-->C
      mutations in a general Mediterranean population from Tarragona, Spain.
AB  - Three mutations have recently been detected in the hereditary hemochromatosis HFE
      gene (282C-->Y, 63H-->D, and 65S-->C). To determine their prevalence in a
      northeastern Spanish Mediterranean population, we studied 812 subjects between 18
      and 75 years of age, randomly selected from the electoral roll of three villages.
      There were no homozygotes for the 282C-->Y or S65D mutations in this sample. For
      the 63H-->D mutation, 4.8% were homozygotes; 4.3, 32.3, and 2% were heterozygotes
      for the 282C-->Y, 63H-->D, and 65S-->C mutations, respectively. The prevalence of
      compound heterozygotes was 2% for 282C-->Y/63H-->D and 0.6% for 63H-->D /65S-->C.
      We found no significant differences between men and women. In conclusion, 46% of
      this Mediterranean population of Spain are carriers of at least one of the three
      mutations that can increase iron absorption.

PMID- 17013647
TI  - Molecular epidemiology of Trichinella spp. in three Baltic countries: Lithuania,
      Latvia, and Estonia.
AB  - Meat of domestic pigs and wild boars has been the significant source of emerged
      human trichinellosis in Lithuania, Latvia, and Estonia over the past two decades.
      However, there is very little known on the occurrence of Trichinella spp. in main
      wildlife reservoirs and its transmission in domestic and sylvatic cycles in these
      countries. The present study demonstrated considerably higher endemicity of
      Trichinella spp. in main sylvatic reservoirs (28.9-42% in foxes (Vulpes vulpes)
      and raccoon dogs (Nyctereutes procyonoides) in all three countries than
      previously reported. Molecular identification of Trichinella larvae from more
      than 500 sylvatic and domestic animals revealed four Trichinella species
      (Trichinella spiralis, Trichinella britovi, Trichinella nativa, and Trichinella
      pseudospiralis) sympatric in a relatively small area and several as the first
      records for the respective countries. The nonencapsulating T. pseudospiralis is
      found for the first time in the Eastern Europe. Sylvatic T. britovi was found in
      domestic pigs in Lithuania and Latvia (16 and 57.1%, respectively) and only in
      these countries, domestic T. spiralis was detected in sylvatic animals in areas
      where domestic trichinellosis was registered. The study suggests that
      transmission of Trichinella between domestic and sylvatic cycles in Lithuania and
      Latvia is favored by improper human behavior, e.g., pig and slaughter waste
      management.

PMID- 17013648
TI  - Leishmania major: common antigen responsible for induction of delayed-type
      hypersensitivity response in guinea pigs.
AB  - The cellular response to Leishmania major (L. major) was evaluated in vivo by
      delayed-type hypersensitivity (DTH) skin test reaction using leishmanin as
      antigen. Our previous study had shown the development of species-specific DTH
      reaction in sensitized guinea pigs by application of a single purified antigen
      from promastigotes and filtered culture supernatants of L. major. This study has
      shown that purified antigen is common in both stages of the life cycle and
      filtered culture supernatant of L. major. The common antigen was purified and
      analyzed from soluble Leishmania antigen (SLA) of amastigotes, promastigotes, and
      filtered culture supernatant of L. major by specific monoclonal antibody coupled
      to sepharose-4B. The purified antigen, which gave a single band of 56 kDa on
      sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE) electrophoresis, elicited
      DTH response in guinea pigs sensitized with L. major. It was almost of the same
      degree as that produced by whole SLA. These results show that DTH inducer antigen
      is present in both stages of the life cycle and filtered culture supernatant of
      L. major.

PMID- 17013649
TI  - In vitro screening of medicinal plant extracts for macrofilaricidal activity.
AB  - Methanolic extracts of 20 medicinal plants were screened at 1-10 mg/ml for in
      vitro macrofilaricidal activity by worm motility assay against adult Setaria
      digitata, the cattle filarial worm. Four plant extracts showed macrofilaricidal
      activity by worm motility at concentrations below 4 mg/ml and an incubation
      period of 100 min. Complete inhibition of worm motility and subsequent mortality
      was observed at 3, 2, 1 and 1 mg/ml, respectively, for Centratherum
      anthelminticum, Cedrus deodara, Sphaeranthus indicus and Ricinus communis. 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) reduction assay was
      carried out at 1 mg ml(-1) and 4-h incubation period, and the results showed that
      C. deodara, R. communis, S. indicus and C. anthelminticum exhibited 86.56, 72.39,
      61.20 and 43.15% inhibition respectively in formazan formation compared to the
      control.

PMID- 17013650
TI  - The effects of artemether-lumefantrine vs amodiaquine-sulfalene-pyrimethamine on
      the hepatomegaly associated with Plasmodium falciparum malaria in children.
AB  - An open randomized controlled study of artemether-lumefantrine (AL) and
      amodiaquine-sulfalene-pyrimethamine (ASP) for the treatment of uncomplicated
      Plasmodium falciparum malaria was carried out in 181 children. In 79 children,
      the hepatomegaly reduction ratios (HRR) and the speed of resolution of
      hepatomegaly, the hepatomegaly resolution rates (HRSR), were calculated and
      compared between the two treatment groups. HRR and HRSR were similar in the two
      treatment groups. HRSR was 71% and 62% in AL- and ASP-treated children,
      respectively, 14 days after commencing treatment. There was no significant
      correlation between HRR and parasite reduction ratio in the same patient. In
      children in whom parasitaemia cleared and hepatomegaly resolved within 14 days,
      recurrence of parasitaemia was associated with reoccurrence of hepatomegaly,
      suggesting that the propensity for recurrence of infection drives the malaria
      attributable hepatomegaly in children from this endemic area. Combination therapy
      may provide additional beneficial effects on pathophysiological processes and
      changes associated with falciparum malaria by rapid clearing of asexual
      parasitaemia and reducing the propensity for recurrence of infection.

PMID- 17013651
TI  - Detection of Giardia assemblage A in cats in Florence, Italy.
AB  - In the present study, the assemblage of Giardia isolates from stray and owned
      cats was investigated. Faeces were randomly collected from 27 cats, screened by
      microscopy and examined by molecular methods that included DNA extraction, small
      subunit rRNA gene amplification and DNA sequence analysis. Ten cats were found to
      be infected with Giardia and harbouring cysts belonging to the zoonotic
      assemblage A. The cat-specific assemblage F was not found. Such a high proportion
      of Giardia assemblage A in cats may pose for a different geographical
      distribution of assemblages in the world. These findings provide insights that
      may be useful to map the epidemiological risk of the infection worldwide, as this
      may be instrumental in safeguarding human health.

PMID- 17013652
TI  - Parasite field study in central Kentucky on thoroughbred foals (born in 2004)
      treated with pyrantel tartrate daily and other parasiticides periodically.
AB  - Foals (79), born in 2004 on three thoroughbred horse farms (C, M, and S) in
      central Kentucky, were fed pyrantel tartrate daily, beginning at about 3 months
      of age. In addition, other parasiticides [fenbendazole (FBZ), ivermectin (IVM)
      alone or with praziquantel (PRAZ), oxibendazole (OBZ), pyrantel pamoate (PRT),
      and moxidectin (MOX)] were given periodically. All treatments were administered
      by farm personnel. Over a 14-month period, from May 2004 to July 2005,
      collections (n=989) of feces were made from the foals for determination of
      presence of internal parasite eggs/oocysts by qualitative and/or quantitative
      methods. Conclusions on drug activity are based necessarily on considering the
      combined effect of pyrantel tartrate and the other compounds. For small
      strongyles, this was related to which specific additional compound was given.
      Based on the percentage of foals with strongyle-egg-positive feces and/or the
      level of eggs per gram of feces (EPG) counts for the foals after treatment, drug
      activity on small strongyles was highest to lowest for MOX, IVM and IVM/PRAZ,
      FBZ, OBZ, PRT, and FBZ (2x for 5 days). The macrocyclic lactones (MOX and IVM)
      were highly superior to the other compounds. Some of the strongyle counts were
      high (over 2,000), especially on one farm (S), during periods when foals received
      only pyrantel tartrate, but a few days after administration of therapeutic dose
      rates of the drugs IVM or MOX, they were negative or very low. Ascarid eggs were
      present in feces of three foals after treatment with a combination of IVM and
      PRAZ. The qualitative method was more efficient than the quantitative method in
      detection of ascarid and strongyle eggs in the feces. Prevalence of eggs of
      ascarids (Parascaris equorum) was low (0, 4, and 31%), of strongyles high (80,
      100, and 100%), of Strongyloides westeri very low (only one infected foal), and
      oocysts of Eimeria leuckarti medium to high (36, 41, and 85%) for the three
      farms, C, M, and S, respectively. It is uncertain whether the low ascarid
      prevalence was from activity of pyrantel tartrate and/or the other drugs or to a
      limited source of infective eggs.

PMID- 17013653
TI  - Acanthamoeba keratitis due to Acanthamoeba genotype T4 in a non-contact-lens
      wearer in Turkey.
AB  - An otherwise healthy 22-year-old man presented with Acanthamoeba keratitis (AK)
      in the right eye. He was not a contact lens wearer and had no history of corneal
      trauma. The Acanthamoeba strain isolated from a corneal scraping was identified
      as morphological group II and genotype T4. Three more Acanthamoeba strains
      isolated from sites of possible human contact with acanthamoebae in the same
      geographical region, including a lens storage case, tap water and soil, were
      subjected to morphological and molecular biological identification. Whereas the
      strain from tap water also exhibited genotype T4, the two other isolates were
      identified as morphological group I and genotype T9. To the best of our
      knowledge, this is the first study identifying an AK-causing Acanthamoeba strain
      in Turkey and the first isolation of genotype T9 in this country.

PMID- 17013654
TI  - The advantages of submandibular gland resection in anterior retropharyngeal
      approach to the upper cervical spine.
AB  - Anterior surgery to the upper cervical spine, although rare, several successful
      approaches were described in the literature. To avoid the risks and limitations
      of transoral approach, the anterior retropharyngeal approach was developed. In
      this study, we describe our experience with anterior retropharyngeal approach to
      the upper cervical spine and discuss the significance of resecting the
      submandibular gland. From July 2001 to July 2004, we performed six anterior
      prevascular retropharyngeal approaches to the upper cervical spine. The series
      included five males and one female, ranging in age from 26 to 60 years (mean =
      46). All six patients were intubated with nasotracheal cannula. The submandibular
      gland was mobilized and removed in all patients allowing adequate exposure of the
      arch of C1, C2, and C3 vertebral bodies. The anterior retropharyngeal approach
      permitted an adequate access to anteriorly situated lesions from C1 to C3 in all
      six patients, without the risks and limitations of transmucosal surgery. This
      approach allowed us to perform decompression of the spinal cord and
      reconstruction of the anterior column of the spine with bone graft and internal
      fixation. Careful removal of the submandibular gland provided better
      visualization of the arch of C1 and C2. No facial nerve palsy was seen in any of
      the six patients. Anterior retropharyngeal approach to the upper cervical spine
      combined with removal of the submandibular gland permits exposure of the anterior
      spine similar to that obtained by the transmucosal route, and provides a safe
      simultaneous arthrodesis and instrumentation during the primary surgical
      procedure without the potential contamination of the oropharyngeal cavity.
      Removal of the submandibular gland allows better exposure with less retraction
      and thus avoids severe injury to the mandibular branch of the facial nerve.

PMID- 17013655
TI  - Back posture education in elementary schoolchildren: a 2-year follow-up study.
AB  - Within the scope of primary prevention regarding back functioning in children,
      research on the stability of intervention effects is indispensable. Along this
      line, the transition from childhood to adolescence is an important phase to
      evaluate the potential stability of intervention effects because of the typically
      mechanical and psychological demands related to adolescence. The main aim of the
      current study was to investigate the effects of a back education program at 2
      year follow-up, in youngsters aged 13-14 years, on back posture knowledge, fear
      avoidance beliefs and self-reported pain. An additional purpose was to evaluate
      which aspects of postural behavior were integrated in youngsters' lifestyles. At
      2-year follow-up, the study sample included 94 secondary schoolchildren in the
      intervention group (mean age 13.3 +/- 0.8 years) and 101 controls (mean age 13.2
      +/- 0.7 years). The back posture program that had been implemented for two school
      years consisted of back education and the stimulation of postural dynamism in the
      class through support and environmental changes. A questionnaire was completed
      comparable to the pretest, posttest and follow-up evaluations. The current study
      demonstrated at 2-year follow-up stability of the improved general (F = 1.590,
      ns) and specific (F = 0.049, ns) back posture knowledge in children who had
      received early back posture education. Back posture education did not result in
      increased fear-avoidance beliefs (F = 1.163, ns) or mounting back and/or neck
      pain reports (F = 0.001, ns). Based on self-reports for postural behavior,
      youngsters who had received the back posture program in the elementary school
      curriculum integrated crucial sitting and lifting principles conform to
      biomechanical favorable postural behavior. The steady intervention effects 2-year
      post-intervention demonstrated that intensive back posture education through the
      elementary school curriculum is effective till adolescence. Future research on
      the impact of early school-based back posture promotion in relation to the
      integration of back posture principles according to a biomechanical favorable
      lifestyle and back pain prevalence later in life is essential.

PMID- 17013656
TI  - A systematic review of the diagnostic accuracy of provocative tests of the neck
      for diagnosing cervical radiculopathy.
AB  - Clinical provocative tests of the neck, which position the neck and arm inorder
      to aggravate or relieve arm symptoms, are commonly used in clinical practice in
      patients with a suspected cervical radiculopathy. Their diagnostic accuracy,
      however, has never been examined in a systematic review. A comprehensive search
      was conducted in order to identify all possible studies fulfilling the inclusion
      criteria. A study was included if: (1) any provocative test of the neck for
      diagnosing cervical radiculopathy was identified; (2) any reference standard was
      used; (3) sensitivity and specificity were reported or could be (re-)calculated;
      and, (4) the publication was a full report. Two reviewers independently selected
      studies, and assessed methodological quality. Only six studies met the inclusion
      criteria, which evaluated five provocative tests. In general, Spurling's test
      demonstrated low to moderate sensitivity and high specificity, as did
      traction/neck distraction, and Valsalva's maneuver. The upper limb tension test
      (ULTT) demonstrated high sensitivity and low specificity, while the shoulder
      abduction test demonstrated low to moderate sensitivity and moderate to high
      specificity. Common methodological flaws included lack of an optimal reference
      standard, disease progression bias, spectrum bias, and review bias. Limitations
      include few primary studies, substantial heterogeneity, and numerous
      methodological flaws among the studies; therefore, a meta-analysis was not
      conducted. This review suggests that, when consistent with the history and other
      physical findings, a positive Spurling's, traction/neck distraction, and
      Valsalva's might be indicative of a cervical radiculopathy, while a negative ULTT
      might be used to rule it out. However, the lack of evidence precludes any firm
      conclusions regarding their diagnostic value, especially when used in primary
      care. More high quality studies are necessary in order to resolve this issue.

PMID- 17013657
TI  - Technical strategies and anatomic considerations for parapedicular access to
      thoracic and lumbar vertebral bodies.
AB  - OBJECTIVES: To investigate and illustrate a variation on the traditional
      percutaneous access to the vertebral body via a parapedicular approach. DESIGN:
      An effective parapedicular access technique that could safely and reliably guide
      the needle tip into the center of the vertebral body was developed from cadaver
      dissection observations for the purpose of clinical use. PATIENTS: A total of 102
      vertebral compression fractures from T-4 to L-5 were treated via the
      parapedicular access at our institution between July 2005 and March 2006. There
      were 72 patients between the ages of 17 and 96 years (mean age: 68.2 years) who
      underwent treatment. RESULTS: The cadaver dissection revealed a relatively
      avascular and aneural portion of the vertebral body along the superior margin of
      the vertebral body-pedicle junction. A total 102 vertebral fractures were treated
      using the parapedicular access technique without any recognized clinical
      complications from the needle access or the instrumentation. CONCLUSIONS: The
      thoracic and lumbar vertebral bodies may be safely, reliably, and reproducibly
      accessed using a percutaneous parapedicular access technique. The technique
      presented represents a relatively avascular and aneural approach to vertebral
      body.

PMID- 17013658
TI  - The impact of blood rheology on the molecular and cellular events underlying
      arterial thrombosis.
AB  - There is an increasing appreciation of the importance of disturbed blood flow,
      especially turbulent flow, in the pathogenesis of vascular disease. However, the
      precise mechanism(s) by which rheological changes accelerate the atherothrombotic
      process remains incompletely understood. Atherosclerotic lesions typically
      develop in vascular regions exhibiting bifurcated or curved architectures. Such
      regions exhibit complex blood flow profiles with considerable divergence from
      uniform laminar flow. These altered flow behaviours can promote deposition of pro
      atherogenic lipids and proteins to the vessel wall and modulate the adhesive
      function of endothelial, platelets and leukocytes. Once developed,
      atherosclerotic lesions can further exacerbate flow disturbances, establishing a
      potential hazardous cycle of accelerated atherogenesis. At the cellular level,
      alterations in fluid flow can lead to significant changes in signal transduction,
      leading to a variety of functional and morphological changes. In particular,
      disturbed rheology has a significant impact on the adhesion and activation
      mechanisms utilised by platelets and leukocytes with high shear, playing an
      important role in accelerating platelet activation and thrombus growth. This
      review focuses on the impact of blood rheology on the cellular and molecular
      events underlying thrombosis, with particular emphasis on the role of platelets
      in this process.

PMID- 17013659
TI  - Experimental measurement of tibiofemoral contact area in a meniscectomized ovine
      model using a resistive pressure measuring sensor.
AB  - Animal models are necessary for the development and analysis of surgical
      techniques in meniscal surgery because they are the only means of preclinically
      determining the influence of biological factors such as healing processes and
      joint remodeling. Furthermore, little is known about the biomechanical effect of
      meniscectomy in sheep. The aim of the study was thus to investigate the efficacy
      of using a resistive pressure measuring sensor to quantify the effect of chronic
      meniscectomy in an ovine model. Twelve sheep were divided into two groups (n =
      6): a sham operated control group (A), and a medially meniscectomized group (B).
      After six months, lower limb specimens were loaded with a joint-compressive force
      of 500 N during which the pressure measuring sensor was positioned underneath the
      meniscus to determine contact area, mean and peak contact pressure. A significant
      reduction in contact area of about 55% was observed in the meniscectomized knees
      compared to the controls. Peak contact pressure of the meniscectomized knees
      significantly increased an average of 260.4% compared to the control knees. Based
      on the results of this study, we conclude that the resistive pressure measuring
      sensors provide a means to experimentally measure tibiofemoral contact mechanics
      even in this relatively small (compared to human) animal model.

PMID- 17013660
TI  - Two-dimensional dynamic simulation of platelet activation during mechanical heart
      valve closure.
AB  - A major drawback in the operation of mechanical heart valve prostheses is
      thrombus formation in the near valve region. Detailed flow analysis in this
      region during the valve closure phase is of interest in understanding the
      relationship between shear stress and platelet activation. A fixed-grid Cartesian
      mesh flow solver is used to simulate the blood flow through a bi-leaflet
      mechanical valve employing a two-dimensional geometry of the leaflet with a pivot
      point representing the hinge region. A local mesh refinement algorithm allows
      efficient and fast flow computations with mesh adaptation based on the gradients
      of the flow field in the leaflet-housing gap at the instant of valve closure.
      Leaflet motion is calculated dynamically based on the fluid forces acting on it
      employing a fluid-structure interaction algorithm. Platelets are modeled and
      tracked as point particles by a Lagrangian particle tracking method which
      incorporates the hemodynamic forces on the particles. A platelet activation model
      is included to predict regions which are prone to platelet activation. Closure
      time of the leaflet is validated against experimental studies. Results show that
      the orientation of the jet flow through the gap between the housing and the
      leaflet causes the boundary layer from the valve housing to be drawn in by the
      shear layer separating from the leaflet. The interaction between the separating
      shear layers is seen to cause a region of intensely rotating flow with high shear
      stress and high residence time of particles leading to high likelihood of
      platelet activation in that region.

PMID- 17013661
TI  - Individual variation in alkaloid content of poison frogs of Madagascar (Mantella;
      Mantellidae).
AB  - Brightly colored Malagasy poison frogs, Mantella spp., sequester lipophilic,
      basic alkaloids from arthropod prey for their own chemical defense. Consequently,
      microsympatric prey diversity is expected to influence alkaloid diversity
      observed in poison frogs. Twenty-two specimens of three Mantella species from
      four localities in moist forests of southeastern Madagascar were analyzed
      individually via gas chromatography-mass spectrometry, revealing that they
      contain over 80 known alkaloids. Frogs within a locality possessed significantly
      similar alkaloid content and diversity, while frogs from areas that varied in
      disturbance, elevation, and/or species showed greater differences. Based on
      dietary data, the larger frog species Mantella baroni consumed more and larger
      prey, and showed greater diversity in skin alkaloids than significantly smaller
      Mantella bernhardi. Additionally, frogs from the most pristine locality had the
      greatest number of alkaloids, whereas individuals from the most disturbed
      localities had the least. In a comparison of frog alkaloid profiles over a 10- to
      14-yr period, alkaloid turnover, and thus presumably alkaloid-source arthropod
      turnover, was high in a disturbed locality and low in the pristine primary forest
      locality. We demonstrate that the nonlethal transcutaneous amphibian stimulator
      (TAS) is effective for harvesting alkaloids from poison frogs; future studies
      using this device could obtain larger sample sizes without harming local frog
      populations.

PMID- 17013662
TI  - Structure-activity relationships of benzoic acid derivatives as antifeedants for
      the pine weevil, Hylobius abietis.
AB  - Aromatic organic compounds found in the feces of the pine weevil, Hylobius
      abietis (L.) (Coleoptera: Curculionidae), have been shown to deter feeding
      behavior in this species, which is a serious pest of planted conifer seedlings in
      Europe. We evaluated 55 benzoic acid derivatives and a few homologs as
      antifeedants for H. abietis. Structure-activity relationships were identified by
      bioassaying related compounds obtained by rational syntheses of functional group
      analogs and structural isomers. We identified five main criteria of efficiency as
      antifeedants among the benzoic acid derivatives. By predicting optimal structures
      for H. abietis antifeedants, we attempted to find a commercial antifeedant to
      protect conifer seedlings against damage by H. abietis in regenerating forests.
      New, highly effective antifeedants are methyl 2,4-dimethoxybenzoate, isopropyl
      2,4-dimethoxybenzoate, methyl 2-hydroxy-3-methoxybenzoate, methyl (3,5
      dimethoxyphenyl)acetate, and methyl (2,5-dimethoxyphenyl)acetate. Of these,
      methyl 2,4-dimethoxybenzoate and isopropyl 2,4-dimethoxybenzoate have the highest
      antifeedant indices of all substances tested and are the best candidates for
      practical applications in order to protect planted seedlings in the field.

PMID- 17013663
TI  - The evaluation of the oxidant injury as a function of time following brain
      irradiation in a rat model.
AB  - This study presents the evaluation of the oxidant injury as a function of time
      following brain irradiation in a rat model. Thirty-five Wistar rats were divided
      into seven groups. The rats in Group 1 through Group 6 underwent irradiation,
      whereas the rats in Group 7 underwent sham irradiation. The rats in Group 1
      through Group 6 underwent euthanasia at 1 through 48 h following irradiation,
      whereas the rats in Group 7 underwent euthanasia immediately following sham
      irradiation. At the time of euthanasia, the brain tissue was dissected for
      evaluation of the malondialdehyde (MDA) level and the superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GSHPX) activities. The mean MDA levels
      were increased and the mean SOD, CAT and GSHPX activities were decreased at all
      of the time points for evaluation for the rats that underwent irradiation as
      compared to the rats that underwent sham irradiation, substantial for Group 1 and
      gradually leveling out through Group 6. This study confirms that the oxidant
      injury is evaluated at its best through the first several hours following brain
      irradiation.

PMID- 17013665
TI  - Experiencing leisure in later life: a study of retirees and activity in
      Singapore.
AB  - In a society faced with rapid aging and extended life expectancy, older persons
      in Singapore are just beginning to see retirement as a new era in their lives
      that can be quite different from the later life experiences of their own parents.
      Presenting an ethnographic case study of one of the first retiree activity
      centers in Singapore, this article will examine (a) how older persons cope with
      retirement, social, and cultural norms, and (b) the strategies older adults adopt
      in order to stay relevant in a fast-paced society. The ethnographic study shows
      that extrafamilial social support and opportunities for new experiences in
      learning and leisure contribute significantly to positive and active living in
      old age. Although the discussion of aging in Asia usually focuses on the problems
      of health, finances, and caregiving, the present study suggests the need for
      policy makers to pay equal attention to issues such as activity participation in
      old age. Participation in leisure activities may act as a preventive measure to
      delay the onset of aging-related problems, while at the same time enhancing life
      satisfaction among seniors.

PMID- 17013664
TI  - Comparative study of functional limitation and disability in old age: Delhi and
      New York city.
AB  - Cross-national variation in elder health is well established, with older adults
      in developing countries reporting poorer health than elders in developed
      countries. However, cross-national research using performance-based assessment is
      rare. We examined grip strength in American and Indian elders using a common
      methodology and found that older adults in India had significantly poorer
      strength than the US sample even when matched for age, gender, medical
      conditions, and self-rated disability. The difference in performance is likely
      explained by life-long differences in nutrition, occupational demands, and access
      to medical care. These differences in health among people who have survived to
      old age may also explain differences in life expectancy in later life.

PMID- 17013667
TI  - Diversity and structure of intergenerational relationships: elderly parent-adult
      child relations in Korea.
AB  - Korean society has undergone a rapid demographic transition that has challenged
      traditional patterns of family exchanges. The structure and directions of support
      flows have become more complex as multiple generations coexist. This article
      examines the complexity of contemporary Korean intergenerational relationships.
      The study analyzed two different samples to address anticipated differences in
      perceptions of and attitudes toward relationships between adult children and
      elderly parents. The researchers used maximum likelihood latent structure
      analysis to discover the latent patterns of the association among three main
      subdimensions of intergenerational relationships: geographic proximity, exchange
      of support, and cultural norms of family support. Results show that the
      perspectives on intergenerational relationships differ significantly between
      middle-aged children and elderly parents. Intergenerational relationships among
      middle-aged adults comprise five distinct patterns: strong reciprocal, strong
      traditional, intermediate normative, intermediate circumstantial, and weak. The
      interpretation of intergenerational relationships from the elders' perspectives
      is more straightforward, with only three patterns: traditional, reciprocal, and
      weak. Along with significant socioeconomic differences in the prevalent patterns
      of intergenerational relationships, these results emphasize the complex interplay
      of contingency and path dependency in diversifying the value and support
      exchanges of intergenerational relationships.

PMID- 17013668
TI  - Introduction: Aging in Asia--perennial concerns on support and caring for the
      old.
AB  - This introductory article provides background to an understanding of "Aging in
      Asia," focusing on the demographics of population aging in Asia. It discusses the
      differences in the magnitude of the aged population in different parts of Asia
      and highlights the perennial concerns of care and support facing the aged and
      their families as Asian societies grapple with the graying population.
      Globalization is one important factor presenting new challenges as well as
      opportunities to aging Asia. The introduction substantiates the discussions in
      this special issue, which range from an examination of broad issues of support
      for the aged and policy directions in East and Southeast Asia, to specific
      concerns relating to activity and elderly in Singapore, intergenerational
      relationships in Korea, and issues concerning caregiving of the old in Singapore.

PMID- 17013669
TI  - Older Asian Indians resettled in America: narratives about households, culture
      and generation.
AB  - Immigration in late life can be a complex experience. Older adults who have spent
      a considerable part of their life in one cultural milieu face several challenges
      in adapting to a new societal framework. Demographically speaking, the numbers of
      immigrants of Asian Indian origin continue to rise phenomenally in the United
      States. In this project, the experience of Asian Indian elderly immigrants to the
      United States was recorded through home visits and personal interviews. Parents
      of adult immigrants often choose to immigrate late in life primarily for purposes
      of family reunification. Providing assistance with raising grandchildren was also
      an important consideration. This article explores various aspects that surfaced
      from the analysis of interviews; these include personal investment in adult
      children, language/cultural barriers, use of formal services, acculturative
      experience, aging in India, intergenerational relationships, and expectations for
      the future. The findings highlight the need for gerontological research that is
      culturally attuned to the needs of these elders so service delivery may be
      optimally provided.

PMID- 17013670
TI  - Intergenerational communication beliefs across the lifespan: comparative data
      from Ghana and South Africa.
AB  - This paper examines (for the first time) young adult American, Ghanaian, and
      Black South Africans' perceptions of communication and aging. Irrespective of
      cultural background, as age of target increased, so did trait attributions of
      benevolence, norms of politeness and deference, and communicative respect and
      avoidance; however, attributions of personal vitality and communication
      satisfaction decreased linearly. Young adults' reported avoidant communication
      with older people negatively predicted their conversational satisfaction and
      enjoyment of it. In addition, communicative respect was more strongly predictive
      of Africans' satisfaction while certain age stereotypes had contrastive effects
      for the Ghanaian and South Africans' enjoyment of intergenerational
      communication.

PMID- 17013671
TI  - Assessment of quality of outcomes within a local United Way organization:
      implications for sustaining system level change.
AB  - This paper provides a historical case study of efforts to implement and sustain
      "outcomes based funding" in a large United Way system in Central Ohio. The case
      study describes how community practitioners employed specific strategies to
      promote sustainability. The use of these strategies corresponds to several
      techniques suggested in the sustainability literature. This case study is offered
      as a means of considering how practitioners helped sustain the shift to outcomes
      based funding within the United Way system. In addition, this case study
      demonstrates how skills related to implementation and sustainability might be
      transferred to other situations where practitioners are interested in promoting
      change within large organizations and/or communities. The authors suggest that
      skills related to implementation and sustainability are essential to community
      practice.

PMID- 17013672
TI  - Peer standing and substance use in early-adolescent grade-level networks: a short
      term longitudinal study.
AB  - Two competing hypotheses were tested concerning the associations between current
      alcohol and cigarette use and measures of individual, group and network peer
      standing in an ethnically-diverse sample of 156 male and female adolescents
      sampled at two time points in the seventh grade. Findings lent greater support to
      the person hypothesis, with early regular substance users enjoying elevated
      standing amongst their peers and maintaining this standing regardless of their
      maintenance of or desistance from current use later in the school year. In the
      fall semester, users (n=20, 13%) had greater social impact, were described by
      their peers as more popular, and were more central to the peer network than
      abstainers (i.e., those who did not report current use).Conversely, in the spring
      semester, there were no differences between users (n=22, 13%) and abstainers in
      peer ratings of popularity or social impact. Notably, the spring semester users
      group retained fewer than half of the users from the fall semester. Further,
      students who had reported current use in the fall, as a group, retained their
      positions of elevated peer standing in the spring, compared to all other
      students, and continued to be rated by their peers as more popular and as having
      greater social impact. We discuss the findings in terms of the benefit of
      employing simultaneous systemic and individual measures of peer standing or group
      prominence, which in the case of peer-based prevention programs, can help clarify
      the truly influential from the "pretenders" in the case of diffusion of risk
      related behaviors.

PMID- 17013675
TI  - Determination of trace mercury by solid substrate-room temperature phosphorimetry
      quenching method based on catalytic effect of Hg2+ on formation of the ion
      association complex [Sn(XO)6]4+.[(Fin)4].
AB  - A new method for the determination of trace mercury by solid substrate-room
      temperature phosphorimetry (SS-RTP) quenching method has been established. In
      glycine-HCl buffer solution, xylenol orange (XO) can react with Sn4+ to form the
      complex [Sn(XO)6]4+. [Sn(XO)6]4+ can interact with Fin- (fluorescein anion) to
      form the ion associate [Sn(XO)6]4+.[(Fin)4]-, which can emit strong and stable
      room temperature phosphorescence (RTP) on polyamide membrane (PAM). Hg2+ can
      catalyze H2O2 oxidizing the ion association complex [Sn(XO)6]4+.[(Fin)4]-, which
      causes the RTP to quench. The DeltaIp value is directly proportional to the
      concentration of Hg2+ in the range of 0.016-1.6 fg spot(-1) (corresponding
      concentration: 0.040-4.0 pg ml(-1), 0.40 microl spot(-1)), and the regression
      equation of working cure is DeltaIp=10.03+83.15 m Hg2+ (fg spot(-1)), (r=0.9987,
      n=6) and the detection limit (LD) is 3.6 ag spot(-1)(corresponding concentration:
      9.0 x 10(-15) g ml(-1), the sample volume: 0.4 microl). This simple, rapid,
      accurate method is of high selectivity and good repeatability, and it has been
      successfully applied to the determination of trace mercury in real samples. The
      reaction mechanism for catalyzing H2O2 oxidizing the ion association complex
      ([Sn(XO)6]4+.[(Fin)4]-) SS-RTP quenching method to determine trace mercury is
      also discussed.

PMID- 17013673
TI  - Brief report: effect of maternal age on severity of autism.
AB  - The etiology of autism is complex, consisting of unknown genetic and
      environmental factors. Previous studies have revealed that maternal age is
      increased in autism compared to controls, making it a possible risk factor. This
      study examined the effects of maternal age on autism severity using IQ as a
      measure of cognitive severity and selected subtests of the Child Behavior
      Checklist (CBCL) as measures of social severity. A sample of 154 subjects with
      autism spectrum disorders was obtained from the Stanford
      Neuropsychiatry/Pervasive Developmental Disorder (PDD) clinic. Results indicate
      that there is no relationship between IQ or selected CBCL subtests and maternal
      age, suggesting that maternal age does not influence the severity of autism as
      measured by these indicators.

PMID- 17013676
TI  - How phospholipid-cholesterol interactions modulate lipid lateral diffusion, as
      revealed by fluorescence correlation spectroscopy.
AB  - Cholesterol is a key player in regulating physico-chemical properties of cellular
      membranes and, thereby, ensuring cell viability. In particular, lipid-cholesterol
      interactions may provide important information on the spatio-temporal
      organization of membrane components. Here, we apply confocal imaging and
      Fluorescence Correlation Spectroscopy (FCS) to Giant Unilamellar Vesicles (GUVs)
      composed of binary mixtures of lipids and cholesterol. The effect of cholesterol
      on lipid dynamics and molecular packing order of unsaturated, monounsaturated,
      fully saturated (with both low and high phase transition temperatures, Tm)
      glycero-phospholipids and sphingomyelin has been investigated. We show that, for
      unsaturated glycerophospholipids, the decrease of the lipid diffusion coefficient
      as a result of the interaction with cholesterol does not depend on the fatty acid
      chain length. However, the values of the diffusion coefficient change as a
      function of chain length. The monounsaturated phospholipid palmitoyl-oleoyl
      phosphatidylcholine (POPC) exhibits a dynamic behavior very similar to the
      unsaturated dioleoyl-phosphatidylcholine (DOPC). By contrast, for saturated (low
      Tm) glycero-phospholipids, cholesterol causes a decrease of lipid mobility in a
      chain length-dependent manner. FCS can be employed as a valuable tool to study
      lipid-sterol interactions and their effect on lipid dynamics, molecular packing
      and degree of conformational order.

PMID- 17013677
TI  - Fluorescence imaging of heat-stress induced mitochondrial long-term
      depolarization in breast cancer cells.
AB  - Various thermotherapies are based on the induction of lethal heat in target
      tissues. Spatial and temporal instabilities of elevated temperatures induced in
      therapy targets require optimized treatment protocols and reliable temperature
      control methods during thermotherapies. Heat-stress induced effects on
      mitochondrial transmembrane potentials were analyzed in breast cancer cells,
      species MX1, using the potential sensor JC-1 (Molecular Probes, Invitrogen,
      Germany). Potential dependant labeling of heat-stressed cells was imaged and
      evaluated by fluorescence microscopy and compared with control cells. JC-1 stains
      mitochondria in cells with high mitochondrial potentials by forming orange-red
      fluorescent J-aggregates while in cells with depolarized or damaged mitochondria
      the sensor dye exists as green fluorescent monomers. In MX1 cells orange-red and
      green fluorescence intensities were correlated with each other after various heat
      stress treatments and states of mitochondrial membrane potentials were deduced
      from the image data. With increasing stress temperatures the intensity of red
      fluorescent J-aggregates decreased while the green fluorescence intensity of JC-1
      monomers increased. This heat-stress response happened in a nonlinear manner with
      increasing temperatures resulting in a nonlinear increase of red/green
      fluorescence ratios. These data indicated that mitochondria in MX1 cells were
      increasingly depolarized in response to increasing ambient temperatures.

PMID- 17013678
TI  - Presence: the touch of the puppet.
AB  - Using the ideal of the puppet as model and foil, this article looks at ideas
      about presence, play, animation, and belief. Puppetry's role as a vital,
      theatrical form has deep roots in universal, cultural experience, and the notion
      of an inhering spirit that acts for and through image, idol, toy, or fetish is
      perhaps the central thread running through all attempts to represent and simulate
      animate life. Through a discussion of the phenomenology of the puppet--the source
      of its sensory, aesthetic, and metaphysical power--questions are raised about the
      projection of desire and purpose onto other transitional things, real and
      imagined.

PMID- 17013679
TI  - Mercury accumulation in soils and plants in the Almaden mining district, Spain:
      one of the most contaminated sites on Earth.
AB  - Although mercury (Hg) mining in the Almaden district ceased in May 2002, the
      consequences of 2000 years of mining in the district has resulted in the
      dissemination of Hg into the surrounding environment where it poses an evident
      risk to biota and human health. This risk needs to be properly evaluated. The
      uptake of Hg has been found to be plant-specific. To establish the different
      manners in which plants absorb Hg, we carried out a survey of Hg levels in the
      soils and plants in the most representative habitats of this Mediterranean area
      and found that the Hg concentrations varied greatly and were dependent on the
      sample being tested (0.13-2,695 microg g(-1) Hg). For example, the root samples
      had concentrations ranging from 0.06 (Oenanthe crocata, Rumex induratus) to 1095
      (Polypogon monspeliensis) microg g(-1) Hg, while in the leaf samples, the range
      was from 0.16 (Cyperus longus) to 1278 (Polypogon monspeliensis) microg g(-1) Hg.
      There are four well-differentiated patterns of Hg uptake: (1) the rate of uptake
      is constant, independent of Hg concentration in the soil (e.g., Pistacia
      lentiscus, Quercus rotundifolia); (2) after an initial linear relationship
      between uptake and soil concentration, no further increase in Hg(plant) is
      observed (e.g., Asparagus acutifolius, Cistus ladanifer); (3) no increase in
      uptake is recorded until a threshold is surpassed, and thereafter a linear
      relationship between Hg(plant) and Hg(soil) is established (e.g., Rumex
      bucephalophorus, Cistus crispus); (4) there is no relationship between Hg(plant)
      and Hg(soil )(e.g., Oenanthe crocata and Cistus monspeliensis). Overall, the Hg
      concentrations found in plants from the Almaden district clearly reflect the
      importance of contamination processes throughout the study region.

PMID- 17013680
TI  - Quantifying Lipari-Szabo modelfree parameters from 13CO NMR relaxation
      experiments.
AB  - It is proposed to obtain effective Lipari-Szabo order parameters and local
      correlation times for relaxation vectors of protein (13)CO nuclei by carrying out
      a (13)CO-R(1) auto relaxation experiment, a transverse (13)CO CSA/13CO-13Calpha
      CSA/dipolar cross correlation and a transverse (13)CO CSA/(13)CO-(15)N
      CSA/dipolar cross correlation experiment. Given the global rotational correlation
      time from (15)N relaxation experiments, a new program COMFORD (CO-Modelfree
      Fitting Of Relaxation Data) is presented to fit the (13)CO data to an effective
      order parameter S2CO, an effective local correlation time and the orientation of
      the CSA tensor with respect to the molecular frame. It is shown that the
      effective S2CO is least sensitive to rotational fluctuations about an imaginary
      Calpha-Calpha axis and most sensitive to rotational fluctuations about an
      imaginary axis parallel to the NH bond direction. As such, the Calpha-Calpha
      information is fully complementary to the (15)N relaxation order parameter, which
      is least sensitive to fluctuations about the NH axis and most sensitive to
      fluctuations about the Calpha-Calpha axis. The new paradigm is applied on data of
      Ca(2+) saturated Calmodulin, and on available literature data for Ubiquitin. Our
      data indicate that the S2CO order parameters rapport on slower, and sometimes
      different, motions than the (15)N relaxation order parameters. The CO local
      correlation times correlate well with the calmodulin's secondary structure.

PMID- 17013681
TI  - Enhanced signal dispersion in saturation transfer difference experiments by
      conversion to a 1D-STD-homodecoupled spectrum.
AB  - The saturation transfer difference (STD) experiment is a rich source of
      information on topological aspects of ligand binding to a receptor. The epitope
      mapping is based on a magnetization transfer after signal saturation from the
      receptor to the ligand, where interproton distances permit this process. Signal
      overlap in the STD spectrum can cause difficulties to correctly assign and/or
      quantitate the measured enhancements. To address this issue we report here a
      modified version of the routine experiment and a processing scheme that provides
      a 1D-STD homodecoupled spectrum (i.e. an experiment in which all STD signals
      appear as singlets) with line widths similar to those in original STD spectrum.
      These refinements contribute to alleviate problems of signal overlap. The
      experiment is based on 2D-J-resolved spectroscopy, one of the fastest 2D
      experiments under conventional data sampling in the indirect dimension, and
      provides excellent sensitivity, a key factor for the difference experiments.

PMID- 17013682
TI  - Mapping protein-protein interaction by 13C'-detected heteronuclear NMR
      spectroscopy.
AB  - The copper-mediated protein-protein interaction between yeast Atx1 and Ccc2 has
      been examined by protonless heteronuclear NMR and compared with the already
      available (1)H-(15)N HSQC information. The observed chemical shift variations are
      analyzed with respect to the actual solution structure, available through
      intermolecular NOEs. The advantage of using the CON-IPAP spectrum with respect to
      the (1)H-(15)N HSQC resides in the increased number of signals observed,
      including those of prolines. CBCACO-IPAP experiments allow us to focus on the
      interaction region and on side-chain carbonyls, while a newly designed CEN-IPAP
      experiment on side-chains of lysines. An attempt is made to rationalize the
      chemical shift variations on the basis of the structural data involving the
      interface between the proteins and the nearby regions. It is here proposed that
      protonless (13)C direct-detection NMR is a useful complement to (1)H based NMR
      spectroscopy for monitoring protein-protein and protein-ligand interactions.

PMID- 17013684
TI  - Acidosis augments myogenic constriction in rat coronary arteries.
AB  - The myogenic response is a process by which blood vessels autoregulate vascular
      smooth muscle tone in response to changes in transmural pressure. It is
      characterized by vessel contraction or dilation with increased or decreased
      pressure, respectively. We sought to identify whether acidosis impacts the
      myogenic response in rat coronary resistance arteries. Ventricular septal
      arteries were isolated from male Sprague-Dawley rats and mounted on a pressure
      myograph. The myogenic response was assessed by measuring the arterial diameter
      at pressures of 10-120 mm Hg. The fluorescence indicators 2',7'-bis
      (carboxyethyl)-5(and-6)-carboxyfluorescein and Fura-2 were utilized to measure
      intracellular pH (pH(i)) and intracellular free calcium concentration
      ([Ca(2+)](i)), respectively. A decrease in the extracellular pH (pH(o)) from 7.4
      to 6.9 produced a fall in pH(i) and an increase in the myogenic response. Under
      nominally HCO (3) (-) /CO(2)-free conditions at a constant pH(o), blockade of the
      sodium-hydrogen exchanger with HOE694 also resulted in a fall in pH(i) and a
      similar enhancement of myogenic activity. Concentration response curves were
      constructed to measure the potencies of the HOE694 effects: the EC(50) was 34
      microM for the pH(i) change and 19 microM for vessel constriction. Apparent
      [Ca(2+)](i) remained unchanged during HOE694-induced intracellular acidification.
      Furthermore, in the presence of HCO (3) (-) , HOE694 did not markedly affect
      pH(i) and vascular tone remained unaltered. Our data demonstrate that acidosis
      augments myogenic constriction of rat coronary arteries. These effects are due to
      a fall in pH(i) consequent upon the reduction in pH(o) and may reflect an
      increased myofilament [Ca(2+)](i) sensitivity within vascular smooth muscle
      cells.

PMID- 17013683
TI  - Measurement of 15N relaxation in the detergent-solubilized tetrameric KcsA
      potassium channel.
AB  - A set of TROSY-HNCO (tHNCO)-based 3D experiments is presented for measuring (15)N
      relaxation parameters in large, membrane-associated proteins, characterized by
      slow tumbling times and significant spectral overlap. Measurement of backbone
      (15)N R (1), R (1rho), (15)N-{(1)H} NOE, and (15)N CSA/dipolar cross correlation
      is demonstrated and applied to study the dynamic behavior of the homotetrameric
      KcsA potassium channel in SDS micelles under conditions where this channel is in
      the closed state. The micelle-encapsulated transmembrane domain, KcsA(TM),
      exhibits a high degree of order, tumbling as an oblate ellipsoid with a global
      rotational correlation time, tau(c) = 38 +/- 2.5 ns, at 50 degrees C and a
      diffusion anisotropy, Dparallel/Dperpendicular = 0.79+/-0.05, corresponding to an
      aspect ratio a/b >/= 1.4. The N- and C-terminal intracellular segments of KcsA
      exhibit considerable internal dynamics (S (2) values in the 0.2-0.45 range), but
      are distinctly more ordered than what has been observed for unstructured random
      coils. Relaxation behavior in these domains confirms the position of the C
      terminal helix, and indicates that in SDS micelles, this amphiphilic helix does
      not associate into a stable homotetrameric helical bundle. The relaxation data
      indicate the absence of elevated backbone dynamics on the ps-ns time scale for
      the 5-residue selectivity filter, which selects K(+) ions to enter the channel.

PMID- 17013685
TI  - Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in
      gastrointestinal stromal tumors: prognostic implications and correlations with
      risk stratification of NIH consensus criteria.
AB  - BACKGROUND: Inactivation of p16(INK4A) promotes G1/S progression of cell cycle.
      Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker,
      is known to better correlate with clinical outcomes than Ki-67 in many
      carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains
      challenging in prognostication, we analyzed the utility of these three markers in
      GISTs. METHODS: Immunohistochemistry was performed in tissue microarrays of 277
      primary GISTs and correlated with NIH consensus criteria and clinical outcomes.
      RESULTS: The increment of NIH risk levels significantly correlated with
      increasing labeling indices (LI) of both Ki-67 (P <.001) and Mcm2 (P <.001) and
      loss of p16(INK4A) expression (P <.035). However, the latter aberration did occur
      in 23% of very low/low-risk GISTs. The relationship between Mcm2 and Ki-67 LIs
      could be modeled as linear (P <.001, r = 0.697), while Mcm2 LI was considerably
      higher (P <.001) with a stepwise escalation related to risk levels. Ki-67 LI >5%
      (P <.0001) and Mcm2 LI >10% (P <.0001) were strongly predictive of inferior
      disease-specific survival (DSS), while aberrant loss of p16(INK4A) only reached a
      trend (P = .0954). In multivariate analyses, independent adverse factors of DSS
      were high-risk category (RR = 16.93, P <.0001), metastatic disease (RR = 4.12, P
      = .0015), Ki-67 LI >5% (RR = 3.55, P = .001), and presence of epithelioid
      histology (RR = 2.17, P = .0308). CONCLUSIONS: Prognostic efficacy of NIH
      consensus criteria is substantiated. P16(INK4A) deregulation can occur early in
      GIST tumorigenesis and marginally correlates with patient survival. Despite Ki-67
      LI being an independent prognosticator, simultaneous detection of Mcm2 is
      recommended as a prognostic adjunct of GISTs, given its better sensitivity and
      stepwise escalation with increasing risk levels.

PMID- 17013686
TI  - Toxicity and quality of life after cytoreductive surgery plus hyperthermic
      intraperitoneal chemotherapy.
AB  - BACKGROUND: The purpose of our study was to determine the toxicity and quality of
      life for patients with peritoneal metastases after cytoreductive surgery (CS)
      plus hyperthermic intraperitoneal chemotherapy (HIPC). METHODS: From 2001 to
      2005, 35 consecutive patients with peritoneal metastases enrolled in a
      prospective trial approved by the University of Minnesota Institutional Review
      Board. Their primary cancer sites included the appendix (19 patients), colon (7),
      mesothelioma (3), stomach (2), small bowel (2), gallbladder (1), and unknown (1).
      We performed CS in an effort to remove all or nearly all peritoneal tumor
      nodules. Using a closed technique, we administered hyperthermic mitomycin C into
      the peritoneal cavity for 90 min. Before treatment and then at 4-month
      postoperative intervals, we used the functional assessment of cancer therapy
      colon subscale (FACT-C) instrument to assess the patients' quality of life.
      RESULTS: The median hospital stay was 9 days; 12 patients were hospitalized at
      least 30 days or required readmission within 30 days after treatment. The
      postoperative mortality rate was 0%; adverse events occurred in 18 (51%)
      patients. As of December 2005, 20 patients were alive; 14 had died of progressive
      disease and 1 of an unrelated cause. The median survival time was 21.4 months.
      Quality of life measurements, including trial outcome index (TOI), FACT-colon,
      and FACT-general, returned to baseline 4 months after treatment and were
      significantly improved at 8 and 12 months. CONCLUSIONS: Despite early toxicity,
      CS plus HIPC may prolong the overall survival rate of patients with peritoneal
      metastases and improve quality of life measurements.

PMID- 17013687
TI  - Neoplastic mesorectal microfoci (MMF) following neoadjuvant chemoradiotherapy:
      clinical and prognostic implications.
AB  - BACKGROUND: Neoplastic microfoci have frequently been found in the mesorectum,
      with poor outcome. In this study, incidence and clinical significance of
      mesorectal microfoci (MMF) were analyzed in patients operated upon for rectal
      cancer following neoadjuvant chemoradiation. METHODS: A case series of 68
      patients with extraperitoneal rectal cancer, treated with neoadjuvant
      chemoradiation and surgery (including total mesorectal excision), was
      investigated for the presence of neoplastic MMF. RESULTS: Mesorectal microfoci
      were found in 26 cases (38.2%). Increasing incidence of microfoci was
      statistically related to pathologic involvement of bowel wall (P = 0.0006),
      Mandard's tumor regression grading (P = 0.0006) and pathologic neoplastic
      mesorectal involvement (P < 0.00001). None of the nine patients with complete
      tumor disappearance displayed both microfoci and lymph node metastasis. Only one
      local recurrence developed in a patient with multiple MMF. Out of 9 pT0 or TRG1
      patients, 1 (11.1%) had distant metastases, compared to 15 out of 59 pT1-4 or
      TRG2-5 (25.4%, P = 0.70). CONCLUSIONS: A remarkable incidence of MMF was found
      following chemoradiation. However, when this therapy induces complete regression
      of primary tumor (pT0-TRG1), node metastases and neoplastic MMF could also
      disappear, as shown in our cases. These features should be confirmed because they
      could significantly impact the treatment decision-making of rectal cancers.

PMID- 17013688
TI  - Evaluation of preoperative therapy for pancreatic cancer using a prognostic
      nomogram.
AB  - BACKGROUND: Theoretical benefits of preoperative chemoradiation therapy (preop
      CRT) for pancreatic cancer include improved efficacy, resectability, and patient
      selection. The goal of this study was to evaluate the applicability of a
      nomogram, which was developed for patients undergoing resection without preop CRT
      and which incorporates several post-resection pathological factors, to a
      population of patients who received preop CRT prior to resection. METHODS: From
      1994 to 2004, 82 patients with biopsy-proven, radiographically localized
      adenocarcinoma of the pancreatic head underwent preop CRT followed by
      pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop
      CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared
      with observed DSS rates from the time of resection. RESULTS: Despite having more
      locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who
      received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01),
      were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to
      have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph
      nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and
      favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted
      DSS in both groups. CONCLUSIONS: The similarity in observed and predicted DSS
      following resection in patients who received preop CRT suggests that the effects
      of preop CRT-whether treatment, selection, or no effect-are reflected by the
      nomogram. The ability of the nomogram to evaluate the effects of preop CRT on
      survival is limited by the potential effects of preop CRT on factors within the
      nomogram.

PMID- 17013689
TI  - Assessing the state of surgical oncology: the future is now.
AB  - In assessing the state of surgical oncology, we will need to institute some
      significant and timely changes in order to move our field forward. A number are
      discussed which will have a profound impact on our society and our profession.
      Stimulating the membership to think and to act will result in advancing the field
      and improving patient care.

PMID- 17013690
TI  - Multidetector row CT of various hepatic artery complications after living donor
      liver transplantation.
AB  - Although it is uncommon, hepatic artery (HA) complications including
      pseudoaneurysm, dissection, and flow steal phenomenon as well as stenosis and
      thrombosis may occur after living donor liver transplantation (LDLT). A timely
      diagnosis is of utmost importance for graft and patient survival, because it may
      result in serious complications, such as life-threatening hemorrhage, severe
      graft dysfunction or even failure, bile duct necrosis or stricture. Multidetector
      row CT (MDCT), with superb spatial- and time-resolution, may facilitate the
      diagnosis of HA complications in LDLT recipients. However, little attention has
      been paid to MDCT findings of various HA complications following LDLT. For an
      early recognition and accurate diagnosis of HA complications, radiologists should
      be familiar with their MDCT findings. In this essay, we present a comprehensive
      review of various HA complications after LDLT and illustrate their MDCT findings.

PMID- 17013691
TI  - A novel H572R mutation in the transforming growth factor-beta-induced gene in a
      Thai family with lattice corneal dystrophy type I.
AB  - PURPOSE: To describe a large Thai family with lattice corneal dystrophy (LCD)
      type I and to determine whether this LCD is associated with mutations within the
      transforming growth factor-beta-induced (TGFBI) gene. METHODS: A six-generation
      family with LCD type I was identified and diagnosed on the basis of clinical
      and/or histopathologic evaluation. Visual acuity testing and slit-lamp
      biomicroscopic evaluation were carried out and corneal photography was
      documented. All 17 exons and flanking intron sequences of the TGFBI gene were
      sequenced. RESULTS: Thirty-three participants demonstrated LCD in both eyes, most
      of which was symmetrical. Age at onset of decreased vision was the mid- to late
      twenties. Visual acuity varied from 6/6 to no light perception. Two patients, 74
      and 42 years of age, demonstrated a thick yellowish plaque covering the corneal
      surfaces. DNA sequencing revealed a heterozygous mutation in exon 13 (A1762G),
      changing histidine to arginine at codon 572 (H572R). Ten of 42 clinically
      unaffected family members, all under 25 years of age, exhibited the same
      mutation. CONCLUSIONS: This is the first report of a molecular analysis of LCD
      type I in Thai patients. The novel mutation identified is associated with
      distinct phenotypes and later onset of the disease compared with the more common
      R124C mutation.

PMID- 17013692
TI  - Automated keratoconus detection using height data of anterior and posterior
      corneal surfaces.
AB  - PURPOSE: To develop a keratoconus detection algorithm using the corneal
      topographic data of the anterior and posterior corneal surfaces. METHODS:
      Topographic measurements of the cornea were made with a slit-scanning corneal
      topographer. We examined 120 subjects (165 eyes); keratoconus patients and
      keratoconus suspect patients comprised the keratoconus group, and post
      photorefractive keratectomy patients, with-the-rule astigmatism patients, and
      controls without disease comprised the nonkeratoconus group. Two variables of the
      anterior corneal surface, two variables of the posterior corneal surface, and one
      corneal thickness variable were obtained by applying the Fourier harmonic
      decomposition formula. By performing a logistic regression analysis with a
      training set to differentiate the keratoconus group from the nonkeratoconus
      group, the Fourier-incorporated keratoconus detection Index (FKI) was created.
      The validity of the FKI was determined by using independent validation sets.
      RESULTS: The FKI distinguished the keratoconus group from the nonkeratoconus
      group with 96.9% sensitivity and 95.4% specificity in the validation set.
      CONCLUSIONS: A newly developed automated keratoconus classifier can be used to
      screen keratoconic patients. The index is based on information obtained by
      Fourier analysis from not only the anterior corneal surface but also from the
      posterior corneal surface and corneal thickness.

PMID- 17013694
TI  - Clinical and molecular findings in three Japanese patients with crystalline
      retinopathy.
AB  - PURPOSE: To identify CYP4V2 mutations in three unrelated Japanese patients with
      Bietti crystalline corneoretinal dystrophy (BCD). METHODS: The three cases were
      diagnosed by ophthalmological examinations. All exons and flanking introns were
      amplified by polymerase chain reaction (PCR). PCR products were analyzed by
      direct sequencing. RNA was extracted from blood samples and analyzed by reverse
      transcriptase (RT)-PCR sequencing. RESULTS: Direct PCR sequencing demonstrated a
      homozygous mutation involving a 17-bp deletion together with a 2-bp insertion
      (c.802-8del17bp/insGC) in case 1 and case 3, and RT-PCR demonstrated that the
      complete length of exon 7 was missing; case 2 showed only a heterozygous change
      in exon 11 with no second mutation. CONCLUSION: A homozygous mutation was
      identified in two of the unrelated patients, and only a heterozygous change was
      detected in the third. These data indicate that c.802-8del17bp/insGC may be a
      frequent mutation in this gene.

PMID- 17013693
TI  - Decreased retinal neuronal cell death in caspase-1 knockout mice.
AB  - PURPOSE: To determine whether apoptosis of retinal neurons induced by excessive
      light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout
      mice. METHODS: Eight- to 10-week-old caspase-1 knockout mice (Casp1-/-) and wild
      type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light
      of 25,000 lux for 2 h. Other mice were subjected to retinal ischemia by
      increasing the intraocular pressure to 110 mmHg for 45 min. Electroretinograms
      (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick
      end labeling (TUNEL) was performed to identify the apoptotic cells after the
      insults. The inner retinal thickness was measured to evaluate the retinal injury
      after the ischemia-reperfusion. Expression of caspase-1 protein was studied by
      immunohistochemical analysis and Western blotting. Caspase-1-like protease
      activity was determined by a colorimetric tetrapeptide substrate. RESULTS: The
      morphology of the retina and the amplitudes of the a and b waves of the ERGs of
      Casp1-/- mice did not differ from those of WT mice. After the light exposure,
      TUNEL-positive cells were observed in the outer nuclear layer of the WT mice
      retina. The number of TUNEL-positive photoreceptor nuclei after the light
      exposure, and the number of nuclei in the inner nuclear layer after the ischemia
      reperfusion injury, were significantly less in Casp1-/- mice than in WT mice.
      There were more caspase-1-positive photoreceptor cells in WT mice after the light
      injury. The inner retinal layer of Casp1-/- mice was significantly thicker in
      Casp1-/- mice than in WT mice 2 weeks after the ischemic insult. CONCLUSIONS:
      Retinal neuronal apoptosis was less prominent in Casp1-/- mice after excessive
      light exposure and ischemia-reperfusion injury. These data indicate that caspase
      1 plays a role in retinal neuronal apoptosis.

PMID- 17013695
TI  - The s-wave of the multifocal electroretinogram in cats.
AB  - PURPOSE: To characterize the s-wave of the multifocal electroretinogram (mfERG)
      in cats, and to determine the contribution of the inner retina to the s-wave by
      examining the effects of tetrodotoxin (TTX) and N-methyl D: -aspartate (NMDA)
      injected into the vitreous cavity. METHODS: mfERGs were recorded from 15 eyes of
      15 male cats under general anesthesia. The stimulus consisted of 37 elements, and
      the luminance of the bright and the black elements were 200 and 4 cd/m2,
      respectively. The stimuli were presented in a pseudorandom binary m-sequence at
      six different base periods (bpds) from 13.3 to 426.7 ms. Fifty microliters of 7.0
      microM TTX followed by 50 microl of 4.0 mM NMDA were injected into the vitreous
      cavity. RESULTS: The shape of the mfERGs in the cats resembled that in humans.
      The s-wave appeared on the descending limb of P1, as seen in human mfERGs, in 11
      eyes, and the s-wave amplitude increased significantly as the bpd was increased.
      TTX and NMDA resulted in the disappearance of the s-wave at all bpds, while the
      amplitude of P1 remained unchanged. CONCLUSIONS: The s-wave is present in the
      mfERG in the cat, and its loss following injections of TTX and NMDA supports the
      view that the s-wave reflects the function of the ganglion cells and their axons.

PMID- 17013696
TI  - Influence of accommodative lag upon the far-gradient measurement of accommodative
      convergence to accommodation ratio in strabismic patients.
AB  - PURPOSE: To determine the influence of the lag of accommodation (LOA) on the
      accommodative convergence to accommodation (AC/A) ratio measured by the far
      gradient method in strabismic patients. METHODS: The AC/A ratio was measured with
      a distance target viewed with and without -3.00 diopter (D) addition lenses in 63
      patients with different types of strabismus (age range, 7-34 years; range of
      strabismic angle, -60 to +40 prism diopters; refractive error range, -7.33 to
      +6.63 D). The LOA for the same lens was measured with an open-view-type
      autorefractometer. The stimulus AC/A ratio and the AC/A ratio adjusted by the
      individually measured LOA (adjusted AC/A ratio) were compared. RESULTS: The mean
      +/- SD of the LOA to the -3.00 D lenses was 1.06 +/- 0.43 D. The mean adjusted
      AC/A ratio was 41% greater than the stimulus AC/A ratio. The LOA differed widely
      among patients (0.13 to 2.14 D), and a large LOA tended to appear in myopic or
      young patients. CONCLUSIONS: The AC/A ratio obtained using the conventional far
      gradient method is significantly biased by the LOA, and thus does not always
      represent the actual relationship between accommodation and vergence control
      systems.

PMID- 17013697
TI  - Addition of or switch to topical bunazosin hydrochloride in elderly patients with
      normal-tension glaucoma: A one-year follow-up study.
AB  - PURPOSE: To evaluate the efficacy and safety of 0.01% bunazosin hydrochloride
      ophthalmic solution (bunazosin) for elderly patients with normal-tension glaucoma
      (NTG) as an addition to or instead of their previous therapy. METHODS: Bunazosin
      was administered to NTG patients aged 65 years or over who had been undergoing
      topical glaucoma therapy. In accordance with the study protocol, intraocular
      pressure (IOP) and visual field measurement were performed and the safety of the
      treatment was evaluated periodically between week 0 and week 52 at the five
      facilities where the study was carried out. RESULTS: Of the 98 enrolled patients,
      84 (85.7%) were followed up for 52 weeks. During the follow-up period, IOP
      significantly and persistently decreased (week 0, 15.0 +/- 2.5 mmHg; week 52,
      13.4 +/- 2.4 mmHg, P < 0.0001), but the decrease in mean deviation (MD) was not
      significant. Although no systemic adverse reactions were observed, local adverse
      events were noted in 7 of the 98 patients. CONCLUSIONS: The addition of or the
      switch to bunazosin in elderly NTG patients resulted in a significant reduction
      of IOP without apparent exacerbation of visual field defects or systemic or local
      adverse reactions other than conjunctival hyperemia.

PMID- 17013698
TI  - Diurnal variation of intraocular pressure in suspected normal-tension glaucoma.
AB  - PURPOSE: To assess diurnal variations of intraocular pressure (IOP) in suspected
      normal-tension glaucoma (NTG) patients with subsequent long-term observation to
      detect changes that may lead to a new diagnosis. METHODS: Diurnal variation of
      IOP was measured in a sitting position at 2-h intervals for 24 h in a total of
      569 subjects with suspected NTG. RESULTS: Thirty of the 569 subjects (5.3%)
      showed IOP values exceeding 20 mmHg during the 24-h monitoring and were diagnosed
      as having primary open-angle glaucoma (POAG). In subjects in whom NTG was
      definitely diagnosed based on the results of the 24-h monitoring, the average
      maximum, minimum, and mean IOP was 16.1, 11.7, and 13.9 mmHg, respectively, and
      the mean diurnal variation in IOP was 4.4 mmHg. The peak time was observed
      outside clinic hours (1800-0800) in 41.4% of patients, and the trough time was
      observed during clinic hours (1000-1600) in 15.9%. In 2.9% of NTG subjects, the
      diagnosis was eventually changed to POAG during follow-up. CONCLUSION: Assessment
      of diurnal variations of IOP in suspected NTG patients is useful for the
      differential diagnosis of POAG from NTG and for establishment of a baseline,
      which may affect the management plan.

PMID- 17013699
TI  - The outcome of mitomycin C trabeculectomy and laser suture lysis depends on
      postoperative management.
AB  - PURPOSE: To verify that postoperative management affects the outcome of mitomycin
      C (MMC) trabeculectomy and suture lysis. METHODS: A total of 108 eyes in 108
      Japanese patients were treated with MMC trabeculectomy. They were divided into
      two groups based on when the operation was performed: group A, 57 eyes in 1998,
      and group B, 51 eyes in 2001. The results, including postoperative intraocular
      pressure (IOP), complications, and postoperative management, were compared
      between groups. In addition, they were evaluated by a Kaplan-Meier life-table
      analysis. RESULTS: Postoperative IOP was lower and the probability of success by
      life-table analysis was higher in group B than in group A. Postoperative
      management, including laser suture lysis and subconjunctival injection of 5
      fluorouracil, was started significantly earlier in group B than in group A
      patients. Although more postoperative complications occurred in group B, none
      were severe and all were adequately managed. CONCLUSIONS: Starting postoperative
      management earlier, particularly laser suture lysis, may be necessary to achieve
      lower and longer IOP control in MMC trabeculectomy.

PMID- 17013700
TI  - Serous macular detachment associated with retinal arterial macroaneurysm.
AB  - PURPOSE: To report optical coherence tomography (OCT) findings of macular edema
      secondary to retinal arterial macroaneurysms. METHODS: Six eyes with retinal
      arterial macroaneurysms were retrospectively examined by OCT. All eyes had
      macular edema without massive macular hemorrhage. Fluorescein angiography was
      performed in six eyes, and indocyanine green angiography was done in four eyes.
      Five eyes underwent direct laser photocoagulation to the retinal arterial
      macroaneurysms. The foveal thickness, height of the serous macular detachment,
      and visual acuity (VA) were evaluated from the initial examination until the
      macular edema resolved. RESULTS: In all six eyes, the macular edema secondary to
      retinal arterial macroaneurysms comprised a serous macular detachment with
      retinal swelling. No cystoid macular edema was observed in any eyes. Dye leakage
      occurred only from the macroaneurysms in all eyes. OCT showed complete resolution
      of the serous macular detachment and retinal swelling 1 to 4 months after the
      initial examination. Macular hard exudates developed during absorption of the
      serous macular detachment in all eyes. VA improved more than two lines in all
      eyes after the macular edema resolved. CONCLUSION: Retinal arterial
      macroaneurysms may leak extravasated fluid into the subretinal space, which may
      result in a serous macular detachment.

PMID- 17013701
TI  - Relation between plasma nitric oxide levels and diabetic retinopathy.
AB  - PURPOSE: Nitric oxide (NO) plays an important role in homeostatic vasodilation
      and the regulation of blood flow. On the other hand, excess release of NO causes
      various vascular complications. There are only a few reports on the relationship
      between plasma NO levels and microvascular complications, especially diabetic
      retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was
      to determine the relationship between plasma NO levels and DR. METHODS: In a
      prospective study, blood samples were obtained from 36 patients with diabetes and
      no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic
      retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR),
      and 40 subjects without diabetes mellitus, who served as controls. The levels of
      plasma NOx (nitrite and nitrate), the stable metabolites of NO, were measured by
      high-performance liquid chromatography with the Griess method. RESULTS: The
      plasma NOx levels were 92.8 +/- 16.0, 70.2 +/- 6.8, 90.3 +/- 9.1, and 53.8 +/-
      6.1 micromol/l in patients with NDR, NPDR, or PDR, and in the controls,
      respectively. The plasma NOx levels in the three diabetic groups were
      significantly higher than those in the control group (P < 0.05 in each case).
      CONCLUSION: The increased plasma NO levels in patients with type 2 diabetes
      indicate that NO may be associated with the pathogenesis of DR.

PMID- 17013702
TI  - Metastasis to the orbit from transitional cell carcinoma of the bladder.
AB  - PURPOSE: To demonstrate the pathological features of the extremely rare
      metastatic transitional cell carcinoma (TCC) from the bladder to the orbit, and
      to review the literature on metastatic TCC to the orbit. METHODS: A 74-year-old
      man experienced 2 weeks of red eye, proptosis, diplopia, pain, and visual loss in
      the right eye. Three years previous to the current presentation, the patient had
      undergone a transurethral resection for superficial and moderately differentiated
      TCC of the bladder. A transseptal anterior orbitotomy was performed. RESULTS:
      Histopathological examination of the orbital lesion revealed nests of
      carcinomatous cells. Atypical pleomorphic cells with vacuolated cytoplasm were
      evident. The cellular morphology of the orbital lesion was identical to that of
      the primary TCC. There have been 12 previously reported cases of metastases to
      the orbit from TCC of the bladder, with the time from onset of primary TCC to
      observation of ocular symptoms ranging from 3 weeks to 11 years. Mean survival
      after orbital metastasis developed from TCC was 3.0 months. CONCLUSION: This
      study presents a detailed description of the pathological features of metastatic
      TCC in the orbit. In cases of orbital metastasis from TCC, patient prognosis is
      very poor.

PMID- 17013703
TI  - An Asian patient with intraocular lymphoma treated by intravitreal methotrexate.
AB  - BACKGROUND: To demonstrate the efficacy of intravitreal methotrexate for treating
      intraocular lymphoma. CASE: A 55-year-old immunocompetent Asian man was diagnosed
      with intraocular lymphoma. OBSERVATIONS: The patient was initially managed by
      intravenous administration of high-dose methotrexate. Because vitreous cells
      persisted after systemic chemotherapy, methotrexate was given intravitreally
      thereafter. There was only self-limited corneal epitheliopathy without major
      complications following intraocular injections. Ocular remission was sustained
      during a 21-month follow-up. CONCLUSION: Intravitreal methotrexate is an
      effective, repeatable, and safe treatment for intraocular lymphoma.

PMID- 17013704
TI  - Postoperative assessment of retinal function using a multifocal electroretinogram
      after the removal of subfoveal choroidal neovascularization secondary to age
      related macular degeneration.
AB  - PURPOSE: To assess retinal function in a macular lesion with multifocal
      electroretinography (mfERG) after successful surgical removal of choroidal
      neovascularization (CNV). METHODS: We prospectively studied 15 patients (15 eyes)
      who underwent surgical removal of subfoveal CNV secondary to age-related macular
      degeneration. Three and 6 months after surgery, retinal thickness in the
      parafoveal lesion and the size of the serous retinal detachment (SRD) were
      measured. The mfERG was also recorded, and the data from each of six concentric
      ring annuli were averaged. RESULTS: After surgery, the parafoveal retinal
      thickness significantly decreased compared with the preoperative value, and SRD
      was not recognized in any patient. The change in the amplitude of the P1-wave
      within 2 degrees to 15 degrees in diameter positively correlated with the
      decrease in the parafoveal retinal thickness. Additionally, amplitude within 8
      degrees to 24 degrees in diameter positively correlated with the size of the
      preoperative SRD. CONCLUSION: mfERG is helpful to quantitatively and objectively
      assess the effect of the surgical removal of CNV on retinal function, not only in
      the fovea but also in the entire macular area.

PMID- 17013705
TI  - Prevalence of refractive errors in school-age children in Burkina Faso.

PMID- 17013706
TI  - Relapsing uveitis in association with presumed sinus histiocytosis.

PMID- 17013707
TI  - An unusual cause of persistent bilateral swollen optic discs.

PMID- 17013708
TI  - The impact of 3-D virtual hepatectomy simulation in living-donor liver
      transplantation.
AB  - BACKGROUND/PURPOSE: In living-donor liver transplantation, accurate assessments
      of liver graft volume and anatomical variation are mandatory for the preoperative
      planning of safe donor hepatectomy and successful recipient implantation. The aim
      of this study was to assess the feasibility and accuracy of novel three
      dimensional (3-D) virtual hepatectomy simulation software in living-donor liver
      transplantation. METHODS: We developed the hepatectomy simulation software, which
      was programmed to analyze detailed 3-D vascular structure and to predict liver
      graft volume, based on hepatic circulation. RESULTS: In 101 individuals,
      including 4 living donors, the predicted liver resection volumes revealed a
      significant correlation with the actual value (P < 0.0001), with a mean
      difference of 7.9 ml. The drainage area by the individual hepatic vein branch was
      quantified to achieve reconstruction of the corresponding venous branch. The
      application of multidetector computed technology scanning and virtual
      cholangioscopy facilitated more detailed visualization of the 3-D hilar anatomy
      in a left trisectoral graft transplantation. CONCLUSIONS: This hepatectomy
      simulation software reliably predicted accurate liver graft volume and the
      drainage volume of hepatic vein branches. This software may contribute to the
      preoperative planning of safe donor hepatectomy and implantation with
      satisfactory graft viability.

PMID- 17013709
TI  - Living-donor liver transplantation: an overview.
AB  - It has been 16 years since the first successful living-donor liver transplant was
      performed from a parent to a child. The overall recipient and graft survival,
      together with a low morbidity and mortality in donors, have resulted in the
      widespread acceptance of the procedure by both the transplant community and the
      public at large. Adult-to-adult living-donor liver transplantation has been
      evolving over the past decade. Despite living-donor transplant patients being
      better-risk candidates than those who receive a graft from a deceased donor, and
      well-established and experienced units achieving satisfactory results, overall
      recipient and graft survival recorder by registries can only be described as
      suboptimal. This, combined with the high morbidity and not-insignificant
      mortality amongst donors makes expansion of adult-to-adult liver transplantation
      hard to justify on a risk-benefit analysis.

PMID- 17013710
TI  - Liver transplantation for hepatitis B-related cirrhosis: recent advances.
AB  - In the absence of preventative therapy, deceased-donor liver transplantation
      indicated for hepatitis B virus (HBV) cirrhosis results in dismal graft and
      patient survival due to HBV infection of the liver graft. Major advances in the
      management of HBV-infected recipients during the past 15 years have reduced the
      rate of graft infection, resulting in improved outcomes, comparable to those for
      patients transplanted for non-HBV indications. Long-term use of hepatitis B
      immunoglobulin for passive immunotherapy is effective in preventing re-infection.
      Combination therapy with hepatitis B immunoglobulin and lamivudine after liver
      transplantation reduces HBV recurrence. Adefovir dipoxil is a safe and effective
      alternative oral antiviral treatment for lamivudine-resistant mutant HBV. The
      high cost of hepatitis B immunoglobulin remains a problem that must be overcome
      by the development of HBV vaccines and potent adjuvants.

PMID- 17013711
TI  - Liver transplantation for hepatitis C.
AB  - Hepatitis C virus (HCV) infection is the leading cause of endstage liver disease
      in Western and Asian countries. However, after liver transplantation, HCV recurs
      in virtually all patients, and estimated HCV-related graft cirrhosis at 5-year
      follow-up is 30%. Although immunosuppression accounts for a major part of the
      accelerated progression of HCV in the transplant population, the best
      immunosuppression for recipients with HCV that could avoid such complication
      remains unknown at present. Combination therapy of interferon and ribavirin is
      thought to be the most effective for the treatment or prophylaxis of HCV
      infection. However, who should be treated, when treatment should be initiated,
      and with what agent should patients with HCV infection be treated are still
      unknown. The current data on HCV recurrence in patients who have received either
      living- or deceased-donor liver transplantation are controversial, but they are,
      presumably, similar. Thus, to avoid HCV recurrence in living-donor liver
      transplantation, we have to take approaches similar to those used for patients
      receiving deceased-donor liver transplantation. Based on reports from major
      transplant centers around the world, we consider the best strategy for liver
      transplantation-related HCV infection is steroid-free immunosuppression and
      preemptive low-dose interferon and ribavirin combination therapy. Here we
      describe our experience with living-donor liver transplantion for patients with
      hepatitis C at Osaka University. There is a need for standardizing the treatment
      for HCV infection. This can only be achieved through collaborative work between
      various liver transplant centers worldwide.

PMID- 17013712
TI  - Living-donor liver transplantation for hepatocellular carcinoma.
AB  - Transplant surgeons have long dreamed of achieving a complete cure for
      hepatocellular carcinoma (HCC) by replacing the liver with a new graft. Although
      the early results of liver transplantation for HCC were disappointing, with 5
      year survival less than 40%, improved results in patients who met the so-called
      Milan criteria rekindled the enthusiasm for the treatment of HCC with liver
      transplantation. Furthermore, the recent development of living-donor liver
      transplantation in adults has allowed timely grafting for HCC patients and
      tentative expansion of the criteria for transplant candidacy in patients with HCC
      - although such expansion is fraught with controversy. Identification of a
      noninvasive marker that could predict the biological behavior as well as the
      prognosis of HCC would indeed be a major breakthrough.

PMID- 17013713
TI  - Primary closure of the common bile duct in open laparotomy for common bile duct
      stones.
AB  - It is common these days to treat common bile duct (CBD) stones using endoscopic
      techniques. However, severe complications sometimes lead to death despite the
      great benefit of these techniques. If the patient has many and/or large stones,
      it can take considerable time for duct clearance, and this is associated with
      high costs. Therefore, we do not hesitate to choose surgical procedures when
      necessary. In this study, our aim was to evaluate the usefulness of primary
      closure of the CBD in open laparotomy for CBD stones. Thirty-four patients with
      CBD stones were operated on by open laparotomy; primary closure was done in 17
      patients (group PC), and T-tube insertion was done in 17 (group TT). We compared
      the patients' medical records, clinical features, laboratory data, complications,
      and postoperative hospital admission days. There were no significant intergroup
      differences in patients' medical records, clinical features, or laboratory data,
      except for the number of CBD stones. There were no differences in complications.
      All complications were minor and needed no extra care. The number of
      postoperative hospital admission days showed a significant difference: 18.3 days
      in group PC and 31.5 in group TT. There are so many methods to treat CBD stones
      now that the selection of the procedure can be important for the patient's
      benefit. We prefer primary closure, to get better quality of life postoperatively
      and to avoid further operations and any severe complications.

PMID- 17013714
TI  - The diagnostic efficacy of FDG-PET in the local recurrence of hilar bile duct
      cancer.
AB  - BACKGROUND/PURPOSE: It is frequently difficult to make an accurate diagnosis of
      the local recurrence of hilar bile duct cancer (HBC). We assessed the efficacy of
      fluorodeoxyglucose-positron emission tomography (FDG-PET) in diagnosing the local
      recurrence of HBC. METHODS: Among 18 patients who had previously undergone
      resection of HBC, 5 were suspected of having a recurrence. These 5 patients were
      examined for recurrence by computed tomography (CT) and FDG-PET. A definitive
      diagnosis was determined either by pathological studies or by clinical follow-up.
      RESULTS: Whereas CT showed a recurrent mass in only 1 patient, FDG-PET revealed
      the high uptake of FDG in all patients. Histopathological and/or cytological
      examinations confirmed the local recurrence of HBC in 4 patients. One false
      positive result occurred in a patient with reflux cholangitis. One patient with a
      recurrent tumor was followed by FDG-PET after irradiation therapy. The high level
      of FDG uptake, which had been seen in that patient before irradiation, completely
      disappeared after treatment. CONCLUSIONS: When used in combination with other
      modalities, FDG-PET offered useful information for the diagnosis of a local
      recurrence of HBC. This highly sensitive imaging approach also appeared to be
      useful for follow-up examination after irradiation therapy.

PMID- 17013715
TI  - A survey of the timing and approach to the surgical management of patients with
      acute cholecystitis in Japanese hospitals.
AB  - BACKGROUND/PURPOSE: Despite the fact that there is evidence advocating early
      laparoscopic cholecystectomy for acute cholecystitis (AC), the practice of this
      treatment has not been investigated sufficiently. This study was designed to
      assess the current practice of laparoscopic cholecystectomy for AC among Japanese
      general surgeons. METHODS: A postal questionnaire was sent to the 291 councillors
      of the Japanese Society of Abdominal Emergency Medicine in order to ascertain
      their current management of patients with AC. RESULTS: The response rate was
      72.5%. A policy of early cholecystectomy for AC was adopted by 41.7% of the
      responding surgeons. However, almost the same percentage of surgeons routinely
      managed their patients conservatively, and opted for delayed cholecystectomy at a
      later date. The adoption of laparoscopic cholecystectomy was made by 79.1% of
      surgeons. Laparoscopic cholecystectomy for patients with AC who had percutaneous
      transhepatic gallbladder drainage (PTGBD) was adopted by 73.9% of the surgeons.
      Of the surgeons opting for laparoscopic cholecystectomy, 37.3% performed
      intraoperative cholangiography laparoscopically for all patients with AC.
      CONCLUSIONS: Although early cholecystectomy for patients with AC was not adopted
      by the majority of the surgeons who responded, laparoscopic cholecystectomy was a
      common procedure for early and delayed cholecystectomy. Despite evidence that
      strongly supports the use of early cholecystectomy, the use of this treatment
      remains suboptimal in Japan.

PMID- 17013716
TI  - Genome-wide microsatellite analysis of focal nodular hyperplasia: a strong tool
      for the differential diagnosis of non-neoplastic liver nodule from hepatocellular
      carcinoma.
AB  - Allelic imbalance (AI), which represents certain chromosomal gains or losses, has
      been described in hepatocellular carcinoma (HCC), but the significance of AI
      analysis in focal nodular hyperplasia (FNH) has not been fully clarified. We
      hypothesized, therefore, that comprehensive allelotyping of FNH could be a useful
      tool for differentiating FNH from HCC. A 27-year-old man was admitted to the
      hospital because of general fatigue. A computed tomography (CT) scan disclosed a
      hepatic nodule 8 cm in diameter. No definite diagnosis was made after imaging or
      by biopsy before surgery. Macroscopically and microscopically, the surgical
      specimen showed typical features of FNH. Comprehensive microsatellite analysis
      was carried out with 382 microsatellite markers distributed throughout all
      chromosomes. To detect AI effectively, the cutoff value of the AI index was set
      at 0.70. Among the 382 microsatellite markers, 212 loci were informative, but no
      AI was detected. The absence of gross chromosomal alterations strongly suggested
      that the large nodule was FNH rather than HCC, in terms of its genetic
      background. The patient's subsequent clinical course revealed the nodule to be
      benign. The results suggest that this genome-wide microsatellite analysis is a
      useful tool for the differential diagnosis of non-neoplastic liver nodules from
      HCC.

PMID- 17013717
TI  - Timing of laparoscopic cholecystectomy for subacute calculous cholecystitis:
      early or interval--a prospective study.
AB  - BACKGROUND/PURPOSE: The aim of this prospective study was to evaluate the safety
      and feasibility of early laparoscopic cholecystectomy for subacute cholecystitis
      and to compare it with interval laparoscopic cholecystectomy. METHODS: The study
      was performed in 74 patients who had been diagnosed with subacute cholecystitis
      between January 2000 and June 2005. The patients were divided into two groups.
      The early laparoscopic cholecystectomy group was composed of 31 patients who
      underwent laparoscopic cholecystectomy 24 h after admission to the hospital. The
      interval laparoscopic cholecystectomy group was composed of 43 patients who
      underwent laparoscopic cholecystectomy 8-12 weeks after medical treatment.
      RESULTS: There was no significant difference between the conversion rate,
      intraoperative bleeding, need for intraoperative cholangiography, minor bile duct
      injury, and postoperative complications in the two groups. Eleven patients in the
      interval group underwent urgent laparoscopic cholecystectomy or additional
      procedures because of recurrent cholecystitis, choledocholithiasis, or biliary
      pancreatitis. The early group had a significantly shorter total hospital stay (P
      = 0.031), lower cost of treatment (P = 0.042), and less difficulty with Calot's
      triangle dissection (P = 0.008). CONCLUSIONS: Early laparoscopic cholecystectomy
      can be done without hesitation in patients with subacute cholecystitis, in the
      light of obstacles observed in the interval group, such as dissection difficulty,
      lack of success in "cooling down", and additional problems such as
      choledocholithiasis and biliary pancreatitis.

PMID- 17013718
TI  - Analysis of bile duct injuries (Stewart-Way classification) during laparoscopic
      cholecystectomy.
AB  - In order to investigate mechanisms underlying the occurrence of bile duct
      injuries (BDIs) during laparoscopic cholecystectomy (LC), we analyzed results for
      34 patients (0.59%; 17 men, 17 women; average age, 57 years) with BDI out of 5750
      LCs, based on questionnaire responses from surgical operators, records of direct
      interviews with these operators, operative reports, and videotapes of the
      operations. The indications for LC in the 34 patients were chronic cholecystitis
      in 32 patients and acute cholecystitis in 2. The BDIs in these patients were
      divided into four classes using the Stewart-Way classification: class I, incision
      (incomplete transection) of the common bile duct (CBD), n = 6 (17.6%); class II,
      lateral damage to the common hepatic duct (CHD), n = 9 (26.5%); class III,
      transection of the CBD or CHD, n = 15 (44.1%); and class IV, right hepatic duct
      or right segmental hepatic duct injuries, n = 4 (11.8%). In all class III and 3
      class I cases (18 in total; incidence 53%), the mistake involved misidentifying
      the CBD as the cystic duct. Of all types (classes) of injuries, class III
      injuries showed the mildest gallbladder inflammation, and there was a significant
      (P = 0.0005) difference in the severity of inflammation between class II and III
      injuries. We conclude that complete transection of the CBD, which is rare in
      laparotomy, was the most common BDI pattern occurring during LC and that the
      underlying factor in the operator making this error was mistaking the CBD for the
      cystic duct.

PMID- 17013719
TI  - Role of positron emission tomography in decisions on treatment strategies for
      pancreatic cancer.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to estimate the usefulness of
      positron emission tomography (PET) in deciding on strategies for the treatment of
      pancreatic cancer. The following two parameters were evaluated: the ability of
      PET to provide an estimation of the progression of pancreatic cancer, and the
      ability of PET to predict survival and the effect of chemoradiotherapy. METHODS:
      Forty-two patients underwent PET as part of the procedure for making a diagnosis
      of pancreatic tumors. The maximum standardized uptake value (SUVmax) levels were
      compared with clinicopathological factors and analyzed. RESULTS: PET provided a
      sensitivity of 87%, a specificity of 67%, and an overall accuracy of 85% for the
      diagnosis of pancreatic malignancy. Tumors with distant metastases showed
      significantly higher SUV levels than tumors without metastasis. In the patients
      who received chemoradiotherapy, the overall survival of the group in which SUVmax
      was less than 7.0 was better than that of the group in which SUVmax was more than
      7.0. CONCLUSIONS: We conclude that PET is a useful tool for determining
      pathological status and distant metastasis in pancreatic cancer, and for
      predicting the prognosis of patients receiving chemoradiotherapy.

PMID- 17013720
TI  - Type-2 dominant cytokine gene expression following hepatic surgery.
AB  - BACKGROUND/PURPOSE: Hemorrhage and ischemic liver injuries associated with
      hepatic resection are thought to play a role in postoperative complications,
      possibly through altered cytokine production. The current study was performed to
      investigate the effects of hepatectomy on cytokine gene expression. METHODS: We
      collected blood preoperatively, at completion of operation, and on postoperative
      days 1 and 5 from ten patients undergoing hepatic resection. The peripheral blood
      mononuclear cells were evaluated with real-time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) for gene expression of
      interleukin-10 (IL-10), proinflammatory cytokines (interferon-gamma [IFNgamma],
      IL-15, tumor necrosis factor alpha [TNFalpha], and chemokines regulated on
      activation, normal T expressed and secreted [RANTES], macrophage inflammatory
      protein 1 alpha [MIP-1alpha], [MIP-1beta]). Wilcoxon Rank and paired t-tests were
      used for statistical analysis. RESULTS: Immediately following hepatectomy there
      was a significant (31.4 +/- 60.5-fold; P < 0.05) increase in IL-10 gene
      expression that was sustained until the first postoperative day. In contrast,
      there was a significant downregulation (38 +/- 71 eight fold lower than
      preoperative; P < 0.05) of IFNgamma gene expression on day 1. By postoperative
      day 5, the changes in gene transcript levels of both IL-10 and IFNgamma had
      returned to the preoperative baselines. This contrasting change in IL-10 and
      IFNgamma gene expression in response to hepatic resection was statistically
      significant (P = 0.02). CONCLUSIONS: Hepatectomy elicits an imbalance towards the
      immunosuppressive type-2 cytokine profile in the early postoperative period.
      Measurement of cytokine gene transcripts following hepatic resection may have
      predictive value for clinical outcome, and deserves further study.

PMID- 17013721
TI  - Small-cell neuroendocrine carcinoma of the ampulla of Vater.
AB  - We report a patient (an 80-year-old woman) with anemia and fecal occult blood,
      who had an emergency operation for carcinoma of the cecum (well-differentiated
      adenocarcinoma without local lymph node metastasis). Postoperative magnetic
      resonance cholangiopancreatography, cholangiography, and upper gastroduodenal
      endoscopy showed a tumor of the ampulla of Vater, and pylorus-preserving
      pancreatoduodenectomy was performed. Histology of the resected tumor was that of
      small-cell carcinoma, and immunohistochemistry showed positive staining for
      neuron-specific enolase, chromogranin A, and synaptophysin, confirming the
      neuroendocrine nature of the tumor. As the histology of the tumor was distinct
      from cecal carcinoma, and no tumors were found in other organs, the tumor was
      diagnosed as primary small-cell neuroendocrine carcinoma of the ampulla of Vater.
      The patient died due to multiple liver metastases of the carcinoma of the ampulla
      of Vater 7 months after the pancreatoduodenectomy. The clinical and morphological
      features of this disease have been reported in nine individuals previously.

PMID- 17013722
TI  - Living-donor hepatectomy in right-sided round-ligament liver: importance of
      mapping the anatomy to the left medial segment.
AB  - Left-sided gallbladder (LSGB) and right-sided round ligament (RSRL) are very
      infrequent findings, mostly described in Oriental patients, that have associated
      anatomical variations. An abnormal portal vein branching, mainly to segment IV,
      is strongly associated with RSRL. Living-donor liver transplantation requires
      that both the graft and the remnant liver have adequate vascular supply and
      volumes. Abnormal vascularization of segment IV then threatens this goal. There
      have been scarce reports of the feasibility of living-donor hepatectomy under
      these conditions, all in Oriental populations. We present a case of an Occidental
      living liver donor with RSRL, and discuss the associated anatomical variations of
      the portal vascular supply of the liver, with its implications in planning a
      living-donor hepatectomy.

PMID- 17013723
TI  - Local recurrence at hepaticojejunostomy 9 years after resection of bile duct
      cancer with superficial flat spread.
AB  - We report a male patient aged 45 years, who in 1993 had been diagnosed as having
      middle bile duct cancer and had received a pancreatoduodenectomy. Histopathology
      showed a nodular tumor with the main lesion in the middle bile duct and
      superficial spreading in both proximal and distal directions (which was not
      observed macroscopically), and residual tumor in the epithelium of the cut edge
      near the liver. The patient underwent follow-up without postoperative adjuvant
      therapy. In 2002, 9 years after the operation, the patient developed jaundice and
      was diagnosed with recurrence of bile duct cancer in the anastomotic site, based
      on cholangiographic results. He underwent resection of the right hepatic and
      caudate lobes and the anastomotic region of the bile duct and jejunum.
      Pathological findings showed an invasive tumor in the anastomotic region, with
      continuous intraepithelial spread in the direction of the bile duct, which
      suggested that the residual tumor in the epithelium had grown to become an
      invasive cancer. In this patient, the recurrence required 9 years after
      resection. This case provides evidence for the clinical course that might be
      anticipated for a patient with a residual tumor in the epithelium of the bile
      duct stump and subsequent superficial spreading bile duct cancer.

PMID- 17013724
TI  - Combined chemotherapy of irinotecan and low-dose cisplatin (I/low-P) against
      metastatic biliary tract cancer.
AB  - There is no established or effective standard therapy for metastatic biliary
      tract cancer, resulting in poor prognosis. Recently, we performed combination
      chemotherapy of irinotecan and low-dose cisplatin (I/low-P) for three consecutive
      patients with metastatic biliary tract cancer. The regimen of I/low-P therapy
      consisted of irinotecan (60 mg/m(2)) and low-dose cisplatin (6 mg/m(2)),
      administered by intravenous infusion weekly or biweekly. Of the three patients,
      two showed a partial response, with durations of more than 20 months, and 2
      months, respectively, while the third patient had stable disease for 3 months.
      One patient, who had jaundice, had grade 3 thrombocytopenia, but the other
      patients did not have any severe toxicities. Survival times were more than 20
      months, 10 months, and 13 months, respectively. These outcomes suggest that I/low
      P therapy is safe and may be worth trying as a first-line chemotherapy for
      patients with metastatic biliary tract cancer.

PMID- 17013725
TI  - Undifferentiated spindle-cell carcinoma of the gallbladder: an
      immunohistochemical study.
AB  - A case of undifferentiated spindle-cell carcinoma of the gallbladder is
      described. A 72-year-old man presented with right hypochondralgia and fever.
      Imaging studies revealed a well-demarcated solid tumor (with a necrotic center)
      in the gallbladder that invaded the liver and transverse colon. On gross
      examination of the surgical specimen, the cut surface of the polypoid tumor
      showed nodular invasive growth. Microscopically, the tumor was composed of
      atypical spindle-shaped tumor cells that proliferated in a whirling or
      interlacing pattern. The tumor also showed foci with a malignant epithelial
      component that simulated a carcinosarcoma. Immunohistochemically, the biphasic
      differentiation of the tumor was highlighted by the different immunoreactivity to
      antibodies against cytokeratins, epithelial membrane antigen (EMA), and vimentin
      shown by the malignant epithelial components and the spindle-cell components.
      However the latter showed faint positivity for cytokeratin antibody. These
      results suggested that the spindle-cell carcinoma of the gallbladder originated
      from cholecystic mucosa and showed sarcomatous reaction or dedifferentiation, as
      indicated by the presence of vimentin-positive cells. The proliferation index, as
      detected by ki-67, in the spindle-cell component was higher than that in the
      epithelial component, which may account for the more aggressive biological
      behavior of the spindle-cell component.

PMID- 17013726
TI  - Significance of intraoperative monitoring of arterial blood flow velocity and
      hepatic venous oxygen saturation for performing minimally invasive surgery in a
      patient with multiple calcified pancreaticoduodenal aneurysms with celiac artery
      occlusion.
AB  - Even for patients with multiple pancreaticoduodenal aneurysms, successful
      treatment with noninvasive operative procedures can be employed, if
      intraoperative devices are considered. A 73-year-old man, without any symptoms,
      was admitted to our hospital and had computed tomography (CT) scanning to examine
      his liver for hepatitis C virus (HCV). Selective superior mesenteric artery (SMA)
      angiography confirmed multiple aneurysms in the anterior inferior
      pancreaticoduodenal artery (AIPDA), one aneurysm in the posterior inferior
      mesenteric artery (PIPDA), and another in the occluded celiac trunk, all with
      severe calcification. All of the aneurysms were thought to communicate with each
      other. With the celiac artery occlusion, the right hepatic artery (RHA) was
      revealed to be supplied by collateral arteries from the aneurysms in the AIPDA,
      and the left hepatic artery was shown to be supplied by collaterals from the left
      gastric artery. Intraoperative Doppler echography, at the time of the clamping of
      both IPDAs, demonstrated a marked decrease of blood velocity in all aneurysms
      (before clamping, >50 cm/s; after, <10 cm/s), although loss of pulsation and a
      marked decrease of flow in the RHA were inevitable. Therefore, each of these two
      IPDAs were ligated on the proximal side to the aneurysm, thus preserving the
      blood flow of the pancreas head fed by the PIPDA; bypass grafting from the AIPDA
      to the RHA, using the great saphenous vein, was done at the same time. After the
      creation of an anastomosis, the hepatic venous oxygen saturation (ShvO2)
      increased from 38% (at the time of ligation of the IPDAs) to 57% under
      ventilation. The patient's postoperative clinical course was uneventful. We
      describe and discuss our successful noninvasive operative management of multiple
      pancreaticoduodenal aneurysms, done while monitoring the blood flow and ShvO2,
      with some consideration of the literature.

PMID- 17013727
TI  - Primary peripancreatic lymph node gastrinoma in a woman with MEN1.
AB  - A 39-year-old woman was admitted to hospital due to perforated relapsing duodenal
      ulcer. Clinical, laboratory, and surgical examinations revealed a peripancreatic
      lymph node gastrinoma as the cause of Zollinger-Ellison syndrome. Further
      examinations established multiple endocrine neoplasia type 1 (MEN1) with a
      germline mutation at codon 1153 (T->A) in exon 7, causing an amino-acid change,
      from isoleucine to asparagine (Ile348Asn), in the MEN1 gene. The following
      findings strongly supported a diagnosis of primary lymph node gastrinoma: a rapid
      fall of the serum gastrin level after operation, the continuous normalization of
      the serum gastrin level before and after secretin stimulation, the lack of any
      symptoms, and the absence of another tumor for 13 years after surgical resection
      of the tumor-bearing lymph node. A review of similar cases in the world
      literature reveals that not all gastrinomas in lymph nodes are the result of
      metastastic spread. A long-term symptom-free follow-up after the excision of a
      lymphnode gastrinoma is the only reliable criterion for the diagnosis of a
      primary lymph node tumor. To our knowledge, this is the only well-documented case
      of a primary lymph node gastrinoma in a patient with MEN1. Our case supports the
      idea that any gastrinoma in patients with MEN1 should be surgically resected for
      cure if possible.

PMID- 17013728
TI  - Bilateral hip fractures.
AB  - BACKGROUND: In the past, patients admitted for hip fractures had often sustained
      a contralateral hip fracture. The incidence of bilateral hip fractures has been
      reported to be 5%-10%, and in the future the number of bilateral hip fractures is
      expected to increase with the increase of unilateral hip fractures. We believe
      that bilateral hip fractures can be efficiently prevented if a fracture on the
      other side could be predicted after unilateral hip fracture. Therefore, this
      retrospective study of 835 patients with hip fractures investigated the
      incidence, prognosis, and risk factors of bilateral hip fractures. METHODS: We
      examined 835 hip fractures retrospectively in Japan. Among them, we found 94
      patients with bilateral noncontemporary hip fractures. We investigated age, sex,
      interval between the two fractures, type of fractures, cause, physical
      functioning, and complications. Differences between the unilateral fracture and
      bilateral fractures groups were analyzed statistically for age, sex, and
      complications using Student's t test and the chi-square test. RESULTS: In this
      study, the mean interval between two fractures was 4.28 years, and the second hip
      fracture occurred within 5 years in more than 70% of patients. The type of hip
      fracture was the same in 72.2% of bilateral hip fractures. No difference in age
      and sex was found between the unilateral and the bilateral groups. However,
      concerning complications, 22.1% of patients in the unilateral group and 34.8% in
      the bilateral group had dementia, the difference being significant. CONCLUSIONS:
      These results revealed that the second hip fracture occurred within 5 years of
      the first in more than 70% of bilateral hip fracture patients and that dementia
      is a risk factor of bilateral hip fractures.

PMID- 17013729
TI  - Prevalence, patterns, and risk factors of knee osteoarthritis in Thai monks.
AB  - BACKGROUND: Patterns and risk factors of knee osteoarthritis in Asian countries
      where most people have habitual knee bending activities remain unclear. The
      objective of this study was to evaluate the prevalence, patterns, and risk
      factors of knee osteoarthritis in Thai monks. METHODS: The study was a cross
      sectional survey of monks who lived in temples in southern Thailand.
      Investigations included history, physical examination, and radiographic
      evaluation including weight-bearing antero-posterior, lateral, and skyline views.
      RESULTS: There were 261 monks from 85 temples included in this study. The overall
      prevalence of radiographic knee osteoarthritis was 59.4%, with 29.6% having
      symptomatic radiographic knee osteoarthritis. The patterns of involvement were
      isolated tibiofemoral compartment (7.7%), isolated patellofemoral compartment
      (18.8%), and combined (32.9%). Obesity (OR 5.6, 95% CI; 1.6-19.8), age equal to
      or more than 60 years (OR 3.0, 95% CI; 1.5-6.0), and age at ordainment equal to
      or more than 46 years (OR 2.2, 95% CI; 1.1-4.6) were associated with risk of
      developing radiographic knee osteoarthritis. Obesity (OR 17.9, 95% CI; 2.4-132.1)
      and current smoking (OR 7.7, 95% CI; 2.4-24.3) were associated with symptomatic
      radiographic knee osteoarthritis. Severity of involvement was associated with
      obesity (OR 12.0, 95% CI; 2.3-60.9), older age (OR 3.8, 95% CI; 1.3-5.1), and
      older age at ordainment (OR 2.8, 95% CI; 1.3-6.1). CONCLUSIONS: The prevalence of
      radiographic knee osteoarthritis with patellofemoral involvement in Thai monks is
      high and is more common among the elderly, those who were older at ordainment,
      and obese subgroups. Each pattern of knee osteoarthritis might have a different
      pathomechanism in the development of osteoarthritis.

PMID- 17013730
TI  - Underutilization of antiosteoporotic drugs by orthopedic surgeons for prevention
      of a secondary osteoporotic fracture.
AB  - BACKGROUND: Despite the availability of effective treatment and well-publicized
      treatment guidelines for preventing osteoporotic fractures, there are significant
      gaps in implementing the recommendations, and it is unknown how many patients are
      treated for prevention of secondary osteoporotic fractures. In this study, we
      investigate what percentage of osteoporosis patients were treated with
      antiosteoporotic drugs after osteoporotic fractures of the hip, wrist, and
      proximal humerus, and we discuss here the need for improvement in the treatment
      of osteoporosis following fracture. METHODS: We studied 422 patients with
      osteoporotic fractures, 91 men and 331 women, with an average age of 77.1 years
      (range, 52-102 years). The 422 cases consisted of 299 hip fractures, 97 distal
      radius fractures, and 26 proximal humerus fractures. All patients underwent
      surgical intervention. The variables were examined to ascertain whether
      osteoporosis patients were medicated with antiosteoporotic drugs at postfracture.
      RESULTS: Fifty-five (13%) of the 422 patients received antiosteoporotic
      medication at postfracture. Pharmaceutical treatment was given in 44 cases
      (14.7%) of hip fractures, 8 cases (8.2%) of distal radius fractures, and 3 cases
      (11.5%) of proximal humerus fractures. Thirty-one (7.3% of total) of the 55
      patients were taking the same medication pre- and postfracture. Seven (1.7%) of
      the 55 were administered a different drug compared to before the fracture, and 17
      (4%) started to take an antiosteoporotic drug for the first time subsequent to
      the fracture. CONCLUSIONS: The present rate of treatment is insufficient given
      the high risk of secondary fractures and the availability of appropriate drugs
      that would reduce that risk.

PMID- 17013731
TI  - Thrust plate prosthesis for osteonecrosis of the femoral head: short-term results
      of 15 patients followed 2-6 years.
AB  - BACKGROUND: The thrust plate prosthesis is an implant with a metaphyseal fixation
      at the proximal femur that transmits the load forces of the hip onto the femoral
      neck. METHODS: In this prospective study, 15 patients (8 women, 7 men) with 19
      cementless thrust plate prostheses because of femoral head necrosis were
      examined. A clinical and radiologic evaluation was performed preoperatively, at
      3, 6, 12, 18, and 24 months postoperatively, and every year thereafter. The mean
      follow-up period was 44 (range, 24-72) months. The average age at the time of
      surgery was 49 (27-70) years. The pathogenesis of femoral head necrosis included
      alcoholism (6 joints of 3 cases), Gaucher disease (1 joint of 1 case), Sheehan
      syndrome (2 joints of 1 case), and idiopathic (10 joints of 10 cases). RESULTS:
      The Harris hip score increased from 53 (range, 15-71) to 97 (92-100) points on
      the final evaluation. Although mean preoperative hip flexion and abduction were
      78 degrees (45 degrees -110 degrees ) and 24 degrees (10 degrees -45 degrees ),
      respectively, these increased to 114 degrees (75 degrees -125 degrees ) and 47
      degrees (45 degrees -50 degrees ) 12 months after surgery and remained stable up
      to the latest follow-up. None of the patients displayed mechanical problems, and
      revision was not necessary in any case. CONCLUSIONS: The thrust plate prosthesis
      shows midterm results comparable to those of the cementless stemmed prosthesis
      and supplies advantages, especially for younger patients with femoral head
      necrosis, because of its metaphyseal bone-preserving fixation.

PMID- 17013732
TI  - Dural substitute with polyglycolic acid mesh and fibrin glue for dural repair:
      technical note and preliminary results.
AB  - BACKGROUND: An ideal dural substitute that enables watertight closure, has
      sufficient strength, and can be absorbed without remnant materials that induce
      inflammation, adhesion, and infection is not available. The purpose of this study
      was to evaluate the efficacy of a bioabsorbable polyglycolic acid (PGA) mesh and
      fibrin glue as a substitute for dural repair. METHODS: Altogether, 10 patients
      with noted dural tears during extradural spinal surgery and 20 patients who
      underwent durotomy for intradural spinal surgery were included in this study. In
      a series of 20 consecutive cases, dural closure was performed by suture and
      fibrin glue. In the subsequent 10 consecutive patients, dural closure was
      performed by suture and fibrin glue with the use of absorbable PGA mesh. The
      medical records and magnetic resonance imaging (MRI) of the surgical site were
      retrospectively reviewed to evaluate the presence of a cerebrospinal fluid (CSF)
      fistula or leakage after the surgery. RESULTS: A CSF fistula occurred in five
      patients who underwent dural repair with fibrin glue alone, and postoperative MRI
      showed CSF leakage in two patients with incidental dural tears after laminectomy
      for ossification of ligamentum flavum. No CSF fistula was present in patients who
      underwent dural repair using PGA mesh and fibrin glue, and no adverse effects or
      complications were encountered postoperatively. Follow-up MRI revealed no
      evidence of CSF leakage around the reconstructed dura mater. CONCLUSIONS: The use
      of PGA mesh and fibrin glue for the repair of dura mater is a useful method of
      preventing CSF leakage in spinal surgery.

PMID- 17013733
TI  - Correction and lengthening for deformities of the forearm in multiple
      cartilaginous exostoses.
AB  - BACKGROUND: Multiple cartilaginous exostoses cause various deformities of the
      epiphysis. In exostoses of the ulna, the ulna is shortened and the radius
      acquires varus deformity, which may lead to dislocation of the radial head. In
      this study, we present the results of exostoses resection, with correction and
      lengthening with external fixators for functional and cosmetic improvement, and
      prevention of radial head dislocation. METHODS: We retrospectively reviewed seven
      forearms of seven patients who had deformities of the forearm associated with
      multiple cartilaginous exostoses. One patient had dislocation of the radial head.
      Operative technique was excision of osteochondromas from the distal ulna,
      correction of the radius, and ulnar lengthening with external fixation up to 5 mm
      plus variance. We evaluated radiographs and the range of pronation and
      supination. Furthermore, we conducted a follow-up of ulnar length after the
      operation. RESULTS: Dislocation of the radial head of one patient was naturally
      reduced without any operative intervention. At the most recent follow-up, six of
      the seven patients showed full improvement in pronation-supination. Ulnar
      shortening recurred with skeletal growth of four skeletally immature patients;
      however, it did not recur in one skeletally mature patient. Overlength of 5 mm
      was negated by the recurrence of ulnar shortening about 1.5 years after the
      operation. CONCLUSIONS: We treated seven forearms of seven patients by excision
      of osteochondromas, correction of radii, and gradual lengthening of ulnas with
      external fixators. The results of the procedure were satisfactory, especially for
      function of the elbow and wrist. However, we must consider the possible
      recurrence of ulnar shortening within about 1.5 years during skeletal growth
      periods in immature patients.

PMID- 17013734
TI  - Effects of unipedal standing balance exercise on the prevention of falls and hip
      fracture among clinically defined high-risk elderly individuals: a randomized
      controlled trial.
AB  - BACKGROUND: The aim of this study was to assess the effectiveness of the unipedal
      standing balance exercise for 1 min to prevent falls and hip fractures in high
      risk elderly individuals with a randomized controlled trial. This control study
      was designed as a 6-month intervention trial. SUBJECTS: Subjects included 553
      clinically defined high-risk adults who were living in residences or in the
      community. They were randomized to an exercise group and a control group.
      METHODS: Randomization to the subjects was performed by a table of random
      numbers. A unipedal standing balance exercise with open eyes was performed by
      standing on each leg for 1 min three times per day. As a rule, subjects of the
      exercise group stood on one leg without holding onto any support, but unstable
      subjects were permitted to hold onto a bar during the exercise time. Falls and
      hip fractures were reported by nurses, physical therapists, or facility staff
      with a survey sheet every month. This survey sheet was required every month for
      both groups. RESULTS: Registered subjects were 553 persons ranging in age from 37
      to 102 years (average, 81.6 years of age). Twenty-six subjects dropped out. The
      number of falls and hip fractures for the 6-month period after the trial for 527
      of the 553 subjects for whom related data were available were assessed. The
      exercise group comprised 315 subjects and the control group included 212
      subjects. The cumulative number of falls of the exercise group, with 1 multiple
      faller omitted, was 118, and the control group recorded 121 falls. A significant
      intergroup difference was observed. However, the cumulative number of hip
      fractures was only 1 case in both groups. This difference was not statistically
      significant. CONCLUSIONS: The unipedal standing balance exercise is effective to
      prevent falls but was not shown to be statistically significant in the prevention
      of hip fracture in this study.

PMID- 17013735
TI  - Prediction of acetabular development after closed reduction by overhead traction
      in developmental dysplasia of the hip.
AB  - BACKGROUND: The prediction of acetabular development after reduction of
      developmental dysplasia of the hip (DDH) is important to ensure optimal timing of
      acetabuloplasty and to avoid unnecessary surgery. The objective of this study was
      to find early and reliable predictors of future acetabular dysplasia in the hips
      reduced by overhead traction (OHT). METHODS: We retrospectively reviewed 45 hips
      in 40 patients treated by OHT for DDH without additional procedures. The average
      age at the time of closed reduction was 9.3 months, and the average age at the
      latest examination was 17.3 years. Residual hip dysplasia at skeletal maturity
      was defined according to Severin's classification. The following variables were
      evaluated as possible predictors of the final outcome: age at reduction, severity
      of the dislocation, serial measurements of acetabular index (AI), center-edge
      angle of Wiberg (CE), and the center-head discrepancy distance (CHDD). RESULTS:
      Sixty-two percent of the hips had satisfactory results in Severin I/II and 38%
      had unsatisfactory results in Severin III. Bilateral DDH showed significantly
      poorer outcome than unilateral DDH. The average AI of the unsatisfactory group
      was significantly greater than that of the satisfactory group at 4 years or more
      after reduction. Similarly, the average CE of the satisfactory group was greater
      than that of the unsatisfactory group at 5 years or more after reduction. In
      unilateral cases, the AI and the CE of the uninvolved hip at 1 year after
      reduction also correlated with the final outcome of the involved hip.
      CONCLUSIONS: The AI of 4 years and the CE of 5 years after reduction were the
      earliest predictors of the final outcome. Careful consideration for the need of
      acetabuloplasty would be given at 4 or 5 years after reduction by OHT. Bilateral
      DDH and poor acetabular coverage of the uninvolved hip in unilateral DDH were the
      prognostic factors of unfavorable acetabular development of the dislocated hip.

PMID- 17013736
TI  - Results after operative treatment of transverse acetabular fractures.
AB  - BACKGROUND: Treatment of the transverse acetabular fracture is known to have
      worse results than other fracture types, although this fracture belongs to the
      elementary fracture group. The operative results of the transverse acetabular
      fracture, however, have not been well documented. To determine the results and
      factors that affect the choice of operative treatment for transverse acetabular
      fractures, we retrospectively reviewed 15 cases of transverse fracture. METHODS:
      A total of 15 patients had a transverse fracture, with an average follow-up
      period of 43 months; there were 8 patients with and 7 without a posterior wall
      fracture. There were 11 men and 4 women, with a mean age of 46.6 years. In seven
      cases there was also comminution of the weight-bearing dome. The surgical
      approaches used were the anterior ilioinguinal approach in 4 patients, the
      posterior approach in 10 patients, and the combined approach in 1 patient.
      Postoperative radiographic results were evaluated by Matta's criteria. Final
      clinical results were evaluated by a modified Merle d'Aubigne scoring system.
      RESULTS: All of the fractures healed. The average time for fracture healing was
      17.5 weeks. Postoperative radiology revealed six cases of anatomical reduction,
      five cases of imperfect reduction, and four cases of poor reduction. According to
      the clinical results, nine patients had satisfactory results (three excellent,
      six good), and six had unsatisfactory results (three fair, three poor). Regarding
      complications, there were four cases of traumatic osteoarthritis and three of
      heterotopic ossification. The patients with an anatomical reduction had a higher
      satisfactory result rate. Comminution of the transverse fracture seemed to have
      an adverse influence on the postoperative radiologic result as well as a
      correlation with the development of traumatic arthritis. CONCLUSIONS: Transverse
      acetabular fractures, if not reduced anatomically, may have a tendency toward
      traumatic osteoarthritis and poor clinical outcome. Comminution of the dome may
      portend poor results.

PMID- 17013737
TI  - Middle-term results of simultaneous bilateral femoral osteotomies for advanced
      bilateral coxarthritis.
AB  - BACKGROUND: Osteotomy as a treatment for bilateral osteoarthritis of the hip is
      controversial because of deterioration of the contralateral side. We tried to not
      cause the contralateral hip to deteriorate even more while curing osteoarthritis
      by simple methods (release of iliopsoas and adductor longus muscle tendons and
      lateral transfer of the greater trochanter; Maquet's operation) during the
      rehabilitation period of Pauwels' valgus osteotomy. METHODS: Eighteen patients
      (17 women, 1 man; mean age, 49 years) were indicated for bilateral operations
      performed simultaneously from 1984 to 2001 and followed for more than 3 years
      (mean, 105 months; range, 36-188 months). They were analyzed clinically (hip
      score of Hospital for Special Surgery) and radiographically. Pauwels' valgus
      osteotomy was indicated for 18 hips with or without additional operations.
      Maquet's operation was performed simultaneously on all contralateral sides. Three
      weeks after the operations, the Maquet's operation side was fully weight-bearing
      and the other side was under controlled weight-bearing for 1 year. RESULTS: The
      mean hip score of the valgus osteotomy side was 36 points before the operation
      and 73 points at the final follow-up, respectively; that of Maquet's operation
      side was 44 and 77 points, respectively. Two-thirds (24 of 36) of the hips
      maintained more than 70 points of hip score at the final follow-up. Four hips
      were converted to total hip arthroplasty. Kaplan-Meier survivorship analysis
      revealed that the congruous joint maintained its joint space width for 10 years.
      CONCLUSIONS: Bilateral simultaneous femoral osteotomies for the late stages of
      osteoarthritis could be an alternative to bilateral total hip arthroplasties.

PMID- 17013738
TI  - Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of
      bone marrow-derived mesenchymal stem cells in vitro.
AB  - BACKGROUND: Sonic hedgehog (Shh) protein is known to be an important signaling
      protein in early embryonic development. Also, Shh is involved in the induction of
      early cartilaginous differentiation of mesenchymal cells in the limb and in the
      spine. METHODS: The impact of Shh on adult stem cells, human bone marrow-derived
      mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with
      recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor
      beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on
      cartilaginous differentiation and proliferation were assayed. RESULTS: MSCs when
      treated with either Shh or TGF-beta(1) showed expression of cartilage markers
      aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh
      treated cells showed a very strong cell proliferation and much higher BrdU
      incorporation in cell assay systems. CONCLUSIONS: These are the first data that
      indicate an important role of Shh for the induction of cartilage production by
      MSCs in vitro.

PMID- 17013739
TI  - A new antibacterial carrier of hyaluronic acid gel.
AB  - BACKGROUND: Postoperative infection following total joint arthroplasty is thought
      to be one of the most serious and devastating complications. To develop an
      effective treatment for this complication, we tested a bioabsorbable
      antibacterial carrier that is made from novel cross-linked hyaluronic acid (HA)
      gel and gentamicin (GM). METHODS: Antibacterial activity of the carrier was
      evaluated by the agar diffusion test, direct contact test, in vivo mouse model,
      and in vivo rabbit osteomyelitis model. RESULTS: GM-containing HA gel suppressed
      bacterial growth both in vitro and in vivo. In the rabbit osteomyelitis model,
      beads coated with HA gel containing GM did not disturb bone ongrowth in the
      femoral stem. CONCLUSIONS: Our bioabsorbable carrier of antibiotic-containing HA
      gel is effective for prophylactic treatment or treatment of an actual deep
      infection following total joint arthroplasty.

PMID- 17013740
TI  - Accelerated repair of a bone defect with a synthetic biodegradable bone-inducing
      implant.
AB  - BACKGROUND: Nothing has ever had osteoinductive capacity and degradability
      equivalent to that of autogenous bone, although many types of biomaterials have
      been developed. To address this issue, we constructed a new bone graft substitute
      with osteogenic potential and degradability by using porous beta-tricalcium
      phosphate (beta-TCP) granules, bone morphogenetic protein (BMP), and a synthetic
      block copolymer composed of poly-D: ,L: -lactic acid with randomly inserted p
      dioxanone and polyethylene glycol (PLA-DX-PEG). In this experimental study, the
      bone-inducing capacity and degradation properties of the composite implant during
      the bone healing process were examined in vivo in a cortical and cancellous bone
      defect model in rabbits. METHODS: The advantages of this type of implant have
      been examined in a cortical bone defect model created in the distal femur of
      rabbits. The defects (6.5 x 5 mm) were filled with 30 mg of various implants: BMP
      H [rhBMP-2, 0.0025% (w/w)], BMP-L [rhBMP-2, 0.000625% (w/w)], control A (beta-TCP
      alone), and control B (no implant). The distal femurs were harvested at scheduled
      intervals after surgery and examined for the evaluation of the bony repair of the
      defects by three-dimensional computed tomography and histology. RESULTS: The
      repair of both cortical and cancellous bone occurred predominantly in the BMP-H
      group, and only minor cortical bone repair and cancellous bone formation were
      noted in the BMP-L and control A groups. Most of the beta-TCP was resorbed in the
      BMP-H group at 6 weeks after surgery, whereas a significant amount of beta-TCP
      remained in the BMP-L and control A groups. CONCLUSIONS: beta-TCP granules coated
      with a BMP-retaining synthetic polymer appear to be effective in enhancing the
      repair of both cancellous and cortical bone defects. The early disappearance of
      the implanted beta-TCP and restoration of the normal anatomy of bone tissue are
      two notable features of this approach.

PMID- 17013741
TI  - Evaluation of biodistribution by local versus systemic administration of 99mTc
      labeled pamidronate.
AB  - BACKGROUND: There is an emerging interest in utilizing local and systemic
      administration of bisphosphonates in orthopedics. The primary objective of this
      study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and
      tissue uptake by local versus systemic administration. METHODS: (99m)Tc-PAM was
      administered intravenously (i.v.), subcutaneously (s.c.) and by direct
      application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The
      animals were imaged at 2 h and 24 h after administration and then killed. Organs
      were harvested, and their radioactivity was estimated. Specific uptake in the
      right femur was compared between groups, as was systemic exposure to (99m)Tc PAM.
      RESULTS: Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15
      and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by
      surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than
      the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone
      when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a
      further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h
      of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80%
      ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in
      uptake for the d.a. methods were significantly higher than for the local methods
      at the 24-h time point (P < 0.05). Although renal uptake was comparable with the
      i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was
      significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g)
      (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the
      injected dose at 24 h. CONCLUSIONS: The results indicate that the bone uptake of
      (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake
      significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c.
      method. The findings indicate the need for further study into the potential of
      local administration of bisphosphonates in the presence of orthopedic
      indications.

PMID- 17013742
TI  - Permanent patellar dislocation due to malunion of supracondylar fracture after
      total knee arthroplasty.

PMID- 17013743
TI  - Management of a sacral fracture with neurological injury.

PMID- 17013744
TI  - Unusual benign bone lesion simulating parosteal osteosarcoma.

PMID- 17013745
TI  - Chondromyxoid fibroma of the clavicle.

PMID- 17013746
TI  - Symptomatic cyclops lesion after rupture of the anteromedial bundle of the
      anterior cruciate ligament.

PMID- 17013750
TI  - Expression of cyclooxygenase-2 related to angiogenesis in uterine cervical
      cancers.
AB  - Angiogenesis is essential for development, growth and advancement of solid
      tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various
      tumors. This prompted us to study the clinical implications of COX-2 expression
      related to angiogenesis in uterine cervical cancers. There was a significant
      correlation between microvessel counts and COX-2 levels in uterine cervical
      cancers. COX-2 localized in the cancer cells, but not in the stromal cells of
      uterine cervical cancer tissues. COX-2 levels increased with advancement, and the
      prognosis of the 30 patients with high COX-2 expression in uterine cervical
      cancers was poor (60%), while the 24-month survival rate of the other 30 patients
      with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly
      correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX
      2 might work on angiogenesis in advancement. Therefore, long-term administration
      of COX-2 inhibitors might be effective on the suppression of regrowth or
      recurrence after intensive treatment for advanced uterine cervical cancers.

PMID- 17013747
TI  - Intervertebral disc degeneration: biological and biomechanical factors.

PMID- 17013749
TI  - Aconitase plays a role in regulating resistance to oxidative stress and cell
      death in Arabidopsis and Nicotiana benthamiana.
AB  - In animals, aconitase is a bifunctional protein. When an iron-sulfur cluster is
      present in its catalytic center, aconitase displays enzymatic activity; when this
      cluster is lost, it switches to an RNA-binding protein that regulates the
      translatability or stability of certain transcripts. To investigate the role of
      aconitase in plants, we assessed its ability to bind mRNA. Recombinant aconitase
      failed to bind an iron responsive element (IRE) from the human ferritin gene.
      However, it bound the 5' UTR of the Arabidopsis chloroplastic CuZn superoxide
      dismutase 2 (CSD2) mRNA, and this binding was specific. Arabidopsis aconitase
      knockout (KO) plants were found to have significantly less chlorosis after
      treatment with the superoxide-generating compound, paraquat. This phenotype
      correlated with delayed induction of the antioxidant gene GST1, suggesting that
      these KO lines are more tolerant to oxidative stress. Increased levels of CSD2
      mRNAs were observed in the KO lines, although the level of CSD2 protein was not
      affected. Virus-induced gene silencing (VIGS) of aconitase in Nicotiana
      benthamiana caused a 90% reduction in aconitase activity, stunting, spontaneous
      necrotic lesions, and increased resistance to paraquat. The silenced plants also
      had less cell death after transient co-expression of the AvrPto and Pto proteins
      or the pro-apoptotic protein Bax. Following inoculation with Pseudomonas syringae
      pv. tabaci carrying avrPto, aconitase-silenced N. benthamiana plants expressing
      the Pto transgene displayed a delayed hypersensitive response (HR) and supported
      higher levels of bacterial growth. Disease-associated cell death in N.
      benthamiana inoculated with P. s. pv. tabaci was also reduced. Taken together,
      these results suggest that aconitase plays a role in mediating oxidative stress
      and regulating cell death.

PMID- 17013752
TI  - Myasthenia gravis remission and anti-AChR ab reduction after immunosuppressive
      and anti-neoplastic therapy in a patient with thymic Hodgkin's disease.

PMID- 17013753
TI  - The ACCF/AHA scientific statement on syncope: a document in need of thoughtful
      revision.
AB  - The American College of Cardiology Foundation (ACCF) and the American Heart
      Association (AHA) have recently published, in both the Journal of the American
      College of Cardiology (JACC) and Circulation, a Scientific Statement on the
      Evaluation of Syncope ('Statement'). This Scientific Statement was commissioned
      to provide guidance for clinicians regarding the evaluation of patients who
      present with 'syncope'. The Statement was not intended to be a formal set of
      practice guidelines. However, in the absence of generally accepted practice
      guidelines in North America, the Statement's potential impact on clinical care
      may be more far-reaching than expected; it may erroneously be considered to be
      the authoritative 'de-facto' guideline document. This commentary, submitted by a
      multidisciplinary consortium of more than 60 physicians with expertise in the
      management of transient loss of consciousness (TLOC), points out that in many
      respects the ACCF/AHA Syncope Statement fails to address long-standing clinical
      errors associated with the evaluation of episodes of apparent TLOC, including
      syncope. If not appropriately revised, the current Statement may lead to both
      inadequate patient care as well as a potentially damaging legal environment for
      physicians undertaking evaluation of patients who present with transient loss of
      consciousness.

PMID- 17013754
TI  - Zinc induces ERK-dependent cell death through a specific Ras isoform.
AB  - The effect of Zn on p53-independent cell death was examined in IIC9 embryonic
      fibroblasts. Despite the fact that these cells are p53-minus, Zn-mediated death
      occurs via an apoptotic mechanism. Death is facilitated by the presence of the Zn
      ionophore, pyrithione, indicating that intracellular Zn initiates the death
      response. Our investigations of the mechanism of Zn action demonstrate that Zn
      induces the death of IIC9 cells in a manner that is ERK-dependent. Expression of
      dn-(dominant negative)Ras attenuates ERK1/2 activation by Zn, and correspondingly
      reduces its cytotoxic effects. Raf-RBD pull-down experiments confirm that Zn
      treatment activates Ras and identified H-Ras as the specific isoform activated.
      This contrasts the activation of N-Ras that occurs when IIC9 cells are stimulated
      with thrombin. Thus, although the prolonged activation of the Ras/ERK pathway by
      Zn is similar to that seen when induced by mitogen, the distinguishing feature
      appears to be the isoform specificity of Ras activation.

PMID- 17013755
TI  - Lymph node cells from BALB/c mice with chronic visceral leishmaniasis exhibiting
      cellular anergy and apoptosis: involvement of Ser/Thr phosphatase.
AB  - Visceral leishmaniasis (VL) produced in BALB/c mice through intracardial
      administration of Leishmania donovani amastigotes was accompanied by
      hepatosplenomegaly with high organ parasite load and lymphadenopathy when
      followed up to 4-months or so. To elucidate the mechanism of immunosuppression
      associated with VL, we report here progressive impairment of the proliferative
      response of lymph node cells (lymphocytes) from infected animals (I-LNC) to in
      vitro stimulation with the combination of phorbol 12-myristate 13-acetate (PMA)
      and ionomycin (Io) that could be related to the downregulation of PKC and MAP
      kinase (ERK 1/2) activation process. Further, pretreatment of I-LNC with the
      protein phosphatase inhibitor okadaic acid (OA), but not with calyculin A or
      sodium orthovanadate, significantly restored their proliferative response as well
      as PMA-induced activation of PKC. A population of LNC (primarily T-lymphocytes)
      from chronically infected animals was shown to undergo apoptosis, the number of
      which increased considerably following PMA+ Io stimulation. The apoptotic
      pathway, which was followed through binding of cells to Annexin V, activation of
      caspase-3 and fragmentation of DNA, involved destabilization of mitochondria,
      probably as a result of downregulation of PKC and Bcl-2. Interestingly, prior
      incubation of I-LNC with OA reversed the state of cell cycle arrest (anergy) and
      apoptosis through progression of cells from G0/G1 to S and G2/M phases with
      transcriptional activation of IL-2 and IL-2R genes. Our results suggest that the
      cellular (immune) dysfunction in VL could be attributed to dephosphorylation of
      key molecules in the T-lymphocyte signaling pathway by Ser/Thr phosphatase
      leading to their inactivation.

PMID- 17013756
TI  - Caspase-3 cleaves the formin-homology-domain-containing protein FHOD1 during
      apoptosis to generate a C-terminal fragment that is targeted to the nucleolus.
AB  - The formin homology (FH) proteins play a crucial role in cytoskeleton remodelling
      during many essential processes. In this study, we demonstrate for the first time
      that the formin-homology-domain-containing protein FHOD1 is cleaved by caspase-3
      at the SVPD(616) site during apoptosis. Using confocal microscopy, we further
      demonstrate that while full length FHOD1 is mostly cytoplasmic, the FHOD1 N
      terminal cleavage product is diffusely localized throughout the cytoplasm and the
      nucleoplasm, whereas the C-terminal cleavage product is almost exclusively
      nuclear with some nucleolar localization. Finally, using a run-on transcription
      assay we show that the C-terminal FHOD1 cleavage product has the ability to
      inhibit RNA polymerase I transcription when overexpressed in HeLa cells as shown
      by blockage of BrUTP incorporation.

PMID- 17013757
TI  - 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via
      activation of protein kinase C and JNKs in human leukemia cells.
AB  - In the present study, we found that baicalein (BE), but not its glycoside
      baicalin (BI), induced apoptosis in human leukemia HL-60 and Jurkat cells, but
      not in primary murine peritoneal macrophages (PMs) or human polymorphonuclear
      (PMN) cells, by the MTT assay, LDH release assay, and flow cytometric analysis.
      Activation of the caspase 3, but not caspase 1, enzyme via inducing protein
      processing was detected in BE-induced apoptosis. The ROS-scavenging activity of
      BE was identified by the anti-DPPH radical, DCHF-DA, and in vitro plasmid
      digestion assay, and none of chemical antioxidants including allpurinol (ALL), N
      acetyl-cystein (NAC), and diphenylene iodonium (DPI) affected BE-induced
      apoptosis in HL-60 cells. This suggests that apoptosis induced by BE is
      independent of the production of ROS in HL-60 cells. Interestingly, the apoptotic
      events such as DNA ladders formation and activation of the caspase 3 cascade were
      significantly blocked by TPA addition in the presence of membrane translocation
      of PKCalpha, and TPA-induced protection was reduced by adding the PKC inhibitors,
      GF-109203X and staurosporin. TPA addition induces the phosphorylation of JNKs and
      ERKs, but not p38, protein in HL-60 cells, and incubation of HL-60 cells with
      JNKs inhibitor SP600125, but not ERKs inhibitor, PD98059 or the p38 inhibitor
      SB203580, suppressed the protective effect of TPA against BE-induced apoptotic
      events including DNA ladders, apoptotic bodies, caspase 3 and D4-GDI protein
      cleavage in according with blocking JNKs protein phosphorylation. In addition,
      PKC inhibitor GF-109203X treatment blocks TPA-induced ERKs and JNKs protein
      phosphorylation, which indicates that activation of PKC locates at upstream of
      MAPKs activation in TPA-treated HL-60 cells. Additionally, a loss in
      mitochondrial membrane potential with a reduction in Bcl-2 protein expression,
      the induction of Bad protein phosphorylation, and translocation of cytochrome c
      from mitochondria to the cytosol were observed in BE-treated HL-60 cells, and
      these events were prevented by the addition of TPA. GF-109203X and SP600125
      suppression of TPA against cytochrome c release induced by BE was identified.
      This suggests that activation of PKC and JNKs participate in TPA's prevention of
      BE-induced apoptosis via suppressing mitochondrial dysfunction in HL-60 cells.

PMID- 17013758
TI  - Caspase-3 mediated feedback activation of apical caspases in doxorubicin and TNF
      alpha induced apoptosis.
AB  - Aberrant apoptosis has been associated with the development and therapeutic
      resistance of cancer. Recent studies suggest that caspase
      deficiency/downregulation is frequently detected in different cancers. We have
      previously shown that caspase-3 reconstitution significantly sensitized MCF-7
      cells to doxorubicin and etoposide. In contrast to the well established role of
      caspase-3 as an effector caspase, the focus of this study is to delineate caspase
      3 induced feedback activation of the apical caspases-2, -8, -9 and -10A in
      doxorubicin and TNF-alpha induced apoptosis. Using cell-free systems we show that
      caspases-9 and 2 are the most sensitive, caspase-8 is less sensitive and caspase
      10A is the least sensitive to caspase-3 mediated-cleavage. When apoptosis is
      induced by doxorubicin or TNF-alpha in an intact cell model, cleavage of caspases
      8 and -9, but not caspase-2, was markedly enhanced by caspase-3. Caspase-3
      mediated-feedback and activation of caspase-8 and -9 in MCF-7/C3 cells is further
      supported by an increase in the cleavage of caspase-8 and 9 substrates and
      cytochrome c release. These data indicate that, in addition to its function as an
      effector caspase, caspase-3 plays an important role in maximizing the activation
      of apical caspases and crosstalk between the two major apoptotic pathways. The
      significant impact of caspase-3 on both effector and apical caspases suggests
      that modulation of caspase-3 activity would be a useful approach to overcome drug
      resistance in clinical oncology.

PMID- 17013759
TI  - Proteolysis of HIP during apoptosis occurs within a region similar to the BID
      loop.
AB  - BID is an essential component of many apoptotic pathways. Cytosolic proteases
      cleave BID within an extended loop region, generating an active truncated
      fragment which synergizes with BAX and BAK to induce release of apoptogenic
      factors from mitochondria. To determine whether other proteins are cleaved in a
      similar manner as BID, we performed a database search for proteins which possess
      sequence similarity with the BID loop region. One of the proteins identified was
      the Hsc70-interacting protein (HIP). We analyzed the cleavage pattern of HIP
      using two known activators of BID: granzyme B and caspase-8. In in vitro cleavage
      assays using recombinant proteins, human and rat HIP were cleaved by granzyme B.
      Furthermore, the granzyme B-mediated cleavage site was mapped to the BID loop
      like region of HIP by site-directed mutagenesis. This region was also the target
      for caspase-8-mediated cleavage in rat HIP. However, human HIP was not
      proteolyzed by caspase-8, which probably reflects sequence differences between
      human and rat HIP proteins at the P(1)' position of the caspase-8 recognition
      sequence. To determine whether HIP is cleaved during apoptosis, human Jurkat T
      cells were exposed to granzyme B and perforin. The results of these studies
      suggest that granzyme B-mediated loss of HIP expression occurs in vivo, and in a
      coordinate fashion with loss of BID, pro-caspase-8 and pro-caspase-3. These data
      implicate the Hsp70 co-chaperone HIP in the proteolytic cascade of some apoptotic
      pathways.

PMID- 17013760
TI  - Diverse pathways mediate chemotherapy-induced cell death in acute lymphoblastic
      leukemia cell lines.
AB  - Cancer cell resistance to chemotherapy may be mediated by defects in apoptotic
      pathways. A prior study showed that in vivo apoptosis of Acute Lymphoblastic
      Leukemia (ALL) blasts in response to chemotherapy could occur through diverse
      pathways including both p53-dependent and -independent mechanisms. In this study
      we investigated the apoptotic response in more detail by using a panel of ALL
      cell lines that differed in respect to p53 status. Upon exposure to a uniform
      stimulus, expression of apoptotic proteins, including the effector caspase-3,
      varied among ALL cell lines partly depending on p53 transcriptional activity and
      caspase-8 activation. Although the expression and contribution to apoptosis
      differed among known members of the apoptotic pathway, apoptosis was universally
      mediated by mitochondrial depolarization. The NFkappaB pathway was activated in
      response to chemotherapy but NFkappaB inhibition appeared to not influence
      chemosensitivity. This study further documents the highly variable nature of cell
      death programs in ALL and provides the foundation for cell death pathway
      modulation to improve ALL cure rates without increasing chemotherapy-related
      toxicity.

PMID- 17013761
TI  - Variability in use of cut-off scores and formats on the Edinburgh Postnatal
      Depression Scale: implications for clinical and research practice.
AB  - OBJECTIVES: i) To highlight the increasing use in the literature of unvalidated
      cut-off scores on the Edinburgh Depression Scale (EDS/EPDS), as well as different
      wording and formatting in the scale; ii) to investigate and discuss the possible
      impact of using an unvalidated cut-off score; iii) to highlight possible reasons
      for these 'errors'; and iv) to make recommendations to clinicians and researchers
      who use the EDS/EPDS. METHOD: A convenience sample of studies that have used
      unvalidated cut-off scores, or different formatting, are cited as evidence that
      these types of 'errors' are occurring fairly frequently. Examination of previous
      data from one of the authors is undertaken to determine the effect of using an
      unvalidated cut-off score. SUMMARY: Many studies report rates of high scorers on
      the EDS/EPDS using different cut-off scores to the validated ones. The effect of
      doing this on the overall rate can be substantial. The effect of using different
      formatting is not known, though excluding items from the EDS/EPDS must also make
      a substantial difference. RECOMMENDATIONS: We recommend that i) the validated
      score of 13 or more is used when reporting on probable major depression in
      postnatal English-speaking women, and 15 or more when reporting on antenatal
      English-speaking women; ii) that the wording used is "13 or more" (or
      equivalent), and not other terms that may cause confusion (e.g., '>12'; 'more
      than 12'; '13' etc), iii) if a different cut-off score to the validated one is
      used, a clear explanation is given as to why this has been done; and iv) that the
      scale should be worded and formatted as originally described by its authors.

PMID- 17013762
TI  - A unified hypothesis of coeliac disease with implications for management of
      patients.
AB  - This mini-review presents the research carried out within the context of two of
      the main hypotheses of the aetiology of coeliac disease. The enzymopathic
      hypothesis of the disease has been placed clearly as the underlying deficiency
      causing increased levels of toxic peptides, while the immunological hypothesis
      has been implicated in the pathogenesis of the disorder as the result of the
      action of undigested peptides in the small intestine. As a consequence, we are
      proposing a unified hypothesis of coeliac disease, which takes into account the
      actions of these undigested peptides through their direct cytotoxicity and their
      immunoactivity. At the same time, work aimed at defining some of these
      biologically active peptides, which could be said to be involved in the
      aetiopathogenesis of coeliac disease, will be reported. The review also focusses
      on the use of enzyme therapy for management of the disease, which when used in
      conjunction with the gluten-free diet, offers a safeguard against damage to the
      small intestine caused by small amounts of gluten.

PMID- 17013763
TI  - Protective effect of taurine on respiratory burst activity of polymorphonuclear
      leukocytes in endotoxemia.
AB  - The aim of this study was to evaluate the effect of endotoxin on PMN leukocyte
      respiratory burst activity by measuring G6PD, NADPH oxidase and XO activities in
      guinea pig. In addition, the possible protective role of taurine against
      endotoxin-mediated PMN leukocyte function was examined. All experiments were
      performed with four groups (control, taurine, endotoxemia, taurine plus
      endotoxin) of ten guinea pigs. After the endotoxin was administrated (4 mg/kg)
      both G6PD and NADPH oxidase activities were significantly reduced compared with
      the control group. NADPH oxidase activity returned to the control value and G6PD
      activity also increased but it did not reach the control value. However when
      taurine was administrated (300 mg/kg) the activity of NADPH oxidase reached the
      control value; furthermore, G6PD activity also increased but it could not reach
      to the control value. When taurine was administrated alone, no effect on these
      enzymes was observed. Following the endotoxin administration, the activity of XO
      considerably increased. When taurine was administrated together with endotoxine
      and alone, this activity decreased compared to control value in both conditions.
      These results indicate that the O2*- formation in PMN leukocytes after the
      endotoxin administration is ensured by the catalysis of XO due to the inhibited
      NADPH oxidase activity. It was observed that taurine has considerable anti
      inflammatory and antioxidant effects. However, conflicting results were obtained
      when taurine was administrated alone or together with an oxidant agent.

PMID- 17013767
TI  - Co-occurrence of mental and physical illness in US Latinos.
AB  - BACKGROUND: This study describes the prevalence of comorbid physical and mental
      health problems in a national sample of US Latinos. We examined the co-occurrence
      of anxiety and depression with prevalent physical chronic illnesses in a
      representative sample of Latinos with national origins from Mexico, Cuba, Puerto
      Rico, and other Latin American countries. METHOD: We used data on 2,554 Latinos
      (75.5% response rate) ages 18 years and older from the National Latino and Asian
      American Study (NLAAS). The NLAAS was based on a stratified area probability
      sample design, and the sample came from the 50 states and Washington, DC. Survey
      questionnaires were delivered both in person and over the telephone in English
      and Spanish. Psychiatric disorders were assessed using the World Mental Health
      Survey Initiative version of the World Health Organization Composite
      International Diagnostic Interview (WMH-CIDI). Physical chronic illness was
      assessed by self-reported history. RESULTS: Puerto Ricans had the highest
      prevalence of meeting criteria for any comorbid psychiatric disorder (more than
      one disorder). Puerto Ricans had the highest prevalence (22%) of subject-reported
      asthma history, while Cubans had the highest prevalence (33%) of cardiovascular
      disease. After accounting for age, sex, household income, number of years in the
      US, immigrant status, and anxiety or depression, anxiety was associated with
      diabetes and cardiovascular disease, in the entire sample. Depression and co
      occurring anxiety and depression were positively associated with having a history
      of asthma but not with other physical diseases, in the entire sample.
      Interestingly, Puerto Ricans with a depressive disorder had a lower odds of
      having a history of cardiovascular disease than Puerto Ricans without a
      depressive disorder. The relationship between chronic physical and mental illness
      was not confounded by immigration status or number of years in the US.
      DISCUSSION: Despite previous findings that link acculturation with both chronic
      physical and mental illness, this study does not find that number of years in the
      US nor nativity explain the prevalence of psychiatric-medical comorbidities. This
      study demonstrates the importance of considering psychiatric and medical
      comorbidity among specific ethnic groups, as different patterns emerge than when
      using aggregate ethnic measures. Research is needed on both the pathways and the
      mechanisms of comorbidity for the specific Latino groups.

PMID- 17013768
TI  - Eating disordered behaviors and media exposure.
AB  - BACKGROUND: This study examined this relationship between eating disordered
      behaviors and exposure to ideal-type media in a sample of South African
      university students, who could be expected to have reasonably high levels of
      media exposure. Possible underlying reasons for this complex relationship were
      also investigated. METHOD: It examined the relationship via both quantitative
      (using a questionnaire that included the EAT-26 and a media composite variable)
      and qualitative methods (interviews) in the sample. RESULTS: In the quantitative
      part, sex and level of media exposure significantly predicted scores on the EAT
      26. Women obtained scores that indicated they were more "at risk" for anorexia
      nervosa than men, especially women with higher levels of media exposure. In the
      qualitative part of the study grounded theory was used to explore how this
      relationship was formed. Results indicated that numerous factors, some related to
      the media, predispose women to disordered eating behaviors. The interviewees were
      then more likely to use ideal-type media heavily to sustain their disordered
      eating behaviors. Heavy use of the media led participants to attempt a number of
      strategies to change their appearance to resemble those in the media, with
      various degrees of success. CONCLUSION: The model developed by the qualitative
      research indicated that the media are not necessarily always the cause of
      pathological eating, but that they interact with other factors in the development
      of symptoms of anorexia nervosa for these women.

PMID- 17013769
TI  - Abnormal eating behaviors in adolescent and young adult women from southern
      Brazil: reassessment after four years.
AB  - OBJECTIVE: To investigate whether abnormal eating behaviors in young women could
      predict eating disorders after 4 years. METHOD: 56 women were identified as
      presenting abnormal eating behaviors in a cross-sectional study (Eating Attitudes
      Test-26 and Edinburgh Bulimic Investigation Test). They were matched for age and
      neighborhood to two controls (n = 112). Four years later, they were re-assessed
      with the two screening questionnaires plus the Composite International Diagnostic
      Interview (CIDI 2.1). RESULTS: Women with abnormal eating behaviors at baseline
      showed a high probability of presenting abnormal eating behaviors but it was not
      associated with eating disorders 4 years later. They were also at higher risk for
      obsessive-compulsive disorder, post-traumatic stress disorder, and specific
      phobia. DISCUSSION: Abnormal eating behaviors were related to the maintenance of
      the disturbed behavior over the years, and were associated with increased
      probability for psychiatric diagnoses.

PMID- 17013771
TI  - [Work Group "Textiles": Report on the 12th Meeting of the Work Circle "Health
      evaluation of textile additives and dyes" of the Work Group "Textiles" of the
      Federal Institute for Risk Assessment in Berlin on 8 March 2006].

PMID- 17013770
TI  - [Symposium: Study on Health of Children and Adolescents in Germany].

PMID- 17013772
TI  - [Removal of viruses in water supply treatment -- possibilities of risk
      assessment: results of an International Specialist Symposium in the Environmental
      Department].

PMID- 17013773
TI  - [Can antioxidants prevent atherosclerosis?].
AB  - In vitro studies have shown that antioxidants (e. g. beta-carotene, vitamin C and
      vitamin E) can interfere with some pathomechanisms of atherosclerosis and
      therefore might have a protective effect. From the investigated antioxidants
      vitamin E showed the best effect. Some animal and epidemiological studies
      confirmed such a protective effect in vivo especially after administration of
      high doses of vitamin E. However, most of the placebo-controlled studies for
      primary or secondary prevention failed to show a protective effect even after
      administration of high doses. In addition, other studies demonstrated a risk for
      adverse effects due to antioxidant supplementation (beta-carotene and vitamin E).
      Our review summarises the principle of antioxidant supplementation and a number
      of relevant epidemiological and clinical studies for prevention of
      atherosclerosis. The obtained results suggest that supplementation of
      antioxidants cannot be recommended for the normal population.

PMID- 17013775
TI  - [Toxicogenetics and toxicogenomics. Relevance and application in occupational
      health].
AB  - Xenobiotic metabolising enzymes modify most organic compounds into water soluble
      compounds. Sequence variations of these enzymes can lead to significant
      interindividual differences in the metabolism of xenobiotics. This review covers
      important sequence variations of phase I (cytochrome P450) and phase II
      (glutathion S-transferases, N-acetyltransferases, sulfotransferases, UDP
      glucuronosyl transferases) enzymes and elucidates the significance for
      occupational health. At the present time, the determination of various sequence
      variations is not suitable for an individual risk assessment in occupational
      health.

PMID- 17013774
TI  - [Nutrigenomics. Scientific basis, status and perspectives of application].
AB  - Nutrigenomics investigates the interaction between nutrition and the genome,
      thereby combining nutritional research with functional genomics. Its aims are (1)
      to correlate heterogeneous effects of nutrients with sequence variations in the
      genome and (2) to investigate the effects of nutrients and other food components
      on gene expression at a genome-wide scale (mRNA profiling), and on patterns of
      metabolite alterations in serum (metabolite profiling). The field will provide
      important information as to the biological effects of food components, and to the
      functional consequences of genetic variance. This information will improve the
      prevention of nutrition-related diseases, e. g. by establishing personalised
      nutritional recommendations.

PMID- 17013776
TI  - [State of the art of pharmacogenetic diagnostics in drug therapy].
AB  - Individual differences in the effect and side effect of drugs are partly due to
      genetic factors (genetic polymorphisms). The responsible polymorphisms lie in
      genes encoding for drug metabolism and transport but also in direct and indirect
      drug targets. While genetic variants in pharmacokinetic structures exert effects
      on drug efficacy via the differences in drug exposure, polymorphisms in drug
      targets can directly affect clinical efficacy and may lead to a broad variation
      spectrum between inefficacy and severe side effects. However, at present, our
      knowledge on genetic variants in drug targets is less detailed than the knowledge
      on pharmacogenetic variability within drug metabolism. A goal of pharmacogenetic
      diagnostics implemented in clinical practice is to better predict the individual
      drug effects on the basis of molecular-genetic profiles. Therapy recommendations
      can be given as dose adjustments, in particular in the case of polymorphisms of
      drug metabolizing enzymes which will lead to less variable drug concentrations.
      At present there are few examples of the application of pharmacogenetic tests in
      Germany in order to improve and individualize drug therapy. The reasons for this
      are multifold. On the one hand it is due to the limited awareness of
      pharmacogenetics; on the other hand it may be due to the lack of fast and
      economical availability of the appropriate laboratory tests. The most important
      reason, however, may be that most results of pharmacogenetic research are so far
      not translated into therapeutically usable conclusions and therapy
      recommendations. Thus, testing for a genotype without concrete consequences for
      the drug therapy of an individual patient does not make sense. Pharmacogenetic
      research, thereby, stands in many cases at the threshold to clinical
      applicability and in many cases, for instance for the genotyping for thiopurine
      methyltransferase polymorphisms prior to azathioprine therapy or of
      dihydropyrimidine dehydrogenase polymorphisms prior to treatment with 5
      fluorouracil, as well as for diagnostics of CYP2D6 before therapy with certain
      tricyclic antidepressants and neuroleptics, one would ask already today whether a
      such drug therapy is still responsible without pharmacogenetic diagnostics.

PMID- 17013777
TI  - [Research into the human genome driven by improved methods].
AB  - The enormous progress made by research of the human genome is mainly driven by
      newly established or improved methods for the analysis of nucleic acids and
      proteins. Among the methods that have gained a wide-spread use within a
      comparably short time are fluorescence in situ hybridization (FISH), polymerase
      chain reaction (PCR) including methods for quantitative PCR, and the use of short
      interfering RNA (siRNA) molecules aimed at gene silencing. The increasing
      significance of the analysis of secondary modifications of nucleic acids and
      proteins (genomic imprinting by DNA methylation, posttranslational protein
      modification) is reflected by an increasing use of mass spectrometry for the
      analysis and characterization of these biomolecules. Overall, in the future the
      research into the human genome and the interpretation of data will further
      benefit from these and other refined tools.

PMID- 17013778
TI  - [Genetic diagnosis in medicine. An overview of basic concepts and applications].
AB  - Currently, more than half of all known monogenic diseases are characterized at
      the molecular (DNA) level. This opens the possibility to verify clinically
      suspected disease at the molecular level, to predict future (late-onset)
      disorders, to diagnose many diseases prenatally, and to screen the population for
      genetic traits. Genetic tests that can be performed in Germany, Austria and
      Switzerland are listed in a database maintained by the German Board of Human
      Genetics. As of May 2006, 678 different diseases were amenable to DNA-based
      testing, and 147 institutions offered such tests. The actual genetic test
      utilisation cannot be determined accurately, but can be deduced from the database
      of the "Zentralinstitut der Kassenarztlichen Bundesvereinigung". Data have been
      calculated for the years 1996- 2002. In this time interval, the number of
      individuals undergoing genetic testing doubled approximately every three years.
      The total number in 2002 can be estimated at 220,000.

PMID- 17013779
TI  - [Integration of genetic factors into epidemiological studies].
AB  - During the last two decades, genetic epidemiology has been established in
      parallel to the area of classical epidemiology. This paper presents some
      essentials of the epidemiology of genetic factors. It begins with a discussion of
      complex diseases that are characterized by an involvement of several genes. The
      problems that are attached to modeling gene-gene and gene-environment
      interactions and their integration into causal pathways are elucidated and the
      role of genetic factors in the etiology of complex diseases is investigated.
      Classical and new epidemiological study designs that allow an integration of
      genetic data are introduced. The introduction of this data is partly motivated by
      the danger of bias due to genetic heterogeneity (population stratification) in
      classical designs. The problem of replication of study results is discussed and
      the concept of Mendelian randomization is presented.

PMID- 17013780
TI  - [Genetics in health research and public health].
AB  - Public health practice has to date concerned itself mostly with environmental
      determinants of health and disease and has paid scant attention to genetic
      variations within the population. The advances brought about by genomics is
      changing these perceptions. Many predict that this knowledge will enable health
      promotion messages and disease prevention programmes to be specifically directed
      at susceptible individuals or at subgroups of the population, based on their
      genetic profile. Obviously, the integration of genomics into public health
      research, policy and practice will be one of the most important future challenges
      that our health care systems will face. In this context, Public Health Genomics
      (PHG), defined as the responsible and effective translation of genome-based
      knowledge and technologies into public policy and health services for the benefit
      of population health, will encounter these chances and challenges.

PMID- 17013781
TI  - [Measurement uncertainty in drinking water analysis. Conclusions from
      interlaboratory tests].
AB  - The problems of measurement uncertainty, its estimation and the connection with
      the requirements of the drinking water legislation on the analytical methods are
      described. The difficulties with these requirements are shown. On the basis of
      numerous interlaboratory test data, the concentration dependences of the
      reproducibility standard deviation for 75 drinking water parameters were
      calculated using a variance function described in DIN 38402-45. From this
      function means of standard deviation at the legal limit could be calculated with
      high confidence. These values are compared with the requirements of the
      legislation. These data can be used on the one hand for the estimation of
      uncertainties in the laboratories or the plausibility check of uncertainties
      already estimated. On the other hand these data can be helpful for deriving an
      official interpretation or creating new requirements for the drinking water
      legislation.

PMID- 17013782
TI  - [Prion diseases].
AB  - Prion diseases are one of the paradigms of modern neurological nosology founded
      on molecular grounds. Their incidence is low, however the public health
      challenges derived from their transmissibility, especially due to the appearance
      of a variant of Creutzfeldt-Jakob disease (vCJD) confers them a preferential
      place among health care authority concerns. The evolution of data from the
      European surveillance systems suggests a generalized underdiagnosis of prion
      diseases and casts doubts about their ability to detect a possible second wave of
      atypical vCJD, especially if their clinical-pathological characteristics change.
      Recent data also challenge the feasibility of a subclassification of prion
      diseases according to their genetic-molecular features

PMID- 17013783
TI  - [A descriptive study of intrahospital consultation to a neurological department].
AB  - INTRODUCTION: Intrahospital consultation (IC) is a little analyzed activity
      within daily neurologist hospital care. It entails an extra investment of time
      and resources. This study aims to describe the number and characteristics of the
      IC to a neurological department in our setting and to emphasize its importance
      within daily neurological health care. METHODS: We performed an eighteen-month
      retrospective study of the requests for consultations received during this period
      in the Neurology Service of the Hospital General Universitario. The following
      variables were analyzed: demographic information, number and type of IC, time of
      response, syndromic diagnosis, complementary tests requested and resolution of
      patients. RESULTS: 224 IC in 210 patients were seen. The average time of response
      was 1.57 days, although it was modified because of type of IC (normal: 1.7 days;
      for preference: 1.5 days; urgent: 0.2 days). The specialities that requested most
      consultations were cardiology (12.9%) and internal medicine (12.5 %). The most
      frequent reasons for consultation were: signs and symptoms (27.2%), focal
      neurological deficit (22.8%) and cognitive impairment (17.9%). CT scan and MRI
      were the most common complementary tests. A total of 25.4% of patients were
      referred to neurology outpatient clinic for follow-up. CONCLUSIONS: IC is an
      infrastudied activity in the literature. We consider it necessary to analyze this
      kind of care in every hospital in order to improve the organization and the
      planning of the day-to-day hospital activity

PMID- 17013784
TI  - [Evolution of severe pain associated to spontaneous spinal epidural hematoma].
AB  - INTRODUCTION: Spontaneous spinal epidural hematoma is an infrequent disease,
      whose clinical presentation is very characteristic, with severe pain in region
      corresponding to the metameres affected, which orients its diagnosis and early
      treatment. CLINICAL CASES: Three clinical cases that occurred during 2003 and
      2004 are presented. All three were middle- aged men, with spondyloarthrosis
      signs, posterolateral cervical location of hematoma, which debuted with severe
      cervical and cervicobrachial pain. This was followed by acute onset motor and
      sensory paralysis with spontaneous complete recovery in hours, only the pain
      persisting. The three patients were treated conservatively, pain being the main
      symptom. This pain only responded to intravenous steroids. CONCLUSIONS: The
      evolution of the pain and pathophysiological mechanism by which the corticoids
      could improve the pain associated to these diseases are discussed.

PMID- 17013785
TI  - [Prolonged convulsions treated with buccal midazolam in a setting of mentally
      retarded patients with refractory epilepsy].
AB  - INTRODUCTION: Convulsive status epilepticus is a common major complication of
      epilepsy that results in high morbidity and mortality. Early treatment of
      prolonged seizures with rectal diazepam has been the method of choice in order to
      avoid this complication. However, several randomized trials in recent years
      suggest that buccal midazolam is as effective and safe as rectal diazepam. This
      study aims to seek further confirmation of the efficacy and safety of buccal
      midazolam in daily clinical practice. METHOD: Ten out of 73 adult epileptic
      patients who were residents in a center for people with severe encephalopathy
      were included. We recorded all seizures over a one-year period. Prolonged
      seizures, defined as a seizure lasting one minute or longer, were treated by
      placing buccal midazolam 5 mg (1 ml) between the lower lip and the gum. We
      administered a second dose of midazolam when the seizure lasted more than two
      minutes and a third dose of midazolam, or a combination of rectal diazepam 5 mg
      together with midazolam, as a rescue therapy when the seizure lasted for more
      than 3 minutes. Vital constants were monitored. RESULTS: We treated 52 prolonged
      seizures in 10 patients enrolled in the study. The treatment was effective with a
      single dose within two minutes in 80.7% of seizures. No cardiorespiratory
      complications were detected and no patients presented a convulsive status
      epilepticus. CONCLUSION: Buccal midazolam is effective and safe in the treatment
      of prolonged seizures and has the advantage of being a convenient and socially
      acceptable administration form.

PMID- 17013786
TI  - [Fatal familiar insomnia: clinical, neurophysiological and histopathological
      study of two cases].
AB  - INTRODUCTION: Family prion diseases are caused by mutations in the gene coding
      the prion protein (PrP), originating an altered isoform called prion. One of the
      most uncommon is the fatal familial insomnia (FFI), an entity characterized by
      sleep disorders and that is associated to a mutation in codon 178. METHODS: We
      have studied two male patients, aged 43 and 49 years respectively, from the same
      family. RESULTS: The most significant symptoms were sleep disorders with
      agitation, fractionated sleep, snoring and daytime sleepiness. The evolution was
      brief, the patient dying at a few months of the clinical debut. Sleep registries
      showed destructuration with total loss of the normal cycle of the phases and
      great decrease of the sleep spindles and K complexes in both cases. The
      polygraphy showed tachycardia and apnea pauses. In the molecular study, a
      mutation in the codon 178 was detected, both being methionine/methionine
      homozygotes at position 129. The most outstanding neuropathological abnormalities
      were located in the thalamus with gliosis and neuronal loss of anterior and
      dorsomedial ventral nuclei and also intense neuronal loss in olive of the first
      case. CONCLUSIONS: This study describes two new cases of FFI with genotype D178N
      129M and short course classical phenotype. The polysomnography is essential in
      the diagnostic strategy of this disease whose neuropathological substrate is the
      thalamic alterations and of the inferior olive. Molecular biology permits an
      exact diagnosis of FFI although there is still controversy on the phenotypal
      variability and physiopathogenic mechanisms.

PMID- 17013788
TI  - [Neuroimaging in the diagnosis of human transmissible spongiform
      encephalopathies].
AB  - INTRODUCTION: The role of neuroimaging in the diagnosis of the Human
      Transmissible Spongiform Encephalopathies (HTSE) has been changing from the
      exclusion of other conditions to the contribution of diagnostic data having
      incalculable utility, such as basal ganglia and cerebral cortex in different
      magnetic resonance imaging (MRI) sequences. METHODS: Search in Medline. Reading
      and analysis of related papers. RESULTS: There are alterations such as increased
      of the signals in the caudate nucleus, putamen and cerebral cortex in the
      sporadic Creutzfeldt-Jakob disease (CJD) or increased signal intensity in the
      pulvinar for the variant Creutzfeldt-Jakob disease (vCJD). These signals are
      associated with the molecular subtype in sporadic cases, stage and duration of
      the disease and with pathological findings. CONCLUSIONS: Although magnetic
      resonance imaging (MRI) is only currently included in the vCJD diagnostic
      criteria, it is a useful diagnostic test in the diagnosis of other HTSE,
      especially diffusion-weighted and FLAIR images.

PMID- 17013787
TI  - [Expression and localization of the cellular prion protein (PrPc) in the cow's
      central nervous system. Some reflections on the nvCJD].
AB  - INTRODUCTION: The appearance of bovine spongiform encephalopathy (BSE) and its
      involvement in the generation of the new variant of Creutzfeldt-Jakob Disease
      (nvCJD) had important implications from a social and economical point of view. As
      the presence of PrPC is necessary to establish prion diseases and for the
      replication of PrPSC in BSE, the study of the expression and localization of PrPC
      in the central nervous system of cow, mainly the brainstem, is interesting
      itself. MATERIAL AND METHODS: Expression of PrP by western blot technique and its
      precise localization by immunohistochemistry were analyzed in the central nervous
      system of the autochthonous pyrenees breed, a group of cows with a high incidence
      for BSE. RESULTS: PrP was more abundantly expressed in rostral areas rather than
      caudal regions of the cow brain. Immunohistochemistry was congruent with western
      blotting studies. Localization of PrPC was particularly abundant in the cerebral
      cortex, hippocampus, etc. Noteworthy, immunopositivity was present in the dorsal
      motor nucleus of the vagus and the hypoglossal nucleus. The anterior horn of the
      spinal cord yielded higher labelling for PrP than the posterior horn. CONCLUSION:
      PrPC is more abundantly expressed in rostral areas of the central nervous system.
      According to the findings observed in other mammal species, presence of PrPC in
      motoneurons of cow indicates that PrPSc might be transported from its site of
      entry to the central nervous system following a retrograde direction.

PMID- 17013789
TI  - [Neuroimaging in Creutzfeldt-Jakob's disease].

PMID- 17013790
TI  - [Atypical clinicoradiological course in a case panancephalic variant of
      Creutzfeldt-Jakob].
AB  - INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is the most frequent of the human
      transmissible spongiform encephalopathies. Pathogenic mechanisms of CJD are still
      unknown. Sporadic CJD, the most habitual, is clinically characterized by rapidly
      progressive dementia, myoclonia and ataxia. Panencephalic variant CJD, typically
      from Japan, is characterized by extensive involvement of the cerebral white and
      gray matter. International interest has grown from more than one decade ago in
      relation to the diagnosis of new variant (vCJD). New protocols of MR imaging have
      contributed to the early diagnosis of CJD with specific signs. CASE REPORT: We
      report a case of panencephalic CJD, with atypical clinical presentation and
      unusual MR imaging findings. DISCUSSION: Our patient developed visual and
      psychiatric symptoms. Brain MR imaging showed extensive white matter lesions in
      posterior parietal lobe and occipital regions, which disappeared after steroid
      treatment. The most characteristic radiological sign for sporadic CJD is the high
      signal intensity of the basal ganglia, for vCJD the pulvinar sign and, for
      panencephalic CJD the presence of periventricular white matter lesions, with
      tendency to the spread when the disease progress. In serial MR imaging studies of
      our patient, we could see how typical signs were appearing. However, the complete
      and unusual resolution of the original white matter lesions makes us to think
      about a possible inflammatory component, in some time in the evolution of white
      matter damage.

PMID- 17013791
TI  - [MM1 variant of sporadic Creutzfeldt-Jakob disease with long duration akinetic
      mutism state].
AB  - INTRODUCTION: When patients present with a characteristic clinical picture of
      Creutzfeldt-Jakob disease (CJD) associated with positive 14-3-3 assay, periodic
      sharp wave complexes, high-signal of the striatum on magnetic resonance imaging,
      and homozygosis methionine (M) in codon 129, the median survival is 4 to 6
      months. CLINICAL CASE: We report a 58-year-old woman with these typical features
      who survived 21 months, 19 of them in an akinetic mutism state. The autopsy
      confirmed the diagnosis of the most common CJD phenotype (MM1), usually
      associated with a shorter survival, and demyleinitation of the white matter
      (panencephalopathic form). CONCLUSIONS: The MM1 variant of CJD, with a rapidly
      progressive course leading into an akinetic mutism shortly after disease onset
      can be followed by a long akinetic mutism state. This profile is suggestive of
      panencephalopathic form and should be taken into account when counselling about
      survival.

PMID- 17013792
TI  - [Adult-onset ataxia-telangiectasia. A clinical and therapeutic observation].
AB  - A case of adult-onset ataxia-telangiectasia (AT) is presented, with debut at the
      age of 18 years and survival into the fourth decade. The clinical picture
      included cerebellar ataxia, distal weakness and hypopalesthesia in the lower
      limbs, oculomotor apraxia, dysarthria, and conjunctival telangiectasiae.
      Carcinoembrionic antigen was raised in plasma. MR imaging showed atrophy of the
      cerebellar vermis and thinning of the spinal cord. Deficiencies of gamma
      aminobutyric acid and glutamate have been found in the cerebellar cortex in a
      case of AT. These were attributed to the loss of Purkinje cells and granule
      cells. In spite of some ataxias having improved with the gabaergic drugs
      gabapentin and tiagabine, the administration of gabapentin, acetazolamide and a
      placebo, did not benefit this patient. Pregabalin, 225 mg/day, ameliorated the
      ataxia unexpectedly, with further improvement after the addition of tiagabine.
      The authors suggest that the beneficial effect observed might have been due,
      either to the higher affinity of pregabalin towards alpha2-delta, a subtype of
      the alpha2-delta subunit which forms part of the voltage-gated calcium channel;
      either to the profusion of this subtype in the Purkinje cell layer, or to its
      larger capacity to let calcium into the neuron; or to the combination of these.
      These differences with gabapentin could explain the higher power of pregabalin in
      the stimulation of the cerebellar structures, thus justifying the improvement of
      ataxia in this case of AT. A synergistic effect with pregabalin is proposed as
      the cause of the improvement obtained with the addition of tiagabine.

PMID- 17013793
TI  - [Subcutaneous histamine for preventive treatment of migraine?].

PMID- 17013794
TI  - Clinical utility of determination of HER-2/neu and EGFR fragments in serum of
      patients with metastatic breast cancer.
AB  - INTRODUCTION: The growth factor receptors EGFR and HER-2/neu are targets for new
      treatment strategies and are of potential use as prognostic and predictive
      factors. However, the optimal method of determination in order to obtain
      clinically relevant information remains a source of controversy. METHODS: HER
      2/neu and EGFR expression was examined by immunohistochemistry in primary tumors
      of patients with breast cancer. In addition, serum was tested for the
      extracellular domains of HER-2/neu (HER-2/neu ECD) and EGFR (sEGFR) before
      initiation of therapy for metastatic disease (n=76). The course of disease from
      the time of metastasis with regard to these parameters was evaluated by
      univariate and multivariate analyses. RESULTS: HER-2/neu ECD levels at the time
      of metastatic disease were correlated with HER-2/neu expression determined by
      immunohistochemistry from primary tumors (p=0.001). No correlation was observed
      between expression of EGFR in primary tumors and sEGFR serum levels. HER-2/neu
      ECD and sEGFR levels at the onset of metastatic disease did not show a
      significant impact on overall survival. CONCLUSIONS: Determination of HER-2/neu
      ECD levels in the serum measured by ELISA at the onset of metastatic disease
      could offer an alternative to immunohistochemistry of the primary tumor since
      serum levels are correlated with protein expression in primary tumors. In
      contrast, no such correlation was observed for EGFR.

PMID- 17013795
TI  - Pre-treatment prediction of chemoresistance in second-line chemotherapy of
      ovarian carcinoma: value of serological tumor marker determination (tetranectin,
      YKL-40, CASA, CA 125).
AB  - OBJECTIVE: To examine if the determination of the levels of serological tumor
      markers at time of relapse had any predictive value for chemoresistance in the
      second-line treatment of ovarian cancer patients. METHODS: From a registry of
      consecutive single-institution patients with epithelial ovarian carcinoma
      pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid
      tumor recurrence, and (b) second-line chemotherapy consisting of topotecan
      (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive
      disease). Stored serum samples were analyzed for the biochemical tumor markers
      tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The
      serum tumor marker levels at time of relapse were correlated with response status
      at landmark time after 4 cycles of second-line chemotherapy. Univariate and
      multivariate logistic regression analyses (chemoresistant vs non-chemoresistant
      disease) were performed. RESULTS: At landmark time, 26% of patients had
      progression according to the GCIG (Gynecologic Cancer Intergroup) progression
      criteria. In univariate logistic regression analysis, the tumor markers
      tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3;
      p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for
      second-line chemoresistance, whereas serum CA 125 had no predictive value. In a
      multivariate logistic regression analysis, serum tetranectin and CASA both had
      independent predictive value for chemoresistance. The combined determination of
      tetranectin and CASA had a specificity of 90% with 33% sensitivity for the
      prediction of chemoresistance (area under the receiver operating characteristic
      curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of
      tetranectin, or high serum levels of CASA or YKL-40, are associated with
      increased risk of second-line chemoresistance in patients with ovarian cancer.

PMID- 17013796
TI  - HPV testing and Pap test: role for a combined approach in a non-screened
      population.
AB  - The aim of the present study was to test the polymerase chain reaction (PCR) as a
      tool to identify human papillomavirus (HPV) in routine cytological samples
      scraped from the uterine cervix. Moreover, attention has been focused on the
      correlation between HPV types and early intraepithelial lesions. The study
      involved 586 women who had undergone conventional Pap test. Analysis of HPV
      infection was performed by PCR and HPV typing by dot blot. In a group of 78 cases
      histologically diagnosed as high-grade squamous intraepithelial lesions (HSILs),
      the cytological diagnosis was correct in 92.3% and the HPV test was positive in
      89.8% of cases; combined positivity at Pap and/or HPV tests raised this figure to
      99.0%. In a group of 67 cases histologically diagnosed as low-grade squamous
      intraepithelial lesions (LSILs), the cytological diagnosis was correct in 73.1%
      and the PCR-based HPV test was positive in 64.2%; combined positivity at Pap
      and/or HPV tests raised this figure to 91.0%. This study confirms the limitations
      of screening programs based on Pap test only. Our results suggest, in fact, that
      adding the HPV test to primary screening could increase the yield of preinvasive
      cervical lesions.

PMID- 17013797
TI  - Evaluation of diagnostic accuracy of screening by fecal occult blood testing
      (FOBT). Comparison of FOB Gold and OC Sensor assays in a consecutive prospective
      screening series.
AB  - We evaluated a new immunological fecal occult blood testing assay (FOB Gold,
      Sentinel = SENT) compared to the assay currently employed in the Florence
      screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were
      screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb
      cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131
      (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with
      SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with
      SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and
      28.2% for SENT and the specificity was 97.7 for both. The differences were not
      statistically significant. Adding SENT to OC increased the positivity rate by 32%
      and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both
      tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they
      differed on different tubes but not on the same tube, suggesting inhomogeneous Hb
      content or varying fecal matrix influence in different samples. SENT has
      practical advantages for screening [corrected] (fully automated, high output,
      requires no dedicated instrument), a comparable specificity and a lower
      sensitivity, though the latter difference may be partially ascribed to
      differences in sampling and not to the assay itself [corrected] Because of the
      statistical insignificance of the differences, further studies are needed for
      confirmation.

PMID- 17013798
TI  - Is the urokinase-type plasminogen activator system a reliable prognostic factor
      in gastric cancer?
AB  - AIM: The aim of this prospective study was to evaluate the clinical and
      prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients
      with gastric cancer. METHODS: This prospective study analyzed specimens obtained
      from 105 gastric cancer patients who underwent gastrectomy with extended
      lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied
      semiquantitatively in the tumor epithelium and was correlated with the
      clinicopathological features of each patient. RESULTS: Univariate analysis
      revealed no statistically significant association of uPA levels with pT and pN
      category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor
      invasion (p=0.665), UICC classification (p=0.21) and the Lauren classification
      (p=0.578). PAI-1 expression showed no statistically significant correlation with
      pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading
      (p=0.273), and the Lauren classification (p=0.368). Only the UICC classification
      was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed
      no significant association of uPA and PAI-1 with overall survival (p=0.0929 and
      0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic
      value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the
      uPA-system as a biologically defined prognostic marker to identify high-risk
      gastric cancers should be applied with caution. However, considering the number
      of patients involved and the borderline level of significance observed in this
      study, a larger number of events may have resulted in significant differences.

PMID- 17013799
TI  - Prognostic value of carcinoma-associated antigen MK-1 in urinary bladder
      carcinoma.
AB  - BACKGROUND: The present study has been performed to evaluate the expression of MK
      1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder
      and to correlate this new marker with the conventional histopathological
      parameters. PATIENTS AND METHODS: Paraffin sections of 5-microm thickness from 81
      cases were prepared for hematoxylin and eosin staining and immunohistochemical
      analysis of MK-1 expression was carried out. RESULTS: Forty-six cases (56.8%)
      were positive for MK-1 protein expression. Significant correlations between MK-1
      expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy
      (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade,
      stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to
      outcome. Univariate and multivariate analysis of survival were performed. The
      overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression,
      tumor grade, DNA ploidy, and recurrence had a significant impact on the survival
      of these patients. In a Cox proportional hazards model, recurrence maintained its
      significant impact on survival. CONCLUSIONS: These findings suggest that MK-1 is
      a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were
      positive for MK-1 expression. However, only recurrence was an independent
      prognostic factor in patients with schistosomiasis- associated squamous cell
      carcinoma of the bladder.

PMID- 17013800
TI  - Stat3 expression in oral squamous cell carcinoma: association with
      clinicopathological parameters and survival.
AB  - The present study sought to explore the occurrence of signal transducer and
      activator of transcription 3 (Stat3) in patients with oral squamous cell
      carcinoma (n=135) and its potential relationship with clinicopathological
      parameters and survival. Stat3 expression was studied by immunohistochemistry.
      Cytoplasmic or nuclear localization of Stat3 was observed in 62% of patients,
      whereas only nuclear Stat3 expression was found in 44%. Stat3 positivity in early
      stage patients was 45% compared to 79% in advanced-stage patients. However, early
      stage Stat3-positive patients showed a gradual increase in staining intensity,
      with intense staining seen in 52% of the tumors compared to 18% in Stat3-positive
      advanced-stage patients, where a gradual decrease in intensity expression was
      observed (p=0.001). Stat3 showed a significant positive correlation with disease
      stage (p=0.001), nodal status (p=0.033) and tumor size (p=0.001). Multivariate
      survival analysis using the Cox proportional hazard regression model showed that
      nuclear Stat3 was a significant independent prognosticator for both relapse-free
      survival (p=0.014) and overall survival (p=0.042) in early-stage patients. Our
      results indicated that Stat3 activation is an early event in oral squamous cell
      carcinoma and represents a potential risk factor for poor prognosis in early
      stage patients.

PMID- 17013801
TI  - Mutations in exons 6 and 7 of TP53 gene correlate positively with serum tumor
      necrosis factor alpha independent of microsatellite instability in BAT26 gene in
      Egyptian patients with endometrial carcinoma.
AB  - Abnormalities in the TP53 gene are the most frequent genetic alterations in human
      cancers. The role and mechanism of TP53 mutations have been well studied in many
      types of human cancer. Similarly, the presence of microsatellite instability
      (MSI) in the DNA mismatch repair system (hMSH2) may provide evidence of faulty
      DNA mismatch repair. One of the most important locations of MSI is the BAT26
      gene. In addition, deranged serum cytokines, especially elevated levels of the
      tumor necrosis factor (TNF) alpha, have been found in many gynecological
      conditions. AIMS: The current study aimed at evaluating mutations in exons 6 and
      7 of TP53 and the presence of microsatellite instability in BAT26 of the hMSH2
      system in Egyptian patients with endometrial carcinoma. The study also evaluated
      whether there was a correlation between any of these genetic
      mutations/instability and the tissue expression of estrogen and progesterone
      receptors and the serum TNF-alpha level. PATIENTS AND METHODS: The current study
      included 2 groups: a control group comprising 20 healthy women aged 52.21 +/-
      5.80 years attending the clinic for routine checkups and 40 patients with
      endometrial cancer aged 55.30 +/- 6.21 years. Mutations in TP53 and BAT26 were
      evaluated using polymerase chain reaction-single-strand conformational
      polymorphism (PCR-SSCP) and automated sequencing while serum TNF-alpha was
      measured using an ELISA technique. Estrogen and progesterone receptor expression
      in biopsy tissue was evaluated using immunohistochemical staining. RESULTS: Seven
      of the 40 patients (17.5%) were positive for TP53 gene alterations in exon 6,
      while 9 patients (22.5%) were positive for TP53 alterations in exon 7. Cases
      positive for TP53 mutations had higher tumor stages. Ten patients (25%) showed
      MSI in BAT26. Nearly all patients with mutations in BAT26 had a strong family
      history for endometrial cancer (chi2=13.33, p<0.05). There was no positive
      correlation between the presence of MSI in the BAT26 gene and mutations in the
      TP53 gene or high serum TNF-alpha levels. Cases positive for TP53 mutations had a
      significantly higher level of TNF-alpha than cases negative for TP53 mutations
      (p<0.05). Cases showing mutations in exon 6 or 7 of TP53 showed a significantly
      higher intensity of immunohistochemical staining for estrogen and progesterone
      receptor expression in biopsy tissue than cases negative for mutations.
      (chi2=8.11, p<0.05). CONCLUSION: Our results suggest that the development of
      endometrial carcinoma is probably mediated through a multi-step carcinogenesis
      pathway and mutation of TP53 does not necessarily result from the presence of
      microsatellite instability in BAT26. The high serum TNF-alpha levels detected in
      our patients may represent an immunological antitumor response that was
      particularly evident in cases positive for TP53 mutations.

PMID- 17013802
TI  - Urinary neopterin in patients with advanced colorectal carcinoma.
AB  - In previous studies, mostly in patients with early stage colorectal carcinoma,
      neopterin, an indicator of systemic immune activation, has been associated with
      poor prognosis. The aim of the present study was to evaluate urinary neopterin in
      patients with advanced or metastatic colorectal carcinoma treated with
      chemotherapy. A retrospective analysis was performed of urinary neopterin,
      determined by high-performance liquid chromatography, in 88 patients with
      advanced or metastatic colorectal carcinoma. Peripheral blood cell count and
      serum carcinoembryonic antigen (CEA) were determined in 72 patients before the
      start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was
      significantly increased compared to controls, but lower than in patients with
      inflammatory bowel disease. Neopterin correlated significantly with serum CEA,
      age, peripheral blood leukocyte and platelet counts. The median survival of
      colorectal carcinoma patients with urinary neopterin below 214 micromol/mol
      creatinine was significantly longer compared to that of patients with higher
      neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and
      hemoglobin were also associated with survival in univariate analysis, but in
      multivariate analysis only urinary neopterin and serum CEA were independent
      predictors of survival. High urinary neopterin during follow-up was also
      predictive of poor prognosis.

PMID- 17013803
TI  - Total synthesis of platensimycin.

PMID- 17013806
TI  - Interferon-gamma differentially regulates TGF-beta1 and TGF-beta2 expression in
      human retinal pigment epithelial cells through JAK-STAT pathway.
AB  - Retinal pigment epithelium (RPE) and transforming growth factor-beta (TGF-beta)
      have been shown to be involved in various retinal diseases. We have studied the
      role of inflammatory cytokines on the expression and secretion of TGF-beta in
      human RPE cells (HRPE). Confluent cultures of HRPE derived from donor eyes were
      used. RT-PCR analyses showed that TNF-alpha and IL-1beta increased the mRNA
      levels of both TGF-beta1 and TGF-beta2. IFN-gamma enhanced constitutively
      expressed, as well as, TNF-alpha-and IL-1beta-induced TGF-beta1 mRNA levels but
      decreased TGF-beta2 mRNA. The effects of these cytokines on TGF-beta1 and TGF
      beta2 secretion correlated with the mRNA levels. TGF-beta1 was always produced as
      the latent form while 21-31% of TGF-beta2 was in the active form. IFN-gamma
      reduced the production of active form of TGF-beta2 to 4-9%. TGF-beta3 secretion
      was not detectable under any of the conditions. The Real-Time PCR analysis of TGF
      beta mRNAs confirmed the observed results. The TGF-beta1 and TGF-beta2 secretion
      was induced by TGF-beta2 and TGF-beta1, respectively. Under these conditions, the
      contrasting effects of IFN-gamma on TGF-beta1 and TGF-beta2 secretion were also
      observed. JAK inhibitor selectively inhibited IFN-gamma induced TGF-beta1
      secretion and mRNA levels while reversing the inhibitory effects of IFN-gamma on
      TGF-beta2. Analyses of transcription factor activity strongly indicated the role
      of STAT-1 but not NFkappaB, C-Myc, C-Jun, SP-1, MEF-2. Our data demonstrate that
      IFN-gamma differentially regulates constitutively expressed, as well as, cytokine
      induced TGF-beta1 and TGF-beta2 mRNA levels and secretion of TGF-betas by HRPE.

PMID- 17013807
TI  - Opposite effect of corticosteroids and long-acting beta(2)-agonists on serum- and
      TGF-beta(1)-induced extracellular matrix deposition by primary human lung
      fibroblasts.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are characterized by
      chronic airway inflammation and major structural lung tissue changes including
      increased extracellular matrix (ECM) deposition. Inhaled corticosteroids and long
      acting beta(2)-agonists (LABA) are the basic treatment for both diseases, but
      their effect on airway remodeling remains unclear. In this study, we investigated
      the effect of corticosteroids and LABA, alone or in combination, on total ECM and
      collagen deposition, gene expression, cell proliferation, and IL-6, IL-8, and TGF
      beta(1) levels by primary human lung fibroblasts. In our model, fibroblasts in
      0.3% albumin represented a non-inflammatory condition and stimulation with 5% FCS
      and/or TGF-beta(1) mimicked an inflammatory environment with activation of tissue
      repair. FCS (5%) increased total ECM, collagen deposition, cell proliferation,
      and IL-6, IL-8, and TGF-beta(1) levels. In 0.3% albumin, corticosteroids reduced
      total ECM and collagen deposition, involving the glucocorticoid receptor (GR) and
      downregulation of collagen, heat shock protein 47 (Hsp47), and Fli1 mRNA
      expression. In 5% FCS, corticosteroids increased ECM deposition, involving
      upregulation of COL4A1 and CTGF mRNA expression. LABA reduced total ECM and
      collagen deposition under all conditions partly via the beta(2)-adrenergic
      receptor. In combination, the drugs had an additive effect in the presence or
      absence of TGF-beta(1) further decreasing ECM deposition in 0.3% albumin whereas
      counteracting each other in 5% FCS. These data suggest that the effect of
      corticosteroids, but not of LABA, on ECM deposition by fibroblasts is altered by
      serum. These findings imply that as soon as airway inflammation is resolved, long
      term treatment with combined drugs may beneficially reduce pathological tissue
      remodeling.

PMID- 17013808
TI  - Cyclin A but not cyclin D1 is essential for c-myc-modulated cell-cycle
      progression.
AB  - The proto-oncogene c-myc is a key player in cell-cycle regulation and is
      deregulated in a broad range of human cancers and cell proliferation disorders.
      Here we reported that overexpression of c-myc in human embryonic lung fibroblasts
      (HEL) that have low endogenous c-myc enriched S phase cells with increased
      expression of cyclin D3, E, A, Cdk2, and Cdk4, and decreased expression of p21
      and p27. To the opposite, using RNAi to downregulate c-myc expression in A549
      cells that have high endogenous c-myc enriched G1 phase cells with decreased
      expression of cyclin D3, E, A, Cdk2, Cdk4, and increased expression of p21 and
      p27. We found that cyclin A expression was the most susceptive to changes in c
      myc levels and essential in c-myc-modulated cell cycle pathway via co
      transfection, however, cyclin D1 showed no change between treated and control
      groups in either HEL or A549 cells. Our results indicated that upregulation of c
      myc expression promotes cell cycling in HEL cells, whereas downregulation of c
      myc expression causes G1 phase arrest in A549 cells, and the c-myc-mediated cell
      cycle regulation pathway was dependent on cyclin A and involved cyclin D3, E,
      Cdk2, Cdk4, p21, and p27, but not cyclin D1.

PMID- 17013809
TI  - The evolution of progesterone receptor ligands.
AB  - Progesterone is one of the first nuclear receptor hormones to be described
      functionally and subsequently approached as a drug target. Because progesterone
      (1) affects both menstruation and gestation via the progesterone receptor (PR),
      research aimed at modulating its activity is usually surrounded by controversy.
      However, ligands for PR were developed into drugs, and their evolution can be
      crudely divided into three periods: (1) drug-like steroids that mimic the
      gestational properties of progesterone; (2) drug-like steroids with different
      properties from progesterone and expanded therapeutic applications; and (3) non
      steroidal PR ligands with improved selectivity and modulator properties and
      further expanded therapeutic applications. Although the latter have yet to see
      widespread clinical applications, their development is founded on a half century
      of research, and they represent the future for this drug target.

PMID- 17013810
TI  - beta-Nerve growth factor participates in an auto/paracrine pathway of regulation
      of the meiotic differentiation of rat spermatocytes.
AB  - NGF appears to be involved in spermatogenesis. However, mice lacking NGF or TrkA
      genes do not survive more than a few days whereas p75(NTR) knockout mice are
      viable and fertile. Therefore, we addressed the effect of betaNGF on
      spermatogenesis by using the systems of rat germ cell culture we established
      previously. betaNGF did not modify the number of Sertoli cells, pachytene
      spermatocytes, secondary spermatocytes nor the half-life of round spermatids, but
      increased the number of secondary meiotic metaphases and decreased the number of
      round spermatids formed in vitro. These effects of betaNGF were reversible and
      maximal at about 4 x 10(-11) M. Conversely, K252a, a Trk-specific kinase
      inhibitor, enhanced the number of round spermatids above that of control
      cultures. The presence of betaNGF and its receptors TrkA and p75(NTR) was
      investigated in testis sections, in Sertoli cell and germ cell fractions, and in
      germ cell and Sertoli cell co-cultures. betaNGF was detected only in germ cells
      from pachytene spermatocytes of stages VII up to spermatids of stages IX-X. TrkA
      and p75(NTR) were detected in Sertoli cells and in these germ cells. Taken
      together, these results indicate that betaNGF should participate in an
      auto/paracrine pathway of regulation of the second meiotic division of rat
      spermatocytes in vivo.

PMID- 17013811
TI  - Desensitization of GABA(B) receptor signaling by formation of protein complexes
      of GABA(B2) subunit with GRK4 or GRK5.
AB  - We investigated the role of G protein coupled-receptor kinases (GRKs) in the
      desensitization of GABA(B) receptor-mediated signaling using Xenopus oocytes and
      baby hamster kidney (BHK) cells. Baclofen elicited inward K(+) currents in
      oocytes coexpressing heterodimeric GABA(B) receptor, GABA(B1a) subunit (GB(1a)R)
      and GABA(B2) subunit (GB(2)R), together with G protein-activated inwardly
      rectifying K(+) channels (GIRKs), in a concentration-dependent manner. Repetitive
      application of baclofen to oocytes coexpressing GABA(B)R and GIRKs did not change
      peak K(+) currents in the first and second responses, but the latter responses
      were significantly attenuated by coexpression of either GRK4 or GRK5 with
      attenuation efficacy of GRK4 > GRK5. Coexpression of other GRKs including GRK2,
      GRK3, and GRK6 had no effect on GABA(B) receptor-mediated desensitization
      processes. In BHK cells coexpressing GRK4 fused to Venus (brighter variant of
      yellow fluorescent protein, GRK4-Venus) with GB(1a)R and GB(2)R, GRK4-Venus was
      expressed in the cytosol but was translocated to the plasma membranes by GABA(B)R
      activation. In BHK cells coexpressing GRK4 fused to Cerulean (brighter variant of
      cyan fluorescent protein, GRK4-Cerulean) with GB(1a)R and GB(2)R-Venus,
      fluorescence resonance energy transfer (FRET) analysis demonstrated that GRK4
      Cerulean formed a protein complex with GB(2)R-Venus. Immunoprecipitation and
      Western blot analysis confirmed GB(2)R-GRK4 complex formation. GRK5 also formed a
      complex with GB(2)R on the plasma membranes as determined by FRET and Western
      blotting but not GRK2, GRK3, and GRK6. Our results indicate that GRK4 and GRK5
      desensitize GABA(B) receptor-mediated responses by forming protein complexes with
      GB(2)R subunit of GABA(B)R at the plasma membranes.

PMID- 17013812
TI  - AF6/s-afadin is a dual residency protein and localizes to a novel subnuclear
      compartment.
AB  - The AF6/afadin protein is a component of cell membranes at specialized sites of
      cell-cell contact. Two main splice variants exist, known as l- and s-afadin,
      respectively. L-afadin is widely expressed in cells of epithelial origin, whilst
      s-afadin expression is restricted to the brain. Here we demonstrate that the
      short form of AF6/s-afadin is a dual residency protein able to localize to the
      plasma membrane or nucleus whilst the long form of AF6, l-afadin is unable to
      localize to the nucleus. AF6/s-afadin clusters in a distinctive speckled pattern
      in the nucleus, but is unable to do so when cell cycle progression is inhibited
      at the G(1)/S or G(2)/M checkpoints. The formation of AF6/s-afadin nuclear bodies
      is also sensitive to the transcriptional activity of the cell with inhibition of
      RNA polymerase activity abolishing AF6/s-afadin nuclear clustering. AF6/s-afadin
      nuclear bodies localize to a novel subnuclear compartment, failing to colocalize
      with other known nuclear bodies. Formation of the AF6/s-afadin nuclear foci can
      be regulated by specific growth factor receptor mediated signaling events and by
      cytoplasmic tyrosine kinases, but does not correlate with tyrosine
      phosphorylation of AF6/s-afadin. AF6/s-afadin is a candidate for mediating
      control of cellular growth processes by regulated translocation to the nucleus.

PMID- 17013813
TI  - Absence of FTL3 mutations in patients with JAK2V617F mutation negative essential
      thrombocythemia.
AB  - A common point mutation in the JAK2 tyrosine kinase leads to constitutive
      hematopoietic growth factor receptor signaling and was recently described in many
      patients with myeloproliferative disorders (MPDs). However, this JAK2 mutation is
      present in only a subset (35-50%) of patients with essential thrombocythemia
      (ET). Thus, the proliferative signals responsible for MPDs in the absence of JAK2
      mutations remain largely unknown. Despite intriguing pre-clinical data, where
      transgenic mice overexpressing FLT3-ITD developed a MPD resembling ET, none of
      the patient samples from ET patients who were JAK2(V617F)-negative demonstrated
      the presence of activating mutations in the FLT3 receptor.

PMID- 17013814
TI  - Glycosyl-phosphatidyl-inositol-defective granulocytes from paroxysmal nocturnal
      haemoglobinuria patients show increased bacterial ingestion but reduced
      respiratory burst induction.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the emergence of a
      GPI-defective clonal hematopoiesis. Its clinical features are hemolytic anemia,
      cytopenia, and thrombosis. Circulating monocytes and granulocytes are largely GPI
      defective in PNH patients. This study aims to investigate the granulocyte
      functional properties in PNH. We analyzed bacterial-dependent intracellular
      ingestion and the consequent activation of oxidative burst in GPI-defective
      granulocytes from four neutropenic PNH patients. Our data show a significant
      increase in the ability of GPI-defective granulocytes to ingest opsonized
      bacteria. In addition, an impaired respiratory burst effectiveness in response to
      two independent bacterial stimuli, the N-formyl-MetLeuPhe (fMLP) synthetic
      bacterial peptide and E. coli, was revealed. The occurrence of neutropenia and
      the severe impairment of oxidative burst, occurring in chronic granulomatosis
      disease, were unable to significantly affect phagocytosis. Thus, additional
      mechanisms, able to differentially affect ingestion ability and respiratory burst
      effectiveness, have to be hypothesized. The reduced burst effectiveness of GPI
      defective granulocytes was maintained after treatment with phorbol 12-myristate
      13-acetate, a pharmacological stimulus able to extensively recruit and to trigger
      intracellular protein kinase C (PKC). Moreover, blocking of PKC has been observed
      to severely affect granulocyte respiratory burst with a mild effect on the
      phagocytosis. These data suggest a role for a modulation of intracellular PKC in
      the pathogenesis of the impaired granulocyte oxidative burst.

PMID- 17013815
TI  - Bone marrow aplasia--a rare complication of imatinib therapy in CML patients.
AB  - Imatinib mesylate therapy in CML patients is a generally well tolerated without
      any significant hematological adverse drug effects. However, complications like
      anemia and cytopenias have been described in literature. A very few case reports
      of bone marrow aplasia following imatinib therapy have been reported so far. We
      here report five patients of CML who developed bone marrow aplasia following
      imatinib therapy.

PMID- 17013816
TI  - Glanzmann's thrombasthenia in two pregnant females.

PMID- 17013817
TI  - Regular virologic surveillance showed very frequent cytomegalovirus reactivation
      in patients treated with alemtuzumab.
AB  - Ten patients with refractory lymphomas or autoimmune cytopenias were treated with
      alemtuzumab, and monitored prospectively for cytomegalovirus (CMV) reactivation
      by antigenemia and polymerase chain reaction. All patients showed virologic CMV
      reactivation. Two patients developed pneumonitis and hepatitis respectively,
      necessitating alemtuzumab withdrawal. Eight patients were asymptomatic, and with
      pre-emptive anti-CMV treatment, alemtuzumab therapy was uninterrupted. All
      patients ultimately achieved virologic remission. The frequent CMV reactivation
      was due to a high background seropositivity rate for CMV, severely
      immunocompromized patients, a sensitive detection method, and the diligence of
      surveillance. Frequent monitoring for and early treatment of CMV reactivation is
      necessary during alemtuzumab therapy.

PMID- 17013818
TI  - Flavonoids from Chinese Viscum coloratum: antiarrhythmic efficacy and ionic
      mechanisms.
AB  - Viscum coloratum flavonoids (VCF) have been demonstrated to produce a variety of
      biological actions. An accumulating line of evidence supported the view that VCF
      may exert protective effects on the cardiovascular system. The aim of the study
      was to assess the antiarrhythmic activity as well as the electrophysiological
      properties of VCF. The antiarrhythmic effects of VCF were observed in a rat model
      of arrhythmia induced by aconitine. VCF significantly and dose-dependently
      increased the dosage of aconitine required to induce the arrhythmia indexes.
      Electrophysiological experiment revealed that VCF shortened APD through
      inhibition of ICa-L.

PMID- 17013819
TI  - Electrostatics dominate quadruplex stability.
AB  - Stabilization of nucleic acid structures results from a balance of multiple
      interactions, including electrostatics, base stacking, hydrophobic interactions,
      hydrogen bonding, van der Waals forces, etc. Nucleic acid quadruplexes are
      unusual structures in that their formation is driven by specific binding of metal
      ions. This unique mode of metal binding, which is tightly coupled to
      oligonucleotide folding, can engender correspondingly unique solution behavior.
      In particular, we show that addition of many cosolvents, such as primary
      aliphatic alcohols, increases the thermal stability of quadruplexes, as
      determined by melting temperature, Tm, in direct contrast to the response of
      duplexes to the same admixture of solvents. Thermal stability is observed to
      increase as the dielectric constant of the composite solvent decreases. This
      behavior suggests a dominant role for electrostatics in quadruplex formation and
      stability. Additional studies done with other cosolvents and solutes suggest
      that, in some cases, other forces may come into play, including the possibility
      of direct interaction with the quadruplex structure. Nonetheless, many cosolvents
      and small molecules, such as ethanol, dimethylformamide, and betaine, stabilize
      the quadruplex conformation in sharp distinction to their destabilization of DNA
      duplexes.

PMID- 17013820
TI  - Liver lift: A simple suture technique for liver retraction during laparoscopic
      gastric surgery.

PMID- 17013821
TI  - Comment on the use of self-reporting instruments to assess patients with
      rheumatoid arthritis: the longitudinal association between the DAS28 and the VAS
      general health.
AB  - OBJECTIVE: Recently, the use of patient self-reporting instruments instead of
      clinical, objective measurements to assess rheumatoid arthritis (RA) patients was
      proposed. This assumes a constant association between disease activity and the
      self-reporting instruments. The objective was to explore the association (in
      time) between disease activity and patient perception of general health, disease
      activity, pain, and functional disability in patients with RA. METHODS: Data of
      624 newly diagnosed RA patients who completed 3 years of followup were analyzed.
      Cross-sectional linear regression models and longitudinal regression models were
      estimated, with a visual analog scale (VAS) measuring general health (VAS-GH; 0 =
      best, 100 = worst) as a dependent variable and the Disease Activity Score (DAS28)
      without the VAS-GH as an independent variable. Other dependent variables were VAS
      disease activity, pain, and the Health Assessment Questionnaire. RESULTS: The
      DAS28 and VAS-GH were significantly associated in RA patients (P < 0.001).
      However, the explained variance was low (6.7%). From diagnosis to 3 years after
      the diagnosis, the intercept decreased given the same regression coefficient. The
      longitudinal regression model showed that the VAS-GH improved during disease
      course independent of a change in DAS28. Analyses on the other outcome parameters
      showed similar results. CONCLUSION: Patients' perception of health can be
      different with equal disease activity, depending on the moment in the disease
      course. Furthermore, our results indicate that self-reported measures on
      functionality, disease activity, and general health cannot substitute for
      objective measures of disease activity in RA in longitudinal studies;
      subsequently, both need to be measured.

PMID- 17013822
TI  - Assessing utility values in rheumatoid arthritis: a comparison between time trade
      off and the EuroQol.
AB  - OBJECTIVE: To compare the utility values and quality-adjusted life years (QALYs)
      obtained by the Time Trade-Off instrument (TTO) and the EuroQol-5D (EQ-5D) in
      patients with rheumatoid arthritis (RA); to analyze the association between
      utility values and Disease Activity Score 28 (DAS28) and Health Assessment
      Questionnaire (HAQ). METHODS: We conducted a longitudinal, prospective, 1-year
      study of RA patients selected randomly from 10 rheumatology clinics. TTO and EQ
      5D were administered at 4 scheduled visits. RESULTS: The study sample comprised
      300 RA patients (82% women, mean age 59 years, mean disease duration 10.3 years).
      A total of 260 patients completed both the TTO and the EQ-5D at baseline, and the
      mean +/- SD TTO scores were significantly higher than the EQ-5D scores (0.81 +/-
      0.22 versus 0.53 +/- 0.35, P < 0.0001). The intraclass correlation coefficient
      (ICC) for the utility methods was 0.19. Data about changes in both TTO and EQ-5D
      scores during the study year were available in 163 patients. These changes tended
      to be larger in the TTO scores than the EQ-5D scores (mean +/- SD 0.05 +/- 0.25
      versus -0.005 +/- 0.35, P = 0.054). The ICC for the mean changes in the utility
      scores was 0.24. Patients obtained a mean +/- SD of 0.04 +/- 0.20 QALYs based on
      TTO scores and 0.004 +/- 0.27 based on EQ-5D scores (P = 0.12). At baseline, the
      EQ-5D scores were highly correlated with the HAQ (r = -0.74) and moderately
      correlated with the DAS28 (r = -0.47), whereas the TTO correlated poorly with
      both the HAQ and DAS28. Correlation between the mean change in the EQ-5D and in
      the HAQ was moderate (r = -0.55). CONCLUSION: TTO and EQ-5D do not yield the same
      utility values. The results suggest that the EQ-5D is more representative of RA
      status than the TTO, a valuable conclusion when addressing economic evaluations
      in RA.

PMID- 17013823
TI  - Impact of multiple joint problems on daily living tasks in people in the
      community over age fifty-five.
AB  - OBJECTIVE: To establish the prevalence of multiple joint problems and their
      impact on everyday tasks. METHODS: A random sample of the UK population was
      assessed using a postal questionnaire. Data on overall joint pain, swelling and
      stiffness, and activities of daily living were obtained from 16,222 individuals
      >55 years of age (86% response rate). Prevalence estimates of joint problems were
      established and the impact of multiple joint pathologies on common physical tasks
      was determined. RESULTS: Single joint involvement was unusual (median joint
      involvement 4). Although the knee was the most frequently involved joint (220.30
      per 1,000), isolated knee pathology accounted for only 1 in 11 patients with knee
      pain. Although single joint disorders increased the risk of experiencing
      functional difficulty, this risk was substantially increased with multiple joint
      problems: individuals with knee and feet problems were 14 times more likely to
      experience difficulty standing and walking than those without knee problems (odds
      ratio [OR] 14.50); knee and hip problems increased the risk >12 times (OR 12.43)
      whereas knee, back, feet, and hip involvement increased the risk 60 times (OR
      62.41). CONCLUSION: Multiple-site joint problems are much more common than single
      joint problems. Although individual joint problems have a considerable impact on
      a person's functional ability, this risk is substantially increased when other
      joints are involved. With the increasing burden associated with the aging
      population, it is essential that the management of joint pain be considered in
      light of the impact of multiple, rather than single, joint problems.

PMID- 17013824
TI  - Epidemiologic surveillance of upper-extremity musculoskeletal disorders in the
      working population.
AB  - OBJECTIVE: Since 2002, an epidemiologic surveillance system of work-related,
      upper-limb musculoskeletal disorders (MSDs) has been implemented in France's Pays
      de la Loire region to assess the prevalence of MSDs and their risk factors in the
      working population. METHODS: The surveillance was based on a network of
      occupational physicians (OPs) and used the recommendations of a group of European
      experts (criteria document consensus). In 2002-2003, 80 of 400 OPs volunteered to
      participate. All underwent a training program to standardize the physical
      examination. Health status was assessed by self-administered questionnaire and
      physical examination. Occupational risk factors were assessed by self
      administered questionnaire. Exposure scores were computed for each anatomic zone
      by summing the risk factors taken into account by the criteria document. RESULTS:
      More than 50% of the 2,685 men and women randomly included in 2002-2003
      experienced nonspecific musculoskeletal symptoms during the preceeding 12 months
      and approximately 30% experienced them in the preceeding week. The prevalence of
      clinically diagnosed MSDs was high: approximately 13% of workers experienced at
      least 1 of the MSDs. The most frequent disorder was rotator cuff syndrome
      followed by carpal tunnel syndrome and lateral epicondylitis. The prevalence of
      MSDs increased with age and varied widely across economic sectors and
      occupations. More than half of the workers were exposed to at least 2 risk
      factors of MSDs. Exposure varied according to industrial activity and occupation.
      According to the criteria document, a high percentage of MSD cases could be
      classified as probably work related (95% in men and 89% in women age <50, and 87%
      in men and 69% in women age >50). CONCLUSION: Nonspecific upper-limb symptoms and
      specific upper-limb MSDs are common in the working population. These results show
      the need to implement prevention programs in most sectors to reduce the
      prevalence of MSDs.

PMID- 17013825
TI  - A comparison of slurry sampling electrothermal vaporization and slurry
      nebulization inductively coupled plasma mass spectrometry for the direct
      determination of trace impurities in titanium dioxide powder.
AB  - A comparison of slurry sampling (SS)-ETV-ICP-MS and slurry nebulization (SN)-ICP
      MS for direct determination of trace impurities in titanium dioxide powder is
      made. The particle size effect, matrix effect and analytical characteristics of
      SSETV-ICP-MS and SN-ICP-MS are compared. The results have shown that SSETV-ICP-MS
      has a lower particle size effect and matrix effect compared to SN-ICP-MS. The
      analytical performance of the two methods reveals that SSETV-ICP-MS and SN-ICP-MS
      have similar relative detection limits (in the nanogram per liter level);
      however, the former has a lower absolute detection limit than the latter.
      Although the precision for SSETV-ICP-MS is a little worse than that for SN-ICP
      MS, it is still acceptable for real sample analysis. The two methods were
      successfully applied for the determination of trace impurities in titanium
      dioxide powder samples with particle sizes of less than 50 nm, but only SSETV-ICP
      MS could be applied for the determination of trace impurities in titanium dioxide
      powder samples with a particle size of 1 microm.

PMID- 17013826
TI  - Characterization of linear and cyclic polylactic acids and their solvolysis
      products by electrospray ionization mass spectrometry.
AB  - Linear and cyclic polylactic acids (PLAs) were characterized using electrospray
      ionization mass spectrometry (ESI-MS) as part of our ongoing investigation of the
      hydrolysis mechanism of biodegradable polymers. The condensation oligomers of
      linear polylactic acid (LPLA) were synthesized by thermal dehydration of L-lactic
      acid. The trimer and tetramer base polymers of cyclic polylactic acid (CPLA) were
      obtained by cyclization reactions of lactic acid trimers and tetramers,
      respectively. In the ESI-MS/MS measurement, LPLA yielded three types of product
      ion series, while CPLA yielded only one type, from which the repeated units of
      CPLA were removed. The MS/MS spectrum of the NH4+ adduct ion for both cyclic and
      linear PLA showed loss of one ammonia molecule. The postsource decay (PSD)
      spectrum of CPLA by matrix-assisted laser desorption ionization (MALDI) mass
      spectrometry was similar to the ESI-MS/MS spectrum, while that of LPLA was
      different. In addition, the degradation of cyclic and linear PLAs by solvolysis
      was investigated. Solvolysis with anhydrous MeOH was quite feasible, but did not
      readily occur in the presence of even a small amount of water in the MeOH
      solvent.

PMID- 17013827
TI  - Course of functional status and pain in osteoarthritis of the hip or knee: a
      systematic review of the literature.
AB  - OBJECTIVE: To systematically review studies describing the course of functioning
      in patients with osteoarthritis (OA) of the hip or knee and identifying potential
      prognostic factors. METHODS: A systematic search was performed. Studies involving
      patients with hip or knee OA, >6 months of followup, and outcome measures on
      functional status or pain were included. Methodologic quality was assessed using
      a standardized set of 11 criteria; a qualitative data analysis was performed.
      RESULTS: Approximately 6,500 titles and abstracts were screened and 48
      publications were considered for inclusion. Eighteen studies, 4 of which met the
      high methodologic quality criteria, were included. For hip OA, there was limited
      evidence that functional status and pain do not change during the first 3 years
      of followup. After 3 years, however, a worsening of functional status and pain
      was seen. For knee OA, there was conflicting evidence for the first 3 years and
      limited evidence for worsening of pain and functional status after 3 years.
      Furthermore, limited evidence was established for negative associations between
      future functional status and laxity, proprioceptive inaccuracy, age, body mass
      index, and knee pain intensity. In contrast, greater muscle strength, better
      mental health, better self-efficacy, social support, and more aerobic exercise
      were protective factors in the first 3 years. CONCLUSION: Pain and functional
      status in hip or knee OA seem to deteriorate slowly, with limited evidence for
      worsening after 3 years of followup. In specific subgroups, prognosis in the
      first 3 years of followup was either worse or better, as both risk factors and
      protective factors were identified. Prognostic factors included biomechanical
      factors, psychological factors, clinical factors, and treatment modalities. To
      strengthen the evidence, further high-quality longitudinal research on hip or
      knee OA functioning is needed.

PMID- 17013828
TI  - Protocols for optimizing MS/MS parameters with an ion-trap GC-MS instrument.
AB  - The product ion spectrum allows us to achieve very selective detection of
      pesticides and to eliminate the ambiguities caused by more conventional
      analytical approaches. Owing to the enhanced capabilities of GC/MS/MS for
      multiresidue pesticides, the development of a GC/MS/MS pesticides library will be
      useful. The aim of this study was to develop a sensitive and specific analytical
      method for the identification and quantification of compounds without the need of
      a time-consuming procedure. Two methods were studied in order to optimize the
      nonresonant conditions of dissociation of five pesticides (deltamethrin,
      metalaxyl, myclobutanil, procymidone, pirimicarb). The first permits a systematic
      investigation of the influence of the qz trapping parameter on sensitivity in
      precursor ion detection and on the efficiency of collision-induced dissociation
      (CID). The second is more suited for analytical laboratories and less time
      consuming and allows us to reach similar results: the experiments were conducted
      step by step at a constant stability parameter.

PMID- 17013829
TI  - Interaction between alpha and upsilon-crystallin, common to the eye of the
      Australian platypus, by radical probe mass spectrometry.
AB  - The interaction between alpha-crystallin and upsilon-crystallin, a class recently
      discovered in the eye of the Australian platypus, has been shown by native shift
      gel assay and examined by radical probe mass spectrometry in the context of the
      ability of alpha-crystallin to protect upsilon-crystallin from oxidation and
      oxidative damage through radical-based oxidative stress mechanisms. Residues 22
      41, 132-148, 212-227 and 245-264 of upsilon-crystallin display the greatest
      protection when interacted with alpha-crystallin at a ratio of 2 : 1 observed for
      the complex, which is commensurate with their levels measured in the eye of the
      platypus. Across each domain, a delay in the onset of oxidative damage is
      observed as the time of exposure to radicals is increased. The results are
      discussed in the context of the structure of the porcine homologue of upsilon
      crystallin.

PMID- 17013830
TI  - Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant
      progression in a murine model of skin carcinogenesis.
AB  - Mice with conditional gene deletions have been extremely valuable in allowing
      investigators to study the genes of interest in a tissue-specific manner. The Cre
      loxP recombination system provides a powerful tool to produce targeted
      rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre)
      transgenic mouse line has been used to generate skin specific gene deletions. We
      found that the K5Cre mice display a unique phenotype when bred to homozygosity.
      The K5Cre(+/+) mice have a wavy hair coat and curly whiskers. Histologically, the
      hair follicles appear disoriented. Over time, the K5Cre(+/+) mice develop patches
      of alopecia. These mice are also runted when compared to wild-type controls.
      Fostering the K5Cre(+/+) pups to wild-type mothers results in normal weight gain,
      suggesting a maternal defect in milk production. When the K5Cre(+/+) mammary
      glands were examined, we not only found a significant decrease in the number of
      mammary branches in the virgin females, but also a greater number of quiescent
      alveoli units in the lactating glands. When the K5Cre(+/+) mice were bred to v-Ha
      ras (Tg . AC) transgenic mice, the resulting Tg . AC(+/-) K5Cre(+/+) offspring
      were utilized in a chemically induced skin carcinogenesis model. The mice were
      treated with 2.5 microg of 12-O-tetradecanoylphorbol-13-acetate (TPA) weekly for
      10 wk. No difference was observed in the time to onset of papilloma formation,
      the number of papillomas and the average papilloma volume between the Tg . AC(+/
      ) K5Cre(+/+) mice and their corresponding controls. Surprisingly, however, the
      K5Cre(+/+) papillomas displayed an accelerated tendency to malignant progression;
      in addition, the frequency of malignant transformation of the papillomas is
      significantly enhanced. Although the K5Cre(+/+) mice resemble waved-1 and -2
      mutants, the molecular basis for the K5Cre(+/+) phenotype is probably different.
      In conclusion, we discovered a unique phenotype associated with the K5Cre(+/+)
      transgenic line.

PMID- 17013831
TI  - High-affinity triplex-forming oligonucleotide target sequences in mammalian
      genomes.
AB  - Site-specific recognition of duplex DNA by triplex-forming oligonucleotides
      (TFOs) provides a promising approach to manipulate mammalian genomes. A
      prerequisite for successful gene targeting using this approach is that the
      targeted gene must contain specific, high-affinity TFO target sequences (TTS). To
      date, TTS have been identified and characterized in only approximately 37 human
      or rodent genes, limiting the application of triplex-directed gene targeting. We
      searched the complete human and mouse genomes using an algorithm designed to
      identify high-affinity TTS. The resulting data set contains 1.9 million potential
      TTS for each species. We found that 97.8% of known human and 95.2% of known mouse
      genes have at least one potential high-affinity TTS in the promoter and/or
      transcribed gene regions. Importantly, 86.5% of known human and 83% of the known
      mouse genes have at least one TTS that is unique to that gene. Thus, it is
      possible to target the majority of human and mouse genes with specific TFOs. We
      found substantially more potential TTS in the promoter sequences than in the
      transcribed gene sequences or intergenic sequences in both genomes. We selected
      12 mouse genes and 2 human genes critical for cell signaling, proliferation,
      and/or carcinogenesis, identified potential TTS in each, and determined TFO
      binding affinities to these sites in vitro. We identified at least one high
      affinity, specific TFO binding site within each of these genes. Using this
      information, many genes involved in mammalian cell proliferation and
      carcinogenesis can now be targeted.

PMID- 17013832
TI  - Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.
AB  - Smoking delays the healing process and increases morbidity associated with many
      common musculoskeletal disorders, including long bone fracture. In the current
      study, a murine model of tibial fracture healing was used to test the hypothesis
      that smoking delays chondrogenesis after fracture. Mice were divided into two
      groups, a nonsmoking control group and a group exposed to cigarette smoke for 1
      month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28
      days after surgery. The outcomes measured were immunohistochemical staining for
      type II collagen protein expression as a marker of cartilage matrix and
      proliferating cell nuclear antigen (PCNA) staining to measure proliferation at
      the site of injury. Toluidine blue staining and histomorphometry were used to
      quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs
      were analyzed for evidence of remodeling after injury. At day 7 after injury,
      mice exposed to cigarette smoke had a smaller fracture callus with less cartilage
      matrix compared to controls. Proliferation was present at high levels in both
      groups at this time point, but proliferating cells had a more immature morphology
      in the smoking group. At day 14, chondrogenesis was more active in smokers
      compared to controls, while a higher percentage of bone was present in the
      control animals. At day 28, X-ray analysis revealed a larger fracture callus
      remaining in the smoking animals. Together, these findings show that the
      chondrogenic phase of tibial fracture healing is delayed by smoking. This study
      represents, to our knowledge, the first analysis of molecular and cellular
      mechanisms of healing in a smoking mouse fracture model.

PMID- 17013833
TI  - Using serum urate levels to determine the period free of gouty symptoms after
      withdrawal of long-term urate-lowering therapy: a prospective study.
AB  - OBJECTIVE: Withdrawal of urate-lowering therapy (ULT) is associated with
      recurrence of acute gouty arthritis and tophi, but no data are available about
      factors associated with recurrence of gouty symptoms. Therefore, life-long
      therapy prescription is usually advised, but the prospect of life-long therapy
      may contribute to very low compliance rates. Our objective was to ascertain the
      outcome of ULT withdrawal after long-term, documented control of serum urate
      levels. METHODS: We conducted a prospective, long-term, followup study of
      patients treated with ULT during a 5-year period. Both diagnosis and recurrence
      of gout were determined based on monosodium urate crystal identification in
      synovial fluid or material aspirated from tophi. RESULTS: Low average serum urate
      levels while receiving ULT and during the followup period after ULT withdrawal
      were statistically associated with the longest period in which patients were free
      of gouty symptoms, suggesting that depletion and formation of the body's urate
      pool is dependent on both time and serum urate levels. Patients whose average
      serum urate levels were <5.05 mg/dl while receiving ULT and <8.75 mg/dl after ULT
      withdrawal had the longest (>4 years) time to recurrence. CONCLUSION: Proper and
      long-term reduction of serum urate level is associated with long-term periods in
      which patients are free of gouty symptoms, probably due to the reduction of the
      urate pool. These results suggest that 5-year intermittent, instead of life-long,
      ULT could be offered to patients with good serum urate control during ULT.

PMID- 17013834
TI  - Combined effects of p73 and MDM2 polymorphisms on the risk of lung cancer.
AB  - p73, a structural and functional homologue of p53, plays an important role in
      modulating cell-cycle control and apoptosis. MDM2 represses the transcriptional
      activity of p73 and thus attenuates its activity. Based on the interaction
      between p73 and MDM2 in cell-cycle control and apoptosis, we investigated the
      association between p73 G4C14-to-A4T14 and MDM2 309T > G polymorphisms, alone and
      in combination, on the risk of lung cancer in a Korean population. The p73 and
      MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy
      control subjects who were frequency-matched for age and gender. The p73 AT/AT and
      MDM2 309 GG genotypes were associated with a nonsignificant increased risk of
      lung cancer (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.83
      2.24; and adjusted OR = 1.29, 95% CI = 0.92-1.80, respectively), compared with
      their wild-type genotypes, respectively. When the p73 and MDM2 polymorphisms were
      combined, the risk of lung cancer increased in a dose-dependent manner as the
      number of variant alleles increased (Ptrend = 0.01). Subjects with three or four
      variant alleles were at a significantly increased risk of lung cancer (adjusted
      OR = 1.74, 95% CI = 1.11-2.74, P = 0.02) compared to subjects with zero variant
      allele. These results suggest an additive effect of the p73 and MDM2 variant
      alleles on an increased risk of lung cancer.

PMID- 17013835
TI  - Lead promotes abasic site accumulation and co-mutagenesis in mammalian cells by
      inhibiting the major abasic endonuclease Ape1.
AB  - Lead is a widespread environmental toxin, found in contaminated water sources,
      household paints, and certain occupational settings. Classified as a probable
      carcinogen by the International Agency for Research on Cancer (IARC), lead
      promotes mutagenesis when combined with alkylating and oxidizing DNA-damaging
      agents. We previously reported that lead inhibits the in vitro repair activity of
      Ape1, the major endonuclease for repairing mutagenic and cytotoxic abasic sites
      in DNA. We investigated here whether lead targets Ape1 in cultured mammalian
      cells. We report a concentration-dependent inhibition of apurinic/apyrimidinic
      (AP) site incision activity of Chinese hamster ovary (CHO) AA8 whole cell
      extracts by lead. In addition, lead exposure results in a concentration-dependent
      accumulation of AP sites in the genomic DNA of AA8 cells. An increase in the
      oxidative base lesion 8-oxoguanine was observed only at high lead levels (500
      microM), suggesting that non-specific oxidation plays little role in the
      production of lead-related AP lesions at physiological metal concentrations--a
      conclusion corroborated by "thiobarbituric acid reactive substances" assays.
      Notably, Ape1 overexpression in AA8 (hApe1-3 cell line) abrogated the lead
      dependent increase in AP site steady-state levels. Moreover, lead functioned
      cooperatively to promote a further increase in abasic sites with agents known to
      generate AP sites in DNA (i.e., methyl methansulfonate (MMS) and hydrogen
      peroxide (H2O2), but not the DNA crosslinking agent mitomycin C. Hypoxanthine
      guanine phosphoribosyltransferase (hprt) mutation analysis revealed that, whereas
      lead alone had no effect on mutation frequencies, mutagenesis increased in MMS
      treated, and to a greater extent lead/MMS treated, AA8 cells. With the hApe1-3
      cell line, the number of mutant colonies in all treatment groups was found to be
      equal to that of the background level, indicating that Ape1 overexpression
      reverses MMS- and lead-associated hprt mutagenesis. Our studies in total indicate
      that Ape1 is a member of an emerging group of DNA surveillance proteins that are
      inhibited by environmental heavy metals, and suggest an underlying mechanism by
      which lead promotes co-carcinogenesis.

PMID- 17013836
TI  - Neoplastic hepatocyte growth associated with cyclin D1 redistribution from the
      cytoplasm to the nucleus in mouse hepatocarcinogenesis.
AB  - Cyclin D1 overexpression is a frequent change in hepatocellular carcinomas
      (HCCs). Our present study demonstrated that cyclin D1 overexpression with
      abundant cyclin E, cdk4, cdk2, and p27Kip1 (p27) occurred in neoplastic
      hepatocytes from the early stage of mouse hepatocarcinogenesis. While cyclin D1
      expression was mainly found in the cytoplasm of the tumor cells, it shifted to
      the nucleus in association with cell proliferation after the animals were
      subjected to a partial hepatectomy (PH), and then returned once more to the
      cytoplasm when the cells became quiescent. Inhibition of PI3 kinase (PI3K) by
      Ly294002 in mouse HCC cells in vitro suppressed the nuclear shift of cyclin D1 as
      well as cell proliferation, while PI3K activation by PTEN suppression failed to
      induce nuclear shift of cyclin D1, suggesting that PI3K activation is essential
      but not sufficient for the cyclin D1 nuclear shift. While MEK-ERK1/2 inhibition
      by PD98059 and mTOR inhibition by rapamycin affected the cyclin D1 nuclear shift
      and cell proliferation to a lesser extent, both these inhibitors reduced cyclin
      D1 levels. Finally, although p27, cdk4 and calmodulin (CaM) were detected in the
      cyclin D1 immunoprecipitates from both quiescent and proliferating HCC cells,
      Hsc70 and SSeCKS were detected only in the immunoprecipitate from quiescent
      cells, and p21Waf1/Cip1 (p21) was detected only in that from proliferating cells,
      suggesting that the cyclin D1 complex is different in quiescent and proliferating
      cells. These observations indicate that the nuclear/cytoplasmic localization of
      cyclin D1 plays an important role in the proliferation/quiescence of neoplastic
      hepatocytes.

PMID- 17013837
TI  - Myositis-specific and myositis-associated antibodies in a series of eighty-eight
      Mediterranean patients with idiopathic inflammatory myopathy.
AB  - OBJECTIVE: To determine the prevalence of myositis-specific autoantibodies (MSAs)
      and myositis-associated autoantibodies (MAAs) and their clinical and
      immunogenetic correlations in Mediterranean patients with idiopathic inflammatory
      myopathies. METHODS: Sera from 88 patients were studied for MSAs and MAAs by RNA
      and protein immunoprecipitation. HLA typing was performed by sequence-specific
      primer- and sequence-specific oligonucleotide-polymerase chain reaction and
      serology. Statistical analyses were performed with Student's t-test and Fisher's
      exact test. Cumulative survival probabilities were estimated by the Kaplan-Meier
      method and Cox regression analysis. RESULTS: Twenty-eight patients (30%) had
      MSAs, most commonly antisynthetase antibodies (23.9%). Six patients (7.5%) had
      anti-Mi-2 antibodies. No anti-signal recognition particles were found. Arthritis,
      mechanic's hands, interstitial lung disease, and sicca syndrome were more
      prevalent in patients with antisynthetase antibodies. Dysphagia and the need for
      more treatment courses were more frequent in patients who were anti-Mi-2
      positive. Forty-three patients (48%) had MAAs, 20 (22%) with anti-Ro 60 and 18
      (20.4%) with anti-Ro 52. Ten patients (11.4%) were positive for anti-PM-Scl, 6
      (6.8%) for anti-RNP, and 1 for anti-Ku antibodies. Patients with PM-Scl, RNP, or
      Ro antibodies were more often classified as having overlap syndrome.
      Immunogenetic studies found a significant association between HLA-DR3 and the
      presence of antisynthetase antibodies (P = 0.049), anti-PM-Scl antibodies (P =
      0.017), and interstitial lung disease (P = 0.03). No statistically significant
      differences in mortality, survival, or clinical course were observed between
      patients positive for MSAs or MAAs and the remaining patients. CONCLUSION: These
      results are consistent with those from other published series, although some
      differences warrant consideration. Autoantibody studies may be useful for
      defining more homogeneous groups of patients with idiopathic inflammatory
      myopathies.

PMID- 17013838
TI  - Transgenic mice for Cre-inducible overexpression of the oncogenes c-MYC and Pim-1
      in multiple tissues.
AB  - The transcription factor c-MYC and the serine-threonine kinase Pim-1 have
      multiple roles in development and cancer, including in lymphomagenesis and
      prostate tumorigenesis. In some cancers, MYC and Pim-1 oncogenes are co-expressed
      and show marked cooperativity. To facilitate the analysis of the pathological
      roles of MYC and Pim-1 in specific cell types and developmental stages, we
      generated mice carrying Cre-inducible MYC/Pim-1 transgenes. The mice carry a
      constitutively expressed lacZ marker and silent MYC/Pim-1 genes. Cre-mediated
      recombination results in deletion of the lacZ marker and concurrent activation of
      the MYC/Pim-1 transgene. In addition, the Pim-1 mice harbor an alkaline
      phosphatase gene as a positive marker for recombination. Mouse lines for each
      gene were established, which show distinct patterns of expression in multiple
      tissues. In vivo recombination was confirmed for all lines by breeding to Cre
      transgenic mice. These mice provide a valuable resource for investigating the
      significance of MYC and Pim-1 overexpression in various tissues.

PMID- 17013839
TI  - Effects of cigarette smoking on early medial collateral ligament healing in a
      mouse model.
AB  - Cigarette smoking delays the healing process and increases morbidity associated
      with many common musculoskeletal disorders such as medial collateral ligament
      (MCL) injury. In the current study, a murine model of MCL healing was used to
      test the hypothesis that smoking impairs extracellular matrix synthesis after
      injury. Mice were divided into two groups, a nonsmoking control group and a group
      exposed to smoke for 2 months prior to surgical MCL injury. Mice were euthanized
      at 3 and 7 days after surgery. Subsequently, propidium iodine staining was used
      to quantify cellular density of injured and sham ligaments. Immunohistochemical
      staining and in situ hybridization to mRNA were used to detect proliferation,
      apoptosis, and type I collagen gene expression at the site of injury. Cell
      density increased significantly from baseline to 7 days after injury in control
      mice. In mice exposed to cigarette smoke, there was a significantly lower
      cellular density compared to controls at this time point (p=0.01). There was no
      difference in proliferation between groups at the site of injury, and the low
      level of proliferation observed was not sufficient to account for the large
      increase in cell density by day 7. No evidence of apoptosis was observed in any
      of the groups at the site of injury. Type I collagen gene expression was higher
      in controls compared to smokers at day 7. Almost all of the cells in the
      substance of the injured MCL at day 7 were spindle-shaped and expressed type I
      collagen, suggesting that increased cell density from day 3 to day 7 represented
      an increase in ligament cells rather than an increased inflammatory response. We
      conclude that the decreased cellular density and type I collagen expression in
      the injured ligament of mice exposed to smoke begin to provide a cellular and
      molecular basis for delayed or deficient early healing in these animals.

PMID- 17013840
TI  - Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: association of
      lymphopenia with clinical manifestations, serologic abnormalities, disease
      activity, and damage accrual.
AB  - OBJECTIVE: To determine if lymphopenia is associated with clinical/immunologic
      manifestations, disease activity, and disease damage in systemic lupus
      erythematosus (SLE). METHODS: The study group comprised 591 patients with SLE
      participating in a multiethnic, longitudinal outcome study. Cumulative
      clinical/immunologic (per American College of Rheumatology criteria) and
      pharmacologic treatment variables were obtained at enrollment (T0) and last visit
      (TL). Lymphopenia (<1,500/mm3) was scored only when clinically attributable to
      SLE and not to medications or other causes. Lymphocyte counts were expressed in 4
      categories per the Systemic Lupus Activity Measure (SLAM): normal (> or
      =1,500/mm3), mild (1,000-1,499/mm3), moderate (500-999/mm3), and marked
      (<500/mm3). Disease activity was assessed with the SLAM and the Physician's
      Global Assessment (PGA). Disease damage was determined with the Systemic Lupus
      International Collaborating Clinics Damage Index (SLICC-DI). The relationship of
      lymphopenia with cumulative clinical/immunologic and pharmacologic treatment
      variables was first examined, then the association between the SLAM, PGA, and
      SLICC-DI scores with different categories of lymphopenia was examined by
      generalized estimating equation (GEE) regression analyses. Ethnicity, age, and
      sex were entered into all regression models. RESULTS: At T0 and TL, lymphopenia
      was found to be positively associated with renal involvement, leukopenia, anti
      double-stranded DNA antibodies, anti-Ro antibodies, and the use of
      glucocorticoids, azathioprine, and methotrexate, but was negatively associated
      with photosensitivity. On GEE analyses, marked lymphopenia at T0 and moderate and
      marked lymphopenia for all visits were independently associated with higher SLAM,
      PGA, and SLICC-DI scores. CONCLUSION: Lymphopenia is associated with several
      clinical/immunologic manifestations in SLE. Moderate and marked lymphopenia are
      associated with higher disease activity and damage accrual.

PMID- 17013841
TI  - Magnetic resonance spectroscopy in the evaluation of central nervous system
      manifestations of systemic lupus erythematosus.

PMID- 17013843
TI  - Looking beyond the ordinary: genital lupus.

PMID- 17013842
TI  - Switching from infliximab to once-weekly administration of 50 mg etanercept in
      resistant or intolerant patients with ankylosing spondylitis: results of a fifty
      four-week study.

PMID- 17013844
TI  - Epstein-Barr virus-associated B cell lymphoproliferative disease in a child with
      neonatal-onset multisystem inflammatory disease.

PMID- 17013845
TI  - Case report and review of cardiac tamponade in mixed connective tissue disease.

PMID- 17013846
TI  - Additional case of minocycline-induced cutaneous polyarteritis nodosa: comment on
      the article by Culver et al.

PMID- 17013849
TI  - Cyclooxygenase 2 controversy: thoughts on the process of discovery, development,
      and assessment of benefit and risk of therapies for chronic immunoinflammatory
      diseases of uncertain autoimmune etiology.

PMID- 17013850
TI  - Examining the consequences of rehabilitation interventions on disease progression
      and functional decline: is function really the only thing that matters?

PMID- 17013851
TI  - Effects of strength training on the incidence and progression of knee
      osteoarthritis.
AB  - OBJECTIVE: Quadriceps weakness is a risk factor for incident knee osteoarthritis
      (OA). We describe a randomized controlled trial of effects of lower-extremity
      strength training on incidence and progression of knee OA. METHODS: A total of
      221 older adults (mean age 69 years) were stratified by sex, presence of
      radiographic knee OA, and severity of knee pain, and were randomized to strength
      training (ST) or range-of-motion (ROM) exercises. Subjects exercised 3 times per
      week (twice at a fitness facility, once at home) for 12 weeks, followed by
      transition to home-based exercise after 12 months. Assessments of isokinetic
      lower-extremity strength and highly standardized knee radiographs were obtained
      at baseline and 30 months. RESULTS: Subjects in both groups lost lower-extremity
      strength over 30 months; however, the rate of loss was slower with ST than with
      ROM. Compared with ROM, ST decreased the mean rate of joint space narrowing (JSN)
      in osteoarthritic knees by 26% (P = not significant). However, the difference
      between ST and ROM groups with respect to frequency of knee OA progression in JSN
      consensus ratings was marginally significant (18% versus 28%; P = 0.094). In
      knees that were radiographically normal at baseline, JSN >0.50 mm was more common
      in ST than in ROM (34% versus 19%; P = 0.038). Incident JSN was unrelated to
      exercise adherence or changes in quadriceps strength or knee pain. CONCLUSION:
      The ST group retained more strength and exhibited less frequent progressive JSN
      over 30 months than the ROM group. The increase in incident JSN >0.50 mm in ST is
      unexplained and requires confirmation.

PMID- 17013852
TI  - Effect of preoperative exercise on measures of functional status in men and women
      undergoing total hip and knee arthroplasty.
AB  - OBJECTIVE: To evaluate the effect of a short preoperative exercise intervention
      on the functional status, pain, and muscle strength of patients before and after
      total joint arthroplasty. METHODS: A total of 108 men and women scheduled for
      total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to
      a 6-week exercise or education (control) intervention immediately prior to
      surgery. We assessed outcomes through questionnaires and performance measures.
      Analyses examined differences between groups over the preoperative and immediate
      postoperative periods and at 8 and 26 weeks postsurgery. RESULTS: Among THA
      patients, the exercise intervention was associated with improvements in
      preoperative Western Ontario and McMaster Universities Osteoarthritis Index
      function score (improvement of 2.2 in exercisers versus decline of 3.9 in
      controls; P = 0.02) and Short Form 36 physical function score (decline of 0.4 in
      exercisers versus decline of 14.3 in controls; P = 0.003). No significant
      differences were seen in TKA patients. Exercise participation increased muscle
      strength preoperatively (18% in THA patients and 20% in TKA patients), whereas
      the control patients had essentially no change in strength (P > 0.05 for exercise
      versus education in both THA and TKA groups). Exercise participation prior to
      total joint arthroplasty substantially reduced the risk of discharge to a
      rehabilitation facility in THA and TKA patients (adjusted odds ratio 0.27, 95%
      confidence interval 0.074-0.998). The intervention had no effects on outcomes 8
      and 26 weeks postoperatively. CONCLUSION: A 6-week presurgical exercise program
      can safely improve preoperative functional status and muscle strength levels in
      persons undergoing THA. Additionally, exercise participation prior to total joint
      arthroplasty dramatically reduces the odds of inpatient rehabilitation.

PMID- 17013853
TI  - Development of sarcoidosis during etanercept therapy.

PMID- 17013854
TI  - Musculoskeletal screening examination (pGALS) for school-age children based on
      the adult GALS screen.
AB  - OBJECTIVE: To develop and validate a musculoskeletal screening examination
      applicable to school-age children based on the adult Gait, Arms, Legs, Spine
      (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children
      attending pediatric rheumatology clinics and was compared with an examination
      conducted, on the same day, by a pediatric rheumatologist who classified children
      as having abnormal or normal joints. Adult GALS was tested for validity compared
      with the pediatric rheumatologist's assessment and deficiencies in adult GALS
      were identified. Experts proposed amendments to adult GALS, achieving consensus
      by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was
      tested (methodology identical to the testing of adult GALS) in an additional
      group of children. RESULTS: Adult GALS was tested in 50 children (median age 11
      years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult
      GALS missed important abnormalities in 18% of children, mostly at the ankle,
      foot, and temporomandibular joints. The pGALS was tested in 65 children (median
      age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%)
      and specificity (98-100%) at all joints, with high acceptability scored by child
      and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3
      minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent
      validity, is quick to perform, and is acceptable to school-age children and
      parents/guardians. We propose that pGALS be incorporated into undergraduate and
      postgraduate medical training to improve pediatric musculoskeletal clinical
      skills and facilitate diagnosis and referral to specialists.

PMID- 17013855
TI  - Use of the Sharp and Larsen scoring methods in the assessment of radiographic
      progression in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the applicability of the Sharp and Larsen scoring
      methods for radiographic damage in juvenile idiopathic arthritis (JIA). METHODS:
      Wrist/hand radiographs of 25 patients with polyarthritis obtained at first
      observation and then yearly for 4-5 years were assessed independently by 2
      pediatric rheumatologists according to the Sharp and Larsen methods. To
      facilitate score assignment, each patient radiograph was compared with a bone age
      related standard. A third pediatric rheumatologist measured the Poznanski score,
      and a pediatric radiologist provided a semiquantitative assessment of
      radiographic damage severity. RESULTS: Interobserver and intraobserver agreement
      on longitudinal scores were good for both Sharp and Larsen methods, with
      intraclass correlation coefficient >0.9. Agreement on change assessment was good
      for the Sharp method and moderate for the Larsen method. Both methods yielded a
      steady increase in scores during the study, with score change being more marked
      in the first year. Sharp and Larsen scores were highly correlated (r(s) = 0.96).
      Correlations of both scores with the Poznanski score were moderate to high (r(s)
      from -0.62 to -0.72). Radiologist score was correlated at borderline-high level
      with both Sharp (r(s) = 0.70) and Larsen (r(s) = 0.71) scores. Sharp and Larsen
      score change from baseline to final visit was moderately to highly correlated
      with the number of joints with active arthritis and restricted motion and the
      Childhood Health Assessment Questionnaire score at final visit. CONCLUSION: Our
      results demonstrate that the Sharp and Larsen scoring systems are potentially
      reliable and valid for assessment of radiographic progression in patients with
      polyarticular JIA.

PMID- 17013856
TI  - Fabrication and in vitro characterization of porous biodegradable composites
      based on phosphate glasses and oligolactide-containing polymer networks.
AB  - Degradable porous composite materials for use as temporary bone replacement or
      tissue engineering scaffolds were produced using a methacrylate-modified
      oligolactide polymer network and phosphate invert glasses in the system P2O5-CaO
      MgO-Na2O-(TiO2). Porous glasses with an open interconnective porosity were
      produced by a salt sintering process. Compressive strengths were significantly
      enhanced by polymer coating of the inner surface of the porous glasses or by
      fabrication of glass powder-reinforced porous polymer specimens. In vitro
      degradation in simulated body fluid showed a degradation pattern of the
      composites which could be modulated by the composition and resulting solubility
      of the incorporated glass phase. Cytocompatibility of the composites was
      investigated in a FDA/EtBr viability assay using an MC3T3-E1 osteoblast-like cell
      line and showed good biocompatibility of the materials in vitro.

PMID- 17013857
TI  - BMP-7 and CBFA1 in allograft bone in vivo bone formation and the influence of
      gamma-irradiation.
AB  - An initial study showed that morselized human bone grafts were osteoconductive
      and osteoinductive when implanted in nude rat tibial window defects, and 25 kGy
      of gamma-irradiation significantly reduced those properties. The mechanism of the
      osteoinductivity and the influence of gamma-irradiation required further
      investigation. In this study we assessed the paraffin sections of seven
      morselized human bone grafts implanted into rat tibial defects for 3 weeks after
      being treated with 0, 15, or 25 kGy gamma-radiation respectively. Osteoclast-like
      cell counting and protein expressions of bone morphogenetic protein-7 (BMP-7),
      core binding factor alpha1 (CBFA1), and proliferating cell nuclear antigen (PCNA)
      were investigated and the positive signals were quantitatively analyzed. More new
      bone formation was observed in the 0 and 15 kGy groups compared with 25 kGy
      groups. The newly formed bones were found mainly from the intact cortex into the
      defects bridged by the implanted grafts. A dense staining of BMP-7 and CBFA1 was
      noted in the osteoblast-like cells in those areas. The BMP-7 and CBFA1 staining
      was also seen in the cells surrounding the implanted grafts in the centre areas
      of the defects in distance from the intact cortex. Quantitative analysis of
      immunohistochemical staining of the centre areas of the defects showed that gamma
      irradiation (15 and 25 kGy) significantly reduced the expression of CBFA1 and BMP
      7. In conclusion, morselized human bone grafts may contain some factors, which
      induced osteoblast lineage differentiation and bone formation and gamma
      irradiation damages those bone inducing factors.

PMID- 17013858
TI  - Hypoxia leads to necrotic hepatocyte death.
AB  - Hepatocyte transplantation is being investigated as a therapy for liver disease;
      however, its success has been limited by rapid death of the cells following
      transplantation. This study was dedicated to elucidating the mode of death
      responsible for loss of transplanted hepatocytes in order to guide future
      strategies for promoting their survival. Using a tissue engineering model, it was
      found that the environment within polymer scaffolds containing transplanted cells
      was hypoxic after 5 days in vivo, with (90 +/- 3)% of hepatocytes existing at
      pO(2) < 10 mmHg. The primary mode of hepatocyte death in response to hypoxic
      conditions of 0 or 2 vol % oxygen was then determined in vitro. Several assays
      for features of apoptosis and necrosis demonstrated that hepatocytes cultured in
      an anoxic environment died via necrosis, while culture at 2% oxygen inhibited
      proliferation. These results suggest it will not be possible to prevent
      hepatocyte death by interfering with the apoptotic process, and hypoxic
      conditions in the transplants must instead be addressed. The finding that the
      environment within cell transplantation scaffolds is hypoxic is likely applicable
      to many cell-based therapies, and a similar analysis of the primary mode of death
      for other cell types in response to hypoxia may be valuable in guiding future
      strategies for their transplantation.

PMID- 17013859
TI  - Fabrication and characterization of hydrophilized porous PLGA nerve guide
      conduits by a modified immersion precipitation method.
AB  - Nerve guide conduits (NGCs) with selective permeability and hydrophilicity were
      fabricated using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a
      modified immersion precipitation method developed by our laboratory. The
      hydrophilized porous PLGA tubes as NGCs were fabricated by immersing a water
      saturated rod-shape alginate hydrogel into PLGA/Pluronic F127 mixture solution
      (in tetraglycol). The PLGA/Pluronic F127 mixture was precipitated outside the
      alginate hydrogel rod by the diffusion of water from the hydrogel rod into
      PLGA/Pluronic F127 mixture solution. The inner diameter and wall thickness of
      tubes could be easily controlled by adjusting the diameter of alginate hydrogel
      rod and immersion time, respectively. It was observed that the tube wall has an
      asymmetric column-shape porous structure. The inner surface of the tube had nano
      size pores ( approximately 50 nm), which can effectively prevent from fibrous
      tissue infiltration but permeate nutrients and retain neurotrophic factors, while
      the outer surface had micro-size pores ( approximately 50 microm), which can
      allow vascular ingrowth for effective supply of nutrients and oxygen into the
      tube. From the investigations of mechanical property, water absorbabiliy, and
      model nutrient permeability of the tubes, the hydrophilized PLGA/F127 (3 wt %)
      tube seems to be a good candidate as a NGC for the effective permeation of
      nutrients as well as the good mechanical strength to maintain a stable support
      structure for the nerve regeneration.

PMID- 17013860
TI  - In vitro degradation of biodegradable blending materials based on poly(p
      dioxanone) and poly(vinyl alcohol)-graft-poly(p-dioxanone) with high molecular
      weights.
AB  - Amphiphilic biodegradable graft copolymer, poly(vinyl alcohol)-graft-poly(p
      dioxanone) (PVA-g-PPDO), was used to prepare a new biodegradable material by
      blending with poly(p-dioxanone) (PPDO). The in vitro degradation properties of
      the copolymer and blends with different contents of PVA-g-PPDO were studied in
      phosphate buffer at 37 degrees C. The degradation processes of the PVA-g-PPDO and
      its blends with the PPDO were monitored by weight loss, viscosimetry, water
      uptake, differential scanning calorimetry (DSC), and scanning electron
      microscopy. The results of inherent viscosity and weight loss reveal that the PVA
      g-PPDO has a different in vitro degradation behavior from that of PPDO, and the
      introducing of copolymer into the blending system may enhance the degradability
      of PPDO when the contents of copolymer is higher than 5%. The change of the
      degree of crystallization (Dc) of copolymer and blends derived from the DSC also
      shows that the copolymer and blends have faster degradation rates than the neat
      PPDO during the testing period. A degradation mechanism of the blends was
      postulated based on the results of the weight retention, inherent viscosity
      measurement, and DSC.

PMID- 17013861
TI  - Proliferation of anterior cruciate ligament cells in vitro by photo-immobilized
      epidermal growth factor.
AB  - The purpose of this study was to explore the early treatment potential of
      anterior cruciate ligament (ACL) injuries using artificial juxtacrine stimulation
      by photo-immobilization of a growth factor. A photo-reactive epidermal growth
      factor complex (EGF-Az) was synthesized by conjugating EGF with N-(4
      azidobenzoyloxy) succinimide followed by immobilization onto polystyrene culture
      plates using UV irradiation. ACL cells from human tissues (1 x 10(5)cells, 100
      microl/well) were cultured as follows: control, no EGF; 50 microl native EGF; 50
      microl EGF-Az immobilized; and 100 microl EGF-Az immobilized. The ACL cells were
      cultured long-term and evaluated for possible differences in their responses to
      EGF. An in vitro wound closure assay was developed to enable examination of
      cellular proliferation and migration. ACL cell proliferation was most evident in
      the photo-immobilized EGF culture group and was seen to increase in proportion to
      the amount of added EGF. In the in vitro wound closure assay, the lesioned area
      at 72 h after culture initiation was indistinguishable in the photo-immobilized
      cultures, but remained clearly visible in the controls. We conclude that photo
      immobilized EGF induced rapid proliferation of ACL fibroblast cells by artificial
      juxtacrine stimulation and speculate that similar EGF immobilization onto
      bioabsorbable material (e.g., polyglycolic acid or polylactic acid) might
      contribute to a new therapy for the treatment of ACL injuries.

PMID- 17013862
TI  - Activation of demineralized bone matrix by genetically engineered human bone
      morphogenetic protein-2 with a collagen binding domain derived from von
      Willebrand factor propolypeptide.
AB  - There is a large demand for new bone regeneration to restore the function during
      bone injuries. Bone filling materials are important in bone tissue restoration.
      In this study, the demineralized bone matrix (DBM) was activated with the
      engineering human bone morphogenetic protein-2 (BMP-2). To enhance the binding of
      BMP-2 to the DBM scaffolds, a collagen-binding peptide was fused to the N
      terminal of BMP-2. The in vitro results showed that the engineered collagen
      targeted BMP-2 (rhBMP2-v) bound to DBM scaffolds specifically and the rhBMP2-v
      had increased alkaline phosphatase activity in C2C12 cells. In vivo, the DBM
      scaffolds impregnated with rhBMP2-v showed greater effect on ectopic bone
      formation. Our data suggested that the collagen-based BMP-2 targeting bone repair
      system had greater bone inducing ability than DBM loaded with regular BMP-2.

PMID- 17013863
TI  - A novel synthetic tissue-adhesive hydrogel using a crosslinkable polymeric
      micelle.
AB  - We prepared a novel tissue-adhesive hydrogel by using a polymeric micelle
      consisting of an aldehyde-terminated poly(ethylene glycol)-poly(D,L-lactide) (PEG
      PLA) block polymer. A Schiff base is chemically formed between the amino groups
      in a polyallylamine and the aldehyde groups on the surface of polymeric micelles.
      The hydrogel was formed in approximately 2 s when the polymeric micelle solution
      and polyallylamine solution are mixed in vitro. The hydrogel was rapidly formed
      in vivo, and it adhered to a tissue surface. Our novel tissue-adhesive hydrogel
      creates no risk of infectious contaminations, because it consists of only
      synthetic materials. Further, PEG and PLA are known to be biocompatible and
      noncytotoxic. The results obtained in the present study show that a hydrogel
      prepared by the formation of a Schiff base between aldehyde and amine groups will
      potentially address the need for novel tissue-adhesive materials.

PMID- 17013864
TI  - Conjugation of extracellular matrix proteins to basal lamina analogs enhances
      keratinocyte attachment.
AB  - The dermal-epidermal junction of skin contains extracellular matrix proteins that
      are involved in initiating and controlling keratinocyte signaling events such as
      attachment, proliferation, and terminal differentiation. To characterize the
      relationship between extracellular matrix proteins and keratinocyte attachment, a
      biomimetic design approach was used to precisely tailor the surface of basal
      lamina analogs with biochemistries that emulate the native biochemical
      composition found at the dermal-epidermal junction. A high-throughput screening
      device was developed by our laboratory that allows for the simultaneous
      investigation of the conjugation of individual extracellular matrix proteins
      (e.g. collagen type I, collagen type IV, laminin, or fibronectin) as well as
      their effect on keratinocyte attachment, on the surface of an implantable
      collagen membrane. Fluorescence microscopy coupled with quantitative digital
      image analyses indicated that the extracellular matrix proteins adsorbed to the
      collagen-GAG membranes in a dose-dependent manner. To determine the relationship
      between extracellular matrix protein signaling cues and keratinocyte attachment,
      cells were seeded on protein-conjugated collagen-GAG membranes and a tetrazolium
      based colorimetric assay was used to quantify viable keratinocyte attachment. Our
      results indicate that keratinocyte attachment was significantly enhanced on the
      surfaces of collagen membranes that were conjugated with fibronectin and type IV
      collagen. These findings define a set of design parameters that will enhance
      keratinocyte binding efficiency on the surface of collagen membranes and
      ultimately improve the rate of epithelialization for dermal equivalents.

PMID- 17013865
TI  - Kitagawa-Takahashi diagrams define the limiting conditions for cyclic fatigue
      failure in human dentin.
AB  - As cyclic fatigue is considered to be a major cause of clinical tooth fractures,
      achieving a comprehensive understanding of the fatigue behavior of dentin is of
      importance. In this note, the fatigue behavior of human dentin is examined in the
      context of the Kitagawa-Takahashi diagram to define the limiting conditions for
      fatigue failure. Specifically, this approach incorporates two limiting threshold
      criteria for fatigue: (i) a threshold stress for fatigue failure, specifically
      the smooth-bar (unnotched) fatigue endurance strength, at small crack sizes and
      (ii) a threshold stress-intensity range for fatigue-crack growth at larger crack
      sizes. The approach provides a "bridge" between the traditional fatigue life and
      fracture mechanics based damage-tolerant approaches to fatigue-life estimation,
      and as such defines a "failure envelope" of applied stresses and flaw sizes where
      fatigue failure is likely in dentin This approach may also be applied to fatigue
      failure in human cortical bone (i.e. clinical "stress fractures"), which exhibits
      similar fatigue behavior characteristics, and in principle may aid clinicians in
      making quantitative evaluations of the risk of fractures in mineralized tissues.

PMID- 17013866
TI  - Titanate biomaterials with enhanced antiinflammatory properties.
AB  - While titanium implants are generally recognized as having excellent
      biocompatibility, the mechanistic basis for this has yet to be established. We
      previously demonstrated that TiO2, found on surfaces of titanium, has antioxidant
      properties that degrade the reactive oxygen species (ROS) which mediate the
      inflammatory response. We hypothesized that the antioxidant mechanism was similar
      to that known to mediate photocatalysis by titanium oxides. Specifically, we
      investigated whether the electronic or valence state of the surface titanium
      atoms mediates the catalytic degradation of ROS. Surface Ti(IV) atoms in TiO2 and
      SrTiO3 single crystal substrates were converted into Ti(III) while maintaining
      the bulk crystalline structure by vacuum annealing or Niobium doping. The
      degradation of both chemically-induced and neutrophil-derived ROS were
      significantly increased by changing the valence state of surface titanium. These
      results suggest that titanium-mediated degradation of ROS is through a catalytic
      mechanism. Furthermore, we describe a series of novel biomaterials that have
      antioxidant properties superior to those of titanium.

PMID- 17013867
TI  - Three-dimensional collagen fiber remodeling by mesenchymal stem cells requires
      the integrin-matrix interaction.
AB  - Tissue engineering aiming to repair or regenerate damaged tissues necessitates
      fabricating three-dimensional biomaterial scaffolds with controlled porosity for
      delivering cells. To facilitate cell distribution, a strategy using stem cell
      based fabrication of biomaterials was tested in type II collagen fibers. Human
      mesenchymal stem cells when delivered in type II collagen assembled and
      reorganized these matrices and differentiated into spherical chondrocytes with
      the synthesis of cartilage proteins. The cell-mediated assembly and
      reorganization of collagen fibers was not limitless and only restricted to an
      appropriate ratio of cell number and collagen amount. The blocking of alpha2 or
      beta1-integrin function with specific antibodies significantly impeded the
      collagen-assembly effects. In vitro chondrogenesis or in vivo cartilage formation
      of human mesenchymal stem cells was also dependent on the interactions between
      cells and surrounding matrices. This method for three-dimensional fabricating
      collagen fibers may generally be applied to other biomaterials, when combined
      with surface modification or ligand addition for cell adhesion.

PMID- 17013868
TI  - Microtensile bond strength of composite resin to human enamel prepared using
      erbium: Yttrium aluminum garnet laser.
AB  - The Erbium: Yttrium Aluminum Garnet (YAG) laser used for preparation of cavity
      can alter the substrate and it could influence the bond strength of enamel. The
      aim of this in vitro study was to evaluate the influence of Er:YAG laser's energy
      using microtensile bond test. Three groups were obtained (cavity preparation) and
      each group was divided into two subgroups (adhesive system). After that the
      adhesive protocol was performed, sections with a cross-sectional area of 0.8 mm2
      (+/-0.2 mm2) were obtained. The specimens were mounted in a universal testing
      machine (0.5 mm/min). Statistical analysis showed a decrease in bond strength for
      lased groups (p < 0.01) and when the total-etching adhesive system was used the
      laser 300 mJ subgroup showed higher bond strength compared to the laser 250 mJ (p
      < 0.01). It was concluded that the cavities prepared using laser appear less
      receptive to adhesive procedures than conventional bur-cut cavities.

PMID- 17013869
TI  - Successes and failures in improving osteoporosis care after fragility fracture:
      results of a multiple-site clinical improvement project.
AB  - OBJECTIVE: To improve osteoporosis diagnosis and treatment of fragility fracture
      patient populations because osteoporosis care is provided infrequently to those
      patients, leaving them vulnerable to further fractures and increasing debility.
      METHODS: Osteoporosis experts from 11 US health systems participated in a
      clinical improvement project based on previously described successful
      osteoporosis care process redesigns. Participants were taught rapid cycle process
      improvement methods that are widely used in clinical improvement projects, and
      were supported in their efforts by the program coordinator. Measures of
      successful process development included establishing reliable referral from
      orthopedic fracture care to osteoporosis diagnosis and treatment, nurse
      coordination and monitoring of osteoporosis care, and use of process management
      software for registering patients and organizing work. RESULTS: Four sites were
      able to establish these critical referral and osteoporosis management processes.
      Two sites were partially successful in increasing orthopedic referrals to
      consultative care, but otherwise continued traditional care processes. Five were
      unsuccessful due to inability to implement 1 or more of these key process
      improvements. CONCLUSION: Reliable osteoporosis care for fracture patients is
      possible if traditional practice processes are replaced with more effective, well
      recognized approaches to chronic disease management.

PMID- 17013870
TI  - Patient treatment preferences for osteoporosis.
AB  - OBJECTIVE: To examine patient preferences for currently available and promising
      osteoporosis treatment options. METHODS: We recruited patients who had recently
      (within 2 weeks) undergone bone densitometry and were found to have osteoporosis.
      Consenting participants completed an Adaptive Conjoint Analysis questionnaire to
      determine their treatment preferences for oral bisphosphonates taken once per
      week, intravenous bisphosphonates administered every 3 months, intravenous
      bisphosphonates administered once per year, and subcutaneous recombinant human
      parathyroid hormone (rhPTH). We performed simulations based on respondents'
      values for route of administration, absolute reduction in risk of vertebral and
      hip fractures over 5 years, and risk of adverse effects to predict each
      respondent's treatment choice. RESULTS: The study sample included 201 women and
      11 men (median age 73). Patients' treatment preferences were strongly influenced
      by route of administration. Patients' preferred treatment option, across all
      simulations, was bisphosphonates. Among 80 treatment-naive participants, 52 (65%)
      preferred an annual infusion over oral weekly bisphosphonates. Participants with
      poorer perceived health status, those with a high perceived risk of future
      fracture, and participants preferring to treat health problems without doctors or
      prescription drugs were more likely to prefer an annual infusion over weekly
      pills. CONCLUSION: Patient preferences for osteoporosis treatment options are
      strongly influenced by route of administration. Therefore, despite the added
      benefits of rhPTH, patients' preferred treatment option for osteoporosis is
      bisphosphonates. Among those preferring bisphosphonates, many preferred annual
      infusions over weekly oral medications, emphasizing the need to incorporate
      individual patient preferences into treatment decisions for osteoporosis. The
      latter is especially important given the poor rates of long-term adherence to
      osteoporosis medications.

PMID- 17013871
TI  - Disability, social support, and distress in rheumatoid arthritis: results from a
      thirteen-year prospective study.
AB  - OBJECTIVE: To examine the strength and stability of the relationships between
      disease-related factors (joint tenderness, pain, and functional disability),
      social support, and distress over time, and to investigate to what extent disease
      related factors and social support can predict distress in short-term and long
      term rheumatoid arthritis (RA). METHODS: The study was a Dutch extension of the
      European Research on Incapacitating Diseases and Social Support and started with
      292 patients. After 5 waves of data collection, 129 patients remained. Composite
      measures were computed following the area under the curve approach. Interaction
      terms were computed between functional disability and social support
      satisfaction. Correlational and hierarchical regression analyses were performed.
      RESULTS: In patients with short-term RA, disease-related factors and social
      support were important in determining distress. Also, a buffering effect of
      social companionship was found. In total, 51% of the variance in distress in
      short-term RA could be explained primarily by mean distress over the previous
      years. In patients with long-term RA, disease-related factors remained important
      in determining distress, but to a lesser extent. Seventeen percent of the
      variance in distress in long-term RA could be explained primarily by mean
      distress over the years before. CONCLUSION: During the course of the disease,
      patients may learn to adjust to their disease and its consequences and are able
      to maintain a normal distress level. The effect of the disease on psychological
      distress decreased over the years. Some support for the buffering hypothesis of
      social support was found in short-term RA, but not in long-term RA.

PMID- 17013872
TI  - Repair of peripheral nerve defect with direct gradual lengthening of the proximal
      nerve stump in rats.
AB  - We investigated the effect of direct gradual lengthening on the proximal nerve
      stump and subsequent nerve regeneration in rats. A 10-mm-long nerve segment was
      resected from the sciatic nerve of each rat. The proximal nerve stump was
      directly lengthened at a rate of 1 mm/day using an original external nerve
      distraction device. Experiment I: After distraction periods of 10, 15, and 20
      days, the length of each nerve was evaluated, and the lengthened nerve stump was
      also examined by immunohistochemical analysis. Experiment II: After a distraction
      period of 20 days, both nerve stumps were refreshed and direct end-to-end
      neurorrhaphy was performed. For control, 10-mm nerve grafting was immediately
      performed after nerve resection. Nerve regeneration was evaluated
      electrophysiologically and histologically 7, 9, and 15 weeks after nerve
      resection in both groups. The whole proximal nerve stump, including the
      endoneurium and the axon, could be lengthened in proportion to the distraction
      period. There were no significant differences in motor nerve conduction velocity
      and tetanic muscle contraction force between both groups. Histologically, the
      total number of myelinated fibers was significantly greater in the nerve
      lengthening group than in the autografting group. This study demonstrated that
      the whole proximal nerve stump including the endoneurium and the axon could be
      lengthened by direct gradual distraction, and that this method might have
      potential application in the repair of peripheral nerve defects.

PMID- 17013873
TI  - A hierarchy of Runx transcription factors modulate the onset of chondrogenesis in
      craniofacial endochondral bones in zebrafish.
AB  - The Runx (runt-related) family of transcription factors are important regulators
      of cell fate decisions in early embryonic development, and in differentiation of
      tissues including blood, neurons, and bone. During skeletal development in
      mammals, while only Runx2 is essential for osteoblast differentiation, all family
      members seem to be involved in chondrogenesis. Runx2 and Runx3 control
      chondrocyte maturation. Both Runx1 and Runx2 are expressed early in mesenchymal
      condensations, but how they contribute to the initial stages of chondrocyte
      differentiation is unclear. Here we show that a hierarchy of Runx transcriptional
      regulation promotes the early program of chondrocyte differentiation from pre
      cartilage mesenchyme in the zebrafish head skeleton. We have previously
      characterized the zebrafish orthologs for all Runx genes. Zebrafish runx2 is
      duplicated, but not runx1 or runx3. In the work presented here, we determined the
      early expression pattern of the runx genes in the craniofacial region. The
      earliest expression detected was that of runx3 in the pharyngeal endoderm, then
      runx2a and b in mesenchymal condensations, and later runx1 in the epithelium.
      Using antisense morpholino knockdown analysis, we examined their respective
      activities in early chondrogenesis. Depletion of runx2b (but not runx2a) and
      runx3 severely compromised craniofacial cartilage formation. Because runx2b
      expression was abolished in Runx3 morphants, we propose that endodermal Runx3 has
      a role in influencing signaling activities from the endoderm to promote
      chondrocyte differentiation. We also show that, in contrast to data from mouse
      studies, zebrafish Runx1 is not required in the initial steps of chondrogenesis
      leading to endochondral bone formation.

PMID- 17013874
TI  - Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the
      somitogenesis clock of mice.
AB  - During segmentation (somitogenesis) in vertebrate embryos, somites form in a
      rostral-to-caudal sequence according to a species-specific rhythm called the
      somitogenesis clock. The expression of genes participating in somitogenesis
      oscillates in the presomitic mesoderm (PSM) in time with this clock. We
      previously reported that the Dact1 gene (aka Dpr1/Frd1/ThyEx3), which encodes a
      Dishevelled-binding intracellular regulator of Wnt signaling, is prominently
      expressed in the PSM as well as in a caudal-rostral gradient across the somites
      of mouse embryos. This observation led us to examine whether Dact1 expression
      oscillates in the PSM. We have found that Dact1 PSM expression does indeed
      oscillate in time with the somitogenesis clock. Consistent with its known
      signaling functions and with the "clock and wavefront" model of signal regulation
      during somitogenesis, the oscillation of Dact1 occurs in phase with the Wnt
      signaling component Axin2, and out of phase with the Notch signaling component
      Lfng.

PMID- 17013876
TI  - Localization and requirement for Myosin II at the dorsal-ventral compartment
      boundary of the Drosophila wing.
AB  - As organisms develop, their tissues can become separated into distinct cell
      populations through the establishment of compartment boundaries. Compartment
      boundaries have been discovered in a wide variety of tissues, but in many cases
      the molecular mechanisms that separate cells remain poorly understood. In the
      Drosophila wing, a stripe of Notch activation maintains the dorsal-ventral
      compartment boundary, through a process that depends on the actin cytoskeleton.
      Here, we show that the dorsal-ventral boundary exhibits a distinct accumulation
      of Myosin II, and that this accumulation is regulated downstream of Notch
      signaling. Conversely, the dorsal-ventral boundary is depleted for the Par-3
      homologue Bazooka. We further show that mutations in the Myosin heavy chain
      subunit encoded by zipper can impair dorsal-ventral compartmentalization without
      affecting anterior-posterior compartmentalization. These observations identify a
      distinct accumulation and requirement for Myosin activity in dorsal-ventral
      compartmentalization, and suggest a novel mechanism in which contractile tension
      along an F-actin cable at the compartment boundary contributes to
      compartmentalization.

PMID- 17013875
TI  - Genetic dissection of a stem cell niche: the case of the Drosophila ovary.
AB  - In this work, we demonstrate a powerful new tool for the manipulation of the
      stromal component of a well-established Drosophila stem cell niche. We have
      generated a bric-a-brac 1 (bab1)-Gal4 line that drives UAS expression in many
      somatic ovary cell types from early larval stages. Using this Gal4 line, we could
      effectively induce FLP/FRT-mediated recombination in the stromal cells of the
      ovarian germline stem cell niche. Mutant clones were observed in the developing
      ovary of larvae and pupae, including in somatic cell types that do not divide in
      the adult, such as the cap cells and the terminal filament cells. Exploiting the
      ability of bab1-Gal4 to generate large clones, we demonstrate that bab1-Gal4 is
      an effective tool for analyzing stem cell niche morphogenesis and cyst formation
      in the germarium. We have identified a novel requirement for engrailed in the
      correct organization of the terminal filaments. We also demonstrate an
      involvement for integrins in cyst formation and follicle cell encapsulation.
      Finally using bab1-Gal4 in conjunction with the Gal80 system, we show that while
      ectopic dpp expression from stromal cells is sufficient to induce hyperplastic
      stem cell growth, neither activation nor inactivation of the BMP pathway within
      stromal cells affects germline stem cell maintenance.

PMID- 17013878
TI  - Zebrafish pax5 regulates development of the utricular macula and vestibular
      function.
AB  - The zebrafish otic vesicle initially forms with only two sensory epithelia, the
      utricular and saccular maculae, which primarily mediate vestibular and auditory
      function, respectively. Here, we test the role of pax5, which is preferentially
      expressed in the utricular macula. Morpholino knockdown of pax5 disrupts
      vestibular function but not hearing. Neurons of the statoacoustic ganglion (SAG)
      develop normally. Utricular hair cells appear to form normally but a variable
      number subsequently undergo apoptosis and are extruded from the otic vesicle.
      Dendrites of the SAG persist in the utricle but become disorganized after hair
      cell loss. Hair cells in the saccule develop and survive normally. Otic
      expression of pax5 requires pax2a and fgf3, mutations in which cause vestibular
      defects, albeit by distinct mechanisms. Thus, pax5 works in conjunction with fgf3
      and pax2a to establish and/or maintain the utricular macula and is essential for
      vestibular function.

PMID- 17013879
TI  - The mother superior mutation ablates foxd3 activity in neural crest progenitor
      cells and depletes neural crest derivatives in zebrafish.
AB  - The zebrafish mutation mother superior (mosm188) leads to a depletion of neural
      crest (NC) derivatives including the craniofacial cartilage skeleton, the
      peripheral nervous system (sympathetic neurons, dorsal root ganglia, enteric
      neurons), and pigment cells. The loss of derivatives is preceded by a reduction
      in NC-expressed transcription factors, snail1b, sox9b, sox10, and a specific loss
      of foxd3 expression in NC progenitor cells. We employed genetic linkage analysis
      and physical mapping to place the mosm188 mutation on zebrafish chromosome 6 in
      the vicinity of the foxd3 gene. Furthermore, we found that mosm188 does not
      complement the sym1/foxd3 mutation, indicating that mosm188 resides within the
      foxd3 locus. Injection of PAC clones containing the foxd3 gene into mosm188
      embryos restored foxd3 expression in NC progenitors and suppressed the mosm188
      phenotype. However, sequencing the foxd3 transcribed area in mosm188 embryos did
      not reveal nucleotide changes segregating with the mosm188 phenotype, implying
      that the mutation most likely resides outside the foxd3-coding region. Based on
      these findings, we propose that the mosm188 mutation perturbs a NC-specific foxd3
      regulatory element. Further analysis of mosm188 mutants and foxd3 morphants
      revealed that NC cells are initially formed, suggesting that foxd3 function is
      required to maintain the pool of NC progenitors.

PMID- 17013880
TI  - MicroRNA expression during chick embryo development.
AB  - MicroRNAs (miRNAs) are small, abundant, noncoding RNAs that modulate protein
      abundance by interfering with target mRNA translation or stability. miRNAs are
      detected in organisms from all domains and may regulate 30% of transcripts in
      vertebrates. Understanding miRNA function requires a detailed determination of
      expression, yet this has not been reported in an amniote species. High-throughput
      whole mount in situ hybridization was performed on chicken embryos to map
      expression of 135 miRNA genes including five miRNAs that had not been previously
      reported in chicken. Eighty-four miRNAs were detected before day 5 of
      embryogenesis, and 75 miRNAs showed differential expression. Whereas few miRNAs
      were expressed during formation of the primary germ layers, the number of miRNAs
      detected increased rapidly during organogenesis. Patterns highlighted cell-type,
      organ or structure-specific expression, localization within germ layers and their
      derivatives, and expression in multiple cell and tissue types and within sub
      regions of structures and tissues. A novel group of miRNAs was highly expressed
      in most tissues but much reduced in one or a few organs, including the heart.
      This study presents the first comprehensive overview of miRNA expression in an
      amniote organism and provides an important foundation for investigations of miRNA
      gene regulation and function.

PMID- 17013881
TI  - Identification of genes potentially involved in the acquisition of androgen
      independent and metastatic tumor growth in an autochthonous genetically
      engineered mouse prostate cancer model.
AB  - BACKGROUND: A major focus of prostate cancer research has been to identify genes
      that are deregulated during tumor progression, potentially providing diagnostic
      markers and therapeutic targets. METHODS: We have employed serial analysis of
      gene expression (SAGE) and microarray hybridization to identify alterations that
      occur during malignant transformation in the Transgenic Adenocarcinoma of the
      Mouse Prostate (TRAMP) model. Many of these alterations were validated by real
      time PCR (rtPCR). RESULTS: We identified several hundred mRNAs that were
      deregulated. Cluster analysis of microarray profiles with samples from various
      stages of the disease demonstrated that androgen-independent (AI) primary tumors
      are similar to metastases; 180 transcripts have expression patterns suggesting an
      involvement in the genesis of late-stage tumors, and our data support a role for
      phospholipase A2 group IIA in the acquisition of their highly aggressive
      characteristics. CONCLUSIONS: Our analyses identified well-characterized genes
      that were previously known to be involved in prostate cancer, validating our
      study, and also uncovered transcripts that had not previously been implicated in
      prostate cancer progression.

PMID- 17013882
TI  - Therapy of multidrug resistant human prostate tumors in the prostate of nude mice
      by simultaneous targeting of the epidermal growth factor receptor and vascular
      endothelial growth factor receptor on tumor-associated endothelial cells.
AB  - BACKGROUND: Inhibiting epidermal growth factor receptor (EGF-R) and vascular
      endothelial growth factor receptor (VEGF-R) activation with AEE788 can decrease
      prostate cancer (CaP) growth/progression. We determined whether tumor cells or
      tumor-associated endothelial cells were the primary target by treating multidrug
      resistant (MDR) CaP growing in the prostate of nude mice. METHODS: MDR human CaP
      cells with 30-fold increased taxane-resistance were implanted into nude mouse
      prostates. After 2 weeks, mice were randomized to control, paclitaxel, AEE788,
      and AEE788/paclitaxel for 10 weeks. Mice were necropsied and tumors stained.
      RESULTS: AEE788 or AEE788 plus paclitaxel significantly reduced tumor incidence
      and tumor weight, and eradicated lymph node metastasis. Inhibiting VEGF-R and EGF
      R phosphorylation induced apoptosis of tumor-associated endothelial cells causing
      a second apoptotic wave of surrounding tumor cells. CONCLUSION: Inhibiting VEGF-R
      and EGF-R activation on tumor-associated endothelial cells with AEE788 combined
      with paclitaxel can bypass CaP cell resistance and prevent lymph node metastasis.

PMID- 17013883
TI  - Ginsenoside Re promotes human sperm capacitation through nitric oxide-dependent
      pathway.
AB  - The regulation of sperm capacitation is important for successful fertilization.
      Ginsenosides, the biologically effective components of ginseng, have been found
      to enhance intracellular nitric oxide (NO) production and the latter has recently
      been indicated to play a significant role in modulation of sperm functions. We
      investigated the effect of Ginsenoside Re on human sperm capacitation in vitro
      and the mechanism by which the Ginsenosides play their roles. Spermatozoa were
      separated by Percoll and incubated with 0, 1, 10, or 100 microM of Ginsenoside
      Re. The percentages of spontaneous and lysophosphatidylcholine (LPC)-induced
      acrosome reaction (AR), as a measure of sperm capacitation, were assayed with
      fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA). The
      intracellular cGMP level was measured by [(3)H] cGMP radioimmunoassay system. The
      results showed that the percentages of both spontaneous and LPC-induced AR and
      intracellular cGMP level were significantly enhanced by Ginsenoside Re with a
      concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor,
      mimicked the effects of Ginsenoside Re. And pretreatment with a NOS inhibitor
      N(omega)-nitro-l-arginine methyl ester (L-NAME, 100 microM) or a NO scavenger N
      acetyl-l-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside Re.
      Furthermore, the AR-inducing effect of Ginsenoside Re was significantly reduced
      in the presence of the soluble guanylate cyclase inhibitor LY83583 or cGMP
      dependent protein kinase (PCK) inhibitor KT5823, whereas addition of the cGMP
      analogue 8-Br-cGMP significantly increased the AR of human spermatozoa. Data
      suggested that Ginsenoside Re is beneficial to sperm capacitation and AR, and
      that the effect is accomplished through NO/cGMP/PKG pathway.

PMID- 17013884
TI  - The RNA binding protein Zfp36l1 is required for normal vascularisation and post
      transcriptionally regulates VEGF expression.
AB  - The Zfp36l1 gene encodes a zinc finger-containing mRNA binding protein implicated
      in the posttranscriptional control of gene expression. Mouse embryos homozygous
      for a targeted mutation in the Zfp36l1 locus died mid-gestation and exhibited
      extraembryonic and intraembryonic vascular abnormalities and heart defects. In
      the developing placenta, there was a failure of the extraembryonic mesoderm to
      invaginate the trophoblast layer. The phenotype was associated with an elevated
      expression of vascular endothelial growth factor (VEGF)-A in the embryos and in
      embryonic fibroblasts cultured under conditions of both normoxia and hypoxia.
      VEGF-A overproduction by embryonic fibroblasts was not a consequence of changes
      in Vegf-a mRNA stability; instead, we observed enhanced association with
      polyribosomes, suggesting Zfp36l1 influences translational regulation. These data
      implicate Zfp36l1as a negative regulator of Vegf-a gene activity during
      development.

PMID- 17013885
TI  - Cultured endothelial cells display endogenous activation of the canonical Wnt
      signaling pathway and express multiple ligands, receptors, and secreted
      modulators of Wnt signaling.
AB  - A growing body of evidence implicates Wnt signaling in the control of
      angiogenesis. To better understand the role of the Wnt/beta-catenin pathway in
      endothelial cells (EC), we examined endogenous signaling activity and signaling
      component expression in vascular cells. We observed stabilization of cytosolic
      beta-catenin and activation of a T-cell factor (TCF) -luciferase promoter,
      hallmarks of canonical Wnt signaling activity, in cultured EC. This activity was
      increased in subconfluent EC, which are known to display characteristics of
      angiogenic EC, compared with confluent EC, which have a more differentiated
      phenotype. Endogenous TCF activity was inhibited by transfection with a secreted
      inhibitor of canonical Wnt signaling. A systematic analysis of Wnt, Fzd, SFRP,
      and Dkk gene expression in human EC (cultured and freshly isolated), smooth
      muscle cells (cultured), and aorta demonstrated that numerous Wnt signaling
      components are expressed by vascular cells. We conclude that Wnt signaling
      components are expressed and active in cultured EC.

PMID- 17013887
TI  - Time-dependent effects of fatty acids on skeletal muscle metabolism.
AB  - Increased plasma levels of free fatty acids (FFA) occur in states of insulin
      resistance such as type 2 diabetes mellitus, obesity, and metabolic syndrome.
      These high levels of plasma FFA seem to play an important role for the
      development of insulin resistance but the mechanisms involved are not known. We
      demonstrated that acute exposure to FFA (1 h) in rat incubated skeletal muscle
      leads to an increase in the insulin-stimulated glycogen synthesis and glucose
      oxidation. In conditions of prolonged exposure to FFA, however, the insulin
      stimulated glucose uptake and metabolism is impaired in skeletal muscle. In this
      review, we discuss the differences between the effects of acute and prolonged
      exposure to FFA on skeletal muscle glucose metabolism and the possible mechanisms
      involved in the FFA-induced insulin resistance.

PMID- 17013888
TI  - Development and evaluation of the electromagnetic hypersensitivity questionnaire.
AB  - Electromagnetic hypersensitivity (EHS) syndrome is usually defined as a condition
      where an individual experiences adverse health effects that he or she believes is
      due to exposure to objects that emit electromagnetic fields. The aim of this
      study was to develop a questionnaire that would identify the key symptoms
      associated with EHS and determine how often these symptoms occur in the general
      population of the United Kingdom. In the pilot study, an EHS questionnaire was
      developed and tested. In Study 1 the EHS questionnaire was revised and sent to a
      randomly selected sample of 20,000 people. Principal components analysis of the
      symptoms resulted in eight subscales: neurovegetative, skin, auditory, headache,
      cardiorespiratory, cold related, locomotor, and allergy related symptoms. Study 2
      established the validity of the questionnaire in that EHS individuals showed a
      higher severity of symptoms on all subscales compared to the control group. The
      two key results of this study were the development of a scale that provides an
      index of the type and intensity of symptoms commonly experienced by people
      believing themselves to be EHS and a screening tool that researchers can use to
      pre-select the most sensitive individuals to take part in their research.

PMID- 17013886
TI  - Neurotrophin-3 ameliorates sensory-motor deficits in Er81-deficient mice.
AB  - Two factors, the ETS transcription factor ER81 and skeletal muscle-derived
      neurotrophin-3 (NT3), are essential for the formation of muscle spindles and the
      function of spindle afferent-motoneuron synapses in the spinal cord. Spindles
      either degenerate completely or are abnormal, and spindle afferents fail to
      project to spinal motoneurons in Er81 null mice; however, the interactions
      between ER81 and NT3 during the processes of afferent neuron and muscle spindle
      development are poorly understood. To examine if overexpression of NT3 in muscle
      rescues spindles and afferent-motoneuron connectivity in the absence of ER81, we
      generated myoNT3;Er81(-/-) double-mutant mice that selectively overexpress NT3 in
      muscle in the absence of ER81. Spindle reflex arcs in myoNT3;Er81(-/-) mutants
      differed greatly from Er81 null mice. Muscle spindle densities were greater and
      more afferents projected into the ventral spinal cord in myoNT3;Er81(-/-) mice.
      Spindles of myoNT3;Er81(-/-) muscles responded normally to repetitive muscle
      taps, and the monosynaptic inputs from Ia afferents to motoneurons, grossly
      reduced in Er81(-/-) mutants, were restored to wild-type levels in myoNT3;Er81(-/
      ) mice. Thus, an excess of muscle-derived NT3 reverses deficits in spindle
      numbers and afferent function induced by the absence of ER81. We conclude that
      muscle-derived NT3 can modulate spindle density and afferent-motoneuron
      connectivity independently of ER81.

PMID- 17013889
TI  - Muscle activation assessment: effects of method, stimulus number, and joint
      angle.
AB  - Activation capacity has traditionally been assessed using the interpolated twitch
      technique (ITT) and central activation ratio (CAR). However, the quantitative
      agreement of the two methods and the physiological mechanisms underpinning any
      possible differences have not been fully elucidated. The aim of this study was to
      compare and assess the sensitivity of the ITT and CAR to potential errors
      introduced by (1) evoking inadequate force, by manipulating the number of
      stimuli, and (2) neglecting differences in series elasticity between conditions,
      by manipulating joint angle. Ten subjects performed knee extension contractions
      at 30 degrees and 90 degrees knee-joint angles during which the ITT and CAR
      methods were applied using 1, 2, 4, and 8 electrical stimuli. Joint angle
      influenced the ITT outcome with higher values taken at 90 degrees (P < 0.05),
      while the number of stimuli influenced the CAR outcome with a higher number of
      stimuli yielding lower values (P < 0.05). For any given joint angle and stimulus
      number, the CAR method produced higher activation values than the ITT method by
      8%-16%. Therefore, in the quantification of voluntary drive with the ITT and CAR
      methods consideration should be given not only to the number of stimuli applied
      but also to the effect of series elasticity due to joint-angle differences, since
      these factors may differently affect the outcome of the calculation, depending on
      the approach followed.

PMID- 17013890
TI  - Dietary treatment of gluten neuropathy.
AB  - We studied the effect of a gluten-free diet in patients with idiopathic
      sensorimotor axonal neuropathy and circulating antigliadin antibodies.
      Consecutive patients underwent baseline neurophysiological assessment and were
      offered a gluten-free diet. Those who went on the diet formed the intention-to
      treat group and those who did not were the control group. Repeat
      neurophysiological assessment and subjective evaluation of neuropathy symptoms
      were performed at 1 year. A total of 35 patients participated in the study, with
      25 patients going on the diet and 10 not doing so. There was a significant
      difference in the change of sural sensory action potentials (pre-defined primary
      endpoint), with evidence of improvement in the intention-to-treat group and
      deterioration in the control group. Subjective change in neuropathy symptoms also
      showed significant differences, with patients in the intention-to-treat group
      reporting improvement and those in the control group reporting deterioration.
      Gluten-free diet may thus be a useful therapeutic intervention for patients with
      gluten neuropathy.

PMID- 17013891
TI  - Expression of the AmphiTcf gene in amphioxus: insights into the evolution of the
      TCF/LEF gene family during vertebrate evolution.
AB  - T-cell factor (TCF) and lymphoid enhancer factors (LEF) genes encode proteins
      that are transcription factors mediating beta-catenin/Wnt signaling. Whereas
      mammals have four such genes, the Florida amphioxus (Branchiostoma floridae)
      apparently has only one such gene (AmphiTcf). From cleavage through early
      gastrula, cytoplasmic maternal transcripts of this gene are localized toward the
      animal pole. In gastrulae, AmphiTcf expression begins in the mesendoderm. In
      neurulae, there is expression in the pharynx, hindgut, anterior notochord,
      somites, and at the anterior end of the neural plate. In early larvae, expression
      is detectable in the floor of the diencephalon, notochord, tail bud, forming
      somites, pharynx, and ciliated pit (a presumed homolog of the vertebrate
      adenohypophysis). Phylogenetic analysis of TCF/LEF proteins placed AmphiTcf as
      the sister group of a clade comprising vertebrate Tcf1, Lef1, Tcf3, and Tcf4.
      Comparison of developmental expression for amphioxus AmphiTcf and vertebrate
      TCF/LEF genes indicates that this gene family has undergone extensive
      subfunctionalization and neofunctionalization during vertebrate evolution.

PMID- 17013892
TI  - Quantitative volumetric analysis of cardiac morphogenesis assessed through micro
      computed tomography.
AB  - We present a method to generate quantitative embryonic cardiovascular volumes at
      extremely high resolution without tissue shrinkage using micro-computed
      tomography (Micro-CT). A CT dense polymer (Microfil, Flow Tech, Inc.) was used to
      perfuse avian embryonic hearts from Hamburger and Hamilton stage (HH) 15 through
      HH36, which solidified to create a cast within the luminal space. Hearts were
      then scanned at 10.5 mum(3) voxel resolution using a VivaCT scanner, digital
      slices were contoured for regions of interest, and computational analysis was
      conducted to quantify morphogenetic parameters. The three-dimensional morphology
      was compared with that of scanning electron microscopy (SEM) images and serial
      section reconstruction of similarly staged hearts. We report that Microfil
      perfused hearts swelled to maximum end-diastolic volume with negligible shrinking
      after polymerization. Comparison to SEM revealed good agreement of cardiac
      chamber proportions and intracardiac tissue structures (i.e., valves and septa)
      at the stages of development assessed. Quantification of changes in chamber
      volume over development revealed several notable results that confirm earlier
      hypotheses. Heart chamber volumes grow over two orders of magnitude during the 1
      week developmental period analyzed. The atrioventricular canal comprised a
      significant proportion of the early heart volume. While left atrium/left
      ventricular volume ratios approached 1 in later development, right atrium/right
      ventricle ratios increase to over 2.5. Quantification of trabeculation patterns
      confirmed that the right and left ventricles are similarly trabeculated before
      HH27, after which the right ventricle became quantitatively coarser than that of
      the left ventricle. These results demonstrate that Micro-CT can be used to image
      and quantify cardiovascular structures during development.

PMID- 17013893
TI  - Incidence patterns of soft tissue sarcomas, regardless of primary site, in the
      surveillance, epidemiology and end results program, 1978-2001: An analysis of
      26,758 cases.
AB  - Soft tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that show
      a broad range of differentiation that may reflect etiologic distinction. Routine
      tabulations of STS are not morphology-specific. Further, the lack of inclusion of
      sarcomas arising in all organs in most standard evaluations underestimates the
      true rates. We analyzed the 1978-2001 Surveillance, Epidemiology and End Results
      program incidence rates of STS regardless of primary site, except bones and
      joints, using the 2002 criteria of the WHO classification. There were 26,758
      cases available for analysis. Leiomyosarcomas accounted for 23.9%, malignant
      fibrous histiocytomas 17.1%, liposarcomas 11.5%, dermatofibrosarcomas 10.5%,
      rhabdomyosarcomas 4.6% and angiosarcomas 4.1%. Almost half (47.9%) of the
      sarcomas arose in the soft tissues, 14.0% in the skin and 7.0% in the uterus.
      Overall, incidence rates were highest among black women (6.26/100,000 woman
      years) and the lowest among white women (4.60/100,000). Age-adjusted rates
      increased at 1.2% and 0.8% per year among white males and females, respectively,
      both trends statistically significant, while rates among blacks declined
      slightly. About 40% of leiomyosarcomas among women were uterine in origin, with a
      black/white rate ratio of 1.7. This rate ratio increased to 2.0 when we accounted
      for the lower prevalence of intact uteri among black compared to white women.
      Total STS rates rose exponentially with age. Rates for both uterine
      leiomyosarcoma and dermatofibrosarcoma increased rapidly during the childbearing
      years, peaking at about age 40 and 50, respectively. Incidence patterns of STS
      varied markedly by histologic type, supporting the notion that these tumors may
      be etiologically distinct.

PMID- 17013894
TI  - SULT1A1 genotype and susceptibility to colorectal cancer.
AB  - Several procarcinogens that are present in cooked red meat and tobacco smoke are
      substrates for sulfotransferase 1A1 (SULT1A1). The association between
      environmental exposures and colorectal cancer risk may be modified by individual
      differences in the metabolism. Thus, we investigated the effect of a common
      polymorphism in the SULT1A1 gene associated with decreased enzyme activity on the
      susceptibility to colorectal cancer in a population-based case-control study.
      Patients (505) and 604 age- and sex-matched controls provided detailed risk
      factor information and were genotyped for SULT1A1 G638A using a fluorescence
      based melting curve analysis method. Multivariate logistic regression analysis
      was used to estimate colorectal cancer risk associated with environmental
      exposures by SULT1A1 genotype. SULT1A1 genotype was not an independent risk
      factor for colorectal cancer. Risk of colorectal cancer associated with frequent
      consumption of red meat was significantly elevated among carriers of the
      SULT1A1*2 allele but not increased among subjects with the SULT1A1*1/*1 genotype
      (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.1 and OR 1.0, 95% CI 0.5
      2.1, respectively). Colorectal cancer risk associated with 30+ pack-years of
      active smoking was higher among carriers of the SULT1A1*2 allele (OR 1.7, 95% CI
      1.0-3.2) than among individuals with the SULT1A1*1/*1 genotype (OR 1.1, 95% CI
      0.6-2.1). Our results do not support a main effect of SULT1A1 genotype with
      regard to colorectal cancer but suggest that individuals with the low activity
      SULT1A1*2 allele may be at higher risk following carcinogen exposure than those
      with the SULT1A1*1/*1 genotype.

PMID- 17013895
TI  - Novel combination therapy against metastatic and androgen-independent prostate
      cancer by using gefitinib, tamoxifen and etoposide.
AB  - In this study, we evaluated, for the first time, the antiproliferative and
      cytotoxic effects induced by a combination of a selective epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor, gefitinib, with other chemotherapeutic
      drugs including estrogen receptor-beta (ER-beta) antagonist (tamoxifen) and
      topoisomerase II inhibitor (etoposide) on some metastatic prostate cancer (PC)
      cell lines. Immunohistochemial analyses revealed that EGFR expression was
      enhanced in 38% of primary prostatic adenocarcinomas (Gleason scores 4-10) as
      compared to the corresponding normal tissues of the same prostate gland from 32
      PC patients. The RT-PCR and Western blot data have also indicated the higher
      expression levels of EGFR and ER-beta transcripts and proteins in metastatic
      LNCaP, DU145 and PC3 cells relative to nonmalignant normal prostate cells.
      Moreover, the results from MTT and FACS analyses revealed that the drugs, alone
      or in combination at lower concentrations, inhibited the growth of 17beta
      estradiol (E2) plus EGF and serum-stimulated androgen-responsive LNCaP-C33 and
      androgen-independent LNCaP-C81, DU145 and PC3 cells. Importantly, the combined
      gefitinib, tamoxifen and etoposide also caused a higher rate of apoptotic death
      of PC cells as compared to single agents. The cytotoxic effects induced by these
      drugs in PC3 cells appear to be mediated through the accumulation of cellular
      ceramide and activation of caspase cascades via a mitochondrial pathway. These
      findings indicate that the combined use of inhibitors of EGF-EGFR and E2-ER-beta
      signaling with etoposide, which act by increasing the cellular ceramide levels
      and caspase activity, represents a promising strategy for a more effective
      treatment of metastatic PC forms.

PMID- 17013896
TI  - Inactivation of RASSF2A by promoter methylation correlates with lymph node
      metastasis in nasopharyngeal carcinoma.
AB  - RASSF2 can bind directly to K-Ras and function as a negative effector of Ras
      protein. RASSF2A is the only isoform of RASSF2 that contains CpG islands in its
      promoter and it has been reported to be inactivated by its promoter methylation
      in several human cancers. In the present study, we investigated the correlation
      of RASSF2A expression with its promoter methylation in nasopharyngeal carcinoma
      (NPC). Expression of RASSF2A was down-regulated in 80% (4/5) of NPC cell lines.
      Decreased RASSF2A expression was also observed in NPC primary tumors compared
      with normal nasopharyngeal epithelia. Promoter methylation of RASSF2A could be
      detected in all the RASSF2A-silenced cell lines (4/5) of the NPC cell lines and
      50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF2A
      methylated cases showed a significantly lower level of RASSF2A expression than
      unmethylated cases. Loss of RASSF2A expression can be greatly restored by the
      methyltransferase inhibitor 5-aza-dC in NPC cell lines. In addition, patients
      with methylated RASSF2A presented a higher frequency of lymph node metastasis (p
      < 0.05). Ectopic expression of RASSF2A in RASSF2A-silenced and -methylated NPC
      cell line CNE2 shows that RASSF2A could inhibit cell cycle progression, colony
      formation and cell migration, which provided further evidence that RASSF2A is a
      candidate tumor suppressor gene. In conclusion, RASSF2A, a candidate tumor
      suppressor gene (TSG), is frequently inactivated by its promoter methylation and
      this aberrant methylation correlates with lymph node metastasis in NPC.

PMID- 17013897
TI  - PSA doubling time predicts the outcome after active surveillance in screening
      detected prostate cancer: results from the European randomized study of screening
      for prostate cancer, Sweden section.
AB  - This study reports the outcome of active surveillance in men with PSA screening
      detected prostate cancer (PC), and PSA doubling time (PSADT) was evaluated as a
      predictor of selecting patients to active treatment or surveillance. On December
      31, 1994, 10,000 men were randomized to biennial PSA testing. Through to December
      2004, a total of 660 men were diagnosed with PC, of whom 270 managed with initial
      surveillance. Of these 270 patients, 104 (39%) received active treatment during
      follow-up, 70 radical prostatectomy, 24 radiation and 10 endocrine treatment.
      Those who received active treatment during follow-up (mean 63 months) were
      significantly younger (62.6 vs. 65.5 years, p < 0.0001) and had a shorter PSADT
      (3.7 vs. 12 years, p < 0.0001). PSA relapse was observed in 9 of 70 patients who
      received RRP during a mean follow-up of 37 months. Seven of these nine PSA
      relapses were in the patients with preoperative PSADT < 2 years. None of the 37
      operated patients with a PSADT > 4 years had a PSA relapse. In a Cox regression
      analysis adjusted for PSA, ratio-free PSA and amount of cancer in biopsy, only
      the preoperative PSADT was statistically significant predictor of PSA relapse in
      p = 0.031. The optimal candidate for surveillance is a man with early, low-grade,
      low-stage PC and a PSADT > 4 years. In younger men with a PSADT of less than 4
      years, surveillance does not seem to be a justified alternative, and patient
      should be informed about the risk with such an approach.

PMID- 17013898
TI  - Correlation between hypermethylation of the RASSF2A promoter and K-ras/BRAF
      mutations in microsatellite-stable colorectal cancers.
AB  - Recently, RASSF2A was identified as a potential tumor suppressor epigenetically
      inactivated in human cancers. Here, we evaluated the methylation status of
      RASSF2A in colorectal cancer (CRC) and analyzed its correlation with K-ras/BRAF
      mutations, microsatellite instability status and other clinicopathological
      features. Using methylation-specific PCR and bisulfite sequencing, we analyzed
      the methylation status in primary CRC, adenomas and corresponding normal tissues
      and then compared it with the presence of K-ras and BRAF mutations. We also
      examined the expression and methylation status of RASSF2A in CRC cell lines. We
      found that aberrant methylation of RASSF2A promoter regions is associated with
      gene silencing in CRC cell lines. In primary CRC, the frequency of RASSF2A
      methylation was 72.6%, and it was found in 16 of 16 (100%) adenomas. In addition,
      there was a positive correlation between K-ras/BRAF mutations and RASSF2A
      methylation in primary CRC. Furthermore, a significant positive correlation
      between K-ras/BRAF mutations and RASSF2A methylation was also observed in
      microsatellite-stable (p = 0.033) and distal CRC (p = 0.025). These results show
      that RASSF2A methylation is a frequent event in colorectal tumorigenesis and
      positively correlates with K-ras/BRAF mutation in microsatellite-stable or distal
      CRC.

PMID- 17013899
TI  - Concomitant chemo-radiotherapy and local dose of radiation as risk factors for
      second malignant neoplasms after solid cancer in childhood: a case-control study.
AB  - Radiotherapy and chemotherapy are associated with an increased risk of a second
      malignant neoplasm (SMN) after a cancer during childhood. This study specified
      the dose-effect relationship between radiotherapy, chemotherapy and the risk of a
      SMN, and investigated the effect of chemo-radiotherapy on the risk of SMN. A case
      control study nested in a European cohort of 4,581 patients treated for a solid
      cancer during childhood was conducted. One hundred and fifty three cases with a
      SMN and 442 controls were matched according to sex, age at first cancer, calendar
      year, type of first cancer and follow-up. The local radiation dose was estimated
      at the site of the SMN, for each case and at the same site, for the matched
      controls. The local dose of radiation significantly increased the risk of a SMN.
      The best model was linear with an excess relative risk per Gray equal to 0.13
      (95% CI, 0.06; 0.26). Any chemotherapy significantly increased the risk of a SMN,
      odd ratio(adjusted) (OR(adjusted)) = 2.4 (95% confidence interval (95% CI), 1.4
      4.1), but no dose-effect relationship was observed between any drug category and
      the risk of a SMN. Patients who had received concomitant chemo-radiotherapy were
      significantly more at risk of developing a SMN than patients who had been treated
      with sequential chemo-radiotherapy, even after adjustment for the local dose of
      radiation and the 6 most frequently administered drugs, OR(adjusted) = 2.3
      (95%CI, 1.1-4.8). Radiation was found to be the foremost treatment-related risk
      factor for the occurrence of a SMN. Compared to sequential treatment, concomitant
      chemo-radiotherapy may lead to a higher risk of a SMN.

PMID- 17013900
TI  - Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by
      IL-10 in the EBV-positive NK lines SNK6 and KAI3.
AB  - Extranodal, nasal NK/T-cell lymphomas are regularly Epstein-Barr virus (EBV)
      positive, with a type II latency pattern, expressing thus EBNA-1 and LMP1. The
      contribution of EBV to the tumor development is not known. Similarly to normal
      natural killer (NK) cells, cell lines derived from malignancies with a NK
      phenotype require IL-2 for in vitro proliferation. In our effort to explore the
      contribution of EBV, particularly the role of the LMP1 protein, to the
      pathogenesis of the NK lymphoma we found that its expression, studied in the NK
      lines SNK6 and KAI3, depended on the supply of IL-2 or other cytokines. In the
      absence of IL-2 other cytokines, such as IL-10 and IFN-gamma, could maintain
      LMP1, but the cells did not proliferate. When grown in IL-2, the SNK6 cells
      produced IL-10 and IFN-gamma, and these cytokines mediated the expression of
      LMP1. IL-10 treatment enhanced, while IFN-gamma receptor blocking antibody
      reduced, the expression of CD25 and CD54 in the EBV-positive, but not in the EBV
      negative lines. IL-10 treated cells required lower amount of IL-2 for
      proliferation compared to the untreated cells. This effect was seen only with the
      EBV-positive NK lines in which LMP1 and CD25 were concomitantly upregulated. By
      this mechanism EBV could have an important role in the development of NK lymphoma
      since the inflammatory component in the tumor tissue can provide these cytokines.

PMID- 17013901
TI  - Expression of multiple human endogenous retrovirus surface envelope proteins in
      ovarian cancer.
AB  - Individual classes of human endogenous retrovirus (HERV) genes and proteins are
      expressed in cancer, but expression of more than one type of HERV is rare. We
      report here the expression of multiple HERV genes and proteins in ovarian cell
      lines and tissues. Expression of HERV-K env mRNA was greater in ovarian
      epithelial tumors than in normal ovarian tissues (N = 254). The expression of
      this protein on the surface and in the cytoplasm of ovarian cancer cells was
      confirmed using anti-HERV-K specific antibody by flow cytometric analysis. The
      frequency of expression of HERV-K env protein in multitissue microarrays (N =
      641) was determined by immunohistochemistry and a significant correlation with
      tumor histotype was found. A significantly increased expression of HERV-K was
      observed in tumors with low malignant potential and low grade, relative to
      expression in normal ovarian tissues. The increase in expression of HERV-K env
      protein took place in a stepwise fashion in serous papillary adenocarcinoma.
      Interestingly, we found that other classes of HERV env mRNAs, including ERV3 and
      HERV-E, are expressed in the same ovarian cancer tissues that expressed HERV-K.
      Furthermore, anti-HERV antibodies including anti-ERV3 (30%), anti-HERV-E (40%)
      and anti-HERV-K (55%) were detected in patients with ovarian cancer, but not in
      normal female controls. HERV env proteins are frequently transcribed and
      translated in ovarian epithelial tumors, and multiple HERV families are
      detectable in ovarian cancer. HERV env proteins, and especially those expressed
      on the cell surface, may serve as novel tumor targets for detection, diagnosis
      and immunotherapy of ovarian cancer.

PMID- 17013902
TI  - Holmes tremor: Application of modern neuroimaging techniques.
AB  - Holmes tremor has a characteristic rest, intention, and postural component. The
      syndrome arises as a consequence of a lesion in the upper brainstem and cerebral
      peduncles, which, it is postulated, interrupts the cerebello-rubrothalamic
      pathway. Ataxia, ophthalmoplegia, and bradykinesia are associated features. We
      present a case of Holmes tremor secondary to a midbrain cavernoma. Modern
      neuroimaging techniques in this case confirm that a combination of damage to the
      cerebello-rubrothalamic pathway and the nigrostriatal pathway is required for the
      full Holmes tremor syndrome to occur.

PMID- 17013903
TI  - Response to steroid treatment in anti-glutamic acid decarboxylase antibody
      associated cerebellar ataxia, stiff person syndrome and polyendocrinopathy.

PMID- 17013904
TI  - Phenotypic spectrum of PINK1-associated parkinsonism in 15 mutation carriers from
      1 family.
AB  - The phenotypic spectrum of PINK1-associated Parkinsonism was studied in a family
      with homozygous (n = 4) or heterozygous (n = 3) PINK1 mutations. All homozygous
      mutation carriers were definitely affected; the heterozygous carriers were
      asymptomatic but displayed unequivocal signs of probable or possible
      Parkinsonism. This finding suggests a role not only of homozygous but also of
      heterozygous PINK1 mutations in the development of parkinsonian signs and
      underlines the necessity to carefully investigate family members of affected
      mutation carriers.

PMID- 17013905
TI  - Neuropsychological profile of DYT1 dystonia.
AB  - The common belief that primary dystonia is a purely motor disorder has recently
      been challenged. We examined separately the cognitive profiles of symptomatic
      (SYM) and nonsymptomatic (N-SYM) groups of carriers of DYT1 mutation using a
      comprehensive neuropsychological test battery. Self-report inventories of
      anxiety, depression, and pain levels were also administered, as well as manual
      motor dexterity assessment. Each group was matched with healthy controls by age,
      sex, mother tongue, and education. No significant differences between the SYM
      group to its control group were found on cognitive tests evaluating verbal and
      nonverbal abstract abilities, attention, information processing speed, and
      spatial organization. However, the SYM group showed increased verbal memory
      retroactive interference. Interestingly, the patients also showed higher semantic
      fluency performance. No significant differences between the N-SYM group to
      controls were found. It was concluded that symptomatic DYT1 mutation carriers do
      not suffer the distinctive cognitive decline that is seen in other primary
      degenerative extrapyramidal disorders.

PMID- 17013907
TI  - Problematic gambling on dopamine agonists: Not such a rarity.
AB  - Excessive gambling is recognized with dopamine agonist therapy, but the
      prevalence is unknown. We assessed the prevalence of excess gambling by specific
      prospective enquiry in Parkinson's disease patients attending six West Scotland
      movement disorder clinics. Of 388 patients taking anti-Parkinson medication, 17
      (4.4%) developed pathological gambling, all of whom were prescribed dopamine
      agonists. Thus, 8% of patients taking dopamine agonists had pathological
      gambling. Pathological gambling is not uncommon, and patients should be made
      aware of this potential adverse effect.

PMID- 17013906
TI  - Open-label flexible-dose pilot study to evaluate the safety and tolerability of
      aripiprazole in patients with psychosis associated with Parkinson's disease.
AB  - Psychosis affects at least 5% to 8% of medication-treated patients with
      idiopathic Parkinson's disease (PD). Treatment options include reducing
      medications used for the treatment of PD-related motor symptoms or introducing an
      atypical antipsychotic drug. Only clozapine has been demonstrated to be
      efficacious and tolerated in double-blind controlled trials. This study evaluated
      the effect of aripiprazole, an atypical antipsychotic, on psychosis in PD in an
      open-label pilot study. Fourteen patients meeting entry criteria were started on
      aripiprazole 1 mg/day and titrated up to a maximum dose of 5 mg as needed.
      Subjects were evaluated on the Unified Parkinson's Disease Rating Scale (UPDRS)
      part III for motor function, the Neuropsychiatric Inventory (NPI), and the Brief
      Psychiatric Rating Scale (BPRS) for psychiatric response. Statistically
      significant improvement in mean BPRS and positive BPRS subscales occurred with
      open-label aripiprazole, but eight subjects discontinued the study due to
      worsened Parkinsonism (three), worsened psychosis (two), worsening of both (two),
      and lack of efficacy (one). While some patients had a favorable response,
      aripiprazole was associated with an exacerbation of motor symptoms. In this small
      study on psychosis in PD, aripiprazole did not appear promising.

PMID- 17013908
TI  - Novel mutation in the ceruloplasmin gene causing a cognitive and movement
      disorder with diabetes mellitus.
AB  - In a Chinese woman who had diabetes mellitus, undetectable ceruloplasmin, hand
      tremor, neck dystonia, and cognitive disturbances, genetic analyses revealed a
      novel homozygous mutation (848G > C or W283S) in exon 5 in the ceruloplasmin
      gene. Another member with a milder phenotype was also affected by this mutation.
      The healthy sister was heterozygous at the same position. Aceruloplasminemia has
      not yet been reported in China. This case suggests that increased awareness
      should be paid to this disorder in the presence of the typical symptoms.

PMID- 17013909
TI  - Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the
      differential diagnosis of Parkinsonian syndromes.
AB  - We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage
      biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of
      parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n =
      22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP;
      n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n =
      45) were included. CSF levels of NfH(SMI35) were measured using ELISA. Levels of
      CSF NfH(SMI35) were elevated in PSP compared to PD and controls (P < 0.05 each).
      They were also significantly higher in MSA than in PD and controls (P < 0.05
      each). NfH(SMI35) differentiated PD from PSP with a sensitivity of 76.5% and a
      specificity of 94.4%. Axonal damage as measured by CSF NfH(SMI35) is most
      prominent in the more rapidly progressive syndromes PSP and MSA as compared to PD
      or CBD. CSF NfH(SMI35) may therefore be of some value for the laboratory
      supported differential diagnosis of atypical parkinsonian syndromes.

PMID- 17013910
TI  - Parkinsonism due to lamotrigine.

PMID- 17013911
TI  - Effect of a concurrent task on driving performance in people with Parkinson's
      disease.
AB  - Numerous studies previously have reported reduced driving performance in people
      with Parkinson's disease (PD). Few studies to date, however, have examined how
      specific cognitive difficulties associated with PD impact on specific aspects of
      driving performance in this population. In this study, the impact of a concurrent
      task on driving performance was examined. A simulator was used to measure the
      driving behavior of 18 current drivers with PD and 18 matched controls. The
      presence of a concurrent task was manipulated between conditions. Results showed
      that, although groups were similarly affected by the concurrent task on most
      driving measures, participants with PD were disproportionately affected on
      operational level driving behavior. It also appears that participants with PD
      sacrificed concurrent task performance to maintain driving performance. These
      results further support the hypothesis that cognitive difficulties associated
      with PD compromise driving performance in this population, even in the mild to
      moderate stages of the disease.

PMID- 17013912
TI  - Expression of TrkB in the murine kidney.
AB  - Neurotrophins acting through Trk signal-transducing receptors play essential
      roles in the nervous system, and probably in some nonneuronal tissues. In the
      present study we used Western-blot and immunohistochemistry to investigate the
      occurrence and cellular localization of TrkB in the mouse kidney. Furthermore,
      the structure and ultrastructure of the kidney in mice carrying a mutation in the
      trkB gene were analyzed. TrkB in the kidney was identical to the cerebral one
      (145 kDa). Since the antibody used recognize a sequence within the tyrosine
      kinase domain of TrkB, the renal TrkB receptor identified here must be regarded
      as able to mediate biological effects of their ligands. TrkB immunoreactivity was
      restricted to the juxtaglomerular apparatus, including differentiated vascular
      cells and extaglomerular mesangial cells. In these cells, TrkB colocalized with
      renin. The structural analysis revealed no major changes in the kidney structure
      of TrkB-deficient mice, with the exception of a significant reduction of the
      glomerular area. Nevertheless, in these animals there was an apparent increase in
      the number of extraglomerular mesangial cells (which retain the ability to
      synthesize renin) and absence of the macula densa. Taken together, these results
      strongly suggest a role of TrkB and their ligands in the control of the normal
      development and maintenance of the juxtaglomerular apparatus.

PMID- 17013913
TI  - Cytotoxicity and fibroblast properties during in vitro test of biphasic calcium
      phosphate/poly-dl-lactide-co-glycolide biocomposites and different phosphate
      materials.
AB  - Reconstruction of bone defects is one of the major therapeutic goals in various
      clinical fields. Bone replacement materials must satisfy a number of criteria.
      Biological criteria are biocompatibility, controlled biodegradability, and
      osteoconductive or even osteogenic potential. The material should have a three
      dimensional structure with an interconnected pore system so as to permit cell
      growth and transport of substances. The surface must permit cell adhesion and
      proliferation. Composite biomaterials have enormous potential for natural bone
      tissue reparation, filling and augmentation. Calcium hydroxyapatite/polymer
      composite biomaterials belong to this group of composites and, because of their
      osteoconductive and biocompatible properties, can be successfully implemented
      within bone tissue reparations. In this study, possible differences between
      BCP/DLPLG, pure BCP, and Bio-Oss materials were examined in vitro. During
      overnight incubations, fibroblast and fibroblast-like cells (L929, MRC5) were
      able to adhere, spread, and remain viable on BCP, BCP/PLGA, and Bio-Oss discs, as
      was evidenced by using light- and LVSEM-microscopy. Inhibiting influence over the
      cell growth is more pronounced in the cases of BCP usage on both cell lines-
      41.29% for L929 and 43.08% for MRC-5 cells. MRC-5 cells are, within the given
      experimental conditions, less sensitive on inhibiting effects for the materials
      BCP/PLGA and Bio-Oss (10.13% and 10.76%, respectively) than for the L929 cell
      lines (23.02% and 15.44%, respectively).

PMID- 17013914
TI  - Long-term quality of life among Dutch prostate cancer survivors: results of a
      population-based study.
AB  - BACKGROUND: In this report, the authors describe the health-related quality of
      life (HRQL) of long-term prostate cancer survivors 5 to 10 years after diagnosis
      and compare it with the HRQL of an age-matched, normative sample of the general
      Dutch population. METHODS: The population-based Eindhoven Cancer Registry was
      used to select all men who were diagnosed with prostate cancer from 1994 to 1998.
      Nine hundred sixty-four patients received questionnaires (the 36-item Short Form
      Health Survey [SF-36] and the Quality of Life-Cancer Survivors questionnaire),
      and 780 of 964 patients responded (81%). RESULTS: Unselected, long-term prostate
      cancer survivors reported comparable HRQL scores but worse General Health
      Perceptions and better Mental Health scores than an age-matched, normative
      population. Patients who underwent radical prostatectomy had the highest physical
      HRQL, followed by patients who received 'watchful waiting,' and patients who
      received radiotherapy. Patients who received hormone treatment, in general, had
      the lowest physical HRQL. CONCLUSIONS: The results of this study suggested that
      the long-term HRQL of prostate cancer survivors may vary significantly as a
      function of the type of primary treatment. Because baseline differences between
      treatment groups cannot be excluded as part of the explanation for these
      differences, the current findings need to be verified in longitudinal studies.

PMID- 17013915
TI  - Prevalence of tic disorder in two schools in the Basque country: Results and
      methodological caveats.
AB  - Different studies have shown that the prevalence of tic disorder is highly
      variable, depending on the methodology employed. The aim of this study was to
      determine the prevalence of tic disorder among children of two schools. The study
      was conducted in three successive steps: information to parents and teachers by
      way of speeches and projection of videotapes; anonymous fulfilling of an ad hoc
      questionnaire by teachers and parents and identification of children as "possible
      tic disorder" according to the questionnaire; and confirmation of the presence of
      tics by direct observation of children at school (20 minutes in each classroom).
      Eight hundred sixty-seven children were included. Age ranged from 4 to 16 years.
      Ninety percent of parents and 99% of teachers fulfilled the questionnaire.
      Seventy-one children had tics according to parents' and 50 according to teachers'
      opinion (both coincided in 23 cases). Fifty-seven cases were identified after
      direct observation in the classroom (prevalence of 6.5%). The vast majority of
      tics were mild in severity and duration. Prevalence obtained in this study was
      comparable with data reported in studies using a similar methodology, which is
      higher than results shown in early studies addressed with less rigid methodology.
      Most of identified cases were quite mild, not leading to major functional
      disability. In spite of the methodology employed, it is possible that some cases
      were lost.

PMID- 17013917
TI  - Abstracts of the 20th Annual North American Cystic Fibrosis Conference, November
      2-5, 2006, Denver, Colorado, USA.

PMID- 17013916
TI  - Punding and dyskinesias.
AB  - The presence of punding in Parkinson's disease (PD) has been associated with
      inappropriate excessive use of dopaminergic medication but its relation to the
      severity of dyskinesias is not known. Through the use of clinical examination and
      medical chart review, the presence of punding and the severity of interdose
      dyskinesias were evaluated by two different observers. Punding was associated
      with more frequent interventions to reduce dyskinesias and with greater
      dyskinesia severity. We suggest the neural systems mediating the expression of
      dyskinesias and punding might overlap and that punding should be looked for
      systematically in PD patients presenting with disabling severe dyskinesias.

PMID- 17013920
TI  - Progressive motor syndrome in a welder with pallidal T1 hyperintensity on MRI: A
      two-year follow-up.
AB  - Chronic exposure to manganese (Mn) fume during welding may lead to mainly
      extrapyramidal syndrome that is resistant to treatment. We present a 32-year-old
      patient who developed severe postural instability, Parkinsonism, dystonia, and
      pyramidal signs in the 10th year of welding. The neurological condition of the
      patient worsened markedly in the following 3 years, resulting in severe
      disability rendering him to be assisted in all his daily activities and he did
      not benefit from any dopaminergic agent. T1 sequences of the MRI of the brain
      showed pallidal hyperintensity symmetrically. Welders in our country often
      protect their eyes but ignore to use tools that protect them from inhalation of
      the fume. Since chronic Mn toxicity may cause serious disability and irreversible
      neurological disturbances, we strongly believe that it is necessary to inform
      welders and their employers about this potential hazard.

PMID- 17013922
TI  - Early piribedil monotherapy of Parkinson's disease: A planned seven-month report
      of the REGAIN study.
AB  - Piribedil is a D2 dopamine agonist, which has been shown to improve symptoms of
      Parkinson's disease (PD) when combined with L-dopa. The objective of this study
      was to compare the efficacy of piribedil monotherapy to placebo in patients with
      early PD over a 7-month period. Four hundred and five early PD patients were
      randomized (double-blind) to piribedil (150-300 mg/day) or placebo. L-dopa open
      label supplementation was permitted. Unified Parkinson Disease Rating Scale part
      III (UPDRS III) score as the last observation on monotherapy over 7 months was
      the primary outcome measure. Secondary outcomes were proportion of responders
      (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months,
      UPDRS III subscores, and UPDRS II. UPDRS III improved on piribedil (-4.9 points)
      versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% CI
      = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher
      for piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P <
      0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II
      improved on piribedil by -1.2 points, while it deteriorated by 1.5 points on
      placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion
      of patients remaining on monotherapy after 7 months was greater in the piribedil
      group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that
      reported for other dopamine agonists, gastrointestinal side effects being the
      most common (22% of patients in piribedil group vs. 14% on placebo). Piribedil is
      effective and safe as early PD therapy.

PMID- 17013923
TI  - Olfactory imprinting is correlated with changes in gene expression in the
      olfactory epithelia of the zebrafish.
AB  - Odors experienced as juveniles can have significant effects on the behavior of
      mature organisms. A dramatic example of this occurs in salmon, where the odors
      experienced by developing fish determine the river to which they return as
      adults. Further examples of olfactory memories are found in many animals
      including vertebrates and invertebrates. Yet, the cellular and molecular bases
      underlying the formation of olfactory memory are poorly understood. We have
      devised a series of experiments to determine whether zebrafish can form olfactory
      memories much like those observed in salmonids. Here we show for the first time
      that zebrafish form and retain olfactory memories of an artificial odorant,
      phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate
      that exposure to PEA results in changes in gene expression within the olfactory
      sensory system. These changes are evident by in situ hybridization in the
      olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in
      situ hybridization demonstrates that the transcription factor, otx2, is up
      regulated in the olfactory sensory epithelia in response to PEA. This increase is
      evident at 2-3 days postfertilization and is maintained in the adult animals. We
      propose that the changes in otx2 gene expression are manifest as an increase in
      the number of neuronal precursors in the cells olfactory epithelium of the odor
      exposed fish. Thus, our results reveal a role for the environment in controlling
      gene expression in the developing peripheral nervous system.

PMID- 17013924
TI  - Microarray analysis of the developing cortex.
AB  - Abnormal development of the prefrontal cortex (PFC) is associated with a number
      of neuropsychiatric disorders that have an onset in childhood or adolescence.
      Although the basic laminar structure of the PFC is established in utero,
      extensive remodeling continues into adolescence. To map the overall pattern of
      changes in cortical gene transcripts during postnatal development, we made serial
      measurements of mRNA levels in mouse PFC using oligonucleotide microarrays. We
      observed changes in mRNA transcripts consistent with known postnatal
      morphological and biochemical events. Overall, most transcripts that changed
      significantly showed a progressive decrease in abundance after birth, with the
      majority of change between postnatal weeks 2 and 4. Genes with cell
      proliferative, cytoskeletal, extracellular matrix, plasma membrane
      lipid/transport, protein folding, and regulatory functions had decreases in mRNA
      levels. Quantitative PCR verified the microarray results for six selected genes:
      DNA methyltransferase 3A (Dnmt3a), procollagen, type III, alpha 1 (Col3a1),
      solute carrier family 16 (monocarboxylic acid transporters), member 1 (Slc16a1),
      MARCKS-like 1 (Marcksl1), nidogen 1 (Nid1) and 3-hydroxybutyrate dehydrogenase
      (heart, mitochondrial) (Bdh).

PMID- 17013925
TI  - Sex differences in the level of Bcl-2 family proteins and caspase-3 activation in
      the sexually dimorphic nuclei of the preoptic area in postnatal rats.
AB  - In developing rats, sex differences in the number of apoptotic cells are found in
      the central division of the medial preoptic nucleus (MPNc), which is a
      significant component of the sexually dimorphic nucleus of the preoptic area, and
      in the anteroventral periventricular nucleus (AVPV). Specifically, male rats have
      more apoptotic cells in the developing AVPV, whereas females have more apoptotic
      cells in the developing MPNc. To determine the mechanisms for the sex differences
      in apoptosis in these nuclei, we compared the expression of the Bcl-2 family
      members and active caspase-3 in postnatal female and male rats. Western blot
      analyses for the Bcl-2 family proteins were performed using preoptic tissues
      isolated from the brain on postnatal day (PD) 1 (day of birth) or on PD8. In the
      AVPV-containing tissues of PD1 rats, there were significant sex differences in
      the level of Bcl-2 (female > male) and Bax (female < male) proteins, but not of
      Bcl-xL or Bad proteins. In the MPNc-containing tissues of PD8 rats, there were
      significant sex differences in the protein levels for Bcl-2 (female < male), Bax
      (female > male), and Bad (female < male), but not for Bcl-xL. Immunohistochemical
      analyses showed significant sex differences in the number of active caspase-3
      immunoreactive cells in the AVPV on PD1 (female < male) and in the MPNc on PD8
      (female > male). We further found that active caspase-3-immunoreactive cells of
      the AVPV and MPNc were immunoreactive for NeuN, a neuronal marker. These results
      suggest that there are sex differences in the induction of apoptosis via the
      mitochondrial pathway during development of the AVPV and MPNc.

PMID- 17013926
TI  - Gender-dependent regulation of G-protein-gated inwardly rectifying potassium
      current in dorsal raphe neurons in knock-out mice devoid of the 5
      hydroxytryptamine transporter.
AB  - Agonists at G-protein-coupled receptors in neurons of the dorsal raphe nucleus
      (DRN) of knock-out mice devoid of the serotonin transporter (5-HTT(-/-)) exhibit
      lower efficacy to inhibit cellular discharge than in wild-type counterparts.
      Using patch-clamp whole-cell recordings, we found that a G-protein-gated inwardly
      rectifying potassium (GIRK) current is involved in the inhibition of spike
      discharge induced by 5-HT1A agonists (5-carboxamidotryptamine (5-CT) and (+/-)-2
      dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT);
      50 nM-30 microM) in both wild-type and 5-HTT(-/-) female and male mice. These
      effects were mimicked by 5'-guanylyl-imido-diphosphate (Gpp(NH)p; 400 microM)
      dialysis into cells with differences between genders. The 5-HTT(-/-) knock-out
      mutation reduced the current density induced by Gpp(NH)p in females but not in
      males. These data suggest that the decreased response of 5-HT1A receptors to
      agonists in 5-HTT(-/-) mutants reflects notably alteration in the coupling
      between G-proteins and GIRK channels in females but not in males. Accordingly,
      gender differences in central 5-HT neurotransmission appear to depend-at least in
      part-on sex-related variations in corresponding receptor-G protein signaling
      mechanisms.

PMID- 17013927
TI  - LAR protein tyrosine phosphatase receptor associates with TrkB and modulates
      neurotrophic signaling pathways.
AB  - The identities of receptor protein tyrosine phosphatases (PTPs) that associate
      with Trk protein tyrosine kinase (PTK) receptors and modulate neurotrophic
      signaling are unknown. The leukocyte common antigen-related (LAR) receptor PTP is
      present in neurons expressing TrkB, and like TrkB is associated with caveolae and
      regulates survival and neurite outgrowth. We tested the hypothesis that LAR
      associates with TrkB and regulates neurotrophic signaling in embryonic
      hippocampal neurons. Coimmunoprecipitation and coimmunostaining demonstrated LAR
      interaction with TrkB that is increased by BDNF exposure. BDNF neurotrophic
      activity was reduced in LAR-/- and LAR siRNA-treated LAR+/+ neurons and was
      augmented in LAR-transfected neurons. In LAR-/- neurons, BDNF-induced activation
      of TrkB, Shc, AKT, ERK, and CREB was significantly decreased; while in LAR
      transfected neurons, BDNF-induced CREB activation was augmented. Similarly,
      LAR+/+ neurons treated with LAR siRNA demonstrated decreased activation of Trk
      and AKT. LAR is known to activate the Src PTK by dephosphorylation of its
      negative regulatory domain and Src transactivates Trk. In LAR-/- neurons, or
      neurons treated with LAR siRNA, phosphorylation of the Src regulatory domain was
      increased (indicating Src inactivation), consistent with a role for Src in
      mediating LAR's ability to up-regulate neurotrophic signaling. Interactions
      between LAR, TrkB, and Src were further confirmed by the findings that Src
      coimmunoprecipitated with LAR, that the Src inhibitor PP2 blocked the ability of
      LAR to augment TrkB signaling, and that siRNA-induced depletion of Src decreased
      LAR interaction with TrkB. These studies demonstrate that receptor PTPs can
      associate with Trk complexes and promote neurotrophic signaling and point to
      receptor PTP-based strategies as a novel approach for modulating neurotrophin
      function.

PMID- 17013928
TI  - Brain-derived neurotrophic factor selectively regulates dendritogenesis of
      parvalbumin-containing interneurons in the main olfactory bulb through the
      PLCgamma pathway.
AB  - Molecular mechanisms of neurotrophin signaling on dendrite development and
      dynamics are only partly understood. To address the role of brain-derived
      neurotrophic factor (BDNF) in the morphogenesis of GABAergic neurons of the main
      olfactory bulb, we analyzed mice lacking BDNF, mice carrying neurotrophin-3 (NT3)
      in the place of BDNF, and TrkB signaling mutant mice with a receptor that can
      activate phospholipase Cgamma (PLCgamma) but is unable to recruit the adaptors
      Shc/Frs2. BDNF deletion yielded a compressed olfactory bulb with a significant
      loss of parvalbumin (PV) immunoreactivity in GABAergic interneurons of the
      external plexiform layer. Dendrite development of PV-positive interneurons was
      selectively attenuated by BDNF since other Ca2+ -binding protein-containing
      neuron populations appeared unaffected. The deficit in PV-positive neurons could
      be rescued by the NT3/NT3 alleles. The degree of PV immunoreactivity was
      dependent on BDNF and TrkB recruitment of the adaptor proteins Shc/Frs2. In
      contrast, PLCgamma signaling from the TrkB receptor was sufficient for dendrite
      growth in vivo and consistently, blocking PLCgamma prevented BDNF-dependent
      dendrite development in vitro. Collectively, our results provide genetic evidence
      that BDNF and TrkB signaling selectively regulate PV expression and dendrite
      growth in a subset of neurochemically-defined GABAergic interneurons via
      activation of the PLCgamma pathway.

PMID- 17013929
TI  - On the trigeminal percept of androstenone and its implications on the rate of
      specific anosmia.
AB  - Specific anosmia is a term that describes an inability to perceive a particular
      odorant in the context of an otherwise normal olfactory acuity. The most common
      example, for the odor of androstenone, has been ascribed a prevalence ranging
      from 2 to 45%. In two experiments we sought to determine whether this wide range
      could be explained by the difference in steroid concentrations used, and by the
      degree to which the trigeminal system contributes to perception of androstenone.
      Experiment 1 demonstrated that high concentrations of androstenone stimulated the
      trigeminal system, as indicated by electrophysiological recordings. Experiment 2
      demonstrated that conscious detection of androstenone is possible based solely on
      the trigeminal system. Interestingly, detection seems to interact with olfactory
      acuity in that subjects with a low olfactory sensitivity to androstenone were
      better able to detect its trigeminal component. The agreement between conscious
      experience and behavioral discrimination was not well calibrated, in that
      subjects demonstrated a clear overconfidence in their abilities. Altogether, the
      current study suggests that androstenone is an odorant that produces a
      concentration-dependent degree of trigeminal stimulation. This trigeminal
      component explains the diversity of the reported prevalence of specific anosmia
      for androstenone and might have implications on future use of specific anosmia as
      a tool to understand odor processing.

PMID- 17013930
TI  - ERK/MAPK pathway regulates GABAA receptors.
AB  - The GABAA receptor is a ligand-gated ion channel whose function and activity can
      be regulated by ligand binding or alternatively may be influenced indirectly
      through the phosphorylation of specific subunits that comprise the GABAA receptor
      pentamer. With respect to phosphorylation, most studies have focused on either
      beta or gamma subunits, whereas the role of the alpha subunit as a relevant
      target of signaling kinases is largely unknown. Interestingly, we found a
      putative phosphorylation site for extracellular-signal regulated kinase (ERK), a
      key effector of the MAPK pathway, in almost all known alpha subunits of the GABAA
      receptor, including the ubiquitously expressed alpha1 subunit. To determine
      whether this putative ERK phosphorylation site was functionally relevant, we
      evaluated if ERK inhibition (through pharmacological inhibition of its upstream
      kinase, MEK) altered GABA-gated currents. Using HEK293 cells stably transfected
      with the alpha1beta2gamma2 form of the GABAA receptor, we found that UO126
      reduced basal ERK phosphorylation and resulted in an enhancement of GABA-induced
      peak current amplitudes. Further, the enhancement of GABA-gated currents required
      an intact intracellular environment as it was robust in perforated patch
      recordings (which preserves the intracellular milieu), but absent in conventional
      whole-cell recordings (which dialyzes the cytosolic contents), supporting the
      involvement of an intracellular signaling pathway. Finally, mutation of the ERK
      phosphorylation site (T375-->A) prevented the UO126-induced enhancement of GABA
      gated currents. Collectively, our results implicate the MAPK pathway as a
      negative modulator of GABAA receptor function, whose influence on GABA-gated
      currents may be mediated by phosphorylation of the alpha subunit.

PMID- 17013932
TI  - Glycosylation of an immunoglobulin produced from a murine hybridoma cell line:
      the effect of culture mode and the anti-apoptotic gene, bcl-2.
AB  - The impact of bcl-2 over-expression on the glycosylation pattern of an antibody
      produced by a bcl-2 transfected hybridoma cell line (TB/C3.bcl-2) was
      investigated in suspension batch, continuous and high cell density culture (Flat
      hollow fibre, Tecnomouse system). In all culture modes bcl-2 over-expression
      resulted in higher cell viability. Analysis of the glycans from the IgG of batch
      cultures showed that >95% of the structures were neutral core fucosylated asialo
      biantennary oligosaccharides with variable terminal galactosylation (G0f, G1f and
      G2f) consistent with previous analysis of glycans from the conserved site at Asn
      297 of the IgG protein. The galactosylation index (GI) was determined as an
      indicator of the glycan profile (=(G2 + 0.5* G1)/(G0 + G1 + G2)). GI values in
      control cultures were comparable to bcl-2 cultures during exponential growth
      (0.53) but declined toward the end of the culture when there was a loss in cell
      viability. Low dilution rates in chemostat culture were associated with reduced
      galactosylation of the IgG glycans in both cell lines. However, at the higher
      dilution rates the GI for IgG was consistently higher in the TB/C3.bcl-2
      cultures. In the hollow fibre bioreactor the galactosylation of the IgG glycans
      was considerably lower than in suspension batch or continuous cultures with GI
      values averaging 0.38. Similar low galactosylation values have been found
      previously for high density cell cultures and these are consistent with the low
      values obtained when the dissolved oxygen level is maintained at a low value
      (10%) in controlled suspension cultures of hybridomas.

PMID- 17013931
TI  - Engraftment and differentiation of embryonic stem cell-derived neural progenitor
      cells in the cochlear nerve trunk: growth of processes into the organ of Corti.
AB  - Hearing loss in mammals is irreversible because cochlear neurons and hair cells
      do not regenerate. To determine whether we could replace neurons lost to primary
      neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived
      mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed
      animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while
      leaving hair cells intact by ouabain application to the round window at the base
      of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen
      that expressed endogenous EYFP and could be immunolabeled for neuron-specific
      markers. Twelve days after transplantation, the grafts had neurons that extended
      processes from the nerve core toward the denervated organ of Corti. By 64-98
      days, the grafts had sent out abundant processes that occupied a significant
      portion of the space formerly occupied by the cochlear nerve. The neurites grew
      in fasciculating bundles projecting through Rosenthal's canal, the former site of
      spiral ganglion cells, into the osseous spiral lamina and ultimately into the
      organ of Corti, where they contacted hair cells. Neuronal counts showed a
      significant increase in neuronal processes near the sensory epithelium, compared
      to animals that were denervated without subsequent stem cell transplantation. The
      regeneration of these neurons shows that neurons differentiated from stem cells
      have the capacity to grow to a specific target in an animal model of neuronal
      degeneration.

PMID- 17013933
TI  - The Si-tag for immobilizing proteins on a silica surface.
AB  - Targeting functional proteins to specific sites on a silicon device is essential
      for the development of new biosensors and supramolecular assemblies. Using
      intracellular lysates of several bacterial strains, we found that ribosomal
      protein L2 binds tightly to silicon particles, which have surfaces that are
      oxidized to silica. A fusion of E. coli L2 and green fluorescence protein
      adsorbed to the silica particles with a K(d) of 0.7 nM at pH 7.5 and also
      adsorbed to glass slides. This fusion protein was retained on the glass slide
      even after washing for 24 h with a buffer containing 1 M NaCl. We mapped the
      silica-binding domains of E. coli L2 to amino acids 1-60 and 203-273. These two
      regions seemed to cooperatively mediate the strong silica-binding characteristics
      of L2. A fusion of L2 and firefly luciferase also adsorbed on the glass slide.
      This L2 silica-binding tag, which we call the "Si-tag," can be used for one-step
      targeting of functional proteins on silica surfaces.

PMID- 17013934
TI  - Bio-reductive dechlorination of 1,1,1-trichloroethane and chloroform using a
      hydrogen-based membrane biofilm reactor.
AB  - A H(2)-based, denitrifying and sulfate-reducing membrane biofilm reactor (MBfR)
      was effective for removing 1,1,1-trichloroethane (TCA) and chloroform (CF) by
      reductive dechlorination. When either TCA or CF was first added to the MBfR,
      reductive dechlorination took place immediately and then increased over 3 weeks,
      suggesting enrichment for TCA- or CF-dechlorinating bacteria. Increasing the H(2)
      pressure increased the dechlorination rates of TCA or CF, and it also increased
      the rate of sulfate reduction. Increased sulfate loading allowed more sulfate
      reduction, and this competed with reductive dechlorination, particularly the
      second steps. The acceptor flux normalized by effluent concentration can be an
      efficient indicator to gauge the intrinsic kinetics of the MBfR biofilms for the
      different reduction reactions. The analysis of normalized rates showed that the
      kinetics for reductive-dechlorination reactions were slowed by reduced H(2) bio
      availability caused by a low H(2) pressure or competition from sulfate reduction.

PMID- 17013935
TI  - Redox-stratification controlled biofilm (ReSCoBi) for completely autotrophic
      nitrogen removal: the effect of co- versus counter-diffusion on reactor
      performance.
AB  - A multi-population biofilm model for completely autotrophic nitrogen removal was
      developed and implemented in the simulation program AQUASIM to corroborate the
      concept of a redox-stratification controlled biofilm (ReSCoBi). The model
      considers both counter- and co-diffusion biofilm geometries. In the counter
      diffusion biofilm, oxygen is supplied through a gas-permeable membrane that
      supports the biofilm while ammonia (NH(4)(+)) is supplied from the bulk liquid.
      On the contrary, in the co-diffusion biofilm, both oxygen and NH(4)(+) are
      supplied from the bulk liquid. Results of the model revealed a clear
      stratification of microbial activities in both of the biofilms, the resulting
      chemical profiles, and the obvious effect of the relative surface loadings of
      oxygen and NH(4)(+) (J(O(2))/J(NH(4)(+))) on the reactor performances. Steady
      state biofilm thickness had a significant but different effect on T-N removal for
      co- and counter-diffusion biofilms: the removal efficiency in the counter
      diffusion biofilm geometry was superior to that in the co-diffusion counterpart,
      within the range of 450-1,400 microm; however, the efficiency deteriorated with a
      further increase in biofilm thickness, probably because of diffusion limitation
      of NH(4)(+). Under conditions of oxygen excess (J(O(2))/J(NH(4)(+)) > 3.98),
      almost all NH(4)(+) was consumed by aerobic ammonia oxidation in the co-diffusion
      biofilm, leading to poor performance, while in the counter-diffusion biofilm, T-N
      removal efficiency was maintained because of the physical location of anaerobic
      ammonium oxidizers near the bulk liquid. These results clearly reveal that
      counter-diffusion biofilms have a wider application range for autotrophic T-N
      removal than co-diffusion biofilms.

PMID- 17013936
TI  - Stability and catalytic activity of alpha-amylase from barley malt at different
      pressure-temperature conditions.
AB  - The impact of high hydrostatic pressure and temperature on the stability and
      catalytic activity of alpha-amylase from barley malt has been investigated.
      Inactivation experiments with alpha-amylase in the presence and absence of
      calcium ions have been carried out under combined pressure-temperature treatments
      in the range of 0.1-800 MPa and 30-75 degrees C. A stabilizing effect of Ca(2+)
      ions on the enzyme was found at all pressure-temperature combinations
      investigated. Kinetic analysis showed deviations of simple first-order reactions
      which were attributed to the presence of isoenzyme fractions. Polynomial models
      were used to describe the pressure-temperature dependence of the inactivation
      rate constants. Derived from that, pressure-temperature isokinetic diagrams were
      constructed, indicating synergistic and antagonistic effects of pressure and
      temperature on the inactivation of alpha-amylase. Pressure up to 200 MPa
      significantly stabilized the enzyme against temperature-induced inactivation. On
      the other hand, pressure also hampers the catalytic activity of alpha-amylase and
      a progressive deceleration of the conversion rate was detected at all
      temperatures investigated. However, for the overall reaction of blocked p
      nitrophenyl maltoheptaoside cleavage and simultaneous occurring enzyme
      inactivation in ACES buffer (0.1 M, pH 5.6, 3.8 mM CaCl(2)), a maximum of
      substrate cleavage was identified at 152 MPa and 64 degrees C, yielding
      approximately 25% higher substrate conversion after 30 min, as compared to the
      maximum at ambient pressure and 59 degrees C.

PMID- 17013937
TI  - Detection of S100 protein from prostatic cancer patients using anti-S100 protein
      antibody immobilized on POS-PVA discs.
AB  - The S100 proteins have been extensively used as cancer biomarkers. The objectives
      of the present work were to immobilize the antibody anti-protein S100 to a net of
      semi-interpenetrated of polysiloxane and polyvinyl alcohol (POS-PVA discs), to
      investigate its capacity to capture S100 protein from serum and to quantify it by
      ELISA in sera from patients with prostatic adenocarcinoma (n = 15) and healthy
      individuals (n = 10). Also these values were compared to the S100 protein
      expression in the prostatic tissue through immunohistochemistry. The POS-PVA
      discs fixed about 92.8% of the offered antibody (7.75 microg of antibody per
      disc). The best values of the immobilized no-marked antibody anti-S100 and serum
      dilution were found to be 10 microg and 1:400, respectively. Optical density (OD)
      values for the sera of patients (0.425 +/- 0.042) with prostatic adenocarcinoma
      were significantly lower (P < 0.05) compared to those established for the healthy
      individuals (1.034 +/- 0.124). In the immunohistochemistry study no significant
      variations were observed in the number of positive S100 cells between prostatic
      adenocarcinoma (153.45 +/- 16.82) and normal prostate (147.04 +/- 18.98). These
      results showed a clear difference between S100 proteins expressed in tissue and
      presented in serum during the prostatic tissue neoplasic transformation. Sera
      analysis was more sensitive than immunohistochemistry S100 protein detection in
      the prostate tissue besides the advantage to be less invasive method.

PMID- 17013939
TI  - On maintenance models in severely and long-term limited membrane bioreactor
      cultivations.
AB  - Membrane bioreactors (MBRs) are combinations of common bioreactors and membrane
      separation units for biomass retention. Through increased biomass concentration,
      they allow increased productivity (or smaller reactor volume, respectively).
      Besides high biomass concentrations, operation at very low growth rates is
      typical for MBRs. In this regime, maintenance metabolism where substrate uptake
      only yields energy for cell survival becomes of higher importance than in
      processes run at higher growth rates. While thermodynamically based correlations
      for the prediction of maintenance coefficients are available for chemostat or
      other medium growth rate processes, some authors have mentioned a change in
      energy demand in MBRs and a dependence of maintenance parameters on operating
      conditions. Due to the fact that often mixed cultures are used and resulting from
      the different evaluation methods used by different authors, views on the possible
      influences on maintenance parameters differ. However, it is accepted that common
      models describing microbial growth and production of metabolites or degradation
      of pollutants do not consider the effects caused by severe limitations and
      therefore cannot sufficiently be applied to MBRs. In this study, maintenance
      parameters were determined for a model organism (Ustilago maydis) and results
      from different evaluation methods were compared. A continuous fit of respiration
      data gave more consistent results than the traditional method of plotting
      specific uptake versus growth rate. They suggest that below micro = 10%
      micro(max) the maintenance coefficient drops to a third of the value in short
      term limited cultures.

PMID- 17013940
TI  - MODEL-molecular descriptor lab: a web-based server for computing structural and
      physicochemical features of compounds.
AB  - Molecular descriptors represent structural and physicochemical features of
      compounds. They have been extensively used for developing statistical models,
      such as quantitative structure activity relationship (QSAR) and artificial neural
      networks (NN), for computer prediction of the pharmacodynamic, pharmacokinetic,
      or toxicological properties of compounds from their structure. While computer
      programs have been developed for computing molecular descriptors, there is a lack
      of a freely accessible one. We have developed a web-based server, MODEL
      (Molecular Descriptor Lab), for computing a comprehensive set of 3,778 molecular
      descriptors, which is significantly more than the approximately 1,600 molecular
      descriptors computed by other software. Our computational algorithms have been
      extensively tested and the computed molecular descriptors have been used in a
      number of published works of statistical models for predicting variety of
      pharmacodynamic, pharmacokinetic, and toxicological properties of compounds.
      Several testing studies on the computed molecular descriptors are discussed.
      MODEL is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/model/model.cgi free of
      charge for academic use.

PMID- 17013942
TI  - Modeling of local dynamic behavior of phenol degradation in an internal loop
      airlift bioreactor by yeast Candida tropicalis.
AB  - A coupled computational fluid dynamic (CFD) model, combining hydrodynamics with
      biochemical reactions, was developed to simulate the local transient flow
      patterns and the dynamic behaviors of cell growth and phenol biodegradation by
      yeast Candida tropicalis in an internal loop airlift reactor (ILALR). To validate
      this proposed model effectively, the simulated local hydrodynamic characteristics
      of the gas-mineral salt medium solution (gas-liquid) two-phase system, at a
      phenol concentration of 1,200 mg L(-1) and no presence of cells, was
      experimentally investigated in the ILALR using laser Doppler anemometer (LDA)
      measurements and conductivity probe. Furthermore, the validation of the simulated
      phenol biodegradation behavior by C. tropicalis at different initial
      concentrations of phenol and cell was also carried out in the ILALR. The time
      averaged and transient results of the model simulations illustrated a
      satisfactory agreement with the experimental data. Finally, the local
      instantaneous flow and phenol biodegradation features, including gas holdup, gas
      velocity, liquid velocity, cell concentration, and phenol concentration inside
      the ILALR were successfully predicted by the proposed model.

PMID- 17013941
TI  - Metabolic engineering of sesquiterpene metabolism in yeast.
AB  - Terpenes are structurally diverse compounds that are of interest because of their
      biological activities and industrial value. These compounds consist of chirally
      rich hydrocarbon backbones derived from terpene synthases, which are subsequently
      decorated with hydroxyl substituents catalyzed by terpene hydroxylases.
      Availability of these compounds is, however, limited by intractable synthetic
      means and because they are produced in low amounts and as complex mixtures by
      natural sources. We engineered yeast for sesquiterpene accumulation by
      introducing genetic modifications that enable the yeast to accumulate high levels
      of the key intermediate farnesyl diphosphate (FPP). Co-expression of terpene
      synthase genes diverted the enlarged FPP pool to greater than 80 mg/L of
      sesquiterpene. Efficient coupling of terpene production with hydroxylation was
      also demonstrated by coordinate expression of terpene hydroxylase activity,
      yielding 50 mg/L each of hydrocarbon and hydroxylated products. These yeast now
      provide a convenient format for investigating catalytic coupling between terpene
      synthases and hydroxylases, as well as a platform for the industrial production
      of high value, single-entity and stereochemically unique terpenes.

PMID- 17013943
TI  - Responses of the photosynthetic machinery of Spirulina maxima to induced reactive
      oxygen species.
AB  - The photosynthetic machinery of Spirulina maxima was studied when subjected to
      induced reactive oxygen species (ROS) to examine the organism's responses to
      stress. Significant decreases in both photosynthetic efficiency and growth rate
      were observed. Exposure to 0.01 mmol H(2)O(2)/(g cell), which induced the lowest
      specific intracellular ROS level (siROS) led to a 15% decrease in specific growth
      rate; an increase in siROS by 70-fold led to a 25% decrease in specific growth
      rate. Similarly, siROS induced by 0.01 mmol H(2)O(2)/(g cell) led to 15%
      inhibition in photosynthetic efficiency, while an increase in siROS by 40- or 70
      fold led to about 60% inhibition in photosynthetic efficiency. To further
      understand the effects of induced ROS on photosynthetic machinery, we performed a
      detailed pigmentation analysis as well as analyzed Phycobilisomes (PBS),
      Photosystem II (PSII), and Photosystem I (PSI), the three important components of
      cyanobacterial photosynthetic apparatus. We found carotenoids (beta-carotene and
      lutein) to be most sensitive to siROS. Also, specific levels of phycocyanin and
      allophycocyanin, which are important PBS pigments, decreased significantly in
      response to H(2)O(2). Further, electron transport assays revealed that ROS cause
      damage primarily to PSII, whereas they do not significantly affect PSI in
      comparison; siROS induced by 0.01 mmol H(2)O(2)/(g cell) led to a 15% inhibition
      of PSII, and increase in siROS by 9-, 40-, and 70-fold led to 22%, 36%, and 46%
      inhibition, respectively.

PMID- 17013944
TI  - The conformational quality of insoluble recombinant proteins is enhanced at low
      growth temperatures.
AB  - Protein aggregation is a major bottleneck during the bacterial production of
      recombinant proteins. In general, the induction of gene expression at sub-optimal
      growth temperatures improves the solubility of aggregation-prone polypeptides and
      minimizes inclusion body (IB) formation. However, the effect of low temperatures
      on the quality of the recombinant protein, especially within the insoluble cell
      fraction, has been hardly ever explored. In this work, we have examined the
      conformational status of a recombinant GFP protein when produced in Escherichia
      coli below 37 degrees C. As expected, the fraction of aggregated protein largely
      decreased at lower temperatures, while the conformational quality of both soluble
      and aggregated GFP, as reflected by its specific fluorescence emission,
      progressively improved. This observation indicates that physicochemical
      conditions governing protein folding affect concurrently the quality of the
      soluble and the aggregated forms of a misfolding-prone protein, and that protein
      misfolding and aggregation are clearly not coincident events.

PMID- 17013945
TI  - The YfiD protein contributes to the pyruvate formate-lyase flux in an Escherichia
      coli arcA mutant strain.
AB  - The product of yfiD gene is similar to pyruvate formate-lyase (PFL) activase and
      it has been reported to activate PFL by replacing the glycyl radical domain. To
      quantitate the effect of YfiD on the cell metabolism in microaerobic cultures,
      glucose-limited chemostat cultures were conducted with Escherichia coli yfiD
      mutant and yfiDarcA mutant strains. The microaerobic condition was controlled by
      purging the culture media with 2.5% O(2) in N(2). The intracellular metabolic
      flux distributions in these cultures were estimated based on C-13 labeling
      experiments. By comparing with the flux distributions in wild-type E. coli and
      the arcA mutant, it was shown that YfiD contributes to about 18% of the PFL flux
      in the arcA mutant, but it did not contribute to the PFL flux in wild-type E.
      coli. It was also shown that the cell used both PFL and pyruvate dehydrogenase
      (PDH) to supplement the acetyl-coenzyme A (AcCoA) pool under microaerobic
      conditions. The flux through PDH was about 22-30% of the total flux toward AcCoA
      in the wild-type, the yfiD mutant and yfiDarcA mutant strains. Relatively higher
      lactate production was seen in the yfiDarcA mutant than the other strains, which
      was due to the lower total flux through PFL and PDH toward AcCoA in this strain.

PMID- 17013946
TI  - Production of bio-hydrogen by mesophilic anaerobic fermentation in an acid-phase
      sequencing batch reactor.
AB  - The pH and hydraulic retention time (HRT) of an anaerobic sequencing batch
      reactor (ASBR) were varied to optimize the conversion of carbohydrate-rich
      synthetic wastewater into bio-hydrogen. A full factorial design using
      evolutionary operation (EVOP) was used to determine the effect of the factors and
      to find the optimum condition of each factor required for high hydrogen
      production rate. Experimental results from 20 runs indicate that a maximum
      hydrogen production rate of 4,460-5,540 mL/L/day under the volumetric organic
      loading rate (VOLR) of 75 g-COD/L/day obtained at an observed design point of HRT
      = 8 h and pH = 5.7. The hydrogen production rate was strongly dependent on the
      HRT, and the effect was statistically significant (P < 0.05). However, no
      significant effect (P > 0.05) was found for the pH on the hydrogen production
      rate. When the ASBR conditions were set for a maximum hydrogen production rate,
      the hydrogen production yield and specific hydrogen production rate were 60-74
      mL/g-COD and 330-360 mL/g-VSS/day, respectively. The hydrogen composition was 43
      51%, and no methanogenesis was observed. Acetate, propionate, butyrate, valerate,
      caproate, and ethanol were major liquid intermediate metabolites during runs of
      this ASBR. The dominant fermentative types were butyrate-acetate or ethanol
      acetate, representing the typical anaerobic pathway of Clostridium species. This
      hydrogen-producing ASBR had a higher hydrogen production rate, compared with that
      produced using continuous-flow stirred tank reactors (CSTRs). This study suggests
      that the hydrogen-producing ASBR is a promising bio-system for prolonged and
      stable hydrogen production.

PMID- 17013947
TI  - Effect of drug-test interactions on length of hospital stay.
AB  - PURPOSE: To evaluate the impact of drug-laboratory test interactions on the
      length of stay of hospitalised patients. METHODS: Observational study of 404
      discharges from the Internal Medicine Services of a tertiary hospital. Databases
      with information on general data, medication and tests performed were linked with
      the potential interactions described in the literature. This revealed the
      potential interactions between drugs and laboratory tests (PIDL) in each patient.
      Several linear regression models, adjusted for confounders, were performed to
      test the effect of both the number of PIDL and their influence on tests results
      (false positive/negative) on the length of stay. RESULTS: A total of 19 741 PIDL
      were detected; 5954 could give rise to potential false positive (PFP) results and
      8442 to potential false negative (PFN) ones. Each PFP was related to an increase
      of 0.051 days in stay duration (CI95% 0.001-0.102) and each PFN to 0.045 days
      (CI95% 0.008-0.081). Globally, 303 and 380 days of hospitalisation could be
      attributed to false positives and false negatives, which could account for 9.8%
      of the total stay of these patients. CONCLUSIONS: These results show that the
      interactions between drugs and laboratory tests produce a statistically and
      clinically significant increase in the duration of hospital stay.

PMID- 17013950
TI  - Fluorescent H-aggregates of merocyanine dyes.

PMID- 17013948
TI  - Decline of neuroadrenergic bronchial innervation and respiratory function in type
      1 diabetes mellitus: a longitudinal study.
AB  - BACKGROUND AND AIM: Type 1 diabetes mellitus complicated by autonomic neuropathy
      (AN) is characterized by depressed cholinergic bronchomotor tone and
      neuroadrenergic denervation of the lung. We explored the effects of AN on the
      rate of decline of pulmonary sympathetic innervation and respiratory function
      during a 5-year follow-up. METHODS: Twenty diabetic patients, 11 with AN, were
      enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated
      haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients
      underwent respiratory function tests and a ventilatory scintigraphic study of
      neuroadrenergic bronchial innervation using 123I-MIBG. RESULTS: During follow-up
      4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity
      (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed
      comparable rates of decrease in patients with and without AN. The yearly decline
      of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate,
      in both AN and AN-free patients. The MIBG clearance significantly increased both
      in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52
      min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/-
      13.52 min, respectively), indicating a rapidly progressive neuroadrenergic
      denervation. The rate of the neuroadrenergic denervation was inversely related to
      the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p =
      0.017). Neither respiratory function indexes nor MIBG clearance changes
      correlated with the overall HbA1c values. CONCLUSIONS: Neuroadrenergic
      denervation of the lung parallels the decline of respiratory function indexes in
      diabetic patients both with and without AN and seems to be independent from the
      quality of glycemic control.

PMID- 17013951
TI  - Hierarchical growth of large-scale ordered zeolite silicalite-1 membranes with
      high permeability and selectivity for recycling CO2.

PMID- 17013952
TI  - Oxetanes as promising modules in drug discovery.

PMID- 17013953
TI  - Synthesis of the C31-C67 fragment of amphidinol 3.

PMID- 17013954
TI  - Total synthesis of IKD-8344.

PMID- 17013955
TI  - A pathway for NH addition to styrene promoted by gold.

PMID- 17013956
TI  - Kinetic resolution of 4-hydroxy-2-ketones catalyzed by a Baeyer-Villiger
      monooxygenase.

PMID- 17013957
TI  - Formation and structure of a stable monoradical cation by reduction of a
      diphosphafulvenium salt.

PMID- 17013958
TI  - Dynamic motion of building blocks in porous coordination polymers.

PMID- 17013959
TI  - Layer-by-layer deposition of rhenium-containing hyperbranched polymers and
      fabrication of photovoltaic cells.
AB  - Multilayer thin films were prepared by the layer-by-layer (LBL) deposition method
      using a rhenium-containing hyperbranched polymer and poly[2-(3-thienyl)ethoxy-4
      butylsulfonate] (PTEBS). The radii of gyration of the hyperbranched polymer in
      solutions with different salt concentrations were measured by laser light
      scattering. A significant decrease in molecular size was observed when sodium
      trifluoromethanesulfonate was used as the electrolyte. The conditions of
      preparing the multilayer thin films by LBL deposition were studied. The growth of
      the multilayer films was monitored by absorption spectroscopy and spectroscopic
      ellipsometry, and the surface morphologies of the resulting films were studied by
      atomic force microscopy. When the pH of a PTEBS solution was kept at 6 and in the
      presence of salt, polymer films with maximum thickness were obtained. The
      multilayer films were also fabricated into photovoltaic cells and their
      photocurrent responses were measured upon irradiation with simulated air mass
      (AM) 1.5 solar light. The open-circuit voltage, short-circuit current, fill
      factor, and power conversion efficiency of the devices were 1.2 V, 27.1 mu A cm(
      2), 0.19, and 6.1x10(-3) %, respectively. The high open-circuit voltage was
      attributed to the difference in the HOMO level of the PTEBS donor and the LUMO
      level of the hyperbranched polymer acceptor. A plot of incident photon-to
      electron conversion efficiency versus wavelength also suggests that the
      PTEBS/hyperbranched polymer junction is involved in the photosensitization
      process, in which a maximum was observed at approximately 420 nm. The relatively
      high capacitance, determined from the measured photocurrent rise and decay
      profiles, can be attributed to the presence of large counter anions in the
      polymer film.

PMID- 17013960
TI  - Synthesis of (+/-)-strychnofoline via a highly convergent selective annulation
      reaction.
AB  - Studies aimed at preparing (+/-)-strychnofoline by total synthesis are detailed.
      The route described makes use of a recently developed MgI(2)-mediated ring
      expansion reaction of spiro[cyclopropan-1,3'-oxindole] with a cyclic
      disubstituted aldimine. The ring-expansion product was formed as a single
      diastereoisomer in 55 % yield, possessing the same stereochemical pattern found
      in strychnofoline. In addition, our synthetic effort has led to the development
      of new reaction methodology to access 3,4-disubstituted cyclic aldimines.

PMID- 17013961
TI  - Structures and vibrational spectra of the sulfur-rich oxides SnO (n = 4-9): the
      importance of pi*-pi* interactions.
AB  - The structures of a large number of isomers of the sulfur oxides S(n)O with n = 4
      9 have been calculated at the G3X(MP2) level of theory. In most cases, homocyclic
      molecules with exocyclic oxygen atoms in an axial position are the global minimum
      structures. Perfect agreement is obtained with experimentally determined
      structures of S(7)O and S(8)O. The most stable S(4)O isomer as well as some less
      stable isomers of S(5)O and S(6)O are characterized by a strong pi*-pi*
      interaction between S==O and S==S groups, which results in relatively long S--S
      bonds with internuclear distances of 244-262 pm. Heterocyclic isomers are less
      stable than the global minimum structures, and this energy difference
      approximately increases with the ring size: 17 (S(4)O), 40 (S(5)O), 32 (S(6)O),
      28 (S(7)O), 45 (S(8)O), and 54 kJ mol(-1) (S(9)O). Owing to a favorable pi*-pi*
      interaction, preference for an axial (or endo) conformation is calculated for the
      global energy minima of S(7)O, S(8)O, and S(9)O. Vapor-phase decomposition of
      S(n)O molecules to SO(2) and S(8) is strongly exothermic, whereas the formation
      of S(2)O and S(8) is exothermic if n<7, but slightly endothermic for S(7)O,
      S(8)O, and S(9)O. The calculated vibrational spectra of the most stable isomers
      of S(6)O, S(7)O, and S(8)O are in excellent agreement with the observed data.

PMID- 17013962
TI  - Polymeric organometallic architectures of novel P-Se anions.
AB  - The characterisation of a series of compounds obtained from Woollins' reagent
      (W.R.) offers a novel approach to organometallic coordination polymers. The
      syntheses were achieved by nucleophilic ring-opening reactions of W.R. with metal
      salts and crystallisation using solvent-diffusion techniques. One-dimensional
      coordination polymers are formed as a result, and we demonstrate that the
      dimensionality of the polymers can be influenced by using hydrated metal salts or
      by the construction of heterometallic arrangements.

PMID- 17013963
TI  - The self-ordering properties of novel phthalocyanines with out-of-plane alkyl
      substituents.
AB  - Two novel homologous series of phthalocyanines were prepared from 2,2
      dialkylindane and 2,2-dialkyl-1,3-benzodioxole precursors. It was anticipated
      that attaching alkyl chains to five-membered rings, fused to the peripheral sites
      of the phthalocyanine ring, would result in the adoption of an out-of-plane
      configuration and thereby discourage cofacial aggregation, to provide an analogy
      with picket-fence porphyrins. This strategy proved partially successful. Some
      members of the series of phthalocyanines derived from 2,2-dialkyl-1,3
      benzodioxoles, in which the alkyl chains are linked to the phthalocyanine via a
      cyclic ketal, form spin-coated thin films in which the phthalocyanine cores are
      perfectly isolated. This behaviour is associated with the formation of a
      disordered crystal that appears as a mesophase in the thermal profile of these
      materials. However, the phthalocyanines derived from 2,2-dialkylindanes display a
      columnar mesophase over a wide temperature range, with some liquid crystalline
      derivatives at ambient temperature. A single-crystal X-ray diffraction structure
      of the octahexyl derivative of this series shows how the columnar assembly
      accommodates the out-of-plane alkyl chains by tilting the macrocyclic plane of
      the phthalocyanine components with respect to the axis of the column. This study
      helps to emphasise the importance of both the steric and electronic effects of
      substituents on the packing behaviour of phthalocyanines in the condensed phase,
      and especially the role of electron-donating oxygen atoms directly attached to
      the ring.

PMID- 17013964
TI  - Enyne metathesis-oxidation sequence for the synthesis of 2-phosphono pyrroles:
      proof of the "yne-then-ene" pathway.
AB  - A new tandem reaction sequence has been developed for the synthesis of 2
      phosphono pyrroles. The sequence consists of ring-closing enyne metathesis of a
      substituted aminophosphonate, containing a terminal alkyne and an internal
      alkene, in combination with in situ oxidation of the produced 3-pyrrolines using
      tetrachloroquinone. By analyzing the formation of the end and certain byproducts,
      taking into account the difference in reactivity of different substrates and
      carefully studying spectroscopic data, it was found that the reaction proceeds by
      means of the "yne-then-ene" pathway. During the initiation phase, a new ruthenium
      carbene is formed which continues the propagation cycle.

PMID- 17013965
TI  - Highly selective hydroaminomethylation of internal alkenes to give linear amines.
AB  - The application of phenoxaphosphino-modified Xantphos-type ligands (1-9) in the
      rhodium-catalyzed hydroaminomethylation of internal olefins to give linear amines
      is reported. Excellent chemo- and regioselectivities have been obtained through
      the use of 0.1 mol % [Rh(cod)2]BF(4)/0.4 mol % xantphenoxaphos (1), providing a
      practical and environmentally attractive synthetic route for the preparation of
      amines from internal alkenes. For the first time, both functionalized internal
      olefins and mixtures of internal and terminal olefins have been converted highly
      selectively into linear amines. Investigations of the effects of the calculated
      natural bite angles of ligands on hydroaminomethylation shows that the
      regioselectivity for the linear product follows a similar trend to that seen in
      the hydroformylation of internal alkenes with the aid of these ligands.
      Hydroaminomethylation and each of its individual steps were monitored by high
      pressure infrared spectroscopy. The results suggest that hydroaminomethylations
      take place by a sequential isomerization/hydroformylation/amination/hydrogenation
      pathway.

PMID- 17013966
TI  - A new macrocyclic cryptand with squaramide moieties: an overstructured Cu(II)
      complex that selectively binds halides: synthesis, acid/base- and ligational
      behavior, and crystal structures.
AB  - The synthesis and characterization of the novel 24,29-dimethyl-6,7,15,16
      tetraoxotetracyclo-[19.5.5.0(5,8).0(14,17)]-1,4,9,13,18,21,24,29
      octaazaenatriaconta-Delta(5,8),Delta(14,17)-diene (L) are reported. Molecule L
      incorporates two squaramide functions in a overstructured chain connecting two
      opposite nitrogen atoms of the Me(2)[12]aneN(4) polyaza macrocyclic base to
      obtain a cage topology. The basicity and binding properties of L towards Cu(II)
      were determined by means of potentiometric measurements in aqueous solution
      (298.1+/-0.1 K, I=0.15 mol dm(-3)). Molecule L behaves as a diprotic base under
      the experimental conditions employed and forms only mononuclear Cu(II) complexes
      in which the squaramide moieties are not involved in the stabilization of the
      metal ion that is stabilized by the amine functions of the polyaza base inside
      the three-dimensional cavity. The [CuL](2+) species was tested as a host for the
      series of halide anions. UV-visible spectrophotometric experiments permitted the
      determination of the addition constants of halides to the Cu(II)-complexed
      species. The [CuL](2+) species binds the anions F(-), Cl(-), and Br(-) by forming
      the [CuLX](+) species, but does not bind the biggest I(-) anion. A trend of
      selectivity as a function of the hydrogen-bonding capability as well as the
      dimensions of the anion were established; the maximum value of selectivity was
      for addition of the F(-) anion (log K=4.8). This selectivity is due to the
      presence of the overstructured chain containing the squaramide groups up to the
      Me(2)[12]aneN(4) macrocyclic base. The squaramide groups, by providing hydrogen
      bond contacts, permit the [CuL](2+) species to selectively bind these anions
      through the formation of a hydrogen-bond network with F(-) and Cl(-). The crystal
      structures of the [CuLF](+) and [CuLCl](+) cations support the results obtained
      in aqueous solution.

PMID- 17013967
TI  - Organocatalyzed highly enantioselective direct aldol reactions of aldehydes with
      hydroxyacetone and fluoroacetone in aqueous media: the use of water to control
      regioselectivity.
AB  - An organocatalyst prepared from (2R,3R)-diethyl 2-amino-3-hydroxysuccinate and L
      proline exhibited high regio- and enantioselectivities for the direct aldol
      reactions of hydroxyacetone and fluoroacetone with aldehydes in aqueous media. It
      was found that water could be used to control the regioselectivity. The presence
      of 20-30 mol% of the catalyst afforded the direct aldol reactions of a wide range
      of aldehydes with hydroxyacetone to give the otherwise disfavored products with
      excellent enantioselectivities, ranging from 91 to 99% ee, and high
      regioselectivities. Aldolizations of fluoroacetone with aldehydes mediated by 30
      mol% of the organocatalyst in aqueous media preferentially occurred at the methyl
      group, yielding products with high enantioselectivities (up to 91% ee); however,
      these additions took place dominantly at the fluoromethyl group in THF. Optically
      active 3,5-disubstituted tetrahydrofurans and (2S,4R)-dihydroxy-4-biphenylbutyric
      acid were prepared by starting from the aldol reaction of hydroxyacetone.
      Theoretical studies on the role of water in controlling the regioselectivity
      revealed that the hydrogen bonds formed between the amide oxygen of proline
      amide, the hydroxy of hydroxyacetone, and water are responsible for the
      regioselectivity by microsolvation with explicit one water molecule as a hydrogen
      bond donor and/or an acceptor.

PMID- 17013968
TI  - NMR spectroscopy of laser-polarized (129)Xe under continuous flow: a method to
      study aqueous solutions of biomolecules.

PMID- 17013969
TI  - The benefits of early intervention in obese diabetic patients with FBCx: a new
      dietary fibre.
AB  - BACKGROUND: Obesity and diabetes have become epidemic in the US. Dietary fibres
      have been reported to reduce the absorption of dietary fat, prevent weight gain,
      and reduce blood lipid levels. In the current double-blind study, obese patients
      with type 2 diabetes were recruited for a 3-month study to examine the health
      effects of a new dietary fibre, FBCx. METHODS: Sixty-six participants were
      recruited and were randomized into FBCx or placebo groups. They were instructed
      to take two 1-g tablets per fat-containing meal and not to change their eating
      patterns or daily routine. Three-day dietary records and fasting blood samples
      were collected prior to enrollment in the study and at the end of months 1, 2 and
      3. RESULTS: Dietary records showed that some participants changed their eating
      patterns; therefore body weight data were adjusted according to energy intake. As
      a group, in the 30 days leading into the study, all participants experienced an
      average weight gain of 1.0 +/- 0.4 kg, while those in the placebo group continued
      to gain weight during the study, those in the FBCx group maintained their weight.
      Those in the FBCx group required more energy to maintain their body weight while
      those in the placebo group required less (p < 0.05). Participants with
      hypertriglyceridemia showed a reduction (-0.48 +/- 0.24 mmol/L, - 8.2%) in total
      cholesterol with FBCx, while those with placebo had an increase (0.24 +/- 0.21
      mmol/L, 5.2%, p < 0.05). Adiponectin was increased in the FBCx but reduced in the
      placebo group (p < 0.05). CONCLUSIONS: FBCx has thus shown promising benefits in
      weight maintenance, a reduction of blood lipids and an increase in adiponectin
      levels. It can be easily incorporated into a diabetic management regimen.

PMID- 17013971
TI  - Total synthesis of tubulysin U and V.

PMID- 17013972
TI  - Cocrystallization and encapsulation of a fluorophore with hexameric
      pyrogallol[4]arene nanocapsules: structural and fluorescence studies.

PMID- 17013973
TI  - Octameric and decameric aluminophosphates.

PMID- 17013974
TI  - Electrochemical switching and size selection in cucurbit[8]uril-mediated
      dendrimer self-assembly.

PMID- 17013976
TI  - Therapeutic anti-tumor immunity triggered by injections of immunostimulating
      single-stranded RNA.
AB  - Stabilized synthetic RNA oligonucleotides (ORN) and protected messenger RNA
      (mRNA) were recently discovered to possess an immunostimulatory capacity through
      their recognition by TLR 7 and 8. We wanted to find out whether this danger
      signal is capable of triggering anti-tumor immunity when injected locally into an
      established tumor. Using the mouse glioma tumor cell line SMA-560 in syngenic
      VM/Dk mice, we were able to show that intra-tumor injections of protamine
      stabilized mRNA do indeed induce tumor regression and long-term anti-tumor
      immunity. Residual RNA-injected tumors show CD8 infiltration. Distant injections
      of protamine-protected mRNA and intra-tumor injection of naked mRNA also result
      in anti-tumor immunity. Although they are strong danger signals, RNA are labile
      molecules with a short half-life: they do not trigger side effects such as long
      term, uncontrolled immunostimulation evidenced by splenomegaly in CpG DNA-treated
      mice. In conclusion, RNA molecules are potent and safe danger signals that are
      relevant for active immunotherapy strategies aimed at the eradication of solid
      tumors.

PMID- 17013977
TI  - Normal responses to specific NOD1 ligands.

PMID- 17013979
TI  - Natural killer (NK) cell functions can be strongly boosted by activated dendritic
      cells (DC).

PMID- 17013980
TI  - Role of MyD88 and Trif in acute allograft rejection: glass half full or empty?

PMID- 17013981
TI  - In vitro (1)H NMR studies of RD human cell infection with echovirus 11.
AB  - The effects of echovirus 11 infection on RD human cell line (derived from
      rhabdomyosarcoma) were studied using (1)H NMR spectroscopy and optical
      microscopy. Both uninfected and infected cells consumed glucose and produced
      lactate, acetate and formate as extracellular metabolites. In infected whole
      cells, phosphocholine and uridine-sugar were observed in addition to the
      metabolites observed in uninfected cells. Water-soluble intracellular metabolites
      of infected cells showed glutamine, phosphocholine and glycine which were not
      observed in uninfected cells. Cellular metabolites except lipid components
      gradually decreased and disappeared during 24-48 h of viral infection. The
      quantity of lipid components in infected cells was comparable with that in
      uninfected cells, indicating that echovirus 11 does not utilize cell lipid
      molecules. Unlike optical microscopy, (1)H NMR spectroscopy identified early
      stages of infection through metabolic changes. These results may have potential
      implications in probing virus-cell interactions using NMR-based metabolomics.

PMID- 17013982
TI  - Topography of plasma membrane microdomains and its consequences for mast cell
      signaling.
AB  - Thy-1 (CD90) is a glycoprotein bound to the plasma membrane by a GPI anchor.
      Aggregation of Thy-1 in mast cells and basophils induces activation events
      independent of the expression of Fcepsilon receptor I (FcepsilonRI). Although we
      and others have previously suggested that plasma membrane microdomains called
      lipid rafts are implicated in both Thy-1 and FcepsilonRI signaling, properties of
      these microdomains are still poorly understood. In this study we used rat
      basophilic leukemia cells and their transfectants expressing both endogenous Thy
      1.1 and exogenous Thy-1.2 genes and analyzed topography of the Thy-1 isoforms and
      Thy-1-induced signaling events. Light microscopy showed that both Thy-1 isoforms
      were in the plasma membrane distributed randomly and independently. Electron
      microscopy on isolated membrane sheets and fluorescence resonance energy transfer
      analysis indicated cross-talk between Thy-1 isoforms and between Thy-1 and
      FcepsilonRI. This cross-talk was dependent on actin filaments. Thy-1 aggregates
      colocalized with two transmembrane adaptor proteins, non-T cell activation linker
      (NTAL) and linker for activation of T cells (LAT), which had been shown to
      inhabit different membrane microdomains. Thy-1 aggregation led to tyrosine
      phosphorylation of these two adaptors. The combined data indicate that aggregated
      GPI-anchored proteins can attract different membrane proteins in different
      clusters and thus can trigger different signaling pathways.

PMID- 17013983
TI  - A versatile approach for the preparation of thermosensitive PNIPAM core-shell
      microgels with nanoparticle cores.

PMID- 17013984
TI  - A weakly clustered N terminus inhibits Abeta(1-40) amyloidogenesis.

PMID- 17013985
TI  - Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes
      induces the activated FDC phenotype associated with secondary follicle
      development.
AB  - Follicular dendritic cell (FDC)-FcgammaRIIB levels are up-regulated 1-3 days
      after challenge of actively immunized mice with Ag. This kinetics suggested that
      memory cells are not driving this response, prompting the hypothesis that immune
      complex (IC)-FDC interactions lead to FDC activation. To test this, mice
      passively immunized with anti-OVA Ab were OVA challenged to produce IC. After 3
      days, levels of IC, FcgammaRIIB, ICAM-1, and VCAM-1 on FDC were analyzed. FDC
      were also stimulated with IC in vitro, and mRNA for FcgammaRIIB, ICAM-1, and VCAM
      1 was quantified by quantitative RT-PCR. IC labeling in passively immunized WT
      and FcgammaRIIB-/- mice revealed five to six FDC-reticula per LN midsagittal
      section. In WT mice, these IC-bearing FDC-reticula corresponded with FDC-reticula
      labeling for FcgammaRIIB, ICAM-1, and VCAM-1. Increases in these molecules on IC
      stimulated FDC were confirmed by flow cytometry. In marked contrast, in
      FcgammaRIIB-/- mice, no increased VCAM-1 or ICAM-1 was seen on IC-bearing FDC
      reticula or on purified FDC. Addition of IC in vitro resulted in dramatic
      increases in mRNA for FcgammaRIIB, ICAM-1 and VCAM-1 in WT FDC, but not in FDC
      from FcgammaRIIB-/- mice, 2.4G2-pretreated WT FDC, B cells, or macrophages. Thus,
      although FDC-FcgammaRIIB was not essential for IC trapping, engagement of FDC
      FcgammaRIIB with IC initiated an FDC activation pathway.

PMID- 17013987
TI  - Immunoregulatory function of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone
      marrow where they closely interact with hematopoietic stem cells and support
      their growth and differentiation. MSC can differentiate into multiple mesenchymal
      and non-mesenchymal lineages, providing a promising tool for tissue repair. In
      addition, MSC suppress many T cell, B cell and NK cell functions and may affect
      also dendritic cell activities. Due to their limited immunogenicity, MSC are
      poorly recognized by HLA-incompatible hosts. Based on these unique properties,
      MSC are currently under investigation for their possible use to treat immuno
      mediated diseases. However, both their condition of immunoprivilege and their
      immunosuppressive function have recently been challenged when analyzed under
      particular experimental conditions. Thus, it is likely that MSC effects on the
      immune system may be deeply influenced not only by cell-to-cell interactions, but
      also by environmental factors shaping their phenotype and functions.

PMID- 17013988
TI  - Induction of long-lasting multi-specific CD8+ T cells by a four-component DNA
      MVA/HIVA-RENTA candidate HIV-1 vaccine in rhesus macaques.
AB  - As a part of a long-term effort to develop vaccine against HIV-1 clade A inducing
      protective T cell responses in humans, we run mutually complementing studies in
      humans and non-human primates (NHP) with the aim to maximize vaccine
      immunogenicity. The candidate vaccine under development has four components,
      pTHr.HIVA and pTH.RENTA DNA, and modified vaccinia virus Ankara (MVA).HIVA and
      MVA.RENTA, delivered in a heterologous DNA prime-MVA boost regimen. While the
      HIVA (Gag/epitopes) components have been tested in NHP and over 300 human
      subjects, we plan to test in humans the RENTA (reverse transcriptase, gp41, Nef,
      Tat) vaccines designed to broaden HIVA-induced responses in year 2007. Here, we
      investigated the four-component vaccine long-term immunogenicity in Mamu-A*01
      positive rhesus macaques and demonstrated that the vaccine-induced T cells were
      multi-specific, multi-functional, readily proliferated to recall peptides and
      were circulating in the peripheral blood of vaccine recipients over 1 year after
      vaccine administration. The consensus clade A-elicited T cells recognized 50% of
      tested epitope variants from other HIV-1 clades. Thus, the DNA-MVA/HIVA-RENTA
      vaccine induced memory T cells of desirable characteristics and similarities to
      those induced in humans by HIVA vaccines alone; however, single-clade vaccines
      may not elicit sufficiently cross-reactive responses.

PMID- 17013989
TI  - Immunisation with recombinant modified vaccinia virus Ankara expressing HIV-1 gag
      in HIV-1-infected subjects stimulates broad functional CD4+ T cell responses.
AB  - Virus-specific CD4+ T cells with IL-2-secreting and/or proliferative capacity are
      detected readily in HIV-1-infected long-term nonprogressors and rarely in persons
      with untreated progressive infection. The contribution of these cells to viraemia
      control is uncertain, but this question might be addressed in clinical
      therapeutic vaccination studies. However, the quality of T helper responses
      induced by currently available HIV-1 vaccine candidates has not been explored in
      depth. We determined the effect of vaccination with modified vaccinia virus
      Ankara (MVA) expressing HIV-1 gag p24/p17 (MVA.HIVA) on HIV-1-specific CD4+ T
      cell responses in 16 chronically infected, highly active antiretroviral therapy
      (HAART)-treated subjects using CD8-depleted IFN-gamma ELISPOT assays,
      intracellular cytokine staining assays for IL-2 and IFN-gamma, and a CFSE-based
      proliferation assay. Gag-specific CD4+ T cell responses were significantly
      increased in magnitude and breadth after vaccination and targeted both known and
      new epitopes, several of which were also recognised by healthy HIV-uninfected
      volunteers immunised with the same vaccines. The frequencies of CD4+ T cells
      expressing IL-2 or IFN-gamma, alone or simultaneously, were also augmented. These
      findings indicate that functional virus-specific T helper cells can be boosted by
      vaccination in chronic HIV-1 infection. Further evaluation of their role in
      viraemia control is warranted.

PMID- 17013990
TI  - ICOS cooperates with CD28, IL-2, and IFN-gamma and modulates activation of human
      naive CD4+ T cells.
AB  - Several sets of data indicate that ICOS regulates cytokine production in
      activated T cells, but is less effective on naive T cells. This work evaluates
      ICOS function in human naive CD4+ T cells through an assessment of the effect of
      soluble forms of the ICOS and CD28 physiological ligands on activation driven by
      anti-CD3 mAb. ICOS strikingly potentiated secretion of IL-2, IFN-gamma, IL-10,
      and TNF-alpha, but not IL-4, promoted by optimal stimulation of CD3+CD28, and it
      was the key switching-factor of activation when cells received suboptimal
      stimulation of CD3+CD28 or stimulation of CD3 alone in the presence of exogenous
      IL-2. In these conditions, blockade of IL-2 and IFN-gamma showed that ICOS builds
      up a positive feedback loop with IFN-gamma, which required IL-2 and was inhibited
      by IL-4. By contrast, in the absence of CD28 triggering or exogenous IL-2, ICOS
      induced costimulation mainly supported expression of TGF-beta1 and FoxP3 and
      differentiation of regulatory T cells capable to inhibit proliferation of naive
      CD4+ T cells driven by allogeneic cells. These data suggest that ICOS favors
      differentiation of Th effector cells when cooperates with appropriate activation
      stimuli such as CD3+CD28 or CD3+IL-2, whereas it supports differentiation of
      regulatory T cells when costimulatory signals are insufficient.

PMID- 17013991
TI  - Parallel protein and transcript profiles of FSHD patient muscles correlate to the
      D4Z4 arrangement and reveal a common impairment of slow to fast fibre
      differentiation and a general deregulation of MyoD-dependent genes.
AB  - Here, we present the first study of a human neuromuscular disorder at
      transcriptional and proteomic level. Autosomal dominant facio-scapulo-humeral
      muscular dystrophy (FSHD) is caused by a deletion of an integral number of 3.3-kb
      KpnI repeats inside the telomeric region D4Z4 at the 4q35 locus. We combined a
      muscle-specific cDNA microarray platform with a proteomic investigation to
      analyse muscle biopsies of patients carrying a variable number of KpnI repeats.
      Unsupervised cluster analysis divides patients into three classes, according to
      their KpnI repeat number. Expression data reveal a transition from fast
      glycolytic to slow-oxidative phenotype in FSHD muscle, which is accompanied by a
      deficit of proteins involved in response to oxidative stress. Besides, FSHD
      individuals show a disruption in the MyoD-dependent gene network suggesting a
      coregulation at transcriptional level during myogenesis. We also discuss the
      hypothesis that D4Z4 contraction may affect in trans the expression of a set of
      genes involved in myogenesis, as well as in the regeneration pathway of satellite
      cells in adult tissue. Muscular wasting could result from the inability of
      satellite cells to successfully differentiate into mature fibres and from the
      accumulation of structural damages caused by a reactive oxygen species (ROS)
      imbalance induced by an increased oxidative metabolism in fibres.

PMID- 17013993
TI  - Advance market commitments for vaccines against neglected diseases: estimating
      costs and effectiveness.
AB  - The G8 is considering committing to purchase vaccines against diseases
      concentrated in low-income countries (if and when desirable vaccines are
      developed) as a way to spur research and development on vaccines for these
      diseases. Under such an 'advance market commitment,' one or more sponsors would
      commit to a minimum price to be paid per person immunized for an eligible
      product, up to a certain number of individuals immunized. For additional
      purchases, the price would eventually drop to close to marginal cost. If no
      suitable product were developed, no payments would be made. We estimate the offer
      size which would make revenues similar to the revenues realized from investments
      in typical existing commercial pharmaceutical products, as well as the degree to
      which various model contracts and assumptions would affect the cost-effectiveness
      of such a commitment. We make adjustments for lower marketing costs under an
      advance market commitment and the risk that a developer may have to share the
      market with subsequent developers. We also show how this second risk could be
      reduced, and money saved, by introducing a superiority clause to a commitment.
      Under conservative assumptions, we document that a commitment comparable in value
      to sales earned by the average of a sample of recently launched commercial
      products (adjusted for lower marketing costs) would be a highly cost-effective
      way to address HIV/AIDS, malaria, and tuberculosis. Sensitivity analyses suggest
      most characteristics of a hypothetical vaccine would have little effect on the
      cost-effectiveness, but that the duration of protection conferred by a vaccine
      strongly affects potential cost-effectiveness. Readers can conduct their own
      sensitivity analyses employing a web-based spreadsheet tool.

PMID- 17013994
TI  - Arg753Gln TLR-2 polymorphism in familial mediterranean fever: linking the
      environment to the phenotype in a monogenic inflammatory disease.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disease
      common in eastern Mediterranean populations. The most severe complication is the
      development of secondary amyloidosis. Toll-like receptor (TLR-2) plays a critical
      role in linking the recognition of microbes to immune activation. We investigated
      whether the Arg753Gln TLR2 polymorphism affected the development of secondary
      amyloidosis in patients with FMF. METHODS: We studied 75 patients with FMF, 40
      patients with FMF who developed secondary amyloidosis, and 116 healthy controls.
      TLR2 gene Arg753Gln mutations were analyzed with a polymerase chain reaction
      restriction fragment length polymorphism method. RESULTS: The frequency of the
      Arg753Gln TLR2 polymorphism among the Turkish population was 6%, whereas it was
      25.2% among patients with FMF (p < 0.01). The difference of the frequency of the
      polymorphism between FMF patients with and without amyloidosis was significant:
      15/40 (37.5%) and 14/75 (18.6%), respectively (p = 0.02). CONCLUSION: The
      Arg753Gln polymorphism may affect the severity of this monogenic disease by
      influencing the innate immune response to pathogens. The presence of the
      polymorphism may influence the phenotype of FMF in geographic areas where
      bacterial insult is more common.

PMID- 17013995
TI  - Influence of ibuprofen-arginine on serum levels of nitric oxide metabolites in
      patients with chronic low back pain--a single-blind, placebo controlled pilot
      trial (ISRCTN18723747).
AB  - OBJECTIVE: To determine whether ibuprofen-arginine has a cyclooxygenase
      independent pain modulating property in addition to its known antiinflammatory
      effect. METHODS: Patients with chronic low back pain were randomly divided into 2
      groups treated either with oral ibuprofen-arginine (400 mg) or with placebo.
      Blood was drawn from study subjects before, during, and after treatment and they
      were asked each time about the intensity of their pain. Concentrations of nitric
      oxide (NO) metabolites were determined. RESULTS: Twenty minutes after intake of
      ibuprofen-arginine, but not after placebo, there was a relevant and significant
      reduction of NO metabolites in serum. In both groups there was significant
      analgesic effect compared to baseline. CONCLUSION: An early lowering of the serum
      NO metabolite levels after ibuprofen-arginine administration could be detected in
      patients with chronic low back pain.

PMID- 17013996
TI  - Prevalence of knee osteoarthritis in the United States: arthritis data from the
      Third National Health and Nutrition Examination Survey 1991-94.
AB  - OBJECTIVE: To estimate the US national prevalence of tibiofemoral radiographic
      knee osteoarthritis (RKOA) with and without symptoms, and its influence on
      functional tasks. METHODS: Radiographic and interview data from the National
      Health and Nutrition Examination Survey (NHANES III), a nationally representative
      cross-sectional health examination survey, were used to estimate lifetime RKOA
      prevalence in adults age 60 years and older. Demographic trends, self-reported
      activity limitations, physical performance test results, and patterns of recent
      analgesic use were analyzed. RESULTS: Among US adults, the prevalence of RKOA and
      symptomatic RKOA was 37.4% and 12.1%, respectively. RKOA prevalence was greater
      among women than men (42.1% vs 31.2%). Women had significantly more Kellgren
      Lawrence Grade 3-4 changes (12.9% vs 6.5% in men). However, symptomatic RKOA
      prevalence did not differ by sex. Additionally, some 1.6% of US adults had knee
      joint replacement. Multivariable analysis showed significantly higher odds of
      both RKOA and symptomatic RKOA with greater body mass index (BMI > or = 30),
      greater age, non-Hispanic Black race/ethnicity, and among men with manual labor
      occupations. Only symptomatic RKOA was significantly associated with self
      reported activity limitations: difficulty walking, stooping, standing from a
      seated position, and stair climbing. Adults with symptomatic RKOA used
      significantly more assistive walking devices, had slower measured gait
      velocities, and used significantly more prescription nonsteroidal
      antiinflammatory drugs and prescription narcotics, and nonprescription
      acetaminophen. CONCLUSION: NHANES III data provide an overall national assessment
      of the prevalence, demographic distributions, and functional impact of
      symptomatic knee OA, which affects more than 1 in 10, or 4.3 million older US
      adults.

PMID- 17013997
TI  - Psoriasis induced by tumor necrosis factor-alpha antagonist therapy: a case
      series.
AB  - OBJECTIVE: Although tumor necrosis factor-alpha (TNF-alpha) antagonists are
      effective in the treatment of refractory psoriasis, some cases have suggested
      that psoriasis might be induced as a result of treatment prescribed mainly for
      rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. To investigate
      anti-TNF-alpha induced psoriasis, we conducted a systematic analysis of the 6
      cases we observed among our inflammatory patient cohort treated with anti-TNF
      alpha (infliximab or etanercept). METHODS: We report 6 cases of psoriasis with
      onset during TNF-alpha antagonist therapy (infliximab and etanercept);
      characteristics and skin lesions are described. RESULTS: No patient had a
      personal or family history of psoriasis. The development of psoriasis was seen in
      all the types of inflammatory diseases we treated with TNF-alpha antagonists.
      There was great variation in the age of affected patients and in the onset of
      psoriasis after initiation of TNF-alpha antagonists. Both TNF-alpha antagonists
      studied were associated with development of psoriasis. In 2 cases psoriasis was
      associated with 2 different TNF-alpha antagonists in the same patient. In half
      our patients, skin lesions started in the inguinal and pubic regions, but
      palmoplantar pustulosis was also common. In half the cases, skin lesions
      responded favorably with topical agents despite continuation of TNF-alpha
      antagonist therapy. CONCLUSION: In light of previously published cases describing
      psoriasis or psoriasiform lesions after TNF-alpha antagonist therapy, our series
      strongly confirms that TNF-alpha antagonists may induce psoriasis in some
      patients. Further studies are needed to identify risk factors for TNF-alpha
      antagonist induced psoriasis.

PMID- 17013998
TI  - Development and validation of a simple tape-based measurement tool for recording
      cervical rotation in patients with ankylosing spondylitis: comparison with a
      goniometer-based approach.
AB  - OBJECTIVE: To compare a tape-based tool for measuring cervical mobility in
      patients with ankylosing spondylitis (AS) with the widely practiced goniometer
      based approach. METHODS: We developed a novel tape-based approach to measurement
      of lateral cervical rotation of the neck that is minimally affected by
      flexion/extension movements of the neck. This requires measurement of the
      difference between a mark at the suprasternal notch and the tragus of the ear.
      Rotation score is measured in centimeters and constitutes the difference in
      length between the 2 extremes of cervical rotation
      (http://www.arthritisdoctors.org/researcher.html). We assessed the tape-based and
      goniometer-based methods in a total of 263 patients from 3 countries, Canada (n =
      205), Australia (n = 29), and Colombia (n = 29), that included patients from
      community and tertiary-based practice. Intra- and interobserver reliability was
      assessed in a subset of 44 patients by ANOVA and a 2-way mixed effects model. The
      Bath AS Disease Activity (BASDAI) and Function (BASFI) Indices, and the modified
      Stoke AS Spinal Score (mSASSS), were also recorded to assess construct validity
      by correlation coefficient and regression analysis. Responsiveness was assessed
      in a subset of 33 patients that were either randomized to anti-tumor necrosis
      factor-a therapy:placebo (n = 22) or received open label infliximab (n = 4) or
      pamidronate (n = 7) over a period of 24 weeks. RESULTS: Scores obtained with the
      tape-based method were normally distributed, while those obtained using the
      goniometer were skewed towards normal values. Reliability for the goniometer
      based approach was excellent [intraclass correlation coefficient (ICC) > 0.90]
      and very good for the tape-based approach (ICC > 0.80). Significant correlations
      were noted between age, disease duration, function and structural damage scores,
      and scores obtained with both methods. Responsiveness was high using raw scores
      obtained with the goniometer (standardized response mean > 0.80) but was not
      evident when the grading scheme proposed for the Bath AS Metrology Index (BASMI)
      was employed. CONCLUSION: The tape-based approach we describe provides a simple,
      feasible, and reliable index of cervical rotation that is comparable to the
      information obtained from the use of a goniometer. If the goniometer-based
      approach is used, raw scores should be used in the calculation of responsiveness
      rather than the grading scheme suggested in the BASMI.

PMID- 17013999
TI  - Identification of the most common problems by patients with ankylosing
      spondylitis using the international classification of functioning, disability and
      health.
AB  - OBJECTIVE: The International Classification of Functioning, Disability and Health
      (ICF) aims to classify functioning and health by a number of categories divided
      over 3 components: body functions and body structures, participation and
      activities, and environmental factors. We identified the common health problems
      of patients with ankylosing spondylitis (AS) based on the ICF from the
      perspective of the patient. METHODS: During structured interviews with the
      extended ICF checklist, trained assessors collected data from 111 patients with
      AS. ICF categories identified by more than 5% of the patients as at least mildly
      impaired or restricted were selected. Categories identified by less than 5% were
      removed. Additional impairments/restrictions reported by more than 5% of the
      patients, after the structured interviews and not yet included in the checklist,
      were added. RESULTS: One hundred nineteen (72%) out of 165 categories of the
      extended ICF checklist were identified to be at least mildly impaired or
      restricted. Within each of the 4 components of the ICF, at least one-third of the
      categories were impaired or restricted for more than 50% of the patients. Thirty
      nine (33%) categories were related to movement and mobility. Within the component
      "environmental factors" the categories "support of immediate family" and "health
      professionals" were the most important facilitators, "climate" was the most
      important barrier. Eight impairments were additionally mentioned as relevant.
      These were hierarchically lower levels of ICF categories previously included and
      they were added. CONCLUSION: One hundred twenty-seven ICF categories represent
      the comprehensive classification of functioning in AS from the patients'
      perspective. The results underscore the need to address the 4 ICF components when
      classifying functioning and to emphasize that functioning implies more than
      physical functioning.

PMID- 17014001
TI  - Association between antiphospholipid antibodies and recurrent fetal loss in women
      without autoimmune disease: a metaanalysis.
AB  - OBJECTIVE: To assess the strength of association between recurrent fetal loss
      (RFL) and presence of antiphospholipid antibodies (aPL) in women without
      autoimmune disease, and to examine whether magnitude of association varies
      according to type or titer of antibody and timing of fetal loss. METHODS: We
      searched Medline and Current Contents for articles published between 1975 and
      2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks)
      RFL associated with various aPL. Published case-control, cohort, and cross
      sectional studies rated moderate or strong were included in our metaanalysis.
      Pooled odds ratios with 95% CI were generated using the random-effects models
      with Cochrane Review Manager software. RESULTS: Our analysis included 25 studies.
      Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30
      26.45); the association of LAC was stronger than that of any other aPL. IgG
      anticardiolipin antibodies (aCL), when combining all titers, were associated with
      both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65).
      Restricting analysis to include only women with moderate to high titers increased
      the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to
      extract data on isolated low IgG aCL positivity. IgM aCL were associated with
      late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between
      early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53).
      CONCLUSION: The magnitude of the association between aPL and RFL varies according
      to type of aPL. More data on the relationship between recurrent fetal loss and
      isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of
      testing for anti-Beta2-glycoprotein I antibodies remains to be determined.

PMID- 17014002
TI  - Predictors of carotid atherosclerosis in systemic lupus erythematosus.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at increased risk
      for cardiovascular and cerebrovascular events, even after adjustment for
      traditional risk factors. We examined the association of traditional risk
      factors, novel markers of cardiovascular disease (C-reactive protein,
      homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, fibrinogen), and
      markers indicative of SLE activity (including C3, C4, anti-dsDNA, and prednisone
      use) with the presence of significant plaque on carotid duplex imaging. METHODS:
      Six hundred five patients with SLE enrolled in the Hopkins Lupus Cohort Study
      (92% female, 38% African-American) underwent carotid duplex testing.
      Prospectively gathered clinical, laboratory, and serologic data from their
      quarterly followup visits in the Hopkins Lupus Cohort were used in the analyses.
      For predictors that varied over time, such as cholesterol, the mean values during
      cohort participation were calculated for the analysis. Informed consent was
      obtained from all patients. RESULTS: The presence of carotid plaque was strongly
      associated with age, ranging from 1% among those less than 30 years of age to 61%
      among those 60 years or older. After adjusting for age, there were moderate or
      strong associations of carotid plaque with male gender (age-adjusted risk 25% vs
      13%; p = 0.051), hypertension (age-adjusted risk 18% vs 8%; p = 0.0001), diabetes
      mellitus (age-adjusted risk 19% vs 13%; p = 0.075), C3 > 120 mg/dl (age-adjusted
      risk 18% vs 11% and 14% for normal and low C3, respectively; p = 0.046), serum
      creatinine > 1.3 (age-adjusted risk 32% vs 13%; p = 0.039), and mean systolic
      blood pressure > 140 (age-adjusted risk 23% vs 13%; p = 0.028). There was no
      strong evidence of an association between plaque and SLE disease activity (age
      adjusted risk 14% among those with adjusted mean SLEDAI > 3 vs 14% among those
      with lower SLEDAI) or with time since SLE diagnosis (age-adjusted risk 12%, 14%,
      and 16% among those with SLE for < 2, 2-8, and > 8 years, respectively; p =
      0.49). CONCLUSION: Traditional cardiovascular risk factors were associated with
      carotid plaque in SLE. However, SLE disease activity and duration of SLE are not
      strongly associated with carotid plaque. A "lupus factor" separate from
      traditional risk factors remains unidentified.

PMID- 17014003
TI  - Declining trend in the incidence of rheumatoid factor-positive rheumatoid
      arthritis in Finland 1980-2000.
AB  - OBJECTIVE: To investigate trends in the incidence of rheumatoid arthritis (RA) in
      Finland. METHODS: We studied all the subjects entitled to receive drug
      reimbursement for chronic inflammatory joint diseases in 5/21 central hospital
      districts (population base about 1 million adults) in Finland during 2000. The
      incidence rates and the mean age at disease onset were compared with those from
      1980, 1985, 1990, and 1995. RESULTS: A total of 714 subjects were entitled to
      drug reimbursement for chronic inflammatory joint disease that had started at the
      age of 16 or over. Of them, 321 satisfied the American College of Rheumatology
      classification criteria for RA, 198 had spondyloarthropathy, and 195 had
      undifferentiated oligo- or polyarthritis. The incidence of RA was 29.1/100,000
      (95% CI 26.0-32.5); the figures for rheumatoid factor (RF)-positive RA and RF
      negative RA were 18.2 (95% CI 15.8-21.0) and 10.8 (95% CI 9.0-12.9)/100,000,
      respectively. The incidence of RA was 36.9 (95% CI 32.1-42.2)/100,000 among women
      and 20.8 (95% CI 17.2-25.1)/100,000 among men. The age- and sex-adjusted
      incidence rate ratio declined from 1.00 in the referent year 1980 to 0.55 (95% CI
      0.46-0.66) in 2000. A declining trend was evident for the incidence of RF
      positive RA (p < or = 0.001). CONCLUSION: We verified the declining trend for the
      incidence of RF-positive RA in both sexes in Finland. Although the etiology of RA
      remains unknown, public health measures may reduce the risk of RA in the general
      population.

PMID- 17014004
TI  - Retention rates of tumor necrosis factor blockers in daily practice in 770
      rheumatic patients.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) blockers are efficacious in clinical
      trials in rheumatic diseases. However, their efficacy in daily practice,
      depending on the specific diagnosis or the use of concomitant therapy, remains to
      be confirmed. Our objective was to evaluate TNF blocker retention rates and their
      predisposing factors in daily practice. METHODS: Retrospective evaluation of all
      TNF blocker therapies in one center. Retention rate was evaluated using a Kaplan
      Meier survival data analysis technique in which the event was discontinuation of
      the drug due to inefficacy or toxicity with log-rank tests and a Cox proportional
      hazards regression model. RESULTS: From 1997 to 2004, 770 patients with
      inflammatory rheumatism received at least one TNF blocker; 142 received more than
      one agent (975 treatment courses: 493 etanercept, 335 infliximab, 147
      adalimumab). The underlying disease was mainly rheumatoid arthritis (RA), found
      in 57.1% of patients, and spondyloarthropathies (SpA) in 37.7%. The percentage of
      patients receiving the same treatment at Month 12, 24, and 36 was 64.0%, 50.3%,
      and 39.4%, respectively. No difference between the 3 TNF blockers was found (p =
      0.48). The retention rate was longer for the first treatment course [hazard ratio
      (HR) 2.17, 95% confidence interval (95% CI) 1.82-2.58, p < 0.0001]; longer for
      patients with SpA (HR 1.60, 95% CI 1.20-2.13, p = 0.001); and longer without
      concomitant DMARD (HR 0.70, 95% CI 0.51-0.97, p = 0.03). CONCLUSION: Our results
      indicate a lower retention rate of TNF blockers in daily practice compared with
      clinical trials, with no difference between the 3 currently available agents.
      Moreover, results suggest greater benefit in SpA. The role of concomitant DMARD
      remains to be confirmed.

PMID- 17014005
TI  - Modest but sustained increase of serum high density lipoprotein cholesterol
      levels in patients with inflammatory arthritides treated with infliximab.
AB  - OBJECTIVE: Tumor necrosis factor-a (TNF-a) is a key cytokine in the pathogenesis
      of chronic inflammatory arthritides, has proatherogenic effects, and may be
      positively correlated with impairment of the action of insulin. Patients with
      chronic inflammatory arthritides have an increased risk for cardiovascular
      diseases. We assessed whether anti-TNF-a treatment modifies the unfavorable lipid
      profile induced by chronic inflammatory arthritides. METHODS: Sixty patients (24
      with rheumatoid arthritis, 26 ankylosing spondylitis, and 10 psoriatic arthritis)
      receiving infliximab because of ongoing disease activity despite disease
      modifying drugs (DMARD) were prospectively studied for 6 months. Lipid profile,
      total cholesterol/high density lipoprotein cholesterol (TC/HDL-C), and low
      density lipoprotein cholesterol (LDL-C)/HDL-C ratios, as well as disease activity
      indices (DAS28 and BASDAI), were assessed. RESULTS: A sustained increase of serum
      HDL-C was observed [mean increase (95% CI)] 5 (3-7) mg/dl, 3.5 (1-6) mg/dl, and 3
      (1-5) mg/dl at 1, 3, and 6 months, respectively (p < 0.01). Compared to
      nonresponders, HDL-C increased significantly more in EULAR or BASDAI responders
      (0.8 vs 5.8 mg/dl; p = 0.05). Serum TC was significantly increased [11 (4-8)
      mg/dl; p = 0.001] only after the first month of treatment. TC/HDL-C and LDL-C/HDL
      C decreased only after the first month [0.3 (0.1-0.4), p < 0.01, and 0.2 (0.1
      0.4), p < 0.01, respectively]. For patients with baseline LDL-C > 130 mg/dl, LDL
      C/HDL-C decreased (p < 0.05) during the whole study period and TC/HDL-C decreased
      (p < 0.05) at 1 and 3 months. CONCLUSION: Anti-TNF-a treatment in patients with
      chronic inflammatory arthritides induces a modest, but sustained, increase in
      serum HDL-C levels, which may have a favorable effect in reducing the
      cardiovascular risk in these patients.

PMID- 17014006
TI  - Reduction of inflammatory biomarker response by abatacept in treatment of
      rheumatoid arthritis.
AB  - OBJECTIVE: Abatacept, a soluble selective costimulation modulator, selectively
      modulates T cell activation via the CD80/CD86:CD28 costimulation pathway. Data
      from a Phase II trial showed efficacy in patients with active rheumatoid
      arthritis (RA) and inadequate response to methotrexate when treated with
      abatacept (10 mg/kg or 2 mg/kg). To determine the mechanism of action of
      abatacept, we analyzed changes in the serum levels of inflammatory biomarkers in
      the patients enrolled in this trial. RESULTS: Following 12 months' treatment,
      serum levels of interleukin 6 (IL-6), soluble IL-2 receptor, C-reactive protein,
      soluble E-selectin, and soluble intercellular adhesion molecule-1 were
      significantly lower in patients receiving abatacept 10 mg/kg versus placebo.
      Smaller reductions in tumor necrosis factor-a and rheumatoid factor were also
      observed in the abatacept 10 mg/kg group compared with the placebo group.
      Although there was no evidence for efficacy of the 2 mg/kg dose, small reductions
      in inflammatory biomarkers at this dosage support the biologic effect of this
      therapy. CONCLUSION: These findings reveal the antiinflammatory and
      immunomodulatory effects of abatacept in patients with RA, and are consistent
      with the concept that modulating T cell activation improves clinical signs and
      symptoms and inhibits the progression of structural damage. These data suggest
      that selective modulation of the CD80/CD86:CD28 pathway with abatacept may affect
      several inflammatory cell types and cytokines that are involved in the
      proinflammatory cascade.

PMID- 17014007
TI  - The management of gout: it should be crystal clear.

PMID- 17014008
TI  - Diagnosis of Wegener's granulomatosis in the ANCA era.

PMID- 17014009
TI  - Magnetic resonance imaging in rheumatologic practice: low field or standard.

PMID- 17014010
TI  - The healing power of time: the case of lateral epicondylitis.

PMID- 17014011
TI  - Collateral benefits of fish oil therapy for rheumatoid arthritis.

PMID- 17014012
TI  - Should we be using intraarticular tumor necrosis factor blockade in inflammatory
      monoarthritis?

PMID- 17014013
TI  - sE-Selectin expression and A561C polymorphism in relation to rheumatoid arthritis
      clinical activity.
AB  - OBJECTIVE: To investigate the relationship of A561C polymorphism and sE-selectin
      levels with rheumatoid arthritis (RA) clinical activity. METHODS: In a case
      control study, we compared 60 patients with RA and 60 healthy subjects. Patients
      fulfilled the 1987 American College of Rheumatology criteria. Soluble E-selectin
      levels were measured from serum samples using the ELISA kit. We investigated E
      selectin A561C polymorphism by the restriction fragment length polymorphism
      polymerase chain reaction (RFLP-PCR) technique. The disease activity was recorded
      with Spanish Health Assessment Questionnaire Disability Index (HAQ-DI), Spanish
      Arthritis Impact Measurement Scales (AIMS), and Disease Activity Score (DAS28)
      scores. A p value < 0.05 was considered significant. RESULTS: Patients with RA
      showed higher sE-selectin levels than controls (mean 91.7 vs 39 ng/ml; p =
      0.002). A positive correlation between sE-selectin and rheumatoid factor (RF),
      erythrocyte sedimentation rate (ESR), Spanish HAQ-DI, and DAS28 scores was found.
      The E-selectin polymorphism analysis showed diminished frequency in RA of
      heterozygous A/C genotype and increased frequency of homozygous wild-type A/A
      genotype (p = 0.043, OR 1.45; 95% CI 1.125-16.167) versus A/C and A/A genotype in
      healthy subjects. No significant association between A561C polymorphism and
      clinical activity was present. CONCLUSION: The sE-selectin, RF, and ESR, in
      addition to clinical indices, were associated with clinical activity in RA. We
      highlighted the presence of A/A genotype A561C polymorphism in our patients with
      RA.

PMID- 17014014
TI  - Autoantibodies against C-reactive protein: clinical associations in systemic
      lupus erythematosus and primary antiphospholipid syndrome.
AB  - OBJECTIVE: To investigate the prevalence of anti-C-reactive protein (CRP)
      autoantibodies in patients with systemic lupus erythematosus (SLE) and non-SLE
      patients with persistent antiphospholipid antibodies (aPL) and their association
      with clinical manifestations. METHODS: Sera of 137 patients with SLE, 127 with
      persistent aPL and 30 with idiopathic venous thromboembolic disease, were assayed
      for the presence of anti-CRP reactivity by ELISA. Associations of anti-CRP
      reactivity with clinical features, with other autoantibodies, and with serum
      concentrations of C3 and CRP were assessed. RESULTS: Antibodies against CRP were
      seen in 51% (n = 137) of patients with SLE and in 54% (n = 127) of patients with
      aPL. SLE patients with anti-CRP antibodies showed increased frequencies of anti
      dsDNA and aPL antibodies compared to those without anti-CRP (52% vs 26% and 68%
      vs 31%, respectively). Mean serum C3 levels were lower in the subgroup of
      patients with SLE positive for anti-CRP antibodies (79 +/- 25 vs 92 +/- 25 mg/dl;
      p = 0.004 ) and mean serum CRP levels were significantly higher (13 +/- 17 vs 5
      +/- 8 mg/l; p = 0.01 ). The frequency of nephritis was higher in SLE patients
      with anti-CRP antibodies, than in those without (27% vs 13%; p = 0.058). In
      patients with clinical and serological evidence of antiphospholipid syndrome
      (APS) the frequency of anti-CRP antibodies was significantly higher than in
      asymptomatic aPL carriers, in both SLE patients [85% (23 of 27) vs 59% (19 of
      32); p = 0.021] and non-SLE patients [76% (38 of 50) vs 19% (9 of 47); p <
      0.001]. Among patients with APS with or without SLE, 26 had arterial events, 31
      had venous events, 6 had combined arterial and venous events, and 14 had fetal
      loss. Mean titers of IgG anti-CRP (29 +/- 21, 30 +/- 19, 60 +/- 37, and 26 +/- 12
      AU/ml) and frequencies of anti-CRP antibodies (88%, 71%, 50%, and 71%) in these
      subgroups of patients were comparable. CONCLUSION: We confirmed the high
      prevalence of anti-CRP autoantibodies both in patients with SLE and in non-SLE
      and aPL-positive patients. We observed that the presence of these antibodies was
      associated with lupus nephritis and with clinical features of the APS in patients
      with lupus and non-lupus patients.

PMID- 17014015
TI  - Lack of clinical association with antibodies to ribosomal P proteins in Indian
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: We examined the prevalence and clinical association of the
      antiribosomal antibodies in our cohort of patients with systemic lupus
      erythematosus (SLE). METHODS: IgG antiribosomal P protein (anti-P) antibodies
      were detected in 202 consecutive patients with SLE and 212 age and sex matched
      healthy subjects by an in-house ELISA, using the 22-mer C-terminal peptide. In 13
      patients, IgG anti-P antibodies were also tested in paired cerebrospinal fluid
      (CSF) and sera samples. Clinical variables were compared in the antibody-positive
      and negative groups using appropriate statistical tests. RESULTS: Of the 202
      patients, 15 were male. Their median age was 30 years and the median disease
      duration was 36 months. Thirty-one patients (15.35%) were positive for IgG anti-P
      antibodies, of which 24 were also positive by Western blot. No association with
      SLE Disease Activity Index, nervous system disease, nephritis, hepatitis, skin
      disease, arthritis, and juvenile onset disease could be demonstrated. Levels of
      IgG anti-P antibodies in CSF were 100-fold less compared to levels in serum, and
      correlated well with the latter (r = 0.86; p < 0.01). CONCLUSION: The prevalence
      of IgG anti-P antibodies is similar in Indian and Caucasian patients with SLE. No
      association with specific organ involvement or age at onset could be
      demonstrated.

PMID- 17014016
TI  - Resistance to apoptosis in circulating alpha/beta and gamma/delta T lymphocytes
      from patients with systemic sclerosis.
AB  - OBJECTIVE: T cell activation plays a pivotal role in the immunopathogenesis of
      systemic sclerosis (SSc). Lymphocyte processes are tightly controlled by
      molecules activating either proliferation or programmed cell death (apoptosis).
      We investigated whether an imbalance in apoptotic function, increasing the
      survival rate of autoreactive cells, may lead to persistent autoreactive
      phenomena. METHODS: We studied peripheral a/b and g/d T lymphocytes of 22
      patients with SSc and 22 healthy controls for their spontaneous and stimulated
      (phytohemagglutinin, dexamethasone) apoptotic rate and surface phenotype
      including expression of Fas (CD95) and Bcl-2, determined by flow cytometry. sFas
      and sFas ligand in sera and supernatants were measured by ELISA. Caspase-3
      activation in response to agonistic anti-Fas Mab treatment was assessed. RESULTS:
      Lymphocytes of SSc patients showed a significant decrease in the percentage of
      apoptotic cells over time, in both unstimulated and stimulated cultures, compared
      to controls. We observed no difference between patients and controls, in
      stimulated or unstimulated cells, in the phenotypic expression of apoptotic
      cells, including surface Fas. SSc T cells were less susceptible to undergoing
      apoptosis after anti-Fas stimulation. We observed a significant decrease of
      apoptotic cells from stimulated culture of isolated SSc g/d T cells. Serum levels
      of sFas in SSc patients were significantly higher compared to controls. Similar
      data were obtained in the supernatants of stimulated and unstimulated cultures.
      By contrast, sFas ligand was always reduced. Bcl-2 expression in SSc was
      significantly elevated. A significant decrease in caspase-3 activity was detected
      in SSc patients after treatment by agonistic anti-Fas antibody. CONCLUSION:
      Resistance to apoptosis is present in a/b and g/d T cell lymphocyte subsets of
      patients with SSc, and several pathways seem to be connected in this setting.

PMID- 17014017
TI  - High prevalence of thyroid autoimmunity and hypothyroidism in patients with
      psoriatic arthritis.
AB  - OBJECTIVE: To evaluate the prevalence of thyroid disorders in a group of patients
      with psoriatic arthritis (PsA). METHODS: A complete thyroid investigation was
      carried out in 80 patients with PsA, in gender- and age-matched subjects (1:5)
      drawn from the general population (controls), and in 112 patients with rheumatoid
      arthrtitis (RA) with similar iodine intake. RESULTS: Anti-thyroid peroxidase
      antibodies (AbTPO), a hypoechoic thyroid, and subclinical hypothyroidism were
      significantly more frequent in women with PsA than in control women, and their
      frequency was similar to that in patients with RA (positive AbTPO titer 28%, 12%,
      and 31%; hypoechoic thyroid 31%, 16%, and 36%; subclinical hypothyroidism 25%,
      8%, and 12%, respectively). Among men, positive AbTPO titers and a hypoechoic
      thyroid were found more frequently in the patients with PsA and RA than in
      controls (positive AbTPO titer 14%, 5%, and 2%; hypoechoic thyroid 16%, 10%, and
      3%, respectively). All patients with PsA with subclinical hypothyroidism had
      polyarticular involvement (p </= 0.05) and a longer disease duration (years 19 +/
      15 vs 11 +/- 8, p = 0.03) than patients with euthyroid PsA. The prevalence of
      subclinical hyperthyroidism, thyroid nodules, and thyroid enlargement was not
      significantly different among the 3 groups. CONCLUSION: Our results demonstrate a
      significantly higher prevalence of thyroid autoimmunity (positive AbTPO,
      hyoechoic thyroid) findings in men and women with PsA and of subclinical
      hypothyroidism in women with PsA than in the general population. Therefore,
      thyroid function tests, an AbTPO assay, and thyroid ultrasound should be
      performed as part of the clinical evaluation, particularly in women with PsA.

PMID- 17014018
TI  - Effects of a combination treatment of an intensive rehabilitation program and
      etanercept in patients with ankylosing spondylitis: a pilot study.
AB  - OBJECTIVE: To determine the effects of a combination treatment including
      rehabilitation and etanercept versus rehabilitation only, on function,
      disability, and quality of life in a group of patients with active ankylosing
      spondylitis (AS). METHODS: Nineteen patients with AS consecutively admitted to a
      rehabilitation inpatient clinic were enrolled. Patients first participated in an
      intensive rehabilitation program and after a 6-month interval started etanercept
      therapy. After 3 weeks, they started a combination of rehabilitation and
      etanercept. The primary outcome measure was an improvement of the Bath Ankylosing
      Spondylitis Functional Index (BASFI) defined as the difference (Delta) between
      the 2 measurements (beginning and end). The difference between the 2 measurements
      for the first rehabilitation program was expressed as Delta1 and for the second
      as Delta2; the comparison between Delta1 and Delta2 for each outcome measure was
      taken into account. Secondary outcome measures included an improvement in the
      Revised Leeds Disability Questionnaire (LDQ), anthropometric measures, EuroQol
      (EQ-5Dvas), and the 6 minute walking test (6-MWT). RESULTS: A statistically
      significant improvement was observed both for BASFI (Delta1 = -0.71 +/- 0.23;
      Delta2 = -1.19 +/- 0.36, p < 0.001) and for LDQ (Delta1 = -0.28 +/- 0.08; Delta2
      = -0.46 +/- 0.17, p = 0.001). All anthropometric measures as well as 6-MWT were
      statistically improved. Finally, EQ5Dvas showed a statistically significant
      difference (Delta1 = 6.63 +/- 2.81; Delta2 = 20.26 +/- 4.89, p < 0.001). No
      adverse effects were seen during treatment with etanercept. CONCLUSION: This
      combination treatment seems to improve function, disability, and quality of life
      in patients with active AS.

PMID- 17014019
TI  - The management of gout at an academic healthcare center in Beijing: a physician
      survey.
AB  - OBJECTIVE: Gout is a less commonly diagnosed rheumatic disease in China compared
      with Western countries, but its prevalence appears to be climbing. It is not
      known how Chinese physicians diagnose and treat their patients with gout, so we
      evaluated physician management of gout at a major academic healthcare center in
      Beijing, and investigated factors associated with better decision-making.
      METHODS: A 13-question anonymous survey was distributed and collected at a
      medical grand rounds and then at a rheumatology grand rounds at a major teaching
      hospital in Beijing. Physician demographic data including educational background,
      work experience, job titles, specialty or subspecialties, gout patient volume
      seen in a year, and continuing medical education (CME) in gout were also
      collected in the survey. Data were analyzed by multivariate regression models to
      identify factors associated with appropriate answers. RESULTS: Twenty-seven
      residents and general internists, 26 rheumatologists and fellows, and 28
      physicians and fellows of other medical subspecialties from the Department of
      Medicine including visiting physicians responded to the survey. Among
      respondents, 78% think it is important for a definitive diagnosis of gout, but
      few actually perform aspiration of the affected joint fluid. Eighty-four percent
      report that they often follow the serum urate level of their patients with
      diagnosed gout. When treating acute gout in otherwise healthy patients, most
      physicians (77%) prefer oral colchicine, and in patients with renal impairment,
      about half of them (48%) choose corticosteroids or corticotropin as their first
      treatment. For longterm urate-lowering therapy, most physicians (87%) described a
      variety of indications that we consider less appropriate. They (86%) tend to
      initiate it early (< 2 weeks) after acute flares. When urate-lowering therapy is
      used, 80% of physicians sustain it less than 5 years. Further, only 12% of
      physicians use antiinflammatory prophylaxis during the initiation of urate
      lowering treatment, and only 5% maintain it for an appropriate period of time.
      Logistic regression analysis of physician demographic data, educational
      background, and work experience found no consistent independent factors
      associated with better decision-making, other than CME, that were associated with
      establishing the definite diagnosis correctly. Specifically, the number of gout
      patients seen by physicians was not related to better decision-making.
      CONCLUSION: The physicians' reported management of gout at this major academic
      healthcare center in Beijing was often inconsistent with current evidence. High
      quality CME is required to improve Chinese physician management of gout.

PMID- 17014020
TI  - A survey of current evaluation and treatment of gout.
AB  - OBJECTIVE: To record diagnostic and treatment approaches to gouty arthritis among
      US rheumatologists. METHODS: Questionnaires were faxed to 2500 US
      rheumatologists. RESULTS: Responses were received from 518 rheumatologists.
      Respondents reported performing crystal analysis 80% of the time for new
      suspected gout; 64% use combination therapy for acute gout; nonsteroidal
      antiinflammatory drugs alone are used in only 27%. Urate-lowering drugs (ULD) are
      given to most patients. ULD treatment is given occasionally to patients with
      asymptomatic hyperuricemia (4%) but most frequently to patients after 2 (59%) or
      3 (34%) attacks. ULD are given with the aim of achieving a serum urate (SU) level
      of 6 mg/dl. CONCLUSION: Combination antiinflammatory agents are used frequently
      for acute gout despite absence of evidence in the literature to support this
      practice. There seems to be consensus regarding the necessity of lowering SU to <
      6 mg/dl. Approaches vary widely, supporting the need for longterm prospective,
      placebo controlled studies to provide more evidence-based guidance.

PMID- 17014021
TI  - Preference for hip protectors among older adults at high risk for osteoporotic
      fractures.
AB  - OBJECTIVE: To determine older adults' treatment preferences for osteoporosis
      comparing bisphosphonates and hip protectors. METHODS: Subjects at high risk for
      an osteoporotic hip fracture completed a discrete choice questionnaire to
      determine preferences for hip protectors versus oral weekly bisphosphonates.
      Simulations, based on respondents' values for type of treatment and absolute
      reduction in risk of hip fractures over 5 years, were performed to predict
      treatment choices. RESULTS: Seventy-six patients participated in this study (92%
      participation rate). At the time of the study 57% of the participants were
      currently using bisphosphonates; none had ever heard of a hip protector. In the
      base-case scenario, in which both options were described as being equally
      effective, 9% preferred hip protectors, 88% weekly oral bisphosphonates, and 3%
      refused all options. When hip protectors were described as being more effective
      than bisphosphonates, 26% preferred hip protectors, 71% weekly oral
      bisphosphonates, and 3% continued to refuse all options. Preference for hip
      protectors was stronger among participants not currently using bisphosphonates
      (36% vs 19%, p = 0.08), as well as among subjects preferring to avoid taking
      prescription drugs for most health problems (44% vs 12%, p = 0.002). CONCLUSION:
      When presented with tradeoffs between hip protectors and bisphosphonates, the
      majority of community-dwelling older adults at high risk for fracture prefer the
      latter. Of note, however, many of the participants in this study were current
      bisphosphonate users. Future trials and education programs should consider
      targeting respondents preferring to manage health problems using nonpharmacologic
      treatment approaches since, based on the results of this study, adherence and
      proper use of hip protectors is expected to be higher among these patients.

PMID- 17014022
TI  - Lessons learned combining N-of-1 trials to assess fibromyalgia therapies.
AB  - OBJECTIVE: Applying population research to individual treatment requires
      understanding the connections between patient-specific characteristics,
      population-based studies, and treatment responses. Conducting practice-based
      research using individual-focused (N-of-1) trials may aid this process. We
      combined N-of-1 trials to compare fibromyalgia therapies and to assess the
      feasibility and outcomes of this approach for practice-based effectiveness
      research. METHODS: Community- and center-based rheumatologists enrolled patients
      with fibromyalgia syndrome in randomized, double-blind, multi-crossover, N-of-1
      trials comparing amitriptyline and the combination amitriptyline and fluoxetine.
      Fibromyalgia Impact Questionnaire outcomes were used for the individuals'
      treatment and combined across patients for sample-based analyses. Outcomes were
      compared with results from more standard trial designs. RESULTS: Eight
      rheumatologists enrolled 58 patients in N-of-1 trials. Most physicians and
      patients had not previously participated in clinical trials. Using several
      analytic methods, the pooled results showed a better outcome score (mean
      difference: -6.1 +/- 2.0 to -8.0 +/- 3.7 points) in patients taking combination
      therapy. These population results are similar to published outcomes from a more
      traditional crossover trial. Neither practice type nor patient characteristics
      were significantly associated with the observed treatment-effect variation. Most
      participants, irrespective of selected treatment, felt their individual N-of-1
      trials were helpful. CONCLUSION: Implementation of the combined N-of-1
      methodology is feasible in rheumatology practices and results confirm greater
      fibromyalgia improvement with combination therapy. This research approach
      broadens participation, although our trials' specifics likely influenced
      enrollment eligibility. In addition to individual benefits, combining N-of-1
      trial data provides population research benefits. This patient-focused approach
      should be further explored to bridge research and practice.

PMID- 17014023
TI  - Cyclophosphamide treatment of primary angiitis of the central nervous system in
      children: report of 2 cases.
AB  - Primary angiitis of the central nervous system (PACNS) is a rare, idiopathic
      vasculitis diagnosed most frequently in adults. We describe 2 children presenting
      with hemiplegia from PACNS treated with cyclophosphamide. Diagnosis in one child
      was based on abnormal angiography. Oral, but not intravenous (IV),
      cyclophosphamide was effective in preventing progressive weakness. The second
      child had unremarkable angiography, but brain biopsy revealed vasculitis; IV
      cyclophosphamide prevented further weakness. Both cases highlight the importance
      of early diagnosis and treatment.

PMID- 17014024
TI  - Interleukin 1 receptor antagonist to treat cytophagic histiocytic panniculitis
      with secondary hemophagocytic lymphohistiocytosis.
AB  - Cytophagic histiocytic panniculitis (CHP) is a rare, usually fatal disease of
      childhood; it typically presents with daily high spiking fevers and severe
      panniculitis. Hemophagocytosis from macrophage activation during a cytokine storm
      can result in pancytopenia and disseminated intravascular coagulopathy. We
      describe a 14-year-old girl with long-standing CHP who developed severe
      hemophagocytic lymphohistiocytosis, which responded to treatment with a
      combination of high dose corticosteroids, cyclosporine, and the interleukin 1
      receptor antagonist, anakinra.

PMID- 17014025
TI  - Ehlers-Danlos syndrome type IV in a young man.
AB  - We describe a 19-year-old male, with a family history of both systemic lupus
      erythematosus and Marfan syndrome, who had a history of bruising easily and skin
      lesions since childhood. He had a spontaneous colonic perforation at the age of
      16 years, followed 3 years later by sudden development of bilateral renal
      infarctions and hypertension, which on angiography were found to be due to
      dissection of both renal arteries. Transient elevations of 3 types of
      antiphospholipid antibodies (aPL) were detected. Skin biopsy showed typical
      elastosis perforans serpiginosa. The history together with the generalized
      connective tissue phenotype, histology, and angiographic features combined to
      establish a diagnosis of vascular Ehlers-Danlos syndrome, type IV; the body
      habitus resembled the phenotypically-related condition of Marfan syndrome. The
      coincidental finding of transient aPL elevations combined to make this a
      difficult diagnostic and clinical management problem.

PMID- 17014026
TI  - Hypopyon uveitis.

PMID- 17014027
TI  - Bullous pemphigoid in a patient with systemic sclerosis (scleroderma).

PMID- 17014028
TI  - Hypothyroidism and antithyroglobulin and antithyroperoxidase antibodies in the
      pathogenesis of autoimmune associated congenital heart block.

PMID- 17014029
TI  - Intestinal flora and psoriatic arthritis.

PMID- 17014030
TI  - An alternative vascular access technique for  haemodialysis; the loop mid-thigh
      graft.

PMID- 17014031
TI  - Internal jugular tunnelled dialysis catheters: a  method permitting repeated
      surgical insertions.

PMID- 17014032
TI  - Minimising scalpel handling.

PMID- 17014033
TI  - A new way of using a collar and cuff sling.

PMID- 17014034
TI  - Treatment of gastric cancer.

PMID- 17014035
TI  - Treatment of gastric cancer.

PMID- 17014036
TI  - Treatment of gastric cancer.

PMID- 17014037
TI  - Treatment of gastric cancer.

PMID- 17014038
TI  - Treatment of gastric cancer.

PMID- 17014039
TI  - Condom use and the risk of HPV infection.

PMID- 17014040
TI  - Homocysteine lowering and cognitive performance.

PMID- 17014041
TI  - Homocysteine lowering and cognitive performance.

PMID- 17014043
TI  - Retinol-binding protein 4 and insulin resistance.

PMID- 17014044
TI  - Retinol-binding protein 4 and insulin resistance.

PMID- 17014045
TI  - Molecular mechanisms in melanoma.

PMID- 17014046
TI  - Molecular mechanisms in melanoma.

PMID- 17014047
TI  - The choice: a longer life or more stuff.

PMID- 17014048
TI  - House passes abortion bill on minors.

PMID- 17014049
TI  - When scarcity leads to madness.

PMID- 17014050
TI  - Lung patients see a new era of transplants.

PMID- 17014051
TI  - Routine testing for the AIDS virus.

PMID- 17014052
TI  - Coffee does not increase risk of developing CAD.
AB  - There is no evidence that coffee consumption increases the likelihood that
      someone will develop heart disease.

PMID- 17014053
TI  - Cholesterol, Alzheimer's Disease and Statins. Proceedings of the 5th Symposium on
      Aging and Aging Disorders, Stockholm, Sweden, 14-15 April 2005.

PMID- 17014054
TI  - Proceedings of the 3rd International Conference on Vaccines for Enteric Diseases,
      Montego Bay, Jamaica, 28-30 April 2004.

PMID- 17014055
TI  - Best practices for retaining your 'sages'--nursing staff over age 50.

PMID- 17014056
TI  - [A new weapon against beta-3 lactamases?].

PMID- 17014057
TI  - Studies of the genus Culex linnaeus in Florida. III. Redescription of the fourth
      stage larva of Culex salinarius Coquillett and comparison with that of Cx.
      nigripalpus Theobald.
AB  - The larva of Culex salinarius is completely described and illustrated, except for
      the mouth parts, and compared with morphologically similar larva of Cx.
      nigripalpus. At least 8 characters have been found to separate larvae of the two
      species of which 7 give 90% or higher divergence while the remaining character
      gives 87% separation.

PMID- 17014058
TI  - How reliable is the humeral pale spot for identification of cryptic species of
      the Minimus Complex?
AB  - The Anopheles minimus Complex Theobald (Diptera: Culicidae) is composed of the 3
      sibling species A, C, and E. The malaria vectors An. minimus A and C are
      distributed over the Southeast Asian region, whereas species E is restricted to
      the Ryukyu Japanese Islands. Because species A and C can be sympatric and present
      specific behaviors and have a role in malaria transmission, it is important to
      differentiate them. The literature mentioned the presence of a presector pale
      spot on the wing costa of An. minimus A, whereas species C may exhibit both
      presector and humeral pale spots. However, the reliability of their diagnostic
      power has not been established over large temporal and geographic surveys. From
      the analyses of 9 populations throughout Southeast Asia, including published data
      and field populations from 2 sites in Thailand, we showed that the wing patterns
      present spatial and temporal variations that make these two morphological
      characters unreliable for the precise identification of An. minimus A and C.
      Therefore, molecular identification remains the most efficient method to obtain
      an unambiguous differentiation of these 2 species. Correct species identification
      is essential and mandatory for any relevant study on the Minimus Complex and for
      the application of successful control strategies.

PMID- 17014059
TI  - Population genetic structure of Anopheles maculatus in Thailand.
AB  - Anopheles (Cellia) maculatus Theobald is a major malaria vector in southern
      Thailand and peninsular Malaysia, and previous population genetic studies
      suggested that mountain ranges act as barriers to gene flow. In this study, we
      examine the genetic variance among 12 collections of natural populations in
      southern Thailand by analyzing 7 microsatellite loci. Based on analysis of
      molecular variance (AMOVA), three geographic populations of An. maculatus are
      suggested. The southern population exists in western Thailand north of 12 degrees
      north latitude. Mosquitoes to the south fall into two genetic populations: 1) the
      middle southern collections located on the west side of the Phuket mountain range
      between 8 degrees and 10 degrees north latitude, and 2) the southern collections
      located on the east of the Phuket mountain range located between approximately
      6.5 degrees and 11.5 degrees north latitude. AMOVA revealed significant genetic
      differentiation between northern and middle southern and southern populations.
      The middle southern population was moderately differentiated from the southern
      population. Furthermore, gene flow was restricted between proximal collections
      located on different sides of the Phuket mountain range. Collections separated by
      50 km exhibited restriction of gene flow when separated by geographic barriers,
      whereas greater gene flow was evident among collections 650 km apart but without
      geographic barriers.

PMID- 17014061
TI  - [Image of the week. Pneumothorax in a patient with pulmonary tuberculosis].

PMID- 17014060
TI  - Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body
      composition in children and adolescents infected with human immunodeficiency
      virus.
AB  - OBJECTIVE: To evaluate the effects of protease inhibitors (PIs) as antiretroviral
      therapy in comparison with other antiretroviral (non-PI) medications on glucose
      tolerance, lipid metabolism, and body fat distribution in human immunodeficiency
      virus (HIV)-infected young patients. METHODS: We conducted a cross-sectional
      clinical study in an outpatient HIV clinic. The study population consisted of 21
      patients (15 female and 6 male) who had had at least 6 months of antiretroviral
      treatment. The mean age of the patients was 11.9 years (range, 6 to 16.5).
      RESULTS: Fifteen patients treated with PIs and 6 patients treated with non-PIs
      were enrolled in the study. We found no significant differences in the lipid
      panel and insulin resistance, as determined by using the Quantitative Insulin
      Sensitivity Check Index formula, in the PI group in comparison with the non-PI
      group. Lipodystrophy was observed in 47% (7 of 15) of the PI group and 33% (2 of
      6) of the non-PI group (P = 0.66). In the presence of lipodystrophy, serum
      triglyceride levels were higher in the PI group than in the non-PI group (P =
      0.046). No such difference was found between the treatment groups when no
      lipodystrophy was present. There was no significant difference in insulin
      resistance between the treatment groups in the presence or absence of
      lipodystrophy. CONCLUSION: Our study found the presence of lipodystrophy in HIV
      infected young patients regardless of whether they were taking PIs or not. In the
      patients who had lipodystrophy, those treated with PIs had higher serum
      triglyceride levels than those not treated with PIs.

PMID- 17014062
TI  - Rituximab for rheumatoid arthritis.
AB  - (1) Rituximab (RTX), a monoclonal antibody, selectively targets CD20+ B-cells
      that are implicated in the pathogenesis of rheumatoid arthritis (RA). (2) The use
      of RTX with methotrexate (MTX) results in statistically significant clinical
      improvements among RA patients who have an inadequate response to standard
      therapies, when compared to the use of MTX alone. (3) The optimal dose, duration
      of treatment or retreatment, long-term efficacy and safety, and placement of RTX
      in RA treatment algorithms need to be further investigated. (4) Health Canada has
      approved the combination of RTX with MTX for use in adult patients with moderate
      to severe active RA, who have had an inadequate response or intolerance to >1
      tumour necrosis factor (TNF) inhibitor therapies.

PMID- 17014063
TI  - Transient elastography (FibroScan) for non-invasive assessment of liver fibrosis.
AB  - (1) Liver fibrosis is associated with significant morbidity and mortality. The
      major cause is hepatitis C, which affects 240,000 Canadians. (2) Assessing the
      degree of liver fibrosis is critical to its management. Liver biopsy, an invasive
      procedure, is considered to be the diagnostic gold standard. (3) FibroScan is a
      rapid, non-invasive technology that uses low frequency vibration and ultrasound
      to assess the stiffness of liver tissue. (4) The diagnostic performance of
      FibroScan is good for identifying severe fibrosis or cirrhosis, but it is less
      accurate for milder presentations. (5) FibroScan is a promising technology, but
      large multi-centre trials comparing a range of emerging non-invasive fibrosis
      staging technologies are required.

PMID- 17014065
TI  - Unwise and unnecessary: statutory caps on non-economic damages in medical
      malpractice cases and the appellate review alternative.

PMID- 17014064
TI  - New York's immediate need for a psychotherapist-patient privilege encompassing
      psychiatrists, psychologists, and social workers.

PMID- 17014066
TI  - [Definitions and prevention of cardiorespiratory arrest in children].
AB  - In cardiopulmonary resuscitation ages are divided in neonates (in the inmediate
      period after the birth), infant (from birth to 12 months) and child (from 12
      months to puberty). Respiratory arrest is defined by the absence of spontaneous
      respiration (apnea) or a severe respiratory insufficiency (agonal gasping) that
      require respiratory assistance. Cardiac arrest is defined as the absence of
      central arterial pulse or signs of circulation (movement, cough or normal
      breathing) or the presence of a central pulse less than 60 lpm in a child who
      does not respond, not breath and with poor perfusion. After resuscitation the
      return of spontaneous circulation is defined as the recuperation of central
      arterial pulse or signs of circulation in a child with previous cardiorespiratory
      arrest. It is maintained when the duration is longer than 20 minutes. Injuries,
      sudden infant death syndrome, and respiratory diseases are the most frequent
      etiologies of cardiorrespiratory arrest in children. The prevention and the
      formation of citizens in basic cardiopulmonary resuscitation are the most
      effective measures to reduce the mortality of cardiorespiratory arrest in
      children.

PMID- 17014067
TI  - [Recognition of the child at risk of cardiopulmonary arrest].
AB  - Early treatment is a major factor to improve the outcome of children at risk of
      cardiopulmonary arrest. That's why it is essential to recognize as soon as
      possible clinical signs that indicate a respiratory and/or circulatory
      dysfunction. Immediate systematic assessment and re-assessment of oxygenation,
      ventilation and organ perfusion status is one of the keys in the prevention of
      cardiorespiratory arrest in children. Health care staff must assure that a child
      with signs of acute respiratory and/or circulatory dysfunction is under constant
      surveillance by a person with ability to interpret signs, identify problems and
      to initiate emergency treatment, if needed. Respiratory assessment must include
      respiratory rate, signs of mechanical respiratory failure (nasal flaring,
      respiratory noises, paradoxical breathing, prolonged expiration) as well as skin
      mucous colour. Cardiocirculatory failure assessment includes heart rate, blood
      pressure, peripheral perfusion (capillary refill time and temperature gradient),
      level of consciousness and urinary output. In a child with impending signs of
      cardio-respiratory failure, the priority is to warrant adequate ventilation and
      oxygenation. If, despite this treatment, there is no improvement in perfusion,
      treatment of circulatory failure with fluids and vasoactive drugs is necessary.

PMID- 17014068
TI  - WTC effects deserve the world's attention.

PMID- 17014069
TI  - Decoding the electrical heart. How to care for patients with pacemakers & AICDs.

PMID- 17014071
TI  - Is prophylactic anti-incontinence surgery beneficial at the time of vaginal
      prolapse repair?

PMID- 17014070
TI  - Safety and tolerability of tolterodine for the treatment of overactive bladder in
      men with bladder outlet obstruction.

PMID- 17014072
TI  - Identifying the optimal procedure for the surgical repair of female stress
      urinary incontinence.

PMID- 17014073
TI  - Catalytic mechanism of S-ribosylhomocysteinase: ionization state of active-site
      residues.
AB  - S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in
      S-ribosylhomocysteine (SRH) to produce homocysteine (Hcys) and 4,5-dihydroxy-2,3
      pentanedione (DPD), the precursor of type II bacterial autoinducer (AI-2). The
      proposed catalytic mechanism involves two consecutive ribose carbonyl migration
      steps via an intramolecular redox reaction and a subsequent beta-elimination
      step, all catalyzed by a divalent metal ion (e.g., Fe(2+) or Co(2+)) and two
      general acids/bases in the active site. Absorption and EPR spectroscopic studies
      were performed with both wild-type and various mutant forms of LuxS under a wide
      range of pH conditions. The studies revealed a pK(a) of 10.4 for the metal-bound
      water. The pK(a) value of Cys-83 was determined to be <6 by (13)C-(1)H HSQC NMR
      experiments with [3-(13)C]cysteine-labeled Zn(2+)-substituted Escherichia coli
      LuxS. The active form of LuxS contains a metal-bound water and a thiolate ion at
      Cys-83, consistent with the proposed roles of the metal ion (Lewis acid) and Cys
      83 (general acid/base) during catalysis. Finally, an invariant Arg-39 in the
      active site was demonstrated to be at least partially responsible for stabilizing
      the thiolate anion of Cys-83.

PMID- 17014074
TI  - Time-resolved fluorescence studies of heterotropic ligand binding to cytochrome
      P450 3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) is a major enzymatic determinant of drug and
      xenobiotic metabolism that demonstrates remarkable substrate diversity and
      complex kinetic properties. The complex kinetics may result, in some cases, from
      multiple binding of ligands within the large active site or from an effector
      molecule acting at a distal allosteric site. Here, the fluorescent probe TNS (2-p
      toluidinylnaphthalene-6-sulfonic acid) was characterized as an active site
      fluorescent ligand. UV-vis difference spectroscopy revealed a TNS-induced low
      spin heme absorbance spectrum with an apparent K(d) of 25.4 +/- 2 microM.
      Catalytic turnover using 7-benzyloxyquinoline (7-BQ) as a substrate demonstrated
      TNS-dependent inhibition with an IC(50) of 9.9 +/- 0.1 microM. These results
      suggest that TNS binds in the CYP3A4 active site. The steady-state fluorescence
      of TNS increased upon binding to CYP3A4, and fluorescence titrations yielded a
      K(d) of 22.8 +/- 1 microM. Time-resolved frequency-domain measurement of TNS
      fluorescence lifetimes indicates a testosterone (TST)-dependent decrease in the
      excited-state lifetime of TNS, concomitant with a decrease in the steady-state
      fluorescence intensity. In contrast, the substrate erythromycin (ERY) had no
      effect on TNS lifetime, while it decreased the steady-state fluorescence
      intensity. Together, the results suggest that TNS binds in the active site of
      CYP3A4, while the first equivalent of TST binds at a distant allosteric effector
      site. Furthermore, the results are the first to indicate that TST bound to the
      effector site can modulate the environment of the heterotropic ligand.

PMID- 17014076
TI  - Tandem repeat-like domain of "similar to prion protein" (StPrP) of Japanese
      pufferfish binds Cu(II) as effectively as the mammalian protein.
AB  - The main structural domains of prion proteins, in particular the N-terminal
      region containing characteristic amino acid repeats, are well conserved among
      different species, despite divergence in primary sequence. The repeat region
      seems to play an important role, as verified by pathogenicity only observed in
      organisms having repeats composed of eight residues. In this work three different
      peptides belonging to the tandem repeat region of StPrP-2 from the Japanese
      pufferfish Takifugu rubripes have been considered; the coordination modes and
      conformations of their complexes with Cu(II) have been investigated by using
      potentiometric titrations, spectroscopic data, and restrained molecular dynamics
      simulations. In all cases the histidine imidazole(s) provide the anchoring site
      for copper, with the further involvement of amide nitrogens depending on the
      peptide sequence and on pH. An increase in copper binding affinity has been
      observed going from the shortest peptide, corresponding to a single repeat and
      containing two histidines, to the longest one, encompassing three repeats with
      six histidines.

PMID- 17014075
TI  - Multiple levels of affinity-dependent DNA discrimination in Cre-LoxP
      recombination.
AB  - Cre recombinase residue Arg259 mediates a canonical bidentate hydrogen-bonded
      contact with Gua27 of its LoxP DNA substrate. Substituting Cyt8-Gua27 with the
      three other basepairs, to give LoxAT, LoxTA, and LoxGC, reduced Cre-mediated
      recombination in vitro, with the preference order of Gua27 > Ade27 approximately
      Thy27 >> Cyt27. While LoxAT and LoxTA exhibited 2.5-fold reduced affinity and 2.5
      5-fold slower reaction rates, LoxGC was a barely functional substrate. Its
      maximum level of turnover was 6-fold reduced over other substrates, and it
      exhibited 8.5-fold reduced Cre binding and 6.3-fold slower turnover rate. With
      LoxP, the rate-limiting step for recombination occurs after protein-DNA complex
      assembly but before completion of the first strand exchange to form the Holliday
      junction (HJ) intermediate. With the mutant substrates, it occurs after HJ
      formation. Using an increased DNA-binding E262Q/E266Q "CreQQ" variant, all four
      substrates react more readily, but with much less difference between them, and
      maintained the earlier rate-limiting step. The data indicate that Cre
      discriminates substrates through differences in (i) concentration dependence of
      active complex assembly, (ii) turnover rate, and (iii) maximum yield of product
      at saturation, all of which are functions of the Cre-DNA binding interaction.
      CreQQ suppression of Lox mutant defects implies that coupling between binding and
      turnover involves a change in Cre subunit DNA affinities during the
      "conformational switch" that occurs prior to the second strand exchange. These
      results provide an example of how a DNA-binding enzyme can exert specificity via
      affinity modulation of conformational transitions that occur along its reaction
      pathway.

PMID- 17014077
TI  - Structural studies of Apo NosL, an accessory protein of the nitrous oxide
      reductase system: insights from structural homology with MerB, a mercury
      resistance protein.
AB  - The formation of the unique catalytic tetranuclear copper cluster (Cu(Z)) of
      nitrous oxide reductase, N(2)OR, requires the coexpression of a multiprotein
      assembly apparatus encoded by the nosDFYL operon. NosL, one of the proteins
      encoded by this transcript, is a 20 kDa lipoprotein of the periplasm that has
      been shown to bind copper(I), although its function has yet to be detemined.
      Cu(I) EXAFS data collected on the holo protein demonstrated that features of the
      copper binding site are consistent with a role for this protein as a
      metallochaperone, a class of metal ion transporters involved in metal resistance,
      homeostasis, and metallocluster biosynthesis. To test this hypothesis and to gain
      insight into other potential functional roles for this protein in the N(2)OR
      system, the three-dimensional solution structure of apo NosL has been solved by
      solution NMR methods. The structure of apo NosL consists of two relatively
      independent homologous domains that adopt an unusual betabetaalphabeta topology.
      The fold of apo NosL displays structural homology to only one other protein,
      MerB, an organomercury lyase involved in bacterial mercury resistance (Di Lello
      et al. (2004) Biochemistry 43, 8322-32). The structural similarity between apo
      NosL and MerB, together with the absolute conservation of Met109 in all NosL
      sequences, indicates that this residue may be involved in copper ligation, and
      that the metal binding site is likely to be solvent-accessible and contiguous
      with a large binding cleft. The structural observations suggest that NosL is
      exceptionally adapted for a role in copper and/or sulfur delivery and possibly
      for metallochaperone function.

PMID- 17014078
TI  - Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B
      3 cells by 4-hydroxynonenal.
AB  - The Fas (apo/CD95) receptor which belongs to the TNF-alpha family is a
      transmembrane protein involved in the signaling for apoptosis through the
      extrinsic pathway. During this study, we have examined a correlation between
      intracellular levels of 4-HNE and expression of Fas in human lens epithelial (HLE
      B-3) cells. Our results show that in HLE B-3 cells, Fas is induced by 4-HNE in a
      concentration- and time-dependent manner, and it is accompanied by the activation
      of JNK, caspase 3, and the onset of apoptosis. Fas induction and activation of
      JNK are also observed in various tissues of mGsta4 null mice which have elevated
      levels of 4-HNE. Conversely, when 4-HNE is depleted in HLE B-3 cells by a
      transient transfection with hGSTA4, Fas expression is suppressed. However, upon
      the cessation of hGSTA4 expression in these transiently transfected cells, Fas
      and 4-HNE return to their basal levels. Fas-deficient transformed HLE B-3 cells
      stably transfected with hGSTA4 show remarkable resistance to apoptosis. Also, the
      wild-type HLE B-3 cells in which Fas is partially depleted by siRNA acquire
      resistance to 4-HNE-induced apoptosis, suggesting an at least partial role of Fas
      in 4-HNE-induced apoptosis in HLE B-3 cells. We also demonstrate that during 4
      HNE-induced apoptosis of HLE B-3 cells, Daxx is induced and it binds to Fas.
      Together, these results show an important role of 4-HNE in regulation of the
      expression and functions of Fas.

PMID- 17014079
TI  - 11-cis-Acyl-CoA:retinol O-acyltransferase activity in the primary culture of
      chicken Muller cells.
AB  - A novel retinoid cycle has recently been identified in the cone-dominated chicken
      retina, and this cone cycle accumulates 11-cis-retinyl esters upon light
      adaptation. The purpose of this study is to investigate how 11-cis-retinyl esters
      are formed in the retina. Primary cultures of chicken Muller cells and cell
      membrane were incubated with all-trans- or 11-cis-retinol to study retinyl ester
      synthesis. In Muller cells, esterification of 11-cis-retinol was four times
      greater than esterification of all-trans-retinol. In the presence of palmitoyl
      CoA and CRALBP, Muller cell membranes synthesized 11-cis-retinyl ester from 11
      cis-retinol at a rate which was 20-fold higher than that of all-trans-retinyl
      ester. In the absence of CRALBP, 11-cis-retinyl ester synthesis was greatly
      reduced (by 7-fold). In the absence of palmitoyl-CoA, retinyl ester synthesis was
      not observed. Muller cell membranes incubated with radiolabeled palmitoyl-CoA
      resulted in the transfer of the labeled acyl group to retinol. This acyl transfer
      was greatly reduced in the presence of progesterone, a known ARAT inhibitor. 11
      cis-ARAT activity remained unchanged when assayed in the presence of all-trans
      retinol, suggesting a distinct catalytic activity from that of all-trans-ARAT.
      Apparent kinetic rates for 11-cis-ARAT were 0.135 nmol min(-)(1) mg(-)(1)
      (V(max)) and 11.25 microM (K(M)) and for all-trans-ARAT were 0.0065 nmol min(
      )(1) mg(-)(1) (V(max)) and 28.88 microM (K(M)). Our data indicate that Muller
      cells in the chicken retina possess 11-cis-ARAT activity, thus providing an
      explanation for the accumulation of 11-cis-retinyl esters in the cone cycle.

PMID- 17014080
TI  - Biotin synthase mechanism: mutagenesis of the YNHNLD conserved motif.
AB  - Biotin synthase, a member of the "radical SAM" family, catalyzes the final step
      of the biotin biosynthetic pathway, namely, the insertion of a sulfur atom into
      dethiobiotin (DTB). The active form of the enzyme contains two iron-sulfur
      clusters, a [4Fe-4S](2+) cluster liganded by Cys-53, Cys-57, and Cys-60 and the S
      adenosylmethionine (AdoMet or SAM) cosubstrate and a [2Fe-2S](2+) cluster
      liganded by Cys-97, Cys-128, Cys-188, and Arg-260. Single-point mutation of each
      of these six conserved cysteines produced inactive variants. In this work,
      mutants of other highly conserved residues from the Y(150)NHNLD motif are
      described. They have properties similar to those of the wild-type enzyme with
      respect to their cluster content and characteristics. For all of them, the as
      isolated form, which contains an air-stable [2Fe-2S](2+) center, can additionally
      accommodate an air-sensitive [4Fe-4S](2+) center which is generated by incubation
      under anaerobic conditions with Fe(2+) and S(2-). Their spectroscopic properties
      are similar to those of the wild type. However, they are inactive, except the
      mutant H152A that exhibits a weak activity. We show that the mutants, inactive in
      producing biotin, are also unable to cleave AdoMet and to produce the
      deoxyadenosyl radical (AdoCH(2)(*)). In the case of H152A, a value of 5.5 +/- 0.4
      is found for the 5'-deoxyadenosine (AdoCH(3)):biotin ratio, much higher than the
      value of 2.8 +/- 0.3 usually observed with the wild type. This reveals a greater
      contribution of the abortive process in which the AdoCH(2)(*) radical is quenched
      by hydrogen atoms from the protein or from some components of the system. Thus,
      in this case, the coupling between the production of AdoCH(2)(*) and its reaction
      with the hydrogen at C-6 and C-9 of DTB is less efficient than that in the wild
      type, probably because of geometry's perturbation within the active site.

PMID- 17014082
TI  - Targeting DNA mismatches with rhodium intercalators functionalized with a cell
      penetrating peptide.
AB  - Cell-penetrating peptides are widely used to deliver cargo molecules into cells.
      Here we describe the synthesis, characterization, DNA binding, and cellular
      uptake studies of a series of metal-peptide conjugates containing oligoarginine
      as a cell-penetrating peptide. d-Octaarginine units are appended onto a rhodium
      intercalator containing the sterically expansive chrysenequinone diimine (chrysi)
      ligand to form Rh(chrysi)(phen)(bpy)(3+)-tethered oligoarginine conjugates, where
      the peptide is attached to the ancillary bpy ligand; some conjugates also include
      a fluorescein or thiazole orange tag. These complexes bind and with
      photoactivation selectively cleave DNA neighboring single-base mismatches. The
      presence of the oligoarginines is found to increase the nonspecific binding
      affinity of the complexes for both matched and mismatched DNA, but for these
      conjugates, photocleavage remains selective for the mismatched site, as assayed
      using both gel electrophoresis and mass spectrometry experiments. Significantly,
      the rhodium complex does not interfere with the delivery properties of the cell
      penetrating peptide. Confocal microscopy experiments show rapid nuclear
      localization of the metal-peptide conjugates containing the tethered fluorescein.
      Mass spectrometry experiments confirm the association of the rhodium with the
      HeLa cells. These results provide a strategy for targeting mismatch-selective
      metal complexes inside cell nuclei.

PMID- 17014081
TI  - Determination of the in vivo stoichiometry of tyrosyl radical per betabeta' in
      Saccharomyces cerevisiae ribonucleotide reductase.
AB  - The class I ribonucleotide reductases catalyze the conversion of nucleotides to
      deoxynucleotides and are composed of two subunits: R1 and R2. R1 contains the
      site for nucleotide reduction and the sites that control substrate specificity
      and the rate of reduction. R2 houses the essential diferric-tyrosyl radical
      (Y(*)) cofactor. In Saccharomyces cerevisiae, two R1s, alpha(n) and , have been
      identified, while R2 is a heterodimer (betabeta'). beta' cannot bind iron and
      generate the Y(*); consequently, the maximum amount of Y(*) per betabeta' is 1.
      To determine the cofactor stoichiometry in vivo, a FLAG-tagged beta ((FLAG)beta)
      was constructed and integrated into the genome of Y300 (MHY343). This strain
      facilitated the rapid isolation of endogenous levels of (FLAG)betabeta' by
      immunoaffinity chromatography, which was found to have 0.45 +/- 0.08
      Y(*)/(FLAG)betabeta' and a specific activity of 2.3 +/- 0.5 micromol min(-1) mg(
      1). (FLAG)betabeta' isolated from MMS-treated MHY343 cells or cells containing a
      deletion of the transcriptional repressor gene CRT1 also gave a
      Y(*)/(FLAG)betabeta' ratio of 0.5. To determine the Y(*)/betabeta' ratio without
      R2 isolation, whole cell EPR and quantitative Western blots of beta were
      performed using different strains and growth conditions. The wild-type (wt)
      strains gave a Y(*)/betabeta' ratio of 0.83-0.89. The same strains either treated
      with MMS or containing a crt1Delta gave ratios between 0.49 and 0.72. Nucleotide
      reduction assays and quantitative Western blots from the same strains provided an
      independent measure and confirmation of the Y(*)/betabeta' ratios. Thus, under
      normal growth conditions, the cell assembles stoichiometric amounts of Y(*) and
      modulation of Y(*) concentration is not involved in the regulation of RNR
      activity.

PMID- 17014083
TI  - Domain motions of the Mip protein from Legionella pneumophila.
AB  - The homodimeric 45.6 kDa (total mass) Mip protein, a virulence factor from
      Legionella pneumophila, was investigated with solution NMR spectroscopy and
      molecular dynamics (MD) simulations. Two Mip monomers are dimerized via an N
      terminal helix bundle that is connected via a long alpha-helix to a C-terminal
      FKBP domain in each subunit. More than 85% of the amino acids were identified in
      triple-resonance NMR spectra. (15)N relaxation analysis showed a bimodal
      distribution of R(1)/R(2) values, with the lower ratio in the N-terminal domain.
      Relaxation dispersion measurements confirmed that these reduced ratios did not
      originate from conformational exchange. Thus, two different correlation times
      (tau(c)) can be deduced, reflecting partly uncoupled motions of both domains.
      Relaxation data of a Mip(77)(-)(213) monomer mutant were similar to those
      observed in the dimer, corroborating that the FKBP domain, including part of the
      connecting helix, behaves as one dynamic entity. MD simulations (18 ns) of the
      Mip dimer also yielded two different correlation times for the two domains and
      thus confirm the independence of the domain motions. Principal component analysis
      of the dihedral space covariance matrix calculated from the MD trajectory
      suggests a flexible region in the long connecting helix that acts as a hinge
      between the two domains. Such motion provides a possible explanation of how Mip
      can bind to complex molecular components of the extracellular matrix and mediate
      alveolar damage and bacterial spread in the lung.

PMID- 17014084
TI  - Folding mechanism of a multiple independently-folding domain protein: double B
      domain of protein A.
AB  - The antibody binding properties of staphylococcal protein A (SpA) can be
      attributed to the presence of five highly homologous domains (E, D, A, B, and C).
      Although the folding of the B domain of protein A (BdpA) is well-characterized,
      the folding behavior of this domain in the context of full-length SpA in the cell
      remains unexplored. The sequence of the B domain is 89 and 91% identical to those
      of domains A and C, respectively. We have fused B domain sequences (BBdpA) as a
      close approximation of the A-B or B-C portion of SpA. Circular dichroism and
      fluorescence-detected denaturation curves of BBdpA are experimentally
      indistinguishable from those of BdpA. The rate constants for folding and
      unfolding from NMR line shape analysis for the single- and double-domain proteins
      are the same within experimental uncertainties (+/-20%). These results support
      the designation of SpA as a multiple independently-folding domain (MIFD) protein.
      We develop a mathematical model that describes the folding thermodynamics and
      kinetics of MIFD proteins. The model depicts MIFD protein folding and unfolding
      as a parallel network and explicitly calculates the flux through all parallel
      pathways. These fluxes are combined to give a complete description of the global
      thermodynamics and kinetics of the folding and unfolding of MIFD proteins. The
      global rates for complete folding and unfolding of a MIFD protein and those of
      the individual domains depend on the stability of the protein. We show that the
      global unfolding rate of a MIFD protein may be many orders of magnitude slower
      than that of the constituent domains.

PMID- 17014085
TI  - Secondary structure mapping of DnaK-bound protein fragments: chain helicity and
      local helix unwinding at the binding site.
AB  - Little is known about polypeptide conformation and folding in the presence of
      molecular chaperones participating in protein biosynthesis. In vitro studies on
      chaperone-substrate complexes have been mostly carried out with small peptide
      ligands. However, the technical challenges associated with either competing
      aggregation or spectroscopically unfavorable size and exchange rates have
      typically prevented analysis of larger substrates. Here, we report the high
      resolution secondary structure of relatively large N-terminal protein fragments
      bound to the substrate-binding domain of the cotranslationally active chaperone
      DnaK. The all-alpha-helical protein apomyoglobin (apoMb), bearing the ubiquitous
      globin fold, has been chosen as a model substrate. On the basis of NMR secondary
      chemical shift analysis, we identify, for the first time, weak helical content
      (similar to that found in the chemically unfolded full-length protein) for the
      assigned residues of the chaperone-bound chain away from the chaperone binding
      sites. In contrast, we found that the residues corresponding to the strongest
      specific binding site for DnaK, examined via a short 13-mer apoMb peptide
      fragment matching the binding site sequence, display highly reduced helical
      content in their chaperone-bound form. Given that the free state of the peptide
      is weakly helical in isolation, we conclude that the substrate residues
      corresponding to the chaperone binding site undergo helix unwinding upon
      chaperone binding.

PMID- 17014086
TI  - Pathway of ATP hydrolysis by monomeric kinesin Eg5.
AB  - Kinesin-5 family members including human Eg5/KSP contribute to the plus-end
      directed force necessary for the assembly and maintenance of the bipolar mitotic
      spindle. We have used monomeric Eg5-367 in the nucleotide-free state to evaluate
      the role of microtubules at each step in the ATPase cycle. The pre-steady-state
      kinetic results show that the microtubule-Eg5 complex binds MgATP tightly,
      followed by rapid ATP hydrolysis with a subsequent slow step that limits steady
      state turnover. We show that microtubules accelerate the kinetics of each step in
      the ATPase pathway, suggesting that microtubules amplify the nucleotide-dependent
      structural transitions required for force generation. The experimentally
      determined rate constants for phosphate product release and Eg5 detachment from
      the microtubule were similar, suggesting that these two steps are coupled with
      one occurring at the slow rate after ATP hydrolysis followed by the second step
      occurring more rapidly. The rate of this slow step correlates well with the
      steady-state k(cat), indicative that it is the rate-limiting step of the
      mechanism.

PMID- 17014087
TI  - Photophysical behavior and assignment of the low-energy chlorophyll states in the
      CP43 proximal antenna protein of higher plant photosystem II.
AB  - We have employed absorption, circular dichroism (CD), and persistent spectral
      hole-burning measurements at 1.7 K to study the photoconversion properties and
      exciton coupling of low-energy chlorophylls (Chls) in the CP43 proximal antenna
      light-harvesting subunit of photosystem II (PSII) isolated from spinach. These
      approximately 683 nm states act as traps for excitation energy in isolated CP43.
      They "bleach" at 683 nm upon illumination and photoconvert to a form absorbing in
      the range approximately 660-680 nm. We present new data that show the changes in
      the CD spectrum due to the photoconversion process. These changes occur in
      parallel with those in absorption, providing evidence that the feature undergoing
      the apparent bleach is a component of a weakly exciton-coupled system. From our
      photoconversion difference spectra, we assign four states in the Chl long
      wavelength region of CP43, two of which are the known trap states and are both
      highly localized on single Chls. The other two states are associated with weak
      exciton coupling (maximally approximately 50 cm(-)(1)) to one of these traps. We
      propose a mechanism for photoconversion that involves Chl-protein hydrogen
      bonding. New hole-burning data are presented that indicate this mechanism is
      distinct to that for narrow-band spectral hole burning in CP43. We discuss the
      photophysical behavior of the Chl trap states in isolated CP43 compared to their
      behavior in intact PSII preparations. The latter represent a more intact,
      physiological complex, and we find no clear evidence that they exhibit the
      photoconversion process reported here.

PMID- 17014088
TI  - Determination of the substrate specificities of N-acetyl-d
      glucosaminyltransferase.
AB  - Heparan sulfate plays a wide range of physiological and pathological roles.
      Heparan sulfate consists of glucosamine and glucuronic/iduronic acid repeating
      disaccharides with various sulfations. Synthesis of structurally defined heparan
      sulfate oligosaccharides remains a challenge. Access to nonsulfated and
      unepimerized heparan sulfate backbone structures represents an essential step
      toward de novo enzymatic synthesis of heparan sulfate. The nonsulfated,
      unepimerized backbone heparan sulfate is similar to the capsular polysaccharide
      from Escherichia coli strain K5. The biosynthesis of this capsular polysaccharide
      involves in N-acetylglucosaminyltransferase (KfiA) and d-glucuronyltransferase
      (KfiC). In this study, we report the characterization of purified KfiA. KfiA was
      expressed in a C-terminal six-His fusion protein in BL21 star cells coexpressing
      chaperone proteins GroEL and GroES. The recombinant KfiA was purified to
      homogeneity with a Ni-agarose column. The binding affinities of various UDP
      sugars for KfiA were determined using isothermal calorimetry titration,
      indicating that both the N-acetyl group and sugar type may be essential for donor
      substrates to bind KfiA. Kinetic analysis of KfiA toward different sizes of
      oligosaccharide revealed that KfiA is less sensitive to the size of the acceptor
      substrates. The results from this study open a new approach for the synthesis of
      the heparan sulfate backbone.

PMID- 17014089
TI  - Methylglyoxal is an intermediate in the biosynthesis of 6-deoxy-5-ketofructose-1
      phosphate: a precursor for aromatic amino acid biosynthesis in Methanocaldococcus
      jannaschii.
AB  - A biosynthetic pathway is proposed for creating 6-deoxy-5-ketofructose-1
      phosphate (DKFP), a precursor sugar for aromatic amino acid biosynthesis in
      Methanocaldococcus jannaschii. First, two possible routes were investigated to
      determine if a modified, established biosynthetic pathway could be responsible
      for generating 6-deoxyhexoses in M. jannaschii. Both the nucleoside diphosphate
      mannose pathway and a pathway involving nucleoside diphosphate derivatives of
      fructose-1-P, fructose-2-P, or fructose-1,6-bisP were tested and eliminated. The
      established pathways did not produce the expected intermediates nor did the
      anticipated enzymes have the predicted enzymatic activities. Because neither
      anticipated pathway could produce DKFP, M. jannaschii glucose-6-P metabolism was
      studied in detail to establish exactly how glucose-6-P is converted into DKFP.
      This detailed analysis showed that methylglyoxal and a fructose-1-P- or fructose
      1,6-bisP-derived dihydroxyacetone-P fragment are key intermediates in DKFP
      production. Glucose-6-P readily converts to fructose-6-P, which in turn converts
      to fructose-1,6-bisP. Fructose-6-P and fructose-1,6-bisP convert into
      glyceraldehyde-3-P (Ga-P-3), which converts into methylglyoxal by a 2,3
      elimination of phosphate. The MJ1585-derived enzyme catalyzes the condensation of
      methylglyoxal with a dihydroxyacetone-P fragment, which is derived from fructose
      1-P and/or fructose-1,6-bisP, generating DKFP. The elimination of phosphate from
      Ga-P-3 proceeds by both enzymatic and chemical routes in cell extracts, producing
      sufficient concentrations of methylglyoxal to support the reaction. This work is
      the first report of methylglyoxal functioning in central metabolism.

PMID- 17014090
TI  - Characterization of a naphthalene dioxygenase endowed with an exceptionally broad
      substrate specificity toward polycyclic aromatic hydrocarbons.
AB  - In Sphingomonas CHY-1, a single ring-hydroxylating dioxygenase is responsible for
      the initial attack of a range of polycyclic aromatic hydrocarbons (PAHs) composed
      of up to five rings. The components of this enzyme were separately purified and
      characterized. The oxygenase component (ht-PhnI) was shown to contain one Rieske
      type [2Fe-2S] cluster and one mononuclear Fe center per alpha subunit, based on
      EPR measurements and iron assay. Steady-state kinetic measurements revealed that
      the enzyme had a relatively low apparent Michaelis constant for naphthalene (K(m)
      = 0.92 +/- 0.15 microM) and an apparent specificity constant of 2.0 +/- 0.3 mM(
      )(1) s(-)(1). Naphthalene was converted to the corresponding 1,2-dihydrodiol with
      stoichiometric oxidation of NADH. On the other hand, the oxidation of eight other
      PAHs occurred at slower rates and with coupling efficiencies that decreased with
      the enzyme reaction rate. Uncoupling was associated with hydrogen peroxide
      formation, which is potentially deleterious to cells and might inhibit PAH
      degradation. In single turnover reactions, ht-PhnI alone catalyzed PAH
      hydroxylation at a faster rate in the presence of organic solvent, suggesting
      that the transfer of substrate to the active site is a limiting factor. The four
      ring PAHs chrysene and benz[a]anthracene were subjected to a double ring
      dihydroxylation, giving rise to the formation of a significant proportion of bis
      cis-dihydrodiols. In addition, the dihydroxylation of benz[a]anthracene yielded
      three dihydrodiols, the enzyme showing a preference for carbons in positions 1,2
      and 10,11. This is the first characterization of a dioxygenase able to
      dihydroxylate PAHs made up of four and five rings.

PMID- 17014092
TI  - Modulating fluorescence resonance energy transfer in conjugated liposomes.
AB  - We report here a novel system where the rate of energy transfer is based on
      changes in the spectral overlap between the emission of the donor and the
      absorption of the acceptor (J) as well as changes in the quantum yield of the
      acceptor. We use the fluorophore dansyl as the donor and polydiacetylene (PDA) as
      the acceptor to demonstrate the modulation of FRET through conformationally
      induced changes in the PDA absorption spectrum following thermal treatment that
      converts the PDA backbone of the liposome from the blue form to the red form.
      Energy transfer was found to be significantly more efficient from dansyl to the
      red-form PDA. These findings support the basis of a new sensing platform that
      utilizes J-modulated FRET as an actuating mechanism.

PMID- 17014093
TI  - Microfluidic assembly of homogeneous and Janus colloid-filled hydrogel granules.
AB  - The microfluidic assembly of colloid-filled hydrogel granules of varying shape
      and composition is described. First, drops are formed by shearing a concentrated
      colloidal microsphere-acrylamide suspension in a continuous oil phase using a
      sheath-flow device. Both homogeneous and Janus (hemispherically distinct) spheres
      and disks are produced by confining the assembled drops in microchannels of
      varying geometry. Next, photopolymerization is carried out shortly after drop
      breakup to preserve their morphology. Representative wet and dried granules are
      characterized using fluorescence and scanning electron microscopy, respectively.
      Our approach offers a facile route for assembling colloid-filled hydrogel
      granules with controlled shape and composition.

PMID- 17014094
TI  - Mineralization of monodispersed CdS nanoparticles on polyelectrolyte
      superstructure forming an electroluminescent "necklace-of-beads".
AB  - We report a nonmicellar method to synthesize monodisperse semiconducting
      nanoparticles templated on polymer chains dissolved in solution at high yield.
      The monodispersity is achieved due to the beaded necklace morphology of the
      polyelectrolyte chains in solution where the beads are nanometer-scale nodules in
      the polymer chain. The resultant structure is a nanoparticles studded necklace
      where the particles are imbedded in the beads. Multiple cycles of synthesis on
      the polymer template yield nanoparticles of identical size, resulting in a
      nanocomposite with high particle fraction. The resultant nanocomposite has beaded
      fibrilar morphology with imbedded nanoparticles and can be solution-casted to
      make electroluminescent thin film device.

PMID- 17014095
TI  - Polymer surface reorientation after protein adsorption.
AB  - Surface side-chain orientation changes of two polymers have been observed upon
      protein adsorption using sum frequency generation vibrational spectroscopy. Side
      chain-deuterated poly(ethyl methacrylate) and poly(n-butyl methacrylate) were
      contacted with five protein solutions: albumin, fibrinogen, ubiquitin, cytochrome
      c, and lysozyme. The CD(3)/CD(2) symmetric stretch ratios of the surface polymer
      side chains in contact with these different media were compared to each other and
      to that of the polymer contacting air or phosphate buffered saline. The
      adsorption of different proteins to the surfaces resulted in polymer side-chain
      orientations slightly different from each other, with orientations between the
      air and buffer cases.

PMID- 17014096
TI  - Synthesis of silica-gold nanocomposites and their porous nanoparticles by an in
      situ approach.
AB  - We demonstrate the one-step synthesis of a silica-gold nanocomposite by
      simultaneous hydrolysis and reduction of gold chloride. The aminophenyl group was
      used as a reducing agent, and the trimethoxy silane group acts a precursor for
      the formation of silica. The porous gold nanoparticles were formed by etching out
      the silica-gold nanocomposite by hydrofluoric acid. The electron diffraction of
      porous gold nanoparticles showed that the particle are polycrystalline with FCC
      structure. The silica-gold nanocomposite exhibited nonlinear current-voltage
      behavior, and the porous gold nanoparticles displayed linear current-voltage
      behavior.

PMID- 17014097
TI  - Selective assembly and alignment of actin filaments with desired polarity on
      solid substrates.
AB  - We report a new strategy to selectively assemble and align filamentous actin (F
      actin) onto desired locations on a solid substrate with a specific structural
      polarity. In this strategy, biotinylated gelsolin caps the structural minus end
      of F-actin so that the F-actin binds onto a streptavidin pattern with a specific
      structural polarity. We also demonstrate that an electric field can be utilized
      to align bound F-actin along a desired direction. This can be one of the major
      technical breakthroughs toward the assembly of nanomechanical systems based on
      myosin biomotors.

PMID- 17014098
TI  - Toward the innovative synthesis of columnar CeO2 nanostructures.
AB  - We report on the preparation of supported columnar CeO(2) nanostructures by a
      simple catalyst-free chemical vapor deposition process at temperatures as low as
      623 K. A suitable choice of experimental parameters enables us to control the
      structural and morphological features of the resulting ceria nanosystems.

PMID- 17014099
TI  - Tunable instability mechanisms of polymer thin films by molecular self-assembly.
AB  - Incorporation of a block copolymer into a thin polymer film is observed to alter
      both the rate and mechanism by which the film dewets from an immiscible polymer
      substrate. Films with little or no copolymer dewet by classical nucleation and
      growth of circular holes, and the dewetting rate decreases with increasing
      copolymer concentration. Increasing the copolymer content at constant film
      thickness generates copolymer micelles that adsorb/aggregate along the
      polymer/polymer interface and promote nonclassical dewetting fluctuations similar
      in appearance to spinodal dewetting. At higher copolymer concentrations,
      dewetting proceeds after a lengthy induction period by the nucleation and growth
      of flower-shaped holes suggestive of film pinning or viscous fingering. Atomic
      force microscopy of the polymer/polymer interface after removal of the top film
      by selective dissolution reveals substantial structural development due to
      copolymer self-assembly.

PMID- 17014100
TI  - Positional isomers of linear sodium dodecyl benzene sulfonate: solubility, self
      assembly, and air/water interfacial activity.
AB  - Commercial linear alkyl benzene sulfonates (ABS) are a very important class of
      anionic surfactants that are employed in a wide variety of applications,
      especially those involving wetting and detergency. Linear ABS surfactants
      generally consist of a complex mixture of different chain lengths and positional
      isomers. This diversity and level of complexity makes it difficult to develop
      fundamental structure-property correlations for the commercial surfactants. In
      this work, six monodisperse headgroup positional isomers of sodium para-dodecyl
      benzene sulfonate (Na-x-DBS, x = 1-6) have been studied. The influence of
      headgroup position and added electrolyte (NaCl) on the solubility and self
      assembly (micellar and vesicular aggregation and lyotropic liquid crystalline
      phase behavior) in the temperature range from 10 to 90 degrees C have been
      investigated. Additionally, the air-aqueous solution interfacial adsorption at 25
      (no added NaCl) and 50 degrees C (from 0 to 1.0 M added NaCl) has been examined.
      The observed physicochemical behavior is interpreted in terms of local molecular
      packing constraints, and in the case of the lyotropic liquid crystalline behavior
      global aggregate packing constraints as well.

PMID- 17014101
TI  - Study of tetrabutylammonium perfluorooctanoate aqueous solutions with two cloud
      points by dielectric relaxation spectroscopy.
AB  - Dielectric relaxation spectra of tetrabutylammonium perfluorooctanoate (TBPFO),
      an anionic fluorocarbon surfactant with two cloud points in aqueous solution,
      were investigated in the frequency range from 40 Hz to 110 MHz. Striking
      dielectric relaxations were observed when both the temperature-dependent and
      concentration-dependent phase transitions in TBPFO aqueous solution occurred. The
      changes in dielectric relaxation and the distribution of dielectric parameters
      were consistent with the phase boundaries of the phase diagram. In the first
      homogeneous phase region, two relaxations of rodlike micelles appeared at about
      100 kHz and 5 MHz, which originated from the diffusion of the free counterions in
      the directions of the long axis and the short axis of rodlike micelles,
      respectively. With increasing temperature, two relaxations gradually turned to
      one as a result of the formation of connected or entanglement points between the
      wormlike micelles. The lengths of the long half-axis and the short half-axis of
      the rodlike micelles, as well as the average distance of the connected or
      entanglement points of the wormlike micelles, were evaluated by the obtained
      relaxation times.

PMID- 17014102
TI  - Interactions between gemini surfactants, 12-s-12, and beta-cyclodextrin as
      investigated by NMR diffusometry and electric conductometry.
AB  - The interaction between beta-cyclodextrin (CD) and gemini surfactant of the type
      alkyl-alpha,omega-bis(dodecyldimethylammonium bromide) with different spacer
      lengths of 2, 8, and 10 carbons has been investigated by means of electric
      conductivity (EC) and proton self-diffusion NMR at 298 K. The formation of a 2:1
      (CD:gemini) complex in a two-step mechanism is observed with the first
      association constant (K(11)) higher than the second one (K(21)), but both
      relatively small in comparison with single C(12)-tailed surfactant. The value of
      the association constants increased with spacer length both for the first and
      second associated CD, which indicates that the available space on the gemini
      molecule is important. The magnitudes of the association constant both for the
      first and second complexation are discussed. The first association constant is
      small (when compared with the homologous single-chain surfactant) due to
      hydrophobic interaction between the hydrocarbon tails within the gemini molecule,
      while the second association constant shows no cooperativity and its magnitude is
      discussed in terms of steric constrains.

PMID- 17014103
TI  - Peptides on GaAs surfaces: comparison between features generated by microcontact
      printing and dip-pen nanolithography.
AB  - Atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and
      Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS) were
      employed to understand the size, composition, and conformation of lithographic
      patterns composed of peptide molecules. GaAs surfaces were patterned by
      microcontact printing (microCP) and dip-pen nanolithography (DPN) using a peptide
      sequence composed of 15 amino acids. The detailed surface evaluation showed that
      the patterns have similar chemical compositions but differ in the bonding among
      the molecules anchored on the GaAs substrate. Both types of patterns were
      crystalline-like in nature. The features created by DPN exhibited interchain
      hydrogen bonding, while the ones generated by microCP displayed non-hydrogen
      bonding. The differences in the lithographic structures can be utilized in future
      biorecognition experiments that take advantage of the electronic properties of
      the GaAs substrate and the tunable behavior of the covalently anchored
      biomolecules on the surface.

PMID- 17014104
TI  - Surfactant design for the 1,1,1,2-tetrafluoroethane-water interface: ab initio
      calculations and in situ high-pressure tensiometry.
AB  - In situ high-pressure tensiometry and ab initio calculations were used to
      rationally design surfactants for the 1,1,1,2-tetrafluoroethane-water (HFA134a|W)
      interface. Nonbonded pair interaction (binding) energies (E(b)) of the complexes
      between HFA134a and candidate surfactant tails were used to quantify the HFA
      philicity of selected moieties. The interaction between HFA134a and an ether
      based tail was shown to be predominantly electrostatic in nature and much more
      favorable than that between HFA134a and a methyl-based fragment. The interfacial
      activity of (i) amphiphiles typically found in FDA-approved pressurized metered
      dose inhaler (pMDI) formulations, (ii) a series of nonionic surfactants with
      methylene-based tails, and (iii) a series of nonionic surfactants with ether
      based tails was investigated at the HFA134a|W interface using in situ
      tensiometry. This is the first time that the tension of the surfactant-modified
      HFA134a|W interface has been reported in the literature. The ether-based
      surfactants were shown to be very interfacially active, with tension decreasing
      by as much as 27 mN.m(-)(1). However, the methyl-based surfactants, including
      those from FDA-approved formulations, did not exhibit high activity at the
      HFA134a|W interface. These results are in direct agreement with the E(b)
      calculations. Significant differences in interfacial activity are noted for
      surfactants at the 2H,3H-perfluoropentane (HPFP)|water and HFA134a|W interfaces.
      Care should be taken, therefore, when results from the mimicking solvent (HPFP)
      are extrapolated to HFA134a-based systems. The results shown here are of
      relevance in the selection of surfactants capable of forming and stabilizing
      reverse aqueous aggregates in HFA-based pMDIs, which are promising formulations
      for the systemic delivery of biomolecules to and through the lungs.

PMID- 17014105
TI  - Electrochemical and spectroscopic characterization of organic compound uptake in
      silica core-shell nanocapsules.
AB  - Oil-filled silica nanocapsules consisting of a hydrophobic liquid core and a
      silicate shell have been shown to efficiently extract hydrophobic compounds from
      aqueous media. With a view toward quantifying the selectivity of these systems, a
      series of electrochemical and spectroscopic measurements was performed. Uptake
      and kinetics experiments were carried out through electrochemical measurements by
      using solutions of lipophilic electroactive molecules of different sizes and with
      different affinities for silica. Other solutions with fluorescent probes were
      used for spectrophotometry measurements. In this work we report the environment
      where the lipophilic compounds studied end up after absorption and the kinetics
      of their uptake by the oil-filled silica nanocapsules with different shell
      thicknesses.

PMID- 17014106
TI  - Induced phase separation in low-ionic-strength cellulose nanocrystal suspensions
      containing high-molecular-weight blue dextrans.
AB  - Spontaneous entropic phase separation phenomena occur in a wide range of systems
      containing highly anisotropic colloidal particles. Among these are aqueous
      suspensions of negatively charged cellulose I nanocrystals produced by sulfuric
      acid hydrolysis of native cellulose, which phase separate into isotropic and
      chiral nematic liquid-crystalline phases. Phase separation of an isotropic phase
      from a completely ordered nanocrystal suspension may be induced by the addition
      of salts or nonadsorbing macromolecules. In previous work (Edgar, C. D.; Gray, D.
      G. Macromolecules 2002, 35, 7400-7406), an isotropic phase was found to form over
      a period of several days when blue dextran (a sulfonated triazine dye, Cibacron
      blue 3G-A, covalently attached to high-molecular-weight dextran chains) was added
      to initially ordered suspensions. Here we report work showing that the observed
      phase separation was associated with the charged dye molecules attached to the
      dextran. The Cibacron blue 3G-A dye attached to blue dextran was found to induce
      greater phase separation than free (unbound) dye; at increasing ionic strength,
      depletion attractions due to the blue dextran increasingly contribute to the
      phase separation.

PMID- 17014107
TI  - Nanoparticle-containing structures as a substrate for surface-enhanced Raman
      scattering.
AB  - Metallic nanostructures were prepared through the alternate immersion of
      derivatized glass slides in solutions of gold nanoparticles (NPs) and a
      propanedithiol linker molecule. Nanostructures consisting of 1-17 depositions of
      gold NPs were synthesized, and these substrates were characterized using UV-vis
      spectroscopy and atomic force microscopy. Subsequently, the surface-enhanced
      Raman scattering (SERS) of oxazine 720 was obtained at two excitation wavelengths
      (632 and 785 nm) from all substrates. Maximum SERS enhancement was observed for 9
      and 13 NP depositions for 632 and 785 nm excitations, respectively. The
      difference in the number of NP depositions required for maximum enhancement is
      attributed to different wavelengths which can excite distinct aggregate
      structures within the metallic substrate. Therefore, these NP-containing
      structures can be "tuned" to yield maximum SERS enhancement for the excitation
      source being used by varying the number of NP depositions.

PMID- 17014108
TI  - Theory of surface micelles of semifluorinated alkanes.
AB  - Surface structures of semifluorinated alkanes F(CF(2))(n)(CH(2))(m)H (referred to
      as FnHm) spread on the air/water interface are investigated theoretically. The
      study is focused on the disklike surface micelles that were recently identified
      by AFM and scattering techniques at sufficiently high surface concentrations. We
      show that (1) the micelles emerge as a result of liquid/liquid (rather than
      liquid/gas) phase separation in the Langmuir layer; (2) the micelles are islands
      of the higher-density phase with roughly vertical orientation of FnHm molecules
      (F-parts extend toward air, H-parts toward water) and the matrix is the lower
      density-phase where the FnHm diblocks are nearly parallel to the water surface;
      (3) the micelles and the hexagonal structure they form are stabilized by the
      electrostatic interactions which are mainly due to the vertical dipole moments of
      the CF(2)- CH(2) bonds in the vertical phase; and (4) the electrostatic repulsive
      interactions can serve to suppress the micelle size polydispersity.

PMID- 17014109
TI  - Ion pairs of crystal violet in sodium bis(2-ethylhexyl)sulfosuccinate reverse
      micelles.
AB  - The interfacial localization and the ion pair formation of the positively charged
      dye crystal violet (CV) in sodium bis(2-ethylhexyl)sulfosuccinate reverse
      micelles (AOT RMs) were studied by several structural and spectroscopic
      techniques and by quantum chemical calculations. The size and shape of the AOT
      RMs in the presence of CV were investigated by small-angle X-ray scattering,
      showing that CV does not significantly change the RM structure. CV localization
      as a function of the water to surfactant molar ratio (w(0)) was characterized by
      H(1) and (13)C NMR, indicating the close proximity of CV to the sulfosuccinate
      group of AOT at small and large w(0) values. These results were confirmed by
      calculation of magnetic shielding constants using the gauge-independent atomic
      orbital method with the HF/6-31G(d) basis set. Two different types of ion pairs
      between AOT and CV, i.e., contact ion pair (CIPs) and solvent-separated ion pair
      (SSIPs), were characterized by UV-vis spectroscopy and quantum chemical
      calculations using the semiempirical ZINDO-CI method. In nonpolar isotropic
      solvents CIPs are formed with an association constant (K(ASSOC)) of 2 x 10(4)
      mol(-1) L in isooctane and 750 mol(-1) L in chloroform. In AOT RMs at low w(0),
      CV-AOT CIPs are also formed. By increasing w(0), there is a sharp decrease in the
      CIP association free energy, and SSIPs are formed. (CV(+))(H(2)O)(AOT(-)) SSIPs
      are stable in the AOT RM up to the largest w(0) tested (w(0) = 33).

PMID- 17014110
TI  - Incorporation of nonionic emulsifiers inside particles in emulsion
      polymerization: mechanism and methods of suppression.
AB  - Emulsion polymerizations of styrene were carried out using two kinds of
      polyoxyethylene lauryl ether nonionic emulsifiers having different hydrophilic
      lipophilic balances (HLB): Emulgen 109P (HLB 13.6); and Emulgen 150 (HLB 18.3).
      In both cases, incorporation of emulsifier inside polystyrene (PS) particles was
      clearly observed, as previously reported for the emulsion polymerization of
      styrene and methacrylic acid using polyoxyethylene nonyl phenyl ether (Emulgen
      911, HLB 13.7) nonionic emulsifier. The generality of the incorporation
      phenomenon of nonionic emulsifier inside polymer particles in emulsion
      polymerization was clarified. In the case of Emulgen 109P, which is more
      hydrophobic than Emulgen 150, about 30% of the total amount was incorporated
      inside the PS particles, higher than for Emulgen 150 (15%). The difference seemed
      to be ascribed to the difference in the affinities between the nonionic
      emulsifiers and styrene, which cause the incorporation of emulsifier. On the
      basis of this idea, suppression of the incorporation was achieved by decreasing
      the polymerization temperature and the monomer-feed rate. This strongly supports
      the proposed incorporation mechanism.

PMID- 17014111
TI  - Effect of counterions on the activity of lipase in cationic water-in-oil
      microemulsions.
AB  - This paper delineates how the different counterions affect the physicochemical
      properties of the aqueous aggregates and thereby the lipase activities at the
      interface of cationic water-in-oil microemulsions. To this end, we have
      synthesized a series of cetyltrimethylammonium-based surfactants, 1-14, having
      aliphatic, aliphatic with aromatic substitution at the alpha position, and
      aromatic carboxylate anion as the counterion. The physicochemical
      characterizations of these aqueous aggregates were done by conductometric,
      tensiometric, fluorometric techniques to determine counterion binding (beta),
      critical micelle concentration (cmc), and micropolarity at the microenvironment.
      It has been found that the activity of lipase mainly increases with
      hydrophobicity (which is directly proportional to the counterion binding (beta)
      of the surfactant) of the counterion and reaches a maximum when the beta value is
      around 0.5. Increase in hydrophobicity as well as beta leads to the attachment of
      more counterions at interface resulting in enhancement of interfacial area.
      Consequently, the enzyme may attain flexible secondary conformation at the
      augmented surface area and also allow larger population of substrates and enzyme
      molecules at the interface leading to the enhancement in lipase activity. After
      an optimum value of beta, further increase probably produces a steric crowding at
      the interface, hindering the smooth occupancy of enzyme and the substrate in this
      region leading to decrease of enzyme activity, while molecular surface area of
      the counterion did not show any virtual influence on the lipase activity. Thus,
      the variation in the counterion structure and hydrophobicity plays a crucial role
      in modulating the lipase activity.

PMID- 17014112
TI  - Headgroup hydration and mobility of DOTAP/DOPC bilayers: a fluorescence solvent
      relaxation study.
AB  - The biophysical properties of liposome surfaces are critical for interactions
      between lipid aggregates and macromolecules. Liposomes formed from cationic
      lipids, commonly used to deliver genes into cells in vitro and in vivo, are an
      example of such a system. We apply the fluorescence solvent relaxation technique
      to study the structure and dynamics of fully hydrated liquid crystalline lipid
      bilayers composed of mixtures of cationic dioleoyltrimethylammoniumpropane
      (DOTAP) and neutral dioleoylphosphatidylcholine (DOPC). Using three different
      naphthalene derivatives as fluorescent dyes (Patman, Laurdan and Prodan) allowed
      different parts of the headgroup region to be probed. Wavelength-dependent
      parallax quenching measurements resulted in the precise determination of Laurdan
      and Patman locations within the DOPC bilayer. Acrylamide quenching experiments
      were used to examine DOTAP-induced dye relocalization. The nonmonotonic
      dependence of dipolar relaxation kinetics (occurring exclusively on the
      nanosecond time scale) on DOTAP content in the membrane was found to exhibit a
      maximum mean solvent relaxation time at 30 mol % of DOTAP. Up to 30 mol %,
      addition of DOTAP does not influence the amount of bound water at the level of
      the sn(1) carbonyls, but leads to an increased packing of phospholipid
      headgroups. Above this concentration, elevated lipid bilayer water penetration
      was observed.

PMID- 17014113
TI  - Evolution of gel structure during thermal processing of Na-geopolymer gels.
AB  - The present work examines how the gel structure and phase composition of Na
      geopolymers derived from metakaolin with varied Si/Al ratio evolve with exposure
      to temperatures up to 1000 degrees C. Gels were thermally treated and
      characterized using quantitative XRD, DTA, and FTIR to elucidate the changes in
      gel structure, phase composition, and porosity at each stage of heating. It is
      found that the phase stability, defined by the amount and onset temperature of
      crystallization, is improved at higher Si/Al ratios. Two different mechanisms of
      densification have been isolated by FTIR, related to viscous flow and collapse of
      the highly distributed pore network in the gel. Gels with low Si/Al ratio only
      experience viscous flow that correlates with low thermal shrinkage. Gels at a
      higher Si/Al ratio, which have a homogeneous microstructure composed of a highly
      distributed porosity, undergo both densification processes corresponding to a
      large extent of thermal shrinkage during densification. This work elucidates the
      intimate relationship between gel microstructure, chemistry, and thermal
      evolution of Na-geopolymer gels.

PMID- 17014114
TI  - Interaction of hydrogen with unsupported and supported nickel.
AB  - The adsorption of molecular hydrogen on Ni powder and on Ni/Al(2)O(3) and
      Ni/SiO(2) catalysts was studied by the temperature-programmed desorption (TPD)
      method. The examinations were performed in the flow system, starting the TP
      measurements at low temperatures of 100 or 78 K, which resulted in the formation
      of complete characteristics of the interaction of hydrogen with nickel.
      Generally, three forms of chemisorbed hydrogen were distinguished: alpha,
      adsorbed on Ni surface, beta, adsorbed in the "second layer", and gamma, located
      in the subsurface region of nickel. The comparison of the results of this work
      with those obtained in vacuum systems for various Ni surfaces has led to the
      conclusion that the same form of hydrogen desorbs from nickel above 200 K in
      vacuum systems but above 300 K in flow systems. The examinations performed for
      Ni/Al(2)O(3) and Ni/SiO(2) samples show that alumina suppresses but silica
      enhances the formation of the beta-form of hydrogen.

PMID- 17014115
TI  - Wetting behavior of porous silicon surfaces functionalized with a
      fulleropyrrolidine.
AB  - We report the immobilization of a fulleropyrrolidine, bearing a dec-9-ynyl
      functionality, on silicon surfaces through a thermal hydrosilylation protocol.
      Contact angle measurements on porous silicon (PS) surfaces reveal an unusual
      dependence of the angle with the PS roughness that apparently contradicts
      Wenzel's formula. This result has been explained by an extension of Wenzel's
      model in which the critical angle, which discriminates between the
      hydrophilic/hydrophobic character of a solid material, is substantially reduced
      below 90 degrees by surface roughness.

PMID- 17014116
TI  - Adsorption of hydrophobically modified starch at oil/water interfaces during
      emulsification.
AB  - The adsorption of starch that had been hydrophobically modified with octenyl
      succinate anhydride (OSA) at the oil/water interface during emulsification was
      studied. The starch samples were of waxy barley origin and were varied in molar
      mass and degree of substitution (DS). The particle size of the emulsions was
      measured and the adsorbed amount of starch was determined through serum
      depletion. The results show that adsorption is governed by the relationship
      between interfacial area and OSA-starch concentration. The surface load of OSA
      starch can in some cases become very high, reaching 16 mg/m(2). The
      emulsification occurs under nonequilibrium and turbulent flow conditions. Under
      these conditions kinetic factors are likely to play an important role in the
      adsorption process. Turbulent flow favors transport to the interface of larger
      molecules over small ones, which could lead to higher surface loads by causing
      jamming at the interface. A model that treats the adsorption as a collision
      between particles in turbulent flow has been used, and it shows that the
      adsorption time of a polymer decreases with increasing polymer radius. It also
      shows that the time scale of adsorption is shorter than the time scales for
      configurational changes of macromolecules at interfaces and that emulsion droplet
      droplet collisions are of similar time scales as adsorption, which gives further
      indications that kinetic factors are important during adsorption. The simulation
      results give a reasonable explanation to why large molecules such as OSA-starch
      can be efficient as emulsifiers.

PMID- 17014117
TI  - Ferrocenyl-functionalized silica nanoparticles: preparation, characterization,
      and molecular recognition at interfaces.
AB  - Ferrocenyl-functionalized silica nanoparticles (Fc-SiO(2), 6a-6c) of about 60 nm
      with supramolecular "guest" properties were prepared. Nanoparticles 6a-6c
      differed by the addition of different molar ratios of starting compounds during
      the functionalization step, i.e., 1:0, 1:10, and 1:90 of 2-ferrocenyl
      amidoethoxyethanol and diethylene glycol for 6a,6b, and 6c, respectively. X-ray
      photoelectron spectroscopy (XPS) proved the presence of ferrocenyl groups on the
      surfaces of 6a-6c, whereas the elemental analysis revealed an iron content of
      particles 6a-6c of 0.10-0.16%. Dynamic light scattering (DLS) results showed
      that, compared with 6a, 6b dispersed well in aqueous media, possibly due to the
      presence of diethylene glycol at the surfaces of 6b that significantly increases
      its overall hydrophilicity. Cyclic voltammetry of 6b indicated a totally
      irreversible system and a "mixed" diffusion-adsorption behavior, which is
      attributed to sluggish electron transfer. The shifted |I(p,C)/I(p,A*)| ratio
      showed that the ferrocenyl groups are robustly attached to the nanoparticle
      surface within the experimental potential range. The supramolecular recognition
      of Fc-SiO(2) nanoparticles at interfaces was verified by their adsorption on beta
      cyclodextrin (beta-CD) self-assembled monolayers, as monitored by surface plasmon
      resonance (SPR) spectroscopy. The ability of the Fc-SiO(2) nanoparticles to form
      host-guest interactions was also demonstrated by the attachment of beta-CD
      functionalized Au nanoparticles (2.8 nm) on the Fc-SiO(2) surfaces, when mixed in
      solution.

PMID- 17014118
TI  - Hydrogen adsorption measurements and modeling on metal-organic frameworks and
      single-walled carbon nanotubes.
AB  - Hydrogen adsorption measurements on Al-, Cr-, and Zn-based metal-organic
      frameworks (MOFs) and single-walled carbon nanotubes (SWNTs) are presented. The
      measurements were performed at temperatures ranging from 77 to 300 K and
      pressures up to 50 atm using a volumetric approach. The maximum excess adsorption
      at 77 K ranges from 2.3 to 3.9 wt % for the MOFs and from 1.5 to 2.5 wt % for the
      SWNTs. These values are reached at pressures below 40 atm. At room temperature
      and 40 atm, modest amounts of hydrogen are adsorbed (<0.4 wt %). A Dubinin
      Astakhov (DA) approach is used to investigate the measured adsorption isotherms
      and to retrieve energetic and structural parameters. The adsorption enthalpy
      averaged over filling is about 2.9 kJ/mol for the MOF-5 and about 3.6-4.2 kJ/mol
      for SWNTs.

PMID- 17014119
TI  - Water behavior revisited at the air/ionic solution and silica/ionic solution
      interfaces. Extension to coadsorption of ions and organic molecules.
AB  - This paper reports on investigations about the adsorption at the air-water
      surface, and for the sake of comparison at the silica-solution interface, of two
      1-2 electrolytes, Pb(NO(3))(2) and PbCl(2), at first alone and then from a
      mixture with carbofuran or with benzene; all of them were at concentrations below
      10(-2) M. The limited domain, where the Debye and Huckel formalism for solutions
      and the Wagner-Onsager-Samaras (WOS) model for surfaces are correct, is then
      respected. This study was aimed at trying to identify the part played in the
      surface by the different particles of the system components and in particular the
      role of water. When aqueous solutions of nonorganic salts are dilute enough,
      their surface tensions are known to be salt concentration-independent; however,
      the zero value of the resulting relative adsorption has never been the subject of
      analysis about water behavior. By combining experimental relative adsorptions and
      Gibbs excesses calculated from the WOS theory, we will show that, in well-known
      solutions such as KCl ones, where the negative excess in salt can be very
      precisely modeled by the WOS theory, the resulting water excess Gamma(W) is
      negative. The same result can be obtained by taking into account the Ray-Jones
      effect. This observation drove us to wonder about the results of a similar
      analysis done on solutions of unsymmetrical electrolytes and on mixtures of salt
      and organic molecules. Experiments showed that, for all of the systems, Gamma(W)
      was negative. For a given salt, Gamma(W) was more negative in the presence of
      organic molecules, and carbofuran was a more efficient water repellent than
      benzene; water repulsion was greater with nitrates than with chlorides. From
      these data, it seems that water was repelled toward the solution bulk, whereas
      ions probably took place between the bulk and a layer of organic molecules. These
      observations called for a more detailed modeling.

PMID- 17014120
TI  - Molecular level structures of poly(n-alkyl methacrylate)s with different side
      chain lengths at the polymer/air and polymer/water interfaces.
AB  - Sum frequency generation (SFG) vibrational spectroscopy has been successfully
      applied to study molecular structures of several poly(n-alkyl methacrylate)s
      (PAMAs) with different side chain lengths at the PAMA/air and PAMA/water
      interfaces. We have observed that the ester side chains from all PAMAs always
      dominate the interface, but the orientation information of the methyl end group
      on the side chains varies, depending on the length of the side chain. The
      contributions from methylene groups on the side chains have been evaluated, and
      the surface structures have been related to the surface tension of these
      polymers. Different water restructuring behaviors have been observed for
      different PAMAs. This phenomenon and its reversibility are strongly dependent on
      the glass transition temperature of each polymer, which is influenced by the side
      chain length. Detailed data fitting and analysis has been discussed.

PMID- 17014121
TI  - Heterogeneous electron transfer processes in self-assembled monolayers of amine
      terminated conjugated molecular wires.
AB  - A versatile synthesis of triarylamine and phenothiazine end-capped
      oligo(phenyleneacetylene) molecular wires which are terminated by thiol functions
      is described. The repetitive synthesis allows the preparation of molecular wires
      with different chain length and different substituents attached to the wire
      backbone. These molecular wires were used to form dense self-assembled monolayers
      (SAM) on gold substrates as proved by cyclic voltammetry and quartz crystal
      microbalance measurements. The heterogeneous electron transfer rate constant of
      these SAMs was measured by impedance spectroscopy between 1 MHz and 0.1 Hz. The
      rate constants are somewhat larger for the triarylamine terminated systems than
      for the phenothiazine compound, due to the higher reorganization energy in the
      latter. While the molecular wires with electron withdrawing substituents display
      an electron transfer which is slow enough to be measurable with our impedance
      setup, we were unable to determine the rate of molecular wires with electron
      donating substituents.

PMID- 17014122
TI  - Synthesis and characterization of amphiphilic phenylene ethynylene oligomers and
      their Langmuir-Blodgett films.
AB  - We report the synthesis of a series of amphiphilic molecular building blocks that
      can be self-assembled at the air-water interface to form two- and three
      dimensional nanostructures with tunable optoelectronic properties. Compression of
      these molecular building blocks using the Langmuir-Blodgett method gives rise to
      monolayer and multilayer thin films with different packing densities and
      electronic properties that are tunable due to varying pi-pi (hydrophobic)
      interactions. Depending on the noncovalent interaction between chromophores, we
      observe a transition toward denser packing with increasing number of phenylene
      ethynylene repeat units. Additionally, we use quantum-chemical simulations to
      help determine the excited-state electronic structure, intermolecular
      interactions, and packing trends. Our results demonstrate that the interplay
      between dipole-dipole and pi-pi interactions dominates the formation of thin
      films with various packing densities and determines the associated optical
      properties.

PMID- 17014123
TI  - Structural analysis of PEO-PBO copolymer monolayers at the air-water interface.
AB  - X-ray reflectivity (XR) and grazing incidence X-ray diffraction (GIXD) have been
      used to examine an oxyethylene-b-oxybutylene (E(23)B(8)) copolymer film at the
      air-water interface. The XR data were fitted using both a one- and a two-layer
      model that outputted the film thickness, roughness, and electron density. The
      best fit to the experimental data was obtained using a two-layer model
      (representing the oxyethylene and oxybutylene blocks, respectively), which showed
      a rapid thickening of the copolymer film at pressures above 7 mN/m. The large
      roughness values found indicate a significant degree of intermixing between the
      blocks and back up the GIXD data, which showed no long range lateral ordering
      within the layer. It was found from the electron density model results that there
      is a large film densification at 7 mN/m, possibly suggesting conformational
      changes within the film, even though no such change occurs on the pressure-area
      isotherm at the same surface pressure.

PMID- 17014124
TI  - Microscopic and thermodynamic properties of the HFA134a-water interface:
      atomistic computer simulations and tensiometry under pressure.
AB  - A combined computational and experimental approach is used to determine the
      interfacial thermodynamic and structural properties of the liquid 1,1,1,2
      tetrafluoroethane (HFA134a)-vapor and liquid HFA134a-water (HFA134a|W) interfaces
      at 298 K and saturation pressure. Molecular dynamics (MD) computer simulations
      reveal a stable interface between HFA134a and water. The "10-90" interfacial
      thickness is comparable with those typically reported for organic-water systems.
      The interfacial tension of the HFA134a|W interface obtained from the pressure
      tensor analysis of the MD trajectory is in good agreement with the experimental
      value determined using in situ high-pressure tensiometry. These results indicate
      that the potential models utilized are capable of describing the intermolecular
      interactions between these two fluids. The tension of the HFA134a|W interface is
      significantly lower than those typically observed for conventional oil-water
      interfaces and similar to that of the compressed CO(2)-water interface, observed
      at moderate CO(2) pressures. The MD and tensiometric results are also compared
      and contrasted with the HFA134a|W and chlorofluorocarbon-water tension values
      estimated from a parametric relationship. This represents the first report of the
      interfacial and microscopic properties of the (propellant) hydrofluoroalkanes
      (HFA)|W interface. The results presented here are of relevance in the design of
      surfactants capable of forming and stabilizing water-in-HFA microemulsions.
      Reverse aqueous microemulsions in HFA-based pressurized metered-dose inhalers are
      candidate formulations for the systemic delivery of biomolecules to and through
      the lungs.

PMID- 17014125
TI  - Colloidal interactions between Langmuir-Blodgett bitumen films and fine solid
      particles.
AB  - In oil sand processing, accumulation of surface-active compounds at various
      interfaces imposes a significant impact on bitumen recovery and bitumen froth
      cleaning (i.e., froth treatment) by altering the interfacial properties and
      colloidal interactions among various oil sand components. In the present study,
      bitumen films were prepared at toluene/water interfaces using a Langmuir-Blodgett
      (LB) upstroke deposition technique. The surface of the prepared LB bitumen films
      was found to be hydrophobic, comprised of wormlike aggregates containing a
      relatively high content of oxygen, sulfur, and nitrogen, indicating an
      accumulation of surface-active compounds in the films. Using an atomic force
      microscope, colloidal interactions between the LB bitumen films and fine solids
      (model silica particles and clay particles chosen directly from an oil sand
      tailing stream) were measured in industrial plant process water and compared with
      those measured in simple electrolyte solutions of controlled pH and divalent
      cation concentrations. The results show a stronger long-range repulsive force and
      weaker adhesion force in solutions of higher pH and lower divalent cation
      concentration. In plant process water, a moderate long-range repulsive force and
      weak adhesion were measured despite its high electrolyte content. These findings
      provide more insight into the mechanisms of bitumen extraction and froth
      treatment.

PMID- 17014126
TI  - Influence of the polyelectrolyte poly(ethyleneimine) on the adsorption of
      surfactant mixtures of sodium dodecyl sulfate and monododecyl hexaethylene glycol
      at the air-solution interface.
AB  - The polyelectrolyte poly(ethylenenimine), PEI, is shown to strongly influence the
      adsorption of the anionic-nonionic surfactant mixture of sodium dodecyl sulfate,
      SDS, and monododecyl hexaethylene glycol, C(12)E(6), at the air-solution
      interface. In the presence of PEI, the partitioning of the mixed surfactants to
      the interface is highly pH-dependent. The adsorption is more strongly biased to
      the SDS as the pH increases, as the PEI becomes a weaker polyelectrolyte. At
      surfactant concentrations >10(-4) M, the strong interaction and adsorption result
      in multilayer formation at the interface, and this covers a more extensive range
      of surfactant concentrations at higher pH values. The results are consistent with
      a strong interaction between SDS and PEI at the surface that is not predominantly
      electrostatic in origin. It provides an attractive route to selectively
      manipulate the adsorption and composition of surfactant mixtures at interfaces.

PMID- 17014127
TI  - Structural effects recorded for AFM tips interacting with individual
      nanoparticles and their clusters deposited on substrates.
AB  - Mica and alumina were coated with nanoparticles using aqueous suspensions while
      managing attractive substrate-particle electrostatic forces. Using nanoparticle
      coated substrates, structural forces were measured for 10 nm silica particles
      deposited on the alumina substrate and 5-80 nm alumina particles on mica using an
      atomic force microscopy technique. For nanoparticles forming clusters,
      oscillation of structural forces was recorded with a periodicity that is close to
      the size of nanoparticles used. Positioning the AFM tip over the single particles
      allowed, on the other hand, the study of probe-nanoparticle colloidal forces.

PMID- 17014128
TI  - Discontinuous liquid rise in capillaries with varying cross-sections.
AB  - We consider theoretically liquid rise against gravity in capillaries with height
      dependent cross-sections. For a conical capillary made from a hydrophobic surface
      and dipped in a liquid reservoir, the equilibrium liquid height depends on the
      cone-opening angle alpha, the Young-Dupre contact angle theta, the cone radius at
      the reservoir's level R(0), and the capillary length kappa(-)(1). As alpha is
      increased from zero, the meniscus' position changes continuously until, when
      alpha attains a critical value, the meniscus jumps to the bottom of the
      capillary. For hydrophilic surfaces the meniscus jumps to the top. The same
      liquid height discontinuity can be achieved with electrowetting with no
      mechanical motion. Essentially the same behavior is found for two tilted
      surfaces. We further consider capillaries with periodic radius modulations and
      find that there are few competing minima for the meniscus location. A transition
      from one to another can be performed by the use of electrowetting. Finite
      pressure difference between the two sides of the liquids can be incorporated as
      well, resulting in complicated phase-diagrams in the alpha-theta plane. The
      phenomenon discussed here may find uses in microfluidic applications requiring
      the transport small amounts of water "quanta" (volume < 1 nL) in a regular
      fashion.

PMID- 17014129
TI  - Dropwise condensation: experiments and simulations of nucleation and growth of
      water drops in a cooling system.
AB  - Dropwise condensation of water vapor from a naturally cooling, hot water
      reservoir onto a hydrophobic polymer film and a silanized glass slide was studied
      by direct observation and simulations. The observed drop growth kinetics suggests
      that smallest drops grow principally by the diffusion of water adsorbed on the
      substrate to the drop perimeter, while drops larger than about 50 microm in
      diameter grow principally by direct deposition from the vapor onto the drop
      surface. Drop coalescence plays a critical role in determining the drop-size
      distribution and stimulates the nucleation of new, small drops on the substrates.
      Simulations of drop growth incorporating these growth mechanisms provide a good
      description of the observed drop-size distribution. Because of the large role
      played by coalescence, details of individual drop growth make little difference
      to the final drop-size distribution. The rate of condensation per unit substrate
      area is especially high for the smallest drops and may help account for the high
      heat transfer rates associated with dropwise condensation relative to filmwise
      condensation in heat exchange applications.

PMID- 17014130
TI  - Surface structure smoothing effect of polysaccharide on a heat-set protein
      particle gel.
AB  - This work investigates surface properties of a protein particle gel and effects
      of polysaccharide on the surface microstructure of such a protein gel. Whey
      protein isolate (WPI) was used as the primary gelling agent, and a polysaccharide
      (xanthan) was investigated for its surface smoothing effects. The surface
      properties of heat-set WPI gels with and without the presence of xanthan (0,
      0.05, and 0.25%) were characterized using a surface friction technique. The
      surface friction force of a gel against a stainless steel substrate was found to
      be highly dependent on the sliding speed for all three gel samples, and the
      addition of xanthan caused a general reduction of surface friction. The gel
      containing no xanthan has the largest surface friction and behaved in the most
      load-dependent manner, whereas the gel containing 0.25% xanthan has the lowest
      surface friction and showed the least load dependency. It was inferred that the
      WPI gel containing no xanthan has the roughest surface among the three samples
      and the presence of xanthan leads to a smoother surface with probably a thinner
      layer of surface water. Surface features derived from surface friction tests were
      confirmed by surface microstructure observation from confocal laser scanning
      microscopy (CLSM) and environmental electron scanning microscopy (ESEM). Surface
      profiles from CLSM images were used to quantify the surface roughness of these
      gels. The mean square root surface roughness R(q) was calculated to be 3.8 +/-
      0.2, 3.0 +/- 0.2, and 1.5 +/- 0.2 microm for gels containing 0, 0.05, and 0.25%
      xanthan, respectively. The dual excitation images of protein and xanthan from
      CLSM observation and images from ESEM observation indicate a xanthan-rich layer
      at the surfaces of the xanthan-containing gel samples. We speculate that the
      creation of the outer surface of a particle gel is based on a different particle
      aggregation mechanism from that leading to network formation in the bulk.

PMID- 17014131
TI  - Lactobionamide surfactants with hydrogenated, perfluorinated or hemifluorinated
      tails: physical-chemical and biochemical characterization.
AB  - Detergents are customarily used to solubilize cell membranes and keep membrane
      proteins soluble in aqueous buffers, but they often lead to irreversible protein
      inactivation. Hemifluorinated amphiphiles with hybrid hydrophobic chains have
      been specifically designed to minimize the denaturating propensity of surfactants
      toward membrane proteins. We have studied the physical-chemical and biochemical
      properties of lactobionamide surfactants bearing either a hydrogenated, a
      fluorinated or a hemifluorinated chain (respectively H-, F-, and HF-Lac). We show
      that the dual composition of the hydrophobic chain of HF-Lac endows it with
      unusual physical-chemical properties as regards its critical micellar
      concentration, interfacial area per molecule, and behavior upon reverse phase
      chromatography. Analytical ultracentrifugation shows that, whereas H-Lac
      assembles into well-defined micelles, F-Lac and HF-Lac form large and
      heterogeneous assemblies, whose size increases with surfactant concentration.
      Molecular dynamics calculations suggest that F-Lac forms cylindrical micelles.
      The ability of HF-Lac to keep membrane proteins soluble was examined using the
      cytochrome b(6) f complex from Chlamydomonas reinhardtii's chloroplast as a model
      protein. HF-Lac/b(6) f complexes form particles relatively homogeneous in size,
      in which the b(6) f complex is as stable or markedly more stable, depending on
      the surfactant concentration, than it is in equivalent concentrations of
      hydrogenated surfactants, including H-Lac.

PMID- 17014132
TI  - Assembly of multilayer films incorporating a viral protein cage architecture.
AB  - Protein cage architectures such as viral capsids, heat shock proteins, ferritins,
      and DNA-binding proteins are nanoscale modular subunits that can be used to
      expand the structural and functional range of composite materials. Here, layer-by
      layer (LbL) assembly was used to incorporate cowpea chlorotic mottle virus (CCMV)
      into multilayer films. Three types of multilayer films were prepared. In the
      first type, ionic interactions were employed to assemble CCMV into triple layers.
      In the second type, complementary biological interactions (streptavidin/biotin)
      were used for this purpose. In a third variation of LbL assembly, complementary
      biological interactions were employed to produce nanotextured films that exhibit
      in-plane order over a micron scale without the need to adsorb onto a prepatterned
      template.

PMID- 17014133
TI  - Mechanical properties of interfacial films formed by lysozyme self-assembly at
      the air-water interface.
AB  - We present the first characterization of the mechanical properties of lysozyme
      films formed by self-assembly at the air-water interface using the Cambridge
      interfacial tensiometer (CIT), an apparatus capable of subjecting protein films
      to a much higher level of extensional strain than traditional dilatational
      techniques. CIT analysis, which is insensitive to surface pressure, provides a
      direct measure of the extensional stress-strain behavior of an interfacial film
      without the need to assume a mechanical model (e.g., viscoelastic), and without
      requiring difficult-to-test assumptions regarding low-strain material linearity.
      This testing method has revealed that the bulk solution pH from which assembly of
      an interfacial lysozyme film occurs influences the mechanical properties of the
      film more significantly than is suggested by the observed differences in elastic
      moduli or surface pressure. We have also identified a previously undescribed pH
      dependency in the effect of solution ionic strength on the mechanical strength of
      the lysozyme films formed at the air-water interface. Increasing solution ionic
      strength was found to increase lysozyme film strength when assembly occurred at
      pH 7, but it caused a decrease in film strength at pH 11, close to the pI of
      lysozyme. This result is discussed in terms of the significant contribution made
      to protein film strength by both electrostatic interactions and the hydrophobic
      effect. Washout experiments to remove protein from the bulk phase have shown that
      a small percentage of the interfacially adsorbed lysozyme molecules are
      reversibly adsorbed. Finally, the washout tests have probed the role played by
      additional adsorption to the fresh interface formed by the application of a large
      strain to the lysozyme film and have suggested the movement of reversibly bound
      lysozyme molecules from a subinterfacial layer to the interface.

PMID- 17014134
TI  - Study of a heavy metal biosorption onto raw and chemically modified Sargassum sp.
      via spectroscopic and modeling analysis.
AB  - In this study, raw and formaldehyde-modified Sargassum sp. are used for heavy
      metal removal. A series of experiments shows that the chemical modification by
      formaldehyde improves biosorption capacity by approximately 20%. Solution pH
      plays an important role in the metal uptake. According to X-ray photoelectron
      spectroscopic and Fourier transform infrared spectroscopic analysis, the possible
      organic functional groups in the metal binding include carboxyl, ether,
      alcoholic, hydroxyl, and amino functional groups. A new model that includes a
      series of coordination reactions among a generalized functional group, alkaline
      earth metal ions and heavy metal ions, is developed for simulation of biosorption
      process. The model well describes the single- and multiple-species metal
      biosorption process under different conditions such as pH. The biosorption of
      heavy metals is due to the ion exchange between the heavy metals and alkaline
      earth metals and their adsorption onto the free sites of the seaweeds. Slightly
      more than half of the metal uptake is due to ion exchange. The metal affinity for
      the functional groups follows a descending order of lead > copper > alkaline
      earth metal.

PMID- 17014135
TI  - Zirconia nanoparticles enhanced grafted collagen tri-helix scaffold for
      unmediated biosensing of hydrogen peroxide.
AB  - A novel, biocompatible, thermally steady, and nontoxic zirconia enhanced grafted
      collagen tri-helix scaffold was prepared on a graphite electrode. This scaffold
      provided a microenvironment for loading biomolecules and helped to retain their
      natural structure. UV-vis spectroscopy and scanning electron microscopy were used
      to characterize the scaffold and the structure of immobilized biomolecules. Using
      horseradish peroxidase (HRP) as an example, this scaffold accelerated its
      electron transfer and led to its direct electrochemical behavior with a good
      thermal stability up to 80 degrees C. The surface electron-transfer rate constant
      of the immobilized HRP was (5.55 +/- 0.43) s(-)(1) in 0.1 M pH 7.0 PBS at 18
      degrees C. The immobilized HRP showed an electrocatalytic activity to the
      reduction of hydrogen peroxide (H(2)O(2)) without aid of an electron mediator.
      The linear response range of the biosensor for H(2)O(2) was from 1.0 to 73.0
      microM with a correlation coefficient of 0.999 (n = 14), a limit of detection
      down to 0.25 microM and an apparent Michaelis-Menten constant of (0.28 +/- 0.02)
      mM. The biosensor exhibited high sensitivity, acceptable stability, and
      reproducibility. The ZrO(2) grafted collagen provided an excellent matrix for
      protein immobilization and biosensor preparation.

PMID- 17014136
TI  - Modeling of protein interactions with surface-grafted charged polymers.
      Correlations between statistical molecular modeling and a mean field approach.
AB  - Ion exchange media involving charge groups attached to flexible polymers are
      widely used for protein purification. Such media often provide enhanced target
      protein purity and yield. Yet, little is understood about protein interaction
      with such media at the molecular level, or how different media architectures
      might affect separation performance. To gain a better understanding of such
      adsorptive systems, statistical mechanical perturbation calculations, utilizing a
      Debye-Huckel potential, were performed on surface-grafted charged polymers and
      their interaction with model proteins. The studied systems were weakly charged,
      and the polymers were linear and relatively short (degree of polymerization is
      30). Segment distributions from the surface were also determined. The interaction
      of spherical model protein particles of 12-30 A radius were investigated with
      respect to polymer grafting density, distance from matrix surface, protein
      charge, and ionic strength. The partitioning coefficient of the model proteins
      was determined for different distances from the surface. An empirical mean field
      theory that scales the entropy of the protein with the square of the protein
      radius correlates well to Monte Carlo statistical modeling results. Upon
      adsorption to the polymer layers, the model proteins exhibit a critical surface
      charge density that is proportional to the ionic strength, independent of the
      grafting density, and appears to be a fundamental determinant of protein
      adsorption. Partitioning of protein-like nanoparticles to the charged polymer
      surface is only favored above the particle critical charge density.

PMID- 17014137
TI  - Unraveling the spatial distribution of immunoglobulins, enzymes, and
      polyelectrolytes within layer-by-layer self-assembled multilayers. Ellipsometric
      studies.
AB  - The ellipsometric characterization of a layer-by-layer electrostatically self
      assembled multilayer of polyphenol oxidase and alkaline phosphatase with the
      polycation poly(dimethyldiallylammonium chloride) built on an immunologic layer
      formed by immunoglobulin G (IgG) and glucose oxidase-conjugated anti-IgG (IgG
      GOD) on glassy carbon is reported. The step-by-step evolution of the psi-Delta
      ellipsometric angles was followed during film growth. Two optical models, named
      the three-layer film model and reorganization film model, were employed and found
      suitable for ellipsometric data interpretation. A comparative analysis of film
      optical properties, film thickness, and ellipsometric mass assessed from both
      models is also presented.

PMID- 17014138
TI  - Xerogel from N,N'-bis(2-phosphonoethyl)-1,4,5,8-naphthalenediimide: a nanohybrid
      material displaying efficient tryptophan photooxidation.
AB  - A nanohybrid xerogel (XDPN) was obtained from a tetraethyl orthosilicate (TEOS)
      condensation reaction in the presence of N,N'-bis(2-phosphonoethyl)-1,4,5,8
      naphthalenediimide (DPN). Physical and chemical characterization of the materials
      revealed that the XDPN morphology is quite different from that of xerogel without
      DPN (X). Photochemical and photophysical studies of the hybrid material showed
      that XDPN is efficient in promoting the photosensitization of tryptophan radical
      formation, and the radical species are stabilized due to the presence of DPN
      aggregates in the material. Radical stabilization can also be observed for DPN in
      solution but only for concentrations in the millimolar range.

PMID- 17014139
TI  - Carbide-derived carbons: a comparative study of porosity based on small-angle
      scattering and adsorption isotherms.
AB  - Porous carbons have received much attention recently for potential applications
      in energy generation and storage, molecular sieving, and environmental
      remediation. Property optimization for specific applications rests largely on
      controlling the volume, size, and shape of the pores at the synthetic level.
      Direct atom-scale experiments which might accurately and reliably measure these
      quantities are problematic, so indirect methods such as gas sorption are
      generally employed. Here we apply a second indirect method, small-angle X-ray
      scattering (SAXS), to study porosity in carbide-derived carbons (CDC). The
      results qualitatively confirm and reinforce model-dependent conclusions drawn
      from gas sorption isotherms. In particular, both techniques indicate the onset of
      broad polydispersity under the same processing conditions for particular porous
      carbon materials.

PMID- 17014140
TI  - Drug nanoparticles by antisolvent precipitation: mixing energy versus surfactant
      stabilization.
AB  - Organic itraconazole (ITZ) solutions were mixed with aqueous solutions to
      precipitate sub-300 nm particles over a wide range of energy dissipation rates,
      even for drug loadings as high as 86% (ITZ weight/total weight). The small
      particle sizes were produced with the stabilizer poloxamer 407, which lowered the
      interfacial tension, increasing the nucleation rate while inhibiting growth by
      coagulation and condensation. The highest nucleation rates and slowest growth
      rates were found at temperatures below 20 degrees C and increased with surfactant
      concentration and Reynolds number (Re). This increase in the time scale for
      growth reduced the Damkohler number (Da) (mixing time/precipitation time) to low
      values even for modest mixing energies. As the stabilizer concentration
      increased, the average particle size decreased and reached a threshold where Da
      may be considered to be unity. Da was maintained at a low value by compensating
      for a change in one variable away from optimum conditions (for small particles)
      by manipulating another variable. This tradeoff in compensation variables was
      demonstrated for organic flow rate vs Re, Re vs stabilizer concentration,
      stabilizer feed location (organic phase vs aqueous phase) vs stabilizer
      concentration, and stabilizer feed location vs Re. A decrease in the nucleation
      rate with particle density in the aqueous suspension indicated that secondary
      nucleation was minimal. A fundamental understanding of particle size control in
      antisolvent precipitation is beneficial for designing mixing systems and
      surfactant stabilizers for forming nanoparticles of poorly water soluble drugs
      with the potential for high dissolution rates.

PMID- 17014141
TI  - Encapsulation and selective recognition of molecularly imprinted theophylline and
      17beta-estradiol nanoparticles within electrospun polymer nanofibers.
AB  - Molecularly imprinted nanoparticles are cross-linked polymer colloids containing
      tailor-made molecular recognition sites. In this study, molecularly imprinted
      nanoparticles were easily encapsulated within polymer nanofibers using an
      electrospinning technique to produce a new type of molecular recognition
      material. Poly(ethylene terephthalate) (PET) was used as the supporting
      nanofibers matrix to encapsulate theophylline and 17beta-estradiol imprinted
      nanoparticles. The composite nanofibers had an average diameter of 150-300 nm,
      depending on the content of molecularly imprinted nanoparticles. For the
      theophylline and 17beta-estradiol imprinted polymers, an optimal loading of
      molecularly imprinted nanoparticles was 25-37.5 wt % based on PET. The composite
      nanofibers prepared under these conditions had a well-defined morphology and
      displayed the best selective target recognition. Our approach of electrospinning
      for-molecularly imprinted nanoparticles-encapsulation has unique advantages and
      opens new application opportunities for molecularly imprinted nanoparticles and
      electrospun nanofibers.

PMID- 17014142
TI  - Effect of supercritical CO2 in modified polystyrene 3D latex arrays.
AB  - The effect of supercritical CO(2) (scCO(2)) in 3D latex arrays formed by
      monodispersed particles of polystyrene (PS), PS cross-linked with divinylbenzene
      (PS-DVB), and PS block copolymers with 2-hydroxyethyl methacrylate (PS-HEMA),
      methacrylic acid (PS-MA), acrylic acid (PS-AA), itaconic acid (PS-IA), and a
      mixture of methacrylic and itaconic acid (PS-IA-MA) has been studied. Sorption of
      CO(2) into the polymer particles leads to a decrease in the glass transition
      temperature of the polymer and the swelling of the particles and induces their
      coalescence. 3D-latex arrays of the former compositions were treated in scCO(2)
      at temperatures and pressures ranging from 40 to 80 degrees C and from 85 to 197
      bar, respectively. The effect of CO(2) on the polymeric template was assessed by
      scanning electron microscopy and N(2) adsorption analysis. Bare PS and PS-HEMA
      particles sintered readily in scCO(2) at 40 degrees C and 85 bar. On the other
      hand, particles containing carboxylic acid groups on their surface (PS-MA, PS-AA,
      PS-IA, and PS-IA-MA) were, at the same temperature and pressure, more resistant
      to the CO(2) treatment. For a given polymer composition, the sorption of CO(2)
      inside the polymer particles, the swelling, and the degree of coalescence depend
      on the pressure, temperature, and time of the CO(2) treatment. Analysis of the
      pore size distributions from the N(2) adsorption data has allowed us to quantify
      the degree of coalescence of the particles in the matrix. By careful control of
      the experimental variables, the coalescence of the 3D latex array could be finely
      tuned using CO(2).

PMID- 17014143
TI  - In situ investigation of complex BaSO4 fiber generation in the presence of sodium
      polyacrylate. 1. Kinetics and solution analysis.
AB  - Simple solution analysis of the formation mechanism of complex BaSO(4) fiber
      bundles in the presence of polyacrylate sodium salt, via a bioinspired approach,
      is reported. Titration of the polyacrylate solution with Ba(2+) revealed complex
      formation and the optimum ratio of Ba(2+) to polyacrylate for a slow polymer
      controlled mineralization process. This is a much simpler and faster method to
      determine the appropriate additive/mineral concentration pairs as opposed to more
      common crystallization experiments in which the additive/mineral concentration is
      varied. Time-dependent pH measurements were carried out to determine the
      concentration of solution species from which BaSO(4) supersaturation throughout
      the fiber formation process can be calculated and the second-order kinetics of
      the Ba(2+) concentration in solution can be identified. Conductivity
      measurements, pH measurements, and analytical ultracentrifugation revealed the
      first formed species to be Ba-polyacrylate complexes. A combination of the
      solution analysis results and optical microscopic images allows a detailed
      picture of the complex precipitation and self-organization process, a particle
      mediated process involving mesoscopic transformations, to be revealed.

PMID- 17014144
TI  - In situ investigation of complex BaSO4 fiber generation in the presence of sodium
      polyacrylate. 2. Crystallization mechanisms.
AB  - The formation mechanisms of complex BaSO(4) fiber bundles and cones in the
      presence of polyacrylate sodium salt via a bioinspired approach at ambient
      temperature in an aqueous environment are reported. These complex organic
      inorganic hybrid structures assemble after heterogeneous nucleation of amorphous
      precursor particle aggregates on polar surfaces, and the crystallization area can
      be patterned. In contrast to earlier reports, three different mechanisms based on
      the oriented attachment of nanoparticles were revealed for the formation of
      typical fibrous superstructures depending on the supersaturation or on the number
      of precursor particles. (A) High supersaturation (S > 2): large amorphous
      aggregates stick to a polar surface, form fiber bundles after mesoscopic
      transformation and oriented attachment, and then form a narrow tip through
      polymer interaction. (B) Low supersaturation (S = 1.02-2): only a few fibers
      nucleate heterogeneously from a single nucleation spot, and amorphous particles
      stick to existing fibers, which results in the formation of a fiber bundle. (C)
      Vanishing supersaturation (S = 1-1.02): nucleation of a fiber bundle from a
      single nucleation spot with self-limiting repetitive growth as a result of the
      limited amount of building material. These growth processes are supported by time
      resolved optical microscopy in solution, TEM, SEM, and DLS.

PMID- 17014145
TI  - Optical second-harmonic generation study of exfoliated MoS2-malachite green
      inclusion materials.
AB  - We have examined the properties of exfoliated and restacked MoS(2)-malachite
      green (MG) inclusion compounds to provide insight into the MG-MoS(2) interactions
      that characterize these materials. The results of X-ray diffraction experiments
      indicate that MG included into the restacked structure adopts a flat orientation
      approximately parallel to the MoS(2) sheets. Second-harmonic generation
      experiments conducted on the exfoliated and restacked materials provide
      information regarding the averaged orientation of the MG. At low MG coverage, our
      results support the X-ray diffraction findings, and yield large averaged
      orientation angles, consistent with a flat orientation of MG between the MoS(2)
      layers. However, as the MG coverage is increased, the SHG results indicate
      averaged MG orientations that are much more upright, consistent with the
      expulsion of excess MG from the layers to the outside of the restacked
      crystallites. Together with X-ray diffraction and adsorption isotherm data, our
      SHG results provide a model for the exfoliation, adsorption, and subsequent
      restacking of these MG-based inclusion materials and demonstrate the utility of
      nonlinear optical techniques as probes of these interesting layered structures.

PMID- 17014146
TI  - Fabrication and characterization of multilayer films from amphiphilic poly(p
      phenylene)s.
AB  - Over the past two decades, considerable efforts have been devoted to the
      development of conjugated polymeric materials for electronic applications due to
      the tunability of their properties through variation of their chemical structure.
      The LB technique is one of the most effective and precise methods for controlling
      the organization and thereby the properties of polymer films at the nanoscale for
      device fabrication. A detailed study was performed on the Langmuir-Schaefer (LS)
      monolayer and Langmuir-Blodgett-Kuhn (LBK) multilayer formation of newly designed
      conjugated poly(p-phenylene)s (C(n)PPPOH), incorporated with alkoxy groups with
      different chain lengths (C(6)H(13)O-, C(12)H(25)O-, and C(18)H(37)O-) and
      hydroxyl groups on the polymer backbone. The monolayer formed at the air-water
      interface was characterized using surface pressure-area isotherms, including
      hysteresis measurements. The films were then transferred to different hydrophilic
      solid substrates and analyzed using surface plasmon resonance spectroscopy, UV
      vis spectroscopy, fluorescence spectroscopy, and AFM measurements. The results
      showed that the polymer with a short alkoxy chain (C(6)PPPOH) forms uniform
      monolayers at the air-water interface and can be transferred as multilayer films
      compared to C(12)PPPOH and C(18)PPPOH. The observed film thicknesses measured by
      SPR and AFM studies were similar to the theoretical value obtained in the case of
      C(6)PPPOH, whereas this was not the case with the other two polymers. The present
      study shows that the polymer C(n)PPPOH with short alkoxy chain can be transferred
      onto different solid substrates for device fabrication with molecular level
      control.

PMID- 17014147
TI  - Degradation of the pesticide fenitrothion as mediated by cationic surfactants and
      alpha-nucleophilic reagents.
AB  - The reaction of fenitrothion with a series of alpha-nucleophile oximates having
      pK(a) values in the range of 7.7-11.8 was studied both in the absence and
      presence of cetyltrimethylammonium (CTA(+)) surfactants. Reaction with CTA
      oximates was found to proceed through two pathways: S(N)2(P) and S(N)2(C); an
      S(N)Ar pathway was not observed. Accordingly, the observed rate constants were
      dissected into the two corresponding S(N)2(P) and S(N)2(C) pathways. Use of the
      pseudophase ion exchange (PPIE) model for micellar catalysis in the CTA(+) system
      allowed evaluation of micellar second-order rate constant (k(2m)) parameters and
      binding constants, (K(S)). K(S) values for CTA-oximates were found to vary with
      the counterion, and the rate enhancement depended on a combination of K(S) and
      k(2m) values. k(2m)/k(2w) values ranged from 0.0025 to 0.64, suggesting that a
      concentration effect is mainly responsible for the rate enhancement. In the
      absence of surfactant, an alpha-effect (i.e., k(alpha)/k(normal)) varying from 8
      to 450 was observed for the oximate reaction, decreasing with increasing pK(a).
      It is proposed that differential solvation (transition-state imbalance) is a
      cause of the alpha-effect in this system.

PMID- 17014148
TI  - Hydrophilic composite elastomeric mold for high-resolution soft lithography.
AB  - Here, we introduce a nanopatternable hydrophilic composite elastomer highly
      desirable for both nanostructure patterning via solvent-assisted micromolding
      (SAMIM) and microcontact printing of polar inks. This composite precursor is
      prepared by blending two UV-curable materials, Norland Optical Adhesives (NOA) 63
      and poly(ethylene glycol) diacrylate (PEGDA), in an appropriate ratio; upon UV
      polymerization, a nanopatternable elastomer with preferential permeability both
      to aqueous and organic solvent is fabricated. Using this composite mold,
      nanoscale SAMIM of poly(4-vinylpyridine) (P4VP) and microcontact printing of a
      polar biomolecule, bovine serum albumin (BSA), was successfully demonstrated,
      paving the way for facile and efficient reproduction of various nanopatterns and
      a biomolecule-printed array platform.

PMID- 17014149
TI  - Characterization of thermally sensitive interactions in aqueous mixtures of
      hydrophobically modified hydroxyethylcellulose and cyclodextrins.
AB  - Effects of beta-cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP
      beta-CD) addition and temperature on thermodynamic, rheological, and structural
      features of semidilute solutions of hydroxyethylcellulose (HEC) and its
      hydrophobically modified analogue (HM-HEC) are reported. Differential scanning
      calorimetric (DSC) measurements revealed a thermally induced crystal melting
      transition of beta-CD at high concentrations in solutions of HEC and HM-HEC. No
      transition with HP-beta-CD was observed in aqueous solution. Viscosity results
      indicated that at a cosolute concentration of 2 mm, the beta-CD units are
      threaded onto hydrophobic tails of HM-HEC (C16 groups) to form columnar
      structures. This arrangement is more effective in the encapsulation of the
      hydrophobic chains than the monomer hydrophobic deactivation accomplished by the
      HP-beta-CD units. At cosolute concentrations above 8 mm, no further decoupling of
      the hydrophobic interactions occurs for any of the cosolutes. Small-angle neutron
      scattering (SANS) experiments on HM-HEC/beta-CD mixtures suggest that the large
      scale association structures in HM-HEC/D(2)O solutions are reduced upon addition
      of beta-CD, and an interesting temperature effect is observed at 2 mm beta-CD
      addition. At high beta-CD concentrations and low temperatures, the formation of
      large beta-CD clusters or crystallites generates cross-links in the HEC and HM
      HEC networks, resulting in a viscosity enhancement of several orders of
      magnitude. This strong temperature effect is not reflected in the structural
      features probed by SANS.

PMID- 17014150
TI  - Reversible electrowetting of vertically aligned superhydrophobic carbon
      nanofibers.
AB  - Reversible electrostatically induced wetting (electrowetting) of vertically
      aligned superhydrophobic carbon nanofibers has been investigated. Carbon
      nanofibers on a 5 x 5 microm pitch were grown on Si substrates, electrically
      insulated with a conformal dielectric, and hydrophobized with fluoropolymer. This
      nanostructured scaffold exhibited superhydrophobic behavior for saline (theta
      approximately 160 degrees). Electrowetting induced a contact angle reduction to
      theta approximately 100 degrees. Competitive two-liquid (dodecane/saline)
      electrowetting exhibited reversibility on the same nanostructured scaffold.
      Without applied bias, ultra-fine-point tip (approximately 25 nm radius)
      nanofibers result in effectively zero capacitance with the overlying saline
      layer. Complete electrowetting of the substrate is confirmed as capacitance
      values increase by several orders of magnitude with increased wetting. These
      results demonstrate the applicability of reversible electrowetting on
      nanostructured scaffolds and use of nanofabricated structures that can be
      integrated with various micro- and nanoelectronic technologies.

PMID- 17014151
TI  - Nanoscale tubular vessels for storage of methane at ambient temperatures.
AB  - Novel carbon nanostructures can serve as effective storage media for methane, a
      source of "clean energy" for the future. We have used Grand Canonical Monte Carlo
      Simulation for the modeling of methane storage at 293 K and pressures up to 80
      MPa in idealized bundles of (10,10) armchair-type single-walled carbon nanotubes
      and wormlike carbon pores. We have found that these carbon nanomaterials can be
      treated as the world's smallest high-capacity methane storage vessels. Our
      simulation results indicate that such novel carbon nanostructures can reach a
      high volumetric energy storage, exceeding the US FreedomCAR Partnership target of
      2010 (5.4 MJ dm(-3)), at low to moderate pressures ranging from 1 to 7 MPa at 293
      K. On the contrary, in the absence of these nanomaterials, methane needs to be
      compressed to approximately 13 MPa at 293 K to achieve the same target. The light
      carbon membranes composed of bundles of single-walled carbon nanotubes or
      wormlike pores efficiently physisorb methane at low to moderate pressures at 293
      K, which we believe should be particularly important for automobiles and
      stationary devices. However, above 15-20 MPa at 293 K, all investigated samples
      of novel carbon nanomaterials are not as effective when compared with compression
      alone since the stored volumetric energy and power saturate at values below those
      of the bulk, compressed fluid.

PMID- 17014152
TI  - Hierarchical multiscale simulation of electrokinetic transport in silica
      nanochannels at the point of zero charge.
AB  - Effects of nanoscale confinement and partial charges that stem from quantum
      calculations are investigated in silica slit channels filled with 1 M KCl at the
      point of zero charge by using a hierarchical multiscale simulation methodology.
      Partial charges of both bulk and surface atoms from ab initio quantum
      calculations that take into account bond polarization and electronegativity are
      used in molecular dynamics (MD) simulations to obtain ion and water concentration
      profiles for channel widths of 1.1, 2.1, 2.75, and 4.1 nm. The interfacial
      electron density profiles of simulations matched well with that of recent X-ray
      reflectivity experiments. By simulating corresponding channels with no partial
      charges, it was observed that the partial charges affect the concentration
      profiles and transport properties such as diffusion coefficients and mobilities
      up to a distance of about 3 sigma(O)(-)(O) from the surface. Both in uncharged
      and partially charged cases, oscillations in concentration profiles of K(+) and
      Cl(-) ions give rise to an electro-osmotic flow in the presence of an external
      electric field, indicating the presence of an electric double layer at net zero
      surface charge, contrary to the expectations from classical continuum theory. I-V
      curves in a channel-bath system using ionic mobilities from MD simulations were
      significantly different for channels with and without partial charges for channel
      widths less than 4.1 nm.

PMID- 17014153
TI  - Stable jets of viscoelastic fluids and self-assembled cylindrical capsules by
      hydrodynamic focusing.
AB  - We demonstrate formation of long-lived cylindrical jets of a viscoelastic fluid
      using hydrodynamic focusing. A solution of polyacrylamide in water is driven
      coaxially with immiscible oil and subjected to strong extensional flow. At high
      flow rates, the aqueous phase forms jets that are 4-90 microm in diameter and
      several centimeters long. The liquid surfaces of these jets are then used as
      templates for assembly of microspheres into novel rigid and hollow cylinders.

PMID- 17014154
TI  - Fabrication of arrays of sub-20-nm silica walls via photolithography and solution
      based molecular coating.
AB  - We report herein fabrication of arrays of sub-20-nm silica walls via
      photolithography and the surface sol-gel process. A photolithographically
      fabricated line template on a silicon wafer was coated with a silica nanolayer
      using the surface sol-gel process, and then the topmost portion of the silica
      layer and the template were successively removed using CHF(3) and oxygen plasma,
      respectively, leaving the sidewalls of the silica layers remaining on the
      substrate. These walls were fully self-supporting, and the thicknesses of silica
      wall were 6, 8, and 12 nm at 20, 30, and 60 cycles, respectively. The
      height/width ratio of the wall was 38 at the 30-cycle coating. This ratio is
      surprisingly high when compared to that of the conventional photolithography
      processes. Successive formation of the silica, polymer, and silica layers yielded
      a trilayer sidewall, and the spacer polymer layer could be selectively removed to
      form a doubled sidewall. Size reduction and proliferation of sub-20-nm silica
      wall was thus achieved. The reported method is simple and cost-efficient and
      opens a gateway to further miniaturization of nanostructures.

PMID- 17014155
TI  - Measurements of interface stress of silicon dioxide in contact with water-phenol
      mixtures by bending of microcantilevers.
AB  - We use the bending of silicon microcantilevers to measure changes in mechanical
      stress at interfaces between phenol-water mixtures and SiO(2). The curvature of
      the microcantilever is measured by an optical system that combines a rapidly
      scanning laser beam, a position-sensitive detector, and lock-in detection to
      achieve a long-time stability on the order of 6 mN m(-1) over 4 h and a short
      time sensitivity of better than 1 mN m(-1). Thermally oxidized Si shows the
      smallest changes in interface stress as a function of phenol concentration in
      water. For hydrophilic SiO(2) prepared by chemical treatment, the change in
      interface stress at 5 wt % phenol in water is larger than that of thermally
      oxidized Si by -60 mN m(-1); for SiO(2) formed by exposure of the silicon
      microcantilever to ozone, the change in surface stress is larger than that of
      thermally oxidized Si by -330 mN m(-1).

PMID- 17014156
TI  - Continuous glucose detection using boronic acid-substituted viologens in
      fluorescent hydrogels: linker effects and extension to fiber optics.
AB  - A fluorescent anionic dye and a viologen appended with boronic acids, which serve
      as glucose receptors, have been synthesized and immobilized into a poly(2
      hydroxyethyl methacrylate) hydrogel for use as a continuous glucose monitor. The
      fluorescence of the dye is modulated by the quenching efficiency of the viologen
      based receptor, which in turn is dependent on the glucose concentration. Two
      monomeric versions of the quencher/receptor unit were prepared and their
      performance within the hydrogel evaluated. By tethering the quencher/receptor to
      the hydrogel matrix using a single-point attachment, slightly improved glucose
      sensing was observed. The hydrogels were tested for their ability to continuously
      and reversibly detect glucose over the course of several hours. The tests were
      carried out using a cuvette-based system, as well as a fiber-optic-based
      configuration. Under physiological conditions (0.1 M phosphate buffer, pH 7.4, 37
      degrees C), the fluorescent hydrogels display an excellent dynamic response to
      glucose concentrations within the biologically significant range (2.5-20 mM).

PMID- 17014157
TI  - Two-color reduced-Doppler ion imaging.
AB  - We demonstrate a two-color reduced-Doppler probe for ion imaging that, in many
      applications, offers advantages over conventional 2+1 resonance-enhanced
      multiphoton ionization detection. Using counterpropagating beams of two different
      colors, one of which is broadband 266 nm, we achieve convenient and sensitive D
      atom detection without the need for Doppler scanning. We demonstrate the approach
      using 224 nm photodissociation of DBr. This method improves the sensitivity and
      signal-to-noise ratio and presents advantages and opportunities for use in the
      other systems.

PMID- 17014158
TI  - Size-dependent alternation of magnetoresistive properties in atomic chains.
AB  - Spin-polarized electronic and transport properties of carbon atomic chains are
      investigated when they are capped with magnetic transition-metal (TM) atoms like
      Cr or Co. The magnetic ground state of the TM-C(n)-TM chains alternates between
      the ferromagnetic (F) and antiferromagnetic (AF) spin configurations as a
      function of n. In view of the nanoscale spintronic device applications the
      desirable AF state is obtained for only even-n chains with Cr; conversely only
      odd-n chains with Co have AF ground states. When connected to appropriate
      metallic electrodes these atomic chains display a strong spin-valve effect.
      Analysis of structural, electronic, and magnetic properties of these atomic
      chains, as well as the indirect exchange coupling of the TM atoms through non
      magnetic carbon atoms are presented.

PMID- 17014159
TI  - Second-order overtone and combination modes in the LOLA region of acid treated
      double-walled carbon nanotubes.
AB  - Moderate acid treatment of double-walled carbon nanotubes (DWCNTs) has given rise
      to two new experimentally observed second-order double resonant Raman scattering
      frequencies centered at 1901 cm(-1) and 1942 cm(-1), in the highly dispersive
      LOLA region. These LOLA overtones and combination modes have been predicted by
      double resonance theory for two phonons associated with the K- and Gamma-points,
      respectively.

PMID- 17014160
TI  - Excitation energies through the locally renormalized equation-of-motion
      formalism: singles and doubles model.
AB  - The stationary conditions obtained from approximate coupled-cluster functional
      derived from the numerator-denominator connected expansion (NDC) [K. Kowalski and
      P. Piecuch, J. Chem. Phys. 122, 074107 (2005)] are employed to calculate the
      linear response of cluster amplitudes. A simple scheme that involves singly and
      doubly excited amplitudes, termed locally renormalized equation-of-motion
      approach with singles and doubles (LR-EOMCCSD), is compared with other excited
      state methods that include up to two-body operators in the wave function
      expansion. In particular, the impact of the local denominators on the excitation
      energies is discussed in detail. Several benchmark calculations on the CH(+),
      C(2), N(2), O(3), and ClOCl molecules are presented to illustrate the performance
      of the LR-EOMCCSD approach.

PMID- 17014161
TI  - A parametric variant of resonant activation: two-state model approach.
AB  - Mean first passage time of a periodically driven particle for its escape over a
      fluctuating barrier with wells remaining unbiased exhibits a resonance when the
      frequency of the driving field is varied. This parametric variant of resonant
      activation and associated features of noise induced transition are realized in
      terms of a two-state model to estimate analytically several quantifiers of the
      escape event. Numerical simulation on a continuous double-well model collaborates
      our theoretical analysis.

PMID- 17014162
TI  - Efficient and accurate solvation energy calculation from polarizable continuum
      models.
AB  - A new approach is proposed to enhance the efficiency and accuracy for calculation
      of the long-range electrostatic interaction from implicit solvation models, i.e.,
      the polarizable continuum model (PCM) and its variants, conductorlike
      PCM/conductorlike screening model and integral equation formalism PCM. In these
      methods the solvent electrostatics effects are represented by a set of discrete
      apparent charges distributed on tesserae of the molecular cavity surface
      embedding the solute. In principle, the accuracy of these methods is improved if
      the cavity surface is tessellated to finer tesserae; however, the computational
      time is increased rapidly. We show that such undesired dependency between
      accuracy and efficiency is a result of the inaccurate treatment of the apparent
      charge self-contribution to the potential and/or electric field. By taking into
      account the full effects due to the size and curvature of the segment occupied by
      each apparent charge, the error in calculated electrostatic solvation free energy
      is essentially zero for ions (point charge at the center of a sphere) regardless
      of the degree of tessellation used. For molecules where gradient of apparent
      charge density is nonzero at the cavity surface, we propose a multiple-sampling
      technique which significantly lowers the calculated error compared to the
      original PCM methods, especially when very few numbers of tesserae are used.

PMID- 17014163
TI  - Density functional theory of complex transition densities.
AB  - We present an extension of Hohenberg-Kohn-Sham density functional theory to the
      domain of complex local potentials and complex electron densities. The approach
      is applicable to resonance (Siegert) [Phys. Rev. 56, 750 (1939)] states and other
      scattering and transport problems that can be described by a normalized state of
      a Hamiltonian containing a complex local potential. Such Hamiltonians are non
      Hermitian and their eigenvalues are in general complex, the imaginary part being
      inversely proportional to the lifetime of the system. The one-to-one
      correspondence between complex local potentials nu and complex electron densities
      rho is established provided that the complex variables are sufficiently close to
      real local potentials and densities of nondegenerate ground states. We show that
      the exchange-correlation functionals, contributing to the complex energy, are
      determined through analytic continuation of their ground-state-theory
      counterparts. This implies that the exchange-correlation effects on the lifetime
      of a resonance are, under appropriate conditions, already determined by the
      functionals of the ground-state theory.

PMID- 17014164
TI  - On the short-time limit of ring polymer molecular dynamics.
AB  - We examine the short-time accuracy of a class of approximate quantum dynamical
      techniques that includes the centroid molecular dynamics (CMD) and ring polymer
      molecular dynamics (RPMD) methods. Both of these methods are based on the path
      integral molecular dynamics (PIMD) technique for calculating the exact static
      equilibrium properties of quantum mechanical systems. For Kubo-transformed real
      time correlation functions involving operators that are linear functions of
      positions or momenta, the RPMD and (adiabatic) CMD approximations differ only in
      the choice of the artificial mass matrix of the system of ring polymer beads that
      is employed in PIMD. The obvious ansatz for a general method of this type is
      therefore to regard the elements of the PIMD (or Parrinello-Rahman) mass matrix
      as an adjustable set of parameters that can be chosen to improve the accuracy of
      the resulting approximation. We show here that this ansatz leads uniquely to the
      RPMD approximation when the criterion that is used to select the mass matrix is
      the short-time accuracy of the Kubo-transformed correlation function. In
      particular, we show that the leading error in the RPMD position autocorrelation
      function is O(t(8)) and the error in the velocity autocorrelation function is
      O(t(6)), for a general anharmonic potential. The corresponding errors in the CMD
      approximation are O(t(6)) and O(t(4)), respectively.

PMID- 17014165
TI  - A variational approach to the stochastic aspects of cellular signal transduction.
AB  - Cellular signaling networks have evolved to cope with intrinsic fluctuations,
      coming from the small numbers of constituents, and the environmental noise.
      Stochastic chemical kinetics equations govern the way biochemical networks
      process noisy signals. The essential difficulty associated with the master
      equation approach to solving the stochastic chemical kinetics problem is the
      enormous number of ordinary differential equations involved. In this work, we
      show how to achieve tremendous reduction in the dimensionality of specific
      reaction cascade dynamics by solving variationally an equivalent quantum field
      theoretic formulation of stochastic chemical kinetics. The present formulation
      avoids cumbersome commutator computations in the derivation of evolution
      equations, making the physical significance of the variational method more
      transparent. We propose novel time-dependent basis functions which work well over
      a wide range of rate parameters. We apply the new basis functions to describe
      stochastic signaling in several enzymatic cascades and compare the results so
      obtained with those from alternative solution techniques. The variational Ansatz
      gives probability distributions that agree well with the exact ones, even when
      fluctuations are large and discreteness and nonlinearity are important. A
      numerical implementation of our technique is many orders of magnitude more
      efficient computationally compared with the traditional Monte Carlo simulation
      algorithms or the Langevin simulations.

PMID- 17014166
TI  - A localized orbital analysis of the thermochemical errors in hybrid density
      functional theory: achieving chemical accuracy via a simple empirical correction
      scheme.
AB  - This paper describes an empirical localized orbital correction model which
      improves the accuracy of density functional theory (DFT) methods for the
      prediction of thermochemical properties for molecules of first and second row
      elements. The B3LYP localized orbital correction version of the model improves
      B3LYP DFT atomization energy calculations on the G3 data set of 222 molecules
      from a mean absolute deviation (MAD) from experiment of 4.8 to 0.8 kcal/mol. The
      almost complete elimination of large outliers and the substantial reduction in
      MAD yield overall results comparable to the G3 wave-function-based method;
      furthermore, the new model has zero additional computational cost beyond standard
      DFT calculations. The following four classes of correction parameters are applied
      to a molecule based on standard valence bond assignments: corrections to atoms,
      corrections to individual bonds, corrections for neighboring bonds of a given
      bond, and radical environmental corrections. Although the model is heuristic and
      is based on a 22 parameter multiple linear regression to experimental errors,
      each of the parameters is justified on physical grounds, and each provides
      insight into the fundamental limitations of DFT, most importantly the failure of
      current DFT methods to accurately account for nondynamical electron correlation.

PMID- 17014167
TI  - Automatic generation of force fields and property surfaces for use in variational
      vibrational calculations of anharmonic vibrational energies and zero-point
      vibrational averaged properties.
AB  - An automatic and general procedure for the calculation of geometrical derivatives
      of the energy and general property surfaces for molecular systems is developed
      and implemented. General expressions for an n-mode representation are derived,
      where the n-mode representation includes only the couplings between n or less
      degrees of freedom. The general expressions are specialized to derivative force
      fields and property surfaces, and a scheme for calculation of the numerical
      derivatives is implemented. The implementation is interfaced to electronic
      structure programs and may be used for both ground and excited electronic states.
      The implementation is done in the context of a vibrational structure program and
      can be used in combination with vibrational self-consistent field (VSCF),
      vibrational configuration interaction (VCI), vibrational Moller-Plesset, and
      vibrational coupled cluster calculations of anharmonic wave functions and
      calculation of vibrational averaged properties at the VSCF and VCI levels. Sample
      calculations are presented for fundamental vibrational energies and vibrationally
      averaged dipole moments and frequency dependent polarizabilities and
      hyperpolarizabilities of water and formaldehyde.

PMID- 17014168
TI  - Rotranslational state-to-state rates and spectral representation of inelastic
      collisions in low-temperature molecular hydrogen.
AB  - Inelastic collisions in natural H2 are studied from the experimental and
      theoretical points of view between 10 and 140 K. Rotational populations and
      number densities measured by Raman spectroscopy along supersonic expansions of H2
      provide the link between experimental and theoretical rotranslational state-to
      state rate coefficients of H2 in the vibrational ground state. These rates are
      calculated in the close-scattering approach with the MOLSCAT code employing a
      recent ab initio H2-H2 potential. The calculated rates are assessed by means of a
      master equation describing the time evolution of the experimental rotational
      populations. The feasibility for obtaining the rates on the sole basis of the
      experiment is discussed. The dominant processes j(1)j(2)-->j'(1)j'(2) in the
      investigated thermal range are found to be 21-->01 >30-->12 >31-->11, proving the
      importance of double processes such as 30-->12. Good agreement is found between
      theory and experiment, as well as with earlier ultrasonic measurements of
      relaxation times. A spectral representation is proposed in order to visualize
      quantitatively the collisional contributions in any nonequilibrium time evolving
      process.

PMID- 17014169
TI  - Photodissociation of methane: exploring potential energy surfaces.
AB  - The potential energy surface for the first excited singlet state (S(1)) of
      methane is explored using multireference singles and doubles configuration
      interaction calculations, employing a valence triple zeta basis set. A larger
      valence quadruple zeta basis is used to calculate the vertical excitation energy
      and dissociation energies. All stationary points found on the S(1) surface are
      saddle points and have imaginary frequencies for symmetry-breaking vibrations. By
      studying several two-dimensional cuts through the potential energy surfaces, it
      is argued that CH(4) in the S(1) state will distort to planar structures. Several
      conical intersection seams between the ground state surface S(0) and the S(1)
      surface have been identified at planar geometries. The conical intersections
      provide electronically nonadiabatic pathways towards products
      CH(3)((approximately)X (2)A"(2))+H, CH(2)((approximately)a (1)A(1))+H(2), or
      CH(2)((approximately)X (3)B(1))+H+H. The present results thereby make it
      plausible that the CH(3)((approximately)X (2)A"(2))+H and CH(2)((approximately)a
      (1)A(1))+H(2) channels are major dissociation channels, as has been observed
      experimentally.

PMID- 17014170
TI  - Relative energy of the high-(5T2g) and low-(1A1g) spin states of [Fe(H2O)6]2+,
      [Fe(NH3)6]2+, and [Fe(bpy)3]2+: CASPT2 versus density functional theory.
AB  - High-level ab initio calculations using the CASPT2 method and extensive basis
      sets were performed on the energy differences of the high-[(5)T(2g):t(2g) (4)e(g)
      (2)] and low-[(1)A(1g):t(2g) (6)] spin states of the pseudo-octahedral Fe(II)
      complexes [Fe(H(2)O)(6)](2+), [Fe(NH(3))(6)](2+), and [Fe(bpy)(3)](2+). The
      results are compared to the results obtained from density functional theory
      calculations with the generalized gradient approximation functional BP86 and two
      hybrid functionals B3LYP and PBE0, and serve as a calibration for the latter
      methods. We find that large basis set CASPT2 calculations may provide results for
      the high-spin/low-spin splitting DeltaE(HL) that are accurate to within 1000 cm(
      1), provided they are based on an adequately large CAS[10,12] reference wave
      function. The latter condition was found to be much more stringent for
      [Fe(bpy)(3)](2+) than for the other two complexes. Our "best" results for
      DeltaE(HL) (including a zero-point energy correction) are -17 690 cm(-1) for
      [Fe(H(2)O)(6)](2+), -8389 cm(-1) for [Fe(NH(3))(6)](2+), and 3820 cm(-1) for
      [Fe(bpy)(3)](2+).

PMID- 17014172
TI  - Planar nitrogen-doped aluminum clusters AlxN- (x=3-5).
AB  - The electronic and geometrical structures of three nitrogen-doped aluminum
      clusters, Al(x)N(-) (x=3-5), are investigated using photoelectron spectroscopy
      and ab initio calculations. Well-resolved photoelectron spectra have been
      obtained for the nitrogen-doped aluminum clusters at four photon energies (532,
      355, 266, and 193 nm). Global minimum structure searches for Al(x)N(-) (x=3-5)
      and their corresponding neutrals are performed using several theoretical methods.
      Vertical electron detachment energies are calculated using three different
      methods for the lowest energy structures and low-lying isomers are compared with
      the experimental observations. Planar structures have been established for all
      the three Al(x)N(-) (x=3-5) anions from the joint experimental and theoretical
      studies. For Al(5)N(-), a low-lying nonplanar isomer is also found to contribute
      to the experimental spectra, signifying the onset of two-dimensional to three
      dimensional transition in nitrogen-doped aluminum clusters. The chemical bonding
      in all the planar clusters has been elucidated on the basis of molecular orbital
      and natural bond analyses.

PMID- 17014171
TI  - Intermolecular interactions of nitrobenzene-benzene complex and nitrobenzene
      dimer: significant stabilization of slipped-parallel orientation by dispersion
      interaction.
AB  - The CCSD(T) level interaction energies of eight orientations of nitrobenzene
      benzene complexes and nine orientations of nitrobenzene dimers at the basis set
      limit have been estimated. The calculated interaction energy of the most stable
      slipped-parallel (C(s)) nitrobenzene-benzene complex was -4.51 kcal/mol. That of
      the most stable slipped-parallel (antiparallel) (C(2h)) nitrobenzene dimer was 
      6.81 kcal/mol. The interaction energies of these complexes are significantly
      larger than that of the benzene dimer. The T-shaped complexes are substantially
      less stable. Although nitrobenzene has a polar nitro group, electrostatic
      interaction is always considerably weaker than the dispersion interaction. The
      dispersion interaction in these complexes is larger than that in the benzene
      dimer, which is the cause of the preference of the slipped-parallel orientation
      in these complexes.

PMID- 17014173
TI  - Electric dipole polarizabilities and C6 dipole-dipole dispersion coefficients for
      sodium clusters and C60.
AB  - The frequency-dependent polarizabilities of closed-shell sodium clusters
      containing up to 20 atoms have been calculated using the linear complex
      polarization propagator approach in conjunction with Hartree-Fock and Kohn-Sham
      density functional theories. In combination with polarizabilities for C(60) from
      a previous work [J. Chem. Phys. 123, 124312 (2005)], the C(6) dipole-dipole
      dispersion coefficients for the metal-cluster-to-cluster and cluster-to
      buckminster-fullerene interactions are obtained via the Casimir-Polder relation
      [Phys. Rev. 73, 360 (1948)]. The B3PW91 results for the polarizability of the
      sodium dimer and tetramer are benchmarked against coupled cluster calculations.
      The error bars of the reported theoretical results for the C(6) coefficients are
      estimated to be 5%, and the results are well within the error bars of the
      experiment.

PMID- 17014174
TI  - Three-dimensional potential energy surface of the Ar-OH(2Pi i) complex.
AB  - Pure rotational transitions in the ground state for Ar-OH and Ar-OD [Y. Ohshima
      et al., J. Chem. Phys. 95, 7001 (1991) and Y. Endo et al., Faraday Discuss. 97,
      341 (1994)], those in the excited states of the OH vibration, nu(s)=1 and 2,
      observed by Fourier-transform microwave spectroscopy in the present study,
      rotation-vibration transitions observed by infrared-ultraviolet double-resonance
      spectroscopy [K. M. Beck et al., Chem. Phys. Lett. 162, 203 (1989) and R. T. Bonn
      et al., J. Chem. Phys. 112, 4942 (2000)], and the P-level structure observed by
      stimulated emission pumping spectroscopy [M. T. Berry et al., Chem. Phys. Lett.
      178, 301 (1991)] have been simultaneously analyzed to determine the potential
      energy surface of Ar-OH in the ground state. A Schrodinger equation, considering
      all the freedom of motions for an atom-diatom system in the Jacobi coordinate, R,
      theta, and r, was numerically solved to obtain energies of the rovibrational
      energy levels using the discrete variable representation method. A three
      dimensional potential energy surface is determined by a least-squares fitting. In
      the analysis the potential parameters, obtained by ab initio calculations at the
      RCCSD(T) level of theory with a set of basis functions of aug-cc-pVTZ and midbond
      functions, are used as initial values. The determined intermolecular potential
      energy surface and its dependence on the OH monomer bond length are compared with
      those of an isovalent radical complex, Ar-SH.

PMID- 17014175
TI  - Progress in understanding the intramolecular vibrational redistribution dynamics
      in the S(1) state of para-fluorotoluene.
AB  - We employ zero-kinetic-energy (ZEKE) photoelectron spectroscopy with nanosecond
      laser pulses to study intramolecular vibrational redistribution (IVR) in S(1)
      para-fluorotoluene. The frequency resolution of the probe step is superior to
      that obtained in any studies on this molecule to date. We focus on the behavior
      of the 13(1) (C-CH(3) stretch) and 7a(1) (C-F stretch) vibrational states whose
      dynamics have previously received significant attention, but with contradictory
      results. We show conclusively that, under our experimental conditions, the 7a(1)
      vibrational state undergoes significantly more efficient IVR than does the 13(1)
      state. Indeed, under the experimental conditions used here, the 13(1) state
      undergoes very little IVR. These two states are especially interesting because
      their energies are only 36 cm(-1) apart, and the two vibrational modes have the
      same symmetry. We discuss the role of experimental conditions in observations of
      IVR in some detail, and thereby suggest explanations for the discrepancies
      reported to date.

PMID- 17014176
TI  - Electronically excited states of tryptamine and its microhydrated complex.
AB  - The lowest electronically excited singlet states of tryptamine and the tryptamine
      (H2O)1 cluster have been studied, using time dependent density functional theory
      for determination of the geometries and multireference configuration interaction
      for the vertical and adiabatic excitation energies, the permanent dipole moments,
      and the transition dipole moment orientations. All molecular properties of the
      seven experimentally observed conformers of tryptamine could be reproduced with
      high accuracy. A strong solvent reorientation has been found upon electronic
      excitation of the 1:1 water cluster of tryptamine to the L(a) and L(b) states.
      The adiabatically lowest excited singlet state in case of the tryptamine monomer
      is the L(b) state, while for the 1:1 water complex, the L(a) is calculated below
      the L(b) state.

PMID- 17014177
TI  - Quantum control of internal conversion in 24-vibrational-mode pyrazine.
AB  - Quantum control of the S(2)-->S(1) internal conversion in a complete 24-mode
      dimensionality model of pyrazine is demonstrated. The fully quantum mechanical
      study makes use of the recently developed "QP algorithm" for performing accurate
      computations of projected quantum dynamics and the role of overlapping resonances
      in control. The results are extremely encouraging, demonstrating active control
      over internal conversion so as to almost completely suppress the process over
      time scales of approximately 50-100 fs [well in excess of the natural internal
      conversion times (approximately 20 fs)] or to accelerate it to complete internal
      conversion in less than 5 fs. A number of new diagnostics are introduced to
      demonstrate the significance of overlapping-resonance contributions to control.
      Control is far better than for a reduced dimensionality model of pyrazine,
      presumably because of the increased degree of overlap between bound state
      resonances existing in the full dimensionality case.

PMID- 17014178
TI  - The lowest energy states of the group-IIIA-group-VA heteronuclear diatomics: BN,
      BP, AlN, and AlP from full configuration interaction calculations.
AB  - Full configuration interaction (CI) calculations on the group-IIIA-group-VA
      diatomic molecules BN, BP, AlN, and AlP have been performed with the cc-pVTZ
      correlation-consistent basis set and compared to CCSD(T) calculations with the
      same basis set. The CCSD(T) calculations are good to better than 1 kcal/mol in
      comparison with the full CI results if the T(1) diagnostic is small and to within
      about 2 kcal/mol if the T(1) diagnostic is large. Inspection of the T(2)
      amplitudes shows that the simple T(1) diagnostic is providing useful insight into
      the quality of the starting wave function. The ground state of BN, BP, and AlN is
      predicted to be the (3)Pi and, for AlP, the ground state is predicted to be
      (3)Sigma(-). For all molecules except BP, there is an excited state within 1.1
      kcal/mol of the ground state. The ordering of the state energies can be explained
      in terms of simple orbital and bonding models. The results provide little
      evidence for placing the pi orbital below the sigma orbital for the ground state
      of these heteronuclear diatomic molecules.

PMID- 17014179
TI  - Ultrafast processes in OClO molecules excited by femtosecond laser pulses at 386
      409 nm.
AB  - Ultrafast dissociation dynamics in OClO molecules is studied, induced by
      femtosecond laser pulses in the wavelength region from 386 to 409 nm, i.e.,
      within the wide absorption band to the (approximately)A (2)A(2) electronic state.
      The decay of the initially excited state due to nonadiabatic coupling to the
      close lying (2)A(1) and (2)B(2) electronic states proceeds with a time constant
      increasing from 4.6 ps at 386 nm to 30 ps at 408.5 nm. Dissociation of the OClO
      molecule occurs after internal conversion within about 250 fs. In addition, a
      minor channel of direct excitation of the (2)A(1) electronic state has been
      identified, the lifetime of which increases from a few 100 fs at 386 nm to 2.2 ps
      at 408.5 nm. Simultaneous excitation of two neighboring vibrational bands in the
      (approximately)A (2)A(2) state leads to a coherent oscillation of the parent ion
      signal with the frequency difference of both modes.

PMID- 17014181
TI  - Path integral ground state study of finite-size systems: application to small
      (parahydrogen)N (N=2-20) clusters.
AB  - We use the path integral ground state method to study the energetic and
      structural properties of small para-H2 clusters of sizes ranging from 2 to 20
      molecules. A fourth order formula is used to approximate the short imaginary-time
      propagator and two interaction potentials are considered. Our results are
      compared to those of exact basis set calculations and other quantum Monte Carlo
      methods when available. We find that for all cluster sizes considered, our
      results show a lower ground state energy than literature values obtained by
      diffusion Monte Carlo and variational Monte Carlo. For the dimer and trimer,
      ground state energies are in good agreement with exact results obtained using the
      discrete variable representation. Structural properties are found to be
      insensitive to the choice of interaction potential. We explore the use of Pekeris
      coordinates to analyze the importance of linear arrangement in trimers and for
      trimers within clusters of larger size.

PMID- 17014180
TI  - Matching-pursuit/split-operator-Fourier-transform simulations of excited-state
      nonadiabatic quantum dynamics in pyrazine.
AB  - A simple approach for numerically exact simulations of nonadiabatic quantum
      dynamics in multidimensional systems is introduced and applied to the description
      of the photoabsorption spectroscopy of pyrazine. The propagation scheme
      generalizes the recently developed matching-pursuit/split-operator-Fourier
      transform (MP/SOFT) method [Y. Wu and V. S. Batista, J. Chem. Phys. 121, 1676
      (2004)] to simulations of nonadiabatic quantum dynamics. The time-evolution
      operator is applied, as defined by the Trotter expansion to second order
      accuracy, in dynamically adaptive coherent-state expansions. These
      representations are obtained by combining the matching-pursuit algorithm with a
      gradient-based optimization method. The accuracy and efficiency of the resulting
      computational approach are demonstrated in calculations of time-dependent
      survival amplitudes and photoabsorption cross sections, using a model Hamiltonian
      that allows for direct comparisons with benchmark calculations. Simulations in
      full-dimensional potential energy surfaces involve the propagation of a 24
      dimensional wave packet to describe the S(1)S(2) interconversion of pyrazine
      after S(0)-->S(2) photoexcitation. The reported results show that the generalized
      MP/SOFT method is a practical and accurate approach to model nonadiabatic
      reaction dynamics in polyatomic systems.

PMID- 17014182
TI  - Optical control of the singlet-triplet transition in Rb2.
AB  - By controlling nonresonant dynamic Stark shifts it is possible to effectively
      decouple the intramolecular couplings of simple molecules. We have illustrated
      this effect in the 1 (1)Sigma(u)-->1 (3)Pi(u) transition in Rb(2). The laser
      scheme implies two important control knobs: the laser frequency, which must be
      chosen to avoid both single and multiphoton resonances and to select different
      electronic environments for the singlet and triplet states, and the pulse
      intensity, which must amplify the asymmetry in the dynamic polarizabilities that
      allows the decoupling, avoiding undesired strong-pulse effects. The mechanism of
      the scheme implies not only brute-force energy shifts but also light-induced
      reshaping of the potentials to avoid the undesired crossings. Quantitative
      aspects of the method are analyzed by using molecular models of increasing
      complexity for Rb(2).

PMID- 17014183
TI  - Quasiclassical trajectory study of the Cl+CH4 reaction dynamics on a quadratic
      configuration interaction with single and double excitation interpolated
      potential energy surface.
AB  - An ab initio interpolated potential energy surface (PES) for the Cl+CH(4)
      reactive system has been constructed using the interpolation method of Collins
      and co-workers [J. Chem. Phys. 102, 5647 (1995); 108, 8302 (1998); 111, 816
      (1999); Theor. Chem. Acc. 108, 313 (2002)]. The ab initio calculations have been
      performed using quadratic configuration interaction with single and double
      excitation theory to build the PES. A simple scaling all correlation technique
      has been used to obtain a PES which yields a barrier height and reaction energy
      in good agreement with high level ab initio calculations and experimental
      measurements. Using these interpolated PESs, a detailed quasiclassical trajectory
      study of integral and differential cross sections, product rovibrational
      populations, and internal energy distributions has been carried out for the
      Cl+CH(4) and Cl+CD(4) reactions, and the theoretical results have been compared
      with the available experimental data. It has been shown that the calculated total
      reaction cross sections versus collision energy for the Cl+CH(4) and Cl+CD(4)
      reactions is very sensitive to the barrier height. Besides, due to the zero-point
      energy (ZPE) leakage of the CH(4) molecule to the reaction coordinate in the
      quasiclassical trajectory (QCT) calculations, the reaction threshold falls below
      the barrier height of the PES. The ZPE leakage leads to CH(3) and HCl coproducts
      with internal energy below its corresponding ZPEs. We have shown that a Gaussian
      binning (GB) analysis of the trajectories yields excitation functions in somehow
      better agreement with the experimental determinations. The HCl(v'=0) and
      DCl(v'=0) rotational distributions are as well very sensitive to the ZPE problem.
      The GB correction narrows and shifts the rotational distributions to lower values
      of the rotational quantum numbers. However, the present QCT rotational
      distributions are still hotter than the experimental distributions. In both
      reactions the angular distributions shift from backward peaked to sideways peaked
      as collision energy increases, as seen in the experiments and other theoretical
      calculations.

PMID- 17014184
TI  - An ignored but most favorable channel for NCO+C2H2 reaction.
AB  - The NCO+C(2)H(2) reaction has been considered as a prototype for understanding
      the chemical reactivity of the isocyanate radical towards unsaturated
      hydrocarbons in fuel-rich combustion. It has also been proposed to provide an
      effective route for formation of oxazole-containing compounds in organic
      synthesis, and might have potential applications in interstellar processes.
      Unfortunately, this reaction has met mechanistic controversy both between
      experiments and between experiments and theoretical calculations. In this paper,
      detailed theoretical investigations at the Becke's three parameter Lee-Yang-Parr
      B3LYP6-31G(d), B3LYP6-311++G(d,p), quadratic configuration interaction with
      single and double excitations QCISD6-31G(d), and Gaussian-3 levels are performed
      for the NCO+C(2)H(2) reaction, covering various entrance, isomerization, and
      decomposition channels. Also, the highly cost-expensive coupled-cluster theory
      including single and double excitations and perturbative inclusion of triple
      excitations CCSD(T)/aug-cc-pVTZ single-point energy calculation is performed for
      the geometries obtained at the Becke's three parameter Lee-Yang-Parr-B3LYP6
      311++G(d,p) level. A previously ignored yet most favorable channel via a four
      membered ring intermediate with allyl radical character is found. However,
      formation of P(3) H+HCCNCO and the five-membered ring channel predicted by
      previous experimental and theoretical studies is kinetically much less
      competitive. With the new channel, master equation rate constant calculations
      over a wide range of temperatures (298-1500 K) and pressures (10-560 Torr) show
      that the predicted total rate constants exhibit a positive-temperature dependence
      and no distinct pressure dependence effect. This is in qualitative agreement with
      available experimental results. Under the experimental conditions, the predicted
      values are about 50% lower than the latest experimental results. Also, the
      branching ratio variations of the fragments P(2) HCN+HCCO and P(5) OCCHCN+H as
      well as the intermediates L1 HCHCNCO, r4 cCHCHNC-O, and L5 NCHCHCO are discussed
      with respect to the temperature and pressure. Future experimental
      reinvestigations are strongly desired to test the newly predicted channel for the
      model NCO+C(2)H(2) reaction. Implications of the present results in various
      fields are discussed.

PMID- 17014185
TI  - On the nonlinear variation of dc conductivity with dielectric relaxation time.
AB  - The long-known observations that dc conductivity sigma(dc) of an ultraviscous
      liquid varies nonlinearly with the dielectric relaxation time tau, and the slope
      of the log sigma(dc) against log tau plot deviates from -1 are currently seen as
      two of the violations of the Debye-Stokes-Einstein equation. Here we provide a
      formalism using a zeroth order Bjerrum description for ion association to show
      that in addition to its variation with temperature T and pressure P, impurity ion
      population varies with a liquid's equilibrium dielectric permittivity. Inclusion
      of this electrostatic effect modifies the Debye-Stokes-Einstein equation to
      log(sigma(dc)tau)=constant+log alpha, where alpha is the T and P-dependent degree
      of ionic dissociation of an electrolytic impurity. Variation of a liquid's shear
      modulus with T and P would add to the nonlinearity of sigma(dc)-tau relation, as
      would a nonequivalence of the shear and dielectric relaxation times, proton
      transfer along the hydrogen bonds, or occurrence of another chemical process.
      This is illustrated by using the data for ultraviscous acetaminophen-aspirin
      liquid.

PMID- 17014186
TI  - Crystal-melt coexistence under shear: Interpreting the nonlinear rheology.
AB  - We propose a phenomenological model for shear-induced melting aimed at assisting
      the design of experimental studies of this phenomenon. For increasing strain
      rates, the model predicts the changes in liquid fraction and shear stress as a
      function of interfacial supercooling. We discuss the experimental conditions
      under which shear-induced melting could be observed in a range of materials.

PMID- 17014187
TI  - Structural anomalies for a three dimensional isotropic core-softened potential.
AB  - Using molecular dynamics simulations we investigate the structure of a system of
      particles interacting through a continuous core-softened interparticle potential.
      We found for the translational order parameter t a local maximum at a density
      rho(t-max) and a local minimum at rho(t-min)>rho(t-max). Between rho(t-max) and
      rho(t-min), the t parameter anomalously decreases upon increasing pressure. For
      the orientational order parameter Q(6) a maximum was observed at a density rho(t
      max)<rho(Qmax)<rho(t-min). For densities between rho(Qmax) and rho(t-min), both
      the translational (t) and orientational (Q(6)) order parameters have anomalous
      behavior. We know that this system also exhibits density and diffusion anomalies.
      We found that the region in the pressure-temperature phase diagram of the
      structural anomaly englobes the region of the diffusion anomaly that is larger
      than the region limited by the temperature of maximum density. This cascade of
      anomalies (structural, dynamic, and thermodynamic) for our model has the same
      hierarchy as that observed for the simple point charge/extended water.

PMID- 17014188
TI  - Simulation of symmetric tricritical behavior in electrolytes.
AB  - Despite extensive experimental, theoretical, and simulation efforts, a unified
      description of ionic phase transitions and criticality has not yet emerged. In
      this work, we investigate the phase behavior of the restricted primitive model of
      electrolyte solutions on the simple cubic lattice using grand canonical Monte
      Carlo simulations and finite-size scaling techniques. The phase diagram of the
      system is distinctly different from its continuum-space analog. We find order
      disorder transitions for reduced temperatures T* < or approximately 0.51, where
      the ordered structures resemble those of the NaCl crystal. The order-disorder
      transition is continuous for 0.15 < or approximately T* < or approximately 0.51
      and becomes first order at lower temperatures. The line of first-order
      transitions is a line of three-phase coexistence between a disordered and two
      ordered phases. The line of continuous, second-order transitions meets this line
      of triple points at a tricritical point at T* approximately equal to 0.1475. We
      locate the line of continuous transitions, and the line of triple points using
      finite-size scaling techniques. The tricritical temperature is estimated by
      extrapolation of the size-dependent tricritical temperatures obtained from a
      sixth-order Landau expansion of the free energy. Our calculated phase diagram is
      in qualitative agreement with mean-field theories.

PMID- 17014189
TI  - Apparent mismatch between extended x-ray absorption fine structure and
      diffraction structures of crystalline metastable WO3 phases.
AB  - The local structure of monoclinic, monohydrate, hexagonal, and pyrochlore WO3
      phases was investigated by the extended x-ray absorption fine structure
      spectroscopy as preliminary studies of model compounds of amorphous and thin film
      WO3 based electrochromic species. In the four cases, we found a large W-O
      distribution of distances ranging from 1.70 to 2.35 A. The apparent discrepancy
      of these results and previously published crystal structures are discussed and
      interpreted as the detection of vacancies and local distortion disorder.

PMID- 17014190
TI  - Proton line narrowing in solid-state nuclear magnetic resonance: new insights
      from windowed phase-modulated Lee-Goldburg sequence.
AB  - We present here a bimodal Floquet analysis of the windowed phase-modulated Lee
      Goldburg (wPMLG) sequence for homonuclear dipolar decoupling. One of the main
      criteria for an efficient homonuclear dipolar decoupling scheme is an effective z
      rotation condition. This is brought about by the presence of radio-frequency
      imperfections in the pulse sequence together with a systematic manipulation of
      the wPMLG pulses. Additional improvement in the (1)H spectral resolution was
      obtained by a proper understanding of the off-resonance dependence of the wPMLG
      irradiation scheme based on bimodal Floquet theory. Numerical investigations
      further corroborate both theoretical and experimental findings. Theoretical
      analysis points to accidental degeneracies between the cycle time of the wPMLG
      sequence and the rotor period leading to the experimentally observed off
      resonance dependence of the resolution. Two-dimensional (1)H-(1)H homonuclear
      single-quantum correlation spectra of model amino acids are also presented,
      highlighting the improved spectral resolution of wPMLG sequences.

PMID- 17014191
TI  - Multipole moments and polarizabilities of nonpolar diatomic molecules through
      quantum solvation in solid parahydrogen: the quadrupole moment of N2.
AB  - It is shown in this paper that from the study of the induced infrared absorption
      spectra of homonuclear diatomic molecules solvated as impurities in a molecular
      quantum solid, it is possible to extract information about the rovibrational
      matrix elements of the multipole moments and polarizability of the embedded
      molecule. Theoretical expressions are derived for the integrated absorption
      coefficients of various multipole-field-induced double transitions involving
      guest-host pairs in a solid para-H(2) matrix. The intensities of some of the
      quadrupole moment induced transitions involving the N(2)-para-H(2) pair have been
      measured. From a comparison of the experimental and theoretical intensities,
      rovibrational matrix elements of the quadrupole moment of N(2) are determined in
      its ground vibrational state.

PMID- 17014192
TI  - Thermodynamic scaling of the viscosity of van der Waals, H-bonded, and ionic
      liquids.
AB  - Viscosities eta and their temperature T and volume V dependences are reported for
      seven molecular liquids and polymers. In combination with literature viscosity
      data for five other liquids, we show that the superpositioning of relaxation
      times for various glass-forming materials when expressed as a function of
      TV(gamma), where the exponent gamma is a material constant, can be extended to
      the viscosity. The latter is usually measured to higher temperatures than the
      corresponding relaxation times, demonstrating the validity of the thermodynamic
      scaling throughout the supercooled and higher T regimes. The value of gamma for a
      given liquid principally reflects the magnitude of the intermolecular forces
      (e.g., steepness of the repulsive potential); thus, we find decreasing gamma in
      going from van der Waals fluids to ionic liquids. For some strongly H-bonded
      materials, such as low molecular weight polypropylene glycol and water, the
      superpositioning fails, due to the nontrivial change of chemical structure
      (degree of H bonding) with thermodynamic conditions.

PMID- 17014193
TI  - Homogeneity and Markovity of electronic dephasing in liquid solutions.
AB  - The electronic dephasing dynamics of a solvated chromophore is formulated in
      terms of a non-Markovian master equation. Within this formulation, one describes
      the effect of the nuclear degrees of freedom on the electronic degrees of freedom
      in terms of a memory kernel function, which is explicitly dependent on the
      initial solvent configuration. In the case of homogeneous dynamics, this memory
      kernel becomes independent of the initial configuration. The Markovity of the
      dephasing process is also the most conveniently explored by comparing the results
      obtained via the non-Markovian master equation to these obtained via its
      Markovian counterpart. The homogeneous memory kernel is calculated for a two
      state chromophore in liquid solution, and used to explore the sensitivity of
      photon echo signals to the heterogeneity and non-Markovity of the underlying
      solvation dynamics.

PMID- 17014194
TI  - Effect of finite trajectory length on the correlation function analysis of single
      molecule data.
AB  - The effect of finite trajectory length on single molecule rotational correlation
      functions has been studied by utilizing time series analysis and numerical
      simulations. Correlation functions obtained from the trajectories of length less
      than 100 times the correlation time constant (tau([script-l])) exhibit
      significant deviations from the true correlation function. The distributions of
      sample time constants (tau(F)) and stretching exponents (Beta(F)) are mapped by
      fitting a large number of rotational trajectories to stretched exponentials. As
      the trajectory length gets smaller, the distributions become broader and
      asymmetric and their mean values deviate from the true value predicted by pure
      rotational diffusion. Analysis based on higher order spherical harmonics is
      suggested as a method for minimizing the effect of the trajectory length. The
      distributions of time constants for different higher order spherical harmonics
      are also compared. While the focus of the paper is on rotational correlation
      functions, the general conclusions apply to any dynamical process that yields an
      exponentially decaying correlation function.

PMID- 17014195
TI  - Electron-stimulated production of molecular oxygen in amorphous solid water on
      Pt111: precursor transport through the hydrogen bonding network.
AB  - The low-energy, electron-stimulated production of molecular oxygen from thin
      amorphous solid water (ASW) films adsorbed on Pt(111) is investigated. For ASW
      coverages less than approximately 60 ML, the O(2) electron-stimulated desorption
      (ESD) yield depends on coverage in a manner that is very similar to the H(2) ESD
      yield. In particular, both the O(2) and H(2) ESD yields have a pronounced maximum
      at approximately 20 ML due to reactions at the Pt/water interface. The O(2) yield
      is dose dependent and several precursors (OH, H(2)O(2), and HO(2)) are involved
      in the O(2) production. Layered films of H(2) (16)O and H(2) (18)O are used to
      profile the spatial distribution of the electron-stimulated reactions leading to
      oxygen within the water films. Independent of the ASW film thickness, the final
      reactions leading to O(2) occur at or near the ASW/vacuum interface. However, for
      ASW coverages less than approximately 40 ML, the results indicate that
      dissociation of water molecules at the ASW/Pt interface contributes to the O(2)
      production at the ASW/vacuum interface presumably via the generation of OH
      radicals near the Pt substrate. The OH (or possibly OH(-)) segregates to the
      vacuum interface where it contributes to the reactions at that interface. The
      electron-stimulated migration of precursors to the vacuum interface occurs via
      transport through the hydrogen bond network of the ASW without motion of the
      oxygen atoms. A simple kinetic model of the nonthermal reactions leading to O(2),
      which was previously used to account for reactions in thick ASW films, is
      modified to account for the electron-stimulated migration of precursors.

PMID- 17014196
TI  - First-principles study of interaction of cluster Au32 with CO, H2, and O2.
AB  - First-principles calculations are performed to study the interaction of cluster
      Au(32) with small molecules, such as CO, H(2), and O(2). The cagelike
      Au(32)(I(h)) shows a higher chemical inertness than the amorphous Au(32)(C(1))
      with respect to the interaction with small molecules CO, H(2), and O(2). H(2) can
      only be physically adsorbed on Au(32)(I(h)), while it can be dissociatively
      chemisorbed on Au(32)(C(1)). Although CO can be chemically adsorbed on
      Au(32)(I(h)) and Au(32)(C(1)) with one electron transferred from Au(32) to the
      antibonding pi* orbit of CO, it is bound more strongly on Au(32)(C(1)) than on
      Au(32)(I(h)). Spin polarized and spin nonpolarized calculations result almost
      identical ground state structures of Au(32)(I(h))-O(2) and Au(32)(C(1))-O(2), in
      which O(2) is dissociatively chemisorbed.

PMID- 17014197
TI  - Surface enhanced Raman optical activity of molecules on orientationally averaged
      substrates: theory of electromagnetic effects.
AB  - We present a model for electromagnetic enhancements in surface enhanced Raman
      optical activity (SEROA) spectroscopy. The model extends previous treatments of
      SEROA to substrates, such as metal nanoparticles in solution, that are
      orientationally averaged with respect to the laboratory frame. Our theoretical
      treatment combines analytical expressions for unenhanced Raman optical activity
      with molecular polarizability tensors that are dressed by the substrate's
      electromagnetic enhancements. We evaluate enhancements from model substrates to
      determine preliminary scaling laws and selection rules for SEROA. We find that
      dipolar substrates enhance Raman optical activity (ROA) scattering less than
      Raman scattering. Evanescent gradient contributions to orientationally averaged
      ROA scale to first or higher orders in the gradient of the incident plane-wave
      field. These evanescent gradient contributions may be large for substrates with
      quadrupolar responses to the plane-wave field gradient. Some substrates may also
      show a ROA contribution that depends only on the molecular electric dipole
      electric dipole polarizability. These conclusions are illustrated via numerical
      calculations of surface enhanced Raman and ROA spectra from (R)-(-)
      bromochlorofluoromethane on various model substrates.

PMID- 17014198
TI  - Density functional theory of homopolymer mixtures confined in a slit.
AB  - A density functional theory (DFT) is developed for polymer mixtures with shorted
      ranged attractive interparticle interactions confined in a slit. Different
      weighting functions are used separately for the repulsive part and the attractive
      part of the excess free energy functional by applying the weighted density
      approximation. The predicted results by DFT are in good agreement with the
      corresponding simulation data indicating the reliability of the theory.
      Furthermore, the center-of-mass profiles and the end-to-end distance
      distributions are obtained by the single chain simulation; the predictions also
      agree well with simulation data. The results reveal that both the attraction of
      the slit wall and the temperature has stronger effect on longer chains than on
      shorter ones because the intrasegment correlation of chains increases with
      increasing chain length.

PMID- 17014199
TI  - Menger sponge-like fractal body created by a novel template method.
AB  - We have established experimental strategies on how to create a Menger sponge-like
      fractal body and how to control its fractal dimension. The essence was to utilize
      alkylketene dimer (AKD), which spontaneously forms super-water-repellent fractal
      surface. We prepared "fractal AKD particles" with fractal surface structure as
      templates of pores in fractal body. The fractal body was synthesized by filling
      the remained space between the packed template particles with a tetramethyl
      orthosilicate solution, solidifying it by the sol-gel process, and removing the
      template by calcinations. We have succeeded in systematically creating fractal
      bodies of silica with different cross-sectional fractal dimensions D(cs)=1.87,
      1.84, and 1.80 using "fractal template particles" compressed under the ratio=1.0,
      2.0, and 3.0, respectively. We also discussed the possibilities of their fractal
      geometries in comparison with mathematical models. We concluded that the created
      fractal bodies were close to a Menger sponge and its modified one. Our
      experimental strategy allows us to design fractality of porous materials.

PMID- 17014200
TI  - The effects of Au aggregate morphology on surface-enhanced Raman scattering
      enhancement.
AB  - We have identified empirically a relationship between the surface morphology of
      small individual aggregates (<100 Au nanoparticles) and surface-enhanced Raman
      scattering (SERS) enhancement. We have found that multilayer aggregates generated
      greater SERS enhancement than aggregates limited to two-dimensional (2D) or one
      dimensional structures, independent of the number of particles. SERS intensity
      was measured using the 730 cm(-1) vibrational mode of the adsorbed adenine
      molecule on 75 nm Au particles, at an excitation wavelength of 632.8 nm. To gain
      insight into these relationships and its mechanism, we developed a qualitative
      model that considers the collections of interacting Au nanoparticles of an
      individual aggregate as a continuous single entity that retains its salient
      features. We found the dimensions of the modeled surface features to be
      comparable with those found in rough metal surfaces, known to sustain surface
      plasmon resonance and generate strong SERS enhancement. Among the aggregates that
      we have characterized, a three 75 nm nanoparticle system was the smallest to
      generate strong SERS enhancement. However, we also identified single individual
      Au nanoparticles as SERS active at the same wavelength, but with a diameter twice
      in size. For example, we observed a symmetric SERS-active particle of 180 nm in
      diameter. Such individual nanoparticles generated SERS enhancement on the same
      order of magnitude as the small monolayer Au aggregates, an intensity value
      significantly stronger than predicted in recent theoretical studies. We also
      found that an aspect of our model that relates the dimensions of its features to
      SERS enhancement is also applicable to single individual Au particles. We
      conclude that the size of the nanoparticle itself, or the size of a protrusion of
      an irregularly shaped single Au particle, will contribute to SERS enhancement
      provided that its dimensions satisfy the conditions for plasmon resonance. In
      addition, by considering the ratio of the generated intensities of typical 2D Au
      aggregates to the enhancement of individual SERS-active particles, a value of
      approximately 2 is determined. Its moderate value suggests that it is not the
      aggregation effect that is responsible for much of the observed SERS enhancement
      but the surface region associated with the SERS-active site.

PMID- 17014201
TI  - Plasmon hybridization in nanoshells with a nonconcentric core.
AB  - We apply the plasmon hybridization method to a nanoshell with a nonconcentric
      (offset) core and investigate how the energy and excitation cross section of the
      plasmon modes depend on the offset distance D of the inner core from the
      nanoshell center. A two-center spherical coordinate system is used for
      mathematical convenience. It is shown that the presence of an offset core shifts
      the plasmon energies and makes higher multipolar nanoshell plasmons dipole active
      and visible in the optical spectrum. The dependence of the plasmon shifts on D is
      weak for small offsets but strong for large offsets. The polarization dependence
      of the optical absorption spectra is found to be relatively weak. The
      electromagnetic field enhancements are shown to be much larger than on a
      concentric nanoshell. The results agree very well with results from finite
      difference time domain simulations.

PMID- 17014202
TI  - Langevin dynamics simulations of polymer translocation through nanopores.
AB  - We investigate the dynamics of polymer translocation through a nanopore using two
      dimensional Langevin dynamics simulations. In the absence of an external driving
      force, we consider a polymer which is initially placed in the middle of the pore
      and study the escape time tau(e) required for the polymer to completely exit the
      pore on either side. The distribution of the escape times is wide and has a long
      tail. We find that tau(e) scales with the chain length N as tau(e) approximately
      N(1+2nu), where nu is the Flory exponent. For driven translocation, we
      concentrate on the influence of the friction coefficient xi, the driving force E,
      and the length of the chain N on the translocation time tau, which is defined as
      the time duration between the first monomer entering the pore and the last
      monomer leaving the pore. For strong driving forces, the distribution of
      translocation times is symmetric and narrow without a long tail and tau
      approximately E(-1). The influence of xi depends on the ratio between the driving
      and frictional forces. For intermediate xi, we find a crossover scaling for tau
      with N from tau approximately N(2nu) for relatively short chains to tau
      approximately N(1+nu) for longer chains. However, for higher xi, only tau
      approximately N(1+nu) is observed even for short chains, and there is no
      crossover behavior. This result can be explained by the fact that increasing xi
      increases the Rouse relaxation time of the chain, in which case even relatively
      short chains have no time to relax during translocation. Our results are in good
      agreement with previous simulations based on the fluctuating bond lattice model
      of polymers at intermediate friction values, but reveal additional features of
      dependency on friction.

PMID- 17014203
TI  - Atomistic simulation of structure and dynamics of columnar phases of
      hexabenzocoronene derivatives.
AB  - Using atomistic molecular dynamics simulations we study solid and liquid
      crystalline columnar discotic phases formed by alkyl-substituted
      hexabenzocoronene mesogens. Correlations between the molecular structure,
      packing, and dynamical properties of these materials are established.

PMID- 17014204
TI  - The Soret effect in dilute polymer solutions: influence of chain length, chain
      stiffness, and solvent quality.
AB  - Thermal diffusion in dilute polymer solutions is studied by reverse
      nonequilibrium molecular dynamics. The polymers are represented by a generic bead
      spring model. The influence of the solvent quality on the Soret coefficient is
      investigated. At constant temperature and monomer fraction, a better solvent
      quality causes a higher affinity for the polymer to the cold region. This may
      even go to thermal-diffusion-induced phase separation. The sign of the Soret
      coefficient changes in a symmetric nonideal binary Lennard-Jones solution when
      the solvent quality switches from good to poor. The known independence of the
      thermal diffusion coefficients of the molecular weight is reproduced for three
      groups of polymers with different chain stiffnesses. The thermal diffusion
      coefficients reach constant values at chain lengths of around two to three times
      the persistence length. Moreover, rigid polymers have higher Soret coefficients
      and thermal diffusion coefficients than more flexible polymers.

PMID- 17014205
TI  - Effect of surface elasticity on the motion of a droplet in a viscous fluid.
AB  - The motion of a droplet with adsorption layer in a viscous incompressible fluid
      is studied on the basis of the linearized Navier-Stokes equations. It is shown
      that dilatational elasticity of the layer has a strong effect on the decay of
      velocity after a sudden impulse. If the elasticity is sufficiently strong the
      droplet shows backtracking, i.e., during part of the time the velocity relaxation
      function becomes negative. The motion is independent of the surface shear modulus
      or surface shear viscosity. The friction coefficient of the droplet at zero
      frequency is the same as for a rigid sphere with stick boundary conditions,
      independent of the elasticity modulus.

PMID- 17014206
TI  - Chaotic dynamics in a class of three dimensional glass networks.
AB  - In this paper, we study chaotic dynamics of a class of three-dimensional Glass
      networks with different decay constants, illustrate how the horseshoe is
      generated, and present a rigorous computer-assisted verification of chaoticity by
      virtue of interval analysis and topological horseshoe theory.

PMID- 17014207
TI  - A method for vibrational assessment of cortical bone.
AB  - Large bones from many anatomical locations of the human skeleton consist of an
      outer shaft (cortex) surrounding a highly porous internal region (trabecular
      bone) whose structure is reminiscent of a disordered cubic network. Age related
      degradation of cortical and trabecular bone takes different forms. Trabecular
      bone weakens primarily by loss of connectivity of the porous network, and recent
      studies have shown that vibrational response can be used to obtain reliable
      estimates for loss of its strength. In contrast, cortical bone degrades via the
      accumulation of long fractures and changes in the level of mineralization of the
      bone tissue. In this paper, we model cortical bone by an initially solid specimen
      with uniform density to which long fractures are introduced; we find that, as in
      the case of trabecular bone, vibrational assessment provides more reliable
      estimates of residual strength in cortical bone than is possible using
      measurements of density or porosity.

PMID- 17014208
TI  - Direct observation of a "devil's staircase" in wave-particle interaction.
AB  - We report the experimental observation of a "devil's staircase" in a time
      dependent system considered as a paradigm for the transition to large-scale chaos
      in the universality class of Hamiltonian systems. A test electron beam is used to
      observe its non-self-consistent interaction with externally excited wave(s) in a
      traveling wave tube (TWT). A trochoidal energy analyzer records the beam energy
      distribution at the output of the interaction line. An arbitrary waveform
      generator is used to launch a prescribed spectrum of waves along the slow wave
      structure (a 4 m long helix) of the TWT. The resonant velocity domain associated
      to a single wave is observed, as well as the transition to large-scale chaos when
      the resonant domains of two waves and their secondary resonances overlap. This
      transition exhibits a "devil's staircase" behavior for increasing excitation
      amplitude, due to the nonlinear forcing by the second wave on the pendulum-like
      motion of a charged particle in one electrostatic wave.

PMID- 17014209
TI  - Switch control for piecewise affine chaotic systems.
AB  - Switch control can be imposed naturally on the piecewise affine system, where the
      control action switches from an affine subsystem to another according to switch
      conditions depending on the system states. In this paper we present such
      piecewise feedback control for stabilizing unstable equilibrium points of
      piecewise affine systems. The noise effect on the stabilization is also
      investigated. The original Chua's circuit is used to illustrate our results.

PMID- 17014210
TI  - Degeneracy of time series models: the best model is not always the correct model.
AB  - There are a number of good techniques for finding, in some sense, the best model
      of a deterministic system given a time series of observations. We examine a
      problem called model degeneracy, which has the consequence that even when a
      perfect model of a system exists, one does not find it using the best techniques
      currently available. The problem is illustrated using global polynomial models
      and the theory of Grobner bases.

PMID- 17014211
TI  - Standing solutions of one-dimensional Boiti-Leon-Pempinelli-Spire system
      localized in space and periodical in time.
AB  - By means of a special variable separation approach, a common formula with two
      arbitrary functions has been obtained for suitable physical quantity of (1+1)
      dimensional model such as Boiti-Leon-Pempinelli-Spire system. Based on the
      derived formula, some significant types of solitons such as compacton, peakon,
      and loop solutions localized in space and periodical in time are simultaneously
      constructed from the (1+1)-dimensional soliton system by entrancing appropriate
      piecewise smooth functions and multivalued functions.

PMID- 17014212
TI  - Comparison of the Newtonian and relativistic predicted trajectories for a low
      speed periodically delta-kicked system.
AB  - The dynamics of a periodically delta-kicked Hamiltonian system moving at low
      speed (i.e., at speed much less than the speed of light) is studied numerically.
      In particular, the trajectory of the system predicted by Newtonian mechanics is
      compared with the trajectory predicted by special relativistic mechanics for the
      same parameters and initial conditions. We find that the Newtonian trajectory,
      although close to the relativistic trajectory for some time, eventually disagrees
      completely with the relativistic trajectory, regardless of the nature (chaotic,
      nonchaotic) of each trajectory. However, the agreement breaks down very fast if
      either the Newtonian or relativistic trajectory is chaotic, but very much slower
      if both the Newtonian and relativistic trajectories are nonchaotic. In the former
      chaotic case, the difference between the Newtonian and relativistic values for
      both position and momentum grows, on average, exponentially. In the latter
      nonchaotic case, the difference grows much slower, for example, linearly on
      average.

PMID- 17014213
TI  - Fractional statistical mechanics.
AB  - The Liouville and first Bogoliubov hierarchy equations with derivatives of
      noninteger order are derived. The fractional Liouville equation is obtained from
      the conservation of probability to find a system in a fractional volume element.
      This equation is used to obtain Bogoliubov hierarchy and fractional kinetic
      equations with fractional derivatives. Statistical mechanics of fractional
      generalization of the Hamiltonian systems is discussed. Liouville and Bogoliubov
      equations with fractional coordinate and momenta derivatives are considered as a
      basis to derive fractional kinetic equations. The Fokker-Planck-Zaslavsky
      equation that has fractional phase-space derivatives is obtained from the
      fractional Bogoliubov equation. The linear fractional kinetic equation for
      distribution of the charged particles is considered.

PMID- 17014214
TI  - Tracking unstable steady states and periodic orbits of oscillatory and chaotic
      electrochemical systems using delayed feedback control.
AB  - Experimental results are presented on successful application of delayed-feedback
      control algorithms for tracking unstable steady states and periodic orbits of
      electrochemical dissolution systems. Time-delay autosynchronization and delay
      optimization with a descent gradient method were applied for stationary states
      and periodic orbits, respectively. These tracking algorithms are utilized in
      constructing experimental bifurcation diagrams of the studied electrochemical
      systems in which Hopf, saddle-node, saddle-loop, and period-doubling bifurcations
      take place.

PMID- 17014215
TI  - Kinematic description of wave propagation through a chemical diode.
AB  - The geometry of an active medium can cause wave blocking and induce
      unidirectional propagation. This well established phenomenon was studied in a
      previous paper within the framework of the photosensitive Belousov-Zhabotinsky
      reaction and the associated Oregonator model. In the present paper, as an
      extension of that study, the main factors that influence this phenomenon are
      interpreted in terms of a kinematic model.

PMID- 17014216
TI  - Conservative spatial chaos of buckled elastic linkages.
AB  - Buckling of an elastic linkage under general loading is investigated. We show
      that buckling is related to an initial value problem, which is always a
      conservative, area-preserving mapping, even if the original static problem is
      nonconservative. In some special cases, we construct the global bifurcation
      diagrams, and argue that their complicated structure is a consequence of spatial
      chaos. We characterize spatial chaos by the associated initial value problem's
      topological entropy, which turns out to be related to the number of buckled
      configurations.

PMID- 17014217
TI  - Relations between distributional and Devaney chaos.
AB  - Recently, it was proven that chaos in the sense of Devaney and weak mixing both
      imply chaos in the sense of Li and Yorke. In this article we give explicit
      examples that any of these two implications do not hold for distributional chaos.

PMID- 17014218
TI  - A note on chaotic unimodal maps and applications.
AB  - Based on the word-lift technique of symbolic dynamics of one-dimensional unimodal
      maps, we investigate the relation between chaotic kneading sequences and linear
      maximum-length shift-register sequences. Theoretical and numerical evidence that
      the set of the maximum-length shift-register sequences is a subset of the set of
      the universal sequence of one-dimensional chaotic unimodal maps is given. By
      stabilizing unstable periodic orbits on superstable periodic orbits, we also
      develop techniques to control the generation of long binary sequences.

PMID- 17014219
TI  - Complex dynamics in simple Hopfield neural networks.
AB  - A class of simple Hopfield neural networks with a parameter is investigated.
      Numerical simulations show that the simple Hopfield neural networks can display
      chaotic attractors and limit cycles for different parameters. The Lyapunov
      exponents are calculated; the bifurcation plot and several important phase
      portraits are presented as well. By virtue of a recent result of horseshoe theory
      in dynamical systems, we present rigorous computer-assisted verifications for
      chaotic behavior in the simple Hopfield neural networks for certain parameters
      and give a brief discussion on the robustness of the chaotic behavior.
      Quantitative descriptions of the complexity of these neural networks are also
      given in terms of topological entropy.

PMID- 17014220
TI  - Initiation of re-entry in an excitable medium: structural investigation of
      cardiac tissue using a genetic algorithm.
AB  - The detailed mechanisms by which re-entry and ventricular fibrillation are
      initiated in the heart remain poorly understood because they are difficult to
      investigate experimentally. We have used a simplified excitable media
      computational model of action potential propagation to systematically study how
      re-entry can be produced by diffuse regions of inexcitable tissue. Patterns of
      excitable and inexcitable tissue were generated using a genetic algorithm. The
      inexcitable tissue was modeled in two ways: (i) diffusive, electrically connected
      but inexcitable tissue, or (ii) zero-flux, areas of tissue electrically
      disconnected in the same way as zero-flux boundary conditions. We were able to
      evolve patterns of diffuse inexcitable tissue that favored re-entry, but no
      single structure or pattern emerged. Diffusive inexcitable regions were
      inherently less arrhythmogenic than zero-flux inexcitable ones.

PMID- 17014221
TI  - Periodic solution and chaotic strange attractor for shunting inhibitory cellular
      neural networks with impulses.
AB  - By using the continuation theorem of coincidence degree theory and constructing
      suitable Lyapunov functions, we study the existence, uniqueness, and global
      exponential stability of periodic solution for shunting inhibitory cellular
      neural networks with impulses, dx(ij)dt=-a(ij)x(ij)- summation
      operator(C(kl)inN(r)(i,j))C(ij) (kl)f(ij)[x(kl)(t)]x(ij)+L(ij)(t), t>0,t not
      equal t(k); Deltax(ij)(t(k))=x(ij)(t(k) (+))-x(ij)(t(k) (-))=I(k)[x(ij)(t(k))],
      k=1,2,...] . Furthermore, the numerical simulation shows that our system can
      occur in many forms of complexities, including periodic oscillation and chaotic
      strange attractor. To the best of our knowledge, these results have been obtained
      for the first time. Some researchers have introduced impulses into their models,
      but analogous results have never been found.

PMID- 17014222
TI  - Chaotic mixing and transport in a meandering jet flow.
AB  - Mixing and transport of passive particles are studied in a simple kinematic model
      of a meandering jet flow motivated by the problem of lateral mixing and transport
      in the Gulf Stream. We briefly discuss a model stream function, Hamiltonian
      advection equations, stationary points, and bifurcations. The phase portrait of
      the chosen model flow in the moving reference frame consists of a central
      eastward jet, chains of northern and southern circulations, and peripheral
      westward currents. Under a periodic perturbation of the meander's amplitude, the
      topology of the phase space is complicated by the presence of chaotic layers and
      chains of oscillatory and ballistic islands with sticky boundaries immersed into
      a stochastic sea. Typical chaotic trajectories of advected particles are shown to
      demonstrate a complicated behavior with long flights in both the directions of
      motion intermittent with trapping in the circulation cells being stuck to the
      boundaries of vortex cores and resonant islands. Transport is asymmetric in the
      sense that mixing between the circulations and the peripheral currents is, in
      general, different from mixing between the circulations and the jet. The
      transport properties are characterized by probability distribution functions
      (PDFs) of durations and lengths of flights. Both the PDFs exhibit at their tails
      power-law decay with different values of exponents.

PMID- 17014223
TI  - Encryption and decryption of images with chaotic map lattices.
AB  - We propose a secure algorithm for direct encryption and decryption of digital
      images with chaotic map lattices. The basic idea is to convert, pixel by pixel,
      the image color to chaotic logistic maps one-way coupled by initial conditions.
      After small numbers of iterations and cycles, the image becomes indistinguishable
      due to inherent properties of chaotic systems. Since the maps are coupled, the
      image can be completely recovered by the decryption algorithm if map parameters,
      number of iterations, number of cycles, and the image size are exactly known.

PMID- 17014224
TI  - Ultra-high-frequency chaos in a time-delay electronic device with band-limited
      feedback.
AB  - We report an experimental study of ultra-high-frequency chaotic dynamics
      generated in a delay-dynamical electronic device. It consists of a transistor
      based nonlinearity, commercially-available amplifiers, and a transmission-line
      for feedback. The feedback is band-limited, allowing tuning of the characteristic
      time-scales of both the periodic and high-dimensional chaotic oscillations that
      can be generated with the device. As an example, periodic oscillations ranging
      from 48 to 913 MHz are demonstrated. We develop a model and use it to compare the
      experimentally observed Hopf bifurcation of the steady-state to existing theory
      [Illing and Gauthier, Physica D 210, 180 (2005)]. We find good quantitative
      agreement of the predicted and the measured bifurcation threshold, bifurcation
      type and oscillation frequency. Numerical integration of the model yields
      quasiperiodic and high dimensional chaotic solutions (Lyapunov dimension
      approximately 13), which match qualitatively the observed device dynamics.

PMID- 17014225
TI  - Breakup of shearless meanders and "outer" tori in the standard nontwist map.
AB  - The breakup of shearless invariant tori with winding number
      omega=(11+gamma)(12+gamma) (in continued fraction representation) of the standard
      nontwist map is studied numerically using Greene's residue criterion. Tori of
      this winding number can assume the shape of meanders [folded-over invariant tori
      which are not graphs over the x axis in (x,y) phase space], whose breakup is the
      first point of focus here. Secondly, multiple shearless orbits of this winding
      number can exist, leading to a new type of breakup scenario. Results are
      discussed within the framework of the renormalization group for area-preserving
      maps. Regularity of the critical tori is also investigated.

PMID- 17014226
TI  - Tracking control and synchronization of four-dimensional hyperchaotic Rossler
      system.
AB  - In this paper we study the problem of the four-dimensional hyperchaotic Rossler
      system tracking control. A controller based on the reference signal is designed.
      It is theoretically proved that the controller can make the error converge to
      zero exponentially. Numerical results have verified the validity of the
      controller. The Rossler system cannot only track any reference signal fast, but
      can synchronize with identical or different chaotic systems.

PMID- 17014227
TI  - Experimental study of the transitions between synchronous chaos and a periodic
      rotating wave.
AB  - In this work we characterize experimentally the transition between periodic
      rotating waves and synchronized chaos in a ring of unidirectionally coupled
      Lorenz oscillators by means of electronic circuits. The study is complemented by
      numerical and theoretical analysis, and the intermediate states and their
      transitions are identified. The route linking periodic behavior with synchronous
      chaos involves quasiperiodic behavior and a type of high-dimensional chaos known
      as chaotic rotating wave. The high-dimensional chaotic behavior is characterized,
      and is shown to be composed actually by three different behaviors. The
      experimental study confirms the robustness of this route.

PMID- 17014228
TI  - On estimates of Lyapunov exponents of synchronized coupled systems.
AB  - Lyapunov exponents of a synchronized coupled system consist of those of the
      underlying individual systems and the transverse systems, based on a mode
      decomposition along the synchronization manifold. Estimates of bounds on the
      Lyapunov exponents (including transverse Lyapunov exponents) are derived. Several
      examples are used to validate the theoretical estimates.

PMID- 17014229
TI  - Symbolic synchronization and the detection of global properties of coupled
      dynamics from local information.
AB  - We study coupled dynamics on networks using symbolic dynamics. The symbolic
      dynamics is defined by dividing the state space into a small number of regions
      (typically 2), and considering the relative frequencies of the transitions
      between those regions. It turns out that the global qualitative properties of the
      coupled dynamics can be classified into three different phases based on the
      synchronization of the variables and the homogeneity of the symbolic dynamics. Of
      particular interest is the homogeneous unsynchronized phase, where the coupled
      dynamics is in a chaotic unsynchronized state, but exhibits qualitative similar
      symbolic dynamics at all the nodes in the network. We refer to this dynamical
      behavior as symbolic synchronization. In this phase, the local symbolic dynamics
      of any arbitrarily selected node reflects global properties of the coupled
      dynamics, such as qualitative behavior of the largest Lyapunov exponent and phase
      synchronization. This phase depends mainly on the network architecture, and only
      to a smaller extent on the local chaotic dynamical function. We present results
      for two model dynamics, iterations of the one-dimensional logistic map and the
      two-dimensional Henon map, as local dynamical function.

PMID- 17014230
TI  - Generalized projective synchronization of chaotic systems with unknown dead-zone
      input: observer-based approach.
AB  - In this paper we investigate the synchronization problem of drive-response
      chaotic systems with a scalar coupling signal. By using the scalar transmitted
      signal from the drive chaotic system, an observer-based response chaotic system
      with dead-zone nonlinear input is designed. An output feedback control technique
      is derived to achieve generalized projective synchronization between the drive
      system and the response system. Furthermore, an adaptive control law is
      established that guarantees generalized projective synchronization without the
      knowledge of system nonlinearity, and/or system parameters as well as that of
      parameters in dead-zone input nonlinearity. Two illustrative examples are given
      to demonstrate the effectiveness of the proposed synchronization scheme.

PMID- 17014231
TI  - A general multiscroll Lorenz system family and its realization via digital signal
      processors.
AB  - This paper proposes a general multiscroll Lorenz system family by introducing a
      novel parameterized nth-order polynomial transformation. Some basic dynamical
      behaviors of this general multiscroll Lorenz system family are then investigated,
      including bifurcations, maximum Lyapunov exponents, and parameters regions.
      Furthermore, the general multiscroll Lorenz attractors are physically verified by
      using digital signal processors.

PMID- 17014232
TI  - Strange nonchaotic attractors in Harper maps.
AB  - We study the existence of strange nonchaotic attractors (SNA) in the family of
      Harper maps. We prove that for a set of parameters of positive measure, the map
      possesses a SNA. However, the set is nowhere dense. By changing the parameter
      arbitrarily small amounts, the attractor is a smooth curve and not a SNA.

PMID- 17014233
TI  - Mean value and fluctuations in a model of diffusion in porous media.
AB  - We consider a stochastic model for the diffusion in a porous media. For a case
      where the average satisfies an anomalous diffusion equation, we investigate the
      behavior of the realizations around the mean value. The most relevant result of
      our work is that, although the concentration corresponding to each realization
      diffuses normally for large times, it experiences large deviations from the mean
      value during intermediate times. As a consequence, the experimental measurements
      will always depart from the average value of the realizations (with respect to
      the stochastic process) for unpredictable times.

PMID- 17014234
TI  - Self-organized critical gating of ion channels: on the origin of long-term memory
      in dwell time series.
AB  - We present the model of an ion channel, operating in a regime of self-organized
      criticality. It is suggested that complex cooperative dynamics takes place in the
      protein and the overall tension of it facilitates an open or closed state of the
      rigid gates in the pore-making domain. For the first time multifractal spectra of
      ion channel dynamics are presented. Our model well reproduces the multifractal
      properties of ion channel dwell time series and provides an insight on the origin
      of the long-term correlations in these series.

PMID- 17014235
TI  - Introduction: Self-organization in nonequilibrium chemical systems.
AB  - The field of self-organization in nonequilibrium chemical systems comprises the
      study of dynamical phenomena in chemically reacting systems far from equilibrium.
      Systematic exploration of this area began with investigations of the temporal
      behavior of the Belousov-Zhabotinsky oscillating reaction, discovered
      accidentally in the former Soviet Union in the 1950s. The field soon advanced
      into chemical waves in excitable media and propagating fronts. With the
      systematic design of oscillating reactions in the 1980s and the discovery of
      Turing patterns in the 1990s, the scope of these studies expanded dramatically.
      The articles in this Focus Issue provide an overview of the development and
      current state of the field.

PMID- 17014236
TI  - Microchameleons: nonlinear chemical microsystems for amplification and sensing.
AB  - In biological systems, the coupling of nonlinear biochemical kinetics and
      molecular transport enables functional sensing and "signal" amplification across
      many length scales. Drawing on biological inspiration, we describe how artificial
      reaction-diffusion (RD) microsystems can provide a basis for sensing
      applications, capable of amplifying micro- and nanoscopic events into macroscopic
      visual readouts. The RD applications reviewed here are based on a novel
      experimental technique, WETS for Wet Stamping, which offers unprecedented control
      over RD processes in microscopic and complex geometries. It is discussed how RD
      can be used to sense subtle differences in the thickness and/or absorptivity of
      thin absorptive films, amplify macromolecular phase transitions, detect the
      presence and quality of self-assembled monolayers, and provide dynamic
      spatiotemporal readouts of chemical "metabolites."

PMID- 17014238
TI  - Cooperative stochastic behavior in the onset of localized corrosion.
AB  - Stochastic temporal and spatiotemporal models of metastable pitting on a metal
      surface are presented. A stochastic reaction-diffusion model accounts for the
      effects of local changes in concentration, potential drop, and oxide film damage
      on the nucleation of subsequent events. The cooperative interactions among events
      can lead to the formation of clusters of metastable pits and to an explosive
      growth in the total number of pits. Recent progress in the studies of such
      phenomena is reviewed. New results based on a mean-field analysis of the model
      and numerical simulations on critical nucleation effects are reported.

PMID- 17014237
TI  - Magnetic resonance imaging of chemical waves in porous media.
AB  - Magnetic resonance imaging (MRI) provides a powerful tool for the investigation
      of chemical structures in optically opaque porous media, in which chemical
      concentration gradients can be visualized, and diffusion and flow properties are
      simultaneously determined. In this paper we give an overview of the MRI technique
      and review theory and experiments on the formation of chemical waves in a tubular
      packed bed reactor upon the addition of a nonlinear chemical reaction. MR images
      are presented of reaction-diffusion waves propagating in the three-dimensional
      (3D) network of channels in the reactor, and the 3D structure of stationary
      concentration patterns formed via the flow-distributed oscillation mechanism is
      demonstrated to reflect the local hydrodynamics in the packed bed. Possible
      future directions regarding the influence of heterogeneities on transport and
      reaction are discussed.

PMID- 17014239
TI  - Synchronization phenomena for a pair of locally coupled chaotic electrochemical
      oscillators: a survey.
AB  - Chaotic synchronization of two locally coupled electrochemical oscillators is
      studied numerically. Both bidirectional and unidirectional couplings are
      considered. For both these coupling scenarios, varying the characteristics of the
      coupling terms (functional form and/or strength) reveals a wide variety of
      synchronization phenomena. Standard diagnostic tests are performed to verify and
      classify the different types of synchronizations observed.

PMID- 17014240
TI  - Periodic and chaotic oscillations of the electrochemical potential of p-Si in
      contact with an aqueous (CuSO4+HF) solution, caused by electroless Cu deposition.
AB  - Periodic and chaotic oscillations were observed for the potential of p-type
      Si(111) immersed in an aqueous (HF+CuSO(4)) solution, accompanied by electroless
      Cu deposition on p-Si. They were, to our knowledge, the first examples of open
      circuit potential oscillations observed for semiconductor electrodes. The
      oscillations appeared only when the Cu deposit formed a continuous porous film
      composed of mutually connected submicrometer-sized particles. Besides, the Si
      surface was kept flat within the size less than 50 nm even after the prolonged
      oscillation for a few hours, though the Si surface should be etched considerably
      with HF for this time. A plausible model is proposed for the periodic
      oscillation, in which interestingly coupling of autocatalytic shift in the flat
      band potential of Si (U(fb)) caused by the change in the coverage of the Si oxide
      and the connection and disconnection of the Cu film with the Si surface plays the
      key role. The appearance of the chaotic oscillation is also explained by taking
      into account an oscillation-coupled change in the HF or Cu(2+) concentration near
      the Si surface.

PMID- 17014241
TI  - Oscillations, period doublings, and chaos in CO oxidation and catalytic mufflers.
AB  - Early experimental observations of chaotic behavior arising via the period
      doubling route for the CO catalytic oxidation both on Pt(110) and Ptgamma
      Al(2)O(3) porous catalyst were reported more than 15 years ago. Recently, a
      detailed kinetic reaction scheme including over 20 reaction steps was proposed
      for the catalytic CO oxidation, NO(x) reduction, and hydrocarbon oxidation taking
      place in a three-way catalyst (TWC) converter, the most common reactor for
      detoxification of automobile exhaust gases. This reactor is typically operated
      with periodic variation of inlet oxygen concentration. For an unforced lumped
      model, we report results of the stoichiometric network analysis of a CO reaction
      subnetwork determining feedback loops, which cause the oscillations within
      certain regions of parameters in bifurcation diagrams constructed by numerical
      continuation techniques. For a forced system, numerical simulations of the CO
      oxidation reveal the existence of a period-doubling route to chaos. The
      dependence of the rotation number on the amplitude and period of forcing shows a
      typical bifurcation structure of Arnold tongues ordered according to Farey
      sequences, and positive Lyapunov exponents for sufficiently large forcing
      amplitudes indicate the presence of chaotic dynamics. Multiple periodic and
      aperiodic time courses of outlet concentrations were also found in simulations
      using the lumped model with the full TWC kinetics. Numerical solutions of the
      distributed model in two geometric coordinates with the CO oxidation subnetwork
      consisting of several tens of nonlinear partial differential equations show
      oscillations of the outlet reactor concentrations and, in the presence of
      forcing, multiple periodic and aperiodic oscillations. Spatiotemporal
      concentration patterns illustrate the complexity of processes within the reactor.

PMID- 17014242
TI  - Nonequilibrium self-organization phenomena in active Langmuir monolayers.
AB  - Langmuir monomolecular layers, formed by amphiphilic molecules at liquid-air
      interfaces and containing a fraction of chiral molecules, are theoretically
      investigated. These monolayers can be brought out of thermal equilibrium by
      applying a gradient of small molecules across the interface, resulting in the
      leakage flow. We show that, when splay coupling between the orientation field and
      the local concentration of chiral molecules in the monolayer is taken into
      account, this nonequilibrium soft matter system can show complex wave behavior,
      including the development of target wave patterns, spiral waves, and dense
      regions filled with inwardly propagating waves.

PMID- 17014243
TI  - Spatio-temporal behaviors of a clock reaction in an open gel reactor.
AB  - The concentration profiles along the feeding direction of a one side fed gel
      reactor are analyzed for the iodate-arsenous acid reaction. Multiplicity of
      inhomogeneous stationary solutions is derived. It is also shown that such
      profiles may undergo oscillatory bifurcations under long range activation
      conditions. The bifurcation diagram is analyzed using a Galerkin approximation,
      the asymptotic validity of which is discussed.

PMID- 17014244
TI  - Spatial bistability: a source of complex dynamics. From spatiotemporal reaction
      diffusion patterns to chemomechanical structures.
AB  - We show experimentally and theoretically that reaction systems characterized by a
      slow induction period followed by a fast evolution to equilibrium can readily
      generate "spatial bistability" when operated in thin gel reactors diffusively fed
      from one side. This phenomenon which corresponds to the coexistence of two
      different stable steady states, not breaking the symmetry of the boundary
      conditions, can be at the origin of diverse reaction-diffusion instabilities.
      Using different chemical reactions, we show how stationary pulses, labyrinthine
      patterns or spatiotemporal oscillations can be generated. Beyond simple reaction
      diffusion instabilities, we also demonstrate that the cross coupling of spatial
      bistability with the size responsiveness of a chemosensitive gel can give rise to
      autonomous spatiotemporal shape patterns, referred to as chemomechanical
      structures.

PMID- 17014245
TI  - Emergent reaction-diffusion phenomena in capillary tubes.
AB  - Pattern formation in the Belousov-Zhabotinsky reaction experiments carried out by
      filling capillary glass tubes with catalyst-immobilized gel for the reaction is
      reported. Under unperturbed and oscillatory conditions, helicoidal waves appear
      spontaneously. Quantitative structural data of those helices are obtained by
      devising an optical tomography technique for extracting rotationally symmetric
      structures from time-lapse data. Space-time representation of the catalyst
      oxidation reveals wave transmission phenomenon that is studied further by
      numerical simulations of a reduced spatial model.

PMID- 17014246
TI  - Propagation failures, breathing pulses, and backfiring in an excitable reaction
      diffusion system.
AB  - We report results from experiments with a pseudo-one-dimensional Belousov
      Zhabotinsky reaction that employs 1,4-cyclohexanedione as its organic substrate.
      This excitable system shows traveling oxidation pulses and pulse trains that can
      undergo complex sequences of propagation failures. Moreover, we present examples
      for (i) breathing pulses that undergo periodic changes in speed and size and (ii)
      backfiring pulses that near their back repeatedly generate new pulses propagating
      in opposite direction.

PMID- 17014247
TI  - Resonant and nonresonant patterns in forced oscillators.
AB  - Uniform oscillations in spatially extended systems resonate with temporal
      periodic forcing within the Arnold tongues of single forced oscillators. The
      Arnold tongues are wedge-like domains in the parameter space spanned by the
      forcing amplitude and frequency, within which the oscillator's frequency is
      locked to a fraction of the forcing frequency. Spatial patterning can modify
      these domains. We describe here two pattern formation mechanisms affecting
      frequency locking at half the forcing frequency. The mechanisms are associated
      with phase-front instabilities and a Turing-like instability of the rest state.
      Our studies combine experiments on the ruthenium catalyzed light-sensitive
      Belousov-Zhabotinsky reaction forced by periodic illumination, and numerical and
      analytical studies of two model systems, the FitzHugh-Nagumo model and the
      complex Ginzburg-Landau equation, with additional terms describing periodic
      forcing.

PMID- 17014248
TI  - Turing patterns beyond hexagons and stripes.
AB  - The best known Turing patterns are composed of stripes or simple hexagonal
      arrangements of spots. Until recently, Turing patterns with other geometries have
      been observed only rarely. Here we present experimental studies and mathematical
      modeling of the formation and stability of hexagonal and square Turing
      superlattice patterns in a photosensitive reaction-diffusion system. The
      superlattices develop from initial conditions created by illuminating the system
      through a mask consisting of a simple hexagonal or square lattice with a
      wavelength close to a multiple of the intrinsic Turing pattern's wavelength. We
      show that interaction of the photochemical periodic forcing with the Turing
      instability generates multiple spatial harmonics of the forcing patterns. The
      harmonics situated within the Turing instability band survive after the
      illumination is switched off and form superlattices. The square superlattices are
      the first examples of time-independent square Turing patterns. We also
      demonstrate that in a system where the Turing band is slightly below criticality,
      spatially uniform internal or external oscillations can create oscillating square
      patterns.

PMID- 17014249
TI  - Spiral wave dynamics in excitable media with spherical geometries.
AB  - We describe the spatial and temporal organization of spiral and scroll waves in
      spherical shells of different sizes and solid spheres. We present simulation
      results for the evolution of the dynamics and clustering of spiral waves as a
      function of the excitability of the medium. The excitability, topology, and size
      of the domain places restrictions on how single and multiarmed spiral waves are
      organized in space. The results in spherical geometries are compared with those
      in planar two-dimensional media. These studies are relevant to the dynamics of
      spiral waves in a variety of media including the heart, and chemical reactions on
      spherical surfaces.

PMID- 17014250
TI  - Experimental evidence and theoretical analysis for the chiral symmetry breaking
      in the growth front of conglomerate crystal phase of 1,1'-binaphthyl.
AB  - Chirally asymmetric states, chemical oscillations, propagating chemical waves,
      and spatial patterns, are examples of far-from-equilibrium self-organization. We
      have found that the crystal growth front of 1,1(')-binaphthyl shows many of the
      characteristics of an open system in which chiral symmetry breaking has occurred.
      From its supercooled molten phase, 1,1(')-binaphthyl crystallizes as a
      conglomerate of R and S crystals when the temperature is above 145 degrees C. In
      addition, 1,1(')-binaphthyl in its molten phase is always racemic due to its high
      racemization rate. Under appropriate conditions, bimodal probability distribution
      of enantiomeric excess (ee) with maxima around 60% was observed. The ee was mass
      independent, indicating that the growth front maintains a constant ee. A kinetic
      model that theoretically analyzes the chiral symmetry breaking transition in the
      growth front of a conglomerate crystal phase was formulated. Computer simulation
      of the model reproduced not only the average but also the large variation of the
      ee observed in crystallization experiments.

PMID- 17014252
TI  - Primes and targets in rapid chases: tracing sequential waves of motor activation.
AB  - Single-cell recordings have indicated that visual stimuli elicit rapid waves of
      neuronal activation that propagate so fast that they might be free of
      intracortical feedback. Here, the time course of feedforward activation was
      traced by measuring pointing responses to color targets preceded by color primes
      initiating either the same or opposite response. The early time course of priming
      effects was strictly time locked to prime onset and depended only on properties
      of the primes, but was independent of the onset times of the actual targets as
      well as the perceptual effects of targets on primes. Results indicated that
      nonoverlapping feedforward signals by primes and targets traverse the visuomotor
      system in a rapid chase, controlling associated motor responses in strict
      sequence.

PMID- 17014251
TI  - Contingency awareness and fear inhibition in a human fear-potentiated startle
      paradigm.
AB  - Fear-potentiated startle is defined as an increase in the magnitude of the
      startle reflex in the presence of a stimulus that was previously paired with an
      aversive event. It has been proposed that a subject's awareness of the
      contingencies in the experiment may affect fear-potentiated startle. The authors
      adapted a conditional discrimination procedure (AX+/BX-), previously validated in
      animals, to a human fear-potentiated startle paradigm in 50 healthy volunteers.
      This paradigm allows for an assessment of fear-potentiated startle during threat
      conditions as well as inhibition of fear-potentiated startle during safety
      conditions. A response keypad was used to assess contingency awareness on a trial
      by-trial basis. Both aware and unaware subjects showed fear-potentiated startle.
      However, awareness was related to stimulus discrimination and fear inhibition.

PMID- 17014253
TI  - Early maternal rejection affects the development of monoaminergic systems and
      adult abusive parenting in rhesus macaques (Macaca mulatta).
AB  - This study investigated the effects of early exposure to variable parenting style
      and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine
      metabolites and examined the role of monoaminergic function in the
      intergenerational transmission of infant abuse in rhesus monkeys (Macaca
      mulatta). Forty-three infants reared by their biological mothers and 15 infants
      that were cross-fostered at birth and reared by unrelated mothers were followed
      longitudinally through their first 3 years of life or longer. Approximately half
      of the infants were reared by abusive mothers and half by nonabusive controls.
      Abused infants did not differ from controls in CSF concentrations of 5
      hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4
      hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates
      of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA
      than low-rejection infants. The abused females who became abusive mothers in
      adulthood had lower CSF 5-HIAA than the abused females who did not. A similar
      trend was also observed among the cross-fostered females, suggesting that low
      serotonergic function resulting from early exposure to high rates of maternal
      rejection plays a role in the intergenerational transmission of infant abuse.

PMID- 17014255
TI  - Prefrontal control of trace versus delay eyeblink conditioning: role of the
      unconditioned stimulus in rabbits (Oryctolagus cuniculus).
AB  - The conditioned eyeblink (EB) response was studied with trace conditioning
      procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial
      prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in
      which either periorbital shock or a corneal airpuff served as the unconditioned
      stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of
      the EB conditioned response (CR) was faster and reached a higher asymptote with
      the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace
      conditioning deficits were obtained only in the groups that received the airpuff
      US. All rabbits showed normal delay conditioning and extinction. These results
      suggest that mPFC mediates trace EB conditioning when emotional arousal is low.
      However, in circumstances when emotional arousal may be high (i.e., during
      exposure to aversive periorbital shock), other structures (such as amygdala) may
      be activated to permit learning even in the absence of input from mPFC.

PMID- 17014254
TI  - Sex and handedness effects on corpus callosum morphology in chimpanzees (Pan
      troglodytes).
AB  - Findings suggest that in humans, sex and hand preference may be associated with
      the size of the corpus callosum (CC). The authors measured CC morphology from
      MRIs in 67 chimpanzees (Pan troglodytes) to see whether similar effects were
      present in this species. Hand preference was assessed by performance on 4 tasks,
      and chimpanzees were classified as left-handed, right-handed, or ambidextrous. In
      a subsequent analysis, the chimpanzees were reclassified into 2 groups: right
      handed and left-handed. The results revealed no sex difference in CC area, but
      significant effects of hand preference were found for several CC regions (rostrum
      body, anterior midbody, posterior midbody, isthmus, and splenium) and for overall
      CC size, with left-handed chimpanzees exhibiting significantly smaller CC
      measurements than right-handed chimpanzees. The results indicate that lateralized
      hand use in chimpanzees, as in humans, is associated with variation in CC size.

PMID- 17014256
TI  - Evolution of cerebral cortex involvement in the acquisition of associative
      learning.
AB  - The presence of the c-Fos protein has been evidenced in the piriform cortex,
      subiculum, entorhinal and perirhinal cortices, and parietal and occipital
      cortices at different stages (Sessions 2, 4, and 6) in the acquisition of a trace
      conditioning in behaving rabbits. c-Fos immunostaining was also measured after a
      reminder (7th) session. c-Fos immunoreactivity increased significantly across
      conditioning on the contralateral side of the piriform, entorhinal, perirhinal,
      and parietal cortices as compared with the ipsilateral side of conditioned
      animals and the contralateral side of pseudo-conditioned ones. No difference in c
      Fos immunostaining was observed between contra- and ipsilateral sides in the
      subiculum of conditioned animals. c-Fos production decreased significantly across
      conditioning but presented a noticeable bilateral increase after the reminder
      session in the piriform, entorhinal, perirhinal, and parietal cortices, but not
      in the subiculum. Peak production of c-Fos was observed after the 2nd and 7th
      (reminder) conditioning sessions for the piriform, entorhinal, perirhinal, and
      parietal cortices, and after the 4th session for the subiculum. It is proposed
      that different cortical areas process associative learning with different
      strengths and side dominances.

PMID- 17014257
TI  - The ontogeny of interstimulus interval (ISI) discrimination of the conditioned
      eyeblink response in rats.
AB  - Discrimination of the eyeblink conditioned response (CR) between conditioned
      stimuli (CSs) of different durations and modalities was examined across
      development in rats. Interstimulus interval (ISI) discrimination was evident at
      Postnatal Days 23-34 in Experiment 1, and earlier CR peak latencies and enhanced
      CR amplitudes were seen to the long CS in the ISI discrimination group relative
      to a control group receiving the short CS without reinforcement. Experiment 2
      showed that early CR peak latencies and enhanced CR amplitudes to the long CS in
      the ISI discrimination group were due to associative pairing of the short CS and
      unconditioned stimulus. Experiment 3 demonstrated ISI discrimination in adults
      that was improved relative to younger subjects, but with no enhancement of CR
      amplitude to the long CS in the ISI discrimination group. Cerebellar cortical
      maturation may influence the ontogeny of CR timing.

PMID- 17014258
TI  - NMDA receptor antagonism impairs reversal learning in developing rats.
AB  - Four experiments examined the effect of dizocilpine maleate (MK-801), a
      noncompetitive N-methyl-Daspartate (NMDA) receptor antagonist, on reversal
      learning during development. On postnatal days (PND) 21, 26, or 30, rats were
      trained on spatial discrimination and reversal in a T-maze. When MK-801 was
      administered (intraperitoneally) before both acquisition and reversal, 0.18 mg/kg
      generally impaired performance, whereas doses of 0.06 mg/kg and 0.10 mg/kg, but
      not 0.03 mg/kg, selectively impaired reversal learning (Experiments 1 and 3). The
      selective effect on reversal was not a result of sensitization to the second dose
      of MK-801 (Experiment 2) and was observed when the drug was administered only
      during reversal in an experiment addressing state-dependent learning (Experiment
      4). Spatial reversal learning is more sensitive to NMDA-receptor antagonism than
      is acquisition. No age differences in sensitivity to MK-801 were found between
      PND 21 and 30.

PMID- 17014259
TI  - Differential responsiveness to fluoxetine during puberty.
AB  - In male golden hamsters (Mesocricetus auratus), attack frequency decreases during
      puberty. As serotonin inhibits offensive responses in adult hamsters, it is
      hypothesized that the serotonin system becomes upregulated in the hypothalamus
      during puberty. This hypothesis was tested through acute treatment with
      fluoxetine, a serotonin reuptake inhibitor, as well as through analysis of
      serotonin innervation in specific brain areas. In adults, fluoxetine treatment
      inhibited aggressive behavior. In juveniles, high doses of fluoxetine only
      reduced offensive responses (i.e., frequency and repetition of attacks), whereas
      low doses enhanced them. Juveniles also showed a dose-specific maturation of
      attack targets. In addition, the density of serotonin innervation of the
      hypothalamus was 20% higher in adult hamsters compared with juveniles. On the
      basis of these data, it is proposed that the developing serotonergic system
      shapes the development of offensive behaviors in male golden hamsters.

PMID- 17014260
TI  - Microinfusions of neurotensin antagonist SR 48692 within the nucleus accumbens
      core impair spatial learning in rats.
AB  - The involvement of neurotensin (NT) within the nucleus accumbens core (NAC) in
      behavior has been sparsely investigated. Moreover, little is known of what role
      NT within the ventral striatum has on spatial learning. The present study
      investigated whether NT receptors in the NAC are implicated in learning of
      spatial information. Male Long-Evans rats were trained on a food search spatial
      learning task. Rats were microinfused with either NT antagonist SR 48692 (50
      nM/0.5 =L) or saline in the NAC before each training session. Rats treated with
      SR 48692 made more reference and working memory errors during the acquisition of
      spatial learning than did rats infused with saline. These results suggest that NT
      receptors contribute to NAC-mediated spatial learning.

PMID- 17014262
TI  - Spatial location is critical for conditioning place preference with visual but
      not tactile stimuli.
AB  - The roles of visual, tactile, and spatial location cues were studied in 6
      conditioned place preference (CPP) experiments with ethanol (2 g/kg) in mice (of
      the DBA/2J strain). Visual cues were effective conditioned stimuli (CSs) when
      consistently presented in the same spatial location, but not when the same cue
      was presented in two different locations during training. In contrast, tactile
      CSs were effective regardless of spatial location during training. Moreover,
      spatial location controlled CPP expression when visual cues were used but not
      when tactile cues were used. However, spatial location per se was not an
      effective CS. These studies suggest that CPP conditioned to tactile cues is
      mediated by brain systems different from those mediating CPP conditioned to
      visual-spatial cues.

PMID- 17014261
TI  - Intra-ventral pallidal glutamate antagonists block expression of morphine-induced
      place preference.
AB  - The role of ionotropic glutamate receptors within the ventral pallidum (VP) in
      the expression of conditioned place preference (CPP) and motor adaptations to
      morphine was evaluated. VP-cannulated rats were subjected to 3 days of
      conditioning in which saline was paired to one distinct chamber in the morning
      and morphine (8 mg/kg ip or its vehicle) was paired to an alternate chamber in
      the afternoon. This induced (a) CPP expression in drug-free rats 1 day later,
      which was blocked by immediate pretreatments with intra-VP injections of a
      glutamate antagonist cocktail (DL-2-amino-5- phosphonopentanoic acid lithium salt
      [AP-5] + 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt [CNQX]), and (b)
      changes in motor function expressed following an acute morphine challenge 18 days
      later, which were absent if preceded by a 10-day treatment with the glutamate
      antagonists injected unilaterally once daily in alternating hemispheres. Thus, VP
      ionotropic glutamate receptors are critical mediators of the expression of place
      preference and motor adaptations subsequent to repeated morphine exposure.

PMID- 17014263
TI  - Reduced hedonic behavior and altered cardiovascular function induced by mild
      sodium depletion in rats.
AB  - Interactions among sodium homeostasis, fatigue, mood, and cardiovascular
      regulation have been described previously. The present study investigates the
      effects of sodium deficiency on an index of mood (hypohedonia; Experiment 1),
      cardiovascular function (Experiment 2), and plasma electrolytes (Experiment 3) in
      rats. Following 48 hr of sodium depletion with a diuretic (furosemide) and a
      sodium deficient diet, rats displayed hypohedonia evidenced by reduced responding
      for rewarding electrical brain stimulation into the hypothalamus. Also, sodium
      depletion produced increased heart rate and reduced heart rate variability.
      Plasma sodium levels were lower in sodium-depleted rats versus control rats,
      whereas potassium levels were unchanged. Thus, mild sodium depletion produces
      hypohedonia and cardiovascular alterations, which has implications for
      understanding behavioral and cardiovascular consequences of sodium deficiency.

PMID- 17014264
TI  - Conditioning following repeated exposure to MDMA in rats: role in the maintenance
      of MDMA self-administration.
AB  - There has been some controversy in the literature concerning the ability of +/
      3,4 methylenedioxymethamphetamine (MDMA) to reinforce operant responding in rats.
      In the present study, operant responding maintained by intravenous MDMA infusions
      increased when the fixed ratio schedule was increased from 1 to 5, decreased when
      saline was substituted for MDMA, and increased again when MDMA was reintroduced.
      During self-administration training, each infusion of MDMA was paired with the
      illumination of a light stimulus. The role of the continued presentation of this
      drug-associated stimulus in operant responding was measured in groups of rats
      that had received comparable exposure (average 19 daily test sessions) to MDMA
      during training. When either the light stimulus or the drug infusion was omitted,
      operant responding decreased gradually over the 15-day test period following
      training. When both the light stimulus and the MDMA infusion were omitted, there
      was a dramatic decrease in operant responding that persisted for the entire 15
      day test period. These findings suggest that cues associated with MDMA develop
      conditioned properties that might contribute to drug taking.

PMID- 17014265
TI  - Effects of dorsal and ventral vertical lobe electrolytic lesions on spatial
      learning and locomotor activity in Sepia officinalis.
AB  - This study aims to analyze the effects of electrolytic lesion, restricted to
      either the ventral or the dorsal parts of the vertical lobe (VL), on the behavior
      of cuttlefish (Sepia officinalis). Two behavioral tests were performed on sham
      operated and lesioned cuttlefish: assessment of locomotor activity in an open
      field and determination of spatial learning abilities in a T maze. The results
      showed that ventral lesions of the VL led to marked impairment in the acquisition
      of spatial learning, whereas dorsal lesions of the VL increased locomotor
      activity in the open field and impaired long-term retention of spatial learning.
      This study establishes for the first time the existence of distinct functions in
      the ventral and the dorsal parts of the VL in cephalopods.

PMID- 17014266
TI  - D-cycloserine facilitates extinction but does not eliminate renewal of the
      conditioned emotional response.
AB  - The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear
      was investigated in rats using the conditioned emotional response preparation.
      Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg
      dose of DCS. However, extinguished fear was "renewed" regardless of the drug
      treatment when the rats were returned to the context in which fear had been
      conditioned. Additional results suggest that DCS's facilitation of extinction is
      a small but meaningful effect in the current method. The results suggest caution
      regarding the use of DCS as an adjunct to extinction: Although the drug may
      modestly facilitate extinction learning, it does not necessarily destroy the
      potential for relapse. Behavioral mechanisms are discussed.

PMID- 17014267
TI  - Modeling the effects of the NMDA receptor antagonist MK-801 on timing in rats.
AB  - The NMDA receptor antagonist MK-801 produces different effects on timing tasks.
      In particular, MK-801 produces an underestimation of duration when animals are
      tested with the differential reinforcement of low rate of responding (DRL)
      schedule and an overestimation of duration when animals are tested with the peak
      interval (PI) procedure. The goal of this study was to develop a model-based
      explanation for this discrepancy. Two computer simulations were conducted via an
      implementation of scalar expectancy theory (SET). In Simulation 1, SET was used
      to provide a quantitative account of PI timing data. Simulation 2 used parameter
      estimates from Simulation 1 to predict effects of MK-801 on the DRL task. DRL
      predictions provided a close match to previous empirical data. Results of the
      simulations suggest that differences in the literature are likely due to inherent
      differences between PI and DRL tasks, rather than fundamental differences in
      timing. Overall, the role of NMDA receptors in timing appears to be multifaceted,
      impacting perception, memory, and decision processes.

PMID- 17014268
TI  - Altered responsivity to central administrations of corticotropin-releasing factor
      in rats with a history of opiate exposures.
AB  - The authors studied the effects of a history of opiate exposures on behavioral
      responses to intracerebroventricular (ICV) microinjections of the stress-related
      peptide corticotropin-releasing factor (CRF). Rats were injected for 10 days with
      morphine (10 mg/kg) or saline, and 1 or 7 days later they received an ICV
      microinjection of CRF (0.5 microg or 2.5 microg) or artificial cerebrospinal
      fluid. Microinjections of CRF produced anxiety-like behavior, locomotor activity,
      and self-grooming. The anxiogenic response was altered so that morphine-treated
      rats showed reduced responses to 0.5-microg CRF but showed exaggerated responses
      to 2.5-microg CRF 1 or 7 days after last opiate exposure. These findings suggest
      that alterations in central CRF circuits may underpin the increased vulnerability
      to anxiety observed following opiate exposures.

PMID- 17014269
TI  - Olfactory repeated discrimination reversal in rats: effects of chlordiazepoxide,
      dizocilpine, and morphine.
AB  - Effects of a benzodiazepine (chlordiazepoxide), an N-methyl-D-aspartate receptor
      antagonist (dizocilpine), and an opiate agonist (morphine) were studied with a
      procedure designed to assess effects of drugs and other manipulations on
      nonspatial learning in rats. In each session, rats were exposed to 2 different 2
      choice odor-discrimination problems with food reinforcement for correct
      responses. One problem (performance discrimination) remained the same throughout
      the study. That is, 1 odor was always correct (S+) and the other was never
      correct (S-). For the other problem (reversal discrimination), stimuli changed
      every session. Six different odors were used to program the reversal
      discrimination; on any given session, S+ was a stimulus that had served as S- the
      last time it had appeared, S- was a stimulus that had been S+ on its last
      appearance. Thus, in each session, learning a discrimination reversal could be
      studied along with the performance of a comparable, but previously learned,
      discrimination. Chlordiazepoxide interfered with reversal learning at doses that
      had no effect on the performance discrimination. Morphine and dizocilpine also
      impaired reversal learning but only at doses that also affected performance of
      the well-learned performance discrimination.

PMID- 17014270
TI  - Selective involvement of the lateral entorhinal cortex in the control of the
      olfactory memory trace during conditioned odor aversion in the rat.
AB  - Evidence from the effect of aspiration lesions of the entorhinal cortex (EC) has
      shown that this region is involved in conditioned odor-aversion (COA) learning-
      that is, the avoidance of an odorized tasteless solution the ingestion of which
      precedes toxicosis--by rendering COA tolerant to long odor-toxicosis delay. The
      present study examined whether neurotoxic lesions restricted to the lateral or
      medial parts of the EC, in comparison with large aspiration lesions, were
      sufficient to produce this effect. Male Long-Evans rats received odor
      intoxication pairing with either a short (5-min) or long (120-min) delay between
      the presentation of the odor and toxicosis. All groups, including sham-lesioned
      controls, showed COA at the 5-min odor-toxicosis delay interval, but only rats
      with lateral EC damage displayed COA at the longer delay. These data show that
      the lateral EC is part of the substrate involved in the control of the olfactory
      memory trace during COA.

PMID- 17014271
TI  - A meta-analysis of teen cigarette smoking cessation.
AB  - OBJECTIVE: This article presents a meta-analysis of 48 teen cigarette smoking
      cessation studies, the 1st meta-analysis of its kind. The authors conducted
      searches of electronic databases and unpublished manuscripts from 1970 to 2003.
      Fifty contextual elements were coded from each article. A weighted least squares
      random effects method was used to pool results from individual study net effects
      estimates. Multilevel random coefficients modeling was applied to control for the
      intrastudy variation. MAIN OUTCOME MEASURES: The primary outcome for the present
      analysis was quit rate. Data were entered as intent-to-treat (ITT) quit rates
      (not compliance sample rates). Overall treatment effect size and treatment effect
      sizes as a function of program content, modality, number of sessions, and length
      of follow-up were examined. RESULTS: Across studies, program conditions, compared
      with control conditions, appeared to give smokers a 2.90% (95% confidence
      interval = 1.47-4.35%) absolute advantage in quitting, increasing the probability
      of quitting by approximately 46% (9.14% vs. 6.24%). Relatively higher quit rates
      were found in programs that included a motivation enhancement component,
      cognitive-behavioral techniques, and social influence approaches. Also,
      relatively higher quit rates were found in school-based clinic and classroom
      modalities. Furthermore, relatively higher quit rates were found for programs
      consisting of at least 5 quit sessions. Data also indicated that the effects were
      maintained at short-term (1 year or less) and longer term (longer than 1 year)
      follow-ups. CONCLUSION: Much more teen smoking cessation research is needed, but
      teen smoking cessation programming is effective, and the present study provides a
      framework to move forward.

PMID- 17014272
TI  - Evidence for clinical smoking cessation for adolescents.
AB  - OBJECTIVE: This report reviews the evidence that informs the role of health and
      mental health care providers in addressing youth smoking cessation. DESIGN:
      Qualitative literature review. RESULTS: Physicians do not consistently screen
      adolescents for tobacco use and fail to provide recommended cessation advice.
      Challenges to addressing smoking cessation include the need for procedures to
      ensure confidentiality and the existence of competing demands to provide other
      services. Few published studies have specifically addressed the effectiveness of
      clinical interventions. Interventions that require return visits or follow-up
      phone contacts are technically difficult to implement in this population.
      Successful interventions may require resources not available in nonresearch
      settings. Most studies have used brief clinical intervention as a control
      condition, making it impossible to evaluate its effectiveness. CONCLUSION: There
      is little evidence that supports current clinical smoking cessation guidelines
      for adolescents. More research is needed to develop inexpensive, efficient
      clinical interventions that can provide youths access to smoking cessation help.
      Future challenges include reorganizing clinical systems to offer greater
      counseling by support staff or in electronic formats and to provide effective
      booster messages and follow-up care in a population that is difficult to track.

PMID- 17014273
TI  - A randomized controlled trial of a coping group intervention for adults with HIV
      who are AIDS bereaved: longitudinal effects on grief.
AB  - The authors sought to study the longitudinal effects of a cognitive-behavioral
      group intervention for coping with AIDS bereavement among a diverse sample of
      adults who were HIV positive. Participants (N = 267) were randomly assigned to
      receive the 12-week intervention or individual therapy upon request. Measures
      were administered at baseline, postintervention, and 4-, 8-, and 12-month follow
      ups. Longitudinal data were analyzed with linear mixed models to examine change
      in grief by condition across the study period and the effect of the intervention
      on grief through its interaction with psychiatric distress. The authors used the
      Grief Reaction Index to assess grief and the Symptom Checklist-90-Revised to
      assess global psychiatric distress. Participants in both conditions reported
      decreases in grief severity. However, among those with higher levels of
      psychiatric distress, participants in the group intervention had significantly
      lower grief severity scores compared with participants in the individual therapy
      condition. The long-term effectiveness of this AIDS-bereavement intervention for
      psychiatrically distressed people with HIV/AIDS supports the need for tailored
      interventions among those at risk for complicated grief responses.

PMID- 17014274
TI  - Being controlled by normative influences: self-determination as a moderator of a
      normative feedback alcohol intervention.
AB  - The objectives of this research were to evaluate the efficacy of computer
      delivered personalized normative feedback among heavy drinking college students
      and to evaluate controlled orientation as a moderator of intervention efficacy.
      Participants (N = 217) included primarily freshman and sophomore, heavy drinking
      students who were randomly assigned to receive or not to receive personalized
      normative feedback immediately following baseline assessment. Perceived norms,
      number of drinks per week, and alcohol-related problems were the main outcome
      measures. Controlled orientation was specified as a moderator. At 2-month follow
      up, students who received normative feedback reported drinking fewer drinks per
      week than did students who did not receive feedback, and this reduction was
      mediated by changes in perceived norms. The intervention also reduced alcohol
      related negative consequences among students who were higher in controlled
      orientation. These results provide further support for computer-delivered
      personalized normative feedback as an empirically supported brief intervention
      for heavy drinking college students, and they enhance the understanding of why
      and for whom normative feedback is effective.

PMID- 17014275
TI  - Interactive but not direct effects of perceived racism and trait anger predict
      resting systolic and diastolic blood pressure in black adolescents.
AB  - This correlation study explicated the association of perceived racism and trait
      anger to resting blood pressure in a high school sample of 234 Blacks. Perceived
      racism and trait anger were assessed via self-report, and resting blood pressure
      was measured with a noninvasive blood pressure monitor. Hierarchical regression
      analyses indicated that perceived racism and trait anger were not independent
      predictors of systolic or diastolic blood pressure. However, these analyses
      revealed that the interactive effects of perceived racism and trait anger were
      predictive of systolic and diastolic blood pressure. Although perceived racism
      was not significantly related to blood pressure among those who were high in
      trait anger, perceived racism was inversely associated with blood pressure among
      those who were low in trait anger. The findings may have important longer term
      implications for future research examining the contribution of psychosocial
      factors to cardiac and vascular functioning in Blacks.

PMID- 17014276
TI  - "When no means no": can reactance augment the theory of planned behavior?
AB  - A longitudinal study examined women's clinic attendance for treatment and follow
      up after having received an abnormal cervical screening result. Participants (N =
      660) completed questionnaire measures of variables specified by the theory of
      planned behavior and J. Kuhl's (2000) measure of low volitional control-
      reactance--prior to receiving up to 3 subsequent appointments during the
      following 15 months. The theory of planned behavior was capable of predicting
      persistent attendance and discriminated women who kept all of their scheduled
      appointments from those who dropped out from treatment. Consideration of
      reactance enhanced prediction of behavior and discriminated between women who
      delayed appointment keeping and women who ceased attending.

PMID- 17014277
TI  - Impact of a social influence intervention on condom use and sexually transmitted
      infections among establishment-based female sex workers in the Philippines: a
      multilevel analysis.
AB  - The authors assessed the relative impact of structural and social influence
      interventions on reducing sexually transmitted infections (STIs) and HIV risk
      behavior among female sex workers in the Philippines (N = 897). Four conditions
      included manager influence, peer influence, combined manager-peer influence, and
      control. Intervention effects were assessed at the establishment level in
      multilevel models because of statistical dependencies among women employed within
      the same establishments. Control group membership predicted greater perceived
      risk, less condom use, less HIV/AIDS knowledge, and more negative condom
      attitudes. Combination participants reported more positive condom attitudes, more
      establishment policies favoring condom use, and fewer STIs. Manager-only
      participants reported fewer STIs, lower condom attitudes, less knowledge, and
      higher perceived risk than peer-only participants. Because interventions were
      implemented at the city level, baseline and follow-up city differences were
      analyzed to rule out intervention effects due to preexisting differences.

PMID- 17014278
TI  - Comparing two theories of health behavior: a prospective study of noncompletion
      of treatment following cervical cancer screening.
AB  - Some women receiving abnormal cervical screening tests do not complete
      recommended treatment. A prospective study (N = 660) investigated the value of
      conceptualizing attendance at colposcopy for treatment as either (a) an active
      problem-solving response to a health threat, motivated by attitudes toward an
      abnormal result, as implied by self-regulation theory (H. Leventhal, D. Meyer, &
      D. Nerenz, 1980); or (b) as a behavior motivated by attitudes toward clinic
      attendance, as implied by the theory of planned behavior (TPB; I. Ajzen, 1985).
      Responses to questionnaires containing variables specified by these models were
      used to predict women's subsequent attendance or nonattendance for treatment over
      the following 15 months. Although the TPB offered superior prediction of
      intentions and completion of treatment, discriminant function analyses showed
      that consideration of both models was important in distinguishing between those
      who attended all their appointments as scheduled, attended after being prompted,
      or ceased attending. Implications for measurement and theory in health protection
      are discussed.

PMID- 17014279
TI  - Mediation of a middle school skin cancer prevention program.
AB  - This study tested potential mediators of a school-based skin cancer prevention
      intervention for middle school children (6th-8th grades; N = 1,788). Ten
      variables were tested on 4 criteria to establish mediation, including (a)
      intervention related to outcome, (b) intervention related to mediators, (c)
      mediators related to outcome, and (d) mediated effect statistically significant.
      Sun-safe behaviors (e.g., sunscreen use) and potential mediators were measured
      with a self-report questionnaire. All criteria were met for Barriers--Sunscreen,
      Perceived Self-Efficacy, and Knowledge when the mediators were tested separately.
      In multiple mediator analyses, barriers to sunscreen use and self-efficacy
      satisfied Criteria 1-3 but were not statistically significant (Criterion 4).
      Barriers to sunscreen use, perceived self-efficacy for sun-safe behavior, and
      knowledge may serve as mediators.

PMID- 17014280
TI  - Specifying the determinants of the initiation and maintenance of behavior change:
      an examination of self-efficacy, satisfaction, and smoking cessation.
AB  - Using data from smokers (N = 591) who enrolled in an 8-week smoking cessation
      program and were then followed for 15 months, the authors tested the thesis that
      self-efficacy guides the decision to initiate smoking cessation but that
      satisfaction with the outcomes afforded by quitting guides the decision to
      maintain cessation. Measures of self-efficacy and satisfaction assessed at the
      end of the program, 2 months, and 9 months were used to predict quit status at 2,
      9, and 15 months, respectively. At each point, participants were categorized as
      either initiators or maintainers on the basis of their pattern of cessation
      behavior. Across time, self-efficacy predicted future quit status for initiators,
      whereas satisfaction generally predicted future quit status for maintainers.
      Implications for models of behavior change and behavioral interventions are
      discussed.

PMID- 17014281
TI  - The toll of ethnic discrimination on sleep architecture and fatigue.
AB  - Most work on ethnicity tends to focus on daytime health rather than how aspects
      of ethnicity affect nighttime functioning. The current study examined how
      discrimination and ethnic identity relate to sleep architecture and fatigue in 37
      African Americans and 56 Caucasian Americans. The authors conducted sleep
      monitoring with standard polysomnography. African Americans had less slow-wave
      sleep and reported more physical fatigue than did Caucasian Americans (ps < .05).
      The authors conducted path analyses to examine relationships between ethnic
      identity, perceived discrimination, sleep, and fatigue. Perceived discrimination
      mediated ethnic differences in Stage 4 sleep and physical fatigue. Individuals
      who reported experiencing more discrimination had less Stage 4 sleep and reported
      experiencing greater physical fatigue (ps < .05). Although ethnic identity did
      not mediate ethnic differences in sleep latency, there was a significant
      relationship between ethnic identity and sleep latency, indicating that
      individuals who felt more connected to their ethnic group had more difficulty
      falling asleep while in the hospital (p < .05). These observations suggest that
      the effects of stress related to one's ethnic group membership carry over into
      sleep.

PMID- 17014282
TI  - Facial disfigurement in patients with head and neck cancer: the role of social
      self-efficacy.
AB  - This study investigated the moderating role of social self-efficacy (i.e., the
      belief that one is capable of exercising control over the reactions and openness
      of other people) with respect to the link between facial disfigurement and
      psychological and n = 76) as well as their physicians. In line with the
      hypotheses, the results revealed that the degree of facial disfigurement, as
      judged by patients as well as their physicians, was positively related to
      psychological distress and distress in reaction to unpleasant behavior of others,
      but only when patients did not feel self-efficacious in social encounters.
      Furthermore, social self-efficacy mitigated the positive link between facial
      disfigurement as judged by patients and social isolation.

PMID- 17014283
TI  - Transtheoretical model and condom use in HIV-positive youths.
AB  - The purpose of the study is to test constructs of the Transtheoretical Model for
      predicting unprotected intercourse in HIV-positive youths (ages 16-25 years).
      Questionnaires and interviews about sexual behavior, stage of change, self
      efficacy, substance use, emotional distress, and social support were obtained
      from 60 HIV-positive youths. Path analysis, with standard errors determined by
      methods appropriate to small samples, suggested that self-efficacy completely
      mediated the relationship between stage of change and unprotected intercourse
      acts. Social support specific to reducing risk was associated with increased self
      efficacy. Emotional distress and low general social support were not associated
      with decreased condom use. The path between substance use and decreased condom
      use approached significance. Results highlight the potential of prevention
      interventions that simultaneously boost self-efficacy and social support specific
      to practicing safer sex as well as those that reduce substance use.

PMID- 17014284
TI  - How does optimism suppress immunity? Evaluation of three affective pathways.
AB  - Studies have linked optimism to poorer immunity during difficult stressors. In
      this study, when 1st-year law students (N = 46) relocated to attend law school,
      reducing conflict among curricular and extracurricular goals, optimism predicted
      larger delayed-type hypersensitivity responses, indicating more robust in vivo
      cellular immunity. However, when students did not relocate, increasing goal
      conflict, optimism predicted smaller responses. Although this effect has been
      attributed to negative affect when difficult stressors violate optimistic
      expectancies, distress did not mediate optimism's effects on immunity.
      Alternative affective mediators related to engagement--engaged affect and fatigue
      -likewise failed to mediate optimism's effects, although all 3 types of affect
      independently influenced in vivo immunity. Alternative pathways include effort or
      self-regulatory depletion.

PMID- 17014285
TI  - Adolescent girls' and boys' weight-related health behaviors and cognitions:
      associations with reputation- and preference-based peer status.
AB  - In this study, the authors examined associations between preference- and
      reputation-based peer status and weight-related behaviors and cognitions for both
      adolescent boys and girls. Sociometric measures of peer like-ability and peer
      perceived popularity, as well as self-reported measures of body size, dieting
      behavior, and weight-related cognitions were collected from a sample of 441
      adolescents in Grades 11 and 12. Results revealed weight-related cognitions for
      girls (concerning obesity) and boys (concerning musculature/fitness). Peer
      perceived popularity, but not like-ability, was significantly associated with
      both boys' and girls' body size and dieting. Lower levels of popularity were
      associated with heavier body shapes for girls and with both thin and heavier body
      shapes for boys. Findings suggest that peer status is an important source of
      social reinforcement associated with weight-related behaviors and cognitions.

PMID- 17014286
TI  - Accuracy, error, and bias in predictions for real versus hypothetical events.
AB  - Participants made predictions about performance on tasks that they did or did not
      expect to complete. In three experiments, participants in task-unexpected
      conditions were unrealistically optimistic: They overestimated how well they
      would perform, often by a large margin, and their predictions were not correlated
      with their performance. By contrast, participants assigned to task-expected
      conditions made predictions that were not only less optimistic but strikingly
      accurate. Consistent with predictions from construal level theory, data from a
      fourth experiment suggest that it is the uncertainty associated with hypothetical
      tasks, and not a lack of cognitive processing, that frees people to make
      optimistic prediction errors. Unrealistic optimism, when it occurs, may be truly
      unrealistic; however, it may be less ubiquitous than has been previously
      suggested.

PMID- 17014287
TI  - Regulatory fit as input for stop rules.
AB  - Three experiments show that the motivational effects of regulatory fit
      (consistency between regulatory state and strategic means) are context dependent.
      With no explicit decision rule about when to stop (Experiment 1) or an explicit
      enjoyment stop rule (Experiments 2 and 3), participants exerted more effort on
      tasks when experiencing regulatory fit than when experiencing regulatory nonfit.
      With an explicit sufficiency stop rule (Experiments 2 and 3), participants
      exerted less effort when experiencing regulatory fit than when experiencing
      regulatory nonfit. The interactive effect of regulatory fit and stop rules can be
      explained by misattribution of rightness feelings from regulatory fit; the effect
      was eliminated by drawing participants' attention to an earlier event as a source
      of rightness feelings (Experiments 1 and 3).

PMID- 17014288
TI  - See what you want to see: motivational influences on visual perception.
AB  - People's motivational states--their wishes and preferences--influence their
      processing of visual stimuli. In 5 studies, participants shown an ambiguous
      figure (e.g., one that could be seen either as the letter B or the number 13)
      tended to report seeing the interpretation that assigned them to outcomes they
      favored. This finding was affirmed by unobtrusive and implicit measures of
      perception (e.g., eye tracking, lexical decision tasks) and by experimental
      procedures demonstrating that participants were aware only of the single (usually
      favored) interpretation they saw at the time they viewed the stimulus. These
      studies suggest that the impact of motivation on information processing extends
      down into preconscious processing of stimuli in the visual environment and thus
      guides what the visual system presents to conscious awareness.

PMID- 17014289
TI  - Jealousy and the threatened self: getting to the heart of the green-eyed monster.
AB  - Several theories specifying the causes of jealousy have been put forth in the
      past few decades. Firm support for any proposed theory, however, has been limited
      by the difficulties inherent in inducing jealousy and examining any proposed
      mediating mechanisms in real time. In support of a theory of jealousy centering
      on threats to the self-system, 2 experiments are presented that address these
      past limitations and argue for a model based on context-induced variability in
      self-evaluation. Experiment 1 presents a method for evoking jealousy through the
      use of highly orchestrated social encounters and demonstrates that threatened
      self-esteem functions as a principal mediator of jealousy. In addition to
      replicating these findings, Experiment 2 provides direct evidence for jealousy as
      a cause of aggression. The ability of the proposed theory of jealousy to
      integrate other extant findings in the literature is also discussed.

PMID- 17014290
TI  - Romantic involvement often reduces men's testosterone levels--but not always: the
      moderating role of extrapair sexual interest.
AB  - Testosterone (T) appears to facilitate what biologists refer to as mating effort-
      the investment of time and energy into same-sex competition and mate-seeking
      behavior. Multiple studies show that men who are romantically involved (i.e., are
      paired) have lower T than single men, which may be due to a facultative
      adjustment by men of T levels in response to lower demands for mating effort. The
      authors proceeded on the basis of the idea that men who retain interests in
      sexual opportunities with women other than a primary partner continue to dedicate
      more time and energy to mating effort when romantically paired, and so they
      predicted that the association between relationship status and T depends on men's
      extrapair sexual interests. Study 1 used the Sociosexual Orientation Inventory to
      measure extrapair sexual interests, whereas Study 2 used a broader measure to
      examine this interaction. Both studies found support for it. These results have
      implications for an understanding of the biosocial regulation of men's behavior
      in romantic relationships.

PMID- 17014291
TI  - Stereotyping and evaluation in implicit race bias: evidence for independent
      constructs and unique effects on behavior.
AB  - Implicit stereotyping and prejudice often appear as a single process in behavior,
      yet functional neuroanatomy suggests that they arise from fundamentally distinct
      substrates associated with semantic versus affective memory systems. On the basis
      of this research, the authors propose that implicit stereotyping reflects
      cognitive processes and should predict instrumental behaviors such as judgments
      and impression formation, whereas implicit evaluation reflects affective
      processes and should predict consummatory behaviors, such as interpersonal
      preferences and social distance. Study 1 showed the independence of participants'
      levels of implicit stereotyping and evaluation. Studies 2 and 3 showed the unique
      effects of implicit stereotyping and evaluation on self-reported and behavioral
      responses to African Americans using double-dissociation designs. Implications
      for construct validity, theory development, and research design are discussed.

PMID- 17014292
TI  - Regulation processes in intimate relationships: the role of ideal standards.
AB  - This research investigated the consistency between partner perceptions and ideal
      standards (ideal-perception consistency) and the partner regulation attempts of
      200 individuals involved in relationships (Study 1) and 62 heterosexual couples
      (Study 2). As predicted, greater regulation attempts were associated with lower
      ideal-perception consistency, and these links operated within 3 pivotal mate
      evaluation dimensions and were moderated by perceived regulation success. Ideal
      perception consistency also mediated the relation between partner regulation and
      relationship quality, and cross-lagged analyses suggested that ideal consistency
      and regulation influenced each other over time. Finally, stronger partner
      regulation was generally associated with more negative self-evaluations and more
      self-regulation by the targeted partner. These novel results support and extend
      the Ideal Standards Model (J. A. Simpson, G. J. O. Fletcher, & L. Campbell,
      2001).

PMID- 17014293
TI  - Procedural justice and the hedonic principle: how approach versus avoidance
      motivation influences the psychology of voice.
AB  - The authors investigate the relation between the hedonic principle (people's
      motivations to approach pleasure and to avoid pain) and procedural justice. They
      explore whether approach or avoidance motivation increases the effect that people
      feel they were treated more fairly following procedures that do versus do not
      allow them an opportunity to voice their opinion. Experiments 1 and 2 reveal that
      these procedures influence procedural justice judgments more strongly when people
      conduct approach motor action (arm flexion) than when they conduct avoidance
      motor action (arm extension). Experiment 3 indicates that individual-difference
      measures of participants' approach motivations predicted procedural justice
      judgments following voice versus no-voice procedures. The authors conclude that
      people's motivational orientations stimulate their fairness-based reactions to
      voice procedures.

PMID- 17014294
TI  - The paradox of group-based guilt: modes of national identification, conflict
      vehemence, and reactions to the in-group's moral violations.
AB  - The authors examined the relationships between 2 modes of national identification
      (attachment to the in-group and the in-group's glorification) and reactions to
      the in-group's moral violations among Israeli students. Data were collected
      during a period of relative calm in the Israeli-Palestinian conflict as well as
      during a period of great intensification of this conflict. As expected, in Study
      1, the 2 modes of identification had contrasting relationships with group-based
      guilt: Attachment was positively related whereas glorification was negatively
      related to group-based guilt for in-group's past infractions. Glorification
      suppressed the attachment effect but not vice versa. Both relationships were
      mediated by the use of exonerating cognitions. In Study 2, group-based guilt for
      the in-group's current wrongdoings was increased by priming critical rather than
      conventional attachment to the in-group, suggesting a causal effect of mode of
      identification on the experience of negative group-based emotions.

PMID- 17014295
TI  - Negotiation from a near and distant time perspective.
AB  - Across 3 experiments, the authors examined the effects of temporal distance on
      negotiation behavior. They found that greater temporal distance from negotiation
      decreased preference for piecemeal, single-issue consideration over integrative,
      multi-issue consideration (Experiment 1). They also found that greater temporal
      distance from an event being negotiated increased interest in conceding on the
      lowest priority issue and decreased interest in conceding on the highest priority
      issue (Experiment 2). Lastly, they found increased temporal distance from an
      event being negotiated produced a greater proportion of multi-issue offers, a
      greater likelihood of conceding on the lowest priority issue in exchange for a
      concession on the highest priority issue, and greater individual and joint
      outcomes (Experiment 3). Implications for conflict resolution and construal level
      theory are discussed.

PMID- 17014296
TI  - Psychological resilience, positive emotions, and successful adaptation to stress
      in later life.
AB  - In 3 studies, the authors investigated the functional role of psychological
      resilience and positive emotions in the stress process. Studies 1a and 1b
      explored naturally occurring daily stressors. Study 2 examined data from a sample
      of recently bereaved widows. Across studies, multilevel random coefficient
      modeling analyses revealed that the occurrence of daily positive emotions serves
      to moderate stress reactivity and mediate stress recovery. Findings also
      indicated that differences in psychological resilience accounted for meaningful
      variation in daily emotional responses to stress. Higher levels of trait
      resilience predicted a weaker association between positive and negative emotions,
      particularly on days characterized by heightened stress. Finally, findings
      indicated that over time, the experience of positive emotions functions to assist
      high-resilient individuals in their ability to recover effectively from daily
      stress. Implications for research into protective factors that serve to inhibit
      the scope, severity, and diffusion of daily stressors in later adulthood are
      discussed.

PMID- 17014297
TI  - The differential effects of intrinsic and identified motivation on well-being and
      performance: prospective, experimental, and implicit approaches to self
      determination theory.
AB  - Self-determination theory research has demonstrated that intrinsic and identified
      self-regulations are associated with successful adaptation. However, few
      distinctions are typically made between these regulations and their outcomes. In
      the present studies, the associations between intrinsic and identified
      motivations and outcomes of psychological well-being and academic performance are
      compared in educational settings. In Study 1, intrinsic self-regulation predicted
      psychological well-being, independent of academic performance. In contrast,
      identified regulation predicted academic performance. Additionally, the more that
      students demonstrated an identified academic regulation, the more that their
      psychological well-being was contingent on performance. In Study 2a, priming
      intrinsic self-regulation led to greater psychological well-being 10 days later.
      In Study 2b, an implicit measure of identified regulation predicted academic
      performance 6 weeks later. Results indicate the need to address important
      distinctions between intrinsic and identified regulations.

PMID- 17014298
TI  - A first large cohort study of personality trait stability over the 40 years
      between elementary school and midlife.
AB  - This report provides some initial findings from an investigation of the relations
      between childhood Big Five personality traits assessed by elementary school
      teachers and similar traits assessed 40 years later by self-reports at midlife (N
      = 799). Short-term (1-3 years) test-retest reliabilities were lower (.22-.53) in
      childhood when personality was developing than they were in adulthood (.70-.79)
      when personality stability should be at its peak. Stability coefficients across
      the 40-year interval between the childhood assessment and the 2 measures of
      adulthood personality were higher for Extraversion (e.g., .29) and
      Conscientiousness (e.g., .25) than for Openness (e.g., .16), Agreeableness (e.g.,
      .08), and Neuroticism (e.g., .00). Construct continuity between childhood and
      adulthood was evaluated by canonical analysis and by structural equation modeling
      and indicated continuity at both a broad, two-dimensional level and at the level
      of the Big Five. The findings are discussed in relation to A. Caspi, B. W.
      Roberts, and R. L. Shiner's (2005) principles of rank-order personality
      stability.

PMID- 17014299
TI  - Relating emotional abilities to social functioning: a comparison of self-report
      and performance measures of emotional intelligence.
AB  - Three studies used J. D. Mayer and P. Salovey's (1997) theory of emotional
      intelligence (EI) as a framework to examine the role of emotional abilities
      (assessed with both self-report and performance measures) in social functioning.
      Self-ratings were assessed in ways that mapped onto the Mayer-Salovey-Caruso
      Emotional Intelligence Test (MSCEIT), a validated performance measure of EI. In
      Study 1, self-ratings and MSCEIT scores were not strongly correlated. In Study 2,
      men's MSCEIT scores, but not self-ratings, correlated with perceived social
      competence after personality measures were held constant. In Study 3, only the
      MSCEIT predicted real-time social competence, again, just for men. Implications
      for analyzing how emotional abilities contribute to social behavior are
      discussed, as is the importance of incorporating gender into theoretical
      frameworks and study designs.

PMID- 17014300
TI  - Locally Bayesian learning with applications to retrospective revaluation and
      highlighting.
AB  - A scheme is described for locally Bayesian parameter updating in models
      structured as successions of component functions. The essential idea is to back
      propagate the target data to interior modules, such that an interior component's
      target is the input to the next component that maximizes the probability of the
      next component's target. Each layer then does locally Bayesian learning. The
      approach assumes online trial-by-trial learning. The resulting parameter updating
      is not globally Bayesian but can better capture human behavior. The approach is
      implemented for an associative learning model that first maps inputs to
      attentionally filtered inputs and then maps attentionally filtered inputs to
      outputs. The Bayesian updating allows the associative model to exhibit
      retrospective revaluation effects such as backward blocking and unovershadowing,
      which have been challenging for associative learning models. The back-propagation
      of target values to attention allows the model to show trial-order effects,
      including highlighting and differences in magnitude of forward and backward
      blocking, which have been challenging for Bayesian learning models.

PMID- 17014301
TI  - The physics of optimal decision making: a formal analysis of models of
      performance in two-alternative forced-choice tasks.
AB  - In this article, the authors consider optimal decision making in two-alternative
      forced-choice (TAFC) tasks. They begin by analyzing 6 models of TAFC decision
      making and show that all but one can be reduced to the drift diffusion model,
      implementing the statistically optimal algorithm (most accurate for a given speed
      or fastest for a given accuracy). They prove further that there is always an
      optimal trade-off between speed and accuracy that maximizes various reward
      functions, including reward rate (percentage of correct responses per unit time),
      as well as several other objective functions, including ones weighted for
      accuracy. They use these findings to address empirical data and make novel
      predictions about performance under optimality.

PMID- 17014302
TI  - Contextual guidance of eye movements and attention in real-world scenes: the role
      of global features in object search.
AB  - Many experiments have shown that the human visual system makes extensive use of
      contextual information for facilitating object search in natural scenes. However,
      the question of how to formally model contextual influences is still open. On the
      basis of a Bayesian framework, the authors present an original approach of
      attentional guidance by global scene context. The model comprises 2 parallel
      pathways; one pathway computes local features (saliency) and the other computes
      global (scene-centered) features. The contextual guidance model of attention
      combines bottom-up saliency, scene context, and top-down mechanisms at an early
      stage of visual processing and predicts the image regions likely to be fixated by
      human observers performing natural search tasks in real-world scenes.

PMID- 17014303
TI  - The extended argument dependency model: a neurocognitive approach to sentence
      comprehension across languages.
AB  - Real-time language comprehension is a principal cognitive ability and thereby
      relates to central properties of the human cognitive architecture. Yet how do the
      presumably universal cognitive and neural substrates of language processing
      relate to the astounding diversity of human languages (over 5,000)? The authors
      present a neurocognitive model of online comprehension, the extended argument
      dependency model (eADM), that accounts for cross-linguistic unity and diversity
      in the processing of core constituents (verbs and arguments). The eADM postulates
      that core constituent processing proceeds in three hierarchically organized
      phases: (1) constituent structure building without relational interpretation, (2)
      argument role assignment via a restricted set of cross-linguistically motivated
      information types (e.g., case, animacy), and (3) completion of argument
      interpretation using information from further domains (e.g., discourse context,
      plausibility). This basic architecture is assumed to be universal, with cross
      linguistic variation deriving primarily from the information types applied in
      Phase 2 of comprehension. This conception can derive the appearance of similar
      neurophysiological and neuroanatomical processing correlates in seemingly
      disparate structures in different languages and, conversely, of cross-linguistic
      differences in the processing of similar sentence structures.

PMID- 17014304
TI  - A hyper-emotion theory of psychological illnesses.
AB  - A hyper-emotion theory of psychological illnesses is presented. It postulates
      that these illnesses have an onset in which a cognitive evaluation initiates a
      sequence of unconscious transitions yielding a basic emotion. This emotion is
      appropriate for the situation but inappropriate in its intensity. Whenever it
      recurs, it leads individuals to a focus on the precipitating situation and to
      characteristic patterns of inference that can bolster the illness. Individuals
      with a propensity to psychological illness accordingly reason better than more
      robust individuals, but only on topics relevant to their illness. The theory is
      assessed in the light of previous research, a small epidemiological study of
      patients, and 3 empirical studies.

PMID- 17014305
TI  - A dynamical model of general intelligence: the positive manifold of intelligence
      by mutualism.
AB  - Scores on cognitive tasks used in intelligence tests correlate positively with
      each other, that is, they display a positive manifold of correlations. The
      positive manifold is often explained by positing a dominant latent variable, the
      g factor, associated with a single quantitative cognitive or biological process
      or capacity. In this article, a new explanation of the positive manifold based on
      a dynamical model is proposed, in which reciprocal causation or mutualism plays a
      central role. It is shown that the positive manifold emerges purely by positive
      beneficial interactions between cognitive processes during development. A single
      underlying g factor plays no role in the model. The model offers explanations of
      important findings in intelligence research, such as the hierarchical factor
      structure of intelligence, the low predictability of intelligence from early
      childhood performance, the integration/differentiation effect, the increase in
      heritability of g, and the Jensen effect, and is consistent with current
      explanations of the Flynn effect.

PMID- 17014306
TI  - An information search model of evaluative concerns in intergroup interaction.
AB  - In an information search model, evaluative concerns during intergroup interaction
      are conceptualized as a joint function of uncertainty regarding and importance
      attached to out-group members' views of oneself. High uncertainty generally
      fosters evaluative concerns during intergroup exchanges. Importance depends on
      whether out-group members' evaluations are perceived as diagnostic of one's
      social standing and outcomes. Perceived diagnosticity can arise from the out
      group's control over resources (contingency) and/or ability to provide accurate
      assessments (expertise) and is a function of the relative status of one's group
      and the perceived legitimacy of the group status difference. Evaluative concerns
      trigger information search efforts and forms of uncertainty reduction that have a
      variety of negative downstream effects. Implications for efforts to improve
      intergroup relations are discussed.

PMID- 17014307
TI  - Hierarchical schemas and goals in the control of sequential behavior.
AB  - Traditional accounts of sequential behavior assume that schemas and goals play a
      causal role in the control of behavior. In contrast, M. Botvinick and D. C. Plaut
      argued that, at least in routine behavior, schemas and goals are epiphenomenal.
      The authors evaluate the Botvinick and Plaut account by contrasting the simple
      recurrent network model of Botvinick and Plaut with their own more traditional
      hierarchically structured interactive activation model (R. P. Cooper & T.
      Shallice, 2000). The authors present a range of arguments and additional
      simulations that demonstrate theoretical and empirical difficulties for both
      Botvinick and Plaut's model and their theoretical position. The authors conclude
      that explicit hierarchically organized and causally efficacious schema and goal
      representations are required to provide an adequate account of the flexibility of
      sequential behavior.

PMID- 17014312
TI  - Use of a centrifugation-based, point-of-care device for production of canine
      autologous bone marrow and platelet concentrates.
AB  - OBJECTIVE: To analyze a centrifugation-based, point-of-care device that
      concentrates canine platelets and bone marrow-derived cells. ANIMALS: 19 adult
      sexually intact dogs. PROCEDURES: Anticoagulated peripheral blood (60 mL) and 60
      mL of anticoagulated bone marrow aspirate (BMA) were concentrated by
      centrifugation with the centrifugation-based, point-of-care device to form a
      platelet and a bone marrow concentrate (BMC) from 11 dogs. Blood samples were
      analyzed on the basis of hemograms, platelet count, and PCV. The BMA and BMC were
      analyzed to determine PCV, total nucleated cell count, RBC count, and
      differential cell counts. The BMC stromal cells were cultured in an
      osteoinductive medium. Eight additional dogs were used to compare the BMC yield
      with that in which heparin was infused into the bone marrow before aspiration.
      RESULTS: The centrifugation-based, point-of-care device concentrated platelets by
      6-fold over baseline (median recovery, 63.1%) with a median of 1,336 x 10(3)
      platelets/microL in the 7-mL concentrate. The nucleated cells in BMCs increased 7
      fold (median recovery, 42.9%) with a median of 720 x 10(3) cells/microL in the 4
      mL concentrate. The myeloid nucleated cells and mononuclear cells increased
      significantly in BMCs with a significant decrease in PCV, compared with that of
      BMAs. Stromal cell cultures expressed an osteoblastic phenotype in culture.
      Infusion of heparin into the bone marrow eliminated clot formation and created
      less variation in the yield (median recovery, 61.9%). CONCLUSIONS AND CLINICAL
      RELEVANCE: Bone marrow-derived cell and platelet-rich concentrates may form bone
      if delivered in an engineered graft, thus decreasing the need for cancellous bone
      grafts.

PMID- 17014313
TI  - Cytoarchitecture, morphology, and lumbosacral spinal cord projections of the red
      nucleus in cattle.
AB  - OBJECTIVE: To analyze the morphology, cytoarchitecture, and lumbosacral spinal
      cord projections of the red nucleus (RN) in cattle. ANIMALS: 8 healthy Friesian
      male calves. PROCEDURES: Anesthetized calves underwent a dorsal laminectomy at
      L5. Eight bilateral injections (lateral to the midline) of the neuronal
      retrograde fluorescent tracer fast blue (FB) were administered into the exposed
      lumbosacral portion of the spinal cord. A postsurgical calf survival time of 38
      to 55 days was used. Following euthanasia, the midbrain and the L5-S2 spinal cord
      segments were removed. Nissl's method of staining was applied on paraffin
      embedded and frozen sections of the midbrain. RESULTS: The mean length of the RN
      from the caudal to cranial end ranged from 6,680 to 8,640 microm. The
      magnocellular and parvicellular components of the RN were intermixed throughout
      the nucleus, but the former predominate at the caudal portion of the nucleus and
      the latter at the cranial portion with a gradual transitional zone. The FB
      labeled neurons were found along the entire craniocaudal extension of the
      nucleus, mainly in its ventrolateral part. The number of FB-labeled neurons was
      determined in 4 calves, ranging from 191 to 1,469 (mean, 465). The mean cross
      sectional area of the FB-labeled neurons was approximately 1,680 microm2.
      CONCLUSIONS AND CLINICAL RELEVANCE: In cattle, small, medium, and large RN
      neurons, located along the entire craniocaudal extension of the RN, contribute to
      the rubrospinal tract reaching the L6-S1 spinal cord segments. Thus, in cattle,
      as has been shown in cats, the RN parvicellular population also projects to the
      spinal cord.

PMID- 17014314
TI  - Pharmacokinetics of inhaled anesthetics in green iguanas (Iguana iguana).
AB  - OBJECTIVE: To test the hypothesis that differences in anesthetic uptake and
      elimination in iguanas would counter the pharmacokinetic effects of blood:gas
      solubility and thus serve to minimize kinetic differences among inhaled agents.
      ANIMALS: 6 green iguanas (Iguana iguana). PROCEDURES: Iguanas were anesthetized
      with isoflurane, sevoflurane, or desflurane in a Latin-square design. Intervals
      from initial administration of an anesthetic agent to specific induction events
      and from cessation of administration of an anesthetic agent to specific recovery
      events were recorded. End-expired gas concentrations were measured during
      anesthetic washout. RESULTS: Significant differences were not detected for any
      induction or recovery events for any inhalation agent in iguanas. Washout curves
      best fit a 2-compartment model, but slopes for both compartments did not differ
      significantly among the 3 anesthetics. CONCLUSIONS AND CLINICAL RELEVANCE:
      Differences in blood:gas solubility for isoflurane, sevoflurane, and desflurane
      did not significantly influence differences in pharmacokinetics for the
      inhalation agents in iguanas.

PMID- 17014315
TI  - Cardiopulmonary effects of buprenorphine in horses.
AB  - OBJECTIVE: To investigate the effects of buprenorphine on cardiopulmonary
      variables and on abdominal auscultation scores in horses. ANIMALS: 6 healthy
      adult horses. PROCEDURES: Horses were restrained in stocks and allocated to 2
      treatments in a randomized crossover design, with 1-week intervals between each
      treatment. Saline (0.9% NaCl) solution was administered IV as a control, whereas
      buprenorphine (10 mug/kg, IV) was administered to the experimental group.
      Cardiopulmonary data were collected for 120 minutes after buprenorphine or saline
      solution administration. Abdominal auscultation scores were monitored for 2 and
      12 hours after drug administration in the control and experimental groups,
      respectively. RESULTS: Following control treatment, horses remained calm while
      restrained in the stocks and no significant changes in cardiopulmonary variables
      were observed throughout the study. Buprenorphine administration caused
      excitatory phenomena (restlessness and head shaking). Heart rate, cardiac index,
      and arterial blood pressure were significantly increased after buprenorphine
      administration until the end of the observational period (120 minutes). Minimal
      changes were found in arterial blood gas tensions. Abdominal auscultation scores
      decreased significantly from baseline for 4 hours after buprenorphine
      administration. CONCLUSIONS AND CLINICAL RELEVANCE: Buprenorphine induced
      excitement and hemodynamic stimulation with minimal changes in arterial blood gas
      tensions. These effects may impact the clinical use of buprenorphine in horses.
      Further studies are indicated to investigate the effects of buprenorphine on
      gastrointestinal motility and fecal output.

PMID- 17014316
TI  - Pharmacokinetics of clarithromycin and concentrations in body fluids and
      bronchoalveolar cells of foals.
AB  - OBJECTIVE: To determine pharmacokinetics of clarithromycin and concentrations in
      body fluids and bronchoalveolar (BAL) cells of foals. ANIMALS: 6 healthy 2-to 3
      week-old foals. PROCEDURES: In a crossover design, clarithromycin (7.5 mg/kg) was
      administered to each foal via IV and intragastric (IG) routes. After the initial
      IG administration, 5 additional doses were administered IG at 12-hour intervals.
      Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in
      serum by use of high-performance liquid chromatography. A microbiologic assay was
      used to measure clarithromycin activity in serum, urine, peritoneal fluid,
      synovial fluid, CSF, pulmonary epithelial lining fluid (PELF), and BAL cells.
      RESULTS: After IV administration, elimination half-life (5.4 hours) and mean +/-
      SD body clearance (1.27 +/- 0.25 L/h/kg) and apparent volume of distribution at
      steady state (10.4 +/- 2.1 L/kg) were determined for clarithromycin. The
      metabolite was detected in all 6 foals by 1 hour after clarithromycin
      administration. Oral bioavailability of clarithromycin was 57.3 +/- 12.0%.
      Maximum serum concentration of clarithromycin after multiple IG administrations
      was 0.88 +/- 0.19 microg/mL. After IG administration of multiple doses,
      clarithromycin concentrations in peritoneal fluid, CSF, and synovial fluid were
      similar to or lower than concentrations in serum, whereas concentrations in
      urine, PELF, and BAL cells were significantly higher than concentrations in
      serum. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of clarithromycin
      at 7.5 mg/kg every 12 hours maintains concentrations in serum, PELF, and BAL
      cells that are higher than the minimum inhibitory concentration (0.12 microg/mL)
      for Rhodococcus equiisolates for the entire 12-hour dosing interval.

PMID- 17014317
TI  - Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin
      administered via regional intravenous limb perfusion in standing horses.
AB  - OBJECTIVE: To evaluate the pharmacokinetic-pharmacodynamic parameters of
      enrofloxacin and a low dose of amikacin administered via regional IV limb
      perfusion (RILP) in standing horses. ANIMALS: 14 adult horses. PROCEDURES:
      Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or
      amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb.
      Samples of interstitial fluid (collected via implanted capillary ultrafiltration
      devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying
      subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint
      were collected prior to (time 0) and at intervals after tourniquet release for
      determination of drug concentrations. For pharmacokinetic-pharmacodynamic
      analyses, minimum inhibitory concentrations (MICs) of 16 microg/mL (amikacin) and
      0.5 microg/mL (enrofloxacin) were applied. RESULTS: After RILP with enrofloxacin,
      3 horses developed vasculitis. The highest synovial fluid concentrations of
      enrofloxacin and amikacin were detected at time 0; median values (range) were
      13.22 microg/mL (0.254 to 167.9 microg/mL) and 26.2 microg/mL (5.78 to 50.0
      microg/mL), respectively. Enrofloxacin concentrations exceeded MIC for
      approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After
      perfusion of amikacin, concentrations greater than the MIC were not detected in
      any samples. Effective therapeutic concentrations of enrofloxacin were attained
      in all samples. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with orthopedic
      infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment
      option. However, care must be taken during administration. A dose of amikacin >
      250 mg is recommended to attain effective tissue concentrations via RILP in
      standing horses.

PMID- 17014318
TI  - Association between ceftiofur use and isolation of Escherichia coli with reduced
      susceptibility to ceftriaxone from fecal samples of dairy cows.
AB  - OBJECTIVE: To estimate the association between ceftiofur use and the isolation of
      Escherichia coli with reduced ceftriaxone susceptibility from fecal samples of
      dairy cow populations. ANIMALS: 1,266 dairy cows on 18 farms in Ohio. PROCEDURES:
      Individual fecal samples from all cows in the study herds were tested for
      Escherichia coli with reduced ceftriaxone susceptibility. Herd antimicrobial use
      policy and antimicrobial treatment records were also obtained. Plasmid DNA from
      these isolates was tested for the presence of the AmpC beta-lactamase gene
      (blaCMY-2). Minimum inhibitory concentrations to a standard panel of 16
      antimicrobial drugs were determined by use of a broth microdilution system.
      RESULTS: Herds for which ceftiofur use was reported were more likely to have cows
      from which reduced susceptibility E coli was isolated than herds that did not
      report ceftiofur use (odds ratio, 25.0). However, at the individual cow level, no
      association was found between recent ceftiofur treatment and isolation of reduced
      susceptibility E coli (adjusted odds ratio, 1.01). No observed linear
      relationship was found between the percentage of cows from which E coli with
      reduced ceftriaxone susceptibility was isolated and the percentage of cows in the
      herd recently treated with ceftiofur. CONCLUSIONS AND CLINICAL RELEVANCE: Our
      observation of a herd-level but not an individual cow-level association between
      ceftiofur use and isolation of E coli with reduced ceftriaxone susceptibility
      from fecal samples suggests that interventions to reduce the spread of
      antimicrobial resistance genes in agricultural animals will be most effective at
      the herd level.

PMID- 17014319
TI  - Evaluation of safety and pharmacokinetics of vancomycin after intraosseous
      regional limb perfusion and comparison of results with those obtained after
      intravenous regional limb perfusion in horses.
AB  - OBJECTIVE: To evaluate the clinical effects and pharmacokinetics of vancomycin in
      plasma and synovial fluid after intraosseous regional limb perfusion (IORLP) in
      horses and to compare results with those obtained after IV regional limb
      perfusion (IVRLP). ANIMALS: 6 horses. PROCEDURES: 1 forelimb of each horse
      received vancomycin hydrochloride (300 mg in 60 mL of saline [0.9% NaCl]
      solution) via IORLP; the contralateral limb received 60 mL of saline solution
      (control). Solutions were injected into the medullary cavity of the distal
      portion of the third metacarpal bone. Synovial fluid from the metacarpophalangeal
      (MTCP) and distal interphalangeal (DIP) joints and blood were collected prior to
      perfusion and 15, 30, 45, 65, and 90 minutes after beginning IORLP, and synovial
      fluid from the MTCP joint only and blood were collected 4, 8, 12, and 24 hours
      after beginning IORLP. Plasma urea and creatinine concentrations and clinical
      appearance of the MTCP joint region and infusion sites were determined daily for
      7 days. Results were compared with those of a separate IVRLP study. RESULTS:
      Clinical complications were not observed after IORLP. Mean vancomycin
      concentration in the MTCP joint was 4 microg/mL for 24 hours after IORLP.
      Compared with IORLP, higher vancomycin concentrations were detected in the DIP
      joint after IVRLP. Compared with IVRLP, higher vancomycin concentrations were
      detected in the MTCP joint for a longer duration after IORLP. CONCLUSIONS AND
      CLINICAL RELEVANCE: IORLP with 300 mg of vancomycin in a 0.5% solution was safe
      and may be clinically useful in horses. Intravenous and intraosseous routes may
      be better indicated for infectious processes in the DIP and MTCP joints,
      respectively.

PMID- 17014320
TI  - Effects of thermal energy on chondrocyte viability.
AB  - OBJECTIVE: To determine the critical temperature that reduces chondrocyte
      viability and evaluate the ability of chondrocytes to recover after exposure to
      the critical temperature. SAMPLE POPULATION: Cartilage explants obtained from the
      humeral heads of 30 sheep. PROCEDURES: In a randomized block design, 318 full
      thickness cartilage explants were collected from 30 humeral heads of sheep and
      cultured for up to 14 days. On the first day of culture (day 0), explants were
      subjected to temperatures of 37 degrees , 45 degrees , 50 degrees , 55 degrees ,
      60 degrees , or 65 degrees C for 5 minutes by heating culture tubes in a warming
      block. The ability for chondrocytes to recover after exposure to the critical
      temperature was determined by evaluating viability at days 0, 1, 3, 7, and 14
      days after heating. Images were analyzed by use of confocal laser microscopy.
      RESULTS: Analysis of images revealed a significant decrease in live cells and a
      significant increase in dead cells as temperature increased. Additionally, the
      deepest layer of cartilage had a significantly lower percentage of live cells,
      compared with values for the 3 most superficial layers. Chondrocytes did have
      some ability to recover temporarily after the initial thermal insult. CONCLUSIONS
      AND CLINICAL RELEVANCE: A strong relationship exists between increasing
      temperature and cell death, with a sharp increase in chondrocyte death between 50
      degrees and 55 degrees C. Chondrocytes in the deepest cartilage layer are most
      susceptible to thermal injury. The threshold of chondrocyte recovery from thermal
      injury is much lower than temperatures reached during chondroplasty by use of
      most radiofrequency energy devices.

PMID- 17014321
TI  - Assessment of collagen genes involved in fragmented medial coronoid process
      development in Labrador Retrievers as determined by affected sibling-pair
      analysis.
AB  - OBJECTIVE: To evaluate the involvement of various collagen genes in the
      development of fragmented medial coronoid process (FCP) in Labrador Retrievers.
      SAMPLE POPULATION: 93 dogs originating from 13 litters were used in the study;
      FCP was diagnosed in 35 dogs, and each affected dog had at least 1 sibling that
      was also affected. Twelve dams and sires were included in the analysis. All dogs
      were purebred Labrador Retrievers except for 2 litters (offspring of a female
      Golden Retriever-Labrador Retriever mixed-breed dog). PROCEDURES: For each dog,
      DNA was isolated from blood samples. Polymorphic microsatellite markers adjacent
      to 14 candidate genes (ie, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2,
      COL6A3, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, and COL24A1) were
      analyzed by use of PCR assays; genotypes were determined via automated detection
      of DNA products. The level of allele sharing between pairs of affected siblings
      was assessed. RESULTS: Among the 93 dogs, allele sharing of the 14 collagen genes
      was determined as follows: COL1A1, 45%; COL1A2, 47%; COL2A1, 37%; COL3A1, 32%;
      COL5A1, 43%; COL5A2, 32%; COL6A3, 36%; COL9A1, 45%; COL9A2, 49%; COL9A3, 38%;
      COL10A1, 46%; COL11A1, 52%; COL11A2, 47%; and COL24A1, 47%. CONCLUSIONS AND
      CLINICAL RELEVANCE: Because siblings share 50% of their genome at random, the
      fact that the percentages of allele sharing among the analyzed collagen genes
      were not significantly > 50% indicates that these genes are not determinant
      candidates for FCP in Labrador Retrievers. The gene for the vitamin D receptor
      could also be excluded because of its proximity to COL2A1.

PMID- 17014322
TI  - Histomorphometric analysis of articular cartilage, zone of calcified cartilage,
      and subchondral bone plate in femoral heads from clinically normal dogs and dogs
      with moderate or severe osteoarthritis.
AB  - OBJECTIVE: To quantify and compare the microscopic changes in articular cartilage
      (AC), zone of calcified cartilage (ZCC), and subchondral bone plate in femoral
      heads from clinically normal dogs and dogs with moderate or severe
      osteoarthritis. SAMPLE POPULATION: Femoral heads from clinically normal dogs (n =
      16) and dogs with moderate (24) or severe (14) osteoarthritis. PROCEDURES:
      Femoral heads were allocated to 3 categories (normal, moderate, or severe
      osteoarthritis) on the basis of radiographic findings, macroscopic findings, and
      histologic grade determined by use of a modified Mankin scale. Equally spaced 2
      mm sections were cut in each femoral head in a coronal or transverse plane.
      Thickness of the AC, ZCC, and subchondral bone plate was recorded. RESULTS: Mean
      thickness of AC was significantly greater in samples with moderate and severe
      osteoarthritis than those considered normal. Mean thickness of the ZCC was
      significantly greater in samples with moderate and severe osteoarthritis than
      those considered normal. Mean thickness of the subchondral bone plate in samples
      with severe osteoarthritis was significantly greater than those with moderate
      osteoarthritis and those considered normal. A significant decrease in AC
      thickness was detected in the proximomedial area of femoral heads with severe
      osteoarthritis, compared with those considered normal. CONCLUSIONS AND CLINICAL
      RELEVANCE: A cause and effect association between thickening of subchondral
      structures and thinning and loss of the overlying AC was not detected. Changes in
      AC were associated with changes in the subchondral bone plate, which is
      compatible with the theory of adaptation in response to altered load
      distribution.

PMID- 17014323
TI  - M-mode and Doppler echocardiographic reference values for male New Zealand white
      rabbits.
AB  - OBJECTIVE: To determine M-mode and Doppler echocardiographic reference values in
      healthy New Zealand white rabbits. ANIMALS: 52 healthy male rabbits. PROCEDURES:
      The rabbits were anesthetized and M-mode measurements of the left ventricle, left
      atrium, and aorta and Doppler measurements of pulmonary and aortic outflow and
      mitral inflow were recorded. RESULTS: Mean +/- SD heart rate during
      echocardiographic examination was 155 +/- 29 beats/min. Mean +/- SD measurements
      in diastole and systole for the interventricular septum thickness, left
      ventricular internal diameter, and left ventricular free wall thickness were 2.03
      +/- 0.37 mm and 3.05 +/- 0.45 mm; 14.37 +/- 1.49 mm and 10.25 +/- 1.22 mm; and
      2.16 +/- 0.25 and 3.48 +/- 0.55 mm, respectively. Mean +/- SD left atrial-to
      aortic diameter ratio was 1.17 +/- 0.14, and mean +/- SD mitral valve E-point-to
      septal separation interval was 1.71 +/- 0.29 mm. Mean +/- SD for fractional
      shortening and ejection fraction were 30.13 +/- 2.98% and 61.29 +/- 4.66%,
      respectively. Mean +/- SD maximal aortic and pulmonary artery outflow velocities
      were 0.85 +/- 0.11 m/s and 0.59 +/- 0.10 m/s, respectively, and the peak E-to
      peak A wave velocity ratio of the mitral valve was 2.19 +/- 0.46. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results provide echocardiographic reference values for young
      adult male New Zealand white rabbits anesthetized with ketamine and medetomidine.
      Values obtained from unanesthetized rabbits, rabbits sedated with other agents,
      or rabbits of different size may differ from those reported here.

PMID- 17014325
TI  - Concentrations of serum amyloid A in serum and synovial fluid from healthy horses
      and horses with joint disease.
AB  - OBJECTIVE: To determine serum amyloid A (SAA) concentrations in serum and
      synovial fluid from healthy horses and horses with joint disease and assess the
      effect of repeated arthrocentesis on SAA concentrations in synovial fluid.
      Animals-10 healthy horses and 21 horses with various types of joint disease.
      PROCEDURES: Serum and synovial fluid samples were obtained from each horse. In 5
      of the 10 healthy horses, arthrocentesis was repeated 9 times. Concentrations of
      SAA were determined via immunoturbidometry. RESULTS: Serum and synovial fluid SAA
      concentrations were less than the assay detection limit in healthy horses and did
      not change in response to repeated arthrocentesis. Synovial fluid SAA
      concentrations were significantly higher in horses with suspected bacterial joint
      contamination or infectious arthritis, or tenovaginitis than in healthy controls,
      and serum concentrations were significantly higher in horses with infectious
      conditions than in the other groups. Neither serum nor synovial fluid SAA
      concentrations in horses with low-inflammation joint conditions differed
      significantly from those in healthy controls. Concentrations of SAA and total
      protein in synovial fluid were significantly correlated. CONCLUSIONS AND CLINICAL
      RELEVANCE: Synovial fluid SAA concentration was a good marker of infectious
      arthritis and tenovaginitis and appeared to reflect changes in inflammatory
      activity. The advantages of use of SAA as a marker include the ease and speed of
      measurement and the fact that concentrations in synovial fluid were not
      influenced by repeated arthrocentesis in healthy horses. Further study of the SAA
      response in osteoarthritic joints to assess its usefulness in diagnosis and
      monitoring of osteoarthritis is warranted.

PMID- 17014326
TI  - Intraobserver and interobserver repeatability of ocular biometric measurements
      obtained by means of B-mode ultrasonography in dogs.
AB  - OBJECTIVE: To assess intra- and interobserver repeatability of ocular biometric
      measurements obtained by means of high-resolution B-mode ultrasonography in dogs.
      Animals-6 Beagles without ocular abnormalities. PROCEDURES: B-mode
      ultrasonography was performed bilaterally with a 10.5-MHz broadband compact
      linear array transducer. All measurements were made on 2 different occasions by 2
      observers. The Bland-Altman method was used to assess agreement between
      measurements obtained by the 2 observers and between the 2 sets of measurements
      obtained by each observer. RESULTS: Intra- and interobserver repeatability was
      highest for larger measurements, such as depth of the eye and depth of the
      anterior chamber. When repeatability was examined, bias was significantly
      different from 0 for only a few measurements, but the percentage difference
      between observations was as high as 180% for some measurements. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that most measurements of intraocular
      distances and structures obtained by means of high-resolution B-mode
      ultrasonography have acceptable intra- and interobserver repeatability. However,
      the percentage difference between observations can be high for smaller
      measurements.

PMID- 17014324
TI  - Effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function
      in anesthetized neonatal foals with induced hypotension.
AB  - OBJECTIVE: To determine the effects of dobutamine, norepinephrine, and
      vasopressin on cardiovascular function and gastric mucosal perfusion in
      anesthetized foals during isoflurane-induced hypotension. ANIMALS: 6 foals that
      were 1 to 5 days of age. PROCEDURES: 6 foals received 3 vasoactive drugs with at
      least 24 hours between treatments. Treatments consisted of dobutamine (4 and 8
      Sang/kg/min), norepinephrine (0.3 and 1.0 Sang/kg/min), and vasopressin (0.3 and
      1.0 mU/kg/min) administered IV. Foals were maintained at a steady hypotensive
      state induced by a deep level of isoflurane anesthesia for 30 minutes, and
      baseline cardiorespiratory variables were recorded. Vasoactive drugs were
      administered at the low infusion rate for 15 minutes, and cardiorespiratory
      variables were recorded. Drugs were then administered at the high infusion rate
      for 15 minutes, and cardiorespiratory variables were recorded a third time.
      Gastric mucosal perfusion was measured by tonometry at the same time points.
      RESULTS: Dobutamine and norepinephrine administration improved cardiac index.
      Vascular resistance was increased by norepinephrine and vasopressin
      administration but decreased by dobutamine at the high infusion rate. Blood
      pressure was increased by all treatments but was significantly higher during the
      high infusion rate of norepinephrine. Oxygen delivery was significantly increased
      by norepinephrine and dobutamine administration; O2 consumption decreased with
      dobutamine. The O2 extraction ratio was decreased following norepinephrine and
      dobutamine treatments. The gastric to arterial CO2 gap was significantly
      increased during administration of vasopressin at the high infusion rate.
      CONCLUSION AND CLINICAL RELEVANCE: Norepinephrine and dobutamine are better
      alternatives than vasopressin for restoring cardiovascular function and
      maintaining splanchnic circulation during isoflurane-induced hypotension in
      neonatal foals.

PMID- 17014327
TI  - Intraobserver and interobserver agreement, reproducibility, and accuracy of
      computed tomographic measurements of pituitary gland dimensions in healthy dogs.
AB  - OBJECTIVE: To determine the reproducibility and accuracy of computed tomographic
      (CT) measurements of pituitary gland dimensions in healthy dogs. ANIMALS: 35
      healthy sexually intact adult dogs. PROCEDURES: 2 observers independently viewed
      CT images of the skull in 35 dogs twice. Pituitary gland height, width, length,
      and volume and pituitary gland height-to-brain area ratio (P:B ratio) were
      measured or calculated. Intraobserver and interobserver agreement indexes (AIs)
      were calculated for pituitary gland dimensions. Computed tomography was performed
      also on 5 phantoms, and both observers measured phantom dimensions twice. True
      value AIs were calculated for the phantom study. RESULTS: The mean +/- SD
      interobserver AI between observer 1 and 2 for pituitary gland height and the P:B
      ratio was 0.90 +/- 0.07. The intraobserver AI for pituitary gland height and the
      P:B ratio was 0.97 +/- 0.04 for observer 1 and 0.94 +/- 0.04 for observer 2. The
      intra and interobserver AIs for the other dimensions were lower than those for
      pituitary gland height and the P:B ratio. All phantom dimensions on CT images
      were underestimated significantly, compared with their true values. CONCLUSIONS
      AND CLINICAL RELEVANCE: The intra- and interobserver AIs for pituitary gland
      dimension measurements on CT images were high. However, the same observer
      preferably should perform serial measurements. Window settings influence
      pituitary gland dimension measurements, and predetermined window settings are
      recommended to make comparisons among dogs. Pituitary gland dimension
      measurements made from CT images in our study underestimated the true values.

PMID- 17014328
TI  - Development of a fecal sample collection strategy for extraction and
      quantification of fecal immunoglobulin A in dogs.
AB  - OBJECTIVE: To develop a fecal sample collection strategy and quantification
      method for measurement of fecal IgA concentrations in dogs. SAMPLE POPULATION:
      Fecal samples from 23 healthy pet dogs of various breeds. PROCEDURES:
      Immunoglobulin A was extracted from fecal samples. An ELISA for the measurement
      of fecal IgA concentrations was established and analytically validated.
      Intraindividual variation of fecal IgA was determined by calculation of
      coefficients of variation. A sample collection strategy was developed on the
      basis of results of intraindividual variation of fecal IgA concentrations. A
      reference range for fecal IgA concentrations was determined. RESULTS: The method
      for extraction and quantification of fecal IgA was determined to be sufficiently
      sensitive, reproducible, accurate, and precise. On the basis of the
      intraindividual variability of our results, the determined fecal sample
      collection strategy required analysis of a total of 4 fecal samples/dog, with
      each fecal sample collected on 2 consecutive days with 28 days between sample
      collection periods (ie, days 1 and 2 followed by days 28 and 29). Reference range
      values for fecal IgA concentration were 0.22 to 3.24 mg/g of feces. CONCLUSIONS
      AND CLINICAL RELEVANCE: Methods of fecal IgA extraction and quantification used
      in our study allow for identification of dogs with consistently low fecal IgA
      concentrations. Use of these techniques will enable future investigations into
      possible associations between low fecal IgA concentrations and signs of
      gastrointestinal disease in dogs.

PMID- 17014329
TI  - Regulation by Jun N-terminal kinase/stress activated protein kinase of cytokine
      expression in Mycobacterium avium subsp paratuberculosis-infected bovine
      monocytes.
AB  - OBJECTIVE: To evaluate activation of Jun N-terminal kinase/stress-activated
      protein kinase (JNK/SAPK) pathway in bovine monocytes after incubation with
      Mycobacterium avium subsp paratuberculosis (Mptb) organisms. SAMPLE POPULATION:
      Bovine monocytes obtained from 4 healthy adult Holstein dairy cows. PROCEDURES:
      Bovine monocytes were incubated with Mptb organisms with or without a specific
      inhibitor of the JNK/SAPK pathway (SP600125) for 2, 6, 24, or 72 hours.
      Expression of interleukin (IL)-1beta, IL-10, IL-12, IL-18; transforming growth
      factor-beta (TGF-beta); and tumor necrosis factor-alpha (TNF-alpha) and the
      capacity of Mptb-infected monocytes to acidify phagosomes and kill Mptb organisms
      were evaluated. Phosphorylation status of JNK/SAPK was evaluated at 10, 30, and
      60 minutes after Mptb incubation. RESULTS: Compared with uninfected control
      monocytes, Mptb-infected monocytes had increased expression of IL-10 at 2 and 6
      hours after incubation and had increased expression of TNF-alpha, IL-1beta, IL
      18, and TGF-beta at 2, 4, and 6 hours. Additionally, Mptb-infected monocytes had
      increased expression of IL-12 at 6 and 24 hours. Addition of SP600125 (specific
      chemical inhibitor of JNK/SAPK) resulted in a decrease in TNF-alpha expression at
      2, 6, and 24 hours, compared with untreated Mptb-infected cells. Addition of
      SP600125 resulted in a decrease in TGF-beta expression at 24 hours and an
      increase in IL-18 expression at 6 hours. Addition of SP600125 failed to alter
      phagosome acidification but did enhance the capacity of monocytes to kill Mptb
      organisms. CONCLUSIONS AND CLINICAL RELEVANCE: Activation of JNK/SAPK may be an
      important mechanism used by Mptb to regulate cytokine expression in bovine
      monocytes for survival and to alter inflammatory and immune responses.

PMID- 17014330
TI  - Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline
      sarcoma.
AB  - OBJECTIVE: To determine somatic alterations in p53 in vaccine-associated feline
      sarcoma (VAFS). Animals-27 domestic shorthair cats undergoing first surgical
      treatment for primary VAFS with no history of chemotherapy or gamma radiation.
      PROCEDURES: Sequence analysis was performed on the genomic sequence of p53
      (between exons 5 through 9) from tumor and blood samples obtained from the cats.
      Cats were monitored for 3 years and disease-free intervals and survival times
      calculated. RESULTS: Eight single nucleotide polymorphisms were detected within
      the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at >
      or = 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in
      the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was
      significantly associated with rapid tumor recurrence and reduced overall
      survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The
      finding of malignant cells in the surgical margins was significantly associated
      with disease recurrence, but clear margins (with no detectable malignant cells)
      were not predictive of positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE: p53
      status is an indicator of postsurgical recurrence and overall survival in cats
      with VAFS. Careful follow-up is important in treating vaccine-site tumors
      containing allelic deletion of p53, whereas aggressive surgical treatment may be
      sufficient to control primary vaccination site tumors without the allelic loss.

PMID- 17014331
TI  - Evaluation of the anatomic effect of physical therapy exercises for mobilization
      of lumbar spinal nerves and the dura mater in dogs.
AB  - OBJECTIVE: To adapt and standardize neural tissue mobilization exercises,
      quantify nerve root movement, and assess the anatomic effects of lumbar spinal
      nerve and dural mobilization in dogs. ANIMALS: 15 canine cadavers. PROCEDURES: 5
      cadavers were used in the preliminary part of the study to adapt 3 neural tissue
      mobilization physical therapy exercises to canine anatomy. In the other 10
      cadavers, the L4 to L7 nerve roots and the dura at the level of T13 and L1 were
      isolated and marked. Movements during the physical therapy exercises were
      standardized by means of goniometric control. Movement of the nerve roots in
      response to each exercise was digitally measured. The effects of body weight and
      crownrump length on the distance of nerve root movement achieved during each
      exercise were also assessed. Each exercise was divided into 4 steps, and the
      overall distance of neural movement achieved was compared with distances achieved
      between steps. RESULTS: Neural tissue mobilization exercises elicited visible and
      measurable movement of nerve roots L4 to L7 and of the dura at T13 and L1 in all
      cadavers. CONCLUSIONS AND CLINICAL RELEVANCE: The physical therapy exercises
      evaluated had measurable effects on nerve roots L4 to L7 and the dura mater in
      the T13 and L1 segments. These exercises should be evaluated in clinical trials
      to validate their efficacy as primary treatments or ancillary postsurgical
      therapy in dogs with disorders of the thoracolumbar and lumbosacral segments of
      the vertebral column.

PMID- 17014333
TI  - Duration of corneal anesthesia following topical administration of 0.5%
      proparacaine hydrochloride solution in clinically normal cats.
AB  - OBJECTIVE: To determine duration of corneal anesthesia following topical
      administration of 0.5% proparacaine hydrochloride solution in domestic shorthair
      (DSH) cats. ANIMALS: 20 clinically normal DSH cats. PROCEDURES: Baseline corneal
      touch threshold (CCT) was established by use of a Cochet-Bonnet aesthesiometer.
      Treatment consisted of a single 50-microL topical application of an ophthalmic
      preparation of 0.5% proparacaine solution to a randomly selected eye of each cat.
      The corneal touch threshold was assessed 1 and 5 minutes after application to the
      cornea and at 5- minute intervals thereafter for 60 minutes. RESULTS: Corneal
      sensitivity, as determined by Cochet-Bonnet aesthesiometry, was significantly
      reduced from baseline for 25 minutes following topical administration of
      ophthalmic proparacaine. Maximal anesthetic effect lasted 5 minutes. CONCLUSIONS
      AND CLINICAL RELEVANCE: As determined by Cochet-Bonnet aesthesiometry, duration
      of anesthetic effects on the cornea induced by a single topical application of an
      ophthalmic preparation of 0.5% proparacaine solution in DSH cats is considerably
      shorter than the reported duration of corneal anesthesia in dogs.

PMID- 17014334
TI  - Effects of topical administration of an aldose reductase inhibitor on cataract
      formation in dogs fed a diet high in galactose.
AB  - OBJECTIVE: To determine effects of a topical formulation of an aldose reductase
      inhibitor (ARI) on the development of sugar cataracts in dogs fed a diet high in
      galactose. Animals-Ten 6-month old Beagles. PROCEDURES: Dogs were fed a diet
      containing 30% galactose, and after 16 weeks, 6 dogs were treated topically with
      a proprietary ARI formulation and 4 dogs were treated with a placebo. Cataract
      formation was monitored by means of slit-lamp biomicroscopy and fundus
      photography. Dogs were euthanized after 10 weeks of treatment, and lenses were
      evaluated for degree of opacity, myo-inositol and galactitol concentrations, and
      concentration of the ARI. RESULTS: All dogs developed bilateral cortical
      opacities dense enough to result in a decrease in the tapetal reflex after being
      fed the galactose-containing diet for 16 weeks. Administration of the ARI
      arrested further development of cataract formation. In contrast, cataracts in the
      vehicle-treated dogs progressed over the 10-week period to the mature stage.
      Evaluation of the isolated lenses after 26 weeks of galactose feeding indicated
      that lenses from treated dogs were significantly less optically dense than lenses
      from control dogs. Lenticular myo-inositol concentration was significantly higher
      in the treated than in the control dogs. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that topical application of a proprietary ARI formulation may
      arrest or reverse the development of sugar cataracts in dogs fed a diet high in
      galactose. This suggests that this ARI formulation may be beneficial in
      maintaining or improving functional vision in diabetic dogs with early lens
      opacities.

PMID- 17014335
TI  - In vitro fungistatic and fungicidal activities of silver sulfadiazine and
      natamycin on pathogenic fungi isolated from horses with keratomycosis.
AB  - OBJECTIVE: To evaluate the in vitro antifungal properties of silver sulfadiazine
      (SSD) and natamycin against filamentous fungi isolated from eyes of horses with
      keratomycosis. SAMPLE POPULATION: Filamentous fungal isolates obtained from eyes
      of keratomycosis-affected horses. PROCEDURES: Fungal culture of ocular samples
      yielded 6 Fusarium spp; 7 Aspergillus spp; and 1 isolate each of Curvularia,
      Scopulariopsis, Penicillium, and Chrysosporium. For each fungal isolate, minimum
      inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of SSD
      and natamycin were determined. RESULTS: For all 17 fungal isolates, SSD MIC
      distribution ranged from < or = 1 to > 64 microg/mL; MIC50 and MIC90 (MICs at
      which 50% and 90% of organisms were inhibited) were 4 and 32 microg/mL,
      respectively. The SSD MFC distribution for all isolates was < or = 1 to > 64
      microg/mL; MFC50 and MFC90 (MFCs at which 50% and 90% of organisms were killed)
      were 8 and > 64 microg/mL, respectively. For all fungal isolates, natamycin MIC
      distribution ranged from 256 to > 1,000 microg/mL; MIC50 and MIC90 were 512 and >
      1,000 microg/mL, respectively. The natamycin MFC distribution for all isolates
      ranged from 512 to > 1,000 microg/mL; MFC(50) and MFC(90) were each > 1,000
      microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: These in vitro data suggest that
      SSD is fungicidal against the fungal isolates that were obtained from eyes of
      horses with keratomycosis and that natamycin is fungicidal against some of the
      isolates at the drug concentrations evaluated. Silver sulfadiazine may be a
      therapeutic option for equine keratomycosis.

PMID- 17014337
TI  - Parenteral vaccination of domestic pigs with Brucella abortus strain RB51.
AB  - OBJECTIVE: To determine the immunogenicity and efficacy of Brucella abortus
      strain RB51 (SRB51) as a vaccine in domestic pigs. ANIMALS: Sixty-eight 6-week
      old crossbred domestic pigs and twenty-four 4-month-old gilts. PROCEDURES: In
      experiment 1, pigs were vaccinated IM (n = 51) with 2 x 10(10) CFUs of SRB51 or
      sham inoculated (17). Periodic blood samples were obtained to perform blood
      cultures, serologic evaluations, and cell-mediated immunity assays. Necropsies
      were performed at selected times between weeks 1 and 23 after vaccination to
      determine vaccine clearance. In experiment 2, gilts were similarly vaccinated (n
      = 18) or sham inoculated (8) and similar samples were obtained after vaccination.
      Gilts were bred and challenged conjunctivally with 5.0 x 10(7) CFUs of virulent
      Brucella suis strain 3B. Necropsies were performed on gilts and on fetuses or
      neonates after abortion or parturition, respectively. Bacterial cultures and
      serologic evaluations were performed on samples obtained at necropsy to determine
      vaccine efficacy. RESULTS: Humoral and cell-mediated immune responses did not
      differ between vaccinates and controls. After vaccination, SRB51 was not isolated
      from blood cultures of either group and was isolated from lymphoid tissues of 3
      pigs at 2 weeks (n = 2) and 4 weeks (1) after vaccination. No differences were
      found in isolation of B suis or in seroconversion between vaccinated and control
      gilts and between their neonates or aborted fetuses. CONCLUSIONS AND CLINICAL
      RELEVANCE: Parenteral vaccination with SRB51 does not induce humoral or cell
      mediated immune responses. Vaccination with SRB51 did not protect gilts or their
      neonates and fetuses from virulent challenge with B suis.

PMID- 17014336
TI  - Effect of short-term sequential administration of nonsteroidal anti-inflammatory
      drugs on the stomach and proximal portion of the duodenum in healthy dogs.
AB  - OBJECTIVE: To evaluate effects of injection with a nonsteroidal anti-inflammatory
      drug (NSAID) followed by oral administration of an NSAID on the gastrointestinal
      tract (GIT) of healthy dogs. ANIMALS: 6 healthy Walker Hounds. PROCEDURES: In a
      randomized, crossover design, dogs were administered 4 treatments consisting of
      an SC injection of an NSAID or control solution (day 0), followed by oral
      administration of an NSAID or inert substance for 4 days (days 1 through 4).
      Treatment regimens included carprofen (4 mg/kg) followed by inert substance;
      saline (0.9% NaCl) solution followed by deracoxib (4 mg/kg); carprofen (4 mg/kg)
      followed by carprofen (4 mg/kg); and carprofen (4 mg/kg) followed by deracoxib (4
      mg/kg). Hematologic, serum biochemical, and fecal evaluations were conducted
      weekly, and clinical scores were obtained daily. Endoscopy of the GIT was
      performed before and on days 1, 2, and 5 for each treatment. Lesions were scored
      by use of a 6-point scale. RESULTS: No significant differences existed for
      clinical data, clinicopathologic data, or lesion scores in the esophagus, cardia,
      or duodenum. For the gastric fundus, antrum, and lesser curvature, an effect of
      time was observed for all treatments, with lesions worsening from before to day 2
      of treatments but improving by day 5. CONCLUSIONS AND CLINICAL RELEVANCE:
      Sequential administration of NSAIDs in this experiment did not result in
      clinically important gastroduodenal ulcers. A larger study to investigate the
      effect of sequential administration of NSAIDs for longer durations and in dogs
      with signs of acute and chronic pain is essential to substantiate these findings.

PMID- 17014339
TI  - Psychiatry and psychoanalysis in Iran.

PMID- 17014340
TI  - A conceptual model of transference and its psychotherapeutic application.
AB  - The tendency to repeat formative human relationships in later life, a universal
      developmental characteristic, is referred to as transference when it occurs in
      the doctor-patient relationship. Its systematic therapeutic application in
      psychiatry has historically been associated with classical psychoanalysis. As
      psychoanalysis has lost its cachet, and as drug treatment has replaced
      psychotherapy as psychiatry's major treatment modality, the therapeutic potential
      of transference risks being neglected. This is to the great detriment of
      psychiatric patients. Knowledge of the power of transference and expertise in its
      clinical use in psychotherapy should be the most powerful tool in the psychiatric
      therapeutic armamentarium. This article discusses a concept of transference that
      the author has found effective, both in clinical practice and in teaching about
      transference to psychiatric residents. The article delineates a psychology of
      transference, discusses its universal applicability to the whole of the
      psychotherapeutic process, and utilizes case material to illustrate principles of
      its application.

PMID- 17014341
TI  - A view from Riggs: introduction to paper II "Treatment resistance and patient
      authority".

PMID- 17014342
TI  - A view from Riggs: treatment resistance and patient authority-II. Transmission of
      trauma and treatment resistance.
AB  - Treatment resistance has emerged as a significant issue in our era emphasizing
      biological treatments for psychiatric disorders. This article suggests that some
      patients who carry trauma from previous generations become treatment resistant
      because of this burden. Advancing the treatment of these patients often requires
      openness to the burdens of past generations and attention to unraveling their
      meaning.

PMID- 17014343
TI  - The unconscious and the creative process.
AB  - Both psychologist and writer, the author describes the creative process from
      research, psychological, psychoanalytic, and personal experiential perspectives.
      The approaches of Ernest Hemingway, Stephen King, and W. Somerset Maugham to
      their work are very different, illustrating that the expression of creativity is
      idiosyncratic and unique. Examples of the author's creative process are also
      presented. Creativity can be used to help the writer come to terms with and to
      master his or her conflicts as described by Ray Bradbury. It can also be used
      simply to discharge those conflicts without coming to terms with them as was the
      work of Sylvia Plath. The relation between dreaming and creativity is discussed.
      Creativity is viewed not only as a vehicle for self-expression but also as a
      vehicle for self-discovery. The therapist's creativity and its relevance to the
      treatment process is also pointed out.

PMID- 17014344
TI  - Psychodynamic psychiatry--past, present, and future.
AB  - At this point in the history of psychiatry it is important for psychodynamic
      psychiatry to strengthen its identity as a discipline in its own right-distinct
      from organized psychoanalysis. Although some of its principles overlap with
      psychoanalytic psychology, there are important differences. Psychodynamic
      psychiatry places a greater emphasis on immediate therapeutic outcome. It has a
      much wider patient base, and flexible models of duration and frequency of
      treatment. Its assumptions also rest on scientifically validated data to a much
      larger degree than psychoanalysis. A sturdier identity might help psychodynamic
      psychiatry stand alongside bio-descriptive psychiatry as a core component of
      American Psychiatry.

PMID- 17014345
TI  - Questions of technique following the psychoanalytic perspective of Erich Fromm.
AB  - To avoid dogma and ritual Erich Fromm chose not to write a book on psychoanalytic
      technique, leaving his teachings to the oral tradition of his pupils which
      advises us to treat each patient and each session as unique. The rules of
      technique are neither revoked nor denied but rather discussed and criticized. In
      the author's opinion the "question of technique" takes the place of technique,
      making the Frommian approach wholly current and in dialogue with interpersonal
      and relational orientations in psychoanalysis. On this dialectical line and
      assuming the analyst's awareness as point of view, the theme of the relationship
      between the here-and-now of the session and the there-and-then of the analysand's
      life is developed. A dialectical context is also offered between operations of
      objectivization and operations of alienation in the psychoanalytic process.

PMID- 17014346
TI  - On Perseus.
AB  - The story of Perseus and his exploits is one of the most famous Greek myths and
      is analyzed with emphasis on oedipal and symbiotic dynamics. The myth is seen to
      resonate with individual, social, and historical elements, illustrating the
      unique place of symbol and myth in mediating the coevolution of the individual
      and his or her culture.

PMID- 17014347
TI  - Suicide bombing: a psychodynamic view.
AB  - The horror and macabre images of suicide bombings appear regularly on television
      news programs around the world. A focused literature review of psychiatric
      interview and demographic data about suicide bombers is presented. Of particular
      clinical interest are the findings from the study of potential suicide bombers
      who were apprehended before they could act on their suicide bombing plans. The
      authors offer psychodynamic and social self-psychological theories explaining the
      phenomenon of suicide bombing behavior.

PMID- 17014351
TI  - Commentary on animal rights stirs more debate.

PMID- 17014352
TI  - What is your diagnosis? Cranial mediastinal soft tissue mass.

PMID- 17014353
TI  - What is your diagnosis? Multiple cartilaginous exostoses.

PMID- 17014354
TI  - Employment, starting salaries, and educational indebtedness of year-2006
      graduates of US veterinary medical colleges.

PMID- 17014355
TI  - Evaluation of ProMED-mail as an electronic early warning system for emerging
      animal diseases: 1996 to 2004.
AB  - OBJECTIVE: To identify emerging animal and zoonotic diseases and associated
      geographic distribution, disease agents, animal hosts, and seasonality of
      reporting in the Program for Monitoring Emerging Diseases (ProMED)-mail
      electronic early warning system. DESIGN: Retrospective study. SAMPLE POPULATION:
      10,490 disease reports. PROCEDURES: Descriptive statistics were collated for all
      animal disease reports appearing on the ProMED-mail system from January 1, 1996,
      to December 31, 2004. RESULTS: Approximately 30% of reports concerned events in
      the United States; reports were next most common in the United Kingdom, Canada,
      Australia, Russia, and China. Rabies, bovine spongiform encephalopathy, and
      anthrax were reported consistently over the study period, whereas avian
      influenza, Ebola virus, and Hantavirus infection were reported frequently in
      approximately half of the study years. Reports concerning viral agents composed
      more than half of the postings. Humans affected by zoonotic disease accounted for
      a third of the subjects. Cattle were affected in 1,080 reports, and wildlife
      species were affected in 825 reports. For the 10,490 postings studied, there was
      a retraction rate of 0.01 and a correction rate of 0.02. CONCLUSIONS AND CLINICAL
      RELEVANCE: ProMED-mail provided global coverage, but gaps in coverage for
      individual countries were detected. The value of a global electronic reporting
      system for monitoring emerging diseases over a 9-year period illustrated how new
      technologies can augment disease surveillance strategies. The number of animal
      and zoonotic diseases highlights the importance of animals in the study of
      emerging diseases.

PMID- 17014356
TI  - Summary of adverse event reports for veterinary biologic products received by the
      USDA from 1999 through 2005.

PMID- 17014357
TI  - Evaluation of epidural administration of morphine or morphine and bupivacaine for
      postoperative analgesia after premedication with an opioid analgesic and
      orthopedic surgery in dogs.
AB  - OBJECTIVE: To evaluate the analgesic efficacy of epidural administration of
      morphine or a morphine-bupivacaine combination administered before orthopedic
      surgery in dogs that received opioid premedication. DESIGN: Prospective,
      randomized, blinded, clinical study. ANIMALS: 36 healthy adult dogs that
      underwent elective orthopedic surgery on a pelvic limb. PROCEDURES: Each dog
      received 1 of 3 epidural treatments before surgery. Anesthetic and supportive
      care protocols were standardized. Dogs under going different surgical procedures
      were randomly allocated among the 3 treatment groups. Respiratory and
      cardiovascular variables, end-tidal isoflurane concentration, and requirements
      for rescue analgesia were monitored. Postsurgical analgesia was evaluated with a
      multiparametric pain scoring system and by determination of rescue analgesia
      requirements and cortisolemia. RESULTS: The morphine-bupivacaine combination was
      associated with lower values than morphine or a saline solution for
      intraoperative arterial blood pressure; minimum and maximum isoflurane
      requirements; and postoperative pain scores, rescue analgesia requirements, and
      plasma cortisol concentrations. Values obtained after administration of morphine
      alone were not significantly different from those obtained after administration
      of saline solution for most variables. CONCLUSIONS AND CLINICAL RELEVANCE: The
      preoperative epidurally administered morphine-bupivacaine combination induced
      better analgesia than morphine alone and should be considered for use in clinical
      patients. The degree of hemodynamic depression associated with the combination
      was considered acceptable for healthy patients undergoing elective surgery.

PMID- 17014359
TI  - Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight
      dogs.
AB  - CASE DESCRIPTION: 8 adult dogs were evaluated for treatment of lethargy and
      vomiting after ingestion of xylitol, a sugar alcohol used as a sweetener in
      various products. CLINICAL FINDINGS: In addition to vomiting and lethargy, 5 of
      the dogs had widespread petechial, ecchymotic, or gastrointestinal tract
      hemorrhages. Common clinicopathologic findings included moderately to severely
      high serum activities of liver enzymes, hyperbilirubinemia, hypoglycemia,
      hyperphosphatemia, prolonged clotting times, and thrombocytopenia. Necropsies
      were performed on 3 dogs and severe hepatic necrosis was found in 2. In the third
      dog, histologic examination revealed severe hepatocyte loss or atrophy with
      lobular collapse. TREATMENT AND OUTCOME: Treatments varied among dogs and
      included IV administration of fluids; plasma transfusions; and, if indicated,
      administration of dextrose. Three dogs were euthanatized, 2 dogs died, 2 dogs
      made a complete recovery, and 1 dog was recovering but was lost to follow-up.
      CLINICAL RELEVANCE: Although xylitol causes hypoglycemia in dogs, hepatic failure
      after ingestion has not previously been reported. Because an increasing number of
      consumer products contain xylitol, clinicians should be aware that ingestion of
      xylitol can have serious, life-threatening effects.

PMID- 17014360
TI  - Spontaneous retrograde movement of ureteroliths in two dogs and five cats.
AB  - CASE DESCRIPTION: 2 dogs and 5 cats were evaluated for treatment of ureteroliths.
      CLINICAL FINDINGS: Spontaneous retrograde movement of 1 or more ureteroliths was
      detected by radiography, ultrasonography, fluoroscopy, and a combination of
      fluoroscopy and ultrasonography. The ureteroliths moved retrograde up to 4
      centimeters. Retrograde movement of ureteroliths into the renal pelvis resulted
      in improved renal function in some patients but made complete surgical removal of
      all uroliths more difficult. TREATMENT AND OUTCOME: Medical management was not
      successful, and ureteroliths were surgically removed. Surgical management of
      ureteroliths was complicated by retrograde movement of ureteroliths in the
      perioperative period. CLINICAL RELEVANCE: Ureteroliths can move retrograde within
      the ureter and even back into the renal pelvis. Retrograde movement of
      ureteroliths may make surgical planning more difficult.

PMID- 17014361
TI  - Association of portovenographic findings with outcome in dogs receiving surgical
      treatment for single congenital portosystemic shunts: 45 cases (2000-2004).
AB  - OBJECTIVE: To determine whether hepatic portal vascularity, as assessed by
      intraoperative mesenteric portovenography (IMP), is related to outcome in dogs
      undergoing attenuation of single congenital portosystemic shunts (CPSSs). DESIGN:
      Retrospective case series. ANIMALS: 45 dogs, each with a single CPSS, in which
      IMP was performed before and after temporary complete occlusion of the shunting
      vessel and that underwent complete (17 dogs) or partial (28 dogs) CPSS
      attenuation (surgery 1). PROCEDURES: Medical records were reviewed for
      signalment, clinical history, and bile acids stimulation test results.
      Intrahepatic portal vessel (IPV) opacification in pre- and postocclusion
      portovenograms was graded to determine whether the degree of opacification was
      correlated with the degree of shunt attenuation, clinical or biochemical factors,
      or long-term clinical outcome. In 17 of 28 dogs that had partial CPSS
      attenuation, these procedures were subsequently repeated (surgery 2) to achieve
      complete (14 dogs) or further partial (3 dogs) CPSS attenuation. RESULTS:
      Compared with preattenuation findings, IPV opacification increased significantly
      after partial or complete CPSS attenuation. The degree of IPV opacification
      before and after CPSS occlusion (surgery 1) was greater in dogs that tolerated
      complete versus partial CPSS attenuation and was correlated positively with age.
      The degree of IPV opacification following CPSS occlusion (surgery 1) was maximal
      in all dogs without encephalopathy and was correlated negatively with follow-up
      preprandial serum bile acids concentrations and positively with clinical
      improvement. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that IMP can be
      used to assess changes in IPV blood flow and help predict outcome following
      attenuation of single CPSSs in dogs.

PMID- 17014362
TI  - Diagnostic value of cytologic examination of gastrointestinal tract tumors in
      dogs and cats: 83 cases (2001-2004).
AB  - OBJECTIVE: To determine results of cytologic examination of fine-needle aspirates
      and impression smears of gastrointestinal tract tumors in dogs and cats. DESIGN:
      Retrospective case series. ANIMALS: 38 dogs and 44 cats with histologically
      confirmed gastrointestinal tract tumors. PROCEDURES: Results of cytologic
      examination of fine-needle aspirates (n = 67) or impression smears (31) were
      compared with the histologic diagnosis, and extent of agreement was classified as
      complete, partial, none, or undetermined. RESULTS: For 48 of the 67 (72%) fine
      needle aspirates, there was complete or partial agreement between the cytologic
      and histologic diagnoses. For 12 (18%) aspirates, the extent of agreement could
      not be determined because the cytologic specimen was considered unsatisfactory.
      For 29 of the 31 (94%) impression smears, there was complete agreement between
      the cytologic and histologic diagnoses, and for 2 (6%), there was partial
      agreement. None of the impression smears were considered unsatisfactory.
      Proportion of samples with complete agreement and proportion of samples with
      complete or partial agreement were significantly higher for impression smears
      than for fine-needle aspirates. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that there was moderate agreement between results of cytologic
      examination of fine-needle aspirates from dogs and cats with gastrointestinal
      tract neoplasia and the definitive histologic diagnosis. The agreement between
      results of cytologic examination of impression smears and the histologic
      diagnosis appeared to be higher.

PMID- 17014363
TI  - Seasonal pasture myopathy in horses in the midwestern United States: 14 cases
      (1998-2005).
AB  - OBJECTIVE: To determine clinical signs, diagnostic findings, tissue tremetone
      concentrations, and clinical outcome or postmortem findings in horses evaluated
      for acute severe nonexertional rhabdomyolysis initially attributed to white
      snakeroot toxicosis. DESIGN: Retrospective case series. ANIMALS: 14 horses.
      PROCEDURES: Records of the University of Minnesota Veterinary Medical Center or
      Diagnostic Laboratory were searched from 1998 to 2005. Inclusion criteria
      included serum creatine kinase (CK) activity > 45,000 U/L, severe nonexertional
      myonecrosis of proximal postural muscles at necropsy, or signs of weakness
      without palpably firm muscles on physical examination. Vitamin E and selenium
      concentrations were measured in 6 horses; tremetone concentration was measured in
      7. RESULTS: Clinical signs occurred during unfavorable weather conditions.
      Clinical signs of generalized weakness (n = 11 horses), muscle fasciculations
      (10), lethargy (6), and prolonged recumbency (4) were common. Serum CK activity
      ranged from 46,487 to 959,499 U/L (reference range, 82 to 449 U/L), and aspartate
      transaminase activity was > 1,500 U/L (reference range, 162 to 316 U/L). Two
      horses survived with aggressive antioxidant and fluid treatment. Postmortem
      examination revealed acute severe myonecrosis with lipid accumulation primarily
      in neck, proximal forelimb and hind limb, intercostal, and diaphragm muscles.
      Histopathologic signs of myocardial necrosis were detected in 7 horses. Vitamin E
      and selenium concentrations were within reference limits. Tremetone was not
      detected in liver or urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Cases of
      rhabdomyolysis have been attributed to white snakeroot toxicosis; however,
      tremetone was not detected in any horses. Similarities exist between cases of
      seasonal pasture myopathy and cases of atypical myopathy in Europe.

PMID- 17014364
TI  - Targeting antioxidants to mitochondria by conjugation to lipophilic cations.
AB  - Mitochondrial oxidative damage contributes to a range of degenerative diseases.
      Consequently, the selective inhibition of mitochondrial oxidative damage is a
      promising therapeutic strategy. One way to do this is to invent antioxidants that
      are selectively accumulated into mitochondria within patients. Such mitochondria
      targeted antioxidants have been developed by conjugating the lipophilic
      triphenylphosphonium cation to an antioxidant moiety, such as ubiquinol or alpha
      tocopherol. These compounds pass easily through all biological membranes,
      including the blood-brain barrier, and into muscle cells and thus reach those
      tissues most affected by mitochondrial oxidative damage. Furthermore, because of
      their positive charge they are accumulated several-hundredfold within
      mitochondria driven by the membrane potential, enhancing the protection of
      mitochondria from oxidative damage. These compounds protect mitochondria from
      damage following oral delivery and may therefore form the basis for mitochondria
      protective therapies. Here we review the background and work to date on this
      class of mitochondria-targeted antioxidants.

PMID- 17014365
TI  - Iron homeostasis.
AB  - Iron is needed by all mammalian cells but is toxic in excess. Specialized
      transport mechanisms conduct iron across cellular membranes. These are regulated
      to ensure homeostasis both systemically in living organisms and within individual
      cells. Over the past decade, major advances have been made in identifying and
      characterizing the proteins involved in the transport, handling, and homeostatic
      regulation of iron. Molecular understanding of these processes has provided
      important insights into the pathophysiology of human iron disorders.

PMID- 17014366
TI  - Cross-talk between language processes and overt motor behavior in the first 200
      msec of processing.
AB  - A recently emerging view sees language understanding as closely linked to sensory
      and motor processes. The present study investigates this issue by examining the
      influence of processing action verbs and concrete nouns on the execution of a
      reaching movement. Fine-grained analyses of movement kinematics revealed that
      relative to nouns, processing action verbs significantly affects overt motor
      performance. Within 200 msec after onset, processing action verbs interferes with
      a concurrent reaching movement. By contrast, the same words assist reaching
      movement when processed before movement onset. The cross-talk between language
      processes and overt motor behavior provides unambiguous evidence that action
      words and motor action share common cortical representations and could thus
      suggest that cortical motor regions are indeed involved in action word retrieval.

PMID- 17014367
TI  - The nature of anterior negativities caused by misapplications of morphological
      rules.
AB  - This study investigates functional interpretations of left anterior negativities
      (LANs), a language-related electroencephalogram effect that has been found for
      syntactic and morphological violations. We focus on three possible
      interpretations of LANs caused by the replacement of irregular affixes with
      regular affixes: misapplication of morphological rules, mismatch of the presented
      form with analogy-based expectations, and mismatch of the presented form with
      stored representations. Event-related brain potentials were recorded during the
      visual presentation of existing and novel Dutch compounds. Existing compounds
      contained correct or replaced interfixes (dame + s + salons > damessalons vs.
      *dame + n + salons > *damensalons "women's hairdresser salons"), whereas novel
      Dutch compounds contained interfixes that were either supported or not supported
      by analogy to similar existing compounds (kruidenkelken vs. ?kruidskelken "herb
      chalices"); earlier studies had shown that interfixes are selected by analogy
      instead of rules. All compounds were presented with correct or incorrect regular
      plural suffixes (damessalons vs. *damessalonnen). Replacing suffixes or
      interfixes in existing compounds both led to increased (L)ANs between 400 and 700
      msec without any evidence for different scalp distributions for interfixes and
      suffixes. There was no evidence for a negativity when manipulating the analogical
      support for interfixes in novel compounds. Together with earlier studies, these
      results suggest that LANs had been caused by the mismatch of the presented forms
      with stored forms. We discuss these findings with respect to the single/dual
      route debate of morphology and LANs found for the misapplication of syntactic
      rules.

PMID- 17014368
TI  - On the time course of visual word recognition: an event-related potential
      investigation using masked repetition priming.
AB  - The present study used event-related potentials (ERPs) to examine the time course
      of visual word recognition using a masked repetition priming paradigm.
      Participants monitored target words for occasional animal names, and ERPs were
      recorded to nonanimal critical items that were full repetitions, partial
      repetitions, or unrelated to the immediately preceding masked prime word. The
      results showed a strong modulation of the N400 and three earlier ERP components
      (P150, N250, and the P325) that we propose reflect sequential overlapping steps
      in the processing of printed words.

PMID- 17014369
TI  - The anatomy of category-specific object naming in neurodegenerative diseases.
AB  - Neuropsychological studies suggest that knowledge about living and nonliving
      objects is processed in separate brain regions. However, lesion and functional
      neuroimaging studies have implicated different areas. To address this issue, we
      used voxel-based morphometry to correlate accuracy in naming line drawings of
      living and nonliving objects with gray matter volumes in 152 patients with
      various neurodegenerative diseases. The results showed a significant positive
      correlation between gray matter volumes in bilateral temporal cortices and total
      naming accuracy regardless of category. Naming scores for living stimuli
      correlated with gray matter volume in the medial portion of the right anterior
      temporal pole, whereas naming accuracy for familiarity-matched nonliving items
      correlated with the volume of the left posterior middle temporal gyrus. A
      previous behavioral study showed that the living stimuli used here also had in
      common the characteristic that they were defined by shared sensory semantic
      features, whereas items in the nonliving group were defined by their action
      related semantic features. We propose that the anatomical segregation of living
      and nonliving categories is the result of their defining semantic features and
      the distinct neural subsystems used to process them.

PMID- 17014370
TI  - Differences in mnemonic processing by neurons in the human hippocampus and
      parahippocampal regions.
AB  - Different structures within the medial-temporal lobe likely make distinct
      contributions to declarative memory. In particular, several current psychological
      and computational models of memory predict that the hippocampus and
      parahippocampal regions play different roles in the formation and retrieval of
      declarative memories [e.g., Norman, K. A., & O'Reilly, R. C. Modeling hippocampal
      and neocortical contributions to recognition memory: A complementary-learning
      systems approach. Psychological Review, 110, 611-646, 2003]. Here, we examined
      the neuronal firing patterns in these two regions during recognition memory.
      Recording directly from neurons in humans, we find that cells in both regions
      respond to novel stimuli with an increase in firing (excitation). However,
      already on the second presentation of a stimulus, neurons in these regions show
      very different firing patterns. In the parahippocampal region there is dramatic
      decrease in the number of cells responding to the stimuli, whereas in the
      hippocampus there is recruitment of a large subset of neurons showing inhibitory
      (decrease from baseline firing) responses. These results suggest that inhibition
      is a mechanism used by cells in the human hippocampus to support sparse coding in
      mnemonic processing. The findings also provide further evidence for the division
      of labor in the medial-temporal lobe with respect to declarative memory
      processes.

PMID- 17014371
TI  - A moment to reflect upon perceptual synchrony.
AB  - How does neuronal activity bring about the interpretation of visual space in
      terms of objects or complex perceptual events? If they group, simple visual
      features can bring about the integration of spikes from neurons responding to
      different features to within a few milliseconds. Considered as a potential
      solution to the "binding problem," it is suggested that neuronal synchronization
      is the glue for binding together different features of the same object. This idea
      receives some support from correlated- and periodic-stimulus motion paradigms,
      both of which suggest that the segregation of a figure from ground is a direct
      result of the temporal correlation of visual signals. One could say that
      perception of a highly correlated visual structure permits space to be bound in
      time. However, on closer analysis, the concept of perceptual synchrony is
      insufficient to explain the conditions under which events will be seen as
      simultaneous. Instead, the grouping effects ascribed to perceptual synchrony are
      better explained in terms of the intervals of time over which stimulus events
      integrate and seem to occur simultaneously. This point is supported by the
      equivalence of some of these measures with well-established estimates of the
      perceptual moment. However, it is time in extension and not the instantaneous
      that may best describe how seemingly simultaneous features group. This means that
      studies of perceptual synchrony are insufficient to address the binding problem.

PMID- 17014372
TI  - The "special effect" of case mixing on word identification: neuropsychological
      and transcranial magnetic stimulation studies dissociating case mixing from
      contrast reduction.
AB  - We present neuropsychological and transcranial magnetic stimulation (TMS)
      evidence with normal readers, that the effects of case mixing and contrast
      reduction on word identification are qualitatively different. Lesions and TMS
      applied to the right parietal lobe selectively disrupted the identification of
      mixed relative to single-case stimuli. Bilateral lesions and TMS applied to the
      occipital cortex selectively disrupted the identification of low-contrast words.
      These data suggest that different visual distortions (case mixing, contrast
      reduction) exert different effects on reading, modulated by contrasting brain
      regions. Case mixing is a "special" distortion and involves the recruitment of
      processes that are functionally distinct, and dependent on different regions in
      the brain, from those required to deal with contrast reduction.

PMID- 17014373
TI  - Auditory language comprehension in children with developmental dyslexia: evidence
      from event-related brain potentials.
AB  - In the present study, event-related brain potentials (ERPs) were used to compare
      auditory sentence comprehension in 16 children with developmental dyslexia (age 9
      12 years) and unimpaired controls matched on age, sex, and nonverbal
      intelligence. Passive sentences were presented, which were either correct or
      contained a syntactic violation (phrase structure) or a semantic violation
      (selectional restriction). In an overall sentence correctness judgment task, both
      control and dyslexic children performed well. In the ERPs, control children and
      dyslexic children demonstrated a similar N400 component for the semantic
      violation. For the syntactic violation, control children demonstrated a combined
      pattern, consisting of an early starting bilaterally distributed anterior
      negativity and a late centro-parietal positivity (P600). Dyslexic children showed
      a different pattern that is characterized by a delayed left lateralized anterior
      negativity, followed by a P600. These data indicate that dyslexic children do not
      differ from unimpaired controls with respect to semantic integration processes
      (N400) or controlled processes of syntactic reanalyses (P600) during auditory
      sentence comprehension. However, early and presumably highly automatic processes
      of phrase structure building reflected in the anterior negativity are delayed in
      dyslexic children. Moreover, the differences in hemispheric distribution of the
      syntactic negativity indicate different underlying processes in dyslexic children
      and controls. The bilateral distribution in controls suggests an involvement of
      right hemispherically established prosodic processes in addition to the left
      hemispherically localized syntactic processes, supporting the view that prosodic
      information may be used to facilitate syntactic processing during normal
      comprehension. The left hemispheric distribution observed for dyslexic children,
      in contrast, suggests that these children do not rely on information about the
      prosodic contour during auditory sentence comprehension as much as controls do.
      This finding points toward a phonological impairment in dyslexic children that
      might hamper the development of syntactic processes.

PMID- 17014374
TI  - It's early: event-related potential evidence for initial interaction of syntax
      and prosody in speech comprehension.
AB  - Psycholinguistic theories assume an interaction between prosody and syntax during
      language processing. Based on studies using mostly off-line methods, it is
      unclear whether an interaction occurs at later or initial processing stages.
      Using event-related potentials, the present study provides neurophysiological
      evidence for a prosody and syntax interaction in initial processing. The sentence
      material contained mere prosodic and syntactic as well as combined prosodic
      syntactic violations. For the syntax violation, the critical word appeared after
      a preposition. The suffix of the critical word either indicated a noun fulfilling
      the syntactic requirements of the preceding preposition or a verb causing a word
      category violation. For the prosodic manipulation, congruent critical words were
      normally intonated (signaling sentence continuation) while prosodically
      incongruent critical words signaled sentence end. For the mere prosodic
      incongruity, a broadly distributed negativity was observed at the critical word
      stem (300-500 msec aligned to word onset). In response to a mere syntactic error,
      a left temporal negativity was elicited in an early time window (200-400 msec
      aligned to suffix onset), taken to reflect initial phrase structure building
      processes. In contrast, in response to the combined prosodic-syntactic violation,
      an early temporal negativity showed up bilaterally at the suffix in the same time
      window. Our interpretation is that the process of initial structure building as
      reflected in the early left anterior negativity recruits additional right
      hemispheric neural resources when the critical word contains both syntactic and
      prosodic violations. This suggests the immediate influence of phrasal prosody
      during the initial parsing stage in speech processing.

PMID- 17014375
TI  - Repetitive transcranial magnetic stimulation dissociates working memory
      manipulation from retention functions in the prefrontal, but not posterior
      parietal, cortex.
AB  - Understanding the contributions of the prefrontal cortex (PFC) to working memory
      is central to understanding the neural bases of high-level cognition. One
      question that remains controversial is whether the same areas of the dorsolateral
      PFC (dlPFC) that participate in the manipulation of information in working memory
      also contribute to its short-term retention (STR). We evaluated this question by
      first identifying, with functional magnetic resonance imaging (fMRI), brain areas
      involved in manipulation. Next, these areas were targeted with repetitive
      transcranial magnetic stimulation (rTMS) while subjects performed tasks requiring
      only the STR or the STR plus manipulation of information in working memory. fMRI
      indicated that manipulation-related activity was independent of retention-related
      activity in both the PFC and superior parietal lobule (SPL). rTMS, however,
      yielded a different pattern of results. Although rTMS of the dlPFC selectively
      disrupted manipulation, rTMS of the SPL disrupted manipulation and STR to the
      same extent. rTMS of the postcentral gyrus (a control region) had no effect on
      performance. The implications of these results are twofold. In the PFC, they are
      consistent with the view that this region contributes more importantly to the
      control of information in working memory than to its STR. In the SPL, they
      illustrate the importance of supplementing the fundamentally correlational data
      from neuroimaging with a disruptive method, which affords stronger inference
      about structure-function relations.

PMID- 17014377
TI  - Task switching and novelty processing activate a common neural network for
      cognitive control.
AB  - The abrupt onset of a novel event captures attention away from, and disrupts,
      ongoing task performance. Less obvious is that intentional task switching
      compares with novelty-induced behavioral distraction. Here we explore the
      hypothesis that intentional task switching and attentional capture by a novel
      distracter both activate a common neural network involved in processing
      contextual novelty [Barcelo, F., Perianez, J. A., & Knight, R. T. Think
      differently: A brain orienting response to task novelty. NeuroReport, 13, 1887
      1892, 2002.]. Event-related potentials were recorded in two task-cueing paradigms
      while 16 subjects sorted cards following either two (color or shape; two-task
      condition) or three (color, shape, or number; three-task condition) rules of
      action. Each card was preceded by a familiar tone cueing the subject either to
      switch or to repeat the previous rule. Novel sound distracters were interspersed
      in one of two blocks of trials in each condition. Both novel sounds and task
      switch cues impaired responses to the following visual target. Novel sounds
      elicited novelty P3 potentials with their usual peak latency and frontal-central
      scalp distribution. Familiar tonal switch cues in the three- and two-task
      conditions elicited brain potentials with a similar latency and morphology as the
      novelty P3, but with relatively smaller amplitudes over frontal scalp regions.
      Covariance and principal component analyses revealed a sustained frontal negative
      potential that was distorting concurrent novelty P3 activity to the tonal switch
      cues. When this frontal negativity was statistically removed, P3 potentials to
      novel sounds and task-switch cues showed similar scalp topographies. The degree
      of activation in the novelty P3 network seemed to be a function of the
      information (entropy) conveyed by the eliciting stimulus for response selection,
      over and above its relative novelty, probability of occurrence, task relevance,
      or feedback value. We conclude that novelty P3 reflects transient activation in a
      neural network involved in updating task set information for goal-directed action
      selection and might thus constitute one key element in a central bottleneck for
      attentional control.

PMID- 17014376
TI  - Transverse patterning and human amnesia.
AB  - The transverse patterning (TP) task (A+ B-, B+ C-, C+ A-) has played a central
      role in testing the hypothesis that medial-temporal (and, in particular,
      hippocampal) brain damage selectively impairs learning on at least some classes
      of configural (i.e., nonlinear) learning tasks. Results in the animal and human
      literature generally support that hypothesis. Reed and Squire [Impaired
      transverse patterning in human amnesia is a special case of impaired memory for
      two-choice discrimination tasks. Behavioral Neuroscience, 113, 3-9, 1999],
      however, advanced an alternative account in which impaired TP performance in
      amnesia reflects a generic scaling artifact arising from the greater difficulty
      of the TP task compared to the elemental (i.e., linear) control task that is
      typically used. We begin with a critique of Reed and Squire, countering their
      conceptual arguments and showing that their results, when analyzed appropriately,
      support the configural deficit hypothesis. We then report results from eight new
      amnesic patients and controls on an improved version of the TP task. Despite
      substantial practice, accuracy of patients with bilateral hippocampal damage due
      to anoxia reached and maintained an asymptote of only 54% correct, well below the
      maximum accuracy obtainable (67%) in the absence of configural learning. A
      patient with selective bilateral damage to the anterior thalamic nuclei exhibited
      a TP accuracy asymptote that was near 67%, a pattern of two out of three correct
      consecutive trials, and a pattern of nearly always answering correctly for two of
      the three TP item pairs. These results are consistent with a set of unique and
      parameter-free predictions of the configural deficit hypothesis.

PMID- 17014378
TI  - Magnetic stimulation of the left visual cortex impairs expert word recognition.
AB  - One of the hallmarks of expert reading is the ability to identify arrays of
      several letters quickly and in parallel. Such length-independent reading has only
      been found for word stimuli appearing in the right visual hemifield (RVF). With
      left hemifield presentation (LVF), response times increase as a function of word
      length. Here we investigated the comparative efficiency with which the two
      hemispheres are able to recognize visually presented words, as measured by word
      length effects. Repetitive transcranial magnetic stimulation (rTMS) of the left
      occipital cortex disrupted expert processing of the RVF such that a length effect
      was created (Experiment 1). Right occipital rTMS, on the other hand, had no such
      effect on RVF words and nor did it modulate the length effect already present in
      the LVF. Experiment 2 explored the time course of these TMS-induced effects by
      applying single pulses of TMS at various stimulus-onset asynchronies for the same
      task. We replicated the TMS-induced length effect for RVF words, but only when a
      single pulse was applied to the left visual cortex 80 msec after target
      presentation. This is the first demonstration of TMS-induced impairment producing
      a word length effect, and as such confirms the specialization of the left
      hemisphere in word recognition. It is likely that anatomical differences in the
      pathway linking retinal input to higher level cortical processing drive this
      effect.

PMID- 17014379
TI  - Increased responsiveness to novelty is associated with successful cognitive
      aging.
AB  - The animal literature suggests that exposure to more complex, novel environments
      promotes neurogenesis and cognitive performance in older animals. Studies in
      humans indicate that participation in intellectually stimulating activities may
      serve as a buffer against mental decline and help to sustain cognitive abilities.
      Here, we show that across old adults, increased responsiveness to novel events
      (as measured by viewing duration and the size of the P3 event-related potential)
      is strongly linked to better performance on neuropsychological tests, especially
      those involving attention/executive functions. Cognitively high performing old
      adults generate a larger P3 response to visual stimuli than cognitively average
      performing adults. These results suggest that cognitively high performing adults
      successfully manage the task by appropriating more resources and that the
      increased size of their P3 component represents a beneficial compensatory
      mechanism rather than less efficient processing.

PMID- 17014380
TI  - Mental representation of verb meaning: behavioral and electrophysiological
      evidence.
AB  - Previous psycholinguistic research has debated the nature of the mental
      representation of verbs and the access of relevant verb information in sentence
      processing. In this study, we used behavioral and electrophysiological methods to
      examine the representation of verbs in and out of sentence contexts. In five
      experiments, word naming and event-related potential (ERP) components were used
      to measure the speed and the amplitude, respectively, associated with different
      verb-object combinations that result in different degrees of fit between the verb
      and its object. Both naming speed and ERP amplitudes (N400) are proven to be
      sensitive indices of the degree of fit, varying as a function of how well the
      object fits the verb in terms of selectional restrictions. The results suggest
      that the semantic features of the verb's arguments are an integral part of the
      mental representation of verbs, and such information of the verb is accessed and
      used on-line during sentence processing. Implications of these results are
      discussed in light of recent computational semantic models that view the lexicon
      through high-order lexical co-occurrences in language use.

PMID- 17014381
TI  - Habitual levels of physical activity influence bone mass in 11-year-old children
      from the United Kingdom: findings from a large population-based cohort.
AB  - We examined the influence of habitual levels of physical activity on bone mass in
      childhood by studying the relationship between accelerometer recordings and DXA
      parameters in 4457 11-year-old children. Physical activity was positively related
      to both BMD and bone size in fully adjusted models. However, further exploration
      revealed that this effect on bone size was modified by fat mass. INTRODUCTION:
      Exercise interventions have been reported to increase bone mass in children, but
      it is unclear whether levels of habitual physical activity also influence
      skeletal development. MATERIALS AND METHODS: We used multivariable linear
      regression to analyze associations between amount of moderate and vigorous
      physical activity (MVPA), derived from accelerometer recordings for a minimum of
      3 days, and parameters obtained from total body DXA scans in 4457 11-year-old
      boys and girls from the Avon Longitudinal Study of Parents and Children. The
      influence of different activity intensities was also studied by stratification
      based on lower and higher accelerometer cut-points for moderate (3600
      counts/minute) and vigorous (6200 counts/minute) activity, respectively. RESULTS:
      MVPA was positively associated with lower limb BMD and BMC adjusted for bone area
      (aBMC; p < 0.001, adjusted for age, sex, socio-economic factors, and height, with
      or without additional adjustment for lean and fat mass). MVPA was inversely
      related to lower limb bone area after adjusting for height and lean mass (p =
      0.01), whereas a positive association was observed when fat mass was also
      adjusted for (p < 0.001). Lower limb BMC was positively related to MVPA after
      adjusting for height and lean and fat mass (p < 0.001), whereas little
      relationship was observed after adjusting for height and lean mass alone (p =
      0.1). On multivariable regression analysis using the fully adjusted model,
      moderate activity exerted a stronger influence on lower limb BMC compared with
      light activity (light activity: 2.9 [1.2-4.7, p = 0.001]; moderate activity: 13.1
      [10.6-15.5, p < 0.001]; regression coefficients with 95% confidence intervals and
      p values). CONCLUSIONS: Habitual levels of physical activity in 11-year-old
      children are related to bone size and BMD, with moderate activity exerting the
      strongest influence. The effect on bone size (as reflected by DXA-based measures
      of bone area) was modified by adjustment for fat mass, such that decreased fat
      mass, which is associated with higher levels of physical activity, acts to reduce
      bone size and thereby counteract the tendency for physical activity to increase
      bone mass.

PMID- 17014382
TI  - Recovery from skeletal fluorosis (an enigmatic, American case).
AB  - A 52-year-old man presented with severe neck immobility and radiographic
      osteosclerosis. Elevated fluoride levels in serum, urine, and iliac crest bone
      revealed skeletal fluorosis. Nearly a decade of detailed follow-up documented
      considerable correction of the disorder after removal of the putative source of
      fluoride (toothpaste). INTRODUCTION: Skeletal fluorosis, a crippling bone
      disorder, is rare in the United States, but affects millions worldwide. There are
      no data regarding its reversibility. MATERIALS AND METHODS: A white man presented
      in 1996 with neck immobility and worsening joint pains of 7-year duration.
      Radiographs revealed axial osteosclerosis. Bone markers were distinctly elevated.
      DXA of lumbar spine (LS), femoral neck (FN), and distal one-third radius showed Z
      scores of +14.3, +6.6, and -0.6, respectively. Transiliac crest biopsy revealed
      cancellous volume 4.5 times the reference mean, cortical width 3.2 times the
      reference mean, osteoid thickness 25 times the reference mean, and wide and
      diffuse tetracycline uptake documenting osteomalacia. Fluoride (F) was elevated
      in serum (0.34 and 0.29 mg/liter [reference range: <0.20]), urine (26 mg/liter
      [reference range: 0.2-1.1 mg/liter]), and iliac crest (1.8% [reference range:
      <0.1%]). Tap and bottled water were negative for F. Surreptitious ingestion of
      toothpaste was the most plausible F source. RESULTS: Monitoring for a decade
      showed that within 3 months of removal of F toothpaste, urine F dropped from 26
      to 16 mg/liter (reference range: 0.2-1.1 mg/liter), to 3.9 at 14 months, and was
      normal (1.2 mg/liter) after 9 years. Serum F normalized within 8 months. Markers
      corrected by 14 months. Serum creatinine increased gradually from 1.0 (1997) to
      1.3 mg/dl (2006; reference range: 0.5-1.4 mg/dl). Radiographs, after 9 years,
      showed decreased sclerosis of trabeculae and some decrease of sacrospinous
      ligament ossification. DXA, after 9 years, revealed 23.6% and 15.1% reduction in
      LS and FN BMD with Z scores of +9.3 and +4.8, respectively. Iliac crest, after
      8.5 years, had normal osteoid surface and thickness with distinct double labels.
      Bone F, after 8.5 years, was 1.15% (reference range, <0.1), which was a 36%
      reduction (still 10 times the reference value). All arthralgias resolved within 2
      years, and he never fractured, but new-onset nephrolithiasis occurred within 9
      months and became a chronic problem. CONCLUSIONS: With removal of F exposure,
      skeletal fluorosis is reversible, but likely impacts for decades. Patients should
      be monitored for impending nephrolithiasis.

PMID- 17014383
TI  - Double-stranded RNA-dependent protein kinase is involved in 2-methoxyestradiol
      mediated cell death of osteosarcoma cells.
AB  - We studied the involvement of interferon-regulated, PKR on 2-ME-mediated actions
      in human osteosarcoma cells. Our results show that PKR is activated by 2-ME
      treatment and is necessary for 2-ME-mediated induction of osteosarcoma cell
      death. INTRODUCTION: Osteosarcoma is the most common primary bone tumor and most
      frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a metabolite
      of 17beta-estradiol, induces interferon gene expression and apoptosis in human
      osteosarcoma cells. In this report, we studied the role of interferon-regulated
      double-stranded (ds)RNA-dependent protein kinase (PKR) protein on 2-ME-mediated
      cell death in human osteosarcoma cells. MATERIALS AND METHODS: Western blot
      analyses were used to measure PKR protein and phosphorylation levels. Cell
      survival and apoptosis assays were measured using trypan blue exclusion and
      Hoechst dye methods, respectively. A transient transfection protocol was used to
      express the dominant negative PKR mutants. RESULTS AND CONCLUSIONS: PKR was
      increased in 2-ME-treated MG63 cells, whereas 17beta-estradiol, 4
      hydroxyestradiol, and 16alpha-hydroxyestradiol, which do not induce cell death,
      had no effect on PKR protein levels. Also, 2-ME treatment induced PKR kinase
      activity as indicated by increased autophosphorylation and phosphorylation of the
      endogenous substrate, eukaryotic initiation factor (eIF)-2alpha. dsRNA poly
      (I).poly (C), an activator of PKR protein, increased cell death when osteosarcoma
      cells were treated with a submaximal concentration of 2-ME. In contrast, a serine
      threonine kinase inhibitor SB203580 and a specific PKR inhibitor 2-aminopurine (2
      AP) blocked the 2-ME-induced cell death in MG63 cells. A dominant negative PKR
      mutant protein conferred resistance to 2-ME-induced cell death to MG63
      osteosarcoma and 2-ME-mediated PKR regulation did not require interferon gene
      expression. PKR protein is activated in cell free extracts by 2-ME treatment,
      resulting in autophosphorylation and in the phosphorylation of the substrate eIF
      2alpha. We conclude from these results that PKR is regulated by 2-ME
      independently of interferon and is essential for 2-ME-mediated cell death in MG63
      osteosarcoma cells.

PMID- 17014384
TI  - Co-treatment of PTH with osteoprotegerin or alendronate increases its anabolic
      effect on the skeleton of oophorectomized mice.
AB  - We examined the effects of 60 days of co-treatment of PTH with either OPG or
      alendronate in oophorectomized mice. Compared with PTH alone, co-treatment of PTH
      with either of these two mechanistically distinct anti-catabolics improved bone
      volume, mechanical strength, and appendicular and axial mineralization and
      prolonged the beneficial effect of PTH on BMD. INTRODUCTION: Conflicting evidence
      exists as to whether the anabolic effect of PTH is inhibited by the action of
      anti-catabolics. To examine this issue, we assessed the effects of alendronate
      and osteoprotegerin (OPG), two anti-catabolics with different modes of action, on
      the anabolic activity of PTH(1-34) in the skeleton of 4-month-old oophorectomized
      mice. MATERIALS AND METHODS: Mice treated with vehicle alone (PBS), alendronate
      alone (100 microg/kg/week), OPG alone (10 mg/kg twice a week), or PTH alone (80
      microg/kg/day) were compared with each other and with animals administered PTH
      plus alendronate or PTH plus OPG. We assessed lumbar spine and femoral BMD at 0,
      30, and 60 days. Contact radiography, histology, and histomorphometry, three
      point bending assay of the femur, and serum osteocalcin and TRACP5b assays were
      performed at 2 months. RESULTS: Although alendronate and OPG each suppressed bone
      turnover, at the doses used, this was more profound with OPG. Increases in lumbar
      spine and femoral BMD and in trabecular bone volume were at least as great with
      OPG as with alendronate, and mechanical indices of femoral bone strength improved
      only with OPG. Both produced a plateau in spine and femoral BMD increases by 30
      days. Co-treatment of PTH with each anti-catabolic produced additive increases in
      BMD in the femur and supra-additive increases in the lumbar spine with no plateau
      effects. Neither anti-catabolic impeded the PTH-induced increase in bone volume
      or the increase in mechanical strength of the femur. CONCLUSIONS: These studies
      show that the highly potent anti-catabolic OPG can produce dramatic increases in
      BMD and bone strength; that the temporal pattern of activity of bone formation
      and resorption modulators may have major influence on net skeletal accrual; and
      that, depending on timing, inhibition of osteoclastic activity may markedly
      augment the anabolic action of PTH.

PMID- 17014385
TI  - Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice
      during puberty.
AB  - The interaction between androgens and GH/IGF-I was studied in male GHR gene
      disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and
      cortical bone modeling and increase muscle mass even in the absence of a
      functional GHR. GHR activation seems to be the main determinant of radial bone
      expansion, although GH and androgens are both necessary for optimal stimulation
      of periosteal growth during puberty. INTRODUCTION: Growth hormone (GH) is
      considered to be a major regulator of postnatal skeletal growth, whereas
      androgens are considered to be a key regulator of male periosteal bone expansion.
      Moreover, both androgens and GH are essential for the increase in muscle mass
      during male puberty. Deficiency or resistance to either GH or androgens impairs
      bone modeling and decreases muscle mass. The aim of the study was to investigate
      androgen action on bone and muscle during puberty in the presence and absence of
      a functional GH/insulin-like growth factor (IGF)-I axis. MATERIALS AND METHODS:
      Dihydrotestosterone (DHT) or testosterone (T) were administered to
      orchidectomized (ORX) male GH receptor gene knockout (GHRKO) and corresponding
      wildtype (WT) mice during late puberty (6-10 weeks of age). Trabecular and
      cortical bone modeling, cortical strength, body composition, IGF-I in serum, and
      its expression in liver, muscle, and bone were studied by histomorphometry, pQCT,
      DXA, radioimmunoassay and RT-PCR, respectively. RESULTS: GH receptor (GHR)
      inactivation and low serum IGF-I did not affect trabecular bone modeling, because
      trabecular BMD, bone volume, number, width, and bone turnover were similar in
      GHRKO and WT mice. The normal trabecular phenotype in GHRKO mice was paralleled
      by a normal expression of skeletal IGF-I mRNA. ORX decreased trabecular bone
      volume significantly and to a similar extent in GHRKO and WT mice, whereas DHT
      and T administration fully prevented trabecular bone loss. Moreover, DHT and T
      stimulated periosteal bone formation, not only in WT (+100% and +100%,
      respectively, versus ORX + vehicle [V]; p < 0.05), but also in GHRKO mice (+58%
      and +89%, respectively, versus ORX + V; p < 0.05), initially characterized by
      very low periosteal growth. This stimulatory action on periosteal bone resulted
      in an increase in cortical thickness and occurred without any treatment effect on
      serum IGF-I or skeletal IGF-I expression. GHRKO mice also had reduced lean body
      mass and quadriceps muscle weight, along with significantly decreased IGF-I mRNA
      expression in quadriceps muscle. DHT and T equally stimulated muscle mass in
      GHRKO and WT mice, without any effect on muscle IGF-I expression. CONCLUSIONS:
      Androgens stimulate trabecular and cortical bone modeling and increase muscle
      weight independently from either systemic or local IGF-I production. GHR
      activation seems to be the main determinant of radial bone expansion, although
      GHR signaling and androgens are both necessary for optimal stimulation of
      periosteal growth during puberty.

PMID- 17014386
TI  - Oncogenic osteomalacia: exact tumor localization by co-registration of positron
      emission and computed tomography.
AB  - In oncogenic osteomalacia, the causative tumor is almost always difficult to
      find. A novel diagnostic approach is presented that facilitates a precise and
      rapid localization of the associated lesion by PET-CT co-registration using the
      radiotracer (68)Ga-DOTANOC. INTRODUCTION: Oncogenic osteomalacia (OOM) is an
      uncommon disorder characterized by hyperphosphaturia, hypophosphatemia, decreased
      vitamin D(3) serum levels, and osteomalacia. The paraneoplastic syndrome is
      exclusively driven by a small somatostatin receptor (sst)-positive tumor that
      produces phosphatonins, proteins that cause renal phosphate loss. OOM can be
      cured completely on tumor removal. However, the exact tumor localization is the
      most challenging step, because the lesion is notoriously difficult to detect by
      common imaging techniques. MATERIALS AND METHODS: A 60-year-old woman complained
      of severe pain in her back and chest wall, muscle weakness, and reduced physical
      activity for >1 year. She suffered a metatarsal fracture and presented with
      hyperphosphaturia and hypophosphatemia. OOM was suspected, and a meticulous
      search for the tumor was initiated by conventional imaging techniques, sst
      mediated imaging using (111)In-octreotide scintigraphy, and (68)Ga-DOTANOC-based
      positron emission tomography (PET)-CT co-registration. (68)Ga-DOTANOC is a novel
      radiopharmaceutical compound in which the somatostatin analog octreotide is
      modified at position 3, chelated with DOTA, and complexed with (68)Gallium.
      (68)Ga-DOTANOC has an improved affinity to sst2 and sst5 relative to other
      radiopeptides. RESULTS: Whereas common imaging techniques such as CT failed to
      localize the tumor, (111)In-octreotide scintigraphy was able to detect the
      lesion, but only PET-CT using (68)Ga-DOTANOC revealed the exact tumor
      localization in the right femoral head. On tumor resection, the well being of the
      patient improved significantly, and biochemical parameters returned to normal.
      CONCLUSIONS: (68)Ga-DOTANOC-based PET-CT is a novel and powerful approach to
      detect sst-positive tumors in a timely manner and to provide highly resolved
      images facilitating the development of a therapeutic strategy.

PMID- 17014387
TI  - Genetic polymorphisms of drug transporters: pharmacokinetic and pharmacodynamic
      consequences in pharmacotherapy.
AB  - There has been increasing appreciation of the role of drug transporters in
      pharmacokinetic and pharmacodynamic consequences in pharmacotherapy. The clinical
      relevance of drug transporters depends on the localisation in human tissues
      (i.e., vectorial movement), the therapeutic index of the substrates and inherent
      interindividual variability. With regard to variability, polymorphisms of drug
      transporter genes have recently been reported to be associated with alterations
      in the pharmacokinetics and pharmacodynamics of clinically useful drugs. A
      growing number of preclinical and clinical studies have demonstrated that the
      application of genetic information may be useful in individualised
      pharmacotherapy for numerous diseases. However, the reported effects of variants
      in certain drug transporter genes have been inconsistent and, in some cases,
      conflicting among studies. Furthermore, the incidence of almost all known
      variants in transporter genes tends to be racially dependent. These observations
      suggest the necessity of considering interethnic variability before extrapolating
      pharmacokinetic data obtained in one ethic group to another, especially in the
      early phase of drug development. This review focuses on the impact of genetic
      variations in the function of drug transporters (ABC, organic anion and cation
      transporters) and the implications of these variations for pharmacotherapy from
      pharmacokinetic and pharmacodynamic viewpoints.

PMID- 17014388
TI  - Strategies to assess the drug interaction potential in translational medicine.
AB  - Translational medicine is the drug development phase in which preclinical and
      clinical applied research is conducted to aid dose and disease selection with
      great financial impact. Thus, during this phase, early discontinuation of a drug
      that will later fail due to drug interactions is a must for a proper resource
      allocation. It is not only important to identify a potential interaction, but
      also to be able to differentiate between detectable interactions and clinically
      relevant interactions. Due to the scientific advancement, the prediction of drug
      interactions during translational medicine has shifted from
      empirical/observational to rational based. These investigations are thus in line
      with the FDA's Critical Path Initiative and are facilitated by the availability
      of mature technologies and by current European and US guidelines for both in
      vitro and in vivo studies. Because drug interactions must be evaluated in a
      multidisciplinary fashion, even if these studies are contracted externally,
      pharmaceutical companies should be directly involved in the conduction of such
      studies to fully exploit their potential and to allow a better and faster
      interpretation of the results.

PMID- 17014389
TI  - In vitro assays and biomarkers for drug-induced phospholipidosis.
AB  - Drug-induced phospholipidosis is the cytoplasmic accumulation of phospholipids as
      a result of xenobiotic exposure. This accumulation results in a unique
      histological effect in cells noted as electron-dense lamellar inclusions or
      whorls in the cytoplasm when observed with transmission electron microscopy.
      Electron microscopy has been the widely accepted standard for classification of
      the phospholipidosis effect. Molecules that have been prone to induce such an
      effect are made up of a lipophilic region and a positively charged region.
      Phospholipidosis has most commonly been associated with drugs that are cationic,
      amphiphilic drugs and can occur in a variety of tissues. Although
      phospholipidosis is not considered adverse in isolation, depending on the tissue
      affected or the occasional circumstance of concurrent toxicity, phospholipidosis
      can be perplexing if identified in early drug development. In most circumstances,
      characterisation of the effect with in vivo studies allows for determination of
      exposure and the magnitude of the effect. On occasion in drug development, there
      may be an interest to screen early stage compounds to minimise phospholipidosis.
      In such circumstances, in silico and in vitro assays can be employed in a
      strategy with in vivo assessments. In addition, there may be an interest to
      monitor for the potential development of phospholipidosis in longer-term animal
      studies. In such cases, biomarker approaches could be used. The challenge in the
      overall assessment of phospholipidosis remains the question of the possible
      relevance to any toxicity, and, therefore, any screening approach, while
      assessing the potential to induce phospholipidosis, must be considered in
      relation to prediction of findings in vivo. The status of current assays and
      biomarkers is presented with strategies for screening.

PMID- 17014390
TI  - Mechanistic biomarkers for cytotoxic acute kidney injury.
AB  - Acute kidney injury is a common condition and is associated with a high mortality
      rate. It has been recognised that routinely used measures of renal function, such
      as levels of blood urea nitrogen and serum creatinine, increase significantly
      only after substantial kidney injury occurs and then with a time delay.
      Insensitivity of such tests delays the diagnosis in humans, making it
      particularly challenging to administer putative therapeutic agents in a timely
      fashion. Furthermore, this insensitivity affects the evaluation of toxicity in
      preclinical studies by allowing drug candidates, which have low, but nevertheless
      important, nephrotoxic side effects in animals, to pass the preclinical safety
      criteria only to be found to be clinically nephrotoxic with great human costs.
      This review presents the current status of sensitive and specific biomarkers to
      detect preclinical and clinical renal injury and summarises the techniques used
      to quantitate these biomarkers in biological fluids.

PMID- 17014391
TI  - Preclinical formulations for discovery and toxicology: physicochemical
      challenges.
AB  - Formulations play a key role in assessing the biological properties of a molecule
      during drug discovery. Maximising exposure is the primary objective in early
      animal experimentation, so that the pharmacokinetics, pharmacodynamics and
      toxicological signals can be put into context with the biological response to
      specific targets. Consistency in the exposure is also a key aspect, and effective
      formulation and drug delivery strategies are important to achieve this. Diversity
      in the physiology between various animal species, routes of administration and
      limitations posed by specific pharmacological models make formulation development
      that much more challenging. Poor physicochemical properties of compounds in the
      early stages need to be kept under consideration while screening for formulation
      vehicles. This review captures the various challenges posed at different stages
      of drug discovery for formulation of a compound to dose in animals. Approaches to
      formulations for various routes of administration are discussed. Limitations
      posed by the goals for various animal studies such as early efficacy studies,
      pharmacokinetic studies and toxicology studies are identified and some strategies
      are proposed. Physicochemical characterisations that are needed to select
      formulation vehicles as well as to identify potential issues are suggested.

PMID- 17014392
TI  - Enhancement of drug absorption by noncharged detergents through membrane and P
      glycoprotein binding.
AB  - Noncharged detergents are used as excipients in drug formulations. Until
      recently, they were considered as inert compounds, enhancing drug absorption
      essentially by improving drug solubility. However, many detergents insert into
      lipid membranes, although to different extents, and change the lateral packing
      density of membranes at high concentrations. Moreover, they bind to the efflux
      transporter P-glycoprotein (P-gp) and most likely to related transporters and
      metabolising enzymes with overlapping substrate specificities. If their affinity
      to P-gp is higher than that of the coadministered drug they act as modulators or
      inhibitors of P-gp and enhance drug absorption. Inhibition of P-gp and related
      proteins can, however, cause severe side effects. This paper first reviews the
      membrane binding propensity of different noncharged detergents (including
      poloxamers) and discusses their ability to bind to P-gp. Second, literature data
      on drug uptake enhancement by noncharged detergents, obtained in vivo and in
      vitro, are analysed at the molecular level. The present analysis provides the
      tools for an approximate and simple prior estimate of the membrane and P-gp
      binding ability of noncharged detergents based on a modular binding approach.

PMID- 17014393
TI  - Therapeutic resistance in lung cancer.
AB  - Despite considerable progress over the last 25 years in the systemic therapy of
      lung cancer, intrinsic and acquired resistance to chemotherapeutic agents and
      radiation remains a vexing problem. The number of mechanisms of therapeutic
      resistance in lung cancer has expanded considerably over the past three decades,
      and the crucial role of stress resistance pathways is increasingly recognised as
      a cause of intrinsic and acquired chemo- and radiotherapy resistance. This paper
      reviews recent evidence for stress defence proteins, particularly RALBP1/RLIP76,
      in mediating intrinsic and acquired chemotherapy and radiation resistance in
      human lung cancer.

PMID- 17014394
TI  - Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) in
      diabetes mellitus.
AB  - Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) is a
      prandial insulin approved in the EU and the US for the treatment of adults with
      diabetes. Its glycaemic control is comparable to subcutaneous insulin in Type 1
      and 2 diabetes, and has superior efficacy versus oral antidiabetic agents in Type
      2 diabetes. Hypoglycaemia and mild-to-moderate cough are the main side effects.
      The treatment group differences in pulmonary function occur early, and are small,
      nonprogressive for up to 2 years and reversible following discontinuation.
      Patient-reported outcomes data displays higher diabetes treatment satisfaction,
      improvements in some quality-of-life scores, and treatment preference with
      inhaled human insulin versus traditional means. Availability of inhaled insulin
      may increase insulin acceptance and thus improve glycaemic control in patients
      with diabetes.

PMID- 17014395
TI  - Insulin aspart: a review.
AB  - Insulin aspart, an analogue of human insulin, which is approved for use in people
      with diabetes, is more rapidly absorbed and achieves higher plasma concentrations
      than human soluble insulin following subcutaneous injection. Hence, it has a
      faster and more effective glucose-lowering action, with superior control of
      postprandial hyperglycaemia compared with human soluble insulin. Its shorter
      duration of action makes interprandial and nocturnal hypoglycaemia less of a
      problem than with human soluble insulin. Insulin aspart is approved for use in
      continuous subcutaneous infusion and offers a valuable treatment option during
      pregnancy.

PMID- 17014396
TI  - A hierarchical screening methodology for physicochemical/ADME/Tox profiling.
AB  - Full integration of pharmaceutical profiling into pharmaceutical lead selection
      and optimisation requires that complete sets of unequivocal data be available at
      the time compound design or advancement decisions are made. As the productivity
      of chemical synthesis expands, and the breadth of profiling assays grow in scope,
      physicochemical/ADME/Tox laboratories are being challenged to produce ever more
      data to support an accelerating decision cycle. This article focuses on the
      challenges of increasing preclinical profiling productivity while managing lower
      accuracy higher throughput data streams to preserve confidence in decision
      making. The authors propose a hierarchical screening strategy and describe the
      implementation of an automated system designed to support that strategy
      efficiently.

PMID- 17014397
TI  - Health and medical research funding: an investment in Australia's future.

PMID- 17014398
TI  - Medical staff working the night shift: can naps help?

PMID- 17014399
TI  - Vertebroplasty: a promising but as yet unproven intervention for painful
      osteoporotic spinal fractures.

PMID- 17014400
TI  - Rotavirus vaccine--time to act.

PMID- 17014401
TI  - Rotavirus gastroenteritis in the Northern Territory, 1995-2004.
AB  - OBJECTIVE: To present data on rotavirus notifications in the Northern Territory
      to provide knowledge about the local epidemiology of rotavirus gastroenteritis
      that can be used to inform the use and funding of rotavirus vaccines. DESIGN:
      Retrospective analysis of data from the Northern Territory Notifiable Diseases
      Database. PARTICIPANTS AND SETTING: Patients with cases of rotavirus infection
      notified to the NT Centre for Disease Control from 1 January 1995 to 31 December
      2004. MAIN OUTCOME MEASURES: Patterns of rotavirus notifications over time;
      infection rates in Indigenous versus non-Indigenous children aged 0-5 years; age
      groups infected with rotavirus. RESULTS: Numbers of rotavirus notifications over
      the period 1995-2004 show annual, monthly and regional variability. The rotavirus
      notification rate for Indigenous children aged 0-5 years was 2.75 per 100 per
      year, compared with 0.98 for non-Indigenous children, with a relative risk for
      Indigenous children of 2.17 (95% CI, 1.97-2.39) over the 10 years. Indigenous
      children infected with rotavirus were younger than non-Indigenous children, with
      median ages of 11 months and 16 months, respectively. Rotavirus gastroenteritis
      occurred in outbreaks, transmitted over months throughout the NT. CONCLUSION:
      Large numbers of cases of rotavirus gastroenteritis affecting Indigenous and non
      Indigenous children in the NT are notified every year. The rate in Indigenous
      children may be decreasing relative to non-Indigenous children. An effective
      rotavirus vaccine could prevent significant morbidity.

PMID- 17014402
TI  - A comparison of the mental health of refugees with temporary versus permanent
      protection visas.
AB  - OBJECTIVES: To determine the impact of the Australian provisions for temporary
      rather than permanent protection for asylum seekers found to be genuine refugees.
      DESIGN AND SETTING: A comparison of the mental health of Persian-speaking
      refugees with temporary (n = 49) versus permanent (n = 67) protection visas
      attending an early intervention program in Sydney, New South Wales, 2002-03.
      MEASURES: Standard measures were used to assess past trauma, detention
      experiences, postmigration stresses, symptoms of post-traumatic stress disorder
      (PTSD), anxiety, depression and functional impairment. RESULTS: The two groups
      had experienced similar levels of past trauma and persecution. Nevertheless,
      holders of temporary protection visas (TPVs) returned higher scores on three
      psychiatric symptom measures (P < 0.001). Multivariate analyses showed that TPV
      status was the strongest predictor of anxiety, depression and particularly PTSD.
      Further analyses suggested that, for TPV holders, experience of past stresses in
      detention in Australia and ongoing living difficulties after release contributed
      to adverse psychiatric outcomes. CONCLUSIONS: The sequence of postmigration
      stresses experienced by TPV holders appears to impact adversely on their mental
      health.

PMID- 17014403
TI  - Use of drug-eluting stents in Victorian public hospitals.
AB  - OBJECTIVE: We aimed to assess the pattern of use of drug-eluting stents (DESs) in
      patients undergoing percutaneous coronary interventions (PCIs) in Victorian
      public hospitals. DESIGN, SETTING AND PATIENTS: Prospective study comparing the
      use of one or more DESs versus bare-metal stents (BMSs) only, in consecutive
      patients undergoing 2428 PCIs with stent implantation from 1 April 2004 to 31
      December 2005 at seven Victorian public hospitals. MAIN OUTCOME MEASURES:
      Adherence to current Victorian Department of Human Services guidelines which
      recommend DES use in patients with high-risk features for restenosis (diabetes,
      small vessels, long lesions, in-stent restenotic lesions, chronic total
      occlusions and bifurcation lesions). RESULTS: Of the 2428 PCIs performed, at
      least one DES was implanted in 1101 (45.3%) and BMSs only were implanted in 1327
      (54.7%). In 87.7% (966/1101) of PCI with DESs, there was at least one criterion
      for high risk of restenosis. DESs were more likely to be used in patients with
      diabetes (risk ratio [RR], 2.45; 95% CI, 2.02-2.97), small vessels (RR, 3.35;
      95%CI, 2.35-4.76), long lesions (RR, 3.87; 95% CI, 3.23-4.65), in-stent
      restenotic lesions (RR, 3.98; 95%CI, 2.67-6.06), chronic total occlusions (RR,
      1.30; 95% CI, 0.51-2.88) and bifurcation lesions (RR, 2.23; 95%CI, 1.57-3.17).
      However, 66.2% (1608/2428) of all PCIs were in patients eligible for DESs
      according to Victorian guidelines, and in 39.9% (642/1608) of these PCIs, a BMS
      was used. CONCLUSION: In Victorian public hospitals, DESs have been largely
      reserved for patients at high risk of restenosis in accordance with Department of
      Human Services guidelines. However, many patients with high-risk criteria for
      restenosis did not receive DESs. Greater use of DESs in these patients may
      improve outcomes by reducing the need for repeat revascularisation.

PMID- 17014404
TI  - Effectiveness of complementary and self-help treatments for depression in
      children and adolescents.
AB  - OBJECTIVE: To review the evidence for the effectiveness of complementary and self
      help treatments for depression in children and adolescents. DATA SOURCES:
      Systematic literature search using PubMed, PsycINFO and the Cochrane Library for
      131 treatments up to February 2006. STUDY SELECTION: There were 13 treatments
      that had been evaluated in intervention studies. DATA EXTRACTION: Studies on each
      treatment were reviewed by one author and checked by a second. A consensus was
      reached for level of evidence. DATA SYNTHESIS: Relevant evidence was available
      for glutamine, S-adenosylmethionine, St John's wort, vitamin C, omega-3 fatty
      acids, light therapy, massage, art therapy, bibliotherapy, distraction
      techniques, exercise, relaxation therapy and sleep deprivation. However, the
      evidence was limited and generally of poor quality. The only treatment with
      reasonable supporting evidence was light therapy for winter depression.
      CONCLUSIONS: Given that antidepressant medication is not recommended as a first
      line treatment for children and adolescents with mild to moderate depression, and
      that the effects of psychological treatments are modest, there is a pressing need
      to extend the range of treatments available for this age group.

PMID- 17014405
TI  - The "therapeutic footprint" of medical, complementary and alternative therapies
      and a doctor's duty of care.
AB  - Complex societal factors unrelated to evidence of efficacy influence the
      increasing use of complementary and alternative therapies, which can be viewed as
      one form of health consumerism. The "therapeutic footprint" is a conceptual model
      that "plots" medical therapies and complementary and alternative therapies in
      relationship to one another and to their levels of risk and supporting evidence,
      acknowledging that medical therapies also entail risks. Philosophies about
      management of risk and adverse effects differ between complementary and
      alternative therapies and standard medical care, due to fundamental differences
      between professionalism within medicine and the demands of health consumerism. In
      standard medical care, patients' risks are mediated prior to treatment via the
      doctor-patient relationship and informed consent. With complementary and
      alternative therapies, protection mechanisms for consumers come into effect
      mainly after a problem has occurred. Understanding this difference helps doctors
      whose patients are using complementary or alternative therapies to define the
      boundaries between these therapies and professional medicine and provide
      appropriate disclosure of risks. Discussing complementary and alternative
      therapies and how they differ from standard medical care can provide
      opportunities to explore patients' concerns and improve the therapeutic
      relationship.

PMID- 17014406
TI  - Integrating complementary therapies into mainstream cancer care: which way
      forward?
AB  - Although viewed with scepticism by the medical and scientific community,
      complementary and alternative medicine (CAM) is being used by about 50% of
      Australians. Integrative medicine is a holistic approach to cancer care, with
      some CAM of proven effectiveness being used as adjuvants to conventional medical
      treatments. However, there is little evidence of a systematic process of
      evaluation or dialogue between mainstream cancer medicine and CAM providers in
      Australia. Collaboration, guidance and support for relevant research in this area
      are needed. The key elements of a process of furthering integrative medicine
      include improving knowledge about CAM; addressing uncertainties about CAM
      efficacy and safety; improving communication about CAM between medical
      practitioners and patients, and between medical practitioners and CAM
      practitioners; introducing regulatory frameworks and credentialing of CAM
      practitioners; and addressing ethical issues.

PMID- 17014407
TI  - Alzheimer's disease and frontotemporal dementia: prospects of a tailored therapy?
AB  - Alzheimer's disease (AD) is the most prevalent dementia (accounting for 50%-75%
      of cases of dementia in people aged over 65 years), followed by frontotemporal
      dementia (FTD) (10%-20% of cases). AD is characterised histopathologically by
      Abeta-containing amyloid plaques and tau-containing neurofibrillary tangles,
      whereas FTD exhibits neurofibrillary tangles alone. Current symptomatic
      treatments of AD are of limited benefit, as they are not directed at the
      underlying biological basis of the disease. The development of transgenic animal
      models has provided insight into disease mechanisms and helped define novel drug
      targets. More than 50 drugs are currently in clinical trials, and novel and more
      effective drugs targeting both AD and FTD are expected to become available within
      5-10 years.

PMID- 17014408
TI  - Accidental death from acute selenium poisoning.
AB  - We report a fatal case of acute selenium poisoning in a 75-year-old man. After
      reading on the Internet about a possible role of selenium in prostate cancer, the
      patient ingested 10 g of sodium selenite. Despite intensive care treatment, he
      suffered a cardiac arrest and died 6 hours after ingestion. This case illustrates
      the risks of failing to critically evaluate Internet information and exposes the
      myth that natural therapies are inherently safe.

PMID- 17014409
TI  - Royal Darwin Hospital Emergency Department, Monday 14 October 2002: a medical
      student's memoir.

PMID- 17014410
TI  - 4. Food allergy in childhood.
AB  - Food allergies in children present with a wide spectrum of clinical
      manifestations, including anaphylaxis, urticaria, angioedema, atopic dermatitis
      and gastrointestinal symptoms (such as vomiting, diarrhoea and failure to
      thrive). Symptoms usually begin in the first 2 years of life, often after the
      first known exposure to the food. Immediate reactions (occurring between several
      minutes and 2 hours after ingestion) are likely to be IgE-mediated and can
      usually be detected by skin prick testing (SPT) or measuring food-specific serum
      IgE antibody levels. Over 90% of IgE-mediated food allergies in childhood are
      caused by eight foods: cows milk, hens egg, soy, peanuts, tree nuts (and seeds),
      wheat, fish and shellfish. Anaphylaxis is a severe and potentially life
      threatening form of IgE-mediated food allergy that requires prescription of self
      injectable adrenaline. Delayed-onset reactions (occurring within several hours to
      days after ingestion) are often difficult to diagnose. They are usually SPT
      negative, and elimination or challenge protocols are required to make a
      definitive diagnosis. These forms of food allergy are not usually associated with
      anaphylaxis. The mainstay of diagnosis and management of food allergies is
      correct identification and avoidance of the offending antigen. Children often
      develop tolerance to cows milk, egg, soy and wheat by school age, whereas
      allergies to nuts and shellfish are more likely to be lifelong.

PMID- 17014411
TI  - Eosinophilic oesophagitis.

PMID- 17014412
TI  - Increase in caesarean section rates among low-risk women in Queensland, 1990
      2004.

PMID- 17014413
TI  - Decline in meningitis admissions in young children: vaccines make a difference.

PMID- 17014414
TI  - Nephrotic-range proteinuria in the obese patient.

PMID- 17014415
TI  - Barriers to student access to patients in a group of teaching hospitals.

PMID- 17014416
TI  - Do advance care directives improve acute care services for older people?

PMID- 17014417
TI  - Birth centre trials are unreliable.

PMID- 17014418
TI  - Research is needed before GPs can engage in "positive" family planning.

PMID- 17014419
TI  - Myotrophin is a more powerful predictor of major adverse cardiac events following
      acute coronary syndrome than N-terminal pro-B-type natriuretic peptide.
AB  - Myotrophin is a 12 kDa protein initially isolated from hypertrophied hearts of
      spontaneously hypertensive rats and acts by modulating NF-kappaB (nuclear factor
      kappaB) activity. We have reported previously the presence of myotrophin in
      patients with human systolic heart failure; however, its role as a predictor of
      MACE (major adverse cardiac events) in patients with ACS (acute coronary
      syndrome) is unclear. In the present study, we sought to investigate this and
      compared myotrophin with NTproBNP (N-terminal pro-B-type natriuretic peptide), a
      marker of MACE. We studied 356 patients with ACS {276 men; mean age, 63.0+/-12.8
      years; 80.6% STEMI [ST segment elevation MI (myocardial infarction)]; and 19.4%
      NSTEMI (non-STEMI)}. Blood measurement was made at 25-48 h after the onset of
      chest pain. The plasma concentration of myotrophin and NTproBNP was determined
      using in-house non-competitive immunoassays. Patients were followed-up for the
      combined end point of death, MI or need for urgent revascularization. Over the
      median follow-up period of 355 (range 0-645) days, there were 28 deaths, 27 non
      fatal MIs and 73 patients required urgent revascularization. Myotrophin was
      raised in patients with MACE compared with survivors [510.7 (116.0-7445.6)
      fmol/ml compared with 371.5 (51.8-6990.4) fmol/ml respectively; P=0.001; values
      are medians (range)]. Using a Cox proportional hazards model, myotrophin {HR
      (hazard ratio), 1.64 [95% CI (confidence interval), 0.97-2.76]; P=0.05} and
      Killip class above 1 [HR, 1.52 (95% CI, 0.93-2.42); P=0.10] were the only
      independent predictors of MACE. A Kaplan-Meier survival curve revealed a
      significantly better clinical outcome in patients with myotrophin below the
      median compared with those with myotrophin above the median (log rank, 7.63;
      P=0.006). In conclusion, after an ACS, levels of myotrophin are more informative
      at predicting MACE than NTproBNP and may be useful to risk stratify patients.

PMID- 17014420
TI  - Morphology and ultrastructure of Siberian sturgeon (Acipenser baerii) spermatozoa
      using scanning and transmission electron microscopy.
AB  - BACKGROUND INFORMATION: Available data concerning the sperm morphology of teleost
      fishes demonstrate wide variation. In the present study, the spermatozoa of
      Siberian sturgeon (Acipenser baerii Brandt, 1869), a chondrostean fish, was
      investigated. In contrast with teleost fish, chondrostean spermatozoa have a head
      with a distinct acrosome, whereas other structures, such as a midpiece and a
      single flagellum, are present in spermatozoa of most species. RESULTS: The
      average length of the head including the acrosome and the midpiece was 7.01+/
      0.83 microm. Ten posterolateral projections derived from the acrosome were
      present on a subacrosomal region, with mean lengths of 0.94+/-0.15 microm and
      widths of 0.93+/-0.11 microm. The nucleus consisted of electrodense homogeneous
      nuclear chromatin. Three intertwining endonuclear canals, bound by membranes,
      traversed the nucleus longitudinally from the acrosomal end to the basal nuclear
      fossa region. There were between three and six mitochondria, two types of
      centrioles (proximal and distal) in the midpiece and two vacuoles composed of
      lipid droplets. The flagellum (44.75+/-4.93 microm in length), originating from
      the centriolar apparatus, had a typical 9+2 eukaryotic flagellar organization. In
      addition, there was an extracellular cytoplasm canal between the cytoplasmic
      sheath and the flagellum. CONCLUSIONS: A principal components analysis explained
      the individual morphological variation fairly well. Of the total accumulated
      variance, 41.45% was accounted for by parameters related to the head and midpiece
      of the sperm and the length of the flagellum. Comparing the present study with
      previous studies of morphology of sturgeon spermatozoa, there were large inter-
      or intra-specific differences that could be valuable taxonomically.

PMID- 17014421
TI  - Renal sodium handling in patients with normal pressure glaucoma.
AB  - Low BP (blood pressure) is a recognized risk factor for some patients with NPG
      (normal pressure glaucoma). We have shown previously that patients with
      orthostasis have impaired circadian renal handling of sodium, which may
      contribute to the low BP. Therefore the aim of the present study was to examine
      the renal handling of sodium, the circadian variations in BP and the
      neurohormonal response to an orthostatic test in a selected subpopulation of 18
      patients with NPG with vasospastic and orthostatic symptoms, and in 24 healthy
      control subjects. The variations in BP and renal tubular sodium handling were
      evaluated using 24 h ambulatory BP recordings, 24 h urine collections and
      determination of endogenous lithium clearance as a marker of proximal sodium
      reabsorption. The neurohormonal and BP responses to changes in posture were also
      determined in a 30 min orthostatic test. This selected group of patients with NPG
      had lower 24 h ambulatory BPs (P<0.001), and a more pronounced fall in BP when
      assuming an upright position (P<0.001) compared with controls. FE(Li) (fractional
      excretion of lithium) was higher in patients with NPG than controls during the
      day (36.6+/-21.8 compared with 20.4+/-8.7% respectively; P<0.01; values are
      means+/-S.D.) as well as during the night (38.8+/-41.9 compared with 19.7+/-10.8%
      respectively; P<0.02), suggesting a reduced reabsorption of sodium in the
      proximal tubule. This was compensated for by an increased distal reabsorption of
      sodium in patients with NPG (P<0.01). These data demonstrate that patients with
      vasospastic NPG have a high excretion of lithium, suggesting reduced sodium
      reabsorption in the proximal tubule, in spite of a low BP. The abnormal renal
      sodium handling might contribute to the maintenance of arterial hypotension and
      progression of the optic nerve damage in these patients.

PMID- 17014422
TI  - The regulation of ATF3 gene expression by mitogen-activated protein kinases.
AB  - ATF3 (activating transcription factor 3) gene encodes a member of the ATF/CREB
      (cAMP-response-element-binding protein) family of transcription factors. Its
      expression is induced by a wide range of signals, including stress signals and
      signals that promote cell proliferation and motility. Thus the ATF3 gene can be
      characterized as an 'adaptive response' gene for the cells to cope with extra-
      and/or intra-cellular changes. In the present study, we demonstrate that the p38
      signalling pathway is involved in the induction of ATF3 by stress signals.
      Ectopic expression of CA (constitutively active) MKK6 [MAPK (mitogen-activated
      protein kinase) kinase 6], a kinase upstream of p38, indicated that activation of
      the p38 pathway is sufficient to induce the expression of the ATF3 gene.
      Inhibition of the pathway indicated that the p38 pathway is necessary for various
      signals to induce ATF3, including anisomycin, IL-1beta (interleukin 1beta),
      TNFalpha (tumour necrosis factor alpha) and H2O2. Analysis of the endogenous ATF3
      gene indicates that the regulation is at least in part at the transcription
      level. Specifically, CREB, a transcription factor known to be phosphorylated by
      p38, plays a role in this induction. Interestingly, the ERK (extracellular-signal
      regulated kinase) and JNK (c-Jun N-terminal kinase)/SAPK (stress-activated
      protein kinase) signalling pathways are neither necessary nor sufficient to
      induce ATF3 in the anisomycin stress paradigm. Furthermore, analysis of caspase 3
      activation indicated that knocking down ATF3 reduced the ability of MKK6(CA) to
      exert its pro-apoptotic effect. Taken together, our results indicate that a major
      signalling pathway, the p38 pathway, plays a critical role in the induction of
      ATF3 by stress signals, and that ATF3 is functionally important to mediate the
      pro-apoptotic effects of p38.

PMID- 17014423
TI  - Determination of the external loops and the cellular orientation of the N- and
      the C-termini of the human organic anion transporter hOAT1.
AB  - The OAT (organic anion transporter) family mediates the absorption, distribution
      and excretion of a diverse array of environmental toxins and clinically important
      drugs. OAT dysfunction significantly contributes to renal, hepatic, neurological
      and fetal toxicity and disease. As a first step to establish the topological
      model of hOAT1 (human OAT1), we investigated the external loops and the cellular
      orientation of the N- and the C-termini of this transporter. Combined approaches
      of immunofluorescence studies and site-directed chemical labelling were used for
      such purpose. Immunofluorescence microscopy of Myc-tagged hOAT1 expressed in
      cultured cells identified that both the N- and the C-termini of the transporter
      were located in the cytoplasm. Replacement of Lys59 in the predicted
      extracellular loop I with arginine resulted in a mutant (K59R), which was largely
      inaccessible for labelling by membrane-impermeable NHS (N-hydroxysuccinimido)-SS
      (dithio)-biotin present in the extracellular medium. This result suggests that
      loop I faces outside of the cell membrane. A single lysine residue introduced
      into putative extracellular loops III, V and VI of mutant K59R, which is devoid
      of extracellular lysine, reacted readily with membrane-impermeable NHS-SS-biotin,
      suggesting that these putative extracellular loops are in the extracellular
      domains of the protein. These studies provided the first experimental evidence on
      the extracellular loops and the cellular orientation of the N- and the C-termini
      of hOAT1.

PMID- 17014424
TI  - Degradation of extracellular matrix and its components by hypobromous acid.
AB  - EPO (eosinophil peroxidase) and MPO (myeloperoxidase) are highly basic haem
      enzymes that can catalyse the production of HOBr (hypobromous acid). They are
      released extracellularly by activated leucocytes and their binding to the
      polyanionic glycosa-minoglycan components of extracellular matrix (proteoglycans
      and hyaluronan) may localize the production of HOBr to these materials. It is
      shown in the present paper that the reaction of HOBr with glycosaminoglycans
      (heparan sulfate, heparin, chondroitin sulfate and hyaluronan) generates polymer
      derived N-bromo derivatives (bromamines, dibromamines, N-bromosulfon-amides and
      bromamides). Decomposition of these species, which can occur spontaneously and/or
      via one-electron reduction by low-valent transition metal ions (Cu+ and Fe2+),
      results in polymer fragmentation and modification. One-electron reduction of the
      N-bromo derivatives generates radicals that have been detected by EPR spin
      trapping. The species detected are consistent with metal ion-dependent polymer
      fragmentation and modification being initiated by the formation of nitrogen
      centred (aminyl, N-bromoaminyl, sulfonamidyl and amidyl) radicals. Previous
      studies have shown that the reaction of HOBr with proteins generates N-bromo
      derivatives and results in fragmentation of the polypeptide backbone. The
      reaction of HOBr with extracellular matrix synthesized by smooth muscle cells in
      vitro induces the release of carbohydrate and protein components in a time
      dependent manner, which is consistent with fragmentation of these materials via
      the formation of N-bromo derivatives. The degradation of extracellular matrix
      glycosaminoglycans and proteins by HOBr may contribute to tissue damage
      associated with inflammatory diseases such as asthma.

PMID- 17014425
TI  - Enhancement of tanshinone production in Salvia miltiorrhiza Bunge (red or Chinese
      sage) hairy-root culture by hyperosmotic stress and yeast elicitor.
AB  - The present study evaluates the use of hyperosmotic stress and a biotic elicitor
      YE (yeast elicitor; polysaccharide fraction of yeast extract) to stimulate
      diterpenoid tanshinone production in hairy-root culture of Salvia miltiorrhiza
      Bunge (Lamiaceae). Sorbitol was applied as an osmoticum at various concentrations
      (30-100 g/l) to the hairy-root culture in MS (Murashige and Skoog) medium
      [Murashige and Skoog (1962) Physiol. Plant. 15, 473-497] containing 30 g/l
      sucrose, and it increased the TT (total tanshinone) content of roots most
      dramatically at 50-70 g/l (medium osmolality 410-500 mmol/kg; 1 mol/kg
      approximately 1 osmol/kg), to 4.5-fold of that in the control. The hairy roots
      showed strong tolerance to hyperosmotic stress, retaining a stable or higher dry
      weight of roots at osmolality up to 500 mmol/kg. Most remarkably, the combined
      use of sorbitol (50 g/l) and YE (100 mg/l) increased the TT content 10-fold
      (1481.6 versus 146.4 microg/g dry root) and the volumetric tanshinone yield 9
      fold (16.3 versus 1.77 mg/l) compared with the control. The results suggest that
      the combined use of hyperosmotic stress and a biotic elicitor can effectively
      enhance secondary metabolite production in hairy-root cultures.

PMID- 17014426
TI  - The toxofilin-actin-PP2C complex of Toxoplasma: identification of interacting
      domains.
AB  - Toxofilin is a 27 kDa protein isolated from the human protozoan parasite
      Toxoplasma gondii, which causes toxoplasmosis. Toxofilin binds to G-actin, and in
      vitro studies have shown that it controls elongation of actin filaments by
      sequestering actin monomers. Toxofilin affinity for G-actin is controlled by the
      phosphorylation status of its Ser53, which depends on the activities of a casein
      kinase II and a type 2C serine/threonine phosphatase (PP2C). To get insights into
      the functional properties of toxofilin, we undertook a structure-function
      analysis of the protein using a combination of biochemical techniques. We
      identified a domain that was sufficient to sequester G-actin and that contains
      three peptide sequences selectively binding to G-actin. Two of these sequences
      are similar to sequences present in several G- and F-actin-binding proteins,
      while the third appears to be specific to toxofilin. Additionally, we identified
      two toxofilin domains that interact with PP2C, one of which contains the Ser53
      substrate. In addition to characterizing the interacting domains of toxofilin
      with its partners, the present study also provides information on an in vivo
      based approach to selectively and competitively disrupt the protein-protein
      interactions that are important to parasite motility.

PMID- 17014427
TI  - The gut microbiota: a complex ecosystem.

PMID- 17014428
TI  - Evaluation of the effects of probiotic supplementation from the neonatal period
      on innate immune development in infancy.
AB  - BACKGROUND: Activation of the innate immune system by microbial stimulation is
      believed to be critical for normal immune maturation, and there has been
      speculation that these pathways are important for inhibiting allergic-immune
      responses. OBJECTIVE: To assess innate immune function following a 6-month
      supplementation with probiotic bacteria. METHODS: Two hundred and thirty-one
      allergic, pregnant women were recruited into a randomized, controlled trial. The
      infants received either a probiotic (Lactobacillus acidophilus LAVRI-A1;
      Probiomics) or placebo (maltodextrin alone) daily for the first 6 months of life.
      Mononuclear cell samples were available from 118 infants. Functional responses to
      toll-like receptor (TLR) were assessed using ligands for TLR2 (Pansorbin) and
      TLR4/CD14 [lipopolysaccharide (LPS)] and measuring cytokine responses in the
      supernatants. Antigen-presenting cell function, as well as capacity for cytokine
      production (IL-12p70 and IL-10) was assessed. RESULTS: Infants in the probiotic
      group did not demonstrate differences in innate immune function compared with
      those in the control group. No differences were seen when cytokine responses were
      examined following stimulation with Pansorbin (TLR2) or LPS (TLR4). Similarly, no
      differences were seen in the antigen-presenting capacity of these infants. The
      mean fluorescence intensities of human leucocyte antigen-DR (HLA-DR) on
      monocytes, B cells and dendritic cells (DC) subsets were not affected, nor were
      the percentage of circulating DC subsets affected by a 6-month supplementation
      with L. acidophilus LAVRI-A1. CONCLUSIONS: Probiotic supplementation with L.
      acidophilus for the first 6 months of life did not alter early innate immune
      responses in this population at high risk of developing allergic disease.

PMID- 17014429
TI  - Effects of probiotic supplementation for the first 6 months of life on allergen-
      and vaccine-specific immune responses.
AB  - BACKGROUND: A reduction in microbial burden during infancy when allergen-specific
      memory is evolving has become a prominent explanation for the allergy epidemic.
      OBJECTIVE: We sought to determine whether probiotic dietary supplementation in
      the first 6 months of life could modify allergen- and vaccine-specific immune
      responses. METHODS: Two hundred and thirty-one pregnant women with a history of
      allergic disease and positive allergen skin prick test (SPT) were recruited into
      a randomized-controlled trial. The infants received either a probiotic (3 x
      10(9)Lactobacillus acidophilus LAVRI-A1; Probiomics) or placebo (maltodextrin
      alone) daily for the first 6 months of life, given independent of feeding
      methods. One hundred and seventy-eight children completed the study; blood
      samples were available from 60 children in the placebo group and 58 children in
      the probiotic group. Infant cytokine (IL-5, IL-6, IL-10, IL-13, TNF-alpha or TGF
      beta) responses to tetanus toxoid (TT), house dust mite (HDM), ovalbumin (OVA),
      beta-lactoglobulin (BLG), Staphylococcus enterotoxin B (SEB) and
      phytohaemaglutinin (PHA) were measured at 6 months of age. RESULTS: Children who
      received the probiotics showed reduced production of IL-5 and TGF-beta in
      response to polyclonal (SEB) stimulation (P=0.044 and 0.015, respectively). They
      also demonstrated significantly lower IL-10 responses to TT vaccine antigen
      compared with the placebo group (P=0.03), and this was not due to any differences
      in vaccination. However, there were no significant effects of probiotics on
      either Type 1 (Th1) or Type 2 (Th2) T helper cell responses to allergens or other
      stimuli. The only other effects observed were for reduced TNF-alpha and IL-10
      responsiveness to HDM allergens in children receiving probiotics (P=0.046 and
      0.014, respectively). CONCLUSIONS: In summary, although we did not see any
      consistent effects on allergen-specific responses, our study suggests that
      probiotics may have immunomodulatory effects on vaccine responses. The
      significance and clinical relevance of this need to be determined in further
      studies.

PMID- 17014430
TI  - Early exposure to dichlorodiphenyldichloroethylene, breastfeeding and asthma at
      age six.
AB  - Our aims were to assess association of dichlorodiphenyldichloroethylene (DDE)
      with childhood asthma measured up to age 6 and the effect of DDE on the
      protective effect of breastfeeding on asthma. In addition, we attempted to assess
      the relevant time-window of DDE exposure (i.e. at birth or at 4 years). All women
      presenting for antenatal care in Menorca, Spain over a 12-month period beginning
      in mid-1997 were invited to take part in a longitudinal study that included a
      yearly visit. Four hundred eighty-two children were enrolled and 462 provided
      complete outcome data after 6.5 years of follow-up. Organochlorine compounds were
      measured in cord serum of 402 (83%) infants and in blood samples of 285 children
      aged 4. We defined asthma as the presence of wheezing at age 6 and during any
      preceding year or doctor-diagnosed asthma, and used skin prick test at age 6 to
      determine atopic status. Results At birth and 4 years of age, all children had
      detectable levels of DDE (median 1 ng/mL and 0.8 ng/mL, respectively). From birth
      to age 4, the mean DDE level among children with artificial feeding decreased by
      72%, while among breastfed children it increased by 53%. Diagnosed asthma and
      persistent wheezing were associated with DDE at birth [odds ratio (OR) for an
      increase in 1 ng/mL, OR=1.18, 95% confidence interval (95% CI)=1.01-1.39 and
      OR=1.13, 95% CI=0.98-1.30, respectively], but not with DDE at 4 years. Neither
      breastfeeding nor atopy modified these associations (P>0.3). Breastfeeding
      protected against diagnosed asthma (OR=0.33, 95% CI=0.08-0.87) and wheezing
      (OR=0.53, 95% CI=0.34-0.82) in children with low and high DDE levels at birth.
      Conclusion In a community without known dichlorodiphenyltrichloroethane
      environmental releases, this study strengthens the evidence for an effect of DDE
      on asthma by measuring the disease at age 6 and does not support the hypothesis
      that DDE modifies the protective effect of breastfeeding on asthma.

PMID- 17014431
TI  - Early exposure to latex products mediates latex sensitization in spina bifida but
      not in other diseases with comparable latex exposure rates.
AB  - BACKGROUND: The high prevalence of latex sensitization in patients with spina
      bifida (SB) has been attributed to repeated and early exposure to latex products.
      Other diseases such as gastroschisis/omphalocoele and post
      haemorrhagic/congenital hydrocephalus are also associated with repeated and early
      latex exposure. OBJECTIVE: The aim of the study was to evaluate whether the high
      prevalence of latex sensitization in patients with SB is rather related to the
      underlying disease itself than to disease-associated known risk factors. METHODS:
      We compared children with SB (n=35), children with gastroschisis/omphalocoele
      (G/O, n=20) and children with post-haemorrhagic/congenital hydrocephalus (PH,
      n=45). All children with SB and PH had a ventriculo-peritoneal shunt since a very
      young age. Patients who underwent three or less surgical procedures matched in
      terms of age, number of operations, atopy and gender distribution, and were
      analysed for IgE sensitization rates to latex. RESULTS: In the SB group, 16 of 35
      patients (46%) showed elevated latex-specific IgE antibodies in contrast to one
      of 20 patients (5%) in the G/O group and four of 45 patients (8.9%) in the PH
      group (P<0.0005 and P<0.005, Fisher's exact test). Comparing matched control
      groups (<or=3 operations), the effects remained significant (P<0.05 and P<0.01).
      CONCLUSION: This study suggests that the SB population bears a disease-associated
      propensity for latex sensitization. This effect cannot be explained exclusively
      by a higher number of operations and differences related to atopy, age or gender.

PMID- 17014432
TI  - Association of TNF-alpha genetic polymorphism with HLA DPB1*0301.
AB  - BACKGROUND: We speculated TNF-alpha can be one of candidate gene for aspirin
      intolerant asthma (AIA) because TNF-alpha is pro-inflammatory cytokine and known
      to be increased level in asthmatic airways. In addition, genetic interaction
      between TNF-alpha and human antigen leucocyte (HLA) DPB1*0301, which is a strong
      genetic marker for AIA, was examined for its close location within chromosome 6.
      METHOD: To investigate genetic association of TNF-alpha with an AIA phenotype,
      three study groups (163 patients with AIA, 197 patients with aspirin-tolerant
      asthma (ATA), 257 normal control subjects) were enrolled. Single nucleotide
      polymorphisms (SNPs) were genotyped using a single-base extension method and HLA
      DPB1 genotyping was determined by high-throughput sequencing method. RESULTS: All
      five SNPs of TNF-alpha were tested; there were no significant differences in
      allele and genotype frequencies among the three groups. However, significant
      association between TNF-alpha-308G>A polymorphism and atopy status was noted
      (P<0.05). Gene to gene interaction between TNF-alpha-1031T>C (or -863C>A or 
      857C>A) and HLA DPB1*0301could synergistically increase the susceptibility to AIA
      with odds ratio (OR) to 7.738 (or OR=8.184 for -863C>A, OR=7.500 for -857C>T,
      P<0.001, respectively). CONCLUSION: TNF-alpha promoter polymorphism may
      significantly increase susceptibility to AIA by gene-to-gene interaction with HLA
      DPB1*0301.

PMID- 17014433
TI  - The effect of endogenous nitric oxide on mechanical ciliostimulation of human
      nasal mucosa.
AB  - BACKGROUND: Endogenous nitric oxide (NO) production by the inducible NO-synthase
      is enhanced in the nasal respiratory epithelium of patients with allergic
      rhinitis. Recent experimental data suggest endogenous NO to be strongly involved
      in the regulation of ciliary activity, the driving force of the mucociliary
      transport system. OBJECTIVE: In this study, we investigated the effect of
      endogenous NO on mechanical stimulation of ciliary activity in a nasal mucosa
      explant model. METHODS: Cultures of nasal mucosa explants were incubated with TNF
      alpha and bacterial lipopolysaccharides (LPS) to enhance endogenous NO
      production. Direct in vitro NO imaging was performed by the fluorescent NO
      indicator DAF-2 DA and laser scanning confocal microscopy. Ciliary beat frequency
      (CBF) was determined using a photoelectric technique. Mechanical stimulation was
      performed by two consecutive flow increments in a closed perfusion chamber.
      Endogenous NO-synthesis was blocked by l-NAME before the second flow stimulation.
      RESULTS: Under control conditions the mean rise of CBF relative to baseline was
      30.2% during the first flow increment and 30.7% during the second flow increment.
      Blocking of the endogenous NO synthesis in TNF-alpha/LPS-stimulated cultures
      reduced baseline CBF by 10.6+/-2.1% (P<0.05) but the effect of mechanical
      ciliostimulation on CBF remained unchanged (36.0% vs. 38.2%). CONCLUSION: In
      conclusion, endogenous NO- and Ca(2+)-dependent mechanical stimulation of ciliary
      activity probably use independent intracellular signalling pathways. The
      combination of both effects on ciliary activity is likely to improve the local
      defence against inhaled allergens in patients with nasal allergies.

PMID- 17014434
TI  - Spatial expression of two anti-inflammatory mediators, annexin 1 and galectin-1,
      in nasal polyposis.
AB  - BACKGROUND: There is renewed interest in the role played by specific counter
      regulatory mechanisms to control the inflammatory host response, poorly
      investigated in human pathology. Here, we monitored the expression of two anti
      inflammatory mediators, annexin 1 and galectin-1, and assessed their potential
      link to glucocorticoids' (GCs) effective control of nasal polyposis (NP).
      METHODS: Total patterns of mRNA and protein expression were analysed by
      quantitative real-time PCR (qPCR) and Western blotting analyses, whereas
      ultrastructural immunocytochemistry was used for spatial localization and
      quantification of each mediator, focusing on mast cells, eosinophils and
      epithelial cells. RESULTS: Up-regulation of the annexin 1 gene, and down
      regulation of galectin-1 gene, was detected in polypoid tissue compared with
      nasal mucosa. Patient treatment with betamethasone augmented galectin-1 protein
      expression in polyps. At the cellular level, control mast cells and eosinophils
      displayed higher annexin 1 expression, whereas marked galectin-1 immunolabelling
      was detected in the granule matrix of mast cells. Cells of glandular duct
      epithelium also displayed expression of both annexin 1 and galectin-1, augmented
      after treatment. CONCLUSION: Mast cells and epithelial cells appeared to be
      pivotal cell types involved in the expression of both annexin 1 and galectin-1.
      It is possible that annexin 1 and galectin-1 could be functionally associated
      with a specific mechanism in NP and that GC exert at least part of their
      beneficial effects on the airway mucosa by up-regulating, in a specific cell
      target fashion, these anti-inflammatory agonists.

PMID- 17014435
TI  - Synergistic effects of fluticasone propionate and salmeterol on inhibiting
      rhinovirus-induced epithelial production of remodelling-associated growth
      factors.
AB  - BACKGROUND: Rhinoviruses (RV), the major trigger of acute asthma exacerbations,
      are able to infect bronchial epithelium and induce production of pro
      inflammatory, but also angiogenic and pro-fibrotic mediators. Fluticasone
      propionate (FP) and salmeterol (S) are clinically effective and act
      synergistically in controlling persistent asthma; however, their effect on virus
      associated asthma is less clear. AIM: The aim of this study was to assess the
      individual and combined effects of FP and S on RV-induced epithelial production
      of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF
      2). METHODS: Bronchial epithelial cells (BEAS-2B) were exposed in vitro to RV and
      were subsequently treated with FP and S, at physiologically relevant
      concentrations, alone or in combination. VEGF and FGF-2 were measured in the
      supernatants of these cultures using ELISA. RESULTS: FP was able to reduce RV
      induced VEGF production in a dose-dependent manner. S also induced a smaller
      reduction; addition of both factors inhibited VEGF synergistically. FGF-2
      production was not inhibited by either FP or S alone, but was significantly
      reduced when both substances were present in the culture. CONCLUSION: This study
      demonstrates that FP and S may synergistically inhibit the production of
      angiogenic and/or pro-fibrotic factors that are induced after RV infection of
      BEAS-2B and are implicated in airway remodelling, suggesting that this
      combination may represent an important therapeutic option on virus-induced
      asthma.

PMID- 17014436
TI  - Defining the T cell antigen proteome of wasp venom.
AB  - BACKGROUND: While modulation of T cell function is believed to be important in
      the successful acquisition of clinical tolerance during venom immunotherapy,
      little is known of the role of wasp venom specific T cell antigens. OBJECTIVE: We
      sought comprehensively to characterize the T cell proteome for wasp venom to
      facilitate the future development of T cell-based immunotherapeutic approaches.
      METHODS: Using peripheral blood mononuclear cells from wasp venom-allergic
      individuals and IL-4 ELISPOT analysis, we characterized T cell responses to whole
      venom and gel filtration/ion exchange-fractionated venom. Reactive fractions were
      purified and identified using highly sensitive electrospray ion-trap mass
      spectrometry. RESULTS: Wasp venom-allergic individuals have detectable whole wasp
      venom-specific T cells directly ex vivo, which show rapid IL-4 effector function.
      T cell responses to gel filtration/ion exchange fractionated venom were dominated
      by responses to phospholipase A(1), hyaluronidase and antigen 5. CONCLUSION:
      Although it is likely that there are many T cell antigens within wasp venom, the
      main responses are to proteins coincident with the known IgE-binding proteins.

PMID- 17014438
TI  - p-Phenylenediamine allergy: the role of Bandrowski's base.
AB  - p-Phenylenediamine (PPD) is a commonly used hair-dye and a potent skin allergen.
      The mechanism of sensitization is unknown, as PPD is protein unreactive. We
      studied Bandrowski's base (BB), a PPD trimer, as well as 1,4-benzoquinone (BQ), a
      PPD hapten. PPD patch-test positive patients were patch-tested to BB and BQ. All
      tests were negative to 0.01% BQ and 0.01% BB. Five of 14 (35.7%) tested had true
      positive reactions to 0.1% BQ. One percent BQ was found to be irritant. Seven of
      43 tested (16%) were positive to either 0.1% or 1% BB. The positive reactions to
      BB were weak, even when PPD reactions were strong. Mice lymph node assay gave EC3
      values of 0.14% for PPD compared with 0.03% for BB. Therefore, BB is
      approximately 10 times more potent than PPD, taking into account the molarity. We
      suggest that while PPD may act as a prohapten, there is probably a spectrum of
      antigenic determinants in vivo. BB may be bound or metabolized by keratinocytes
      before it reacts with Langerhans cells.

PMID- 17014437
TI  - Gastro-duodenal digestion products of the major peanut allergen Ara h 1 retain an
      allergenic potential.
AB  - BACKGROUND: The process of gastro-duodenal digestion may play a role in
      determining the allergenic properties of food proteins. The sensitizing and
      allergenic potential of digestion products of highly degraded allergens, such as
      the major peanut allergen Ara h 1, is currently under debate. We evaluated the
      effect of in vitro gastro-duodenal digestion of Ara h 1 on T cell reactivity and
      basophil histamine release. METHODS: An in vitro model of gastro-duodenal
      digestion was used to investigate changes in the allergenic properties of Ara h 1
      using in vitro assays monitoring T cell reactivity (proliferation, cytokine
      production) and histamine release of basophils from peanut allergic individuals.
      The digestion process was monitored using an SDS-PAGE gel. RESULTS: In vitro
      gastric digestion led to rapid degradation of Ara h 1 into small fragments M(r)
      L5600. Gastric digestion did not affect the ability of Ara h 1 to stimulate
      cellular proliferation. Gastro-duodenal digestion significantly reduced its
      ability to stimulate clonal expansion (P<0,05; Wilxocon's signed rank test). The
      Th-2 type cytokine polarization of T cells from peanut allergic donors (IFN
      gamma/IL-13 ratio and IFN-gamma/IL-4 ratio of CFSE(low) CD4(+) T cells) remained
      unchanged regardless of the level of digestion. Histamine release of basophils
      from peanut allergic individuals was induced to the same extent by native Ara h 1
      and its digestion products. CONCLUSION: Gastro-duodenal digestion fragments of
      Ara h 1 retain T cell stimulatory and IgE-binding and cross-linking properties of
      the intact protein.

PMID- 17014439
TI  - Role of intercellular adhesion molecule-1 in a murine model of toluene
      diisocyanate-induced asthma.
AB  - BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1)
      are thought to contribute to the airway inflammation and airway hyper
      responsiveness (AHR) of allergic asthma. Some differences from allergic asthma
      have been noted, including airway neutrophilia, and the involvement of ICAM-1 in
      toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized
      mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in
      airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice
      (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution
      or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed
      24 h after challenge by TDI or solvent. The production of antigen-specific IgG
      and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI
      challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell
      numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein
      2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All
      these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels
      of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable.
      CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway
      inflammation and AHR in TDI-induced asthma.

PMID- 17014440
TI  - cDNA cloning and substrate specificity of equine tryptase, a possible mediator in
      equine heaves.
AB  - BACKGROUND: Mast cell mediators are believed to play a central role in
      inflammatory lung disorders such as human allergic and occupational asthma.
      Equine heaves is characterized by reversible neutrophilic airway inflammation and
      airway obstruction, primarily due to bronchospasm and mucus hypersecretion,
      following exposure of susceptible horses to organic stable dusts. As such, heaves
      shares many similarities with human occupational dust-induced asthma and
      therefore it is proposed that mast cells may also be implicated in the
      pathogenesis of heaves. Tryptase, a mast cell-specific proteinase, can be used as
      an indicator of biological mast cell activity. OBJECTIVE: The aim of this study
      was to determine the cDNA sequence of equine tryptase and to investigate its
      substrate specificity in order to rationalize its enzymatic activity. METHODS: RT
      PCR cloning was used to sequence equine tryptase. Substrate specificity of equine
      tryptase was investigated using arginine and lysine containing substrates.
      RESULTS: The cDNA and deduced amino acid (Aa) sequences for equine tryptase
      shared strong identity with other tryptases. Unusually for a trypsin-like
      proteinase however, equine tryptase has alanine at residue 216, rather than
      glycine, which confers increased arginine substrate specificity in vitro and may
      restrict fibrinogenolysis in vivo. CONCLUSION: Cloning and sequencing of the mast
      cell proteinase equine tryptase will allow molecular probing of its expression in
      the lung of control and heaves-affected horses. Further work is warranted to
      determine the biological relevance of the unique alanine 216 substitution in the
      molecular sequence of the equine tryptase substrate-binding pocket.

PMID- 17014443
TI  - Montelukast in allergic rhinitis: a systematic review and meta-analysis.
AB  - Allergic rhinitis is common. This systematic review outlines the evidence
      regarding montelukast in allergic rhinitis and provides a meta-analysis of its
      efficacy. The evidence suggests that montelukast does reduce nasal symptom score
      by 3.4% (95% CI: 2.5% to 4.2%) when compared with placebo. Montelukast is not as
      effective as topical nasal steroids or antihistamines and should therefore be
      regarded as second line therapy. When used, montelukast should be used in
      combination with an antihistamine.

PMID- 17014444
TI  - Anatomical and surgical considerations of the external branch of the superior
      laryngeal nerve: a systematic review.
AB  - The anatomical course of the external branch of the superior laryngeal nerve
      (EBSLN) is variable, and a consistent approach to its preservation during thyroid
      surgery is needed to reduce risk of post-operative voice impairment. Despite
      agreement that careful dissection in the region of the superior thyroid pole is
      required, there is no accepted 'best' approach, nor any universal acknowledgement
      that location of the EBSLN is actually necessary. The popular cernea
      classification of EBSLN has limitations, including its decreased reliability with
      increased thyroid size and its irrelevance in cases of 'buried' variants. *
      Recent work has identified factors such as ethnicity and stature in the
      prevalence of EBSLN variants. Consistent approaches to the post-operative
      detection of EBSLN injury are needed to build an accurate picture of the
      incidence of surgical nerve injury. Then a standardised approach to EBSLN
      preservation may emerge.

PMID- 17014445
TI  - A comparison of endoscopic and microscopic removal of wax: a randomised clinical
      trial.
AB  - OBJECTIVES: Using a microscope to achieve a view of the canal during dewaxing is
      the most commonly performed method of dewaxing in secondary care, but an
      endoscope can also be used. We set out to compare endoscopic and microscopic
      dewaxing. DESIGN: Randomised clinical trial. SETTING: Otolaryngology Outpatient
      Department. PARTICIPANTS: One hundred participants selected sequentially from
      patients requiring dewaxing of their ears to allow examination of the tympanic
      membrane. Patients with external or middle ear pathology were excluded. METHODS:
      Patients were randomly assigned to have dewaxing performed using microinstruments
      aided by vision with a microscope or an endoscope. All participants who were
      entered the study completed the study. MAIN OUTCOME MEASURES: Levels of pain and
      discomfort experienced by the participants were assessed by a visual analogue
      scale (VAS). Difficulty of performing the dewaxing indicated by the endoscopist
      using a VAS. The length of time taken to perform the dewaxing was also recorded.
      RESULTS: Endoscopic dewaxing was less uncomfortable than microscopic dewaxing for
      patients (VAS median values 5 and 25 respectively; P < 0.002) as well as less
      painful (VAS median values 3.5 and 10 respectively; P < 0.075). Endoscopic
      dewaxing was easier to perform than microscopic dewaxing (VAS median values for
      difficulty were 9 and 20 respectively; P < 0.005) and took less time (mean time
      for endoscopic dewaxing was 1.8 min versus 3.3 min for microscopic dewaxing (P <
      0.001). Ninety-one per cent of ears could be dewaxed with a Jobson-Horne probe or
      wax hook. CONCLUSIONS: The cost of an operating microscope suitable for use with
      dewaxing is approximately 10 times that of a suitable endoscope, dewaxing is a
      cheaper alternative to microscopic dewaxing that has benefits for the patient and
      clinician.

PMID- 17014446
TI  - A single-blinded case controlled study on effects of cardiopulmonary circulation
      on hearing during coronary artery bypass grafting.
AB  - OBJECTIVES: To evaluate the effect of extra-corporeal (cardiopulmonary) bypass on
      hearing during coronary artery bypass grafting. DESIGN: Prospective (single
      blinded) controlled study. SETTING: District General Hospital. PARTICIPANTS:
      Fifty-two patients undergoing coronary artery bypass grafting completed this
      study. Comparison was made between 14 control patients undergoing off-pump
      coronary artery bypass grafting and 38 study patients undergoing on-pump coronary
      artery bypass grafting. The age range of patients was 48-81 years, with 50%
      between 64 and 66 years. MAIN OUTCOME MEASURES: Pure tone audiograms were
      performed in all patients before and after coronary artery bypass grafting. Data
      were analysed for any significant difference between pre- and post-operative pure
      tone audiograms. RESULTS: Mann-Whitney U-test demonstrated no difference between
      the area generated between mean pre- and post-operative audiograms (P = 0.754).
      No significant difference between off versus on pump was demonstrated for average
      differences at 250-500 Hz, 4 kHz, 4-8 kHz and 8 kHz. Wilcoxon matched-pairs
      signed-rank test demonstrated no difference between right and left ears for each
      individual frequency. Spearman's test to analyse the effect on vessel number or
      minutes on bypass pump revealed no significant difference at 4-8 kHz (P = 0.550
      for number of vessels and P = 0.276 for minutes on pump.) CONCLUSION: In this
      study, it was not possible to demonstrate any statistically significant
      deleterious effect of extra-corporeal (cardiopulmonary) bypass on hearing during
      coronary artery bypass grafting.

PMID- 17014447
TI  - Is admission for epistaxis more common in Caucasian than in Asian people? A
      preliminary study.
AB  - OBJECTIVES: Epistaxis is a common ENT complaint. Although casual observation
      suggested that it is more common in Caucasian, compared with Asian people, a
      literature search failed to find any studies investigating ethnicity and
      epistaxis. The aim of this study was to identify any differences in emergency
      admission rates for epistaxis between Asian and Caucasian people. DESIGN:
      Retrospective observational study using hospital computerised data (HISS).
      SETTING: Large University Hospital accepting ENT emergencies. PARTICIPANTS: All
      Asian and Caucasian patients admitted under ENT care as an emergency (1 January
      2000 to 30 November 2005), split into two groups: one composed of epistaxis
      patients, the other of all other ENT emergency admissions. MAIN OUTCOMES
      MEASURES: The proportions of Asian and Caucasian patients among the two patient
      groups, either epistaxis admissions or other ENT emergency admissions. RESULTS:
      The proportions of Asian and Caucasian patients in the group admitted with
      emergency epistaxis were 7.1% (100/1410) and 92.9% (1310/1410) respectively.
      However, the proportions of Asian and Caucasian patients in the group composed of
      any other ENT emergency were 13.2% (729/5515) and 86.8% (4786/5515), respectively
      (chi-squared P < 0.01). CONCLUSIONS: Caucasian people form an unexpectedly large,
      and Asians a smaller proportion of emergency epistaxis admissions. The
      possibility of an ethnic risk factor for epistaxis warrants further
      investigation.

PMID- 17014449
TI  - Quality of life assessment after non-laser endonasal dacryocystorhinostomy.
AB  - OBJECTIVE: There has been a lack of patient-centred evidence in the
      Otolaryngology literature, that non-laser endonasal dacryocystorhinostomy
      improves the quality of life of patients. Many studies demonstrate successful
      outcomes based on non-validated subjective patient reporting. The aim of this
      survey was to evaluate the impact of non-laser endonasal dacryocystorhinostomy on
      the quality of life of patients using a validated questionnaire, the Glasgow
      Benefit Inventory (GBI). DESIGN: Prospective non-randomised case series. SETTING:
      Secondary otorhinolaryngology-ophthalmology centre, single centre. PARTICIPANTS:
      Sixty-five consecutive patients undergoing non-laser endonasal
      dacryocystorhinostomy were asked to complete a questionnaire at their follow-up
      clinic appointment. All patients had a minimum of 9 months follow-up. MAIN
      OUTCOME MEASURES: A consultant ophthalmologist reviewed each patient six months
      after surgery and recorded the outcomes as 'cure', 'better', 'no change' or
      'worse'. We defined 'success' as cured or better. 'Failure' suggests no
      improvement or worsening epiphora. The validated 18-item GBI was used. RESULTS:
      Fully completed questionnaires were received from 55 patients. Mean total GBI
      scores were +34 for successful non-laser endonasal dacryocystorhinostomy and -19
      for failed non-laser endonasal dacryocystorhinostomy (Mann-Whitney z = 3.8, P <
      0.001). CONCLUSION: Successful non-laser endonasal dacryocystorhinostomy does
      confer significant quality of life improvement.

PMID- 17014448
TI  - The national comparative audit of surgery for nasal polyposis and chronic
      rhinosinusitis.
AB  - OBJECTIVES: This study summarises the results of a National Audit of sino-nasal
      surgery carried out in England and Wales. It describes patient and operative
      characteristics as well as patient outcomes up to 36 months after surgery.
      DESIGN: Prospective cohort study. SETTING: NHS hospitals in England and Wales.
      PARTICIPANTS: Consecutive patients undergoing surgery for nasal polyposis and/or
      chronic rhinosinusitis. MAIN OUTCOME MEASURE: The total score derived from a 22
      item version of the Sino-Nasal Outcome Test (SNOT-22). Lower scores represent
      better health-related quality of life. RESULTS: A total of 3128 consecutive
      patients at 87 NHS hospitals were enrolled. There is a large improvement in SNOT
      22 scores from the pre-operative period (mean = 42.0) to 3 months after surgery
      (mean = 25.5). The scores for patients undergoing nasal polypectomy improved from
      41.0 before surgery to 23.1 at 3 months after surgery, while the scores for
      patients undergoing surgery for chronic rhinosinusitis alone improved from 44.2
      to 31.2. The SNOT-22 scores reported at 12 and 36 months after surgery were
      similar to those reported at 3 months. Excessive bleeding occurred in 5% of
      patients during the operation and in 1% of patients after the operation. Intra
      orbital complications were reported in 0.2%. Of those patients undergoing primary
      surgery for bilateral grade I or II polyposis, 18% had not received a pre
      operative course of steroid treatment. At the 36-month follow-up, 11.4% of
      patients had undergone revision surgery. CONCLUSIONS: The audit confirms that
      sino-nasal surgery is generally safe and effective. There is some evidence that
      patient selection for surgery could be improved.

PMID- 17014450
TI  - Validation of a voice prosthesis questionnaire to assess valved speech and its
      related issues in patients following total laryngectomy.
AB  - OBJECTIVES: To establish the reliability and validity of a new self-administered
      questionnaire to assess valved speech and its related issues in patients who have
      undergone a total laryngectomy operation. DESIGN: Cross-sectional psychometric
      validation study. SETTING: Tertiary cancer care centre. PATIENTS: We identified
      sixty-one total laryngectomy patients with no sign of recurrent disease and using
      voice prosthesis from the speech and language therapy database of the Royal
      Marsden Hospital. The patients were assessed using a postal self-administered
      voice prosthesis questionnaire concerning the voice valve and it's related
      issues. Patients were also asked to complete the University of Michigan voice
      related quality of life and University of Washington head and neck quality of
      life (version 4) questionnaires. MAIN OUTCOME MEASURES: Test-retest and internal
      consistency reliability; content; criterion and construct validity. RESULTS: We
      received completed questionnaires from fifty-one of the sixty-one total
      laryngectomy patients identified for the study providing a response rate of 84%.
      The median age of the group was 65 years (range: 40-85) with thirty-seven males
      and fourteen females. The internal consistency reliability using the Cronbach's
      alpha coefficient was 0.87 (range: 0.85 to 0.89). Test-retest reliability showed
      that more than 75% of patients had a score on re-test that was within 1 point of
      their original score. Content validity was ensured during the design process. The
      median Spearman correlation coefficient was 0.25 for convergent construct
      validity with the University of Washington head and neck quality of life
      questionnaire and 0.64 for criterion validity on comparison with the University
      of Michigan voice related quality of life scale. CONCLUSIONS: The voice
      prosthesis questionnaire is the first validated and reliable self-administered
      questionnaire designed specifically for evaluating valved speech and its related
      issues in patients who have undergone total laryngectomy. The voice prosthesis
      questionnaire has significant utility for audit, outcomes research and monitoring
      in this unique group of patients.

PMID- 17014451
TI  - Exploring the relationship between severity of dysphonia and voice-related
      quality of life.
AB  - OBJECTIVES: To explore whether severity and/or consistency of dysphonia are
      linked to voice-related quality of life. DESIGN: Cross-sectional study. SETTING:
      Specialist voice clinics, University Teaching Hospital. PARTICIPANTS: Sixty adult
      patients attending with a primary complaint of dysphonia. Exclusion criteria were
      those below 16 years of age, transexual patients and those with a persistent
      dysphonia of >2 years. MAIN OUTCOME MEASURES: Voice-related quality of life as
      assessed by VoiSS. EXPLANATORY FACTORS: Severity of dysphonia as judged by
      perceptual ratings of voice (GRBAS); a visual analogue scale to judge best, worst
      and today's voice. RESULTS: There was a highly significant correlation between
      perceptual dysphonia severity as assessed by GRBAS and the total, impairment and
      emotional subsets of the VoiSS questionnaire (r from 0.48 to 0.64). There was a
      similar and highly significant correlation between best, worst and today's self
      rated voice and the total, impairment and emotional subsets of the VoiSS
      questionnaire (r from -0.40 to -0.60). However, none of the self-rated parameters
      was demonstrably better at explaining the effect on quality of life. CONCLUSIONS:
      An increasingly negative effect on quality of life appears to be associated with
      an increase in the severity of dysphonia. Further research on the role of quality
      of life measures in the assessment and treatment of dysphonia would be of value.

PMID- 17014452
TI  - Defining the stenotic post-laryngectomy tracheostoma and its impact on the
      quality of life in laryngectomees: development and validation of a stoma function
      questionnaire.
AB  - OBJECTIVES: The aims of this study were to identify if: (i) size of stoma
      contributes to quality of life (QoL) in laryngectomees; (ii) stoma size has an
      impact on routine stoma care and function; and (iii) an optimal stoma size exists
      below which patients experience stoma problems. DESIGN: Cross-sectional study of
      laryngectomees. SETTING: Two tertiary care centres. PARTICIPANTS: Fifty-seven
      patients who had undergone total laryngectomy one to five years ago and using
      tracheo-oesophageal speech as their primary communication means. MAIN OUTCOMES
      MEASURES: Three main measures were studied: 1 a new study specific questionnaire
      designed to assess problems with function and care of the end tracheosto- ma; 2
      QoL as assessed by the head and neck QoL instrument; 3 a precision custom
      designed sizer to measure the minimum stoma diameter. RESULTS: The final study
      specific questionnaire contained four items assessing different aspects of stomal
      function. From raw total scores an overall stomal score was generated. The stoma
      score was moderately correlated to emotion and speech domains in head and neck
      Quality of Life questionnaire, indicating that different concepts were being
      measured. The mean minimum stoma diameter was 15.9 +/- 2.9 mm. There was a
      significant increase in the area under the receiver operating characteristic
      curve beyond a threshold value of > or 15 mm; smaller sizes were associated with
      a poorer stoma score (Mann-Whitney test, P < 0.001). No patient found the stoma
      sizer use distressing. CONCLUSIONS: Size of stoma significantly contributes to
      QoL in laryngectomees and stomas with minimum diameters of 14 mm or less are
      associated with adverse effects on routine stoma function. The study-specific
      stoma function questionnaire appears to be a useful instrument.

PMID- 17014453
TI  - Fibreoptic endoscopic evaluation of swallowing and videofluoroscopy: does
      examination type influence perception of pharyngeal residue severity?
AB  - OBJECTIVES: The aim of the study was to investigate whether the type of
      instrumental swallowing examination (Fibreoptic Endoscopic Evaluation of
      Swallowing (FEES) or videofluoroscopy) influences perception of post-swallow
      pharyngeal residue. DESIGN: Prospective, single-blind assessment of residue from
      simultaneous videofluoroscopy and FEES recordings. All raters were blind to
      participant details, to the pairing of the videofluoroscopy and FEES examinations
      and to the other raters' scores. SETTING: Tertiary specialist ENT teaching
      hospital. PARTICIPANTS: Fifteen adult participants consecutively recruited; seven
      women and eight men aged between 22 and 73, mean age 53. All participants
      underwent one FEES examination and one videofluoroscopy examination performed
      simultaneously. INCLUSION CRITERIA: referred to speech and language therapy for
      assessment of dysphagia. EXCLUSION CRITERIA: nil by mouth or judged to be at high
      risk of aspiration. MAIN OUTCOME MEASURES: The FEES and videofluoroscopy
      examinations were recorded simultaneously. Fifteen speech and language therapists
      independently scored pharyngeal residue as none, coating, mild, moderate or
      severe. All examinations were scored twice by all raters. RESULTS: Intra- and
      inter-rater agreement were similar for both examinations. There were significant
      differences between FEES and videofluoroscopy pharyngeal residue severity scores
      (anova, P < 0.001). FEES residue scores were consistently higher than
      videofluoroscopy residue scores. CONCLUSIONS: Pharyngeal residue was consistently
      perceived to be greater from FEES than from videofluoroscopy. These findings have
      significant clinical implications as FEES and videofluoroscopy findings are used
      to judge aspiration risk and to make recommendations for oral intake. Further
      research is required to examine the impact of FEES and videofluoroscopy
      examinations on treatment decisions.

PMID- 17014454
TI  - A child with cervical lymphadenopathy.

PMID- 17014457
TI  - How we do it: The Dutch functional hearing-screening tests by telephone and
      internet.
AB  - Keypoints * The Dutch National Hearing Test is a reliable and very successful
      functional hearing-screening test by telephone. An internet version of the
      National Hearing Test was also implemented. * The National Hearing Test is a
      fully automatic adaptive speech-in-noise test that uses digit-triplets as speech
      material. The result of the test is given as 'good,''insufficient,' or 'poor.' *
      The test by telephone performs better in reaching older subjects, who are more
      likely to suffer from hearing loss, than the test by internet. * More than 50% of
      the participants who scored 'insufficient' or 'poor' followed the recommendation
      to visit a GP, hearing-aid dispenser, ENT specialist or Audiological Center. *
      The tests contribute to increase the identification and treatment of older
      hearing-impaired subjects.

PMID- 17014459
TI  - How we do it: Changes in thyroid and salivary gland surgery since 1989: who's
      doing it and what are they doing?
AB  - Keypoints * The aim of this study was to identify changes in the provision of
      parotid, submandibular and thyroid gland surgery between surgical specialties
      since 1989, as well as changes in surgical practice. * Data from the Department
      of Health's Hospital Episode Statistics (HES) was extracted from 1989/1990 and
      2003/2004 records by operation and surgical specialty in England. * The data
      reveals a considerable decline in the amount of parotid and submandibular surgery
      performed by General surgeons; with the majority of this surgery currently being
      performed by ENT surgeons, and to a lesser extent, Oral and Maxillo-Facial
      surgeons. * Thyroid surgery has undergone less radical change, with General
      surgeons continuing to perform the majority of cases; however, an increasing
      proportion is now provided by ENT surgeons. * There also seems to be changes in
      the types of thyroid operation being performed; with large increases in total
      thyroidectomy and reductions in subtotal thyroidectomies.

PMID- 17014458
TI  - How we do it: Transoral suction diathermy adenoid ablation under direct vision
      using a 45 degree endoscope.
AB  - Keypoints * Adenoid ablation using suction diathermy is associated with a number
      of difficulties, mainly associated with the use of the mirror. Transoral and
      transnasal 0 degree endoscopes have also been utilised but again have
      limitations. We describe a technique that overcomes the above problems. * A
      prospective case series of patients undergoing suction diathermy adenoidectomy
      under direct vision using a transoral 45 degree endoscope connected to a monitor
      was conducted, performed by surgical trainees and under direct supervision of the
      consultant trainer (J.R.-J.). * Intra-operatively, trainees had to demonstrate to
      the trainer the appropriate anatomy, completed adenoid ablation, and haemostasis.
      * Fifty-six cases have been performed. In every case, it was possible for the
      trainer to monitor the trainee's technique throughout the entire procedure. No
      complications have been reported. * We describe a modified technique which
      overcomes the disadvantages previously encountered by conventional suction
      diathermy adenoid ablation.

PMID- 17014460
TI  - How we do it: Chemo-electroporation in the head and neck for otherwise
      untreatable patients.
AB  - Keypoints * Chemo-electroporation therapy with bleomycin is a locoregional
      treatment modality for head and neck and skin cancer, with the potential to
      preserve function. * In our institution, chemo-electroporation therapy is used
      for patients that can no longer be treated by surgery or radiotherapy, or for
      whom surgical treatment would be very extensive and thus declined by the patient.
      * This paper describes in detail the technique of bleomycin-electroporation
      therapy. The literature is reviewed and preliminary results of the clinical trial
      are presented. * The main focus of the trial is to determine the safety,
      effectiveness, and burden of bleomycin-electroporation therapy for the patient. *
      All 17 tumours responded to therapy. Local tumour control was reached in 14 of
      the 17 (82.4 %) tumours. * Based on the outcome of the clinical trial, bleomycin
      electroporation therapy has the potential to become a valuable addition to the
      late-stage treatment options for patients with head and neck or skin tumours.

PMID- 17014461
TI  - How we do it: Dispensing with drains in hemithyroidectomy--a feasibility study.
AB  - Keypoints * The NHS plan states that 75% of all elective surgery should be
      carried out as day cases, but reports confirm that we are falling well below such
      targets. * The use of the harmonic scalpel in thyroidectomy in our department has
      facilitated faster surgery, minimal intra-operative haemorrhage, and reduced
      postoperative blood loss into the drain. * We propose that patients with small
      solitary nodules (<25 cm(3) on preoperative ultrasound) undergoing
      hemithyroidectomy for diagnostic purposes are candidates for selective use of
      drains, or where used, early removal of the drain and same day discharge.

PMID- 17014462
TI  - Double-blind randomised controlled study of coblation tonsillotomy versus
      coblation tonsillectomy on postoperative pain in children.

PMID- 17014463
TI  - Nasal catheter insertion for suction diathermy adenoidectomy: tip profile.

PMID- 17014467
TI  - Postoperative discharge advice - whose job is it?

PMID- 17014468
TI  - Graphic visual adaptation of House-Brackmann facial nerve grading for peripheral
      facial palsy: an alternative analysis of reliability.

PMID- 17014472
TI  - Randomised-controlled study comparing post-operative pain between coblation
      palatoplasty and laser palatoplasty.

PMID- 17014473
TI  - Semont's manoeuvre in BPPV: a forgotten technique.

PMID- 17014474
TI  - Is day case tonsillectomy achievable within the 'payment by results' policy in
      remote areas?

PMID- 17014475
TI  - Return to basics with Naseptin.

PMID- 17014476
TI  - Securing head and neck surgical drains made easy.

PMID- 17014477
TI  - Overcoming anosmia following total laryngectomy.

PMID- 17014480
TI  - Update on retinoid therapy of psoriasis in: an update on the use of retinoids in
      dermatology.
AB  - Both in the topical and systemic treatment of psoriasis, retinoids are mainstays.
      In this chapter the history and modes of actions of retinoids are presented.
      Tazarotene and acitretin are the only retinoids that are available in both
      topical and systemic formulations. A more extensive description of their
      pharmacology, modes of action, indications and contraindications, clinical
      results, and treatment strategies will be presented. Finally, retinoid X receptor
      ligands and retinoic acid metabolism blocking agents will be introduced as
      potential future retinoid mimetics in psoriasis.

PMID- 17014481
TI  - Treatment of cutaneous T-cell lymphoma with retinoids.
AB  - Retinoids are biologic regulators of differentiation, proliferation, apoptosis,
      and immune response. Retinoids (all-trans retinoic acid, 13-cis-retinoic acid,
      and the synthetic analogs isotretinoin, etretinate, and acitretin) have been used
      for years as monotherapy and/or in combination for treatment of cutaneous T-cell
      lymphomas (CTCL). Orally administered bexarotene, the first synthetic highly
      selective retinoid X receptor retinoid to be approved by the Food and Drug
      Administration for CTCL, was shown to be active against the cutaneous
      manifestations of all stages of CTCL. The topical gel formulation was also
      effective for early cutaneous manifestations of CTCL or as an adjunct to systemic
      or phototherapy. Use of retinoids in future long-term clinical trials and their
      eventual application in CTCL regiments will require strategies to decrease the
      side effects of existing retinoids, identify novel receptor subtype-selective
      retinoids with better therapeutic index, and explore biologically based
      synergistic combination therapies with other active agents.

PMID- 17014482
TI  - Update in retinoid therapy of acne.
AB  - The pathogenesis of acne, the most common skin disease, is complex and
      multifactorial. Clinical experience has demonstrated that parallel targeting of
      various pathogenetic factors, achieved either by mono- or combination therapy
      with appropriate drugs, represents the most effective approach to treating acne.
      Topical retinoids have been shown to expulse mature comedones, reduce
      microcomedone formation, and exert immunomodulatory effects. They have broad anti
      acne activity without the risk of inducing bacterial resistance, which justifies
      their use as first-line treatment in most types of noninflammatory and
      inflammatory acne and makes them uniquely suitable as long-term medication to
      maintain remission after cessation of initial combination therapy. Systemic
      isotretinoin as a monotherapeutic agent strongly affects all four major
      pathogenetic factors and has been, in the hand of experienced dermatologists, a
      potent and safe agent for the treatment of severe and recalcitrant acne forms for
      more that 20 years. However, patient counseling, careful monitoring, and
      evaluation and management of adverse events are necessary. The use of
      isotretinoin has experienced a drawback now that its indication has been lowered
      from a first-line to a second-line medication.

PMID- 17014483
TI  - Retinoid therapy of pigmentary disorders.
AB  - Topical retinoids such as all-trans-retinoic acid (RA), 13-cis-retinoic acid
      (isotretinoin), retinol, retinaldehyde, tazarotene, and adapalene have been shown
      to improve dyspigmentation of photodamaged skin including mottling and actinic
      lentigines. RA monotherapy has also been demonstrated to improve melasma and
      postinflammatory hypermelanosis. Furthermore, RA in combination with hydroquinone
      or 4-hydroxyanisole, or azelaic acid increases the potency of depigmenting agents
      for the treatment of melasma, actinic lentigines, and postinflammatory
      hypermelanosis. The basic mechanisms underlying these effects are not completely
      identified. Topical retinoids stimulate the cell turn-over of epidermal
      keratinocytes and promote a decrease in melanosome transfer and a rapid loss of
      melanins via epidermopoiesis. Topical retinoids are also involved in the control
      of cell differentiation. Retinoid-induced changes in the stratum corneum and the
      permeability barrier may also facilitate the penetration of depigmenting agents
      in the epidermis and increase their bioavailability, leading to increased
      depigmentation. In addition, several in vitro studies demonstrate that cis and
      trans-retinoic acid inhibit UV-B stimulated melanogenesis in term of tyrosinase
      activity and melanin synthesis. It is likely that topical retinoids modulate
      epidermal melanin count via a direct action on melanocytes and epidermal
      keratinocytes.

PMID- 17014484
TI  - Retinoids in cosmeceuticals.
AB  - Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic
      molecules and easily penetrate the epidermis. Their biologically active forms can
      modulate the expression of genes involved in cellular differentiation and
      proliferation. Retinoic acid (tretinoin), its 13-cis isomer isotretinoin, as well
      as various synthetic retinoids are used for therapeutic purposes, whereas
      retinaldehyde, retinol, and retinyl esters, because of their controlled
      conversion to retinoic acid or their direct receptor-independent biologic action,
      can be used as cosmeceuticals. These natural retinoic acid precursors are thus
      expected to be helpful in (i) renewing epidermal cells, (ii) acting as UV
      filters, (iii) preventing oxidative stress, (iv) controlling cutaneous bacterial
      flora, and (v) improving skin aging and photoaging. Retinol and retinyl esters
      are not irritant, whereas demonstrating only a modest clinical efficiency. On the
      other hand, retinaldehyde, which is fairly well tolerated, seems to be the most
      efficient cosmeceutical retinoid; it has significant efficiency toward oxidative
      stress, cutaneous bacterial flora, epidermis renewing, and photoaging.

PMID- 17014485
TI  - The use of retinoids in the treatment of photoaging.
AB  - Photoaging describes the clinical and histologic consequences of chronic sun
      exposure, the key features of which--wrinkles and mottled hyperpigmentation--are
      frequently and erroneously attributed to the aging process. Although a number of
      surgical procedures can improve the clinical appearance of photoaged skin, the
      only medical therapy with proved benefit derived from randomized clinical trial
      evidence is the use of topical retinoids, particularly tretinoin, isotretinoin,
      and tazarotene. Retinoids are capable not only of repairing photoaged skin at
      both the clinical and biochemical levels but their use may prevent photoaging.
      There is in addition emerging evidence that topical retinoids could be beneficial
      in the treatment of intrinsically aged skin.

PMID- 17014486
TI  - Skin cancer chemoprevention with systemic retinoids: an adjunct in the management
      of selected high-risk patients.
AB  - Systemic retinoids (isotretinoin, etretinate, and acitretin) have been shown to
      be effective chemotherapeutic agents in studies of patients with xeroderma
      pigmentosum, the nevoid basal cell carcinoma syndrome, and recipients of organ or
      bone marrow transplantation. In addition, patients who do not have these
      disorders but who are actively developing large numbers of new skin cancers may
      also benefit from this approach. All patients developing large numbers of skin
      cancers need rigorous UV protection and frequent dermatologic examinations.
      Although isotretinoin and acitretin share overlapping toxicities, there are
      differences that may affect drug choice. Because low doses may be effective,
      there are advantages to beginning treatment at a low dose, and subsequently,
      increasing dose if necessary, based on patient response. Laboratory monitoring
      including pregnancy testing should be performed before and during treatment. Long
      term toxicity, primarily involving the skeletal system, can be monitored with
      imaging studies.

PMID- 17014487
TI  - Perception and modification of plant flavonoid signals by rhizosphere
      microorganisms.
AB  - Flavonoids are a diverse class of polyphenolic compounds that are produced as a
      result of plant secondary metabolism. They are known to play a multifunctional
      role in rhizospheric plant-microbe and plant-plant communication. Most familiar
      is their function as a signal in initiation of the legume-rhizobia symbiosis,
      but, flavonoids may also be signals in the establishment of arbuscular
      mycorrhizal symbiosis and are known agents in plant defence and in allelopathic
      interactions. Flavonoid perception by, and impact on, their microbial targets
      (e.g. rhizobia, plant pathogens) is relatively well characterized. However,
      potential impacts on 'non-target' rhizosphere inhabitants ('non-target' is used
      to distinguish those microorganisms not conventionally known as targets) have not
      been thoroughly investigated. Thus, this review first summarizes the conventional
      roles of flavonoids as nod gene inducers, phytoalexins and allelochemicals before
      exploring questions concerning 'non-target' impacts. We hypothesize that
      flavonoids act to shape rhizosphere microbial community structure because they
      represent a potential source of carbon and toxicity and that they impact on
      rhizosphere function, for example, by accelerating the biodegradation of
      xenobiotics. We also examine the reverse question, 'how do rhizosphere microbial
      communities impact on flavonoid signals?' The presence of microorganisms
      undoubtedly influences the quality and quantity of flavonoids present in the
      rhizosphere, both through modification of root exudation patterns and microbial
      catabolism of exudates. Microbial alteration and attenuation of flavonoid signals
      may have ecological consequences for below-ground plant-microbe and plant-plant
      interaction. We have a lack of knowledge concerning the composition,
      concentration and bioavailability of flavonoids actually experienced by microbes
      in an intact rhizosphere, but this may be addressed through advances in
      microspectroscopic and biosensor techniques. Through the use of plant mutants
      defective in flavonoid biosynthesis, we may also start to address the question of
      the significance of flavonoids in shaping rhizosphere community structure and
      function.

PMID- 17014488
TI  - Biogeography of the marine actinomycete Salinispora.
AB  - Marine actinomycetes belonging to the genus Salinispora were cultured from marine
      sediments collected at six geographically distinct locations. Detailed
      phylogenetic analyses of both 16S rRNA and gyrB gene sequences reveal that this
      genus is comprised of three distinct but closely related clades corresponding to
      the species Salinispora tropica, Salinispora arenicola and a third species for
      which the name 'Salinispora pacifica' is proposed. Salinispora arenicola was
      cultured from all locations sampled and provides clear evidence for the
      cosmopolitan distribution of an individual bacterial species. The co-occurrence
      of S. arenicola with S. tropica and S. pacifica suggests that ecological
      differentiation as opposed to geographical isolation is driving speciation within
      the genus. All Salinispora strains cultured to date share greater than 99% 16S
      rRNA gene sequence identity and thus comprise what has been described as a
      microdiverse ribotype cluster. The description of this cluster as a new genus,
      containing multiple species, provides clear evidence that fine-scale 16S rDNA
      sequence analysis can be used to delineate among closely related species and that
      more conservative operational taxonomic unit values may significantly
      underestimate global species diversity.

PMID- 17014489
TI  - Does disturbance and restoration of alpine grassland soils affect the genetic
      structure and diversity of bacterial and N2-fixing populations?
AB  - Responses of bacterial communities to disturbance and restoration processes were
      investigated on alpine grassland soil. Bulk soil, rhizosphere soil and two soil
      separates, i.e. sand-size (2000-200 microm) and silt-size (50-2 microm) were
      sampled from undisturbed grassland soil to soil under restoration for 1 month, 1
      year, 4 years and 13 years after disturbance. Automated ribosomal intergenic
      spacer analysis (ARISA) and restriction fragment length polymorphism (RFLP) of
      nifH gene pools were used to assay genetic structure of the bacterial communities
      and N2-fixing guild. According to the distribution of ARISA band length in
      bacterial phyla, the dominance of ARISA bands below 400 bp showed that Gram
      positive bacteria would be predominant in the studied grassland soil when not
      disturbed. Disturbance affected the genetic structure of bacterial community and
      of N2-fixing guild in relation to their location within the selected habitats.
      Shifts in IGS and nifH profiles of bulk soil metagenome were larger than those
      observed from sand-size- and silt-size-fractions, accounting for 40-50% of the
      variance in the profiles. Restoration of the genetic structure of telluric
      bacteria community and N2-fixing populations was found to be influenced by the
      spatial heterogeneity of the soil and niche diversification. Particular bacterial
      genetic structure within distinct habitats were evidenced and must be defined as
      subdivisions of the meta-community of bulk soil. Scale of soil microbial
      diversity/stability relationships is discussed with special attention to
      disconnected bacterial habitat compared with whole soil with multiple niches.

PMID- 17014490
TI  - Off-axis symbiosis found: Characterization and biogeography of bacterial
      symbionts of Bathymodiolus mussels from Lost City hydrothermal vents.
AB  - Organisms at hydrothermal vents inhabit discontinuous chemical 'islands' along
      mid-ocean ridges, a scenario that may promote genetic divergence among
      populations. The 2003 discovery of mussels at the Lost City Hydrothermal Field
      provided a means of evaluating factors that govern the biogeography of symbiotic
      bacteria in the deep sea. The unusual chemical composition of vent fluids, the
      remote location, and paucity of characteristic vent macrofauna at the site,
      raised the question of whether microbial symbioses existed at the extraordinary
      Lost City. If so, how did symbiotic bacteria therein relate to those hosted by
      invertebrates at the closest known hydrothermal vents along the Mid-Atlantic
      Ridge (MAR)? To answer these questions, we performed microscopic and molecular
      analyses on the bacteria found within the gill tissue of Bathymodiolus mussels
      (Mytilidae, Bathymodiolinae) that were discovered at the Lost City. Here we show
      that Lost City mussels harbour chemoautotrophic and methanotrophic endosymbionts
      simultaneously. Furthermore, populations of the chemoautotrophic symbionts from
      the Lost City and two sites along the MAR are genetically distinct from each
      other, which suggests spatial isolation of bacteria in the deep sea. These
      findings provide new insights into the processes that drive diversification of
      bacteria and evolution of symbioses at hydrothermal vents.

PMID- 17014491
TI  - Characterization of diatom-cyanobacteria symbioses on the basis of nifH, hetR and
      16S rRNA sequences.
AB  - Richelia intracellularis is a symbiotic heterocystous cyanobacterium that is
      capable of forming associations with several genera of diatoms. nifH, 16S rRNA
      and hetR sequences were amplified and cloned from field populations of Richelia
      associated with Hemiaulus hauckii (N. Atlantic), with Rhizosolenia clevei (N.
      Pacific), and from a cultivated isolate of Calothrix associated with Chaetoceros
      from station ALOHA (N. Pacific). Sequence identity was highest (98.2%) among the
      16S rRNA sequences, and more divergent for the hetR (83.8%) and nifH (91.1%)
      sequences. The hetR and nifH DNA and amino acid sequences obtained from the
      symbionts associated with the three different diatom genera diverged into three
      separate lineages supported by high bootstrap values. The data indicate that
      symbionts in the different hosts are distinct species or strains. Furthermore,
      three previously unidentified heterocystous-like nifH sequence groups recently
      reported from station ALOHA in the subtropical Pacific, het-1, het-2 and het-3,
      were linked to Richelia associated with R. clevei, H. hauckii and the Calothrix
      symbiont of Chaetoceros sp. respectively.

PMID- 17014492
TI  - Transport of radiocaesium by arbuscular mycorrhizal fungi to Medicago truncatula
      under in vitro conditions.
AB  - The capacity of arbuscular mycorrhizal (AM) fungi to take up and translocate
      radiocaesium (Cs) to their host has been shown using the root-organ culture (ROC)
      system. However, the absence of photosynthetic tissues, lack of a normal root
      hormonal balance and incomplete source-sink relationships may bias the
      bidirectional transfer of elements at the symbiotic interface and complicate
      transport studies. Accordingly, we developed a novel culture system [i.e. the
      Arbuscular Mycorrhizal-Plant (AM-P) in vitro culture system], where AM fungi and
      an autotrophic host plant develop under strict in vitro conditions. With this
      system, we unambiguously demonstrated the capacity of AM fungi to transport Cs.
      The extraradical fungal hyphae took up 21.0% of the initial supply of 134Cs.
      Translocation to the plant represented 83.6% of the 134Cs taken up. Distribution
      of 134Cs in the host plant was 89.8% in the mycorrhizal roots and 10.2% in the
      shoot. These results confirm that AM fungi can take up, translocate and
      accumulate Cs. They further demonstrate unambiguously and for the first time that
      Cs can be transferred from AM fungi to host tissues. These results suggest a
      potential involvement of AM fungi in Cs biogeochemical cycle and in plant Cs
      accumulation.

PMID- 17014493
TI  - Novel lipids in Myxococcus xanthus and their role in chemotaxis.
AB  - Organisms that colonize solid surfaces, like Myxococcus xanthus, use novel
      signalling systems to organize multicellular behaviour. Phosphatidylethanolamine
      (PE) containing the fatty acid 16:1omega5 (Delta11) elicits a chemotactic
      response. The phenomenon was examined by observing the effects of PE species with
      varying fatty acid pairings. Wild-type M. xanthus contains 17 different PE
      species under vegetative conditions and 19 at the midpoint of development; 13 of
      the 17 have an unsaturated fatty acid at the sn-1 position, a novelty among
      Proteobacteria. Myxococcus xanthus has two glycerol-3-phosphate acyltransferase
      (PlsB) homologues which add the sn-1 fatty acid. Each produces PE with 16:1 at
      the sn-1 position and supports growth and fruiting body development. Deletion of
      plsB1 (MXAN3288) results in more dramatic changes in PE species distribution than
      deletion of plsB2 (MXAN1675). PlsB2 has a putative N-terminal eukaryotic fatty
      acid reductase domain and may support both ether lipid synthesis and PE
      synthesis. Disruption of a single sn-2 acyltransferase homologue (PlsC, of which
      M. xanthus contains five) results in minor changes in membrane PE. Derivatization
      of purified PE extracts with dimethyldisulfide was used to determine the position
      of the double bonds in unsaturated fatty acids. The results suggest that Delta5
      and Delta11 desaturases may create the double bonds after synthesis of the fatty
      acid. Phosphatidylethanolamine enriched for 16:1 at the sn-1 position stimulates
      chemotaxis more strongly than PE with 16:1 enriched at the sn-2 position. It
      appears that the deployment of a rare fatty acid (16:1omega5) at an unusual
      position (sn-1) has facilitated the evolution of a novel cell signal.

PMID- 17014494
TI  - Recovery of temperate Desulfovibrio vulgaris bacteriophage using a novel host
      strain.
AB  - A novel sulfate-reducing bacterium (strain DePue) closely related to
      Desulfovibrio vulgaris ssp. vulgaris strain Hildenborough was isolated from the
      sediment of a heavy-metal impacted lake using established techniques. Although
      few physiological differences between strains DePue and Hildenborough were
      observed, pulse-field gel electrophoresis (PFGE) revealed a significant genome
      reduction in strain DePue. Comparative whole-genome microarray and polymerase
      chain reaction analyses demonstrated that the absence of genes annotated in the
      Hildenborough genome as phage or phage-related contributed to the significant
      genome reduction in strain DePue. Two morphotypically distinct temperate
      bacteriophage from strain Hildenborough were recovered using strain DePue as a
      host for plaque isolation.

PMID- 17014495
TI  - Microbial community related to volatile organic compound (VOC) emission in
      household biowaste.
AB  - Malodorous emissions and potentially pathogenic microorganisms which develop
      during domestic organic waste collection are not only a nuisance but may also
      pose health risks. The aim of the present study was to determine whether the
      presence of specific microorganisms in biowastes is directly related to the
      composition of the emitted volatile organic compounds (VOCs). The succession of
      microbial communities during 16 days of storage in organic waste collection bins
      was studied by denaturing gradient gel electrophoresis (DGGE) of amplified 16S
      ribosomal DNA in parallel with a classical cultivation and isolation approach.
      Approximately 60 different bacterial species and 20 different fungal species were
      isolated. Additionally, some bacterial species were identified through sequencing
      of excised DGGE bands. Proton transfer reaction mass spectrometry (PTR-MS) was
      used to detect VOCs over the sampling periods, and co-inertia analyses of VOC
      concentrations with DGGE band intensities were conducted. Positive correlations,
      indicating production of the respective VOC or enhancement of microbial growth,
      and negative correlations, indicating the use of, or microbial inhibition by the
      respective compound, were found for the different VOCs. Measurement of the VOC
      emission pattern from a pure culture of Lactococcus lactis confirmed the positive
      correlations for the protonated masses 89 (tentatively identified as butyric
      acid), 63 (tentatively identified as dimethylsulfide), 69 (likely isoprene) and
      73 (likely butanone).

PMID- 17014496
TI  - Identification of forces shaping the commensal Escherichia coli genetic structure
      by comparing animal and human isolates.
AB  - To identify forces shaping the Escherichia coli intraspecies ecological
      structure, we have characterized in terms of phylogenetic group (A, B1, D and B2)
      belonging, presence/absence of extraintestinal virulence genes (pap, sfa, hly and
      aer) and intra-host phylotype diversity a collection of 1898 commensal isolates
      originating from 387 animals (birds and mammals) sampled in the 1980s and the
      2000s. These data have been compared with 760 human commensal isolates, sampled
      from 152 healthy subjects in the 2000s, and analysed with the same approach. The
      prevalence of the E. coli phylogenetic groups in birds, non-human mammals and
      humans is clearly different with a predominance of D/B1, A/B1 and A/B2 strains
      respectively. A major force shaping the ecological structure is the environment
      with a strong effect of domestication and the year of sampling followed by the
      climate. Host characteristics, as the diet and body mass, also influence the
      ecological structure. Human microbiota are characterized by a higher prevalence
      of virulence genes and a lower intra-host diversity than the non-human mammal
      ones. This work identifies for the first time a group of strains specific to the
      animals, the B1 phylogenetic group strains exhibiting the hly gene. In
      conclusion, a complex network of factors seems to shape the ecological structure
      of commensal E. coli, with anthropogenic factors playing a major role and
      perturbing natural niche equilibrium.

PMID- 17014497
TI  - Molecular analysis of ammonia-oxidizing bacteria community in intermittent
      aeration sequencing batch reactors used for animal wastewater treatment.
AB  - Bacterial communities and betaproteobacterial ammonia-oxidizing bacteria (AOB)
      communities were evaluated seasonally in an intermittent-aeration sequencing
      batch process (SBR, plant A) and in 12 other livestock wastewater treatment
      plants (WWTP): eight SBRs and four conventional activated-sludge systems.
      Microbial communities were analysed by reverse transcription polymerase chain
      reaction followed by denaturing-gradient gel electrophoresis (DGGE) and the
      construction of clone libraries for 16S rRNA and ammonia monooxygenase (amoA)
      genes. In plant A, the dominant bacteria were as-yet-uncultured bacteria of
      Bacteroidetes and Proteobacteria, and the DGGE profiles showed that the bacterial
      communities were stable during a given treatment cycle, but changed seasonally.
      In betaproteobacterial AOB communities, two AOB phylotypes (members of the
      Nitrosomonas ureae-oligotropha-marina cluster) were dominant during the seasons
      in plant A. Although the dominant AOB phylotypes differed among the 13 WWTPs,
      dominance by one or two AOB phylotypes was commonly observed in all plants.
      Sequencing of the DGGE bands indicated that amoA sequences belonging to the
      Nitrosomonas europaea-eutropha cluster were dominant in 11 plants, where the
      ammonia-nitrogen concentration was high in the raw wastewater, whereas those
      belonging to the Nitrosomonas ureae-oligotropha-marina cluster were dominant in
      two plants where the concentration was relatively low. Even though we detected
      many minor amoA sequences by means of five clone libraries for the A to D plants,
      no libraries comprised both amoA sequences belonging to the two clusters,
      indicating that the dominant AOBs were defined by cluster level in each plant.

PMID- 17014498
TI  - Biofilm formation and cellulose expression among diverse environmental
      Pseudomonas isolates.
AB  - The ability to form biofilms is seen as an increasingly important colonization
      strategy among both pathogenic and environmental bacteria. A survey of 185 plant
      associated, phytopathogenic, soil and river Pseudomonas isolates resulted in 76%
      producing biofilms at the air-liquid (A-L) interface after selection in static
      microcosms. Considerable variation in biofilm phenotype was observed, including
      waxy aggregations, viscous and floccular masses, and physically cohesive biofilms
      with continuously varying strengths over 1500-fold. Calcofluor epifluorescent
      microscopy identified cellulose as the matrix component in biofilms produced by
      Pseudomonas asplenii, Pseudomonas corrugata, Pseudomonas fluorescens, Pseudomonas
      marginalis, Pseudomonas putida, Pseudomonas savastanoi and Pseudomonas syringae
      isolates. Cellulose expression and biofilm formation could be induced by the
      constitutively active WspR19 mutant of the cyclic-di-GMP-associated, GGDEF domain
      containing response regulator involved in the P. fluorescens SBW25 wrinkly
      spreader phenotype and cellular aggregation in Pseudomonas aeruginosa PA01.
      WspR19 could also induce P. putida KT2440, which otherwise did not produce a
      biofilm or express cellulose, as well as Escherichia coli K12 and Salmonella
      typhimurium LT2, both of which express cellulose yet lack WspR homologues.
      Statistical analysis of biofilm parameters suggest that biofilm development is a
      more complex process than that simply described by the production of attachment
      and matrix components and bacterial growth. This complexity was also seen in
      multivariate analysis as a species-ecological habitat effect, underscoring the
      fact that in vitro biofilms are abstractions of those surface and volume
      colonization processes used by bacteria in their natural environments.

PMID- 17014499
TI  - The incidence of nirS and nirK and their genetic heterogeneity in cultivated
      denitrifiers.
AB  - Gene sequence analysis of nirS and nirK, both encoding nitrite reductases, was
      performed on cultivated denitrifiers to assess their incidence in different
      bacterial taxa and their taxonomical value. Almost half of the 227 investigated
      denitrifying strains did not render an nir amplicon with any of five previously
      described primers. NirK and nirS were found to be prevalent in
      Alphaproteobacteria and Betaproteobacteria, respectively, nirK was detected in
      the Firmicutes and Bacteroidetes and nirS and nirK with equal frequency in the
      Gammaproteobacteria. These observations deviated from the hitherto reported
      incidence of nir genes in bacterial taxa. NirS gene phylogeny was congruent with
      the 16S rRNA gene phylogeny on family or genus level, although some strains did
      group within clusters of other bacterial classes. Phylogenetic nirK gene sequence
      analysis was incongruent with the 16S rRNA gene phylogeny. NirK sequences were
      also found to be significantly more similar to nirK sequences from the same
      habitat than to nirK sequences retrieved from highly related taxa. This study
      supports the hypothesis that horizontal gene transfer events of denitrification
      genes have occurred and underlines that denitrification genes should not be
      linked with organism diversity of denitrifiers in cultivation-independent
      studies.

PMID- 17014500
TI  - Roseobacter and SAR11 dominate microbial glucose uptake in coastal North Sea
      waters.
AB  - Bacterial assemblages in coastal pelagic environments are exposed to pronounced
      temporal and spatial fluctuations in the availability of monomeric substrates.
      Little is known about the response of particular bacterial groups to such
      variability. We studied glucose incorporation at various concentrations (0.1-100
      nM) by bacteria related to Roseobacter, SAR11, Gammaproteobacteria and Cytophaga
      Flavobacteria in coastal North Sea waters in late winter and during a spring
      phytoplankton bloom dominated by Phaeocystis sp. (March and May 2004
      respectively). Both the fraction of glucose-assimilating bacterial cells and the
      rate of substrate incorporation per active cell were higher in May. The
      respective contributions of the studied groups to all glucose-assimilating
      Bacteria were related to substrate concentration. The majority of glucose
      incorporating bacterial cells at the lower concentrations were members of the
      Roseobacter and SAR11 clades. At both time-points the two groups formed
      approximately equal fractions of all glucose-incorporating bacteria. This was due
      to a small population of highly active Roseobacter cells and high abundances of
      SAR11 bacteria with low proportions of glucose-incorporating cells. By contrast,
      the proportion of active cells from the Cytophaga-Flavobacteria lineage
      substantially increased at higher levels of available substrate. The
      determination of concentration-dependent substrate incorporation patterns may
      help to better understand the different ecophysiological niches of
      bacterioplankton populations.

PMID- 17014501
TI  - Pressure affects transcription profiles of Methanocaldococcus jannaschii despite
      the absence of barophilic growth under gas-transfer limitation.
AB  - Barophilic growth of the hyperthermophilic methanarchaeon Methanocaldococcus
      jannaschii occurred when gas-substrate availability did not limit growth. In
      contrast, when growth was limited by gas transfer, no enhancement of growth was
      evident and a stress response was exhibited at both high and low pressure. A
      pressure-induced transcriptional response was evident, regardless of whether
      growth was enhanced by pressure. Potential high-pressure adaptation of a
      barophilic organism can thus occur at the transcriptional level, even though the
      cells are stressed by low substrate availability and do not exhibit accelerated
      growth.

PMID- 17014502
TI  - Vertical distribution of nitrifying populations in bacterial biofilms from a full
      scale nitrifying trickling filter.
AB  - Cryosectioned biofilm from three depths (0.5, 3.0 and 6.0 m) in a full-scale
      nitrifying trickling filter (NTF) were studied using fluorescence in situ
      hybridization (FISH). A large number of sections were used to determine how the
      biofilm thickness, structure and community composition varied with depth along
      the ammonium concentration gradient in the NTF, and how the ammonia-oxidizing
      bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were distributed vertically
      within the biofilm. Both the biofilm thickness and relative biomass content of
      the biofilm decreased with depth, along with structural differences such as void
      size and surface roughness. Four AOB populations were found, with two
      Nitrosomonas oligotropha populations dominating at all depths. A smaller
      population of Nitrosomonas europaea was present only at 0.5 m, while a population
      of Nitrosomonas communis increased with depth. The two N. oligotropha populations
      showed different vertical distribution patterns within the biofilm, indicating
      different ecophysiologies even though they belong to the same AOB lineage. All
      NOB were identified as Nitrospira sp., and were generally more associated with
      the biofilm base than the surface-associated dominating AOB population.
      Additionally, a small population of anaerobic ammonia-oxidizers was found at 6.0
      m, even though the biofilm was well aerated.

PMID- 17014503
TI  - Archaeal diversity in two thermophilic chalcopyrite bioleaching reactors.
AB  - This study used a culture-independent molecular approach to investigate the
      archaeal community composition of thermophilic bioleaching reactors. Two culture
      samples, MTC-A and MTC-B, grown with different concentrations of chalcopyrite
      (CuFeS2), a copper sulfidic ore, at a temperature of 78 degrees C and pH 1.6 were
      studied. Phylogenetic analysis of the 16S rRNA genes revealed that both cultures
      consisted of Archaea belonging to the Sulfolobales. The 16S rRNA gene clone
      library of MTC-A grown with 4% (w/v) chalcopyrite was dominated by a unique
      phylotype related to Sulfolobus shibatae (69% of total clones). The remaining
      clones were affiliated with Stygiolobus azoricus (11%), Metallosphaera sp. J1
      (8%), Acidianus infernus (2%), and a novel phylotype related to Sulfurisphaera
      ohwakuensis (10%). In contrast, the clones from MTC-B grown with 12% (w/v)
      chalcopyrite did not appear to contain Sulfolobus shibatae-like organisms.
      Instead the bioleaching consortium was dominated by clones related to
      Sulfurisphaera ohwakuensis (73.9% of total clones). The remaining microorganisms
      detected were similar to those found in MTC-A.

PMID- 17014506
TI  - The kidney disease wasting: inflammation, oxidative stress, and diet-gene
      interaction.
AB  - The 350,000 maintenance hemodialysis (MHD) patients in the United States have an
      unacceptably high mortality rate of >20%/year. Almost half of all deaths are
      assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as
      hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional
      cardiovascular risk factors, appear to be the strongest predictors of early death
      in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX
      markers as serum myeloperoxidase are associated with pro-inflammatory cytokines
      and poor survival in MHD patients. Identifying the conditions that modulate the
      KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional
      lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory
      index (HII) may engender or aggravate the KDW, whereas functionally intact or
      larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate
      the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good"
      phenomenon may be observed. Diet and gene and their complex interaction may lead
      to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII,
      resulting in the aggravation of the SOX and inflammatory processes, endothelial
      dysfunction, and subsequent atherosclerotic cardiovascular disease and death in
      MHD patients. Understanding the factors that modulate the KDW/SOX complex and
      their associations with genetic polymorphism, nutrition, and outcomes in MHD
      patients may lead to developing more effective strategies to improve outcomes in
      this and the 20 to 30 million Americans with chronic disease states such as
      individuals with chronic heart failure, advanced age, malignancies, AIDS, or
      cachexia.

PMID- 17014507
TI  - Review of dialysate calcium concentration in hemodialysis.
AB  - The dialysate calcium (Ca) concentration for hemodialysis (HD) patients can be
      adjusted to manage more optimally the body's Ca and phosphate balance, and thus
      improve bone metabolism as well as reduce accelerated arteriosclerosis and
      cardiovascular mortality. The appropriate dialysate Ca concentration allowing
      this balance should be prescribed to each individual patient depending on a
      multitude of variable factors relating to Ca load. A lower dialysate Ca
      concentration of 1.25 to 1.3 mmol/L will permit the use of vitamin D supplements
      and Ca-based phosphate binders in clinical practice, with much less risk of Ca
      loading and resultant hypercalcemia and calcification. Low Ca baths are useful in
      the setting of adynamic bone disease where an increase in bone turnover is
      required. However, low Ca levels in the dialysate may also predispose to cardiac
      arrhythmias and hemodynamically unstable dialysis sessions with intradialytic
      hypotension. Higher Ca dialysate is useful to sustain normal serum Ca levels
      where patients are not taking Ca-based binders or if Ca supplements are not able
      to normalize serum levels. Suppression of hyperparathyroidism is also effective
      with dialysate Ca of 1.75 mmol/L, but hypercalcemia, metastatic calcification,
      and oversuppression of parathyroid hormone are risks. Dialysate Ca of 1.5 mmol/L
      may be a compromise between bone protection and reduction in cardiovascular risk
      for conventional HD and is a common concentration used throughout the world. The
      increase in longer, more frequent dialysis such as short-daily and nocturnal HD,
      however, provides another challenge with regard to optimal dialysate Ca levels
      and higher levels of 1.75 mmol/L are probably indicated in this setting.
      Difficulties in determining the ideal dialysate Ca occur because of the complex
      pathophysiology of bone and mineral metabolism in HD patients and there needs to
      be a balance between dialysis prescription and other treatment modalities. To
      optimize management of the abnormal Ca balance, other aspects of this disorder
      need to be more fully clarified and, with evolving medications for phosphate
      control and treatment of secondary hyperparathyroidism, as well as the emergence
      of a multitude of different HD regimes, further studies are required to make
      definitive recommendations. At present, we need to maintain flexibility with HD
      treatments and so dialysate Ca needs to be individualized to meet the specific
      requirements of patients by optimizing management of renal bone disease and
      simultaneously reducing metastatic calcification and cardiovascular disease.

PMID- 17014508
TI  - Management of hyperphosphatemia.
AB  - Hyperphosphatemia is a well recognized risk factor for cardiovascular mortality
      in dialysis patients. Despite advanced technology and regular and efficient
      dialysis treatment the prevalence of hyperphosphatemia is still high. The goal of
      normalization of serum phosphorus (iP) levels can only be reached by optimization
      of dialysis prescription in combination with individualized dietary and medical
      strategies. Due to the unique characteristics of intradialytic iP kinetics,
      dialysis treatment time and frequency are the most effective factors governing
      intradialytic iP removal. Although the combination of diffusive and convective
      removal by hemodiafiltration allows a further increase in iP mass removal, a
      neutral phosphorus balance without dietary restrictions and the use of phosphate
      binders has only be achieved by daily nocturnal hemodialysis. Strict dietary
      phosphate restriction bears the risk of inadequate protein intake and the
      development of protein/calorie malnutrition. Although phosphate binders (PB) can
      effectively lower serum iP levels into the normal range, this is rarely achieved
      in clinical practice probably due to inadequate relation of PB dose to dietary
      phosphorus intake. Developing methods to enable patients to self-adjust phosphate
      binder dose to individual meal phosphate content, similar to adjusting insulin
      dose to carbohydrate intake, may lead to further improvements in phosphate
      management.

PMID- 17014509
TI  - Continuous online monitoring of ionic dialysance allows modification of delivered
      hemodialysis treatment time.
AB  - Considerable intrinsic intrapatient variability influences the actual delivery of
      Kt/V. The aim of this study is to examine the feasibility of using continuous
      online assessment of ionic dialysance measurements (Kt/V(ID)) to allow dialysis
      sessions to be altered on an individual basis. Ten well-established chronic
      hemodialysis (HD) patients without significant residual renal function were
      studied (mean age 65+/-4.3 [38-81] years, mean length of time on dialysis 66+/-18
      [14-189] months). These patients had all been receiving thrice-weekly 4-hr
      dialysis using Integra dialysis monitors. Dialysis monitors were equipped with
      Diascan modules permitting measurement of Kt/V(ID). Predicted treatment time
      required to achieve a Kt/V(ID) > or = 1.1 (equivalent to a urea-based method of
      1.2) was calculated from the delivered Kt/V(ID) at 60 and 120 min. Treatment time
      was reprogrammed at 2 hr (ensuring all planned ultrafiltration would be
      accommodated into the new modified session duration). Owing to practical issues,
      and to avoid excessively short dialysis times, these changes were censored at no
      more than+/-10% of the usual 240-min treatment time (210-265 min). Data were
      collected from a total of 50 dialysis sessions. Almost all sessions (47/50)
      required modification of the standard treatment time: 13/50 sessions were
      lengthened and 34/50 shortened (mean length of session 232.2+/-2.5 [210-265]
      min). A Kt/V(ID) of > or = 1.1 was achieved in 39/50 sessions. The difference in
      mean urea-based Kt/V poststudy (1.3+/-0.05 [1.1-1.6]) and mean achieved Kt/V(ID)
      (1.16+/-0.02 [0.7-1.37]) was significant (p = 0.002). The use of individualized
      variable dialysis treatment time using online ionic dialysance measurements of
      Kt/V(ID) appears both practicable and effective at ensuring consistently
      delivered adequate dialysis.

PMID- 17014510
TI  - Evaluation of cortical bone by peripheral quantitative computed tomography in
      continuous ambulatory peritoneal dialysis patients.
AB  - Several studies have suggested an increased prevalence of osteopenia in dialysis.
      Peripheral quantitative computed tomography (pQCT) is a new technique that allows
      the noninvasive evaluation of trabecular and cortical bone separately. The aim of
      the study was: (1) to evaluate cortical bone by pQCT in continuous ambulatory
      peritoneal dialysis (CAPD) patients and compare the data with that obtained in
      healthy controls; and (2) to correlate cortical bone parameters with bone mineral
      density (BMD) of the lumbar spine and femoral neck and total bone mineral content
      (TBMC). Cortical bone parameters were obtained in 22 CAPD patients and 27 healthy
      individuals at the distal radius using a Stratec XCT 960 pQCT machine. In the
      dialysis patients, we also determined BMD and TBMC by bone densitometry. Dialysis
      patients, compared with controls, showed a significant reduction in volumetric
      cortical BMD (VcBMD) (p = 0.04) and cortical thickness (cThk) (p < 0.0001) with a
      significant increase in radial total cross-sectional area (TA) (p = 0.006),
      endosteal circumference (p < 0.0001), and buckling ratio (p < 0.0001). In CAPD
      patients, total time on dialysis correlated negatively with radial total BMD (p <
      0.01) and VcBMD (p < 0.01). Age correlated positively with TA (p < 0.01),
      endosteal (p < 0.01), and periosteal circumferences (p < 0.01). Serum intact
      parathyroid hormone (PTH) levels correlated positively with endosteal (p = 0.04)
      and periosteal perimeter (p = 0.01). Total alkaline phosphatase correlated
      negatively with VcBMD (p < 0.01), and positively with endosteal perimeter (p =
      0.02). Total bone mineral content correlated significantly with radial cortical
      content (p < 0.001), cross-sectional cortical area (cA; p < 0.001), and cThk (p <
      0.01) but not with total radial BMD, VcBMD, or buckling ratio. No correlations
      were found between radial cortical parameters and BMD measured at the lumbar
      spine or femoral neck. We conclude that dialysis patients show cortical
      osteopenia with marked cortical thinning partially mediated by PTH action on
      bone. Total bone mineral content correlated with various radial cortical
      parameters (content, area, and thickness) but not with others. No correlations
      were found between cortical bone parameters measured at the peripheral skeleton
      with areal bone density measured at the axial skeleton. These findings suggest
      that pQCT may be a new tool in the assessment of bone fragility in dialysis
      patients.

PMID- 17014511
TI  - Doppler echocardiograph evaluation of pulmonary hypertension in patients
      undergoing hemodialysis.
AB  - Pulmonary hypertension (PH) has been reported in hemodialysis (HD) patients, but
      data regarding its incidence and mechanisms are scarce. The aims of this study
      was to evaluate the prevalence of unexplained PH in long-term HD patients, and to
      examine some possible etiologic factors for its occurrence. The prevalence of PH
      was estimated by Doppler echocardiography in a cohort of 86 stable patients on HD
      via arteriovenous access for more than 12 months. All the patients underwent full
      clinical evaluation, chest radiography, and a standard 12-lead echocardiograph.
      Laboratory investigation included a mean of 12 months (serum calcium, phosphorus,
      parathormone (PTH), alkaline phosphatase, lipids, and hemoglobin). Pulmonary
      hypertension was defined as pulmonary artery systolic pressure >35 mmHg as
      determined by Doppler echocardiography using the modified Bernoulli equation.
      Pulmonary hypertension was detected in 23 patients (26.74%). Of those with PH,
      left ventricular hypertrophy was seen in 13 patients (56.52%), and valvular
      calcifications in 6 patients (26.08%). There were no significant differences
      between both groups with regard to age, sex, duration of dialysis, shunt
      location, and all the biological parameters of the study. The presence of PH was
      not related to the level of PTH, or the severity of other metabolic
      abnormalities. This study demonstrates a high prevalence of PH among patients
      with ESRD receiving long-term HD via surgical arteriovenous access. The role of
      the vascular access, anemia, or secondary hyperparathyroidism as the etiology of
      PH in HD patients did not hold in this study.

PMID- 17014512
TI  - Tuberculosis in end-stage renal disease patients on hemodialysis.
AB  - Recent studies have shown that there is an increase in the incidence of
      mycobacterium tuberculosis (MBT). This is more prevalent among immune compromised
      patients (those on dialysis) and recipients of organ transplants. Furthermore,
      extra-pulmonary presentation appears to be more common and difficult to diagnose.
      We aimed in this study to assess and evaluate the presentation of MBT in a
      retrospective study conducted among 256 hemodialysis (HD) patients where 18 of
      them were diagnosed and managed for tuberculosis over a 10-year period between
      1990 and 2000. The mean age of the patients was 38 years (21-75 years). The mean
      interval between the onset of HD and the time of diagnosis was about 24 months (1
      120 months). The diagnosis of tuberculosis was made either by isolation of acid
      fast bacilli (AFB), the typical caseating granuloma on biopsy, or by recovery of
      tubercle bacilli from the culture of the biopsy material. Extra-pulmonary
      tuberculosis was more common (77.8%) than pulmonary tuberculosis (22.2%). The
      various extra-pulmonary tuberculosis sites noted were cervical lymphadenitis
      (16.7%), gastrointestinal (16.7%), genitourinary (11.1%), peritonitis (11.1%),
      pleural effusion (5.6%), pericardial effusion (5.6%), miliary tuberculosis
      (5.6%), and pyrexia of unknown origin (5.6%). None of the patients with extra
      pulmonary tuberculosis had evidence of pulmonary tuberculosis. The atypical
      presentation with insidious onset was quite common. Anergy to tuberculin skin
      test was noticed in 56% of cases. All of our patients received modified
      antituberculosis treatment for 1 year with adequate response, and without undue
      side effects. We conclude that a high index of suspicion is required especially
      in the diagnosis of extra-pulmonary tuberculosis, and when there is a high
      percentage of anergy to tuberculin skin test. Tissue biopsy both for
      characteristic histology and demonstration of MTB, either by staining or culture,
      remains the main criteria for the diagnosis of extra-pulmonary tuberculosis.

PMID- 17014513
TI  - Surveillance cultures of tunneled cuffed catheter exit sites in chronic
      hemodialysis patients are of no benefit.
AB  - Catheter-related infections are a major cause of morbidity and mortality in
      hemodialysis (HD) patients. This study evaluated the utility of surveillance swab
      cultures (Ssc) of tunneled cuffed catheter (TCC) exit sites as a prediction and
      prevention strategy for infection. A 6-month prospective-controlled trial with 94
      chronic HD patients with a TCC who received monthly Ssc and were stratified by
      dialysis day into topical therapy based on Ssc results (Group A) or no therapy
      (Group B). Outcomes were exit site infection (ESI) and catheter-associated
      bacteremia (CAB). The overall monthly prevalence of positive Ssc was 14.9%. There
      was no difference in the number of positive Ssc (17.7% vs. 11.6%, p > 0.05) or
      ESI (19.6% vs.16.3%, p > 0.05) between Groups A and B, respectively. Catheter
      associated bacteremia was higher in Group A (17.7% vs. 4.7%, p = 0.05). There
      were significantly more ESI in the patients treated for a positive Ssc. In Group
      A, the incidence of ESI was significantly higher in those treated for a positive
      vs. negative Ssc (55% vs. 12%, p = 0.009) and CAB rates trended higher with
      positive Ssc (22.2% vs. 16.7%, p > 0.05). The strategy of treating positive
      surveillance cultures is not beneficial. Positive Ssc do not predict the
      occurrence of catheter-related infection, and treatment of these cultures may
      lead to increased infection rates.

PMID- 17014514
TI  - Comparison of survival between short-daily hemodialysis and conventional
      hemodialysis using the standardized mortality ratio.
AB  - More frequent hemodialysis (5 or more times weekly, both short during the day and
      long overnight) has been shown to improve patient well-being, reduce symptoms
      during and between treatments, and have beneficial effects on clinical outcomes.
      Because of the relatively small patient sample sizes, there are little or no data
      on mortality from any single study at this time. This study compares survival in
      117 U.S. patients treated by short-daily hemodialysis in 2003 and 2004, with
      patients reported in the 2003 data from the United States Renal Data System
      (USRDS). Expected mortality was calculated from the USRDS and compared with
      observed actual mortality. The standardized mortality ratio (SMR) was used to
      adjust for differences in patient age, sex, race, and cause of renal failure. The
      SMR for the short-daily hemodialysis patients was 0.39, statistically
      significantly better (p < 0.005) than data from the overall U.S. population of
      hemodialysis patients and indicating that daily hemodialysis patients had a 61%
      better survival. Patients treated by short-daily hemodialysis have a better
      survival rate than comparable populations treated by conventional hemodialysis.

PMID- 17014515
TI  - Prevalence rate of Cryptosporidium infection in hemodialysis patients in Iran.
AB  - Cryptosporidium is one of the most common causes of diarrhea in the world, which
      can be severe and prolonged in immunocompromised patients. We compared the
      prevalence rate of Cryptosporidium infection in hemodialysis patients and 2
      control groups (i.e., their healthy family members and normal population). Stool
      specimens of 104 adult outpatient chronic hemodialysis patients, their 91 healthy
      family members, and 140 healthy individuals were examined for the presence of
      Cryptosporidium oocysts by using a modified acid-fast staining method. Twelve
      (11.5%) dialysis patients were infected with Cryptosporidium. This was
      significantly higher than 4 (4.4%), and 5 (3.6%) cases in the 2 control groups,
      respectively (p < 0.05). There was no significant difference between the 2
      control groups. The prevalence rate of Cryptosporidium infection did not
      correlate with patients' sex, age, duration of dialysis, history of kidney
      transplantation, or history of taking immunosuppressive drugs. However, it was
      significantly higher in diabetics vs. nondiabetics (19.4% vs. 8.3%, respectively,
      p < 0.05). Our results indicate that the prevalence rate of Cryptosporidium
      infection is considerably higher in dialysis patients than in the general
      population. Moreover, dialyzed diabetic patients had the highest rate of
      infection. As hemodialysis patients are candidates for renal transplantation,
      general preventive measures against acquiring Cryptosporidium infection must be
      considered.

PMID- 17014516
TI  - Flow distribution analysis by helical scanning in polysulfone hemodialyzers:
      effects of fiber structure and design on flow patterns and solute clearances.
AB  - The efficiency of a hemodialyzer is largely dependent on its ability to
      facilitate diffusion, as this is the main mechanism by which small solutes are
      removed. The diffusion process can be impaired if there is a mismatch between
      blood and dialysate flow distribution in the dialyzer. The objective of the paper
      was to study the impact of different fiber bundle configurations on blood and
      dialysate flow distribution and urea clearances. The Optiflux 200 NR hemodialyzer
      was studied and the standard F 80 A hemodialyzer was used as a control for the
      study. Six dialyzers of each type were studied in vitro in the radiology
      department utilizing a new generation of helical computed tomography (CT) scan
      following contrast medium injection into the blood and dialysate compartment.
      Dynamic sequential imaging of longitudinal sections of the dialyzer was
      undertaken to detect flow distribution, average and peak velocities, and
      calculate wall shear rates. Six patients were dialyzed with 2 different dialyzers
      in random consecutive sequence. In these patients, 2 consecutive dialyses were
      carried out with identical operational parameters (Qb = 300 mL/min, Qd = 500
      mL/min). In each session, blood and dialysate side urea clearances were measured
      at 30 and 150 min of treatment. Macroscopic and densitometrical analysis revealed
      that flow distribution was most homogeneous in the dialyzer with a new bundle
      configuration. Significantly increased urea clearances (p < 0.001) were seen with
      the Optiflux dialyzer compared with the standard dialyzer. In conclusion, more
      homogeneous dialysate blood and dialysate flow distribution and improved small
      solute clearances can be achieved by modifying the configuration of the filter
      bundle. These effects are achieved probably as a result of reduced blood to
      dialysate mismatch with reduction of flow channeling. The used radiological
      technique allows detailed flow distribution analysis and has the potential for
      testing future modifications to dialyzer design.

PMID- 17014517
TI  - Stability of nutritional parameters during a 5-year follow-up in patients treated
      with sequential long-hour hemodialysis.
AB  - Progressive nutritional impairment has been recently reported during conventional
      hemodialysis (HD) treatment. We studied the nutritional parameters during a 5
      year follow-up in HD patients. Thirty-three patients (15F/18M; 65 years old at
      the study start) filled out a 3-day food questionnaire once a year between 1995
      and 1999 (study group). Twenty patients, who did not fill out the food records
      during this period served as a control group (control group). The food record was
      run by the renal dietician using a dedicated software, providing daily energy and
      protein intakes (DEI and DPI). Serum albumin, normalized protein equivalent of
      nitrogen appearance (nPNA), and postdialysis body weight (BW) at the time of food
      record were collected in the study group and from the patient chart in the
      control group. The energy intake in the study group and the protein intake in
      both groups were close to the recommended intakes in ESRD patients. Protein
      intake assessed from food questionnaire or from urea kinetics were not
      statistically different. Using ANOVA for repeated measures, no difference along
      the 5 years was found for daily energy intake, daily protein intake, nPNA, and BW
      in the study group. The BW and nPNA remained stable in the control group. Hence,
      this study does not confirm the progressive nutritional impairment reported in
      the HEMO study, whereas the patients' age and vintage are largely higher in the
      present study. The role of a large dialysis dose in maintaining nutritional
      status in HD patients is discussed.

PMID- 17014518
TI  - Daily dialyses decrease plasma levels of brain natriuretic peptide (BNP), a
      biomarker of left ventricular dysfunction.
AB  - Brain natriuretic peptide or B-type natriuretic peptide (BNP) is a sensitive
      marker of heart disease. Plasma levels of BNP increase in left ventricular
      failure and determination of plasma BNP has become a useful tool in the diagnosis
      of heart failure. Hemodialysis (HD) patients may have elevated plasma levels of
      BNP, particularly predialysis, that correlate with echocardiographic signs of
      left ventricular dysfunction. High BNP levels are also a strong predictor of
      mortality in both nonrenal and HD patients. We studied plasma BNP levels in
      patients who changed from conventional thrice-weekly dialysis to daily dialysis 6
      times a week while maintaining a total weekly time on dialysis of 12 hr. Twelve
      HD patients, mean age 55 years, had 4 hr of conventional thrice-weekly treatment
      for 4 weeks. Predialysis and postdialysis blood samples were obtained at the last
      dialysis. Patients were then dialyzed for 2 hr, 6 times weekly, for 4 weeks
      (daily dialysis). Again, predialysis and postdialysis blood samples were
      collected at the last HD. Brain natriuretic peptide plasma concentrations were
      determined by immunoradiometric assay. Predialysis BNP levels decreased from
      194+/-51 ng/L (68+/-19 pmol/L; mean+SE) during thrice-weekly HD to 113+/-45 ng/L
      (41+/-18 pmol/L; p = 0.001) after 4 weeks on daily dialysis. With thrice-weekly
      HD, predialysis BNP levels were higher than postdialysis levels: 120+/-26 ng/L
      (39+/-8 pmol/L; p = 0.059). With daily dialysis, predialysis BNP levels did not
      differ significantly from postdialysis levels. Elevated predialysis plasma levels
      of BNP, considered sensitive and early markers of left ventricular dysfunction,
      decreased when patients were changed from conventional thrice-weekly HD to daily
      dialysis maintaining total hours of dialysis per week constant. Given the
      accumulated evidence that BNP is a biomarker of left ventricular dysfunction and
      can be used for risk stratification and guidance in pharmacotherapy of heart
      failure, daily dialysis appears to lead to less cardiac distress.

PMID- 17014519
TI  - Prognostic implications of clinical practice guidelines among hemodialysis
      patients.
AB  - Although the National Kidney Foundation (NKF) has published clinical practice
      guidelines for the management of risk factors for cardiovascular disease, these
      guidelines have not been tested rigorously for their effectiveness. We conducted
      an observational study among patients with end-stage kidney disease to examine
      the prognostic impact of threshold levels recommended by the NKF for blood
      pressure, hemoglobin, calcium-phosphate product, parathyroid hormone, low-density
      lipoprotein, and glycosylated hemoglobin. The study population (N = 197) was
      assembled from a previously completed randomized trial examining arteriovenous
      graft thrombosis. Cox proportional hazard analysis was used to calculate hazard
      ratios for the association of levels outside guideline recommended targets and
      death, adjusting for age, comorbidity, race, and albumin. The proportion of
      patients outside guideline targets ranged from 33% to 81%, and the impact of
      levels outside guideline targets on mortality varied substantially. Elevated
      calcium-phosphate product and glycosylated hemoglobin had harmful effects, with
      adjusted hazard ratios of 1.58 (95% CI 1.00-2.50; p = 0.050) and 2.21 (95% CI
      0.99-4.97; p = 0.054), respectively. Nontarget levels for blood pressure,
      hemoglobin, and parathyroid hormone had little effect, with adjusted hazard
      ratios of 1.15 (95% CI 0.74-1.78; p = 0.542), 1.04 (95% CI 0.65-1.68; p = 0.866),
      and 0.90 (95% CI 0.50-1.61; p = 0.722), respectively. Elevated low-density
      lipoprotein had a paradoxically beneficial effect, with an adjusted hazard ratio
      of 0.48 (95% CI 0.23-1.00; p = 0.049). These results suggest that the prognostic
      impact of current threshold levels recommended by select NKF guidelines on
      mortality is variable. Accordingly, the development and implementation of
      clinical practice guidelines should be accompanied by corresponding efforts to
      confirm their impact on patient outcomes. Such efforts are essential for the
      improvement of guidelines and to inform health policy optimally.

PMID- 17014521
TI  - The potential association between smoking and endodontic disease.
AB  - The aim of this review was to analyse the literature to assess the possibility of
      an association between smoking and endodontic disease and the prognosis of
      endodontically treated teeth. The review of the prognosis of endodontically
      treated teeth involved taking account of any potential associations with smoking
      and endodontic disease and marginal periodontitis, and smoking and prosthodontic
      outcomes. In addition, the role of smoking in implant failure and surgical wound
      healing was analysed with a view to drawing parallels regarding the possible
      implications of smoking on the outcome of surgical endodontics. A MEDLINE and
      Cochrane library search including smoking and various endodontic keyword searches
      identified three papers which discussed the variables, and did not just mention
      them separately in the text. The literature demonstrates a paucity of evidence
      relating smoking with endodontic disease and prognosis, but nevertheless presents
      evidence of a possible influence on the prognosis of endodontically treated teeth
      in smokers and a likely increase in surgical complications. The possible merits
      of a smoking cessation protocol prior to surgical endodontics are also discussed.

PMID- 17014522
TI  - Histological evaluation of the osteoinduction capability of human dentine.
AB  - Aim To assess whether human dentine has the potential to promote the development
      of calcified tissues when implanted in the muscle tissue of mice. Methodology
      Root canals in extracted human teeth were instrumented to produce dentine
      fragments. The dentine fragments produced were divided into two. In group 1,
      fragments were demineralized and sterilized. In group 2, the fragments were not
      submitted to any additional treatment. The dentine fragments were then implanted
      in the muscle of mice. In group 3, the muscles were implanted with rehydrated
      lyophilized human bone powder. Animals were killed following test periods of 7,
      15, 30, 60, 120 and 180 days, the fragments were removed together with adjacent
      muscle and examined under light microscopy to assess calcification. Results Areas
      of calcification were observed in groups 1 and 3 after a period of 180 days. In
      group 2, the surrounding tissues displayed only chronic inflammatory
      infiltration. Conclusions On the basis of the experimental model adopted in this
      study, fibroblast-rich connective tissue formed in groups 1 and 3, which could
      reflect an osteoinductive process. Further studies are suggested to identify
      which dentinal factors are capable of inducing the formation of a calcified
      matrix.

PMID- 17014523
TI  - The effect of temperature on viscosity of root canal sealers.
AB  - AIM: To test the hypothesis that there was no significant (alpha = 0.05) change
      in viscosity of commercially available root canal sealers with increase in
      temperature using a high-performance Advanced Rheometric Expansion System (ARES)
      rheometer. METHODOLOGY: Materials tested were Apexit, Tubliseal EWT, Grossman's,
      AH Plus and Ketac-endo. Cone-and-plate geometry was used (25-mm diameter, 0.1
      radian and gap 0.051 mm). Measurements were carried out for steady-state
      viscosity at 25 and 37 degrees C in the shear rate range of 0.001-50 s(-1) at
      standardized relative humidity and within 30 min from the start of mixing. Five
      samples were taken for each sealer at each temperature. RESULTS: At 25 degrees C
      all sealers demonstrated shear thinning. At 37 degrees C Grossman's (powder :
      liquid ratio 2 : 1 and 3 : 1) and Ketac-endo had a rapid rise in viscosity and
      early set whereas the other sealers were shear thinning. On increasing
      temperature from 25 degrees C to 37 degrees C, Apexit, Tubliseal and AH Plus had
      reduced viscosity whereas Grossman's 2 : 1, Grossman's 3 : 1 and Ketac-endo had
      increased viscosity, which varied with the shear rate. The change in viscosity
      with change in temperature was significant (P < 0.05) for all sealers except AH
      Plus. CONCLUSIONS: There was a variation in the effect of increasing temperature
      on each sealer depending on the shear rate. With the exception of AH Plus, a
      significant (P < 0.05) change in viscosity was found, and the null hypothesis was
      rejected.

PMID- 17014524
TI  - Radiographic technical quality of root fillings performed by dental students in
      Turkey.
AB  - AIM: To evaluate the radiographic technical quality of root fillings performed by
      undergraduate students at a dentistry faculty in Turkey. METHODOLOGY: A random
      sample of 2000 records of patients who received dental treatment at the Faculty
      of Dentistry, University of Gazi between 2000 and 2003 was investigated. The
      final sample consisted of 1,893 root-filled teeth with 3,692 root canals in 1,654
      dental patients. For each root-filled tooth, at least three periapical
      radiographs were examined: preoperative, working length determination and
      postoperative. The length, density and taper of root fillings were recorded. The
      length of root fillings was recorded as adequate, short or overfilled. Density of
      root fillings was recorded as adequate or inadequate. Taper of root fillings was
      recorded as adequate or inadequate. Results were evaluated statistically using
      one-way analysis of variance (anova) and chi-square analysis. RESULTS: Sixty-nine
      per cent, 53.2% and 68.3% of root fillings had adequate length, density and
      taper, respectively; only 33% of teeth fulfilled these three criteria at the same
      time. The relationship between the length, density and taper of the root filling
      and the presence of canal curvature was statistically significant (P < 0.001).
      There was no significant difference between maxillary and mandibular teeth
      according to the adequacy of the root fillings. The highest percentage of
      adequate root fillings was found in maxillary canines (51.5%). CONCLUSIONS: The
      percentage of adequate root fillings performed by undergraduate students was only
      33%.

PMID- 17014525
TI  - Root canal morphology of mandibular incisors in a Jordanian population.
AB  - AIM: To investigate the root canal morphology of mandibular incisors in a
      Jordanian population using a canal staining and tooth-clearing technique.
      METHODOLOGY: Four hundred and fifty extracted mandibular incisors were collected
      from dental clinics within north Jordan. Following pulp tissue removal and
      staining of the canal systems, the teeth were decalcified with 5% nitric acid,
      dehydrated with ascending concentrations of alcohol and rendered clear by
      immersion in methyl salicylate. Cleared teeth were examined by eye and the
      following features were evaluated: (i) number and type of root canals; (ii)
      presence and location of lateral canals and intercanal communications; (iii)
      location of apical foramina; and (iv) frequency of apical deltas. RESULTS: The
      majority of mandibular incisors had a single canal (73.8% of teeth possessed a
      Type I canal system). Although 26.2% of the roots possessed two canals, only 8.7%
      had two separate apical foramina. CONCLUSIONS: The prevalence of two canals in
      this group of mandibular incisors was 26.2% and is within the range of previous
      studies performed on populations of different racial origin.

PMID- 17014526
TI  - In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against
      selected single-species biofilms.
AB  - AIM: To investigate the antimicrobial activity of 2.5% and 5.25% sodium
      hypochlorite and 2.0% chlorhexidine gel and liquid as endodontic-irrigating
      substances against selected single-species biofilms. METHODS: Single-species
      biofilms of Enterococcus faecalis, Staphylococcus aureus, Candida albicans,
      Prevotella intermedia, Porphyromonas gingivalis, Porphyromonas endodontalis and
      Fusobacterium nucleatum were generated on a cellulose nitrate membrane placed on
      agar medium. The biofilms were then immersed in the endodontic-irrigating
      substances for 30 s and also for 5, 10, 15, 30 and 60 min, with and without
      mechanical agitation. Sterile saline was used as control. After each time period,
      the membrane filters were then transferred to tubes containing 2 mL of fresh
      broth medium plus neutralizers (in order to prevent the residual action of the
      tested substances). The micro-organisms were suspended using a vortex, and the
      inoculum was serially diluted 10-fold. Aliquots of the dilutions were plated on
      5% sheep blood agar medium, and incubated under adequate gaseous conditions.
      Colony-forming units were calculated. The samples were compared using the
      Friedman and Tukey test, when necessary, at a significance level of P < 0.05.
      RESULTS: Mechanical agitation promoted the effectiveness of the antimicrobial
      agents, resulting in less time to eliminate the same micro-organisms, except for
      S. aureus with 2.5% NaOCl. Antimicrobial agents in liquid presentation,
      especially 5.25% NaOCl and 2% chlorhexidine, killed the tested micro-organisms
      more rapidly. Saline did not inhibit the growth of any of the tested micro
      organisms, with or without agitation, being statistically different (P < 0.05)
      from NaOCl and chlorhexidine. P. intermedia, P. gingivalis, P. endodontalis and
      F. nucleatum were eliminated in 30 s by all antimicrobial agents, with our
      without agitation, in contrast with the facultative and aerobe strains.
      CONCLUSIONS: Mechanical agitation improved the antimicrobial properties of the
      chemical substances tested using a biofilm model, favouring the agents in liquid
      presentation, especially 5.25% NaOCl and 2% chlorhexidine.

PMID- 17014527
TI  - Survival of root filled cracked teeth in a tertiary institution.
AB  - AIM: To assess the survival rate of root filled cracked teeth over a 2-year
      period in a tertiary institute. METHODOLOGY: Forty-nine patients who had root
      canal treatment completed on their cracked teeth at the National Dental Centre
      (Singapore) were recalled for a 2-year review. Collected review data included
      presence of periodontal pocketing, sinus tract and swelling associated with the
      teeth. The date of extraction was noted if a tooth was missing at review. Pre
      treatment data collected were number, extent and location of crack, presence of
      periodontal pocketing, patients' age and gender, location of cracked teeth, type
      of teeth and presence of terminal cracked tooth. RESULTS: Fifty teeth in 49
      patients were included. The Kaplan-Meier estimate of 2-year survival rate was
      85.5% (95% confidence interval: 75.5-95.5). Cracked teeth which were the terminal
      teeth in the dental arch (RR = 4.9, 95% CI: 1.2-2.0, P = 0.04), teeth with pre
      root filling periodontal pocketing (RR = 4.9, 95% CI: 1.2-2.0, P = 0.04) and
      teeth with multiple cracks (RR = infinity, 95% CI: 1.9-infinity, P = 0.01) were
      more likely to be extracted. CONCLUSIONS: Within the limitations of this study,
      multiple cracks, terminal teeth and pre-root filling pocketing were significant
      prognostic factors for the survival of root filled cracked teeth.

PMID- 17014528
TI  - An ex vivo study of the effects of retained coronal dentine on the strength of
      teeth restored with composite core and different post and core systems.
AB  - AIM: To investigate the fracture resistance and fracture patterns of teeth
      restored with composite cores supported by different pre-fabricated post systems
      and different heights of remaining coronal dentine. METHODOLOGY: Four groups of
      30 single rooted teeth were used. Each group was divided into three subgroups of
      10 teeth each and restored with carbon fibre, glass fibre, or Radix titanium
      posts luted with dual cure resin cement. The control group A had no retained
      coronal dentine. Groups B, C and D had 2, 3 and 4 mm of retained buccal and
      lingual coronal dentine, respectively. Teeth were tested to failure using an
      Instron Universal Testing Machine. Subsequently, the fracture mode of specimens
      was recorded. RESULTS: Teeth with retained dentine were more resistant to
      fracture (P = 0.001). Tooth fracture resistance was not significantly different
      between groups B, C and D. Within group A, titanium posts were associated with
      higher fracture resistance than fibre posts. Within the other groups, tooth
      fracture resistance was not related to post material. Within groups C and D,
      fracture resistance of teeth restored with carbon fibre posts was significantly
      higher than those restored with glass fibre posts. The dominant fracture mode in
      group A was core and vertical oblique root fracture whilst a combination of core,
      coronal dentine and root fracture occurred in the other groups. CONCLUSIONS:
      Fracture resistance of teeth increased with the presence of retained coronal
      dentine. The use of glass and carbon fibre posts did not improve the fracture
      resistance or the fracture pattern of teeth when compared with metal titanium
      posts regardless of the presence of retained coronal dentine. The dominant
      fracture pattern of teeth was not related to the amount of retained dentine if it
      was >2 mm high.

PMID- 17014529
TI  - Effect of bonded restorations on the fracture resistance of root filled teeth.
AB  - AIM: To evaluate the fracture resistance of root filled maxillary premolars
      restored with different techniques. METHODOLOGY: One hundred and twenty single
      rooted maxillary premolar teeth were divided randomly into six groups of 20 teeth
      and subjected to the following procedures: group 1: intact teeth. Group 2:
      endodontic access cavities prepared. Group 3: MOD cavities were prepared, root
      canals were filled and no restoration was placed. Group 4: teeth were prepared as
      group 3 and restored conventionally with amalgam. Group 5: teeth were prepared as
      group 3 and restored with amalgam using a bonding material. Group 6: teeth were
      prepared as group 3 and restored with composite resin using the same bonding
      material. Teeth were embedded in acrylic resin and the loads for fracture
      strength were applied vertically with a constant speed of 1 mm min(-1). Data were
      evaluated statistically with anova and Tukey's tests. RESULTS: The mean force of
      fracture values were 1191.41, 599.86, 233.03, 494.72, 962.81 and 856.48 N for
      groups 1, 2, 3, 4, 5 and 6, respectively. The fracture resistance of group 5 was
      similar to group 1 (P > 0.05). The mean force at fracture of group 5 and group 6
      was not significantly different. The fracture resistance of groups 5 and 6 was
      significantly higher than group 4 (P < 0.001). CONCLUSIONS: The group, restored
      with conventional amalgam, had the weakest resistance to fracture when compared
      with the bonded restorations. No statistically significant differences were found
      between the bonded amalgam and composite resin groups.

PMID- 17014530
TI  - Proposal for a standardized protocol for the systematic orofacial examination of
      patients with Hereditary Sensory Radicular Neuropathy.
AB  - AIM: To apply a standardized protocol for the orofacial evaluation of two adult
      siblings (one male and one female) with Hereditary Sensory Radicular Neuropathy
      (HSRN) that presented with dental problems. SUMMARY: The systematic evaluation
      consisted of (a) clinical questionnaire; (b) radiographs [orthopantomography and
      computarized tomography (CT)]; (c) orofacial psychophysical tests (pain, thermal,
      mechanical and electrical sensation); and (d) histology of gingiva and pulp
      (optical and transmission electronic microscopy). The female patient had complete
      insensitivity to orofacial pain and partial facial heat sensitivity, and received
      dental treatment without anaesthesia or pain. She had a severe and painless jaw
      infection due to pulp necrosis in tooth 37. The male patient had partial
      insensitivity to orofacial pain and required anaesthesia for dental treatment.
      Histological examination of gingivae and pulpal tissue revealed an altered
      proportion of unmyelinated and myelinated sensory nerve fibres. KEY LEARNING
      POINTS: * Patients with HSRN may present with significant, silent dental disease.
      * A standard protocol is helpful when evaluating such patients. * If the
      opportunity arises, evaluation of pulp tissue may reveal an altered proportion of
      myelinated and unmyelinated nerve fibres. This may avoid the more estabilished
      sural nerve biopsy.

PMID- 17014531
TI  - Peripheral INSL3 concentrations decline with age in a large population of
      Australian men.
AB  - The novel peptide hormone insulin-like peptide 3 (INSL3) is a major secretory
      product of the Leydig cells of the testis, and in adult men is secreted into the
      blood, giving rise to circulating concentrations ranging from 0.5 to 2.5 ng/mL.
      We studied a large randomly recruited cohort of 1183 men from South Australia,
      comparing serum INSL3 concentrations with age, and a variety of endocrine,
      cognitive and morphological parameters. While INSL3 concentration declines
      significantly (p < 0.001) and continuously with age from 1.29 +/- 0.47 ng/mL in
      young men (age 35-44 years) to 0.79 +/- 0.39 ng/mL in the age group 75-80 years,
      there is no correlation with testosterone or components of the hypothalamo
      pituitary-gonadal (HPG) axis, independent of age, nor with any other parameter
      measured, including thyroid or prostate status and obesity. For men exhibiting
      normal follicle stimulating hormone (FSH) and high luteinizing hormone (LH)
      levels, there was a significant inverse correlation with plasma oestradiol.
      Unilaterally orchidectomized men had INSL3 values intermediate between intact men
      and anorchid subjects, and showed inverse correlations (p < 0.001) between INSL3
      and FSH or LH concentrations, which were independent of age. Taken together, the
      data show that INSL3 is an independent measure of Leydig cell function (quality
      and number), which appears to be independent of acute control via the HPG axis.
      Its decline with age reflects a decline in the properties of the Leydig cell
      population only, and emphasizes a gonadal component in the age-related decrease
      in androgen production.

PMID- 17014532
TI  - Inducible 70 kDa heat shock protein does not protect spermatogenic cells from
      damage induced by cryptorchidism.
AB  - Accumulation of inducible heat shock proteins (e.g. Hsp70i) during cellular
      stress confers thermotolerance, reduces the consequences of damage and
      facilitates cellular recovery, while abrogation of Hsp70i expression renders
      sensitivity to apoptosis. Testis translocation into abdominal cavity, which
      results in temperature elevation, does not induce expression of the Hsp70i
      proteins. Despite constitutive expression of testis-specific Hsp70 proteins,
      spermatocytes are very sensitive to damage at elevated temperatures. To test
      whether Hsp70i protein could protect testes from heat-induced damage, we have
      engineered transgenic mice that over-express this protein selectively in
      spermatocytes and spermatids. We demonstrate that the testes of cryptorchid
      transgenic mice, like those of wild-type mice, exhibit reduced weight and smaller
      sizes of their seminiferous tubules, disorganization of their germinal epithelium
      structures, appearance of multinucleated giant cells, and reduced populations of
      germ cells. The data show that constitutive expression of Hsp70i does not protect
      the seminiferous epithelium against cryptorchidism-induced damage.

PMID- 17014533
TI  - Photoperiod-induced apoptosis in the male genital tract epithelia of the golden
      hamster.
AB  - The aim of this study was to identify some details of the changes induced by a
      short-day light regime (8:16 light:dark) on the male genital tract and accessory
      sex glands of the golden hamster Mesocricetus auratus. We principally examined
      the presence of apoptotic cells in the epithelium from different regions of the
      epididymis, seminal vesicles, prostate and coagulating gland. We detected an
      increase in the percentage of apoptotic cells in situ using the TUNEL technique
      in animals that were maintained for 6, 8 or 12 weeks in a short photoperiod. That
      those cells were indeed undergoing apoptosis was confirmed by the immunodetection
      of the active fragment of caspase-3. The apoptotic indices in the different
      tissues analysed were low, but were maintained for weeks, suggesting cell loss at
      a steady rate. We tried to correlate these changes with the testosterone levels
      in serum as well as with the oxidative stress in the tissue. On the other hand,
      the increase in size and number of lipofuscin granules indicated the possibility
      that a parallel increase in oxidative stress occurred in the tissues. The
      normalization in the number of apoptotic cells and lipofuscin granules in animals
      treated with testosterone suggests that both phenomena might be related to
      changes in the hormone levels.

PMID- 17014534
TI  - Epididymal obstruction results in isolated sperm heads in post-vasectomy rats.
AB  - The aim of this study was to determine if, following vasectomy, epididymal
      obstruction resulted in changes in vasal stump fluid using a rat vasectomy model.
      One hundred and twenty-two mature male rats underwent bilateral surgical
      vasectomy and subsequent unilateral epididymal obstruction. Animals were randomly
      assigned to one of the five cohorts, which determined the time to kill and vasal
      fluid assessment. Numbers of whole sperm and sperm heads were compared between
      the obstructed and non-obstructed sides. Parametric analysis of microscopic vasal
      fluid findings was performed using a paired t-test. Whole sperm and sperm heads
      were detected bilaterally among the initial five cohorts. On the obstructed
      epididymis side, percentage of whole sperm dropped from 36.9% to less than 1% and
      sperm heads increased from 63.2 to 99.7% at 12 weeks post-obstruction (p < 0.05
      at each time interval). On the unobstructed side, percentage of whole sperm rose
      from 66.3 to 89.5% and sperm heads dropped from 33.7 to 10.5% (p < 0.05 at each
      time interval). At 12 weeks, the difference between the obstructed and non
      obstructed sides for both percentage and quantity of whole sperm and heads was
      significant with a p value of <0.001. In this rat model, following vasectomy and
      subsequent epididymal obstruction, testicular vasal stump fluid will contain
      progressively diminishing numbers of whole sperm and increases in the percentage
      and absolute numbers of sperm heads.

PMID- 17014535
TI  - The impact of malocclusion and its treatment on quality of life: a literature
      review.
AB  - AIM: The aim of this paper is to review the literature relating to the impact of
      malocclusion, and the treatment of malocclusion, on physical, social and
      psychological health (i.e. quality of life, QoL). DESIGN: English-language
      papers, including cross-sectional studies, retrospective and prospective
      longitudinal studies, randomized controlled trials, and reviews and meta-analyses
      were reviewed to determine the impact of malocclusion and its treatment on QoL.
      RESULTS: Malocclusion and its treatment can affect physical health in terms of
      pain (e.g. temporomandibular disorders, and dental and gingival trauma), speech
      and mastication. In terms of psychological health, malocclusion and its treatment
      is reported to affect self-concept. Socially, malocclusion and its treatment can
      affect perceived attractiveness by others, social acceptance and perceived
      intelligence. However, the evidence is conflicting owing to differences in study
      designs, population's studied and methods of assessment of psychical, social and
      psychological health. CONCLUSION: Much controversy exists about the impact of
      malocclusion and its treatment on QoL. There is a need for a more comprehensive
      and rigorous assessment of the impact of malocclusion and its treatment on QoL,
      employing standardized, valid and reliable data collection instruments.

PMID- 17014536
TI  - Dental health of 5-year-olds following community-based oral health promotion in
      Glasgow, UK.
AB  - AIM: A community development oral health promotion programme based on the
      principles of the Ottawa Charter was conducted in an attempt to improve the
      dental health of children under 5 years of age in two severely socioeconomically
      challenged pilot districts in Glasgow, UK. Later phased extension involved all of
      the area's most deprived communities. The aim of the present study was to assess
      dental health outcomes by secondary analysis of routine caries datasets for
      Glasgow 5-year-olds over the interval from 1997-1998 to 2003-2004. DESIGN:
      Wilcoxon tests assessed change in d3mft scores and logistic regression was used
      to analyse binomial scores (e.g. % d3mft = 0). RESULTS: After adjusting for age
      and deprivation (DepCat) in pilot districts 1 and 2, significant redistributions
      of the relative frequency of d3mft scores were observed (P = 0.012 and P < 0.001,
      respectively), mean d3mft decreased from 5.5 to 3.6 and from 6.0 to 3.6,
      respectively, and the proportions with d3mft = 0 increased from 11% to 29% and
      from 10% to 32%, respectively [P = 0.010, odds ratio (OR) = 0.25, and P = 0.006,
      OR = 0.30, respectively, for d3mft > 0]. Following extension of the programme
      into all of Glasgow's socioeconomically challenged areas, the mean d3mft values
      of 5-year-olds reduced in all DepCat 7 communities, and across Glasgow as a whole
      from 4.9 to 4.1 and from 3.5 to 3.1, respectively, while the proportion with
      d3mft = 0 increased from 20% to 32% (P < 0.001) and from 34% to 42% (P < 0.001),
      respectively. CONCLUSION: Dental health improvements were observed in pilot
      districts and across all DepCat 7 communities following the roll-out of the
      programme. This change was of sufficient magnitude to impact upon area-wide
      statistics for Glasgow.

PMID- 17014537
TI  - Effect of oral hygiene instruction and scaling on oral malodour in a population
      of Turkish children with gingival inflammation.
AB  - AIM: Oral malodour affects a large proportion of the population, and may cause a
      significant social or psychological handicap to those suffering from it. The
      condition has a positive correlation with the accumulation of bacterial plaque in
      the oral cavity. The aim of the present study was twofold: first, to determine
      whether oral malodour and periodontal disease parameters are associated with one
      another in 150 Turkish subjects (mean age +/- SD = 9.1 +/- 2.7 years; age range =
      7-12 years); and secondly, to investigate the impact of oral hygiene instruction
      and scaling on oral malodour. DESIGN: The parameters measured included whole
      mouth odour judge scoring, halimeter measurements, saliva pH scores, gingival
      index, plaque index, and probing depth before and after the treatment procedures.
      RESULTS: Odour judge scores were significantly associated with halimeter
      findings. However, gingival index, plaque index and probing depth were
      significantly associated with odour judge scores and halimeter scores. The
      statistical analysis revealed that periodontal treatments caused a significant
      reduction (P < 0.001) in volatile sulphur compound formation. CONCLUSION: These
      results suggest that, in the population studied, periodontal health and oral
      malodour are associated with one another. Oral malodour levels were significantly
      reduced after treating gingival inflammation. Thus, in order to avoid oral
      malodour in children, oral care should not be neglected.

PMID- 17014538
TI  - Validity and reliability of the Arabic translation of the child oral-health
      related quality of life questionnaire (CPQ11-14) in Saudi Arabia.
AB  - AIM: The purpose of this study was to test the validity and reliability of an
      Arabic translation and adaptation of the child oral-health-related quality of
      life questionnaire (CPQ(11-14)) in Saudi Arabia. DESIGN: The modified
      questionnaire included two global ratings (oral health and oral-health-related
      well-being), and a battery of 36 questions in four domains (oral symptoms,
      functional limitations, emotional well-being and social well-being). The study
      population consisted of 174, 11-14-year-old children (65% healthy and 35%
      medically compromised). Clinical data on caries status and malocclusion were
      collected for 138 of the children, and 47 completed the questionnaire a second
      time. RESULTS: There was a significant difference in mean total scale scores
      between children with and without malocclusions (P < 0.05). Significant
      relationships were identified between caries status and oral symptoms subscale
      scores, and between malocclusion and total scale and social well-being subscale
      scores (P < 0.05). Correlation was highly significant between scale scores and
      global ratings (P < 0.01). Cronbach's alpha was 0.81 and the test-retest
      reliability was substantial (r = 0.65, P < 0.001). However, problems were
      encountered in Saudi Arabia regarding self-reporting of age, and the
      questionnaire was too long for many of the medically compromised patients.
      CONCLUSIONS: The questionnaire is valid and reliable for use in Saudi Arabia,
      although development of a shorter version is recommended.

PMID- 17014539
TI  - The oral health and treatment needs of schoolchildren in Trinidad and Tobago:
      findings of a national survey.
AB  - OBJECTIVE: To describe the oral health and treatment need of schoolchildren in
      Trinidad and Tobago. DESIGN AND METHOD: Cross-sectional survey using stratified
      cluster sampling. Participants were children in primary (aged 6-8 years) and
      secondary school (aged 12 and 15 years). Main outcome measures were DMFT/dmft,
      treatment need, and fluorosis. RESULTS: Examinations were completed on 1064
      children. The dmft of the 6-8-year-olds was 2.54 (95% CI = 2.32, 2.76). For 12
      year-olds, the DMFT was 0.61 (95% CI = 0.51, 0.71), whereas for 15-year-olds, the
      DMFT was 1.06 (95% CI = 0.87, 1.25). Most of the caries experience in 6-8-year
      olds was from decayed teeth. Sixty-seven per cent of the sample (95% CI = 64%,
      69%) had some type of treatment need. Most frequently occurring need was for
      fillings at 42% (95% CI = 40%, 44%) with 28% (95% CI = 26%, 31%) of the total
      sample needing two or more surface fillings, followed by fissure sealants at 33%
      (95% CI = 30%, 36%) and caries-arresting care at 12% (95% CI = 10%, 14%).
      Extraction of one or more teeth was needed in 13% (95% CI = 11%, 15%) of
      children. Rates of fluorosis were negligible. CONCLUSION: The caries experience
      of 12- and 15-year-old children were low but was high for schoolchildren aged 6-8
      years, in terms of prevalence and severity. Effective oral health promotion
      strategies need to be implemented to improve the oral health of primary
      schoolchildren in Trinidad and Tobago.

PMID- 17014540
TI  - Dentinal carious lesion in three dimensions.
AB  - AIM: The aim of this study was to show the morphology of the carious lesion in
      dentine in three dimensions (3D). DESIGN: A novel high-definition X-ray
      microtomography (XMT) scanner was used to scan 10 carious primary molars at a
      resolution of 15 x 15 x 15 microm3. A stack of approximately 640 XMT slices were
      recorded for each tooth. Using this data set and a volume rendering algorithm,
      each tooth was reconstructed in 3D. The VG Studio Max 1.0 visualization software
      package was used to make normal enamel and dentine transparent to show the
      carious lesions in 3D. A video film, comprised of the rendered images from 60
      viewing angles rotating through 360 degrees , was produced to show the carious
      lesion and its relation to the pulp in a three-dimensional perspective
      (http://www.smd.qmul.ac.uk/dental/oralgrowdev/biophysics/xmt/images/carious.mpg).
      RESULTS: These images showed that carious lesions in dentine were bowl-shaped.
      The pulp adjacent to the carious lesion was also observed to mimic the base of
      the bowl-shaped lesion. CONCLUSIONS: It was concluded from the teeth studied that
      the shape at the base of the carious lesion in dentine is curved in 3D, rather
      than conical, as traditionally believed from two-dimensional image
      interpretation. Further 3D studies are needed to investigate whether the bowl
      shaped carious lesions in dentine also apply to caries in other types of teeth.

PMID- 17014541
TI  - A randomized controlled trial of the effectiveness of a one-step conditioning
      agent in sealant placement: 6-month results.
AB  - AIM: The objectives of this study were: to compare the retention of fissure
      sealants (sealants) placed on occlusal surfaces following the use of a self
      etching priming agent and traditional acid etch; to compare the caries incidence
      of occlusal surfaces sealed using the two techniques; and to compare the ease of
      placement of sealant following the use of the two techniques, as assessed by
      subjects and operators. DESIGN: The study took the form of a randomized
      controlled trial conducted in UK National Health Service community dental service
      and dental hospital clinics. Sixty subjects were recruited to this study by seven
      dental professionals who placed sealants on lower permanent molar pairs. The
      technique used for enamel preparation prior to sealant placement on the right and
      left side of the lower arch was randomized. On one side of the lower arch, Xeno
      III was used to prepare the occlusal enamel, and on the other, phosphoric acid
      etch together with Prime & Bond was used. Opaque Delton was used to seal all
      surfaces. Subjects were blinded to the techniques used. The subjects and
      operators recorded their impressions of the techniques used on individual
      questionnaires. RESULTS: Forty-six (77%) of the 60 subjects were reviewed by the
      principal researcher after 6 months. The retention of the acid-etch group was
      significantly superior (P < 0.01), as was the caries preventive effect (P <
      0.01). Subjects tended to report that placement of sealants was easier following
      enamel preparation with Xeno III (P = 0.085), and in the opinion of the
      operators, sealants were significantly easier to place when using Xeno III (P =
      0.016). CONCLUSIONS: In view of the findings of this investigation, best practice
      for the placement of sealants remains enamel preparation with acid etch and the
      use of an intermediate bonding layer.

PMID- 17014542
TI  - Major salivary gland agenesis in a young child: consequences for oral health.
AB  - BACKGROUND: Salivary gland agenesis is a rare condition. It can be associated
      with some equally rare syndromes so that diagnosis can be delayed. CASE REPORT:
      The authors describe a case report. A 3-year-old girl, presented with dry mouth,
      carious teeth, recurrent herpes labialis and tonsillitis to Newcastle Dental
      Hospital. This case highlights the diagnostic and therapeutic challenges posed by
      'salivary gland agenesis'. CONCLUSION: Primary and secondary paediatric
      healthcare professionals should be aware of the possibility of salivary gland
      agenesis in the setting of the 'non drooling baby'. Early detection of 'salivary
      gland agenesis' would do much to prevent the deleterious oral affects which
      follow the absence of salivary protection in the oral cavity.

PMID- 17014543
TI  - Extravasation mucocele involving the ventral surface of the tongue (glands of
      Blandin-Nuhn).
AB  - BACKGROUND: Mucocele is a lesion that involves the salivary glands and respective
      current ducts caused mainly by traumas in the affected area. Two different
      histological forms can be found: extravasation phenomenon and mucus-retention
      cyst where the former is the most frequently observed involving minor salivary
      glands such as the glands present in the anterior portion of the ventral surface
      of the tongue (glands of Blandin-Nuhn). CASE REPORT: This report describes a
      large lesion involving the ventral surface of the tongue that was definitively
      diagnosed by histological examination as extravasation mucocele. CONCLUSION:
      Important concepts are reviewed to help clinicians correctly diagnose and treat
      this pathology.

PMID- 17014544
TI  - Freeman-Sheldon syndrome: a case report.
AB  - BACKGROUND: Freeman-Sheldon Syndrome is a rare craniofacial syndrome that has not
      been described in the dental literature to date. The main feature of relevance is
      severe microstomia, which limits access for routine dental care. CASE REPORT:
      Dental treatment was carried out successfully under local anaesthetic for a young
      child with Freeman-Sheldon syndrome. A novel coloured compomer material was
      helpful in the management of the case. CONCLUSION: The importance of early
      referral of children with rare craniofacial anomalies to Specialist Paediatric
      Dental services is highlighted.

PMID- 17014545
TI  - Congenitally missing maxillary primary canines: report of three cases.
AB  - BACKGROUND: Hypodontia is uncommon in the primary dentition and lateral incisors
      are the most commonly missing primary teeth in the patients affected. Studies
      have found that hypodontia in the primary dentition involving only maxillary
      canine is rare. CASE REPORTS: Three cases of hypodontia in the primary dentition
      involving only maxillary canine are presented. Two of them were affected by
      hypodontia and hyperdontia in the permanent dentitions respectively, yet all the
      permanent canines developed normally in these three cases. CONCLUSION: In
      children with congenitally missing maxillary canines, the permanent dentitions
      may show diverse anomalies in tooth numbers, ranging from hypodontia to
      hyperdontia.

PMID- 17014546
TI  - Congenital double lower lip: report of a case.
AB  - A case of the management of a congenital double lower lip in a 2-week-old female
      child: is described. The mother stated that the child was having difficulties
      when suckling and was also worried about the unsightly appearance. The redundant
      lower lip was excised under general anaesthesia. The child made an uneventful
      recovery.

PMID- 17014548
TI  - Proton pump inhibitors: indigestion for nephrologists!

PMID- 17014549
TI  - Proton pump inhibitors and acute interstitial nephritis: report and analysis of
      15 cases.
AB  - AIM: Although proton pump inhibitors (PPI) are usually safe and effective
      therapeutic agents, serious adverse effects can occur. The aim of the present
      study was to report and analyse the clinical features of 15 patients with acute
      interstitial nephritis (AIN) and acute renal failure from PPI that were referred
      to renal services in Auckland over a period of 3 years. METHODS: The clinical
      presentation, therapeutic drugs, demographic details and renal outcome of the
      patients were considered. The population at risk and total PPI exposure were able
      to be defined. The diagnosis of AIN was made by renal biopsy in 12 cases. In all
      patients, the time-course of drug exposure and improvement of renal function on
      withdrawal suggested PPI were causal. RESULTS: The median patient age was 78
      years. The mean baseline serum creatinine level was 83 micromol/L, peak level 392
      micromol/L, and recovery level 139 micromol/L. The erythrocyte sedimentation rate
      (ESR) and C-reactive protein were elevated at the time of diagnosis in the 11 and
      12 patients, respectively, where this information was collected (ESR mean 85
      mm/h, and C-reactive protein mean 81 mg/L). AIN occurred at 8 per 100 000 patient
      years (95% confidence level 2.6-18.7 per 100 000 patient years). Although four
      patients presented with an acute systemic allergic reaction, 11 were asymptomatic
      with an insidious development of renal failure. CONCLUSION: PPI are now the most
      commonly identified cause of AIN in the Auckland area. Recovery occurs after
      withdrawal of the drug but is often incomplete. Early diagnosis may be
      facilitated by clinician awareness of the insidious onset of renal failure, and
      an elevated erythrocyte sedimentation rate and C-reactive protein.

PMID- 17014550
TI  - Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic
      patients receiving high-volume haemofiltration and continuous venovenous
      haemofiltration.
AB  - AIM: Sepsis is characterized by an uncontrolled release of pro-inflammatory and
      anti-inflammatory mediators leading to immunoparalysis, cellular and humoral
      dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy
      of high-volume haemofiltration (HVHF) compared with continuous venovenous
      haemofiltration (CVVH) in removing these inflammatory mediators. Clinical
      responses were assessed with the sequential organ failure assessment (SOFA)
      score. METHODS: Septic patients with an end-organ dysfunction or septic shock
      were randomized to receive 6 h of CVVH (ultrafiltration dose of 2 L/h equivalent
      to about 35 mL/kg per hour or HVHF (ultrafiltration dose of 100 mL/kg per hour or
      6 L/h, whichever was higher). The sequential organ failures were scored for the
      24 hours preceding recruitment; at day 1, day 7, at discharge from the intensive
      care unit and at hospital discharge. RESULTS: Thirty-three patients were
      enrolled. Fifteen received HVHF and 18 received CVVH. The serum IL-6 levels
      (pg/mL) at baseline were similarly elevated in both groups (P = 0.745). The HVHF
      group showed a significant reduction after 6 h of treatment with a median
      interquartile range (IQR) of 20.62 (49.21) pg/mL (P = 0.025) with no similar
      result in the CVVH group. Non-survivors showed a higher baseline serum IL-6
      compared with the survivors (median (IQR) 172.31 (261.34) vs 58.9 (104.21), P =
      0.044). In the HVHF group there was a positive association between the IL-6
      levels at 6 h with the SOFA scores at day 1 (r = 0.392, P = 0.001) but not at day
      7. After 6 h of treatment in the HVHF group there was a direct correlation
      between the IL-6 levels and number of hospital days (r = 0.90, P = 0.040). The
      maximum SOFA scores were persistently recorded before treatment. The SOFA scores
      reduced in both groups from baseline to day 7 (HVHF P = 0.048; CVVH P = 0.006).
      The SOFA scores at day 1 is significantly higher in the non-survivors compared
      with the survivors (P = 0.038). CONCLUSIONS: High-volume haemofiltration at 6 L/h
      may seem to successfully remove some inflammatory cytokines in septic patients.
      The improvement in the SOFA scores at day 7 promises benefit of continuous renal
      replacement therapy in septic patients, but after 20 days this effect may be
      lost. In addition, the baseline serum IL-6 and IL-1-ra were independent
      predictors of a poor outcome as reflected by the higher SOFA scores at day 1.

PMID- 17014551
TI  - Can acidosis and hyperphosphataemia result in increased erythropoietin dosing in
      haemodialysis patients?
AB  - AIM: To evaluate whether factors such as acidosis and hyperphosphataemia that
      might cause an increased oxygen delivery to tissues could result in increased
      dosing requirements for intravenous erythropoietin (EPO) administration given to
      haemodialysis patients. METHODS: The clinical records of the patients seen at the
      Hypertension, Nephrology, Dialysis and Transplantation Clinic from December, 2004
      through August, 2005 were reviewed to identify patients who had taken intravenous
      erythropoietin. Two-tailed, Pearson's correlation was performed to determine
      correlations between any of the parameters. Analysis of variance and stepwise
      regression for covariance were used to evaluate the relations of demographic and
      clinical characteristics and laboratory variables. Analysis of covariance and K
      means cluster analyses were also performed to examine linkage between variables.
      Kendall's Tau correlation was used for correlations of non-parametric data.
      RESULTS: There was a significant direct or positive correlation at the 0.01
      levels between dry weight, age, intact parathyroid hormone level (PTH), and serum
      phosphorus and EPO dose. There was an inverse or negative correlation at that
      level between the serum bicarbonate and urea reduction ratio (URR) with the EPO
      dose at the same level while there was a weaker correlation but direct
      correlation between the white blood count (WBC) and EPO dose. There was
      significant colinearity between serum phosphorus and PTH but serum phosphorus
      showed a more significant correlation with EPO overall. Stepwise regression
      analysis for covariance revealed that phosphorus remained significantly
      correlated with EPO resistance after the removal of the effect of PTH while PTH
      lost its significance after the effect of phosphorus was removed. CONCLUSION:
      Acidosis and hyperphosphataemia are associated with apparent increased
      erythropoietin dosing requirements. While this study did not evaluate the
      mechanism of such requirements and indeed many mechanisms might be possible, a
      rightward shift in the oxygen-haemoglobin dissociation curve resulting in down
      regulation of erythropoietin receptors is considered consistent with the data and
      present knowledge.

PMID- 17014552
TI  - Role of C-reactive protein, reticulocyte haemoglobin content and inflammatory
      markers in iron and erythropoietin administration in dialysis patients.
AB  - AIM: C-reactive protein (CRP) is an acute phase reactant protein, which becomes
      elevated in response to inflammation, infections or malignancies. These
      conditions are well known causes of bone marrow hyporesponsiveness and
      erythropoietin resistance in dialysis patients. The role of iron-deficiency as a
      cause of hyporesponsiveness under these conditions is not clear. Reticulocyte
      haemoglobin content (CHr) is one of several iron indices used to determine iron
      deficiency in dialysis patients. The aim of this study is to evaluate the role of
      CRP and CHr in iron administration and anaemia management in dialysis patients.
      METHODS: In 47 haemodialysis patients with ferritin levels of >500 ng/mL, CRP,
      CHr, transferrin saturation (TSAT), other markers and erythropoietin dose were
      evaluated. Patients with CRP < 5 mg/L (Group A) were compared to patients with
      CRP > 5 mg/L (Group B). RESULTS: Ferritin levels in the two groups were not
      different. Weekly erythropoietin was significantly different between the two
      groups. Group B required an average of 121% more erythropoietin than Group A to
      maintain similar haemoglobin levels of 11-12 g/dL 36% of Group B had CHr < 29 pg
      versus 7% of patients in Group A. 39% of patients in Group B also had TSAT < 20%
      versus 0% in Group A. Group A also had more arteriovenous (AV) fistulae as
      dialysis access than group B. CONCLUSION: Data indicate that low CHr, similar to
      low TSAT, could be associated with inflammatory process and erythropoietin
      resistance, but not necessarily with iron-deficiency. High CRP association with
      low CHr and low TSAT levels can explain the lack of response to further IV iron
      therapy. AV grafts, contrary to AV fistulae, are associated with high
      inflammatory markers and also with a higher erythropoietin requirement.

PMID- 17014553
TI  - Regional citrate anticoagulation in continuous venovenous haemofiltration using
      commercial preparations.
AB  - AIM: The aim of the present study was to test the feasibility of using commercial
      preparations of replacement and citrate anticoagulation solution in continuous
      venovenous haemofiltration (CVVH) in a safe, efficient and simple manner.
      METHODS: Retrospective review of the database of a large continuous renal
      replacement therapy programme that uses a standardized prescription of high
      ultrafiltrate CVVH with commercial solutions for replacement fluid and regional
      citrate anticoagulation was performed. RESULTS: Records of 28 patients who
      underwent 91 CVVH sessions were analysed. Median circuit survival time was 37
      (59.5-15.5) h and the 48 h survival probability was 40%. Bleeding or metabolic
      complications were not noted, and the procedure was simple to administer.
      CONCLUSION: Continuous venovenous haemofiltration using commercial preparations
      of replacement fluid and citrate anticoagulation can be safe, efficient and
      simple.

PMID- 17014554
TI  - Upper extremity arteriovenous fistula does not affect pulse oximetry readings.
AB  - AIM: Arteriovenous fistula (AVF) is usually surgically created in a patient's
      upper extremity to provide adequate blood flow during haemodialysis. Blood flow
      distal to an AVF is altered and theoretically could change pulse oximetry (SpO2)
      reading, systemic blood pressure and skin temperature. The authors conducted a
      prospective case-control study to measure changes in these parameters in the
      upper extremity of patients who have had an AVF. METHODS: In patients with an
      upper extremity AVF, the authors conducted a prospective case-control study using
      the patient's own non-AVF upper extremity as the control. The authors evaluated
      other factors that may have influenced blood flow changes distal to an AV fistula
      like gender, presence of AVF aneurysm, peripheral vascular disease, diabetes
      mellitus and vasodilator therapy. RESULTS: Thirty patients were enrolled, skin
      temperature and blood pressure were significantly altered in the hand distal to
      the AVF, but there was no significant change in the SpO2. CONCLUSION: An upper
      extremity AVF alters blood pressure and temperature measurements when compared
      with the contralateral non-AVF side, but there is no difference in SpO2 provided
      an adequate signal quality is detected.

PMID- 17014555
TI  - Comparison of biochemical, haematological and volume parameters in two treatment
      schedules of nocturnal home haemodialysis.
AB  - BACKGROUND: The biochemical, haemodynamic, clinical and nutritional benefits of
      nocturnal home haemodialysis (NHHD) compared with 4 h, three times per week
      conventional haemodialysis are well known and accrue by increasing dialysis time
      and frequency either for 8 h alternate night per week (NHHD3.5) or for 8 h six
      nights per week (NHHD6). However, there are little data comparing NHHD3.5 with
      NHHD6. METHOD AND RESULTS: Thirteen patients on NHHD6 were compared with 21
      patients on NHHD3.5, all with similar demographic profiles. Pre- and post
      dialysis phosphate (PO4) control was ideal between the groups. However, all NHHD6
      needed PO4 supplementation compared with 4/21 (19%) NHHD3.5. In the present
      study, 8/21 (38%) NHHD3.5 needed PO4 binders whereas none was required with
      NHHD6. The pre-haemoglobin (Hb) 122.8 g/L (NHHD6) versus 124.9 g/L (NHHD3.5) and
      the pre-albumin 38.31 g/L (NHHD6) versus 37.71 g/L (NHHD3.5) were not
      significantly different. NHHD6 had significantly lower pre-blood urea and
      creatinine (10.16 vs 19.54 mmol/L and 437.0 vs 812.3 micromol/L, respectively).
      Less interdialytic urea and creatinine fluctuation were also noted in NHHD6. Of
      major significance was the significantly lower ultra filtration rate and
      intradialytic weight gains (mean +/- SEM) of NHHD6 (249 +/- 76 mL/h and 2.0 +/-
      0.65 kg) versus NHHD3.5 (425 +/- 168 mL/h and 2.9 +/- 1.2 kg). CONCLUSION: The
      authors conclude that NHHD6 offers the optimum biochemical, volume and clinical
      outcome, but NHHD3.5 has additional appeal to providers seeking home-based
      therapy cost advantages and consumable expenditure control. A flexible dialysis
      programme should offer all the time and frequency options of NHHD but in
      particular, should support NHHD at a frequency sympathetic to the clinical
      rehabilitation and lifestyle aspirations of individual patients.

PMID- 17014556
TI  - Diuretics: a modern day treatment option?
AB  - The choice of drugs to initiate therapy for the management of hypertension
      remains contentious and diuretics are central to this controversy. Because most
      of the major trials involve complex treatment algorithms and allow diverse
      background treatments, one of the greatest challenges lies in separating out true
      class-specific effects - for example, separating true class-specific effects of
      diuretics from those of beta blockers. Despite these difficulties, the evidence
      confirms that diuretics are at least as effective as the newer first line groups
      in preventing cardiovascular events. The main area of doubt lies in relation to
      the risk of renal outcomes and of metabolic outcomes, such as new onset diabetes 
      where the evidence suggests that drugs that inhibit the renin-angiotensin system
      may be more protective than all other drug classes. These issues are reflected in
      the most recent international guidelines, all of which include diuretics among
      the first-line drugs for the treatment of hypertension, although they do differ
      on the role of diuretics in the initiation of therapy. Diuretics remain important
      for treating hypertension, especially in combination with other drug classes. The
      particular place of diuretics in the rank order of drugs must be tailored to suit
      the clinical situation in the individual patient. This will vary from a preferred
      option, as in black patients or elderly patients with systolic hypertension, to a
      second-line option in patients at high risk of developing new onset diabetes.

PMID- 17014557
TI  - Protein kinase C activation and its role in kidney disease.
AB  - Protein kinase C (PKC) comprises a superfamily of isoenzymes, many of which are
      activated by cofactors such as diacylglycerol and phosphatidylserine. In order to
      be capable of activation, PKC must first undergo a series of phosphorylations. In
      turn, activated PKC phosphorylates a wide variety of intracellular target
      proteins and has multiple functions in signal transduced cellular regulation. A
      role for PKC activation had been noted in several renal diseases, but two that
      have had most investigation are diabetic nephropathy and kidney cancer. In
      diabetic nephropathy, an elevation in diacylglycerol and/or other cofactor
      stimulants leads to an increase in activity of certain PKC isoforms, changes that
      are linked to the development of dysfunctional vasculature. The ability of
      isoform-specific PKC inhibitors to antagonize diabetes-induced vascular disease
      is a new avenue for treatment of this disorder. In the development and
      progressive invasiveness of kidney cancer, increased activity of several specific
      isoforms of PKC has been noted. It is thought that this may promote the kidney
      cancer's inherent resistance to apoptosis, in natural regression or after
      treatments, or it may promote the invasiveness of renal cancers via cellular
      differentiation pathways. In general, however, a more complete understanding of
      the functions of individual PKC isoforms in the kidney, and development or
      recognition of specific inhibitors or promoters of their activation, will be
      necessary to apply this knowledge for treatment of cellular dysregulation in
      renal disease.

PMID- 17014558
TI  - High glucose and advanced glycosylated end-products affect the expression of
      alpha-actinin-4 in glomerular epithelial cells.
AB  - AIM: To investigate the molecular basis for the phenotypic alterations of
      glomerular epithelial cells (GEpC, podocytes), involving cytoskeletal changes
      especially on alpha-actinin-4 as a candidate regulating the barrier to protein
      filtration and the podocyte actin cytoskeleton. METHODS: To examine the effects
      of glucose and advanced glycosylated end-products (AGE) on alpha-actinin-4, the
      author cultured rat GEpC on AGE- or BSA-coated plates under normal (5 mmol) and
      high glucose (30 mmol) conditions and examined the distribution of alpha-actinin
      by confocal microscope and measured the change in alpha-actinin-4 production by
      western blotting and reverse transcription-polymerase chain reaction. RESULTS:
      Confocal microscopy indicated that alpha-actinin-4 moved from the peripheral
      cytoplasm to inner actin filament complexes in the presence of AGE and high
      glucose. These changes might be related to the fusion of microvilli of cell
      surface examined by electron microscopy. In western blot analysis, AGE
      significantly decreased the amount of alpha-actinin by 28.1%. Furthermore, the
      combination of high glucose and AGE decreased the amount of alpha-actinin more
      significantly by 53.6% compared with that of the control. The mRNA expression for
      alpha-actinin-4 was not changed with high glucose or AGE-coated surfaces;
      however, when added, the combination of high glucose and AGE significantly
      decreased the expression of alpha-actinin-4 mRNA by 15.7% compared with that of
      the control. CONCLUSION: The author suggests that both high glucose and AGE
      (either individually or in combination) induce the cytoplasmic translocation and
      the combination suppresses the production of alpha-actinin-4 at the
      transcriptional level with post-translational modification and these in vitro
      changes may explain the cytoskeletal changes of GEpC in diabetic conditions.

PMID- 17014559
TI  - Snakebite nephropathy.
AB  - There is a broad clinical spectrum of renal involvement in snakebite. Besides the
      local and systemic symptoms, clinical renal manifestations vary from mild
      proteinuria, haematuria, pigmenturia to acute renal failure. Bites by haemotoxic
      snakes and myotoxic snakes are the common causes of renal involvement especially
      acute renal failure. Therefore, renal failure is often associated with
      haemorrhagic diathesis, intravascular haemolysis and rhabdomyolysis. Renal
      pathological changes include mesangiolysis, glomerulonephritis, vasculitis,
      tubular necrosis, interstitial nephritis and cortical necrosis. Tubular necrosis
      is an important pathological counterpart of acute renal failure. Haemodynamic
      alterations induced by cytokines and vasoactive mediators leading to renal
      ischaemia are important in the pathogenesis of acute renal failure. Haemolysis,
      intravascular coagulation and rhabdomyolysis are important contributing factors.
      Direct nephrotoxicity can be induced by the venom through metalloproteases and
      phosphilipase A2. Immunologic mechanism plays a minor role in the pathogenesis of
      the renal lesion.

PMID- 17014561
TI  - Molecular mechanisms mediating vascular calcification: role of matrix Gla
      protein.
AB  - Patients with chronic kidney disease (CKD) have a higher incidence of vascular
      calcification and a greatly increased risk of cardiovascular death. The
      mechanisms involved in the accelerated vascular calcification observed in CKD
      have recently become clearer, leading to the hypothesis that a lack of natural
      inhibitors of calcification may trigger calcium deposition. One of these
      inhibitory factors, matrix Gla protein (MGP), is the focus of the present review.
      MGP, originally isolated from bone, is a vitamin K-dependent protein that is also
      highly expressed by vascular smooth muscle cells. MGP has been confirmed as a
      calcification-inhibitor in numerous studies; however, its mechanism of action is
      not completely understood. It potentially acts in several ways to regulate
      calcium deposition including: (i) binding calcium ions and crystals; (ii)
      antagonizing bone morphogenetic protein and altering cell differentiation; (iii)
      binding to extracellular matrix components; and (iv) regulating apoptosis. Its
      expression is regulated by several factors including retinoic acid, vitamin D and
      extracellular calcium ions, and a reduced form of vitamin K (KH2) is important in
      maintaining MGP in an active form. Therefore, strategies aimed at increasing its
      expression and activity may be beneficial in tipping the balance in favour of
      inhibition of calcification in CKD.

PMID- 17014560
TI  - Combined therapy of low-dose tacrolimus and prednisone in nephrotic syndrome with
      slight mesangial proliferation.
AB  - AIM: Tacrolimus is a calcineurin inhibitor that has been increasingly used in
      transplant medicine. However, the efficacy and safety of combined therapy of low
      dose tacrolimus and prednisone in the treatment of nephrotic syndrome (NS) with
      slight mesangial proliferation has not been reported. PATIENTS AND METHODS: Sixty
      patients with NS with slight mesangial proliferation were randomly divided into a
      prednisone therapy group (control), a combined low-dose tacrolimus (2 mg/day) and
      a prednisone therapy group (tacrolimus group). The efficacy and safety of
      tacrolimus was analysed. The initial dose of prednisone was 1 mg/kg per day and
      30 mg/day in the control group and tacrolimus group, respectively. The duration
      of treatment was 6 months. RESULTS: After a 6-month trial of combined low-dose
      tacrolimus and prednisone, complete remission was achieved in 29 patients
      (96.66%) and partial remission in one patient (3.33%). In the control group,
      complete remission was achieved in 27 patients (90%) and partial remission in
      three patients (10%). A significant improvement in proteinuria levels was
      observed in the tacrolimus group compared with the control group, starting at the
      second week and remaining throughout the study period. Furthermore, a significant
      improvement in serum albumin levels was observed in the tacrolimus group compared
      with the control group, starting at the first month and remaining until the third
      month. The main side-effect was obesity (100%) and acne (46.66%) in the control
      group. However, these adverse events were not observed in the tacrolimus group.
      CONCLUSION: The results demonstrated that combined therapy of low-dose tacrolimus
      and prednisone is an effective and safe therapeutic method for NS with slight
      mesangial proliferation.

PMID- 17014562
TI  - Aldosterone breakthrough during therapy with angiotensin-converting enzyme
      inhibitors and angiotensin II receptor blockers in proteinuric patients with
      immunoglobulin A nephropathy.
AB  - BACKGROUND: We are investigating whether aldosterone breakthrough negatively
      impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE)
      inhibitors and/or angiotensin II receptor blockers (ARB). METHODS: We examine the
      role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 +/- 0.3
      g/day) outpatients (aged 41.5 +/- 10.9 years) with immunoglobulin A nephropathy
      (IgAN) accompanied by stable renal function (creatinine clearance >50 mL/min).
      The patients were treated with temocapril (1 mg; n = 14), losartan (12.5 mg; n =
      16), or a combination therapy (n = 13) for 12 months. We prospectively evaluated
      blood pressure (BP), urinary protein excretion (UPE), biochemical parameters and
      the renin-angiotensin-aldosterone system before and after 12 months of treatment.
      RESULTS: Although the overall plasma aldosterone concentrations values did not
      change after any of the treatments administered for 12 months, they eventually
      increased in 23 (temocapril, seven patients; losartan, eight patients;
      combination, seven patients) of the 43 patients (53.4%; aldosterone
      breakthrough), and fell in the remainder (46.6%). Blood pressure and renal
      function did not differ among the three groups at 12 months. In contrast, UPE was
      significantly higher in patients with, than without aldosterone breakthrough
      during temocapril and losartan administration. However, combination therapy
      induced a more remarkable reduction in UPE regardless of aldosterone
      breakthrough. CONCLUSIONS: A combination of ACE inhibitors and ARB in
      normotensive patients with IgAN produces a more profound decrease in proteinuria
      than either monotherapy. This additive antiproteinuric effect is not dependent on
      aldosterone breakthrough. Additional larger, prospective, randomized studies will
      be needed for general acceptance of this strategy.

PMID- 17014563
TI  - Early phase of reperfusion of human kidney allograft does not affect an
      erythrocyte anti-oxidative system.
AB  - BACKGROUND: Generation of reactive oxygen specimens is the basic mechanism
      leading to ischaemia/reperfusion injury of the kidney graft. Oxygen burst is a
      trigger for sophisticated biochemical changes leading to generation of oxygenated
      lipids and changes in microcirculation, which recruit recipient's neutrophils and
      contribute to delayed graft function. It has been shown that the free radicals
      generation correlates with the activity of anti-oxidative system. Superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione
      (GSH) are involved in protection against free radicals. AIM: To examine the
      activity of erythrocyte anti-oxidative system during reperfusion of the
      transplanted kidney allograft. METHODS: The study included 40 renal transplant
      recipients. Blood was taken from the iliac vein before transplantation and from
      the graft's renal vein immediately, as well as 2 and 4 min after total
      reperfusion. The authors assessed the process of reperfusion using ThermaCAM
      SC500 termovision camera. Spectrophotometric methods were used to measure
      superoxide dismutase, glutathione peroxidase and catalase activity as well as
      glutathione concentrations in erythrocytes. RESULTS: There were no statistically
      significant differences in the activities of superoxide dismutase, catalase and
      glutathione peroxidase as well as glutathione concentrations during the first 4
      min after total graft reperfusion. Nevertheless, there was a positive correlation
      between the activity of superoxide dismutase and glutathione peroxidase.
      CONCLUSION: The results suggest that the erythrocyte anti-oxidative system is
      stable during the early phase after reperfusion. An association between some anti
      oxidative enzymes was noted.

PMID- 17014564
TI  - Cardiac troponin levels in asymptomatic patients on the renal transplant waiting
      list.
AB  - AIMS: Cardiac troponin levels predict mortality and cardiovascular events in
      asymptomatic patients receiving dialysis and may be a useful clinical tool to
      stratify high-risk asymptomatic individuals. METHODS: The present study examined
      levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal
      impairment, patients receiving dialysis and renal transplant recipients. Patients
      receiving dialysis on the renal transplant waiting list were compared with those
      excluded from the list based on medical criteria. Median levels were compared
      using the Kruskal-Wallis test and proportions compared by chi-squared. RESULTS:
      Median troponin levels were higher in patients on dialysis than transplant
      recipients. Comparing patients receiving dialysis not listed compared with those
      listed for renal transplant, median cTnI levels were significantly higher (0.03
      versus 0.02 microg/L, P < 0.01) whereas median cTnT levels were not. Patients
      listed for transplantation were younger, had less clinical cardiovascular disease
      and lower C-reactive protein than those awaiting renal transplantation. The
      proportion of patients with elevated cTnT was not substantially different between
      patients awaiting renal transplantation (38%) and those excluded (52%). Levels of
      cTnI and cTnT were inversely related to renal function in predialysis and
      transplant patients, but were not related to time on dialysis for those receiving
      dialysis therapy. CONCLUSION: As patients awaiting renal transplantation are
      clinically screened for cardiovascular disease but have frequently elevated
      cardiac troponin levels, troponin may be a useful clinical tool to identify high
      risk asymptomatic patients on dialysis prior to renal transplantation. The
      influence of renal function on the interpretation of cardiac troponin and risk
      prediction requires further evaluation.

PMID- 17014565
TI  - Acute coronary syndrome in a patient with calciphylaxis.

PMID- 17014566
TI  - Acute renal failure due to myoglobulinuria in a patient struck by lightning.

PMID- 17014567
TI  - Anti-neutrophil cytoplasmic antibodies-related necrotising crescentic
      glomerulonephritis in a patient with rheumatoid arthritis.

PMID- 17014568
TI  - Effects of pyridoxine-HCl therapy on serum aminotransferase levels in
      haemodialysis patients.

PMID- 17014569
TI  - Comparison between blood exchange and classical therapy for acute renal failure
      in Weil's disease: appraisal on Thai reports.

PMID- 17014570
TI  - Colchicine myoneuropathy: the role of rhabdomyolysis.

PMID- 17014571
TI  - Renal arteriovenous malformation in a young woman presenting with haematuria and
      hypertension.

PMID- 17014573
TI  - Review article: management of patients with chronic hepatitis C virus infection
      and "normal" alanine aminotransferase activity.
AB  - BACKGROUND: Hepatitis C virus infection, a major cause of chronic liver disease,
      occurs with normal serum alanine aminotransferase activity in approximately 25%
      of patients. These patients have historically remained untreated but substantial
      evidence indicates liver damage, progression of disease and impaired quality of
      life in some individuals. AIM: To review the current management of patients with
      chronic hepatitis C and normal alanine aminotransferase activity. METHODS: This
      review represents the summary of discussions at a Clinical Workshop with a
      comprehensive literature searching of available databases (PubMed and Embase).
      RESULTS: Current limits defining normal serum alanine aminotransferase activity
      are not representative of a "healthy" status. Most patients with hepatitis C and
      normal alanine aminotransferase levels have histologically proven liver damage
      that, although generally mild, may be significant (> or =F2) in up to 20% of
      patients and progresses at approximately 50% of the rate in patients with
      elevated alanine aminotransferase levels. Some patients have persistently normal
      alanine aminotransferase activity and may have a more benign outcome, but a
      significant proportion (> or =20%) experience periods of increased serum alanine
      aminotransferase activity which may be associated with enhanced disease
      progression. CONCLUSIONS: A treatment approach that considers host and virus
      related variables and optimizes patient and cost benefits may therefore provide
      more effective management of patients with chronic hepatitis C and normal alanine
      aminotransferase activity.

PMID- 17014574
TI  - Review article: alcoholic liver disease--pathophysiological aspects and risk
      factors.
AB  - BACKGROUND: Alcoholic liver disease has a known aetiology but a complex and
      incompletely known pathogenesis. It is an extremely common disease with
      significant morbidity and mortality, but the reason why only a relatively small
      proportion of heavy drinkers progress to advanced disease remains elusive. AIM:
      To recognize the factors responsible for the development and progression of
      alcoholic liver disease, in the light of current knowledge on this matter.
      METHODS: We performed a structured literature review identifying studies focusing
      on the complex pathogenetic pathway and risk factors of alcoholic liver disease.
      Results In addition to the cumulative amount of alcohol intake and alcohol
      consumption patterns, factors such as gender and ethnicity, genetic background,
      nutritional factors, energy metabolism abnormalities, oxidative stress,
      immunological mechanisms and hepatic co-morbid conditions play a key role in the
      genesis and progression of alcoholic liver injury. CONCLUSIONS: Understanding the
      pathogenesis and risk factors of alcoholic liver disease should provide insight
      into the development of therapeutic strategies.

PMID- 17014575
TI  - Review article: immune suppression and colorectal cancer.
AB  - BACKGROUND: Advances in immunology and molecular biology have shown that
      colorectal cancer is potentially immunogenic and that host immune responses
      influence survival. However, immune surveillance and activation is frequently
      ineffective in preventing and/or controlling tumour growth. AIM: To discuss
      potential ways in which colorectal cancer induces immune suppression, its effect
      upon prognosis and avenues for therapeutic development. METHOD: A literature
      review was undertaken for evidence of colorectal cancer-induced immune
      suppression using PubMed and Medline searches. Further studies were identified
      from the reference lists of identified papers. RESULTS: Immune suppression occurs
      at a molecular and cellular level and can result in a shift from cellular to
      humoral immunity. Several mechanisms for immune suppression have been described
      affecting innate and adaptive immunity with suppression linked to poorer clinical
      outcome. CONCLUSIONS: Colorectal cancer causes direct inhibition of the host's
      immune response with a detrimental effect upon prognosis. Immunotherapy offers a
      therapeutic strategy to counteract these effects with promising results seen
      particularly in precancerous conditions and early tumours. This review strongly
      suggests that immunotherapy should be incorporated into adjuvant therapeutic
      trials for stage 2 tumours and be considered as adjuvant treatment in conjunction
      with standard chemotherapy regimes for advanced disease.

PMID- 17014576
TI  - Traditional Chinese medicine causing hepatotoxicity in patients with chronic
      hepatitis B infection: a 1-year prospective study.
AB  - BACKGROUND: Safety of traditional Chinese medicine in patients with chronic
      hepatitis B is unknown. AIM: To study the clinical outcome of traditional Chinese
      medicine-induced hepatotoxicity in chronic hepatitis B patients. PATIENTS AND
      METHODS: All chronic hepatitis B patients in 2004 with liver dysfunction
      requiring hospitalization were screened prospectively for traditional Chinese
      medicine intake. The hepatotoxicity of individual traditional Chinese medicine
      elements was determined by extensive search of both English and Chinese
      publications. RESULTS: Of 45 chronic hepatitis B patients, the liver dysfunction
      in seven (15.6%) was attributable to traditional Chinese medicine. All had liver
      dysfunction pattern resembling those of acute exacerbation of chronic hepatitis
      B. Three patients had adverse outcomes (two deaths, one liver transplantation).
      One patient had accelerated course of cirrhosis now awaiting liver
      transplantation. The identified hepatotoxic components were Polygonum multiflorum
      Thunb, Cassia obtusifolia L, Melia toosendan Sieb., Rheum palmatum L.,
      Scolopendra subspinipes mutilans L, Alisma orientale Juzepe, Glycyrrhiza
      uralensis Fisch. and Mentha haplocalyx Briq. One traditional Chinese medicine
      formula was adulterated with a highly hepatotoxic agent, N-nitrosofenfluramine.
      CONCLUSIONS: Traditional Chinese medicine-related hepatotoxicity resulted in high
      mortality in chronic hepatitis B patients. Prospective randomized-controlled
      trials with the same stringent criteria as western medicine clinical trials are
      required for Chinese medicines, to document their efficacies and safety before
      they can be advocated for the treatment of patients.

PMID- 17014577
TI  - Drug-induced liver injury in a Swedish University hospital out-patient hepatology
      clinic.
AB  - BACKGROUND: Limited data exist on the proportion of drug-induced liver injury
      among out-patients seen in a hepatology clinic. AIM: To determine the proportion
      of drug-induced liver injury cases, and identify the most important agents and
      the nature of the liver injury. METHODS: A computerized diagnoses database in an
      out-patient hepatology clinic in a Swedish University hospital was analysed
      during the period 1995-2005. All suspected drug-induced liver injury cases were
      causality assessed with the International Consensus Criteria. RESULTS: A total of
      1164 cases were seen for the first time during this period. Drug-induced liver
      injury with at least a possible causal relationship was found in 77 cases (6.6%),
      38 (3.3%) of whom were referred for evaluation to the out-patient clinic whereas
      3% had a follow-up after hospitalization of drug-induced liver injury. The median
      age was 58 years, 43 (56%) were females, a hepatocellular pattern was observed in
      37 cases (48%), cholestatic in 31 (40%) and mixed in 12%. Antibiotics were the
      most common agents causing drug-induced liver injury followed by non-steroidal
      anti-inflammatory drugs, with diclofenac most often responsible for the drug
      induced liver injury. CONCLUSIONS: Drug-induced liver injury cases constituted 6%
      of all out-patients and 3% of referrals and occurred more often in women.
      Antibiotics and diclofenac were the most common causes of drug-induced liver
      injury among out-patients.

PMID- 17014578
TI  - Persistent elevation of serum alanine aminotransferase levels leads to poor
      survival and hepatocellular carcinoma development in type 1 autoimmune hepatitis.
AB  - BACKGROUND: Although the prognosis of type 1 autoimmune hepatitis is generally
      good with immunosuppressive treatment, the disease progresses in some patients
      despite the treatment. The prognosis may be determined by the clinical course.
      AIM: To evaluate the long-term prognosis and assess the predictive factors for a
      serious event, including the development of hepatocellular carcinoma or death.
      METHODS: Sixty-nine patients with type 1 autoimmune hepatitis were prospectively
      followed up regularly, with a median follow-up period of 96 months (49-201
      months). RESULTS: During the follow-up period, three patients (4%) developed
      hepatocellular carcinoma, and two of these three patients died. Another patient
      died of liver failure. The 10-year survival rate was 98%, and the 10-year
      hepatocellular carcinoma-free rate was 93%. The four patients experiencing a
      serious event received higher maintenance doses of corticosteroid during their
      follow-up periods than those did not. However, serum alanine aminotransferase
      levels during the follow-up period were higher in these four patients than in the
      others. CONCLUSIONS: Persistent elevation of serum alanine amniotransferase
      levels during the follow-up period, rather than factors existing prior to medical
      treatment is considered to be an important prognostic factor, and it is indicated
      that poor outcomes may result from the resistance to immunosuppressive treatment.

PMID- 17014579
TI  - Effects of phlebotomy therapy on cytochrome P450 2e1 activity and oxidative
      stress markers in dysmetabolic iron overload syndrome: a randomized trial.
AB  - AIM: To assess the effects of iron removal on cytochrome P450 2E1 activity and
      oxidative stress in dysmetabolic iron overload syndrome. METHODS: Forty-eight
      patients were randomized to phlebotomy therapy consisting of removal of 300-500
      mL of blood every 14 days until serum ferritin levels dropped under 100 microg/L
      or to follow-up without phlebotomy therapy. Cytochrome P450 2E1 activity was
      measured at baseline and at the end of treatment by using the 6
      hydroxychlorzoxazone/chlorzoxazone blood metabolic ratio, 2 h after the intake of
      500 mg of chlorzoxazone. RESULTS: In the treatment group, a mean of 3.9 +/- 1.3 L
      of blood was removed and serum ferritin levels dropped from 715 +/- 397 to 74 +/-
      34 microg/L. Variation of cytochrome P450 2E1 activity was not significantly
      different between the 2 groups (0.07 +/- 0.26 vs. 0.03 +/- 0.19, P = 0.36). In
      the treatment group, low-density lipoprotein cholesterol and vitamin E were
      lowered after treatment compared with control group (-0.15 +/- 0.51 vs. 0.24 +/-
      0.58, P = 0.002 and -1.3 +/- 4.4 vs. 2.3 +/- 5.2, P = 0.03, respectively).
      Inversely, vitamin C was increased (0.5 +/- 3.5 vs. -1.8 +/- 3.9, P = 0.03).
      CONCLUSIONS: In dysmetabolic iron overload syndrome, reduction of iron stores
      does not significantly influence cytochrome P450 2E1 activity but is associated
      with a significant decrease of low-density lipoprotein cholesterol, suggesting
      that venesection therapy may be a suitable option in these patients.

PMID- 17014580
TI  - Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is prevalent in affluent countries
      and is strongly associated with metabolic syndrome. AIM: To study the prevalence
      of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with
      non-alcoholic fatty liver disease. METHODS: 73 consecutive patients with biopsy
      proven non-alcoholic fatty liver disease and no history of diabetes underwent
      comprehensive metabolic screening. Diagnosis of diabetes and impaired glucose
      regulation was based on the 2006 American Diabetes Association criteria. RESULTS:
      The prevalence of undiagnosed diabetes and impaired glucose tolerance in non
      alcoholic fatty liver disease patients was 33% and 29%, respectively. Among
      patients with 2-h plasma glucose above 7.8 mm, 47% had normal fasting glucose
      (below 5.6 mm). Impaired glucose tolerance was more common in patients with non
      alcoholic steatohepatitis than those with simple hepatic steatosis (P = 0.036),
      and 2-h plasma glucose correlated with fibrosis stage (Spearman coefficient:
      0.25, P = 0.046). In a binary logistic regression analysis, high fasting glucose
      and low high-density lipoprotein cholesterol were independent factors associated
      with diabetes. Nevertheless, if oral glucose tolerance test was only performed in
      non-alcoholic fatty liver disease patients with impaired fasting glucose, 20.8%
      of diabetes cases would be missed. CONCLUSIONS: Isolated postchallenge
      hyperglycaemia is common among Chinese non-alcoholic fatty liver disease patients
      without history of diabetes. It is associated with histological severe disease,
      and cannot be accurately predicted by any fasting glucose cut-off.

PMID- 17014581
TI  - Impact on adherence and sustained virological response of psychiatric side
      effects during peginterferon and ribavirin therapy for chronic hepatitis C.
AB  - BACKGROUND: The psychiatric side effects of interferon, often responsible for
      dose reduction or treatment discontinuation, represent a major limitation in the
      treatment of chronic hepatitis C (CHC). AIM: To prospectively assess the impact
      on adherence and sustained virological response (SVR) of the occurrence of
      psychiatric side effects during peginterferon and ribavirin therapy for CHC.
      METHODS: Ninety-eight consecutive treatment-naive CHC patients receiving a
      standard course of peginterferon plus ribavirin were systematically screened for
      psychiatric side effects, using DSM-IV, at baseline and both during and after
      treatment. RESULTS: Psychiatric side effects occurred in 38 patients (39%),
      mostly within the first 12 weeks (87%), and always consisted of mood disorders.
      Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and
      68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did
      not differ between patients with mood disorders and those without (46% vs. 37%,
      respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral
      therapy had to be discontinued in four patients (nonresponse: two,
      hyperthyroidism: one, psychiatric event: one). CONCLUSION: Early detection and
      appropriate management of psychiatric side effects during peginterferon and
      ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

PMID- 17014582
TI  - Survival and dependence on home parenteral nutrition: experience over a 25-year
      period in a UK referral centre.
AB  - BACKGROUND: Home parenteral nutrition (HPN) is the standard treatment for severe
      intestinal failure in the United Kingdom. AIM: To review long-term survival and
      ongoing HPN dependence of patients receiving HPN treated at a specialist UK
      referral centre. METHODS: Medical records of patients commenced on HPN between
      1979 and 2003 were reviewed retrospectively. Regression analysis was employed to
      identify factors associated with poor prognosis. RESULTS: Case notes of 188
      patients were reviewed. Overall probability of survival was 86%, 77%, 73% and 71%
      at 1, 3, 5 and 10 years after starting treatment. In multivariate analysis,
      association was seen between mechanism of intestinal failure and survival: short
      bowel syndrome associated with a favourable prognosis, and intestinal
      dysfunction, dysmotility and obstruction with poorer prognoses. There was an
      association between increasing age and poor prognosis, but increased mortality
      was also seen in the youngest age groups. Only 9% of deaths were due to
      complications of HPN. Continued HPN dependence was 89%, 87%, 84% and 84% at 1, 3,
      5 and 10 years in survivors. CONCLUSIONS: Long-term survival of patients
      receiving HPN remains better than that reported after intestinal transplantation.
      Mortality predominantly relates to underlying disease rather than complications
      of HPN.

PMID- 17014583
TI  - A prospective 1-year follow-up study in patients with functional or organic
      dyspepsia: changes in gastrointestinal symptoms, mental distress and fear of
      serious illness.
AB  - BACKGROUND: Psychosocial factors are common among patients with functional
      gastrointestinal disorders (FGIDs). Whether they affect the course of the disease
      remains unresolved. AIM: To evaluate whether reassuring investigations of primary
      care patients with functional dyspepsia (FD) and organic dyspepsia (OD) influence
      gastrointestinal (GI) symptoms and psychological factors, and to assess whether
      these changes are correlated. METHODS: Four hundred consecutive patients with
      dyspepsia were referred for thorough examinations. Patients completed
      questionnaires screening symptoms at baseline and on 1-year follow-up. RESULTS:
      At baseline, there was no difference in GI symptoms, prevalence of mental
      distress or fear of serious illness between patients with FD or OD. On follow-up,
      the patients with FD had more GI symptoms, but there was no difference in mental
      distress or fear of serious illness. Relevant GI symptom reduction related to
      alleviation of mental distress (53.4% vs. 20.5%, P < 0.001) and fear of serious
      illness (56.5% vs. 23.7%, P = 0.002), but reached statistical significance only
      in patients with OD. CONCLUSIONS: Gastrointestinal symptoms in FD patients are
      long lasting compared with those with organic diseases. Reassuring investigations
      could lower mental distress and fear of serious illness in these patients.
      Psychological factor change correlates with the change in GI symptom severity and
      is not specific to FGIDs.

PMID- 17014584
TI  - Pre-endoscopic proton pump inhibitor therapy reduces recurrent adverse
      gastrointestinal outcomes in patients with acute non-variceal upper
      gastrointestinal bleeding.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce
      rebleeding rates in patients with high-risk acute non-variceal upper
      gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy,
      although its incremental benefit is unproven. AIM: To determine if providing PPIs
      before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal
      upper gastrointestinal bleeding patients. METHODS: We performed a retrospective
      review to identify patients presenting to two tertiary care centres with acute
      non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects
      receiving PPI therapy before endoscopy were compared with those not receiving pre
      endoscopic PPI therapy. The primary outcome measure was the development of any
      adverse bleeding outcome (rebleeding, surgery for control of bleeding, in
      hospital mortality, readmission within 30 days for acute non-variceal upper
      gastrointestinal bleeding). RESULTS: 385 patients were included in our study [132
      (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI].
      Patients receiving pre-endoscopic PPI therapy were significantly less likely to
      develop adverse outcomes compared with those not given pre-endoscopic PPIs (25%
      vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and
      length of hospital stay were also significantly lower in patients receiving pre
      endoscopic PPI. CONCLUSIONS: The use of PPIs before endoscopy significantly
      reduces the risk of developing adverse gastrointestinal outcomes in patients with
      acute non-variceal upper gastrointestinal bleeding. Future studies are required
      to better characterize this relationship.

PMID- 17014585
TI  - Serum bilirubin and risk of colorectal cancer.

PMID- 17014587
TI  - CagA status and successful eradication of Helicobacter pylori.

PMID- 17014589
TI  - Motor disturbances participate in the pathogenesis of eosinophilic oesophagitis,
      beyond the fibrous remodelling of the oesophagus.

PMID- 17014592
TI  - Problem-solving therapy for pain in the older adult.

PMID- 17014593
TI  - Debate that strengthens: evaluating new technologies in pain medicine.

PMID- 17014594
TI  - Pain scores: are the numbers adding up to quality patient care and improved pain
      control?

PMID- 17014595
TI  - Duloxetine for patients with diabetic peripheral neuropathic pain: a 6-month open
      label safety study.
AB  - OBJECTIVE: Duloxetine is a relatively balanced and potent reuptake inhibitor of
      both serotonin and norepinephrine. Because these neurotransmitters play a role in
      pain inhibition, duloxetine was considered a possible treatment for diabetic
      peripheral neuropathic pain (DPNP). This study assessed the 6-month safety and
      tolerability of duloxetine in patients with DPNP; evaluation of efficacy was a
      secondary objective. DESIGN: In this 28-week, open-label study, in the clinical
      setting, 449 patients with DPNP were randomized (3:1) to receive duloxetine 60 mg
      twice daily (BID) (N = 334) or duloxetine 120 mg once daily (QD) (N = 115).
      Comprehensive safety evaluations including laboratory analyses and
      electrocardiograms were performed for all patients. Efficacy measures included
      the Brief Pain Inventory (BPI) and Clinical Global Impression of Severity (CGI-S)
      scales. RESULTS: Protocol completion rates were 63.8% and 62.6% for the 60 mg BID
      and 120 mg QD groups, respectively (P = 0.823). Discontinuations were primarily
      due to adverse events, 20.1% for 60 mg BID and 27.0% for 120 mg QD (P = 0.149).
      Heart rate increased slightly in both treatment groups (P </= 0.02 in both
      groups). Systolic blood pressure was unaffected, while diastolic blood pressure
      decreased slightly in the 120 mg QD group (P = 0.04). Sustained elevation in
      blood pressure was reported for 18 (5.5%) patients in the 60 mg BID group and six
      (5.4%) in the 120 mg QD group. Duloxetine treatment was not associated with
      significant QTc prolongation. There was significant improvement at endpoint on
      all subscales of the BPI and CGI-S (P < 0.001 in both groups). CONCLUSIONS: In
      this study, duloxetine 60 mg BID and 120 mg QD were safely administered and well
      tolerated in patients with DPNP for up to 28 weeks. There were few differences in
      safety or tolerability between the two dosages. At both doses, duloxetine
      provided clinically significant pain relief.

PMID- 17014596
TI  - Botulinum toxin--a treatment for migraine? A systematic review.
AB  - Scalp injection of botulinum toxin type A (BT-A) into the superficial musculature
      has evoked interest in the management of migraine headache. In clinical trials,
      prevention of migraine attacks for 3 months or more has been seen in some
      patients following BT-A scalp injections. In the majority of pain syndromes where
      BT-A is effective, inhibition of muscle spasms appears to be an important
      component of its activity. A direct or independent and prolonged analgesic action
      unrelated to skeletal muscle relaxation is believed to underlie the prophylactic
      efficacy of BT-A in migraine; peripheral and central modulation of pain impulses
      by BT-A has also been proposed. A direct peripheral antinociceptive effect was
      not seen in three controlled studies of BT-A in normal human volunteers.
      Experimental evidence for BT-A-induced analgesia in rats is suggestive but dose
      dependent and lasts only 2 weeks. In migraine patients, a consistent or dose
      dependent response to BT-A treatment has not been seen. Peak responses to BT-A in
      migraine patients are seen at 8-12 weeks, whereas BT-A-affected nerve endings in
      mice fully recover function between 63 and 91 days; the difference in species
      limits the interpretation of this dissonance. As BT-A does not normally cross the
      intact blood-brain barrier, meningeal nociceptors appear unlikely to be
      influenced by scalp injections of BT-A; the possibility of antidromic transfer of
      BT-A in the trigeminovascular system should be considered. The extended period
      for which migraine prophylaxis might be required, the antigenic and headache
      provoking potential of BT-A, the inability of BT-A to affect central neuronal
      processes significantly, including the aura of migraine, the possible placebo
      effect of needling, and purely subjective outcome measures in headache studies
      are additional concerns in evaluating this treatment strategy. The clinical
      utility of BT-A has not been compared against established migraine prophylactic
      agents. The efficacy of BT-A in preventing migraine headache attacks remains
      controversial and the underlying scientific rationale is debatable.

PMID- 17014597
TI  - PRF: too good to be true?

PMID- 17014598
TI  - Pulsed radiofrequency.

PMID- 17014599
TI  - Pulsed radiofrequency treatment: what is the evidence of its effectiveness and
      should it be used in clinical practice?

PMID- 17014600
TI  - Pulsed radiofrequency: current clinical and biological literature available.
AB  - OBJECTIVE: Pulsed radiofrequency, where short bursts of radiofrequency energy are
      applied to nervous tissue, has been used by pain practitioners as a non- or
      minimally neurodestructive technique, alternative to radiofrequency heat lesions.
      Clinical advantages and mechanisms of this treatment remain unclear. The
      objective of this study was to review current clinical and laboratory data.
      DESIGN: We systematically searched the MEDLINE database (PubMed) and tables of
      contents of electronically available pain journals. Reference lists of relevant
      reports and international scientific pain congress abstract books were also hand
      searched. Only those reports on pulsed radiofrequency were withheld. RESULTS: The
      final analysis yielded 58 reports on the clinical use of pulsed radiofrequency in
      different applications: 33 full publications and 25 abstracts. We also retrieved
      six basic science reports, five full publications, and one abstract. CONCLUSIONS:
      The accumulation of these data shows that the use of pulsed radiofrequency
      generates an increasing interest of pain physicians for the management of a
      variety of pain syndromes. Although the mechanism of action has not been
      completely elucidated, laboratory reports suggest a genuine neurobiological
      phenomenon altering the pain signaling, which some have described as
      neuromodulatory. No side effects related to the pulsed radiofrequency technique
      were reported to date. Further research in the clinical and biological effects is
      justified.

PMID- 17014601
TI  - Intradiscal high-voltage, long-duration pulsed radiofrequency for discogenic
      pain: a preliminary report.
AB  - BACKGROUND: Intradiscal radiofrequency, with the electrode placed in the center
      of the nucleus pulposus, has been a controversial procedure in patients with
      discogenic pain. Possibly the effect has not been due to the production of heat,
      but to exposure to electric fields. DESIGN: We have investigated the effect of
      high-voltage, long-duration intradiscal pulsed radiofrequency in patients with
      one-level discogenic low back pain, as confirmed by discography. OUTCOME MEASURE:
      The pain intensity score on a 0-10 numeric rating scale (NRS) was taken as
      outcome measure. PATIENTS: Eight patients were reported. The mean duration of
      pain was 6.3 years (range 0.5-16, median 4). The mean NRS score was 7.75 (range 5
      9). Disc height was reduced 60% in one patient and up to 30% in the others.
      INTERVENTION: A 15-cm, 20-gauge needle with a 15-mm active tip was placed
      centrally in the disc. Pulsed radiofrequency was applied for 20 min at a setting
      of 2 x 20 ms/s and 60 V. RESULTS: There was a very significant fall in the NRS
      scores over the first 3 months (P < 0.0001). On an individual basis, all patients
      had a fall of the NRS score of at least 4 points at the 3-month follow-up. A
      follow-up of 12.8 months (range 6-25, median 9) was available for five patients.
      All these patients are now pain free, except for one patient with an NRS score of
      2. Conclusion. It is concluded that this method merits a controlled, prospective
      study.

PMID- 17014602
TI  - Pulsed radiofrequency denervation for the treatment of sacroiliac joint syndrome.
AB  - OBJECTIVE: Current therapies for sacroiliac joint (SIJ) dysfunction offer
      discouraging results in alleviating low back pain. The innervation and target
      nerves for radiofrequency denervation (RFD) of the SIJ remain unclear. We present
      a prospective case series on the treatment of intractable SIJ dysfunction with
      pulsed radiofrequency denervation (PRFD) of lateral branches from L4-S3.
      INTERVENTIONS: A total of 126 patients with presumptive SIJ dysfunction based on
      history and physical examination underwent arthrographically confirmed
      steroid/local anesthetic SIJ injection. Fifty-two patients (41.3%) had >75% pain
      relief after two consecutive injections, physical therapy, repeated SIJ
      injections, and/or analgesics. Twenty-two patients failed to respond. These
      patients underwent PRFD of the medial branch of L4, posterior primary rami of L5,
      and lateral branches S1 and S2. OUTCOME MEASURES: Visual analog score (VAS) and
      quality of life (QOL) assessments were performed prior to and after treatment.
      RESULTS: Sixteen patients (72.7%) experienced "Good" (>50% reduction in VAS), or
      "Excellent" (>80% reduction in VAS) pain relief following PRFD. Duration of pain
      relief range was 6-9 weeks in four patients, 10-16 weeks in five patients, and 17
      32 weeks in seven patients. In addition, QOL scores improved significantly in all
      measured categories. Six patients (26.1%) did not respond to PRFD and had less
      than 50% reduction in VAS and were considered failures. CONCLUSIONS: PRFD of the
      lateral branch of the medial branch of L4, posterior primary rami of L5, and
      lateral branches S1 and S2 is an effective treatment for some patients with SIJ
      pain unresponsive to other forms of therapy.

PMID- 17014603
TI  - Pulsed radiofrequency treatment of the lumbar medial branch for facet pain: a
      retrospective analysis.
AB  - BACKGROUND: The use of pulsed radiofrequency (PRF) for treatment of the medial
      branch is controversial. STUDY DESIGN: A retrospective study of the results of
      PRF treatment of the medial branch in 48 patients with chronic low back pain was
      carried out. Patients who did not respond were offered treatment with
      conventional radiofrequency heat lesions. PATIENT MATERIAL: Patients were
      included who had low back pain and >50% pain relief following a diagnostic medial
      branch block. The mean age was 53.1 +/- 13.5 years, the mean duration of pain was
      11.4 +/- 10.9 years (range 2-50). Nineteen patients had undergone surgery.
      METHODS: Pain scores on a numeric rating scale of 1-10 were noted before and
      after the diagnostic nerve block, before the procedure, and at 1-month and 4
      month follow-up. PRF was applied for 2 minutes at a setting of 2 x 20 ms/s and 45
      V at a minimum of two levels using a 22G electrode with a 5 mm active tip. Heat
      lesions were made at 80 degrees C for 1 minute. OUTCOME DEFINITION: A successful
      outcome was defined as a >60% improvement on the numeric rating scale at 4-month
      follow-up. RESULTS: In 21/29 nonoperated patients and 5/19 operated patients, the
      outcome was successful. In the unsuccessful patients who were subsequently
      treated with heat lesions, the success rate was 1/6. CONCLUSION: The setup of our
      study does not permit a comparison with the results of continuous radiofrequency
      (CRF) for the same procedure, other than the detection of an obvious trend. When
      comparing our results with various studies on CRF of the medial branch such a
      trend could not be found. Based on these retrospective data, prospective and
      randomized trials, for example, radiofrequency vs PRF are justified.

PMID- 17014604
TI  - Spinal cord stimulation is an effective treatment for the chronic intractable
      visceral pelvic pain.
AB  - OBJECTIVE: Recent studies have demonstrated significant involvement of dorsal
      column pathways in transmission of visceral pelvic pain. Spinal cord stimulation
      (SCS) suppresses visceral response to colon distension in an animal model and
      therefore may be an effective therapy for chronic pelvic pain of visceral origin.
      We are reporting on the value of neurostimulation for chronic visceral pelvic
      pain in six female patients with the diagnosis of long-standing pelvic pain
      (history of endometriosis, multiple surgical explorations, and dyspareunia).
      DESIGN AND SETTINGS: Case-series report. All patients received repeated
      hypogastric blocks (in an average of 5.3 blocks) with a significant pain relief
      for a period ranging from 1 to 6 weeks. Three received neurolytic hypogastric
      block with the pain relief of 3, 8, and 12 months, respectively. Following
      psychological evaluation and clearance by our Multidisciplinary Committee on
      Implantable Devices, they all underwent SCS trial for 7-14 days. All patients
      received SCS systems with dual leads (Compact or Quad leads, Medtronic Inc.,
      Minneapolis, MN, USA). RESULTS: The average follow-up was 30.6 months. Median
      visual analog scale pain score decreased from 8 to 3. All patients had more than
      50% of the pain relief. Pain Disability Index changed from an average of 57.7 +/-
      12 to 19.5 +/- 7. Opiate use decreased from an average 22.5 mg to 6.6 mg of
      morphine sulfate milligram equivalents per day. CONCLUSION: It appears that SCS
      may have a significant therapeutic potential for treatment of visceral pelvic
      pain.

PMID- 17014606
TI  - A case of pulsed radiofrequency lesioning for occipital neuralgia.
AB  - OBJECTIVE: This report describes a case where pulsed radiofrequency lesioning
      (RFL) of the greater occipital nerve (GON) offered a valuable and safe treatment
      for the management of greater occipital neuralgia. The case is considered in
      relation to a review of the medical literature on greater occipital neuralgia and
      RFL interventions. CASE REPORT: A 62-year-old man with a 43-year history of left
      suboccipital pain underwent pulsed RFL of the left GON (20-millisecond bursts at
      intervals of 0.5 second for 4 minutes at 42 degrees C) after failing to achieve
      substantial analgesia with naproxen, a transcutaneous electrical nerve stimulator
      (TENS) unit and a greater occipital nerve blockade (GONB) utilizing local
      anesthetic and steroid. After obtaining 4 months of 70% pain relief, pulsed RFL
      was repeated and resulted in an additional 5 months of 70% pain relief.
      CONCLUSIONS: Pulsed RFL of the GON is an alternative to continuous RFL with the
      proposed advantage of mitigating pain, as in continuous RFL, but without the
      potential risk of causing deafferentation pain. While placebo and other
      nonspecific analgesic effects cannot be ruled out, the apparent safety profile
      and potential efficacy of pulsed RFL suggests it may be a compelling option to
      consider before irreversible neuroablative therapies are applied.

PMID- 17014607
TI  - Interventional pain medicine: financial success and ethical practice: an
      oxymoron?

PMID- 17014605
TI  - The relationship between pain and mental flexibility in older adult pain clinic
      patients.
AB  - OBJECTIVE: Persistent pain and cognitive impairment are each common in older
      adults. Mental flexibility, memory, and information-processing speed may be
      particularly vulnerable in the aging brain. We investigated the effects of
      persistent pain on these cognitive domains among community-dwelling, nondemented
      older adults. SETTING: Older Adult Pain Management Program. DESIGN: A total of 56
      new patients (mean age 76.1 years) were recruited to describe 1) rates of
      persistent pain conditions and pain intensity; 2) cognition (mental flexibility,
      short-term memory, and psychomotor speed); 3) severity of depression; and 4)
      sleep quality. All patients had nonmalignant pain for at least 3 months. Pain
      intensity was measured with the McGill Pain Questionnaire and depression severity
      with the 17-item Hamilton Rating Scale for Depression. Cognition was assessed
      with 1) Mini-Mental State Exam; 2) Number-Letter-Switching and Motor Speed
      subtests of the Delis-Kaplan Executive Function System Trail Making Test; 3)
      Digit Symbol Subtest (DSST) of the Wechsler Adult Intelligence Scales-III; and 4)
      free and paired recall of the DSST digit-symbol pairs. Multiple linear regression
      modeled whether these variables predicted poorer cognitive outcomes, after
      adjusting for the effects of opioids, sleep impairment, depression, medical
      comorbidity, and years of education. RESULTS: In univariate analysis, pain
      severity was associated with a greater impairment on number-letter switching (r =
      -0.42, P = 0.002). This association remained after adjusting for the effects of
      depression, sleep, medical comorbidity, opioid use, and years of education (t = 
      1.97, P = 0.056). CONCLUSIONS: In community dwelling older adults, neither pain
      nor mood was associated with measures of short-term memory or information
      processing speed. However, pain severity was associated with decreased
      performance on a test of number-letter switching, indicating a relationship
      between pain and mental flexibility.

PMID- 17014608
TI  - The treating physician as expert witness: ethical and pragmatic considerations.
AB  - OBJECTIVE: The objective of this analysis is to apprise pain physicians of the
      ethical concerns and practical considerations that arise when a treating
      physician is called upon to testify as an expert witness in a legal proceeding
      involving his or her own patient. The provision of expert testimony in medico
      legal proceedings has come under heightened scrutiny in recent years. When a
      physician testifies as an expert witness, such testimony is considered to be the
      practice of medicine, and hence subject to the same ethical and professional
      obligations as patient care. Increasingly, medical professional organizations
      have promulgated guidelines for such activities, and even implemented oversight
      mechanisms to review complaints concerning expert testimony by their members.
      Additional issues are raised when the expert witness is also the treating
      physician for the patient who is a party to the legal proceeding in which the
      expert testimony is offered. CONCLUSIONS: While it is not categorically unethical
      or inadvisable for a physician to testify as an expert witness in a medico-legal
      proceeding involving his or her own patient, such activity raises special issues
      and concerns. Prospective expert witnesses in such situations should be cognizant
      of these issues and insure that they have been adequately addressed before and
      during the testimony.

PMID- 17014609
TI  - Conflicts of interest with the health industry.

PMID- 17014620
TI  - The vitamin D slant on allergy.
AB  - Oral vitamin D supplementation has been introduced into modern medicine to
      prevent rickets without the knowledge that this may have profound immunological
      consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell
      maturation and consecutive Th(1) cell development, which has independently
      described as a key mechanism of allergy development. Animal studies and
      epidemiological surveys now provide a first link of early vitamin D
      supplementation and later allergy where several vitamin D regulated genes seem to
      be involved. A randomized clinical trial of vitamin D supplementation could be a
      further step to follow up the vitamin hypothesis.

PMID- 17014621
TI  - Relationship between maternal- and fetal-specific IgE.
AB  - AIM: A positive correlation between maternal and cord-blood IgE levels is well
      documented for total IgEs, but not for specific IgEs. The difficulty in detecting
      specific cord-blood IgEs is due to their low concentrations, which hinder their
      dosage by low-sensitivity methods. The study aimed to correlate maternal and
      foetal specific IgEs against individual cow's milk proteins, detected by highly
      sensitive and specific techniques. METHODS: Cow's milk specific IgE detection was
      performed by chemiluminescence on 52 specimens of maternal and cord blood after
      cow's milk protein separation by 1D and 2D gel electrophoresis. Cow's milk
      protein (CMP) antigens were identified by mass spectrometry techniques. RESULTS:
      Specific IgEs for CMPs were found in 25/52 (48.1%) of maternal sera and in 19/52
      (37%) of cord-blood sera. In order of decreasing frequency, the proteins found
      were BSA, IgG heavy chain, caseins and, in a single case, b-lactoglobulin.
      Positive cord-blood sera in all cases corresponded to a positive maternal result,
      and maternal and foetal immunoreactivity patterns were closely correlated.
      Moreover, in no case was there a positive cord-blood response with a negative
      maternal response. CONCLUSION: The study demonstrates a close relationship
      between maternal and cord-blood specific IgE patterns. The phenomenon observed
      could provide a model to elucidate the general production method of foetal IgEs,
      which might only be produced in the presence of both the corresponding maternal
      IgE and the related allergen.

PMID- 17014622
TI  - Association between cord blood IgE and genetic polymorphisms of interleukin-4,
      the beta-subunit of the high-affinity receptor for IgE, lymphotoxin-alpha, and
      tumor necrosis factor-alpha.
AB  - High cord blood immunoglobulin E (cbIgE) is known to be associated with increased
      risks of atopic diseases in childhood. The relationship between genetic
      polymorphisms and high cbIgE has not been well documented. A cross-sectional
      study was conducted to assess the association between cbIgE and genetic
      polymorphisms of interleukin (IL)-4 -590C/T, the beta-subunit of the high
      affinity receptor for IgE (FcepsilonRI-beta) E237G, lymphotoxin (LT)-alphaNcoI
      alleles, and tumor necrosis factor (TNF)-alpha -308G/A. A total of 320 mother
      neonate pairs were recruited from four maternity hospitals from different
      locations of Taiwan. Cord blood was obtained and assayed for cbIgE. Polymerase
      chain reaction followed by restriction fragment length polymorphism was used to
      assess the genotypes. Three hundred pairs of mothers and neonates were included
      in the final analysis. Infants with IL-4 -590 C allele were found to have higher
      risk of elevated cbIgE (> or =0.35 IU/ml, 24.3%) (p = 0.004). After adjusting for
      gender, birth order, maternal age, and history of allergic disease in maternal
      and paternal families, odds ratios for CC and CT genotypes were 4.41 and 3.16
      (95% confidence interval 0.78-22.67, and 1.66-6.13), respectively, using TT
      genotype as reference. The genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha
      were not associated with cbIgE before or after the adjustment. Our finding
      suggested a significant association of cbIgE with genetic polymorphism of IL-4 
      590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha.

PMID- 17014623
TI  - CC chemokine receptor expression in childhood asthma is influenced by natural
      allergen exposure.
AB  - Chemokines and their receptors may play an important role for leukocyte
      trafficking in allergic inflammation. Aim was to evaluate whether expression of
      chemokine receptors CCR4 and CCR8 on cells obtained by sputum induction from
      asthmatic allergic children may be influenced by house dust mite (HDM) allergen
      natural exposure. Twenty-one children (7-13 yr) with moderate asthma and
      sensitized to HDM were evaluated during a prolonged period of allergen avoidance
      (T0) and after a period of natural allergen exposure (T1). At each time point of
      sputum induction, lung function evaluation, exhaled nitric oxide (eNO)
      measurements were performed. At T1, CCR4 and CCR8 expression on sputum-induced
      cells increased from 28.4% +/- 2.9% and 25.8% +/- 1.9%, to 41.1% +/- 4.2% and
      37.5% +/- 2.0%, respectively (p < 0.05 and p = 0.01). After allergen exposure,
      both sputum eosinophils (from 5.2% +/- 2.0% to 12.1% +/- 4.1%, p < 0.01) and eNO
      (from 15.1 +/- 2.2 ppb to 24.2 +/- 5.8 ppb, p < 0.05) showed significant
      increase. Lung function tests presented significant deterioration of Forced
      Expiratory Flow at 25-75% of Vital Capacity (FEF(25--75)) (p < 0.05) and increase
      of residual volume (p = 0.002). Significant changes in CC chemokine receptor
      expression in sputum-induced cells in asthmatic children in response to HDM
      exposure have been observed leading to consider the relevance of CCR4 and CCR8 in
      allergic asthmatic inflammation.

PMID- 17014624
TI  - Genetic association study between mbl2 and asthma phenotypes in Chinese children.
AB  - Mannose-binding lectin (MBL), a member of the innate immune system, initiates
      complement deposition on microbial surfaces. MBL deficiency is associated with
      severe respiratory infections. Polymorphisms in the MBL gene (mbl2) were
      associated with the susceptibility and severity of autoimmune diseases. This
      study investigated whether mbl2 polymorphisms at positions -550 and -221 and at
      codon-54 are associated with asthma phenotypes in Chinese children. Asthmatics
      aged 5-18 yr and non-allergic controls were eligible, and their plasma total and
      allergen-specific immunoglobulin E (IgE) concentrations were measured by micro
      particle immunoassay and fluorescent enzyme immunoassay. mbl2 polymorphisms were
      genotyped by restriction fragment length polymorphism. Three hundred and
      seventeen asthmatic children and 140 controls were recruited, with their mean
      (s.d.) log-transformed plasma total IgE being 2.61 (0.61) and 1.77 (0.77),
      respectively (p < 0.0001). Polymorphisms at -550 and codon-54 (p < 0.0001 for
      both) but not at -221 (p = 0.534) of mbl2 were significantly associated with
      plasma MBL concentrations. mbl2 genotypes were not associated with asthma, atopy,
      sensitization to individual aeroallergens or spirometric variable. Subjects with
      LYB haplotype had the lowest plasma MBL concentrations (p < 0.0001), but two- and
      three-loci mbl2 haplotypes were also not associated with asthma diagnosis.
      However, patients with LY and LYB haplotypes were less likely to be atopic (p =
      0.006 and 0.031). Subjects with LY and LYA were also less likely to be sensitized
      to cockroach (p = 0.035 and 0.047). The latter three associations became
      insignificant when adjusted for multiple comparisons. Despite the importance of
      MBL in innate immunity, our mbl2 polymorphisms only show weak association with
      asthma and atopy in children.

PMID- 17014625
TI  - ACE gene polymorphism might disclose why some Taiwanese children with allergic
      rhinitis develop asthma symptoms but others do not.
AB  - Although allergic asthma and allergic rhinitis have recently been considered to
      be a single disease, many questions remain unanswered. Why do some atopic
      patients develop asthma symptoms and others develop allergic rhinitis symptoms?
      Which factors play a role in the development of different allergic phenotypes? We
      hypothesized that angiotensin-converting enzyme (ACE) gene polymorphism might
      play a role in the development of asthma phenotypes in children with allergic
      rhinitis. The study sample included 106 children with allergic rhinitis, but no
      asthma, and 105 age- and gender-matched children with allergic rhinitis and
      asthma. Subjects of both groups exhibited the same systemic immunologic changes
      and allergen sensitivities. Controls consisted of 102 healthy children. The ACE
      genotype was determined by polymerase chain reaction. The serum total
      immunoglobulin E (IgE) level, allergen-specific IgE sensitivity, and eosinophil
      count were also measured. The frequencies of the DD genotype were significantly
      higher in the children with both allergic rhinitis and asthma than in the
      children with allergic rhinitis but no asthma [p = 0.018; odds ratio (OR) =
      3.257; (1.222-8.680)]. Results of this study suggest that ACE gene polymorphism
      DD genotype might play a role in the development of the asthma phenotype in
      children with allergic rhinitis.

PMID- 17014626
TI  - Human rhinoviruses in otitis media with effusion.
AB  - Frequent viral upper respiratory tract infections (URTI) are considered to be
      risk factors for otitis media with effusion (OME). Atopy has also been associated
      with both OME and viral infections. The aim of this study was to evaluate the
      presence of viruses in middle ear effusions (MEE) in children 2-7 yr old with
      OME, and to determine risk factors for virus detection in the MEE. MEE samples,
      collected at the time of myringotomy from 37 children with OME were assessed.
      Physical examination, skin prick tests and a standardized questionnaire on OME
      and allergy were also performed. Viral RNA was detected by the use of reverse
      transcription PCR (RT-PCR). Fifteen samples (40.5%) were positive for rhinovirus
      (RV). One enterovirus and no other respiratory viruses were detected. Two out of
      five (40%), 3/7 (43%) and 10/25 (40%) were positive for RV in acute, subacute and
      chronic cases, respectively. Children with frequent episodes of OM, with early
      onset of OM (<2 yr old), and a positive family history of allergy had a
      statistically increased risk of RV detection. The two groups were comparable with
      respect to all other parameters examined. RV is the predominant virus recovered
      by RT-PCR in the middle ear cavity of children with asymptomatic OME, especially
      those with a history of longstanding OME or repeated episodes, or children with a
      family history of allergy. Interactions between allergy and RV infections are
      likely to predispose to middle ear disease.

PMID- 17014627
TI  - Prevalence of allergic rhinitis and nasal smear eosinophilia in 11- to 15 yr-old
      children in Shiraz.
AB  - Allergic rhinitis (AR) is a common condition among schoolchildren. The prevalence
      rate of AR differs among countries and even among regions within the same
      country. The objective of this study was to determine the prevalence of nasal
      symptoms and signs of AR and nasal smear eosinophilia in 11- to 15-yr-old
      children in Shiraz. A total of 4584 children aged 11-15 yr of both sexes were
      surveyed from May 1995 to April 1996, and nasal symptoms and signs of AR
      (sneezing, rhinorrhea, nasal blockage, itching, color change, mucosal swelling,
      nasal wetness, and nasal crease), based on questionnaire and ear, nose and throat
      (ENT) examination were recorded. In addition, smears were taken from nasal
      secretions and stained. The results compared with nasal smears related to 340
      healthy children. 1008 (22%) schoolchildren had nasal symptoms of AR (based on
      the questionnaire), 445 (9.7%) were identified as having nasal symptoms and signs
      of AR (based on the questionnaire and ENT specialist examination), and 226 (5.8%)
      had nasal symptoms and signs of AR associated with nasal eosinophilia (based on
      the questionnaire, ENT specialist examination and positive nasal smear for
      eosinophilia). Nasal eosinophilia was present in 274 (62%) children with nasal
      symptoms and signs of AR. This survey showed that prevalence of nasal symptoms
      and signs of AR was high in schoolchildren in Shiraz. Nasal smear eosinophilia
      had a diagnostic specificity of 96% and sensitivity of 62% and seems to be a
      potentially valuable test for AR.

PMID- 17014628
TI  - Allergic conjunctivitis in children with asthma, rhinitis and eczema in a
      secondary outpatient clinic.
AB  - Little evidence is available on the prevalence of allergic conjunctivitis in
      pediatric populations. The objective of this study was to assess the cumulative
      prevalence of allergic conjunctivitis in children with rhinitis, asthma and
      eczema in a secondary pediatric outpatient clinic. Children aged 5-15 yr referred
      during the period of 2002-2004 in whom allergic conjunctivitis, asthma, allergic
      rhinitis or eczema was diagnosed were included in a retrospective survey. At
      referral patient characteristics, history, symptoms, signs and results of type 1
      allergy tests were entered into an electronic form. Four hundred and fifty-eight
      children with a mean age of 9.4 yr were studied. Of 316, 324 and 149 children
      with rhinitis, asthma or eczema, respectively, 133 (42%), 78 (24%) and 45 (30%)
      had concomitant allergic conjunctivitis. One hundred and thirty-seven (30%) had
      allergic conjunctivitis, of whom 133 (97%) also had allergic rhinitis, 77 (56%)
      asthma and 45 (33%) eczema. One hundred and twenty-five (91%) of the children
      with allergic conjunctivitis had positive allergy tests to one or more allergens,
      sensitization to house dust mites being more frequent in chronic allergic
      conjunctivitis than in acute allergic conjunctivitis (95% vs. 53%; p < 0.01).
      Sensitization to grass was more frequent in children with acute allergic
      conjunctivitis (78% vs. 57%; p = 0.03). In a secondary pediatric outpatient
      clinic allergic conjunctivitis is a frequent co-morbidity to allergic rhinitis
      and to asthma and eczema. Allergic conjunctivitis need to be included as an
      important co-morbidity in future guidelines on asthma, rhinitis and eczema
      management.

PMID- 17014629
TI  - Efficacy of 1.25% and 1% topical cyclosporine in the treatment of severe vernal
      keratoconjunctivitis in childhood.
AB  - Cyclosporine eyedrops 2% have been used for treatment of corticosteroid-resistant
      vernal keratoconjunctivitis (VKC) cases. The purpose of our study was to verify
      the efficacy of 1.25% vs. 1% topical cyclosporine in improving severe form of VKC
      in childhood. Twenty children with severe VKC, were enrolled in a double-blind,
      placebo-controlled study and received cyclosporine 1.25% in one eye for 2 wk.
      Then an open trial was conducted during the next 3 months and 2 wk. Thirty-two
      more patients were recruited the next year into a new open trial and they
      received cyclosporine 1% for 4 months. Ocular subjective symptoms and objective
      signs were scored in all children at entry, 2 wk and 4 months. Skin prick tests
      and conjunctival scraping tests were also performed; serum immunological and
      biochemical markers were assessed. The mean score values for severity of
      subjective symptoms and objective signs were significantly decreased after 2 wk,
      and 4 months, compared with those at entry (p < 0.001), in both groups of
      children who received cyclosporine eyedrops 1.25% and 1%, respectively. Serum
      markers did not differ from the beginning to the end of treatment. Conjunctival
      eosinophils and cyclosporine serum levels were not detectable at the end of
      therapy, nor were endothelial corneal cells damaged. Our findings suggest that 1%
      cyclosporine concentration might be the minimal effective treatment regimen to
      control symptoms and local inflammation in severe forms of VKC.

PMID- 17014630
TI  - Is affluence a risk factor for bronchial asthma and type 1 diabetes?
AB  - In the last decades, an increase in bronchial asthma and type 1 diabetes
      occurrence has been observed in affluent countries, and a positive association
      between the two disorders has been demonstrated at the population level. This
      association could be explained by common risk factors predisposing to both
      disorders. Altered environmental and lifestyle conditions, possibly related to
      socio-economic status, might account for the rising trend of the two disorders.
      To test this hypothesis, we calculated the correlation between the occurrence of
      type 1 diabetes and asthma, the gross national product (GNP) and the infant
      mortality rate, in several European and extra-European countries. GNP was
      positively correlated with the incidence of type 1 diabetes and with symptoms of
      asthma in European (r(sp): 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively)
      and extra-European countries (r(sp): 0.44 and 0.46; p = 0.04 for both diseases).
      Infant mortality rate was inversely correlated with GNP and with the occurrences
      of the two diseases in Europe (r(sp): -0.66, p < 0.0001 for type 1 diabetes;
      r(sp):- 0.51, p = 0.01 for asthma). In extra-European countries, a significant
      relationship was found between infant mortality and asthma (r(sp): -0.46; p =
      0.03); a trend towards a negative correlation between infant mortality and type 1
      diabetes was also found, although no statistical significance was reached (r(sp):
      -0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are
      positively associated with the GNP at the population level. Similarly, countries
      with low infant mortality rates tend to have a higher incidence of these immune
      mediated diseases. Although GNP reflects many societal and lifestyle differences,
      it is notable that a high socio-economic status implies a reduced or delayed
      exposure to infectious agents. The reduced pressure of infectious agents on the
      immune system throughout life might contribute to increase the susceptibility to
      bronchial asthma and type 1 diabetes.

PMID- 17014631
TI  - Dietary insulin as an immunogen and tolerogen.
AB  - We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula
      induces an insulin-specific immune response in infants. Here we studied the role
      of human insulin (HI) in breast milk as a modulator of the immune response to
      insulin. In a group of 128 children participating in the TRIGR pilot study,
      maternal breast milk samples were collected 3-7 days and/or 3 months after
      delivery. After exclusive breast-feeding, the children received either CM formula
      or casein hydrolysate during the first 6-8 months of life. Insulin concentration
      in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were
      measured by EIA. The levels of insulin in breast milk samples were higher in
      mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p
      < 0.001). The concentration of insulin in breast milk correlated inversely with
      the plasma levels of IgG antibodies to BI at 6 months of age in children who
      received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all
      children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in
      the mothers of nine children who developed beta-cell autoimmunity when compared
      with autoantibody-negative children (p = 0.030); this holds true also when only
      children of diabetic mothers were included (p = 0.045). BI in CM induces higher
      levels of IgG to insulin in infants than does HI in breast-fed children. Instead,
      HI in breast milk seems to be tolerogenic and may downregulate the IgG response
      to dietary BI. However, our results in infants who developed beta-cell
      autoimmunity suggest that in this subgroup of children breast milk insulin does
      not promote tolerance.

PMID- 17014634
TI  - Tributes to Nancy B. Esterly, M.D., pediatric dermatologist, mentor, and editor
      extraordinaire.

PMID- 17014632
TI  - Isolated IgG3 deficiency in children: to treat or not to treat? Case presentation
      and review of the literature.
AB  - Immunoglobulin G3 (IgG3) subclass deficiency has received rather little attention
      thus far. In this report, the clinical and immunologic characteristics of six
      children with isolated IgG3 deficiency are discussed. The currently available
      literature on IgG3 deficiency is reviewed with specific emphasis on the
      peculiarities of the IgG3 subclass, the clinical relevance of IgG3 deficiency as
      well as the therapeutic options.

PMID- 17014635
TI  - A single-blinded, randomized, controlled clinical trial evaluating the effect of
      face washing on acne vulgaris.
AB  - Despite the common recommendation to wash the face twice daily with a mild
      cleanser, there is little published evidence to support the practice. Indeed,
      while the general public believes that cleaner skin will result in fewer
      blemishes, dermatologists often warn that overwashing and scrubbing can
      exacerbate the condition. To clarify the effect of frequency of face washing on
      acne vulgaris, we designed a single-blinded, randomized, controlled clinical
      trial to be conducted on males with mild to moderate acne vulgaris. Subjects
      washed their faces twice daily for 2 weeks with a standard mild cleanser before
      being randomized to one of three study arms, in which face washing was to be done
      once, twice, or four times a day for 6 weeks. At the end of the study no
      statistically significant differences were noted between groups. However,
      significant improvements in both open comedones and total noninflammatory lesions
      were observed in the group washing twice a day. Worsening of acne condition was
      observed in the study group washing once a day, with significant increases in
      erythema, papules, and total inflammatory lesions. We concluded that slight
      support exists, both in terms of efficacy and convenience, for the recommendation
      to wash the face twice daily with a mild cleanser. However, excessive face
      washing may not be as culpable as previously thought.

PMID- 17014636
TI  - Pediatric atopic eczema: the impact of an educational intervention.
AB  - Patient education has been regarded as having a key role in the self-management
      of atopic eczema. However, the relationship between the educational interventions
      and clinical outcomes including severity of eczema, quality of life, and family
      impact has not been rigorously examined. The purpose of this longitudinal
      randomized controlled study was to evaluate the impact of an intensive education
      program with a focus on dermatology and immunology designed for parents and
      children diagnosed with atopic eczema. The intention of this study was not to
      change treatment regimes prescribed by the patient's physician. The Scoring
      Atopic Dermatitis rating system was used for assessment of disease impact, and
      the impact on quality of life was quantified by using the Children's Dermatology
      Life Quality Index, Infants' Dermatology Quality of Life Index, and Dermatitis
      Family Impact. A total of 61 pediatric patients (0-16 years) diagnosed with
      atopic eczema from the metropolitan area of Adelaide were randomized to either
      the control or intervention group. Results of the study showed that the
      intervention group had a significant improvement in the scoring atopic dermatitis
      measure when compared to the control group at week 4 and week 12. Quality of life
      measures did not significantly improve with decreased severity of eczema except
      in the group of children aged 5-16 years which, despite small numbers, showed a
      significant improvement in quality of life scores. These findings suggest that
      education provides an important role in decreasing the severity of eczema.

PMID- 17014637
TI  - The prognostic value of nailfold capillary changes for the development of
      connective tissue disease in children and adolescents with primary raynaud
      phenomenon: a follow-up study of 250 patients.
AB  - To assess the prognostic value of capillaroscopy findings for the development of
      connective tissue disease in children and adolescents with Raynaud phenomenon, we
      followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first
      capillaroscopy was performed. Every 6 months they were screened for signs and
      symptoms of connective tissue disease. Analysis was performed on capillary
      changes registered 6 months before the development of connective tissue disease.
      Capillary changes were classified into three types: normal, nonspecific, and
      sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had
      primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated
      connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis
      of a specific connective tissue disease. Systemic lupus erythematosus was found
      in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them
      with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in
      13 (5.2%). The mean time for the evolution of Raynaud phenomenon into
      undifferentiated connective tissue disease or a form of the disease was 2 years.
      Most of the subjects with primary Raynaud phenomenon (173/191, 91%),
      undifferentiated connective tissue disease (22/27, 81%), juvenile onset
      rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus
      erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary
      changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9
      (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated
      connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of
      all the subjects, only 10 (4%) showed sclerodermatous disease type capillary
      changes 6 months before the expression of a particular disease: eight (62%) of
      these developed scleroderma spectrum disorders, one expressed systemic lupus
      erythematosus, and one had undifferentiated connective tissue disease. We
      concluded that there were no specific capillary changes predictive for future
      development of systemic lupus erythematosus, juvenile onset rheumatoid
      arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in
      children and adolescents with Raynaud phenomenon. Most of our study subjects with
      Raynaud phenomenon who developed these diseases had normal capillary findings or
      nonspecific changes. Children and adolescents who developed scleroderma spectrum
      disorders showed a sclerodermatous type of capillary changes 6 months before the
      expression of the disease, indicating that this type of capillary changes in
      children and adolescents with Raynaud phenomenon highly correlated with further
      development of scleroderma spectrum disorders.

PMID- 17014638
TI  - Linear IgA bullous disease of childhood: an experience from Kuwait.
AB  - Linear IgA bullous disease of childhood is a rare autoimmune blistering disease.
      We report eight patients with this disease seen in our autoimmune bullous
      diseases clinic over a span of 12 years. They constituted 89% of the total number
      of those with linear IgA bullous disease of childhood seen during this period,
      with an age-adjusted minimum estimated incidence of 2.3 cases/million
      population/year. Males outnumbered females by a 1.7:1 ratio. The age at onset
      ranged between 10.5 months and 13 years, with a mean of 6.8 +/- 4.17 years. The
      majority of patients (62.5%) had moderately severe disease. Fifty percent of
      patients were observed to have an association with either an autoimmune disease
      (Crohn disease and post-streptococcal glomerulonephritis in one each) or an
      infection (beta-hemolytic streptococcal and hepatitis A virus infection in one
      each). The treatment of choice was dapsone alone or in combination with systemic
      steroids. Seventy-one percent of patients achieved complete remission by the end
      of 2 years. The study highlights the significance of systematic
      clinicoepidemiologic surveys from different regions.

PMID- 17014639
TI  - Traumatic keratoacanthoma arising in a 15-year-old boy following a motor vehicle
      accident.
AB  - Keratoacanthomas appear most commonly in sun-damaged skin in middle-aged and
      elderly people. We present a 15-year-old boy who developed a rapidly growing
      nodule within a hypertrophic scar that was the result of trauma suffered in a
      roll-over motor vehicle accident 8 months prior to presentation. Histologic
      analysis of a biopsy specimen of the nodule confirmed the presence of squamous
      cell carcinoma, keratoacanthoma type. The development of keratoacanthoma has been
      associated with sun exposure, chemical carcinogens, radiation therapy, genetic
      factors, and various forms of antecedent trauma, including surgery or grafting,
      thermal burns, laser resurfacing, and vaccination. This report describes the
      youngest patient with traumatically-induced keratoacanthoma, and is the first
      instance of this entity arising in a friction burn.

PMID- 17014640
TI  - Celiac disease presenting with chilblains in an adolescent girl.
AB  - Chilblains, or pernio, are cutaneous lesions that may accompany systemic
      illnesses including states of malnutrition and autoimmune diseases. We report an
      adolescent girl in whom chilblains were the chief presenting sign of celiac
      disease. A gluten-free diet led to weight gain and resolution of the chilblains.
      We speculate that in this patient, weight loss due to celiac disease contributed
      to the development of chilblains.

PMID- 17014641
TI  - Video game induced knuckle pad.
AB  - Controversy and concern surround the video game playing fascination of children.
      Scientific reports have explored the negative effects of video games on youth,
      with a growing number recognizing the actual physical implications of this
      activity. We offer another reason to discourage children's focus on video games:
      knuckle pads. A 13-year-old black boy presented with an asymptomatic, slightly
      hyperpigmented plaque over his right second distal interphalangeal joint. A punch
      biopsy specimen confirmed knuckle pad as the diagnosis, and a traumatic etiology
      from video game playing was suspected. Knuckle pads can be painful, cosmetically
      unappealing, and refractory to treatment. They can now be recognized as yet
      another potential adverse consequence of chronic video game playing.

PMID- 17014642
TI  - Exuberant juvenile hyaline fibromatosis in two patients.
AB  - Juvenile hyaline fibromatosis and infantile systemic hyalinosis are rare
      autosomal recessive disorders of infancy and early childhood that are
      histologically characterized by deposition of hyaline material. The main clinical
      features are papulo-nodular skin lesions, gingival hypertrophy, joint
      contractures, and bone abnormalities. However, infantile systemic hyalinosis has
      a more severe clinical presentation, including visceral involvement and premature
      death. Very recently, genetic studies identified mutations in the same gene in
      patients with both conditions, strongly suggesting that they belong to the same
      disease spectrum. We report two new nonrelated patients who met the criteria for
      the diagnosis of juvenile hyaline fibromatosis/infantile systemic hyalinosis.
      Clinical, histopathologic, immunohistochemical, and ultrastructural findings are
      presented, as well as an extensive review of the literature. Recent information
      regarding pathogenesis and treatment is discussed.

PMID- 17014643
TI  - Porokeratotic eccrine ostial and dermal duct nevus.
AB  - Porokeratotic eccrine ostial and dermal duct nevus is a rare disorder
      characterized by distinctive histopathology. We describe a 6-year-old boy who had
      the typical palmar involvement and small discrete areas involving the midline of
      his back.

PMID- 17014644
TI  - Geroderma osteodysplastica. Report of a new family.
AB  - We report a family in which geroderma osteodysplastica affected two male
      siblings. They showed the characteristic features associated with this syndrome:
      a prematurely aged face with wrinkly, lax skin, more prominent on the acral
      regions, associated with joint laxity, osteoporosis, and skeletal abnormalities.
      The main histologic abnormalities were fragmented elastic fibers that were
      diminished in number. Although collagen fibers showed changes in their
      orientation, they were normal in structure and number. We consider the
      differential diagnosis with other syndromes associated with cutis laxa using
      clinical, radiologic, and histopathologic criteria.

PMID- 17014645
TI  - Fontana-positive grains in mycetoma caused by Microsporum canis.
AB  - We describe mycetoma caused by Microsporum canis occurring in a 9-year-old
      African-American girl. Pathologic evaluation showed a granulomatous dermatitis
      with numerous large fungal grains containing septate hyphae that were Fontana
      Masson positive. Two cultures of pure grains grew M. canis. Mycetoma due to
      dermatophytes is very uncommon. The few instances reported have been
      pseudomycetoma (grains in the absence of sinus tracts). Our patient developed
      sinus tracts (true mycetoma). No prior reports were found of M. canis staining
      Fontana positive. Differentiation of dermatophyte-induced mycetoma from kerion is
      important because mycetomas require a combined approach including surgical
      debridement in addition to oral antifungal therapy.

PMID- 17014646
TI  - Hypopituitarism in PHACES Association.
AB  - The association consisting of posterior fossal malformations, cervicofacial,
      hemangiomas, arterial anomalies, cardiac defects, eye anomalies, and sternal
      clefting, or supraumbilical raphe, refers to the occurrence of congenital
      structural and vascular anomalies in the presence of a facial hemangioma. We
      report a patient with this association, growth retardation, and developmental
      delay who was found to have a partially empty sella turcica, central
      hypothyroidism, and growth hormone deficiency. Endocrinologic evaluation should
      be considered in any infant with this association.

PMID- 17014647
TI  - Mycobacterium haemophilum in an immunosuppressed child.
AB  - Mycobacterium haemophilum is an emerging cutaneous and systemic pathogen in
      immunosuppressed adults. Reports in the pediatric literature prior to 2004,
      limited to immunocompetent children with lymphadenitis, offer a different
      clinical presentation from that of the immunosuppressed adult. We report an
      instance of this atypical mycobacterial infection occurring in an
      immunosuppressed boy with clinical findings similar to those described in
      immunosuppressed adults.

PMID- 17014648
TI  - Deep morphea after vaccination in two young children.
AB  - A number of dermatoses have been reported to appear in close temporal or spatial
      relationship to the intramuscular injection of vaccines. We describe two young
      children who had morphea consistent with the deep morphea type (morphea profunda)
      that appeared at the site of a previous vaccination. Trauma has been implicated
      as an important trigger of morphea, both in children and in adults. Furthermore,
      vaccines might induce an immune response, which could lead to morphea in
      predisposed individuals.

PMID- 17014649
TI  - Inflammatory peeling skin syndrome studied with electron microscopy.
AB  - Peeling skin syndrome is a rare autosomal recessive dermatosis characterized by
      lifelong continual skin shedding with underlying erythema. We present a 10-year
      old boy with this disease. Easy peeling of the skin associated with keratotic
      areas was observed. Microscopic findings included psoriasiformis dermatitis.
      Cleavage was observed between corneocytes as well as between granular-corneum
      cells and within the granular cell layer. Electron microscopic findings included
      intra- and intercellular cleavage of corneocytes and intracellular separation of
      granular cells. The molecular mechanisms of peeling skin syndrome are discussed.

PMID- 17014650
TI  - Hypopigmented mycosis fungoides associated with atopy in two children.
AB  - Mycosis fungoides is very rare in children. Hypopigmented lesions of this disease
      are usually observed in dark-skinned individuals and often show a T supressor
      CD8(+) phenotype. Two Caucasian children with predominantly hypopigmented lesions
      of mycosis fungoides are presented here. Atopy was a concomitant feature in both.

PMID- 17014651
TI  - Nonpigmenting confluent and reticulated papillomatosis.
AB  - We report three teenaged Caucasian patients with confluent and reticulated
      papillomatosis whose presentation was atypical due to the absence of
      hyperpigmentation and presence of a fine white scale.

PMID- 17014652
TI  - Lichen sclerosus of the lip.
AB  - Lichen sclerosus is a chronic inflammatory mucocutaneous disorder predominately
      affecting prepubertal girls and postmenopausal women. Isolated lichen sclerosus
      affecting the oral mucosa is exceedingly rare. Only 13 patients with biopsy
      proved isolated oral disease have been reported in the literature. We report a 10
      year-old Caucasian girl with a well-demarcated 1.5 cm x 1.2 cm atrophic white
      plaque with a violaceous border and focal telangiectases on the right inferior
      vermillion lip, extending on to the labial mucosa. No other cutaneous surfaces,
      including genitalia, were involved. Incisional biopsy of the plaque on the lip
      revealed a patchy lichenoid infiltrate of lymphocytes associated with sclerosis
      of the papillary dermis and a thinned epidermis consistent with a diagnosis of
      lichen sclerosus. Treatment with a short course of high potency topical
      corticosteroids likely prevented the progression of this lesion.

PMID- 17014653
TI  - Dactinomycin-induced, severe lichenoid eruption in a child.
AB  - There is little information in the medical literature about skin rashes
      associated with dactinomycin in the absence of radiotherapy. We report a 12-month
      old male child who developed a severe cutaneous reaction that consisted of a
      widespread pruritic papular eruption associated with fever and a poor general
      state after dactinomycin administration. Skin biopsy specimen findings confirmed
      the diagnosis of lichenoid eruption. The rash improved with topical steroid
      treatment and completely resolved within 1 month with persistence of a residual
      mild hyperpigmentation. Dactinomycin administration was discontinued for the
      remaining cycles of chemotherapy.

PMID- 17014654
TI  - Successful treatment of pediatric psoriasis with Indigo naturalis composite
      ointment.
AB  - The treatment of psoriasis in children is still an intractable problem and
      demands a long-term therapy with prolonged efficacy that is free from serious
      adverse events. Many modes of therapy are currently in use but the disease is
      often resistant to treatment owing to the unacceptable toxicity that leads to
      poor compliance. Therefore, to develop an alternative treatment is indispensable.
      Traditional Chinese medicine has been documented for over 1000 years to provide
      various effective treatments for inflammatory skin diseases. Herein, we report an
      8-year-old boy with recalcitrant pediatric psoriasis who, after multiple
      treatment failures with conventional antipsoriatic medications, showed remarkable
      clinical improvement with 8 weeks of topical treatment with Indigo naturalis
      composite ointment. Remission has lasted for over 2 years until now. Our
      patient's response suggests that topical Indigo naturalis composite ointment may
      provide a safe and effective alternative treatment for pediatric psoriasis.

PMID- 17014655
TI  - What syndrome is this? Treacher Collins-Franceschetti syndrome.

PMID- 17014656
TI  - Painless mobile mass on the dorsum of the foot of a 3-month-old girl.

PMID- 17014657
TI  - Eccrine angiomatous hamartoma associated with spontaneous regression.

PMID- 17014658
TI  - Candida albicans allergenic extract induces toll-like receptor expression and
      increases interferon-alpha production.

PMID- 17014659
TI  - Acute generalized facial erythema and swelling associated with oral isotretinoin
      in a child.

PMID- 17014660
TI  - Localized hair breakage caused by ants.

PMID- 17014661
TI  - How should one study wound healing?

PMID- 17014662
TI  - Transforming growth factor-beta3 affects plasminogen activator inhibitor-1
      expression in fetal mice and modulates fibroblast-mediated collagen gel
      contraction.
AB  - For over two decades, the precise role of transforming growth factor-beta (TGF
      beta) isoforms in scarless healing of mammalian fetal skin wounds has generated
      much interest. Although their exact role remains to be established, it has been
      suggested that high TGF-beta3 activity may correlate with a scarless phenotype.
      Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF
      beta downstream molecule and marker of fibrosis, is also developmentally
      regulated during fetal skin development. In this study, the relationship between
      TGF-beta3 and PAI-1 was investigated using embryonic day 14.5 TGF-beta3 knockout
      (ko) mice. The results showed increased PAI-1 expression in the epidermis and
      dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased
      PAI-1 expression and activity was seen in embryo extracts and conditioned media
      of ko dermal fibroblasts. When TGF-beta3 knockout fibroblasts were placed into
      three-dimensional collagen matrices, they were found to have decreased collagen
      gel contraction, suggesting altered cell-matrix interaction. These findings
      provide a further avenue for the interactive role of TGF-beta3 and PAI-1 during
      fetal scarless repair.

PMID- 17014663
TI  - A randomized, double-blind, placebo-controlled multicenter trial evaluating
      topical zinc oxide for acute open wounds following pilonidal disease excision.
AB  - The purpose of this randomized, double-blind, placebo-controlled multicenter
      trial was to compare topical zinc oxide with placebo mesh on secondary healing
      pilonidal wounds. Sixty-four (53 men) consecutive patients, aged 17-60 years,
      were centrally randomized to either treatment with 3% zinc oxide (n = 33) or
      placebo (n = 31) by concealed allocation. Patients were followed with strict
      recording of beneficial and harmful effects including masked assessment of time
      to complete wound closure. Analysis was carried out on an intention-to-treat
      basis. Median healing times were 54 days (interquartile range 42-71 days) for the
      zinc and 62 days (55-82 days) for the placebo group (p = 0.32). Topical zinc
      oxide increased (p < 0.001) wound fluid zinc levels to 1,540 (1,035-2,265) microM
      and decreased (p < 0.05) the occurrence of Staphylococcus aureus in wounds. Fewer
      zinc oxide (n = 3) than placebo-treated patients (n = 12) were prescribed
      postoperative antibiotics (p = 0.005). Serum-zinc levels increased (p < 0.001)
      postoperatively in both groups but did not differ significantly between the two
      groups on day 7. Zinc oxide was not associated with increased pain by the visual
      analog scale, cellular abnormalities by histopathological examination of wound
      biopsies, or other harmful effects. Larger clinical trials will be required to
      show definitive effects of topical zinc oxide on wound healing and infection.

PMID- 17014664
TI  - Longer-term changes in quality of life in chronic leg ulceration.
AB  - Studies that have examined patients' health-related quality of life have
      consistently shown improvements following intensive and effective treatments over
      relatively short follow-ups. However, little is known of the longer-term effects
      of treatment on patients. As part of a study in southwest London, United Kingdom,
      all patients having a current leg ulcer were examined (n = 113) and those who
      were able completed the Nottingham Health Profile (n = 95) and were then followed
      up at 24 and 48 weeks. The patients had a mean age of 76 +/- 13 (SD) years, with
      60 (63.2%) being women. Before the study, the ulcer had been present for a median
      of 8 months (range 0.5-144), and a median area of ulceration of 4.0 cm2 (range
      0.5-171.5 cm2). After 24 weeks, there was a significant improvement in pain (mean
      difference [d] = 9.6, p = 0.002), which was true for both the 41 patients with
      ulcers present (d=10.07, p = 0.013) and the 43 patients whose ulcers had healed
      (d = 11.46, p = 0.047). However, after 48 weeks, these improvements had been
      reduced in both groups (healed ulceration d = 5.76, unhealed patients d = 6.41).
      Energy, which had improved after 24 weeks in the patients whose ulcers, had
      healed (d = 11.46), deteriorated in both patient groups after 48 weeks (healed = 
      5.67, unhealed = -13.43). Mobility status was maintained with healed ulceration
      (d = 1.05) but deteriorated with unhealed ulceration (d = -13.19). The positive
      effects of treatment on health-related quality of life may not be sustained over
      time. This may be a consequence of the general deterioration in the health status
      of these elderly patients as they age.

PMID- 17014665
TI  - Long-term invasive measurement of subcutaneous oxygen partial pressure above the
      sacrum on lying healthy volunteers.
AB  - Pressure ulcers are frequently seen dermal lesions, but little is known about
      their pathophysiology. It is generally assumed that prolonged tissue pressure
      impairs blood circulation thus causing ischemic damage to tissue. Therefore,
      subcutaneous oxygen partial pressure was measured to confirm this hypothesis. In
      the past, various authors have conducted tests on healthy subjects to determine
      oxygen partial pressure transcutaneously during periods not exceeding 20 minutes.
      All found a decrease at susceptible sites, e.g., the sacrum. The present study
      was the first one to measure oxygen partial pressure subcutaneously above the
      sacrums of four test subjects during a period of 5 hours. In all cases, the
      values first decreased to a minimum of 37% of baseline before they returned to
      the initial values. This observation is in contradiction to former studies, which
      start from the assumption of critical ischemia due to interface pressure,
      measured on healthy volunteers too.

PMID- 17014666
TI  - Diagnostic validity of three swab techniques for identifying chronic wound
      infection.
AB  - This study examined the diagnostic validity of three different swab techniques in
      identifying chronic wound infection. Concurrent swab specimens of chronic wounds
      were obtained using wound exudate, the Z-technique, and the Levine technique,
      along with a specimen of viable wound tissue. Swab and tissue specimens were
      cultured using quantitative and qualitative laboratory procedures. Infected
      wounds were defined as those containing 1 x 10(6) or more organisms per gram of
      tissue. Accuracy was determined by associating the quantitative cultures of swab
      specimens with the cultures from tissue specimens using receiver operating
      characteristic curves. Of the 83 study wounds, 30 (36%) were infected. Accuracy
      was the highest for swab specimens obtained using Levine's technique at 0.80.
      Based on Levine's technique, a critical threshold of 37,000 organisms per swab
      provided a sensitivity of 90% and a specificity of 57%. The mean concordance
      between swab specimens obtained using Levine's technique and tissue specimens was
      78%. The findings suggest that swab specimens collected using Levine's technique
      provide a reasonably accurate measure of wound bioburden, given that they are
      more widely applicable than tissue cultures. The diagnostic validity of Levine's
      technique needs further study using an alternative reference standard, such as
      the development of infection-related complications.

PMID- 17014667
TI  - Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial
      cells in the margin of chronic diabetic foot ulcers.
AB  - Keratinocytes and dermal endothelial cells, excluding leukocytes that infiltrate
      wounds, are the main source of soluble factors regulating healing of skin ulcers.
      We used immunohistochemistry to analyze the expression of various chemotactic and
      growth factors and their receptors in the margin of diabetic foot ulcers and in
      normal nondiabetic foot skin. Our study found significantly elevated expression
      of transforming growth factor-beta1 (TGF-beta1) and type I TGF-beta receptors
      (TGFbetaR1), granulocyte macrophage colony-stimulating factor (GM-CSF), and
      epidermal growth factor (EGF) in keratinocytes in the ulcer margin (p < 0.05).
      Significantly increased expression of monocyte chemotactic protein-1, GM-CSF,
      CXCR1, and TGFbetaRI and decreased expression of interleukin (IL)-10, IL-15, and
      TGF-beta1 were observed in ulcer dermal endothelial cells (p < 0.05). There was a
      lack of up-regulation of IL-8, CCR2A, IL-10 receptor, GM-CSF receptor, platelet
      derived growth factors and their receptors, vascular endothelial growth factor
      and its type II receptor, EGF receptor, insulin-like growth factor-1, and nitric
      oxide synthase-2 in both KCs and endothelial cells in the ulcer. Finally, there
      was a lack of up-regulation of IL-10 and IL-15 in keratinocytes and of EGF, basic
      fibroblast growth factor, and nitric oxide synthase-3 in endothelial cells in the
      ulcer margins. The enhanced expression of some factors responsible for KC
      behavior could suggest an unimpaired capacity of keratinocytes to reepithelialize
      the margin of diabetic foot ulcers. However, lack of up-regulation of some
      angiogenic and leukocyte chemotactic factors, associated with the reduced influx
      of immune cells, may account for a poor formation of granulation tissue and
      chronicity of ulcer epithelialization.

PMID- 17014668
TI  - Profiles of inflammatory cytokines following colorectal surgery: relationship
      with wound healing and outcome.
AB  - Inflammation is an essential component of normal wound healing. This study has
      correlated systemic (plasma) and local (wound fluid) concentrations of
      inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha [TNF
      alpha], and IL-1beta) with wound healing and surgical outcome following elective
      colorectal surgery. Paired plasma and wound fluid samples were collected (n = 44)
      postoperatively (days 1, 3, 5, 7) and analyzed by enzyme-linked immunosorbent
      assay (pg/mL). Cytokine levels were significantly greater in drain fluid than
      plasma on each postoperative day (POD); e.g., POD 1 : IL-6; drain fluid, median,
      77,050 pg/mL (range 9,928-456,408); plasma, 241 pg/mL (22-1,333). Daily profiles
      of IL-6 and TNF-alpha were similar in drain fluid and plasma; IL-6 levels peaked
      on POD 1 decreasing to POD 7, and TNF-alpha levels increased from PODs 1 to 7.
      However, IL-1beta in plasma peaked on POD 1 and plateaued, whereas drain fluid
      showed two peaks (PODs 1 and 7). Only plasma levels of cytokines correlated to
      clinical parameters; IL-6 levels significantly correlated with postoperative
      complications; e.g., POD 5, complications 92(1-597) and no complications, 14(2
      217). IL-6 also correlated with tumor pathology (Dukes stage, tumor depth,
      vascular invasion), and TNF-alpha levels correlated with the estimated blood loss
      during surgery. We conclude that local wound levels of cytokines correlated with
      the stage of wound healing, whereas systemic levels correlated with postoperative
      complications and tumor pathology.

PMID- 17014669
TI  - Freeze-dried platelet-rich plasma shows beneficial healing properties in chronic
      wounds.
AB  - Fresh platelet concentrates are used in many centers to treat recalcitrant
      wounds. To extend the therapeutic shelf-life of platelets, we analyzed the wound
      healing effects of fresh-frozen and freeze-dried (FD) platelet-rich plasma (PRP)
      using a diabetic mouse model. Db/db mice with 1.0 cm2 dorsal excisional wounds (n
      = 15/group) were treated with a single application of FD PRP (1.2 x 10(6)
      platelets/microL) with or without a stabilization solution, and compared with
      wounds treated with fresh-frozen, sonicated PRP, and untreated wounds.
      Granulation tissue area, thickness, and wound size were analyzed 9 days
      posttreatment. Immunostained sections were quantified for vascularity and
      proliferation using antiplatelet endothelial cell adhesion molecule I and
      antiproliferating cell nuclear antigen antibodies. The results showed that all
      PRP preparations increased granulation tissue formation as assessed by surface
      coverage, thickness, and angiogenic response, when compared with untreated
      wounds. In addition, wounds treated with FD PRP, and biochemically stabilized FD
      PRP, exhibited higher proliferative levels. The possibility to deliver growth
      factors using platelets, and the potential to extend the shelf-life of platelet
      concentrates makes freeze-drying methods particularly suitable for enhanced wound
      care.

PMID- 17014670
TI  - Antibacterial properties of EMLA and lidocaine in wound tissue biopsies for
      culturing.
AB  - If a tissue biopsy from a chronic wound is sampled for culture, the antibacterial
      properties of local anesthetics may pose a problem in producing false-negative
      results. The purpose of this study was to investigate the effects of EMLA
      (AstraZeneca) and lidocaine on common wound pathogenic bacteria. An in vitro
      study of a total of 25 clinical isolates and ATCC reference strains of
      Staphylococcus aureus (including methicillin-resistant S. aureus), Escherichia
      coli, Pseudomonas aeruginosa, and Streptococcus pyogenes was conducted. The
      isolates were exposed to the local anesthetic drugs (and some of their contents
      separately) at 35 degrees C over a 24-hour period and time-kill curves were
      recorded. No culture media were used and saline was used for controls. EMLA was
      found to have a rapid acting and powerful antibacterial effect and should not be
      used before culturing tissue samples. Lidocaine 1% was found not to inhibit the
      bacterial strains when exposure time was held below 2 hours. We conclude that
      culturing tissue from a wound biopsy is safe within 2 hours when a pure,
      preservative-free lidocaine 1% solution is used.

PMID- 17014671
TI  - Influence of vascularized transplant bed on fat grafting.
AB  - Recent advances in regenerative medicine have opened up the option of materials
      used for transplantation. However, only a few studies have examined the take of
      transplanted tissues. We attempted to establish a functional bed for transplanted
      tissues using growth factors. A cylinder-type silicone substrate (spacer) was
      coated with a photoreactive gelatin containing basic fibroblast growth factor.
      This spacer was transplanted into the dorsal subdermal layer in a rabbit. After 2
      and 4 weeks, the capsule formed around the spacer was histologically assessed for
      use as a transplant bed. In addition, after 2-4 weeks of spacer grafting,
      autologous fat was transplanted into the capsule. After 4 more weeks, the grafted
      fat was assessed immunohistochemically to evaluate the capsule as a functional
      bed for transplantation. In the groups pretreated with growth factors,
      proliferation of blood vessels was observed in the capsules. After fat grafting,
      a pattern of overall necrosis was observed in controls. However, good
      proliferation of blood vessels and favorable fat take were observed in the groups
      pretreated with growth factors. Necrosis, however, was found at the center of the
      grafted fat. We conclude that a vascularized transplant bed was useful for
      promoting take of the grafted fat.

PMID- 17014672
TI  - SBD.4 stimulates regenerative processes in vitro, and wound healing in
      genetically diabetic mice and in human skin/severe-combined immunodeficiency
      mouse chimera.
AB  - In search of novel angiostimulators, we performed a high-throughput screening of
      medicinal plants beneficial for blood circulation. From the panel of positive
      hits, Angelica sinensis was selected for further investigation. Purified down to
      a low-molecular-weight fraction and characterized by high-performance liquid
      chromatography-mass spectrometry, the material, named SBD.4A, revealed a
      particularly strong wound healing activity in the diabetic mouse wound-healing
      model, and in the human/severe combined immunodeficiency mouse chimera wound
      healing model. In both models, SBD.4A compared favorably with the Food and Drug
      Administration-approved wound-healing drug becaplermin, suggesting that this
      botanical product could be a valuable treatment for difficult-to-heal wounds.
      Further high-performance liquid chromatography fractionation of SBD.4A yielded a
      hydrophilic fraction, which strongly stimulated endothelial cell proliferation,
      tridimensional endothelial cell network formation, as well as the proliferation
      of human dermal fibroblasts and type I collagen secretion. Because angiogenesis
      and fibroblast proliferation are essential for wound healing, we propose that
      this liquid chromatography-mass spectrometry-defined hydrophilic fraction is at
      least partially responsible for the wound-healing activity of SBD.4A.

PMID- 17014673
TI  - Administration of prednisolone phosphate-liposomes reduces wound contraction in a
      rat partial-thickness wound model.
AB  - Macrophages play an important role in the inflammatory phase of wound healing and
      their activity regulates fibroblasts and keratinocytes. Modulation of macrophage
      function may result in improvement of the wound healing process. Prednisolone
      phosphate (PLP) encapsulated into liposomes was administered to partial-thickness
      wounds in rats. A single dose of 75 microg/kg, applied directly after wounding,
      resulted in up to a 30% reduction of wound contraction at 28 days after wounding.
      This effect could not be achieved in the group that was administered free PLP or
      liposomes containing phosphate-buffered saline to the wound. The number of
      myofibroblasts was up to 50% lower in wounds treated with the liposomal PLP at 4
      days after wounding. The number of macrophages present in the wounds was not
      statistically different between groups. Most probably, the production of
      cytokines and growth factors by macrophages is altered after phagocytosing the
      liposomes, resulting in reduced wound contraction.

PMID- 17014675
TI  - Delivery of plasmid DNA expression vector for keratinocyte growth factor-1 using
      electroporation to improve cutaneous wound healing in a septic rat model.
AB  - We have previously shown that wound healing was improved in a diabetic mouse
      model of impaired wound healing following transfection with keratinocyte growth
      factor-1 (KGF-1) cDNA. We now extend these findings to the characterization of
      the effects of DNA plasmid vectors delivered to rats using electroporation (EP)
      in vivo in a sepsis-based model of impaired wound healing. To assess plasmid
      transfection and wound healing, gWIZ luciferase and PCDNA3.1/KGF-1 expression
      vectors were used, respectively. Cutaneous wounds were produced using an 8 mm
      punch biopsy in Sprague-Dawley rats in which healing was impaired by cecal
      ligation-induced sepsis. We used National Institutes of Health image analysis
      software and histologic assessment to analyze wound closure and found that EP
      increased expression of gWIZ luciferase vector up to 53-fold compared with
      transfection without EP (p < 0.001). EP-assisted plasmid transfection was found
      to be localized to skin. Septic rats had a 4.7 times larger average wound area on
      day 9 compared with control (p < 0.001). Rats that underwent PCDNA3.1/KGF-1
      transfection with EP had 60% smaller wounds on day 12 compared with vector
      without EP (p < 0.009). Quality of healing with KGF-1 vector plus EP scored 3.0
      +/- 0.3 and was significantly better than that of 1.8 +/- 0.3 for treatment with
      vector alone (p < 0.05). We conclude that both the rate and quality of healing
      were improved with DNA plasmid expression vector for growth factor delivered with
      EP to septic rats.

PMID- 17014674
TI  - Strategies to enhance transductional efficiency of adenoviral-based gene transfer
      to primary human fibroblasts and keratinocytes as a platform in dermal wounds.
AB  - Genetically modified keratinocytes and fibroblasts are suitable for delivery of
      therapeutic genes capable of modifying the wound healing process. However,
      efficient gene delivery is a prerequisite for successful gene therapy of wounds.
      Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene
      transfer, their transductional efficiency to cells resident within wounds may
      nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor,
      coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to
      fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads
      to determine enhancement of infectivity. These fiber-modified adenoviral vectors
      included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD),
      polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate
      whether transduction efficiencies of the fiber-modified adenoviral vectors
      correlated with the expression of their putative receptors on keratinocytes and
      fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan
      1, and glypican-1 using quantitative polymerase chain reaction. Analysis of
      luciferase and green fluorescent protein transgene expression showed superior
      transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in
      fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1
      was significantly higher in primary fibroblasts than CAR. In keratinocytes,
      syndecan-1 expression was significantly higher than all the other receptors
      tested. Significant infectivity enhancement was achieved in keratinocytes and
      fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance
      infectivity may help to achieve higher clinical efficacy of wound gene therapy.

PMID- 17014676
TI  - Elucidating the mechanism of wound contraction: rapid versus sustained myosin
      ATPase activity in attached-delayed-released compared with free-floating
      fibroblast-populated collagen lattices.
AB  - Wound contraction closes open wounds by the generation of contractile forces
      within granulation tissue. We investigated the mechanism of wound contraction
      using the in vitro fibroblast-populated collagen lattice (FPCL) contraction
      model. The contraction of the free-floating (FF)-FPCL is through rapid myosin
      ATPase activity, while the contraction of the attached-delayed-released (ADR)
      FPCL is through sustained myosin ATPase activity. All FPCLs were cast identically
      and the contraction of FF-FPCLs was recorded daily for 4 days and the contraction
      of ADR-FPCLs was recorded 1 hour after release on day 4. At day, 4 cell numbers
      were determined and cells undergoing apoptosis were identified and counted.
      Differences in sustained and rapid myosin ATPase activity were shown by added
      inosine triphosphate-induced cell contraction in permeabilized fibroblast
      monolayer preparations. At 2 days, the FF-FPCLs were mostly contracted, while an
      ADR-FPCL completed contraction 1 hour after release at day 4. Contracted
      myofibroblasts, identified by alpha-smooth muscle actin-stained stress fibers,
      were identified in contracted ADR-FPCL, whereas elongated fibroblasts were
      identified in contracted FF-FPCLs. Vanadate inhibited both inosine triphosphate
      induced cell contraction and ADR-FPCL contraction, but neither inhibited ATP
      induced cell contraction or FF-FPCL contraction. Genistein inhibited FF-FPCL
      contraction, but not ADR-FPCL contraction. Advancing tyrosine phosphorylation in
      fibroblasts promotes rapid myosin ATPase activity, while advancing tyrosine
      dephosphorylation in myofibroblasts promotes sustained myosin ATPase. The ADR
      FPCL had a reduced cell count and a greater proportion of cells had entered
      apoptosis compared with FF-FPCL. These experiments show that FF-FPCL contraction
      is through elongated fibroblasts and rapid myosin ATPase, requiring tyrosine
      phosphorylation. In contrast, the mechanism for ADR-FPCL contraction is through
      cell contraction by sustained myosin ATPase, involving tyrosine
      dephosphorylation.

PMID- 17014677
TI  - Prostaglandin E2 differentially modulates human fetal and adult dermal fibroblast
      migration and contraction: implication for wound healing.
AB  - Cyclooxygenase-2 is up-regulated shortly after dermal injury and it has been
      shown to have important activity during the repair process. Its main product in
      the skin, prostaglandin E2 (PGE2), modulates both inflammatory and fibrotic
      processes during wound healing and partially dictates the overall outcome of
      wound healing. PGE2 signaling has been shown to be altered during fetal wound
      healing. This study was designed to examine the mechanism(s) by which PGE2
      regulates fibroblast migration and contraction and to determine whether these
      mechanisms are conserved in fetal-derived dermal fibroblasts. Fetal and adult
      dermal fibroblasts express all four PGE2 receptors. PGE2 inhibits fetal and adult
      fibroblast migration in a dose-dependent manner through the EP2/EP4-cAMP-protein
      kinase A pathway. However, fetal fibroblasts appear to be refractory to this
      effect, requiring a 10-fold higher concentration of PGE2 to achieve a similar
      degree of inhibition as adult fibroblasts. Inhibition of adult fibroblast
      migration correlated with disruption of the actin cytoskeleton. In contrast, PGE2
      or a cAMP analog did not disrupt the actin cytoskeleton of fetal dermal
      fibroblasts. These findings were extended using a modified free-floating,
      fibroblast-populated collagen lattice (FPCL) contraction assay designed to
      measure fibroblast contraction. PGE2-inhibited FPCL contraction by adult
      fibroblasts, but fetal fibroblasts exhibited higher rates of FPCL contraction and
      a blunted response to exogenous modulation by PGE2 or a cyclase activator
      (forskolin). These findings indicate that fetal dermal fibroblasts are partially
      refractory to the effects of PGE2, a major inflammatory mediator associated with
      dermal wound healing. This effect may have significant and specific relevance to
      the scarless fetal wound-healing phenotype.

PMID- 17014678
TI  - The effect of tobacco exposure on the fetal hypothalamic-pituitary-adrenal axis.
AB  - OBJECTIVE: Our objective was to determine if maternal smoking is associated with
      programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Cigarette
      smoking, which induces a state of hypoxia in the fetus, may promote in
      utero'programming' of the HPA axis. In utero, adaptations to the HPA axis, which
      become maladaptive later in life, have been hypothesised to contribute to the
      development of adult cardiovascular disease and metabolic disorders. DESIGN: This
      was a prospective cohort study of term infants. POPULATION AND SETTING: The study
      involved 104 infants born by elective caesarean section, 21 of whom were exposed
      to in utero tobacco and 83 were nonexposed. METHODS: Healthy women with healthy
      pregnancies were recruited if they were undergoing elective caesarean section.
      Maternal blood was drawn for cortisol and cotinine in the morning, and the
      umbilical blood was drawn immediately after delivery of the baby. MAIN OUTCOME
      MEASURES: Umbilical arterial cortisol and adrenocorticotropin hormone (ACTH)
      levels. RESULTS: ACTH levels were significantly elevated in smoke-exposed infants
      [17 (4-22) pmol/l versus 4 (2-11) pmol/l, respectively, P= 0.005], while cortisol
      levels were similar [182 (130-240) nmol/l versus 192 (127-265) nmol/l,
      respectively, P= 0.541]. CONCLUSIONS: For the first time, it was shown that
      infants exposed to in utero tobacco smoke have significantly elevated ACTH levels
      compared with nonexposed infants. The results of this study warrant further
      exploration of the effect of smoking on the neonatal HPA axis as a potential set
      up for 'programming'.

PMID- 17014679
TI  - Chilean women's preferences regarding mode of delivery: which do they prefer and
      why?
AB  - OBJECTIVE: Caesarean section rates in Chile are reported to be as high as 60% in
      some populations. The purpose of this study was to determine pregnant Chilean
      women's preferences towards mode of delivery. DESIGN: Interviewer-administered
      cross-sectional survey. SETTING: Prenatal clinics in Santiago, Chile. Population
      Pregnant women in Santiago, Chile. METHODS: Of 180 women completing the
      questionnaire, 90 were interviewed at a private clinic (caesarean delivery rate
      60%) and 90 were interviewed at a public clinic (cesarean delivery rate 22%).
      Data collected included demographics, preferred mode of delivery, and women's
      attitudes towards vaginal and caesarean deliveries. MAIN OUTCOME MEASURES: Mode
      of delivery preferences, perceptions of mode of delivery measured on a 1-7 Likert
      scale. RESULTS: The majority of women (77.8%) preferred vaginal delivery, 9.4%
      preferred caesarean section, and 12.8% had no preference. There was no
      statistical difference in preference between the public clinic (11% preferred
      caesarean) and the private clinic (8% preferred caesarean, P= 0.74). Overall,
      women preferring caesarean birth were slightly older than other groups (31.6
      years, versus 28.4 years for women who preferred vaginal and 27.3 years for women
      who had no preference, P= 0.05), but there were otherwise no differences in
      parity, income, or education. On a scale of 1-7, women preferring caesarean birth
      rated vaginal birth as more painful, while women preferring vaginal birth rated
      it as less painful (5.8 versus 3.7, P= 0.003). Whether vaginal or caesarean, each
      group felt that their preferred mode of delivery was safer for their baby (P <
      0.001). CONCLUSIONS: Chilean women do not prefer caesarean section to vaginal
      delivery, even in a practice setting where caesarean delivery is more prevalent.
      Thus, women's preferences is unlikely to be the most significant factor driving
      the high caesarean rates in Chile.

PMID- 17014680
TI  - Horizontal transfer of tet(M) and erm(B) resistance plasmids from food strains of
      Lactobacillus plantarum to Enterococcus faecalis JH2-2 in the gastrointestinal
      tract of gnotobiotic rats.
AB  - Two wild-type strains of Lactobacillus plantarum previously isolated from
      fermented dry sausages were analysed for their ability to transfer antibiotic
      resistance plasmids in the gastrointestinal tract. For this purpose, we used
      gnotobiotic rats as an in vivo model. Rats were initially inoculated with the
      recipient Enterococcus faecalis JH2-2 at a concentration of 10(10) CFU mL(-1).
      After a week, either of the two donors L. plantarum DG 522 (harbouring a tet(M)
      containing plasmid of c. 40 kb) or L. plantarum DG 507 [harbouring a tet(M)
      containing plasmid of c. 10 kb and an erm(B)-containing plasmid of c. 8.5 kb] was
      introduced at concentrations in the range of 10(8)-10(10) CFU mL(-1). Two days
      after donor introduction, the first transconjugants (TCs) were detected in faecal
      samples. The detected numbers of tet(M)-TCs were comparable for the two donors.
      In both cases, this number increased to c. 5 x 10(2) CFU g(-1) faeces towards the
      end of the experiment. For erm(B)-TCs, the number was significantly higher and
      increased to c. 10(3) CFU g(-1) faeces. To our knowledge, this is the first study
      showing in vivo transfer of wild-type antibiotic resistance plasmids from L.
      plantarum to E. faecalis.

PMID- 17014681
TI  - Archaeal diversity in Icelandic hot springs.
AB  - Whole-cell density gradient extractions from three solfataras (pH 2.5) ranging in
      temperature from 81 to 90 degrees C and one neutral hot spring (81 degrees C, pH
      7) from the thermal active area of Hveragerethi (Iceland) were analysed for
      genetic diversity and local geographical variation of Archaea by analysis of
      amplified 16S rRNA genes. In addition to the three solfataras and the neutral hot
      spring, 10 soil samples in transects of the soil adjacent to the solfataras were
      analysed using terminal restriction fragment length polymorphism (t-RFLP). The
      sequence data from the clone libraries in combination with 14 t-RFLP profiles
      revealed a high abundance of clones clustering together with sequences from the
      nonthermophilic I.1b group of Crenarchaeota. The archaeal diversity in one
      solfatara was high; 26 different RFLP patterns were found using double digestion
      of the PCR products with restriction enzymes AluI and BsuRI. The sequenced clones
      from this solfatara belonged to Sulfolobales, Thermoproteales or were most
      closest related to sequences from uncultured Archaea. Sequences related to group
      I.1b were not found in the neutral hot spring or the hyperthermophilic solfatara
      (90 degrees C).

PMID- 17014682
TI  - Quatrefoil reentry caused by burst pacing.
AB  - BACKGROUND: Experiments and clinical studies have shown that high-frequency
      (burst) pacing can induce reentry and fibrillation without a strong shock. We
      hypothesize that a train of weak stimuli induces quatrefoil reentry, and
      investigate the mechanism and threshold for this mode of reentry induction.
      METHODS: We apply a train of weak stimuli at different pacing rates to determine
      the threshold necessary to induce quatrefoil reentry. Numerical calculations are
      used to simulate cardiac tissue, based on the bidomain model with unequal
      anisotropy ratios. We consider both anodal and cathodal stimuli. RESULTS:
      Quatrefoil reentry is initiated using much smaller currents during burst pacing
      (0.9 mA) compared to a single premature pulse (8.6 mA). As we varied the pacing
      rate, we observed reentry at the border between different modes of phase locking,
      such as between 1:1 and 2:1 responses. CONCLUSION: Burst pacing can significantly
      reduce the threshold for reentry. However, the extreme sensitivity of reentry
      induction to the exact number of stimuli in the pulse train makes the method
      difficult to use as a consistent, reproducible way to induce reentry.

PMID- 17014683
TI  - Arrhythmogenesis in the developing heart during anoxia-reoxygenation and
      hypothermia-rewarming: an in vitro model.
AB  - INTRODUCTION: The spatio-temporal pattern of arrhythmias in the embryonic/fetal
      heart subjected to a transient hypoxic or hypothermic stress remains to be
      established. METHODS AND RESULTS: Spontaneously beating hearts or isolated atria,
      ventricles, and conotruncus from 4-day-old chick embryos were subjected in vitro
      to 30-minute anoxia and 60-minute reoxygenation. Hearts were also submitted to 30
      minute hypothermia (0-4 degrees C) and 60-minute rewarming. ECG disturbances and
      alterations of atrial and ventricular electromechanical delay (EMD) were
      systematically investigated. Baseline functional parameters were stable during at
      least 2 hours. Anoxia induced tachycardia, followed by bradycardia, atrial
      ectopy, first-, second-, and third-degree atrio-ventricular blocks and, finally,
      transient electromechanical arrest after 6.8 minutes, interquartile ranges (IQR)
      3.1-16.2 (n = 8). Reoxygenation triggered also Wenckebach phenomenon and
      ventricular escape beats. At the onset of reoxygenation QT, PR, and ventricular
      EMD increased by 68%, 70%, and 250%, respectively, whereas atrial EMD was not
      altered. No fibrillations, no ventricular ectopic beats, and no electromechanical
      dissociation were observed. Arrhythmic activity of the isolated atria persisted
      throughout anoxia and upon reoxygenation, whereas activity of the isolated
      ventricles abruptly ceased after 5 minutes of anoxia and resumed after 5 minutes
      of reoxygenation. During hypothermia-rewarming, cardiac activity stopped at 17.9
      degrees C, IQR 16.2-20.6 (n = 4) and resumed at the same temperature with no
      arrhythmias. All preparations fully recovered after 40 minutes of reoxygenation
      or rewarming. CONCLUSION: In the embryonic heart, arrhythmias mainly originated
      in the sinoatrial tissue and resembled those observed in the adult heart.
      Furthermore, oxygen readmission was by far more arrhythmogenic than rewarming and
      the chronotropic, dromotropic, and inotropic effects were fully reversible.

PMID- 17014684
TI  - Tissue Doppler imaging determining the atrial fibrillation cycle length: an
      alternative to the electrophysiologic study or not?

PMID- 17014685
TI  - Transition to wide QRS tachycardia: what is the mechanism?

PMID- 17014686
TI  - Therapeutic treatments potentially mediated by melatonin receptors: potential
      clinical uses in the prevention of osteoporosis, cancer and as an adjuvant
      therapy.
AB  - Melatonin's therapeutic potential is grossly underestimated because its
      functional roles are diverse and its mechanism(s) of action are complex and
      varied. Melatonin produces cellular effects via a variety of mechanisms in a
      receptor independent and dependent manner. In addition, melatonin is a
      chronobiotic agent secreted from the pineal gland during the hours of darkness.
      This diurnal release of melatonin impacts the sensitivity of melatonin receptors
      throughout a 24-hr period. This changing sensitivity probably contributes to the
      narrow therapeutic window for use of melatonin in treating sleep disorders, that
      is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In
      addition to the cyclic changes in melatonin receptors, many genes cycle over the
      24-hr period, independent or dependent upon the light/dark cycle. Interestingly,
      many of these genes support a role for melatonin in modulating metabolic and
      cardiovascular physiology as well as bone metabolism and immune function and
      detoxification of chemical agents and cancer reduction. Melatonin also enhances
      the actions of a variety of drugs or hormones; however, the role of melatonin
      receptors in modulating these processes is not known. The goal of this review is
      to summarize the evidence related to the utility of melatonin as a therapeutic
      agent by focusing on its other potential uses besides sleep disorders. In
      particular, its use in cancer prevention, osteoporosis and, as an adjuvant to
      other therapies are discussed. Also, the role that melatonin and, particularly,
      its receptors play in these processes are highlighted.

PMID- 17014687
TI  - Concentrations of estradiol in ewe cerebrospinal fluid are modulated by
      photoperiod through pineal-dependent mechanisms.
AB  - In the ewe, seasonal anestrus results from an increased responsiveness of the
      hypothalamus to the negative feedback of estradiol (E2) on the gonadotropic axis
      under long-day conditions. However, this seasonal effect could also depend upon
      variable uptake of steroids by the brain. The aim of the present experiment was
      to compare the concentration of E2 in the blood plasma and in the cerebrospinal
      fluid (CSF) from the third ventricle in groups of ovariectomized, estradiol
      treated ewes maintained under short day (SD) or long day (LD) conditions and to
      study the involvement of the pineal gland in this photoperiodic regulation.
      Pinealectomized and sham-operated ewes were equipped with an intracerebral
      cannula to sample the CSF. The plasma E2 concentrations showed no difference
      between LD and SD in sham-operated and pinealectomized animals. In contrast, in
      the CSF, E2 concentration was higher in the LD than the SD group, and
      pinealectomy suppressed this effect of photoperiod. Concomitantly, the
      stimulatory effect of SD on luteinizing hormone levels observed in sham-operated
      ewes was abolished by pinealectomy. The results demonstrate that LD increases the
      E2 concentration in the CSF by a mechanism involving the pineal gland.

PMID- 17014688
TI  - Reduced oxidative damage in ALS by high-dose enteral melatonin treatment.
AB  - Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron
      disease of different etiologies, with oxidative stress as a common molecular
      denominator of disease progression. Melatonin is an amphiphilic molecule with a
      unique spectrum of antioxidative effects not conveyed by classical antioxidants.
      In preparation of a possible future clinical trial, we explored the potential of
      melatonin as neuroprotective compound and antioxidant in: (1) cultured
      motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)
      transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that
      melatonin attenuates glutamate-induced cell death of cultured motoneurons. In
      SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression
      and extended survival. In a clinical safety study, chronic high-dose (300 mg/day)
      rectal melatonin was well tolerated during an observation period of up to 2 yr.
      Importantly, circulating serum protein carbonyls, which provide a surrogate
      marker for oxidative stress, were elevated in ALS patients, but were normalized
      to control values by melatonin treatment. This combination of preclinical
      effectiveness and proven safety in humans suggests that high-dose melatonin is
      suitable for clinical trials aimed at neuroprotection through antioxidation in
      ALS.

PMID- 17014689
TI  - Modulation of melatonin receptors and G-protein function by microtubules.
AB  - Chronic melatonin exposure produces microtubule rearrangements in Chinese hamster
      ovary (CHO) cells expressing the human MT1 melatonin receptor while at the same
      time desensitizing MT1 receptors. Because microtubule rearrangements parallel MT1
      receptor desensitization, we tested whether microtubules modulate receptor
      responsiveness. We determined whether depolymerization of microtubules by
      Colcemid, which prevents melatonin-induced outgrowths in MT1-expressing CHO
      cells, also prevents MT1 receptor desensitization by affecting G(alpha)-GTP
      exchange on G-proteins. In this study, we found that depolymerization of
      microtubules in MT1 receptor expressing cells, prevented melatonin-induced
      receptor desensitization reflected by an increase in the number of high potency
      sites when compared with melatonin-treated cells. Further examination of the
      mechanism(s) underlying this desensitization suggested that these effects
      occurred at the level of G-proteins. Depolymerization of microtubules during
      melatonin-induced desensitization, attenuated forskolin-induced cAMP
      accumulation, the opposite of which usually occurs following melatonin exposure
      alone. Concomitant to this attenuation in the forskolin response was a reduction
      in the amount of G(i alpha) protein coupled to MT1 receptors and an increase in
      [32P] azidoanilido GTP incorporation into G(i) proteins. These data are
      consistent with the findings that microtubule depolymerization did not affect
      MT1/G(q) coupling nor did it affect melatonin-induced phosphoinositide hydrolysis
      following melatonin exposure. However, interestingly, microtubule
      depolymerization enhanced melatonin-induced protein kinase C activation that was
      blocked in the presence of pertussis toxin. These data demonstrate that
      microtubule dynamics can modulate melatonin receptor function through their
      actions on G(i) proteins and impact on downstream signaling cascades.

PMID- 17014690
TI  - Preclinical evaluation of pharmacokinetics and safety of melatonin in propylene
      glycol for intravenous administration.
AB  - Melatonin is a highly effective treatment in different animal models of
      excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability,
      commercial sponsors are not interested in funding clinical evaluations of
      melatonin. Investigators may initiate small-scale clinical evaluation, and
      intravenous (i.v.) administration is appropriate in acute stroke patients.
      Institutional Review Boards may require proper preclinical evaluation of the
      preparation. In this pharmacokinetic and safety study, melatonin in propylene
      glycol was evaluated in adult male Sprague-Dawley rats. Following a single i.v.
      injection at 5 or 15 mg/kg, plasma concentrations of melatonin increased to 39
      and 199 million pg/mL at 2 min and 128,000 and 772,000 pg/mL at 120 min. Within
      60 min of injection, the blood pressure, heart rate and body temperature remained
      unaffected. Melatonin at 5 mg/kg did not influence the complete blood counts at
      60 min, but melatonin at 15 mg/kg had some effects on the differential white cell
      and platelet counts. Melatonin at 5 or 15 mg/kg slightly elevated some liver
      enzymes at 60 min of injection, and melatonin at higher dose also elevated plasma
      creatinine and lactate dehydrogenase levels. At 24 hr after completion of six
      daily injections of melatonin, there was a 5.5% reduction in body weight. Gross
      postmortem examination and histological examination of the brain, kidney, liver
      and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in
      propylene glycol markedly elevates plasma levels of melatonin with no serious
      toxicity. This preparation should be further evaluated in human patients.

PMID- 17014691
TI  - Effect of TNF-alpha on the melatonin synthetic pathway in the rat pineal gland:
      basis for a 'feedback' of the immune response on circadian timing.
AB  - A retino-hypothalamic-sympathetic pathway drives the nocturnal surge of pineal
      melatonin production that determines the synchronization of pineal function with
      the environmental light/dark cycle. In many studies, melatonin has been
      implicated in the modulation of the inflammatory response. However, scant
      information on the feedback action of molecules present in the blood on the
      pineal gland during the time course of an inflammatory response is available.
      Here we analyzed the effect of tumor necrosis factor-alpha (TNF-alpha) and
      corticosterone on the transcription of the Aa-nat, hiomt and 14-3-3 protein genes
      in denervated pineal glands of rats stimulated for 5 hr with norepinephrine,
      using real-time reverse transcription-polymerase chain reaction. The
      transcription of Aa-nat, a gene encoding the key enzyme in melatonin
      biosynthesis, together with the synthesis of the melatonin precursor N
      acetylserotonin, was inhibited by TNF-alpha. This inhibition was transient, and a
      preincubation of TNF-alpha for more than 24 hr had no detectable effect. In fact,
      a protein(s) transcribed, later on, as shown by cycloheximide, was responsible
      for the reversal of the inhibition of Aa-nat transcription. In addition,
      corticosterone induced a potentiation of norepinephrine-induced Aa-nat
      transcription even after 48 hr of incubation. These data support the hypothesis
      that the nocturnal surge in melatonin is impaired at the beginning of an
      inflammatory response and restored either during the shutdown of an acute
      response or in a chronic inflammatory pathology. Here, we introduce a new
      molecular pathway involved in the feedback of an inflammatory response on pineal
      activity, and provide a molecular basis for understanding the expression of
      circadian timing in injured organisms.

PMID- 17014693
TI  - Effect and mechanism of melatonin's action on the proliferation of human
      umbilical vein endothelial cells.
AB  - Melatonin is the major secretory product of the pineal gland and is considered an
      important natural oncostatic agent. The anticancer activity of melatonin is due
      to its immunomodulatory, anti-proliferative and antioxidative effects. At present
      there are no direct data available as to melatonin's possible influence on
      angiogenesis, which is a major biological mechanism responsible for tumor growth
      and dissemination. The current study investigated the influence of melatonin on
      angiogenesis. Human umbilical vein endothelial cells (HUVECs) were cultured,
      identified, and purified. Cell growth and viability, DNA fragmentation and cell
      cycle analyses were determined. To elucidate the mechanism of action of
      melatonin, Western blot analyses for P53, Bax and Bcl-2 expression were carried
      out. The results demonstrate the anti-proliferative and apoptosis-inducing
      effects of melatonin; these changes were associated with cell cycle arrest,
      upregulation of P53 and Bax and downregulation of Bcl-2. Taken together, our data
      showed that melatonin in high concentrations markedly reduces HUVECs
      proliferation, induces cellular apoptosis, and modulates cell cycle length. P53
      and Bax/Bcl-2 expression changes may be involved in these actions of melatonin.

PMID- 17014692
TI  - Comparison of 6-hydroxylmelatonin or melatonin in protecting neurons against
      ischemia/reperfusion-mediated injury.
AB  - The protective effect of exogenous melatonin or 6-hydroxylmelatonin on neurons
      was examined in N2a cells following exposure to oxygen-glucose-serum deprivation
      insults. After N2a cells cultured in vitro were deprived of glucose, serum and
      oxygen for 90 min, the different concentrations of melatonin or 6
      hydroxylmelatonin were added to the medium. Then, treated cells were cultured for
      different intervals. At the end of the treatment, the collected culture solution
      was used for the analysis of the activity of lactate dehydrogenase (LDH) and the
      cells were used for the examination of the following parameters: cell viability
      (MTT), DNA fragmentation, reactive oxygen species (ROS) production, mitochondrial
      transmembrane potential, cytochrome C and caspase 3 activity. The results show
      that melatonin and 6-hydroxylmelatonin both reduced oxygen-glucose-serum
      deprivation-mediated N2a cell apoptosis, but they could not completely inhibit
      the apoptosis of the cells and the inhibitory effect of melatonin was stronger
      than that of 6-hydroxylmelatonin. Both of them could inhibit LDH and cytochrome C
      release and caspase 3 activity. Although 6-hydroxylmelatonin could no longer
      maintain mitochondrial transmembrane potential 6 h after reperfusion, its
      inhibitory effect on cytochrome C release from mitochondria and the scavenging
      role of ROS were stronger than those of melatonin. Moreover, melatonin promoted
      ROS production at the 15th min of the reperfusion, and then it began to remove
      ROS from cells. Our study showed that melatonin and 6-hydroxylmelatonin can be
      used as supplements in the treatment of neurological disorders involving
      oxidative stress. Melatonin serves as more than a ROS scavenger and its other
      roles await further study.

PMID- 17014694
TI  - Melatonin modulates signal transduction pathways and apoptosis in experimental
      colitis.
AB  - Various evidences have documented that the pineal secretory product melatonin
      exerts an important anti-inflammatory effect in different experimental models
      including colitis. The aim of the present study was to evaluate whether melatonin
      regulates the inflammatory response of experimental colitis in rats at the level
      of signal transduction pathway. Colitis was induced by intracolonic instillation
      of dinitrobenzene sulfonic acid (DNBS). Four days after DNBS administration, a
      substantial increase of colon TNF-alpha production was associated with the colon
      damage. In DNBS-treated rats, the colon injury correlated with a significant rise
      of apoptosis (evaluated by TUNEL coloration) which was associated with a
      significant increased expression of proapoptotic Bax and decreased colon content
      of antiapoptotic Bcl-2. This inflammatory response was also related to activation
      of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun as well as FAS
      ligand expression in the colon. Treatment with melatonin (15 mg/kg daily i.p.)
      was associated with a remarkable amelioration of colonic disrupted architecture
      as well as a significant reduction of TNF-alpha. Melatonin also reduced the NF
      kappaB activation and phosphorylation of c-Jun as well as the Fas ligand
      expression in the colon. Furthermore, melatonin reduced the expression of Bax and
      prevented the loss of Bcl-2 proteins as well as the presence of apoptotic cells
      caused by DNBS. The results of this study show that melatonin administration
      exerts beneficial effects in inflammatory bowel disease by modulating signal
      transduction pathways.

PMID- 17014695
TI  - Interactions of melatonin and its metabolites with the ABTS cation radical:
      extension of the radical scavenger cascade and formation of a novel class of
      oxidation products, C2-substituted 3-indolinones.
AB  - Melatonin had previously been shown to reduce up to four 2,2'-azino-bis-(3
      ethylbenzthiazoline-6-sulfonic acid) cation radicals (ABTS*+) via a scavenger
      cascade ending with N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). However, when
      melatonin is added to the reaction system in much lower quantities than ABTS*+,
      the number of radicals scavenged per melatonin molecule is considerably higher
      and can attain a value of ten. Under conditions allowing for such a
      stoichiometry, novel products have been detected which derive from AFMK (1).
      These were separated by repeated chromatography and the major compounds were
      characterized by spectroscopic methods, such as mass spectrometry (HPLC-MS, EI-MS
      and ESI-HRMS), 1H nuclear magnetic resonance (NMR) and 13C NMR, heteronuclear
      multiple bond connectivity (HMBC) correlations. The identified substances are
      formed by re-cyclization and represent 3-indolinones carrying the side chain at
      C2; the N-formyl group can be maintained, but deformylated analogs seem to be
      also generated, according to MS. The primary product from AFMK (1) is N-(1-formyl
      5-methoxy-3-oxo-2,3-dihydro-1H-indol-2-ylidenemethyl)-acetamide (2), which is
      obtained after purification as E- and Z-isomers (2a, 2b); a secondary product has
      been identified as N-(1-formyl-2-hydroxy-5-methoxy-3-oxo-2,3-dihydro-1H-indol-2
      ylmethyl)-acetamide (3). When H2O2 is added to the ABTS*+ reaction mixture in
      quantities not already leading to substantial reduction of this radical, compound
      3 is isolated as the major product, whereas 2a and 2b are virtually absent. The
      substances formed differ from all previously known oxidation products which
      derive from melatonin and are, among these, the first 3-indolinones. Moreover,
      the aliphatic side chain at C2 is reminiscent of other substances which have been
      synthesized in the search for melatonin receptor ligands.

PMID- 17014696
TI  - Mechanisms involved in the antinociception caused by melatonin in mice.
AB  - The present study assesses the antinociceptive effect of melatonin in chemical
      behavioral models of nociception and investigates some of the mechanisms
      underlying this effect. Melatonin administered by intraperitoneal (i.p., 10-100
      mg/kg), intracerebroventricular (i.c.v., 250-500 pmol/site) and intraplantar
      (i.pl., 30-100 ng/i.pl.) routes, reduced in a dose-dependent manner the
      nociception caused by i.pl. injection of glutamate (10 micromol/paw), with mean
      ID50 values of 32.6 mg/kg, 200 pmol/site and 59 ng/i.pl., respectively.
      Furthermore, melatonin in the dose range of 10-100 mg/kg, i.p., reduced the
      neurogenic pain caused by i.pl. injection of capsaicin (5.2 nmol/paw) with
      inhibition of 48 +/- 4%. The antinociceptive effect of melatonin (100 mg/kg,
      i.p.) on glutamate-induced nociception was completely prevented by the
      pretreatment of animals with naloxone (a nonselective opioid receptor antagonist,
      1 mg/kg, i.p.), ketanserin (a preferential 5-HT2A receptor antagonist, 1 mg/kg,
      i.p.), sulpiride (a D2 receptor antagonist, 50 mg/kg, i.p.), L-arginine (a
      precursor of nitric oxide, 600 mg/kg, i.p.), yohimbine (an alpha2-adrenoceptor
      antagonist, 0.15 mg/kg, i.p.) and luzindole (a preferential MT2 receptor
      antagonist, 10 mg/kg, i.p.), but was not affected by the pretreatment with D
      arginine (an inactive isomer of L-arginine, 600 mg/kg, i.p.), prazosin (an alpha1
      adrenoceptor antagonist, 0.15 mg/kg, i.p.) or after bilateral adrenalectomy.
      Collectively, present results suggest that melatonin produces peripheral and
      central antinociception when assessed on capsaicin- or glutamate-induced pain in
      mice through mechanisms that are likely mediated by interaction with plasma
      membrane-bound melatonin receptors and modulated by opioid, serotonergic (5-HT2A
      receptors), dopaminergic (D2-receptors), adrenergic (alpha2-adrenoceptors)
      systems as well as the L-arginine-nitric oxide pathway.

PMID- 17014697
TI  - Maurer's clefts-restricted localization, orientation and export of a Plasmodium
      falciparum RIFIN.
AB  - RIFINs are clonally variant antigens expressed in Plasmodium falciparum.
      Transfection and the green fluorescence protein (GFP) tagged either internally or
      C-terminally to the 3D7 PFI0050c RIFIN gene product were used to investigate
      protein localization, orientation and trafficking. Green fluorescence pattern
      emerging from live transfectant parasites expressing each of the RIFIN-GFP
      chimera was different. The internally GFP-tagged protein was exported to Maurer's
      clefts (MC) in the erythrocyte cytosol, whereas the C-terminally GFP-tagged full
      length RIFIN chimera was not trafficked out of the parasite. Interestingly, when
      some RIFIN-specific C-terminal amino acid sequences were removed, the resulting
      truncated molecule reached the MC. Using anti-RIFIN and anti-GFP antibodies to
      probe both live and fixed transfectants, staining was confined to MC and was not
      detected on the erythrocyte surface, a location previously suggested for this
      protein family. From selective permeabilization experiments, the highly variable
      portion of the RIFIN-GFP-insertion chimera appeared to be exposed to the
      erythrocyte cytosol, presumably anchored in the MC membrane via the two
      transmembrane domains. Trafficking of both chimeras in young ring stages was
      sensitive to Brefeldin A (BFA), although older rings showed differential
      sensitivity to BFA.

PMID- 17014698
TI  - Imaging clathrin dynamics in Drosophila melanogaster hemocytes reveals a role for
      actin in vesicle fission.
AB  - Clathrin-mediated endocytosis (CME) is essential for maintaining many basic
      cellular processes. We monitored the dynamics of clathrin in live Drosophila
      melanogaster hemocytes overexpressing clathrin light chain fused to enhanced
      green fluorescent protein (EGFP) using evanescent wave microscopy. Membrane
      associated clathrin-coated structures (CCS) constitutively appeared at the
      peripheral filopodial membrane, moved centripetally while growing in intensity,
      before being eventually endocytosed within a few tens of seconds. This directed
      CCS traffic was independent of microtubules but could be blocked by latrunculin
      A. Taking advantage of available mutants of Drosophila, we expressed clathrin
      EGFP in wasp and shibire mutant backgrounds to study the role of actin and
      dynamin in CCS dynamics and CME in hemocytes. We show that actin plays an
      essential role in CME in these cells, and that actin and dynamin act at the same
      stage, but independent of each other. Drosophila melanogaster hemocytes proved to
      be a promising model system to uncover the molecular events during CME in
      combining live-cell imaging and genetic analysis.

PMID- 17014699
TI  - Ultrastructural analysis of ESCRT proteins suggests a role for endosome
      associated tubular-vesicular membranes in ESCRT function.
AB  - The endosomal sorting complex required for transport (ESCRT) is thought to
      support the formation of intralumenal vesicles of multivesicular bodies (MVBs).
      The ESCRT is also required for the budding of HIV and has been proposed to be
      recruited to the HIV-budding site, the plasma membrane of T cells and MVBs in
      macrophages. Despite increasing data on the function of ESCRT, the
      ultrastructural localization of its components has not been determined. We
      therefore localized four proteins of the ESCRT machinery in human T cells and
      macrophages by quantitative electron microscopy. All the proteins were found
      throughout the endocytic pathway, including the plasma membrane, with only around
      10 and 3% of the total labeling in the cytoplasm and on the MVBs, respectively.
      The majority of the labeling (45%) was unexpectedly found on tubular-vesicular
      endosomal membranes rather than on endosomes themselves. The ESCRT labeling was
      twice as concentrated on early and late endosomes/lysosomes in macrophages
      compared with that in T cells, where it was twice more abundant at the plasma
      membrane. The ESCRT proteins were not redistributed on HIV infection, suggesting
      that the amount of ESCRT proteins located at the budding site suffices for HIV
      release. These results represent the first systematic ultrastructural
      localization of ESCRT and provide insights into its role in uninfected and HIV
      infected cells.

PMID- 17014701
TI  - Response of biotic communities to salinity changes in a Mediterranean hypersaline
      stream.
AB  - BACKGROUND: This study investigates the relationship between salinity and biotic
      communities (primary producers and macroinvertebrates) in Rambla Salada, a
      Mediterranean hypersaline stream in SE Spain. Since the 1980's, the mean salinity
      of the stream has fallen from about 100 g L(-1) to 35.5 g L(-1), due to intensive
      irrigated agriculture in the watershed. Furthermore, large dilutions occur
      occasionally when the water irrigation channel suffers cracks. RESULTS: Along the
      salinity gradient studied (3.5-76.4 g L(-1)) Cladophora glomerata and Ruppia
      maritima biomass decreased with increasing salinity, while the biomass of
      epipelic algae increased. Diptera and Coleoptera species dominated the community
      both in disturbed as in re-established conditions. Most macroinvertebrates
      species found in Rambla Salada stream are euryhaline species with a broad range
      of salinity tolerance. Eight of them were recorded in natural hypersaline
      conditions (approximately 100 g L(-1)) prior to important change in land use of
      the watershed: Ephydra flavipes, Stratyomis longicornis, Nebrioporus ceresyi, N.
      baeticus, Berosus hispanicus, Enochrus falcarius, Ochthebius cuprescens and
      Sigara selecta. However, other species recorded in the past, such as Ochthebius
      glaber, O. notabilis and Enochrus politus, were restricted to a hypersaline
      source or absent from Rambla Salada. The dilution of salinity to 3.5-6.8 g L(-1)
      allowed the colonization of species with low salininty tolerance, such as
      Melanopsis praemorsa, Anax sp., Simulidae, Ceratopogonidae and Tanypodinae. The
      abundance of Ephydra flavipes and Ochthebius corrugatus showed a positive
      significant response to salinity, while Anax sp., Simulidae, S. selecta, N.
      ceresyi, N. baeticus, and B. hispanicus showed significant negative correlations.
      The number of total macroinvertebrate taxa, Diptera and Coleoptera species,
      number of families, Margalef's index and Shannon's diversity index decreased with
      increasing salinity. However, the rest of community parameters, such as the
      abundance of individuals, evenness and Simpson's index, showed no significant
      response to changes in salinity. Classification and ordination analysis revealed
      major differences in macroinvertebrate community structure between hypersaline
      conditions (76.4 g L(-1)) and the rest of the communities observed at the lower
      salinity levels, and revealed that below approximately 75 g L(-1),
      dissimilarities in the communities were greater between the two habitats studied
      (runs and pools) than between salinity levels. CONCLUSION: Salinity was the first
      factor determining community composition and structure in Rambla Salada stream
      followed by the type of habitat.

PMID- 17014700
TI  - Characterization of neutralizing epitopes within the major capsid protein of
      human papillomavirus type 33.
AB  - BACKGROUND: Infections with papillomaviruses induce type-specific immune
      responses, mainly directed against the major capsid protein, L1. Based on the
      propensity of the L1 protein to self-assemble into virus-like particles (VLPs),
      type-specific vaccines have already been developed. In order to generate vaccines
      that target a broader spectrum of HPV types, extended knowledge of neutralizing
      epitopes is required. Despite the association of human papillomavirus type 33
      (HPV33) with cervical carcinomas, fine mapping of neutralizing conformational
      epitopes on HPV33 has not been reported yet. By loop swapping between HPV33 and
      HPV16 capsid proteins, we have identified amino acid sequences critical for the
      binding of conformation-dependent type-specific neutralizing antibodies to
      surface-exposed hyper variable loops of HPV33 capsid protein L1. RESULTS:
      Reactivities of monoclonal antibodies (mAbs) H33.B6, H33.E12, H33.J3 and H16.56E
      with HPV16:33 and HPV33:16 hybrid L1 VLPs revealed the complex structures of
      their conformational epitopes as well as the major residues contributing to their
      binding sites. Whereas the epitope of mAb H33.J3 was determined by amino acids
      (aa) 51-58 in the BC loop of HPV33 L1, sequences of at least two hyper variable
      loops, DE (aa 132-140) and FGb (aa 282-291), were found to be essential for
      binding of H33.B6. The epitope of H33.E12 was even more complex, requiring
      sequences of the FGa loop (aa 260-270), in addition to loops DE and FGb.
      CONCLUSION: These data demonstrate that neutralizing epitopes in HPV33 L1 are
      mainly located on the tip of the capsomere and that several hyper variable loops
      contribute to form these conformational epitopes. Knowledge of the antigenic
      structure of HPV is crucial for designing hybrid particles as a basis for
      intertypic HPV vaccines.

PMID- 17014702
TI  - Employment status and differences in the one-year coverage of physician visits:
      different needs or unequal access to services?
AB  - BACKGROUND: The dichotomy employed vs. unemployed is still a relevant, but rather
      crude measure of status in current labour markets. Also, studies concerning the
      association of employment status with health have to specify the type of the
      employment as well as the characteristics of the unemployment. This study aims to
      reveal differences and potential inequalities in physician visits among seven
      groups in the core-periphery structures of the labour markets. METHODS: A total
      of 16,000 Finns responded to a postal survey in 2003. Their visits to physicians
      in public primary health care, occupational health care, private health services,
      hospital outpatient clinics and dental care services during previous year were
      measured as indicators of service utilisation. Participants were classified as
      employees having a permanent or fixed-term and full-time or part-time contract
      and as those experiencing short-term, prolonged or long-term unemployment.
      Differences in the one-year coverage of physician visits between these groups of
      employees were analysed using logistic regression analyses where differences in
      the need for services were controlled for by including demographics and self
      rated health assessments in the models. RESULTS: Permanently employed respondents
      had visited a physician most often, and the need-adjusted regression models
      showed significantly lower odds ratios for a visit among fixed-term employees (OR
      0.65, 95% CI 0.53-0.81) and in particular among the long-term unemployed (OR
      0.21, 95% CI 0.14-0.31). A stratified analysis according to health care sector
      showed the lowest odds ratios in occupational health care and private physicians
      (ORs between 0.05 and 0.73) and also low odds ratios for dentists (ORs between
      0.45 and 0.91), whereas visits to public primary health care were more common
      among non-permanent employees and the unemployed (ORs between 1.46 and 2.39).
      CONCLUSION: The use of physician services varies according to labour market
      status, being relatively low among the non-permanently employed and the
      unemployed. This underuse is emphasised when clinical need is taken into account.
      The main reasons for the variance evidently lie in the structures of the Finnish
      health service system. The result may indicate non-optimal health care of the
      population on the periphery of the labour market, but it may also reflect the
      importance of employment status as a context for need and the decision to visit a
      physician.

PMID- 17014703
TI  - Establishment of the epithelial-specific transcriptome of normal and malignant
      human breast cells based on MPSS and array expression data.
AB  - INTRODUCTION: Diverse microarray and sequencing technologies have been widely
      used to characterise the molecular changes in malignant epithelial cells in
      breast cancers. Such gene expression studies to identify markers and targets in
      tumour cells are, however, compromised by the cellular heterogeneity of solid
      breast tumours and by the lack of appropriate counterparts representing normal
      breast epithelial cells. METHODS: Malignant neoplastic epithelial cells from
      primary breast cancers and luminal and myoepithelial cells isolated from normal
      human breast tissue were isolated by immunomagnetic separation methods. Pools of
      RNA from highly enriched preparations of these cell types were subjected to
      expression profiling using massively parallel signature sequencing (MPSS) and
      four different genome wide microarray platforms. Functional related transcripts
      of the differential tumour epithelial transcriptome were used for gene set
      enrichment analysis to identify enrichment of luminal and myoepithelial type
      genes. Clinical pathological validation of a small number of genes was performed
      on tissue microarrays. RESULTS: MPSS identified 6,553 differentially expressed
      genes between the pool of normal luminal cells and that of primary tumours
      substantially enriched for epithelial cells, of which 98% were represented and
      60% were confirmed by microarray profiling. Significant expression level changes
      between these two samples detected only by microarray technology were shown by
      4,149 transcripts, resulting in a combined differential tumour epithelial
      transcriptome of 8,051 genes. Microarray gene signatures identified a
      comprehensive list of 907 and 955 transcripts whose expression differed between
      luminal epithelial cells and myoepithelial cells, respectively. Functional
      annotation and gene set enrichment analysis highlighted a group of genes related
      to skeletal development that were associated with the myoepithelial/basal cells
      and upregulated in the tumour sample. One of the most highly overexpressed genes
      in this category, that encoding periostin, was analysed immunohistochemically on
      breast cancer tissue microarrays and its expression in neoplastic cells
      correlated with poor outcome in a cohort of poor prognosis estrogen receptor
      positive tumours. CONCLUSION: Using highly enriched cell populations in
      combination with multiplatform gene expression profiling studies, a comprehensive
      analysis of molecular changes between the normal and malignant breast tissue was
      established. This study provides a basis for the identification of novel and
      potentially important targets for diagnosis, prognosis and therapy in breast
      cancer.

PMID- 17014704
TI  - Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced
      inflammatory skin lesions in systemic lupus erythematosus?
AB  - Apoptotic cells are thought to play an essential role in the pathogenesis of
      systemic lupus erythematosus (SLE). We hypothesise that delayed or altered
      clearance of apoptotic cells after UV irradiation will lead to inflammation in
      the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated
      with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB).
      Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days,
      for numbers of apoptotic cells, T cells, macrophages, and deposition of
      immunoglobulin and complement. Additionally, to compare results with cutaneous
      lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions
      were analysed morphologically for apoptotic cells and infiltrate. Clearance rate
      of apoptotic cells after irradiation did not differ between patients and
      controls. Influx of macrophages in dermal and epidermal layers was significantly
      increased in patients compared with controls. Five out of 15 patients developed a
      dermal infiltrate that was associated with increased epidermal influx of T cells
      and macrophages but not with numbers of apoptotic cells or epidermal deposition
      of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies.
      Inflammatory lesions in these patients were localised near accumulations of
      apoptotic keratinocytes similar as was seen in the majority of LE skin lesions.
      In vivo clearance rate of apoptotic cells is comparable between SLE patients and
      controls. However, the presence of inflammatory lesions in the vicinity of
      apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE
      patients, suggests that these lesions result from an inflammatory clearance of
      apoptotic cells.

PMID- 17014705
TI  - Multiple endocrine neoplasia type 1.
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant
      hereditary cancer syndrome presented mostly by tumours of the parathyroids,
      endocrine pancreas and anterior pituitary, and characterised by a very high
      penetrance and an equal sex distribution. It occurs in approximately one in
      30,000 individuals. Two different forms, sporadic and familial, have been
      described. The sporadic form presents with two of the three principal MEN1
      related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and
      pituitary tumours) within a single patient, while the familial form consists of a
      MEN1 case with at least one first degree relative showing one of the endocrine
      characterising tumours. Other endocrine and non-endocrine lesions, such as
      adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and
      thymus, lipomas, angiofibromas, collagenomas have been described. The responsible
      gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein,
      menin, with no sequence homology to other known human proteins. MEN1 syndrome is
      caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is
      probably involved in the regulation of several cell functions such as DNA
      replication and repair and transcriptional machinery. The combination of clinical
      and genetic investigations, together with the improving of molecular genetics
      knowledge of the syndrome, helps in the clinical management of patients.
      Treatment consists of surgery and/or drug therapy, often in association with
      radiotherapy or chemotherapy. Currently, DNA testing allows the early
      identification of germline mutations in asymptomatic gene carriers, to whom
      routine surveillance (regular biochemical and/or radiological screenings to
      detect the development of MEN1-associated tumours and lesions) is recommended.

PMID- 17014706
TI  - Low carbohydrate diets in family practice: what can we learn from an internet
      based support group.
AB  - The Active Low-Carber Forums (ALCF) is an on-line support group started in 2000
      which currently has more than 86,000 members. Data collected from posts to the
      forum and from an on-line survey were used to determine the behavior and
      attitudes of people on low carbohydrate diets. Members were asked to complete a
      voluntary 27-item questionnaire over the internet. Our major findings are as
      follows: survey respondents, like the membership at large, were mostly women and
      mostly significantly overweight, a significant number intending to and, in many
      cases, succeeding at losing more than 100 lbs. The great majority of members of
      ALCF identify themselves as following the Atkins diet or some variation of it.
      Although individual posts on the forum and in the narrative part of our survey
      are critical of professional help, we found that more than half of respondents
      saw a physician before or during dieting and, of those who did, about half
      received support from the physician. Another 28 % found the physician initially
      neutral but supportive after positive results were produced. Using the same
      criteria as the National Weight Registry (without follow-up)--30 lbs or more lost
      and maintained for more than one year--it was found that more than 1400 people
      had successfully used low carb methods. In terms of food consumed, the perception
      of more than half of respondents were that they ate less than before the diet and
      whereas high protein, high fat sources replaced carbohydrate to some extent, the
      major change indicated by survey-takers is a large increase in green vegetables
      and a large decrease in fruit intake. Government or health agencies were not
      sources of information for dieters in this group and a collection of narrative
      comments indicates a high level of satisfaction, indeed enthusiasm for low
      carbohydrate dieting. The results provide both a tabulation of the perceived
      behavior of a significant number of dieters using low carbohydrate strategies as
      well as a collection of narratives that provide a human perspective on what it is
      like to be on such a diet. An important conclusion for the family physician is
      that it becomes possible to identify a diet that is used by many people where the
      primary principle is replacement of starch and sugar-containing foods with non
      starchy vegetables, with little addition of fat or protein. Used by many people
      who identify themselves as being on the Atkins diet, such a strategy provides the
      advantages of carbohydrate-restricted diets but is less iconoclastic than the
      popular perception and therefore more acceptable to traditional nutritionists. It
      is reasonable for family practitioners to turn this observation into a
      recommendation for patients for weight control and other health problems.

PMID- 17014707
TI  - In vitro susceptibilities of Brucella melitensis isolates to eleven antibiotics.
AB  - BACKGROUND: Brucellosis is an endemic disease present in many countries
      worldwide, but it is rare in Europe and North America. Nevertheless brucella is
      included in the bacteria potentially used for bioterrorism. The aim of this study
      was the investigation of the antibiotic susceptibility profile of brucella
      isolates from areas of the eastern Mediterranean where it has been endemic.
      METHODS: The susceptibilities of 74 Brucella melitensis isolates derived from
      clinical samples (57) and animal products (17) were tested in vitro. The strains
      originate from Crete (59), Cyprus (10), and Syria (5). MICs of tetracycline,
      rifampicin, streptomycin, gentamicin, norfloxacin, ciprofloxacin, levofloxacin,
      trimethoprim/sulfamethoxazole, ampicillin, amoxicillin/clavulanic acid, and
      erythromycin were detected by E-test method. The NCCLS criteria for slow growing
      bacteria were considered to interpret the results. RESULTS: All the isolates were
      susceptible to tetracycline, streptomycin, gentamicin, ciprofloxacin,
      norfloxacin, and levofloxacin. Two isolates presented reduced susceptibility to
      rifampicin (MIC value: 1.5 mg/l) and eight to SXT (MIC values: 0.75-1.5 mg/l).
      Erythromycin had the highest (4 mg/l) MIC90value and both norfloxacin and
      erythromycin the highest (1.5 mg/l) MIC50 value. CONCLUSION: Brucella isolates
      remain susceptible in vitro to most antibiotics used for treatment of
      brucellosis. The establishment of a standardized antibiotic susceptibility method
      for Brucella spp would be useful for resistance determination in these bacteria
      and possible evaluation of bioterorism risks.

PMID- 17014708
TI  - Chemotherapy followed by low dose radiotherapy in childhood Hodgkin's disease:
      retrospective analysis of results and prognostic factors.
AB  - PURPOSE: To report the treatment results and prognostic factors of childhood
      patients with Hodgkin's disease treated with chemotherapy (CT) followed by low
      dose radiotherapy (RT). PATIENTS AND METHODS: This retrospective series analyzed
      166 patients under 18 years old, treated from January 1985 to December 2003.
      Median age was 10 years (range 2-18). The male to female ratio was 2,3 : 1.
      Lymphonode enlargement was the most frequent clinical manifestation (68%), and
      the time of symptom duration was less than 6 months in 55% of the patients. In
      histological analysis Nodular Sclerosis was the most prevalent type (48%)
      followed by Mixed Celularity (34.6%). The staging group according Ann Arbor
      classification was: I (11.7%), II (36.4%), III (32.1%) and IV (19.8%). The
      standard treatment consisted of chemotherapy multiple drug combination according
      the period of treatment protocols vigent: ABVD in 39% (n-65) of the cases, by
      VEEP in 13 %(n-22), MOPP in 13 %(n-22), OPPA-13 %(n-22) and ABVD/OPPA in 22 %(n
      33). Radiotherapy was device to all areas of initial presentation of disease.
      Dose less or equal than 21 Gy was used in 90.2% of patients with most part of
      them (90%) by involved field (IFRT) or mantle field. RESULTS: The OS and EFS in
      10 years were 89% and 87%. Survival according to clinical stage as 94.7%, 91.3%,
      82.3% and 71% for stages I to IV(p = 0,005). The OS was in 91.3% of patients who
      received RT and in 72.6% of patients who did not (p = 0,003). Multivariate
      analysis showed presence of B symptoms, no radiotherapy and advanced clinical
      stage to be associated with a worse prognosis. CONCLUSION: This data
      demonstrating the importance of RT consolidation with low dose and reduced
      volume, in all clinical stage of childhood HD, producing satisfactory ten years
      OS and EFS. As the disease is highly curable, any data of long term follow-up
      should be presented in order to better direct therapy, and to identify groups of
      patients who would not benefit from radiation treatment.

PMID- 17014709
TI  - Expression of platelet derived growth factor family members and the potential
      role of imatinib mesylate for cervical cancer.
AB  - BACKGROUND: Despite significant achievements in the treatment of cervical cancer,
      it is still a deadly disease; hence newer therapeutical modalities are needed.
      Preliminary investigations suggest that platelet-derived growth factor (PDGF)
      might have a role in the development of cervical cancer, therefore it is
      important to determine whether this growth factor pathway is functional and its
      targeting with imatinib mesylate leads to growth inhibition of cervical cancer
      cells. RESULTS: PDGF receptors (PDGFR) and their ligands are frequently expressed
      in cervical cancer and the majority exhibited a combination of family members co
      expression. A number of intronic and exonic variations but no known mutations in
      the coding sequence of the PDGFRalpha gene were found in cancer cell lines and
      primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation
      that can be blocked by imatinib and that this tyrosine kinase inhibitor on its
      own inhibits cell growth. These effects were associated with the phosphorylation
      status of the receptor. CONCLUSION: The PDGFR system may have a role in the
      pathogenesis of cervical cancer as their members are frequently expressed in this
      tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist
      imatinib.

PMID- 17014710
TI  - Dispersal strategies of phytophagous insects at a local scale: adaptive potential
      of aphids in an agricultural environment.
AB  - BACKGROUND: The spread of agriculture greatly modified the selective pressures
      exerted by plants on phytophagous insects, by providing these insects with a high
      level resource, structured in time and space. The life history, behavioural and
      physiological traits of some insect species may have evolved in response to these
      changes, allowing them to crowd on crops and to become agricultural pests.
      Dispersal, which is one of these traits, is a key concept in evolutionary biology
      but has been over-simplified in most theoretical studies. We evaluated the impact
      of the local-scale dispersal strategy of phytophagous insects on their fitness,
      using an individual-based model to simulate population dynamics and dispersal
      between leaves and plants, by walking and flying, of the aphid Aphis gossypii, a
      major agricultural pest, in a melon field. We compared the optimal values for
      dispersal parameters in the model with the corresponding observed values in
      experimental trials. RESULTS: We show that the rates of walking and flying
      disperser production on leaves were the most important traits determining the
      fitness criteria, whereas dispersal distance and the clustering of flying
      dispersers on the target plant had no effect. We further show that the effect of
      dispersal parameters on aphid fitness depended strongly on plant characteristics.
      CONCLUSION: Parameters defining the dispersal strategies of aphids at a local
      scale are key components of the fitness of these insects and may thus be
      essential in the adaptation to agricultural environments that are structured in
      space and time. Moreover, the fact that the effect of dispersal parameters on
      aphid fitness depends strongly on plant characteristics suggests that traits
      defining aphid dispersal strategies may be a cornerstone of host-plant
      specialization.

PMID- 17014711
TI  - Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular
      carcinoma cells towards apoptosis induction.
AB  - BACKGROUND: Hepatocelluar carcinoma (HCC) is one of the most common cancers
      worldwide and a major cause of cancer-related mortality. HCC is highly resistant
      to currently available chemotherapeutic drugs. Defects in apoptosis signaling
      contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti
      apoptotic member of the Bcl-2 protein family which interferes with mitochondrial
      activation. In a previous study we have shown that Mcl-1 is highly expressed in
      tissues of human HCC. In this study, we manipulated expression of the Mcl-1
      protein in HCC cells by RNA interference and analyzed its impact on apoptosis
      sensitivity of HCC cells in vitro. METHODS: RNA interference was performed by
      transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl
      1 expression was measured by quantitative real-time PCR and Western blot.
      Induction of apoptosis and caspase activity after treatment with chemotherapeutic
      drugs and different targeted therapies were measured by flow cytometry and
      fluorometric analysis, respectively. RESULTS: Here we demonstrate that Mcl-1
      expressing HCC cell lines show low sensitivity towards treatment with a panel of
      chemotherapeutic drugs. However, treatment with the anthracycline derivative
      epirubicin resulted in comparatively high apoptosis rates in HCC cells.
      Inhibition of the kinase PI3K significantly increased apoptosis induction by
      chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC
      cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic
      agents. Sensitization was accompanied by profound activation of caspase-3 and -9.
      In addition, Mcl-1 downregulation also increased apoptosis rates after treatment
      with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and
      VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to
      Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis
      sensitivity towards combined treatment modalities: Mcl-1 knockdown significantly
      augmented apoptosis sensitivity of HCC cells towards chemotherapy combined with
      PI3K inhibition. CONCLUSION: Our data suggest that specific downregulation of Mcl
      1 by RNA interference is a promising approach to sensitize HCC cells towards
      chemotherapy and molecularly targeted therapies.

PMID- 17014712
TI  - High-resolution analysis of HLA class I alterations in colorectal cancer.
AB  - BACKGROUND: Previous studies indicate that alterations in Human Leukocyte Antigen
      (HLA) class I expression are frequent in colorectal tumors. This would suggest
      serious limitations for immunotherapy-based strategies involving T-cell
      recognition. Distinct patterns of HLA surface expression might conceal different
      immune escape mechanisms employed by the tumors and are worth further study.
      METHOD: We applied four-color multiparameter flow cytometry (FCM), using a large
      panel of alloantigen-specific anti-HLA-A and -B monoclonal antibodies, to study
      membranous expression of individual HLA alleles in freshly isolated colorectal
      cancer cell suspensions from 21 patients. RESULTS: Alterations in HLA class I
      phenotype were observed in 8 (38%) of the 21 tumors and comprised loss of a
      single A or B alleles in 4 cases, and loss of all four A and B alleles in the
      other 4 cases. Seven of these 8 tumors were located on the right side of the
      colon, and those showing loss of both HLA-A and -B membranous expression were all
      of the MSI-H phenotype. CONCLUSION: FCM allows the discrimination of complex
      phenotypes related to the expression of HLA class I. The different patterns of
      HLA class I expression might underlie different tumor behavior and influence the
      success rate of immunotherapy.

PMID- 17014713
TI  - General practitioner practices in requesting laboratory tests for patients with
      gastroenteritis in the Netherlands, 2001-2002.
AB  - BACKGROUND: The objective of this study was to estimate the (selective)
      proportion of patients consulting their GP for an episode of gastroenteritis for
      whom laboratory tests were requested. In addition adherence of GPs to the
      guidelines for diagnostic test regime was ascertained. METHODS: Data were
      collected from a GP network in the Netherlands. Information was also collected on
      the reason for requesting the test, test specifications, and test results.
      RESULTS: For 12% of the GP patients with gastroenteritis, a stool sample was
      requested and tested for enteric pathogens. In most patients, the duration,
      followed by severity of complaints or a visit to a specific, high-risk country
      were reported as reasons to request laboratory diagnostics. Tests were requested
      most often in summer months and in February. Campylobacter (requested for 87% of
      the tests), Salmonella (84%), Shigella (78%) and Yersinia (56%) were most
      frequently included in the stool tests. Campylobacter was detected most often in
      patients. CONCLUSION: Test requests did not always comply with existing knowledge
      of the etiology of gastroenteritis in GP patients and were not always consistent
      with the Dutch GP guidelines. Therefore, the data of this study can be used to
      develop educational approaches for GP's as well as for revision of the
      guidelines.

PMID- 17014714
TI  - Study protocol: delayed intervention randomised controlled trial within the
      Medical Research Council (MRC) Framework to assess the effectiveness of a new
      palliative care service.
AB  - BACKGROUND: Palliative care has been proposed to help meet the needs of patients
      who suffer progressive non-cancer conditions but there have been few evaluations
      of service development initiatives. We report here a novel protocol for the
      evaluation of a new palliative care service in this context. METHODS/DESIGN:
      Using the MRC Framework for the Evaluation of Complex Interventions we modelled a
      new palliative care and neurology service for patients severely affected by
      Multiple Sclerosis (MS). We conducted qualitative interviews with patients,
      families and staff, plus a literature review to model and pilot the service. Then
      we designed a delayed intervention randomised controlled trial to test its
      effectiveness as part of phase II of the MRC framework. Inclusion criteria for
      the trial were patients identified by referring clinicians as having unresolved
      symptoms or psychological concerns. Referrers were advised to use a score of
      greater than 8 on the Expanded Disability Scale was a benchmark. Consenting
      patients newly referred to the new service were randomised to either receive the
      palliative care service immediately (fast-track) or after a 12-week wait
      (standard best practice). Face to face interviews were conducted at baseline
      (before intervention), and at 4-6, 10-12 (before intervention for the standard
      practice group), 16-18 and 22-24 weeks with patients and their carers using
      standard questionnaires to assess symptoms, palliative care outcomes, function,
      service use and open comments. Ethics committee approval was granted separately
      for the qualitative phase and then for the trial. DISCUSSION: We publish the
      protocol trial here, to allow methods to be reviewed in advance of publication of
      the results. The MRC Framework for the Evaluation of Complex Interventions was
      helpful in both the design of the service, methods for evaluation in convincing
      staff and the ethics committee to accept the trial. The research will provide
      valuable information on the effects of palliative care among non-cancer patients
      and a method to evaluate palliative care in this context.

PMID- 17014715
TI  - Detection of prokaryotic promoters from the genomic distribution of
      hexanucleotide pairs.
AB  - BACKGROUND: In bacteria, sigma factors and other transcriptional regulatory
      proteins recognize DNA patterns upstream of their target genes and interact with
      RNA polymerase to control transcription. As a consequence of evolution, DNA
      sequences recognized by transcription factors are thought to be enriched in
      intergenic regions (IRs) and depleted from coding regions of prokaryotic genomes.
      RESULTS: In this work, we report that genomic distribution of transcription
      factors binding sites is biased towards IRs, and that this bias is conserved
      amongst bacterial species. We further take advantage of this observation to
      develop an algorithm that can efficiently identify promoter boxes by a
      distribution-dependent approach rather than a direct sequence comparison
      approach. This strategy, which can easily be combined with other methodologies,
      allowed the identification of promoter sequences in ten species and can be used
      with any annotated bacterial genome, with results that rival with current
      methodologies. Experimental validations of predicted promoters also support our
      approach. CONCLUSION: Considering that complete genomic sequences of over 1000
      bacteria will soon be available and that little transcriptional information is
      available for most of them, our algorithm constitutes a promising tool for the
      prediction of promoter sequences. Importantly, our methodology could also be
      adapted to identify DNA sequences recognized by other regulatory proteins.

PMID- 17014716
TI  - Effects of prostratin on Cyclin T1/P-TEFb function and the gene expression
      profile in primary resting CD4+ T cells.
AB  - BACKGROUND: The latent reservoir of human immunodeficiency virus type 1 (HIV-1)
      in resting CD4+ T cells is a major obstacle to the clearance of infection by
      highly active antiretroviral therapy (HAART). Recent studies have focused on
      searches for adjuvant therapies to activate this reservoir under conditions of
      HAART. Prostratin, a non tumor-promoting phorbol ester, is a candidate for such a
      strategy. Prostratin has been shown to reactivate latent HIV-1 and Tat-mediated
      transactivation may play an important role in this process. We examined resting
      CD4+ T cells from healthy donors to determine if prostratin induces Cyclin T1/P
      TEFb, a cellular kinase composed of Cyclin T1 and Cyclin-dependent kinase-9
      (CDK9) that mediates Tat function. We also examined effects of prostratin on
      Cyclin T2a, an alternative regulatory subunit for CDK9, and 7SK snRNA and the
      HEXIM1 protein, two factors that associate with P-TEFb and repress its kinase
      activity. RESULTS: Prostratin up-regulated Cyclin T1 protein expression, modestly
      induced CDK9 protein expression, and did not affect Cyclin T2a protein
      expression. Although the kinase activity of CDK9 in vitro was up-regulated by
      prostratin, we observed a large increase in the association of 7SK snRNA and the
      HEXIM1 protein with CDK9. Using HIV-1 reporter viruses with and without a
      functional Tat protein, we found that prostratin stimulation of HIV-1 gene
      expression appears to require a functional Tat protein. Microarray analyses were
      performed and several genes related to HIV biology, including APOBEC3B, DEFA1,
      and S100 calcium-binding protein genes, were found to be regulated by prostratin.
      CONCLUSION: Prostratin induces Cyclin T1 expression and P-TEFb function and this
      is likely to be involved in prostratin reactivation of latent HIV-1 proviruses.
      The large increase in association of 7SK and HEXIM1 with P-TEFb following
      prostratin treatment may reflect a requirement in CD4+ T cells for a precise
      balance between active and catalytically inactive P-TEFb. Additionally, genes
      regulated by prostratin were identified that have the potential to regulate HIV-1
      replication both positively and negatively.

PMID- 17014717
TI  - Short G-rich oligonucleotides as a potential therapeutic for Huntington's
      Disease.
AB  - BACKGROUND: Huntington's Disease (HD) is an inherited autosomal dominant genetic
      disorder in which neuronal tissue degenerates. The pathogenesis of the disease
      appears to center on the development of protein aggregates that arise initially
      from the misfolding of the mutant HD protein. Mutant huntingtin (Htt) is produced
      by HD genes that contain an increased number of glutamine codons within the first
      exon and this expansion leads to the production of a protein that misfolds.
      Recent studies suggest that mutant Htt can nucleate protein aggregation and
      interfere with a multitude of normal cellular functions. RESULTS: As such,
      efforts to find a therapy for HD have focused on agents that disrupt or block the
      mutant Htt aggregation pathway. Here, we report that short guanosine monotonic
      oligonucleotides capable of adopting a G-quartet structure, are effective
      inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an
      initial screen, we identified a 20-mer, all G-oligonucleotide (HDG) as an active
      molecule. Subsequent testing in a cell-based assay revealed that HDG was an
      effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt
      fragment and green fluorescent protein (eGFP). Taken together, our results
      suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet
      conformation is an effective inhibitor of aggregation. This oligonucleotide can
      also enable cell survival in PC12 cells overexpressing a mutant Htt fragment
      fusion gene. CONCLUSION: Single-stranded DNA oligonucleotides capable of forming
      stable G-quartets can inhibit aggregation of the mutant Htt fragment protein.
      This activity maybe an important part of the pathogenecity of Huntington's
      Disease. Our results reveal a new class of agents that could be developed as a
      therapeutic approach for Huntington's Disease.

PMID- 17014719
TI  - PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53.
AB  - PUMA (p53-upregulated modulator of apoptosis) is a pro-apoptotic gene that can
      induce rapid cell death through a p53-dependent mechanism. However, the efficacy
      of PUMA gene therapy to induce synovial apoptosis in rheumatoid arthritis might
      have limited efficacy if p53 expression or function is deficient. To evaluate
      this issue, studies were performed to determine whether p53 is required for PUMA
      mediated apoptosis in fibroblast-like synoviocytes (FLS). p53 protein was
      depleted or inhibited in human FLS by using p53 siRNA or a dominant-negative p53
      protein. Wild-type and p53-/- murine FLS were also examined to evaluate whether
      p53 is required. p53-deficient or control FLS were transfected with PUMA cDNA or
      empty vector. p53 and p21 expression were then determined by Western blot
      analysis. Apoptosis was assayed by ELISA to measure histone release and caspase-3
      activation, or by trypan blue dye exclusion to measure cell viability. Initial
      studies showed that p53 siRNA decreased p53 expression by more than 98% in human
      FLS. Loss of p53 increased the growth rate of cells and suppressed p21
      expression. However, PUMA still induced apoptosis in control and p53-deficient
      FLS after PUMA cDNA transfection. Similar results were observed in p53-/- murine
      FLS or in human FLS transfected with a dominant-negative mutant p53 gene. These
      data suggest that PUMA-induced apoptosis in FLS does not require p53. Therefore,
      approaches to gene therapy that involve increasing PUMA expression could be an
      effective inducer of synoviocyte cell death in rheumatoid arthritis regardless of
      the p53 status in the synovium.

PMID- 17014720
TI  - PubFocus: semantic MEDLINE/PubMed citations analytics through integration of
      controlled biomedical dictionaries and ranking algorithm.
AB  - BACKGROUND: Understanding research activity within any given biomedical field is
      important. Search outputs generated by MEDLINE/PubMed are not well classified and
      require lengthy manual citation analysis. Automation of citation analytics can be
      very useful and timesaving for both novices and experts. RESULTS: PubFocus web
      server automates analysis of MEDLINE/PubMed search queries by enriching them with
      two widely used human factor-based bibliometric indicators of publication
      quality: journal impact factor and volume of forward references. In addition to
      providing basic volumetric statistics, PubFocus also prioritizes citations and
      evaluates authors' impact on the field of search. PubFocus also analyses presence
      and occurrence of biomedical key terms within citations by utilizing controlled
      vocabularies. CONCLUSION: We have developed citations' prioritisation algorithm
      based on journal impact factor, forward referencing volume, referencing dynamics,
      and author's contribution level. It can be applied either to the primary set of
      PubMed search results or to the subsets of these results identified through key
      terms from controlled biomedical vocabularies and ontologies. NCI (National
      Cancer Institute) thesaurus and MGD (Mouse Genome Database) mammalian gene
      orthology have been implemented for key terms analytics. PubFocus provides a
      scalable platform for the integration of multiple available ontology databases.
      PubFocus analytics can be adapted for input sources of biomedical citations other
      than PubMed.

PMID- 17014718
TI  - Intrinsic and selected resistance to antibiotics binding the ribosome: analyses
      of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic
      implications.
AB  - BACKGROUND: Brucella spp. are highly similar, having identical 16S RNA. However,
      they have important phenotypic differences such as differential susceptibility to
      antibiotics binding the ribosome. Neither the differential susceptibility nor its
      basis has been rigorously studied. Differences found among other conserved
      ribosomal loci could further define the relationships among the classical
      Brucella spp. RESULTS: Minimum inhibitory concentration (MIC) values of Brucella
      reference strains and three marine isolates to antibiotics binding the ribosome
      ranged from 0.032 to >256 microg/ml for the macrolides erythromycin,
      clarithromycin, and azithromycin and 2 to >256 microg/ml for the lincosamide,
      clindamycin. Though sequence polymorphisms were identified among ribosome
      associated loci 23S rrn, rplV, tuf-1 and tuf-2 but not rplD, they did not
      correlate with antibiotic resistance phenotypes. When spontaneous erythromycin
      resistant (eryR) mutants were examined, mutation of the peptidyl transferase
      center (A2058G Ec) correlated with increased resistance to both erythromycin and
      clindamycin. Brucella efflux was examined as an alternative antibiotic resistance
      mechanism by use of the inhibitor L-phenylalanine-L-arginine beta-naphthylamide
      (PAbetaN). Erythromycin MIC values of reference and all eryR strains, except the
      B. suis eryR mutants, were lowered variably by PAbetaN. A phylogenetic tree based
      on concatenated ribosomal associated loci supported separate evolutionary paths
      for B. abortus, B. melitensis, and B. suis/B. canis, clustering marine Brucella
      and B. neotomae with B. melitensis. Though Brucella ovis was clustered with B.
      abortus, the bootstrap value was low. CONCLUSION: Polymorphisms among ribosomal
      loci from the reference Brucella do not correlate with their highly differential
      susceptibility to erythromycin. Efflux plays an important role in Brucella
      sensitivity to erythromycin. Polymorphisms identified among ribosome associated
      loci construct a robust phylogenetic tree supporting classical Brucella spp.
      designations.

PMID- 17014721
TI  - Distribution of hepatitis C virus genotypes in patients infected by different
      sources and its correlation with clinical and virological parameters: a
      preliminary study.
AB  - BACKGROUND: Information about genotypes and associated risk factors in hepatitis
      C virus (HCV) infected patients in Iran is limited. The aim of this study was to
      identify the HCV genotypes and associated risk factors in a group of HCV infected
      patients from Iran. RESULTS: Genotyping analysis was performed in 156 patients
      with positive anti-HCV and HCV-RNA. Patients were questioned concerning
      documented risk factors. Genotypes 1 and 3 were found in 87 (55.8%) and 45
      (28.8%) patients, respectively. The most frequent HCV subtype was 1a (37.8),
      followed by 3a (28.9%) and 1b (16.7%). There was no statistically significant
      difference between the risk factors analyzed and the acquisition of HCV
      infection. We further found that 18 (40%) and 17 (37.8%) patients that were
      intravenous drug users (IVDU) had genotype 1a and 3a respectively. CONCLUSION:
      Genotypes 3a and 1a in Iran are less prevalent in IVDU than in Europe and USA,
      but there is a high similarity between the pattern of genotype in IVDU in both
      Europe and United States, and Iran. However, in this case it can not be due to
      people migration among countries since history of travel abroad existed only in 6
      cases (13.3%).

PMID- 17014722
TI  - A major genetic component of BSE susceptibility.
AB  - BACKGROUND: Coding variants of the prion protein gene (PRNP) have been shown to
      be major determinants for the susceptibility to transmitted prion diseases in
      humans, mice and sheep. However, to date, the effects of polymorphisms in the
      coding and regulatory regions of bovine PRNP on bovine spongiform encephalopathy
      (BSE) susceptibility have been considered marginal or non-existent. Here we
      analysed two insertion/deletion (indel) polymorphisms in the regulatory region of
      bovine PRNP in BSE affected animals and controls of four independent cattle
      populations from UK and Germany. RESULTS: In the present report, we show that two
      previously reported 23- and 12-bp insertion/deletion (indel) polymorphisms in the
      regulatory region of bovine PRNP are strongly associated with BSE incidence in
      cattle. Genotyping of BSE-affected and control animals of UK Holstein, German
      Holstein, German Brown and German Fleckvieh breeds revealed a significant
      overrepresentation of the deletion alleles at both polymorphic sites in diseased
      animals (P = 2.01 x 10(-3) and P = 8.66 x 10(-5), respectively). The main effect
      on susceptibility is associated with the 12-bp indel polymorphism. Compared with
      non-carriers, heterozygous and homozygous carriers of the 12-bp deletion allele
      possess relatively higher risks of having BSE, ranging from 1.32 to 4.01 and 1.74
      to 3.65 in the different breeds. These values correspond to population
      attributable risks ranging from 35% to 53%. CONCLUSION: Our results demonstrate a
      substantial genetic PRNP associated component for BSE susceptibility in cattle.
      Although the BSE risk conferred by the deletion allele of the 12-bp indel in the
      regulatory region of PRNP is substantial, the main risk factor for BSE in cattle
      is environmental, i.e. exposure to feedstuffs contaminated with the infectious
      agent.

PMID- 17014723
TI  - The four serotypes of dengue recognize the same putative receptors in Aedes
      aegypti midgut and Ae. albopictus cells.
AB  - BACKGROUND: Dengue viruses (DENV) attach to the host cell surface and
      subsequently enter the cell by receptor-mediated endocytosis. Several primary and
      low affinity co-receptors for this flavivirus have been identified. However, the
      presence of these binding molecules on the cell surface does not necessarily
      render the cell susceptible to infection. Determination of which of them serve as
      bona fide receptors for this virus in the vector may be relevant to treating DENV
      infection and in designing control strategies. RESULTS: (1) Overlay protein
      binding assay showed two proteins with molecular masses of 80 and 67 kDa (R80 and
      R67). (2) Specific antibodies against these two proteins inhibited cell binding
      and infection. (3) Both proteins were bound by all four serotypes of dengue
      virus. (4) R80 and R67 were purified by affinity chromatography from Ae. aegypti
      mosquito midguts and from Ae albopictus C6/36 cells. (5) In addition, a protein
      with molecular mass of 57 kDa was purified by affinity chromatography from the
      midgut extracts. (6) R80 and R67 from radiolabeled surface membrane proteins of
      C6/36 cells were immunoprecipitated by antibodies against Ae. aegypti midgut.
      CONCLUSION: Our results strongly suggest that R67 and R80 are receptors for the
      four serotypes of dengue virus in the midgut cells of Ae. aegypti and in C6/36
      Ae. albopictus cells.

PMID- 17014724
TI  - The impact of altitude on early outcome following the Fontan operation.
AB  - BACKGROUND: The success of a Fontan circulation depends on several factors
      including low pulmonary vascular resistance. Pulmonary vascular resistance rises
      in response to hypoxia. Hypoxia is associated with altitude. Therefore, we
      wondered whether altitude is a risk factor for early failure after the Fontan
      operation. The aim was to test this hypothesis. METHODS: Data were obtained from
      all published series of 'total cavopulmonary' Fontan operations since 1990. The
      early failure rate from each series and the altitude of the respective cities
      were recorded. Early failure was defined as death, takedown of Fontan, or
      transplantation during the same hospital admission. The association between
      altitude and failure rate was investigated by rank correlation and logistic
      regression. RESULTS: 24 series were identified from centres situated at altitudes
      ranging from sea level to 520 metres. The plot of failure rate versus altitude
      suggests that failure rate increases with altitude. Logistic regression did not
      fit the data adequately. This was possibly due to the influence of unmeasured and
      unknown factors affecting the results, as well as the fact that centres were not
      randomly chosen but were self-selected by virtue of publishing their results.
      However, Spearman's rank correlation was 0.74 (p = 0.001). CONCLUSION: The early
      outcome of the Fontan circulation appears to be adversely affected by altitude.

PMID- 17014725
TI  - Homeless drug users' awareness and risk perception of peer "take home naloxone"
      use--a qualitative study.
AB  - BACKGROUND: Peer use of take home naloxone has the potential to reduce drug
      related deaths. There appears to be a paucity of research amongst homeless drug
      users on the topic. This study explores the acceptability and potential risk of
      peer use of naloxone amongst homeless drug users. From the findings the most
      feasible model for future treatment provision is suggested. METHODS: In depth
      face-to-face interviews conducted in one primary care centre and two voluntary
      organisation centres providing services to homeless drug users in a large UK
      cosmopolitan city. Interviews recorded, transcribed and analysed thematically by
      framework techniques. RESULTS: Homeless people recognise signs of a heroin
      overdose and many are prepared to take responsibility to give naloxone, providing
      prior training and support is provided. Previous reports of the theoretical
      potential for abuse and malicious use may have been overplayed. CONCLUSION: There
      is insufficient evidence to recommend providing "over the counter" take home
      naloxone" to UK homeless injecting drug users. However a programme of peer use of
      take home naloxone amongst homeless drug users could be feasible providing prior
      training is provided. Peer education within a health promotion framework will
      optimise success as current professionally led health promotion initiatives are
      failing to have a positive impact amongst homeless drug users.

PMID- 17014728
TI  - Individual freedom versus collective responsibility: too many rights make a
      wrong?
AB  - : Individuals might reasonably expect the freedom to make their own decisions
      regarding their health. However, what happens when an individual's wishes
      conflict with what is in that individual's best interests? How far should an
      individual's rights be restricted for his or her own benefit? Similarly, what
      limitations should be placed on an individual's behaviour when that person's
      wishes go against what is good for the population in general? Here we discuss the
      issues that can arise when the rights of individuals conflict with individual and
      population benefits in relation to infectious diseases.

PMID- 17014726
TI  - Generation Scotland: the Scottish Family Health Study; a new resource for
      researching genes and heritability.
AB  - BACKGROUND: Generation Scotland: the Scottish Family Health Study aims to
      identify genetic variants accounting for variation in levels of quantitative
      traits underlying the major common complex diseases (such as cardiovascular
      disease, cognitive decline, mental illness) in Scotland. METHODS/DESIGN:
      Generation Scotland will recruit a family-based cohort of up to 50,000
      individuals (comprising siblings and parent-offspring groups) across Scotland. It
      will be a six-year programme, beginning in Glasgow and Tayside in the first two
      years (Phase 1) before extending to other parts of Scotland in the remaining four
      years (Phase 2). In Phase 1, individuals aged between 35 and 55 years, living in
      the East and West of Scotland will be invited to participate, along with at least
      one (and preferably more) siblings and any other first degree relatives aged 18
      or over. The total initial sample size will be 15,000 and it is planned that this
      will increase to 50,000 in Phase 2. All participants will be asked to contribute
      blood samples from which DNA will be extracted and stored for future
      investigation. The information from the DNA, along with answers to a life-style
      and medical history questionnaire, clinical and biochemical measurements taken at
      the time of donation, and subsequent health developments over the life course
      (traced through electronic health records) will be stored and used for research
      purposes. In addition, a detailed public consultation process will begin that
      will allow respondents' views to shape and develop the study. This is an
      important aspect to the research, and forms the continuation of a long-term
      parallel engagement process. DISCUSSION: As well as gene identification, the
      family-based study design will allow measurement of the heritability and familial
      aggregation of relevant quantitative traits, and the study of how genetic effects
      may vary by parent-of-origin. Long-term potential outcomes of this research
      include the targeting of disease prevention and treatment, and the development of
      screening tools based on the new genetic information. This study approach is
      complementary to other population-based genetic epidemiology studies, such as UK
      Biobank, which are established primarily to characterise genes and genetic risk
      in the population.

PMID- 17014727
TI  - A novel assay for monitoring internalization of nanocarrier coupled antibodies.
AB  - BACKGROUND: Discovery of tumor-selective antibodies or antibody fragments is a
      promising approach for delivering therapeutic agents to antigen over-expressing
      cancers. Therefore it is important to develop methods for the identification of
      target- and function specific antibodies for effective drug delivery. Here we
      describe a highly selective and sensitive method for characterizing the
      internalizing potential of multivalently displayed antibodies or ligands
      conjugated to liposomes into tumor cells. The assay requires minute amounts of
      histidine-tagged ligand and relies on the non-covalent coupling of these
      antibodies to fluorescent liposomes containing a metal ion-chelating lipid.
      Following incubation of cells with antibody-conjugated liposomes, surface bound
      liposomes are gently removed and the remaining internalized liposomes are
      quantitated based on fluorescence in a high throughput manner. We have termed
      this methodology "Chelated Ligand Internalization Assay", or CLIA. RESULTS: The
      specificity of the assay was demonstrated with different antibodies to the ErbB-2
      and EGF receptors. Antibody-uptake correlated with receptor expression levels in
      tumor cell lines with a range of receptor expression. Furthermore, Ni-NTA
      liposomes containing doxorubicin were used to screen for the ability of
      antibodies to confer target-specific cytotoxicity. Using an anti-ErbB2 single
      chain Fv (scFv) (F5) antibody, cytotoxicity could be conferred to ErbB2
      overexpressing cells; however, a poly(ethylene glycol)-linked lipid (DSPE-PEG-NTA
      Ni) was necessary to allow for efficient loading of the drug and to reduce
      nonspecific drug leakage during the course of the assay. CONCLUSION: The CLIA
      method we describe here represents a rapid, sensitive and robust assay for the
      identification and characterization of tumor-specific antibodies capable of high
      drug-delivery efficiency when conjugated to liposomal nanocarriers.

PMID- 17014729
TI  - The vicinal difluoro motif: The synthesis and conformation of erythro- and threo-
      diastereoisomers of 1,2-difluorodiphenylethanes, 2,3-difluorosuccinic acids and
      their derivatives.
AB  - BACKGROUND: It is well established that vicinal fluorines (RCHF-CHFR) prefer to
      adopt a gauche rather than an anti conformation when placed along aliphatic
      chains. This has been particularly recognised for 1,2-difluoroethane and extends
      to 2,3-difluorobutane and longer alkyl chains. It follows in these latter cases
      that if erythro and threo vicinal difluorinated stereoisomers are compared, they
      will adopt different overall conformations if the fluorines prefer to be gauche
      in each case. This concept is explored in this paper with erythro- and threo-
      diastereoisomers of 2,3-difluorosuccinates. RESULTS: A synthetic route to 2,3
      difluorosuccinates has been developed through erythro- and threo- 1,2-difluoro
      1,2-diphenylethane which involved the oxidation of the aryl rings to generate the
      corresponding 2,3-difluorosuccinic acids. Ester and amide derivatives of the
      erythro- and threo- 2,3-difluorosuccinic acids were then prepared. The solid and
      solution state conformation of these compounds was assessed by X-ray
      crystallography and NMR. Ab initio calculations were also carried out to model
      the conformation of erythro- and threo- 1,2-difluoro-1,2-diphenylethane as these
      differed from the 2,3-difluorosuccinates. CONCLUSION: In general the overall
      chain conformations of the 2,3-difluorosuccinates diastereoisomers were found to
      be influenced by the fluorine gauche effect. The study highlights the prospects
      of utilising the vicinal difluorine motif (RCHF-CHFR) as a tool for influencing
      the conformation of performance organic molecules and particularly tuning
      conformation by selecting specific diastereoisomers (erythro or threo).

PMID- 17014730
TI  - Clock mutation affects circadian regulation of circulating blood cells.
AB  - BACKGROUND: Although the number of circulating immune cells is subject to high
      amplitude circadian rhythms, the underlying mechanisms are not fully understood.
      METHODS: To determine whether intact CLOCK protein is required for the circadian
      changes in peripheral blood cells, we examined circulating white (WBC) and red
      (RBC) blood cells in homozygous Clock mutant mice. RESULTS: Daytime increases in
      total WBC and lymphocytes were suppressed and slightly phase-delayed along with
      plasma corticosterone levels in Clock mutant mice. The peak RBC rhythm was
      significantly reduced and phase-advanced in the Clock mutants. Anatomical
      examination revealed hemoglobin-rich, swollen red spleens in Clock mutant mice,
      suggesting RBC accumulation. CONCLUSION: Our results suggest that endogenous
      clock-regulated circadian corticosterone secretion from the adrenal gland is
      involved in the effect of a Clock mutation on daily profiles of circulating WBC.
      However, intact CLOCK seems unnecessary for generating the rhythm of
      corticosterone secretion in mice. Our results also suggest that CLOCK is involved
      in discharge of RBC from the spleen.

PMID- 17014731
TI  - Nordic walking and chronic low back pain: design of a randomized clinical trial.
AB  - BACKGROUND: Low Back Pain is a major public health problem all over the western
      world. Active approaches including exercise in the treatment of low back pain
      results in better outcomes for patients, but it is not known exactly which types
      of back exercises are most beneficial or whether general physical activity
      provide similar benefits. Nordic Walking is a popular and fast growing type of
      exercise in Northern Europe. Initial studies have demonstrated that persons
      performing Nordic Walking are able to exercise longer and harder compared to
      normal walking thereby increasing their cardiovascular metabolism. Until now no
      studies have been performed to investigate whether Nordic Walking has beneficial
      effects in relation to low back pain. The primary aim of this study is to
      investigate whether supervised Nordic Walking can reduce pain and improve
      function in a population of chronic low back pain patients when compared to
      unsupervised Nordic Walking and advice to stay active. In addition we investigate
      whether there is an increase in the cardiovascular metabolism in persons
      performing supervised Nordic Walking compared to persons who are advised to stay
      active. Finally, we investigate whether there is a difference in compliance
      between persons receiving supervised Nordic Walking and persons doing
      unsupervised Nordic Walking. METHODS: One hundred and fifty patients with low
      back pain for at least eight weeks and referred to a specialized secondary sector
      outpatient back pain clinic are included in the study. After completion of the
      standard back centre treatment patients are randomized into one of three groups:
      A) Nordic Walking twice a week for eight weeks under supervision of a specially
      trained instructor; B) Unsupervised Nordic Walking for eight weeks after one
      training session with an instructor; C) A one hour motivational talk including
      advice to stay active. Outcome measures are pain, function, overall health,
      cardiovascular ability and activity level. RESULTS: No results available at this
      point. DISCUSSION: This study will investigate the effect of Nordic Walking on
      pain and function in a population of people with chronic LBP.

PMID- 17014732
TI  - Migration and health: fact, fiction, art, politics.
AB  - The recent Immigration Bill debate in the United States Congress has again re
      ignited the polemic regarding immigration policy. In this essay, I argue that
      disputes surrounding the legality of migrant workers highlight chronic,
      underlying problems related to factors that drive migration. The public health
      field, although concerned primarily with addressing the health needs of migrant
      populations, cannot remain disengaged from the wider debates about migration. The
      health needs of migrants, although in themselves important, are merely symptoms
      of deeper structural process that are intrinsically linked to equity and human
      rights, and simply focusing on health issues will be insufficient to address
      these societal pathologies.

PMID- 17014733
TI  - A three-dimensional multivariate image processing technique for the analysis of
      FTIR spectroscopic images of multiple tissue sections.
AB  - BACKGROUND: Three-dimensional (3D) multivariate Fourier Transform Infrared (FTIR)
      image maps of tissue sections are presented. A villoglandular adenocarcinoma from
      a cervical biopsy with a number of interesting anatomical features was used as a
      model system to demonstrate the efficacy of the technique. METHODS: Four FTIR
      images recorded using a focal plane array detector of adjacent tissue sections
      were stitched together using a MATLAB routine and placed in a single data matrix
      for multivariate analysis using Cytospec. Unsupervised Hierarchical Cluster
      Analysis (UHCA) was performed simultaneously on all 4 sections and 4 clusters
      plotted. The four UHCA maps were then stacked together and interpolated with a
      box function using SCIRun software. RESULTS: The resultant 3D-images can be
      rotated in three-dimensions, sliced and made semi-transparent to view the
      internal structure of the tissue block. A number of anatomical and
      histopathological features including connective tissue, red blood cells,
      inflammatory exudate and glandular cells could be identified in the cluster maps
      and correlated with Hematoxylin & Eosin stained sections. The mean extracted
      spectra from individual clusters provide macromolecular information on tissue
      components. CONCLUSION: 3D-multivariate imaging provides a new avenue to study
      the shape and penetration of important anatomical and histopathological features
      based on the underlying macromolecular chemistry and therefore has clear
      potential in biology and medicine.

PMID- 17014734
TI  - Differential expression of WNT4 in testicular and ovarian development in a
      marsupial.
AB  - BACKGROUND: WNT4 is a key regulator of gonadal differentiation in humans and
      mice, playing a pivotal role in early embryogenesis. Using a marsupial, the
      tammar wallaby, in which most gonadal differentiation occurs after birth whilst
      the young is in the pouch, we show by quantitative PCR during early testicular
      and ovarian development that WNT4 is differentially expressed in gonads. RESULTS:
      Before birth, WNT4 mRNA expression was similar in indifferent gonads of both
      sexes. After birth, in females WNT4 mRNA dramatically increased during ovarian
      differentiation, reaching a peak by day 9-13 post partum (pp) when the ovarian
      cortex and medulla are first distinguishable. WNT4 protein was localised in the
      ovarian cortex and at the medullary boundary. WNT4 mRNA then steadily decreased
      to day 49, by which time all the female germ cells have entered meiotic arrest.
      In males, WNT4 mRNA was down-regulated in testes immediately after birth,
      coincident with the time that seminiferous cords normally form, and rose
      gradually after day 8. By day 49, when testicular androgen production normally
      declines, WNT4 protein was restricted to the Leydig cells. CONCLUSION: This is
      the first localisation of WNT4 protein in developing gonads and is consistent
      with a role for WNT4 in steroidogenesis. Our data provide strong support for the
      suggestion that WNT4 not only functions as an anti-testis gene during early
      development, but is also necessary for later ovarian and testicular function.

PMID- 17014735
TI  - Predicting residue-wise contact orders in proteins by support vector regression.
AB  - BACKGROUND: The residue-wise contact order (RWCO) describes the sequence
      separations between the residues of interest and its contacting residues in a
      protein sequence. It is a new kind of one-dimensional protein structure that
      represents the extent of long-range contacts and is considered as a
      generalization of contact order. Together with secondary structure, accessible
      surface area, the B factor, and contact number, RWCO provides comprehensive and
      indispensable important information to reconstructing the protein three
      dimensional structure from a set of one-dimensional structural properties.
      Accurately predicting RWCO values could have many important applications in
      protein three-dimensional structure prediction and protein folding rate
      prediction, and give deep insights into protein sequence-structure relationships.
      RESULTS: We developed a novel approach to predict residue-wise contact order
      values in proteins based on support vector regression (SVR), starting from
      primary amino acid sequences. We explored seven different sequence encoding
      schemes to examine their effects on the prediction performance, including local
      sequence in the form of PSI-BLAST profiles, local sequence plus amino acid
      composition, local sequence plus molecular weight, local sequence plus secondary
      structure predicted by PSIPRED, local sequence plus molecular weight and amino
      acid composition, local sequence plus molecular weight and predicted secondary
      structure, and local sequence plus molecular weight, amino acid composition and
      predicted secondary structure. When using local sequences with multiple sequence
      alignments in the form of PSI-BLAST profiles, we could predict the RWCO
      distribution with a Pearson correlation coefficient (CC) between the predicted
      and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82,
      based on a well-defined dataset with 680 protein sequences. Moreover, by
      incorporating global features such as molecular weight and amino acid composition
      we could further improve the prediction performance with the CC to 0.57 and an
      RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED
      was found to significantly improve the prediction performance and could yield the
      best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at
      least comparable performance compared with the other existing methods.
      CONCLUSION: The SVR method shows a prediction performance competitive with or at
      least comparable to the previously developed linear regression-based methods for
      predicting RWCO values. In contrast to support vector classification (SVC), SVR
      is very good at estimating the raw value profiles of the samples. The successful
      application of the SVR approach in this study reinforces the fact that support
      vector regression is a powerful tool in extracting the protein sequence-structure
      relationship and in estimating the protein structural profiles from amino acid
      sequences.

PMID- 17014736
TI  - Loss of imprinting at the Dlk1-Gtl2 locus caused by insertional mutagenesis in
      the Gtl2 5' region.
AB  - BACKGROUND: The Dlk1 and Gtl2 genes define a region of mouse chromosome 12 that
      is subject to genomic imprinting, the parental allele-specific expression of a
      gene. Although imprinted genes play important roles in growth and development,
      the mechanisms by which imprinting is established and maintained are poorly
      understood. Differentially methylated regions (DMRs), which carry methylation on
      only one parental allele, are involved in imprinting control at many loci. The
      Dlk1-Gtl2 region contains three known DMRs, the Dlk1 DMR in the 3' region of
      Dlk1, the intergenic DMR 15 kb upstream of Gtl2, and the Gtl2 DMR at the Gtl2
      promoter. Three mouse models are analyzed here that provide new information about
      the regulation of Dlk1-Gtl2 imprinting. RESULTS: A previously existing
      insertional mutation (Gtl2lacZ), and a targeted deletion in which the Gtl2
      upstream region was replaced by a Neo cassette (Gtl2Delta5'Neo), display partial
      lethality and dwarfism upon paternal inheritance. Molecular characterization
      shows that both mutations cause loss of imprinting and changes in expression of
      the Dlk1, Gtl2 and Meg8/Rian genes. Dlk1 levels are decreased upon paternal
      inheritance of either mutation, suggesting Dlk1 may be causative for the
      lethality and dwarfism. Loss of imprinting on the paternal chromosome in both
      Gtl2lacZ and Gtl2Delta5'Neo mice is accompanied by the loss of paternal-specific
      Gtl2 DMR methylation, while maternal loss of imprinting suggests a previously
      unknown regulatory role for the maternal Gtl2 DMR. Unexpectedly, when the Neo
      gene is excised, Gtl2Delta5' animals are of normal size, imprinting is unchanged
      and the Gtl2 DMR is properly methylated. The exogenous DNA sequences integrated
      upstream of Gtl2 are therefore responsible for the growth and imprinting effects.
      CONCLUSION: These data provide further evidence for the coregulation of the
      imprinted Dlk1 and Gtl2 genes, and support a role for Dlk1 as an important
      neonatal growth factor. The ability of the Gtl2lacZ and Gtl2Delta5'Neo mutations
      to cause long-range changes in imprinting and gene expression suggest that
      regional imprinting regulatory elements may lie in proximity to the integration
      site.

PMID- 17014737
TI  - Co-activator p120 is increased by gonadotropins in the rat ovary and enhances
      progesterone receptor activity.
AB  - BACKGROUND: Ovarian follicular development is primarily dependent on pituitary
      gonadotropins. Identification of gonadotropin-inducible genes in the ovary is one
      of the effective approaches for the study of follicular development. In this
      study we identify rat homologue of p120, a nuclear transcription co-activator, as
      one of the FSH inducible genes in the rat granulosa cells. METHODS: A full-length
      cDNA encoding rat p120 was cloned, and expression of the gene in the ovary was
      examined by Northern blotting. Tissue localization of p120 was examined by in
      situ hybridization. Cellular functions of p120 were studied by co-transfection of
      rat p120 gene together with estrogen receptor (ER)-alpha, ER-beta, androgen
      receptor (AR), or progesterone receptor (PR) genes. RESULTS: A full-length cDNA
      encoding rat p120 was characterized as a protein with 957 amino acid residues.
      Rat p120 was expressed ubiquitously, but strongly in the ovary and the testis.
      Expression of p120 mRNA was also induced in vivo by PMSG or PMSG/hCG treatment.
      Strong expression of p120 mRNA was observed in the granulosa cells of pre
      ovulatory large antral follicles. Progesterone receptor was co-localized with
      p120 in the large antral follicles. Co-transfection experiments revealed that rat
      p120 activated AR, ER-alpha, ER-beta, and PR in the presence of their respective
      ligands. CONCLUSION: These observations suggest that rat p120 is strongly induced
      in the ovarian granulosa cells, and may work together with PR in the granulosa
      cells of ovulatory follicles to promote the ovulation process.

PMID- 17014740
TI  - Establishing interspecific mosaic genome lines between Drosophila ananassae and
      Drosophila pallidosa by means of parthenogenesis.
AB  - Strong sexual isolation exists between the closely related species Drosophila
      ananassae and D. pallidosa, but there is no obvious post-mating isolation; both
      sexes of the hybrids and their descendants appear to be completely viable and
      fertile. Strains exhibiting parthenogenesis have been derived from wild
      populations of both species. We intercrossed such strains and established iso
      female lines after the second generation of parthenogenesis. These lines are
      clones, carrying homozygous chromosomes that are interspecific recombinants. We
      established 266 such isogenic lines and determined their genetic constitution by
      using chromosomal and molecular markers. Strong pseudo-linkage was seen between
      loci on the left arm of chromosome 2 and on the right arm of chromosome 3; the
      frequency of inheriting the two chromosome regions from the same species was
      significantly larger than expected. One possible cause of pseudo-linkage is
      female meiotic bias, so that chromosomes of the same species origin tend to be
      distributed to the same gamete. But this possibility is ruled out; backcross
      analysis indicated that the two chromosome regions segregated independently in
      female hybrids. The remaining possibility is elimination of low-fitness flies
      carrying the two chromosome regions from different species. Thus, genetic
      incompatibility was detected in the species pair for which no hybrid breakdown
      had previously been indicated. The 'interspecific mosaic genome' lines reported
      here will be useful for future research to identify genes involved in speciation
      and phenotypic evolution.

PMID- 17014738
TI  - Evolution and origin of vomeronasal-type odorant receptor gene repertoire in
      fishes.
AB  - BACKGROUND: In teleost fishes that lack a vomeronasal organ, both main odorant
      receptors (ORs) and vomeronasal receptors family 2 (V2Rs) are expressed in the
      olfactory epithelium, and used for perception of water-soluble chemicals. In
      zebrafish, it is known that both ORs and V2Rs formed multigene families of about
      a hundred copies. Whereas the contribution of V2Rs in zebrafish to olfaction has
      been found to be substantially large, the composition and structure of the V2R
      gene family in other fishes are poorly known, compared with the OR gene family.
      RESULTS: To understand the evolutionary dynamics of V2R genes in fishes, V2R
      sequences in zebrafish, medaka, fugu, and spotted green pufferfish were
      identified from their draft genome sequences. There were remarkable differences
      in the number of intact V2R genes in different species. Most V2R genes in these
      fishes were tightly clustered in one or two specific chromosomal regions.
      Phylogenetic analysis revealed that the fish V2R family could be subdivided into
      16 subfamilies that had diverged before the separation of the four fishes. Genes
      in two subfamilies in zebrafish and another subfamily in medaka increased in
      their number independently, suggesting species-specific evolution in olfaction.
      Interestingly, the arrangements of V2R genes in the gene clusters were highly
      conserved among species in the subfamily level. A genomic region of tetrapods
      corresponding to the region in fishes that contains the V2R cluster was found to
      have no V2R gene in any species. CONCLUSION: Our results have indicated that the
      evolutionary dynamics of fish V2Rs are characterized by rapid gene turnover and
      lineage-specific phylogenetic clustering. In addition, the present phylogenetic
      and comparative genome analyses have shown that the fish V2Rs have expanded after
      the divergence between teleost and tetrapod lineages. The present identification
      of the entire V2R repertoire in fishes would provide useful foundation to the
      future functional and evolutionary studies of fish V2R gene family.

PMID- 17014739
TI  - Construction of a multiple fluorescence labelling system for use in co-invasion
      studies of Listeria monocytogenes.
AB  - BACKGROUND: Existing virulence models are often difficult to apply for
      quantitative comparison of invasion potentials of Listeria monocytogenes. Well-to
      well variation between cell-line based in vitro assays is practically
      unavoidable, and variation between individual animals is the cause of large
      deviations in the observed capacity for infection when animal models are used.
      One way to circumvent this problem is to carry out virulence studies as
      competition assays between 2 or more strains. This, however, requires invasion
      neutral markers that enable easy discrimination between the different strains.
      RESULTS: A fluorescent marker system, allowing visualization and identification
      of single L. monocytogenes cells as well as colonies in a non-destructive manner,
      was developed. Five different fluorescent labels are available, and allowed
      simultaneous visual discrimination between three differently labelled strains at
      the single cell level by use of fluorescence microscopy. More than 90% of the L.
      monocytogenes host cells maintained the fluorescence tags for 40 generations. The
      fluorescence tags did not alter the invasive capacity of the L. monocytogenes
      cells in a traditional Caco-2 cell invasion assay, and visual discrimination
      between invaded bacteria carrying different fluorescent labels inside the cells
      was possible. CONCLUSION: The constructed fluorescent marker system is stable,
      easy to use, does not affect the virulence of L. monocytogenes in Caco-2 cell
      assays, and allows discrimination between differently labelled bacteria after
      internalization in these cells.

PMID- 17014741
TI  - The speciation history of the Drosophila nasuta complex.
AB  - The Drosophila nasuta subgroup of the immigrans species group is widely
      distributed throughout the South-East Asian region, consisting of morphologically
      similar species with varying degrees of reproductive isolation. Here, I report
      nucleotide variability data for five X-linked and two mtDNA loci in eight taxa
      from the nasuta subgroup, with deeper sampling from D. albomicans and its sister
      species D. nasuta. Phylogenetic relationships among these species vary among
      different genomic regions, and levels of genetic differentiation suggest that
      this species group diversified only about one million years ago. D. albomicans
      and D. nasuta share nucleotide polymorphisms and are distinguished by relatively
      few fixed differences. Patterns of genetic differentiation between this species
      pair are compatible with a simple isolation model with no gene flow. Nucleotide
      variability levels of species in the nasuta group are comparable to those in
      members of the melanogaster and pseudoobscura species groups, indicating
      effective population sizes on the order of several million. Population genetic
      analyses reveal that summaries of the frequency distribution of neutral
      polymorphisms in both D. albomicans and D. nasuta generally fit the assumptions
      of the standard neutral model. D. albomicans is of particular interest for
      evolutionary studies because of its recently formed neo-sex chromosomes, and our
      phylogenetic and population genetic analyses suggest that it might be an ideal
      model to study the very early stages of Y chromosome evolution.

PMID- 17014742
TI  - Spatial genetic pattern in the land mollusc Helix aspersa inferred from a 'centre
      based clustering' procedure.
AB  - The present work provides the first broad-scale screening of allozymes in the
      land snail Helix aspersa. By using overall information available on the
      distribution of genetic variation between 102 populations previously
      investigated, we expect to strengthen our knowledge on the spread of the invasive
      aspersa subspecies in the Western Mediterranean. We propose a new approach based
      on a centre-based clustering procedure to cluster populations into groups
      following rules of geographical proximity and genetic similarity. Assuming a
      stepping-stone model of diffusion, we apply a partitioning algorithm which
      clusters only populations that are geographically contiguous. The algorithm used,
      which is actually part of leading methods developed for analysing large
      microarray datasets, is that of the k-means. Its goal is to minimize the within
      group variance. The spatial constraint is provided by a list of connections
      between localities deduced from a Delaunay network. After testing each optimal
      group for the presence of spatial arrangement in the genetic data, the inferred
      genetic structure was compared with partitions obtained from other methods
      published for defining homogeneous groups (i.e. the Monmonier and SAMOVA
      algorithms). Competing biogeographical scenarios inferred from the k-means
      procedure were then compared and discussed to shed more light on colonization
      routes taken by the species.

PMID- 17014743
TI  - Comparative gene mapping in Arabidopsis lyrata chromosomes 6 and 7 and A.
      thaliana chromosome IV: evolutionary history, rearrangements and local
      recombination rates.
AB  - We have increased the density of genetic markers on the Arabidopsis lyrata
      chromosomes AL6 and AL7 corresponding to the A. thaliana chromosome IV, in order
      to determine chromosome rearrangements between these two species, and to compare
      recombination fractions across the same intervals. We confirm the two
      rearrangements previously inferred (a reciprocal translocation and a large
      inversion, which we infer to be pericentric). By including markers around the
      centromere regions of A. thaliana chromosomes IV and V, we localize the AL6
      centromere, and can localize the breakpoints of these chromosome rearrangements
      more precisely than previously. One translocation breakpoint was close to the
      centromere, and the other coincided with one end of the inversion, suggesting
      that a single event caused both rearrangements. At the resolution of our mapping,
      apart from these rearrangements, all other markers are in the same order in A.
      lyrata and A. thaliana. We could thus compare recombination rates in the two
      species. We found slightly higher values in A. thaliana, and a minimum estimate
      for regions not close to a centromere in A. lyrata is 4-5 centimorgans per
      megabase. The mapped region of AL7 includes the self-incompatibility loci (S
      loci), and this region has been predicted to have lower recombination than
      elsewhere in the genome. We mapped 17 markers in a region of 1.23 Mb surrounding
      these loci, and compared the approximately 600 kb closest to the S-loci with the
      surrounding region of approximately the same size. There were significantly fewer
      recombination events in the closer than the more distant region, supporting the
      above prediction, but showing that the low recombination region is very limited
      in size.

PMID- 17014744
TI  - Upper limit of the rate and per generation effects of deleterious genomic
      mutations.
AB  - Unbiased or upper limit estimates of the rate (U) of genomic mutations to mildly
      deleterious alleles are crucial in genetic and conservation studies and in human
      health care. However, only a few estimates of the lower bounds of U are
      available. We present a fairly robust estimation that yields an upper limit of U
      and a nearly unbiased estimate of the per generation fitness decline due to new
      deleterious mutations. We applied the approach to three species of the freshwater
      microcrustacean Daphnia and revealed that the upper limit of U for egg
      survivorship is 0.73 (SD = 0.30) in 14 D. pulicaria populations. For the first
      four clutches, per generation decline in fecundity due to deleterious mutations
      ranged from 2.2% to 7.8% in 20 D. pulex populations and from 1.1% to 5.1% in 8 D.
      obtusa populations. These results indicate the mutation pressure is high in
      natural Daphnia populations. The approach investigated here provides a potential
      way to quickly and conveniently characterize U and per generation effects of
      deleterious genomic mutations on fitness or its important components such as
      fecundity.

PMID- 17014746
TI  - Electrophoretic separation of human skeletal muscle myosin heavy chain isoforms:
      the importance of reducing agents.
AB  - An electrophoretic protocol previously used for the separation of rat myosin
      heavy chain (MHC) isoforms was slightly modified to improve the separation of
      human MHC isoforms in both large and minigel systems. The addition of reducing
      agents (beta-mercaptoethanol or dithiothreitol) to the top running buffer (TRB)
      radically improved separated MHC isoform resolution and the intensity of
      electrophoretic runs lasting longer than 5 h. In minigel systems, the MHC
      isoforms could be separated in as little as 5 h. The improved resolution of bands
      with the inclusion of reducing agents to the TRB facilitated the identification
      of clear boundaries for densitometric quantification of relative MHC isoform
      content, particularly for MHC IIa and MHC IIx. No significant effect of these
      reducing agents added to the TRB was observed for runs lasting only 100 min. Thus
      the inclusion of reducing agents in the TRB is essential for long electrophoretic
      runs, usually when separating large molecular mass proteins.

PMID- 17014747
TI  - Clinical effectiveness and cost-effectiveness of tests for the diagnosis and
      investigation of urinary tract infection in children: a systematic review and
      economic model.
AB  - OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary
      tract infection (UTI) in children under 5 years of age and to evaluate the
      effectiveness of tests used to investigate further children with confirmed UTI.
      Also, to evaluate the effectiveness of following up children with UTI and the
      cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow
      up of UTI in children under 5. An additional objective was to develop a
      preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES:
      Electronic databases were searched up to the end of 2002/early 2003. Consultation
      with experts in the field. REVIEW METHODS: A systematic review was undertaken
      using published guidelines and results were analysed according to test grouping:
      diagnosis of UTI and further investigation of UTI. The cost-effectiveness results
      from existing evaluations were synthesised. A separate cost-effectiveness model
      was developed using the best available evidence, in part derived from the results
      of the systematic review, to illustrate the potential cost-effectiveness of some
      alternative management strategies in a UK setting. The results of the systematic
      review were used to propose diagnostic algorithms for the diagnosis and further
      investigation of UTI in children. Economic analyses did not contribute directly
      to the development of these algorithms. RESULTS: The studies included in the
      review provided very little data on the accuracy of clinical investigations for
      the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further
      defined. The majority of studies included in the review found that clean voided
      midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA)
      samples when cultured with the advantage of being a non-invasive collection
      method that can be used in the GP's surgery. Pad, nappy or bag specimens may be
      appropriate methods for obtaining a urine sample in non-toilet-trained children,
      although only limited data were available. Although the glucose test was reported
      to have the highest accuracy in terms of both ruling in and ruling out disease,
      only a limited number of studies of this test were included and these were
      conducted over 30 years ago. Dipstick tests are easy to perform in the GP's
      surgery, give an immediate result and are relatively cheap. The results of the
      systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite,
      where both test results are interpreted in combination, was a good test both for
      ruling in (both positive) and ruling out (both negative) a UTI. A dipstick
      positive for either LE or nitrite and negative for the other provides
      inconclusive diagnostic information and further testing is therefore required in
      these patients. Microscopy is more time consuming and expensive to perform than a
      dipstick test, but potentially quicker and cheaper than culture. As with dipstick
      tests, a combination of microscopy for pyuria and bacteriuria can be used
      accurately to rule in and rule out a UTI. An indeterminate test result is again
      obtained if microscopy is positive for either pyuria or bacteriuria, and negative
      for the other. Confirmatory culture is required in these patients. In patients
      considered to have a UTI, further culture to determine antibiotic sensitivities
      may be an option to inform treatment decisions. Only one study satisfied the
      inclusion criteria of the economic review and the review highlighted a number of
      potential limitations of this study for NHS decision-making. A separate decision
      analytic model was therefore developed to provide a more reliable estimate of the
      optimal strategy regarding the diagnosis and further investigation of children
      under 5 with suspected UTI from the perspective of the NHS. The economic model
      found that the optimal diagnostic strategy for children presenting with symptoms
      suggestive of UTI depends on a number of key factors. These included the relevant
      subgroup of children concerned, in terms of gender and age, and the health
      service's maximum willingness to pay for an additional quality-adjusted life
      year. CONCLUSIONS: The results of the systematic review were used to derive an
      algorithm for the diagnosis of UTI in children under 5. This algorithm represents
      the conclusions of the review in terms of effective practice. There were
      insufficient data to propose an algorithm for the further investigation of UTI in
      children under 5. The quality assessment highlighted several areas that could be
      improved upon in future diagnostic accuracy studies.

PMID- 17014748
TI  - Cognitive behavioural therapy in chronic fatigue syndrome: a randomised
      controlled trial of an outpatient group programme.
AB  - OBJECTIVES: To test the hypothesis that group cognitive behavioural therapy (CBT)
      will produce an effective and cost-effective management strategy for patients in
      primary care with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).
      DESIGN: A double-blind, randomised controlled trial was adopted with three arms.
      Outcomes were assessed at baseline and 6 and 12 months after first assessment and
      results were analysed on an intention-to-treat basis. SETTING: A health
      psychology department for the management of chronic illness in a general hospital
      in Bristol, UK. PARTICIPANTS: Adults with a diagnosis of CFS/ME referred by their
      GP. INTERVENTIONS: The three interventions were group CBT incorporating graded
      activity scheduling, education and support group (EAS) and standard medical care
      (SMC). OUTCOME MEASURES: The primary outcome measure was the Short Form with 36
      Items (SF-36) physical and mental health summary scales. Other outcome measures
      included the Chalder fatigue scale, Hospital Anxiety and Depression Scale,
      General Health Questionnaire, physical function (shuttles walked, walking speed
      and perceived fatigue), health utilities index and cognitive function (mood,
      recall and reaction times). RESULTS: A total of 153 patients were recruited to
      the trial and 52 were randomised to receive CBT, 50 to EAS and 51 to SMC. Twelve
      patients failed to attend for the 12-month follow-up and 19 patients attended one
      follow-up, but not both. The sample was found to be representative of the patient
      group and the characteristics of the three groups were similar at baseline. Three
      outcome measures, SF-36 mental health score, Chalder fatigue scale and walking
      speed, showed statistically significant differences between the groups. Patients
      in the CBT group had significantly higher mental health scores [difference +4.35,
      95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference
      -2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference
      +2.83 shuttles, 95% CI +1.12 to +5.53, p = 0.0013) than patients in the SMC
      group. CBT patients also walked faster and were less fatigued than those
      randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to +3.51, p =
      0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no
      other statistically significant difference across the groups was found, although
      for many measures a trend towards an improved outcome with CBT was seen. Except
      for walking speed, which, on average, increased by +0.87 shuttles (95% CI +0.09
      to +1.65, p = 0.029) between the 6- and 12-month follow-ups, the scores were
      similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical
      score within the normal range and 52% had an SF-36 mental health score in the
      normal range. At 12 months, the physical score was in the normal range for 46% of
      the CBT group, 26% of the EAS group and 44% of SMC patients. For mental health
      score the percentages were CBT 74%, EAS 67% and SMC 70%. Of the CBT group, 32%
      showed at least a 15% increase in physical function and 64% achieved a similar
      improvement in their mental health. For the EAS and SMC groups, this improvement
      in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53%
      (SMC), respectively. The cost-effectiveness of the intervention proved very
      difficult to assess and did not yield reliable conclusions. CONCLUSIONS: Group
      CBT did not achieve the expected change in the primary outcome measure as a
      significant number did not achieve scores within the normal range post
      intervention. The treatment did not return a significant number of subjects to
      within the normal range on this domain; however, significant improvements were
      evident in some areas. Group CBT was effective in treating symptoms of fatigue,
      mood and physical fitness in CFS/ME. It was found to be as effective as trials
      using individual therapy in these domains. However, it did not bring about
      improvement in cognitive function or quality of life. There was also evidence of
      improvement in the EAS group, which indicates that there is limited value in the
      non-specific effects of therapy. Further research is needed to develop better
      outcome measures, assessments of the broader costs of the illness and a clearer
      picture of the characteristics best fitted to this type of intervention.

PMID- 17014749
TI  - Combining the old with the new to improve therapeutics.

PMID- 17014750
TI  - An easy approach to evaluating peripheral neuropathy.

PMID- 17014751
TI  - Endarterectomy for carotid artery stenosis: who qualifies?

PMID- 17014752
TI  - Important questions before flu season.

PMID- 17014753
TI  - Oral contraceptives and breakthrough bleeding: what patients need to know.

PMID- 17014754
TI  - Skin lesions mimicking septic arthritis.

PMID- 17014755
TI  - Trials and tribulations of becoming a family medicine colonoscopist: a personal
      story.

PMID- 17014756
TI  - Clinical inquiries. What common substances can cause false positives on urine
      screens for drugs of abuse?

PMID- 17014757
TI  - Clinical inquiries. Do allergy shots help seasonal allergies more than
      antihistamines and nasal steroids?

PMID- 17014758
TI  - Clinical inquiries. What is the prognostic value of stress echocardiography for
      patients with atypical chest pain?

PMID- 17014759
TI  - Clinical inquiries. Can patients with steatohepatitis take statins?

PMID- 17014760
TI  - Clinical inquiries. What are appropriate screening tests for adolescents?

PMID- 17014761
TI  - Clinical inquiries. What are effective treatments for oppositional defiant
      behaviors in adolescents?

PMID- 17014762
TI  - Polyelectrolytic aspects of the titration curve. The semi-flexible model.
AB  - An analysis is given of the theoretical approach to the quantitative description
      of proton dissociation curves for weak polyacids. The basic model of the
      counterion condensation theory has been used, with the modification reported in
      the preceding study (S. Paoletti, A. Cesaro, C. Arce Samper and J.C. Benegas,
      Biophys. Chem. 34 (1989) 301). In this paper we demonstrate the effect of
      relaxing the hypothesis of a rigid conformation on the polyelectrolytic
      properties of weak polyacids. As an application of the present approach, a
      description is given of the titration curves for two weak polyacids, poly(DL
      glutamic acid) (PDLGA) and poly(L-aspartic acid) (PLAA).

PMID- 17014763
TI  - Polyelectrolytic aspects of the titration curve. pH-induced conformational
      transition of poly(L-glutamic acid): the semi-flexible model.
AB  - The cooperative conformational transition of poly(L-glutamic acid) induced by pH
      is monitored by the titration curves from literature. The polyelectrolytic
      approach described in the preceding article (A. Cesaro, S. Paoletti and J.C.
      Benegas, Biophys. Chem. 39 (1991) 1) is used to fit the experimental curves under
      various conditions of ionic strength and temperature, with the sole assumption
      that each polymeric state is characterized by a proper conformational
      flexibility. The helix-coil transition of the system becomes molecularly defined
      by the balance between the non-ionic conformational energy and the repulsive
      electrostatic energy of the two forms. Implications of the results of the
      theoretical model on the energetics of the cooperative order-disorder transition
      are discussed.

PMID- 17014764
TI  - Anthracycline gels. Preparation and some physico-chemical properties.
AB  - Gels have been prepared from aqueous solutions of anthracyclines by addition of
      salts. The gels are thixotropic and thermally reversible. They are stable for
      several months in the refrigerator and for long times even at room temperature.
      The gel-solution transition (melting) temperature depends on the concentration of
      the anthracycline and on the concentration and nature of the added salt. The
      melting has been followed by 1H-NMR. Only weak intermolecular interactions
      (stacking and hydrogen bonds) originate the drug network, within which the
      solvent is entrapped. 1H-NMR and polarimetric data suggest a stacked helical
      arrangement of the anthracycline molecules. The gelation process is cooperative.

PMID- 17014765
TI  - Intramolecular excimer formation of pyrene-labeled lipids in lamellar and
      inverted hexagonal phases of lipid mixtures containing unsaturated
      phosphatidylethanolamine.
AB  - The rates of intramolecular excimer formation of di(1'
      pyrenemyristoyl)phosphatidylcholine (dipyPC) in dioleoylphosphatidylethanolamine
      (DOPE), egg PE/diolein (DG) and dilinoleoyl-PE (DLPE)/1-palmitoyl-2-oleoyl-PC
      (POPC) were studied at different temperatures and lipid compositions. Both the
      excimer-to-monomer intensity ratio and the excimer association rate constant were
      employed to quantify the rate of excimer formation. The latter was calculated
      from the measured monomer fluorescence lifetime of dipyPC. We observed that the
      rate of excimer formation was sensitive to either the temperature-induced or
      lipid composition-induced lamellar-to-inverted hexagonal phase transition of the
      above lipid systems. As the lipids entered the inverted hexagonal phase, the rate
      of excimer formation increased at the temperature-induced phase transition for
      DOPE, but decreased at the composition-induced phase transition for both TPE/DG
      and DLPE/POPC systems by increasing the DG% and decreasing the PC%, respectively.
      We conclude that the rate of intramolecular excimer formation of dipyPC in the
      non-lamellar phase is influenced both by the intra-lipid free volume of the
      hydrocarbon region and the intra-rotational dynamics of the two lipid acyl
      chains.

PMID- 17014766
TI  - Simulation of an oscillatory reaction of alcohol dehydrogenase in an oil/water
      system.
AB  - With numerical analysis of the enzyme-catalyzed reaction in the so called
      'ordered bi-bi' mechanism and the model presented by Theorell and Chance (Acta
      Chem. Scand. 5 (1951) 1127) for alcohol dehydrogenase, oscillations of the
      concentrations of coenzyme and intermediate complex were obtained on gradual
      entry of substrate. Neither autocatalysis nor allostery was included in the
      reaction mechanism. The features of the reaction were that the oscillations did
      not occur in a limit cycle and the interval became longer with time. In addition,
      it was found that the oscillations with an upwardly directed peak occurred at
      very low concentrations of enzyme in the model of Theorell and Chance. The
      results were consistent with the experimentally determined data reported
      previously.

PMID- 17014767
TI  - Insulin association in neutral solutions studied by light scattering.
AB  - Molecular weights and weight distributions of sulfated, Zn-free, and 2Zn insulins
      have been measured at pH 7.3 as a function of concentration from 0.1 to 2 mg/ml
      by use of a combination of light scattering, refractometry, and size-exclusion
      chromatography. Results show that sulfated insulin is monomeric over the studied
      concentration range. Weight average molecular weights between those of a monomer
      and a hexamer were found for both zinc-free and 2Zn insulins. Zinc stabilizes the
      hexamer, and the dimer-hexamer equilibrium constant is approx. 400-times higher
      in the presence of zinc than in its absence. An average hydrodynamic radius of
      5.6 nm, close to the crystallographic size of the insulin hexamer, was determined
      from dynamic light scattering of 2Zn insulin solutions.

PMID- 17014768
TI  - Protein and chlorophyll in photosystem II probed by infrared spectroscopy.
AB  - The infrared spectra of photosystem II (PS II) enriched submembrane fractions
      isolated from spinach are obtained in water and in heavy water suspension Other
      spectra are obtained after a photooxidation reaction was performed on PS II to
      bleach the pigments. The water bands are removed by computer subtraction and the
      amide bands (A, B, I, II, and III) of the protein are identified. Computer
      enhancement techniques are used to narrow the bandwidth of the bands that the
      weak chlorophyll bands, buried in the much stronger protein bands, can be
      observed. Comparing the spectra of native and photooxidized PS II pr in water and
      in heavy water, we determine that three polypeptide domains are present in the
      native material. The first domain, which contains 22% of th is situated in the
      peripheral region of the PS II system. The polypeptides in this region are
      unfolded and devoid of chlorophyll. The second domain con of the polypeptides, is
      more organized, and contains the chlorophylls. The third domain has an alpha
      helix configuration, does not contain chlorophyll, a affected by the
      photooxidation reaction or by the proton/deuteron exchange. Three different types
      of chlorophyll organisation are identified: two have carbonyl groups non-bonded,
      differing from one another only in their hydrophobic milieux; the third is weakly
      bonded to another unidentified group. Other forms of chlorophyll organisation are
      present but could not be observed because their absorption is buried in the
      protein amide I band.

PMID- 17014769
TI  - Anisotropy decays of indole, melittin monomer and melittin tetramer by frequency
      domain fluorometry and multi-wavelength global analysis.
AB  - We used frequency-domain fluorescence spectroscopy to measure the fluorescence
      lifetime and anisotropy decays of indole in propylene glycol, and of the
      tryptophan emission of melittin monomer and tetramer in water solutions at 5
      degrees C. We obtained an increase in resolution of the anisotropy decays by
      using multiple excitation wavelengths, chosen to provide a range of fundamental
      anisotropy values. The multi-excitation wavelength anisotropy decays were
      analyzed globally to recover a single set of correlation times with wavelength
      dependent anisotropy amplitudes. Simulated data and kappaR2 surfaces are shown to
      reveal the effect of multi-wavelength data on the resolution of complex
      anisotropy decays. For both indole and melittin, the anisotropy decays are
      heterogeneous and require two correlation times to fit the frequency-domain data.
      For indole in propylene glycol at 5 degrees C we recovered correlation times of
      0.59 and 4.10 ns, which appear to be characteristic of the rigid and asymmetric
      indole molecule. For melittin monomer the correlation times were 0.13 and 1.75
      ns, and for melittin tetramer 0.12 and 3.96 ns. The shorter and longer
      correlation times of melittin are due to segmental motions and overall rotational
      diffusion of the polypeptide.

PMID- 17014770
TI  - Investigation of ionic stability criteria for ion-permeable charged membranes.
AB  - The flocculation criteria in the DLVO theory of colloid stability are applied to
      ion-permeable membranes containing ionizable fixed groups. These groups are not
      restricted to the membrane surface but are uniformly distributed throughout a
      thick surface layer. The flocculation concentrations for such membranes are
      calculated by using a numerical method to solve the nonlinear Poisson-Boltzmann
      equation. Results are compared with calculations previously carried out for more
      restrictive models of biological membranes. The flocculation concentrations are
      shown to depend on the density of ionizable groups, the dissociation constant of
      these groups, and the pH of the bulk solution.

PMID- 17014771
TI  - Calculation of the optimal surface area for amphiphile molecules using the hard
      core method.
AB  - In this work, we have calculated the optimal surface area per amphiphile molecule
      using a two-dimensional gas of electric dipoles interacting with hard The optimal
      surface area can be evaluated according to a formula (in the two-body
      approximation) or as a root of an equation (in the three-body approximation). If
      the equation has more than one positive root, which is greater than the hard core
      area, then a polydisperse dimensional distribution of supramolecular aggregates
      is possible.

PMID- 17014772
TI  - Development of an equation for potentiometric titration of polyelectrolytes using
      a periodic lattice model. A numerical analysis of interactions among ionizable
      groups.
AB  - A numerical method is presented for analysing the potentiometric titration
      behavior of linear polyelectrolytes. A polyelectrolyte molecule is treated as a
      one-dimensional lattice containing a large number of lattice points, each of
      which has an identical ionizable group. In this method, the polyelectrolyte model
      lattice is divided into identical repeating unit cell systems with a finite
      number of ionizable groups to calculate the thermodynamic partition function of
      the system of polyelectrolyte solution. The electrostatic interaction between
      ionized groups adopted in the present study is given by the Debye-Huckel type
      screened Coulombic potential. The titration behavior as well as several
      thermodynamic quantities is derived by making a canonical ensemble summation of
      all states in a unit cell system under an appropriate periodic boundary
      condition. This method serves as a model of the two-step ionization often
      appearing in polyions with strong neighboring interactions such as homo- and
      copolymers of maleic acid. Several characteristics of the titration behavior of
      these polyelectrolytes are well reproduced by using a lattice model with pairwise
      intervals, including the effects of hydrogen bond formation and change in
      dielectric constant of the medium around an ionizable group. In addition, this
      method is valid for a more detailed analysis of the titration behavior of
      polyelectrolytes with various kinds of arrangements of charged groups.

PMID- 17014773
TI  - Study of an error-prone hypercycle formed from two kinetically distinguishable
      species.
AB  - Asymmetry within both the amplification factor values (Ak) and cross-catalytic
      hypercyclic constant (Kjk) and its influence on the stability of a two-membered
      error-prone hypercycle has been exhaustively studied from a deterministic point
      of view and the bifurcation diagram as a function of the quality factor (Q) has
      been obtained. In the more general case, several Q critical values appear,
      changing their relative position in the diagram depending on the Ak and Kjk
      values. The order of the Q critical values affects both the general properties of
      the system and the stability of the hypercyclic organization. The importance of
      this asymmetry in the selective and evolutionary properties of the hypercycle is
      also discussed.

PMID- 17014774
TI  - Enzyme-inhibitor complexes of lysozyme with glucosamine inhibitors. A molecular
      dynamics study through 2H-NMR.
AB  - 2H relaxation measurements coupled with multiple specific 2H labeling have
      provided insight into the molecular dynamics of N-acetyl-D-glucosamine (GlcNAc)
      inhibitors bound to lysozyme. Deuteron T1 and T2 data for the bound state of
      methyl alpha- and -beta-GlcNAc 2H-labeled in the glycosidic methyl and C2
      positions have been derived from measurements at different enzyme/inhibitor
      ratios. Rotational correlation times calculated therefrom for the labeled sites
      indicate, in both cases, tight binding for the sugar ring (tau(b) = 3.0 x 10(-9)
      s) accompanied by fast internal rotation, about one axis, of the glycosidic
      methyl groups (tau(r) = 5.5-7.6 x 10(-11) s). The small but consistent difference
      in the rates of internal rotation for the alpha- and beta-anomeric inhibitors may
      be indicative of different solution structures of the enzyme-inhibitor complexes.

PMID- 17014775
TI  - Characterization of proline-containing right-handed alpha-helix by molecular
      dynamics studies.
AB  - Proline residues play a special role in shaping the secondary and tertiary
      structures of proteins. Many of these aspects have been studied in great detail.
      Current interest lies in elucidating the structure of right-handed alpha-helical
      fragments which contain proline in the middle of the helix. Such structures play
      an important role in membrane proteins and in the tight packing of globular
      proteins. Analysis of several crystal structures and energy minimization using
      flexible geometry have elucidated the nature of the bend produced by proline in
      the right-handed alpha-helical structure. Molecular dynamics (MD) simulation
      studies are ideally suited to characterize rigidity or flexibility in different
      parts of the molecule and can also give an idea of various conformations of the
      molecule which can exist at a given temperature. Hence, MD studies on Ace-(Ala)6
      Pro-(Ala)3-NHMe have been carried out for 100 ps after equilibration and the
      resulting trajectories have been analyzed. Information regarding the average
      values, r.m.s. fluctuations of internal parameters and the time spent in
      different conformations are discussed. Energy minimization has been carried out
      on selected MD simulated points in order to analyze the characteristics of
      different conformations.

PMID- 17014776
TI  - Dynamics of electron transfer in the oxidation of water by chlorophyll a dimer.
AB  - The observed temperature dependence of the rate constant for reduction of (Chl
      a.2H2O)2+. by water is fitted to a theoretical expression for the rate of an
      intramolecular electronic radiationless transition. The theory assumes a single
      effective mediating mode and the best-fit value for the frequency of this mode is
      omega(m) = 680 cm(-1), which corresponds to high-frequency, intermolecular
      librations in water. From an explicit calculation of the nonadiabatic-coupling
      matrix element, an average electron-transfer distance of 11 A is obtained,
      consistent with molecular dimensions available for this system.

PMID- 17014777
TI  - A short period oscillation in a water/oil/water system.
AB  - A new kind of potential oscillation with a short period of 7.5 s was found to
      occur in a water/oil/water system which consisted of an aqueous solution of
      surfactant, nitrobenzene and an aqueous solution of NaCI. A long period
      (approximately 10 min) oscillation previously reported was also found to be
      superposed on the new oscillation. The power spectrum of the short period
      oscillation has been measured.

PMID- 17014778
TI  - Induced dipole moment of purple membranes. Theoretical analysis.
AB  - The induced dipole moment of a purple membrane parallel to the membrane surface
      was analysed based on the two-dimensional fluctuation theory of counterions. The
      observed polarizability previously measured by electric dichroism and its
      dependence on the membrane size were derived from theory for the case where the
      interaction between counterions was screened. The screening effect of salts on
      the induced dipole moment was estimated from the theory on diffuse double layers.

PMID- 17014779
TI  - Chemiluminescence study on the peroxidation of linoleic acid initiated by the
      reaction of ferrous iron with hydrogen peroxide.
AB  - Linoleic acid was used as a model system to study lipid peroxidation initiated by
      the reaction of ferrous iron with hydrogen peroxide. Low-level chemiluminescence
      of the peroxidation was measured with a high-sensitivity single-photon counter.
      It was found that the luminescence primarily comes from the dimol reaction of
      singlet oxygen and that the peak intensity of emission is a quadratic function of
      the concentration of either Fe2+ or H2O2, provided that the other Fenton reagent
      is in great excess. Under the same conditions, analysis on reaction kinetics
      shows a linear relationship between the maximal level of the initiator formed by
      the Fenton reaction and the initial concentration of Fe2+ or H2O2. This implies
      that the peak intensity of the chemiluminescence may be a good index of the
      maximal level of the initiator.

PMID- 17014780
TI  - A dynamical model for phospholipid-calcium binding.
AB  - A model for an isothermal gel-liquid crystalline transition induced by ionic
      binding is proposed. A Ginsburg-Landau functional was used to describe the long
      range order that spontaneously arises during the transition. By calculation of
      the corresponding chemical potential we obtain the mass current of phospholipids
      in gel-phase described by an order parameter. In the conservation of mass
      equation the kinetics of the phospholipids-calcium interaction is introduced,
      together with the flux divergency. A circular membrane is considered for the
      analysis, so that the model can be studied in polar coordinates. A solution
      approximated to first order shows an heterogeneous distribution of domains of
      phospholipids in gel and liquid crystalline phases. These spatial domains have
      been detected experimentally by diverse methods in vesicles and cellular
      membranes. Spatial heterogeneities may cause destabilization of the membrane in
      the boundaries between domains. This may explain the enhanced vesicle fusion
      observed in the presence of Ca2+.

PMID- 17014781
TI  - Thermodynamics of the disproportionation of adenosine 5'-diphosphate to adenosine
      5'-triphosphate and adenosine 5'-monophosphate. I. Equilibrium model.
AB  - The thermodynamic treatment of the disproportionation reaction of adenosine 5'
      diphosphate to adenosine 5'-triphosphate and adenosine 5'-monophosphate is
      discussed in terms of an equilibrium model which includes the effects of the
      multiplicity of ionic and metal bound species and the presence of long range
      electrostatic and short range repulsive interactions. Calculated quantities
      include equilibrium constants, enthalpies, heat capacities, entropies, and the
      stoichiometry of the overall reaction. The matter of how these calculations can
      be made self-consistent with respect to both calculated values of the ionic
      strength and the molality of the free magnesium ion is discussed. The
      thermodynamic data involving proton and magnesium-ion binding data for the
      nucleotides involved in this reaction have been evaluated.

PMID- 17014782
TI  - Thermodynamics of the disproportionation of adenosine 5'-diphosphate to adenosine
      5'-triphosphate and adenosine 5'-monophosphate, II. Experimental data.
AB  - High-pressure liquid-chromatography and microcalorimetry have been used to
      determine equilibrium constants and enthalpies of reaction for the
      disproportionation reaction of adenosine 5'-diphosphate (ADP) to adenosine 5'
      triphosphate (ATP) and adenosine 5'-monophosphate (AMP). Adenylate kinase was
      used to catalyze this reaction. The measurements were carried out over the
      temperature range 286 to 311 K, at ionic strengths varying from 0.06 to 0.33 mol
      kg(-1), over the pH range 6.04 to 8.87, and over the pMg range 2.22 to 7.16,
      where pMg = -log a(Mg2+). The equilibrium model developed by Goldberg and Tewari
      (see the previous paper in this issue) was used for the analysis of the
      measurements. Thus, for the reference reaction: 2 ADp(3-) (ao) AMp(2-) (ao)+ ATp-
      (ao), K degrees = 0.225 +/- 0.010, DeltaG degrees = 3.70 +- 0.11 kJ mol (-1),
      DeltaH degrees = -1.5 +/- 1. 5 kJ mol (-1), degrees S degrees = -17 +/- 5 J mol(
      1)K(-1), and ACP(p) degrees approximately = -46 J mo1l(-1)K(-1) at 298.15 K and
      0.1 MPa. These results and the thermodynamic parameters for the auxiliary
      equilibria in solution have been used to model the thermodynamics of the
      disproportionation reaction over a wide range of temperature, pH, ionic strength,
      and magnesium ion morality. Under approximately physiological conditions (311.15
      K, pH 6.94, [Mg2+] = 1.35 x 10(-3) mol kg(-1), and I = 0.23 mol kg(-1)) the
      apparent equilibrium constant (KA' = m(SigmaAMP)m(SigmaATP)/[ m(SigmaADP)]2) for
      the overall disproportionation reaction is equal to 0.93 +/- 0.02. Thermodynamic
      data on the disproportionation reaction and literature values for this apparent
      equilibrium constant in human red blood cells are used to calculate a morality of
      1.94 x 10(-4) mol kg(-1) for free magnesium ion in human red blood cells. The
      results are also discussed in relation to thermochemical cycles and compared with
      data on the hydrolysis of the guanosine phosphates.

PMID- 17014783
TI  - Interfacial thermodynamics of protein adsorption, ion co-adsorption and ion
      binding in solution. I. Phenomenological linkage relations for ion exchange in
      lysozyme chromatography and titration in solution.
AB  - In this paper we discuss the thermodynamics of ion binding in solution, protein
      adsorption and ion co-adsorption. The emphasis is on charge regulation effects.
      To this end, we introduce phenomenological linkage relations from which the ion
      binding can be calculated from the electrolyte dependency of proton titration
      curves and the co-adsorption from the electrolyte dependency of protein
      adsorption isotherms. The linkage relations are derived from classical
      interfacial thermodynamics, and thus offer an alternative approach as compared to
      the mass balance equations which are currently used in biotechnology, and Record
      et al.'s 1978 analysis of Wyman's Binding Polynomial for protein interactions.
      The co-adsorption theory is an extension of our previous analysis of ion binding
      in solution, which we include here for comparison of the ion co-adsorption with
      the ion binding in solution. The theory is applied to the chromatography of
      lysozyme on the strong cation exchanger 'mono S' and to the proton titration of
      lysozyme in solution. In the accompanying Part 2 of this paper the results are
      interpreted with a simple model.

PMID- 17014784
TI  - Interfacial thermodynamics of protein adsorption, ion co-adsorption and ion
      binding in solution. II. Model interpretation of ion exchange in lysozyme
      chromatography.
AB  - In this paper we present a model for the ion exchange effects in protein
      adsorption. The model is applied to chromatography of lysozyme on strong cation
      exchanger 'mono S'. The experimental and general thermodynamic aspects have been
      discussed in Part 1, the preceding paper. The main modelling assumptions are (i)
      the charge regulation is confined to the small layer of contact between adsorbed
      protein and exchanger surface, (ii) the contact layer as a whole is
      electroneutral and (iii) the number of protein acid/base groups and exchanger
      surface acid groups which participate in the ion exchange is proportional to the
      area of the contact layer. The model is fitted to the experimental data by
      adjustment of only two or three parameters. The experimental co-adsorption
      numbers are very well reproduced. A few conspicuous features emerge: (i) the
      number of protein acid/base groups and exchanger surface acid groups in the
      contact layer varies with the medium conditions, such that the number is higher
      when the interaction between protein and exchanger surface is stronger. (ii)
      There is indirect evidence for structural alterations in the upper layers of the
      exchanger surface: the adsorbed protein is probably partly 'buried' in the
      surface.

PMID- 17014785
TI  - Michel Mandel 65. Preface.

PMID- 17014786
TI  - Viscosity and scattering of very weakly charged polyelectrolytes.
AB  - Careful examination of the concentration range where both intrinsic viscosity and
      light scattering show a polyelectrolyte effect, even for singly charged halato
      telechelic ionomers in DMF, together with the neutron scattering results at
      higher concentration show that weakly charged polymers may be a very useful tool
      to understand the complicated effects of coulombic interaction in polyelectrolyte
      solutions. A theoretical framework is given for a systematic study of such weakly
      charged polymers. The current state of understanding is presented of the
      properties of solutions of strong polyelectrolytes and of charged rigid
      particles. Finally it is shown how the transposition to weak polyelectrolytes
      solutions sheds light on the respective contributions of intra- and
      intermolecular interactions.

PMID- 17014787
TI  - The charge structure function in electrolytes and polyelectrolytes.
AB  - The relation between charge and dielectric structure functions is examined in the
      case of electrolytes and polyelectrolytes. When the coupling constant is larger
      than unity, characteristic features should be observed on the dielectric
      structure function, in addition to the classical screening effect. We point our
      the existence of experimental conditions which provide direct information of the
      dielectric structure at shorter wavelength (lambda 1 nm). They correspond to zero
      average contrast in scattering experiments.

PMID- 17014788
TI  - Growth of linear charged micelles.
AB  - The electrostatics of micellar growth is reviewed and extended for solutions
      containing excess salt. In dilute solution the expansion of a linear micelle with
      increasing salt concentration is explained for a wide range of ionic strength.
      When the micellar charge density is very high, counterions condense nonuniformly
      onto the micellar rod. In that case the micelle may contract upon the addition of
      salt. In semidilute solutions the excluded-volume effect is an additional factor
      complicating the ionic strength dependence of micellar growth.

PMID- 17014789
TI  - Electroviscosity of polyelectrolyte solutions.
AB  - A theoretical expression for the electroviscous effect in polyelectrolyte
      solutions, caused by the distortion of counterion-distribution and counterion
      flow around a polyion under a velocity gradient of solvent flow, was obtained to
      elucidate the characteristic behaviour of the viscosity of highly charged
      polyelectrolyte solutions observed at low salt concentration. The derivation of
      the theory was performed on the basis of the Navier-Stokes-Onsager equation,
      Poisson equation, and diffusion equations for low molecular ions by the use of a
      cell model (free-volume model) for a polyion. Energy dissipation was obtained
      without directly solving these equations. It was found that the derived
      expression of viscosity explained the experimental results satisfactorily, and
      that the streaming potential effect caused by the counterion flow played an
      essential role in the increase in viscosity of polyelectrolyte solutions at
      finite polymer concentration and low salt concentration ranges.

PMID- 17014790
TI  - When and why is the random force in Brownian motion a Gaussian process.
AB  - It is shown that the assumptions of causality and time-reversal invariance
      severely restrict the possibility to describe the fluctuations of a variable in a
      non-linear Markovian system using a Langevin equation. In fact a theorem is
      proven which implies that with the aforementioned assumptions a Langevin force
      which is independent of the state of the system is necessarily Gaussian and
      white. The theorem furthermore implies that such a description is only possible
      if the socalled "systematic force" is proportional to the derivative of the
      logarithm of the equilibrium distribution of the variable. Our analysis is given
      for a system with one variable which may be either even or odd under time
      reversal.

PMID- 17014791
TI  - Limiting-laws of polyelectrolyte solutions. Ionic distribution in mixed-valency
      counterions systems. I: The model.
AB  - An extension of the counterion-condensation (CC) theory of linear
      polyelectrolytes has been developed for the case of a system containing a mixture
      of counterions of different valency, i and j. The main assumption in the
      derivation of the model is that the relative amount of the condensed counterions
      of the type i and j is strongly correlated and it is determined by the overall
      physical bounds of the system. The results predicted by the model are consistent,
      in the limiting cases of single species component, with those of the original CC
      theory. The most striking results are obtained for the cases of low charge
      density and excess of counterion species: in particular, an apparent positive
      "binding" cooperativity of divalent ions is revealed for small, increasing
      additions of M2+ ions to a solution containing a swamping amount of monovalent
      salt and a polyelectrolyte of low charge density. Apparent "competitive binding"
      of mono- and divalent ions derives as a bare consequence of the electrostatic
      interactions. Theoretical calculations of experimentally accessible quantities,
      namely single-(counter) ion activity coefficients, confirm the surprising
      predictions at low charge density, which qualitatively agree with the measured
      quantities.

PMID- 17014792
TI  - Counter-ion dynamics in crosslinked poly(styrene sulfonate) systems studied by
      NMR.
AB  - The field dependence of the longitudinal and transverse nuclear magnetic
      relaxation rates of 23Na+ in aqueous crosslinked Na-poly(styrene sulfonate) (PSS)
      systems (ion exchange resins) has been obtained as a function of the degree of
      crosslinking. The relaxation is considerably enhanced relative to solutions of
      non-crosslinked NaPSS at equal ionizable group concentration. This is due to the
      dynamic constraints of the polymer chains, which render the averaging of the
      counter-ion chain interaction less efficient. The field dependence of the
      relaxation rates in the crosslinked NaPSS systems reveals two processes that are
      out of the extreme narrowing limit. This is in contrast to the relaxation
      behavior found in non-crosslinked NaPSS systems. To characterize these processes
      their correlation times were combined with constants of selfdiffusion to estimate
      the distances diffused by an ion in order to average the electric field gradient
      at its nucleus. These two distances are interpreted as characteristic length
      scales in the network. At all degrees of crosslinking it was found that the
      smallest of these length scales is roughly equal to the distance between two
      neighbouring crosslinks. The largest characteristic distance extends over several
      crosslinks and reflects inhomogeneities in the crosslink concentration. These
      conclusions were also reached from similar experiments on 7Li+ in LiPSS systems.

PMID- 17014793
TI  - Charge formation in microporous membranes by single-acid site dissociation.
AB  - The electrolyte concentration and pH dependence of the effective charge density
      of weak ion exchange membranes have been studied by combining solutions of the
      Poisson-Boltzmann equation in cylindrical pores with a simple dissociation
      equilibrium of weakly acid groups attached to the pore walls. Analytical
      expressions for the effective charge density and wall potential are presented
      which describe these quantities in terms of pH, electrolyte (1 : 1)
      concentration, acid constant, density of acid groups and the pore size. The
      concentration dependence of the effective fixed charge density experimentally
      observed for cellulose membranes and NaCl-solutions agrees quantitatively with
      the theoretical predictions. For track-etched mica membranes and KCl-solutions
      the influence of pH and electrolyte concentration on the effective charge density
      can be qualitatively explained. Also an interpretation of electro-osmotic
      findings obtained with an asymmetric cellulose acetate membrane and NaCl
      solutions is given.

PMID- 17014794
TI  - Inhibition of photophosphorylation and electron transport by N,N
      dimethylformamide.
AB  - The basal electron transport of pea chloroplasts was inhibited by 78% by 7% (v/v)
      N,N-dimethylformamide; the inhibition was partially reversed by NH4Cl. N,N
      Dimethylformamide also inhibited the Pi-ATP exchange, ATP synthesis and to a
      smaller extent Mg2+-ATPase activity. Light induced proton uptake was not affected
      by up to 30% (v/v) N,N-dimethylformamide. Uncoupled electron transport in
      photosystem II was inhibited to a larger extent by N,N-dimethylformamide than in
      photosystem I. These results indicate that N,N-dimethylformamide acts as an
      inhibitor of energy transfer and electron transport.

PMID- 17014795
TI  - The time resolved fluorescence and anisotropy of subtilisins BPN' and Carlsberg.
AB  - Time-resolved emission and anisotropy have been measured for the tryptophan (Trp)
      residues of two closely related subtilisin proteins. The single Trp of subtilisin
      Carlsberg shows complex lifetime properties, and anisotropy consistent with a
      fast (ca. 200 ps) segmental motion, on the "wobbling in a cone model" the semi
      angle is in the range 38 to 47 degrees. The lifetime and anisotropy properties
      for this single Trp residue suggest that the predominant state is that of an
      effectively non-emitting statically quenched fluorophore. This fast component is
      also resolved in the anisotropy of subtilisin BPN' but with relatively low
      amplitude, due to the dominant emission of the other Trp residues. The diversity
      of the photophysical properties is not readily correlated with the structure of
      the proteins, though the observed complexity is consistent with the likely
      heterogeneity of environment due to the surface location of all the Trp residues.

PMID- 17014796
TI  - The coupling of catalytically relevant conformational fluctuations in subtilisin
      BPN' to solution viscosity revealed by hydrogen isotope exchange and inhibitor
      binding.
AB  - We have measured the tritium outexchange of subtilisin BPN'. A consistent and
      rather small group of hydrogens was isolated by their sensitivity to inhibitor
      binding. The viscosity dependence of exchange from these inhibitor protected
      hydrogens was then examined in 0.05 M MES buffer, pH 6.5 and 10 degrees C. The
      viscosity of the reaction medium was varied by added glycerol and ethylene
      glycol. The exchange rates were corrected to be compared at identical hydroxyl
      ion and water activity. The salient observation is the strikingly similar
      viscosity coupling behavior when compared to the deacylation step of ester
      hydrolysis catalyzed by the same enzyme (Ng and Rosenberg, Biophysical Chemistry,
      39 (1991) 57). We have obtained a viscosity coupling constant of 0.68 -/+ 0.18
      for hydrogen exchange in glycerol (cf. 0.65 -/+ 0.11 for deacylation in glycerol,
      sucrose, glucose and fructose); 1.67 -/+ 0.07 for outexchange (cf. 1.92 -/+ 0.09
      for deacylation), in the presence of ethylene glycol. The two reactions are very
      chemically dissimilar, yet they show very similar viscosity coupling behavior.
      This together with the well established role of structural fluctuations in
      hydrogen exchange implies a similar role of structural fluctuations in the
      deacylation step of subtilisin BPN' catalyzed ester hydrolysis.

PMID- 17014797
TI  - Further studies on membrane transport with time delay.
AB  - A theory of cell membrane transport with a time delay which predicts under
      certain conditions overshoot or oscillatory permeation (Ohshima and Kondo,
      Biophys. Chem. 33 (1989) 303), is extended with the introduction of a parameter
      expressing a fraction of solutes inside the cell interior that suffer time delay.
      It is found that criterion for oscillation depends strongly on this parameter.
      Results will also be presented for the case of an exponential-type distribution
      of the delay time.

PMID- 17014798
TI  - An adsorption isotherm for the interaction of membrane-permeable hydrophobic ions
      with lipid vesicles.
AB  - An adsorption isotherm is presented which describes the association of membrane
      permeable hydrophobic ions with lipid vesicles. The theory is based upon the
      Langmuir adsorption isotherm, but is has been significantly extended to take into
      account diffusion of ions across the membrane and dissociation into the
      intravesicular space as well as electrical effects due to the build up of
      boundary potentials within the membrane. The boundary potentials are calculated
      according to the three-capacitor model of the lipid membrane. In contrast to the
      Gouy-Chapman theory, which is only applicable when the charged group is located
      directly at the membrane-solution interface, the theory presented here allows the
      charge to be located at any position within the membrane.

PMID- 17014799
TI  - Analysis of time-resolved emission spectra of oriented phycobilisomes.
AB  - The polarized time-resolved (in ps range) fluorescence spectra of phycobilisomes
      obtained from cyanobacteria Tolypothrix tenuis embedded in poly(vinyl alcohol)
      films and oriented by film stretching have been analysed. Fluorescence spectra
      were deconvoluted on Gaussian components supposing the same positions of
      components maxima in three sets of time-resolved spectra taken in natural and
      polarized light. A good fit of the experimental and calculated spectra was
      obtained when using the following maxima: 580 and 595 nm in the phycoerythrin
      region, 634 and 650 nm in the phycocyanin region, 660 and 680 nm in the
      allophycocyanin region. The area under curve of the Gaussian component vs. time
      gives the shape of rise and decay of emission of chromophores contributing to the
      given component. These kinetics were analysed using several model functions. The
      experimental excitation profile was convoluted with a multiexponential model
      individually or "globally" e.g. assuming the same lifetime values for the given
      species in all sets of spectra. The Foerster-Hauser types of two- and three
      dimensional models we also convoluted with excitation profile and fitted to the
      decay of primarily excited species. The first acceptor decay can be described
      well by the Foerster-Hauser models or by a monoexponential function. The accuracy
      of fit in either case of three- and two-dimensional Foerster-Hauser function is
      similar. The fluorescence rise and decay of the next species in a donor-acceptor
      chain can be analysed in terms of two or three exponential functions. Obtained
      lifetimes of fluorescence are similar to those reported in literature. The
      results suggest that there are more than one chain of excitation donors and
      acceptors in the phycobilisomes of cyanobacteria Tolypothrix tenuis.

PMID- 17014800
TI  - Monte Carlo simulation of the conformational behaviour of a polypeptide chain
      near a charged surface.
AB  - The conformational behaviour of a short polypeptide chain in the neighbourhood of
      a charged plane is simulated using a Monte Carlo method. In this approach, the
      plane is taken as a model of an interface separating a hydrophobic region from a
      hydrophilic one. It is shown that in the neighbourhood of the plane, folded
      molecular conformations are prevailing whilst stretched conformations are
      preferred far from the interface. When the plane is not charged, the molecule
      adjusts itself parallel to the interface. For a given position of the molecule
      with respect to the plane, when the charge density of the plane is increased, the
      molecule tends to turn perpendicular to the plane. The surface may either attract
      or repulse the molecule depending on the value of the charge density (the plane
      is always negatively charged).

PMID- 17014801
TI  - Voltage-dependent capacitance as a probe for albumin adsorption onto a solid
      surface.
AB  - The process of adsorption of bovine serum albumin onto a platinum electrode was
      monitored through the measurement of a nonlinear electrochemical property. The
      principle of the new method is that a sinusoidal voltage source is applied to a
      test solution and the waveform of the output current is analyzed by Fourier
      transformation. It was found that the intensities of the higher harmonics in the
      Fourier transformation change depending on the concentration of albumin and with
      time. From the higher harmonics, voltage dependence of the capacitance was
      quantitatively evaluated. The change of the state of albumin adsorbed onto the
      platinum plate was also monitored from the pattern of 'crack' of adsorbed albumin
      by using scanning electron microscopy. These results were discussed in relation
      to the mechanism of bimodal adsorption of albumin.

PMID- 17014802
TI  - Melting characteristics of highly supercoiled DNA.
AB  - The effect of high supercoil densities on the melting characteristics of a
      supercoiled DNA has been studied. It is found that although the melting
      temperature increases abruptly on converting a linear DNA merely into the relaxed
      circular form, it falls back substantially at high supercoil densities. It is
      further predicted, in such cases, that the number of melted base pairs should be
      significantly enhanced even at the physiological temperature, which may
      facilitate the binding of other molecules to the highly supercoiled DNA.

PMID- 17014803
TI  - Solvation of beta-lactoglobulin in alkylurea solutions.
AB  - Solvation of beta-lactoglobulin in aqueous solutions of urea, methyl-, N,N'
      dimethyl- and ethylurea was studied by density measurements. From the densities
      at constant chemical potential and constant molality, the preferential solvation
      parameters and the partial specific volumes of beta-lactoglobulin in these
      solutions were determined. In urea and methylurea solutions urea is
      preferentially bound, whereas in N,N'-dimethyl- and ethylurea solutions at higher
      concentration water is preferentially bound. From preferential solvation data and
      partial specific volumes of protein Gibbs free energies of transfer from water to
      alkylurea solutions were calculated. Since the enthalpies of transfer were
      determined previously the entropies of transfer could also be obtained so that a
      complete thermodynamic description is available. An attempt is made to interpret
      the values of the thermodynamic quantities in terms of various interactions
      involved in solvation. In salvation of alkylureas the hydrophobic nature of alkyl
      groups is clearly reflected.

PMID- 17014804
TI  - Limiting-laws of polyelectrolyte solutions. Ionic distribution in mixed-valency
      counterions systems. II. A comparison of conductometric data and theoretical
      predictions.
AB  - The competitive binding of monovalent and divalent counterions (M+ and M2+,
      respectively) has been studied by a conductometric procedure as described by De
      Jong et al. (Biophysical Chemistry 27 (1987) 173) for aqueous solutions of alkali
      metal polymethacrylates in the presence of Ca (NO3)2 or Mg(NO3)2. The
      experimentally obtained fractions of conductometrically free counterions are
      compared with theoretical values computed according to a new thermodynamic model
      recently developed by Paoletti et al. (Biophysical Chemistry, 41 (1991) 73). For
      the systems studied, the fractions of free monovalent and divalent counterions
      can be fairly well described by the theory. In fact, the results support the
      assumption that under the present conditions the conductometrically obtained
      distribution parameters (l) and (2) approximate the equilibrium fractions of free
      monovalent and divalent counterions. For a degree of neutralization of 0.8 and a
      molar concentration ratio of divalent counterions and charged groups on the
      polyion up to 0.25, the mean M+/M2+, exchange ratio nu has been found to be 1.39
      +/- 0.03 and 1.33 +/- 0.03 for the alkali metal/Ca/PMA and alkali metal/Mg/PMA
      systems, respectively. These values agree well with the theoretical value, which
      for this particular case is 1.38.

PMID- 17014805
TI  - Are all-terrain vehicle injuries becoming more severe?
AB  - BACKGROUND: There are several reasons to suspect that injuries from all-terrain
      vehicles (ATV) have become both more serious and frequent in recent years. These
      reasons include increasing engine power, younger age of operators and
      inconsistent enforcement of helmet laws. The purpose of this study was to
      determine if the increase in ATV injuries was out of proportion to the increase
      in ATV usage and whether ATV injuries have increased in severity. METHODS: A
      retrospective analysis of the Consumer Product Safety Commission (CPSC) ATV
      injury data and the Pennsylvania Trauma System Foundation (PTSF) database from
      1989 to 2002 was performed. ATV use, sales, deaths, trauma center admissions,
      Injury Severity Score (ISS), hospital length of stay (LOS) and Glascow Coma Score
      (GCS) were reviewed. RESULTS: ATV sales increased to 316%. In the decade prior to
      2003, reported deaths nationally increased from 183 to 357 (95%) nationally and
      from 5 to 10 (100%) in Pennsylvania (PA). Admissions to trauma centers in PA
      increased 240%, yet the percentage of deaths to trauma center admissions remained
      constant at 2.6% during this period (p>.50). ISS and LOS from 1989 to 2002 did
      not significantly change (all p>.05) and GCS improved significantly. CONCLUSION:
      Despite concerns regarding the increasing dangers associated with ATVs, it
      appears that the severity of injuries from ATV use has not increased.

PMID- 17014806
TI  - A bibliometric analysis of global trends of research productivity in tropical
      medicine.
AB  - The field of tropical medicine has a long history due to the significance of the
      relevant diseases for the humanity. We estimated the contribution of different
      world regions to research published in the main journals of tropical medicine.
      Using the PubMed and the Institute for Scientific Information (ISI) "Web of
      Science" databases, we retrieved articles from 12 journals included in the
      "Tropical Medicine" category of the "Journal Citation Reports" database of ISI
      for the period 1995-2003. Data on the country of origin of the research were
      available for 11,860 articles in PubMed (98.1% of all articles from the tropical
      medicine category). The contribution of different world regions during the
      studied period, as estimated by the location of the affiliation of the first
      author, was: Western Europe 22.7%, Africa 20.9%, Latin America and the Caribbean
      20.7%, Asia (excluding Japan) 19.8%, USA 10.6%, Oceania 2.1%, Japan 1.5%, Eastern
      Europe 1.3%, and Canada 0.6%. The contribution of regions, estimated by the
      location of the affiliation of at least one author of the published papers
      (retrieved from the ISI database), was similar: Western Europe 36.6%, Africa
      27.7%, Latin America and the Caribbean 24.4%, and Asia 23.3%. The mean impact
      factor of articles published in tropical medicine journals was highest for the
      USA (1.65). Our analysis suggests that the developing areas of the world produce
      a considerable amount of research in tropical medicine; however, given the
      specific geographic distribution of tropical diseases they probably still need
      help by the developed nations to produce more research in this field.

PMID- 17014807
TI  - Three- and four-dimensional ultrasonography for the structural and functional
      evaluation of the fetal face.
AB  - Ultrasonographic examination of the fetal face can provide information that may
      lead to the diagnosis of anomalies in other organs or systems. Thus, the fetal
      face represents a "diagnostic window" for fetal diseases and syndromes. Three
      dimensional ultrasonography (3DUS) improves the evaluation of anatomic fetal
      facial anomalies over what is possible by 2-dimensional ultrasonography (2DUS).
      Four-dimensional ultrasonography (4DUS), by adding the temporal component to the
      examination, allows visualization of facial expressions that might be useful in
      the study of fetal behavior and maternal-fetal bonding. In this article, we
      evaluate the potential of 3D/4DUS for the study of structural and functional
      development of the fetal face.

PMID- 17014809
TI  - Impact of hospital and surgeon volumes on outcomes following pelvic
      reconstructive surgery in the United States.
AB  - OBJECTIVE: The purpose of this study was to estimate the effect of hospital and
      surgeon volumes on outcomes following urogynecologic surgery. STUDY DESIGN: This
      was a retrospective cohort study of women who underwent urogynecologic procedures
      between 1998 and 2003 from the Nationwide Inpatient Sample. Hospitals and
      surgeons were categorized as low, medium, or high volume based on average number
      of cases per year. Outcomes included in-hospital mortality, complications, and
      nonroutine discharges. Multivariable analyses were performed using generalized
      estimation equations to estimate relative risks. RESULTS: There were 310,759
      women and 2986 hospitals. Women who had procedures at low-volume hospitals were
      2.75 (95% CI 2.33-3.16) times more likely to die and 1.63 (95% CI 1.44-1.83)
      times more likely to have a nonroutine discharge, compared to those at high
      volume hospitals. Women who had procedures by low-volume surgeons were also more
      likely to suffer complications and have nonroutine discharges compared to those
      with high-volume surgeons. CONCLUSION: Differences in hospital and surgeon
      volumes of urogynecologic procedures may contribute to variations in mortality
      and morbidity risks.

PMID- 17014810
TI  - Is transobturator tape as effective as tension-free vaginal tape in patients with
      borderline maximum urethral closure pressure?
AB  - INTRODUCTION: The purpose of this study was to compare transobturator tape
      (MONARC) with tension-free vaginal tape in patients with borderline low maximum
      urethral closure pressure. STUDY DESIGN: Historical cohort analysis of 3-month
      outcomes in 145 subjects (MONARC = 85; tension-free vaginal tape = 60). A cut-off
      point of 42 cm H2O for preoperative maximum urethral closure pressure was
      identified as predictor of success in the entire cohort. The cohort was
      stratified by sling type and analyzed. Outcome variables included urodynamic
      stress incontinence, urethral pressure profiles, subjective stress incontinence
      symptoms, and complications. RESULTS: The relative risk of postoperative
      urodynamic stress incontinence 3 months after surgery in patients with a
      preoperative maximum urethral closure pressure of 42 cm or less H2O was 5.89
      (1.02 to 33.90, 95% confidence interval) when we compared MONARC with tension
      free vaginal tape. Subjects in the MONARC and tension-free vaginal tape groups
      did not differ significantly in baseline characteristics. We defined subjects as
      failures if they demonstrated postoperative objective stress incontinence on
      multichannel urodynamic testing. CONCLUSION: In subjects with maximum urethral
      closure pressure of 42 cm or less H2O, the MONARC was nearly 6 times more likely
      to fail than tension-free vaginal tape at 3 months after surgery. Long-term
      follow-up and randomized controlled trials are needed.

PMID- 17014811
TI  - Will an adverse pregnancy outcome influence the risk of continued smoking in the
      next pregnancy?
AB  - OBJECTIVE: The purpose of this study was to study the effect of pregnancy
      outcomes on risks of continued smoking in subsequent pregnancy. STUDY DESIGN:
      Cohort study of first and second single births among 98,778 Swedish women who
      were daily smokers in first pregnancy. RESULTS: In all, 70.2% of women continued
      to smoke in second pregnancy. Compared with women with a previous normal
      pregnancy outcome, risk of smoking in second pregnancy was increased among women
      with a previous small-for-gestational-age birth (adjusted odds ratio [OR], 95% CI
      1.28 [95% CI 1.19-1.37]), and reduced among women who had experienced a
      stillbirth (OR 0.76 [95% CI 0.63-0.93]) or an infant death because of congenital
      malformations (OR 0.67 [95% CI 0.49-0.92]. A previous preterm birth, Sudden
      Infant Death Syndrome, and other causes of infant death did not influence risk.
      CONCLUSION: A previous adverse pregnancy outcome has only a modest influence on
      smoking habits in the successive pregnancy.

PMID- 17014812
TI  - Sensory nerve injury after uterosacral ligament suspension.
AB  - OBJECTIVE: Uterosacral ligament suspension is a technique that is performed
      commonly to suspend the prolapsed vaginal apex. This case series describes our
      experience with the clinical evaluation and management of lower extremity sensory
      nerve symptoms after uterosacral ligament suspension. STUDY DESIGN: Hospital and
      office medical records from our 2 institutions were reviewed from January 2002 to
      August 2005, and all women who underwent uterosacral ligament suspension through
      a vaginal approach were identified. Women with symptoms of buttock and posterior
      thigh pain during the 6-week postoperative period were identified, and detailed
      clinical information was abstracted from the charts. RESULTS: From 182
      uterosacral ligament suspension procedures, 7 women were identified. The age
      range was 42 to 70 years. Concurrent procedures included 6 vaginal
      hysterectomies, 5 anterior repairs, 4 posterior repairs, 2 slings, and 1
      bilateral salpingo-oophorectomy. Within 24 hours of the surgical procedure, all
      the women experienced similar, substantial sharp buttock pain and numbness that
      radiated down the center of the posterior thigh to the popliteal fossa in 1 or
      both lower extremities. The ipsilateral uterosacral ligament suture was removed
      within 2 days of the procedure in 3 women who had immediate subjective reduction
      in their pain and complete resolution of pain by 6 weeks. The remaining 4 women
      were treated with gabapentin and narcotics. Three women had resolution of the
      pain by 12 to 14 weeks after the operation, and the last woman's pain resolved
      gradually by 6 months. CONCLUSION: Women who undergo uterosacral ligament
      suspension are at risk of postoperative pain and numbness in a S2-4 distribution.
      These symptoms appear to be related to the placement of uterosacral ligament
      sutures and may be relieved either by prompt removal of the ipsilateral
      uterosacral ligament suture or with prolonged medical therapy.

PMID- 17014813
TI  - Maternal-fetal conditions necessitating a medical intervention resulting in
      preterm birth.
AB  - OBJECTIVE: The objective of the study was to evaluate the extent to which
      maternal and fetal conditions necessitate medically indicated preterm birth.
      STUDY DESIGN: A population-based, retrospective, cohort study of women who
      delivered a singleton live birth at 20 weeks or longer in Missouri, 1989 to 1997
      was performed (n = 684,711). Maternal-fetal conditions that necessitated
      iatrogenic preterm birth included preeclampsia, small-for-gestational-age birth,
      fetal distress, placental abruption, placenta previa, unexplained vaginal
      bleeding, pregestational and gestational diabetes, renal disease, Rh
      sensitization, and congenital malformations. We examined the association between
      each of the aforementioned conditions and risk of medically indicated preterm
      birth at less than 35 weeks. Medically indicated preterm birth was defined as a
      labor induction or a prelabor cesarean in the absence of premature rupture of
      membranes at preterm gestations. Adjusted relative risk with 95% confidence
      interval for preterm birth was derived from multivariable logistic regression
      models, and population attributable fractions were calculated. RESULTS: The
      preterm birth rate (less than 35 weeks) was 4.6% (n = 31,238), with 23.5% (n =
      7,347) of such births being medically indicated. Preeclampsia, fetal distress,
      small-for-gestational-age, and placental abruption were the most common
      indications for a medical intervention resulting in preterm birth, with at least
      1 of these conditions present in 53.2% of medically indicated preterm births and
      in 17.7% of term births (relative risk 4.9, 95% confidence interval 4.7, 5.2).
      CONCLUSION: Preeclampsia, fetal distress, small-for-gestational-age, and
      placental abruption, conditions that are associated with ischemic placental
      disease, are implicated in well over half of all medically indicated preterm
      births. Although the etiology of preterm birth is heterogeneous, it is reasonable
      that ischemic placental disease may serve as an important pathway to preterm
      birth.

PMID- 17014814
TI  - Sexual function in women with urodynamic stress incontinence, detrusor
      overactivity, and mixed urinary incontinence.
AB  - OBJECTIVE: This study was undertaken to compare sexual function in sexually
      active women with urodynamic stress incontinence (USI), detrusor overactivity
      (DO), and mixed urinary incontinence (MUI). STUDY DESIGN: We reviewed the medical
      records of all women evaluated for urinary incontinence (UI) at our institution
      between March 2003 and August 2004. At the time of initial evaluation, all women
      completed the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual
      Function Questionnaire (PISQ-12). PISQ-12 scores of age-matched women with
      urodynamic diagnoses of USI, DO, and MUI were compared. Statistical analysis was
      performed with 1-way analysis of variance and chi2 contingency table analysis.
      RESULTS: Fifty women with USI, 50 with DO, and 48 with MUI were included in this
      study. Subject demographics were similar among the 3 groups. Mean PISQ-12 scores
      did not differ significantly among the 3 groups. CONCLUSION: Among sexually
      active women with urinary incontinence, sexual function as assessed by the PISQ
      12 does not differ according to type of incontinence.

PMID- 17014816
TI  - Obesity and retropubic surgery for stress incontinence: is there really an
      increased risk of intraoperative complications?
AB  - OBJECTIVE: The objective of the study was to evaluate the impact of obesity on
      length of surgery, blood loss, and intra- and postoperative complications in
      women who underwent retropubic surgery for stress urinary incontinence. STUDY
      DESIGN: Of 449 women participating in a multicenter, randomized trial evaluating
      antibiotic prophylaxis in women with suprapubic catheters, 250 women underwent
      retropubic anti-incontinence procedures. This is a prospective nested cohort
      study of these women, 79 (32%) of whom were obese (body mass index 30 or greater)
      and 171 (68%) overweight or normal weight (body mass index less than 30). Data
      collected included demographic variables, past medical history, physical
      examination, and intraoperative and postoperative complications. Data were
      analyzed with Fisher's exact for dichotomous variables, Student t tests for
      continuous variables, and analysis of variance for multivariate analysis.
      Significance was set at P < .05. RESULTS: Obese women undergoing stress urinary
      incontinence surgery were younger than nonobese women (48.7 versus 51.9 years,
      respectively, P < .019). The number and type of additional surgeries performed
      were similar between groups with the exception that obese women were less likely
      to undergo abdominal apical suspensions (P = .006) or abdominal paravaginal
      repairs (P = .001); therefore, estimated blood loss, change in hematocrit, length
      of stay, surgery, and suprapubic catheterization comparisons are adjusted for the
      performance of these procedures. Estimated surgical blood loss was greater for
      obese women (344 versus 284 P = .03); however, change in hematocrit was lower for
      obese than nonobese women (6.6 versus 7.3, P = .048). Mean length of surgery was
      15 minutes longer in obese women (P = .02). Length of hospital stay did not vary
      between groups (P = NS). Major intraoperative complications were uncommon (14
      [5.6%]), with no difference between weight groups. Incidence of postoperative
      urinary tract infection, wound infections, or postoperative major complications
      were likewise similar between groups (all P > .05). CONCLUSION: Surgery takes
      longer for obese patients, but blood loss as recorded by change in hematocrit is
      lower. Major complications were rare and similar between weight groups, as were
      infectious complications.

PMID- 17014817
TI  - The correlation of urethral mobility and point Aa of the pelvic organ prolapse
      quantification system before and after surgery.
AB  - OBJECTIVE: The purpose of the study was to determine the effects of pelvic floor
      surgery on Q-tip angle and point Aa of the pelvic organ prolapse quantification
      system. STUDY DESIGN: A clinical database was used for this retrospective review
      of Q-tip and prolapse measurements before and after pelvic floor surgery.
      Subanalyses of isolated bladder neck and prolapse surgeries were also performed.
      Correlations between Q-tip and point Aa were assessed with Pearson and Spearman
      coefficients and the Z statistic. RESULTS: Correlations between Q-tip and point
      Aa for all 350 women were not significantly different before and after the
      operation (r = 0.45 vs 0.49; P = .50). Subanalysis of the bladder neck-only group
      demonstrated similarly fair correlations (r = 0.26 vs 0.31; P = .71; n = 94). The
      prolapse-only group demonstrated better overall correlation without significant
      differences before and after the operation (r = 0.78 vs 0.51; P = .10; n = 26).
      CONCLUSION: Point Aa does not reflect bladder neck mobility accurately as
      measured by the Q-tip angle after surgical restoration of the pelvic anatomy.

PMID- 17014818
TI  - Inhibition of ovarian cancer growth and implantation by paclitaxel after
      laparoscopic surgery in a mouse model.
AB  - OBJECTIVE: We used an established experimental model to evaluate the influence of
      intraperitoneal chemotherapy on the generation of laparoscopy-associated
      metastases and the effectiveness of chemotherapy. STUDY DESIGN: Twenty-four nude
      mice underwent laparoscopy with carbon dioxide insufflation and the instillation
      of a tumor cell suspension with or without paclitaxel into the peritoneal cavity.
      Mice were allocated to 1 of the following groups (8 mice to each group): (1)
      controls; (2) paclitaxel given during the operation; (3) paclitaxel given after
      the operation. Mice were killed 30 days after the procedure, and the peritoneal
      cavity and port sites were examined for the presence of tumors. RESULTS: Tumor
      implantation and port-site metastases were reduced more by the intraoperative
      intraperitoneal administration of paclitaxel during the operation than by
      administration after the operation. CONCLUSION: Intraoperative intraperitoneal
      administration of paclitaxel may decrease significantly the occurrence of port
      site metastasis and intraperitoneal dissemination in an animal study.

PMID- 17014819
TI  - Determinants of vaginal length.
AB  - OBJECTIVE: The purpose of this study was to describe quantitatively the
      associations between total vaginal length and demographic, historic, and physical
      characteristics. STUDY DESIGN: At 2 clinical sites, patients completed a
      standardized questionnaire and physical examination. Bivariate correlations
      explored relationships between total vaginal length and demographic, historic,
      and examination variables. Significant variables were evaluated with a
      multivariate linear regression model. RESULTS: The study included 3247 women.
      Hysterectomy and pelvic reconstructive surgery contribute 0.63 cm and 0.22 cm,
      respectively, to total vaginal length shortening; 10 years of age decreases total
      vaginal length by 0.08 cm. One meter of height and 10 kg of weight increases
      total vaginal length by 0.09 cm and 0.02 cm, respectively. Menopause is
      associated with a shortening of total vaginal length by 0.17 cm. CONCLUSION:
      Although there appears to be statistically significant associations between total
      vaginal length and the aforementioned factors, the impact is unlikely to be
      clinically significant.

PMID- 17014820
TI  - Holo- and apo-cystalysin from Treponema denticola: two different conformations.
AB  - Cystalysin, the key virulence factor in the bacterium Treponema denticola
      responsible for periodontis, is a pyridoxal 5'-phosphate (PLP) enzyme which
      catalyzes, in addition to alpha,beta-elimination of L-cysteine, racemization and
      transamination of both enantiomers of alanine. In this paper several indicators
      have been used as probes of the different conformational status of T. denticola
      cystalysin in the holo and apo form. Compared to holoenzyme, the apoenzyme
      displays an altered reactivity of cysteine residues, a significantly different
      pI, and a differential susceptibility to proteinase K. The site of cleavage that
      is accessible in apocystalysin and masked in holocystalysin has been identified
      by mass spectrometry as the peptide bond between Phe 360 and Gly 361. This
      cleavage results in the loss of the C-terminal fragment corresponding to a
      molecular mass of 4289.21+/-0.1Da. The major fragment of cleaved enzyme retains
      its dimeric structure, binds the coenzyme with an affinity approximately 5000
      fold lower than that of uncleaved holoenzyme, and in the reconstituted form is
      able to form the external aldimine with substrates. Although the break causes the
      loss of lyase, racemase and transaminase activities of D-alanine, it does not
      abolish the transaminase activity of L-alanine. Possible mechanistic and
      physiological implications are proposed.

PMID- 17014821
TI  - The state transition mechanism - simply depending on light-on and -off in
      Spirulina platensis.
AB  - The state transition in cyanobacteria is a long-discussed topic of how the
      photosynthetic machine regulates the excitation energy distribution in balance
      between the two photosystems. In the current work, whether the state transition
      is realized by "mobile phycobilisome (PBS)" or "energy spillover" has been
      clearly answered by monitoring the spectral responses of the intact cells of the
      cyanobacterium Spirulina platensis. Firstly, light-induced state transition
      depends completely on a movement of PBSs toward PSI or PSII while the redox
      induced one on not only the "mobile PBS" but also an "energy spillover".
      Secondly, the "energy spillover" is triggered by dissociation of PSI trimers into
      the monomers which specially occurs under a case from light to dark, while the
      PSI monomers will re-aggregate into the trimers under a case from dark to light,
      i.e., the PSI oligomerization is reversibly regulated by light switch on and off.
      Thirdly, PSI oligomerization is regulated by the local H(+) concentration on the
      cytosol side of the thylakoid membranes, which in turn is regulated by light
      switch on and off. Fourthly, PSI oligomerization change is the only mechanism for
      the "energy spillover". Thus, it can be concluded that the "mobile PBS" is a
      common rule for light-induced state transition while the "energy spillover" is
      only a special case when dark condition is involved.

PMID- 17014822
TI  - Glutamate, water and ion transport through a charged nanosize pore.
AB  - The transport of transmitter, ions and water through a positively-charged
      nanopore was investigated through computer simulations. The physics of the
      problem is described by a coupled set of Poisson-Nernst-Planck and Navier-Stokes
      equations in a computational domain consisting a cylindrical pore, whose radius
      ranged from 1 to 8 nm and which was flanked by two compartments representing the
      vesicular interior and extra-cellular space. The concentration of co-ions is
      suppressed and of counter-ions enhanced, especially near the pore wall owing to
      electrostatic interactions. Glutamate (i.e. the transmitter considered) is
      negatively charged and is simulated as a counter-ion. The electro-kinetically
      induced pressure due to the movement of ions is negative and very pronounced near
      the pore wall where the concentration and flux of counter-ions is very high. The
      water velocity peaks in the pore center, diminishes to zero at the pore wall, but
      is constant along the pore axis. The mean velocity of the water/fluid is
      proportional to the vesicular pressure and pore cross-sectional area.
      Interestingly it is inversely related to the vesicular glutamate concentration.
      The factors determining the glutamate flux are complex. The diffusive flux
      generally predominates for narrow pore, and convective flux may dominate for wide
      pore if the vesicular pressure is high. Surprisingly at low vesicular pressure
      the mean total glutamate flux per unit cross-sectional pore area is higher for
      narrow pores. Higher flux is probably due to the rise of glutamate concentration
      in the nanopore, which is much more pronounced for narrow nanopores, due to the
      maintenance of approximate neutrality of charges in the pore and on the pore
      wall. In conclusion intra-vesicular pressure helps 'flushing-out' the
      transmitter, but the induced pressure 'drags-out' the water into the extra
      cellular space.

PMID- 17014823
TI  - The Spanish language version of the Eating Disorder Examination Questionnaire:
      comparison with the Spanish language version of the eating disorder examination
      and test-retest reliability.
AB  - This study compared the Spanish language questionnaire (S-EDE-Q) and interview (S
      EDE) versions of the Eating Disorder Examination and examined the short-term test
      retest reliability of the questionnaire version. Seventy-seven monolingual
      Spanish-speaking Latina women recruited from the community completed the S-EDE-Q
      and were then administered the S-EDE by fully bilingual doctoral-level research
      clinicians. The same assessment was repeated after approximately one week (5-14
      days). The S-EDE-Q and the S-EDE were significantly correlated on frequencies of
      binge eating and all four subscales. Mean differences in the frequency of binge
      eating and the Restraint subscale were not significant, but scores on the Eating
      Concern, Weight Concern, and Shape Concern subscales differed significantly, with
      the S-EDE-Q yielding higher scores. Test-retest reliability for the S-EDE-Q was
      modest for binge eating but was excellent for the subscales (Spearman rho ranged
      0.71-0.81), albeit somewhat variable for the individual items. Overall, the
      acceptable convergence between the S-EDE-Q and the S-EDE for many features of
      eating disorders and the good short-term test-retest findings provide preliminary
      support for the use of the S-EDE-Q. These findings, derived using a non-clinical
      sample of monolingual Spanish-speaking Latina women, require replication and
      extension. Evaluation with a clinical sample is necessary to further establish
      the reliability of the S-EDE-Q with an eating disordered group.

PMID- 17014824
TI  - Cognitive aspects of nonclinical obsessive-compulsive hoarding.
AB  - Research on the cognitive variables associated with obsessive-compulsive hoarding
      is scarce. In this study, we investigated cognitive variables that may contribute
      to the maintenance and possibly etiology of hoarding. College students who
      characterized themselves as either "packrats" (nonclinical hoarders; n=21) or not
      (control participants; n=20) completed questionnaires assessing hoarding behavior
      and beliefs about hoarding, and completed a task requiring them to categorize
      diverse objects and trinkets of minimal value into groups. The results revealed
      that nonclinical hoarders, relative to control participants, rated the
      categorization task as significantly more stressful and difficult. Relative to
      control participants, hoarders took longer to complete the task and sorted
      objects into more categories. These findings suggest that underinclusiveness and
      indecisiveness, characteristic of clinical hoarders, are evident in nonclinical
      hoarders as well.

PMID- 17014825
TI  - The effects of different types of goal pursuit on experience and performance
      during a stressful social task.
AB  - Researchers have recently suggested that anxiety research may benefit from the
      examination of motivational factors, such as the difference between approach and
      avoidance goals. This suggestion is consistent with the literature on self
      regulation, which indicates that affect serves as feedback for goal pursuit, with
      anxiety primarily providing feedback regarding avoidance. However, no data are
      available on participant goals for a task that generates social anxiety. Data
      from 120 speech anxious participants who engaged in a public speaking task were
      used to test the following hypotheses: (1) avoidance goals would be more specific
      than approach goals; (2) goals regarding social anxiety would have a negative
      impact on public speaking experience and performance; and (3) participants would
      tend to organize approach and avoidance goals not as separate goals, but as
      opposite poles of the same overarching goal. Hypotheses (1) and (3) were fully
      supported and hypothesis (2) was partially supported. The results highlight the
      possibility that approach goals may be particularly important to anxiety
      reduction.

PMID- 17014826
TI  - Involvement of early growth response gene 1 in the modulation of microsomal
      prostaglandin E synthase 1 by epigallocatechin gallate in A549 human pulmonary
      epithelial cells.
AB  - The prostaglandin E(2) (PGE(2)) can play critical roles in the pulmonary
      inflammation or carcinogenesis. It is the first investigation of the effect of a
      green tea polyphenol, (-)-epigallocatechin gallate (EGCG), on the PGE(2)
      producing microsomal prostaglandin E synthase 1 (mPGES-1) expression in the lung
      alveolar type II pneumocytes, A549 cells as an epithelial model. EGCG enhanced
      cyclooxygenase (COX)-2 and mPGES-1 gene expression as well as PGE(2). Among
      several tea catechins, EGCG was most effective in inducing mPGES-1 expression.
      Moreover, even in the cytokine-stimulated cells, mPGES-1 protein was super
      induced by EGCG treatment. As signaling mediators in mPGES-1 induction by EGCG,
      active ERK1/2 MAP kinases and early growth response gene 1 (EGR-1) were increased
      after exposure to EGCG. Moreover, EGCG stimulated the nuclear translocation of
      the EGR-1 protein in A549 cells through ERK signaling pathway. Recent studies
      demonstrate that EGR-1 is a key transcription factor in mPGES-1 gene expression.
      When blocking the gene expression of EGR-1 with EGR-1 siRNA or ERK inhibitor,
      EGCG-induced mPGES-1 was suppressed in both cases. mPGES-1 promoter with deleted
      or point-mutated EGR-1 binding sites showed significantly less response to the
      EGCG stimulation, which also implicated the importance of EGR-1 binding in
      promoting mPGES-1 gene expression. Taken all, EGCG was strong inducer of EGR-1
      expression and mediated EGR-1 nuclear translocation via ERK signaling pathway in
      A549 pulmonary epithelial cells. Induced EGR-1 then stimulated the induction of
      mPGES-1 gene expression and this effect mechanistically can be linked to the
      pharmacological or toxicological actions after human exposure to green tea
      catechins.

PMID- 17014827
TI  - Relationship of catechol-O-methyltransferase variants to brain structure and
      function in a population at high risk of psychosis.
AB  - BACKGROUND: There is growing evidence that the gene catechol-O-methyltransferase
      (COMT) is involved in the etiopathogenesis of schizophrenia. This study sought to
      clarify the effects of the COMT Val158Met polymorphism on brain structure,
      function, and risk of developing schizophrenia in a well-characterized cohort of
      individuals at high risk of schizophrenia for familial reasons. METHODS: In a
      sample of 78 people at high genetic risk of schizophrenia, the risk of
      progression to schizophrenia associated with the COMT Val allele was estimated.
      The relationship of the Val allele to brain structure and function was
      investigated using structural magnetic resonance imaging (sMRI) and functional
      magnetic resonance imaging (fMRI) data collected on the high-risk subjects before
      their disease outcome was known. RESULTS: The COMT Val allele increased the risk
      of schizophrenia in this cohort in a dose-dependent manner. Subjects with the
      COMT Val allele had reduced gray matter density in anterior cingulate cortex. In
      addition, there was evidence of increased activation in lateral prefrontal cortex
      and anterior and posterior cingulated, with increasing sentence difficulty in
      those with the COMT Val allele despite a similar level of performance.
      CONCLUSIONS: The COMT Val allele is associated with an increased risk of
      schizophrenia in subjects at increased familial risk, in whom it has demonstrable
      effects on prefrontal brain structure and function. These patterns of altered
      brain structure and function have previously been associated with schizophrenia
      in this and other samples.

PMID- 17014828
TI  - Variations in the catechol O-methyltransferase polymorphism and prefrontally
      guided behaviors in adolescents.
AB  - BACKGROUND: The catechol-O-methyltransferase (COMT) gene codes for an enzyme that
      degrades prefrontal cortex (PFC) synaptic dopamine. Of two identified alleles
      (Met and Val), the Met allele results in COMT activity that is up to 4 times less
      pronounced than that conferred by the Val allele, resulting in greater PFC
      dopamine concentrations. Met-Met homozygotes perform better than individuals who
      possess the Val allele on PFC-mediated cognitive tasks. These genotypic
      variations and their associations with executive functions have been described in
      adults and prepubescent children, but there is a paucity of research assessing
      these relations in adolescent samples. METHODS: In this study, 70 children aged 9
      17 were genotyped for COMT and completed measures of working memory, attention,
      fine motor coordination, and motor speed. RESULTS: COMT genotype modulated all
      but the motor speed measures. The Val-Met genotype was optimal for performance in
      this adolescent sample. CONCLUSIONS: Results are discussed within the context of
      developmental changes in the dopaminergic system during adolescence.

PMID- 17014829
TI  - Psychiatric disease in the twenty-first century: The case for subcortical
      ischemic depression.
AB  - The current approach to psychiatric diagnoses involves identifying symptom
      clusters that fit a specific syndrome. Although this approach has facilitated the
      field's development, advances in genetics and neuroimaging raise the question of
      how causality may fit into the diagnostic process. One approach would be a two
      axial system, wherein clinical presentation is on one axis and putative risk
      factors are on the other. This approach applies to subcortical ischemic
      depression (SID), a diagnosis corresponding to the "vascular depression"
      hypothesis. Subcortical ischemic depression affects clinical presentation, long
      term outcomes, and response to antidepressant therapy, arguing that it is a valid
      diagnostic entity worth further study.

PMID- 17014831
TI  - Direct epoxidation of D-glucal and D-galactal derivatives with in situ generated
      DMDO.
AB  - A multi-gram epoxidation of 3,4,6-tri-O-benzyl-D-glucal and D-galactal with
      dimethyldioxirane (DMDO) generated in situ from Oxone/acetone in a biphasic
      system (CH(2)Cl(2)-aqueous NaHCO(3)) resulted in the formation of the
      corresponding 1,2-anhydrosugars in a 99% yield and 100% selectivity. In a similar
      way, 3,4,6-tri-O-acetyl-D-glucal afforded a 7:1 mixture of the corresponding
      gluco and manno derivatives in an 87% overall yield.

PMID- 17014830
TI  - Effects of chloride flux modulators in an in vitro model of brain edema
      formation.
AB  - Brain edema is a serious consequence of hemispheric stroke and traumatic brain
      injury and contributes significantly to patient mortality. In the present study,
      we measured water contents in hippocampal slices as an in vitro model of edema
      formation. Excitotoxic conditions induced by N-methyl-D-aspartate (NMDA, 300
      microM), as well as ischemia induced by oxygen-glucose deprivation (OGD), caused
      cellular edema formation as indicated by an increase of slice water contents. In
      the presence of furosemide, an inhibitor of the Na,K,Cl-cotransporter, NMDA
      induced edema were reduced by 64% while OGD-induced edema were unaffected. The
      same observation, i.e., reduction of excitotoxic edema formation but no effect on
      ischemia-induced edema, was made with chloride transport inhibitors such as DIDS
      and niflumic acid. Under ischemic conditions, modulation of GABAA receptors by
      bicuculline, a GABA antagonist, or by diazepam, a GABAergic agonist, did not
      significantly affect edema formation. Further experiments demonstrated that low
      chloride conditions prevented NMDA-induced, but not OGD-induced, water influx.
      Omission of calcium ions had no effect. Our results show that NMDA-induced edema
      formation is highly dependent on chloride influx as it was prevented by low
      chloride conditions and by various compounds that interfere with chloride influx.
      In contrast, OGD-induced edema observed in brain slices was not affected by
      modulators of chloride fluxes. The results are discussed with reference to ionic
      changes occurring during tissue ischemia.

PMID- 17014832
TI  - Novel synthesis of alpha-galactosyl-ceramides and confirmation of their powerful
      NKT cell agonist activity.
AB  - alpha-Galactosyl-ceramide (1) has been identified as a powerful modulator of
      immunological processes through its capacity to bind CD1d molecules and
      specifically activate invariant natural killer (NK)-like T cells (iNKT cells).
      This paper describes the synthesis of 1, the analogous alpha-galactosyl-ceramide
      3, and its short chain analogue 'OCH' (2), by use of the 4,6-di-O-tert
      butylsilylene (DTBS) protecting group to produce a powerful alpha-galactosylating
      agent. In vivo experiments confirmed these compounds to be potent and selective
      activators of iNKT cells in a CD1d-dependent manner, each inducing a unique
      profile of cytokine release. This synthesis strategy will permit the generation
      of novel derivatives for use in the study of the mechanism of iNKT cell
      activation.

PMID- 17014833
TI  - NIS/H2SO4-Silica: a mild and efficient reagent system for the hydrolysis of
      thioglycosides.
AB  - Chemoselective hydrolysis of a variety of thioglycosides in the presence of a
      wide range of protecting groups has been achieved by using N-iodosuccinimide and
      H(2)SO(4) immobilized on silica in good to excellent yields.

PMID- 17014834
TI  - Adenosine A2A receptors are expressed in human atrial myocytes and modulate
      spontaneous sarcoplasmic reticulum calcium release.
AB  - BACKGROUND: Alterations in the cyclic AMP-dependent regulation of the cardiac
      ryanodine receptor (RyR2) have been proposed to account for increased spontaneous
      calcium release from the sarcoplasmic reticulum (SR) in patients with heart
      failure, ventricular tachyarrhythmias and atrial fibrillation. While the
      adenosine A(2A) receptor (A(2A)R) is known to regulate cyclic AMP levels,
      expression and function of this receptor in human cardiac myocytes has not been
      investigated. METHODS: PCR, western blotting and immunofluorescence were used to
      identify the A(2A)R, and functional effects of A(2A)R stimulation were measured
      with confocal calcium imaging and patch-clamp technique. RESULTS: The A(2A)R is
      expressed in the human right atrium and distributed in a banded pattern along the
      Z-lines, overlapping with the ryanodine receptor. A(2A)R stimulation caused a
      protein kinase A dependent increase in spontaneous SR calcium release in isolated
      human atrial myocytes. The A(2A)R agonist CGS21680 increased the frequency of
      calcium sparks from 0.12+/-0.03 to 0.31+/-0.08 sparks.mum min(-1) (p<0.05) and
      calcium waves from 0.65+/-0.31 to 5.11+/-1.84 waves.min(-1) (p<0.03). Moreover,
      spontaneous Na-Ca exchange currents (I(NCX)) increased from 1.19+/-0.17 to 2.50+/
      0.42 min(-1) (p<0.001). In contrast, CGS21680 did not alter caffeine inducible
      calcium release (6.98+/-0.52 vs. 6.82+/-0.57 amol pF(-1), p=0.6) or the
      spontaneous I(NCX) amplitude (0.32+/-0.05 vs. 0.29+/-0.04 pA pF(-1), p=0.2).
      Current-voltage relationship and amplitude of the L-type calcium current (1.62+/
      0.18 vs. 1.80+/-0.18 pA pF(-1)) were not altered, but calcium release dependent
      inactivation was faster with CGS21680 (13.4+/-0.7 vs. 15.8+/-1.0 ms, p<0.001).
      CONCLUSIONS: Adenosine A(2A) receptors are expressed in the human atrial
      myocardium and modulate the frequency of spontaneous calcium release from the SR.

PMID- 17014835
TI  - Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive
      genes and eNOS activity at sites of perturbed shear stress and atherogenesis.
AB  - BACKGROUND: Atherosclerosis is enhanced in arterial segments exposed to disturbed
      flow. Perturbed shear stress increases the expression of oxidation-sensitive
      responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained
      in the juice derived from the pomegranate contribute to the reduction of
      oxidative stress and atherogenesis during disturbed shear stress. AIM OF THE
      STUDY: To evaluate the effects of intervention with the Pomegranate Fruit Extract
      (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p
      CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high
      shear stress in vitro and in vivo. RESULTS: At the doses used in the study, both
      the PFE and the regular pomegranate juice concentrate reduced the activation of
      ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed
      shear stress) in cultured human endothelial cells and in atherosclerosis-prone
      areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic
      GMP levels while there was no significant effect of both compounds on the
      conversion of L-arginine to L-citrulline. Administration of these compounds to
      hypercholesterolemic mice significantly reduced the progression of
      atherosclerosis and isoprostane levels and increased nitrates. This protective
      effect was relevant with PFE. Vasomotor reactivity was improved and EC(25) values
      in response to Ach and NONOate were significantly increased in treated mice in
      comparison to controls. CONCLUSION: This study indicates that the proatherogenic
      effects induced by perturbed shear stress can be also reversed by chronic
      administration of PFE.

PMID- 17014836
TI  - Rapid molecular characterization of Hb Queens and Hb Siam: two variants easily
      misidentified as sickle Hb.
AB  - OBJECTIVE: To establish a rapid differential diagnosis of hemoglobin (Hb) Queens
      and Hb Siam from other clinically relevant variants. DESIGN AND METHODS:
      Molecular and hematological features associated with two pregnant Thai women who
      were mistaken for Hb S were investigated. A simultaneous DNA diagnosis based on
      multiplex allele specific PCR approach was developed and tested with other common
      variants. RESULTS: Apart from mild anemia, the two subjects were generally
      healthy. DNA analysis identified that they were respectively carriers of Hb Siam
      [alpha15(A13)Gly-Arg] and Hb Queens [alpha34(B15)Leu-Arg]. A successful
      application of the multiplex allele specific PCR for differential diagnosis was
      demonstrated. CONCLUSION: Diagnosis of these clinically relevant
      hemoglobinopathies is problematic in the routine setting, and the method
      developed should prove useful in complementing routine Hb analysis for providing
      accurate diagnosis.

PMID- 17014837
TI  - Increase diagnostic efficacy by combined use of fingerprint markers in mass
      spectrometry--plasma peptidomes from nasopharyngeal cancer patients for example.
AB  - OBJECTIVES: There is no plasma marker for detecting nasopharyngeal cancer (NPC).
      We developed a bead-based affinity fractionated proteomic method to search
      potential plasma markers for NPC. DESIGN AND METHODS: Affinity purification of
      heparinized plasma with Cu-chelated beads and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis
      were used to screen potential NPC markers. We compiled MS protein profiles for 47
      patients with NPC and compared them to profiles from 28 healthy controls. The
      spectra were statistically analyzed using flexAnalysis and ClinProt
      bioinformatics software. Diagnostic efficacy was evaluated by determination of
      the assay sensitivity and specificity of each marker. RESULTS: Twelve mass
      fingerprint markers differing between cancer and control spectra were found. The
      sensitivities of these NPC markers are various ranging from 36% to 83%, and the
      specificities were all over 90%. Combine use of these markers significantly
      increases diagnostic efficacy. In which, the combined markers (2020 Da and 4635
      Da) possess best discriminator with high sensitivity (94%) and specificity (93%).
      We further identify a C3 fragment, C3f, that may serve as a biomarker for NPC.
      CONCLUSION: The combined use of mass fingerprint markers in plasma proteome will
      enhance diagnostic efficacy for NPC. This method can be applied to search for
      novel plasma markers for cancers.

PMID- 17014838
TI  - Lineage-specific expansions provide genomic complexity among sea urchin GTPases.
AB  - In every organism, GTP-binding proteins control many aspects of cell signaling.
      Here, we examine in silico several GTPase families from the Strongylocentrotus
      purpuratus genome: the monomeric Ras superfamily, the heterotrimeric G proteins,
      the dynamin superfamily, the SRP/SR family, and the "protein biosynthesis"
      translational GTPases. Identified were 174 GTPases, of which over 90% are
      expressed in the embryo as shown by tiling array and expressed sequence tag data.
      Phylogenomic comparisons restricted to Drosophila, Ciona, and humans
      (protostomes, urochordates, and vertebrates, respectively) revealed both common
      and unique elements in the expected composition of these families. Galpha and
      dynamin families contain vertebrate expansions, consistent with whole genome
      duplications, whereas SRP/SR and translational GTPases are highly conserved.
      Unexpectedly, Ras superfamily analyses revealed several large (5+) lineage
      specific expansions in the sea urchin. For Rho, Rab, Arf, and Ras subfamilies,
      comparing total human gene numbers to the number of sea urchin genes with
      vertebrate orthologs suggests reduced genomic complexity in the sea urchin.
      However, gene duplications in the sea urchin increase overall numbers such that
      total sea urchin gene numbers approximate vertebrate gene numbers for each
      monomeric GTPase family. These findings suggest that lineage-specific expansions
      may be an important component of genomic evolution in signal transduction.

PMID- 17014840
TI  - N-cadherin is required for neural crest remodeling of the cardiac outflow tract.
AB  - Cardiac neural crest cells undergo extensive cell rearrangements during the
      formation of the aorticopulmonary septum in the outflow tract. However, the
      morphogenetic mechanisms involved in this fundamental process remain poorly
      understood. To determine the function of the Ca2+-dependent cell adhesion
      molecule, N-cadherin, in murine neural crest, we applied the Cre/loxP system and
      created mouse embryos genetically mosaic for N-cadherin. Specifically, deletion
      of N-cadherin in neural crest cells led to embryonic lethality with distinct
      cardiovascular defects. Neural crest cell migration and homing to the cardiac
      outflow tract niche were unaffected by loss of N-cadherin. However, N-cadherin
      deficient neural crest cells were unable to undergo the normal morphogenetic
      changes associated with outflow tract remodeling, resulting in persistent truncus
      arteriosus in the majority of mutant embryos. Other mutant embryos initiated
      aorticopulmonary septum formation; however, the neural crest cells were unable to
      elongate and align properly along the midline and remained rounded with limited
      contact with their neighbors. Interestingly, rotation of the outflow tract was
      incomplete in these mutants suggesting that alignment of the channels is
      dependent on N-cadherin-generated cytoskeletal forces. A second cardiac phenotype
      was observed where loss of N-cadherin in the epicardium led to disruption of
      heterotypic cell interactions between the epicardium and myocardium resulting in
      a thinned ventricular myocardium. Thus, we conclude that in addition to its role
      in myocardial cell adhesion, N-cadherin is required for neural crest cell
      rearrangements critical for patterning of the cardiac outflow tract and in the
      maintenance of epicardial-myocardial cell interactions.

PMID- 17014839
TI  - Long-range downstream enhancers are essential for Pax6 expression.
AB  - Pax6 is a developmental control gene with an essential role in development of the
      eye, brain and pancreas. Pax6, as many other developmental regulators, depends on
      a substantial number of cis-regulatory elements in addition to its promoters for
      correct spatiotemporal and quantitative expression. Here we report on our
      analysis of a set of mice transgenic for a modified yeast artificial chromosome
      carrying the human PAX6 locus. In this 420 kb YAC a tauGFP-IRES-Neomycin reporter
      cassette has been inserted into the PAX6 translational start site in exon 4. The
      YAC has been further engineered to insert LoxP sites flanking a 35 kb long,
      distant downstream regulatory region (DRR) containing previously described DNaseI
      hypersensitive sites, to allow direct comparison between the presence or absence
      of this region in the same genomic context. Five independent transgenic lines
      were obtained that vary in the extent of downstream PAX6 locus that has
      integrated. Analysis of transgenic embryos carrying full-length and truncated
      versions of the YAC indicates the location and putative function of several novel
      tissue-specific enhancers. Absence of these distal regulatory elements abolishes
      expression in specific tissues despite the presence of more proximal enhancers
      with overlapping specificity, strongly suggesting interaction between these
      control elements. Using plasmid-based reporter transgenic analysis we provide
      detailed characterization of one of these enhancers in isolation. Furthermore, we
      show that overexpression of a short PAX6 isoform derived from an internal
      promoter in a multicopy YAC transgenic line results in a microphthalmia
      phenotype. Finally, direct comparison of a single-copy line with the floxed DRR
      before and after Cre-mediated deletion demonstrates unequivocally the essential
      role of these long-range control elements for PAX6 expression.

PMID- 17014841
TI  - FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular
      invasion of the growth plate.
AB  - Fibroblast growth factor 18 (FGF18) has been shown to regulate chondrocyte
      proliferation and differentiation by signaling through FGF receptor 3 (FGFR3) and
      to regulate osteogenesis by signaling through other FGFRs. Fgf18(-/-) mice have
      an apparent delay in skeletal mineralization that is not seen in Fgfr3(-/-) mice.
      However, this delay in mineralization could not be simply explained by FGF18
      signaling to osteoblasts. Here we show that delayed mineralization in Fgf18(-/-)
      mice was closely associated with delayed initiation of chondrocyte hypertrophy,
      decreased proliferation at early stages of chondrogenesis, delayed skeletal
      vascularization and delayed osteoclast and osteoblast recruitment to the growth
      plate. We further show that FGF18 is necessary for Vegf expression in
      hypertrophic chondrocytes and the perichondrium and is sufficient to induce Vegf
      expression in skeletal explants. These findings support a model in which FGF18
      regulates skeletal vascularization and subsequent recruitment of
      osteoblasts/osteoclasts through regulation of early stages of chondrogenesis and
      VEGF expression. FGF18 thus coordinates neovascularization of the growth plate
      with chondrocyte and osteoblast growth and differentiation.

PMID- 17014842
TI  - Growth control in the proliferative region of the Drosophila eye-head primordium:
      the elbow-noc gene complex.
AB  - Notch signaling is involved in cell differentiation and patterning, as well as in
      the regulation of growth and cell survival. Notch activation at the dorsal
      ventral boundary of the Drosophila eye-head primordium leads to the expression of
      the secreted protein Unpaired, a ligand of the JAK-STAT pathway that induces cell
      proliferation in the undifferentiated tissue. The zinc finger proteins encoded by
      elbow and no ocelli are expressed in the highly proliferative region of the eye
      head primordium. Loss of elbow and no ocelli activities induces overgrowths of
      the head capsule, without inducing Upd expression de novo. These overgrowths
      depend on Notch activity suggesting that elbow and noc repress a Upd independent
      role of Notch in driving cell proliferation. When the size of the overgrown
      tissue is increased, ectopic antenna and eye structures can be found. Thus, tight
      regulation of the size of the eye-head primordium by elbow and no ocelli is
      crucial for proper fate specification and generation of the adult structures.

PMID- 17014843
TI  - DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and
      acts as a repressor of gene transcription.
AB  - DIPA (delta-interacting protein A) was initially identified as a protein that
      associates with the hepatitis delta antigen. In this study, we found that DIPA
      can associate with p78/MCRS/MSP58, a Forkhead-associated domain containing
      protein implicated in malignant transformation as well as in regulation of gene
      transcription and translation. We analyzed the interaction between DIPA and p78
      by co-immunoprecipitation and identified the structural regions involved in the
      interaction. Consistent with the physical interaction, we found that DIPA is
      predominant co-localized with p78 to the nucleus. In addition, a fraction of DIPA
      can be detected on the centrosome. Furthermore, we demonstrate that DIPA can act
      as a repressor of gene transcription, an activity that appears to be enhanced by
      p78. Taken together, our results revealed a novel protein complex that plays a
      role in regulation of gene expression and cell proliferation. We propose that
      dysfunction of DIPA may contribute to malignant transformation by affecting the
      functions of p78.

PMID- 17014844
TI  - MyoD undergoes a distinct G2/M-specific regulation in muscle cells.
AB  - The transcription factors MyoD and Myf5 present distinct patterns of expression
      during cell cycle progression and development. In contrast to the mitosis
      specific disappearance of Myf5, which requires a D-box-like motif overlapping the
      basic domain, here we describe a stable and inactive mitotic form of MyoD
      phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In
      mitosis, these modifications are required for releasing MyoD from condensed
      chromosomes and inhibiting its DNA-binding and transcriptional activation
      ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due
      to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A
      is not excluded from condensed chromatin and alters mitotic progression with
      apparent abnormalities. Thus, the drop of MyoD below a threshold level and its
      displacement from the mitotic chromatin could present another window in the cell
      cycle for resetting the myogenic transcriptional program and to maintain the
      myogenic determination of the proliferating cells.

PMID- 17014845
TI  - Caveolin-1 up-regulates IGF-I receptor gene transcription in breast cancer cells
      via Sp1- and p53-dependent pathways.
AB  - The insulin-like growth factor (IGF) system plays an important role in the
      biology of breast cancer. Most of the biological actions of IGF-I and IGF-II are
      mediated by the IGF-I receptor (IGF-IR), a membrane-bound heterotetramer with
      potent antiapoptotic and cell survival activities. Caveolin-1 (Cav-1) is one of
      the main components of caveolae, and it has been shown to interact with multiple
      signaling molecules. In view of the important roles of IGF-IR and Cav-1 in
      oncogenically transformed mammary gland cells, in the present study we addressed
      the potential regulation of IGF-IR gene expression by Cav-1. The results obtained
      showed that MCF7/Cav-1 cells, expressing the Cav-1 gene in a stable manner,
      contain significantly higher levels of IGF-IR protein and mRNA than native MCF7
      cells. These elevated levels of expression are mediated at the level of
      transcription, as shown by the results of experiments showing that the activity
      of the proximal IGF-IR promoter was higher in Cav-1-expressing MCF7 cells than in
      untransfected MCF7 cells. Furthermore, in subcellular localization studies,
      intensive IGF-IR staining in membrane ruffles and projections in MCF7/Cav-1 cells
      were noted, in contrast to typical membrane staining in MCF7 cells. In addition,
      we demonstrated that transcriptional activation of the IGF-IR gene by Cav-1
      requires an intact p53 signaling pathway, since Cav-1 was unable to elevate IGF
      IR levels in p53-null cells. Finally, the effect of Cav-1 was associated with an
      elevation in the levels of Sp1, a zinc-finger protein with important roles in IGF
      IR gene transactivation. In summary, we identified the IGF-IR gene as a
      downstream target for Cav-1 action in breast cancer cells.

PMID- 17014846
TI  - Axon regeneration through scars and into sites of chronic spinal cord injury.
AB  - Cellular and extracellular inhibitors are thought to restrict axon growth after
      chronic spinal cord injury (SCI), confronting the axon with a combination of
      chronic astrocytosis and extracellular matrix-associated inhibitors that
      collectively constitute the chronic "scar." To examine whether the chronically
      injured environment is strongly inhibitory to axonal regeneration, we grafted
      permissive autologous bone marrow stromal cells (MSCs) into mid-cervical SCI
      sites of adult rats, 6 weeks post-injury without resection of the "chronic scar."
      Additional subjects received MSCs genetically modified to express neurotrophin-3
      (NT-3), providing a further local stimulus to axon growth. Anatomical analysis 3
      months post-injury revealed extensive astrocytosis surrounding the lesion site,
      together with dense deposition of the inhibitory extracellular matrix molecule
      NG2. Despite this inhibitory environment, axons penetrated the lesion site
      through the chronic scar. Robust axonal regeneration occurred into chronic lesion
      cavities expressing NT-3. Notably, chronically regenerating axons preferentially
      associated with Schwann cell surfaces expressing both inhibitory NG2 substrates
      and the permissive substrates L1 and NCAM in the lesion site. Collectively, these
      findings indicate that inhibitory factors deposited at sites of chronic SCI do
      not create impenetrable boundaries and that inhibition can be balanced by local
      and diffusible signals to generate robust axonal growth even without resecting
      chronic scar tissue.

PMID- 17014847
TI  - Brain neuroprotection by scavenging blood glutamate.
AB  - Excess glutamate in brain fluids characterizes acute brain insults such as
      traumatic brain injury and stroke. Its removal could prevent the glutamate
      excitotoxicity that causes long-lasting neurological deficits. As blood glutamate
      scavenging has been demonstrated to increase the efflux of excess glutamate from
      brain into blood, we tested the prediction that oxaloacetate-mediated blood
      glutamate scavenging causes neuroprotection in a pathological situation such as
      closed head injury (CHI), in which there is a well established deleterious
      increase of glutamate in brain fluids. We observed highly significant
      improvements of the neurological status of rats submitted to CHI following an
      intravenous treatment with 1 mmol oxaloacetate/100 g rat weight which decreases
      blood glutamate levels by 40%. No detectable therapeutic effect was obtained when
      rats were treated IV with 1 mmol oxaloacetate together with 1 mmol glutamate/100
      g rat. The treatment with 0.005 mmol/100 g rat oxaloacetate was no more effective
      than saline but when it was combined with the intravenous administration of 0.14
      nmol/100 g of recombinant glutamate-oxaloacetate transaminase, recovery was
      almost complete. Oxaloacetate provided neuroprotection when administered before
      CHI or at 60 min post CHI but not at 120 min post CHI. Since neurological
      recovery from CHI was highly correlated with the decrease of blood glutamate
      levels (r=0.89, P=0.001), we conclude that blood glutamate scavenging affords
      brain neuroprotection Blood glutamate scavenging may open now new therapeutic
      options.

PMID- 17014848
TI  - NR2B-containing NMDA receptor is required for morphine-but not stress-induced
      reinstatement.
AB  - Glutamate receptors are known to be densely distributed in the forebrain
      rewarding circuits, and glutamatergic transmission is actively involved in the
      regulation of rewarding and reinstating effects of drugs of abuse. Here we
      investigated the possible involvement of the N-methyl-D-aspartate (NMDA)
      receptors in the reinstatement of extinguished morphine conditioned place
      preference (CPP) in rats. We found that previously extinguished morphine (3
      mg/kg, i.p.) CPP was markedly reinstated by a priming injection of morphine (2
      mg/kg, i.p.) or an acute environmental stressor (forced swim for 10 min), but not
      by the stress induced by a 24-h food deprivation. Parallel with this, protein
      levels of the NMDA receptor 2B subunit (NR2B) were elevated in the nucleus
      accumbens (NAc) and the hippocampus, but not the prefrontal cortex, of reinstated
      rats. Systemic administration of an NR2B selective antagonist ifenprodil (1, 3,
      10 mg/kg, i.p.) attenuated the reinstatement induced by a priming morphine
      injection, although not by the forced swim. Ifenprodil (2.0 microg/rat) directly
      injected into the NAc shell or the CA1 region of the dorsal hippocampus produced
      a similar effect. These results indicate that the NR2B-containing NMDA receptors
      in the NAc and the dorsal hippocampus play a significant role in mediating the
      reinstatement of rewarding responses to morphine.

PMID- 17014849
TI  - Identification of a tryptophan-like epitope borne by the variable surface
      glycoprotein (VSG) of African trypanosomes.
AB  - Antibodies (Ab) directed against a tryptophan-like epitope (WE) were previously
      detected in patients with human African trypanosomiasis (HAT). We investigated
      whether or not these Ab resulted from immunization against trypanosome antigen(s)
      expressing a WE. By Western blotting, we identified an antigen having an apparent
      molecular weight ranging from 60 to 65 kDa, recognized by purified rabbit anti-WE
      Ab. This antigen, present in trypomastigote forms, was absent in procyclic forms
      and Trypanosoma cruzi trypomastigotes. Using purified variable surface
      glycoproteins (VSG) from various trypanosomes, we showed that VSG was the
      parasite antigen recognized by these rabbit Ab. Anti-WE and anti-VSG Ab were
      purified from HAT sera by affinity chromatography. Immunoreactivity of purified
      antibodies eluted from affinity columns and of depleted fractions showed that WE
      was one of the epitopes borne by VSG. These data underline the existence of an
      invariant WE in the structure of VSG from several species of African
      trypanosomes.

PMID- 17014850
TI  - Tritrichomonas foetus: pathogenesis of acute infection in normal, estradiol
      treated, and stressed mice.
AB  - Environmental stress and endocrine control can affect pathogenesis of sexually
      transmitted diseases such as trichomoniasis. Acute Tritrichomonas foetus
      infection was compared in female BALB/c mice to infections in mice treated with
      high doses of estradiol or housed in constant bright illumination (stressed). In
      untreated mice, T. foetus readily colonized the reproductive tract, causing
      minimal epithelial damage and inflammation. Several fold increases of IFN-gamma,
      TNF-alpha, MCP-1, and IL-6 cytokines were detected after estradiol-treatment of
      mice, resulting in greatly enhanced inflammation and tissue damage throughout the
      reproductive tract. Interestingly, estradiol-treatment of mice resulted in
      reduced T. foetus colonization compared to untreated mice. Infection in stressed
      mice resulted in increased tissue damage, inflammation, and inflammatory cytokine
      expression, although parasite colonization within the reproductive tract was
      similar to that in untreated mice. These results indicate that either estradiol
      treatment or stress result in pathogenesis often observed during severe disease.
      Alternatively, infection in non-treated mice results in chronic colonization,
      with little inflammation or pathology.

PMID- 17014851
TI  - Mapping of two O-GlcNAc modification sites in the capsid protein of the potyvirus
      Plum pox virus.
AB  - A large number of O-linked N-acetylglucosamine (O-GlcNAc) residues have been
      mapped in vertebrate proteins, however targets of O-GlcNAcylation in plants still
      have not been characterized. We show here that O-GlcNAcylation of the N-terminal
      region of the capsid protein of Plum pox virus resembles that of animal proteins
      in introducing O-GlcNAc monomers. Thr-19 and Thr-24 were specifically O
      GlcNAcylated. These residues are surrounded by amino acids typical of animal O
      GlcNAc acceptor sites, suggesting that the specificity of O-GlcNAc transferases
      is conserved among plants and animals. In laboratory conditions, mutations
      preventing O-GlcNAcylation of Thr-19 and Thr-24 did not have noticeable effects
      on PPV competence to infect Prunus persicae or Nicotiana clevelandii. However,
      the fact that Thr-19 and Thr-24 are highly conserved among different PPV strains
      suggests that their O-GlcNAc modification could be relevant for efficient
      competitiveness in natural conditions.

PMID- 17014852
TI  - Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent
      pathway.
AB  - Klotho has recently emerged as a regulator of aging. To investigate the role of
      Klotho in the regulation of cellular senescence, we generated stable MRC-5 human
      primary fibroblast cells knockdown for Klotho expression by RNAi. Downregulation
      of Klotho dramatically induces premature senescence with a concomitant
      upregulation of p21. The upregulation of p21 is associated with cell cycle arrest
      at G1/S boundary. Knockdown of p53 in the Klotho attenuated MRC-5 cells restores
      normal growth and replicative potential. These results demonstrate that Klotho
      normally regulates cellular senescence by repressing the p53/p21 pathway. Our
      findings implicate Klotho as a regulator of aging in primary human fibroblasts.

PMID- 17014853
TI  - A biphasic viscohyperelastic fibril-reinforced model for articular cartilage:
      formulation and comparison with experimental data.
AB  - Experiments in articular cartilage have shown highly nonlinear stress-strain
      curves under finite deformations, nonlinear tension-compression response as well
      as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers.
      A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is
      able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar
      components of the solid phase, the nonlinear tension-compression response and the
      nonlinear stress-strain curves under tension and compression. A viscohyperelastic
      constitutive equation was used for the matrix and the fibers encompassing,
      respectively, a hyperelastic function used previously for the matrix and a
      hyperelastic law used before to represent biological connective tissues. This
      model, implemented in an updated Lagrangian finite element code, displayed good
      ability to follow experimental stress-strain equilibrium curves under tension and
      compression for human humeral cartilage. In addition, curve fitting of
      experimental reaction force and lateral displacement unconfined compression
      curves showed that the inclusion of viscous effects in the matrix allows the
      description of experimental data with material properties for the fibers
      consistent with experimental tensile tests, suggesting that intrinsic viscous
      effects in the matrix of articular cartilage plays an important role in the
      mechanical response of the tissue.

PMID- 17014854
TI  - Meniscal wear at a three-component total ankle prosthesis by a knee joint
      simulator.
AB  - Despite the fundamental value of wear simulation studies to assess wear
      resistance of total joint replacements, neither specialised simulators nor
      established external conditions are available for the human ankle joint. The aim
      of the present study was to verify the suitability of a knee wear simulator to
      assess wear rates in ankle prostheses, and to report preliminary this rate for a
      novel three-component total ankle replacement design. Four intact 'small' size
      specimens of the Box ankle were analysed in a four-station knee wear simulator.
      Special component-to-actuator holders were manufactured and starting spatial
      alignment of the three-components was sought. Consistent load and motion cycles
      representing conditions at the ankle joint replaced exactly with the prosthesis
      design under analysis were taken from a corresponding mechanical model of the
      stance phase of walking. The weight loss for the three specimens, after two
      million cycles, was 32.68, 14.78, and 62.28mg which correspond to a linear
      penetration of 0.018, 0.008, and 0.034mm per million-cycle, respectively for the
      specimens #1, #2, and #3. The knee wear simulator was able to reproduce load
      motion patterns typical of a replaced ankle. Motion of the meniscal bearing in
      between the tibial and talar components was smooth, this component remaining in
      place and in complete congruence with the metal components throughout the test.

PMID- 17014855
TI  - Determination of erythromycin and related substances in commercial samples using
      liquid chromatography/ion trap mass spectrometry.
AB  - A sensitive, precise and accurate quantitative liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) method for the measurement of erythromycin A (EA) and
      related substances in commercial samples was developed and validated. The samples
      were chromatographed on a reversed-phase column with a polar endcapping and
      analyzed by ion trap tandem mass spectrometry in the multiple reaction monitoring
      (MRM) mode using positive electrospray ionization. The method showed high
      recovery (>or=98.82%), high sensitivity (lower limit of quantitation of 0.25
      ng/mL for EA and less than 7.3 ng/mL for the related substances) and high
      precision (<or=0.52%) as well as excellent linearity (r(2)>or=0.991) with a run
      time of only 13 min. The method was successfully applied to the determination of
      EA and related substances in commercial samples. Moreover, using the advanced
      data-dependent acquisition capability of the ion trap software two new unexpected
      EA related substances could be detected and possible structures for these
      substances were postulated.

PMID- 17014856
TI  - Role of zwitterionic structures in the solid-phase extraction based method
      development for clean up of tetracycline and oxytetracycline from honey.
AB  - Solid-phase extraction (SPE) based sample clean up of tetracycline (TC) and
      oxytetracycline (OTC) from honey samples was evaluated using a neutral polymeric
      sorbent (strata-X), a weak cation exchange polymeric sorbent (strata-X-CW) and a
      combination of neutral and strong cation exchange sorbents (strata-X plus Strata
      Screen-C or strata-X-C). Both TC and OTC are recovered in low yields from the
      strong cation exchange sorbents strata-X-C and Strata-Screen-C under basic (pH
      >9) or acidic (pH >or=2) elution conditions. The cleanest extracts along with
      quantitative recoveries were obtained with strata-X-CW under either acidic or
      basic elution conditions, as demonstrated by analysis of eluates by both LC/UV
      and LC/MS-MS. On the other hand, the neutral sorbent (strata-X) was less
      efficient in eliminating the honey matrix constituents, since it could not retain
      the tetracyclines with the strong organic wash needed to remove other compounds.
      The differences in the elution behavior of the strong and weak cation exchange
      sorbents is rationalized on the basis of divergent deprotonation mechanisms of
      the tetracyclines, which exist in the zwitterionic structures under the SPE
      conditions.

PMID- 17014857
TI  - Investigating noncovalent squarylium dye-protein interactions by capillary
      electrophoresis-frontal analysis.
AB  - Noncovalent interactions between fluorescent probe molecules and protein analyte
      molecules, which typically occur with great speed and minimal sample handling,
      form the basis of many high sensitivity analytical techniques. Understanding the
      nature of these interactions and the composition of the resulting complexes
      represents an important area of study that can be facilitated by capillary
      electrophoresis (CE). Specifically, we will present how frontal analysis (FA) and
      Hummel-Dreyer (HD) methods can be implemented with CE to determine association
      constants and stoichiometries of noncovalent complexes of the red luminescent
      squarylium dye Red-1c with bovine serum albumin (BSA) and beta-lactoglobulin A.
      By adjusting solution conditions, such as pH or ionic strength, it is possible to
      selectively modify the binding process. As such, conditions for optimal
      selectivity for labeling reactions can be established by capillary
      electrophoresis-frontal analysis (CE-FA) investigations.

PMID- 17014858
TI  - Analysis of 2-aminoacetophenone in wine using a stable isotope dilution assay and
      multidimensional gas chromatography-mass spectrometry.
AB  - The key compound in the wine off-flavor phenomenon "Untypische Alterungsnote"
      (UTA) is 2-aminoacetophenone (AAP). A new method for its quantitative analysis in
      wine is described. The analysis is based on solid phase extraction with LiChrolut
      EN as sorbent material followed by multidimensional gas chromatography coupled to
      mass spectrometry (MDGC-MS). Matrix effects due to the complex wine aroma
      composition could be overcome by an alkaline washing step of the extract and the
      use of selected ion monitoring as detection mode. Quantification is based on a
      stable isotope dilution assay using deuterated 2-aminoacetophenone as internal
      standard.

PMID- 17014859
TI  - Supercooled liquid vapour pressures and related thermodynamic properties of
      polycyclic aromatic hydrocarbons determined by gas chromatography.
AB  - A gas chromatographic method using Kovats retention indices has been applied to
      determine the liquid vapour pressure (P(i)), enthalpy of vaporization (DeltaH(i))
      and difference in heat capacity between gas and liquid phase (DeltaC(i)) for a
      group of polycyclic aromatic hydrocarbons (PAHs). This group consists of 19
      unsubstituted, methylated and sulphur containing PAHs. Differences in log P(i) of
      -0.04 to +0.99 log units at 298.15K were observed between experimental values and
      data from effusion and gas saturation studies. These differences in log P(i) have
      been fitted with multilinear regression resulting in a compound and temperature
      dependent correction. Over a temperature range from 273.15 to 423.15K,
      differences in corrected log P(i) of a training set (-0.07 to +0.03 log units)
      and a validation set (-0.17 to 0.19 log units) were within calculated error
      ranges. The corrected vapour pressures also showed a good agreement with other GC
      determined vapour pressures (average -0.09 log units).

PMID- 17014860
TI  - Use of inverse gas chromatography to account for the pervaporation performance in
      monitoring the oxidation of primary alcohols.
AB  - The oxidation of n-propanol and n-butanol to their corresponding aldehydes was
      monitored by the pervaporation technique. Mass transfer phenomenon that occurs in
      the pervaporation process was confirmed by the results of inverse gas
      chromatography. Polydimethylsiloxane (PDMS), a hydrophobic polymer widely
      employed as a membrane in pervaporation technique, was evaluated as a stationary
      phase in this study. The retention times of the different molecules probes (n
      propanol, n-butanol, propionaldehyde, and butyraldehyde), molecules involved as
      reactants and products in the oxidation reaction, gave an insight into the extent
      of the interactions between each of these molecules and the stationary phase. The
      infinite dilution conditions allowed to measure the infinite dilution activity
      coefficient, gamma(infinity), and the specific retention volume, V(g)(0), and to
      estimate the Flory-Huggins parameter interactions, chi(12)(infinity). The
      magnitudes of these parameters threw some light on the permselectivity of the
      membranes in the pervaporation operation.

PMID- 17014861
TI  - Analysis of hexabromocyclododecane diastereomers and enantiomers by liquid
      chromatography/tandem mass spectrometry: chromatographic selectivity and
      ionization matrix effects.
AB  - Hexabromocyclododecane (HBCD) is a flame retardant that is undergoing
      environmental risk assessment. The liquid chromatographic retention and
      electrospray ionization matrix effects were investigated for HBCD methods of
      analysis for environmental matrices. Column selectivity towards HBCD
      diastereomers was evaluated for C30 and C18 stationary phases under different
      mobile phase conditions and column temperatures. The HBCD elution order was
      dependent on the shape selectivity of the stationary phase and the mobile phase
      composition. Greater resolution, on columns with reduced shape selectivity, of
      beta-HBCD and gamma-HBCD was achieved with the use of an acetonitrile/water
      (compared with a methanol/water) mobile phase composition. A liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)
      method for the analysis of HBCD in biological tissues was evaluated for potential
      matrix effects. The influence of extracted matrix components on HBCD diastereomer
      and enantiomer analysis was investigated using a postextraction addition
      approach. Although the analysis of HBCD diastereomers was relatively unaffected
      by the sample matrix, the responses of the HBCD enantiomers in tissue samples
      were significantly influenced by matrix effects and other changes to the
      ionization conditions. The use of racemic 13C-labeled HBCD diastereomers as
      internal standards for enantiomer fraction measurements corrected for the changes
      in the mass spectrometer response.

PMID- 17014862
TI  - Synthesis of a molecularly imprinted polymer for the selective solid-phase
      extraction of chloramphenicol from honey.
AB  - Solid-phase extraction (SPE) with a molecularly imprinted polymer (MIP) as
      sorbent has been investigated for the clean-up of the broad-spectrum
      bacteriostatic antibiotic chloramphenicol (CAP) in honey samples. The MIP was
      prepared by using methacrylic acid (MAA) as functional monomer, ethylene glycol
      dimethacrylate (EDMA) as cross-linker, chloroform as porogen and CAP as template
      molecule. The binding behaviour of the template CAP on the MIP was evaluated by
      high-performance liquid chromatography, and then the MIP was applied as a sorbent
      in SPE to selectively extract CAP from honey. It was shown that recoveries of
      nearly 100% of a CAP standard solution and up to 94% from spiked honey samples
      could be obtained after SPE.

PMID- 17014863
TI  - What do we learn from double Cx40/Cx45-deficient mice about cardiac morphogenetic
      defects and conduction abnormalities?

PMID- 17014864
TI  - Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from
      normotensive and spontaneously hypertensive rats.
AB  - Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal
      cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent
      observations indicate that CT-1 may be involved in pressure overload left
      ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects
      of CT-1 are different in cardiomyocytes isolated from adult normotensive and
      spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry
      and confocal microscopy, contractile proteins were quantified by Western blotting
      and real-time RT-PCR, and intracellular pathways were analyzed with specific
      chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell
      area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1
      augmented cell length (p<0.01) but did not modify either the transverse diameter
      or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width
      (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC
      2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation
      (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two
      cell types. All distinct effects observed in cardiomyocytes from SHR were
      mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells,
      and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in
      cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade
      inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo
      determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA
      and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared
      with pre-hypertensive SHR. These findings reveal a specific cell-broadening
      effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive
      phenotype of these cells may influence the hypertrophic effects of CT-1, probably
      by means of an exaggerated induction of angiotensinogen expression. We suggest
      that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with
      the renin-angiotensin system.

PMID- 17014865
TI  - Formation, characterization and partial purification of a Tn5 strand transfer
      complex.
AB  - DNA transposition reactions typically involve a strand transfer step wherein the
      transposon ends are covalently joined by the transposase protein to a short
      target site. There is very little known about the transposase-DNA interactions
      that direct this process, and thus our overall understanding of the dynamics of
      DNA transposition reactions is limited. Tn5 presents an attractive system for
      defining such interactions because it has been possible to solve the structure of
      at least one Tn5 transposition intermediate: a transpososome formed with pre
      cleaved ends. However, insertion specificity in the Tn5 system is low and this
      has hampered progress in generating target-containing transpososomes that are
      homogeneous in structure (i.e. where a single target site is engaged) and
      therefore suitable for biochemical and structural analysis. We have developed a
      system where the Tn5 transpososome integrates almost exclusively into a single
      target site within a short DNA fragment. The key to establishing this high degree
      of insertion specificity was to use a target DNA with tandem repeats of a
      previously characterized Tn5 insertion hotspot. The target DNA requirements to
      form this strand transfer complex are evaluated. In addition, we show that target
      DNAs missing single phosphate groups at specific positions are better substrates
      for strand transfer complex formation relative to the corresponding unmodified
      DNA fragments. Moreover, utilization of missing phosphate substrates can increase
      the degree of target site selection. A method for concentrating and partially
      purifying the Tn5 strand transfer complex is described.

PMID- 17014866
TI  - Self-assessment of functional status in schizophrenia.
AB  - With new treatments targeting features of schizophrenia associated with
      functional disability, there is a need to evaluate the validity of ratings of
      everyday outcomes. It is unknown whether patients can validly self-report on
      aspects of their functional status, which would be a potentially economical
      method for obtaining outcome data. In this study, 67 older schizophrenia
      outpatients provided self-ratings of everyday real-world functioning using the
      specific levels of functioning scale (SLOF). They were also administered
      assessments of neuropsychological performance, performance-based measures of
      functional capacity and social skills, clinical symptoms, and quality of life.
      Case managers, unaware of other ratings, also generated SLOF ratings. Based on
      discrepancy scores, participants were categorized as accurate raters (n=24),
      underestimators (n=16), or overestimators (n=27) of their functional status as
      compared to case managers' ratings. Patients' self-rated functional status was
      correlated with their subjective quality of life, but remarkably unassociated
      with case manager ratings of functional status or their own performance on
      functional capacity or social skills measures. Case manager ratings, however,
      were highly correlated with performance on functional capacity and social skills
      measures. Patients who underestimated their real world performance had better
      cognitive skills and greater self-rated depression than those who overestimated.
      Accurate raters demonstrated greater social skills than both overestimators and
      underestimators, while overestimators were most cognitively and functionally
      impaired. Accurate ratings of everyday outcomes in schizophrenia may require
      systematic observation of real world outcomes or performance-based measures, as
      self-reports were inconsistent with objective information.

PMID- 17014867
TI  - Characterization of cardiomyocyte excitation-contraction coupling in the FVB/N
      C57BL/6 intercrossed "chocolate" brown mice.
AB  - Mice are extensively used for gene modification research and isolated
      cardiomyocytes are essential for evaluation of cardiac function without
      interference from non-myocyte contribution. This study was designed to
      characterize cardiomyocyte excitation-contraction coupling in FVB/N-C57BL/6
      intercrossed brown mice. Mechanical and intracellular Ca(2+) properties were
      evaluated using an IonOptix softedge system including peak shortening (PS), time
      to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening
      and relengthening (+/- dL/dt), intracellular Ca(2+) rise and decay rate. Resting
      cell length was longer in age- and gender-matched C57BL/6 and brown mice compared
      to FVB strain. PS and +/- dL/dt were significantly lower in brown mice compared
      to FVB/N and C57BL/6 groups. TPS was shortened in C57BL/6 mice and TR(90) was
      prolonged in brown mice compared to other groups. Resting intracellular Ca(2+)
      level and single exponential intracellular Ca(2+) decay constant were comparable
      among all three mouse lines. Rise in intracellular Ca(2+) in response to
      electrical stimulus was higher in C57BL/6 mouse myocytes whereas bi-exponential
      intracellular Ca(2+) decay was faster in brown mice. Myocytes from all three
      groups exhibited similar fashion of reduction in PS in response to increased
      stimulus frequency. These data suggest that inherent differences in cardiomyocyte
      excitation-contraction coupling exist between strains, which may warrant caution
      when comparing data from these mouse lines.

PMID- 17014868
TI  - Biochemical mechanism of insulin sensitization, lipid modulation and anti
      atherogenic potential of PPAR alpha/gamma dual agonist: Ragaglitazar.
AB  - The current goal in the treatment of diabetes is not only to enhance the glycemic
      control but also to improve the associated cardiovascular risk factors. Among
      many of the strategies available, a co-ligand of PPARalpha and gamma in a single
      molecule which combines the insulin sensitizing potential of PPARgamma and the
      beneficial lipid modulating properties of PPARalpha agonism, has gained attention
      in the recent past. Here we report the biochemical mechanism by which a dual PPAR
      alpha/gamma agonist Ragaglitazar (Raga) achieves this goal. The PPARalpha
      component of Raga appears to contribute to a significant increase in beta
      oxidation, ApoA1 secretion and inhibition of TG biosynthesis in HepG2 cells.
      These effects of Raga at 60 microM were similar to that shown by Fenofibrate
      (Feno) at 250 microM. The PPARgamma component of Raga showed significant G3PDH
      activity and TG accumulation with a corresponding increase in aP2 expression in
      3T3L1 cells. Significantly reduced levels of IL-6 and TNFalpha were observed in
      the culture supernatants of Raga treated 3T3L1 cells. Raga resulted in
      significant insulin dependent glucose uptake in 3T3L1 with a corresponding
      increase in GLUT4 expression. Further, Raga showed a significant cholesterol
      efflux with a corresponding increase in ABCA1 protein expression in THP-1
      macrophages. In conclusion, Raga activates both PPARalpha and gamma regulated
      pathway in adipocytes as well as in hepatocytes which together contributes for
      its insulin sensitizing and lipid lowering activity. In addition the dual
      activation of PPAR alpha/gamma also shows an athero-protective potential by
      inducing reverse cholesterol efflux and inhibiting the pro-inflammatory
      cytokines.

PMID- 17014869
TI  - Dynamical stabilization of grazing systems: An interplay among plant-water
      interaction, overgrazing and a threshold management policy.
AB  - In a plant-herbivore system, a management strategy called threshold policy is
      proposed to control grazing intensity where the vegetation dynamics is described
      by a plant-water interaction model. It is shown that this policy can lead the
      vegetation density to a previously chosen level under an overgrazing regime. This
      result is obtained despite both the potential occurrence of vegetation collapse
      due to overgrazing and the possibility of complex dynamics sensitive to
      vegetation initial densities and parameter uncertainties.

PMID- 17014870
TI  - Sensitization to the conditioned rewarding effects of morphine modulates gene
      expression in rat hippocampus.
AB  - Opiates addiction is characterized by its long-term persistence. In order to
      study the enduring changes in long-term memory in hippocampus, a pivotal region
      for this process, we used suppression subtractive hybridization to compare
      hippocampal gene expression in morphine and saline-treated rats. Animals were
      subjected to an extended place preference paradigm consisting of four
      conditioning phases. Sensitization to the reinforcing effects of the drug
      occurred after three conditioning phases. After 25 days of treatment rats were
      euthanized and the complementary DNA (cDNA) from the hippocampus of morphine
      dependent and saline-treated animals were then screened for differentially
      expressed cDNAs. The selected 177 clones were then subjected to a microarray
      procedure and 20 clones were found differentially regulated. The pattern of
      regulated genes suggests impairments in neurotransmitter release and the
      activation of neuroprotective pathways.

PMID- 17014872
TI  - Serum leptin and ghrelin levels in response to methylprednisolone injection in
      healthy dogs.
AB  - The aim of this study was to investigate the effects of methylprednisolone
      treatment on serum leptin and ghrelin levels in healthy dogs (n=40). After 14 h
      of fasting, the dogs were injected intramuscularly with saline (control group) or
      methylprednisolone (1, 5 or 10mg/kg). Blood samples were collected prior to
      (baseline) and 2, 3, 4, 8, 12 and 24h subsequent to the treatments. Serum leptin
      and ghrelin were measured by radioimmunoassay. The mean baseline serum leptin and
      ghrelin were 2.5+/-0.1 ng/mL (n=40) and 35.0+/-2.1 pg/mL (n=40), respectively. In
      the control dogs, serum leptin, but not ghrelin levels showed a significant
      fluctuation during the 24h observation period. Serum leptin increased
      significantly (p<0.05-0.01) between 2 and 12h after 1mg/kg of methylprednisolone.
      Serum leptin levels showed biphasic response to 5mg/kg of methylprednisolone: its
      level decreased to 1.9+/-0.1 ng/mL (p<0.01) at 2h and increased at 12h (2.6+/-0.1
      ng/mL) (p<0.01). In response to 10mg/kg of methylprednisolone, serum leptin
      levels decreased significantly (p<0.01) for 24h. Serum ghrelin levels decreased
      to 19+/-5 pg/mL at 2-3h (p<0.01) or increased to 87+/-18 pg/mL at 3-8h (p<0.05
      0.01) after 1mg/kg of methylprednisolone or 10mg/kg of methylprednisolone,
      respectively. Serum ghrelin levels did not change at any time point during 24h
      observation period after 5mg/kg of methylprednisolone. There was a significant
      (p<0.001) inverse correlation (r=-0.635) between serum leptin and ghrelin levels.
      In conclusion, we found that methylprednisolone increases or decreases serum
      leptin and ghrelin levels depending upon its dose and there is a negative
      correlation between serum leptin and ghrelin levels after methylprednisolone
      administration.

PMID- 17014871
TI  - A parametric fMRI investigation of context effects in sensorimotor timing and
      coordination.
AB  - Mounting evidence suggests that information derived from environmental and
      behavioral sources is represented and maintained in the brain in a context
      dependent manner. Here we investigate whether activity patterns underlying
      movements paced according to an internal temporal representation depend on how
      that representation is acquired during a previous pacing phase. We further
      investigate the degree to which context dependence is modulated by different time
      delays between pacing and continuation. BOLD activity was recorded while subjects
      moved at a rate established during a pacing interval involving either
      synchronized or syncopated coordination. Either no-delay or a 3, 6 or 9s delay
      was introduced prior to continuation. Context-dependent regions were identified
      when differences in neural activity generated during pacing continued to be
      observed during continuation despite the intervening delay. This pattern was
      observed in pre-SMA, bilateral lateral premotor cortex, bilateral declive and
      left inferior semi lunar lobule. These regions were more active when continuation
      followed from syncopation than from synchronization regardless of the delay
      length putatively revealing a context-dependent neural representation of the
      temporal interval. Alternatively, task related regions in which coordination
      dependent differences did not persist following the delay, included bilateral
      putamen and supplementary-motor-area. This network may support the differential
      timing demands of coordination. A classic prefrontal-parietal-temporal working
      memory network was active only during continuation possibly providing mnemonic
      support for actively maintaining temporal information during the variable delay.
      This work provides support for the hypothesis that some timing information is
      represented in a task-dependent manner across broad cortical and subcortical
      networks.

PMID- 17014873
TI  - Induction of immune response in mice with a DNA vaccine encoding outer membrane
      protein (omp31) of Brucella melitensis 16M.
AB  - Brucellosis causes serious economic losses to goat farmers by way of reproductive
      losses in the form of abortions and stillbirths. Nucleic acid vaccines provide an
      exciting approach for antigen presentation to the immune system. In this study,
      we evaluated the ability of DNA vaccine encoding the omp31 protein of Brucella
      melitensis 16M to induce cellular and humoral immune responses in mice. We
      constructed eukaryotic expression vectors called pTargeTomp31, encoding outer
      membrane protein (omp31) of B. melitensis 16M. pTargeTomp31 was injected
      intramuscularly three times, at 3-week intervals in groups of mice 6 weeks of
      age. pTargeTomp31 induced good antibody response in ELISA . pTargeTomp31 elicited
      a T-cell-proliferative response and also induced a strong gamma interferon
      production upon restimulation with either the omp31 antigen or B. melitensis 16M
      extract. We also demonstrate that animals immunized with this plasmid elicited a
      strong and long-lived memory immune response. Furthermore, pTargeTomp31 elicited
      a typical T-helper 1-dominated immune response in mice, as determined by
      immunoglobulin G isotype analysis. This vaccine also provided the moderate degree
      of protection to the mice. This study for the first time focuses on DNA
      immunization of a gene from B. melitensis. These results may lead to the
      development of a DNA-based vaccine for the control of brucellosis in goats.

PMID- 17014874
TI  - Plasma hormones in neotropical and domestic cats undergoing routine
      manipulations.
AB  - Many neotropical felines are threatened with extinction and information on their
      physiology is required to assist in conservation. Their reproduction in captivity
      is poor, particularly for the smaller species. Several factors may be
      responsible, but stress is probably the most important. We assayed cortisol, LH,
      FSH, prolactin, testosterone, estradiol, and progesterone in single blood samples
      obtained under sedation from seven neotropical species and, for comparison, in
      stressed and unstressed domestic cats. Cortisol was also assayed in serial blood
      samples obtained after ACTH administration in Leopardus tigrinus, L. wiedi and
      domestic cats. While, in general, the results were fairly consistent, there were
      some statistically significant differences between species that were large enough
      to be of practical importance.

PMID- 17014875
TI  - Elevated cAMP levels reverse Brucella melitensis-induced lipid peroxidation and
      stimulate IL-10 transcription in rats.
AB  - Brucella species are able to survive and replicate within the phagocytic vacuole
      of macrophages that induce chronic infection in humans and domestic animals. The
      activation of oxidative bactericidal activity is one of the defense systems which
      protect the host from the toxic effects of pathogens. The aim of this study was
      to evaluate lipid peroxidation, NO production, antioxidative system and
      inflammation during a period of brucella infection in a rat model; in addition to
      investigate the role of elevated intracellular cyclic AMP on Brucella-induced
      events. Brucella significantly induced lipid peroxidation in plasma, liver and
      spleen by 3-5-fold at 7 days postinfection. NO concentration was significantly
      elevated in the liver and spleen while unchanged in plasma. Cyclic AMP elevating
      agent, rolipram, administration (1mg/kg/day i.p., 3 days) gradually suppressed
      lipid peroxidation and NO formation to the basal level in plasma and spleen
      whilst only a slight decrease was observed in liver. Brucella considerably
      decreased SOD activity in the liver and spleen, with rolipram restoring the
      enzyme activity in liver and activity in spleen being unchanged. Reverse
      transcriptase PCR analyses showed that Brucella melitensis does not alter TNF
      alpha and IFN-gamma transcriptions in liver and spleen. The pathogen did not
      consistently induce nitric oxide synthase mRNA transcriptions in animals; even in
      those housed in the same group. IL-10 transcription was induced by rolipram in
      spleen but not in liver. Our results suggest that activation of the cAMP/PKA
      pathway suppressed lipid peroxidation and the elevated NO concentrations caused
      by B. melitensis. Moreover, rolipram induced anti-inflammatory cytokine IL-10
      transcription and SOD activity, albeit in a tissue dependent manner.

PMID- 17014876
TI  - Successful outcome of hepatic polycystic echinococcosis managed with surgery and
      chemotherapy.
AB  - Echinococcus vogeli has been reported to cause human polycystic echinococcosis. A
      43-year-old Brazilian woman was admitted to hospital complaining of mild
      epigastric discomfort. Computed tomography (CT) revealed multiple cystic lesions
      with calcified edges in several hepatic segments. At exploratory laparotomy,
      polycystic lesions were excised from the liver, omentum and peritoneum. No
      remaining cysts were observed on a post-surgery CT scan. The patient was
      asymptomatic when discharged on Day 19 post-operatively. She was prescribed
      albendazole therapy for 6 months. Follow-up CT performed 11 months later revealed
      no evidence of recurrence. Surgery combined with chemotherapy may improve the
      quality of life of patients with polycystic echinococcosis.

PMID- 17014877
TI  - Cases of typhoid fever imported into England, Scotland and Wales (2000-2003).
AB  - Although typhoid fever is no longer endemic in most of the developed world, it
      remains a major infectious disease in less developed regions and imported cases
      continue to occur in returning travellers, immigrants or migrant workers. We
      analysed all 692 isolates of Salmonella enterica subspecies enterica serovar
      Typhi from cases in England, Scotland and Wales that were sent to the Laboratory
      of Enteric Pathogens at the Health Protection Agency, Centre for Infections,
      London, UK between 2000 and 2003. The country of acquisition was known for 416
      isolates (60%), and the majority of these (70%) came from India or Pakistan.
      Overall, 24 countries were listed, mainly in Asia and Africa. A total of 48 phage
      types were detected, 41% of which were Vi-phage type E1. Antimicrobial
      susceptibility testing revealed that 22% of isolates were multidrug resistant
      (MDR) (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole)
      and 39% were quinolone resistant. A significant number of isolates (n=49) were
      sensitive to nalidixic acid by disk test but exhibited low-level ciprofloxacin
      resistance, suggesting a novel mechanism of resistance and reinforcing the need
      for minimum inhibitory concentration determination. Overall, 13% of isolates were
      both MDR and likely to show a poor response to a fluoroquinolone. A third
      generation cephalosporin (e.g. ceftriaxone) should be considered as empirical
      therapy in regions of the Indian subcontinent where resistance is now at high
      levels as well as in patients returning from these areas. This study helps to
      describe the epidemiology of antimicrobial drug resistance in typhoid fever.

PMID- 17014878
TI  - Morphometric and morphological features of the ventral prostate in rats submitted
      to chronic nicotine and alcohol treatment.
AB  - Clinical studies analyzing simultaneous nicotine-alcohol use by patients showed
      important alterations in various organic systems such as: respiratory, digestory,
      and genital. Also, the prostatic morphology and physiology have been analyzed,
      specially due to large occurrence of prostatic diseases. Then, this work aimed at
      determining the structure and ultrastructure of the prostatic stroma and
      epithelium, as well as the stroma epithelium interactions from rats submitted to
      simultaneous long-term alcohol-nicotine treatment. A total of 40 male rats were
      divided into four groups: control group (10 animals) received tap water;
      alcoholic group (10 animals) received diluted 10% Gay Lussac ethanol; nicotine
      group (10 animals) received a 0.125mg/100g of body weight dose of nicotine
      injected subcutaneosly on a daily basis; nicotine-alcohol group (10 animals)
      received simultaneous alcohol and nicotine treatment. After 90 days of treatment,
      the animals were sacrificed and samples from the ventral lobe of the prostate
      were collected and processed for transmission electron and light microscopies.
      The results showed atrophied epithelium; prostatic intra-epithelial neoplasia;
      dilated cisterns of the granular endoplasmic reticulum, large amounts of collagen
      fibers besides inflammatory cells, specially in the alcoholic and nicotine
      alcohol groups. Therefore, it could be concluded that the association between
      alcohol and nicotine caused the impairment of the prostatic secretory process.
      Moreover, this association is related to prostatic pathogenesis, which could lead
      to late glandular malignancy.

PMID- 17014879
TI  - Antibodies against synthetic epitopes inhibit the enzymatic activity of mutalysin
      II, a metalloproteinase from bushmaster snake venom.
AB  - Mutalysin II (mut-II), a 22.5kDa zinc endopeptidase isolated from bushmaster
      (Lachesis muta muta) snake venom, is a direct acting fibrin(ogen)olytic
      proteinase. It induces monoclonal and polyclonal antibodies which efficiently
      neutralize the hemorrhagic effect of L. muta and several Bothrops whole venoms.
      To characterize epitopes of protective antibodies we have used the Spot method of
      multiple peptide synthesis to prepare 64 overlapping dodecapeptides frameshifted
      by three residues, covering the complete amino acid sequence of mut-II. The
      rabbit anti-mut-II antibodies binding pattern to peptides revealed several
      continuous antigenic regions: one in the N-terminal part, two in the central
      region and the other in the C-terminal of mut-II. By using homology modelling, a
      three-dimensional model of mut-II was built which showed that epitopes are
      surface exposed. Anti-peptide antibodies were raised against three peptides (one
      representative of each epitope region) covalently coupled as a mixture to keyhole
      limpet hemocyanin. Purified IgG from the resulting anti- peptide antibodies cross
      reacted with mut-II and induced a dose-dependent inhibition of the mut-II
      catalyzed proteolysis of fibrinogen.

PMID- 17014880
TI  - Potential of ancestral sylvatic dengue-2 viruses to re-emerge.
AB  - Dengue viruses (DENV) are the most important arboviral pathogens in tropical and
      subtropical regions throughout the world. DENV transmission includes both a
      sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the
      genus Aedes, and an urban, endemic/epidemic cycle between Aedes aegypti, a
      mosquito with larval development in peridomestic water containers, and human
      reservoir hosts. All 4 serotypes of endemic DENV evolved independently from
      ancestral sylvatic viruses and have become both ecologically and evolutionarily
      distinct; this process may have involved adaptation to (i) peridomestic mosquito
      vectors and/or (ii) human reservoir hosts. To test the latter hypothesis, we
      assessed the ability of sylvatic and endemic DENV-2 strains, representing major
      genotypes from Southeast Asia, West Africa and the Americas, to replicate in two
      surrogate human model hosts: monocyte-derived, human dendritic cells (moDCs), and
      mice engrafted with human hepatoma cells. Although the various DENV-2 strains
      showed significant inter-strain variation in mean replication titers in both
      models, no overall difference between sylvatic and endemic strains was detected
      in either model. Our findings suggest that emergence of endemic DENV strains from
      ancestral sylvatic strains may not have required adaptation to replicate more
      efficiently in human reservoir hosts, implying that the potential for re
      emergence of sylvatic dengue strains into the endemic cycle is high. The shared
      replication profiles of the American endemic and sylvatic strains suggest that
      American strains have maintained or regained the ancestral phenotype.

PMID- 17014881
TI  - Assembly of trans-encapsidated recombinant viral vectors engineered from Tobacco
      mosaic virus and Semliki Forest virus and their evaluation as immunogens.
AB  - RNA virus vectors are attractive vaccine delivery agents capable of directing
      high-level gene expression without integration into host cell DNA. However,
      delivery of non-encapsidated RNA viral vectors into animal cells is relatively
      inefficient. By introducing the tobacco mosaic virus (TMV) origin of assembly
      into the RNA genome of Semliki Forest virus (SFV), we generated an SFV expression
      vector that could be efficiently packaged (trans-encapsidated) in vitro by
      purified TMV coat protein (CP). Using cellular assays, pseudovirus disassembly,
      RNA replication and reporter gene expression were demonstrated. We also evaluated
      the immune response to trans-encapsidated recombinant SFV carrying a model
      antigen gene (beta-galactosidase) in C57/B6 mice. Relative to RNA alone, vector
      encapsidation significantly improved the humoral and cellular immune responses.
      Furthermore, reassembly with recombinant TMV CPs permitted the display of peptide
      epitopes on the capsid surface as either genetic fusions or through chemical
      conjugation, to complement the immunoreactivity of the encapsidated RNA genetic
      payload. The SFV vector/TMV CP system described provides an alternative nucleic
      acid delivery mechanism that is safe, easy to manufacture in vitro and that also
      facilitates the generation of unique nucleic acid/protein antigen compositions.

PMID- 17014882
TI  - Metarhodopsin-II stabilization by crosslinked Gtalpha C-terminal peptides and
      implications for the mechanism of GPCR-G protein coupling.
AB  - Metarhodopsin-II is the light-excited form of rhodopsin that triggers G protein
      function. Metarhodopsin-II is stabilized when the N-terminus of the carboxyl (340
      350) tail peptide of the alpha-subunit of transducin (Gtalpha) is crosslinked to
      rhodopsin cysteine 140 or the 340-350 peptide C-terminus of Gtalpha is
      crosslinked to rhodopsin cysteine 316. When the N-terminus of the peptide is
      coupled to C316 the MI<-->MII equilibrium is not affected. The evidence suggests
      that the N-terminus of the 340-350 region of Gtalpha is located near C140 when
      transducin stabilizes metarhodopsin-II and alternative explanations are suggested
      for the effectiveness of the 340-350 Gtalpha tail peptide when bound to C316.

PMID- 17014883
TI  - Cone weights for the two cone-opponent systems in peripheral vision and
      asymmetries of cone contrast sensitivity.
AB  - In understanding the basis of the changes in human color vision across
      eccentricity, one key piece of information remains unknown, whether the relative
      cone weights of the two cone opponent mechanisms vary. Here we measure detection
      threshold contours within three planes in a 3-dimensional cone contrast space to
      reveal the L, M and S-cone weights to the two cone opponent mechanisms, L/M and
      S/(L+M). We find these remain constant across eccentricity suggesting the
      underlying structures of the cone opponent mechanisms are invariant. The contrast
      sensitivities of two poles of the S-cone opponent mechanism also remain
      symmetrical, whereas small asymmetries develop in L/M opponency from about 15
      degrees.

PMID- 17014884
TI  - Separating transducer non-linearities and multiplicative noise in contrast
      discrimination.
AB  - It has been difficult to isolate the factors that limit contrast discrimination,
      one of the most fundamental aspects of the visual system. claim to have found a
      method that can answer the question of why discrimination thresholds increase
      with reference contrast. Is it because of a saturating contrast response function
      or because of increasing (multiplicative) noise? Based on four datasets they
      conclude that multiplicative noise is the controlling factor. disagree and claim
      the jury is still out because only one of the four datasets has sufficiently good
      statistics to support the KCT claim. I reanalyze the KCT data and come to a
      different conclusion. I agree with GM that two of the four datasets have
      thresholds that are too low to be useful in discriminating models and that one
      dataset supports the KCT claim. The fourth dataset is the most interesting one in
      that it provides the strongest support for the KCT claim, but GM throw it out
      because the chi(2) of the best fit is high. The present paper makes a number of
      points: (1) two novel methods are used to fit the fourth dataset. One pair of
      models is based on the strong "finger error" asymmetry between the high and low
      contrast asymptotes of the psychometric function in the fourth dataset. I find
      that some version of multiplicative noise is needed. However, it may be
      multiplicative noise that depends on prior trials rather than just on the present
      trial. (2) Another model that allows the contrast response function to have
      maximal freedom fits the fourth dataset with a reasonable chi square, and with a
      need for multiplicative noise. (3) I examine alternative parameterizations of the
      model functions used by KCT and GM that provide a more intuitive interpretation
      of the parameters. In summary, although I find the data do support a generalized
      form of multiplicative noise, I agree with GM that the jury remains out about
      what are the factors that limit contrast discrimination.

PMID- 17014885
TI  - Characterising mesopic spectral sensitivity from reaction times.
AB  - The spectral sensitivity of the eye was investigated using reaction times to
      broadband chromatic stimuli over a range of background luminances. Relative
      sensitivity was determined from the nonlinear reaction time curve by converting
      reaction times to a linear measure that was independent of spectral sensitivity.
      Two models for mesopic spectral sensitivity were compared. The first was a linear
      combination of V(lambda) and V'(lambda), and the second included input from the L
      M colour-opponent mechanism and the S-cones. The second model produced a
      significantly better fit to the data. The chromatic mechanisms appear to
      contribute to reaction time when there is an appreciable chromatic signal but
      luminance contrast is low.

PMID- 17014886
TI  - Eye dominance effects in feature search.
AB  - We studied the role of eye dominance in non-rivalry conditions, testing dichoptic
      visual search and comparing performance with target presented to the dominant or
      non-dominant eye. Using red-green glasses, subjects viewed an array of green and
      red lines of uniform orientation, with a differently oriented target line present
      on half the trials. Performance was significantly better when the dominant eye
      saw the target, especially when the opposite eye saw the distractors. This effect
      was reduced when only nearest-neighbor surrounding distractors were homogeneous.
      We conclude that the dominant eye has priority in visual processing, perhaps
      including inhibition of non-dominant eye representations.

PMID- 17014887
TI  - 3D shape discrimination using relative disparity derivatives.
AB  - Three-dimensional (3D) shape discrimination could be achieved using relative
      disparity signals or it could be achieved using a higher-order disparity
      derivative detector. Two 3D shape discrimination tasks were used to distinguish
      between these possibilities: a within-shape task and a between-shape task.
      Disparity thresholds were larger when discriminating within the same shape than
      when discriminating between shapes. More importantly, within-shape
      discriminations were dependent on the pedestal disparity (distance from fixation)
      whereas between-shape discriminations were not. The results suggest that a
      mechanism sensitive to higher-order disparity derivatives can achieve
      discrimination between different 3D shapes.

PMID- 17014888
TI  - Retinitis pigmentosa associated with rhodopsin mutations: Correlation between
      phenotypic variability and molecular effects.
AB  - Similar retinitis pigmentosa (RP) phenotypes can result from mutations affecting
      different rhodopsin regions, and distinct amino acid substitutions can cause
      different RP severity and progression rates. Specifically, both the R135L and
      R135W mutations (cytoplasmic end of H3) result in diffuse, severe disease (class
      A), but R135W causes more severe and more rapidly progressive RP than R135L. The
      P180A and G188R mutations (second intradiscal loop) exhibit a mild phenotype with
      regional variability (class B1) and diffuse disease of moderate severity (class
      B2), respectively. Computational and in vitro studies of these mutants provide
      molecular insights into this phenotypic variability.

PMID- 17014889
TI  - Methods for determining microcystins (peptide hepatotoxins) and microcystin
      producing cyanobacteria.
AB  - Episodes of cyanobacterial toxic blooms and fatalities to animals and humans due
      to cyanobacterial toxins (CBT) are known worldwide. The hepatotoxins and
      neurotoxins (cyanotoxins) produced by bloom-forming cyanobacteria have been the
      cause of human and animal health hazards and even death. Prevailing concentration
      of cell bound endotoxin, exotoxin and the toxin variants depend on developmental
      stages of the bloom and the cyanobacterial (CB) species involved. Toxic and non
      toxic strains do not show any predictable morphological difference. The current
      instrumental, immunological and molecular methods applied for determining
      microcystins (peptide hepatotoxins) and microcystin-producing cyanobacteria are
      reviewed.

PMID- 17014890
TI  - A critical review of the German Paleolithic hominin record.
AB  - We review the hominin fossil record from western Central Europe in light of the
      recent major revisions of the geochronological context. The mandible from Mauer
      (Homo heidelbergensis), dated to circa 500,000 years ago, continues to represent
      the earliest German hominin and may coincide with the occupation of Europe north
      of the high alpine mountain chains. Only limited new evidence is available for
      the Middle Pleistocene, mostly in the form of skull fragments, a pattern that may
      relate to taphonomic processes. These finds and their ages suggest the gradual
      evolution of a suite of Neandertal features during this period. Despite new finds
      of classic Neandertals, there is no clear proof for Neandertal burial from
      Germany. Alternatively, cut marks on a skull fragment from the Neandertal type
      site suggest special treatment of that individual. New Accelerator Mass
      Spectrometry (AMS) radiocarbon dates of previous finds leave little reliably
      dated evidence for anatomically modern humans (AMH) in Europe before 30,000 BP;
      the remains from Hahnofersand, Binshof-Speyer, Paderborn-Sande, and Vogelherd are
      now of Holocene age. Thus, a correlation of AMH with the Aurignacian remains to
      be proven, and the general idea of a long coexistence of Neandertals and AMH in
      Europe may be questioned. In western Central Europe, evidence of Gravettian human
      fossils is also very limited, although a new double grave from lower Austria may
      be relevant. The only dated burial from the German Upper Paleolithic (from
      Mittlere Klause) falls into a time period (circa 18,600 BP) represented by only a
      few occupation sites in western Central Europe. A number of human remains at
      Magdalenian sites appear to result from variable (secondary) burial practices. In
      contrast, the Final Paleolithic (circa 12,000-9600 cal. BC) yields an increase of
      hominin finds, including multiple burials (Bonn-Oberkassel, Neuwied-Irlich),
      similar to the situation in western and southern Europe.

PMID- 17014891
TI  - Influences of carbonate and chloride ions on persulfate oxidation of
      trichloroethylene at 20 degrees C.
AB  - Application of in situ chemical oxidation (ISCO) involves application of oxidants
      to contaminants such as trichloroethylene (TCE) in soil or groundwater in place.
      Successful application of ISCO at a hazardous waste site requires understanding
      the scavenging reactions that could take place at the site to better optimize the
      oxidation of target contaminants and identification of site conditions where ISCO
      using persulfate may not be applicable. Additionally, estimation of the oxidant
      dose at a site would need identification of groundwater constituents such as
      alkalinity and chlorides that may scavenge radicals and therefore use up the
      oxidant that is targeted for the contaminant(s). The objective of this study was
      to investigate the influence of various levels of chloride and carbonates on
      persulfate oxidation of TCE at 20 degrees C under controlled conditions in a
      laboratory. Based on the results of the laboratory experiments, both chloride and
      alkalinity were shown to have scavenging effects on the rate of oxidation of TCE.
      It was found that at a neutral pH, persulfate oxidation of TCE was not affected
      by the presence of bicarbonate/carbonate concentrations within the range of 0
      9.20 mM. However, the TCE degradation rate was seen to reduce with an increase in
      the level of carbonate species and at elevated pHs. TCE degradation in the
      presence of chlorides revealed no effect on the degradation rate especially at
      chloride levels below 0.2 M. However, at chloride levels greater than 0.2 M, TCE
      degradation rate was seen to reduce with an increase in the chloride ion
      concentration. Prior to application of persulfate as an oxidant, a site should be
      screened for the presence of scavengers to evaluate the potential of meeting
      target cleanup goals within a desirable timeframe at the site.

PMID- 17014892
TI  - Identification of factor IX mutations in Iranian haemophilia B patients by SSCP
      and sequencing.
AB  - Different kinds of mutations, mostly point mutations, in the coagulation factor
      IX (FIX) gene F9 result in a recessive X-linked bleeding disorder known as
      haemophilia B. In this study, molecular analysis of 76 unrelated Iranian
      haemophilia B patients was performed by PCR, single strand conformational
      polymorphism (SSCP) on important functional regions of the F9 gene followed by
      sequencing on samples with different migration pattern. Using this approach we
      found mutation in 52 out of 76 patients. Our data showed that the pathologic
      mechanisms are heterogeneous as recorded for patients in haemophilia B mutation
      database and seven of the mutations are previously undescribed.

PMID- 17014893
TI  - The dietary soy flavonoid genistein abrogates tissue factor induction in
      endothelial cells induced by the atherogenic oxidized phospholipid oxPAPC.
AB  - INTRODUCTION: Tissue factor (TF) plays a pivotal role in the generation of
      thrombin in atherothrombotic disease. The oxidized phospholipid 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC), an active compound of
      minimally oxidized low-density lipoprotein (MM-LDL), induces TF in endothelial
      cells (EC). The dietary soybean isoflavonoid genistein has been claimed to
      reverse several processes leading to atherosclerosis and related cardiovascular
      events via binding to estrogen receptors, generating nitric oxide (NO) or
      inhibiting tyrosine kinase-dependent pathways. METHODS AND MATERIALS: The effects
      and mechanisms of genistein on activity, antigen expression and mRNA levels of
      oxPAPC-induced TF were studied in human umbilical vein endothelial cells (HUVEC)
      and human aortic endothelial cells (HAEC). RESULTS AND CONCLUSIONS: Genistein
      abrogated oxPAPC-induced TF activity in arterial and venous human EC to basal
      levels, as measured by functional clotting assay, and downregulated oxPAPC
      induced antigen expression measured by flow cytometry and mRNA levels quantified
      by real-time PCR. Western blotting and inhibitor experiments with the estrogen
      receptor inhibitor ICI 182,780 and the NO-synthase inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) showed that the effect may be mediated via
      inhibition of phosphorylation of ERK, but not upstream MEK1/2. The effect is not
      mediated by the tyrosine kinase inhibitor activity of genistein, as another
      tyrosine kinase inhibitor (tyrphostin 25) had no effect. Binding to the estrogen
      receptor or generation of NO are not involved in the action of genistein on TF.
      In conclusion genistein reduces oxPAPC-induced TF expression and thereby the
      prothrombotic phenotype of EC, further substantiating and explaining the
      beneficial effects of dietary genistein in preventing atherosclerosis and related
      cardiovascular events.

PMID- 17014894
TI  - Transitional angiogenesis and vascular remodeling during coronary angiogenesis in
      response to myocardial infarction.
AB  - Coronary artery disease (CAD) is a major source of morbidity and mortality in the
      industrialized world. CAD causes ischemia as a prelude to angina, myocardial
      infarction and heart failure as specific forms of heart disease causing a decline
      in the quality of life. CAD or atherosclerosis and the resulting myocardial
      ischemia trigger a natural angiogenic response that generates collateral
      circulations. The long-term goal for these studies is to develop therapeutic
      angiogenesis that augments the natural coronary angiogenesis. This project makes
      use of an infarcted transgenic mouse model to characterize formation of those
      collateral circulations in the post-infraction heart. The experiments utilized
      thoracotomy and a microcauterizer to produce an infarct in transgenic mice and
      this stimulated neovascularization and allowed labeling of the coronary vessels,
      thereby defining the morphogenic processes involved in formation of collateral
      circulations. The results show that the heart consistently responds to infarcts
      with angiogenesis at 1d post-treatment (PT) that undergoes transition into
      vascular remodeling at 7d PT with complete remodeling at 14d PT. The vascular
      remodeling appears to mitigate any net increase in perfusion that may be achieved
      early in coronary angiogenesis. The results suggest that therapeutic approaches
      need to shift from an exclusive focus on stimulating angiogenesis to include
      modulation of vascular remodeling for increased long-term myocardial perfusion.

PMID- 17014895
TI  - Vibroacoustic disease: biological effects of infrasound and low-frequency noise
      explained by mechanotransduction cellular signalling.
AB  - At present, infrasound (0-20 Hz) and low-frequency noise (20-500 Hz) (ILFN, 0-500
      Hz) are agents of disease that go unchecked. Vibroacoustic disease (VAD) is a
      whole-body pathology that develops in individuals excessively exposed to ILFN.
      VAD has been diagnosed within several professional groups employed within the
      aeronautical industry, and in other heavy industries. However, given the
      ubiquitous nature of ILFN and the absence of legislation concerning ILFN, VAD is
      increasingly being diagnosed among members of the general population, including
      children. VAD is associated with the abnormal growth of extra-cellular matrices
      (collagen and elastin), in the absence of an inflammatory process. In VAD, the
      end-product of collagen and elastin growth is reinforcement of structural
      integrity. This is seen in blood vessels, cardiac structures, trachea, lung, and
      kidney of both VAD patients and ILFN-exposed animals. VAD is, essentially, a
      mechanotransduction disease. Inter- and intra-cellular communication is achieved
      through both biochemical and mechanotranduction signalling. When the structural
      components of tissue are altered, as is seen in ILFN-exposed specimens, the
      mechanically mediated signalling is, at best, impaired. Common medical diagnostic
      tests, such as EKG, EEG, as well as many blood chemistry analyses, are based on
      the mal-function of biochemical signalling processes. VAD patients typically
      present normal values for these tests. However, when echocardiography, brain MRI
      or histological studies are performed, where structural changes can be
      identified, all consistently show significant changes in VAD patients and ILFN
      exposed animals. Frequency-specific effects are not yet known, valid dose
      responses have been difficult to identify, and large-scale epidemiological
      studies are still lacking.

PMID- 17014896
TI  - Voltage-gated K+ channels are associated with cell proliferation and cell cycle
      of ovarian cancer cell.
AB  - OBJECTIVES: To study the role of Voltage-gated potassium ion channels (Kv) in
      cell proliferation and cell cycle of ovarian cancer cell. METHODS: The effects of
      voltage-gate K+ channels on human ovarian cancer cell line (A2780 cell)
      proliferation and cell cycle were observed by means of MTT and flow cytometry. A
      variety of K+ channel blockers were used in order to differentiate the critical
      subtype of K+ channels involved. Mechanism of K+ channel in cell proliferation
      was explored by studying the relationship between the K+ channel and Ca2+ entry.
      Kv and L-type Ca2+ channel gene expressions were determined by RT-PCR. RESULTS: 4
      Aminopyridine, an inhibitor of voltage-gated K+ channels, significantly inhibited
      the proliferation of A2780 cells as measured by MTT. 4-Aminopyridine also
      significantly affected the cell cycle, which increased the percentage of cells in
      G0/G1, and reduced the percentage of cells in S phase and G2/M phase. Non
      selective K+ channel blockers tetrapentylammonium (TPeA) and verapamil had
      similar inhibitory effects on A2780 cell proliferation and cell cycle. In
      contrast, iberiotoxin, a selective inhibitor of KCa channels, and glibenclamide,
      a potent inhibitor of KATP channels, had no effect on the cell proliferation and
      cell cycle of A2780. Moreover K+ channels inhibitor, TPeA and verapamil, can
      blocked Ca2+ influx in these cells. CONCLUSION: Voltage-gated K+ channels play an
      important role in the proliferation and cell cycle of ovarian cancer cell. It is
      likely that the influence of Kv channels on A2780 cell proliferation and cell
      cycle is mediated by a Ca2+-dependent mechanism.

PMID- 17014897
TI  - Thromboembolic complications in patients with clear cell carcinoma of the ovary.
AB  - OBJECTIVE: The purpose of this study was to define the incidence of deep venous
      thrombosis (DVT) and pulmonary embolism (PE) in patients with clear cell
      carcinoma (CCC) of the ovary and to investigate the prognostic factors in such
      patients. METHODS: Between January 1987 and December 2003, 641 women with primary
      invasive epithelial ovarian cancer underwent treatment at the Royal Hospital for
      Women in Sydney, Australia. Sixty-six patients (10.3%) with CCC were identified
      from the data bank, and their data were compared with a matched-control group of
      132 patients with non-clear cell epithelial ovarian carcinoma. RESULTS: A
      thromboembolic event (DVT or PE) was noted in 27.3% of patients with CCC,
      compared to 6.8% of patients with other epithelial ovarian cancers. PE was
      detected in 13.6% and 3.8% of patients, respectively. In patients with CCC, DVT
      was frequently observed before operation or at the time of recurrence. In a
      multivariate analysis of patients matched for age and stage, the occurrence of a
      DVT or the presence of endometriosis was significant predictors of clear cell
      histology. Within the clear cell group, no particular risk factor for DVT could
      be identified. Metastases of 50 mm or greater in diameter, ascites of 1000 ml or
      more, advanced FIGO stage, and the occurrence of DVT were poor prognostic factors
      for CCC in univariate analysis, but in a multivariate Cox regression analysis,
      only FIGO stage and occurrence of DVT remained significant. CONCLUSION: The
      incidence of venous thromboembolic events was found to be significantly higher in
      patients with CCC when compared to patients with other epithelial ovarian
      cancers.

PMID- 17014898
TI  - The prognostic significance of positive peritoneal cytology and adnexal/serosal
      metastasis in stage IIIA endometrial cancer.
AB  - OBJECTIVE: The clinical significance and optimal management of patients with
      stage IIIA endometrial cancer are controversial. We sought to determine whether
      recurrence and survival of patients with stage IIIA endometrial cancer differ
      with surgical pathologic findings (positive peritoneal cytology versus positive
      adnexae or serosa) and adjuvant treatment. METHODS: Retrospective single
      institution analysis of patients surgically staged for IIIA endometrial cancer at
      Duke University Medical Center from 1973 to 2002. Stage IIIA patients were
      stratified into positive cytology alone (group IIIA1, n=37) and positive adnexae
      or uterine serosa (group IIIA2, n=20). Comparison was made with previously
      reported group of 467 patients with surgical stage I/II disease. Recurrence and
      survival were analyzed using Kaplan-Meier estimations and Cox proportional
      hazards model. RESULTS: Mean age of 57 patients with stage IIIA endometrial
      cancer was 63. Adjuvant therapies were administered to 89% patients (74%
      radiotherapy, 4% chemotherapy, 19% progestins). Five-year overall (OS) and
      recurrence-free disease-specific survival (RFDSS) were 64% and 76%, respectively.
      Survival was similar comparing IIIA1 (62%) and IIIA2 (68%, p=0.999). RFDSS by
      adjuvant therapy was: external beam radiotherapy 89% (n=10), intraperitoneal P32
      84% (n=21), progestins 78% (n=9), none 75% (n=6). 61% recurrences included
      extrapelvic component. In multivariable analysis of stage I-IIIA patients
      (n=517), positive cytology but not adnexal/serosal metastasis was predictive of
      death (HR 1.70, 95% CI 1.06-2.73) and disease recurrence (HR 1.70, 95% CI 1.07
      2.71). CONCLUSION: Among patients with stage IIIA endometrial cancer, metastasis
      to adnexae or serosa does not appear to confer worse prognosis than positive
      cytology alone. Positive cytology is an independent predictor of prognosis among
      patients with stage I-IIIA endometrial cancer. While optimal adjuvant therapy for
      these groups remains unclear, recurrence patterns suggest that systemic therapies
      are appropriate.

PMID- 17014899
TI  - Tertiary cytoreductive surgery in recurrent ovarian cancer: selection criteria
      and survival outcome.
AB  - OBJECTIVES: Studies of tertiary cytoreductive surgery (TCS) in recurrent
      epithelial ovarian cancer are limited, and appropriate patient selection remains
      a clinical challenge. We sought to evaluate the impact of TCS on survival and to
      determine predictors of optimal tertiary resection. METHODS: Between January 1997
      and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at
      two institutions. All patients received initial platinum and taxane-based
      chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors
      and survival were retrospectively abstracted from medical records. Optimal TCS
      was defined as microscopic residual disease. RESULTS: Thirty of 47 (64%) patients
      underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was
      the only significant predictor of achieving optimal TCS. Overall survival after
      TCS was statistically longer in patients with microscopic versus macroscopic
      residual disease (24 versus 16 months, p=0.03). After controlling for age, time
      to progression and optimal TCS, only the presence of diffuse disease at tertiary
      exploration remained a significant poor predictor of survival. However, in a
      cohort of patients with limited disease implants, multivariate analysis indicated
      that optimal TCS retained prognostic significance as a positive predictor of
      survival. Twelve patients (26%) experienced severe postoperative complications,
      including six with pulmonary embolism, four with fistulae and two with
      postoperative myocardial infarctions. CONCLUSIONS: Size of disease implants on
      preoperative imaging may guide the selection of candidates for TCS. In those
      patients with limited disease implants at laparotomy, optimal TCS is associated
      with improved survival.

PMID- 17014900
TI  - The many faces of progesterone: a role in adult and developing male brain.
AB  - In addition to its well documented action in female-typical behaviors,
      progesterone exerts an influence on the brain and behavior of males. This review
      will discuss the role of progesterone and its receptor in male-typical
      reproductive behaviors in adulthood and the role of progesterone and its receptor
      in neural development, in both sexual differentiation of the brain as well as in
      the development of "non-reproductive" functions. The seemingly inconsistent and
      contradictory results on progesterone in males that exist in the literature
      illustrate the complexity of progesterone's actions and illuminate the need for
      further research in this area. As progestin-containing contraceptives in men are
      currently being tested and progesterone administration to pregnant women and
      premature newborns increases, a better understanding of the role of this hormone
      in behavior and brain development becomes essential.

PMID- 17014901
TI  - Effect of oocyte diameter on meiotic competence, embryo development, p34 (cdc2)
      expression and MPF activity in prepubertal goat oocytes.
AB  - The aim of this study was to analyze the relationship between oocyte diameter,
      meiotic and embryo developmental competence and the expression of the catalytic
      subunit of MPF, the p34(cdc2), at mRNA, RNA and protein level, as well as its
      kinase activity, in prepubertal (1-2 months old) goat oocytes. MPF is the main
      meiotic regulator and a possible regulator of cytoplasmic maturation; therefore,
      it could be a key factor in understanding the differences between competent and
      incompetent oocytes. Oocytes were classified according to oocyte diameter in four
      categories: <110, 110-125, 125-135 and >135 microm and matured, fertilized and
      cultured in vitro. The p34(cdc2) was analyzed in oocytes at the time of
      collection (0 h) and after 27 h of IVM (27 h) in each of the oocyte diameter
      categories. The oocyte diameter was positively related to the percentage of
      oocytes at MII after IVM (0, 20.7, 58 and 78%, respectively) and the percentage
      of blastocysts obtained at 8 days postinsemination (0, 0, 1.95 and 12.5%,
      respectively). The expression of RNA and mRNA p34(cdc2) did not vary between
      oocyte diameters at 0 and 27h. Protein expression of p34(cdc2) increased in each
      oocyte category after 27 h of maturation. MPF activity among diameter groups did
      not vary at 0h but after IVM there was a clear and statistically significant
      increase of MPF activity in the biggest oocytes.

PMID- 17014902
TI  - Children of mothers at psychosocial risk growing up: a follow up at the age of
      16.
AB  - The aim of the present study was to make a 16-year follow-up of children of
      psychosocial risk mothers as concerns emotional/behavioural problems, self
      esteem, life events, and academic grades. Forty-three teenagers (index group) and
      61 reference teenagers were personally interviewed and asked to answer the Youth
      Self-report (YSR), the Self-image questionnaire I Think I Am, and a Life Event
      questionnaire. Their final grades from the 9-year compulsory school were studied.
      The results showed that boys, especially the sons from families with alcohol/drug
      problems, displayed poorer mental health, a more negative self-image, had
      experienced more negative life events, and had to a greater extent not
      successfully completed the 9-year compulsory school. More teenagers in the index
      group had been placed in foster care, had a less positive outlook about their
      future, were more often smokers, and more of them (girls) had seriously
      considered committing suicide than the teenagers in the reference group. It was
      concluded that boys of psychosocial risk mothers are less well off than teenagers
      of non-risk mothers at the age of 16 as concerns psychosocial well being. It is
      of great importance to devote attention to these children at an early stage of
      life in order to be able to provide them with the support that may prevent
      development of future problems.

PMID- 17014903
TI  - Precipitation of heavy metals in produced water: influence on contaminant
      transport and toxicity.
AB  - Produced water undergoes changes in its physical chemistry including
      precipitation of heavy metals after being discharged and mixed with ambient
      seawater. Potential impacts of the precipitation of heavy metals on their
      transport and toxicity were studied using samples from offshore oil production
      sites on the Scotian Shelf off eastern Canada. Concentrations of aluminum,
      cadmium, chromium, cobalt, copper, iron, lead, manganese, nickel and zinc were
      measured in total, particulate and dissolved fractions together with Microtox
      tests for assessment of toxicity. Heavy metals in produced water were transformed
      from dissolved to particulate phase in a period of hours under oxygenated
      conditions, and aggregated to larger particles that settle rapidly (>100 m/day)
      over a few days. In addition, there was production of buoyant particles comprised
      of heavy metal precipitates sequestered onto oil droplets that were transported
      to the surface. The particulate fraction was generally more toxic than the
      dissolved fraction. This was evident at the mixing interface between produced
      water and seawater where elevated particulate and toxicity levels were observed.
      Laboratory studies suggest an increase in the toxicity of discharged produced
      water over time. Time-series experiments showed a sustained toxic response for
      more than a week following the oxidation of freshly discharged produced water
      that initially elicited little or no toxic response in the Microtox test.
      Chemical processes identified in this study, namely precipitation of heavy metals
      and consequent settling and rising fluxes of particles, will influence the
      toxicity, the fate and the transport of potential contaminants in the produced
      water. Therefore, these processes need to be considered in assessment of the
      environmental impact associated with offshore oil and gas operations.

PMID- 17014905
TI  - The alteration of cell membrane charge after cultured on polymer membranes.
AB  - In this work, cell electrophoresis, measuring the electrophoretic mobility of
      cells, was used to investigate the variation of surface charge property of cells
      after cultured on different polymer membranes. HepG2 cell line, derived from a
      well-differentiated, human hepatoma, was used as a model cell. The polymer
      biomaterials used in this study included polyvinyl alcohol (PVA), poly(ethylene
      co-vinyl alcohol) (EVAL), and polyvinylidene fluoride (PVDF). For cells cultured
      in the presence of serum, cell mobility after being cultured on PVA substrates
      was considerably higher than that on EVAL or PVDF substrates. This effect was
      completely suppressed by cycloheximide (CHX) in the serum-free medium. Taken
      together, the cell surface charge property can be altered after cells cultured on
      different polymer substrates. The precise mechanism by which the variation of
      electrophoretic mobility of cultured cells is unknown, but it is reasonable to
      assume that the polymer substrates could influence the absorption of serum
      proteins on cell membrane surface to change cell electrophoretic mobility and,
      simultaneously, to regulate adhesion, growth and function of cultured cells.

PMID- 17014906
TI  - Impact of family abuse on running away, deviance, and street victimization among
      homeless rural and urban youth.
AB  - PROBLEM: Various demographic and familial risk factors have been linked to
      runaway behavior. To date, there has not been a systematic investigation of the
      impact of size of community on runaway behavior. This study will compare runaways
      from smaller cities and rural areas to their urban counterparts. METHODS: A
      convenience sample of 602 adolescents was interviewed between 1995 and August of
      1996 in Missouri, Iowa, Nebraska, and Kansas, USA. Multiple regression was used
      to examine the association between gender, neglect, sexual abuse, physical abuse,
      geographic and family structure change, and community size of first runaway to
      predict age at first runaway, deviant subsistence strategies, and street
      victimization. RESULTS: Findings indicate that adolescents exposed to neglect
      (beta=-.20) and sexual abuse (beta=-.16) ran away sooner and were more likely to
      be victimized on the street. Rural adolescents who experienced higher levels of
      physical abuse relied more heavily on deviant subsistence strategies (beta=.15)
      and remained in abusive homes longer (beta=.15) than their similarly situated
      urban counterparts. CONCLUSIONS: Rural youth who have been subjected to elevated
      levels of familial abuse are at greater risk of deviant subsistence strategies,
      which increase the likelihood of street victimization.

PMID- 17014907
TI  - Who is caring for our most vulnerable children? The motivation to foster in child
      welfare.
AB  - OBJECTIVE: Responding to the need for more foster families to provide care for
      increasing numbers of children coming into care, this study was designed to
      understand the motivations and needs of foster parents in order to improve
      recruitment and retention. To meet this goal, the study identified
      characteristics of current foster families, performed a factor analysis on the
      Foster Parent Satisfaction Survey (FPSS) (Denby, R. W., Rindfleisch, N., & Bean,
      G. 1999). Predictors of foster parent's satisfaction and intent to continue to
      foster were identified, and the results were used to differentiate between foster
      parents who did and did not consider quitting fostering. METHOD: A sample of 652
      foster parents completed a survey of 139 items including the Foster Parent
      Satisfaction Survey [Denby, R. W., Rindfleisch, N., & Bean, G. (1999). Predictors
      of foster parent's satisfaction and intent to continue to foster. Child Abuse &
      Neglect, 23, 287-303]. RESULTS: Foster parents were motivated by wanting to be
      loving parents to children and saving children from harm. The factor analysis of
      the FPSS resulted in five factors that were consistent with typical scoring
      methods of the instrument. A discriminant function analysis using these factors
      and whether parents had considered quitting fostering revealed that one factor,
      Challenging Aspects of Fostering, correctly classified 75.5% of parents.
      CONCLUSIONS: Foster parents' satisfaction is related to their perceptions about
      teamwork, communication, and confidence in relation to both the child welfare
      agency and its professionals. Further, the most frequently endorsed reasons for
      fostering reflected foster parents' altruistic and internal motivations to
      foster. Negative relationships with professional staff from the child welfare
      agency were linked to considering quitting fostering.

PMID- 17014908
TI  - Compassion fatigue, burnout, and compassion satisfaction among Colorado child
      protection workers.
AB  - OBJECTIVE: The goal of this study was to understand better the risk of compassion
      fatigue (the trauma suffered by the helping professional) and burnout (emotional
      exhaustion, depersonalization, and reduced sense of personal accomplishment), and
      the potential for compassion satisfaction (the fulfillment from helping others
      and positive collegial relationships) among Colorado county child protection
      staff using the Compassion Satisfaction/Fatigue Self-Test [Figley, C. R., &
      Stamm, B. H. (1996). Psychometric review of Compassion Fatigue Self-Test. In B.
      H. Stamm (Ed.), Measurement of stress, trauma, and adaptation (pp. 127-130).
      Lutherville, MD: Sidran Press]. An additional goal was to test the relationship
      of these three constructs to each other. METHOD: A self-report instrument
      developed by Stamm and Figley was used to measure the risk of compassion fatigue
      and burnout and the potential for compassion satisfaction among 363 child
      protection staff participating in a secondary trauma training seminar. RESULTS:
      Participants were significantly more likely to have high risk of compassion
      fatigue, extremely low risk of burnout, and good potential for compassion
      satisfaction. Participants with high compassion satisfaction had lower levels of
      compassion fatigue (p=.000; mean=35.73 high compassion satisfaction group,
      mean=43.56 low group) and lower levels of burnout (p=.000; mean=32.99 high
      compassion satisfaction group, mean=41.69 low group). CONCLUSION: Approximately
      50% of Colorado county child protection staff suffered from "high" or "very high"
      levels of compassion fatigue. The risk of burnout was considerably lower. More
      than 70% of staff expressed a "high" or "good" potential for compassion
      satisfaction. We believe compassion satisfaction may help mitigate the effects of
      burnout.

PMID- 17014909
TI  - Risk characterization and exposure assessment in arseniasis-endemic areas of
      Taiwan.
AB  - This paper examines the age-specific human health risks exposed to inorganic
      arsenic through arsenic-contaminated farmed fish/shrimp and groundwater
      consumptions in arseniasis-endemic areas of blackfoot disease (BFD)-endemic area
      and Lanyang Plain in Taiwan, based on an probabilistic integrated risk assessment
      framework. We employ an age-dependent predictive physiologically-based
      pharmacokinetic model to account for arsenic concentrations in target organs. We
      reconstruct age-specific dose-response profiles for arsenicosis and arsenic
      induced cancers by best fitting a pharmacodynamics-based three-parameter Hill
      equation model to published epidemiological data from West Bengal and Taiwan. The
      predicted median arsenic concentrations in age group-specific skin, lung, and
      bladder ranged from 2.24-5.70, 3.76-9.46, and 5.11-20.71 micro g g(-1) in BFD
      endemic area, whereas 4.98-12.04, 8.23-19.92, and 11.07-43.45 micro g g(-1) in
      Lanyang Plain, respectively. Risk analysis indicates that consumption of arsenic
      contaminated farmed fish/shrimp and groundwater in arseniasis-endemic areas may
      increase threat to prevalence of arsenicosis for all age groups, whereas adults
      may undergo potential risks of arsenic-induced skin, lung and bladder cancers. We
      show that peoples in Lanyang Plain are more readily associated with higher
      morbidities for arsenicosis and skin cancer as well as fatalities for lung and
      bladder cancers than that of peoples in BFD-endemic area. Here we report the
      first case in which theoretical human health risks for consuming As-contaminated
      farmed fish/shrimp and groundwater in the arseniasis-endemic areas are alarming
      under a conservative condition based on a probabilistic risk assessment
      framework.

PMID- 17014910
TI  - Early brain development disruption from NMDA receptor hypofunction: relevance to
      schizophrenia.
AB  - Disruption to brain development at an early stage can potentially alter
      chemically coded neural networks and can affect behavior in later life. During
      early brain development antagonism of glutamate NMDA receptors, which play an
      important role in neuronal outgrowth and survival, leads to neuronal damage in
      several brain regions and causes behavioral alterations in rodents that mimic
      schizophrenia symptoms and endophenotypes. There are several lines of evidence
      implicating involvement of a dysfunctional glutamate system in schizophrenia. In
      normal subjects, NMDA receptor antagonists produce behavioral and neurochemical
      changes that mimic schizophrenia symptoms better than any other psychotomimetic
      drug. Moreover, these drugs worsen symptoms in schizophrenia patients and can
      trigger a recrudescence of the acute psychotic state in patients with stable
      chronic schizophrenia. In addition, genes consistently reported as being altered
      in schizophrenia play roles in development, neuroplasticity and
      glutamate/GABAergic neurotransmission. Perinatal NMDA receptor antagonist
      treatment is a useful model for studying the neurodevelopmental and NMDA receptor
      hypofunction hypotheses of schizophrenia because neurochemical and behavioral
      changes, reminiscent of those seen in schizophrenia, are present long after
      cessation of drug administration, which suggests that a permanent change in brain
      structure and organization has occurred during brain development.

PMID- 17014911
TI  - Consistent affection of the central somatosensory system in spinocerebellar
      ataxia type 2 and type 3 and its significance for clinical symptoms and
      rehabilitative therapy.
AB  - The spinocerebellar ataxias type 2 (SCA2) and type 3 (SCA3) are progressive,
      currently untreatable and ultimately fatal ataxic disorders, which belong to the
      group of neurological disorders known as CAG-repeat or polyglutamine diseases.
      Since knowledge regarding the involvement of the central somatosensory system in
      SCA2 and SCA3 currently is only fragmentary, a variety of somatosensory disease
      signs remained unexplained or widely misunderstood. The present review (1) draws
      on the current knowledge in the field of neuroanatomy, (2) describes the anatomy
      and functional neuroanatomy of the human central somatosensory system, (3)
      provides an overview of recent findings regarding the affection of the central
      somatosensory system in SCA2 and SCA3 patients, and (4) points out the
      underestimated pathogenic role of the central somatosensory system for
      somatosensory and somatomotor disease symptoms in SCA2 and SCA3. Finally, based
      on recent findings in the research fields of neuropathology and neural
      plasticity, this review supports currently applied and recommends further
      neurorehabilitative approaches aimed at maintaining, improving, and/or recovering
      adequate somatomotor output by enforcing and changing somatosensory input in the
      very early clinical stages of SCA2 and SCA3.

PMID- 17014912
TI  - A pragmatic, unblinded randomised controlled trial comparing an occupational
      therapy-led lifestyle approach and routine GP care for panic disorder treatment
      in primary care.
AB  - BACKGROUND: Treated anxiety increased in the UK by over 30% since 1994.
      Medication and psychological treatment is most common, but outcomes are sometimes
      poor, with high relapse rates. Lifestyle has a potential role in treatment, but
      is not considered in clinical guidelines. Panic disorder is potentially
      influenced by lifestyle factors. METHODS: 16 week unblinded pragmatic randomised
      controlled trial in 15 East of England primary care practices (2 Primary Care
      Trusts). Participants met DSM-IV criteria for panic disorder with/without
      agoraphobia. Follow-up at 20 weeks and 10 months. Control arm, unrestricted
      routine GP care. Trial Arm, Occupational therapy-led lifestyle treatment
      comprising: lifestyle review of fluid intake, diet pattern, exercise, caffeine,
      alcohol and nicotine; negotiation of positive lifestyle changes; monitoring and
      review of impact of changes. PRIMARY OUTCOME MEASURE: Beck Anxiety Inventory.
      DATA ANALYSIS: Intention-to-treat analysis provided between-group comparisons
      using analysis of co-variance. Bonferroni method to adjust p-values. RESULTS:
      From 199 referrals, 36 GP care and 31 lifestyle arm patients completed to final
      follow-up. Significantly lower lifestyle arm BAI scores at 20 weeks (p<0.001),
      non-significant (p=0.167) at 10 months after Bonferroni correction. 63.6%
      lifestyle arm, and 40% GP arm patients (p=0.045) panic-free at 20 weeks; 67.7%
      and 48.5% (p=0.123) respectively at 10 months. LIMITATIONS: Final study
      size/power calls for caution in interpreting findings. CONCLUSIONS: A lifestyle
      approach may provide a clinically effective intervention at least as effective as
      routine GP care, with significant improvements in anxiety compared with routine
      GP care at the end of treatment. Further study is required before suggesting
      practice changes.

PMID- 17014913
TI  - Macrophages in human fallopian tube and ovarian epithelial inclusion cysts.
AB  - Epithelial inclusion cysts (EICs) are considered a preferential site for ovarian
      carcinogenesis. Local inflammation, associated to ovulatory wound repair and
      epithelial inflammatory conditions, facilitates EIC formation and involves
      activation of macrophages. The aim of this study was to analyse the presence and
      numbers of macrophages in the ovarian surface epithelium (OSE), in EICs, and in
      the fallopian tubes, as tubal metaplasia is a common finding in EICs.
      Immunohistochemical analysis of macrophages was performed in 25 fallopian tubes
      in different phases of the menstrual cycle, and in 30 ovaries showing EICs from
      cycling and postmenopausal women. In the fallopian tube, macrophages were
      abundant and underwent cyclic changes during the menstrual cycle, being
      particularly abundant within the epithelium at early and mid-luteal phases.
      Macrophages were not found in the normal OSE. However, OSE areas and EICs showing
      tubal metaplasia were invariably associated with infiltration by abundant
      macrophages. Macrophages were present among epithelial cells, infiltrating the
      cyst wall, as well as free in the cyst lumen. No significant differences existed
      between follicular and luteal phases of the cycle, or between cycling and
      postmenopausal women. This study has demonstrated that macrophages are associated
      with metaplastic EICs, and raises the possibility that these cells contribute to
      the particular microenvironment of EICs through secretion of cytokines and growth
      factors that may reach bioactive concentrations in the confined space of the
      EICs.

PMID- 17014915
TI  - Immunogenicity of a chimeric hepatitis A virus (HAV) carrying the HIV gp41
      epitope 2F5.
AB  - Its stable particle structure combined with its high immunogenicity makes the
      hepatitis A virus (HAV) a perfect carrier to expose foreign epitopes to the host
      immune system. In an earlier report [Beneduce, F., Kusov, Y., Klinger, M., Gauss
      Muller, V., Morace, G., 2002. Chimeric hepatitis A virus particles presenting a
      foreign epitope (HIV gp41) at their surface. Antiviral Res. 55, 369-377] chimeric
      virus-like particles (HAV-gp41) were described that carried at their surface the
      dominant gp41 epitope 2F5 (2F5e) of the human immunodeficiency virus HIV-1.
      Extending this work, we now report that chimeric virus HAV-gp41 replicates in HAV
      susceptible cells as well as in non-human primates. Infected marmosets developed
      both an anti-HAV and anti-2F5 epitope immune response. Furthermore, an HIV
      neutralizing antibody response was elicited in guinea pigs immunized with HAV
      gp41 chimeric particles. The results demonstrate that the replication-competent
      chimeric HAV-gp41 can serve as either a live or a subunit vaccine for eliciting
      of antibodies directed against a foreign antigenic epitope.

PMID- 17014914
TI  - IL-18 enhances the migration ability of murine melanoma cells through the
      generation of ROI and the MAPK pathway.
AB  - Interleukin-18 (IL-18) has multiple effects on various cells that are involved in
      immune escape of murine melanoma cells and in the inflammatory responses. This
      study investigated the effect of IL-18 on the ability of murine melanoma cells to
      migrate by using B16F10 cells and the IL-18 antisense transfectants of B16F10
      cells (the B16F10/IL-18 antisense transfectant). The B16F10 cells were more able
      to migrate than were the B16F10/IL-18 antisense transfectants. An exogenous IL-18
      treatment improved the ability of the B16F10/IL-18 antisense transfectant cells
      to migrate, indicating that IL-18 enhanced the migration ability of melanoma
      cells. To determine the signaling mechanisms involved in IL-18-enhanced
      migration, we measured the ROI levels. It was found that the ROI levels were
      increased by IL-18, and an antioxidant, N-acetyl-l-cystein (NAC), blocked the
      effect of IL-18 on migration, suggesting the involvement of ROI in the signal
      transduction of IL-18-enhanced cell migration. IL-18-enhanced cell migration was
      also reduced by PD98059. In addition, the level of ERK1/2 phosphorylation was
      markedly increased by treating with exogenous IL-18 at 20 min. These results
      suggest that IL-18 enhances the ability of melanoma cells to migrate via the
      generation of ROI and the MAPK pathway.

PMID- 17014916
TI  - Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and
      infecting human corneal epithelial cells.
AB  - Adenovirus type 37 is one of the main causative agents of epidemic
      keratoconjunctivitis. In a series of publications, we have reported that this
      virus uses sialic acid as a cellular receptor. Here we demonstrate in vitro that
      on a molar basis, multivalent sialic acid conjugated to human serum albumin
      prevents adenovirus type 37 from binding to and infecting human corneal
      epithelial cells 1000-fold more efficiently than monosaccharidic sialic acid. We
      also demonstrate that the extraordinary inhibitory effect of multivalent sialic
      acid is due to the ability of this compound to aggregate virions. We conclude
      that multivalent sialic acid may be a potential new antiviral drug, for use in
      the treatment of epidemic keratoconjunctivitis caused by the adenoviruses that
      use sialic acid as cellular receptor.

PMID- 17014917
TI  - Over-expression of two different forms of the alpha-secretase ADAM10 affects
      learning and memory in mice.
AB  - Members of the ADAM family (adisintegrin and metalloprotease) are the main
      candidates for physiologically relevant alpha-secretases. The alpha-secretase
      cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the
      region of the Abeta peptides preventing their aggregation in the brain. The
      increase of alpha-secretase activity in the brain provides a plausible strategy
      to prevent Abeta formation. Concerning this possibility two transgenic mouse
      lines (FVB/N) have been created: mice over-expressing the bovine form of the
      alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha
      secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1
      generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared
      to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the
      following tasks: standard open field, enriched open field, elevated plus-maze,
      and the Morris water maze hidden platform task. Concerning basal activity,
      exploration, and anxiety, transgenic mice behaved similar to controls. With
      respect to learning and memory both transgenic lines showed a significant deficit
      compared to controls. ADAM10 mice however, showed thigmotaxis with passive
      floating behavior in the Morris water maze indicating differences in motivation,
      whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed
      search pattern. Thus variation of the enzymatic activity of alpha-secretase
      ADAM10 alters learning and memory differentially. Nevertheless, it could be
      concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the
      assessment of alpha-secretase-related effects in animal models of Alzheimer's
      disease.

PMID- 17014919
TI  - Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects
      mice against acute pancreatitis and associated lung injury.
AB  - Acute pancreatitis is a common, and as yet incurable, clinical condition, the
      incidence of which has been increasing over recent years. Chemokines are believed
      to play a key role in the pathogenesis of acute pancreatitis. We have earlier
      shown that treatment with a neutralizing antibody against CINC, a CXC chemokine,
      protects rats against acute pancreatitis-associated lung injury. The hexapeptide
      antileukinate (Ac-RRWWCR-NH2) is a potent inhibitor of binding of CXC chemokines
      to the receptors (CXCR2). This study aims to evaluate the effect of treatment
      with antileukinate on acute pancreatitis and the associated lung injury in mice.
      Acute pancreatitis was induced in adult male Swiss mice by hourly intra
      peritoneal injections of caerulein (50 microg/kg/h) for 10 h. Antileukinate
      (52.63 mg/kg, s.c.) was administered to mice either 30 min before or 1 h after
      starting caerulein injections. Severity of acute pancreatitis was determined by
      measuring plasma amylase, pancreatic water content, pancreatic myeloperoxidase
      (MPO) activity, pancreatic macrophage inflammatory protein-2 (MIP-2) levels and
      histological examination of sections of pancreas. A rise in lung MPO activity and
      histological evidence of lung injury in lung sections was used as criteria for
      pancreatitis-associated lung injury. Treatment with antileukinate protected mice
      against acute pancreatitis and associated lung injury, showing thereby that anti
      chemokine therapy may be of value in this condition.

PMID- 17014918
TI  - Chloroquine-resistant isoforms of the Plasmodium falciparum chloroquine
      resistance transporter acidify lysosomal pH in HEK293 cells more than chloroquine
      sensitive isoforms.
AB  - The emergence of chloroquine-resistant Plasmodium falciparum malaria imperils the
      lives of millions of people in Africa, Southeast Asia and South America.
      Chloroquine resistance is associated with mutations in the P. falciparum
      chloroquine resistance transporter (PfCRT). We expressed chloroquine-sensitive
      (HB3) and resistant (Dd2) pfcrt alleles in HEK293 human embryonic kidney cells.
      PfCRT localized to the lysosomal limiting membrane and was not detected in the
      plasma membrane. We observed significant acidification of lysosomes containing
      PfCRT HB3 and Dd2, with Dd2 acidifying significantly more than HB3. A mutant HB3
      allele expressing the K76T mutation (earlier found to be key for chloroquine
      resistance) acidified to the same extent as Dd2, whereas the acidification by a
      Dd2 allele expressing the T76K "back mutation" was significantly less than Dd2.
      Thus, the amino acid at position 76 is both an important determinant of
      chloroquine resistance in parasites and of lysosomal acidification following
      heterologous expression. PfCRT may be capable of modulating the pH of the
      parasite digestive vacuole, and thus chloroquine availability. Chloroquine
      accumulation and glycyl-phenylalanine-2-naphthylamide-induced release of
      lysosomal Ca(2+) stores were unaffected by PfCRT expression. Cytoplasmic domain
      mutations did not alter PfCRT sorting to the lysosomal membrane. This
      heterologous expression system will be useful to characterize PfCRT protein
      structure and function, and elucidate its molecular role in chloroquine
      resistance.

PMID- 17014920
TI  - Connexin mRNA expression in single dopaminergic neurons of substantia nigra pars
      compacta.
AB  - Dopaminergic neurons of the substantia nigra pars compacta play a major role in
      goal-directed behavior and reinforcement learning. The study of their local
      interactions has revealed that they are connected by electrical synapses.
      Connexins, the molecular substrate of electrical synapses, constitute a
      multigenic family of 20 proteins in rodents. The permeability and regulation
      properties of electrical synapses depend on their connexin composition.
      Therefore, the knowledge of the molecular composition of electrical synapses is
      fundamental to the understanding of their specific functions. We have
      investigated the connexin mRNA expression pattern of dopaminergic neurons by
      single-cell RT-PCR analysis, during two periods in which dopaminergic neurons are
      electrically coupled in vitro (P7-P10 and P17-P21). Our results show that
      dopaminergic neurons express mRNAs of various connexins (Cx26, Cx30, Cx31.1,
      Cx32, Cx36 and Cx43) in a developmentally regulated manner. Furthermore, we have
      observed that dopaminergic neurons display different connexin expression
      patterns, and that multiple connexins can be expressed in a single dopaminergic
      neuron. These observations underline the importance of electrical coupling in the
      development of dopaminergic neurons and raise the question of the existence of
      functionally distinct electrically coupled networks in the substantia nigra pars
      compacta.

PMID- 17014921
TI  - An expanded Fermi solution for microbial risk assessment.
AB  - 'Fermi solution' refers to an estimate of a quantity of interest derived from a
      sequence of guesses about factors of which detailed knowledge is unavailable.
      When one makes such guesses, it is unlikely that the large majority of them will
      be either too high or too low. Most probably, some of the overestimates will be
      offset by some of the underestimates, and the final result will be often close to
      the correct value. The method has been popularized as recreational physics but it
      has also been applied in risk assessment, where the factors involved, but not
      their exact magnitudes, are known. The concept has potential application in
      certain types of food poisoning risk assessments, and in estimating the number
      victims of a bioterrorist attack on the food or water supply, where some guessing
      is inevitable because of the absence of accurate relevant data. We consider a
      version of the method in which ranges instead of single values are entered as the
      factors' estimates. For simplicity, the risk to be assessed is taken to be the
      product of the factors, and their true values are regarded as being uniformly
      distributed over their respective ranges. The risk itself is therefore construed
      as a random variable with a probability distribution whose parameters are
      explicitly determined by the individual factors' ranges and which can often be
      approximated by a lognormal distribution. The mode of this lognormal distribution
      is taken to be the "best guess" of the risk, and a credible interval is
      constructed with a specified level of "confidence". The best guess and credible
      interval are shown to be robust against small perturbations of the ranges. Thus,
      even if the ranges are misspecified to some degree, assessments based on the best
      guess or credible interval will not be substantially altered. This can help to
      achieve consensus among assessors in situations where very little hard knowledge
      exists. The calculation procedure has been automated in software that has been
      made freely available over the Internet. The concept is demonstrated with two
      hypothetical problems: predicting the number of persons who would come down with
      acute food poisoning after consuming a contaminated dish, and estimating the
      number of daily salmonellosis cases in a large metropolitan area.

PMID- 17014922
TI  - Occurrence of pathogenic fungal species in Tunisian vineyards.
AB  - Mycotoxins are secondary metabolites produced by filamentous fungi detected in
      food, such are grapes. OTA was evaluated in ten handle musts from different
      Tunisian vineyard. This mycotoxin was found at levels 1.1 mug/L to 4.3 mug/L. A
      survey was conducted to assess the contamination of the Tunisian vineyard with
      pathogenic fungal species, in particular those responsible of the OTA production.
      The results were evaluated for the first time in parcels cultivated in the North,
      in the Centre and in the South of the country. Italia Muscate and Superior
      Seedless varieties were concerned at three developmental stages of the berry,
      setting, veraison and maturity. Carigon variety was used as positive control for
      musts contaminating by OTA. The main fungal species isolated were Aspergillus
      spp. (33.32%), Botrytis cinerea (23.32%), Alternaria spp. (12.80%), Cladosporium
      spp. (10.59%) and Penicillium spp. (8.3%). The isolates of the Aspergillus genus
      were identified as Aspergillus niger aggregate (77%), Aspergillus carbonarius
      (15%) and Aspergillus flavus (8%). Their presence was characterized by a
      significant decrease in the Centre during the veraison and a slight increase in
      the North and the South during the maturity stage. Furthermore, when comparing
      Superior Seedless and Italia Muscate cultivated in the same area, the aspergilli
      were particularly less abundant at the setting stage in the case of Superior
      Seedless. There is no correlation between the OTA amount in musts and the
      contamination by Aspergillus species in different vineyards and for grape
      varieties studied.

PMID- 17014923
TI  - In vitro cell fusion between CD4(+) and HIV-1 Env(+) T cells generates a
      diversity of syncytia varying in total number, size and cellular content.
AB  - Syncytia formation in HIV infections is driven by the virus fusion-active
      molecules (Env) interacting with membrane components of hosts cells. HIV-syncytia
      are usually interpreted as pathogenic entities and although they may potentially
      vary in size, numbers and types of constituent cells, little is known about the
      extent and significance of their diversity. Here, we describe numerically the
      cell population dynamics and the diversity of syncytia produced in the in vitro
      cell-fusion between two Jurkat T cell lines, one CD4(+) and the other Env(+).
      Cell-fusion partners were differentially stained with the lipophilic DiI and DiO,
      or with the cytoplasmic CMFDA and CMTMR tracers and syncytia showing double
      fluorescence were counted in a flow cytometer. The total number of syncytia
      formed, their size, cellular complexity and ratio of CD4(+)/Env(+) cells
      recruited, varied significantly in relation with time of reaction and initial
      proportions of fusion partners. The considerable structural diversity of syncytia
      formed, in so limited an in vitro cell fusion reaction, suggests that a greater
      heterogeneity may be formed in the natural course of disease. Identification of
      the main determinants of syncytia diversity allows for a detailed study of the
      relation between the syncytia structure and function.

PMID- 17014924
TI  - Transforming growth factor-beta 1 levels in women with prior history of
      gestational diabetes mellitus.
AB  - It is known that women with prior history of gestational diabetes mellitus (pGDM)
      feature obesity, insulin resistance and endothelial dysfunction which cause
      premature atherosclerosis. Transforming growth factor-beta 1 (TGF-beta1) is a key
      cytokine in obesity and insulin resistance and also play important roles in the
      development of atherosclerosis. This study was conducted to demonstrate the serum
      TGF-beta1 levels of people with pGDM. Thirty women with pGDM, 20 women with type
      2 diabetes mellitus (T2DM) and 20 healthy women were enrolled. Serum TGF-beta1
      levels of people with pGDM were found to be significantly higher than healthy
      controls and significantly lower than women with T2DM. TGF-beta1 levels were
      found to be correlated with postprandial glucose and age and inversely correlated
      with body mass index (BMI) and waist circumference. On multiple regression
      analysis postprandial glucose level, age and BMI were determined as the most
      important factors affecting TGF-beta1 levels. This study demonstrates elevated
      TGF-beta1 levels in pGDM. The inflammatory response to hyperglycemia and insulin
      resistance could be the major factors for the increased expression of TGF-beta1.

PMID- 17014925
TI  - Polymorphisms in the FAS and FASL genes and risk of lung cancer in a Korean
      population.
AB  - BACKGROUND: The FAS and FASL system play an important role in regulating
      extrinsic apoptotic pathway and inappropriate regulation of this signaling
      pathway contributes to lung tumorigenesis. Polymorphisms in the promoter region
      of the FAS (-1377G>A and -670A>G) and FASL (-844C>T) have been shown to alter the
      transcriptional activities of these genes. In order to evaluate the contribution
      of these polymorphisms to the risk of lung cancer, we carried out a case-control
      study in a Korean population. METHODS: The FAS and FASL genotypes were determined
      in 582 lung cancer patients and 582 healthy control subjects who were frequency
      matched for age and gender. RESULTS: The FAS and FASL genotypes and the FAS
      haplotypes exhibited no apparent relationship with the risk of lung cancer. In
      addition, there was no significant interaction between the FAS and FASL
      polymorphisms in the development of lung cancer. CONCLUSION: These results
      suggest that the FAS-1377G>A and -670A>G and FASL-844C>T polymorphisms do not
      significantly affect the susceptibility to lung cancer in Koreans.

PMID- 17014926
TI  - A partially coupled, fraction-by-fraction modelling approach to the subsurface
      migration of gasoline spills.
AB  - The subsurface spreading behaviour of gasoline, as well as several other common
      soil- and groundwater pollutants (e.g. diesel, creosote), is complicated by the
      fact that it is a mixture of hundreds of different constituents, behaving
      differently with respect to e.g. dissolution, volatilisation, adsorption and
      biodegradation. Especially for scenarios where the non-aqueous phase liquid
      (NAPL) phase is highly mobile, such as for sudden spills in connection with
      accidents, it is necessary to simultaneously analyse the migration of the NAPL
      and its individual components in order to assess risks and environmental impacts.
      Although a few fully coupled, multi-phase, multi-constituent models exist, such
      models are highly complex and may be time consuming to use. A new, somewhat
      simplified methodology for modelling the subsurface migration of gasoline while
      taking its multi-constituent nature into account is therefore introduced here.
      Constituents with similar properties are grouped together into eight fractions.
      The migration of each fraction in the aqueous and gaseous phases as well as
      adsorption is modelled separately using a single-constituent multi-phase flow
      model, while the movement of the free-phase gasoline is essentially the same for
      all fractions. The modelling is done stepwise to allow updating of the free-phase
      gasoline composition at certain time intervals. The output is the concentration
      of the eight different fractions in the aqueous, gaseous, free gasoline and solid
      phases with time. The approach is evaluated by comparing it to a fully coupled
      multi-phase, multi-constituent numerical simulator in the modelling of a typical
      accident-type spill scenario, based on a tanker accident in northern Sweden. Here
      the PCFF method produces results similar to those of the more sophisticated,
      fully coupled model. The benefit of the method is that it is easy to use and can
      be applied to any single-constituent multi-phase numerical simulator, which in
      turn may have different strengths in incorporating various processes. The results
      demonstrate that the different fractions have significantly different migration
      behaviours and although the methodology involves some simplifications, it is a
      considerable improvement compared to modelling the gasoline constituents
      completely individually or as one single mixture.

PMID- 17014927
TI  - Pilot study to evaluate the accuracy of ultrasonography in confirming
      endotracheal tube placement.
AB  - STUDY OBJECTIVE: Visualization of the vocal cords and end-tidal capnography are
      the usual standards in confirming endotracheal tube placement. Vocal cord
      visualization is, however, not always possible, and capnography is not 100%
      reliable and requires ventilation of the lungs to confirm placement. The goal of
      this study is to determine the accuracy of ultrasonography for detecting
      endotracheal tube placement into the trachea and esophagus in real time. METHODS:
      This was a prospective, randomized, controlled study. Eligible patients were
      adults undergoing elective surgery requiring intubation. Exclusion criteria were
      a history of difficult intubation, abnormal airway anatomy, aspiration risk
      factors, and esophageal disease. Thirty-three patients were enrolled. After
      induction of anesthesia and neuromuscular blockade, the anesthesiologist placed
      the endotracheal tube in the trachea and esophagus in random order with direct
      laryngoscopy. During the intubations, a high-frequency, linear transducer was
      placed transversely on the neck at the suprasternal notch. Two emergency
      physicians, blinded to the order and performance of the intubations,
      independently recorded the location of the endotracheal tube according to the
      real-time ultrasonographic image. A 2-by-2 table was used to calculate
      sensitivity and specificity of the emergency physicians' ability to detect
      placement of the endotracheal tube. RESULTS: For each physician, the sensitivity
      for identifying the first intubation as tracheal was 100% (95% confidence
      interval [CI] 77% to 100%) with a specificity of 100% (95% CI 82% to 100%). One
      endotracheal tube was unintentionally placed twice in the esophagus, but both
      tube placements were identified as esophageal by the emergency physicians.
      CONCLUSION: In this pilot study, 2 emergency physicians experienced in
      ultrasonography accurately detected placement of endotracheal tubes during
      intubation with ultrasonography in select patients in the controlled environment
      of the operating room. Future studies should examine the use of ultrasonography
      to visualize endotracheal tube placement in real time by emergency physicians
      with less ultrasonographic training; use of the technique in the emergency
      department on a wider range of patients, including patients with difficult
      airways; and assessment of the utility of ultrasonography in confirmation of
      endotracheal tube position in already intubated patients.

PMID- 17014928
TI  - The Internet Tracking Registry of Acute Coronary Syndromes (i*trACS): a
      multicenter registry of patients with suspicion of acute coronary syndromes
      reported using the standardized reporting guidelines for emergency department
      chest pain studies.
AB  - STUDY OBJECTIVE: Observational studies of well-described patient populations
      presenting to emergency departments (EDs) with suspicion of acute coronary
      syndrome are necessary to understand the relationships between patients' signs
      and symptoms, cardiac risk profile, test results, practice patterns, and
      outcomes. We describe the methods for data collection and the ED population
      enrolled in a multicenter registry of patients with chest pain. METHODS: Patients
      older than 18 years, presenting to one of 8 EDs in the United States or 1 ED in
      Singapore, and with possible acute coronary syndrome were enrolled in the
      Internet Tracking Registry of Acute Coronary Syndromes between June 1999 and
      August 2001. Prospective data, including presenting signs and symptoms, ECG
      findings, and the ED physician's initial impression of risk, were systematically
      collected. Medical record review or daily follow-up was used to obtain cardiac
      biomarker results, invasive and noninvasive testing, treatments, procedures, and
      inhospital outcomes. Thirty-day outcomes were determined by telephone follow-up
      and medical record review. RESULTS: The registry includes 15,608 patients, with
      17,713 visits. Chest pain was the chief complaint in 71% of visits. The ECG was
      diagnostic of ischemia or infarction in 10.1% and positive cardiac biomarkers
      were observed in 10% of visits. Forty-three percent of patients were sent home
      directly from the ED. Of admitted patients, 5% died by 30 days, and 3% had
      documented coronary artery disease or had undergone percutaneous coronary
      intervention or coronary artery bypass grafting within 30 days. For patients
      discharged directly from the ED, 0.4% died or had a documented myocardial
      infarction within 30 days. Coronary artery bypass graft surgery, percutaneous
      coronary intervention, or a diagnosis of coronary artery disease was found in
      0.5% of discharged patients. CONCLUSION: A unique description of undifferentiated
      ED chest pain patients with suspected acute coronary syndrome is provided. The
      data set can be used to generate and explore hypotheses to improve understanding
      of the complex relationships between presentation, treatment, testing,
      intervention and outcomes.

PMID- 17014929
TI  - The 2003 model of the clinical practice of emergency medicine: the 2005 update.

PMID- 17014930
TI  - Norepinephrine acts as D1-dopaminergic agonist in the embryonic avian retina:
      late expression of beta1-adrenergic receptor shifts norepinephrine specificity in
      the adult tissue.
AB  - Dopamine is the main catecholamine found in the chick retina whereas
      norepinephrine is only found in trace amounts. We compared the effectiveness of
      dopamine and norepinephrine in promoting cyclic AMP accumulation in retinas at
      embryonic day 13 (E13) and from post-hatched chicken (P15). Dopamine
      (EC(50)=10microM) and norepinephrine (EC(50)=30microM), but not the beta(1)
      adrenergic agonist isoproterenol, stimulated over seven-fold the production of
      cyclic AMP in E13 retina. The cyclic AMP accumulation induced by both
      catecholamines in embryonic tissue was entirely blocked by 2microM SCH23390, a
      D(1) receptor antagonist, but not by alprenolol (beta-adrenoceptor antagonist).
      In P15 retinas, 100microM isoproterenol stimulated five-fold the accumulation of
      cAMP. This effect was blocked by propanolol (10microM), but not by 2microM
      SCH23390. Embryonic and adult retina display beta(1) adrenergic receptor mRNA as
      detected by RT-PCR, but the beta(1) adrenergic receptor protein was detected only
      in post-hatched tissue. We conclude that norepinephrine cross-reacts with D(1)
      dopaminergic receptor with affinity similar to that of dopamine in the embryonic
      retina. In the mature retina, however, D(1) receptors become restricted to
      activation by dopamine. Moreover, as opposed to the embryonic tissue,
      norepinephrine seems to stimulate cAMP accumulation via beta(1)-like adrenergic
      receptors in the mature tissue.

PMID- 17014931
TI  - Patients' views of nurses' competence.
AB  - This study examines, from the patients' perspective, what is meant by competent
      nursing and how, with this perspective in mind, patients would view the prospect
      of assessing the competence of nurses. There is a little empirical research that
      clarifies professional competence from the patient's perspective. Nursing
      curricula in the UK have shifted attention to 'competencies' as the outcome of
      nurse education and, in an era of patient involvement, their views are important
      to investigate. The study utilises a grounded theory approach. Data were
      collected in Central Scotland between 2001 and 2003. Twenty-seven patients
      participated. Data were analysed, in keeping with the grounded theory tradition,
      utilising the constant comparative method. Patients described the foundation of
      competent nursing practice as technical care and nursing knowledge. Patients
      assume that technical care is competent as safe guards are considered to be in
      place to protect patients. When technical competence is assumed, interpersonal
      attributes become the most important indicator of the quality of nursing care.
      The results of this study highlight uncertainty about whether patients feel able
      to assess the competence of nurses. The results of this study may have
      implications for nurses internationally when trying to involve patients in the
      assessment of nurses.

PMID- 17014932
TI  - The frequency of item writing flaws in multiple-choice questions used in high
      stakes nursing assessments.
AB  - Multiple-choice questions are a common assessment method in nursing examinations.
      Few nurse educators, however, have formal preparation in constructing multiple
      choice questions. Consequently, questions used in baccalaureate nursing
      assessments often contain item-writing flaws, or violations to accepted item
      writing guidelines. In one nursing department, 2770 MCQs were collected from
      tests and examinations administered over a five-year period from 2001 to 2005.
      Questions were evaluated for 19 frequently occurring item-writing flaws, for
      cognitive level, for question source, and for the distribution of correct
      answers. Results show that almost half (46.2%) of the questions contained
      violations of item-writing guidelines and over 90% were written at low cognitive
      levels. Only a small proportion of questions were teacher generated (14.1%),
      while 36.2% were taken from testbanks and almost half (49.4%) had no source
      identified. MCQs written at a lower cognitive level were significantly more
      likely to contain item-writing flaws. While there was no relationship between the
      source of the question and item-writing flaws, teacher-generated questions were
      more likely to be written at higher cognitive levels (p<0.001). Correct answers
      were evenly distributed across all four options and no bias was noted in the
      placement of correct options. Further training in item-writing is recommended for
      all faculty members who are responsible for developing tests. Pre-test review and
      quality assessment is also recommended to reduce the occurrence of item-writing
      flaws and to improve the quality of test questions.

PMID- 17014933
TI  - RN as gatekeeper: student understanding of the RN buddy role in clinical practice
      experience.
AB  - Students may be informally buddied with registered nurses (RNs), during their
      clinical experience. This paper describes one component of a larger
      phenomenographic study that explored the qualitatively different ways students
      understand the RN buddy role during clinical experience and the implications of
      this understanding for student learning. The perception of the RN as gatekeeper
      was an unexpected finding and is the focus of this report. Phenomenography is a
      field of descriptive research concerned with the variation in ways people
      experience and understand similar phenomena. This approach was used to identify
      the variation in experience and understanding of students with buddy RNs.
      Individual semi-structured interviews were conducted with a purposive sample of
      24 students from one university in Queensland, Australia. The two variations in
      understanding of the role discussed in this paper are: understanding as an
      expectation, and RN as gatekeeper: gatekeeping as access. The research highlights
      that the various ways RNs promote or block access for students influence the
      quality of the learning experience. Formal recognition of the complexity of the
      RN role is essential to ensure RNs have adequate preparation for their role with
      students.

PMID- 17014934
TI  - High tech cheating.
AB  - The use of technology has enhanced the convenience, flexibility, and efficiency
      of both preparatory and continuing education. Unfortunately, academic dishonesty,
      including plagiarism, has shown a positive correlation with the increased use of
      technology in education. A review of the literature related to unintended
      outcomes of the use of technology in nursing education and continuing education
      was conducted to determine the ethical implications for the nursing profession.
      Although nursing research dealing with academic and professional misconduct is
      sparse, evidence suggests that academic dishonesty is a predictor of workplace
      dishonesty. Given this correlation between unethical classroom behavior and
      unethical clinical behavior, efforts to staunch academic dishonesty may help
      allay professional misconduct. A combination of high tech and low tech methods
      may be used to minimize unethical behaviors among students and practicing
      professional nurses in order to maintain the integrity of the profession.

PMID- 17014935
TI  - Potentiation of the immune response to non-adsorbed antigens by aluminum
      containing adjuvants.
AB  - The degree of antigen adsorption by aluminum-containing adjuvants is considered
      an important characteristic of vaccines that is related to immunopotentiation by
      the adjuvant. This study examined immunopotentiation by aluminum phosphate
      adjuvant in three model vaccines in which the antigen was not adsorbed in the
      vaccine formulation nor when mixed in vitro with interstitial fluid. In the first
      model vaccine, aluminum phosphate adjuvant was pre-treated with 0.5 M KH2PO4 to
      minimize the adsorption of dephosphorylated alpha casein. The second model
      vaccine was composed of aluminum phosphate adjuvant and ovalbumin that was
      dephosphorylated by treatment with potato acid phosphatase. The third model
      vaccine consisted of aluminum phosphate adjuvant and lysozyme (LYS). In order to
      prevent adsorption of lysozyme, the aluminum phosphate adjuvant was pre-treated
      with fibrinogen, a protein present in interstitial fluid that binds strongly to
      aluminum phosphate adjuvant. Immunopotentiation was evaluated by measuring
      antibody production in mice. It was found that all three model vaccines induced
      antibody titers that were statistically higher than induced by a solution of
      antigen without adjuvant and similar to vaccines in which the antigens were
      adsorbed by aluminum phosphate adjuvant. Confocal microscopy experiments
      suggested that the antigens used in these experiments, even though not adsorbed
      to the aluminum phosphate adjuvant, were trapped in void spaces within the
      adjuvant aggregates, resulting in uptake of antigen by dendritic cells.

PMID- 17014936
TI  - Assessment of the monoterpene, glycidic and triterpene-moieties' contributions to
      the adjuvant function of the CP05 saponin of Calliandra pulcherrima Benth during
      vaccination against experimental visceral leishmaniasis.
AB  - The CP05 saponin from Calliandra pulcherrima Benth, shows remarkable similarities
      to the QS21 saponin of Quillaja saponaria Molina. Both shared a monoterpene
      hydrophobic moiety, a glycidic chain attached to the triterpene C28, and three
      sugars attached to C3. Different from QS21, the CP05 does not show the aldehyde
      group in triterpene C4 involved in TH1 response. Balb/c mice were immunized
      either intact saponin (CP05), the monoterpene-deprived (BS), the C28 carbohydrate
      deprived (HS) or the sapogenin fraction, in formulation with the FML antigen of
      Leishmania donovani and challenged with 2 x 10(8) amastigotes of L. chagasi.
      While the CP05 induced 90% survival and 92.1% parasite reduction, a 100% survival
      and 94.1% protection were detected after the BS-vaccine treatment, indicating
      that the monoterpene acylated moiety, absent in the BS vaccine, is not necessary
      for the induction of a protective global TH1 response. Only the DTH response of
      BS vaccines was mildly lower than that of CP05 vaccinees. Maximal anti-FML
      antibody, CD4(+) and CD8(+) Leishmania specific lymphocytes, IFN-gamma splenocyte
      secretion, reduction in parasite load and survival was also detected for the BS
      vaccine. The HSFML vaccine showed diminished responses in all tested variables,
      except for IFN-gamma secretion, indicating that the integrity of the carbohydrate
      moiety attached to C28 is mandatory for the these functions. No protection was
      induced by the sapogenin-FML indicating that the CP05 triterpene which lacks the
      C4 aldehyde group, is not a immunostimulating compound. No contribution to
      protection was detected in the CP05 saponin treated control group supporting the
      specificity of the FML antigenic preparation.

PMID- 17014937
TI  - Role of T lymphocyte replicative senescence in vaccine efficacy.
AB  - Immunological changes associated with aging play a major role in both the blunted
      responses to infections as well as to vaccines intended to prevent many of these
      infections. Several independent studies on immune correlates of poor vaccine
      responsiveness have identified a novel immune biomarker of reduced antibody
      response to vaccination, namely high proportions of memory CD8 T lymphocytes
      lacking expression of the CD28 costimulatory molecule. Research on this
      population of CD8(+)CD28(-) T lymphocytes has documented characteristics
      suggestive of replicative senescence, including inability to proliferate, reduced
      telomere length, and altered cytokine profiles. CD8(+)CD28(-) T lymphocytes have
      also been associated with suppressor functions and with early mortality in the
      elderly. This article discusses some of the challenges involved in custom
      designing vaccines for the elderly, and suggests several immunomodulatory
      strategies that may enhance vaccine responsiveness in this age group.

PMID- 17014938
TI  - Exposure of Ugandan health personnel to measles and rubella: evidence of the need
      for health worker vaccination.
AB  - With rubella and, until recently, measles highly endemic in Uganda, health
      personnel are at risk of these vaccine-preventable diseases and a source of
      transmission to patients. Measles and rubella serology (IgG) and history of
      exposure and vaccination were determined among 311 health care workers in a
      nationwide study. All tested positive for measles IgG, whereas 49.2% reported
      having been vaccinated. Rubella antibodies were present in 98.1% of personnel;
      3.2% of women of child-bearing age were still susceptible. Increasing age and
      longer duration of service increased the risk of rubella infection. A national
      policy on health worker protection should include immunisation against vaccine
      preventable diseases upon entry to training.

PMID- 17014940
TI  - Particle size distribution and PAH concentrations of incense smoke in a
      combustion chamber.
AB  - The particle size distribution and the concentrations of polycyclic aromatic
      hydrocarbons (PAHs) in incense smoke were studied using a custom-designed
      combustion chamber. Among the nine types of incense investigated, the particle
      and the total PAH emission factors varied significantly. The average mass median
      aerodynamic diameter (MMAD) of the smoke aerosol was 262+/-49nm, which positively
      correlated to particle emission factor (mg/stick, p<0.05). Coagulation was a
      major mechanism that dictates the MMAD of the smoke. The total toxic equivalency
      (the sum of the benzo[a]pyrene equivalent concentration) of the solid-phase PAHs
      (S-PAHs) was over 40 times higher than that of the corresponding gas-phase PAHs,
      indicating that the S-PAHs in incense smoke may pose potential health risk.
      Experiments show that each lowered percentage of total carbon content in the raw
      incense helped decrease the particle emission factor by 2.6mg/g-incense, and the
      reduction of S-PAH emission factor ranged from 8.7 to 26% when the carbon content
      was lowered from 45 to 40%.

PMID- 17014939
TI  - Immune responses to vaccinia and influenza elicited during primary versus recent
      or distant secondary smallpox vaccination of adults.
AB  - The kinetics and frequency of the primary response to human smallpox vaccine was
      compared to that among subjects re-vaccinated within the last 2 years, or after
      several decades. Vaccination induced local and systemic reactions that were
      mildest in the distant cohort and more severe in the primary vaccinees. The
      timing of IFN-gamma responses was similar in all three groups, but of higher
      frequency in the primary vaccinees. Responses to vaccinia re-immunization between
      those immunized <2 years ago and those immunized >10 years ago were not
      significantly different. Neutralizing antibodies were boosted in all groups, with
      the highest titers observed among the distant cohort. However, the antibody and
      IFN-gamma responses did not correlate strongly with the local reactions at the
      vaccine site. This suggests that local immune events in the tissue are distinct
      from the parameters measured in the peripheral blood.

PMID- 17014941
TI  - Heavy metal concentrations in soils and plant accumulation in a restored
      manganese mineland in Guangxi, South China.
AB  - Heavy metal contamination of metal-mined soils is a widespread problem in China.
      In the restored (over 20 years) Lipu manganese mineland, 36 plant species from 22
      families were found colonizing, some of which were planted agronomic ones. Heavy
      metal concentrations in tailings were very high. Minesoils were basically
      unpolluted, but soils in the remaining mining area and in the vicinity of
      tailings dumps were polluted by Cd and Mn. Measurements of metal contents in
      dominant plants showed they were close to those of other mineland plants. Plants
      tended to have a higher Cd accumulation (as reflected by Biological Accumulation
      Coefficient) from soil, but have a higher Mn translocation (as indicated by
      Biological Transfer Coefficient) to aboveground parts. The Chinese chestnut and
      sugarcane cultivated on the reclaimed mineland were not safe for human
      consumption, and this agricultural restoration pattern should be carefully
      reconsidered.

PMID- 17014942
TI  - The functions of deliberate self-injury: a review of the evidence.
AB  - Deliberate self-injury is defined as the intentional, direct injuring of body
      tissue without suicidal intent. The present article reviews the empirical
      research on the functions of self-injury. This literature includes self-reports
      of reasons for self-injuring, descriptions of the phenomenology of self-injury,
      and laboratory studies examining the effects of self-injury proxies on affect and
      physiological arousal. Results from 18 studies provide converging evidence for an
      affect-regulation function. Research indicates that: (a) acute negative affect
      precedes self-injury, (b) decreased negative affect and relief are present after
      self-injury, (c) self-injury is most often performed with intent to alleviate
      negative affect, and (d) negative affect and arousal are reduced by the
      performance of self-injury proxies in laboratory settings. Studies also provide
      strong support for a self-punishment function, and modest evidence for anti
      dissociation, interpersonal-influence, anti-suicide, sensation-seeking, and
      interpersonal boundaries functions. The conceptual and empirical relationships
      among the different functions remain unclear. Future research should address the
      measurement, co-variation, clinical correlates, and treatment implications of
      different functions.

PMID- 17014943
TI  - Measuring dimensions of social capital: evidence from surveys in poor communities
      in Nicaragua.
AB  - A dominant perspective in social capital research emphasizes a "structural"
      dimension of social capital, consisting of network connections, and a "cognitive"
      dimension, consisting of attitudes toward trust. Correspondingly, membership in
      organizations (i.e., membership density) and general trust in people (i.e.,
      social trust) are two indicators commonly used to relate structural and cognitive
      social capital, respectively, to a variety of health and other outcomes. This
      study analyzed relationships between membership density, social trust and a more
      comprehensive set of household-level social capital indicators as well as
      selected civic and health behaviors in the context of Nicaragua. The sample of
      respondents was drawn from 6 communities and interviews were conducted with 482
      heads of households, resulting in data on 2882 individuals. Factor analyses
      suggest that membership density loaded strongly (loading=0.81) onto an
      "organizational participation" factor which contained a number of qualitative
      characteristics of involvement, including bridging social capital. Further, this
      structural dimension of social capital appears to be a construct consisting of
      more than just informal social networks. However, factor analyses suggest that
      distinctions between levels of trust are warranted in Nicaragua: social trust
      loaded weakly (loading=0.32) onto a factor characterized by institutional trust
      in a factor analysis of trust items, and well below 0.30 in a factor analysis of
      both structural and cognitive dimensions of social capital. A nuanced
      understanding of these household-level indicators of structural and cognitive
      social capital held implications for civic and health behaviors. While membership
      density and institutional trust were positively related to an index of political
      engagement, social trust was either not related or negatively associated (among
      urban respondents). Similarly, social trust was associated with over 50% reduced
      odds of an additional childhood vaccinations whereas institutional trust was
      associated with increased odds (OR=1.7) of an additional vaccination. The
      findings highlight the complexity of social capital and the importance of
      exploring more comprehensive indicators.

PMID- 17014944
TI  - Horizontal equity in health care utilization evidence from three high-income
      Asian economies.
AB  - This paper compares the extent to which the principle of "equal treatment for
      equal need"(ETEN) is maintained in the health care delivery systems of Hong Kong,
      South Korea and Taiwan. Deviations in the degree to which health care is
      distributed according to need are measured by an index of horizontal inequity.
      Income-related inequality in utilization is split into four major sources: (i)
      direct effect of income; (ii) need indicators (self-assessed health status,
      activity limitation, and age and gender interaction terms); (iii) non-need
      variables (education, work status, private health insurance coverage, employer
      provided medical benefits, Medicaid status (low-income medical assistance),
      geographic region and urban/rural residency and (iv) a residual term. Service
      types studied include western doctor, licensed traditional medicine practitioner
      (LTMP), dental and emergency room (ER) visits, as well as inpatient admissions.
      Violations of the ETEN principle are observed for physician and dental services
      in Hong Kong . There is pro-rich inequity in western doctor visits. Unusually,
      this inequity exists for general practitioner but not specialist care. In
      contrast, South Korea appears to have almost comprehensively maintained ETEN
      although the better-off have preferential access to higher levels of outpatient
      care. Taiwan shows intermediate results in that the rich are marginally more
      likely to use outpatient services, but quantities of western doctor and dental
      visits are evenly distributed while there is modest pro-rich bias in the number
      of LTMP episodes. ER visits and inpatient admissions in Taiwan are either
      proportional or slightly pro-poor. Future work should focus on the evaluation of
      policy interventions aimed at reducing the observed unequal distributions.

PMID- 17014945
TI  - Variant Creutzfeldt-Jakob disease and the Canadian blood system after the tainted
      blood tragedy.
AB  - The transfusion transmission of hepatitis C and HIV to thousands of Canadian
      blood recipients was one of this country's largest public health catastrophes. In
      response to this crisis, and in an effort to prevent such a tragedy from
      occurring again, the Canadian blood system has undergone substantial reform.
      Variant Creutzfeldt-Jakob (vCJD) disease was the first infectious threat faced by
      the blood system since undergoing reform. The response at the time to this risk
      provides insights into the Canadian blood system's new approach to infectious
      threats. Our analysis of the decision-making concerning vCJD identifies two
      dominant themes characterizing the new blood system's approach to safety: (1) the
      adoption of a precautionary approach to new risks which involves taking action in
      advance of definitive evidence, and (2) risk aversion amongst policy makers,
      which has contributed to the adoption of safety measures with comparatively high
      cost-effectiveness ratios. Overall the principles governing the new blood system
      have contributed to the system both providing protection against emerging
      infectious risks and regaining the confidence of the public and recipients.
      However, the current set of policy factors will likely contribute to increasingly
      risk-averse policy making that will contribute to continued increases in the cost
      of the blood system. The challenge the blood system now faces is to find the
      appropriate balance between maximizing safety and ensuring the system remains
      affordable.

PMID- 17014946
TI  - "We're tired, not sad": benefits and burdens of mothering a child with a
      disability.
AB  - Caregiver burden has received considerable emphasis in the literature on the
      social experience of mothering children with disabilities. Little attention has
      been paid, however, to either the nature of the burdens perceived or to maternal
      ability to see beyond the burdens to the benefits of their caregiving role. This
      study utilizes a mixed methods approach to examine these neglected aspects of the
      social experience of mothering children with disabilities. Findings of a survey
      of 81 mothers of children with disabilities in Florida, USA and follow-up
      interviews with 7 of these mothers indicate that: 1. For most of the mothers
      included in the study, "the burden of care" is a matter of socio-structural
      constraints (Objective Burden) rather than emotional distress (Subjective
      Burden); 2. Despite the socio-structural constraints associated with caring for a
      child with complex needs, most mothers perceive valuable benefits in having a
      child with a disability; and 3. Perceived Stigma has an important positive impact
      on both dimensions of burden and, through its impact on Subjective Burden, can
      decrease the perceived benefits of caring for a child with a disability.

PMID- 17014947
TI  - [Percutaneous treatment of cystic lymphangiomas].
AB  - Management of cystic lymphangioma necessitate for optimal diagnosis and treatment
      the expertise of a trained multidisciplinary team including dermatologists,
      radiologists, plastic and vascular surgeons. An initial imaging work-up of these
      lesions by ultrasound Doppler examination and MR imaging are necessary before
      treatment planning. Depending of the size, the location, the risk for the
      adjacent organs, a therapeutic decision may be mandatory. Percutaneous
      sclerotherapy is a safe and efficient treatment. It is the treatment of choice
      that must be proposed in first intention.

PMID- 17014948
TI  - Molecular pathological analysis for determining the possible mechanism of
      piperonyl butoxide-induced hepatocarcinogenesis in mice.
AB  - Piperonyl butoxide (PBO), alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylene-dioxy-2
      propyltoluene, is widely used as a synergist for pyrethrins. In order to clarify
      the possible mechanism of non-genotoxic hepatocarcinogenesis induced by PBO,
      molecular pathological analyses consisting of low-density microarray analysis and
      real-time reverse transcriptase (RT)-PCR were performed in male ICR mice fed a
      basal powdered diet containing 6000 or 0 ppm PBO for 1, 4, or 8 weeks. The
      animals were sacrificed at weeks 1, 4, and 8, and the livers were
      histopathologically examined and analyzed for gene expression using the
      microarray at weeks 1 and 4 followed by real-time RT-PCR at each time point.
      Reactive oxygen species (ROS) products were also measured using liver microsomes.
      At each time point, the hepatocytes of PBO-treated mice showed centrilobular
      hypertrophy and increased lipofuscin deposition in Schmorl staining. The ROS
      products were significantly increased in the liver microsomes of PBO-treated
      mice. In the microarray analysis, the expression of oxidative and metabolic
      stress-related genes--cytochrome P450 (Cyp) 1A1, Cyp2A5 (week 1 only), Cyp2B9,
      Cyp2B10, and NADPH-cytochrome P450 oxidoreductase (Por) was over-expressed in
      mice given PBO at weeks 1 and 4. Fluctuations of these genes were confirmed by
      real-time RT-PCR in PBO-treated mice at each time point. In additional real-time
      RT-PCR, the expression of Cyclin D1 gene, key regulator of cell-cycle
      progression, and Xrcc5 gene, DNA damage repair-related gene, was significantly
      increased at each time point and at week 8, respectively. These results suggest
      the possibility that PBO has the potential to generate ROS via the metabolic
      pathway and to induce oxidative stress, including oxidative DNA damage, resulting
      in the induction of hepatocellular tumors in mice.

PMID- 17014949
TI  - The effects of time delays in a phosphorylation-dephosphorylation pathway.
AB  - Complex signaling cascades involve many interlocked positive and negative
      feedback loops which have inherent delays. Modeling these complex cascades often
      requires a large number of variables and parameters. Delay differential equation
      models have been helpful in describing inherent time lags and also in reducing
      the number of governing equations. However the consequences of model reduction
      via delay differential equations have not been fully explored. In this paper we
      systematically examine the effect of delays in a complex network of
      phosphorylation-dephosphorylation cycles (described by Gonze and Goldbeter, J.
      Theor. Biol., 210, (2001) 167-186), which commonly occur in many biochemical
      pathways. By introducing delays in the positive and negative regulatory
      interactions, we show that a delay differential model can indeed reduce the
      number of cycles actually required to describe the phosphorylation
      dephosphorylation pathway. In addition, we find some of the unique properties of
      the network and a quantitative measure of the minimum number of delay variables
      required to model the network. These results can be extended for modeling complex
      signalling cascades.

PMID- 17014950
TI  - Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI) for the
      treatment of stress urinary incontinence: a systematic review.
AB  - OBJECTIVE: Surgery and pelvic floor muscle training are established methods for
      treating stress urinary incontinence (SUI). A new serotonin and noradrenaline
      reuptake inhibitor, duloxetine, has been studied in multiple phase 3 trials as a
      form of medical management of this condition. This systematic review determined
      the effectiveness and acceptability of duloxetine in managing SUI. METHODS: We
      reviewed all randomised controlled trials comparing duloxetine with placebo or no
      treatment. The search included the Cochrane Incontinence Group specialised
      register, CENTRAL, MEDLINE, PREMEDLINE, dissertation abstracts, and the reference
      lists of relevant articles. The primary outcome was the number of participants
      whose symptoms were "cured" while on treatment. Secondary outcomes included
      subjective improvement, incontinent episodes, quality of life, adverse events,
      and discontinuation rates. RESULTS: Nine trials were included, totalling 3063
      women with predominantly SUI, all randomised to receive duloxetine or placebo.
      Treatment duration was 3-36 wk. Subjective cure favoured duloxetine (from three
      trials, 10.8% vs. 7.7%; RR=1.42; 95%CI, 1.02-1.98, p=0.04). The limited data
      available to assess objective cure rates were consistent with this. Individual
      studies showed a significant reduction in the Incontinence Episode Frequency
      (IEF) by approximately 50% during treatment. Duloxetine groups had significantly
      better quality-of-life scores (weighted mean difference for Incontinence Quality
      of Life Index for participants on 80 mg daily: 4.5; 95%CI, 2.83-6.18; p<0.00001)
      and rates of symptom improvement. Adverse effects were common (71% vs. 59%) but
      are reported as not serious and were equivalent to about one in eight
      participants reporting adverse effects (most commonly nausea) directly related to
      duloxetine treatment. About one in eight stopped treatment as a consequence of
      taking duloxetine (17% vs. 4%). CONCLUSIONS: Duloxetine can significantly improve
      the quality of life of patients with SUI, but it is unclear whether or not
      benefits are sustainable. Side-effects such as nausea are common.

PMID- 17014951
TI  - Monte Carlo simulation of early molecular evolution in the RNA World.
AB  - The origin of life remains a highly speculative field, mainly due to the shortage
      of our knowledge on prebiotic chemistry and basic understanding on the essence of
      life. In this context, computer simulation is expected to play an important role.
      For instance, the scenario concerning the genesis of the widely accepted RNA
      World remains blurry, though we have gathered some circumstantial evidence and
      fragmented knowledge on several supposed stages, including formation of
      polynucleotides from a prebiotic nucleotide pool, emergence of RNA replicases
      (RNA molecules catalyzing their own replication), and evolution of RNA
      replicases. It is highly valuable to simulate the stages as a continuous process
      to evaluate the plausibility of the supposition and study the rules involved.
      Here we construct a computer simulation on the process using Monte Carlo method.
      It demonstrates that primordial RNA replicases may appear and spread in a
      nucleotide pool provided they could recognize their own sequence and their
      complements as catalytic targets, and then may evolve to more efficient RNA
      replicases. Apart from its indication on the genesis of the RNA World, the vivid
      simulation of emergence of the "first replicative molecules" and their subsequent
      evolution is impressive and may help to get insight into "how could self
      replication and Darwinian evolution, two key features of life, emerge in a non
      life background?" thus improve our understanding of "what is life" when studying
      origins of life.

PMID- 17014952
TI  - Self-organizing proto-replicators and the origin of life.
AB  - Standard theories suggest that the first informational replicator involved RNA
      molecules (or a more primitive analogue) and that a preliminary step for the
      development of such replicating systems may have been the emergence of subunits
      capable of forming chains and interchain pairings. Following these hypotheses,
      this discussion describes various abstract simulations designed to investigate
      the structures resulting from such interactions for generalised subunits. Three
      classes of pairing strategy were considered for a range of subunit
      concentrations. The resulting dynamic self-organization of the systems produced
      high levels of structural complexity (some at low subunit concentrations and in
      the presence of disruptive subunits) and a significantly increased percentage of
      complementary base pairing (particularly in the more substantial structures).
      These properties of the systems, which did not require pre-existing replicators,
      templates or functional catalysts, were shown to be sensitive to the form of
      pairing strategy, subunit concentrations and various conditions that could
      theoretically be altered by products of the systems. Though no systems behaved as
      a replicator, some possessed collections of properties from which a replicating
      system might theoretically be constructed without requiring the introduction of
      additional classes of properties. The implications of such systems were
      considered with respect to the origin of life.

PMID- 17014953
TI  - Reduction of COD in wastewater from an organized tannery industrial region by
      Electro-Fenton process.
AB  - Advanced oxidation processes (AOPs) have led the way in the treatment of aqueous
      waste and are rapidly becoming the chosen technology for many applications. In
      this paper, COD reduction potential of leather tanning industry wastewaters by
      Electro-Fenton (EF) oxidation, as one of the AOPs, was experimentally evaluated.
      The wastewater sample was taken from an outlet of an equalization basin in a
      common treatment plant of an organized tannery industrial region in Istanbul,
      Turkey. Treatment of the wastewater was carried out by an electrochemical batch
      reactor equipped with two iron electrodes, which were connected parallel to each
      other. The oxidation process was studied for optimization of H(2)O(2) and the
      electricity consumptions were observed at different contact times under different
      pH conditions (3.0, 5.0 and 7.2). In each case, electricity consumption for
      decreased COD mass was estimated. In this process, COD was reduced by 60-70%
      within 10 min. By taking into consideration the local sewerage discharge limit,
      applicability of EF process for the tannery wastewaters was evaluated.

PMID- 17014954
TI  - Differential effects of cardiac sympathetic afferent stimulation on neurons in
      the nucleus tractus solitarius.
AB  - Activation of the cardiac "sympathetic afferent" reflex (CSAR) has been reported
      to depress the arterial baroreflex and enhance the arterial chemoreflex via a
      central mechanism. In the present study, we used single-unit extracellular
      recording techniques to examine the effects of stimulation of cardiac sympathetic
      afferents on baro- or chemosensitive neurons in the nucleus tractus solitarius
      (NTS) in anesthetized rats. Of 54 barosensitive NTS neurons tested for their
      response to epicardial application of capsaicin (0.4 microg), 38 were
      significantly (P<0.01) inhibited by 38% while 16 did not respond. Of 42 NTS
      chemosensitive neurons tested for their response to capsaicin, 33 were
      significantly (P<0.01) excited by 47% while 9 did not respond. In addition, of 12
      both barosensitive and chemosensitive NTS neurons tested for capsaicin, 2 were
      excited, 7 were inhibited, and 3 did not respond. In conclusion, this study
      indicates that CSAR activation inhibited NTS barosensitive neurons and excited
      NTS chemosensitive neurons, suggesting that the NTS plays an important role in
      processing the interactions between these cardiovascular reflexes.

PMID- 17014955
TI  - Brain phospholipid and triglyceride fatty acid content and pattern in Type 1 and
      Type 2 diabetic rats.
AB  - The liver phospholipid and triglyceride content and/or fatty acid pattern
      differ(s) not solely in normal versus diabetic rats, but also in distinct rat
      models of diabetes mellitus. The present study reveals that a comparable
      situation prevails in the brain. Fed and overnight fasted female normal rats (N)
      and Goto-Kakizaki rats (GK), as well as fed rats rendered diabetic by a prior
      injection 3 days before sacrifice of streptozotocin (STZ) were examined. The
      brain phospholipid content, expressed as milligrams of fatty acids per gram wet
      weight, was comparable in all groups of rats, with an overall mean value of
      31.2+/-0.8 (n=22). The GK rats differed from N and STZ rats by lower
      C18:0/C18:1omega9 and C18:2omega6/C18:3omega6 ratios and a lower C20:5omega3
      content of brain phospholipids. The total amount of fatty acids in triglycerides
      was 7-8 times higher in GK than N and STZ rats. The GK rats differed from N and
      STZ rats by lower C16:0/C16:1omega7, C18:0/C18:1omega9 and
      (C16:0+C16:1omega7)/(C18:0+C18:1omega9) ratios in triglycerides. These findings
      extend to the brain, the knowledge of alterations in phospholipid and
      triglyceride content and/or fatty acid pattern in GK rats, as compared to N or
      STZ rats. The former rats indeed displayed: (i) an apparently increased activity
      of Delta9- and Delta6-desaturases, as suggested by the phospholipid measurements,
      and a decreased C20:5omega3 content in such phospholipids; (ii) a dramatic
      increase in brain triglyceride content; and (iii) an increased activity of Delta9
      desaturase, as well as elongase, as judged from the triglyceride data.

PMID- 17014956
TI  - Association of DSC1, a gene modulated by adrenergic stimulation, with Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a complex multifactorial disorder involving a number
      of genetic and environmental factors, with severe head injury consistently
      reported as a major non-genetic risk factor. The adrenergic activation that
      occurs during major trauma increases cAMP levels, therefore the cAMP signaling
      pathway might be involved in AD pathogenesis. Time course of candidate gene
      expression following adrenergic stimulation with isoproterenol was assayed in
      neuroblastoma cells by quantitative reverse transcription (RT)-PCR. Then, genetic
      association studies of polymorphisms in several of these candidate genes were
      performed. Association studies in two independent case-control samples showed a
      polymorphism in DSC1, encoding desmocollin 1--a member of the desmosomal
      cadherins--which modulated AD susceptibility in a gender-specific manner. These
      results are in accordance with the potential involvement of the adrenergic
      signaling pathway in AD pathogenesis.

PMID- 17014957
TI  - Alpha-MSH and gamma-MSH modulate early release of hypothalamic PGE2 and NO
      induced by IL-1beta differently.
AB  - Interleukin-1beta (IL-1beta) stimulates corticotropin-releasing hormone (CRH)
      secretion in hypothalamus, which involves the release of prostaglandins (PGE2)
      and nitric oxide (NO). We have demonstrated that melanocortins can inhibit the
      early effects of IL-1beta on the HPA axis by acting on the central nervous system
      (CNS). Our study investigated whether alpha-melanocyte stimulating hormone (alpha
      MSH) and gamma-MSH could inhibit IL-1beta-induced PGE2 and NO release in
      hypothalamus in the rapid activation of the HPA axis. An i.c.v. injection of 12.5
      ng/microl of IL-1beta significantly increased the release of PGE2 and NOS
      activity in the hypothalamus. Treatment with alpha-MSH (0.1 microg/microl)
      inhibited the effect of IL-1beta on PGE2 release. Also, gamma-MSH (1
      microg/microl) eliminated the increase in NOS activity induced by IL-1beta. Our
      data indicate the modulatory role of melanocortins in the early hypothalamic
      response to IL-1beta, with different regulation of PGE2 and NO release.

PMID- 17014958
TI  - Ptychodiscus brevis toxin-induced depression of spinal reflexes involves 5-HT via
      5-HT3 receptors modulated by NMDA receptor.
AB  - The involvement of 5-hydroxytryptaminergic (5-HT) system for the Ptychodiscus
      brevis toxin (PbTx)-induced depression of spinal reflexes was evaluated. The
      reflex potentials were recorded at ventral root by stimulating the corresponding
      dorsal root in neonatal rat spinal cord in vitro. Superfusion of PbTx (2.8
      84microM) depressed the monosynaptic (MSR) and polysynaptic (PSR) reflexes in a
      concentration-dependent manner. The depression of the reflexes was maximal with
      84microM of the toxin. Ondansetron (0.1microM), a 5-HT(3) receptor antagonist,
      blocked the PbTx-induced depression of MSR and PSR. Spiperone (a 5-HT(2A)
      antagonist) or ketanserin (5-HT(2A/2C) antagonist and also at 5-HT(1B/1D)) failed
      to block the PbTx-induced depression of the reflexes. The 5-HT concentration of
      the cords was increased by four-fold after exposure to PbTx (28microM) and the
      increase was not seen in the cords pretreated with dl-2 amino-5-phosphonovaleric
      acid (APV, a NMDA receptor antagonist). Superfusion of 5-HT or phenylbiguanide
      (PBG, a 5-HT(3) receptor agonist) also produced depression of the spinal reflexes
      in a concentration-dependent manner. The 5-HT-induced depression of reflexes was
      blocked by ondansetron but not by spiperone. The results demonstrate that the
      PbTx-induced depression of spinal reflexes involves 5-hydroxytryptamine via 5
      HT(3) receptors modulated by NMDA receptor.

PMID- 17014959
TI  - Expression of NGF and trkA mRNA in song control and other regions of the zebra
      finch brain.
AB  - We used in situ hybridization to measure the expression of NGF and trkA mRNA in
      the zebra finch brain at posthatch day 11 (P11), P25, and in adulthood.
      Expression of NGF and trkA was restricted to specific areas of the telencephalon
      in the adult zebra finch brain. Interestingly the expression of NGF and trkA
      overlapped in most brain regions, suggesting that NGF acts at sites close to
      cells that synthesize it. In song regions of adults, both NGF and trkA were
      clearly expressed in lMAN, HVC, and RA in males and in lMAN and RA in females. At
      P11, NGF and trkA mRNA were detected only in RA in both sexes. At P25, when sex
      differences in lMAN and RA begin to emerge, NGF mRNA was expressed in lMAN and RA
      in both sexes and trkA was detected at low levels in lMAN in both sexes. Whereas
      the level of trkA expression in RA of males at P25 was consistently low but
      detectable, expression in females was not detected. The volume of RA defined by
      NGF was significantly larger in males than females at P25. We also found a
      tendency for the intensity of NGF in RA to be higher in males than in females at
      P25, although the difference was not statistically significant. The presence of
      NGF and trkA mRNA in RA and lMAN at P25 suggests that they may participate in
      sexually dimorphic neural development of RA and lMAN, possibly by participating
      in sex-specific cell survival.

PMID- 17014960
TI  - Occurrence of complement protein C3 in dying pyramidal neurons in rat hippocampus
      after systemic administration of kainic acid.
AB  - To evaluate the roles of complement in kainic acid (KA)-induced neuronal damages,
      the immunohistochemical localization of the complement protein C3 was examined in
      rat hippocampus after systemic KA injection. The immunoreactivity for C3 was
      found in glial cells in control rats, and such glial cells were increased in
      number after KA injection. Our confocal study showed that C3-positive glial cells
      were microglia. Three to seven days after KA, C3 immunoreactivity appeared in CA1
      and CA3 pyramidal neurons. Double staining for C3 combined with the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labelling showed that
      occurrence of C3 immunoreactivity in neurons coincided well with that of DNA
      fragmentation. Western blot analysis and RT-PCR experiments suggested local
      synthesis of C3 by brain cells. Our results suggest that C3 contributes greatly
      to neuronal death after systemic KA administration, and that microglia and
      neurons are the local source of C3 in KA-induced brain injury.

PMID- 17014961
TI  - Image distortions in SEM and their influences on EBSD measurements.
AB  - The high sample tilt angle commonly necessary for an orientation determination by
      EBSD (electron back-scatter diffraction) is responsible for some simple
      geometrically caused, but nevertheless essential, image distortions. First of
      all, the influence of the tilt correction and also the trapezium distortion which
      appears at low magnifications will be discussed. In the second part, an
      additional rhomboidal distortion will be introduced which is independent of the
      magnification used. This distortion appears if the scanned sample surface is out
      of plane to the tilted stage. Even a small deviation from the parallelity
      produces an approximately three times bigger error of the Euler angle phi(1) when
      the sample alignment is based on the image captured from the highly tilted
      sample. This effect especially concerns small samples (e.g. FIB-lamellae) since
      they cannot be exactly aligned, but the measurements of bigger samples can also
      be influenced. As an example a correction procedure is described in detail, based
      on a repetition of the measurement after a 180 degrees sample rotation.

PMID- 17014963
TI  - Nitric-oxide synthase: a cytochrome P450 family foster child.
AB  - Nitric-oxide synthase (NOS), the enzyme responsible for mammalian NO generation,
      is no cytochrome P450, but there are striking similarities between both enzymes.
      First and foremost, both are heme-thiolate proteins, employing the same
      prosthetic group to perform similar chemistry. Moreover, they share the same
      redox partner, a diflavoprotein reductase, which in the case of NOS is
      incorporated with the oxygenase in one polypeptide chain. There are, however,
      also conspicuous differences, such as the presence in NOS of the additional
      cofactor tetrahydrobiopterin, which is applied as an auxiliary electron donor to
      prevent decay of the oxyferrous complex to ferric heme and superoxide. In this
      review similarities and differences between NOS and cytochrome P450 are analyzed
      in an attempt to explain why NOS requires BH4 and why NO synthesis is not
      catalyzed by a member of the cytochrome P450 family.

PMID- 17014962
TI  - Deletion of selenoprotein P upregulates urinary selenium excretion and depresses
      whole-body selenium content.
AB  - Deletion of the mouse selenoprotein P gene (Sepp1) lowers selenium concentrations
      in many tissues. We examined selenium homeostasis in Sepp1(-/-) and Sepp1(+/+)
      mice to assess the mechanism of this. The liver produces and exports
      selenoprotein P, which transports selenium to peripheral tissues, and urinary
      selenium metabolites, which regulate whole-body selenium. At intakes of selenium
      near the nutritional requirement, Sepp1(-/-) mice had whole-body selenium
      concentrations 72 to 75% of Sepp1(+/+) mice. Genotype did not affect dietary
      intake of selenium. Sepp1(-/-) mice excreted in their urine approximately 1.5
      times more selenium in relation to their whole-body selenium than did Sepp1(+/+)
      mice. In addition, Sepp1(-/-) mice gavaged with (75)SeO(2-)(3) excreted 1.7 to
      2.4 times as much of the (75)Se in the urine as did Sepp1(+/+) mice. These
      findings demonstrate that deletion of selenoprotein P raises urinary excretion of
      selenium. When urinary small-molecule (75)Se was injected intravenously into
      mice, over 90% of the (75)Se appeared in the urine within 24 h, regardless of
      selenium status. This shows that urinary selenium is dedicated to excretion and
      not to utilization by tissues. Our results indicate that deletion of
      selenoprotein P leads to increased urinary selenium excretion. We propose that
      the absence of selenoprotein P synthesis in the liver makes more selenium
      available for urinary metabolite synthesis, increasing loss of selenium from the
      organism and causing the decrease in whole-body selenium and some of the
      decreases observed in tissues of Sepp1(-/-) mice.

PMID- 17014964
TI  - FTIR studies of the redox partner interaction in cytochrome P450: the Pdx-P450cam
      couple.
AB  - Recently we have developed a new approach to study protein-protein interactions
      using Fourier transform infrared spectroscopy in combination with titration
      experiments and principal component analysis (FTIR-TPCA). In the present paper we
      review the FTIR-TPCA results obtained for the interaction between cytochrome P450
      and the redox partner protein in two P450 systems, the Pseudomonas putida P450cam
      (CYP101) with putidaredoxin (P450cam-Pdx), and the Bacillus megaterium P450BM-3
      (CYP102) heme domain with the FMN domain (P450BMP-FMND). Both P450 systems reveal
      similarities in the structural changes that occur upon redox partner complex
      formation. These involve an increase in beta-sheets and alpha-helix content, a
      decrease in the population of random coil/3(10)-helix structure, a redistribution
      of turn structures within the interacting proteins and changes in the protonation
      states or hydrogen-bonding of amino acid carboxylic side chains. We discuss in
      detail the P450cam-Pdx interaction in comparison with literature data and
      conclusions drawn from experiments obtained by other spectroscopic techniques.
      The results are also interpreted in the context of a 3D structural model of the
      Pdx-P450cam complex.

PMID- 17014965
TI  - FoxM1: at the crossroads of ageing and cancer.
AB  - Forkhead transcription factors are intimately involved in the regulation of
      organismal development, cell differentiation and proliferation. Here we review
      the current knowledge of the role played by FoxM1 in these various processes.
      This particular member of the Forkhead family is broadly expressed in actively
      dividing cells and is crucial for cell cycle-dependent gene expression in the G2
      phase of the cell cycle. FoxM1 plays a crucial role in insuring the fidelity of
      the cell division process, as inhibition of FoxM1 activity results in serious
      aberrancies during mitosis, such as frequent chromosome missegregation, defects
      in cytokinesis and overt aneuploidy. FoxM1 expression also appears to be tightly
      correlated with the proliferative rate of a cell. For example, FoxM1 is one of
      the most significantly down-regulated genes in prematurely aged human fibroblasts
      (Progeria syndrome), while elevated expression of FoxM1 is seen in most human
      carcinomas. These observations suggest that interference with FoxM1 activity may
      contribute to the increase in mitotic errors seen in human diseases such as
      cancer and early onset of ageing diseases. In this review, several aspects of
      FoxM1 function will be discussed, as well as their implication in tumorigenesis.

PMID- 17014966
TI  - Bilobalide prevents ischemia-induced edema formation in vitro and in vivo.
AB  - EGb761, a standardized extract of Ginkgo biloba, has neuroprotective properties
      in animal models of ischemia, an activity that is partially attributed to its
      constituent, bilobalide. EGb761 has also been reported to inhibit edema formation
      induced by toxins such as triethyltin. The goal of this study was to test the
      activity of pure bilobalide to prevent edema formation in models of ischemia.
      Oxygen-glucose deprivation (OGD) in rat hippocampal slices served as a model of
      in vitro-ischemia. OGD caused cellular edema formation as indicated by an
      increase of slice water contents in 30 min. Bilobalide (1-10 microM) reduced
      slice water contents in ischemic slices in a concentration-dependent manner. As a
      model of in vivo-ischemia, we performed middle cerebral artery occlusion (MCAO)
      in mice. Permanent MCAO caused cell death and swelling of the ischemic hemisphere
      within 24 h. Pretreatment of the mice with bilobalide (10 mg/kg i.p.) reduced
      infarct area by 43% (as judged by 2,3,5-triphenyl-tetrazolium chloride (TTC)
      staining) and edema formation by 70% (as judged by hemispheric enlargement). In
      parallel experiments, pretreatment with bilobalide also reduced forebrain water
      contents in the ischemic hemisphere by 57%. As an alternative model of brain
      edema formation, we used water intoxication to increase brain water content;
      bilobalide, was, however, inactive in this model. We conclude that bilobalide
      strongly and specifically attenuates edema formation in models of brain ischemia
      in vitro and in vivo. Bilobalide may be therapeutically effective in brain edema
      which occurs secondarily to large hemispheric stroke and traumatic brain injury
      in humans.

PMID- 17014967
TI  - An edible vaccine for malaria using transgenic tomatoes of varying sizes, shapes
      and colors to carry different antigens.
AB  - Malaria, a disease caused by protozoan parasites of genus Plasmodium, is one of
      the world's biggest scourges. Over two billion individuals reside in the malaria
      endemic areas and the disease affects 300-500 million people annually. As a
      result of malarial-infection, an estimated three million lives are lost annually,
      among them over one million children (majority under 5 years of age). The
      mortality due to malaria has increased because of the spread of drug-resistant
      strains of the parasite, the breakdown of health services in many affected areas,
      the interaction of the disease with human immunodeficiency virus (HIV) infection,
      and possibly the effects of climate change. Infants and young children with
      malaria often die from severe anemia, cerebral involvement,or prostration caused
      by overwhelming infection; many new borns die from complications of low birth
      weight caused by maternal malaria during pregnancy. The scarce economic resources
      and lack of communication, infrastructure and adequate means of travel in the
      endemic areas make it extremely difficult to implement traditional infection
      control measures (i.e., mosquito control, preventive anti-malarial drugs and
      nets). To make the matter worse, both malarial parasites and its insect vectors
      are increasingly becoming resistant to anti-malarial agents (chloroquine) and
      insecticides (both DDT and melathione and related chemicals), respectively. By
      conventional wisdom, the immune mechanisms responsible for protection against
      malaria will require a multiple of 10-15 antigen targets for proper protection
      against various stages of malarial infection. By standard vaccination protocols,
      such a large number of targets would not be appropriate to be used for
      vaccination as a single dose due to antigenic competition. It would be almost
      impossible to immunize over two billion individuals who live in malaria
      susceptible areas with several carefully crafted immunization schedules delivered
      4-6 weeks apart in the form of two different antigens as a single dose. Besides,
      if immunization schedules could be arranged, the stability of vaccines carrying
      different malarial antigens, their transport, and the logistics of vaccination
      would be an almost impossible task to achieve under the current fiscal
      constraints. We are proposing a unique way to circumvent these logistical
      difficulties to deliver the malaria vaccines to every susceptible home at a small
      fraction of a cost. We hypothesize that the anti-malaria edible vaccines in
      transgenic tomato plants where different transgenic plants expressing different
      antigenic type(s). Immunizing individuals against 2-3 antigens and against each
      stage of the life cycle of the multistage parasites would be an efficient,
      inexpensive and safe way of vaccination. Tomatoes with varying sizes, shapes and
      colors carrying different antigens would make the vaccines easily identifiable by
      lay individuals.

PMID- 17014968
TI  - Accurate magnetic resonance imaging of atherosclerotic plaques: change future
      strategies for the diagnosis and therapy of atherosclerotic disease.
AB  - In recent years, magnetic resonance imaging (MRI) have been developed to image
      atherosclerosis and is emerging as a useful tool to assess the burden of
      atherosclerosis, whereas the potential influence on the diagnosis and therapy of
      atherosclerotic disease have not been fully determined. MRI allows for three
      dimensional evaluation of vascular structures and outstanding depiction of
      various components of the atherosclerotic plaque. The self-contained
      intravascular MRI probe appears to hold promise in the identification of high
      risk coronary and peripheral atherosclerotic lesions. Molecular and targeted
      contrast MRI can offer exciting possibilities of direct visualization of biologic
      processes within atherosclerotic tissue. The addition of quantitative hydrogen 1
      magnetic resonance spectroscopy and diffusion weighted imaging within
      atherosclerotic plaques can provide important data on the biological activity of
      potentially vulnerable lesions. Therefore, we hypothesized that accurate magnetic
      resonance imaging of atherosclerotic plaques maybe further affect and change
      future strategies for the diagnosis and therapy of atherosclerotic disease.

PMID- 17014969
TI  - Differential effects of empty and filled intervals on duration estimation by
      pigeons: tests of an attention-sharing explanation.
AB  - Pigeons were trained in a within-subjects design to discriminate durations of an
      empty interval and a filled interval. Even when different stimuli were used to
      mark empty intervals and to signal filled intervals, pigeons judged empty
      intervals to be longer than equal-length filled intervals. This timing difference
      was not a result of pigeons timing marker duration on empty interval trials.
      Increasing marker duration did not produce an overestimation of the empty time
      intervals. It was suggested that this timing difference could be due to a
      reduction in attention to temporal processing on filled interval trials when
      visual stimuli are used. Consistent with this hypothesis, it was found that empty
      intervals were judged longer than filled intervals when testing occurred in a
      darkened test room, but not when the test room was illuminated. In addition, no
      timing difference was observed when different auditory stimuli were used as
      markers for empty intervals and as signals for filled intervals.

PMID- 17014970
TI  - Conservation and expression of a novel alternatively spliced Evi1 exon.
AB  - The Evi1 transcriptional repressor protein is expressed in a developmentally
      regulated manner, is essential for normal development, participates in regulating
      cell proliferation and differentiation of cells of haemopoietic and neuronal
      origin and contributes to the progression of leukaemia. In this report we
      describe a new murine Evi1 gene transcript (Delta105) that contains two
      alternatively spliced regions encoding a 9 amino acid insertion (Rp+9) within the
      repressor domain (Rp) and a 105 amino acid C-terminal truncation. Abundant levels
      of the 105 amino acid truncated protein are observed in murine leukaemia cells.
      The combined primary sequence alterations do not affect the DNA binding,
      transcriptional repressor or CtBP2 protein binding properties of Evi1 but they do
      reduce its transforming and cell proliferation stimulating activities. Reduced
      transforming activity is most likely due to the C-terminal truncation as the
      activity of Evi1 containing either Rp or Rp+9 is indistinguishable. Both isoforms
      exist in all murine tissues and cell lines examined. However, only the Rp+9
      alternative splice variant is also found in humans and other vertebrates. Murine
      and human forms of Evi1 with Rp or Rp+9 exist. The additional 9 amino acids are
      encoded by a conserved 27 nucleotide exon, the overall structural organisation of
      the gene being preserved in the two species. The function of the Rp+9 and
      Delta105 splice variants is unknown although the conservation of Rp+9 throughout
      evolution in vertebrate species suggests it is essential to the broad spectrum of
      biological activities attributed to this developmentally essential protein.

PMID- 17014971
TI  - Radical amino acid change versus positive selection in the evolution of viral
      envelope proteins.
AB  - To detect positive selection in protein-coding sequence evolution, the ratio of
      the nonsynonymous to synonymous substitution rate (K(A)/K(S)) is commonly used.
      When this ratio is higher than 1, positive selection on nonsynonymous changes is
      considered to have occurred. However, the question of what kinds of amino acid
      change are likely to be involved in positive selection has not been well studied,
      though intuitively it seems that radical changes frequently occur in positively
      selected changes. To address this question, we examined chemically radical and
      conservative replacements in the evolution of hepatitis C virus (HCV) protein
      sequences. In the envelope region, 34 positively and 440 negatively selected
      sites were identified by the K(A)/K(S) ratio. Radical and conservative changes
      were compared between the two types of selected sites using two methods. First,
      the numbers of radical and conservative replacements were counted at the
      positively and negatively selected sites according to three kinds of chemical
      classifications. In all three classifications, the resulting ratios of the two
      numbers were not statistically different for the two types of selected sites
      (P>0.05). Second, the distribution of chemical changes was compared between the
      two types of selected sites using two kinds of chemical distances. The
      distributions of the two chemical distances were not statistically different for
      the two types of selected sites (P>0.05). These results indicate that the ratio
      of chemically radical and conservative changes is similar for positively and
      negatively selected sites in the envelope protein of HCV or, in other words,
      there is no correlation between radical change and positive selection in the
      evolution of this protein.

PMID- 17014972
TI  - Computational prediction of RpoS and RpoD regulatory sites in Geobacter
      sulfurreducens using sequence and gene expression information.
AB  - RpoS, the sigma S subunit of RNA polymerase, is vital during the growth and
      survival of Geobacter sulfurreducens under conditions typically encountered in
      its native subsurface environments. We investigated the conservation of sites
      that may be important for RpoS function in G. sulfurreducens. We also employed
      sequence information and expression microarray data to predict G. sulfurreducens
      genome sites that may be related to RpoS regulation. Hierarchical clustering
      identified three clusters of significantly downregulated genes in the rpoS
      deletion mutant. The search for conserved overrepresented motifs in co-regulated
      operons identified likely -35 and -10 promoter elements upstream of a number of
      functionally important G. sulfurreducens operons that were downregulated in the
      rpoS deletion mutant. Putative -35/-10 promoter elements were also identified in
      the G. sulfurreducens genome using sequence similarity searches to matrices of 
      35/-10 promoter elements found in G. sulfurreducens and in Escherichia coli. Due
      to a sufficient degree of sequence similarity between -35/-10 promoter elements
      for RpoS, RpoD, and other sigma factors, both the sequence similarity searches
      and the search for conserved overrepresented motifs using microarray data may
      identify promoter elements for both RpoS and other sigma factors.

PMID- 17014973
TI  - Development and application of an indirect ELISA test for the detection of
      antibodies to Mycoplasma crocodyli infection in crocodiles (Crocodylus
      niloticus).
AB  - Non-availability of a standardized rapid serodiagnostic test for quick and
      accurate diagnosis of Mycoplasma crocodyli (M. crocodyli) infection in crocodiles
      was the underlining reason for conducting the present study. An indirect enzyme
      linked immunosorbent assay (iELISA) for the detection of antibodies (Ab) to M.
      crocodyli infection in crocodile sera was developed using sonicated antigen (Ag)
      and anti-crocodile conjugate. The iELISA test was optimised with different
      reagents and at different steps. A cut-off value of percent positive greater than
      or equal to 53.47% resulted in an estimated sensitivity and specificity of 85.67
      and 100%, respectively. The developed iELISA could be used for detection of Abs
      to M. crocodyli infection in crocodiles and may enable to understand the
      transmission of the disease.

PMID- 17014974
TI  - Post-testicular changes in the density and distribution of intramembrane
      particles of stallion sperm surface domains.
AB  - Freeze-fracture replicas of stallion spermatozoa, collected from the proximal
      caput, corpus and cauda epididymides regions, were analyzed by electron
      microscopy to explore the distribution and density of intramembrane particles
      (IMP). Conspicuous differences in density and arrangement of the IMP were
      observed in the different topographical domains of mature and immature
      spermatozoa. A reduction of IMP, especially remarkable in the post-acrosomal
      domain, was observed in mature epididymal spermatozoa when compared with samples
      collected from ductuli efferentes. Some structural species-specific differences
      were also observed. The significance of these changes has not been determined,
      but remodeling of membrane components during developmental processes constitutes
      a fine control mechanism to ensure that key molecules are in the correct membrane
      position and during an appropriate timeframe to mediate fertilization.

PMID- 17014975
TI  - Effect of breed and sperm concentration on the changes in structural, functional
      and motility parameters of ram-lamb spermatozoa during storage at 4 degrees C.
AB  - The objectives of this study were (1) to determine the changes in structural,
      functional and motility parameters of ram-lamb semen stored at two different
      concentrations at 4 degrees C for 8 days in egg-yolk based extender and (2) to
      determine the effect of breed of ram-lambs on the changes in structural,
      functional and motility parameters of ram-lamb semen from different breeds stored
      at two different concentrations at 4 degrees C for 8 days in egg-yolk based
      extender. Two different concentrations suitable for laparoscopic and cervical
      insemination were employed in this experiment. A total of 14 ram-lambs (Polled
      Dorset-5, Suffolk-5, Katahdin-4) with satisfactory breeding potential were
      selected. Semen samples were collected by electro-ejaculation. Semen samples were
      extended to 50 and 200 million sperm per ml with a commercial egg yolk based
      extender (Triladyl, Minitube of America, Verona, WI, USA) at room temperature and
      were stored at 4 degrees C. The sperm DNA fragmentation index (DFI), percentages
      of high mitochondrial membrane potential (hMMP) and plasma membrane integrity
      (PMI) were assessed using flow cytometry as part of structural and functional
      parameters on Days 0, 1, 4, 6, and 8. A computer assisted sperm analyser (HTM
      IVOS, Version 10.8, Hamilton Thorne Research, Beverly, MA, USA) was used to
      assess the sperm motility parameters on Days 0, 1, 4, 6, and 8. PROC MIXED
      procedure was used to determine the effect of days of storage, concentration and
      breed. The concentration and days of storage significantly affected the sperm
      structural, functional and motility parameters (P<0.0001). Significant
      concentration x days of storage interaction was found for all structural and
      functional parameters. There was a significant concentration x days of storage
      interaction for average path velocity, curvilinear velocity, straightness and
      linearity. Overall changes in the sperm structural, functional and sperm motility
      parameters over the storage period were less dramatic in the 200 x 10(6) ml(-1)
      concentration when compared to 50 x 10(6) ml(-1) concentration. The hMMP and
      total progressive motility were influenced by breed. In conclusion, the quality
      of structural, functional and motility parameters declined as days of storage
      were increased and the magnitude of changes in the parameters was less dramatic
      at the higher concentration.

PMID- 17014976
TI  - PVP magnetic nanospheres: biocompatibility, in vitro and in vivo bleomycin
      release.
AB  - PURPOSE: To synthesize and characterize a magnetic micromolecular delivery system
      based on PVP hydrogel with polyvinyl alcohol (PVA) as the crosslinker. METHODS:
      The microparticles were successfully prepared using 25 kGy Co-60 gamma-ray
      irradiation and characterized. Biocompatibility, in vitro and in vivo drug
      release tests were carried out. RESULTS AND DISCUSSION: Bleomycin was
      quantitatively released with in slightly over 8 h (hours) from the nanospheres
      containing 1mg bleomycin while the time was longer for those containing 5 mg. On
      the other hand free bleomycin quantitatively passed through the dialysis baffle
      with in only 3.5 h. For both 5 and 1 mg of bound bleomycin, it took up to 2 h to
      reach peak concentration compared to 30 min for the free drug. CONCLUSION: The
      PVP hydrogel magnetic nanospheres exhibited passive drug release that could be
      exploited to enhance therapeutic efficacy. The present results indicate that PVP
      hydrogel based magnetic nanospheres have potential as drug carriers in magnetic
      guided chemotherapeutic drug delivery.

PMID- 17014977
TI  - Xanthine oxidase inhibitory activity of some Indian medical plants.
AB  - Xanthine oxidase inhibitory activity was assayed from six species belonging to
      different families traditionally used for the treatment of gout and related
      symptoms by indigenous people of India. The aqueous, methanol-water mixture and
      methanolic extract of these plants were used for the experiment. Of the 18
      extracts assayed, 14 extracts demonstrated xanthine oxidase inhibitory activity
      at 100 microg/ml, among which 10 extracts showed an inhibition greater than 50%
      and IC(50) values below 100 microg/ml. The methanolic extracts of Coccinia
      grandis, Datura metel, Strychnos nux-vomica and Vitex negundo showed more than
      50% inhibition, hence, they were screened for their in vivo hypouricaemic
      activity against potassium oxonate-induced hyperuricaemia in mice. Methanolic
      extracts of Coccinia grandis and Vitex negundo showed a significant decrease in
      the serum urate level (3.90+/-0.07 mg/dl, P<0.001) and (6.26+/-0.06 mg/dl,
      P<0.01), respectively, when compared to hyperuricaemic control (11.42+/-0.14
      mg/dl). This effect is almost similar to the serum urate level of allopurinol
      (3.89+/-0.07 mg/dl).

PMID- 17014978
TI  - Erdheim Chester disease: cerebral involvement in childhood.
AB  - Erdheim Chester disease (ECD) is an uncommon, non-Langerhans form of
      histiocytosis, characterized by long bone sclerosis. To date, only approximately
      some 100 cases have been reported. The diagnosis is based on its peculiar
      radiological and pathological features. ECD disease is rarely expected
      preoperatively. Although the ECD is an adult illness it can rarely be seen in the
      childhood period. We reported the case of a 10-year-old boy who presented
      headache, paraparesis and with diabetes inspidus for 6 years. As far as we know,
      the case presented here is the first published report of intracranial involvement
      and unilateral bone sclerosis with ECD in childhood.

PMID- 17014979
TI  - A purpose-based evaluation of information for patients: an approach to measuring
      effectiveness.
AB  - OBJECTIVE: To assess the feasibility, internal reliability, and validity, of an
      assessment tool, purpose-based information assessment (PIA), that we had
      developed to evaluate how effectively information provided to patients addresses
      their individual purposes for the information. The study also demonstrated
      potential novel insight gained by the PIA assessment. METHODS: One hundred and
      eighty-two patients and family members were provided with a booklet on early
      stage prostate cancer and its treatment options, in the context of a clinical
      trial comparing two booklets. Using the PIA, participants rated the importance (4
      point Likert scale) of each of six previously identified common purposes for such
      information: to organize their thoughts, to understand their situation, to decide
      on treatment, to plan their future, to provide emotional support to others, and
      to discuss issues. Participants then rated how much their booklet helped address
      each of their purposes (4-point Likert scale). Evaluations were returned by mail.
      This report assesses the PIA evaluation of one of the booklets. RESULTS: One
      hundred and fifty-six (86%) participants returned evaluations. Participants
      wanted information for a mean of 5.8 purposes (range 2-7); 72.5% rated the
      booklet at different levels of helpfulness across their purposes. The assessment
      showed internal reliability on three constructs tested, and convergent validity
      on 10 of 11 tested. PIA's individualized purpose-based approach revealed how an
      overall assessment could be misleading: overall, the booklet was more effective
      at helping readers decide than at helping them plan (64.7% versus 55.8%,
      respectively, rated the booklet as "helpful" or better). However, among readers
      who rated the two purposes as "very important", the booklet had a mean
      helpfulness rating of 1.95 for deciding compared to a mean of 2.02 for planning.
      The result suggests that the booklet was not better at helping people decide than
      at helping them plan, for the readers who most needed the help. CONCLUSION: The
      PIA seems reliable and valid and adequately sensitive. The individualized purpose
      based approach to assessing information appears to provide more specific feedback
      and more insights into its effectiveness than a single, global evaluation.
      PRACTICE IMPLICATIONS: Developers of information source or educational tools for
      patients can use an individualized purpose-based assessment, such as the PIA, to
      identify strengths and limitations of the tools more precisely than global
      assessments.

PMID- 17014980
TI  - VEGF system expression in different stages of estrous cycle in the corpus luteum
      of non-treated and superovulated water buffalo.
AB  - Water buffaloes are easily adaptable animals, whose raising and economical
      exploitation have been growing in the last three decades all over the world.
      Hyperstimulation of ovarian function in this species is a common technique aiming
      to improve reproductive performance. Superovulatory treatment affects corpus
      luteum (CL) function, which is highly correlated to angiogenic process. The aim
      of this study was therefore to assess the temporal protein and mRNA expression of
      VEGF and its receptors in the CL of non-treated and superovulated buffaloes. For
      that purpose blood samples and CL from 36 healthy (30 untreated, groups 1-5, and
      6 superovulated, group 6) non-pregnant buffaloes were collected and the samples
      were divided into 6 groups according to the age of CL. Plasma samples were
      submitted to RIA to measure progesterone concentration and CL were subjected to
      immunohistochemistry and real time PCR for VEGF (vascular endothelial growth
      factor), Flt-1 (fms-like tyrosine kinase receptor 1) and KDR (kinase insert
      domain containing region). The VEGF system protein and mRNA expression during CL
      life span of untreated animals showed a specific time-dependent profile, although
      protein did not always reflect mRNA concentrations. VEGF expression in luteal
      cells was high correlated to plasma progesterone levels. Superovulated CL showed
      a significant increase of the VEGF-system protein and a significant decrease of
      mRNA expression compared to untreated animals in the same stage of the oestrous
      cycle. We conclude that VEGF, Flt-1 and KDR protein and mRNA expression in
      buffalo CL is dependent of estrous cycle stage and superovulatory treatment is
      able to increase the translation rate of this system.

PMID- 17014981
TI  - Reliability and validity of a computerized neurocognitive test battery, CNS Vital
      Signs.
AB  - CNS Vital Signs (CNSVS) is a computerized neurocognitive test battery that was
      developed as a routine clinical screening instrument. It is comprised of seven
      tests: verbal and visual memory, finger tapping, symbol digit coding, the Stroop
      Test, a test of shifting attention and the continuous performance test. Because
      CNSVS is a battery of well-known neuropsychological tests, one should expect its
      psychometric properties to resemble those of the conventional tests upon which it
      is based. 1069 subjects age 7-90 participated in the normative database for
      CNSVS. Test-retest reliability (TRT) was evaluated in 99 Ss who took the battery
      on two separate occasions, separated, on the average, by 62 days; the results
      were comparable to those achieved by equivalent conventional and computerized
      tests. Concurrent validity studies in 180 subjects, normals and neuropsychiatric
      patients, indicate correlations that are comparable to the concurrent validity of
      similar tests. Discriminant validity is supported by studies of patients with
      mild cognitive impairment and dementia, post-concussion syndrome and severe
      traumatic brain injury, ADHD (treated and untreated) and depression (treated and
      untreated). The tests in CNSVS are also sensitive to malingerers and patients
      with conversion disorders. The psychometric characteristics of the tests in the
      CNSVS battery are very similar to the characteristics of the conventional
      neuropsychological tests upon which they are based. CNSVS is suitable for use as
      a screening instrument, or as a serial assessment measure. But it is not a
      substitute for formal neuropsychological testing, it is not diagnostic, and it
      will have only a limited role in the medical setting, absent the active
      participation of consulting neuropsychologists.

PMID- 17014982
TI  - A genetic library screen for signaling proteins that interact with phosphorylated
      T cell costimulatory receptors.
AB  - In the past decade, the fundamental importance and therapeutic potential of
      costimulatory signals for lymphocyte activation have spurred a large amount of
      work in immunology, infection, cancer, autoimmune diseases, etc. However, the
      mechanisms behind T cell costimulation remain unclear, partly due to the lack of
      suitable techniques. There is an urgent need for functional genomic research to
      develop comprehensive approaches to direct identification of protein-protein
      interactions that are dependent on the posttranslational modification of one
      component of the complex, particularly in the field of T cell immunology. Using
      inducible costimulator (ICOS) as a model, we failed to find any proteins that
      associated with the cytoplasmic tail of ICOS by the yeast two-hybrid approach.
      Therefore, we have developed a new yeast three-hybrid system that facilitates the
      rapid screening of cDNA libraries to find signaling molecules that interact with
      phosphorylated T cell costimulatory receptors. We demonstrate the utility of this
      technique to detect the interaction between ICOS and the p85 regulatory subunit
      of phosphatidylinositol 3-kinase (PI3K). The p85 unit of PI3K is the only
      signaling molecule identified so far that interacts with ICOS. This system may be
      of great help in dissecting the mechanisms of T cell costimulation and could be
      applied to other receptors.

PMID- 17014983
TI  - Syntenic arrangements of the surface polysaccharide biosynthesis genes in
      Rhizobium leguminosarum.
AB  - We applied a genomic approach in the identification of genes required for the
      biosynthesis of different polysaccharides in Rhizobium leguminosarum bv. trifolii
      TA1 (RtTA1). Pulsed-field gel electrophoresis analyses of undigested genomic DNA
      revealed that the RtTA1 genome is partitioned into a chromosome and four large
      plasmids. The combination of sequencing of RtTA1 library BAC clones and PCR
      amplification of polysaccharide genes from the RtTA1 genome led to the
      identification of five large regions and clusters, as well as many separate
      potential polysaccharide biosynthesis genes dispersed in the genome. We observed
      an apparent abundance of genes possibly linked to lipopolysaccharide
      biosynthesis. All RtTA1 polysaccharide biosynthesis regions showed a high degree
      of conserved synteny between R. leguminosarum bv. viciae and/or Rhizobium etli. A
      majority of the genes displaying a conserved order also showed high sequence
      identity levels.

PMID- 17014984
TI  - Reverse transcription real-time PCR assays for detection and quantification of
      Borna disease virus in diseased hosts.
AB  - Borna disease is a severe, immunopathological disorder of the central nervous
      system caused by the infection with the Borna disease virus (BDV). The detection
      of BDV in diseased animals, mainly sheep and horses, is achieved by histological,
      immunohistochemical and serological approaches and/or PCR-based technologies. In
      the present study, reverse transcription, real-time PCR assays were established
      for the detection of BDV in the brain tissue from sheep and horses, using loci
      for the p40 (nucleoprotein) and the p24 (phosphoprotein) genes. The PCRs were
      equally specific and sensitive, detecting 10 target molecules per reaction and
      one BDV-infected cell among 10(6) non-infected cells. In tissues from BDV
      diseased sheep and horses, the p24 target was detected at higher abundance than
      for p40. Therefore, the p24 test is suggested to be of higher value in the
      diagnostic laboratory. However, both assays should be useful for addressing
      questions in pathogenesis and for detecting BDV reservoirs in endemic areas.

PMID- 17014985
TI  - Voice parameters in children with Down syndrome.
AB  - Down syndrome (DS) is the most frequent chromosomal disorder. Commonly,
      individuals with DS have difficulties with speech and show an unusual quality in
      the voice. Their phenotypic characteristics include general hypotonia and
      maxillary hypoplasia with relative macroglossia, and these contribute to
      particular acoustic alterations. Subjective perceptual and acoustic assessments
      of the voice (Praat-4.1 software) were performed in 66 children with DS, 36 boys
      and 30 girls, aged 3 to 8 years. These data were compared with those of an age
      matched group of children from the general population. Perceptual evaluations
      showed significant differences in the group of children with DS. The voice of
      children with DS presented a lower fundamental frequency (F(0)) with elevated
      dispersion. The conjunction of frequencies for formants (F(1) and F(2)) revealed
      a decreased distinction between the vowels, reflecting the loss of articulatory
      processing. The DS vocalic anatomical functional ratio represents the main
      distinctive parameter between the two groups studied, and it may be useful in
      conducting assessments.

PMID- 17014986
TI  - Acoustic analysis of consonants in whispered speech.
AB  - An acoustic analysis of whispered consonants in comparison to normally phonated
      consonants was conducted in time and intensity domains. Consonant duration and
      average root mean square intensity were measured for six speakers in both
      articulation modes. Each of 25 Serbian consonants (C) was sited between the vowel
      /a/ forming a syllable of /aCa/ type. Such a syllable was placed in initial,
      medial, and final position in the carrier sentence. Results showed that whispered
      consonants have a prolonged duration of about 10% on average (statistically
      significant, ANOVA test), and that the unvoiced consonants have a smaller time
      dimension extension (5.8%) than voiced ones (15.3%). Examination at subphonemic
      level showed that there is no difference in voice-onset-time and affrication
      duration in unvoiced plosives and affricates, in both whispered and phonated mode
      of articulation, but the difference is significant for voiced ones. Analysis of
      consonant duration versus place of articulation showed that palatal place is most
      sensitive in the process of whispering. In all experiments, the results are very
      consistent with respect to the subjects and test material (Pearson's correlation
      was between 0.6 and 0.9). In intensity domain, all unvoiced consonants in
      whispered mode of articulation have almost unchanged intensity in comparison to
      phonated mode (the difference is maximum 3.5 dB). On the contrary, voiced
      consonants in the whispered mode were reduced in intensity by as much as 25 dB,
      as nasals and semivowels. Average intensity of whispered consonants is lowered by
      12d B in comparison to phonated ones, and does not depend on syllabic position
      inside the sentences.

PMID- 17014987
TI  - Vocal improvement after voice therapy in unilateral vocal fold paralysis.
AB  - Unilateral vocal fold paralysis (UVFP) is associated with changes in acoustic and
      aerodynamic voice measurements and can have a significant impact on a patient's
      quality of life. Few objective data regarding the efficacy of voice therapy for
      UVFP exist. The aim of this study was to retrospectively analyze voice
      modifications in a group of patients with UVFP before and after voice therapy.
      Forty patients with UVFP of different etiology were included in the study. Each
      subject had voice therapy with an experienced speech/language pathologist twice a
      week; the mean number of sessions was 12.6. A multidimensional assessment
      protocol was used; it included videoendoscopy, the maximum phonation time (MPT),
      the GIRBAS scale, spectrograms and a perturbation analysis, and the Voice
      Handicap Index (VHI). Pre- and posttreatment data were compared by means of the
      Wilcoxon and Student's t tests. A complete glottal closure was seen in 8 patients
      before voice therapy and in 14 afterward. Mean MPT increased significantly. In
      the perceptual assessment, the difference was significant for five out of six
      parameters. A significant improvement was found on spectrographic analysis; as
      for perturbation analysis, the differences in jitter, shimmer, and noise-to
      harmonic ratio values were significant. VHI values showed a clear and significant
      improvement. A significant improvement of voice quality and quality of life after
      voice therapy is an often reached and reasonable goal in patients with UVFP.

PMID- 17014988
TI  - Mucosal wave: a normophonic study across visualization techniques.
AB  - Visualization of vocal fold vibration is essential for accurate diagnoses and
      optimal treatment of persons with voice disorders. Recently, scientific and
      anecdotal reports have evidenced an increased amount of variation in the
      diagnostically relevant features of extent and symmetry of mucosal wave magnitude
      in normophonic speakers. The objectives of this study were to preliminarily
      ascertain the variation in mucosal wave magnitude and symmetry for normophonic
      speakers as assessed via standard and novel techniques, and compare findings
      across modal and pressed phonations. A correlational design with a multiple
      baseline across visualization methods approach was used. Mucosal wave presence,
      magnitude, and symmetry from 52 normophonic speakers were judged via stroboscopy,
      high-speed videoendoscopy (HSV) playback, mucosal wave playback, and mucosal wave
      kymography playback. Results demonstrate a prevalence of atypical magnitude and
      symmetry of mucosal wave during modal and pressed phonations by normophonic
      persons, differences across techniques, and a relationship between judgments and
      habitual fundamental frequency. Given the prevalence of mucosal wave magnitude
      and symmetry variations in the normophonic population, overdiagnosis may be
      possible without caution. The various visualization techniques provided unique
      information suggesting that it may be beneficial to use both full view and
      kymographic visualization techniques in combination. A major restriction of the
      current commercial HSV systems is the frame rate, typically limited to 2000
      frames per second, which appears insufficient for most female habitual
      phonations.

PMID- 17014989
TI  - A theoretical network model to analyse neurogenesis and synaptogenesis in the
      dentate gyrus.
AB  - We describe a strongly biologically motivated artificial neural network approach
      to model neurogenesis and synaptic turnover as it naturally occurs for example in
      the hippocampal dentate gyrus (DG) of the developing and adult mammalian and
      human brain. The results suggest that cell proliferation (CP) has not only a
      functional meaning for computational tasks and learning but is also relevant for
      maintaining homeostatic stability of the neural activity. Moderate rates of CP
      buffer disturbances in input activity more effectively than networks without or
      very high CP. Up to a critical mark an increase of CP enhances synaptogenesis
      which might be beneficial for learning. However, higher rates of CP are rather
      ineffective as they destabilize the network: high CP rates and a disturbing input
      activity effect a reduced cell survival. By these results the simulation model
      sheds light on the recurrent interdependence of structure and function in
      biological neural networks especially in hippocampal circuits and the interacting
      morphogenetic effects of neurogenesis and synaptogenesis.

PMID- 17014990
TI  - V4 receptive field dynamics as predicted by a systems-level model of visual
      attention using feedback from the frontal eye field.
AB  - Visual attention is generally considered to facilitate the processing of the
      attended stimulus. Its mechanisms, however, are still under debate. We have
      developed a systems-level model of visual attention which predicts that attentive
      effects emerge by the interactions between different brain areas. Recent
      physiological studies have provided evidence that attention also alters the
      receptive field structure. For example, V4 receptive fields typically shrink and
      shift towards the saccade target around saccade onset. We show that receptive
      field dynamics are inherently predicted by the mechanism of feedback in our
      model. According to the model an oculomotor feedback signal from an area involved
      in the competition for the saccade target location, e.g. the frontal eye field,
      enhances the gain of V4 cells. V4 receptive field dynamics can be observed after
      pooling the gain modulated responses to obtain a certain degree of spatial
      invariance. The time course of the receptive field dynamics in the model resemble
      those obtained from macaque V4.

PMID- 17014991
TI  - Recurrent multinodular neurilemmoma of the female upper lip.
AB  - Neurilemmoma is the most commonly encountered nerve sheath tumour of the oral
      cavity. It generally appears as a single encapsulated nodule. The tongue is
      involved most frequently and the lip rarely. The tumour is usually uninodular.
      Multinodular neurilemmoma of the upper lip is very rare and has been reported in
      only one patient. This is the first reported case of multinodular neurilemmoma in
      the upper lip of a female.

PMID- 17014992
TI  - Osteopontin and bone metabolism in healing cranial defects in rabbits.
AB  - Non-collagen proteins such as bone sialoprotein and osteopontin (OPN) form 10% of
      the extracellular bone matrix. In this study, the influence of OPN on bone repair
      was investigated. Human OPN (Innogenetics) was produced by a recombinant
      technique and bonded onto the surface of hydroxyapatite (Interpore 200). Thirty
      rabbits were divided into six equal groups. A circular defect (10mm) was prepared
      in each parietal bone. In four rabbits of each group the left and right defects
      were filled with either OPN-coated hydroxyapatite (OPN-HA) or non-coated
      hydroxyapatite (HA). One sham animal of each group received no implants. The
      animals were killed after 1, 2, 6, 12, 18 and 30 weeks. The histological sections
      were scanned and analysed digitally. There were no statistically significant
      differences in total bone formation between defects filled with OPN-HA and HA.
      Bone formation at the borders of the healing area was significantly higher in
      defects filled with OPN-HA than in those filled with HA. Less bone formation was
      noted in the OPN-HA and HA groups at the centre of the healing area than at the
      borders of the healing area and the dural area. Although some animals in the sham
      group showed a high level of bone formation in the dural area, this was not
      significantly different to that in the dural area of the other groups. There was
      no sign of infection or tissue rejection of the graft.

PMID- 17014993
TI  - Trans-sinusoidal maxillary distraction in three cleft patients.
AB  - The trans-sinusoidal maxillary distractor (TS-MD) was used to achieve maxillary
      advancement in three patients with repaired cleft lip and palate. After
      preoperative computer-aided planning of the distraction vectors, each TS-MD was
      bent on a stereolithographic model of the maxilla of the patient. The devices
      were intraoperatively positioned using a methyl-methacrylate template. After
      standard Le Fort I osteotomy the devices were intraorally activated. After
      distraction the devices remained in situ for 3 months as rigid internal fixation
      of the maxilla. All patients were successfully distracted according to protocol.
      Maxillary advancement was 12, 8 and 11 mm. In two patients, additional maxillary
      widening of 6 and 8 mm was achieved by choosing divergent distraction vectors.
      After distraction a clockwise rotation of the maxilla was observed in two
      patients. There was no relapse during the 3 months of consolidation and 12-month
      follow-up. The TS-MD allows not only distraction but also rigid internal fixation
      after distraction. It was easy to apply but difficult to remove. Owing to
      preoperative 3D planning of the distraction vectors, the results were
      predictable, but clockwise rotation of the maxilla during distraction should be
      considered in planning. The distractor did not interfere with function or social
      activities during distraction and retention periods. After removal it left no
      extraoral scars.

PMID- 17014994
TI  - Intraoperative local anaesthesia for paediatric postoperative oral surgery pain-
      a randomized controlled trial.
AB  - The aim of this study was to improve the pain experience for children following
      oral surgery under general anaesthesia. To this end, the efficacy and safety of
      intraoperative local anaesthetic (2% lidocaine with 1:200,000 epinephrine) for
      postoperative pain control was investigated. In a randomized controlled trial,
      142 patients aged 12 years or less, who were scheduled for dental extractions
      under general anaesthesia, received local anaesthesia or saline intraoral
      injection after induction of anaesthesia. There was statistically no significant
      difference between groups for pain scores recorded preoperatively, on waking, at
      30 min, at 24h, or for distress scores recorded preoperatively, on waking and at
      30 min. 'Severe' pain scores were recorded for 13% of treatment and 12% of
      control patients and 'very severe' for 13% of treatment and 10% of control
      patients on waking. These rates were similar at 30 min but reduced at 24h.
      Lip/cheek biting injuries occurred in one control and three treatment patients.
      Intraoperative local anaesthesia has been found to be effective for pain control
      following a range of other surgical procedures, but we did not find it to be
      effective in reducing postoperative pain or distress in children after oral
      surgery. Reasons may include unfamiliarity with altered orofacial sensation.

PMID- 17014995
TI  - Genetic and environmental influences on sensory gating of mid-latency auditory
      evoked responses: a twin study.
AB  - A deficit in sensory gating measured by the suppression of P50 auditory event
      related potential (ERP) has been implicated in the biological bases of
      schizophrenia and some other psychiatric disorders and proposed as a candidate
      endophenotype for genetic studies. More recently, it has been shown that gating
      deficits in schizophrenics extend to ERP components reflecting early attentive
      processing (the N1/P2 complex). However, evidence for heritability of sensory
      gating in the general population is very limited. Heritability of P50, N1, and P2
      amplitudes and gating was estimated in 54 monozygotic and 55 dizygotic twin pairs
      using a dual-click auditory paradigm. Genetic model-fitting analysis showed high
      heritability of peak amplitudes of P50, N1, and P2 waves. Genetic influences on
      P50 gating (S2/S1) were modest, while heritability of N1 and P2 gating was high
      and significant. The alternative gating measure (S1-S2 difference) showed
      significant heritability for all three ERP components. Weak genetic influences on
      P50 gating ratio can be related to its poor test-retest reliability demonstrated
      in previous studies. These results suggest that gating measures derived from the
      N1/P2 wave complex may be useful endophenotypes for population-based genetic
      studies of the sensory gating function and its impairments in psychopathology.

PMID- 17014996
TI  - Analysis of RNA recovery and gene expression in the epidermis using non-invasive
      tape stripping.
AB  - BACKGROUND: The recovery of RNA from the upper epidermis by tape stripping yields
      variable RNA mass but has not been evaluated for its dependence on anatomical
      location. Gene expression at different body locations and the origin of RNA
      recovered by tape stripping have not been investigated. OBJECTIVES: To
      characterize the recovery of RNA from different anatomical locations by tape
      stripping; to correlate the recovery of RNA and removal of barrier by tape
      stripping, as assayed by transepidermal water loss; and to investigate gene
      expression in the upper epidermis at different body locations. METHODS: Twelve
      subjects were tape stripped at 15 body locations. RNA mass was evaluated and gene
      expression assayed. Subjects were tape stripped 4, 8 and 12 times on the upper
      back and transepidermal water loss and RNA recovery assayed. RESULTS: Ranked by
      median RNA recovery, the following order was observed:
      mastoid>forehead>chest>upper back>mid back>cheek>lower
      back>deltoid>forearm>abdomen>ventral thigh>inner arm>shin>dorsal thigh>lower leg.
      Expression of the housekeeping gene mRNAs is found to be uniform and reproducible
      while IL-8 and TNFalpha mRNAs are expressed in different quantities both at
      different body sites within an individual and between individuals at a specific
      anatomical site. Data show a significant and high correlation between the number
      of tapes used to strip a site and transepidermal water loss but no strong
      correlation between transepidermal water loss and RNA recovery or number of tapes
      used to strip a site and RNA recovery. CONCLUSIONS: Subjects and anatomical
      location are shown to be significantly different for the ability to recover RNA
      by tape stripping. We hypothesize that RNA recovered by tape strip is not derived
      from corneocytes but from cells associated with the stratum corneum.

PMID- 17014997
TI  - Pulsed current iontophoresis of hyaluronic acid in living rat skin.

PMID- 17014998
TI  - Mechanistic model of acute autoinhibitory feedback action after administration of
      SSRIs in rats: application to escitalopram-induced effects on brain serotonin
      levels.
AB  - This study presents the development and evaluation of a feedback turnover model
      that mimics drug-induced effects on brain extracellular levels of serotonin (5
      HT) after acute administration of the selective serotonin reuptake inhibitor
      (SSRI) escitalopram (S-citalopram) in rats. The extracellular 5-HT output in the
      hippocampus was continuously monitored by intracerebral microdialysis in
      conjunction with serial arterial blood sampling for evaluation of escitalopram
      pharmacokinetics. 5-HT levels were significantly increased following
      administration of 2.5, 5 and 10 mg/kg of escitalopram and the 5-HT levels
      gradually declined to its baseline value within 360 min. However, at 5 and 10
      mg/kg, the response-time curves were almost identical. This might be explained by
      activation of serotonergic autoreceptors exerting negative feedback, leading to a
      reduced release of new 5-HT into the synapse. The dynamics of escitalopram-evoked
      changes of 5-HT response was characterized by a turnover model, which included an
      inhibitory feedback moderator component. Thus, the response acted linearly on the
      production of the moderator, which acted inversely on the production of response.
      The plasma kinetics served as input to an inhibitory function acting on the loss
      of response. Simultaneous fitting of the model after three constant rate
      infusions demonstrated the flexibility of the system. The efficacy (I(max)) and
      potency (IC(50)) of inhibition of reuptake were 0.9+/-0.03 and 4.4+/-1.4 ng/ml,
      respectively, corresponding to an EC(50) of escitalopram about 30 ng/ml. In
      conclusion, the model lends itself to 'what-if' predictions at different drug
      exposure scenarios, and has potential for extrapolation of the pharmacodynamics
      of SSRIs in man.

PMID- 17015000
TI  - Homothallism in Sclerotinia minor.
AB  - Sclerotinia species are sexually reproducing ascomycetes. In the past S. minor
      and S. sclerotiorum, have been assumed to be homothallic because of the self
      fertility of colonies derived from single ascospores. S. trifoliorum has
      previously been shown to be bipolar heterothallic due to the presence of four
      self-fertile and four self-sterile ascospores within a single ascus [Uhm, J.Y.,
      Fujii, H., 1983a. Ascospore dimorphism in Sclerotinia trifoliorum and cultural
      characters of strains from different-sized spores. Phytopathology73: 565-569].
      However, isolates of S. minor and S. sclerotiorum were proven to be homothallic
      ascomycetes, by self-fertility of all eight ascospores within an ascus. Apothecia
      were raised from all eight ascospores of a single tetrad from four isolates of S.
      minor and from an isolate of S. sclerotiorum, indicating that inbreeding may be
      the predominant breeding mechanism of S. minor. Ascospores from asci of S. minor
      and S. sclerotiorum were predominantly monomorphic, but rare examples of
      ascospore dimorphism similar to S. trifoliorum were found.

PMID- 17014999
TI  - Intranasal absorption of Delta(9)-tetrahydrocannabinol and WIN55,212-2 mesylate
      in rats.
AB  - The aim of this study was to examine the potential of the nasal route for
      systemic delivery of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and WIN55,212-2
      mesylate. Anesthetized rats were surgically prepared to isolate the nasal cavity,
      into which Delta(9)-THC (10 mg/kg) or WIN55,212-2 (150 microg/kg) in propylene
      glycol alone or propylene glycol and ethanol (9:1) were administered. Rats were
      also administered Delta(9)-THC (1 mg/kg) and WIN55,212-2 (150 microg/kg)
      intravenously in order to determine absolute bioavailabilities of the nasal
      doses. Plasma Delta(9)-THC and WIN55,212-2 concentrations were determined by
      liquid chromatography/mass spectroscopy (LC/MS). The pharmacokinetics of the
      drugs after intranasal administration was best described by a one-compartment
      model with an absorption phase. WIN55,212-2 was absorbed more rapidly (T(max)=0.2
      0.3h) than Delta(9)-THC (T(max)=1.5-1.6h) and to a higher extent than Delta(9)
      THC. Addition of ethanol (10%) to the formulations had no significant effect on
      the C(max) after nasal administration (p>0.05). Furthermore, it had no
      significant effect on the absolute bioavailability (F(abs)): F(abs)=6.4+/-2.4%
      and 9.1+/-3.0% for Delta(9)-THC in propylene glycol, with and without ethanol,
      respectively. For WIN55,212-2, F(abs)=49.9+/-6.9% (propylene glycol alone) and
      56.6+/-14.1% (propylene glycol with 10% ethanol). The results of the study showed
      that systemic delivery of Delta(9)-tetrahydrocannabinol and WIN55,212-2 could be
      achieved following nasal administration in rats.

PMID- 17015001
TI  - Two families of extracellular phospholipase C genes are present in aspergilli.
AB  - Fungi secrete extracellular enzymes to enable them to harvest nutrients from the
      environment. In the case of pathogenic fungi these enzymes can also be
      pathogenesis factors. Here we report the identification in fungi of a complex
      family of extracellular phospholipase C (PLC) enzymes, homologous to the
      Pseudomonas aeruginosa PLCH_PSEAE. Database searches and phylogenetic analysis
      showed that the PLCs clustered into two groups with different evolutionary
      histories. One group, subdivided into PLC-A, -B, -C and -D, was found only in
      aspergilli and Neosartorya fischeri. Each species only ever showed three of the
      four PLCs except N. fischeri which had all four PLCs plus duplicate PLC-A, -B and
      -C genes. Modelling studies indicated that these PLCs had mechanistic
      similarities to phosphoesterases and aryl sulphatases, but that they probably did
      not differ in substrate specificity. The second group, PLC-E, was seen in a wider
      range of fungi including some species of aspergilli and was always found in a
      head-to-head arrangement with a copper oxidase, similar to the laccases. The PLC
      genes appear to have arisen from separate gene transfer events from bacteria or
      lower eukaryotes. Thus, aspergilli have acquired PLCs twice in the course of
      evolution.

PMID- 17015002
TI  - Transformation of pulmonary histoplasmosis to sarcoidosis: a case report.
AB  - Histoplasmosis, a dimorphic fungus, and sarcoidosis, a disease of unknown
      etiology, share many clinical features, including typical manifestations of
      granulomatous inflammation involving the lungs and mediastinal lymphatics in
      association with constitutional symptoms. As such, they are often difficult to
      distinguish based upon clinical presentation. Recent studies suggest that
      sarcoidosis may be triggered by infectious agents. Here we present a case of
      documented pulmonary histoplasmosis that evolved into sarcoidosis. This case
      supports the notion that infections promote sarcoidosis in predisposed hosts.

PMID- 17015003
TI  - The clinical significance of interleukin 18 assessment in sarcoidosis patients.
AB  - INTRODUCTION: Sarcoidosis is a multisystemic disease of unknown etiology
      characterized by the formation of immune granulomas in involved organs. The
      cytokine profile in inflamed lesions of sarcoidosis is mainly determined by T
      helper 1 (Th1) cells. Interleukin 18 (IL-18) is primarily a monocyte/macrophage
      derived cytokine. IL-18 has been recently identified as an IFNgamma-inducing
      factor. The cytokine plays an important role in the induction of Th1 response and
      it may be responsible for sarcoidosis progression. The aim of the study was to
      assess the usefulness of IL-18 estimation in the sarcoidosis diagnosis and the
      disease course prognosis. MATERIAL AND METHODS: The diagnosis of sarcoidosis was
      established in 88 patients (the mean age of 38.1+/-10.8 years). We measured IL-18
      level in plasma and bronchoalveolar lavage fluid (BALF) cell culture supernatant
      (CCS) using the enzyme-linked immunoassay technique (ELISA). We also performed
      the flow cytometric analysis of BALF lymphocyte phenotype. Statistica 5.0 and non
      parametric tests: the Mann-Whitney U-test and the Spearman correlation test, were
      used for statistical analysis. RESULTS: The patient group consisted of 55
      subjects without acute symptoms of sarcoidosis, 14 patients with acute Lofgren
      syndrome and 19 subjects with Lofgren syndrome in the past. Lung hilar
      lymphadenopathy was diagnosed in 49 patients and lung interstitial changes in 39
      subjects. After 6-month-observation, 49 patients were in remission, 20 subjects
      manifested persistent disease and 19 patients had sarcoidosis progression. Plasma
      IL-18 level was significantly (P<0.0001) higher in sarcoidosis patients (383+/
      250pg/ml) than in control subjects (146+/-72pg/ml). Plasma IL-18 level was
      similar both in subjects with Lofgren syndrome and in other patients. However, IL
      18 level in BALF CCS was significantly (P<0.05) lower in Lofgren syndrome
      patients than in subjects without acute manifestation of the disease. The highest
      IL-18 level in plasma was found in patients with disease progression, in subjects
      with lung interstitial changes and in patients with extrapulmonary manifestation
      of the disease. We observed a positive correlation between plasma IL-18 level and
      the percentage of BALF lymphocytes (R=0.202, P=0.06) as well as the percentage of
      activated HLA DR+T cells (R=0.23, P<0.05). There was a negative correlation
      between the IL-18 level in BALF CCS and the percentage of BALF CD3-positive and
      CD4-positive lymphocytes (R=-0.27, -0.23, P<0.05). CONCLUSION: IL-18 may play a
      significant role in the prolongation of sarcoidosis course. Its estimation may
      become a good prognostic factor, which should be analyzed together with other
      factors useful in sarcoidosis monitoring.

PMID- 17015004
TI  - Endobronchial ultrasonography with distance for peripheral pulmonary lesions.
AB  - BACKGROUND: We assessed the effectiveness of applying the distance from the
      orifice of the bronchus to visualized peripheral pulmonary lesion (PPL) under
      endobronchial ultrasonography (EBUS) to transbronchial biopsy (TBB), as an
      alternative to EBUS with a guide sheath (GS) and fluoroscopy. PATIENTS AND
      METHODS: From October 2004 to July 2005, a total of 158 consecutive patients with
      solitary PPLs, which were not visualized under flexible video bronchoscopy, were
      received EBUS for advanced localization subsequently. One hundred and thirteen of
      158 patients with solitary PPLs which were visualized on EBUS image were included
      in this prospective study and randomly divided into two groups for TBB using
      different methods. In group EBUS-D (57 patients) the distance from the bronchial
      orifice to pulmonary lesion was measured, then the biopsy forceps were advanced
      to this measured distance and biopsy followed. In group EBUS (56 patients) the
      biopsy forceps were advanced regardless of distance. The diagnostic yields were
      then compared. RESULTS: TBBs in group EBUS-D patients had a significantly higher
      diagnostic yield (45/57, 78.9%) than group EBUS patients (32/56, 57.1%)
      [P=0.013]. Size and location of lesion, duration of EBUS, diagnosis of
      malignancy, and whether the probe was located within the lesion on EBUS image did
      not differ between these two groups. Mild bleeding occurred in three patients in
      group EBUS-D and two in group EBUS. One group EBUS patient had a self-limited
      pneumothorax. CONCLUSIONS: Measuring and applying the distance between the
      orifice of bronchus and the lesion could increase the diagnostic yield of EBUS
      guided TBBs for PPLs.

PMID- 17015005
TI  - Pilot-scale experiment on anaerobic bioreactor landfills in China.
AB  - Developing countries have begun to investigate bioreactor landfills for municipal
      solid waste management. This paper describes the impacts of leachate
      recirculation and recirculation loadings on waste stabilization, landfill gas
      (LFG) generation and leachate characteristics. Four simulated anaerobic columns,
      R1-R4, were each filled with about 30 tons of waste and recirculated weekly with
      1.6, 0.8 and 0.2m(3) leachate and 0.1m(3) tap water. The results indicated that
      the chemical oxygen demand (COD) half-time of leachate from R1 was about 180
      days, which was 8-14 weeks shorter than that of R2-R4. A large amount of LFG was
      first produced in R1, and its generation rate was positively correlated to the
      COD or volatile fatty acid concentrations of influent leachates after the 30th
      week. By the 50th week of recirculation, the waste in R1 was more stabilized,
      with 931.2 kg COD or 175.6 kg total organic carbon released and with the highest
      landfill gas production. However, this contributed mainly to washout by leachate,
      which also resulted in the reduction of LFG generation potential and accumulation
      of ammonia and/or phosphorus in the early stage. Therefore, the regimes of
      leachate recirculation should be adjusted to the phases of waste stabilization to
      enhance efficiency of energy recovery. Integrated with the strategy of in situ
      leachate management, extra pre-treatment or post-treatment methods to remove the
      nutrients are recommended.

PMID- 17015006
TI  - Accelerated carbonation of municipal solid waste incineration fly ashes.
AB  - As a result of the EU Landfill Directive, the disposal of municipal solid waste
      incineration (MSWI) fly ash is restricted to only a few landfill sites in the UK.
      Alternative options for the management of fly ash, such as sintering,
      vitrification or stabilization/solidification, are either costly or not fully
      developed. In this paper an accelerated carbonation step is investigated for use
      with fly ash. The carbonation reaction involving fly ash was found to be optimum
      at a water/solid ratio of 0.3 under ambient temperature conditions. The study of
      ash mineralogy showed the disappearance of lime/portlandite/calcium chloride
      hydroxide and the formation of calcite as carbonation proceeded. The leaching
      properties of carbonated ash were examined. Release of soluble salts, such as
      SO4, Cl, was reduced after carbonation, but is still higher than the landfill
      acceptance limits for hazardous waste. It was also found that carbonation had a
      significant influence on lead leachability. The lead release from carbonated ash,
      with the exception of one of the fly ashes studied, was reduced by 2-3 orders of
      magnitude.

PMID- 17015007
TI  - Leachate injection using vertical wells in bioreactor landfills.
AB  - Leachate recirculation or liquid injection in municipal solid waste landfills
      offers economic and environmental benefits. The key objective of this study was
      to carry out numerical evaluation of key design variables for leachate
      recirculation system consisting of vertical wells. In order to achieve the
      objective, numerical modeling was carried out using the finite-element model
      HYDRUS-2D. The following design parameters were evaluated by simulating liquid
      pressure head on the liner and the wetted width of the waste under steady-state
      flow conditions: (1) hydraulic conductivities of the waste and vertical well
      backfill; (2) liquid injection rate and dosing frequency; (3) well diameter,
      screen height and screen depth; and (4) hydraulic conductivity of the leachate
      collection system, slope of the leachate collection system and spacing of the
      leachate collection pipes. The key findings of this study are as follows. The
      well diameter, hydraulic conductivity of the well drainage pack, and screen
      height and screen depth of the well have very little effect on the wetted width
      for a given liquid flux. The wetted width and the injection pressure for a given
      liquid flux decrease with the increase in the hydraulic conductivity of the
      waste. The pressure head on the liner increases with the decrease in the vertical
      distance between the bottom of the well screen and the top of leachate collection
      system. The liquid injection flux increases with the decrease in hydraulic
      conductivity of the leachate collection system. Unlike sand (k approximately 10(
      4)m/s), pea gravel (k approximately 0.01 m/s) resulted in less than 0.3m pressure
      head on the liner for all simulations carried out in this study.

PMID- 17015008
TI  - Self-assembled monolayers of polythiophene conductive polymers improve
      biocompatibility and electrical impedance of neural electrodes.
AB  - There is continued interest in the development of conductive polymer coatings to
      improve the electrical properties and biocompatibility of electrodes for neural
      prostheses. We present here a new type of coating, based on mixed self-assembled
      monolayers (SAMs) of thiolated poly(alkylthiophene)s and functionalized
      alkanethiols. When assembled as a SAM on electrodes designed for in vitro
      electrophysiology, these polymers are able to significantly lower electrode
      impedance at 1 kHz. The same mixed formulation is able to promote the outgrowth
      of neurites from primary mouse cortical neurons when the alkanethiol component is
      functionalized with a neural cell adhesion molecule (NCAM) binding antibody.
      Atomic force microscopy of the SAMs shows that they exert their effect through
      the well-known mechanism of increasing electrode surface area. These new
      covalently bound films have the potential to be more robust and are more
      controllable in their composition than existing electrodeposited conductive
      polymer coatings.

PMID- 17015009
TI  - Novel fluorescent sensing system for alpha-fructosyl amino acids based on
      engineered fructosyl amino acid binding protein.
AB  - A novel fluorescent sensing system for alpha-glycated amino acids was created
      based on fructosyl amino acid binding protein (FABP) from Agrobacterium
      tumefaciens. The protein was found to bind specifically to the alpha-glycated
      amino acids fructosyl glutamine (Fru-Gln) and fructosyl valine (Fru-Val) while
      not binding to epsilon-fructosyl lysine. An Ile166Cys mutant of FABP was created
      by genetic engineering and modified with the environmentally sensitive
      fluorophore acrylodan. The acrylodan-conjugated mutant FABP showed eight-fold
      greater sensitivity to Fru-Val than the unconjugated protein and could detect
      concentrations as low as 17 nM, making it over 100-fold more sensitive than
      enzyme-based detection systems. Its high sensitivity and specificity for alpha
      substituted fructosyl amino acids makes the new sensing system ideally suited for
      the measurement of hemoglobin A1c (HbA1c), a major marker of diabetes.

PMID- 17015010
TI  - Electrochemical recognition of anions by 1,1'-N,N'-ferrocenoylbisamino acid
      esters.
AB  - A series of novel ferrocene-based receptors, 1,1'-N,N'-ferrocenoylbisamino acid
      methyl esters 2-5 have been prepared and their electrochemical properties
      determined. The amino acids employed were glycine (2), beta-alanine (3), gamma
      aminobutyric acid (4) and l-norleucine (5). These receptors are composed of an
      electroactive core and two parallel strands of amino acids that can interact with
      anions via electrostatic interactions in the oxidized state as well as secondary
      interactions, such as hydrogen bonding and hydrophobic interactions. Furthermore,
      the semi-rigid molecular clefts between the two strands of amino acids in these
      receptors are capable of discerning anions of different geometries and sizes. The
      anion sensing capabilities of receptors 2-5 were studied using cyclic voltammetry
      (CV). The anions studied were chloride (Cl-), nitrate (NO3-), dihydrogen
      phosphate (H(2)PO(4)-), hydrogen sulfate (HSO(4)-), acetate (CH(3)COO-) and
      neurologically important anions such as lactate (CH(3)CH(OH)COO-), pyruvate
      (CH(3)COCOO-) and glutamate (HOOC-CH(NH2)CH(2)CH(2)COO-). The receptors 2-5
      exhibit selectivity towards chloride, dihydrogen phosphate and acetate, over
      hydrogen sulfate and nitrate ions and generate a redox response in organic media.
      Also, binding studies of receptor 3 with neurologically important anions show it
      displays selectivity towards lactate and pyruvate, over glutamate ions and
      generates a redox response. However the response is ill defined in all cases,
      with poorly separated "free" and "ion-pair" peaks, which preclude accurate
      measurement of the response by CV. These results emphasize the considerations
      required for the design of ferrocene-based receptors and the necessary parameters
      for efficient electrochemical recognition of small anions by CV.

PMID- 17015011
TI  - The protein-nanomaterial interface.
AB  - Developments in the past few years have illustrated the potentially
      revolutionizing impact of nanomaterials, especially in biomedical imaging, drug
      delivery, biosensing and the design of functional nanocomposites. Methods to
      effectively interface proteins with nanomaterials for realizing these
      applications continue to evolve. Proteins are being used to control both the
      synthesis and assembly of nanomaterials. There has also been an increasing
      interest in understanding the influence of nanomaterials on the structure and
      function of proteins. Understanding and controlling the protein-nanomaterial
      interface will be crucial for designing functional protein-nanomaterial
      conjugates and assemblies.

PMID- 17015012
TI  - Soluble guanylate cyclase.
AB  - Soluble guanylate cyclase (sGC) is a mammalian nitric oxide (NO) sensor. When NO
      binds to the sGC heme, its GTP cyclase activity markedly increases, thus
      generating cyclic GMP, which serves to regulate several cell signaling functions.
      A good deal is known about the kinetics and equilibrium of binding of NO to sGC,
      leading to a proposed multistep mechanism of sGC activation that involves at
      least two NO-binding sites. The crystal structure of a member of a recently
      discovered family of prokaryotic sGC homologues has provided important insights
      into structure-function relationships within the sGC family of proteins.

PMID- 17015013
TI  - Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic
      colorectal cancer.
AB  - Colorectal cancer (CRC) patients have increased levels of human neutrophil
      peptides 1-3 (HNP1-3) in tumour tissue and plasma. The aim is to study whether
      the amount of HNP1-3 in tumour and plasma from CRC patients correlate with Dukes'
      stages A-D. The amount of HNP1-3 in tumour tissue, normal colonic mucosa, and
      plasma was determined with mass spectrometry. Plasma levels of HNP1-3 were
      determined with enzyme-linked immuno-sorbent assay (ELISA). The amount of HNP1-3
      determined with mass spectrometry was increased in tumours compared to normal
      colonic tissue in CRC patients in Dukes' stage A-D, whereas HNP1-3 in plasma was
      only elevated in Dukes' stage D compared to healthy individuals. HNP1-3 plasma
      concentration determined with ELISA was increased in Dukes' stages C and D, but
      not in A and B. It is concluded that HNP1-3 is a potential marker for prognostic
      assessment, surveillance of patients, and monitoring chemotherapy in CRC patients
      with advanced disease.

PMID- 17015014
TI  - Generalisability of survival estimates for patients with breast cancer--a
      comparison across two population-based series.
AB  - The purpose of the study was to analyse the generalisability and geographic
      transportability of survival estimates produced by commonly used prognostic
      factors. We compared the influence of tumour size, histologic grade, axillary
      nodal status, oestrogen and progesterone receptor contents, age at diagnosis and
      two prognostication schemes (the Nottingham Prognostic Index and St. Gallen
      criteria) in two nationwide cohorts of patients diagnosed with breast cancer in
      1991-2, the FinProg (n=2923, Finland) and the SEER series (n=43,249, the United
      States (US)). Eight-year estimates of breast cancer-specific (84% versus 80%),
      relative (86% versus 83%), and overall (70% versus 69%) survival were slightly
      more favourable in the SEER than in the FinProg series, respectively. Despite
      differences in demographic variables and the frequency of use of adjuvant
      therapies and mammography screening between the series, the prognostic factors
      examined produced close to overlapping survival curves with similar shapes. The
      results suggest that quantitative survival estimates based on frequently used
      prognostic factors and prognostication schemes are generalisable and
      transportable between large, unselected cohorts of breast cancer patients.

PMID- 17015015
TI  - Charles Dickens: the man, medicine, and movement disorders.
AB  - Nineteenth-century Victorian novelists played an important role in developing our
      understanding of medicine and illness. With the eye of an expert clinician,
      Charles Dickens provided several detailed accounts of movement disorders in his
      literary works, many of which predated medical descriptions. His gift for
      eloquence, imagery, and precision attest not only to the importance of careful
      clinical observation, but also provide an insightful and entertaining perspective
      on movement disorders for modern students of neuroscience.

PMID- 17015016
TI  - A new model for translational regulation of specific mRNAs.
AB  - Recently, RNA helicase A (RHA) has been shown to facilitate translation of
      specific mRNAs by recognizing and binding to a complex structure at their 5' end
      known as the post-transcriptional control element. This implicates RHA, a member
      of the DEXD/H-box protein superfamily, in linking transcription and translation
      of a specific class of retroviral and cellular mRNAs. This exciting finding
      suggests a new mechanism for the regulation of the translation of specific
      transcripts.

PMID- 17015017
TI  - Atomic force microscopy: determination of unbinding force, off rate and energy
      barrier for protein-ligand interaction.
AB  - Recently, atomic force microscopy (AFM) based force measurements have been
      applied biophysically and clinically to the field of molecular recognition as
      well as to the evaluation of dynamic parameters for various interactions between
      proteins and ligands in their native environment. The aim of this review is to
      describe the use of the AFM to measure the forces that control biological
      interaction, focusing especially on protein-ligand and protein-protein
      interaction modes. We first considered the measurements of specific and non
      specific unbinding forces which together control protein-ligand interactions. As
      such, we will look at the theoretical background of AFM force measurement curves
      for evaluating the unbinding forces of protein-ligand complexes. Three AFM model
      dynamic parameters developed recently for use in protein-ligand interactions are
      reviewed: (i) unbinding forces, (ii) off rates, and (iii) binding energies. By
      reviewing the several techniques developed for measuring forces between
      biological structures and intermolecular forces in the literature, we show that
      use of an AFM for these applications provides an excellent tool in terms of
      spatial resolution and lateral resolution, especially for protein-protein and
      protein-ligand interactions.

PMID- 17015018
TI  - Formation of leptofibrils is associated with remodelling of muscle cells and
      myofibrillogenesis in the border zone of myocardial infarction.
AB  - Leptofibrils, or leptomeres, remain the least studied cytoskeletal structures in
      muscle cells, and their function and mechanism of assembly are still poorly
      understood. Our ultrastructural study of the surviving cardiac myocytes located
      in the perinecrotic border zone of the infarcted left ventricle in rats revealed
      intense formation of leptofibrils and leptofibrillar clusters during 4-15 days
      following experimental myocardial infarction. In the perinecrotic myocytes,
      leptofibrils developed predominantly in the subsarcolemmal areas, near
      disassembled intercalated discs and at the sites of intense myofibrillogenesis in
      the peripheral zones of the sarcoplasm. We found that the development of these
      structures occurred before or at the time of assembly of myofibrils. In our
      material, leptofibrils consisted of longitudinally oriented filamentous bundles
      inserted in electron dense Z-band-like material and periodically crossed by 3-8
      bands of this material with the period of cross-striation of 120-210 nm. The
      presence of leptofibrils in growing cytoplasmic processes and ruffles developing
      in the border zone in the areas of lost intercellular contacts indicates their
      formation de novo during post-infarction period. We observed four major
      morphological types of localization of these structures: (1) direct contact of
      one end of leptofibrils with Z bands of nascent, mature or disassembling
      myofibrils; (2) direct contact with the sarcolemma: (a) multifocal attachment of
      leptofibrils to the sarcolemma through the lateral surfaces of their minute Z
      band-like structures; (b) attachment of one or both ends of leptofibrils to the
      sarcolemma without contacts or in contact with myofibrils; (3) attachment of
      leptofibrils to subsarcolemmal accumulations of electron dense Z-band material in
      newly formed fasciae adherentes of the remodeled intercalated disks; (4)
      clustering and contacts of leptofibrils with one another predominantly at the
      level of their Z bands. Interestingly, most leptofibrils of all four types were
      topographically associated with the system of T-tubules, the sarcoplasmic
      reticulum and subsarcolemmal vesicles. Serial sections through the areas
      containing leptofibrils indicate their spindle-like or nearly cylindrical shape.
      Thus, we found that leptofibrils assemble in terminally differentiated cardiac
      myocytes following destabilization of their differentiated state and partial
      dedifferentiation induced by myocardial infarction. The results of this study
      demonstrate that formation of leptofibrils, earlier described mainly in the
      developing and malignant muscle, is temporally associated with adaptive
      structural remodelling and the activation of myofibrillogenesis in functionally
      overloaded cardiac myocytes of adult animals. Our findings suggest that re
      expression of some structural characteristics of the embryonic muscle appear to
      represent one of the mechanisms that underlie adaptive plasticity of the
      myocardium following injury and under conditions of hyperfunction.

PMID- 17015019
TI  - Excitation functions of (p,x) reactions on natural nickel between proton energies
      of 2.7 and 27.5 MeV.
AB  - Excitation functions have been measured for a number of proton induced nuclear
      reactions on natural nickel in the energy range from 27.5 MeV down to their
      threshold energy, using the activation method on stacked foils. Excitation
      functions for the reactions leading to the formation of (60)Cu, (61)Cu, (56)Ni,
      (57)Ni, (55)Co, (56)Co, (57)Co and (58)Co are presented and compared with earlier
      reported experimental data. Comparison with the recommended data reported by the
      International Atomic Energy Agency [Gul et al., 2001. Charged particle cross
      section database for medical radioisotope production. IAEA-TECDOC-1211, IAEA
      Vienna, Austria] is also presented when possible.

PMID- 17015020
TI  - Development and applications of the k0-based internal mono standard INAA method.
AB  - The k0-based internal monostandard instrumental neutron activation analysis (IM
      INAA) method, developed and standardized in our laboratory, is capable of
      analyzing both small and large samples of different sizes and shapes. Use of in
      situ relative efficiency makes the method geometry independent. In this paper, we
      present the development of this methodology and applications to two types of
      alloys namely, stainless steel and brass. A stainless steel certified reference
      material, BCS 466 was also analyzed to evaluate the accuracy of the method.
      Absolute concentrations in these alloys were arrived by a standard-less method.
      The method has also been applied for the analysis of large-size wheat samples
      (0.45-1 kg) and the results were compared with the data obtained for selected
      elements in sub-samples (50-1000 mg).

PMID- 17015021
TI  - Genomics and proteomics: emerging technologies in clinical cancer research.
AB  - Fueled by the complete genomic data acquired from the human genome project and
      the desperate clinical need of comprehensive analytical tools to study a
      heterogeneous disease like cancer, genomic and proteomic technologies have
      evolved rapidly, accelerating the rate and number of discoveries in clinical
      cancer research. These discoveries include mechanistic understanding of cancer
      biology as well as the identification of biomarkers supporting early detection,
      molecular classification of tumors, molecular predictors of metastasis, treatment
      response, and prognosis. While the technical advances have been significant,
      clinical researchers and practicing physicians are now confronted with the
      challenges of understanding technically and statistically complex data sets,
      translating this complex information to fit clinical contexts and incorporating
      it into clinical studies. In this review, we will summarize the available
      technologies and associated bioinformatics, discuss studies that are clinically
      relevant, and discuss the limitations we are still facing. We will present a
      framework for future directions of these technologies and how we believe they
      should be applied in clinical studies.

PMID- 17015022
TI  - New concepts in strongyle control and anthelmintic resistance: the role of
      refugia.

PMID- 17015023
TI  - Measurement of the femoral neck anteversion angle in the dog using computed
      tomography.
AB  - Simple and accurate limb and pelvic conformation evaluation using computed
      tomography (CT) can be useful in planning canine hip dysplasia (CHD) treatment
      and in helping to understand the pathogenesis of osteoarthritis and CHD. The
      objectives of this study were to describe a new method for femoral neck
      anteversion angle (FNA-angle) measurement in CT, and to compare it to the
      established radiographic standard biplanar method. The hips of 23 Estrela
      Mountain Dogs were evaluated using radiography and CT and their FNA-angles were
      determined by performing two CT examinations and with one radiographic
      measurement session. The intra-class correlation coefficient (ICC) was used to
      evaluate the repeatability (agreement between the two CT sessions, ICC=0.92) and
      reproducibility (agreement between each CT and radiographic session, ICC=0.91 in
      both cases) of the CT FNA-angle measurement method. This study suggests that CT
      FNA-angle measurement method is reliable and can be used in CT hip studies with
      confidence.

PMID- 17015024
TI  - A comparison of seroprevalence and risk factors for Theileria parva and T. mutans
      in smallholder dairy cattle in the Tanga and Iringa regions of Tanzania.
AB  - A cross sectional serological survey was carried out in two geographical small
      scale dairying areas of Tanzania to determine the distribution and prevalence and
      to quantify risk factors for Theileria parva and T. mutans during the period
      January to April 1999. The prevalence of serum antibodies to these two Theileria
      parasites was determined using an indirect enzyme-linked immunosorbent assay
      (ELISA) technique. The results suggest that the parasites are widely distributed
      through out the two study sites and seroprevalence of 23% and 48% for T. parva
      were obtained for Tanga and Iringa regions, respectively. Seroprevalence of T.
      mutans ranged from 17% in the Tanga region to 40% in the Iringa region. Farm and
      animal data were collected and analysed by multiple logistic regression models to
      explore the risk factors associated with seroprevalence to T. parva and T. mutans
      pathogens. In both regions, seroprevalence for the two Theileria spp. pathogens
      increased significantly with age. Pasture grazed animals were more likely to be
      seropositive than those that were zero-grazed. Among individual animal
      characteristics, seropositivity was higher in cash-bought and charity gifted
      animals compared to cattle obtained using a formal credit agreement. Further
      studies on the relative role of risk factors for theileriosis found in this study
      may assist in the development of an effective control package.

PMID- 17015025
TI  - Dutch translation of the fear of pain questionnaire: Factor structure,
      reliability and validity: a comment on.

PMID- 17015026
TI  - Pain and falls in older people.
AB  - Pain and falling both affect substantial segments of the older population.
      Despite the presence of several plausible mechanisms for pain to contribute to
      falling, very few studies have investigated this relationship in older people. If
      pain is a falls risk factor, this represents a potentially important point of
      intervention for falls prevention. Falls are a major cause of disability and loss
      of independent living status in older people. We examined the relationship
      between pain, pain-related interference with activities and falls in a cross
      sectional analysis of 3509 people aged 49 years or more in two postal code areas
      in New South Wales, Australia (the Blue Mountains Eye Study). We found that
      subjects reporting pain with moderate to severe level of pain-related
      interference with activities were more likely to report any falls or multiple
      falls in the past 12 months than subjects not reporting pain (adjusted prevalence
      ratios 1.42, p=0.0001 and 1.62, p=0.0156, respectively). We also found a
      significant trend in the association indicating an increasing likelihood of self
      reported falls associated with increasing level of pain-related interference with
      activities. The association was stronger for multiple falls than for any falls.
      Excluding subjects with recent fractures did not alter the findings. Given the
      high prevalence and public health importance of both conditions, further
      investigation of this association in prospective studies is recommended.

PMID- 17015027
TI  - Nicotine activates cell-signaling pathways through muscle-type and neuronal
      nicotinic acetylcholine receptors in non-small cell lung cancer cells.
AB  - Nicotinic acetylcholine receptors (nAChR) are expressed on non-neuronal cell
      types, including normal bronchial epithelial cells, and nicotine has been
      reported to cause Akt activation in cultured normal airway cells. This study
      documents mRNA and protein expression of subunits known to form a muscle-type
      nAChR in non-small cell lung cancer (NSCLC) cell lines. In one NSCLC examined,
      mRNA and protein for a heteropentamer neuronal-type alpha3beta2 nAChR was
      detected in addition to a muscle-type receptor. Protein for the alpha5 nAChR was
      also detected in NSCLC cells. Although, mRNA for the alpha7 nAChR subunit was
      observed in all cell lines, alpha7 protein was not detectable by immunoblot in
      NSCLC cell extracts. Immunohistochemistry (IHC) of NSCLC primary tissues from 18
      patients demonstrated protein expression of nAChR alpha1 and beta1 subunits, but
      not alpha7 subunit, in lung tumors, indicating preferential expression of the
      muscle-type receptor. In addition, the beta1 subunit showed significantly
      increased expression in lung tumors as compared to non-tumor bronchial tissue.
      The alpha1 subunit also showed evidence of high expression in lung tumors.
      Nicotine at a concentration of 10 microM caused phosphorylation of mitogen
      activated protein kinase (MAPK) (p44/42) that could be inhibited using nAChR
      antagonists. Inhibition was observed at 100 nM alpha-bungarotoxin (alpha-BTX) or
      10 microM hexamethonium (HEX); maximal inhibition was achieved using a
      combination of alpha-BTX and HEX. Akt was also phosphorylated in NSCLC cells
      after exposure to nicotine; this effect was inhibited by the PI3K inhibitor
      LY294002 and antagonists to the neuronal-type nAChR, but not to the muscle-type
      receptor. Nicotine triggered influx of calcium in the 273T NSCLC cell line,
      suggesting that L-type calcium channels were activated. 273T cells also showed
      greater activation of p44/42 MAPK than of Akt in response to nicotine. Cultures
      treated with nicotine and the EGFR tyrosine kinase inhibitor gefitinib showed a
      significant increase in the number of surviving cells compared to gefitinib
      alone. These data indicate that the muscle-type nAChR, rather than the alpha7
      type, is highly expressed in NSCLC and leads to downstream activation of the
      p44/42 MAPK pathway. Neuronal-type receptors are also present and functional, as
      evidenced by antagonist studies, although, the expression levels are lower than
      muscle-type nAChR. They also lead to downstream activation of MAPK and Akt.
      Nicotine may play a role in regulating survival of NSCLC cells and endogenous
      acetylcholine released locally in the lung and/or chronic nicotine exposure might
      play a role in NSCLC development. In addition, exposure of NSCLC patients to
      nicotine through use of nicotine replacement products or use of tobacco products
      may alter the efficacy of therapy with EGFR inhibitors.

PMID- 17015028
TI  - Neural representation of language: activation versus long-range connectivity.
AB  - Cognitive functions are thought to build on connectivity within large-scale
      neuronal networks, rather than on strictly localized processes. Yet, present
      understanding of neural mechanisms of language function, as derived from
      neuroimaging, is based on mapping brain areas that are more active during
      specific linguistic tasks than in control conditions. Connectivity can then be
      evaluated among those areas. However, network nodes should ideally be determined
      based on their correlated time series of activity. Recent developments in
      analysis methods now facilitate localization and characterization of functionally
      connected neural networks directly from real-time magnetoencephalography data.
      Analysis of long-range connectivity might clarify and expand the view provided by
      traditional neurophysiological and hemodynamic activation studies. Here, we use
      silent reading as the example process.

PMID- 17015029
TI  - Do deaf individuals see better?
AB  - The possibility that, following early auditory deprivation, the remaining senses
      such as vision are enhanced has been met with much excitement. However, deaf
      individuals exhibit both better and worse visual skills than hearing controls. We
      show that, when deafness is considered to the exclusion of other confounds,
      enhancements in visual cognition are noted. The changes are not, however,
      widespread but are selective, limited, as we propose, to those aspects of vision
      that are attentionally demanding and would normally benefit from auditory-visual
      convergence. The behavioral changes are accompanied by a reorganization of
      multisensory areas, ranging from higher-order cortex to early cortical areas,
      highlighting cross-modal interactions as a fundamental feature of brain
      organization and cognitive processing.

PMID- 17015030
TI  - Mechanisms underlying working memory for novel information.
AB  - In this Opinion article we describe a theory that the brain mechanisms underlying
      working memory for novel information include a buffer in parahippocampal
      cortices. Computational modeling indicates that mechanisms for maintaining novel
      information in working memory could differ from mechanisms for maintaining
      familiar information. Electrophysiological data suggest that the buffer for novel
      information depends on acetylcholine. Acetylcholine activates single-cell
      mechanisms that underlie persistent spiking of neurons in the absence of synaptic
      transmission, allowing maintenance of information without prior synaptic
      modification. fMRI studies and lesion studies suggest that parahippocampal
      regions mediate working memory for novel stimuli, and the effects of cholinergic
      blockade impair this function. These intrinsic mechanisms in parahippocampal
      cortices provide an important alternative to theories of working memory based on
      recurrent synaptic excitation.

PMID- 17015031
TI  - Molecular recognition at Langmuir monolayers.
AB  - In the field of chemical biology, molecular recognition has served as a basic
      concept to understand the construction of biological assemblies and the
      biological functions. Among the model systems available to investigate 'lock and
      key' interactions, the interfacial molecular recognition at the air-water
      interface is an appropriate system because it mimics one of the two coupled
      monolayers that can be viewed in a biological membrane. Amphiphilic derivatives
      bearing hydrophobic (C10-C26) and hydrophilic moieties can form a two-dimensional
      layer called a Langmuir monolayer. The binding of a non-surface active substance
      dissolved in the aqueous subphase underneath the Langmuir monolayer can be
      realized through the molecular recognition process.

PMID- 17015032
TI  - Reinterpreting pericentromeric heterochromatin.
AB  - In fission yeast, pericentromeric heterochromatin is directly responsible for the
      sister chromatid cohesion that assures accurate chromosome segregation. In
      plants, however, heterochromatin and chromosome segregation appear to be largely
      unrelated: chromosome transmission is impaired by mutations in cohesion but not
      by mutations that affect heterochromatin formation. We argue that the formation
      of pericentromeric heterochromatin is primarily a response to constraints on
      chromosome mechanics that disfavor the transmission of recombination events in
      pericentromeric regions. This effect allows pericentromeres to expand to enormous
      sizes by the accumulation of transposons and through large-scale insertions and
      inversions. Although sister chromatid cohesion is spatially limited to
      pericentromeric regions at mitosis and meiosis II, the cohesive domains appear to
      be defined independently of heterochromatin. The available data from plants
      suggest that sister chromatid cohesion is marked by histone phosphorylation and
      mediated by Aurora kinases.

PMID- 17015033
TI  - A new species of Acaenodera (Digenea: Acanthocolpidae) parasitizing Conger
      orbignyanus (Pisces: Congridae) from the coasts of Argentina.
AB  - A new species, Acaenodera spinosior, is described based on specimens collected
      from the intestine of Conger orbignyanus Valenciennes (Pisces: Congridae) caught
      in waters off Mar del Plata (38 degrees 08'S, 57 degrees 32'W), Argentina. Five
      of 36 congers examined were parasitized (prevalence: 13.9%, mean intensity: 2.6+/
      1.52, range: 1-5). The new species is distinguished from its only congener,
      Acaenodera placophora Manter and Pritchard, 1960, a parasite of congers off
      Hawaii, by its larger size, lacking eyespots, and exhibiting a greater number of
      circumoral, mid-ventral and lateral spines. This is the first record of
      Acaenodera Manter and Pritchard, 1960 in Atlantic waters.

PMID- 17015035
TI  - Co-constructing local meanings for child health indicators in community-based
      information systems: the UThukela District Child Survival Project in KwaZulu
      Natal.
AB  - In changing the context regarding the situation of vulnerable children in rural
      South Africa, understanding the role of communication in the design of community
      based child health information systems (HIS) is key. Communication goes beyond
      language. The importance of translation of terms and concepts used to negotiate
      between different meanings and logics is explored in this paper. In striving for
      the 'ideal speech situation' [J. Habermas, Structural Transformation of the
      Public Sphere, The MIT Press, Cambridge, MA, 1989], or, in other words, creating
      an enabling environment in which people can participate in debate and discussion
      on equal terms, there is a need to develop a codetermined vision; to understand
      local meanings of and for childhood illness; to understand communication systems
      and the context in which they occur; and to connect with networks beyond the
      localised setting, such as provincial or national health authorities. We provide
      a theoretical and practical framework in which important aspects of communication
      related to IS design can be highlighted and against which the implementation of
      an IS can be reviewed. The South African case study from the UThukela District
      Child Survival Project in KwaZulu-Natal, illustrates how this approach was used
      in co-constructing local meanings for child health indicators in a community
      based information system.

PMID- 17015034
TI  - Spectral investigations of preferential solvation and solute-solvent interactions
      of 1,4-dimethylamino anthraquinone in CH2Cl2/C2H5OH mixtures.
AB  - The optical absorption and IR spectra of 1,4-dimethylamino anthraquinone (1,4
      DMAAQ) in CH(2)Cl(2)/C(2)H(5)OH mixtures have been investigated. The preferential
      solvation of 1,4-DMAAQ in CH(2)Cl(2)/C(2)H(5)OH mixed solvents has been studied
      by monitoring the charge transfer band of 1,4-DMAAQ. The optical absorption
      spectral study indicates that 1,4-DMAAQ is preferentially solvated by CH(2)Cl(2)
      in CH(2)Cl(2)/C(2)H(5)OH mixtures. This can be confirmed by the observed index of
      preferential solvation value (delta(s1)) as well as higher mole fraction of
      CH(2)Cl(2) in the solvation microsphere (x(1)(L)) than in the bulk solvent
      (x(1)). The CH(2)Cl(2) molecules become more available to enter the solvation
      shell of 1,4-DMAAQ because of the hydrogen bonded clusters formed by ethanol
      molecules. This is also evident from the non-linear behavior of the transition
      energy (E(12)) as well as the absence of synergistic behavior. IR spectral
      studies show that the observed shifts in the nu(CO) and nu(NH) of 1,4-DMAAQ are
      due to the dipole-dipole interaction between the 1,4-DMAAQ and the associated
      ethanol.

PMID- 17015036
TI  - Hepatocyte transplantation: State of the art.
AB  - Advances in biotechnology have allowed hepatocyte transplantation as a relevant
      proposition to treat liver disease. This procedure may change the crescent
      mortality in liver transplantation waiting lists due global organ shortage.
      Recent clinical trials have described promising results of hepatocyte
      transplantation for acute, acute-on-chronic and metabolic liver disease. In this
      report, we discuss progresses regarding hepatocyte culture, cryopreservation
      systems, hepatocyte immortalization, suitable recipient site for hepatocyte
      engraftment, cell differentiation and fusion into hepatocytes, current clinical
      trials, and summarize the bioartificial liver systems. These progressions
      motivate expectation concerning hepatocyte transplantation as a consistent
      therapy for liver disease.

PMID- 17015037
TI  - Susceptibility to cholesterol gallstone formation: evidence that LITH genes also
      encode immune-related factors.
AB  - Cholesterol gallstones are solid calculi that form in the gallbladder from bile
      constituents and chiefly comprise cholesterol. Cholesterol gallstones are
      prevalent and costly for healthcare systems. In addition to various environmental
      factors, genetic risk contributes substantially to gallstone susceptibility.
      Candidate gene approaches to identify contributory genes are based on prior
      knowledge of gene-protein function. Whether selected from the entire genome or
      from limited genomic regions detected by experimental linkage analyses, thus far,
      candidate genes predominantly were related to lipid homeostasis. Alternatively,
      comprehensive review of available data suggests that a fundamental driving force
      underlying cholesterol gallstone formation is inflammation. Therefore, we predict
      that Lith genes in mice and LITH genes in humans also encode inflammatory
      molecules, their receptors and other mediators. Indeed, many Lith loci, defined
      experimentally using inbred mouse models, co-localise with genes that encode
      inflammation-related proteins. Systematic review of the literature reveals
      evidence consistent with inflammatory responses that may dictate each of the
      three cornerstones of cholesterol gallstone formation: biliary cholesterol
      supersaturation; cholesterol nucleation; gallbladder hypomotility. Genetically
      targeted inbred mice represent a powerful tool to interrogate the relationship
      between immune-related genes and gallstone susceptibility. We urge researchers to
      consider inflammation-related genes when designing population case-control
      genetic association studies pertaining to the genetic basis of gallstones. Immune
      and inflammatory events underlie each criterion necessary for cholesterol
      gallstone formation, which suggests that variation within the respective genes is
      fundamental for gallstone formation. In turn, inflammatory mediators may exert a
      spectrum of effects in response to genetic variation within lipid homeostatic
      genes.

PMID- 17015038
TI  - Mechanism of HBD-3 deficiency in atopic dermatitis.
AB  - Extrinsic atopic dermatitis (EAD) and intrinsic atopic dermatitis (IAD) patients
      suffer from recurrent bacterial and viral infections. In this study, we
      demonstrate significantly decreased expression of human beta defensin (HBD)-3, a
      potent antimicrobial peptide (AMP), in lesional skin of both IAD (p<0.01) and EAD
      patients (p<0.01), as compared to psoriasis patients. Using primary keratinocytes
      from EAD and IAD patients, we determined that the deficiency in HBD-3 expression
      is an acquired rather than a constitutive defect. Furthermore, we demonstrate the
      down-regulatory effect of IL-4, IL-10, and IL-13 - which are over-expressed in
      the skin of AD patients - on HBD-3 expression in keratinocytes. Additionally,
      treatment of EAD skin explants with antibodies against IL-4, IL-10, and IL-13
      augmented the expression of HBD-3. These studies suggest that neutralizing the
      Th2 cytokine milieu in AD skin may augment the innate immune response against
      bacterial and viral pathogens.

PMID- 17015039
TI  - Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene
      into nigral dopamine neurons of hemiparkinsonian rats.
AB  - Recently we showed that the neurotensin polyplex is a nanoparticle carrier system
      that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report
      its first practical application in experimental parkinsonism, which consisted of
      transfecting dopamine neurons with the gene coding for human glial cell line
      derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a
      single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the
      striatum. We showed that transfection of the hGDNF gene into the substantia nigra
      of rats 1 week after the neurotoxin injection produced biochemical, anatomical,
      and functional recovery from hemiparkinsonism. RT-PCR analysis showed mRNA
      expression of exogenous hGDNF in the transfected substantia nigra. Western blot
      analysis verified transgene expression by recognizing the flag epitope added at
      the C-terminus of the hGDNF polypeptide, which was found mainly in dopamine
      neurons by double immunofluorescence techniques. These data indicate that the
      neurotensin polyplex holds great promise for the neuroprotective therapy of
      Parkinson disease.

PMID- 17015040
TI  - Intracardiac echocardiography to guide myocardial biopsy of a primary cardiac
      tumour.
AB  - A 61-year-old man presented with recurrent ventricular tachycardia (left bundle
      branch block morphology, superior axis). Magnetic resonance imaging (Fig. 1) and
      contrast-enhanced transthoracic echocardiography (Fig. 2) demonstrated an ill
      defined mass in the right heart along the free wall of the right atrium,
      involving the tricuspid valve and extending into the right ventricle. Extensive
      investigation showed no evidence of extra-cardiac involvement and a tissue
      diagnosis was recommended. Accordingly, we elected to proceed to myocardial
      biopsy and, to facilitate accurate tissue localisation, we performed the
      procedure under guidance with intracardiac echocardiography.

PMID- 17015041
TI  - Sensory and biomechanical characterization of two painful syndromes in the heel.
AB  - This study evaluated sensory and biomechanical assets in 2 heel pain conditions
      with similar symptoms, entrapment syndrome of the nerve to abductor digiti quinti
      and myofascial syndrome of abductor hallucis. Thirty-three patients with
      unilateral heel pain and 20 asymptomatic subjects underwent pressure pain
      threshold measurement in the painful area in site A (medial process of calcaneal
      tuberosity, trigger point site of abductor hallucis) and site B (1 cm posteriorly
      to site A, where the nerve to abductor digiti quinti becomes most superficial)
      and contralaterally; electroneurography of posterior tibial nerve; evaluation of
      ground-foot reaction on a dynamic platform. Eighteen patients had electric shock
      type pain (entrapment syndrome, Group 1), 15 had cramp-like pain (myofascial
      syndrome, Group 2). Pain thresholds on the affected side versus contralaterally
      were significantly lower in site B in Group 1 and in site A in Group 2 (P <
      .001). Nerve conduction velocity was slightly reduced in Group 1 (P = .05).
      Ground-foot reaction was significantly altered on the affected side in all
      patients versus asymptomatic subjects; a significant difference between the 2
      sides was found for peak of force (F1) in Group 1 and for all parameters except
      temporal phase of peak of force (TF3) (P = .05) for Group 2 (P < .0001). The
      different sensory and biomechanical patterns of the 2 examined syndromes help the
      differential diagnosis and consequent therapeutic approach. PERSPECTIVE: This
      study shows different sensory and biomechanical patterns in 2 algogenic
      conditions of the heel with similar pain location. These distinct patterns
      reflect different pathophysiologic mechanisms in the 2 cases, which has a
      potential significant impact on treatment.

PMID- 17015042
TI  - Mycobacterium marinum produces long-term chronic infections in medaka: a new
      animal model for studying human tuberculosis.
AB  - Human infection by Mycobacterium tuberculosis is endemic, with approximately 2
      billion infected and is the most common cause of adult death due to an infectious
      agent. Because of the slow growth rate of M. tuberculosis and risk to
      researchers, other species of Mycobacterium have been employed as alternative
      model systems to study human tuberculosis (TB). Mycobacterium marinum may be a
      good surrogate pathogen, conferring TB-like chronic infections in some fish.
      Medaka (Oryzias latipes) has been established for over five decades as a
      laboratory fish model for toxicology, genotoxicity, teratogenesis,
      carcinogenesis, classical genetics and embryology. We are investigating if medaka
      might also serve as a host for M. marinum in order to model human TB. We show
      that both acute and chronic infections are inducible in a dose dependent manner.
      Colonization of target organs and systemic granuloma formation has been
      demonstrated through the use of histology. M. marinum expressing green
      fluorescent protein (Gfp) was used to monitor bacterial colonization of these
      organs in fresh tissues as well as in intact animals. Moreover, we have employed
      the See-Through fish line, a variety of medaka devoid of major pigments, to
      monitor real-time disease progression, in living animals. We have also compared
      the susceptibility of another prominent fish model, zebrafish (Danio rerio), to
      our medaka-M. marinum model. We determined the course of infections in zebrafish
      is significantly more severe than in medaka. Together, these results indicate
      that the medaka-M. marinum model provides unique advantages for studying chronic
      mycobacteriosis.

PMID- 17015043
TI  - Predictors of attendance and dropout at the Lung Health Study 11-year follow-up.
AB  - Participant attrition and attendance at follow-up were examined in a multicenter,
      randomized, clinical trial. The Lung Health Study (LHS) enrolled a total of 5887
      adults to examine the impact of smoking cessation coupled with the use of an
      inhaled bronchodilator on chronic obstructive pulmonary disease (COPD). Of the
      initial LHS 1 volunteers still living at the time of enrolment in LHS 3 (5332),
      4457 (84%) attended the LHS 3 clinic visit, a follow-up session to determine
      current smoking status and lung function. The average period between the
      beginning of LHS 1 and baseline interview for LHS 3 was 11 years. In univariate
      analyses, attenders were older, more likely female, more likely to be married,
      smoked fewer cigarettes per day, and were more likely to have children who smoked
      at the start of LHS 1 than non-attenders. Attenders were also less likely to
      experience respiratory symptoms, such as cough, but had decreased baseline lung
      function compared with non-attenders. Volunteers recruited via mass mailing were
      more likely to attend the long-term follow-up visit. Those recruited by public
      site, worksite, or referral methods were less likely to attend. In multivariate
      models, age, gender, cigarettes smoked per day, married status, and whether
      participants' children smoked were identified as significant predictors of
      attendance versus non-attendance at LHS 3 using stepwise logistic regression.
      Treatment condition (smoking intervention or usual care) was not a significant
      predictor of attendance at LHS 3. Older females who smoked less heavily were most
      likely to participate. These findings may be applied to improve participant
      recruitment and retention in future clinical trials.

PMID- 17015044
TI  - Effects of Type II diabetes on muscle microvascular oxygen pressures.
AB  - We tested the hypothesis that muscle microvascular O2 pressure (PmvO2; reflecting
      the O2 delivery (QO2) to O2 uptake (VO2) ratio) would be lowered in the
      spinotrapezius muscle of Goto-Kakizaki (GK) Type II diabetic rats (n=7) at rest
      and during twitch contractions when compared to control (CON; n=5) rats. At rest,
      PmvO2 was lower in GK versus CON rats (CON: 29+/-2; GK: 18+/-2Torr; P<0.05). At
      the onset of contractions, GK rats evidenced a faster change in PmvO2 than CON
      (i.e., time constant (tau); CON: 16+/-4; GK: 6+/-2s; P<0.05). In contrast to the
      monoexponential fall in PmvO2 to the steady-state level seen in CON, GK rats
      exhibited a biphasic PmvO2 response that included a blunted (or non-existent)
      PmvO2 decrease followed by recovery to a steady-state PmvO2 that was at, or
      slightly above, resting values. Compared with CON, this decreased PmvO2 across
      the transition to a higher metabolic rate in Type II diabetes would be expected
      to impair blood-muscle O2 exchange and contractile function.

PMID- 17015045
TI  - Thermal stability landscape for Klenow DNA polymerase as a function of pH and
      salt concentration.
AB  - The thermal denaturation of Klenow DNA polymerase has been characterized over a
      wide variety of solution conditions to obtain a relative stability landscape for
      the protein. Measurements were conducted utilizing a miniaturized fluorescence
      assay that measures Tm based on the increase in the fluorescence of 1,8
      anilinonaphthalene sulfonate (ANS) when the protein denatures. The melting
      temperature (Tm) for Klenow increases as the salt concentration is increased and
      as the pH is decreased. Klenow's Tm spans a range of over 20 degrees C, from 40
      to 62 degrees C, depending upon the solution conditions. The landscape reconciles
      and extends previously measured Tm values for Klenow. Salt effects on the
      stability of Klenow show strong cation dependence overlaid onto a more typical
      Hofmeister anion type dependence. Cationic stabilization of proteins has been far
      less frequently documented than anionic stabilization. The monovalent cations
      tested stabilize Klenow with the following hierarchy: NH4+>Na+>Li+>K+. Of the
      divalent cations tested: Mg+2 and Mn+2 significantly stabilize the protein, while
      Ni+2 dramatically destabilizes the protein. Stability measurements performed in
      combined Mg+2 plus Na+ salts suggest that the stabilizing effects of these
      monovalent and divalent cations are synergistic. The cationic stabilization of
      Klenow can be well explained by a model postulating dampening of repulsion within
      surface anionic patches on the protein.

PMID- 17015046
TI  - The analysis of histone modifications.
AB  - The biological function of many proteins is often regulated through
      posttranslational modifications (PTMs). Frequently different modifications
      influence each other and lead to an intricate network of interdependent
      modification patterns that affect protein-protein interactions, enzymatic
      activities and sub-cellular localizations. One of the best-studied class of
      proteins that is affected by PTMs and combinations thereof are the histone
      molecules. Histones are very abundant, small basic proteins that package DNA in
      the eukaryotic nucleus to form chromatin. The four core-histones are densely
      modified within their first 20-40 N-terminal amino acids, which are highly
      evolutionary conserved despite playing no structural role. The modifications are
      thought to constitute a histone code that is used by the cell to encrypt various
      chromatin conformations and gene expression states. The analysis of modified
      histones can be used as a model to dissect complex modification patterns and to
      investigate their molecular functions. Here we review techniques that have been
      used to decipher complex histone modification patterns and discuss the
      implication of these findings for chromatin structure and function.

PMID- 17015047
TI  - BcIV, a new paralyzing peptide obtained from the venom of the sea anemone
      Bunodosoma caissarum. A comparison with the Na+ channel toxin BcIII.
AB  - Sea anemones produce a wide variety of biologically active compounds, such as the
      proteinaceous neurotoxins and cytolysins. Herein we report a new peptide,
      purified to homogeneity from the neurotoxic fraction of B. caissarum venom, by
      using gel filtration followed by rp-HPLC, naming it as BcIV. BcIV is a 41 amino
      acid peptide (molecular mass of 4669 amu) possessing 6 cysteines covalently
      linked by three disulfide bonds. This toxin has 45 and 48% of identity when
      compared to APETx1 and APETx2 from Anthopleura elegantissima, respectively, and
      42% of identity with Am-II and BDS-I and-II obtained from Antheopsis maculata and
      Anemonia sulcata, respectively. This neurotoxin presents only a weak-paralyzing
      action (minimal Lethal Dose close to 2000 microg/kg) in swimming crabs
      Callinectes danae. This appears to be a different effect to that caused by the
      type 1 sea anemone toxin BcIII that is lethal to the same animals at lower doses
      (LD50=219 microg/kg). Circular dichroism spectra of BcIII and BcIV show a high
      content of beta-strand secondary structure in both peptides, very similar to type
      1 sodium channel toxins from various sea anemones, and to APETx1 and APETx2 from
      A. elegantissima, a HERG channel modulator and an ASIC3 inhibitor, respectively.
      Interestingly, BcIII and BcIV have similar effects on the action potential of the
      crab leg nerves, suggesting the same target in this tissue. As BcIII was
      previously reported as a Na+ channel effector and BcIV is inactive over Na+
      currents of mammalian GH3 cells, we propose a species-specific action for this
      new molecule. A molecular model of BcIV was constructed using the structure of
      the APETx1 as template and putative key residues are discussed.

PMID- 17015048
TI  - Brainstem auditory evoked response in neonatal neurology.
AB  - Over the last three decades, the brainstem auditory evoked response (BAER) has
      been used to assess functional integrity and development of the auditory system
      and the brain in conditions that affect the brainstem auditory pathway. As a non
      invasive objective test, BAER is particularly suitable in very young or sick
      infants. It is the major tool to detect hearing impairment in high-risk infants,
      and a component in universal hearing screening. BAER is also a valuable adjunct
      to detect neurological impairment in many developmental disorders and functional
      abnormalities in a range of neurological diseases. The maximum length sequence
      (MLS) technique has recently been incorporated into neonatal BAER study. Recent
      results indicate that the MLS has the potential to improve the diagnostic value
      of BAER in some clinical situations, although the wider utility of this relative
      new technique remains to be further explored.

PMID- 17015050
TI  - Determinants of the rate of nicotine metabolism and effects on smoking behavior.
AB  - BACKGROUND: Studies on cytochrome P450 (CYP) 2A6 suggest that genotype affects
      the rate of nicotine metabolism and, consequently, cigarette consumption.
      However, known alleles of CYP2A6 associated with fast or slow metabolism are
      relatively uncommon, and there remains considerable variation in metabolic
      activity among those with presumed wild-type CYP2A6 alleles, suggesting that
      other genetic or environmental factors also influence the rate of nicotine
      metabolism. METHODS: We investigated determinants of the rate of nicotine
      metabolism and effects on smoking behavior in a United Kingdom cohort who
      participated in a placebo-controlled trial of smoking cessation via nicotine
      replacement therapy. Those who continued to smoke cigarettes at the 8-year follow
      up formed our study group (N = 545). The ratio of the nicotine metabolite trans
      3'-hydroxycotinine to cotinine in plasma was used as an index of CYP2A6 activity
      and thus as a marker of the rate of nicotine metabolism. RESULTS: The nicotine
      metabolite ratio was associated with sex (P < .0001), CYP2A6 genotype (*1B, *2,
      *4, *9, and *12) (P < .0001), CYP2B6 haplotype (*4-dominant) (P = .02), plasma
      nicotine concentration (P < .0001), and age (P = .02) but was not associated with
      dependence score (P > .20). The ratio also predicted the number of cigarettes
      smoked at will per day, although the association was weak (F(1, 492) = 4.05, P =
      .04). CONCLUSION: In this cohort the rate of nicotine metabolism is related to
      age, sex, CYP2A6 genotype, and CYP2B6 genotype and may affect the level of
      tobacco consumption.

PMID- 17015049
TI  - Orosomucoid (alpha1-acid glycoprotein) plasma concentration and genetic variants:
      effects on human immunodeficiency virus protease inhibitor clearance and cellular
      accumulation.
AB  - BACKGROUND AND OBJECTIVE: Protease inhibitors are highly bound to orosomucoid
      (ORM) (alpha1-acid glycoprotein), an acute-phase plasma protein encoded by 2
      polymorphic genes, which may modulate their disposition. Our objective was to
      determine the influence of ORM concentration and phenotype on indinavir,
      lopinavir, and nelfinavir apparent clearance (CL(app)) and cellular accumulation.
      Efavirenz, mainly bound to albumin, was included as a control drug. METHODS:
      Plasma and cells samples were collected from 434 human immunodeficiency virus
      infected patients. Total plasma and cellular drug concentrations and ORM
      concentrations and phenotypes were determined. RESULTS: Indinavir CL(app) was
      strongly influenced by ORM concentration (n = 36) (r2 = 0.47 [P = .00004]),
      particularly in the presence of ritonavir (r2 = 0.54 [P = .004]). Lopinavir
      CL(app) was weakly influenced by ORM concentration (n = 81) (r2 = 0.18 [P =
      .0001]). For both drugs, the ORM1 S variant concentration mainly explained this
      influence (r2 = 0.55 [P = .00004] and r2 = 0.23 [P = .0002], respectively).
      Indinavir CL(app) was significantly higher in F1F1 individuals than in F1S and SS
      patients (41.3, 23.4, and 10.3 L/h [P = .0004] without ritonavir and 21.1, 13.2,
      and 10.1 L/h [P = .05] with ritonavir, respectively). Lopinavir cellular exposure
      was not influenced by ORM abundance and phenotype. Finally, ORM concentration or
      phenotype did not influence nelfinavir (n = 153) or efavirenz (n = 198)
      pharmacokinetics. CONCLUSION: ORM concentration and phenotype modulate indinavir
      pharmacokinetics and, to a lesser extent, lopinavir pharmacokinetics but without
      influencing their cellular exposure. This confounding influence of ORM should be
      taken into account for appropriate interpretation of therapeutic drug monitoring
      results. Further studies are needed to investigate whether the measure of unbound
      drug plasma concentration gives more meaningful information than total drug
      concentration for indinavir and lopinavir.

PMID- 17015051
TI  - Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in
      pediatric living-donor liver transplant recipients.
AB  - OBJECTIVE: Our objective was to investigate the population pharmacokinetics of
      tacrolimus in pediatric living-donor liver transplant recipients and examine the
      effects of the multidrug resistance 1 (MDR1) gene and the cytochrome P450 (CYP)
      genes CYP3A4 and CYP3A5 on the oral clearance of tacrolimus. METHODS: Data were
      collected retrospectively from 130 de novo pediatric liver transplant recipients
      treated with tacrolimus during the first 50 postoperative days. Pharmacogenomic
      data including both the CYP3A5*3 polymorphism and messenger ribonucleic acid
      (mRNA) expression levels of MDR1, CYP3A4, and CYP3A5 in the native intestine and
      the graft liver at transplantation were obtained from 65 of the recipients.
      Population pharmacokinetic analysis was performed with the nonlinear mixed
      effects modeling program NONMEM to estimate population mean parameters of
      apparent clearance (CL/F) and apparent volume of distribution (V/F). RESULTS:
      Both CL/F and V/F were allometrically related to body weight, and CL/F decreased
      when the AST value was elevated. CL/F increased linearly in the immediate
      postoperative period but did not change with time after postoperative day 21. The
      intestinal MDR1 mRNA level significantly influenced the initial CL/F (P < .005).
      Furthermore, the increase in CL/F over time was 2 times higher (95% confidence
      interval, 1.19-2.81 times; P < .005) in recipients of a CYP3A5*1-carrying graft
      liver than in patients with the hepatic CYP3A5*3/*3 genotype. The Bayesian
      prediction for tacrolimus concentrations was not significantly biased on any
      postoperative day, and the mean absolute prediction error was lower than 3 ng/mL
      after the first 2 weeks of transplantation. CONCLUSIONS: The enterocyte MDR1 mRNA
      level and the CYP3A5*1 allele in the graft liver contribute differently to the
      interindividual variability in the oral clearance of tacrolimus after living
      donor liver transplantation.

PMID- 17015052
TI  - A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in
      vitamin K epoxide reductase complex and cytochrome P450 2C9.
AB  - INTRODUCTION: Because of the unique lack of genetic diversity despite the
      multiethnicity in the Asian population, we hypothesize that single-nucleotide
      polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9*3) and vitamin K epoxide
      reductase complex subunit 1 (VKORC1) at position 381, used to infer
      VKORC1haplotype in combination with demographic factors, can accurately predict
      warfarin doses. The aims of this study were to derive a pharmacogenetics-based
      dosing algorithm by use of retrospective information and to validate it through a
      data-splitting method in a separate cohort of equal size. METHODS: We used 215
      records of warfarin patients recruited into a CYP2C9/VKORC1 genotyping study to
      perform this analysis. Univariate analyses for individual predictors, including
      age, weight, gender, serum albumin concentration, ethnic group, international
      normalized ratio, and CYP2C9 and VKORC1 381 genotypes, were conducted to select
      variables with P < .1 for further inclusion into the multivariate regression
      analysis. In the final model only predictors reaching a statistical significance
      of P < .05 were retained. RESULTS: Data from 107 subjects undergoing maintenance
      warfarin therapy with an international normalized ratio stabilized between 2 and
      3 were used to derive the final model, as an exponential function of age, weight,
      CYP2C9*3 allele, and VKORC1 381 CC and TC genotypes, and this model accounted for
      60.2% of the variability in daily warfarin dose requirement. The model was
      validated in a separate cohort of 108 subjects and showed a mean underestimation
      of 0.23 +/- 1.21 mg/d. CONCLUSION: Warfarin dose requirements in Asians can be
      accurately predicted by use of a combination of patient demographics and a
      simplified genotyping approach for single variants in CYP2C9 and VKORC1.

PMID- 17015053
TI  - SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not
      fluvastatin.
AB  - OBJECTIVE: Pravastatin is a hydrophilic substrate and fluvastatin a lipophilic
      substrate of the hepatic uptake transporter organic anion transporting
      polypeptide 1B1 encoded by SLCO1B1. Our aim was to compare the effects of SLCO1B1
      polymorphism on the pharmacokinetics of pravastatin and fluvastatin. METHODS: We
      recruited 4 healthy volunteers (3 men and 1 woman) with the homozygous SLCO1B1
      c.521CC genotype, 12 (7 men and 5 women) with the heterozygous c.521TC genotype,
      and 16 (8 men and 8 women) with the homozygous c.521TT genotype (control
      subjects). In a crossover study each subject ingested a single 40-mg dose of
      fluvastatin and pravastatin with a washout period of at least 1 week. Plasma
      fluvastatin and pravastatin concentrations were measured for 12 hours. RESULTS:
      In men with the c.521CC genotype, the mean peak concentration in plasma and area
      under the plasma concentration-time curve from time 0 to infinity of pravastatin
      were 274% (95% confidence interval [CI], 92%-456%; P = .001) and 232% (95% CI,
      74%-391%; P = .002) greater than those in men with the c.521TT genotype and 120%
      (95% CI, 11%-230%; P = .026) and 102% (95% CI, 3%-200%; P = .040) greater than
      those in men with the c.521TC genotype. In addition, women with the c.521TT
      genotype had a 147% (95% CI, 12%-281%; P = .028) greater peak concentration in
      plasma and a 142% (95% CI, 7%-242%; P = .034) greater area under the plasma
      concentration-time curve from time 0 to infinity than men with the c.521TT
      genotype. The pharmacokinetic variables of pravastatin were approximately similar
      among women with different SLCO1B1 genotypes. No significant differences were
      seen in the pharmacokinetics of fluvastatin between subjects with different
      SLCO1B1 genotypes or between the sexes. CONCLUSIONS: SLCO1B1 polymorphism has a
      large effect on the pharmacokinetics of pravastatin but not fluvastatin. This
      suggests that the lipophilic fluvastatin can penetrate the hepatocyte plasma
      membrane via passive diffusion or that uptake transporters other than organic
      anion transporting polypeptide 1B1 mainly mediate its hepatic uptake. Moreover,
      the results suggest that sex may affect the pharmacokinetics of pravastatin and
      possibly the functional consequences of SLCO1B1 polymorphism.

PMID- 17015054
TI  - MDR1 gene polymorphisms are associated with neuropsychiatric adverse effects of
      mefloquine.
AB  - BACKGROUND: Mefloquine, a drug used for treatment and prophylaxis of malaria, is
      known for its neuropsychiatric adverse effects. We hypothesized that
      neuropsychiatric adverse effects of mefloquine are associated with polymorphisms
      in the MDR1/ABCB1 gene that encodes for the efflux pump P-glycoprotein. METHODS:
      The association between MDR1 C1236T, G2677T, and C3435T single-nucleotide
      polymorphisms and the occurrence of neuropsychiatric adverse effects was examined
      in a prospective cohort study of 89 healthy white travelers taking mefloquine.
      RESULTS: Of the subjects, 27 (28%) reported neuropsychiatric adverse effects,
      women significantly more frequently than men. Allele frequencies of the C1236T,
      G2677T, and C3435T polymorphisms were similar to those found in other white
      populations, and there was no significant association between any of the
      individual polymorphisms and neuropsychiatric adverse effects. However, women
      with the 1236TT, 2677TT, and 3435TT genotypes had a higher risk of
      neuropsychiatric adverse effects than the reference groups of women with
      heterozygous and homozygous CC or GG genotypes, with odds ratios of 6.3 (95%
      confidence interval [CI], 1.1-36.9), 10.5 (95% CI, 1.1-100.6), and 5.4 (95% CI,
      1.1-30.0), respectively. The association for women homozygous for the 1236-2677
      3435 TTT haplotype was even stronger (P = .004) than the effect of any of the
      individual polymorphisms. No associations with mefloquine blood levels were
      observed. CONCLUSION: In this study the MDR1 1236TT, 2677TT, and 3435TT
      genotypes, along with the 1236-2677-3435 TTT haplotype, were associated with
      neuropsychiatric adverse effects of mefloquine in women. MDR1 polymorphisms may
      play an important role in predicting the occurrence of neuropsychiatric adverse
      effects of mefloquine, particularly in female travelers.

PMID- 17015055
TI  - The thiopurine methyltransferase genetic polymorphism is associated with
      thioguanine-related veno-occlusive disease of the liver in children with acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: Thiopurine metabolism was investigated in children with acute
      lymphoblastic leukemia treated in the United Kingdom Medical Research Council
      trial ALL97. This trial compared the efficacy and toxicity of thioguanine (INN,
      thioguanine) versus mercaptopurine. METHODS: Consecutive children were randomized
      to receive thioguanine or mercaptopurine during maintenance chemotherapy.
      Toxicity data were collected by an adverse event-reporting system with follow-up
      questionnaires. Red blood cell thiopurine methyltransferase (TPMT) activity and
      thioguanine nucleotide concentrations were measured by standard techniques.
      RESULTS: Of the children, 748 were randomized to thioguanine and 744 were
      randomized to mercaptopurine. There was no difference in the event-free survival
      rate between the 2 groups (80% and 81%, respectively, at 5 years). Thioguanine
      was associated with veno-occlusive disease (VOD) of the liver in 95 children, and
      persistent splenomegaly as a result of portal hypertension developed in 43
      children. TPMT activity was significantly lower in the children in whom VOD
      developed, with a median of 13.4 U (range, 5.8-23 U) compared with 15.2 U (range,
      5.3-27) in a control group of 161 leukemia patients in whom VOD did not develop
      (median difference, 1.8 U; 95% confidence interval, 0.9-2.7 U; P = .0001). TPMT
      activity in children with persistent splenomegaly was also lower than that in
      control subjects (median difference, 1.6 U; 95% confidence interval, 0.3-2.8 U; P
      = .012). There was no difference in red blood cell thioguanine nucleotide
      concentrations. CONCLUSIONS: Thioguanine was associated with liver damage in 11%
      of children randomized to thioguanine without an improvement in event-free
      survival rate. The association of lower TPMT activity with thioguanine-related
      liver damage could provide a means of identifying at-risk patients.

PMID- 17015056
TI  - A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity.
AB  - BACKGROUND AND OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) plays a key role
      in the catabolism of 5-fluorouracil (5-FU) to 5-fluoro-5,6-dihydrouracil (5
      FDHU), and as such, an impairment of DPD has been recognized as an important
      factor for altered 5-FU and 5-FDHU pharmacokinetics, predisposing patients to the
      development of severe 5-FU-associated toxicity. Our objectives were to avoid
      severe 5-FU toxicities in patients with greatly impaired 5-FU and 5-FDHU
      pharmacokinetics after the administration of a reduced test dose of 5-FU and to
      investigate possible 5-FU or 5-FDHU pharmacokinetic parameters of the test dose
      related to the most common drug toxicities that affect patients after the first
      cycle of 5-FU chemotherapy. METHODS: Pharmacokinetics of 5-FU/5-FDHU and DPD
      activity in peripheral blood mononuclear cells (PBMCs) were examined in 188
      gastrointestinal cancer patients given a test dose of 5-FU, 250 mg/m2, 2 weeks
      before starting the planned 5-FU treatment of 370 mg/m2 plus l-folinic acid, 100
      mg/m2, for 5 days every 4 weeks. Drug levels were examined by HPLC, and
      toxicities were graded according to World Health Organization criteria. RESULTS:
      The 5-FU test dose was well tolerated in all patients. Of 188 patients, 3 (1.6%)
      had marked alterations of 5-FU/5-FDHU pharmacokinetics (ie, 5-FU half-life [t(1/2
      beta)] >5 hours, 5-FU total body clearance [CL(TB)] <1 L x h(-1) x m(-2), and 5
      FDHU time to reach maximum plasma concentration [t max] > or = 45 minutes); they
      were excluded from 5-FU treatments and treated with irinotecan, which was well
      tolerated. The plasma disposition of 5-FU in the remaining 185 patients revealed
      an area under the curve (AUC) of 3.73 +/- 2.18 h x microg/mL (mean +/- SD),
      maximum plasma concentration (Cmax) of 16.78 +/- 8.61 microg/mL, and t(1/2 beta)
      of 0.16 +/- 0.15 hour, whereas the CL(TB) was 65.67 +/- 31.86 L x h(-1) x m(-2).
      The 5-FDHU plasma profile showed a Cmax value of 3.64 +/- 1.94 microg/mL, whereas
      the t max value was 26.63 +/- 10.06 minutes, with an AUC value of 3.71 +/- 1.90 h
      x microg/mL. The PBMC DPD activity was 202.15 +/- 141.14 pmol 5-FDHU x min(-1) x
      mg(-1) protein (95% confidence interval, 165-239.3 pmol 5-FDHU x min(-1) x mg(-1)
      protein). A significant correlation between 5-FU AUC and 5-FDHU AUC was found (r
      = 0.5492, P < .0001), whereas a weaker correlation between PBMC DPD activity and
      both 5-FDHU AUC (r = 0.328, P = .0121) and 5-FDHU Cmax (r = 0.369, P = .0044) was
      found. Interestingly, no relationships between PBMC DPD activity and common
      toxicities were found, whereas 5-FDHU t max values greater than 30 minutes were
      associated with the risk of moderate to severe neutropenia and diarrhea (P =
      .0323 and P = .0138, respectively; chi-square test). CONCLUSIONS: This study
      suggests a successful approach for preventing severe or life-threatening
      toxicities in gastrointestinal cancer patients who are candidates for standard 5
      FU treatment by analyzing the 5-FU and 5-FDHU pharmacokinetic parameters after
      the administration of a reduced 5-FU test dose.

PMID- 17015057
TI  - Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced
      osteonecrosis.
AB  - BACKGROUND: Osteonecrosis of the femoral head (ONFH) is one of the major side
      effects of corticosteroid therapy. Because corticosteroids are metabolized by
      hepatic cytochrome P450 (CYP) 3A, a low endogenous activity of this enzyme may
      contribute to the pathogenesis of ONFH. The purpose of this study was to examine
      the possible association of hepatic CYP3A activity and the susceptibility to ONFH
      in patients treated with corticosteroids. METHODS: In this prospective controlled
      study we measured the clearance of intravenous midazolam (0.25 mg/kg) to estimate
      hepatic CYP3A activity in patients with steroid-induced ONFH (n = 26), patients
      with alcohol-related ONFH (n = 29), and non-ONFH control patients (n = 75)
      undergoing orthopedic surgery. Midazolam clearance was compared between the
      groups, and the relationship between the level of hepatic CYP3A activity and the
      prevalence of ONFH was evaluated by multivariate analysis. RESULTS: Midazolam
      clearance in patients with steroid-induced ONFH was significantly lower than that
      in control patients and patients with alcohol-related ONFH (7.7 +/- 1.8 mL x kg(
      1) x min(-1) versus 11.4 +/- 3.5 mL x kg(-1) x min(-1) and 10.5 +/- 2.8 mL x kg(
      1) x min(-1), respectively; P < .001). Patients with low midazolam clearance
      (<9.5 mL x kg(-1) x min(-1)) had a 9-fold greater risk for steroid-induced ONFH
      (adjusted odds ratio, 9.08 [95% confidence interval, 2.79-29.6]; P < .001).
      Midazolam clearance did not show a significant correlation with the prevalence of
      alcohol-related ONFH. CONCLUSIONS: Low hepatic CYP3A activity may significantly
      contribute to the risk for steroid-induced ONFH.

PMID- 17015058
TI  - Human pharmacology of the methamphetamine stereoisomers.
AB  - OBJECTIVE: To help predict the consequences of precursor regulation, we compared
      the pharmacokinetics and pharmacodynamics of the methamphetamine (INN,
      metamfetamine) stereoisomers. METHODS: In this study 12 methamphetamine abusers
      received intravenous d-methamphetamine (0.25 and 0.5 mg/kg), l-methamphetamine
      (0.25 and 0.5 mg/kg), racemic methamphetamine (0.5 mg/kg), or placebo with the
      use of a 6-session, double-blind, placebo-controlled, balanced crossover design.
      Pharmacokinetic measures (including area under the plasma concentration-time
      curve [AUC], elimination half-life, systemic clearance, apparent volume of
      distribution during the elimination phase, and apparent bioavailability) and
      pharmacodynamic measures (including heart rate, blood pressure, respiratory rate,
      and visual analog scale ratings for "intoxication," "good drug effect," and "drug
      liking") were obtained. RESULTS: Pharmacokinetic parameters for the individual
      enantiomers given separately were similar, with dose-proportional increases in
      AUC and maximum plasma concentration. After racemate administration, the AUC for
      d-methamphetamine was 30% smaller than that for l-methamphetamine (P = .0085).
      The elimination half-lives were longer for l-methamphetamine (13.3-15.0 hours)
      than for d-methamphetamine (10.2-10.7 hours) (P < .0001). Compared with placebo,
      d-methamphetamine (0.25 mg/kg, 0.5 mg/kg, and racemic) increased the heart rate
      (P < .0001), blood pressure (P < .0001), and respiratory rate (P < .05), and this
      increase lasted for 6 hours. The peak heart rate changes after racemic
      methamphetamine and 0.5 mg/kg d- and l-methamphetamine were similar (18.7 +/-
      23.4 beats/min, 13.5 +/- 18.5 beats/min, and 10.7 +/- 10.2 beats/min,
      respectively), but racemic methamphetamine and 0.5 mg/kg d-methamphetamine
      increased systolic blood pressure more than 0.5 mg/kg l-methamphetamine (33.4 +/-
      17.8 beats/min and 34.5 +/- 18.9 beats/min, respectively, versus 19.5 +/- 11.3
      beats/min; P < .01). l-Methamphetamine, 0.5 mg/kg, was psychoactive, producing
      peak intoxication (46.0 +/- 35.3 versus 30.3 +/- 24.9) and drug liking (47.7 +/-
      35.1 versus 28.6 +/- 24.8) ratings similar to 0.5 mg/kg d-methamphetamine, but
      the effects of l-methamphetamine dissipated more quickly (approximately 3 hours
      versus 6 hours). The effects of 0.25 mg/kg l-methamphetamine were similar to
      those of placebo. Racemic methamphetamine was similar to d-methamphetamine with
      regard to most pharmacodynamic measures. CONCLUSION: The pharmacokinetics of the
      methamphetamine enantiomers are similar, but there are substantial
      pharmacodynamic differences between the isomers. At high doses, l-methamphetamine
      intoxication is similar to that of d-methamphetamine, but the psychodynamic
      effects are shorter-lived and less desired by abusers. Racemic and d
      methamphetamine have similar effects and would be expected to have comparable
      abuse liabilities.

PMID- 17015059
TI  - Erythromycin alters the pharmacokinetics of bromocriptine by inhibition of
      organic anion transporting polypeptide C-mediated uptake.

PMID- 17015060
TI  - Effect of S-1 on pharmacokinetics of irinotecan in a patient with colorectal
      cancer.

PMID- 17015062
TI  - Interdependence of virtual electrode polarization and conduction velocity during
      premature stimulation.
AB  - BACKGROUND: Fiber orientation in the heart plays a crucial role in the
      anisotropic nature of impulse propagation and the formation of virtual electrode
      polarization (VEP). The relationship between anisotropic conduction velocity and
      VEP is not fully understood. METHODS AND RESULTS: We recorded transmembrane
      potential from the surface of isolated rabbit hearts (N = 7) in the presence of
      15 mmol/L of diacetylmonoxime using a video imaging system. We paced each heart
      at a constant cycle length of 250 milliseconds and delivered a premature stimulus
      (S2) from the same unipolar electrode. The S2 pulses of either polarity were
      applied at various coupling intervals (CIs); S2 duration was 10 milliseconds and
      stimulus amplitude was 40 mA. Impulse propagation at 250 milliseconds occurred
      via elliptical waves with an anisotropy ratio (AR) of approximately 2.5. Owing to
      VEP, AR varied dramatically as a function of S2 polarity and CI. At intermediate
      CIs (approximately 150 milliseconds), AR was decreased by a factor of 3 for
      anodal stimulation and increased by a factor of 2 for cathodal stimulation. At
      slightly shorter CIs (approximately 115 milliseconds), impulse propagation was
      blocked, leading to unidirectional block and the initiation of reentrant
      arrhythmias. Conduction block always occurred along fibers for anodal stimulation
      and across fibers for cathodal stimulation. CONCLUSION: Fiber orientation plays a
      prominent role in impulse propagation during premature stimulation such as that
      which occurs during pacing of ventricular tachycardia and ventricular
      fibrillation. The interdependence of VEP and conduction velocity acts to
      dramatically alter AR and arrhythmogenesis.

PMID- 17015063
TI  - Improving automatic analysis of the electrocardiogram acquired during magnetic
      resonance imaging using magnetic field gradient artefact suppression.
AB  - The electrocardiogram (ECG) used for patient monitoring during magnetic resonance
      imaging (MRI) unfortunately suffers from severe artefacts. These artefacts are
      due to the special environment of the MRI. Modeling helped in finding solutions
      for the suppression of these artefacts superimposed on the ECG signal. After we
      validated the linear and time invariant model for the magnetic field gradient
      artefact generation, we applied offline and online filters for their suppression.
      Wiener filtering (offline) helped in generating reference annotations of the ECG
      beats. In online filtering, the least-mean-square filter suppressed the magnetic
      field gradient artefacts before the acquired ECG signal was input to the
      arrhythmia algorithm. Comparing the results of two runs (one run using online
      filtering and one run without) to our reference annotations, we found an eminent
      improvement in the arrhythmia module's performance, enabling reliable patient
      monitoring and MRI synchronization based on the ECG signal.

PMID- 17015064
TI  - Novel electrocardiogram configurations and transmission procedures in the
      prehospital setting: effect on ischemia and arrhythmia determination.
AB  - AIM: The aims of this report are to (1) describe a novel prehospital 12-lead
      electrocardiogram (ECG) configuration and transmission procedure used in the
      Synthesized Twelve-lead ST Monitoring and Real-time Tele-electrocardiography
      Study and to (2) report on the frequency of arrhythmias in field ECGs compared
      with the first hospital ECG. METHODS: The Synthesized Twelve-lead ST Monitoring
      and Real-time Tele-electrocardiography Study is a 5-year randomized clinical
      trial ending in 2008. All emergency vehicles responding to 911 calls in Santa
      Cruz County, Calif, have been equipped with portable monitor defibrillators with
      a special study software that (1) synthesizes a 12-lead ECG from 5 electrodes,
      (2) measures ST amplitudes in all 12 leads every 30 seconds, and (3)
      automatically transmits an ECG to the target emergency department if there is a
      change in ST amplitude of 200 microV in 1 lead or more or 100 microV in 2
      contiguous leads or more lasting 2.5 minutes. An initial ECG is transmitted by
      paramedics, which activates the software. Subsequent transmissions of ST event
      ECGs occur automatically without paramedic decision making. RESULTS: Prehospital
      ECGs had a greater frequency of arrhythmias than the first hospital ECG in the
      group as a whole (n = 433; 33.3% vs 28.9%; P < or = .001), as well as the
      subgroup with acute coronary syndrome (n = 185; 30.3% vs 26.5%; P < or = .001).
      More tachyarrhythmias occurred in the field and slightly more bradyarrhythmias
      occurred at the time of the first hospital ECG. CONCLUSIONS: Prehospital
      continuous 12-lead ST-segment ischemia monitoring with computer-assisted
      automatic mobile telephone transmission of ST event ECGs to the target hospital
      is feasible. More arrhythmias occur in the prehospital phase than are evident on
      the first hospital ECG.

PMID- 17015065
TI  - Electrophysiology of the electrocardiographic changes of atrial fibrillation.
AB  - The history of atrial fibrillation is described in terms of its
      electrocardiographic delineation, characteristics and clinical associations. The
      variant configurations are described and their relationship to rhythm duration
      and cardioversion success. The inter-relationship of fibrillation with flutter
      and their diagnostic differences are reviewed. The electrophysiologic basis of
      atrial remodeling is exemplified, together with its relationship to failure of
      rate adaptation of the atrial refractory period. Electric countershock causes an
      acute abbreviation of the atrial refractory period as does the induction of
      hyperthyroidism in the experimental animal. Current theories of the mechanism of
      fibrillation and the issue of originating pulmonary venous foci are reviewed. The
      lack of protection from ventricular fibrillation that exists with preexcitation
      via an accessory pathway is discussed in terms of the teleological role of
      orthograde downstream refractory periods.

PMID- 17015066
TI  - Optical imaging of arrhythmias in tissue culture.
AB  - BACKGROUND: Cardiac cell cultures are becoming an important experimental system
      of minimal complexity that captures many of the salient features of myocardial
      tissue function and are simple enough that tissue parameters can be controlled
      systematically. Fundamental mechanisms that underlie normal and pathological
      electrophysiology at the tissue level can be studied. Of particular interest are
      spiral waves, which underlie many tachyarrhythmias and fibrillation. METHODS:
      Methods of patterned growth were used to control tissue structure, and contact
      fluorescence imaging was used to visualize the spread of electrical waves in
      confluent monolayers of neonatal rat ventricular cells stained with voltage
      sensitive dye. RESULTS: Work is summarized regarding anisotropy, multiarmed
      spirals, cocultures of cardiac cells and skeletal myoblasts or mesenchymal stem
      cells, mechanical excitation, attachment of spiral waves to small anatomical
      obstacles, perturbation of spiral waves by external electric fields, and
      structure-based facilitation of spiral wave formation. CONCLUSIONS: The cultured
      cell monolayer is a contemporary experimental model encompassing great
      versatility for basic studies of wavefront propagation and cardiac arrhythmias.

PMID- 17015067
TI  - Biopotential fiber sensor.
AB  - We have developed a new biopotential fiber sensor (BFS) technology as an
      alternative to traditional wet-gel Ag/AgCl electrodes in long-term monitoring
      applications. Biopotential fiber sensor technology uses proprietary method of
      bonding copper sulfide to the surface of acrylic fibers, thus creating an
      electrically conductive medium (10(-1) ohms/cm). Surface modified bundles of
      acrylic fibers form stable biopotential sensors when doped with proprietary ink
      comprising organic acids and nano particles of Ag and AgCl. Biopotential fiber
      sensors are characterized by a small footprint 0.1 mm2 and low mass of 0.005 g.
      Biopotential fiber sensor systems are disposable 1-piece assemblies combining the
      functions of the electrodes, lead wires and a patient cable. METHODS: The
      electric performance characteristics of BFS were obtained according to American
      National Standards Institute/Association for the Advancement of Medical
      Instrumentation EC-12:2000 standard and compared with Ag/AgCl wet-gel electrodes.
      The noise characteristics were determined from 250 hours of 3-lead
      electrocardiographic (ECG) data recorded with BFS over a period of 10 days from
      healthy volunteers. RESULTS: The BFS direct current offset voltage was 0.11 mV
      and alternate current impedance at 10 Hz was 22 ohms. The sensors average
      longevity on the body surface with no detachments was at least 7 days. BFS
      demonstrated high immunity to motion and electric field-induced artifacts.
      CONCLUSIONS: Biopotential fiber sensors are well suited for routine long-term ECG
      monitoring applications because of increased patient comfort through integration
      of the electrode, lead wire, and a patient cable, which function into one
      disposable BFS fiber assembly. Biopotential fiber sensor have electrical
      characteristics comparable to Ag/AgCl wet electrodes. We observed an improved ECG
      signal quality, reduced frequent electrode detachments, reduced wire clutter and
      entanglement, and improved sensor adherence to the skin over longer periods of
      time.

PMID- 17015068
TI  - Implantable electrocardiographic monitoring--clinical experiences.

PMID- 17015069
TI  - Consideration of the 24-lead electrocardiogram to provide ST-elevation myocardial
      infarction equivalent criteria for acute coronary occlusion.

PMID- 17015070
TI  - St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of
      intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial
      apoptosis.
AB  - Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy,
      in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin,
      capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has
      anti-inflammatory activity, and our preliminary study in the rat and a pilot
      study in cancer patients found that treatment of SJW alleviated irinotecan
      induced diarrhea. In the present study, we investigated whether SJW modulated
      various pro-inflammatory cytokines including interleukins (IL-1beta, IL-2, IL-6),
      interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) and intestinal
      epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg
      for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg
      for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines
      including IL-1beta, IL-2, IL-6, IFN-gamma and TNF-alpha and intestinal epithelial
      apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW
      markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production
      of pro-inflammatory cytokines such as IL-1beta, IFN-gamma and TNF-alpha was
      significantly up-regulated in intestine. In the mean time, combined SJW
      significantly suppressed the intestinal epithelial apoptosis induced by CPT-11
      over days 5-11. In particular, combination of SJW significantly inhibited the
      expression of TNF-alpha mRNA in the intestine over days 5-11. In conclusion,
      inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis
      partly explained the protective effect of SJW against the intestinal toxicities
      induced by irinotecan. Further studies are warranted to explore the potential for
      STW as an agent in combination with chemotherapeutic drugs to lower their dose
      limiting toxicities.

PMID- 17015072
TI  - Emotion, motivation, and the brain: reflex foundations in animal and human
      research.
AB  - This review will focus on a motivational circuit in the brain, centered on the
      amygdala, that underlies human emotion. This neural circuitry of
      appetitive/approach and defensive/avoidance was laid down early in our
      evolutionary history in primitive cortex, sub-cortex, and mid-brain, to mediate
      behaviors basic to the survival of individuals and the propagation of genes to
      coming generations. Thus, events associated with appetitive rewards, or that
      threaten danger or pain, engage attention and prompt information gathering more
      so than other input. Motive cues also occasion metabolic arousal, anticipatory
      responses, and mobilize the organism to prepare for action. Findings are
      presented from research with animals, elucidating these psychophysiological
      (e.g., cardiovascular, neuro-humoral) and behavioral (e.g., startle potentiation,
      "freezing") patterns in emotion, and defining their mediating brain circuits.
      Parallel results are described from experiments with humans, showing similar
      activation patterns in brain and body in response to emotion cues, co-varying
      with participants' reports of affective valence and increasing emotional arousal.

PMID- 17015073
TI  - Emotion and attention: event-related brain potential studies.
AB  - Emotional pictures guide selective visual attention. A series of event-related
      brain potential (ERP) studies is reviewed demonstrating the consistent and robust
      modulation of specific ERP components by emotional images. Specifically, pictures
      depicting natural pleasant and unpleasant scenes are associated with an increased
      early posterior negativity, late positive potential, and sustained positive slow
      wave compared with neutral contents. These modulations are considered to index
      different stages of stimulus processing including perceptual encoding, stimulus
      representation in working memory, and elaborate stimulus evaluation. Furthermore,
      the review includes a discussion of studies exploring the interaction of
      motivated attention with passive and active forms of attentional control. Recent
      research is reviewed exploring the selective processing of emotional cues as a
      function of stimulus novelty, emotional prime pictures, learned stimulus
      significance, and in the context of explicit attention tasks. It is concluded
      that ERP measures are useful to assess the emotion-attention interface at the
      level of distinct processing stages. Results are discussed within the context of
      two-stage models of stimulus perception brought out by studies of attention,
      orienting, and learning.

PMID- 17015074
TI  - Implicit and explicit categorization of natural scenes.
AB  - Event-related potential (ERP) studies have consistently found that emotionally
      arousing (pleasant and unpleasant) pictures elicit a larger late positive
      potential (LPP) than neutral pictures in a window from 400 to 800 ms after
      picture onset. In addition, an early ERP component has been reported to vary with
      emotional arousal in a window from about 150 to 300 ms with affective, compared
      to neutral stimuli, prompting significantly less positivity over occipito
      temporal sites. Similar early and late ERP components have been found in explicit
      categorization tasks, suggesting that selective attention to target features
      results in similar cortical changes. Several studies have shown that the
      affective modulation of the LPP persisted even when the same pictures are
      repeated several times, when they are presented as distractors, or when
      participants are engaged in a competing task. These results indicate that
      categorization of affective stimuli is an obligatory process. On the other hand,
      perceptual factors (e.g., stimulus size) seem to affect the early ERP component
      but not the affective modulation of the LPP. Although early and late ERP
      components vary with stimulus relevance, given that they are differentially
      affected by stimulus and task manipulations, they appear to index different
      facets of picture processing.

PMID- 17015075
TI  - Dynamics of emotional effects on spatial attention in the human visual cortex.
AB  - An efficient detection of threat is crucial for survival and requires an
      appropriate allocation of attentional resources toward the location of potential
      danger. Recent neuroimaging studies have begun to uncover the brain machinery
      underlying the reflexive prioritization of spatial attention to locations of
      threat-related stimuli. Here, we review functional brain imaging experiments
      using event-related potentials (ERPs) and functional magnetic resonance imaging
      (fMRI) in a dot-probe paradigm with emotional face cues, in which we investigated
      the spatio-temporal dynamics of attentional orienting to a visual target when the
      latter is preceded by either a fearful or happy face, at the same (valid)
      location or at a different (invalid) location in visual periphery. ERP results
      indicate that fearful faces can bias spatial attention toward threat-related
      location, and enhance the amplitude of the early exogenous visual P1 activity
      generated within the extrastriate cortex in response to a target following a
      valid rather than invalid fearful face. Furthermore, this gain control mechanism
      in extrastriate cortex (at 130-150 ms) is preceded by an earlier modulation of
      activity in posterior parietal regions (at 40-80 ms) that may provide a critical
      source of top-down signals on visual cortex. Happy faces produced no modulation
      of ERPs in extrastriate and parietal cortex. fMRI data also show increased
      responses in the occipital visual cortex for valid relative to invalid targets
      following fearful faces, but in addition reveal significant decreases in
      intraparietal cortex and increases in orbitofrontal cortex when targets are
      preceded by an invalid fearful face, suggesting that negative emotional stimuli
      may not only draw but also hold spatial attention more strongly than neutral or
      positive stimuli. These data confirm that threat may act as a powerful exogenous
      cue and trigger reflexive shifts in spatial attention toward its location,
      through a rapid temporal sequence of neural events in parietal and temporo
      occipital areas, with dissociable neural substrates for engagement benefits in
      attention affecting activity in extrastriate occipital areas and increased
      disengagement costs affecting intraparietal cortex. These brain-imaging results
      reveal how emotional signals related to threat can play an important role in
      modulating spatial attention to afford flexible perception and action.

PMID- 17015076
TI  - The neural basis of narrative imagery: emotion and action.
AB  - It has been proposed that narrative emotional imagery activates an associative
      network of stimulus, semantic, and response (procedural) information. In previous
      research, predicted response components have been demonstrated through
      psychophysiological methods in peripheral nervous system. Here we investigate
      central nervous system concomitants of pleasant, neutral, and unpleasant
      narrative imagery with functional magnetic resonance imaging. Subjects were
      presented with brief narrative scripts over headphones, and then imagined
      themselves engaged in the described events. During script perception, auditory
      association cortex showed enhanced activation during affectively arousing
      (pleasant and unpleasant), relative to neutral imagery. Structures involved in
      language processing (left middle frontal gyrus) and spatial navigation
      (retrosplenium) were also active during script presentation. At the onset of
      narrative imagery, supplementary motor area, lateral cerebellum, and left
      inferior frontal gyrus were initiated, showing enhanced signal change during
      affectively arousing (pleasant and unpleasant), relative to neutral scripts.
      These data are consistent with a bioinformational model of emotion that considers
      response mobilization as the measurable output of narrative imagery.

PMID- 17015077
TI  - Subliminal emotion perception in brain imaging: findings, issues, and
      recommendations.
AB  - Many theories of emotion propose that emotional input is processed preferentially
      due to its relevance for the organism. Further, because consciousness has limited
      capacity, these considerations imply that emotional input ought to be processed
      even if participants are perceptually unaware of the input (subliminal
      perception). Although brain imaging has studied effects of unattended, suppressed
      (in binocular rivalry), and visually masked emotional pictures, conclusions
      regarding subliminal perception have been mixed. The reason is that subliminal
      perception demands a concept of an awareness threshold or limen, but there is no
      agreement on how to define and measure this threshold. Although different
      threshold concepts can be identified in psychophysics (signal detection theory),
      none maps directly onto perceptual awareness. Whereas it may be tempting to
      equate unawareness with the complete absence of objective discrimination ability
      (d'=0), this approach is incompatible with lessons from blindsight and denies the
      subjective nature of consciousness. This review argues that perceptual awareness
      is better viewed as a continuum of sensory states than a binary state. When
      levels of awareness are characterized carefully in terms of objective
      discrimination and subjective experience, findings can be informative regarding
      the relative independence of effects from awareness and the potentially
      moderating role of awareness in processing emotional input. Thus, because the
      issue of a threshold concept may never be resolved completely, the emphasis is to
      not prove subliminal perception but to compare effects at various levels of
      awareness.

PMID- 17015078
TI  - Neuroimaging methods in affective neuroscience: selected methodological issues.
AB  - A current goal of affective neuroscience is to reveal the relationship between
      emotion and dynamic brain activity in specific neural circuits. In humans,
      noninvasive neuroimaging measures are of primary interest in this endeavor.
      However, methodological issues, unique to each neuroimaging method, have
      important implications for the design of studies, interpretation of findings, and
      comparison across studies. With regard to event-related brain potentials, we
      discuss the need for dense sensor arrays to achieve reference-independent
      characterization of field potentials and improved estimate of cortical brain
      sources. Furthermore, limitations and caveats regarding sparse sensor sampling
      are discussed. With regard to event-related magnetic field (ERF) recordings, we
      outline a method to achieve magnetoencephalography (MEG) sensor standardization,
      which improves effects' sizes in typical neuroscientific investigations, avoids
      the finding of ghost effects, and facilitates comparison of MEG waveforms across
      studies. Focusing on functional magnetic resonance imaging (fMRI), we question
      the unjustified application of proportional global signal scaling in emotion
      research, which can greatly distort statistical findings in key structures
      implicated in emotional processing and possibly contributing to conflicting
      results in affective neuroscience fMRI studies, in particular with respect to
      limbic and paralimbic structures. Finally, a distributed EEG/MEG source analysis
      with statistical parametric mapping is outlined providing a common software
      platform for hemodynamic and electromagnetic neuroimaging measures. Taken
      together, to achieve consistent and replicable patterns of the relationship
      between emotion and neuroimaging measures, methodological aspects associated with
      the various neuroimaging techniques may be of similar importance as the
      definition of emotional cues and task context used to study emotion.

PMID- 17015079
TI  - Emotional and semantic networks in visual word processing: insights from ERP
      studies.
AB  - The event-related brain potential (ERP) literature concerning the impact of
      emotional content on visual word processing is reviewed and related to general
      knowledge on semantics in word processing: emotional connotation can enhance
      cortical responses at all stages of visual word processing following the assembly
      of visual word form (up to 200 ms), such as semantic access (around 200 ms),
      allocation of attentional resources (around 300 ms), contextual analysis (around
      400 ms), and sustained processing and memory encoding (around 500 ms). Even
      earlier effects have occasionally been reported with subliminal or perceptual
      threshold presentation, particularly in clinical populations. Here, the
      underlying mechanisms are likely to diverge from the ones operational in standard
      natural reading. The variability in timing of the effects can be accounted for by
      dynamically changing lexical representations that can be activated as required by
      the subjects' motivational state, the task at hand, and additional contextual
      factors. Throughout, subcortical structures such as the amygdala are likely to
      contribute these enhancements. Further research will establish whether or when
      emotional arousal, valence, or additional emotional properties drive the observed
      effects and how experimental factors interact with these. Meticulous control of
      other word properties known to affect ERPs in visual word processing, such as
      word class, length, frequency, and concreteness and the use of more standardized
      EEG procedures is vital. Mapping the interplay between cortical and subcortical
      mechanisms that give rise to amplified cortical responses to emotional words will
      be of highest priority for future research.

PMID- 17015080
TI  - Event-related potential studies of language and emotion: words, phrases, and task
      effects.
AB  - This chapter reviews research that focuses on the effects of emotionality of
      single words, and of simple phrases, on event-related brain potentials when these
      are presented visually in various tasks. In these studies, presentation of
      emotionally evocative language material has consistently elicited a late (c. 300
      600 ms post-onset) positive-going, largely frontal-central shift in the event
      related potentials (ERPs), relative to neutral materials. Overall, affectively
      pleasant and unpleasant words or phrases are quite similar in their neuroelectric
      profiles and rarely differ substantively. This emotionality effect is enhanced in
      both amplitude and latency when emotional content is task relevant, but is also
      reliably observed when the task involves other semantically engaging tasks. On
      the other hand, it can be attenuated or eliminated when the task does not involve
      semantic evaluation (e.g., lexical decisions to words or orthographic judgments
      to the spelling patterns) or when comprehension of phrases requires integration
      of the connotative meaning of several words (e.g., compare dead puppy and dead
      tyrant). Taken together, these studies suggest that the emotionality of written
      language has a rapid and robust impact on ERPs, which can be modulated by
      specific task demands as well as the linguistic context in which the affective
      stimulus occurs.

PMID- 17015081
TI  - Emotional connotation of words: role of emotion in distributed semantic systems.
AB  - One current doctrine regarding lexical-semantic functions asserts separate input
      and output lexicons with access to a central semantic core. In other words,
      processes related to word form have separate representations for input
      (comprehension) vs. output (expression), while processes related to meaning are
      not split along the input-output dimension. Recent evidence from our laboratory
      suggests that semantic processes related to emotional connotation may be an
      exception to this rule. The ability to distinguish among different emotional
      connotations may be linked distinctly both to attention systems that select
      specific sensory input for further processing and to intention systems that
      select specific actions for output. In particular, the neuroanatomic substrates
      for emotional connotation on the input side of the equation appear to differ from
      the substrates on the output side of the equation. Implications for semantic
      processing of emotional connotation and its relationship to attention and
      motivation systems are discussed.

PMID- 17015082
TI  - Macroscopic brain dynamics during verbal and pictorial processing of affective
      stimuli.
AB  - Emotions can be viewed as action dispositions, preparing an individual to act
      efficiently and successfully in situations of behavioral relevance. To initiate
      optimized behavior, it is essential to accurately process the perceptual elements
      indicative of emotional relevance. The present chapter discusses effects of
      affective content on neural and behavioral parameters of perception, across
      different information channels. Electrocortical data are presented from studies
      examining affective perception with pictures and words in different task
      contexts. As a main result, these data suggest that sensory facilitation has an
      important role in affective processing. Affective pictures appear to facilitate
      perception as a function of emotional arousal at multiple levels of visual
      analysis. If the discrimination between affectively arousing vs. nonarousing
      content relies on fine-grained differences, amplification of the cortical
      representation may occur as early as 60-90 ms after stimulus onset. Affectively
      arousing information as conveyed via visual verbal channels was not subject to
      such very early enhancement. However, electrocortical indices of lexical access
      and/or activation of semantic networks showed that affectively arousing content
      may enhance the formation of semantic representations during word encoding. It
      can be concluded that affective arousal is associated with activation of
      widespread networks, which act to optimize sensory processing. On the basis of
      prioritized sensory analysis for affectively relevant stimuli, subsequent steps
      such as working memory, motor preparation, and action may be adjusted to meet the
      adaptive requirements of the situation perceived.

PMID- 17015083
TI  - Intonation as an interface between language and affect.
AB  - The vocal expression of human emotions is embedded within language and the study
      of intonation has to take into account two interacting levels of information-
      emotional and semantic meaning. In addition to the discussion of this dual coding
      system, an extension of Brunswik's lens model is proposed. This model includes
      the influences of conventions, norms, and display rules (pull effects) and
      psychobiological mechanisms (push effects) on emotional vocalizations produced by
      the speaker (encoding) and the reciprocal influences of these two aspects on
      attributions made by the listener (decoding), allowing the dissociation and
      systematic study of the production and perception of intonation. Three empirical
      studies are described as examples of possibilities of dissociating these
      different phenomena at the behavioral and neurological levels in the study of
      intonation.

PMID- 17015084
TI  - Cerebral processing of linguistic and emotional prosody: fMRI studies.
AB  - During acoustic communication in humans, information about a speaker's emotional
      state is predominantly conveyed by modulation of the tone of voice (emotional or
      affective prosody). Based on lesion data, a right hemisphere superiority for
      cerebral processing of emotional prosody has been assumed. However, the available
      clinical studies do not yet provide a coherent picture with respect to
      interhemispheric lateralization effects of prosody recognition and
      intrahemispheric localization of the respective brain regions. To further
      delineate the cerebral network engaged in the perception of emotional tone, a
      series of experiments was carried out based upon functional magnetic resonance
      imaging (fMRI). The findings obtained from these investigations allow for the
      separation of three successive processing stages during recognition of emotional
      prosody: (1) extraction of suprasegmental acoustic information predominantly
      subserved by right-sided primary and higher order acoustic regions; (2)
      representation of meaningful suprasegmental acoustic sequences within posterior
      aspects of the right superior temporal sulcus; (3) explicit evaluation of
      emotional prosody at the level of the bilateral inferior frontal cortex.
      Moreover, implicit processing of affective intonation seems to be bound to
      subcortical regions mediating automatic induction of specific emotional reactions
      such as activation of the amygdala in response to fearful stimuli. As concerns
      lower level processing of the underlying suprasegmental acoustic cues, linguistic
      and emotional prosody seem to share the same right hemisphere neural resources.
      Explicit judgment of linguistic aspects of speech prosody, however, appears to be
      linked to left-sided language areas whereas bilateral orbitofrontal cortex has
      been found involved in explicit evaluation of emotional prosody. These
      differences in hemispheric lateralization effects might explain that specific
      impairments in nonverbal emotional communication subsequent to focal brain
      lesions are relatively rare clinical observations as compared to the more
      frequent aphasic disorders.

PMID- 17015085
TI  - Affective and linguistic processing of speech prosody: DC potential studies.
AB  - Speech melody or prosody subserves linguistic, emotional, and pragmatic functions
      in speech communication. Prosodic perception is based on the decoding of acoustic
      cues with a predominant function of frequency-related information perceived as
      speaker's pitch. Evaluation of prosodic meaning is a cognitive function
      implemented in cortical and subcortical networks that generate continuously
      updated affective or linguistic speaker impressions. Various brain-imaging
      methods allow delineation of neural structures involved in prosody processing. In
      contrast to functional magnetic resonance imaging techniques, DC (direct current,
      slow) components of the EEG directly measure cortical activation without temporal
      delay. Activation patterns obtained with this method are highly task specific and
      intraindividually reproducible. Studies presented here investigated the
      topography of prosodic stimulus processing in dependence on acoustic stimulus
      structure and linguistic or affective task demands, respectively. Data obtained
      from measuring DC potentials demonstrated that the right hemisphere has a
      predominant role in processing emotions from the tone of voice, irrespective of
      emotional valence. However, right hemisphere involvement is modulated by diverse
      speech and language-related conditions that are associated with a left hemisphere
      participation in prosody processing. The degree of left hemisphere involvement
      depends on several factors such as (i) articulatory demands on the perceiver of
      prosody (possibly, also the poser), (ii) a relative left hemisphere
      specialization in processing temporal cues mediating prosodic meaning, and (iii)
      the propensity of prosody to act on the segment level in order to modulate word
      or sentence meaning. The specific role of top-down effects in terms of either
      linguistically or affectively oriented attention on lateralization of stimulus
      processing is not clear and requires further investigations.

PMID- 17015086
TI  - Lateralization of emotional prosody in the brain: an overview and synopsis on the
      impact of study design.
AB  - Recently, research on the lateralization of linguistic and nonlinguistic
      (emotional) prosody has experienced a revival. However, both neuroimaging and
      patient evidence do not draw a coherent picture substantiating right-hemispheric
      lateralization of prosody and emotional prosody in particular. The current
      overview summarizes positions and data on the lateralization of emotion and
      emotional prosodic processing in the brain and proposes that: (1) the realization
      of emotional prosodic processing in the brain is based on differentially
      lateralized subprocesses and (2) methodological factors can influence the
      lateralization of emotional prosody in neuroimaging investigations. Latter
      evidence reveals that emotional valence effects are strongly right lateralized in
      studies using compact blocked presentation of emotional stimuli. In contrast,
      data obtained from event-related studies are indicative of bilateral or left
      accented lateralization of emotional prosodic valence. These findings suggest a
      strong interaction between language and emotional prosodic processing.

PMID- 17015087
TI  - Psychoacoustic studies on the processing of vocal interjections: how to
      disentangle lexical and prosodic information?
AB  - Both intonation (affective prosody) and lexical meaning of verbal utterances
      participate in the vocal expression of a speaker's emotional state, an important
      aspect of human communication. However, it is still a matter of debate how the
      information of these two 'channels' is integrated during speech perception. In
      order to further analyze the impact of affective prosody on lexical access, so
      called interjections, i.e., short verbal emotional utterances, were investigated.
      The results of a series of psychoacoustic studies indicate the processing of
      emotional interjections to be mediated by a divided cognitive mechanism
      encompassing both lexical access and the encoding of prosodic data. Emotional
      interjections could be separated into elements with high- or low-lexical content.
      As concerns the former items, both prosodic and propositional cues have a
      significant influence upon recognition rates, whereas the processing of the low
      lexical cognates rather solely depends upon prosodic information. Incongruencies
      between lexical and prosodic data structures compromise stimulus identification.
      Thus, the analysis of utterances characterized by a dissociation of the prosodic
      and lexical dimension revealed prosody to exert a stronger impact upon listeners'
      judgments than lexicality. Taken together, these findings indicate that both
      propositional and prosodic speech components closely interact during speech
      perception.

PMID- 17015088
TI  - Judging emotion and attitudes from prosody following brain damage.
AB  - Research has long indicated a role for the right hemisphere in the decoding of
      basic emotions from speech prosody, although there are few data on how the right
      hemisphere is implicated in processes for understanding the emotive "attitudes"
      of a speaker from prosody. We describe recent clinical studies that compared how
      well listeners with and without focal right hemisphere damage (RHD) understand
      speaker attitudes such as "confidence" or "politeness," which are signaled in
      large part by prosodic features of an utterance. We found that RHD listeners as a
      group were abnormally sensitive to both the expressed confidence and expressed
      politeness of speakers, and that these difficulties often correlated with
      impairments for understanding basic emotions from prosody in many RHD
      individuals. Our data emphasize a central role for the right hemisphere in the
      ability to appreciate emotions and speaker attitudes from prosody, although the
      precise source of these social-pragmatic deficits may arise in different ways in
      the context of right hemisphere compromise.

PMID- 17015089
TI  - Processing of facial identity and expression: a psychophysical, physiological,
      and computational perspective.
AB  - A deeper understanding of how the brain processes visual information can be
      obtained by comparing results from complementary fields such as psychophysics,
      physiology, and computer science. In this chapter, empirical findings are
      reviewed with regard to the proposed mechanisms and representations for
      processing identity and emotion in faces. Results from psychophysics clearly show
      that faces are processed by analyzing component information (eyes, nose, mouth,
      etc.) and their spatial relationship (configural information). Results from
      neuroscience indicate separate neural systems for recognition of identity and
      facial expression. Computer science offers a deeper understanding of the required
      algorithms and representations, and provides computational modeling of
      psychological and physiological accounts. An interdisciplinary approach taking
      these different perspectives into account provides a promising basis for better
      understanding and modeling of how the human brain processes visual information
      for recognition of identity and emotion in faces.

PMID- 17015090
TI  - Investigating audiovisual integration of emotional signals in the human brain.
AB  - Humans can communicate their emotional state via facial expression and affective
      prosody. This chapter reviews behavioural, neuroanatomical, electrophysiological
      and neuroimaging studies pertaining to audiovisual integration of emotional
      communicative signals. Particular emphasis will be given to neuroimaging studies
      using positron emission tomography (PET) or functional magnetic resonance imaging
      (fMRI). Conjunction analyses, interaction analyses, correlation analyses between
      haemodynamic responses and behavioural effects and connectivity analyses have
      been employed to analyse neuroimaging data. There is no general agreement as to
      which of these approaches can be considered "optimal" to classify brain regions
      as multisensory. We argue that these approaches provide complementing information
      as they assess different aspects of multisensory integration of emotional
      information. Assets and drawbacks of the different analysis types are discussed
      and demonstrated on the basis of one fMRI data set.

PMID- 17015091
TI  - Role of the amygdala in processing visual social stimuli.
AB  - We review the evidence implicating the amygdala as a critical component of a
      neural network of social cognition, drawing especially on research involving the
      processing of faces and other visual social stimuli. We argue that, although it
      is clear that social behavioral representations are not stored in the amygdala,
      the most parsimonious interpretation of the data is that the amygdala plays a
      role in guiding social behaviors on the basis of socioenvironmental context.
      Thus, it appears to be required for normal social cognition. We propose that the
      amygdala plays this role by attentionally modulating several areas of visual and
      somatosensory cortex that have been implicated in social cognition, and in
      helping to direct overt visuospatial attention in face gaze. We also hypothesize
      that the amygdala exerts attentional modulation of simulation in somatosensory
      cortices such as supramarginal gyrus and insula. Finally, we argue that the term
      emotion be broadened to include increased attention to bodily responses and their
      representation in cortex.

PMID- 17015092
TI  - Towards a unifying neural theory of social cognition.
AB  - Humans can effortlessly understand a lot of what is going on in other peoples'
      minds. Understanding the neural basis of this capacity has proven quite
      difficult. Since the discovery of mirror neurons, a number of successful
      experiments have approached the question of how we understand the actions of
      others from the perspective of sharing their actions. Recently we have
      demonstrated that a similar logic may apply to understanding the emotions and
      sensations of others. Here, we therefore review evidence that a single mechanism
      (shared circuits) applies to actions, sensations and emotions: witnessing the
      actions, sensations and emotions of other individuals activates brain areas
      normally involved in performing the same actions and feeling the same sensations
      and emotions. We propose that these circuits, shared between the first (I do, I
      feel) and third person perspective (seeing her do, seeing her feel) translate the
      vision and sound of what other people do and feel into the language of the
      observers own actions and feelings. This translation could help understand the
      actions and feelings of others by providing intuitive insights into their inner
      life. We propose a mechanism for the development of shared circuits on the basis
      of Hebbian learning, and underline that shared circuits could integrate with more
      cognitive functions during social cognitions.

PMID- 17015093
TI  - Empathizing: neurocognitive developmental mechanisms and individual differences.
AB  - This chapter reviews the Mindreading System model encompassing four
      neurocognitive mechanisms (ID, EDD, SAM, and ToMM) before reviewing the revised
      empathizing model encompassing two new neurocognitive mechanisms (TED and TESS).
      It is argued that the empathizing model is more comprehensive because it entails
      perception, interpretation, and affective responses to other agents. Sex
      differences in empathy (female advantage) are then reviewed, as a clear example
      of individual differences in empathy. This leads into an illustration of
      individual differences using the Empathy Quotient (EQ). Finally, the neuroimaging
      literature in relation to each of the neurocognitive mechanisms is briefly
      summarized and a new study is described that tests if different brain regions
      respond to the perception of different facial expressions of emotion, as a
      function of the observer's EQ.

PMID- 17015094
TI  - The multiple facets of empathy: a survey of theory and evidence.
AB  - Empathy is the ability to perceive and understand other people's emotions and to
      react appropriately. This ability is a necessary prerequisite for successful
      interpersonal interaction. Empathy is a multifaceted construct including low
      level mechanisms like emotional contagion as well as high-level processes like
      perspective-taking. The ability to empathize varies between individuals and is
      considered a stable personality trait: some people are generally more successful
      in empathizing than others. In this chapter we will first present different
      conceptualizations of the construct of empathy, and refer to empathy-regulating
      processes as well as to the relationship between empathy and social behavior.
      Then, we will review peripheral physiological and brain imaging studies
      pertaining to low- and high-level empathic processes, empathy-modulating
      processes, and the link between empathy and social behavior. Further, we will
      present evidence regarding interindividual differences in these processes as an
      important source of information for solving the conundrum of how the
      comprehension of others' emotions is achieved by our brains.

PMID- 17015095
TI  - Partly dissociable neural substrates for recognizing basic emotions: a critical
      review.
AB  - Facial expressions are powerful non-verbal displays of emotion which signal
      valence information to others and constitute an important communicative element
      in social interaction. Six basic emotional expressions (fear, disgust, anger,
      surprise, happiness, and sadness) have been shown to be universal in their
      performance and perception. Recently, a growing number of clinical and functional
      imaging studies have aimed at identifying partly dissociable neural subsystems
      for recognizing basic emotions. Convincing results have been obtained for fearful
      and disgusted facial expressions only. Empirical evidence for a specialized
      neural representation of anger, surprise, sadness, or happiness is more limited,
      primarily due to lack of clinical cases with selective impairments in recognizing
      these emotions. In functional imaging research, the detection of dissociable
      neural responses requires direct comparisons of signal changes associated with
      the perception of different emotions, which are often not provided. Only recently
      has evidence been obtained that the recruitment of emotion-specific neural
      subsystems may be closely linked to characteristic facial features of single
      expressions such as the eye region for fearful faces. Investigations into the
      neural systems underlying the processing of such diagnostic cues for each of the
      six basic emotions may be helpful to further elucidate their neural
      representation.

PMID- 17015096
TI  - Integration of emotion and cognition in patients with psychopathy.
AB  - Psychopathy is a personality disorder associated with emotional characteristics
      like impulsivity, manipulativeness, affective shallowness, and absence of remorse
      or empathy. The impaired emotional responsiveness is considered to be the
      hallmark of the disorder. There are two theories that attempt to explain the
      emotional dysfunction and the poor socialization in psychopathy: (1) the low-fear
      model and (2) the inhibition of violence model. Both approaches are supported by
      several studies. Studies using aversive conditioning or the startle modulation
      underline the severe difficulties in processing negative stimuli in psychopaths.
      Studies that explore the processing of emotional expressions show a deficit of
      psychopathic individuals for processing sad or fearful facial expressions or
      vocal affect. In the cognitive domain, psychopaths show performance deficits in
      the interpretation of the motivational significance of stimuli. Studies
      investigating the impact of emotions on cognitive processes show that in
      psychopaths in contrast to healthy controls negative emotions drain no resources
      from a cognitive task. It is suggested that dysfunctions in the frontal cortex,
      especially the orbitofrontal cortex, the cingulate cortex and the amygdala are
      associated with the emotional and cognitive impairments.

PMID- 17015097
TI  - Disordered emotional processing in schizophrenia and one-sided brain damage.
AB  - The work concentrates on the problem of human emotions in healthy and
      pathologically changed brains, mainly in persons afflicted with schizophrenia or
      with organic impairments localized in one of the cerebral hemispheres. This
      chapter presents the state of current knowledge concerning the hemispheric
      lateralization of emotions among healthy people, psychiatric patients, and
      patients with one-sided brain lesion, on the basis of clinical observations, the
      results of experimental work, and the newest neuroimaging techniques. The
      numerous experiments and scientific methods used to assess the hemispheric
      lateralization of emotions and the discrepancies in their results point toward a
      lack of consistent theory in the field of hemispheric specialization in the
      regulation of emotional processes. Particular scientific interest was taken in
      the emotions of persons afflicted with schizophrenia, either in its early or late
      stages. This was inspired by the emotional behavior of schizophrenic patients on
      a psychiatric ward and their ability to perceive and express emotions during
      various stages of the schizophrenic process. In order to examine the cerebral
      manifestations of emotional deficits and the specialization of cerebral
      hemispheres for emotional processes, the author has described the emotional
      behavior of patients with unilateral cerebral stroke, i.e., patients with damage
      to the right or left cerebral hemisphere. Overall, the inferior performance of
      emotional tasks by right-hemisphere-damaged patients compared to other groups
      might support right-hemisphere superiority for affect perception despite
      variations in the stimuli used.

PMID- 17015098
TI  - The biochemistry of dysfunctional emotions: proton MR spectroscopic findings in
      major depressive disorder.
AB  - Key neural systems involved in the processing and communication of emotions are
      impaired in patients with major depressive disorder (MDD). Emotional and
      behavioral symptoms are thought to be caused by damage or dysfunction in specific
      areas of the brain that are responsible for directing attention, motivating
      behavior, and learning the significance of environmental stimuli. Functional
      brain studies with positron emission tomography (PET) and functional magnetic
      resonance imaging (fMRI) give support for functional abnormalities in MDD that
      are predominantly located in areas known to play an important role in the
      communication and processing of emotions. Disturbances in emotional processing as
      they are observed in MDD, if any, have very subtle morphometrical brain
      correlates. With proton magnetic resonance spectroscopy (1H MRS), brain
      metabolites can be measured noninvasively in vivo, thus furthering the
      understanding of the effects of changes in neurotransmitters within the brain.
      The current literature on 1H MRS studies in MDD is small with a large diversity
      of MRS methods applied, brain regions studied, and metabolite changes found.
      Nevertheless, there is strong evidence that changes in neurometabolite
      concentrations in MDD occur within brain regions, which are involved in the
      processing and communication of emotions that can be monitored by 1H MRS. This
      review summarizes the literature about biochemical changes quantified via 1H MRS
      in MDD patients in brain regions that play an important role for the
      communication and processing of emotions.

PMID- 17015102
TI  - What's holding us back? Understanding barriers to innovation in academic
      neurosurgery.

PMID- 17015103
TI  - Impact of radiosurgery on the surgical treatment of trigeminal neuralgia.
AB  - BACKGROUND: The history of the development of current available techniques to
      treat TN was reviewed. METHODS: The largest peer-reviewed publications on the
      surgical treatment of refractory TN were analyzed, considering the pros and cons
      of each technique. Results of modern peer-reviewed radiosurgery series were
      presented, taking into consideration the approach of each research article.
      Radiation doses and targets for radiosurgery were discussed to maximize the
      understanding of this technique. RESULTS: It is concluded that radiosurgery is
      the least invasive modality with the fewest side effects, although, to match the
      results of the competing techniques, a substantial number of patients still need
      some medication intake. CONCLUSION: Further studies determining the ideal target
      and radiation dose may bring radiosurgery results to the level of the ones
      achieved with microvascular decompression, currently considered the gold-standard
      method.

PMID- 17015104
TI  - Is every chronic low back pain benign? Case report.
AB  - BACKGROUND: There is a well-recognized association between chronic back pain and
      the existence of an AAA. In literature, there are few reported AAA cases that
      describe patients with extensive pressure erosion of the vertebral body. CASE
      DESCRIPTION: The authors present the case of a 38-year-old woman with chronic low
      back pain for the last 2 years in whom an AAA was formed during the follow-up
      period. The patient presented with an episode of low back pain following hard
      work 2 years ago. MR imaging of the lumbar spine was reported as disc
      degeneration at the L4-5 and L5-S1 levels. She was given medical treatment and
      was doing well with occasional back pain for a year. One year later, she suffered
      another disabling pain attack, and MR imaging revealed an additional focal disc
      protrusion at the L4-5 level. She was again medically treated. In August 2004,
      she presented with severe low back pain, and this time, MR imaging showed edema
      and erosion at the anterior part of L3 vertebra body. MR imaging studies (2- and
      3-dimensional) depicted AAA as the cause. She was operated on, and the aneurysm
      was resected with graft repair of the site. She was pain-free in the
      postoperative period. CONCLUSIONS: The evaluation of a patient with chronic back
      pain needs a thorough clinical and radiological workup. Limited evaluation of the
      bony and nervous structures of the spinal canal radiologically is insufficient.
      Pre- and paravertebral structures as well as vertebral body should carefully be
      evaluated to diagnose other causes of pain.

PMID- 17015107
TI  - Anterior odontoid fixation using a 4.5-mm Herbert screw: The first report of 20
      consecutive cases with odontoid fracture.
AB  - BACKGROUND: Anterior screw fixation provides the best anatomical and functional
      results for odontoid process fracture (type II and "shallow" type III) with
      intact transverse ligament. The purpose of this study is to evaluate the clinical
      results of the 4.5-mm-diameter cannulated Herbert screw in the anterior odontoid
      fixation. METHODS: From May 2003 to November 2005, 20 consecutive cases of types
      II and III odontoid process fractures were treated with anterior screw fixation
      using a 4.5-mm Herbert screw. The Herbert screw has double threads, with
      different pitches on the distal and proximal ends. It has no head, so it can be
      inserted through articular cartilage and buried below bone surface. RESULTS:
      There were 16 male and 4 female patients whose ages ranged from 15 to 76 years
      (mean, 43.7 years). The fracture type was type II-A in 4 patients, II-N in 9
      patients, II-P in 5 patients, and III in 2 patients. The range of follow-up was 3
      to 36 months (mean, 18.6 months). There were an overall bone fusion rate in 17
      cases (85%), fibrous union in 1 (5%), and nonunion in 2 (10%). Overall,
      complication unrelated to hardware occurred in the one (postoperative dysphagia)
      without complication-related hardware failure. CONCLUSIONS: The Herbert screw is
      very useful in anterior fixation for types II and III odontoid process fractures.
      This series showed successful clinical results comparable with that of the 3.5-mm
      cannulated cancellous screw and distinct advantages over conventional screws in
      the aspect of biomechanical properties and less invasiveness.

PMID- 17015109
TI  - The polymethyl methacrylate cervical cage for treatment of cervical disk disease
      Part III. Biomechanical properties.
AB  - BACKGROUND: In a previous article, we used the PMMA cervical cage in the
      treatment of single-level cervical disk disease and the preliminary clinical
      results were satisfactory. However, the mechanical properties of the PMMA cage
      were not clear. Therefore, we designed a comparative in vitro biomechanical study
      to determine the mechanical properties of the PMMA cage. METHODS: The PMMA
      cervical cage and the Solis PEEK cervical cage were compressed in a materials
      testing machine to determine the mechanical properties. RESULTS: The compressive
      yield strength of the PMMA cage (7030 +/- 637 N) was less than that of the Solis
      polymer cervical cage (8100 +/- 572 N). The ultimate compressive strength of the
      PMMA cage (8160 +/- 724 N) was less than that of the Solis cage (9100 +/- 634 N).
      The stiffness of the PMMA cervical cage (8106 +/- 817 N/mm) was greater than that
      of the Solis cage (6486 +/- 530 N/mm). The elastic modulus of the PMMA cage (623
      +/- 57 MPa) was greater than that of the Solis cage (510 +/- 42 MPa). The
      elongation of PMMA cage (43.5 +/- 5.7%) was larger than that of the Solis cage
      (36.1 +/- 4.3%). CONCLUSIONS: Although the compressive yield strength and
      ultimate compressive strength of the PMMA cervical cage were less than those of
      the Solis polymer cage, the mechanical properties are better than those of the
      cervical vertebral body. The PMMA cage is strong and safe for use as a spacer for
      cervical interbody fusion. Compared with other cage materials, the PMMA cage has
      many advantages and no obvious failings at present. However, the PMMA cervical
      cage warrants further long-term clinical study.

PMID- 17015111
TI  - BioGlue for prevention of postoperative cerebrospinal fluid leaks in
      transsphenoidal surgery: A case series.
AB  - BACKGROUND: The efficacy of BioGlue (CryoLife, Inc, Atlanta, Ga) surgical
      adhesive in transsphenoidal surgery was assessed as an adjunct in the prevention
      of postoperative CSF leaks. METHODS: All patients in whom BioGlue was used for an
      intraoperative skull base reconstruction were retrospectively identified.
      Intraoperative CSF leaks were graded according to size (grade 1, small weeping
      leak without obvious diaphragmatic defect; grade 2, moderate leak with a definite
      diaphragmatic defect; grade 3, large diaphragmatic and/or dural defect). CSF leak
      repair was tailored to CSF leak grade. BioGlue was applied as a reinforcement
      over collagen sponge as the last layer of the repair. RESULTS: Over 28 months, a
      total of 282 patients underwent endonasal surgery. Of these patients, 124 (79
      women; age range, 8-84 years), in 128 procedures, had an intraoperative CSF leak
      repair reinforced with BioGlue. Pathology included 80 pituitary adenomas, 11
      craniopharyngiomas, 7 Rathke's cleft cysts, 6 chordomas, 5 meningiomas, 4
      spontaneous CSF leaks, 3 arachnoid cysts, and 8 other parasellar pathologies.
      There were 62 (48.4%) grade 1, 41 (32.0%) grade 2, and 25 (19.5%) grade 3 leak
      repairs. The overall repair failure rate was 1.6% (2 cases), with the failures
      occurring in patients with grade 3 leaks, including 1 who developed meningitis;
      there was no failure of grades 1 and 2 leaks. The 2 failures were attributed
      largely to technical aspects of the repair rather than to failure of BioGlue per
      se. CONCLUSIONS: BioGlue appears to be an effective adjunct in preventing
      postoperative CSF leaks after transsphenoidal surgery. However, careful attention
      to technical details of the repair is still required to prevent failures,
      especially when closing large dural and diaphragmatic defects.

PMID- 17015114
TI  - Different outcomes between two sides after bilateral sympathetic ganglion
      interruption for hyperhidrosis.
AB  - BACKGROUND: Although the determination of the correct ganglion under direct
      vision through thoracoscopy by an experienced surgeon is almost unerring, there
      is still a 4.3% rate of clipping at the unintended level. METHODS: Through the
      review of the most recent patients (N = 117) with various sympathetic disorders
      undergoing thoracoscopic sympathetic interruption over different ganglions by
      clipping, we found that 5 cases were clipped at the unplanned level. The
      immediate manifestations were the different outcomes between both sides of the
      face, trunk, and extremities. The postoperative chest radiographs demonstrated
      the error. RESULTS: All patients received a second operation in which the
      unintended clip was removed, and a new one was applied to the appropriate
      ganglion. The results were satisfactory. CONCLUSIONS: Although the authors in
      this study have the experience of more than 1000 cases of hyperhidrosis, such an
      error is still inevitable. Luckily, by using the clipping method, the error is
      detectable and amendable.

PMID- 17015116
TI  - Principles of neuroanesthesia in aneurysmal subarachnoid hemorrhage: The Helsinki
      experience.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage is a devastating disease that is
      followed by a marked stress response affecting other organs besides the brain.
      The aim in the management of patients with aSAH is not only to prevent
      rebleedings by treating the aneurysm by either microneurosurgery or endovascular
      surgery, but also to evacuate acute space-occupying hematomas and to treat
      hydrocephalus. METHODS: This review is based on the experience of the authors in
      the management of more than 7500 patients with aSAH treated in the Department of
      Neurosurgery at Helsinki University Central Hospital, Finland. RESULTS: The role
      of the neuroanesthesiologist together with the neurosurgeon may begin in the
      emergency department to assess and stabilize the general medical and neurologic
      status of the patients. Early preoperative management of patients in the NICU,
      prevention of rebleeding, and providing a slack brain during microneurosurgical
      procedures are further steps. Postoperative management, prevention, and treatment
      of possible medical complications and cerebrovascular spasm are as necessary as
      high-quality microsurgery. CONCLUSION: Multidisciplinary and professional
      teamwork is essential in the management of patients with cerebral aneurysms.

PMID- 17015118
TI  - Combined direct anastomosis and encephaloduroarteriogaleosynangiosis using
      inverted superficial temporal artery-galeal flap and superficial temporal artery
      galeal pedicle in adult moyamoya disease.
AB  - BACKGROUND: We evaluated the efficacy of combined STA-MCA anastomosis and EDAGS
      using inverted STAGF and STAGP for the treatment of adult MMD. METHODS: This
      study included 8 patients with nonhemorrhagic MMD. There were 6 women and 2 men
      who were between 23 and 62 years old (mean = 37.8 years) in the sample. The
      combined surgery was performed on 12 sides in the 8 patients. The surgical
      results were assessed for clinical outcome, angiographic revascularization, and
      hemodynamic change on HMPAO brain SPECT. The follow-up period ranged from 6 to 62
      months (mean = 27 months). RESULTS: Clinical symptoms and signs were improved or
      stabilized, and the extent of revascularization evident on external carotid
      angiograms was excellent in all 8 patients. The CBF on HMPAO SPECT also improved
      in all 12 sides that were operated on with the combined surgery, except for the
      preexisting infarcted area, on the basal as well as Diamox stimulation studies.
      One patient had a transient speech disturbance after surgery, and another patient
      had delayed wound healing. CONCLUSIONS: The combined STA-MCA anastomosis and
      EDAGS using inverted STAGF/P seems to be one of the most effective surgical
      modalities for the treatment of nonhemorrhagic MMD in adults.

PMID- 17015120
TI  - The endoscopic supraorbital approach to tumors of the middle cranial base.
AB  - BACKGROUND: Access to tumors of the middle cranial base has traditionally
      required wide surgical exposures via open craniotomies. These open techniques
      often require the use of potentially disfiguring skin incisions and are often
      associated with a significant degree of brain retraction and potential morbidity.
      We report our experience with the use of a minimally invasive supraorbital
      endoscopic approach through the eyebrow for excision of middle cranial base
      tumors in 2 cases. METHODS: We describe 2 patients with large-sized middle
      cranial fossa tumors (a medial sphenoid wing meningioma measuring 6 x 4 cm and a
      recurrent right cavernous sinus meningioma measuring 4 x 3.5 cm) that were
      entirely removed via a fully endoscopic supraorbital approach using a 1.5-cm
      keyhole craniotomy. CONCLUSION: These cases demonstrate how the application of
      endoscopic techniques to surgery of the middle cranial base can eliminate the
      need for traditional open techniques without compromising surgical success.

PMID- 17015122
TI  - Successful emergent angioplasty of neurosarcoid vasculitis presenting with
      strokes.
AB  - BACKGROUND: Sarcoidosis is a systemic disease with neurologic involvement in
      approximately 5% of cases. Ischemic events related to neurosarcoid vasculitis are
      rare. We report the successful treatment of symptomatic neurosarcoid vasculitis
      with angioplasty. CASE DESCRIPTION: A 41-year-old African American with a
      diagnosis of neurosarcoid presented with aphasia and right-sided weakness. He was
      treated medically with antiplatelet agents, heparinization, and hypertensive
      therapy. Despite this treatment, he experienced clinical worsening and
      radiographic extension of his infarcts. He underwent successful angioplasty of a
      severe focal stenosis of the left middle cerebral artery. After the procedure, he
      experienced marked improvement in his symptoms and at follow-up continues to
      improve. CONCLUSIONS: We report the angiographic demonstration of
      neurosarcoidosis with large vessel changes and resultant strokes and its
      successful treatment with balloon angioplasty.

PMID- 17015123
TI  - Different modalities of treatment of intracranial mycotic aneurysms: Report of 4
      cases.
AB  - BACKGROUND: Intracranial mycotic aneurysms, although rare neurovascular
      pathology, represented a neurosurgical challenge that required careful stepwise
      decision making. Different approaches for their management were used. We present
      our experience with 4 patients treated in terms of indications and efficacy of
      different treatment modalities. METHODS: Four patients with infective
      endocarditis and 5 intracranial mycotic aneurysms were treated during the last 5
      years. All of the patients were men; their ages ranged between 29 and 62 years
      (mean, 47.3 years). Distal MCA was the commonest site (3 patients) of aneurysm, 1
      was located at the distal PCA, whereas the remaining aneurysm was at the distal
      ACA. Angiographic studies were done in 2 patients because of neurologic signs and
      for screening in 2 patients with documented endocarditis. RESULTS: One patient
      was treated conservatively because of his moribund general condition; 1 patient
      was treated with direct surgical clipping; 1 patient was treated with surgical
      trapping and resection of the aneurysm without revascularization; and the
      remaining patient, harboring 2 distal mycotic aneurysms, was treated with
      selective embolization for his PCA aneurysm and endovascular trapping for the
      distal ACA aneurysm. Follow-up angiographic results showed stable occlusion of
      the aneurysms. No periprocedural technical complications were reported, and none
      of the patients, including the patient with medical treatment only, has ever
      experienced new neurologic events after definitive treatment. CONCLUSIONS:
      Prolonged courses of antibiotics are recommended for all patients with mycotic
      aneurysms. Selective endovascular embolization or trapping with soft and
      ultrasoft electrolytically detachable coils seems to be an effective technique
      that should be considered for treatment of dynamic unruptured mycotic aneurysms,
      with conventional surgical repair restricted for ruptured aneurysms with
      associated hematoma and high intracranial pressure.

PMID- 17015125
TI  - Chronic subdural hematoma in patients with idiopathic thrombocytopenic purpura: A
      case report and review of the literature.
AB  - BACKGROUND: cSDH is a rare form of bleeding in patients with ITP. Intracerebral
      hematoma or subarachnoid hemorrhage is more frequently reported in these
      patients. Spontaneous resolution of cSDH in patients with idiopathic subdural
      hematoma is uncommon. CASE DESCRIPTION: We report a case of spontaneous cSDH in a
      patient with ITP, and we review the related cases in the literature. In our
      patient, the hematoma resolved spontaneously despite very low platelet levels.
      There also was an incidental left parietal convexity meningioma. A review of the
      literature is presented, and the management of the patients is discussed.
      CONCLUSION: In patients with ITP, cSDHs may resolve spontaneously or with medical
      treatment, and surgery might be deferred except in emergency conditions or in
      patients with normal neurological findings. Close neurological and radiological
      observation along with the medical treatment may be appropriate in the management
      of patients with normal neurological findings.

PMID- 17015127
TI  - Unilateral sensorineural hearing loss after spine surgery: Case report and review
      of the literature.
AB  - BACKGROUND: Sudden sensorineural hearing loss is infrequent, with an estimated
      incidence of 5 to 20 cases yearly per 100,000 people. Although multiple
      etiologies have been identified, infection and idiopathic SNHL are most common.
      Sudden sensorineural hearing loss after nonotologic noncardiac surgery is highly
      unusual, particularly after spinal surgery. CASE DESCRIPTION: We report a case of
      unilateral sudden SNHL after lumbar spinal fusion with review of the literature.
      Potential etiologies, treatment, and prognosis are summarized. CONCLUSION:
      Multiple etiologies have been proposed for SNHL after nonotologic noncardiac
      surgery. Excessive positive upper airway pressure during induction of anesthesia
      or Valsalva maneuvers can result in SNHL from LMR. Aberrant NO accumulation in
      the middle ear cavity during general anesthesia with subsequent LMR is also a
      potential etiology, as is excessive leakage of CSF causing a form of
      endolymphatic hydrops. There is no definitive treatment of postoperative SNHL,
      although middle ear exploration may be beneficial for suspected overpressure
      injury to the middle ear, causing a perilymphatic fistula. Corticosteroids have
      been beneficial in certain cases of idiopathic SNHL; however, its effectiveness
      for postoperative SNHL is undocumented.

PMID- 17015129
TI  - Intraoperative dynamic angiography to detect resolution of Bow Hunter's syndrome:
      Technical case report.
AB  - BACKGROUND: Bow Hunter's syndrome is a rare form of vertebrobasilar insufficiency
      that may be successfully treated by surgical intervention. Use of intraoperative
      dynamic transcranial Doppler ultrasound for surgical treatment of vertebrobasilar
      insufficiency has been described in literature. However, this technique was
      inconsistent and unreliable in some patients. We present a case of a patient with
      Bow Hunter's syndrome treated surgically and emphasize the valuable addition of
      intraoperative dynamic angiography to determine resolution of vertebral artery
      compromise. CASE DESCRIPTION: The patient was a 58-year-old man with complaints
      of dizziness, vertigo, and near-syncopal episodes that occurred when he rotated
      his head to the left. Imaging revealed compromise of the dominant left vertebral
      artery with leftward head rotation. An anterior cervical approach with
      decompression of the left subaxial vertebral artery was performed. Significant
      osteophyte formation was observed. Removal of bone and decompression of the
      vertebral artery was performed. Intraoperative dynamic angiography confirmed
      resolution of vertebral artery compression and minimized the amount of
      decompression. No further intervention was required. CONCLUSION: Intraoperative
      dynamic angiography is a definitive test to determine hemodynamic resolution of
      Bow Hunter's syndrome. It offers real-time feedback of vertebral artery
      decompression, potentially minimizes the amount of decompression, and can be
      performed safely.

PMID- 17015131
TI  - Arterial suturing followed by clip reinforcement with circumferential wrapping
      for blister-like aneurysms of the internal carotid artery.
AB  - OBJECTIVE: Blister-like aneurysms of the internal carotid artery (ICA) are very
      fragile, thin-walled aneurysms. These lesions are susceptible to premature
      rupture intraoperatively. We describe two cases of successful arterial suturing
      of these blister-like aneurysms of the ICA, followed by a clip reinforcement
      technique and circumferential wrapping with a silastic sheet. METHODS: Two young
      men presented with a diffuse and dense subarachnoid hemorrhage (SAH) in the basal
      cistern. The initial angiogram obtained soon after the SAH showed a broad-based,
      small bulging appearance of the dorsal wall of the ICA. Intraoperatively, a very
      thin-walled aneurysm was identified on the C2 and C1 segment of the ICA. The
      aneurysms ruptured abruptly during surgical manipulation. After application of
      temporary clips, an aneurysmal tear of the ICA was repaired with 8-0 nylon. To
      prevent the regrowth of the aneurysm, clip reinforcement, by circumferential
      wrapping with a transparent silicone sheet, was added. RESULTS: The postoperative
      clinical course was uneventful, although one patient showed transient right
      hemiparesis due to cerebral vasospasm. Angiographic studies performed
      postoperatively showed complete obliteration of the aneurysm as well as a patent
      ICA lumen in one case and total occlusion of the ICA in the other case. Both
      patients were discharged with no neurological deficits. CONCLUSION: This
      technique can be a useful treatment option for these fragile aneurysms in cases
      where other options, such as direct clips or encircling clips, may be impossible.

PMID- 17015133
TI  - Intraspinal lymphangioma: 2 case reports and literature review.
AB  - BACKGROUND: Lymphangioma of the soft tissue is not uncommon. However, as far as
      the authors know, intraspinal lymphangioma is clinically rare and very few cases
      have been reported previously. METHODS: Two patients who had backache and acratia
      of the lower limbs and difficulty in relieving themselves were examined by plain
      radiography and magnetic resonance imaging before surgery. Treatment consisted of
      the usual technique of surgical resection of the tumor microscopically.
      Histological examination of the resected material confirmed the diagnosis.
      Postoperative follow-up assessment was performed by magnetic resonance imaging.
      RESULTS: Intraspinal lymphangioma is very rare clinically and its cause remains
      controversial. Magnetic resonance imaging can obtain precise position fixing, but
      it is hard to make preoperative qualitative determination. The most effective
      treatment of intraspinal lymphangioma is to excise it totally. CONCLUSIONS: The
      clinical appearance of intraspinal lymphangioma has no character. Magnetic
      resonance imaging is important in diagnosing it. The most effective treatment of
      intraspinal lymphangioma is to excise it totally. Further observation is
      recommended because of the possibility of local recurrence.

PMID- 17015135
TI  - Cortical seeding of a craniopharyngioma after craniotomy: Case report.
AB  - BACKGROUND: Cortical seeding of a craniopharyngioma has been rarely reported. We
      present a case that ectopically recurred along the tract of a previous surgical
      route. METHODS: A 27-year-old woman presented earlier with a suprasellar
      craniopharyngioma. A left frontotemporal craniotomy was done with subtotal
      resection of the tumor because it was strongly adhered to the optic chiasm.
      Histopathology confirmed the diagnosis of craniopharyngioma. Six months after,
      the patient presented with decreased visual acuity and diplopia. She was
      reoperated through the previous craniotomy with a total resection. One year after
      the second surgery, the patient presented with seizures that were difficult to
      control. Magnetic resonance imaging revealed a contrast-enhancing tumor with
      cystic and solid components on the left temporal lobe cortex. The primary tumor
      bed was intact. The patient was reoperated, and the temporal lobe tumor was
      totally removed. Histologic studies showed an adamantinomatous craniopharyngioma.
      The patient was free of neurologic abnormalities, and no new lesion was found in
      the magnetic resonance imaging performed 1 year after the last surgery.
      CONCLUSIONS: Although craniopharyngiomas exhibit a benign histopathologic
      pattern, a total resection combined with careful inspection and irrigation of the
      surgical field is the optimal treatment for preventing local and ectopic
      recurrences. It is strongly recommended that the concerned patients have a long
      term clinical and neuroimaging follow-up.

PMID- 17015137
TI  - Internal carotid artery dorsal wall aneurysm with configurational change: Are
      they all false aneurysms?
AB  - BACKGROUND: Aneurysms arising from nonbranching sites of the ICA, so-called
      dorsal wall aneurysm, are rare entity, and present as blister type or saccular
      type. Occasionally configurational changes have been observed on serial cerebral
      angiography: a small blister-like bulge on ICA wall on initial angiography
      progressing to a saccular appearance within a few weeks. Such aneurysm showing
      configurational change has been regarded as a false aneurysm with fragile wall
      just like blister-type aneurysm, and direct surgical approach has been considered
      highly risky. CASE DESCRIPTION: A 42-year-old woman with a subarachnoid
      hemorrhage revealed small "blister-like" aneurysm at the medial wall of the ICA
      on initial angiography. After 12 days, the following angiograms demonstrated
      increased aneurysmal size and change of shape into a saccular configuration.
      Direct surgical approach was performed. The aneurysm had a relatively firm neck,
      and was successfully clipped without intraoperative rupture. The dome of aneurysm
      was resected after clipping and the histologic examination revealed it as a true
      aneurysm. CONCLUSIONS: This case suggests that all dorsal wall aneurysms with
      configurational change are not false aneurysms, and that angiographic findings do
      not always correlate with the nature of the aneurysmal wall; therefore, we should
      give more credence to direct surgical observation rather than preoperative
      angiographic findings when considering the most suitable surgical option.

PMID- 17015139
TI  - Traumatic pseudoaneurysm of the pharyngeal artery: An unusual cause of
      hematemesis and hematochezia after craniofacial trauma.
AB  - BACKGROUND: Traumatic aneurysms of the internal maxillary artery are extremely
      rare. We report a case of traumatic pseudoaneurysm of the pharyngeal artery, a
      branch of the internal maxillary artery, presenting with hematemesis and
      hematochezia. CASE DESCRIPTION: An 18-year-old man presented with deep drowsy
      consciousness after a motor vehicle accident, in which he had a severe
      craniofacial injury. Three days later, he had hematemesis and hematochezia with a
      marked decrease in circulating hemoglobin level. External carotid arteriography
      performed to rule out vascular injury revealed active leakage from a false
      aneurysm of the pharyngeal artery. The lesion was successfully obliterated by
      superselective endovascular embolization. CONCLUSIONS: In patients with
      craniofacial injury associated with multiple traumas, traumatic pseudoaneurysm of
      the pharyngeal artery should be suspected as one of the possible causes of
      hematemesis and hematochezia. Selective endovascular embolization with cerebral
      angiography is an effective modality for the treatment and diagnosis of this
      lesion.

PMID- 17015142
TI  - The revolution we are living in or why we have trouble changing--"What is holding
      us back?".

PMID- 17015143
TI  - Antiphospholipid antibodies as a possible risk factor for atherosclerosis in
      patients with rheumatoid arthritis.
AB  - Atherosclerosis shares many similarities with inflammatory and autoimmune
      diseases, among them rheumatoid arthritis (RA). Anticardiolipin antibodies (aCL)
      and antibodies against beta2-glycoprotein I (anti-beta2GPI) have been detected in
      sera of RA patients in several studies. We demonstrated aCL and anti-beta2GPI in
      a selected group of 70 patients with RA (premenopausal women, non-diabetic, non
      hypertensive) and compared them with age- and sex-matched controls. There was a
      significant higher internal carotid artery intima-media thickness and number of
      plaques in RA patients compared to controls. aCL of IgG and IgM classes were
      present in 15.7% of RA patients as compared to 5% in the control group. Thirty
      percent of RA patients had anti-beta2GPI of IgG, IgM and IgA classes compared to
      7.5% in controls. Major differences were seen in IgG and IgA classes. Our results
      support the idea that aCL and anti-beta2GPI represent an important risk factor
      for atherosclerosis in RA patients. Elevated levels of phosphatidylserine
      dependent antiprothrombin antibodies did not contribute significantly to the
      general prevalence of antiphospholipid antibodies.

PMID- 17015144
TI  - Identification of a peptide mimicking the binding pattern of an antiphospholipid
      antibody.
AB  - Our objective was to characterize monoclonal antiphospholipid antibodies (APL)
      and identify disease-associated antigens in patients with the antiphospholipid
      syndrome (APS). We used the monoclonal antibody HL-5B, derived from a patient
      with APS suffering from multiple ischemic events, to screen a 12-mer peptide
      phage display library (New England Biolabs, London, England). The identified
      phage clones were sequenced and the derived consensus peptide was synthesized.
      The peptide was used to perform competitive inhibition experiments for their
      ability to inhibit the binding of the monoclonal antibody and of serum antibodies
      to cardiolipin and phosphatidylserine. Additionally patients and control sera
      were screened for their binding reactivities to this peptide. Using this 12-mer
      phage display library the peptide APHKHKASLSIY as consensus peptide for the
      monoclonal antiphospholipid antibody HL-5B could be identified. In competitive
      inhibition studies we showed that this peptide is able to inhibit the binding of
      HL-5B to cardiolipin and phosphatidylserine and furthermore another
      antiphospholipid antibody used as control was also inhibited in its binding to
      phospholipids. Using 21 sera from APS patients 67% showed a binding to the
      peptide in a specific ELISA above the cutoff level, generated with sera from 20
      healthy controls. Out of the reactive patients' sera we used two exemplarily to
      perform inhibition studies. Both sera could be inhibited more than 40% in their
      binding to cardiolipin in a commercially available antiphospholipid antibody
      assay (Aescu.diagnostics, Wendelsheim, Germany). The identified peptide
      APHKHKASLSIY simulates the antigenic structure recognized from a subpopulation of
      serum antiphospholipid antibodies. This might indicate that the diversity of the
      antiphospholipid antibodies is limited and only few epitopes or few common
      structures are responsible for the development of those antibodies. Tests using
      these epitopes will strongly improve laboratory diagnosis of the APS.

PMID- 17015145
TI  - Age-dependent loss of naive T cells in TCR transgenic bone marrow chimeras.
AB  - Study of immune senescence is complicated by low numbers of antigen-specific
      lymphocytes, particularly naive T (Tn)cells which disappear with aging. Although
      T cell receptor (TCR) transgenic mice facilitate aging research, their large
      number of Ag-specific T cells renders their T cell pool abnormal, precluding
      normal in vivo immunity. To create a physiologically relevant model with
      measurable numbers of TCR transgenic CD4+ T cells in the context of normal
      lymphocytes, mixed (DO11.10+BALB/c) bone marrow (BM) chimeras were constructed.
      As found in normal mice, the total number of transgenic T cells and the Tn:memory
      T cell ratio declined with the aging of the BM chimeras. Although these shifts in
      T cell subsets were evident in both the lymph nodes and the spleen (SP), they
      were more pronounced in the SP. Unlike DO11.10 mice, transgenic T cells in the
      chimera acquired an effector/memory phenotype upon antigen challenge. These
      results reveal a pliable model to study the impact of the constriction of the Tn
      cell repertoire upon optimal vaccine responses in the elderly.

PMID- 17015146
TI  - Haemorrhagic shock in mice--intracellular signalling and immunomodulation of
      peritoneal macrophages' LPS response.
AB  - Haemorrhagic shock leads to decreased proinflammatory cytokine response which is
      associated with an increased susceptibility to bacterial infections. In the
      present study, the effect of GM-CSF on lipopolysaccharide (LPS)-induced TNF-alpha
      release and MAPkinase activation was analysed on the background of a possible
      immunostimulating activity of this substance. Male BALB/c mice were bled to a
      mean arterial blood pressure of 50 mmHg for 45 min followed by resuscitation.
      Peritoneal macrophages were isolated 20 h after haemorrhage and incubated with 10
      ng/ml GM-CSF for 6h before LPS stimulation. TNF-alpha synthesis was studied in
      the culture supernatants using ELISA. Phosphorylation of ERK, p38MAPK and
      IkappaBalpha was detected by Western blotting. LPS-induced TNF-alpha production
      of peritoneal macrophages was significantly decreased 20 h after haemorrhage in
      comparison to the corresponding cells of sham-operated mice. In parallel the
      phosphorylation of IkappaBalpha was less in LPS-stimulated peritoneal macrophages
      from haemorrhagic mice. LPS-induced phosphorylation of ERK1/2 was also decreased
      in peritoneal macrophages isolated after haemorrhagic shock. In contrast, p38MAPK
      was phosphorylated more intensely after LPS-stimulation in macrophages collected
      from shocked mice. GM-CSF incubation elevated LPS-induced TNF-alpha response of
      macrophages from both sham-operated and shocked mice which was accompanied by an
      elevated IkappaB and ERK phosphorylation. In general, GM-CSF treatment in vitro
      enhanced peritoneal macrophages LPS-response both in terms of TNF-alpha synthesis
      and IkappaB and MAPK signalling, but the levels always stayed lower than those of
      GM-CSF-treated cells from sham-operated animals. In conclusion, GM-CSF
      preincubation could partly reactivate the depressed functions of peritoneal
      macrophages and may therefore exert immunostimulating properties after shock or
      trauma.

PMID- 17015147
TI  - Neem (Azadirachta indica) leaf preparation induces prophylactic growth inhibition
      of murine Ehrlich carcinoma in Swiss and C57BL/6 mice by activation of NK cells
      and NK-T cells.
AB  - We have reported earlier that pretreatment of mice with neem leaf preparation
      (NLP) causes prophylactic growth inhibition of murine Ehrlich's carcinoma (EC)
      and B16 melanoma. Using adoptive cell transfer technology, here we have
      established that NLP-mediated activation of immune cells may be involved in tumor
      growth restriction. Mononuclear cells from blood and spleen of NLP-activated
      Swiss and C57BL/6 mice causes enhanced cytotoxicity to murine EC cells in vitro.
      Fractionation of spleen cells exhibited greater percentage of tumor cell lysis in
      macrophage and B-cell-depleted NK and T-cell-rich fractions. Flow cytometric
      analysis revealed in both blood and spleen, NK cells (DX5+ or NK1.1+) and NK-T
      cells (CD3+/DX5+ or CD3+/NK1.1+) were increased in number in Swiss, C57BL/6 and
      athymic nude mice after pretreatment with NLP. NLP-stimulated spleen cells showed
      greater secretion of TNFalpha and IFNgamma. Thus, NLP-activated NK and NK-T cells
      in mice may regulate tumor cell cytotoxicity by enhancing the secretion of
      different cytotoxic cytokines.

PMID- 17015148
TI  - Analysis of IgE binding proteins of mesquite (Prosopis juliflora) pollen and
      cross-reactivity with predominant tree pollens.
AB  - Pollen from the mesquite tree, Prosopis juliflora, is an important source of
      respiratory allergy in tropical countries. Our aim was to partially characterize
      the IgE binding proteins of P. juliflora pollen extract and study cross
      reactivity with prevalent tree pollen allergens. Intradermal tests with P.
      juliflora and five other tree pollen extracts were performed on respiratory
      allergy patients from Bikaner (arid) and Delhi (semi arid). Prosopis extract
      elicited positive skin reactions in 71/220 of the patients. Sera were collected
      from 38 of these 71 patients and all demonstrated elevated specific IgE to P.
      juliflora. Immunoblotting with pooled patients' sera demonstrated 16 IgE binding
      components, with components of 24, 26, 29, 31, 35, 52, 58, 66 and 95 kDa
      recognized by more than 80% of individual patients' sera. P. juliflora extract is
      allergenically potent requiring 73 ng of self-protein for 50% inhibition of IgE
      binding in ELISA inhibition. Cross-inhibition assays showed close relationship
      among P. juliflora, Ailanthus excelsa, Cassia siamea and Salvadora persica. IgE
      binding components of 14, 41, 52 and 66 kDa were shared allergens whereas 26 and
      29 kDa were specific to P. juliflora. The findings suggest that purification of
      cross-reactive allergens will be helpful for diagnosis and immunotherapy of tree
      pollen allergic patients.

PMID- 17015149
TI  - Gene-specific signal joint modifications during V(D)J recombination of TCRAD
      locus genes in murine and human thymocytes.
AB  - V(D)J recombination assembles functional T-cell receptor (TCR) genes from V, D
      and J components in developing thymocytes. Extensive processing of V, D and J
      extremities before they are ligated creates a high degree of junctional diversity
      which results in the generation of a large repertoire of different TCR chains. In
      contrast, the extremities of the intervening DNA segment, which bear the
      recombination signal sequences, are generally held to be monomorphic, so that
      signal joints (SJs) consist of the perfect head-to-head juxtaposition of
      recombination signal extremities. We analyzed the structure of SJs generated
      during the recombination of TCRAD locus genes in murine and human thymocytes.
      Junctional diversity resulting from N nucleotide additions or from N nucleotide
      additions and base loss was found for each type of SJ examined. Different
      patterns of processing/modification were found, suggesting that different
      enzymatic activities operate during recombination of TCRA and TCRD genes,
      although they are located within the same genetic locus. Recombination of the
      deltaRec-1 element generates a diverse repertoire of SJs exhibiting both
      combinatorial and junctional diversity in murine and human thymocytes. Therefore,
      SJ diversity appears to be an intrinsic feature of V(D)J recombination in
      unmanipulated thymocytes.

PMID- 17015150
TI  - A novel RMRP mutation in a Spanish patient with cartilage-hair hypoplasia.
AB  - Cartilage-hair hypoplasia (CHH), or McKusick type metaphyseal chondrodysplasia,
      was first recognized as a distinct entity in the Old Order Amish in the USA, but
      was later identified in other groups, and found to be unusually frequent among
      Finns. CHH is highly pleiotropic with manifestations that include short stature,
      defective cellular immunity and predisposition to several cancers. CHH is caused
      by mutations in the RNA component of RNase MRP (RMRP, ribonuclease mitochondrial
      RNA processing) and is transmitted as an autosomal recessive trait. In the
      present work, a Spanish CHH patient was extensively characterized at the
      immunological and molecular DNA level. Several parameters of cellular and humoral
      immunity were analyzed in this patient: lymphocyte subpopulation, proliferative
      responsiveness in mitogen stimulation and quantification of serum
      immunoglobulins. Sequencing of the RMRP gene allowed identification of two
      mutations in the patient: a +4 C>T substitution previously described on one
      allele, and a duplication of 15 nucleotides at position -11 on the other allele.
      This mutation has not previously been described.

PMID- 17015151
TI  - Novel ways of preventing antibiotic-resistant infections: what might the future
      hold?
AB  - Most antibiotic-resistant bacteria are opportunistic pathogens; they colonize the
      skin and mucosal surfaces and only cause infection when the opportunity arises.
      Thus, the processes that lead to an infection attributable to antibiotic
      resistant bacteria can be broadly divided into those processes that lead to
      acquisition of antibiotic-resistant bacteria and those that lead to the
      development of an infection with that organism. We review the processes that lead
      to the development of infections attributable to antibiotic-resistant bacteria.
      We then discuss options that may become available to interrupt these processes
      and, thus, may reduce the rate of infections attributable to antibiotic-resistant
      bacteria in the future.

PMID- 17015152
TI  - Effectiveness of preemptive barrier precautions in controlling nosocomial
      colonization and infection by methicillin-resistant Staphylococcus aureus in a
      burn unit.
AB  - BACKGROUND: We report the effectiveness of preemptive enhanced barrier
      precautions in containing a methicillin-resistant Staphylococcus aureus (MRSA)
      outbreak in a university hospital burn unit and further controlling endemic
      nosocomial MRSA infection in the unit during the succeeding 27 months. METHODS:
      During a 6-month period, 12 patients in a 7-bed burn unit were found to be
      colonized (7) or infected (5) by MRSA. An epidemiologic study was undertaken.
      RESULTS: Seven of the 10 strains of MRSA from patients that were available for
      DNA typing were clonally identical. Early in the outbreak, a health care worker
      was found to be a concordant nasal carrier and was successfully decolonized with
      nasal mupirocin. However, despite stringent compliance with isolation of MRSA
      positive patients (targeted precautions), new cases of MRSA colonization or
      infection continued to occur. The outbreak was rapidly terminated after
      implementing preemptive barrier precautions with all patients in the unit: a new,
      clean gown and gloves for any physical contact with the patient or their
      environment. Although 25% of all nosocomial S aureus isolates in our hospital are
      resistant to methicillin, the incidence of endemic MRSA colonization and
      infection in the burn unit has remained very low since implementing barrier
      precautions unit wide (baseline rate, 2.2 [95% CI: 1.0-4.2] cases per 1000
      patient-days; outbreak rate, 7.2 [95% CI: 4.4-11.0] cases per 1000 patient-days;
      post-outbreak termination endemic rate, 1.1 (95% CI: 0.4-2.3) cases per 1000
      patient-days). The rate ratio comparing the outbreak and the baseline period was
      3.20 (95% CI: 1.40-7.95, P = .002); the rate ratio comparing the post-outbreak
      period with the baseline period was 0.48 (95% CI: 0.14-1.53, P = .10), and it has
      not been necessary to screen personnel for MRSA carriage to prevent nosocomial
      MRSA infections in this highly vulnerable population. CONCLUSION: Preemptive
      barrier precautions were highly effective in controlling the outbreak and, most
      notably, have also been highly effective in maintaining a very low incidence of
      nosocomial MRSA infection endemically in the succeeding 27 months of follow-up.
      Use of clean gloves, with or without a gown, bears consideration for all high
      risk hospitalized patients to prevent cross transmission of all multiresistant
      nosocomial pathogens.

PMID- 17015154
TI  - Knowledge, attitudes, and practices regarding antibiotic use among Latinos in the
      United States: review and recommendations.
AB  - Inappropriate use of antibiotics contributes to antimicrobial resistance
      worldwide. In Latin America, antibiotics are easily obtained over the counter. In
      the United States, the Latino population is the largest and fastest growing
      immigrant group. Hence, it is necessary to understand Latino cultural practices
      in regards to antibiotic use to develop effective interventions that reduce
      inappropriate antibiotic use among this population. We conducted a systematic
      review of descriptive and intervention studies measuring knowledge, attitudes,
      and practices of antibiotic use among Latinos in the United States. The search
      yielded only 11 descriptive studies and no interventions. The literature suggests
      that many Latinos in the United States self-prescribe antibiotics because of
      financial and sociocultural barriers and inaccurately believe that antibiotics
      help treat viral infections. Increased access to health care and appropriate
      culturally tailored interventions specific to Latinos are needed to promote
      judicious antibiotic use among Latinos.

PMID- 17015153
TI  - Effectiveness of barrier precautions and surveillance cultures to control
      transmission of multidrug-resistant organisms: a systematic review of the
      literature.
AB  - BACKGROUND: Despite the priority placed on preventing transmission of multidrug
      resistant organisms (MDROs) in health care facilities, there is a lack of
      consensus among recommended infection control guidelines. We focused on control
      measures that have a great potential to affect patient care, patient services,
      and hospital cost/resources: barrier precautions/patient isolation and
      surveillance cultures. METHODS: We conducted a systematic review of the
      literature and published English-language guidelines pertaining to the use of
      barrier precautions/patient isolation and surveillance cultures to prevent the
      transmission of MDROs. The recommendations made by the published guidelines were
      summarized and compared. The primary research studies identified through our
      literature search were evaluated for study quality. We then summarized the
      outcomes of the studies with the highest quality scores and made recommendations
      for future work. RESULTS: A total of 29 studies were included in our assessment
      of study quality; of those, 7 studies were of high quality. CONCLUSION: This
      systematic review identified key gaps in the literature including a need for
      greater monitoring of implementation of the interventions, more cost analyses of
      interventions, determining the independent contribution of specific
      interventions, and identifying the minimum interventions needed to reduce
      transmission.

PMID- 17015155
TI  - Translating evidence into practice to prevent central venous catheter-associated
      bloodstream infections: a systems-based intervention.
AB  - BACKGROUND: The central venous catheter (CVC) is a necessary, yet inherently
      risky, modern medical device. We aimed to carry out a systems-based intervention
      designed to facilitate the use of maximal sterile barrier precautions and the use
      of chlorhexidine for skin antisepsis during insertion of CVC. METHODS: All
      patients in whom a CVC was inserted at a medical-surgical intensive care unit at
      a university-affiliated public hospital were included in a before-after trial.
      The standard CVC kit in routine use before the intervention included a small
      sterile drape (24" by 36") and 10% povidone-iodine for skin antisepsis. We
      special ordered a customized kit that, instead, included a large sterile drape
      (41" by 55") and 2% chlorhexidine gluconate in 70% isopropyl alcohol. Both the
      standard kit in use before the intervention and the customized kit included
      identical CVCs. Baseline data included the quarterly CVC-associated bloodstream
      infection (BSI) rates during the 15 months before the intervention. Comparison
      data included the quarterly CVC-associated BSI rates during the 15 months after
      we instituted exclusive use of the customized kit. RESULTS: The mean quarterly
      CVC-associated BSI rate decreased from a baseline of 11.3 per 1000 CVC-days
      before the intervention to 3.7 per 1000 CVC-days after the intervention (P <
      .01). Assuming direct costs of at least 10,000 dollars per CVC-associated BSI, we
      calculated resultant annualized savings to the hospital of approximately 350,000
      dollars. CONCLUSION: Infection control interventions that rely on voluntary
      changes in human behavior, despite the best intentions of us all, are often
      unsuccessful. We have demonstrated that a systems-based intervention led to a
      sustained decrease in the CVC-associated BSI rate, thereby resulting in improved
      patient safety and decreased cost of care.

PMID- 17015156
TI  - Translating infection prevention evidence into practice using quantitative and
      qualitative research.
AB  - Infection control professionals and hospital epidemiologists, using the valid
      methods of applied epidemiology-surveillance, benchmarking, intervention,
      evaluation--have largely been responsible for dramatically reducing the incidence
      of health care-associated infections over the past several decades. However, we
      believe that the field of infection control can--and should--also be a leader in
      understanding how research findings can be efficiently and effectively translated
      into clinical practice. Unfortunately, there is no current reliable information
      about which preventive practices are being used in US hospitals to prevent common
      device-related infections. If we are to understand how best to translate research
      into practice, the reasons hospitals are using some preventive practices-or are
      not-must be explored more fully. This article provides a framework for one
      proposed research endeavor to promote the successful translation of proven
      infection prevention practices and a subsequent decrease in health care
      associated infections. In addition, we hope that this article will stimulate
      increased interest and research in identifying strategies that will successfully
      move evidence from the peer-reviewed literature to the patient's bedside.

PMID- 17015157
TI  - An evaluation of patient area cleaning in 3 hospitals using a novel targeting
      methodology.
AB  - BACKGROUND: Although environmental cleaning and disinfecting practices have
      become a cornerstone of patient care, assessment of actual compliance with such
      procedures has not been reported. Using a novel methodology, we developed a means
      to monitor directly such activities. METHODS: A nontoxic target solution, which
      intensely fluoresces with a black light, was formulated to be inconspicuous yet
      readily removed by housekeeping products. Small volumes of material were
      confidentially applied to 12 target sites in patient rooms in 3 hospitals
      following terminal cleaning. The targets were reevaluated following terminal
      cleaning after several patients had occupied the room. RESULTS: One hundred fifty
      seven rooms and 1404 targets were evaluated. In the 3 hospitals studied, only
      45%, 42%, and 56% of targets were removed by routine terminal
      cleaning/disinfecting activities. The frequency with which various individual
      sites were cleaned varied widely but was similar in all hospitals. CONCLUSION:
      The use of a novel target compound to evaluate housekeeping practices confirmed
      high rates of cleaning of traditional sites but poor cleaning of many sites that
      have significant potential for harboring and transmitting microbial pathogens.
      This methodology has the potential for being used to evaluate objectively the
      cleaning/disinfecting activities in various health care settings.

PMID- 17015158
TI  - Influence of amoebae and physical and chemical characteristics of water on
      presence and proliferation of Legionella species in hospital water systems.
AB  - The reservoir for hospital-acquired Legionnaires' disease has been shown to be
      the potable water distribution system. The objectives of the present study were
      as follows: (1) to examine the possible relationship between physical-chemical
      characteristics of water such as temperature, pH, hardness, conductivity, and
      residual chlorine and the presence of amoebae as growth-promoting factors for
      Legionella species and (2) to determine eradication measures for water
      distribution systems to seek ways of reducing the risk of legionellosis. Ten
      hospitals in southwest France took part in this study. Water samples were
      collected from 106 hot water faucets, showers, hot water tanks, and cooling
      towers. Two analyses were performed to analyze the association between water
      characteristics and (1) the presence of Legionella species and (2) the
      proliferation of Legionella species. Of the 106 water samples examined, 67
      (63.2%) were positive for Legionella species. Amoebae were detected in 73 of 106
      (68.9%) samples and in 56 of 67 (86.6%) Legionella species-positive samples (P <
      10(-6)). In these positive samples, conductivity was lower than 500 microOmega(
      1).cm(-1) in 58.2% (P = .026), temperature was below 50 degrees C in 80.6% (P =
      .004), and hardness was significantly higher (P = 002) than in Legionella species
      negative samples. Neither Legionella species nor amoebae were isolated from any
      sampling point in which the water temperature was above 58.8 degrees C.
      Multivariate analysis shows that high hardness and presence of amoebae were
      strongly correlated statistically with the presence of Legionella when showers,
      tanks, pH, and temperature promoted their proliferation. This study shows the
      importance of water quality evaluation in assessing environmental risk factors
      and in selecting the most appropriate prevention and control measures in hospital
      water systems.

PMID- 17015159
TI  - Significant pathogens isolated from surgical site infections at a community
      hospital in the Midwest.
AB  - BACKGROUND: Studies examining the incidence of microorganisms isolated from
      surgical site infections (SSIs) have been conducted primarily at large academic
      health care centers. Results from these studies have revealed that methicillin
      resistant Staphylococcus aureus (MRSA) has emerged as a significant pathogen in
      SSIs. Minimal data are available from smaller, community hospitals on the
      incidence of microorganisms associated with SSIs, particularly the incidence of
      MRSA in SSIs. METHODS: A retrospective study was performed to identify the
      microorganisms associated with SSIs in patients who underwent class I and II
      surgeries at a small urban to rural community hospital from January 2003 through
      December 2004. RESULTS: A total of 10,672 surgeries was performed, and 89 SSIs
      were identified. Staphylococcus aureus was the most common pathogen (25.8%).
      Enterobacteriaceae were the second most frequently isolated organisms (12.4%),
      followed by streptococci species (11.2%), coagulase-negative staphylococci
      (10.1%), enterococci species (7.9%), and Pseudomonas aeruginosa (6.7%). MRSA was
      isolated from 4.5% of the SSIs. CONCLUSION: We have demonstrated that the
      spectrum of microorganisms isolated in SSIs at a community hospital is comparable
      with that reported in studies conducted at large academic health care centers,
      including the emergence of MRSA as a pathogen in SSIs. This information will
      guide future infection control initiatives to reduce SSIs.

PMID- 17015160
TI  - Attitudes, beliefs, and infection control practices of Iranian dentists
      associated with HIV-positive patients.
AB  - Of the 309 private dental practitioners in Fars, Iran, surveyed most, 77.7%
      believed they had a professional duty to treat HIV-positive patients, with 61.4%
      expressing some level of discomfort about treating these patients, and 75.1%
      believed they should be treated at a specialist practice. Gloves and masks were
      not always worn, 15.8% and 9.7%, respectively, and 70.2% of dentist washed their
      hands before treatment and 60.2% after treatment. Elementary standard precautions
      were not routinely implemented in private dental practices, despite high levels
      of concerns about transmission of infection.

PMID- 17015161
TI  - Colonization and infection with vancomycin-resistant Enterococcus among patients
      with cancer.
AB  - Vancomycin-resistant enterococci (VRE) cause substantial morbidity and mortality
      in immune-suppressed patients. In a retrospective review, VRE fecal colonization
      was documented in 4.7% (99 of 2115) of patients screened, with 5.4% of patients
      with leukemia, 4.9% of hematopoietic stem cell transplantation recipients, and
      2.2% of patients with lymphoma being colonized. Among the 99 patients with VRE
      colonization, 29 (29.29%) developed bacteremia, and there were 32 episodes of VRE
      infection at other sites. The rate of VRE bacteremia in solid tumor patients
      (0.12%) was significantly lower (P <or= .0001). VRE colonization had a negative
      predictive value of 99.9% and a positive predictive value of 29.3% for the
      development of VRE bacteremia and might help identify a high-risk subset of
      patients that might benefit from preemptive VRE therapy during episodes of
      neutropenic fever.

PMID- 17015162
TI  - Measurement and feedback of infection control process measures in the intensive
      care unit: Impact on compliance.
AB  - BACKGROUND: Infection control process measures provide actionable and measurable
      indicators for performance improvement. OBJECTIVE: To determine the relationship
      between the measurement and feedback of selected infection control process
      measures and compliance with infection control practices. METHODS: We measured
      selected infection control process measures (hand hygiene, femoral catheter use
      as a proportion of all central venous catheter (CVC) days and proportion of head
      of bed elevations) in the medical respiratory intensive care unit (ICU) (MRICU)
      and the surgical trauma ICU (STICU). All data were collected by trained infection
      control practitioners. Baseline data were obtained April through June 2004.
      Baseline hand hygiene data were obtained from May to June. Follow-up observations
      were obtained from July 2004 through March 2005. Both baseline and follow-up
      observations were reported to the units' leadership. The data were reviewed for
      improvement in compliance with process measures. Differences in proportions were
      analyzed for statistical significance by the chi(2) test. RESULTS: There was a
      statistically significant improvement in the head of bed elevation rates: 54.9%
      versus 98.4% (P < .001) for the MRICU and 46.5% versus 77.2% (P < .001) for the
      STICU, respectively. There was also a statistically significant decline in
      femoral catheter rates in both ICUs: 17.8% versus 10% (P = .001) in the MRICU and
      8.4% versus 3% (P < .001) in the STICU, respectively. There was no significant
      improvement in hand hygiene rates in either ICU: 31.8% versus 39.3% (P = .1) in
      the MRICU and 50% versus 50.3% (P = .9) in the STICU, respectively. CONCLUSION:
      Feedback of process measures lowered the use of femoral catheters and improved
      the proportion of elevated head of beds in 2 ICUs, but there was no significant
      improvement in hand hygiene.

PMID- 17015163
TI  - Capnocytophaga canimorsus meningitis after routine myelography: a sentinel event
      identifies multiple opportunities for improvement of standard practices in
      radiology.
AB  - Meningitis developed after a routine myelogram in a healthy patient. When
      Capnocytophaga canimorsus was identified, investigations revealed that the
      patient, the radiologist, and the staff were all dog owners. Multiple deviations
      from recommended practices in radiology were identified and corrected. The
      investigation of an unusual sentinel event allowed multiple interventions to be
      implemented simultaneously, with resultant risk reduction for subsequent
      radiologic procedures.

PMID- 17015164
TI  - Superoxide dismutase overexpression and cellular oxidative damage in diabetes. A
      commentary on "Overexpression of mitochondrial superoxide dismutase in mice
      protects the retina from diabetes-induced oxidative stress".

PMID- 17015165
TI  - Overexpression of mitochondrial superoxide dismutase in mice protects the retina
      from diabetes-induced oxidative stress.
AB  - The retina experiences mitochondrial dysfunction in diabetes, superoxide levels
      are elevated, and mitochondrial superoxide dismutase (MnSOD) activity is
      decreased. Inhibition of superoxide accumulation in diabetes prevents
      mitochondrial dysfunction, apoptosis of retinal capillary cells, and the
      development of retinal histopathology. The purpose of this study is to examine
      the effect of overexpression of MnSOD on oxidative stress, DNA damage, and
      nitrative stress in the retina of diabetic mice. After 7 weeks of diabetes in
      MnSOD overexpressing (hemizygous) mice (MnSOD-Tg) and in their age-matched
      nontransgenic mice, parameters of oxidative stress and nitrative stress were
      measured in the retina. Overexpression of MnSOD prevented diabetes-induced
      decreases in retinal GSH levels and the total antioxidant capacity. In the same
      retina, MnSOD overexpression also inhibited diabetes-induced increases in the
      levels of 8-OHdG and nitrotyrosine. This suggests that MnSOD could be implicated
      in the pathogenesis of retinopathy by protecting the retina from increased
      oxidative damage experienced in diabetic conditions. Thus, understanding how
      changes in mitochondrial function result in the development of diabetic
      retinopathy could help identify SOD mimics to inhibit its development.

PMID- 17015166
TI  - Suppression of UVA-mediated release of labile iron by epicatechin--a link to
      lysosomal protection.
AB  - UVA (320-380 nm) radiation generates an oxidative stress in cells and leads to an
      immediate release of potentially damaging labile iron pools in human skin cells.
      Treatment of cultured skin fibroblasts for several hours with physiologically
      relevant concentrations of either epicatechin (EC), a flavonoid plant constituent
      present in foods, or methylated epicatechin (3'-O-methyl epicatechin, MeOEC), its
      major human metabolite, prevents this iron release. The similarity of the
      effectiveness of EC and MeOEC argues against chelation as the mechanism of iron
      removal. Evidence based on measurements of lysosomal integrity strongly supports
      the hypothesis that the catechins protect against lysosomal destruction by UVA.
      Such damage would normally lead to protease release, which has been previously
      shown to cause ferritin degradation and release of labile iron.

PMID- 17015167
TI  - Sunscreen enhancement of UV-induced reactive oxygen species in the skin.
AB  - The number of UV-induced (20 mJ cm(-2)) reactive oxygen species (ROS) generated
      in nucleated epidermis is dependent upon the length of time the UV filter
      octocrylene, octylmethoxycinnamate, or benzophenone-3 remains on the skin
      surface. Two-photon fluorescence images acquired immediately after application of
      each formulation (2 mg cm(-2)) to the skin surface show that the number of ROS
      produced is dramatically reduced relative to the skin-UV filter control. After
      each UV filter remains on the skin surface for t=20 min, the number of ROS
      generated increases, although it remains below the number generated in the
      control. By t=60 min, the filters generate ROS above the control. The data show
      that when all three of the UV filters penetrate into the nucleated layers, the
      level of ROS increases above that produced naturally by epidermal chromophores
      under UV illumination.

PMID- 17015168
TI  - P-glycoprotein induction: an antidotal pathway for paraquat-induced lung
      toxicity.
AB  - The widespread use of the nonselective contact herbicide paraquat (PQ) has been
      the cause of thousands of deaths from both accidental and voluntary ingestion.
      The main target organ for PQ toxicity is the lung. No antidote or effective
      treatment to decrease PQ accumulation in the lung or to disrupt its toxicity has
      yet been developed. The present study describes a procedure that leads to a
      remarkable decrease in PQ accumulation in the lung, together with an increase in
      its fecal excretion and a subsequent decrease in several biochemical and
      histopathological biomarkers of toxicity. The administration of dexamethasone
      (100 mg/kg ip) to Wistar rats, 2 h after PQ intoxication (25 mg/kg ip), decreased
      the lung PQ accumulation to about 40% of the group exposed to only PQ and led to
      an improvement in tissue healing in just 24 h as a result of the induction of de
      novo synthesis of P-glycoprotein (P-gp). The involvement of P-gp in these effects
      was confirmed by Western blot analysis and by the use of a competitive inhibitor
      of this transporter, verapamil (10 mg/kg ip), which, given 1 h before
      dexamethasone, blocked its protective effects, causing instead an increase in
      lung PQ concentration and an aggravation of toxicity. In conclusion, the
      induction of P-gp, leading to a decrease in lung levels of PQ and the consequent
      prevention of toxicity, seems to be a new and promising treatment for PQ
      poisonings that should be further clinically tested.

PMID- 17015169
TI  - The intracellular genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone mediates
      G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling
      pathway.
AB  - The cellular actions of genistein are believed to mediate the decreased risk of
      breast cancer associated with high soy consumption. We have investigated the
      intracellular metabolism of genistein in T47D tumorigenic and MCF-10A
      nontumorigenic cells and assessed the cellular actions of resultant metabolites.
      Genistein selectively induced growth arrest and G2-M phase cell cycle block in
      T47D but not MCF10A breast epithelial cells. These antiproliferative effects were
      paralleled by significant differences in the association of genistein to cells
      and in particular its intracellular metabolism. Genistein was selectively taken
      up into T47D cells and was subject to metabolism by CYP450 enzymes leading to the
      formation of both 5,7,3',4'-tetrahydroxyisoflavone (THIF) and two glutathionyl
      conjugates of THIF. THIF inhibited cdc2 activation via the phosphorylation of p38
      MAP kinase, suggesting that this species may mediate genistein's cellular
      actions. THIF exposure activated p38 and caused subsequent inhibition of cyclin
      B1 (Ser 147) and cdc2 (Thr 161) phosphorylation, two events critical for the
      correct functioning of the cdc2-cyclin B1 complex. We suggest that the formation
      of THIF may mediate the cellular actions of genistein in tumorigenic breast
      epithelial cells via the activation of signaling through p38.

PMID- 17015170
TI  - One-electron reduction of S-nitrosothiols in aqueous medium.
AB  - One-electron reduction of S-nitrosothiols (RSNO) has been studied using
      radiolytically produced reducing entity, the hydrated electron (e(aq)(-)), in
      aqueous medium. Both kinetics of the reaction and the mechanistic aspects of the
      decomposition of S-nitroso derivatives of glutathione, L-cysteine, N-acetyl-L
      cysteine, N-acetyl-D,L-penicillamine, N-acetylcysteamine, L-cysteine methyl
      ester, and D,L-penicillamine have been investigated at neutral and acidic pH. The
      second-order rate constants of the reaction of e(aq)(-) with RSNOs were
      determined using a pulse radiolysis technique and were found to be diffusion
      controlled (10(10) dm(3) mol(-1) s(-1)) at neutral pH. The product analysis using
      HPLC, fluorimetry, and MS revealed the formation of thiol and nitric oxide as the
      major end products. It is therefore proposed that one-electron reduction of RSNO
      leads to the liberation of NO. There is no intermediacy of a thiyl radical as in
      the case of oxidation reactions of RSNOs. The radical anion of RSNO (RSN(*)O(-))
      is proposed as a possible intermediate. The overall reaction could be written as
      RSNO + e(aq)(-) --H+--> RSH + (*)NO.

PMID- 17015171
TI  - Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage.
AB  - Procyanidins can exert cytoprotective, anti-inflammatory, and anticarcinogenic
      actions in the gastrointestinal tract. Previous evidence has shown that
      procyanidins can interact with synthetic membranes and protect them from
      oxidation and disruption. Thus, in this study we investigated the capacity of a
      hexameric procyanidin fraction (Hex) isolated from cocoa to protect Caco-2 cells
      from deoxycholic (DOC)-induced cytotoxicity, cell oxidant increase, and loss of
      monolayer integrity. Hex interacted with the cell membranes without affecting
      their integrity, as evidenced by a Hex-mediated increase in the transepithelial
      electrical resistance, and inhibition of DOC-induced cytotoxicity. DOC induced an
      increase in cell oxidants, alterations in the paracellular transport, and
      redistribution of the protein ZO-1 from cell-cell contacts into the cytoplasm.
      Hex partially inhibited all these events at concentrations ranging from 2.5 to 20
      microM. Similarly, Hex (5-10 microM) inhibited the increase in cell oxidants, and
      the loss of integrity of polarized Caco-2 cell monolayers induced by a lipophilic
      oxidant (2,2'-azobis (2,4-dimethylvaleronitrile). Results show that the assayed
      procyanidin fraction can interact with cell membranes and protect Caco-2 cells
      from DOC-induced cytotoxicity, oxidant generation, and loss of monolayer
      integrity. At the gastrointestinal tract, large procyanidins may exert beneficial
      effects in pathologies such us inflammatory diseases, alterations in intestinal
      barrier permeability, and cancer.

PMID- 17015172
TI  - Distribution of macular xanthophylls between domains in a model of photoreceptor
      outer segment membranes.
AB  - A model of photoreceptor outer segment (POS) membranes has been proposed,
      consisting of an equimolar ternary mixture of 1-palmitoyl-2
      docosahexaenoylphosphatidylcholine/distearoylphosphatidylcholine/cholesterol. It
      was shown that, as in membranes made from the raft-forming mixture, in the model
      of POS membranes, two domains are formed: the raft domain (detergent resistant
      membranes, DRM), and the bulk domain (detergent soluble membranes, DSM).
      Saturation-recovery EPR discrimination by oxygen transport method also
      demonstrated the presence of two domains in this model system in situ at a wide
      range of temperatures (10-55 degrees C), showing additionally that neither lutein
      nor zeaxanthin at 1 mol% affect the formation of these domains. These membrane
      domains have been separated using cold Triton X-100 extraction from a model of
      POS membranes containing 1 mol% of either lutein or zeaxanthin. The results
      indicated that the macular xanthophylls lutein and zeaxanthin are substantially
      excluded from DRM and remain concentrated in DSM, a domain enriched in highly
      unsaturated docosahexaenoyl acid which is abundant in retina membranes. The
      concentration of xanthophylls in DRM and DSM calculated as the mol ratio of
      either xanthophyll to total lipid (phospholipid+cholesterol) was 0.0028 and
      0.0391, respectively. Thus, xanthophylls are about 14 times more concentrated in
      DSM than in DRM. No significant difference in the distribution of lutein and
      zeaxanthin was found. The obtained results suggest that in POS membranes macular
      xanthophylls should also be concentrated in domains enriched in polyunsaturated
      chains.

PMID- 17015173
TI  - One-electron oxidation of catecholamines generates free radicals with an in vitro
      toxicity correlating with their lifetime.
AB  - One-electron oxidation of dopamine by ferricyanide generates a highly reactive
      free radical intermediate that inactivates the V-type H(+)-ATPase proton pump in
      catecholamine storage vesicles, i.e., the driving force in both the vesicular
      uptake and the storage of catecholamines, in a cell-free in vitro model system at
      pH 7.0. Electron paramagnetic resonance spectroscopy revealed that a radical with
      g=2.0045, formed by this oxidation, was relatively long-lived (t(1/2) obs=79 s at
      pH 6.5 and 25 degrees C). Experimental evidence is presented that the observed
      radical most likely represents dopamine semiquinone free radical, although an o
      quinone free radical cannot be ruled out. Oxidation of noradrenaline and
      adrenaline by ferricyanide generated similar isotropic radicals, but of shorter
      half-lives (i.e., 43 and 5.3 s, respectively), and the efficacy of inactivation
      of the H(+)-ATPase correlated with the half-life of the respective catecholamine
      free radical (i.e., dopamine >noradrenaline>>adrenaline). Thus, the generation of
      relatively long-lived semiquinone free radicals, although at low concentrations,
      in dopaminergic and noradrenergic neurons may represent a common mechanism of
      cytotoxicity linked to neurodegeneration of the respective neurons related to
      Parkinson disease.

PMID- 17015174
TI  - Free radical scavenging action of the natural polyamine spermine in rat liver
      mitochondria.
AB  - The isoflavonoid genistein, the cyclic triterpene glycyrrhetinic acid, and
      salicylate induce mitochondrial swelling and loss of membrane potential (Delta
      Psi) in rat liver mitochondria (RLM). These effects are Ca(2+)-dependent and are
      prevented by cyclosporin A and bongkrekik acid, classic inhibitors of
      mitochondrial permeability transition (MPT). This membrane permeabilization is
      also inhibited by N-ethylmaleimide, butylhydroxytoluene, and mannitol. The above
      mentioned pro-oxidants also induce an increase in O(2) consumption and H(2)O(2)
      generation and the oxidation of sulfhydryl groups, glutathione, and pyridine
      nucleotides. All these observations are indicative of the induction of MPT
      mediated by oxidative stress. At concentrations similar to those present in the
      cell, spermine can prevent swelling and Delta Psi collapse, that is, MPT
      induction. Spermine, by acting as a free radical scavenger, in the absence of
      Ca(2+) inhibits H(2)O(2) production and maintains glutathione and sulfhydryl
      groups at normal reduced level, so that the critical thiols responsible for pore
      opening are also consequently prevented from being oxidized. Spermine also
      protects RLM under conditions of accentuated thiol and glutathione oxidation,
      lipid peroxidation, and protein oxidation, suggesting that its action takes place
      by scavenging the hydroxyl radical.

PMID- 17015175
TI  - Inhibition of xanthine oxidase improves myocardial contractility in patients with
      ischemic cardiomyopathy.
AB  - Reactive oxygen species, in particular superoxide, have been closely linked to
      the underlying pathophysiology of ischemic cardiomyopathy: superoxide not only
      mediates mechanoenergetic uncoupling of the myocyte but also adversely impacts on
      myocardial perfusion by depleting endothelial-derived nitric oxide
      bioavailability. Xanthine oxidase generates superoxide upon oxidation of
      hypoxanthine and xanthine and has been detected in cardiac myocytes and coronary
      endothelial cells of patients with ischemic heart disease. Here we investigated
      the effects of oxypurinol, a xanthine oxidase inhibitor, on myocardial
      contractility in patients with ischemic cardiomyopathy. Twenty patients (19
      males, 66+/-8 years) with stable coronary disease, severely suppressed systolic
      function (left ventricular ejection fraction 22+/-2%), and nonelevated uric acid
      plasma levels received a single intravenous dose of oxypurinol (400 mg). Cardiac
      MRI studies, performed before and 5.2+/-0.9 h after oxypurinol administration,
      revealed a reduction in end-systolic volumes (-9.7+/-4.2%; p=0.03) and an
      increase in left ventricular ejection fraction (+17.5+/-5.2%; p=0.003), whereas 6
      patients (6 males, 63+/-3.8 years, ejection fraction 26+/-5%) who received
      vehicle only did not show significant changes in any of the parameters studied.
      Oxypurinol improves left ventricular function in patients with ischemic
      cardiomyopathy. These results underscore the significance of reactive oxygen
      species as important pathophysiological mediators in ischemic heart failure and
      point toward xanthine oxidase as an important source of reactive species that
      serve to modulate the myocardial redox state in this disease.

PMID- 17015176
TI  - Apocynin normalizes hyperreactivity to phenylephrine in mesenteric arteries from
      cholesterol-fed mice by improving endothelium-derived hyperpolarizing factor
      response.
AB  - We studied the relationship among endothelial function, oxidative stress, and
      phenylephrine (PE; alpha(1)-adrenoceptor agonist)-induced contraction in
      mesenteric arteries from high-cholesterol (HC)-diet-fed mice. In HC mice (vs age
      matched normal-diet-fed mice): (1) PE-induced contraction in endothelium-intact
      rings was enhanced (endothelial denudation increased contraction in "normal-diet"
      rings, but did not enhance it further in "HC" rings); (2) the enhanced PE-induced
      contraction was further enhanced in the presence of N(G)-nitro-L-arginine (L-NNA;
      nitric oxide synthase inhibitor) or L-NNA plus indomethacin (cyclooxygenase
      inhibitor) [to preserve endothelium-derived hyperpolarizing factor (EDHF)], but
      unchanged in the presence of charybdotoxin plus apamin (to block EDHF); (3) ACh
      induced EDHF-type relaxation was reduced; and (4) oxidative stress [indicated by
      the plasma 8-isoprostane level (reliable systemic marker) and aortic superoxide
      production] was greater. In HC mice, PE-induced contraction was normalized by
      apocynin [NAD(P)H oxidase inhibitor] or tempol (superoxide dismutase mimetic),
      but enhanced by NADH [NAD(P)H oxidase substrate]. Oral dietary supplementation
      with apocynin (30 mg/kg/day for 4 weeks) corrected the above abnormalities.
      Hence: (1) PE-induced contraction is modulated by the endothelium, and the
      enhanced contractility in HC mice results from defective EDHF signaling and
      elevated oxidative stress, and (2) apocynin normalizes PE-induced contraction in
      HC mice by improving EDHF signaling.

PMID- 17015177
TI  - Early activation of bradykinin B2 receptor aggravates reactive oxygen species
      generation and renal damage in ischemia/reperfusion injury.
AB  - The kallikrein/kinin system is beneficial in ischemia/reperfusion injury in
      heart, controversial in brain, but detrimental in lung, liver, and intestine. We
      examined the role of the kallikrein/kinin system in acute ischemia/reperfusion
      renal injury induced by 40 min occlusion of the renal artery followed by
      reperfusion. Rats were infused with tissue kallikrein protein 5 days before
      (pretreated group) or after (treated group) ischemia. Two days later, the
      pretreated group exhibited the worst renal dysfunction, followed by the treated
      group, then the control group. Kallikrein increased tubular necrosis and
      inflammatory cell infiltration with generation of more tumor necrosis factor
      alpha and monocyte chemoattractant protein-1. Reactive oxygen species (ROS),
      malondialdehyde, and reduced/oxidized glutathione measurement revealed that the
      oxidative stress was augmented by kallikrein administration in both ischemic and
      reperfusion phases. The groups with more ROS generation also had more apoptotic
      renal cells. The deleterious effects of kallikrein on ischemia/reperfusion injury
      were reversed by cotreatment with bradykinin B2 receptor (B2R) antagonist, but
      not B1 receptor antagonist, and were not associated with hemodynamic changes. We
      conclude that early activation of B2R augmented ROS generation in
      ischemia/reperfusion renal injury, resulting in subsequent apoptosis,
      inflammation, and tissue damage. This finding suggests the potential application
      of B2R antagonists in acute ischemic renal disease associated with bradykinin
      activation.

PMID- 17015178
TI  - Reduced nonprotein thiols inhibit activation and function of MMP-9: implications
      for chemoprevention.
AB  - Clinical studies demonstrate a positive correlation between the extent of matrix
      metalloproteinase (MMP) activation and malignant progression of precancerous
      lesions. Therefore, identification of effective, well-tolerated MMP inhibitors
      represents a rational chemopreventive strategy. A variety of agents, including
      proteinases and thiol-oxidizing compounds, activate MMPs by initiating release of
      the propeptide's cysteine sulfur "blockage" of the MMP active site. Despite the
      importance of the propeptide's cysteine thiol in preserving MMP latency, limited
      studies have evaluated the effects of reduced thiols on MMP function. This study
      investigated the effects of two naturally occurring nonprotein thiols, i.e.,
      glutathione (GSH) and N-acetylcysteine (NAC), on activation, function, and
      cellular-extracellular matrix interactions of the basement-membrane-degrading
      gelatinase, MMP-9. Our results reveal that NAC and GSH employ protein S
      thiolation to inhibit organomercurial activation of pro-MMP-9. Gelatinase
      activity assays showed that GSH and NAC significantly inhibited MMP-9 but not MMP
      2 function, implying isoform structural specificity. Immunoblot analyses, which
      suggested GSH interacts with MMP-9's active-site Zn, were corroborated by
      computational molecular modeling. Cell invasion assays revealed that NAC enhanced
      endostatin's ability to inhibit human cancer cell invasion. Collectively, these
      data demonstrate that nonprotein thiols suppress MMP-9 activation and function
      and introduce the prospect for their use in chemopreventive applications.

PMID- 17015179
TI  - Rate of oxidant stress regulates balance between rat gastric mucosa proliferation
      and apoptosis.
AB  - We have characterized an experimental model of ethanol-induced chronic gastritis
      in which a compensatory mucosal cell proliferation is apparently regulated by
      lipoperoxidative events. Therefore, the present study is an attempt to further
      assess the participation of oxidant stress during gastric mucosa proliferation,
      by administering alpha-tocopherol (vitamin E) to rats with gastritis. A
      morphometric analysis was done, and parameters indicative of oxidant stress,
      cellular proliferation (including cyclin D1 levels), apoptotic events, and
      activities of endogenous antioxidant systems were measured in gastric mucosa from
      our experimental groups. After ethanol withdrawal, restitution of surface
      epithelium coincided with increased lipid peroxidation and cell proliferation and
      further active apoptosis. High alpha-tocopherol dosing (100 IU/kg bw) showed a
      clear antioxidant effect, abolished cell proliferation, and promoted an early and
      progressive apoptosis, despite vitamin E also enhancing levels of endogenous
      antioxidants. Indicators of cell proliferation inversely correlated with
      apoptotic events, and this relationship was blunted by administering vitamin E,
      probably by affecting translocation of active cyclin D1 into the nucleus. In
      conclusion, alpha-tocopherol administration inhibited cell proliferation, leading
      to a predominance of apoptotic events in ethanol-induced gastric damage.
      Therefore, the timing and magnitude of lipoperoxidative events seemed to
      synchronize in vivo cell proliferative and apoptotic events, probably by changing
      the cell redox state.

PMID- 17015181
TI  - Neural mechanism for stochastic behaviour during a competitive game.
AB  - Previous studies have shown that non-human primates can generate highly
      stochastic choice behaviour, especially when this is required during a
      competitive interaction with another agent. To understand the neural mechanism of
      such dynamic choice behaviour, we propose a biologically plausible model of
      decision making endowed with synaptic plasticity that follows a reward-dependent
      stochastic Hebbian learning rule. This model constitutes a biophysical
      implementation of reinforcement learning, and it reproduces salient features of
      behavioural data from an experiment with monkeys playing a matching pennies game.
      Due to interaction with an opponent and learning dynamics, the model generates
      quasi-random behaviour robustly in spite of intrinsic biases. Furthermore, non
      random choice behaviour can also emerge when the model plays against a non
      interactive opponent, as observed in the monkey experiment. Finally, when
      combined with a meta-learning algorithm, our model accounts for the slow drift in
      the animal's strategy based on a process of reward maximization.

PMID- 17015182
TI  - Postprandial modulation of serum paraoxonase activity and concentration in
      diabetic and non-diabetic subjects.
AB  - OBJECTIVES: To analyse the HDL associated anti-oxidant enzyme paraoxonase-1,
      during postprandial hyperlipaemia. METHODS AND RESULTS: Type 2 diabetic patients
      (n=72), glucose intolerant patients (n=10) and controls (n=38) consumed a high
      fat:high carbohydrate meal. Blood samples were collected up to 4h and analysed
      for lipids and paraoxonase-1. In vitro studies examined HDL function with respect
      to the enzyme. There were significant postprandial increases in serum
      triglycerides. Paraoxonase-1 activity decreased significantly throughout the
      postprandial phase. Concentrations of the enzyme initially decreased
      significantly, but returned to fasting concentrations at 4h. Specific activities
      were significantly lower at 4h, compared to fasting. The decrease in specific
      activity was linked to the dynamic phase of postprandial lipoprotein metabolism.
      Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to
      postprandial conditions in vitro had reduced capacity to associate with and
      stabilise PON1. CONCLUSIONS: Postprandial hyperlipaemia was associated with
      changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential
      of HDL. No differences were observed between diabetic and non-diabetic patients,
      suggesting that the effect was linked to postprandial hyperlipaemia.
      Modifications to paraoxonase-1 could contribute to increased risk of vascular
      disease associated with postprandial lipaemia, particularly in diabetic patients,
      who are already deficient in serum paraoxonase-1.

PMID- 17015180
TI  - A new paradigm: manganese superoxide dismutase influences the production of H2O2
      in cells and thereby their biological state.
AB  - The principal source of hydrogen peroxide in mitochondria is thought to be from
      the dismutation of superoxide via the enzyme manganese superoxide dismutase
      (MnSOD). However, the nature of the effect of SOD on the cellular production of
      H(2)O(2) is not widely appreciated. The current paradigm is that the presence of
      SOD results in a lower level of H(2)O(2) because it would prevent the non
      enzymatic reactions of superoxide that form H(2)O(2). The goal of this work was
      to: a) demonstrate that SOD can increase the flux of H(2)O(2), and b) use kinetic
      modelling to determine what kinetic and thermodynamic conditions result in SOD
      increasing the flux of H(2)O(2). We examined two biological sources of superoxide
      production (xanthine oxidase and coenzyme Q semiquinone, CoQ(*-) that have
      different thermodynamic and kinetic properties. We found that SOD could change
      the rate of formation of H(2)O(2) in cases where equilibrium-specific reactions
      form superoxide with an equilibrium constant (K) less than 1. An example is the
      formation of superoxide in the electron transport chain (ETC) of the mitochondria
      by the reaction of ubisemiquinone radical with dioxygen. We measured the rate of
      release of H(2)O(2) into culture medium from cells with differing levels of
      MnSOD. We found that the higher the level of SOD, the greater the rate of
      accumulation of H(2)O(2). Results with kinetic modelling were consistent with
      this observation; the steady-state level of H(2)O(2) increases if K<1, for
      example CoQ(*-)+O(2)-->CoQ+O(2)(*-). However, when K>1, e.g. xanthine oxidase
      forming O(2)(*-), SOD does not affect the steady state-level of H(2)O(2). Thus,
      the current paradigm that SOD will lower the flux of H(2)O(2) does not hold for
      the ETC. These observations indicate that MnSOD contributes to the flux of
      H(2)O(2) in cells and thereby is involved in establishing the cellular redox
      environment and thus the biological state of the cell.

PMID- 17015183
TI  - The mtDNA 15497 G/A polymorphism in cytochrome b in severe obese subjects from
      Southern Italy.
AB  - BACKGROUND AND AIM: A large number of mitochondrial DNA (mtDNA) mutations have
      been implicated in degenerative diseases and aging. The aim of this study was to
      evaluate whether the 15497 G/A mtDNA polymorphism (G251S) in the cytochrome b
      subunit of respiratory complex III, which has been associated with obesity
      related variables and lipid metabolism in a Japanese population, is associated
      with severe obesity also in adult Caucasians from southern Italy. METHODS AND
      RESULTS: Unrelated severely obese patients (n = 317; BMI > 40kg/m2) and controls
      (n = 217; BMI < 25kg/m2) from Southern Italy were genotyped by allelic
      discrimination TaqMan assay for the 15497 G/A mtDNA polymorphism. In obese
      patients fasting serum total cholesterol, triglycerides, HDL-cholesterol and
      glucose were measured enzymatically and sitting blood pressure and heart rate
      were also collected. Mean levels of total cholesterol, triglycerides and glucose
      were below the upper reference limit for healthy subjects. Female obese subjects
      showed lower levels of blood pressure and heart rate and higher levels of HDL
      cholesterol than male obese patients (P < 0.001). All the control subjects and
      315/317 severely obese patients were homozygous for the G allele (wild type),
      whereas only 2/317, were females homozygous for the A allele. CONCLUSIONS: The
      mtDNA 15497 G/A polymorphism in cytochrome b was present in 0.6% obese subjects,
      two females whose lipid parameters and BMI were similar to those of the overall
      group. Therefore, this mutation may appear to contribute in rare instances to
      severe obesity but does not explain the majority of cases in our population. A
      more extensive genetic haplogroup characterization is required to identify
      associations to obesity in Caucasians.

PMID- 17015184
TI  - Effect of two fasting periods of different duration on ghrelin response to a
      mixed meal.
AB  - BACKGROUND AND AIM: The inhibitory effect of food on ghrelin secretion is reduced
      in several eating disorders such as restricting type anorexia nervosa, bulimia
      and obesity. These conditions are frequently characterised by irregular
      distribution of meals during the day. It is unknown whether two short fasting
      periods different duration affect ghrelin response to a mixed meal. Aim of the
      present study was to examine, in healthy volunteers, the effects of two fasting
      periods of different duration on pre- and post-prandial ghrelin concentrations
      after a standard mixed meal. METHODS AND RESULTS: Nine healthy men (mean age+/
      S.E.M., 25.1+/-0.2 years; mean body mass index+/-S.E.M., 22.6+/-0.3kg/m2) were
      studied in 2 days after 12h of fasting (12F) and 17h of fasting (17F) with a
      within-subject repeated measure design. On both days they ate a standardized
      mixed meal. Before each meal hunger rating was evaluated with a visual analogue
      score. Blood samples for ghrelin, insulin, and glucose were collected at 0, 45,
      60, 90, 120, 150 and 180min after meal. Comparing fasting values of 17F with 12F
      there was a significant increase in plasma ghrelin (160+/-20 vs. 146+/-18fmol/mL,
      P=0.015) and hunger rating (evaluated with a visual analogue scores) (7.0+/-0.3
      vs. 5.1+/-0.4, P<0.003). A positive correlation between fasting ghrelin and
      hunger rating (r=0.52, P<0.01) was found. Circulating ghrelin decreased after
      both meals without any significant difference in relation with the previous
      length of fasting. Also postmeal ghrelin AUC as well as fasting and postmeal
      concentrations of insulin and glucose were similar after 12F and 17F.
      CONCLUSIONS: In healthy subjects a longer fasting period increases ghrelin
      concentration but did not affect post-prandial ghrelin response to a mixed meal.

PMID- 17015185
TI  - High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces
      all features of human type 2 diabetic nephropathy: a new rat model of diabetic
      nephropathy.
AB  - BACKGROUND AND AIM: We have developed a new rat model that mimics the natural
      course of diabetic nephropathy seen in type 2 diabetes. METHODS: Nine days after
      intravenous injection of streptozotocin (STZ) (40 mg/kg) or vehicle to 8-week-old
      male Sprague-Dawley rats, the animals' right kidneys were surgically removed. Two
      weeks after surgery, the STZ-injected rats were fed on either a high-fat (ST+HF)
      or a normal (ST) diet, while the vehicle-injected rats were fed on the high-fat
      diet (HF). RESULTS: Baseline biochemical markers did not differ between the three
      groups. Only the ST+HF group showed a significant increase in plasma glucose
      levels after 15 weeks, and simultaneously plasma insulin levels started to
      decrease, followed by an increase in plasma total cholesterol and triglyceride
      levels at 25 weeks and slightly later by an increase in blood pressure. In the
      ST+HF group, significant microalbuminuria was detected at 15 weeks followed by
      overt proteinuria, both of which were absent in the other two groups. Also in
      ST+HF, the creatinine clearance rate increased until week 15, and then gradually
      decreased. Histologically, ST+HF rats showed mesangial expansion at week 25, and
      diffuse glomerular sclerosis at the end of the experiments. CONCLUSION: The
      chronological changes in biochemical, physiological and histological markers in
      ST+HF rats are reminiscent of human type 2 diabetes and nephropathy. Our new
      model of type 2 diabetic nephropathy should help us to understand the
      pathophysiology of the disease and serve to explore measures to prevent and treat
      diabetic nephropathy.

PMID- 17015186
TI  - Early impairment of beta-cell function and insulin sensitivity characterizes
      normotolerant Caucasian women with previous gestational diabetes.
AB  - BACKGROUND AND AIMS: Women with previous gestational diabetes (pGDM) are at high
      risk of developing type 2 diabetes mellitus. The aim of this study was to
      evaluate insulin action and insulin secretion in women with pGDM. METHODS AND
      RESULTS: One hundred and fifty-three pGDM women and 45 with normal glucose
      tolerance during pregnancy (controls) were studied 1-3years after delivery.
      Insulin sensitivity (ISI) and beta-cell secretory capacity (beta-index) were
      derived from 75-g OGTT. Disposition Index was calculated as the product of beta
      index and ISI. One hundred and twenty-two pGDM were normotolerant (NGT) and 31
      had impaired glucose regulation (IGR) i.e. impaired glucose tolerance and/or
      impaired fasting glucose. NGT-pGDM, as compared to controls, had significant
      impairment in insulin action (ISI: 5.46+/-2.81 vs. 7.38+/-3.68, P<0.01) and
      insulin secretion (beta-index: 4.68+/-1.01 vs. 5.24+/-0.82 pmol/min/m(2);
      P<0.01). A further impairment was apparent in IGR-pGDM for beta-index (4.16+/
      1.09; P<0.05). The disposition index was reduced in NGT-pGDM as compared to
      controls (33.9%) and further reduced in IGR-pGDM (28.6%, vs. NGT-pGDM; ANOVA
      P<0.001). In women of normal weight, ISI and beta-index were significantly
      (P<0.01) impaired in NGT-pGDM compared to controls and further reduced in IGR
      pGDM, although a more pronounced defect in insulin secretion was apparent in
      these women (beta-index: 4.02+/-0.9; P<0.05). CONCLUSIONS: Normotolerant women
      with pGDM show both impairment in insulin secretion and action irrespective of
      body weight. A more pronounced defect in insulin secretion seems to characterize
      normal weight women while a more prominent defect in insulin action is found in
      overweight women.

PMID- 17015187
TI  - Metabolic adaptation in the crew of the Hesperides on their Antarctic journey.
AB  - AIMS: We studied the metabolic changes that took place in the crew of the
      Hesperides vessel in their 2001-2002 Antarctic journey, comparing two periods
      differing in diet and physical activity. METHODS AND RESULTS: Lipid profile,
      vitamin and hormone levels were analyzed in 17 subjects who completed the study
      in its two phases. In phase I the participants spent 47 days sailing with hard
      work and rough seas, and the diet was rich in fat and poor in fresh foods. In
      this phase, glucose decreased and HDL-cholesterol, apo-AI, and TSH increased.
      Plasma retinol and alpha-tocopherol levels remained stable, gamma-tocopherol,
      alpha-carotene and beta-carotene significantly decreased, and lycopene
      significantly increased. Phase II lasted 49 days including a 7-day long stop in
      port. This meant that a more varied diet was available and fresh foods were
      present in the hold. There was also less extreme physical activity. The metabolic
      pattern changed direction, glucose rose, HDL-cholesterol and apo-AI decreased and
      the levels of the vitamins that dropped in phase I started to increase. Lycopene
      significantly decreased. CONCLUSION: Contrary to popular beliefs about navigation
      at extreme latitudes, the metabolic changes described may be explained by the
      intense physical activity in a cold environment and a high-fat diet poor in fresh
      products.

PMID- 17015189
TI  - Specific effects of homeopathy: the challenge of explanatory research.

PMID- 17015190
TI  - Outcomes from homeopathic prescribing in medical practice: a prospective,
      research-targeted, pilot study.
AB  - BACKGROUND AND AIMS: A base for targeted research and development in homeopathy
      can be founded on systematic collection and analysis of relevant clinical data
      obtained by doctors in routine practice. With these longer-term aims in mind, we
      conducted a pilot data collection study, in which 14 homeopathic physicians
      collected clinical and outcomes data over a 6-month period in their practice
      setting. METHODS: A specifically designed Excel spreadsheet enabled recording of
      consecutive clinical appointments under the following main headings: date,
      patient identity (anonymised), age and gender, medical condition/complaint
      treated, whether chronic or acute, new or follow-up case, patient-assessed
      outcome (7-point Likert scale: -3 to +3) compared with first appointment,
      homeopathic medicine/s prescribed, whether any other medication/s being taken for
      the condition. Spreadsheets were submitted monthly via email to the project co
      ordinator for data synthesis and analysis. RESULTS: Practitioners typically
      submitted data regularly and punctually, and most data cells were completed as
      required, enabling substantial data analysis. The mean age of patients was 41.5
      years. A total of 1,783 individual patient conditions were treated overall.
      Outcome from two or more homeopathic appointments per patient condition was
      obtained in 961 cases (75.9% positive, 4.6% negative, 14.7% no change; 4.8%
      outcome not recorded). Strongly positive outcomes (scores of +2 or +3) were
      achieved most notably in the frequently treated conditions of anxiety,
      depression, and irritable bowel syndrome. CONCLUSIONS: This multi-practitioner
      pilot study has indicated that systematic recording of clinical data in
      homeopathy is both feasible and capable of informing future research. A refined
      version of the spreadsheet can be employed in larger-scale research-targeted
      clinical data collection in the medical practice setting--particularly in primary
      care.

PMID- 17015191
TI  - Patient compliance with homeopathic therapy.
AB  - The Homeopathic Clinic of the Campo di Marte Hospital, Lucca, Italy (the
      Homeopathic Reference Centre for Tuscany) registered a total of 1287 patients
      seen for the first time between September 1998 and 31 December 2004, of these 560
      (43.5%) returned for a follow-up visit after a minimum interval of 2 months
      following the first consultation. In order to ascertain the reasons for patients
      not returning for follow-up consultations (drop-out) a telephone survey was
      carried out on every patient who had been seen during the period from 1 June 2002
      to 31 May 2003, but had not returned for a follow-up visit. 73/104 eligible
      patients were contacted. 37/73 referred to the effectiveness of the treatment
      which led to an improvement in their state of health, naming this as the reason
      why they did not return for a follow-up visit.

PMID- 17015192
TI  - Evaluation of specific and non-specific effects in homeopathy: feasibility study
      for a randomised trial.
AB  - OBJECTIVE: To determine the feasibility, in terms of acceptability to patients,
      physicians and other staff; data return and statistical power of a study to
      elucidate the relative contributions of specific and non-specific effects in
      homeopathic treatment of dermatitis. DESIGN: Randomised, controlled 4-arm trial,
      2 arms double-blind. SETTING: Outpatient clinic, Royal London Homoeopathic
      Hospital. PARTICIPANTS: Seventy-five adult patients with dermatitis.
      INTERVENTIONS: Patients were randomly allocated to: 'fast track' open verum
      homeopathy, 'fast track' double-blind verum homeopathy, 'fast track' double-blind
      placebo homeopathy or waiting list control. MAIN OUTCOME MEASURES: One hundred
      millimeter visual analogue scale of overall symptom severity; 10 point digital
      scores of sleep, itching, skin condition; weekly 5-point Likert scale of topical
      steroid use; Dermatology Life Quality Index at entry and completion. RESULTS:
      Recruitment was below target, but the study was acceptable to staff and feasible.
      Blinded patients were more likely to withdraw (P=0.021, chi2 test). After
      correction for baseline differences and multiple comparisons, no outcome measure
      showed statistically significant between group differences. Blindness appeared to
      have a negative effect, but this was confounded by differential withdrawal.
      CONCLUSIONS: A definitive trial of this design is unlikely to discriminate the
      relative contributions of the non-specific and specific effects to the outcome of
      homeopathic treatment of dermatitis, because of patient preference issues.

PMID- 17015193
TI  - Effects of homeopathic medications Eupatorium perfoliatum and Arsenicum album on
      parasitemia of Plasmodium berghei-infected mice.
AB  - Malaria is one of the most important parasitic diseases in the world and a major
      public health problem because of emerging drug-resistant strains of Plasmodium. A
      number of synthetic and natural compounds are now being analysed to develop more
      effective antimalarial drugs. We investigated the effect of homeopathic
      preparations of Eupatorium perfoliatum and Arsenicum album on parasitemia using a
      rodent malaria model. We found significant inhibitory effect on parasite
      multiplication with both medications with a level of 60% for Eupatorium
      perfoliatum at a 30 CH potency. Arsenicum album 0/6 gave 70% inhibition but this
      was less stable than Eupatorium perfoliatum. The number of schizonts was higher
      in animals treated with homeopathic medications. Although the mechanism of action
      is unknown, these agents would be good candidates as alternative or complementary
      medications in the treatment of malaria.

PMID- 17015194
TI  - Evidence of the principle of similitude in modern fatal iatrogenic events.
AB  - Samuel Hahnemann attributed fundamental importance to the principle of
      similitude, promoting it to a 'natural law'. Observing that enantiopathic or
      allopathic treatment produced enduring aggravation of the disease symptoms after
      a brief and transitory initial relief, he systematised homeopathic treatment,
      prescribing substances that provoke similar symptoms in healthy individual. Based
      on clinical and experimental observations, he anticipated the concept of
      homeostasis, dividing the effects of substances into: primary action of the
      medicine followed by secondary action or reaction of the organism. This reaction,
      known as the rebound effect or paradoxical action by modern pharmacology, used to
      awake the curative response of the body when the principle of similitude is
      applied, is responsible for several iatrogenic diseases when used on the basis of
      the principle of contraries. This study discusses the role of this paradoxical
      reaction of the organism in the fatal side effects of four important drugs, used
      according to the model of enantiopathic treatment of the symptoms. I present
      evidence relating to acetylsalicylic acid, rofecoxib, antidepressants and long
      acting bronchodilators. The consequences of the allopathic treatment could be
      decreased if health professionals valued homeostasis, minimising the rebound
      effect of the organism by gradual suspension of palliative drugs.

PMID- 17015195
TI  - Heuristics and bias in homeopathy.
AB  - The practice of Homeopathy ought to be strictly logical. In the Organon Samuel
      Hahnemann gives the impression that the unprejudiced observer should be able to
      follow an algorithmic route to the simillimum in every case. Judgement and
      Decision Research, however, indicates that when people grapple with complex
      systems like homeopathy they are more likely to use heuristics or empirical rules
      to help them reach a solution. Thus Hahnemann's concept of the unprejudiced
      observer is virtually impossible to attain. There is inevitable bias in both case
      taking and remedy selection. Understanding the types of bias may enable the
      practitioner to reduce his/her own bias.

PMID- 17015196
TI  - Homoeopathy for the treatment of lichen simplex chronicus: a case series.
AB  - Twenty-seven patients with chronic lichen simplex involving various parts of the
      body were treated. Hydrocotyle was prescribed to 21 patients in different
      potencies (6c, 30c, 200c, 1 M, 10 M), Thuja to three patients (1 M, 10 M),
      Graphites (6c), Kali bich (30c) and Sulphur (200c) to one patient each during 1
      year study period. Only two patients showed complete improvement with Thuja and
      one with Graphites. In other cases, the response was limited to partial relief of
      [corrected] itching.

PMID- 17015197
TI  - 20 years ago: the British Homoeopathic Journal, October 1986.

PMID- 17015199
TI  - The ASBS Bariatric Surgery Centers of Excellence program: a blueprint for quality
      improvement.
AB  - BACKGROUND: Variations in the techniques of bariatric surgery, coupled with the
      lack of a common database, has led to variable and, sometimes negative, outcomes
      from bariatric surgery. Thus, in November 2003, the American Society for
      Bariatric Surgery established Surgical Review Corporation (SRC) as an independent
      nonprofit entity for quality control of bariatric surgery and as a resource for
      data collection and analysis. METHODS: In November 2003, the leadership of the
      American Society for Bariatric Surgery founded SRC as an independent nonprofit
      entity for quality control of bariatric surgery and as resource for research. A
      national set of standards for the Bariatric Surgery Centers of Excellence program
      was developed using a meta-analysis of the relevant published English language
      data, a consensus conference at Georgetown University, and participation by
      stakeholders from industry, third-party payors, and malpractice carriers. A
      software program was developed to provide uniformity in data collection and ease
      of analysis. RESULTS: SRC developed standards that have been accepted by the
      bariatric surgical community and put in place. A system was developed for the
      designation of two levels for the centers, provisional and full. The growth of
      the Centers of Excellence program has been rapid. At present, 135 hospitals and
      265 surgeons have achieved full approval. The centers for Medicare and Medicaid
      Services have recognized the program. On the basis of the reports of 55,567
      patients from the first 176 applicants for full approval and confirmed by SRC
      during site inspections, the 90-day operative mortality rate was 0.35%.
      CONCLUSIONS: The first phase of development has gone well. Future steps include
      the development of a network of bariatric physicians and the development of a
      consortium for research.

PMID- 17015202
TI  - Shared medical appointments: new concept for high-volume follow-up for bariatric
      patients.
AB  - BACKGROUND: Shared medical appointments (SMAs) are a new model in patient care.
      This model was designed to improve patients' access to their physicians and
      improve physician productivity. The aim of this study was to evaluate patient
      satisfaction with SMAs after bariatric surgery. METHODS: The medical records of
      consecutive patients who were followed up after bariatric surgery were
      retrospectively reviewed. The type of bariatric surgery and type of medical
      appointment were recorded, as were the patients' replies to the evaluation
      questionnaires in the SMA group. RESULTS: From April 2004 to December 2004, 277
      individual visits were conducted; 242 visits for patients who underwent Roux-en-Y
      gastric bypass and 35 visits for patients who underwent laparoscopic gastric
      banding. Thirty-three SMAs occurred during that period--28 SMAs for patients who
      underwent Roux-en-Y gastric bypass and 5 SMAs for patients who underwent
      laparoscopic gastric banding. Of the patients who initially participated in an
      SMA, 91% scheduled a subsequent SMA, and 96% indicated that they would recommend
      SMAs to others. On a scale of 1 to 5 (1, poor and 5, excellent), patients graded
      their overall experience with SMAs as 4.5. Other parameters in the questionnaire
      all ranked between 4 and 5. The average waiting period for an appointment before
      the implementation of SMAs was 57.7 days (range 50-65) for new patients and 50
      days (range 20-72) for former patients. After the implementation of SMAs, the
      average waiting period was 25 days (range 8-42) for new patients (P = 0.0046) and
      20.3 days (range 0-42) for former patients (P = 0.06). CONCLUSION: The SMA offers
      the patient prompt access to medical care, enables high-volume follow-up, with
      high satisfaction rates.

PMID- 17015201
TI  - The impact of morbid obesity on the state economy: an initial evaluation.
AB  - BACKGROUND: Obesity's impact on a state's economy has not been fully analyzed.
      This study compared bariatric surgery demographics at a large university hospital
      to that of a broader region's population statistics. From this comparison, an
      economic model was derived that evaluated, for the state of New Mexico, the cost
      of obesity in terms of lost business output, employment, and income. METHODS:
      Between September 2003 and September 2005, we analyzed the charts of all of our
      patients from New Mexico who underwent laparoscopic gastric bypass and
      laparoscopic banding. Input-output analysis estimate margins, the purchase prices
      for goods and services, and regional purchase coefficients, the percent of
      spending by local suppliers, were used to model the regional economy. Collected
      patient data, used in conjunction with IMPLAN model data, were used to estimate,
      on a regional basis, an industry-by-industry formulation of input-output accounts
      to calculate multipliers in order to assess the impact of economic costs of the
      obese on the general economy. RESULTS: Total labor income impacts are nearly 200
      million dollars, 1,660 dollars of output income per household and 245 dollars of
      labor income per household. Obesity cost New Mexico more than 7,300 jobs and cut
      state and local tax revenues by more than 48 million dollars. CONCLUSION:
      Obesity's impact of more than 1.3 billion dollars amounts to 2.5% of New Mexico's
      gross state product. Governmental measures to combat this menace are warranted.

PMID- 17015203
TI  - Centers of Excellence in Bariatric Surgery: design, implementation, and one-year
      outcomes.
AB  - BACKGROUND: Bariatric surgery procedures increased from <20,000 annually in the
      early 1990s to >100,000 in 2003. The complications related to surgery have
      increased disproportionately, causing some payers to discontinue coverage for
      bariatric procedures and reducing patient access to an effective treatment
      modality. This report describes an alternative approach-the creation of a network
      of Centers of Excellence (COE) in Bariatric Surgery. METHODS: Blue Cross and Blue
      Shield of North Carolina developed a COE program by working collaboratively with
      the bariatric surgery community. Through systematic review, the collaborative
      identified bariatric surgical programs that appropriately select patients,
      comprehensively evaluate and prepare patients for surgery, produce superior
      outcomes, and provide long-term follow-up for patients. RESULTS: Seven practices
      were selected as Blue Cross and Blue Shield of North Carolina Bariatric Surgery
      COE. The short-term results comparing the 12 months before COE implementation and
      the 12 months after implementation included a 14% decline in the number of
      bariatric procedures performed (693 versus 596), a 23% decrease in the number of
      surgeons billing for bariatric procedures (53 versus 41), a 30-day readmission
      rate of 4.7% for COE providers and 8.3% for non-COE providers, and an average
      inpatient length of stay of 2.5 days for COE providers and 3.0 days for non-COE
      providers. The proportion of procedures performed by the COE providers increased
      from 55% to 61%. CONCLUSION: The preliminary results are encouraging, with COE
      providers demonstrating reduced 30-day readmission rates and, surprisingly,
      overall reductions in the rate and number of procedures performed and the number
      of physicians performing them.

PMID- 17015204
TI  - Laparoscopic adjustable gastric banding for patients with body mass index of
      <or=35 kg/m2.
AB  - BACKGROUND: Many mild-to-moderately obese individuals (body mass index [BMI] 30
      35 kg/m(2)) have serious diseases related to their obesity. Nonoperative therapy
      is ineffective in the long term, yet surgery has never been made widely available
      to this population. METHODS: Between 1996 and 2004, 93 patients with a BMI of 30
      35 kg/m(2) underwent laparoscopic adjustable gastric banding with the LAP-BAND.
      All patients were referred by their primary physician, entered into a
      comprehensive bariatric surgery program at one Australian center, and operated on
      by one surgeon. Data on all patients were collected prospectively and entered
      into an electronic registry. The study parameters included preoperative age,
      gender, BMI, presence of co-morbidities, percentage of excess weight loss, and
      resolution of co-morbidities. RESULTS: The mean age was 44.6 years (range 16-76),
      mean weight was 98 kg, and the mean BMI was 32.7 kg/m(2) (range 30-34). Of the 93
      patients, 42 (45%) had co-morbidities, including asthma, diabetes, hypertension,
      and sleep apnea. The proportion of patients in follow-up was 79%, 85%, and 89% at
      1, 2, and 3 years, respectively. The mean weight was reduced to 71 kg at 1 year,
      72 kg at 2 years, and 72 kg at 3 years. The mean BMI was reduced to 27.2 +/- 2.2,
      27.3 +/- 3.1, and 27.6 +/- 3.7 kg/m(2), respectively, and the mean percentage of
      excess weight loss was 57.9% +/- 24.5%, 57.6 +/- 29.3%, and 53.8% +/- 32.8% at 1,
      2, and 3 years, respectively. At 3 years, the BMI was 18-24 kg/m(2) in 34%, 25-29
      kg/m(2) in 51%, and 30-35 kg/m(2) in 10%. At 3 years, the percentage of excess
      weight loss was <25% in 10%, 25-50% in 24%, 50-75% in 51%, and >75% in 10%. The
      co-morbidities improved or completely resolved in most patients. No mortality
      occurred. CONCLUSION: We are very encouraged by this series of low BMI patients
      treated with the LAP-BAND. Their weight loss has been good, the complications
      have been minimal, and the co-morbidities have partially or wholly resolved. With
      additional study, it is reasonable to expect the weight guidelines for bariatric
      surgery to be altered to include patients with a BMI of 30-35 kg/m(2).

PMID- 17015205
TI  - Errant and unrecognized antiperistaltic Roux limb construction during Roux-en-Y
      gastric bypass for clinically significant obesity.
AB  - BACKGROUND: Proper isoperistaltic orientation of the Roux limb is important. We
      report on 5 patients with errant anatomic construction of the Roux limb during
      Roux-en-Y gastric bypass for clinically significant obesity. METHODS: We
      performed a retrospective review of the medical records of these 5 patients. Of
      the 5 patients, 3 had undergone open and 2 laparoscopic Roux-en-Y gastric bypass.
      RESULTS: These 5 patients developed persistent and predominantly bilious vomiting
      in the immediate postoperative period, with subsequent protein-calorie
      malnutrition. At least 18 operations were undertaken in these 5 patients at
      different times to correct the abnormally dilated Roux limb to no avail. The
      diagnosis of an antiperistaltic anatomy was unsuspected, and these operations
      failed to address the errant anatomy of the Roux limb or resolve the symptoms.
      Definitive treatment involved repositioning of the Roux limb in an isoperistaltic
      direction, which resulted in immediate resolution of the symptoms and reversal of
      the protein-calorie malnutrition. CONCLUSION: Antiperistaltic Roux anatomy is
      deleterious, and repositioning of the Roux limb in an isoperistaltic direction
      will resolve the symptoms and associated protein-calorie malnutrition.

PMID- 17015206
TI  - Laparoscopic resection of gastric diverticulum presenting after Roux-en-Y gastric
      bypass.
AB  - Gastric diverticula are extremely rare and may be congenital or acquired.
      Postgastrectomy formation of gastric diverticula has been attributed to
      outpouching through the weakened wall of the stomach. When symptomatic, gastric
      diverticula may cause pain, nausea, dysphagia, and vomiting. Gastric diverticula
      may also be associated with ectopic mucosa, ulcers, and neoplastic changes. We
      report a case of gastric cardia diverticulum that became symptomatic after
      laparoscopic Roux-en-Y gastric bypass. The patient was successfully treated with
      laparoscopic resection.

PMID- 17015207
TI  - Erosion of gastric pacemaker lead into small bowel.

PMID- 17015208
TI  - Gastropericardial fistula after Roux-en-Y gastric bypass: a case report.

PMID- 17015209
TI  - Unusual case of gastric bezoar causing obstruction after Roux-en-Y gastric
      bypass.

PMID- 17015211
TI  - The Swedish Obese Subjects Study--what has been accomplished to date?

PMID- 17015210
TI  - Does ghrelin really matter after bariatric surgery?

PMID- 17015212
TI  - Swedish Obese Subjects study--best available data to support antiobesity surgery?

PMID- 17015213
TI  - Studies show reduction in mortality after bariatric surgery.

PMID- 17015214
TI  - Can't we all get along? The need to unify our efforts at bariatric surgery center
      accreditation.

PMID- 17015215
TI  - Yes, we can all get along: American College of Surgeons' response to editorial.

PMID- 17015216
TI  - Our door is open.

PMID- 17015217
TI  - Self-expandable metal stents to treat gastric leaks.
AB  - OBJECTIVES: Anastomotic leak is a major complication after gastric bypass (GBP)
      surgery, and it usually necessitates reoperation and is associated with long-term
      recovery and death. We present our experience with the use of self-expandable
      metal stents (SEMS) to treat this complication. METHODS: Seventeen patients (14
      males and 3 females, mean body mass index of 43.7 kg/m(2)) with gastro-jejunal
      leak after GBP underwent covered SEMS placement 1 to 3 weeks after surgery: 8
      laparoscopic, 5 open, and 4 revisional procedures. All patients who underwent
      laparoscopic and revisional procedures had abdominal drains placed at surgery. No
      drains were placed in the open cases. Five patients required surgery to drain an
      abdominal abscess. RESULTS: Tolerance for oral feeding was achieved between 2 and
      3 days after SEMS placement. One patient persisted with a minimal leak for 2
      weeks. To date, all stents have been removed endoscopically 3.2 +/- 1.2 months
      after placement. Four patients needed a second session to complete removal of the
      uncovered top of the stent. Two esophageal mucosal tears occurred; both were
      managed conservatively. Sixteen patients had a totally sealed leak. One remained
      with a gastro-gastric fistula. One stent spontaneously migrated to the splenic
      flexure and was removed colonoscopically. CONCLUSIONS: SEMS placement for gastro
      jejunal leaks is a safe therapeutic option.

PMID- 17015219
TI  - Regarding comments made on Cohen R, Pinheiro JS, Correa J, Schiavon CA.
      Laparoscopic Roux-en-Y gastric bypass for BMI <35 kg/m(2): a tailored approach.
      Surg Obes Relat Dis 2006;2:401-4.

PMID- 17015220
TI  - Frequency and management of internal hernias after laparoscopic antecolic
      antegastric Roux-en-Y gastric bypass without division of the small bowel
      mesentery or closure of mesenteric defects: review of 1400 consecutive cases.

PMID- 17015221
TI  - Liver cirrhosis and bariatric operations.

PMID- 17015223
TI  - A hundred years of Alzheimer's disease research.
AB  - On the 100th anniversary of Alzheimer's lecture describing the
      clinicopathological entity which bears his eponym, this article reviews the major
      areas of progress in our understanding of the disease and outlines the many gaps
      still remaining. The progress toward effective mechanistic therapy is reviewed.

PMID- 17015225
TI  - Mechanisms of Parkinson's disease linked to pathological alpha-synuclein: new
      targets for drug discovery.
AB  - Classic Parkinson's disease (PD) is characterized by fibrillar alpha-synuclein
      inclusions known as Lewy bodies in the substantia nigra, which are associated
      with nigrostriatal degeneration. However, alpha-synuclein pathologies accumulate
      throughout the CNS in areas that also undergo progressive neurodegeneration,
      leading to dementia and other behavioral impairments in addition to parkinsonism.
      Although mutations in the alpha-synuclein gene only cause Lewy body PD in rare
      families, and although there are multiple other, albeit rare, genetic causes of
      familial parkinsonism, sporadic Lewy body PD is the most common movement
      disorder, and insights into mechanisms underlying alpha-synuclein-mediated
      neurodegeneration provide novel targets for the discovery of disease-modifying
      therapies for PD and related neurodegenerative alpha-synucleinopathies.

PMID- 17015226
TI  - ALS: a disease of motor neurons and their nonneuronal neighbors.
AB  - Amyotrophic lateral sclerosis is a late-onset progressive neurodegenerative
      disease affecting motor neurons. The etiology of most ALS cases remains unknown,
      but 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1).
      Since sporadic and familial ALS affects the same neurons with similar pathology,
      it is hoped that therapies effective in mutant SOD1 models will translate to
      sporadic ALS. Mutant SOD1 induces non-cell-autonomous motor neuron killing by an
      unknown gain of toxicity. Selective vulnerability of motor neurons likely arises
      from a combination of several mechanisms, including protein misfolding,
      mitochondrial dysfunction, oxidative damage, defective axonal transport,
      excitotoxicity, insufficient growth factor signaling, and inflammation. Damage
      within motor neurons is enhanced by damage incurred by nonneuronal neighboring
      cells, via an inflammatory response that accelerates disease progression. These
      findings validate therapeutic approaches aimed at nonneuronal cells.

PMID- 17015224
TI  - Sorting through the cell biology of Alzheimer's disease: intracellular pathways
      to pathogenesis.
AB  - During the first 100 years of Alzheimer's disease research, this devastating and
      intractable disorder has been characterized at the clinical, histological, and
      molecular levels. Nevertheless, many key mechanistic questions remain unanswered.
      Here we will emphasize the importance of the cell biology of Alzheimer's disease,
      reviewing the relevant literature that has expanded our mechanistic
      understanding, with a particular focus on pathways regulating protein sorting.
      Accumulated evidence indicates that sorting pathways may be uniquely vulnerable
      to disease pathogenesis, and recent studies have begun to reveal disease-related
      defects in the regulation of protein sorting.

PMID- 17015227
TI  - The neurobiology of multiple sclerosis: genes, inflammation, and
      neurodegeneration.
AB  - The autoimmune model of multiple sclerosis (MS) pathogenesis provided for many
      years a useful but incomplete conceptual framework for understanding the complex
      array of factors that lead to the loss of immune homeostasis, myelin and axonal
      injury, and progressive neurological symptoms. The availability of novel tools in
      molecular neurogenetics and increasingly sophisticated neuroimaging technologies,
      together with the revitalization of MS neuropathology, has created a new paradigm
      for the multidisciplinary study of this disease. This is reflected by the growing
      resolution of the MS genomic map, discovery of delicate inflammatory networks
      that are perturbed in MS, identification of mediators of demyelination, and
      recognition that cumulative axonal loss and neuronal injury are the histological
      correlates of neurological disability. Together, these advances have set the
      stage for the development of therapeutic approaches designed to target the
      demyelinating and neurodegenerative components of the disease and promote repair.

PMID- 17015229
TI  - Splicing regulation in neurologic disease.
AB  - The importance of alternative splicing in the regulation of diverse biological
      processes is reflected in the growing list of human diseases associated with
      known or suspected splicing defects. It is becoming evident that alternative
      splicing plays a particularly important role in neurologic disease, which is
      perhaps not surprising given the important role splicing plays in generating
      complexity and function in the brain. This review considers the evidence that
      defects in regulation of splicing may underlie many types of human neurologic
      diseases.

PMID- 17015230
TI  - Genomic rearrangements and gene copy-number alterations as a cause of nervous
      system disorders.
AB  - Genomic disorders are a group of human genetic diseases caused by genomic
      rearrangements resulting in copy-number variation (CNV) affecting a dosage
      sensitive gene or genes critical for normal development or maintenance. These
      disorders represent a wide range of clinically distinct entities but include many
      diseases affecting nervous system function. Herein, we review selected
      neurodevelopmental, neurodegenerative, and psychiatric disorders either known or
      suggested to be caused by genomic rearrangement and CNV. Further, we emphasize
      the cause-and-effect relationship between gene CNV and complex disease traits. We
      also discuss the prevalence and heritability of CNV, the correlation between CNV
      and higher-order genome architecture, and the heritability of personality,
      behavioral, and psychiatric traits. We speculate that CNV could underlie a
      significant proportion of normal human variation including differences in
      cognitive, behavioral, and psychological features.

PMID- 17015228
TI  - Mechanisms of neuropathic pain.
AB  - Neuropathic pain refers to pain that originates from pathology of the nervous
      system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma,
      "channelopathies," and autoimmune disease are examples of diseases that may cause
      neuropathic pain. The development of both animal models and newer pharmacological
      strategies has led to an explosion of interest in the underlying mechanisms.
      Neuropathic pain reflects both peripheral and central sensitization mechanisms.
      Abnormal signals arise not only from injured axons but also from the intact
      nociceptors that share the innervation territory of the injured nerve. This
      review focuses on how both human studies and animal models are helping to
      elucidate the mechanisms underlying these surprisingly common disorders. The
      rapid gain in knowledge about abnormal signaling promises breakthroughs in the
      treatment of these often debilitating disorders.

PMID- 17015231
TI  - Autoimmune channelopathies and related neurological disorders.
AB  - Ion channels are crucial elements in neuronal signaling and synaptic
      transmission, and defects in their function are known to underlie rare genetic
      disorders, including some forms of epilepsy. A second class of channelopathies,
      characterized by autoantibodies against ligand- and voltage-gated ion channels,
      cause a variety of defects in peripheral neuromuscular and ganglionic
      transmission. There is also emerging evidence for autoantibody-mediated
      mechanisms in subgroups of patients with central nervous system disorders,
      particularly those involving defects in cognition or sleep and often associated
      with epilepsy. In all autoimmune channelopathies, the relationship between
      autoantibody specificity and clinical phenotype is complex. But with this new
      information, autoimmune channelopathies are detected and treated with increasing
      success, and future research promises new insights into the mechanisms of
      dysfunction at neuronal synapses and the determinants of clinical phenotype.

PMID- 17015232
TI  - Neurobiology of schizophrenia.
AB  - With its hallucinations, delusions, thought disorder, and cognitive deficits,
      schizophrenia affects the most basic human processes of perception, emotion, and
      judgment. Evidence increasingly suggests that schizophrenia is a subtle disorder
      of brain development and plasticity. Genetic studies are beginning to identify
      proteins of candidate genetic risk factors for schizophrenia, including
      dysbindin, neuregulin 1, DAOA, COMT, and DISC1, and neurobiological studies of
      the normal and variant forms of these genes are now well justified. We suggest
      that DISC1 may offer especially valuable insights. Mechanistic studies of the
      properties of these candidate genes and their protein products should clarify the
      molecular, cellular, and systems-level pathogenesis of schizophrenia. This can
      help redefine the schizophrenia phenotype and shed light on the relationship
      between schizophrenia and other major psychiatric disorders. Understanding these
      basic pathologic processes may yield novel targets for the development of more
      effective treatments.

PMID- 17015233
TI  - Neural synchrony in brain disorders: relevance for cognitive dysfunctions and
      pathophysiology.
AB  - Following the discovery of context-dependent synchronization of oscillatory
      neuronal responses in the visual system, novel methods of time series analysis
      have been developed for the examination of task- and performance-related
      oscillatory activity and its synchronization. Studies employing these advanced
      techniques revealed that synchronization of oscillatory responses in the beta-
      and gamma-band is involved in a variety of cognitive functions, such as
      perceptual grouping, attention-dependent stimulus selection, routing of signals
      across distributed cortical networks, sensory-motor integration, working memory,
      and perceptual awareness. Here, we review evidence that certain brain disorders,
      such as schizophrenia, epilepsy, autism, Alzheimer's disease, and Parkinson's are
      associated with abnormal neural synchronization. The data suggest close
      correlations between abnormalities in neuronal synchronization and cognitive
      dysfunctions, emphasizing the importance of temporal coordination. Thus, focused
      search for abnormalities in temporal patterning may be of considerable clinical
      relevance.

PMID- 17015234
TI  - Drosophila in the study of neurodegenerative disease.
AB  - As populations benefit from increasing lifespans, neurodegenerative diseases have
      emerged as a critical health concern. How can the fruit fly, Drosophila
      melanogaster, contribute to curing human diseases of the nervous system? A
      growing number of neurodegenerative diseases, as well as other human diseases,
      are being modeled in Drosophila and used as a platform to identify and validate
      cellular pathways that contribute to neurodegeneration and to identify promising
      therapeutic targets by using a variety of approaches from screens to target
      validation. The unique properties and tools available in the Drosophila system,
      coupled with the fact that testing in vivo has proven highly productive, have
      accelerated the progress of testing therapeutic strategies in mice and,
      ultimately, humans. This review highlights selected recent applications to
      illustrate the use of Drosophila in studying neurodegenerative diseases.

PMID- 17015235
TI  - Modeling madness in mice: one piece at a time.
AB  - Mouse models that recapitulate the full phenotypic spectrum of a psychiatric
      disorder, such as schizophrenia, are impossible. However, a more piecemeal
      recreation of phenotypic components is feasible and promises to harness the power
      of animal models using approaches that are either off limits or confounded by
      drug treatment in humans. In that context, animal models will have a central and
      indispensable role in the process of discovering the causes of psychiatric
      disorders and generating novel, mechanism-based treatments. Here, we discuss
      current approaches used to generate animal models of psychiatric disorders,
      address the different components of these disorders that can be modeled in
      animals, and describe currently available analytical tools. We also discuss
      accumulating empirical data and take an in-depth look at what we believe to be
      the future of animal models made possible by recent advances in psychiatric
      genetics.

PMID- 17015236
TI  - Deep brain stimulation for neurologic and neuropsychiatric disorders.
AB  - In the 1960s, ablative stereotactic surgery was employed for a variety of
      movement disorders and psychiatric conditions. Although largely abandoned in the
      1970s because of highly effective drugs, such as levodopa for Parkinson's disease
      (PD), and a reaction against psychosurgery, the field has undergone a virtual
      renaissance, guided by a better understanding of brain circuitry and the circuit
      abnormalities underlying movement disorders such as PD and neuropsychiatric
      conditions, such as obsessive compulsive disorder. High-frequency electrical deep
      brain stimulation (DBS) of specific targets, introduced in the early 1990s for
      tremor, has gained widespread acceptance because of its less invasive,
      reversible, and adjustable features and is now utilized for an increasing number
      of brain disorders. This review summarizes the rationale behind DBS and the use
      of this technique for a variety of movement disorders and neuropsychiatric
      diseases.

PMID- 17015237
TI  - Brain-controlled interfaces: movement restoration with neural prosthetics.
AB  - Brain-controlled interfaces are devices that capture brain transmissions involved
      in a subject's intention to act, with the potential to restore communication and
      movement to those who are immobilized. Current devices record electrical activity
      from the scalp, on the surface of the brain, and within the cerebral cortex.
      These signals are being translated to command signals driving prosthetic limbs
      and computer displays. Somatosensory feedback is being added to this control as
      generated behaviors become more complex. New technology to engineer the tissue
      electrode interface, electrode design, and extraction algorithms to transform the
      recorded signal to movement will help translate exciting laboratory
      demonstrations to patient practice in the near future.

PMID- 17015238
TI  - Diffusion-weighted magnetic resonance imaging and its application to cancer.
AB  - Diffusion-weighted magnetic resonance imaging (DW-MRI) provides image contrast
      through measurement of the diffusion properties of water within tissues.
      Application of diffusion sensitising gradients to the MR pulse sequence allows
      water molecular displacement over distances of 1-20 microm to be recognised.
      Diffusion can be predominantly unidirectional (anisotropic) or not (isotropic).
      Combining images obtained with different amounts of diffusion weighting provides
      an apparent diffusion coefficient (ADC) map. In cancer imaging DW-MRI has been
      used to distinguish brain tumours from peritumoural oedema. It is also
      increasingly exploited to differentiate benign and malignant lesions in liver,
      breast and prostate where increased cellularity of malignant lesions restricts
      water motion in a reduced extracellular space. It is proving valuable in
      monitoring treatment where changes due to cell swelling and apoptosis are
      measurable as changes in ADC at an earlier stage than subsequent conventional
      radiological response indicators.

PMID- 17015239
TI  - Contrast-enhanced ultrasound for examining tumor biology.
AB  - This paper reviews the potential of ultrasound for assessing the viability and
      biological behavior of tumors. Unlike color Doppler sonography, modern techniques
      for contrast-enhanced ultrasound permit the measurement of tissue perfusion
      irrespective of vessel size or flow velocity. Perfusion can also be assessed
      quantitatively, using replenishment kinetics or derivates thereof. The perfusion
      of tumors is a surrogate parameter of their viability and may mirror their
      response to therapy. Furthermore, the degree of vascularity in a tumor may
      express its aggressiveness and help to predict its response to treatment. In
      animal models, a decrease in blood flow has been shown to precede a shrinkage of
      tumors treated with anti-angiogenic compounds. In liver metastases, arterial and
      portal blood supply can be assessed separately, and a response to stereotactic
      radiotherapy was found to go along with a decrease in arterial perfusion.
      Moreover, a relatively high arterial perfusion of liver metastases may predict a
      response to chemotherapy. Contrast-enhanced ultrasound may be a potent tool for
      assessing the effects of anti-angiogenic treatment in patients.

PMID- 17015240
TI  - Before first sex: gender differences in emotional relationships and physical
      behaviors among adolescents in the Philippines.
AB  - CONTEXT: Early age at first sex has been identified as a risk factor for
      unplanned pregnancy and HIV infection. However, the emotional relationships and
      physical behaviors that precede first intercourse, and how they differ by sex,
      also may provide important cues about how to prevent sexual risk behavior.
      METHODS: The precoital activities of 2,051 adolescents aged 17-19 in Cebu,
      Philippines, are examined using 1998-2000 and 2002 data from the Cebu
      Longitudinal Health and Nutrition Survey. The timing and tempo of emotional
      relationships and physical behaviors for males and females are described. Cox
      proportional hazards models are used to identify the characteristics associated
      with age at first sex. RESULTS: Males engage in precoital physical behaviors and
      first sex at younger ages than females. Although the standard order in which the
      two sexes engage in emotional relationships for the first time is the same, males
      progress through the sequence more quickly than females. After adolescents have
      progressed through the sequence of emotional relationships, there is a gap of a
      least a year before they begin to have sex. In the multivariate analysis, rapid
      progression through the sequence of emotional relationships was associated with
      initiating sex at a younger age for females (hazard ratio, 1.5), but not for
      males. CONCLUSION: The period between first date and first sex experienced by
      both males and females provides an opportunity to ensure that adolescents have
      access to the information and services that will allow them to make informed
      choices about sexual behavior.

PMID- 17015241
TI  - Maternal and social factors associated with abortion in India: a population-based
      study.
AB  - CONTEXT: A cultural preference for sons may be a factor driving recourse to
      abortion in India, as women carrying female fetuses may decide to terminate their
      pregnancies. To assess this hypothesis, more information on the incidence of
      abortion, and on maternal and social correlates of the procedure, is needed.
      METHODS: Birth order-specific abortion ratios were calculated using the birth
      histories of 90,303 ever-married women aged 15-49 who participated in India's
      1998-1999 National Family Health Survey. For the first four births, the
      association between abortion and various maternal and social variables, including
      the sex of the respondent's last child, was assessed using logistic regression.
      RESULTS: The overall abortion ratio was 17.0 per 1,000 pregnancies. The ratio
      increased from 5.3 per 1,000 pregnancies for first-order births to 25.8 per 1,000
      pregnancies for third-order births and then declined. The strongest predictor of
      abortion was maternal education: Women with at least a primary education were
      more likely than those with no education to have had an abortion (odds ratios,
      1.9-6.7). Rural residence was associated with a reduced likelihood of abortion
      (0.6). There was no association between the sex of a woman's previous child and
      the odds that she subsequently had an abortion. CONCLUSION: At the national
      level, it is likely that unintended pregnancy, rather than the sex of the
      previous child, underlies demand for abortion in India. Rising educational
      attainment among women may lead to an increase in the demand for abortion.

PMID- 17015242
TI  - Sexual initiation, substance use, and sexual behavior and knowledge among
      vocational students in northern Thailand.
AB  - CONTEXT: Thailand has undergone dramatic social changes in the last two decades,
      yet little is known about factors related to sexual initiation among adolescents.
      METHODS: A survey using the audio computer-assisted self-interviewing method was
      conducted to assess social and demographic characteristics, substance use, sexual
      behavior, and knowledge of HIV and STIs among 1,725 vocational school students
      aged 15-21 living in northern Thailand. Gender differences for these factors were
      evaluated using chi-square and Mann-Whitney U tests. Multivariate survival
      analysis using Cox proportional hazards models assessed associations between
      these variables and sexual initiation for each gender. RESULTS: Males initiated
      sexual intercourse at an earlier age than females (median ages of 17 and 18,
      respectively). At any given age, sexual initiation was associated with having a
      nonagricultural background and using alcohol or methamphetamine (adjusted rate
      ratios, 1.3-2.9). For males, initiation was also associated with having parents
      who did not live together, having a friend as a confidant, tobacco use, high
      perceived risk for HIV and high STI knowledge (1.3-1.7). For females, other
      factors associated with earlier initiation were younger age at interview, living
      away from family, lacking a family member as a confidant, high perceived risk for
      STIs and ever having smoked marijuana (1.3-2.4). CONCLUSIONS: Interventions to
      ameliorate the adverse consequences of early sexual initiation need to address
      social influences such as parents and peer groups. Programs should identify and
      target high-risk subgroups, such as those who are sexually experienced at an
      early age and those engaged in patterns of generalized risk-taking.

PMID- 17015243
TI  - Induced abortion and unintended pregnancy in Guatemala.
AB  - CONTEXT: Although Guatemalan law permits induced abortion only to save a woman's
      life, many women obtain abortions, often under unsafe conditions and in response
      to an unintended pregnancy. Recent studies indicate that unsafe abortion is a key
      factor contributing to maternal morbidity and mortality in the country, but no
      national data on the incidence of abortion exist. METHODS: Surveys of all
      hospitals that treat women for postabortion complications and of 74 professionals
      who are knowledgeable about the conditions of abortion provision in Guatemala
      were conducted in 2003. Indirect estimation techniques were used to calculate the
      number of induced abortions performed annually. Abortion rates and ratios and the
      level of unintended pregnancy were calculated for the nation and its eight
      regions. RESULTS: Nearly 65,000 induced abortions are performed annually in
      Guatemala, and about 21,600 women are hospitalized for treatment of
      complications. Abortions occur at a rate of 24 per 1,000 women aged 15-49, and
      there is one abortion for every six births. The abortion rate is higher than
      average in the Southwest (less developed, mainly indigenous population) and
      Metropolitan (more developed, mainly nonindigenous population) regions (29-30 per
      1,000 women). Over a quarter of all births are unplanned; combining unplanned
      births with abortions yields estimates that 32% of pregnancies in Guatemala are
      unintended, with an unintended pregnancy rate of 66 per 1,000 women. CONCLUSIONS:
      Unsafe abortion has a significant impact on women's health in Guatemala.
      Comprehensive government programs are needed to address the issues of unintended
      pregnancy and unsafe abortion, with attention to regional differences.

PMID- 17015244
TI  - Internal migration and contraceptive knowledge and use in Guatemala.
AB  - CONTEXT: Levels of modern contraceptive knowledge and use among people living in
      rural areas of Guatemala differ substantially from those of people living in
      urban areas. Understanding the pace and extent of rural-to-urban migrants'
      adoption of urban contraceptive practices is important in determining if there is
      a strong need for migrant-focused reproductive health programs. METHODS:
      Bivariate and multivariate analyses of data on 971 married male and female
      respondents in the 1999 Guatemalan Migration and Reproductive Health Survey were
      used to examine how migration status and duration of residence in an urban area
      are associated with knowledge of modern contraceptive methods and current
      contraceptive use. RESULTS: Migrants' contraceptive knowledge was positively
      associated with the number of years they had lived in an urban area. Mayan
      migrants in Guatemala City did not accumulate contraceptive knowledge at the same
      rate as non-Mayan migrants, perhaps due to cultural and linguistic barriers to
      obtaining knowledge of and access to contraceptives. Rural-to-urban migrants
      eventually achieve a level of modern contraceptive use slightly below that of
      urban nonmigrants, with the level of contraceptive knowledge being an important
      factor associated with use of modern methods. CONCLUSIONS: Migrants possess
      limited knowledge of modern contraceptive methods and, therefore, may experience
      unmet need for contraception or may have a limited choice of modern contraceptive
      methods during their first years in an urban destination. Programs designed to
      raise contraceptive awareness and use should target recent migrants--particularly
      indigenous Mayans--in urban areas.

PMID- 17015246
TI  - Anthocyanins: structural characteristics that result in unique metabolic patterns
      and biological activities.
AB  - Interest in anthocyanins has increased immensely during the past decade. From
      these studies, it is clear that anthocyanins have unique properties: Anthocyanins
      are absorbed intact and absorption can be saturated; acylation of anthocyanins
      lowers their apparent absorption; anthocyanidin diglycosides in the form of
      sambubioside or rutinoside impart increased stability to the anthocyanin
      molecule; and the quantities excreted in urine are less than 0.1% of intake.
      However, 60-90% of the anthocyanins may disappear from the gastrointestinal tract
      within 4 h after a meal. What happens to the bulk of the anthocyanins that
      disappear is not clear. Degradation accounts for a part of this disappearance,
      but differs for the various aglycones and may be modified further by the nature
      of the aglycone glycosylation, which further complicates our understanding of
      this process. Anthocyanins may play an important role in health promotion in
      terms of obesity prevention, cardiovascular health, anti-inflammatory and anti
      cancer effects.

PMID- 17015247
TI  - (+)-Catechin is more bioavailable than (-)-catechin: relevance to the
      bioavailability of catechin from cocoa.
AB  - Catechin is a flavonoid present in fruits, wine and cocoa products. Most foods
      contain the (+)-enantiomer of catechin but chocolate mainly contains ( - )
      catechin, in addition to its major flavanol, ( - )-epicatechin. Previous studies
      have shown poor bioavailability of catechin when consumed in chocolate. We
      compared the absorption of ( - ) and (+)-catechin after in situ perfusion of 10,
      30 or 50 micromol/l of each catechin enantiomer in the jejunum and ileum in the
      rat. We also assayed 23 samples of chocolate for (+) and ( - )-catechin. Samples
      were analyzed using HPLC with a Cyclobond I-2000 RSP chiral column. At all
      concentrations studied, the intestinal absorption of ( - )-catechin was lower
      than the intestinal absorption of (+)-catechin (p < 0.01). Plasma concentrations
      of ( - )-catechin were significantly reduced compared to (+)-catechin (p < 0.05).
      The mean concentration of ( - )-catechin in chocolate was 218 +/- 126 mg/kg
      compared to 25 +/- 15 mg/kg (+)-catechin. Our findings provide an explanation for
      the poor bioavailability of catechin when consumed in chocolate or other cocoa
      containing products.

PMID- 17015248
TI  - The relative contribution of the small and large intestine to the absorption and
      metabolism of rutin in man.
AB  - Tomato juice containing rutin (quercetin-3-rutinoside) was ingested by healthy
      volunteers and ileostomists. Blood and urine collected over 24 h were analysed by
      HPLC with photodiode array (PDA) and tandem mass spectrometric detection. Low
      concentrations of isorhamnetin-3-glucuronide (Cmax = 4.3 +/- 1.5 nmoles/l) and
      quercetin-3-glucuronide (Cmax = 12 +/- 2 nmoles/l) were detected in plasma of
      healthy subjects. Metabolites appeared in blood after 4 h indicating absorption
      from the large intestine. Nine metabolites of rutin were detected in urine but
      with considerable variation in total amount (40 +/- 1-4981 +/- 115 nmoles over 24
      h). No metabolites were detected in plasma or urine of ileostomists and 86 +/- 3%
      of the ingested rutin was recovered in ileal fluid. In subjects with an intact
      large intestine, but not ileostomists, rutin was catabolised with the appearance
      of 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 3
      hydroxyphenylacetic acid in urine accounting for 22% of rutin intake.

PMID- 17015249
TI  - Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid
      hydroperoxide-dependent formation of reactive oxygen species in differentiated PC
      12 cells.
AB  - To assess the efficacy of conjugated quercetin metabolites as attenuators for
      oxidative stress in the central nervous system, we measured the 13
      hydroperoxyoctadecadienoic acid (13-HPODE)-dependent formation of reactive oxygen
      species (ROS) in pheochromocytoma PC-12 cells in the presence of quercetin 3-O
      beta-glucuronide (Q3GA) and related compounds. A 2',7'-dichlorofluorescin (DCFH)
      assay showed that Q3GA significantly suppressed the formation of ROS, when it was
      coincubated with 13-HPODE (coincubation system). However, it was less effective
      than quercetin aglycon in the concentration range from 0.5 to 10 microM. In an
      experiment in which the cells were incubated with the test compounds for 24 h
      before being exposed to 13-HPODE, Q3GA was also effective in suppressing the
      formation of ROS in spite that little Q3GA was taken up into the cells. These
      results suggest that antioxidative metabolites of quercetin are capable of
      protecting nerve cells from attack of lipid hydroperoxides.

PMID- 17015250
TI  - Endothelial function and cardiovascular disease: effects of quercetin and wine
      polyphenols.
AB  - Endothelial dysfunction is an early pathophysiological feature and independent
      predictor of poor prognosis in most forms of cardiovascular diseases.
      Epidemiological studies report an inverse association between dietary flavonoid
      consumption and mortality from cardiovascular diseases. In the present paper, we
      review the effects of flavonoids, especially quercetin and wine polyphenols, on
      endothelial function and dysfunction and its potential protective role in
      hypertension, ischemic heart disease and stroke. In vitro studies show that
      flavonoids may exert multiple actions on the NO-guanylyl cyclase pathway,
      endothelium-derived hyperpolarizing factor(s) and endothelin-1 and protect
      endothelial cells against apoptosis. In vivo, flavonoids prevent endothelial
      dysfunction and reduce blood pressure, oxidative stress and end-organ damage in
      hypertensive animals. Moreover, some clinical studies have shown that flavonoid
      rich foods can improve endothelial function in patients with hypertension and
      ischemic heart disease. Altogether, the available evidence indicates that
      quercetin and wine polyphenols might be of therapeutic benefit in cardiovascular
      diseases even though prospective controlled clinical studies are still lacking.

PMID- 17015251
TI  - Cardioprotective effect of resveratrol via HO-1 expression involves p38 map
      kinase and PI-3-kinase signaling, but does not involve NFkappaB.
AB  - Recent studies have demonstrated that resveratrol (trans-3,4',5-trihydroxy
      stilbene), a phytoalexin found in the skin and seeds of grapes, can
      pharmacologically precondition (PC) the heart through a nitric oxide (NO)
      dependent and adenosine receptors-mediated mechanism. Since NO can induce the
      expression of heme oxygenase-1 (HO-1), we examined if HO-1 induction has a direct
      role in resveratrol-preconditioning of the heart. Eight groups of rats were
      studied during 7 days: (i) control rats; (ii) rats receiving resveratrol (gavage,
      2.5 mg/kg); (iii) rats injected tin protoporphyrin (SnPP), a HO-1 inhibitor, i.p.
      on days 1, 3 and 6; (iv) rats injected 202190 (SB), a p38MAPK inhibitor, i.p. for
      7 days; (v) rats injected 294002 (LY), a Akt inhibitor, i.p. for 7days; (vi) rats
      receiving resveratrol and SnPP; (vii) rats receiving resveratrol and SB; and
      (viii) rats receiving resveratrol and LY. After the treatments, the rats were
      sacrificed, and the hearts isolated and subjected to 30 min global ischemia
      followed by 2 h of reperfusion. The results shown a significant cardioprotection
      with resveratrol as evidenced by superior post-ischemic ventricular recovery,
      reduced myocardial infarct size, and decreased number of apoptotic
      cardiomyocytes. SnPP treatment abolished the cardioprotective effect of
      resveratrol. Resveratrol induced the activation of nuclear factor kappa
      beta(NFkappaB), the phosphorylation of p38MAP kinase beta and Akt, as well as the
      inhibition of p38 MAP kinase alpha; all these effects but the activation of
      NFkappaB, were completely reversed by treatment with SnPP. These results indicate
      that resveratrol generates cardioprotection by preconditioning the heart by HO-1
      mediated mechanisms, which are regulated by p38MAP kinase and Akt survival
      signaling, but non-dependent on NFkappaB activation.

PMID- 17015252
TI  - Myeloperoxidase-mediated LDL oxidation and endothelial cell toxicity of oxidized
      LDL: attenuation by (-)-epicatechin.
AB  - Recent data suggest an inverse epidemiological association between intake of
      flavanol-rich cocoa products and cardiac mortality. Potential beneficial effect
      of cocoa may be attributed to flavanol-mediated improvement of endothelial
      function, as well as to enhancement of bioavailability and bioactivity of nitric
      oxide in vivo. ( - )-Epicatechin is one bioactive flavanol found in cocoa. This
      review deals with protective actions of ( - )-epicatechin on two key processes in
      atherogenesis, oxidation of LDL and damage to endothelial cell by oxidized LDL
      (oxLDL), with emphasis on data from this laboratory. ( - )-Epicatechin not only
      abrogates or attenuates LDL oxidation but also counteracts deleterious actions of
      oxLDL on vascular endothelial cells. These protective actions are only partially
      shared by other vasoprotective agents such as vitamins C and E or aspirin. Thus,
      ( - )-epicatechin appears to be a pleiotropic protectant for both LDL and
      endothelial cells.

PMID- 17015253
TI  - Modulation of transcription factor NF-kappaB in Hodgkin's lymphoma cell lines:
      effect of (-)-epicatechin.
AB  - Transcription factor NF-kappaB plays a central role in tumorogenesis and in
      different types of cancer, including Hodgkin's lymphoma. Previously, we described
      that ( - )-epicatechin (EC) inhibits PMA-induced NF-kappaB activation in Jurkat T
      cells. Therefore, we investigated the capacity of EC to inhibit NF-kappaB
      activation, the underlying mechanisms and the effects of EC on cell viability in
      Hodgkin's lymphoma cells. EC inhibited NF-kappaB-DNA binding activity in L-428
      and KM-H2 cells. This inhibition was not associated with EC antioxidant activity,
      with changes in p65 phosphorylation or NF-kappaB nuclear translocation. Results
      suggest that EC acted inhibiting the binding of NF-kappaB to DNA. The combined
      treatment with EC and an inhibitor of NF-kappaB nuclear translocation (SN-50)
      caused an additive inhibitory effect on NF-kappaB activation. The partial cell
      viability decrease, under conditions that EC and SN-50 completely prevented NF
      kappaB-DNA binding, indicates that the inhibition of other signaling pathways
      should be also targeted in the treatment of Hodgkin's lymphoma.

PMID- 17015254
TI  - Polyphenols from green tea and pomegranate for prevention of prostate cancer.
AB  - Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in North
      America with similar trends in many Western countries. Geographic,
      epidemiological and laboratory studies suggest a role for dietary constituents in
      the etiology as well as prevention of PCa. The rising incidence of PCa in several
      countries appears to be coincidental with adoption of western lifestyle. Increase
      in the incidence of PCa has also been found in Asian populations migrating to the
      west. These facts give numerous leads to explore testable PCa prevention
      strategies. There is growing evidence in support of use of dietary ingredients in
      prevention and treatment of PCa. While substantial data exists in favor of use of
      polyphenols from tea as PCa chemopreventive agent, interest in anti-cancer
      properties of polyphenols from pomegranate has recently emerged. This review
      summarizes current literature on the effects of polyphenols from green tea and
      pomegranate against PCa.

PMID- 17015255
TI  - A comparison of the neurotrophic activities of the flavonoid fisetin and some of
      its derivatives.
AB  - Neurotrophic factors promote the development, maintenance and regeneration of
      nerve cells. Classical neurotrophic factors are proteins and thus not well-suited
      for therapeutic purposes. Recently, we showed that specific flavonoids such as
      fisetin (3, 7, 3', 4' tetrahydroxyflavone) promote the differentiation of nerve
      cells in culture through the activation of extracellular signal-regulated kinase
      (ERK) suggesting that flavonoids could substitute for neurotrophic factors. It
      has also been shown that fisetin promotes nerve cell survival following exposure
      to toxic oxidative insults. To determine whether or not this is unique to
      fisetin, a series of related compounds were assayed for neurotrophic activities.
      Many of these related compounds also promote nerve cell differentiation and are
      neuroprotective against toxic oxidative insults. However, the mechanisms
      underlying these neurotrophic effects differ among the compounds.

PMID- 17015256
TI  - Part of the series: from dietary antioxidants to regulators in cellular signaling
      and gene regulation. Sulforaphane and selenium, partners in adaptive response and
      prevention of cancer.
AB  - The association of decreased cancer risk with intake of cruciferous vegetables
      and selenium is stronger than that reported for fruits and vegetables in general.
      An active constituent in cruciferae is sulforaphane. Chemopreventive effects of
      both, sulforaphane and selenium have been attributed to an antioxidant action
      which certainly is too simplicistic. Sulforaphane induces via activation of the
      Nrf2/Keap1 system phase 2 enzymes that protect against carcinogens and oxidants.
      Induced enzymes comprise the selenoproteins thioredoxin reductase-1 (TrxR1) and
      gastrointestinal glutathione peroxidase (GI-GPx, GPx2), which contain antioxidant
      response elements (ARE) in their promoter regions. Translational realisation of
      the enhanced transcripts depends on adequate selenium supply, which explains the
      synergism of Nrf2 activators and selenium. Regarding tumorigenesis the role of
      TrxR1 is ambiguous: it is essential for fast tumor cell growth but also
      diminishes vascularisation of tumors. The anticarcinogenic role of GI-GPx is
      evident from enhanced gastrointestinal tumor formation in gpx2/gpx1 double KO
      mice.

PMID- 17015257
TI  - Free radicals act as effectors in the growth inhibition and apoptosis of iron
      treated Burkitt's lymphoma cells.
AB  - The addition of ferric citrate to Burkitt's lymphoma (BL) cell lines inhibits
      growth, leads to the accumulation of cells in the phase G(2)/M of the cell cycle
      and to the modulation of translocated c-myc expression. The increase in the
      labile iron pool (LIP) of iron-treated BL cells leads to cytotoxicity. Indeed,
      intracellular free iron catalyzes the formation of highly reactive compounds such
      as hydroxyl radicals and nitric oxide (NO) that damages macromolecular components
      of cells, eventually resulting in apoptosis. In this report, we have investigated
      the possible involvement of free radicals in the response of Ramos cells to iron.
      When added to Ramos cells, iron increased the intracellular levels of
      peroxide/peroxynitrite and NO. Moreover, the addition of free radicals scavengers
      (TROLOX and Carboxy-PTIO) neutralized the effects of iron on Ramos cells while
      addition of an NO donor or hydrogen peroxide (H2O2) to cells generated effects
      which partially mimicked those induced by iron addition. Collectively, our
      results suggest the involvement of free radicals as effectors in the iron
      specific growth inhibition of BL cells observed in vitro.

PMID- 17015258
TI  - In the presence of ferritin, visible light induces lipid peroxidation of the
      porcine photoreceptor outer segment.
AB  - We studied the synergistic effect of visible light and ferritin on the lipid
      peroxidation on a fraction of porcine photoreceptor outer segment (POS). Reaction
      mixtures containing the POS fraction and horse spleen ferritin were irradiated
      under white fluorescent light mainly at 17,000 lx or incubated under dark
      conditions at 37 degrees C. The lipid peroxidation was evaluated by both the
      thiobarbituric acid method and the ferrous oxidation/xylenol orange method. The
      irradiation-induced lipid peroxidation was affected by some experimental factors
      such as the irradiation dose and acidity of the material. When the irradiation
      was stopped, the lipid peroxidation was also stopped; thereafter, the re
      irradiation induced lipid peroxidation. Moreover, this lipid peroxidation was
      inhibited by desferrioxamine, an iron chelator, or by dimethylthiourea, a
      hydroxyl radical scavenger, suggesting that the lipid peroxidation involves
      hydroxyl radicals generated via the Fenton reaction by iron ion released from
      ferritin. The lipid peroxidation did not take place under dark conditions or in
      the absence of ferritin. This study suggested the possibility that the visible
      light-induced lipid peroxidation of the POS fraction in the presence of ferritin
      may participate in the etiology of human retinal degenerative diseases as the
      human retina is exposed to light for life.

PMID- 17015259
TI  - Enzyme-linked immunosorbent assay for 4-hydroxynonenal-histidine conjugates.
AB  - Highly reactive aldehyde 4-hydroxynonenal (HNE) is the final product of lipid
      peroxidation, known as a second messenger of free radicals and a signaling
      molecule. It forms protein conjugates involved in pathology of various diseases.
      To determine cellular HNE-protein conjugates we developed indirect ELISA based on
      well-known, monoclonal antibody against HNE-histidine (HNE-His) adducts. The
      method was calibrated using HNE-albumin conjugates as standards (R(2) = 0.999)
      and validated on human osteosarcoma cell cultures (HOS). The ELISA showed good
      sensitivity (8.1 pmol HNE-His/mg of protein), precision ( +/- 8% intra-assay and
      +/- 12% inter-assay) and spiking recovery ( +/- 9%). The assay revealed 60-fold
      increase of cellular HNE-His adducts upon copper-induced lipid peroxidation of
      HOS. The ELISA matched HNE-immunocytochemistry of HNE-treated HOS cells and
      quantified the increase of cellular HNE-His conjugates in parallel to the
      decrease of free HNE in culture medium. The ELISA was developed as ELISA Stress
      for severe lipid peroxidation and ELISA Fine for studies on HNE physiology.

PMID- 17015260
TI  - Photodynamic action of C-phycocyanins obtained from marine and fresh water
      cyanobacterial cultures: a comparative study using EPR spin trapping technique.
AB  - C-phycocyanins, major biliproteins of blue green algae (cyanobacteria), widely
      used as colourants in food and cosmetics are known for their antioxidant as well
      as therapeutic potential. Recent claims indicating phycobiliproteins exert
      stronger photodynamic action on tumor cells than clinically approved
      hematoporphyrin derivatives motivate us to investigate the photodynamic action of
      two newly isolated C-phycocyanins from Phormidium [PHR] and Lyngbya [LY] spp,
      respectively in comparison with known C-phycocyanin from Spirulina sp. [SPI].
      Photolysis of air saturated solutions of PHR, LY and SPI in the presence of
      2,2,6,6-Tetramethyl piperidinol (TEMPL) generated three line EPR spectrum
      characteristic of 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxyl (TEMPOL). The
      increase in intensity of the EPR spectrum with time of irradiation and decrease
      in intensity, in the presence of 1O2 quencher DABCO confirm the formation of 1O2.
      Photoirradiation in the presence of spin trap 5,5-dimethyl-1-pyrroline-N-oxide
      (DMPO) generated EPR signal characteristic of O2(-) adduct. Efficiency of 1O2
      generation is of the order LY > PHR> SPI. The yield of reactive oxygen species
      (ROS) generation is found to be 1O2>O2(-) indicating type II mechanism to be the
      prominent pathway for photosensitation by phycocyanins.

PMID- 17015261
TI  - S-Allyl-L-cysteine attenuates cerebral ischemic injury by scavenging
      peroxynitrite and inhibiting the activity of extracellular signal-regulated
      kinase.
AB  - S-Allyl-L-cysteine (SAC) has been shown to reduce ischemic injury due to its
      antioxidant activity. However, the antioxidant property of SAC has been
      controversial. The present study investigated the neuroprotective mechanism of
      SAC in cerebral ischemic insults. SAC decreased the size of infarction after
      transient or global ischemic insults. While it did not alter the N-methyl-D
      aspartate excitotoxicity, SAC significantly scavenged the endogenously or
      exogenously produced ONOO- and reduced ONOO- cytotoxicity. In contrast, SAC has
      much lower scavenging activity against H2O2, O2*(-) or NO. Further, SAC inhibited
      the activity of extracellular signal-regulated kinase (ERK) increased in cultured
      neurons exposed to oxygen-glucose deprivation or in rat brain tissue after
      transient middle cerebral artery occlusion. The neuroprotective effect of SAC was
      mimicked by the ERK inhibitor U0125. The present results indicate that SAC exert
      its neuroprotective effect by scavenging ONOO- and inhibiting the ERK signaling
      pathway activated during initial hypoxic/ischemic insults.

PMID- 17015262
TI  - Effect of docosahexaenoic acid intake on lipid peroxidation in diabetic rat
      retina under oxidative stress.
AB  - Docosahexaenoic acid (DHA) plays an important role in visual function but has a
      highly oxidation-prone chemical structure. Therefore, we investigated how dietary
      DHA affects the generation of lipid peroxides in rat retina under oxidative
      stress in diabetes with/without vitamin E (VE) deficiency. Streptozotocin-induced
      (50 mg i.p./kg B.W.) diabetic Sprague-Dawley (SD) rats were assigned to four
      groups: (i) control/VE(+), (ii) DHA/VE(+), (iii) control/VE( - ) and (iv) DHA/VE(
      - ), and raised for 28 days. We then measured lipid peroxide levels in the
      retina, serum and liver. With a normal intake of VE, dietary DHA increased only
      the retinal level of thiobarbituric acid-reactive substances (TBARS) slightly. In
      contrast, in rats with VE deficiency, dietary DHA increased serum and liver lipid
      peroxide levels but not in the retina. These results suggest that dietary DHA
      does not necessarily promote lipid peroxidation in the retina even under high
      oxidative stress.

PMID- 17015263
TI  - Cobalt induces hypoxia-inducible factor-1alpha (HIF-1alpha) in HeLa cells by an
      iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism.
AB  - The iron-chelator desferrioxamine (DFO) and the transition metal cobalt induce
      hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. DFO stabilizes HIF
      1alpha from proteolysis by inhibiting the activity of iron-dependent prolyl
      hydroxylases, but the mechanism of action of cobalt is not fully elucidated. The
      purpose of this study was to examine the regulation of HIF-1alpha induction and
      HeLa cell proliferation by cobalt and the role of iron in these processes. Our
      results show that, unlike DFO, induction of transcriptionally active HIF-1alpha
      by CoCl2 cannot be abrogated by the addition of excess Fe3+, but involves the
      production of reactive oxygen species (ROS) and the operation of the
      phosphatidylinositol-3 kinase (PI-3K) and MAPK pathways. CoCl2, as well as DFO,
      decreased HeLa cell proliferation, but these effects were reversed by the
      addition of Fe3+. We conclude that the effect of cobalt on cell proliferation is
      iron-dependent, while its effects on HIF-1alpha induction are ROS- and signaling
      pathways-dependent, but iron-independent.

PMID- 17015264
TI  - Enhanced oxidation of NAD(P)H by oxidants in the presence of dehydrogenases but
      no evidence for a superoxide-propagated chain oxidation of the bound coenzymes.
AB  - Recently we demonstrated that lactate dehydrogenase (LDH)-bound NADH is oxidized
      by O2, H2O2, HNO2 and peroxynitrite predominantly via a chain radical mechanism
      which is propagated by superoxide. Here we studied both whether other
      dehydrogenases also increase their coenzymes' reactivity towards these oxidants
      and whether a chain radical mechanism is operating. Almost all dehydrogenases
      increased the oxidation of their physiological coenzymes by at least one of the
      oxidants. The oxidation of NADH or NADPH depended both on the binding
      dehydrogenase and the applied oxidant and in some cases the reactions were
      remarkably fast. The highest rate constant (k = 370 M-1 s-1) was found for the
      reaction of HNO2 with NADH bound to alcohol dehydrogenase. Regardless of the
      applied oxidant, superoxide dismutase failed to inhibit the oxidation of protein
      bound NADH and NADPH. We therefore conclude that several dehydrogenases increase
      the oxidation of NADH and/or NADPH by the employed set of oxidants in bimolecular
      reactions, but, unlike LDH, do not mediate a O2*(-) dependent chain radical
      mechanism.

PMID- 17015266
TI  - 4-Hydroxy-2-nonenal upregulates endogenous antioxidants and phase 2 enzymes in
      rat H9c2 myocardiac cells: protection against overt oxidative and electrophilic
      injury.
AB  - This study was undertaken to determine if 4-hydroxy-2-nonenal (HNE) could
      upregulate antioxidants and phase 2 enzymes in rat H9c2 myocardiac cells, and if
      the upregulated defenses led to cytoprotection against oxidative and
      electrophilic injury. Incubation of H9c2 cells with HNE at noncytotoxic
      concentrations resulted in significant induction of cellular catalase,
      glutathione (GSH), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase 1
      (NQO1), as determined by enzyme activity and/or protein expression. HNE treatment
      caused increased mRNA expression of catalase, gamma-glutamylcysteine ligase, GST
      A1, and NQO1. Pretreatment of H9c2 cells with HNE led to significant protection
      against cytotoxicity induced by reactive oxygen and nitrogen species. HNE
      pretreated cells also exhibited increased resistance to injury elicited by
      subsequent cytotoxic concentrations of HNE. Taken together, this study
      demonstrates that several antioxidants and phase 2 enzymes in H9c2 cells are
      upregulated by HNE and that the increased defenses afford protection against
      overt oxidative and electrophilic cardiac cell injury.

PMID- 17015265
TI  - The ADP-stimulated NADPH oxidase activates the ASK-1/MKK4/JNK pathway in alveolar
      macrophages.
AB  - The role of H2O2 as a second messenger in signal transduction pathways is well
      established. We show here that the NADPH oxidase-dependent production of O2*(-)
      and H2O2 or respiratory burst in alveolar macrophages (AM) (NR8383 cells) is
      required for ADP-stimulated c-Jun phosphorylation and the activation of JNK1/2,
      MKK4 (but not MKK7) and apoptosis signal-regulating kinase-1 (ASK1). ASK1 binds
      only to the reduced form of thioredoxin (Trx). ADP induced the dissociation of
      ASK1/Trx complex and thus resulted in ASK1 activation, as assessed by
      phosphorylation at Thr845, which was enhanced after treatment with
      aurothioglucose (ATG), an inhibitor of Trx reductase. While dissociation of the
      complex implies Trx oxidation, protein electrophoretic mobility shift assay
      detected oxidation of Trx only after bolus H2O2 but not after ADP stimulation.
      These results demonstrate that the ADP-stimulated respiratory burst activated the
      ASK1-MKK4-JNK1/c-Jun signaling pathway in AM and suggest that transient and
      localized oxidation of Trx by the NADPH oxidase-mediated generation of H2O2 may
      play a critical role in ASK1 activation and the inflammatory response.

PMID- 17015267
TI  - Interactions between the OGG1 Ser326Cys polymorphism and intake of fruit and
      vegetables in relation to lung cancer.
AB  - The enzyme 8-oxoguanine glycosylase 1 (OGG1) repairs oxidatively damaged DNA and
      a polymorphism in the OGG1 gene (Ser326Cys) has been associated with lung cancer.
      We examined associations between the polymorphism and intake of fruits and
      vegetables and smoking in the development of lung cancer, by genotyping blood
      samples from 431 lung cancer cases and 796 comparison persons, which were
      identified within a prospective cohort on 57,000 cohort members. We found no
      overall association between the OGG1 polymorphism and lung cancer. There was a
      statistically significant interaction between the polymorphism and dietary intake
      of vegetables, with a 54% decrease in lung cancer risk per 50% increase in
      vegetable intake among homozygous Cys326Cys carriers and no decrease in risk
      among carriers of Ser326Ser or Ser326Cys. The same tendency was seen in relation
      to intake of fruit. There were no statistically significant interactions between
      the OGG1 polymorphism and smoking.

PMID- 17015268
TI  - Changes in plasma alpha and gamma tocopherol levels before and after long-term
      local hyperthermia in cancer patients.
AB  - Local hyperthermia is one of the heat therapies for cancer patients. The effect
      of this therapy is recognized to affect the immune function. On the other hand,
      researchers have recently suggested that vitamin E has not only antioxidant but
      also other functions including the immune function. However, the association
      between local hyperthermia therapy and vitamin E level is not yet well
      understood. Comparing plasma alpha and gamma tocopherol levels before and after
      the therapy, the basal levels of both tocopherols in the cancer patients did not
      significantly differ from those in healthy subjects. However, the interindividual
      difference in the basal levels was very wide in the cancer patients. After long
      term local hyperthermia (more than 70 days), the levels of both tocopherols were
      significantly higher than the basal levels. This result suggests that long-term
      local hyperthermia therapy influences plasma tocopherol level in cancer patients;
      thus, an increase in vitamin E level may play an important role in the therapy of
      cancer patients.

PMID- 17015269
TI  - Free radicals in exhaled breath condensate in cystic fibrosis and healthy
      subjects.
AB  - Many markers of airway inflammation and oxidative stress can be measured non
      invasively in exhaled breath condensate (EBC). However, no attempt has been made
      to directly detect free radicals using electron paramagnetic resonance (EPR)
      spectroscopy. Condensate was collected in 14 children with cystic fibrosis (CF)
      and seven healthy subjects. Free radicals were trapped by 5,5-dimethyl-1
      pyrroline-N-oxide. EPR spectra were recorded using a Bruker EMX spectrometer.
      Secondly, to study the source of oxygen centered radical formation, catalase or
      hydrogen peroxide was added to the condensate. Radicals were detected in 18 out
      of 21 condensate samples. Analysis of spectra indicated that both oxygen and
      carbon centered radicals were trapped. Within-subject reproducibility was good in
      all but one subject. Quantitatively, there was a trend towards higher maximal
      peak heights of both oxygen and carbon centered radicals in the children with CF.
      Catalase completely suppressed the signals in condensate. Addition of hydrogen
      peroxide resulted in increased radical signal intensity. Detection of free
      radicals in EBC of children with CF and healthy subjects is feasible using EPR
      spectroscopy.

PMID- 17015270
TI  - Melatonin nitrosation promoted by NO*2; comparison with the peroxynitrite
      reaction.
AB  - N-nitroso species have recently been detected in animal tissues. Protein N
      nitrosotryptophan is the best candidate for this N-nitroso pool. N-nitrosation of
      N-blocked trytophan derivatives like melatonin (MelH) by N2O3 or peroxynitrite
      (ONOOH/ONOO- ) has been observed under conditions of pH and reagent
      concentrations similar to in vivo conditions. We studied the reaction of NO*2
      with MelH. When NO*2 was synthesized by gamma-irradiation of aqueous neutral
      solutions of nitrate under anaerobic conditions, detected oxidation and nitration
      of MelH were negligible. In the presence of additional nitrite, when NO* was also
      generated, formation of 1-nitrosomelatonin increased with nitrite concentration.
      Nitrosation is not due to N2O3 but could proceed via successive additions of NO*2
      and NO*. For comparison, peroxynitrite was infused into a solution of MelH under
      air leading to the same products as those detected in irradiated solutions but in
      different proportions. In the presence of additional nitrite, the formation of
      nitroderivatives increased significantly while N-formylkynuramine and 1
      nitrosomelatonin were maintained at similar levels. Mechanistic implications are
      discussed.

PMID- 17015271
TI  - Differential regulation of hepatic cytochrome P450 monooxygenases in
      streptozotocin-induced diabetic rats.
AB  - The present investigation was carried out to study the expression of major
      cytochrome P450 (CYP) isozymes in streptozotocin-induced diabetes with
      concomitant insulin therapy. Male Sprague-Dawley rats were randomly assigned to
      untreated control, streptozotocin-induced diabetic, insulin-treated groups and
      monitored for 4 weeks. Uncontrolled hyperglycemia in the early phase of diabetes
      resulted in differential regulation of cytochrome P450 isozymes. CYP1B1, CYP1A2,
      heme oxygenase (HO)-2 proteins and CYP1A2-dependent 7-ethoxyresorufin O
      deethylase (EROD) activity were upregulated in the hepatic microsomes of diabetic
      rats. Insulin therapy ameliorated EROD activity and the expression of CYP1A2,
      CYP1B1 and HO-2 proteins. In addition, CYP2B1 and 2E1 proteins were markedly
      induced in the diabetic group. Insulin therapy resulted in complete amelioration
      of CYP2E1 whereas CYP2B1 protein was partially ameliorated. By contrast, CYP2C11
      protein was decreased over 99% in the diabetic group and was partially
      ameliorated by insulin therapy. These results demonstrate widespread alterations
      in the expression of CYP isozymes in diabetic rats that are ameliorated by
      insulin therapy.

PMID- 17015272
TI  - Methionine challenge paradoxically induces a greater activation of the
      antioxidant defence in subjects with hyper- vs. normohomocysteinemia.
AB  - To determine whether hyperhomocysteinemia induced post-methionine loading (PML)
      is associated with different response in the aminothiol redox state and oxidative
      stress vs. normohomocysteinemia, we assessed PML plasma thiols, vitamins, free
      malondialdehyde (MDA), and blood reduced glutathione (GSH) in 120 consecutive
      subjects (50 [35-56] years, 83 males), divided into two groups according to PML
      plasma total Hcy < 35 microM (Group 1, n = 65) or > or = 35 microM (Group 2, n =
      55). In the group as a whole, plasma reduced cysteine and cysteinylglycine, blood
      reduced GSH (all p for time = 0.0001) and plasma total GSH (p for time = 0.001)
      increased from baseline to PML. MDA values were unchanged. Group 1 and 2 differed
      in blood reduced GSH (p for group = 0.004, higher in Group 2), and MDA levels (p
      for group = 0.024, lower in Group 2). The oxidative stress induced by methionine
      challenge seems to be opposed by scavenger molecules activation, namely GSH, and
      lipid peroxidation does not increase. This mechanism paradoxically appears to be
      more efficient in hyperhomocysteinemic subjects.

PMID- 17015273
TI  - Selenoprotein P protects endothelial cells from oxidative damage by stimulation
      of glutathione peroxidase expression and activity.
AB  - A major fraction of the essential trace element selenium circulating in human
      blood plasma is present as selenoprotein P (SeP). As SeP associates with
      endothelial membranes, the participation of SeP in selenium-mediated protection
      against oxidative damage was investigated, using the human endothelial cell line
      Ea.hy926 as a model system. Hepatocyte-derived SeP prevented tert
      butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a
      similar manner as did sodium selenite, counteracting a t-BHP-induced loss of
      cellular membrane integrity. Protection was detected after at least 10 h of SeP
      supplementation and it peaked at 24 h. SeP time-dependently stimulated the
      expression of cytosolic glutathione peroxidase (cGPx) and increased the enzymatic
      activities of glutathione peroxidase (GPx) and thioredoxin reductase (TR). The
      cGPx inhibitor mercaptosuccinate as well as the gamma-glutamylcysteine synthetase
      inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while
      the TR inhibitors cisplatin and auranofin had no effect. The presented data
      suggest that selenium supplementation by SeP prevents oxidative damage of human
      endothelial cells by restoring expression and enzymatic activity of GPx.

PMID- 17015274
TI  - Estimation of hydroxyl radical generation by salicylate hydroxylation method in
      multiple organs of mice exposed to whole-body X-ray irradiation.
AB  - Appropriate experimental conditions for the estimation of hydroxyl radical
      generation by salicylate hydroxylation were determined for multiple organs of X
      irradiated mice in vivo. The in vitro experiments showed that there were
      significant correlations between the salicylic acid (SA) concentration, the
      amount of 2,3-dihydroxy benzoic acid (2,3-DHBA) and the X-ray exposure dose, and
      we obtained two linear-regression equations to calculate the amounts of hydroxyl
      radicals generated by the X-irradiation. The optimum dosage of SA and the
      appropriate sampling time for in vivo experiments was determined, and significant
      increases in the ratio of 2,3-DHBA to SA were detected in several organs of mice
      after X-irradiation. The hydroxyl radical equivalents of the 2,3-DHBA increases
      were also calculated. Our results clearly demonstrated the usefulness of the
      salicylate hydroxylation method in estimating hydroxyl radical generation in
      multiple organs in vivo.

PMID- 17015275
TI  - Human blood plasma advanced oxidation protein products (AOPP) correlates with
      fibrinogen levels.
AB  - In 1996 a novel oxidative stress biomarker, referred to as advanced oxidation
      protein products (AOPP) was detected in the plasma of chronic uremic patients.
      The aim of the present studies was to find out that which plasma fraction(s) is
      responsible for AOPP reactivity. Thermal treatment of pooled samples of human
      citrate-plasma or EDTA-plasma at 50 degrees C resulted in a rapid and parallel
      loss of fibrinogen concentration and AOPP reactivity. On the basis of time course
      and t1/2 values following thermal treatment, AOPP was indistinguishable from
      fibrinogen. There was a statistically significant (p < 0.0001) correlation
      between levels of blood plasma fibrinogen and AOPP in patients (n = 61) with
      various peripheral vascular or cardiovascular diseases. There was also a
      significant (p < 0.0001) relationship between plasma levels of fibrinogen and
      molar AOPP/fibrinogen ratio indicating that higher fibrinogen concentrations were
      associated with more oxidatively transformed groups on the molecule. Results of
      the present studies suggest that post-translationally modified fibrinogen is a
      key molecule responsible for human plasma AOPP reactivity. It remains to be
      elucidated what is the pathophysiological significance of the post
      translationally modified fibrinogen in the inflammation-associated events of
      atherosclerosis, in platelet aggregation, and as a cardiovascular risk biomarker.

PMID- 17015276
TI  - Generation of a novel fluorescent product, monochlorofluorescein from
      dichlorofluorescin by photo-irradiationdagger.
AB  - Dichlorofluorescin (DCFH), a widely used fluorescent probe for reactive oxygen
      species (ROS) was decomposed completely and generated two distinct fluorescent
      products by photo-irradiation at 254 nm for 30 min. In the previous study, we had
      shown that one was dichlorofluorescein (DCF), a well known oxidized product of
      DCFH. In this study we investigated the other product and identified it as
      monochlorofluorescein (MCF) by 1H-NMR and fast atom bombardment/mass spectrum
      (FAB/MS) analyses. MCF was generated by photo-irradiation, but not by ROS. On the
      other hand, DCF was produced by both photo-irradiation and ROS. MCF showed
      similar fluorescent emission spectrum to DCF, however, its fluorescence intensity
      was more than that of DCF. The kinetic study suggested that MCF was not generated
      from DCF but from monochlorofluorescin, which might be generated from DCFH by
      photo-irradiation.

PMID- 17015277
TI  - Mechanism of oxidative DNA damage induced by capsaicin, a principal ingredient of
      hot chili pepper.
AB  - Although capsaicin exhibits antitumor activity, carcinogenic potential has also
      been reported. To clarify the mechanism for expression of potential
      carcinogenicity of capsaicin, we examined DNA damage induced by capsaicin in the
      presence of metal ion and various kinds of cytochrome P450 (CYP) using 32P-5'-end
      labeled DNA fragments. Capsaicin induced Cu(II)-mediated DNA damage efficiently
      in the presence of CYP1A2 and partially in the presence of 2D6. CYP1A2-treated
      capsaicin caused double-base lesions at 5'-TG-3', 5'-GC-3' and CG of the 5'-ACG
      3' sequence complementary to codon 273, a hotspot of p53 gene. DNA damage was
      inhibited by catalase and bathocuproine, a Cu(I) chelator, suggesting that
      reactive species derived from the reaction of H2O2 with Cu(I) participate in DNA
      damage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine was significantly
      increased by CYP1A2-treated capsaicin in the presence of Cu(II). Therefore, we
      conclude that Cu(II)-mediated oxidative DNA damage by CYP-treated capsaicin seems
      to be relevant for the expression of its carcinogenicity.

PMID- 17015278
TI  - The reductive activation of the antitumor drug RH1 to its semiquinone free
      radical by NADPH cytochrome P450 reductase and by HCT116 human colon cancer
      cells.
AB  - RH1 (2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone), which is
      currently in clinical trials, is a diaziridinyl benzoquinone bioreductive
      anticancer drug that was designed to be activated by the obligate two-electron
      reductive enzyme NAD(P)H quinone oxidoreductase 1 (NQO1). In this electron
      paramagnetic resonance (EPR) study we showed that RH1 was reductively activated
      by the one-electron reductive enzyme NADPH cytochrome P450 reductase and by a
      suspension of HCT116 human colon cancer cells to yield a semiquinone free
      radical. As shown by EPR spin trapping experiments RH1 was reductively activated
      by cytochrome P450 reductase and underwent redox cycling to produce damaging
      hydroxyl radicals in reactions that were both H2O2- and iron-dependent. Thus,
      reductive activation by cytochrome P450 reductase or other reductases to produce
      a semiquinone that can redox cycle to produce damaging hydroxyl radicals and/or
      DNA-reactive alkylating species may contribute to the potent cell growth
      inhibitory effects of RH1. These results also suggest that selection of patients
      for treatment with RH1 based on their expression levels of NQO1 may be
      problematic.

PMID- 17015279
TI  - A novel and simple ORAC methodology based on the interaction of Pyrogallol Red
      with peroxyl radicals.
AB  - Oxygen radicals absorbance capacities (ORAC) indexes are frequently employed to
      characterize the radical trapping capacity of pure compounds and their complex
      mixtures. A drawback of ORAC values obtained using phycoerythrin, fluorescein
      (FL) or c-phycocyanin as targets, makes it possible to conclude that for very
      reactive compounds they are much more related to stoichiometric factors than to
      the reactivity of the tested compound. In the present paper, we propose a simple
      methodology, based on the bleaching of Pyrogallol Red (PGR) absorbance that
      provides ORAC indexes that are almost exclusively determined by the reactivity of
      the tested compounds. This difference is due to the high reactivity of PGR and
      the high concentrations of this compound employed in the experiments.

PMID- 17015280
TI  - Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3'-di(beta-d
      glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4
      induced liver damage.
AB  - We investigated hepatoprotective activity and antioxidant effect of the 2,5
      dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene that purified from
      Morus bombycis Koidzumi roots against CCl4-induced liver damage in rats. The 2,5
      dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene displayed dose
      dependent superoxide radical scavenging activity (IC50 = 430.2 microg/ml), as
      assayed by the electron spin resonance (ESR) spin-trapping technique. The
      increase in aspartate aminotransferase (AST) activities in serum associated with
      carbon tetrachloride (CCl4)-induced liver injury was inhibited by 2,5-dihydroxy
      4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene and at a dose of 400 - 600 mg/kg
      samples had hepatoprotective activity comparable to the standard agent,
      silymarin. The biochemical assays were confirmed by histological observations
      showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene
      decreased cell ballooning in response to CCl4 treatment. These results
      demonstrate that the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans
      stilbene is a potent antioxidant with a liver protective action against CCl4
      induced hepatotoxicity.

PMID- 17015281
TI  - Superoxide radical- and peroxynitrite-scavenging activity of anthocyanins;
      structure-activity relationship and their synergism.
AB  - Antioxidant activities of 15 purified bilberry anthocyanins together with
      pelargonidin 3-O-beta-D-glucopyranoside and 4'-O-methyl delphinidin 3-O-beta-D
      glucopyranoside (MDp 3-glc), the major metabolite of delphinidin 3-O-beta-D
      glucopyranoside (Dp 3-glc), were evaluated in order to study the structure
      antioxidant activity relationship and any synergism among them in the mixture.
      Both aglycone structure and the attached sugar moiety affected the O*2- and ONOO-
      -scavenging activities, although the effect of the attached sugar moiety was
      smaller than that of the aglycone structure. The potency of activity toward the
      superoxide radical was in the following order: delphinidin > petunidin > malvidin
      =approximately cyanidin>(+)-catechin > peonidin > pelargonidin. The activity
      toward ONOO- was: delphinidin > cyanidin =approximately petunidin > malvidin
      =approximately (+)-catechin > peonidin > pelargonidin. It was confirmed that
      methylation of 4'-OH markedly reduced the antioxidant activity of anthocyanin.
      Further, it was revealed that synergism occurred in both - and ONOO- -scavenging
      activities among the anthocyanins in the mixture.

PMID- 17015282
TI  - Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in
      children suffering from attention deficit/hyperactivity disorder.
AB  - The purpose of this randomized, double-blind and placebo controlled study was to
      test the effect of polyphenolic extract of pine bark Pycnogenol (Pyc) on the
      level of oxidized purines represented by 8-oxo-7,8-dihydroguanine (8-oxoG) and on
      the total antioxidant status (TAS) in children with attention
      deficit/hyperactivity disorder (ADHD).We have found significantly increased
      damage to DNA in ADHD children when compared to controls. 8-oxoG was
      significantly lower after 1 month of Pyc administration in comparison to the
      beginning state and to placebo group. TAS in ADHD children was lower in
      comparison to controls. After Pyc administration, TAS was elevated but
      statistically significant increase was recorded after 1 month of termination of
      Pyc application. Improvement of DNA damage and TAS after Pyc administration is
      associated with the improvement of attention in ADHD children. In conclusion,
      Pycnogenol(R) administration reduces oxidative damage to DNA, normalizes TAS and
      improves attention of ADHD children. Explanation of mutual relation between
      oxidative damage to DNA, TAS and symptoms of ADHD and mechanism of Pyc's action
      needs further investigations.

PMID- 17015284
TI  - 2005 Annual Report of the American Association of Poison Control Centers'
      national poisoning and exposure database.
AB  - BACKGROUND: The American Association of Poison Control Centers (AAPCC; <a
      href="http://www.aapcc.org" target="BLANK">http://www.aapcc.org</a>) maintains
      the national database of information logged by the country's 61 Poison Control
      Centers (PCCs). Case records in this database are from self-reported calls: they
      reflect only information provided when the public or healthcare professionals
      report an actual or potential exposure to a substance (e.g., an ingestion,
      inhalation, or topical exposure.), or request information/educational materials.
      Exposures do not necessarily represent a poisoning or overdose. The AAPCC is not
      able to completely verify the accuracy of every report made to member centers.
      Additional exposures may go unreported to PCCs, and data referenced from the
      AAPCC should not be construed to represent the complete incidence of national
      exposures to any substance(s). U.S. Poison Centers make possible the compilation
      and reporting of this report through their staffs' meticulous documentation of
      each case using standardized definitions and compatible computer systems. The 61
      participating poison centers in 2005 are: Regional Poison Control Center,
      Birmingham, AL; Alabama Poison Center, Tuscaloosa, AL; Arizona Poison and Drug
      Information Center, Tucson, AZ; Banner Poison Control Center, Phoenix, AZ;
      Arkansas Poison and Drug Information Center, Little Rock, AK; California Poison
      Control System-Fresno/Madera Division, CA; California Poison Control System
      Sacramento Division, CA; California Poison Control System-San Diego Division, CA;
      California Poison Control System-San Francisco Division, CA; Rocky Mountain
      Poison and Drug Center, Denver, CO; Connecticut Poison Control Center,
      Farmington, CT; National Capital Poison Center, Washington, DC; Florida Poison
      Information Center, Tampa, FL; Florida Poison Information Center, Jacksonville,
      FL; Florida Poison Information Center, Miami, FL; Georgia Poison Center, Atlanta,
      GA; Illinois Poison Center, Chicago, IL; Indiana Poison Center, Indianapolis, IN;
      Iowa Statewide Poison Control Center, Sioux City, IA; Mid-America Poison Control
      Center, Kansas City, KA; Kentucky Regional Poison Center, Louisville, KY;
      Louisiana Drug and Poison Information Center, Monroe, LA; Northern New England
      Poison Center, Portland, ME; Maryland Poison Center, Baltimore, MD; Regional
      Center for Poison Control and Prevention Serving Massachusetts and Rhode Island,
      Boston, MA; Children's Hospital of Michigan Regional Poison Control Center,
      Detroit, MI; DeVos Children's Hospital Regional Poison Center, Grand Rapids, MI;
      Hennepin Regional Poison Center, Minneapolis, MN; Mississippi Regional Poison
      Control Center, Jackson, MS; Missouri Regional Poison Center, St Louis, MO;
      Nebraska Regional Poison Center, Omaha, NE; New Jersey Poison Information and
      Education System, Newark, NJ; New Mexico Poison and Drug Information Center,
      Albuquerque, NM; New York City Poison Control Center, New York, NY; Long Island
      Regional Poison and Drug Information Center, Mineola, NY; Ruth A. Lawrence Poison
      and Drug Information Center, Rochester, NY; Upstate (formerly Central) New York
      Poison Center, Syracuse, NY; Western New York Poison Center, Buffalo, NY;
      Carolinas Poison Center, Charlotte, NC; Cincinnati Drug and Poison Information
      Center, Cincinnati, OH; Central Ohio Poison Center, Columbus, OH; Greater
      Cleveland Poison Control Center, Cleveland, OH; Oklahoma Poison Control Center,
      Oklahoma City, OK; Oregon Poison Center, Portland, OR; Pittsburgh Poison Center,
      Pittsburgh, PA; The Poison Control Center, Philadelphia, PA; Puerto Rico Poison
      Center, San Juan, PR; Palmetto Poison Center, Columbia, SC; Tennessee Poison
      Center, Nashville, TN; Central Texas Poison Center, Temple, TX; North Texas
      Poison Center, Dallas, TX; Southeast Texas Poison Center, Galveston, TX; Texas
      Panhandle Poison Center, Amarillo, TX; West Texas Regional Poison Center, El
      Paso, TX; South Texas Poison Center, San Antonio, TX; Utah Poison Control Center,
      Salt Lake City, UT; Virginia Poison Center, Richmond, VA; Blue Ridge Poison
      Center, Charlottesville, VA; Washington Poison Center, Seattle, WA; West Virginia
      Poison Center, Charleston, WV; Wisconsin Poison Center, Milwaukee, WI.

PMID- 17015285
TI  - The reinfection threshold regulates pathogen diversity: the case of influenza.
AB  - The awareness that pathogens can adapt and evolve over relatively short time
      scales is changing our view of infectious disease epidemiology and control.
      Research on the transmission dynamics of antigenically diverse pathogens is
      progressing and there is increasing recognition for the need of new concepts and
      theories. Mathematical models have been developed considering the modelling unit
      in two extreme scales: either diversity is not explicitly represented or
      diversity is represented at the finest scale of single variants. Here, we use an
      intermediate approach and construct a model at the scale of clusters of variants.
      The model captures essential properties of more detailed systems and is much more
      amenable to mathematical treatment. Specificities of pathogen clusters and the
      overall potential for transmission determine the reinfection rates. These are, in
      turn, important regulators of cluster dynamics. Ultimately, we detect a
      reinfection threshold (RT) that separates different behaviours along the
      transmissibility axis: below RT, levels of infection are low and cluster
      substitutions are probable; while above RT, levels of infection are high and
      multiple cluster coexistence is the most probable outcome.

PMID- 17015286
TI  - The feeding dynamics of broiler chickens.
AB  - Contrary to a commonly held belief that broiler chickens need more space, there
      is increasing evidence that these birds are attracted to other birds. Indeed,
      commercially farmed birds exhibit a range of socially facilitated behaviours,
      such as increased feeding and preening in response to the presence of other
      birds. Social facilitation can generate feedback loops, whereby the adoption of a
      particular behaviour can spread rapidly and suddenly through the population.
      Here, by measuring the rate at which broiler chickens join and leave a feeding
      trough as a function of the number of birds already there, we quantify social
      facilitation. We use these measurements to parameterize a simulation model of
      chicken feeding behaviour. This model predicts, and further observations of
      broiler chickens confirm, that social facilitation leads to excitatory and
      synchronized patterns of group feeding. Such models could prove a powerful tool
      in understanding how feeding patterns depend on broiler house design.

PMID- 17015287
TI  - Nonlinear mechanics of soft fibrous networks.
AB  - Mechanical networks of fibres arise on a range of scales in nature and
      technology, from the cytoskeleton of a cell to blood clots, from textiles and
      felts to skin and collageneous tissues. Their collective response is dependent on
      the individual response of the constituent filaments as well as density, topology
      and order in the network. Here, we use the example of a low-density synthetic
      felt of athermal filaments to study the generic features of the mechanical
      response of such networks including strain stiffening and large effective Poisson
      ratios. A simple microscopic model allows us to explain these features of our
      observations, and provides us with a baseline framework to understand active
      biomechanical networks.

PMID- 17015288
TI  - The interplay between a self-organized process and an environmental template:
      corpse clustering under the influence of air currents in ants.
AB  - Many spatial patterns observed in nature emerge from local processes and their
      interactions with the local environment. The clustering of objects by social
      insects represents such a pattern formation process that can be observed at both
      the individual and the collective level. In this paper, we study the interaction
      between air currents and clustering behaviour in order to address the
      coordinating mechanisms at the individual level that underlie the spatial pattern
      formation process in a heterogeneous environment. We choose the corpse clustering
      behaviour of the ant Messor sanctus as an experimental paradigm. In a
      specifically designed experimental set-up with a well-controlled laminar air flow
      (approx. 1 cm s-1), we first quantify the modulation of the individual corpse
      aggregation behaviour as a function of corpse density, air flow intensity and the
      ant's position with respect to corpse piles and air flow direction. We then
      explore by numerical simulation how the forming corpse piles modify the laminar
      air flow around them and link this result with the individual behaviour
      modulation. Finally, we demonstrate on the collective level that this laminar air
      flow leads to an elongation and a slow displacement of the formed corpse piles in
      the direction of the air current. Both the individual behaviour modulated by air
      flow and the air flow modulated by the forming corpse piles can explain the pile
      patterns observed on the collective level as a stigmergic process. We discuss the
      generality of this coordinating mechanism to explain the clustering phenomena in
      heterogeneous environments reported in the literature.

PMID- 17015289
TI  - Embryonic nodal flow and the dynamics of nodal vesicular parcels.
AB  - We address with fluid-dynamical simulations using direct numerical techniques
      three important and fundamental questions with respect to fluid flow within the
      mouse node and left-right development. First, we consider the differences between
      what is experimentally observed when assessing cilium-induced fluid flow in the
      mouse node in vitro and what is to be expected in vivo. The distinction is that
      in vivo, the leftward fluid flow across the mouse node takes place within a
      closed system and is consequently confined, while this is no longer the case on
      removing the covering membrane and immersing the embryo in a fluid-filled volume
      to perform in vitro experiments. Although there is a central leftward flow in
      both instances, we elucidate some important distinctions about the closed in vivo
      situation. Second, we model the movement of the newly discovered nodal vesicular
      parcels (NVPs) across the node and demonstrate that the flow should indeed cause
      them to accumulate on the left side of the node, as required for symmetry
      breaking. Third, we discuss the rupture of NVPs. Based on the biophysical
      properties of these vesicles, we argue that the morphogens they contain are
      likely not delivered to the surrounding cells by their mechanical rupture either
      by the cilia or the flow, and rupture must instead be induced by an as yet
      undiscovered biochemical mechanism.

PMID- 17015290
TI  - Mineral minimization in nature's alternative teeth.
AB  - Contrary to conventional wisdom, mineralization is not the only strategy evolved
      for the formation of hard, stiff materials. Indeed, the sclerotized mouthparts of
      marine invertebrates exhibit Young's modulus and hardness approaching 10 and 1
      GPa, respectively, with little to no help from mineralization. Based on
      biochemical analyses, three of these mouthparts, the jaws of glycerid and nereid
      polychaetes and a squid beak, reveal a largely organic composition dominated by
      glycine- and histidine-rich proteins. Despite the well-known metal ion binding by
      the imidazole side-chain of histidine and the suggestion that this interaction
      provides mechanical support in nereid jaws, there is at present no universal
      molecular explanation for the relationship of histidine to mechanical properties
      in these sclerotized structures.

PMID- 17015291
TI  - Evaluating candidate agents of selective pressure for cystic fibrosis.
AB  - Cystic fibrosis is the most common lethal single-gene mutation in people of
      European descent, with a carrier frequency upwards of 2%. Based upon molecular
      research, resistances in the heterozygote to cholera and typhoid fever have been
      proposed to explain the persistence of the mutation. Using a population genetic
      model parameterized with historical demographic and epidemiological data, we show
      that neither cholera nor typhoid fever provided enough historical selective
      pressure to produce the modern incidence of cystic fibrosis. However, we
      demonstrate that the European tuberculosis pandemic beginning in the seventeenth
      century would have provided sufficient historical, geographically appropriate
      selective pressure under conservative assumptions. Tuberculosis has been
      underappreciated as a possible selective agent in producing cystic fibrosis but
      has clinical, molecular and now historical, geographical and epidemiological
      support. Implications for the future trajectory of cystic fibrosis are discussed.
      Our result supports the importance of novel investigations into the role of
      arylsulphatase B deficiency in cystic fibrosis and tuberculosis.

PMID- 17015292
TI  - Material properties of brachiopod shell ultrastructure by nanoindentation.
AB  - Mineral-producing organisms exert exquisite control on all aspects of biomineral
      production. Among shell-bearing organisms, a wide range of mineral fabrics are
      developed reflecting diverse modes of life that require different material
      properties. Our knowledge of how biomineral structures relate to material
      properties is still limited because it requires the determination of these
      properties on a detailed scale. Nanoindentation, mostly applied in engineering
      and materials science, is used here to assess, at the microstructural level,
      material properties of two calcite brachiopods living in the same environment but
      with different modes of life and shell ultrastructure. Values of hardness (H) and
      the Young modulus of elasticity (E) are determined by nanoindentation. In
      brachiopod shells, calcite semi-nacre provides a harder and stiffer structure (H
      approximately 3-6 GPa; E=60-110/120 GPa) than calcite fibres (H=0-3 GPa; E=20
      60/80 GPa). Thus, brachiopods with calcite semi-nacre can cement to a substrate
      and remain immobile during their adult life cycle. This correlation between mode
      of life and material properties, as a consequence of ultrastructure, begins to
      explain why organisms produce a wide range of structures using the same chemical
      components, such as calcium carbonate.

PMID- 17015293
TI  - Modelling the checkpoint response to telomere uncapping in budding yeast.
AB  - One of the DNA damage-response mechanisms in budding yeast is temporary cell
      cycle arrest while DNA repair takes place. The DNA damage response requires the
      coordinated interaction between DNA repair and checkpoint pathways. Telomeres of
      budding yeast are capped by the Cdc13 complex. In the temperature-sensitive cdc13
      1 strain, telomeres are unprotected over a specific temperature range leading to
      activation of the DNA damage response and subsequently cell-cycle arrest.
      Inactivation of cdc13-1 results in the generation of long regions of single
      stranded DNA (ssDNA) and is affected by the activity of various checkpoint
      proteins and nucleases. This paper describes a mathematical model of how uncapped
      telomeres in budding yeast initiate the checkpoint pathway leading to cell-cycle
      arrest. The model was encoded in the Systems Biology Markup Language (SBML) and
      simulated using the stochastic simulation system Biology of Ageing e-Science
      Integration and Simulation (BASIS). Each simulation follows the time course of
      one mother cell keeping track of the number of cell divisions, the level of
      activity of each of the checkpoint proteins, the activity of nucleases and the
      amount of ssDNA generated. The model can be used to carry out a variety of in
      silico experiments in which different genes are knocked out and the results of
      simulation are compared to experimental data. Possible extensions to the model
      are also discussed.

PMID- 17015294
TI  - Neutral fitness landscapes in signalling networks.
AB  - Biological and technological systems process information by means of cascades of
      signals. Be they interacting genes, spiking neurons or electronic transistors,
      information travels across these systems, producing, for each set of external
      conditions, an appropriate response. In technology, circuits performing specific
      complex tasks are designed by humans. In biology, however, design has to be ruled
      out, confronting us with the question of how these systems could have arisen by
      accumulation of small changes. The key factor is the genotype-phenotype map. With
      the exception of RNA folding, not much is known about the exact nature of this
      mapping. Here, we show that structure of the genotype-phenotype map of simple
      feed-forward circuits is very close to the ones found in RNA; they have a large
      degree of neutrality, by which a circuit can be completely rewired keeping its
      input-output function intact, and there is a relatively small neighbourhood of a
      given circuit containing almost all the phenotypes.

PMID- 17015295
TI  - Colloidal lithography and current fabrication techniques producing in-plane
      nanotopography for biological applications.
AB  - Substrate topography plays a vital role in cell and tissue structure and function
      in situ, where nanometric features, for example, the detail on single collagen
      fibrils, influence cell behaviour and resultant tissue formation. In vitro
      investigations demonstrate that nanotopography can be used to control cell
      reactions to a material surface, indicating its potential application in tissue
      engineering and implant fabrication. Developments in the catalyst, optical,
      medical and electronics industries have resulted in the production of
      nanopatterned surfaces using a variety of methods. The general protocols for
      nanomanufacturing require high resolution and low cost for fabricating devices.
      With respect to biological investigations, nanotopographies should occur across a
      large surface area (ensuring repeatability of experiments and patterning of
      implant surfaces), be reproducible (allowing for consistency in experiments), and
      preferably, accessible (limiting the requirement for specialist equipment).
      Colloidal lithography techniques fit these criteria, where nanoparticles can be
      utilized in combination with a functionalized substrate to produce in-plane
      nanotopographies. Subsequent lithographic processing of colloidal substrates
      utilizing, for example, reactive ion etching allows the production of modified
      colloidal-derived nanotopographies. In addition to two-dimensional in-plane
      nanofabrication, functionalized structures can be dip coated in colloidal sols,
      imparting nanotopographical cues to cells within a three-dimensional environment.

PMID- 17015296
TI  - Biological tolerance of different materials in bulk and nanoparticulate form in a
      rat model: sarcoma development by nanoparticles.
AB  - In order to study the pathobiological impact of the nanometre-scale of materials,
      we evaluated the effects of five different materials as nanoparticulate
      biomaterials in comparison with bulk samples in contact with living tissues. Five
      groups out of 10 rats were implanted bilaterally for up to 12 months with
      materials of the same type, namely TiO2, SiO2, Ni, Co and polyvinyl chloride
      (PVC), subcutaneously with bulk material on one side of the vertebral column and
      intramuscularly with nanoparticulate material on the contralateral side. At the
      end of each implantation time, the site was macroscopically examined, followed by
      histological processing according to standard techniques. Malignant mesenchymal
      tumours (pleomorphic sarcomas) were obtained in five out of six cases of
      implanted Co nanoparticle sites, while a preneoplastic lesion was observed in an
      animal implanted with Co in bulk form. In the Ni group, all animals rapidly
      developed visible nodules at the implanted sites between 4 and 6 months, which
      were diagnosed as rhabdomyosarcomas. Since the ratio of surface area to volume
      did not show significant differences between the Ni/Co group and the
      TiO2/SiO2/PVC group, we suggested that the induction of neoplasia was not
      mediated by physical effects, but was mediated by the well-known carcinogenic
      impact of Ni and Co. The data from the Co group show that the physical properties
      (particulate versus bulk form) could have a significant influence on the
      acceleration of the neoplastic process.

PMID- 17015297
TI  - Bioactive and bioresorbable cellular cubic-composite scaffolds for use in bone
      reconstruction.
AB  - We used a novel composite fibre-precipitation method to create bioactive and
      bioresorbable cellular cubic composites containing calcium phosphate (CaP)
      particles (unsintered and uncalcined hydroxyapatite (u-HA), alpha-tricalcium
      phosphate, beta-tricalcium phosphate, tetracalcium phosphate, dicalcium phosphate
      dihydrate, dicalcium phosphate anhydrate or octacalcium phosphate) in a poly-D/L
      lactide matrix. The CaP particles occupied greater than or equal to 70 wt%
      (greater than or equal to 50 vol%) fractions within the composites. The
      porosities of the cellular cubic composites were greater than or equal to 70% and
      interconnective pores accounted for greater than or equal to 70% of these values.
      In vitro changes in the cellular geometries and physical properties of the
      composites were evaluated over time. The Alamar Blue assay was used to measure
      osteoblast proliferation, while the alkaline phosphatase assay was used to
      measure osteoblast differentiation. Cellular cubic C-u-HA70, which contained 70
      wt% u-HA particles in a 30 wt% poly-D/L-lactide matrix, showed the greatest three
      dimensional cell affinity among the materials tested. This composite had similar
      compressive strength and cellular geometry to cancellous bone, could be modified
      intraoperatively (by trimming or heating) and was able to form cortico-cancellous
      bone-like hybrids. The osteoinductivity of C-u-HA70, independent of biological
      growth factors, was confirmed by implantation into the back muscles of beagles.
      Our results demonstrated that C-u-HA70 has the potential as a cell scaffold or
      temporary hard-tissue substitute for clinical use in bone reconstruction.

PMID- 17015298
TI  - Factors determining the potential for onward transmission of variant Creutzfeldt
      Jakob disease via surgical instruments.
AB  - While the number of variant Creutzfeldt-Jakob disease (vCJD) cases continues to
      decline, concern has been raised that transmission could occur directly from one
      person to another through routes including the transfer of blood and shared use
      of surgical instruments. Here we firstly present data on the surgical procedures
      undertaken on vCJD patients prior to onset of clinical symptoms, which supports
      the hypothesis that cases via this route are possible. We then apply a
      mathematical framework to assess the potential for self-sustaining epidemics via
      surgical procedures. Data from hospital episode statistics on the rates of high-
      and medium-risk procedures in the UK were used to estimate model parameters, and
      sensitivity to other unknown parameters about surgically transmitted vCJD was
      assessed. Our results demonstrate that a key uncertainty determining the scale of
      an epidemic and whether it is self-sustaining is the number of times a single
      instrument is re-used, alongside the infectivity of contaminated instruments and
      the effectiveness of cleaning. A survey into the frequency of re-use of surgical
      instruments would help reduce these uncertainties.

PMID- 17015299
TI  - An entropic characterization of protein interaction networks and cellular
      robustness.
AB  - The structure of molecular networks is believed to determine important aspects of
      their cellular function, such as the organismal resilience against random
      perturbations. Ultimately, however, cellular behaviour is determined by the
      dynamical processes, which are constrained by network topology. The present work
      is based on a fundamental relation from dynamical systems theory, which states
      that the macroscopic resilience of a steady state is correlated with the
      uncertainty in the underlying microscopic processes, a property that can be
      measured by entropy. Here, we use recent network data from large-scale protein
      interaction screens to characterize the diversity of possible pathways in terms
      of network entropy. This measure has its origin in statistical mechanics and
      amounts to a global characterization of both structural and dynamical resilience
      in terms of microscopic elements. We demonstrate how this approach can be used to
      rank network elements according to their contribution to network entropy and also
      investigate how this suggested ranking reflects on the functional data provided
      by gene knockouts and RNAi experiments in yeast and Caenorhabditis elegans. Our
      analysis shows that knockouts of proteins with large contribution to network
      entropy are preferentially lethal. This observation is robust with respect to
      several possible errors and biases in the experimental data. It underscores the
      significance of entropy as a fundamental invariant of the dynamical system, and
      as a measure of structural and dynamical properties of networks. Our analytical
      approach goes beyond the phenomenological studies of cellular robustness based on
      local network observables, such as connectivity. One of its principal
      achievements is to provide a rationale to study proxies of cellular resilience
      and rank proteins according to their importance within the global network
      context.

PMID- 17015301
TI  - Modelling and rapid simulation of multiple red blood cell light scattering.
AB  - The goal of this work is to develop a computational framework to rapidly simulate
      the light scattering response of multiple red blood cells. Because the wavelength
      of visible light (3.8 x 10(-7) m < or = lambda < or = 7.2 x 10(-7) m) is
      approximately an order of magnitude smaller than the diameter of a typical red
      blood cell scatterer (d approximately 8 x 10(-6) m), geometric ray-tracing theory
      is applicable, and can be used to quickly ascertain the amount of optical energy,
      characterized by the Poynting vector, that is reflected and absorbed by multiple
      red blood cells. The overall objective is to provide a straightforward approach
      that can be easily implemented by researchers in the field, using standard
      desktop computers. Three-dimensional examples are given to illustrate the
      approach and the results compare quite closely to experiments on blood samples
      conducted at the Children's Hospital Oakland Research Institute (CHORI).

PMID- 17015300
TI  - Biomechanics of the cardiovascular system: the aorta as an illustratory example.
AB  - Biomechanics relates the function of a physiological system to its structure. The
      objective of biomechanics is to deduce the function of a system from its
      geometry, material properties and boundary conditions based on the balance laws
      of mechanics (e.g. conservation of mass, momentum and energy). In the present
      review, we shall outline the general approach of biomechanics. As this is an
      enormously broad field, we shall consider a detailed biomechanical analysis of
      the aorta as an illustration. Specifically, we will consider the geometry and
      material properties of the aorta in conjunction with appropriate boundary
      conditions to formulate and solve several well-posed boundary value problems.
      Among other issues, we shall consider the effect of longitudinal pre-stretch and
      surrounding tissue on the mechanical status of the vessel wall. The solutions of
      the boundary value problems predict the presence of mechanical homeostasis in the
      vessel wall. The implications of mechanical homeostasis on growth, remodelling
      and postnatal development of the aorta are considered.

PMID- 17015302
TI  - Polypyrrole-based conducting polymers and interactions with biological tissues.
AB  - Polypyrrole (PPy) is a conjugated polymer that displays particular electronic
      properties including conductivity. In biomedical applications, it is usually
      electrochemically generated with the incorporation of any anionic species
      including also negatively charged biological macromolecules such as proteins and
      polysaccharides to give composite materials. In biomedical research, it has
      mainly been assessed for its role as a reporting interface in biosensors.
      However, there is an increasing literature on the application of PPy as a
      potentially electrically addressable tissue/cell support substrate. Here, we
      review studies that have considered such PPy based conducting polymers in direct
      contact with biological tissues and conclude that due to its versatile functional
      properties, it could contribute to a new generation of biomaterials.

PMID- 17015303
TI  - Magnetic iron compounds in the human brain: a comparison of tumour and
      hippocampal tissue.
AB  - Iron is a central element in the metabolism of normal and malignant cells.
      Abnormalities in iron and ferritin expression have been observed in many types of
      cancer. Interest in characterizing iron compounds in the human brain has
      increased due to advances in determining a relationship between excess iron
      accumulation and neurological and neurodegenerative diseases. In this work, four
      different magnetic methods have been employed to characterize the iron phases and
      magnetic properties of brain tumour (meningiomas) tissues and non-tumour
      hippocampal tissues. Four main magnetic components can be distinguished: the
      diamagnetic matrix, nearly paramagnetic blood, antiferromagnetic ferrihydrite
      cores of ferritin and ferrimagnetic magnetite and/or maghemite. For the first
      time, open hysteresis loops have been observed on human brain tissue at room
      temperature. The hysteresis properties indicate the presence of magnetite and/or
      maghemite particles that exhibit stable single-domain (SD) behaviour at room
      temperature. A significantly higher concentration of magnetically ordered
      magnetite and/or maghemite and a higher estimated concentration of heme iron was
      found in the meningioma samples. First-order reversal curve diagrams on
      meningioma tissue further show that the stable SD particles are magnetostatically
      interacting, implying high-local concentrations (clustering) of these particles
      in brain tumours. These findings suggest that brain tumour tissue contains an
      elevated amount of remanent iron oxide phases.

PMID- 17015304
TI  - Automated tracking of gene expression in individual cells and cell compartments.
AB  - Many intracellular signal transduction processes involve the reversible
      translocation from the cytoplasm to the nucleus of transcription factors. The
      advent of fluorescently tagged protein derivatives has revolutionized cell
      biology, such that it is now possible to follow the location of such protein
      molecules in individual cells in real time. However, the quantitative analysis of
      the location of such proteins in microscopic images is very time consuming. We
      describe CellTracker, a software tool designed for the automated measurement of
      the cellular location and intensity of fluorescently tagged proteins. CellTracker
      runs in the MS Windows environment, is freely available (at
      http://www.dbkgroup.org/celltracker/), and combines automated cell tracking
      methods with powerful image-processing algorithms that are optimized for these
      applications. When tested in an application involving the nuclear transcription
      factor NF-kappaB, CellTracker is competitive in accuracy with the manual human
      analysis of such images but is more than 20 times faster, even on a small task
      where human fatigue is not an issue. This will lead to substantial benefits for
      time-lapse-based high-content screening.

PMID- 17015305
TI  - An ontology of scientific experiments.
AB  - The formal description of experiments for efficient analysis, annotation and
      sharing of results is a fundamental part of the practice of science. Ontologies
      are required to achieve this objective. A few subject-specific ontologies of
      experiments currently exist. However, despite the unity of scientific
      experimentation, no general ontology of experiments exists. We propose the
      ontology EXPO to meet this need. EXPO links the SUMO (the Suggested Upper Merged
      Ontology) with subject-specific ontologies of experiments by formalizing the
      generic concepts of experimental design, methodology and results representation.
      EXPO is expressed in the W3C standard ontology language OWL-DL. We demonstrate
      the utility of EXPO and its ability to describe different experimental domains,
      by applying it to two experiments: one in high-energy physics and the other in
      phylogenetics. The use of EXPO made the goals and structure of these experiments
      more explicit, revealed ambiguities, and highlighted an unexpected similarity. We
      conclude that, EXPO is of general value in describing experiments and a step
      towards the formalization of science.

PMID- 17015306
TI  - Evolutionary transitions and mechanisms of matte and iridescent plumage
      coloration in grackles and allies (Icteridae).
AB  - Iridescent structural colour is found in a wide variety of organisms. In birds,
      the mechanisms that create these colours are diverse, but all are based on
      ordered arrays of melanin granules within a keratin substrate in barbules. The
      feathers of the grackles and allies in the family Icteridae range in appearance
      from matte black to iridescent. In a phylogenetic analysis of this clade, we
      identified several evolutionary transitions between these colour states. To
      describe a possible mechanistic explanation for the lability of plumage
      coloration, we used spectrometry, transmission electron microscopy and thin-film
      optical modelling of the feathers of 10 icterid species from five genera,
      including taxa with matte black or iridescent feathers. In matte black species,
      melanin was densely packed in barbules, while in iridescent species, melanin
      granules were arranged in ordered layers around the edges of barbules. The
      structured arrangement of melanin granules in iridescent species created optical
      interfaces, which are shown by our optical models to be critical for iridescent
      colour production by coherent scattering. These data imply that rearrangement of
      melanin granules in barbules is a mechanism for shifts between black and
      iridescent colours, and that the relative simplicity of this mechanism may
      explain the lability of plumage colour state within this group.

PMID- 17015307
TI  - Orthogonal (transverse) arrangements of actin in endothelia and fibroblasts.
AB  - Though actin filaments running across the cell (transverse actin) have been
      occasionally reported for epithelial cells in groups and for cells growing on
      fibres, there has been no report heretofore of transverse actin in cells grown on
      planar substrata. This paper describes evidence in support of this possibility
      derived from actin staining, polarization microscopy and force measurements. The
      paper introduces two new methods for detecting the orientation and activity of
      contractile elements in cells. The orthogonal actin is most obvious in cells
      grown on groove ridge structures, but can be detected in cells grown on flat
      surfaces.

PMID- 17015308
TI  - A bizarre new toothed mysticete (Cetacea) from Australia and the early evolution
      of baleen whales.
AB  - Extant baleen whales (Cetacea, Mysticeti) are all large filter-feeding marine
      mammals that lack teeth as adults, instead possessing baleen, and feed on small
      marine animals in bulk. The early evolution of these superlative mammals, and
      their unique feeding method, has hitherto remained enigmatic. Here, I report a
      new toothed mysticete from the Late Oligocene of Australia that is more archaic
      than any previously described. Unlike all other mysticetes, this new whale was
      small, had enormous eyes and lacked derived adaptations for bulk filter-feeding.
      Several morphological features suggest that this mysticete was a macrophagous
      predator, being convergent on some Mesozoic marine reptiles and the extant
      leopard seal (Hydrurga leptonyx). It thus refutes the notions that all stem
      mysticetes were filter-feeders, and that the origins and initial radiation of
      mysticetes was linked to the evolution of filter-feeding. Mysticetes evidently
      radiated into a variety of disparate forms and feeding ecologies before the
      evolution of baleen or filter-feeding. The phylogenetic context of the new whale
      indicates that basal mysticetes were macrophagous predators that did not employ
      filter-feeding or echolocation, and that the evolution of characters associated
      with bulk filter-feeding was gradual.

PMID- 17015309
TI  - Environmental forcing as a main determinant of bloom dynamics of the
      Chrysochromulina algae.
AB  - In this paper, we demonstrate that the seasonal dynamics in the abiotic factors,
      without including seasonal changes in the biological relationships, can
      appropriately account for the seasonal dynamics of Chrysochromulina spp. This is
      through the analysis of data on the population dynamics of Chrysochromulina spp.
      off southern Norway that is evaluated in relation to environmental factors and
      season by the analyses of 12 year monthly time-series. Chrysochromulina spp.
      abundance, nutrient concentrations, hydrographical properties, as well as current
      and wind data were analysed on a monthly scale by means of autoregressive moving
      average models, principal component analyses (PCA), and linear and nonlinear
      regression models. Seasonal development of the Chrysochromulina assemblage was
      well predicted from regression models forced with two PCA components representing
      seasonal variation in nutrient and chlorophyll a levels and ratios, inflow of
      North Seawater to the Skagerrak and northeasterly wind along the Norwegian coast.
      Assuming these to be general results, we might hypothesis that marine algal
      communities are governed by seasonally varying abiotic factors to a large extent.

PMID- 17015310
TI  - Invasion of an asexual American water flea clone throughout Africa and rapid
      displacement of a native sibling species.
AB  - The huge ecological and economic impact of biological invasions creates an urgent
      need for knowledge of traits that make invading species successful and factors
      helping indigenous populations to resist displacement by invading species or
      genotypes. High genetic diversity is generally considered to be advantageous in
      both processes. Combined with sex, it allows rapid evolution and adaptation to
      changing environments. We combined paleogenetic analysis with continent-wide
      survey of genetic diversity at nuclear and mitochondrial loci to reconstruct the
      invasion history of a single asexual American water flea clone (hybrid Daphnia
      pulexxDaphnia pulicaria) in Africa. Within 60 years of the original introduction
      of this invader, it displaced the genetically diverse, sexual population of
      native D. pulex in Lake Naivasha (Kenya), despite a formidable numerical
      advantage of the local population and continuous replenishment from a large
      dormant egg bank. Currently, the invading clone has spread throughout the range
      of native African D. pulex, where it appears to be the only occurring genotype.
      The absence of genetic variation did not hamper either the continent-wide
      establishment of this exotic lineage or the effective displacement of an
      indigenous and genetically diverse sibling species.

PMID- 17015312
TI  - Compliant leg behaviour explains basic dynamics of walking and running.
AB  - The basic mechanics of human locomotion are associated with vaulting over stiff
      legs in walking and rebounding on compliant legs in running. However, while
      rebounding legs well explain the stance dynamics of running, stiff legs cannot
      reproduce that of walking. With a simple bipedal spring-mass model, we show that
      not stiff but compliant legs are essential to obtain the basic walking mechanics;
      incorporating the double support as an essential part of the walking motion, the
      model reproduces the characteristic stance dynamics that result in the observed
      small vertical oscillation of the body and the observed out-of-phase changes in
      forward kinetic and gravitational potential energies. Exploring the parameter
      space of this model, we further show that it not only combines the basic dynamics
      of walking and running in one mechanical system, but also reveals these gaits to
      be just two out of the many solutions to legged locomotion offered by compliant
      leg behaviour and accessed by energy or speed.

PMID- 17015311
TI  - Do distantly related parasites rely on the same proximate factors to alter the
      behaviour of their hosts?
AB  - Phylogenetically unrelated parasites often increase the chances of their
      transmission by inducing similar phenotypic changes in their hosts. However, it
      is not known whether these convergent strategies rely on the same biochemical
      precursors. In this paper, we explored such aspects by studying two gammarid
      species (Gammarus insensibilis and Gammarus pulex; Crustacea: Amphipoda:
      Gammaridae) serving as intermediate hosts in the life cycle of two distantly
      related parasites: the trematode, Microphallus papillorobustus and the
      acanthocephalan, Polymorphus minutus. Both these parasite species are known to
      manipulate the behaviour of their amphipod hosts, bringing them towards the water
      surface, where they are preferentially eaten by aquatic birds (definitive hosts).
      By studying and comparing the brains of infected G. insensibilis and G. pulex
      with proteomics tools, we have elucidated some of the proximate causes involved
      in the parasite-induced alterations of host behaviour for each system. Protein
      identifications suggest that altered physiological compartments in hosts can be
      similar (e.g. immunoneural connexions) or different (e.g. vision process), and
      hence specific to the host-parasite association considered. Moreover, proteins
      required to alter the same physiological compartment can be specific or
      conversely common in both systems, illustrating in the latter case a molecular
      convergence in the proximate mechanisms of manipulation.

PMID- 17015313
TI  - Seasonal plankton dynamics along a cross-shelf gradient.
AB  - Much interest has recently been devoted to reconstructing the dynamic structure
      of ecological systems on the basis of time-series data. Using 10 years of monthly
      data on phyto- and zooplankton abundance from the Bay of Biscay (coastal to shelf
      break sites), we demonstrate that the interaction between these two plankton
      components is approximately linear, whereas the effects of environmental factors
      (nutrients, temperature, upwelling and photoperiod) on these two plankton
      population growth rates are nonlinear. With the inclusion of the environmental
      factors, the main observed seasonal and inter-annual dynamic patterns within the
      studied plankton assemblage also indicate the prevalence of bottom-up regulatory
      control.

PMID- 17015314
TI  - Sex-specific foraging strategies and resource partitioning in the southern
      elephant seal (Mirounga leonina).
AB  - The evolution of resource specializations is poorly understood, especially in
      marine systems. The southern elephant seal (Mirounga leonina) is the largest of
      the phocid seals, sexually dimorphic, and thought to prey predominantly on fish
      and squid. We collected vibrissae from male and female southern elephant seals,
      and assessed stable C and N isotope ratios along the length of the vibrissae.
      Given that whiskers grow slowly, this sampling strategy reflects any variation in
      feeding behaviour over a period of time. We found that isotopic variation among
      females was relatively small, and that the apparent prey choice and trophic level
      of females was different from that for males. Further, males showed a very broad
      range of trophic/prey choice positions, grouped into several clusters, and this
      included isotopic values too low to match a broad range of potential fish and
      cephalopod prey tested. One of these clusters overlapped with data for South
      American sea lions (Otaria flavescens), which were measured for comparison. Both
      male southern elephant seals and southern sea lions forage over the continental
      shelf, providing the potential for competition. We discuss the possibility that
      individual southern elephant seals are pursuing specialist foraging strategies to
      avoid competition, both with one another, and with the South American sea lions
      that breed nearby.

PMID- 17015315
TI  - Volatile emission by contest losers revealed by real-time chemical analysis.
AB  - Animal interactions often involve chemical exchange but simultaneous evaluation
      of chemistry and behaviour has been problematical. Here we report findings from a
      novel method, atmospheric pressure chemical ionization-mass spectrometry (APCI
      MS) coupled with manipulation of molecular-mass achieved by rearing organisms on
      deuterium-enhanced nutrients. This allows real-time monitoring of the occurrence
      and quantity of volatile chemicals released by each of two interacting
      individuals, in tandem with behavioural observations. We apply these methods to
      female-female contests in the parasitoid wasp Goniozus legneri. We show that this
      species emits the spiroacetal 2-methyl-1,7-dioxaspiro[5.5]undecane. Chemical
      release is most common in more behaviourally aggressive contests, which occur
      when prior resource owners successfully resist take-over by similar-sized
      intruder females. Volatiles released during contests are always emitted by the
      loser. Aggression in contests is reduced after spiroacetal release. We suggest
      that the spiroacetal functions as a weapon of rearguard action. We anticipate
      that APCI-MS, which is rapid, non-intrusive and relatively inexpensive to
      operate, will be widely applied in studies linking chemistry and behaviour.

PMID- 17015316
TI  - Bird navigation: what type of information does the magnetite-based receptor
      provide?
AB  - Previous experiments have shown that a short, strong magnetic pulse caused
      migratory birds to change their headings from their normal migratory direction to
      an easterly direction in both spring and autumn. In order to analyse the nature
      of this pulse effect, we subjected migratory Australian silvereyes, Zosterops
      lateralis, to a magnetic pulse and tested their subsequent response under
      different magnetic conditions. In the local geomagnetic field, the birds
      preferred easterly headings as before, and when the horizontal component of the
      magnetic field was shifted 90 degrees anticlockwise, they altered their headings
      accordingly northwards. In a field with the vertical component inverted, the
      birds reversed their headings to westwards, indicating that their directional
      orientation was controlled by the normal inclination compass. These findings show
      that although the pulse strongly affects the magnetite particles, it leaves the
      functional mechanism of the magnetic compass intact. Thus, magnetite-based
      receptors seem to mediate magnetic 'map'-information used to determine position,
      and when affected by a pulse, they provide birds with false positional
      information that causes them to change their course.

PMID- 17015317
TI  - Pharmacodynamics of non-replicating viruses, bacteriocins and lysins.
AB  - The pharmacodynamics of antibiotics and many other chemotherapeutic agents is
      often governed by a 'multi-hit' kinetics, which requires the binding of several
      molecules of the therapeutic agent for the killing of their targets. In contrast,
      the pharmacodynamics of novel alternative therapeutic agents, such as phages and
      bacteriocins against bacterial infections or viruses engineered to target tumour
      cells, is governed by a 'single-hit' kinetics according to which the agent will
      kill once it is bound to its target. In addition to requiring only a single
      molecule for killing, these agents bind irreversibly to their targets. Here, we
      explore the pharmacodynamics of such 'irreversible, single-hit inhibitors' using
      mathematical models. We focus on agents that do not replicate, i.e. in the case
      of phage therapy, we deal only with non-lytic phages and in the case of cancer
      treatment, we restrict our analysis to replication of incompetent viruses. We
      study the impact of adsorption on dead cells, heterogeneity in adsorption rates
      and spatial compartmentalization.

PMID- 17015318
TI  - Himalayan porter's specialization: metabolic power, economy, efficiency and
      skill.
AB  - Carrying heavy loads in the Himalayan region is a real challenge. Porters face
      extreme ranges in terrain condition, path steepness, altitude hypoxia and climate
      for 6-8h a day, many months a year, since they were boys. It has been previously
      shown that, when carrying loads on level terrain, porters' metabolic economy is
      higher than in Caucasians but the reasons are still unknown. We monitored
      Nepalese porters both during 90 km trekking in Khumbu Valley and at two different
      altitudes (3490 and 5050 m above sea-level), where they were compared to
      Caucasian mountaineers during (22%) gradient walking. Both subject groups carried
      a load of up to 90% body mass. The remarkably higher performance of porters
      during uphill locomotion (+60% in speed, +39% mechanical power) is only partly
      explained by the lower cost of loaded walking (-20%), being also the result of a
      better cardio-circulatory adaptation to altitude, which generates a higher mass
      specific metabolic power (+30%). Consequently, Nepalese porters show higher
      efficiency, both during uphill and downhill loaded walking. Their higher economy
      on steep paths cannot be ascribed to a better exchange between potential and
      kinetic energy, as in our experiments the body centre of mass travelled
      monotonically uphill (or downhill). A different oscillation pattern of the loaded
      head-trunk segment, together with the analysis of the different components of the
      mechanical work during load carrying, suggests that achieved motor skills in
      balancing the loaded body segment above the hip could play a role in determining
      the better economy of porters.

PMID- 17015319
TI  - Locating the barnacle settlement pheromone: spatial and ontogenetic expression of
      the settlement-inducing protein complex of Balanus amphitrite.
AB  - Barnacles are prominent members of hard substratum benthic communities and their
      study has been important to advances in experimental ecology and contemporary
      ecological theory. Having recently characterized the cue to gregarious settlement
      of Balanus amphitrite, the settlement-inducing protein complex (SIPC), we use two
      polyclonal antibodies to examine the tissue distribution and ontogenetic
      expression of this glycoprotein. These antibodies were raised against two
      separate peptides located near the N- and C-termini of the SIPC and were used to
      detect the glycoprotein by western blotting and immunohistochemistry. By in situ
      hybridization we also show that the SIPC mRNA co-occurs with the expressed
      glycoprotein in the cuticles of both nauplius and cypris larval stages and the
      adult. In the larvae, the SIPC is expressed most strongly in the mouthparts and
      the hindgut of the stage 2 nauplius and in the thoracopods, antennules and
      bivalved carapace of the cyprid. In adult B. amphitrite, the expressed SIPC is
      present in protein extracts of the shell and in all organs that are lined by
      cuticular tissues. We suggest that the SIPC is produced by the epidermal cells
      that secrete the cuticle and discuss these observations with regard to earlier
      studies and the role of the SIPC as a contact pheromone.

PMID- 17015320
TI  - Modelling the initial spread of foot-and-mouth disease through animal movements.
AB  - Livestock movements in Great Britain (GB) are well recorded and are a unique
      record of the network of connections among livestock-holding locations. These
      connections can be critical for disease spread, as in the 2001 epidemic of foot
      and-mouth disease (FMD) in the UK. Here, the movement data are used to construct
      an individual-farm-based model of the initial spread of FMD in GB and determine
      the susceptibility of the GB livestock industry to future outbreaks under the
      current legislative requirements. Transmission through movements is modelled,
      with additional local spread unrelated to the known movements. Simulations show
      that movements can result in a large nationwide epidemic, but only if cattle are
      heavily involved, or the epidemic occurs in late summer or early autumn.
      Inclusion of random local spread can considerably increase epidemic size, but has
      only a small impact on the spatial extent of the disease. There is a geographical
      bias in the epidemic size reached, with larger epidemics originating in Scotland
      and the north of England than elsewhere.

PMID- 17015321
TI  - Rapid adaptation of insect herbivores to an invasive plant.
AB  - Introduced plant success often is attributed to release from natural enemies in
      their new ranges. However, herbivores may accumulate over time and reduce
      invasiveness but evidence for this process to date is weak. We report here that
      enemy release is indeed limited to the early stages of introduction of the
      Chinese tallow tree (Sapium sebiferum). In bioassays and gardens along a
      geographical gradient of time since tallow tree introduction, herbivory was
      highest and tree performance was poorest where tallow tree has been present
      longer (i.e. introduced earlier). Additionally, Asian ecotypes (grown from seeds
      collected in Asia) had lower survival than North American ecotypes (seeds
      collected in North America), which is consistent with genetic responses to low
      herbivory in the introduced range (EICA Hypothesis). Release from insect
      herbivores appears to contribute to early success of the tallow tree, but
      accumulation of insect herbivores has apparently reduced this benefit over time.

PMID- 17015322
TI  - Major cranial changes during Triceratops ontogeny.
AB  - This is the first cranial ontogenetic assessment of Triceratops, the well-known
      Late Cretaceous dinosaur distinguished by three horns and a massive parietal
      squamosal frill. Our analysis is based on a growth series of 10 skulls, ranging
      from a 38 cm long baby skull to about 2 m long adult skulls. Four growth stages
      correspond to a suite of ontogenetic characters expressed in the postorbital
      horns, frill, nasal, epinasal horn and epoccipitals. Postorbital horns are
      straight stubs in early ontogeny, curve posteriorly in juveniles, straighten in
      subadults and recurve anteriorly in adults. The posterior margin of the baby
      frill is deeply scalloped. In early juveniles, the frill margin becomes
      ornamented by 17-19 delta-shaped epoccipitals. Epoccipitals are dorsoventrally
      compressed in subadults, strongly compressed and elongated in adults and
      ultimately merge onto the posterior frill margin in older adults. Ontogenetic
      trends within and between growth stages include: posterior frill margin
      transitions from scalloped to wavy and smooth; progressive exclusion of the
      supraoccipital from the foramen magnum; internal hollowing at the base of the
      postorbital horns; closure of the midline nasal suture; fusion of the epinasal
      onto the nasals; and epinasal expansion into a morphologically variable nasal
      horn. We hypothesize that the changes in horn orientation and epoccipital shape
      function to allow visual identity of juveniles, and signal their attainment of
      sexual maturity.

PMID- 17015323
TI  - Can the common brain parasite, Toxoplasma gondii, influence human culture?
AB  - The latent prevalence of a long-lived and common brain parasite, Toxoplasma
      gondii, explains a statistically significant portion of the variance in aggregate
      neuroticism among populations, as well as in the 'neurotic' cultural dimensions
      of sex roles and uncertainty avoidance. Spurious or non-causal correlations
      between aggregate personality and aspects of climate and culture that influence
      T. gondii transmission could also drive these patterns. A link between culture
      and T. gondii hypothetically results from a behavioural manipulation that the
      parasite uses to increase its transmission to the next host in the life cycle: a
      cat. While latent toxoplasmosis is usually benign, the parasite's subtle effect
      on individual personality appears to alter the aggregate personality at the
      population level. Drivers of the geographical variation in the prevalence of this
      parasite include the effects of climate on the persistence of infectious stages
      in soil, the cultural practices of food preparation and cats as pets. Some
      variation in culture, therefore, may ultimately be related to how climate affects
      the distribution of T. gondii, though the results only explain a fraction of the
      variation in two of the four cultural dimensions, suggesting that if T. gondii
      does influence human culture, it is only one among many factors.

PMID- 17015324
TI  - Network frailty and the geometry of herd immunity.
AB  - The spread of infectious disease through communities depends fundamentally on the
      underlying patterns of contacts between individuals. Generally, the more contacts
      one individual has, the more vulnerable they are to infection during an epidemic.
      Thus, outbreaks disproportionately impact the most highly connected demographics.
      Epidemics can then lead, through immunization or removal of individuals, to
      sparser networks that are more resistant to future transmission of a given
      disease. Using several classes of contact networks-Poisson, scale-free and small
      world-we characterize the structural evolution of a network due to an epidemic in
      terms of frailty (the degree to which highly connected individuals are more
      vulnerable to infection) and interference (the extent to which the epidemic cuts
      off connectivity among the susceptible population that remains following an
      epidemic). The evolution of the susceptible network over the course of an
      epidemic differs among the classes of networks; frailty, relative to
      interference, accounts for an increasing component of network evolution on
      networks with greater variance in contacts. The result is that immunization due
      to prior epidemics can provide greater community protection than random
      vaccination on networks with heterogeneous contact patterns, while the reverse is
      true for highly structured populations.

PMID- 17015325
TI  - The organic preservation of fossil arthropods: an experimental study.
AB  - Modern arthropod cuticles consist of chitin fibres in a protein matrix, but those
      of fossil arthropods with an organic exoskeleton, particularly older than
      Tertiary, contain a dominant aliphatic component. This apparent contradiction was
      examined by subjecting modern cockroach, scorpion and shrimp cuticle to
      artificial maturation (350 degrees C/700 bars/24 h) following various chemical
      treatments, and analysing the products with pyrolysis-gas chromatography/mass
      spectrometry (Py-GC/MS). Analysis of artificially matured untreated cuticle
      yielded moieties related to phenols and alkylated substituents, pyridines,
      pyrroles and possibly indenes (derived from chitin). n-Alkyl amides, C16 and C18
      fatty acids and alkane/alk-1-ene homologues ranging from C9 to C19 were also
      generated, the last indicating the presence of an n-alkyl component, similar in
      composition to that encountered in fossil arthropods. Similar pyrolysates were
      obtained from matured pure C16 and C18 fatty acids. Py-GC/MS of cuticles matured
      after lipid extraction and hydrolysis did not yield any aliphatic polymer. This
      provides direct experimental evidence that lipids incorporated from the cuticle
      were the source of aliphatic polymer. This process of in situ polymerization
      appears to account for most of the fossil record of terrestrial arthropods as
      well as marine arthropods that lacked a biomineralized exoskeleton.

PMID- 17015326
TI  - Maternal antibodies postpone hantavirus infection and enhance individual breeding
      success.
AB  - The transfer of maternal antibodies from mother to progeny is a well-known
      phenomenon in avian and mammalian species. Optimally, they protect the newborn
      against the pathogens in the environment. The effect of maternal antibodies on
      microparasite transmission dynamics may have important consequences for both the
      fitness of the host and the epizootic processes of the pathogens. However, there
      is a scarcity of studies examining these effects in free-living wild species. We
      studied the influence of maternal antibodies against the zoonotic Puumala
      hantavirus (PUUV) on the fitness of bank voles (Clethrionomys glareolus) and on
      PUUV transmission by exposing young maternal antibody-positive (MatAb+) and
      negative (MatAb-) bank voles (n=160) to PUUV in experimental populations. PUUV
      specific maternal antibodies delayed the timing of infection. Females were more
      susceptible to PUUV infection than males. Interestingly, both the females and the
      males with maternal antibodies matured earlier than the other individuals in the
      population. Our results highlight the significance of maternal antibodies in the
      transmission of a pathogen and in the breeding success of the carriers.

PMID- 17015327
TI  - Numerical assessment affects aggression and competitive ability: a team-fighting
      strategy for the ant Formica xerophila.
AB  - The relationship between numerical advantage and competitive ability is a
      fundamental component in contests between groups of social animals. An
      individual's ability to correctly assess the numerical state of its group is of
      vital importance. In addition to numerical dominance, the group's fighting
      ability also plays an important role in competitive interactions. By staging
      experimental fights between two Formica ant species, I show that Formica
      xerophila are able to assess their own group's strength prior to any competitive
      encounter. Ants that perceive themselves as part of a large group act more
      aggressively toward a competitor than ants that perceive themselves as isolated
      individuals. This increase in aggression improves F. xerophila's competitive
      ability. Furthermore, the number of individuals in a contest was found to affect
      competitive ability. In contests with equal number of competitors, groups of F.
      xerophila were more successful than individual F. xerophila. Contrary to previous
      predictions using Lanchester's laws of fighting, F. xerophila's ability to kill
      competitors increased nonlinearly with group size. This nonlinearity was due to
      the collective fighting strategy of an F. xerophila group isolating and engaging
      a single Formica integroides competitors.

PMID- 17015328
TI  - Group decision making in fission-fusion societies: evidence from two-field
      experiments in Bechstein's bats.
AB  - Group decisions are required when group coordination is beneficial, but
      individuals can choose between alternatives. Despite the increased interest in
      animal group decision making, there is a lack of experimental field studies that
      investigate how animals with conflicting information make group decisions. In
      particular, no field studies have considered the influence of fission-fusion
      behaviour (temporary splitting into subgroups) on group decisions. We studied
      group decision making in two wild Bechstein's bat colonies, which are fission
      fusion societies of stable individual composition. Since they frequently switch
      communal roosts, colony members must regularly make group decisions over where to
      roost. In the two-field experiments, we provided marked individuals with
      conflicting information about the suitability of potential roosts. We
      investigated whether conflicting information led to group decisions that followed
      a 'unanimous' or a 'majority' rule, or increased colony fission. Individual
      behaviour suggests that bats considered both their own information and the
      behaviour of others when deciding where to roost. Group decisions about communal
      roosts reflected the information available to a majority of the bats roosting
      together, but conflicting information led to an increased fission in one colony.
      Our results suggest that fission-fusion societies allow individuals to avoid
      majority decisions that are not in their favour.

PMID- 17015329
TI  - Responding to environmental change: plastic responses vary little in a
      synchronous breeder.
AB  - The impact of environmental change on animal populations is strongly influenced
      by the ability of individuals to plastically adjust key life-history events.
      There is therefore considerable interest in establishing the degree of plasticity
      in traits and how selection acts on plasticity in natural populations. Breeding
      time is a key life-history trait that affects fitness and recent studies have
      found that females vary significantly in their breeding time-environment
      relationships, with selection often favouring individuals exhibiting stronger
      plastic responses. In contrast, here, we show that although breeding time in the
      common guillemot, Uria aalge, is highly plastic at the population level in
      response to a large-scale environmental cue (the North Atlantic Oscillation,
      NAO), there is very little between-individual variation-most individuals respond
      to this climate cue very similarly. We demonstrate strong stabilizing selection
      against individuals who deviate from the average population-level response to
      NAO. This species differs significantly from those previously studied in being a
      colonial breeder, in which reproductive synchrony has a substantial impact on
      fitness; we suggest that counter selection imposed by a need for synchrony could
      limit individuals in their response and potential for directional selection to
      act. This demonstrates the importance of considering the relative costs and
      benefits of highly plastic responses in assessing the likely response of a
      population to the environmental change.

PMID- 17015330
TI  - Marine animal behaviour: neglecting ocean currents can lead us up the wrong
      track.
AB  - Tracks of marine animals in the wild, now increasingly acquired by electronic
      tagging of individuals, are of prime interest not only to identify habitats and
      high-risk areas, but also to gain detailed information about the behaviour of
      these animals. Using recent satellite-derived current estimates and leatherback
      turtle (Dermochelys coriacea) tracking data, we demonstrate that oceanic
      currents, usually neglected when analysing tracking data, can substantially
      distort the observed trajectories. Consequently, this will affect several
      important results deduced from the analysis of tracking data, such as the
      evaluation of the orientation skills and the energy budget of animals or the
      identification of foraging areas. We conclude that currents should be
      systematically taken into account to ensure the unbiased interpretation of
      tracking data, which now play a major role in marine conservation biology.

PMID- 17015331
TI  - Tooth microstructure tracks the pace of human life-history evolution.
AB  - A number of fundamental milestones define the pace at which animals develop,
      mature, reproduce and age. These include the length of gestation, the age at
      weaning and at sexual maturity, the number of offspring produced over a lifetime
      and the length of life itself. Because a time-scale for dental development can be
      retrieved from the internal structure of teeth and many of these life-history
      variables tend to be highly correlated, we can discover more than might be
      imagined about fossil primates and more, in particular, about fossil hominids and
      our own evolutionary history. Some insights into the evolutionary processes
      underlying changes in dental development are emerging from a better understanding
      of the mechanisms controlling enamel and dentine formation. Our own 18-20-year
      period of growth and development probably evolved quite recently after ca 17
      million years of a more ape-like life-history profile.

PMID- 17015332
TI  - Learning the ecological niche.
AB  - A cornerstone of ecological theory is the ecological niche. Yet little is known
      about how individuals come to adopt it: whether it is innate or learned. Here, we
      report a cross-fostering experiment in the wild where we transferred eggs of blue
      tits, Cyanistes caeruleus, to nests of great tits, Parus major, and vice versa,
      to quantify the consequences of being reared in a different social context, but
      in an environment otherwise natural to the birds. We show that early learning
      causes a shift in the feeding niche in the direction of the foster species and
      that this shift lasts for life (foraging conservatism). Both species changed
      their feeding niches, but the change was greater in the great tit with its less
      specialized feeding behaviour. The study shows that cultural transmission through
      early learning is fundamental to the realization of ecological niches, and
      suggests a mechanism to explain learned habitat preference and sympatric
      speciation in animals.

PMID- 17015333
TI  - Opsin gene duplication and diversification in the guppy, a model for sexual
      selection.
AB  - Identification of genes that control variation in adaptive characters is a
      prerequisite for understanding the processes that drive sexual and natural
      selection. Male coloration and female colour perception play important roles in
      mate choice in the guppy (Poecilia reticulata), a model organism for studies of
      natural and sexual selection. We examined a potential source for the known
      variation in colour perception, by analysing genomic and complementary DNA
      sequences of genes that code for visual pigment proteins. We find high sequence
      variability, both within and between populations, and expanded copy number for
      long-wave sensitive (LWS) opsin genes. Alleles with non-synonymous changes that
      suggest dissimilar spectral tuning properties occur in the same population and
      even in the same individual, and the high frequency of non-synonymous
      substitutions argues for diversifying selection acting on these proteins.
      Therefore, variability in tuning amino acids is partitioned within individuals
      and populations of the guppy, in contrast to variability for LWS at higher
      taxonomic levels in cichlids, a second model system for differentiation owing to
      sexual selection. Since opsin variability parallels the extreme male colour
      polymorphism within guppy populations, we suggest that mate choice has been a
      major factor driving the coevolution of opsins and male ornaments in this
      species.

PMID- 17015334
TI  - From record performance to hypoxia tolerance: respiratory transition in
      damselfish larvae settling on a coral reef.
AB  - The fastest swimming fishes in relation to size are found among coral reef fish
      larvae on their way to settle on reefs. By testing two damselfishes, Chromis
      atripectoralis and Pomacentrus amboinensis, we show that the high swimming speeds
      of the pre-settlement larvae are accompanied by the highest rates of oxygen
      uptake ever recorded in ectothermic vertebrates. As expected, these high rates of
      oxygen uptake occur at the cost of poor hypoxia tolerance. However, hypoxia
      tolerance is needed when coral reef fishes seek nocturnal shelter from predators
      within coral colonies, which can become severely hypoxic microhabitats at night.
      When the larvae settle on the reef, we found that they go through a striking
      respiratory transformation, i.e. the capacity for rapid oxygen uptake falls,
      while the ability for high-affinity oxygen uptake at low oxygen levels is
      increased. This transition to hypoxia tolerance is needed when they settle on the
      reef; this was strengthened by our finding that small resident larvae of
      Acanthochromis polyacanthus, a damselfish lacking a planktonic larval stage, do
      not display such a transition, being well adapted to hypoxia and showing
      relatively low maximum rates of oxygen uptake that change little with age.

PMID- 17015335
TI  - How does resource supply affect evolutionary diversification?
AB  - The availability of different resources in the environment can affect the
      outcomes of evolutionary diversification. A unimodal distribution of diversity
      with resource supply has been widely observed and explained previously in the
      context of selection acting in a spatially heterogeneous environment. Here, we
      propose an alternative mechanism to explain the relationship between resource
      supply and diversification that is based on selection for exploitation of
      different resources. To test this mechanism, we conducted a selection experiment
      using the bacterium Pseudomonas fluorescens in spatially homogeneous environments
      over a wide range of resource supply rates. Our results show that niche
      diversification peaks at intermediate levels of resource availability. We suggest
      that this unimodal relationship is due to evolutionary diversification that is
      driven by competition for resources but constrained by the ecological opportunity
      represented by different resource types. These processes may underlie some
      general patterns of diversity, including latitudinal gradients in species
      richness and the effects of anthropogenic enrichment of the environment.

PMID- 17015336
TI  - Queen promiscuity lowers disease within honeybee colonies.
AB  - Most species of social insects have singly mated queens, but in some species each
      queen mates with numerous males to create a colony with a genetically diverse
      worker force. The adaptive significance of polyandry by social insect queens
      remains an evolutionary puzzle. Using the honeybee (Apis mellifera), we tested
      the hypothesis that polyandry improves a colony's resistance to disease. We
      established colonies headed by queens that had been artificially inseminated by
      either one or 10 drones. Later, we inoculated these colonies with spores of
      Paenibacillus larvae, the bacterium that causes a highly virulent disease of
      honeybee larvae (American foulbrood). We found that, on average, colonies headed
      by multiple-drone inseminated queens had markedly lower disease intensity and
      higher colony strength at the end of the summer relative to colonies headed by
      single-drone inseminated queens. These findings support the hypothesis that
      polyandry by social insect queens is an adaptation to counter disease within
      their colonies.

PMID- 17015337
TI  - Experimentally induced change in infectious period affects transmission dynamics
      in a social group.
AB  - A key component of any epidemiological model is the infectious period, which
      greatly affects the dynamics and persistence of an infection. Social
      organization, leading to behavioural and spatial heterogeneities among potential
      susceptibles, interacts with infectious period to create different risk
      categories within a group. Using the honeybee (Apis mellifera) colony as a social
      model, a protocol that creates different infectious periods in individual bees
      and another that follows the diffusion of a transmittable tracer within a colony,
      we show experimentally how a short infectious period results in an epidemic
      process with low prevalence confined only to individuals at the outer edge of a
      group, while a long infectious period results in high prevalence distributed more
      universally among all the group members. We call this finding an evidence of
      'organizational immunity' in a social network and propose that the honeybee
      colony provides a unique opportunity to test its role in social transmission
      processes.

PMID- 17015338
TI  - Are apes really inequity averse?
AB  - Brosnan et al. (Brosnan, S. F. Schiff, H. C. & de Waal, F. B. M. 2005 Tolerance
      for inequity may increase with social closeness in chimpanzees. Proc. R. Soc.
      B272, 253-258) found that chimpanzees showed increased levels of rejection for
      less-preferred food when competitors received better food than themselves and
      postulated as an explanation inequity aversion. In the present study, we extended
      these findings by adding important control conditions, and we investigated
      whether inequity aversion could also be found in the other great ape species and
      whether it would be influenced by subjects' relationship with the competitor. In
      the present study, subjects showed a pattern of food rejection opposite to the
      subjects of the above study by Brosnan et al. (2005). Our apes ignored fewer food
      pieces and stayed longer in front of the experimenter when a conspecific received
      better food than themselves. Moreover, chimpanzees begged more vigorously when
      the conspecific got favoured food. The most plausible explanation for these
      results is the food expectation hypothesis - seeing another individual receive
      high-quality food creates the expectation of receiving the same food oneself -
      and not inequity aversion.

PMID- 17015339
TI  - Negotiations within the family over the supply of parental care.
AB  - Adults provisioning dependent young are in conflict with their partners, who
      would prefer a greater level of effort, and with their offspring, who would
      prefer a greater supply of food. To what extent, then should adults negotiate
      their provisioning behaviour with other family members? We used experimental
      manipulations of brood size, and targeted playback of begging calls to determine
      the extent to which adult great tits Parus major adjust their provisioning rates
      in response to the behaviour of their partner and their brood. We found that
      males and females behaved similarly, both responding more to each other's
      behaviour than to chick calling. We also found that the degree to which adults
      negotiated their provisioning rates with each other varied between years. A
      review of the literature suggests that the extent of negotiation over
      provisioning is likely to vary not only between species of diverse taxa, but also
      between and within (this study) populations of the same species. We suggest that
      provisioning behaviour lies on a 'negotiation continuum', which describes the
      extent to which parents respond to the actions of other family members. We argue
      that an individual's location on the 'negotiation continuum' is determined partly
      by the extent to which it can physically respond to the behaviour shown by other
      members of the family and partly by the quality of information on offer.

PMID- 17015340
TI  - Negotiation of mutualism: rhizobia and legumes.
AB  - The evolution and persistence of biological cooperation have been an important
      puzzle in evolutionary theory. Here, we suggest a new approach based on
      bargaining theory to tackle the question. We present a mechanistic model for
      negotiation of benefits between a nitrogen-fixing nodule and a legume plant. To
      that end, we first derive growth rates for the nodule and plant from metabolic
      models of each as a function of material fluxes between them. We use these growth
      rates as pay-off functions in the negotiation process, which is analogous to
      collective bargaining between a firm and a workers' union. Our model predicts
      that negotiations lead to the Nash bargaining solution, maximizing the product of
      players' pay-offs. This work introduces elements of cooperative game theory into
      the field of mutualistic interactions. In the discussion of the paper, we argue
      for the benefits of such an approach in studying the question of biological
      cooperation.

PMID- 17015341
TI  - Sexual selection predicts advancement of avian spring migration in response to
      climate change.
AB  - Global warming has led to earlier spring arrival of migratory birds, but the
      extent of this advancement varies greatly among species, and it remains uncertain
      to what degree these changes are phenotypically plastic responses or
      microevolutionary adaptations to changing environmental conditions. We suggest
      that sexual selection could help to understand this variation, since early spring
      arrival of males is favoured by female choice. Climate change could weaken the
      strength of natural selection opposing sexual selection for early migration,
      which would predict greatest advancement in species with stronger female choice.
      We test this hypothesis comparatively by investigating the degree of long-term
      change in spring passage at two ringing stations in northern Europe in relation
      to a synthetic estimate of the strength of female choice, composed of degree of
      extra-pair paternity, relative testes size and degree of sexually dichromatic
      plumage colouration. We found that species with a stronger index of sexual
      selection have indeed advanced their date of spring passage to a greater extent.
      This relationship was stronger for the changes in the median passage date of the
      whole population than for changes in the timing of first-arriving individuals,
      suggesting that selection has not only acted on protandrous males. These results
      suggest that sexual selection may have an impact on the responses of organisms to
      climate change, and knowledge of a species' mating system might help to inform
      attempts at predicting these.

PMID- 17015343
TI  - Spontaneous gene flow from rapeseed (Brassica napus) to wild Brassica oleracea.
AB  - Research on the environmental risks of gene flow from genetically modified (GM)
      crops to wild relatives has traditionally emphasized recipients yielding most
      hybrids. For GM rapeseed (Brassica napus), interest has centred on the
      'frequently hybridizing' Brassica rapa over relatives such as Brassica oleracea,
      where spontaneous hybrids are unreported in the wild. In two sites, where
      rapeseed and wild B. oleracea grow together, we used flow cytometry and crop
      specific microsatellite markers to identify one triploid F1 hybrid, together with
      nine diploid and two near triploid introgressants. Given the newly discovered
      capacity for spontaneous introgression into B. oleracea, we then surveyed
      associated flora and fauna to evaluate the capacity of both recipients to harm
      cohabitant species with acknowledged conservational importance. Only B. oleracea
      occupies rich communities containing species afforded legislative protection;
      these include one rare micromoth species that feeds on B. oleracea and warrants
      further assessment. We conclude that increased attention should now focus on B.
      oleracea and similar species that yield few crop-hybrids, but possess scope to
      affect rare or endangered associates.

PMID- 17015342
TI  - Anti-parasite treatment removes negative effects of environmental pollutants on
      reproduction in an Arctic seabird.
AB  - Recent studies have shown that the detrimental effects of anthropogenic
      pollutants may be worse if organisms are exposed to natural stress. In this
      study, we examined whether negative effects of organochlorines (OCs) could be
      influenced by parasites. In two breeding seasons, we administered an anti
      helminthic drug to groups of breeding glaucous gulls (Larus hyperboreus), whereas
      control groups were placebo treated. In all birds, blood residues of the most
      important OCs in the study population (hexachlorobenzene, oxychlordane, p,p'
      dichlorodiphenyldichloroethylene and polychlorinated biphenyl), were measured.
      The relationships between OCs and fitness components (i.e. nesting success and
      return rate between breeding seasons) were then compared between the birds
      receiving anti-parasite treatment and the controls. Among untreated males, higher
      blood residues of OCs were associated with lowered nesting success, while in
      males receiving anti-parasite treatment, there was no detrimental effect of OCs
      on fitness. Return rate was not affected by treatment or OCs. Our findings
      suggest that parasites may be an important factor in triggering reproductive
      effects of such pollutants, and that relatively low levels of OCs may have
      serious reproductive consequences in natural populations when stress from other
      sources is high.

PMID- 17015344
TI  - Genetic models of homosexuality: generating testable predictions.
AB  - Homosexuality is a common occurrence in humans and other species, yet its genetic
      and evolutionary basis is poorly understood. Here, we formulate and study a
      series of simple mathematical models for the purpose of predicting empirical
      patterns that can be used to determine the form of selection that leads to
      polymorphism of genes influencing homosexuality. Specifically, we develop theory
      to make contrasting predictions about the genetic characteristics of genes
      influencing homosexuality including: (i) chromosomal location, (ii) dominance
      among segregating alleles and (iii) effect sizes that distinguish between the two
      major models for their polymorphism: the overdominance and sexual antagonism
      models. We conclude that the measurement of the genetic characteristics of
      quantitative trait loci (QTLs) found in genomic screens for genes influencing
      homosexuality can be highly informative in resolving the form of natural
      selection maintaining their polymorphism.

PMID- 17015345
TI  - Testing hypotheses of Pleistocene population history using coalescent
      simulations: phylogeography of the pygmy nuthatch (Sitta pygmaea).
AB  - In this paper, we use mitochondrial NADH dehydrogenase subunit 2 sequences to
      test Pleistocene refugial hypotheses for the pygmy nuthatch (Sitta pygmaea).
      Pygmy nuthatches are a common resident of long-needle pine forests in western
      North America and demonstrate a particular affinity with ponderosa pine (Pinus
      ponderosa). Palaeoecological and genetic data indicate that ponderosa pine was
      isolated in two Pleistocene refugia corresponding to areas in the southern Sierra
      Nevada in the west and southern Arizona and New Mexico in the east. We use
      coalescent simulations to test the hypothesis that pygmy nuthatches tracked the
      Pleistocene history of their preferred habitat and persisted in two refugia
      during the periods of glacial maxima. Coalescent simulation of population history
      does not support the hypothesis of two Pleistocene refugia for the pygmy
      nuthatch. Instead, our data are consistent with a single refuge model. Nucleotide
      diversity is greatest in the western populations of southern and coastal
      California. We suggest that the pygmy nuthatch expanded from a far western
      glacial refuge into its current distribution since the most recent glacial
      maximum.

PMID- 17015346
TI  - Altered host behaviour and brain serotonergic activity caused by
      acanthocephalans: evidence for specificity.
AB  - Manipulative parasites can alter the phenotype of intermediate hosts in various
      ways. However, it is unclear whether such changes are just by-products of
      infection or adaptive and enhance transmission to the final host. Here, we show
      that the alteration of serotonergic activity is functionally linked to the
      alteration of specific behaviour in the amphipod Gammarus pulex infected with
      acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent,
      Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G.
      pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5
      hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered
      phototactism, but had no effect on geotactism. Photophilic G. pulex infected with
      P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity
      compared to photophobic, uninfected individuals. In contrast, brain 5-HT
      immunoreactivity did not differ between P. minutus-infected and uninfected G.
      pulex. Finally, brain 5-HT immunoreactivity differed significantly among P.
      tereticollis-infected individuals in accordance with their degree of
      manipulation. Our results demonstrate that altered 5-HT activity is not the mere
      consequence of infection by acanthocephalans but is specifically linked to the
      disruption of host photophobic behaviour, whereas the alteration of other
      behaviours such as geotactism may rely on distinct physiological routes.

PMID- 17015347
TI  - How do pathogen evolution and host heterogeneity interact in disease emergence?
AB  - Heterogeneity in the parameters governing the spread of infectious diseases is a
      common feature of real-world epidemics. It has been suggested that for pathogens
      with basic reproductive number R(0)>1, increasing heterogeneity makes extinction
      of disease more likely during the early rounds of transmission. The basic
      reproductive number R(0) of the introduced pathogen may, however, be less than 1
      after the introduction, and evolutionary changes are then required for R(0) to
      increase to above 1 and the pathogen to emerge. In this paper, we consider how
      host heterogeneity influences the emergence of both non-evolving pathogens and
      those that must undergo adaptive changes to spread in the host population. In
      contrast to previous results, we find that heterogeneity does not always make
      extinction more likely and that if adaptation is required for emergence, the
      effect of host heterogeneity is relatively small. We discuss the application of
      these ideas to vaccination strategies.

PMID- 17015348
TI  - Attraction independent of detection suggests special mechanisms for symmetry
      preferences in human face perception.
AB  - Symmetrical human faces are attractive and it has been proposed that humans have
      a specialized mechanism for detecting symmetry in faces and that sensitivity to
      symmetry determines symmetry preferences. Here, we show that symmetry preferences
      are influenced by inversion, whereas symmetry detection is not and that within
      individuals the ability to detect facial symmetry is not related to preferences
      for facial symmetry. Taken together, these findings suggest that symmetry
      preferences are indeed driven by a mechanism that is independent of conscious
      detection. A specialized mechanism for symmetry preference independent of
      detection may be the result of specific pressures faced by human ancestors to
      select high-quality mates and could support a modular view of mate choice.
      Unconscious mechanisms determining face preferences may explain why the reasons
      behind attraction are often difficult to articulate and demonstrate that
      detection alone cannot explain symmetry preferences.

PMID- 17015349
TI  - Impact of mating systems on patterns of sequence polymorphism in flowering
      plants.
AB  - A fundamental challenge in population genetics and molecular evolution is to
      understand the forces shaping the patterns of genetic diversity within and among
      species. Among them, mating systems are thought to have important influences on
      molecular diversity and genome evolution. Selfing is expected to reduce effective
      population size, Ne, and effective recombination rates, directly leading to
      reduced polymorphism and increased linkage disequilibrium compared with
      outcrossing. Increased isolation between populations also results directly from
      selfing or indirectly from evolutionary changes, such as small flowers and low
      pollen output, leading to greater differentiation of molecular markers than under
      outcrossing. The lower effective recombination rate increases the likelihood of
      hitch-hiking, further reducing within-deme diversity of selfers and thus
      increasing their genetic differentiation. There are also indirect effects on
      molecular evolutionary processes. Low Ne reduces the efficacy of selection; in
      selfers, selection should thus be less efficient in removing deleterious
      mutations. The rarity of heterozygous sites in selfers leads to infrequent action
      of biased conversion towards GC, which tends to increase sequences' GC content in
      the most highly recombining genome regions of outcrossers. To test these
      predictions in plants, we used a newly developed sequence polymorphism database
      to investigate the effects of mating system differences on sequence polymorphism
      and genome evolution in a wide set of plant species. We also took into account
      other life-history traits, including life form (whether annual or perennial
      herbs, and woody perennial) and the modes of pollination and seed dispersal,
      which are known to affect enzyme and DNA marker polymorphism. We show that among
      various life-history traits, mating systems have the greatest influence on
      patterns of polymorphism.

PMID- 17015350
TI  - Life history and environmental variation interact to determine effective
      population to census size ratio.
AB  - Successful recovery and sustainability of threatened and exploited species
      depends in part on retention and maintenance of genetic diversity. Theory
      indicates that genetic diversity is lost at a rate inversely proportional to the
      genetically effective population size (N(e)), which is roughly equal to one-half
      the adult census size (N) in many organisms. However, N(e) has been reported to
      be up to five orders of magnitude lower than N in species with life histories
      that result in type III survivorship (high fecundity, but heavy mortality in
      early life stages, e.g. bony fishes), prompting speculation that low values of
      N(e) may be a general feature of such organisms despite sometimes vast
      abundances. Here, we compared N(e) and the ratio N(e)/N across three ecologically
      similar fish species from the arid southwestern United States, all with type III
      life histories but with differing expectations of egg and larval survivorship
      that correlate with the degree of human-imposed habitat fragmentation. Our study
      indicates that type III life history may be necessary, but this alone is
      insufficient to account for extraordinarily low values of N(e)/N. Rather, life
      history interacts with environmentally imposed mortality to determine the rate
      and magnitude of change in genetic diversity in these desert fish species.

PMID- 17015351
TI  - New insights into neuropeptide modulation of aggression: field studies of
      arginine vasotocin in a territorial tropical damselfish.
AB  - The neuropeptides arginine vasotocin (AVT) and arginine vasopressin are key
      modulators of affiliation and aggression among non-mammalian and mammalian
      vertebrates, respectively. Here, we explored AVT's effect on aggression in a wild
      population of beaugregory damselfish, Stegastes leucostictus, a highly
      territorial species. Aggression by territorial males towards 'intruders' (bottled
      fishes) was assessed before and after each male received intramuscular injections
      of either AVT, Manning compound (an AVT V1a receptor antagonist), isotocin (the
      teleost homologue of mammalian oxytocin differing from AVT by two amino acids) or
      saline (vehicle control). Compared to saline controls, AVT and Manning increased
      and decreased aggression, respectively, while isotocin had no effect. Response
      selectivity was further established in a dose-response study that revealed an
      inverted U-shaped function. Compared to saline controls, aggression levels for
      low and high AVT doses were similar, while medium dose treatments were
      significantly greater. This type of behavioural response, the first that we know
      of for a vertebrate neuropeptide, could depend on the binding of AVT to both V1
      type and other AVT or non-AVT receptors. The pattern revealed here for damselfish
      may be symptomatic of species- and context-dependent specificity of AVT's
      modulation of aggression across teleosts, as is currently proposed for tetrapods.

PMID- 17015352
TI  - Phylogenomics of the genus Mus (Rodentia; Muridae): extensive genome repatterning
      is not restricted to the house mouse.
AB  - The house mouse (Mus musculus) is universally adopted as the mammalian laboratory
      model, and it is involved in most studies of large-scale comparative genomics.
      Paradoxically, this taxon is rarely the index species for evolutionary analyses
      of genome architecture owing to its highly rearranged karyotype. To unravel the
      origin and nature of this extensive repatterning genome, we performed a
      multidirectional chromosome painting study of representative species within the
      genus Mus. However, the latter includes four extant subgenera (Mus, Coelomys,
      Nannomys and Pyromys) between which the phylogenetic relationships remain elusive
      despite the numerous molecular studies. Comparative genomic maps were established
      using chromosome-specific painting probes of the laboratory mouse and Nannomys
      minutoides. Hence, by integrating closely related species within Mus, this study
      allowed us to: (i) unambiguously resolve for the first time the long-standing
      controversial phylogeny, (ii) trace the evolution of genome organization in the
      house mouse, (iii) track rearrangements that necessitated new centromere
      locations, i.e. formation of neocentromere or reactivation of latent centromeres,
      (iv) reveal an extremely high rate of karyotypic evolution, with a 10- to 30-fold
      acceleration which was coincidental with subgeneric cladogenesis and (v)
      highlight genomic areas of interest for high-resolution studies on neocentromere
      formation and synteny breakpoints.

PMID- 17015353
TI  - Escalated conflict in a social hierarchy.
AB  - Animals that live in cooperative societies form hierarchies in which dominant
      individuals reap disproportionate benefits from group cooperation. The stability
      of these societies requires subordinates to accept their inferior status rather
      than engage in escalated conflict with dominants over rank. Applying the logic of
      animal contests to these cases predicts that escalated conflict is more likely
      where subordinates are reproductively suppressed, where group productivity is
      high, relatedness is low, and where subordinates are relatively strong. We tested
      these four predictions in the field on co-foundress associations of the paper
      wasp Polistes dominulus by inducing contests over dominance rank experimentally.
      Subordinates with lower levels of ovarian development, and those in larger, more
      productive groups, were more likely to escalate in conflict with their dominant,
      as predicted. Neither genetic relatedness nor relative body size had significant
      effects on the probability of escalation. The original dominant emerged as the
      winner in all except one escalated contest. The results provide the first
      evidence that reproductive suppression of subordinates increases the threat of
      escalated conflict, and hence that reproductive sharing can promote stability of
      the dominant-subordinate relationship.

PMID- 17015354
TI  - Periodical cicadas use light for oviposition site selection.
AB  - Organisms use incomplete information from local experience to assess the
      suitability of potential habitat sites over a wide range of spatial and temporal
      scales. Although ecologists have long recognized the importance of spatial scales
      in habitat selection, few studies have investigated the temporal scales of
      habitat selection. In particular, cues in the immediate environment may commonly
      provide indirect information about future habitat quality. In periodical cicadas
      (Magicicada spp.), oviposition site selection represents a very long-term habitat
      choice. Adult female cicadas insert eggs into tree branches during a few weeks in
      the summer of emergence, but their oviposition choices determine the underground
      habitats of root-feeding nymphs over the following 13 or 17 years. Here, field
      experiments are used to show that female cicadas use the local light environment
      of host trees during the summer of emergence to select long-term host trees.
      Light environments may also influence oviposition microsite selection within
      hosts, suggesting a potential behavioural mechanism for associating solar cues
      with host trees. In contrast, experimental nutrient enrichment of host trees did
      not influence cicada oviposition densities. These findings suggest that the light
      environments around host trees may provide a robust predictor of host tree
      quality in the near future. This habitat selection may influence the spatial
      distribution of several cicada-mediated ecological processes in eastern North
      American forests.

PMID- 17015355
TI  - Outcome expectations drive learned behaviour in larval Drosophila.
AB  - Why does Pavlov's dog salivate? In response to the tone, or in expectation of
      food? While in vertebrates behaviour can be driven by expected outcomes, it is
      unknown whether this is true for non-vertebrates as well. We find that, in the
      Drosophila larva, odour memories are expressed behaviourally only if animals can
      expect a positive outcome from doing so. The expected outcome of tracking down an
      odour is determined by comparing the value of the current situation with the
      value of the memory for that odour. Memory is expressed behaviourally only if the
      expected outcome is positive. This uncovers a hitherto unrecognized evaluative
      processing step between an activated memory trace and behaviour control, and
      argues that learned behaviour reflects the pursuit of its expected outcome. Shown
      in a system with a simple brain, an apparently cognitive process like
      representing the expected outcome of behaviour seems to be a basic feature of
      behaviour control.

PMID- 17015356
TI  - An experimental test of the contributions and condition dependence of
      microstructure and carotenoids in yellow plumage coloration.
AB  - A combination of structural and pigmentary components is responsible for many of
      the colour displays of animals. Despite the ubiquity of this type of coloration,
      neither the relative contribution of structures and pigments to variation in such
      colour displays nor the relative effects of extrinsic factors on the structural
      and pigment-based components of such colour has been determined. Understanding
      the sources of colour variation is important because structures and pigments may
      convey different information to conspecifics. In an experiment on captive
      American goldfinches Carduelis tristis, we manipulated two parameters, carotenoid
      availability and food availability, known to affect the expression of carotenoid
      pigments in a full-factorial design. Yellow feathers from these birds were then
      analysed in two ways. First, we used full-spectrum spectrometry and high
      performance liquid chromatography to examine the extent to which variation in
      white structural colour and total carotenoid content was associated with
      variation in colour properties of feathers. The carotenoid content of yellow
      feathers predicted two colour parameters (principal component 1--representing
      high values of ultraviolet and yellow chroma and low values of violet-blue chroma
      and hue). Two different colour parameters (violet-blue and yellow chroma) from
      white de-pigmented feathers, as well as carotenoid content, predicted reflectance
      measurements from yellow feathers. Second, we determined the relative effects of
      our experimental manipulations on white structural colour and yellow colour.
      Carotenoid availability directly affected yellow colour, while food availability
      affected it only in combination with carotenoid availability. None of our
      manipulations had significant effects on the expression of white structural
      colour. Our results suggest that the contribution of microstructures to variation
      in the expression of yellow coloration is less than the contribution of
      carotenoid content, and that carotenoid deposition is more dependent on extrinsic
      variability than is the production of white structural colour.

PMID- 17015357
TI  - Ecological correlates of population genetic structure: a comparative approach
      using a vertebrate metacommunity.
AB  - Identifying ecological factors associated with population genetic differentiation
      is important for understanding microevolutionary processes and guiding the
      management of threatened populations. We identified ecological correlates of
      several population genetic parameters for three interacting species (two garter
      snakes and an anuran) that occupy a common landscape. Using multiple regression
      analysis, we found that species interactions were more important in explaining
      variation in population genetic parameters than habitat and nearest-neighbour
      characteristics. Effective population size was best explained by census size,
      while migration was associated with differences in species abundance. In
      contrast, genetic distance was poorly explained by the ecological correlates that
      we tested, but geographical distance was prominent in models for all species. We
      found substantially different population dynamics for the prey species relative
      to the two predators, characterized by larger effective sizes, lower gene flow
      and a state of migration-drift equilibrium. We also identified an escarpment
      formed by a series of block faults that serves as a barrier to dispersal for the
      predators. Our results suggest that successful landscape-level management should
      incorporate genetic and ecological data for all relevant species, because even
      closely associated species can exhibit very different population genetic dynamics
      on the same landscape.

PMID- 17015358
TI  - A social basis for the development of primary males in a sex-changing fish.
AB  - An example of alternative male strategies is seen in diandric protogynous (female
      first) hermaphrodites, where individuals either mature directly as male (primary
      males) or first reproduce as female and then change sex to male (secondary
      males). In some sex-changing fishes, the testes of primary males appear
      anatomically similar to those of non-sex-changing species, whereas the testes of
      secondary males have anatomical evidence of their former ovarian function. Here,
      we provide evidence that in the bluehead wrasse, Thalassoma bifasciatum, these
      strikingly different male phenotypes arise from differences in the ontogenetic
      timing of environmental sex determination, timing that can be experimentally
      altered through changes in the social circumstances. Juveniles differentiated
      almost exclusively as females when reared in isolation, regardless of whether
      they were collected from a reef with a high proportion of primary males or from a
      reef with a low proportion of primary males. In contrast, one individual usually
      differentiated as a primary male when reared in groups of three. Our results
      indicate that primary males of the bluehead wrasse are an environmentally
      sensitive developmental strategy that has probably evolved in response to
      variation in the reproductive success of primary males in populations of
      different sizes.

PMID- 17015359
TI  - Modelling population persistence on islands: mammal introductions in the New
      Zealand archipelago.
AB  - Islands are likely to differ in their susceptibility to colonization or invasion
      due to variation in factors that affect population persistence, including island
      area, climatic severity and habitat modification. We tested the importance of
      these factors in explaining the persistence of 164 introductions of six mammal
      species to 85 islands in the New Zealand archipelago using survival analysis and
      model selection techniques. As predicted by the theory of stochastic population
      growth, extinction risk was the greatest in the period immediately following
      introduction, declining rapidly to low probability by ca 25 years. This suggests
      that initially small populations were at greatest risk of extinction and that
      populations which survived for 25 years were likely to persist subsequently for
      much longer. Islands in the New Zealand archipelago become colder and windier
      with increasing latitude, and the probability of mammal populations persisting on
      islands declined steeply with increasing latitude. Hence, our results suggest
      that climatic suitability was an important determinant of the outcome of these
      invasions. The form of the relationship between latitude and persistence
      probability differed among species, emphasizing that the outcome of colonization
      attempts is species-environment specific.

PMID- 17015360
TI  - Global phylogeographic limits of Hawaii's avian malaria.
AB  - The introduction of avian malaria (Plasmodium relictum) to Hawaii has provided a
      model system for studying the influence of exotic disease on naive host
      populations. Little is known, however, about the origin or the genetic variation
      of Hawaii's malaria and traditional classification methods have confounded
      attempts to place the parasite within a global ecological and evolutionary
      context. Using fragments of the parasite mitochondrial gene cytochrome b and the
      nuclear gene dihydrofolate reductase-thymidylate synthase obtained from a global
      survey of greater than 13000 avian samples, we show that Hawaii's avian malaria,
      which can cause high mortality and is a major limiting factor for many species of
      native passerines, represents just one of the numerous lineages composing the
      morphological parasite species. The single parasite lineage detected in Hawaii
      exhibits a broad host distribution worldwide and is dominant on several other
      remote oceanic islands, including Bermuda and Moorea, French Polynesia. The
      rarity of this lineage in the continental New World and the restriction of
      closely related lineages to the Old World suggest limitations to the transmission
      of reproductively isolated parasite groups within the morphological species.

PMID- 17015361
TI  - The evolutionary emergence of pandemic influenza.
AB  - Pandemic influenza remains a serious public health threat and the processes
      involved in the evolutionary emergence of pandemic influenza strains remain
      incompletely understood. Here, we develop a stochastic model for the evolutionary
      emergence of pandemic influenza, and use it to address three main questions. (i)
      What is the minimum annual number of avian influenza virus infections required in
      humans to explain the historical rate of pandemic emergence? (ii) Are such avian
      influenza infections in humans more likely to give rise to pandemic strains if
      they are driven by repeated cross-species introductions, or by low-level
      transmission of avian influenza viruses between humans? (iii) What are the most
      effective interventions for reducing the probability that an influenza strain
      with pandemic potential will evolve? Our results suggest that if evolutionary
      emergence of past pandemics has occurred primarily through viral reassortment in
      humans, then thousands of avian influenza virus infections in humans must have
      occurred each year for the past 250 years. Analyses also show that if there is
      epidemiologically significant variation among avian influenza virus genotypes,
      then avian virus outbreaks stemming from repeated cross-species transmission
      events result in a greater likelihood of a pandemic strain evolving than those
      caused by low-level transmission between humans. Finally, public health
      interventions aimed at reducing the duration of avian virus infections in humans
      give the greatest reduction in the probability that a pandemic strain will
      evolve.

PMID- 17015362
TI  - Pathogens, density dependence and the coexistence of tropical trees.
AB  - There is increasing interest in the role played by density-dependent mortality
      from natural enemies, particularly plant pathogens, in promoting the coexistence
      and diversity of tropical trees. Here, we review four issues in the analysis of
      pathogen-induced density dependence that have been overlooked or inadequately
      addressed. First, the methodology for detecting density dependence must be robust
      to potential biases. Observational studies, in particular, require a careful
      analysis to avoid biases generated by measurement error, and existing studies
      could be criticized on these grounds. Experimental studies manipulating plant
      density and pathogen incidence will often be preferable, or should be run in
      parallel. Second, the form of density dependence is not well understood and, in
      particular, there are no data indicating whether pathogens cause compensating or
      overcompensating density responses. Owing to this, we argue that the potential
      for pathogen-induced density dependence to generate diversity-enhancing outcomes,
      such as the Janzen-Connell effect, remains uncertain, as coexistence is far more
      probable if density dependence is overcompensating. Third, there have been few
      studies examining the relative importance of intra- or interspecific density
      dependence resulting from pathogens (or, more widely, natural enemies). This is
      essentially equivalent to asking to what extent pathogens are host-specific. If
      pathogens are generalists, then mortality rates will respond to overall plant
      density, irrespective of plant species identity. This will weaken the
      intraspecific density dependence and reduce the diversity-promoting effects of
      pathogens. Finally, we highlight the need for studies that integrate observations
      and experiments on pathogens and density dependence into the whole life cycle of
      trees, because as yet it is not possible to be certain of the degree to which
      pathogens contribute to observed dynamics.

PMID- 17015363
TI  - The ideal free pike: 50 years of fitness-maximizing dispersal in Windermere.
AB  - The ideal free distribution (IFD) theory is one of the most influential theories
      in evolutionary ecology. It predicts how animals ought to distribute themselves
      within a heterogeneous habitat in order to maximize lifetime fitness. We test the
      population level consequence of the IFD theory using 40-year worth data on pike
      (Esox lucius) living in a natural lake divided into two basins. We do so by
      employing empirically derived density-dependent survival, dispersal and fecundity
      functions in the estimation of basin-specific density-dependent fitness surfaces.
      The intersection of the fitness surfaces for the two basins is used for deriving
      expected spatial distributions of pike. Comparing the derived expected spatial
      distributions with 50 years data of the actual spatial distribution demonstrated
      that pike is ideal free distributed within the lake. In general, there was a net
      migration from the less productive north basin to the more productive south
      basin. However, a pike density-manipulation experiment imposing shifting pike
      density gradients between the two basins managed to switch the net migration
      direction and hence clearly demonstrated that the Windermere pike choose their
      habitat in an ideal free manner. Demonstration of ideal free habitat selection on
      an operational field scale like this has never been undertaken before.

PMID- 17015364
TI  - Dark nests and egg colour in birds: a possible functional role of ultraviolet
      reflectance in egg detectability.
AB  - Owing to the conspicuousness of ultraviolet (UV) colour in dark environments,
      natural selection might have selected UV egg coloration because it would enhance
      egg detectability by parents in murky nests. Here, we tested this hypothesis by
      using comparative and experimental approaches. First, we studied variation in egg
      coloration of 98 species of European passerines measured using UV-visible
      reflectance spectrometry (300-700nm) in relation to nesting habits. Analyses
      based on raw data and controlling for phylogenetic distances both at the species
      and the family levels revealed that hole-nester species produced eggs with higher
      UV reflectance than those nesting in open habitats. The experimental approach
      consisted of the manipulation of UV reflectance of the experimental eggs
      introduced outside the nest-cup of the hole-nester spotless starling Sturnus
      unicolor and the study of the retrieval of these eggs. Ultraviolet-reflecting
      eggs (controls) were more frequently retrieved to the nest-cup than non
      reflecting (-UV) eggs. These results were not due to '-UV' eggs being recognized
      by starlings as parasitic because when a parasitic egg is detected, starlings
      removed it from the nest-box. Therefore, these results are consistent with the
      hypothesis that UV egg colours are designed to provide highly detectable targets
      for parent birds in dark nest environments.

PMID- 17015365
TI  - Covariance of phenotypically plastic traits induces an adaptive shift in host
      selection behaviour.
AB  - Flexibility in adult body size allows generalist parasitoids to use many host
      species at a cost of producing a range of adult sizes. Consequently, host
      selection behaviour must also maintain a level of flexibility as adult size is
      related to capture efficiency. In the present study, we investigated covariance
      of two plastic traits--size at pupation and host size selection behaviour-using
      Aphidius ervi reared on either Acyrthosiphon pisum or Aulacorthum solani,
      generating females of disparate sizes. Natal host was shown to change the ranking
      of perceived host quality with relation to host size. Parasitoids preferentially
      attacked hosts that corresponded to the size of the second instar of their natal
      host species. This resulted in optimal host selection behaviour when parasitoids
      were exposed to the same host species from which they emerged. Parasitoid size
      was positively correlated with host size preference, indicating that females use
      relative measurements when selecting suitable hosts. These coadapted gene
      complexes allow generalist parasitoids to effectively use multiple host species
      over several generations. However, the fixed nature of the behavioural response,
      within a parasitoid's lifetime, suggests that these traits may have evolved in a
      patchy host species environment.

PMID- 17015366
TI  - Serotype cycles in cholera dynamics.
AB  - Interest in understanding strain diversity and its impact on disease dynamics has
      grown over the past decade. Theoretical disease models of several co-circulating
      strains indicate that incomplete cross-immunity generates conditions for strain
      cycling behaviour at the population level. However, there have been no
      quantitative analyses of disease time-series that are clear examples of
      theoretically expected strain cycling. Here, we analyse a 40-year (1966-2005)
      cholera time-series from Bangladesh to determine whether patterns evident in
      these data are compatible with serotype-cycling behaviour. A mathematical two
      serotype model is capable of explaining the oscillations in case patterns when
      cross-immunity between the two serotypes, Inaba and Ogawa, is high. Further
      support that cholera's serotype-cycling arises from population-level immunity
      patterns is provided by calculations of time-varying effective reproductive
      rates. These results shed light on historically observed serotype dominance
      shifts and have important implications for cholera early warning systems.

PMID- 17015367
TI  - Climate change and the demographic demise of a hoarding bird living on the edge.
AB  - Population declines along the lower-latitude edge of a species' range may be
      diagnostic of climate change. We report evidence that climate change has
      contributed to deteriorating reproductive success in a rapidly declining
      population of the grey jay (Perisoreus canadensis) at the southern edge of its
      range. This non-migratory bird of boreal and subalpine forest lives on permanent
      territories, where it hoards enormous amounts of food for winter and then breeds
      very early, under still-wintry conditions. We hypothesized that warmer autumns
      have increased the perishability of hoards and compromised subsequent breeding
      attempts. Our analysis confirmed that warm autumns, especially when followed by
      cold late winters, have led to delayed breeding and reduced reproductive success.
      Our findings uniquely show that weather months before the breeding season impact
      the timing and success of breeding. Warm autumns apparently represent hostile
      conditions for this species, because it relies on cold storage. Our study
      population may be especially vulnerable, because it is situated at the southern
      edge of the range, where the potential for hoard rot is most pronounced. This
      population's demise may signal a climate-driven range contraction through local
      extinctions along the trailing edge.

PMID- 17015368
TI  - Temporal habitat variability and the maintenance of sex in host populations of
      the pea aphid.
AB  - The evolutionary maintenance of sex, despite competition from asexual
      reproduction, has long intrigued the evolutionary biologists owing to its
      numerous apparent short-term costs. In aphids, winter climate is expected to
      determine the maintenance of sexual lineages in the high latitude zones owing to
      their exclusive ability to produce frost-resistant eggs. However, diverse
      reproductive modes may coexist at a local scale where climatic influence is
      counteracted by microgeographical factors. In this study, we tested the influence
      of local habitat characteristics on regional coexistence of reproductive modes in
      the pea aphid, Acyrthosiphon pisum. In the laboratory, the induction of sexual
      morph production of many pea aphid genotypes from the local fields of annual (pea
      and faba bean) and perennial (alfalfa and red clover) crops in Western France
      indicated that A. pisum lineages from annual crops had a significantly higher
      investment in sexual reproduction than A. pisum lineages from the perennial
      hosts. We propose that temporal habitat variability exerts a selective pressure
      to maintain the sexual reproduction in A. pisum. The ecological and evolutionary
      consequences of the association between the mode of reproduction and the host
      population on gene flow restriction and on ecological specialization are
      discussed.

PMID- 17015369
TI  - Controls on the distribution of productivity and organic resources in Antarctic
      Dry Valley soils.
AB  - The Antarctic Dry Valleys are regarded as one of the harshest terrestrial
      habitats on Earth because of the extremely cold and dry conditions. Despite the
      extreme environment and scarcity of conspicuous primary producers, the soils
      contain organic carbon and heterotrophic micro-organisms and invertebrates.
      Potential sources of organic compounds to sustain soil organisms include in situ
      primary production by micro-organisms and mosses, spatial subsidies from
      lacustrine and marine-derived detritus, and temporal subsidies ('legacies') from
      ancient lake deposits. The contributions from these sources at different sites
      are likely to be influenced by local environmental conditions, especially soil
      moisture content, position in the landscape in relation to lake level
      oscillations and legacies from previous geomorphic processes. Here we review the
      abiotic factors that influence biological activity in Dry Valley soils and
      present a conceptual model that summarizes mechanisms leading to organic
      resources therein.

PMID- 17015370
TI  - Revised evidence for facultative sex ratio adjustment in birds: a correction.
AB  - We provide a revision to the calculation of effect sizes and heterogeneity
      statistics in our original article, 'Facultative primary sex ratio variation: a
      lack of evidence in birds' (Ewen et al. 2004). Our revision shows that
      significant heterogeneity in sex ratio study effect sizes does indeed exist and
      that for a series of key traits the average effect sizes (while still weak) are
      in fact significantly different from zero.

PMID- 17015371
TI  - Effects of molecular rotation in low-energy electron collisions of H3+.
AB  - Measurements on the energetic structure of the dissociative recombination rate
      coefficient in the millielectronvolt range are described for H3+ ions produced in
      the lowest rotational levels by collisional cooling and stored as a fast beam in
      the magnetic storage ring TSR (Test Storage Ring). The observed resonant
      structure is consistent with that found previously at the storage ring facility
      CRYRING in Stockholm, Sweden; theoretical predictions yield good agreement on the
      overall size of the rate coefficient, but do not reproduce the detailed
      structure. First studies on the nuclear spin symmetry influencing the lowest
      level populations show a small effect different from the theoretical predictions.
      Heating processes in the residual gas and by collisions with energetic electrons,
      as well as cooling owing to interaction with cold electrons, were observed in
      long-time storage experiments, using the low-energy dissociative recombination
      rate coefficient as a probe, and their consistency with the recent cold H3+
      measurements is discussed.

PMID- 17015372
TI  - H3+: the driver of giant planet atmospheres.
AB  - We present a review of recent developments in the use of H3+ molecular ion as a
      probe of physics and chemistry of the upper atmospheres of giant planets. This
      ion is shown to be a good tracer of energy inputs into Jupiter (J), Saturn (S)
      and Uranus (U). It also acts as a 'thermostat', offsetting increases in the
      energy inputs owing to particle precipitation via cooling to space (J and U).
      Computer models have established that H3+ is also the main contributor to
      ionospheric conductivity. The coupling of electric and magnetic fields in the
      auroral polar regions leads to ion winds, which, in turn, drive neutral
      circulation systems (J and S). These latter two effects, dependent on H3+, also
      result in very large heating terms, approximately 5 x 10(12) W for Saturn and
      greater than 10(14) W for Jupiter, planet-wide; these terms compare with
      approximately 2.5 x 10(11) W of solar extreme UV absorbed at Saturn and 10(12) W
      at Jupiter. Thus, H3+ is shown to play a major role in explaining why the
      temperatures of the giant planets are much greater (by hundreds of kelvin) at the
      top of the atmosphere than solar inputs alone can account for.

PMID- 17015373
TI  - Explicitly correlated potential energy surface of H3+, including relativistic and
      adiabatic corrections.
AB  - After a short historical account of the theory of the H3+ ion, two ab initio
      methods are reviewed that allow the computation of the ground-state potential
      energy surface (PES) of H3+ in the Born-Oppenheimer (BO) approximation, with
      microhartree or even sub-microhartree accuracy, namely the R12 method and the
      method of explicitly correlated Gaussians. The BO-PES is improved by the
      inclusion of relativistic effects and adiabatic corrections. It is discussed how
      non-adiabatic effects on rotation and vibration can be simulated by corrections
      to the moving nuclear masses. The importance of the appropriate analytic fit to
      the computed points of the PES for the subsequent computation of the rovibronic
      spectrum is addressed. Some recent extensions of the computed PES in the energy
      region above the barrier to linearity are reviewed. This involves a large set of
      input geometries and the correct treatment of the dissociation asymptotics,
      including the coupling with the first excited singlet state. Some comments on
      this state as well as on the lowest triplet state of H3+ are made. The paper ends
      with a few remarks on the ion H5+.

PMID- 17015374
TI  - Submillimetre-wave lines of H2D+ and D2H+ as probes into chemistry in cold dark
      clouds.
AB  - We discuss past and recent progress of our continuing project of submillimetre
      wave spectroscopic investigations of H2D+ and D2H+. Three new lines of H2D+ in
      the 2.5-3.5 THz range are measured with a tunable far-infrared laser system.
      Since these molecules are very light asymmetric molecules, analysis based on a
      conventional effective Hamiltonian is not very useful in predicting the
      transition frequencies to the accuracy of the order of several MHz or better. In
      this respect, any addition of new accurate measurements of transition frequencies
      is important. In this paper, some discussions will be made on H5+ and its
      deuterated species as probable interstellar species in cold dark clouds. In
      particular, D3+, which is predicted to be abundant in cold dark clouds, can be
      (indirectly) detected by observing D3+ x H2.

PMID- 17015375
TI  - H3+ in the diffuse interstellar medium.
AB  - Three forms of solely hydrogen-bearing molecules--H2, HD and H3+--are observed in
      diffuse or optically transparent interstellar clouds. Although no comprehensive
      theory exists for the diffuse interstellar medium or its chemistry, the
      abundances of these species can generally be accommodated locally within the
      existing static equilibrium frameworks for heating/cooling, H2-formation on large
      grains, etc. with one modification demanded equally by observations of HD and
      H3+, i.e. a pervasive low-level source of H and H2 ionization ca 10 times faster
      than the usual cosmic ray ionization rate zetaH = 10(-17) s(-1) per free H-atom.
      We discuss this situation with reference to observation and time-dependent
      modelling of H2 and H3+ formation. While not wishing to appear ungrateful for the
      success of what are very simplistic notions of the interstellar medium, we point
      out several reasons not to feel smug. The equilibrium conditions which foster
      high H2 and H3+ abundances are very slow to appear and these same simple ideas of
      static equilibrium cannot explain any, but a few, of the simplest of the trace
      species, which are ubiquitously embedded in H2-bearing diffuse gases.

PMID- 17015376
TI  - Deuterium enhancement in H3+ in pre-stellar cores.
AB  - Deuterium enhancement of monodeuterated species has been recognized for more than
      30 years as a result of chemical fractionation that results from the difference
      in zero-point energies of deuterated and hydrogenated molecules. The key reaction
      is the deuteron exchange in the reaction between HD, the reservoir of deuterium
      in dark interstellar clouds, and the H3+ molecular ion, leading to the production
      of H2D+ molecule, and the low temperature in dark interstellar clouds favours
      this production. Furthermore, the presence of multiply deuterated species have
      incited our group to proceed further and consider the subsequent reaction of H2D+
      with HD, leading to D2H+, which can further react with HD to produce D3+. In pre
      stellar cores, where CO was found to be depleted, this production should be
      increased as CO would normally destroy H3+. The first model including D2H+ and
      D3+ predicted that these molecules should be as abundant as H2D+. The first
      detection of the D2H+ was made possible by the recent laboratory measurement for
      the frequency of the fundamental line of para-D2H+. Here, we present observations
      of H2D+ and D2H+ towards a sample of dark clouds and pre-stellar cores and show
      how the distribution of ortho-H2D+ (1(1,0)-1(1,1)) can trace the deuterium
      factory in pre-stellar cores. We also present how future instrumentation will
      improve our knowledge concerning the deuterium enhancement of H3+.

PMID- 17015377
TI  - Dissociative recombination of cold H3+ and its interstellar implications.
AB  - H3+ plays a key role in interstellar chemistry as the initiator of ion-molecule
      chemistry. The amount of H3+ observed in dense interstellar clouds is consistent
      with expectations, but the large abundance of H3+ seen in diffuse clouds is not
      easily explained by simple chemical models. A crucial parameter in predicting the
      abundance of H3+ in diffuse clouds is the rate constant for dissociative
      recombination (DR) with electrons. The value of this constant has been very
      controversial, because different experimental techniques have yielded very
      different results, perhaps owing to varying degrees of rotational and vibrational
      excitation of the H3+ ions. If the value of this rate constant under interstellar
      conditions were much lower than usually assumed, the large H3+ abundance could be
      easily explained. In an attempt to pin down this crucial rate constant, we have
      performed DR measurements at the CRYRING ion storage ring in Stockholm, using a
      supersonic expansion ion source to produce rotationally cold H3+ ions. These
      measurements suggest that the DR rate constant in diffuse clouds is not much
      lower than usually assumed and that the abundant H3+ must be due to either a low
      electron fraction or a high ionization rate.

PMID- 17015378
TI  - The role of asymptotic vibrational states in H3+.
AB  - Calculations are discussed which characterize all the vibrational bound states of
      the H3+ and D2H+ molecular ions using a realistic ab initio potential energy
      surface. Graphical analysis and calculation of rotational constants show that
      both ions support a series of atom-diatom-like long-range states: asymptotic
      vibrational states. The role of these states in the H3+ system and other
      molecules is discussed. The vibrational calculations are extended above
      dissociation where the resulting (Feshbach) resonances are shown to be too short
      lived to be of importance for the H3+ photodissociation spectrum.

PMID- 17015379
TI  - Ion-pair formation in electron recombination with H3+.
AB  - The process of resonant ion-pair formation following electron collisions with H3+
      is studied. The relevant diabatic potential energy surfaces and the electronic
      couplings between these surfaces are calculated. The reaction is then described
      using a time-dependent approach with wave packets propagating on the coupled
      potentials. In order to describe the reaction, it is found necessary to include
      at least two dimensions in the model. The effects of the Rydberg states on the
      cross-section for this process are discussed.

PMID- 17015380
TI  - Using H3+ and H2D+ as probes of star-forming regions.
AB  - The H3+ and H2D+ ions are important probes of the physical and chemical
      conditions in regions of the interstellar medium where new stars are forming.
      This paper reviews how observations of these species and of heavier ions such as
      HCO+ and H3O+ can be used to derive chemical and kinematic properties of nearby
      pre-stellar cores and the cosmic ray ionization rate towards more distant regions
      of high-mass star formation. Future prospects in the field are outlined at the
      end.

PMID- 17015382
TI  - H3+ in the electronic triplet state: current status.
AB  - We review the theoretical work carried out on the tri-hydrogen ion in the
      electronic triplet state 1(3)E', which is split into a3Sigma+u and 2(3)A' by
      vibronic interaction. We begin with an overview on analytical potential energy
      surfaces and calculations of rovibrational states by focusing on our own results,
      which are based on the most accurate potential energy surfaces available so far.
      This is followed by an examination of the selection rules and predictions of
      infrared transition frequencies. Finally, we discuss the Slonczewski resonance
      states supported by the upper sheet of the potential energy surface. Theoretical
      work reported here may be of interest for future experiments on the title ion.

PMID- 17015383
TI  - Deuterated H3+ as a probe of isotope fractionation in star-forming regions.
AB  - Observations of molecular D/H ratios in the interstellar medium are used to probe
      the physical conditions, such as temperature, ionization fraction and the
      importance of gas-grain reactions. In cold, dense regions, such as cores which
      are collapsing to form stars, the level of deuterium fractionation depends on the
      conversion of H3+ into its deuterated isotopologues (H2D+, D2H+ and D3+). The
      relative abundances of these molecules uniquely probe the centres of these cores
      where other, heavier, species have frozen onto dust grains. We present models of
      the deuterium chemistry close to the centre of a pre-stellar core, in the last
      stage before the star forms, showing the dependence of the observable molecular
      D/H ratios on the physical parameters and rate coefficients that are assumed. We
      compare model predictions with the latest observations of these regions.

PMID- 17015384
TI  - Spectro-imaging observations of H3+ on Jupiter.
AB  - Narrow-band filter, high-spectral-resolution (0.2 cm(-1)) spectro-imaging
      infrared observations of Jupiter's auroral zones, acquired in October 1999 and
      October 2000 with the FTS/BEAR instrument at the Canada-France-Hawaii Telescope,
      have provided maps of the emission from the H2 S1(1) quadrupole line and several
      H3+ lines. H2 and H3+ emissions appear to be morphologically different,
      especially in the north, where the latter notably exhibits a 'hot spot' near
      lambdaIII = 150-170 degrees System III longitude. The spectra include a total of
      14 H3+ lines, including two hot lines from the 3v2-v2 band, detected on Jupiter
      for the first time. They can be used to determine H3+ column densities,
      rotational (Trot) and vibrational (Tvib) temperatures. We find the mean Tvib of
      the v2 = 3 state to be lower (960 +/- 50 K) than the mean Trot in v2 = 2 (1170 +/
      75 K), indicating an underpopulation of the v2 = 3 level with respect to local
      thermodynamical equilibrium. Rotational temperatures and associated column
      densities are generally higher and lower, respectively, than inferred previously
      from v2 observations. These features can be explained by the combination of both
      a large positive temperature gradient in the sub-microbar auroral atmosphere and
      non-local thermal equilibrium effects affecting preferentially hot and
      combination bands. Spatial variations in line intensities are mostly owing to
      correlated variations in the H3+ column densities. The thermostatic role played
      by H3+ at ionospheric levels may provide an explanation. The exception is the
      northern 'hot spot', which exhibits a Tvib about 250 K higher than other regions.

PMID- 17015385
TI  - Models of H3+ in warm, diffuse, molecular gas in the Galactic centre.
AB  - Oka et al. (Oka et al. 2005 Astrophys. J. 632, 882-893) have recently observed a
      large column density of H3+ in the Galactic centre. In one of the gaseous
      components, a column density of H3+ in its metastable level (3,3) of
      approximately 4 x 10(14) cm(-2) is measured. From the excitation of H3+, they
      deduce a density below 50 cm(-3) and a temperature approximately 270 K. In this
      paper, we report results for this region from a new version of our PDR code which
      includes the H3+ excitation. Models show it is unlikely that the mean temperature
      of the gas could be above 100 K. We also show that there is a possibility to
      produce hot H3+ in C-shocks.

PMID- 17015386
TI  - Hyzone.
AB  - I discuss in this short paper the origin of the name 'hyzone' given to the
      molecules H3+ and H3, and how this name was forgotten, never to appear again in
      the scientific literature.

PMID- 17015387
TI  - Physics, chemistry and astronomy of H3+. Introductory remarks.

PMID- 17015388
TI  - Theoretical progress and challenges in H3+ dissociative recombination.
AB  - We discuss the Jahn-Teller mechanism for dissociative recombination in low energy
      collisions between electrons and H3+ ions, in energy ranges relevant to the
      processes underway in interstellar clouds. While theory has become capable of
      predicting recombination rates in reasonable agreement with storage ring
      experiments, some discrepancies remain with them, and a long-standing discrepancy
      with stationary afterglow measurements remains troubling. Speculations about the
      desirable improvements in both theory and experiment are presented.

PMID- 17015389
TI  - Near-infrared spectroscopy of H3+ above the barrier to linearity.
AB  - Since the Royal Society Discussion Meeting on H3+ in 2000, the laboratory
      spectroscopy of H3+ has entered a new regime. For the first time, transitions of
      H3+ above the barrier to linearity have been observed. A highly sensitive near
      infrared spectrometer based on a titanium:sapphire laser and incorporating a dual
      beam, double-modulation technique with bidirectional optical multi-passing has
      been developed in order to detect these transitions, which are more than 4600
      times weaker than the fundamental band. We discuss our recent work on the 2v1 +
      2v2(2) <-- 0, 3v1 + v2(1) <-- 0, v1 + 4v2(2) <-- 0, v1 + 4V2(4) <-- 0 and 2v1 +
      3v2(1) <-- 0 combination bands and the 5v2(1) <-- 0, 5v2(3) <-- 0, 52(5) <-- 0
      and 6v2(2) <-- 0 overtone bands. Experimentally determined energy levels provide
      a critical test of ab initio calculations in this challenging energy regime
      (greater than 10,000 cm(-1)). By comparing the experimental energy levels and
      theoretical energy levels from ab initio calculations in which the adiabatic and
      relativistic corrections are incorporated, the extent of higher-order effects
      such as non-adiabatic and radiative corrections is revealed.

PMID- 17015390
TI  - H3+ cooling in primordial gas.
AB  - Simulations of the thermal and dynamical evolution of primordial gas typically
      focus on the role played by H2 cooling. H2 is the dominant coolant in low-density
      primordial gas and it is usually assumed that it remains dominant at high
      densities. However, H2 is not an effective coolant at high densities, owing to
      the low critical density at which it reaches local thermodynamic equilibrium and
      to the large opacities that develop in its emission lines. It is therefore
      important to quantify the contribution made to the cooling rate by emission from
      the other molecules and ions present in the gas. A particularly interesting
      candidate is the H3+ ion, which is known to be an effective coolant at high
      densities in planetary atmospheres. In this paper, we present results from
      simulations of the thermal and chemical evolution of gravitationally collapsing
      primordial gas, which include a detailed treatment of H3+ chemistry and an
      approximate treatment of H3+ cooling. We show that in most cases, the
      contribution from H3+ is too small to be important, but if a sufficiently strong
      ionizing background is present, then H3+ cooling may become significant.

PMID- 17015391
TI  - Action spectroscopy of H3+ and D2H+ using overtone excitation.
AB  - The H3+ ion and its deuterated isotopologues H2D+, D2H+ and D3+ play an important
      role in astrophysical and laboratory plasmas. The main challenge for
      understanding these ions and their interaction at low temperatures are state
      specific experiments. This requires manipulation and a simple but efficient in
      situ characterization of their low-lying rotational states. In this contribution
      we report measurements of near infrared (NIR) absorption spectra. Required high
      sensitivity is achieved by combining liquid nitrogen cooled plasma with the
      technique of NIR cavity ringdown absorption spectroscopy. The measured transition
      frequencies are then used for exciting cold ions stored in a low-temperature 22
      pole radiofrequency ion trap. Absorption of a photon by the stored ion is
      detected by using the laser-induced reactions technique. As a monitor reaction,
      the endothermic proton (or deuteron) transfer to Ar is used in our studies. Since
      the formed ArH+ (or ArD+) ions are detected with near unit efficiency, the stored
      ions can be characterized very efficiently, even if there are just a few of them.

PMID- 17015392
TI  - Dynamical constraints and nuclear spin caused restrictions in HmD+ collision
      systems.
AB  - This contribution summarizes a variety of results and ongoing activities, which
      contribute to our understanding of inelastic and reactive collisions involving
      hydrogen ions. In an overview of our present theoretical knowledge of various
      HmD+ collision systems (m + n < or = 5), it is emphasized that although the
      required potential energy surfaces are well characterized, no detailed treatments
      of the collision dynamics are available to date, especially at the low energies
      required for astrochemistry. Instead of treating state-to-state dynamics with
      state of the art methods, predictions are still based on: (i) simple
      thermodynamical arguments, (ii) crude reaction models such as H atom exchange or
      proton jump, or (iii) statistical considerations used for describing processes
      proceeding via long-lived or strongly interacting collision complexes. A central
      problem is to properly account for the consequences of the fact that H and D are
      fermions and bosons, respectively. In the experimental and results sections, it
      is emphasized that although a variety of innovative techniques are available and
      have been used for measuring rate coefficients, cross-sections or state-to-state
      transition probabilities, the definitive experiments are still pending. In the
      centre of this contribution are our activities on various m + n = 5 systems. We
      report a few selected additional results for collisions of hydrogen ions with p
      H2, o-H2, HD, D2 or well-defined mixtures of these neutrals. Most of the recent
      experiments are based on temperature variable multipole ion traps and their
      combination with pulsed gas inlets, molecular beams, laser probing or electron
      beams. Based on the state-specific model calculations, it is concluded that for
      completely understanding the gas phase formation and destruction of HmDn+ in a
      trap, an in situ characterization of all the experimental parameters is required
      with unprecedented accuracy. Finally, the need to understand the hydrogen
      chemistry relevant for dense pre-stellar cores is discussed.

PMID- 17015393
TI  - H3+ towards and within the Galactic centre.
AB  - High-resolution spectroscopy of bright infrared sources in the centre of the
      Galaxy has resulted in the detection of H3+ in a remarkable array of dense and
      diffuse clouds along the 8000 parsec long line of sight, at a wide range of
      distances from the centre. Most prominent among these is a previously undetected,
      but very large amount of warm (T approximately 250 K) and diffuse (n
      approximately 100 cm2) gas within a few hundred parsecs of the centre. The key to
      understanding the environment of the H3+ in this region is an H3+ absorption line
      at 3.53 microm from the metastable (3,3) rotational level, which has not been
      detected in dense or diffuse clouds outside of the Galactic centre (GC). We have
      used spectroscopy of this line along with other lines of H3+ and CO to
      characterize all of the clouds along the line of sight to the GC. The high
      abundance of H3+ in the central few hundred parsecs implies an ionization rate
      there that is several times larger than estimated for diffuse clouds outside the
      GC, and nearly two orders of magnitude greater than originally predicted for
      diffuse clouds.

PMID- 17015394
TI  - Electron-impact rotational excitation of H3+: relevance for thermalization and
      dissociation dynamics.
AB  - Electrons are known to be efficient in rotationally exciting molecular ions in
      low-density astrophysical plasmas. Rotational excitation of molecular ions has
      also been shown to affect the measured values of dissociative recombination (DR)
      rate coefficients. Thus, electron collisions with H3+ are expected to play a
      significant role in thermalization and dissociation dynamics of this ion, both in
      the laboratory and in space. Using the molecular R-matrix method combined with
      the adiabatic-nuclei-rotation approximation, we have computed new rate
      coefficients for the rotational excitation of H3+ by electrons at temperatures
      from 10 to 10,000 K. De-excitation rates are found to amount to a few 10(-7) cm3
      s(-1) below 1000 K, i.e. comparable in magnitude to that of DR. In astrophysical
      environments where the electron fraction exceeds 10(-4), electron collisions are
      thus expected to contribute to the non-thermal rotational distribution of H3+.
      The competition between electron and neutral collisions is discussed in the
      context of recent observations of H3+ towards Galactic centre sources.

PMID- 17015395
TI  - Observations and models of deuterated H3+ in proto-planetary disks.
AB  - Young, gas-rich proto-planetary disks orbiting around solar-type young stars
      represent a crucial phase in disk evolution and planetary formation. Of
      particular relevance is to observationally track the evolution of the gas, which
      governs the overall evolution of the disk and is eventually dispersed. However,
      the bulk of the mass resides in the plane, which is so cold and dense that
      virtually all heavy-element-bearing molecules freeze out onto the dust grains and
      disappear from the gas phase. In this paper, we show that the ground-state ortho
      H2D+ transition is the best, if not the only, tracer of the disk-plane gas. We
      report the theoretical models of the chemical structure of the plane of the disk,
      where the deuterated forms of H3+, including H2D+, play a major role. We also
      compare the theoretical predictions with the observations obtained towards the
      disk of the young star DM Tau and show that the ionization rate is probably
      enhanced there, perhaps owing to the penetration of X-rays from the central
      object through the disk plane. We conclude by remarking that the ground-state
      ortho-H2D+ transition is such a powerful diagnostic that it may also reveal the
      matter in the dark halos of external galaxies, if it is hidden in cold, dense and
      small clouds, as several theories predict.

PMID- 17015396
TI  - Rotation-vibrational states of H3+ and the adiabatic approximation.
AB  - We discuss recent progress in the calculation and identification of rotation
      vibrational states of H3+ at intermediate energies up to 13,000 cm(-1). Our
      calculations are based on the potential energy surface of Cencek et al. which is
      of sub-microhartree accuracy. As this surface includes diagonal adiabatic and
      relativistic corrections to the fixed nuclei electronic energies, the remaining
      discrepancies between our calculated and experimental data should be due to the
      neglect of non-adiabatic coupling to excited electronic states in the
      calculations. To account for this, our calculated energy values were adjusted
      empirically by a simple correction formula. Based on our understanding of the
      adiabatic approximation, we suggest two new approaches to account for the off
      diagonal adiabatic correction, which should work; however, they have not been
      tested yet for H3+. Theoretical predictions made for the above-barrier energy
      region of recent experimental interest are accurate to 0.35 cm(-1) or better.

PMID- 17015401
TI  - Toxigenic Fusarium spp. as determinants of trichothecene mycotoxins in settled
      grain dust.
AB  - Trichothecenes are immunosuppressive mycotoxins produced mainly by Fusarium spp.
      and often are detected as natural contaminants of grain and other agricultural
      products. Exposure to trichothecenes through inhalation during grain work may
      represent possible health risks for grain farmers. We aimed, therefore, to
      investigate the level of Fusarium spp. and trichothecenes in settled grain dust
      collected during work on 92 Norwegian farms. Mycotoxins were determined by gas
      chromatography-mass spectrometry, whereas the Fusarium spp. were identified and
      quantified both by species-specific semiquantitative polymerase chain reaction
      (PCR) and by cultivation. All potential trichothecene-producing molds in the
      grain dust were quantified using a PCR assay specific for tri5, the gene coding
      for trichodiene synthase that catalyzes the first step in the trichothecene
      biosynthesis. We performed correlation analysis between mold-DNA and mycotoxins
      to assess whether the PCR-detected DNA could be used as indicators of the
      mycotoxins. The methodological problem of detecting small amounts of airborne
      mycotoxins during grain work may then be avoided. Whereas the trichothecene
      producing Fusarium species in grain dust could not be identified or quantified to
      a sufficient extent by cultivation, all investigated Fusarium spp. could be
      specifically detected by PCR and quantified from the DNA agarose gel band
      intensities. Furthermore, we observed a strong correlation between the
      trichothecenes HT-2 toxin (HT-2) or T-2 toxin (T-2) and DNA specific for tri5 (r
      = 0.68 for HT-2 and r = 0.50 for T-2; p < 0.001), F. langsethiae (r = 0.77 for HT
      2 and r = 0.59 for T-2; p < 0.001), or F. poae (r = 0.41 for HT-2 and r = 0.35
      for T-2; p < 0.001). However, only a moderate correlation was observed between
      the trichothecene deoxynivalenol (DON) and the combination of its producers, F.
      culmorum and F. graminearum (r = 0.24, p = 0.02), and no significant correlation
      was observed between DON and tri5. PCR clearly improved the detection of
      toxigenic Fusaria as potential sources of health risks for farmers inhaling grain
      dust during work, but the use of Fusarium-DNA as indicators for trichothecenes
      should be used cautiously.

PMID- 17015402
TI  - Interventions for prevention of post-operative atrial fibrillation and its
      complications after cardiac surgery: a meta-analysis.
AB  - AIMS: Atrial fibrillation (AF) is the most common complication after cardiac
      surgery. We aimed to evaluate, by meta-analysis, all randomized trials testing
      interventions for preventing AF. METHODS AND RESULTS: Ninety-four trials of
      prevention of post-operative AF were identified, by standard search methods, and
      analysed by standard meta-analysis techniques. All five commonly tested
      interventions, beta-blockers (BBs), sotalol, amiodarone, magnesium, and atrial
      pacing, were effective in preventing AF. The odds ratio (OR) for the effect of BB
      on the incidence of AF was 0.36 (95% CI 0.28-0.47, P<0.001), but after trials
      confounded by post-operative non-study BB withdrawal were excluded was 0.69 (95%
      CI 0.54-0.87, P=0.002). Sotalol reduced AF, compared with placebo (OR 0.34, 95%
      CI 0.26-0.45, P<0.001) and compared with conventional BB (OR 0.42, 95% CI 0.26
      0.65, P<0.001). Amiodarone reduced AF (OR 0.48, 95% CI 0.40-0.57, P<0.001).
      Magnesium (Mg) also had an effect (OR 0.57 95% CI 0.42-0.77) but there was
      significant heterogeneity (P<0.001), partly explained by concomitant BB. The
      effect of Mg with BB was less (OR 0.83, 95% CI 0.60-1.16). Pacing reduced AF (OR
      0.60, 95% CI 0.47-0.77, P<0.001), despite wide variations in techniques. Only
      amiodarone and pacing significantly reduced length of stay, average -0.60 days
      (95% CI -0.92 to -0.29) and -1.3 days (95% CI -2.55 to -0.08), respectively.
      Collectively, all treatments analysed together reduced stroke (OR 0.63, 95% CI
      0.41-0.98). Amiodarone was the only intervention that alone significantly reduced
      stroke rate (OR 0.54, 95% CI 0.30-0.95). CONCLUSION: All five interventions
      reduced the incidence of AF, though the effect of BBs is less than previously
      thought. The significant reductions in length of stay and stroke in meta-analysis
      suggest that there are worthwhile benefits from aggressive prevention. Larger
      studies to confirm these clinical benefits and evaluate their cost-effectiveness
      would be worthwhile.

PMID- 17015398
TI  - The Ferrier Lecture 1998. The molecular biology of consciousness investigated
      with genetically modified mice.
AB  - The question is raised of the relevance of experimental work with the mouse and
      some of its genetically modified individuals in the study of consciousness. Even
      if this species does not go far beyond the level of 'minimal consciousness', it
      may be a useful animal model to examine the elementary building blocks of
      consciousness using the methods of molecular biology jointly with investigations
      at the physiological and behavioural levels. These building blocks which are
      anticipated to be universally shared by higher organisms (from birds to humans)
      may include: (i) the access to multiple states of vigilance, like wakefulness,
      sleep, general anaesthesia, etc.; (ii) the capacity for global integration of
      several sensory and cognitive functions, together with behavioural flexibility
      resulting in what is referred to as exploratory behaviour, and possibly a minimal
      form of intentionality. In addition, the contribution of defined neuronal
      nicotinic receptors species to some of these processes is demonstrated and the
      data discussed within the framework of recent neurocomputational models for
      access to consciousness.

PMID- 17015403
TI  - Prognostic significance of functional mitral regurgitation after a first non-ST
      segment elevation acute coronary syndrome.
AB  - AIMS: The development of mitral regurgitation (MR) after an acute myocardial
      infarction (AMI) is a recognized and frequent complication and its negative
      impact on survival has been observed. However, few data exist regarding MR after
      non-ST-segment elevation acute coronary syndrome (NSTSEACS). Our aim was to
      investigate the incidence, clinical predictors, and prognostic implications of MR
      in the setting of NSTSEACS. METHODS AND RESULTS: We studied 300 consecutive
      patients (71.7% men, mean age 66.9+/-13 years) admitted to our coronary care unit
      for an NSTSEACS. Every patient underwent an echocardiographic study during the
      first week after the index NSTSEACS and was clinically followed up. MR was
      detected in 42% (126 patients; 88 men, mean age 71.3+/-11 years). Mean follow-up
      was 425.6+/-194.8 days. Only age and left ventricular (LV) ejection fraction (EF)
      were found as independent markers of the development of MR; no variable was found
      as an independent predictor of in-hospital mortality and only MR was found as an
      independent predictor of long-term outcome. CONCLUSION: MR is frequent after an
      NSTSEACS. Age and a low LV EF are factors associated to its development. The
      presence and degree of MR confer a worse long-term prognosis to patients after a
      first NSTSEACS. Thus, the presence of MR should be specifically assessed in every
      patient after an NSTSEACS.

PMID- 17015404
TI  - Diagnosis of aortic valvular stenosis by multislice cardiac computed tomography.
AB  - AIMS: Current improvements in spatial, temporal, and contrast resolution of
      multislice computed tomography (CT) could be useful in the assessment of valvular
      diseases. We evaluated the diagnostic accuracy of multislice CT for the
      identification and quantification of aortic valvular stenosis (AS), compared with
      echography. METHODS AND RESULTS: Consecutive patients, referred for coronary CT,
      were evaluated for AS, by the use of standard electrocardiography-gated 16-slice
      CT protocol. Multiplanar reformat was applied to systolic phases of the cardiac
      cycle, with projection on thick slices for measuring the aortic valvular area
      (AVA). CT results were compared with echocardiographic-based measurement of the
      AVA. Among 107 enrolled patients, CT analysis of the AVA was feasible in 103.
      Among the 30 patients with AS, Bland-Altman analysis showed good agreement
      between the two methods [mean difference -7 mm(2) (-40-25 mm(2))]. CONCLUSION: CT
      analysis of aortic valve is feasible in most cases and allows for reliable
      diagnosis and quantification of AS.

PMID- 17015405
TI  - Aspirin and clopidogrel resistance in patients with diabetes mellitus.

PMID- 17015406
TI  - Monitoring health risk behavior of Dutch adolescents and the development of
      health promoting policies and activities: the E-MOVO project.
AB  - This paper describes a new way of monitoring the health status of Dutch
      adolescents in order to stimulate the development of health policies at school
      and local levels and providing individual feedback using modern technology. The
      project is called E-MOVO that stands for Electronic Monitor and Health Education,
      in which seven Regional Health Authorities and the University of Maastricht
      collaborate. In this project, adolescents completed an electronic questionnaire
      via the Internet which measured topics related to demographics, school, physical
      health, mental health, well-being, lifestyle, criminality and leisure time
      activities. These data were used for feedback at three levels. On the basis of
      their answers, adolescents received tailored feedback on lifestyle in a personal
      'E-MOVO score', including links to relevant websites or other tailored
      information. The aggregated data were used to provide schools and municipalities
      with information on the health and well-being of their adolescent population.
      These data were used to encourage the development of health promoting policies
      and activities at both levels. This project was evaluated and is now adapted to
      implement at a national level.

PMID- 17015407
TI  - Ottawa to Bangkok: changing health promotion discourse.
AB  - The discourse of the 2005 Bangkok Charter for Health Promotion in a Globalized
      World represents a radical departure from that of the Ottawa Charter that, in
      1986, staked a place for the health promotion field in mainstream public health.
      Via a critical analysis of the discourse in these two Charters, this paper
      illustrates a shift from a 'new social movements' discourse of ecosocial justice
      in Ottawa to a 'new capitalist' discourse of law and economics in Bangkok. The
      Bangkok Charter's content may identify 'actions, commitments and pledges required
      to address the determinants of health in a globalized world through health
      promotion', but this paper shows how its discourse works to naturalize and
      perpetuate many of detrimental determinants associated with 'globalization'.

PMID- 17015408
TI  - Sleeping Beauty-based gene therapy with indoleamine 2,3-dioxygenase inhibits lung
      allograft fibrosis.
AB  - Sleeping Beauty (SB) transposon is a natural nonviral gene transfer system that
      can mediate long-term transgene expression. Its potential utility in treating
      organ transplantation-associated long-term complications has not yet been
      explored. In the present study we generated an improved SB transposon encoding
      the human gene indoleamine-2,3-dioxygenase (hIDO), an enzyme that possesses both
      T cell-suppressive and antioxidant properties and selectively delivered the SB
      transposon in combination with a hyperactive transposase plasmid to donor lung
      using the cationic polymer polyethylenimine (PEI) as transfection reagent. This
      nonviral gene therapeutic approach led to persistent and uniform transgene
      expression in the rat lung tissue without noticeable toxicity and inflammation.
      Importantly, IDO activity produced by hIDO transgene showed a remarkable
      therapeutic response, as evident by near normal pulmonary function (peak airway
      pressure and oxygenation), histological appearance, and reduced collagen content
      in lung allografts. In addition, we established a hIDO-overexpressing type II
      cell line using the SB-based gene transfer system and found that hIDO
      overexpressing lung cells effectively inhibited transforming growth factor-beta
      stimulated fibroblast proliferation in vitro. In summary, the SB-based gene
      therapy with hIDO represents a new strategy for treating lung transplantation
      associated chronic complications, e.g., obliterative bronchiolitis.

PMID- 17015409
TI  - Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor
      proliferation.
AB  - Cannabinoids, the active components of marijuana and their endogenous
      counterparts, act on the brain and many other organs through the widely expressed
      CB1 cannabinoid receptor. In contrast, the CB2 cannabinoid receptor is abundant
      in the immune system and shows a restricted expression pattern in brain cells.
      CB2-selective agonists are, therefore, very attractive therapeutic agents as they
      do not cause CB1-mediated psychoactive effects. CB2 receptor expression in brain
      has been partially examined in differentiated cells, while its presence and
      function in neural progenitor cells remain unknown. Here we show that the CB2
      receptor is expressed, both in vitro and in vivo, in neural progenitors from late
      embryonic stages to adult brain. Selective pharmacological activation of the CB2
      receptor in vitro promotes neural progenitor cell proliferation and neurosphere
      generation, an action that is impaired in CB2-deficient cells. Accordingly, in
      vivo experiments evidence that hippocampal progenitor proliferation is increased
      by administration of the CB2-selective agonist HU-308. Moreover, impaired
      progenitor proliferation was observed in CB2-deficient mice both in normal
      conditions and on kainate-induced excitotoxicity. These findings provide a novel
      physiological role for the CB2 cannabinoid receptor and open a novel therapeutic
      avenue for manipulating neural progenitor cell fate.

PMID- 17015410
TI  - Thrombin-activated platelets induce proliferation of human skin fibroblasts by
      stimulating autocrine production of insulin-like growth factor-1.
AB  - Platelet components have found successful clinical utilization to initiate or to
      accelerate tissue-repair mechanisms. However, the molecular pathways by which
      platelet factors contribute to tissue regeneration have not been fully
      elucidated. We have studied the effect of thrombin-activated platelets (TAPs) on
      cell growth in vivo and in cultured cell systems. Application of TAPs to
      ulcerative skin lesions of diabetic patients induced local activation of ERK1/2
      and Akt/PKB. Moreover, when applied to cultured human skin fibroblasts, TAPs
      promoted cell growth and DNA synthesis and activated platelet-derived growth
      factor (PDGF) and insulin-like growth factor (IGF)-1 receptor tyrosine kinases.
      PDGF was released by TAPs and rapidly achieved a plateau. At variance, the
      release of IGF-1 was mainly provided by the TAPs-stimulated fibroblasts and
      progressively increased up to 48 h. The PDGF-R blocker Ag1296 reduced the
      activation of Akt/PKB and, at a lesser extent, of ERK1/2. Conversely, inhibition
      of IGF-1 signaling by Ag1024 and expression of a dominant-negative IGF-1R mutant
      selectively reduced the stimulation of ERK1/2 by TAPs and fibroblast-released
      factors, with minor changes of Akt/PKB activity. Thus, platelet factors promote
      fibroblast growth by acutely activating Akt/PKB and ERK1/2. Sustained activation
      of ERK1/2, however, requires autocrine production of IGF-1 by TAPs-stimulated
      fibroblasts.

PMID- 17015411
TI  - Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes
      to the inflammation caused by Helicobacter pylori.
AB  - Gastric mucosal inflammation causes hypergastrinemia, and gastrin receptors have
      been detected in several leukocyte types. We have analyzed whether gastrin
      affects the leukocyte-endothelial cell interactions in vivo by monitoring
      leukocyte rolling, adhesion, and emigration in rat mesenteric venules using
      intravital microscopy. Mesenteric superfusion with exogenous gastrin increased
      these processes in a concentration- and time-dependent manner, effects prevented
      by the cholecystokinin (CCK)-2 receptor antagonists (proglumide, L-365,260) but
      not by the CCK-1 receptor antagonist devazepide. A similar response was induced
      by exogenous CCK or endogenously released gastrin. CCK-2 receptors were localized
      in mesenteric macrophages and polymorphonuclear leukocytes. This effect of
      gastrin is not modulated by somatostatin and is independent of the endogenous
      release of histamine. To analyze whether hypergastrinemia elicited by
      Helicobacter pylori (HP) modulates the inflammation induced by the germ, rats
      were chronically administered with an extract of a CagA+/VacA+ strain of HP. This
      protocol increased gastrinemia and induced an inflammatory response in the rat
      mesentery. Blockade of CCK-2 receptors attenuated this response and induced a
      qualitative change in the leukocyte infiltrate suggestive of a receding
      inflammatory process. Our results reveal a new proinflammatory role of gastrin
      that seems to contribute to the maintenance of the inflammation elicited by HP
      components.

PMID- 17015412
TI  - Developing models for patient flow and daily surge capacity research.
AB  - Between 1993 and 2003, visits to U.S. emergency departments (EDs) increased by
      26%, to a total of 114 million visits annually. At the same time, the number of
      U.S. EDs decreased by more than 400, and almost 200,000 inpatient hospital beds
      were taken out of service. In this context, the adequacy of daily surge capacity
      within the system is clearly an important issue. However, the research agenda on
      surge capacity thus far has focused primarily on large-scale disasters, such as
      pandemic influenza or a serious bioterrorism event. The concept of daily surge
      capacity and its relationship to the broader research agenda on patient flow is a
      relatively new area of investigation. In this article, the authors begin by
      describing the overlap between the research agendas on daily surge capacity and
      patient flow. Next, they propose two models that have potential applications for
      both daily surge capacity and hospitalwide patient-flow research. Finally, they
      identify potential research questions that are based on applications of the
      proposed research models.

PMID- 17015413
TI  - Improving surge capacity for biothreats: experience from Taiwan.
AB  - This article discusses Taiwan's experience in managing surge needs based on
      recent events, including the 1999 earthquake, severe acute respiratory syndrome
      in 2003, airliner crashes in 1998 and 2001, and yearly typhoons and floods.
      Management techniques are compared and contrasted with U.S. approaches. The
      authors discuss Taiwan's practices of sending doctors to the scene of an event
      and immediately recalling off-duty hospital personnel, managing volunteers,
      designating specialty hospitals, and use of incident management systems. The key
      differences in bioevents, including the mathematical myths regarding individual
      versus population care, division of stockpiles, the Maginot line, and multi
      jurisdictional responses, are highlighted. Several recent initiatives aimed at
      mitigating biothreats have begun in Taiwan, but their efficacy has not yet been
      tested. These include the integration of the emergency medical services and
      health-facility medical systems with other response systems; the use of the
      hospital emergency incident command system; crisis risk-communications
      approaches; and the use of practical, hands-on training programs. Other countries
      may gain valuable insights for mitigating and managing biothreats by studying
      Taiwan's experiences in augmenting surge capacity.

PMID- 17015414
TI  - The art and science of surge: experience from Israel and the U.S. military.
AB  - In a disaster or mass casualty incident, health care resources may be exceeded
      and systems may be challenged by unusual requirements. These resources may
      include pharmaceuticals, supplies, and equipment as well as certain types of
      academic and administrative expertise. New agencies and decision makers may need
      to work together in an unfamiliar environment. Furthermore, large numbers of
      casualties needing treatment, newer therapies required to care for these
      casualties, and increased workforce and space available for these casualties all
      contribute to what is often referred to as "surge." Surge capacity in emergency
      care can be described in technical, scientific terms that are measured by numbers
      and benchmarks (e.g., beds, patients, and medications) or can take on a more
      conceptual and abstract form (e.g., decisions, authority, and responsibility).
      The former may be referred to as the "science" of surge, whereas the latter, an
      equal if not more important component of surge systems that is more conceptual
      and abstract, can be considered the "art" of surge. The experiences from Israel
      and the U.S. military may serve to educate colleagues who may be required to
      respond or react to an event that taxes the current health care system. This
      report presents concrete examples of surge capacity strategies used by both
      Israel and the U.S. military and provides solutions that may be applied to other
      health care systems when faced with similar situations.

PMID- 17015415
TI  - Population-based triage management in response to surge-capacity requirements
      during a large-scale bioevent disaster.
AB  - Both the naturally occurring and deliberate release of a biological agent in a
      population can bring catastrophic consequences. Although these bioevents have
      similarities with other disasters, there also are major differences, especially
      in the approach to triage management of surge capacity resources. Conventional
      mass-casualty events use uniform methods for triage on the basis of severity of
      presentation and do not consider exposure, duration, or infectiousness, thereby
      impeding control of transmission and delaying recognition of victims requiring
      immediate care. Bioevent triage management must be population based, with the
      goal of preventing secondary transmission, beginning at the point of contact, to
      control the epidemic outbreak. Whatever triage system is used, it must first
      recognize the requirements of those Susceptible but not exposed, those Exposed
      but not yet infectious, those Infectious, those Removed by death or recovery, and
      those protected by Vaccination or prophylactic medication (SEIRV methodology).
      Everyone in the population falls into one of these five categories. This article
      addresses a population approach to SEIRV-based triage in which decision making
      falls under a two-phase system with specific measures of effectiveness to
      increase likelihood of medical success, epidemic control, and conservation of
      scarce resources.

PMID- 17015416
TI  - The creation of emergency health care standards for catastrophic events.
AB  - The creation of health care standards by the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO) in a defined area with known events follows a
      predictable process. A problem area (e.g., hand hygiene) is identified from
      multiple sources. The JCAHO then calls together experts from around the country,
      and through debate and the comparison of positions of various people within the
      health care arena, a new standard informed by these views can be developed. Once
      developed, it is vetted and becomes established as a Joint Commission standard.
      But what happens when an event has never happened, cannot be reliably predicted,
      and, one hopes, will never come to pass? How can one create any meaningful
      standards? This is the situation when considering a number of scenarios related
      to disasters and mass casualty events.

PMID- 17015418
TI  - Rescuer fatigue: standard versus continuous chest-compression cardiopulmonary
      resuscitation.
AB  - OBJECTIVES: Continuous chest-compression cardiopulmonary resuscitation (CCC-CPR)
      has been advocated as an alternative to standard CPR (STD-CPR). Studies have
      shown that CCC-CPR delivers substantially more chest compressions per minute and
      is easier to remember and perform than STD-CPR. One concern regarding CCC-CPR is
      that the rescuer may fatigue and be unable to maintain adequate compression rate
      or depth throughout an average emergency medical services response time. The
      specific aim of this study was to compare the effects of fatigue on the
      performance of CCC-CPR and STD-CPR on a manikin model. METHODS: This was a
      prospective, randomized crossover study involving 53 medical students performing
      CCC-CPR and STD-CPR on a manikin model. Students were randomized to their initial
      CPR group and then performed the other type of CPR after a period of at least two
      days. Students were evaluated on their performance of 9 minutes of CPR for each
      method. The primary endpoint was the number of adequate chest compressions (at
      least 38 mm of compression depth) delivered per minute during each of the 9
      minutes. The secondary endpoints were total compressions, compression rate, and
      the number of breaks taken for rest. The students' performance was evaluated on
      the basis of Skillreporter Resusci Anne (Laerdal, Wappingers Falls, NY)
      recordings. Primary and secondary endpoints were analyzed by using the
      generalized linear mixed model for counting data. RESULTS: In the first 2
      minutes, participants delivered significantly more adequate compressions per
      minute with CCC-CPR than STD-CPR, (47 vs. 32, p = 0.004 in the 1st minute and 39
      vs. 29, p = 0.04 in the 2nd minute). For minutes 3 through 9, the differences in
      number of adequate compressions between groups were not significant. Evaluating
      the 9 minutes of CPR as a whole, there were significantly more adequate
      compressions in CCC-CPR vs. STD-CPR (p = 0.0003). Although the number of adequate
      compressions per minute declined over time in both groups, the rate of decline
      was significantly greater in CCC-CPR compared with STD-CPR (p = 0.0003). The mean
      number of total compressions delivered in the first minute was significantly
      greater with CCC-CPR than STD-CPR (105 per minute vs. 58 per minute, p < 0.001)
      and did not change over 9 minutes in either group. There were no differences in
      compression rates or number of breaks between groups. CONCLUSIONS: CCC-CPR
      resulted in more adequate compressions per minute than STD-CPR for the first 2
      minutes of CPR. However, the difference diminished after 3 minutes, presumably as
      a result of greater rescuer fatigue with CCC-CPR. Overall, CCC-CPR resulted in
      more total compressions per minute than STD-CPR during the entire 9 minutes of
      resuscitation.

PMID- 17015417
TI  - Use of the Broselow tape may result in the underresuscitation of children.
AB  - OBJECTIVES: The purpose of this study was to determine the concordance of the
      Broselow tape with the measured heights and weights of a community-based
      population of children, especially in light of the increase in obesity in today's
      children. METHODS: The authors examined more than 7,500 children in a cross
      sectional, descriptive study in two different cohorts of children to compare
      their actual weight with their predicted weight by a color-coded tape measure.
      RESULTS: In all patients, the percent agreement and kappa values of the Broselow
      color predicted by height versus the actual color by weight for the 2002A tape
      were 66.2% and 0.61, respectively. The concordance was best in infants, followed
      by school-age children, toddlers, and preschoolers (kappa = 0.66, 0.44, 0.39, and
      0.39, respectively; percent agreement, 81.3%, 58.2%, 60.7%, and 64.0%,
      respectively). The tapes accurately predicted (within 10%) medication dosages for
      resuscitation in 55.3%-60.0% of the children. The number of children who were
      underdosed (by > or =10%) exceeded those who were overdosed (by > or =10%) by 2.5
      to 4.4 times (p < 0.05). The tapes accurately predicted uncuffed endotracheal
      tube sizes when compared with age-based guidelines in 71% of the children, with
      undersizing (> or =0.5 mm) exceeding oversizing by threefold to fourfold (p <
      0.05). CONCLUSIONS: The Broselow tape color-coded system inaccurately predicted
      actual weight in one third of children. Caregivers need to take into
      consideration the accuracy of this device when estimating children's weight
      during the resuscitation of a child.

PMID- 17015419
TI  - Developing a valid evaluation for interpersonal and communication skills.
AB  - OBJECTIVES: The Accreditation Council for Graduate Medical Education requires
      that residency programs evaluate the acquisition of six general competencies,
      including Interpersonal and Communication Skills (ICS). To develop a 360-degree
      method for accomplishing this, a semantic-differentiation matrix for various
      communication traits for nurses to evaluate physician ICS was developed. The
      authors sought to determine whether this evaluation method could discriminate
      between more experienced medical communicators (faculty) and less experienced
      medical communicators (residents). METHODS: A 98-item questionnaire measured
      several communication dimensions by using an eight-element semantic
      differentiation scale. In addition, global assessment ratings assessed nursing
      perceptions of physician ICS skills. This process was repeated for various
      clinical scenarios. RESULTS: There were 26 nurse evaluators, 19 emergency
      medicine (EM) residents (EM2 and EM3), and 30 EM faculty. Each physician received
      five independent evaluations (total, 245 evaluations). All EM residents (EM2 and
      EM3) were compared with the EM faculty. All eight items on the semantic
      differentiation scale were compared. Likewise, the global assessment scores were
      compared. In every category, the faculty scored higher (Mann-Whitney U: p <
      0.001). CONCLUSIONS: An evaluation process integrating a semantic-differentiation
      matrix was applied to various clinical scenarios (as well as global assessment
      items) and demonstrated discriminatory results. Faculty physicians scored
      significantly higher than resident physicians. The ability to provide
      discriminatory results is a requisite in the development of a valid evaluation
      process. The described semantic-differentiation matrix and global assessment
      questions may be valid measurements of ICS.

PMID- 17015420
TI  - The 2003 model of the clinical practice of emergency medicine: the 2005 update.

PMID- 17015421
TI  - IOM report: the future of emergency care in the United States health system.

PMID- 17015422
TI  - End-tidal carbon dioxide monitoring in the emergency department.

PMID- 17015423
TI  - Telomerase RNA level limits telomere maintenance in X-linked dyskeratosis
      congenita.
AB  - Dyskeratosis congenita (DC) patients suffer a progressive and ultimately fatal
      loss of hematopoietic renewal correlating with critically short telomeres. The
      predominant X-linked form of DC results from substitutions in dyskerin, a protein
      required both for ribosomal RNA (rRNA) pseudouridine modification and for
      cellular accumulation of telomerase RNA (TER). Accordingly, alternative models
      have posited that the exhaustion of cellular renewal in X-linked DC arises as a
      primary consequence of ribosome deficiency or telomerase deficiency. Here we
      test, for the first time, whether X-linked DC patient cells are compromised for
      telomerase function at telomeres. We show that telomerase activation in family
      matched control cells allows telomere elongation and telomere length maintenance,
      while telomerase activation in X-linked DC patient cells fails to prevent
      telomere erosion with proliferation. Furthermore, we demonstrate by phenotypic
      rescue that telomere defects in X-linked DC patient cells arise solely from
      reduced accumulation of TER. We also show that X-linked DC patient cells averted
      from premature senescence support normal levels of rRNA pseudouridine
      modification and normal kinetics of rRNA precursor processing, in contrast with
      phenotypes reported for a proposed mouse model of the human disease. These
      findings support the significance of telomerase deficiency in the pathology of X
      linked DC.

PMID- 17015424
TI  - MicroRNA-9a ensures the precise specification of sensory organ precursors in
      Drosophila.
AB  - MicroRNAs (miRNAs) have been implicated in regulating various aspects of animal
      development, but their functions in neurogenesis are largely unknown. Here we
      report that loss of miR-9a function in the Drosophila peripheral nervous system
      leads to ectopic production of sensory organ precursors (SOPs), whereas
      overexpression of miR-9a results in a severe loss of SOPs. We further demonstrate
      a strong genetic interaction between miR-9a and senseless (sens) in controlling
      the formation of SOPs in the adult wing imaginal disc. Moreover, miR-9a
      suppresses Sens expression through its 3' untranslated region. miR-9a is
      expressed in epithelial cells, including those adjacent to SOPs within proneural
      clusters, suggesting that miR-9a normally inhibits neuronal fate in non-SOP cells
      by down-regulating Sens expression. These results indicate that miR-9a ensures
      the generation of the precise number of neuronal precursor cells during
      development.

PMID- 17015425
TI  - The bHLH-PAS protein Spineless is necessary for the diversification of dendrite
      morphology of Drosophila dendritic arborization neurons.
AB  - Dendrites exhibit a wide range of morphological diversity, and their arborization
      patterns are critical determinants of proper neural connectivity. How different
      neurons acquire their distinct dendritic branching patterns during development is
      not well understood. Here we report that Spineless (Ss), the Drosophila homolog
      of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), regulates dendrite
      diversity in the dendritic arborization (da) sensory neurons. In loss-of-function
      ss mutants, class I and II da neurons, which are normally characterized by their
      simple dendrite morphologies, elaborate more complex arbors, whereas the normally
      complex class III and IV da neurons develop simpler dendritic arbors.
      Consequently, different classes of da neurons elaborate dendrites with similar
      morphologies. In its control of dendritic diversity among da neurons, ss likely
      acts independently of its known cofactor tango and through a regulatory program
      distinct from those involving cut and abrupt. These findings suggest that one
      evolutionarily conserved role for Ahr in neuronal development concerns the
      diversification of dendrite morphology.

PMID- 17015426
TI  - The right place at the right time: regulation of daily timing by phosphorylation.

PMID- 17015427
TI  - Gene regulatory networks for the development and evolution of the chordate heart.

PMID- 17015428
TI  - Neuronal polarity in CNS development.
AB  - The diversity of neuronal morphologies and the complexity of synaptic connections
      in the mammalian brain provide striking examples of cell polarity. Over the past
      decade, the identification of the PAR (for partitioning-defective) proteins,
      their function in polarity in the Caenorhabditis elegans zygote, and the
      conservation of polarity proteins related to the PAR polarity complex in
      Drosophila and vertebrates, kindled intense interest in polarity pathways.
      Although the existence of a conserved polarity protein complex does not prove
      that these proteins function the same way in different systems, the emergence of
      an evolutionarily conserved mechanism that regulates cell polarity provides an
      exciting opportunity to define the role of polarity proteins in the generation of
      the diverse array of cell types and patterns of connections in the developing
      mammalian brain. This review addresses emerging genetic, molecular genetic,
      biochemical, and cell biological approaches and mechanisms that control neuronal
      polarity, focusing on recent studies using the neonatal cerebellum and
      hippocampus as model systems.

PMID- 17015429
TI  - Hepatocytes with extensive telomere deprotection and fusion remain viable and
      regenerate liver mass through endoreduplication.
AB  - We report that mouse liver cells are highly resistant to extensive telomere
      dysfunction. In proliferating cells, telomere dysfunction results in chromosome
      end fusions, a DNA damage signal, and apoptosis or senescence. To determine the
      consequences of telomere dysfunction in noncycling cells, we used conditional
      deletion of the telomeric protein TRF2 in hepatocytes. TRF2 loss resulted in
      telomeric accumulation of gamma-H2AX and frequent telomere fusions, indicating
      telomere deprotection. However, there was no induction of p53 or apoptosis, and
      liver function appeared unaffected. Furthermore, the loss of TRF2 did not
      compromise liver regeneration after partial hepatectomy. Remarkably, liver
      regeneration occurred without cell division involving endoreduplication and cell
      growth, thereby circumventing the chromosome segregation problems associated with
      telomere fusions. We conclude that nondividing hepatocytes can maintain and
      regenerate liver function despite substantial loss of telomere integrity.

PMID- 17015430
TI  - Sox2 is required for development of taste bud sensory cells.
AB  - Sox2 is expressed in basal epithelial cells of the tongue, with high levels in
      taste bud placodes, fungiform papillae, and mature taste cells, and low levels in
      filiform papillae. High Sox2 expression appears to lie downstream from canonical
      Wnt signaling. In hypomorphic Sox2(EGFP/LP) embryos, placodes form but no mature
      taste buds develop. In contrast, transgenic overexpression of Sox2 in the basal
      cells inhibits differentiation of filiform keratinocytes. Together, our loss-of
      function and gain-of-function studies suggest that Sox2 functions in a dose
      dependent manner to regulate the differentiation of endodermal progenitor cells
      of the tongue into taste bud sensory cells versus keratinocytes.

PMID- 17015431
TI  - A positive feedback loop between the p53 and Lats2 tumor suppressors prevents
      tetraploidization.
AB  - Damage to the mitotic spindle and centrosome dysfunction can lead to cancer. To
      prevent this, cells trigger a succession of checkpoint responses, where an
      initial mitotic delay is followed by slippage without cytokinesis, spawning
      tetraploid G1 cells that undergo a p53-dependent G1/S arrest. We describe the
      importance of Lats2 (Large Tumor Suppressor 2) in this checkpoint response. Lats2
      binds Mdm2, inhibits its E3 ligase activity, and activates p53. Nocodazole, a
      microtubule poison that provokes centrosome/mitotic apparatus dysfunction,
      induces Lats2 translocation from centrosomes to the nucleus and p53 accumulation.
      In turn, p53 rapidly and selectively up-regulates Lats2 expression in G2/M cells,
      thereby defining a positive feedback loop. Abrogation of Lats2 promotes
      accumulation of polyploid cells upon exposure to nocodazole, which can be
      prevented by direct activation of p53. The Lats2-Mdm2-p53 axis thus constitutes a
      novel checkpoint pathway critical for the maintenance of proper chromosome
      number.

PMID- 17015432
TI  - Control of cellular senescence by CPEB.
AB  - Cytoplasmic polyadenylation element-binding protein (CPEB) is a sequence-specific
      RNA-binding protein that promotes polyadenylation-induced translation. While a
      CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts
      derived from this mouse (MEFs) do not enter senescence in culture as do wild-type
      MEFs, but instead are immortal. Exogenous CPEB restores senescence in the KO MEFs
      and also induces precocious senescence in wild-type MEFs. CPEB cannot stimulate
      senescence in MEFs lacking the tumor suppressors p53, p19ARF, or p16(INK4A);
      however, the mRNAs encoding these proteins are unlikely targets of CPEB since
      their expression is the same in wild-type and KO MEFs. Conversely, Ras cannot
      induce senescence in MEFs lacking CPEB, suggesting that it may lie upstream of
      CPEB. One target of CPEB regulation is myc mRNA, whose unregulated translation in
      the KO MEFs may cause them to bypass senescence. Thus, CPEB appears to act as a
      translational repressor protein to control myc translation and resulting cellular
      senescence.

PMID- 17015433
TI  - Cracking the egg: molecular dynamics and evolutionary aspects of the transition
      from the fully grown oocyte to embryo.
AB  - Fully grown oocytes (FGOs) contain all the necessary transcripts to activate
      molecular pathways underlying the oocyte-to-embryo transition (OET). To elucidate
      this critical period of development, an extensive survey of the FGO transcriptome
      was performed by analyzing 19,000 expressed sequence tags of the Mus musculus FGO
      cDNA library. Expression of 5400 genes and transposable elements is reported. For
      a majority of genes expressed in mouse FGOs, homologs transcribed in eggs of
      Xenopus laevis or Ciona intestinalis were found, pinpointing evolutionary
      conservation of most regulatory cascades underlying the OET in chordates. A large
      proportion of identified genes belongs to several gene families with oocyte
      restricted expression, a likely result of lineage-specific genomic duplications.
      Gene loss by mutation and expression in female germline of retrotransposed genes
      specific to M. musculus is documented. These findings indicate rapid
      diversification of genes involved in female reproduction. Comparison of the FGO
      and two-cell embryo transcriptomes demarcated the processes important for
      oogenesis from those involved in OET and identified novel motifs in maternal
      mRNAs associated with transcript stability. Discovery of oocyte-specific
      eukaryotic translation initiation factor 4E distinguishes a novel system of
      translational regulation. These results implicate conserved pathways underlying
      transition from oogenesis to initiation of development and illustrate how genes
      acquire and lose reproductive functions during evolution, a potential mechanism
      for reproductive isolation.

PMID- 17015434
TI  - FGF signaling delineates the cardiac progenitor field in the simple chordate,
      Ciona intestinalis.
AB  - Comprehensive gene networks in Ciona intestinalis embryos provide a foundation
      for characterizing complex developmental processes, such as the initial phases of
      chordate heart development. The basic helix-loop-helix regulatory gene Ci-Mesp is
      required for activation of cardiac transcription factors. Evidence is presented
      that Ci-Ets1/2, a transcriptional effector of receptor tyrosine kinase (RTK)
      signaling, acts downstream from Mesp to establish the heart field. Asymmetric
      activation of Ets1/2, possibly through localized expression of FGF9, drives heart
      specification within this field. During gastrulation, Ets1/2 is expressed in a
      group of four cells descended from two Mesp-expressing founder cells (the B7.5
      cells). After gastrulation, these cells divide asymmetrically; the smaller
      rostral daughters exhibit RTK activation (phosphorylation of ERK) and form the
      heart lineage while the larger caudal daughters form the anterior tail muscle
      lineage. Inhibition of RTK signaling prevents heart specification. Targeted
      inhibition of Ets1/2 activity or FGF receptor function also blocks heart
      specification. Conversely, application of FGF or targeted expression of
      constitutively active Ets1/2 (EtsVp16) cause both rostral and caudal B7.5
      lineages to form heart cells. This expansion produces an unexpected phenotype:
      transformation of a single-compartment heart into a functional multicompartment
      organ. We discuss these results with regard to the development and evolution of
      the multichambered vertebrate heart.

PMID- 17015436
TI  - The Vibrio harveyi quorum-sensing system uses shared regulatory components to
      discriminate between multiple autoinducers.
AB  - The quorum-sensing bacterium Vibrio harveyi produces and responds to three
      autoinducers (AIs), and this sensory information converges to control the
      expression of bioluminescence, biofilm formation, type III secretion (TTS), and
      protease production. The AIs are detected by cognate sensor histidine kinases
      that all relay phosphate to the shared response regulator LuxO. LuxO indirectly
      represses the master regulator of quorum sensing, LuxR, through the activation of
      multiple genes encoding small regulatory RNAs (called qrr genes for Quorum
      Regulatory RNA). Here we use differential fluorescence induction to identify 50
      quorum-sensing-controlled promoters. Some promoters only showed significant
      responses in the simultaneous presence of all three AIs, while others displayed
      substantial responses to the individual AIs. A differential response to each AI
      input state was also observed for qrr and luxR expression and LuxR protein
      production. Individual cell analyses revealed that, in each case, all the
      bacteria in the population respond in unison to the various AI inputs. We propose
      that the V. harveyi quorum-sensing transition is not switch-like but rather
      operates in a graded manner, and that this signaling arrangement, which uses
      shared regulatory proteins, nonetheless provides V. harveyi a mechanism to
      respond uniquely to different AI input states.

PMID- 17015435
TI  - Sustained Notch signaling in progenitors is required for sequential emergence of
      distinct cell lineages during organogenesis.
AB  - Mammalian organogenesis results from the concerted actions of signaling pathways
      in progenitor cells that induce a hierarchy of regulated transcription factors
      critical for organ and cell type determination. Here we demonstrate that
      sustained Notch activity is required for the temporal maintenance of specific
      cohorts of proliferating progenitors, which underlies the ability to specify late
      arising cell lineages during pituitary organogenesis. Conditional deletion of Rbp
      J, which encodes the major mediator of the Notch pathway, leads to premature
      differentiation of progenitor cells, a phenotype recapitulated by loss of the
      basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late
      (Pit1) lineage into the early (corticotrope) lineage. Notch signaling is required
      for maintaining expression of the tissue-specific paired-like homeodomain
      transcription factor, Prop1, which is required for generation of the Pit1
      lineage. Attenuation of Notch signaling is necessary for terminal differentiation
      in post-mitotic Pit1+ cells, and the Notch-repressed Pit1 target gene, Math3, is
      specifically required for maturation and proliferation of the GH-producing
      somatotrope. Thus, sustained Notch signaling in progenitor cells is required to
      prevent conversion of the late-arising cell lineages to early-born cell lineages,
      permitting specification of diverse cell types, a strategy likely to be widely
      used in mammalian organogenesis.

PMID- 17015437
TI  - Extent of modifications in human proteome samples and their effect on dynamic
      range of analysis in shotgun proteomics.
AB  - The complexity of the human proteome, already enormous at the organism level,
      increases further in the course of the proteome analysis due to in vitro sample
      evolution. Most of in vitro alterations can also occur in vivo as post
      translational modifications. These two types of modifications can only be
      distinguished a posteriori but not in the process of analysis, thus rendering
      necessary the analysis of every molecule in the sample. With the new software
      tool ModifiComb applied to MS/MS data, the extent of modifications was measured
      in tryptic mixtures representing the full proteome of human cells. The estimated
      level of 8-12 modified peptides per each unmodified tryptic peptide present at
      >or=1% level is approaching one modification per amino acid on average. This is a
      higher modification rate than was previously thought, posing an additional
      challenge to analytical techniques. The solution to the problem is seen in
      improving sample preparation routines, introducing dynamic range-adjusted
      thresholds for database searches, using more specific MS/MS analysis using high
      mass accuracy and complementary fragmentation techniques, and revealing peptide
      families with identification of additional proteins only by unfamiliar peptides.
      Extensive protein separation prior to analysis reduces the requirements on speed
      and dynamic range of a tandem mass spectrometer and can be a viable alternative
      to the shotgun approach.

PMID- 17015438
TI  - Uptake and utilization of lyso-phosphatidylethanolamine by Saccharomyces
      cerevisiae.
AB  - Phosphatidylethanolamine (PtdEtn) is synthesized by multiple pathways located in
      different subcellular compartments in yeast. Strains defective in the synthesis
      of PtdEtn via phosphatidylserine (PtdSer) synthase/decarboxylase are auxotrophic
      for ethanolamine, which must be transported into the cell and converted to
      phospholipid by the cytidinediphosphate-ethanolamine-dependent Kennedy pathway.
      We now demonstrate that yeast strains with psd1Delta psd2Delta mutations, devoid
      of PtdSer decarboxylases, import and acylate exogenous 1-acyl-2-hydroxyl-sn
      glycero-3-phosphoethanolamine (lyso-PtdEtn). Lyso-PtdEtn supports growth and
      replaces the mitochondrial pool of PtdEtn much more efficiently than and
      independently of PtdEtn derived from the Kennedy pathway. Deletion of both the
      PtdSer decarboxylase and Kennedy pathways yields a strain that is a stringent
      lyso-PtdEtn auxotroph. Evidence for the specific uptake of lyso-PtdEtn by yeast
      comes from analysis of strains harboring deletions of the aminophospholipid
      translocating P-type ATPases (APLTs). Elimination of the APLTs, Dnf1p and Dnf2p,
      or their noncatalytic beta-subunit, Lem3p, blocked the import of radiolabeled
      lyso-PtdEtn and resulted in growth inhibition of lyso-PtdEtn auxotrophs. In cell
      extracts, lyso-PtdEtn is rapidly converted to PtdEtn by an acyl-CoA-dependent
      acyltransferase. These results now provide 1) an assay for APLT function based on
      an auxotrophic phenotype, 2) direct demonstration of APLT action on a
      physiologically relevant substrate, and 3) a genetic screen aimed at finding
      additional components that mediate the internalization, trafficking, and
      acylation of exogenous lyso-phospholipids.

PMID- 17015439
TI  - A pentatricopeptide repeat protein is a site recognition factor in chloroplast
      RNA editing.
AB  - In higher plants, RNA editing is a post-transcriptional process that converts C
      to U in organelle mRNAs. We have previously shown that an Arabidopsis thaliana
      crr4 mutant is defective with respect to RNA editing for creating the
      translational initial codon of the plastid ndhD gene (the ndhD-1 site). CRR4
      contains 11 pentatricopeptide repeat motifs but does not contain any domains that
      are likely to be involved in the editing activity. The green fluorescent protein
      fused to the putative transit peptide of CRR4 targeted the plastid. The
      recombinant CRR4 expressed in Escherichia coli specifically bound to the 25
      nucleotides of the upstream and the 10 nucleotides of the downstream sequences
      surrounding the editing site of ndhD-1. The target C nucleotide of this editing
      is not essential for the binding of CRR4. Taken together with the genetic
      evidence, we conclude that the pentatricopeptide repeat protein CRR4 is a
      sequence-specific RNA-binding protein that acts as a site recognition factor in
      plastid RNA editing.

PMID- 17015440
TI  - Analysis of human phagocyte flavocytochrome b(558) by mass spectrometry.
AB  - The catalytic core of the phagocyte NADPH oxidase is a heterodimeric integral
      membrane protein (flavocytochrome b (Cyt b)) that generates superoxide and
      initiates a cascade of reactive oxygen species critical for the host inflammatory
      response. In order to facilitate structural characterization, the present study
      reports the first direct analysis of human phagocyte Cyt b by matrix-assisted
      laser desorption/ionization and nanoelectrospray mass spectrometry. Mass analysis
      of in-gel tryptic digest samples provided 73% total sequence coverage of the
      gp91(phox) subunit, including three of the six proposed transmembrane domains.
      Similar analysis of the p22(phox) subunit provided 72% total sequence coverage,
      including assignment of the hydrophobic N-terminal region and residues that are
      polymorphic in the human population. To initiate mass analysis of Cyt b post
      translational modifications, the isolated gp91(phox) subunit was subject to
      sequential in-gel digestion with Flavobacterium meningosepticum peptide N
      glycosidase F and trypsin, with matrix-assisted laser desorption/ionization and
      liquid chromatography-mass spectrometry/mass spectrometry used to demonstrate
      that Asn-132, -149, and -240 are genuinely modified by N-linked glycans in human
      neutrophils. Since the PLB-985 cell line represents an important model system for
      analysis of the NADPH oxidase, methods were developed for the purification of Cyt
      b from PLB-985 membrane fractions in order to confirm the appropriate
      modification of N-linked glycosylation sites on the recombinant gp91(phox)
      subunit. This study reports extensive sequence coverage of the integral membrane
      protein Cyt b by mass spectrometry and provides analytical methods that will be
      useful for evaluating posttranslational modifications involved in the regulation
      of superoxide production.

PMID- 17015441
TI  - The cold and menthol receptor TRPM8 contains a functionally important double
      cysteine motif.
AB  - We have investigated the glycosylation, disulfide bonding, and subunit structure
      of mouse TRPM8. To do this, amino-terminal c-myc or hemagglutinin epitope-tagged
      proteins were incorporated and expressed in Chinese hamster ovary cells. These
      modifications had no obvious effects on channel function in intracellular calcium
      imaging assays upon application of agonists, icilin or menthol, and cold
      temperatures. Unmodified TRPM8 migrates with an apparent mass of 129 kDa and can
      be glycosylated in Chinese hamster ovary cells to give glycoproteins with
      apparent masses of 136 and 147 kDa. We identified two potential N-linked
      glycosylation sites in TRPM8 (Asn-821 and Asn-934) and mutated them to show that
      only the site in the putative pore region at position 934 is modified and that
      glycosylation of this site is not absolutely necessary for cell surface
      expression or responsiveness to icilin, menthol, and cool temperatures. Enzymatic
      cleavage of the carbohydrate chains indicated that they are complex carbohydrate.
      The glycosylation site is flanked in the pore by two cysteine residues that we
      mutated, to prove that they are involved in a conserved double cysteine motif,
      which is essential for channel function. Mutation of either of these cysteines
      abolishes function and forces the formation of a non-functional complex of the
      size of a homodimer. The double cysteine mutant is also non-functional. Finally,
      we showed in Perfluoro-octanoic acid-polyacrylamide gels that TRPM8 can form a
      tetramer (in addition to dimer and trimer forms), consistent with current
      thinking that functional TRP ion channels are tetrameric.

PMID- 17015443
TI  - Mapping the functional domains of yeast NMD3, the nuclear export adapter for the
      60 S ribosomal subunit.
AB  - Nuclear export of the large ribosomal subunit requires the adapter protein Nmd3p
      to provide a leucine-rich nuclear export signal that is recognized by the export
      receptor Crm1. Nmd3p binds to the pre-60 S subunit in the nucleus. After export
      to the cytoplasm, the release of Nmd3p depends on the ribosomal protein Rpl10p
      and the GTPase Lsg1p. Here, we have carried out a mutational analysis of Nmd3 to
      better define the domains responsible for nucleocytoplasmic shuttling and
      ribosome binding. We show that mutations in two regions of Nmd3p affect 60 S
      binding, suggesting that its binding to the subunit is multivalent.

PMID- 17015442
TI  - Saccharomyces cerevisiae Sit4 phosphatase is active irrespective of the nitrogen
      source provided, and Gln3 phosphorylation levels become nitrogen source
      responsive in a sit4-deleted strain.
AB  - Tor1,2 control of type 2A-related phosphatase activities in Saccharomyces
      cerevisiae has been reported to be responsible for the regulation of Gln3
      phosphorylation and intracellular localization in response to the nature of the
      nitrogen source available. According to the model, excess nitrogen stimulates
      Tor1,2 to phosphorylate Tip41 and/or Tap42. Tap42 then complexes with and
      inactivates Sit4 phosphatase, thereby preventing it from dephosphorylating Gln3.
      Phosphorylated Gln3 complexes with Ure2 and is sequestered in the cytoplasm. When
      Tor1,2 kinase activities are inhibited by limiting nitrogen, or rapamycin
      treatment, Tap42 can no longer complex with Sit4. Active Sit4 dephosphorylates
      Gln3, which can then localize to the nucleus and activate transcription. The
      paucity of experimental data directly correlating active Sit4 and Pph3 with Gln3
      regulation prompted us to assay Gln3-Myc(13) phosphorylation and intracellular
      localization in isogenic wild type, sit4, pph3, and sit4pph3 deletion strains. We
      found that Sit4 actively brought about Gln3-Myc(13) dephosphorylation in both
      good (glutamine or ammonia) and poor (proline) nitrogen sources. This Sit4
      activity masked nitrogen source-dependent changes in Gln3-Myc(13) phosphorylation
      which were clearly visible when SIT4 was deleted. The extent of Sit4 requirement
      for Gln3 nuclear localization was both nitrogen source- and strain-dependent. In
      some strains, Sit4 was not even required for Gln3 nuclear localization in
      untreated or rapamycin-treated, proline-grown cells or Msx-treated, ammonia-grown
      cells.

PMID- 17015444
TI  - Link between mitochondria and NADPH oxidase 1 isozyme for the sustained
      production of reactive oxygen species and cell death.
AB  - Although mitochondria and the Nox family of NADPH oxidase are major sources of
      reactive oxygen species (ROS) induced by external stimuli, there is limited
      information on their functional relationship. This study has shown that serum
      withdrawal promotes the production of ROS in human 293T cells by stimulating both
      the mitochondria and Nox1. An analysis of their relationship revealed that the
      mitochondria respond to serum withdrawal within a few minutes, and the ROS
      produced by the mitochondria trigger Nox1 action by stimulating phosphoinositide
      3-kinase (PI3K) and Rac1. Activation of the PI3K/Rac1/Nox1 pathway was evident 4
      8 h after but not earlier than serum withdrawal initiation, and this time lag was
      found to be required for an additional activator of the pathway, Lyn, to be
      expressed. Functional analysis suggested that, although the mitochondria
      contribute to the early (0-4 h) accumulation of ROS, the maintenance of the
      induced ROS levels to the later (4-8 h) phase required the action of the
      PI3K/Rac1/Nox1 pathway. Serum withdrawal-treated cells eventually lost their
      viability, which was reversed by blocking either the mitochondria-dependent
      induction of ROS using rotenone or KCN or the PI3K/Rac1/Nox1 pathway using the
      dominant negative mutants or small interfering RNAs. This suggests that
      mitochondrial ROS are essential but not enough to promote cell death, which
      requires the sustained accumulation of ROS by the subsequent action of Nox1.
      Overall, this study shows a signaling link between the mitochondria and Nox1,
      which is crucial for the sustained accumulation of ROS and cell death in serum
      withdrawal-induced signaling.

PMID- 17015445
TI  - A second fatty acid amide hydrolase with variable distribution among placental
      mammals.
AB  - Fatty acid amides constitute a large and diverse class of lipid transmitters that
      includes the endogenous cannabinoid anandamide and the sleep-inducing substance
      oleamide. The magnitude and duration of fatty acid amide signaling are controlled
      by enzymatic hydrolysis in vivo. Fatty acid amide hydrolase (FAAH) activity in
      mammals has been primarily attributed to a single integral membrane enzyme of the
      amidase signature (AS) family. Here, we report the functional proteomic discovery
      of a second membrane-associated AS enzyme in humans that displays FAAH activity.
      The gene that encodes this second FAAH enzyme was found in multiple primate
      genomes, marsupials, and more distantly related vertebrates, but, remarkably, not
      in a number of lower placental mammals, including mouse and rat. The two human
      FAAH enzymes, which share 20% sequence identity and are referred to hereafter as
      FAAH-1 and FAAH-2, hydrolyzed primary fatty acid amide substrates (e.g. oleamide)
      at equivalent rates, whereas FAAH-1 exhibited much greater activity with N-acyl
      ethanolamines (e.g. anandamide) and N-acyl taurines. Both enzymes were sensitive
      to the principal classes of FAAH inhibitors synthesized to date, including O-aryl
      carbamates and alpha-keto heterocycles. These data coupled with the overlapping,
      but distinct tissue distributions of FAAH-1 and FAAH-2 suggest that these
      proteins may collaborate to control fatty acid amide catabolism in primates. The
      apparent loss of the FAAH-2 gene in some lower mammals should be taken into
      consideration when extrapolating genetic or pharmacological findings on the fatty
      acid amide signaling system across species.

PMID- 17015446
TI  - A R2R3 type MYB transcription factor is involved in the cold regulation of CBF
      genes and in acquired freezing tolerance.
AB  - Cold temperatures trigger the expression of the CBF family of transcription
      factors, which in turn activate many downstream genes that confer freezing
      tolerance to plants. It has been shown previously that the cold regulation of
      CBF3 involves an upstream bHLH-type transcription factor, ICE1. ICE1 binds to the
      Myc recognition sequences in the CBF3 promoter. Apart from Myc recognition
      sequences, CBF promoters also have Myb recognition sequences. We report here that
      the Arabidopsis MYB15 is involved in cold-regulation of CBF genes and in the
      development of freezing tolerance. The MYB15 gene transcript is up-regulated by
      cold stress. The MYB15 protein interacts with ICE1 and binds to Myb recognition
      sequences in the promoters of CBF genes. Overexpression of MYB15 results in
      reduced expression of CBF genes whereas its loss-of-function leads to increased
      expression of CBF genes in the cold. The myb15 mutant plants show increased
      tolerance to freezing stress whereas its overexpression reduces freezing
      tolerance. Our results suggest that MYB15 is part of a complex network of
      transcription factors controlling the expression of CBFs and other genes in
      response to cold stress.

PMID- 17015447
TI  - Versatility and differential roles of cysteine residues in human prostacyclin
      receptor structure and function.
AB  - Prostacyclin plays important roles in vascular homeostasis, promoting
      vasodilatation and inhibiting platelet thrombus formation. Previous studies have
      shown that three of six cytoplasmic cysteines, particularly those within the C
      terminal tail, serve as important lipidation sites and are differentially
      conjugated to palmitoyl and isoprenyl groups (Miggin, S. M., Lawler, O. A., and
      Kinsella, B. T. (2003) J. Biol. Chem. 278, 6947-6958). Here we report distinctive
      roles for extracellular- and transmembrane-located cysteine residues in human
      prostacyclin receptor structure-function. Within the extracellular domain, all
      cysteines (4 of 4) appear to be involved in disulfide bonding interactions (i.e.
      a highly conserved Cys-92-Cys-170 bond and a putative non-conserved Cys-5-Cys-165
      bond), and within the transmembrane (TM) region there are several cysteines (3 of
      8) that maintain critical hydrogen bonding interactions (Cys-118 (TMIII), Cys-251
      (TMVI), and Cys-202 (TMV)). This study highlights the necessity of sulfhydryl
      (SH) groups in maintaining the structural integrity of the human prostacyclin
      receptor, as 7 of 12 extracellular and transmembrane cysteines studied were found
      to be differentially indispensable for receptor binding, activation, and/or
      trafficking. Moreover, these results also demonstrate the versatility and
      reactivity of these cysteine residues within different receptor environments,
      that is, extracellular (disulfide bonds), transmembrane (H-bonds), and
      cytoplasmic (lipid conjugation).

PMID- 17015448
TI  - Tuning of a neuronal calcium sensor.
AB  - Recoverin is a Ca(2+)-regulated signal transduction modulator expressed in the
      vertebrate retina that has been implicated in visual adaptation. An intriguing
      feature of recoverin is a cluster of charged residues at its C terminus, the
      functional significance of which is largely unclear. To elucidate the impact of
      this segment on recoverin structure and function, we have investigated a mutant
      lacking the C-terminal 12 amino acids. Whereas in myristoylated recoverin the
      truncation causes an overall decrease in Ca(2+) sensitivity, results for the non
      myristoylated mutant indicate that the truncation primarily affects the high
      affinity EF-hand 3. The three-dimensional structure of the mutant has been
      determined by x-ray crystallography. In addition to significant changes in
      average coordinates compared with wild-type recoverin, the structure provides
      strong indication of increased conformational flexibility, particularly in the C
      terminal domain. Based on these observations, we propose a novel role of the C
      terminal segment of recoverin as an internal modulator of Ca(2+) sensitivity.

PMID- 17015449
TI  - MAPK-activated protein kinase-2 (MK2)-mediated formation and phosphorylation
      regulated dissociation of the signal complex consisting of p38, MK2, Akt, and
      Hsp27.
AB  - The p38 MAPK and heat shock protein 27 (hsp27) form a signaling complex with
      serine/threonine kinase Akt and MAPK-activated protein kinase-2 (MK2), which
      plays an important role in controlling stress-induced apoptosis and reorganizing
      actin cytoskeleton. However, regulation of the complex is poorly understood. In
      this study, the interaction between p38 and hsp27 was visualized in single living
      L929 cells using fluorescence resonance energy transfer technology, while their
      association with Akt was examined by immunoprecipitation analysis. Under normal
      growth conditions, p38 kinase constitutively interacts with hsp27. When cells
      were exposed to H(2)O(2) or stimulated by arachidonic acid, this interaction was
      disrupted. However, inhibition of the activation of p38 and Akt by selective
      inhibitors or overexpression of the kinase-dead mutant of p38 diminished such
      effects. Furthermore, mutation of phosphorylation sites of hsp27 renders the
      interaction resistant to H(2)O(2) and arachidonic acid. It was interesting to
      find that the interaction disappeared in the cells from MK2-knock-out mice or the
      cells treated with lemptomycin B that blocks export of MK2 from nucleus to
      cytosol. However, MK2 is not required for the association of hsp27 with Akt. This
      study suggests that MK2 mediates the incorporation of p38 into the pre-existing
      complex of hsp27 with Akt. Phosphorylation of hsp27 finally breaks the signaling
      complex.

PMID- 17015450
TI  - Roles of Asp75, Asp78, and Glu83 of GTP-dependent phosphoenolpyruvate
      carboxykinase from Mycobacterium smegmatis.
AB  - The roles of Asp(75), Asp(78), and Glu(83) of the (75)DPSDVARVE(83) element of
      Mycobacterium smegmatis GTP-dependent phosphoenolpyruvate (PEP) carboxykinase
      (GTP-PEPCK) were investigated. Asp(78) and Glu(83) are fully conserved in GTP-PEP
      CKs. The human PEPCK crystal structure suggests that Asp(78) influences Tyr(220);
      Tyr(220) helps to position bound PEP, and Glu(83) interacts with Arg(81).
      Experimental data on other PEPCKs indicate that Arg(81) binds PEP, and the
      phosphate of PEP interacts with Mn(2+) of metal site 1 for catalysis. We found
      that D78A and E83A replacements severely reduced activity. E83A substitution
      raised the apparent K(m) value for Mn(2+) 170-fold. In contrast, Asp(75) is
      highly but not fully conserved; natural substitutions are Ala, Asn, Gln, or Ser.
      Such substitutions, when engineered, in M. smegmatis enzyme caused the following.
      1) For oxaloacetate synthesis, V(max) decreased 1.4-4-fold. K(m) values for PEP
      and Mn(2+) increased 3-9- and 1.2-10-fold, respectively. K(m) values for GDP and
      bicarbonate changed little. 2) For PEP formation, V(max) increased 1.5-2.7-fold.
      K(m) values for oxaloacetate increased 2-2.8-fold. The substitutions did not
      change the secondary structure of protein significantly. The kinetic effects are
      rationalized as follows. In E83A the loss of Glu(83)-Arg(81) interaction affected
      Arg(81)-PEP association. D78A change altered the Tyr(220)-PEP interaction. These
      events perturbed PEP-Mn(2+) interaction and consequently affected catalysis
      severely. In contrast, substitutions at Asp(75), a site far from bound PEP,
      brought subtle effects, lowering oxaloacetate formation rate but enhancing PEP
      formation rate. It is likely that Asp(75) substitutions affected PEP-Mn(2+)
      interaction by changing the positions of Asp(78), Arg(81), and Glu(83), which
      translated to differential effects on two directions.

PMID- 17015451
TI  - Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both
      ligand-dependent and -independent coordinated alterations of receptor
      localization and function.
AB  - Following inducible expression in HEK293 cells, the human orexin-1 receptor was
      targeted to the cell surface but became internalized following exposure to the
      peptide agonist orexin A. By contrast, constitutive expression of the human
      cannabinoid CB1 receptor resulted in a predominantly punctate, intracellular
      distribution pattern consistent with spontaneous, agonist-independent
      internalization. Expression of the orexin-1 receptor in the presence of the CB1
      receptor resulted in both receptors displaying the spontaneous internalization
      phenotype. Single cell fluorescence resonance energy transfer imaging indicated
      the two receptors were present as heterodimers/oligomers in intracellular
      vesicles. Addition of the CB1 receptor antagonist SR-141716A to cells expressing
      only the CB1 receptor resulted in re-localization of the receptor to the cell
      surface. Although SR-141716A has no significant affinity for the orexin-1
      receptor, in cells co-expressing the CB1 receptor, the orexin-1 receptor was also
      re-localized to the cell surface by treatment with SR-141716A. Treatment of cells
      co-expressing the orexin-1 and CB1 receptors with the orexin-1 receptor
      antagonist SB-674042 also resulted in re-localization of both receptors to the
      cell surface. Treatment with SR-141716A resulted in decreased potency of orexin A
      to activate the mitogen-activated protein kinases ERK1/2 only in cells co
      expressing the two receptors. Treatment with SB-674042 also reduced the potency
      of a CB1 receptor agonist to phosphorylate ERK1/2 only when the two receptors
      were co-expressed. These studies introduce an entirely novel pharmacological
      paradigm, whereby ligands modulate the function of receptors for which they have
      no significant inherent affinity by acting as regulators of receptor
      heterodimers.

PMID- 17015452
TI  - Spontaneous formation of L-isoaspartate and gain of function in fibronectin.
AB  - Isoaspartate formation in extracellular matrix proteins, by aspartate
      isomerization or asparagine deamidation, is generally viewed as a degradation
      reaction occurring in vivo during tissue aging. For instance, non-enzymatic
      isoaspartate formation at RGD-integrin binding sites causes loss of cell adhesion
      sites, which in turn can be enzymatically "repaired" to RGD by protein-l-isoAsp-O
      methyltransferase. We show here that isoaspartate formation is also a mechanism
      for extracellular matrix activation. In particular, we show that deamidation of
      Asn263 at the Asn-Gly-Arg (NGR) site in fibronectin N-terminal region generates
      an alpha(v)beta3-integrin binding site containing the L-isoDGR sequence, which is
      enzymatically "deactivated" to DGR by protein-L-isoAsp-O-methyltransferase.
      Furthermore, rapid NGR-to-isoDGR sequence transition in fibronectin fragments
      generates alpha(v)beta3 antagonists (named "isonectins") that competitively bind
      RGD binding sites and inhibit endothelial cell adhesion, proliferation, and tumor
      growth. Time-dependent generation of isoDGR may represent a sort of molecular
      clock for activating latent integrin binding sites in proteins.

PMID- 17015453
TI  - Disruption of tight junctions and induction of proinflammatory cytokine responses
      in colonic epithelial cells by Campylobacter jejuni.
AB  - Campylobacter jejuni is a leading cause of human enterocolitis and is associated
      with postinfectious complications, including irritable bowel syndrome and
      Guillain-Barre syndrome. However, the pathogenesis of C. jejuni infection remains
      poorly understood. Paracellular pathways in intestinal epithelial cells are gated
      by intercellular junctions (tight junctions and adherens junctions), providing a
      functional barrier between luminal microbes and host immune cells in the lamina
      propria. Here we describe alterations in tight junctions in intestinal epithelial
      monolayers following C. jejuni infection. Apical infection of polarized T84
      monolayers caused a time-dependent decrease in transepithelial electrical
      resistance (TER). Immunofluorescence microscopy revealed a redistribution of the
      tight junctional transmembrane protein occludin from an intercellular to an
      intracellular location. Subcellular fractionation using equilibrium sucrose
      density gradients demonstrated decreased hyperphosphorylated occludin in lipid
      rafts, Triton X-100-soluble fractions, and the Triton X-100-insoluble pellet
      following apical infection. Apical infection with C. jejuni also caused rapid
      activation of NF-kappaB and AP-1, phosphorylation of extracellular signal
      regulated kinase, Jun N-terminal protein kinase, and p38 mitogen-activated
      protein kinases, and basolateral secretion of the CXC chemokine interleukin-8 (IL
      8). Basolateral infection with C. jejuni caused a more rapid decrease in TER,
      comparable redistribution of tight-junction proteins, and secretion of more IL-8
      than that seen with apical infection. These results suggest that compromised
      barrier function and increased chemokine expression contribute to the
      pathogenesis of C. jejuni-induced enterocolitis.

PMID- 17015454
TI  - Proinflammatory and antimicrobial nitric oxide in gingival fluid of diabetic
      patients with periodontal disease.
AB  - Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of
      both periodontal disease and diabetes mellitus. In diabetic patients, increased
      inducible NO synthase in inflamed gingiva correlated with NO in gingival
      crevicular fluid. Although increased NO reflected more-severe inflammation, it
      was associated with reductions in CFU of Prevotella intermedia, a major
      periodontopathogen, highlighting dual roles for NO.

PMID- 17015455
TI  - Mutation of the maturase lipoprotein attenuates the virulence of Streptococcus
      equi to a greater extent than does loss of general lipoprotein lipidation.
AB  - Streptococcus equi is the causative agent of strangles, a prevalent and highly
      contagious disease of horses. Despite the animal suffering and economic burden
      associated with strangles, little is known about the molecular basis of S. equi
      virulence. Here we have investigated the contributions of a specific lipoprotein
      and the general lipoprotein processing pathway to the abilities of S. equi to
      colonize equine epithelial tissues in vitro and to cause disease in both a mouse
      model and the natural host in vivo. Colonization of air interface organ cultures
      after they were inoculated with a mutant strain deficient in the maturase
      lipoprotein (DeltaprtM(138-213), with a deletion of nucleotides 138 to 213) was
      significantly less than that for cultures infected with wild-type S. equi strain
      4047 or a mutant strain that was unable to lipidate preprolipoproteins
      (Deltalgt(190-685)). Moreover, mucus production was significantly greater in both
      wild-type-infected and Deltalgt(190-685)-infected organ cultures. Both mutants
      were significantly attenuated compared with the wild-type strain in a mouse model
      of strangles, although 2 of 30 mice infected with the Deltalgt(190-685) mutant
      did still exhibit signs of disease. In contrast, only the DeltaprtM(138-213)
      mutant was significantly attenuated in a pony infection study, with 0 of 5
      infected ponies exhibiting pathological signs of strangles compared with 4 of 4
      infected with the wild-type and 3 of 5 infected with the Deltalgt(190-685)
      mutant. We believe that this is the first study to evaluate the contribution of
      lipoproteins to the virulence of a gram-positive pathogen in its natural host.
      These data suggest that the PrtM lipoprotein is a potential vaccine candidate,
      and further investigation of its activity and its substrate(s) are warranted.

PMID- 17015456
TI  - NikR mediates nickel-responsive transcriptional repression of the Helicobacter
      pylori outer membrane proteins FecA3 (HP1400) and FrpB4 (HP1512).
AB  - The transition metal nickel plays an important role in gastric colonization and
      persistence of the important human pathogen Helicobacter pylori, as it is the
      cofactor of the abundantly produced acid resistance factor urease. Nickel uptake
      through the inner membrane is mediated by the NixA protein, and the expression of
      NixA is controlled by the NikR regulatory protein. Here we report that NikR also
      controls the nickel-responsive expression of the FecA3 (HP1400) and FrpB4
      (HP1512) outer membrane proteins (OMPs), as well as the nickel-responsive
      expression of an ExbB-ExbD-TonB system, which may function in energization of
      outer membrane transport. Transcription and expression of the frpB4 and fecA3
      genes were repressed by nickel in wild-type H. pylori 26695, but they were
      independent of nickel and derepressed in an isogenic nikR mutant. Both the frpB4
      and fecA3 genes were transcribed from a promoter directly upstream of their start
      codon. Regulation by NikR was mediated via nickel-dependent binding to specific
      operators overlapping either the +1 or -10 sequence in the frpB4 and fecA3
      promoters, respectively, and these operators contained sequences resembling the
      proposed H. pylori NikR recognition sequence (TATWATT-N(11)-AATWATA).
      Transcription of the HP1339-1340-1341 operon encoding the ExbB2-ExbD2-TonB2
      complex was also regulated by nickel and NikR, but not by Fur and iron. In
      conclusion, H. pylori NikR controls nickel-responsive expression of the HP1400
      (FecA3) and HP1512 (FrpB4) OMPs. We hypothesize that these two NikR-regulated
      OMPs may participate in the uptake of complexed nickel ions and that this process
      is energized by the NikR-regulated ExbB2-ExbD2-TonB2 system, another example of
      the specific adaptation of H. pylori to the gastric lifestyle.

PMID- 17015457
TI  - The translocated Salmonella effector proteins SseF and SseG interact and are
      required to establish an intracellular replication niche.
AB  - The facultative intracellular pathogen Salmonella enterica causes a variety of
      diseases, including gastroenteritis and typhoid fever. Inside epithelial cells,
      Salmonella replicates in vacuoles, which localize in the perinuclear area in
      close proximity to the Golgi apparatus. Among the effector proteins translocated
      by the Salmonella pathogenicity island 2-encoded type III secretion system, SifA
      and SseG have been shown necessary but not sufficient to ensure the intracellular
      positioning of Salmonella vacuoles. Hence, we have investigated the involvement
      of other secreted effector proteins in this process. Here we show that SseF
      interacts functionally and physically with SseG but not SifA and is also required
      for the perinuclear localization of Salmonella vacuoles. The observations show
      that the intracellular positioning of Salmonella vacuoles is a complex phenomenon
      resulting from the combined action of several effector proteins.

PMID- 17015458
TI  - Chlamydial protease-like activity factor induces protective immunity against
      genital chlamydial infection in transgenic mice that express the human HLA-DR4
      allele.
AB  - There is no licensed vaccine available against Chlamydia trachomatis, the leading
      cause of bacterial sexually transmitted disease. We have found that intranasal
      immunization with recombinant chlamydial protease-like activity factor (CPAF)
      induces CD4(+) T-cell- and gamma interferon (IFN-gamma)-dependent protective
      immunity against murine genital chlamydial infection, thus making CPAF a viable
      vaccine candidate for further characterization. HLA-DR4 is the predominant allele
      involved in chlamydial antigen presentation to CD4(+) T cells in humans. We used
      engineered mice that lack endogenous major histocompatibility complex class II
      (MHC-II) alleles but express a human HLA allele (HLA-DR4 transgenic [tg] mice) to
      examine primary immune and CPAF-mediated responses against genital Chlamydia
      muridarum challenge. Upon primary bacterial exposure, HLA-DR4 tg mice developed
      Chlamydia-specific IFN-gamma and antibody production and resolved the infection
      within 30 days, similar to challenged conventional C57BL/6 animals. Moreover, C.
      muridarum-challenged HLA-DR4 tg mice exhibited CPAF-specific antibody and IFN
      gamma production. Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg
      animals exhibited robust CPAF-specific IFN-gamma production and elevated titers
      of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of
      IgG2b and IgG1 antibodies. HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus
      IL-12 resolved the primary genital chlamydial infection significantly earlier
      than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient
      mice displayed minimal antigen-specific immune responses and failed to resolve
      the infection even at 30 days postchallenge. Together, these results demonstrate
      the importance of human HLA-DR4 molecules in the recognition and presentation of
      CPAF epitopes, leading to the generation of protective antichlamydial immunity
      and making these mice a valuable model for mapping HLA-DR4-restricted chlamydial
      epitopes.

PMID- 17015459
TI  - Identification of potential virulence determinants by Himar1 transposition of
      infectious Borrelia burgdorferi B31.
AB  - Lyme disease Borrelia organisms are highly invasive spirochetes that alternate
      between vertebrate and arthropod hosts and that establish chronic infections and
      elicit inflammatory reactions in mammals. Although progress has been made in the
      targeted mutagenesis of individual genes in infectious Borrelia burgdorferi, the
      roles of the vast majority of gene products in pathogenesis remain unresolved. In
      this study, we examined the feasibility of using transposon mutagenesis to
      identify infectivity-related factors in B. burgdorferi. The transformable,
      infectious strain 5A18 NP1 was transformed with the spirochete-adapted Himar1
      transposon delivery vector pMarGent to create a small library of 33 insertion
      mutants. Single mouse inoculations followed by culture of four tissue sites and
      serology were used to screen the mutants for infectivity phenotypes. Mutants that
      appeared attenuated (culture positive at some sites) or noninfectious (negative
      at all sites) and contained the virulence-associated plasmids lp25 and lp28-1
      were examined in more extensive animal studies. Three of these mutants (including
      those with insertions in the putative fliG-1-encoded flagellar motor switch
      protein and the guaB-encoded IMP dehydrogenase) were noninfectious, whereas four
      clones appeared to exhibit reduced infectivity. Serological reactivity in VlsE
      enzyme-linked immunosorbent assays correlated with the assignment of mutants to
      the noninfectious or attenuated-infectivity groups. The results of this study
      indicate that random transposon mutagenesis of infectious B. burgdorferi is
      feasible and will be of value in studying the pathogenesis of Lyme disease
      Borrelia.

PMID- 17015460
TI  - Limited cross-reactivity among domains of the Plasmodium falciparum clone 3D7
      erythrocyte membrane protein 1 family.
AB  - The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1
      (PfEMP1) family is responsible for antigenic variation and sequestration of
      infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1
      variants of P. falciparum clone 3D7 into groups A and B/A (category A) and groups
      B, B/C, and C (category non-A). Expression of category A molecules is associated
      with severe malaria, and that of category non-A molecules is associated with
      uncomplicated malaria and asymptomatic infection. Here we assessed cross
      reactivity among 60 different recombinant PfEMP1 domains derived from clone 3D7
      by using a competition enzyme-linked immunosorbent assay and a pool of plasma
      from 63 malaria-exposed Tanzanian individuals. We conclude that naturally
      acquired antibodies are largely directed toward epitopes varying between
      different domains with a few, mainly category A, domains sharing cross-reactive
      antibody epitopes. Identification of groups of serological cross-reacting
      molecules is pivotal for the development of vaccines based on PfEMP1.

PMID- 17015461
TI  - 2,3-butanediol synthesis and the emergence of the Vibrio cholerae El Tor biotype.
AB  - Vibrio cholerae is an aquatic bacterium that causes the severe diarrheal disease
      cholera. V. cholerae strains of the O1 serogroup exist as two biotypes, classical
      and El Tor. Toxigenic strains of the El Tor biotype emerged to cause the seventh
      pandemic of cholera in 1961 and subsequently displaced strains of the classical
      biotype both in the environment and as a cause of cholera within a decade. The
      factors that drove emergence of the El Tor biotype and the displacement of the
      classical biotype are unknown. Here, we show a unique difference in carbohydrate
      metabolism between these two biotypes. When grown with added carbohydrates,
      classical biotype strains generated a sharp decrease in medium pH, resulting in
      loss of viability. However, growth of El Tor biotype strain N16961 was enhanced
      due to its ability to produce 2,3-butanediol, a neutral fermentation end product,
      and suppress the accumulation of organic acids. An N16961 mutant (SSY01)
      defective in 2,3-butanediol synthesis showed the same defect in growth that
      classical biotype strains show in media rich in carbohydrates. Importantly, the
      SSY01 mutant was attenuated in its ability to colonize the intestines of infant
      mice, suggesting that host carbohydrates may be available to V. cholerae within
      the intestinal environment. Similarly, the SSY01 mutant failed to develop
      biofilms when utilizing N-acetyl-D-glucosamine as a carbon source. Because growth
      on N-acetyl-D-glucosamine likely reflects the ability of a strain to grow on
      chitin in certain aquatic environments, we conclude that the strains of classical
      biotype are likely defective compared to those of El Tor in growth in any
      environmental niche that is rich in chitin and/or other metabolizable
      carbohydrates. We propose that the ability to metabolize sugars without
      production of acid by-products might account for the improved evolutionary
      fitness of the V. cholerae El Tor biotype compared to that of the classical
      biotype both as a global cause of cholera and as an environmental organism.

PMID- 17015462
TI  - Pseudomonas aeruginosa LecB is involved in pilus biogenesis and protease IV
      activity but not in adhesion to respiratory mucins.
AB  - Pseudomonas aeruginosa expresses two lectins which are implicated in adhesion and
      biofilm formation. In this study, we demonstrate that P. aeruginosa LecB is
      involved in pilus biogenesis and proteolytic activity. Moreover, neither lectin
      was involved in adhesion to human tracheobronchial mucin. We infer that some of
      the ascribed functions are secondary effects on other systems rather than effects
      of the lectins themselves.

PMID- 17015463
TI  - Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome
      duplication.
AB  - Nucleophosmin (NPM)/B23 has been implicated in the regulation of centrosome
      duplication. NPM/B23 localizes between two centrioles in the unduplicated
      centrosome. Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2
      (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from
      centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes.
      It has been shown that Thr(199) phosphorylation of NPM/B23 is critical for the
      physical separation of the paired centrioles, an initial event of the centrosome
      duplication process. Here, we identified ROCK II kinase, an effector of Rho small
      GTPase, as a protein that localizes to centrosomes and physically interacts with
      NPM/B23. Expression of the constitutively active form of ROCK II promotes
      centrosome duplication, while down-regulation of ROCK II expression results in
      the suppression of centrosome duplication, especially delaying the initiation of
      centrosome duplication during the cell cycle. Moreover, ROCK II regulates
      centrosome duplication in its kinase and centrosome localization activity
      dependent manner. We further found that ROCK II kinase activity is significantly
      enhanced by binding to NPM/B23 and that NPM/B23 acquires a higher binding
      affinity to ROCK II upon phosphorylation on Thr(199). Moreover, physical
      interaction between ROCK II and NPM/B23 in vivo occurs in association with
      CDK2/cyclin E activation and the emergence of Thr(199)-phosphorylated NPM/B23.
      All these findings point to ROCK II as the effector of the CDK2/cyclin E-NPM/B23
      pathway in the regulation of centrosome duplication.

PMID- 17015464
TI  - The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via
      recruiting a p160/SRC coactivator.
AB  - Hormones provide generalized signals that are interpreted in a specific spatial
      and temporal manner by a developing or reproducing multicellular organism. The
      ability to respond to hormones is determined by the competence of a cell or a
      tissue. The betaFtz-F1 orphan nuclear receptor acts as a competence factor for
      the steroid hormone 20-hydroxyecdysone (20E) in Drosophila melanogaster
      metamorphosis and mosquito reproduction. The molecular nature of the betaFtz-F1
      action remains unclear. We report that the protein-protein interaction between
      betaFtz-F1 and a p160/SRC coactivator of the ecdysone receptor, FISC, is crucial
      for the stage-specific expression of the 20E effector genes during mosquito
      reproduction. This interaction dramatically increases recruitment of FISC to the
      functional ecdysone receptor in a 20E-dependent manner. The presence of betaFtz
      F1 facilitates loading of FISC and the ecdysone receptor on the target promoters,
      leading to enhanced local histone H4 acetylation and robust activation of the
      target genes. Thus, our results reveal the molecular basis of competence for the
      stage-specific 20E response.

PMID- 17015465
TI  - The LRS and SIN domains: two structurally equivalent but functionally distinct
      nucleosomal surfaces required for transcriptional silencing.
AB  - Genetic experiments have identified two structurally similar nucleosomal domains,
      SIN and LRS, required for transcriptional repression at genes regulated by the
      SWI/SNF chromatin remodeling complex or for heterochromatic gene silencing,
      respectively. Each of these domains consists of histone H3 and H4 L1 and L2 loops
      that form a DNA-binding surface at either superhelical location (SHL) +/-2.5
      (LRS) or SHL +/-0.5 (SIN). Here we show that alterations in the LRS domain do not
      result in Sin(-) phenotypes, nor does disruption of the SIN domain lead to loss
      of ribosomal DNA heterochromatic gene silencing (Lrs(-) phenotype). Furthermore,
      whereas disruption of the SIN domain eliminates intramolecular folding of
      nucleosomal arrays in vitro, alterations in the LRS domain have no effect on
      chromatin folding in vitro. In contrast to these dissimilarities, we find that
      the SIN and LRS domains are both required for recruitment of Sir2p and Sir4p to
      telomeric and silent mating type loci, suggesting that both surfaces can
      contribute to heterochromatin formation. Our study shows that structurally
      similar nucleosomal surfaces provide distinct functionalities in vivo and in
      vitro.

PMID- 17015466
TI  - Phosphoinositide 3-kinase activation in late G1 is required for c-Myc
      stabilization and S phase entry.
AB  - Phosphoinositide 3-kinase (PI3K) is one of the early-signaling molecules induced
      by growth factor (GF) receptor stimulation that are necessary for cell growth and
      cell cycle entry. PI3K activation occurs at two distinct time points during G(1)
      phase. The first peak is observed immediately following GF addition and the
      second in late G(1), before S phase entry. This second activity peak is essential
      for transition from G(1) to S phase; nonetheless, the mechanism by which this
      peak is induced and regulates S phase entry is poorly understood. Here, we show
      that activation of Ras and Tyr kinases is required for late-G(1) PI3K activation.
      Inhibition of late-G(1) PI3K activity results in low c-Myc and cyclin A
      expression, impaired Cdk2 activity, and reduced loading of MCM2 (minichromosome
      maintenance protein) onto chromatin. The primary consequence of inhibiting late
      G(1) PI3K was c-Myc destabilization, as conditional activation of c-Myc in
      advanced G(1) as well as expression of a stable c-Myc mutant rescued all of these
      defects, restoring S phase entry. These results show that Tyr kinases and Ras
      cooperate to induce the second PI3K activity peak in G(1), which mediates
      initiation of DNA synthesis by inducing c-Myc stabilization.

PMID- 17015467
TI  - Long-term memory deficits in Pavlovian fear conditioning in Ca2+/calmodulin
      kinase kinase alpha-deficient mice.
AB  - Signaling by the Ca(2+)/calmodulin kinase (CaMK) cascade has been implicated in
      neuronal gene transcription, synaptic plasticity, and long-term memory
      consolidation. The CaM kinase kinase alpha (CaMKKalpha) isoform is an upstream
      component of the CaMK cascade whose function in different behavioral and learning
      and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKalpha
      mutants exhibited normal long-term spatial memory formation and cued fear
      conditioning but showed deficits in context fear during both conditioning and
      long-term follow-up testing. They also exhibited impaired activation of the
      downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic
      AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike
      CaMKIV/Gr-deficient mice, the CaMKKalpha mutants exhibited normal long-term
      potentiation and normal levels of anxiety-like behavior. These results
      demonstrate a selective role for CaMKKalpha in contextual fear memory and suggest
      that different combinations of upstream and downstream components of the CaMK
      cascade may serve distinct physiological functions.

PMID- 17015468
TI  - Ca2+/calmodulin kinase kinase alpha is dispensable for brain development but is
      required for distinct memories in male, though not in female, mice.
AB  - In neurons, the Ca(2+)/calmodulin (CaM) kinase cascade transduces Ca(2+)
      signaling into gene transcription. The CaM kinase cascade is known to be
      important for brain development as well as memory formation in adult brain,
      although the functions of some cascade members remain unknown. Here we have
      generated null and hypomorphic mutants to study the physiological role of CaM
      kinase kinase alpha (CaMKKalpha), which phosphorylates and activates both CaM
      kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that
      CaMKKalpha is dispensable for brain development and long-term potentiation in
      adult hippocampal CA1 synapses. We find that CaMKKalpha is required for
      hippocampus-dependent contextual fear memory, but not spatial memory, formation.
      Surprisingly, CaMKKalpha is important for contextual fear memory formation in
      males but not in females. We show that in male mice, contextual fear conditioning
      induces up-regulation of hippocampal mRNA expression of brain-derived
      neurotrophic factor (BDNF) in a way that requires CaMKKalpha, while in female
      mice, contextual fear conditioning induces down-regulation of hippocampal BDNF
      mRNA expression that does not require CaMKKalpha. Additionally, we demonstrate
      sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B
      mRNA expression that does not require CaMKKalpha. Thus, we show that CaMKKalpha
      has a specific complex role in memory formation in males.

PMID- 17015469
TI  - Transcription domain-associated repair in human cells.
AB  - Nucleotide excision repair (NER), which is arguably the most versatile DNA repair
      system, is strongly attenuated in human cells of the monocytic lineage when they
      differentiate into macrophages. Within active genes, however, both DNA strands
      continue to be proficiently repaired. The proficient repair of the nontranscribed
      strand cannot be explained by the dedicated subpathway of transcription-coupled
      repair (TCR), which is targeted to the transcribed strand in expressed genes. We
      now report that the previously termed differentiation-associated repair (DAR)
      depends upon transcription, but not simply upon RNA polymerase II (RNAPII)
      encountering a lesion: proficient repair of both DNA strands can occur in a part
      of a gene that the polymerase never reaches, and even if the translocation of
      RNAPII is blocked with transcription inhibitors. This suggests that DAR may be a
      subset of global NER, restricted to the subnuclear compartments or chromatin
      domains within which transcription occurs. Downregulation of selected NER genes
      with small interfering RNA has confirmed that DAR relies upon the same genes as
      global genome repair, rather than upon TCR-specific genes. Our findings support
      the general view that the genomic domains within which transcription is active
      are more accessible than the bulk of the genome to the recognition and repair of
      lesions through the global pathway and that TCR is superimposed upon that pathway
      of NER.

PMID- 17015470
TI  - GIPC is recruited by APPL to peripheral TrkA endosomes and regulates TrkA
      trafficking and signaling.
AB  - GIPC is a PDZ protein located on peripheral endosomes that binds to the
      juxtamembrane region of the TrkA nerve growth factor (NGF) receptor and has been
      implicated in NGF signaling. We establish here that endogenous GIPC binds to the
      C terminus of APPL, a Rab5 binding protein, which is a marker for signaling
      endosomes. When PC12(615) cells are treated with either NGF or antibody agonists
      to activate TrkA, GIPC and APPL translocate from the cytoplasm and bind to
      incoming, endocytic vesicles carrying TrkA concentrated at the tips of the cell
      processes. GIPC, but not APPL, dissociates from these peripheral endosomes prior
      to or during their trafficking from the cell periphery to the juxtanuclear
      region, where they acquire EEA1. GIPC's interaction with APPL is essential for
      recruitment of GIPC to peripheral endosomes and for TrkA signaling, because a
      GIPC PDZ domain mutant that cannot bind APPL or APPL knockdown with small
      interfering RNA inhibits NGF-induced GIPC recruitment, mitogen-activated protein
      kinase activation, and neurite outgrowth. GIPC is also required for efficient
      endocytosis and trafficking of TrkA because depletion of GIPC slows down
      endocytosis and trafficking of TrkA and APPL to the early EEA1 endosomes in the
      juxtanuclear region. We conclude that GIPC, following its recruitment to TrkA by
      APPL, plays a key role in TrkA trafficking and signaling from endosomes.

PMID- 17015471
TI  - Regulation of ISW2 by concerted action of histone H4 tail and extranucleosomal
      DNA.
AB  - The stable contact of ISW2 with nucleosomal DNA approximately 20 bp from the dyad
      was shown by DNA footprinting and photoaffinity labeling using recombinant
      histone octamers to require the histone H4 N-terminal tail. Efficient ISW2
      remodeling also required the H4 N-terminal tail, although the lack of the H4 tail
      can be mostly compensated for by increasing the incubation time or concentration
      of ISW2. Similarly, the length of extranucleosomal DNA affected the stable
      contact of ISW2 with this same internal nucleosomal site, with the optimal length
      being 70 to 85 bp. These data indicate the histone H4 tail, in concert with a
      favorable length of extranucleosomal DNA, recruits and properly orients ISW2 onto
      the nucleosome for efficient nucleosome remodeling. One consequence of this
      property of ISW2 is likely its previously observed nucleosome spacing activity.

PMID- 17015472
TI  - Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent
      apoptosis.
AB  - Apoptosis, induced by a number of death stimuli, is associated with a
      fragmentation of the mitochondrial network. These morphological changes in
      mitochondria have been shown to require proteins, such as Drp1 or hFis1, which
      are involved in regulating the fission of mitochondria. However, the precise role
      of mitochondrial fission during apoptosis remains elusive. Here we report that
      inhibiting the fission machinery in Bax/Bak-mediated apoptosis, by down
      regulating of Drp1 or hFis1, prevents the fragmentation of the mitochondrial
      network and partially inhibits the release of cytochrome c from the mitochondria
      but fails to block the efflux of Smac/DIABLO. In addition, preventing
      mitochondrial fragmentation does not inhibit cell death induced by Bax/Bak
      dependent death stimuli, in contrast to the effects of Bcl-xL or caspase
      inhibition. Therefore, the fission of mitochondria is a dispensable event in
      Bax/Bak-dependent apoptosis.

PMID- 17015473
TI  - AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation
      of AML1/RUNX1 by the anaphase-promoting complex.
AB  - AML1 (RUNX1) regulates hematopoiesis, angiogenesis, muscle function, and
      neurogenesis. Previous studies have shown that phosphorylation of AML1,
      particularly at serines 276 and 303, affects its transcriptional activation.
      Here, we report that phosphorylation of AML1 serines 276 and 303 can be blocked
      in vivo by inhibitors of the cyclin-dependent kinases (CDKs) Cdk1 and Cdk2.
      Furthermore, these residues can be phosphorylated in vitro by purified
      Cdk1/cyclin B and Cdk2/cyclin A. Mutant AML1 protein which cannot be
      phosphorylated at these sites (AML1-4A) is more stable than wild-type AML1. AML
      4A is resistant to degradation mediated by Cdc20, one of the substrate-targeting
      subunits of the anaphase-promoting complex (APC). However, Cdh1, another
      targeting subunit used by the APC, can mediate the degradation of AML1-4A. A
      phospho-mimic protein, AML1-4D, can be targeted by Cdc20 or Cdh1. These
      observations suggest that both Cdc20 and Cdh1 can target AML1 for degradation by
      the APC but that AML1 phosphorylation may affect degradation mediated by Cdc20
      APC to a greater degree.

PMID- 17015474
TI  - Differentiation-induced cleavage of Cutl1/CDP generates a novel dominant-negative
      isoform that regulates mammary gene expression.
AB  - Cutl1/CCAAT displacement protein (CDP) is a transcriptional repressor of mouse
      mammary tumor virus (MMTV), a betaretrovirus that is a paradigm for mammary
      specific gene regulation. Virgin mammary glands have high levels of full-length
      CDP (200 kDa) that binds to negative regulatory elements (NREs) to repress MMTV
      transcription. During late pregnancy, full-length CDP levels decline, and a 150
      kDa form of CDP (CDP150) appears concomitantly with a decline in DNA-binding
      activity for the MMTV NREs and an increase in viral transcripts. Developmental
      regulation of CDP was recapitulated in the normal mammary epithelial line, SCp2.
      Western blotting of tissue and SCp2 nuclear extracts confirmed that CDP150 lacks
      the C terminus. Transfection of tagged full-length and mutant cDNAs into SCp2
      cells and use of a cysteine protease inhibitor demonstrated that CDP is
      proteolytically processed within the homeodomain to remove the C terminus during
      differentiation. Mixing of virgin and lactating mammary extracts or transfection
      of mutant CDP cDNAs missing the homeodomain into cells containing full-length CDP
      also abrogated NRE binding. Loss of DNA binding correlated with increased
      expression of MMTV and other mammary-specific genes, indicating that CDP150 is a
      developmentally induced dominant-negative protein. Thus, a novel
      posttranslational process controls Cutl1/CDP activity and gene expression in the
      mammary gland.

PMID- 17015475
TI  - Two isoforms of Drosophila TRF2 are involved in embryonic development, premeiotic
      chromatin condensation, and proper differentiation of germ cells of both sexes.
AB  - The Drosophila TATA box-binding protein (TBP)-related factor 2 (TRF2 or TLF) was
      shown to control a subset of genes different from that controlled by TBP. Here,
      we have investigated the structure and functions of the trf2 gene. We demonstrate
      that it encodes two protein isoforms: the previously described 75-kDa TRF2 and a
      newly identified 175-kDa version in which the same sequence is preceded by a long
      N-terminal domain with coiled-coil motifs. Chromatography of Drosophila embryo
      extracts revealed that the long TRF2 is part of a multiprotein complex also
      containing ISWI. Both TRF2 forms are detected at the same sites on polytene
      chromosomes and have the same expression patterns, suggesting that they fulfill
      similar functions. A study of the manifestations of the trf2 mutation suggests an
      essential role of TRF2 during embryonic Drosophila development. The trf2 gene is
      strongly expressed in germ line cells of adult flies. High levels of TRF2 are
      found in nuclei of primary spermatocytes and trophocytes with intense
      transcription. In ovaries, TRF2 is present both in actively transcribing nurse
      cells and in the transcriptionally inactive oocyte nuclei. Moreover, TRF2 is
      essential for premeiotic chromatin condensation and proper differentiation of
      germ cells of both sexes.

PMID- 17015476
TI  - Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein
      phosphatase 2A circuit.
AB  - In higher eukaryotic organisms, the checkpoint kinase 1 (Chk1) contributes
      essential functions to both cell cycle and checkpoint control. Chk1 executes
      these functions, in part, by targeting the Cdc25A protein phosphatase for
      ubiquitin-mediated proteolysis. In response to genotoxic stress, Chk1 is
      phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia
      related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine
      residues is used as an indicator of Chk1 activation in vivo. Here, we report that
      inhibition of Chk1 kinase activity paradoxically leads to the accumulation of
      S317- and S345-phosphorylated Chk1 in vivo and that ATR catalyzes Chk1
      phosphorylation under these conditions. We demonstrate that Chk1 phosphorylation
      by ATR is antagonized by protein phosphatase 2A (PP2A). Importantly,
      dephosphorylation of Chk1 by PP2A is regulated, in part, by the kinase activity
      of Chk1. We propose that the ATR-Chk1-PP2A regulatory circuit functions to keep
      Chk1 in a low-activity state during an unperturbed cell division cycle but at the
      same time keeps Chk1 primed to respond rapidly in the event that cells encounter
      genotoxic stress.

PMID- 17015477
TI  - Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression
      and inhibits growth and invasion of prostate cancer.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) might not be
      permissive to ligand activation in prostate cancer cells. Association of
      PPARgamma with repressing factors or posttranslational modifications in PPARgamma
      protein could explain the lack of effect of PPARgamma ligands in a recent
      randomized clinical trial. Using cells and prostate cancer xenograft mouse
      models, we demonstrate in this study that a combination treatment using the
      PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic
      acid is more efficient at inhibiting prostate tumor growth than each individual
      therapy. We show that the combination treatment impairs the bone-invasive
      potential of prostate cancer cells in mice. In addition, we demonstrate that
      expression of E-cadherin, a protein involved in the control of cell migration and
      invasion, is highly up-regulated in the presence of valproic acid and
      pioglitazone. We show that E-cadherin expression responds only to the combination
      treatment and not to single PPARgamma agonists, defining a new class of PPARgamma
      target genes. These results open up new therapeutic perspectives in the treatment
      of prostate cancer.

PMID- 17015478
TI  - DNA methyltransferase 1 knockdown activates a replication stress checkpoint.
AB  - DNA methyltransferase 1 (DNMT1) is an important component of the epigenetic
      machinery and is responsible for copying DNA methylation patterns during cell
      division. Coordination of DNA methylation and DNA replication is critical for
      maintaining epigenetic programming. Knockdown of DNMT1 leads to inhibition of DNA
      replication, but the mechanism has been unclear. Here we show that depletion of
      DNMT1 with either antisense or small interfering RNA (siRNA) specific to DNMT1
      activates a cascade of genotoxic stress checkpoint proteins, resulting in
      phosphorylation of checkpoint kinases 1 and 2 (Chk1 and -2), gammaH2AX focus
      formation, and cell division control protein 25a (CDC25a) degradation, in an
      ataxia telangiectasia mutated-Rad3-related (ATR)-dependent manner. siRNA
      knockdown of ATR blocks the response to DNMT1 depletion; DNA synthesis continues
      in the absence of DNMT1, resulting in global hypomethylation. Similarly, the
      response to DNMT1 knockdown is significantly attenuated in human mutant ATR
      fibroblast cells from a Seckel syndrome patient. This response is sensitive to
      DNMT1 depletion, independent of the catalytic domain of DNMT1, as indicated by
      abolition of the response with ectopic expression of either DNMT1 or DNMT1 with
      the catalytic domain deleted. There is no response to short-term treatment with 5
      aza-deoxycytidine (5-aza-CdR), which causes demethylation by trapping DNMT1 in 5
      aza-CdR-containing DNA but does not cause disappearance of DNMT1 from the
      nucleus. Our data are consistent with the hypothesis that removal of DNMT1 from
      replication forks is the trigger for this response.

PMID- 17015479
TI  - Displacement of histones at promoters of Saccharomyces cerevisiae heat shock
      genes is differentially associated with histone H3 acetylation.
AB  - Chromatin remodeling at promoters of activated genes spans from mild histone
      modifications to outright displacement of nucleosomes in trans. Factors affecting
      these events are not always clear. Our results indicate that histone H3
      acetylation associated with histone displacement differs drastically even between
      promoters of such closely related heat shock genes as HSP12, SSA4, and HSP82. The
      HSP12 promoter, with the highest level of histone displacement, showed the
      highest level of H3 acetylation, while the SSA4 promoter, with a lower histone
      displacement, showed only modest H3 acetylation. Moreover, for the HSP12
      promoter, the level of acetylated H3 is temporarily increased prior to nucleosome
      departure. Individual promoters in strains expressing truncated versions of heat
      shock factor (HSF) showed that deletion of either one of two activating regions
      in HSF led to the diminished histone displacement and correspondingly lower H3
      acetylation. The deletion of both regions simultaneously severely decreased
      histone displacement for all promoters tested, showing the dependence of these
      processes on HSF. The level of histone H3 acetylation at individual promoters in
      strains expressing truncated HSF also correlated with the extent of histone
      displacement. The beginning of chromatin remodeling coincides with the polymerase
      II loading on heat shock gene promoters and is regulated either by HSF binding or
      activation of preloaded HSF.

PMID- 17015480
TI  - TReP-132 is a novel progesterone receptor coactivator required for the inhibition
      of breast cancer cell growth and enhancement of differentiation by progesterone.
AB  - The sex steroid progesterone is essential for the proliferation and
      differentiation of the mammary gland epithelium during pregnancy. In relation to
      this, in vitro studies using breast carcinoma T47D cells have demonstrated a
      biphasic progesterone response, consisting of an initial proliferative burst
      followed by a sustained growth arrest. However, the transcriptional factors
      acting with the progesterone receptor (PR) to mediate the progesterone effects on
      mammary cell growth and differentiation remain to be determined. Recently, it has
      been demonstrated that the transcriptional regulating protein of 132 kDa (TReP
      132), initially identified as a regulator of steroidogenesis, is also a cell
      growth suppressor. Similar to progesterone-bound PR, TReP-132 acts by inducing
      the gene expression of the G1 cyclin-dependent kinase inhibitors p21WAF1/Cip1
      (p21) and p27Kip1 (p27). The putative interaction between TReP-132 and
      progesterone pathways in mammary cells was therefore analyzed in the present
      study. Our results show that TReP-132 interacts in vitro and in T47D cells with
      progesterone-activated PR. TReP-132 synergizes with progesterone-bound PR to
      trans activate the p21 and p27 gene promoters at proximal Sp1-binding sites.
      Moreover, TReP-132 overexpression and knockdown, respectively, increased or
      prevented the induction of p21 and p27 gene expression by progesterone. As a
      consequence, TReP-132 knockdown also resulted in the loss of the inhibitory
      effects of progesterone on pRB phosphorylation, G1/S cell cycle progression, and
      cell proliferation. Furthermore, the knockdown of TReP-132 expression also
      prevented the induction of both early and terminal markers of breast cell
      differentiation which had been previously identified as progesterone target
      genes. As well, the progesterone-induced accumulation of lipid vacuoles was
      inhibited in the TReP-132-depleted cells. Finally, TReP-132 gene expression
      levels increased following progesterone treatment, indicating the existence of a
      positive auto-regulatory loop between PR and TReP-132. Taken together, these data
      identify TReP-132 as a coactivator of PR mediating the growth-inhibitory and
      differentiation effects of progesterone on breast cancer cells.

PMID- 17015481
TI  - An artificially constructed de novo human chromosome behaves almost identically
      to its natural counterpart during metaphase and anaphase in living cells.
AB  - Human artificial chromosomes (HACs) are promising reagents for the analysis of
      chromosome function. While HACs are maintained stably, the segregation mechanisms
      of HACs have not been investigated in detail. To analyze HACs in living cells, we
      integrated 256 copies of the Lac operator into a precursor yeast artificial
      chromosome (YAC) containing alpha-satellite DNA and generated green fluorescent
      protein (GFP)-tagged HACs in HT1080 cells expressing a GFP-Lac repressor fusion
      protein. Time-lapse analyses of GFP-HACs and host centromeres in living mitotic
      cells indicated that the HAC was properly aligned at the spindle midzone and that
      sister chromatids of the HAC separated with the same timing as host chromosomes
      and moved to the spindle poles with mobility similar to that of the host
      centromeres. These results indicate that a HAC composed of a multimer of input
      alpha-satellite YACs retains most of the functions of the centromeres on natural
      chromosomes. The only difference between the HAC and the host chromosome was that
      the HAC oscillated more frequently, at higher velocity, across the spindle
      midzone during metaphase. However, this provides important evidence that an
      individual HAC has the capacity to maintain tensional balance in the pole-to-pole
      direction, thereby stabilizing its position around the spindle midzone.

PMID- 17015482
TI  - UV-B radiation induces epithelial tumors in mice lacking DNA polymerase eta and
      mesenchymal tumors in mice deficient for DNA polymerase iota.
AB  - DNA polymerase eta (Pol eta) is the product of the Polh gene, which is
      responsible for the group variant of xeroderma pigmentosum, a rare inherited
      recessive disease which is characterized by susceptibility to sunlight-induced
      skin cancer. We recently reported in a study of Polh mutant mice that Pol eta is
      involved in the somatic hypermutation of immunoglobulin genes, but the cancer
      predisposition of Polh-/- mice has not been examined until very recently. Another
      translesion synthesis polymerase, Pol iota, a Pol eta paralog encoded by the Poli
      gene, is naturally deficient in the 129 mouse strain, and the function of Pol
      iota is enigmatic. Here, we generated Polh Poli double-deficient mice and
      compared the tumor susceptibility of them with Polh- or Poli-deficient animals
      under the same genetic background. While Pol iota deficiency does not influence
      the UV sensitivity of mouse fibroblasts irrespective of Polh genotype, Polh Poli
      double-deficient mice show slightly earlier onset of skin tumor formation.
      Intriguingly, histological diagnosis after chronic treatment with UV light
      reveals that Pol iota deficiency leads to the formation of mesenchymal tumors,
      such as sarcomas, that are not observed in Polh(-/-) mice. These results suggest
      the involvement of the Pol eta and Pol iota proteins in UV-induced skin
      carcinogenesis.

PMID- 17015484
TI  - Role of Na+ and K+ in enzyme function.
AB  - Metal complexation is a key mediator or modifier of enzyme structure and
      function. In addition to divalent and polyvalent metals, group IA metals Na+ and
      K+ play important and specific roles that assist function of biological
      macromolecules. We examine the diversity of monovalent cation (M+)-activated
      enzymes by first comparing coordination in small molecules followed by a
      discussion of theoretical and practical aspects. Select examples of enzymes that
      utilize M+ as a cofactor (type I) or allosteric effector (type II) illustrate the
      structural basis of activation by Na+ and K+, along with unexpected connections
      with ion transporters. Kinetic expressions are derived for the analysis of type I
      and type II activation. In conclusion, we address evolutionary implications of
      Na+ binding in the trypsin-like proteases of vertebrate blood coagulation. From
      this analysis, M+ complexation has the potential to be an efficient regulator of
      enzyme catalysis and stability and offers novel strategies for protein
      engineering to improve enzyme function.

PMID- 17015483
TI  - Mutation in the Trapalpha/Ssr1 gene, encoding translocon-associated protein
      alpha, results in outflow tract morphogenetic defects.
AB  - Translocon-associated protein complex (TRAP) is thought to be required for
      efficient protein-specific translocation across the endoplasmic reticulum
      membrane. We created a mutation in the Trapalpha gene that leads to the synthesis
      of a truncated TRAPalpha protein fused to ShBle-beta-galactosidase. Analysis of
      Trapalpha cDNAs reveals that among three different messenger RNAs expressed in
      the mouse, one of them encodes a slightly larger protein that differs in its C
      terminal end. This mRNA, specific for skeletal muscle and heart, is only
      expressed after birth. Homozygous Trapalpha mutant pups die at birth, likely as a
      result of severe cardiac defects. Indeed, the septation of the proximal part of
      the outflow tract is absent, resulting in a double-outlet right ventricle.
      Studies of protein secretion in transfected embryonic fibroblasts reveal that the
      TRAP complex does not function properly in homozygous mutant cells and confirm,
      in vivo, the involvement of TRAP in substrate-specific translocation. Our results
      provide the first in vivo demonstration that a member of the TRAP complex plays a
      crucial role in mammalian heart development and suggest that TRAPalpha could be
      involved in translocation of factors necessary for maturation of endocardial
      cushions.

PMID- 17015485
TI  - Calcium signaling and exocytosis in adrenal chromaffin cells.
AB  - At a given cytosolic domain of a chromaffin cell, the rate and amplitude of the
      Ca2+ concentration ([Ca2+]c) depends on at least four efficient regulatory
      systems: 1) plasmalemmal calcium channels, 2) endoplasmic reticulum, 3)
      mitochondria, and 4) chromaffin vesicles. Different mammalian species express
      different levels of the L, N, P/Q, and R subtypes of high-voltage-activated
      calcium channels; in bovine and humans, P/Q channels predominate, whereas in
      felines and murine species, L-type channels predominate. The calcium channels in
      chromaffin cells are regulated by G proteins coupled to purinergic and opiate
      receptors, as well as by voltage and the local changes of [Ca2+]c. Chromaffin
      cells have been particularly useful in studying calcium channel current
      autoregulation by materials coreleased with catecholamines, such as ATP and
      opiates. Depending on the preparation (cultured cells, adrenal slices) and the
      stimulation pattern (action potentials, depolarizing pulses, high K+,
      acetylcholine), the role of each calcium channel in controlling catecholamine
      release can change drastically. Targeted aequorin and confocal microscopy shows
      that Ca2+ entry through calcium channels can refill the endoplasmic reticulum
      (ER) to nearly millimolar concentrations, and causes the release of Ca2+ (CICR).
      Depending on its degree of filling, the ER may act as a sink or source of Ca2+
      that modulates catecholamine release. Targeted aequorins with different Ca2+
      affinities show that mitochondria undergo surprisingly rapid millimolar Ca2+
      transients, upon stimulation of chromaffin cells with ACh, high K+, or caffeine.
      Physiological stimuli generate [Ca2+]c microdomains in which the local
      subplasmalemmal [Ca2+]c rises abruptly from 0.1 to approximately 50 microM,
      triggering CICR, mitochondrial Ca2+ uptake, and exocytosis at nearby secretory
      active sites. The fact that protonophores abolish mitochondrial Ca2+ uptake, and
      increase catecholamine release three- to fivefold, support the earlier
      observation. This increase is probably due to acceleration of vesicle transport
      from a reserve pool to a ready-release vesicle pool; this transport might be
      controlled by Ca2+ redistribution to the cytoskeleton, through CICR, and/or
      mitochondrial Ca2+ release. We propose that chromaffin cells have developed
      functional triads that are formed by calcium channels, the ER, and the
      mitochondria and locally control the [Ca2+]c that regulate the early and late
      steps of exocytosis.

PMID- 17015486
TI  - Endoplasmic reticulum stress signaling in disease.
AB  - The extracellular space is an environment hostile to unmodified polypeptides. For
      this reason, many eukaryotic proteins destined for exposure to this environment
      through secretion or display at the cell surface require maturation steps within
      a specialized organelle, the endoplasmic reticulum (ER). A complex homeostatic
      mechanism, known as the unfolded protein response (UPR), has evolved to link the
      load of newly synthesized proteins with the capacity of the ER to mature them. It
      has become apparent that dysfunction of the UPR plays an important role in some
      human diseases, especially those involving tissues dedicated to extracellular
      protein synthesis. Diabetes mellitus is an example of such a disease, since the
      demands for constantly varying levels of insulin synthesis make pancreatic beta
      cells dependent on efficient UPR signaling. Furthermore, recent discoveries in
      this field indicate that the importance of the UPR in diabetes is not restricted
      to the beta-cell but is also involved in peripheral insulin resistance. This
      review addresses aspects of the UPR currently understood to be involved in human
      disease, including their role in diabetes mellitus, atherosclerosis, and
      neoplasia.

PMID- 17015487
TI  - (Patho)physiological significance of the serum- and glucocorticoid-inducible
      kinase isoforms.
AB  - The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed
      and under genomic control by cell stress (including cell shrinkage) and hormones
      (including gluco- and mineralocorticoids). Similar to its isoforms SGK2 and SGK3,
      SGK1 is activated by insulin and growth factors via phosphatidylinositol 3-kinase
      and the 3-phosphoinositide-dependent kinase PDK1. SGKs activate ion channels
      (e.g., ENaC, TRPV5, ROMK, Kv1.3, KCNE1/KCNQ1, GluR1, GluR6), carriers (e.g.,
      NHE3, GLUT1, SGLT1, EAAT1-5), and the Na+-K+-ATPase. They regulate the activity
      of enzymes (e.g., glycogen synthase kinase-3, ubiquitin ligase Nedd4-2,
      phosphomannose mutase-2) and transcription factors (e.g., forkhead transcription
      factor FKHRL1, beta-catenin, nuclear factor kappaB). SGKs participate in the
      regulation of transport, hormone release, neuroexcitability, cell proliferation,
      and apoptosis. SGK1 contributes to Na+ retention and K+ elimination of the
      kidney, mineralocorticoid stimulation of salt appetite, glucocorticoid
      stimulation of intestinal Na+/H+ exchanger and nutrient transport, insulin
      dependent salt sensitivity of blood pressure and salt sensitivity of peripheral
      glucose uptake, memory consolidation, and cardiac repolarization. A common (
      approximately 5% prevalence) SGK1 gene variant is associated with increased blood
      pressure and body weight. SGK1 may thus contribute to metabolic syndrome. SGK1
      may further participate in tumor growth, neurodegeneration, fibrosing disease,
      and the sequelae of ischemia. SGK3 is required for adequate hair growth and
      maintenance of intestinal nutrient transport and influences locomotive behavior.
      In conclusion, the SGKs cover a wide variety of physiological functions and may
      play an active role in a multitude of pathophysiological conditions. There is
      little doubt that further targets will be identified that are modulated by the
      SGK isoforms and that further SGK-dependent in vivo physiological functions and
      pathophysiological conditions will be defined.

PMID- 17015488
TI  - Human multidrug resistance ABCB and ABCG transporters: participation in a
      chemoimmunity defense system.
AB  - In this review we give an overview of the physiological functions of a group of
      ATP binding cassette (ABC) transporter proteins, which were discovered, and still
      referred to, as multidrug resistance (MDR) transporters. Although they indeed
      play an important role in cancer drug resistance, their major physiological
      function is to provide general protection against hydrophobic xenobiotics. With a
      highly conserved structure, membrane topology, and mechanism of action, these
      essential transporters are preserved throughout all living systems, from bacteria
      to human. We describe the general structural and mechanistic features of the
      human MDR-ABC transporters and introduce some of the basic methods that can be
      applied for the analysis of their expression, function, regulation, and
      modulation. We treat in detail the biochemistry, cell biology, and physiology of
      the ABCB1 (MDR1/P-glycoprotein) and the ABCG2 (MXR/BCRP) proteins and describe
      emerging information related to additional ABCB- and ABCG-type transporters with
      a potential role in drug and xenobiotic resistance. Throughout this review we
      demonstrate and emphasize the general network characteristics of the MDR-ABC
      transporters, functioning at the cellular and physiological tissue barriers. In
      addition, we suggest that multidrug transporters are essential parts of an innate
      defense system, the "chemoimmunity" network, which has a number of features
      reminiscent of classical immunology.

PMID- 17015489
TI  - Mechanisms for cellular cholesterol transport: defects and human disease.
AB  - This review summarizes the mechanisms of cellular cholesterol transport and
      monogenic human diseases caused by defects in intracellular cholesterol
      processing. In addition, selected mouse models of disturbed cholesterol
      trafficking are discussed. Current pharmacological strategies to prevent
      atherosclerosis are largely based on altering cellular cholesterol balance and
      are introduced in this context. Finally, because of the organizing potential of
      cholesterol in membranes, disturbances in cellular cholesterol transport have
      implications for a wide variety of human diseases, of which selected examples are
      given.

PMID- 17015490
TI  - Cross-talk between cardiac muscle and coronary vasculature.
AB  - The cardiac muscle and the coronary vasculature are in close proximity to each
      other, and a two-way interaction, called cross-talk, exists. Here we focus on the
      mechanical aspects of cross-talk including the role of the extracellular matrix.
      Cardiac muscle affects the coronary vasculature. In diastole, the effect of the
      cardiac muscle on the coronary vasculature depends on the (changes in) muscle
      length but appears to be small. In systole, coronary artery inflow is impeded, or
      even reversed, and venous outflow is augmented. These systolic effects are
      explained by two mechanisms. The waterfall model and the intramyocardial pump
      model are based on an intramyocardial pressure, assumed to be proportional to
      ventricular pressure. They explain the global effects of contraction on coronary
      flow and the effects of contraction in the layers of the heart wall. The varying
      elastance model, the muscle shortening and thickening model, and the vascular
      deformation model are based on direct contact between muscles and vessels. They
      predict global effects as well as differences on flow in layers and flow
      heterogeneity due to contraction. The relative contributions of these two
      mechanisms depend on the wall layer (epi- or endocardial) and type of contraction
      (isovolumic or shortening). Intramyocardial pressure results from (local) muscle
      contraction and to what extent the interstitial cavity contracts isovolumically.
      This explains why small arterioles and venules do not collapse in systole.
      Coronary vasculature affects the cardiac muscle. In diastole, at physiological
      ventricular volumes, an increase in coronary perfusion pressure increases
      ventricular stiffness, but the effect is small. In systole, there are two
      mechanisms by which coronary perfusion affects cardiac contractility. Increased
      perfusion pressure increases microvascular volume, thereby opening stretch
      activated ion channels, resulting in an increased intracellular Ca2+ transient,
      which is followed by an increase in Ca2+ sensitivity and higher muscle
      contractility (Gregg effect). Thickening of the shortening cardiac muscle takes
      place at the expense of the vascular volume, which causes build-up of
      intracellular pressure. The intracellular pressure counteracts the tension
      generated by the contractile apparatus, leading to lower net force. Therefore,
      cardiac muscle contraction is augmented when vascular emptying is facilitated.
      During autoregulation, the microvasculature is protected against volume changes,
      and the Gregg effect is negligible. However, the effect is present in the right
      ventricle, as well as in pathological conditions with ineffective autoregulation.
      The beneficial effect of vascular emptying may be reduced in the presence of a
      stenosis. Thus cardiac contraction affects vascular diameters thereby reducing
      coronary inflow and enhancing venous outflow. Emptying of the vasculature,
      however, enhances muscle contraction. The extracellular matrix exerts its effect
      mainly on cardiac properties rather than on the cross-talk between cardiac muscle
      and coronary circulation.

PMID- 17015491
TI  - Neuronal control of skin function: the skin as a neuroimmunoendocrine organ.
AB  - This review focuses on the role of the peripheral nervous system in cutaneous
      biology and disease. During the last few years, a modern concept of an
      interactive network between cutaneous nerves, the neuroendocrine axis, and the
      immune system has been established. We learned that neurocutaneous interactions
      influence a variety of physiological and pathophysiological functions, including
      cell growth, immunity, inflammation, pruritus, and wound healing. This
      interaction is mediated by primary afferent as well as autonomic nerves, which
      release neuromediators and activate specific receptors on many target cells in
      the skin. A dense network of sensory nerves releases neuropeptides, thereby
      modulating inflammation, cell growth, and the immune responses in the skin.
      Neurotrophic factors, in addition to regulating nerve growth, participate in many
      properties of skin function. The skin expresses a variety of neurohormone
      receptors coupled to heterotrimeric G proteins that are tightly involved in skin
      homeostasis and inflammation. This neurohormone-receptor interaction is modulated
      by endopeptidases, which are able to terminate neuropeptide-induced inflammatory
      or immune responses. Neuronal proteinase-activated receptors or transient
      receptor potential ion channels are recently described receptors that may have
      been important in regulating neurogenic inflammation, pain, and pruritus.
      Together, a close multidirectional interaction between neuromediators, high
      affinity receptors, and regulatory proteases is critically involved to maintain
      tissue integrity and regulate inflammatory responses in the skin. A deeper
      understanding of cutaneous neuroimmunoendocrinology may help to develop new
      strategies for the treatment of several skin diseases.

PMID- 17015492
TI  - Immunoreactive trypsin/DNA newborn screening for cystic fibrosis: should the
      R117H variant be included in CFTR mutation panels?
AB  - BACKGROUND: Cystic fibrosis newborn screening is now implemented universally in
      France, as well as in many states in the United States and in various areas of
      Europe and Australia. Because the screening protocol usually includes the
      analysis of the most common CFTR mutations, it is of the utmost importance that
      only mutations that result in classical cystic fibrosis are included in this
      test. The panels of mutations used in most cystic fibrosis newborn screening
      programs enable the detection of a relatively frequent CFTR variant (R117H) whose
      implication in cystic fibrosis remains unclear. Physicians, therefore, have
      difficulty managing detected compound heterozygotes with this variant, which
      raises the issue of the appropriateness of extended testing in families and of
      the legitimate use of prenatal diagnosis. OBJECTIVE: The aim of this study was to
      describe the clinical outcome of the children found to be compound heterozygous
      for R117H by screening in Brittany (western France), where cystic fibrosis
      newborn screening was set up in 1989, and to assess whether this CFTR variant
      should be included in the newborn screening mutation panels. METHODS: Data on
      clinical status were obtained by the referring pediatricians. RESULTS: Since our
      screening protocol has enabled detection of R117H (ie, in 1995), 360466 newborns
      have been screened for cystic fibrosis in Brittany, of whom 124 had elevated
      immunoreactive trypsin and 2 mutations in the CFTR gene. Nine of these children
      (7.3%) were compound heterozygous for R117H, which in all cases was linked to the
      7T_11TG haplotype [IVS8-nT variant/m(TG) repeat]. Their genotypes were
      F508del/R117H (n = 7), I507del/R117H (n = 1), or G551D/R117H (n = 1). At the time
      of this writing, the mean age of these 9 children was 7.0 years (the oldest being
      >10 years of age), and none of them had yet developed any signs of cystic
      fibrosis; they have been pancreatic sufficient and have had good nutritional
      status and pulmonary function. Moreover, we observed that, in Brittany, all the
      patients carrying the R117H variant have been identified exclusively through
      cystic fibrosis newborn screening. CONCLUSIONS: In view of the high frequency of
      R117H-7T identified by cystic fibrosis newborn screening, the uncertain outcome
      of the asymptomatic children, and physicians' difficulty in managing these
      situations, we propose the withdrawal of the R117H variant from the panels of
      CFTR mutations used in cystic fibrosis newborn screening, given the expanding
      implementation of cystic fibrosis newborn screening.

PMID- 17015494
TI  - Hyperinsulinemia in healthy children and adolescents with a positive family
      history for type 2 diabetes.
AB  - OBJECTIVE: Our goal was to determine the relationship between family history of
      type 2 diabetes and fasting hyperinsulinemia in healthy children and adolescents.
      METHODS: A total of 317 children and adolescents, 10 to 14 years of age with
      Tanner stage 1 or 2, were randomly selected from elementary and middle schools in
      Durango, northern Mexico, to participate in a cross-sectional, community-based
      study. Family history was ascertained by a direct, detailed medical examination
      that included anthropometric and laboratory measurements from both parents. We
      determined the prevalence of family history of type 2 diabetes, high blood
      pressure, obesity, hyperinsulinemia, and the adjusted odds ratio that computes
      the relationship between hyperinsulinemia and family history of type 2 diabetes.
      RESULTS: Family history of type 2 diabetes, high blood pressure, and obesity was
      recognized in 30 (9.2%), 61 (18.7%), and 74 (22.7%) children and adolescents,
      respectively. Children and adolescents with positive family history showed higher
      systolic and diastolic blood pressure, were more obese, and exhibited
      significantly higher fasting insulin and triglycerides levels, as well as a
      higher homeostasis model analysis insulin resistance index, than children with
      negative family history. A total of 48 (15.1%) children and adolescents exhibited
      hyperinsulinemia, 35 (72.9%) with and 13 (27.1%) without family history. The odds
      ratio adjusted by gender, fat mass (kilograms and percent), waist circumference,
      BMI, and Tanner stage showed that family history of diabetes, but not high blood
      pressure and obesity, was independently related with hyperinsulinemia.
      CONCLUSIONS: Among children and adolescents, family history of diabetes, but not
      high blood pressure and obesity, is independently associated with
      hyperinsulinemia.

PMID- 17015493
TI  - The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and
      literature review of 134 previously reported.
AB  - OBJECTIVE: Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative
      diseases caused by deficiency of lysosomal beta-hexosaminidase resulting in GM2
      ganglioside accumulation in brain. The purpose of this study was to delineate the
      natural history of the condition and identify genotype-phenotype correlations
      that might be helpful in predicting the course of the disease in individual
      patients. METHODS: A cohort of 21 patients with juvenile GM2 gangliosidosis, 15
      with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied
      prospectively in 2 centers. Our experience was compared with previously published
      reports on 134 patients. Information about clinical features, beta-hexosaminidase
      enzyme activity, and mutation analysis was collected. RESULTS: In our cohort of
      patients, the mean (+/-SD) age of onset of symptoms was 5.3 +/- 4.1 years, with a
      mean follow-up time of 8.4 years. The most common symptoms at onset were gait
      disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and
      developmental delay (28.6%). The age of onset of gait disturbances was 7.1 +/-
      5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 +/-
      5.5 years. The mean age of onset of speech problems was 7.0 +/- 5.6 years, with a
      mean time of progression to anarthria of 5.6 +/- 5.3 years. Muscle wasting (10.6
      +/- 7.4 years), proximal weakness (11.1 +/- 7.7 years), and incontinence of
      sphincters (14.6 +/- 9.7 years) appeared later in the course of the disease.
      Psychiatric disturbances and neuropathy were more prevalent in patients with the
      Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia,
      sphincter incontinence, and sleep problems occurred earlier in those with the Tay
      Sachs variant. Cerebellar atrophy was the most common finding on brain MRI
      (52.9%). The median survival time among the studied and reviewed patients was
      14.5 years. The genotype-phenotype correlation revealed that in patients with the
      Tay-Sachs variant, the presence of R178H and R499H mutations was predictive of an
      early onset and rapidly progressive course. The presence of either G269S or W474C
      mutations was associated with a later onset of symptoms along with a more slowly
      progressive disease course. CONCLUSIONS: Juvenile GM2 gangliosidosis is
      clinically heterogeneous, not only in terms of age of onset and clinical features
      but also with regard to the course of the disease. In general, the earlier the
      onset of symptoms, the more rapidly the disease progresses. The Tay-Sachs and
      Sandhoff variants differed somewhat in the frequency of specific clinical
      characteristics. Speech deterioration progressed more rapidly than gait
      abnormalities in both the Tay-Sachs variant and Sandhoff variant groups. Among
      patients with the Tay-Sachs variant, the HEXA genotype showed a significant
      correlation with the clinical course.

PMID- 17015495
TI  - Pharmacokinetics of pyridostigmine in a child with postural tachycardia syndrome.
AB  - Pyridostigmine has been proposed for the treatment of postural orthostatic
      tachycardia syndrome in adults at a dose of 60 mg twice daily, but no dosing
      recommendation exists for children. With the approval of our local ethics board,
      we tested the pharmacokinetics of pyridostigmine in 6 children with myasthenia
      and a pediatric index patient with severe postural orthostatic tachycardia
      syndrome whose condition failed all conventional therapy and who had developed
      significant postural hypertension. Pyridostigmine was quantified by using a
      validated, semiautomated, and specific high-performance liquid
      chromatography/tandem mass spectrometry assay in combination with online column
      switching extraction and turbo electrospray ionization. The patient with postural
      orthostatic tachycardia syndrome showed a dose-dependent favorable response to
      oral pyridostigmine. Pharmacokinetic evaluation revealed a short half-life of
      2.29 hours, similar to the 2.0 +/- 0.63 hours in the patients with myasthenia.
      The patient with postural orthostatic tachycardia syndrome has subsequently been
      treated at a dose of 45 mg in the morning, 30 mg at lunchtime, and 15 mg at
      bedtime; after 9 months, there has been persistent positive effect and without
      additional blood pressure medication. No major adverse effects occurred.
      Pyridostigmine has been a safe and effective treatment modality for this child
      with postural orthostatic tachycardia syndrome. The short half-life suggests that
      dosing 3 times per day is preferable.

PMID- 17015496
TI  - Short-term persistence of high health care costs in a nationally representative
      sample of children.
AB  - OBJECTIVES: Little is known about the persistence of health care costs in
      children. Determining whether children with high health expenses continue to have
      high expenses over time can help in the development of targeted programs and
      policies to decrease costs, plan equitable health insurance strategies, and
      provide insights into the effects of costly conditions on families. The
      objectives of this study were to (1) identify the characteristics of children who
      are in the top 10th percentile for health costs, (2) investigate whether those in
      the top percentiles for costs in 1 year continue in the same percentiles the next
      year, and (3) identify factors that predict whether a child stays in the top
      percentiles. METHODS: Data from 2 consecutive years (2000-2001) of the Medical
      Expenditure Panel Survey were analyzed. Changes in a child's position in the
      expenditure distribution were examined. An estimated multivariate model
      conditional on insurance was developed to predict the true resource costs of
      providing services. Statistical analyses, including logistic-regression and
      multivariate linear-regression modeling, were done to account for the weighted
      sampling used in Medical Expenditure Panel Survey. RESULTS: A total of 2938
      children were included in the survey for both years. In 2000, the top 10% of the
      children accounted for 54% of all costs. They had a mean total expenditure of
      6422 dollars with out-of-pocket expenditures of 1236 dollars; 49% of the children
      in the top decile in 2000 persisted in the top decile in 2001, whereas 12%
      dropped into the bottom half. Children who had been in the top 10% in 2000 were
      10 times more likely than other children to be in the top 10% for 2001. Other
      characteristics in 2000 that predicted membership in the top decile for 2001
      included age (11-15 and 16-17 years), having any insurance (public and private),
      being positive on the standardized Children With Special Health care Need
      screener, and having a functional limitation. CONCLUSIONS: Almost half of the
      children in the top 10% for costs in 2000 persisted in the top 10% in 2001. Older
      children, children with special health care needs, and children with functional
      limitations were more likely to be in the top decile. These findings do not
      support the belief that black and Latino children who are on Medicaid account for
      a disproportionate share of costs or expenditures. Because the children who were
      among the top 10% used health care services in a variety of inpatient, emergency
      department, outpatient, and ancillary venues, providing care coordination
      throughout the entire health care system is important to address both the cost
      and the quality aspects of health care for the most costly children. Targeted
      programs to decrease expenditures for those with the greatest costs have the
      potential to save future health care dollars. Assessment of the factors that
      predict persistence of high expenditures can be used to help in the planning of
      equitable health insurance strategies such as catastrophic care, carve-outs,
      reinsurance, and risk adjustment. Clinicians should review regularly the extent
      of care coordination that they are providing for their high-need and high-cost
      patients, especially preteens and adolescents. Studies that examine the
      persistence of expenditures over longer periods and include assessment of quality
      of care are needed.

PMID- 17015497
TI  - Beverage intake among preschool children and its effect on weight status.
AB  - OBJECTIVE: The obesity epidemic in the United States continues to increase.
      Because obesity tends to track over time, the increase in overweight among young
      children is of significant concern. A number of eating patterns have been
      associated with overweight among preschool-aged children. Recently, 100% fruit
      juice and sweetened fruit drinks have received considerable attention as
      potential sources of high-energy beverages that could be related to the
      prevalence of obesity among young children. Our aim was to evaluate the beverage
      intake among preschool children who participated in the National Health and
      Nutrition Examination Survey 1999-2002 and investigate associations between types
      and amounts of beverages consumed and weight status in preschool-aged children.
      METHODS: We performed a secondary analysis of the data from the National Health
      and Nutrition Examination Survey 1999-2002, which is a continuous, cross
      sectional survey of a nationally representative sample of the
      noninstitutionalized population of the United States. It included the collection
      of parent reported demographic descriptors, a 24-hour dietary recall, a measure
      of physical activity, and a standardized physical examination. The 24-hour
      dietary recall was obtained in person by a trained interviewer and reflected the
      foods and beverages that were consumed by the participant the previous day. The
      National Health and Nutrition Examination Survey food groups were classified on
      the basis of the US Department of Agriculture's Food and Nutrient Database for
      Dietary Studies. We reviewed the main food descriptors used and classified all
      beverages listed. One hundred percent fruit juice was classified as only
      beverages that contained 100% fruit juice, without sweetener. Fruit drinks
      included any sweetened fruit juice, fruit-flavored drink (natural or artificial),
      or drink that contained fruit juice in part. Milk included any type of cow milk
      and then was subcategorized by percentage of milk fat. Any sweetened soft drink,
      caffeinated or uncaffeinated, was categorized as soda. Diet drinks included any
      fruit drink, tea, or soda that was sweetened by low-calorie sweetener. Several
      beverages were removed from the analysis because of low frequency of consumption
      among the sample. Water was not included in the analysis because it is not part
      of the US Department of Agriculture's Food and Nutrient Database categories. For
      the purposes of this analysis, the beverages were converted and reported as
      ounces, rather than grams, as reported by the National Health and Nutrition
      Examination Survey, to make it more clinically relevant. The child's BMI
      percentile for age and gender were calculated on the basis of Centers for Disease
      Control and Prevention criteria and used to identify children's weight status as
      underweight (< 5%), normal weight (5% to < 85%), at risk for overweight (85% to <
      95%), or overweight (> or = 95%). Because of the small number of children in the
      underweight category, they were included in the normal-weight category for this
      analysis. Data were analyzed using SUDAAN 9.0.1 statistical software programs.
      SUDAAN allows for improved accuracy and validity of results by calculating test
      statistics for the stratified, multistage probability design of the National
      Health and Nutrition Examination Survey. Sample weights were applied to all
      analyses to account for unequal probability of selection from oversampling low
      income children and black and Mexican American children. Descriptive and chi2
      analyses and analysis of covariance, adjusting for age, gender, ethnicity,
      household income, energy intake, and physical activity, were conducted. RESULTS:
      All children who were aged 2 to 5 years were identified (N = 1572). Those with
      missing data were removed from additional analysis, resulting in a final sample
      of 1160 preschool children. Of the 1160 children analyzed, 579 (49.9%) were male.
      White children represented 35%, black children represented 28.3%, and Hispanic
      children represented 36.7% of the sample. Twenty-four percent of the children
      were overweight or at risk for overweight (BMI > or = 85%), and 10.7% were
      overweight (BMI > or = 95%). There were no statistically significant differences
      in BMI between boys and girls or among the ethnicities. Overweight children
      tended to be older (mean age: 3.83 years) compared with the normal-weight
      children (mean age: 3.48 years). Eighty-three percent of children drank milk, 48%
      drank 100% fruit juice, 44% drank fruit drink, and 39% drank soda. Whole milk was
      consumed by 46.5% of the children, and 3.1% and 5.5% of the children consumed
      skim milk and 1% milk, respectively. Preschool children consumed a mean total
      beverage volume of 26.93 oz/day, which included 12.32 oz of milk, 4.70 oz of 100%
      fruit juice, 4.98 oz of fruit drinks, and 3.25 oz of soda. Weight status of the
      child had no association with the amount of total beverages, milk, 100% fruit
      juice, fruit drink, or soda consumed. There was no clinically significant
      association between the types of milk (percentage of fat) consumed and weight
      status. In analysis of covariance, daily total energy intake increased with
      increased consumption of milk, 100% fruit juice, fruit drinks, and soda. However,
      there was not a statistically significant increase in BMI on the basis of
      quantity of milk, 100% fruit juice, fruit drink, or soda consumed. CONCLUSIONS:
      On average, preschool children drank less milk than the 2005 Dietary Guidelines
      for Americans recommendation of 16 oz/day. Only 8.6% drank low-fat or skim milk,
      as recommended for children who are older than 2 years. On average, preschool
      children drank < 6 oz/day 100% fruit juice. Increased beverage consumption was
      associated with an increase in the total energy intake of the children but not
      with their BMI. Prospectively studying preschool children beyond 2 to 5 years of
      age, through their adiposity rebound (approximately 5.5-6 years) to determine
      whether there is a trajectory increase in their BMI, may help to clarify the role
      of beverage consumption in total energy intake and weight status.

PMID- 17015498
TI  - Maternal birthplace and breastfeeding initiation among term and preterm infants:
      a statewide assessment for Massachusetts.
AB  - OBJECTIVES: Among premature infants, formula feeding increases the risk for
      necrotizing enterocolitis, delayed brainstem maturation, decreased scoring on
      cognitive and developmental tests, and delayed visual development. With this in
      mind, many interventions are designed to increase breast milk consumption in
      preterm infants. Breastfeeding initiation rates among US premature infants are
      not collected nationally, however, and published data on breastfeeding rates in
      this population are limited. In addition, national surveys calculate
      breastfeeding rates among term infants according to maternal race/ethnicity, but
      maternal birthplace is not recorded. This is likely to be important, because
      breastfeeding is the cultural norm in the countries of origin for many non-US
      born US residents. Massachusetts has a diverse racial/ethnic population,
      including many non-US-born women. The goals of this study were to compare
      breastfeeding initiation rates among preterm and term infants in Massachusetts in
      2002 and to determine the effect of maternal race/ethnicity and birthplace on
      breastfeeding initiation rates among term and preterm infants. METHODS:
      Massachusetts Community Health Information Profile, an online public health
      database that was created by the Massachusetts Department of Public Health,
      includes breastfeeding initiation data that are obtained from the electronic
      birth certificate, which we used to compare breastfeeding rates among preterm and
      term infants. Birth-linked demographics and data that also were accessed were
      maternal age, race/ethnicity, birthplace, and health insurance (public or
      private) as an indicator of socioeconomic status and infant's gestational age. We
      assessed the association between breastfeeding initiation and maternal
      birthplace, as well as race/ethnicity and the other potential confounders, using
      logistic regression. RESULTS: There were 80,624 births in Massachusetts in 2002,
      and 8.2% (6611) of newborns had a gestational age <37 weeks. The state's overall
      breastfeeding initiation rate was 74.6%. We excluded records of mothers who were
      younger than 15 years and older than 39 years, nonsingleton births, infants with
      a gestational age <24 weeks and >42 weeks, and records with missing data. Of the
      total births in Massachusetts, 67,884 (84%) met inclusion criteria for this
      study. Breastfeeding initiation rates were lowest among preterm infants of the
      youngest gestational ages. Breastfeeding initiation was 76.8% among term infants
      born at 37 to 42 weeks, 70.1% among infants born at 32 to 36 weeks, and 62.9%
      among infants born at 24 to 31 weeks. In univariate analysis, among preterm
      infants, a lower proportion of US-born black, Asian, and Hispanic mothers
      initiated breastfeeding than US-born white mothers; non-US-born black and non-US
      born Hispanic mothers had the highest breastfeeding initiation rates. Among term
      infants, US-born black mothers had the lowest initiation rates, and non-US-born
      black and non-US-born Hispanic mothers had the highest. In multivariate logistic
      regression, however, after controlling for mother's age, race, birthplace, and
      insurance, US-born white mothers were least likely to breastfeed either term or
      preterm infants when compared with any other racial/ethnic group, including US
      born black mothers. The likelihood that non-US-born Hispanic mothers would
      breastfeed was almost 8 times greater than that for US-born white mothers for a
      preterm infant and almost 10 times greater for a term infant. In multivariate
      logistic regression analysis stratified by gestational age for both preterm and
      term infants, older mothers and mothers with private health insurance were most
      likely to breastfeed. CONCLUSIONS: In Massachusetts, preterm infants were less
      likely to receive breast milk than term infants, and the likelihood of receiving
      breast milk was lowest among the youngest preterm infants. In multivariate
      logistic regression, mothers who were born outside the United States were more
      likely than US-born mothers to breastfeed either term or preterm infants in all
      racial and ethnic groups. In an unexpected finding, US-born white mothers were
      less likely to breastfeed term or preterm infants than US-born black mothers or
      mothers of any other racial or ethnic group.

PMID- 17015499
TI  - Association between television, movie, and video game exposure and school
      performance.
AB  - BACKGROUND: The relationship between media exposure and school performance has
      not been studied extensively in adolescents. OBJECTIVE: The purpose of this work
      was to test the relative effects of television, movie, and video game screen time
      and content on adolescent school performance. METHODS: We conducted a population
      based cross-sectional survey of middle school students (grades 5-8) in the
      Northeastern United States. We looked at weekday television and video game screen
      time, weekend television and video game screen time, cable movie channel
      availability, parental R-rated movie restriction, and television content
      restriction. The main outcome was self-report of school performance (excellent,
      good, average, or below average). We used ordinal logistic-regression analysis to
      test the independent effects of each variable, adjusting for demographics, child
      personality, and parenting style. RESULTS: There were 4508 students who
      participated in the study; gender was equally represented, and 95% were white. In
      multivariate analyses, after adjusting for other covariates, the odds of poorer
      school performance increased with increasing weekday television screen time and
      cable movie channel availability and decreased with parental restriction of
      television content restriction. As compared with children whose parents never
      allowed them to watch R-rated movies, children who watched R-rated movies once in
      a while, sometimes, or all of the time had significantly increased cumulative
      odds of poorer school performance. Weekend screen time and video game use were
      not associated with school performance. CONCLUSIONS: We found that both content
      exposure and screen time had independent detrimental associations with school
      performance. These findings support parental enforcement of American Academy of
      Pediatrics guidelines for media time (particularly weekdays) and content limits
      to enhance school success.

PMID- 17015500
TI  - Delaying second births among adolescent mothers: a randomized, controlled trial
      of a home-based mentoring program.
AB  - CONTEXT: Rates of rapid second births among low-income black adolescent mothers
      range from 20% to 50%. Most efforts to prevent rapid second births have been
      unsuccessful. OBJECTIVES: There were 4 objectives: (1) to examine whether a home
      based mentoring intervention was effective in preventing second births within 2
      years of the adolescent mother's first delivery; (2) to examine whether greater
      intervention participation increased the likelihood of preventing a second birth;
      (3) to examine whether second births were better predicted from a risk practice
      perspective or a family formation perspective, based on information collected at
      delivery; and (4) to examine how risk practices or family formation over the
      first 2 years of parenthood were related to a second birth. DESIGN: We conducted
      a randomized, controlled trial of a home-based intervention curriculum, based on
      social cognitive theory, and focused on interpersonal negotiation skills,
      adolescent development, and parenting. The curriculum was delivered biweekly
      until the infant's first birthday by college-educated, black, single mothers who
      served as mentors, presenting themselves as "big sisters." The control group
      received usual care. Follow-up evaluations were conducted in the homes 6, 13, and
      24 months after recruitment. METHODS: Participants were recruited from urban
      hospitals at delivery and were 181 first time, black adolescent mothers (< 18
      years of age); 82% (149 of 181) completed the 24-month evaluation. RESULTS:
      Intent-to-treat analyses revealed that control mothers were more likely than
      intervention mothers to have a second infant. The complier average causal effect
      was used to account for variability in intervention participation. Having > or =
      2 intervention visits increased the odds of not having a second infant more than
      threefold. Only 1 mother who completed > or = 6 visits had a second infant. At
      delivery of their first infant, mothers who had a second infant were slightly
      older (16.7 vs 16.2 years) and were more likely to have been arrested (30% vs
      14%). There were no differences in baseline contraceptive use or other measures
      of risk or family formation. At 24 months, mothers who had a second infant
      reported high self-esteem, positive life events, and romantic involvement and
      residence with the first infant's father. At 24 months, there were no differences
      in marital rates (2%), risk practices, or contraceptive use between mothers who
      did and did not have a second infant. Mothers who did not have a second infant
      were marginally more likely to report no plans for contraception in their next
      sexual contact compared with mothers who had a second infant (22% vs 8%,
      respectively). CONCLUSIONS: A home-based intervention founded on a mentorship
      model and targeted toward adolescent development, including negotiation skills,
      was effective in preventing rapid repeat births among low-income, black
      adolescent mothers. The effectiveness of the intervention could be seen after
      only 2 visits and increased over time. There were no second births among mothers
      who attended > or = 8 sessions. There was no evidence that risk behavior or
      contraceptive use was related to rapid second births. There was some evidence
      that rapid second births among adolescent mothers were regarded as desirable and
      as part of a move toward increasing autonomy and family formation, thereby
      undermining intervention programs that focus on risk avoidance. Findings suggest
      the merits of a mentoring program for low-income, black adolescent mothers, based
      on a relatively brief (6-8 sessions) curriculum targeted toward adolescent
      development and interpersonal negotiation skills.

PMID- 17015502
TI  - A Delphi approach to reach consensus on primary care guidelines regarding youth
      violence prevention.
AB  - OBJECTIVE: Anticipatory guidance is a cornerstone of modern pediatric practice.
      In recognition of its importance for child well being, injury prevention
      counseling is a standard element of that guidance. Over the last 20 years, there
      has been growing recognition that intentional injury or violence is one of the
      leading causes of morbidity and mortality among youth. The US Surgeon General
      identified youth violence as a major public health issue and a top priority. Yet,
      only recently has the scope of injury prevention counseling been expanded to
      include violence. Pediatric health care providers agree that youth violence
      prevention counseling should be provided, yet the number of topics available, the
      already lengthy list of other anticipatory guidance topics to be covered,
      developmental considerations, and the evidence base make the selection of an
      agreed-on set a considerable challenge. The purpose of this study was to
      systematically identify and prioritize specific counseling topics in violence
      prevention that could be integrated into anticipatory guidance best practice.
      DESIGN: A modified electronic Delphi process was used to gain consensus among 50
      national multidisciplinary violence-prevention experts. Participants were unaware
      of other participants' identities. METHODS: The process consisted of 4 serial
      rounds of inquiry beginning with a broad open-ended format for the generation of
      anticipatory guidance and screening topics across 5 age groups (infant, toddler,
      school age, adolescent, and all ages). Each subsequent round narrowed the list of
      topics toward the development of a manageable set of essential topics for
      screening and counseling about positive youth development and violence
      prevention. RESULTS: Forty-seven unique topics were identified, spanning birth to
      age 21 years. Topics cover 4 broad categories (building blocks): physical safety,
      parent centered, child centered, and community connection. Participants placed
      topics into their developmentally appropriate visit-based schedule and made
      suggestions for an appropriate topic reinforcement schedule. The resulting
      schedule provides topics for introduction and reinforcement at each visit.
      CONCLUSIONS: The Delphi technique proved a useful approach for accessing expert
      opinion, for analyzing and synthesizing results, for achieving consensus, and for
      setting priorities among the numerous anticipatory guidance and assessment topics
      relevant for raising resilient, violence-free youth.

PMID- 17015501
TI  - Increased cerebral blood flow velocity in children with mild sleep-disordered
      breathing: a possible association with abnormal neuropsychological function.
AB  - OBJECTIVE: Sleep-disordered breathing describes a spectrum of upper airway
      obstruction in sleep from simple primary snoring, estimated to affect 10% of
      preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence
      has challenged previous assumptions that primary snoring is benign. A recent
      report identified reduced attention and higher levels of social problems and
      anxiety/depressive symptoms in snoring children compared with controls.
      Uncertainty persists regarding clinical thresholds for medical or surgical
      intervention in sleep-disordered breathing, underlining the need to better
      understand the pathophysiology of this condition. Adults with sleep-disordered
      breathing have an increased risk of cerebrovascular disease independent of
      atherosclerotic risk factors. There has been little focus on cerebrovascular
      function in children with sleep-disordered breathing, although this would seem an
      important line of investigation, because studies have identified abnormalities of
      the systemic vasculature. Raised cerebral blood flow velocities on transcranial
      Doppler, compatible with raised blood flow and/or vascular narrowing, are
      associated with neuropsychological deficits in children with sickle cell disease,
      a condition in which sleep-disordered breathing is common. We hypothesized that
      there would be cerebral blood flow velocity differences in sleep-disordered
      breathing children without sickle cell disease that might contribute to the
      association with neuropsychological deficits. DESIGN: Thirty-one snoring children
      aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17
      control children were identified through a local Sunday school or as siblings of
      cases. Children with craniofacial abnormalities, neuromuscular disorders,
      moderate or severe learning disabilities, chronic respiratory/cardiac conditions,
      or allergic rhinitis were excluded. Severity of sleep-disordered breathing in
      snoring children was categorized by attended polysomnography. Weight, height, and
      head circumference were measured in all of the children. BMI and occipitofrontal
      circumference z scores were computed. Resting systolic and diastolic blood
      pressure were obtained. Both sleep-disordered breathing children and the age- and
      BMI-similar controls were assessed using the Behavior Rating Inventory of
      Executive Function (BRIEF), Neuropsychological Test Battery for Children (NEPSY)
      visual attention and visuomotor integration, and IQ assessment (Wechsler
      Preschool and Primary Scale of Intelligence Version III). Transcranial Doppler
      was performed using a TL2-64b 2-MHz pulsed Doppler device between 2 pm and 7 pm
      in all of the patients and the majority of controls while awake. Time-averaged
      mean of the maximal cerebral blood flow velocities was measured in the left and
      right middle cerebral artery and the higher used for analysis. RESULTS: Twenty
      one snoring children had an apnea/hypopnea index <5, consistent with mild sleep
      disordered breathing below the conventional threshold for surgical intervention.
      Compared with 17 nonsnoring controls, these children had significantly raised
      middle cerebral artery blood flow velocities. There was no correlation between
      cerebral blood flow velocities and BMI or systolic or diastolic blood pressure
      indices. Exploratory analyses did not reveal any significant associations with
      apnea/hypopnea index, apnea index, hypopnea index, mean pulse oxygen saturation,
      lowest pulse oxygen saturation, accumulated time at pulse oxygen saturation <90%,
      or respiratory arousals when examined in separate bivariate correlations or in
      aggregate when entered simultaneously. Similarly, there was no significant
      association between cerebral blood flow velocities and parental estimation of
      child's exposure to sleep-disordered breathing. However, it is important to note
      that whereas the sleep-disordered breathing group did not exhibit significant
      hypoxia at the time of study, it was unclear to what extent this may have been a
      feature of their sleep-disordered breathing in the past. IQ measures were in the
      average range and comparable between groups. Measures of processing speed and
      visual attention were significantly lower in sleep-disordered breathing children
      compared with controls, although within the average range. There were similar
      group differences in parental-reported executive function behavior. Although
      there were no direct correlations, adjusting for cerebral blood flow velocities
      eliminated significant group differences between processing speed and visual
      attention and decreased the significance of differences in Behavior Rating
      Inventory of Executive Function scores, suggesting that cerebral hemodynamic
      factors contribute to the relationship between mild sleep-disordered breathing
      and these outcome measures. CONCLUSIONS: Cerebral blood flow velocities measured
      by noninvasive transcranial Doppler provide evidence for increased cerebral blood
      flow and/or vascular narrowing in childhood sleep-disordered breathing; the
      relationship with neuropsychological deficits requires further exploration. A
      number of physiologic changes might alter cerebral blood flow and/or vessel
      diameter and, therefore, affect cerebral blood flow velocities. We were able to
      explore potential confounding influences of obesity and hypertension, neither of
      which explained our findings. Second, although cerebral blood flow velocities
      increase with increasing partial pressure of carbon dioxide and hypoxia, it is
      unlikely that the observed differences could be accounted for by arterial blood
      gas tensions, because all of the children in the study were healthy, with no
      cardiorespiratory disease, other than sleep-disordered breathing in the snoring
      group. Although arterial partial pressure of oxygen and partial pressure of
      carbon dioxide were not monitored during cerebral blood flow velocity
      measurement, assessment was undertaken during the afternoon/early evening when
      the child was awake, and all of the sleep-disordered breathing children had
      normal resting oxyhemoglobin saturation at the outset of their subsequent sleep
      studies that day. Finally, there is an inverse linear relationship between
      cerebral blood flow and hematocrit in adults, and it is known that iron-deficient
      erythropoiesis is associated with chronic infection, such as recurrent
      tonsillitis, a clinical feature of many of the snoring children in the study.
      Preoperative full blood counts were not performed routinely in these children,
      and, therefore, it was not possible to exclude anemia as a cause of increased
      cerebral blood flow velocity in the sleep-disordered breathing group. However,
      hemoglobin levels were obtained in 4 children, 2 of whom had borderline low
      levels (10.9 and 10.2 g/dL). Although there was no apparent relationship with
      cerebral blood flow velocity in these children (cerebral blood flow velocity
      values of 131 and 130 cm/second compared with 130 and 137 cm/second in the 2
      children with normal hemoglobin levels), this requires verification. It is of
      particular interest that our data suggest a relationship among snoring, increased
      cerebral blood flow velocities and indices of cognition (processing speed and
      visual attention) and perhaps behavioral (Behavior Rating Inventory of Executive
      Function) function. This finding is preliminary: a causal relationship is not
      established, and the physiologic mechanisms underlying such a relationship are
      not clear. Prospective studies that quantify cumulative exposure to the
      physiologic consequences of sleep-disordered breathing, such as hypoxia, would be
      informative.

PMID- 17015503
TI  - The psychosocial problems of children with narcolepsy and those with excessive
      daytime sleepiness of uncertain origin.
AB  - BACKGROUND: Narcolepsy is a predominantly rapid eye movement sleep disorder with
      onset usually in the second decade but often in earlier childhood. Classically it
      is characterized by combinations of excessive sleepiness especially sleep
      attacks, cataplexy, hypnagogic hallucinations, and sleep paralysis. The
      psychosocial effects of this lifelong condition are not well documented,
      especially in children. This study aims to describe the psychosocial profile of a
      large group of children with narcolepsy compared with other excessively sleepy
      children and controls. METHODS: We used an international cross-sectional
      questionnaire survey of children aged from 4 to 18 years who had received from a
      physician a diagnosis of narcolepsy compared with age- and gender-matched
      controls. Assessments were made of behavior, mood, quality of life, and
      educational aspects. RESULTS: Recruited children were separated into those who
      met conventional criteria for narcolepsy (n = 42) and those whose primary
      complaint was excessive daytime sleepiness without definite additional features
      of narcolepsy (excessive daytime sleepiness group; n = 18). Compared with
      controls, children with narcolepsy and also those with excessive daytime
      sleepiness alone showed significantly higher rates of behavioral problems and
      depression. Again, to a significant extent, their quality of life was poorer and
      they had more educational problems. The children with narcolepsy and the
      excessive daytime sleepiness group were indistinguishable from each other on
      these measures. CONCLUSIONS: A range of psychosocial problems can be identified
      in children with narcolepsy. The origins of these problems are unclear. The
      similar profiles of difficulties in the narcolepsy and excessive daytime
      sleepiness groups suggest that excessive sleepiness is the main cause. Clinicians
      and others responsible for the care of such children need to be mindful of the
      importance of early detection, intervention, and, ideally, the prevention of
      these problems.

PMID- 17015504
TI  - Risk reduction for adverse drug events through sequential implementation of
      patient safety initiatives in a children's hospital.
AB  - BACKGROUND: Medication management is a complex, multifaceted system. Prescribing
      errors occur upstream in the process, and as such, their effects can be
      perpetuated, and sometimes even exacerbated, in subsequent steps. These errors
      place patients at risk of adverse drug events. Children, especially young
      infants, are at particular risk because of their size, unique physiology, and
      immature ability to metabolize drugs. OBJECTIVE: The purpose of this study was to
      reduce the risk of harm to children resulting from prescribing errors. METHODS:
      We sequentially implemented patient safety initiatives over a 1-year time frame
      at a pediatric tertiary care academic facility. The initiatives included an
      educational Web site with competency examination, distribution of a personal
      digital assistant-based standardized dosing reference, a zero-tolerance policy
      for incomplete or incorrect medication orders, prescriber performance feedback,
      and presentation of outcome data at citywide grand rounds. A total of 8718 orders
      were collected and analyzed to assess the impact of these initiatives. RESULTS:
      The absolute risk reduction from prescribing errors was 38 per 100 orders, with a
      relative risk reduction of 49%. Web-based education with point-of-care drug
      references and a zero-tolerance policy for incomplete or incorrect orders were
      most effective in decreasing potential adverse drug events. Documentation of
      appropriate weight-based dosing and indication for therapy increased by 24% and
      42%, respectively. CONCLUSIONS: Process-improvement initiatives focusing on
      prescriber education and behavior modification can reduce the risk of harm to
      pediatric patients from prescribing errors.

PMID- 17015505
TI  - Examining characteristics and associated distress related to Internet harassment:
      findings from the Second Youth Internet Safety Survey.
AB  - OBJECTIVE: We sought to identify the characteristics of youth who are targets of
      Internet harassment and characteristics related to reporting distress as a result
      of the incident. PARTICIPANTS AND METHODS: The Second Youth Internet Safety
      Survey is a national telephone survey of a random sample of 1500 Internet users
      between the ages of 10 and 17 years conducted between March and June 2005.
      Participants had used the Internet at least once a month for the previous 6
      months. RESULTS: Nine percent of the youth who used the Internet were targets of
      online harassment in the previous year. Thirty-two percent of the targets
      reported chronic harassment (ie, harassment > or = 3 times in the previous year).
      In specific incidents, almost half (45%) knew the harasser in person before the
      incident. Half of the harassers (50%) were reportedly male, and half (51%) were
      adolescents. One in 4 targets reported an aggressive offline contact (eg, the
      harasser telephoned, came to the youth's home, or sent gifts); 2 in 3 disclosed
      the incident to another person. Among otherwise similar youth, the odds of being
      a target of Internet harassment were higher for those youth who harassed others
      online, reported borderline/clinically significant social problems, and were
      victimized in other contexts. Likewise, using the Internet for instant messaging,
      blogging, and chat room use each elevated the odds of being a target of Internet
      harassment versus those who did not engage in these online activities. All other
      demographic, Internet-use, and psychosocial characteristics were not related to
      reports of online harassment. Thirty-eight percent of the harassed youth reported
      distress as a result of the incident. Those who were targeted by adults, asked to
      send a picture of themselves, received an aggressive offline contact (eg, the
      harasser telephoned or came to the youth's home), and were preadolescents were
      each significantly more likely to report distress because of the experience.
      Conversely, the youth who visited chat rooms were significantly less likely to be
      distressed by the harassment. CONCLUSIONS: Internet harassment can be a serious
      event for some youth. Because there has been a significant increase in the
      prevalence of Internet harassment from 2000 to 2005, adolescent health
      professionals should continue to be vigilant about such experiences in the lives
      of young people with whom they interact. Social problems and online aggressive
      behavior are each associated with elevated odds of being the target of
      harassment. Thus, prevention efforts may be best aimed at improving the
      interpersonal skills of young people who choose to communicate with others using
      these online tools. Adolescent health professionals should be especially aware of
      events that include aggressive offline contacts by adult harassers or asking the
      child or adolescent to send a picture of themselves, because each of these
      scenarios increase the odds of reporting distress by more than threefold.
      Findings further support the call for the inclusion of Internet-harassment
      prevention in conventional antibullying programs empowering schools to address
      Internet bullying situations that occur between students. This will not solve all
      situations, however. We also must encourage Internet service providers to partner
      with consumers to be proactive in serious harassment episodes that violate
      criminal laws and service-provider codes of conduct.

PMID- 17015506
TI  - Screening for developmental delay in the setting of a community pediatric clinic:
      a prospective assessment of parent-report questionnaires.
AB  - OBJECTIVES: Our goal for this study was to prospectively test whether parent
      completed questionnaires can be effectively used in the setting of a busy
      ambulatory pediatric clinic to accurately screen for developmental impairments.
      Specific objectives included (1) assessing the feasibility of using parent-report
      instruments in the setting of a community pediatric clinic, (2) evaluating the
      accuracy of 2 available screening tests (the Ages and Stages Questionnaire and
      Child Development Inventory), and (3) ascertaining if the pediatrician's clinical
      judgment could be used as a potential modifier. METHODS: Subjects were recruited
      from the patient population of a community clinic providing primary ambulatory
      pediatric care. Subjects without previous developmental delay or concerns noted
      were contacted at the time of their routine 18-month-old visit. Those subjects
      who agreed to participate were randomly assigned to 1 of 2 groups and completed
      either the Ages and Stages Questionnaire or Child Development Inventory. The
      child's pediatrician also completed a brief questionnaire regarding his or her
      opinion of the child's development. Those children for whom concerns were
      identified by either questionnaire underwent additional detailed testing by the
      Battelle Development Inventory, the "gold standard" for the purposes of this
      study. An equal number of children scoring within the norms of the screening
      measures also underwent testing with the Battelle Development Inventory. RESULTS:
      Of the 356 parents contacted, 317 parents (90%) agreed to participate. Most
      parents correctly completed the Ages and Stages Questionnaire (81%) and the Child
      Development Inventory (75%). Predictive values were calculated for the Ages and
      Stages Questionnaire and the Child Development Inventory (sensitivity: 0.67 and
      0.50; specificity: 0.39 and 0.86; positive predictive value: 34% and 50%;
      negative predictive value: 71% and 86%, respectively). Incorporating the
      physician's opinion regarding the developmental status of the child did not
      improve the accuracy of the screening questionnaires. CONCLUSIONS: Three
      important conclusions were reached: (1) parent-completed questionnaires can be
      feasibly used in the setting of a pediatric clinic; (2) the pediatrician's
      opinion had little effect in ameliorating the accuracy of either questionnaire;
      and (3) single-point accuracy of these screening instruments in a community
      setting did not meet the requisite standard for development screening tests as
      set by current recommendations. This study raises important questions about how
      developmental screening can be performed, and we recommend additional research to
      elucidate a successful screening procedure.

PMID- 17015507
TI  - Cost of outpatient medical care for children and youth with special health care
      needs: investigating the impact of the medical home.
AB  - OBJECTIVE: Our goal was to evaluate the impact of having a medical home on the
      outpatient medical costs of children and youth with special health care needs.
      DESIGN: Data from 2 sources were matched at the individual level: (1) the 2002
      Iowa Consumer Assessment of Health Plans Study survey of Medicaid enrollees and
      (2) Iowa Medicaid administrative claims, encounter, and enrollment files.
      PARTICIPANTS: The subjects were 1140 children aged 6 months to 12 years for whom
      both sources of data were available. MAIN OUTCOME MEASURE(S): Outcomes measures
      included medical homeness, as developed by a scale of items in the Consumer
      Assessment of Health Plans Study survey, and outpatient costs, as determined from
      Medicaid administrative data. RESULTS: From the regression models, we found that
      (1) for all Medicaid-enrolled children, outpatient costs were significantly
      higher for female children and children and youth with special health care needs,
      (2) for children and youth without special health care needs, costs were
      significantly higher for female children, those with a personal doctor or nurse,
      and those with more of a medical home, and (3) for children and youth with
      special health care needs, costs were significantly higher for those in a lower
      health state, for those in health maintenance organization 2, and for older
      children. CONCLUSIONS: Although the degree of medical homeness was not related to
      outpatient costs for children and youth with special health care needs, medical
      homeness may affect inpatient costs more than outpatient costs for children and
      youth with special health care needs and should be investigated further.

PMID- 17015508
TI  - A comparison of health care utilization and costs of children with and without
      autism spectrum disorders in a large group-model health plan.
AB  - OBJECTIVE: Data on the current costs of medical services for children with autism
      spectrum disorders are lacking. Our purpose for this study was to compare health
      care utilization and costs of children with and without autism spectrum disorders
      in the same health plan. PATIENTS AND METHODS: Participants included all 2- to 18
      year-old children with autism spectrum disorders (n = 3053) and a random sample
      of children without autism spectrum disorders (n = 30529) who were continuously
      enrolled in the Kaiser Permanente Medical Care Program in northern California
      between July 1, 2003, and June 30, 2004. Data on health care utilization and
      costs were derived from health plan administrative databases. MAIN OUTCOME
      MEASURES: Outcome measures included mean annual utilization and costs of health
      services per child. RESULTS: Children with autism spectrum disorders had a higher
      annual mean number of total clinic (5.6 vs 2.8), pediatric (2.3 vs 1.6), and
      psychiatric (2.2 vs 0.3) outpatient visits. A higher percentage of children with
      autism spectrum disorders experienced inpatient (3% vs 1%) and outpatient (5% vs
      2%) hospitalizations. Children with autism spectrum disorders were nearly 9 times
      more likely to use psychotherapeutic medications and twice as likely to use
      gastrointestinal agents than children without autism spectrum disorders. Mean
      annual member costs for hospitalizations (550 dollars vs 208 dollars), clinic
      visits (1373 dollars vs 540 dollars), and prescription medications (724 dollars
      vs 96 dollars) were more than double for children with autism spectrum disorders
      compared with children without autism spectrum disorders. The mean annual age-
      and gender-adjusted total cost per member was more than threefold higher for
      children with autism spectrum disorders (2757 dollars vs 892 dollars). Among the
      subgroup of children with other psychiatric conditions, total mean annual costs
      were 45% higher for children with autism spectrum disorders compared with
      children without autism spectrum disorders; excess costs were largely explained
      by the increased use of psychotherapeutic medications. CONCLUSIONS: The
      utilization and costs of health care are substantially higher for children with
      autism spectrum disorders compared with children without autism spectrum
      disorders. Research is needed to evaluate the impact of improvements in the
      management of children with autism spectrum disorders on health care utilization
      and costs.

PMID- 17015509
TI  - Bullying and peer victimization among children with special health care needs.
AB  - BACKGROUND: Dr Van Cleave's current address is Department of Pediatrics, Center
      for Child and Adolescent Health Policy, MassGeneral Hospital for Children, 50
      Staniford St, Room 901, Boston, MA 02114. The association between bullying, being
      bullied, or being a bully/victim and having a special health care need has not
      been well described in a national sample of children with a broad variety of
      special needs. OBJECTIVE: We aimed to determine the prevalence of bullying, being
      bullied, or being a bully/victim in children with special health care needs and
      associations of behaviors with particular types of special needs. DESIGN: We
      performed a secondary data analysis using the National Survey of Children's
      Health, a nationally representative telephone survey conducted by the National
      Center for Health Statistics of >102,000 US households. METHODS: We measured
      associations between having a special health care need and being a victim of
      bullying, bullying other children, and being a bully/victim in children and
      adolescents aged 6 to 17 years. Multiple logistic-regression models were used to
      examine the association of children with special health care needs overall, and
      of particular special needs, with the bullying measures. RESULTS: Overall,
      children with special health care needs were 21% of the population. In
      multivariate models adjusting for sociodemographic factors, being a child with
      special health care needs was associated with being bullied but not with bullying
      or being a bully/victim. Having a chronic behavioral, emotional, or developmental
      problem was associated with bullying others and with being a bully/victim.
      CONCLUSIONS: Having a special health care need generally is associated with being
      bullied, and having a behavioral, emotional, or developmental problem is
      associated with bullying others and being a bully/victim. These findings may help
      pediatricians, mental health providers, and schools use targeted screening and
      interventions to address bullying for children with special health care needs.

PMID- 17015510
TI  - Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in
      girls with Turner syndrome.
AB  - BACKGROUND: We recently reported that electrocardiographic abnormalities are
      common in adults with monosomy X (Turner syndrome), but this issue has not been
      investigated in girls with Turner syndrome. PATIENTS AND METHODS: We analyzed
      electrocardiograms in 78 girls with Turner syndrome and 50 age-matched control
      girls. The girls with Turner syndrome had additional cardiac and metabolic
      evaluations. RESULTS: Girls with Turner syndrome were more likely to demonstrate
      > or = 1 electrocardiographic findings including right axis deviation, right
      ventricular hypertrophy, accelerated atrioventricular conduction, T-wave
      abnormalities, and a prolonged rate-corrected QT interval. The right-sided
      findings were associated with partial anomalous pulmonary venous connection, but
      the etiology of the other findings remains unknown. The rate-corrected QT
      interval was significantly longer in girls with Turner syndrome (431 +/- 22 vs
      407 +/- 21 milliseconds). Twenty-eight girls with Turner syndrome but only 2
      controls had a rate-corrected QT interval above the reference range. We found no
      correlation between body habitus, cardiac dimensions, or metabolic parameters and
      the rate-corrected QT interval duration in girls with Turner syndrome.
      CONCLUSIONS: Cardiac conduction and repolarization abnormalities seem to affect
      both young girls and adults with Turner syndrome equally, suggesting that
      electrophysiologic defects are intrinsic to the syndrome and indicating that
      electrocardiogram analysis should be included in evaluating and monitoring even
      the youngest patients with Turner syndrome. Attention to the rate-corrected QT
      interval is important, because some common medications may further prolong this
      interval and increase the risk of arrhythmias.

PMID- 17015511
TI  - Development of hand function and precision grip control in individuals with
      cerebral palsy: a 13-year follow-up study.
AB  - OBJECTIVE: Although children with cerebral palsy display large developmental
      differences in hand function from that of typically developing children by the
      age of 6 to 10 years, little is known about the developmental processes
      underlying hand function during subsequent development. In this study we
      investigated the development of manual dexterity in a timed motor task, the
      timing and amplitude of fingertip-force application during a precision grasping
      task, and the relationship between changes in these measures. We applied highly
      quantitative analytical approaches to determine if the fingertip-force
      application pattern and trial-to-trial variation of fingertip-force application
      change during development. METHODS: Twelve subjects with cerebral palsy (aged 6-8
      years) participated in the first data-collection session conducted between 1989
      and 1990. Ten of these subjects (5 with hemiplegia and 5 with diplegia, aged 19
      21 years) returned between 2002 and 2003. Manual dexterity was measured by using
      timed tasks of the Jebsen-Taylor test of hand function. Subjects also lifted an
      object instrumented with force transducers while we measured the temporal
      coordination of fingertip coordination and the path ratio between the grip and
      vertical load-force trajectory (straightness). We used generalized procrustes
      analysis to determine if there were changes in shape of the force trajectory and
      intertrial variability. RESULTS: The Jebsen-Taylor test times decreased 45% from
      the first to the second data session. The overall time to complete the grip-lift
      task decreased 22%, mainly because of a faster transition from grasp to lift. The
      grip-force/load-force path ratios decreased from 1.7 to 1.35 (1 = straight line).
      Generalized procrustes analysis indicated a change in the shape and a decrease in
      variability in shape of the force-ratio path. CONCLUSIONS: Our results
      demonstrate that the efficiency in grasping had developed during a 13-year period
      for this small group of participants with cerebral palsy, which suggests that
      improvement in hand function occurs over a longer time frame than commonly would
      be expected.

PMID- 17015512
TI  - Position statement: Continuous subcutaneous insulin infusion in very young
      children with type 1 diabetes.
AB  - Insulin pump therapy has become increasingly popular for the treatment of type 1
      diabetes in pediatric patients. Although significant experience has accrued with
      the use of this modality in older children and adolescents, much less data are
      available regarding continuous subcutaneous insulin infusion in the very young.
      Policies of individual physician practices and insurance companies vary widely,
      and there is currently no consensus regarding the appropriateness of insulin pump
      therapy in the under 6 age group. However, we have witnessed in recent years a
      significant increase in the number of clinical trials investigating the use of
      continuous subcutaneous insulin infusion in young patients, and reports of > 100
      preschool-aged diabetic children treated with insulin pumps are available in the
      literature. Although these studies have been of relatively short duration (< or =
      12 months), the results are remarkably consistent. Although there is no evidence
      that insulin pump therapy results in a sustained improvement in glycemic control
      in this age group, risks associated with these devices in the hands of reliable
      adults who are managing diabetes in very young children are low. Parental
      satisfaction related to the increased flexibility that continuous subcutaneous
      insulin infusion affords anecdotally seems to be high, although formal
      examination of parental stress and health-related quality of life in this setting
      has been minimal. Important questions remain regarding selection of appropriate
      candidates for insulin pump therapy, whether benefits of continuous subcutaneous
      insulin infusion outweigh the costs, and what eventual outcomes will be in
      children treated with pumps from a very young age. Long-term follow-up of
      medical, psychological, and neurocognitive parameters in these young patients
      will be paramount. Our goal with this review is to summarize efficacy and safety
      of continuous subcutaneous insulin infusion in children < or = 6 years of age,
      present potential pros and cons of using insulin pumps in this population, and
      propose clinical management guidelines that could be useful for both
      practitioners and third-party payers alike.

PMID- 17015513
TI  - Report of the Tennessee Task Force on Screening Newborn Infants for Critical
      Congenital Heart Disease.
AB  - A member of the Tennessee state legislature recently proposed a bill that would
      mandate all newborn infants to undergo pulse oximetry screening for the purpose
      of identifying those with critical structural heart disease before discharge
      home. The Tennessee Task Force on Screening Newborn Infants for Critical
      Congenital Heart Defects was convened on September 29, 2005. This group reviewed
      the current medical literature on this topic, as well as data obtained from the
      Tennessee Department of Health, and debated the merits and potential detriments
      of a statewide screening program. The estimated incidence of critical congenital
      heart disease is 170 in 100,000 live births, and of those, 60 in 100,000 infants
      have ductal-dependent left-sided obstructive lesions with the potential of
      presentation by shock or death if the diagnosis is missed. Of the latter group,
      the diagnosis is missed in approximately 9 in 100,000 by fetal ultrasound
      assessment and discharge examination and might be identified by a screening
      program. Identification of the missed diagnosis in these infants before discharge
      could spare many of them death or neurologic sequelae. Four major studies using
      pulse oximetry screening were analyzed, and when data were restricted to critical
      left-sided obstructive lesions, sensitivity values of 0% to 50% and false
      positive rates of between 0.01% and 12% were found in asymptomatic populations.
      Because of this variability and other considerations, a meaningful cost/benefit
      analysis could not be performed. It was the consensus of the task force to
      provide a recommendation to the legislature that mandatory screening not be
      implemented at this time. In addition, we determined that a very large,
      prospective, perhaps multistate study is needed to define the sensitivity and
      false-positive rates of lower-limb pulse oximetry screening in the asymptomatic
      newborn population and that there needs to be continued partnering between the
      medical community, parents, and local, state, and national governments in
      decisions regarding mandated medical care.

PMID- 17015514
TI  - Forty years in partnership: the American Academy of Pediatrics and the Indian
      Health Service.
AB  - Fifty years ago, American Indian and Alaska Native children faced an overwhelming
      burden of disease, especially infectious diseases such as pneumonia, meningitis,
      tuberculosis, hepatitis A and B, and gastrointestinal disease. Death rates of
      American Indian/Alaska Native infants between 1 month and 1 year were much higher
      than in the US population as a whole, largely because of these infectious
      diseases. The health care of American Indian/Alaska Native patients was
      transferred to the Department of Health, Education, and Welfare in 1955 and
      placed under the administration of an agency soon to be known as the Indian
      Health Service. The few early pediatricians in the Indian Health Service
      recognized the severity of the challenges facing American Indian/Alaska Native
      children and asked for help. The American Academy of Pediatrics responded by
      creating the Committee on Indian Health in 1965. In 1986 the Committee on Native
      American Child Health replaced the Committee on Indian Health. Through the
      involved activity of these committees, the American Academy of Pediatrics
      participated in and influenced Indian Health Service policies and services and,
      combined with improved transportation, sanitation, and access to vaccines and
      direct services, led to vast improvements in the health of American Indian/Alaska
      Native children. In 1965, American Indian/Alaska Native postneonatal mortality
      was more than 3 times that of the general population of the United States. It is
      still more than twice as high as in other races but has decreased 89% since 1965.
      Infectious diseases, which caused almost one fourth of all American Indian/Alaska
      Native child deaths in 1965, now cause <1%. The Indian Health Service and tribal
      health programs, authorized by the Indian Self-Determination and Education
      Assistance Act of 1976 (Pub L. 93-638), continue to seek American Academy of
      Pediatrics review and assistance through the Committee on Native American Child
      Health to find and implement interventions for emerging child health problems
      related to pervasive poverty of many American Indian/Alaska Native communities.
      Acute infectious diseases that once were responsible for excess morbidity and
      mortality now are replaced by excess rates resulting from harmful behaviors,
      substance use, obesity, and injuries (unintentional and intentional). Through
      strong working partnerships such as that of the American Academy of Pediatrics
      and the Indian Health Service, progress hopefully will occur to address this "new
      morbidity." In this article we document the history of the Indian Health Service
      and the American Academy of Pediatrics committees that have worked with it and
      present certain statistics related to American Indian/Alaska Native child health
      that show the severity of the health-status disparities challenging American
      Indian/Alaska Native children and youth.

PMID- 17015515
TI  - The toothbrush: a rare but potentially life-threatening cause of penetrating
      oropharyngeal trauma in children.
AB  - We present the case of a 10-year-old girl with pharyngeal injury caused by a
      toothbrush, the snapped head of which lodged in her upper oropharyngeal wall.
      Initial examination of the oral cavity did not reveal bleeding, a foreign body,
      or a wound. Nasopharyngoscopy showed lodgment of the toothbrush piece in the
      upper oropharynx, pulsating in synchrony with heartbeats. Computed tomography
      showed the toothbrush head near the carotid artery. The foreign body was
      surgically removed without any intraoperative or postoperative complications. The
      diagnosis and management of oropharyngeal injuries by stick-like foreign bodies,
      such as a toothbrush or chopsticks, are discussed.

PMID- 17015516
TI  - Drowning in a sea of advice: pediatricians and American Academy of Pediatrics
      policy statements.
AB  - OBJECTIVE: The proliferation of policy statements from the American Academy of
      Pediatrics presents pediatricians with an increasing amount of health advice to
      deliver, yet no quantitative estimates of pediatric health advice expectations
      exist in the literature. The objective of this study was to quantify and
      characterize verbal health advice that pediatricians are expected to deliver to
      patients/guardians. METHODS: The authors read and coded the 344 American Academy
      of Pediatrics policy statements that are contained in the American Academy of
      Pediatrics' Pediatric Clinical Practice Guidelines and Policies, Third Edition,
      and identified 57 policies that contained health advice directives that are
      broadly relevant to pediatric practice. We extracted the individual advice text
      to a database in which we also coded its date of issue, its theme, and whether
      (1) it was duplicated in another policy, (2) a screening question was required to
      identify a target population for the advice, (3) handouts or other aids to
      delivering the advice were referenced in the policy itself, or (4) the text of
      the statement referred to evidence of the effectiveness of office-based delivery
      of the advice. RESULTS: These 57 policies were found to contain 192 discrete
      health advice directives that pediatricians are expected to deliver to
      patients/guardians. Seven (4%) of these directives originated before 1993, and
      185 (96%) were created from 1993 to 2002. After removal of the 30 (16%)
      duplicates, safety advice composed 67%, media use composed 12%, substance abuse
      composed 5%, environmental health hazards composed 4%, development/emotional
      health composed 4%, sexuality and pregnancy composed 3%, nutrition composed 2%,
      and miscellaneous composed 3%. In 41% of the directives, a screening question was
      required to identify the target population for the advice. Aids to delivering
      advice were referenced in 20% of the policies. In no policy statements did the
      text refer to evidence that office-based counseling was an effective method to
      achieve the desired health or behavioral outcome. CONCLUSIONS: We examined the
      American Academy of Pediatrics policy statements and found 162 different verbal
      health advice directives on which pediatricians should counsel parents and
      patients throughout childhood. The expectation that delivery of all of this
      advice can be achieved is unrealistic. Moreover, none of the reviewed statements
      were found to include an evidence-based discussion of the efficacy of the
      suggested advice. In light of these findings, we suggest that committees should
      consider both the feasibility and the evidence of efficacy of office-based health
      advice when generating future policy statements.

PMID- 17015517
TI  - Multicenter surveillance of invasive meningococcal infections in children.
AB  - OBJECTIVES: Meningococcal disease continues to result in substantial morbidity
      and mortality in children, but there is limited recent surveillance information
      regarding serogroup distribution and outcome in children in the United States.
      The objective of this study was to collect demographic, clinical, laboratory, and
      outcome information for infants and children who had Neisseria meningitidis
      infections of various serogroups and were cared for in 10 pediatric hospitals.
      METHODS: Investigators at each of the participating hospitals identified children
      with meningococcal infections and collected demographic and clinical information
      using a standard data form. Meningococcal isolates were sent to a central
      laboratory for serogrouping by slide agglutination and penicillin susceptibility.
      RESULTS: From January 1, 2001, through March 15, 2005, 159 episodes of systemic
      meningococcal infections were detected. The greatest numbers of children were
      younger than 12 months (n = 41) or were 12 to 24 months of age (n = 22).
      Meningitis was the most common clinical manifestation of disease accounting for
      112 (70%) cases; 43 (27%) children had bacteremia only. Children who were younger
      than 5 years (17 of 102) were significantly less likely to require mechanical
      ventilation than children who were 5 to 10 years of age (12 of 24) or children
      who were older than 10 years (13 of 33). Overall, 55 (44%) isolates were
      serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1
      isolate (intermediate) were susceptible to penicillin. The overall mortality rate
      was 8% (13 of 159) but was greater for children who were > or = 11 years of age
      (7 [21.2%] of 33) than for children who were younger than 11 years (6 [4.8%] of
      126). Unilateral or bilateral hearing loss occurred in 14 (12.5%) of 112 children
      with meningitis. CONCLUSIONS: The morbidity and the mortality of meningococcal
      infections are substantial. With the recent licensure of meningococcal conjugate
      vaccines, our baseline trends in meningococcal disease can be compared with those
      seen after widespread vaccination to assess the success of routine immunization.

PMID- 17015518
TI  - Clinical and education workload measurements using personal digital assistant
      based software.
AB  - OBJECTIVE: There are no accepted and practical measures of the relative clinical
      and educational activities of pediatricians who work in an academic health
      science center. Such measures are necessary for justification of existing and
      future human resource plans and evaluation of the activities and performance of
      physicians. The limited literature on the measurement of physician workload
      usually focuses on a specific subspecialty group and does not account for such
      issues as indirect patient care, such as telephone calls or e-mail consultations;
      variables that affect the delivery of clinical care, including patient acuity and
      complexity; and the presence of students during the patient care activities.
      After completing a pilot study that assessed the educational workload of faculty
      members, we adapted existing personal digital assistant technology and software
      to document clinical and educational activities. METHODS: Twenty full-time
      physicians from 4 subspecialty pediatric divisions participated in a 2-week
      evaluation project in May through June 2005. Clinical activities, with and
      without trainees, and educational activities were collected with the use of
      personal digital assistants. Software allowed an individualized division-specific
      drop-down menu. Information that was collected included clinical (location of
      activity, diagnosis, and time requirement) and educational activities. After
      completion of a 2-week data collection period, each physician was asked to
      complete a 5-question evaluation form. RESULTS: The project was completed
      successfully with capture of additional clinical and educational activities. A 5
      question evaluation form was completed by 70% of the participants at the end of
      the 2-week data collection. Data on clinical and educational activities were
      analyzed qualitatively and graphed. CONCLUSIONS: This method of workload data
      collection added significant information in capturing activities that are not
      measured in traditional workload evaluations for either clinical activities, such
      as e-mail, telephone, and patient information review, or educational endeavors,
      including mentoring and educational lectures and presentations.

PMID- 17015519
TI  - Assessing postoperative pain in neonates: a multicenter observational study.
AB  - OBJECTIVE: A multicenter observational study was conducted to evaluate the
      practices of postoperative pain assessment and management in neonates to identify
      specific targets for improvement in clinical practice. METHODS: Ten participating
      NICUs collected data for the 72 hours after a surgical operation on 25
      consecutive neonates (N = 250), including demographics, principal diagnoses,
      operative procedure, other painful procedures, pain assessments, interventions
      (pharmacologic and nonpharmacologic), and adverse events in neonates who
      underwent minor and major surgery. Descriptive and logistic-regression analyses
      were performed by using SPSS and Stata. RESULTS: The neonates studied had a birth
      weight of 2.4 +/- 1.0 kg (mean +/- SD) and gestational age of 36 +/- 4.3 weeks;
      57% were male, and length of hospital stay was 23.5 +/- 30.0 days. Participating
      hospitals used 7 different numeric pain scales, with nursing pain assessments
      documented for 88% (n = 220) of the patients and physician pain assessments
      documented for 9% (n = 23) of the patients. Opioids (84% vs 60%) and
      benzodiazepines (24% vs 11%) were used more commonly after major surgery than
      minor surgery, and a small proportion (7% major surgery, 12% minor surgery)
      received no analgesia. Logistic-regression analyses showed that physician pain
      assessment was the only significant predictor of postsurgical analgesic use,
      whereas major surgery and postnatal age in days did not seem to contribute.
      Physician pain assessment was documented for 23 patients; 22 of these received
      postoperative analgesia. CONCLUSIONS: Documentation of postoperative pain
      assessment and management in neonates was extremely variable among the
      participating hospitals. Pain assessment by physicians must be emphasized, in
      addition to developing evidence-based guidelines for postoperative care and
      educating professional staff to improve postoperative pain control in neonates.

PMID- 17015520
TI  - Comparison of outcome measures for a traditional pediatric faculty service and
      nonfaculty hospitalist services in a community teaching hospital.
AB  - OBJECTIVE: Several studies have found decreased cost and length of stay for
      patients who are cared for by pediatric hospitalists compared with traditional
      faculty models. The objective of this study was to compare cost and length of
      stay between a faculty group and 2 separate hospitalist groups in a community
      teaching hospital. This study differs from previous ones in that both the
      traditional faculty and hospitalist models were in place simultaneously, and the
      traditional faculty group was employed by the hospital, whereas the hospitalist
      groups were in private practice. METHODS: A total of 1009 pediatric patients with
      any of the 11 most frequent diagnosis-related groups were analyzed according to
      the admitting physician group. Total direct costs and length of stay were
      computed for 3 separate groups (faculty group, hospitalist group 1, and
      hospitalist group 2). Linear regression models were used to compare total direct
      costs and length of stay among the groups. Each model accounted for age, severity
      index, and payer source. RESULTS: Age, severity index, and physician group were
      predictive in determining total direct costs and length of stay. There was no
      significant difference in patient age among the groups, but the faculty group had
      significantly increased severity indices compared with hospitalist groups 1 and 2
      (1.6 +/- 0.7 vs 1.3 +/- 0.6 vs 1.4 +/- 0.6, mean +/- SD). The faculty group had
      statistically significantly lower total direct costs compared with hospitalist
      groups 1 and 2 (1781 dollars +/- 1449 dollars vs 1954 dollars +/- 1212 dollars vs
      1964 dollars +/- 1495 dollars, mean +/- SD). The faculty group had shorter
      average length of stay compared with hospitalist groups 1 and 2 (2.6 +/- 2.0 vs
      3.1 +/- 2.6 vs 2.9 +/- 2.3, mean +/- SD). The readmission rates among the groups
      were similar. CONCLUSIONS: Traditional faculty models can be as efficient in
      terms of total direct costs and length of stay as evolving hospitalist models.
      This study's results may be unique because the traditional faculty model was
      composed of general pediatricians instead of a blend of generalists and
      subspecialists. In addition, the traditional faculty physicians concentrated
      almost entirely on the care of inpatients while engaged in hospital care.

PMID- 17015521
TI  - Adverse events in the neonatal intensive care unit: development, testing, and
      findings of an NICU-focused trigger tool to identify harm in North American
      NICUs.
AB  - OBJECTIVES: Currently there are few practical methods to identify and measure
      harm to hospitalized children. Patients in NICUs are at high risk and warrant a
      detailed assessment of harm to guide patient safety efforts. The purpose of this
      work was to develop a NICU-focused tool for adverse event detection and to
      describe the incidence of adverse events in NICUs identified by this tool.
      METHODS: A NICU-focused trigger tool for adverse event detection was developed
      and tested. Fifty patients from each site with a minimum 2-day NICU stay were
      randomly selected. All adverse events identified using the trigger tool were
      evaluated for severity, preventability, ability to mitigate, ability to identify
      the event earlier, and presence of associated occurrence report. Each trigger,
      and the entire tool, was evaluated for positive predictive value. Study chart
      reviewers, in aggregate, identified 88.0% of all potential triggers and 92.4% of
      all potential adverse events. RESULTS: Review of 749 randomly selected charts
      from 15 NICUs revealed 2218 triggers or 2.96 per patient, and 554 unique adverse
      events or 0.74 per patient. The positive predictive value of the trigger tool was
      0.38. Adverse event rates were higher for patients <28 weeks' gestation and <1500
      g birth weight. Fifty-six percent of all adverse events were deemed preventable;
      16% could have been identified earlier, and 6% could have been mitigated more
      effectively. Only 8% of adverse events were identified in existing hospital-based
      occurrence reports. The most common adverse events identified were nosocomial
      infections, catheter infiltrates, and abnormal cranial imaging. CONCLUSIONS:
      Adverse event rates in the NICU setting are substantially higher than previously
      described. Many adverse events resulted in permanent harm and the majority were
      classified as preventable. Only 8% were identified using traditional voluntary
      reporting methods. Our NICU-focused trigger tool appears efficient and effective
      at identifying adverse events.

PMID- 17015522
TI  - Determinants and impact of generalist-specialist communication about pediatric
      outpatient referrals.
AB  - OBJECTIVE: Effective communication between primary care and specialty physicians
      is essential for comanagement when children are referred to specialty care. We
      sought to determine rates of physician-reported communication between primary
      care physicians and specialists, the clinical impact of communication or its
      absence, and patient- and practice system-level determinants of communication for
      a cohort of children referred to specialty care. METHODS: We enrolled 179
      patients newly referred from general pediatricians in 30 community practices to
      15 pediatric medical specialists in 5 specialties. Primary care physicians and
      specialists completed questionnaires at the first specialty visit and 6 months
      later. Questions covered communication received by primary care physicians and
      specialists, its impact on care provision, system characteristics of practices,
      and roles of physicians in treatment. We used multivariate logistic regression to
      determine associations between practice system and patient characteristics and
      the dependent variable of reported primary care physician-specialist
      communication. RESULTS: Specialists reported communication from referring primary
      care physicians for only 50% of initial referrals, whereas primary care
      physicians reported communication from specialists after 84% of initial
      consultations. Communication was strongly associated with physicians' reported
      ability to provide optimal care. System characteristics associated with reported
      primary care physician-specialist communication were computer access to chart
      notes and lack of delays in receipt of information. Associated patient
      characteristics included non-Medicaid insurance, no additional specialists seen,
      and specialty to which referred. Physicians favored comanagement of referred
      patients in more than two thirds of the cases. CONCLUSIONS: Although a
      prerequisite for optimal care, communication from primary care physicians to
      specialists is frequently absent. Interventions should promote widely accessible
      clinical information systems and target children with complex needs and public
      insurance.

PMID- 17015523
TI  - Does cause of deafness influence outcome after cochlear implantation in children?
AB  - OBJECTIVES: The objective of this study was to evaluate long-term speech
      perception abilities of comparable groups of postmeningitic and congenitally deaf
      children after cochlear implantation. METHODS: This prospective longitudinal
      study comprised 46 postmeningitic deaf children and 83 congenitally deaf children
      with age at implantation of < or = 5.6 years. Both groups were comparable with
      respect to educational setting and mode of communication and included children
      with additional disabilities. RESULTS: Both postmeningitic and congenitally deaf
      children showed significant progress after implantation. Most (73% and 77%,
      respectively) could understand conversation without lip-reading or use the
      telephone with a known speaker 5 years after implantation, whereas none could do
      so before implantation. At the same interval, the postmeningitic and congenitally
      deaf children scored a mean open-set speech perception score of 47 (range: 0-91)
      and 46 (range: 0-107) words per minute, respectively, on connected discourse
      tracking. The respective mean scores at the 3-year interval were 22 and 29
      correct words per minute, respectively. None of these children could score a
      single correct word per minute before implantation. The progress in both groups
      was statistically significant. When the 2 groups were compared, there was no
      statistically significant difference. CONCLUSION: Postmeningitic and congenitally
      deaf children showed significant improvement in their auditory receptive
      abilities at the 3- and 5-year intervals after cochlear implantation. There was
      no statistically significant difference between the outcomes of the 2 groups,
      suggesting that, provided that children receive an implant early, cause of
      deafness has little influence on outcome. Although the prevalence of other
      disabilities was similar in both groups, for individual children, their presence
      may have profound impact. The study supports the concept of implantation early in
      life, irrespective of the cause of deafness.

PMID- 17015524
TI  - Primary care physicians' knowledge, attitudes, and practices related to newborn
      hearing screening.
AB  - OBJECTIVE: Universal newborn hearing screening focuses on providing the earliest
      possible diagnosis for infants with permanent hearing loss. The goal is to
      prevent or minimize the consequences of sensorineural hearing loss on speech and
      language development through timely and effective diagnosis and interventions.
      Pediatricians are in a key position to educate families about the importance of
      follow-up, if they are well informed. The objective of this study was to survey
      the attitudes, practices, and knowledge of primary care physicians in relation to
      newborn hearing screening and follow-up. METHODS: A survey was created on the
      basis of input from focus groups with primary care physicians. Surveys (n =
      12,211) were sent to primary care physicians in 21 states and 1 territory (Puerto
      Rico) regarding practices, knowledge, and attitudes related to universal newborn
      hearing screening. The response rate was 16.1% (n = 1968). RESULTS: Physicians
      reported a high level of support for universal newborn hearing screening; 81.6%
      judged it to be very important to screen all newborns for hearing loss at birth.
      Although physicians reported confidence in talking with parents about screening
      results, they indicated a lack of confidence in discussing follow-up procedures
      and intervention needs. Several important gaps in knowledge were identified, and
      these represent priorities for education, as based on their relevance to medical
      management and parent support. Physicians expressed a strong preference for
      action-oriented resources. CONCLUSION: Pediatricians and other primary care
      providers recognize the benefits of early detection and intervention for
      permanent hearing loss in infants. The current system of newborn hearing
      screening can be enhanced by strengthening the medical community's involvement in
      the process from screening to follow-up. Physician roles will be supported
      through the provision of action-oriented resources that educate parents about the
      importance of follow-up and that prepare professionals to incorporate appropriate
      surveillance procedures in daily practice.

PMID- 17015525
TI  - Evaluation of resident communication skills and professionalism: a matter of
      perspective?
AB  - OBJECTIVE: Evaluation procedures that rely solely on attending physician ratings
      may not identify residents who display poor communication skills or
      unprofessional behavior. Inclusion of non-physician evaluators should capture a
      more complete account of resident competency. No published reports have examined
      the relationship between resident evaluations obtained from different sources in
      pediatric settings. The objective of this study was to determine whether parent
      and nurse ratings of specific resident behaviors significantly differ from those
      of attending physicians. METHODS: Thirty-six pediatric residents were evaluated
      by parents, nurses, and attending physicians during their first year of training.
      For analysis, the percentage of responses in the highest response category was
      calculated for each resident on each item. Differences between attending
      physician ratings and those of parents and nurses were compared using the signed
      rank test. RESULTS: Parent and attending physician ratings were similar on most
      items, but attending physicians indicated that they frequently were unable to
      observe the behaviors of interest. Nurses rated residents lower than did
      attending physicians on items that related to respecting staff (69% vs 97%),
      accepting suggestions (56% vs 82%), teamwork (63% vs 88%), being sensitive and
      empathetic (62% vs 85%), respecting confidentiality (73% vs 97%), demonstrating
      integrity (75% vs 92%), and demonstrating accountability (67% vs 83%). Nurse
      responses were higher than attending physicians on anticipating postdischarge
      needs (46% vs 25%) and effectively planning care (52% vs 33%). CONCLUSIONS:
      Expanding resident evaluation procedures to include parents and nurses does
      enhance information that is gathered on resident communication skills and
      professionalism and may help to target specific behaviors for improvement.
      Additional research is needed to determine whether receiving feedback on parent
      and nurse evaluations will have a positive impact on resident competency.

PMID- 17015526
TI  - Evaluation of the Clinical Assessment project: a computer-based multimedia tool
      to assess problem-solving ability in medical students.
AB  - OBJECTIVE: The purpose of this work was to describe Clinical Assessment, a
      computer-based multimedia patient simulation used to assess the problem-solving
      abilities of medical students and to evaluate its capacity to guide the
      assignment of course grade. METHODS: This was a multisite reviewer-blinded
      comparison of course grades, National Board of Medical Examiners pediatric
      examination score, and Clinical Assessment scores at 3 pediatric clerkship sites
      of the Harvard Medical School. Participants included 470 students completing
      their pediatric clerkships. Each student's performance on < or = 4 Clinical
      Assessment patient case simulations was compared with National Board of Medical
      Examiners pediatric examination scores and course grades assigned by clerkship
      directors based on overall ward performance. RESULTS: Data from both the National
      Board of Medical Examiners pediatric "shelf" examination and the course grade
      were available for 411 students who completed > or = 1 Clinical Assessment case.
      There was a strong correlation between Clinical Assessment score and course grade
      when comparing students receiving honors versus satisfactory category course
      grades. Students who ordered more expensive or greater numbers of laboratory
      tests did not achieve greater diagnostic accuracy on Clinical Assessment.
      Clinical Assessment had a high positive predictive value for course grade: 95% of
      students scoring > or = 90% on Clinical Assessment achieved an honors category
      course grade. CONCLUSIONS: Because nearly all of the students who scored very
      well on Clinical Assessment received honors category course grades, future high
      scorers on this examination merit consideration for assigning a high course
      grade. A computer-based multimedia patient simulation assessment tool provides
      objective information that can complement a student's National Board of Medical
      Examiners score and course grade and may assist in evaluating clinical problem
      solving ability.

PMID- 17015527
TI  - Prevalence of fatty liver in children and adolescents.
AB  - OBJECTIVE: Fatty liver disease is diagnosed increasingly in children, but the
      prevalence remains unknown. We sought to determine the prevalence of pediatric
      fatty liver as diagnosed by histology in a population-based sample. METHODS: We
      conducted a retrospective review of 742 children between the ages of 2 and 19
      years who had an autopsy performed by a county medical examiner from 1993 to
      2003. Fatty liver was defined as > or = 5% of hepatocytes containing
      macrovesicular fat. RESULTS: Fatty liver was present in 13% of subjects. For
      children and adolescents age 2 to 19 years, the prevalence of fatty liver
      adjusted for age, gender, race, and ethnicity is estimated to be 9.6%. Fatty
      liver prevalence increases with age, ranging from 0.7% for ages 2 to 4 up to
      17.3% for ages 15 to 19 years. Fatty liver prevalence differs significantly by
      race and ethnicity (Asian: 10.2%; black: 1.5%; Hispanic: 11.8%; white: 8.6%). The
      highest rate of fatty liver was seen in obese children (38%). CONCLUSIONS: Fatty
      liver is the most common liver abnormality in children age 2 to 19 years. The
      presence of macrovesicular hepatic steatosis in approximately 1 of every 10
      children has important ramifications for the long-term health of children and
      young adults. The influence of the risk factors identified should be taken into
      consideration in the development of protocols designed to screen at-risk children
      and adolescents.

PMID- 17015528
TI  - The impact of conjugate pneumococcal vaccination on routine childhood vaccination
      and primary care use in 2 counties.
AB  - BACKGROUND: Pneumococcal conjugate vaccine immunization recommendations were
      rapidly implemented by primary care providers. Before the recommendations,
      concern was expressed that adding pneumococcal conjugate vaccine might result in
      delays in other vaccinations or preventive services. OBJECTIVES: The study
      objectives were to measure whether incorporation of pneumococcal conjugate
      vaccine by primary care providers delayed other vaccinations or added primary
      health care visits. DESIGN AND METHODS: In 2 counties surrounding Rochester and
      Nashville, we reviewed a representative sample of primary care charts for
      children born before and after licensure of pneumococcal conjugate vaccine.
      Receipt of vaccinations and health care visits were compared for the 2 age
      matched cohorts. RESULTS: We reviewed 1459 records from Rochester and 1857
      records from Nashville. The pre-pneumococcal conjugate vaccine and post
      pneumococcal conjugate vaccine cohorts had similar demographic characteristics.
      The median age for receipt of any vaccination was not older for the postvaccine
      cohort than for the prevaccine cohort in either community. The percentage of
      children up-to-date for vaccinations by 18 months for postvaccine versus
      prevaccine cohorts was similar in Rochester (72% in each cohort) and in Nashville
      (58% postvaccine and 65% prevaccine). The number of well-child care visits or
      other health care visits during the first 18 months of life was not statistically
      different between the 2 cohorts. CONCLUSIONS: Implementation of pneumococcal
      conjugate vaccine was not associated with delays in other childhood vaccinations
      or more primary care visits.

PMID- 17015529
TI  - Near elimination of hepatitis B virus infections among Hawaii elementary school
      children after universal infant hepatitis B vaccination.
AB  - OBJECTIVES: Hawaii implemented routine infant hepatitis B vaccination in 1992 and
      required it for school entry in 1997. Previously, in 1989, a serologic survey
      among Hawaii school children in grades 1 to 3 indicated that 1.6% had chronic
      hepatitis B virus infection, and 2.1% had resolved infection. We conducted a
      follow-up survey to examine changes in hepatitis B virus infection rates.
      PATIENTS AND METHODS: This study was performed in Oahu, Hawaii, during the 2001
      2002 school year among children in grades 2 and 3. Consenting parents/guardians
      provided demographic information including place of birth. Participants were
      tested for serologic evidence of hepatitis B virus infection and their
      vaccination status was determined by reviewing school records. Rates of
      symptomatic acute hepatitis B among persons aged < or = 19 years were calculated
      from cases reported from Hawaii to the Centers for Disease Control and Prevention
      between 1990 and 2004. RESULTS: Completed hepatitis B vaccination series were
      documented for 83% of the 2469 participants by age 18 months and for 97% by age 5
      years. Past or present hepatitis B virus infection was detected among 6
      participants (0.24%), including 1 (0.04%) with chronic infection and 5 (0.20%)
      with resolved infections. Compared with the 1989 survey, these prevalences
      represent declines of 97% and 90% in chronic and resolved hepatitis B virus
      infections, respectively. The incidence of symptomatic acute hepatitis B in
      Hawaii children and adolescents aged < or = 19 years decreased from 4.5 cases per
      100,000 in 1990 to 0.0 during 2002-2004. To date, the last reported case in a
      child aged < 15 years in Hawaii occurred in 1996. CONCLUSIONS: Hepatitis B virus
      infection has nearly been eliminated in Hawaii children born after universal
      infant hepatitis B vaccination was implemented. These findings suggest that
      hepatitis B prevention goals are being met through routine immunization and
      related prevention programs among US children.

PMID- 17015530
TI  - Randomized, controlled trial comparing synchronized intermittent mandatory
      ventilation and synchronized intermittent mandatory ventilation plus pressure
      support in preterm infants.
AB  - BACKGROUND: Prolonged mechanical ventilation is associated with lung injury in
      preterm infants. In these infants, weaning from synchronized intermittent
      mandatory ventilation may be delayed by their inability to cope with increased
      respiratory loads. The addition of pressure support to synchronized intermittent
      mandatory ventilation can offset these loads and may facilitate weaning.
      OBJECTIVE: The purpose of this work was to compare synchronized intermittent
      mandatory ventilation and synchronized intermittent mandatory ventilation plus
      pressure support in weaning from mechanical ventilation and the duration of
      supplemental oxygen dependency in preterm infants with respiratory failure.
      METHODS: Preterm infants weighing 500 to 1000 g at birth who required mechanical
      ventilation during the first postnatal week were randomly assigned to
      synchronized intermittent mandatory ventilation or synchronized intermittent
      mandatory ventilation plus pressure support. In both groups, weaning followed a
      set protocol during the first 28 days. Outcomes were assessed during the first 28
      days and until discharge or death. RESULTS: There were 107 infants enrolled (53
      synchronized intermittent mandatory ventilation plus pressure support and 54
      synchronized intermittent mandatory ventilation). Demographic and perinatal data,
      mortality, and morbidity did not differ between groups. During the first 28 days,
      infants in the synchronized intermittent mandatory ventilation plus pressure
      support group reached minimal ventilator settings and were extubated earlier than
      infants in the synchronized intermittent mandatory ventilation group. Total
      duration of mechanical ventilation, duration of oxygen dependency, and oxygen
      need at 36 weeks' postmenstrual age alone or combined with death did not differ
      between groups. However, infants in synchronized intermittent mandatory
      ventilation plus pressure support within the 700- to 1000-g birth weight strata
      had a shorter oxygen dependency. CONCLUSIONS: The results of this study suggest
      that the addition of pressure support as a supplement to synchronized
      intermittent mandatory ventilation during the first 28 days may play a role in
      reducing the duration of mechanical ventilation in extremely low birth-weight
      infants, and it may lead to a reduced oxygen dependency in the 700- to 1000-g
      birth weight strata.

PMID- 17015531
TI  - Changing epidemiology of life-threatening upper airway infections: the
      reemergence of bacterial tracheitis.
AB  - OBJECTIVE: As a consequence of evolving medical practice, the epidemiology of
      potentially life-threatening upper airway infections is changing. We report our
      experience over 9 years with viral croup, epiglottitis, and bacterial tracheitis.
      PATIENTS AND METHODS: We studied a retrospective case series of patients admitted
      to Vermont Children's Hospital with potentially life-threatening upper airway
      infections viral croup, epiglottitis, or bacterial tracheitis between 1997 and
      2006. MEASUREMENT AND MAIN RESULTS: There were 107 patients with viral croup
      admitted to Vermont Children's Hospital, with 16 (15%) admitted to the pediatric
      intensive care unit. Three patients with croup (17% of pediatric intensive care
      unit admissions, 3% of total admissions) required intubation. There were no
      serious complications. Eighteen patients were admitted with bacterial tracheitis.
      Ninety-four percent (n = 17) were admitted to the pediatric intensive care unit.
      Eighty-three percent (n = 15) were intubated. Twenty-eight percent of patients (n
      = 5) developed serious complications. Two adolescent patients were admitted with
      epiglottitis. Both were intubated and recovered without complications. Of 35
      patients admitted to the pediatric intensive care unit with these potentially
      life-threatening upper airway infections, 20 patients (57%) developed respiratory
      failure. Fifteen patients (75%) had bacterial tracheitis, 3 patients (15%) had
      viral croup, and 2 patients (10%) had nonclassic epiglottitis. CONCLUSIONS:
      Immunization against Haemophilus influenza type b and widespread use of
      corticosteroids for the treatment of viral croup have changed the epidemiology of
      acute infectious upper airway disease. As potentially life-threatening
      infections, viral croup and epiglottitis have been eclipsed by bacterial
      tracheitis. In this series, bacterial tracheitis was 3 times more likely to have
      caused respiratory failure than viral croup and epiglottitis combined. Bacterial
      tracheitis should be considered in children who present with acute life
      threatening upper airway infection.

PMID- 17015532
TI  - Evaluation of potentially common adverse events associated with the first and
      second doses of measles-mumps-rubella vaccine.
AB  - BACKGROUND/OBJECTIVES: In 1989, the American Academy of Pediatrics and the
      Advisory Committee on Immunization Practices recommended that school children
      receive 2 doses of measles-mumps-rubella vaccine. With measles and rubella
      eliminated from the United States, measles-mumps-rubella vaccine adverse events
      have come under scrutiny, but no study has compared the reactogenicity of the
      first (measles-mumps-rubella vaccine dose 1) and second (measles-mumps-rubella
      vaccine dose 2) doses at the most common ages of administration in the United
      States. METHODS: From a health maintenance organization, 3 groups of children
      were recruited: (1) toddlers aged 12 to 24 months receiving measles-mumps-rubella
      vaccine dose 1; (2) kindergartners aged 4 to 6 years receiving measles-mumps
      rubella vaccine dose 2; and (3) middle schoolers aged 10 to 12 years receiving
      measles-mumps-rubella vaccine dose 2. From 2 weeks before measles-mumps-rubella
      vaccine administration until 4 weeks afterward, families recorded in diaries the
      occurrence of potentially common symptoms. Postvaccination symptom rates were
      compared with the prevaccination baseline, with significance assessed by testing
      incidence rate ratios estimated by Poisson regression. RESULTS: Of 2173 children
      enrolled, 373 (17%) were lost to attrition, producing a study population of 1800.
      Compared with the prevaccination baseline, rates of fever, diarrhea, and rash
      were significantly elevated postvaccination among 535 toddlers receiving measles
      mumps-rubella vaccine dose 1. An estimated net 95 (18%) experienced measles-mumps
      rubella vaccine-associated events (median onset 5-10 days postvaccination,
      duration 2-5 days), with high fever (temperature > or = 39.5 degrees C) occurring
      in 33 (6%). None required medical attention. For 633 kindergartners and 632
      middle schoolers, symptom rates were not significantly elevated after measles
      mumps-rubella vaccine dose 2 compared with baseline. CONCLUSIONS: Vaccination
      associated adverse events occur in approximately 1 of every 6 toddlers receiving
      measles-mumps-rubella vaccine dose 1, with high fever occurring in 1 of 20.
      Adverse events are infrequent for measles-mumps-rubella vaccine dose 2
      administered to school-aged children.

PMID- 17015533
TI  - Incorporating vaccine-preventable disease surveillance into the National Health
      Information Network: leveraging children's hospitals.
AB  - OBJECTIVE: Development of national biosurveillance systems to advance regional
      and national data exchange among sites of clinical care and public health
      authorities is a top federal priority, creating the opportunity to develop a
      unified national network for tracking and responding to cases of vaccine
      preventable diseases. The purpose of this study was to assess the current
      practice and feasibility of developing a nationwide network of children's
      hospitals to conduct surveillance for vaccine preventable diseases. METHODS: In
      2004-2005, Web-based surveys were sent to 506 key hospital personnel from 119
      pediatric hospitals, identified by the National Association of Children's
      Hospitals and Related Institutions. Surveys measured attitudes toward public
      health initiatives, willingness to join a surveillance network of children's
      hospitals, knowledge of mandated reporting requirements, methods of disease
      detection and reporting, and data sources available for surveillance. RESULTS: A
      total of 395 (78%) respondents from 119 hospitals completed the survey.
      Surveillance at pediatric hospitals is largely passive and driven by unreimbursed
      efforts of infection control staff. It is vulnerable to missing cases that occur
      in the outpatient setting and are diagnosed clinically without laboratory
      confirmation or are never diagnosed by clinicians. Nearly 90% of hospital leaders
      are interested in participating in public health programs, and most are
      interested in a national network to conduct active surveillance for vaccine
      preventable diseases, dependent on the provision of sufficient funding. Pediatric
      hospitals store records relevant to surveillance in an electronic fashion
      accessible to query, but <20% of these hospitals use automated methods to report
      cases of disease. CONCLUSIONS: There is both the will and capability to create a
      robust active pediatric hospital-based reporting system for vaccine preventable
      diseases. This effort would dovetail well with the national priority to bolster
      surveillance, as well as with the goal of reducing morbidity and mortality from
      vaccine-preventable diseases.

PMID- 17015534
TI  - Population-based study of the impact of childcare attendance on hospitalizations
      for acute respiratory infections.
AB  - OBJECTIVES: It is well known that children attending childcare have a higher risk
      of acute respiratory infections compared with children in home care; however,
      knowledge is sparse regarding how the excess risk of acute respiratory infection
      varies with age, time since enrollment, and other factors. METHODS: A national
      register-based study of 138,821 inpatient admissions to hospital for acute
      respiratory infection during 3,982,925 person-years of follow-up in Danish
      children aged 0 to 5 years. Data on child and family characteristics, childcare
      attendance, and hospitalizations were obtained from Danish registries. The
      outcome of the study was inpatient admissions to hospital for acute respiratory
      infection. Incidence rate ratios were estimated using Poisson regression.
      RESULTS: In children < 1 year of age, the first 6 months of enrollment in the
      first childcare facility were associated with a 69% higher incidence of
      hospitalizations for acute respiratory infection compared with children in home
      care. Similar figures for children aged 1, 2, and > or = 3 years were 47%, 41%,
      and 8%, respectively. The incidence decreased after the first 6 months, and after
      > or = 1 year in childcare the incidence was comparable with that of children in
      home care. Similar patterns were seen after second enrollment. For 0- to 2-year
      old children living in households with no additional children < 5 years, the
      excess incidence during the first 6 months of enrollment was 100% compared with
      25% and 9% for children living with 1 and > or = 2 additional children,
      respectively. CONCLUSIONS: The increased risk of acute respiratory infection was
      most pronounced among 0- to 2-year-old children living with no other children
      during the first 6 months of enrollment. Our findings may suggest that it would
      be optimal to postpone enrollment into childcare until after 1 year of age.

PMID- 17015535
TI  - Pathobiological determinants of atherosclerosis in youth risk scores are
      associated with early and advanced atherosclerosis.
AB  - OBJECTIVES: Atherosclerosis begins in childhood and progresses during adolescence
      and young adulthood. The Pathobiological Determinants of Atherosclerosis in Youth
      Study previously reported risk scores to estimate the probability of advanced
      atherosclerotic lesions in young individuals aged 15 to 34 years using the
      coronary heart disease risk factors (gender, age, serum lipoprotein
      concentrations, smoking, hypertension, obesity, and hyperglycemia). In this study
      we investigated the relation of these risk scores to the early atherosclerotic
      lesions. METHODS: We measured atherosclerotic lesions in the left anterior
      descending coronary artery, right coronary artery, and abdominal aorta and the
      coronary heart disease risk factors in persons 15 to 34 years of age who died as
      a result of external causes and were autopsied in forensic laboratories. RESULTS:
      Risk scores computed from the modifiable risk factors were associated with
      prevalence of microscopically demonstrable lesions of atherosclerosis (American
      Heart Association grade 1) in the left anterior descending coronary artery and
      with the extent of the earliest detectable gross lesion (fatty streaks) in the
      right coronary artery and abdominal aorta. Risk scores computed from the
      modifiable risk factors also were associated with prevalence of lesions of higher
      degrees of microscopic severity (intermediate as well as advanced) in the left
      anterior descending coronary artery and with extent of lesions of higher degrees
      of severity (intermediate and raised lesions) in the right coronary artery and
      abdominal aorta. CONCLUSIONS: Risk scores calculated from traditional coronary
      heart disease risk factors to identify individual young persons with high
      probability of having advanced atherosclerotic lesions also are associated with
      earlier atherosclerotic lesions, including the earliest anatomically demonstrable
      atherosclerotic lesion. These results support lifestyle modification in youth to
      prevent development of the initial lesions and the subsequent progression to
      advanced lesions and, thereafter, to prevent or delay coronary heart disease.

PMID- 17015536
TI  - Hemodynamic changes after low-dosage hydrocortisone administration in vasopressor
      treated preterm and term neonates.
AB  - OBJECTIVE: We sought to investigate whether the increase in blood pressure and
      decrease in vasopressor support after hydrocortisone administration are
      associated with changes in systemic hemodynamics in neonates who receive high
      dosage dopamine to maintain blood pressure at the lowest acceptable levels.
      METHODS: In this prospective, observational study, preterm and term neonates who
      required dopamine > or = 15 microg/kg per minute to maintain minimum acceptable
      blood pressure received intravenous hydrocortisone 2 mg/kg followed by up to 4
      doses of 1 mg/kg every 12 hours. Fifteen preterm and 5 term neonates without a
      patent ductus arteriosus composed the study population. Echocardiograms and
      vascular Doppler studies were performed immediately before the first dose of
      hydrocortisone and at 1, 2, 6 to 12, 24, and 48 hours thereafter. RESULTS: In the
      15 preterm infants, during the first 12 hours of hydrocortisone treatment, the
      28% increase in blood pressure paralleled that in the systemic vascular
      resistance without changes in stroke volume or cardiac output, whereas dopamine
      dosage decreased. By 24 hours, the dosage of dopamine continued to decrease,
      whereas stroke volume increased without additional changes in systemic vascular
      resistance. By 48 hours, dopamine dosage decreased by 72%; blood pressure and
      stroke volume increased by 31% and 33%, respectively; and systemic vascular
      resistance and cardiac output tended to be higher (14% and 21%, respectively)
      compared with baseline. Contractility, global myocardial function, and Doppler
      indices of blood flow in the middle cerebral and renal artery remained normal and
      unchanged. The findings in the 5 term infants showed a similar pattern for
      changes in cardiac function, systemic hemodynamics, and organ blood flow after
      hydrocortisone administration. CONCLUSIONS: In preterm and term neonates who
      require high-dosage dopamine to maintain blood pressure at the lowest acceptable
      levels, hydrocortisone improves blood pressure without compromising cardiac
      function, systemic perfusion, or cerebral and renal blood flow.

PMID- 17015537
TI  - Comparative prognostic utilities of early quantitative magnetic resonance imaging
      spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal
      encephalopathy.
AB  - OBJECTIVE: We sought to compare the prognostic utilities of early MRI spin-spin
      relaxometry and proton magnetic resonance spectroscopy in neonatal
      encephalopathy. METHODS: Twenty-one term infants with neonatal encephalopathy
      were studied at a mean age of 3.1 days (range: 1-5). Basal ganglia, thalamic and
      frontal, parietal, and occipital white matter spin-spin relaxation times were
      determined from images with echo times of 25 and 200 milliseconds. Metabolite
      ratios were determined from an 8-mL thalamic-region magnetic resonance
      spectroscopy voxel (1H point-resolved spectroscopy; echo time 270 milliseconds).
      Outcomes were assigned at age 1 year as follows: (1) normal, (2) moderate
      (neuromotor signs or Griffiths developmental quotient of 75-84), (3) severe
      (functional neuromotor deficit or developmental quotient <75 or died). Predictive
      efficacies for differentiation between normal and adverse (combined moderate and
      severe) outcomes were compared by receiver operating characteristic curve
      analysis and logistic regression. RESULTS: Thalamic and basal ganglia spin-spin
      relaxation times correlated positively with outcome and predicted adversity.
      Although thalamic and basal ganglia spin-spin relaxation times were prognostic of
      adversity, magnetic resonance spectroscopy metabolite ratios were better
      predictors, and, of these, lactate/N-acetylaspartate was most accurate.
      CONCLUSIONS: Deep gray matter spin-spin relaxation time was increased in the
      first few days after birth in infants with an adverse outcome. Proton magnetic
      resonance spectroscopy was more prognostic than spin-spin relaxation time, with
      lactate/N-acetylaspartate the best measure. Nevertheless, both techniques were
      useful for early prognosis, and the potential superior spatial resolution of spin
      spin relaxometry may define better the precise anatomic pattern of injury in the
      early days after birth.

PMID- 17015538
TI  - Food-related advertising on preschool television: building brand recognition in
      young viewers.
AB  - OBJECTIVES: This study used content analysis to explore how much and what type of
      advertising is present in television programming aimed at toddlers and preschool
      aged children and what methods of persuasion are being used to sell products and
      to promote brands to the youngest viewers. METHODS: Four randomly selected, 4
      hour blocks (9 am to 1 pm) were recorded in spring 2005 from each of 3 stations
      airing programming aimed specifically at toddlers and preschool-aged children
      (Public Broadcasting Service, Disney, and Nickelodeon). All content that aired in
      the spaces between programs was examined. Data recorded for food-related
      advertisements included the primary appeals used to promote products or brands,
      whether advertisements were aimed at children or adults, whether advertisements
      used primarily animation or live action, whether advertisements showed food, and
      whether licensed characters were used. RESULTS: In 96 half-hour blocks of
      preschool programming, the 3 stations had a total of 130 food-related
      advertisements (1.354 food advertisements per half-hour). More than one half of
      all food advertisements (76 of 130 advertisements) were aimed specifically at
      children, and the majority of those were for fast food chains (50 advertisements)
      or sweetened cereals (18 advertisements). The primary advertising appeals used
      associated products with fun and happiness and/or with excitement and energy.
      Fast food advertisements in particular seemed to focus on building brand
      recognition and positive associations, through the use of licensed characters,
      logos, and slogans. CONCLUSIONS: The majority of child-oriented food
      advertisements viewed seemed to take a branding approach, focusing on creating
      lifelong customers rather than generating immediate sales. Promotional spots on
      advertisement-supported (Nickelodeon) and sponsor-supported (Public Broadcasting
      Service and Disney) networks took similar approaches and used similar appeals,
      seeming to promote the equation that food equals fun and happiness.

PMID- 17015539
TI  - The influence of head growth in fetal life, infancy, and childhood on
      intelligence at the ages of 4 and 8 years.
AB  - OBJECTIVE: We investigated the effects of head growth prenatally, during infancy,
      and during later periods of development on cognitive function at the ages of 4
      and 8 years. METHODS: We studied 633 term-born children from the Avon
      Longitudinal Study of Parents and Children cohort whose head circumference was
      measured at birth and at regular intervals thereafter. Their cognitive function
      was assessed with the Wechsler Preschool and Primary Scale of Intelligence at the
      age of 4 years and with the Wechsler Intelligence Scale for Children at the age
      of 8 years. Linear regression analysis was used to calculate postnatal head
      growth between successive time points, conditional on previous size, and to
      examine the relationship between head growth during different periods of
      development and later IQ. RESULTS: When the influence of head growth was
      distinguished for different periods, only prenatal growth and growth during
      infancy were associated with subsequent IQ. At 4 years, after adjustment for
      parental characteristics, full-scale IQ increased an average of 2.41 points for
      each 1-SD increase in head circumference at birth and 1.97 points for each 1-SD
      increase in head growth during infancy, conditional on head size at birth. At 8
      years, head circumference at birth was no longer associated with IQ, but head
      growth during infancy remained a significant predictor, with full-scale IQ
      increasing an average of 1.56 points for each 1-SD increase in growth.
      CONCLUSION: The brain volume a child achieves by the age of 1 year helps
      determine later intelligence. Growth in brain volume after infancy may not
      compensate for poorer earlier growth.

PMID- 17015540
TI  - Emergency medical services system changes reduce pediatric epinephrine dosing
      errors in the prehospital setting.
AB  - OBJECTIVE: The goal was to describe the change in the rate of epinephrine dosing
      errors in the treatment of pediatric patients in prehospital cardiopulmonary
      arrest after the Los Angeles County Emergency Medical Services Agency instituted
      a program in which paramedics were required to use the Broselow tape and to
      report color zone categories to the base station and base stations were given and
      instructed formally in the use of the color-coded drug dosing chart. METHODS: An
      observational analysis of a natural experiment was performed. Children < or = 12
      years of age who were determined to be in prehospital cardiopulmonary arrest and
      who received prehospital epinephrine treatment by paramedics, in the periods of
      1994 to 1997 and 2003 to 2004, were included in the study. RESULTS: In the 1994
      to 1997 cohort, we identified 104 subjects in prehospital cardiopulmonary arrest
      who received epinephrine with a documented weight and route of administration.
      Only 29 of 104 subjects in the 1994 to 1997 cohort received the correct dose,
      whereas 46 of 104 subjects received a first dose within 20% of the correct dose.
      In the 2003 to 2004 cohort, we identified 41 children < or = 12 years of age who
      were in cardiopulmonary arrest and received prehospital epinephrine treatment but
      4 children were excluded, leaving 37 subjects. Twenty-one of 37 subjects received
      the correct dose, whereas 24 of 37 subjects received a dose within 20%. The odds
      ratio for obtaining the correct epinephrine dose after the system changes versus
      before was 3.0, and that for obtaining a dose within 20% of the correct dose was
      2.5. CONCLUSIONS: The program seems to have resulted in reduction of the rate of
      epinephrine dosing errors in the prehospital treatment of children in
      cardiopulmonary arrest in Los Angeles County.

PMID- 17015541
TI  - Ultrasound examination of extensive limb swelling reactions after diphtheria
      tetanus-acellular pertussis or reduced-antigen content diphtheria-tetanus
      acellular pertussis immunization in preschool-aged children.
AB  - OBJECTIVE: The aim of this study was to determine the site, extent, and
      resolution of tissue involvement when extensive limb swelling occurred in the
      injected limb for children who received diphtheria-tetanus-acellular pertussis or
      reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine at 4 to 6
      years of age. METHODS: Children who had experienced an injection site reaction at
      18 months of age were assigned randomly to receive an intramuscular injection of
      either reduced-antigen content diphtheria-tetanus-acellular pertussis vaccine or
      diphtheria-tetanus-acellular pertussis vaccine between 4 and 6 years of age.
      Children who developed extensive limb swelling were recruited for assessment by
      clinical examination; ultrasound studies of the affected and opposite (control)
      arms were performed 24 to 48 hours after immunization and 48 to 96 hours later.
      RESULTS: Twelve children with extensive limb swelling were enrolled in the study.
      Ultrasound examinations demonstrated swelling of both the subcutaneous and muscle
      layers of the vaccinated arm. Ultrasound assessment showed that the swelling
      exceeded the clinical measurements of skin redness and swelling. Subcutaneous and
      muscle tissues expanded to 281% and 111% of the tissue thicknesses of the control
      arm, respectively. Repeat ultrasound examinations after 48 to 96 hours showed
      considerable resolution of muscle swelling, compared with subcutaneous tissue
      swelling. There was no significant difference in the extent of swelling detected
      between children who received diphtheria-tetanus-acellular pertussis vaccine and
      those who received reduced-antigen content diphtheria-tetanus-acellular pertussis
      vaccine. CONCLUSION: Extensive limb swelling reactions after diphtheria-tetanus
      acellular pertussis or reduced-antigen content booster immunizations involved
      swelling of subcutaneous and muscle tissues with swelling and duration more
      marked in subcutaneous tissue.

PMID- 17015542
TI  - The burden of diabetes mellitus among US youth: prevalence estimates from the
      SEARCH for Diabetes in Youth Study.
AB  - OBJECTIVE: Our goal was to estimate the prevalence of diabetes mellitus in youth
      <20 years of age in 2001 in the United States, according to age, gender,
      race/ethnicity, and diabetes type. METHODS: The SEARCH for Diabetes in Youth
      Study is a 6-center observational study conducting population-based ascertainment
      of physician-diagnosed diabetes in youth. Census-based denominators for 4
      geographically based centers and enrollment data for 2 health plan-based centers
      were used to calculate prevalence. Age-, gender-, and racial/ethnic group
      specific prevalence rates were multiplied by US population counts to estimate the
      total number of US youth with diabetes. RESULTS: We identified 6379 US youth with
      diabetes in 2001, in a population of approximately 3.5 million. Crude prevalence
      was estimated as 1.82 cases per 1000 youth, being much lower for youth 0 to 9
      years of age (0.79 cases per 1000 youth) than for those 10 to 19 years of age
      (2.80 cases per 1000 youth). Non-Hispanic white youth had the highest prevalence
      (1.06 cases per 1000 youth) in the younger group. Among 10- to 19-year-old youth,
      black youth (3.22 cases per 1000 youth) and non-Hispanic white youth (3.18 cases
      per 1000 youth) had the highest rates, followed by American Indian youth (2.28
      cases per 1000 youth), Hispanic youth (2.18 cases per 1000 youth), and
      Asian/Pacific Islander youth (1.34 cases per 1000 youth). Among younger children,
      type 1 diabetes accounted for > or = 80% of diabetes; among older youth, the
      proportion of type 2 diabetes ranged from 6% (0.19 cases per 1000 youth for non
      Hispanic white youth) to 76% (1.74 cases per 1000 youth for American Indian
      youth). We estimated that 154,369 youth had physician-diagnosed diabetes in 2001
      in the United States. CONCLUSIONS: The overall prevalence estimate for diabetes
      in children and adolescents was approximately 0.18%. Type 2 diabetes was found in
      all racial/ethnic groups but generally was less common than type 1, except in
      American Indian youth.

PMID- 17015543
TI  - Factors associated with establishing a causal diagnosis for children with
      cardiomyopathy.
AB  - OBJECTIVE: The goal was to identify the clinical variables associated with
      establishing a cause of cardiomyopathy in children. METHODS: The Pediatric
      Cardiomyopathy Registry contains clinical and causal testing information for 916
      children who were diagnosed as having cardiomyopathy in North America between
      1990 and 1995. Children with a causal diagnosis were compared with those without
      with respect to several demographic, clinical, and causal testing variables.
      RESULTS: Cardiomyopathy was 1 of 4 types, hypertrophic (34.2%), dilated (53.8%),
      restrictive (3.2%), or other or mixed (8.9%). Only one third of cases had a known
      cause. Children with a known cause for hypertrophic cardiomyopathy were more
      likely to be female, to be relatively smaller, to present with congestive heart
      failure, and to have increased left ventricular posterior wall thickness without
      outflow tract obstruction. For dilated cardiomyopathy, a known cause was
      associated with older age, lower heart rate, smaller left ventricular dimensions,
      and greater shortening fraction. Family history of cardiomyopathy predicted a
      significantly higher rate of causal diagnoses for all cardiomyopathy types,
      whereas family histories of genetic syndromes and sudden death were also
      predictive of a cause for hypertrophic and dilated cardiomyopathies. For
      hypertrophic cardiomyopathy, only blood and urine testing was associated with a
      causal diagnosis, whereas both viral serologic testing or culture and
      endomyocardial biopsy were independent predictors of a causal diagnosis in
      dilated cardiomyopathy. CONCLUSIONS: Certain patient characteristics, family
      history, echocardiographic findings, laboratory testing, and biopsy were
      associated significantly with establishing a cause of pediatric cardiomyopathy.
      Early endomyocardial biopsy should be considered strongly for children with
      dilated cardiomyopathy, for definitive diagnosis of viral myocarditis. Although
      not widely used, skeletal muscle biopsy may yield a cause for some patients with
      hypertrophic cardiomyopathy and for patients suspected of having a mitochondrial
      disorder.

PMID- 17015544
TI  - Comparison of the 4-digit diagnostic code and the Hoyme diagnostic guidelines for
      fetal alcohol spectrum disorders.
AB  - OBJECTIVE: The 4-Digit Diagnostic Code for fetal alcohol spectrum disorders and
      the Hoyme fetal alcohol spectrum disorders diagnostic guidelines differ markedly.
      The performances of the 2 diagnostic systems were compared. METHODS: The fetal
      alcohol syndrome diagnostic criteria from the 4-Digit Code and Hoyme guidelines
      were applied to 952 patients who had received an interdisciplinary, fetal alcohol
      spectrum disorders, diagnostic evaluation at the University of Washington with
      the 4-Digit Diagnostic Code and 16 children with confirmed absence of prenatal
      alcohol exposure. RESULTS: The prevalence of fetal alcohol syndrome was 3.7% with
      the 4-Digit Code and 4.1% with the Hoyme guidelines. Although the prevalences
      were similar, the patients identified were not. Only 17 individuals met the fetal
      alcohol syndrome criteria for both systems. An extraordinary number of patients
      (35%) met the Hoyme criteria for the fetal alcohol syndrome facial phenotype, but
      only 39 of those 330 patients met the Hoyme criteria for fetal alcohol syndrome.
      Even some children with no alcohol exposure (25%) had the Hoyme fetal alcohol
      syndrome face. The specificities of the Hoyme fetal alcohol syndrome face for the
      Hoyme fetal alcohol syndrome diagnosis and prenatal alcohol exposure were low in
      these populations. CONCLUSIONS: Without a specific facial phenotype, a valid
      diagnosis of fetal alcohol syndrome cannot be rendered for patients with prenatal
      alcohol exposure, because a causal link between their outcomes and exposure
      cannot be established, and a valid diagnosis of fetal alcohol syndrome cannot be
      rendered for patients with unknown alcohol exposure, because the face cannot
      serve as a valid proxy measure for alcohol exposure. Diagnostic guidelines must
      confirm the specificity of their fetal alcohol syndrome facial criteria to
      validate their diagnostic criteria.

PMID- 17015545
TI  - Payments to children and adolescents enrolled in research: a pilot study.
AB  - OBJECTIVES: The goal was to identify current payment practices in research
      involving children. METHODS: A 4-page survey was mailed to the first author or
      corresponding author of pediatric research studies. Questions concerned whether
      children enrolled in research and/or their parents received any form of payment,
      values and types of remuneration, federal categories of pediatric research under
      which studies were approved, institutional policies regarding payments to
      children and/or their parents, institutional review board review of payment
      plans, factors that influenced payment decisions, prorating of payments, purposes
      of payments, perceived effects of payments on recruitment, and investigators'
      attitudes toward payments and the perceived risks and discomforts of studies.
      RESULTS: Payment practices varied, and the reasons for which investigators
      adopted particular payment practices varied. Approximately one half offered
      payment. The most popular form of payment was cash. The number of institutions
      with policies addressing directly payments for children enrolled in research has
      increased, but still only approximately one half of institutions studied had such
      policies in place. CONCLUSIONS: Awareness of the variations in payment practices
      and policies and additional study of the ethical issues surrounding payments for
      research participation are essential for building consensus and developing the
      guidelines the Institute of Medicine has said are necessary. Additional research
      also is needed to understand why parents enroll their children in research, how
      payments affect research participation decisions, and what the relationship
      between a study's risks and discomforts and payment should be.

PMID- 17015546
TI  - The effects of adult-type hypolactasia on body height growth and dietary calcium
      intake from childhood into young adulthood: a 21-year follow-up study--the
      Cardiovascular Risk in Young Finns Study.
AB  - OBJECTIVE: The effect of adult-type hypolactasia, caused by the lactase-phlorizin
      hydrolase C/C-13910 genotype, on growth is unknown. We studied whether this
      polymorphism was associated with body height growth, the use of milk products, or
      dietary calcium intake. METHODS: A prospective cohort study was performed among
      3596 randomly selected Finnish children and adolescents (3-18 years of age) in
      1980, with reexamination in 1983, 1986, and 2001 (after a 21-year follow-up
      period). Lactase-phlorizin hydrolase C/T-13910 polymorphism was determined for
      2265 participants in 2002. Nutrient intakes were measured for 1137, 858, and 1031
      subjects in 1980, 1986, and 2001, respectively. RESULTS: The lactase-phlorizin
      hydrolase C/T-13910 polymorphism was not related to mean height growth speed for
      either boys or girls or to final mean body height in adulthood. The consumption
      of milk products, protein, and calcium was lowest for female subjects with the
      lactase-phlorizin hydrolase C/C-13910 genotype over the study years, but there
      were no genotype-related differences in the intake of vitamin D. For boys,
      significant differences were found in the consumption of milk products but not in
      the mean dietary intake of calcium, protein, or vitamin D. CONCLUSIONS: The
      lactase-phlorizin hydrolase C/C-13910 genotype was not associated with mean
      growth speed or final mean body height for either boys or girls. However, it
      contributed significantly to milk product consumption and dietary calcium intake
      from childhood into young adulthood.

PMID- 17015547
TI  - Predictors of spontaneous closure of isolated secundum atrial septal defect in
      children: a longitudinal study.
AB  - OBJECTIVES: The goals were to assess the frequency of spontaneous closure of
      isolated secundum atrial septal defect in children and to identify predictors of
      spontaneous atrial septal defect closure. METHODS: A retrospective cohort study
      was performed in a tertiary care pediatric cardiology center. Consecutive
      patients (n = 200) diagnosed as having isolated atrial septal defects (no
      multiple or fenestrated atrial septal defects, no additional congenital heart
      disease, and no syndromes) were monitored for > 6 months with serial 2
      dimensional echocardiography, according to a standardized protocol. RESULTS: The
      median age at diagnosis was 5 months (minimum: 0 months; maximum: 13.9 years).
      The atrial septal defect diameter at diagnosis was 4 to 5 mm in 40% of cases, 6
      to 7 mm in 28% of cases, 8 to 10 mm in 21% of cases, and > 10 mm in 11% of cases.
      The median age at the final follow-up evaluation was 4.5 years (range: 6.8 months
      to 16.2 years). Thirty-four percent of atrial septal defects showed spontaneous
      closure, and 28% decreased to a diameter of < or = 3 mm. Logistic regression
      analysis revealed atrial septal defect diameter and age at diagnosis as
      independent predictors of spontaneous closure or regression to < or = 3-mm defect
      size. Of atrial septal defects with a diameter of 4 to 5 mm at diagnosis, 56%
      showed spontaneous closure, 30% regressed to a diameter of < or = 3 mm, and none
      required surgical closure. Of atrial septal defects with a diameter of > 10 mm at
      diagnosis, none closed spontaneously, whereas 77% required surgical or device
      closure. Gender and observation time were not associated with spontaneous atrial
      septal defect closure or regression to < or = 3 mm. CONCLUSIONS: In the present
      study population of children with atrial septal defects, 62% showed spontaneous
      closure (34%) or regression to < or = 3 mm (28%). Initial atrial septal defect
      diameter was the main predictor of spontaneous closure.

PMID- 17015548
TI  - The contribution of preterm birth to infant mortality rates in the United States.
AB  - OBJECTIVE: Although two thirds of infant deaths in the United States occur among
      infants born preterm (<37 weeks of gestation), only 17% of infant deaths are
      classified as being attributable to preterm birth with the standard
      classification of leading causes of death. To address this apparent discrepancy,
      we sought to estimate more accurately the contribution of preterm birth to infant
      mortality rates in the United States. METHODS: We identified the top 20 leading
      causes of infant death in 2002 in the US linked birth/infant death file. The role
      of preterm birth for each cause was assessed by determining the proportion of
      infants who were born preterm for each cause of death and by considering the
      biological connection between preterm birth and the specific cause of death.
      RESULTS: Of 27970 records in the linked birth/infant death file for 2002, the 20
      leading causes accounted for 22273 deaths (80% of all infant deaths). Among
      infant deaths attributable to the 20 leading causes, we classified 9596 infant
      deaths (34.3% of all infant deaths) as attributable to preterm birth. Ninety-five
      percent of those deaths occurred among infants who were born at <32 weeks of
      gestation and weighed <1500 g, and two thirds of those deaths occurred during the
      first 24 hours of life. CONCLUSIONS: On the basis of this evaluation, preterm
      birth is the most frequent cause of infant death in the United States, accounting
      for at least one third of infant deaths in 2002. The extreme prematurity of most
      of the infants and their short survival indicate that reducing infant mortality
      rates requires a comprehensive agenda to identify, to test, and to implement
      effective strategies for the prevention of preterm birth.

PMID- 17015549
TI  - Achieved versus intended pulse oximeter saturation in infants born less than 28
      weeks' gestation: the AVIOx study.
AB  - OBJECTIVE: The objective of this study was to document pulse oximeter saturation
      levels achieved in the first 4 weeks of life in infants who were born at < 28
      weeks' gestation, compared with the levels that were targeted by local policy,
      and examine factors that are associated with compliance with the target range.
      METHODS: Infants who were < 28 weeks' gestation and < or = 96 hours of age were
      enrolled in a prospective, multicenter cohort study. Oximetry data were collected
      with masked signal-extraction oximeters for a 72-hour period in each of the first
      4 weeks of life. Data were compared with the pulse oximeter saturation target
      range prescribed by local institutional policy. Factors that were associated with
      intended range compliance were identified with hierarchical modeling. RESULTS:
      Fourteen centers from 3 countries enrolled 84 infants with mean +/- SD birth
      weight of 863 +/- 208 g and gestational age of 26 +/- 1.4 weeks. Oxygen
      saturation policy limits ranged between 83% and 92% for lower limits and 92% and
      98% for upper limits. For infants who received respiratory support, median pulse
      oximeter saturation level achieved was 95%. Center-specific medial levels were
      within the intended range at 12 centers. Centers maintained infants within their
      intended range 16% to 64% of the time but were above range 20% to 73% of the
      time. In hierarchical modeling, wider target ranges, higher target range upper
      limits, presence of a policy of setting oximeter alarms close to the target range
      limits, and lower gestational age were associated with improved target range
      compliance. CONCLUSIONS: Success with maintaining the intended pulse oximeter
      saturation range varied substantially among centers, among patients within
      centers, and for individual patients over time. Most noncompliance was above the
      intended range. Methods for improving compliance and the effect of improved
      compliance on neonatal outcomes require additional research.

PMID- 17015550
TI  - Premedication for nonemergent neonatal intubations: a randomized, controlled
      trial comparing atropine and fentanyl to atropine, fentanyl, and mivacurium.
AB  - OBJECTIVE: The purpose of this work was to investigate whether using a muscle
      relaxant would improve intubation conditions in infants, thereby decreasing the
      incidence and duration of hypoxia and time and number of attempts needed to
      successfully complete the intubation procedure. PATIENTS/METHODS: This was a
      prospective, randomized, controlled, 2-center trial. Infants requiring
      nonemergent intubation were randomly assigned to receive atropine and fentanyl or
      atropine, fentanyl, and mivacurium before intubation. Incidence and duration of
      hypoxia were determined at oxygen saturation thresholds of < or = 85%, < or =
      75%, < or = 60%, and < or = 40%. Videotape was reviewed to determine the time and
      number of intubation attempts and duration of action of mivacurium. RESULTS:
      Analysis of 41 infants showed that incidence of oxygen saturation < or = 60% of
      any duration was significantly less in the mivacurium group (55% vs 24%). The
      incidence of saturation level of any duration < or = 85%, 75%, and 40%;
      cumulative time > or = 30 seconds; and time below the thresholds were not
      significantly different. Total procedure time (472 vs 144 seconds) and total
      laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group.
      Successful intubation was achieved in < or = 2 attempts significantly more often
      in the mivacurium group (35% vs 71%). CONCLUSIONS: Premedication with atropine,
      fentanyl, and mivacurium compared with atropine and fentanyl without a muscle
      relaxant decreases the time and number of attempts needed to successfully
      intubate while significantly reducing the incidence of severe desaturation.
      Premedication including a short-acting muscle relaxant should be considered for
      all nonemergent intubations in the NICU.

PMID- 17015551
TI  - Follow-up of a randomized, placebo-controlled trial of postnatal dexamethasone:
      blood pressure and anthropometric measurements at school age.
AB  - OBJECTIVE: The purpose of this work was to evaluate the effects of a 42-day
      tapering course of dexamethasone on blood pressure and anthropometric
      measurements in school-age children who were born with very low birth weight.
      METHODS: Sixty-eight children, who as neonates participated in a randomized
      placebo-controlled trial of a 42-day tapering course of dexamethasone (n = 38,
      dexamethasone; n = 30, placebo) to facilitate weaning from the ventilator, were
      seen at a median of 9 years of age. Participants underwent measurements of
      systolic blood pressure, diastolic blood pressure, mid-arm circumference, triceps
      skinfold thickness, height, and weight. Mann-Whitney U tests were used to compare
      groups, and Spearman coefficients were used to examine correlations between
      variables. RESULTS: Comparing dexamethasone- and placebo-treated children, we
      found no differences in systolic blood pressure, mid-arm circumference, triceps
      skinfold thickness, height, weight, or body mass index. Twenty-nine percent of
      all subjects had systolic blood pressure and/or diastolic blood pressure > or =
      90th percentile for age and gender. Thirty percent of all subjects had body mass
      index > or = 85th percentile for age and gender. CONCLUSIONS: In a group of
      preterm very low birth-weight infants at high risk for chronic lung disease, we
      found no effects of dexamethasone on blood pressure or anthropometric
      measurements at 8 to 11 years of age. Of concern is that a high proportion in
      this sample had blood pressure > or = 90th percentile and/or body mass index > or
      = 85th percentile.

PMID- 17015552
TI  - Gestational age and birth weight in relation to school performance of 10-year-old
      children: a follow-up study of children born after 32 completed weeks.
AB  - BACKGROUND: Children born extremely premature (<28 weeks) or with a very low
      birth weight (<1500 g) have a poorer school performance than children born at
      term with a normal birth weight. Much less is known about children of higher
      gestational ages and birth weights. We studied gestational age after 32 completed
      weeks and birth weight in relation to the child's school performance at the age
      of 10 years. METHODS: We performed a follow-up study of 5319 children born
      between January 1990 and June 1992. We got the information on birth weight and
      gestational age from birth registration forms; when the children were between 9
      and 11 years of age, we gathered information about their school performance
      (reading, spelling, and arithmetic) from questionnaires completed by the parents
      and the children's primary school teachers. RESULTS: The association between
      birth weight and reading, as well as spelling and arithmetic disabilities, showed
      a graded relationship, with children who weighed <2500 g having the highest
      risks. Even children who weighed between 3000 and 3499 g had an increased risk of
      all 3 learning disabilities compared with children who weighed between 3500 and
      4000 g. This association persisted after adjustment for potential cofounders and
      when the analyses were restricted to children born at term (39-40 weeks of
      gestation), suggesting that the association could not be explained by a low
      gestational age. Compared with children born at term, reading and spelling
      difficulties were more often found among children born at gestational age 33 to
      36 weeks and 37 to 38 weeks, whereas there was no relation between gestational
      age and arithmetic difficulties. CONCLUSIONS: Gestational age and birth weight
      were associated with school performance in the 10-year-old child and the
      association extended into the reference range of both birth weight and
      gestational age.

PMID- 17015553
TI  - Achieving family and provider partnerships for children with special health care
      needs.
AB  - BACKGROUND: During the past 2 decades, family-centered care has evolved as the
      standard of care for children with special health care needs. A major principle
      of family-centered care is a strong partnership between the family and provider,
      working together to address issues and barriers to accessing comprehensive care
      and related services. The federal Maternal and Child Health Bureau defines a
      positive family-provider partnership as a core program outcome. Our objective was
      to assess the extent to which families of children with special health care needs
      feel as though they are treated as partners in decision-making by their doctors.
      METHODS: We analyzed the 2001 National Survey of Children With Special Health
      Care Needs, a nationally representative telephone survey of caretakers for 38,866
      children with special health care needs. Bivariate and multivariate statistical
      methods were used to assess the frequency of meeting the partnership core
      outcome, as well as the demographic and socioeconomic predictors of meeting core
      outcome. We also examined the effect of partnership on indicators of access and
      well-being for children with special health care needs. RESULTS: Among children
      with special health care needs, 85.8% of families reported usually or always
      feeling like a partner in their child's care. However, living in poverty,
      minority racial and ethnic status, absence of health insurance, and depressed
      functional ability placed children with special health care needs and their
      families at elevated risk of being without a sense of partnership. We found that
      sense of partnership was associated with improved outcomes across a number of
      important health care measures, including missed school days, access to specialty
      care, satisfaction with care, and unmet needs for child and family services.
      CONCLUSIONS: Results of the survey demonstrated that whereas most families of
      children with special health care needs feel they are partners in the care of
      their child, further work is needed, particularly for poor, uninsured, and
      minority children, as well as those with functional limitations. The survey
      results also demonstrate the importance of partnership; children whose care met
      the partnership core outcome experienced improved access to care and well-being.

PMID- 17015554
TI  - Recruitment bias in a population-based study of children with cerebral palsy.
AB  - OBJECTIVE: The purpose of this analysis was to assess recruitment bias in a
      population-based study of locomotor ability in children with cerebral palsy.
      METHOD: A population-based case register was used as a sampling frame and was
      considered a highly ascertained record of children with the condition. A twin
      track approach to recruitment for the Locomotor Study was adopted through: (1) a
      specialist orthopedic service and (2) a community pediatric network on behalf of
      the case register. The subjects included children with cerebral palsy aged 4 to
      16 years in 2003, able to walk > or = 10 m, and a resident in Northern Ireland,
      as well as their parents. RESULTS: The Orthopaedic Service identified clinically
      distinct children with cerebral palsy in terms of type, severity, age, and
      geographic residence. More families responded to an invitation, and more were
      ultimately recruited into the study via the Orthopaedic Service compared with a
      case register using community pediatric contacts. Overall, 37.8% of the eligible
      cerebral palsy population participated in the Locomotor Study, but there was no
      evidence of any systematic biases in demographic or key clinical characteristics
      when compared with nonparticipants. One follow-up reminder led to an increase in
      recruitment of 10%. CONCLUSIONS: Care must be taken in the recruitment of
      children with cerebral palsy through clinic-based populations, although these
      routes may prove more successful in follow-up. Provided they are comprehensive,
      case registers have a valuable contribution to make to clinical research by
      providing a sampling frame including information on baseline characteristics of
      an affected population.

PMID- 17015555
TI  - Comparison of a personalized parent voice smoke alarm with a conventional
      residential tone smoke alarm for awakening children.
AB  - BACKGROUND: Conventional residential tone smoke alarms fail to awaken the
      majority of children during slow wave sleep. With the objective of identifying a
      more effective smoke alarm for children, we compared a personalized parent voice
      smoke alarm with a conventional residential tone smoke alarm, both presented at
      100 dB, with respect to their ability to awaken children 6- to 12-years-old from
      stage 4 sleep and prompt their performance of a simulated self-rescue escape
      procedure. METHODS: Using a randomized, nonblinded, clinical research design, a
      volunteer sample of healthy children 6- to 12-years-old was enrolled in the
      study. Children were trained how to perform a simulated self-rescue escape
      procedure when they heard a smoke alarm. Each child's mother recorded a voice
      alarm message, "First name! First name! Wake up! Get out of bed! Leave the room!"
      For each child, either the voice or tone smoke alarm was randomly selected and
      triggered during the first cycle of stage 4 sleep, and then the other alarm was
      triggered during the second cycle of stage 4 sleep. Children's sleep stage was
      monitored by electroencephalography, electro-oculography, and chin
      electromyography. The 4 main outcome measures included the number of children who
      awakened, the number of children who escaped, the time to awakening, and the time
      to escape. RESULTS: Twenty-four children were enrolled. The median age was 9
      years, and 11 (46%) were boys. One half of the children received the parent voice
      alarm first, and one half received the tone alarm first; however, the order that
      the alarm stimuli were presented was not statistically associated with awakening
      or escaping. Twenty-three (96%) of the 24 subjects awakened to the parent voice
      alarm compared with 14 (58%) to the tone alarm. One child did not awaken to
      either stimulus. Nine children awakened to their parent's voice but not to the
      tone, whereas none awakened to only the tone and not the voice. Twenty (83%) of
      the subjects in the parent voice alarm group successfully performed the escape
      procedure within 5 minutes of alarm onset compared with 9 (38%) in the tone alarm
      group. The median time to awaken was 20 seconds in the voice alarm group compared
      with 3 minutes in the tone alarm group. The median time to escape was 38 seconds
      in the voice alarm group compared with the maximum allowed 5 minutes in the tone
      alarm group. When exposed to the tone alarm, older children were more likely to
      awaken and were more likely to escape than younger children. There was no
      association between child's age and awakening or escaping for children exposed to
      the parent voice alarm. There was no association between child's gender and
      awakening or escaping for either alarm type. CONCLUSIONS: To our knowledge, this
      study is the first to compare the ability of different types of smoke alarms to
      awaken children while monitoring sleep stage. The personalized parent voice smoke
      alarm at 100 dB successfully awakened 96% of children 6- to 12-years-old from
      stage 4 sleep with 83% successfully performing a simulated self-rescue escape
      procedure, significantly outperforming the 100-dB conventional residential tone
      smoke alarm. These findings suggest a clear direction for future research, as
      well as important fundamental changes in smoke alarm design, that address the
      unique developmental needs of children. The development of a more effective smoke
      alarm for use in homes and other locations where children sleep provides an
      opportunity to reduce fire-related morbidity and mortality among children.

PMID- 17015556
TI  - Comorbidity, hospitalization, and medication use and their influence on mental
      and motor development of young infants with Down syndrome.
AB  - OBJECTIVE: Young infants with Down syndrome have an increased occurrence of
      several well-known medical conditions such as congenital heart and
      gastrointestinal disease. The aim of this study was to establish consequences
      like hospitalization and medication use rates and to determine their possible
      influence on early neurodevelopment. PATIENTS AND METHODS: This study compared 2
      years of thyroxine treatment with placebo in 196 neonates with Down syndrome who
      were included in a previously reported randomized clinical trial. Parents were
      interviewed about comorbidity, hospitalization, and medication use at random
      assignment and regularly thereafter. Data were cross-checked with discharge
      letters when available. The influence of comorbidity on neurodevelopment at 2
      years old (Bayley Scales of Infant Development II) was determined by stepwise
      multiple linear-regression analysis. RESULTS: Before trial entry, 163 infants
      with Down syndrome had been admitted to hospital for an average of 14.01 days,
      whereas during the trial, 95 of 181 infants who completed the trial were
      hospitalized for an average 19.75 days. Main hospitalization reasons during the
      trial were lung/airway and congenital heart and gastrointestinal disease. The 48
      infants operated on for heart or gastrointestinal disease accounted for 1401 of
      the total number of 1876 hospital admission days during the trial and for 33 of
      62 admissions for lung/airway infection. During their second year of life,
      approximately 60% of the infants were prescribed drugs, mostly antibiotics and
      pulmonary. Regression analysis showed infantile spasms, "other" central nervous
      system disease, and gastrointestinal disease necessitating surgery to be
      associated with greater developmental age delays at 24 months old (mental: 6.87,
      3.52, and 1.69 months; and motor: 3.59, 2.54, and 1.68 months, respectively).
      CONCLUSIONS: Hospital admission and medication use rates in young infants with
      Down syndrome are still very high, mainly because of congenital heart and
      gastrointestinal disease and acquired respiratory disease. Central nervous system
      disease and gastrointestinal disease necessitating surgery were independently
      associated with a worse developmental outcome.

PMID- 17015557
TI  - Cerebral outcomes in a preterm baboon model of early versus delayed nasal
      continuous positive airway pressure.
AB  - BACKGROUND: The survival of prematurely born infants has greatly increased in
      recent decades because of advances in neonatal intensive care, which have
      included the advent of ventilatory therapies. However, there is limited knowledge
      as to the impact of these therapies on the developing brain. The purpose of this
      work was to evaluate the influence of randomized respiratory therapy with either
      early continuous positive airway pressure or delayed continuous positive airway
      pressure preceded by positive pressure ventilation on the extent of brain injury
      and altered development in a prematurely delivered primate model. METHODS: Fetal
      baboons were delivered at 125 days of gestation (term: approximately 185 days of
      gestation) by cesarean section. Animals were maintained for 28 days postdelivery
      with either: early continuous positive airway pressure (commencing at 24 hours; n
      = 6) or delayed continuous positive airway pressure (positive pressure
      ventilation for 5 days followed by nCPAP; n = 5). Gestational controls (n = 4)
      were delivered at 153 days of gestation. At the completion of the study, animals
      were killed, the brains were assessed histologically for growth and development,
      and evidence of cerebral injury and indices for both parameters were formulated.
      RESULTS: Brain and body weights were reduced in all of the nasal continuous
      positive airway pressure animals compared with controls; however, the brain/body
      weight ratio was increased in early continuous positive airway pressure animals.
      Within both nasal continuous positive airway pressure groups compared with
      controls, there was increased gliosis in the subcortical and deep white matter
      and cortex and a persistence of radial glia. Early continuous positive airway
      pressure was associated with less cerebral injury than delayed continuous
      positive airway pressure therapy. Neuropathologies were not observed in controls.
      CONCLUSIONS: Premature delivery, in the absence of potentiating factors, such as
      hypoxia or infection, is associated with a decrease in brain growth and the
      presence of subtle brain injury, which seems to be modified by respiratory
      therapies with early continuous positive airway pressure being associated with
      less overall cerebral injury.

PMID- 17015558
TI  - Cumulative index of exposure to hypocarbia and hyperoxia as risk factors for
      periventricular leukomalacia in low birth weight infants.
AB  - BACKGROUND: Hypocarbia and hyperoxia are risk factors for periventricular
      leukomalacia in low birth weight infants. The association of a cumulative index
      of exposure to hypocarbia and hyperoxia and periventricular leukomalacia has not
      been evaluated. OBJECTIVE: Our goal was to examine the relationship between
      cumulative index of exposure to hypocarbia and hyperoxia and periventricular
      leukomalacia during the first 7 days of life in low birth weight infants.
      METHODS: Blood gas results were recorded in 6-hour intervals among low birth
      weight infants in a prospective data registry. Cumulative index of exposure to
      hypocarbia was calculated as the difference between arterial carbon dioxide level
      and 35 mmHg multiplied by the time interval in hours for each 6-hour block in a
      24-hour day for the first 7 days of life. Cumulative index of exposure to
      hyperoxia was calculated in the same manner for arterial oxygen level >80 mm Hg.
      The relationship between exposure to hypocarbia, hyperoxia, and periventricular
      leukomalacia was examined in 778 infants with blood gas and cranial sonography
      data. RESULTS: Twenty-one infants had periventricular leukomalacia. Hypocarbia
      occurred in 489 infants and hyperoxia in 502 infants. Infants with
      periventricular leukomalacia were more likely to have a lower gestational age and
      to require delivery room resuscitation than those without periventricular
      leukomalacia. More infants in the highest quartile of exposure to hypocarbia had
      periventricular leukomalacia compared to those with no hypocarbia. Risk of
      periventricular leukomalacia was increased in infants with the highest quartile
      of exposure to hypocarbia after adjusting for maternal and neonatal variables,
      none to be associated with periventricular leukomalacia. Cumulative index
      exposure to hyperoxia was not related to periventricular leukomalacia.
      CONCLUSIONS: Cumulative exposure to hypocarbia and not hyperoxia was
      independently related to risk of periventricular leukomalacia in low birth weight
      infants.

PMID- 17015559
TI  - The spectrum of valproic acid-associated pancreatitis.
AB  - OBJECTIVE: Our goal was to characterize valproic acid-associated pancreatitis in
      children. PATIENTS AND METHODS: The charts of all patients with pancreatitis
      (diagnosed by using strict criteria) associated with valproic acid during a 10
      year period were reviewed. Clinical and laboratory results were abstracted.
      RESULTS: Twenty-two patients with valproic acid-associated pancreatitis were seen
      during the study period. Symptoms were similar to those of patients with
      pancreatitis from other etiologies and included abdominal pain/tenderness (83%),
      vomiting/retching (74%), abdominal distention (30%), and fever/chills (26%).
      Valproic acid levels were in the therapeutic range in all but 1 patient. The mean
      duration of therapy before the onset of pancreatitis was 32 months. The serum
      lipase level was >3 times the reference value in all patients, but the serum
      amylase level was not significantly elevated in 31% of the patients tested.
      Imaging studies altered clinical management in only 1 patient. The length of stay
      was generally brief (mean: 8 days). Two patients died. Of the 5 patients who were
      rechallenged, 4 had relapses. CONCLUSIONS: Valproic acid-associated pancreatitis
      does not depend on valproic acid serum level and may occur any time after the
      onset of therapy. The serum lipase level is more sensitive than the serum amylase
      level and should be obtained when pancreatitis is suspected. Early imaging
      studies did not change clinical management. Rechallenge with valproic acid is
      dangerous and should be avoided.

PMID- 17015560
TI  - No evidence of persisting measles virus in peripheral blood mononuclear cells
      from children with autism spectrum disorder.
AB  - OBJECTIVES: Despite epidemiologic evidence to the contrary, claims of an
      association between measles-mumps-rubella vaccination and the development of
      autism have persisted. Such claims are based primarily on the identification of
      measles virus nucleic acids in tissues and body fluids by polymerase chain
      reaction. We sought to determine whether measles virus nucleic acids persist in
      children with autism spectrum disorder compared with control children. PATIENTS
      AND METHODS: Peripheral blood mononuclear cells were isolated from 54 children
      with autism spectrum disorder and 34 developmentally normal children, and up to 4
      real-time polymerase chain reaction assays and 2 nested polymerase chain reaction
      assays were performed. These assays targeted the nucleoprotein, fusion, and
      hemagglutinin genes of measles virus using previously published primer pairs with
      detection by SYBR green I. Our own real-time assay targeted the fusion gene using
      novel primers and an internal fluorescent probe. Positive reactions were
      evaluated rigorously, and amplicons were sequenced. Finally, anti-measles
      antibody titers were measured by enzyme immunoassay. RESULTS: The real-time
      assays based on previously published primers gave rise to a large number of
      positive reactions in both autism spectrum disorder and control samples. Almost
      all of the positive reactions in these assays were eliminated by evaluation of
      melting curves and amplicon band size. The amplicons for the remaining positive
      reactions were cloned and sequenced. No sample from either autism spectrum
      disorder or control groups was found to contain nucleic acids from any measles
      virus gene. In the nested polymerase chain reaction and in-house assays, none of
      the samples yielded positive results. Furthermore, there was no difference in
      anti-measles antibody titers between the autism and control groups.
      INTERPRETATION: There is no evidence of measles virus persistence in the
      peripheral blood mononuclear cells of children with autism spectrum disorder.

PMID- 17015561
TI  - The impact of public insurance expansions on children's access and use of care.
AB  - OBJECTIVE: Our goal was to examine the impact of the State Children's Health
      Insurance Program nationally on children's access and use of health care.
      OBJECTIVE: Our data source was the National Health Interview Survey, using 1997
      as a baseline, which predates the implementation of the State Children's Health
      Insurance Program, and 2003 as the end point of the analysis. We analyzed 25,734
      children aged 0 to 18 years (1997 and 2003 combined) to examine changes in health
      insurance coverage rates, health care access, and utilization for children in the
      State Children's Health Insurance Program target population, defined here as
      those living in families with incomes between 100% and 199% of the federal
      poverty level. RESULTS: Children in the State Children's Health Insurance Program
      target income group showed the largest reduction in rates of uninsurance among 3
      income groups (< 100%, 100%-199%, and > or = 200% of the federal poverty level)
      between 1997 and 2003 (15.1%-8.7%). Significant reductions occurred in the
      proportion of children without a usual source of care in the target income group
      (9.4%-7.3%) and in the proportion of children without a provider visit in the
      past year (10.8%-9.8%). Other measures (unmet needs, delayed care, volume of
      provider visits, receipt of well-child care, and dental care) showed no
      significant changes over this time period. A separate multivariate analysis
      restricted to the State Children's Health Insurance Program target population in
      2003 showed that children with continuous public coverage had significantly
      better access and utilization on all measures studied when compared with
      uninsured children and performed as well or better than children with continuous
      private coverage. CONCLUSIONS: Implementation of the State Children's Health
      Insurance Program is associated with substantial gains in public coverage for
      children in the target income group. Although some of these gains were offset by
      losses in private coverage, our findings demonstrate that public health insurance
      provides significant benefits in terms of access and utilization for children
      living in the target income group.

PMID- 17015562
TI  - Pediatric precursors of adult cardiovascular disease: noninvasive assessment of
      early vascular changes in children and adolescents.
AB  - BACKGROUND: Until recently, our understanding of the childhood antecedents of
      adult cardiovascular disease was limited mainly to autopsy studies and pathologic
      findings in teens and young adults who died from accidental causes. Recent
      advances in the understanding of atherosclerosis and new technologies allowing
      detection of early events have made it possible to observe anatomic and
      physiologic evidence of cardiovascular disease in young adults and children.
      OBJECTIVES: The goal of this article was to introduce pediatricians to new
      methods for noninvasive measurement of cardiovascular disease and its precursors,
      to describe the potential application of these techniques in detecting childhood
      precursors of adult cardiovascular disease, and to summarize knowledge gained
      from this approach. METHODS: We conducted a computerized search of peer-reviewed
      articles listed in PubMed and Medline from 1980 to April 2006. We reviewed 63 and
      84 articles from the adult and pediatric literature, respectively. RESULTS:
      Reviewing the research on childhood antecedents of adult cardiovascular disease
      is sobering. Vascular alterations in anatomy, physiology, mechanical properties,
      and proinflammatory and prothrombotic changes are present from a very early age
      of childhood and are associated with the risk factors common in adult
      cardiovascular disease. At the same time, this body of research supports the
      concept that the vascular impairment from childhood may improve over time with
      appropriate intervention. CONCLUSIONS: The measurement tools and concepts
      described in this article offer diagnostic and therapeutic opportunities for
      collaboration between clinical pediatricians and pediatric researchers. These
      partnerships will enable pediatricians to contribute in an effort to reduce the
      burdens of cardiovascular disease to individuals, families, and society.

PMID- 17015563
TI  - Rethinking well-child care in the United States: an international comparison.
AB  - BACKGROUND: The increasing scope of health supervision recommendations challenges
      well-child care delivery in the United States. Comparison of the United States
      with other countries' delivery systems may highlight different assumptions as
      well as structural approaches for consideration. OBJECTIVE: Our goal was to
      describe the process of well-child care delivery in industrialized nations and
      compare it to the US model of child health care. METHODS: Literature reviews and
      international experts were used to identify 10 countries with unique features of
      well-child care delivery for comparison to the United States. Key-informant
      interviews using a structured protocol were held with child health experts in 10
      countries to delineate the structural and practice features of their systems.
      Site visits produced additional key informant data from 5 countries (The
      Netherlands, England, Australia, Sweden, and France). RESULTS: A primary care
      framework was adapted to analyze structural and practice features of well-child
      care in the 10 countries. Although well-child care content is similar, there are
      marked differences in the definitions of well-child care and the scope of
      practice of primary care professionals and pediatricians specifically who provide
      this care across the 10 countries. In contrast to the United States, none of the
      countries place all well-child care components under the responsibility of a
      single primary care provider. Well-child care services and care for acute,
      chronic, and behavioral/developmental problems are often provided by different
      clinicians and within different service systems. CONCLUSIONS: Despite some
      similarities, well-child care models from other countries differ from the United
      States in key structural features on the basis of broad financing differences as
      well as specific visions for effective well-child care services. Features of
      these models can inform child health policy makers and providers in rethinking
      how desired improvements in US well-child care delivery might be sought.

PMID- 17015564
TI  - Otitis media: the need for a new paradigm in medical education.

PMID- 17015565
TI  - Pediatric health maintenance in the 21st century: a view from the trenches.

PMID- 17015566
TI  - Too hot, too cold: issues with vaccine storage.

PMID- 17015567
TI  - Oxygen therapy in preterm infants: hitting the target.

PMID- 17015568
TI  - Race, ethnicity, and breastfeeding.

PMID- 17015569
TI  - Has the measles-mumps-rubella vaccine been fully exonerated?

PMID- 17015570
TI  - Adverse effects in children after unintentional buprenorphine exposure.
AB  - Buprenorphine in sublingual formulation was recently introduced to the American
      market for treatment of opioid dependence. We report a series of 5 toddlers with
      respiratory and mental-status depression after unintentional buprenorphine
      exposure. Despite buprenorphine's partial agonist activity and ceiling effect on
      respiratory depression, all children required hospital admission and either
      opioid-antagonist therapy or mechanical ventilation. Results of routine urine
      toxicology screening for opioids were negative in all cases. Confirmatory testing
      was sent for 1 child and returned with a positive result. The increasing use of
      buprenorphine as a home-based therapy for opioid addiction in the United States
      raises public health concerns for the pediatric population.

PMID- 17015571
TI  - Prevention of sexual harassment in the workplace and educational settings.
AB  - The American Academy of Pediatrics is committed to working to ensure that
      workplaces and educational settings in which pediatricians spend time are free of
      sexual harassment. The purpose of this statement is to heighten awareness and
      sensitivity to this important issue, recognizing that institutions, clinics, and
      office-based practices may have existing policies.

PMID- 17015572
TI  - Child life services.
AB  - Child life programs have become standard in most large pediatric centers and even
      on some smaller pediatric inpatient units to address the psychosocial concerns
      that accompany hospitalization and other health care experiences. The child life
      specialist focuses on the strengths and sense of well-being of children while
      promoting their optimal development and minimizing the adverse effects of
      children's experiences in health care or other potentially stressful settings.
      Using play and psychological preparation as primary tools, child life
      interventions facilitate coping and adjustment at times and under circumstances
      that might prove overwhelming otherwise. Play and age-appropriate communication
      may be used to (1) promote optimal development, (2) present information, (3) plan
      and rehearse useful coping strategies for medical events or procedures, (4) work
      through feelings about past or impending experiences, and (5) establish
      therapeutic relationships with children and parents to support family involvement
      in each child's care, with continuity across the care continuum. The benefits of
      this collaborative work with the family and health care team are not limited to
      the health care setting; it may also optimize reintegration into schools and the
      community.

PMID- 17015573
TI  - Pediatric mental health emergencies in the emergency medical services system.
AB  - Emergency departments are vital in the management of pediatric patients with
      mental health emergencies. Pediatric mental health emergencies are an increasing
      part of emergency medical practice because emergency departments have become the
      safety net for a fragmented mental health infrastructure that is experiencing
      critical shortages in services in all sectors. Emergency departments must safely,
      humanely, and in a culturally and developmentally appropriate manner manage
      pediatric patients with undiagnosed and known mental illnesses, including those
      with mental retardation, autistic spectrum disorders, and attention
      deficit/hyperactivity disorder and those experiencing a behavioral crisis.
      Emergency departments also manage patients with suicidal ideation, depression,
      escalating aggression, substance abuse, posttraumatic stress disorder, and
      maltreatment and those exposed to violence and unexpected deaths. Emergency
      departments must address not only the physical but also the mental health needs
      of patients during and after mass-casualty incidents and disasters. The American
      Academy of Pediatrics and the American College of Emergency Physicians support
      advocacy for increased mental health resources, including improved pediatric
      mental health tools for the emergency department, increased mental health
      insurance coverage, and adequate reimbursement at all levels; acknowledgment of
      the importance of the child's medical home; and promotion of education and
      research for mental health emergencies.

PMID- 17015574
TI  - Payment for telephone care.
AB  - Telephone care in pediatrics requires medical judgment, is associated with
      practice expense and medical liability risk, and can often substitute for more
      costly face-to-face care. Despite this, physicians are infrequently paid by
      patients or third-party payors for medical services provided by telephone. As the
      costs of maintaining a practice continue to increase, pediatricians are
      increasingly seeking payment for the time and work involved in telephone care.
      This statement reviews the role of telephone care in pediatric practice, the
      current state of payment for telephone care, and the practical issues associated
      with charging for telephone care services, a service traditionally provided
      gratis to patients and families. Specific recommendations are presented for
      appropriate documenting, reporting, and billing for telephone care services.

PMID- 17015575
TI  - Diagnosis and management of bronchiolitis.
AB  - Bronchiolitis is a disorder most commonly caused in infants by viral lower
      respiratory tract infection. It is the most common lower respiratory infection in
      this age group. It is characterized by acute inflammation, edema, and necrosis of
      epithelial cells lining small airways, increased mucus production, and
      bronchospasm. The American Academy of Pediatrics convened a committee composed of
      primary care physicians and specialists in the fields of pulmonology, infectious
      disease, emergency medicine, epidemiology, and medical informatics. The committee
      partnered with the Agency for Healthcare Research and Quality and the RTI
      International-University of North Carolina Evidence-Based Practice Center to
      develop a comprehensive review of the evidence-based literature related to the
      diagnosis, management, and prevention of bronchiolitis. The resulting evidence
      report and other sources of data were used to formulate clinical practice
      guideline recommendations. This guideline addresses the diagnosis of
      bronchiolitis as well as various therapeutic interventions including
      bronchodilators, corticosteroids, antiviral and antibacterial agents, hydration,
      chest physiotherapy, and oxygen. Recommendations are made for prevention of
      respiratory syncytial virus infection with palivizumab and the control of
      nosocomial spread of infection. Decisions were made on the basis of a systematic
      grading of the quality of evidence and strength of recommendation. The clinical
      practice guideline underwent comprehensive peer review before it was approved by
      the American Academy of Pediatrics. This clinical practice guideline is not
      intended as a sole source of guidance in the management of children with
      bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It
      is not intended to replace clinical judgment or establish a protocol for the care
      of all children with this condition. These recommendations may not provide the
      only appropriate approach to the management of children with bronchiolitis.

PMID- 17015576
TI  - H2-blocker therapy and necrotizing enterocolitis for very low birth weight
      preterm infants.

PMID- 17015577
TI  - Effect of predischarge bilirubin screening on subsequent hyperbilirubinemia.

PMID- 17015578
TI  - Predictors of fatality in hemolytic uremic syndrome lack numbers.

PMID- 17015579
TI  - Predictors of fatality in hemolytic uremic syndrome lack numbers.

PMID- 17015580
TI  - Potential polygenic influences on chronic fatigue syndrome.

PMID- 17015581
TI  - Assent in pediatric research.

PMID- 17015582
TI  - The physical, emotional, and financial trauma incurred by infants and their
      families when an existing condition is not detected by newborn screening.

PMID- 17015583
TI  - Does breastfeeding prevent nocturnal enuresis?

PMID- 17015584
TI  - Breastfeeding during infancy and bed-wetting during childhood.

PMID- 17015585
TI  - Parental restrictions on adolescent internet use.

PMID- 17015586
TI  - The influence of cognitive function on outcome after a hip fracture.
AB  - BACKGROUND: Previous studies have indicated that patients with a hip fracture who
      have impaired cognitive function have an increased risk for complications, poor
      long-term outcome, and an increased mortality rate. An assessment of cognitive
      function is often lacking in nursing and medical records. We investigated whether
      an assessment of cognitive function obtained with use of a validated instrument
      would be a useful patient management adjunct. METHODS: We studied 213 patients
      with a hip fracture who had a mean age of eighty-four years and were entered in a
      prospective trial with a follow-up evaluation at four and twelve months. On
      admission to the orthopaedic ward, the patients were evaluated with use of the
      Short Portable Mental Status Questionnaire to assess their cognitive function.
      The outcome for patients with severe cognitive dysfunction, i.e., those with a
      score of <3 on the questionnaire, was compared with the outcome for patients with
      higher scores. The main outcome measurements were the Charnley hip score,
      activities of daily living status, health-related quality of life, and mortality.
      RESULTS: A Short Portable Mental Status Questionnaire score of <3 and male gender
      were associated with an increased mortality rate during the first twelve months.
      Moreover, patients with a score of <3 had a significantly worse outcome with
      regard to the ability to walk and to perform the activities of daily living, with
      36% of these patients confined to a wheelchair and almost 39% totally dependent
      with regard to daily living functions at the time of the final follow-up (p <
      0.001). CONCLUSIONS: The systematic use of the Short Portable Mental Status
      Questionnaire upon admission to the orthopaedic ward identifies patients with a
      hip fracture who have severe cognitive dysfunction and effectively predicts their
      outcome with regard to the ability to walk, ability to perform the activities of
      daily living, and mortality, and it can be recommended for use in the care of
      elderly patients with a hip fracture.

PMID- 17015587
TI  - Are patients being transferred to level-I trauma centers for reasons other than
      medical necessity?
AB  - BACKGROUND: In the United States, the Emergency Medical Treatment and Active
      Labor Act defines broad guidelines regarding interhospital transfer of patients
      who have sought care in the emergency department. However, patient transfers for
      nonmedical reasons are still considered a common practice. The purpose of this
      study was to evaluate the possible risk factors for hospital transfer in a
      population of patients unlikely to require transfer to a level-I center for
      medical reasons. METHODS: A retrospective case-control national database study
      was performed with use of data from the National Trauma Data Bank (version 4.3).
      The study group consisted of patients with low Injury Severity Scores (< or =9)
      who were transferred to a level-I trauma center from another hospital. The
      controls were patients with low Injury Severity Scores who were treated at any
      hospital that was lower than a level-I trauma center and were not transferred.
      Hypothesized risk factors for hospital transfer were the age, gender, race, and
      insurance status of the patient; the time of day the transfer was received; and
      the number and type of comorbidities. RESULTS: The total sample included 97,393
      patients, 21% of whom were transferred to a level-I trauma center. The odds
      ratios adjusted for all risk factors indicated that transfer rates were higher
      for male patients compared with female patients (adjusted odds ratio = 1.46),
      children compared with seniors (3.54), blacks compared with whites (1.28),
      evening or night transfers compared with morning or afternoon transfers (2.25),
      patients with Medicaid compared with those with other types of insurance (2.02),
      and for those with one or more comorbidities compared with those with no
      comorbidity (2.79). CONCLUSIONS: These results suggest the need for prospective
      studies to further investigate the relationships between hospital transfer and
      medical and nonmedical factors.

PMID- 17015588
TI  - Prevalence, concordance, and heritability of Scheuermann kyphosis based on a
      study of twins.
AB  - BACKGROUND: The purpose of this study was to establish a cohort of symptomatic
      twins with Scheuermann kyphosis to provide estimates of prevalence, concordance,
      odds ratio, and heritability. These estimates indicate to what extent genetic
      factors contribute to the etiology of this disease. METHODS: The Odense-based
      Danish Twin Registry is unique in that it contains data on all 73,000 twin pairs
      born in Denmark over the last 130 years. For the present study, all 46,418 twins
      born from 1931 through 1982 received a seventeen-page questionnaire, in which one
      question was "Have you been diagnosed with Scheuermann disease by a doctor"? The
      prevalence of self-reported Scheuermann disease was calculated, with the total
      number of answers used as the general population. Pairwise and probandwise
      concordance, odds ratio, tetrachoric correlations, and heritability were
      calculated. RESULTS: We found that the overall prevalence of Scheuermann disease
      was 2.8%, with a prevalence of 2.1% among women and 3.6% among men (p < 0.0001).
      The pairwise concordance for monozygotic twins was 0.19 compared with 0.07 for
      dizygotic twins. The probandwise concordance was 0.31 for monozygotic twins and
      0.13 for dizygotic twins. The odds ratios were 32.92 and 6.25 in the monozygotic
      and dizygotic twins, respectively. These differences were significant (p < 0.01).
      Heritability was 74%. CONCLUSIONS: In a large cohort of twins that included
      almost 35,000 individuals, the self-reported overall prevalence of Scheuermann
      disease was 2.8% and the male-to-female ratio was close to 2:1. Because the
      pairwise and probandwise concordance and the odds ratio were two to three times
      higher in monozygotic than in dizygotic twins and the heritability was high, we
      concluded that there is a major genetic contribution to the etiology of
      Scheuermann disease.

PMID- 17015589
TI  - Reconstruction of segmental bone defects due to chronic osteomyelitis with use of
      an external fixator and an intramedullary nail.
AB  - BACKGROUND: Callus distraction over an intramedullary nail is a rarely used
      technique for the reconstruction of intercalary defects of the femur and tibia
      after radical debridement of chronic osteomyelitic foci. The aim of this study
      was to summarize our experience with distraction osteogenesis performed with an
      external fixator combined with an intramedullary nail for the treatment of bone
      defects and limb-shortening resulting from radical debridement of chronic
      osteomyelitis. METHODS: Thirteen patients who ranged in age from eighteen to
      sixty-three years underwent radical debridement to treat a nonunion associated
      with chronic osteomyelitis of the tibia (seven patients) and femur (six
      patients). The lesions were classified, according to the Cierny-Mader
      classification system, as type IVA (nine) and type IVB (four). The resulting
      segmental defects and any limb-length discrepancy were then reconstructed with
      use of distraction osteogenesis over an intramedullary nail. Two patients
      required a local gastrocnemius flap. Free nonvascularized fibular grafts were
      added to the distraction site for augmentation of a femoral defect at the time of
      external fixator removal and locking of the nail in two patients. At the time of
      the latest follow-up, functional and radiographic results were evaluated with use
      of the criteria of Paley et al. RESULTS: The mean size of the defect was 10 cm
      (range, 6 to 13 cm) in the femur and 7 cm (range, 5 to 10 cm) in the tibia. The
      mean external fixator index was 13.5 days per centimeter, the consolidation index
      was 31.7 days/cm, and the mean time to union at the docking site was nine months
      (range, five to sixteen months). At a mean follow-up of 47.3 months, eleven of
      the thirteen patients had an excellent result in terms of both bone and
      functional assessment. There were two recurrences of infection necessitating nail
      removal. These patients underwent revision with an Ilizarov fixator.
      Subsequently, the infection was controlled and the nonunions healed. CONCLUSIONS:
      This combined method may prove to be an improvement on the classic techniques for
      the treatment of a nonunion of a long bone associated with chronic osteomyelitis,
      in terms of external fixation period and consolidation index. The earlier removal
      of the external fixator is associated with increased patient comfort, a decreased
      complication rate, and a convenient and rapid rehabilitation.

PMID- 17015590
TI  - Bilateral total knee replacement: staging and pulmonary embolism.
AB  - BACKGROUND: When a bilateral total knee replacement is indicated, it is not clear
      whether it is preferable to operate on both knees during the same hospitalization
      (simultaneously) or to stage the procedures in two separate hospital stays. A
      greater risk of pulmonary embolism after simultaneous total knee replacement has
      been reported by some authors, but little national data are available. METHODS:
      We reviewed the records of 122,385 United States Medicare enrollees who had had a
      total knee replacement in 2000. We noted whether they had had a unilateral
      procedure or two procedures and, if they had had two procedures, whether both had
      been done during the same hospitalization or whether the operations had been
      performed during two separate hospital stays. Age, sex, race, residence, Medicaid
      eligibility (a proxy for low income), and the Charlson comorbidity score were
      documented for each patient as were the total numbers of total knee replacements
      performed in the year 2000 by the hospital and the surgeon. The probability of a
      symptomatic pulmonary embolism developing in the first three months after surgery
      was calculated for the simultaneous, staged, and unilateral procedures. RESULTS:
      Simultaneous procedures were much more likely to be performed in high-volume
      hospitals and by high-volume surgeons than were staged procedures. Men had
      proportionately more simultaneous procedures than did women. Hospitals in the
      northeastern United States were the most likely to perform simultaneous
      procedures. A pulmonary embolism developed in the first three months in 0.81% of
      the patients who had had a single procedure compared with 1.44% of the patients
      who had undergone a simultaneous procedure (adjusted hazard ratio 1.81; 95%
      confidence interval, 1.49, 2.20). CONCLUSIONS: The systematic differences in
      patient gender, hospital and surgeon volume, and geographic region between those
      who undergo simultaneous total knee replacements and those who undergo staged
      procedures should be borne in mind when outcomes are being compared. The adjusted
      risk of pulmonary embolism is about 80% higher in the three months after a
      simultaneous procedure than in the three months after a single procedure, which
      suggests that the sum of the risks associated with the two operations of a staged
      procedure may equal or exceed the risk of simultaneous total knee replacement.

PMID- 17015591
TI  - Influence of acetabular coverage on hip survival after free vascularized fibular
      grafting for femoral head osteonecrosis.
AB  - BACKGROUND: Osteonecrosis of the femoral head frequently results in collapse of
      the head and subsequent arthrosis of the joint. Surgical treatment has been based
      entirely on the evaluation of the femoral side of the hip joint, with little
      consideration given to the possible influence on outcome of the orientation of
      the acetabulum. METHODS: We retrospectively reviewed a consecutive series of 200
      hips in 160 patients with osteonecrosis of the femoral head who had undergone
      free vascularized fibular grafting between 1997 and 1998. The mean duration of
      clinical follow-up was 7.5 years. Ninety-one hips in seventy-one patients were
      evaluated radiographically for evidence of progression of femoral head collapse
      at a minimum of two years, and a mean of three years, postoperatively. We defined
      conversion to a total hip arthroplasty and progression of femoral head collapse
      as the failure end points, and we analyzed the association of the acetabular
      center-edge angle of Wiberg, the area and laterality of the lesion, the amount of
      preoperative collapse of the femoral head, and the etiology of the osteonecrosis
      with the likelihood of failure. RESULTS: Forty-eight (24%) of the 200 hips had
      undergone conversion to a total hip arthroplasty at the time of the final
      clinical follow-up. In addition, 15% (fourteen) of the ninety-one hips with
      sufficient radiographic follow-up demonstrated progression of femoral head
      collapse at the time of the final radiographic examination. Of the hips with a
      center-edge angle of </=30 degrees , 55% (of those with sufficient radiographic
      follow-up) demonstrated progressive collapse and 45% were converted to a total
      hip arthroplasty. In contrast, of the hips with a center-edge angle of >30
      degrees , 10% had progressive collapse (p = 0.002) and 6% were converted to a
      total hip arthroplasty (p < 0.001). Neither the etiology nor the size of the
      lesion was significantly correlated with progression of collapse or conversion to
      a total hip arthroplasty. CONCLUSIONS: Patients with osteonecrosis of the femoral
      head and a suboptimal center-edge angle of the hip are at substantial risk for
      progression of femoral head collapse and conversion to a total hip arthroplasty
      following free vascularized fibular grafting. An estimation of the degree of hip
      dysplasia should be included in the preoperative assessment of patients with
      osteonecrosis of the femoral head for prognostic and possibly surgical planning
      purposes.

PMID- 17015592
TI  - The influence of income and race on total knee arthroplasty in the United States.
AB  - BACKGROUND: The associations among income, total knee arthroplasty, and
      underlying rates of knee osteoarthritis are not well understood. We studied
      whether high-income Medicare recipients are more likely to have a knee
      arthroplasty and less likely to suffer from knee osteoarthritis. METHODS: Two
      data sources were used: (1) the 2000 United States Medicare claims data measuring
      the incidence of total knee arthroplasty by race, ethnicity, zip (postal) code
      income, and region (n = 27.5 million) and (2) the National Health and Nutrition
      Examination Survey (NHANES III) for individuals with an age of sixty years or
      more (n = 1926) with radiographic and clinical evidence of osteoarthritis.
      Logistic regression methods were used to adjust for covariates. RESULTS: At the
      national level, age-adjusted rates of total knee arthroplasty in the high-income
      quintile were no higher than those in the low-income group (odds ratio, 0.98; 95%
      confidence interval, 0.96 to 1.00). Within regions, access to care was better for
      high-income groups (odds ratio, 1.19; 95% confidence interval, 1.17 to 1.22).
      Racial disparities in arthroplasty were significant (p < 0.001); the odds ratio
      was 0.36 (95% confidence interval, 0.34 to 0.38) for black men and 0.45 (95%
      confidence interval, 0.41 to 0.49) for Asian women. There was no evidence of an
      income gradient for most clinical and radiographic measures of arthritis. The
      exception was a significant negative association between income and pain on
      passive motion (p < 0.05). CONCLUSIONS: High-income Medicare enrollees are no
      less likely to have osteoarthritis than low-income enrollees but have somewhat
      better access to care. Racial disparities are more important than those that are
      attributable to socioeconomic status.

PMID- 17015593
TI  - Comparison of bulb syringe and pulsed lavage irrigation with use of a
      bioluminescent musculoskeletal wound model.
AB  - BACKGROUND: Despite the fact that wound irrigation is a common surgical
      procedure, there are many variables, including delivery device, irrigant type,
      and fluid volume, that have yet to be optimized. The purpose of this study was to
      compare, with use of transgenic bioluminescent bacteria and standard quantitative
      microbiological methods, the efficacy of pulsed lavage and bulb syringe
      irrigation in reducing wound bacterial counts. METHODS: A caprine model of a
      complex, contaminated musculoskeletal wound was developed with use of a
      bioluminescent strain of Pseudomonas aeruginosa that can be quantified.
      Luminescent activity was recorded as relative luminescent units with use of a
      photon-counting camera six hours after the wound was created and inoculated.
      Twelve goats were randomly assigned to either the pulsed lavage group or the bulb
      syringe irrigation group. Each wound was irrigated with normal saline solution in
      3-L increments for a total of 9 L and was imaged after each 3-L increment. In
      addition, quantitative culture samples were obtained from different tissues
      within the wound before and after irrigation. RESULTS: Pulsed lavage decreased
      the amount of relative luminescent units by 52%, 64%, and 70% at 3, 6, and 9 L,
      respectively. The bulb syringe irrigation reduced the amount of relative
      luminescent units by 33%, 44%, and 51% at these same time-points. Significant
      differences in luminescence were noted between the two groups after both 6 and 9
      L of irrigation (p < or = 0.04). The correlation coefficients between relative
      luminescent units and quantitative cultures for the condition before irrigation
      and after irrigation were r = 0.96 and 0.83, respectively. CONCLUSIONS: Pulsed
      lavage was more effective than bulb syringe irrigation in reducing bacterial
      luminescence after both 6 and 9 L of irrigation. Both device and volume effects
      can be demonstrated with use of this model. Bioluminescent bacteria provide a
      method to visualize bacterial distribution and to quantify the bacteria in a
      wound. CLINICAL RELEVANCE: Pulsed lavage is a more effective and efficient method
      of irrigation to remove bacteria in a complex musculoskeletal wound. In the model
      we used, pulsed lavage irrigation with 3 L of saline solution resulted in a
      reduction of approximately the same amount of bacteria as did irrigation with 9 L
      with use of a bulb syringe.

PMID- 17015594
TI  - Causes of intoeing gait in children with cerebral palsy.
AB  - BACKGROUND: Intoeing is a frequent gait problem in children with cerebral palsy.
      It is essential to determine the cause(s) of intoeing when surgical intervention
      is being planned. The purpose of this study was to evaluate the prevalence of
      various causes of intoeing in children with cerebral palsy and to determine
      whether the causes differ between children with bilateral and those with
      unilateral involvement. METHODS: The cause of intoeing gait was examined
      retrospectively, with use of gait analysis, in 412 children with cerebral palsy
      (587 involved sides). The causes were evaluated separately for the children with
      bilateral involvement (diplegia or quadriplegia) and those with hemiplegia.
      RESULTS: Overall, the most common causes of intoeing were internal hip rotation
      (322 of 587 sides) and internal tibial torsion (296 of 587 sides). Pes varus
      contributed to intoeing of thirty-five of the eighty-two involved limbs of the
      patients with hemiplegia and of forty-two of the 505 limbs of the patients with
      diplegia or quadriplegia. Multiple causes of intoeing were noted in 215 of the
      587 involved limbs, including 176 of the 505 limbs of the patients with bilateral
      involvement and thirty-nine of the eighty-two involved limbs of the patients with
      hemiplegia. The most common causes of intoeing in the subjects with bilateral
      involvement were internal hip rotation (288 of 505), internal tibial torsion (261
      of 505), and internal pelvic rotation (ninety-two of 505). The most common causes
      in the hemiplegic children were internal tibial torsion (thirty-five of eighty
      two), pes varus (thirty-five of eighty-two), internal hip rotation (thirty-four
      of eighty-two), and metatarsus adductus (twenty of eighty-two). CONCLUSIONS: More
      than one-third of children with cerebral palsy have multiple causes of intoeing.
      Pes varus commonly contributes to intoeing by children with hemiplegic cerebral
      palsy but rarely contributes to intoeing by those with diplegia or quadriplegia.
      These findings should be carefully considered prior to surgical correction of the
      intoeing gait of these patients.

PMID- 17015596
TI  - Comminuted radial head fractures treated with a modular metallic radial head
      arthroplasty. Study of outcomes.
AB  - BACKGROUND: Comminuted fractures of the radial head are challenging to treat with
      open reduction and internal fixation. Radial head arthroplasty is an alternative
      treatment with results that compare favorably with those reported after open
      reduction and internal fixation of similar fractures. The purpose of this study
      was to evaluate the two-year outcomes and the rate of recovery of a closely
      followed cohort of patients in whom an unreconstructible radial head fracture had
      been treated with a modular metallic prosthesis. METHODS: Twenty-six patients
      (seventeen female and nine male; mean age, fifty-four years) with an
      unreconstructible comminuted radial head fracture and associated elbow injuries
      were treated with a modular metallic radial head arthroplasty. Patients who had
      presented more than four weeks following the injury or had had the radial head
      arthroplasty as a second-stage or salvage procedure were excluded. Of the twenty
      six patients, twenty-two had an associated elbow dislocation, and thirteen of
      them also had an associated fracture of the coronoid process. Patients were
      prospectively followed at three, six, twelve, and twenty-four months. Self
      reported limb function, general health, range of motion, and isometric strength
      were assessed by an independent observer. RESULTS: Following treatment of the
      injury, significant decreases in self-reported and measured impairments were
      noted over time, with the majority of the recovery occurring by six months and
      little further recovery noted between six and twenty-four months. There were
      slight-to-moderate deficits in the range of motion and strength compared with the
      values on the contralateral, unaffected side. Patient satisfaction was high at
      three months and remained high at two years. All elbow joints remained stable, no
      implant required revision, and there was no evidence of overstuffing of the
      joint. Mild osteoarthritis was seen in five (19%) of the twenty-six patients.
      CONCLUSIONS: An arthroplasty with a modular metallic radial head is a safe and
      effective option for the treatment of unreconstructible radial head fractures
      associated with other elbow injuries. Recovery primarily occurs by six months,
      with minimal additional improvements over the next eighteen months.

PMID- 17015595
TI  - Surface treatment of flexor tendon autografts with carbodiimide-derivatized
      hyaluronic Acid. An in vivo canine model.
AB  - BACKGROUND: Clinical and experimental studies have demonstrated that restrictive
      adhesions and poor digital motion are common complications after extrasynovial
      tendon grafting in an intrasynovial environment. The purpose of this study was to
      test the hypothesis that surface modification of an extrasynovial tendon with use
      of a carbodiimide-derivatized hyaluronic acid-gelatin polymer (cd-HA) improves
      gliding ability and digital function after tendon grafting in a canine model in
      vivo. METHODS: The peroneus longus tendons from both hindpaws of twenty-four dogs
      were harvested and transplanted to replace the flexor digitorum profundus tendons
      in the second and fifth digits of one forepaw. Prior to grafting, one of the
      peroneus longus tendons was coated with cd-HA, which consists of 1% hyaluronic
      acid, 10% gelatin, 0.25% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      hydrochloride (EDC), and 0.25% N-hydroxysuccinimide (NHS), while the other was
      immersed in saline solution only. Eight dogs were killed at one, three, and six
      weeks. Digital normalized work of flexion, tendon gliding resistance, and
      hyaluronic acid quantification (with the hyaluronic acid-binding-protein staining
      technique) were the outcome measures. RESULTS: The normalized work of flexion of
      the tendons treated with cd-HA was significantly lower than that of the saline
      solution-treated controls at each time-point (p < 0.05). The gliding resistance
      of the cd-HA group was significantly lower than that of the saline-solution group
      at three and six weeks (p < 0.05). The ratio between the intensity of staining of
      the cd-HA-treated tendons with that of the saline-solution-treated controls was
      significantly greater at time-0 than at three or six weeks (p < 0.05), but there
      was no significant difference between time-0 and one-week values. CONCLUSIONS:
      Treating the surface of an extrasynovial tendon autograft with a carbodiimide
      derivatized hyaluronic acid-gelatin polymer decreases digital work of flexion and
      tendon gliding resistance in this flexor tendon graft model in vivo. CLINICAL
      RELEVANCE: cd-HA gelatin may provide surgeons with a new and useful method to
      improve the quality of tendon graft surgery.

PMID- 17015597
TI  - Effect of early full weight-bearing after joint injury on inflammation and
      cartilage degradation.
AB  - BACKGROUND: Early full weight-bearing after an acute osteochondral injury avoids
      problems associated with immobility but may also be harmful by amplifying the
      inflammatory response. To investigate these effects, we developed an in vivo
      model of subchondral trauma. METHODS: After an impact injury to the femoral
      condyle, fourteen dogs were randomized to immediate full weight-bearing or to
      four weeks of minimal weight-bearing before full weight-bearing. Synovial fluid
      was sampled by aspiration at one, two, four, eight, twelve, sixteen, twenty, and
      twenty-four weeks. Neutrophils, monocytes, and lymphocytes were enumerated, and
      the concentrations of tumor necrosis factor-alpha, interleukin-10, nitric oxide,
      matrix metalloproteinases, and glycosaminoglycans were measured. RESULTS:
      Compared with the findings for uninjured joints, the synovial fluid from the
      impacted joints of full-weight-bearing dogs had significantly higher peak
      concentrations of neutrophils (p = 0.0006 at one week), mononuclear leukocytes (p
      = 0.001 at four weeks), tumor necrosis factor-alpha (p = 0.001 at one week),
      nitric oxide (p = 0.001 at one week), matrix metalloproteinases (p = 0.008 at one
      week), and glycosaminoglycans (p = 0.002 at four weeks and p = 0.001 at six
      months). The size of the bone bruise correlated with the peak concentrations of
      tumor necrosis factor-alpha (r2= 0.89, p = 0.007; Spearman rank test), matrix
      metalloproteinases (r2= 0.96, p = 0.0004), and glycosaminoglycans (r2= 0.96, p =
      0.0004). However, restriction to minimal weight-bearing for four weeks after the
      injury led to a significant reduction in the synovial fluid concentrations of
      neutrophils (p = 0.007 at one week and p = 0.01 at two weeks), tumor necrosis
      factor-alpha (p = 0.0006 to 0.02 during the first four weeks), nitric oxide (p =
      0.001 to 0.04 during the first four weeks), and matrix metalloproteinases (p =
      0.007 to 0.01 from the second week to the eighth week). In contrast, interleukin
      10 concentrations were significantly higher (p = 0.002 at one week) and
      glycosaminoglycan levels remained at normal levels in animals that were
      restricted from immediate full weight-bearing after the injury. CONCLUSIONS: The
      magnitude of the inflammatory response is proportional to the size of the bone
      bruise. Restriction to minimal weight-bearing for four weeks reduces the
      magnitude of the inflammatory response and the cartilage degradation following
      articular cartilage impact injury. CLINICAL RELEVANCE: Strategies to minimize
      mechanical stress during the early postinjury period may help to preserve
      cartilage integrity and forestall the development of osteoarthritis.

PMID- 17015598
TI  - Cementless total hip arthroplasty with the rectangular titanium Zweymuller stem.
      A concise follow-up, at a minimum of fifteen years, of a previous report.
AB  - Between October 1986 and November 1987, 208 total hip arthroplasties were
      performed with use of the cementless Zweymuller stem and a threaded cup in 200
      consecutive patients. Of 102 patients (108 hips) who were available for follow-up
      at a minimum of 180 months postoperatively, eighty-three (eighty-nine hips) had
      the primary joint replacement still intact. No stem had been revised because of
      aseptic loosening, but we found various degrees of osteolysis around sixteen
      (18%) of the implants. The probability of survival of the stem at fifteen years
      was 0.98 (95% confidence interval, 0.96 to 1.00). The probability of survival of
      the cup was 0.85 (95% confidence interval, 0.79 to 0.91).

PMID- 17015599
TI  - Fracture of the anteromedial facet of the coronoid process.
AB  - BACKGROUND: Fracture of the anteromedial facet of the coronoid was recently
      recognized as a distinct type of coronoid fracture resulting from a varus
      posteromedial rotational injury force. Very few reports are available to help
      guide the management of these injuries. METHODS: Eighteen patients with a
      fracture of the anteromedial facet of the coronoid process were treated over a
      six-year period. Twelve patients were treated for the acute fracture, and six
      were managed after initial treatment elsewhere. All but three patients (two with
      concomitant fracture of the olecranon and one with a second fracture at the base
      of the coronoid) had avulsion of the origin of the lateral collateral ligament
      complex from the lateral epicondyle. The initial treatment was operative in
      fifteen patients and nonoperative in three. The coronoid fracture was secured
      with a plate applied to the medial surface of the coronoid in nine patients, a
      screw in one patient, and sutures in one patient. It was not repaired in the
      remaining seven patients. RESULTS: At the final evaluation, an average of twenty
      six months after the injury, six patients had malalignment of the anteromedial
      facet of the coronoid with varus subluxation of the elbow, which was due to the
      fact that the fracture had not been specifically treated in four patients and to
      loss of fracture fixation in two patients. All six had development of arthrosis
      and a fair or poor result according to the system of Broberg and Morrey. The
      remaining twelve patients had good or excellent elbow function. CONCLUSIONS:
      Anteromedial fractures of the coronoid are associated with either subluxation or
      complete dislocation of the elbow in most patients. Secure fixation of the
      coronoid fracture usually restores good elbow function.

PMID- 17015601
TI  - High placement of noncemented acetabular components in revision total hip
      arthroplasty. A concise follow-up, at a minimum of fifteen years, of a previous
      report.
AB  - We previously reported the average ten-year results associated with the use of
      porous-coated noncemented acetabular shells that were placed at a high hip center
      at the time of revision total hip arthroplasty in thirty-four patients (thirty
      six hips) with severe acetabular bone loss. We now report the average 16.8-year
      results for twenty-one patients (twenty-three hips). Of the original cohort of
      forty-four patients (forty-six hips), thirty-nine patients (forty-one hips; 89%)
      retained the shell. Two shells (4.3%) were revised because of aseptic loosening,
      and three (6.5%) were revised because of infection. Six femoral components were
      revised because of femoral osteolysis, and seven were revised because of aseptic
      loosening without osteolysis. On the basis of our results after an average
      duration of follow-up of 16.8 years, we believe that the placement of an
      uncemented acetabular component at a high hip center continues to be an excellent
      technique for revision total hip arthroplasty in selected patients with severe
      acetabular bone loss.

PMID- 17015600
TI  - Patellar complications following distal femoral replacement after bone tumor
      resection.
AB  - BACKGROUND: Patellar complications following endoprosthetic reconstruction can
      occur as a result of anatomic, physiologic, and surgical reasons. Patellar
      impingement on tibial polyethylene is a complication of distal femoral
      replacement, and it is frequently related to inaccurate restoration of the joint
      line and to soft-tissue contracture. The purpose of our study was to determine
      the prevalence and type of patellar complications following distal femoral
      replacements after excisions of bone tumors. METHODS: The results of
      reconstruction with use of a rotating-hinge endoprosthesis following excision of
      a distal femoral tumor in forty-three patients were retrospectively reviewed.
      Patients were followed clinically and radiographically for a minimum of forty
      eight months or until death. Pain status, functional scores, and the range of
      motion were determined from a prospectively maintained database. The ratio of the
      patellar tendon length to the height of the patellar tendon insertion, as
      described by Insall and Salvati, was calculated. In addition, we attempted to
      determine whether the position of the patella was associated with anterior knee
      pain or with the functional scores derived with use of the International Society
      of Limb Salvage (ISOLS) scoring system. RESULTS: Thirty-five patellar
      complications, including eleven cases of impingement, occurred in twenty-seven
      patients (63%). We found no difference, on the basis of our sample size, with
      regard to the presence of patellar pain, the range of motion, or the Insall
      Salvati ratio between the patients with and those without impingement. The ratio
      of the patellar tendon length to the height of the patellar tendon insertion
      averaged 0.9 in the group with impingement and 1.4 in the group without
      impingement (p = 0.07). The ISOLS score averaged 21.2 points in the group with
      impingement compared with 24.2 points in the group without impingement (p =
      0.01). Patella baja occurred in nine patients. The average ISOLS score (and
      standard deviation) was 20.1 +/- 4.4 points for the patients with patella baja
      compared with 24.8 +/- 3.9 points in the group with a normal patellar position (p
      = 0.004). Patellar fracture occurred in two patients, and osteonecrosis occurred
      in two patients. These patients were treated nonoperatively. CONCLUSIONS:
      Patellar complications are common after distal femoral resection and
      endoprosthetic reconstruction. Patellar impingement on the polyethylene tibial
      bearing surface is a more common and important complication of distal femoral
      replacement than has been reported to date. Patella baja is also a relatively
      common complication, which has a negative impact on knee function.

PMID- 17015602
TI  - Stress injuries of the calcaneus detected with magnetic resonance imaging in
      military recruits.
AB  - BACKGROUND: Calcaneal stress injuries are fairly common overuse injuries in
      military recruits and athletes. We assessed the anatomic distribution, nature,
      and healing of calcaneal stress injuries in a group of military recruits.
      METHODS: Military recruits who underwent magnetic resonance imaging for the
      evaluation of exercise-induced ankle and/or heel pain were identified from the
      medical archives. The magnetic resonance images, plain radiographs, and medical
      records of these patients were evaluated with regard to fracture type and the
      natural history of the injury. RESULTS: Over ninety-six months, magnetic
      resonance imaging revealed calcaneal stress injuries in thirty recruits in a
      population with a total exposure time of 117,149 person-years, yielding an
      incidence of 2.6 (95% confidence interval, 1.6 to 3.4) per 10,000 person-years.
      Four patients exhibited a bilateral injury. Of the thirty-four injuries, nineteen
      occurred in the posterior part of the calcaneus, six occurred in the middle part
      of the calcaneus, and nine occurred in the anterior part of the calcaneus, with
      79% occurring in the upper region and 21% occurring in the lower region. The
      calcaneus alone was affected in twelve cases. In twenty-two cases, stress injury
      was also present in one or several other tarsal bones. A distinct association
      emerged between injuries of the different parts of the calcaneus and stress
      injuries in the surrounding bones. In only 15% of the patients was the stress
      injury visible on plain radiographs. With the numbers available, there were no
      significant differences between the patients with calcaneal stress injuries and
      unaffected recruits with regard to age, height, weight, body mass index, or
      physical fitness. CONCLUSIONS: The majority of stress injuries of the calcaneus
      occur in the posterior part of the bone, but a considerable proportion can also
      be found in the middle and anterior parts. To obtain a diagnosis, magnetic
      resonance imaging is warranted if plain radiography does not show abnormalities
      in a physically active patient with exercise-induced pain in the ankle or heel.

PMID- 17015603
TI  - Computed radiographic measurement of limb-length discrepancy. Full-length
      standing anteroposterior radiograph compared with scanogram.
AB  - BACKGROUND: Although a scanogram is commonly used to measure limb-length
      discrepancy, there are several potential pitfalls associated with this imaging
      technique. The purpose of the present study was to evaluate the results obtained
      with use of a full-length standing anteroposterior radiograph of the lower
      extremities and to compare them with those obtained with use of a scanogram. Both
      imaging studies were performed using computed radiography. METHODS: One hundred
      and eleven patients with limb-length discrepancy had a full-length standing
      anteroposterior radiograph and a scanogram made on the same day. The patients
      included seventy-nine children and thirty-two adults in whom the discrepancy was
      secondary to trauma (55%), congenital shortening (18%), Blount disease (14%), or
      another cause (13%). Limb length and limb-length discrepancy were measured
      utilizing both imaging studies. The agreement between the standing
      anteroposterior radiograph and the scanogram was assessed with use of the
      correlation coefficient r, and the limits of agreement between the two imaging
      studies were assessed. RESULTS: An average magnification of 4.6% (3.3 cm) was
      observed in association with the measurement of lower extremity length with use
      of the full-length standing anteroposterior radiograph. The mean difference in
      limb-length-discrepancy measurements between the two techniques was 0.5 cm, and
      the limits of agreement (that is, the mean plus or minus two standard deviations)
      were 0.5 to 1.5 cm. When the limb-length discrepancy on the standing
      anteroposterior radiograph was compared with that on the scanogram, the
      correlation coefficient r was 0.96. A difference of >0.5 cm between the limb
      length discrepancy measured on the standing radiograph and that measured on the
      scanogram was associated with a mechanical axis deviation of >2 cm. Remaining
      variables, including age, gender, etiology, and scanogram ruler inclination, did
      not correlate with a difference in the measurement of limb-length discrepancy
      with use of these two imaging studies. CONCLUSIONS: The measurement of limb
      length discrepancy on a standing anteroposterior radiograph was very similar to
      that on a scanogram, especially in the absence of substantial mechanical axis
      deviation. These findings support the use of a standing anteroposterior
      radiograph of the lower extremities as the initial imaging study for patients
      presenting with unequal limb lengths. This approach allows for a more
      comprehensive radiographic evaluation of the lower extremity, including deformity
      analysis, while reducing the expense and radiation exposure as compared with the
      use of additional imaging studies for the assessment of limb-length discrepancy.

PMID- 17015604
TI  - Superior mesenteric artery syndrome following spinal deformity correction.
AB  - BACKGROUND: Superior mesenteric artery syndrome is a known complication
      associated with the correction of spinal deformity. Recent investigations of this
      disorder have focused on patient height and weight. We are not aware of any
      published study examining the degree of deformity, type of curve, or magnitude of
      correction, and to our knowledge all of the reported literature on this syndrome
      lacks control data. The purpose of this study was to examine the relationship
      between the correction of spinal deformity and the development of superior
      mesenteric artery syndrome in patients with scoliosis. Our hypothesis was that
      greater correction of spinal deformity would increase the risk of the development
      of superior mesenteric artery syndrome. METHODS: A case-control study was
      performed over a five-year period. The primary outcome measure was the
      development of superior mesenteric artery syndrome. The predictor variables that
      were considered included demographic characteristics; preoperative height,
      weight, and body mass index; aspects of the deformity, including curve magnitude,
      Lenke curve classification, and correction; and operative factors, including
      surgical approach, estimated blood loss, and the presence of operative
      hypotension. RESULTS: A review of the records on 364 surgical procedures for
      scoliosis identified seventeen cases of superior mesenteric artery syndrome.
      Thirty-four subjects who had had surgery for scoliosis but no superior mesenteric
      artery syndrome were randomly selected as controls. Eight of the seventeen
      subjects with superior mesenteric artery syndrome had undergone a two-stage
      procedure (compared with one of the thirty-four controls, p < 0.001), nine of the
      seventeen had had combined anterior and posterior procedures (compared with two
      of the thirty-four controls, p < 0.001), and seven of the seventeen had had a
      thoracoplasty (compared with two of the thirty-four controls, p < 0.001). No
      significant differences were noted between the groups with regard to demographic
      factors. Compared with the controls, the patients in whom superior mesenteric
      artery syndrome developed were shorter (by a mean of 7.1 cm, p = 0.03), weighed
      less (by a mean of 11.5 kg, p = 0.001), had a lower body mass index (p = 0.003),
      had a greater minimal thoracic curve magnitude achieved by bending (a mean of 12
      degrees greater [45 degrees for subjects with superior mesenteric artery syndrome
      and 33 degrees for controls], p = 0.015), had a lower percent correction of the
      thoracic curve on bending (a mean of 11% lower, p = 0.025), and had more lumbar
      lateralization (88%, compared with 61% in the control group, had a Lenke lumbar
      modifier of B or C instead of A, p = 0.008). Multivariate logistic regression
      analysis identified a staged procedure (odds ratio, 31.0), the lumbar modifier
      (odds ratio, 9.06), body mass index (odds ratio, 7.75), and thoracic stiffness
      (odds ratio, 6.67) as the most predictive of the development of superior
      mesenteric artery syndrome. CONCLUSIONS: Preoperative identification of the risk
      factors described above in conjunction with preoperative nutritional maximization
      should be considered in order to limit the prevalence of superior mesenteric
      artery syndrome in patients undergoing surgical correction of spinal deformity.

PMID- 17015605
TI  - Two-part surgical neck fractures of the proximal part of the humerus. A
      biomechanical evaluation of two fixation techniques.
AB  - BACKGROUND: Successful internal fixation of fractures of the surgical neck of the
      humerus can be difficult to achieve because of osteopenia of the proximal aspect
      of the humerus. The purpose of this study was to compare the biomechanical
      stability of a proximal humeral intramedullary nail and a locking plate for the
      treatment of a comminuted two-part fracture of the surgical neck in a human
      cadaver model. METHODS: Twenty-four cadaveric humeri were instrumented with use
      of either a titanium proximal humeral nail (PHN) or a 3.5-mm locking compression
      plate for the proximal part of the humerus (LCP-PH). The specimens were matched
      by bone mineral density and were separated into four experimental groups with six
      humeri in each: PHN bending, LCP-PH bending, PHN torsion, or LCP-PH torsion.
      Comminuted fractures of the surgical neck were simulated by excising a 10-mm
      wedge of bone. Bending specimens were cyclically loaded from 0 to 7.5 Nm of varus
      bending moment at the fracture site. Torsion specimens were cyclically loaded to
      +/-2 Nm of axial torque. The mean and maximum displacement in bending, mean and
      maximum angular rotation in torsion, and stiffness of the bone-implant constructs
      were compared. RESULTS: In bending, the LCP-PH group demonstrated significantly
      less mean displacement of the distal fragment than did the PHN group over 5000
      cycles (p = 0.002). In torsion, the LCP-PH group demonstrated significantly less
      mean angular rotation than did the PHN group over 5000 cycles (p = 0.04). A
      significant number of specimens in the PHN group failed prior to reaching 5000
      cycles (p = 0.04). The LCP-PH implant created a significantly stiffer bone
      implant construct than did the PHN implant (p = 0.007). CONCLUSIONS: The LCP
      proximal humeral plate demonstrated superior biomechanical characteristics
      compared with the proximal humeral nail when tested cyclically in both
      cantilevered varus bending and torsion. The rate of early failure of the proximal
      humeral nail could reflect the high moment transmitted to the locking proximal
      screw-bone interface in this implant. CLINICAL RELEVANCE: The high failure rate
      in torsion of the proximal humeral nail-bone construct is concerning, and, with
      relatively osteoporotic bone and early motion, the results could be poor.

PMID- 17015606
TI  - Bilateral exercise-induced compartment syndrome of the thigh and leg associated
      with massive heterotopic ossification. A case report.

PMID- 17015607
TI  - Hoffa fragment associated with a femoral shaft fracture. A case report.

PMID- 17015608
TI  - Tuberculous spondylitis and salmonella mycotic aneurysm in an immunocompromised
      patient. A case report.

PMID- 17015609
TI  - Complications of total shoulder arthroplasty.

PMID- 17015610
TI  - AOA Professionalism Guiding Leadership.

PMID- 17015611
TI  - Level-I orthopaedic trauma care: a model for longevity.

PMID- 17015612
TI  - Posterior short-segment instrumentation and fusion provides better results than
      combined anterior plus posterior stabilization for mid-lumbar (L2 to L4) burst
      fractures.

PMID- 17015613
TI  - Initially asymptomatic meniscal lesions of the knee were later associated with
      complaints of pain, stiffness, and impaired function but severity was low.

PMID- 17015614
TI  - Posterior spinal fusion was not improved by supplemental bone graft in adolescent
      idiopathic scoliosis.

PMID- 17015615
TI  - What's new in orthopaedic research.

PMID- 17015616
TI  - Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by
      BMP4 and its antagonist Gremlin.
AB  - Skeletal muscle side population (SP) cells are thought to be "stem"-like cells.
      Despite reports confirming the ability of muscle SP cells to give rise to
      differentiated progeny in vitro and in vivo, the molecular mechanisms defining
      their phenotype remain unclear. In this study, gene expression analyses of human
      fetal skeletal muscle demonstrate that bone morphogenetic protein 4 (BMP4) is
      highly expressed in SP cells but not in main population (MP) mononuclear muscle
      derived cells. Functional studies revealed that BMP4 specifically induces
      proliferation of BMP receptor 1a-positive MP cells but has no effect on SP cells,
      which are BMPR1a-negative. In contrast, the BMP4 antagonist Gremlin, specifically
      up-regulated in MP cells, counteracts the stimulatory effects of BMP4 and
      inhibits proliferation of BMPR1a-positive muscle cells. In vivo, BMP4-positive
      cells can be found in the proximity of BMPR1a-positive cells in the interstitial
      spaces between myofibers. Gremlin is expressed by mature myofibers and
      interstitial cells, which are separate from BMP4-expressing cells. Together,
      these studies propose that BMP4 and Gremlin, which are highly expressed by human
      fetal skeletal muscle SP and MP cells, respectively, are regulators of myogenic
      progenitor proliferation.

PMID- 17015617
TI  - SHP-2 activates signaling of the nuclear factor of activated T cells to promote
      skeletal muscle growth.
AB  - The formation of multinucleated myofibers is essential for the growth of skeletal
      muscle. The nuclear factor of activated T cells (NFAT) promotes skeletal muscle
      growth. How NFAT responds to changes in extracellular cues to regulate skeletal
      muscle growth remains to be fully defined. In this study, we demonstrate that
      mice containing a skeletal muscle-specific deletion of the tyrosine phosphatase
      SHP-2 (muscle creatine kinase [MCK]-SHP-2 null) exhibited a reduction in both
      myofiber size and type I slow myofiber number. We found that interleukin-4, an
      NFAT-regulated cytokine known to stimulate myofiber growth, was reduced in its
      expression in skeletal muscles of MCK-SHP-2-null mice. When SHP-2 was deleted
      during the differentiation of primary myoblasts, NFAT transcriptional activity
      and myotube multinucleation were impaired. Finally, SHP-2 coupled myotube
      multinucleation to an integrin-dependent pathway and activated NFAT by
      stimulating c-Src. Thus, SHP-2 transduces extracellular matrix stimuli to
      intracellular signaling pathways to promote skeletal muscle growth.

PMID- 17015618
TI  - Kidney failure in mice lacking the tetraspanin CD151.
AB  - The tetraspanin CD151 is a cell-surface molecule known for its strong lateral
      interaction with the laminin-binding integrin alpha3beta1. Patients with a
      nonsense mutation in CD151 display end-stage kidney failure associated with
      regional skin blistering and sensorineural deafness, and mice lacking the
      integrin alpha3 subunit die neonatally because of severe abnormalities in the
      lung and kidney epithelia. We report the generation of Cd151-null mice that
      recapitulate the renal pathology of human patients, i.e., with age they develop
      massive proteinuria caused by focal glomerulosclerosis, disorganization of the
      glomerular basement membrane, and tubular cystic dilation. However, neither skin
      integrity nor hearing ability are impaired in the Cd151-null mice. Furthermore,
      we generated podocyte-specific conditional knockout mice for the integrin alpha3
      subunit that show renal defects similar to those in the Cd151 knockout mice. Our
      results support the hypothesis that CD151 plays a key role in strengthening
      alpha3beta1-mediated adhesion in podocytes.

PMID- 17015620
TI  - Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.
AB  - Epithelial cells are typically arranged in a honeycomb-like pattern, minimizing
      their cell-cell contact areas, which suggests that some tension operates for
      shaping of the cell boundaries. However, the molecular mechanisms that generate
      such tension remain unknown. We found that Tuba, which is a Cdc42-specific GEF,
      was concentrated at the apical-most region of cell junctions in simple epithelia
      via its interaction with ZO-1. RNAi-mediated depletion of Tuba altered the
      geometrical configuration of cell junctions, resulting in a curved and slack
      appearance. At the subcellular level, Tuba inactivation modified the assembly
      pattern of junctional F-actin and E-cadherin. Tuba RNAi also retarded cell
      junction formation in calcium-switch experiments. Suppression of Cdc42 activity
      or depletion of N-WASP, which is an effector of Cdc42, mimicked the effects of
      Tuba depletion. Conversely, overexpression of dominant-active Cdc42 or N-WASP
      enhanced the junction formation of Tuba-depleted cells. These results suggest
      that Tuba controls the shaping of cell junctions through the local activation of
      Cdc42 and its effectors.

PMID- 17015619
TI  - Role of FIP200 in cardiac and liver development and its regulation of TNFalpha
      and TSC-mTOR signaling pathways.
AB  - Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been
      shown to regulate diverse cellular functions such as cell size, proliferation,
      and migration in vitro. However, the function of FIP200 in vivo has not been
      investigated. We show that targeted deletion of FIP200 in the mouse led to
      embryonic death at mid/late gestation associated with heart failure and liver
      degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase
      activation and cell size as a result of increased tuberous sclerosis complex
      function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart
      and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver
      cells showed increased apoptosis and reduced c-Jun N-terminal kinase
      phosphorylation in response to tumor necrosis factor (TNF) alpha stimulation,
      which might be mediated by FIP200 interaction with apoptosis signal-regulating
      kinase 1 (ASK1) and TNF receptor-associated factor 2 (TRAF2), regulation of TRAF2
      ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that
      FIP200 functions as a regulatory node to couple two important signaling pathways
      to regulate cell growth and survival during mouse embryogenesis.

PMID- 17015621
TI  - Kinesin-13s form rings around microtubules.
AB  - Kinesin is a superfamily of motor proteins that uses the energy of adenosine
      triphosphate hydrolysis to move and generate force along microtubules. A notable
      exception to this general description is found in the kinesin-13 family that
      actively depolymerizes microtubules rather than actively moving along them. This
      depolymerization activity is important in mitosis during chromosome segregation.
      It is still not fully clear by which mechanism kinesin-13s depolymerize
      microtubules. To address this issue, we used electron microscopy to investigate
      the interaction of kinesin-13s with microtubules. Surprisingly, we found that
      proteins of the kinesin-13 family form rings and spirals around microtubules.
      This is the first report of this type of oligomeric structure for any kinesin
      protein. These rings may allow kinesin-13s to stay at the ends of microtubules
      during depolymerization.

PMID- 17015622
TI  - BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein.
AB  - Transforming growth factor beta1 (TGFbeta1), an important regulator of cell
      behavior, is secreted as a large latent complex (LLC) in which it is bound to its
      cleaved prodomain (latency-associated peptide [LAP]) and, via LAP, to latent
      TGFbeta-binding proteins (LTBPs). The latter target LLCs to the extracellular
      matrix (ECM). Bone morphogenetic protein 1 (BMP1)-like metalloproteinases play
      key roles in ECM formation, by converting precursors into mature functional
      proteins, and in morphogenetic patterning, by cleaving the antagonist Chordin to
      activate BMP2/4. We provide in vitro and in vivo evidence that BMP1 cleaves LTBP1
      at two specific sites, thus liberating LLC from ECM and resulting in consequent
      activation of TGFbeta1 via cleavage of LAP by non-BMP1-like proteinases. In mouse
      embryo fibroblasts, LAP cleavage is shown to be predominantly matrix
      metalloproteinase 2 dependent. TGFbeta1 is a potent inducer of ECM formation and
      of BMP1 expression. Thus, a role for BMP1-like proteinases in TGFbeta1 activation
      completes a novel fast-forward loop in vertebrate tissue remodeling.

PMID- 17015623
TI  - Extracellular matrix-mediated tissue remodeling following axial movement of
      teeth.
AB  - Tooth eruption is a multifactorial process involving movement of existing tissues
      and formation of new tissues coordinated by a complex set of genetic events. We
      have used the model of the unopposed rodent molar to study morphological and
      genetic mechanisms involved in axial movement of teeth. Following extraction of
      opposing upper molars, lower molars supererupted by 0.13 mm. Labeled tissue
      sections revealed significant amounts of new bone and cementum apposition at the
      root apex of the unopposed side following supereruption for 12 days. Newly
      apposited cementum and alveolar bone layers were approximately 3-fold thicker in
      the experimental vs the control group, whereas periodontal ligament width was
      maintained. Tartrate-resistant acid phosphatase staining indicated bone
      resorption at the mesial alveolar walls of unopposed molars and provided in
      tandem with new bone formation at the distal alveolar walls an explanation for
      the distal drift of molars in this model. Microarray analysis and
      semiquantitative RT-PCR demonstrated a significant increase in collagen I,
      integrin beta5, and SPARC gene expression as revealed by comparison between the
      unopposed molar group and the control group. Immunohistochemical verification
      revealed increased levels of integrin beta5 and SPARC labeling in the periodontal
      ligament of the unopposed molar. Together our findings suggest that posteruptive
      axial movement of teeth was accomplished by significant formation of new root
      cementum and alveolar bone at the root apex in tandem with upregulation of
      collagen I, integrin beta5, and SPARC gene expression.

PMID- 17015624
TI  - Hemicentins assemble on diverse epithelia in the mouse.
AB  - Hemicentins are recently described extracellular matrix (ECM) proteins with a
      single ortholog in C. elegans that assembles into discrete tracks constricting
      broad regions of epithelial cell contact into adhesive and flexible line-shaped
      junctions. There are two highly conserved hemicentin genes in most vertebrate
      species; however, nothing is known about the function or distribution of
      vertebrate hemicentins. To determine the distribution of vertebrate hemicentins,
      we used a polyclonal antibody to stain mouse tissue and showed that hemicentins
      are found in the pericellular ECM of epithelial cells in a number of tissues
      including embryonic trophectoderm and adult skin and tongue, in addition to the
      ECM of some, but not all, blood vessels. Hemicentins also assemble on multiple
      epithelia in the eye, including cornea, lens, and retina. The pericellular
      localization of vertebrate hemicentins on epithelia and other cell surfaces
      suggests that vertebrate hemicentins, like their nematode counterpart, are
      secreted ECM proteins likely to have a role in the architecture of adhesive and
      flexible cell junctions, particularly in tissues subject to significant amounts
      of mechanical stress.

PMID- 17015625
TI  - Functional analysis of DNA gyrase mutant enzymes carrying mutations at position
      88 in the A subunit found in clinical strains of Mycobacterium tuberculosis
      resistant to fluoroquinolones.
AB  - We investigated the enzymatic efficiency and inhibition by quinolones of
      Mycobacterium tuberculosis DNA gyrases carrying the previously described GyrA
      G88C mutation and the novel GyrA G88A mutation harbored by two multidrug
      resistant clinical strains and reproduced by site-directed mutagenesis.
      Fluoroquinolone MICs and 50% inhibitory concentrations for both mutants were 2-
      to 43-fold higher than for the wild type, demonstrating that these mutations
      confer fluoroquinolone resistance in M. tuberculosis.

PMID- 17015626
TI  - High prevalence of the K65R mutation in human immunodeficiency virus type 1
      subtype C isolates from infected patients in Botswana treated with didanosine
      based regimens.
AB  - We analyzed the reverse transcriptase genotypes of human immunodeficiency virus
      type 1 subtype C viruses isolated from 23 patients in Botswana treated with
      didanosine-based regimens. The K65R mutation was selected either alone or
      together with the Q151M, S68G, or F116Y substitution in viruses from seven such
      individuals. The results of in vitro passage experiments were consistent with an
      apparent increased propensity of subtype C viruses to develop the K65R
      substitution.

PMID- 17015627
TI  - Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in
      experimental murine cutaneous leishmaniasis.
AB  - Glibenclamide reduced the rate of lesion growth in BALB/c mice infected with
      Leishmania (Leishmania) mexicana, the effect was dose dependent, and the highest
      dose proved more effective than glucantime. Cross-resistance to glucantime was
      found in animals infected with a glibenclamide-resistant line, but combined
      therapy reduced lesion progression even in the glibenclamide-resistant strain.

PMID- 17015628
TI  - Efficacy of caspofungin against Aspergillus flavus, Aspergillus terreus, and
      Aspergillus nidulans.
AB  - The echinocandin caspofungin is a potent inhibitor of the activity of 1,3-beta-D
      glucan synthase from Aspergillus flavus, Aspergillus terreus, and Aspergillus
      nidulans. In murine models of disseminated infection, caspofungin prolonged
      survival and reduced the kidney fungal burden. Caspofungin was at least as
      effective as amphotericin B against these filamentous fungi in vivo.

PMID- 17015629
TI  - A new evolutionary variant of the streptogramin A resistance protein, Vga(A)LC,
      from Staphylococcus haemolyticus with shifted substrate specificity towards
      lincosamides.
AB  - We found a new variant of the streptogramin A resistance gene, vga(A)LC, in
      clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and
      clindamycin but susceptible to erythromycin and in which no relevant lincosamide
      resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A)
      at the protein level by seven amino acid substitutions, was present exclusively
      in S. haemolyticus strains resistant to both lincosamides and streptogramin A
      (LS(A) phenotype). Antibiotic resistance profiles of the ATP-binding cassette
      (ABC) proteins Vga(A)(LC) and Vga(A) in the antibiotic-susceptible host S. aureus
      RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both
      lincosamides and streptogramin A, while Vga(A) conferred significant resistance
      to streptogramin A only. Detailed analysis of the seven amino acid substitutions,
      distinguishing the two related ABC proteins with different substrate
      specificities, identified the substrate-recognizing site: four clustered
      substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP
      binding cassettes altered the substrate specificity and constituted the
      lincosamide-streptogramin A resistance phenotype. A transport experiment with
      radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance
      in S. haemolyticus was identical to that of the reported macrolide-streptogramin
      B resistance conferred by Msr(A).

PMID- 17015630
TI  - Efficacy of high doses of levofloxacin in experimental foreign-body infection by
      methicillin-susceptible Staphylococcus aureus.
AB  - Antimicrobial efficacy in orthopedic device infections is diminished because of
      bacterial biofilms which express tolerance to antibiotics. Recently, the use of
      high doses of levofloxacin with rifampin has been recommended for staphylococcal
      infections. In the present study, we evaluated the efficacy of levofloxacin at
      doses of 50 mg/kg/day and 100 mg/kg/day (mimicking the usual and high human doses
      of 500 mg/day and 750 to 1,000 mg/day, respectively) and compared it to that of
      to linezolid, cloxacillin, vancomycin, and rifampin in a rat tissue cage model of
      experimental foreign-body infection by Staphylococcus aureus. The antimicrobial
      efficacy in vitro (by MIC, minimum bactericidal concentration, and kill curves)
      for logarithmic- and stationary-phase bacteria was compared with the in vivo
      efficacy. In vitro bactericidal activity at clinically relevant concentrations
      was reached by all drugs except rifampin and linezolid in the log-phase studies
      but only by levofloxacin in the stationary-phase studies. The bacterial count
      decreases from in vivo tissue cage fluids (means) for levofloxacin at 50 and 100
      mg/kg/day, rifampin, cloxacillin, vancomycin, linezolid, and controls,
      respectively, were: -1.24, -2.26, -2.1, -1.56, -1.47, -1.15, and 0.33 (all groups
      versus controls, P < 0.05). Levofloxacin at 100 mg/kg/day (area under the
      concentration-time curve/MIC ratio, 234) was the most active therapy (P = 0.03
      versus linezolid). Overall, in vivo efficacy was better predicted by stationary
      phase studies, in which it reached a high correlation coefficient even if the
      rifampin group was excluded (r = 0.96; P < 0.05). Our results, including in vitro
      studies with nongrowing bacteria, pharmacodynamic parameters, and antimicrobial
      efficacy in experimental infection, provide good evidence to support the use of
      levofloxacin at high doses (750 to 1,000 mg/day), as recently recommended for
      treating patients with orthopedic prosthesis infections.

PMID- 17015631
TI  - Antifungal susceptibilities of the species of the Pseudallescheria boydii
      complex.
AB  - Eighty-four isolates belonging to eight species that constitute the
      Pseudallescheria boydii complex were tested against 11 antifungal agents by using
      the microdilution method. There were significant differences among the species,
      with Scedosporium aurantiacum being the most resistant. In general, voriconazole
      was the most active drug, followed by posaconazole.

PMID- 17015632
TI  - In vitro activities of the novel oxazolidinones DA-7867 and DA-7157 against
      rapidly and slowly growing mycobacteria.
AB  - DA-7867 and DA-7157 are oxazolidinones active against pathogenic aerobic
      actinomycetes including Nocardia spp. and Mycobacterium tuberculosis. However,
      the activity of these drugs against nontuberculous mycobacterium (NTM) species is
      not known. In this work, we compared the susceptibilities of 122 clinical
      isolates and 29 reference species of both rapidly growing and slowly growing
      mycobacteria to linezolid, DA-7867, and DA-7157 by the broth microdilution
      method. The MICs for 50 and 90% of the strains tested (MIC50s and MIC90s,
      respectively) of DA-7867 and DA-7157 were lower than those of linezolid. In all
      of the cases, a MIC90 of <8 microg/ml was observed for all of the species tested
      in both groups of NTM. For M. kansasii and M. marinum isolates, the MIC90s of
      both DA-7867 and DA-7157 were less than 0.5 microg/ml. These results demonstrate
      the potential of these compounds to treat NTM infections.

PMID- 17015633
TI  - Emergence of multidrug-resistant Klebsiella pneumoniae isolates producing VIM-4
      metallo-beta-lactamase, CTX-M-15 extended-spectrum beta-lactamase, and CMY-4 AmpC
      beta-lactamase in a Tunisian university hospital.
AB  - Klebsiella pneumoniae clinical isolates resistant to carbapenems were recovered
      from 11 patients in the hospital of Sfax, Tunisia. The isolates were closely
      related as shown by pulsed-field gel electrophoresis, and they produced VIM-4
      metallo-enzyme, CTX-M-15 extended-spectrum beta-lactamase, and CMY-4 AmpC enzyme.
      The bla(VIM-4) gene is part of a class 1 integron.

PMID- 17015634
TI  - CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of
      Leishmania major infection favors pathogen persistence.
AB  - Pathogen persistence after clinical cure is a hallmark of many chronic
      infections. Previously, we showed that naturally occurring CD4+CD25+ regulatory T
      (nTreg) cells rapidly accumulate within chronic dermal sites of Leishmania major
      infection where they suppress anti-pathogen CD4+ T cell responses, favor parasite
      persistence and dermal pathology, and consequently control concomitant immunity.
      Here, we postulated that chemokines might direct nTreg cell homing in sites of
      infection and show that CD4+CD25+ nTreg cells, compared with normal CD4+ T cells,
      preferentially express the CCR5 chemokine receptor, which enables them to migrate
      in response to CCR5 ligands in vitro. We show that in contrast to their wild-type
      (WT) counterparts, CCR5-/- CD4+CD25+ nTreg cells resulted in an increased
      magnitude of parasite-specific, interferon gamma-producing CD4+ T cells within
      infection sites, dramatically reduced parasite numbers, and potent resistance to
      infection, a finding consistent with the clinical outcome of infected CCR5-/-
      mice. Interestingly, this resistance was related to an inefficient migration of
      CCR5-/- nTreg cells to infected dermal sites compared with WT nTreg cells. Thus,
      this study shows that CCR5 directs the homing of CD4+CD25+ nTreg cells to L.
      major-infected dermal sites where they promote the establishment of infection and
      long-term survival of the parasite in the immune host.

PMID- 17015637
TI  - Mechanisms linking adenosine A1 receptors and extracellular signal-regulated
      kinase 1/2 activation in human trabecular meshwork cells.
AB  - This study was designed to evaluate the signaling pathways coupling adenosine A1
      receptors and extracellular signal-regulated kinase (ERK) 1 and 2 in human
      trabecular meshwork (HTM) cells. Studies were conducted using cultures of primary
      HTM cells and the HTM-3 cell line. Activation of ERK1/2, location of protein
      kinase C (PKC) isoforms, and matrix metalloproteinase (MMP) secretion were
      determined by Western blotting. In primary HTM cells and the HTM-3 cell line,
      administration of the A1 agonist N6-cyclohexyladenosine (CHA) produced a
      concentration-dependent increase in ERK1/2 activation. This CHA-induced ERK
      activation was blocked by pretreatment with the A1 receptor antagonist 8
      cyclopentyl-1,3-dimethylxanthine or pertussis toxin. Transfection with dominant
      negative N17 Ras produced only a small (31%) decline in CHA-induced ERK
      activation, and the response was not altered by pretreatment with the Src
      tyrosine kinase inhibitor, PP2 [3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H
      pyrazolo[3,4-D] pyrimidin-4-amine], the phosphoinositide kinase-3 inhibitor, LY
      294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], or the A3 receptor
      antagonist, MRS-1191 [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/
      )-dihydropyridine-3,5-dicarboxylate]. Administration of CHA also induced the
      translocation of PKCalpha from the cytosol to the membrane, and pretreatment with
      the phospholipase C (PLC) inhibitor, U73122 [1-[6-[[(17beta)-3-methoxyestra
      1,3,5(10)-trien-17-yl]amino]-hexyl]-1H-pyrrole-2,5-dione], blocked ERK1/2
      activation induced by CHA. Transfection of short interfering RNA targeting
      PKCalpha blocked the CHA-induced ERK1/2 activation and the secretion of MMP-2.
      These results confirm the existence of functional adenosine A1 receptors in the
      trabecular meshwork cells. These receptors are coupled to the activation of
      ERK1/2 through G(i/o) proteins and dependent upon the upstream activation of PLC
      and PKCalpha. These studies provide evidence that adenosine A1 receptor agonists
      increase outflow facility through sequential activation of G(i/o) > PLC >
      PKCalpha > c-Raf > mitogen-activated protein kinase kinase > ERK1/2, leading to
      secretion of MMP-2.

PMID- 17015635
TI  - Rescue of TRAF3-null mice by p100 NF-kappa B deficiency.
AB  - Proper activation of nuclear factor (NF)-kappaB transcription factors is critical
      in regulating fundamental biological processes such as cell survival and
      proliferation, as well as in inflammatory and immune responses. Recently, the NF
      kappaB signaling pathways have been categorized into the canonical pathway, which
      results in the nuclear translocation of NF-kappaB complexes containing p50, and
      the noncanonical pathway, which involves the induced processing of p100 to p52
      and the formation of NF-kappaB complexes containing p52 (Bonizzi, G., and M.
      Karin. 2004. Trends Immunol. 25:280-288). We demonstrate that loss of tumor
      necrosis factor (TNF) receptor-associated factor 3 (TRAF3) results in
      constitutive noncanonical NF-kappaB activity. Importantly, TRAF3-/- B cells show
      ligand-independent up-regulation of intracellular adhesion molecule 1 and
      protection from spontaneous apoptosis during in vitro culture. In addition, we
      demonstrate that loss of TRAF3 results in profound accumulation of NF-kappaB
      inducing kinase in TRAF3-/- cells. Finally, we show that the early postnatal
      lethality observed in TRAF3-deficient mice is rescued by compound loss of the
      noncanonical NF-kappaB p100 gene. Thus, these genetic data clearly demonstrate
      that TRAF3 is a critical negative modulator of the noncanonical NF-kappaB pathway
      and that constitutive activation of the noncanonical NF-kappaB pathway causes the
      lethal phenotype of TRAF3-deficient mice.

PMID- 17015638
TI  - Anticonvulsants for nerve agent-induced seizures: The influence of the
      therapeutic dose of atropine.
AB  - Two guinea pig models were used to study the anticonvulsant potency of diazepam,
      midazolam, and scopolamine against seizures induced by the nerve agents tabun,
      sarin, soman, cyclosarin, O-ethyl S-(2
      (diisopropylamino)ethyl)methylphosphonothioate (VX), and O-isobutyl S-(2
      diethylamino)ethyl)-methyl phosphonothioate (VR). Animals instrumented for
      electroencephalogram recording were pretreated with pyridostigmine bromide (0.026
      mg/kg i.m.) 30 min before challenge with 2 x LD50 (s.c.) of a nerve agent. In
      model A, atropine sulfate (2.0 mg/kg i.m.) and pyridine-2-aldoxime methylchloride
      (2-PAM; 25.0 mg/kg i.m.) were given 1 min after nerve agent challenge, and the
      tested anticonvulsant was given (i.m.) 5 min after seizure onset. In model B, a
      lower dose of atropine sulfate (0.1 mg/kg i.m.) was given along with 2-PAM 1 min
      after nerve agent challenge, and the anticonvulsant was given at seizure onset.
      With the lower dose of atropine, seizure occurrence increased to virtually 100%
      for all agents; the time to seizure onset decreased for sarin, cyclosarin, and
      VX; the signs of nerve agent intoxication were more severe; and coma resulted
      frequently with cyclosarin. The anticonvulsant ED50 doses for scopolamine or
      diazepam were, in general, not different between the two models, whereas the
      anticonvulsant ED50 values of midazolam increased 3- to 17-fold with the lower
      atropine dose. Seizure termination times were not systematically effected by the
      different doses of atropine. The order of anticonvulsant effectiveness within
      each model was scopolamine > or = midazolam > diazepam. The findings indicate
      that the dose of atropine given as antidotal therapy can significantly influence
      measures of nerve agent toxicity and responsiveness to anticonvulsant therapy.

PMID- 17015639
TI  - 4-aminopyridine prevents the conformational changes associated with p/c-type
      inactivation in shaker channels.
AB  - The effect of 4-aminopyridine (4-AP) on Kv channel activation has been
      extensively investigated, but its interaction with inactivation is less well
      understood. Voltage-clamp fluorimetry was used to directly monitor the action of
      4-AP on conformational changes associated with slow inactivation of Shaker
      channels. Tetramethylrhodamine-5-maleimide was used to fluorescently label
      substituted cysteine residues in the S3-S4 linker (A359C) and pore (S424C).
      Activation- and inactivation-induced changes in fluorophore microenvironment
      produced fast and slow phases of fluorescence that were modified by 4-AP. In
      Shaker A359C, 4-AP block reduced the slow-phase contribution from 61 +/- 3 to 28
      +/- 5%, suggesting that binding inhibits the conformational changes associated
      with slow inactivation and increased the fast phase that reports channel
      activation from 39 +/- 3 to 72 +/- 5%. In addition, 4-AP enhanced both fast and
      slow phases of fluorescence return upon repolarization (tau reduced from 87 +/-
      15 to 40 +/- 1 ms and from 739 +/- 83 to 291 +/- 21 ms, respectively), suggesting
      that deactivation and recovery from inactivation were enhanced. In addition, the
      effect of 4-AP on the slow phase of fluorescence was dramatically reduced in
      channels with either reduced (T449V) or permanent P-type (W434F) inactivation.
      Interestingly, the slow phase of fluorescence return of W434F channels was
      enhanced by 4-AP, suggesting that 4-AP prevents the transition to C-type
      inactivation in these channels. These data directly demonstrate that 4-AP
      prevents slow inactivation of Kv channels and that 4-AP can bind to P-type
      inactivated channels and selectively inhibit the onset of C-type inactivation.

PMID- 17015640
TI  - Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces
      inflammation in a rabbit model of atherosclerosis.
AB  - Licofelone, a dual anti-inflammatory drug that inhibits 5-lipoxygenase (LOX) and
      cyclooxygenase (COX) enzymes, may have a better cardiovascular profile that
      cycloxygenase-2 inhibitors due to cycloxygenase-1 blockade-mediated
      antithrombotic effect and a better gastrointestinal tolerability. We examined the
      anti-inflammatory effect of licofelone on atherosclerotic lesions as well as in
      isolated neutrophils from whole blood of rabbits compared with a selective
      inhibitor of COX-2, rofecoxib. We also assessed the antithrombotic effect of
      licofelone in rabbit platelet-rich plasma. For this purpose, 30 rabbits underwent
      injury of femoral arteries, and they were randomized to receive 10 mg/kg/day
      licofelone or 5 mg/kg/day rofecoxib or no treatment during 4 weeks with
      atherogenic diet in all cases. Ten healthy rabbits were used as controls.
      Neutrophils and platelets were isolated from peripheral blood of rabbits for ex
      vivo studies. Licofelone reduced intima/media ratio in injured arteries, the
      macrophages infiltration in the neointimal area, monocyte chemoattractant protein
      1 (MCP-1) gene expression, and the activation of nuclear factor-kappaB in rabbit
      atheroma. Moreover, licofelone inhibited COX-2 and 5-LOX protein expression in
      vascular lesions. Rofecoxib only diminished COX-2 protein expression and MCP-1
      gene expression in vascular atheroma. Prostaglandin E(2) in rabbit plasma was
      attenuated by both drugs. Licofelone almost abolished 5-LOX activity by
      inhibiting leukotriene B4 generation in rabbit neutrophils and prevented platelet
      thromboxane B2 production from whole blood. Licofelone reduces neointimal
      formation and inflammation in an atherosclerotic rabbit model more markedly than
      rofecoxib. This effect, together with the antiplatelet activity of licofelone,
      suggests that this drug may have a favorable cardiovascular profile.

PMID- 17015641
TI  - Fine structure of a fine machine.

PMID- 17015642
TI  - The mannose transporter complex: an open door for the macromolecular invasion of
      bacteria.

PMID- 17015643
TI  - The three-dimensional structure of the flagellar rotor from a clockwise-locked
      mutant of Salmonella enterica serovar Typhimurium.
AB  - Three-dimensional reconstructions from electron cryomicrographs of the rotor of
      the flagellar motor reveal that the symmetry of individual M rings varies from 24
      fold to 26-fold while that of the C rings, containing the two motor/switch
      proteins FliM and FliN, varies from 32-fold to 36-fold, with no apparent
      correlation between the symmetries of the two rings. Results from other studies
      provided evidence that, in addition to the transmembrane protein FliF, at least
      some part of the third motor/switch protein, FliG, contributes to a thickening on
      the face of the M ring, but there was no evidence as to whether or not any
      portion of FliG also contributes to the C ring. Of the four morphological
      features in the cross section of the C ring, the feature closest to the M ring is
      not present with the rotational symmetry of the rest of the C ring, but instead
      it has the symmetry of the M ring. We suggest that this inner feature arises from
      a domain of FliG. We present a hypothetical docking in which the C-terminal motor
      domain of FliG lies in the C ring, where it can interact intimately with FliM.

PMID- 17015644
TI  - Bactericidal activity of both secreted and nonsecreted microcin E492 requires the
      mannose permease.
AB  - Microcin E492 (MccE492) is a bactericidal protein secreted by Klebsiella
      pneumoniae that is active against various species of Enterobacteriaceae.
      Interaction of MccE492 with target cells leads to the depolarization and
      permeabilization of their inner membranes. Several MccE492-specific proteins are
      required for the maturation and secretion of active MccE492. Surprisingly, the
      expression of only MceA, the polypeptide backbone of MccE492, is shown here to be
      toxic by itself. We refer to this phenomenon as endogenous MceA bactericidal
      activity to differentiate it from the action of extracellularly secreted MccE492.
      The toxicity of endogenous MceA is enhanced by an efficient targeting to the
      inner membrane. However, a periplasmic intermediate state is not required for
      MceA toxicity. Indeed, endogenous MceA remains fully active when it is fused to
      thioredoxin-1, a fast-folding protein that promotes retention of the C terminus
      of MceA in the cytoplasm. The C-terminal domain of MccE492 is required only for
      delivery from the extracellular environment to the periplasm, and it is not
      required for inner membrane damage. A common component is absolutely essential
      for the bactericidal activity of both endogenous MceA and extracellular MccE492.
      Indeed, toxicity is strictly dependent on the presence of ManYZ, an inner
      membrane protein complex involved in mannose uptake. Based on these findings, we
      propose a new model for cell entry, inner membrane insertion, and toxic activity
      of MccE492.

PMID- 17015645
TI  - Regulatory loop between redox sensing of the NADH/NAD(+) ratio by Rex (YdiH) and
      oxidation of NADH by NADH dehydrogenase Ndh in Bacillus subtilis.
AB  - NADH dehydrogenase is a key component of the respiratory chain. It catalyzes the
      oxidation of NADH by transferring electrons to ubiquinone and establishes a
      proton motive force across the cell membrane. The yjlD (renamed ndh) gene of
      Bacillus subtilis is predicted to encode an enzyme similar to the NADH
      dehydrogenase II of Escherichia coli, encoded by the ndh gene. We have shown that
      the yjlC-ndh operon is negatively regulated by YdiH (renamed Rex), a homolog of
      Rex in Streptomyces coelicolor, and a redox-sensing transcriptional regulator
      that responds to the NADH/NAD(+) ratio. The ndh gene regulates expression of the
      yjlC-ndh operon, as indicated by the fact that mutation in ndh causes a higher
      NADH/NAD(+) ratio. An in vitro study showed that Rex binds to the downstream
      region of the yjlC-ndh promoter and that NAD(+) enhances the binding of Rex to
      the putative Rex-binding sites in the yjlC-ndh operon as well as in the cydABCD
      operon. These results indicated that Rex and Ndh together form a regulatory loop
      which functions to prevent a large fluctuation in the NADH/NAD(+) ratio in B.
      subtilis.

PMID- 17015646
TI  - Altered Ca(2+) regulation of Yop secretion in Yersinia enterocolitica after DNA
      adenine methyltransferase overproduction is mediated by Clp-dependent degradation
      of LcrG.
AB  - DNA methylation by the DNA adenine methyltransferase (Dam) interferes with the
      coordinated expression of virulence functions in an increasing number of
      pathogens. While analyzing the effect of Dam on the virulence of the human
      pathogen Yersinia enterocolitica, we observed type III secretion of Yop effector
      proteins under nonpermissive conditions. Dam alters the Ca(2+) regulation of Yop
      secretion but does not affect the temperature regulation of Yop/Ysc expression.
      The phenotype is different from that of classical "Ca(2+)-blind" mutants of
      Yersinia, as Dam-overproducing (Dam(OP)) strains still translocate Yops polarly
      into eukaryotic cells. Although transcription of the lcrGV and yopN-tyeA operons
      is slightly upregulated, LcrG is absent from lysates of Dam(OP) bacteria, while
      the amounts of YopN and TyeA are not changed. We present evidence that clpXP
      expression increases after Dam overproduction and that the ClpP protease then
      degrades LcrG, thereby releasing a block in type III secretion. This is the first
      example of posttranslational regulation of type III secretion by the Clp protease
      and adds a new flavor to the complex regulatory mechanisms underlying the
      controlled release of effector proteins from bacterial cells.

PMID- 17015647
TI  - A conserved inverted repeat, the LipR box, mediates transcriptional activation of
      the Streptomyces exfoliatus lipase gene by LipR, a member of the STAND class of P
      loop nucleoside triphosphatases.
AB  - Expression of the Streptomyces exfoliatus lipA gene, which encodes an
      extracellular lipase, depends on LipR, a transcriptional activator that belongs
      to the STAND class of P-loop nucleoside triphosphatases. LipR is closely related
      to activators present in some antibiotic biosynthesis clusters of actinomycetes,
      forming the LipR/TchG family of regulators. In this work we showed that purified
      LipR protein is essential for activation of lipA transcription in vitro and that
      this transcription depends on the presence of a conserved inverted repeat, the
      LipR box, located upstream of the lipA promoter. Mutagenesis of the lipA promoter
      region indicated that most transcription depends on LipR binding to the proximal
      half-site of the LipR box in close proximity to the -35 region of the promoter.
      Our experiments also indicated that LipR establishes contact with the RNA
      polymerase on both sides of the LipR box, since some activation was observed when
      only the distal half-site was present or when the entire LipR box was moved
      further upstream. We also showed that the LipR proteins of S. exfoliatus and
      Streptomyces coelicolor are functionally interchangeable both in vitro and in
      vivo, revealing the functional conservation of the regulatory elements in these
      two species.

PMID- 17015648
TI  - Adaptive gene expression in Bacillus subtilis strains deleted for tetL.
AB  - The growth properties of a new panel of Bacillus subtilis tetL deletion strains
      and of a derivative set of strains in which tetL is restored to the chromosome
      support earlier indications that deletion of tetL results in a range of
      phenotypes that are unrelated to tetracycline resistance. These phenotypes were
      not reversed by restoration of a tetL gene to its native locus and were
      hypothesized to result from secondary mutations that arise when multifunctional
      tetL is deleted. Such genetic changes would temper the alkali sensitivity and
      Na(+) sensitivity that accompany loss of the monovalent cation/proton activity of
      TetL. Microarray comparisons of the transcriptomes of wild-type B. subtilis, a
      tetL deletion strain, and its tetL-restored derivative showed that 37 up
      regulated genes and 13 down-regulated genes in the deletion strain did not change
      back to wild-type expression patterns after tetL was returned to the chromosome.
      Up-regulation of the citM gene, which encodes a divalent metal ion-coupled
      citrate transporter, was shown to account for the Co(2+)-sensitive phenotype of
      tetL mutants. The changes in expression of citM and genes encoding other ion
      coupled solute transporters appear to be adaptive to loss of TetL functions in
      alkali and Na(+) tolerance, because they reduce Na(+)-coupled solute uptake and
      enhance solute uptake that is coupled to H(+) entry.

PMID- 17015649
TI  - Defining the Pseudomonas aeruginosa SOS response and its role in the global
      response to the antibiotic ciprofloxacin.
AB  - Pseudomonas aeruginosa infections can be virtually impossible to eradicate, and
      the evolution of resistance during antibiotic therapy is a significant concern.
      In this study, we use DNA microarrays to characterize the global transcriptional
      response of P. aeruginosa to clinical-like doses of the antibiotic ciprofloxacin
      and also to determine the component that is regulated by LexA cleavage and the
      SOS response. We find that genes involved in virtually every facet of metabolism
      are down-regulated in response to ciprofloxacin. The LexA-controlled SOS regulon
      identified by microarray analysis includes only 15 genes but does include several
      genes that encode proteins involved in recombination and replication, including
      two inducible polymerases known to play a role in mutation and the evolution of
      antibiotic resistance in other organisms. The data suggest that the inhibition of
      LexA cleavage during therapy might help combat this pathogen by decreasing its
      ability to adapt and evolve resistance.

PMID- 17015650
TI  - Physiological analysis of the stringent response elicited in an extreme
      thermophilic bacterium, Thermus thermophilus.
AB  - Guanosine tetraphosphate (ppGpp) is a key mediator of stringent control, an
      adaptive response of bacteria to amino acid starvation, and has thus been termed
      a bacterial alarmone. Previous X-ray crystallographic analysis has provided a
      structural basis for the transcriptional regulation of RNA polymerase activity by
      ppGpp in the thermophilic bacterium Thermus thermophilus. Here we investigated
      the physiological basis of the stringent response by comparing the changes in
      intracellular ppGpp levels and the rate of RNA synthesis in stringent (rel(+);
      wild type) and relaxed (relA and relC; mutant) strains of T. thermophilus. We
      found that in wild-type T. thermophilus, as in other bacteria, serine
      hydroxamate, an amino acid analogue that inhibits tRNA(Ser) aminoacylation,
      elicited a stringent response characterized in part by intracellular accumulation
      of ppGpp and that this response was completely blocked in a relA-null mutant and
      partially blocked in a relC mutant harboring a mutation in the ribosomal protein
      L11. Subsequent in vitro assays using ribosomes isolated from wild-type and relA
      and relC mutant strains confirmed that (p)ppGpp is synthesized by ribosomes and
      that mutation of RelA or L11 blocks that activity. This conclusion was further
      confirmed in vitro by demonstrating that thiostrepton or tetracycline inhibits
      (p)ppGpp synthesis. In an in vitro system, (p)ppGpp acted by inhibiting RNA
      polymerase-catalyzed 23S/5S rRNA gene transcription but at a concentration much
      higher than that of the observed intracellular ppGpp pool size. On the other
      hand, changes in the rRNA gene promoter activity tightly correlated with changes
      in the GTP but not ATP concentration. Also, (p)ppGpp exerted a potent inhibitory
      effect on IMP dehydrogenase activity. The present data thus complement the
      earlier structural analysis by providing physiological evidence that T.
      thermophilus does produce ppGpp in response to amino acid starvation in a
      ribosome-dependent (i.e., RelA-dependent) manner. However, it appears that in T.
      thermophilus, rRNA promoter activity is controlled directly by the GTP pool size,
      which is modulated by ppGpp via inhibition of IMP dehydrogenase activity. Thus,
      unlike the case of Escherichia coli, ppGpp may not inhibit T. thermophilus RNA
      polymerase activity directly in vivo, as recently proposed for Bacillus subtilis
      rRNA transcription (L. Krasny and R. L. Gourse, EMBO J. 23:4473-4483, 2004).

PMID- 17015651
TI  - Molecular and biochemical characterization of alpha-glucosidase and alpha
      mannosidase and their clustered genes from the thermoacidophilic archaeon
      Picrophilus torridus.
AB  - The genes encoding a putative alpha-glucosidase (aglA) and an alpha-mannosidase
      (manA) appear to be physically clustered in the genome of the extreme acidophile
      Picrophilus torridus, a situation not found previously in any other organism
      possessing aglA or manA homologs. While archaeal alpha-glucosidases have been
      described, no alpha-mannosidase enzymes from the archaeal kingdom have been
      reported previously. Transcription start site mapping and Northern blot analysis
      revealed that despite their colinear orientation and the small intergenic space,
      the genes are independently transcribed, both producing leaderless mRNA. aglA and
      manA were cloned and overexpressed in Escherichia coli, and the purified
      recombinant enzymes were characterized with respect to their physicochemical and
      biochemical properties. AglA displayed strict substrate specificity and
      hydrolyzed maltose, as well as longer alpha-1,4-linked maltooligosaccharides.
      ManA, on the other hand, hydrolyzed all possible linkage types of alpha
      glycosidically linked mannose disaccharides and was able to hydrolyze
      alpha3,alpha6-mannopentaose, which represents the core structure of many
      triantennary N-linked carbohydrates in glycoproteins. The probable physiological
      role of the two enzymes in the utilization of exogenous glycoproteins and/or in
      the turnover of the organism's own glycoproteins is discussed.

PMID- 17015652
TI  - FtsZ from divergent foreign bacteria can function for cell division in
      Escherichia coli.
AB  - FtsZs from Mycoplasma pulmonis (MpuFtsZ) and Bacillus subtilis (BsFtsZ) are only
      46% and 53% identical in amino acid sequence to FtsZ from Escherichia coli
      (EcFtsZ). In the present study we show that MpuFtsZ and BsFtsZ can function for
      cell division in E. coli provided we make two modifications. First, we replaced
      their C-terminal tails with that from E. coli, giving the foreign FtsZ the
      binding site for E. coli FtsA and ZipA. Second, we selected for mutations in the
      E. coli genome that facilitated division by the foreign FtsZs. These suppressor
      strains arose at a relatively high frequency of 10(-3) to 10(-5), suggesting that
      they involve loss-of-function mutations in multigene pathways. These pathways may
      be negative regulators of FtsZ or structural pathways that facilitate division by
      slightly defective FtsZ. Related suppressor strains were obtained for EcFtsZ
      containing certain point mutations or insertions of yellow fluorescent protein.
      The ability of highly divergent FtsZs to function for division in E. coli is
      consistent with a two-part mechanism. FtsZ assembles the Z ring, and perhaps
      generates the constriction force, through self interactions; the downstream
      division proteins remodel the peptidoglycan wall by interacting with each other
      and the wall. The C-terminal peptide of FtsZ, which binds FtsA, provides the link
      between FtsZ assembly and peptidoglycan remodeling.

PMID- 17015653
TI  - Regulation of mercury resistance in the crenarchaeote Sulfolobus solfataricus.
AB  - Mercuric ion, Hg(II), inactivates generalized transcription in the crenarchaeote
      Sulfolobus solfataricus. Metal challenge simultaneously derepresses transcription
      of mercuric reductase (merA) by interacting with the archaeal transcription
      factor aMerR. Northern blot and primer extension analyses identified two
      additional Hg(II)-inducible S. solfataricus genes, merH and merI (SSO2690),
      located on either side of merA. Transcription initiating upstream of merH at
      promoter merHp was metal inducible and extended through merA and merI, producing
      a merHAI transcript. Northern analysis of a merRA double mutant produced by
      linear DNA recombination demonstrated merHp promoter activity was dependent on
      aMerR to overcome Hg(II) transcriptional inhibition. Unexpectedly, in a merA
      disruption mutant, the merH transcript was transiently induced after an initial
      period of Hg(II)-mediated transcription inhibition, indicating continued Hg(II)
      detoxification. Metal challenge experiments using mutants created by markerless
      exchange verified the identity of the MerR binding site as an inverted repeat
      (IR) sequence overlapping the transcription factor B binding recognition element
      of merHp. The interaction of recombinant aMerR with merHp DNA, studied using
      electrophoretic mobility shift analysis, demonstrated that complex formation was
      template specific and dependent on the presence of the IR sequence but
      insensitive to Hg(II) addition and site-specific IR mutations that relieved in
      vivo merHp repression. Despite containing a motif resembling a distant ArsR
      homolog, these results indicate aMerR remains continuously DNA bound to protect
      and coordinate Hg(II)-responsive control over merHAI transcription. The new
      genetic methods developed in this work will promote experimental studies on S.
      solfataricus and other Crenarchaeota.

PMID- 17015654
TI  - Identification and sequence of a tet(M) tetracycline resistance determinant
      homologue in clinical isolates of Escherichia coli.
AB  - The presence of the tetracycline resistance determinant tet(M) in human clinical
      isolates of Escherichia coli is described for the first time in this report. The
      homologue was >99% identical to the tet(M) genes reported to occur in
      Lactobacillus plantarum, Neisseria meningitidis, and Streptococcus agalactiae,
      and 3% of the residues in its deduced amino acid sequence diverge from tet(M) of
      Staphylococcus aureus. Sequence analysis of the regions immediately flanking the
      gene revealed that sequences upstream of tet(M) in E. coli have homology to
      Tn916; however, a complete IS26 insertion element was present immediately
      upstream of the promoter element. Downstream from the termination codon is an
      insertion sequence that was homologous to the ISVs1 element reported to occur in
      a plasmid from Vibrio salmonicida that has been associated with another
      tetracycline resistance determinant, tet(E). Results of mating experiments
      demonstrated that the E. coli tet(M) gene was on a mobile element so that
      resistance to tetracycline and minocycline could be transferred to a susceptible
      strain by conjugation. Expression of the cloned tet(M) gene, under the control of
      its own promoter, provided tetracycline and minocycline resistance to the E. coli
      host.

PMID- 17015655
TI  - Time-dependent proteome alterations under osmotic stress during aerobic and
      anaerobic growth in Escherichia coli.
AB  - Escherichia coli lives in the mammalian gastrointestinal tract anaerobically at
      high osmolarity as well as in the soil aerobically at varying osmolarities.
      Adaptation to these varying environmental conditions is crucial for growth and
      survival of E. coli. Two-dimensional protein gels were used to visualize global
      time-dependent changes (10 to 60 min) in the proteome of cells responding to
      osmotic stress (0.4 M NaCl or 0.7 M sorbitol) under aerobic or anaerobic
      conditions. The protein profiles revealed an induction of 12 proteins (Dps, HchA,
      HdhA, InfB, OsmC, OsmY, ProX, KatE, PspA, TalA, TktB, and TreF) under osmotic
      stress in an aerobic milieu. Eleven additional proteins (OtsB, YceI, YciE, YciF,
      YgaU, YjbJ, AcnA, MetL, PoxB, Ssb, and YhbO) were induced by osmotic stress
      imposed by NaCl. Most of the accumulated proteins were cross-protecting proteins
      (e.g., OsmY, OsmC, Dps, and KatE) which are regulated at the transcriptional
      level predominantly by RpoS and other regulators (e.g., integration host factor,
      OxyR, H-NS, LRP, and FIS). Comparative analysis of the proteome of E. coli grown
      under aerobic or anaerobic conditions under osmotic stress (NaCl) revealed an
      overlap of the up-regulated proteins of more than 50%. Ten proteins (PoxB, AcnA,
      TalA, TktB, KatE, PspA, Ssb, TreF, MetL, and YhbO) were detectable only under
      aerobic, high-osmolality conditions. Time-dependent alterations of the proteome
      were monitored, allowing classification of the up-regulated proteins into early,
      middle, and long-term phases of adaptation. Only a few proteins were found to be
      down-regulated upon osmotic stress.

PMID- 17015656
TI  - Positive selection on transposase genes of insertion sequences in the
      Crocosphaera watsonii genome.
AB  - Insertion sequences (ISs) are mobile elements that are commonly found in
      bacterial genomes. Here, the structural and functional diversity of these mobile
      elements in the genome of the cyanobacterium Crocosphaera watsonii WH8501 is
      analyzed. The number, distribution, and diversity of nucleotide and amino acid
      stretches with similarity to the transposase gene of this IS family suggested
      that this genome harbors many functional as well as truncated IS fragments. The
      selection pressure acting on full-length transposase open reading frames of these
      ISs suggested (i) the occurrence of positive selection and (ii) the presence of
      one or more positively selected codons. These results were obtained using three
      data sets of transposase genes from the same IS family that were collected based
      on the level of amino acid similarity, the presence of an inverted repeat, and
      the number of sequences in the data sets. Neither recombination nor ribosomal
      frameshifting, which may interfere with the selection analyses, appeared to be
      important forces in the transposase gene family. Some positively selected codons
      were located in a conserved domain, suggesting that these residues are
      functionally important. The finding that this type of selection acts on IS
      carried genes is intriguing, because although ISs have been associated with the
      adaptation of the bacterial host to new environments, this has typically been
      attributed to transposition or transformation, thus involving different genomic
      locations. Intragenic adaptation of IS-carried genes identified here may
      constitute a novel mechanism associated with bacterial diversification and
      adaptation.

PMID- 17015657
TI  - Differential effects of yfgL mutation on Escherichia coli outer membrane proteins
      and lipopolysaccharide.
AB  - YfgL together with NlpB, YfiO, and YaeT form a protein complex to facilitate the
      insertion of proteins into the outer membrane of Escherichia coli. Without YfgL,
      the levels of OmpA, OmpF, and LamB are significantly reduced, while OmpC levels
      are slightly reduced. In contrast, the level of TolC significantly increases in a
      yfgL mutant. When cells are depleted of YaeT or YfiO, levels of all outer
      membrane proteins examined, including OmpC and TolC, are severely reduced. Thus,
      while the assembly pathways of various nonlipoprotein outer membrane proteins may
      vary through the step involving YfgL, all assembly pathways in Escherichia coli
      converge at the step involving the YaeT/YfiO complex. The negative effect of yfgL
      mutation on outer membrane proteins may in part be due to elevated sigma E
      activity, which has been shown to downregulate the synthesis of various outer
      membrane proteins while upregulating the synthesis of periplasmic chaperones,
      foldases, and lipopolysaccharide. The data presented here suggest that the yfgL
      effect on outer membrane proteins also stems from a defective assembly apparatus,
      leading to aberrant outer membrane protein assembly, except for TolC, which
      assembles independent of YfgL. Consistent with this view, the simultaneous
      absence of YfgL and the major periplasmic protease DegP confers a synthetic
      lethal phenotype, presumably due to the toxic accumulation of unfolded outer
      membrane proteins. The results support the hypothesis that TolC and major outer
      membrane proteins compete for the YaeT/YfiO complex, since mutations that
      adversely affect synthesis or assembly of major outer membrane proteins lead to
      elevated TolC levels.

PMID- 17015658
TI  - Interrelations between glycine betaine catabolism and methionine biosynthesis in
      Sinorhizobium meliloti strain 102F34.
AB  - Methionine is produced by methylation of homocysteine. Sinorhizobium meliloti
      102F34 possesses only one methionine synthase, which catalyzes the transfer of a
      methyl group from methyl tetrahydrofolate to homocysteine. This vitamin B(12)
      dependent enzyme is encoded by the metH gene. Glycine betaine can also serve as
      an alternative methyl donor for homocysteine. This reaction is catalyzed by
      betaine-homocysteine methyl transferase (BHMT), an enzyme that has been
      characterized in humans and rats. An S. meliloti gene whose product is related to
      the human BHMT enzyme has been identified and named bmt. This enzyme is closely
      related to mammalian BHMTs but has no homology with previously described
      bacterial betaine methyl transferases. Glycine betaine inhibits the growth of an
      S. meliloti bmt mutant in low- and high-osmotic strength media, an effect that
      correlates with a decrease in the catabolism of glycine betaine. This inhibition
      was not observed with other betaines, like homobetaine,
      dimethylsulfoniopropionate, and trigonelline. The addition of methionine to the
      growth medium allowed a bmt mutant to recover growth despite the presence of
      glycine betaine. Methionine also stimulated glycine betaine catabolism in a bmt
      strain, suggesting the existence of another catabolic pathway. Inactivation of
      metH or bmt did not affect the nodulation efficiency of the mutants in the 102F34
      strain background. Nevertheless, a metH strain was severely defective in
      competing with the wild-type strain in a coinoculation experiment.

PMID- 17015659
TI  - Heterologous expression, purification, and characterization of an l-ornithine
      N(5)-hydroxylase involved in pyoverdine siderophore biosynthesis in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that produces the siderophore
      pyoverdine, which enables it to acquire the essential nutrient iron from its
      host. Formation of the iron-chelating hydroxamate functional group in pyoverdine
      requires the enzyme PvdA, a flavin-dependent monooxygenase that catalyzes the
      N(5) hydroxylation of l-ornithine. pvdA from P. aeruginosa was successfully
      overexpressed in Escherichia coli, and the enzyme was purified for the first
      time. The enzyme possessed its maximum activity at pH 8.0. In the absence of l
      ornithine, PvdA has an NADPH oxidase activity of 0.24 +/- 0.02 micromol min(-1)
      mg(-1). The substrate l-ornithine stimulated this activity by a factor of 5, and
      the reaction was tightly coupled to the formation of hydroxylamine. The enzyme is
      specific for NADPH and flavin adenine dinucleotide (FAD(+)) as cofactors, as it
      cannot utilize NADH and flavin mononucleotide. By fluorescence titration, the
      dissociation constants for NADPH and FAD(+) were determined to be 105.6 +/- 6.0
      microM and 9.9 +/- 0.3 microM, respectively. Steady-state kinetic analysis showed
      that the l-ornithine-dependent NADPH oxidation obeyed Michaelis-Menten kinetics
      with apparent K(m) and V(max) values of 0.58 mM and 1.34 micromol min(-1) mg(-1).
      l-Lysine was a nonsubstrate effector that stimulated NADPH oxidation, but
      uncoupling occurred and hydrogen peroxide instead of hydroxylated l-lysine was
      produced. l-2,4-Diaminobutyrate, l-homoserine, and 5-aminopentanoic acid were not
      substrates or effectors, but they were competitive inhibitors of the l-ornithine
      dependent NADPH oxidation reaction, with K(ic)s of 3 to 8 mM. The results
      indicate that the chemical nature of effectors is important for simulation of the
      NADPH oxidation rate in PvdA.

PMID- 17015660
TI  - AmiC functions as an N-acetylmuramyl-l-alanine amidase necessary for cell
      separation and can promote autolysis in Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is prone to undergo autolysis under many conditions not
      conducive to growth. The role of autolysis during gonococcal infection is not
      known, but possible advantages for the bacterial population include provision of
      nutrients to a starving population, modulation of the host immune response by
      released cell components, and donation of DNA for natural transformation.
      Biochemical studies indicated that an N-acetylmuramyl-l-alanine amidase is
      responsible for cell wall breakdown during autolysis. In order to better
      understand autolysis and in hopes of creating a nonautolytic mutant, we mutated
      amiC, the gene for a putative peptidoglycan-degrading amidase in N. gonorrhoeae.
      Characterization of peptidoglycan fragments released during growth showed that an
      amiC mutant did not produce free disaccharide, consistent with a role for AmiC as
      an N-acetylmuramyl-l-alanine amidase. Compared to the wild-type parent, the
      mutant exhibited altered growth characteristics, including slowed exponential
      phase growth, increased turbidity in stationary phase, and increased colony
      opacity. Thin-section electron micrographs showed that mutant cells did not fully
      separate but grew as clumps. Complementation of the amiC deletion mutant with
      wild-type amiC restored wild-type growth characteristics and transparent colony
      morphology. Overexpression of amiC resulted in increased cell lysis, supporting
      AmiC's purported function as a gonococcal autolysin. However, amiC mutants still
      underwent autolysis in stationary phase, indicating that other gonococcal enzymes
      are also involved in this process.

PMID- 17015661
TI  - The sigma(E) cell envelope stress response of Streptomyces coelicolor is
      influenced by a novel lipoprotein, CseA.
AB  - We have investigated the role of CseA in the sigma(E) cell envelope stress
      response of the gram-positive bacterium Streptomyces coelicolor. sigma(E) is an
      extracytoplasmic function RNA polymerase sigma factor required for normal cell
      envelope integrity in S. coelicolor. sigma(E) is encoded within a four-gene
      operon that also encodes CseA, a protein of unknown function, CseB, a response
      regulator and CseC, a transmembrane sensor histidine kinase (Cse represents
      control of sigma E). Previous work has shown that transcription of the sigE gene
      is completely dependent on the CseBC two-component system and that the CseBC
      sigma(E) signal transduction system is induced by a wide variety of cell-wall
      damaging agents. Here we address the role of CseA, a protein with no homologues
      outside the streptomycetes. We show that CseA is a novel lipoprotein localized to
      the extracytoplasmic face of the cell membrane and that loss of CseA results in
      upregulation of the sigE promoter.

PMID- 17015662
TI  - The Rgg regulator of Streptococcus pyogenes influences utilization of nonglucose
      carbohydrates, prophage induction, and expression of the NAD-glycohydrolase
      virulence operon.
AB  - The expression of many virulence-associated genes in Streptococcus pyogenes is
      controlled in a growth phase-dependent manner. Unlike the model organisms
      Escherichia coli and Bacillus subtilis, such regulation is apparently not
      dependent upon alternative sigma factors but appears to rely on complex
      interactions among several transcriptional regulators, including Rgg. The purpose
      of this study was to identify changes in gene expression associated with
      inactivation of the rgg gene in S. pyogenes strain NZ131 (serotype M49). To this
      end, the transcriptomes of wild-type and rgg mutant strains were analyzed during
      both the exponential and postexponential phases of growth using Affymetrix
      NimbleExpress gene chips. Genomewide differences in transcript levels were
      identified in both phases of growth. Inactivation of rgg disrupted coordinate
      expression of genes associated with the metabolism of nonglucose carbon sources,
      such as fructose, mannose, and sucrose. The changes were associated with an
      inability of the mutant strain to grow using these compounds as the primary
      carbon source. Bacteriophage transcript levels were also altered in the mutant
      strain and were associated with decreased induction of at least one prophage.
      Finally, transcripts encoding virulence factors involved in cytolysin-mediated
      translocation of NAD-glycohydrolase, including the immunity factor IFS and the
      cytolysin (streptolysin O [SLO]), were more abundant in the mutant strain, which
      correlated with the amount of NADase and SLO activities in culture supernatant
      fluids. The results provide further evidence that Rgg contributes to growth phase
      dependent gene regulation in strain NZ131.

PMID- 17015663
TI  - Survival and growth in the presence of elevated copper: transcriptional profiling
      of copper-stressed Pseudomonas aeruginosa.
AB  - Transcriptional profiles of Pseudomonas aeruginosa exposed to two separate copper
      stress conditions were determined. Actively growing bacteria subjected to a pulse
      of elevated copper for a short period of time was defined as a "copper-shocked"
      culture. Conversely, copper-adapted populations were defined as cells actively
      growing in the presence of elevated copper. Expression of 405 genes changed in
      the copper-shocked culture, compared to 331 genes for the copper-adapted
      cultures. Not surprisingly, there were genes identified in common to both
      conditions. For example, both stress conditions resulted in up-regulation of
      genes encoding several active transport functions. However, there were some
      interesting differences between the two types of stress. Only copper-adapted
      cells significantly altered expression of passive transport functions, down
      regulating expression of several porins belonging to the OprD family. Copper
      shock produced expression profiles suggestive of an oxidative stress response,
      probably due to the participation of copper in Fenton-like chemistry. Copper
      adapted populations did not show such a response. Transcriptional profiles also
      indicated that iron acquisition is fine-tuned in the presence of copper. Several
      genes induced under iron-limiting conditions, such as the siderophore pyoverdine,
      were up-regulated in copper-adapted populations. Interesting exceptions were the
      genes involved in the production of the siderophore pyochelin, which were down
      regulated. Analysis of the copper sensitivity of select mutant strains confirmed
      the array data. These studies suggest that two resistance nodulation division
      efflux systems, a P-type ATPase, and a two-component regulator were particularly
      important for copper tolerance in P. aeruginosa.

PMID- 17015664
TI  - The genome sequence of Mannheimia haemolytica A1: insights into virulence,
      natural competence, and Pasteurellaceae phylogeny.
AB  - The draft genome sequence of Mannheimia haemolytica A1, the causative agent of
      bovine respiratory disease complex (BRDC), is presented. Strain ATCC BAA-410,
      isolated from the lung of a calf with BRDC, was the DNA source. The annotated
      genome includes 2,839 coding sequences, 1,966 of which were assigned a function
      and 436 of which are unique to M. haemolytica. Through genome annotation many
      features of interest were identified, including bacteriophages and genes related
      to virulence, natural competence, and transcriptional regulation. In addition to
      previously described virulence factors, M. haemolytica encodes adhesins,
      including the filamentous hemagglutinin FhaB and two trimeric autotransporter
      adhesins. Two dual-function immunoglobulin-protease/adhesins are also present, as
      is a third immunoglobulin protease. Genes related to iron acquisition and drug
      resistance were identified and are likely important for survival in the host and
      virulence. Analysis of the genome indicates that M. haemolytica is naturally
      competent, as genes for natural competence and DNA uptake signal sequences (USS)
      are present. Comparison of competence loci and USS in other species in the family
      Pasteurellaceae indicates that M. haemolytica, Actinobacillus pleuropneumoniae,
      and Haemophilus ducreyi form a lineage distinct from other Pasteurellaceae. This
      observation was supported by a phylogenetic analysis using sequences of predicted
      housekeeping genes.

PMID- 17015665
TI  - Blocking chromosome translocation during sporulation of Bacillus subtilis can
      result in prespore-specific activation of sigmaG that is independent of sigmaE
      and of engulfment.
AB  - Formation of spores by Bacillus subtilis is characterized by cell compartment
      specific gene expression directed by four RNA polymerase sigma factors, which are
      activated in the order sigma(F)-sigma(E)-sigma(G)-sigma(K). Of these, sigma(G)
      becomes active in the prespore upon completion of engulfment of the prespore by
      the mother cell. Transcription of the gene encoding sigma(G), spoIIIG, is
      directed in the prespore by RNA polymerase containing sigma(F) but also requires
      the activity of sigma(E) in the mother cell. When first formed, sigma(G) is not
      active. Its activation requires expression of additional sigma(E)-directed genes,
      including the genes required for completion of engulfment. Here we report
      conditions in which sigma(G) becomes active in the prespore in the absence of
      sigma(E) activity and of completion of engulfment. The conditions are (i) having
      an spoIIIE mutation, so that only the origin-proximal 30% of the chromosome is
      translocated into the prespore, and (ii) placing spoIIIG in an origin-proximal
      location on the chromosome. The main function of the sigma(E)-directed regulation
      appears to be to coordinate sigma(G) activation with the completion of
      engulfment, not to control the level of sigma(G) activity. It seems plausible
      that the role of sigma(E) in sigma(G) activation is to reverse some inhibitory
      signal (or signals) in the engulfed prespore, a signal that is not present in the
      spoIIIE mutant background. It is not clear what the direct activator of sigma(G)
      in the prespore is. Competition for core RNA polymerase between sigma(F) and
      sigma(G) is unlikely to be of major importance.

PMID- 17015666
TI  - Differential regulation of the three methanol methyltransferase isozymes in
      Methanosarcina acetivorans C2A.
AB  - Genetic analysis of the three methanol-specific methyltransferase 1 operons
      (mtaCB1, mtaCB2, and mtaCB3) in Methanosarcina acetivorans led to the suggestion
      that each of them has a discrete function during growth on methanol, which might
      be reflected in differential gene regulation (Pritchett and Metcalf, Mol.
      Microbiol. 56:1183-1194, 2005). To test this suggestion, reporter gene fusions
      were constructed for each of the three operons, and their expression was examined
      under various growth conditions. Expression of the mtaCB1 and mtaCB2 fusions was
      100-fold and 575-fold higher, respectively, in methanol-grown cells than in
      trimethylamine (TMA)-grown cells. The mtaCB3 fusion was expressed at low levels
      on methanol, TMA, and dimethylamine but was significantly upregulated on
      monomethylamine and acetate. When TMA- or acetate-grown cultures were shifted to
      methanol, the mtaCB1 fusion was expressed most highly during exponential phase,
      whereas the mtaCB2 fusion, although strongly induced prior to mtaCB1 expression,
      did not reach full expression levels until stationary phase. The mtaCB3 fusion
      was transiently expressed prior to entry into exponential phase during a TMA-to
      methanol substrate shift experiment. When acetate-grown cells were shifted to
      medium containing both TMA and methanol, TMA utilization commenced prior to
      utilization of methanol; however, these two substrates were consumed
      simultaneously later in growth. Under these conditions expression of the mtaCB2
      and mtaCB3 fusions was delayed, suggesting that methylamines may repress their
      expression.

PMID- 17015667
TI  - Threonine-978 in the transmembrane segment of the multidrug efflux pump AcrB of
      Escherichia coli is crucial for drug transport as a probable component of the
      proton relay network.
AB  - Escherichia coli AcrB is a multidrug efflux transporter that recognizes multiple
      toxic chemicals and expels them from cells. It is a proton antiporter belonging
      to the resistance-nodulation-division (RND) superfamily. Asp407, Asp408, Lys940,
      and Arg971 in transmembrane (TM) helices of this transporter have been identified
      as essential amino acid residues that probably function as components of the
      proton relay system. In this study, we identified a novel residue in TM helix 11,
      Thr978, as an essential residue by alanine scanning mutagenesis. Its location
      close to Asp407 suggests that it is also a component of the proton translocation
      pathway, a prediction confirmed by the similar conformations adopted by T978A,
      D407A, D408A, and K940A mutant proteins (see the accompanying paper). Sequence
      alignment of 566 RND transporters showed that this threonine residue is conserved
      in about 96% of cases. Our results suggest the hypotheses that Thr978 functions
      through hydrogen bonding with Asp407 and that protonation of the latter alters
      the salt bridging and hydrogen bonding pattern in the proton relay network, thus
      initiating a series of conformational changes that ultimately result in drug
      extrusion.

PMID- 17015668
TI  - Conformation of the AcrB multidrug efflux pump in mutants of the putative proton
      relay pathway.
AB  - We previously reported the X-ray structures of wild-type Escherichia coli AcrB, a
      proton motive force-dependent multidrug efflux pump, and its N109A mutant. These
      structures presumably reflect the resting state of AcrB, which can bind drugs.
      After ligand binding, a proton may bind to an acidic residue(s) in the
      transmembrane domain, i.e., Asp407 or Asp408, within the putative network of
      electrostatically interacting residues, which also include Lys940 and Thr978, and
      this may initiate a series of conformational changes that result in drug
      expulsion. Herein we report the X-ray structures of four AcrB mutants, the D407A,
      D408A, K940A, and T978A mutants, in which the structure of this tight
      electrostatic network is expected to become disrupted. These mutant proteins
      revealed remarkably similar conformations, which show striking differences from
      the previously known conformations of the wild-type protein. For example, the
      loop containing Phe386 and Phe388, which play a major role in the initial binding
      of substrates in the central cavity, becomes prominently extended into the center
      of the cavity, such that binding of large substrate molecules may become
      difficult. We believe that this new conformation may mimic, at least partially,
      one of the transient conformations of the transporter during the transport cycle.

PMID- 17015669
TI  - Comparative phylogenomics of Clostridium difficile reveals clade specificity and
      microevolution of hypervirulent strains.
AB  - Clostridium difficile is the most frequent cause of nosocomial diarrhea
      worldwide, and recent reports suggested the emergence of a hypervirulent strain
      in North America and Europe. In this study, we applied comparative phylogenomics
      (whole-genome comparisons using DNA microarrays combined with Bayesian
      phylogenies) to model the phylogeny of C. difficile, including 75 diverse
      isolates comprising hypervirulent, toxin-variable, and animal strains. The
      analysis identified four distinct statistically supported clusters comprising a
      hypervirulent clade, a toxin A(-) B(+) clade, and two clades with human and
      animal isolates. Genetic differences among clades revealed several genetic
      islands relating to virulence and niche adaptation, including antibiotic
      resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were
      shared by all strains, confirming that this enteric species readily undergoes
      genetic exchange. This study has provided insight into the possible origins of C.
      difficile and its evolution that may have implications in disease control
      strategies.

PMID- 17015670
TI  - Phototaxis and impaired motility in adenylyl cyclase and cyclase receptor protein
      mutants of Synechocystis sp. strain PCC 6803.
AB  - We have carefully characterized and reexamined the motility and phototactic
      responses of Synechocystis sp. adenylyl cyclase (Cya1) and catabolite activator
      protein (SYCRP1) mutants to different light regimens, glucose, 3-(3,4
      dichlorophenyl)-1,1-dimethylurea, and cyclic AMP. We find that contrary to
      earlier reports, cya1 and sycrp1 mutants are motile and phototactic but are
      impaired in one particular phase of phototaxis in comparison with wild-type
      Synechocystis sp.

PMID- 17015671
TI  - Replisome localization in vegetative and aerial hyphae of Streptomyces
      coelicolor.
AB  - Using a functional fusion of DnaN to enhanced green fluorescent protein, we
      examined the subcellular localization of the replisome machinery in the
      vegetative mycelium and aerial mycelium of the multinucleoid organism
      Streptomyces coelicolor. Chromosome replication took place in many compartments
      of both types of hypha, with the apical compartments of the aerial mycelium
      exhibiting the highest replication activity. Within a single compartment, the
      number of "current" ongoing DNA replications was lower than the expected
      chromosome number, and the appearance of fluorescent foci was often
      heterogeneous, indicating that this process is asynchronous within compartments
      and that only selected chromosomes undergo replication.

PMID- 17015672
TI  - Evidence for conformational changes within DsbD: possible role for membrane
      embedded proline residues.
AB  - The mechanism by which DsbD transports electrons across the cytoplasmic membrane
      is unknown. Here we provide evidence that DsbD's conformation depends on its
      oxidation state. Our data also suggest that four highly conserved prolines
      surrounding DsbD's membrane-embedded catalytic cysteines may have an important
      functional role, possibly conferring conformational flexibility to DsbD.

PMID- 17015673
TI  - A plasmid-borne truncated luxI homolog controls quorum-sensing systems and
      extracellular carbohydrate production in Methylobacterium extorquens AM1.
AB  - A cryptic plasmid of Methylobacterium extorquens AM1 was found to encode tslI, a
      truncated luxI homolog. tslI was shown to be expressed and to control
      transcription of the acyl-homoserine lactone (HSL) synthase gene msaI and thus,
      indirectly, acyl-HSL production. In addition, tslI was found to positively
      regulate extracellular polysaccharide production.

PMID- 17015674
TI  - Autophagy: eating for good health.
AB  - A renaissance in the autophagy field has illuminated many areas of biology, and
      infectious disease is no exception. By identifying key components of this broadly
      conserved membrane traffic pathway, yeast geneticists generated tools for
      microbiologists and immunologists to explore whether autophagy contributes to
      host defenses. As a result, autophagy is now recognized to be another barrier
      confronted by microbes that invade eukaryotic cells. Mounting evidence also
      indicates that autophagy equips cells to deliver cytosolic Ags to the MHC class
      II pathway. By applying knowledge of the autophagy machinery and exploiting
      microbes as genetic probes, experimentalists can now examine in detail how this
      ancient membrane traffic pathway contributes to these and other mechanisms
      critical for infection and immunity.

PMID- 17015675
TI  - Cutting edge: treatment of complement regulatory protein deficiency by retroviral
      in vivo gene therapy.
AB  - Gene therapy is an attractive means to replace a deficient or defective protein.
      Using a murine retroviral vector, we provide an example of reconstituting a C
      regulator by neonatal in vivo gene transfer. The fusion gene containing the mouse
      C receptor 1-related gene/protein y (Crry) and a single chain Ab fragment with
      specificity for mouse glycophorin A was placed under transcriptional control of a
      liver-specific promoter. Shortly after birth, Crry KO mice were injected with the
      retroviral vectors. Protein expression progressively increased over the next 6-8
      wk after which an equilibrium was established. Coating levels on RBCs were
      obtained that inhibited C activation similar to wild-type cells and remained
      constant for > 1 year. Thus, gene therapy with targeted regulators represents a
      treatment option to provide a long-term and sustained protein supply for the site
      specific blockade of undesirable complement activation.

PMID- 17015676
TI  - Cutting edge: abortive proliferation of CD46-induced Tr1-like cells due to a
      defective Akt/Survivin signaling pathway.
AB  - T regulatory cell 1 (Tr1) are low proliferating peripherally induced suppressive
      T cells. Engaging CD3 and CD46 on human CD4+ T cells induces a Tr1-like
      phenotype. In this study, we report that human Tr1-like cells do not sustain
      proliferation over time. The weak proliferation of these cells results first from
      their inability to sustain expression of various cell cycle-associated proteins,
      to efficiently degrade the inhibitor of cell cycle progression p27/Kip1 and, as a
      consequence, in their accumulation in the G0-G1 phase. Also, the reduced
      proliferation of Tr1-like cells results from their increased sensitivity to death
      as they divide, through a mechanism that is neither Fas-mediated nor Bcl2/Bcl-xL
      related. Both properties, impaired cell cycle and death sensitivity, are
      explained by a specific defective activation of Akt that impairs the expression
      of Survivin. Thus, our results show that CD3/CD46-induced Tr1-like cells die
      through a process of abortive proliferation.

PMID- 17015677
TI  - Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short
      isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes.
AB  - To evaluate the role of hypoxia-inducible factor 1alpha (HIF-1alpha) and its TCR
      activation-inducible short isoform I.1 in T cell functions, we genetically
      engineered unique mice with: 1) knockout of I.1 isoform of HIF-1alpha; 2) T cell
      targeted HIF-1alpha knockdown; and 3) chimeric mice with HIF-1alpha gene deletion
      in T and B lymphocytes. In all three types of mice, the HIF-1alpha-deficient T
      lymphocytes, which were TCR-activated in vitro, produced more proinflammatory
      cytokines compared with HIF-1alpha-expressing control T cells. Surprisingly,
      deletion of the I.1 isoform, which represents < 30% of total HIF-1alpha mRNA in
      activated T cells, was sufficient to markedly enhance TCR-triggered cytokine
      secretion. These data suggest that HIF-1alpha not only plays a critical role in
      oxygen homeostasis but also may serve as a negative regulator of T cells.

PMID- 17015678
TI  - Cutting edge: inhibition of T cell activation by TIM-2.
AB  - T cell Ig and mucin domain protein 2 (TIM-2) has been shown to regulate T cell
      activation in vitro and T cell-mediated disease in vivo. However, it is still not
      clear whether TIM-2 acts mainly to augment T cell function or to inhibit it. We
      have directly examined the function of TIM-2 in murine and human T cell lines.
      Our results indicate that expression of TIM-2 significantly impairs the induction
      of NFAT and AP-1 transcriptional reporters by not only TCR ligation but also by
      the pharmacological stimuli PMA and ionomycin. This does not appear to be due to
      a general effect on cell viability, and the block in NFAT activation can be
      bypassed by expression of activated alleles of Ras or calcineurin, or MEK kinase,
      in the case of AP-1. Thus, our data are consistent with a model whereby TIM-2
      inhibits T cell activation.

PMID- 17015679
TI  - Effect of lipid rafts on Cb2 receptor signaling and 2-arachidonoyl-glycerol
      metabolism in human immune cells.
AB  - Recently, we have shown that treatment of rat C6 glioma cells with the raft
      disruptor methyl-beta-cyclodextrin (MCD) doubles the binding of anandamide (AEA)
      to type-1 cannabinoid receptors (CB1R), followed by CB1R-dependent signaling via
      adenylate cyclase and p42/p44 MAPK activity. In the present study, we
      investigated whether type-2 cannabinoid receptors (CB2R), widely expressed in
      immune cells, also are modulated by MCD. We show that treatment of human DAUDI
      leukemia cells with MCD does not affect AEA binding to CB2R, and that receptor
      activation triggers similar [35S]guanosine-5'-O-(3-thiotriphosphate) binding in
      MCD-treated and control cells, similar adenylate cyclase and MAPK activity, and
      similar MAPK-dependent protection against apoptosis. The other AEA-binding
      receptor transient receptor potential channel vanilloid receptor subunit 1, the
      AEA synthetase N-acyl-phosphatidylethanolamine-phospholipase D, and the AEA
      hydrolase fatty acid amide hydrolase were not affected by MCD, whereas the AEA
      membrane transporter was inhibited (approximately 55%) compared with controls.
      Furthermore, neither diacylglycerol lipase nor monoacylglycerol lipase, which
      respectively synthesize and degrade 2-arachidonoylglycerol, were affected by MCD
      in DAUDI or C6 cells, whereas the transport of 2-arachidonoylglycerol was reduced
      to approximately 50%. Instead, membrane cholesterol enrichment almost doubled the
      uptake of AEA and 2-arachidonoylglycerol in both cell types. Finally,
      transfection experiments with human U937 immune cells, and the use of primary
      cells expressing CB1R or CB2R, ruled out that the cellular environment could
      account per se for the different modulation of CB receptor subtypes by MCD. In
      conclusion, the present data demonstrate that lipid rafts control CB1R, but not
      CB2R, and endocannabinoid transport in immune and neuronal cells.

PMID- 17015680
TI  - DAP12 signaling directly augments proproliferative cytokine stimulation of NK
      cells during viral infections.
AB  - NK cells vigorously proliferate during viral infections. During the course of
      murine CMV infection, this response becomes dominated by the preferential
      proliferation of NK cells that express the activation receptor Ly49H. The factors
      driving such selective NK cell proliferation have not been characterized. In this
      study, we demonstrate that preferential NK cell proliferation is dependent on
      DAP12-mediated signaling following the binding of Ly49H to its virally encoded
      ligand, m157. Ly49H signaling through DAP12 appears to directly augment NK cell
      sensitivity to low concentrations of proproliferative cytokines such as IL-15.
      The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the
      presence of high concentrations of proproliferative cytokines that nonselectively
      drive all NK cells to proliferate.

PMID- 17015681
TI  - Role of galectin-3 in mast cell functions: galectin-3-deficient mast cells
      exhibit impaired mediator release and defective JNK expression.
AB  - Galectin-3 is a member of the beta-galactoside-binding animal lectin family
      expressed in various cell types, including mast cells. To determine the role of
      galectin-3 in the function of mast cells, we studied bone marrow-derived mast
      cells (BMMC) from wild-type (gal3(+/+)) and galectin-3-deficient (gal3(-/-))
      mice. Cells from the two genotypes showed comparable expression of IgE receptor
      and c-Kit. However, upon activation by FcepsilonRI cross-linkage, gal3(-/-) BMMC
      secreted a significantly lower amount of histamine as well as the cytokine IL-4,
      compared with gal3(+/+) BMMC. In addition, we found significantly reduced passive
      cutaneous anaphylaxis reactions in gal3(-/-) mice compared with gal3(+/+) mice.
      These results indicate that there is a defect in the response of mast cells in
      gal3(-/-) mice. Unexpectedly, we found that gal3(-/-) BMMC contained a
      dramatically lower basal level of JNK1 protein compared with gal3(+/+) BMMC,
      which is probably responsible for the lower IL-4 production. The decreased JNK1
      level in gal3(-/-) BMMC is accompanied by a lower JNK1 mRNA level, suggesting
      that galectin-3 regulates the transcription of the JNK gene or processing of its
      RNA. All together, these results point to an important role of galectin-3 in mast
      cell biology.

PMID- 17015682
TI  - Differential usage of cellular niches by cytomegalovirus versus EBV- and
      influenza virus-specific CD8+ T cells.
AB  - Immunological memory provides long-term protection against reinfection or
      reactivation of pathogens. Murine memory T cell populations may be compressed
      following infections with new pathogens. Humans have to retain memory T cells
      directed against a variety of microbes for many decades. Under these
      circumstances, the effect of pathogens that mount robust T cell reactivity on the
      pre-existing memory directed against unrelated microbes is unknown. In this
      study, we studied peripheral blood memory CD8+ T cells directed against different
      viruses following primary CMV infection in renal transplant recipients. The
      entrance of CMV-specific CD8+ T cells expanded the Ag-primed CD8+ T cell
      compartment rather than competing for space with pre-existing memory T cells
      specific for persistent or cleared viruses. Neither numbers nor phenotype of EBV-
      or influenza-specific CD8+ T cells was altered by primary CMV infection. CMV
      specific CD8+ T cells accumulated over time, resulting in increased total CD8+ T
      cell numbers. Additionally, they acquired a highly differentiated cytolytic
      phenotype that was clearly distinct from EBV- or influenza-reactive T cells.
      Thus, the human immune system appears to be flexible and is able to expand when
      encountering CMV. In view of the phenotypic differences between virus-specific T
      cells, this expansion may take place in cellular niches different from those
      occupied by EBV- or influenza-specific T cells, thereby preserving immunity to
      these pathogens.

PMID- 17015683
TI  - IFN-gamma-mediated inhibition of human IgE synthesis by IL-21 is associated with
      a polymorphism in the IL-21R gene.
AB  - IL-21 is a cytokine produced by CD4+ T cells that has been reported to regulate
      human, as well as, mouse T and NK cell function and to inhibit Ag-induced IgE
      production by mouse B cells. In the present study, we show that human rIL-21
      strongly enhances IgE production by both CD19+ CD27- naive, and CD19+ CD27+
      memory B cells, stimulated with anti-CD40 mAb and rIL-4 and that it promotes the
      proliferative responses of these cells. However, rIL-21 does not significantly
      affect anti-CD40 mAb and rIL-4-induced Cepsilon promoter activation in a gene
      reporter assay, nor germline Cepsilon mRNA expression in purified human spleen or
      peripheral blood B cells. In contrast, rIL-21 inhibits rIL-4-induced IgE
      production in cultures of PBMC or total splenocytes by an IFN-gamma-dependent
      mechanism. The presence of a polymorphism (T-83C), in donors heterozygous for
      this mutation was found to be associated not only with lower rIL-21-induced IFN
      gamma production levels, but also with a lower sensitivity to the inhibitory
      effects of IL-21 on the production of IgE, compared with those in donors
      expressing the wild-type IL-21R. Taken together, these results show that IL-21
      differentially regulates IL-4-induced human IgE production, via its growth- and
      differentiation-promoting capacities on isotype-, including IgE-, committed B
      cells, as well as via its ability to induce IFN-gamma production, most likely by
      T and NK cells, whereas the outcome of these IL-21-mediated effects is dependent
      on the presence of a polymorphism in the IL-21R.

PMID- 17015684
TI  - Peripheral T cell lymphopenia and concomitant enrichment in naturally arising
      regulatory T cells: the case of the pre-Talpha gene-deleted mouse.
AB  - In pre-Talpha (pTalpha) gene-deleted mice, the positively selectable CD4+ CD8+
      double-positive thymocyte pool is only 1% that in wild-type mice. Consequently,
      their peripheral T cell compartment is severely lymphopenic with a concomitant
      increase in proportion of CD25+ FoxP3+ regulatory T cells. Using mixed bone
      marrow chimeras, where thymic output was 1% normal, the pTalpha(-/-) peripheral T
      cell phenotype could be reproduced with normal cells. In the pTalpha(-/-) thymus
      and peripheral lymphoid organs, FoxP3+ CD4+ cells were enriched. Parabiosis
      experiments showed that many pTalpha(-/-) CD4+ single-positive thymocytes
      represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+
      CD4+ single-positive thymocytes was not solely due to increased thymic
      production. Thus, the pTalpha(-/-) mouse serves as a model system with which to
      study the consequences of chronic decreased thymic T cell production on the
      physiology of the peripheral T cell compartment.

PMID- 17015685
TI  - Vav1 promotes T cell cycle progression by linking TCR/CD28 costimulation to FOXO1
      and p27kip1 expression.
AB  - Vav proteins play a critical role in T cell activation and proliferation by
      promoting cytoskeleton reorganization, transcription factor activation, and
      cytokine production. In this study, we investigated the role of Vav in T cell
      cycle progression. TCR/CD28-stimulated Vav1(-/-) T cells displayed a cell cycle
      block at the G0-G1 stage, which accounted for their defective proliferation. This
      defect was associated with impaired TCR/CD28-induced phosphorylation of Akt and
      the Forkhead family transcription factor, FOXO1. The cytoplasmic localization of
      FOXO1 and its association with 14-3-3tau were also reduced in Vav1(-/-) T cells.
      Consistent with the important role of FOXO1 in p27 kip1 transcription, stimulated
      Vav1(-/-) T cells failed to down-regulate the expression of p27 kip1, explaining
      their G0-G1 arrest. These defects were more pronounced in Vav1/Vav3 double
      deficient T cells, suggesting partial redundancy between Vav1 and Vav3.
      Importantly, IL-2-induced p27 kip1 down-regulation and cyclin D3 up-regulation
      and FOXO1 phosphorylation were similar in Vav1(-/-) and wild-type T lymphoblasts,
      indicating that defective FOXO1 phosphorylation and p27 kip1 and cyclin D3
      expression do not result from deficient IL-2 signaling in the absence of Vav1.
      Thus, Vav1 is a critical regulator of a PI3K/Akt/FOXO1 pathway, which controls T
      cell cycle progression and proliferation.

PMID- 17015686
TI  - A preferential role for STAT5, not constitutively active STAT3, in promoting
      survival of a human lymphoid tumor.
AB  - STATs are believed to play key roles in normal and abnormal cell function. In the
      present work, we investigated the role of STATs in an IL-2-responsive human
      lymphoblastic lymphoma-derived cell line, YT. Only STAT3 was found constitutively
      tyrosine phosphorylated, but not other STATs. Hyperactive STAT3 was not
      attributable to a pre-existing intermediate affinity IL-2R complex and/or
      hyperactive Jak activity. Depletion of STAT3 protein expression reduced tumor
      cell viability with protracted kinetics (72-96 h), while TUNEL assays
      demonstrated cell death occurred via apoptosis. Interestingly, depletion of STAT5
      in this same tumor induced more pronounced cell death compared with STAT3
      depletion (24 h). Although IL-2 was able to rescue STAT3-depleted cells from
      death, it could not compensate for the loss of STAT5. To determine the
      prosurvival function of STAT3 vs STAT5 within the same tumor model, genes were
      profiled in STAT3- or STAT5-depleted YT cells by apoptosis-specific microarrays.
      Several differentially expressed genes were identified. Interestingly, those
      genes involved in NF-kappaB regulation, such as TNFR-associated factors 2 and 5
      and B cell leukemia/lymphoma 10, were readily decreased upon STAT5, but not
      STAT3, depletion as validated by quantitative RT-PCR. These results suggest that
      STAT5 and, to a lesser extent, hyperactive STAT3 provide preferential and
      critical cell survival signals for certain human lymphoid tumors, indicating that
      nonhyperactive STATs should be considered as therapeutic targets for abrogating
      tumorigenesis.

PMID- 17015687
TI  - Evidence for a role for notch signaling in the cytokine-dependent survival of
      activated T cells.
AB  - Peripheral T cell homeostasis results from a balance between factors promoting
      survival and those that trigger deletion of Ag-reactive cells. The cytokine IL-2
      promotes T cell survival whereas reactive oxygen species (ROS) sensitize T cells
      to apoptosis. Two pathways of activated T cell apoptosis-one triggered by Fas
      ligand and the other by cytokine deprivation-depend on ROS, with the latter also
      regulated by members of the Bcl-2 family. Notch family proteins regulate several
      cell-fate decisions in metazoans. Ectopic expression of the Notch1 intracellular
      domain (NICD) in T cells inhibits Fas-induced apoptosis. The underlying mechanism
      is not known and the role, if any, of Notch in regulating apoptosis triggered by
      cytokine deprivation or neglect has not been examined. In this study, we use a
      Notch1/Fc chimera; a blocking Ab to Notch1 and chemical inhibitors of gamma
      secretase to investigate the role of Notch signaling in activated T cells of
      murine origin. We show that perturbing Notch signaling in activated CD4+/CD8+ T
      cells maintained in IL-2 results in the accumulation of ROS, reduced Akt/protein
      kinase B activity, and expression of the antiapoptotic protein Bcl-xL,
      culminating in apoptosis. A broad-spectrum redox scavenger inhibits apoptosis but
      T cells expressing mutant Fas ligand are sensitive to apoptosis. Activated T
      cells isolated on the basis of Notch expression (Notch+) are enriched for Bcl-xL
      expression and demonstrate reduced susceptibility to apoptosis triggered by
      neglect or oxidative stress. Furthermore, enforced expression of NICD protects
      activated T cells from apoptosis triggered by cytokine deprivation. Taken
      together, these data implicate Notch1 signaling in the cytokine-dependent
      survival of activated T cells.

PMID- 17015688
TI  - Identification of a novel human granzyme B inhibitor secreted by cultured sertoli
      cells.
AB  - Sertoli cells have long since been recognized for their ability to suppress the
      immune system and protect themselves as well as other cell types from harmful
      immune reaction. However, the exact mechanism or product produced by Sertoli
      cells that affords this immunoprotection has never been fully elucidated. We
      examined the effect of mouse Sertoli cell-conditioned medium on human granzyme B
      mediated killing and found that there was an inhibitory effect. We subsequently
      found that a factor secreted by Sertoli cells inhibited killing through the
      inhibition of granzyme B enzymatic activity. SDS-PAGE analysis revealed that this
      factor formed an SDS-insoluble complex with granzyme B. Immunoprecipitation and
      mass spectroscopic analysis of the complex identified a proteinase inhibitor,
      serpina3n, as a novel inhibitor of human granzyme B. We cloned serpina3n cDNA,
      expressed it in Jurkat cells, and confirmed its inhibitory action on granzyme B
      activity. Our studies have led to the discovery of a new inhibitor of granzyme B
      and have uncovered a new mechanism used by Sertoli cells for immunoprotection.

PMID- 17015689
TI  - Involvement of the IkappaB kinase (IKK)-related kinases tank-binding kinase
      1/IKKi and cullin-based ubiquitin ligases in IFN regulatory factor-3 degradation.
AB  - Activation of the innate arm of the immune system following pathogen infection
      relies on the recruitment of latent transcription factors involved in the
      induction of a subset of genes responsible for viral clearance. One of these
      transcription factors, IFN regulatory factor 3 (IRF-3), is targeted for
      proteosomal degradation following virus infection. However, the molecular
      mechanisms involved in this process are still unknown. In this study, we show
      that polyubiquitination of IRF-3 increases in response to Sendai virus infection.
      Using an E1 temperature-sensitive cell line, we demonstrate that
      polyubiquitination is required for the observed degradation of IRF-3.
      Inactivation of NEDD8-activating E1 enzyme also results in stabilization of IRF-3
      suggesting the NEDDylation also plays a role in IRF-3 degradation following
      Sendai virus infection. In agreement with this observation, IRF-3 is recruited to
      Cullin1 following virus infection and overexpression of a dominant-negative
      mutant of Cullin1 significantly inhibits the degradation of IRF-3 observed in
      infected cells. We also asked whether the C-terminal cluster of phosphoacceptor
      sites of IRF-3 could serve as a destabilization signal and we therefore measured
      the half-life of C-terminal phosphomimetic IRF-3 mutants. Interestingly, we found
      them to be short-lived in contrast to wild-type IRF-3. In addition, no
      degradation of IRF-3 was observed in TBK1(-/-) mouse embryonic fibroblasts. All
      together, these data demonstrate that virus infection stimulates a host cell
      signaling pathway that modulates the expression level of IRF-3 through its C
      terminal phosphorylation by the IkappaB kinase-related kinases followed by its
      polyubiquitination, which is mediated in part by a Cullin-based ubiquitin ligase.

PMID- 17015690
TI  - The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy
      Delta12,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell
      lymphoma apoptosis by PPARgamma-independent mechanisms.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription
      factor important for adipogenesis and more recently has been shown to be an
      anticancer target. PPARgamma ligands, including the endogenous ligand 15-deoxy
      Delta12,14-PGJ2 (15d-PGJ2) and synthetic ligands like ciglitazone and
      troglitazone, all induce apoptosis in normal and malignant human B lymphocytes,
      but the dependency of PPARgamma for apoptosis induction is unknown. In this
      study, we used a PPARgamma dominant-negative approach and a small molecule
      irreversible PPARgamma antagonist and found that these inhibitors prevented
      PPARgamma activation but did not prevent B cell apoptosis induced by 15d-PGJ2 or
      ciglitazone. In addition, a PPARgamma agonist that is a structural analog of 15d
      PGJ2, and lacks the electrophilic carbon of the 15d-PGJ2 cyclopentenone ring,
      activated PPARgamma but did not kill B lymphocytes, further supporting a non
      PPARgamma-mediated mechanism. To further investigate the apoptotic mechanism, the
      effects of 15d-PGJ2 and ciglitazone on reactive oxygen species were investigated.
      15d-PGJ2, but not ciglitazone, potently induced reactive oxygen species in B
      lymphocytes, implicating the reactive nature of the 15d-PGJ2 structure in the
      apoptosis mechanism. In addition, 15d-PGJ2 caused an almost complete depletion of
      intracellular glutathione. Moreover, incubation with glutathione reduced ethyl
      ester, an antioxidant, prevented apoptosis induced by 15d-PGJ2, but not by
      ciglitazone. These findings indicate that the expression of PPARgamma may not be
      predictive of whether a normal or malignant B lineage cell is sensitive to
      PPARgamma agonists. Furthermore, these new findings support continued
      investigation into the use of PPARgamma agonists as agents to attenuate normal B
      cell responses and as anti-B cell lymphoma agents.

PMID- 17015691
TI  - RANTES modulates TLR4-induced cytokine secretion in human peripheral blood
      monocytes.
AB  - Monocytes are the key regulators of joint inflammation and destruction in
      rheumatoid arthritis; hence, suppression of their recruitment into the joint may
      be therapeutically beneficial. Chemokines, including RANTES, are highly expressed
      in the joints of patient with rheumatoid arthritis, and they promote leukocyte
      trafficking into the synovial tissue. Because endogenous TLR4 ligands are
      expressed in the rheumatoid joint, the TLR4 ligand LPS was used to characterize
      the effects of RANTES on the TLR4-mediated induction of TNF-alpha and IL-6. Using
      peripheral blood (PB) monocytes, RANTES decreased LPS-induced IL-6
      transcriptionally, whereas TNF-alpha was suppressed at the posttranscriptional
      level. RANTES signaled through p38 MAPK, and this signaling was further enhanced
      by LPS stimulation in PB monocytes, resulting in the earlier and increased
      secretion of IL-10. Inhibition of p38 by short-interfering RNA or a chemical
      inhibitor, as well as neutralization of IL-10, reversed the RANTES-mediated
      suppression of LPS-induced IL-6 and TNF-alpha. Further, when rheumatoid arthritis
      synovial fluid was added to PB monocytes, the neutralization of RANTES in fluid
      reduced the LPS-induced IL-10 and increased TNF-alpha. In conclusion, the results
      of this study suggest that RANTES down-regulates TLR4 ligation-induced IL-6 and
      TNF-alpha secretion by enhancing IL-10 production in PB monocytes. These
      observations suggest that the therapeutic neutralization of RANTES, in addition
      to decreasing the trafficking of leukocytes, may have a proinflammatory effect at
      the site of established chronic inflammation.

PMID- 17015692
TI  - Levels of specific peptide-HLA class I complex predicts tumor cell susceptibility
      to CTL killing.
AB  - Recognition of tumor-associated Ags (TAAs) on tumor cells by CTLs and the
      subsequent tumor cell death are assumed to be dependent on TAA protein expression
      and to correlate directly with the level of peptide displayed in the binding site
      of the HLA class I molecule. In this study we evaluated whether the levels of Her
      2/neu protein expression on human tumor cell lines directly correlate with HLA
      A*0201/Her2/neu peptide presentation and CTL recognition. We developed a TCR
      mimic (TCRm) mAb designated 1B8 that specifically recognizes the HLA
      A2.1/Her2/neu peptide (369-377) (Her2(369)-A2) complex. TCRm mAb staining
      intensity varied for the five human tumor cell lines analyzed, suggesting
      quantitative differences in levels of the Her2(369)-A2 complex on these cells.
      Analysis of tumor cell lines pretreated with IFN-gamma and TNF-alpha for Her2/neu
      protein and HLA-A2 molecule expression did not reveal a direct correlation
      between the levels of Her2/neu Ag, HLA-A2 molecule, and Her2(369)-A2 complex
      expression. However, compared with untreated cells, cytokine-treated cell lines
      showed an increase in Her2(369)-A2 epitope density that directly correlated with
      enhanced tumor cell death (p = 0.05). Although a trend was observed between tumor
      cell lysis and the level of the Her2(369)-A2 complex for untreated cells, the
      association was not significant. These findings suggest that tumor cell
      susceptibility to CTL-mediated lysis may be predicted based on the level of
      specific peptide-MHC class I expression rather than on the total level of TAA
      expression. Further, these studies demonstrate the potential of the TCRm mAb for
      validation of endogenous HLA-peptide epitopes on tumor cells.

PMID- 17015693
TI  - H2-M3-restricted T cells participate in the priming of antigen-specific CD4+ T
      cells.
AB  - H2-M3-restricted CD8+ T cells provide early protection against bacterial
      infections. In this study, we demonstrate that activated H2-M3-restricted T cells
      provide early signals for efficient CD4+ T cell priming. C57BL/6 mice immunized
      with dendritic cells coated with the MHC class II-restricted listeriolysin O
      peptide LLO(190-201) (LLO) generated CD4+ T cells capable of responding to
      Listeria monocytogenes (LM) infection. Inclusion of a H2-M3-restricted formylated
      peptide fMIGWII (fMIG), but not MHC class Ia-restricted peptides, during
      immunization with LLO significantly increased IFN-gamma-producing CD4+ T cell
      numbers, which was associated with increased protection against LM infection.
      Studies with a CD4+ T cell-depleting mAb indicate that the reduction in bacterial
      load in fMIG plus LLO immunized mice is likely due to augmented numbers of LLO
      specific CD4+ T cells, generated with the help of H2-M3-restricted CD8+ T cells.
      We also found that augmentation of LLO-specific CD4+ T lymphocytes with H2-M3
      restricted T cells requires presentation of LLO and fMIG by the same dendritic
      cells. Interestingly, the augmented CD4+ T cell response generated with fMIG also
      increased primary LM-specific responses by MHC class Ia-restricted CD8 T cells.
      Coimmunization with LLO and fMIG also increases the number of memory Ag-specific
      CD4+ T cells. We also demonstrate that CD8 T cells restricted to another MHC
      class Ib molecule, Qa-1, whose human equivalent is HLA-E, are also able to
      enhance Ag-specific CD4+ T cell responses. These results reveal a novel function
      for H2-M3- and Qa-1-restricted T cells; provision of help to CD4+ Th cells during
      the primary response.

PMID- 17015694
TI  - A 20-Mb region of chromosome 4 controls TNF-alpha-mediated CD8+ T cell aggression
      toward beta cells in type 1 diabetes.
AB  - Identification of candidate genes and their immunological mechanisms that control
      autoaggressive T cells in inflamed environments, may lead to novel therapies for
      autoimmune diseases, like type 1 diabetes (T1D). In this study, we used
      transgenic NOD mice that constitutively express TNF-alpha in their islets from
      neonatal life (TNF-alpha-NOD) to identify protective alleles that control T1D in
      the presence of a proinflammatory environment. We show that TNF-alpha-mediated
      breakdown in T cell tolerance requires recessive NOD alleles. To identify some of
      these recessive alleles, we crossed TNF-alpha-NOD mice to diabetes-resistant
      congenic NOD mice having protective alleles at insulin-dependent diabetes (Idd)
      loci that control spontaneous T1D at either the preinsulitis (Idd3.Idd5) or
      postinsulitis (Idd9) phases. No protection from TNF-alpha-accelerated T1D was
      afforded by resistance alleles at Idd3.Idd5. Lack of protection was not at the
      level of T cell priming, the efficacy of islet-infiltrating APCs to present islet
      peptides, nor the ability of high levels of CD4+ Foxp3+ T cells to accumulate in
      the islets. In contrast, protective alleles at Idd9 significantly increased the
      age at which TNF-alpha-NOD mice developed T1D. Disease delay was associated with
      a decreased ability of CD8+ T cells to respond to islet Ags presented by islet
      infiltrating APCs. Finally, we demonstrate that the protective region on
      chromosome 4 that controls T1D in TNF-alpha-Idd9 mice is restricted to the Idd9.1
      region. These data provide new evidence of the mechanisms by which selective
      genetic loci control autoimmune diseases in the presence of a strong inflammatory
      assault.

PMID- 17015695
TI  - Selective availability of IL-2 is a major determinant controlling the production
      of CD4+CD25+Foxp3+ T regulatory cells.
AB  - The development and maintenance of T regulatory (Treg) cells critically depend on
      IL-2. This requirement for IL-2 might be due to specificity associated with IL-2R
      signal transduction or because IL-2 was uniquely present in the niche in which
      Treg cells reside. To address this issue, we examined the capacity of IL-7R
      dependent signaling to support Treg cell production and prevent autoimmunity in
      IL-2Rbeta(-/-) mice. Expression of transgenic wild-type IL-7R or a chimeric
      receptor that consisted of the extracytoplasmic domain of the IL-7R alpha-chain
      and the cytoplasmic domain of IL-2R beta-chain in IL-2Rbeta(-/-) mice did not
      prevent autoimmunity. Importantly, expression of a chimeric receptor that
      consisted of the extracytoplasmic domain of the IL-2R beta-chain and the
      cytoplasmic domain of IL-7R alpha-chain in IL-2Rbeta(-/-) mice led to Treg cells
      production in the thymus and periphery and prevented autoimmunity. Signaling
      through the IL-2R or chimeric IL-2Rbeta/IL-7Ralpha in vivo or the culture of
      thymocytes from IL-2Rbeta(-/-) mice with IL-7 led to up-regulation of Foxp3 and
      CD25 on Treg cells. These findings indicate that IL-7R signal transduction is
      competent to promote Treg cell production, but this signaling requires triggering
      through IL-2 by binding to the extracytoplasmic portion of the IL-2R via this
      chimeric receptor. Thus, a major factor controlling the nonredundant activity of
      the IL-2R is selective compartmentalization of IL-2-producing cells with Treg
      cells in vivo.

PMID- 17015696
TI  - The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and
      differentiation of Th cells.
AB  - The role of PI3K in T cell activation and costimulation has been controversial.
      We previously reported that a kinase-inactivating mutation (D910A) in the
      p110delta isoform of PI3K results in normal T cell development, but impaired TCR
      stimulated cell proliferation in vitro. This proliferative defect can be overcome
      by providing CD28 costimulation, which raises the question as to whether
      p110delta activity plays a role in T cell activation in vivo, which occurs
      primarily in the context of costimulation. In this study, we show that the PI3K
      signaling pathway in CD28-costimulated p110delta D910A/D910A T cells is impaired,
      but that ERK phosphorylation and NF-kappaB nuclear translocation are unaffected.
      Under in vitro conditions of physiological Ag presentation and costimulation,
      p110delta D910A/D910A T cells showed normal survival, but underwent fewer
      divisions. Differentiation along the Th1 and Th2 lineages was impaired in
      p110delta D910A/D910A T cells and could not be rescued by exogenous cytokines in
      vitro. Adoptive transfer and immunization experiments in mice revealed that
      clonal expansion and differentiation in response to Ag and physiological
      costimulation were also compromised. Thus, p110delta contributes significantly to
      Th cell expansion and differentiation in vitro and in vivo, also in the context
      of CD28 costimulation.

PMID- 17015697
TI  - Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion.
AB  - Protein organization on the membrane of target cells may modulate HIV-1
      transmission. Since the tetraspanin CD81 is associated to CD4, the receptor of
      HIV-1 envelope protein (Env; gp120/gp41), we have explored the possibility that
      this molecule may modulate the initial steps of HIV-1 infection. On the other
      hand, CD81 belongs to the tetraspanin family, which has been described as
      organizers of protein microdomains on the plasma membrane. Therefore, the role of
      CD81 and other related tetraspanin, CD9, on the cell-to-cell fusion process
      mediated by HIV-1 was studied. We found that anti-tetraspanin Abs enhanced the
      syncytia formation induced by HIV-1 envelope proteins and viral entry in human T
      lymphoblasts. In addition, anti-CD81 Abs triggered its clustering in patches,
      where CD4 and CXCR4 were included. Moreover, the knocking down of CD81 and CD9
      expression resulted in an increase in syncytia formation and viral entry.
      Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to
      Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an
      important role in membrane fusion induced by HIV-1 envelope.

PMID- 17015698
TI  - IL-10- and IL-12-independent down-regulation of allergic sensitization by
      stimulation of CD40 signaling.
AB  - Interaction between CD154 (CD40 ligand) on activated T lymphocytes and its
      receptor CD40 has been shown to be critically involved in the generation of cell
      mediated as well as humoral immunity. CD40 triggering activates dendritic cells
      (DC), enhances their cytokine production, up-regulates the expression of
      costimulatory molecules, and induces their maturation. It is unknown how
      stimulation of CD40 during sensitization to an airborne allergen may affect the
      outcome of allergic airway inflammation. We took advantage of a mouse model of
      allergic asthma and a stimulatory mAb to CD40 (FGK45) to study the effects of
      CD40-mediated DC activation on sensitization to OVA and subsequent development of
      OVA-induced airway inflammation. Agonistic anti-CD40 mAb (FGK45) injected during
      sensitization with OVA abrogated the development of allergic airway inflammation
      upon repeated airway challenges with OVA. Inhibition of bronchial eosinophilia
      corresponded with reduced Th2 cytokine production and was independent of IL-12,
      as evidenced by a similar down-regulatory effect of anti-CD40 mAb in IL-12 p40
      deficient mice. In addition, FGK45 equally down-regulated allergic airway
      inflammation in IL-10-deficient mice, indicating an IL-10-independent mechanism
      of action of FGK45. In conclusion, our results show that CD40 signaling during
      sensitization shifts the immune response away from Th2 cytokine production and
      suppresses allergic airway inflammation in an IL-12- and IL-10-independent way,
      presumably resulting from enhanced DC activation during sensitization.

PMID- 17015699
TI  - High cytotoxic and specific migratory potencies of senescent CD8+ CD57+ cells in
      HIV-infected and uninfected individuals.
AB  - CD8+ CD57+ T lymphocytes, present at low levels in the peripheral blood of
      healthy individuals expand during HIV infection and remain elevated during
      chronic infection. Their role in the immune response remains unclear. We
      performed a large-scale gene array analysis (3158 genes) to characterize them
      and, interestingly, found no distinction in the transcriptional profiles of CD8+
      CD57+ T lymphocytes from HIV-infected and uninfected subjects. In both groups,
      these cells showed specificity for multiple Ags and produced large amounts of IFN
      gamma and TNF-alpha. The transcriptional profiles of CD8+ CD57+ and CD8+ CD57-
      cells, however, differed substantially. We propose that CD8+ CD57+ cells were Ag
      driven effector cells with very high cytotoxic effector potential including
      perforin, granzymes, and granulysin, regardless of HIV status. At both the
      messenger and protein levels, they expressed more adhesion molecules and fewer
      chemokine receptors (CCR7 and CXCR4) than CD8+ CD57- cells but expressed
      preferentially CX3CR1. The lower expression level of genes involved in cell cycle
      regulation showed limited proliferation capacities of CD8+ CD57+ even in response
      to TCR and IL-2, IL-7, and IL-15 stimulation. CD8+ CD57+ T cells from both HIV
      and uninfected subjects maintain effective cytotoxic potentials but are destined
      to migrate to nonlymphoid tissues without further cycling.

PMID- 17015700
TI  - A novel mechanism for complement activation at the surface of B cells following
      antigen binding.
AB  - Coligation of CD21 with BCR on the surface of B cells provides a costimulatory
      signal essential for efficient Ab responses to T-dependent Ags. To achieve this,
      Ag must be directly linked to C3 fragments, but how this occurs in vivo is not
      fully understood. Using BCR transgenic mice, we demonstrated that C3 was
      deposited on the surface of B cells following both high- and moderate-affinity Ag
      binding. This was dependent on the specific binding of IgM to the BCR-bound Ag
      and can occur independently of soluble immune complex formation. Based on these
      data, we propose a novel model in which immune complexes can form directly on the
      surface of the B cell following Ag binding. This model has implications for our
      understanding of B lymphocyte activation.

PMID- 17015701
TI  - Autophagy is induced in CD4+ T cells and important for the growth factor
      withdrawal cell death.
AB  - Autophagy is a tightly regulated catabolic mechanism that degrades proteins and
      organelles. Autophagy mediates programmed cell death under certain conditions. To
      determine the role of autophagy in T cells, we examined, in mouse CD4+ T cells,
      conditions under which autophagy is induced and alterations of the cell fate when
      autophagy is blocked. We have found that resting naive CD4+ T cells do not
      contain detectable autophagosomes. Autophagy can be observed in activated CD4+ T
      cells upon TCR stimulation, cytokine culturing, and prolonged serum starvation.
      Induction of autophagy in T cells requires JNK and the class III PI3K. Autophagy
      is inhibited by caspases and mammalian target of rapamycin in T cells.
      Interestingly, more Th2 cells than Th1 cells undergo autophagy. Th2 cells become
      more resistant to growth factor-withdrawal cell death when autophagy is blocked
      using either chemical inhibitors 3-methyladenine, or by RNA interference
      knockdown of beclin 1 and Atg7. Therefore, autophagy is an important mechanism
      that controls homeostasis of CD4+ T cells.

PMID- 17015702
TI  - The cyclin-dependent kinase inhibitor p27kip1 is required for transplantation
      tolerance induced by costimulatory blockade.
AB  - The cyclin-dependent kinase (CDK) inhibitor p27kip1 is an important negative
      regulator of the cell cycle that sets a threshold for mitogenic signals in T
      lymphocytes, and is required for T cell anergy in vitro. To determine whether
      p27(kip1) is required for tolerance in vivo, we performed cardiac allograft
      transplantation under conditions of combined CD28/CD40L costimulatory blockade.
      Although this treatment induced long-term allograft survival in wild-type
      recipients, costimulatory blockade was no longer sufficient to induce tolerance
      in mice lacking p27kip1. Rejected allografts from p27kip1-/- mice contained more
      CD4+ T lymphocytes and exhibited more tissue damage than allografts from
      tolerant, wild-type mice. Infiltrating p27kip1-deficient T cells, but not wild
      type T cells, exhibited nuclear expression of cyclins E and A, indicating
      uncontrolled T cell cycle progression in the graft. The failure of tolerance in
      p27kip1-/- mice was also accompanied by markedly increased numbers of
      allospecific, IFN-gamma-producing cells in the periphery, and occurred despite
      apparently normal regulatory T cell activity. These data demonstrate that the CDK
      inhibitor p27kip1 enforces the costimulatory requirement for the expansion and
      differentiation of alloimmune effector T lymphocytes in vivo, and point to CDKs
      as novel targets for immunosuppressive or tolerance-inducing therapies.

PMID- 17015703
TI  - The Src homology 2 domain-containing leukocyte protein of 76-kDa adaptor links
      integrin ligation with p44/42 MAPK phosphorylation and podosome distribution in
      murine dendritic cells.
AB  - The Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an
      important molecular intermediate in multiple signaling pathways governing immune
      cell function. In this study, we report that SLP-76 is expressed in CD11c+ B220-
      dendritic cells (DCs) isolated from murine thymus or spleen, and that SLP-76 is
      rapidly phosphorylated on tyrosine residues upon plating of bone marrow-derived
      DCs (BMDCs) on integrin agonists. SLP-76 is not required for the in vitro or in
      vivo generation of DCs, but SLP-76-deficient BMDCs adhere poorly to fibronectin,
      suggesting impaired integrin function. Consistent with impaired adhesion,
      cutaneous SLP-76-deficient DCs leave ear tissue at an elevated frequency compared
      with wild-type DCs. In addition, the pattern and distribution of actin-based
      podosome formation are visibly altered in BMDCs lacking SLP-76 following integrin
      engagement. SLP-76-deficient BMDCs manifest multiple signaling defects following
      integrin ligation, including reduced global tyrosine phosphorylation and markedly
      impaired phosphorylation of p44/42 MAPK (ERK1/2). These data implicate SLP-76 as
      an important molecular intermediate in the signaling pathways regulating multiple
      integrin-dependent DC functions, and add to the growing body of evidence that
      hemopoietic cells may use unique molecular intermediates and mechanisms for
      regulating integrin signaling.

PMID- 17015704
TI  - Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice
      with defective cystic fibrosis transmembrane conductance regulator.
AB  - Cystic fibrosis (CF) lung disease is characterized by persistent airway
      inflammation and airway infection that ultimately leads to respiratory failure.
      Aspergillus sp. are present in the airways of 20-40% of CF patients and are of
      unclear clinical significance. In this study, we demonstrate that CF
      transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftr(tm1Unc
      )TgN(fatty acid-binding protein)CFTR) and mutant (DeltaF508) mice develop
      profound lung inflammation in response to Aspergillus fumigatus hyphal Ag
      exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response
      to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in
      serum. In contrast, CFTR deficiency does not promote a Th1 immune response.
      Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice
      produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T
      cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates
      with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the
      Th1/Th2 balance in CD4+ T cells.

PMID- 17015705
TI  - Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN
      alpha.
AB  - The role of type I IFN in Th1 development, STAT4 activation, and IFN-gamma
      production in murine T cells has remained unresolved despite extensive
      examination. Initial studies indicated that IFN-alpha induced Th1 development and
      IFN-gamma production in human, but not murine, T cells, suggesting species
      specific differences in signaling. Later studies suggested that IFN-alpha also
      induced Th1 development in mice, similar to IL-12. More recent studies have
      questioned whether IFN-alpha actually induces Th1 development even in the human
      system. In the present study, we compared the capacity of IL-12 and IFN-alpha to
      induce Th1 differentiation, STAT4 phosphorylation, and IFN-gamma production in
      murine T cells. First, we show that IFN-alpha, in contrast to IL-12, cannot
      induce Th1 development. However, in differentiated Th1 cells, IFN-alpha can
      induce transient, but not sustained, STAT4 phosphorylation and, in synergy with
      IL-18, can induce transient, but not sustained, IFN-gamma production in Th1
      cells, in contrast to the sustained actions of IL-12. Furthermore, loss of STAT1
      increases IFN-alpha-induced STAT4 phosphorylation, but does not generate levels
      of STAT4 activation or IFN-gamma production achieved by IL-12 or convert
      transient STAT4 activation into a sustained response. Our findings agree with
      recent observations in human T cells that IFN-alpha-induced STAT4 activation is
      transient and unable to induce Th1 development, and indicate that IFN-alpha may
      act similarly in human and murine T cells.

PMID- 17015706
TI  - Establishment of lymphotoxin beta receptor signaling-dependent cell lines with
      follicular dendritic cell phenotypes from mouse lymph nodes.
AB  - Follicular dendritic cells (FDCs) have been shown to play a crucial role in the
      positive selection of high-affinity B cells that are generated by somatic
      hypermutation in germinal center (GC). Because of technical difficulties in
      preparing and maintaining pure FDCs, a role for FDCs in this complicated process
      has not been fully elucidated. In this study, we established a cell line
      designated as pFL that retained major FDC phenotypes from a three-dimensional
      culture of mouse lymph node cells. pFL cells proliferated slowly in response to
      an agonistic anti-lymphotoxin beta receptor mAb and TNF-alpha. A more rapidly
      growing clone, named FL-Y, with similar requirements for growth was isolated from
      a long-term culture of pFL. Analysis of surface markers in these two cell lines
      by immunostaining, flow cytometry, and DNA microarray revealed the expression of
      genes, including those of CD21, FcgammaRIIB, lymphotoxin beta receptor, ICAM-1,
      VCAM-1, IL-6, and C4, which have been shown to be characteristic of FDCs. In
      addition, B cell-activating factor was expressed in these two cell lines. At the
      pFL or FL-Y:B cell ratio of 1:100, the cell lines markedly sustained B cell
      survival and Ab production during 2 wk of culture, while most B cells collapsed
      within 1 wk in the absence of the FDC-like cells. Interestingly, expression of
      typical GC markers, Fas and GL-7, was notably augmented in B cells that were
      cocultured with Th cells on these two cell lines. Thus, pFL and FL-Y cells may be
      useful for providing insight into the functional role for FDCs in GC.

PMID- 17015707
TI  - DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear
      stress mediated by the integrin alpha4beta1.
AB  - The alpha4beta1 integrin is an essential adhesion molecule for recruitment of
      circulating lymphocytes into lymphoid organs and peripheral sites of
      inflammation. Chemokines stimulate alpha4beta1 adhesive activity allowing
      lymphocyte arrest on endothelium and subsequent diapedesis. Activation of the
      GTPase Rac by the guanine-nucleotide exchange factor Vav1 promoted by CXCL12
      controls T lymphocyte adhesion mediated by alpha4beta1. In this study, we
      investigated the role of DOCK2, a lymphocyte guanine-nucleotide exchange factor
      also involved in Rac activation, in CXCL12-stimulated human T lymphocyte adhesion
      mediated by alpha4beta1. Using T cells transfected with DOCK2 mutant forms
      defective in Rac activation or with DOCK2 small interfering RNA, we demonstrate
      that DOCK2 is needed for efficient chemokine-stimulated lymphocyte attachment to
      VCAM-1 under shear stress. Flow chamber, soluble binding, and cell spreading
      assays identified the strengthening of alpha4beta1-VCAM-1 interaction, involving
      high affinity alpha4beta1 conformations, as the adhesion step mainly controlled
      by DOCK2 activity. The comparison of DOCK2 and Vav1 involvement in CXCL12
      promoted Rac activation and alpha4beta1-dependent human T cell adhesion indicated
      a more prominent role of Vav1 than DOCK2. These results suggest that DOCK2
      mediated signaling regulates chemokine-stimulated human T lymphocyte alpha4beta1
      adhesive activity, and that cooperation with Vav1 might be required to induce
      sufficient Rac activation for efficient adhesion. In contrast, flow chamber
      experiments using lymph node and spleen T cells from DOCK2(-/-) mice revealed no
      significant alterations in CXCL12-promoted adhesion mediated by alpha4beta1,
      indicating that DOCK2 activity is dispensable for triggering of this adhesion in
      mouse T cells, and suggesting that Rac activation plays minor roles in this
      process.

PMID- 17015709
TI  - Kinetics of human B cell behavior and amplification of proliferative responses
      following stimulation with IL-21.
AB  - Although recent studies indicated that IL-21 is an important regulator of human B
      cell activation, detailed comparison of the effects of IL-21 on distinct B cell
      subsets have not been performed. Our studies revealed that IL-21R is expressed by
      naive and germinal center B cells, but not memory or plasma cells. IL-21R was
      increased on naive and memory B cells following in vitro activation.
      Investigation into the kinetics and magnitude of responses of human B cells to IL
      21 revealed that IL-21 potently augmented proliferation of CD40L-stimulated
      neonatal, splenic naive, and memory and tonsil germinal center B cells. This
      response exceeded that induced by IL-4, IL-10, and IL-13, cytokines that also
      induce B cell proliferation. Remarkably, CD40L/IL-21-stimulated naive B cells
      underwent the same number of divisions as memory cells and exhibited a greater
      enhancement in their response compared with CD40L alone than memory B cells.
      Therefore, IL-21 is a powerful growth factor for naive B cells. This may result
      from the higher expression of IL-21R on naive, compared with memory, B cells.
      Stimulation of human B cells with CD40L/IL-21 also induced IL-10 production and
      activation of STAT3. We propose that IL-21 may have therapeutic application in
      conditions of immunodeficiency where it could expand naive B cells, the
      predominant B cell subset in such patients. Conversely, because IL-21 is
      increased in murine models of lupus, dysregulated IL-21 production may contribute
      to perturbed B cell homeostasis observed in systemic lupus erythematosus. Thus,
      antagonizing IL-21 may be a novel strategy for treating Ab-mediated autoimmune
      diseases.

PMID- 17015708
TI  - Expression of CD1d molecules by human schwann cells and potential interactions
      with immunoregulatory invariant NK T cells.
AB  - CD1d-restricted NKT cells expressing invariant TCR alpha-chains (iNKT cells)
      produce both proinflammatory and anti-inflammatory cytokines rapidly upon
      activation, and are believed to play an important role in both host defense and
      immunoregulation. To address the potential implications of iNKT cell responses
      for infectious or inflammatory diseases of the nervous system, we investigated
      the expression of CD1d in human peripheral nerve. We found that CD1d was
      expressed on the surface of Schwann cells in situ and on primary or immortalized
      Schwann cell lines in culture. Schwann cells activated iNKT cells in a CD1d
      dependent manner in the presence of alpha-galactosylceramide. Surprisingly, the
      cytokine production of iNKT cells stimulated by alpha-galactosylceramide
      presented by CD1d+ Schwann cells showed a predominance of Th2-associated
      cytokines such as IL-5 and IL-13 with a marked deficiency of proinflammatory Th1
      cytokines such as IFN-gamma or TNF-alpha. Our findings suggest a mechanism by
      which iNKT cells may restrain inflammatory responses in peripheral nerves, and
      raise the possibility that the expression of CD1d by Schwann cells could be
      relevant in the pathogenesis of infectious and inflammatory diseases of the
      peripheral nervous system.

PMID- 17015710
TI  - Modulation of airway remodeling and airway inflammation by peroxisome
      proliferator-activated receptor gamma in a murine model of toluene diisocyanate
      induced asthma.
AB  - Toluene diisocyanate (TDI) is a leading cause of occupational asthma. Although
      considerable controversy remains regarding its pathogenesis, TDI-induced asthma
      is an inflammatory disease of the airways characterized by airway remodeling.
      Peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to
      play a critical role in the control of airway inflammatory responses. However, no
      data are available on the role of PPARgamma in TDI-induced asthma. We have used a
      mouse model for TDI-induced asthma to determine the effect of PPARgamma agonist,
      rosiglitazone, or pioglitazone, and PPARgamma on TDI-induced bronchial
      inflammation and airway remodeling. This study with the TDI-induced model of
      asthma revealed the following typical pathophysiological features: increased
      numbers of inflammatory cells of the airways, airway hyperresponsiveness,
      increased levels of Th2 cytokines (IL-4, IL-5, and IL-13), adhesion molecules
      (ICAM-1 and VCAM-1), chemokines (RANTES and eotaxin), TGF-beta1, and NF-kappaB in
      nuclear protein extracts. In addition, the mice exposed to TDI developed features
      of airway remodeling, including thickening of the peribronchial smooth muscle
      layer, subepithelial collagen deposition, and increased airway mucus production.
      Administration of PPARgamma agonists or adenovirus carrying PPARgamma2 cDNA
      reduced the pathophysiological symptoms of asthma and decreased the increased
      levels of Th2 cytokines, adhesion molecules, chemokines, TGF-beta1, and NF-kappaB
      in nuclear protein extracts after TDI inhalation. In addition, inhibition of NF
      kappaB activation decreased the increased levels of Th2 cytokines, adhesion
      molecules, chemokines, and TGF-beta1 after TDI inhalation. These findings
      demonstrate a protective role of PPARgamma in the pathogenesis of the TDI-induced
      asthma phenotype.

PMID- 17015711
TI  - IL-4-secreting NKT cells prevent hypersensitivity pneumonitis by suppressing IFN
      gamma-producing neutrophils.
AB  - Hypersensitivity pneumonitis (HP) is mediated by Th1 immune response. NKT cells
      regulate immune responses by modulating the Th1/Th2 balance. Therefore, we
      postulated that NKT cells play a critical role in the development of the HP by
      modulating the Th1/Th2 response. To address this issue, we explored the
      functional roles of NKT cells in Saccharopolyspora rectivirgula (SR)-induced HP.
      In CD1d(-/-) mice, the HP was worse in terms of histological changes,
      hydroxyproline levels, the CD4:CD8 ratio in bronchoalveolar lavage fluid, and SR
      specific immune responses than in control mice. CD1d(-/-) mice showed elevated
      IFN-gamma production in the lung during the HP, and this was produced mainly by
      Gr-1+ neutrophils. The blockade of IFN-gamma in CD1d(-/-) mice attenuated the HP,
      whereas the injection of rIFN-gamma aggravated it. Moreover, the depletion of Gr
      1+ neutrophils reduced CD8+ T cell numbers in bronchoalveolar lavage fluid during
      the HP. The adoptive transfer of IL-4(-/-) mouse NKT cells did not attenuate the
      HP, whereas wild-type or IFN-gamma(-/-) mouse NKT cells suppressed the HP. In
      conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by
      suppressing IFN-gamma-producing neutrophils, which induce the activation and
      proliferation of CD8+ T cells in the lung.

PMID- 17015712
TI  - Innate response to focal necrotic injury inside the blood-brain barrier.
AB  - We have studied the initial innate immune response to focal necrotic injury on
      different sides of the mouse blood-brain barrier by two-photon intravital
      microscopy. Transgenic mice in which the promoter of the myeloid isoform of
      lysozyme drives GFP were used to track granulocytes and monocytes. Necrotic
      injury in the meninges, but not the brain parenchyma, recruited GFP+ cells within
      minutes that fully surrounded the necrotic site within a day. Recently, it has
      been suggested that microglial cells and astrocytes cooperate to mount a distinct
      response to laser injury behind the blood-brain barrier. We followed the
      microglial response in heterozygous knockin mice in which GFP replaces CX3CR1
      coding sequence. Prior to injury, microglial cell bodies were immobile over days,
      but moved to the laser injury site within 1 day. We followed astrocytes, which
      have been proposed to cooperate with microglial cells in response to focal
      injury, using transgenic mice in which glial fibrillary acidic protein promoter
      drives GFP expression. Before injury fine astrocyte processes permeate the
      parenchyma. Astrocytes polarized toward the injury in an ATP, connexin
      hemichannels, and intracellular Ca2+ -dependent process. The astrocytes network
      established a cytoplasmic Ca2+ gradient that preceded the microglial response.
      This is consistent with astrocyte-microglial collaboration to mount this innate
      response that excludes blood leukocytes.

PMID- 17015713
TI  - Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune
      diabetes in mice.
AB  - Type 1 diabetes (T1D) is a disease caused by the destruction of the beta cells of
      the pancreas by activated T cells. Dendritic cells (DC) are the APC that initiate
      the T cell response that triggers T1D. However, DC also participate in T cell
      tolerance, and genetic engineering of DC to modulate T cell immunity is an area
      of active research. Galectin-1 (gal-1) is an endogenous lectin with regulatory
      effects on activated T cells including induction of apoptosis and down-regulation
      of the Th1 response, characteristics that make gal-1 an ideal transgene to
      transduce DC to treat T1D. We engineered bone marrow-derived DC to synthesize
      transgenic gal-1 (gal-1-DC) and tested their potential to prevent T1D through
      their regulatory effects on activated T cells. NOD-derived gal-1-DC triggered
      rapid apoptosis of diabetogenic BDC2.5 TCR-transgenic CD4+ T cells by TCR
      dependent and -independent mechanisms. Intravenously administered gal-1-DC
      trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and
      insulitis in the NODrag1(-/-) lymphocyte adoptive transfer model. The therapeutic
      effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells
      and reduced number of IFN-gamma-secreting CD4+ T cells in pancreatic lymph nodes.
      Treatment with gal-1-DC inhibited proliferation and secretion of IFN-gamma of T
      cells in response to beta cell Ag. Unlike other DC-based approaches to modulate T
      cell immunity, the use of the regulatory properties of gal-1-DC on activated T
      cells might help to delete beta cell-reactive T cells at early stages of the
      disease when the diabetogenic T cells are already activated.

PMID- 17015714
TI  - CXCR5 identifies a subset of Vgamma9Vdelta2 T cells which secrete IL-4 and IL-10
      and help B cells for antibody production.
AB  - Vgamma9Vdelta2 T lymphocytes recognize nonpeptidic Ags and mount effector
      functions in cellular immune responses against microorganisms and tumors, but
      little is known about their role in Ab-mediated immune responses. We show here
      that expression of CXCR5 identifies a unique subset of Vgamma9Vdelta2 T cells
      which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and
      IL-10 and help B cells for Ab production. These properties portray CXCR5+
      Vgamma9Vdelta2 T cells as a distinct memory T cell subset with B cell helper
      function.

PMID- 17015715
TI  - Suppression of experimental autoimmune myasthenia gravis by granulocyte
      macrophage colony-stimulating factor is associated with an expansion of FoxP3+
      regulatory T cells.
AB  - Dendritic cells (DCs) have the potential to activate or tolerize T cells in an Ag
      specific manner. Although the precise mechanism that determines whether DCs
      exhibit tolerogenic or immunogenic functions has not been precisely elucidated,
      growing evidence suggests that DC function is largely dependent on
      differentiation status, which can be manipulated using various growth factors. In
      this study, we investigated the effects of mobilization of specific DC subsets
      using GM-CSF and fms-like tyrosine kinase receptor 3-ligand (Flt3-L)-on the
      susceptibility to induction of experimental autoimmune myasthenia gravis (EAMG).
      We administered GM-CSF or Flt3-L to C57BL/6 mice before immunization with
      acetylcholine receptor (AChR) and observed the effect on the frequency and
      severity of EAMG development. Compared with AChR-immunized controls, mice treated
      with Flt3-L before immunization developed EAMG at an accelerated pace initially,
      but disease frequency and severity was comparable at the end of the observation
      period. In contrast, GM-CSF administered before immunization exerted a sustained
      suppressive effect against the induction of EAMG. This suppression was associated
      with lowered serum autoantibody levels, reduced T cell proliferative responses to
      AChR, and an expansion in the population of FoxP3+ regulatory T cells. These
      results highlight the potential of manipulating DCs to expand regulatory T cells
      for the control of autoimmune diseases such as MG.

PMID- 17015716
TI  - Absence of innate MyD88 signaling promotes inducible allograft acceptance.
AB  - Prior experimental strategies to induce transplantation tolerance have focused
      largely on modifying adaptive immunity. However, less is known concerning the
      role of innate immune signaling in the induction of transplantation tolerance.
      Using a highly immunogenic murine skin transplant model that resists
      transplantation tolerance induction when innate immunity is preserved, we show
      that absence of MyD88, a key innate Toll like receptor signal adaptor, abrogates
      this resistance and facilitates inducible allograft acceptance. In our model,
      absence of MyD88 impairs inflammatory dendritic cell responses that reduce T cell
      activation. This effect increases T cell susceptibility to suppression mediated
      by CD4+ CD25+ regulatory T cells. Therefore, this study provides evidence that
      absence of MyD88 promotes inducible allograft acceptance and implies that
      inhibiting innate immunity may be a potential, clinically relevant strategy to
      facilitate transplantation tolerance.

PMID- 17015717
TI  - SAP is required for Th cell function and for immunity to influenza.
AB  - Ab is a crucial component of protective immunity to infection, but Ab responses
      do not proceed normally when defects occur in a protein called signaling
      lymphocytic activation molecule-associated protein (SAP). To explain this Ab
      defect, we analyzed B cell and plasma cell responses under conditions of SAP
      deficiency. Our results demonstrate that SAP-deficient (SAP knockout (KO)) mice
      have a profound CD4 T cell-intrinsic defect in generating Ag-specific plasma
      cells following challenge with model Ags or influenza virus, resulting in low Ag
      specific Ab titers. We also show that SAP is required in CD4 T cells for normal
      division and expansion of B cells. These B cell and plasma cell defects were
      observed during the expansion phase of the primary immune response, indicating
      early defects in Th cell activity. In fact, additional experiments revealed a
      nearly complete lack of T cell help for B cells in SAP KO mice. Our work suggests
      that the ability of SAP to promote T-dependent humoral immune responses is
      important for antiviral immunity because mice lacking SAP are unable to prevent
      high dose secondary influenza infection, and because passive transfer of IgG in
      immune serum from wild-type, but not SAP KO mice can protect mice from an
      otherwise lethal influenza infection. Overall, our results demonstrate that SAP
      is required in CD4 T cells for their ability to help B cell responses and promote
      influenza-specific immunity.

PMID- 17015718
TI  - Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell
      death.
AB  - Galectin-1 kills immature thymocytes and activated peripheral T cells by binding
      to glycans on T cell glycoproteins including CD7, CD45, and CD43. Although roles
      for CD7 and CD45 in regulating galectin-1-induced death have been described, the
      requirement for CD43 remains unknown. We describe a novel role for CD43 in
      galectin-1-induced death, and the effects of O-glycan modification on galectin-1
      binding to CD43. Loss of CD43 expression reduced galectin-1 death of murine
      thymocytes and human T lymphoblastoid cells, indicating that CD43 is required for
      maximal T cell susceptibility to galectin-1. CD43, which is heavily O
      glycosylated, contributes a significant fraction of galectin-1 binding sites on T
      cells, as T cells lacking CD43 bound approximately 50% less galectin-1 than T
      cells expressing CD43. Although core 2 modification of O-glycans on other
      glycoprotein receptors is critical for galectin-1-induced cross-linking and T
      cell death, galectin-1 bound to CD43 fusion proteins modified with either
      unbranched core 1 or branched core 2 O-glycans and expression of core 2 O-glycans
      did not enhance galectin-1 binding to CD43 on T cells. Moreover, galectin-1
      binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T
      cell surface. Thus, CD43 bearing either core 1 or core 2 O-glycans can positively
      regulate T cell susceptibility to galectin-1, identifying a novel function for
      CD43 in controlling cell death. In addition, these studies demonstrate that
      different T cell glycoproteins on the same cell have distinct requirements for
      glycan modifications that allow recognition and cross-linking by galectin-1.

PMID- 17015719
TI  - ERK signaling is a molecular switch integrating opposing inputs from B cell
      receptor and T cell cytokines to control TLR4-driven plasma cell differentiation.
AB  - Differentiation of B cells into plasma cells represents a critical
      immunoregulatory checkpoint where neutralizing Abs against infectious agents must
      be selected whereas self-reactive Abs are suppressed. Bacterial LPS is a uniquely
      potent bacterial immunogen that can bypass self-tolerance within the T cell
      repertoire. We show here that during LPS-induced plasma cell differentiation, the
      ERK intracellular signaling pathway serves as a pivotal switch integrating
      opposing inputs from Ag via BCR and from the two best characterized B cell
      differentiation factors made by T cells, IL-2 and IL-5. Continuous Ag receptor
      signaling through the RAS/MEK/ERK pathway, as occurs in self-reactive B cells,
      inhibits LPS induction of Blimp-1 and the plasma cell differentiation program.
      Differentiation resumes after a transient pulse of Ag-ERK signaling, or upon
      inactivation of ERK by IL-2 and IL-5 through induction of dual-specificity
      phosphatase 5 (Dusp5). The architecture of this molecular switch provides a
      framework for understanding the specificity of antibacterial Ab responses and
      resistance to bacterially induced autoimmune diseases such as Guillain-Barre
      syndrome.

PMID- 17015720
TI  - A single polymorphism disrupts the killer Ig-like receptor 2DL2/2DL3 D1 domain.
AB  - Genetic polymorphisms found in the killer Ig-like receptor (KIR), two domains,
      long cytoplasmic tail 2/3 (KIR2DL2/3) locus are responsible for the differential
      binding of KIR2DL2/3 allelic products with their HLA-C ligands and have been
      associated with the resolution of hepatitis C infection. In our study, a KIR
      CD3zeta fusion-binding assay did not detect any interaction between the
      KIR2DL2*004 extracellular domain and several putative KIR2DL2/3 ligands. To
      determine the amino acid polymorphism(s) responsible for the KIR2DL2*004
      phenotype, we mutated the polymorphic residues of full-length KIR and expressed
      them in human Jurkat cells. Flow cytometry analysis failed to detect the surface
      expression of receptors containing a threonine at position 41 (T41), a
      polymorphism specific to KIR2DL2*004. Confocal microscopy showed that receptors
      containing T41 were retained inside the cell and had a perinuclear localization,
      possibly indicating that their extracellular domain was misfolded. Most KIR2DL2/3
      alleles possess an arginine at position 41 (R41), and we predicted through
      molecular modeling and demonstrated by mutagenesis that R41 most likely interacts
      with the nearby residues Y77 and D47. Interaction between these residues would
      maintain C strand contact with the C' and F strands of the D1 domain beta-sheet.
      Furthermore, R41 and Y77 are conserved in the C and F strand amino acid
      alignments of Ig-like superfamily members, and may therefore be necessary for the
      structural integrity of other immune response proteins. Our data indicate that
      the extracellular T41 polymorphism encoded by the KIR2DL2*004 allele most likely
      results in misfolding of the D1 domain and complete intracellular retention of
      the receptor.

PMID- 17015721
TI  - Stochastic monoallelic expression of IL-10 in T cells.
AB  - IL-10 is a potent anti-inflammatory and immunomodulatory cytokine, exerting major
      effects in the degree and quality of the immune response. Using a newly generated
      IL-10 reporter mouse model, which easily allows the study of IL-10 expression
      from each allele in a single cell, we report here for the first time that IL-10
      is predominantly monoallelic expressed in CD4+ T cells. Furthermore, we have
      compelling evidence that this expression pattern is not due to parental
      imprinting, allelic exclusion, or strong allelic bias. Instead, our results
      support a stochastic regulation mechanism, in which the probability to initiate
      allelic transcription depends on the strength of TCR signaling and subsequent
      capacity to overcome restrictions imposed by chromatin hypoacetylation. In vivo
      Ag-experienced T cells show a higher basal probability to transcribe IL-10 when
      compared with naive cells, yet still show mostly monoallelic IL-10 expression.
      Finally, statistical analysis on allelic expression data shows transcriptional
      independence between both alleles. We conclude that CD4+ T cells have a low
      probability for IL-10 allelic activation resulting in a predominantly monoallelic
      expression pattern, and that IL-10 expression appears to be stochastically
      regulated by controlling the frequency of expressing cells, rather than absolute
      protein levels per cell.

PMID- 17015722
TI  - Differential and nonredundant roles of phospholipase Cgamma2 and phospholipase
      Cgamma1 in the terminal maturation of NK cells.
AB  - NK cells play a central role in mediating innate immune responses. Activation of
      NK cells results in cytotoxicity, cytokine, and chemokine secretions. In this
      study, we show that in mice with targeted deletion of phospholipase Cgamma
      (PLCgamma)2, one of the key signal transducers, there are profound effects on the
      development and terminal maturation of NK cells. Lack of PLCgamma2 significantly
      impaired the ability of lineage-committed NK precursor cells to acquire subset
      specific Ly49 receptors and thereby terminal maturation of NK cells.
      Overexpression of isozyme, PLCgamma1, in PLCgamma2-deficient NK cells resulted in
      the successful Ly49 acquisition and terminal maturation of the NK cells; however,
      it could only partially rescue NKG2D-mediated cytotoxicity with no cytokine
      production. Furthermore, PLCgamma2-deficient NK cells failed to mediate antitumor
      cytotoxicity and inflammatory cytokine production, displaying a generalized
      hyporesponsiveness. Our results strongly demonstrate that PLCgamma1 and PLCgamma2
      play nonredundant and obligatory roles in NK cell ontogeny and in its effector
      functions.

PMID- 17015723
TI  - Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells
      versus suppression of proinflammatory cytokine production including IL-23-induced
      IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism.
AB  - Recent lines of evidence have demonstrated that IL-27, a newly identified IL-12
      related cytokine, has two apparently conflicting roles in immune responses: one
      as an initiator of Th1 responses and the other as an attenuator of inflammatory
      cytokine production. Although the IL-27-mediated Th1 initiation mechanism has
      been elucidated, little is known about the molecular basis for the suppression of
      cytokine production. In the present study, we demonstrated that IL-27 suppressed
      the production of various proinflammatory cytokines by fully activated CD4+ T
      cells while it had no effect on the cytokine production by CD4+ T cells at early
      phases of activation. IL-27 also suppressed IL-17 production by activated CD4+ T
      cells, thereby counteracting IL-23, another IL-12-related cytokine with
      proinflammatory effects. In fully activated CD4+ T cells, STAT3 was
      preferentially activated by IL-27 stimulation, whereas both STAT1 and 3 were
      activated by IL-27 in early activated CD4+ T cells. Lack of STAT3 in fully
      activated cells impaired the suppressive effects of IL-27. These data indicated
      that the preferential activation of STAT3 in fully activated CD4+ T cells plays
      an important role in the cytokine suppression by IL-27/WSX-1.

PMID- 17015724
TI  - Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double
      knockout mice.
AB  - Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by
      activation-induced cytosine deaminase (AID). The uracil, and potentially
      neighboring bases, are processed by error-prone base excision repair and mismatch
      repair. Deficiencies in Ung, Msh2, or Msh6 affect SHM and CSR. To determine
      whether Msh2/Msh6 complexes which recognize single-base mismatches and loops were
      the only mismatch-recognition complexes required for SHM and CSR, we analyzed
      these processes in Msh6(-/-)Ung(-/-) mice. SHM and CSR were affected in the same
      degree and fashion as in Msh2(-/-)Ung(-/-) mice; mutations were mostly C,G
      transitions and CSR was greatly reduced, making Msh2/Msh3 contributions unlikely.
      Inactivating Ung alone reduced mutations from A and T, suggesting that, depending
      on the DNA sequence, varying proportions of A,T mutations arise by error-prone
      long-patch base excision repair. Further, in Msh6(-/-)Ung(-/-) mice the 5' end
      and the 3' region of Ig genes was spared from mutations as in wild-type mice,
      confirming that AID does not act in these regions. Finally, because in the
      absence of both Ung and Msh6, transition mutations from C and G likely are
      "footprints" of AID, the data show that the activity of AID is restricted
      drastically in vivo compared with AID in cell-free assays.

PMID- 17015725
TI  - V(D)J recombinase-mediated processing of coding junctions at cryptic
      recombination signal sequences in peripheral T cells during human development.
AB  - V(D)J recombinase mediates rearrangements at immune loci and cryptic
      recombination signal sequences (cRSS), resulting in a variety of genomic
      rearrangements in normal lymphocytes and leukemic cells from children and adults.
      The frequency at which these rearrangements occur and their potential pathologic
      consequences are developmentally dependent. To gain insight into V(D)J
      recombinase-mediated events during human development, we investigated 265 coding
      junctions associated with cRSS sites at the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) locus in peripheral T cells from 111 children
      during the late stages of fetal development through early adolescence. We
      observed a number of specific V(D)J recombinase processing features that were
      both age and gender dependent. In particular, TdT-mediated nucleotide insertions
      varied depending on age and gender, including percentage of coding junctions
      containing N-nucleotide inserts, predominance of GC nucleotides, and presence of
      inverted repeats (Pr-nucleotides) at processed coding ends. In addition, the
      extent of exonucleolytic processing of coding ends was inversely related to age.
      We also observed a coding-partner-dependent difference in exonucleolytic
      processing and an age-specific difference in the subtypes of V(D)J-mediated
      events. We investigated these age- and gender-specific differences with
      recombination signal information content analysis of the cRSS sites in the human
      HPRT locus to gain insight into the mechanisms mediating these developmentally
      specific V(D)J recombinase-mediated rearrangements in humans.

PMID- 17015726
TI  - Transitional B cell fate is associated with developmental stage-specific
      regulation of diacylglycerol and calcium signaling upon B cell receptor
      engagement.
AB  - Functional peripheral mature follicular B (FoB) lymphocytes are thought to
      develop from immature transitional cells in a BCR-dependent manner. We have
      previously shown that BCR cross-linking in vitro results in death of early
      transitional (T1) B cells, whereas late transitional (T2) B cells survive and
      display phenotypic characteristics of mature FoB cells. We now demonstrate that
      diacylglycerol (DAG), a lipid second messenger implicated in cell survival and
      differentiation, is produced preferentially in T2 compared with T1 B cells upon
      BCR cross-linking. Consistently, inositol 1,4,5-triphosphate is also produced
      preferentially in T2 compared with T1 B cells. Unexpectedly, the initial calcium
      peak appears similar in both T1 and T2 B cells, whereas sustained calcium levels
      are higher in T1 B cells. Pretreatment with 2-aminoethoxydiphenylborate, an
      inhibitor of inositol 1,4,5-triphosphate receptor-mediated calcium release, and
      verapamil, an inhibitor of L-type calcium channels, preferentially affects T1 B
      cells, suggesting that distinct mechanisms regulate calcium mobilization in each
      of the two transitional B cell subsets. Finally, BCR-mediated DAG production is
      dependent upon Bruton's tyrosine kinase and phospholipase C-gamma2, enzymes
      required for the development of FoB from T2 B cells. These results suggest that
      calcium signaling in the absence of DAG-mediated signals may lead to T1 B cell
      tolerance, whereas the combined action of DAG and calcium signaling is necessary
      for survival and differentiation of T2 into mature FoB lymphocytes.

PMID- 17015727
TI  - Induced expression of murine gamma2a by CD40 ligation independently of IFN-gamma.
AB  - IgG2a, with gamma2a H chains, is important for protection against viruses and
      other intracellular pathogens. Although a large portion of IgG2a expression is
      dependent upon IFN-gamma, some germline transcription and switch recombination to
      the murine gamma2a H chain gene expression are independent of IFN-gamma. We found
      that agonistic anti-CD40 Abs injected into IFN-gamma-deficient mice induce a >
      200-fold increase in the amount of serum Ig2a, while other Ig isotypes are
      increased by 16-fold or less. In vitro, ligation of CD40 on B cells, without the
      addition of other B cell activators or cytokines, results in germline
      transcription and switch recombination that are largely restricted to the gamma2a
      gene. These results suggest that some immune responses to infectious agents can
      result in large amounts of IgG2a expression through ligation of CD40, without the
      expression of IFN-gamma by Th1 or other cells.

PMID- 17015728
TI  - Stage-specific expression of two neighboring Crlz1 and IgJ genes during B cell
      development is regulated by their chromatin accessibility and histone
      acetylation.
AB  - The IgJ gene is expressed in the plasma cell stage. However, its neighboring
      charged amino acid-rich leucine zipper 1 (Crlz1) gene, which is mapped 30 kb
      upstream of the IgJ gene in mice, is shown to be expressed in the pre-B cell
      stage. These stage-specific expressions of two neighboring genes are found to be
      regulated by their chromatin accessibility and acetylation. Hypersensitive site 1
      on the IgJ promoter is opened in the plasma cells, whereas hypersensitive sites
      9/10 on the Crlz1 promoter are opened in the pre-B cells. Furthermore, H3 and H4
      histones toward the chromatin of the Crlz1 gene are found to be hyperacetylated,
      especially on H3, in the pre-B cells, whereas those toward the chromatin of the
      IgJ gene are found to be hyperacetylated in the plasma cells. Consistently, the
      hyperacetylation of H3 and H4 toward the chromatin of the IgJ gene but not the
      Crlz1 gene is induced by an IL-2 treatment of BCL1, which is a model cell line
      for studying the terminal differentiation of B cells.

PMID- 17015729
TI  - The DMalpha and DMbeta chain cooperate in the oxidation and folding of HLA-DM.
AB  - HLA-DM (DM) is a heterodimeric MHC molecule that catalyzes the peptide loading of
      classical MHC class II molecules in the endosomal/lysosomal compartments of APCs.
      Although the function of DM is well-established, little is known about how
      DMalpha and beta-chains fold, oxidize, and form a complex in the endoplasmic
      reticulum (ER). In this study, we show that glycosylation promotes, but is not
      essential for, DMalphabeta ER exit. However, glycosylation of DMalpha N15 is
      required for oxidation of the alpha-chain. The DMalpha and beta-chains direct
      each others fate: single DMalpha chains cannot fully oxidize without DMbeta,
      while DMbeta forms disulfide-linked homodimers without DMalpha. Correct oxidation
      and subsequent ER egress depend on the unique DMbeta C25 and C35 residues. This
      suggests that the C25-C35 disulfide bond in the peptide-binding domain overcomes
      the need for stabilizing peptides required by other MHC molecules.

PMID- 17015730
TI  - Processing of a class I-restricted epitope from tyrosinase requires peptide N
      glycanase and the cooperative action of endoplasmic reticulum aminopeptidase 1
      and cytosolic proteases.
AB  - Although multiple components of the class I MHC processing pathway have been
      elucidated, the participation of nonproteasomal cytosolic enzymes has been
      largely unexplored. In this study, we provide evidence for multiple cytosolic
      mechanisms in the generation of an HLA-A*0201-associated epitope from tyrosinase.
      This epitope is presented in two isoforms containing either Asn or Asp, depending
      on the structure of the tyrosinase precursor. We show that deamidation of Asn to
      Asp is dependent on glycosylation in the endoplasmic reticulum (ER), and
      subsequent deglycosylation by peptide-N-glycanase in the cytosol. Epitope
      precursors with N-terminal extensions undergo a similar process. This is linked
      to an inability of ER aminopeptidase 1 to efficiently remove N-terminal residues,
      necessitating processing by nonproteasomal peptidases in the cytosol. Our work
      demonstrates that processing of this tyrosinase epitope involves recycling
      between the ER and cytosol, and an obligatory interplay between enzymes involved
      in proteolysis and glycosylation/deglycosylation located in both compartments.

PMID- 17015731
TI  - CDw78 defines MHC class II-peptide complexes that require Ii chain-dependent
      lysosomal trafficking, not localization to a specific tetraspanin membrane
      microdomain.
AB  - MHC class II molecules (MHC-II) associate with detergent-resistant membrane
      microdomains, termed lipid rafts, which affects the function of these molecules
      during Ag presentation to CD4+ T cells. Recently, it has been proposed that MHC
      II also associates with another type of membrane microdomain, termed tetraspan
      microdomains. These microdomains are defined by association of molecules to a
      family of proteins that contain four-transmembrane regions, called tetraspanins.
      It has been suggested that MHC-II associated with tetraspanins are selectively
      identified by a mAb to a MHC-II determinant, CDw78. In this report, we have re
      examined this issue of CDw78 expression and MHC-II-association with tetraspanins
      in human dendritic cells, a variety of human B cell lines, and MHC-II-expressing
      HeLa cells. We find no correlation between the expression of CDw78 and the
      expression of tetraspanins CD81, CD82, CD53, CD9, and CD37. Furthermore, we find
      that the relative amount of tetraspanins bound to CDw78-reactive MHC-II is
      indistinguishable from the amount bound to peptide-loaded MHC-II. We found that
      expression of CDw78 required coexpression of MHC-II together with its chaperone
      Ii chain. In addition, analysis of a panel of MHC-II-expressing B cell lines
      revealed that different alleles of HLA-DR express different amounts of CDw78
      reactivity. We conclude that CDw78 defines a conformation of MHC-II bound to
      peptides that are acquired through trafficking to lysosomal Ag-processing
      compartments and not MHC-II-associated with tetraspanins.

PMID- 17015732
TI  - Antibody repertoire development in fetal and neonatal piglets. XIII. Hybrid VH
      genes and the preimmune repertoire revisited.
AB  - The expressed porcine VH genes belong to the VH3 family (clan), four of which,
      VHA, VHB, VHC, and VHE, alone comprise approximately 80% of the preimmune
      repertoire. However, so-called "hybrid" VH genes that use CDR1 of one VH gene and
      the CDR2 of another are frequently encountered. We studied > 3000 cloned VDJs and
      found that such hybrids can contribute up to 10% of the preimmune repertoire.
      Based on the 1) recovery of hybrid VH genes from bacterial artificial chromosome
      clones, 2) frequency of occurrence of certain hybrids in the preimmune
      repertoire, and 3) failure to recover equal numbers of reciprocal hybrids, we
      concluded that some chimeric genes are present in the genome and are not PCR
      artifacts. Two chimeric germline genes (VHZ and VHY), together with VHF and the
      four genes mentioned above, constitute the major VH genes and these account for >
      95% of the preimmune repertoire. Diversification of the preimmune IgG and IgM
      repertoires after environmental exposure was mainly due to somatic hypermutation
      of major VH genes with no evidence of gene conversion. Somatic hypermutation was
      3- to 10-fold higher in CDRs than in framework regions, most were R mutations and
      transversions and transitions equally contributed. Data were used to 1) develop
      an index to quantify the degree of VH repertoire diversification and 2) establish
      a library of 29 putative porcine VH genes. One-third of these genes are chimeric
      genes and their sequences suggest that the porcine VH genome developed by
      duplication and splicing from a small number of prototypic genes.

PMID- 17015733
TI  - Lectin pathway of bony fish complement: identification of two homologs of the
      mannose-binding lectin associated with MASP2 in the common carp (Cyprinus
      carpio).
AB  - The lectin pathway of complement is considered to be the most ancient complement
      pathway as inferred from identification of ancient homologs of mannose-binding
      lectin (MBL) and MBL-associated serine proteases (MASPs) in some invertebrates.
      MBL homologs with galactose selectivity and an MASP3-like sequence also occur in
      bony fish, linking the evolution of the lectin complement pathway from
      invertebrates to higher vertebrates. However, these cannot be considered
      authentic complement components until confirmatory functional evidence is
      obtained. Here, we report the isolation and characterization of two MBL homologs
      from a cyprinid teleost, the common carp, Cyprinus carpio. One, designated GalBL,
      corresponds to the MBL-like molecule with the galactose specificity. The other is
      an authentic MBL with mannose specificity. Both were found to associate with a
      serine protease that cleaves native human C4 into C4b but not C4i with a
      hydrolyzed thioester. Molecular cloning and phylogenetic analysis revealed this
      C4-activating protease to be carp MASP2, indicating that MASP2 arose before the
      emergence of bony fish. Database mining of MBL-like genes reveals that MBL and
      GalBL genes are arranged in tandem in the zebrafish genome and that both lectins
      are conserved in the distantly related puffer fish. These results imply that bony
      fish have developed a diverged set of MBL homologs that function in the lectin
      complement pathway.

PMID- 17015734
TI  - Antibody repertoire development in fetal and neonatal piglets. XVII. IgG subclass
      transcription revisited with emphasis on new IgG3.
AB  - Fetal piglets offer an in vivo model for determining whether Ag-independent IgG
      subclass transcription proceeds in a manner that differs from subclass
      transcription in pigs exposed to environmental Ags and TLR ligands. Our data from
      approximately 12,000 Cgamma clones from > 60 piglets provide the first report on
      the relative usage of all known porcine Cgamma genes in fetal and young pigs.
      Studies revealed that among the six Cgamma genes, allelic variants of IgG1
      comprised 50-80% of the repertoire, and IgG2 alleles comprised < 10% in nearly
      all tissues. However, relative transcription of allelic variants of IgG1 randomly
      deviate from the 1:1 ratio expected in heterozygotes. Most surprising was the
      finding that IgG3 accounted for half of all Cgamma transcripts in the ileal
      Peyer's patches (IPPs) and mesenteric lymph nodes but on average only
      approximately 5% of the clones from the thymus, tonsil, spleen, peripheral blood,
      and bone marrow of newborns. Lymphoid tissues from late term fetuses revealed a
      similar expression pattern. Except for IgG3 in the IPPs and mesenteric lymph
      nodes, no stochastic pattern of Cgamma expression during development was seen in
      animals from mid-gestation through 5 mo. The age and tissue dependence of IgG3
      transcription paralleled the developmental persistence of the IPP, and its near
      disappearance corresponds to the diversification of the preimmune VDJ repertoire
      in young piglets. We hypothesize that long-hinged porcine IgG3 may be important
      in preadaptive responses to T cell-independent Ags similar to those described for
      its murine namesake.

PMID- 17015735
TI  - Increased human IgE induced by killing Schistosoma mansoni in vivo is associated
      with pretreatment Th2 cytokine responsiveness to worm antigens.
AB  - In schistosomiasis endemic areas, children are very susceptible to
      postchemotherapy reinfection, whereas adults are relatively resistant. Different
      studies have reported that schistosome-specific IL-4 and IL-5 responses, or
      posttreatment worm-IgE levels, correlate with subsequent low reinfection.
      Chemotherapy kills i.v. worms providing an in vivo Ag challenge. We measured anti
      worm (soluble worm Ag (SWA) and recombinant tegumental Ag (rSm22.6)) and anti-egg
      (soluble egg Ag) Ab levels in 177 Ugandans (aged 7-50) in a high Schistosoma
      mansoni transmission area, both before and 7 wk posttreatment, and analyzed these
      data in relation to whole blood in vitro cytokine responses at the same time
      points. Soluble egg Ag-Ig levels were unaffected by treatment but worm-IgG1 and 
      IgG4 increased, whereas worm-IgE increased in many but not all individuals. An
      increase in worm-IgE was mainly seen in >15-year-olds and, unlike in children,
      was inversely correlated to pretreatment infection intensities, suggesting this
      response was associated both with resistance to pretreatment infection, as well
      as posttreatment reinfection. The increases in SWA-IgE and rSm22.6-IgE positively
      correlated with pretreatment Th2 cytokines, but not IFN-gamma, induced by SWA.
      These relationships remained significant after allowing for the confounding
      effects of pretreatment infection intensity, age, and pretreatment IgE levels,
      indicating a link between SWA-specific Th2 cytokine responsiveness and subsequent
      increases in worm-IgE. An exceptionally strong relationship between IL-5 and
      posttreatment worm-IgE levels in < 15-year-olds suggested that the failure of
      younger children to respond to in vivo Ag stimulation with increased levels of
      IgE, is related to their lack of pretreatment SWA Th2 cytokine responsiveness.

PMID- 17015736
TI  - Critical role of prostaglandin E2 overproduction in impaired pulmonary host
      response following bone marrow transplantation.
AB  - The success of bone marrow transplantation (BMT) as a therapy for malignant and
      inherited disorders is limited by infectious complications. We previously
      demonstrated syngeneic BMT mice are more susceptible to Pseudomonas aeruginosa
      pneumonia due to defects in the ability of donor-derived alveolar macrophages
      (AMs), but not polymorphonuclear leukocytes (PMNs), to phagocytose bacteria. We
      now demonstrate that both donor-derived AMs and PMNs display bacterial killing
      defects post-BMT. PGE2 is a lipid mediator with potent immunosuppressive effects
      against antimicrobial functions. We hypothesize that enhanced PGE2 production
      post-BMT impairs host defense. We demonstrate that lung homogenates from BMT mice
      contain 2.8-fold more PGE2 than control mice, and alveolar epithelial cells (2.7
      fold), AMs (125-fold), and PMNs (10-fold) from BMT animals all overproduce PGE2.
      AMs also produce increased prostacyclin (PGI2) post-BMT. Interestingly, the E
      prostanoid (EP) receptors EP2 and EP4 are elevated on donor-derived phagocytes
      post-BMT. Blocking PGE2 synthesis with indomethacin overcame the phagocytic and
      killing defects of BMT AMs and the killing defects of BMT PMNs in vitro. The
      effect of indomethacin on AM phagocytosis could be mimicked by an EP2 antagonist,
      AH-6809, and exogenous addition of PGE2 reversed the beneficial effects of
      indomethacin in vitro. Importantly, in vivo treatment with indomethacin reduced
      PGE2 levels in lung homogenates and restored in vivo bacterial clearance from the
      lung and blood in BMT mice. Genetic reduction of cyclooxygenase-2 in BMT mice
      also had similar effects. These data clearly demonstrate that overproduction of
      PGE2 post-BMT is a critical factor determining impaired host defense against
      pathogens.

PMID- 17015737
TI  - In the absence of reactive oxygen species, T cells default to a Th1 phenotype and
      mediate protection against pulmonary Cryptococcus neoformans infection.
AB  - In recent years, the prevalence of invasive fungal infections has increased,
      attributed mostly to the rising population of immunocompromised individuals.
      Cryptococcus neoformans has been one of the most devastating, with an estimated 6
      8% of AIDS-infected patients succumbing to Cryptococcus-associated meningitis.
      Reactive oxygen species (ROS) are potent antimicrobial agents but also play a
      significant role in regulating immune cell phenotype, but cause immunopathology
      when produced in excess. We now show that mice lacking phagocyte NADPH oxidase
      have heightened macrophage and Th1 responses and improved pathogen containment
      within pulmonary granulomatous lesions. Consequently, dissemination of this
      fungus to the brain is diminished, an effect that is independent of IL-12.
      Similar results are described using the metalloporphyrin antioxidant
      manganese(III) tetrakis(N-ethyl pyridinium-2-yl)porphyrin, which also promoted a
      protective Th1 response and reduced dissemination to the brain. These findings
      are in sharp contrast to the protective potential of ROS against other fungal
      pathogens, and highlight the pivotal role that ROS can fulfill in shaping the
      profile of the host's immune response.

PMID- 17015738
TI  - Mannose-binding lectin augments the uptake of lipid A, Staphylococcus aureus, and
      Escherichia coli by Kupffer cells through increased cell surface expression of
      scavenger receptor A.
AB  - We investigated roles of scavenger receptor A (SR-A) and mannose-binding lectin
      (MBL) in the uptake of endotoxin and bacteria by Kupffer cells. When [3H]lipid A
      was injected into retro-orbital plexus of mice, significantly less accumulation
      of lipid A in the liver was observed in SR-A-deficient mice and wild-type mice
      coinjected with fucoidan or acetylated low-density lipoprotein, which are known
      ligands for SR-A. Isolated Kupffer cells were able to take up [3H]lipid A in a
      time-dependent manner. The amount of lipid A associated with nonadherent Kupffer
      cells derived from SR-A-deficient mice was reduced by approximately 80% when
      compared with wild-type cells, indicating an important role of SR-A in endotoxin
      uptake by Kupffer cells. The lipid A uptake by Kupffer cells was significantly
      enhanced in the presence of rMBL. Coincubation of fucoidan with [3H]lipid A
      significantly inhibited the basal and the MBL-stimulated uptake of lipid A by
      Kupffer cells. Preincubation of MBL with Kupffer cells also increased the uptake
      of lipid A. These results indicate that MBL augments the SR-A-mediated uptake of
      lipid A by Kupffer cells. Consistently, the exposure of MBL to Kupffer cells
      increased cell surface SR-A expression. The phagocytosis of Staphylococcus aureus
      and Escherichia coli by Kupffer cells was also enhanced by preincubation of MBL
      with the cells. In addition, MBL bound to lipid A, LPS, and S. aureus, and
      precipitated S. aureus. This study demonstrates important roles of SR-A and MBL
      in the uptake of endotoxin and bacteria by Kupffer cells.

PMID- 17015739
TI  - Mucosal vaccine targeting improves onset of mucosal and systemic immunity to
      botulinum neurotoxin A.
AB  - Absence of suitable mucosal adjuvants for humans prompted us to consider
      alternative vaccine designs for mucosal immunization. Because adenovirus is adept
      in binding to the respiratory epithelium, we tested the adenovirus 2 fiber
      protein (Ad2F) as a potential vaccine-targeting molecule to mediate vaccine
      uptake. The vaccine component (the host cell-binding domain to botulinum toxin
      (BoNT) serotype A) was genetically fused to Ad2F to enable epithelial binding.
      The binding domain for BoNT was selected because it lies within the
      immunodominant H chain as a beta-trefoil (Hcbetatre) structure; we hypothesize
      that induced neutralizing Abs should be protective. Mice were nasally immunized
      with the Hcbetatre or Hcbetatre-Ad2F, with or without cholera toxin (CT). Without
      CT, mice immunized with Hcbetatre produced weak secretory IgA (sIgA) and plasma
      IgG Ab response. Hcbetatre-Ad2F-immunized mice produced a sIgA response
      equivalent to mice coimmunized with CT. With CT, Hcbetatre-Ad2F-immunized mice
      showed a more rapid onset of sIgA and plasma IgG Ab responses that were supported
      by a mixed Th1/Th2 cells, as opposed to mostly Th2 cells by Hcbetatre-dosed mice.
      Mice immunized with adjuvanted Hcbetatre-Ad2F or Hcbetatre were protected against
      lethal BoNT serotype A challenge. Using a mouse neutralization assay, fecal Abs
      from Hcbetatre-Ad2F or Hcbetatre plus CT-dosed mice could confer protection.
      Parenteral immunization showed that the inclusion of Ad2F enhances anti-Hcbetatre
      Ab titers even in the absence of adjuvant. This study shows that the Hcbetatre
      structure can confer protective immunity and that use of Hcbetatre-Ad2F gives
      more rapid and sustained mucosal and plasma Ab responses.

PMID- 17015740
TI  - Release of LL-37 by activated human Vgamma9Vdelta2 T cells: a microbicidal weapon
      against Brucella suis.
AB  - Human Vgamma9Vdelta2 T cells play a crucial role in early immune response to
      intracellular pathogens. Moreover, in brucellosis, these cells are drastically
      increased in the peripheral blood of patients during the acute phase of
      infection. In vitro, Vgamma9Vdelta2 T cells are capable of inhibiting Brucella
      growth and development through a combination of mechanisms: 1) cytotoxicity, 2)
      macrophage activation and bactericidal activity through cytokine and chemokine
      secretion, and 3) antibacterial effects. We previously described that
      antibacterial factors were found in supernatants from activated Vgamma9Vdelta2 T
      cells. In this study, we show that Vgamma9Vdelta2 T cells express the human
      cathelicidin hCAP18 and its mature form, known as LL-37, is released upon
      activation of Vgamma9Vdelta2 T cells. We also show that LL-37 has an
      antibacterial effect on Brucella suis. Overall, our results demonstrate that LL
      37 is a soluble factor responsible for a part of the bactericidal activity of
      Vgamma9Vdelta2 T cells.

PMID- 17015741
TI  - Differential modulation of human lactoferrin activity against both R5 and X4-HIV
      1 adsorption on epithelial cells and dendritic cells by natural antibodies.
AB  - Human lactoferrin (Lf) is an iron binding glycoprotein that is present in several
      mucosal secretions. Many biological functions have been ascribed to Lf. In the
      present study, we showed that Lf limited specifically adsorption of R5- and X4
      HIV-1-free particles on endometrial epithelial HEC-1A cells, by inhibiting virus
      adsorption on heparan-sulfated proteoglycans. But, Lf did not interfere with both
      R5 and X4-HIV transcytosis. We showed also the efficacy of Lf in preventing R5
      and X4-HIV capture by dendritic cells. Conversely, we demonstrated that Lf
      reacting natural Abs (NAbs) present within i.v. Ig-enhanced HIV attachment on
      dendritic cells by forming HIV-Lf-NAbs. HIV particles were able to directly
      interact with Lf following its interaction with NAbs. We also found Lf-reacting
      natural Abs within cervicovaginal secretions, suggesting the existence of Lf-NAbs
      complexes in women genital tract in vivo. In conclusion, this study highlights Lf
      as a potent microbicides and reports new function for NAbs within the genital
      compartment that may compartment that may abolish the inhibitory activity of
      microbicide compounds. Thus, we proposed a model in which Lf would appear as a
      double-edged sword that could have beneficial or detrimental effects depending on
      both cellular and molecular environments. This study highlights the use of Lf
      derivates as microbicide candidates to limit such interferences.

PMID- 17015742
TI  - Involvement of the urokinase kringle domain in lipopolysaccharide-induced acute
      lung injury.
AB  - Urokinase plasminogen activator (uPA) plays a major role in fibrinolytic
      processes and also can potentiate LPS-induced neutrophil activation through
      interactions with its kringle domain (KD). To investigate the role of the uPA KD
      in modulating acute inflammatory processes in vivo, we cloned and then developed
      Abs to the murine uPA KD. Increased pulmonary expression of uPA and the uPA KD
      was present in the lungs after LPS exposure. Administration of anti-kringle Abs
      diminished LPS-induced up-regulation of uPA and uPA KD in the lungs, and also
      decreased the severity of LPS-induced acute lung injury, as determined by
      development of lung edema, pulmonary neutrophil accumulation, histology, and lung
      IL-6, MIP-2, and TNF-alpha cytokine levels. These proinflammatory effects of the
      uPA KD appeared to be mediated through activation of Akt and NF-kappaB. The
      present studies indicate that the uPA KD plays a major role in the development of
      TLR4-mediated acute inflammatory processes, including lung injury. Blockade of
      the uPA KD may prevent the development or ameliorate the severity of acute lung
      injury induced through TLR4-dependent mechanisms, such as would occur in the
      setting of Gram-negative pulmonary or systemic infection.

PMID- 17015743
TI  - Retrovirus-mediated over-expression of decay-accelerating factor rescues Crry
      deficient erythrocytes from acute alternative pathway complement attack.
AB  - Decay-accelerating factor (DAF) and complement receptor 1-related gene/protein y
      (Crry) are two membrane-bound complement regulators on murine erythrocytes that
      inhibit C3/C5 convertases. Previously, we found that Crry- but not DAF-deficient
      erythrocytes were susceptible to alternative pathway complement-mediated
      elimination in vivo. To determine whether it is a unique activity or a higher
      level expression of Crry makes it indispensable on murine erythrocytes, we over
      expressed DAF on Crry-deficient (Crry(-/-)) erythrocytes by retroviral vector
      mediated DAF gene transduction of bone marrow stem cells. DAF retrovirus
      transduced erythrocytes expressed 846 +/- 127 DAF molecules/cell (DAF(high))
      compared with 249 +/- 94 DAF molecules/cell (DAF(low)) and 774 +/- 135 Crry
      molecules/cell on control mouse erythrocytes. DAF(high)-Crry(-/-) erythrocytes
      were significantly more resistant than either DAF(low)-Crry(-/-), DAF(-/-) 
      Crry(+/+) or wild-type erythrocytes to classical pathway complement-mediated C3
      deposition in vitro. Furthermore, increased DAF expression rescued Crry(-/-)
      erythrocytes from acute alternative pathway complement attack in vivo. Notably,
      long term monitoring revealed that DAF(high)-Crry(-/-) erythrocytes were still
      more susceptible than wild-type erythrocytes to complement-mediated elimination
      as they had a shorter half-life in complement-sufficient mice but survived
      equally well in complement-deficient mice. These results suggest that both a high
      level expression and a more potent anti-alternative pathway complement activity
      of Crry contributed to its indispensable role on murine erythrocytes.
      Additionally, they demonstrate the feasibility of using stem cell gene therapy to
      correct membrane complement regulator deficiency on blood cells in vivo.

PMID- 17015744
TI  - Membrane-bound CC chemokine inhibitor 35K provides localized inhibition of CC
      chemokine activity in vitro and in vivo.
AB  - CC chemokines mediate mononuclear cell recruitment and activation in chronic
      inflammation. We have shown previously that gene transfer using recombinant
      adenoviruses, encoding a soluble CC chemokine-binding protein of vaccinia virus
      35K, can dramatically reduce atherosclerosis and vein graft remodeling in
      apolipoprotein E knockout mice. In this study, we report the development of a
      membrane-bound form of 35K (m35K), tagged with GFP, which allows for localized,
      broad-spectrum CC chemokine blockade. In vitro experiments indicate that m35K
      expressing cells no longer undergo CC chemokine-induced chemotaxis, and m35K
      expressing cells can locally deplete the CC chemokines RANTES (CCL5) and MIP
      1alpha (CCL3) from supernatant medium. This sequestration of CC chemokines can
      prevent chemotaxis of bystander cells to CC, but not CX(3)C chemokines.
      Intraperitoneal injection of mice with an adenovirus-encoding m35K leads to a
      significant (44%) decrease in leukocyte recruitment into the peritoneal cavity in
      a sterile peritonitis model. Intravenous adenovirus-encoding m35K delivery leads
      to m35K expression in hepatocytes, which confers significant protection against
      liver damage (75% reduction in liver enzymes) in a Con A-induced hepatitis model.
      In summary, we have generated a membrane-bound CC chemokine-binding protein
      (m35K) that provides localized broad-spectrum CC chemokine inhibition in vitro
      and in vivo. m35K may be a useful tool to study the role of CC chemokines in
      leukocyte trafficking and block the recruitment of monocytes in chronic
      inflammation.

PMID- 17015745
TI  - IL-1beta regulates blood-brain barrier permeability via reactivation of the
      hypoxia-angiogenesis program.
AB  - Loss of blood-brain barrier (BBB) integrity is believed to be an early and
      significant event in lesion pathogenesis in the inflammatory demyelinating
      disease multiple sclerosis (MS), and understanding mechanisms involved may lead
      to novel therapeutic avenues for this disorder. Well-differentiated endothelium
      forms the basis of the BBB, while astrocytes control the balance between barrier
      stability and permeability via production of factors that restrict or promote
      vessel plasticity. In this study, we report that the proinflammatory cytokine IL
      1beta, which is prominently expressed in active MS lesions, causes a shift in the
      expression of these factors to favor plasticity and permeability. The
      transcription factor, hypoxia inducible factor-1 (HIF-1), plays a significant
      role in this switch. Using a microarray-based approach, we found that in human
      astrocytes, IL-1beta induced the expression of genes favoring vessel plasticity,
      including HIF-1alpha and its target, vascular endothelial growth factor-A (VEGF
      A). Demonstrating relevance to MS, we showed that HIF-1alpha and VEGF-A were
      expressed by reactive astrocytes in active MS lesions, while the VEGF receptor
      VEGFR2/flk-1 localized to endothelium and IL-1 to microglia/macrophages.
      Suggesting functional significance, we found that expression of IL-1beta in the
      brain induced astrocytic expression of HIF-1alpha, VEGF-A, and BBB permeability.
      In addition, we confirmed VEGF-A to be a potent inducer of BBB permeability and
      angiogenesis, and demonstrated the importance of IL-1beta-induced HIF-1alpha in
      its regulation. These results suggest that IL-1beta contributes to BBB
      permeability in MS via reactivation of the HIF-VEGF axis. This pathway may
      represent a potential therapeutic target to restrict lesion formation.

PMID- 17015746
TI  - Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial
      hyperplasia and angiogenesis.
AB  - Serum amyloid A (SAA) is a major acute-phase reactant, and has been demonstrated
      to mediate proinflammatory cellular responses. Although SAA has been used as an
      indicator for a variety of inflammatory diseases, the role of SAA in synovial
      hyperplasia and proliferation of endothelial cells, a pathological hallmark of
      rheumatoid arthritis (RA), has yet to be elucidated. In this study, we have
      demonstrated that SAA promotes the proliferation of human fibroblast-like
      synoviocytes (FLS). In addition, SAA protects RA FLS against the apoptotic death
      induced by serum starvation, anti-Fas IgM, and sodium nitroprusside. The activity
      of SAA appears to be mediated by the formyl peptide receptor-like 1 (FPRL1)
      receptor, as it was mimicked by the WKYMVm peptide, a specific ligand for FPRL1,
      but completely abrogated by down-regulating the FPRL1 transcripts with short
      interfering RNA. The effect of SAA on FLS hyperplasia was shown to be caused by
      an increase in the levels of intracellular calcium, as well as the activation of
      ERK and Akt, which resulted in an elevation in the expression of cyclin D1 and
      Bcl-2. Moreover, SAA stimulated the proliferation, migration, and tube formation
      of endothelial cells in vitro, and enhanced the sprouting activity of endothelial
      cells ex vivo and neovascularization in vivo. These observations indicate that
      the binding of SAA to FPRL1 may contribute to the destruction of bone and
      cartilage via the promotion of synoviocyte hyperplasia and angiogenesis, thus
      providing a potential target for the control of RA.

PMID- 17015747
TI  - Inhibition of arginase I activity by RNA interference attenuates IL-13-induced
      airways hyperresponsiveness.
AB  - Increased arginase I activity is associated with allergic disorders such as
      asthma. How arginase I contributes to and is regulated by allergic inflammatory
      processes remains unknown. CD4+ Th2 lymphocytes (Th2 cells) and IL-13 are two
      crucial immune regulators that use STAT6-dependent pathways to induce allergic
      airways inflammation and enhanced airways responsiveness to spasmogens (airways
      hyperresponsiveness (AHR)). This pathway is also used to activate arginase I in
      isolated cells and in hepatic infection with helminths. In the present study, we
      show that arginase I expression is also regulated in the lung in a STAT6
      dependent manner by Th2-induced allergic inflammation or by IL-13 alone. IL-13
      induced expression of arginase I correlated directly with increased synthesis of
      urea and with reduced synthesis of NO. Expression of arginase I, but not
      eosinophilia or mucus hypersecretion, temporally correlated with the development,
      persistence, and resolution of IL-13-induced AHR. Pharmacological supplementation
      with l-arginine or with NO donors amplified or attenuated IL-13-induced AHR,
      respectively. Moreover, inducing loss of function of arginase I specifically in
      the lung by using RNA interference abrogated the development of IL-13-induced
      AHR. These data suggest an important role for metabolism of l-arginine by
      arginase I in the modulation of IL-13-induced AHR and identify a potential
      pathway distal to cytokine receptor interactions for the control of IL-13
      mediated bronchoconstriction in asthma.

PMID- 17015748
TI  - Differential pattern of inflammatory molecule regulation in intestinal epithelial
      cells stimulated with IL-1.
AB  - To better predict the consequences of blocking signal transduction pathways as a
      means of controlling intestinal inflammation, we are characterizing the pathways
      up-regulated by IL-1 in intestinal epithelial cells (IEC). IL-1beta induced
      increased mRNA levels of MIP-2, MCP-1, RANTES, inducible NO synthase (iNOS), and
      cyclooxygenase-2 (COX-2) in the IEC-18 cell line. IL-1beta activated NF-kappaB
      but not ERK or p38. Infecting cells with adenovirus expressing a mutated gene for
      IkappaBalpha (IkappaBAA) blocked IL-1-induced mRNA increases in MIP-2, MCP-1, and
      iNOS but not COX-2 or RANTES. Expression of IkappaBAA attenuated the IL-1-induced
      increase in COX-2 protein. Unexpectedly, RANTES mRNA increased, and protein was
      secreted by cells expressing IkappaBAA in the absence of IL-1. Adenovirus
      expressing IkappaBAA, blocking protein synthesis, and IL-1beta all resulted in
      activation of JNK. The JNK inhibitor SP600125 prevented the RANTES increases by
      all three stimuli. A human enterocyte line was similarly examined, and both NF
      kappaB and JNK regulate IL-1-induced RANTES secretion. We conclude that in IEC
      18, IL-1beta-induced increases in mRNA for MIP-2, MCP-1, and iNOS are NF-kappaB
      dependent, whereas regulation of RANTES mRNA is independent of NF-kappaB but is
      positively regulated by JNK. IL-1beta-induced mRNA increases in COX-2 mRNA are
      both NF-kappaB- and MAPK-independent but the translation of COX-2 protein is NF
      kappaB-dependent. This pattern of signaling due to a single stimulus exposed the
      complexities of regulating inflammatory genes in IEC.

PMID- 17015749
TI  - Deguelin, an Akt inhibitor, suppresses IkappaBalpha kinase activation leading to
      suppression of NF-kappaB-regulated gene expression, potentiation of apoptosis,
      and inhibition of cellular invasion.
AB  - Deguelin, a constituent of the bark of the African plant Mundulea sericea
      (Leguminosae), exhibits antiproliferative and anticarcinogenic activities through
      a mechanism that is not well understood. Because various steps in carcinogenesis
      are regulated by NF-kappaB, we postulated that the activity of deguelin is
      mediated through this transcription factor. We found that deguelin suppressed NF
      kappaB activation induced by carcinogens, tumor promoters, growth factors, and
      inflammatory stimuli. This suppression was not cell-type specific, because NF
      kappaB activation was suppressed in both lymphoid and epithelial cells. Moreover,
      constitutive NF-kappaB activation was also blocked by deguelin. The suppression
      of TNF-induced NF-kappaB activation by deguelin occurred through the inhibition
      of the activation of IkappaBalpha kinase, leading to sequential suppression of
      IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65
      nuclear translocation, and NF-kappaB-dependent reporter gene expression. Deguelin
      also suppressed the NF-kappaB reporter activity induced by TNFR1, TNFR-associated
      death domain, TNFR-associated factor 2, and IkappaBalpha kinase, but not that
      induced by p65. The inhibition of NF-kappaB activation thereby led to the down
      regulation of gene products involved in cell survival, proliferation, and
      invasion. Suppression of these gene products by deguelin enhanced the apoptosis
      induced by TNF and chemotherapeutic agents and suppressed TNF-induced cellular
      invasion. Our results demonstrate that deguelin inhibits the NF-kappaB activation
      pathway, which may explain its role in the suppression of carcinogenesis and
      cellular proliferation.

PMID- 17015750
TI  - Type I IFN modulates host defense and late hyperinflammation in septic
      peritonitis.
AB  - TLRs are considered important for the control of immune responses during
      endotoxic shock or polymicrobial sepsis. Signaling by TLRs may proceed through
      the adapter proteins MyD88 or TIR domain-containing adaptor inducinng IFN-beta.
      Both pathways can lead to the production of type I IFNs (IFN-alphabeta). In the
      present study, the role of the type I IFN pathway for host defense and immune
      pathology in sepsis was investigated using a model of mixed bacterial
      peritonitis. Systemic levels of IFN-alphabeta protein were markedly elevated
      during septic peritonitis. More detailed analyses revealed production of IFN
      beta, but not IFN-alpha subtypes, and identified CD11b+ CD11c- macrophage-like
      cells as major producers of IFN-beta. The results further demonstrate that in IFN
      alphabeta receptor I chain (IFNARI)-deficient mice, the early recruitment of
      neutrophils to the infected peritoneal cavity was augmented, most likely due to
      an increased local production of MCP-1 and leukotriene B4. In the absence of
      IFNARI, peritoneal neutrophils also exhibited enhanced production of reactive
      oxygen intermediates and elevated expression of Mac-1. Conversely, administration
      of recombinant IFN-beta resulted in reduced leukotriene B4 levels and decreased
      peritoneal neutrophil recruitment and activation. Analysis of the cytokine
      response to septic peritonitis revealed that IFNARI deficiency strongly
      attenuated late, but not early, hyperinflammation. In accordance with these
      findings, bacterial clearance and overall survival of IFNARI(-/-) mice were
      improved. Therefore, the present study reveals critical functions of the type I
      IFN pathway during severe mixed bacterial infections leading to sepsis. The
      results suggest that type I IFN exerts predominantly adverse effects under these
      conditions.

PMID- 17015751
TI  - Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory
      T cells through CTLA-4 signaling.
AB  - T cell-mediated autoimmunity to collagen V (col-V), a sequestered yet immunogenic
      self-protein, can induce chronic lung allograft rejection in rodent models. In
      this study we characterized the role of CD4+ CD25+ regulatory T cells (Tregs) in
      regulating col-V autoimmunity in human lung transplant (LT) recipients. LT
      recipients revealed a high frequency of col-V-reactive, IL-10-producing CD4+ T
      cells (T IL-10 cells) with low IL-2-, IFN-gamma-, IL-5-, and no IL-4-producing T
      cells. These T(IL-10) cells were distinct from Tregs because they lacked
      constitutive expression of both CD25 and Foxp3. Expansion of T IL-10 cells during
      col-V stimulation in vitro involved CTLA-4 on Tregs, because both depleting and
      blocking Tregs with anti-CTLA4 F(ab')2 mAbs resulted in loss of T IL-10 cells
      with a concomitant increase in IFN-gamma producing Th1 cells (TIFN-gamma cells).
      A Transwell culture of col-V-specific T IL-10 cells with Th1 cells (those
      generated in absence of Tregs) from the same patient resulted in marked
      inhibition of IFN-gamma and proliferation of T(IFN-gamma) cells, which was
      reversed by neutralizing IL-10. Furthermore, the T IL-10 cells were HLA class II
      restricted because blocking HLA class II on APCs resulted in the loss of IL-10
      production. Chronic lung allograft rejection was associated with the loss of
      Tregs with a concomitant decrease in T IL-10 cells and an increase in T IFN-gamma
      cells. We conclude that LT patients have col-V-specific T cells that can be
      detected in the peripheral blood. The predominant col-V-specific T cells produce
      IL-10 that suppresses autoreactive Th1 cells independently of direct cellular
      contact. Tregs are pivotal for the induction of these "suppressor" T IL-10 cells.

PMID- 17015752
TI  - Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive
      molecule IDO through RNA interference.
AB  - Tumor-derived immune suppression is a major impediment to successful immune/gene
      cancer therapy. In the present study, we describe a novel strategy to disrupt
      tumor-derived immune suppression by silencing a tolerogenic molecule of tumor
      origin, IDO, using small interfering RNA (siRNA). Silencing of IDO in B16F10
      cells in vitro using IDO-siRNA prevented catabolism of tryptophan and inhibited
      apoptosis of T cells. IDO-siRNA treatment of B16F10 cells in vitro inhibited
      subsequent growth, tumor formation, and the size of tumor formed, by those cells
      when transplanted into host mice. In vivo treatment of B16F10 tumor-bearing mice
      successfully postponed tumor formation time and significantly decreased tumor
      size. Furthermore, in vivo IDO-siRNA treatment resulted in recovery of T cells
      responses and enhancement of tumor-specific killing. Thus, silencing IDO may
      break tumor-derived immune suppression. These data indicate that RNA interference
      has potential to enhance cancer therapy by reinstalling anticancer immunity.

PMID- 17015753
TI  - Bacillus Calmette Guerin vaccination of human newborns induces a specific,
      functional CD8+ T cell response.
AB  - Mounting evidence points to CD8+ T cells playing an important role in protective
      immunity against Mycobacterium tuberculosis. The only available vaccine against
      tuberculosis, bacillus Calmette Guerin (BCG), has traditionally been viewed not
      to induce these cells optimally. In this study, we show that vaccination of human
      newborns with BCG does indeed induce a specific CD8+ T cell response. These cells
      degranulated or secreted IFN-gamma, but not both, when infant blood was incubated
      with BCG. This stimulation also resulted in proliferation and up-regulation of
      cytotoxic molecules. Overall, the specific CD8+ T cell response was
      quantitatively smaller than the BCG-induced CD4+ T cell response. Incubation of
      whole blood with M. tuberculosis also caused CD8+ T cell IFN-gamma expression. We
      conclude that BCG induces a robust CD8+ T cell response, which may contribute to
      vaccination-induced protection against tuberculosis.

PMID- 17015754
TI  - Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive
      autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis.
AB  - Our previous results revealed that Igs in lesions and single chain variable
      fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid
      (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To
      study the axonal Ags involved in MS, we identified the glycolytic enzymes,
      triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs
      generated from clonal B cells in the CSF and in lesions from MS patients.
      Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%),
      clinically isolated syndrome (CIS) suggestive of MS (40%), other inflammatory
      neurological diseases (OIND; 29%), and other noninflammatory neurological
      diseases (ONIND; 31%). Levels of GAPDH-reactive Abs were elevated in MS patients
      (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%). The coexistence of
      both autoantibodies was detected in 10 MS patients (29%), and 1 CIS patient (3%),
      but not in patients with OIND/ONIND. Two scFv-Abs generated from the CSF and from
      lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively. The
      findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune
      response to neurons and axons in MS.

PMID- 17015755
TI  - Differential expression of CD11c by peripheral blood NK cells reflects temporal
      activity of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease, showing a great degree of
      variance in temporal disease activity. We have recently demonstrated that
      peripheral blood NK cells biased for secreting IL-5 (NK2 bias) are associated
      with the remission state of MS. In this study, we report that MS patients in
      remission differentially express CD11c on NK cell surface (operationally defined
      as CD11chigh or CD11clow). When we compared CD11chigh or CD11clow patients, the
      expression of IL-5 and GATA-3 in NK cells supposed to endow a disease-protective
      NK2 phenotype was observed in CD11clow but not in CD11chigh patients. In
      contrast, the CD11chigh group showed a higher expression of HLA-DR on NK cells.
      In vitro studies demonstrated that NK cell stimulatory cytokines such as IL-15
      would up-regulate CD11c expression on NK cells. Given previous evidence showing
      an association between an increased level of proinflammatory cytokines and
      temporal disease activity in MS, we postulate that inflammatory signals may play
      a role in inducing the CD11chigh NK cell phenotype. Follow-up of a new cohort of
      patients showed that 6 of 10 CD11chigh MS patients developed a clinical relapse
      within 120 days after evaluation, whereas only 2 of 13 CD11clow developed
      exacerbated disease (p = 0.003). As such, a higher expression of CD11c on NK
      cells may reflect the temporal activity of MS as well as a loss of regulatory NK2
      phenotype, which may allow us to use it as a potential biomarker to monitor the
      immunological status of MS patients.

PMID- 17015756
TI  - Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of
      MHC class II restriction by an antibody-like immunoreceptor.
AB  - Immune elimination of tumor cells requires the close cooperation between CD8+ CTL
      and CD4+ Th cells. We circumvent MHC class II-restriction of CD4+ T cells by
      expression of a recombinant immunoreceptor with an Ab-derived binding domain
      redirecting specificity. Human CD4+ T cells grafted with an immunoreceptor
      specific for carcinoembryonic Ag (CEA) are activated to proliferate and secrete
      cytokines upon binding to CEA+ target cells. Notably, redirected CD4+ T cells
      mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected
      CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but
      mediated by perforin and granzyme because cytolysis is inhibited by blocking the
      release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha.
      CD4+ T cells redirected by Ab-derived immunoreceptors in a MHC class II
      independent fashion substantially extend the power of an adoptive, Ag-triggered
      immunotherapy not only by CD4+ T cell help, but also by cytolytic effector
      functions. Because cytolysis is predominantly mediated via granzyme/perforin,
      target cells that are resistant to death receptor signaling become sensitive to a
      cytolytic attack by engineered CD4+ T cells.

PMID- 17015757
TI  - Development of autoimmunity in IL-14alpha-transgenic mice.
AB  - Multiple genetic loci contribute to the development of systemic lupus
      erythematosus (SLE). In murine models for SLE, various genes on chromosome four
      have been implicated. IL-14 is a cytokine originally identified as a B cell
      growth factor. The il14 gene is located on chromosome 4. IL-14alpha is a cytokine
      encoded by the plus strand of the IL-14 gene using exons 3-10. The expression of
      IL-14alpha is increased in (NZB x NZW)F1 mice. In this study, we produced IL
      14alpha-transgenic mice to study the role of IL-14alpha in the development of
      autoimmunity. At age 3-9 mo, IL-14alpha-transgenic mice demonstrate increased
      numbers of B1 cells in the peritoneum, increased serum IgM, IgG, and IgG 2a and
      show enhanced responses to T-dependent and T-independent Ags compared with
      littermate controls. At age 9-17 mo, IL-14alpha-transgenic mice develop
      autoantibodies, sialadenitis, as in Sjogren's syndrome, and immune complex
      mediated nephritis, as in World Health Organization class II SLE nephritis.
      Between the ages 14-18 mo, 95% of IL-14alpha-transgenic mice developed CD5+ B
      cell lymphomas, consistent with the lymphomas seen in elderly patients with
      Sjogren's syndrome and SLE. These data support a role for IL-14alpha in the
      development of both autoimmunity and lymphomagenesis. These studies may provide a
      genetic link between these often related disorders.

PMID- 17015759
TI  - Vector prime/protein boost vaccine that overcomes defects acquired during aging
      and cancer.
AB  - We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune
      response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the
      Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags.
      When the TAA/ecdCD40L protein is given s.c. as a boost following the Ad-sig
      TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase
      dramatically over that seen with vector alone, in young (2-mo-old) as well as old
      (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer.
      This vaccine also induces a 4-fold decrement of negative regulatory CD4CD25FOXP3
      T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad
      sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be
      valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms.

PMID- 17015758
TI  - Macrophage migration inhibitory factor deficiency attenuates macrophage
      recruitment, glomerulonephritis, and lethality in MRL/lpr mice.
AB  - Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disease of
      unknown etiology. Macrophage migration inhibitory factor (MIF) is a
      proinflammatory cytokine that is operative in innate and adaptive immunity and
      important in immune-mediated diseases such as rheumatoid arthritis and
      atherosclerosis. The functional relevance of MIF in systemic autoimmune diseases
      such as SLE is unknown. Using the lupus-prone MRL/lpr mice, we aim to examine the
      expression and function of MIF in this murine model of systemic autoimmune
      disease. These experiments revealed that renal MIF expression was significantly
      higher in MRL/lpr mice compared with nondiseased control mice (MRL/MpJ), and MIF
      was also markedly up-regulated in skin lesions of MRL/lpr mice. To examine the
      effect of MIF on development of systemic autoimmune disease, we generated MRL/lpr
      mice with a targeted disruption of the MIF gene (MIF(-/-)MRL/lpr), and compared
      their disease manifestations to MIF(+/+)MRL/lpr littermates. MIF(-/-)MRL/lpr mice
      exhibited significantly prolonged survival, and reduced renal and skin
      manifestations of SLE. These effects occurred in the absence of major changes in
      T and B cell markers or alterations in autoantibody production. In contrast,
      renal macrophage recruitment and glomerular injury were significantly reduced in
      MIF(-/-)MRL/lpr mice, and this was associated with reduction in the monocyte
      chemokine MCP-1. Taken together, these data suggest MIF as a critical effector of
      organ injury in SLE.

PMID- 17015760
TI  - Amelioration of mercury-induced autoimmunity by 4-1BB.
AB  - In certain strains of mice, subtoxic doses of HgCl2 (mercuric chloride; mercury)
      induce a complex autoimmune condition characterized by the production of
      antinucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1/IgE
      Abs, and deposition of renal immune complexes. 4-1BB is an important T cell
      costimulatory molecule that has been implicated in T cell proliferation and
      cytokine production, especially production of IFN-gamma. To elucidate T cell
      control mediated by the 4-1BB signaling pathway in this syndrome, we assessed the
      effect of administering agonistic anti-4-1BB mAb on mercury-induced autoimmunity.
      Groups of A.SW mice (H-2s) received mercury/control Ig or mercury/anti-4-1BB or
      PBS alone. Anti-4-1BB mAb treatment resulted in a dramatic reduction of mercury
      induced antinucleolar Ab titers, serum IgG1/IgE induction, and renal Ig
      deposition. These effects may be related to the present finding that anti-4-1BB
      mAb decreases B cell numbers and function. The anti-4-1BB mAb-treated mercury
      group also showed a marked reduction in Th2-type cytokines but an increase in Th1
      type cytokines and chemokines. Increased IFN-gamma production due to anti-4-1BB
      mAb treatment appears to be responsible for the observed B cell defects because
      neutralization of IFN-gamma in vivo substantially restored B cell numbers and
      partly restored IgG1/IgE. Collectively, our results indicate that 4-1BB mAb can
      down-regulate mercury-induced autoimmunity by affecting B cell function in an IFN
      gamma-dependent manner and thus, preventing the development of autoantibody
      production and tissue Ig deposition.

PMID- 17015761
TI  - Reduced frequency, diversity, and function of human T cell leukemia virus type 1
      specific CD8+ T cell in adult T cell leukemia patients.
AB  - Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be
      immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in
      vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to
      be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers
      (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific
      CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of
      HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector
      molecules (IFN-gamma, perforin, and granzyme B). Overall frequency of subjects
      possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53
      vs 90%; p = 0.001), whereas the difference in Env-specific CD8+ T cells was not
      statistically significant. AC possessed Tax11-19/HLA-A*0201-specific tetramer+
      cells by 90% and Tax301-309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC
      recognized more than one epitope. In contrast, ATL recognized only Tax11-19 with
      HLA-A*0201 and Tax301-309 with HLA-A*2402 at frequencies of 30 and 55%. There
      were also significant differences in percentage of cells binding Tax11-19/HLA
      A*0201 and Tax301-309/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax
      CD8+ T cells in AC and ATL produced IFN-gamma in response to Tax. In contrast,
      perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was
      significant lower than that of AC. Frequency of Tax-specific CD8+ T cells in AC
      was related to proviral load in HLA-A*0201. These results suggest that decreased
      frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be
      one of the risks of ATL development.

PMID- 17015762
TI  - Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects
      rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and
      Bax translocation.
AB  - Rheumatoid arthritis (RA) synoviocytes are resistant to apoptosis and exhibit a
      transformed phenotype, which might be caused by chronic exposure to genotoxic
      stimuli including reactive oxygen species and growth factors. In this study, we
      investigated the role of vascular endothelial growth factor165 (VEGF165), a
      potent angiogenic factor, and its receptor in the apoptosis of synoviocytes. We
      demonstrated here that neuropilin-1, rather than fms-like tyrosine kinase-1 and
      kinase insert domain-containing receptor, is the major VEGF165 receptor in the
      fibroblast-like synoviocytes. Neuropilin-1 was highly expressed in the lining
      layer, infiltrating leukocytes, and endothelial cells of rheumatoid synovium. The
      production of VEGF165, a ligand for neuropilin, was significantly higher in the
      RA synoviocytes than in the osteoarthritis synoviocytes. The ligation of
      recombinant VEGF165 to its receptor prevented the apoptosis of synoviocytes
      induced by serum starvation or sodium nitroprusside (SNP). VEGF165 rapidly
      triggered phospho-Akt and phospho-ERK activity and then induced Bcl-2 expression
      in the rheumatoid synoviocytes. The Akt or ERK inhibitor cancelled the protective
      effect of VEGF165 on SNP-induced synoviocyte apoptosis. Moreover, VEGF165 blocks
      SNP-induced Bcl-2 down-regulation as well as SNP-induced Bax translocation from
      the cytosol to the mitochondria. The down-regulation of the neuropilin-1
      transcripts by short interfering RNA caused spontaneous synoviocyte apoptosis,
      which was associated with both the decrease in Bcl-2 expression and the increase
      in Bax translocation to mitochondria. Collectively, our data suggest that the
      interaction of VEGF165 with neuropilin-1 is crucial to the survival of rheumatoid
      synoviocytes and provide important implications for the abnormal growth of
      synoviocytes and therapeutic intervention in RA.

PMID- 17015763
TI  - Innate immune responses to human malaria: heterogeneous cytokine responses to
      blood-stage Plasmodium falciparum correlate with parasitological and clinical
      outcomes.
AB  - Taking advantage of a sporozoite challenge model established to evaluate the
      efficacy of new malaria vaccine candidates, we have explored the kinetics of
      systemic cytokine responses during the prepatent period of Plasmodium falciparum
      infection in 18 unvaccinated, previously malaria-naive subjects, using a highly
      sensitive, bead-based multiplex assay, and relate these data to peripheral
      parasite densities as measured by quantitative real-time PCR. These data are
      complemented with the analysis of cytokine production measured in vitro from
      whole blood or PBMC, stimulated with P. falciparum-infected RBC. We found
      considerable qualitative and quantitative interindividual variability in the
      innate responses, with subjects falling into three groups according to the
      strength of their inflammatory response. One group secreted moderate levels of
      IFN-gamma and IL-10, but no detectable IL-12p70. A second group produced
      detectable levels of circulating IL-12p70 and developed very high levels of IFN
      gamma and IL-10. The third group failed to up-regulate any significant
      proinflammatory responses, but showed the highest levels of TGF-beta.
      Proinflammatory responses were associated with more rapid control of parasite
      growth but only at the cost of developing clinical symptoms, suggesting that the
      initial innate response may have far-reaching consequences on disease outcome.
      Furthermore, the in vitro observations on cytokine kinetics presented here,
      suggest that intact schizont-stage infected RBC can trigger innate responses
      before rupture of the infected RBC.

PMID- 17015765
TI  - Autonomic cardiovascular responses to heme oxygenase inhibition in conscious
      rats.
AB  - Carbon monoxide (CO) is produced in the course of heme degradation from
      biliverdin by heme oxygenase (HO) in various tissues, including the central
      nervous system. Recent studies suggest the inhibition of HO activity increases
      arterial pressure mediated by the autonomic nervous system. The present study was
      designed to investigate the autonomic regulation of cardiovascular responses to
      inhibition of endogenous CO production by the HO inhibitor Zinc deuteroporphyrin
      2, 4-bis glycol (ZnDPBG) by using direct sympathetic nerve recordings in
      conscious, chronically instrumented rats. ZnDPBG induced increases in mean
      arterial pressure (MAP) (P<0.05) and renal sympathetic nerve activity (RSNA)
      (P<0.05) but no significant change in heart rate (P>0.05) in intact rats. In
      atropine-treated rats, ZnDPBG also induced increases in MAP (P<0.05) and RSNA
      (P<0.05) but no change in heart rate (P>0.05). In sinoaortic denervated rats,
      ZnDPBG induced increases in MAP (P<0.05), heart rate (P<0.05), and RSNA (P<0.05).
      ZnDPBG shifted the baroreflex curve for RSNA upward and to the right, which was
      characterized by increases in the maximum and minimum response and midpoint
      pressure without altering the maximum gain. These results indicate that
      inhibition of HO activity within the central nervous system causes
      sympathoexcitation, resulting in an increase in arterial pressure. We conclude
      that the CO/HO system plays an important role in cardiovascular regulation by
      modulating sympathetic tone.

PMID- 17015767
TI  - Beta-2 adrenergic receptor diplotype defines a subset of salt-sensitive
      hypertension.
AB  - Two genetic variants of the beta-2 adrenergic receptor, 46G>A and 79C>G, affect
      agonist-mediated receptor downregulation and vascular reactivity. We determined
      whether these variants were associated with hypertension, per se, blood pressure
      response to dietary sodium, 2 forms of salt-sensitive hypertension (low renin and
      nonmodulation), and the activity of the renin-angiotensin-aldosterone system.
      Included are 280 hypertensive and 65 normotensive white subjects who had the 2
      beta-2 adrenergic receptor genotypes available. Of all subjects, 171 hypertensive
      and 48 normotensive subjects had complete data for intermediate phenotyping and
      blood pressure evaluation on high- and low-sodium balance. The beta-2 adrenergic
      receptor variants were not associated with hypertension per se. However, among
      hypertensive subjects, the change (from low to high sodium balance) in mean
      arterial pressure differed significantly by genotype and by diplotype. Compared
      with all of the other diplotypes combined, 46AA/79CC was associated with a
      greater change in blood pressure. Furthermore, this diplotype was associated with
      low-renin (LR) hypertension (identifying 32% of the LR hypertensives), higher
      plasma aldosterone, and lower plasma renin and serum potassium levels. In
      conclusion, the 46AA/79CC diplotype is associated with greater blood pressure
      response to dietary sodium and higher odds of LR hypertension. We propose that
      the mechanism for the observed association is inadequate suppression of
      aldosterone with salt intake, implicating the beta-2 adrenergic receptor in the
      regulation of aldosterone secretion. This hypothesis was confirmed in isolated
      glomerulosa cells, where beta-2 adrenergic receptor stimulation increased
      aldosterone secretion, whereas blockade reduced the stimulated aldosterone
      response. Importantly, this association could only be detected with an
      intermediate and not a distant phenotype.

PMID- 17015768
TI  - Implication of chromosome 18 in hypertension by sibling pair and association
      analyses: putative involvement of the RKHD2 gene.
AB  - This study aims to test the implication of regions on chromosomes 9, 17, and 18
      in essential hypertension (EH) by combining sibling-pair linkage analysis and
      case-control association studies. The selection of these chromosomal regions is
      based on previous evidence of their implication in EH or in related phenotypes by
      comparative genomics in several rat models and from genome-wide linkage studies
      in humans. For the affected sibling-pair linkage analysis, 27 microsatellite
      markers were genotyped in 56 pedigrees from Spain with hypertensive sibling
      pairs. Linkage analysis showed significant excess allele sharing at the D18S474
      marker on 18q21.1, as shown by maximum likelihood of allele sharing methods
      (logarithm of odds=3.24; P=0.00011) and nonparametric linkage calculations
      (nonparametric linkage=3.32; P=0.00044). On the contrary, no significant results
      with any of the markers analyzed on chromosomes 9 and 17 were obtained. We
      further focused on the Ring finger and KH domain containing 2 (RKHD2) gene
      located 6 Kb distal from D18S474 and performed a case-control association study
      based on linkage disequilibrium in 112 hypertensive patients and 156 control
      subjects. We selected 2 RKHD2-tagged single nucleotide polymorphisms, rs1941958
      and rs1893379, covering, in terms of linkage disequilibrium, the entire gene, and
      observed a significant overrepresentation of the rs1941958G-rs1893379T RKHD2
      haplotype in the group of hypertensive patients in comparison with controls
      (2P=0.0004; odds ratio: 2.32). We also detected epistatic effects between the 2
      RKHD2 single nucleotide polymorphisms (2P=0.002; odds ratio: 2.48). Our data
      confirm the implication of chromosome 18 in EH and support a contribution of
      RKHD2 to the genetic susceptibility of this complex phenotype.

PMID- 17015769
TI  - Predictors of the evolution of microalbuminuria.

PMID- 17015770
TI  - Role of extracellular superoxide dismutase in the mouse angiotensin slow pressor
      response.
AB  - Low rates of angiotensin II (Ang II) infusion raise blood pressure, renal
      vascular resistance (RVR), NADPH oxidase activity, and superoxide. We tested the
      hypothesis that these effects are ameliorated by extracellular superoxide
      dismutase (EC-SOD). EC-SOD knockout (-/-) and wild type (+/+) mice were equipped
      with blood pressure telemeters and infused subcutaneously with Ang II (400 ng/kg
      per minute) or vehicle for 2 weeks. During vehicle infusion, EC-SOD -/- mice had
      significantly (P<0.05) higher MAP (+/+: 107+/-3 mm Hg versus -/-: 114+/-2 mm Hg;
      n=11 to 14), RVR, lipid peroxidation, renal cortical p22(phox) expression, and
      NADPH oxidase activity. Ang II infusion in EC-SOD +/+ mice significantly (P<0.05)
      increased MAP, RVR, p22(phox), NADPH oxidase activity, and lipid peroxidation.
      Ang II reduced SOD activity in plasma, aorta, and kidney accompanied by reduced
      renal EC-SOD expression. During Ang II infusion, both groups had similar values
      for MAP (+/+ Ang II: 125+/-3 versus -/- Ang II: 124+/-3 mmHg; P value not
      significant), RVR, NADPH oxidase activity, and lipid peroxidation. SOD activity
      in the kidneys of Ang II-infused mice was paradoxically higher in EC-SOD -/- mice
      (+/+: 8.8+/-1.2 U/mg protein(-1) versus -/-: 13.7+/-1.6 U/mg protein(-1); P<0.05)
      accompanied by a significant upregulation of mRNA and protein for Cu/Zn-SOD. In
      conclusion, EC-SOD protects normal mice against oxidative stress by attenuating
      renal p22(phox) expression, NADPH oxidase activation, and the accompanying renal
      vasoconstriction and hypertension. However, during an Ang II slow pressor
      response, renal EC-SOD expression is reduced and, in its absence, renal Cu/Zn-SOD
      is upregulated and may prevent excessive Ang II-induced renal oxidative stress,
      renal vasoconstriction, and hypertension.

PMID- 17015771
TI  - Reduction of blood pressure levels study group.

PMID- 17015773
TI  - Novel mechanisms of sympathetic regulation in chronic heart failure.

PMID- 17015774
TI  - NO differentially regulates neurotransmission to premotor cardiac vagal neurons
      in the nucleus ambiguus.
AB  - NO is involved in the neural control of heart rate, and NO synthase expressing
      neurons and terminals have been localized in the nucleus ambiguus where
      parasympathetic cardiac vagal preganglionic neurons are located; however, little
      is known about the mechanisms by which NO alters the activity of premotor cardiac
      vagal neurons. This study examines whether the NO donor sodium nitroprusside
      ([SNP] 100 micromol/L) and precursor, l-arginine (10 mmol/L), modulate excitatory
      and inhibitory synaptic neurotransmission to cardiac vagal preganglionic neurons.
      Glutamatergic, GABAergic, and glycinergic activity to cardiac vagal neurons was
      examined using whole-cell patch-clamp recordings in an in vitro brain slice
      preparation in rats. Both SNP, as well as l-arginine, increased the frequency of
      GABAergic neurotransmission to cardiac vagal preganglionic neurons but decreased
      the amplitude of GABAergic inhibitory postsynaptic currents. In contrast, both l
      arginine and SNP inhibited the frequency of glutamatergic and glycinergic
      synaptic events in cardiac vagal preganglionic neurons. SNP and l-arginine also
      decreased glycinergic inhibitory postsynaptic current amplitude, and this
      response persisted in the presence of tetrodotoxin. Inclusion of the NO synthase
      inhibitor 7-nitroindazole (100 mumol/L) prevented the l-arginine-evoked
      responses. These results demonstrate that NO differentially regulates excitatory
      and inhibitory neurotransmission, facilitating GABAergic and diminishing
      glutamatergic and glycinergic neurotransmission to cardiac vagal neurons.

PMID- 17015775
TI  - Salt reduction for preventing hypertension and cardiovascular disease: a
      population approach should include children.

PMID- 17015776
TI  - Role of endothelin receptors for renal protection and survival in hypertension:
      waiting for clinical trials.

PMID- 17015777
TI  - Late-onset endothelin-A receptor blockade reduces podocyte injury in homozygous
      Ren-2 rats despite severe hypertension.
AB  - We have recently found in male homozygous hypertensive Ren-2 transgenic rats
      (TGRs) fed a high-salt diet that early onset selective endothelin (ET) A (ET(A))
      or nonselective ET(A)/ET B (ET(B)) receptor blockade improved survival rate and
      reduced proteinuria, glomerulosclerosis, and cardiac hypertrophy, whereas
      selective ET(A) receptor blockade also significantly attenuated the rise in blood
      pressure. Because antihypertensive therapy in general is known to be more
      efficient when started at early age, our study was performed to determine whether
      onset of ET receptor blockade at a later age in animals with established
      hypertension will have similar protective effects as does early-onset therapy.
      Male homozygous TGRs and age-matched normotensive Hannover Sprague-Dawley rats
      were fed a high-salt diet between days 51 and 90 of age. TGRs received vehicle
      (untreated), the selective ET(A) receptor blocker atrasentan (ABT-627), or the
      nonselective ET(A)/ET(B) receptor blocker bosentan. Survival rates in untreated
      and bosentan-treated TGRs were 50% and 64%, respectively, whereas with
      atrasentan, survival rate of TGR was 96%, thus, similar to 93% in Hannover
      Sprague-Dawley rats. From day 60 on, systolic blood pressure in atrasentan
      treated TGRs was transiently lower (P<0.05) than in untreated or bosentan-treated
      TGRs. Glomerular podocyte injury was substantially reduced with atrasentan
      treatment independent of severe hypertension and strongly correlated with
      survival (P<0.001). Our data indicate that in homozygous TGR ET receptors play an
      important role also in established hypertension. Selective ET(A) receptor
      blockade not only reduces podocyte injury and end-organ damage but also improves
      growth and survival independently of hypertension.

PMID- 17015778
TI  - Genetic determinants of systolic and pulse pressure in an intercross between
      normotensive inbred rats.
AB  - By continuous monitoring of abdominal aortic blood pressure via telemetry in
      conscious rats, we have observed that systolic, diastolic, and pulse pressures of
      male Brown-Norway rats were all significantly lower than that of male Wistar
      Kyoto rats, despite the fact that all of the values in both strains were within
      normotensive ranges. Further analyses performed in 166 animals from the progeny
      of an F2 intercross between Brown-Norway and Wistar-Kyoto rats revealed that,
      despite a high correlation between systolic blood pressure and diastolic blood
      pressure, there was no correlation between pulse pressure and diastolic blood
      pressure, and the value of the correlation between systolic blood pressure and
      pulse pressure was lower than that of systolic blood pressure with diastolic
      blood pressure. Two major and highly significant (P<0.001) quantitative trait
      loci linked to pulse pressure were found on chromosome 4 (Pp1) and 16 (Pp2). Only
      suggestive quantitative trait loci were found for systolic blood pressure, but
      the strongest one (Sbp1) had the same peak and linkage probability profile as
      Pp1. Altogether, these data show that genetic determinants affecting pulse
      pressure in normotensive animals are either stronger or independent from the ones
      affecting systolic blood pressure and are of interest in light of evidence
      showing that pulse pressure is highly heritable in humans and that elevated pulse
      pressure is a predictor of cardiovascular risk.

PMID- 17015779
TI  - The adrenergic nervous system conversing with the adrenal cortex: new
      implications for salt-sensitive hypertension.

PMID- 17015780
TI  - Role of angiotensin type 2 receptors in vasodilation of resistance and
      capacitance vessels.

PMID- 17015781
TI  - Dissecting the causes of oxidative stress in an in vivo model of hypertension.

PMID- 17015782
TI  - Caveolin-dependent angiotensin II type 1 receptor signaling in vascular smooth
      muscle.

PMID- 17015783
TI  - Vascular gap junctions in hypertension.

PMID- 17015784
TI  - Stop Hypertension with the Acupuncture Research Program (SHARP): results of a
      randomized, controlled clinical trial.
AB  - Case studies and small trials suggest that acupuncture may effectively treat
      hypertension, but no large randomized trials have been reported. The Stop
      Hypertension with the Acupuncture Research Program pilot trial enrolled 192
      participants with untreated blood pressure (BP) in the range of 140/90 to 179/109
      mm Hg. The design of the trial combined rigorous methodology and adherence to
      principles of traditional Chinese medicine. Participants were weaned off
      antihypertensives before enrollment and were then randomly assigned to 3
      treatments: individualized traditional Chinese acupuncture, standardized
      acupuncture at preselected points, or invasive sham acupuncture. Participants
      received < or = 12 acupuncture treatments over 6 to 8 weeks. During the first 10
      weeks after random assignment, BP was monitored every 14 days, and
      antihypertensives were prescribed if BP exceeded 180/110 mm Hg. The mean BP
      decrease from baseline to 10 weeks, the primary end point, did not differ
      significantly between participants randomly assigned to active (individualized
      and standardized) versus sham acupuncture (systolic BP: -3.56 versus -3.84 mm Hg,
      respectively; 95% CI for the difference: -4.0 to 4.6 mm Hg; P=0.90; diastolic BP:
      -4.32 versus -2.81 mm Hg, 95% CI for the difference: -3.6 to 0.6 mm Hg; P=0.16).
      Categorizing participants by age, race, gender, baseline BP, history of
      antihypertensive use, obesity, or primary traditional Chinese medicine diagnosis
      did not reveal any subgroups for which the benefits of active acupuncture
      differed significantly from sham acupuncture. Active acupuncture provided no
      greater benefit than invasive sham acupuncture in reducing systolic or diastolic
      BP.

PMID- 17015785
TI  - Acupuncture for hypertension: can 2500 years come to an end?

PMID- 17015786
TI  - Percutaneous implantation of the CoreValve self-expanding valve prosthesis in
      high-risk patients with aortic valve disease: the Siegburg first-in-man study.
AB  - BACKGROUND: The morbidity and mortality of surgical aortic valve replacement are
      increased in elderly patients with multiple high-risk comorbid conditions.
      Therefore, a prospective, single-center, nonrandomized study was performed in
      high-risk patients with aortic valve disease to evaluate the feasibility and
      safety of percutaneous implantation of a novel self-expanding aortic valve
      bioprosthesis (CoreValve). METHODS AND RESULTS: Symptomatic high-risk patients
      with an aortic valve area <1 cm2 were considered for enrollment. CoreValve
      implantation was performed under general anesthesia with extracorporeal support
      using the retrograde approach. Clinical follow-up and transthoracic
      echocardiography were performed after the procedure and at days 15 and 30 after
      device implantation to evaluate short-term patient and device outcomes. A total
      of 25 patients with symptomatic aortic valve stenosis (mean gradient before
      implantation, 44.2+/-10.8 mm Hg) and multiple comorbidities (median logistic
      EuroScore, 11.0%) were enrolled. Device success and procedural success were
      achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device
      implantation resulted in a marked reduction in the aortic valve gradients (mean
      gradient after implantation, 12.4+/-3.0 mm Hg; P<0.0001). The mean aortic
      regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral
      events occurred in 8 patients (32%), including mortality in 5 patients (20%).
      Among 18 patients with device success surviving to discharge, no adverse events
      occurred within 30 days after leaving the hospital. CONCLUSIONS: Percutaneous
      implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk
      patients with aortic stenosis with or without aortic regurgitation is feasible
      and, when successful, results in marked hemodynamic and clinical improvement.

PMID- 17015787
TI  - Direct vascular effects of protease-activated receptor type 1 agonism in vivo in
      humans.
AB  - BACKGROUND: Protease-activated receptor type 1 (PAR-1) has been proposed as the
      principal thrombin receptor in humans, although its actions in vivo have not been
      defined. The aim of the present study was to determine the direct vascular
      actions of PAR-1 agonism in humans. METHODS AND RESULTS: Dorsal hand vein
      diameter was measured by the Aellig technique in 14 healthy volunteers during
      local intravenous SFLLRN (PAR-1 agonist; 0.05 to 15 nmol/min) and SLIGKV (PAR-2
      agonist; 1.6 to 160 nmol/min) infusions. The venous effects of SFLLRN were
      further assessed in the presence or absence of norepinephrine or the glycoprotein
      IIb/IIIa antagonist tirofiban. Forearm blood flow was measured by venous
      occlusion plethysmography in 16 volunteers during infusion of SFLLRN (1 to 50
      nmol/min), SLIGKV (160 to 800 nmol/min), and the endothelium-dependent
      vasodilator bradykinin (100 to 1000 pmol/min). Platelet-monocyte binding (a
      sensitive measure of platelet activation) and plasma tissue plasminogen activator
      (tPA), plasminogen-activator inhibitor 1, and von Willebrand factor
      concentrations were measured at intervals throughout the study. SFLLRN caused
      dose-dependent venoconstriction (P<0.001) that was unaffected by norepinephrine
      or tirofiban co-infusion. In forearm resistance vessels, SFLLRN increased forearm
      blood flow (P<0.001), tPA release (P<0.001), and platelet-monocyte binding
      (P<0.0001) without affecting plasma plasminogen-activator inhibitor 1 or von
      Willebrand factor concentrations. SLIGKV caused venous (P<0.001) and arterial
      (P<0.01) dilatation without tPA release. CONCLUSIONS: We have demonstrated that
      PAR-1 agonism causes platelet activation, venous constriction, arterial
      dilatation, and tPA release in vivo in humans. These unique and contrasting
      effects provide important insights into the physiological and pathophysiological
      role of thrombin in the human venous and arterial circulations.

PMID- 17015788
TI  - Cardiac troponin I but not cardiac troponin T induces severe autoimmune
      inflammation in the myocardium.
AB  - BACKGROUND: Cardiac troponins in blood are the most preferred markers of
      myocardial damage. The fact that they are normally not found in the circulation
      provides a high level of clinical sensitivity and specificity even when cardiac
      lesions are small. After myocardial injury, the troponins enter the circulation,
      where they can be used for diagnosis of acute coronary syndromes. Thus, the
      cardiac troponins are paramount for disease classification and risk
      stratification. However, little is known about the long-term effects of the
      released troponins on cardiac function. METHODS AND RESULTS: In this study we
      prepared recombinant murine cardiac troponin I (mc-TnI) and murine cardiac
      troponin T and used them to immunize mice. We report that A/J mice immunized with
      mc-TnI developed severe inflammation of the myocardium with increased expression
      of inflammatory chemokines RANTES (regulated on activation normal T cell
      expressed and secreted), monocyte chemoattractant protein-1, macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2, T-cell activation gene 3,
      and eotaxin and chemokine receptors CCR1, CCR2, and CCR5. The inflammation was
      followed by cardiomegaly, fibrosis, reduced fractional shortening, and 30%
      mortality over 270 days. In contrast, mice immunized with murine cardiac troponin
      T or with the control buffer showed little or no inflammation and no death.
      Furthermore, we demonstrate that mice preimmunized with mc-TnI before left
      anterior descending coronary artery ligation showed greater infarct size, more
      fibrosis, higher inflammation score, and reduced fractional shortening.
      CONCLUSIONS: Overall, our results show for the first time that provocation of an
      autoimmune response to mc-TnI induces severe inflammation in the myocardium
      followed by fibrosis and heart failure with increased mortality in mice.

PMID- 17015789
TI  - Midkine plays a protective role against cardiac ischemia/reperfusion injury
      through a reduction of apoptotic reaction.
AB  - BACKGROUND: Midkine (MK) is a heparin-binding growth factor involved in diverse
      biological phenomena, eg, neural survival, carcinogenesis, and tissue repair. MK
      could have a protective action against ischemia/reperfusion (I/R) injury in the
      heart, because MK was shown to have cytoprotective activity in cultured neurons
      and tumor cells. We investigated this hypothesis in mice with and without genetic
      MK deletion. METHODS AND RESULTS: Myocardial injury after I/R was produced by
      transient occlusion of coronary arteries. In wild-type (Mdk+/+) mice, MK
      expression was increased after I/R in the periinfarct area. Infarct size/area at
      risk 24 hours after I/R in MK-deficient (Mdk-/-) mice was larger than in Mdk+/+
      mice (55.4+/-9.1% versus 32.1+/-5.3%, P<0.05). Terminal dUTP nick end-labeling
      positive myocyte population in the periinfarct area in Mdk-/- mice was higher
      than in Mdk+/+ mice (6.8+/-0.9% versus 3.2+/-0.6%, P<0.05). Left ventricular
      fractional shortening 24 hours after I/R in Mdk-/- mice was significantly less
      than that in Mdk+/+ mice (34.3+/-4.4% versus 50.8+/-2.1%, P<0.05). Supplemental
      application of MK protein to left ventricle of Mdk-/- mice at the time of I/R
      resulted in reduction of the infarct size. Application of exogenous MK to
      cultured cardiomyocytes resulted in increased Bcl-2 expression and decreased
      apoptosis after hypoxia/reoxygenation. CONCLUSIONS: These results suggest that MK
      plays a protective role against I/R injury, most likely through a prevention of
      apoptotic reaction. MK is a potentially important new molecular target for
      treatment of ischemic heart disease.

PMID- 17015790
TI  - Implications of the failure to identify high-risk electrocardiogram findings for
      the quality of care of patients with acute myocardial infarction: results of the
      Emergency Department Quality in Myocardial Infarction (EDQMI) study.
AB  - BACKGROUND: The impact of misinterpretation of the ECG in patients with acute
      myocardial infarction (AMI) in the emergency department (ED) setting is not well
      known. Our goal was to assess the prevalence of the failure to identify high-risk
      ECG findings in ED patients with AMI and to determine whether this failure is
      associated with lower-quality care. METHODS AND RESULTS: In a retrospective
      cohort study of consecutive patients presenting to 5 EDs in California and
      Colorado from July 1, 2000, through June 30, 2002, with confirmed AMI (n=1684),
      we determined the frequency of the failure by the treating provider to identify
      significant ST-segment depressions, ST-segment elevations, or T-wave inversions
      on the presenting ECG. In multivariable models, we assessed the relationship
      between missed high-risk ECG findings and evidence-based therapy in the ED after
      adjustment for patient characteristics and site of care. High-risk ECG findings
      were not documented in 201 patients (12%). The failure to identify high-risk
      findings was independently associated with a higher odds of not receiving
      treatment among ideal candidates for aspirin (odds ratio [OR], 2.13; 95%
      confidence interval [CI], 1.51 to 2.94), beta-blockers (OR, 1.85; 95% CI, 1.14 to
      3.03), and reperfusion therapy (OR, 7.69; 95% CI, 3.57 to 16.67). Among patients
      with missed high-risk ECG findings, in-hospital mortality was 7.9% compared with
      4.9% among those without missed findings (P=0.1). CONCLUSIONS: The failure to
      identify high-risk ECG findings in patients with AMI results in lower-quality
      care in the ED. Systematic processes to improve ECG interpretation may have
      important implications for patient treatment and outcomes.

PMID- 17015791
TI  - High serum C-reactive protein level is not an independent predictor for stroke:
      the Rotterdam Study.
AB  - BACKGROUND: Current guidelines recommend the assessment of C-reactive protein
      (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction.
      Recent studies have put forward that although elevated CRP is a risk factor for
      cardiovascular disease, it is not helpful in the prediction of cardiovascular
      disease risk. We studied the importance of CRP as a risk factor and as a risk
      predictor of future stroke. METHODS AND RESULTS: The present study was based on
      6430 participants of the Rotterdam Study who at baseline (1990-1993) were > or =
      55 years of age, were stroke free, and had blood taken. Strokes were classified
      as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further
      subclassified. Whether stroke risk varied with baseline CRP serum levels was
      assessed with Cox proportional hazards models. Whether CRP was helpful in the
      prediction of individual stroke risk was assessed with receiver operating
      characteristic curves and by comparing the distribution of strokes between
      predicted risk strata. During an average of 8.2 years of follow-up, 498 first
      ever strokes occurred. High CRP levels were significantly associated with risk of
      any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence
      interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard
      ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels
      into account did not improve the individual stroke risk prediction, however,
      regardless of whether it was based on the Framingham stroke risk score or on age
      and sex only. CONCLUSIONS: Although CRP levels are associated with stroke risk,
      their use in the assessment of individual stroke risk seems limited.

PMID- 17015792
TI  - Assessment of coronary artery disease by cardiac computed tomography: a
      scientific statement from the American Heart Association Committee on
      Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and
      Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology.

PMID- 17015793
TI  - Drawbacks and prognostic value of formulas estimating renal function in patients
      with chronic heart failure and systolic dysfunction.
AB  - BACKGROUND: Renal function is an important risk marker for morbidity and
      mortality in chronic heart failure (CHF) and is often estimated with the use of
      creatinine-based formulas. However, these formulas have never been validated in a
      wide range of CHF patients. We validated 3 commonly used formulas estimating
      glomerular filtration rate (GFR) with true GFR in CHF patients. Furthermore, we
      compared the prognostic value of these formulas for cardiovascular outcome with
      that of true GFR during 12 months of follow-up. METHODS AND RESULTS: In 110 CHF
      patients (age, 57+/-11.7 years; left ventricular ejection fraction, 0.27+/-0.09;
      NYHA class, 2.5+/-0.9), we measured 125I-iothalamate clearance. Cockcroft-Gault
      (GFR(cg)), Modification of Diet in Renal Disease (MDRD), and simplified MDRD
      (sMDRD) equations were used as creatinine-based renal function estimations.
      Furthermore, 24-hour creatinine clearance (CrCl) was determined. CrCl and GFR(cg)
      were the most accurate. MDRD was most precise formula, although it was also
      highly biased. All formulas overestimated in the lower ranges and underestimated
      in the upper ranges of the GFR corrected for body surface area. The predictive
      performance of the formulas was best in severe CHF (NYHA classes III and IV). The
      prognostic value of CrCl and MDRD for cardiovascular outcome was comparable to
      that of GFR, the sMDRD was slightly less, and the GFR(cg) had a significantly
      worse prognostic value. CONCLUSIONS: In the more severe ranges of CHF, creatinine
      based formulas and CrCl corrected for body surface area appeared to be more
      precise and accurate in estimating true GFR corrected for body surface area. The
      MDRD formula is the most precise and has a good prognostic value, whereas the
      sMDRD is slightly less accurate but uses fewer parameters, which makes this
      formula a practical alternative in clinical practice.

PMID- 17015794
TI  - T-cell immunity to subclinical cytomegalovirus infection reduces cardiac
      allograft disease.
AB  - BACKGROUND: Asymptomatic cytomegalovirus (CMV) replication is frequent after
      cardiac transplantation in recipients with pretransplantation CMV infection. How
      subclinical viral replication influences cardiac allograft disease remains poorly
      understood, as does the importance of T-cell immunity in controlling such
      replication. METHODS AND RESULTS: Thirty-nine cardiac recipients who were
      pretransplantation CMV antibody positive were longitudinally studied for
      circulating CMV-specific CD4 and CD8 T-cell responses, CMV viral load in blood
      neutrophils, and allograft rejection during the first posttransplantation year.
      Nineteen of these recipients were also analyzed for changes of coronary artery
      intimal, lumen, and whole-vessel area. All recipients received early prophylactic
      therapy with ganciclovir. No recipients developed overt CMV disease. Those with
      detectable levels of CMV-specific CD4 T cells in the first month after
      transplantation were significantly protected from high mean and peak
      posttransplantation viral load (P<0.05), acute rejection (P<0.005), and loss of
      allograft coronary artery lumen (P<0.05) and of whole-vessel area (P<0.05)
      compared with those who lacked this immune response. The losses of lumen and
      vessel area were both significantly correlated with the time after
      transplantation at which a CD4 T-cell response was first detected (P<0.05) and
      with the cumulative graft rejection score (P<0.05). CONCLUSIONS: The early
      control of subclinical CMV replication after transplantation by T-cell immunity
      may limit cardiac allograft rejection and vascular disease. Interventions to
      increase T-cell immunity might be clinically useful in limiting these adverse
      viral effects.

PMID- 17015795
TI  - Presentation, patterns of myocardial damage, and clinical course of viral
      myocarditis.
AB  - BACKGROUND: Enteroviruses and adenoviruses have been considered the most common
      causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6
      (HHV6) are increasingly found in endomyocardial biopsy samples. METHODS AND
      RESULTS: Consequently, our aim was to evaluate the prevalence and clinical
      presentation of cardiac PVB19 and/or HHV6 infection in a cohort of myocarditis
      patients and to follow its clinical course. In addition, we sought to demonstrate
      patterns of myocardial damage and to determine predictors for chronic heart
      failure. Our study design consisted of a cardiovascular magnetic resonance
      protocol as well as endomyocardial biopsies in the myocardial region affected as
      indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients
      were enrolled by clinical criteria. In the group of myocarditis patients (n=87),
      PVB19 (n=49), HHV6 (n=16), and combined PVB19/HHV6 infections (n=15) were
      detected most frequently. The remaining patients were diagnosed with healing
      myocarditis (n=15) or did not have myocarditis (n=26). Patients with PVB19
      presented in a manner similar to that of myocardial infarction; most had typical
      subepicardial late gadolinium enhancement in the lateral wall and recovered
      within months. Conversely, patients with HHV6 and especially with HHV6/PVB19
      myocarditis presented with new onset of heart failure, had septal late gadolinium
      enhancement, and frequently progressed toward chronic heart failure. CONCLUSIONS:
      Our data indicate that PVB19 and HHV6 are the most important causes for viral
      myocarditis in Germany and that the clinical presentation is related to the type
      of virus. Furthermore, clinical presentation, type of virus, and pattern of
      myocardial damage are related to the clinical course.

PMID- 17015796
TI  - The chemokine and chemokine receptor profile of infiltrating cells in the wall of
      arteries with cardiac allograft vasculopathy is indicative of a memory T-helper 1
      response.
AB  - BACKGROUND: Despite improvement in short-term patient survival after heart
      transplantation (HTx), long-term survival rates have not improved much, mainly
      because of cardiac allograft vasculopathy (CAV). Cytokines and chemokines are
      considered to play an important role in CAV development. METHODS AND RESULTS: We
      focused on coronary arteries of HTx patients and made an inventory of the
      infiltrating cells and the expression of cytokines as well as chemokines and
      chemokine receptors (C+CR) in the different layers of the vessel wall with CAV.
      Tissue slides were stained for a variety of cell markers (CD3, CD4, CD8, CD20,
      CD68, CD79a), chemokines (monokine induced by interferon [MIG], interferon
      inducible protein 10 [IP-10], interferon-inducible T cell-alpha chemoattractant
      [ITAC], RANTES [regulated on activation normal T cell expressed and secreted],
      and fractalkine), and chemokine receptors (CXCR3, CCR5, and CX3CR1). In reference
      coronary arteries (not transplanted), almost no infiltrating cells were found,
      and in transplanted hearts with CAV (HTx+CAV), a large number of T cells were
      observed (CD4:CD8=2:1), mainly localized in the neointima and adventitia. Most of
      these T cells appeared to be activated (human leukocyte antigen DR positive).
      Coronary arteries from transplanted hearts without CAV (HTx-CAV), HTx+CAV, and
      references were also analyzed for cytokine and C+CR mRNA expression with the use
      of quantitative polymerase chain reaction. Interferon-gamma was highly expressed
      in HTx+CAV compared with HTx-CAV. Interleukin-4 and interleukin-10 were expressed
      at the same level in both HTx groups and references. In HTx+CAV, all C+CR, but
      especially the T-helper 1 (TH1) C+CR, were more abundant than in the HTx-CAV and
      references. However, TH2 CCR4 expression did not differ significantly between
      both HTx groups. CONCLUSIONS: In coronary arteries with CAV, most T cells are
      CD4+ and express human leukocyte antigen DR. These activated TH cells are mainly
      memory TH1 cells on the basis of their C+CR profile and cytokine expression.

PMID- 17015797
TI  - Images in cardiovascular medicine. Sixty-four-multislice computed tomography
      image of a ruptured coronary plaque.

PMID- 17015798
TI  - Images in cardiovascular medicine. Therapeutic hypothermia-related torsade de
      pointes.

PMID- 17015799
TI  - Images in cardiovascular medicine. Rapid resolution of massive lung abscesses
      complicating tricuspid-valve endocarditis.

PMID- 17015800
TI  - Letter by Schinkel et al regarding article, "Projected valve area at normal flow
      rate improves the assessment of stenosis severity in patients with low-flow, low
      gradient aortic stenosis: the multicenter TOPAS (Truly or Pseudo-Severe Aortic
      Stenosis) study".

PMID- 17015801
TI  - A view from the Czech Republic.

PMID- 17015802
TI  - Exercise training in pulmonary hypertension: implications for the evaluation of
      drug trials.

PMID- 17015803
TI  - Smoking bans prevent heart attacks.

PMID- 17015804
TI  - Exploring mitochondria in the intact ischemic heart: advancing technologies to
      image intracellular function.

PMID- 17015805
TI  - Nitroso-redox interactions in the cardiovascular system.

PMID- 17015806
TI  - Hypothesis testing: proportions.

PMID- 17015807
TI  - The Wurgengel.

PMID- 17015808
TI  - Comparative effectiveness of antipsychotic drugs. A commentary on: Cost Utility
      Of The Latest Antipsychotic Drugs In Schizophrenia Study (CUtLASS 1) and Clinical
      Antipsychotic Trials Of Intervention Effectiveness (CATIE).

PMID- 17015809
TI  - Outcomes, costs, and policy caution. A commentary on: the Cost Utility of the
      Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).

PMID- 17015810
TI  - Randomized controlled trial of the effect on Quality of Life of second- vs first
      generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest
      Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1).
AB  - CONTEXT: Second-generation (atypical) antipsychotics (SGAs) are more expensive
      than first-generation (typical) antipsychotics (FGAs) but are perceived to be
      more effective, with fewer adverse effects, and preferable to patients. Most
      evidence comes from short-term efficacy trials of symptoms. OBJECTIVE: To test
      the hypothesis that in people with schizophrenia requiring a change in treatment,
      SGAs other than clozapine are associated with improved quality of life across 1
      year compared with FGAs. DESIGN: A noncommercially funded, pragmatic, multisite,
      randomized controlled trial of antipsychotic drug classes, with blind assessments
      at 12, 26, and 56 weeks using intention-to-treat analysis. SETTING: Fourteen
      community psychiatric services in the English National Health Service.
      PARTICIPANTS: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV
      schizophrenia and related disorders assessed for medication review because of
      inadequate response or adverse effects. INTERVENTIONS: Randomized prescription of
      either FGAs or SGAs (other than clozapine), with the choice of individual drug
      made by the managing psychiatrist. MAIN OUTCOME MEASURES: Quality of Life Scale
      scores, symptoms, adverse effects, participant satisfaction, and costs of care.
      RESULTS: The primary hypothesis of significant improvement in Quality of Life
      Scale scores during the year after commencement of SGAs vs FGAs was excluded.
      Participants in the FGA arm showed a trend toward greater improvements in Quality
      of Life Scale and symptom scores. Participants reported no clear preference for
      either drug group; costs were similar. CONCLUSIONS: In people with schizophrenia
      whose medication is changed for clinical reasons, there is no disadvantage across
      1 year in terms of quality of life, symptoms, or associated costs of care in
      using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns
      of drug discontinuation accounted for the result.

PMID- 17015811
TI  - Smaller neocortical gray matter and larger sulcal cerebrospinal fluid volumes in
      neuroleptic-naive women with schizotypal personality disorder.
AB  - CONTEXT: Structural brain abnormalities, including larger cerebrospinal fluid
      (CSF) volumes, have been observed in men diagnosed as having schizotypal
      personality disorder (SPD). OBJECTIVES: To determine whether women with SPD have
      abnormalities similar to those of men with SPD and to elucidate specific SPD
      regional volume deficits and symptom correlations. DESIGN: Naturalistic study.
      SETTING AND PARTICIPANTS: Thirty neuroleptic-naive women with SPD and 29 female
      control subjects, both recruited from the community. Participants were group
      matched for age, parental socioeconomic status, handedness, and IQ.
      INTERVENTIONS: A new segmentation method was applied to magnetic resonance images
      to automatically parcel the images into CSF, gray matter, and white matter. The
      neocortex was manually separated from subcortical and other nonneocortical
      structures. Voxel-based morphometry was applied to determine global and regional
      volume deficits. MAIN OUTCOME MEASURES: Left and right neocortical gray matter,
      white matter, and CSF relative volumes as well as clinical symptoms from the
      Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire
      Brief Version. RESULTS: Smaller left (3.84%) and right (3.83%) neocortical gray
      matter relative volumes associated with larger left (9.66%) and right (9.61%)
      sulcal CSF relative volumes were found in women with SPD compared with controls.
      Voxel-based morphometry showed that the neocortical deficits in SPD were
      especially prominent in the left superior and middle temporal gyri, left inferior
      parietal region with postcentral gyrus, and right superior frontal and inferior
      parietal gyri. In the SPD group, larger lateral ventricle volumes correlated with
      more severe symptoms on the Structured Interview for Schizotypy and the
      Schizotypal Personality Questionnaire-Brief Version. CONCLUSIONS: The smaller
      neocortical gray matter volume and larger sulcal CSF volume provide evidence of
      the brain basis of this personality disorder and emphasize the communality of
      brain abnormalities in the schizophrenia spectrum.

PMID- 17015812
TI  - Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and
      bipolar disorder in a Northern Swedish, isolated population.
AB  - CONTEXT: Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin (5
      HT) biosynthetic pathway responsible for the regulation of serotonin levels.
      Tryptophan hydroxylase 2 (TPH2) was found to be solely expressed in the brain and
      therefore considered an important susceptibility gene in psychiatric disorders.
      OBJECTIVE: To determine the role of the brain-specific TPH2 gene in unipolar (UP)
      disorder and bipolar (BP) disorder in a northern Swedish, isolated population.
      DESIGN: HapMap-based haplotype-tagging single nucleotide polymorphism (htSNP)
      patient-control association study. SETTING: A northern Swedish, isolated
      population. PARTICIPANTS: One hundred thirty-five unrelated patients with UP
      disorder, 182 unrelated patients with BP disorder, and 364 unrelated control
      individuals. RESULTS: Significant allelic association was identified in our UP
      disorder association sample for an htSNP located in the 5' promoter region
      (rs11178997; P = .001). Haplotype analysis supported this significant result by
      the presence of a protective factor on hapblock 2 (P(specific) = .002). In the BP
      disorder association sample, single-marker association identified a significant
      htSNP in the upstream regulatory region (rs4131348; P = .004). Moreover,
      haplotype analysis in the BP disorder sample showed that the same htSNPs from
      hapblock 2 associated with UP disorder were also significantly associated with BP
      disorder (P(specific) = .002). CONCLUSIONS: Haplotype-based analysis of TPH2 in
      patients with UP and BP disorder and controls from northern Swedish descent
      provides preliminary evidence for protective association in both disorders and
      thus supports a central role for TPH2 in the pathogenesis of affective disorders.

PMID- 17015813
TI  - Personality and major depression: a Swedish longitudinal, population-based twin
      study.
AB  - CONTEXT: Prior studies suggest that the personality traits of neuroticism and
      extroversion may be related to the liability to major depression (MD). OBJECTIVE:
      To clarify the magnitude and nature of the association between neuroticism and
      extroversion and the risk for MD. DESIGN: Longitudinal population-based twin
      cohort. SETTING: General community. PARTICIPANTS: A total of 20 692 members of
      same-sex twin pairs from the population-based Swedish Twin Registry who completed
      a self-report questionnaire assessing neuroticism and extroversion in 1972 and
      1973 and were personally interviewed for lifetime history of MD more than 25
      years later.Main Outcome Measure Lifetime history of modified DSM-IV MD. RESULTS:
      Levels of neuroticism strongly predicted the risks for both lifetime and new
      onset MD. Twin modeling indicated that the association between neuroticism and MD
      resulted largely from shared genetic risk factors, with a genetic correlation of
      +0.46 to +0.47. Levels of extroversion were weakly and inversely related to the
      risks for lifetime and new-onset MD. This effect disappeared when we controlled
      for the level of neuroticism. Twin modeling produced similar results.
      CONCLUSIONS: Results from both longitudinal and genetic analyses support the
      hypothesis that neuroticism strongly reflects the liability to MD. This
      association arises largely because neuroticism indexes the genetic risk for
      depressive illness. However, substantial proportions of the genetic vulnerability
      to MD are not reflected in neuroticism. By contrast, extroversion is only weakly
      related to risk for MD.

PMID- 17015814
TI  - Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized,
      placebo-controlled clinical trial.
AB  - CONTEXT: The need for improved therapeutic agents that more quickly and
      effectively treat depression is critical. In a pilot study we evaluated the role
      of the cholinergic system in cognitive symptoms of depression and unexpectedly
      observed rapid reductions in depression severity following the administration of
      the antimuscarinic drug scopolamine hydrobromide (4 microg/kg intravenously)
      compared with placebo (P = .002). Subsequently a clinical trial was designed to
      assess more specifically the antidepressant efficacy of scopolamine. OBJECTIVE:
      To evaluate scopolamine as a potential antidepressant agent. DESIGN: Two studies
      were conducted: a double-blind, placebo-controlled, dose-finding study followed
      by a double-blind, placebo-controlled, crossover clinical trial. SETTING: The
      National Institute of Mental Health. Patients Currently depressed outpatients
      aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive
      disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18
      completed the trial. INTERVENTIONS: Multiple sessions including intravenous
      infusions of placebo or scopolamine hydrobromide (4 microg/kg). Individuals were
      randomized to a placebo/scopolamine or scopolamine/placebo sequence (series of 3
      placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5
      days apart. MAIN OUTCOME MEASURES: Psychiatric evaluations using the Montgomery
      Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were
      performed to assess antidepressant and antianxiety responses to scopolamine.
      RESULTS: The placebo/scopolamine group showed no significant change during
      placebo infusion vs baseline; reductions in depression and anxiety rating scale
      scores (P<.001 for both) were observed after the administration of scopolamine
      compared with placebo. The scopolamine/placebo group also showed reductions in
      depression and anxiety rating scale scores (P<.001 for both) after the
      administration of scopolamine, relative to baseline, and these effects persisted
      as they received placebo. In both groups, improvement was significant at the
      first evaluation after scopolamine administration (P< or =.002). CONCLUSION:
      Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred
      in currently depressed patients who predominantly had poor prognoses.

PMID- 17015815
TI  - Controlled, blindly rated, direct-interview family study of a prepubertal and
      early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and
      comorbidity.
AB  - CONTEXT: A key question is whether a prepubertal and early-adolescent bipolar I
      disorder phenotype (PEA-BP-I) is the same illness as adult BP-I. This question
      arises because of the greater severity, longer current episode duration,
      preponderance of mania, and high rates of ultradian rapid cycling and comorbid
      attention-deficit/hyperactivity disorder (ADHD) in PEA-BP-I. OBJECTIVES: To
      examine morbid risk (MR) of BP-I in first-degree relatives of PEA-BP-I, ADHD, and
      healthy control probands, as well as imprinting, sibling recurrence risk, and
      anticipation. DESIGN: Controlled, blind direct interview. There were no family
      psychopathology exclusions for any proband group. SETTING: University medical
      school research unit. PARTICIPANTS: First-degree relatives 6 years and older (n =
      690) of 219 probands (95 with PEA-BP-I, 47 with ADHD, and 77 healthy controls).
      The PEA-BP-I and ADHD probands were obtained by consecutive new case
      ascertainment, and healthy controls were from a random survey; proband diagnoses
      were validated via 4-year prospective follow-up. The PEA-BP-I probands had a mean
      +/- SD age of 10.8 +/- 2.6 years. Main Outcome Measure Morbid risk. RESULTS: The
      MR of BP-I was higher in relatives of PEA-BP-I probands compared with ADHD or
      healthy controls (P<.001 for both); the MR in relatives of ADHD and healthy
      controls was similar. The MR of BP-I in relatives with ADHD was higher (P<.001)
      and age at onset of BP-I was younger in parents with ADHD than in those without
      (P<.001). The MR of BP-I in relatives with oppositional, conduct, or antisocial
      disorders was higher than in those without (P<.001). Anticipation was evidenced
      by a younger age at onset of BP-I in probands than in their parents (P<.001). No
      imprinting was found. CONCLUSIONS: Findings support that PEA-BP-I and adult BP-I
      are the same diathesis, 7 to 8x greater familiality in child vs adult BP-I, and
      family study validation of PEA-BP-I, including its differentiation from ADHD.

PMID- 17015816
TI  - Phenomenology of children and adolescents with bipolar spectrum disorders.
AB  - CONTEXT: Children and adolescents who present with manic symptoms frequently do
      not meet the full DSM-IV criteria for bipolar I disorder (BP-I). OBJECTIVE: To
      assess the clinical presentation and family history of children and adolescents
      with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise
      specified (BP-NOS). DESIGN: Subjects and their primary caretaker were assessed by
      semistructured interview, and family psychiatric history was obtained from
      interview of the primary caretaker. SETTING: Outpatient and inpatient units at 3
      university centers. PARTICIPANTS: A total of 438 children and adolescents (mean
      +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n
      = 153). MAIN OUTCOME MEASURES: Lifetime psychiatric history and family history of
      psychiatric disorders. RESULTS: Youth with BP-NOS were not diagnosed as having BP
      I primarily because they did not meet the DSM-IV duration criteria for a manic or
      mixed episode. There were no significant differences among the BP-I and BP-NOS
      groups in age of onset, duration of illness, lifetime rates of comorbid
      diagnoses, suicidal ideation and major depression, family history, and the types
      of manic symptoms that were present during the most serious lifetime episode.
      Compared with youth with BP-NOS, subjects with BP-I had more severe manic
      symptoms, greater overall functional impairment, and higher rates of
      hospitalization, psychosis, and suicide attempts. Elevated mood was present in
      81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP
      II had higher rates of comorbid anxiety disorders compared with the other 2
      groups and had less functional impairment and lower rates of psychiatric
      hospitalization than the subjects with BP-I. CONCLUSIONS: Children and
      adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with
      that of youth with BP-I. Elevated mood is a common feature of youth with BP
      spectrum illness.

PMID- 17015817
TI  - Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.
AB  - CONTEXT: Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist
      recently approved for insomnia treatment. Most approved insomnia medications have
      potential for abuse and cause motor and cognitive impairment. OBJECTIVE: To
      evaluate the potential for abuse, subjective effects, and motor and cognitive
      impairing effects of ramelteon compared with triazolam, a classic benzodiazepine
      sedative-hypnotic drug. DESIGN: In this double-blind crossover study, each
      participant received oral doses of ramelteon (16, 80, or 160 mg), triazolam
      (0.25, 0.5, or 0.75 mg), and placebo during approximately 18 days. All
      participants received each treatment on different days. Most outcome measures
      were assessed at 0.5 hours before drug administration and repeatedly up to 24
      hours after drug administration. SETTING: Residential research facility.
      PARTICIPANTS: Fourteen adults with histories of sedative abuse. MAIN OUTCOME
      MEASURES: Subject-rated measures included items relevant to potential for abuse
      (eg, drug liking, street value, and pharmacological classification), as well as
      assessments of a broad range of stimulant and sedative subjective effects.
      Observer-rated measures included assessments of sedation and impairment. Motor
      and cognitive performance measures included psychomotor and memory tasks and a
      standing balance task. RESULTS: Compared with placebo, ramelteon (16, 80, and 160
      mg) showed no significant effect on any of the subjective effect measures,
      including those related to potential for abuse. In the pharmacological
      classification, 79% (11/14) of subjects identified the highest dose of ramelteon
      as placebo. Similarly, compared with placebo, ramelteon had no effect at any dose
      on any observer-rated or motor and cognitive performance measure. In contrast,
      triazolam showed dose-related effects on a wide range of subject-rated, observer
      rated, and motor and cognitive performance measures, consistent with its profile
      as a sedative drug with abuse liability. CONCLUSION: Ramelteon demonstrated no
      significant effects indicative of potential for abuse or motor and cognitive
      impairment at up to 20 times the recommended therapeutic dose and may represent a
      useful alternative to existing insomnia medications.

PMID- 17015818
TI  - Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6
      month randomized controlled trial.
AB  - CONTEXT: No large-scale posttraumatic stress disorder drug trials have been
      conducted to evaluate treatment effects beyond 12 weeks outside of those with
      selective serotonin reuptake inhibitors. OBJECTIVE: To evaluate the efficacy of
      venlafaxine extended release (ER), a serotonin norepinephrine reuptake inhibitor,
      in posttraumatic stress disorder. DESIGN: 6-month, double-blind, placebo
      controlled trial. SETTING: International study at 56 sites. Patients Adult
      outpatients (N = 329) with a primary diagnosis of posttraumatic stress disorder
      as defined in the DSM-IV, symptoms for 6 months or longer, and a 17-item
      Clinician-Administered Posttraumatic Stress Disorder Scale score of 60 or higher.
      Intervention Patients randomly assigned to receive flexible doses of venlafaxine
      ER (37.5-300 mg/d) or placebo for 24 weeks. MAIN OUTCOME MEASURES: Primary
      measure was the change from baseline in the Clinician-Administered Posttraumatic
      Stress Disorder Scale score. Secondary measures included remission, defined as a
      Clinician-Administered Posttraumatic Stress Disorder Scale score of 20 or lower,
      and changes in symptom cluster scores, frequency of remission, and time to
      remission. Measures of stress vulnerability, resilience, depression, quality of
      life, functioning, and global illness severity were also taken. RESULTS: Mean
      changes from baseline in Clinician-Administered Posttraumatic Stress Disorder
      Scale total scores at end point were -51.7 for venlafaxine ER and -43.9 for
      placebo (P = .006). Improvement was significantly greater for the venlafaxine ER
      group than for the placebo group in cluster scores for reexperiencing (P = .008)
      and avoidance/numbing (P = .006), but not for hyperarousal. Remission rates were
      50.9% for venlafaxine ER and 37.5% for placebo (P = .01). The venlafaxine ER
      group also showed significantly greater improvement at end point than the placebo
      group (P<.05) on all other reported outcome measures. The mean maximum daily dose
      of venlafaxine ER was 221.5 mg/d. Withdrawal rates were similar between groups
      with no significant difference in dropouts attributable to adverse events.
      CONCLUSION: In this study, venlafaxine ER was effective and well tolerated in
      short-term and continuation treatment of patients with posttraumatic stress
      disorder.

PMID- 17015819
TI  - Functional units in the olfactory system.

PMID- 17015820
TI  - The piggyBac transposon holds promise for human gene therapy.

PMID- 17015821
TI  - Of mice and sperm.

PMID- 17015822
TI  - Enzyme therapy in mannose receptor-null mucopolysaccharidosis VII mice defines
      roles for the mannose 6-phosphate and mannose receptors.
AB  - Enzyme replacement therapy (ERT) is available for several lysosomal storage
      diseases. Except for Gaucher disease, for which an enzyme with exposed mannosyl
      residues targets mannose receptors (MR) on macrophages, ERT targets primarily the
      mannose 6-phosphate receptor (MPR). Most recombinant lysosomal enzymes contain
      oligosaccharides with both terminal mannosyl and mannose 6-phosphate residues.
      Effective MPR-mediated delivery may be compromised by rapid clearance of infused
      enzyme by the MR on fixed tissue macrophages, especially Kupffer cells. To
      evaluate the impact of this obstacle to ERT, we introduced the MR-null mutation
      onto the mucopolysaccharidosis type VII (MPS VII) background and produced doubly
      deficient MR-/- MPS VII mice. The availability of both MR+/+ and MR-/- mice
      allowed us to study the effects of eliminating the MR on MR- and MPR-mediated
      plasma clearance and tissue distribution of infused phosphorylated (P) and
      nonphosphorylated (NP) forms of human beta-glucuronidase (GUS). In MR+/+ MPS VII
      mice, the MR clearance system predominated at doses up to 6.4 mg/kg P-GUS.
      Genetically eliminating the MR slowed plasma clearance of both P- and NP-GUS and
      enhanced the effectiveness of P-GUS in clearing storage in kidney, bone, and
      retina. Saturating the MR clearance system by high doses of enzyme also improved
      targeting to MPR-containing tissues such as muscle, kidney, heart, and
      hepatocytes. Although ablating the MR clearance system genetically is not
      practical clinically, blocking the MR-mediated clearance system with high doses
      of enzyme is feasible. This approach delivers a larger fraction of enzyme to MPR
      expressing tissues, thus enhancing the effectiveness of MPR-targeted ERT.

PMID- 17015823
TI  - The structure of human ADP-ribosylhydrolase 3 (ARH3) provides insights into the
      reversibility of protein ADP-ribosylation.
AB  - Posttranslational modifications are used by cells from all kingdoms of life to
      control enzymatic activity and to regulate protein function. For many cellular
      processes, including DNA repair, spindle function, and apoptosis, reversible mono
      and polyADP-ribosylation constitutes a very important regulatory mechanism.
      Moreover, many pathogenic bacteria secrete toxins which ADP-ribosylate human
      proteins, causing diseases such as whooping cough, cholera, and diphtheria.
      Whereas the 3D structures of numerous ADP-ribosylating toxins and related
      mammalian enzymes have been elucidated, virtually nothing is known about the
      structure of protein de-ADP-ribosylating enzymes. Here, we report the 3Dstructure
      of human ADP-ribosylhydrolase 3 (hARH3). The molecular architecture of hARH3
      constitutes the archetype of an all-alpha-helical protein fold and provides
      insights into the reversibility of protein ADP-ribosylation. Two magnesium ions
      flanked by highly conserved amino acids pinpoint the active-site crevice.
      Recombinant hARH3 binds free ADP-ribose with micromolar affinity and efficiently
      de-ADP-ribosylates poly- but not monoADP-ribosylated proteins. Docking
      experiments indicate a possible binding mode for ADP-ribose polymers and suggest
      a reaction mechanism. Our results underscore the importance of endogenous ADP
      ribosylation cycles and provide a basis for structure-based design of ADP
      ribosylhydrolase inhibitors.

PMID- 17015824
TI  - The HIV Env variant N283 enhances macrophage tropism and is associated with brain
      infection and dementia.
AB  - HIV infects tissue macrophages and brain microglia, which express lower levels of
      CD4 and CCR5 than CD4+ T cells in peripheral blood. Mechanisms that enhance HIV
      tropism for macrophages in the CNS and other tissues are not well understood.
      Here, we identify an HIV envelope glycoprotein (Env) variant in the CD4-binding
      site of gp120, Asn 283 (N283), that is present at a high frequency in brain
      tissues from AIDS patients with HIV-associated dementia (HAD). N283 increases
      gp120 affinity for CD4 by decreasing the gp120-CD4 dissociation rate, enhancing
      the capacity of HIV Envs to use low levels of CD4 for virus entry and increasing
      viral replication in macrophages and microglia. Structural modeling suggests that
      the enhanced ability of Envs with N283 to use low levels of CD4 is due to a
      hydrogen bond formed with Gln 40 of CD4. N283 is significantly more frequent in
      brain-derived Envs from HAD patients (41%; n=330) compared with non-HAD patients
      (8%; n=151; P<0.001). These findings suggest that the macrophage-tropic HIV Env
      variant N283 is associated with brain infection and dementia in vivo,
      representing an example of a HIV variant associated with a specific AIDS-related
      complication.

PMID- 17015825
TI  - Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking
      induced by environmental stress.
AB  - Alcoholism is a chronic relapsing disorder with substantial heritability.
      Uncovering gene-environment interactions underlying this disease process can aid
      identification of novel treatment targets. Here, we found a lowered threshold for
      stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian
      Preferring (msP) rats genetically selected for high alcohol preference. In situ
      hybridization for a panel of 20 stress-related genes in 16 brain regions was used
      to screen for differential gene expression that may underlie this behavioral
      phenotype. An innate up-regulation of the Crhr1 transcript, encoding the
      corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic
      brain areas of msP rats genetically selected for high alcohol preference, was
      associated with genetic polymorphism of the Crhr1 promoter, and was accompanied
      by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10-20
      mg/kg) was devoid of effects on operant alcohol self-administration in unselected
      Wistar rats but significantly suppressed this behavior in the msP line. Stress
      induced reinstatement of alcohol seeking was not significantly affected by
      antalarmin in Wistar rats but was fully blocked in msP animals. These data
      demonstrate that Crhr1 genotype and expression interact with environmental stress
      to reinstate alcohol-seeking behavior.

PMID- 17015826
TI  - The history of early bee diversification based on five genes plus morphology.
AB  - Bees, the largest (>16,000 species) and most important radiation of pollinating
      insects, originated in early to mid-Cretaceous, roughly in synchrony with the
      angiosperms (flowering plants). Understanding the diversification of the bees and
      the coevolutionary history of bees and angiosperms requires a well supported
      phylogeny of bees (as well as angiosperms). We reconstructed a robust phylogeny
      of bees at the family and subfamily levels using a data set of five genes (4,299
      nucleotide sites) plus morphology (109 characters). The molecular data set
      included protein coding (elongation factor-1alpha, RNA polymerase II, and LW
      rhodopsin), as well as ribosomal (28S and 18S) nuclear gene data. Analyses of
      both the DNA data set and the DNA+morphology data set by parsimony and Bayesian
      methods yielded a single well supported family-level tree topology that places
      Melittidae as a paraphyletic group at the base of the phylogeny of bees. This
      topology ("Melittidae-LT basal") is significantly better than a previously
      proposed alternative topology ("Colletidae basal") based both on likelihood and
      Bayesian methods. Our results have important implications for understanding the
      early diversification, historical biogeography, host-plant evolution, and fossil
      record of bees. The earliest branches of bee phylogeny include lineages that are
      predominantly host-plant specialists, suggesting that host-plant specificity is
      an ancestral trait in bees. Our results suggest an African origin for bees,
      because the earliest branches of the tree include predominantly African lineages.
      These results also help explain the predominance of Melittidae, Apidae, and
      Megachilidae among the earliest fossil bees.

PMID- 17015827
TI  - A nucleobase lesion remodels the interaction of its normal neighbor in a DNA
      glycosylase complex.
AB  - How DNA glycosylases search through millions of base pairs and discriminate
      between rare sites of damage and otherwise undamaged bases is poorly understood.
      Even less understood are the details of the structural states arising from DNA
      glycosylases interacting with undamaged DNA. Recognizing the mutagenic lesion 7,8
      dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable
      challenge, because this oxidized nucleobase differs by only two atoms from its
      normal counterpart, guanine (G), and buried in the structure of naked B-form DNA,
      oxoG and G are practically indistinguishable from each other. We have used
      disulfide cross-linking technology to capture a human oxoG repair protein, 8
      oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair located
      adjacent to an oxoG:C base pair in DNA. The x-ray structure of the trapped
      complex reveals that the presence of the 8-oxoG drastically changes the local
      conformation of the extruded G. The extruded but intrahelical state of the G in
      this structure offers a view of an early intermediate in the base-extrusion
      pathway.

PMID- 17015828
TI  - TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic
      leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the
      accrual of genetic rearrangements and/or mutations within the dominant clone. The
      TEL-AML1 (ETV6-RUNX1) fusion in precursor-B (pre-B) ALL is the most common
      genetic rearrangement in childhood cancer; however, the cellular origin and the
      molecular pathogenesis of TEL-AML1-induced leukemia have not been identified. To
      study the origin of TEL-AML1-induced ALL, we generated transgenic zebrafish
      expressing TEL-AML1 either ubiquitously or in lymphoid progenitors. TEL-AML1
      expression in all lineages, but not lymphoid-restricted expression, led to
      progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of
      the transgenic zebrafish. This leukemia was transplantable to conditioned wild
      type recipients. We demonstrate that TEL-AML1 induces a B cell differentiation
      arrest, and that leukemia development is associated with loss of TEL expression
      and elevated Bcl2/Bax ratio. The TEL-AML1 transgenic zebrafish models human pre-B
      ALL, identifies the molecular pathways associated with leukemia development, and
      serves as the foundation for subsequent genetic screens to identify modifiers and
      leukemia therapeutic targets.

PMID- 17015829
TI  - Slow progressive degeneration of nigral dopaminergic neurons in postnatal
      Engrailed mutant mice.
AB  - The homeobox transcription factors Engrailed-1 and Engrailed-2 are required for
      the survival of mesencephalic dopaminergic neurons in a cell-autonomous and gene
      dose-dependent manner. Because of this requirement, the cells die by apoptosis
      when all four alleles of the Engrailed genes are genetically ablated (En1-/-;En2
      /-). In the present study, we show that viable and fertile mice, heterozygous
      null for Engrailed-1 and homozygous null for Engrailed-2 (En1+/-;En2-/-), have an
      adult phenotype that resembles key pathological features of Parkinson's disease.
      Specifically, postnatal mutant mice exhibit a progressive degeneration of
      dopaminergic neurons in the substantia nigra during the first 3 mo of their
      lives, leading to diminished storage and release of dopamine in the caudate
      putamen, motor deficits similar to akinesia and bradykinesia, and a lower body
      weight. This genetic model may provide access to the molecular etiology for
      Parkinson's disease and could assist in the development of novel treatments for
      this neurodegenerative disorder.

PMID- 17015830
TI  - Selective fluorescent imaging of superoxide in vivo using ethidium-based probes.
AB  - The putative oxidation of hydroethidine (HE) has become a widely used fluorescent
      assay for the detection of superoxide in cultured cells. By covalently joining HE
      to a hexyl triphenylphosphonium cation (Mito-HE), the HE moiety can be targeted
      to mitochondria. However, the specificity of HE and Mito-HE for superoxide in
      vivo is limited by autooxidation as well as by nonsuperoxide-dependent cellular
      processes that can oxidize HE probes to ethidium (Etd). Recently, superoxide was
      shown to react with HE to generate 2-hydroxyethidium [Zhao, H., Kalivendi, S.,
      Zhang, H., Joseph, J., Nithipatikom, K., Vasquez-Vivar, J. & Kalyanaraman, B.
      (2003) Free Radic. Biol. Med. 34, 1359-1368]. However, 2-hydroxyethidium is
      difficult to distinguish from Etd by conventional fluorescence techniques
      exciting at 510 nm. While investigating the oxidation of Mito-HE by superoxide,
      we found that the superoxide product of both HE and Mito-HE could be selectively
      excited at 396 nm with minimal interference from other nonspecific oxidation
      products. The oxidation of Mito-HE monitored at 396 nm by antimycin-stimulated
      mitochondria was 30% slower than at 510 nm, indicating that superoxide production
      may be overestimated at 510 nm by even a traditional superoxide-stimulating
      mitochondrial inhibitor. The rate-limiting step for oxidation by superoxide was
      4x10(6) M-1.s-1, which is proposed to involve the formation of a radical from
      Mito-HE. The rapid reaction with a second superoxide anion through radical
      radical coupling may explain how Mito-HE and HE can compete for superoxide in
      vivo with intracellular superoxide dismutases. Monitoring oxidation at both 396
      and 510 nm of excitation wavelengths can facilitate the more selective detection
      of superoxide in vivo.

PMID- 17015831
TI  - Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1
      in the striatum.
AB  - Much research has implicated the striatum in motor learning, but the underlying
      mechanisms have not been identified. Although NMDA receptor (NMDAR)-dependent
      long-term potentiation has been observed in the striatum, its involvement in
      motor learning remains unclear. To examine the role of striatal NMDAR in motor
      learning, we created striatum-specific NMDAR1 subunit knockout mice, analyzed the
      striatal anatomy and neuronal morphology of these mice, evaluated their
      performance on well established motor tasks, and performed electrophysiological
      recordings to assay striatal NMDAR function and long-term synaptic plasticity.
      Our results show that deleting the NMDAR1 subunit of the NMDAR specifically in
      the striatum, which virtually abolished NMDAR-mediated currents, resulted in only
      small changes in striatal neuronal morphology but severely impaired motor
      learning and disrupted dorsal striatal long-term potentiation and ventral
      striatal long-term depression.

PMID- 17015832
TI  - Evolution of sensory complexity recorded in a myxobacterial genome.
AB  - Myxobacteria are single-celled, but social, eubacterial predators. Upon
      starvation they build multicellular fruiting bodies using a developmental program
      that progressively changes the pattern of cell movement and the repertoire of
      genes expressed. Development terminates with spore differentiation and is
      coordinated by both diffusible and cell-bound signals. The growth and development
      of Myxococcus xanthus is regulated by the integration of multiple signals from
      outside the cells with physiological signals from within. A collection of M.
      xanthus cells behaves, in many respects, like a multicellular organism. For these
      reasons M. xanthus offers unparalleled access to a regulatory network that
      controls development and that organizes cell movement on surfaces. The genome of
      M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta
      proteobacteria. We suggest that gene duplication and divergence were major
      contributors to genomic expansion from its progenitor. More than 1,500
      duplications specific to the myxobacterial lineage were identified, representing
      >15% of the total genes. Genes were not duplicated at random; rather, genes for
      cell-cell signaling, small molecule sensing, and integrative transcription
      control were amplified selectively. Families of genes encoding the production of
      secondary metabolites are overrepresented in the genome but may have been
      received by horizontal gene transfer and are likely to be important for
      predation.

PMID- 17015833
TI  - A role for WRN in telomere-based DNA damage responses.
AB  - Telomeres cap the ends of eukaryotic chromosomes and prevent them from being
      recognized as DNA breaks. We have shown that certain DNA damage responses induced
      during senescence and, at times of telomere uncapping, also can be induced by
      treatment of cells with small DNA oligonucleotides homologous to the telomere 3'
      single-strand overhang (T-oligos), implicating this overhang in generation of
      these telomere-based damage responses. Here, we show that T-oligo-treated
      fibroblasts contain gammaH2AX foci and that these foci colocalize with telomeres.
      T-oligos with nuclease-resistant 3' ends are inactive, suggesting that a nuclease
      initiates T-oligo responses. We therefore examined WRN, a 3'-->5' exonuclease and
      helicase mutated in Werner syndrome, a disorder characterized by aberrant
      telomere maintenance, premature aging, chromosomal rearrangements, and
      predisposition to malignancy. Normal fibroblasts and U20S osteosarcoma cells
      rendered deficient in WRN showed reduced phosphorylation of p53 and histone H2AX
      in response to T-oligo treatment. Together, these data demonstrate a role for WRN
      in processing of telomeric DNA and subsequent activation of DNA damage responses.
      The T-oligo model helps define the role of WRN in telomere maintenance and
      initiation of DNA damage responses after telomere disruption.

PMID- 17015834
TI  - DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the
      antioxidant transcriptional master regulator Nrf2.
AB  - DJ-1/PARK7, a cancer- and Parkinson's disease (PD)-associated protein, protects
      cells from toxic stresses. However, the functional basis of this protection has
      remained elusive. We found that loss of DJ-1 leads to deficits in NQO1 [NAD(P)H
      quinone oxidoreductase 1], a detoxification enzyme. This deficit is attributed to
      a loss of Nrf2 (nuclear factor erythroid 2-related factor), a master regulator of
      antioxidant transcriptional responses. DJ-1 stabilizes Nrf2 by preventing
      association with its inhibitor protein, Keap1, and Nrf2's subsequent
      ubiquitination. Without intact DJ-1, Nrf2 protein is unstable, and
      transcriptional responses are thereby decreased both basally and after induction.
      This effect of DJ-1 on Nrf2 is present in both transformed lines and primary
      cells across human and mouse species. DJ-1's effect on Nrf2 and subsequent
      effects on antioxidant responses may explain how DJ-1 affects the etiology of
      both cancer and PD, which are seemingly disparate disorders. Furthermore, this DJ
      1/Nrf2 functional axis presents a therapeutic target in cancer treatment and
      justifies DJ-1 as a tumor biomarker.

PMID- 17015835
TI  - Allosteric inhibition of Staphylococcus aureus D-alanine:D-alanine ligase
      revealed by crystallographic studies.
AB  - D-alanine:D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall
      biosynthesis and an important target for developing new antibiotics. It catalyzes
      the formation of D-alanine:D-alanine dipeptide, sequentially by using one D
      alanine and one ATP as substrates for the first-half reaction, and a second D
      alanine substrate to complete the reaction. Some gain of function DDl mutants can
      use an alternate second substrate, causing resistance to vancomycin, one of the
      last lines of defense against life-threatening Gram-positive infections. Here, we
      report the crystal structure of Staphylococcus aureus DDl (StaDDl) and its
      cocrystal structures with 3-chloro-2,2-dimethyl-N
      [4(trifluoromethyl)phenyl]propanamide (inhibitor 1) (Ki=4 microM against StaDDl)
      and with ADP, one of the reaction products, at resolutions of 2.0, 2.2, and 2.6
      A, respectively. The overall structure of StaDDl can be divided into three
      distinct domains. The inhibitor binds to a hydrophobic pocket at the interface of
      the first and the third domain. This inhibitor-binding pocket is adjacent to the
      first D-alanine substrate site but does not overlap with any substrate sites. An
      allosteric inhibition mechanism of StaDDl by this compound was proposed. The
      mechanism provides the basis for developing new antibiotics targeting D-alanine:D
      alanine ligase. Because this compound only interacts with residues from the first
      D-alanine site, inhibitors with this binding mode potentially could overcome
      vancomycin resistance.

PMID- 17015836
TI  - Detecting emerging strains of tuberculosis by using spoligotypes.
AB  - The W-Beijing strain of tuberculosis has been identified in many molecular
      epidemiological studies as being particularly prevalent. This identification has
      been made possible through the development of a number of genotyping technologies
      including spoligotyping. Highly prevalent genotypes associated with outbreaks,
      such as the W-Beijing strain, are implicitly regarded as fast spreading. Here we
      present a quantitative method to identify "emerging" strains, those that are
      spreading faster than the background rate inferred from spoligotype data. The
      approach uses information about the mutation process specific to spoligotypes,
      combined with a model of both transmission and mutation. The core principle is
      that if two comparable strains have the same number of isolates, then the strain
      with fewer inferred mutation events must have spread faster if the mutation
      process is common. Applying this method to four different data sets, we find not
      only the W-Beijing strain, but also a number of other strains, to be emerging in
      this sense. Importantly, the strains that are identified as emerging are not
      simply those with the largest number of cases. The use of this method should
      facilitate the targeting of individual genotypes in intervention programs.

PMID- 17015837
TI  - Generation of heavy-chain-only antibodies in mice.
AB  - We have generated transgenic mice containing hybrid llama/human antibody loci
      that contain two llama variable regions and the human D, J, and Cmu and/or Cgamma
      constant regions. Such loci rearrange productively and rescue B cell development
      efficiently without LC rearrangement. Heavy-chain-only antibodies (HCAb) are
      expressed at high levels, provided that the CH1 domain is deleted from the
      constant regions. HCAb production does not require an IgM stage for effective pre
      B cell signaling. Antigen-specific heavy-chain-only IgM or IgGs are produced upon
      immunization. The IgG is dimeric, whereas IgM is multimeric. The chimeric HCAb
      loci are subject to allelic exclusion, but several copies of the transgenic locus
      can be rearranged and expressed successfully on the same allele in the same cell.
      Such cells are not subject to negative selection. The mice produce a full
      antibody repertoire and provide a previously undescribed avenue to produce
      specific human HCAb in the future.

PMID- 17015838
TI  - Structural basis for understanding oncogenic p53 mutations and designing rescue
      drugs.
AB  - The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in
      approximately 50% of human cancers. We have solved high-resolution crystal
      structures of several oncogenic mutants to investigate the structural basis of
      inactivation and provide information for designing drugs that may rescue
      inactivated mutants. We found a variety of structural consequences upon mutation:
      (i) the removal of an essential contact with DNA, (ii) creation of large, water
      accessible crevices or hydrophobic internal cavities with no other structural
      changes but with a large loss of thermodynamic stability, (iii) distortion of the
      DNA-binding surface, and (iv) alterations to surfaces not directly involved in
      DNA binding but involved in domain-domain interactions on binding as a tetramer.
      These findings explain differences in functional properties and associated
      phenotypes (e.g., temperature sensitivity). Some mutants have the potential of
      being rescued by a generic stabilizing drug. In addition, a mutation-induced
      crevice is a potential target site for a mutant-selective stabilizing drug.

PMID- 17015839
TI  - Ultrafast infrared spectroscopy reveals a key step for successful entry into the
      photocycle for photoactive yellow protein.
AB  - Photoactive proteins such as PYP (photoactive yellow protein) are generally
      accepted as model systems for studying protein signal state formation. PYP is a
      blue-light sensor from the bacterium Halorhodospira halophila. The formation of
      PYP's signaling state is initiated by trans-cis isomerization of the p-coumaric
      acid chromophore upon the absorption of light. The quantum yield of signaling
      state formation is approximately 0.3. Using femtosecond visible pump/mid-IR probe
      spectroscopy, we investigated the structure of the very short-lived ground state
      intermediate (GSI) that results from an unsuccessful attempt to enter the
      photocycle. This intermediate and the first stable GSI on pathway into the
      photocycle, I0, both have a mid-IR difference spectrum that is characteristic of
      a cis isomer, but only the I0 intermediate has a chromophore with a broken
      hydrogen bond with the backbone N atom of Cys-69. We suggest, therefore, that
      breaking this hydrogen bond is decisive for a successful entry into the
      photocycle. The chromophore also engages in a hydrogen-bonding network by means
      of its phenolate group with residues Tyr-42 and Glu-46. We have investigated the
      role of this hydrogen bond by exchanging the H bond-donating residue Glu-46 with
      the weaker H bond-donating glutamine (i.e., Gln-46). We have observed that this
      mutant exhibits virtually identical kinetics and product yields as WT PYP, even
      though during the I0-to-I1 transition, on the 800-ps time scale, the hydrogen
      bond of the chromophore with Gln-46 is broken, whereas this hydrogen bond remains
      intact with Glu-46.

PMID- 17015840
TI  - Androgen receptor as a licensing factor for DNA replication in androgen-sensitive
      prostate cancer cells.
AB  - Androgen receptor (AR) protein expression and function are critical for survival
      and proliferation of androgen-sensitive (AS) prostate cancer cells. Besides its
      ability to function as a transcription factor, experimental observations suggest
      that AR becomes a licensing factor for DNA replication in AS prostate cancer
      cells and thus must be degraded during each cell cycle in these cells to allow
      reinitiation of DNA replication in the next cell cycle. This possibility was
      tested by using the AS human prostate cancer cell lines, LNCaP, CWR22Rv1, and
      LAPC-4. These studies demonstrated that AR levels fluctuate both within and
      between various phases of the cell cycle in each of these AS lines. Consistent
      with its licensing ability, AR is degraded during mitosis via a proteasome
      dependent pathway in these AS prostate cancer cells. In contrast, proteasome
      dependent degradation of AR during mitosis is not observed in AR-expressing but
      androgen-insensitive human prostate stromal cells, in which AR does not function
      as a licensing factor for DNA replication. To evaluate mitotic degradation of AR
      in vivo, the same series of human AS prostate cancers growing as xenografts in
      nude mice and malignant tissues obtained directly from prostate cancer patients
      were evaluated by dual Ki-67 and AR immunohistochemistry for AR expression in
      mitosis. These results document that AR is also down-regulated during mitosis in
      vivo. Thus, AS prostate cancer cells do not express AR protein during mitosis,
      either in vitro or in vivo, consistent with AR functioning as a licensing factor
      for DNA replication in AS prostate cancer cells.

PMID- 17015841
TI  - Neuropathy target esterase catalyzes osmoprotective renal synthesis of
      glycerophosphocholine in response to high NaCl.
AB  - Glycerophosphocholine (GPC) is an osmoprotective compatible and counteracting
      organic osmolyte that accumulates in renal inner medullary cells in response to
      high NaCl and urea. We previously found that high NaCl increases GPC in renal
      [Madin-Darby canine kidney (MDCK)] cells. The GPC is derived from
      phosphatidylcholine, catalyzed by a phospholipase that was not identified at that
      time. Neuropathy target esterase (NTE) was recently shown to be a phospholipase B
      that catalyzes production of GPC from phosphatidylcholine. The purpose of the
      present study was to test whether NTE contributes to the high NaCl-induced
      increase of GPC synthesis in renal cells. We find that in mouse inner medullary
      collecting duct cells, high NaCl increases NTE mRNA within 8 h and NTE protein
      within 16 h. Diisopropyl fluorophosphate, which inhibits NTE esterase activity,
      reduces GPC accumulation, as does an siRNA that specifically reduces NTE protein
      abundance. The 20-h half-life of NTE mRNA is unaffected by high NaCl.
      TonEBP/OREBP is a transcription factor that is activated by high NaCl. Knockdown
      of TonEBP/OREBP by a specific siRNA inhibits the high NaCl-induced increase of
      NTE mRNA. Further, the lower renal inner medullary interstitial NaCl
      concentration that occurs chronically in ClCK1-/- mice and acutely in normal mice
      given furosemide is associated with lower NTE mRNA and protein. We conclude that
      high NaCl increases transcription of NTE, likely mediated by TonEBP/OREBP, and
      that the resultant increase of NTE expression contributes to increased production
      and accumulation of GPC in mammalian renal cells in tissue culture and in vivo.

PMID- 17015842
TI  - Interdigital webbing retention in bat wings illustrates genetic changes
      underlying amniote limb diversification.
AB  - Developmentally regulated programmed cell death sculpts the limbs and other
      embryonic organs in vertebrates. One intriguing example of species-specific
      differences in apoptotic extent is observed in the tissue between the digits. In
      chicks and mice, bone morphogenetic proteins (Bmps) trigger apoptosis of the
      interdigital mesenchyme, leading to freed digits, whereas in ducks, Bmp
      antagonists inhibit the apoptotic program, resulting in webbed feet. Here, we
      show that the phyllostomid bat Carollia perspicillata utilizes a distinct
      mechanism for maintaining interdigit tissue. We find that bat forelimb and
      hindlimb interdigital tissues express Bmp signaling components but that only bat
      hindlimbs undergo interdigital apoptosis. Strikingly, the retention of
      interdigital webbing in the bat forelimb is correlated with a unique pattern of
      Fgf8 expression in addition to the Bmp inhibitor Gremlin. By using a functional
      assay, we show that maintenance of interdigit tissue in the bat wing depends on
      the combined effects of high levels of Fgf signaling and inhibition of Bmp
      signaling. Our data also indicate that although there is not a conserved
      mechanism for maintaining interdigit tissue across amniotes, the expression in
      the bat forelimb interdigits of Gremlin and Fgf8 suggests that these key
      molecular changes contributed to the evolution of the bat wing.

PMID- 17015843
TI  - Culling and cattle controls influence tuberculosis risk for badgers.
AB  - Human and livestock diseases can be difficult to control where infection persists
      in wildlife populations. In Britain, European badgers (Meles meles) are
      implicated in transmitting Mycobacterium bovis, the causative agent of bovine
      tuberculosis (TB), to cattle. Badger culling has therefore been a component of
      British TB control policy for many years. However, large-scale field trials have
      recently shown that badger culling has the capacity to cause both increases and
      decreases in cattle TB incidence. Here, we show that repeated badger culling in
      the same area is associated with increasing prevalence of M. bovis infection in
      badgers, especially where landscape features allow badgers from neighboring land
      to recolonize culled areas. This impact on prevalence in badgers might reduce the
      beneficial effects of culling on cattle TB incidence, and could contribute to the
      detrimental effects that have been observed. Additionally, we show that
      suspension of cattle TB controls during a nationwide epidemic of foot and mouth
      disease, which substantially delayed removal of TB-affected cattle, was
      associated with a widespread increase in the prevalence of M. bovis infection in
      badgers. This pattern suggests that infection may be transmitted from cattle to
      badgers, as well as vice versa. Clearly, disease control measures aimed at either
      host species may have unintended consequences for transmission, both within and
      between species. Our findings highlight the need for policymakers to consider
      multiple transmission routes when managing multihost pathogens.

PMID- 17015845
TI  - Retrieval failure versus memory loss in experimental amnesia: definitions and
      processes.
AB  - For at least 40 years, there has been a recurring argument concerning the nature
      of experimental amnesia, with one side arguing that amnesic treatments interfere
      with the formation of enduring memories and the other side arguing that these
      treatments interfere with the expression of memories that were effectively
      encoded. The argument appears to stem from a combination of (1) unclear
      definitions and (2) real differences in the theoretical vantages that underlie
      the interpretation of relevant data. Here we speak to how the field might avoid
      arguments that are definitional in nature and how various hypotheses fare in
      light of published data. Existing but often overlooked data favor very rapid
      (milliseconds) synaptic consolidation, with experimental amnesia reflecting, at
      least in part, deficits in retrieval rather than in the initial storage of
      information.

PMID- 17015846
TI  - Amnesia or retrieval deficit? Implications of a molecular approach to the
      question of reconsolidation.
AB  - Post-retrieval interference with a memory has uncovered a phenomenon known to the
      field as reconsolidation. In this article, we will review the specific molecular
      mechanisms that have been implicated in reconsolidation. As a result of numerous
      studies over the past five years, it can now be said with a fair amount of
      certainty that reconsolidation is not a recapitulation of the mechanisms
      underlying consolidation, despite what the term "reconsolidation" may suggest.
      Therefore, in addition to reviewing the known mechanisms of reconsolidation, we
      will propose that two experimental approaches involving the targeting of specific
      molecular mechanisms, and the study of these mechanisms during retrieval, may
      serve useful to the field as it is now able to advance beyond comparisons between
      consolidation and reconsolidation.

PMID- 17015847
TI  - The many faces of amnesia.
AB  - Results from studies of retrograde amnesia provide much of the evidence for
      theories of memory consolidation. Retrograde amnesia gradients are often
      interpreted as revealing the time needed for the formation of long-term memories.
      The rapid forgetting observed after many amnestic treatments, including protein
      synthesis inhibitors, and the parallel decay seen in long-term potentiation
      experiments are presumed to reveal the duration of short-term memory processing.
      However, there is clear and consistent evidence that the time courses obtained in
      these amnesia experiments are highly variable within and across experiments and
      treatments. The evidence is inconsistent with identification of basic temporal
      properties of memory consolidation. Alternative views include modulation of
      memory and emphasize the roles that hormones and neurotransmitters have in
      regulating memory formation. Of related interest, converging lines of evidence
      suggest that inhibitors of protein synthesis and of other biochemical processes
      act on modulators of memory formation rather than on mechanisms of memory
      formation. Based on these findings, memory consolidation and reconsolidation
      studies might better be identified as memory modulation and "remodulation"
      studies. Beyond a missing and perhaps unattainable time constant of memory
      consolidation, some current views of memory consolidation assume that memories,
      once formed, are generally unmodifiable. It is this perspective that appears to
      have led to the recent interest in memory reconsolidation. But the view adopted
      here is that memories are continually malleable, being updated by new experiences
      and, at the same time, altering the memories of later experiences. Studies of
      memory remodulation offer promise of understanding the neurobiological bases by
      which new memories are altered by prior experiences and by which old memories are
      altered by new experiences.

PMID- 17015848
TI  - In memory of consolidation.

PMID- 17015849
TI  - Lost forever or temporarily misplaced? The long debate about the nature of memory
      impairment.
AB  - Studies of memory impairment in humans and experimental animals have been
      fundamental to learning about the organization of memory and its cellular and
      molecular substrates. When memory impairment occurs, especially after
      perturbations of the nervous system, the question inevitably arises whether the
      impairment reflects impaired information storage or impaired accessibility. This
      topic has been the subject of considerable commentary and experimental work over
      the years. In this reappraisal, I first consider four broad areas of behavioral
      study from the 1970s and 1980s that led to a dominant and compelling view of
      memory impairment as a deficit of information storage. Second, I identify some
      ambiguities that arise about how the terms "storage" and "retrieval" are applied,
      especially when the evidence is somewhat indirect and based on a behavioral
      psychological level of analysis. I then review neurobiological findings that have
      been largely overlooked in these discussions. The relevant studies are ones where
      it has been possible to monitor neurons and synapses in direct relation to
      behavioral memory, for example, in animals with simple nervous systems and in
      single cell recordings from behaving monkeys. This work provides a
      straightforward and illuminating perspective on the question and confirms the
      view that first emerged from less direct evidence.

PMID- 17015851
TI  - Reconsolidation: a brief history, a retrieval view, and some recent issues.
AB  - This review briefly traces some of the history of the phenomenon of what has come
      to be called "reconsolidation." The early findings of retrograde amnesia for an
      old but reactivated memory led to several interesting but largely behaviorally
      oriented studies. With only a few sporadic exceptions, research in the area
      languished until about 2000, when several articles caught the attention of the
      neuroscience community and led to a number of studies examining the phenomenon at
      several different levels of analysis. We consider several of the current issues
      generated by those studies, present a retrieval based model that may account for
      some findings, and indicate some possible new directions on this topic.

PMID- 17015850
TI  - Fading in.
AB  - Patient H.M. can form new memories and maintain them for a few seconds before
      they fade away. From a neurobiological perspective, this amnesia is usually
      attributed to the absence of memory consolidation, that is, memory storage. An
      alternative view holds that this impairment reflects that the memory is present
      but cannot be retrieved. This debate has been unresolved for decades. Here, we
      will consider some of the arguments that make it so difficult to resolve this
      issue. In addition, some recent work will be discussed that has gone beyond the
      shortcomings of previous experimental approaches to strongly suggest that amnesia
      can be due to a retrieval impairment that can be overcome with a reminder--an
      example of memories fading in. Finally, this review will suggest some strategies
      for resolving this debate.

PMID- 17015853
TI  - Dynamic neuroplasticity and the automation of motivated behavior.

PMID- 17015854
TI  - Divide and conquer: an L-type voltage-gated calcium channel subtype finds a role
      in conditioned fear.

PMID- 17015852
TI  - Retrograde amnesia in patients with hippocampal, medial temporal, temporal lobe,
      or frontal pathology.
AB  - There is considerable controversy concerning the theoretical basis of retrograde
      amnesia (R.A.). In the present paper, we compare medial temporal, medial plus
      lateral temporal, and frontal lesion patients on a new autobiographical memory
      task and measures of the more semantic aspects of memory (famous faces and news
      events). Only those patients with damage extending beyond the medial temporal
      cortex into the lateral temporal regions showed severe impairment on free recall
      remote memory tasks, and this held for both the autobiographical and the more
      semantic memory tests. However, on t-test analysis, the medial temporal group was
      impaired in retrieving recent autobiographical memories. Within the medial
      temporal group, those patients who had combined hippocampal and parahippocampal
      atrophy (H+) on quantified MRI performed somewhat worse on the semantic tasks
      than those with atrophy confined to the hippocampi (H-), but scores were very
      similar on autobiographical episodic recall. Correlational analyses with regional
      MRI volumes showed that lateral temporal volume was correlated significantly with
      performance on all three retrograde amnesia tests. The findings are discussed in
      terms of consolidation, reconsolidation, and multiple trace theory: We suggest
      that a widely distributed network of regions underlies the retrieval of past
      memories, and that the extent of lateral temporal damage appears to be critical
      to the emergence of a severe remote memory impairment.

PMID- 17015855
TI  - The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not
      extinction, of contextually conditioned fear in mice.
AB  - Using pharmacological techniques, it has been demonstrated that both
      consolidation and extinction of Pavlovian fear conditioning are dependent to some
      extent upon L-type voltage-gated calcium channels (LVGCCs). Although these
      studies have successfully implicated LVGCCs in Pavlovian fear conditioning, they
      do not provide information about the specific LVGCC isoform involved. Both of the
      major LVGCC subtypes found in the brain (Cav1.2 and Cav1.3) are targets of the
      pharmacological manipulations used in earlier work. In this study, we used mice
      in which the gene for the pore-forming subunit (alpha1D) Cav1.3 was deleted
      (Cav1.3 knockout mice) to elucidate its contribution to consolidation and
      extinction of conditioned fear. We find that Cav1.3 knockout mice exhibit
      significant impairments in consolidation of contextual fear conditioning.
      However, once sufficiently overtrained, the Cav1.3 knockout mice exhibit rates of
      extinction that are identical to that observed in wild-type mice. We also find
      that Cav1.3 knockout mice perform as well as wild-type mice on the hidden
      platform version of the Morris water maze, suggesting that the consolidation
      deficit in conditioned fear observed in the Cav1.3 knockout mice is not likely
      the result of an inability to encode the context, but may reflect an inability to
      make the association between the context and the unconditioned stimulus.

PMID- 17015856
TI  - Opioid modulation of Fos protein expression and olfactory circuitry plays a
      pivotal role in what neonates remember.
AB  - Paradoxically, fear conditioning (odor-0.5 mA shock) yields a learned odor
      preference in the neonate, presumably due to a unique learning and memory circuit
      that does not include apparent amygdala participation. Post-training opioid
      antagonism with naltrexone (NTX) blocks consolidation of this odor preference and
      instead yields memory of a learned odor aversion. Here we characterize the neural
      circuitry underlying this switch during memory consolidation. Experiment 1
      assessed post-training opioid modulation of Fos protein expression within
      olfactory circuitry (olfactory bulb, piriform cortex, amygdala). Odor-shock
      conditioning with no post-training treatment (odor preference) induced
      significant changes in Fos protein expression in the granule cell layer of the
      olfactory bulb and anterior piriform cortex. Post-training opioid receptor
      antagonism (odor aversion) prevented the learning-induced changes in the anterior
      piriform cortex and also induced significant changes in Fos protein expression in
      the central nucleus of the amygdala. Experiment 2 assessed intra-amygdala opioid
      modulation of neonate memory consolidation. Post-training infusion of NTX within
      the amygdala permitted consolidation of an odor aversion, while vehicle-infused
      pups continued to demonstrate an odor preference. Overall, results demonstrate
      that opioids modulate memory consolidation in the neonate via modulating Fos
      protein expression in olfactory circuitry. Furthermore, these results suggest
      that opioids are instrumental in suppressing neonate fear behavior via modulating
      the amygdala.

PMID- 17015858
TI  - Context and occasion setting in Drosophila visual learning.
AB  - In a permanently changing environment, it is by no means an easy task to
      distinguish potentially important events from negligible ones. Yet, to survive,
      every animal has to continuously face that challenge. How does the brain
      accomplish this feat? Building on previous work in Drosophila melanogaster visual
      learning, we have developed an experimental methodology in which combinations of
      visual stimuli (colors and patterns) can be arranged such that the same stimuli
      can either be directly predictive, indirectly predictive, or nonpredictive of
      punishment. Varying this relationship, we found that wild-type flies can
      establish different memory templates for the same contextual color cues. The
      colors can either leave no trace in the pattern memory template, leading to
      context-independent pattern memory (context generalization), or be learned as a
      higher-order cue indicating the nature of the pattern-heat contingency leading to
      context-dependent memory (occasion setting) or serve as a conditioned stimulus
      predicting the punishment directly (simple conditioning). In transgenic flies
      with compromised mushroom-body function, the sensitivity to these subtle
      variations is altered. Our methodology constitutes a new concept for designing
      learning experiments. Our findings suggest that the insect mushroom bodies
      stabilize visual memories against context changes and are not required for
      cognition-like higher-order learning.

PMID- 17015857
TI  - Dynamic shifts in corticostriatal expression patterns of the immediate early
      genes Homer 1a and Zif268 during early and late phases of instrumental training.
AB  - Adaptive motor actions require prior knowledge of instrumental contingencies.
      With practice, these actions can become highly automatic in nature. However, the
      molecular and anatomical substrates mediating these related forms of learning are
      not understood. In the present study, we used in situ hybridization to measure
      the mRNA levels of two immediate early genes (IEGs) in an instrumental paradigm
      where rats learned to lever-press for food. We report that after three training
      sessions, Homer 1a and Zif268 (an effector and regulatory IEG, respectively) were
      significantly induced within an extensive corticostriatal network relative to
      untrained controls. With extended training (23 sessions), however, a shift in the
      expression patterns of the two genes was evident. Expression of Homer 1a
      (official symbol Homer1) decreased significantly in frontal and cingulate
      cortices, whereas striatal expression was generally maintained. Interestingly,
      Homer 1a expression markedly increased with extensive training in the
      ventrolateral region of the striatum (VLS) relative to early learners, suggesting
      that plasticity in the VLS is required for the efficient production of the
      learned behavior or in habit formation. Zif268 (official symbol Egr1) expression
      generally decreased with extensive training; however, these changes were not
      significant. These results demonstrate for the first time, on a molecular level,
      a dynamic shift in the contribution of corticostriatal systems mediating the
      early acquisition and consolidation of goal-directed responses to those engaged
      after extensive training.

PMID- 17015859
TI  - Different parameters support generalization and discrimination learning in
      Drosophila at the flight simulator.
AB  - We have used a genetically tractable model system, the fruit fly Drosophila
      melanogaster to study the interdependence between sensory processing and
      associative processing on learning performance. We investigated the influence of
      variations in the physical and predictive properties of color stimuli in several
      different operant-conditioning procedures on the subsequent learning performance.
      These procedures included context and stimulus generalization as well as color,
      compound, and conditional discrimination (colors and patterns). A surprisingly
      complex dependence of the learning performance on the colors' physical and
      predictive properties emerged, which was clarified by taking into account the fly
      subjective perception of the color stimuli. Based on estimates of the stimuli's
      color and brightness values, we propose that the different tasks are supported by
      different parameters of the color stimuli; generalization occurs only if the
      chromaticity is sufficiently similar, whereas discrimination learning relies on
      brightness differences.

PMID- 17015861
TI  - Summaries for patients. Decision support in primary care and depression outcomes.

PMID- 17015860
TI  - Effects of emotional arousal on multiple memory systems: evidence from
      declarative and procedural learning.
AB  - Extensive evidence documents emotional modulation of hippocampus-dependent
      declarative memory in humans. However, little is known about the emotional
      modulation of striatum-dependent procedural memory. To address how emotional
      arousal influences declarative and procedural memory, the current study utilized
      (1) a picture recognition and (2) a weather prediction (WP) task (a probabilistic
      classification learning task), which have been shown to rely on hippocampal- and
      striatum-based memory systems, respectively. Observers viewed arousing or neutral
      pictures after (Experiment 1) or during (Experiment 2) WP training trials. A 1-wk
      delayed picture recognition memory test revealed enhanced declarative memory for
      arousing compared with neutral pictures. Arousal during encoding impaired initial
      WP acquisition but did not influence retention when tested after a 1-wk delay.
      Data from a subsequent 3-mo delayed test, however, suggested that arousal during
      acquisition may enhance remote WP retention. These results suggest a potential
      dissociation between how readily emotional arousal influences hippocampus
      dependent and striatum-dependent memory systems in humans.

PMID- 17015862
TI  - Summaries for patients. Medical errors that lead to missed diagnoses in primary
      care.

PMID- 17015863
TI  - Summaries for patients. A comparison of medications used to prevent high-altitude
      pulmonary edema.

PMID- 17015864
TI  - Summaries for patients. Relationship of quality-of-care measures and outcomes for
      patients receiving hemodialysis.

PMID- 17015866
TI  - Missed and delayed diagnoses in the ambulatory setting: a study of closed
      malpractice claims.
AB  - BACKGROUND: Although missed and delayed diagnoses have become an important
      patient safety concern, they remain largely unstudied, especially in the
      outpatient setting. OBJECTIVE: To develop a framework for investigating missed
      and delayed diagnoses, advance understanding of their causes, and identify
      opportunities for prevention. DESIGN: Retrospective review of 307 closed
      malpractice claims in which patients alleged a missed or delayed diagnosis in the
      ambulatory setting. SETTING: 4 malpractice insurance companies. MEASUREMENTS:
      Diagnostic errors associated with adverse outcomes for patients, process
      breakdowns, and contributing factors. RESULTS: A total of 181 claims (59%)
      involved diagnostic errors that harmed patients. Fifty-nine percent (106 of 181)
      of these errors were associated with serious harm, and 30% (55 of 181) resulted
      in death. For 59% (106 of 181) of the errors, cancer was the diagnosis involved,
      chiefly breast (44 claims [24%]) and colorectal (13 claims [7%]) cancer. The most
      common breakdowns in the diagnostic process were failure to order an appropriate
      diagnostic test (100 of 181 [55%]), failure to create a proper follow-up plan (81
      of 181 [45%]), failure to obtain an adequate history or perform an adequate
      physical examination (76 of 181 [42%]), and incorrect interpretation of
      diagnostic tests (67 of 181 [37%]). The leading factors that contributed to the
      errors were failures in judgment (143 of 181 [79%]), vigilance or memory (106 of
      181 [59%]), knowledge (86 of 181 [48%]), patient-related factors (84 of 181
      [46%]), and handoffs (36 of 181 [20%]). The median number of process breakdowns
      and contributing factors per error was 3 for both (interquartile range, 2 to 4).
      LIMITATIONS: Reviewers were not blinded to the litigation outcomes, and the
      reliability of the error determination was moderate. CONCLUSIONS: Diagnostic
      errors that harm patients are typically the result of multiple breakdowns and
      individual and system factors. Awareness of the most common types of breakdowns
      and factors could help efforts to identify and prioritize strategies to prevent
      diagnostic errors.

PMID- 17015865
TI  - Depression decision support in primary care: a cluster randomized trial.
AB  - BACKGROUND: Intensive collaborative interventions improve depression outcomes,
      but the benefit of less intensive interventions is not clear. OBJECTIVE: To
      determine whether decision support improves outcomes for patients with
      depression. DESIGN: Clinician-level, cluster randomized, controlled trial.
      SETTING: 5 primary care clinics of 1 Veterans Affairs medical center.
      PARTICIPANTS: 41 primary care clinicians, and 375 patients with depression
      (Patient Health Questionnaire [PHQ-9] depression scores of 10 to 25 or Hopkins
      Symptom Checklist-20 [SCL-20] scores > or = 1.0). MEASUREMENTS: The primary
      outcome was change in depression score (SCL-20) at 6 and 12 months. Secondary
      outcomes were health-related quality-of-life (36-item Short Form for Veterans [SF
      36V] score), patient satisfaction, antidepressant use, and health care
      utilization. INTERVENTION: Clinicians received depression education and were
      randomly assigned to depression decision support or usual care. The depression
      decision support team, which consisted of a psychiatrist and nurse, provided 1
      early patient educational contact and depression monitoring with feedback to
      clinicians over 12 months. RESULTS: Although SCL-20 depression scores improved in
      both groups, the intervention had no effect compared with usual care. The
      difference in slopes comparing intervention and control over 12 months was 0.20
      (95% CI, -0.37 to 0.78; P = 0.49), which was neither clinically nor statistically
      significant. Changes in SF-36V scores also did not differ between groups. At 12
      months, intervention patients reported greater satisfaction (P = 0.002) and were
      more likely to have had at least 1 mental health specialty appointment (41.1% vs.
      27.2%; P = 0.025), to have received any antidepressant (79.3% vs. 69.3%; P =
      0.041), and to have received antidepressants for 90 days or more (76.2% vs.
      61.6%; P = 0.008). LIMITATIONS: Usual care clinicians received depression
      education and had on-site mental health support, which may have mitigated
      intervention effectiveness. CONCLUSIONS: Decision support improved processes of
      care but not depression outcomes. More intensive care management or specialty
      treatment may be needed to improve depression outcomes.

PMID- 17015867
TI  - Both tadalafil and dexamethasone may reduce the incidence of high-altitude
      pulmonary edema: a randomized trial.
AB  - BACKGROUND: High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic
      pulmonary vasoconstriction associated with decreased bioavailability of nitric
      oxide in the lungs and by impaired reabsorption of alveolar fluid. OBJECTIVE: To
      investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and
      acute mountain sickness (AMS) in adults with a history of HAPE. DESIGN:
      Randomized, double-blind, placebo-controlled study performed in summer 2003.
      SETTING: Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m.
      PATIENTS: 29 adults with previous HAPE. INTERVENTION: Prophylactic tadalafil (10
      mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559
      m. MEASUREMENTS: Chest radiography was used to diagnose HAPE. A Lake Louise score
      greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by
      using Doppler echocardiography, and nasal potentials were measured as a surrogate
      marker of alveolar sodium transport. RESULTS: Two participants who received
      tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study;
      they did not have HAPE at that time. High-altitude pulmonary edema developed in 7
      of 9 participants receiving placebo and 1 of the remaining 8 participants
      receiving tadalafil but in none of the 10 participants receiving dexamethasone (P
      = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo).
      Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of
      10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020
      for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery
      pressure increased less in participants receiving dexamethasone (16 mm Hg [95%
      CI, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [CI, 6 to 20 mm Hg]) than in those
      receiving placebo (28 mm Hg [CI, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs.
      placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant
      difference between groups was found in change in nasal potentials and expression
      of leukocyte sodium transport protein messenger RNA. LIMITATIONS: The study
      involved a small sample of adults with a history of HAPE. CONCLUSIONS: Both
      dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may
      reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone
      prophylaxis may also reduce the incidence of AMS in these adults.
      ClinicalTrials.gov identifier: NCT00274430.

PMID- 17015868
TI  - Brief communication: Cardiovascular screening practices of major North American
      professional sports teams.
AB  - BACKGROUND: Customary preparticipation screening strategies to detect heart
      disease in professional athletes have not been examined systematically.
      OBJECTIVE: To describe the current preparticipation cardiovascular screening
      process for professional athletes. DESIGN: Screening practices surveyed by
      questionnaire. SETTING: The 122 major professional sports teams in North America.
      PARTICIPANTS: Athletic trainers and team physicians. MEASUREMENTS: League
      recommendations for history taking and physical examination and noninvasive
      testing were compared with screening recommendations from an American Heart
      Association consensus panel. RESULTS: All 122 teams have team physicians perform
      annual screening, including family and personal history taking (100%), physical
      examination (100%), and lipid panels (108 of 122 [89%]). Diagnostic testing by
      using electrocardiography was substantially more common (112 of 122 [92%]) than
      exercise testing and stress echocardiography (21 of 122 [17%]) or
      echocardiography (16 of 122 [13%]). League recommendations for history taking and
      physical examination were most complete for Major League Baseball and the
      National Hockey League, meeting 10 of 12 and 8 of 12 American Heart Association
      recommendations, respectively. The most comprehensive cardiovascular screening
      using echocardiography is confined to selected, elite professional basketball
      players. LIMITATIONS: Data were self-reported by team representatives.
      CONCLUSIONS: A variety of nonstandardized preparticipation screening strategies
      for the detection of cardiovascular disease, varying considerably in scope,
      constitute customary practice among professional sports teams.

PMID- 17015869
TI  - Relationship between clinical performance measures and outcomes among patients
      receiving long-term hemodialysis.
AB  - BACKGROUND: Patients receiving long-term hemodialysis have a yearly mortality
      rate of 15% to 20%. OBJECTIVE: To determine whether attaining clinical
      performance measures for hemodialysis care is associated with favorable 12-month
      mortality and hospitalization rates. DESIGN: Cohort study. SETTING: Outpatient
      hemodialysis centers in the United States. PATIENTS: 15 287 patients who were
      selected from a 5% random sample of patients receiving long-term hemodialysis.
      MEASUREMENTS: The authors used data from the Centers for Medicare & Medicaid
      Services End-Stage Renal Disease Clinical Performance Measures Project from 1999
      and 2000. The clinical performance measure targets were hemoglobin value of 110
      g/L or greater; serum albumin value of 40 g/L or greater or 37 g/L or greater
      (bromcresol green and bromcresol purple laboratory methods, respectively); use of
      a fistula for vascular access; and measured single-pool Kt/V urea value of 1.2 or
      greater. The outcome measures were death or hospitalization during 1-year follow
      up. RESULTS: 8364 patients (54.7%) were hospitalized and 3062 (20.0%) died during
      the 12-month follow-up period. Six percent of patients did not meet any clinical
      measure targets, 24% met 1 target, 39% met 2 targets, 24% met 3 targets, and 7%
      met all 4 targets. The unadjusted 12-month hospitalization and mortality rates
      for these 5 groups were 60%, 60%, 56%, 49%, and 43% (P < 0.001) and 29%, 25%,
      21%, 14%, and 7% (P < 0.001), respectively. The risk for death increased for each
      additional guideline indicator that was not met: Adjusted hazard ratios were 4.6
      (95% CI, 3.3 to 6.4), 3.5 (CI, 2.6 to 4.7), 2.6 (CI, 1.9 to 3.5), and 1.9 (CI,
      1.4 to 2.6) for 0, 1, 2, or 3 targets met, respectively, compared with meeting 4
      targets (referent). Similarly, the risk for hospitalization increased for each
      additional guideline indicator that was not met: Adjusted hazard ratios were 1.6
      (CI, 1.4 to 1.9), 1.5 (CI, 1.3 to 1.7), 1.3 (CI, 1.1 to 1.5), and 1.1 (CI, 0.98
      to 1.3), respectively. LIMITATIONS: It was not possible to determine the roles of
      severity of illness, other patient factors, or suboptimal care in failure to meet
      performance measures. CONCLUSIONS: In patients receiving long-term hemodialysis,
      meeting multiple clinical measure targets is associated with a decrease in
      hospitalization and mortality rates.

PMID- 17015870
TI  - Narrative review: lack of evidence for recommended low-density lipoprotein
      treatment targets: a solvable problem.
AB  - Recent national recommendations have proposed that physicians should titrate
      lipid therapy to achieve low-density lipoprotein (LDL) cholesterol levels less
      than 1.81 mmol/L (<70 mg/dL) for patients at very high cardiovascular risk and
      less than 2.59 mmol/L (<100 mg/dL) for patients at high cardiovascular risk. To
      examine the clinical evidence for these recommendations, the authors sought to
      review all controlled trials, cohort studies, and case-control studies that
      examined the independent relationship between LDL cholesterol and major
      cardiovascular outcomes in patients with LDL cholesterol levels less than 3.36
      mmol/L (<130 mg/dL). For those with LDL cholesterol levels less than 3.36 mmol/L
      (<130 mg/dL), the authors found no clinical trial subgroup analyses or valid
      cohort or case-control analyses suggesting that the degree to which LDL
      cholesterol responds to a statin independently predicts the degree of
      cardiovascular risk reduction. Published studies had avoidable limitations, such
      as a reliance on ecological (aggregate) analyses, use of analyses that ignore
      statins' other proposed mechanisms of action, and failure to account for known
      confounders (especially healthy volunteer effects). Clear, compelling evidence
      supports near-universal empirical statin therapy in patients at high
      cardiovascular risk (regardless of their natural LDL cholesterol values), but
      current clinical evidence does not demonstrate that titrating lipid therapy to
      achieve proposed low LDL cholesterol levels is beneficial or safe.

PMID- 17015871
TI  - Narrative review: Electrocution and life-threatening electrical injuries.
AB  - The authors reviewed the mechanisms and pathophysiology of typically encountered
      electrical injuries by searching English-language publications listed in MEDLINE
      and reference lists from identified articles. They included relevant
      retrospective studies, case reports, and review articles published between 1966
      and 2005. The authors also searched the Internet for information related to
      electrocution and life-threatening electrical injuries. They found that
      familiarity with basic principles of physics elucidates the typical injuries
      sustained by patients who experience electrical shock. Death due to electrocution
      occurs frequently. However, patients successfully resuscitated after
      cardiopulmonary arrest often have a favorable prognosis. Approximately 3000
      patients who survive electrical shock are admitted to specialized burn units
      annually. Patients with serious electrical burns admitted to the intensive care
      unit are trauma patients and should be treated accordingly. Initial prediction of
      outcome for patients who have experienced electrical shock is difficult, as the
      full degree of injury is often not apparent.

PMID- 17015872
TI  - Update in geriatrics.

PMID- 17015873
TI  - Improving care for depression: there's no free lunch.

PMID- 17015874
TI  - Is ambulatory patient safety just like hospital safety, only without the "stat"?

PMID- 17015875
TI  - Hypoxic lung whiteout: further clearing but more questions from on high.

PMID- 17015876
TI  - Adiposity of the heart.

PMID- 17015878
TI  - Risk assessment for and strategies to reduce perioperative pulmonary
      complications.

PMID- 17015879
TI  - Adiposity of the heart.

PMID- 17015880
TI  - Adiposity of the heart.

PMID- 17015881
TI  - Adiposity of the heart.

PMID- 17015882
TI  - Diabetic muscle infarction mistaken for infectious cellulitis.

PMID- 17015884
TI  - Impact on survival of time from definitive surgery to initiation of adjuvant
      chemotherapy for early-stage breast cancer.
AB  - PURPOSE: To determine if time to start of adjuvant chemotherapy after curative
      surgery influences survival in early-stage breast cancer. PATIENTS AND METHODS: A
      retrospective review was conducted of 2,594 patients receiving adjuvant
      chemotherapy for stage I and II breast cancer between 1989 and 1998 at the
      British Columbia Cancer Agency. Relapse-free survival (RFS) and overall survival
      (OS) were compared among patients grouped by time from definitive curative
      surgery to start of adjuvant chemotherapy (< or = 4 weeks, > 4 to 8 weeks, > 8 to
      12 weeks, and >12 to 24 weeks). RESULTS: RFS and OS were similar for women
      starting chemotherapy up to 12 weeks after surgery. OS hazard ratio (univariate)
      for initiation of chemotherapy more than 12 weeks compared with 12 weeks or less
      after surgery was 1.5 (95% CI, 1.07 to 2.10; P = .017). Five-year OS rates were
      84%, 85%, 89%, and 78%, (log-rank P = .013); RFS rates were 74%, 79%, 82%, and
      69% (log-rank P = .004) for patients starting chemotherapy 4 weeks or fewer, more
      than 4 to 8 weeks, more than 8 to 12 weeks, and more than 12 to 24 weeks after
      surgery, respectively. In multivariate analysis, independent prognostic factors
      were grade, size, nodal status, estrogen receptor, age, and lymphatic and/or
      vascular invasion. Initiation of adjuvant chemotherapy more than 12 weeks from
      surgery remained significantly associated with inferior survival, with a hazard
      ratio of 1.6 (95% CI, 1.2 to 2.3; P = .005). CONCLUSION: This retrospective
      analysis suggests that adjuvant chemotherapy is equally effective up to 12 weeks
      after definitive surgery but that RFS and OS appear to be compromised by delays
      of more than 12 weeks after definitive surgery.

PMID- 17015885
TI  - Metabolism of phytol to phytanic acid in the mouse, and the role of PPARalpha in
      its regulation.
AB  - Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of
      phytanic and pristanic acid, branched-chain fatty acids that are both ligands for
      the nuclear hormone receptor peroxisome proliferator-activated receptor alpha
      (PPARalpha). To investigate the metabolism of phytol and the role of PPARalpha in
      its regulation, wild-type and PPARalpha knockout (PPARalpha-/-) mice were fed a
      phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a
      synthetic PPARalpha agonist. After the phytol-enriched diet, phytol could only be
      detected in small intestine, the site of uptake, and liver. Upon longer duration
      of the diet, the level of the (E)-isomer of phytol increased significantly in the
      liver of PPARalpha-/- mice compared with wild-type mice. Activity measurements of
      the enzymes involved in phytol metabolism showed that treatment with a PPARalpha
      agonist resulted in a PPARalpha-dependent induction of at least two steps of the
      phytol degradation pathway in liver. Furthermore, the enzymes involved showed a
      higher activity toward the (E)-isomer than the (Z)-isomer of their respective
      substrates, indicating a stereospecificity toward the metabolism of (E)-phytol.
      In conclusion, the results described here show that the conversion of phytol to
      phytanic acid is regulated via PPARalpha and is specific for the breakdown of (E)
      phytol.

PMID- 17015886
TI  - Electronegative LDLs from familial hypercholesterolemic patients are
      physicochemically heterogeneous but uniformly proapoptotic.
AB  - A highly electronegative fraction of human plasma LDLs, designated L5, has
      distinctive biological activity that includes induction of apoptosis in bovine
      aortic endothelial cells (BAECs). This study was performed to identify a
      relationship between LDL density, electronegativity, and biological activity,
      namely, the induction of apoptosis in BAECs. Plasma LDLs from normolipidemic
      subjects and homozygotic familial hypercholesterolemia subjects were separated
      into five subfractions, with increasing electronegativity from L1 to L5, and into
      seven subfractions according to increasing density, D1 to D7. L1 to L5 were also
      separated according to density, and D1 to D7 were separated according to charge.
      The density profiles of L1 to L5 were similar (maximum density = 1.030 +/- 0.002
      g/ml). Induction of apoptosis by all seven density subfractions was confined to
      the highly electronegative fraction, L5, and within each density subfraction the
      magnitude of apoptosis correlated with the L5 content. Electronegative LDL is
      heterogeneous with respect to density and composition, and induction of apoptosis
      is more strongly associated with LDL electronegativity than with LDL size or
      density.

PMID- 17015887
TI  - A perspective on post-Chernobyl radioablation in young females.

PMID- 17015888
TI  - Extent of viability to predict response to cardiac resynchronization therapy in
      ischemic heart failure patients.
AB  - The response to cardiac resynchronization therapy (CRT) varies significantly
      among individuals. Preliminary data suggest that the presence of myocardial
      viability may be important for response to CRT. The aim of this study was to
      evaluate whether the extent of viability could predict response to CRT after 6
      mo. METHODS: Sixty-one consecutive patients with advanced heart failure, left
      ventricular ejection fraction < 35%, QRS duration > 120 ms, and chronic coronary
      artery disease were included. To determine the extent of viability all patients
      underwent nuclear imaging with 18F-FDG SPECT before implantation. Clinical and
      echocardiographic parameters were assessed at baseline and after 6 mo of follow
      up. RESULTS: The presence of myocardial viability was directly related to an
      increase in left ventricular ejection fraction after 6 mo of CRT. Furthermore,
      the extent of viability in responders (n = 38) was significantly larger compared
      with that of nonresponders (n = 23; 12 +/- 3 vs. 7 +/- 3 viable segments, P <
      0.01). Moreover, the optimal cutoff value to predict clinical response to CRT was
      identified at an extent of 11 viable segments or more (in a 17-segment model),
      yielding a sensitivity of 74% and a specificity of 87%. CONCLUSION: The presence
      of myocardial viability is directly related to response to CRT in patients with
      ischemic heart failure. Interestingly, using a cutoff level of 11 viable segments
      or more, the extent of viability could be used to predict response. Therefore,
      evaluation for myocardial viability may be considered in the selection process
      for CRT.

PMID- 17015889
TI  - Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with
      sarcoidosis.
AB  - 67Ga scintigraphy has been used for years in sarcoidosis for diagnosis and the
      extent of the disease. However, little information is available on the comparison
      of 18F-FDG PET and 67Ga scintigraphy in the assessment of sarcoidosis. The
      purpose of this study was to compare the uptake of 18F-FDG and 67Ga in the
      evaluation of pulmonary and extrapulmonary involvement in patients with
      sarcoidosis. METHODS: Eighteen patients with sarcoidosis were examined. 18F-FDG
      PET was performed at 1 h after injection of 185-200 MBq 18F-FDG. 67Ga whole-body
      planar and thoracic SPECT images were acquired 72 h after injection of 111 MBq
      67Ga. We evaluated 18F-FDG and 67Ga uptake visually and semiquantitatively using
      standardized uptake values (SUVs) and the ratio of lesion to normal lumbar spine
      (L/N ratio), respectively. The presence of pulmonary and extrapulmonary lesions
      was evaluated histopathologically or by the radiologic findings. RESULTS: Five
      patients had only pulmonary lesions, 12 patients had both pulmonary and
      extrapulmonary lesions, and 1 patient had only an extrapulmonary lesion. Both
      67Ga planar and SPECT images detected 17 of 21 (81%) clinically observed
      pulmonary sites. The mean +/- SD of the L/N ratio was 1.97 +/- 1.09. 67Ga planar
      images detected 15 of 31 (48%) clinically observed extrapulmonary sites. The mean
      +/- SD of the L/N ratio was 1.17 +/- 0.33. 18F-FDG PET detected all 21 (100%)
      clinically observed pulmonary sites. The mean +/- SD of the SUV was 7.40 +/-
      2.48. 18F-FDG PET detected 28 of 31 (90%) clinically observed extrapulmonary
      sites. The mean +/- SD of the SUV was 5.90 +/- 2.75. CONCLUSION: The results of
      this clinical study suggest that 18F-FDG PET can detect pulmonary lesions to a
      similar degree as 67Ga scintigraphy. However, 18F-FDG PET appears to be more
      accurate and contributes to a better evaluation of extrapulmonary involvement in
      sarcoidosis patients.

PMID- 17015890
TI  - Bone scintigraphy predicts outcome of steroid injection for plantar fasciitis.
AB  - Plantar fasciitis is a common cause of foot pain and may be disabling. Although
      localized injection is painful, anesthetics or corticosteroids can relieve
      symptoms well. Bone scintigraphy can confirm the diagnosis. We hypothesized that
      blood-pool abnormalities could provide prognostic information on the response to
      such injections. METHODS: We devised scintigraphic criteria that graded the blood
      pool abnormalities as being localized to the plantar enthesis, being localized to
      half the length of the aponeurosis, or involving the whole aponeurosis. We
      evaluated 24 patients with an established diagnosis of plantar fasciitis, 8 of
      whom had bilateral disease, leading to a total of 32 feet injected. RESULTS:
      After injection, pain was relieved either completely or nearly completely in 20
      feet. The other 12 feet had short-term or no improvement, with persistent pain
      and loss of function at 4-5 wk after injection. Of the 20 feet responding to
      injection, 14 had focal hyperemia on blood-pool images and 6 had minimal
      extension into the proximal third of the plantar soft tissues. No patient with
      diffuse hyperemia in the plantar fascia had a response (5/12 feet). On the
      delayed images of the 20 responders, mild inferior calcaneal uptake was seen in 8
      feet, moderate uptake in 6, and severe uptake in 6. These groups did not
      significantly differ (P > 0.05). The blood-pool studies had good reproducibility,
      with a kappa-value of 0.64. CONCLUSION: Critical evaluation of plantar blood-pool
      images provides prognostic information on the response to localized injection
      into the enthesis. Reporting such studies is simple and reproducible.

PMID- 17015891
TI  - Diagnosis of misery perfusion using noninvasive 15O-gas PET.
AB  - To avoid arterial blood sampling and complicated analyses in 15O-gas PET studies,
      we evaluated a noninvasive technique using the count-based method for measuring
      asymmetric increases in oxygen extraction fraction (OEF) in cerebrovascular
      disease. METHODS: Eighteen patients (mean age +/- SD, 61 +/- 16 y) with
      atherothrombotic large-cerebral-artery disease were studied for the measurement
      of hemodynamic parameters using the 15O-gas steady-state method with inhalation
      of 15O2, C15O2, and C15O. All patients also underwent H2(15)O PET with the bolus
      injection method. Count-based ratio images of 15O2/C15O2 and (15)O2/H2(15)O were
      calculated, and asymmetry indices (AIs) were obtained (cbOEF(SS)-AI and cbOEF(BO)
      AI, respectively) using regions of interest drawn bilaterally on the cerebral
      cortices. These AIs were compared with the AIs of absolute OEF (qOEF-AI) and with
      those after cerebral blood volume (CBV) correction. A contribution factor for
      this correction was defined as a variable alpha, and the effect of the correction
      was evaluated. RESULTS: cbOEF(SS)-AI underestimated qOEF-AI significantly,
      especially with a greater AI (P < 0.05). cbOEF(BO)-AI linearly correlated well
      with qOEF-AI. CBV correction improved the slopes of regression lines between qOEF
      AI and cbOEF(SS)-AI, and the optimal alpha was defined as 0.5. On the other hand,
      cbOEF(BO)-AI fairly estimated qOEF-AI without CBV correction. Correlation between
      qOEF-AI and cbOEF(BO)-AI was adversely affected, and the mean bias was increased,
      with a greater alpha. CONCLUSION: cbOEF(BO)-AI can fairly estimate the AI of OEF
      without CBV correction, whereas cbOEF(SS)-AI might require CBV correction for
      better estimation. The examination time and stress to patients would be reduced
      with the count-based method because it is noninvasive.

PMID- 17015892
TI  - Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated
      activity levels in elderly patients with thyroid cancer.
AB  - Although 131I-iodine (RAI) therapy is a mainstay in the treatment of metastatic
      thyroid cancer, there is controversy regarding the maximum activity that can
      safely be administered without dosimetric determination of the maximum tolerable
      activity (MTA). At most institutions, a fixed empiric dosing strategy is often
      used, with administered activities ranging from 5.55 to 9.25 GBq (150-250 mCi).
      In our experience with dosimetry, we have observed that this empiric dosing
      strategy often results in administered RAI activities exceeding the MTA safety
      limit of 200 cGy (rads) to the blood or bone marrow in many patients with
      metastatic thyroid cancer. METHODS: We retrospectively analyzed 535 hypothyroid
      dosimetry studies performed as part of routine clinical care in 328 patients with
      apparently normal renal function. RESULTS: The MTA was less than 5.18 GBq (140
      mCi) in 3%, less than 7.4 GBq (200 mCi) in 8%, and less than 9.25 GBq (250 mCi)
      in 19%. Analysis of MTA values by age at the time of dosimetry revealed little
      change in the MTA until the age of 70 y, when a significant decrease occurred. An
      empiric administered activity of 7.4 GBq (200 mCi) would exceed the MTA in 8%-15%
      of patients less than 70 y old and 22%-38% of patients 70 y old or older.
      However, administration of 9.25 GBq (250 mCi) would exceed the MTA in 22% of
      patients less than 70 y old and 50% of patients 70 y old or older. Factors
      associated with a lowering of MTA to less than 9.25 GBq (250 mCi) were age at
      dosimetry greater than 45 y, the female sex, subtotal thyroidectomy, and RAI-avid
      diffuse bilateral pulmonary metastases. CONCLUSION: Administered RAI activities
      of less than 5.18 GBq (140 mCi) rarely exposed blood to more than 200 cGy except
      in the very elderly. However, administered activities of 7.4-9.25 GBq (200-250
      mCi) frequently exceeded the calculated MTA in patients 70 y old or older.
      Therefore, dosimetry-guided RAI therapy may be preferable to fixed-dose RAI
      treatment strategies in older patients with thyroid cancer and in patients with
      RAI-avid diffuse bilateral pulmonary metastases, even when renal function is
      normal.

PMID- 17015893
TI  - 18F-FLT PET in hematologic disorders: a novel technique to analyze the bone
      marrow compartment.
AB  - Few diagnostic procedures are available to determine the degree of bone marrow
      cellularity and the numbers of cycling cells in patients with bone marrow
      disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The
      PET tracer 3'-fluoro-3'-deoxy-L-thymidine (18F-FLT) has been developed recently.
      18F-FLT uptake is related to the rate of DNA synthesis and increases with higher
      proliferation rates in many types of cancer. Background uptake of 18F-FLT in bone
      marrow is common. 18F-FLT PET might, therefore, visualize the high cycling
      activity of hematopoietic cells in the bone marrow compartment. Therefore, we
      investigated the feasibility of visualization and quantification of the activity
      of the bone marrow compartment with 18F-FLT PET to distinguish different
      hematologic disorders. METHODS: Clinical and laboratory data of 18 patients with
      myelodysplasia (MDS), chronic myeloproliferative disorders, myelofibrosis,
      aplastic anemia, or multiple myeloma were correlated with the results of 18F-FLT
      PET using visual analysis and the standardized uptake value (SUV). Findings were
      compared with those of healthy control subjects (n = 14). RESULTS: With SUV and
      visual analysis, a distinction could be made between MDS (n = 9), chronic
      myeloproliferative disorders (n = 3), and myelofibrosis (n = 3) compared with
      healthy control subjects. A significant increase in 18F-FLT uptake was observed
      in all of the studied patients with MDS and myeloproliferative disorders. In
      contrast, patients with myelofibrosis and aplastic anemia (n = 1) demonstrated a
      decline in bone marrow 18F-FLT uptake compared with healthy control subjects.
      Comparable results were observed in osteolytic lesions of patients with multiple
      myeloma (n = 2). CONCLUSION: 18F-FLT PET can be used to visualize the
      proliferative activity of the bone marrow compartment and may be helpful to
      distinguish separate hematologic disorders.

PMID- 17015894
TI  - Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with
      paraganglioma, meningioma, small cell lung carcinoma, and melanoma.
AB  - Therapy using the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate
      (177Lu-octreotate) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''
      tetraacetic acid) has been used primarily in gastroenteropancreatic
      neuroendocrine tumors. Here we present the effects of this therapy in a small
      number of patients with metastasized or inoperable paragangliomas, meningiomas,
      small cell lung carcinomas (SCLCs), and melanomas. METHODS: Twelve patients with
      paraganglioma, 5 with meningioma, 3 with SCLC, and 2 with eye melanoma were
      treated. Three meningiomas were very large and exophytic and all standard
      treatments had failed. Patients with melanoma had rapidly progressive disease
      (PD). The intended cumulative dose of 177Lu-octreotate was 22.2-29.6 GBq. Effects
      of the treatment on tumor size were evaluated using the Southwest Oncology Group
      criteria. RESULTS: Two of 4 patients with progressive paraganglioma had tumor
      regression and 1 had stable disease (SD). Of 5 patients with stable
      paraganglioma, 2 had SD, 2 had PD, and in 1 patient treatment outcome could not
      be determined. Paraganglioma was stable in 3 patients in whom the disease status
      at the beginning of therapy was unknown. One of 4 patients with progressive
      meningioma had SD and 3 patients had PD. One patient with stable meningioma at
      the beginning of therapy had SD. All patients with SCLC or melanoma died within 5
      mo after starting therapy because of tumor progression. Although not
      statistically significant, a positive trend was found between high uptake on
      pretherapy somatostatin receptor scintigraphy and treatment outcome. CONCLUSION:
      177Lu-octreotate can be effective in patients with paraganglioma and meningioma.
      Response rates are lower than those in patients with gastroenteropancreatic
      neuroendocrine tumors. Most meningiomas were very large. Further studies are
      needed to confirm the treatment outcome because of the limited number of
      patients. 177Lu-octreotate did not have antitumor effects in patients with small
      lung carcinoma and melanoma.

PMID- 17015895
TI  - Yield of brain 18F-FDG PET in evaluating patients with potentially operable non
      small cell lung cancer.
AB  - The American College of Surgeons Oncology Group recently completed a trial
      evaluating the role of PET with 18F-FDG in patients with documented or suspected
      non-small cell lung cancer. Subjects underwent standard imaging to exclude
      metastatic disease before PET. Here, we report the yield of brain PET in
      evaluating, for potential intracranial metastases, patients who have undergone
      previous brain CT or MRI with negative findings. METHODS: A total of 287
      evaluable patients who had been registered from 22 institutions underwent whole
      body 18F-FDG PET, including dedicated PET of the brain, after routine staging
      procedures had found no suggestion of metastatic disease. Patients were followed
      postoperatively for disease-free and overall survival, with a minimum follow-up
      of 6 mo. Patients with specific brain abnormalities identified by PET were
      further examined, and the findings were evaluated along with the results of CT
      and MRI, clinical management, and follow-up. RESULTS: In 4 patients, PET found
      focal 18F-FDG uptake in the brain suggestive of metastatic disease; however,
      metastatic disease was excluded clinically in all 4 by negative findings on
      further brain imaging. All 4 patients remained alive at follow-up (mean duration,
      10.5 mo; range, 6-16 mo). CONCLUSION: In patients with suspected or proven non
      small cell lung cancer considered resectable by standard imaging, including
      routine preoperative contrast-enhanced CT or MRI of the brain, PET of the brain
      provides no additional information regarding metastatic disease.

PMID- 17015896
TI  - Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas.
AB  - 3'-Deoxy-3'-fluorothymidine (FLT), a thymidine analog, is under investigation for
      monitoring cellular proliferation in gliomas, a potential measure of disease
      progression and response to therapy. Uptake may result from retention in the
      biosynthetic pathway or leakage via the disrupted blood-tumor barrier. Visual
      analysis or static measures of 18F-FLT uptake are problematic as transport and
      retention cannot be distinguished. METHODS: Twelve patients with primary brain
      tumors were imaged for 90 min of dynamic 18F-FLT PET with arterial blood
      sampling. Total blood activity was corrected for labeled metabolites to provide
      an FLT input function. A 2-tissue compartment, 4-rate-constant model was used to
      determine blood-to-tissue transport (K1) and metabolic flux (K(FLT)). Modeling
      results were compared with MR images of blood-brain barrier (BBB) breakdown
      revealed by gadolinium (Gd) contrast enhancement. Parametric image maps of K1 and
      K(FLT) were produced by a mixture analysis approach. RESULTS: Similar to prior
      work with 11C-thymidine, identifiability analysis showed that K1 (transport) and
      K(FLT) (flux) could be estimated independently for sufficiently high K1 values.
      However, estimation of K(FLT) was less robust at low K1 values, particularly
      those close to normal brain. K1 was higher for MRI contrast-enhancing (CE) tumors
      (0.053 +/- 0.029 mL/g/min) than noncontrast-enhancing (NCE) tumors (0.005 +/-
      0.002 mL/g/min; P < 0.02), and K(FLT) was higher for high-grade tumors (0.018 +/-
      0.008 mL/g/min, n = 9) than low-grade tumors (0.003 +/- 0.003 mL/g/min, n = 3; P
      < 0.01). The flux in NCE tumors was indistinguishable from contralateral normal
      brain (0.002 +/- 0.001 mL/g/min). For CE tumors, K1 was higher than K(FLT).
      Parametric images matched region-of-interest estimates of transport and flux.
      However, no patient has 18F-FLT uptake outside of the volume of increased
      permeability defined by MRI T1+Gd enhancement. CONCLUSION: Modeling analysis of
      18F-FLT PET data yielded robust estimates of K1 and K(FLT) for enhancing tumors
      with sufficiently high K1 and provides a clearer understanding of the
      relationship between transport and retention of 18F-FLT in gliomas. In tumors
      that show breakdown of the BBB, transport dominates 18F-FLT uptake. Transport
      across the BBB and modest rates of 18F-FLT phosphorylation appear to limit the
      assessment of cellular proliferation using 18F-FLT to highly proliferative tumors
      with significant BBB breakdown.

PMID- 17015897
TI  - 18F-FDG PET versus CT for the detection of enteropathy-associated T-cell lymphoma
      in refractory celiac disease.
AB  - Refractory celiac disease (RCD) can evolve into enteropathy-associated T-cell
      lymphoma (EATL). 18F-FDG PET has been reported to discriminate between RCD and
      EATL. Because prospective data are lacking, we designed a prospective study to
      evaluate the potential of 18F-FDG PET for detection of EATL in patients with RCD
      and compared the results with those obtained using abdominal CT in a referral
      center. METHODS: Between April 2003 and April 2005, 8 consecutive patients
      (median age, 66 y; range, 52-89 y) with EATL and 30 patients (median age, 61 y;
      range, 44-71 y) with RCD were included. CT and 18F-FDG PET were performed on all
      patients. Histologic evidence of EATL was identified in tissue samples obtained
      during upper gastrointestinal endoscopy or surgical resection. RESULTS: Villous
      atrophy was found in all patients with RCD and all (except 1) patients with EATL
      in nontumoral mucosa. Histologic examination of 1 patient with EATL localized in
      the duodenum showed intraepithelial lymphocytosis only. 18F-FDG PET could reveal
      sites histologically proven to be EATL in all 8 patients, whereas CT showed
      normal findings in 1 patient with EATL. 18F-FDG PET detected unsuspected
      extraintestinal sites affected by EATL in 2 patients. CT showed abnormalities
      such as a thickened small-bowel wall or lymphadenopathy in 14 patients with RCD
      lacking evidence of EATL at follow-up. 18F-FDG PET findings were positive in 3
      and equivocal in another 3 patients with RCD. 18F-FDG PET was more sensitive and
      specific than CT (100% vs. 87% and 90% vs. 53%, respectively). CONCLUSION: Our
      data show that 18F-FDG PET is more sensitive in detecting EATL in patients with
      RCD than is CT. 18F-FDG PET, in addition to conventional CT, is recommended for
      evaluating patients with RCD.

PMID- 17015898
TI  - 18F-FDG PET/CT of thymic epithelial tumors: usefulness for distinguishing and
      staging tumor subgroups.
AB  - The purpose of our study was to assess the usefulness of integrated PET/CT using
      18F-FDG for distinguishing thymic epithelial tumors according to the World Health
      Organization (WHO) classification. METHODS: Thirty-three patients (age range, 34
      68 y; mean age, 54.6 y) with thymic epithelial tumors, who underwent both
      integrated PET/CT and enhanced CT, were included. The clinicopathologic stages,
      maximum standardized uptake values (SUVs), and uptake patterns of tumors on
      integrated PET/CT images, and various enhanced CT findings, are described
      according to the simplified (low-risk [types A, AB, and B1] and high-risk [types
      B2 and B3] thymomas and thymic carcinomas) subgroups of the WHO classification.
      Discriminant analysis was performed to determine the relative capabilities of
      integrated PET/CT and enhanced CT findings to differentiate tumor subgroups.
      RESULTS: Tumors included 8 low-risk thymomas, 9 high-risk thymomas, and 16 thymic
      carcinomas. The maximum SUVs of high-risk thymomas (P < 0.001) and low-risk
      thymomas (P < 0.001) were found to be significantly lower than those of thymic
      carcinomas. Homogeneous 18F-FDG uptake within tumors was more frequently seen in
      thymic carcinomas than in high-risk thymomas (P = 0.027) or low-risk thymomas (P
      = 0.001). The uptake pattern (homogeneous vs. heterogeneous) on integrated PET/CT
      images and the presence of mediastinal fat invasion on enhanced CT images were
      found to be useful for differentiating tumor subgroups. In addition, integrated
      PET/CT helped detect lymph node metastases, which were not identified on enhanced
      CT in 2 patients. CONCLUSION: Integrated PET/CT was found to be useful for
      differentiating subgroups of thymic epithelial tumors and for staging the extent
      of the disease.

PMID- 17015899
TI  - Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic
      nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT.
AB  - The 11C-labeled tracer meta-hydroxyephedrine (11C-HED) is a noradrenaline analog
      that was developed to visualize the sympathetic nervous system with PET. Initial
      clinical studies show a rapid uptake of 11C-HED in localized tumors of this
      system. Whole-body imaging with 11C-HED PET is now possible as PET/CT scanners
      allow a rather short examination time. The aim of this study was to evaluate the
      feasibility of whole-body 11C-HED PET/CT for examination of tumors of the
      sympathetic nervous system and to directly compare the results with 123I-labeled
      meta-iodobenzylguanidine (123I-MIBG) scintigraphy, including SPECT/CT. METHODS:
      In 19 consecutive patients, 9 mo to 68 y old (median, 32 y), 24 whole-body 11C
      HED PET/CT (low-dose CT) examinations were performed. Scans were compared with
      attenuation-corrected 123I-MIBG SPECT/CT scans (24-h scan, low-dose CT). The
      intensity of tracer accumulation above background was visually analyzed in both
      scans, PET and SPECT, using a 4-value scale. In 11C-HED PET, mean and maximum
      standardized uptake values were determined for all lesions. RESULTS: In 14
      patients with 19 pairs of examinations, the following tumors were confirmed
      histologically: 6 neuroblastomas, 5 pheochromocytomas, 1 ganglioneuroblastoma,
      and 2 paragangliomas. In 5 patients, each having 1 pair of examinations, clinical
      follow-up and/or histologic examination did not reveal any tumor deriving from
      the sympathetic nervous system. 11C-HED PET/CT detected 80 of 81 totally depicted
      tumor lesions (sensitivity, 0.99; soft tissue, 61; bone, 19). 123I-MIBG SPECT/CT
      detected 75 of 81 lesions (sensitivity, 0.93; soft tissue, 56; bone, 19). With
      both methods, there were no false-positive lesions. The tumor-to-background
      contrast of 11C-HED uptake was higher in comparison with 123I-MIBG uptake in 26
      lesions (0.32; soft tissue, 18; bone, 8), equal in 39 lesions (0.48; soft tissue,
      30; bone, 9), and lower than 123I-MIBG uptake in 16 lesions (0.20; soft tissue,
      14; bone, 2). CONCLUSION: Whole-body imaging using 11C-HED PET/CT is feasible in
      the clinical setting of patients with tumors of the sympathetic nervous system.
      11C-HED PET/CT detected more tumor lesions than 123I-MIBG SPECT/CT. However,
      tumor-to-background contrast of 11C-HED in lesions can be higher, equal, or lower
      compared with 123I-MIBG.

PMID- 17015900
TI  - PET/CT in lymphoma: prospective study of enhanced full-dose PET/CT versus
      unenhanced low-dose PET/CT.
AB  - PET/CT combines functional and morphologic data and increases diagnostic accuracy
      in a variety of malignancies. This study prospectively compares the agreement
      between contrast-enhanced full-dose PET/CT and unenhanced low-dose PET/CT in
      lesion detection and initial staging of Hodgkin's disease and non-Hodgkin's
      lymphoma. METHODS: Forty-seven biopsy-proven lymphoma patients underwent a 18F
      FDG PET/CT study that included unenhanced low-dose CT and enhanced full-dose CT
      for initial staging. Patients who had undergone previous diagnostic CT for
      initial staging were excluded. For every patient, each modality of PET/CT images
      was evaluated by either of 2 pairs of readers, with each pair comprising 1
      experienced radiologist and 1 experienced nuclear physician. While evaluating one
      of the 2 types of PET/CT, the readers were unaware of the results of the other
      type. Lesion detection, number of sites affected in each anatomic region, and
      disease stage were assessed. Agreement between techniques was determined by the
      kappa-statistic, and discordances were studied by the McNemar test. Clinical,
      analytic, histopathologic, diagnostic CT, and PET data; data from other imaging
      techniques; and follow-up data constituted the reference standard. RESULTS: For
      region-based analysis, no significant differences were found between unenhanced
      low-dose PET/CT and contrast-enhanced full-dose PET/CT, although full-dose PET/CT
      showed fewer indeterminate findings and a higher number of extranodal sites
      affected than did low-dose PET/CT. Agreement between the 2 types of PET/CT was
      almost perfect for disease stage (kappa = 0.92; P < 0.001). CONCLUSION: Our study
      showed a good correlation between unenhanced low-dose PET/CT and contrast
      enhanced full-dose PET/CT for lymph node and extranodal disease in lymphomas,
      suggesting that unenhanced low-dose PET/CT might suffice in most patients as the
      only imaging technique for the initial staging of lymphomas, reserving diagnostic
      CT for selected cases.

PMID- 17015902
TI  - Understanding radiologic and nuclear terrorism as public health threats:
      preparedness and response perspectives.
AB  - Terrorism dates back to antiquity, but our understanding of it as a public health
      threat is still in its nascent stages. Focusing on radiation and nuclear
      terrorism, we apply a public health perspective to explore relevant physical
      health and psychosocial impacts, the evolving national response infrastructure
      created to address terrorism, and the potential roles of nuclear medicine
      professionals in preparing for and responding to radiologic and nuclear
      terrorism.

PMID- 17015901
TI  - PET of human prostate cancer xenografts in mice with increased uptake of 64CuCl2.
AB  - Our objective was to determine whether human prostate cancer xenografts in mice
      can be localized by PET using 64CuCl2 as a probe (64Cu PET). METHODS: Athymic
      mice bearing human prostate cancer xenografts were subjected to 64Cu PET,
      followed by quantitative analysis of the tracer concentrations and
      immunohistochemistry study of human copper transporter 1 expression in the tumor
      tissues. RESULTS: Human prostate cancer xenografts expressing high levels of
      human copper transporter 1 were well visualized on the PET images obtained 24 h
      after injection but not on the images obtained 1 h after injection. PET
      quantitative analysis demonstrated a high concentration of 64CuCl2 in the tumors
      in comparison to that in the left shoulder regions (percentage injected dose per
      gram of tissue: 3.6 +/- 1.3 and 0.6 +/- 0.3, respectively; P = 0.004), at 24 h
      after injection. CONCLUSION: The data from this study suggested that locally
      recurrent prostate cancer might be localized with 64Cu PET using 64CuCl2 as a
      probe.

PMID- 17015903
TI  - Evaluation of 3D Monte Carlo-based scatter correction for 99mTc cardiac perfusion
      SPECT.
AB  - Cardiac SPECT images are degraded by photons scattered in the thorax. Accurate
      correction for scatter is complicated by the nonuniform density and varied sizes
      of thoraxes and by the additional attenuation and scatter caused by female
      patients' breasts. Monte Carlo simulation is a general and accurate method for
      detailed modeling of scatter. Hence, for 99mTc we compared statistical
      reconstruction based on Monte Carlo modeling of scatter with statistical
      reconstruction that incorporates the more commonly used triple-energy-window
      scatter correction. Both of these scatter correction methods were used in
      conjunction with attenuation correction and resolution recovery. METHODS:
      Simultaneous attenuation, detector response, and Monte Carlo-based scatter
      correction were implemented via the dual-matrix ordered-subset expectation
      maximization algorithm with a Monte Carlo simulator as part of the forward
      projector (ADS-MC). ADS-MC was compared to (i) ordered-subset expectation
      maximization with attenuation correction and with detector response modeling
      (AD); (ii) like (i) but with scatter correction added using the triple-energy
      window method (ADS-TEW). A dual-detector SPECT system equipped with 2 153Gd
      scanning line sources was used for acquiring 99mTc emission data and attenuation
      maps. Four clinically realistic phantom configurations (a large thorax and a
      small thorax, each with and without breasts) with a cardiac insert containing 2
      cold defects were used to evaluate the proposed reconstruction algorithms. In
      these phantom configurations, we compared the performance of the algorithms in
      terms of noise properties, contrast-to-noise ratios, contrast separability of
      cold defects, and robustness to anatomic variation. RESULTS: Noise was found to
      be approximately 14% lower in the ADS-MC images than in the ADS-TEW and AD
      images. Typically, the contrast obtained with the ADS-MC algorithm was 10%-20%
      higher than that obtained with the other 2 methods. Furthermore, compared with
      the other 2 algorithms, the ADS-MC method was less sensitive to anatomic
      variations. CONCLUSION: Our results indicate that the imaging performance of
      99mTc SPECT can be improved more by Monte Carlo-based scatter correction than by
      window-based scatter correction.

PMID- 17015904
TI  - Molecular therapy of human neuroblastoma cells using Auger electrons of 111In
      labeled N-myc antisense oligonucleotides.
AB  - Auger electrons can create breaks in nucleic acids, giving them possible
      therapeutic utility. We investigated the therapeutic effect of Auger electrons
      emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human
      neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ
      neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase
      evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol
      of oligonucleotides/mumol of total phospholipids) that had an average diameter of
      250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger
      RNA (mRNA), N-myc expression, and cell proliferation were investigated. The
      tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled
      antisense, 111In-labeled sense, or empty cationic REVs were used as controls.
      RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected
      in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc
      expression and inhibited cell proliferation were shown in the same cells at 48 h
      after the completion of treatment. N-myc expression-suppressed cells produced
      intraperitoneal tumors in nude mice, but the average weight of the tumors was
      lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted
      from 111In in close proximity to their target N-myc mRNA may prolong the time to
      cell proliferation in human neuroblastoma cells due to inhibition of the
      translation of N-myc. Auger electron therapy therefore has potential as an
      internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

PMID- 17015905
TI  - Bispecific antibody pretargeting PET (immunoPET) with an 124I-labeled hapten
      peptide.
AB  - We previously described a highly flexible bispecific antibody (bs-mAb)
      pretargeting procedure using a multivalent, recombinant anti-CEA
      (carcinoembryonic antigen) x anti-HSG (histamine-succinyl-glycine) fusion protein
      with peptides radiolabeled with 111In, 90Y, 177Lu, and 99mTc. The objective of
      this study was to develop a radioiodination procedure primarily to assess PET
      imaging with 124I. METHODS: A new peptide, DOTA-D-Tyr-D-Lys(HSG)-D-Glu-D-Lys(HSG)
      NH2 (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), was
      synthesized and conditions were established for radioiodination with yields of
      approximately 70% for 131I and 60% for 124I. Pretargeting with the 131I- and 124I
      labeled peptide was tested in nude mice bearing LS174T human colonic tumors that
      were first given the anti-CEA x anti-HSG bs-mAb. Imaging (including small-animal
      PET) and necropsy data were collected at several intervals over 24 h. Comparisons
      were made between animals given 124I-anti-CEA Fab', 18F-FDG, the same peptide
      radiolabeled with 111In and pretargeted with the bs-mAb, and the radioiodinated
      peptide alone. RESULTS: The radioiodinated peptide alone cleared quickly from the
      blood with no evidence of tumor targeting, but when pretargeted with the bs-mAb,
      tumor uptake increased 70-fold, with efficient and rapid clearance from normal
      tissues, allowing clear visualization of tumor within 1-2 h. Tumor uptake
      measured at necropsy was 3- to 15-fold higher and tumor-to-blood ratios were 10-
      to 20-fold higher than those for 124I-Fab' at 1 and 24 h, respectively. Thyroid
      and stomach uptake was observed with the radioiodinated peptide several hours
      after injection (animals were not premedicated to reduce uptake in these
      tissues), but gastric uptake was much more pronounced with 124I-Fab'. Tumor
      visualization with 18F-FDG at approximately 1.5 h was also good but showed
      substantially more uptake in several normal tissues, making image interpretation
      in the pretargeted animals less ambiguous than with 18F-FDG. CONCLUSION:
      Bispecific antibody pretargeting has a significant advantage for tumor imaging
      over directly radiolabeled antibodies and could provide additional enhancements
      for oncologic imaging, particularly for improving targeting specificity as
      compared with 18F-FDG.

PMID- 17015906
TI  - 11C-JHU75528: a radiotracer for PET imaging of CB1 cannabinoid receptors.
AB  - The development of the radioligands for PET imaging of the cerebral cannabinoid
      receptor (CB1) is of great importance for studying its role in neuropsychiatric
      disorders, obesity, and drug dependence. None of the currently available
      radioligands for CB1 are suitable for quantitative PET, primarily because of
      their insufficient binding potential (BP) in brain or low penetration through the
      blood-brain barrier (BBB). The goal of this study was to evaluate 11C-JHU75528,
      an analog of the selective CB1 antagonist rimonabant, in vivo as a potential CB1
      radioligand for PET. METHODS: The brain regional distribution and pharmacology of
      11C-JHU75528 have been evaluated in vivo in mice (dissection) and baboons (PET).
      RESULTS: 11C-JHU75528 readily entered the mouse and baboon brain and specifically
      and selectively labeled cerebral CB1 receptors. The ratio of striatum to brain
      stem in mice and the binding potential (BP) in the baboon putamen were 3.4 and
      1.3-1.5, respectively. The specific binding of 11C-JHU75528 in vivo was blocked
      by preinjection of nonlabeled JHU75528. Administration of rimonabant (1 mg/kg,
      intravenously) also blocked the specific binding of 11C-JHU75528 in the mouse and
      baboon brain, whereas various central noncannabinoid drugs did not significantly
      reduce the 11C-JHU75528 binding in the mouse brain. 11C-JHU75528 formed several
      hydrophilic metabolites, but only a minute fraction of metabolic radioactivity
      penetrated the BBB. CONCLUSION: 11C-JHU75528 holds promise as a radiotracer with
      suitable imaging properties for quantification of CB1 receptors in the human
      brain.

PMID- 17015907
TI  - Synthesis and biologic evaluation of a novel serotonin 5-HT1A receptor
      radioligand, 18F-labeled mefway, in rodents and imaging by PET in a nonhuman
      primate.
AB  - Serotonin 5-HT1A receptors have been implicated in disorders of the central
      nervous system and, therefore, are being studied by PET. Efforts are under way to
      improve in vivo stability of 5-HT1A agents currently in human use (11C-labeled N
      (2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohexanecarboxamide
      [11C-WAY-100635], 4-(2'-methoxyphenyl)-1-[2'-(N-2''-pyridinyl)-p-18F
      fluorobenzamido]ethylpiperazine [18F-MPPF], and 18F-labeled trans-4-fluoro-N-(2
      [4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide
      [18F-FCWAY]). We have synthesized N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N
      (2-pyridyl)-N-(4-18F-fluoromethylcyclohexane)carboxamide (18F-mefway), which
      contains a 18F on a primary carbon to make the compound more stable to
      defluorination. METHODS: Radiosynthesis of 18F-mefway was performed in a single
      tosylate for 18F-fluoride exchange. In vitro binding studies on rat brain slices
      using 18F-mefway were read on a phosphor imager. Monkey PET studies were
      performed on a whole-body PET scanner. RESULTS: Binding affinity (inhibitory
      concentration of 50% [IC50]) of mefway was 26 nmol/L and was comparable to that
      of WAY-100635, 23 nmol/L. Yields of 18F-mefway were 20%-30% in specific
      activities of 74-111 GBq/micromol at the end of synthesis. In vitro binding of
      18F-mefway in the hippocampus (Hp), colliculus (Co), cortex (Ctx), and other
      brain regions-with limited binding in the cerebellum (Cer)--was observed, with
      ratios of Hp/Cer = 82.3, Co/Cer = 45.8, and Ctx/Cer = 40. Serotonin displaced 18F
      mefway from various brain regions with IC50 values in the range of 169-243
      nmol/L. PET studies in a rhesus monkey showed 18F-mefway binding in the fontal
      cortex (FC), temporal cortex (TC) including hippocampus, raphe (Rp), and other
      brain regions, with ratios of FC/Cer = 9.0, TC/Cer = 10, and Rp/Cer = 3.3. Plasma
      analysis indicated the presence of approximately 30% of 18F-mefway at 150-180 min
      after injection. CONCLUSION: The high ratios in specific brain regions such as
      the hippocampus suggest that 18F-mefway has potential as a PET agent for 5HT1A
      receptors.

PMID- 17015908
TI  - Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B
      fibronectin antibody fragments.
AB  - The aim of this study was to target the angiogenesis-associated extracellular
      matrix protein ED-B fibronectin for molecular imaging of solid tumors.
      Recombinant and chemically modified derivatives of the single-chain antibody
      fragment (scFv) L19, capable of being labeled with 99mTc, were synthesized and
      radiolabeled. The resulting compounds 99mTc-AP39, 99mTc-L19-His, and 99mTc-L19
      Hi20 were assessed for their imaging properties in vivo. METHODS: L19 was
      genetically modified by inserting either the (Gly)3-Cys-Ala (AP39) or a (His)6
      tag (L19-His) sequence at the C-terminal end. Chemical modifications were
      performed by conjugating the bifunctional chelator Hi20 (L19-Hi20) at epsilon-Lys
      NH2 residues of the molecule to allow for a direct chelator-based labeling with
      99mTc. Tumor-targeting, pharmacokinetic, and scintigraphic imaging properties of
      the radiolabeled scFvs were evaluated in nude mice bearing murine F9
      teratocarcinoma. RESULTS: 99mTc labeling of the L19 derivatives yielded
      radiochemically pure proteins maintaining high immunoreactivity to ED-B
      fibronectin, as measured by affinity chromatography. Size-exclusion high
      performance liquid chromatographic analysis of labeled L19 derivatives
      demonstrated either dimeric species (L19-His) or a mixture of predominantly
      associative dimeric and monomeric species (AP39, L19-Hi20). 99mTc-AP39 showed the
      most favorable biodistribution and imaging properties with high and fast tumor
      uptake (8.3 percentage injected dose per gram at 3 h after injection), rapid
      blood clearance and renal excretion, leading to high signal-to-noise ratios
      (tumor-to-blood ratio of 6.4 at 3 h after injection), and excellent planar
      scintigraphy in vivo. CONCLUSION: ED-B fibronectin can be efficiently targeted by
      99mTc-AP39 and scintigraphically visualized in tumor-bearing mice, providing a
      potentially useful clinical tool for imaging of angiogenesis-associated ED-B
      fibronectin-expressing human tumors.

PMID- 17015909
TI  - Evaluation of 4'-[methyl-14C]thiothymidine for in vivo DNA synthesis imaging.
AB  - We evaluated 4'-[methyl-11C]thiothymidine ([methyl-11C]S-dThd) to obtain a
      thymidine analog that might prove simpler to use for imaging DNA synthesis and
      that might follow the same biochemistry as its surrogate. METHODS: [Methyl-14C]S
      dThd was synthesized by rapid methylation of 5-trimethylstannyl-4'-thio-2'
      deoxyuridine via a palladium-mediated Stille coupling reaction with 14C-methyl
      iodide. Degradation of [methyl-14C]S-dThd, when incubated in human blood, was
      analyzed by high-performance liquid chromatography (HPLC). The in vivo potential
      of [methyl-14C]S-dThd was evaluated by studying its distribution in EMT-6 mammary
      carcinoma-bearing mice. 2-Fluoro-2'-deoxycytidine, a potent inhibitor of DNA
      synthesis, was used to modulate cell proliferation. Tissue extraction was also
      performed to investigate the incorporation of [methyl-14C]S-dThd into DNA.
      RESULTS: [Methyl-14C]S-dThd was obtained in a 31%-41% radiochemical yield
      (calculated from 14C-methyl iodide) at 130 degrees C, 5-min reaction in N,N
      dimethylformamide followed by semipreparative HPLC purification. The
      radiochemical purity of [methyl-14C]S-dThd was >99% and the specific activity was
      2.04 GBq/mmol (according to the specific activity of 14C-methyl iodide). [2
      14C]Thymidine, when incubated with human blood, demonstrated rapid degradation.
      In contrast, [methyl-14C]S-dThd was stable with <3% degradation at 60 min. An in
      vivo distribution study showed the accumulation of radioactivity in proliferating
      tissues (spleen, thymus, duodenum, and tumor). On the other hand, the
      radioactivity of nonproliferating tissues (lung, liver, kidney, and muscle) was
      rapidly cleared in parallel with the clearance of blood radioactivity. The tumor
      uptake of [methyl-14C]S-dThd was high (8.8 percentage injected dose per gram at
      60 min) and selective (tumor-to-blood ratio, 12.2 at 60 min). 2-Fluoro-2'
      deoxycytidine pretreatment significantly reduced the tumor uptake of [methyl
      14C]S-dThd. Relative blood flow as measured by the uptake of 4-[N-methyl
      14C]iodoantipyrine was similar between the treated and untreated groups. Tissue
      extraction studies showed that most of the total tissue radioactivity of rapidly
      proliferating tissues was recovered in the DNA fraction at 60 min after [methyl
      14C]S-dThd injection. CONCLUSION: The labeling procedure is rapid and suitable
      for 11C labeling. Positron-labeled 4'-thiothymidine should be useful for imaging
      DNA synthesis by PET.

PMID- 17015910
TI  - 131I ablation treatment in young females after the Chernobyl accident.
AB  - The Chernobyl accident resulted in a number of cases of thyroid cancer in females
      under the age of 20 y. Many of these individuals were treated with surgical
      removal of the thyroid gland followed by 131I ablation of residual thyroid
      tissue. Epidemiologic evidence demonstrates that 131I treatment for thyroid
      cancer or hyperthyroidism in adult women confers negligible risk of breast
      cancer. However, comparable data for younger women do not exist. Studies of
      external radiation exposure indicate that, for radiation exposures of as low as
      0.2-0.7 Gy, the risk of breast cancer is greater for infant and adolescent female
      breast tissues than for adult female breast tissues. METHODS: The effective half
      time of 131I measured in athyrotic patients was used together with the OLINDA/EXM
      computer code to estimate doses to breast tissue in 10-y-old, 15-y-old, and young
      adult females from ablation treatment. RESULTS: The dose to pediatric and young
      adult female breast tissue associated with a 5.6-GBq (150 mCi) ablation treatment
      may range from 0.35 to 0.55 Gy, resulting in a lifetime risk of breast cancer
      ranging from 2-4 cases per 100 such individuals exposed and a lifetime risk of
      solid tumors ranging from 8 to 17 solid tumors per 100 such individuals exposed.
      Administration of multiple ablation treatments, as often occurs with metastases,
      could result in doses ranging from 0.7 to 1 Gy, with corresponding increases in
      the lifetime cancer risk. CONCLUSION: These estimates suggest the need for
      additional research and a possible need for surveillance of young Chernobyl
      thyroid cancer patients who received 131I ablation treatment.

PMID- 17015911
TI  - Inhibition of kidney uptake of radiolabeled somatostatin analogs: amino acids or
      gelofusine?

PMID- 17015913
TI  - Safety of 18F-DOPA injection for PET of carcinoid tumor.

PMID- 17015915
TI  - CT attenuation correction is clinically superior to supine-prone MPS.

PMID- 17015916
TI  - Catheter-induced coronary artery dissection: risk factors, prevention and
      management.
AB  - Guide catheter-induced dissection of the coronary arteries is an uncommon but
      potentially catastrophic complication of diagnostic and interventional cardiac
      catheterization. Several factors placing the individual at higher risk of this
      complication have been identified. We discuss these risk factors and utilize them
      to propose methods to prevent dissections. Management options of coronary artery
      dissection are also discussed.

PMID- 17015917
TI  - Mitral annuloplasty causing left circumflex injury and infarction: novel use of
      intravascular ultrasound to diagnose suture injury.
AB  - Suture injury of the left circumflex coronary artery and infarction may be an
      under-recognized complication of mitral valve annuloplasty. Our cases illustrate
      a potential role for early coronary angiography in patients who have persistent
      hemodynamic instability or ventricular irritability, which may be related to left
      circumflex artery injury. This potentially devastating complication of mitral
      annuloplasty can be diagnosed by use of intravascular ultrasound to distinguish
      suture injury from an atherosclerotic lesion.

PMID- 17015918
TI  - A patient with hypertrophic obstructive cardiomyopathy presenting with left
      ventricular apical ballooning syndrome.

PMID- 17015919
TI  - Transradial bilateral iliac stenting.
AB  - Bilateral stenting of the common iliac arteries via the radial access route, in
      the same setting, is presented in this case report. Radial access limits bleeding
      complications, avoids the crossover technique and allows same-day discharge.

PMID- 17015920
TI  - Crossing a chronic total occlusion using combination therapy with Tornus and
      FlowCardia.

PMID- 17015921
TI  - Accelerated atherosclerosis: how fast can it develop?

PMID- 17015922
TI  - Transcatheter closure of acquired Gerbode defect following mitral valve
      replacement using the Amplatzer duct occluder.

PMID- 17015923
TI  - Use of the PercuSurge GuardWire distal balloon occlusion system as an
      endovascular clamp during off-pump coronary bypass surgery with the LIMA to the
      LAD.
AB  - Off-pump coronary bypass surgery is an alternative to conventional bypass surgery
      and has the potential to reduce perioperative morbidity. Current techniques of
      snaring or inserting a shunt into the coronary artery to occlude flow and allow
      for anastomotic construction carry the risk of vessel trauma and subsequent graft
      failure. We present two cases in which PercuSurge GuardWires were used as an
      endovascular clamp in a hybrid operating room/catheterization laboratory to
      transiently occlude flow down the native left anterior descending artery during
      left internal mammary artery anastamotic construction.

PMID- 17015924
TI  - Rising rates of caesarean section: the way ahead.

PMID- 17015925
TI  - Computer-aided diagnosis: radiologists' "second opinion" in breast cancer
      diagnosis on mammography.

PMID- 17015926
TI  - Neuroleptospirosis: unexplored & overlooked.

PMID- 17015927
TI  - The requirements of protein & amino acid during acute & chronic infections.
AB  - Nutrition and infection interact with each other in a synergistic vicious cycle,
      leading to an adverse nutritional status and increased susceptibility to
      infection. Infectious episodes result in hypermetabolism and a negative nitrogen
      balance which is modulated by hormones, cytokines and other pro-inflammatory
      mediators, and is compounded by a reduced food intake. The extent of the negative
      nitrogen balance varies with the type of infection and its duration; however, it
      is reasonable to suggest that the loss of body protein could be minimized by the
      provision of dietary nitrogen, although anorexia will limit this. Further,
      distinctions need to be made about the provision of nutrients or protein during
      the catabolic and anabolic or recovery phase of the infection, since the capacity
      of the body to retain protein is enhanced in the anabolic recovery phase. Meeting
      the increased requirement for protein (and other nutrients) in infection does not
      imply a complete therapeutic strategy. Infections need to be treated
      appropriately, with nutrition as an adjunct to the treatment. Prior
      undernutrition could also impair the body's response to infection, although the
      weight of the evidence would suggest that this happens more particularly in
      oedematous undernutrition. In general, the amount of extra protein that would
      appear to be needed is of the order of 20-25 per cent of the recommended intake,
      for most infections. In acute infections, this is particularly relevant during
      the convalescence period. Community trials have suggested that lysine
      supplementation to the level required for normal daily nutriture, in
      predominantly wheat eating or potentially lysine deficient communities, improves
      immune function among other functional nutritional parameters; however, there is
      as yet insufficient evidence to suggest a specific requirement for amino acids in
      infections over and above the normal daily requirement as based on recent
      evidence. Some clinical studies that have showed benefits with specific amino
      acids through selected clinical outcomes, however, these do not provide enough
      evidence for a firm recommendation.

PMID- 17015928
TI  - Computer aided decision system for early detection of breast cancer.
AB  - BACKGROUND & OBJECTIVES: Mammography is currently the method of choice for early
      detection of breast cancer in women. However, the interpretation of mammograms is
      largely based on radiologist's opinion. In this study an attempt is made to
      develop an image processing algorithm for the detection of microcalcifications
      and also a computer based decision system for early detection of breast cancer.
      The proposed method deals with a novel approach for the development of a computer
      aided decision (CAD) system for early detection of breast cancer by mammogram
      image analysis. METHODS: The proposed method employs simple thresholding the
      region of interest and the use of filters for clear identification of
      microcalcifications. The method suggested for the detection of
      microcalcifications from a mammogram image segmentation and analysis was tested
      over several images taken from mini-MIAS (Mammogram Image Analysis Society, UK)
      database. The algorithm was implemented using Metlab codes programming and hence
      can work effectively on a simple personal computer with digital mammogram as
      stored data for analysis. RESULTS: The algorithm works faster so that any
      radiologist can take a clear decision about the appearance of microcalcifications
      by visual inspection of digital mammograms. The performance of the algorithm was
      tested over several images and the validation of results by visual inspection
      were done by an expert radiologist. Also, the system has given good detection
      rate as high as 78 percent. The performance analysis of the CAD algorithm was
      done by receiver operating characteristics (ROC) plot. INTERPRETATION &
      CONCLUSION: The CAD system suggested here was capable of detecting
      microcalcifications with a high detection rate, and thus could be used for early
      detection of breast cancer.

PMID- 17015929
TI  - Neuroleptospirosis - revisited: experience from a tertiary care neurological
      centre from south India.
AB  - BACKGROUND & OBJECTIVES: Leptospirosis is a zoonotic disease commonly reported
      from south India. Neurological manifestations seen in about 10-15 per cent of
      cases, are protean and remain unrecognized and diverse. We evaluated the pattern
      of nervous system involvement in leptospirosis, among patients presenting to the
      emergency services of a tertiary care neurological centre in south India, and
      also analysed the outcome and prognostic indicators. METHODS: The diagnosis of
      neuroleptospirosis was based on clinical and laboratory evidence of hepatorenal
      syndrome, and serum or CSF positivity for antileptospira antibody by a
      macroscopic agglutination test (MAT) and by ELISA in a limited number of samples.
      RESULTS: A total of 31 patients (M:F 27:4, age range 6-68 yr, mean 36.4 +/- 14.3
      yr) were treated during the five year period. Acute fever with chills and rigors,
      headache and vomiting were the presenting manifestations; 25 patients (81%) had
      altered sensorium for a period ranging from 1- 8 days, four (12.9%) being deeply
      comatose. Eleven (35.5%) had acute symptomatic seizures at the time of
      presentation. Conjunctival congestion with or without haemorrhage was seen in 12
      patients (38.7%), icterus in 14 (45%) and mild hepatosplenomegaly in 11 (35.5%).
      Early papilloedema was observed in three. Only three patients had localizing
      deficits. CT scan was normal in 18 of 27 (67%), while 7 (26%) had diffuse
      cerebral oedema. CSF pleocytosis with lymphocytic predominance (mean 50
      cells/microl) and elevated protein levels (mean 115.5 +/- 67.5 mg %) were noted.
      Leptospira antibody was detected in serum of all, and 5 of 22 in CSF samples.
      Eight patients (26%) succumbed. Deep altered sensorium at presentation and raised
      CSF protein were two poor prognostic indicators. Pathological study of brain in
      five cases revealed encephalitic features and in addition immune mediated acute
      disseminated encephalomyelitis (ADEM) like pathology in two cases. INTERPRETATION
      & CONCLUSION: Neuroleptospirosis should be considered in the differential
      diagnosis of neuroinfections associated with hepatorenal dysfunction, in endemic
      areas. Leptospira antibody can be detected in CSF also in some cases. Deep
      altered sensorium at presentation indicates poor prognosis.

PMID- 17015930
TI  - A random sample survey for prevalence of major neurological disorders in Kolkata.
AB  - BACKGROUND & OBJECTIVES: Large scale epidemiological studies on neurological
      disorders are very few in India. We therefore planned to conduct a cross
      sectional population-based epidemiological study on a stratified randomly
      selected sample from the city of Kolkata to study the prevalence of major
      neurological disorders such as epilepsy, stroke, dementia and Parkinsonism.
      METHODS: The method of case ascertainment was two- stage house-to-house survey;
      the first stage was undertaken by a field team consisting of four field workers
      and a neuropsychologist. Screening questionnaire based on National Institute of
      Mental Health and Neuro Sciences (NIMHANS) protocol was used. In the second stage
      a neurologist examined all the screened positive cases. RESULTS: A total of
      52,377 subjects participated in the study. The crude prevalence rates (per
      100,000 population) of major neurological disorders with 95 per cent confidence
      intervals (95% CI) and age adjusted rates (AAR) based on US 2000 population were
      557.5 (95% CI 496.17-624.40 and AAR - 516.77) in epilepsy, 486.85 (95% CI 377.0
      to 551.11 and AAR-765.68) in stroke, 87.82 (95% CI 64.02-117.50 and AAR-168.4) in
      dementia and 45.82 (95% CI 29.64-67.63 and AAR-71.64) in Parkinsonism. The
      weighted prevalence rates (per 100,000) of the whole population based on re
      screening of 10 per cent of negative samples were 763.89 (95% CI 690.55- 842.57)
      in epilepsy, 624.32 (95% CI 555.64-699.24) in stroke and 139.37 (95% CI 108.71
      176.06) in dementia. INTERPRETATION & CONCLUSION: A high rate of stroke and
      overall lower prevalence of Parkinsonism and dementia was recorded as compared to
      western studies. High prevalence rate of stroke emphasizes the need to study
      incidence, morbidity and mortality profile of stroke including its socio-economic
      impact and also case-control analysis to determine the underlying risk factors.

PMID- 17015931
TI  - Prevalence of anaemia in pregnant & lactating women in India.
AB  - BACKGROUND & OBJECTIVES: The prevalence of anaemia during pregnancy and lactation
      was significantly lower in the National Family Health Survey 1998-1999 (NFHS-2),
      using the hemocue method for haemoglobin estimation compared to earlier surveys.
      The present study selected seven States and used the same districts and villages
      studied in the NFHS-2, to see if the reported reduction in prevalence of anaemia
      was due to health and nutrition inputs and/or due to a different method for
      haemoglobin estimation. METHODS: A total of 1,751 women (1,148 pregnant and 603
      lactating- exclusively breastfeeding up to 3 months of age), from seven States-
      Himachal Pradesh and Haryana in north; Assam and Orissa in east; Kerala and Tamil
      Nadu in south and Madhya Pradesh in central India, were selected. Haemoglobin was
      estimated by the cyanmethaemoglobin method, so that comparison was possible with
      earlier studies. Data on socio-demographic characteristics, pregnancy,
      nutritional status and dietary intakes were collected. RESULTS: Prevalence as
      well as severity of anaemia was significantly higher in the present study as
      compared to the NFHS-2 study data. The difference could be due to haemocue
      method, which gives higher haemoglobin values. The contributing factors found on
      multiple regression analysis for anaemia in pregnancy and lactation were:
      literacy, occupation and standard living index of the study women; their
      awareness about anaemia, its prevention by regular consumption of ironfolate
      tablets and increase in food intake. Maternal height, age of marriage, parity and
      foetal loss also contributed to haemoglobin level. There were interstate
      differences; lower fertility, higher literacy and better diet was observed in
      Himachal Pradesh as compared to Haryana. The literacy and nutritional status of
      women in Tamil Nadu was lower than Kerala. The remaining 3 states had poor
      fertility, lower social living index and nutritional status with >90 per cent
      women being anaemic in pregnancy and lactation. Low prevalence of severe anaemia
      in Orissa as compared to Assam was due to availability and consumption of iron
      folate tablets. The antenatal services in the first trimester and checkup by a
      doctor, along with availability and consumption of iron folate tablets over 3
      months in all the States influenced haemoglobin levels. INTERPRETATION &
      CONCLUSION: Despite the measures taken to control anaemia in pregnancy and
      lactation in the last two decades, the severity of nutritional anaemia continues
      to remain a public health issue of great magnitude, suggesting that these
      measures have been largely ineffective. The present findings also showed
      interstate differences particularly in fertility, women education, nutrition
      status and occupation; availability of antenatal services and iron folate tablets
      as possible factors responsible for differences in prevalence of anaemia.

PMID- 17015932
TI  - Prevalence of proteinuria in rural adult population in Tamil Nadu.
AB  - BACKGROUND & OBJECTIVES: Presence of proteinuria is considered as an early marker
      of an increased risk of progressive kidney disease. Angiotensin converting enzyme
      (ACE) inhibitors (ACEi) and angiotensin II receptor blockers (ARB) treatment to
      persons with proteinuria and chronic kidney disease has been shown to decrease
      the progression to endstage renal disease. As the exact prevalence of proteinuria
      is not known in the general population, we undertook this study to estimate the
      same in a rural adult population in Vellore district, Tamil Nadu. METHODS: A
      convenient sample of 5,043 adults was included. All individuals were tested for
      albuminuria by albumin dipstick examination in an untimed urine sample.
      Individuals who tested positive for albuminuria underwent a second dipstick
      examination after a gap of one week. Individuals with persistent albuminuria on
      the second dipstick examination underwent further evaluation which included
      medical history, physical examination, 24 h urine protein estimation, total serum
      protein and albumin estimation. Ultrasound of the abdomen was done in patients
      with renal failure and renal biopsy was performed in selected patients. RESULTS:
      Of the total 5,043 individuals screened, 63.1 per cent were females. Mean age of
      the study population was 50.94 +/- 11.2 yr. First dipstick test identified 594
      individuals positive for albuminuria. Repeat dipstick could be done in only 576,
      of whom 212 showed persistent albuminuria. Significant proteinuria was detected
      in 24 individuals of the 208 who had 24 h urine protein measured. Of these 24
      patients, 3 were found to have chronic renal failure, 12 were presumed to have
      diabetic nephropathy clinically, one each had focal segmental glomerulosclerosis
      and biopsy proven diabetic nephropathy, and 7 patients had proteinuria of unknown
      aetiology. INTERPRETATION & CONCLUSION: The prevalence of proteinuria in this
      adult rural population was 0.47 per cent (0.30-0.67%). The detection and
      treatment of chronic kidney disease in 24 individuals is bound to reduce the rate
      of decline of renal functions. Screening programme for proteinuria in different
      parts of country may be an effective measure to bring a decline in rate of
      progression of chronic kidney disease in general population.

PMID- 17015933
TI  - Multidrug resistance in amoebiasis patients.
AB  - BACKGROUND & OBJECTIVES: Amoebiasis, caused by Entamoeba sp. a protozoan
      parasite, is a major public health problem in tropical and subtropical countries.
      The symptomatic patients are treated by specific chemotherapy. However, there are
      reports of treatment failure in some cases suggesting the possibility of drug
      resistance. The present study was therefore planned to assess the presence and
      expression of mRNA of multidrug resistance (MDR) gene in clinical isolates of
      Entamoeba histolytica and E. dispar. METHODS: Forty five clinical isolates of
      Entamoeba sp. [E. histolytica (15) and E. dispar (30)] were maintained in
      polyxenic followed by monoxenic medium. DNA and total RNA were extracted from
      clinical isolates of Entamoeba sp. and from sensitive strain of E. histolytica
      (HM1: IMSS) and subjected to polymerase chain reaction (PCR) and multiplex
      reverse transcription (RT)-PCR techniques. RESULTS: The 344 bp segment of E.
      histolytica DNA was seen by PCR using primers specific to EhPgp1 in all clinical
      isolates and sensitive strain of E. histolytica. Over expression of EhPgp1 was
      observed only in resistant mutant of E. histolytica; however, transcription of
      EhPgp1 was not seen in any clinical isolates and sensitive strain of E.
      histolytica. INTERPRETATION & CONCLUSION: The findings of the present study
      indicate that, so far, drug resistance in clinical isolates of E. histolytica
      does not seem to be a major problem in this country. However, susceptibility of
      clinical isolates of E. histolytica against various antiamoebic drugs needs to be
      investigated for better management.

PMID- 17015934
TI  - Pharyngeal carriage of group A streptococci in school children in Chennai.
AB  - BACKGROUND & OBJECTIVES: Asymptomatic pharyngeal carriage of group A streptococci
      (GAS) in children may lead to spread of respiratory infections in the community.
      Data on healthy GAS carriers in the community are therefore important. We carried
      out this preliminary study to screen the school children from various parts of
      Chennai city, south India to detect pharyngeal carriage of GAS. METHODS: Throat
      swabs were collected from 1,173 school children aged 5 to 17 yr from different
      locations in Chennai. The isolates of beta haemolytic streptococci were
      serogrouped by agglutination tests using specific antisera. RESULTS: Beta
      haemolytic streptococci were isolated from 16.3 per cent of 1,102 asymptomatic
      children. 71 children of the study group had untreated tonsillitis positive for
      beta haemolytic streptococci. The percentage of asymptomatic GAS carriers was 8.4
      per cent. INTERPRETATION & CONCLUSION: The high carriage rate of beta haemolytic
      streptococci seen in children poses a threat to the community and should be
      checked. Regular screening needs to be done in various parts of the country.

PMID- 17015935
TI  - The effect of Panax ginseng on forced immobility time & immune function in mice.
AB  - BACKGROUND & OBJECTIVES: Panax ginseng has been used as a traditional medicine
      for many years mainly among Asian peoples for developing physical strength. We
      undertook this study to determine the immune-enhancement effect of P. ginseng
      using a forced swimming test (FST) and by measuring cytokine production in MOLT-4
      cell culture and mouse peritoneal macrophages. METHODS: P. ginseng was orally
      administered to mice once a day for 7 days. The anti-immobility effect of P.
      ginseng on the FST and blood biochemical parameters related to fatigue, glucose
      (Glc); blood urea nitrogen (BUN); latic dehydrogenase (LDH); total protein (TP)
      and production of cytokines in human T cell line, MOLT-4 cells and mouse
      peritoneal macrophages were investigated. RESULTS: After two and seven days, the
      immobility time was decreased in the P. ginsengadministrated mice as compared to
      the control group; however, this reduction was not significant. In addition, the
      amount of TP in the blood serum was significantly increased. However, the levels
      of Glc, BUN, and LDH did not show a significant change. P. ginseng significantly
      (P<0.05) increased interferon (IFN)-gamma production and expression as compared
      to control at 48 h in MOLT-4 cells. P. ginseng plus recombinant IFN-gamma instead
      of P. ginseng alone significantly increased the production of the tumour necrosis
      factor (TNF)-alpha in the mouse peritoneal macrophages. INTERPRETATION &
      CONCLUSION: Our results suggest that P. ginseng may be useful for an immune
      promoter. Further studies are needed to understand the mechanism of its action.

PMID- 17015936
TI  - Reduced antioxidant potential & sensitivity to oxidation in plasma low density
      lipoprotein fraction in type 2 diabetes mellitus patients.
AB  - BACKGROUND & OBJECTIVES: The aim of this study was to investigate LDL oxidation
      in the ethiopathogenesis of diabetes mellitus. Diabetes mellitus a disease caused
      due to severe insulin dysfunction, is associated with lipid and protein metabolic
      disorders. METHODS: A total of 90 type 2 diabetes patients were grouped according
      to their glycoted haemoglobin (HbA1c) values as regulated (<5.7%), poorly
      regulated (5.7 - 7.7%) and unregulated (>7.7%). Further, a healthy control group
      of 37 individuals was included for comparison in terms of sensitivity of low
      density lipoprotein (LDL) to oxidation and measurements of antioxidant potential
      (AOP). A heparin - citrate precipitation method was used to obtain LDL from the
      serum samples of patients and control groups. The LDL fractions were exposed to
      oxidation with CuSO4 and sensitivity to oxidation was evaluated. Ten patients
      each from regulated and unregulated groups, and 10 healthy controls were examined
      for antioxidant potential. RESULTS: The sensitivity of LDL fraction to oxidation
      was significantly lower in all diabetic groups compared to the control group. AOP
      was significantly decreased in unregulated diabetic group compared to the control
      group. INTERPRETATION & CONCLUSION: We hypothesize that oxidant stress increases
      in diabetes mellitus and oxidant defense systems weaken during the chronic course
      of the illness. Due to decreased antioxidant potential, that probably shortens
      the LDL oxidation lag phase, the sensitivity to oxidation appears to be lower in
      diabetes mellitus patients.

PMID- 17015937
TI  - Seroprevalence of Japanese encephalitis virus infection in Lucknow, Uttar
      Pradesh.

PMID- 17015938
TI  - Connexin 32 as an anti-invasive and anti-metastatic gene in renal cell carcinoma.
AB  - Cellular homeostasis in many organs is maintained via gap junctions composed of
      connexin (Cx), a large protein family with a number of isoforms. In fact, gap
      junctional intercellular communication (GJIC) is actively involved in all aspects
      of the cellular life cycle, ranging from cell growth to cell death. It has been
      well known that Cx gene acts as a tumor suppressor gene due to the maintenance of
      cellular homeostasis via GJIC. On the other hand, recent data show that GJIC
      independent function for Cx gene contributes to tumor-suppressive effect of the
      gene with cell certain specificity. However, the mechanistic aspect of the GJIC
      independent function remains largely unknown. In this review, we briefly
      summarize the tumor-suppressive effects of Cx genes, refer to a new aspect of
      Cx32 as an anti-invasive and anti-metastatic gene against renal cell carcinoma in
      a GJIC-independent function and establishment of a new cancer therapy based on
      the new function of Cx32.

PMID- 17015939
TI  - Differential activation of glucose transport in cultured muscle cells by
      polyphenolic compounds from Canna indica L. Root.
AB  - Effects of extracts of a plant, which has been used as a traditional medicine for
      treating diabetes on glucose transport activity was evaluated in cultured L8
      muscle cells. The aqueous extract of Canna indica root (CI) at doses of 0.1-0.5
      mg/ml, which contains total phenolic compounds equivalent to 6-30 microg of
      catechin caused a dose- and time-dependent induction of 2-deoxy-[3H]glucose (2
      DG) uptake activity. The induced 2-DG uptake was significantly increased within 8
      h and reached a maximum by 16 h. The CI extract increased the amount of glucose
      transporter isoforms 1 (GLUT1) and 4 (GLUT4) at the cell surface and enhanced
      expression of GLUT1 protein. Cycloheximide treatment almost completely reversed
      CI-induced 2-DG uptake to the basal level. Exposure of muscle cells to wortmannin
      and SB203580 diminished CI-mediated glucose uptake by 38 and 14%, respectively.
      The effect of CI and insulin was partially additive. Phytochemical analysis
      detected the presence of flavonoids and catechol in the CI. Taken together, these
      data provide evidence for differential effects of CI on regulated-glucose
      transport in muscle cells. Our findings suggest that GLUT1 protein synthesis and
      the activation of phosphatidylinositol 3-kinase (PI3K) are critical for the
      increase in glucose transporter activity at the plasma membrane and essential for
      the maximal induction of glucose transport by CI in L8 muscle cells.

PMID- 17015940
TI  - Anthracyclines, small-molecule inhibitors of hypoxia-inducible factor-1 alpha
      activation.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a central mediator of cellular responses to
      low oxygen and has recently become an important therapeutic target for solid
      tumor therapy. To identify small molecule inhibitors of the HIF-1 transcriptional
      activation, we have established a high through-put assay system using a stable
      transformant of mammalian cells that express the luciferase reporter gene
      construct containing a HIF-1 binding site. Using this system, we screened 5000
      cultured broths of microorganisms, and we found that cinerubin (1-hydroxy
      aclacinomycin B) showed a significant inhibition of the reporter activity induced
      by hypoxic conditions. In addition, we demonstrated that aclarubicin also
      inhibited the HIF-1 transcriptional activity under hypoxic conditions, but
      neither doxorubicin nor daunorubicin inhibited it. Consistent with these results,
      cinerubin and aclarubicin inhibited the hypoxic induction of the vascular
      endothelial growth factor (VEGF) protein in HepG2 cells, but neither doxorubicin
      nor daunorubicin affected it. Thus, our results suggested that some
      anthracyclines are also acting as angiogenesis inhibitors.

PMID- 17015941
TI  - Regulation of angiotensin II-Induced Kruppel-like factor 5 expression in vascular
      smooth muscle cells.
AB  - Angiotensin (Ang) II plays a critical role in cardiovascular remodeling. Kruppel
      like factor (KLF) 5 is a novel indicated mediator in Ang II-induced
      cardiovascular damage. However, the potential link between KLF5 and Ang II has
      not been well investigated. In this study, we showed that in growth-arrested
      vascular smooth muscle cells (VSMCs), Ang II induced cell proliferation, KLF5
      mRNA and protein expression in a dose- and time-dependent fashion, whereas KLF5
      mRNA stability was not affected. The AT1 antagonist losartan significantly
      blocked Ang II-induced KLF5 expression. Furthermore, several intracellular
      signals elicited by Ang II were involved in KLF5 gene upregulation, including
      phosphate tyrosine kinase, mitogen-activated protein kinases and reactive oxygen
      species. These data, for the first time, revealed the involvements of some
      intracellular signals in the regulation of KLF5 expression in response to Ang II
      in VSMCs and showed the possible role of KLF5 in Ang II-induced cell
      proliferation in VSMCs.

PMID- 17015942
TI  - In vivo evaluation of radioiodinated 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3
      phenylpropyl)-piperazine derivatives as new ligands for sigma receptor imaging
      using single photon emission computed tomography.
AB  - New series of radioiodinated analogues of 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-[3
      (2-iodophenyl)propyl]piperazine (o-BON) and 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-[3
      (3-iodophenyl)propyl]piperazine (m-BON) were evaluated as single photon emission
      computed tomography (SPECT) radiopharmaceuticals for mapping sigma receptors in
      the central nervous system (CNS) and peripheral organs. In vivo biodistribution
      studies of [125I] o- and m-BON in mice demonstrated high initial uptakes and
      prolonged retention in the brain. In contrast to high brain uptake and retention,
      the blood accumulations were low, resulting in good brain-blood ratios (7.9-9.2).
      In the other tissues, high uptake of [125I] o- and m-BON were observed in the
      liver, kidney, heart, lung, and pancreas. Moreover, selective interactions of
      [125I] o- and m-BON with sigma receptors were confirmed by pretreatment
      experiments with various sigma and other receptor ligands. Haloperidol
      posttreatment induced decreases in the accumulation of [125I] o- and m-BON. These
      data suggest that [125I] o- and m-BON binding to sigma receptors is reversible
      and competitive. Furthermore, ex vivo autoradiograms of [125I] o- and m-BON in
      rats showed high uptake in the parietal cortex, vestibular nucleus, and pons
      nucleus and moderate uptake in the thalamus, inferior colliculus, hippocampus,
      hypothalamus, and temporal cortex. These ex vivo autoradiograms were comparable
      with the histochemical distribution of sigma receptors. Furthermore, the uptake
      of [125I] o- and m-BON reflected quantitative amounts of sigma receptor in the
      brain. These results demonstrated that radiolabeled o- and m-BON have good
      characteristics for mapping sigma receptors in the CNS and the peripheral organs
      with SPECT.

PMID- 17015943
TI  - Involvement of oxidative stress in the synthesis of metallothionein induced by
      mitochondrial inhibitors.
AB  - We previously reported that synthesis of metallothionein (MT) was induced by
      mitochondrial inhibitors such as 2,4-dinitrophenol (DNP) or antimycin A (Kondoh
      et al., 2001), which are potent inhibitors of mitochondrial respiration. Although
      the inhibitors are known to be radical generators in mitochondria, the
      involvement of oxidative stress in the synthesis of MT induced by mitochondrial
      inhibitors and the biological functions of MT remain obscure. In this study,
      therefore, we examined the involvement of oxidative stress in MT synthesis
      induced by mitochondrial inhibitors and the biological functions of MT. In
      cultured mouse fibroblast cells, the addition of DNP increased both MT
      concentration and MT mRNA level. Administration of DNP to L-buthionine-SR
      sulfoximine (BSO)-pretreated mice increased hepatic lipid peroxidation and
      induction of MT synthesis. In addition, vitamin E prevented induction of MT
      synthesis as well as lipid peroxidation in the liver of mice caused by
      administration of DNP. Administration of mitochondrial inhibitor to mice elevated
      the levels of lipid peroxidation in the liver and mitochondria, and MT in the
      liver, indicating the generation of mitochondrial oxidative stress. These data
      suggest that the induction of MT synthesis by mitochondrial inhibitors is
      correlated with generation of oxidative stress in mitochondria. Furthermore, the
      level of DNP-induced alanine aminotransferase (ALT) activity, reflecting hepatic
      damage, was greater in MT-null mice than in wild-type mice, and intracellular
      accumulation of reactive oxygen species (ROS) caused by the action of
      mitochondrial inhibitors was greater in MT-null fibloblast cells than in wild
      type cells. The results suggest that MT plays a role as a radical scavenger of
      intracellular ROS produced in mitochondria. Taken together, the results suggest
      that mitochondrial oxidative stress induces the synthesis of MT, which may
      contribute to regulation of mitochondrial ROS production.

PMID- 17015944
TI  - Neuroprotective effect of some plant extracts in cultured CT105-induced PC12
      cells.
AB  - Carboxyl-terminal fragments of APP (CT) have been found in plaques, microvessels
      and the neurofibrillary tangles in the brains of AD patients. These carboxyl
      terminal fragments, which contain the complete Abeta sequence, appear to be toxic
      to neurons in culture cells. However, the possible role of other cleaved products
      of APP is less clear. We showed that a recombinant carboxy-terminal 105 amino
      acid fragment (CT105) of APP induced strong neurotoxicity in PC12 cells. We
      prepared alcoholic extract from Oriental herbal plants and screened their
      protective effects against CT105-induced cell death in PC12 cells after the
      treatment of these extracts. Of the 10 kinds of plant extracts, 12 kinds of
      extracts had considerable protective effects against CT105-induced cell death,
      especially, Uncariae Ramulus et Uncus (UREU), Gastrodia elata (GAE), Evodia
      officinalis (EO) and Panax ginseng (PAG) showed the most protective effect at the
      concentration of 50 microg/ml. BuOH extract of UREU and GAE possessed the
      strongest protective effects against neurotoxicity of CT105-induced PC12 cells
      and showed inhibitory effect with IC50 values of 4.8 and 8.3 microg/ml,
      respectively. These plants are promising candidates of neuroprotective effects
      and would be useful for the treatment of the neuronal degenerative diseases such
      as Alzheimer's diseases.

PMID- 17015945
TI  - Lymphtoxin beta receptor-Ig protects from T-cell-mediated liver injury in mice
      through blocking LIGHT/HVEM signaling.
AB  - LIGHT is a member of the TNF superfamily, which is transiently expressed on the
      surface of activated T lymphocytes and immature dendritic cells. Its known
      receptors are herpesvirus entry mediator (HVEM) prominently in T lymphocytes, and
      lymphtoxin beta receptor (LTbetaR) in stromal cells or nonlymphoid hematopoietic
      cells. Previous studies have shown that overexpression of LIGHT on T cells could
      lead to autoimmune reaction including lymphocytes activation, inflammation, and
      tissue destruction. To address the role of LIGHT/HVEM signaling in autoimmune
      hepatitis, an experimental colitis model induced by intravenous administration of
      concanavalin A (ConA) was given a soluble LTbetaR-Ig fusion protein as a
      competitive inhibitor of LIGHT/HVEM pathway. Marked elevation of LIGHT expression
      was detected in isolate intrahepatic leukocytes (IHLs) of the experimental
      animal. Treatment with LTbetaR-Ig significantly attenuated the progression and
      histological manifestations of the hepatic inflammation and reduced the
      production of inflammatory cytokines including TNF-alpha, IFN-gamma. Moreover,
      LTbetaR-Ig treatment significantly down-regulated LIGHT expression, leading to
      reduced lymphocytes (particularly CD4+ T cells), infiltrating into the hepatic
      inflammation and inhibited NF-kappaB activation and expression. We postulated
      that blockade of LIGHT/HVEM signaling by LTbetaR-Ig may ameliorate hepatitis by
      down-regulating LIGHT expression, and therefore we envision that LTbetaR-Ig would
      prove to a promising strategy for the clinical treatment of human autoimmune
      hepatitis.

PMID- 17015947
TI  - Epileptogenic activity of methicillin-resistant Staphylococcus aureus (MRSA)
      antibiotics in rats.
AB  - The present study was undertaken to clarify the epileptogenic activity induced by
      intracerebroventricular injection (i.c.v.) of antibiotics effective in
      methicillin-resistant Staphylococcus aureus (MRSA) in chronically electrode
      implanted rats. Teicoplanin (10-100 microg, i.c.v.) caused dose-related
      electroencephalographic (EEG) seizure characterized by an uninterrupted high
      voltage and wave complex. At the same time, the rats showed forelimb clonus, head
      nodding, jumping and severe convulsion. At a high dose (100 microg, i.c.v.), the
      drug caused a severe twisting immediately after the intracerebroventricular
      injection (i.c.v.) followed by jumping and violent convulsion with a continuous
      rhythmic spike and wave complex in EEG. On the other hand, vancomycin (30-1000
      microg, i.c.v.) caused no or almost no epileptogenic activity in terms of
      behavior and in EEG. However, at a high dose (1000 microg, i.c.v.), the drug
      caused an occasional spike from the hippocampus without showing any behavioral
      changes in the rats. Fosfomycin (30-1000 microg, i.c.v.), cefazolin (10-100
      microg, i.c.v.) and penicillin G (30-300 microg, i.c.v.), used as reference
      drugs, caused dose-dependent epileptogenic activity in both EEG. From these
      findings, it was found that teicoplanin caused a potent epileptogenic activity,
      different to vancomycin. Therefore, it can be concluded that vancomycin may be
      safety on epileptogenic activity used for the clinical purpose of infections
      caused by MRSA.

PMID- 17015946
TI  - In vitro and in vivo activities of HQQ-3, a new triazole antifungal agent.
AB  - The activity of HQQ-3, a new triazole antifungal agent, was evaluated and
      compared with those of fluconazole, ketoconazole and terbinafine in vitro and
      with fluconazole in vivo. HQQ-3 exhibited potent in vitro activity against
      clinically important fungi. The activity of HQQ-3 against Candida spp. was
      superior to those of fluconazole and terbinafine and comparable or superior to
      that of ketoconazole. HQQ-3 retained potent activity against Candida albicans
      strains with low levels of susceptibility to fluconazole (fluconazole MIC80s
      range, 4 to >64 microg/ml). Against Cryptococcus neoformans and filamentous
      fungi, the activity of HQQ-3 was superior to that of fluconazole. HQQ-3 also
      exhibited potent in vivo activity against murine systemic infections caused by C.
      albicns and C. krusei. The 50% effective doses against these infections were 0.12
      to 1.9 mg/kg of body weight. These result suggest that HQQ-3 may be useful in the
      treatment of candidiasis.

PMID- 17015948
TI  - Butyrate induces necrotic cell death in murine colonic epithelial cell MCE301.
AB  - Recent findings have suggested that organic acids produced by anaerobic
      intestinal bacteria might contribute to the pathogenesis of colonic ulcers. In
      this study, it was shown that butyrate caused potent cytotoxicity in the murine
      normal colonic epithelial cells MCE301 at physiological concentrations. Several
      markers of apoptosis, such as phosphatidyl serine externalization, cytochrome c
      release, DNA fragmentation, and chromatin condensation were negative after
      butyrate exposure. Inhibitor of caspases failed to protect against butyrate
      cytotoxicity. By transmission electron microscopy, marked swollen mitochondria
      and vacuolization within the cytoplasm was observed by treatment of butyrate.
      Collective, these data indicated that butyrate-induced cell death caused through
      a necrosis-like process. Butyrate induced cell death was reduced partially by
      treatment with prednisolone or 5-aminosalicylates in a concentration dependent
      manner. These results suggest that (1) butyrate induces necrotic cell death but
      not apoptotic cell death, and (2) the necrotic cell death induced by butyrate may
      be useful as a novel in vitro model of ulcerative colitis to screen useful drugs
      for the treatment of the disease.

PMID- 17015949
TI  - Hypoglycemic effects of multiflorine derivatives in normal mice.
AB  - (-)-Multiflorine isolated from leguminous plants produces a hypoglycemic effect
      when administered to mice with streptozotocin-induced diabetes. (-)-Multiflorine
      has an enaminone-type conjugation on the A ring, which is unusual in lupine
      alkaloids. Proceeding on the assumption that the A-B ring is responsible for the
      hypoglycemic effect, several compounds bearing the quinolizidin-2-one ring system
      were synthesized, and their hypoglycemic effects were examined. In addition,
      tricyclic compounds bearing 4-pyridone were synthesized, and their hypoglycemic
      effects were examined. The hypoglycemic effect of a 4-pyridone-type compound was
      similar to that of (-)-multiflorine as measured by oral glucose tolerance testing
      in normal mice. No hypoglycemic effect of a 4-piperidone-type compound was
      observed. These results indicate that compounds possessing double bond(s) in the
      A ring of multiflorine may be lead compounds for a new type of diabetes drug.

PMID- 17015950
TI  - Reduction of Cisplatin-induced nephrotoxicity by ginsenosides isolated from
      processed ginseng in cultured renal tubular cells.
AB  - Ginsenosides, the unique constituents and secondary metabolites of the Panax
      species, have been known to be the pharmacologically active ingredients of
      ginseng. Recently, our research group has developed a new processed ginseng,
      called Sun ginseng (SG), which has an increased amount of the red ginseng unique
      ginsenosides (RGUG). In our previous studies, this new processed ginseng reduced
      cisplatin-induced nephrotoxicity more than white ginseng in both in vitro and in
      vivo systems. In this study, we isolated and characterized active principles
      through activity-guided fractionation. Ginsenosides Rh4 and Rk3 significantly
      reduced the cisplatin-induced nephrotoxicity in LLC-PK1 cells in a dose-dependent
      manner. The mechanisms of function and structure-activity relationships with
      other ginsenosides remain for further investigation.

PMID- 17015951
TI  - Comparative chemical composition and antioxidant activities of wild and
      cultivated Laurus nobilis L. leaves and Foeniculum vulgare subsp. piperitum
      (Ucria) coutinho seeds.
AB  - The chemical composition and antioxidant activities of wild and cultivated Laurus
      nobilis leaves and Foeniculum vulgare subsp. piperitum seeds were determined.
      Differences were found in the total phenolic content of fennel. GC-MS analysis of
      the non polar fractions showed a different composition between wild and
      cultivated plants. Cultivated laurel had a high content of terpenes such as
      linool, alpha-terpinol, alpha-terpinyl acetate, thymol, caryophyllene,
      aromandrene, selinene, farnesene, and cadinene, while wild laurel had a high
      content of eugenol and methyl eugenol, vitamin E, and sterols. The antioxidant
      potential of the extracts was determined using three complementary methods. Wild
      plants showed greater radical scavenging activity than the cultivated plants. The
      extracts also exhibited a significant antioxidant capacity also in the beta
      carotene-linoleic acid test system. A high level of antioxidant activity was
      observed in wild laurel (IC50 = 1 microg/ml). Significant antioxidant activity
      measured in bovine brain was observed in wild laurel.

PMID- 17015952
TI  - Does a kampo medicine containing schisandra fruit affect pharmacokinetics of
      nifedipine like grapefruit juice?
AB  - Herb-drug interaction has attracted attention as medicinal topics recently.
      However, the drug information is sometimes confusing. Previous in vitro studies
      revealed that schisandra fruit had strong inhibitory effect on CYP3A4 and claimed
      the possibilities of its herb-drug interaction. In the present study, we
      evaluated the inhibitory effects of schisandra fruit and shoseiryuto, an herbal
      formula in Japanese traditional kampo medicine containing eight herbal medicines
      including schisandra fruit, on rat CYP3A activity in vitro, and the effect of
      shoseiryuto on pharmacokinetics of nifedipine in rats, in comparison with those
      of grapefruit juice, a well-characterized natural CYP3A inhibitor. Shoseiryuto
      and its herbal constituents, schisandra fruit, ephedra herb and cinnamon bark
      exhibited in vitro inhibitory effect of CYP3A. Although shoseiryuto inhibited rat
      CYP3A activity in vitro with a degree comparable to grapefruit juice, shoseiryuto
      did not significantly affect a plasma concentration profile of nifedipine in rats
      as grapefruit juice did. These results indicate that in vivo experiments using
      the extract of herbal medicine prepared with the same dosage form as patients
      take are necessary to provide proper information about herb-drug interaction.

PMID- 17015953
TI  - Induction of apoptosis in tumor cells by three naphthoquinone esters isolated
      from Thai medicinal plant: Rhinacanthus nasutus KURZ.
AB  - Rhinacanthus nasutus KURZ. (Acanthaceae) has been used as Thai traditional
      medicine for the treatment of various cancers. Recently, we reported that
      rhinacanthins, active components of the plant, had antiproliferative activity
      against human cancer line cells. In the present study, we investigated the growth
      inhibitory mechanism of rhinacanthins-C, -N and -Q, three main naphthoquinone
      esters isolated from the roots of R. nasutus KURZ. in human cervical carcinoma
      (HeLaS3) cells by means of TUNEL staining, DNA fragmentation assay, flow
      cytometry, and cleavage assay of Asp-Glu-Val-Asp-peptide-nitroanilide, a caspase
      3 substrate. After the HeLaS3 cells was exposed with different concentrations of
      the drugs, rhinacanthins-C, -N and -Q exhibited antiproliferative effects on
      HeLaS3 cells with the IC50 values of 80, 65, 73 microM; 55, 45, 55 microM; and
      1.5, 1.5 and 5.0 microM for 24, 48 and 72 h time points, respectively.
      Morphological changes showing nuclear fragmentation of rhinacanthins-treated
      cells were clearly observed after 48 h exposure. Consistent with this
      observation, the appearance of a ladder formation was also evident with an
      agarose gel electrophoresis of the extracted DNA. Flow cytometric analysis
      revealed that rhinacanthin-N caused G2/M arrest of HeLaS3 cells after 24 h
      incubation, and increased the proportion of sub-G1 hypodiploid cells, apoptotic
      cells, in the population of HeLaS3 cells after 48 and 72 h incubation. Moreover,
      the drug treatment markedly elevated the activity of caspase-3. Based on these
      results, our findings demonstrated for the first time that the inhibitory effects
      of three main naphthoquinone esters isolated from the roots of R. nasutus KURZ.
      on the growth of HeLaS3 cells appear to arise from the induction of apoptosis,
      that might be associated with the activation of caspase-3 pathway.

PMID- 17015954
TI  - Inhibitors of inducible nitric oxide synthase prevent damage to human lens
      epithelial cells induced by interferon-gamma and lipopolysaccharide.
AB  - We previously found that Ca2+ concentrations, inducible nitric oxide synthase
      (iNOS) mRNA, and protein expression in lenses of the Shumiya cataract rat (SCR)
      increase with the development of cataracts. In this study, we investigated the
      change in Ca2+-ATPase activities and ATP levels in the human lens epithelial cell
      line SRA 01/04 (HLE cells) with the stimulation of interferon-gamma (IFN-gamma)
      and lipopolysaccharide (LPS). Expression levels of iNOS mRNA in HLE cells, which
      were determined using semiquantitative reverse transcription-polymerase chain
      reaction (RT-PCR) and quantitative real-time RT-PCR methods, increased during
      stimulation with IFN-gamma (1000 IU) and LPS (100 ng/ml). NO release from HLE
      cells, expressed as the sum of NO2- and NO3- levels, increased with the increase
      in iNOS expression levels. Ca2+-ATPase activities increased and ATP levels
      decreased in HLE cells stimulated with the combination of IFN-gamma and LPS.
      Furthermore, both diethyldithiocarbamate and aminoguanidine attenuated the
      increase in Ca2+-ATPase activities and the decrease in ATP levels. These results
      suggest that excessive production of NO may cause mitochondrial damage, resulting
      in an increased Ca2+ concentration in the lens. The increase in Ca2+
      concentration in the lens may increase Ca2+-ATPase activities.

PMID- 17015955
TI  - Stomach-selective gene transfer following the administration of naked plasmid DNA
      onto the gastric serosal surface in mice.
AB  - The purpose of the present study was to achieve a stomach-selective gene transfer
      following the administration of naked plasmid DNA (pDNA) onto the gastric serosal
      surface in mice. Gene expression in the stomach and other tissues was evaluated
      by firefly luciferase activity. Six hours after gastric serosal surface
      instillation of naked pDNA, high gene expression in the stomach was observed. On
      the contrary, intravenous and intraperitoneal injection of naked pDNA exhibited
      no detectable gene expression. Following instillation of naked pDNA onto the
      gastric serosal surface, gene expression in the stomach was significantly higher
      than in other tissues. Gene expression in the stomach was highest 12 h after the
      instillation and thereafter decreased gradually. Utilizing a glass-made diffusion
      cell that is able to limit the contact dimension between the gastric serosal
      surface and the naked pDNA solution administered, site-specific gene expression
      in the stomach was achieved. This novel gene transfer method is expected to be a
      safe and effective treatment against serious stomach diseases.

PMID- 17015956
TI  - Radiosynthesis and evaluation of 11C-labeled diaryl-substituted imidazole and
      indole derivatives for mapping cyclooxygenase-2.
AB  - 11C-labeled analogs of 4-chloro-5-(3-fluoro-4-methoxyphenyl)-1-(4
      methylsulfonylphenyl)imidazole ([11C]1), 4-[4-chloro-5-(3-fluoro-4
      methoxyphenyl)imidazol-1-yl]benzenesulfonamide ([11C]2) and 2-(4
      aminosulfonylphenyl)-3-(4-methoxyphenyl)indole ([11C]3), which have been shown to
      have excellent potency and high selectivity for cyclooxygenase isoform 2 (COX-2)
      inhibiting activity, were prepared and evaluated in rats as potential
      radiopharmaceuticals for imaging the COX-2 enzyme by positron emission
      tomography. These 11C-labeled COX-2 inhibitors were synthesized in high
      radiochemical yields by O-[11C]methylation of phenolic precursors with
      [11C]methyl triflate in acetone containing NaOH as a base. In vivo evaluation in
      rats bearing AH109A hepatoma showed no specific binding of any tracer to COX-2 in
      any tissue such as the brain, heart, lung, kidney, and AH109A hepatoma. In ex
      vivo autoradiography, [11C]1 showed regionally different distribution in the
      brain, while [11C]2 and [11C]3 were not substantially taken up by the brain. In
      in vitro monolayer efflux assays, compound 3 was found to be a substrate for the
      P-glycoprotein (P-gp) efflux pump, but pretreatment of rats with the potent P-gp
      inhibitor, cyclosporine A, did not have any significant influence on the cerebral
      uptake of [11C]3. These results indicate that all three tracers were not suitable
      for in vivo imaging of COX-2. There seem to be some obstacles to finding a useful
      candidate for in vivo imaging application of COX-2 selective inhibitors only by
      standard consideration of in vitro affinity and selectivity, and the
      lipophilicity of the compound.

PMID- 17015957
TI  - Infliximab neutralizes the suppressive effect of TNF-alpha on expression of
      extracellular-superoxide dismutase in vitro.
AB  - Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in blood
      vessel walls, normal cartilage and synovial fluid and may be important for the
      antioxidant capability of these tissues. We have reported that EC-SOD gene
      transferred mice exhibited significant suppression of clinical symptoms of type
      II collagen induced arthritis [Iyama, et al., Arthritis Rheum., 44, 2160-2167
      (2001)] and plasma EC-SOD levels in type 2 diabetic patients were significantly
      negatively related to indices of insulin resistance [Adachi, et al., J.
      Endocrinol., 181, 413-417 (2004)]. Tumor necrosis factor-alpha (TNF-alpha) has
      been implicated in the pathological conditions of the above diseases and is a
      major therapeutic target, based on clinical studies with anti-TNF-alpha
      monoclonal antibodies such as infliximab. In this report, we investigated the
      effect of TNF-alpha on the expression of EC-SOD in cultured cells and the
      cooperating effect of infliximab. In the in vitro assays examined, expression of
      EC-SOD, but not other SOD isozymes, in smooth muscle and fibroblast cells were
      suppressed by the addition of TNF-alpha. Simultaneous addition of infliximab dose
      dependently and significantly prevented the suppressive effects of TNF-alpha. p38
      mitogen-activated protein kinase (MAPK) inhibitor, SB203580, prevented
      significantly the suppressive effect of TNF-alpha suggesting that p38 MAPK is an
      important signaling molecule downstream of TNF-alpha to inhibit the EC-SOD
      expression. From the results, it is speculated that the decline in TNF-alpha
      activity by the administration of infliximab results in the liberation of EC-SOD
      from the suppressed state of gene expression. This reveals a potential usefulness
      of infliximab on TNF-alpha related pathological conditions such as arthritis and
      insulin resistance.

PMID- 17015958
TI  - Clinical pharmacokinetics of mycophenolate mofetil in Japanese renal transplant
      recipients: A retrospective cohort study in a single center.
AB  - Mycophenolate mofetil (MMF), a morpholinoethyl ester of mycophenolic acid (MPA),
      is currently widely used in organ transplantation as an immunosuppressant. The
      usefulness of therapeutic drug monitoring (TDM) of MPA after MMF dosing is not
      clear in Japanese renal transplant patients. In this study, to obtain more
      information for TDM of MPA, the association between MPA pharmacokinetic
      characteristics and the development of the side effects, and the effect of other
      concomitant immunosupressants such as cyclospoline A (CyA), tacrolimus (FK) and
      predonisolone (PSL) on MPA pharmacokinetics were investigated in detail.
      Moreover, the effects of enterohepatic recirculation (EHRA) on pharmacokinetic
      characteristics of MPA and the development of the side effects were also
      investigated. AUC(MPA)(0-9) with FK medication was 1.3-1.9 times higher than that
      with CyA medication, and the contribution to the plasma level of MPA of FK might
      be smaller than that of CyA, because EHRA inhibition by CyA was 2 times greater
      than that by FK. AUC(MPA)(0-9) was not influenced by PSL. The association between
      AUC(MPA)(0-9) and the development of the side effects was not observed; however,
      the development of side effects (leukopenia and diarrhea) in the EHRA group was 2
      times higher than that in the non-EHRA group. These results suggested that TDM
      for MPA after MMF dosing was desirable in Japanease transplant patients. However,
      though not frequently, AUC obtained by multiple blood sampling after MMF dosing
      was needed. In addition, EHRA has led to increasing interest in MMF medication.

PMID- 17015959
TI  - Effects of astaxanthin supplementation on exercise-induced fatigue in mice.
AB  - The present study was designed to determine the effect of astaxanthin on
      endurance capacity in male mice aged 4 weeks. Mice were given orally either
      vehicle or astaxanthin (1.2, 6, or 30 mg/kg body weight) by stomach intubation
      for 5 weeks. The astaxanthin group showed a significant increase in swimming time
      to exhaustion as compared to the control group. Blood lactate concentration in
      the astaxanthin groups was significantly lower than in the control group. In the
      control group, plasma non-esterfied fatty acid (NEFA) and plasma glucose were
      decreased by swimming exercise, but in the astaxanthin group, NEFA and plasma
      glucose were significantly higher than in the control group. Astaxanthin
      treatment also significantly decreased fat accumulation. These results suggest
      that improvement in swimming endurance by the administration of astaxanthin is
      caused by an increase in utilization of fatty acids as an energy source.

PMID- 17015961
TI  - Change of estrogenic activity and release of chloride ion in chlorinated
      bisphenol a after exposure to ultraviolet B.
AB  - Bisphenol A (BPA) and chlorinated bisphenol A (ClBPAs) were detected in
      wastewater from waste paper recycling plants. In previous study, we showed the
      acute cytotoxicity of oxidized products of BPA and ClBPAs generated by
      ultraviolet (UV) irradiation. However, estrogenic activities of these
      photoproducts have not been studied. Therefore, we investigated change of
      estrogenic activities of BPA and ClBPAs [3-chlorobisphenol A (3-ClBPA), 3,3'
      dichlorobisphenol A (3,3'-diClBPA) and 3,3',5-trichlorobisphenol A (3,3',5
      triClBPA)] after UVB irradiation using yeast two-hybrid assay. The agonist
      activities of ClBPAs were higher than that of BPA in the absence of S9. ClBPAs
      irradiated with UVB lost agonist activities. The addition of S9 also completely
      erased the activity. The antagonist activities of BPA and ClBPAs with or without
      UVB irradiation were not detected both in the absence or presence of S9. UVB
      irradiation (0-100 J/cm2) decreased the agonist activity of 3,3'-diClBPA in
      proportion to increase of released chloride ion. The agonist activity was
      completely lost at 50 J/cm2 of UVB, of which dose could dissociated almost all
      chlorine. These findings suggested that UVB irradiation could decrease the
      estrogenic activity of chlorinated compounds, which was due to the selective
      release of chloride ion.

PMID- 17015960
TI  - Effects of pine needle extract on differentiation of 3T3-L1 preadipocytes and
      obesity in high-fat diet fed rats.
AB  - The present study examined the anti-obesity effects of pine needle extract (PNE)
      in 3T3-L1 preadipocytes and in vivo studies. PNE treatment suppressed both
      glycerol-3-phosphate dehydrogenase activity and expression of peroxisome
      proliferator-activated receptor (PPAR) gamma in cultured 3T3-L1 adipocytes. To
      investigate the effect of PNE on obesity in rats fed high-fat diet, four types of
      diet, which included a normal diet (ND), high-fat diet (HFD), ND+PNE, and HFD+PNE
      diets, were fed to the rats ad libitum for 6 weeks. The PNE supplement
      significantly decreased body weight gain and visceral fat mass compared to the
      HFD group. The total cholesterol, TG, and leptin levels in the plasma were
      significantly reduced by PNE supplementation compared with those of the HFD
      group. Histological findings in liver tissue showed that PNE supplementation
      alleviated steatosis induced by HFD. In conclusion, PNE treatment suppressed
      differentiation of 3T-L1 adipocytes, in part by down-regulating expression of
      PPAPgamma mRNA, and reduced adipose tissue mass, hyperlipidemia, and hepatic
      steatosis in obese rats fed HFD. Therefore, pine needle water extract may be
      considered for use in therapy to control obesity.

PMID- 17015962
TI  - Effects of possible endocrine disrupting chemicals on bacterial component-induced
      activation of NF-kappaB.
AB  - Endocrine disrupting chemicals (EDCs) have a possibility to exacerbate infectious
      diseases because EDCs disturb the human immune system by interfering with
      endocrine balance. To assess the influence of EDCs on the innate immune function
      of macrophages, we investigated the effects of thirty-seven possible endocrine
      disruptors on lipopolysaccharide (LPS)- or bacterial lipopeptide (Pam3CSK4)
      induced activation of nuclear factor kappa B (NF-kappaB). Alachlor, benomyl,
      bisphenol A, carbaryl, kelthane, kepone, octachlorostyrene, pentachlorophenol,
      nonyl phenol, p-octylphenol and ziram inhibited both LPS- and Pam3CSK4-induced
      activation of NF-kappaB. Simazine inhibited only LPS-induced activation. A strong
      inhibitory effect was observed with ziram and benomyl. On the other hand,
      diethylhexyl adipate and 4-nitrotoluene tended to enhance the activation induced
      by Pam3CSK4 and LPS, respectively. Aldicarb, amitrole, atrazine, benzophenone,
      butyl benzyl phthalate, 2,4-dichlorophenoxy acetic acid, dibutyl phthalate, 2,4
      dichlorophenol, dicyclohexyl phthalate, diethylhexyl phthalate, diethyl
      phthalate, dihexyl phthalate, di-n-pentyl phthalate, dipropyl phthalate,
      malathion, methomyl, methoxychlor, metribuzin, nitrofen, permethrin, trifluralin,
      2,4,5-trichlorophenoxyacetic acid and vinclozolin had no significant effects at
      100 microM. These results indicate that some agrochemicals have the potential to
      inhibit macrophage function and suggest that endocrine disruptors may influence
      the development of bacterial infections.

PMID- 17015963
TI  - Characterization of the disposition of lutein after i.v. administration to rats.
AB  - Lutein is a carotenoid that has antioxidant effects. Although lutein has received
      much attention recently due to its antioxidant activities, little information
      about the pharmacokinetic properties of lutein is available. The disposition of
      lutein after i.v. administration has not been investigated because lutein is now
      used as a supplement. The present study was undertaken to acquire additional data
      on the disposition of lutein after i.v. administration. After i.v.
      administration, lutein is preferentially distributed to the liver, spleen and
      lung. Intravenous administration of lutein may provide effective antioxidant
      activities in these tissues, not only the eye. The results of this study should
      provide valuable data for drug development.

PMID- 17015964
TI  - Activity of neolignans isolated from Piper regnellii (MIQ.) C. DC. var.
      pallescens (C. DC.) YUNCK against Trypanosoma cruzi.
AB  - The in vitro antiproliferative effects of 4 neolignans purified from the ethyl
      acetate extract from leaves of Piper regnellii (MIQ.) C. DC. var. pallescens (C.
      DC.) YUNCK against Trypanosoma cruzi were investigated. These isolated compounds
      were identified through spectral analyses of UV, EI-MS, 1H-, 13C-NMR, H-H COSY,
      gNOE, HETCOR, and HMBC. The compounds eupomatenoid-5, eupomatenoid-6, and
      conocarpan showed considerable activity against epimastigote forms of T. cruzi,
      with 50% inhibition concentrations (IC50) of 7.0, 7.5, and 8.0 microg/ml
      respectively. After methylation, these compounds showed a lessened inhibitory
      activity to the growth of the protozoan, suggesting that loss of the hydroxyl
      group from their molecules reduces the activity. The compound eupomatenoid-3
      showed lower activity than the hexane fraction. Eupomatenoid-5 was significantly
      more active than benznidazole, the antiparasitic drug of choice for treatment of
      Chagas' disease. The crude extract, hexane fraction, and eupomatenoid-5 caused no
      lysis in sheep blood at concentrations which inhibit the growth of epimastigote
      forms. The compound eupomatenoid-5 showed low cytotoxic effects against Vero
      cells. These results provide new perspectives on the development of novel drugs
      obtained from natural products with trypanocidal activity. However, the extracts
      and active compound isolated from P. regnellii var. pallescens should be further
      studied in animal models for in vivo efficacy.

PMID- 17015965
TI  - In vitro antiviral activity of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose against
      hepatitis B virus.
AB  - This study examined the antiviral activity of the root of Paeonia lactiflora
      PALL. Among the solvent fractions of the crude drug, the ethyl acetate fraction
      showed anti-hepatitis B virus (HBV) activity (IC50, 8.1 microg/ml) in an HBV
      producing HepG2.2.15 cell culture system. The active anti-HBV principle was
      isolated and identified as 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) from
      the crude drug by activity-guided fractionation. PGG isolated from P. lactiflora
      was examined for the inhibition of HBV multiplication by measurement of HBV DNA
      and hepatitis B surface antigen (HBsAg) levels in the extracellular medium of
      HepG2.2.15 cells after 8-d treatment. PGG decreased the level of extracellular
      HBV (IC50, 1.0 microg/ml) in a dose-dependent manner. PGG also reduced the HBsAg
      level by 25% at a concentration of 4 microg/ml. The gallate structure of PGG may
      play a critical role in the inhibition of anti-HBV activity. These results
      suggest that PGG could be a candidate for developing an anti-HBV agent.

PMID- 17015966
TI  - Antiviral sulfated polysaccharide from Navicula directa, a diatom collected from
      deep-sea water in Toyama Bay.
AB  - A sulfated polysaccharide named naviculan was isolated from a diatom, Navicula
      directa (W. SMITH) RALFS, collected in deep sea water from Toyama Bay. The
      polysaccharide consisted of fucose, xylose, galactose, mannose, rhamnose and
      sulfate with an apparent molecular weight of 220000. It showed antiviral
      activities against herpes simplex viruses type 1 and 2, and influenza A virus
      with selectivity indices (CC50/IC50) of 270, 510 and 32, respectively. Naviculan
      also showed an inhibitory effect on cell-cell fusion between CD4-expressing and
      human immunodeficiency virus (HIV) gp160-expressing cells that was used as a
      model system of infection with HIV.

PMID- 17015967
TI  - Crinamine from Crinum asiaticum var. japonicum inhibits hypoxia inducible factor
      1 activity but not activity of hypoxia inducible factor-2.
AB  - In a search for natural product inhibitors of hypoxia inducible factor-1 (HIF-1)
      function, crinamine (1), a crinane type alkaloid, showed potent dose dependent
      inhibition (IC50 = 2.7 microM) of HIF-1alpha in a cell-based reporter gene assay.
      Crinamine (1) was isolated from the aerial parts of Crinum asiaticum var.
      japonicum together with lycorine (2), norgalanthamine (3) and epinorgalanthamine
      (4). The other components (2-4) showed no significant inhibition of HIF-1alpha
      induced transcriptional activity.

PMID- 17015968
TI  - Transport of timolol and tilisolol in rabbit corneal epithelium.
AB  - The purpose of this study is to characterize the transport of tilisolol and
      timolol through the corneal epithelium, which is believed to be a tight barrier
      of ocular drug absorption. Cultured normal rabbit corneal epithelial cells (RCEC)
      were used to investigate drug transport. Primary RCEC were seeded on a filter
      membrane of Transwell-COL insert coated with fibronectin and grown in Dulbecco's
      modified Eagle's medium/nutrient mixture F-12 with various supplements. Beta
      blocker permeability through the RCEC layer was measured to assess the
      transcellular permeability coefficient (P(transcell)) in the absence or presence
      of inhibitors. The transcellular permeability of tilisolol was dependent on drug
      concentration although timolol showed no concentration dependency. Tilisolol flux
      from the apical to the basal side was larger than in the opposite direction
      although timolol showed no direction dependency. The transcellular permeability
      of tilisolol from the apical to the basal side was inhibited by sodium azide,
      tetraethylammonium, quinidine, taurocholic acid, guanidine and carnitine.
      Tilisolol had an active mechanism in uptake to the corneal epithelium, probably
      by the organic cation transporter family, although timolol predominantly
      permeated via passive diffusion. This RCEC system was useful to characterize the
      ocular permeation mechanism of drugs.

PMID- 17015969
TI  - Inhibition of dehydroascorbic acid transport across the rat blood-retinal and 
      brain barriers in experimental diabetes.
AB  - Vitamin C is mainly transported across the blood-retinal and -brain barriers as
      dehydroascorbic acid (DHA) via a facilitative glucose transporter, GLUT1, and
      accumulates as ascorbic acid in the retina and brain. To investigate whether DHA
      transport to the retina and brain is changed by hyperglycemia, [14C]DHA transport
      across the blood-retinal and -brain barriers was examined using in vivo
      integration plot analysis in streptozotocin-induced diabetic rats with a 3-week
      duration of diabetes and in normal rats. Blood-to-retina and -brain transport of
      [14C]DHA was reduced by 65.5% and 84.1%, respectively, in diabetic rats compared
      with normal rats, whereas there was no major difference in the heart. Therefore,
      we propose that hyperglycemia reduces the supply of vitamin C to the retina and
      brain.

PMID- 17015970
TI  - Acid-base catalysis of chiral Pd complexes: development of novel catalytic
      asymmetric reactions and their application to synthesis of drug candidates.
AB  - Using the unique character of the chiral Pd complexes 1 and 2, highly efficient
      catalytic asymmetric reactions have been developed. In contrast to conventional
      Pd(0)-catalyzed reactions, these complexes function as an acid-base catalyst.
      Thus active methine and methylene compounds were activated to form chiral
      palladium enolates, which underwent enantioselective carbon-carbon bond-forming
      reactions such as Michael reaction and Mannich-type reaction with up to 99% ee.
      Interestingly, these palladium enolates acted cooperatively with a strong protic
      acid, formed concomitantly during the formation of the enolates to activate
      electrophiles, thereby promoting the C-C bond-forming reaction. This palladium
      enolate chemistry was also applicable to electrophilic enantioselective
      fluorination reactions, and various carbonyl compounds including beta-ketoesters,
      beta-ketophosphonates, tert-butoxycarbonyl lactone/lactams, cyanoesters, and
      oxindole derivatives could be fluorinated in a highly enantioselective manner (up
      to 99% ee). Using this method, the catalytic enantioselective synthesis of BMS
      204352, a promising anti-stroke agent, was achieved. In addition, the direct
      enantioselective conjugate addition of aromatic and aliphatic amines to
      alpha,beta-unsaturated carbonyl compound was successfully demonstrated. In this
      reaction, combined use of the Pd complex 2 having basic character and the amine
      salt was the key to success, allowing controlled generation of the nucleophilic
      free amine. This aza-Michael reaction was successfully applied to asymmetric
      synthesis of the CETP inhibitor torcetrapib.

PMID- 17015971
TI  - Acyclic diterpene glycosides, capsianosides VIII, IX, X, XIII, XV and XVI from
      the fruits of Paprika Capsicum annuum L. var. grossum BAILEY and Jalapeno
      Capsicum annuum L. var. annuum.
AB  - Paprika and Jalapeno are used as vegetables and spices. We have obtained six new
      acyclic diterpene glycosides, called capsianosides XIII (2), XV (3), IX (4), XVI
      (5), X (6) and VIII (7) together with known capsianoside II (1) from the fruits
      of the Paprika and Jalapeno. The structures of these compounds have been
      elucidated by the (1)H- and (13)C-NMR spectra and two-dimensional NMR methods.

PMID- 17015972
TI  - Studies on Nepalese crude drugs. XXIX. Chemical constituents of Dronapuspi, the
      whole herb of Leucas cephalotes SPRENG.
AB  - From the whole herb of Leucas cephalotes SPRENG., new labdane-, norlabdane- and
      abietane-type diterpenes named leucasdins A (1), B (2) and C (3), respectively,
      and two protostane-type triterpenes named leucastrins A (4) and B (5) were
      isolated, together with a known triterpene, oleanolic acid, five sterols, 7
      oxositosterol, 7-oxostigmasterol, 7alpha-hydroxysitosterol, 7alpha
      hydroxystigmasterol and stigmasterol, and eight flavones, 5-hydroxy-7,4'
      dimethoxyflavone, pillion, gonzalitosin I, tricin, cosmosin, apigenin 7-O-beta-D
      (6-O-p-coumaroyl)glucopyranoside, anisofolin A and luteolin 4'-O-beta-D
      glucuronopyranoside. The structures of 1--5 were determined as
      (3S,6R,8R,9R,13S,16S)-9,13,15,16-bisepoxy-3,16-diacetoxy-6-formyloxylabdane,
      (3S,6R)-3-acetoxy-6-formyloxy-iso-ambreinolide, (4R,9S,12R,13R)-12,13
      dihydroxyabiet-7-en-18-oic acid, (3S,17S,20S,24S)-3,20-dihydroxy-24-methylprotost
      25-en, and (3S,17S,20S,24S)-3,20,24-trihydroxyprotost-25-en respectively, based
      on spectral and chemical data.

PMID- 17015973
TI  - Triterpenoid saponins from Lysimachia davurica.
AB  - Three new saponins were isolated from the whole plants of Lysimachia davurica. On
      the basis of 1D and 2D NMR ((1)H-(1)HCOSY, HMBC, HMQC, and TOCSY) techniques, MS,
      and hydrolysis, their structures were found to be 3-O-beta-D-glucopyranosyl-(1-
      >2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl-13,28-epoxy-3beta
      hydroxy-16-oleanaone (1), 3-O-beta-D-glucopyranosyloxyuronic acid-(1-->2)-beta-D
      xylopyranosyl-cyclamiretin A (2), and 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl-cyclamiretin A (3), respectively. Compounds 2 and 3 showed
      significant cytotoxicities against human A-2780 cells.

PMID- 17015974
TI  - Synthesis, biological evaluation and in silico metabolic and toxicity prediction
      of some flavanone derivatives.
AB  - Flavones chemically are anthoxanthins, occur either in the free state or as
      glycosides associated with tannins (flavanoids). Flavanoids (derivatives of
      flavone) possess various pharmacological activities and due to its xanthine
      oxidase enzyme inhibitory effect it also has superoxide-scavenging activities. A
      series of 2-phenyl-2,3-dihydrochromon-4-one derivatives (flavanone derivatives)
      were synthesized from chalcones by cyclization method and their activities were
      evaluated against some gram positive and gram-negative bacteria. IR, NMR and CHN
      analysis confirmed the structure of the synthesized compounds. The results of the
      antibacterial studies shows that compounds 2b, 2e, 2f and 2h possess activity
      against many bacterial strains. Among that the compound (2h) has remarkable
      activity against all strains viz. 25 microg/ml inhibitory concentration against
      S. aureus, S. sonnei, E. coli, S. typhimurium and V. cholerae. Compound 2f
      possess minimum inhibitory concentration of 200 microg/ml against E. coli and S.
      typhimurium and 25 microg/ml against S. sonnei, S. dysenteriae and V. cholerae.
      In silico metabolic and toxicity study of the synthesized compounds were
      performed and the predicted result showed that the compound having hydroxyl
      functional group undergo sulfate and O-glucuronide conjugation reaction and
      methoxy derivatives undergo demethylation reaction. The biologically active
      compounds are free of toxicity in oncogene, teratogen, sensitivity and
      immunotoxicity.

PMID- 17015976
TI  - Phosphorylation of D-glucose derivatives with inorganic monoimido-cyclo
      triphosphate.
AB  - Phosphorylation of several D-glucose derivatives has been achieved using
      inorganic monoimido-cyclo-triphosphate (MCTP, Na(3)P(3)O(8)NH) in aqueous
      solution. In the phosphorylation of D-glucose, D-glucuronic acid, 2-deoxy-D
      glucose and D-galactose, 1-O-diphosphoramidophosphono-beta-D-glucose, 1-O
      diphosphoramidophosphono-beta-D-glucuronic acid, 1-O-diphosphoramidophosphono-2
      deoxy-beta-D-glucose, and 1-O-diphosphoramidophosphono-beta-D-galactose were
      stereoselectively synthesized with yields of 54, 32, 37 and 46%, respectively. In
      the case of methyl alpha-D-glucoside, the phosphorylated products were methyl 3-O
      diphosphoramidophosphono-alpha-D-glucoside and methyl 4-O
      diphosphoramidophosphono-alpha-D-glucoside, and in the case of methyl beta-D
      glucoside the products were methyl 2-O-diphosphoramidophosphono-beta-D-glucoside,
      methyl 3-O-diphosphoramidophosphono-beta-D-glucoside, and methyl 4-O
      diphosphoramidophosphono-beta-D-glucoside. For D-mannose and D-allose, several
      phosphorylated products were obtained and the main products were 1-O
      diphosphoramidophosphono-beta-D-aldoses.

PMID- 17015977
TI  - Radical-scavenging activities of new megastigmane glucosides from Macaranga
      tanarius (L.) MULL.-ARG.
AB  - Four new megastigmane glucosides, named macarangiosides A-D (2-5), together with
      mallophenol B, lauroside E, methyl brevifolin carboxylate, and hyperin and
      isoquercitrin as a mixture were isolated from the leaves of Macaranga tanarius
      (L.) MULL.-ARG. (Euphorbiaceae). Their structures were elucidated by
      spectroscopic and chemical analyses. Macarangioside A-C (2-4) and mallophenol B
      were galloylated on glucose moiety and possessed the potent 2,2-diphenyl
      picrylhydrazyl (DPPH) radical-scavenging activity.

PMID- 17015975
TI  - A green method for the electroorganic synthesis of new 1,3-Indandione
      derivatives.
AB  - This is an environmentally friendly method in the field of electroorganic
      reactions under controlled potential electrolysis, without toxic reagents at a
      carbon electrode in an undivided cell which involves the (EC) mechanism reaction
      and comprises two steps alternatively; (i) electrochemical oxidation and (ii)
      chemical reaction. In particular, the electrochemical oxidation of 4-tert
      butylcatechol, 4-methylcatechol and 2,3-dihydroxybenzoic acid in the presence of
      2-phenyl-1,3-indandione has been studied in a water-acetonitrile (90 : 10)
      mixture. The research includes the use of a variety of experimental techniques,
      such as cyclic voltammetry, controlled-potential electrolysis, and spectroscopic
      identification of products (FT-IR, (1)H-NMR, and MS spectrometry).

PMID- 17015978
TI  - A practical and facile synthesis of azetidine derivatives for oral carbapenem, L
      084.
AB  - An orally active carbapenem L-084, which exhibits high bioavailability in humans,
      has a 1-(1,3-thiazolin-2-yl)azetidin-3-ylthio moiety at the C-2 position of the
      1beta-methylcarbapenem skeleton. We established a practical and cost-effective
      synthesis of 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (1) for further scale-up
      production of L-084. This synthesis method entails an industry-oriented reaction
      of azetidine ring-closure to yield N-benzyl-3-hydroxyazetidine (16), which is
      eventually converted to 1 via key intermediates, Bunte salts 19 and 20.

PMID- 17015979
TI  - Efficient ortho-oxidation of phenol and synthesis of anti-MRSA and anti-VRE
      compound abietaquinone methide from dehydroabietic acid.
AB  - A quinone methide diterpene: abietaquinone methide, which possesses potent anti
      methicillin-resistant Staphylococcus aureus (MRSA) and anti-vancomycin-resistant
      Enterococcus (VRE) activities, was synthesized via efficiently ortho-oxidation of
      ferruginol derived from industrially available dehydroabietic acid. ortho
      Oxidation of phenols was developed to give mono esters of catechols using a
      stable diacyl peroxide, bis(4-chlorobenzoyl) peroxide (m-chlorobenzoyl peroxide:
      mCBPO) which was synthesized from meta-chlorobenzoic acid. Efficient one pot
      ortho-oxidation reaction of phenol with an adduct of meta-chloroperbenzoic acid
      (mCPBA) with dicyclohexylcarbodiimide (DCC) was also reported.

PMID- 17015980
TI  - Synthesis and anti-HIV activity of novel cyclopentenyl nucleoside analogues of 8
      azapurine.
AB  - Novel nucleoside analogues of structure 3-5 were synthesized starting from (+/-)
      cis-2-amino-3-cyclopentenylmethanol (1). The chlorine derivative 3 inhibited both
      HIV-1 and HIV-2 replication in MT-4 cells with IC(50) values of 10.67 microM and
      of 13.79 microM, respectively.

PMID- 17015981
TI  - New iridoid glucosides from the aerial parts of Verbena brasiliensis.
AB  - Two new iridoid glucosides, verbenabraside A (1) and verbenabraside B (2), were
      isolated from the aerial parts of Verbena brasiliensis VELL., along with six
      known iridoid glucosides, gelsemiol 3-O-beta-D-glucoside (3), verbraside (4), 9
      hydroxysemperoside (5), griselinoside (6), aralidioside (7), and 6alpha
      hydroxyforsythide dimethyl ester (8), three known phenylethanoid glycosides, 2
      phenylethyl O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (9), acteoside
      (10), and leucosceptoside A (11), two known lignan glucosides, dihydroxymethyl
      bis(3,5-dimethoxy-4-hydroxyphenyl) tetrahydrofuran-9 (or 9')-O-beta
      glucopyranoside (12) and (+)-lyoniresinol 3alpha-O-beta-D-glucopyranoside (13), a
      known methyl salicylate glucoside, methyl 2-O-beta-D-glucopyranosylbenzoate (14),
      and two known sterols, beta-sitosterol 3-O-beta-D-glucopyranoside (15) and beta
      sitosterol (16). Their chemical structures were determined on the basis of
      spectroscopic data. Compound 1 exhibited stronger scavenging effect on the stable
      free radical 1,1-diphenyl-2-picrylhydrazyl than that of alpha-tocopherol.

PMID- 17015982
TI  - Cucurbitane glycosides from unripe fruits of Lo Han Kuo (Siraitia grosvenori).
AB  - From the unripe fruits of Lo Han Kuo (Siraitia grosvenori), a Chinese medicinal
      plant, two new cucurbitane triterpene glycosides, 20-hydroxy-11-oxomogroside
      IA(1) (1) and 11-oxomogroside IIE (2), were isolated along with five known
      cucurbitane glycosides, 11-oxomogroside IA(1) (3), mogroside IIE (4), mogroside
      III (5), mogroside IVA (6), and mogroside V (7), and two flavonoid glycosides,
      kaempferol 7-O-alpha-L-rhamnopyranoside (8) and kaempferol 3,7-di-O-alpha-L
      rhamnopyranoside (9). Their structures were determined on the basis of detailed
      analyses of 1D, 2D-NMR spectroscopic methods and by comparing with literature
      values. This paper describes the first investigation of unripe bitter Lo Han Kuo
      fruits.

PMID- 17015983
TI  - New labdane diterpenes from the stem bark of Larix laricina.
AB  - Two new labdane diterpenes, cis-19-hydroxyabienol (1) and 8alpha-hydroxy-12Z,14
      labdadien-19-al (2), along with another labdane described for the first time in
      the genus Larix, 19-acetoxy-13S-hydroxy-8(17),14-labdadiene (3) and a stilbene, 3
      methoxy-3,3',5'-trihydroxystilbene (4), were isolated from the stem bark of Larch
      (Larix laricina). Their structures were established by standard chemical and
      spectroscopic methods. Compounds 2 and 3 were shown to be moderately cytotoxic
      against A-549, DLD-1 and normal skin fibroblast cell lines, WS1. Compound 1 was
      found to be selectively active against colon carcinoma cell lines, DLD-1.

PMID- 17015984
TI  - Bioactive constituents of the root bark of Artocarpus rigidus subsp. rigidus.
AB  - Investigation of the chemical constituents of the root bark of Artocarpus rigidus
      BLUME subsp. rigidus has led to the isolation of six, structurally diverse
      phenolic compounds. These included two new compounds with modified skeletons, the
      flavonoid 7-demethylartonol E (1) and the chromone artorigidusin (2), together
      with four known phenolic compounds, the xanthone artonol B (3), the flavonoid
      artonin F (4), the flavonoid cycloartobiloxanthone (5), and the xanthone
      artoindonesianin C (6). Compounds 1, 4, and 5 exhibited antiplasmodial activity
      against Plasmodium falciparum. All compounds showed antimycobacterial activity
      against Mycobacterium tuberculosis, with 4 being the most active compound (MIC
      6.25 microg/ml). Compounds 5 and 6 were active against KB cells, whereas 2, 5,
      and 6 showed varying toxicity to BC cells. Compounds 1-3, 5, and 6 were active in
      the NCI-H187 cytotoxicity assay, with 3 being the most active compound (IC(50)
      1.26 microg/ml).

PMID- 17015985
TI  - Antimalarial activity of sesquiterpene lactones from Vernonia cinerea.
AB  - Two new sesquiterpene lactones, vernolides C and D as well as six known ones were
      isolated from the dichloromethane fraction of an aqueous extract from Vernonia
      cinerea. Their structures were elucidated by spectroscopic methods. Among the
      known sesquiterpene lactones, three of them were described in this plant for the
      first time. In vitro antiplasmodial evaluation showed that the three major
      compounds 1, 7 and 8 were active against chloroquine resistant Plasmodium
      falciparum strain (W2) with IC(50) 3.9, 3.7 and 3.5 microM, respectively.

PMID- 17015986
TI  - A pair of diastereoisomeric steroidal saponins from cytotoxic extracts of
      Tupistra chinensis rhizomes.
AB  - A pair of diastereoisomeric steroidal saponins were obtained from the saponin
      fraction (SF) of methanol extracts from Tupistra chinensis rhizomes, collected in
      Shennongjia Forest District, China. Based on the chemical and spectroscopic
      evidences, their structures were determined as shown in Fig. 1. The sample SF
      displayed marked inhibitory action in vitro towards HeLa and HL-60 cancer cell
      lines at 10 microg/ml by MTT method.

PMID- 17015987
TI  - Tirucallane-type triterpenoid saponins from the roots of Sapindus mukorossi.
AB  - Six new tirucallane-type triterpenoid saponins, sapimukosides E-J (1-6) were
      isolated from the roots of Sapindus mukorossi GAERTN. Their structures were
      elucidated by a combination of spectral and chemical analysis.

PMID- 17015988
TI  - Stability indicating methods for determination of Donepezil Hydrochloride
      according to ICH guidelines.
AB  - Stability indicating assays for determination of Donepezil Hydrochloride in
      presence of its oxidative degradate were developed and validated. The first three
      are spectrophotometric methods depending on using zero order (D(0)), first order
      (D(1)) and second order (D(2)) spectra. The absorbance was measured at 315 nm for
      (D(0)) while the amplitude was measured at 332.1nm for (D(1)) and 340 nm for
      (D(2)) using deionized water as a solvent. Donepezil Hydrochloride (I) can be
      determined in the presence of up to 70% of its oxidative degradate (II) using
      (D(0)), 80% using (D(1)) and 90% using (D(2)). The linearity range was found to
      be 8-56 microg ml(-1) for (D(0)), (D(1)) and (D(2)). These methods were applied
      for the analysis of I in both powder and tablet form. Also, a spectrofluorimetric
      method depending on measuring the native fluorescence of I in deionized water
      using lambda excitation 226 nm and lambda emission 391 nm is suggested. The
      linearity range was found to be 0.32-3.20 microg ml(-1) using this method, I was
      determined in the presence of up to 90% of II. The proposed method was applied
      for the analysis of I in tablet form as well as in human plasma. The last method
      depends on using TLC separation of I from its oxidative degradate II and I was
      then determined spectrodensitometrically. The mobile phase was methanol :
      chloroform : 25% ammonia (16 : 64 : 0.1 by volume). The linearity range was found
      to be 2-15 microg/spot. This method was applied to the analysis of I in both
      powder and tablet form using acetonitrile as a solvent.

PMID- 17015990
TI  - New acetylenic glucosides from Carthamus tinctorius.
AB  - Two new acetylenic glucosides, 4',6'-acetonide-8Z-decaene-4,6-diyne-1-O-beta-D
      glucopyranoside named carthamoside A(1) (1) and 4,6-decadiyne-1-O-beta-D
      glucopyranoside named carthamoside A(2) (2), along with one known acetylenic
      glucoside, 8Z-decaene-4,6-diyne-1-O-beta-D-glucopyranoside (3), have been
      isolated from the air-dried flower of Carthamus tinctorius, these structures have
      been identified on the basis of spectroscopic methods.

PMID- 17015989
TI  - Steroidal glycosides and aromatic compounds from Smilax riparia.
AB  - Two new steroidal glycosides named riparosides A (1) and B (2), and two aromatic
      compounds (3, 4), together with four known flavonoid derivatives have been
      isolated from the EtOH extract of the rhizomes and roots of Smilax riparia A. DC.
      The structure of riparoside A (1) was determined to be 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl
      3beta,20alpha-dihydroxy-5alpha-furost-22(23)-ene 26-O-beta-D-glucopyranoside.
      Riparoside B (2) was characterized as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha
      L-rhamnopyranosyl-(1-->6)]-beta-D-glucopyranosyl 3beta,16beta-dihydroxy-5alpha
      pregnan-20-one 16-O-[5-O-beta-D-glucopyranosyl 5-hydroxy-4-methyl-pentanoic acid]
      ester 26-O-beta-D-glucopyranoside. Compounds 3 and 4 were elucidated as a
      sucrosyl ferulic acid ester and 7-O-methyl-10-oxythymol gentiobioside,
      respectively.

PMID- 17015991
TI  - Facile aerobic photo-oxidation of aldehydes in the presence of catalytic lithium
      bromide.
AB  - Aldehydes were found to be oxidized to the corresponding carboxylic acid in the
      presence of catalytic lithium bromide under photo-irradiation.

PMID- 17015992
TI  - New approach to the total synthesis of (-)-zeylenone from shikimic acid.
AB  - The natural antitumor product (-)-zeylenone was prepared for the first time in a
      stereoselective synthesis from shikimic acid.

PMID- 17015993
TI  - 2,3'-Dihydroxycanthaxanthin, a new carotenoid with a 2-hydroxy-4-oxo-beta-end
      group from the hermit crab, Paralithodes brevipes.
AB  - A new carotenoid with a 2-hydroxy-4-oxo-beta-end group was isolated from the
      hermit crab, Paralithodes brevipes, as a minor component. Its structure was
      determined to be 2,3'-dihydroxy-beta,beta-carotene-4,4'-dione (1) by spectral
      data and the compound was named 2,3'-dihydroxycanthaxanthin. Chiral resolution of
      1 by HPLC using a chiral column provided two stereoisomers, 1a and 1b. The 3'R
      and 3'S chirality were determined for 1a and 1b, respectively, by CD spectra.

PMID- 17015995
TI  - Verification of cefmetazole and cefpodoxime proxetil contamination to other
      pharmaceuticals by liquid chromatography-tandem mass spectrometry.
AB  - Cross-contamination is a critical issue for pharmaceutical manufacturing,
      especially for beta-lactam antibiotics. Thus, an analytical method for the
      simultaneous determination of beta-lactam antibiotics cefmetazole (CMZ) and
      cefpodoxime proxetil (CPDXPR) contaminants in non-beta-lactam pharmaceuticals was
      developed using high-performance liquid chromatography-tandem mass spectrometry.
      The developed method was found to be sensitive at the detection limit of 0.002
      ppm for both compounds. Mean recoveries of CMZ and CPDXPR from olmesartan
      medoxomil (OLM) tablets were 96.7 to 102.2% and 88.9 to 94.2%, respectively. The
      developed method was successfully applied for the verification of CMZ and CPDXPR
      contamination to actually manufactured OLM tablets.

PMID- 17015994
TI  - Studies on the constituents of the leaves of Baccharis dracunculifolia
      (Asteraceae) and their cytotoxic activity.
AB  - A new sesquiterpene, named baccharisketone (1), and a new monoterpene, p
      methoxythymol acetate (2), were isolated from the leaves of Baccharis
      dracunculifolia along with seventeen known compounds (3-19). The structures of
      the new compounds were determined by spectroscopic means. The growth inhibitory
      activity of the isolated compounds against leukemia cells (L 1210) was tested and
      three terpene phenols (4, 6, 17) and five sesquiterpene alcohols (8, 10, 11, 13,
      16) were found to exhibit strong cytotoxic activity.

PMID- 17015996
TI  - C-24 stereochemistry of marine sterols: (22E)-24-(isopropenyl)-22
      dehydrocholesterol and 24-isopropenylcholesterol.
AB  - The C-24 configuration of (22E,24xi)-24-isopropenyl-22-dehydrocholesterol (1),
      which was recently isolated from the Colombian Caribbean sponge, Topsentia
      ophiraphidites, was investigated. Synthesis of the stereodefined (24R)- and (24S)
      (22E)-24-isopropenyl-22-dehydrocholesterols (1a, 1b) followed by (1)H- and (13)C
      NMR data comparison of these sterols established the (24R)-configuration of 1. In
      addition, (24R)- and (24S)-24-isopropenylcholesterols (2a and 2b) were also
      synthesized and their NMR data are provided. The C-24 configurations of the
      samples of 24-isopropenylcholesterol reported previously are discussed.

PMID- 17015997
TI  - Pulmonary infections in patients with rheumatoid arthritis who have received anti
      TNF therapy.

PMID- 17015998
TI  - Abducens nerve palsy and ipsilateral incomplete Horner syndrome: a significant
      sign of locating the lesion in the posterior cavernous sinus.

PMID- 17015999
TI  - Clinical comparative study of sulbactam/ampicillin and imipenem/cilastatin in
      elderly patients with community-acquired pneumonia.
AB  - OBJECTIVE: To evaluate the clinical usefulness of sulbactam/ampicillin therapy
      for community-acquired pneumonia in the elderly. METHODOLOGY: A randomized
      prospective clinical study was conducted in the elderly patients with moderate-to
      severe community-acquired bacterial pneumonia. RESULTS: Overall clinical efficacy
      of sulbactam/ampicillin therapy (6 g/day) in these patients (efficacy rate:
      91.4%) was comparable to that of imipenem/cilastatin therapy (1 g/day; efficacy
      rate: 87.5%), when each therapy was administered intravenously twice daily for 7
      14 days. With regard to clinical efficacy based on disease severity,
      bacteriological efficacy, improvement of chest X-ray findings and adverse
      reactions, the two therapies were comparable. CONCLUSION: These results suggest
      that sulbactam/ampicillin therapy has excellent efficacy and tolerability and
      that it may be highly effective, even in severe cases of pneumonia. This regimen
      may thus serve as first-line treatment for the treatment of community-acquired
      pneumonia in elderly patients.

PMID- 17016000
TI  - Benign symmetric lipomatosis associated with alcoholism.
AB  - A 46-year-old man was diagnosed as having benign symmetric lipomatosis (BSL)
      based on the grotesque physical examination findings and subcutaneous fat tissue
      biopsy. Although markedly overweight, the glucose tolerance was normal and
      insulin levels indicated no remarkable insulin resistance on the 75 g oral
      glucose tolerance test. Furthermore his visceral fat tissue was very slight and
      the circulating adiponectin concentration was high those which suggesting a high
      insulin sensitivity. In addition, the relevance of alcohol in the onset of BSL is
      strongly suggested based on alcoholic hepatopathy and the history of the
      development of grotesque physical appearance associated with increased alcohol
      consumption.

PMID- 17016001
TI  - Acute pneumonia and empyema caused by Mycobacterium intracellulare.
AB  - Nontuberculous mycobacterial infection is rarely accompanied by pleural
      involvement. We report a very rare case of M. intracellulare pulmonary disease
      with pleural empyema. A 56-year-old man was admitted to our hospital because of
      fever, purulent sputum and pleuritic chest pain. A chest radiograph and CT
      revealed pneumonic consolidation in the left lower lobe and loculated
      hydropneumothorax. The sputum smear was positive for acid fast bacilli. The
      aspirated pleural fluid was grossly purulent and the smear of the pleural
      effusion was also positive for acid fast bacilli. M. intracellulare was
      identified by culture and PCR from sputum and pleural fluid specimens. The
      patient improved with percutaneous tube drainage of the purulent effusion and
      antibiotic treatment including clarithromycin, rifampicin, ethambutol and
      streptomycin.

PMID- 17016002
TI  - Acute eosinophilic pneumonia caused by calcium stearate, an additive agent for an
      oral antihistaminic medication.
AB  - A 70-year-old man was admitted to our hospital because of dyspnea after taking an
      antihistaminic agent (homochlorcyclizine hydrochloride) for itching. Chest
      roentgenogram showed infiltration in the left lung field, and laboratory data
      revealed eosinophilia. Examination of the bronchoalveolar lavage fluid revealed
      an increased eosinophil count. A drug lymphocyte stimulation test was positive
      only for calcium stearate, an additive contained in the homochlorcyclizine
      hydrochloride tablet. The pulmonary infiltration and clinical symptoms subsided
      after withdrawal of all drugs and initiation of glucocorticoid therapy.
      Therefore, we concluded that this patient's pulmonary disease was caused by
      calcium stearate, an additive for an antihistaminic drug. An allergic reaction to
      a drug's additive material should be considered as a rare cause of drug-induced
      acute eosinophilic pneumonia.

PMID- 17016003
TI  - Prevalence rates of antiphospholipid antibodies in ischemic stroke patients.

PMID- 17016004
TI  - Fungal effusions associated with invasive pulmonary aspergillosis.

PMID- 17016005
TI  - Laryngo-tracheo-bronchial amyloidosis presenting severe airway stenosis.

PMID- 17016006
TI  - A splenic hydatid cyst case presented with lumbar pain.
AB  - A splenic hydatid cyst is a rare clinical entity from among abdominal hydatid
      cysts, even in endemic countries. Here, a case with lumbar pain due to a giant
      splenic hydatid cyst is presented. The importance of this case is that the
      patient presented at the clinic with only lumbar pain. Initial direct abdominal
      plain radiography showed a giant abdominal calcification in the spleen and
      further examinations revealed involvement of three organs: spleen, lung, and
      liver.

PMID- 17016007
TI  - Contribution of physical fitness component to health status in middle-aged and
      elderly males.
AB  - This study determined the physical fitness component that contributes to
      improving and maintaining health status for each age group as well as quantifying
      the degree of the relationship between health status and physical fitness in
      middle-aged and elderly males. The participants were 995 males aged 30 to 69
      years. Ten physical fitness tests and medical checkups were performed. The
      participants were divided into a healthy group and an unhealthy group according
      to health status. Multiple discriminant analysis was applied to the multivariate
      data. Correct discriminant probabilities of the multiple discriminant function to
      discriminate the healthy and unhealthy groups for males ranged from 67.0% to
      75.1%. These findings suggest that there is a relatively high relationship
      between the health status and physical fitness level for middle-aged and elderly
      males. With each individual's discriminant score calculated using the multiple
      discriminant function as the index of the degree of health, the Pearson's
      correlation coefficient of the discriminant score and the performance in each
      physical fitness test were calculated. The age change between 30 and 69 years old
      was classified into five patterns according to the contribution. The result of
      this study is considered to be useful as objective data to prepare an exercise
      program considering the contribution of the physical fitness component of health
      status.

PMID- 17016008
TI  - The influence of gender, athletic events, and athletic experience on the
      subjective dominant hand and the determination of the dominant hand based on the
      laterality quotient (LQ) and the validity of the LQ.
AB  - This study aimed to reveal the influence of gender, athletic events and athletic
      experience on the subjective dominant hand and the dominant hand based on the
      laterality quotient (LQ). It also aimed to examine the validity of the Edinburgh
      Inventory (Oldfield, 1971). Males and females (n=3,726) living in 7 prefectures
      in Japan (age: 16-45 yrs) participated in this survey. Analysis was performed on
      3,557 separate datasets with high reliability. The reliability of the survey was
      examined using a test-retest method consisting of 100 people selected randomly
      from all participants. All participants provided the same answers for each
      question. The influence of gender, event and experience was examined for the
      subjective and LQ-based dominant hands. In addition, concordance rates of the
      subjective dominant hand and the LQ-based dominant hand and both dominant hands
      were examined. Differences of concordance rates between hands used in the 10
      movement questions of the Inventory and the subjective dominant hand were tested
      using the chi(2) test. The frequency differences among items were tested using
      Ryan's method (multiple comparisons). Significant gender differences were found
      between rates of the LQ-based dominant hand (males: 94.4%; females: 96.6%) and
      the subjective dominant hand (males: 91.6%; females: 94.0%), but the degree was
      only 2.0-4.0%. Insignificant differences were found among athletic events, two
      groups of different athletic experience, and gender according to each athletic
      event. The subjective dominant hand almost always agreed with the LQ-based
      dominant hand (complete concordance rate=0.96, kappa=0.67). Of the 10 question
      items, inexperienced answers were found only in the item "Knife (without fork)".
      The "Toothbrush", "Broom (upper hand)", and "Opening box (lid)" items had
      significantly lower correspondence with the subjective dominant hand (79.7-87.0%)
      than the other items (92.1-95.7%). In conclusion, athletic experience appears to
      have little influence on handedness, although there is a slight gender
      difference. The subjective dominant hand almost always agrees with the dominant
      hand based on the Inventory. A more efficient handedness inventory may be
      constructed by excluding the above 4 items.

PMID- 17016009
TI  - Thermal insulation and body temperature wearing a thermal swimsuit during water
      immersion.
AB  - This study evaluated the effects of a thermal swimsuit on body temperatures,
      thermoregulatory responses and thermal insulation during 60 min water immersion
      at rest. Ten healthy male subjects wearing either thermal swimsuits or normal
      swimsuits were immersed in water (26 degrees C or 29 degrees C). Esophageal
      temperature, skin temperatures and oxygen consumption were measured during the
      experiments. Metabolic heat production was calculated from oxygen consumption.
      Heat loss from skin to the water was calculated from the metabolic heat
      production and the change in mean body temperature during water immersion. Total
      insulation and tissue insulation were estimated by dividing the temperature
      difference between the esophagus and the water or the esophagus and the skin with
      heat loss from the skin. Esophageal temperature with a thermal swimsuit was
      higher than that with a normal swimsuit at the end of immersion in both water
      temperature conditions (p<0.05). Oxygen consumption, metabolic heat production
      and heat loss from the skin were less with the thermal swimsuit than with a
      normal swimsuit in both water temperatures (p<0.05). Total insulation with the
      thermal swimsuit was higher than that with a normal swimsuit due to insulation of
      the suit at both water temperatures (p<0.05). Tissue insulation was similar in
      all four conditions, but significantly higher with the thermal swimsuit in both
      water temperature conditions (p<0.05), perhaps due to of the attenuation of
      shivering during immersion with a thermal swimsuit. A thermal swimsuit can
      increase total insulation and reduce heat loss from the skin. Therefore, subjects
      with thermal swimsuits can maintain higher body temperatures than with a normal
      swimsuit and reduce shivering thermo-genesis.

PMID- 17016010
TI  - Time under tension and blood lactate response during four different resistance
      training methods.
AB  - Mechanical stimuli have often been suggested to be the major determinant of
      resistance training adaptations; however, some studies suggested that metabolic
      changes also play an important role in the gains of muscle size and strength.
      Several resistance training methods (RTM) have been employed with the purpose of
      manipulating mechanical and metabolic stimuli; however, information about their
      physiological effects are scarce. The objective of this study was to compare the
      time under tension (TUT) and blood lactate responses among four different RTM
      reported in the literature. The four RTM were performed in a knee extension
      machine at 10 repetition maximum (RM) load by 12 recreationally trained young
      men. The RTM tested were: 10RM, super-slow (SL-subjects performed one 60-second
      repetition with 30 seconds for eccentric and 30 seconds for concentric phase),
      functional isometrics (FI-in each repetition, a five-second maximal isometric
      contraction was executed with the knees fully extended) and adapted vascular
      occlusion (VO-subjects performed a 20-second maximal isometric contraction with
      the knees fully extended and immediately proceeded to normal isoinertial lifts).
      According to the results, all RTM produced significant increases in blood lactate
      levels. However, blood lactate responses during FI (4.48+/-1.57 mM) and VO
      (4.23+/-1.66 mM) methods were higher than the SL method (3.41+/-1.14 mM). The TUT
      for SL (60 s), FI (56.33+/-6.46 s), and VO (53.08+/-4.76 s) methods were higher
      than TUT for 10RM (42.08+/-3.18 s). Additionally, TUT for the SL method was
      higher than TUT during the VO method. Therefore, the SL method may not be
      recommended if one wants to provide a high metabolic stimulus. The FI method
      appeared to be especially effective in promoting both type of stimuli.

PMID- 17016011
TI  - Optimal vibration stimulation to the neck extensor muscles using hydraulic
      vibrators to shorten saccadic reaction time.
AB  - Optimal vibration stimulation to the neck extensor muscles using hydraulic
      vibrators to shorten the saccadic reaction time was examined. Subjects were 14
      healthy young adults. Visual targets (LEDs) were located 10 degrees left and
      right of a central point. The targets were alternately lit for random durations
      of 2-4 seconds in a resting neck condition and various vibration conditions, and
      saccadic reaction times were measured. Vibration amplitude was 0.5 mm in every
      condition. The upper trapezius muscles were vibrated at 40, 60, 80, and 100 Hz in
      a sub-maximum stretch condition in which the muscles were stretched at 70% of
      maximum stretch. In addition, the muscles were vibrated at 60 Hz with the muscles
      maximally stretched, with 70% vertical pressure without stretching, and with
      vibration applied to the skin in the same area as the muscle vibration. At 60,
      80, and 100 Hz at 70% maximum stretch, saccadic reaction time shortened
      significantly compared with the resting neck condition. However, no significant
      difference in the reaction time was observed among the frequencies. The saccadic
      reaction times in the maximum stretch condition, muscle pressure condition, and
      skin contact condition did not differ significantly from that in the resting neck
      condition. Vibration stimulation to the trapezius with 60-100 Hz frequencies at
      0.5 mm amplitude in the sub-maximum stretch condition was effective for
      shortening saccadic reaction time. The main mechanism appears to be Ia
      information originating from the muscle spindle.

PMID- 17016013
TI  - [Biological responses to low dose radiation--hormesis and adaptive responses].
AB  - "Hormesis" is defined, originally in the field of toxicology, as a phenomenon in
      which a harmful substance gives stimulating effects to living organisms when the
      quantity is small. The concept was extended and applied to ionizing radiation,
      high doses of which are harmful. Although radiation has been thought to be, based
      on findings in high dose ranges, harmful no matter low the dose is, recent
      investigation revealed that living organisms possess the ability to respond to
      low-dose radiation in very sophisticated ways. A good example of such responses
      is the so-called radiation adaptive response, a process in which acquired
      radioresistance is induced by low-dose radiation given in advance. The
      stimulation of certain bioprotective functions, including antioxidative capacity,
      DNA repair functions, apoptosis, and immune functions are thought to underly the
      adaptive response. The adaptive response is effective for chromosome induction,
      acute death, and tumorigenesis induced by high doses of radiation. Radiation
      hormesis and adaptive response provide a new scope in the risk assessment and
      medical application of ionizing radiation.

PMID- 17016014
TI  - [Induction of radio-resistance by low dose X-irradiation].
AB  - A priming X-ray exposure to 0.05-0.10 Gy or 0.3-0.5 Gy imparts radioresistance
      (decrease in bone marrow death rate after high-dose X-rays) in mice 2-2.5 months
      or 9-17 days postexposure, respectively. This radiation-adaptive response in
      whole animals differs from that in cells observed several hours to several days
      (at most) later. An adaptive response was observed in ICR and C57BL/6 strains of
      mice, but not in BALB/c and C3H strains. The biological mechanisms of an acquired
      radioresistance induced by a priming exposure to 0.45 Gy in C57BL/6 mice have
      been studied. The recovery of blood-forming stem cells, determined as endogenous
      spleen colonies, was markedly stimulated by priming irradiation. The reduction in
      bone marrow death seems chiefly due to the stimulated recovery of blood-forming
      stem cells. But mice pretreated at this priming dose did not show a marked
      recovery of peripheral blood cell counts after challenging irradiation with mid-
      or sublethal X-ray doses (a significant, albeit slight, increase in the blood
      cell counts in the preirradiated group was observed after a lower challenging
      exposure to 5.0 Gy). The adaptive response depends on p53, as observed in cell
      experiments. The stem cells might produce an unknown factor(s) that contributes
      to acquired radioresistance. In a preliminary experiment, the life span of
      C57BL/6 mice after ascertaining their 30-day survival rates was not shortened by
      preirradiation.

PMID- 17016015
TI  - [Antitumor effects by low dose total body irradiation].
AB  - Total-body irradiation (TBI) with 0.02-0.25 Gy has been reported to have
      antitumor effects. In mice, low-dose TBI induces tumor growth delay,
      antimetastatic effects, suppressive effects on the incidence of spontaneous
      thymiclymphoma, sensitization of tumor to ionizing radiation, and decrease in
      TD50 value. In artificial metastasis, 0.20 Gy TBI suppressed lung metastasis when
      it was conducted between 3 h before and 3 h after tumor cell injection into a
      tail vein. In spontaneous metastasis, 0.15-0.20 Gy TBI suppressed lung
      metastasis. Irradiation with 0.15 Gy twice a week from 11 weeks of age for 40
      weeks significantly suppressed the incidence of spontaneous thymic lymphoma in
      AKR/J mice, which caused prolonged life span. Low-dose TBI has been used in the
      clinical treatment of lymphomatous malignancies including chronic lymphocytic
      leukaemia (CLL) and non-Hodgkin's lymphoma (NHL). The usual practice was to give
      0.1 Gy TBI three times a week or 0.15 Gy TBI two times a week to a total dose of
      1.5 Gy. Despite this low total dose, low-dose fractionated TBI could induce long
      term remissions and was as effective as the chemotherapy to which it was
      compared. Experimental data suggest that the antitumor effects of low-dose TBI
      could be explained by immune enhancement, induction of apoptosis, and intrinsic
      hypersensitivity to low-dose irradiation. Possible mechanisms of immune
      enhancement are elimination of the T-suppressor subset of lymphocytes and
      augmentation of the immune response including alteration of cytokine release and
      enhanced proliferative activity of lymphocytes to mitogenic stimuli.

PMID- 17016016
TI  - [Induction of glutathione and activation of immune functions by low-dose, whole
      body irradiation with gamma-rays].
AB  - We first examined the relation between the induction of glutathione and immune
      functions in mice after low-dose gamma-ray irradiation. Thereafter, inhibition of
      tumor growth by radiation was confirmed in Ehrlich solid tumor (EST)-bearing
      mice. The total glutathione level of the splenocytes transiently increased soon
      after irradiation and reached a maximum at around 4 h postirradiation.
      Thereafter, the level reverted to the 0 h value by 24 h postirradiation. A
      significantly high splenocyte proliferative response was also recognized 4 h
      postirradiation. Natural killer (NK) activity was also increased significantly in
      a similar manner. The time at which the response reached the maximum coincided
      well with that of maximum total glutathione levels of the splenocytes in the
      gamma-ray-irradiated mice. Reduced glutathione exogenously added to splenocytes
      obtained from normal mice enhanced the proliferative response and NK activity in
      a dose-dependent manner. The inhibitory effects of radiation on tumor growth was
      then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four
      times, before and within an early time after inoculation) significantly delayed
      the tumor growth. Finally, the effect of single low-dose (0.5 Gy), whole-body
      gamma-ray irradiation on immune balance was examined to elucidate the mechanism
      underlying the antitumor immunity. The percentage of B cells in blood lymphocytes
      was selectively decreased after radiation, concomitant with an increase in that
      of the helper T cell population. The IFN-gamma level in splenocyte culture
      prepared from EST-bearing mice was significantly increased 48 h after radiation,
      although the level of IL-4 was unchanged. IL-12 secretion from macrophages was
      also enhanced by radiation. These results suggest that low-dose gamma-rays induce
      Th1 polarization and enhance the activities of tumoricidal effector cells,
      leading to an inhibition of tumor growth.

PMID- 17016017
TI  - [Low-dose radiation effects and intracellular signaling pathways].
AB  - Accumulated evidence has shown that exposure to low-dose radiation, especially
      doses less than 0.1 Gy, induces observable effects on mammalian cells. However,
      the underlying molecular mechanisms have not yet been clarified. Recently, it has
      been shown that low-dose radiation stimulates growth factor receptor, which
      results in a sequential activation of the mitogen-activated protein kinase
      pathway. In addition to the activation of the membrane-bound pathways, it is
      becoming evident that nuclear pathways are also activated by low-dose radiation.
      Ionizing radiation has detrimental effects on chromatin structure, since
      radiation-induced DNA double-strand breaks result in discontinuity of
      nucleosomes. Recently, it has been shown that ATM protein, the product of the ATM
      gene mutated in ataxia-telangiectasia, recognizes alteration in the chromatin
      structure, and it is activated through intermolecular autophosphorylation at
      serine 1981. Using antibodies against phosphorylated ATM, we found that the
      activated and phosphorylated ATM protein is detected as discrete foci in the
      nucleus between doses of 10 mGy and 1 Gy. Interestingly, the size of the foci
      induced by low-dose radiation was equivalent to the foci induced by high-dose
      radiation. These results indicate that the initial signal is amplified through
      foci growth, and cells evolve a system by which they can respond to a small
      number of DNA double-strand breaks. From these results, it can be concluded that
      low-dose radiation is sensed both in the membrane and in the nucleus, and
      activation of multiple signal transduction pathways could be involved in
      manifestations of low-dose effects.

PMID- 17016018
TI  - [Steroid (glucocorticoid)-induced cataract].
AB  - Glucocorticoids (GC) have been widely used as a therapeutic drug for various
      diseases. However, there are many complications of GC therapy including
      cataracts. In a series of studies to elucidate the actions of GC using 15-day-old
      developing chick embryos, we found that GC produced hyperglycemia, hyperlipemia,
      osteoporosis, and cataractous lenses with a high incidence (>90%) within 48 h.
      Cataract formation is caused by oxidative stresses, probably derived from GC
      effects on the main target organ, the liver, and can be prevented by radical
      scavengers including ascorbic acid, and insulin. Ascorbic acid does not inhibit
      the inflammatory and immunosuppressive effects of GC. Therefore by analyzing and
      decreasing risk factors producing side effects, it will be possible to improve GC
      therapy without the loss of GC activity.

PMID- 17016020
TI  - [Development and biological applications of various bioimaging probes].
AB  - Fluorescence imaging is the most powerful technique currently available for
      continuous observation of dynamic intracellular processes in living cells.
      However, only a very limited range of biomolecules can be visualized because of
      the lack of flexible design strategies for fluorescence probes. In our
      laboratory, it was elucidated that fluorescein which has been widely employed as
      a core of fluorescence probes could be understood as a directly linked electron
      donor/fluorophore acceptor system. Fluorescence properties of fluorescein
      derivatives could be easily anticipated and modulated by controlling the rate of
      photoinduced electron transfer (PeT) from the donor moiety to the xanthene
      fluorophore. Further, we found that the opposite direction of PeT from the
      singlet excited fluorophore to the electron acceptor moiety could be occurred.
      More than twenty probes for imaging of nitric oxide, beta-galactosidase, highly
      reactive oxygen species, zinc ion et al. have been developed according to precise
      and rational design strategies based on PeT mechanism.

PMID- 17016019
TI  - [Learning toxicology from carbon tetrachloride-induced hepatotoxicity].
AB  - The mechanism of carbon tetrachloride (CCl4)-induced hepatotoxicity, especially
      necrosis and fatty liver, has long been a challenging subject of many researchers
      from various fields over the past 50 years. Even though the mechanisms of tissue
      damages are different among chemicals and affected tissues, CCl4 has played a
      role as a key substance of tissue injury. A number of studies have been conducted
      and various hypotheses have been raised. As a result, several important basic
      mechanisms of tissue damages have emerged, involving metabolic activation,
      reactive free radical metabolites, lipid peroxidation, covalent binding and
      disturbance of calcium homeostasis. Recent studies also revealed inflammation and
      regeneration as important modification factors in the tissue injury. The author
      attempted to summarize the history of CCl4 research with some emphasis on the
      experiments done by the author and his colleagues. Their studies with isolated
      perfused rat liver suggest that covalent binding of CCl4 metabolites rather than
      lipid peroxidation has a significant role in the production of centrilobular
      necrosis following CCl4 administration. Further studies are necessary to unveil
      detailed mechanisms of hepatocyte necrosis induced by CCl4.

PMID- 17016021
TI  - [Structural and functional characterization of biological macromolecules by mass
      spectrometry].
AB  - Mass spectrometry has widely been used as a tool for identification of proteins
      in the research fields of biochemistry and clinical chemistry because it can
      provide accurate information on molecular masses of biological molecules with a
      small amount of sample in a short time. If mass spectrometry is properly used, it
      can also give information on the tertiary structure or on the molecular
      interactions of biological macromolecules. The present paper focuses on the role
      of mass spectrometry as a tool for the investigation on the tertiary structure of
      proteins and on the biological molecular interactions that play essential roles
      in various biological events.

PMID- 17016022
TI  - [Design and synthesis of non-proteinogenic amino acids and secondary structures
      of their peptides].
AB  - Replacement of the alpha-hydrogen atom of L-alpha-amino acids with an alkyl
      substituent results in alpha,alpha-disubstituted amino acids. The modification
      changes the properties of the amino acids. Incorporation of alpha,alpha
      disubstituted amino acids into oligopeptides restricts the conformational freedom
      of their peptides. The author developed a synthetic route for optically active
      alpha-ethylated alpha,alpha-disubstituted amino acids using chiral cyclic 1,2
      diol, and disclosed that the preferred conformation of peptides composed of
      chiral alpha-ethylated disubstituted amino acids is a fully planar conformation,
      whereas that of chiral alpha-methylated disubstituted amino acids is a 3(10)
      helical structure. Furthermore, the author designed and synthesized two chiral
      cyclic alpha,alpha-disubstituted amino acids, i.e., (3S,4S)-1-amino-3,4
      di(methoxy)cyclopentanecarboxylic acid {(S,S)-Ac5cdOM}, and (1R,6R)-8
      aminobicyclo-[4.3.0]non-3-ene-8-carboxylic acid {(R,R)-Ab5,6=c}. They do not have
      a chiral center at the alpha-position, but do have chiral centers on the side
      chain cyclopentane or the bicyclic skeleton. The preferred secondary structure of
      the (S,S)-Ac5cdOM homopeptides was the left-handed (M) 3(10)-helical structure
      (hexapeptide) and the left-handed (M) alpha-helical structure (octa- and
      decapeptides), while that of the (R,R)-Ab5,6=c hexapeptide was both the right
      handed (P) and left-handed (M) 3(10)-helices. These results indicate that the
      side-chain chiral centers affect the secondary structure of their peptides, and
      the side-chain chiral environment is important for the control of the helical
      screw direction of peptides.

PMID- 17016023
TI  - [Molecular pharmacological studies on potassium channels and their regulatory
      molecules].
AB  - K+ channels play important roles in the control of a large variety of
      physiological functions such as muscle contraction, neurotransmitter release,
      hormone secretion, and cell proliferation. Over 100 cloned K+ channel pore
      forming alpha and accessory beta subunits have been identified so far. Here, we
      introduce a series of molecular pharmacological and physiological studies on some
      types of voltage-dependent K+ channels and Ca2+-activated K+ channels. We
      examined molecular cloning and functional characterization of novel, fast
      inactivating, A-type K+ channel alpha (Kv4.3L) and beta (KChIP2S) subunits
      predominantly expressed in mammalian heart and found the sites in Kv4 channels
      for 1) the regulation of voltage dependency and 2) the CaMKII phosphorylation in
      the C-terminal cytoplasmic domain. Moreover, we found that delayed rectifier-type
      K+ channels (ERG1 and KCNQ) contribute to the resting membrane conductance in
      vascular and gastrointestinal smooth muscles. The large-conductance Ca2+
      activated K+ (BK) channel is ubiquitously expressed and contributes to diverse
      physiological processes. Recent reports have shown that a BK-like channel
      (mitoKCa) is expressed in cardiac mitochondria, suggesting that BK channel
      openers protect mammalian hearts against ischemic injury. Our studies revealed
      that BKbeta1 interacts with cytochrome c oxidase I (Cco1) in cardiac
      mitochondria, and that the activation of BK channels by 17beta-estradiol results
      in a significant increase in the survival rate of ventricular myocytes. These
      findings suggest that BKbeta1 may play an important role in the regulation of
      cell respiration in cardiac myocytes and be a target for the modulation by female
      gonadal hormones.

PMID- 17016025
TI  - Structural features of pharmacy function--the analysis using structural equation
      modeling.
AB  - In order to examine the structural features of community pharmacy function and to
      clarify areas meriting priority in efforts to expand pharmacy functions in the
      home care field, a questionnaire survey was conducted. Using the distribution of
      responses regarding the actual conditions entailed in the 16 categories of
      pharmacy services, factor analysis was carried out. Structural equation modeling
      was performed and the fitness of the path model constructed to study the
      interrelatedness of the individual factors extracted by factor analysis was
      considered. Four factors comprised pharmacy services "dispensing", "supply of
      goods", "offering home care", and "cooperation in community health and medical
      programs". The interrelatedness of four pharmacy functions by the result of
      structural equation modeling indicated the following insights. 1) By
      strengthening "cooperation in community health and medical programs", it is
      possible to directly improve the functions of "dispensing", and "offering home
      care". An improvement in "collecting and utilizing patient information",
      "providing appropriate instruction", "providing introductions to medical
      institutions and physicians", and "supplying over-the-counter drugs" can be
      expected as a result of direct benefits accrued by "cooperation in community
      health and medical programs". 2) By strengthening "offering home care", it is
      possible to directly improve "supply of goods". An improvement in "stocking long
      term care goods and sanitary goods" can be expected as a result of direct
      benefits accrued by "offering home care". In conclusion, this study indicated
      that the areas meriting priority in the expansion and upgrading of pharmacy
      functions is stronger "cooperation in community health and medical programs".

PMID- 17016024
TI  - [Biological activity of Asp-hemolysin as a regulation factor to atherogenic
      effect by oxidized low-density lipoprotein].
AB  - Oxidatively modified low-density lipoprotein (OxLDL) is present in
      atherosclerotic lesions and has been proposed to play an important role in
      atherogenesis. Asp-hemolysin, a hemolytic toxin from Aspergillus fumigatus, is a
      binding protein for OxLDL. This study was undertaken to clarify the biological
      activity of OxLDL and the potentially of Asp-hemolysin as a regulation factor to
      atherogenic effect by OxLDL. We first analyzed the interaction between OxLDL and
      blood coagulation factors, which are involved in the blood coagulation pathway.
      OxLDL caused prolongation of activated partial thromboplastin time (APTT) as a
      parameter of the intrinsic pathway of blood coagulation in a dose- and oxidation
      time-dependent manner. In addition, OxLDL significantly inhibited blood
      coagulation factor VIII, IX, and XI activity. Furthermore, we demonstrated that
      factor VIII binds to OxLDL. These results indicate that the binding of factor
      VIII to OxLDL affects the intrinsic pathway of the blood coagulation cascade.
      Next, to clarify the structure-function relationship of Asp-hemolysin, we
      expressed Asp-hemolysin in Escherichia coli as a fusion protein with a maltose
      binding protein (MBP) and purified it by affinity chromatography. The purified
      recombinant Asp-hemolysin showed an immunoreactivity with the anti-Asp-hemolysin
      antibody. In addition, MBP-Asp-hemolysin fusion protein exhibited binding
      activity to Ox-LDL as did native Asp-hemolysin. Furthermore, to investigate the
      effect of the Asp-hemolysin-related peptide (P-21), a synthetic peptide derived
      from a region of Asp-hemolysin that is rich in positive charges, on macrophage
      proliferation induced by OxLDL. P-21 inhibited OxLDL-induced macrophage
      proliferation in a dose-dependent manner. In addition, the binding analysis of P
      21 to OxLDL indicated that P-21 binds to OxLDL. These results indicate that P-21
      inhibits the OxLDL-induced macrophage proliferation through binding of P-21 to
      OxLDL. In conclusion, we have shown that OxLDL affects the intrinsic pathway of
      blood coagulation, and its mechanism is dependent on the binding of factor VIII
      to OxLDL. Furthermore, we indicate the possibility that Asp-hemolysin is a useful
      tool to investigate the pathophysiological significance of OxLDL. In particular,
      since the P-21, an Asp-hemolysin-related peptide, inhibits the OxLDL-induced
      macrophage proliferation through binding of P-21 to OxLDL, further study on the
      binding mechanism between Asp-hemolysin-related peptide and OxLDL may provide
      important information on the prevention and treatment of atherosclerosis.

PMID- 17016026
TI  - [Effects of long term administration of Shakuyaku-kanzo-To and Shosaiko-To on
      serum potassium levels].
AB  - Typical adverse effects of Shakuyaku-kanzo-To (SKT), an herbal medicine
      containing licorice, is a licorice-induced pseudoaldosteronism with hypokalemia
      and hypertension. The risk factors for this side effect are still unclear. To
      identify the risk factors, we surveyed 37 cases of licorice-induced
      pseudoaldosteronism in the literature and serum potassium levels in our patients
      receiving SKT and Shosaiko-To (SST), which contain 6 g and 1.5 g of licorice in
      the daily dose, respectively. In the case report survey, pseudoaldosteronism
      developed a median 35 (range 2-231) days after the administration of SKT, which
      is shorter than after SST (450, range 150-2190 days) and other licorice products
      including glycyrrhizin (210, range 14-730 days). A significant correlation was
      observed between the glycyrrhizin contents in the licorice preparations and the
      dosing periods for developing pseudoaldosteronism (r=-0.700, p<0.01). A negative
      correlation was also observed between serum potassium level and dosing period for
      SKT, but not for SST. The difference in age (65.3+/-11.6 vs. 57.2+/-17.3 y) and
      dosing period (57.3+/-66.3 vs. 19.0+/-24.3 days) between the patients with and
      without hypokalemia after the administration of SKT was statistically significant
      (p<0.05). The occurrence rate of hypokalemia including pseudoaldosteronism was
      around 80% with SKT administration for more than 30 days for patients exceeding
      60 years old. It was suggested that patient age (>60 y) and dosing period of SKT
      (>30 days) might be risk factors for developing pseudoaldosteronism or
      hypokalemia as well as coadministration of drugs inducing hypokalemia.

PMID- 17016028
TI  - Simultaneous analysis of 10 pyrethroid pesticides in natural medicines by GC/MS
      with negative chemical ionization.
AB  - Many methods for the determination of pesticides residues in food have been
      reported. Although natural medicines should be confirmed as safe as food, only a
      few methods for the determination of pesticide residues in natural medicines have
      been reported. In this study, 10 pyrethroid pesticides were detected in natural
      medicines by GC/MS with negative chemical ionization (NCI). GC/MS with NCI can
      detect halogenated pesticides selectively, and thus is suitable for the detection
      of pyrethroid pesticides. This study indicates that GC/MS with NCI is useful for
      analyzing pyrethroid pesticides in natural medicines.

PMID- 17016027
TI  - Effect of delta-elemene on Hela cell lines by apoptosis induction.
AB  - This study was designed to investigate the apoptosis-inducing activity of delta
      elemene on Hela cells in vitro. MTT assay and Hoechst 33258/PI fluorescence
      microscopy were used for this investigation. Apoptosis was further confirmed and
      quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized
      phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry.
      Generation of reactive oxygen species (ROS) was detected using CM-H2DCFDA.
      Western blots analysis was performed using antibodies against the pro-caspase-3,
      or PRAP (Poly (ADP-ribose) polymerase). The results showed that delta-elemene
      exhibited a marked antiproliferative effect on Hela cells in dose- and time
      dependent manners, and had little inhibition to normal human liver cell line WRL
      68. It was demonstrated that delta-elemene was capable of inducing DNA
      fragmentation in a dose- and time-dependent manner. AnV positivity and the
      disturbance of the polarized mitochondrial transmembrane potential (Deltapsim)
      suggested that delta-elemene induced apoptotic death of Hela cells. Western blot
      analysis demonstrated that delta-elemene activated the caspase-signaling pathway,
      leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and
      the subsequent cleavage of the caspase substrate PARP. Further, it was noted that
      the apoptotic effect of delta-elemene could be attenuated by L-Glutathione (GSH)
      or z-DEVD-fmk. It suggested that the increase in ROS generation might be involved
      in the mechanism of delta-elemene induced cell apoptosis.

PMID- 17016029
TI  - [Growth-stimulating effect of kallikrein on rat neural stem cells].
AB  - Tissue kallikrein is expressed in many species and is widely distributed
      throughout the body, including the brain. In general, this protease is well known
      to release the vasoactive peptide, kinin, from kininogen. We report here that
      kallikrein has a prominent growth-stimulating effect on neural stem cells
      prepared from the brains of prenatal rats. This growth-stimulating effect was
      suppressed by antiserum against rat tissue kallikrein. Since bradykinin B2
      receptor antagonist, Hoe140, did not suppress the growth-stimulating effect,
      kallikrein-mediated kinin release does not appear to be involved in this effect.
      Thus, our data suggest a new physiological function of kallikrein, the growth of
      neural stem cells. Such involvement would suggest that kallikrein is not only
      potentially involved in an important function of brain development, but also
      available for studies on regenerative medicine for neurons.

PMID- 17016030
TI  - Introduction and evaluation of a newly established holiday work system in the
      pharmacy ward at Municipal Ikeda Hospital.
AB  - At the Municipal Ikeda Hospital, a system in which pharmacists stationed in one
      ward pharmacy dispense drugs to be administered by injection and injectable
      preparations delivered to patients' bedsides was introduced in April 2000. This
      system was aimed at minimizing risks related to injections. Initially, however,
      on holidays, nurses played the roles of pharmacists in terms of the injections,
      and there were concerns over a possible rise in the incidence of errors (adverse
      events/near-misses) related to injections on these days compared with weekdays.
      Later, when planning to introduce a new holiday work system in the ward pharmacy,
      we took into account such factors as the number of pharmacists needed on
      holidays, their duties on holidays and the influence on weekday pharmacy activity
      of compensatory days-off taken by such pharmacists. In May 2004, the new holiday
      work system was introduced in the ward pharmacy. Under the new system, 5
      pharmacists work at the ward pharmacy on holidays. After this system was put into
      operation, the number of injections dispensed at the ward pharmacy averaged 230
      per day, and 177 per holiday. To evaluate the validity of this system, we
      recently conducted a questionnaire survey of nurses at our hospital. The survey
      involved 139 nurses. Of these nurses, 69.1% responded that the number of
      incidents (adverse events/near-misses) related to dispensing injections on
      holidays had decreased. Furthermore, 65.4% of the nurses reported a decrease in
      incidents related to the delivery and administration of injectable preparations.
      More than half of the nurses answered that the new system had made it easier for
      them to collect information on medicines and helped them provide better nursing
      services. When the nurses were asked to make a general assessment of the new
      system, 90% rated the system as "good." The results of this survey indicate that
      keeping the ward pharmacy open on holidays contributes to the promotion of the
      proper use of medicines, reduction of risks related to injections and improvement
      in the quality of medical care.

PMID- 17016031
TI  - Neuropeptide glutamic acid-isoleucine may induce luteinizing hormone secretion
      via multiple pathways.
AB  - Neuropeptide glutamic acid-isoleucine (NEI) is a 14-amino acid peptide processed
      from prepro-melanin-concentrating hormone (ppMCH). In males, the localization of
      NEI is almost identical to that of MCH, the cell bodies of both being located
      primarily in the lateral hypothalamic area and zona incerta, projecting fibers
      throughout the brain. Although MCH has been widely studied, the role that NEI
      plays in brain circuitry has been poorly investigated. Recently, we showed that
      intracerebroventricular injection of NEI increases serum luteinizing hormone (LH)
      levels. In order to identify the anatomical substrate underlying this effect, we
      used combined immunohistochemistry methods to analyze the forebrains of females
      on the diestrus and proestrus days, as well as those of ovariectomized females
      treated with estradiol benzoate, with estradiol benzoate plus progesterone or
      with sesame oil (control animals). We found that ovariectomized females with no
      steroid treatment showed an increased number of NEI-immunoreactive neurons in the
      medial zona incerta. In addition, we observed dense to moderate NEI innervation
      of areas related to reproduction, including the organum vasculosum of the lamina
      terminalis, the anteroventral periventricular nucleus (AVPV) and the median
      eminence. The NEI fibers were in close apposition with the AVPV and gonadotropin
      releasing hormone (GnRH) neurons expressing Fos in the afternoon of the proestrus
      day or following administration of estradiol benzoate plus progesterone. In the
      median eminence, NEI varicosities and terminal-like structures were in close
      proximity to blood vessels and GnRH fibers. Our results suggest that NEI might
      induce LH secretion in one of the following ways: by direct release into the
      median eminence, by modulation of GnRH neurons located in the preoptic area, by
      modulation of the GnRH terminals located in the median eminence or by an additive
      effect involving other neurotransmitters or neurohormones. Release of NEI might
      also induce LH secretion indirectly by modulating AVPV neurons.

PMID- 17016032
TI  - Endocrine tumors of the ileum: factors correlated with survival.
AB  - AIM: To evaluate the most important factors correlated with survival in patients
      with endocrine tumors of the ileum, both at the time of diagnosis and during the
      follow-up period. METHODS: Fifty-nine patients with ileal endocrine tumors
      diagnosed in our institution between 1990 and 2004 were studied. RESULTS: The
      study included 36 men (61%) and 23 women (39%). The median age of the patients at
      the time of diagnosis was 61.4 (range 18-83) years. The median follow-up period
      was 71.9 (range 5-287) months. Forty patients (67.8%) were still alive at the end
      of the study; the median survival time was 172 months, and the 5-year survival
      rate was 78.9%. By univariate analysis, the survival rate was significantly
      related to female sex (p = 0.024) and flushing alone (p = 0.028) and associated
      with diarrhea at diagnosis (p = 0.015), weight loss at diagnosis (p = 0.038), Ki
      67 level (p = 0.025), stage of disease at diagnosis (p = 0.012), presence of
      liver metastases at follow-up (p = 0.005), presence of diffuse metastases at
      diagnosis (p = 0.005) and at follow-up (p = 0.007), and type of surgical approach
      (overall: p = 0.018; not operated vs. radical surgery: p = 0.008; not operated
      vs. palliative surgery: p = 0.045). Using multivariate analysis, only female
      gender (p = 0.012) and the presence of liver metastases at follow-up (p = 0.004)
      were significantly related to survival. CONCLUSION: In the present study, female
      gender and the appearance of liver metastases at follow-up seem to be the main
      conditions which determine the poor prognosis of patients with ileal endocrine
      tumors.

PMID- 17016033
TI  - Non-Hodgkin lymphoma and pesticide exposure: 25 years of research.
AB  - Over the past 40 years, a substantial rise in the incidence of non-Hodgkin
      lymphoma (NHL) has been observed. Epidemiologic studies aimed at understanding
      this rise have revealed some association with occupational exposure. NHL is
      common among farmers, where pesticides have been described as the culprit. The
      association between pesticides and NHL has been demonstrated mainly in case
      control studies, while retrospective cohorts have been less convincing.
      Pesticides including chlorphenol and phenoxyacetic acid herbicides,
      organochlorines, and organophosphate insecticides, carbamates, and fungicides
      have been associated with NHL. Although the causality has not been clearly
      proven, both genotoxic and nongenotoxic mechanisms for lymphomagenesis have been
      proposed. The leveling-off of NHL incidence in certain countries may be the
      result of a favorable change in pesticide usage patterns. Future studies, such as
      the Agricultural Health Study, may clarify the uncertainties regarding this
      issue.

PMID- 17016034
TI  - Ibandronate for the treatment of hypercalcemia or nephrocalcinosis in patients
      with multiple myeloma and acute renal failure: Case reports.
AB  - Multiple myeloma disrupts calcium homeostasis by a variety of mechanisms,
      including bone destruction and resorption. This causes hypercalcemia. When left
      untreated, hypercalcemia leads to nephrocalcinosis, impairment of kidney
      function, and eventually renal failure. Some degree of renal dysfunction is
      common in myeloma patients. Here, we report case studies showing the efficacy and
      renal safety of the single-nitrogen bisphosphonate, ibandronate, for the
      treatment of hypercalcemia and/or nephrocalcinosis in multiple myeloma patients
      hospitalized with acute renal failure. Patients (n = 7) received either one or
      two intravenous infusions of ibandronate (2-6 mg). Ibandronate was well tolerated
      in all patients and returned elevated blood calcium levels to normal. Renal
      function improved for all patients and normalized in 3/7 patients. We conclude
      that ibandronate is involved in rapidly improving or restoring acute renal
      function and calcium levels to within the normal range in this patient
      population. To clarify the exact value of ibandronate, further investigation is
      warranted in randomized prospective trials.

PMID- 17016035
TI  - Effect of protein kinase C on T lymphocyte proliferation and apoptosis in acute
      idiopathic thrombocytopenic purpura.
AB  - Previous studies have shown that T lymphocyte proliferation and apoptosis are
      abnormal in idiopathic thrombocytopenic purpura (ITP) children; however, the
      underlying regulated mechanisms in signal transductions remain unknown. In this
      paper, we investigated the changes of protein kinase C (PKC) activity in
      peripheral blood T lymphocytes and the effect of PKC on the peripheral blood T
      lymphocyte proliferation and apoptosis in ITP children. We demonstrated that T
      lymphocytes from ITP children were more susceptible to the activator (phorbol
      myristate acetate) and the inhibitor (H-7) of PKC. In ITP children, phorbol
      myristate acetate and H-7 dramatically affected T lymphocyte proliferation and
      apoptosis, but altered little in healthy children. Compared with healthy
      children, PKC activity was significantly enhanced in ITP children, increasing the
      expressions of Fas ligand on CD3+, CD4+ and CD8+ T cells, indicating positive
      correlations between PKC activity and the expressions of Fas ligand on T cells,
      while the relations between PKC activity and platelet count showed negative
      correlations. Taken together, our findings suggest that PKC signal transductions
      may participate in the procedure of T lymphocyte proliferation and apoptosis in
      ITP children. PKC activation may enhance T lymphocyte activity, suppress T cell
      apoptosis, and be involved in thrombocyte damage, which can be related to the
      immunity pathogenesis of ITP.

PMID- 17016036
TI  - Immunoregulatory T cells in the peripheral blood of patients with Hodgkin's
      lymphoma.
AB  - We aimed at investigating the distribution of various types of immunoregulatory T
      cells in the peripheral blood of patients with Hodgkin's lymphoma (HL) (n = 94)
      being in the state of long-lasting complete remission using flow cytometry.
      Healthy patients (n = 41) as 'negative' and patients in complete remission with
      breast cancer (n = 47) as 'positive' controls were investigated in the study. We
      found significant elevations in the number of CD4+ CD25high naturally occurring
      regulatory T cells, CD4+/intracellular IL-10+ (Tr1) and CD8+/intracellular IL-10+
      T cells in HL compared to the healthy controls. In carcinoma patients, however,
      the number of Tr1 and CD8+/IL-10+ T cells was higher than that in the other two
      groups. The increase in the number of CD4+ CD25high T cells seems to be
      characteristic of HL compared to the two other types of regulatory T cells. This
      change exists for a long time and it seems to be a characteristic of HL and
      independent of the types of therapy and the duration of time since therapy.

PMID- 17016037
TI  - Flow cytometry as a diagnostic tool for hereditary spherocytosis.
AB  - Flow cytometric analysis of eosin-5'-maleimide-labeled red blood cells has been
      proposed as a new method of identifying hereditary spherocytosis (HS). The aim of
      the present study was to analyze sensitivity and specificity of this method. Red
      blood cells from patients with HS (n = 58) revealed significantly lower mean
      channel fluorescence values than red blood cells from normal subjects (n = 110),
      unaffected HS family members (n = 8), and patients with other anemias (n = 44).
      Taking a mean channel fluorescence of 400.0 units as the threshold value
      identified by logistic regression, sensitivity and specificity of the test for HS
      were 96.6 and 99.1%, respectively. Flow cytometric analysis is a valuable
      screening test for the diagnosis of HS.

PMID- 17016038
TI  - Assessment of 8-methoxypsoralen and ultraviolet a light effects on human stroma
      generation and function.
AB  - Photopheresis or extracorporeal photochemotherapy (ECP) is a new immunomodulatory
      therapy in which a patient's leukocytes are exposed extracorporeally to 8
      methoxypsoralen (8-MOP) and ultraviolet A (UVA) light. Although it is used for
      the treatment of cutaneous T cell lymphoma, graft-versus-host disease, and
      several autoimmune diseases, with efficacy and safety reported in almost all
      studies, the mechanisms by which ECP exerts its beneficial effects are still
      unclear. As cellular targets of this procedure are numerous, we investigated the
      effects of 8-MOP and UVA light on stromal precursors and mature stromal layers.
      Human bone marrow stromal cell layers were established in long-term bone marrow
      culture medium from normal marrow mononuclear cells. Normal marrow mononuclear
      cells were incubated with 8-MOP and/or exposed to UVA light (PUVA treatment)
      before culturing. A control without 8-MOP and UVA was also included in the study.
      Apoptosis induction was evaluated using annexin V following 7 days after PUVA.
      After 4-6 weeks of culture, stromal layers were examined under a phase-contrast
      microscope to identify structural differences between PUVA-treated and control
      stroma. To determine whether PUVA treatment affected stromal regulation of
      adherent hematopoietic cell survival, mature stromal layers, incubated with 8-MOP
      and exposed to UVA light, were cocultured with nonadherent mononuclear cells from
      normal marrow. After 24 h, the percentage of apoptotic hematopoietic cell
      precursors was quantified by flow cytometry. This study provides evidences that
      the in vitro exposure of human stromal cell precursors to UVA light, in the
      presence of 8-MOP, inhibits stromal layer generation by inducing apoptosis, as
      evidenced by annexin V staining following 7 days of culture. Here, we show an
      additional cell target for this psoralen following UVA irradiation. However, in a
      second set of experiments, PUVA treatment did not affect the stromal capacity to
      support hematopoiesis in culture. Our results can contribute to a better
      definition of ECP mechanisms of action for future development of experimental
      designs and clinical applications of this intriguing procedure.

PMID- 17016039
TI  - Unusual extramedullary hematopoiesis in a patient receiving granulocyte colony
      stimulating factor.
AB  - A 42-year-old woman was diagnosed with myelodysplastic syndrome with fibrosis
      that developed bilaterally, cervical lymphadenopathy and cutaneous infiltration
      by trilineage extramedullary hematopoiesis after granulocyte colony-stimulating
      factor therapy because of severe neutropenia. Hepatosplenomegaly was not observed
      during her follow-up. Extramedullary hematopoiesis disappeared after growth
      factor therapy was stopped. Although the neutropenia was alleviated by growth
      factor administration, the appearance of an unusual involvement of extramedullary
      hematopoiesis should be kept in mind.

PMID- 17016040
TI  - Bortezomib-induced rhabdomyolysis in multiple myeloma.
AB  - Although multiple myeloma (MM) remains an incurable disease, its treatment has
      improved over the past decade. This improvement has been at least in part due to
      the introduction of novel antimyeloma agents with new mechanisms of action,
      including those that target both myeloma cells and the tumor microenvironment,
      with antiangiogenic and immunomodulatory properties. Among these drugs,
      bortezomib (Velcade), a selective proteasome inhibitor, has been approved for the
      treatment of relapsed and refractory MM patients after one line of therapy. The
      toxicity profile of bortezomib includes gastrointestinal symptoms, fatigue,
      thrombocytopenia, peripheral neuropathy, postural hypotension, as well as some
      uncommon events. A patient with relapsed MM who developed recurrent bortezomib
      induced rhabdomyolysis is reported. To our knowledge, this adverse event has not
      been previously described is this context.

PMID- 17016041
TI  - Rapid progression of Myelodysplastic syndrome to acute myeloid leukemia on
      sequential azathioprine, IFN-beta and copolymer-1 in a patient with multiple
      sclerosis.
AB  - A woman with relapsing-remitting multiple sclerosis (MS) was treated with oral
      azathioprine (AZA) for 4 years and subsequently switched to interferon-beta1a.
      Five years later, leukopenia developed and resolved after interferon was
      discontinued; MS treatment was changed to copolymer-1. Recurrent pancytopenia
      subsequently led to diagnosis of myelodysplastic syndrome (MDS) with deletion of
      the long arm of chromosome 5 (MDS 5q-). Within several months, unusually rapid
      for this subtype, MDS progressed to secondary acute myeloid leukemia. While AZA
      is the probable cause for the chromosomal deletion and MDS, combined or
      sequential immunomodulatory therapies may permit clonal expansion of malignant
      hematopoietic progenitors.

PMID- 17016042
TI  - Atypical chronic myeloid leukaemia with CD117-positive blast cells treated with
      imatinib: A report of two cases.

PMID- 17016043
TI  - Absence of BH3 domain mutations in the proapoptotic Bcl-2 gene family in non
      Hodgkin lymphomas.

PMID- 17016044
TI  - Identification of an acute basophilic leukaemia carrying a rare e6a2 BCR-ABL
      transcript.

PMID- 17016045
TI  - Mesenchymal stem cells derived from human chorionic plate may promote
      hematopoietic differentiation of the human embryonic stem cell line SNUhES3.

PMID- 17016046
TI  - Value of mean corpuscular volume and mean corpuscular haemoglobin in screening
      for beta-thalassaemia trait.

PMID- 17016047
TI  - Bortezomib-induced skin lesion.

PMID- 17016048
TI  - Another case of paraneoplastic cutaneous syndrome preceding indolent mantle cell
      lymphoma.

PMID- 17016049
TI  - The single nucleotide polymorphisms of I(Ks) potassium channel genes and their
      association with atrial fibrillation in a Chinese population.
AB  - Recent studies suggest that genetic mutation of the slow delayed rectifier
      potassium channel (I(Ks)) may underlie atrial fibrillation (AF). We investigated
      the association between AF and the single nucleotide polymorphisms (SNPs) of
      genes KCNQ1, KCNE1 and KCNE4 associated with this channel. Common non-synonymous
      SNPs in KCNQ1 and KCNE1 known to be frequent in Asian people were selected and
      direct sequencing of KCNE4 was performed to identify possible SNPs. The AF group
      consisted of 142 hospitalized patients with AF, the community control group
      consisted of 120 subjects, and a ward control group consisted of 118 hospitalized
      patients without AF. Restriction fragment length polymorphism analysis was
      performed to determine the genotypes. The minor allele frequencies of P448R,
      R519H, G643S for KCNQ1 and G38S and D85N for KCNE1 in the AF group, the community
      control group and the ward control group were 9.9, 7.9, 9.3%; 0, 0, -; 4.3, 4.2,
      1.7%; 28.4, 31.7, 29.7%; 0.7, 0.4%, -, respectively. There was no significant
      association between these SNPs and AF phenotype. There were eight SNPs in the
      whole length of KCNE4 plus 1,000 bases upstream of this gene including the non
      synonymous SNP E145D. Logistical regression analysis revealed a difference in the
      distribution of KCNE4 E145D in the AF and the community control group (minor
      allele frequency was 34.0 versus 27.1% respectively, OR = 1.66, p = 0.044). We
      provided the frequencies of non-synonymous SNPs of KCNQ1 and KCNE1 in Chinese
      population; none of these SNPs was associated with AF. But KCNE4 E145D may be
      associated with the AF phenotype.

PMID- 17016050
TI  - Methylene blue decreases ischemia-reperfusion (I/R)-induced spinal cord injury:
      an in vivo study in an I/R rabbit model.
AB  - OBJECTIVES: To evaluate the effects of intravenous methylene blue (MB)
      administration on ischemia-reperfusion (I/R) injury of the spinal cord (SC).
      METHODS: 16 rabbits were randomly assigned either to group M (n = 8; receiving
      MB, intervention group) or group C (n = 8; control group) and underwent a 30-min
      period of SC ischemia by clamping the abdominal aorta between the left renal
      artery and the aortic bifurcation. 15 min before clamping, rabbits received
      either intravenous MB (10 mg/kg; group M) or normal saline (group C). The two
      groups were compared 24 h postoperatively both histologically and for
      neurological function, using a Tarlov score. Measurements to determine levels of
      malondialdehyde (MDA) and glutathione (GSH) in the SC tissue were also performed.
      RESULTS: Neurological impairment and spinal tissue MDA levels were significantly
      lower in animals treated with MB (p < 0.001). In contrast, spinal GSH levels were
      significantly higher in group M (p < 0.001). Histological examination revealed
      that the integrity of the SC was better preserved in the MB group, whereas cords
      from the control group exhibited evidence of acute neuronal injury. CONCLUSIONS:
      The prophylactic use of MB reduces neurological injury and improves clinical
      outcomes in the rabbit SC I/R model. These effects are probably mediated by the
      drug's antioxidant properties.

PMID- 17016051
TI  - Didelphic uterus and obstructed hemivagina: recurrent hematometra in spite of
      appropriate classic surgical treatment.
AB  - We report the case of a young girl with uterus didelphys, obstructed vagina and
      ipsilateral renal agenesis treated by diagnostic laparoscopy and resection of the
      vaginal septum by a vaginal approach in order to drain the distended uterus.
      Despite classic surgery, the myometrium on the treated side never recovered its
      normal function, with subsequent persistence of recurrent hematometra.
      Laparoscopic subtotal hemihysterectomy had to be performed to avoid retention of
      hematometra and secondary pelvic inflammatory disease.

PMID- 17016052
TI  - The association of colour flow Doppler sonography and conventional
      ultrasonography improves the diagnosis of thyroid carcinoma.
AB  - OBJECTIVE: In the present study, we compared the results of conventional
      ultrasonography (US) and colour flow Doppler sonography (CFDS) with those of US
      guided fine needle aspiration biopsy (FNAB) and of pathologic staging of resected
      thyroid nodules, to assess the relative importance of US and CFDS in
      discriminating malignant thyroid nodules. SUBJECTS AND STUDY DESIGN: We
      retrospectively reviewed records of 230 patients submitted to US-guided FNAB
      before surgery for solitary, not hot thyroid nodules. Before US guided FNAB, they
      were examined with conventional US and CFDS. Conventional US evaluated nodule
      size, echogenicity, presence of halo sign and microcalcifications. CFDS evaluated
      the vascular pattern classified as types I, II and III. Twenty-seven patients
      with inadequate cytology were excluded from this study (11.7%). RESULTS: Two
      hundred and three patients underwent surgery. At histology a thyroid carcinoma
      was found in 36 patients (17.7%) and a benign nodule was observed in 167 patients
      (82.3%). We did not find any difference in cancer prevalence between nodules with
      a primary tumour size < or =1 cm and those >1 cm (17.6 vs. 17.7%; p = 0.99). A
      solid echo texture was not statistically significant to suggest malignancy (p =
      0.32). Microcalcifications were seen in 83.3% (30/36) of malignant nodules and in
      33.5% (56/167) of benign nodules. These results were statistically significant (p
      < 0.0001). The type III flow as determined by CFDS was a statistically
      significant criterion to suggest malignant disease (p < 0.005). The most
      predictive findings of malignancy on conventional US was the combination of
      microcalcifications plus the absence of halo sign (sensitivity 75%, specificity
      71.9%, p < 0.0001). The combination of an absence of halo sign on conventional US
      and a type III pattern on CFDS presented the higher sensitivity (83.3%) for
      malignancy with a specificity of 43.7%. Microcalcifications on US in combination
      with a type III CFDS pattern showed a lesser sensitivity (80.6%) with an improved
      specificity (75.4%). In our opinion, the better balanced combination of US and
      CFDS features was the absence of halo sign plus microcalcifications and a type
      III CDFS pattern (sensitivity 72.2%, specificity 77.2%). CONCLUSIONS: The
      combination of conventional US and CFDS provides benefits in increasing the
      screening sensitivity and accuracy in distinguishing malignant thyroid nodules.

PMID- 17016053
TI  - Modulation of the immune system by human rhinoviruses.
AB  - Human rhinoviruses (HRV) are the major cause of the common cold, one of the most
      frequent infectious diseases in humans. Though HRV infections of the upper
      respiratory tract are usually rather harmless, there is increasing evidence that
      HRV sets the stage for more dangerous pathogens, elicits asthmatic exacerbations,
      severe diseases in the lower respiratory tract and even autoimmunity. The
      pathogenic mechanisms of HRV infections leading to such complications are still
      poorly understood. It is a common strategy of pathogens to manipulate our immune
      system in order to evade an efficient immune response. A major characteristic of
      HRV is a high degree of species specificity. Thus, analyzing the potential immune
      evasion mechanisms used by HRV will be helpful for a better understanding of the
      pathogenesis of the common cold and may contribute to a better understanding of
      the human immune system as well. In this review we want to illuminate what is
      known about potential immune escape mechanisms used by HRV and discuss how such
      disturbances might lead to a suppressed and dysregulated immune competence in
      man.

PMID- 17016054
TI  - Standardization of an ash (Fraxinus excelsior) pollen allergen extract.
AB  - BACKGROUND: Ash tree (Fraxinus excelsior) is the main representative of the
      Oleaceae family in temperate zones. Diagnosis of ash pollen allergy is made
      difficult due to (1) an overlapping pollinization period with Betulaceae, (2) non
      inclusion in current diagnostic assays, and (3) some cross- reactivity with minor
      allergens from Betulaceae. The aim of this study was to calibrate an ash pollen
      in-house reference preparation (IHRP) in allergic patients in order to produce
      standardized products for diagnosis and immunotherapy purposes. METHODS: Ash
      pollen IHRP was extracted, ultrafiltered and freeze dried. Allergens in the
      extract were detected after 2-dimensional PAGE using specific sera and a
      monoclonal antibody. The Fra e 1 content of IHRP was evaluated by quantitative
      immunoprint. Forty-eight subjects from the North-East of France exhibiting
      clinical symptoms, a positive skin test and specific IgE levels > or =class 2 to
      ash pollen were recruited. IgE immunoprints were performed to select patients
      sensitized to the ash Fra e 1 allergen as opposed to cross-reacting allergens.
      Serial 10-fold dilutions of the IHRP were tested by skin prick tests in order to
      determine the concentration inducing a geometrical mean wheal diameter of 7 mm,
      said to correspond to an index of reactivity (IR) of 100 per millilitre. RESULTS:
      IgE-reactive molecules in IHRP comprise Fra e 1, Fra e 2, a 9-kDa molecule
      (presumably Fra e 3), as well as a doublet at 15 kDa and high molecular weight
      allergens. The 100 IR concentration of IHRP inducing a geometrical mean wheal
      diameter of 7 mm in 22 patients sensitized to Fra e 1 corresponds to the 1/126
      (w/v) extraction ratio (i.e. 259 microg/ml of protein by Bradford) and contains
      17 microg/ml of Fra e 1. The variability in total activity of 5 batches of
      standardized extracts was found to be significantly reduced when compared with 7
      non-standardized extracts. CONCLUSION: An ash pollen IHRP was defined and
      molecularly characterized. Its successful standardization at 100 IR/ml in
      patients specifically sensitized to Fra e 1 allowed a skin reactivity-based
      calibration in properly diagnosed patients. Such a standardized ash pollen
      extract is a reliable tool to support immunotherapy of ash pollen allergy.

PMID- 17016055
TI  - High vascular endothelial growth factor levels in NZW mice do not correlate with
      collagen deposition in allergic asthma.
AB  - BACKGROUND: Eosinophils contribute to the early features of allergic lung
      inflammation through the generation and release of a plethora of mediators.
      Eosinophil peroxidase (EPO) is one of the eosinophil granule proteins involved in
      the early response, but its participation in airway remodeling is not
      established. The present study addressed this question comparing an EPO-deficient
      mouse strain (NZW) with BALB/c and C57Bl/c strains. METHODS: Mice were immunized
      with ovalbumin/alum, challenged twice with ovalbumin aerosol, and lung responses
      were measured at day 22 or 28. Collagen, mucus and eosinophils were determined in
      lung sections stained with picrosirius, periodic acid-Schiff or hematoxylin
      eosin; transforming growth factor-beta and vascular endothelial growth factor
      were determined by ELISA, lipid bodies by enumeration in osmium-stained
      eosinophils, and airway reactivity to methacholine in isolated lung preparations.
      RESULTS: NZW mice showed significantly less collagen around bronchi and blood
      vessels, less mucus and less eosinophils around bronchi. Eosinophil lipid body
      formation and airway hyperreactivity were comparable among strains. Levels of
      transforming growth factor-beta were also comparable; however, the NZW mice
      showed much higher levels of vascular endothelial growth factor, even under basal
      conditions. CONCLUSIONS: In allergic lung inflammation, the combination of EPO
      deficiency and overexpression of VEGF found in NZW mice is associated with less
      collagen deposition, less mucus and reduced tissue eosinophilia. Eosinophil
      activation and airway hyperreactivity in NZW mice were similar to the other
      strains.

PMID- 17016056
TI  - Mechanism of inflammation in murine eosinophilic myocarditis produced by adoptive
      transfer with ovalbumin challenge.
AB  - BACKGROUND: Interleukin (IL)-5, RANTES and CC chemokine receptor 3 (CCR3) are
      essential for induction of eosinophil recruitment in organs, but the precise
      pathogenesis of eosinophilic myocarditis is still unclear. We investigated the
      relationships between these cytokines and receptors in the development of
      inflammation in murine myocarditis produced by adoptive transfer, with reference
      to eosinophil infiltration and signal transduction. METHODS: The splenocytes from
      male donor DBA/2 mice were separated after ovalbumin (OVA) sensitization. These
      cells had a CD4/CD8 ratio of approximately 3.0. Cells (2.0 x 10(7)) were
      individually transfused to recipient adoptive male DBA/2 mice, and OVA challenge
      was performed serially. The heart and spleen of the recipient were analyzed to
      determine the kinetics of IL-5, RANTES, CCR3 and eosinophil production with
      simultaneous determination of Janus kinase 3 (JAK3) mRNA. RESULTS: Approximately
      85% of recipient mice developed myocarditis; 35% had recognizable cell
      infiltration in the left ventricular endocardium, an effect which was absent in
      control mice. Eosinophilic myocarditis was usually associated with animals having
      several degenerative changes in myocardial cells, and IL-5, RANTES and CCR3
      expressions were usually present in these eosinophils (p < 0.05). CCR3 and JAK3
      mRNAs were detected in the spleens and hearts of recipient animals providing
      histological evidence for kinetics related to eosinophil infiltration.
      CONCLUSION: The murine model of adoptive transferred myocarditis is suitable for
      studying the mechanism of eosinophilic myocarditis. A unique pathogenesis of this
      disorder may be controlled by the synergism of CD4 dominancy in the donor and JAK
      STAT signaling in the recipient, which may cause recruitment of eosinophils into
      heart lesions.

PMID- 17016058
TI  - Mechanisms of aspirin-sensitive respiratory disease--a two-compartment model.

PMID- 17016057
TI  - Genetic impact of functional single nucleotide polymorphisms in the 3'-UTR region
      of the chemoattractant receptor expressed on Th2 cells (CRTH2) gene on asthma and
      atopy in a Japanese population.
AB  - BACKGROUND: The human chemoattractant receptor expressed on Th2 cells (CRTH2),
      the receptor for prostaglandin D2, induces cell migration in eosinophils,
      basophils, and Th2 cells. The gene encoding CRTH2 is located on chromosome 11q13.
      Several groups, including ours, have reported significant associations between
      this region and various traits associated with allergic diseases such as asthma
      and atopy. Two single nucleotide polymorphisms in the 3'-UTR of the CRTH2 gene
      (1544G-->C and 1651G-->A) are associated with the mRNA stability of the gene;
      they have also been associated with asthma in both African American and Chinese
      populations. METHODS: Because CRTH2 is a biologically important candidate gene on
      chromosome 11q13, we conducted a case-control analysis using 787 Japanese
      subjects (384 asthmatics and 403 controls) to evaluate the genetic impact of the
      CRTH2 gene on asthma and asthma-related traits. Four polymorphisms [1544G-->C
      (rs11571288), 1651G-->A (rs545659), 11336T-->C (rs2074422), and 12375G-->T
      (rs561285)] were studied. RESULTS: The allele, genotype, or haplotype frequencies
      for 2 functional polymorphisms in our Japanese population were significantly
      different from those in the Chinese or African American populations. No
      association was found between any polymorphisms or haplotypes in the CRTH2 gene
      and asthma, atopy, or total serum IgE levels in a Japanese population.
      CONCLUSIONS: Our data failed to support previous associations of functional
      polymorphisms at the 3'-UTR of the CRTH2 gene implicated in asthma. We did show a
      significant difference in the allele and genotype frequencies as well as
      different haplotype frequencies among African American, Chinese, and Japanese
      populations, suggesting that the genetic impacts of these functional
      polymorphisms on asthma and asthma-related phenotypes may vary in different
      populations.

PMID- 17016059
TI  - Safety of meloxicam in aspirin-hypersensitive patients with asthma and/or nasal
      polyps. A challenge-proven study.
AB  - BACKGROUND: The anti-inflammatory actions of acetylsalicylic acid (ASA)/non
      steroidal anti-inflammatory drugs (NSAIDs) are thought to be due to inhibition of
      COX-2, whereas the side effects such as gastric damage and aspirin-induced asthma
      are mediated through inhibition of COX-1. Therefore, a new class of drugs with
      COX-2 selectivity may be well tolerated by patients with ASA/NSAIDs
      hypersensitivity. OBJECTIVE: We investigated whether subjects with asthma and/or
      nasal polyps (NP) and analgesic intolerance proven by oral ASA provocation test
      tolerated the selective COX-2 inhibitor, meloxicam. METHODS: All subjects were
      first challenged with ASA using a 2-day, single-blind, placebo-controlled oral
      provocation test. Thereafter, the subjects showing positive response to ASA
      provocation underwent a single-blind, placebo-controlled challenge with a
      cumulative dose of 7.5 mg of meloxicam on 2 separate days. One and three fourths
      of the divided doses of placebo and the active drug were given at 1-hour
      intervals. Clinical symptoms, lung function, and blood pressure were monitored
      during these challenge protocols. RESULTS: Twenty-one patients with asthma and/or
      NP (10 males and 11 females; mean age: 38.4 +/- 2.9 years) who reacted to ASA
      challenges were enrolled in the study. Response to ASA provocation was rhinitis +
      bronchospasm in 13, and extrabronchial reactions in 8 (isolated rhinitis in 3)
      patients. Mean PD(20) was 163.4 +/- 39.9 mg ASA among patients who reacted with
      bronchospasm to ASA. Only 1 patient reacted to meloxicam challenge at a
      cumulative dose of 7.5 mg. CONCLUSION: This study indicates that 7.5 mg of
      meloxicam is a safe alternative treatment for ASA-hypersensitive asthma and/or NP
      patients with proven hypersensitivity via oral ASA challenges.

PMID- 17016060
TI  - Long-lasting effects of sublingual immunotherapy for house dust mites in allergic
      rhinitis with bronchial hyperreactivity: A long-term (13-year) retrospective
      study in real life.
AB  - BACKGROUND: Subcutaneous immunotherapy for respiratory allergy has shown a long
      lasting efficacy after its discontinuation, whereas evidence in the case of
      sublingual immunotherapy (SLIT) is weak. This retrospective study evaluates
      whether SLIT exerts a long-lasting effect and whether it relates to its duration.
      METHODS: Sixty-five patients allergic to mite and positive to methacholine
      challenge 13 years ago were studied. Twelve (control group, SLIT 0) were treated
      for 4 years only with standard pharmacological therapy (SPT), while 53 received
      SLIT and SPT. Among these, four groups were identified according to SLIT
      duration. Fifteen patients were treated for 1 year (SLIT 1), 10 for 2 (SLIT 2),
      14 for 3 (SLIT 3) and 14 for 4 years (SLIT 4). Clinical parameters (symptom
      monthly score, SMS), bronchial reactivity and FEV1 were evaluated in 1992 (run
      in), 1993 (baseline) and every 2 years from 1997 to 2005. RESULTS: Two to 3 years
      after the treatment ended, a positive effect on SMS, but not methacholine
      challenge and FEV1, was seen in the SLIT groups versus SLIT 0. At this time
      interval an effect on methacholine challenge was also seen in SLIT 3. After 7-8
      years a significant difference was seen for SMS, i.e., it was significantly
      better in SLIT 4 than in the other groups, while bronchial reactivity was still
      improved in SLIT 1, 3 and 4 only after 5-6 years. CONCLUSIONS: The effects of a 4
      year SLIT on clinical parameters but not bronchial reactivity and FEV1 last 7-8
      years after its discontinuation. SLIT shorter than 4 years yields proportionally
      less impressive results.

PMID- 17016061
TI  - The prevalence of atopy in asthmatic children correlates strictly with the
      prevalence of atopy among nonasthmatic children.
AB  - BACKGROUND: Because asthma preferentially burdens persons with atopy, atopy is
      simplistically considered a primary 'cause' of asthma. Yet at the population
      level, the percentage of asthma cases 'attributable' to atopy ranges from less
      than 10% to more than 60%. Seeking to understand the rationale for the
      variability of atopy-attributable cases of asthma, we systematically reviewed the
      results of our own previous epidemiological studies and several studies conducted
      by others in children. METHODS: From each of the 37 random pediatric populations
      selected by a Medline search combining the key words 'IgE or skin tests or
      hypersensitivity, immediate' with 'epidemiological studies, cross-sectional, case
      control, prevalence, longitudinal, epidemiology of asthma' (12 from our previous
      pediatric surveys and a further 25 reported from 19 studies in children), we
      extracted the population prevalence of asthma and atopy among asthmatic subjects
      and among the nonasthmatic part of the population. RESULTS: No correlation was
      found between the prevalence of asthma (range 1.8-44.1%) and atopy (range 5.8
      63.9%) in these 37 populations of children (r = 0.052, p = 0.761). Nevertheless,
      the prevalence of atopy among asthmatics strictly correlated with the prevalence
      of atopy in nonasthmatics (r = 0.900, p < 0.001, slope 1.364). CONCLUSION: The
      prevalence of asthma and atopy varies worldwide and at various time points and
      independently undergoes the influence of powerful environmental factors. The
      almost perfect correlation we found between atopy in asthmatics and atopy in the
      nonasthmatic part of the childhood population shows that the prevalence of atopy
      in asthma depends on environmental factors that simultaneously induce atopy in
      asthmatic and nonasthmatic subjects.

PMID- 17016062
TI  - New evidence of H1-receptor independent COX-2 inhibition by fexofenadine HCl in
      vitro.
AB  - BACKGROUND/AIMS: Fexofenadine HCl (FEX) has previously been shown to have anti
      inflammatory properties in relieving nasal congestion in allergic rhinitis. The
      objective of this study was to further elucidate the mechanism of action behind
      the anti-inflammatory properties of FEX in addition to its H(1)-receptor
      antagonism. METHODS: The effects of two antihistamines, FEX and loratadine (LOR),
      were investigated on cyclooxygenase (COX)-1 and -2 enzymes in vitro. FEX (10(-9)
      10(-3) mol/l) and LOR (10(-9)-10(-4) mol/l) were incubated with arachidonic acid
      in a COX screening assay with either ovine COX-1 or COX-2 or human COX-2. COX-2
      enzyme inhibitory activity for the antihistamines was compared with the known
      selective COX-2 inhibitor DuP-679. RESULTS: High concentrations of FEX (10(-3)
      mol/l) significantly inhibited arachidonic acid-mediated ovine COX-1 activity,
      but low concentrations had no effect. Low concentrations of FEX (10(-8) mol/l)
      inhibited ovine COX-2 activity, and this inhibition decreased with increasing
      concentrations. The inhibition of COX-2 activity by FEX was similar to that seen
      with the selective COX-2 inhibitor, DuP-679. Conversely, LOR inhibited COX-1
      activity at low concentrations (10(-8) mol/l), but had little inhibitory effect
      on COX-1 at high concentrations. LOR (10(-5) mol/l) markedly stimulated COX-2
      activity. CONCLUSION: FEX showed selective arachidonic acid-mediated COX-2
      inhibitory enzyme activity, which differed markedly from the COX inhibitory
      enzyme activity of LOR. This selective COX-2 inhibitor activity by FEX may
      contribute to its anti-inflammatory properties in relieving nasal congestion in
      allergic rhinitis.

PMID- 17016063
TI  - In their shoes: Two nurses and a physician have been accused of murder during the
      Katrina disaster.

PMID- 17016064
TI  - What's an educator to do?

PMID- 17016084
TI  - Laboring in chains.

PMID- 17016085
TI  - Using seasonal influenza clinics for public health preparedness exercises.

PMID- 17016086
TI  - Avian influenza update.

PMID- 17016087
TI  - Influenza vaccination update.

PMID- 17016088
TI  - HIV and AIDS report from Toronto: the XVI International Conference on AIDS.

PMID- 17016089
TI  - Airborne infections and respirators.

PMID- 17016091
TI  - Massachusetts: expanding access to care.

PMID- 17016092
TI  - Sensory impairment in older adults: Part 1: Hearing loss.
AB  - Preserving older adults' sense of hearing and helping them to maintain
      communication in the face of changes that occur with age are areas of concern for
      nurses. In addition to reviewing the types of hearing impairment, this article
      emphasizes assessment strategies and interventions that nurses can use across
      settings. This is Part 1 of a two-part article on sensory impairment in older
      adults; in the November 2006 issue, Part 2 will address visual impairment in this
      population.

PMID- 17016094
TI  - Implementing a rapid response team.

PMID- 17016095
TI  - Home modification.
AB  - Almost 50 million Americans--about one in five--live with a mental or physical
      disability, many in homes that are inconvenient, restrictive, or dangerous for
      them. Modifying the home using universal (barrier-free) design, architectural
      accessibility, and other such concepts can reduce the risk of falls and improve
      overall function. Nurses can be involved by assessing patients' living quarters
      and recommending specific modifications.

PMID- 17016098
TI  - The Nightingale Metrics.
AB  - Staff nurses at Children's Hospital Boston worked together to identify what was
      important to the patients and families they cared for, measured how often nurses
      performed these interventions, and used the data to improve the care they
      provide. This initiative, the Nightingale Metric Project, can serve as a model
      for ongoing measurement and improvement of nursing care in all settings.

PMID- 17016100
TI  - Nursing home staffing standards.

PMID- 17016108
TI  - Should RNs be forced to get the flu vaccine?

PMID- 17016109
TI  - Harmonizing health. Interview by Hob Osterlund.

PMID- 17016112
TI  - Quadriceps contusions: clinical results of immediate immobilization in 120
      degrees of knee flexion.
AB  - OBJECTIVE: Quadriceps contusions often result in significant time loss and the
      possibility of myositis ossificans. The objective of this descriptive case series
      was to document the results of an initial treatment regimen instituted within 10
      minutes from the time of the injury. DESIGN: This study was a prospective case
      series of 47 midshipmen who sustained quadriceps contusions between August 1987
      and December 2005 and who were treated identically and followed by serial
      examinations until the return to unrestricted full athletic activities. SETTING:
      United States Naval Academy (USNA), Annapolis, Maryland. PARTICIPANTS: USNA
      midshipmen who sustained quadriceps contusions while participating in sports
      activities. Inclusion criteria were (1) stated inability at the time of the
      injury to continue participation and (2) the inability to perform a pain-free,
      isometric quadriceps contraction and maintain the knee in full extension with a
      straight leg lift. INTERVENTIONS: On diagnosis the knee was passively flexed
      painlessly to 120 degrees and held continuously in that position for 24 hours.
      Use of the brace was discontinued at 24 hours and the midshipman was instructed
      to perform active, pain-free quadriceps stretching several times a day and to
      perform pain-free isometric quadriceps strengthening exercises as soon as
      possible. Goals included pain-free knee flexion and quadriceps size and firmness
      equal to the uninjured side. MAIN OUTCOME MEASUREMENTS: Average time from the day
      of the injury to return to unrestricted full athletic activities with no
      disability. RESULTS: The average time to return to unrestricted full athletic
      activities with no disability was 3.5 days (range of 2 to 5 days). Radiographic
      examination of the first 23 midshipmen at 3 and 6 months following the injury
      revealed 1 case of myositis ossificans. CONCLUSIONS: Placing and holding the knee
      in 120 degrees of flexion immediately following a quadriceps contusion appears to
      shorten the time to return to unrestricted full athletic activities compared with
      reports in other studies.

PMID- 17016113
TI  - Patellar tendons with normal imaging and pain: change in imaging and pain status
      over a volleyball season.
AB  - OBJECTIVE: Patellar tendon injury commonly presents as abnormal imaging with pain
      or abnormal imaging without pain. Normal imaging with pain has also been reported
      clinically, but little is known about the behavior of these tendons over time.
      This study investigated the behavior of tendons with normal imaging and pain over
      a volleyball season. DESIGN: Prospective study. SETTING: Institutional.
      PARTICIPANTS: One hundred and one male and female volleyball players. MAIN
      OUTCOME MEASUREMENTS: At the beginning and end of the season ultrasound
      determined imaging status and the single leg decline squat test determined pain.
      The imaging and pain status at follow-up of tendons with normal imaging and pain
      at baseline was reported and contrasted to the imaging and pain status of the
      other patellar tendon injuries. RESULTS: Tendons with normal imaging and pain
      [relative risk (RR) 15.1], abnormal imaging without pain (RR 14.6), and abnormal
      imaging with pain (RR 51.5) had a greater risk of having abnormal imaging with
      pain at the end of the season when compared with normal tendons (P < 0.01). Among
      tendons with normal imaging and pain at baseline, 27% had abnormal imaging
      without pain and 21% contained abnormal imaging with pain at the end of the
      season. CONCLUSIONS: Patellar tendons with normal imaging and pain at the
      beginning of a volleyball season are equally as likely to have abnormal imaging
      and pain at the end of the season as tendons with abnormal imaging without pain.
      Normal imaging with pain may represent a clinically relevant patellar tendon
      injury.

PMID- 17016115
TI  - Effects of supervised treadmill-walking training on strength and endurance of the
      calf muscles of individuals with peripheral arterial disease.
AB  - OBJECTIVE: Supervised treadmill-walking training is an effective treatment to
      improve walking capacity for individuals with peripheral arterial disease (PAD).
      The primary aim of this study was to examine whether a supervised treadmill
      walking program would improve calf-muscle strength and endurance in individuals
      with PAD. DESIGN: The study included two stages. The first 12-week period was a
      nonexercise, within-subject control stage and the second 12-week period was an
      exercise training stage. SETTING: Southern Cross University, Australia. SUBJECTS:
      Twenty-two subjects with stable intermittent claudication were recruited. Their
      resting and postexercise ankle-to-brachial systolic blood pressure index (ABI)
      was 0.61 +/- 0.13 and 0.41 +/- 0.22, respectively. INTERVENTIONS: Subjects
      trained in the laboratory, 3 sessions per week for 12 weeks. OUTCOME
      MEASUREMENTS: Walking capacity, calf-muscle strength (peak torques in isokinetic
      plantar flexion at velocities of 30 degrees per second, 60 degrees per second,
      and 90 degree per second) and endurance (mean peak force, total work, and mean
      power in repeated maximal plantar flexions at 60 degrees per second), ABI, and
      peak oxygen uptake were measured at the baseline and the end of each stage.
      RESULTS: Analysis of variance (ANOVA) with repeated measures indicated that the
      supervised treadmill-walking program significantly increased calf-muscle strength
      and endurance. Walking capacity and peak oxygen uptake also showed significant
      improvements following the training program. Significant correlation was found
      between the improved calf-muscle endurance and walking capacity. CONCLUSION:
      Supervised treadmill exercise is highly effective in improving walking capacity.
      The improved walking capacity is accompanied by improved calf-muscle strength and
      endurance in individuals with PAD.

PMID- 17016114
TI  - Prevalence of bowlegs among child and adolescent soccer players.
AB  - OBJECTIVE: Little is known about the interactions of sports-related demands and
      human body, in particular on musculoskeletal features, during growth. Focusing on
      the relationship between soccer and lower limb alignment, we examined the
      hypothesis that varus knee deviation is more prevalent among high-performance
      pediatric and adolescent soccer players. DESIGN: Cross-sectional study with
      focused sampling. SETTING: First league sports clubs. PARTICIPANTS: 106 male
      child/adolescent soccer players aged 10 to 21 years and 68 age-matched tennis
      players. INTERVENTIONS: All athletes completed a demographic questionnaire and
      underwent physical examinations, which included height, weight, generalized
      laxity, knee, ankle, foot and spine axis, hip range of motion, tibial torsion, Q
      angle, foot navicular height, and progression angle. MAIN OUTCOME MEASUREMENT:
      Varus/valgus axis was determined by the intercondylar intermalleolar distance
      while standing. Soccer and tennis players were compared on knee axis and other
      outcome variables by analysis of covariance, adjusting for age and by t-tests
      within age groups. RESULTS: A significantly higher prevalence of knee varus was
      found among the soccer players compared to that among the tennis players. The
      difference in intracondylar distance was statistically significant after the age
      of 13 years (P < 0.001). In addition, compared to tennis players, soccer players
      had higher foot arches, decreased hip external rotation and increased external
      tibial torsion. CONCLUSIONS: Varus knee axis deviation was more common among
      children and adolescent soccer players than among tennis players. The prevalence
      was more pronounced among players aged 13 years or older. Further research is
      needed to explore the rationale of this phenomenon.

PMID- 17016116
TI  - Patterns of allergic reactivity and disease in Olympic athletes.
AB  - OBJECTIVE: Because the Sydney Olympic Games were being held in the spring, we
      wished to examine the prevalence of allergic disorders in the Australian Olympic
      and Paralympic athletes and to examine patterns of allergic reactivity and
      medication use for the treatment of allergic symptoms. DESIGN: A survey case
      series of Australian Olympic and Paralympic athletes. SETTING: Screening was
      conducted on team processing days. PARTICIPANTS: Prospective members of the
      Australian Olympic and Paralympic teams. INTERVENTION: A questionnaire seeking
      information on the presence of allergic disorders, symptoms, family history, and
      medication use was administered. Skin-prick tests (SPT) for sensitivity to common
      aeroallergens was performed. OUTCOME MEASURES: Athletes were classified as atopic
      or non-atopic, and patterns of reactivity were examined according to sporting
      category. RESULTS: Of the athletes, 56% had a positive SPT to at least 1
      allergen, with 34% reacting to at least 1 seasonal allergen. There was no
      significant association between skin test reactivity and sporting category. Of
      the athletes, 37% had allergic rhinoconjunctivitis (AR/C), whereas 24% had
      seasonal allergic rhinoconjunctivitis (SAR/C). Approximately one-third of all
      those with AR/C had a history of asthma, whereas approximately one-fifth had a
      history of atopic dermatitis. Swimmers were most likely to have asthma, AR/C, and
      positive skin tests to any allergen. Very few athletes with self-reported AR/C
      took any medication to relieve their symptoms. CONCLUSIONS: Allergic disorders
      are common among athletes from all sports. The known impact of AR/C on quality of
      life necessitates that it be screened for and managed appropriately.

PMID- 17016117
TI  - A community-based model for medical management of a large scale sporting event.
AB  - OBJECTIVE: To develop and assess a community-based model for medical coverage for
      a large multisport event. DESIGN: The model included pre-event risk
      stratification, a concise training program for all medical volunteers, and
      detailed medical control guidelines. Prospective data collection was performed
      using standardized injury reporting forms. SETTING: The 2005 World Masters Games
      in Edmonton, Alberta, Canada. PATIENTS: Approximately 21,600 athletes between the
      ages of 25 and 97 who were participants in the World Masters Games.
      INTERVENTIONS: A 4-category risk scale was developed and applied to each sport.
      Medical volunteers were provided intensive training and guided by concise medical
      control guidelines. Medical encounters were recorded using a standardized injury
      report form. MAIN OUTCOME MEASURES: Incidence of injury by sport. Rate of
      ambulance transportation. Rate of medication use. Relevance of medical control
      guidelines. RESULTS: Medical coverage for over 80 venues was provided by 243
      volunteers. A total of 1767 medical encounters were documented, with an overall
      injury rate of 8.2% (95% CI, 7.9 to 8.5). The majority of injuries were of a
      minor nature. Only 35 (0.16%) athletes had injuries that required medication or
      ambulance transportation. Cardiopulmonary resuscitation and defibrillation was
      required in only 1 patient. CONCLUSIONS: The risk of injury during the World
      Masters Games appears to be low, and the risk of severe injury is extremely low.
      The described community-based model for medical coverage for multi-sport events
      appears to be safe and practical.

PMID- 17016118
TI  - Heart rate variability, blood pressure variability, and baroreflex sensitivity in
      overtrained athletes.
AB  - OBJECTIVE: To assess the effects of abruptly intensified physical training on
      cardiovascular control. DESIGN: Retrospective longitudinal study. SETTING:
      Research laboratory. PARTICIPANTS: Ten healthy athletes (5 men and 5 women) from
      track and field as well as triathlon. INTERVENTIONS: A 2-week training camp,
      including daily stepwise increasing cycling tests, running of 40 minutes, and
      additional cycling of 60 minutes. MAIN OUTCOME MEASUREMENTS: Time and frequency
      domain parameters of resting heart rate and blood pressure variability (HRV and
      BPV) and baroreflex sensitivity (BRS), before, during, and after the training
      camp. RESULTS: We found significantly reduced HRV during the training camp (mean
      beat-to-beat interval: 1042 [937 to 1194] ms vs. 933 [832 to 1103] ms vs. 1055
      [947 to 1183] ms, P < 0.01; root-mean-square of beat-to-beat interval
      differences: 68 [52 to 95] ms vs. 52 [38 to 71] ms vs. 61 [48 to 78] ms, P <
      0.05). Further, BRS was significantly reduced: 25.2 (20.4 to 40.4) ms/mmHg vs.
      17.0 (12.9 to 25.7) ms/mmHg vs. 25.7 (18.8 to 29.1) ms/mmHg, P < 0.05. These
      effects disappeared at a large degree after 3 to 4 days of recovery. CONCLUSION:
      Abruptly intensified physical training results in an altered autonomic
      cardiovascular activity towards parasympathetic inhibition and sympathetic
      activation that can be monitored by means of HRV and BRS analyses and might
      provide useful markers to avoid the overtraining syndrome.

PMID- 17016119
TI  - Adequacies of skin puncture for evaluating biochemical and hematological blood
      parameters in athletes.
AB  - OBJECTIVE: The authors tested the effect of blood sampling (skin versus venous
      puncture) on some biochemical and hematological blood parameters in athletes to
      answer whether skin puncture could be used as a substitute for venous puncture.
      DESIGN: Comparative study of 2 methods of blood samples collection. SETTING: The
      blood was collected in the same athletes at 3 different moments of the
      preparatory training phase. PARTICIPANTS: Fourteen male indoor soccer players (22
      +/- 1 years old) and 7 female handball players (18 +/- 1 years old) participated.
      MAIN OUTCOME MEASUREMENT: Blood was collected in heparin and K3EDTA by Vacutainer
      BD or Microvette Sarstedt system for biochemical and hematological analyses,
      respectively. RESULTS: There were no significant statistical differences between
      the 2 methods for the values of creatine kinase, urea, creatinine, lymphocytes,
      and platelets. The other hematological analyzes and uric acid exhibited
      significant higher values in skin blood, although they were all within the normal
      expected range. A high degree of correlation was observed between the 2
      techniques for all parameters. CONCLUSIONS: Skin puncture is a reliable, easy,
      accurate, and less invasive sampling method for assessing hematological and some
      biochemical parameters in athletes, respecting that blood samples should always
      be obtained from the same site, especially in follow-up studies.

PMID- 17016120
TI  - Is physical exercise beneficial for persons with Parkinson's disease?
AB  - OBJECTIVE: To review existing studies evaluating the effectiveness of physical
      exercise on mortality, strength, balance, mobility, and activities of daily
      living (ADL) for sufferers of Parkinson's disease (PD). DATA SOURCES: The
      following databases were searched (1) Cochrane Database of Systematic Reviews,
      (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) PubMed
      and (4) Medline/NARIC (National Rehabilitation Information Center) using
      combinations of key words Parkinson's disease and physical exercise. Only
      articles written in English were included. References cited were also examined.
      STUDY SELECTION: Studies were eligible if (1) only patients with PD were included
      in the intervention study (there were many studies that evaluated the benefits of
      exercise after stroke, cardiac arrest, sports injuries, surgery, and arthritis,
      but only a few for patients with PD), (2) the intervention included some form of
      physical or therapeutic exercise, (3) the effects of the physical exercise were
      evaluated, and (4) the studies were published in a refereed journal. Because few
      studies were found that dealt with PD patients exclusively, all studies that
      evaluated the effectiveness of physical exercise for only PD patients were
      included. Seven studies met our criteria and were selected. Three of the selected
      studies were randomized controlled studies, 1 was an open trial, and the other 3
      relied on patients' own assessments. DATA SYNTHESIS: Outcomes in the studies were
      measured in terms of physical improvements in patients with PD, such as improved
      axial rotation, functional reach, flexibility, balance, muscle strength, short
      step gait, and mobility. All studies reviewed show that exercise improves overall
      performance in PD patients. Improvements were measured using standardized tests
      and other measurement scales. CONCLUSIONS: The results of the present research
      synthesis support the hypothesis that patients with PD improve their physical
      performance and activities of daily living through exercise. Future studies
      should include the development of standardized exercise programs specific for
      problems associated with PD as well as standardized testing methods for measuring
      improvements in PD patients. There is also a need for longer term studies (over 1
      year) to assess if improvements achieved during the intervention stage are
      retained long term.

PMID- 17016121
TI  - Biceps tendon ruptures in rock climbers.

PMID- 17016122
TI  - Supracondylar femur fracture after endoscopic anterior cruciate reconstruction
      using an EndoButton.

PMID- 17016123
TI  - Cutaneous larva migrans in a beach soccer player.

PMID- 17016124
TI  - The extreme dragon boat tryout: a case report of acute exertional upper extremity
      rhabdomyolysis.

PMID- 17016125
TI  - Hyponatremia in marathon runners.

PMID- 17016126
TI  - Can exercise lower blood pressure in mildly hypertensive older persons?

PMID- 17016127
TI  - Corticosteroid injection compared with extracorporeal shock wave therapy for
      plantar fasciopathy.

PMID- 17016128
TI  - What treatment is most effective for acute Achilles tendon ruptures?

PMID- 17016129
TI  - IBS and autonomic nervous system responses to pain.

PMID- 17016130
TI  - Esophageal disease in scleroderma.
AB  - Progressive systemic sclerosis (PSS) causes smooth muscle atrophy and fibrosis of
      the distal two-thirds of the esophagus. Motility studies show reduced-amplitude
      or absent peristaltic contractions in this region and normal or decreased lower
      esophageal sphincter pressure. Patients complain of dysphagia, heartburn, and
      regurgitation due to reflux and dysmotility. Complications include strictures
      found in 17% to 29% of patients and Barrett esophagus is 0% to 37%. Candida
      esophagitis is a complication of PSS not seen with non-PSS reflux. Esophageal
      disease correlates with pulmonary involvement but not with disease in the stomach
      or intestines. Whether reflux contributes to the pulmonary disease is an open
      question. Although manometry is the gold standard for diagnosis, cine-esophagram
      and scintography are only slightly less sensitive and should be considered for
      following the patients. Symptoms correlate poorly with evidence of esophagitis or
      abnormal 24-hour pH recordings. As a result, it is unclear which patients should
      receive acid-reducing or prokinetic medications and which medication to use.
      Aspiration precautions are important in those with severe esophageal dysmotility.
      This review of the literature highlights many areas of uncertainty in the
      diagnosis and treatment of esophageal disease in PSS that can be addressed in
      clinical studies.

PMID- 17016131
TI  - Summary of probiotic activities of Bifidobacterium lactis HN019.
AB  - The bacterium, Bifidobacterium lactis HN019, has been studied for a variety of
      traits important to its ability to function as a probiotic. Publications
      documenting identity, safety, antipathogenic effects, immune enhancement, and
      intestinal colonization are reviewed. Most studies documenting immune effects are
      short term in duration (< or =6 wk feeding periods), so longer term trials would
      be useful to determine to what extent effects are sustained. One year-long trial
      feeding both galacto-oligosaccharides and HN019 in children 1 to 3 years of age
      provided evidence for improved growth and reduction in infection incidence. HN019
      is a well-characterized probiotic strain with documented probiotic effects of
      meaningful magnitude especially in the area of immune system modulation.

PMID- 17016132
TI  - Endoscopic techniques and management of foreign body ingestion and food bolus
      impaction in the upper gastrointestinal tract: a retrospective analysis of 139
      cases.
AB  - BACKGROUND: Ingested foreign bodies and food bolus impaction are frequently seen
      in endoscopic practice. Successful foreign body and food bolus removal may depend
      on the method used, the choice of device, and the experience level of the
      endoscopist, although few papers report experience and outcome of tertiary
      centers. AIM: To investigate the effectiveness of our protocol designed for
      removal of ingested foreign bodies and food boluses. METHODS: We retrospectively
      reviewed all patients with a diagnosis of foreign body ingestion and food bolus
      impaction from 1994 to 2005 identified by computer search. Patients were excluded
      if medical record was incomplete. RESULTS: The analysis included 171 patients.
      Foreign bodies and impacted food boluses were found in 77 and 62 patients,
      respectively. In 32 cases (23%), the foreign bodies passed spontaneously through
      the gastrointestinal tract. The overall success rate for endoscopic management
      was obtained in 137 patients (98.6%). Surgical removal of a foreign body was
      required in only 2 cases (1.4%). According to the type and location of the
      foreign object and food bolus we used Dormia baskets, retrieval forceps,
      polypectomy snares, and all sizes of Roth net. No complications relating to the
      endoscopic procedure were observed; 50 patients (35.2%) had an underlying
      esophageal disease. CONCLUSIONS: Endoscopic removal of upper gastrointestinal
      tract foreign bodies and food bolus impaction is efficacious and safe. Especially
      the Roth net is the best device for safe retrieval of food boluses and button
      disc batteries.

PMID- 17016133
TI  - Evaluation of four different fecal tests for determination of cure after
      Helicobacter pylori treatment.
AB  - BACKGROUND: Data evaluating the monoclonal tests for determination of cure after
      Helicobacter pylori treatment are scarce. GOALS: This study was aimed to evaluate
      the usefulness of 4 stool tests-2 new RAPID monoclonal immunochromatographic
      tests (RAPID Hp StAR, DakoCytomation, Cambridge, UK and ImmunoCard STAT! HpSA,
      Meridian Diagnostics, Cincinnati, OH) a monoclonal EIA test (Amplified IDEIA Hp
      StAR, DakoCytomation, Cambridge, UK), and a polyclonal EIA test (Premier Platinum
      HpSA, Meridian Diagnostics, Cincinnati, OH)-to confirm cure of H. pylori
      infection after eradication treatment. STUDY: Ninety-seven patients who underwent
      eradication treatment were included. Cure of H. pylori infection was determined
      using 2 consecutive reference tests. Fecal tests were performed according to the
      specifications of the manufacturer. Sensitivity, specificity, and positive and
      negative predictive values were calculated. RESULTS: After H. pylori eradication,
      the RAPID Hp StAR test has a sensitivity of 73% for detecting persistent
      infection, a specificity of 96% to 98%, a positive predictive value of 73% to 80%
      and a negative predictive value of 96%. For ImmunoCard STAT! HpSA the
      corresponding values were 91%, 97%, 77%, and 99%, for Amplified IDEIA Hp StAR
      73%, 97%, 73%, and 97%, and for Premier Platinum HpSA 91%, 79%, 35%, and 98%.
      CONCLUSIONS: All tests except Premier Platinum HpSA were highly accurate
      confirming eradication after treatment.

PMID- 17016134
TI  - Nonsteroidal anti-inflammatory drug use is a significant cause of peptic ulcer
      disease in a tertiary hospital in Singapore: a prospective study.
AB  - BACKGROUND: Peptic ulcers due to nonsteroidal anti-inflammatory drug (NSAID) use
      may have contributed to the static prevalence of ulcer disease in Asia. GOAL: We
      aimed to determine the current etiology of peptic ulcer disease in Singapore.
      STUDY: Consecutive patients undergoing esophagogastroduodenoscopy who had not
      been exposed to antibiotics, or antiulcer therapy within the past 6 months, and
      in whom peptic ulcers were found, were prospectively studied. Before endoscopy,
      patients were interviewed regarding the use of NSAID or aspirin. During
      endoscopy, antral biopsies were obtained for urease test and histology. Serum
      thromboxane B2 levels were compared with those of healthy volunteers. RESULTS:
      Peptic ulcers were detected in 600 patients during a 2-year period. The ulcers
      were negative for Helicobacter pylori in 212 patients (35.3%) and these H. pylori
      negative ulcers were related to NSAID use in 68.9% of cases. On the basis of
      serum thromboxane B2 levels, 30.8% of the patients with non-H. pylori non-NSAID
      were considered to have consumed NSAID. CONCLUSIONS: H. pylori negative peptic
      ulcer makes up a significant proportion of peptic ulcer in Singapore. Most of
      these ulcers were related to NSAID use. Serum thromboxane profile suggested
      surreptitious NSAID use in many of the non-H. pylori and apparently non-NSAID
      patients.

PMID- 17016135
TI  - Clinicopathologic features and treatment of residual early cancers after
      endoscopic mucosal resection of the stomach.
AB  - GOALS: We sometimes encounter residual or recurrent cancers after endoscopic
      mucosal resection (EMR) for early gastric cancer. The aim of the present study
      was to clarify the clinicopathologic characteristics of and optimal treatment for
      the residual cancers after EMR. STUDY: Seventy-four patients with early gastric
      cancer were treated with EMR between 1994 and 2004. These patients were divided
      into 2 groups as follows: the curative group (n=59) and the noncurative group
      (n=15). The clinicopathologic data were compared between the 2 groups and the
      outcomes of additional therapy were reviewed. RESULTS: In the noncurative group,
      the tumors were located significantly frequently on the upper or middle third of
      the stomach compared with the curative group (P<0.05). The number of fragments in
      EMR was significantly larger in the noncurative group than in the curative group
      (P<0.05). Fifteen patients required additional treatment because of the residual
      cancer. Nine (75%) of 12 patients requiring surgery underwent laparoscopic
      surgery. Three patients were treated by endoscopic therapy. CONCLUSIONS: EMR with
      a single fragment and with a sufficient margin is useful for the complete
      resection of early gastric cancer. When residual cancer occurs, laparoscopic
      gastrectomy may be a good alternative.

PMID- 17016136
TI  - Should stored serum of patients previously tested for celiac disease serology be
      retested for transglutaminase antibodies?
AB  - INTRODUCTION: Tissue transglutaminase (tTG) antibodies are currently recognized
      as a highly sensitive indicator of celiac disease (CD). Although a high
      concordance rate between tTG antibodies and anti-endomysial antibodies (EMA) has
      been reported up to a third of known CD patients are positive for only one of
      these antibodies. AIM: To determine whether in laboratories in which serum
      samples previously examined for CD serology markers had not been discarded, these
      samples should be tested for tTG antibodies. METHODS: Fifty-eight stored (frozen
      at -70) serum samples of patients previously found to be EMA-negative but
      positive for one or more of the non-EMA markers: antigliadin antibodies (AGA)
      IgA, AGA-IgG, antireticulin antibodies, were tested for anti-tTG antibodies
      (IMMCO Diagnostics). In patients found to be tTG positive, medical charts were
      reviewed and patients or their physicians contacted. RESULTS: Twelve of fifty
      eight (20.7%) samples were found to be anti-tTG positive. These included: group
      A: 3/3 samples previously positive for AGA-IgA, AGA-IgG, and antireticulin
      antibodies. Group B: 3/16 samples positive for AGA-IgA and AGA-IgG. Group C: 3/4
      samples positive for AGA-IgA and group D: 3/35 samples positive for AGA-IgG. Of
      the 12 positive patients, 1 was a 2-year-old boy, 5 were lost to follow up, and 7
      underwent an intestinal biopsy. In 3 of these 7 patients, the biopsy was
      compatible with CD; 2 of these 3 patients were from group A and 1 from group B.
      CONCLUSIONS: In laboratories where stored serum samples are available, EMA
      negative samples previously found to be positive for at least 2 other CD markers
      should be retested for tTG antibodies.

PMID- 17016137
TI  - The search for a common thrombophilic state during the active state of
      inflammatory bowel disease.
AB  - The clinical course of inflammatory bowel disease (IBD) is frequently associated
      with thromboembolic complications. The aim of this study was to investigate
      common thrombophilic markers in Turkish patients with active IBD. Twenty-seven
      consecutive patients with IBD who were followed-up at the Hacettepe University
      Hospital were recruited. All the patients were in the active disease state.
      International normalized ratio, activated partial thromboplastin time, lupus
      anticoagulant, anticardiolipin IgG, IgM antibodies, protein C, protein S,
      antithrombin-III, factor V, and factor II mutation of all the IBD patients and of
      a sex-matched and age-matched control group of non-IBD patients were measured.
      International normalized ratio, activated partial thromboplastin time, protein C,
      protein S, lupus anticoagulant, anticardiolipin IgG and IgM, and Proteins C and S
      mutations were comparable between the 2 groups, but antithrombin-III was
      significantly lower in the IBD group compared with healthy control group
      (P<0.0001). As a conclusion, it is reasonable to assume that there may be a
      subpopulation of the patients with IBD, in whom thrombophilic abnormalities might
      be important for either disease manifestation or for thrombotic complications.
      Those hemostatic abnormalities could be either inherited or secondary to the
      ongoing disease process. Routine screening for the common markers of
      thrombophilia does not seem to be warranted unless simultaneous arterial and
      venous thrombosis, major organ thrombosis, strong family history of
      thrombophilia, unusual and recurrent thrombosis resistant to standard
      anticoagulant therapy are present. Further studies are definitely required to
      clarify these complicated associations.

PMID- 17016138
TI  - Different autonomic responses to experimental pain in IBS patients and healthy
      controls.
AB  - BACKGROUND: Pain perception ratings in irritable bowel syndrome (IBS) patients
      suggest that they present either hypoalgesia or hyperalgesia. However, little is
      known about the physiologic responses these patients present to a somatic painful
      stimulus. GOALS: The main goal of this project was to study autonomic nervous
      system responses and the cardiac response to experimental pain in IBS patients.
      STUDY: This was addressed by exposing 27 women, 14 IBS, and 13 healthy controls
      (HCs), to a cold water (7 degrees C) immersion test of the forefoot for 2
      minutes. Pain perception, galvanic skin responses (GSR), and heart rate (HR) were
      monitored during and after the immersion. RESULTS: For comparable pain
      perception, a significant group difference (P<0.02) in the cardiac response was
      observed during the immersion where the peak rise in HR was much higher for HCs,
      reaching 22%, whereas it only reached 8% for IBS patients. Moreover, HR
      variability analysis demonstrated that IBS and HCs had opposite autonomic cardiac
      reactivity to pain, where IBS had increased parasympathetic/decreased sympathetic
      reactivity. CONCLUSIONS: For comparable pain perception, IBS subject demonstrated
      different autonomic nervous system response to pain, which supports the view of
      autonomic dysregulation in IBS.

PMID- 17016139
TI  - Prospective evaluation of the use and outcome of admission stool guaiac testing:
      the Digital Rectal Examination on Admission to the Medical Service (DREAMS)
      Study.
AB  - BACKGROUND: Although physicians often perform fecal occult blood testing at the
      time of hospital admission, the practice of admission stool guaiac (ASG) testing
      has not been evaluated prospectively. The aim of this study was to determine the
      frequency and outcomes of digital rectal examination (DRE) and ASG testing in
      patients admitted to the hospital. METHODS: We prospectively evaluated 2143
      patients admitted to the medical service at our hospital over a 1-year period. A
      detailed clinical history was obtained, and the proportion of patients who had
      DRE and ASG testing, the frequency of positive tests, and the results of follow
      up testing were determined. RESULTS: A DRE was performed in 1539 of the 2143
      subjects (71.8%), and 1.8% had abnormal findings, 21.8% had a normal examination,
      and the result of ASG testing was the only documented finding in the remaining
      76.4% of patients. ASG testing was performed in 1342 of the 2143 subjects
      (62.6%), and the ASG test was positive in 237 persons (17.7%). However, only 161
      (67.9%) of those with a positive ASG test had further diagnostic testing and a
      colonic source of occult gastrointestinal blood loss was detected in 68 (42.2%)
      of these 161 persons. CONCLUSIONS: Although DRE and ASG testing are commonly
      performed on admission to the hospital, documentation of the findings and follow
      up of positive tests are poor. These findings highlight the need to improve
      physician training on the appropriate use and documentation of the DRE and fecal
      occult blood testing.

PMID- 17016140
TI  - Potential relationship between gastroesophageal reflux disease and atrial
      arrhythmias.
AB  - A potential reduction in symptoms related to atrial fibrillation after treatment
      of gastroesophageal reflux disease symptoms with proton pump inhibitor therapy
      has been previously described. However, illustration of this relationship by
      combined 24-hour pH and ambulatory Holter monitoring has not been performed. We
      report 3 patients with symptoms of both palpitations and reflux who underwent
      simultaneous Holter and 24-hour ambulatory pH monitoring off of antireflux
      therapy. All of the patients reported a reduction in arrhythmia symptoms on
      proton pump inhibitor therapy. The findings from this preliminary series suggest
      a potential relationship between gastroesophageal reflux disease and atrial
      arrhythmias that might improve with antireflux therapy. Patients with
      documentation of both atrial arrhythmias and reflux should have a trial of
      aggressive acid suppressive therapy To further confirm this relationship, larger
      prospective studies are needed to assess whether maximal acid suppression
      improves arrhythmias.

PMID- 17016141
TI  - Acute alcoholic hepatitis.
AB  - Acute alcoholic hepatitis (AAH) is a frequent inflammatory liver disease with
      high short-term mortality rate. In this review, relationships between alcohol
      abuse and the epidemiology and the outcomes of AAH are discussed, as well as AAH
      pathogenesis. The role of endotoxins, tumor necrosis factor alpha, fibroblasts,
      and immune response to altered hepatocyte proteins is discussed. The need of a
      careful prognosis, supported by the use of Maddrey score, by the model for end
      stage liver disease [Mayo end-stage liver disease (MELD)] score or by the Glasgow
      alcoholic hepatitis score, is outlined, as the use of the most effective drugs
      (glucocorticoids and anti-tumor necrosis factor alpha infliximab) is recommended
      only in severe AAH cases. The problems of liver transplant in severe AAH, and the
      need of a 6-month alcohol abstinence before transplant, are discussed, as well as
      the need of a careful psychologic assessment before the transplant.

PMID- 17016142
TI  - Novel concepts in hepatocellular carcinoma: from molecular research to clinical
      practice.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in the
      world, burdened by a constantly increasing frequency. Therapy is currently
      restricted to invasive techniques but prognosis and survival are still
      unsatisfactory, mainly because of HCC recurrence and metastasis diffusion. This
      review will focus on the problem of tumor recurrence and/or metastasis, pointing
      out the role of the tissue microenvironment in affecting HCC behavior; new
      experimental findings will also be discussed in the light of their implications
      in medical care. Finally, new therapeutic approaches will be considered, paying
      particular attention to the tissue microenvironment as a potential target. In
      conclusion, this review will attempt to stimulate debate on translational
      research into HCC biology, in the field of clinical applications.

PMID- 17016143
TI  - Autoimmune pancreatitis in young patients.
AB  - GOALS: To examine whether there is a difference in the autoimmune pancreatitis
      (AIP) seen in young and elderly patients. BACKGROUND: AIP has a preponderance for
      elderly males, although the reason is unknown. STUDY: A total of 64 patients with
      AIP were divided into a young (<40 y old) group and a middle-aged or elderly
      group (> or =40 y old) according to the age at diagnosis. The clinical findings
      of each group were compared. RESULTS: The young group consisted of 6 patients (3
      men, 3 women) with a mean age of 33.0 (range, 28 to 37) years. In the middle-aged
      or elderly group, there were 58 patients with a mean age of 66.4 (range, 46 to
      83) years; males predominated (79%). Abdominal pain as the presenting symptom was
      significantly more frequent in the young group than in the middle-aged or elderly
      group (100% vs. 43%, P<0.05). Obstructive jaundice was detected in only 17% (1/6)
      of patients in the young group compared with 59% (34/58) of patients in the
      middle-aged or elderly group. Serum amylase elevations were detected more
      frequently in the young group than in the middle-aged or elderly group (83% vs.
      40%, P<0.05). One young patient also had ulcerative colitis. CONCLUSIONS:
      Although rare in Japan, young patients with AIP show different clinical features
      from middle-aged or elderly patients with AIP; young patients are more likely to
      have abdominal pain and serum amylase elevations.

PMID- 17016144
TI  - Does secretin-stimulated MRCP predict exocrine pancreatic insufficiency?: A
      comparison with noninvasive exocrine pancreatic function tests.
AB  - BACKGROUND: Data on magnetic resonance cholangiopancreatography with secretin
      stimulation (S-MRCP) for the assessment of exocrine pancreatic insufficiency
      (EPI) are limited. We compared pancreatic function tests with the findings of S
      MRCP in patients with chronic pancreatitis (CP) and disease controls. METHODS: S
      MRCP was performed in 23 patients (18 CP, 5 disease controls). MRCP images were
      analyzed for secretin-induced duodenal liquid filling (0=no filling; 1=duodenal
      bulb; 2=up to lower flexure; 3=beyond lower flexure). EPI was evaluated by fecal
      elastase, fecal fat concentration, and a 13C mixed chain triglyceride breath
      test. Clinically relevant EPI was stated if 2 of 3 tests were pathologic.
      RESULTS: EPI was diagnosed in 10 of 18 patients with CP. Patients without EPI
      showed either grade 2 (n=4) or grade 3 (n=9) duodenal filling, whereas only 1/10
      patients with EPI showed grade 3 duodenal filling. Sensitivity and specificity of
      S-MRCP for the diagnosis of EPI were 69% and 90%, respectively. CONCLUSIONS:
      Assessment of duodenal filling should be performed in patients who undergo S-MRCP
      for the evaluation of pancreatic morphology. However, minor degrees of duodenal
      filling are equivocal and require further diagnostic evaluation.

PMID- 17016145
TI  - Management of intraductal papillary-mucinous neoplasm of the pancreas: treatment
      strategy based on morphologic classification.
AB  - GOALS: The aim of this study was to examine and clarify the preoperative markers
      that are useful for differentiating between benign and malignant lesions of
      intraductal papillary-mucinous neoplasms (IPMN) of the pancreas, grouped
      according to morphologic classification. BACKGROUND: There are various stages of
      pathology in IPMN, ranging from benign to malignant lesions. Although the
      determination of appropriate treatment guidelines to deal with IPMN is a critical
      issue, no such guidelines have been established. PATIENTS AND METHODS: One
      hundred twenty cases of IPMN were classified morphologically into either main or
      branch duct types. We compared the morphologic classification with
      histopathologic diagnosis using indicators of malignancy detected by imaging such
      as main duct diameter, the number and diameter of cysts, and the presence or
      absence of mural nodules. We also examined the usefulness of pancreatic juice
      cytology and measurement of telomerase activity as indicators of malignancy.
      Finally, we performed a survival analysis on the basis of morphologic
      classification to determine prognosis of IPMN. RESULTS: Whereas a high incidence
      (64%) of malignant lesions was seen in main duct type IPMN, benign lesions were
      dominant (80.5%) in branch duct type IPMN. Survival analysis showed that the
      prognosis was significantly worse in main duct type than in branch duct type
      IPMN. The lesions were aggravated in all patients with main duct type who did not
      undergo resection, resulting in death due to progression of the pancreatic
      lesion. The incidence of mural nodules was a useful indicator in main duct type,
      whereas main duct diameter and incidence of mural nodules were useful indicators
      in branch duct type. Although pancreatic juice cytology showed a high accuracy
      rate with low sensitivity for determining malignancy, measurement of telomerase
      activity in this juice was very effective for differentiating between benign and
      malignant lesions. CONCLUSIONS: The incidence of malignant lesions was extremely
      high in main duct type IPMN, indicating that surgery is required in all these
      patients. However, to determine whether surgery is indicated in branch duct type
      IPMN it is necessary to obtain an appropriate image diagnosis focusing on main
      duct diameter and mural nodules and also to carry out cytology and measurement of
      telomerase activity in samples of pancreatic juice.

PMID- 17016146
TI  - Thyrotoxic hypokalemic periodic paralysis as the first manifestation of
      interferon-alpha-induced Graves disease.

PMID- 17016147
TI  - Widespread occlusive vascular disease in a Crohn's disease patient with profound
      thrombocytosis.

PMID- 17016148
TI  - Initial and serial evoked potentials in cerebrovascular critical care patients.
AB  - Results of somatosensory evoked potential (SEP) and brainstem auditory evoked
      potential (BAEP) examinations performed early in the clinical course of patients
      with acute cerebrovascular disease correlate statistically significantly with
      outcome regardless of type and localization of the primary lesion. The prognostic
      value of serial examinations of SEP and BAEP has not been studied yet. The
      authors examined a group of 215 patients suffering from acute stroke requiring
      neurocritical care composed of 75 supratentorial and 36 infratentorial ischemic
      strokes, 58 supratentorial and 18 infratentorial hemorrhages, and 28 aneurysmatic
      subarachnoid hemorrhages prospectively using spinal and cortical SEP and BAEP
      according to routine procedures on admission as well as after 1 and 2 weeks. The
      findings were correlated to outcome at 4 weeks. Statistical assessment was
      performed using standard methods of contingency analysis. In all groups, SEP
      findings were significantly correlated with outcome at initial and all subsequent
      examinations, similar correlations were also found for BAEP. However, after
      partialling out the prognostic information gained from the initial examination of
      SEP and BAEP, the follow-up examinations rendered only a marginal increase in
      prognostic information. Therefore, the initial examination of evoked potentials
      supplies valuable prognostic information, however, serial examinations of evoked
      potentials during the first weeks of disease improve the prognostic information
      only marginally.

PMID- 17016149
TI  - EEG coherence obtained from an auditory oddball task increases with age.
AB  - Changes in coherence with aging during cognitive tasks have, until now, not been
      investigated. However, several fMRI and positron emission tomography studies of
      cognitive tasks have found increased bilateral activity in elderly subjects.
      Changes in coherence with aging during a cognitive task were investigated to see
      if EEG coherence was present in older adults. An auditory oddball task, which is
      a widely used test for cognitive function, was used. Eleven young adults (27.8 +/
      4.8 years, six females) and 10 older adults (61.3 +/- 4.6 years, six females)
      were studied, and both interhemispheric and long- and short-range
      intrahemispheric coherence were considered. Higher interhemispheric coherence was
      found in the older subjects in the delta band. Short intrahemispheric coherence
      was also increased in the theta, delta, and alpha bands. Higher coherence,
      although not significantly different, was also found for all other coherence
      types and bands, except for long intrahemispheric coherence in the low gamma
      band. The results presented here provide the first evidence that aging is
      associated with increased EEG coherence during a relatively easy cognitive task.

PMID- 17016150
TI  - Localizing sites of activation in primary visual cortex using visual-evoked
      potentials and functional magnetic resonance imaging.
AB  - This study compared retinotopic map identification in primary visual cortex (V1)
      using: (i) functional magnetic resonance imaging (fMRI) and (ii) visual evoked
      potentials (VEPs) coupled with dipole source localization (DSL). A multielectrode
      array was used to record VEPs while subjects viewed a flickering dartboard
      pattern modulated by a 16-bit m-sequence. The stimulus preferentially activates
      V1. Using a common time function DSL algorithm, the primary source of each
      stimulus patch was found independent of the fMRI. The VEP/DSL and fMRI
      localization data for each subject were aligned by a rigid translation and
      rotation. The average distance between VEP and corresponding fMRI sources was
      10.8 mm +/- 3.8 mm. To assess the significance of the results, fMRI and DSL
      solutions were scrambled so the comparisons were no longer for corresponding
      patches. The average distance between the noncorresponding data sets was 17.2 mm
      for 50 million scrambles. The probability of the scrambled data yielding a better
      fit than the real data was p < 10(-7). The combination of multielectrode
      recording, multiinput visual stimulation and common time function DSL analysis
      can provide a detailed retinotopic map of visual cortex that has high
      correspondence with independent fMRI localization analysis on the same subject.

PMID- 17016151
TI  - Motion-onset and pattern-reversal visual evoked potentials in diagnostics of
      neuroborreliosis.
AB  - Neuroborreliosis is a form of borreliosis that affects the central and/or
      peripheral nervous system. Although it can mimic neurologic and ophthalmologic
      disorders such as multiple sclerosis and optic neuritis, visual evoked potential
      (VEP) examination is usually not used in neuroborreliosis diagnostics. Combined
      VEP testing (pattern-reversal VEPs and VEPs produced in response to linear and
      radial motion) was performed in 81 patients with neuroborreliosis verified by
      laboratory results (positive polymerase chain reaction or intrathecal antibodies
      production). Thirty-four patients reported diplopia or blurred vision related to
      borreliosis. In 33 (40%) patients the VEPs were delayed: motion-onset VEPs were
      pathologic in 22 (27%) patients, reversal VEPs in 5 (6%) patients, and both VEP
      types in 6 (7%) patients. The findings suggest that VEP testing (especially the
      motion-onset VEP testing) can confirm CNS involvement. Much higher sensitivity of
      motion-onset VEPs in comparison with reversal VEPs can result from rather
      selective (earlier) involvement of the magnocellular system or the dorsal stream
      of the visual pathway.

PMID- 17016152
TI  - Sensory gating deficit assessed by P50/Pb middle latency event related potential
      in Alzheimer's disease.
AB  - Sensory gating is defined as the brain's ability to inhibit repetitive and
      irrelevant incoming sensory stimuli and is supposed to be related to cholinergic
      transmission. Indeed, Alzheimer's disease (AD) is characterized by a cholinergic
      deficit that is believed to be involved in cerebral cortex hyperexcitability and
      short latency afferent inhibition deficit. Therefore, a sensory gating deficit
      may be supposed present in AD within the frame of cortex hyperexcitability and
      loss of cortex modulation of sensory inputs. The authors investigated whether a
      sensory gating deficit may be present in AD and whether this deficit may be
      related to the presence of neuropsychiatric symptoms (NPS) and reversed by
      donepezil treatment. Sensory gating was evaluated using a paired-stimulus
      auditory P50 event-related potential paradigm. Eighteen drug-naive probable AD
      patients (mean age 76.1 years; SD 5.6 years; 13 females and 5 males) and 15
      healthy elderly controls (mean age 74.2 years; SD 5.4 years; 10 females and 5
      males) were recruited. Sensory gating was evaluated in AD patients before
      starting therapy and after 1 and 3 months of donepezil treatment. Auditory P50
      sensory gating was impaired in AD patients but no correlation was found between
      gating deficit and NPS. Moreover, AD patients displayed increased P50 amplitude
      when compared with healthy elderly subjects. Donepezil treatment did not improve
      P50 sensory gating in AD patients but decreased P50 amplitude. Patients with AD
      displayed an augmented P50 amplitude, in accordance with previous studies,
      suggesting increased cortex excitability. Donepezil does not affect P50 sensory
      gating but reduces P50 amplitude. Donepezil may induce P50 amplitude reduction by
      means of enhanced dopamine release. Indeed, it has been demonstrated that
      donepezil induces dopamine release "in vitro." The findings suggest that AD
      patients have a sensory gating impairment but the link with both NPS and the
      cholinergic deficit is doubtful.

PMID- 17016153
TI  - Effects of general anesthesia on high-frequency oscillations in somatosensory
      evoked potentials.
AB  - To determine the characteristics of high-frequency oscillations (HFOs) of
      cortical somatosensory evoked potentials (SEPs), the effect of general anesthesia
      on HFOs and low-frequency primary cortical responses was studied. The authors
      recorded SEPs elicited by median nerve stimulation directly from human brains of
      seven patients who underwent implantation of subdural electrodes before surgical
      treatment of intractable epilepsy. Recordings were made before and during general
      anesthesia. Changes in the number of HFOs and amplitude ratios of HFOs/primary
      cortical responses were analyzed. Under general anesthesia, the number of HFO
      peaks and the amplitude ratios were significantly decreased. General anesthesia
      induced remarkably decreased HFO activities when compared to low-frequency SEPs,
      suggesting that each of those originated from different generators. Possible
      relations between gamma-amino-butyric acid (GABA)ergic inhibitory interneurons
      and HFOs are discussed.

PMID- 17016154
TI  - Visual-evoked potentials to onset of chromatic red-green and blue-yellow gratings
      in Parkinson's disease never treated with L-dopa.
AB  - The differential dysfunction of chromatic and achromatic visual pathways in early
      Parkinson's disease (PD) was evaluated by means of visual-evoked potentials
      (VEPs) recorded in 12 patients (mean age 60.1 +/- 8.3 years; range 46 to 74
      years) in the early stages of PD and not yet undergoing treatment with L-dopa,
      and in 12 age-matched controls. Visual stimuli were full-field (14 deg)
      equiluminant red-green (R-G), blue-yellow (B-Y), and black-white (B-W) sinusoidal
      gratings of two cycles per degree, presented in onset (300 milliseconds)--offset
      (700 milliseconds) mode, at two contrast (K) levels (90% and 25%). The VEP mean
      latencies were significantly more delayed in PD patients than in controls for
      chromatic than for luminance stimuli, in particular for B-Y stimuli of low
      contrast (K90%: B-W = 6.6 milliseconds, R-G = 3.34 milliseconds, B-Y = 15.48
      milliseconds; K25%: B-W = 7.8 milliseconds, R-G = 14.8 milliseconds, B-Y = 28.9).
      Latencies of chromatic VEPs were more variable that achromatic VEP latencies in
      both normal subjects and PD patients. Therefore, the frequency of latency
      abnormalities (within 30%) was not significantly different for the three visual
      stimuli. Our results show that, in addition to achromatic VEPs, chromatic VEPs
      are impaired in early PD patients not yet undergoing L-dopa therapy, indicating
      an acquired color deficiency in these patients. The greater delay for the B-Y
      VEPs suggests a higher vulnerability of visual blue-cone pathway in the early
      stages of the disease. However, the overall sensitivity of chromatic VEPs in
      detecting early visual impairment in PD is comparable with that of achromatic
      VEPs.

PMID- 17016155
TI  - Focal epileptiform spikes in conjuction with K-complexes.
AB  - Dyshormia or epileptiform spikes occurring within K-complexes have been described
      in patients with generalized epilepsy, with one study reporting that generalized
      spikes occurred frequently in association with K-complexes. We report the rate of
      focal epileptiform spikes occurring within K-complexes in localization-related
      epilepsy. Presurgical or diagnostic long-term video-EEG results of 40 consecutive
      patients with epilepsy (13 patients with right temporal lobe epilepsy, 20
      patients with left temporal lobe epilepsy, and 7 patients with frontal lobe
      epilepsy) were reviewed. Sleep samples were reviewed and the numbers of K
      complexes, spikes, and spikes within K-complexes were recorded. The comparison
      group consisted of 40 consecutive patients with nonepileptic events who were
      monitored with long-term video EEG. Focal epileptiform spikes occurring within K
      complexes occurred in 2 of 13 (15%) patients with right temporal lobe patients, 6
      of 20 (30%) patients with left temporal lobe, and 3 of 7 (42%) patients with
      extratemporal lobe epilepsy. In most patients, spikes occurring during K
      complexes were rare. We identified spikes occurring during K-complexes in
      patients with localization-related epilepsy. The sharply contoured components of
      K-complexes or associated sleep spindles may obscure focal spikes within K
      complexes. Nevertheless, K-complexes may be associated with focal epileptiform
      discharges.

PMID- 17016156
TI  - A meta-analysis of quantitative EEG power associated with attention-deficit
      hyperactivity disorder.
AB  - A meta-analysis was performed on quantitative EEG (QEEG) studies that evaluated
      attention-deficit hyperactivity disorder (ADHD) using the criteria of the DSM-IV
      (Diagnostic and Statistical Manual of Mental Disorders, 4th edition). The nine
      eligible studies (N = 1498) observed QEEG traits of a theta power increase and a
      beta power decrease, summarized in the theta/beta ratio with a pooled effect size
      of 3.08 (95% confidence interval, 2.90, 3.26) for ADHD versus controls (normal
      children, adolescents, and adults). By statistical extrapolation, an effect size
      of 3.08 predicts a sensitivity and specificity of 94%, which is similar to
      previous results 86% to 90% sensitivity and 94% to 98% specificity. It is
      important to note that the controlled group studies were often with
      retrospectively set limits, and that in practice the sensitivity and specificity
      results would likely be more modest. The literature search also uncovered 32 pre
      DSM-IV studies of ADHD and EEG power, and 29 of the 32 studies demonstrated
      results consistent with the meta-analysis. The meta-analytic results are also
      supported by the observation that the theta/beta ratio trait follows age-related
      changes in ADHD symptom presentation (Pearson correlation coefficient, 0.996, P =
      0.004). In conclusion, this meta-analysis supports that a theta/beta ratio
      increase is a commonly observed trait in ADHD relative to normal controls.
      Because it is known that the theta/beta ratio trait may arise with other
      conditions, a prospective study covering differential diagnosis would be required
      to determine generalizability to clinical applications. Standardization of the
      QEEG technique is also needed, specifically with control of mental state,
      drowsiness, and medication.

PMID- 17016157
TI  - Quantitative EEG findings in different stages of Alzheimer's disease.
AB  - Although quantitative EEG (q-EEG) has been used in Alzheimer's disease (AD), q
      EEG changes in AD are complex because of the progressive nature of this disease.
      The topographical spectral power and occipital peak frequency (OPF) were compared
      among elderly controls, patients with mild cognitive impairment (MCI), and
      patients with four stages of AD. In AD patients, except those with a Clinical
      Dementia Rating Scale (CDR) score of 0.5, OPF was lower than that of elderly
      controls. Compared with elderly controls, the left anterior alpha spectral power
      was reduced in CDR 0.5; both posterior theta spectral powers were increased and
      all alpha spectral powers were reduced in CDR 1; all alpha and beta spectral
      powers were reduced and theta spectral power was increased in CDR 2; and all
      alpha and beta spectral powers were reduced and all delta and theta spectral
      powers were increased in CDR 3. Patients with MCI exhibited a reduction in both
      centrotemporal, posterior delta and left anterior, centrotemporal theta fields.
      The Mini-Mental State Examination (MMSE) score was related to left OPF, right
      posterior delta and left anterior theta spectral power, in that order. This study
      suggests that q-EEG in MCI shows nonoverlapping features between controls and AD
      patients, and AD patients show dynamic changes as the disease progresses.
      Finally, the left OPF is the parameter most significantly correlated with MMSE
      score.

PMID- 17016158
TI  - Focality assessment in transcranial magnetic stimulation with double and cone
      coils.
AB  - To evaluate the performance with respect to selectivity of the effect of the
      wings bending in the cone coil relative to the double coil in transcranial
      magnetic stimulation. The focal area and the width vector of the central lobe of
      the induced electrical field distributed along an elliptic surface approximating
      the cortex were computed for four coil models. The models represented the real
      coils, the double B70 and the cone B80 Medtronic, and their corresponding
      simulated flat coils (B70flat and B80flat). A response function was evaluated in
      10 subjects for distal and proximal muscles of the upper limb by stimulation of
      the motor cortex along a line approximating the central sulcus. The width of the
      response function, at the level of the center of gravity, provided a quantitative
      measure for coil focality. The focal area for B70, B70flat, B80, and B80flat
      calculated from the model was 31.4, 32.2, 94.4, and 50.6 cm2, respectively. The
      width of the central lobe along the stimulation line was: 36.2, 37, 46, and 48.6
      mm, respectively. Mean values of focality measure obtained experimentally were in
      distal muscles, 5.06 RPU (relative position units) for B70 and 5.99 RPU for B80;
      in proximal muscles, 4.11 RPU for B70 and 5.13 RPU for B80, with a mean RPU value
      of 11.13 mm. The difference, a 19% focality measure increase in B80 relative to
      B70 in distal muscles, was statistically significant (P < 0.001). The focality
      was demonstrated to be highest for the double coil. The width of the central lobe
      of the induced electrical field distribution is well reflected in the width of
      the response function. The increase in B80 is mainly due to wing geometry and
      relative placement of wings and is not due to the wing bending. The width of the
      central lobe characterizes the spread of the induced current below the wing
      junction, and it is a better focality estimator than the focal area for cone
      coils.

PMID- 17016159
TI  - Transcranial magnetic stimulation in motor conversion disorder: a short case
      series.
AB  - The neurophysiologic mechanisms involved in nonorganic paralysis are unclear.
      Because there is no established standard therapy, the authors investigated the
      effect of repetitive transcranial magnetic stimulation (rTMS) in four patients
      with nonorganic limb paralysis. Within the framework of a treatment trial, the
      patients were treated over a period of 5-12 weeks with rTMS applied to the
      contralateral motor cortex. Stimulation frequency was 15 Hz, train length 2
      seconds, intertrain interval 4 seconds; daily total number of stimuli 4000. In
      one patient, motor function was completely restored; two patients experienced a
      marked improvement correlating with rTMS treatment. By contrast, one patient who
      had been diagnosed as a malingerer did not improve. Apart from possible favorable
      psychological factors that could partly explain the rTMS-associated effects, high
      frequency rTMS might have enhanced or substituted an insufficient input to the
      motor cortex from failing frontal executive areas, and thereby opened the way to
      a learning process that lead to the reacquisition of limb use. rTMS may have a
      therapeutic effect in motor conversion disorder and may help elucidate
      neurophysiologic aspects of this condition. The potential benefit of rTMS in
      motor conversion disorder should be evaluated in larger, controlled samples.

PMID- 17016160
TI  - Acetylcholinesterase inhibition in patients with orthostatic intolerance.
AB  - The efficacy of current therapeutic measures in orthostatic intolerance (OI)
      varies among patients and is oftentimes unsatisfactory. New approaches to
      alleviate symptoms of OI are therefore clearly needed. Recent reports have
      demonstrated that acetylcholinesterase inhibition is effective in the treatment
      of orthostatic hypotension with the presumed mechanism of enhancing sympathetic
      ganglionic transmission. Based on the hypothesis that acetylcholinesterase
      inhibition, by improving the safety factor of cholinergic transmission, will
      result in enhanced vascular adrenergic tone and a vagal shift in cardiac
      sympathovagal balance, we evaluated the role of acetylcholinesterase inhibition
      in the treatment of patients with OI. We monitored heart rate (HR), blood
      pressure, and indexes for cardiac output, end-diastolic volume, and systemic
      resistance continuously in 18 patients with OI during supine rest and during 5
      minutes of 70 degrees head-up tilt before and 1 hour after oral administration of
      60 mg pyridostigmine. Plasma catecholamines and baroreflex sensitivity were
      determined for the supine and upright position before and after medication.
      Patients scored orthostatic symptoms for both tilt studies. The excessive HR
      response to orthostatic stress was significantly blunted after pyridostigmine
      administration. HR was significantly lower in the supine and more so in the
      upright position. Baroreflex sensitivity in the upright position was
      significantly higher after pyridostigmine. Norepinephrine was increased in both
      supine and upright position. These changes were associated with significant
      improvement of orthostatic symptoms. We conclude that pyridostigmine improves
      orthostatic tolerance in patients with OI. Our findings support the suggested
      mechanisms of enhanced sympathetic ganglionic neurotransmission and a vagal shift
      in cardiac sympathovagal balance. Acetylcholinesterase inhibition could be a new
      useful concept in the treatment of OI.

PMID- 17016161
TI  - Proposal of a new criterion for electrodiagnosis of meralgia paresthetica by
      evoked potentials.
AB  - We examined 19 subjects with meralgia paresthetica (bilateral in three cases),
      recording bilateral somatosensory-evoked potentials (SSEPs) after stimulation of
      the tibial posterior nerve (TPN) and cutaneous stimulation in the region of the
      lateral femoral cutaneous nerve (LFCN). We calculated the difference between TPN
      SSEPs and LFCN SSEPs cortical potentials, identifying a temporal parameter that
      we termed D(SEP). We defined D(SEP) normal values in a control group. D(SEP)
      evaluation showed good sensitivity and specificity (85.7% and 82.4%,
      respectively; accuracy, 83.3%) in discriminating affected limbs from unaffected.
      The main advantage of this method is to disengage from the necessity of
      contralateral comparison of LFCN recordings, joined with a reduction of
      interindividual variability of LFCN SSEPs amplitude and latency that often causes
      a lower sensitivity of other methods. As an interesting consideration, D(SEP)
      evaluation appears to mark out a possible subclinical involvement of LFCN in the
      asymptomatic side of patients with meralgia paresthetica.

PMID- 17016162
TI  - Survey says: care, communication enhanced by IT. Nurses report ups and downs of
      current systems.

PMID- 17016163
TI  - How does technology drive safety? Travel to a patient-centered culture.

PMID- 17016164
TI  - Raise your smart pump IQ. Gain further perspectives on this key medication safety
      tool.

PMID- 17016165
TI  - Making smarter staffing decisions.

PMID- 17016166
TI  - Rural hospitals can hit the bull's-eye, too. IT connectivity is making its mark.

PMID- 17016167
TI  - The management of patients on anticoagulants prior to cutaneous surgery: case
      report of a thromboembolic complication, review of the literature, and evidence
      based recommendations.

PMID- 17016168
TI  - Treatment of lower extremity lymphedema with suction-assisted lipectomy.

PMID- 17016169
TI  - Current options in head and neck reconstruction.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand current trends in the treatment of head and neck cancer. 2.
      Discuss the challenges of reconstructing head and neck defects 3. Understand the
      different reconstructive options available for specific anatomical regions of the
      head and neck. BACKGROUND: Reconstructive surgery of the head and neck is both
      technically challenging and rewarding. In the past 20 years, significant advances
      in this field have improved surgical outcomes and patient function. The
      development and subsequent refinement of microvascular techniques, in particular,
      have been a major reason for this progression. METHODS: In this article, the
      authors review the current options available in head and neck reconstruction.
      Because a large number of major craniocervicofacial defects result from oncologic
      resection, the authors have focused their review on this particular subject. By
      dividing their discussion into different anatomical sites, the authors hope to
      cover all major aspects of this broad topic. RESULTS: Free tissue transfer has
      revolutionized head and neck reconstruction. The most widely used free flaps
      include the fibula, radial forearm, anterolateral thigh, and rectus abdominis.
      Restoration of both form and function is the ultimate goal. CONCLUSIONS: Although
      defects of the head and neck region present a challenge, successful cosmetic and
      functional results have been achieved with both local and free tissue flaps. The
      flexibility of free tissue transfer, however, has dominated this area and
      continues to be the method of choice for reconstruction of sizable defects.

PMID- 17016170
TI  - Comparison of local recurrence and distant metastases between breast cancer
      patients after postmastectomy radiotherapy with and without immediate TRAM flap
      reconstruction.
AB  - BACKGROUND: The purpose of this study was to compare the local recurrence and
      distant metastasis of postmastectomy radiotherapy for breast cancer patients with
      and without immediate transverse rectus abdominis musculocutaneous (TRAM) flap
      reconstruction. METHODS: Between March of 1997 and October of 2001, 191 breast
      cancer patients received postmastectomy radiotherapy: 82 patients had TRAM flap
      reconstruction (TRAM flap group) and 109 patients did not (non-TRAM flap group).
      The mean radiation dose to the chest wall or entire TRAM flap, axillary area, and
      lower neck was 50 Gy (range, 48 to 54 Gy). The median follow-up period was 40
      months. RESULTS: The percentages of chest wall recurrence were 3.7 percent (three
      of 82) in the TRAM flap group and 1.8 percent (two of 109) in the non-TRAM flap
      group (p = 0.653). The percentages of distant metastases were 12.2 percent (10 of
      82) in the TRAM group and 15.6 percent (17 of 109) for the non-TRAM group (p =
      0.67). The percentages of acute radiation dermatitis according to Radiation
      Therapy Oncology Group scoring criteria (TRAM flap group versus non-TRAM flap
      group) were as follows: grade I, 74 of 82 (90 percent) versus 93 of 109 (85
      percent); grade II, seven of 82 (9 percent) versus 13 of 109 (12 percent); grade
      III, one of 82 (1 percent) versus three of 109 (3 percent) (p = 0.558). In the
      TRAM flap group, the increased percentage of fat necrosis was 8 percent. No flap
      loss was detected. CONCLUSIONS: There were no significant differences in the
      incidences of complication, locoregional recurrence, and distant metastasis
      between the TRAM flap and non-TRAM flap patients. The authors' results suggest
      that immediate TRAM flap reconstruction can be considered a feasible treatment
      for breast cancer patients requiring postmastectomy radiotherapy.

PMID- 17016172
TI  - Impact of sentinel lymph node biopsy on the evolution of breast reconstruction.
AB  - BACKGROUND: Although sentinel lymph node biopsy is rapidly replacing complete
      axillary lymph node dissection for lymph node staging in women with clinically
      node-negative breast cancer, it is unclear what impact the transition to sentinel
      lymph node biopsy will have on the practice of breast reconstruction. METHODS: To
      determine the effect of the transition from complete axillary lymph node
      dissection to sentinel lymph node biopsy on their practice of breast
      reconstruction, the authors reviewed the records of 717 patients with breast
      cancer who underwent sentinel lymph node biopsy and 1887 breast reconstructions
      487 were performed in patients who also underwent sentinel lymph node biopsy at
      The University of Texas M. D. Anderson Cancer Center between 1998 and 2003.
      RESULTS: Before 1999, sentinel lymph node biopsy was performed infrequently.
      Between 1999 and 2003, the number of sentinel lymph node biopsy procedures
      performed per year increased almost 50-fold. Concurrent with this increase in the
      use of sentinel lymph node biopsy, there was a corresponding increase in the
      proportion of breast reconstruction procedures performed in patients who had also
      undergone sentinel lymph node biopsy (13 percent per year, p = 0.0001). In 2003,
      54 percent of all breast reconstructions were performed in patients who had
      sentinel lymph node biopsy. In 2000, 1 year after the use of sentinel lymph node
      biopsy began to increase, the choice of recipient vessels for free transverse
      rectus abdominis myocutaneous (TRAM) flap breast reconstruction began to change.
      Between 2001 and 2002, the internal mammary vessels replaced the thoracodorsal
      vessels as the preferred recipient vessels for TRAM flap reconstruction (p <
      0.0001). Over the study period, the authors noted a decrease in the percentage of
      free TRAM flap procedures requiring revision, more frequent use of contralateral
      implant-based augmentation to achieve symmetry, an increase in the percentage of
      patients desiring a second attempt at reconstruction after loss of a TRAM flap,
      and a decrease in the percentage of patients being referred for physical therapy
      or treatment of lymphedema after free TRAM flap reconstruction. CONCLUSIONS: The
      transition from axillary lymph node dissection to sentinel lymph node biopsy has
      resulted in a change in breast reconstruction practices. The increased use of the
      internal mammary vessels reflects the decreased dissection of axillary tissue to
      expose the thoracodorsal vessels with sentinel lymph node biopsy in addition to
      concern that a subsequent axillary surgery to remove additional axillary nodes
      might injure the thoracodorsal vessels should they be used in breast
      reconstruction. Awareness of the decreased morbidity associated with sentinel
      lymph node biopsy has led patients to expect less morbidity and better aesthetic
      outcomes from TRAM flap reconstruction.

PMID- 17016173
TI  - Complications after microvascular breast reconstruction: experience with 1195
      flaps.
AB  - BACKGROUND: Reconstruction is an important adjunct to breast cancer management.
      This study evaluated the frequency of major and minor complications in the
      largest reported series of consecutive mastectomy patients treated with free
      tissue transfer for breast reconstruction. METHODS: All patients treated with
      microvascular breast reconstruction at the University of California, Los Angeles,
      Medical Center over an 11-year period were identified using a retrospective
      analysis. Frequency of complications was assessed. RESULTS: A total of 1195
      breast reconstructions were performed in 952 patients. Transverse rectus
      abdominis musculocutaneous flaps were used in most cases (81.8 percent), whereas
      the superior gluteal musculocutaneous flap (10.1 percent) and other free flaps
      were used in the remaining patients. The overall complication rate was 27.9
      percent and consisted primarily of minor complications (21.7 percent). Major
      complications were noted in 7.7 percent, including six total flap losses (0.5
      percent). Obesity was a major predictor of complications. Smoking was not
      associated with increased rates of overall or microsurgical complications.
      Neoadjuvant chemotherapy was also an independent predictor of complications and
      was associated with wound-healing problems and fat necrosis. Prior abdominal
      surgery in transverse rectus abdominis musculocutaneous flap patients increased
      the risk of partial flap loss, fat necrosis, and donor-site complications.
      CONCLUSIONS: Microsurgical breast reconstruction is a safe and highly effective
      technique. Complications tend to be minor and do not affect postreconstruction
      adjuvant therapy. Obesity is a major predictor of flap and donor-site
      complications, and these patients should be appropriately counseled. Similarly,
      neoadjuvant preoperative chemotherapy and prior abdominal surgery increase the
      rates of minor complications.

PMID- 17016175
TI  - Tissue engineering of injectable muscle: three-dimensional myoblast-fibrin
      injection in the syngeneic rat animal model.
AB  - BACKGROUND: Surgical treatment of skeletal muscle loss resulting from trauma,
      tumor ablation, or inborn tissue defects is hampered by the scarcity of
      functional substitute tissue. By using techniques of tissue engineering,
      reconstitution of skeletal muscle defects might become a more viable option.
      However, it is necessary to develop an adequate, practical method for delivering
      myoblasts within a three-dimensional scaffold in vivo. The aim of this study was
      to create and evaluate a novel method for the transfer of myoblasts with
      clinically approved components within a three-dimensional matrix. METHODS: The
      authors injected expanded primary male myoblasts into muscle defects in female
      syngeneic rats using a two-way syringe (Duploject) within a three-dimensional
      fibrin matrix. Detection and evaluation were performed using Y chromosome in situ
      hybridization, antidesmin immunostaining, and hematoxylin and eosin staining. To
      identify possible differences by means of integration, the injected myoblasts
      were compared with 7 days of precultivated constructs. RESULTS: Injected
      myoblasts showed increasing integration into host muscle fibers in a time
      dependent manner, exclusively at the injection site. Antidesmin staining revealed
      a conserved myogenic phenotype of transplanted cells. The fibrin matrix resolved
      over a period of 12 weeks, with no indication of an inflammatory reaction. No
      significant difference in the number of detected Y chromosome-positive nuclei was
      found between the two transplantation groups. CONCLUSIONS: The presented
      technique of myoblast-fibrin injection indicates a clinical potential for
      reconstruction of skeletal muscle defects in vivo using a ready-to-use device in
      combination with tissue-engineering methods.

PMID- 17016177
TI  - Early-gestation fetal scarless wounds have less lysyl oxidase expression.
AB  - BACKGROUND: Lysyl oxidase cross-links collagen and elastin. Because cross-linking
      likely influences collagen architecture, the authors compared lysyl oxidase
      expression during scarless and scarring fetal dermal wound repair. METHODS:
      Excisional dermal wounds were made on E17 (gestational day 16.5) and E19
      (gestational day 18.5) mouse fetuses. Skin and wound RNA was collected at 8, 12,
      and 24 hours. Quantitative real-time polymerase chain reaction was performed for
      lysyl oxidase. The effect of transforming growth factor (TGF)-beta1 on lysyl
      oxidase expression in fetal fibroblasts was tested. Confluent primary fetal and
      postnatal fibroblast cultures were stimulated with TGF-beta1 for 24 hours, and
      lysyl oxidase expression was quantitated by performing real-time polymerase chain
      reaction. Lysyl oxidase expression was also quantitated in unwounded fetal skin
      to determine its expression profile during development. RESULTS: E17 and E19
      fetal skin had approximately 2-fold greater lysyl oxidase expression than
      postnatal skin (p < 0.01), and fetal fibroblasts had greater baseline lysyl
      oxidase expression than postnatal fibroblasts. After TGF-beta1 stimulation, fetal
      and postnatal fibroblasts responded with increases in lysyl oxidase expression.
      In E17 early-gestation scarless fetal wounds, lysyl oxidase had small increases
      (<1.5-fold) in expression from 1 to 12 hours. In late-gestation E19 scarring
      fetal wounds, lysyl oxidase increased 1.8-fold at 8 hours and 2-fold at 12 hours,
      which was significantly greater than the changes observed in E17 scarless wounds
      (p < 0.01 for each). CONCLUSIONS: Lysyl oxidase has greater expression in E19
      late-gestation wounds that heal with scar compared with E17 early-gestation
      scarless wounds. This suggests a role for lysyl oxidase in scar formation.

PMID- 17016179
TI  - A novel perfluoroelastomer seeded with adipose-derived stem cells for soft-tissue
      repair.
AB  - BACKGROUND: There is a need for engineered soft tissue in reconstructive surgery,
      particularly after tumor removal. An ideal implant that will provide structural
      support and a favorable environment for growing cells is a key element in the
      process of tissue engineering. Nonbiodegradable materials that become well
      incorporated within the new tissue are a good solution, but many such materials
      do not have a surface favorable for cell adherence and proliferation. The authors
      hypothesized that the modification of the pore size in a novel fluoropolymer
      would improve the adherence and enhance the proliferation of adipose-derived stem
      cells. METHODS: Fluoropolymers with two varying pore size ranges were examined.
      Fluoropolymer compound U48 (pore size, 100 to 180 microm) and fluoropolymer
      compound P54 (pore size, 10 to 55 microm) were seeded with human adipose-derived
      stem cells, and cell adherence to the material was measured after 4 hours and
      cell proliferation was measured after 72 hours. Cell-seeded constructs were
      implanted subcutaneously in a nude mouse model for 30 days. RESULTS:
      Fluoropolymer surface treatment with fibronectin improved the attachment of
      adipose-derived stem cells to the well plates but did not improve attachment to
      the fluoropolymer, regardless of pore size. Fluoropolymer U48 increases the
      adherence and provides a favorable surface for proliferation of adipose-derived
      stem cells. CONCLUSIONS: After subcutaneous implantation into nude mice, tissue
      growth was observed in the fluoropolymer samples with the larger pore size. The
      characteristics of this new material will allow for future clinical applications
      in plastic and reconstructive surgery.

PMID- 17016181
TI  - Pectoralis major musculocutaneous flap in oropharyngeal reconstruction:
      revisited.
AB  - BACKGROUND: Free tissue transfer is now favored for head and neck reconstruction
      following cancer resection. Its success rate is rising with the obvious advances
      in microsurgery. The pectoralis major musculocutaneous flap, a former workhorse
      in head and neck reconstruction, has been overlooked and criticized because of
      its seemingly high rate of complications and cosmetic inferiority, but it is
      still being used by many surgeons and plays an important role in head and neck
      reconstruction. METHODS: The authors reviewed 34 pectoralis major
      musculocutaneous flap cases and 18 free flap cases (12 radial forearm flaps, six
      rectus abdominis flaps) involving oropharyngeal reconstruction. Flap necrosis,
      fistula formation, and operative times were compared. The pectoralis major
      musculocutaneous flap was elevated in true island type with maximal
      skeletonization of the pectoral branch of the thoracoacromial vessels. RESULTS:
      In pectoralis major musculocutaneous cases, all defects were reconstructed
      successfully, with only two cases of partial necrosis that were managed
      conservatively. Among the free flaps, two resulted in total flap loss and were
      subsequently replaced with pectoralis major musculocutaneous flaps. Fistula
      formation did not occur in any case in either group. Mean operative time for
      pectoralis major musculocutaneous flap preparation was 76 +/- 7 minutes; that for
      free flap preparation was 145 +/- 11 minutes. CONCLUSIONS: Technical refinements
      and meticulous procedures minimized necrosis of the pectoralis major
      musculocutaneous flap and guaranteed the success of the reconstruction. The free
      flap is an excellent method for oropharyngeal reconstruction, but the refined
      pectoralis major musculocutaneous flap can also produce acceptable results with
      minimal complications. In some instances, the pectoralis major musculocutaneous
      flap is not only an alternative to the free flap but a better choice that
      presents less risk to the patient.

PMID- 17016183
TI  - Long-term outcome of skull base surgery with microvascular reconstruction for
      malignant disease.
AB  - BACKGROUND: Successful resection of malignant skull base disease depends
      implicitly on the ability to reconstruct the resulting defects in the
      craniovisceral diaphragm, to support neural structures, and to prevent ascending
      intracranial infections. Microsurgery reliably achieves these objectives and has
      increased the scope of curative oncologic surgery. The authors assessed the
      reconstructive results and the long-term oncologic outcome of patients having
      skull base surgery with free tissue transfer. METHODS: A retrospective review of
      cases between 1989 and 2001 was undertaken. Demographics, histology, surgical
      management, complications, locoregional control, and survival were analyzed.
      RESULTS: Predominantly male patients (n = 53; 62 percent) with an average age of
      60 years had microvascular reconstruction following oncologic surgery. There was
      a preponderance of cutaneous malignancies (56 percent), and most lesions involved
      the anterior skull base (53 percent). Tumors were mostly resected with a combined
      intracranial or extracranial approach, and reconstruction was undertaken with
      radial forearm, rectus abdominis, or latissimus dorsi flaps with 94 percent
      success. Complications occurred in 23 percent of patients, and no specific risk
      factors for developing intracranial complications were identified. Specifically,
      extensive reconstructions did not increase the complication rate. The 5-year
      locoregional control and survival rates were 74 percent and 60 percent,
      respectively. A positive resection margin significantly increased the risk of
      locoregional recurrence and worsened disease-specific survival on Cox regression.
      Survival was also influenced by grade of malignancy. CONCLUSIONS: Microsurgery is
      highly reliable for reconstructing defects resulting from oncologic resections of
      the cranial base. It can and should be undertaken using a small number of highly
      dependable flaps.

PMID- 17016185
TI  - The bipedicled and bipartite latissimus dorsi free and perforator flap: an
      anatomic study.
AB  - BACKGROUND: The purpose of this study was to search for an enhanced blood supply
      in the distal one third of the latissimus dorsi and, thus, to have a closer look
      at the muscular branches of the intercostal vessels. METHODS: The muscle branches
      to the latissimus dorsi muscle arising in the "costal groove" segment of the
      three lowermost intercostal vessels (ninth to eleventh interspaces) were
      identified bilaterally in 28 fixed hemithoraces (84 interspaces). In the
      interspaces, the perforators 0.5 mm or greater were localized and dissected free
      to their junction with the intercostal source vessels. The number of branches was
      recorded and external diameters of branches and source vessels were measured.
      RESULTS: At least one big muscular branch to the latissimus dorsi was found in
      every hemithorax. In the tenth and eleventh interspaces, at least one branch was
      found in all cases; in the ninth interspaces, one branch was found in 93 percent
      of cases. A second big branch was found in approximately half of the ninth and
      tenth interspaces, and in one fourth of the eleventh interspaces. The external
      mean diameter of the muscular branches at their branching point from the source
      vessel was 1.5 mm for the artery and 1.8 mm for the vein. CONCLUSIONS: The
      versatility of the latissimus dorsi muscle can be enhanced by including
      intercostal vascular branches of the intercostal groove segment into the flap
      design. The latissimus dorsi can be harvested as a bipedicled free flap; thus, it
      allows the harvest of two separate bipartite, independent muscle,
      musculocutaneous, or perforator flaps.

PMID- 17016186
TI  - Donor-site morbidity of the radial forearm free flap after 125 phalloplasties in
      gender identity disorder.

PMID- 17016187
TI  - The segmental gastrocnemius muscle flap: anatomical study and clinical
      applications.
AB  - BACKGROUND: The versatility of the gastrocnemius muscle for reconstruction of
      defects in the knee region from the upper third of the calf to the lower third of
      the thigh is well known. Possible limitations of this flap include difficulties
      in covering multiple separate wounds in the same area as well as contour
      deformity because of the flap bulkiness. The findings in this study extend the
      versatility of the gastrocnemius muscle flap by splitting each head into two
      segments allowing for the closure of multiple defects. METHODS: Studied was the
      vascular anatomy of 15 fresh cadaveric lower extremities. Contrast material was
      injected into the sural artery and this showed the bifurcation of the pedicle in
      the upper third of the muscle. A constant intramuscular vascular pattern
      represented by two main longitudinal branches permitted the safe division of each
      head. Based on these anatomic studies, segmentation was performed of the
      gastrocnemius muscle flap in 29 patients. In 13 cases were used, one or two
      muscle segments and in 16 cases, three muscle segments were transposed. RESULTS:
      All of the flaps survived. Minor complications, such as wound dehiscence,
      cellulitis, or hematoma, were encountered in seven patients. Except for one
      patient with persistent drainage from osteomyelitic bone, all the wounds closed
      successfully. CONCLUSIONS: The authors report the safe splitting of the distal
      gastrocnemius muscle in 29 patients based on vascular anatomic studies. The
      advantages of gastrocnemius segmentation include the possibility of covering
      multiple defects with less contour deformity.

PMID- 17016188
TI  - Innervated lateral middle phalangeal finger flap for a large pulp defect by
      bilateral neurorrhaphy.
AB  - BACKGROUND: The dorsal middle phalangeal finger flap is a reliable flap. However,
      it requires skin grafting on the whole surface of the dorsum of the middle
      phalanx of the donor finger for an exposed extensor tendon and leaves a
      conspicuous contour deformity at the donor site. In an effort to overcome this
      problem, the authors have been using a heterodigital innervated lateral middle
      phalangeal finger flap for resurfacing sizable defects of the pulp. METHODS:
      Flaps were designed on the lateral ulnar side of the middle finger for five thumb
      defects and the ring finger for two little finger defects. To provide sensation
      to the flap, one nerve fascicle from the direct small branches of the proper
      digital nerve after interfascicular dissection (palmar aspect of the flap) and
      the dorsal branch of the proper digital nerve (dorsal aspect) were identified and
      sectioned proximally, leaving a 1-cm nerve tail attached to the flap. RESULTS:
      These flaps provided sensate coverage with static two-point discrimination values
      of approximately 6 mm. Donor finger morbidity was minimal, and pulp sensation in
      donor fingers was normal in all cases. No donor finger cold intolerance was
      reported in this series. CONCLUSIONS: This described flap supplies glabrous skin
      of nearly normal sensibility. One nerve fascicle from the direct small branches
      of the proper digital nerve and the dorsal branch of the proper digital nerve
      were used for maximal sensation. Donor fingers are cosmetically better than those
      of dorsal middle phalangeal finger flaps because the grafted skin is hidden by an
      adjacent finger.

PMID- 17016190
TI  - Randomized comparison of the single-injection volar subcutaneous block and the
      two-injection dorsal block for digital anesthesia.
AB  - BACKGROUND: Two commonly used methods of digital nerve block with local
      anesthetic are the two-injection dorsal technique and the single-injection volar
      subcutaneous technique. The authors compared these two digital block techniques
      with respect to local anesthetic injection pain and recipient preference of
      anesthetic technique. METHODS: Twenty-seven volunteers had the long finger of
      each hand injected with 2% lidocaine with 1:100,000 epinephrine. The two
      injection dorsal method was used on one long finger and the other long finger
      received the volar single-injection technique. Volunteers completed a pain scale
      for each block and were then asked which technique they would prefer. The area of
      anesthetic skin was assessed in each finger by pinprick testing, and photographs
      were taken. RESULTS: Although there was a lower pain score for the volar single
      injection block, the difference in pain scores between the two techniques was not
      statistically significant. However, 22 of the 27 subjects indicated that they
      would select the volar over the dorsal block if a future block was required, and
      this preference for the volar block was statistically significant. CONCLUSIONS:
      Although the difference in pain scores between the two techniques was not
      statistically significant, volunteers who received both blocks would prefer the
      volar single-injection subcutaneous block if given a choice. Therefore, the
      single-injection volar subcutaneous block is recommended as the technique of
      choice for anesthesia of the digit, except in patients for whom anesthesia over
      the dorsum of the proximal phalanx is required. These patients may prefer a
      supplementary dorsal nerve block or a traditional two-injection block.

PMID- 17016191
TI  - Distraction osteogenesis of the hypoplastic midface using a rigid external
      distraction system: the results of a one- to six-year follow-up.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term stability of
      maxillary distraction osteogenesis by use of a rigid external distraction device,
      based on a 7-year experience. METHODS: Nine patients with severe cleft maxillary
      hypoplasia were treated between January of 1998 and August of 2003. Their ages at
      the time of surgery ranged from 13 to 19 years. Distraction was started at 5 days
      after a Le Fort I osteotomy at a rate of 1 mm per day for 10 to 15 days. All
      patients used the Rigid External Distraction I system. After distraction was
      completed, the device was left in place for another 5 to 6 weeks for bony
      consolidation. When this was completed, an orthodontic face mask was used with
      elastic traction for 5 to 6 weeks. The follow-up period ranged from 1 to 6 years.
      RESULTS: The mean distraction length was 13.6 mm immediately after distraction,
      10.8 mm at 6 months after distraction, and 10.4 mm between the 1- and 6-year
      follow-up period, resulting in relapse rate of 23.0 percent. In three children
      with mixed dentition, the ANB angle ranged from 7.1 to 8.5 degrees immediately
      after distraction, from 2.8 to 4.0 degrees 6 months postoperatively, and from 0.4
      to 1 degree 5 years postoperatively. Therefore, the growth rate of the distracted
      maxilla was lower than that of the mandible in those three children. CONCLUSION:
      The results suggest that greater anterior overcorrection of the hypoplastic
      maxilla is needed in the growing child than in adults to compensate for a partial
      relapse and growth deficit.

PMID- 17016192
TI  - Segmental LeFort I surgery: turning a predicted soft-tissue failure into a
      success.

PMID- 17016193
TI  - Laserbrasion: the combination of carbon dioxide laser and dermasanding.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy of laserbrasion
      (the combination of carbon dioxide laser and dermasanding) in the removal of
      heavy perioral wrinkles. METHODS: Ninety patients underwent laserbrasion for
      treatment of heavy perioral wrinkles. They were assessed clinically by the
      surgeon and staff for wrinkle reduction, healing, and complications. A subset of
      26 patients was followed for more than 1 year to assess long-term effects,
      especially hypopigmentation. RESULTS: Laserbrasion was successful in reducing 95
      percent of heavy perioral wrinkles as compared with 75 percent seen previously
      with laser alone. No complications were noted with laserbrasion, and there was no
      significant long-term hypopigmentation. Healing time was quicker for laserbrasion
      (9 days) than for laser alone (12 days). CONCLUSIONS: Laserbrasion is an
      effective and safe method of reducing deep perioral wrinkles. The technique is
      easy to perform and inexpensive for the laser surgeon. Laserbrasion can yield
      better results than the laser alone and has the added benefit of a shorter
      healing time.

PMID- 17016195
TI  - Capsular contracture in subglandular breast augmentation with textured versus
      smooth breast implants: a systematic review.
AB  - BACKGROUND: There are conflicting recommendations in the literature regarding the
      use of textured implants to reduce capsular contracture in subglandular breast
      augmentation. The authors reviewed the literature to evaluate the effectiveness
      of surface texturization in reducing capsular contracture. METHODS: The
      electronic databases MEDLINE, EMBASE and the Cochrane Central Register of
      Controlled Trials were searched for randomized controlled trials comparing
      textured with smooth implants for subglandular breast augmentation. Study quality
      was evaluated, and data were extracted from the relevant studies by two
      reviewers. Outcome measures were reduction in capsular contracture as defined by
      Baker grade, applanation tonometry, and patient self-assessment. Overall, the
      treatment effects were expressed as relative risk for dichotomous data and as
      weighted mean differences for continuous data. RESULTS: Six randomized controlled
      trials were identified with a total of 235 patients (470 breasts). Textured
      implants were associated with less capsular contracture as evaluated by Baker
      grade at 1 year (relative risk, 4.16; 95% CI, 1.58 to 10.96), 3 years (relative
      risk, 7.25; 95% CI, 2.42 to 21.69), and 7 years (relative risk, 2.98; 95% CI,
      0.86 to 10.37) of follow-up. Applanation tonometry used as an objective measure
      of firmness, however, was not sensitive enough to detect any significant
      difference in contractures in the two groups (weighted mean differences, -1.54;
      95% CI, -6.83 to -3.75). Interestingly, the self-assessment questionnaire
      revealed that capsular contracture or firmness is one (albeit a very important
      factor) of many facets in patient overall satisfaction. CONCLUSIONS: This
      systematic review suggests that implant texturization reduces the incidence of
      early capsular contracture in subglandular breast augmentation. However, further
      studies are needed to evaluate the long-term effect of texturization and confirm
      the long-term benefits noted in this study.

PMID- 17016196
TI  - Aesthetic labia minora reduction with inferior wedge resection and superior
      pedicle flap reconstruction.
AB  - BACKGROUND: Aesthetic surgery of female genitalia is an uncommon procedure, and
      of the techniques available, labia minora reduction can achieve excellent
      results. Recently, more conservative labia minora reduction techniques have been
      developed, because the simple isolated strategy of straight amputation does not
      ensure a favorable outcome. This study was designed to review a series of labia
      minora reductions using inferior wedge resection and superior pedicle flap
      reconstruction. METHODS: Twenty-one patients underwent inferior wedge resection
      and superior pedicle flap reconstruction. The mean follow-up was 46 months.
      Aesthetic results and postoperative outcomes were collected retrospectively and
      evaluated. RESULTS: Twenty patients (95.2 percent) underwent bilateral
      procedures, and 90.4 percent of patients had a congenital labia minora
      hypertrophy. Five complications occurred in 21 patients (23.8 percent). Wound
      healing problems were observed more frequently. The cosmetic result was
      considered to be good or very good in 85.7 percent of patients, and 95.2 percent
      were very satisfied with the procedure. All complications except one were
      observed immediately after the procedure. CONCLUSIONS: The results of this study
      demonstrate that inferior wedge resection and superior pedicle flap
      reconstruction is a simple and consistent technique and deserves a place among
      the main procedures available. The complications observed were not unexpected and
      did not extend hospital stay or interfere with the normal postoperative period.
      The success of the procedure depends on patient selection, careful preoperative
      planning, and adequate intraoperative management.

PMID- 17016198
TI  - Neck rejuvenation revisited.
AB  - PURPOSE: Restoration of the aesthetic neck contour is an integral component of
      facial rejuvenation. Multiple deformities of the neck and chin complex can make
      treatment of the cervical region daunting. An algorithmic approach to neck
      rejuvenation based on individual anatomic and clinical analysis is prudent. The
      authors created a simplified anatomic approach to the most common cervical
      deformities encountered in the patient seeking facial rejuvenation. METHODS:
      Retrospective analysis of the senior author's (R.J.R.) technique evolution over
      the last 15 years was performed. The operative techniques used in neck
      rejuvenation were evaluated and the long-term postoperative results were
      reviewed. RESULTS: Recurrent patterns of cervical deformity are present in
      patients presenting for facial rejuvenation. These patterns can be classified
      into categories based on specific anatomic deformities. CONCLUSIONS: Facial
      rejuvenation requires appropriate identification of deformity to effect the
      desired changes. Cervical deformities are classified into clinically useful
      categories based on careful preoperative analysis. A thorough understanding of
      the anatomic bases for the deformities allows the surgeon to choose the
      appropriate treatments to achieve consistent and reliable results.

PMID- 17016200
TI  - Resident selection.

PMID- 17016202
TI  - Gunshot wounds: reconstruction of the lower face by osteogenic distraction.

PMID- 17016204
TI  - Preliminary results of double nerve transfer to restore elbow flexion in upper
      type brachial plexus palsies.

PMID- 17016205
TI  - Breast reconstruction following subcutaneous mastectomy for cancer: a critical
      appraisal of the nipple-areola complex.

PMID- 17016208
TI  - Personal experience following 350 subfascial breast augmentations.

PMID- 17016209
TI  - An ordinary ruler and the Limberg flap: reply.

PMID- 17016211
TI  - In search of a journal.

PMID- 17016212
TI  - Characteristics of tissue-engineered cartilage on macroporous biodegradable PLGA
      scaffold.
AB  - BACKGROUND: The purpose of this study was to establish in vivo culture of
      chondrocytes on biodegradable, poly-D,L-lactic-co-glycolic acid (PLGA) scaffolds
      and to analyze the characteristics of the reconstructed cartilage. METHODS: In
      vitro cultured chondrocytes that were grown on a polyhydroxyethyl methacrylate
      (poly-HEMA) coated dish were seeded onto the PLGA scaffolds to make a cell
      polymer construct before implantation. One cell scaffold construct was carefully
      implanted in the subcutaneous pocket of a nude mouse and another cell-free
      scaffold was implanted in the opposite side of the same nude mouse as the
      control. Morphologic, biochemical, and immunohistochemical characteristics of
      cells cultured within the PLGA constructs were examined after 8 weeks and 16
      weeks of harvesting in the nude mouse. RESULTS: New cartilage began to be
      generated in the period of 8 weeks and the neocartilage formation was
      accomplished in 4 months with the exact dimensions of the original scaffold in
      this in vivo study. All the explants showed the irregular shape of viable
      chondrocytes within normal lacunae and a mature cartilaginous matrix, and they
      positively immunostained for collagen type II. CONCLUSION: The new tissue
      engineered cartilage in vivo on PLGA scaffolds displayed the biochemical
      characteristics of cartilage tissue, and it showed chondrocyte-specific
      phenotypes and morphology that were similar to the native cartilage.

PMID- 17016213
TI  - Repetitive transcranial magnetic stimulation for tinnitus: a case study.
AB  - OBJECTIVES/HYPOTHESIS: Correlate subjective improvements in tinnitus severity
      with restoration of cortical symmetry and sustained attention after
      neuronavigated low-frequency, repetitive transcranial magnetic stimulation
      (rTMS). STUDY DESIGN: Case study. METHODS: Positron emission tomography and
      computed tomography imaging (PET-CT) guided rTMS was performed on a 43-year-old
      white male with more than a 30 year history of bilateral tinnitus. rTMS was
      administered to the area of increased cortical activation visualized on PET-CT at
      a rate of 1 Hz for 30 minutes (1,800 pulses/session) for each of 5 consecutive
      days, with optimization applied on day 5 using single pulses of TMS to
      temporarily alter tinnitus perception. Subjective tinnitus severity was rated
      before and after rTMS using the tinnitus severity index with analogue scale.
      Attention and vigilance were assessed before and after therapy using the
      psychomotor vigilance task (PVT), a simple reaction time test that is sensitive
      to thalamocortical contributions to sustained attention. Posttherapy PET-CT was
      used to evaluate any change in asymmetric cortical activation. RESULTS: The most
      marked reduction in tinnitus severity occurred after rTMS optimization; this
      persisted up to 4 weeks after rTMS. PVT testing showed the patient exhibited a
      statistically significant improvement in mean slowest 10% reaction times after
      rTMS (P = .004). PET-CT imaging 2 days after the cessation of rTMS showed no
      changes in cortical blood flow or metabolic asymmetries. CONCLUSIONS: Low
      frequency rTMS applied to the primary auditory cortex can reduce tinnitus
      severity, with rTMS optimization yielding the most favorable results. Beneficial
      changes occurring in the patient's slowest reaction times suggest that
      attentional deficits associated with tinnitus may also respond to low-frequency
      rTMS.

PMID- 17016214
TI  - Revision total hip arthroplasty: the patient's perspective.
AB  - We evaluated a consecutive series of patients followed for at least 1 year after
      revision total hip arthroplasty. We surveyed 488 patients treated at three
      referral centers from 1998 to 2002. An experienced medical interviewer contacted
      patients and rated their degree of satisfaction with the original and revision
      arthroplasties, the reason of original arthroplasty failure, and their
      expectations for revision arthroplasty longevity. Surveys were completed on 320
      of the 488 patients (66%). A member of the research team reviewed patients'
      operative reports, clinical records, and radiographs to determine the diagnosis
      at revision, procedure performed, and the most likely cause of failure. Patient
      satisfaction with the primary procedure was directly related to the time to
      revision. Most patients (214 of 320; 67%) expected their revision to last longer
      than their primary arthroplasty regardless of revision diagnosis or how long the
      primary procedure lasted before revision. The surgeons' failure assessments
      agreed with the patients' failure assessments only 36% of the time. Although the
      majority of patients (262 of 320; 82%) were satisfied with the results of the
      revision procedure, most did not agree with their surgeon as to why the original
      arthroplasty failed, and most had unrealistic expectations regarding revision
      longevity.

PMID- 17016215
TI  - Comprehensive morphologic evaluation of the hip in patients with symptomatic
      labral tear.
AB  - A torn acetabular labrum is a well-documented source of hip pain, but the
      mechanism of injury is debated because the relationship between the bone
      morphology and labral tears is poorly understood. We compared hips with and
      without labral abnormalities to determine the relative incidence of morphologic
      abnormalities. The study group consisted of patients with a labral tear confirmed
      by arthroscopy or arthrotomy at the time of open debridement or periacetabular
      osteotomy. We compared the affected hip with the contralateral, unaffected hip to
      ascertain signs of hip dysplasia and impingement. We observed differences in the
      center edge angle, acetabular depth to width index, acetabular index of
      elevation, femoral head extrusion, lateral and superior subluxation, Sharp's
      angle, peak to edge distance, and acetabular retroversion. Similar differences
      occurred in the subgroup analyses. Symptomatic labral tears correlated with
      abnormal hip morphology as reflected by radiographic measurements of dysplasia
      and impingement. This relationship occurred in patients with hip dysplasia and
      patients without obvious femoral head uncovering. Our findings suggest abnormal
      hip morphology may be a risk factor for labral tears.

PMID- 17016216
TI  - Hydroxyapatite-coated femoral components: 15-year minimum followup.
AB  - Hydroxyapatite-coated femoral components were introduced to enhance fixation, but
      concerns were raised about whether the coating would be maintained over time. We
      therefore determined the long-term clinical and radiographic results of a
      proximally hydroxyapatite-coated femoral component and compared the mechanical
      failure rate to other fixation methods at similar lengths of followup. The study
      group, culled from a large, multicenter prospective study population, consisted
      of 146 patients (166 hips) with followup of 15 to 18 years. Average age at time
      of the index procedure was 51 years, and the most common diagnoses were
      osteoarthritis (71%) and osteonecrosis (11%). Average Harris hip scores were 42.7
      preoperatively and 91.5 at most recent followup. Radiographically, one stem
      showed stable fibrous fixation, and all other unrevised stems were bony stable.
      Of 13 stem revisions in the study population, only one stem has been revised for
      aseptic loosening. Forty-nine percent of hips have an osteolytic lesion in
      proximal areas of Gruen Zones 1, 7, 8, or 14 only. Both the femoral aseptic
      revision and mechanical failure rates are 0.6% at 15-year minimum followup. The
      data demonstrate excellent long-term survivorship of this hydroxyapatite-coated
      femoral component used in a relatively young patient group.

PMID- 17016217
TI  - Acetabular revision with the Contour antiprotrusio cage: 2- to 5-year followup.
AB  - The Contour cage introduced in 1999 was designed to improve fixation and provide
      a surface for bone ongrowth. To determine whether the rates of radiographic
      loosening and/or revision have been reduced with the Contour design, we
      retrospectively reviewed the medical records and radiographs of 29 patients
      (average age, 68.1 years) undergoing 31 acetabular revisions with a Contour cage.
      The minimum followup was 24 months (mean 30 months, range, 24-58 months). Based
      on the Paprosky classification, two hips were Type 2B, seven were Type 3A, and 22
      were Type 3B. Two hips (7%) were revised for loosening; one of these two was also
      infected. An additional five hips (16%) had signs of radiographic loosening. The
      mean Harris hip score improved from 45 to 80; functional scores improved less
      than the pain scores. Only 14 hips (45%) had an excellent or good clinical result
      and three of these 14 hips had radiographic signs of loosening; presuming these
      three hips eventually fail, only 35% of the hips had a good or excellent result.
      We found an association between number of previous surgeries and radiographic
      loosening and revision. Our data suggest the Contour cage offers little advantage
      over other antiprotrusio cages and highlight the substantial limitations of
      current methods available for treating patients with extensive acetabular bone
      loss.

PMID- 17016218
TI  - Nonsurgical management of osteolysis: challenges and opportunities.
AB  - Osteolysis remains a common mode of total hip arthroplasty failure. In vitro and
      animal models have been used to determine the pathophysiology of osteolysis by
      carefully dissecting the biochemical pathways leading to particulate wear debris
      and periprosthetic bone loss. Numerous cytokines and inflammatory mediators,
      including TNF-alpha and IL-1, are critical participants in this cascade and may
      represent prime targets for pharmacologic intervention. Osteoclasts, the end
      effector cells involved in the osteolytic process, also represent potential
      targets. Cell surface receptors on osteoclast precursors, such as receptor
      activator of NF-kappaB (RANK) (on osteoclasts) and RANK-ligand (RANKL) (on
      stromal cells), provide opportunities to arrest osteoclast maturation. Enhancing
      the naturally occurring osteoprotegerin is another recent attempt at modulating
      osteoclast behavior and a possible target for pharmacologic therapies. Other
      nonoperative strategies include intercepting tumor necrosis factor-alpha
      activity, interfering with the RANK-RANKL interaction necessary for osteoclast
      development and maturation, bisphosphonate therapy, and using viral vectors to
      deliver genes. Although each of these approaches has potential benefits, there
      are substantial challenges to effective implementation. Until there is convincing
      evidence of efficacy in human clinical trials, we recommend vigilant screening
      and appropriate surgery with component loosening or substantial likelihood of
      loosening, periprosthetic fracture, or major bone loss.

PMID- 17016219
TI  - The treatment of pelvic discontinuity with acetabular cages.
AB  - We sought to determine if acetabular cages prevented rerevision and loosening in
      acetabular reconstructions in the setting of pelvic discontinuity. We followed 15
      patients with 16 acetabular cage reconstructions for an average 5 years (range, 2
      8 years). Acetabular classifications included two Type 2C, six Type IIIA, and
      eight Type IIIB. We assessed Merle d'Aubigne scores, rerevisions, radiographic
      loosening, and complications. We treated seven patients with structural allograft
      and six patients with cancellous allograft. Five hips (31%) were revised or
      resected because of aseptic loosening (4 hips) and sepsis (1 hip) at an average
      46 months. Three additional hips were loose. Merle d'Aubigne scores for pain and
      walking increased from 3.7 points preoperatively to 6.8 points at the final
      followup. Complications included one infection, four nerve palsies, and one
      dislocation. Acetabular cages in the setting of pelvic discontinuity were
      associated with a high failure rate at intermediate-term followup.

PMID- 17016220
TI  - Outcomes of shoulder arthroplasty in Olmsted County, Minnesota: a population
      based study.
AB  - Most studies on shoulder arthroplasty include a diverse group of patients
      presenting to a tertiary care center. Little information is available regarding
      outcomes in a community setting. We reviewed 98 residents (110 shoulders) of
      Olmsted County, Minnesota who had shoulder arthroplasties from 1976 to 2000.
      There were 65 total shoulder arthroplasties and 45 humeral head replacements. The
      most common indications were osteoarthritis for total shoulder arthroplasties
      (48/65) and acute fracture for hemiarthroplasties (27/45). The Neer ratings were
      excellent or satisfactory in 92% of total shoulder arthroplasties and 56% of
      hemiarthroplasties. The 10-year survival rate was 96%. The mean postoperative
      active forward elevation was greater in patients who had a total shoulder
      arthroplasty (132 degrees) compared with a hemiarthroplasty (113 degrees), as was
      external rotation (total shoulder arthroplasties = 58 degrees, humeral head
      replacements = 38 degrees). The outcomes for total shoulder arthroplasty and
      hemiarthroplasty compared favorably with outcomes reported in the literature.
      There was a high rate of satisfactory or excellent results after total shoulder
      arthroplasty for osteoarthritis. Hemiarthroplasty offered less satisfactory
      results, most likely related to the use of this procedure for trauma. This
      information will assist the community surgeon in counseling patients and weighing
      the risks and benefits of a shoulder arthroplasty.

PMID- 17016221
TI  - Clinical impact of obesity on stability following revision total hip
      arthroplasty.
AB  - Similar outcomes have been reported for obese and nonobese patients after primary
      total hip arthroplasty (THA), indicating obesity is not a contraindication to
      total hip arthroplasty. However, obese patients may develop implant failure and
      require revision THA. We compared the outcomes of revision THA in a matched
      cohort of obese and nonobese patients. Patients were stratified into two groups
      according to BMI (body mass index, kg/m2): Group 1 included 31 obese patients
      (BMI > 35), and Group 2 included 62 nonobese patients (BMI < 30) matched on age,
      gender, and type of revision procedure. Obese patients had increased total
      operating room time, a higher rate of discharge to a skilled nursing facility,
      and a higher dislocation rate (p < 0.05). Seven patients in the obese group
      underwent revision surgery, six of whom underwent additional reoperations to
      treat recurrent postoperative dislocation. Obese patients should be counseled
      about the increased risk of dislocation that can occur after revision THA.

PMID- 17016222
TI  - Surgical variables affect the mechanics of a hip resurfacing system.
AB  - Recent clinical studies have linked failure to surgical variables of stemmed hip
      resurfacing systems. We used finite element analysis to investigate the effects
      of implant position, stem orientation, and extent of fixation both on the local
      stresses and strains associated with implant loosening, neck fracture, and stem
      fracture, as well as on the load transfer distribution in the bone-implant
      system. The range of peak stress in the cement was reduced from 11 to 13 MPa for
      the varus stem to 3.2 to 4.2 MPa for the valgus stem. The range of peak strain in
      the bone was also reduced from -0.35% to -0.45% strain for the varus stem to 
      0.19% to -0.27% strain for the valgus stem, but only when reamed cancellous bone
      remained exposed. Peak stresses in the stem were low for all cases. Additionally,
      the implant's load transfer distribution was generally insensitive to all
      variables examined and the femoral head was substantially unloaded. Our data
      indicate the local stresses and strains associated with implant loosening and
      neck fracture were reduced by placing the implant in a valgus orientation and
      covering reamed cancellous bone, but unloading of the femoral head, found for all
      variables examined, may lead to adverse bone remodeling.

PMID- 17016223
TI  - Tribology of alternative bearings.
AB  - The tribological performance and biological activity of the wear debris produced
      has been compared for highly cross-linked polyethylene, ceramic-on-ceramic, metal
      on-metal, and modified metal bearings in a series of in vitro studies from a
      single laboratory. The functional lifetime demand of young and active patients is
      10-fold greater than the estimated functional lifetime of traditional
      polyethylene. There is considerable interest in using larger diameter heads in
      these high demand patients. Highly cross-linked polyethylene show a four-fold
      reduction in functional biological activity. Ceramic-on-ceramic bearings have the
      lowest wear rates and least reactive wear debris. The functional biological
      activity is 20-fold lower than with highly cross-linked polyethylene. Hence,
      ceramic-on-ceramic bearings address the tribological lifetime demand of highly
      active patients. Metal-on-metal bearings have substantially lower wear rates than
      highly cross-linked polyethylene and wear decreases with head diameter. Bedding
      in wear is also lower with reduced radial clearance. Differential hardness
      ceramic-on-metal bearings and the application of ceramic-like coatings reduce
      metal wear and ion levels.

PMID- 17016224
TI  - Osteogenic gene expression decreases in stromal cells of patients with
      osteonecrosis.
AB  - Nontraumatic osteonecrosis is related to alcohol and glucocorticoid with unknown
      pathogenesis. Increased adipogenesis decreases bone morphogenetic protein 2
      (BMP2) gene expression after glucocorticoid treatment. Lovastatin enhances BMP2
      gene expression in rodents, reverses the effects of glucocorticoids on bone, and
      prevents glucocorticoid-induced osteonecrosis in chickens and humans. We
      hypothesized patients with osteonecrosis are more susceptible to glucocorticoid
      treatment than patients without osteonecrosis. Marrow stromal cell cultures from
      14 patients with osteonecrosis, and 10 patients without osteonecrosis were
      treated with dexamethasone (0.1 micromol/L), lovastatin (1 micromol/L), or
      combined treatment. BMP2 and osteocalcin gene expression were evaluated by
      reverse-transcriptase polymerase chain reaction and real-time polymerase chain
      reaction. The suppression of BMP2 by dexamethasone was more pronounced and the
      enhancement by lovastatin was less pronounced in the osteonecrosis group.
      Dexamethasone suppressed osteocalcin in the osteonecrosis group. Among the
      subgroups of osteonecrosis, suppression of BMP2 and osteocalcin by dexamethasone
      occurred in glucocorticoid-induced osteonecrosis group. Our data suggest
      individuals who are more susceptible to a glucocorticoid-induced decreases in
      BMP2 and osteocalcin gene expression are more likely to have osteonecrosis,
      especially glucocorticoid-induced osteonecrosis.

PMID- 17016225
TI  - Femoral head blood flow during hip resurfacing.
AB  - Preserving femoral head vascularity during hip resurfacing may avoid femoral neck
      fractures and late femoral loosening. The posterior approach and notching of the
      femoral neck influence femoral head perfusion. However, it is not known if
      standard preparation of the femoral head during hip resurfacing can disrupt blood
      flow. Ten patients (10 hips) with advanced osteoarthritis having metal-on-metal
      hip resurfacing by means of a vascular-preserving surgical approach had femoral
      head blood flow measurements using laser Doppler flowmetry. Nine hips had a mean
      decrease of 70% in femoral head blood flow after standard reaming and
      preparation. The data suggest femoral head reaming during hip resurfacing
      substantially impacts blood flow to the femoral head and infers the extra osseous
      blood supply is still important in the arthritic femoral head. To avoid damaging
      the retinacular vessels, surgeons should direct the cylindrical reamer
      superolaterally staying as close as possible to the inferomedial neck.

PMID- 17016226
TI  - Tumor necrosis has no prognostic value in neoadjuvant chemotherapy for soft
      tissue sarcoma.
AB  - Neoadjuvant chemotherapy for treatment of soft tissue sarcomas is controversial,
      and the correlation between local recurrence and survival is unclear. Histologic
      necrosis is a well-documented predictor of survival in patients with malignant
      bone tumors; however, the association is unknown in patients with soft tissue
      sarcomas. We assessed the prognostic significance of tumor necrosis for treatment
      of soft tissue sarcomas. We retrospectively collected data from 82 patients who
      received neoadjuvant chemotherapy for treatment of soft tissue sarcomas of the
      extremities. Patients had wide resections if tumors were high-grade, deep to the
      investing fascia, and had clear margins. We quantified the amount of necrosis and
      analyzed the relationship with local recurrence and overall survival. At an
      average followup of 65 months (range, 24-154 months), the 5-year local recurrence
      rates for patients with less than 95% and 95% or greater necrosis were 20% and
      33%, respectively. The overall 5-year survivorship rates for patients with less
      than 95% necrosis and 95% or greater necrosis were 82% and 78%, respectively.
      There was no difference in recurrence-free survival or overall patient survival
      based on the amount of histologic necrosis. Tissue necrosis from neoadjuvant
      chemotherapy does not seem to predict outcome in soft tissue sarcomas.

PMID- 17016227
TI  - Role of capsular repair on dislocation in revision total hip arthroplasty.
AB  - Dislocation remains one of the most common complications after revision total hip
      arthroplasty (THA). In contrast to primary THA the posterior capsule has been
      routinely excised to provide better visualization, but its role in preventing
      dislocation has been overlooked. We reviewed 69 patients (79 hips) patients who
      had revision THA with a posterolateral approach to determine if closing the
      posterior capsule resulted in a fewer dislocations. We followed the patients for
      a minimum of 24 months (mean 57 months, range, 24-120 months). Two (2.5%) hips
      dislocated. Both dislocated anteriorly in the immediate postoperative period. One
      dislocation was from implant malposition and the other occurred in a high risk
      patient. There were no posterior dislocations and no patients reported any hip
      subluxation. The historically high dislocation rates with the posterolateral
      approach can be reduced by carefully balancing soft tissues, ensuring correct
      implant alignment, meticulously closing the posterior capsule, and reattaching
      the external rotators.

PMID- 17016228
TI  - The basis for a second-generation highly cross-linked UHMWPE.
AB  - Highly cross-linked ultra-high molecular weight polyethylene (UHMWPE) decreases
      wear at the hip by more than 50% compared with conventional UHMWPE. However,
      melted highly cross-linked polyethylene may be susceptible to fatigue cracking,
      and annealed highly cross-linked polyethylene may be susceptible to in vivo
      oxidation. The second-generation highly cross-linked UHMWPE (X3 HXPE) uses a
      sequential irradiation and annealing process. It preserves mechanical strength
      properties and has the highest survivorship in functional fatigue testing. The
      free radical content is low, and its performance under accelerated aging is the
      same as virgin UHMWPE. Hip simulator studies with 32-mm acetabular components
      demonstrated 97% wear reduction compared with conventional UHMWPE, and 62%
      compared with a clinically successful first-generation annealed highly cross
      linked polyethylene. The crystallinity, density, and tensile strength of the X3
      HXPE material was unchanged by oxidative challenge. X3 HXPE material articulating
      on cobalt-chromium alloy yields a volumetric wear rate very similar to that of
      metal-on-metal articulations, but eliminates the concerns of metal ion release.
      Wear particles generated from the X3 HXPE were the same size as those produced
      from conventional UHMWPE. Preliminary results suggest X3 HXPE can be used for
      cups larger than 36 mm.

PMID- 17016229
TI  - Surgical management of cervical spine osteoblastomas.
AB  - The treatment of cervical spine osteoblastomas requires complex therapeutic and
      reconstructive strategies depending on the tumor's location, local
      aggressiveness, and proximity to the surrounding neurovascular structures.
      Despite careful removal, lesions recur in as much as 10% of patients.
      Preoperative embolization is useful to minimize intraoperative bleeding and
      decrease the relapse of vascular tumors, but its role in osteoblastoma surgery is
      yet to be defined. We asked whether preoperative embolization with marginal
      resection would lead to osteoblastoma recurrence, and whether marginal excision
      with reconstruction would improve neurologic symptoms. We retrospectively
      analyzed a consecutive series of patients with cervical spine osteoblastoma,
      treated by one surgeon with a combined approach of preoperative embolization,
      marginal excision, and spinal reconstruction. One of nine patients presented with
      a monoradiculopathy, whereas only two patients presented with symptomatic spinal
      cord compression. At followup, all patients showed neurologic improvement, no
      tumor relapse, and adequate bony healing. Followup imaging studies showed
      cervical alignment was maintained. Although we report only a small uncontrolled
      cohort, the data suggest preoperative embolization and a tumor-free margin are
      consistent with a prolonged disease-free interval or complete tumor eradication.

PMID- 17016230
TI  - Does celecoxib have an adverse effect on bone remodeling and ingrowth in humans?
AB  - Although celecoxib may provide perioperative pain relief, the effect of the short
      term use of celecoxib on bone ingrowth into porous-coated devices has not been
      previously studied in humans. Bone ingrowth into titanium and tantalum plugs was
      measured in nine patients who underwent staged bilateral total knee arthroplasty
      (TKA) and were taking celecoxib as part of a perioperative pain relief protocol.
      Patients were given tetracycline to measure the mineral apposition rate before
      and after celecoxib administration. Time zero plugs were implanted and retrieved
      during the first TKA, and 12 weeks later the contralateral implanted plugs were
      retrieved at the second TKA. The mineral apposition rate was similar for the
      titanium (0.97 microm per day) and the tantalum (1.15 microm per day) plugs at 12
      weeks as was bone ingrowth (886 microm versus 632 microm, respectively).
      Celecoxib does not seem to inhibit bone ingrowth or bone formation.

PMID- 17016231
TI  - Rationale for low-molecular-weight heparin prophylaxis after total knee
      arthroplasty.
AB  - Low-molecular-weight heparin has been studied extensively in total knee
      arthroplasty (TKA) and provides highly effective and safe prophylaxis against
      deep venous thrombosis (DVT). Low-molecular-weight heparin received the highest
      rating (A1) in the American College of Chest Physicians recommendations for DVT
      prophylaxis after elective TKA. Prevalence of DVT with low-molecular-weight
      heparin prophylaxis was 33% in TKA data pooled from six randomized studies, with
      a proximal DVT rate of 7.1%. A metaanalysis reported a 2.4% rate of major
      bleeding with low-molecular-weight heparin. Low-molecular-weight heparin, given
      by subcutaneous injection, can be started before surgery or after surgery. A
      synthetic pentasaccharide (fondaparinux), which received an A1 rating in the
      American College of Chest Physicians recommendations, also is available. As with
      all treatments, the benefit must be considered against the risk when using these
      anticoagulants.

PMID- 17016232
TI  - Complement activation associates with saccular cerebral artery aneurysm wall
      degeneration and rupture.
AB  - OBJECTIVE: Saccular cerebral artery aneurysm (SCAA) wall degeneration and
      inflammatory cell infiltrations associate with aneurysm rupture and subarachnoid
      hemorrhage, resulting in a devastating form of stroke. The complement system is
      the key mediator of inflammation and household processing of injured tissue. We
      studied how complement activation associates with SCAA wall degeneration and
      rupture to better understand the pathobiology of SCAA wall rupture. METHODS:
      Unruptured (n = 26) and ruptured (n = 32) SCAA fundi resected after microsurgical
      clipping were studied by immunostaining for complement activation (membrane
      attack complex [MAC]) and by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling reaction for related cell death.
      Complement activation was correlated with clinical and other histological
      parameters. Electromicroscopy and immunoelectron microscopy were used for
      locating MAC depositions at the ultrastructural level. RESULTS: MAC localized
      consistently in a decellularized layer in the outer SCAA wall, and was found in
      all SCAA samples. The percentage of MAC-positive area relative to the total SCAA
      wall surface area (range, 5-77%) was greater in ruptured (n = 25; median, 39%)
      than in unruptured SCAAs (n = 18; median, 20%; P = 0.005). It also associated
      significantly with SCAA wall degeneration (P < 0.001), de-endothelialization(P <
      0.001), and CD163+ macrophage (P = 0.023) and T-lymphocyte (P = 0.030)
      infiltrations. Apoptotic terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling-positive nuclei and MAC were located
      at the same wall areas in four out of 14 double-stained samples, but no double
      positive cells were found. Electromicroscopy and immunoelectron microscopy of an
      unruptured SCAA showed cell death in the MAC-positive layers in the outer SCAA
      wall. CONCLUSION: These data suggests that complement activation and MAC
      formation are involved in SCAA wall degeneration and rupture.

PMID- 17016233
TI  - Variant of the CHEK2 gene as a prognostic marker in glioblastoma multiforme.
AB  - OBJECTIVE: Germline mutations of the CHEK2 tumor suppressor gene have been found
      in families with the Li-Fraumeni syndrome (LFS). Patients with LFS experience a
      variety of cancers, including malignant astrocytomas. We investigated a potential
      role for a CHEK2 gene polymorphism in glioblastomas. METHODS: A genetic
      polymorphism of the CHEK2 gene (CHEK2 SNP rs2017309 A/T) was genotyped in a
      series of glioblastoma patients (n = 213) and population controls (n = 192).
      Subsets of tumors were analyzed for loss of heterozygosity 22q(n = 66), loss of
      heterozygosity CHEK2 (n = 53), CHEK2 expression (n = 21), and CHEK2 coding
      sequence alterations (n = 18). CHEK2 SNP rs2017309 genotyping findings and
      traditional clinicopathological parameters were correlated with the patients'
      prognoses. RESULTS: No association between the CHEK2 SNP and glioblastoma
      formation was observed. No CHEK2 coding sequence aberrations or tumors completely
      lacking CHEK2 protein were identified. However, the presence of the CHEK2
      rs2017309 A allele was significantly associated with an adverse prognosis (P =
      0.034), particularly among patients undergoing postoperative chemotherapy and
      radiotherapy (n = 28, median survival 10.5 versus 15.5 mo, P = 0.008). We could
      confirm the patients' age, Karnofsky Performance Scale score, and postoperative
      radiotherapy and chemotherapy (all P < 0.0001, log-rank test) as decisive
      prognostic factors. CONCLUSION: Our data suggest that a CHEK2 gene polymorphism
      might correlate with the prognosis of glioblastoma patients. These findings may
      point to an as yet unrecognized role for the CHEK2 gene in glioblastomas.

PMID- 17016234
TI  - Prevalence of risk factors for hepatitis C virus in HIV-infected and
      HIV/hepatitis C virus-coinfected patients.
AB  - METHODS: A sample of patients with HIV completed a questionnaire identifying
      their demographic characteristics and risk factors for hepatitis C virus (HCV). A
      chart review was conducted to confirm the information obtained using the
      questionnaire. Risk factors associated with coinfection status at alpha level of
      0.1 in univariate analysis were entered into a multivariate Cox regression model.
      RESULTS: Of the 242 HIV-positive patients analyzed, 168 were HIV-infected and 74
      were HIV/HCV-coinfected. Risk factors that were significantly different between
      HIV-monoinfected and HIV/HCV-coinfected subjects included intravenous drug use,
      snorting drugs, sharing razors or toothbrushes, being in prison, the presence of
      one or more tattoos, sex for money or drugs, sex with an intravenous drug user
      and man who has sex with men. In a multivariate regression model, only
      intravenous drug use remained as a significant risk factor/predictor of HCV/HIV
      coinfection. A subanalysis identified risk factors more prevalent among
      coinfected men who have sex with men, including intravenous drug use, sharing
      razors/toothbrushes, tattoos, sex for money or drugs, sex with an intravenous
      drug user, and a history of having 11 or more sexual partners. A history of
      having had a sexually transmitted disease and 11 or more sex partners was more
      prevalent among HIV-monoinfected men who have sex with men. CONCLUSIONS: HIV/HCV
      coinfection was associated with intravenous drug use but not with sexual risk
      factors.

PMID- 17016235
TI  - Low prevalence of penile wetness among male sexually transmitted infection clinic
      attendees in London.
AB  - OBJECTIVE: To determine the prevalence of penile wetness among STI clinic
      attenders in London. STUDY DESIGN: A total of 480 consecutive men were examined
      clinically to detect whether penile wetness, defined as the clinical observation
      of a uniform diffuse layer of moisture on the surface of the glans and coronal
      sulcus, was present. RESULTS: Penile wetness was observed in 30 (6.3%), including
      29 (8.3%) of uncircumcised and 1 (0.8%) of circumcised men (Relative risk 10.54
      (95% CI 1.45-76.6, P = <0.001) (Fisher's Exact test) and in 14/34 (41.2%) of men
      with balanitis. Penile wetness was observed in 9.2% Asian, 7% Caucasian, 3% of
      black men, and 6.3% of homosexuals, and in 14/34 (8.2%) of men with clinical
      balanitis compared with 8/244 (3.3%) with no STI diagnosis (P = <0.001).
      CONCLUSIONS: The prevalence of penile wetness was low in this population of STI
      clinic attenders in London, much lower than in Durban, South Africa. Further
      studies of male genital hygiene are warranted.

PMID- 17016236
TI  - Partner notification for sexually transmitted diseases in Peru: knowledge,
      attitudes, and practices in a high-risk community.
AB  - OBJECTIVES: Notification and treatment of sex partners after diagnosis of a
      sexually transmitted disease (STD) is essential to reduce reinfection and further
      transmission. GOAL: The goal of this study was to determine the prevalence of
      partner notification and subsequent health-seeking behavior in a high-risk
      population in Lima, Peru. STUDY DESIGN: STD-infected participants of an HIV/STD
      prevention trial completed a questionnaire concerning partner notification.
      RESULTS: Of the 502 STD-positive subjects, 287 completed the survey. Among survey
      participants, 65% informed their primary partner and 10.5% informed casual or
      anonymous partners. Reasons for failure to notify varied by partner type and
      included not understanding the importance of partner notification, embarrassment,
      fear of rejection, and inability to locate the partner. When notified,
      approximately one third of all partners sought medical attention. CONCLUSIONS:
      Partner notification in Peru is limited by relationship dynamics, social stigma,
      and limited contact information. Interventions could emphasize the importance of
      notification, improvement of communication skills, and introduce contact tracing
      programs (including Internet-based systems) and expedited partner therapy.

PMID- 17016237
TI  - Predictors of discordant reports of sexual and HIV/sexually transmitted infection
      risk behaviors among heterosexual couples.
AB  - OBJECTIVES: Assessments undertaken as part of couple-based HIV/sexually
      transmitted infection (STI) prevention intervention studies offer opportunities
      to expand our understanding of couple reporting of sexual and HIV/STI risk
      behavior. Increases in heterosexual transmission of HIV worldwide support more
      attention on the quality and use of couple-level sexual risk assessment. STUDY
      DESIGN: This study examined interpartner concordance of self-reported sexual
      behaviors and HIV/STI risk behaviors among 217 women and their main male sexual
      partners at high risk for HIV/STI transmission and further explored specific
      individual and relationship characteristics by partner gender associated with
      discordant reporting of sexual and HIV/STI risk behaviors. RESULTS: Consistent
      with prior studies, findings suggest fair to substantial agreement between
      partners on reports of most sexual and HIV/STI risk behavior, but only poor to
      fair agreement on reports of concurrent sexual behaviors and drug or alcohol use.
      Factors significantly associated with discordant reporting of sexual behaviors
      included length of couple relationship, level of relationship satisfaction,
      female partner's marital status, and male partner's HIV status, ethnicity, and
      age. CONCLUSIONS: Individual- and relationship-level factors predicting
      discordant partner reports of sexual and sexual risk behaviors highlight an
      opportunity to improve couple assessment by anticipating such discrepancies and
      developing effective mechanisms of quality assurance to avoid, address, or better
      explain such discordance in couple data sets.

PMID- 17016239
TI  - Measurement of intracerebral oxygen pressure: practicalities and pitfalls.
AB  - Two probes, using different technologies, are currently available to measure
      tissue oxygen pressure. One of these also measures oxygen pressure, carbon
      dioxide pressure, pH and temperature. Research has delineated normal brain tissue
      oxygen pressure as 25-45 mmHg and ischemic thresholds of less than 10 mmHg that
      are related to ischemic injury. Oxygen pressure measures are correlated with
      other indicators of brain oxygenation such as jugular bulb oxygen saturation and
      near infrared spectroscopy, but are more reliable for detecting regional ischemic
      events. Oxygen pressure is correlated with local blood flow in the brain, and
      treatments that enhance tissue perfusion improve oxygenation.

PMID- 17016240
TI  - Subarachnoid haemorrhage.
AB  - A high percentage of the population has aneurysms of the cerebral vessels, which
      are detected only by chance or after spontaneous rupture. Subarachnoid
      haemorrhage is still a problem because of high morbidity and mortality. Many
      patients do not fully recover neurologically and suffer from physical and
      psychosocial symptoms. The aims of treatment are to prevent the patient from
      rebleeding and to prevent secondary neurological damage. Whereas in former times,
      clipping of the aneurysm was often delayed for days or weeks, early operative
      intervention is the rule today, if the patient is not moribund and if there is no
      significant cerebral oedema. The anaesthetist can support the neurosurgeon with a
      spectrum of different methods of anaesthesia and monitoring, individually
      tailored to the needs of the patient. Most important, however, is a stable
      haemodynamic status, stable and normal intracranial pressure and a sufficient
      cerebral perfusion pressure. Vasospasm is still the main problem, as is early
      rebleeding. To treat this, nimodipine is the drug of choice combined with volume
      therapy, a slightly elevated cardiac output and a modestly elevated blood
      pressure.

PMID- 17016241
TI  - Nitrous oxide in neuroanaesthesia: an appraisal.
AB  - A handful of recent publications have brought relevant contributions to the
      ongoing debate over the use of nitrous oxide in neuroanaesthesia. The present
      article reviews these publications. The question of whether nitrous oxide can be
      safely used in patients with reduced cerebral compliance and the relationship
      between hypocapnic vasoconstriction and nitrous oxide are discussed. The
      implications of the use of nitrous oxide during evoked potentials recording
      (motor evoked potentials and somatosensory evoked potentials) are discussed. The
      possible harmful effect of nitrous oxide in cerebral ischaemia is debated.

PMID- 17016242
TI  - Monitoring and management of the paediatric neurosurgical patient.
AB  - Head injury remains the most common cause of death in children, and tumours of
      the central nervous system are the most common solid tumour encountered. There is
      little class 1 evidence on which to base the monitoring and management of the
      paediatric patient with these conditions, management strategies commonly being
      extrapolated from those in use for adults. However, the clinical outcome for
      these conditions appears to be improving, with evidence suggesting that this
      improvement is being achieved by the management of these children in specialist
      centres.

PMID- 17016243
TI  - Anesthesia and epilepsy.
AB  - The patient with epilepsy is an anesthetic challenge. New drugs and surgical
      procedures are being used to treat epilepsy. Certain anesthetics have been
      reported to cause perioperative seizures. This discussion will focus on advances
      in the treatment of epilepsy, as well as the pro- and anti-convulsant effects of
      the newer anesthetic agents.

PMID- 17016244
TI  - Imaging and interventional neuroradiology.
AB  - Technical innovations in neuroimaging have improved diagnosis and prognosis,
      whereas developments in interventional neuroradiology have extended the range of
      therapy to different patient populations. These changes in service demand the
      identification of those clinical and technical factors distinguishing feasibility
      from futility, in order to increase population efficiency and reduce the harm
      associated with inappropriate therapy.

PMID- 17016246
TI  - Is anticoagulation and central neural blockade a safe combination?
AB  - The indiscriminate insertion of epidural or subarachnoidal needles or catheters
      in patients who are anticoagulated or are about to be anticoagulated carries the
      inherent risk of the potential development of a compressing vertebral canal
      haematoma, which may severely jeopardize the patient's (quality of) life.
      Although the isolated use of aspirin or non-steroidal anti-inflammatory drugs in
      general is no longer considered a problem, its combination with any form of
      heparin therapy is. Intraoperative heparinization during cardiac or vascular
      surgery can be safely performed provided a minimum time interval between the
      regional anaesthetic block and the subsequent heparinization is respected and
      indwelling catheters are removed after the disappearance of any remaining heparin
      effect. Similarly, central neural blockade in combination with the
      thromboprophylactic use of standard unfractionated heparin or low-molecular
      weight heparins is possible if: (1) only thromboprophylactic heparin doses are
      used; and (2) a specific minimum time interval between the previous or the next
      dose of the anticoagulant and the initiation of the block or the removal of the
      indwelling catheter is observed.

PMID- 17016247
TI  - Does regional anesthesia improve outcome after surgery?
AB  - The benefits and complications associated with regional anesthesia are assessed
      on the basis of a review of the recent literature. Benefits are separately
      considered as: (1) effects on hospital discharge; (2) effects on pulmonary
      function; (3) cardiac benefits; (4) effects on ambulation; (5) effects on
      metabolic stress responses; and (6) the preemptive effect. Complications reviewed
      are those of recent interest, and include epidural hematoma in association with
      anticoagulant therapy, and neural toxicity in association with high-dose local
      anesthetic.

PMID- 17016248
TI  - New drugs for neuraxial blockade.
AB  - Recent years have seen a dramatic increase in the number of agents used for
      neuraxial blockade. Together with the developments in local anaesthetics and
      opioids, completely new categories of agents have been investigated for
      intrathecal and epidural use. A review of the recent literature reveals the
      potential for improvement in achieving balanced anaesthesia and analgesia, in
      particular combining agents to reduce adverse effects.

PMID- 17016249
TI  - Toxicity of spinal local anaesthetics.
AB  - Recent reports of severe neurological injury after spinal anaesthesia have
      generated concerns about the neurotoxic potential of local anaesthetics and, in
      particular, of lignocaine. Further, there is an increasing body of evidence
      indicating that transient neurological symptoms commonly occur after uneventful
      lignocaine spinal anaesthesia but not after bupivacaine. Results from an
      epidemiological study suggest that patient positioning and outpatient status are
      major co-factors. Neither the dose nor the concentration of lignocaine appear to
      reduce the risk for transient neurological symptoms. Available data on
      alternative short-acting local anaesthetics with respect to transient
      neurological symptoms are limited and conflicting. Experimental data provide
      further information on factors contributing to local anaesthetic induced
      neurotoxicity: adrenaline significantly increases the neurotoxic effects of
      lignocaine in vivo, whereas the addition of glucose does not.

PMID- 17016250
TI  - Surveys on the use of regional anaesthesia in obstetrics.
AB  - Regional anaesthetic techniques in obstetrics have gained more and more
      importance during the last few years. Several surveys published recently show a
      remarkable increase in caesarean sections performed under regional anaesthesia,
      in many countries. Furthermore, epidural analgesia has proved to be one of the
      most effective methods of pain relief during vaginal delivery. Especially in
      patients at risk of an abdominal delivery, an epidural catheter already in place
      during labour can be used for consecutive caesarean section without delay and is
      used as a strong argument in favour of epidural anaesthesia. This article gives
      an overview of recent surveys of regional anaesthesia in obstetrics.

PMID- 17016251
TI  - Infectious complications of epidural anaesthesia and analgesia.
AB  - Clinically overt infections of the epidural catheter skin entry site occur in
      approximately 5% of patients after a few days; deep catheter tract infections
      occur in approximately 5% of patients after more prolonged epidural analgesia.
      This indicates that potentially serious epidural infectious complications are
      ever-present risks of epidural anaesthesia and analgesia. This review focuses on
      risk factors and guidelines for routine epidural analgesia that may minimize the
      risks of serious infectious complications.

PMID- 17016253
TI  - Imaging of pain: recent developments.
AB  - Brain imaging of pain has made remarkable strides in the past year and a half.
      The basic regional activation pattern after acute nociceptive stimulation is now
      fairly well clarified. The extension of imaging studies from normal subjects to
      include cohorts of pathological pain patients is occurring. The techniques of
      positron emission tomography, functional magnetic resonance imaging and single
      photon emission computed tomography have all been applied to the study of human
      pain processing and the assessment of physiological interventions or
      psychological manipulations. Studies using labelled ligands to trace receptor
      alterations have also been conducted. Although more work could be done on the
      pharmacology and physiology of anesthesiology, the resulting set of observations
      provides a deeper understanding of the basic human neurophysiology of pain and a
      potential neural framework for better pain management.

PMID- 17016254
TI  - Gender differences in pain.
AB  - A literature survey reveals clear evidence of sex differences in the incidence of
      painful conditions and their severity, both being greater in women. The possible
      causes of this sexual dimorphism are discussed. Sex-role stereotyping may be
      relevant and there is evidence to indicate that, perhaps through their roles as
      carers, women seek and utilize more medical services than men. Less clear-cut
      evidence for anatomical and physiological differences is reviewed, together with
      documentation of hormonal (and reproductive cycle) influences on the operation of
      those systems.

PMID- 17016255
TI  - The analgesic potential of compounds acting at acetylcholine receptors.
AB  - Compounds acting at both nicotinic and muscarinic acetylcholine receptors appear
      to have antinociceptive activity, and acetylcholine release in the spinal cord
      may be involved in endogenous pain control. The therapeutic potential of most
      cholinergic agonists or of agents that increase synaptic acetylcholine is limited
      by side effect liabilities. Recent studies, however, have identified some
      compounds with improved safety profiles. Multiple subtypes of nicotinic and
      muscarinic receptors exist, and molecular and pharmacological studies are just
      beginning to identify which subtypes are involved in the antinociceptive effects
      of cholinergic receptor activation. Further advances in this area will be
      necessary to determine if the rational design of subtype selective cholinergic
      agonists will provide novel analgesic agents.

PMID- 17016256
TI  - Peripheral opioid analgesia: from experimental to clinical studies.
AB  - Previous experimental findings demonstrating that the local administration of
      opioids produces dose-dependent and naloxone-reversible analgesic effects, which
      are restricted to the periphery, have now been confirmed in clinical studies.
      Accordingly, opioid receptors have been identified on peripheral sensory neurons
      of animals and humans. In addition to their efficacy in somatic pain, peripheral
      opioids potently inhibit visceral pain. These effects are enhanced under
      inflammatory conditions. Initial clinical trials have now examined local opioid
      effects in chronic inflammatory states such as arthritis. They demonstrated
      surprisingly long-lasting analgesic effects, probably caused by additional anti
      inflammatory effects. The introduction of a new generation of opioids that act
      selectively in the periphery may open a novel approach to treating pain
      effectively without undesirable central side-effects such as respiratory
      depression and addiction.

PMID- 17016257
TI  - Opioid analgesia: new information from gene knockout studies.
AB  - The cloning of opioid peptides and receptors has led to the development of
      knockout mice deficient in a gene encoding for each peptide and each receptor.
      The major advantage of the knockout approach is the complete selectivity that the
      removal of a protein encoded for by a gene provides. These knockout animals are
      adding to our knowledge of the physiology, pathophysiology and pharmacology of
      opioid systems. In addition, they are providing real impact in addressing the
      long-standing debates over receptor subtype heterogeneity and functional
      cooperativity between receptor subtypes.

PMID- 17016258
TI  - Current world literature.

PMID- 17016260
TI  - Recent developments in regional anesthesia for ambulatory surgery.
AB  - The use of regional anesthesia techniques is increasing in popularity because
      they reduce the incidence of postoperative complications, including nausea,
      vomiting, and pain, and decrease the recovery time and hospital stay. This
      article reviews the recent developments in regional anesthesia techniques and the
      modifications necessary to adapt them for ambulatory surgery.

PMID- 17016261
TI  - Management of the paediatric patient.
AB  - Recent introduction of new fast-onset short-duration anaesthetic drugs and the
      use of regional anaesthesia techniques in children have resulted in good control
      of anaesthesia and perioperative pain with few adverse effects. Ambulatory
      surgery has gained popularity in paediatric practice, particularly as children
      are often otherwise healthy and usually undergo minor surgery.

PMID- 17016262
TI  - Postoperative nausea and vomiting.
AB  - Worldwide, approximately 80-100 million surgical procedures are performed under
      general anaesthesia each year. Despite major advances in surgical techniques and
      the introduction of new anaesthetic agents with reduced emetogenicity, the
      incidence of postoperative nausea and vomiting (20-30%) has remained largely
      unchanged over the past few decades. Postoperative nausea and vomiting are of
      greatest concern after ambulatory surgical procedures because they may delay
      discharge and result in unanticipated hospital admission, thus increasing the
      cost of the procedure by a large margin. This review discusses the current status
      of the antiemetic therapy of postoperative nausea and vomiting.

PMID- 17016263
TI  - Postanaesthetic considerations and complications after ambulatory anaesthesia.
AB  - Ambulatory or day-case surgery is being employed to an ever-increasing extent.
      Although it has many advantages, it is not suited to the needs of every patient.
      For example, patients who live alone, particularly the elderly, might well not be
      able to care for themselves adequately after such surgery and are probably at a
      higher risk of developing complications, including infections. Furthermore, pain
      treatment may be insufficient, as a consequence of which recovery can be
      prolonged and the resumption of normal daily activities might be delayed. Nausea,
      dizziness and vomiting can also prolong recovery and need to be adequately
      treated after ambulatory surgery. Therefore, the often cited cost effectiveness
      of ambulatory surgery is questionable if complications cannot be prevented or
      treated effectively.

PMID- 17016264
TI  - Airway management.
AB  - The last decade of the millennium has witnessed the introduction of new
      extratracheal airway devices for use in fasted patients undergoing ambulatory
      anaesthesia. A growing awareness of the potential of such devices in the
      difficult airway has contributed to their increasing use.

PMID- 17016266
TI  - Assessment of clinical competence.
AB  - Despite endless efforts in the quest for credible methods for evaluating clinical
      competence, the objective remains elusive. The components of competence include
      both clinical (interview skills, physical examination, differential diagnosis and
      therapeutic modalities) and technical skills. Written and oral examinations and,
      more recently, objective structured clinical examinations have been used as
      instruments for assessing the progress of trainees as well as for college or
      board certification and licensure to practice medicine. The American Board of
      Anesthesiology has adopted a more rigorous process for evaluating residents in
      training (Certificates of Clinical Competence). Newer methods have attempted to
      measure the competence of practicing physicians, including the analysis of data
      from physician-submitted 'report cards', 're-certification' examinations, and
      patient outcome studies. Whole-body computerized patient simulators have become a
      major area of research for teaching clinical skills and assessing behavior as
      well as patient management during critical incidents. This review examines the
      significant literature in each of the areas cited.

PMID- 17016267
TI  - Training in intensive care medicine: should it be an integral part of
      anaesthesiology training?
AB  - As the action around a patient with failing vital functions is getting more
      multidisciplinary, there seems to be a developing consensus that intensive care
      medicine is not going to be regarded as a specialty in its own right. Before
      becoming board certified in intensive care medicine a board certification in a
      primary specialty will be required. Anaesthesiological expertise and skills will
      continue to be important, even in intensive care medicine of the future. It is
      the level of broad medical knowledge, clinical capability and scientific
      competence that will decide the future leadership of this multi-discipline.

PMID- 17016268
TI  - Continuous professional development for anaesthetists.
AB  - Anaesthesia, as well as the whole of medicine, is involved in a revolution not
      only technical but also economic, because of the need for cost-containment in
      healthcare delivery. Continuing medical education, primarily devoted to updating
      knowledge and skills, is moving rapidly towards continuous professional
      development. A permanent evolution of practitioners is mandatory in order that
      they are able to adapt their practice to technical, ethical and economic changes,
      integrated in a team-working and multidisciplinary approach to patient care.

PMID- 17016269
TI  - What is the future of advanced trauma life support training?
AB  - Within the past 20 years, advanced trauma life support has developed from a
      regional to an international educational programme, with 31 participating
      countries. Notwithstanding the general acknowledgement of the effectiveness of
      advanced trauma life support procedures for improving early hospital trauma
      management and the specific knowledge and skills of participants, some criticism
      has come from the community of British anaesthetists, regarding course contents,
      the possibility of participating, the significance of skills for trained
      anaesthetists, team-related concerns and, of course, costs. Now that we have 10
      years' experience from European advanced trauma life support courses, we want to
      take the opportunity to assess the advantages and possible deficiencies of this
      programme.

PMID- 17016271
TI  - Current world literature.

PMID- 17016270
TI  - Percutaneous tracheostomy in the intensive care unit.
AB  - Percutaneous tracheostomy is now established in intensive care practice. However,
      discussion continues on many aspects of the procedure. This update reviews recent
      studies of bedside percutaneous tracheostomy, which suggest that the commonly
      used techniques are safe in terms of short and long-term complications. The
      introduction of percutaneous tracheostomy into an intensive care unit has
      training implications, particularly for surgeons. The timing of percutaneous
      tracheostomy in critically ill patients, and the use of the technique in children
      remain controversial.

PMID- 17016272
TI  - Perioperative myocardial cell injury in noncardiac surgery--time for an
      optimistic view?

PMID- 17016273
TI  - Cardiovascular pharmacology: new drugs and new indications.
AB  - This review presents a brief overview of some of the many exciting developments
      that are taking place in the field of cardiovascular pharmacology. Research
      continues to progress at a rapid rate, and we can expect many drugs to enter the
      clinical arena within the next few years. It must be borne in mind, however, that
      the pharmaceutical industry and hospital budgetary restrictions sometimes limit
      drug development and occasionally interrupt clinical trials, even before their
      results have been obtained.

PMID- 17016274
TI  - Cerebral dysfunction after cardiac surgery--are we moving forward?
AB  - This review focuses on the effects of cardiac surgery and cardiopulmonary bypass
      on the brain, with special emphasis on the results of recently conducted studies.
      The incidence of postoperative neurological and neuropsychological deficits and
      risk factors for cerebral injury are reviewed. The relationships between cerebral
      embolic load, release of biochemical markers of brain injury and cognitive
      dysfunction after cardiac surgery are also reviewed. Finally, recently gained
      information on the management of cardiopulmonary bypass is discussed, along with
      the results of recent pharmacological neuroprotective trials in patients
      undergoing cardiac surgery.

PMID- 17016275
TI  - Transesophageal echocardiography.
AB  - Anesthesiologists are increasingly using transesophageal echocardiography in both
      cardiac and noncardiac cases. In cardiac anesthesia, considerable progress has
      been made in the evaluation of mitral valvular disease. Transesophageal
      echocardiography has also become more useful in the hemodynamic evaluation of
      patients undergoing coronary artery bypass grafting. It is particularly valuable
      in minimally invasive surgery and in heart surgery to correct congenital defects.

PMID- 17016276
TI  - Cardiac surgery and the coagulation system.
AB  - This review focuses on the activation of the haemostatic system during
      cardiopulmonary bypass. The interaction of different cascade systems are
      examined, in particular the relation of inflammation with haemostasis. Novel
      strategies to supplement or replace heparin for anticoagulation during
      cardiopulmonary bypass have recently been described. Drug approaches to reduce
      activation of haemostasis reported during the review period are already well
      established. Their influence on the inflammatory response may offer interesting
      perspectives for the future.

PMID- 17016277
TI  - Ischemic preconditioning, myocardial stunning and anesthesia.
AB  - Brief periods of ischemia have been shown to protect the heart against a
      subsequent prolonged ischemic insult, a phenomenon known as ischemic
      preconditioning. The protective effects of preconditioning markedly reduce
      myocardial ischemic injury in vivo. Volatile anesthetics have been shown to
      protect myocardium against infarction by a mechanism similar to that of ischemic
      preconditioning. Contractile dysfunction occurs after a brief period of
      myocardial ischemia, despite restoration of coronary blood flow in the absence of
      tissue necrosis. This process is known as myocardial stunning and has important
      clinical ramifications. Evidence indicates that adenosine triphosphate-regulated
      potassium channel function plays a central role in ischemic preconditioning,
      stunned myocardium, and in anesthetic-induced protection against ischemic injury.

PMID- 17016278
TI  - Video-assisted thoracoscopic surgery.
AB  - Video-assisted thoracoscopic surgery is finding an ever-increasing role in the
      diagnosis and treatment of a wide range of thoracic disorders that previously
      required sternotomy or open thoracotomy. The potential advantages of video
      assisted thoracoscopic surgery include less postoperative pain, fewer operative
      complications, shortened hospital stay and reduced costs. The following review
      examines the surgical and anesthetic considerations of video-assisted
      thoracoscopic surgery, with an emphasis on recently published articles.

PMID- 17016279
TI  - Pulmonary function after cardiac and thoracic surgery.
AB  - Cardiac and thoracic surgery cause alterations in ventilatory function that can
      lead to significant postoperative pulmonary complications. These complications
      often occur among patients with pre-existing pulmonary dysfunction and cause
      significantly longer hospital stays. This review explores some of the recent
      literature concerning this issue, including the effects of lung reduction
      surgery.

PMID- 17016280
TI  - Pulmonary transplantation.
AB  - Anesthetic technique for pulmonary transplantation varies with recipient's
      underlying lung disease, procedure performed and regional practice. The pulmonary
      allograft is vulnerable to mechanical and biochemical injury throughout the
      harvesting, preservation and engraftment procedures. Mechanisms of allograft
      injury are reviewed, with suggestions for incorporation of strategies to minimize
      injury into clinical practice. Particular emphasis is placed on the use of nitric
      oxide for treatment of reperfusion injury.

PMID- 17016281
TI  - Current status of lung volume reduction.
AB  - Lung volume reduction surgery, where 20-30% of lung is resected in patients with
      end-stage emphysema, has been shown in a number of published series to improve
      expiratory lung volumes, exercise capacity, and subjective well being. This
      procedure, originally described in the early 1950s, has caught the imagination of
      the public and medical fraternity. This operation may find utility as an
      alternative to lung transplantation. Only when the results of a number of
      randomized clinical trials are available, however, will an assessment of the true
      value of this procedure be known.

PMID- 17016282
TI  - Anesthetic considerations for thoracic neurosurgical procedures.
AB  - Anesthetic considerations for thoracic and thoracoscopic neurosurgical procedures
      are considered, emphasizing the need to provide anesthetic stability during
      prolonged periods of one-lung ventilation, while optimizing conditions for
      intraoperative monitoring of spinal cord integrity.

PMID- 17016283
TI  - Bibliography. Current world literature. Cardiovascular anesthesia.

PMID- 17016284
TI  - Euthyroid sick syndrome.

PMID- 17016285
TI  - Neuromuscular dysfunction in critical illness: what are we dealing with?
AB  - Neuromuscular weakness is a very common and debilitating problem for survivors of
      critical illness. Neurophysiological abnormalities are almost ubiquitous in these
      patients, and often favour a diagnosis of axonal polyneuropathy, whereas muscle
      histology, where available, reveals a high incidence of atrophy and necrosis. The
      precise nature and aetiology of this complex disorder is not yet well understood.

PMID- 17016286
TI  - Adrenal dysfunction in critical illness: a clinical entity that requires
      treatment?
AB  - Corticosteroids are of key importance in controlling the immune system and in the
      maintenance of cardiovascular function. Thus, an adequate function of the adrenal
      cortex is essential for survival in critical illness. There is growing evidence
      that adrenocortical function can become impaired during critical illness, because
      of deleterious effects of cytokines, leading to a state of relative adrenal
      dysfunction. Under these circumstances, administration of corticosteroids is
      necessary for recovery of the patient. How such a state of adrenal dysfunction
      should be detected is still not clear, however, making it difficult to decide
      when to administer corticosteroids and to which patients.

PMID- 17016287
TI  - New perspectives for prevention/treatment of acute renal failure.
AB  - Acute renal failure continues to be a difficult clinical problem in critically
      ill patients, despite advances in critical care and dialysis. This review focuses
      on some of the current issues in the nondialytic and dialytic management of these
      patients. Critical analysis of some still frequently used drugs in these patients
      such as diuretics and dopamine in so-called 'renal doses' has revealed little
      beneficial effect. Recent data are in conflict with previous suggestions that
      biocompatible membranes have a positive effect on the recovery of renal function
      and on patient mortality. The choice between intermittent haemodialysis and
      continuous renal replacement therapy should be made on an individual basis and
      not on the basis of 'dogmatic' opinion.

PMID- 17016288
TI  - Acute liver failure.
AB  - Worldwide, viral infection is responsible for the majority of cases of acute
      liver failure, and the presence of co-existing chronic viral hepatitis may
      increase its severity. The newly described hepatotrophic viruses, hepatitis G
      virus and transfusion-transmitted virus, are unlikely to be major aetiological
      agents. In the USA and western Europe drug-induced hepatotoxicity is the most
      common cause, and most frequently results from acetaminophen. Hepatotoxicity
      caused by Ecstasy is increasingly important, particularly in young adults.
      Hepatic encephalopathy and cerebral oedema remain important and life-threatening
      complications, and their pathogenesis is not completely understood. The effects
      of the cerebral metabolism of the high levels of ammonia that circulate in
      hepatic failure appear to be important. Induced hypothermia is a promising
      modality of treatment for refractory cerebral oedema, but the only form of
      treatment known to improve survival is emergency liver transplantation. Living
      donor and auxiliary liver transplantation are likely to improve survival rates
      further and reduce the number of patients requiring long-term post-transplant
      immunosuppression.

PMID- 17016289
TI  - Transfusion in the intensive care unit: strategies under scrutiny.
AB  - The transfusion of blood products continues to be an important technique for
      resuscitating patients in intensive care settings. A number of provocative
      studies have been published in the past year which examine the transfusion of
      blood products and alternatives. The Transfusion Requirements in Critical Care
      (TRICC) trial clearly established the safety of a restrictive transfusion
      strategy, thereby suggesting that physicians could easily minimize exposure to
      allogeneic red blood cells by lowering their transfusion threshold. The
      crystalloids versus colloids debate was also fueled by a number of studies this
      past year, specifically a meta-analysis which reported a 4% increase in absolute
      risk of mortality associated with resuscitation therapy using colloids. A recent
      study demonstrated that erythropoietin is a promising therapy in the intensive
      care. We can anticipate the results of a trial, currently underway, for further
      evidence of the use of smaller doses of erythropoietin in the ICU setting.

PMID- 17016290
TI  - Clinical trials in sepsis: an update.
AB  - In this article, we place clinical sepsis trials from the past year in the
      context of similar sepsis trials run over the past three decades. These recent
      clinical sepsis trials include studies of agents administered to limit the
      effects of specific host proinflammatory mediators (tumor necrosis factor,
      platelet-activating factor and prostaglandins), studies of use of corticosteroids
      at low doses late in sepsis, and studies of administration of high doses of a
      nonspecific nitric oxide synthase inhibitor to decrease nitric oxide production
      in septic shock. The three trials of agents designed to limit host
      proinflammatory mediators showed minimal beneficial effects, results that are
      similar to those of the approximately 20 previous trials of similar agents. Low
      dose corticosteroid therapy reversed shock and showed nonsignificant trends
      towards improvements in survival rates. In contrast, high doses of
      corticosteroids given early in sepsis have shown harmful effects in clinical
      sepsis trials. Finally, inhibition of nitric oxide production was lethal,
      indicating that high doses of nonspecific inhibitors of nitric oxide production
      are contraindicated in septic shock.

PMID- 17016291
TI  - Challenges for trauma anesthesia in the new millennium.

PMID- 17016292
TI  - Modern airway management for the trauma patient.
AB  - Over the last decade there has been significant advancement in airway management
      and a recent closed claims analysis indicates a decrease in claims since the
      1980s. Studies and new airway devices have focused on managing the difficult
      airway and the failed intubation, problems which are common to the trauma
      patient. Although new airway devices have improved our ability to ventilate these
      patients, they are not 100% reliable nor do they provide a definitive airway.
      Formal training in airway management and the use of these airway devices has much
      room for improvement. With increased emphasis on training and the development of
      improved intubating aids, modern management of the difficult airway may approach
      100% success.

PMID- 17016293
TI  - Anaesthetic care of the injured child.
AB  - Paediatric trauma care is complex and diverse. Paediatric trauma care systems
      have proven difficult to evaluate, and further work is required to assess their
      usefulness. Furthermore, head injury is a major component of paediatric trauma
      and its management is becoming increasingly multifactorial. As its
      pathophysiology continues to unfold there is much opportunity for ongoing
      research in this area.

PMID- 17016294
TI  - End-points of resuscitation how much is enough?
AB  - Fluid resuscitation after traumatic hemorrhage has historically been instituted
      as soon after injury as possible. Patients suffering from hemorrhagic shock may
      receive several liters of crystalloid, in addition to colloid solutions, in an
      attempt to normalize blood pressure, heart rate, urine output, and mental status,
      which are the traditional end-points of resuscitation. Current theory and recent
      investigations have questioned this dogma. Resuscitation goals may be different
      between when the patient is actively hemorrhaging, and once bleeding has been
      controlled. Newer markers of tissue and organ system perfusion may allow a more
      precise determination of adequate resuscitation.

PMID- 17016295
TI  - Improving outcome for the injured brain and spinal cord.
AB  - Although injury to the brain and spinal cord can have varied etiology and
      mechanisms, the common pathway appears to be mediated by occurrence of ischemia
      and secondary injury. Because the pathophysiology in traumatic brain injury is
      heterogeneous, improvement in outcome will come from better diagnosis and
      monitoring, so that targeted therapy can be tailored to the individual patient.
      This review focuses on traumatic injury to the brain and spinal cord, and
      highlights recent developments in this area.

PMID- 17016296
TI  - Awareness and different forms of memory in trauma anaesthesia.
AB  - Awareness during surgery and memory for perioperative events may have substantial
      psychological consequences for the patient. The risk of awareness during trauma
      surgery is higher than during most elective procedures due to the fact that
      administration of adequate concentrations of anaesthetics is not always feasible.
      As a consequence, the risk of memory formation might be increased. The present
      review discusses different forms of memory, and the possibilities and limitations
      of awareness and memory prevention.

PMID- 17016297
TI  - Avoiding hypothermia in the trauma patient.
AB  - Hypothermia may be encountered during the management of severely injured
      patients, and with exception of deliberate hypothermia for neuroprotection, has
      been associated with increased morbidity and mortality. This review examines the
      recent literature with regard to risk factors for developing hypothermia,
      significance of hypothermia, therapeutic use of hypothermia, and invasive and
      noninvasive methods to prevent and treat hypothermia.

PMID- 17016298
TI  - Prehospital trauma care.
AB  - Concepts regarding uniform reporting of data after trauma and regarding treatment
      of brain trauma patients at the scene have recently been agreed upon in consensus
      processes. Endotracheal intubation and alternatives are as controversially
      discussed as fluid resuscitation and helicopter transport of trauma victims. Long
      term outcomes of trauma patients should more frequently be studied using the
      Quality of Wellbeing Scale.

PMID- 17016299
TI  - Reducing post-traumatic morbidity with pain management.
AB  - Since significant pain can adversely affect multiple organ systems, many
      anesthesiologists believe that effective pain control can decrease perioperative
      and post-trauma morbidity. To achieve the goal of attenuating the physiological
      stress response associated with trauma, modalities such as patient-controlled
      analgesia, epidural infusions and peripheral nerve blocks are being utilized.
      This article will review the physiological response to pain, the new strategies
      and techniques for providing pain relief, and recent literature that evaluates
      the effect of the newer pain modalities on perioperative morbidity.

PMID- 17016300
TI  - We need an ethical imperative for physicians to treat pain optimally.

PMID- 17016301
TI  - Scientific journals with editorial independence: an endangered species?
AB  - Editorial freedom is one essential component in guaranteeing honesty and
      integrity in the standards of publishing scientific material. Two recent
      episodes, in which editors of leading weekly general medical journals have been
      removed from office by editorial management boards, represent a direct assault on
      this concept. These events, in combination with many other pervasive and
      traducing influences, especially of a commercial and financial nature, imply that
      editorial freedom cannot be guaranteed, even in medical and scientific
      publishing.

PMID- 17016302
TI  - Perioperative do-not-resuscitate orders.
AB  - Recent advances in perioperative refusal of resuscitation center on goal-directed
      orders. Goal-directed orders permit patients to define perioperative
      resuscitation in terms of outcomes rather than procedures. A typical goal
      directed order may state 'The patient desires resuscitative efforts during
      surgery and in the postoperative care unit only if the adverse events are
      believed to be both temporary and reversible, in the clinical judgment of the
      attending anesthesiologists and surgeons.' This review also discusses ways to use
      the ability to withdraw care as a way of honoring patients' wishes.

PMID- 17016303
TI  - Are institutional review boards effective in safeguarding patients in intensive
      care units?
AB  - Institutional Review Boards have been recently audited in the US, and a great
      deal of concerns and criticisms appeared in the medical literature and the lay
      press. Globally, these comments questioned the efficiency of Institutional Review
      Boards in fulfilling their basic mission, the protection of patients subjected to
      biomedical research. Vulnerable populations, such as psychiatric and incompetent
      patients, were particularly identified. In intensive care units, conducting
      research in critically ill patients unable to give informed consent themselves
      remains a hot issue. Several possibilities have been proposed and assessed in the
      recent past: pre-emptive (global) consent, proxy consent from a surrogate,
      deferred consent, and, more recently, waiver of consent for emergency research.
      Obviously, the inability to deal with this major obstacle (i.e. obtaining consent
      from incompetent patients) would lead to the cessation of any research in
      intensive care units, which is hardly acceptable and certainly unethical. Recent
      published studies have reported over-mortality in treatment groups, posing new
      questions: who should be informed of those failures, and when? What is the role
      of Institutional Review Boards in preventing such an issue? What type of
      indemnity should be proposed to the family of deceased patients during a trial?

PMID- 17016304
TI  - Severity scoring systems and the prediction of outcome from intensive care.
AB  - Severity scoring systems are tools that provide a predicted mortality for a group
      of intensive care unit patients on the basis of derangement of their physiology
      and some past medical history. This predicted mortality can then be compared with
      the actual mortality to give some indicator of the effectiveness of the package
      of care delivered by the intensive care unit, corrected for differences in case
      mix. Thus, their primary use is in audit, and they are designed for use on large
      populations of patients and not on individuals. In spite of a large number of
      publications on the development, refinement and testing of scoring systems,
      papers describing their use in comparative audit are very rare. This may be
      partly due to limitations in their ability to predict mortality outside the
      population on which they were developed, and to the change in calibration of the
      system with time and advances in medical science. This review briefly addresses
      the limitations of severity scoring systems in light of recent publications.

PMID- 17016305
TI  - Effect of perioperative evaluation and consultation on cost and outcome of
      surgical care.
AB  - The preoperative evaluation has traditionally focused on identifying the subset
      of patients for whom further testing would identify patients at increased risk.
      The past decade has seen a reorientation to focus on developing systems, both
      guidelines and preoperative evaluation clinics, that can reduce the number of
      unindicated testing and more appropriately direct the preoperative evaluation as
      a means of reducing costs. In patients who are at risk for cardiac disease
      administrative data-sets have been used to link perioperative interventions with
      outcome. Future research must be directed at proving effectiveness in randomized
      clinical trials.

PMID- 17016306
TI  - Is pulmonary aspiration still an important problem in anesthesia?
AB  - Recent studies suggest that perioperative pulmonary aspiration is an infrequent
      event (approximately 1 : 2000-3000 general anesthetics), but its impact on
      individual patients can be devastating. Patients who appear to have the greatest
      risk of developing severe pulmonary morbidity or dying after aspiration are those
      who are sick (American Society of Anesthesiologists physical classification 3 or
      greater) and elderly. As a general rule, children have less morbidity from
      pulmonary aspiration.

PMID- 17016308
TI  - Is blood pressure the best parameter to evaluate volume preload in obstetric
      anaesthesia?

PMID- 17016307
TI  - Bibliography. Current world literature. Intensive care.

PMID- 17016309
TI  - Patient-controlled epidural analgesia or continuous infusion: advantages and
      disadvantages of different modes of delivering epidural analgesia for labour.
AB  - Patient-controlled epidural analgesia, intermittent top-up and continuous
      infusion are equally effective in providing epidural pain relief during labour.
      Patient-controlled epidural analgesia is associated with a significant reduction
      in hourly dose requirements when compared with continuous infusion, and by
      transferring the responsibility for epidural top-up, it offers the parturient the
      psychological benefit of being in control. For these reasons, patient-controlled
      epidural analgesia may become the method of choice for epidural pain relief
      during labour. However, the safety of the method needs to be documented more
      extensively, and the advantage of a reduction in hourly dose requirements needs
      to be visualized in terms of an improvement in labour or neonatal outcome.
      Moreover, the optimal dose, drug combination and settings still remain to be
      determined.

PMID- 17016310
TI  - Epidural analgesia during labor and maternal fever.
AB  - Most studies indicate that epidural analgesia during labor is associated with
      maternal fever, although the nature of this fever is unclear. The consequences of
      maternal fever may include increased neonatal evaluations for sepsis, the
      increased use of antibiotics, and prolonged hospital stay. However, the need for
      such measures after epidural analgesia during labor is controversial. This
      article discusses currently held views on this issue.

PMID- 17016311
TI  - Acid aspiration prophylaxis and caesarean section.
AB  - Acid aspiration syndrome still contributes to the few anaesthesia-related deaths
      in caesarean section. Although none of the numerous measures intended to prevent
      such fatalities is based on clear evidence, many different regimens are being
      used. As obstetric acid aspiration syndrome occurs mainly in general anaesthesia,
      using regional techniques wherever possible may be the most effective
      prophylactic measure.

PMID- 17016312
TI  - What is the best way to provide postoperative pain therapy after caesarean
      section?
AB  - In the following text recently published data on postoperative pain therapy after
      caesarean section will be summarized. As most papers discuss epidural and
      intrathecal strategies of pain relief, these aspects of pain therapy for the
      often underestimated pain after caesarean section will be emphasized.

PMID- 17016313
TI  - Remifentanil for gynaecological and obstetric procedures.
AB  - Recently, with the introduction of the novel mu-opioid receptor agonist
      remifentanil, anaesthesiologists have acquired a unique tool to provide adequate,
      titratable and predictable analgesia throughout surgery, without the risk of
      opioid-related delay in postoperative recovery. This new compound will therefore
      mandate a change in anaesthesia practice from opioid-restricted to opioid
      dominated anaesthesia. It is the first in the class of esterase-metabolized
      opioids within the 4-anilidopiperidine series of drugs, and it possesses an
      analgesic potency similar to that of fentanyl. The advantages of remifentanil are
      mainly related to its unique pharmacokinetics, whereas its pharmacodynamics are
      the same as those of fentanyl. Because of these characteristics, remifentanil
      based anaesthesia allows profound opioid analgesia intraoperatively, with rapid
      and predictable awakening thereafter. Review of the recent literature reveals the
      potential of remifentanil for improving analgesia in gynaecological procedures
      and its theoretical advantage in obstetric procedures.

PMID- 17016314
TI  - Fetal surgery: general or regional anaesthesia?
AB  - Major improvements in the diagnosis and treatment of fetal malformations,
      including in-utero surgical repair, have occurred in the past decade. As opposed
      to anaesthesia for caesarean sections, a high placental drug transfer is
      warranted to provide adequate fetal anaesthesia and immobility, strongly
      favouring the use of general anaesthesia for these cases. Even though the
      question of fetal pain perception is still debated, studies suggest that
      attenuation of the fetal stress response can improve outcome. Other major
      concerns include the maintenance of uterine blood flow and uterine relaxation, as
      premature labour and delivery severely limit fetal benefits from surgery. When
      performing these procedures, physicians have a special responsibility to weigh
      maternal risks against fetal benefits and should not jeopardize the life of the
      mother for procedures with questionable fetal outcome.

PMID- 17016315
TI  - Anaesthetic management of paediatric patients: further steps towards excellence.

PMID- 17016316
TI  - Postoperative pain management in infants and children: new developments.
AB  - The elimination of pain should be of outstanding importance for all people caring
      for children. A concept of balanced analgesia including non-steroidal anti
      inflammatory drugs, opioids and local anaesthetics is widely accepted. This
      review focuses on extending analgesia beyond the immediate postoperative period,
      the understanding of pharmacokinetic-pharmacodynamic interactions of paracetamol,
      the side-effects of opioids during patient-controlled administration, and the
      position of ropivacaine in paediatric pain management. For the majority of
      clinical situations, however, we already have established and functioning
      concepts for analgesia; we only have to use them!

PMID- 17016317
TI  - Pulmonary aspiration and lung injury.
AB  - Lung injury after aspiration, although very rare, is a feared and potentially
      devastating sequela after anaesthesia. This paper summarizes the most recent
      studies in aspiration lung injury focusing on its clinical epidemiology, new
      insights in its pathophysiology and innovative concepts in its prevention and
      therapy.

PMID- 17016318
TI  - Ketamine: new uses for an old drug.
AB  - Over the years, ketamine has found many applications in paediatric
      anaesthesiology. Recent insights into the mechanism of its central action, and
      the pharmacology of its isomers have led to a re-evaluation of this drug,
      expanding the range of indications in adults. The best examples of the uses of
      ketamine as an analgesic are: in brief diagnostic or therapeutic procedures,
      during the post-operative period in neonates and infants as well as in paediatric
      anaesthesia and intensive care.

PMID- 17016319
TI  - Autotransfusion and blood-sparing techniques in infants and children.
AB  - While several techniques to reduce perioperative blood loss have been established
      for surgery in adults, not all of them are applicable in paediatric surgery.
      Further, far less is known about the efficacy of these techniques in this
      specific population. Consequently, techniques for the prevention of blood loss
      are often neglected. However, it is these young patients, with their remaining
      life expectancy, who will benefit the most from any prevented infection (HIV,
      hepatitis, etc.) or from any immunological complications. Hemodilution is limited
      because of the high percentage of fetal hemoglobin in small infants, as well as
      the additional anaesthetic needed to obtain blood. Until recently, intraoperative
      autotransfusion was ineffective in small children due to technical limitations;
      however, advanced technology now renders intraoperative autotransfusion possible,
      even in infants weighing less than 20 kg.

PMID- 17016320
TI  - Non-invasive aortic blood flow measurement.
AB  - Invasive monitoring is rarely used for children undergoing routine anaesthesia,
      whereas usual non-invasive haemodynamic measurements such as heart rate and blood
      pressure monitoring are unable to detect cardiovascular changes rapidly and
      precisely. In contrast, oesophageal aortic blood flow echo-Doppler is an easy,
      non-invasive and accurate method to monitor cardiac performance properly and
      continuously. Therefore, it could represent a useful addition to peri-anaesthetic
      monitoring techniques, particularly in infants and small children.

PMID- 17016321
TI  - Paediatric perioperative anaesthesia environment.
AB  - This paper reviews the primary guidelines for management of the paediatric
      perioperative anaesthesia environment. The role of environment is defined in the
      different preventive strategies to improve quality of paediatric anaesthesia
      (i.e. decrease in perioperative complications due to anaesthesia).
      Recommendations for patient care facilities, patient care units and postoperative
      intensive care are summarized.

PMID- 17016322
TI  - Anaesthesia and medical disease.

PMID- 17016323
TI  - Perioperative considerations in the management of the patient taking herbal
      medicines.
AB  - The use of herbal products has recently increased dramatically in the United
      States. Patients are flocking to use these and many other complementary or
      alternative therapies. Perhaps disillusionment with managed care, loss of the
      traditional doctor-patient relationship, or simply increased access on store
      shelves, in the media, and on the Internet have all led to this increased use. As
      physicians, we are facing a paucity of information regarding the true dangers of
      these products, and there is virtually no information on how they may affect the
      perioperative milieu. The following review will discuss the limitations of Food
      and Drug Administration protection, and will review as well as provide an outline
      of the potential adverse reactions and side-effects that might affect anesthesia
      administration. To date, no double-blind, placebo-controlled studies have been
      carried out that specifically address herbal-anesthetic interactions or outcomes.

PMID- 17016324
TI  - Optimizing outcome in the very elderly surgical patient.
AB  - The number of very elderly patients undergoing surgery is expected to increase
      substantially in the first part of this century. This article reviews the recent
      findings on perioperative interventions that may improve the outcomes of this
      particularly challenging group of patients.

PMID- 17016325
TI  - Perioperative management of a common disorder: hereditary haemochromatosis.
AB  - Hereditary haemochromatosis is the commonest autosomal recessive disorder
      affecting Caucasian populations, and is readily diagnosed on the basis of
      elevated total body iron stores and genetic testing. Increased awareness of this
      disease in the community will hopefully prompt earlier testing and diagnosis.
      Treatment with regular phlebotomy is simple and effective and can prevent
      significant morbidity and mortality. Preoperative evaluation of patients with
      this disorder should consider the potential multisystem involvement in iron
      overload.

PMID- 17016326
TI  - Perioperative anesthetic management of the kidney-pancreas transplant recipient.
AB  - Patients undergoing simultaneous pancreas-kidney transplantation are at risk for
      a variety of serious perioperative complications. These are related to the
      chronic and acute problems associated with end-stage renal disease and insulin
      dependent diabetes mellitus and the prolonged, vascular and ductal surgery
      required to implant the two allografts. A number of strategies need to be
      integrated and diligently implemented to minimize the physiologic perturbations
      and complications related to the recipient's comorbid conditions and
      revascularization of the allografts. A major objective of the perioperative
      anesthetic management of simultaneous pancreas-kidney transplantation is to
      maximize cardiovascular performance in a way that provides optimum graft
      perfusion and recovery, while avoiding myocardial ischemia. Adherence to this
      objective, along with very effective immunosuppressants, surgical refinements,
      meticulous anesthetic preparation, extensive and frequent physiologic and
      metabolic monitoring, and quick response to abnormal findings has resulted in
      remarkably low recipient morbidity and mortality, and very high graft survival
      rates.

PMID- 17016327
TI  - Reperfusion injury in liver transplantation.
AB  - Reperfusion injury occurring in the transplanted liver is a complex lesion and
      has been the focus of considerable research over the past decade. This section
      will review recent major developments in understanding the mechanisms involved
      and their application to clinical transplantation.

PMID- 17016328
TI  - Transmission of viral disease in the operating room setting.
AB  - The transmission of viral disease in the operating room is an evolving problem.
      Advances in transfusion medicine have made blood supply safer than ever, whereas
      changes in transfusion practice have minimized the amount of blood transfused.
      The epidemiology of viral infection is changing in both the general population
      and among healthcare workers. Vaccination and prevention hold the key to future
      risk reduction for patients and providers.

PMID- 17016329
TI  - Minimizing intraoperative recall.
AB  - Intraoperative recall has plagued the administration of general anesthesia since
      the technique was first described, but the media's recent attention to the issue
      has heightened public awareness and brought it to the forefront of patient
      concerns. Now, more than ever, patients are asking about the possibility of
      'waking up during the operation'. The following review of the literature reveals
      potential strategies for reducing the risk and managing the sequelae of
      intraoperative recall.

PMID- 17016330
TI  - Blood conservation in patients undergoing non-cardiac surgery.
AB  - Concerns about the safety, inventory, and cost of allogeneic blood have led to a
      renewed interest in blood conservation. Autologous blood collection techniques,
      including preoperative autologous donation, acute normovolemic hemodilution, and
      perioperative blood recovery are routinely used as alternatives to allogeneic
      transfusion. In the future, these techniques may be combined with pharmacological
      strategies, such as presurgical erythropoietin therapy or red cell substitutes,
      to reduce further the need for allogeneic blood.

PMID- 17016332
TI  - Anaesthesia outside the operating room.

PMID- 17016331
TI  - Bibliography. Current world literature. Obstetric and gynaecological anaesthesia.

PMID- 17016333
TI  - Placement of aortic endoprostheses.
AB  - Endovascular stent-grafting has found its place in the elective treatment of 60%
      of abdominal or thoracic aortic lesions. The morbidity and mortality rates are
      clearly lower than those of classical repair but the results are suboptimal with
      9% residual endoleaks at 6 months. Anesthetic management with extensive
      monitoring even under local anesthesia remains mandatory and tends to reduce the
      postoperative care requirements. Future development will allow emergent
      endovascular treatment of ruptured aorta and further improvement will decrease
      the rate of late endoleaks.

PMID- 17016334
TI  - Sedation for endoscopy.
AB  - A review of the recent literature reveals an increasing published opinion in
      favour of unsedated endoscopy. However, recent studies show that the majority of
      US patients are unwilling or unable to tolerate this. In order for there to be a
      shift towards unsedated endoscopy, physicians will have to change patients'
      expectations. The indications for diagnostic and therapeutic endoscopic
      procedures continue to expand, involving increasingly complex techniques that
      require a high degree of patient cooperation. There is still a need to refine the
      sedative regimen for these cases.

PMID- 17016335
TI  - Anaesthesia for interventional neuroradiology.
AB  - Neuroradiologists have extended their treatment modalities in the field of
      vascular neurosurgery. The rapidly emerging and re-engineered neuroradiological
      techniques confront the anaesthetist with an increasing number of patients with
      severe neurological disease. More of these patients will need general anaesthesia
      in order to facilitate the endovascular procedure, including catheter placement,
      deposition of embolic material, and improved imaging. Anaesthetists are
      challenged by additional anaesthesiological aspects previously not encountered in
      neuroanaesthesia. A safe anaesthetic management is based on a broad understanding
      of pathophysiological and technical issues that arise with the endovascular
      treatment of cerebral vasculopathy.

PMID- 17016337
TI  - Mechanisms of anaesthesia: time to say farewell to the Meyer-Overton rule.

PMID- 17016336
TI  - Anaesthesia for magnetic resonance imaging/computed tomography.
AB  - The need for general anaesthesia for magnetic resonance imaging/computed
      tomography investigations can be reduced by the implementation of structured
      sedation programmes supervised by anaesthetists. Despite its side-effects,
      chloral hydrate is still the drug most widely used. Rectal thiopental or
      intravenous propofol are suggested anaesthetic agents for pre-school children and
      uncooperative or claustrophobic individuals. Spiral computed tomography scans and
      ultrafast magnetic resonance imaging shorten immobilization times further.
      However, functional magnetic resonance imaging and intervention techniques in
      neuroradiology depend on a motionless patient. A useful strategy for testing
      anaesthesia equipment has been outlined.

PMID- 17016338
TI  - Alpha2-adrenoceptor agonists in anaesthesia: a new paradigm.
AB  - Since the first report of alpha2-adrenoceptor agonists, the list of clinical
      indications for this class of drugs continues to expand. Alpha2-adrenoceptor
      agonists have several beneficial actions during the perioperative period. They
      exert a central sympatholytic action, thus improving haemodynamic stability in
      response to endotracheal intubation and surgical stress, reducing anaesthetic and
      opioid requirements, and causing sedation, anxiolysis and analgesia. Furthermore,
      alpha2-adrenoceptor agonists may offer benefits in the prophylaxis and treatment
      of perioperative myocardial ischaemia and their role in pain management and
      regional anaesthesia is increasing. The development of new, highly selective
      compounds which not only reduce anaesthetic requirements but induce anaesthesia
      by themselves may provide a new concept for the administration of anaesthesia.

PMID- 17016339
TI  - Xenon: a replacement for nitrous oxide.
AB  - Xenon is interesting despite its high cost because it is an almost ideal
      anaesthetic gas. This article describes developments in licensing issues,
      production and commercial delivery systems. Also, its effects on the
      cardiovascular, cerebral, respiratory, gastrointestinal and metabolic systems are
      discussed, along with analgesic sites of action and its effects at the cellular
      level.

PMID- 17016340
TI  - Pharmacokinetics and pharmacodynamics of remifentanil: an update in the year
      2000.
AB  - Remifentanil is still in its infancy in terms of postmarketing development. Its
      appropriate role in modern anesthesia care is still being defined and reports of
      novel clinical applications for remifentanil are frequently appearing in the
      anesthesia literature. This review will focus on selected advances in our
      understanding of remifentanil pharmacokinetics and pharmacodynamics and on newly
      proposed clinical applications for remifentanil.

PMID- 17016341
TI  - Tramadol today.
AB  - Tramadol is a unique analgesic offering moderate, dose-related pain relief
      through its action at multiple sites. In contrast to pure opioid agonists, it has
      a low risk of respiratory depression, tolerance and dependence. Troublesome side
      effects have been reported, but tramadol has been established as an adjunct to
      non-steroidal anti-inflammatory drugs in the treatment of moderate postoperative
      pain and to abolish shivering. It may have advantages in paediatric and day-case
      surgery and as an adjunct in local anaesthetic techniques. This review provides
      an evidence-based account of the role of tramadol in modern practice.

PMID- 17016342
TI  - Ketamine: a new look at an old drug.
AB  - Ketamine is a major drug for induction of patients with hypovolemia and for
      general anaesthesia under primitive conditions, but also has excellent properties
      for more generalized use in children, adults and other fragile patients.
      Potential beneficial effects on cardiac ischaemia and cerebral injury is
      presently explored, as well as the effects of ketamine as an potent analgesic
      drug. Combination with propofol or midazolam for sedation provides analgesia,
      sleep and spontaneous ventilation. The S-isomer of ketamine has a lower incidence
      of psychomimetic side effects in equianalgesic doses compared with the racemate
      or the R-isomer alone.

PMID- 17016343
TI  - Postoperative nausea and vomiting: prevention and therapy.
AB  - As we enter the new millennium, the armamentarium available to treat and prevent
      postoperative nausea and vomiting continues to expand. There remains a finite
      incidence of postoperative nausea and vomiting, particularly among high-risk
      populations. This review examines recent studies of drugs, both new and old, and
      their impact on postoperative nausea and vomiting prophylaxis and treatment.

PMID- 17016344
TI  - Rapacuronium.
AB  - Rapacuronium (Org 9487; ED90 = 1 mg x kg(-1)) is a new, low potency, short
      acting, non-depolarizing neuromuscular blocking agent. An intubating dose of
      1.5xED90 or 1.5 mg x kg(-1) of rapacuronium offers acceptable intubating
      conditions within 60-90 s in most patients. A complete block from this dose can
      be reversed immediately with satisfactory recovery in 12-16 min. Side-effects are
      dose-related and are mainly haemodynamic, i.e. an increase in heart rate and a
      decrease in blood pressure.

PMID- 17016345
TI  - Current world literature. Anaesthesia outside the operating room.

PMID- 17016346
TI  - Incremental science and the clinician.

PMID- 17016347
TI  - New developments in cerebrovascular surgery.
AB  - Major changes in the treatment of various cerebrovascular disorders have occurred
      with improvement and maturation of endovascular techniques. Embolization of
      intracranial aneurysms, angioplasty and stenting of extracranial and intracranial
      stenosis, as well as local intra-arterial delivery of thrombolytic agents in
      patients with acute stroke, are therapeutic modalities that are now widely
      available, with encouraging preliminary results. Pooling and analysis of the
      immense amount of data generated by the major carotid endarterectomy trials are
      defining particular subgroups of patients with carotid stenosis who are at higher
      risk of stroke who might particularly benefit from the operation. Unfortunately,
      no significant improvements have occurred in the treatment of some other
      conditions, such as parenchymal arteriovenous malformations and intracerebral
      hemorrhage.

PMID- 17016348
TI  - New developments in anaesthesia for neurological surgery.
AB  - The present review concentrates on the advances that have been made in three
      areas. First, the cerebrovascular effects of anaesthetic agents used for
      neurological surgery are considered. Second, recent data relating to the use of
      remifentanil are reviewed. Finally, two recent papers that have examined the
      place of anticoagulation in patients undergoing neurological surgery are
      evaluated.

PMID- 17016349
TI  - Process-based pharmacology in neuroanesthesia.
AB  - The present review focuses on the process by which selected pharmacologic agents
      can be employed in the management of specific problems that arise during surgical
      procedures, including tumor or trauma with elevated intracranial pressure,
      previously ruptured aneurysm, and procedures that may require some degree of
      controlled hypertension, such as carotid endarterectomy or temporary clipping. A
      balanced view between older established data, newer information, and long-term
      clinical practice in caring for such patients is presented. The emphasis is on
      intravenous rather than inhaled agents; issues that involve neuromuscular
      blockers are not addressed here.

PMID- 17016350
TI  - New developments in cerebral monitoring.
AB  - In past years, cerebral monitoring was mostly focused around global cerebral
      perfusion and metabolism monitoring, with the use of transcranial Doppler
      recordings, jugular bulb oximetry and near-infrared spectroscopy. Most of the
      recently introduced cerebral monitoring modalities, such as brain tissue partial
      oxygen tension monitoring and cerebral microdialysis, offer new opportunities by
      providing regional information on the specific brain area in which the probe is
      inserted. Ideally, these probes should be inserted in that area of the brain that
      is most vulnerable to ischaemia, but that may be salvageable with appropriate
      therapy. In this case, the combination of global and regional cerebral monitoring
      might offer the best information on which to base patient management. Also, the
      introduction of more clinically useful, functional neuroimaging techniques may be
      a valuable adjunct to future neurological critical care management.

PMID- 17016351
TI  - Neuroinflammation and infection.
AB  - Brain insults of various forms are always followed by a complex inflammatory
      reaction or cascade. This cascade has stimulated much research, and may be a
      target for future therapeutic interventions. During the cascade, both
      proinflammatory and anti-inflammatory processes are initiated, and tissue and
      neuronal repair mechanisms are also initiated. It is speculated that, because of
      the complex nature of the inflammatory reaction and its feedback loops, the
      future therapeutic manipulations in this area will be complex. Manipulation of
      inflammation may have beneficial effects in controlling the secondary
      inflammatory insult, but may be detrimental in blunting the anti-inflammatory and
      antioxidant responses to this inflammation, thus delaying initiation of tissue
      repair.

PMID- 17016352
TI  - Regional anesthesia.

PMID- 17016353
TI  - Combined regional and general anaesthesia.
AB  - Combining regional and general anaesthesia can have many advantages, particularly
      in patients undergoing major thoracic, abdominal or orthopaedic surgery. The use
      of regional anaesthetic techniques in anaesthetized children is an accepted
      standard of care, because needle and procedure phobias are very common and can
      result in severe anxiety, an inability to cooperate and sudden unpredictable
      movement. Epidural local anaesthetics have the potential of attenuating
      sympathetic hyperactivity, maintaining bowel peristalsis, sparing the use of
      opioids, and facilitating postoperative feeding and out-of-bed activity. Catheter
      techniques allow excellent and prolonged postoperative analgesia using epidural
      or peripheral nerve blocks. However, the superiority of regional techniques for
      hip fracture surgery and carotid endarterectomy has been disputed in several
      recent studies. As part of the combination technique, epidural block may in fact
      decrease blood flow in free flap surgery by a steal phenomenon, and increase
      intrapulmonary shunting during one-lung ventilation. The present review focuses
      on the use of a combination of regional and general anaesthesia for a variety of
      surgical procedures. It also compares the two anaesthetic techniques in elderly
      patients. The review is based on studies published during the past year.

PMID- 17016354
TI  - Regional versus general anesthesia.
AB  - The debate continues as to whether regional anesthesia is safer than general
      anesthesia. However, the choice of anesthetic technique is a complex decision.
      This review of the most recent publications compares the safety of regional
      anesthesia with that of general anesthesia.

PMID- 17016355
TI  - Regional anaesthesia and medical disease.
AB  - The present review addresses recent literature on advances in regional
      anaesthesia and medical diseases, and focuses on expert guidelines and decision
      making processes. Attention is also given to risk-benefit ratios in the
      management of patients with chronic illnesses, difficulties in treatment of the
      elderly, and associated morbidity and mortality.

PMID- 17016356
TI  - Specific nerve blocks: an update.
AB  - Recently there has been a considerable increase in interest in regional
      anesthesia and neural blockade. Many traditional nerve block techniques have been
      significantly modified to better fit the realm of both inpatient and outpatient
      surgery. The introduction of long acting local anesthetics with better safety
      profile as well as better equipment for continuous neuronal blockade has further
      increased the utility of peripheral nerve blocks. A significant effort has also
      been invested in studying and improving the safety of various techniques. These
      developments, coupled with an increased emphasis on teaching of regional blocks
      by organized anesthesia societies are likely to result in a wider use of these
      techniques in years to come.

PMID- 17016357
TI  - What is wrong with opioids in chronic pain?

PMID- 17016358
TI  - Phantom limb pain: cortical plasticity and novel therapeutic approaches.
AB  - Phantom limb pain is still a very frequent consequence of peripheral
      deafferentation or amputation of a limb. Recent findings from animal and
      neuroimaging studies suggest that phantom limb pain might be a central
      phenomenon, related to changes in the cortical, thalamic and spinal
      representation of the painful limb, and might be a type of somatosensory pain
      memory. Based on these assumptions, new treatment approaches focus on sensory
      discrimination training or motor cortex stimulation in an effort to influence
      cortical reorganization. Prevention of perpetuation of a somatosensory pain
      memory might also be possible through pharmacological agents such as N-methyl-D
      aspartate antagonists and gamma-aminobutyric acid agonists, substances that have
      been shown to influence and prevent cortical reorganization.

PMID- 17016359
TI  - Sodium channels and pain therapy.
AB  - Researchers have characterized changes in the nervous system that occur in
      response to tissue injury in order to identify possible targets for novel
      therapeutic interventions for the treatment of pain. That blockers of voltage
      gated sodium channels (VGSCs) are clinically effective for the treatment of pain
      associated with certain types of tissue injury suggests that these channels
      constitute such a target. Furthermore, there are changes in biophysical
      properties, expression, and/or distribution of VGSCs in subpopulations of primary
      afferent and central nervous system neurons in response to injury that are
      consistent with a role for VGSCs in the generation and maintenance of pain.
      Injury-induced changes in four unique VGSCs have been described. However, each of
      these channels appears to contribute to pain associated with different forms of
      injury in different ways.

PMID- 17016360
TI  - Neurotrophins, nociceptors and pain.
AB  - Nerve growth factor (NGF) is known to play a key role in the development of
      hyperalgesia after inflammatory injury. The increased levels of NGF that
      accompany injury lead to hyperalgesia via peripheral and central spinal
      mechanisms. New evidence reviewed here indicates that NGF can directly sensitize
      nociceptive neurones to noxious heat stimuli through rapid modulation of
      heat/vanilloid receptors or via de-novo increased expression of heat receptors.
      In addition, new data suggest that the central sensitization that can result from
      increased NGF may be mediated via central release of another neurotrophin, brain
      derived neurotrophic factor.

PMID- 17016361
TI  - Novel drugs for neuropathic pain.
AB  - Neuropathic pain is often inadequately controlled by conventional analgesics.
      Because the aetiology of neuropathic pain is only partially understood, specific
      treatment approaches have not been defined. A variety of pharmacological
      treatments have been proposed. However, for only a small minority of drugs used
      in neuropathic pain has the scientific evidence been evaluated in a satisfactory
      manner. The present review of the recent literature reveals the potential of
      certain novel drugs in treatment of neuropathic pain.

PMID- 17016363
TI  - Current world literature. Neuroanaesthesia.

PMID- 17016364
TI  - Ambulatory anaesthesia: cost reduction and patient safety presents a growing
      challenge.

PMID- 17016362
TI  - New insights into physiological and pathophysiological functions of cyclo
      oxygenase-2.
AB  - During the past few years specific inhibitors of the cyclo-oxygenase-2 enzyme
      have emerged as important pharmacological tools for treatment of patients with
      rheumatoid arthritis or osteoarthritis. In comparison to traditional nonsteroidal
      anti-inflammatory drugs, specific cyclo-oxygenase-2 inhibitors may provide equal
      efficacy in terms of antiinflammatory and analgesic action, with significantly
      fewer gastrointestinal side effects. Although cyclo-oxygenase-2 was once regarded
      as a source of pathological prostanoids, recent studies have indicated that this
      isoenzyme also fulfills a variety of physiological functions within the organism.
      The present review assesses recent advances in cyclo-oxygenase-2 research, with
      particular emphasis on new insights into the biology of this isoenzyme.

PMID- 17016365
TI  - Controversial issues in adult and paediatric ambulatory anaesthesia: is there a
      role for alpha-2 agonists in conscious sedation in adults and paediatric
      ambulatory surgical practice?
AB  - Ambulatory surgery has come to the fore in recent years, guided by the twin
      forces of healthcare economics and pharmacological innovations. In this review
      the authors will focus on alpha2-adrenergic agonists, a new class of
      sedative/analgesic agents and their possible application for conscious sedation
      in the ambulatory care setting. To put the alpha2-agonists into clinical context,
      we will discuss the currently available agents for general anaesthesia as well as
      for conscious sedation and their respective drawbacks. Thereafter we will compare
      and contrast the use of alpha2-agonists with clinically available agents, and
      speculate as to the direction this field is likely to take in the future.

PMID- 17016366
TI  - Do we need muscular blockers in ambulatory anaesthesia?
AB  - Since the introduction of the laryngeal mask airway, the majority of day case
      patients can safely be anaesthetized without the administration of muscle
      relaxants. If muscle relaxation is required, the modern non-depolarizing agents,
      vecuronium, rocuronium, atracurium, cisatracurium and mivacurium, provide an
      excellent choice. Succinylcholine should be regarded mainly as an option in the
      event of an emergency intubation, especially in paediatric patients.

PMID- 17016367
TI  - Total intravenous or balanced anaesthesia in ambulatory surgery?
AB  - General anaesthesia is still the most common anaesthetic technique in the
      ambulatory surgery setting. With the introduction of propofol, total intravenous
      anaesthesia gained widespread acceptance. Recently, the combination with
      remifentanil, an ultra-short acting opioid analgesic, allowed even more control
      over the duration of the anaesthetic. In comparison to propofol, however, the new
      inhalational anaesthetics desflurane and sevoflurane possess a pharmacokinetic
      profile that is preferable to that of propofol. Initial studies show that these
      pharmacokinetic advantages lead to a faster short-term recovery, although both
      substances have been associated with a higher incidence of postoperative nausea
      and vomiting. No differences have so far been demonstrated in respect to long
      term recovery, discharge from the post-anaesthesia care unit and discharge from
      the ambulatory care centre. Currently the anaesthesiologist has the possibility
      to choose his preferred anaesthetic technique based on individual patient needs,
      the surgery performed and the side-effects each technique may have. However, in
      contrast to the situation at the beginning of the 1990s total intravenous
      anaesthesia is not the technique that fits all needs but balanced anaesthesia
      presents an alternative.

PMID- 17016368
TI  - Anesthesia in ambulatory minimally invasive surgery.
AB  - The increasing popularity of minimally invasive surgery has grown concurrently
      with the demand for ambulatory surgery. Standard outpatient procedures such as
      tubal ligation are now being joined by ambulatory laparoscopic cholecystectomy.
      In order for ambulatory minimally invasive surgery to succeed, patient selection
      must be appropriate, careful attention paid to the physiologic changes of
      pneumoperitoneum, and pain and nausea treated pre-emptively.

PMID- 17016369
TI  - Fast-track regional anaesthesia.
AB  - Regional anaesthesia plays an important role in day case surgery because it
      combines reliable effects with low risk and the possibility of local
      postoperative analgesia without systemic side-effects. Fast-track regional
      anaesthesia allows short-term postoperative surveillance or even bypassing the
      post-anaesthesia care unit. Peripheral nerve blocks provide long-lasting pain
      relief, and can accelerate timely discharge if a persisting motor block is
      accepted. Multiple peripheral nerve stimulation and injection techniques may help
      to realize differential blockades with a pronounced analgesic rather than a motor
      blocking effect. Nerve blocks with local anaesthetics in combination with alpha2
      adrenoceptor agonists or non-steroidal anti-inflammatory drugs and short-acting
      parenteral opioids represent an effective multimodal concept for ambulatory
      surgery.

PMID- 17016370
TI  - Technology, education and training.

PMID- 17016371
TI  - Role of anaesthesiologists in undergraduate medical education.
AB  - Although anaesthesia and intensive care medicine are postgraduate subjects, few
      would deny the value of exposing medical undergraduates to clinical training in
      these areas. The present review addresses developments in medical undergraduate
      training curricula, and the specific benefits that can be provided for medical
      students, at all stages of training, by anaesthesiologists working in operating
      theatres, intensive care units and pain clinics.

PMID- 17016372
TI  - Simulation in anesthesia: the merits of large simulators versus small simulators.
AB  - Anesthesia simulation is generally perceived as involving large simulators that
      provide a limited number of operating room scenarios, especially crisis
      management. The scope of both anesthesia and flight simulation is much wider, and
      this review summarizes the range of the former. The areas where simulation has
      been used include training, education and science. The diversity of its uses may
      surprise the reader. The models that are used in simulations are important, and
      these are discussed in part of the discussion. As a result of the current
      imbalance in perception, I emphasize the merits of small simulators at the
      expense of large simulators.

PMID- 17016373
TI  - The role of transoesophageal echocardiography for anaesthetists.
AB  - Transoesophageal echocardiography has proved to be a valuable monitor of global
      and regional ventricular function in the perioperative period. In addition, it is
      increasingly used by anaesthetists as a diagnostic tool in patients with heart
      disease. During the past year, important steps towards quality assurance and the
      standardization of perioperative echocardiography were undertaken, and our
      understanding of the perioperative cardiovascular structure and function
      improved.

PMID- 17016374
TI  - The Objective Structured Clinical Exam - practical aspects.
AB  - Assessment of clinical skills in addition to factual knowledge has become part of
      the examination system in both undergraduate and postgraduate examinations. There
      is an increasing interest in the concept of competence and how it can be
      measured, particularly for the process of revalidation of practitioners. The
      Objective Structured Clinical Examination (OSCE) has been introduced for the
      assessment of clinical skills into postgraduate anaesthetic examinations in the
      United Kingdom. As with any examination, the issues regarding setting a standard
      are under continual review. The application of this exam format to the
      measurement of competency as well as skills has been the subject of scrutiny
      during the period reviewed. The literature suggests that competence is a much
      more complex construct than skill and that OSCE exams will be a contributory part
      but more work is required to establish assessment methods which will produce a
      global rating of competence. The role of the OSCE format in education as well as
      assessment has been examined and it is suggested that formative assessment can be
      made, and peer review learning brought about using an OSCE performed in teams.

PMID- 17016375
TI  - Current world literature. Ambulatory anaesthesia.

PMID- 17016376
TI  - Preoperative interventional cardiology in noncardiac surgery: benefit or risk?

PMID- 17016377
TI  - Cardiac arrhythmias: drugs and devices.
AB  - This review focuses on the important role played by the various types of remedial
      therapy in the prevention and treatment of perioperative cardiac arrhythmias. It
      discusses the new concepts of arrhythmogenesis and pro-arrhythmia; the long QT
      interval syndrome; newer, more selective class 3 antiarrhythmic drugs; cardiac
      rhythm management devices; drugs or devices used as prophylaxis for postoperative
      atrial arrhythmias; intravenous amiodarone for destabilizing ventricular
      arrhythmias; and preoperative potassium imbalance.

PMID- 17016378
TI  - Update on cardiopulmonary bypass.
AB  - Investigations into cardiopulmonary bypass continue to refine knowledge and
      clinical practice. Recent investigations have emphasized neurological
      complications, introducing the possibility of genetic predisposition as a risk
      factor. Appropriate flows, pressures, and hematocrit levels during
      cardiopulmonary bypass continue to create controversy. Whereas previous debate
      has centered around appropriate temperature management, recent discussions
      consider the possibility that mild hypothermia after cardiopulmonary bypass might
      be neuroprotective. Meta-analyses and prospective investigations continue to
      suggest the virtual equivalence of aprotinin and lysine analogues in reducing
      bleeding and transfusion after cardiopulmonary bypass. Several recent studies
      identified the mechanisms and severity of the inflammatory response to
      cardiopulmonary bypass, as well as possible techniques for attenuating
      inflammation.

PMID- 17016379
TI  - Regional anaesthesia in patients at coronary risk for noncardiac and cardiac
      surgery.
AB  - This review presents a brief overview about the role of regional anaesthesia in
      patients at risk for myocardial ischemia and/or infarction after cardiac and
      noncardiac surgical procedures. It includes pathophysiological insights in the
      problems of plaque rupture and the possible interactions by the use of regional
      anaesthesia. Special emphasis is put on the subject of thoracic epidural
      anaesthesia with newer studies showing improvement in relief of angina and
      improvement of global systolic and diastolic function in patients with coronary
      artery disease.

PMID- 17016380
TI  - Haemodynamic monitoring.
AB  - The monitoring of cardiovascular function is an indispensable element in
      anaesthesia. A thorough understanding of pathophysiology in various disease
      states allows optimal balancing of the invasiveness and completeness of
      haemodynamic monitoring. The prevention of both intraoperative and postoperative
      complications is therefore a primary goal.

PMID- 17016381
TI  - Interactions between cardiovascular treatments and anaesthesia.
AB  - Circulatory stability is one of the main objectives of the perioperative
      management of high-risk patients. Most of these patients are chronically treated
      with cardiovascular treatments, which interfere with the functioning of several
      physiological systems aimed at maintaining the circulatory status when the
      loading conditions of the heart deteriorate, or limit the compensatory mechanisms
      used when metabolic needs increase. Taking into account the pharmacology of these
      medications, their repercussions on perioperative haemodynamics and their
      potential beneficial effects on regional circulations, it has become possible to
      determine whether or not they must be given or withdrawn perioperatively.

PMID- 17016382
TI  - Postoperative intensive care in cardiac surgery.
AB  - Postoperative intensive care in cardiac surgery is a growing area, fuelled by the
      increase in the number of cardiac surgical procedures performed. An increase in
      the number of patients has resulted in increased resource utilization. Much of
      the recent research in this field is concerned with the early extubation of
      cardiac surgical patients, reducing the length of stay in the intensive care unit
      and predicting which patients will have delayed extubation and a prolonged length
      of stay. A number of recent studies have been published advocating 'off pump'
      cardiac surgery as a way of reducing the physiological insult of cardiopulmonary
      bypass and thereby improving the postoperative course. There is still
      insufficient evidence that this approach reduces morbidity and intensive care
      unit length of stay in multi-vessel off-pump coronary artery bypass surgery. The
      traditional design of post-cardiac surgical intensive care units and high
      dependency units has also recently been challenged. More flexible integrated
      units improve cost control and are more suited to modern cardiac surgery.

PMID- 17016384
TI  - Physiology of pulmonary perfusion: new concepts.
AB  - Regional pulmonary perfusion is spatially heterogeneous. The classic assumption
      has been that this is due to the influence of gravity. In the past decade, a new
      concept has emerged, stressing the fractal geometric properties of the pulmonary
      vascular tree. Studies that support the gravitational concept tend to have been
      elaborated using a lower resolution of measurement whereas experiments with high
      resolution measurements often yield results that contradict the gravitational
      hypothesis.

PMID- 17016385
TI  - Preoperative pulmonary evaluation: facts and myths.
AB  - This review summarizes recent reports on preoperative pulmonary evaluation
      focusing on the impact on outcome in thoracic and non-thoracic surgery. Data
      suggest that hitherto widely accepted pulmonary function tests do not predict
      perioperative complications. Therefore, they may not be considered alone to
      decide on the patient's operability. So-called prohibitive lung function
      parameters should no longer be used to deny a potentially curative lung
      resection. A more clinically oriented, interdisciplinary approach to severely
      compromised patients may be best suited to discuss and solve their problems.

PMID- 17016386
TI  - Optimizing preoperative lung function.
AB  - The exacerbation of chronic lung disease, bronchospasm, atelectasis, pneumonia,
      and respiratory failure with prolonged mechanical ventilation are considered to
      be clinically relevant postoperative pulmonary complications associated with
      increased morbidity and mortality. Careful history taking and a thorough physical
      examination are the most sensitive ways to identify patients at risk. Lung
      function tests serve as management tools for optimizing preoperative therapy and
      to assess postoperative lung function and individual risk in lung resection
      candidates. Additional cardiopulmonary exercise testing provides valuable
      information in borderline cases. The cessation of smoking, optimizing nutritional
      status and physiotherapy serve to prevent postoperative pulmonary complications.
      Moreover, medical therapy is recommended, especially for patients with
      obstructive airway diseases. In the absence of controlled clinical trials,
      medical therapy along the respective guidelines, with the primary goals of
      minimizing symptoms and improving lung function to the optimum seems to be a
      reasonable approach.

PMID- 17016387
TI  - Approaches to hypoxemia during single-lung ventilation.
AB  - Modern techniques to isolate the lungs, coupled with accurate continuous non
      invasive monitoring, have made single-lung ventilation safe and easy to perform.
      Most patients maintain an adequate arterial oxygen tension during single-lung
      ventilation. In order to maximize oxygenation, efforts are directed towards
      optimizing perfusion and ventilation to the ventilated lung or increasing the
      oxygen content of blood returning from the collapsed lung.

PMID- 17016388
TI  - Thoracic surgery in children.
AB  - Anesthesia for thoracic surgery in children covers a wide range of ages,
      associated disease processes, and surgical pathology. Therefore, the anesthetist
      must be prepared to deal with a diverse group of patients of all ages along the
      pediatric spectrum, combining knowledge regarding both pediatric and thoracic
      anesthesia. The following article reviews the anesthetic care of infants and
      children during thoracic surgery with emphasis on: (i) preoperative assessment;
      (ii) techniques for one-lung ventilation; (iii) anesthetic implications of
      specific procedures including laryngoscopy/bronchoscopy, thoracoscopic
      procedures, and open thoracotomy; and (iv) postoperative considerations including
      pain management.

PMID- 17016389
TI  - Perioperative pain management in patients undergoing thoracic surgery.
AB  - Adequate perioperative pain management has become an important part of thoracic
      anaesthesia. In the past few years, many trials have been performed to evaluate
      the efficacy of various analgesic regimens. This review summarizes the most
      frequently used analgesic techniques, with a particular emphasis on the results
      of studies and innovative ideas published between August 1999 and August 2000.

PMID- 17016391
TI  - Bad news about growth hormone treatment in the intensive care unit: need for some
      clarification.

PMID- 17016390
TI  - Current world literature.

PMID- 17016392
TI  - Feeding the intensive care patient.
AB  - The present review highlights recent findings (focusing on papers published
      between October 1999 and December 2000) in nutritional support of intensive care
      unit patients. During the past year, research focused on the use of enteral
      nutrition versus parenteral nutrition, and on the best composition of enteral
      nutrition and parenteral nutrition according to the clinical condition of the
      patient. With regard to enteral nutrition, the pH of nutritional support, the
      timing of administration and the technique of tube placement were debated.
      Immunomodulating agents and hormonal manipulations may improve outcomes of
      critically ill patients, but still warrant further research before they can be
      recommended for routine clinical use.

PMID- 17016393
TI  - What's new in the management of acute pancreatitis?
AB  - Acute severe pancreatitis remains a disease with multiple complications and high
      mortality rates. The body of knowledge about clinical pancreatitis is being
      subjected to rigorous evidence-based analysis, and relevant, practical guidelines
      have been issued. Great efforts are being made to identify and profile the
      mediators involved in the systemic hyperinflammatory response to acute pancreatic
      injury. Lexipafant, a platelet-activating factor antagonist that showed promising
      results in initial trials, failed to reduce the incidence of new organ failures
      or mortality in a large double-blind study. The search for an early and accurate
      prognostic marker for severity persists, with urinary trypsinogen activation
      peptide as a potentially suitable candidate. Patients with acute pancreatitis do
      not benefit from anti-secretory therapy with octreotide. Percutaneous,
      radiological, drainage techniques may eventually play an important role in the
      management of infected necrosis.

PMID- 17016394
TI  - Anticoagulation for continuous renal replacement therapy.
AB  - Anticoagulation during continuous renal replacement therapy should aim for an
      optimal filter performance allowing the delivery of an adequate dose of renal
      replacement therapy. On the other hand, the patient's safety should not be
      endangered. Although numerous options have been proposed, none of them appears to
      be ideal. Unfractionated heparin is still the most widely used anticoagulant.
      Reported experience with low-molecular-weight heparin is limited and does not
      confirm the anticipated increased safety. Regional citrate anticoagulation has
      been shown to reduce bleeding complications during continuous haemodialysis. A
      recent report demonstrates the feasibility and safety of citrate anticoagulation
      during continuous predilution haemofiltration. However, its use is labour
      intensive and the prevention of side-effects requires meticulous monitoring.
      Hirudin, a selective thrombin inhibitor, appears to be a suitable, although not
      completely safe, alternative in patients with heparin-induced thrombocytopenia.
      Continuous renal replacement therapy without anticoagulation may result in
      acceptable filter lives in patients with reduced coagulatory potential or an
      increased risk of bleeding. Although receiving little attention in the
      literature, the adequate selection of treatment characteristics may also
      contribute to an improved filter performance.

PMID- 17016395
TI  - What works in severe head injury?
AB  - Traumatic brain injury has an important socioeconomic impact in industrialized
      countries. However, well-conducted clinical trials are rare. Case-control studies
      have shown that prevention works. Pathophysiological understanding is becoming
      more complete as data on chemokines, local brain tissue oxygen tension and
      hypothermia accumulate. Multimodality monitoring will certainly assume greater
      importance in the future. Research with targeted therapeutic strategies indicates
      that secondary ischaemic insults can be prevented. Specific subgroups of patients
      with traumatic brain injury who will benefit from the use of hypothermia and
      barbiturates have been identified. Enteral feeding is the preferred nutritional
      strategy, and the follow-up period should be extended beyond the traditional 1
      year.

PMID- 17016396
TI  - Metabolic effects of vasoactive agents.
AB  - After adequate volume resuscitation, the mainstay of therapy in critically ill
      patients with shock is treatment with vasoactive substances to restore
      haemodynamics or to improve regional perfusion. These agents include adrenoceptor
      agonists with inotropic combined with either vasoconstricting or vasodilating
      effects, and predominantly vasodilating drugs such as prostacyclin and related
      compounds. However, vasoactive agents not only affect the cardiovascular system,
      but also have profound metabolic effects. The interdependence of vasoactive drugs
      with metabolism may be relevant regarding adequate oxygen and substrate delivery
      to cover actual organ needs. Therefore, the profiles of these metabolic effects
      have to be considered during their therapeutic administration.

PMID- 17016397
TI  - Mechanical ventilation in acute respiratory distress syndrome.
AB  - The acute respiratory distress syndrome occurs commonly in critical care. There
      is an increasing volume of clinical and experimental evidence that poor
      ventilatory technique that is injurious to the lungs can propagate the systemic
      inflammatory response and adversely affect mortality. Many ventilatory techniques
      have been hypothesized to 'protect' the lungs during mechanical ventilation,
      including tidal volume limitation, high positive end-expiratory pressure,
      pressure-controlled inverse ratio ventilation, and prone positioning.
      Experimental techniques include liquid ventilation, surfactant administration and
      extracorporeal gas exchange. Despite excellent rationale for their use, few
      techniques, apart from tidal volume limitation, have been shown to improve
      survival in randomized controlled trials.

PMID- 17016399
TI  - Basic and advanced life support, acute resuscitation, and cardiac resuscitation.
AB  - The global approach to resuscitation has changed dramatically in the past year.
      The groundwork for these changes began a decade ago with the development of the
      Utstein guidelines for uniform reporting of critical events. Consistency in data
      collection was necessary to enable evidence-based review and comparison of
      current practice. Resuscitation protocols have been significantly altered based
      upon these data. Basic life support (BLS) protocols have been simplified. Early
      access to electrical cardioversion is the key to survival. Mobilization of AED
      technology in the community is essential. Several issues were identified as
      crucial to future improvement of resuscitation statistics. Prevention strategies
      should be developed for high-risk patients. There is a need to identify cases in
      which resuscitation should not be started. Enhancement of educational methods to
      improve performance and retention of skills is key. Finally, the roadblocks for
      performance of ethical prospective research must be minimized.

PMID- 17016400
TI  - Trauma systems.
AB  - Trauma is one of the major causes of death and disability in modern society,
      particularly for the young. Organized trauma systems reduce mortality and
      morbidity from trauma. An effective trauma system addresses all aspects of trauma
      care, from prevention to rehabilitation. Well-developed trauma systems are
      currently available only to a minority of the world's population. Trauma systems
      in developed nations have much potential for improvement.

PMID- 17016401
TI  - Pre-hospital trauma care.
AB  - The chain of survival in outcome from major trauma is equally as important as its
      well established concept in survival from cardiac arrest. Preventive measures
      have been shown to be an effective means of reducing death from trauma, and the
      standard of pre-hospital care for those surviving the primary injury is improving
      in many trauma systems. The optimal pre-hospital interventions are still debated,
      but evidence suggests that patients with severe head injury in particular will
      benefit significantly from pre-hospital rapid-sequence intubation and field
      stabilization, whereas those with penetrating injury require rapid evacuation to
      hospital with minimal intervention. Pre-hospital asystole from trauma has a
      universally poor outcome. When delivering appropriate care, several helicopter
      based systems have shown improvements in outcome compared with ground-based
      systems. The International Liaison Committee on Resuscitation recently published
      guidelines on resuscitation, with particular relevance to pre-hospital trauma
      care. The importance of bystander cardiopulmonary resuscitation, oxygenation, and
      the avoidance of iatrogenic morbidity are stressed.

PMID- 17016402
TI  - New equipment and techniques for airway management in trauma.
AB  - A patent, unobstructed airway is fundamental in the care of the trauma patient,
      and is most often obtained by placing a cuffed tube in the trachea. The presence
      of shock, respiratory distress, a full stomach, maxillofacial trauma, neck
      hematoma, laryngeal disruption, cervical spine instability, and head injury all
      combine to increase tracheal intubation difficulty in the trauma patient.
      Complications resulting from intubation difficulties include brain injury,
      aspiration, trauma to the airway, and death. The use of devices such as the gum
      elastic bougie, McCoy laryngoscope, flexible and rigid fiberscopes, intubating
      laryngeal mask, light wand, and techniques such as rapid-sequence intubation,
      manual in-line axial stabilization, retrograde intubation, and cricothyroidotomy,
      enhance the ability to obtain a definitive airway safely. The management of the
      failed airway includes calling for assistance, optimal two-person bag-mask
      ventilation, and the use of the laryngeal mask airway, Combitube, or surgical
      airway. The simulation of airway management using realistic simulator tools (e.g.
      full-scale simulators, virtual reality airway simulators) is a promising modality
      for teaching physicians and advanced life support personnel emergency airway
      management skills.

PMID- 17016403
TI  - Acute trauma with multiple injuries.
AB  - Trauma with multiple injuries is a leading cause of death. It presents a
      diversity of challenges and requires many healthcare workers to care for its
      victims. Advances continue in the organization of pre-hospital care, the
      techniques of trauma surgery and critical care, and understanding the
      pathophysiology of traumatic injuries.

PMID- 17016404
TI  - Resuscitation from traumatic shock.
AB  - Shock is the body's response to decreased cellular perfusion. It can begin with
      hemorrhage, mechanical obstruction of the circulation, cardiac dysfunction,
      central nervous system injury, or sepsis. Once triggered, shock is perpetuated by
      the release of toxic compounds from ischemic cells. The treatment of shock
      consists of the removal or correction of the triggering pathology, followed by
      resuscitation back to the normal state. Clinical research in shock resuscitation
      in the past year has focused on recognizing the presence of shock in patients at
      risk, particularly those with normal vital signs but ongoing, occult
      hypoperfusion. In the laboratory, the emphasis has been on minimizing the initial
      hemorrhagic insult, minimizing the release of toxins from ischemic cells, and
      blocking the response to the toxins that are released.

PMID- 17016405
TI  - Fluid management of the trauma patient.
AB  - Hemodynamic instability in the trauma patient is most commonly secondary to blood
      loss and the accumulation of fluid in injured tissue. The etiologies of shock
      unrelated to hypovolemia must also be investigated. The treatment of hypovolemia
      in patients with non-cerebral trauma should begin with Ringer's lactate solution.
      Normal saline (0.9% sodium chloride) is appropriate for patients with head
      injury, alkalosis, or hyponatremia, but in large volumes may lead to metabolic
      acidosis. The role of colloids, hypertonic saline, and hemoglobin solutions in
      trauma resuscitation is unclear at the present time. Base deficit and lactate
      levels are useful as predictors of morbidity and mortality and can be used to
      guide resuscitation.

PMID- 17016406
TI  - The acute management of head injury.
AB  - The management of traumatic brain injury has undergone extensive revision as the
      results of large collaborative outcome studies have cast doubt on many
      traditional 'common sense' practices. The primary goal of identifying and
      treating intracranial hypertension has given way to a focus on secondary brain
      ischemia, in which cerebral perfusion pressure and oxygen delivery have gained
      new importance. With the exception of impending herniation, the routine use of
      hyperventilation and high-dose barbiturates is no longer recommended. Hypertonic
      saline, given as intermittent boluses, has joined mannitol as an effective means
      of reducing cerebral edema. Preliminary results from a large multi-center study
      have cast doubt on the benefit of the broad application of hypothermia in
      improving outcome in traumatic brain injury.

PMID- 17016407
TI  - Complications of pediatric trauma: effects on pediatric trauma anesthesia.
AB  - Pediatric trauma is a significant problem worldwide. The complications of
      pediatric trauma affect the emergency medical services provider, emergency
      physician, trauma surgeon, and anesthesiologist in different and challenging
      ways. Children have unique airway concerns, and require distinctive and safe
      approaches to protection of the airway. Moreover, the resuscitation of infants,
      children, and adolescents involved in trauma is complex and can be stressful for
      many caregivers. Therefore, the provision of anesthesia for acute pediatric
      trauma requires a synthesis of the usual issues of pediatric anesthesia with the
      overlying complications of trauma to effect an ideal anesthetic technique for
      each patient.

PMID- 17016408
TI  - Blunt thoraco-abdominal injury.
AB  - Recent advances in blunt thoraco-abdominal trauma management include improvements
      in imaging, particularly in trauma bay ultrasound. Indications for non-operative
      management have expanded for solid organ and aortic injury. The physiology of
      abdominal compartment syndrome continues to be defined, with resulting
      improvements in care.

PMID- 17016409
TI  - Pulmonary trauma.
AB  - Pulmonary trauma is common and devastating and is associated with significant
      morbidity and mortality. The present review highlights recent literature and case
      reports in this area. Topics of particular significance or interest include
      mechanisms of injury, potentially fatal intrathoracic vascular injuries,
      anesthetic management, fluid management (crystalloids as well as hemoglobin-based
      oxygen-carrying solutions), pain management of severe chest trauma, surgical
      management, and novel methods of diagnosis.

PMID- 17016410
TI  - Recent advances in burn care.
AB  - The patient with severe burn injuries offers significant challenges to the
      anesthesiologist. Inhalation injury continues to be the most significant
      contributor to morbidity and mortality despite recent advances in the techniques
      of mechanical ventilation and respiratory therapy. Operative procedures are
      complicated by the presence of severe pulmonary injury, massive blood loss,
      significant fluid shifts, and hypermetabolism, which alter the pharmacokinetics
      of many anesthetic agents. Recent advances in nutrition, respiratory support, the
      early excision of burns, and skin substitutes are improving survival from massive
      burns and decreasing the resultant disability.

PMID- 17016411
TI  - Current world literature.

PMID- 17016412
TI  - Accuracy of the blood pressure measurement.
AB  - Blood pressure measurement is the cornerstone for the diagnosis, the treatment
      and the research on arterial hypertension, and all of the decisions about one of
      these single aspects may be dramatically influenced by the accuracy of the
      measurement. Over the past 20 years or so, the accuracy of the conventional Riva
      Rocci/Korotkoff technique of blood pressure measurement has been questioned and
      efforts have been made to improve the technique with automated devices. In the
      same period, recognition of the phenomenon of white coat hypertension, whereby
      some individuals with an apparent increase in blood pressure have normal, or
      reduced, blood pressures when measurement is repeated away from the medical
      environment, has focused attention on methods of measurement that provide
      profiles of blood pressure behavior rather than relying on isolated measurements
      under circumstances that may in themselves influence the level of blood pressure
      recorded. These methodologies have included repeated measurements of blood
      pressure using the traditional technique, self-measurement of blood pressure in
      the home or work place, and ambulatory blood pressure measurement using
      innovative automated devices. The purpose of this review to serve as a source of
      practical information about the commonly used methods for blood pressure
      measurement: the traditional Riva-Rocci method and the automated methods.

PMID- 17016413
TI  - The pathophysiology of target organ damage in hypertension.
AB  - Hypertension is a common condition and a well-known risk factor for
      cardiovascular morbidity and mortality. Hypertension is also associated with
      damage or dysfunction with other organs in the body, causing strokes,
      proteinuria, renal failure and retinopathy. Damage/ dysfunction in these areas
      are commonly termed as hypertensive target organ damage (TOD). The development of
      TOD is a multifactorial process affecting various elements of vascular biology
      such as the renin-angiotensin-aldosterone system, prothrombotic states,
      inflammatory processes and endothelial function. These factors are inter-related
      in their contribution to the development of TOD. As hypertension is an important
      public health challenge worldwide a better understanding of the underlying
      pathophysiological processes leaving to its complications would be beneficial
      towards improving management strategies. The purpose of this review is to
      describe the various mechanisms involved in the pathogenesis of TOD and highlight
      recent advances in this field.

PMID- 17016414
TI  - Alpha-linolenic acid and cardiovascular diseases omega-3 fatty acids beyond
      eicosapentaenoic acid and docosahexaenoic acid.
AB  - Over the last decades, an increasing body of evidence has been accumulated on the
      beneficial effect of polyunsaturated fatty acids both in primary and secondary
      prevention of cardiovascular diseases. However, the vast majority of the studies
      has been performed on long-chain polyunsaturated fatty acids, such as
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and not on their
      biochemical precursor, alpha-linolenic acid (ALA). Actually, ALA has some other
      beneficial effects apart from the known antiarrhythmic effect. In fact, ALA has a
      strong inhibitory effect on omega-6 metabolic pathway. An adequate daily intake
      of ALA shifts metabolic pathway to EPA, so favoring the formation of products
      with a predominant antiaggregating and vasorelaxing action, with respect to
      eicosanoids with a predominant thrombotic effect. Some important evidences have
      been raised on the association between ALA and cardiovascular mortality. Indeed,
      dietary ALA has been associated with a lower rate of fatal and nonfatal coronary
      events. Hence, major scientific associations published nutritional guidelines
      including a specific recommendation for ALA.

PMID- 17016415
TI  - Diastolic failure in vascular surgery. A forgotten outcome predictor variable or
      not?
AB  - In vascular surgery, sometimes prediction of surgical outcome prior to surgery is
      next to impossible despite extensive history, requisite investigations and
      optimum perioperative management. It is well recognized that the leading cause of
      death in vascular surgery are cardiovascular events. Each surgeon remembers those
      patients sustaining morbidity and mortality despite the routine nature of surgery
      performed and the uncomplicated intraoperative course. In some patients the
      answer to the etiology regarding this observed poor outcome remains rhetorical
      and a mystery to be solved. Severity scores depend on the variables used, however
      if unknown recognized variables are not included, quality measurement of outcome
      in surgery becomes questionable. As surgeons become charged with evidence-based
      ideas, clinical observations will remain the child of updating both our own
      functional equations for outcome for ultimate improvement in patient care. Most
      patients with isolated diastolic dysfunction as the cause of their symptoms have
      hypertension or coronary artery disease or both (especially in the presence of
      renal dysfunction or diabetes mellitus) and can develop symptoms of heart failure
      in the absence of coronary obstructive picture. But could there be a way of
      approximating reality when predicting outcome?

PMID- 17016416
TI  - Strain rate imaging: data acquisition and postrocessing.
AB  - Several studies already demonstrated the clinical relevance of strain rate
      imaging. Unfortunately, so far only few echolaboratories are using this technique
      in their clinical practice. This is mainly due to the lack of information on how
      to perform a standard strain rate imaging study. Thus, the aim of the present
      review is to provide the bases and methodology to perform a correct strain rate
      study.

PMID- 17016417
TI  - Severe degenerative aortic stenosis: when a senile patient is a candidate for
      surgery.
AB  - Senile aortic stenosis is characterized by calcific degeneration of the valve
      that prevents the full opening of the cusps in systole. The disease may be silent
      for many years despite the presence of severe flow obstruction and generally is
      associated with aortic regurgitation and calcification of the coronary arteries.
      The continuous increase of the aged population with aortic stenosis entails
      difficult decisions in selecting the candidates for aortic valve replacement in
      order to optimize the timing for surgery. Although clinical examination is still
      fundamental for the diagnosis of the disease and the screening of the population,
      noninvasive assessment by Doppler echocardiography has transformed the management
      of these patients. The procedure allows better identification of patients who may
      benefit from valve replacement in particular in the setting of a ''low output/low
      gradient'' state and permits a follow-up of the progression of the disease in
      patients who are not yet candidates for surgery. It also allows a decrease in the
      utilization of invasive hemodynamics becoming a cost benefit tool for the health
      system. When performed properly, it is relatively time consuming, needs
      experience but offers major anatomic and hemodynamic data. Under these
      circumstances, cardiac catheterization is required only in cases when there is
      discordance between the clinical assessment and cardiac ultrasound evaluation. In
      this review we summarize the prevalence and significance of the disease in the
      elderly population and the use of all recent echocardiographic data that may help
      select the true candidates for surgery.

PMID- 17016418
TI  - Prognostic significance of atrial fibrillation in thrombolysed and non
      thrombolysed patients.
AB  - AIM: Atrial fibrillation (AF) is considered a frequent complication of acute
      myocardial infarction (AMI). The aim of this study was to examine the incidence
      and prognostic significance of AF complicating AMI. METHODS: A total of 848
      patients with AMI were examined evaluating: age, sex, coronary risk factors,
      incidence of AF, prior ischemic events, infarct location, electrocardiogram on
      admission, thrombolytic therapy, in-hospital complications and mortality.
      RESULTS: AF was recorded in 84 patients (9.9%). They were older (P<0.0001), less
      frequently smokers (P<0.007), had higher creatinekinase level (P<0.005) and more
      advanced heart failure (Killip class >or=2). AF was documented in non
      thrombolysed more than in thrombolysed patients (11.2% vs 7.5%). Overall
      mortality resulted significantly higher in patients with AF (P=0.001);
      nevertheless it did not result as independent predictor of mortality. Instead,
      independent predictors of mortality have been Killip class >or= II (P<0.0001),
      age (P<0.0001) and prior infarction (P<0.002 ). CONCLUSIONS: In our experience,
      AF cannot be considered an independent predictor of mortality. Contrary, advanced
      heart failure, either in thrombolysed or not-thrombolysed patients, is an
      independent predictor of AF and mortality. Nevertheless, AF represents an
      expression of advanced heart failure, that is worsened by the development of
      arrhythmia with severe consequences on prognosis.

PMID- 17016419
TI  - Is transcutaneous oxygen and carbon dioxide monitoring indispensable in short-
      and long-term therapeutic management of non-reconstructable lower critical limb
      ischemia?
AB  - AIM: The aim of this study was to evaluate the capacity of transcutaneous partial
      pressure of O(2) (TCpO(2)) and CO(2) (TCpCO(2)) to predict clinical response to
      pharmacological treatment in short- and long-term follow-up of unreconstructable
      critical limb ischemia (CLI) treated with prostanoids; to suggest a diagnostic
      and therapeutic algorithm able to define the possibility of prostanoid therapy in
      unreconstructable CLI at high risk of limb loss. METHODS: Twenty-six consecutive
      patients with CLI (21 with distal trophic lesions, 31 symptomatic limbs)
      considered unreconstructable after peripheral angiography and with a history of
      type 2 diabetes mellitus underwent daily parenteral Iloprost treatment for 2-3
      weeks. RESULTS: Transcutaneous gas-analytic monitoring (TGM) in non
      reconstructable CLI treated with Iloprost divided patients into 2 groups: early
      responders (ER) with increased TcpO(2) and normalization of TcpCO2, and non
      responders (NR) with unchanged TcpO(2) and TcpCO(2) parameters. In the NR who
      underwent a second cycle of Iloprost within a few months of the first, TGM
      further divided the patients into another subgroup of late responders (LR) with
      TcpO(2) and TcpCO(2) similar to the ER group and a subgroup of NR, who, after
      pharmacological treatment failure, should undergo eventual surgical re-timing
      and/or spinal cord stimulation in a final attempt to save the limb. CONCLUSIONS:
      In the short-term follow-up of CLI, a marked reduction in supine/dependent
      TcpO(2) and a marked increase in supine TcpCO(2) at the symptomatic forefoot
      proved to be significant predictors of major amputation risk. In the long-term
      follow-up period, TGM showed that, in ER and in LR, the favourable effect of
      pharmacological therapy observed in the first 6 months will disappear over the
      next 6 months, suggesting an algorithm of 2- to 3-week cycles of prostanoid
      therapy repeated every year. In NR treated with surgical and/or alternative
      therapies who did not undergo major amputations, prolonged instrumental TGM will
      provide a constant evaluation of metabolic parameters, thus providing the
      possibility to save the limb with additional pharmacological therapy.

PMID- 17016420
TI  - Unusual pacemaker implantation through a left sided superior vena cava via
      anonymous vein after heart transplantion.
AB  - We report the case of a 56-year-old male heart transplant recipient, who
      underwent postoperative pacemaker implantation through a left sided superior vena
      cava (LSVC) via anonymous vein. We describe our successful management of this
      case. We suggest that the specific anatomic conditions should be considered in
      all heart transplant recipients with LSVC if pacemaker implantation is necessary
      postoperatively.

PMID- 17016421
TI  - QT prolongation due to aortic aneurysm rupture and amiodarone in a patient with a
      H558R polymorphism in the cardiac sodium channel gene SCN5A.
AB  - The duration of the QT interval is influenced by many pathologic processes and
      drugs. We report a 74-year-old man who was admitted after syncope. His
      electrocardiogram (ECG) showed a QT interval of 0.44 s (QTc 0.53 s). After 10 h a
      ruptured abdominal aortic aneurysm was diagnosed and the patient underwent
      implantation of an aorto-bi-iliac Y-prosthesis. After surgery QT interval
      normalized. Under therapy with amiodarone, given because of atrial fibrillation,
      QT prolongation occurred again and disappeared after discontinuation of
      amiodarone. The postoperative course was complicated by critical illness
      polyneuropathy and plexopathy. Whereas amiodarone is a well recognized cause of
      QT prolongation, aortic aneurysm rupture has not been described previously.
      Vegetative mechanisms and sudden decrease of cardiac afterload due to the
      ruptured aneurysm may have altered myocardial repolarisation and thus prolonged
      QT interval duration. In conclusion in a patient with syncope and QT
      prolongation, extracardiac causes like rupture or an aortic aneurysm have to be
      included into the differential diagnosis.

PMID- 17016422
TI  - Abdominal aortic aneurysm associated with abdominal visceral diseases.
AB  - Abdominal aortic aneurysm (AAA) occurs in advanced age. As such, its frequency
      has increased with the general ageing of the population as has the possibility of
      finding AAA associated with abdominal visceral disease, especially neoplasms. A
      malignant mass is present in 4% of patients who undergo aortic reconstruction for
      AAA. Since surgical treatment for both is often potentially life-threatening, the
      surgeon is faced with a series of treatment decisions concerning foremost timing
      of the operation. The main worry is that simultaneous treatment carries a
      potential risk of infection of the vascular graft. On the other hand, a 2-phase
      procedure is also burdened by risks linked to a second anaesthesia and a second
      surgical operation carried out on scar or contaminated tissue and the worsening
      of one of the 2 potentially life-threatening illnesses. In this situation
      endovascular treatment of an AAA may represent an advantageous alternative
      therapeutic strategy.

PMID- 17016423
TI  - Drugs, their targets and the nature and number of drug targets.
AB  - What is a drug target? And how many such targets are there? Here, we consider the
      nature of drug targets, and by classifying known drug substances on the basis of
      the discussed principles we provide an estimation of the total number of current
      drug targets.

PMID- 17016424
TI  - Discovery and development of sorafenib: a multikinase inhibitor for treating
      cancer.
AB  - Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer
      has increased considerably, which has led to the discovery and development of
      targeted therapies tailored to inhibit cancer-specific pathways. The introduction
      and refinement of rapid, high-throughput screening technologies over the past
      decade has greatly facilitated this targeted discovery and development process.
      Here, we describe the discovery and continuing development of sorafenib
      (previously known as BAY 43-9006), the first oral multikinase inhibitor that
      targets Raf and affects tumour signalling and the tumour vasculature. The
      discovery cycle of sorafenib (Nexavar; Bayer Pharmaceuticals) - from initial
      screening for a lead compound to FDA approval for the treatment of advanced renal
      cell carcinoma in December 2005 - was completed in just 11 years, with approval
      being received approximately 5 years after the initiation of the first Phase I
      trial.

PMID- 17016426
TI  - Discovery and development of clofarabine: a nucleoside analogue for treating
      cancer.
AB  - The treatment of acute leukaemias, which are the most common paediatric cancers,
      has improved considerably in recent decades, with complete response rates
      approaching approximately 90% in some cases. However, there remains a major need
      for treatments for patients who do not achieve or maintain complete remission,
      for whom the prognosis is very poor. In this article, we describe the challenges
      involved in the discovery and development of clofarabine, a second-generation
      nucleoside analogue that received accelerated approval from the US FDA at the end
      of 2004 for the treatment of paediatric patients 1-21 years old with relapsed or
      refractory acute lymphoblastic leukaemia after at least two prior regimens. It is
      the first such drug to be approved for paediatric leukaemia in more than a
      decade, and the first to receive approval for paediatric use before adult use.

PMID- 17016425
TI  - Novel pharmacological targets for the treatment of Parkinson's disease.
AB  - Dopamine deficiency, caused by the degeneration of nigrostriatal dopaminergic
      neurons, is the cause of the major clinical motor symptoms of Parkinson's
      disease. These symptoms can be treated successfully with a range of drugs that
      include levodopa, inhibitors of the enzymatic breakdown of levodopa and dopamine
      agonists delivered by oral, subcutaneous, transcutaneous, intravenous or intra
      duodenal routes. However, Parkinson's disease involves degeneration of non
      dopaminergic neurons and the treatment of the resulting predominantly non-motor
      features remains a challenge. This review describes the important recent advances
      that underlie the development of novel dopaminergic and non-dopaminergic drugs
      for Parkinson's disease, and also for the motor complications that arise from the
      use of existing therapies.

PMID- 17016427
TI  - Signalling platforms that modulate the inflammatory response: new targets for
      drug development.
AB  - Therapeutically controlling inflammation is essential for the clinical management
      of many high-prevalence human diseases. Drugs that block the pro-inflammatory
      cytokines tumour-necrosis factor-alpha and interleukin-1 (IL-1) can improve
      outcomes for rheumatoid arthritis and other inflammatory diseases but many
      patients remain refractory to treatment. Here we explore the need for developing
      new types of anti-inflammatory drugs and the emergence of novel drug targets
      based on the clustering of IL-1 receptors into multi-protein aggregates
      associated with cell adhesions. Interference with receptor aggregation into multi
      protein complexes effectively abrogates IL-1 signalling. The exploration of the
      crucial molecules required for receptor clustering, and therefore signal
      transduction, offers new targets and scope for anti-inflammatory drug
      development.

PMID- 17016428
TI  - The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2
      driven mammary gland tumorigenesis.
AB  - There is increasing evidence for the role of wild-type p53 induced phosphatase 1
      (Wip1) phosphatase in the regulation of tumorigenesis. To evaluate Wip1 as a
      breast cancer oncogene, we generated a mouse strain with targeted expression of
      Wip1 to the breast epithelium. We found that these mice are prone to cancer when
      intercrossed with transgenics expressing the ErbB2 oncogene but not conditional
      knockouts for Brca2. This tumor-prone phenotype of Wip1 is fully eliminated
      through attenuation of proliferation by activating the MKK6/p38 mitogen-activated
      protein kinases (MAPK) cascade in mice bearing a constitutively active form of
      MKK6. We propose that Wip1 phosphatase operates within the MKK6/p38 MAPK
      signaling pathway to promote ErbB2-driven mammary gland tumorigenesis.

PMID- 17016429
TI  - Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in
      response to DNA damage.
AB  - We discovered a novel oncogene in a T-cell lymphoma cell line, multiple copies in
      T-cell lymphoma-1 (MCT-1), that has been shown to decrease cell-doubling time,
      shorten the duration of G(1) transit time and/or G(1)-S transition, and transform
      NIH3T3 fibroblasts. We subsequently demonstrated that there were significantly
      increased levels of MCT-1 protein in a subset of primary diffuse large B-cell
      lymphomas. Levels of MCT-1 protein were shown to be increased after exposure to
      DNA damaging agents. This increase did not require new protein synthesis,
      suggesting that post-translational mechanisms were involved. Phosphorylation is
      one potential mechanism by which the activity of molecules involved in cell
      cycle/survival is rapidly modulated. The RAS/mitogen-activated/extracellular
      regulated kinase (MEK)/extracellular signal-regulated kinases (ERK) pathway plays
      a prominent role in the regulation of cell growth and proliferation through
      phosphorylation-dependent regulation of several substrates. The MCT-1 protein is
      predicted to have numerous putative phosphorylation sites. Using a combination of
      genetic and pharmacological approaches, we established that phosphorylation of
      MCT-1 protein by p44/p42 mitogen-activated protein kinases is critical for
      stabilization of MCT-1 protein and for its ability to promote cell proliferation.
      Our data suggests that targeting the RAS/MEK/ERK signal transduction cascade may
      provide a potential therapeutic approach in lymphomas and related malignancies
      that exhibit high levels of MCT-1 protein.

PMID- 17016430
TI  - A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma.
AB  - Bcl-2 or Bcl-X(L) confers resistance to chemotherapy in multiple myeloma (MM).
      Here we characterized the effects of ABT-737, a potent small-molecule inhibitor
      of antiapoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w with markedly higher affinity
      than previously reported compounds, on human MM cells. ABT-737 induces apoptosis
      in MM cells, including those resistant to conventional therapy. Examination of
      purified patient MM cells demonstrated similar results, without significant
      toxicity against normal peripheral blood mononuclear cells and MM bone marrow
      stromal cells. Importantly, ABT-737 decreases the viability of bortezomib-,
      dexamethasone-(Dex) and thalidomide-refractory patient MM cells. Additionally,
      ABT-737 abrogates MM cell growth triggered by interleukin-6 or insulin-like
      growth factor-1. Mechanistic studies show that ABT-737-induced apoptosis is
      associated with activation of caspase-8, caspase-9 and caspase-3, followed by
      poly(ADP-ribose) polymerase cleavage. Combining ABT-737 with proteasome inhibitor
      bortezomib, melphalan or dexamethasone induces additive anti-MM activity. Taken
      together, our study provides the rationale for clinical protocols evaluating ABT
      737, alone and together with botezomib, mephalan or dexamethasone, to enhance MM
      cell killing, overcome drug resistance conferred by Bcl-2 and improve patient
      outcome in MM.

PMID- 17016431
TI  - p85 regulatory subunit of PI3K mediates cAMP-PKA and estrogens biological effects
      on growth and survival.
AB  - Cyclic adenosine 3'5' monophosphate (cAMP) and protein kinase A (PKA) cooperate
      with phosphatidylinositol 3' kinase (PI3K) signals in the control of growth and
      survival. To determine the molecular mechanism(s) involved, we identified and
      mutagenized a specific serine (residue 83) in p85alpha(PI3K), which is
      phosphorylated in vivo and in vitro by PKA. Expression of p85alpha(PI3K) mutants
      (alanine or aspartic substitutions) significantly altered the biological
      responses of the cells to cAMP. cAMP protection from anoikis was reduced in cells
      expressing the alanine version p85alpha(PI3K). These cells did not arrest in G1
      in the presence of cAMP, whereas cells expressing the aspartic mutant p85D
      accumulated in G1 even in the absence of cAMP. S phase was still efficiently
      inhibited by cAMP in cells expressing both mutants. The binding of PI3K to Ras
      p21 was greatly reduced in cells expressing p85A in the presence or absence of
      cAMP. Conversely, expression of the aspartic mutant stimulated robustly the
      binding of PI3K to p21 Ras in the presence of cAMP. Mutation in the Ser 83
      inhibited cAMP, but not PDGF stimulation of PI3K. Conversely, the p85D aspartic
      mutant amplified cAMP stimulation of PI3K activity. Phosphorylation of Ser 83 by
      cAMP-PKA in p85alpha(PI3K) was also necessary for estrogen signaling as
      expression of p85A or p85D mutants inhibited or amplified, respectively, the
      binding of estrogen receptor to p85alpha and AKT phosphorylation induced by
      estrogens. The data presented indicate that: (1) phosphorylation of Ser 83 in
      p85alpha(PI3K) is critical for cAMP-PKA induced G1 arrest and survival in mouse
      3T3 fibroblasts; (2) this site is necessary for amplification of estrogen signals
      by cAMP-PKA and related receptors. Finally, these data suggest a general
      mechanism of PI3K regulation by cAMP, operating in various cell types and under
      different conditions.

PMID- 17016432
TI  - Frizzled-7 dictates three-dimensional organization of colorectal cancer cell
      carcinoids.
AB  - Progression of colorectal cancer (CRC) involves spatial and temporal occurrences
      of epithelial-mesenchymal transition (EMT), whereby tumour cells acquire a more
      invasive and metastatic phenotype. Subsequently, the disseminated mesenchymal
      tumour cells must undergo a reverse transition (mesenchymal-epithelial
      transition, MET) at the site of metastases, as most metastases recapitulate the
      pathology of their corresponding primary tumours. Importantly, initiation of
      tumour growth at the secondary site is the rate-limiting step in metastasis.
      However, investigation of this dynamic reversible EMT and MET that underpins CRC
      morphogenesis has been hindered by a lack of suitable in vitro models. To this
      end, we have established a unique in vitro model of CRC morphogenesis, which we
      term LIM1863-Mph (morphogenetic). LIM1863-Mph cells spontaneously undergo cyclic
      transitions between two-dimensional monolayer (migratory, mesenchymal) and three
      dimensional sphere (carcinoid, epithelial) states. Using RNAi, we demonstrate
      that FZD7 is necessary for MET of the monolayer cells as loss of FZD7 results in
      the persistence of a mesenchymal state (increased SNAI2/decreased E-cadherin).
      Moreover, FZD7 is also required for migration of the LIM1863-Mph monolayer cells.
      During development, FZD7 orchestrates either migratory or epithelialization
      events depending on the context. Our findings strongly implicate similar
      functional diversity for FZD7 during CRC morphogenesis.

PMID- 17016433
TI  - Constitutive nitric oxide acting as a possible intercellular signaling molecule
      in the initiation of radiation-induced DNA double strand breaks in non-irradiated
      bystander cells.
AB  - The initiation and propagation of the early processes of bystander signaling
      induced by low-dose alpha-particle irradiation are very important for
      understanding the underlying mechanism of the bystander process. Our previous
      investigation showed that the medium collected from cell culture exposed to low
      dose alpha-particle rapidly induced phosphorylated form of H2AX protein foci
      formation among the non-irradiated medium receptor cells in a time-dependent
      manner. Using N(G)-methyl-L-arginine, 4-amino-5-methylamino-2',7'
      difluorofluorescein diacetate and N(omega)-nitro-L-arginine (L-NNA) treatment
      before exposure to 1 cGy alpha-particle, we showed in the present study that
      nitric oxide (NO(*)) produced in the irradiated cells was important and necessary
      for the DNA double strand break inducing activity (DIA) of conditioned medium and
      the generation of NO(*) in irradiated confluent AG1522 cells is in a time
      dependent manner and that almost all NO(*) was generated within 15 min post
      irradiation. Concurrently, the kinetics of NO(*) production in the medium of
      irradiated cells after irradiation was rapid and in a time-dependent manner as
      well, with a maximum yield observed at 10 min after irradiation with electron
      spin resonance analysis. Furthermore, our results that 7-Nitroindazole and L-NNA,
      but not aminoguanidine hemisulfate, treatment before exposure to 1 cGy alpha
      particle significantly decrease the DIA of the conditioned medium suggested that
      constitutive NO(*) from the irradiated cells possibly acted as an intercellular
      signaling molecule to initiate and activate the early process (<or=30 min) of
      bystander response after low-dose irradiation.

PMID- 17016434
TI  - The activation of TC10, a Rho small GTPase, contributes to v-Rel-mediated
      transformation.
AB  - v-Rel is the oncogenic member of the Rel/NF-kappaB family of transcription
      factors and transforms hematopoietic cells and fibroblasts. Differential display
      was employed to identify target genes that exhibit altered expression in v-Rel
      transformed cells. One of the cDNAs identified encodes the chicken ortholog of
      TC10, a member of the Rho small GTPase family. The expression of TC10 was
      increased in v-Rel-transformed chicken embryonic fibroblasts (CEFs) 3 to 6-fold
      relative to control cells at both the RNA and protein levels. An elevated level
      of active, GTP-bound TC10 was also detected in v-Rel-transformed cells relative
      to control cells. Expression of a dominant-negative TC10 mutant (TC10T32N)
      decreased the colony formation potential of v-Rel-transformed cells. Furthermore,
      overexpression of wild-type TC10 or a gain-of-function mutant (TC10Q76L) greatly
      enhanced the ability of v-Rel transformed CEFs to form colonies in soft agar. In
      addition to enhance the transformation potential of v-Rel, the overexpression of
      wild-type TC10 or the gain-of-function mutant alone enhanced the saturation
      density of CEFs and was sufficient for their anchorage-independent growth in
      vitro. These results indicate that elevated TC10 activity contributes to v-Rel
      mediated transformation of CEFs and demonstrate for the first time that a Rho
      factor alone is capable of inducing the in vitro transformation of primary cells.

PMID- 17016436
TI  - Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer.
AB  - The gene for E3 ubiquitin ligase WWP1 is located at 8q21, a region frequently
      amplified in human cancers, including prostate cancer. Recent studies have shown
      that WWP1 negatively regulates the TGFbeta tumor suppressor pathway by
      inactivating its molecular components, including Smad2, Smad4 and TbetaR1. These
      findings suggest an oncogenic role of WWP1 in carcinogenesis, but direct
      supporting evidence has been lacking. In this study, we examined WWP1 for gene
      dosage, mRNA expression, mutation and functions in a number of human prostate
      cancer samples. We found that the WWP1 gene had copy number gain in 15 of 34
      (44%) xenografts and cell lines from prostate cancer and 15 of 49 (31%) clinical
      prostate cancer samples. Consistently, WWP1 was overexpressed in 60% of
      xenografts and cell lines from prostate cancer. Mutation of WWP1 occurred
      infrequently in prostate cancer. Functionally, WWP1 overexpression promoted
      colony formation in the 22Rv1 prostate cancer cell line. In PC-3 prostate cancer
      cells, WWP1 knockdown significantly suppressed cell proliferation and enhanced
      TGFbeta-mediated growth inhibition. These findings suggest that WWP1 is an
      oncogene that undergoes genomic amplification at 8q21 in human prostate cancer,
      and WWP1 overexpression is a common mechanism involved in the inactivation of
      TGFbeta function in human cancer.

PMID- 17016435
TI  - Kruppel-like factor 4 exhibits antiapoptotic activity following gamma-radiation
      induced DNA damage.
AB  - In response to gamma-radiation-induced DNA damage, organisms either activate cell
      cycle checkpoint and repair machinery or undergo apoptosis to eliminate damaged
      cells. Although previous studies indicated that the tumor suppressor p53 is
      critically involved in mediating both responses, how a cell decides which pathway
      to take is not well established. The zinc-finger-containing transcription factor,
      Kruppel-like factor 4 (KLF4), is a crucial mediator for the checkpoint functions
      of p53 after gamma-irradiation and does so by inhibiting the transition from the
      G(1) to S and G(2) to M phases of the cell cycle. Here, we determined the role of
      KLF4 in modulating the apoptotic response following gamma-irradiation. In three
      independent cell systems including colorectal cancer cells and mouse embryo
      fibroblasts in which expression of KLF4 could be manipulated, we observed that
      gamma-irradiated cells underwent apoptosis if KLF4 was absent. In the presence of
      KLF4, the degree of apoptosis was significantly reduced and cells resorted to
      checkpoint arrest. The mechanism by which KLF4 accomplished this antiapoptotic
      effect is by activating expression of the cell cycle arrest gene, p21(WAF1/CIP1),
      and by inhibiting the ability of p53 to transactivate expression of the
      proapoptotic gene, BAX. Results of our study illustrate an unexpected
      antiapoptotic function of KLF4, heretofore considered a tumor suppressor in
      colorectal cancer, and suggest that KLF4 may be an important determinant of cell
      fate following gamma-radiation-induced DNA damage.

PMID- 17016437
TI  - AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and
      VEGF expression in multiple myeloma cells.
AB  - We recently demonstrated that the mammalian target of rapamycin (mTOR) inhibitor,
      CCI-779, curtailed the growth of a subcutaneous challenge of multiple myeloma
      (MM) cells in immunodeficient mice. This antitumor effect was associated with
      prevention of cell proliferation, induction of apoptosis and inhibition of
      angiogenesis. Interestingly, myeloma tumors with heightened AKT activation were
      particularly sensitive to a CCI-779-induced antitumor response. To investigate
      whether part of the differential sensitivity was due to an AKT-regulated effect
      on angiogenesis, we compared the effects of mTOR inhibitors against isogenic MM
      cell lines that only differ by their degree of AKT activity. In this model,
      heightened AKT activity significantly sensitized MM cells to the following
      inhibitory effects of mTOR inhibition: angiogenesis in vivo, vascular endothelial
      growth factor (VEGF) expression in vitro and in vivo and VEGF translation (but
      not transcription). Assessment of p70S6 kinase activity indicated that rapamycin
      induced comparable mTOR inhibition in both cell lines suggesting that an adverse
      effect on VEGF cap-dependent translation would be comparable. Internal ribosome
      entry site (IRES)-mediated cap-independent translation is a salvage pathway for
      protein expression when mTOR is inhibited, so we analyzed a possible regulatory
      role of AKT on VEGF IRES activity. We found that elevated AKT activity inhibited
      VEGF IRES function. These results support a mechanism whereby AKT prevents VEGF
      IRES activity in myeloma cells during mTOR inhibition resulting in a more
      complete abrogation of VEGF translation, and ultimately, angiogenesis.

PMID- 17016438
TI  - Inhibition of IGF-I receptor in anchorage-independence attenuates GSK-3beta
      constitutive phosphorylation and compromises growth and survival of
      medulloblastoma cell lines.
AB  - We have previously reported that insulin-like growth factor-I (IGF-I) supports
      growth and survival of mouse and human medulloblastoma cell lines, and that IGF-I
      receptor (IGF-IR) is constitutively phosphorylated in human medulloblastoma
      clinical samples. Here, we demonstrate that a specific inhibitor of insulin-like
      growth factor-I receptor (IGF-IR), NVP-AEW541, attenuated growth and survival of
      mouse (BsB8) and human (D384, Daoy) medulloblastoma cell lines. Cell cycle
      analysis demonstrated that G1 arrest and apoptosis contributed to the action of
      NVP-AEW54. Interestingly, very aggressive BsB8 cells, which derive from
      cerebellar tumors of transgenic mice expressing viral oncoprotein (large T
      antigen from human polyomavirus JC) became much more sensitive to NVP-AEW541 when
      exposed to anchorage-independent culture conditions. This high sensitivity to NVP
      AEW54 in suspension was accompanied by the loss of GSK-3beta constitutive
      phosphorylation and was independent from T-antigen-mediated cellular events
      (Supplementary Materials). BsB8 cells were partially rescued from NVP-AEW541 by
      GSK3beta inhibitor, lithium chloride and were sensitized by GSK3beta activator,
      sodium nitroprusside (SNP). Importantly, human medulloblastoma cells, D384, which
      demonstrated partial resistance to NVP-AEW541 in suspension cultures, become much
      more sensitive following SNP-mediated GSK3beta dephosphorylation (activation).
      Our results indicate that hypersensitivity of medulloblastoma cells in anchorage
      independence is linked to GSK-3beta activity and suggest that pharmacological
      intervention against IGF-IR with simultaneous activation of GSK3beta could be
      highly effective against medulloblastomas, which have intrinsic ability of
      disseminating the CNS via cerebrospinal fluid.

PMID- 17016439
TI  - RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary
      kidney cancer gene.
AB  - TRC8/RNF139 and von Hippel-Lindau (VHL) both encode E3 ubiquitin (Ub) ligases
      mutated in clear-cell renal carcinomas (ccRCC). VHL, inactivated in nearly 70% of
      ccRCCs, is a tumor suppressor encoding the targeting subunit for a Ub ligase
      complex that downregulates hypoxia-inducible factor-alpha. TRC8/RNF139 is a
      putative tumor suppressor containing a sterol-sensing domain and a RING-H2 motif
      essential for Ub ligase activity. Here we report that human kidney cells are
      growth inhibited by TRC8. Inhibition is manifested by G2/M arrest, decreased DNA
      synthesis and increased apoptosis and is dependent upon the Ub ligase activity of
      the RING domain. Tumor formation in a nude mouse model is inhibited by TRC8 in a
      RING-dependent manner. Expression of TRC8 represses genes involved in cholesterol
      and fatty acid biosynthesis that are transcriptionally regulated by the sterol
      response element binding proteins (SREBPs). Expression of activated SREBP-1a
      partially restores the growth of TRC8-inhibited cells. These data suggest that
      TRC8 modulation of SREBP activity comprises a novel regulatory link between
      growth control and the cholesterol/lipid homeostasis pathway.

PMID- 17016440
TI  - STAT1-independent inhibition of cyclooxygenase-2 expression by IFNgamma; a common
      pathway of IFNgamma-mediated gene repression but not gene activation.
AB  - Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of
      prostaglandins, promotes the development of colorectal cancer, and is a key
      molecular target of non-steroidal anti-inflammatory drugs, compounds that reduce
      the relative risk of developing colon cancer. In this study, we showed that
      interferon gamma (IFNgamma) inhibits the expression of COX-2 protein in
      intestinal epithelial cells (IECs) through a pathway that requires Janus
      activated kinase (JAK) activity. In contrast, we demonstrated that
      transcriptional inhibition of COX-2 by IFNbeta or IFNgamma occurs in cells with
      silenced signal transducer and activator of transcription 1 (STAT1) expression
      and that IFNs retained the ability to inhibit COX-2 transcription in cells with
      activated RasV12, in which IFNgamma failed to induce STAT1. Thus, unlike the
      activity of JAK, STAT1 is not required for the inhibition of COX-2 expression by
      IFNgamma. In contrast to COX-2, the activation of genes in response to IFNgamma,
      such as interferon regulatory factor-1, was severely impaired by both STAT1
      silencing and by constitutive Ras signaling. To determine whether there is a
      general differential requirement for STAT1 in gene activation and gene repression
      in response to IFNgamma in intestinal cells, we performed genome-wide analysis of
      IFNgamma target genes in an IEC line in which STAT1 expression was silenced by
      small interfering RNA. The results confirmed that the activation of the majority
      of genes by IFNgamma required STAT1. In contrast, the repression of several
      genes, as we showed for COX-2 specifically, was largely unaffected in cells with
      silenced STAT1. Our results therefore demonstrate that in general gene activation
      by IFNgamma is more sensitive to STAT1 deficiency than gene repression, and
      suggest that IFNgamma activates and represses gene expression via distinct
      pathways that can be distinguished, at least in part, by their requirement for
      STAT1.

PMID- 17016441
TI  - BRCA1 dysfunction in sporadic basal-like breast cancer.
AB  - Basal-like breast cancers form a distinct subtype of breast cancer characterized
      by the expression of markers expressed in normal basal/myoepithelial cells.
      Breast cancers arising in carriers of germline BRCA1 mutations are predominately
      of basal-like type, suggesting that BRCA1 dysfunction may play a role in the
      pathogenesis of sporadic basal-like cancers. We analysed 37 sporadic breast
      cancers expressing the basal marker cytokeratin 5/6, and age- and grade-matched
      controls, for downregulation of BRCA1. Although BRCA1 promoter methylation was no
      more common in basal-like cancers (basal 14% vs controls 11%, P=0.72), BRCA1
      messenger RNA expression was twofold lower in basal-like breast cancers compared
      to matched controls (P=0.008). ID4, a negative regulator of BRCA1, was expressed
      at 9.1-fold higher levels in basal-like breast cancer (P<0.0001), suggesting a
      potential mechanism of BRCA1 downregulation. BRCA1 downregulation correlated with
      the presence of multiple basal markers, revealing heterogeneity in the basal-like
      phenotype. Finally, we found that 63% of metaplastic breast cancers, a rare type
      of basal-like cancers, had BRCA1 methylation, in comparison to 12% of controls
      (P<0.0001). The high prevalence of BRCA1 dysfunction identified in this study
      could be exploited in the development of novel approaches to targeted treatment
      of basal-like breast cancer.

PMID- 17016443
TI  - UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas.
AB  - The UbcH10 gene codes for a protein that belongs to the ubiquitin-conjugating
      enzyme family. Previous studies of our group suggest UbcH10 expression as a valid
      indicator of the proliferative and aggressive status of thyroid carcinomas.
      Therefore, to better understand the process of ovarian carcinogenesis, and to
      look for possible tools to be used as prognostic markers in these neoplasias, we
      decided to extend the analysis of the UbcH10 expression to the ovarian neoplastic
      disease. We found that the UbcH10 gene was upregulated in some ovarian carcinoma
      cell lines analysed. Then, immunohistochemical studies demonstrate that UbcH10
      expression significantly correlates with the tumor grade and the undifferentiated
      histotype of the ovarian carcinomas. Furthermore, a significant relationship
      between UbcH10 expression and overall survival was observed. Finally, the block
      of UbcH10 protein synthesis by RNA interference inhibited the growth of ovarian
      carcinoma cell lines, suggesting a role of UbcH10 overexpression in ovarian
      carcinogenesis. Therefore, all these data taken together suggest the possibility
      to use UbcH10 detection as a marker for the diagnosis and prognosis of these
      neoplastic diseases and open the perspective of a therapy of some ovarian
      carcinomas based on the suppression of the UbcH10 synthesis and/or function.

PMID- 17016442
TI  - Interferon regulatory factor-1 regulates reconstituted extracellular matrix
      (rECM)-mediated apoptosis in human mammary epithelial cells.
AB  - Interactions between extracellular matrix (ECM) and mammary epithelial cells are
      critical for mammary gland homeostasis and apoptotic signaling. Interferon
      regulatory factor-1 (IRF-1) is a transcriptional regulator that promotes
      apoptosis during mammary gland involution and p53-independent apoptosis. We have
      recently shown that rapid cell surface tamoxifen (Tam) signaling promotes
      apoptosis in normal human mammary epithelial cells that were acutely damaged by
      expression of human papillomavirus type-16 E6 protein (*HMEC-E6). Apoptosis was
      mediated by recruitment of CREB-binding protein (CBP) to the gamma-activating
      sequence (GAS) element of the IRF-1 promoter, induction of IRF-1 and caspase-1/-3
      activation. Here, we show that growth factor-depleted, reconstituted ECM (rECM),
      similar to Tam, promotes apoptosis in *HMEC-E6 cells through induction of IRF-1.
      Apoptosis was temporally associated with recruitment of CBP to the GAS element of
      the IRF-1 promoter, induction of IRF-1 expression and caspase-1/-3 activation.
      Small interfering RNA-mediated suppression of IRF-1 protein expression in *HMEC
      E6 cells blocked (1) induction of IRF-1, (2) caspase-1/-3 activation and (3)
      apoptosis. These observations demonstrate that IRF-1 promotes rECM-mediated
      apoptosis and provide evidence that both rECM and rapid Tam signaling
      transcriptionally activate IRF-1 through recruitment of CBP to the IRF-1 GAS
      promoter complex.

PMID- 17016444
TI  - Absence of tyrosine kinase mutations in Japanese colorectal cancer patients.
AB  - Tyrosine kinases, which are important regulators of intracellular signal
      transduction pathways, have mutated forms that are often associated with
      oncogenesis and are attractive targets for therapeutic intervention. Recently,
      systematic mutational analyses of tyrosine kinases revealed that a minimum of 30%
      of colorectal cancer contain at least one mutation in the tyrosine kinases. To
      further explore these mutations, we examined all reported mutations of NTRK3,
      FES, KDR, EPHA3, NTRK2, JAK1, PDGFRA, EPHA7, EPHA8, ERBB4, FGFR1, MLK4 and GUCY2F
      genes in the 24 colorectal cancer cell lines. Unexpectedly, among 24 colorectal
      cancer cell lines, only two cell lines (LoVo and CaR1) harbored mutation C1408T
      (R470C) in MLK4 gene. The mutation rate was extremely low compared to that
      previously reported. Therefore, we analyzed mutations in 46 colorectal cancer
      samples resected from the same number of Japanese patients. Surprisingly, none of
      the 46 samples contained any of the mutations reported. Based on our study, we
      advise that a more comprehensive tyrosine kinase gene mutation assay is necessary
      in the future.

PMID- 17016445
TI  - Chaperoning of estrogen receptor and induction of mammary gland proliferation by
      neuronal protein synuclein gamma.
AB  - Synucleins are emerging as central players in the formation of pathologically
      insoluble deposits characteristic of neurodegenerative diseases. However,
      synuclein gamma (SNCG), previously identified as a breast cancer specific gene
      (BCSG1), is also highly associated with breast cancer progression. Using
      transgenic mouse model, we demonstrated a role of SNCG in induction of highly
      proliferative pregnancy-like phenotype of mammary epithelial cells and branching
      morphology. SNCG participated in the heat shock protein-based multiprotein
      chaperone complex for steroid receptor signaling. Expression of SNCG in mammary
      epithelium resulted in a significant stimulation of ERalpha transcriptional
      activity. SNCG-induced mammary gland proliferation can be effectively blocked by
      antiestrogen and ovariectomy, indicating that the induced proliferation is
      mediated by ERalpha signaling and requires estrogen stimulation. These data
      indicate the chaperone activity of SNCG on stimulation of steroid receptor
      signaling in mammary gland and, thus induces extensive mammary gland
      proliferation and contributes to the hormonal impact on mammary tumorigenesis.

PMID- 17016446
TI  - Tumor suppressor activity of glucocorticoid receptor in the prostate.
AB  - Glucocorticoids are extensively used in combination chemotherapy of advanced
      prostate cancer (PC). Little is known, however, about the status of the
      glucocorticoid receptor (GR) in PC. We evaluated over 200 prostate samples and
      determined that GR expression was strongly decreased or absent in 70-85% of PC.
      Similar to PC tumors, some PC cell lines, including LNCaP, also lack GR. To
      understand the role of GR, we reconstituted its expression in LNCaP cells using
      lentiviral approach. Treatment of LNCaP-GR cells with the glucocorticoids
      strongly inhibited proliferation in the monolayer cultures and blocked anchorage
      independent growth. This was accompanied by upregulation of p21 and p27, down
      regulation of cyclin D1 expression and c-Myc phosphorylation. Importantly, the
      activation of GR resulted in normalized expression of PC markers hepsin, AMACR,
      and maspin. On the signaling level, GR decreased expression and inhibited
      activity of the MAP-kinases (MAPKs) including p38, JNK/SAPK, Mek1/2 and Erk1/2.
      We also found that activation of GR inhibited activity of numerous transcription
      factors (TF) including AP-1, SRF, NF-kappaB, p53, ATF-2, CEBPalpha, Ets-1, Elk-1,
      STAT1 and others, many of which are regulated via MAPK cascade. The structural
      analysis of hepsin and AMACR promoters provided the mechanistic rationale for PC
      marker downregulation by glucocorticoids via inhibition of specific TFs. Our data
      suggest that GR functions as a tumor suppressor in prostate, and inhibits
      multiple signaling pathways and transcriptional factors involved in proliferation
      and transformation.

PMID- 17016447
TI  - Decisions, decisions.

PMID- 17016448
TI  - Comparing genomes and languages using current knowledge.

PMID- 17016450
TI  - Are you experienced? Junior scientists should make the most of opportunities to
      develop skills outside the laboratory.

PMID- 17016449
TI  - Who are we? Indigenous microbes and the ecology of human diseases.

PMID- 17016451
TI  - Tagging products and people. Despite much controversy, radiofrequency
      identification chips have great potential in healthcare.

PMID- 17016452
TI  - The costs of REACH. REACH is largely welcomed, but the requirement to test
      existing chemicals for adverse effects is not good news for all.

PMID- 17016453
TI  - A quantum leap in biology. One inscrutable field helps another, as quantum
      physics unravels consciousness.

PMID- 17016455
TI  - Hitching a ride.

PMID- 17016456
TI  - Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family.
AB  - Several of the inhibitor of apoptosis protein (IAP) family members regulate
      apoptosis in response to various cellular assaults. Some members are also
      involved in cell signalling, mitosis and targeting proteins to the ubiquitin
      proteasome degradation machinery. The most intensively studied family member, X
      linked IAP (XIAP), is a potent inhibitor of caspase activity; hence, it is
      generally assumed that direct caspase inhibition is an important conserved
      function of most members of the family. Biochemical and structural studies have
      precisely mapped the elements of XIAP required for caspase inhibition.
      Intriguingly, these elements are not conserved among IAPs. Here, we review
      current knowledge of the caspase-inhibitory potential of the human IAPs and show
      that XIAP is probably the only bona fide caspase inhibitor, suggesting that the
      other family members never gained the ability to directly inhibit caspase
      activity.

PMID- 17016457
TI  - Entering neurons: botulinum toxins and synaptic vesicle recycling.
AB  - Botulinum toxins are metalloproteases that act inside nerve terminals and block
      neurotransmitter release through their cleavage of components of the exocytosis
      machinery. These toxins are used to treat human diseases that are characterized
      by hyperfunction of cholinergic terminals. Recently, evidence has accumulated
      that gangliosides and synaptic vesicle proteins cooperate to mediate toxin
      binding to the presynaptic terminal. The differential distribution of synaptic
      vesicle protein receptors, gangliosides and toxin substrates in distinct neuronal
      populations opens up the possibility of using different serotypes of botulinum
      toxins for the treatment of central nervous system diseases caused by altered
      activity of selected neuronal populations.

PMID- 17016458
TI  - Molecular gymnastics at the herpesvirus surface.
AB  - This review analyses recent structural results that provide clues about a
      possible molecular mechanism for the transmission of a fusogenic signal among the
      envelope glycoproteins of the herpes simplex virus on receptor binding by
      glycoprotein gD. This signal triggers the membrane-fusion machinery of the virus-
      contained in glycoproteins gB, gH and gL--to induce the merging of viral and
      cellular membranes, and to allow virus entry into target cells. This activating
      process parallels that of gamma-retroviruses, in which receptor binding by the
      amino-terminal domain of the envelope protein activates the fusogenic potential
      of the virion in a similar way, despite the different organization of the
      envelope complexes of these two types of viruses. Therefore, the new structural
      results on the interaction of gD with its receptors might also provide insights
      into the mechanism of fusogenic signal transmission in gamma-retroviruses.
      Furthermore, the fusion activation parallels with retroviruses, together with the
      recently reported structural homology of gB with the rhabdovirus envelope
      glycoprotein indicate that the complex entry apparatus of herpesviruses appears
      to be functionally related to that of simpler enveloped viruses.

PMID- 17016460
TI  - Alcohol debridement for recurrent corneal erosions.

PMID- 17016461
TI  - Attitudes and behaviour of ophthalmologists to smoking cessation.
AB  - AIMS: Growing evidence suggests a causal association between smoking and eye
      disease. This study explores the current beliefs and practice among UK consultant
      ophthalmologists towards delivering smoking cessation advice to eye clinic
      attenders. METHODS: A cross-sectional survey using a postal questionnaire of all
      UK NHS hospital based consultant ophthalmologists was conducted. The
      questionnaire explored whether: ophthalmologists identify the smoking status of
      their patients, advise about the increased risk of eye diseases among smokers,
      and deliver smoking cessation advice. The availability of departmental smoking
      cessation resources was also ascertained. RESULTS: The response rate was 55%
      (485/886). Of the responders 79% were males. Only 35% of responders asked about
      smoking status every time or most times for new patients and 5% for follow-up
      patients. In all, 40% claimed to always or usually advise patients to quit
      smoking and 61% claimed to always or usually mention eye disease as a reason to
      quit. Only 14% assessed motivation to quit and 22% provided advice and assistance
      about how to stop smoking to smokers who wished to quit. Female ophthalmologists
      were more likely to undertake most aspects of smoking assessment and
      intervention. Only 18% of responders stated that their departments provide
      information about smoking for patients and 6% stated that support is available
      for patients wanting to quit smoking. CONCLUSION: The assessment of smoking
      status and provision of targeted support for smokers to quit could be
      substantially improved in UK ophthalmology departments. There is a need to
      introduce smoking cessation support into routine ophthalmic practice and provide
      the resources to support this.

PMID- 17016462
TI  - Surgical outcomes of intermittent exotropia associated with concomitant
      hypertropia including simulated superior oblique palsy after horizontal muscles
      surgery only.
AB  - PURPOSE: To investigate the clinical features and obtain guideline of treatment
      in intermittent exotropia associated with hypertropia including simulated
      superior oblique palsy. METHODS: We retrospectively reviewed the charts of 93
      patients of intermittent exotropia aligned with horizontal muscle surgery only,
      who showed hypertropia more than 2 PD in primary gaze before surgery and
      disappeared after surgery. They showed forveal extorsion and dysfunction of
      oblique muscles of 2+ or less and positive Bielschowsky head tilt test. The
      postoperative changes of deviation angle were analysed at postoperative 1 day, 6
      months, and 1 year. RESULTS: Average amount of distant horizontal deviation in
      primary gaze was 32.3+/-9.58 (25-53) PD, hypertropia was 3.50+/-2.52 (2-14) PD.
      Average vertical deviation of ipsilateral (hypertropic eye) side was 8.8+/-4.63
      PD and contralateral (hypotrophic eye) side was 4.0+/-4.77 PD in Bielschowsky
      head tilt test. Hypertropic eye was accorded with exotropic eye in 53.4%. After
      horizontal surgery, the amount of hypertropia was 1.2 PD at postoperative 1 day.
      On Bielschowsky head tilt test, hypertropia was almost eliminated showing 0.6 PD
      on the ipsilateral side and 0.2 PD on the contralateral eye at 1 month. This
      state was maintained up to postoperative 1 year. CONCLUSION: Small amount of
      hypertropia up to 14 PD in intermittent exotropia could be disappeared with
      horizontal muscle surgery only. However, careful examinations for head tilt
      history, fovea extorsion, oblique dysfunction, and Maddox rod test should be
      preceded to rule out true superior oblique palsy.

PMID- 17016463
TI  - Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular
      oedema.
AB  - AIMS: To assess the efficacy and safety of intravitreal triamcinolone in the
      treatment of postoperative cystoid macular oedema (CMO). METHODS: A retrospective
      case series review of 21 eyes (20 patients) that had an intravitreal injection of
      triamcinolone 4 mg for postoperative CMO. Diagnosis was confirmed by fundus
      fluorescein angiography and/or optical coherence tomography in all eyes. RESULTS:
      Mean age of patients was 71.1 years. CMO had developed following routine
      phacoemulsification cataract extraction (13 eyes), phacoemulsification cataract
      extraction complicated by posterior capsule tear and vitreous loss (two eyes),
      vitrectomy (three eyes), or planned combined phacoemulsification and vitrectomy
      (three eyes). Mean duration of CMO before triamcinolone injection was 4.9 months.
      Mean duration of follow-up was 7.4 months. Two eyes required a repeat injection.
      Mean logarithm of minimum angle of resolution (LogMAR) visual acuity (VA) before
      treatment was 0.53; at 1 month post injection, this increased significantly to
      0.33 (P<0.001). Improvement in VA was maintained throughout follow-up; at 6
      months or later, mean LogMAR VA was significantly better than baseline (0.33 vs
      0.53, P=0.02). At the latest review, 43% of eyes had improved Snellen VA by two
      or more lines and 86% by one or more lines compared to baseline. The remaining
      14% had reduced Snellen VA compared to baseline. In the post-injection period,
      33% of eyes developed an intraocular pressure of 22 mm Hg or higher and all
      responded well to short-term topical agents. There were no other post-injection
      complications. CONCLUSION: Intravitreal triamcinolone results in a rapid
      improvement in VA that may be sustained for more than 6 months.

PMID- 17016464
TI  - IOLMASTER vs theoretical calculation in eye.

PMID- 17016466
TI  - Reply to dr Haigis. Re: Errors in self-programming the Hoffer Q formula.

PMID- 17016467
TI  - Errors in self-programming the Hoffer Q formula.

PMID- 17016468
TI  - Progress and prospects: gene transfer into embryonic stem cells.
AB  - With the isolation of human embryonic stem cells (hESCs) in 1998 came the
      realization of a long-sought aspiration for an unlimited source of human tissue.
      The difficulty of differentiating ESCs to pure, clinically exploitable cell
      populations to treat genetic and degenerative diseases is being solved in part
      with the help of genetically modified cell lines. With progress in genome editing
      and somatic cell nuclear transfer, it is theoretically possible to obtain
      genetically repaired isogenic cells. Moreover, the prospect of being able to
      select, isolate and expand a single cell to a vast population of cells could
      achieve a unique level of quality control, until now unattainable in the field of
      gene therapy. Most of the tools necessary to develop these strategies already
      exist in the mouse ESC system. We review here the advances accomplished in those
      fields and present some possible applications to hESC research.

PMID- 17016469
TI  - Mechanisms of cell immortalization mediated by EB viral activation of telomerase
      in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast
      Asia. The disease is a poorly differentiated carcinoma without effective cure,
      and the mechanism underlying its development remains largely unknown. Of several
      factors identified in NPC aetiology in recent years, Epstein-Barr virus (EBV)
      infection has emerged to be most important. In almost all NPC cells, EBV uses
      several intracellular mechanisms to cause oncogenic evolution of the infected
      cells. One such mechanism by which EBV infection induces cellular immortalization
      is believed to be through the activation of telomerase, an enzyme that is
      normally repressed but becomes activated during cancer development. Studies show
      that greater than 85% of primary NPC display high telomerase activity by
      mechanisms involving EBV infection, consistent with the notion that EBV is
      commonly involved in inducing cell immortalization. More recently, different EBV
      proteins have been shown to activate or inhibit the human telomerase reverse
      transcriptase gene, by modulating intracellular signalling pathways. These
      findings suggest a new model with a number of challenges towards our
      understanding, molecular targeting and therapeutic intervention in NPC.

PMID- 17016470
TI  - High-density lipoproteins: an emerging target in the prevention of cardiovascular
      disease.
AB  - High-density lipoproteins (HDLs) have been well established to protect against
      the development of atherosclerotic cardiovascular disease. It has become apparent
      that in addition to the promotion of reverse cholesterol transport, HDLs possess
      a number of additional functional properties that may contribute to their
      beneficial influence on the arterial wall. A number of exciting therapeutic
      strategies have been developed that target HDL and its ability to protect against
      the development of atherosclerotic plaque. This paper will review how the
      promotion of the functional properties of HDL inhibits the formation of
      atherosclerotic plaque and stabilises lesions in patients with established
      disease.

PMID- 17016472
TI  - Clinical databases and biobanks for etiologic and therapeutic studies in
      rheumatoid arthritis.

PMID- 17016471
TI  - Repression of ergosterol level during oxidative stress by fission yeast F-box
      protein Pof14 independently of SCF.
AB  - We describe a new member of the F-box family, Pof14, which forms a canonical, F
      box dependent SCF (Skp1, Cullin, F-box protein) ubiquitin ligase complex. The
      Pof14 protein has intrinsic instability that is abolished by inactivation of its
      Skp1 interaction motif (the F-box), Skp1 or the proteasome, indicating that Pof14
      stability is controlled by an autocatalytic mechanism. Pof14 interacts with the
      squalene synthase Erg9, a key enzyme in ergosterol metabolism, in a membrane
      bound complex that does not contain the core SCF components. pof14 transcription
      is induced by hydrogen peroxide and requires the Pap1 transcription factor and
      the Sty1 MAP kinase. Pof14 binds to and decreases Erg9 activity in vitro and a
      pof14 deletion strain quickly loses viability in the presence of hydrogen
      peroxide due to its inability to repress ergosterol synthesis. A pof14 mutant
      lacking the F-box and an skp1-3 ts mutant behave as wild type in the presence of
      oxidant showing that Pof14 function is independent of SCF. This indicates that
      modulation of ergosterol level plays a key role in adaptation to oxidative
      stress.

PMID- 17016473
TI  - Epidural corticosteroid injections for sciatica: placebo effect, injection effect
      or anti-inflammatory effect?

PMID- 17016479
TI  - Early diagnosis of spondyloarthritis.
AB  - The term 'spondyloarthritis', which is preferred to 'spondyloarthropathy', refers
      to a group of similar diseases with distinct clinical features and a common
      genetic predisposition, rather than one disease with different clinical
      presentations. Mainly for clinical purposes, five disease subtypes are
      recognized: ankylosing spondylitis (AS), psoriatic spondyloarthritis, reactive
      spondyloarthritis, spondyloarthritis associated with inflammatory bowel disease,
      and undifferentiated spondyloarthritis. Irrespective of the disease subtype, the
      main clinical manifestations of spondyloarthritides are inflammatory back pain,
      peripheral arthritis, enthesitis and anterior uveitis, while other organ
      manifestations are rare. The need for a standardized, evidence-based approach to
      disease classification led to the development of the European Spondyloarthropathy
      Study Group preliminary criteria for spondyloarthritis in 1991, which confirmed
      the unifying concept of this group of diseases. In the past 10 years, the work of
      the European Spondyloarthropathy Study Group has been taken over by the
      Assessments in AS working group. There is still a considerable delay in diagnosis
      of AS and, because of the well-documented efficacy of anti-tumor-necrosis-factor
      therapy for all spondyloarthritis subtypes, diagnostic criteria (especially for
      early forms of spondyloarthritis) are needed. Diagnosis can be achieved by
      determination of the predominant clinical manifestation, and by the inclusion of
      sensitive diagnostic tools for early disease (such as HLA-B27 genotype and MRI)
      in the criteria set. In addition, because of the high incidence of back pain in
      affected individuals, the development of practical screening parameters that
      facilitate referral to the rheumatologist is important.

PMID- 17016480
TI  - A review of work-participation, cost-of-illness and cost-effectiveness studies in
      ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) can have important socioeconomic consequences for
      individual patients and for society, as symptoms usually appear in the third
      decade of life. When compared with those of the general population, employment
      rates for AS patients are significantly decreased in men, but not in women;
      however, both sexes experience increased AS-related (partial) work disability. In
      addition, changes in type of work, working hours, and the need for help might be
      required. AS-related sick leave in patients in paid work varies between 6.5 and
      18 days per patient per year. Between 15% and 20% of AS patients require help
      from relatives or friends to complete unpaid tasks. The majority of the direct
      health-care costs related to AS are incurred by hospitalizations, physiotherapy,
      informal care, and drugs. High disease activity and poor physical function are
      the most important factors associated with the total costs of AS. Cost
      effectiveness analyses for different AS therapies have shown variable results.
      The use of different methodologic approaches to assess the cost-effectiveness
      ratios makes the findings of such analyses difficult to compare with each other.
      This article examines the effect of AS on work participation, costs of illness
      and reviews cost-effectiveness analyses of AS treatments.

PMID- 17016481
TI  - Technology Insight: imaging of low back pain.
AB  - Chronic low back pain is a common condition that has significant economic
      consequences for affected patients and their communities. Despite the prevailing
      view that an anatomic diagnosis is often impossible, an origin for the pain can
      frequently be found if current diagnostic techniques are fully used. Such
      techniques include a mixture of noninvasive and invasive imaging. Prevalence data
      suggest that the intervertebral disc is one of the most common sources of back
      pain, accounting for around 40% of cases. The pathologic basis for discogenic low
      back pain might be full-thickness radial tears of the annulus fibrosus.
      Unfortunately, only MRI can image the internal morphology of the disc, and both
      CT and MRI lack the necessary specificity to validate this hypothesis. Many so
      called radiographic abnormalities seen on CT and MRI are commonly encountered in
      asymptomatic individuals. Invasive techniques such as joint injections, nerve
      blocks and provocative discography can show the connection between an abnormal
      image and the source of low back pain, but do have notable related risks. The
      development of a noninvasive, low-risk technique that can show this connection is
      desirable.

PMID- 17016482
TI  - Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus.
AB  - Survival of patients with systemic lupus erythematosus (SLE) has improved over
      the past decade, thanks to improved treatment of the disease, which now results
      in fewer fatal complications. This improvement has allowed physicians to focus
      their attention on the prevention of organ damage caused by this chronic,
      inflammatory disease, and by the medications used to control the disease.
      Osteoporosis is common in SLE patients; risk factors for osteoporosis include
      prolonged use of glucocorticoids, cyclophosphamide and possibly gonadotropin
      releasing-hormone agonists. In premenopausal women with SLE, inflammation or SLE
      related medications can increase bone turnover, which eventually weakens bone
      architecture, then reduces bone strength and increases the risk of fracture.
      Prevention and treatment of osteoporosis in SLE patients should entail a
      multifaceted approach. Levels of calcium, vitamin D and homocysteine should be
      evaluated, and age-appropriate supplementation instituted. The bone loss that
      results from systemic inflammation should be treated by reduction of the
      inflammation with glucocorticoids, potent anti-inflammatory agents or
      antiresorptive agents. The efficacy of this therapy can be monitored using bone
      mineral density scans. This Review briefly discusses the pathophysiology of the
      localized and generalized osteoporosis and osteonecrosis in SLE patients and
      recommends therapies to both prevent and treat these unfortunate complications of
      this disease.

PMID- 17016483
TI  - Lymphoma in a patient with systemic lupus erythematosus.
AB  - BACKGROUND: A 40-year-old woman with a 10-year history of systemic lupus
      erythematosus (SLE) presented with fever, lymphadenopathy and fatigue. Before
      that time, her SLE symptoms had been controlled with hydroxychloroquine, NSAIDs,
      and an occasional short course of moderate-dose prednisone. Two months before
      presentation, she experienced fevers ranging from 38.3 to 39.7 degrees C, but she
      had no specific symptoms that suggested local infection. INVESTIGATIONS: Physical
      examination, multiple blood cultures, and laboratory investigations that included
      the following tests: hemoglobin concentration; erythrocyte sedimentation rate; C
      reactive protein level; serum lactate dehydrogenase level; aspartate
      aminotransferase level; alanine aminotransferase level; serum complement C3 and
      C4 levels; white-blood-cell count; platelet count; urinalysis; serum creatinine
      level; CT of the chest and abdomen; bone-marrow biopsy; serum electrophoresis;
      and tests for Epstein-Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C
      virus, HIV-1, antinuclear antibodies, antibodies to Smith antigen, antibodies to
      double-stranded DNA, and antibodies to Ro and La. DIAGNOSIS: Stage IVB diffuse
      large B-cell lymphoma with marrow and liver involvement concurrent with SLE.
      MANAGEMENT: The patient promptly underwent chemotherapy, receiving three courses
      of 3 mg/m(2) vindesine on day 1, 1,500 mg/m(2) cyclophosphamide and 80 mg/m(2)
      doxorubicin on day 2, and 50 mg/m(2) prednisolone on days 1-5.

PMID- 17016484
TI  - Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging
      vs X-ray mammography of women at a high familial risk of breast cancer.
AB  - Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool
      for screening women who are at high familial risk of breast cancer. Our aim in
      this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE
      MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS
      study and screened with both CE MRI and mammography resulting in 1881 screens and
      1-7 individual annual screening events. Women aged 35-49 years at high risk of
      breast cancer, either because they have a strong family history of breast cancer
      or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of
      having inherited such a mutation, were recruited from 22 centres and offered
      annual MRI and XRM for between 2 and 7 years. Information on the number and type
      of further investigations was collected and specifically calculated unit costs
      were used to calculate the incremental cost per cancer detected. The numbers of
      cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and
      CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women
      having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding
      numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the
      incremental cost per cancer detected with CE MRI and mammography combined was
      pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were
      considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and
      pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive
      to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI
      might be a cost-effective screening modality for women at high risk, particularly
      for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of
      screening on mortality and health-related quality of life.

PMID- 17016485
TI  - Ten-year follow-up results of a randomised controlled study comparing level-I vs
      level-III axillary lymph node dissection for primary breast cancer.
AB  - The most appropriate level of axillary dissection for breast cancer remains
      unclear. The present randomised study compared the treatment results of level-I
      vs level-III dissection in T1/2/3 and N0/1a/1b (1987 UICC classification) breast
      cancer without distant metastasis. Between 1995 and 1997, 522 patients were
      enrolled, and 514 were eligible. They were stratified into breast-conserving
      surgery or mastectomy, and then further stratified into level-III dissection
      (group-A, n=258) or level-I dissection (group-B, n=256). All patients were given
      oral 5-fluorouracil at 200 mg day-1 and tamoxifen at 20 mg day-1, daily for 2
      years. Group-A resulted in a significantly longer operation time (77.0 vs 60.5
      min, P<0.0001) and significantly larger blood loss (62.1 vs 48.1 ml, P<0.0001)
      than group-B, but in no significant differences in the frequencies of arm oedema
      and shoulder disturbance. Group-A resulted in a significantly larger number of
      dissected nodes than group-B (18.7 vs 14.8, P<0.0001), but in no differences in
      the number of involved nodes (1.54 vs 1.44). There were no significant
      differences in the 10-year overall and disease-free survival rates: 89.6 and
      76.6% for group-A vs 87.8 and 74.1% for group-B, respectively. In conclusion,
      level-III dissection resulted in a longer operation time and greater blood loss
      than level-I, but did not improve the survival rate. Level-III dissection is not
      a recommended surgery for T1-3/N0-1b breast cancer.

PMID- 17016486
TI  - Evaluation of models to predict BRCA germline mutations.
AB  - The selection of candidates for BRCA germline mutation testing is an important
      clinical issue yet it remains a significant challenge. A number of risk
      prediction models have been developed to assist in pretest counselling. We have
      evaluated the performance and the inter-rater reliability of four of these models
      (BRCAPRO, Manchester, Penn and the Myriad-Frank). The four risk assessment models
      were applied to 380 pedigrees of families who had undergone BRCA1/2 mutation
      analysis. Sensitivity, specificity, positive and negative predictive values,
      likelihood ratios and area under the receiver operator characteristic (ROC) curve
      were calculated for each model. Using a greater than 10% probability threshold,
      the likelihood that a BRCA test result was positive in a mutation carrier
      compared to the likelihood that the same result would be expected in an
      individual without a BRCA mutation was 2.10 (95% confidence interval (CI) 1.66
      2.67) for Penn, 1.74 (95% CI 1.48-2.04) for Myriad, 1.35 (95% CI 1.19-1.53) for
      Manchester and 1.68 (95% CI 1.39-2.03) for BRCAPRO. Application of these models,
      therefore, did not rule in BRCA mutation carrier status. Similar trends were
      observed for separate BRCA1/2 performance measures except BRCA2 assessment in the
      Penn model where the positive likelihood ratio was 5.93. The area under the ROC
      curve for each model was close to 0.75. In conclusion, the four models had very
      little impact on the pre-test probability of disease; there were significant
      clinical barriers to using some models and risk estimates varied between experts.
      Use of models for predicting BRCA mutation status is not currently justified for
      populations such as that evaluated in the current study.

PMID- 17016487
TI  - The impact of surgically induced ischaemia on protein levels in patients
      undergoing rectal cancer surgery.
AB  - The goal of targeted therapy has driven a search for markers of prognosis and
      response to adjuvant therapy. The surgical resection of a solid tumour induces
      tissue ischaemia and acidosis, both potent mediators of gene expression. This
      study investigated the impact of colorectal cancer (CRC) surgery on prognostic
      and predictive marker levels. Tumour expression of thymidylate synthase,
      thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF),
      carbonic anhydrase-9, hypoxia inducible factor-1alpha, and glucose transporter-1
      (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral
      imaging of tissue sections stained by immunohistochemistry provided quantitative
      data. Surgery altered thymidylate synthase protein expression (P=0.02), and this
      correlated with the change in the proliferation marker cyclin A. The expression
      of hypoxia inducible factor-1alpha, VEGF, and GLUT-1 proteins was also different
      following surgery. Colorectal cancer surgery significantly impacts on
      intratumoral gene expression, suggesting archival specimens may not accurately
      reflect in situ marker levels. Although rectal cancer was the studied model, the
      results may be applicable to any solid tumour undergoing extirpation in which
      molecular markers have been proposed to guide patient therapy.

PMID- 17016488
TI  - High mortality from neo-adjuvant chemo-radiotherapy for rectal cancer needs to be
      evaluated against the alternative of adjuvant therapy.

PMID- 17016490
TI  - The International Standards for Neurological Classification of Spinal Cord
      Injury: reliability of data when applied to children and youths.
AB  - STUDY DESIGN: Intra-rater reliability study, cross-sectional design. OBJECTIVES:
      To determine reliability of the International Standards for Neurological
      Classification of Spinal Cord Injury (ISCSCI) motor and sensory exam in children.
      SETTING: Nonprofit pediatric hospital. METHODS: In all, 74 subjects had two
      trials of the motor and sensory exams. Intraclass correlation coefficients (ICC),
      95% confidence intervals (CI) were generated for total motor (TM), pin prick (PP)
      and light touch (LT) scores for the entire sample, four age groups, severity and
      type of injury. Coefficients >0.90=high reliability; 0.75-0.90=moderate
      reliability and <0.75=inadequate reliability. RESULTS: Children <four years (N=7)
      were unable to participate in the exams. TM ICC, CI=0.888, 0.821-0.93 (N=73); PP
      ICC, CI=0.975, 0.96-0.98 (N=67) and LT ICC, CI=0.974, 0.974-0.985 (N=68). When
      age was considered, 4-5 year: TM ICC, CI=0.917, 0.69-0.98 (N=11), PP=0.912, 0.49
      0.985 (N=7), LT=0.948, 0.63-0.993 (N=6); for 6-11 year: TM ICC, CI=0.711, 0.226
      0.892 (N=18), PP=0.952, 0.867-0.983 (M=17), LT=0.952, 0.867-0.983 (N=17); for 12
      15 year: TM ICC, CI=0.893, 0.723-0.959 (N=19), PP=0.982, 0.953-0.993 (N=19),
      LT=0.982, 0.953-0.993 (N=19); for 16-21 year: TM ICC, CI=0.912, 0.80-0.961
      (N=25), PP=0.98, 0.954-0.991 (N=25), LT=0.98, 0.954-0.991 (N=25). ICC for
      severity and type of injury >0.90 except for TM in complete injuries (0.808).
      CONCLUSION: The ISCSCI exams may have poor utility in children under 4 years.
      While reliability values for the motor and sensory exams met or exceeded
      recommended values, wide CI suggest poor precision of the motor exam in children
      under 15 years of age and sensory exams in children under 5 years.

PMID- 17016491
TI  - Re: Ditunno JF, Little JW, Tessler A, Burns AS. Spinal shock revisited: a four
      phase model. Spinal Cord 2004; 42: 383-395.

PMID- 17016492
TI  - Long-term effects of spinal cord injury on sexual function in men: implications
      for neuroplasticity.
AB  - STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Elicit specific information
      about sexual function from men with spinal cord injuries (SCI). SETTING: World
      wide web. METHODS: Individuals 18 years or older living with SCI obtained a pass
      code to enter a secure website and then answered survey questions. RESULTS: The
      presence of genital sensation was positively correlated with the ability to feel
      a build up of sexual tension in the body during sexual stimulation and in the
      feeling that mental arousal translates to the genitals as physical sensation.
      There was an inverse relationship between developing new areas of arousal above
      the level of lesion and not having sensation or movement below the lesion. A
      positive relationship existed between the occurrence of spasticity during sexual
      activity and erectile ability. Roughly 60% of the subjects had tried some type of
      erection enhancing method. Only 48% had successfully achieved ejaculation
      postinjury and the most commonly used methods were hand stimulation, sexual
      intercourse, and vibrostimulation. The most commonly cited reasons for trying to
      ejaculate were for pleasure and for sexual intimacy. Less than half reported
      having experienced orgasm postinjury and this was influenced by the length of
      time postinjury and sacral sparing. CONCLUSION: SCI not only impairs male
      erectile function and ejaculatory ability, but also alters sexual arousal in a
      manner suggestive of neuroplasticity. More research needs to be pursued in a
      manner encompassing all aspects of sexual function.

PMID- 17016493
TI  - Spontaneous spinal epidural hematoma in a 4-month-old infant.
AB  - STUDY DESIGN: A case report and a review of literature. OBJECTIVES: To present
      the first youngest infant of a 4-month-old boy with spontaneous spinal epidural
      hematoma in cervicothoracic spine. SETTING: National Cheng Kung University
      Hospital, Tainan, Taiwan. METHODS: A 4-month-old boy who initially presented with
      irritable crying, neck stiffness, and fever followed by progressive
      quadriparesis. Magnetic resonance imaging (MRI) of the spine disclosed a space
      occupying lesion on the right posterior-lateral aspect of the cervicothoracic
      spinal canal. Laminectomy with reconstruction in situ from C4 to T4 was performed
      5 days after the onset of symptoms. RESULTS: The boy had gradual improvement of
      his neurological status. Follow-up visit 1 year later, the infant's growth and
      development was within normal limit without any neurological deficits; his repeat
      MRI showed complete fusion of each implanted lamina and well expansion of the
      spinal cord. CONCLUSIONS: Prompt surgical decompression is valuable, irrespective
      of the time interval between symptom onset and operation in infant.

PMID- 17016494
TI  - Effects of nitric oxide synthase inhibition with or without cyclooxygenase-2
      inhibition on resting haemodynamics and responses to exendin-4.
AB  - BACKGROUND AND PURPOSE: Interactions between the NO system and the cyclooxygenase
      systems may be important in cardiovascular regulation. Here we measured the
      effects of acute cyclooxygenase-2 inhibition (with parecoxib), alone and in
      combination with NOS inhibition (with NG-nitro-L-arginine methyl ester (L-NAME)),
      on resting cardiovascular variables and on responses to the glucagon-like peptide
      1 agonist, exendin-4, which causes regionally-selective vasoconstriction and
      vasodilatation. EXPERIMENTAL APPROACH: Rats were instrumented with flow probes
      and intravascular catheters to measure regional haemodynamics in the conscious,
      freely moving state. L-NAME was administered as a primed infusion 180 min after
      administration of parecoxib or vehicle, and exendin-4 was given 60 min after the
      onset of L-NAME infusion. KEY RESULTS: Parecoxib had no effect on resting
      cardiovascular variables or on responses to L-NAME. Exendin-4 caused a pressor
      response accompanied by tachycardia, mesenteric vasoconstriction and hindquarters
      vasodilatation. Parecoxib did not affect haemodynamic responses to exendin-4, but
      L-NAME inhibited its hindquarters vasodilator and tachycardic effects. When
      combined, L-NAME and parecoxib almost abolished the hindquarters vasodilatation
      while enhancing the pressor response. CONCLUSIONS AND IMPLICATIONS:
      Cyclooxygenase-2-derived products do not affect basal haemodynamic status in
      conscious normotensive rats, or influence the NO system acutely. The inhibitory
      effects of L-NAME on the hindquarters vasodilator and tachycardic effects of
      exendin-4 are consistent with a previous study that showed those events to be
      beta-adrenoceptor mediated. The additional effect of parecoxib on responses to
      exendin-4 in the presence of L-NAME, is consistent with other evidence for
      enhanced involvement of vasodilator prostanoids when NO production is reduced.

PMID- 17016495
TI  - Sensitivity of glycogen phosphorylase isoforms to indole site inhibitors is
      markedly dependent on the activation state of the enzyme.
AB  - BACKGROUND AND PURPOSE: Inhibition of hepatic glycogen phosphorylase is a
      potential treatment for glycaemic control in type 2 diabetes. Selective
      inhibition of the liver phosphorylase isoform could minimize adverse effects in
      other tissues. We investigated the potential selectivity of two indole site
      phosphorylase inhibitors, GPi688 and GPi819. EXPERIMENTAL APPROACH: The activity
      of glycogen phosphorylase was modulated using the allosteric effectors glucose or
      caffeine to promote the less active T state, and AMP to promote the more active R
      state. In vitro potency of indole site inhibitors against liver and muscle
      glycogen phosphorylase a was examined at different effector concentrations using
      purified recombinant enzymes. The potency of GPi819 was compared with its in vivo
      efficacy at raising glycogen concentrations in liver and muscle of Zucker (fa/fa)
      rats. KEY RESULTS: In vitro potency of indole site inhibitors depended upon the
      activity state of phosphorylase a. Both inhibitors showed selectivity for liver
      phosphorylase a when the isoform specific activities were equal. After 5 days
      dosing of GPi819 (37.5 micromol kg(-1)), where free compound levels in plasma and
      tissue were at steady state, glycogen elevation was 1.5-fold greater in soleus
      muscle than in liver (P < 0.05). CONCLUSIONS AND IMPLICATIONS: The in vivo
      selectivity of GPi819 did not match that seen in vitro when the specific
      activities of phosphorylase a isoforms are equal. This suggests T state promoters
      may be important physiological regulators in skeletal muscle. The greater
      efficacy of indole site inhibitors in skeletal muscle has implications for the
      overall safety profile of such drugs.

PMID- 17016497
TI  - Tamoxifen dilates porcine coronary arteries: roles for nitric oxide and ouabain
      sensitive mechanisms.
AB  - BACKGROUND AND PURPOSE: Experiments were designed to determine the mechanism of
      the relaxation induced by tamoxifen in porcine coronary arteries at the tissue,
      cellular and molecular levels. EXPERIMENTAL APPROACH: Porcine left circumflex
      coronary arteries were isolated and isometric tension was measured. [Ca2+]i in
      native endothelial cells of intact arteries was determined by a calcium
      fluorescence imaging technique and eNOS ser1177 phosphorylation was assayed by
      Western blotting. KEY RESULTS: Tamoxifen induced an endothelium-dependent
      relaxation that was antagonized by ICI 182,780 and abolished by NG-nitro-L
      arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one
      (ODQ). L-Arginine reversed the effect of L-NAME while indomethacin was without
      effect. Tamoxifen-induced relaxation was attenuated by charybdotoxin (CTX) plus
      apamin, ouabain or by incubation in a K+ -free solution. Moreover, tamoxifen
      triggered extracellular Ca2+ -dependent increases in endothelial [Ca2+]i and this
      effect was abolished by ICI 182,780. Endothelium-independent relaxation to sodium
      nitroprusside was also inhibited by ouabain or in a K+ -free solution.
      Furthermore, tamoxifen increased endothelial nitric oxide synthase (eNOS)
      phosphorylation at Ser-1177 and ICI 182,780 prevented this effect. CONCLUSIONS
      AND IMPLICATIONS: The present results suggest that tamoxifen mainly induces
      endothelium-dependent relaxation and that endothelial nitric oxide (NO) is the
      primary mediator of this effect. NO-dependent responses may result from elevated
      [Ca2+]i in endothelial cells; an effect abolished by ICI 182,780. NO activates
      Na+/K+ -ATPase in vascular smooth muscle, leading to relaxation. These results
      suggest that tamoxifen is able to modulate eNOS phosphorylation directly.

PMID- 17016496
TI  - Prostaglandin E2 receptor distribution and function in the gastrointestinal
      tract.
AB  - Prostaglandin E2 (PGE2) is one of the most important biologically active
      prostanoids found throughout the gastrointestinal tract. Despite the fact that
      PGE2 regulates many physiological functions of the gut including mucosal
      protection, gastrointestinal secretion and motility, it is implicated in the
      pathophysiology of inflammatory bowel diseases (IBD) and colorectal neoplasia.
      The varied biological functions exerted by PGE2 are through the pharmacologically
      distinct, G-protein coupled plasma membrane receptors termed EP receptors.
      Disruptions of various prostanoid receptor genes have helped in unravelling the
      physiological functions of these receptors. To date, all four subtypes of EP
      receptors have been individually knocked out in mice and various phenotypes have
      been reported for each subtype. Similarly, in vitro and in vivo studies using EP
      receptor agonists and antagonists have helped in uncoupling the diverse functions
      of PGE2 signalling involving distinct EP receptors in the gut. In this review, we
      will summarize and conceptualize the salient features of EP receptor subtypes,
      their regional functions in the gut and how expressions of EP receptors are
      altered during disease states.

PMID- 17016498
TI  - Reciprocal regulation of human soluble and particulate guanylate cyclases in
      vivo.
AB  - BACKGROUND & PURPOSE: We demonstrated previously that reciprocal regulation of
      soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic
      peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we
      investigated whether such an interaction contributes to vascular homeostasis in
      mice and humans in vivo. EXPERIMENTAL APPROACH: Mean arterial blood pressure
      (MABP) changes in anaesthetized mice were monitored in response to i.v.
      administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT),
      endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout
      mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25,
      50, 100, 200 pmol min(-1)) in the absence and presence of the NOS inhibitor NG
      methyl-L-arginine (L-NMA; 4 micromol min(-1)) and the control constrictor
      noradrenaline (240 pmol min(-1)) was assessed in healthy volunteers. KEY RESULTS:
      Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP)
      produced dose-dependent reductions in MABP in WT animals that were significantly
      enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent
      reduction in MABP that was significantly greater than that in WT mice.
      Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT,
      eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance
      vasculature that was significantly greater in individuals lacking endothelium
      derived NO (i.e. L-NMA treated). CONCLUSIONS & IMPLICATIONS: These data
      demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to
      regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These
      findings have implications for understanding the link between natriuretic peptide
      activity and cardiovascular risk.

PMID- 17016499
TI  - The actions of azelnidipine, a dihydropyridine-derivative Ca antagonist, on
      voltage-dependent Ba2+ currents in guinea-pig vascular smooth muscle.
AB  - BACKGROUND AND PURPOSE: Although azelnidipine is used clinically to treat
      hypertension its effects on its target cells, Ca2+ channels, in smooth muscle
      have not been elucidated. Therefore, its effects on spontaneous contractions and
      voltage-dependent L-type Ca2+ channels were investigated in guinea-pig portal
      vein. EXPERIMENTAL APPROACH: The inhibitory potency of azelnidipine on
      spontaneous contractions in guinea-pig portal vein was compared with those of
      other dihydropyridine (DHP)-derived Ca antagonists (amlodipine and nifedipine) by
      recording tension. Also its effects on voltage-dependent nifedipine-sensitive
      inward Ba2+ currents (IBa) in smooth muscle cells dispersed from guinea-pig
      portal vein were investigated by use of a conventional whole-cell patch-clamp
      technique. KEY RESULTS: Spontaneous contractions in guinea-pig portal vein were
      reduced by all of the Ca antagonists (azelnidipine, Ki = 153 nM; amlodipine, Ki =
      16 nM; nifedipine, Ki = 7 nM). In the whole-cell experiments, azelnidipine
      inhibited the peak amplitude of IBa in a concentration- and voltage-dependent
      manner (-60 mV, Ki = 282 nM; -90 mV, Ki = 2 microM) and shifted the steady-state
      inactivation curve of IBa to the left at -90 mV by 16 mV. The inhibitory effects
      of azelnidipine on IBa persisted after 7 min washout at -60 mV. In contrast, IBa
      gradually recovered after being inhibited by amlodipine, but did not return to
      control levels. Both azelnidipine and amlodipine caused a resting block of IBa at
      -90 mV. Only nifedipine appeared to interact competitively with S(-)-Bay K 8644.
      CONCLUSIONS AND IMPLICATIONS: These results suggest that azelnidipine induces
      long-lasting vascular relaxation by inhibiting voltage-dependent L-type Ca2+
      channels in vascular smooth muscle.

PMID- 17016500
TI  - AM-36 modulates the neutrophil inflammatory response and reduces breakdown of the
      blood brain barrier after endothelin-1 induced focal brain ischaemia.
AB  - BACKGROUND AND PURPOSE: Following transient focal stroke, rapid accumulation and
      activation of neutrophils in the ischaemic region is deleterious due to release
      of reactive oxygen species and myeloperoxidase (MPO). The purpose of this study
      was to examine whether AM-36, both a Na+ channel blocker and an antioxidant,
      afforded neuroprotection by modulating neutrophil accumulation into brain,
      following endothelin-1 (ET-1) induced middle cerebral artery occlusion (MCAo) in
      conscious rats. EXPERIMENTAL APPROACH: AM-36 was administered at 3 and 24 h after
      ET-1-induced MCAo. Functional recovery was determined using grid-walking and
      cylinder tests. Image analysis of brain sections was used to determine infarct
      volume. The effect of AM-36 on neutrophil infiltration and their interaction with
      macrophages was examined in rats at 48 h following MCAo by both an MPO assay and
      double-label immunofluorescence. Blood brain barrier (BBB) breakdown was measured
      by the area stained by intravenous Evans Blue. KEY RESULTS: AM-36 reduced
      functional deficits in both tests such that no difference existed from pre
      ischaemic values at 48 h. Neutrophil infiltration, assessed by MPO activity, and
      infarct volume were significantly reduced following AM-36 administration by 54
      and 60% respectively. Similarly, immunofluorescence revealed that AM-36 reduced
      neutrophil infiltration by approximately 50% in selected brain regions, when
      compared to controls, and also modulated macrophage phagocytosis of neutrophils.
      Breakdown of the BBB was significantly reduced by 60% following AM-36 treatment.
      CONCLUSIONS AND IMPLICATIONS: These findings suggest that AM-36 can directly
      modulate the neutrophil inflammatory response and reduce BBB breakdown following
      MCAo.

PMID- 17016501
TI  - Blood-brain distribution of morphine-6-glucuronide in sheep.
AB  - BACKGROUND AND PURPOSE: At present there are few data regarding the rate and
      extent of brain-blood partitioning of the opioid active metabolite of morphine,
      morphine-6-glucuronide (M6G). In this study the cerebral kinetics of M6G were
      determined, after a short-term intravenous infusion, in chronically instrumented
      conscious sheep. EXPERIMENTAL APPROACH: Five sheep received an intravenous
      infusion of M6G 2.2 mg kg(-1) over a four-minute period. Non-linear mixed-effects
      analysis, with hybrid physiologically based kinetic models, was used to estimate
      cerebral kinetics from the arterio-sagittal sinus concentration gradients and
      cerebral blood flow measurements. KEY RESULTS: A membrane limited model was
      selected as the final model. The blood-brain equilibration of M6G was relatively
      slow (time to reach 50% equilibration of the deep compartment 5.8 min), with low
      membrane permeability (PS, population mean, 2.5 ml min(-1)) from the initial
      compartment (V1, 13.7 ml) to a small deep distribution volume (V2) of 18.4 ml.
      There was some between-animal variability (%CV) in the initial distribution
      volume (29%), but this was not identified for PS or V2. CONCLUSION AND
      IMPLICATIONS: Pharmacokinetic modelling of M6G showed a delayed equilibration
      between brain and blood of a nature that is primarily limited by permeability
      across the blood-brain-barrier, in accordance with its physico-chemical
      properties.

PMID- 17016502
TI  - Inhalation of activated protein C inhibits endotoxin-induced pulmonary
      inflammation in mice independent of neutrophil recruitment.
AB  - BACKGROUND AND PURPOSE: Intravenous administration of recombinant human activated
      protein C (rhAPC) is known to reduce lipopolysaccharide (LPS)-induced pulmonary
      inflammation by attenuating neutrophil chemotaxis towards the alveolar
      compartment. Ideally, one would administer rhAPC in pulmonary inflammation at the
      site of infection to minimize the risk of systemic bleeding complications. In
      this study, we therefore assessed the effect of inhaled rhAPC in a murine model
      of acute lung injury. EXPERIMENTAL APPROACH: Mice were exposed to LPS (0.5 mg kg(
      1): intranasally) to induce acute lung injury. 30 minutes before and 3 hours
      after LPS exposure mice were subjected to vehicle or rhAPC inhalation (25 or 100
      microg per mouse in each nebulization). In order to establish whether rhAPC
      inhalation affects neutrophil recruitment, neutrophil migration was determined in
      vitro using a trans-well migration assay. KEY RESULTS: rhAPC inhalation dose
      dependently decreased LPS-induced coagulation and inflammation markers in
      bronchoalveolar lavage fluid (BALF), reduced protein leakage into the alveolar
      space and improved lung function. In contrast, rhAPC did not prevent LPS-induced
      neutrophil recruitment into the alveolar space. Neutrophil migration in vitro
      towards FCS or interleukin (IL)-8 was significantly inhibited by pretreatment
      with rhAPC (0.01-10 microg ml(-1)], whereas rhAPC (10 microg ml(-1)) added to the
      chemoattractant (modelling for topical rhAPC administration) did not affect
      neutrophil migration towards FCS or IL-8. CONCLUSIONS AND IMPLICATIONS: rhAPC
      inhalation significantly diminished LPS-induced pulmonary inflammation. The
      benefit of inhaled rhAPC appeared not to involve attenuation of neutrophil
      recruitment, in contrast to its effects after intravenous administration.

PMID- 17016503
TI  - Modulation of the function of presynaptic alpha7 and non-alpha7 nicotinic
      receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse
      brain.
AB  - BACKGROUND AND PURPOSE: Two metabolites of tryptophan, 5-hydroxyindole and
      kynurenic acid (kynurenate) affect the function of alpha7 nicotinic acetylcholine
      receptors (nAChRs), as measured by electrophysiological and Ca2+ fluorescence
      techniques. To better understand the modulations by 5-hydroxyindole and
      kynurenate of the function of nAChR subtypes, we compared the effects of 5
      hydroxyindole and kynurenate on the release of various transmitters evoked by
      nAChR activation. EXPERIMENTAL APPROACH: The function of alpha7nAChRs located on
      glutamatergic terminals was investigated by monitoring the release of [3H]D
      aspartate or of endogenous glutamate from neocortical synaptosomes. We also
      comparatively considered non-alpha7 release-enhancing nAChRs localized on
      hippocampal noradrenergic or cholinergic terminals, as well as on striatal
      dopaminergic terminals. KEY RESULTS: Epibatidine or nicotine, inactive on their
      own on basal release, enhanced [3H]D- aspartate and glutamate efflux in presence
      of 5-hydroxyindole. The release evoked by nicotine plus 5-hydroxyindole was
      abolished by methyllycaconitine or alpha-bungarotoxin. Presynaptic nAChRs
      mediating the release of [3H]noradrenaline ([3H]NA), [3H]dopamine ([3H]DA), or
      [3H]ACh were inhibited by 5-OHi. The alpha7nAChR-mediated release of [3H]D
      aspartate was reduced by kynurenate at concentrations unable to affect the non
      alpha7 receptor-mediated release of tritiated NA, DA or ACh. CONCLUSIONS AND
      IMPLICATIONS: (i) 5-hydroxyindole permits selective activation of alpha7nAChRs
      mediating glutamate release; (ii) kynurenate down-regulates the permissive role
      of 5-hydroxyindole on alpha7nAChR activation; (iii) the non-alpha7nAChRs
      mediating release of NA, DA or ACh can be inhibited by 5-hydroxyindole, but not
      by kynurenate. These findings suggest up the possibility of developing novel
      drugs able to modulate selectively the cholinergic-glutamatergic transmission.

PMID- 17016505
TI  - Cardiovascular responses to combined treatment with selective monoamine oxidase
      type B inhibitors and L-DOPA in the rat.
AB  - BACKGROUND AND PURPOSE: Postural hypotension is a common side-effect of L-DOPA
      treatment of Parkinson's disease, and may be potentiated when L-DOPA is combined
      with selegiline, a selective inhibitor of monoamine oxidase B (MAO-B). Rasagiline
      is a new, potent and selective MAO-B inhibitor, which does not possess the
      sympathomimetic effects of selegiline. We have studied the effects of these
      selective MAO inhibitors, L-DOPA and dopamine on the cardiovascular system of the
      rat. EXPERIMENTAL APPROACH: Blood pressure and heart rate was measured in
      conscious rats following acute or chronic administration of rasagiline,
      selegiline and L-DOPA, by comparison with the selective MAO-A inhibitor
      clorgyline, or the MAO-A/B inhibitor tranylcypromine. Cardiovascular responses,
      catecholamine release, and modification of pressor response to dopamine were
      studied in pithed rats. KEY RESULTS: In conscious rats neither rasagiline nor
      selegiline caused significant potentiation of the effects of L-DOPA (50, 100, 150
      mg.kg(-1)) on blood pressure or heart rate at doses which selectively inhibited
      MAO-B, but L-DOPA responses were potentiated by clorgyline and tranylcypromine.
      In rats treated twice daily for 8 days with L-DOPA and carbidopa, selegiline (5
      mg.kg(-1)) but not rasagiline (0.2 mg.kg(-1)) caused a significant hypotensive
      response to L-DOPA and carbidopa, although both drugs caused similar inhibition
      of MAO-A and MAO-B. In pithed rats, selegiline but not rasagiline increased
      catecholamine release and heart rate, and potentiated dopamine pressor response
      at MAO-B selective dose. CONCLUSIONS AND IMPLICATIONS: The different responses to
      the two MAO-B inhibitors may be explained by the amine releasing effect of
      amphetamine metabolites formed from selegiline.

PMID- 17016504
TI  - Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine
      networks in vivo.
AB  - BACKGROUND AND PURPOSE: The chemokine receptor CCR1 is a potential target for the
      treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in
      experimental arthritis and the underlying mechanisms, we used J-113863, a non
      peptide antagonist of the mouse receptor. EXPERIMENTAL APPROACH: Compound J
      113863 was tested in collagen-induced arthritis (CIA) and three models of acute
      inflammation; Staphylococcus enterotoxin B (SEB)-induced interleukin-2 (IL-2),
      delayed-type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)
      induced tumour necrosis factoralpha (TNFalpha) production. In the LPS model, CCR1
      knockout, adrenalectomised, or IL-10-depleted mice were also used. Production of
      TNFalpha by mouse macrophages and human synovial membrane samples in vitro were
      also studied. KEY RESULTS: Treatment of arthritic mice with J-113863 improved paw
      inflammation and joint damage, and dramatically decreased cell infiltration into
      joints. The compound did not inhibit IL-2 or DTH, but reduced plasma TNFalpha
      levels in LPS-treated mice. Surprisingly, CCR1 knockout mice produced more
      TNFalpha than controls in response to LPS, and J-113863 decreased TNFalpha also
      in CCR1 null mice, indicating that its effect was unrelated to CCR1.
      Adrenalectomy or neutralisation of IL-10 did not prevent inhibition of TNFalpha
      production by J-113863. The compound did not inhibit mouse TNFalpha in vitro, but
      did induce a trend towards increased TNFalpha release in cells from synovial
      membranes of rheumatoid arthritis patients. CONCLUSIONS AND IMPLICATIONS: CCR1
      blockade improves the development of CIA, probably via inhibition of inflammatory
      cell recruitment. However, results from both CCR1-deficient mice and human
      synovial membranes suggest that, in some experimental settings, blocking CCR1
      could enhance TNF production.

PMID- 17016506
TI  - What is the significance of vascular hydrogen sulphide (H2S)?
AB  - The important role of nitric oxide (NO) in the regulation of vascular tone has
      been well studied. By contrast, the vascular significance of another gaseous
      mediator, hydrogen sulphide (H2S), is still poorly understood. A study published
      in this issue of the British Journal of Pharmacology now provides evidence that
      in addition to the vasorelaxant effects of H2S reported in vitro, low
      concentrations of H2S also cause arterial vasoconstriction, reverse NO-mediated
      vasorelaxation and cause an NO-dependent pressor effect in vivo. This commentary
      discusses the implications and questions raised by these results.

PMID- 17016507
TI  - Regulation of vascular nitric oxide in vitro and in vivo; a new role for
      endogenous hydrogen sulphide?
AB  - BACKGROUND AND PURPOSE: The aim of these experiments was to evaluate the
      significance of the chemical reaction between hydrogen sulphide (H2S) and nitric
      oxide (NO) for the control of vascular tone. EXPERIMENTAL APPROACH: The effect of
      sodium hydrosulphide (NaHS; H2S donor) and a range of NO donors, such as sodium
      nitroprusside (SNP), either alone or together, was determined using phenylephrine
      (PE)-precontracted rat aortic rings and on the blood pressure of anaesthetised
      rats. KEY RESULTS: Mixing NaHS with NO donors inhibited the vasorelaxant effect
      of NO both in vitro and in vivo. Low concentrations of NaHS or H2S gas in
      solution reversed the relaxant effect of acetylcholine (ACh, 400 nM) and
      histamine (100 microM) but not isoprenaline (400 nM). The effect of NaHS on the
      ACh response was antagonized by CuSO(4) (200 nM) but was unaffected by
      glibenclamide (10 microM). In contrast, high concentrations of NaHS (200-1600
      microM) relaxed aortic rings directly, an effect reduced by glibenclamide but
      unaffected by CuSO4. Intravenous infusion of a low concentration of NaHS (10
      micromol kg(-1) min(-1)) into the anaesthetized rat significantly increased mean
      arterial blood pressure. L-NAME (25 mg kg(-1), i.v.) pretreatment reduced this
      effect. CONCLUSIONS AND IMPLICATIONS: These results suggest that H2S and NO react
      together to form a molecule (possibly a nitrosothiol) which exhibits little or no
      vasorelaxant activity either in vitro or in vivo. We propose that a crucial, and
      hitherto unappreciated, role of H2S in the vascular system is the regulation of
      the availability of NO.

PMID- 17016508
TI  - Pharmacological and molecular evidence for the involvement of Kv4.3 in ultra-fast
      activating K+ currents in murine portal vein myocytes.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the molecular
      identity of a transient K+ current (termed IUF) in mouse portal vein myocytes
      using pharmacological and molecular tools. EXPERIMENTAL APPROACH: Whole cell
      currents were recorded using the ruptured patch con from either acutely dispersed
      single smooth muscle cells from the murine portal vein or human embryonic kidney
      cells. Reverse transcriptase polymerase reaction (RT-PCR) experiments were
      undertaken on RNA isolated from mouse portal vein using primers specific for
      various voltage-dependent K+ channels, auxillary subunits and calcium-binding
      proteins. Immunocytochemistry was undertaken using an antibody specific for
      Kv4.3. KEY RESULTS: IUF had a mean amplitude at +40 mV of 558 +/- 50 pA (n = 32)
      with a mean time to peak at +40 mV of approximately 4 ms. IUF activated and
      inactivated with a half maximal voltage of -12 +/- 2 mV and -85 +/- 2 mV,
      respectively. IUF was relatively resistant to 4-aminopyridine (5 mM produced 30
      +/- 6 % block at +20 mV) but was inhibited effectively by flecainide (IC50 value
      was 100 nM) and phrixotoxin II. This pharmacological profile is consistent with
      IUF being comprised of Kv4.x proteins and this is supported by the results from
      the quantitative PCR and immunocytochemical experiments. CONCLUSIONS AND
      IMPLICATIONS: These data represent a rigorous investigation of the molecular
      basis of vascular transient K+ currents and implicates Kv4.3 as a major component
      of the channel complex.

PMID- 17016510
TI  - Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via
      activation of TEA-sensitive potassium channels.
AB  - BACKGROUND AND PURPOSE: Central anti-nociceptive actions of baclofen involve
      activation of K+ channels. Here we assessed what types of K+ channel might
      participate in the peripheral anti-nociception induced by baclofen. EXPERIMENTAL
      APPROACH: Nociceptive thresholds to mechanical stimulation in rat paws treated
      with intraplantar prostaglandin E2.(PGE2) to induce hyperalgesia were measured 3
      h after PGE2 injection. Other agents were also given by intraplantar injection.
      KEY RESULTS: Baclofen elicited a dose-dependent (15 - 240 microg per paw) anti
      nociceptive effect. An intermediate dose of baclofen (60 microg) did not produce
      antinociception in the contralateral paw, showing its peripheral site of action.
      The GABAB receptor antagonist saclofen (12.5 - 100 microg per paw) antagonized,
      in a dose-dependent manner, peripheral antinociception induced by baclofen (60
      microg), suggesting a specific effect. This antinociceptive action of baclofen
      was unaffected by bicuculline, GABAA receptor antagonist (80 microg per paw), or
      by (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid, GABAC receptor
      antagonist (20 microg per paw). The peripheral antinociception induced by
      baclofen (60 microg) was reversed, in a dose-dependent manner, by the voltage
      dependent K+ channel blockers tetraethylammonium (7.5 - 30 microg per paw) and 4
      aminopyridine (2.5 - 10 microg per paw). The blockers of other K+ channels,
      glibenclamide (160 microg), tolbutamide (320 microg), charybdotoxin (2 microg),
      dequalinium (50 microg) and caesium (500 microg) had no effect. CONCLUSIONS AND
      IMPLICATIONS: This study provides evidence that the peripheral antinociceptive
      effect of the GABAB receptor agonist baclofen results from the activation of
      tetraethylammonium-sensitive K+ channels. Other K+ channels appear not to be
      involved.

PMID- 17016509
TI  - Inhibition of glycogen synthase kinase-3beta attenuates the development of
      carrageenan-induced lung injury in mice.
AB  - BACKGROUND AND PURPOSE: Glycogen synthase kinase-3 (GSK-3) is a ubiquitous serine
      threonine protein kinase that participates in a multitude of cellular processes
      and has recently been implicated in the pathophysiology of a number of diseases.
      The aim of this study was to investigate the effects of GSK-3beta inhibition in a
      model of acute inflammation. Here, we have investigated the effects of TDZD-8, a
      potent and selective GSK-3beta inhibitor, in a mouse model of carrageenan-induced
      pleurisy. EXPERIMENTAL APPROACH: Injection of carrageenan into the pleural cavity
      of mice elicited an acute inflammatory response characterized by: accumulation of
      fluid containing a large number of neutrophils (PMNs) in the pleural cavity,
      infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and
      increased production of nitrite/nitrate (NOx), prostaglandin E2 (PGE2), tumour
      necrosis factor-alpha, (TNF-alpha) and interleukin-1beta (IL-1beta). Furthermore,
      carrageenan induced an upregulation of the adhesion molecules ICAM-1 and P
      selectin, iNOS, COX-2 as well as nitrotyrosine as determined by
      immunohistochemical analysis of lung tissues. KEY RESULTS: Administration of TDZD
      8 (1, 3 or 10 mg kg(-1), i.p.), 30 min prior to injection of carrageenan, caused
      a dose-dependent reduction in all the parameters of inflammation measured.
      CONCLUSIONS AND IMPLICATIONS: Thus, based on these findings we propose that
      inhibitors of the activity of GSK-3beta, such as TDZD-8, may be useful in the
      treatment of various inflammatory diseases.

PMID- 17016511
TI  - Inhibition of cardiac voltage-gated sodium channels by grape polyphenols.
AB  - BACKGROUND AND PURPOSE: The cardiovascular benefits of red wine consumption are
      often attributed to the antioxidant effects of its polyphenolic constituents,
      including quercetin, catechin and resveratrol. Inhibition of cardiac voltage
      gated sodium channels (VGSCs) is antiarrhythmic and cardioprotective. As
      polyphenols may also modulate ion channels, and possess structural similarities
      to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition
      may contribute to cardioprotection by these polyphenols. EXPERIMENTAL APPROACH:
      The whole-cell voltage-clamp technique was used to record peak and late VGSC
      currents (INa) from recombinant human heart NaV1.5 channels expressed in tsA201
      cells. Right ventricular myocytes from rat heart were isolated and single
      myocytes were field-stimulated. Either calcium transients or contractility were
      measured using the calcium-sensitive dye Calcium-Green 1AM or video edge
      detection, respectively. KEY RESULTS: The red grape polyphenols quercetin,
      catechin and resveratrol blocked peak INa with IC50s of 19.4 microM, 76.8 microM
      and 77.3 microM, respectively. In contrast to lidocaine, resveratrol did not
      exhibit any frequency-dependence of peak INa block. Late INa induced by the VGSC
      long QT mutant R1623Q was reduced by resveratrol and quercetin. Resveratrol and
      quercetin also blocked late INa induced by the toxin, ATX II, with IC50s of 26.1
      microM and 24.9 microM, respectively. In field-stimulated myocytes, ATXII-induced
      increases in diastolic calcium were prevented and reversed by resveratrol. ATXII
      induced contractile dysfunction was delayed and reduced by resveratrol.
      CONCLUSIONS AND IMPLICATIONS: Our results indicate that several red grape
      polyphenols inhibit cardiac VGSCs and that this effect may contribute to the
      documented cardioprotective efficacy of red grape products.

PMID- 17016512
TI  - Beta3-adrenoceptor agonist stimulation of the Na+, K+ -pump in rat skeletal
      muscle is mediated by beta2- rather than beta3-adrenoceptors.
AB  - BACKGROUND AND PURPOSE: In cardiac muscle, BRL 37344, a selective beta3
      adrenoceptor agonist, activates the Na+, K+ -pump via NO signalling. This study
      investigated whether BRL 37344 also activates the Na+, K+ -pump via beta3
      adrenoceptors in skeletal muscle. EXPERIMENTAL APPROACH: Isolated rat soleus
      muscles were incubated between 1 and 60 min in buffer. Intracellular Na+, K+
      content and Na+, K+ -pump activity were measured using flame photometry and
      ouabain-suppressible 86Rb+ uptake, respectively. Additional muscles were mounted
      on force transducers and stimulated (60 Hz for 2 s) every 10 min. KEY RESULTS:
      BRL 37344 (10(-8) -10(-5) M) induced a concentration- and time-dependent
      reduction in intracellular Na+, and increased ouabain-suppressible 86Rb+ uptake
      by up to 112%. BRL 37344-induced reductions in intracellular Na+ were blocked by
      the beta1/beta2-adrenoceptor antagonist, nadolol (10(-7) M), and the beta2
      adrenoceptor antagonist, ICI 118,551 (10(-7) -10(-5) M), but not by beta3- or
      beta1-adrenoceptor antagonists, SR 59230A (10(-7) M) and CGP 20712A (10(-7) -10(
      5) M), respectively. Another beta3-adrenoceptor agonist, CL 316,243, did not
      alter intracellular Na+. BRL 37344-induced reductions in intracellular Na+ were
      not blocked by L-NAME, an NOS inhibitor, or ODQ, a guanylyl cyclase inhibitor.
      The NO donors, SNP and SNAP, did not alter intracellular Na+. BRL 37344 rapidly
      recovered force in muscles depressed by high [K+]o, an effect that was blocked by
      nadolol, but not L-NAME. CONCLUSIONS AND IMPLICATIONS: In rat soleus muscle, the
      beta3-adrenoceptor agonist BRL 37344 stimulated the Na+, K+ -pump via beta2
      adrenoceptors. A more selective beta3-adrenoceptor agonist did not affect Na+, K+
      homeostasis in skeletal muscle. NO did not seem to mediate Na+, K+ -pump
      stimulation in skeletal muscle.

PMID- 17016513
TI  - Actions of ZD0947, a novel ATP-sensitive K+ channel opener, on membrane currents
      in human detrusor myocytes.
AB  - BACKGROUND AND PURPOSE: ATP-sensitive K+ channels (K(ATP) channels) play
      important roles in regulating the resting membrane potential of detrusor smooth
      muscle. Actions of ZD0947, a novel KATP channel opener, on both carbachol (CCh)
      induced detrusor contractions and membrane currents in human urinary bladder
      myocytes were investigated. EXPERIMENTAL APPROACH: Tension measurements and patch
      clamp techniques were utilized to study the effects of ZD0947 in segments of
      human urinary bladder. Immunohistochemistry was also performed to detect the
      expression of the sulphonylurea receptor 1 (SUR1) and the SUR2B antigens in human
      detrusor muscle. KEY RESULTS: ZD0947 (> or = 0.1 microM) caused a concentration
      dependent relaxation of the CCh-induced contraction of human detrusor, which was
      reversed by glibenclamide. The rank order of the potency to relax the CCh-induced
      contraction was pinacidil > ZD0947 > diazoxide. In conventional whole-cell
      configuration, ZD0947 (> or = 1 microM) caused a concentration-dependent inward
      K+ current which was suppressed by glibenclamide at -60 mV. When 1 mM ATP was
      included in the pipette solution, application of pinacidil or ZD0947 caused no
      inward K+ current at -60 mV. Gliclazide (< or =1 microM), a selective SUR1
      blocker, inhibited the ZD0947-induced currents (Ki = 4.0 microM) and the
      diazoxide-induced currents (high-affinity site, Ki1 = 42.4 nM; low-affinity site,
      Ki2 = 84.5 microM) at -60 mV. Immunohistochemical studies indicated the presence
      of SUR1 and SUR2B proteins, which are constituents of KATP channels, in the
      bundles of human detrusor smooth muscle. CONCLUSIONS AND IMPLICATIONS: These
      results suggest that ZD0947 caused a glibenclamide-sensitive detrusor relaxation
      through activation of glibenclamide-sensitive KATP channels in human urinary
      bladder.

PMID- 17016514
TI  - Antidystonic effects of Kv7 (KCNQ) channel openers in the dt sz mutant, an animal
      model of primary paroxysmal dystonia.
AB  - BACKGROUND AND PURPOSE: Mutations in neuronal Kv7 (KCNQ) potassium channels can
      cause episodic neurological disorders. Paroxysmal dyskinesias with dystonia are a
      group of movement disorders which are regarded as ion channelopathies, but the
      role of Kv7 channels in the pathogenesis and as targets for the treatment have so
      far not been examined. EXPERIMENTAL APPROACH: In the present study, we therefore
      examined the effects of the activators of neuronal Kv7.2/7.3 channels retigabine
      (5, 7.5, 10 mg kg(-1) i.p. and 10, 20 mg kg(-1) p.o.) and flupirtine (10, 20 mg
      kg(-1) i.p.) and of the channel blocker 10,10-bis(4-pyridinylmethyl)-9(10H)
      anthracenone (XE-991, 3 and 6 mg kg(-1) i.p.) in the dt sz mutant hamster, a
      model of paroxysmal dyskinesia in which dystonic episodes occur in response to
      stress. KEY RESULTS: Retigabine (10 mg kg(-1) i.p., 20 mg kg(-1) p.o.) and
      flupirtine (20 mg kg(-1) i.p.) significantly improved dystonia, while XE-991
      caused a significant aggravation in the dt sz mutant. The antidystonic effect of
      retigabine (10 mg kg(-1) i.p.) was counteracted by XE-991 (3 mg kg(-1) i.p.).
      CONCLUSIONS AND IMPLICATIONS: These data indicate that dysfunctions of neuronal
      Kv7 channels deserve attention in dyskinesias. Since retigabine and flupirtine
      are well tolerated in humans, the present finding of pronounced antidystonic
      efficacy in the dt sz mutant suggests that neuronal Kv7 channel activators are
      interesting candidates for the treatment of dystonia-associated dyskinesias and
      probably of other types of dystonias. The established analgesic effects of Kv7
      channel openers might contribute to improvement of these disorders which are
      often accompanied by painful muscle spasms.

PMID- 17016515
TI  - Blockade of mGluR1 receptor results in analgesia and disruption of motor and
      cognitive performances: effects of A-841720, a novel non-competitive mGluR1
      receptor antagonist.
AB  - BACKGROUND AND PURPOSE: To further assess the clinical potential of the blockade
      of metabotropic glutamate receptors (mGluR1) for the treatment of pain.
      EXPERIMENTAL APPROACH: We characterized the effects of A-841720, a novel, potent
      and non-competitive mGluR1 antagonist in models of pain and of motor and
      cognitive function. KEY RESULTS: At recombinant human and native rat mGluR1
      receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC50
      values of 10.7+/-3.9 and 1.0 +/- 0.2 nM, respectively, while showing selectivity
      over other mGluR receptors, in addition to other neurotransmitter receptors, ion
      channels, and transporters. Intraperitoneal injection of A-841720 potently
      reduced complete Freund's adjuvant-induced inflammatory pain (ED50 = 23 micromol
      kg(-1)) and monoiodoacetate-induced joint pain (ED50 = 43 micromol kg(-1)). A
      841720 also decreased mechanical allodynia observed in both the sciatic nerve
      chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of
      neuropathic pain (ED50 = 28 and 27 micromol kg(-1), respectively).
      Electrophysiological studies demonstrated that systemic administration of A
      841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic
      range neurons. Significant motor side effects were observed at analgesic doses
      and A-841720 also impaired cognitive function in the Y-maze and the Water Maze
      tests. CONCLUSIONS AND IMPLICATIONS: The analgesic effects of a selective mGluR1
      receptor antagonist are associated with motor and cognitive side effects. The
      lack of separation between efficacy and side effects in pre-clinical models
      indicates that mGluR1 antagonism may not provide an adequate therapeutic window
      for the development of such antagonists as novel analgesic agents in humans.

PMID- 17016516
TI  - Integration of metabolome data with metabolic networks reveals reporter
      reactions.
AB  - Interpreting quantitative metabolome data is a difficult task owing to the high
      connectivity in metabolic networks and inherent interdependency between enzymatic
      regulation, metabolite levels and fluxes. Here we present a hypothesis-driven
      algorithm for the integration of such data with metabolic network topology. The
      algorithm thus enables identification of reporter reactions, which are reactions
      where there are significant coordinated changes in the level of surrounding
      metabolites following environmental/genetic perturbations. Applicability of the
      algorithm is demonstrated by using data from Saccharomyces cerevisiae. The
      algorithm includes preprocessing of a genome-scale yeast model such that the
      fraction of measured metabolites within the model is enhanced, and thus it is
      possible to map significant alterations associated with a perturbation even
      though a small fraction of the complete metabolome is measured. By combining the
      results with transcriptome data, we further show that it is possible to infer
      whether the reactions are hierarchically or metabolically regulated. Hereby, the
      reported approach represents an attempt to map different layers of regulation
      within metabolic networks through combination of metabolome and transcriptome
      data.

PMID- 17016517
TI  - Depicting combinatorial complexity with the molecular interaction map notation.
AB  - To help us understand how bioregulatory networks operate, we need a standard
      notation for diagrams analogous to electronic circuit diagrams. Such diagrams
      must surmount the difficulties posed by complex patterns of protein modifications
      and multiprotein complexes. To meet that challenge, we have designed the
      molecular interaction map (MIM) notation (http://discover.nci.nih.gov/mim/). Here
      we show the advantages of the MIM notation for three important types of diagrams:
      (1) explicit diagrams that define specific pathway models for computer
      simulation; (2) heuristic maps that organize the available information about
      molecular interactions and encompass the possible processes or pathways; and (3)
      diagrams of combinatorially complex models. We focus on signaling from the
      epidermal growth factor receptor family (EGFR, ErbB), a network that reflects the
      major challenges of representing in a compact manner the combinatorial complexity
      of multimolecular complexes. By comparing MIMs with other diagrams of this
      network that have recently been published, we show the utility of the MIM
      notation. These comparisons may help cell and systems biologists adopt a
      graphical language that is unambiguous and generally understood.

PMID- 17016518
TI  - Global systems biology, personalized medicine and molecular epidemiology.

PMID- 17016519
TI  - Global gene expression of Prochlorococcus ecotypes in response to changes in
      nitrogen availability.
AB  - Nitrogen (N) often limits biological productivity in the oceanic gyres where
      Prochlorococcus is the most abundant photosynthetic organism. The Prochlorococcus
      community is composed of strains, such as MED4 and MIT9313, that have different N
      utilization capabilities and that belong to ecotypes with different depth
      distributions. An interstrain comparison of how Prochlorococcus responds to
      changes in ambient nitrogen is thus central to understanding its ecology. We
      quantified changes in MED4 and MIT9313 global mRNA expression, chlorophyll
      fluorescence, and photosystem II photochemical efficiency (Fv/Fm) along a time
      series of increasing N starvation. In addition, the global expression of both
      strains growing in ammonium-replete medium was compared to expression during
      growth on alternative N sources. There were interstrain similarities in N
      regulation such as the activation of a putative NtcA regulon during N stress.
      There were also important differences between the strains such as in the
      expression patterns of carbon metabolism genes, suggesting that the two strains
      integrate N and C metabolism in fundamentally different ways.

PMID- 17016521
TI  - Towards comprehensive characterization of HER2 overexpression.

PMID- 17016522
TI  - The association between HTR2C polymorphisms and obesity in psychiatric patients
      using antipsychotics: a cross-sectional study.
AB  - The use of antipsychotics is associated with an increased risk of obesity. This
      consideration makes it important to search for determinants that can predict the
      risk for antipsychotic-induced obesity. In this cross-sectional study, we
      investigated whether polymorphisms in the HTR2C gene were associated with obesity
      (body mass index >30 kg/m2) in patients using antipsychotics. We examined
      polymorphisms in the promoter region of the HTR2C gene ((HTR2C:c.1-142948(GT)n,
      rs3813928 (-997 G/A), rs3813929 (-759 C/T), rs518147 (-697 G/C)) and an
      intragenic polymorphism (rs1414334:C>G). The results of the logistic regression
      were expressed as adjusted odds ratios (OR). In total, we included 127 patients
      mainly diagnosed with schizophrenia or schizoaffective disorder (89%). The
      results indicate that a combined genotype carrying the variant HTR2C:c.1
      142948(GT)n 13 repeat allele, the common allele rs3813929 C, the variant allele
      rs518147 C and the variant allele rs1414334 C is significantly related to an
      increased risk of obesity (OR 3.71 (95% confidence interval: 1.24-11.12)).

PMID- 17016520
TI  - Effects of HER2 overexpression on cell signaling networks governing proliferation
      and migration.
AB  - Although human epidermal growth factor receptor 2 (HER2) overexpression is
      implicated in tumor progression for a variety of cancer types, how it
      dysregulates signaling networks governing cell behavioral functions is poorly
      understood. To address this problem, we use quantitative mass spectrometry to
      analyze dynamic effects of HER2 overexpression on phosphotyrosine signaling in
      human mammary epithelial cells stimulated by epidermal growth factor (EGF) or
      heregulin (HRG). Data generated from this analysis reveal that EGF stimulation of
      HER2-overexpressing cells activates multiple signaling pathways to stimulate
      migration, whereas HRG stimulation of these cells results in amplification of a
      specific subset of the migration signaling network. Self-organizing map analysis
      of the phosphoproteomic data set permitted elucidation of network modules
      differentially regulated in HER2-overexpressing cells in comparison with parental
      cells for EGF and HRG treatment. Partial least-squares regression analysis of the
      same data set identified quantitative combinations of signals within the networks
      that strongly correlate with cell proliferation and migration measured under the
      same battery of conditions. Combining these modeling approaches enabled
      association of epidermal growth factor receptor family dimerization to activation
      of specific phosphorylation sites, which appear to most critically regulate
      proliferation and/or migration.

PMID- 17016523
TI  - Cataract surgery in Canada.

PMID- 17016524
TI  - Glaucoma in the brain: a piece of the puzzle.

PMID- 17016527
TI  - Canadian Glaucoma Study: 1. Study design, baseline characteristics, and
      preliminary analyses.
AB  - BACKGROUND: The Canadian Glaucoma Study is a multicentered, prospective
      longitudinal study designed to study a variety of systemic risk factors for the
      progression of open-angle glaucoma under a standardised interventional protocol
      for intraocular pressure (IOP) control. METHODS: Newly or previously diagnosed
      patients with early to moderate open-angle glaucoma were recruited consecutively
      from 5 hospital-based university departments. Baseline parameters, including an
      assessment of peripheral vasospasm, haematologic, coagulation, and
      immunopathologic variables were obtained. Newly diagnosed patients were targeted
      for a >or=30% reduction in IOP, whereas previously diagnosed patients entered the
      study at a physician-defined target IOP. After baseline examinations, patients
      were followed at 4-month intervals with standard automated perimetry, short
      wavelength automated perimetry, and confocal scanning laser tomography, and at 28
      32-month intervals with stereo disc photography. If the patient had visual field
      progression with standard automated perimetry, a further >or=20% reduction in IOP
      was mandated. A standardized IOP treatment protocol, ranging from topical
      monotherapy to filtration surgery, was implemented. RESULTS: A total of 258
      patients (131 [corrected] men and 127 [corrected] women, median age 65.0 years)
      were enrolled. Baseline median values for visual acuity, visual field mean
      deviation, untreated IOP, and refractive error were 0.10 logMAR, -4.04 dB, 25.0
      mm Hg, and 0.00 D, respectively. Approximately 30% of the patients were
      hypertensive, 16% had cardiovascular disease, 9% thyroid disease, 9% diabetes,
      14% migraine, and 19% were smokers. The median follow-up was 5.3 years, with 148
      (57.0%) and 51 (19.8%) patients completing >or=5 and >or=7 years follow-up,
      respectively. The cumulative visual field progression rate at 2, 4, 6, and 8
      years was 11.3%, 21.5%, 33.1%, and 43.5%, respectively. INTERPRETATION: We
      describe the study design and baseline patient characteristics of the Canadian
      Glaucoma Study and present some preliminary results. This long and close follow
      up of a large group of patients will reveal the importance of several systemic
      factors for the progression of glaucoma.

PMID- 17016528
TI  - Anterior uveitis investigation by Canadian ophthalmologists: insights from the
      Canadian National Uveitis Survey.
AB  - BACKGROUND: Anterior uveitis can be the result of a number of underlying
      etiologies and is commonly seen in ophthalmology practice. The clinician must
      choose from a battery of potential investigations. A nonselective approach to
      testing is costly and inefficient and can lead to misinterpretation of false
      positive results. The purpose of this study was to identify investigation
      patterns of ophthalmologists in Canada for anterior uveitis and to make evidence
      based recommendations for appropriate tests that could lead to improved patient
      care and more cost-effective use of health care resources. METHODS: A cross
      sectional survey of practicing ophthalmologists, fellows, and residents in Canada
      was conducted in September 2004. The survey instrument was an 11-item
      questionnaire mailed to 1196 physicians in Canada. RESULTS: A total of 498 (42%)
      physicians responded to the survey. A wide range of tests were chosen when
      respondents were presented with 5 scenarios for anterior uveitis and asked what
      investigations they would order. Many of these tests have low diagnostic yields
      because they lack the sensitivity and specificity to be used as routine
      investigations in the setting of anterior uveitis. INTERPRETATION: Increased
      education and awareness could lead to more cost-effective and efficient
      investigations in the setting of anterior uveitis. On the basis of evidence from
      a review of the literature, we make recommendations for investigations that
      should be considered in patients with anterior uveitis.

PMID- 17016529
TI  - Ocular integration in the human visual cortex.
AB  - Human striate cortex contains an orderly map of the contralateral visual field,
      which is distorted to make a disproportionate amount of tissue available for the
      representation of the macula. Engrafted on the retinotopic map is a system of
      alternating inputs known as ocular dominance columns. These columns consist of
      interleaved bands of geniculocortical afferents in layer 4C serving either the
      right eye or the left eye. They can be revealed in humans with a history of prior
      visual loss in one eye by processing striate cortex for cytochrome oxidase at
      autopsy. Because their geniculate input is segregated, cells within ocular
      dominance columns in layer 4C respond to stimulation of one eye only. These
      monocular cells converge onto binocular cells in other layers, integrating
      signals from the two eyes. The columns in humans appear similar to those found in
      many primate species, including the macaque. In the squirrel monkey, however, the
      occurrence of ocular dominance columns is highly variable. Some squirrel monkeys
      lack columns, yet they seem to have no impairment of visual function. In animals
      with weakly expressed columns, one can detect a cortical pattern of metabolic
      activity corresponding to retinal blood vessels. It appears because visual
      deprivation from shadows cast by blood vessels induces remodeling of
      geniculocortical afferents, in a manner akin to the shrinkage of ocular dominance
      columns from congenital cataract. Although the function of ocular dominance
      columns is unknown, their metabolism is altered in strabismus, suggesting a role
      in visual suppression.

PMID- 17016530
TI  - Bilateral acute anterior uveitis as a presenting symptom of Mycoplasma pneumoniae
      infection.
AB  - CASE REPORT: To report a case of severe bilateral anterior uveitis associated
      with Mycoplasma pneumoniae without pulmonary manifestations. COMMENTS: A healthy
      5-year-old girl developed severe bilateral anterior uveitis accompanied by fever,
      arthralgia, gastrointestinal complaints, and lethargy. Results of laboratory
      investigations were normal except for high levels of Mycoplasma pneumoniae
      antibodies. The uveitis subsided with topical application of steroids,
      cycloplegia, and with oral azithromycin. Although Mycoplasma pneumoniae is a rare
      cause of uveitis, it should be considered in patients presenting with uveitis,
      even with no accompanying pulmonary or other typical systemic mycoplasmal
      manifestations.

PMID- 17016531
TI  - Factors influencing career choice in ophthalmology.
AB  - BACKGROUND: To investigate the factors influencing choice of ophthalmology as a
      career in medicine. METHODS: Data were extracted from the 2004 National Physician
      Survey, a questionnaire distributed to all physicians across Canada. Data were
      categorized by medical discipline, and chi2 comparative analyses were done.
      RESULTS: Intellectual stimulation emerged as the most frequently cited factor
      influencing career choice for ophthalmologists and nonophthalmologists alike (81%
      and 79%, respectively). Compared with other physicians, ophthalmologists were
      significantly more likely to cite flexibility (58% vs. 42%, respectively),
      mentorship (42% vs. 31%, respectively), and earning potential (38% vs. 26%,
      respectively) as important factors (p<0.001). INTERPRETATION: Intellectual
      stimulation is the principal reason physicians pursue a career in ophthalmology.
      Ophthalmologists cite flexibility, mentorship, and earning potential as important
      factors more frequently than do physicians of other disciplines.

PMID- 17016532
TI  - Branch retinal vein occlusion associated with vitreoretinal traction.
AB  - CASE REPORT: Branch retinal vein occlusion (BRVO) is believed to arise at
      arteriovenous crossing sites. Surgical dissection of the arteriovenous sheath has
      been proposed as a treatment option, yet induction of a posterior vitreous
      detachment may be as important in obtaining a successful surgical outcome,
      suggesting that vitreoretinal traction may play a role in the development of
      BRVO. A retrospective review of 3 patients presenting with clinical features of
      BRVO and evidence of vitreoretinal traction at the occlusion site was conducted.
      COMMENTS: All patients presented with mild vitreous hemorrhage. Intraretinal
      hemorrhages were distributed in an unusual linear pattern along the involved
      venous segment, suggesting the presence of vitreoretinal traction. Fluorescein
      angiography demonstrated blocked fluorescence secondary to hemorrhage with delay
      of venous flow at the avulsion site. Partial avulsion of the involved venous
      segment was evident on clinical examination, B-scan ultrasound, or optical
      coherence tomography. Vitreoretinal traction may contribute to the pathogenesis
      of BRVO in some patients.

PMID- 17016533
TI  - Photopsia as a manifestation of digitalis toxicity.
AB  - CASE REPORT: To present a case of photopsia resulting from digoxin intoxication
      brought about by dehydration in a 72-year-old woman. COMMENTS: Ophthalmologists
      may be the first clinicians to notice the symptoms of digitalis intoxication,
      which is potentially a life-threatening condition.

PMID- 17016534
TI  - Choroidal mass as the presenting sign of small cell lung carcinoma.
AB  - CASE REPORT: To report the case of a 58-year-old man with blurred vision and
      metamorphopsia who had an amelanotic choroidal mass in the right eye as the
      presenting sign of a small cell lung carcinoma. Systemic screening failed to
      reveal a tumor elsewhere, and the lesion was initially treated as a primary
      ocular tumor. Discovery of the primary site was made 10 months after the ocular
      diagnosis, and the patient was then treated with systemic chemotherapy and local
      radiation therapy. COMMENTS: The ophthalmologist has a crucial role not only in
      the management of ocular metastases but also in the diagnosis of the primary
      nonocular malignancies that present as a choroidal mass. The possibility of
      ocular metastases in patients with choroidal masses should always be considered
      whether or not there is a diagnosis of cancer elsewhere.

PMID- 17016535
TI  - Isolated bilateral lateral geniculate infarction producing bow-tie visual field
      defects.
AB  - CASE REPORT: We examined a unique case of stroke in a 29-year-old woman. Magnetic
      resonance imaging revealed isolated bilateral acute infarctions of the lateral
      geniculate bodies (LGB). Visual field testing demonstrated incongruous but
      homonymous bilateral visual field loss in a bow-tie configuration. COMMENTS:
      Isolated bilateral damage to the LGB is a rare event. Literature review has
      revealed only 4 previous incidents of bilateral damage to both LGB. We present a
      literature review and a case of bilateral LGB infarction producing visual field
      defects suggestive of bilateral lateral choroidal artery involvement in an
      individual with classic migraine.

PMID- 17016536
TI  - Prognostic DNA testing and counselling for dominant optic atrophy due to a novel
      OPA1 mutation.
AB  - CASE REPORT: To report the case of a 26-year-old woman with a family history of
      dominant optic atrophy who requested DNA testing and counselling. Ophthalmologic
      examination showed her affected father had bilateral temporal papillary pallor.
      Direct genomic sequencing of the OPA1 gene revealed a novel heterozygous nonsense
      mutation (Arg879stop). Because no mutation in OPA1 was detected in the daughter,
      we could counsel her that the possibility was very low that she was a carrier or
      would pass the disease-causing gene to her children. COMMENTS: Our study provides
      evidence of the apparent value of molecular genetic analysis of OPA1 gene as
      predictive DNA testing, although the exact risk and benefit of this type of
      analysis awaits further study.

PMID- 17016537
TI  - Awareness of eye diseases and risk factors: identifying needs for health
      education and promotion in Canada.
AB  - BACKGROUND: Little is known about the level of general public knowledge in Canada
      regarding the risk factors, prevention, and treatment of major blinding eye
      diseases. METHODS: The study was a cross-sectional survey using self-administered
      questionnaires of patients presenting to 33 family practitioners' offices in
      British Columbia. We asked patients' opinions on the "value" of preventing
      blindness; the possibility of preventing cataract, glaucoma, and macular
      degeneration; the possibility of treating these conditions; and their knowledge
      of risk factors. RESULTS: A total of 882 adults completed the questionnaires.
      Preventing vision loss was reported as one of 2 top health priorities in 28% of
      the questionnaires, more commonly by those with higher education and non-European
      ancestry. Overall, 69.2% reported familiarity with cataract as a cause of vision
      loss, 41.2% with glaucoma, and 20.2% with macular degeneration. Of these, 97.5%
      recognized the possibility of treatment for cataract, 91.5% for glaucoma, and
      77.0% for macular degeneration, yet few respondents knew risk factors (amenable
      to intervention) for specific eye diseases. Men and younger respondents were more
      likely to report not knowing risk factors. Chinese-Canadians were least familiar
      with the association between smoking and cataract. Family history, probably the
      most important factor to help diagnose glaucoma, was recognized by only 23% of
      respondents. INTERPRETATION: Although loss of vision was reported as a major
      medical concern, there is little understanding of the risk factors for different
      eye diseases. The association of non-European ancestry and low educational
      attainment with poor knowledge of eye diseases suggests that innovative education
      programmes in primary and secondary schools and in non-English languages are
      needed to improve knowledge, attitudes, and practices.

PMID- 17016538
TI  - Effect of diclofenac on prevention of posterior capsule opacification in human
      eyes.
AB  - BACKGROUND: Diclofenac sodium has been demonstrated to be effective in preventing
      proliferation of lens epithelial cells both in vitro and in animal studies. The
      effects of diclofenac sodium given during the hydrodissection stage of
      phacoemulsification surgery on posterior capsule opacification (PCO) were
      investigated. METHODS: Eleven patients undergoing phacoemulsification in both
      eyes were included. Patients with pseudoexfoliation, uveitis, and diabetes were
      excluded. Hydrodissection was done with only balanced salt solution in the first
      eyes. In the fellow eyes, 0.25 mg/mL diclofenac was given with hydrodissection.
      The same type of intraocular lens was implanted in both eyes of each patient.
      Follow-up was 21.8 (SD 3.5) months in the diclofenac group and 22.9 (3.7) months
      in the control group. PCO was evaluated clinically by dividing the posterior
      capsule into 24 zones. Mann-Whitney U test was used for statistical analysis.
      RESULTS: There were no statistically significant differences of age, diameter of
      capsulorhexis, pupillary width, visual acuity, intraocular pressure, or length of
      follow-up between groups. PCO score was 0.49 (SD 0.21) in eyes receiving
      diclofenac and 0.73 (0.23) in the contralateral fellow eyes. The difference was
      not statistically significant (p=0.053). INTERPRETATION: Diclofenac sodium given
      by hydrodissection in phacoemulsification decreased, but did not significantly
      prevent, the development of PCO.

PMID- 17016539
TI  - Primary intraosseous hemangioma of the orbit: an unusual presentation of an
      uncommon tumor.
AB  - CASE REPORT: An asymptomatic patient was referred for assessment of an
      intraocular amelanotic mass in her left eye. Examination showed a mass effect in
      the inferior location at the 5 o'clock position. This abnormality was defined
      with ultrasound biomicroscopy and standard ultrasound, but because the appearance
      was not typical of a melanoma or other choroidal infiltrate, magnetic resonance
      images and computed tomograms of the orbits were obtained, identifying an
      extraocular mass arising from the zygomatic rim. Results of a biopsy reported an
      intraosseous hemangioma. COMMENTS: The diagnosis of intraosseous hemangioma,
      because of its low incidence and unusual manner of presentation, can be
      challenging. Computed tomography and biopsy are helpful in making a definitive
      diagnosis.

PMID- 17016540
TI  - Moyamoya disease presenting to the ophthalmology clinic.

PMID- 17016542
TI  - Three steps to protecting pediatric research participants from excessive risks.

PMID- 17016543
TI  - Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone
      trials: secondary analysis of a randomized trial.
AB  - OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use
      might have counteracted a beneficial effect of postmenopausal hormone therapy,
      and account for the absence of cardioprotection in the Women's Health Initiative
      hormone trials. Estrogen increases COX expression, and inhibitors of COX such as
      nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising
      the possibility of a clinically important interaction in the trials. DESIGN: The
      hormone trials were randomized, double-blind, and placebo-controlled. Use of
      nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3,
      and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40
      clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347
      postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women
      with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone
      acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to
      conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial
      infarction, coronary death, and coronary revascularization were ascertained
      during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of
      follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence
      intervals were calculated from Cox proportional hazard models stratified by COX
      inhibitor use. The hazard ratio for myocardial infarction/coronary death with
      estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non
      users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among
      continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence
      interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence
      interval 0.69-1.70) among continuous users. In a second analytic approach, hazard
      ratios were calculated from Cox models that included hormone trial assignment as
      well as a time-dependent covariate for medication use, and an interaction term.
      No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did
      not significantly affect the Women's Health Initiative hormone trial results.

PMID- 17016544
TI  - Stereotype Directionality and Attractiveness Stereotyping: Is Beauty Good or is
      Ugly Bad?
AB  - Dion, Berscheid, and Walster (1972), in their seminal article, labeled the
      attribution of positive characteristics to attractive people the "beauty-is-good"
      stereotype. The stereotyping literature since then provides extensive evidence
      for the differential judgment and treatment of attractive versus unattractive
      people, but does not indicate whether it is an advantage to be attractive or a
      disadvantage to be unattractive. Two studies investigated the direction of
      attractiveness stereotyping by comparing judgments of positive and negative
      attributes for medium vs. low and medium vs. high attractive faces. Taken
      together, results for adults (Experiment 1) and children (Experiment 2) suggest
      that most often, unattractiveness is a disadvantage, consistent with negativity
      bias (e.g., Rozin & Royzman, 2001) but contrary to the "beauty-is-good" aphorism.

PMID- 17016545
TI  - When Goals Conflict But People Prosper: The Case of Dispositional Optimism.
AB  - Optimistic persistence in pursuing goals may have beneficial consequences such as
      protection against negative affect and greater likelihood of goal attainment, but
      persistence can also result in greater likelihood of goal conflict, which can
      have negative consequences. Two studies, one cross-sectional (N = 100) and one
      longitudinal (N = 77), found that optimism associated with higher goal conflict.
      However, objectively rated goal conflict did not significantly undermine
      adjustment, and when balance among goal value, expectancy, and conflict was
      considered, optimism associated with better balance. In turn, balance accounted
      for part of optimists' better goal progress over the course of a semester.
      Although goal conflict may have costs, these costs appear to be offset by
      accompanying benefits, particularly for optimists.

PMID- 17016546
TI  - Measuring ligand-dependent and ligand-independent interactions between nuclear
      receptors and associated proteins using Bioluminescence Resonance Energy Transfer
      (BRET).
AB  - Bioluminescent resonance energy transfer (BRET2) is a recently developed
      technology for the measurement of protein-protein interactions in a live, cell
      based system. BRET2 is characterized by the efficient transfer of excited energy
      between a bioluminescent donor molecule (Renilla luciferase) and a fluorescent
      acceptor molecule (a mutant of Green Fluorescent Protein (GFP2). The BRET2 assay
      offers advantages over fluorescence resonance energy transfer (FRET) because it
      does not require an external light source thereby eliminating problems of
      photobleaching and autoflourescence. The absence of contamination by light
      results in low background that permits detection of very small changes in the
      BRET2 signal. BRET2 is dependent on the orientation and distance between two
      fusion proteins and therefore requires extensive preliminary standardization
      experiments to conclude a positive BRET2 signal independent of variations in
      protein titrations and arrangement in tertiary structures. Estrogen receptor (ER)
      signaling is modulated by steroid receptor coactivator 1 (SRC-1). To establish
      BRET2 in a ligand inducible system we used SRC-1 as the donor moiety and ER as
      the acceptor moiety. Expression and functionality of the fusion proteins were
      assessed by transient transfection in HEK-293 cells followed by Western blot
      analysis and measurement of ER-dependent reporter gene activity. These
      preliminary determinations are required prior to measuring nuclear receptor
      protein-protein interactions by BRET2. This article describes in detail the BRET2
      methodology for measuring interaction between full-length ER and coregulator
      proteins in real-time, in an in vivo environment.

PMID- 17016547
TI  - Effect of physical inactivity on the oxidation of saturated and monounsaturated
      dietary Fatty acids: results of a randomized trial.
AB  - OBJECTIVES: Changes in the way dietary fat is metabolized can be considered
      causative in obesity. The role of sedentary behavior in this defect has not been
      determined. We hypothesized that physical inactivity partitions dietary fats
      toward storage and that a resistance exercise training program mitigates storage.
      DESIGN: We used bed rest, with randomization to resistance training, as a model
      of physical inactivity. SETTING: The trial took place at the Space Clinic
      (Toulouse, France). PARTICIPANTS: A total of 18 healthy male volunteers, of mean
      age +/- standard deviation 32.6 +/- 4.0 y and body mass index 23.6 +/- 0.7
      kg/m(2), were enrolled. INTERVENTIONS: An initial 15 d of baseline data
      collection were followed by 3 mo of strict bed-rest alone (control group, n = 9)
      or with the addition of supine resistance exercise training every 3 d (exercise
      group, n = 9). OUTCOME MEASURES: Oxidation of labeled [d(31)]palmitate (the main
      saturated fatty acid of human diet) and [1-(13)C]oleate (the main monounsaturated
      fatty acid), body composition, net substrate use, and plasma hormones and
      metabolites were measured. RESULTS: Between-group comparisons showed that
      exercise training did not affect oxidation of both oleate (mean difference 5.6%;
      95% confidence interval [95% CI], -3.3% to 14.5%; p = 0.20) and palmitate (mean
      difference -0.2%; 95% CI, -4.1% to 3.6%; p = 0.89). Within-group comparisons,
      however, showed that inactivity changed oxidation of palmitate in the control
      group by -11.0% (95% CI, -19.0% to -2.9%; p = 0.01) and in the exercise group by 
      11.3% (95% CI, -18.4% to -4.2%; p = 0.008). In contrast, bed rest did not
      significantly affect oleate oxidation within groups. In the control group, the
      mean difference in oleate oxidation was 3.2% (95% CI, -4.2% to 10.5%; p = 0.34)
      and 6.8% (95% CI, -1.2% to 14.7%; p = 0.08) in the exercise group. CONCLUSIONS:
      Independent of changes in energy balance (intake and/or output), physical
      inactivity decreased the oxidation of saturated but not monounsaturated dietary
      fat. The effect is apparently not compensated by resistance exercise training.
      These results suggest that Mediterranean diets should be recommended in sedentary
      subjects and recumbent patients.

PMID- 17016548
TI  - Response to Zhou et al. Osteomalacia is a frequent complication resulting from
      long-term therapy with drugs such as phenytoin, carbamazepine, and phenobarbital.

PMID- 17016549
TI  - The physician-scientist, the state, and the oath: thoughts for our times.
AB  - Triggered by an encounter with survivors of the studies on twins conducted in
      Auschwitz by Joseph Mengele, who held both MD and PhD degrees, I offer thoughts
      on the extraordinary powers physician-scientists have to enhance or degrade human
      dignity. Biomedical science lacks intrinsic morality, but attains moral status by
      virtue of its purpose and the ethical framework that controls its conduct, both
      of which derive from the principles of medical humanism codified in the
      physician's oath. Physician-scientists have responsibilities to humankind that
      transcend the state. Careful analysis of historical examples of abuses of human
      rights committed in the name of medical science or the state is an important
      mechanism to safeguard current and future human participants.

PMID- 17016551
TI  - T cell activation alters intestinal structure and function.
AB  - Treatment with anti-CD3 antibody (anti-CD3) causes transient diarrhea. In this
      issue of the JCI, Clayburgh et al. show that, in jejunum of mice injected with
      anti-CD3 or with TNF, fluid accumulation and changes in epithelial phenotype
      develop, the latter including an increase in the passive permeability to
      proteins, smaller solutes, and water and the endocytosis of the brush border
      Na+/H+ exchanger, thereby inhibiting Na+ absorption (a second cytokine, LIGHT,
      has the former effect, but not the latter) (see the related article beginning on
      page 2682). These phenotypic changes, by themselves, do not, however, explain
      increased fluid secretion. Since active anion secretion is not stimulated (in
      fact it is inhibited), a non-epithelial cell-mediated driving force must be
      present--most likely an increase in interstitial pressure due to an effect of TNF
      on capillary permeability, smooth muscle contractility, or both.

PMID- 17016550
TI  - Deiodinases: implications of the local control of thyroid hormone action.
AB  - The deiodinases activate or inactivate thyroid hormone, and their importance in
      thyroid hormone homeostasis has become increasingly clear with the availability
      of deiodinase-deficient animals. At the same time, heightened interest in the
      field has been generated following the discovery that the type 2 deiodinase can
      be an important component in both the Hedgehog signaling pathway and the G
      protein-coupled bile acid receptor 1-mediated (GPBAR1-mediated) signaling
      cascade. The discovery of these new roles for the deiodinases indicates that
      tissue-specific deiodination plays a much broader role than once thought,
      extending into the realms of developmental biology and metabolism.

PMID- 17016552
TI  - Pili prove pertinent to enterococcal endocarditis.
AB  - Enterococcus faecalis is an important agent of endocarditis and urinary tract
      infections, which occur frequently in hospitals. Antimicrobial therapy is
      complicated by the emergence of drug-resistant strains, which contribute
      significantly to mortality associated with E. faecalis infection. In this issue
      of the JCI, Nallapareddy and colleagues report that E. faecalis produces pili on
      its surface and that these proteinaceous fibers are used for bacterial adherence
      to host tissues and for the establishment of biofilms and endocarditis (see the
      related article beginning on page 2799). This information may enable new vaccine
      strategies for the prevention of E. faecalis infections.

PMID- 17016553
TI  - Imaging tumor angiogenesis.
AB  - Since the discovery of vascular-specific growth factors with angiogenic activity,
      there has been a significant effort to develop cancer drugs that restrict
      tumorigenesis by targeting the blood supply. In this issue of the JCI, Mancuso et
      al. use mouse models to better understand the plasticity of the tumor vasculature
      in the face of antiangiogenic therapy (see the related article beginning on page
      2610). They describe a rapid regrowth of the tumor vasculature following
      withdrawal of VEGFR inhibitors, emphasizing the importance of fully understanding
      the function of these and similar treatments used in the clinic at the cellular
      and molecular level.

PMID- 17016554
TI  - Myeloid suppressor cells regulate the adaptive immune response to cancer.
AB  - Inflammation resultant from tumor growth, infection with certain pathogens, or in
      some cases, trauma, can result in systemic release of cytokines, especially GM
      CSF, that in turn stimulate the abundant production and activation of a
      population of immature myeloid cells, termed myeloid suppressor cells (MSCs),
      that have potent immunosuppressive functions. In this issue of the JCI, Gallina
      and colleagues have illuminated some complex issues concerning the development,
      activation, and function of MSCs (see the related article beginning on page
      2777). They show that activation of MSCs is initiated in response to IFN-gamma,
      presumably produced in situ by antitumor T cells in the tumor microenvironment.
      After this triggering event, MSCs express 2 enzymes involved in l-arginine
      metabolism, Arginase I and iNOS, whose metabolic products include diffusible and
      highly reactive peroxynitrites, the ultimate biochemical mediators of T cell
      immune suppression. The multifaceted regulation of this complex suppressive
      effector system provides several potential therapeutic targets.

PMID- 17016555
TI  - To be or not to be B7.
AB  - The activation of lymphocytes and development of adaptive immune responses is
      initiated by the engagement of TCRs by antigenic peptide-MHC complexes and shaped
      at the clonal level by both positive and negative costimulatory signals. The B7
      family members are involved at several stages in this process. In this issue of
      the JCI, Vogt et al. show that the B7 family-related protein V-set and Ig domain
      containing 4 (VSIG4) can act as an inhibitor of T cell activation (see the
      related article beginning on page 2817). Intriguingly, the same molecule was
      recently independently identified as a complement receptor of the Ig superfamily
      (CRIg) and was convincingly demonstrated to be a receptor for complement
      component 3 fragments. These findings raise interesting questions regarding the
      physiological roles and mechanisms of action of this molecule. Identification of
      dual functions of this molecule provides an additional level of complexity in T
      cell costimulation.

PMID- 17016556
TI  - Children are not little adults: just ask their hematopoietic stem cells.
AB  - HSCs differ during ontogeny in some important parameters, including anatomic site
      of residence and cell cycling characteristics. In this issue of the JCI, Bowie et
      al. show that postnatal HSCs as well as fetal liver HSCs in mice are active in
      the cell cycle at much higher rates than that of adult HSCs; however, this
      increased frequency of cycling abruptly ceases 4 weeks after birth (see the
      related article beginning on page 2808). The cycling postnatal HSCs expressed
      high levels of CXC chemokine ligand 12 (CXCL12, also known as stromal cell
      derived factor 1 [SDF-1]), a chemokine previously implicated in stem cell
      trafficking to the marrow cavity and shown to be expressed by cells within the
      hematopoietic microenvironment. These cells also possessed an engraftment defect
      impeding reconstitution in irradiated recipient mice, which was reversible by
      pretransplant administration of antagonists of the CXCL12 receptor, CXCR4. Such
      agents are currently clinically available, suggesting that this approach could be
      used to improve stem cell transplantation and engraftment.

PMID- 17016557
TI  - Rapid vascular regrowth in tumors after reversal of VEGF inhibition.
AB  - Inhibitors of VEGF signaling can block angiogenesis and reduce tumor vascularity,
      but little is known about the reversibility of these changes after treatment
      ends. In the present study, regrowth of blood vessels in spontaneous RIP-Tag2
      tumors and implanted Lewis lung carcinomas in mice was assessed after inhibition
      of VEGF receptor signaling by AG-013736 or AG-028262 for 7 days. Both agents
      caused loss of 50%-60% of tumor vasculature. Empty sleeves of basement membrane
      were left behind. Pericytes also survived but had less alpha-SMA
      immunoreactivity. One day after drug withdrawal, endothelial sprouts grew into
      empty sleeves of basement membrane. Vessel patency and connection to the
      bloodstream followed close behind. By 7 days, tumors were fully revascularized,
      and the pericyte phenotype returned to baseline. Importantly, the regrown
      vasculature regressed as much during a second treatment as it did in the first.
      Inhibition of MMPs or targeting of type IV collagen cryptic sites by antibody
      HUIV26 did not eliminate the sleeves or slow revascularization. These results
      suggest that empty sleeves of basement membrane and accompanying pericytes
      provide a scaffold for rapid revascularization of tumors after removal of anti
      VEGF therapy and highlight their importance as potential targets in cancer
      therapy.

PMID- 17016558
TI  - Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for
      TNF-mediated diarrhea in vivo.
AB  - Acute T cell-mediated diarrhea is associated with increased mucosal expression of
      proinflammatory cytokines, including the TNF superfamily members TNF and LIGHT.
      While we have previously shown that epithelial barrier dysfunction induced by
      myosin light chain kinase (MLCK) is required for the development of diarrhea,
      MLCK inhibition does not completely restore water absorption. In contrast,
      although TNF-neutralizing antibodies completely restore water absorption after
      systemic T cell activation, barrier function is only partially corrected. This
      suggests that, while barrier dysfunction is critical, other processes must be
      involved in T cell-mediated diarrhea. To define these processes in vivo, we asked
      whether individual cytokines might regulate different events in T cell-mediated
      diarrhea. Both TNF and LIGHT caused MLCK-dependent barrier dysfunction. However,
      while TNF caused diarrhea, LIGHT enhanced intestinal water absorption. Moreover,
      TNF, but not LIGHT, inhibited Na+ absorption due to TNF-induced internalization
      of the brush border Na+/H+ exchanger NHE3. LIGHT did not cause NHE3
      internalization. PKCalpha activation by TNF was responsible for NHE3
      internalization, and pharmacological or genetic PKCalpha inhibition prevented
      NHE3 internalization, Na+ malabsorption, and diarrhea despite continued barrier
      dysfunction. These data demonstrate the necessity of coordinated Na+
      malabsorption and barrier dysfunction in TNF-induced diarrhea and provide insight
      into mechanisms of intestinal water transport.

PMID- 17016559
TI  - Tumors induce a subset of inflammatory monocytes with immunosuppressive activity
      on CD8+ T cells.
AB  - Active suppression of tumor-specific T lymphocytes can limit the efficacy of
      immune surveillance and immunotherapy. While tumor-recruited CD11b+ myeloid cells
      are known mediators of tumor-associated immune dysfunction, the true nature of
      these suppressive cells and the fine biochemical pathways governing their
      immunosuppressive activity remain elusive. Here we describe a population of
      circulating CD11b+IL-4 receptor alpha+ (CD11b+IL-4Ralpha+), inflammatory-type
      monocytes that is elicited by growing tumors and activated by IFN-gamma released
      from T lymphocytes. CD11b+IL-4Ralpha+ cells produced IL-13 and IFN-gamma and
      integrated the downstream signals of these cytokines to trigger the molecular
      pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous
      immunosuppressive circuits were active in CD11b+ cells present within the tumor
      microenvironment. These suppressor cells challenge the current idea that tumor
      conditioned immunosuppressive monocytes/macrophages are alternatively activated.
      Moreover, our data show how the inflammatory response elicited by tumors had
      detrimental effects on the adaptive immune system and suggest novel approaches
      for the treatment of tumor-induced immune dysfunctions.

PMID- 17016560
TI  - Endocarditis and biofilm-associated pili of Enterococcus faecalis.
AB  - Increasing multidrug resistance in Enterococcus faecalis, a nosocomial
      opportunist and common cause of bacterial endocarditis, emphasizes the need for
      alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In
      an earlier study, we demonstrated the presence of antibodies in E. faecalis
      endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall
      anchored proteins; of these, we have now characterized an in vivo-expressed locus
      of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using
      mutation analyses and complementation, we demonstrated that both the ebp
      (encoding endocarditis and biofilm-associated pili) operon and srtC are important
      for biofilm production of E. faecalis strain OG1RF. In addition, immunogold
      electron microscopy using antisera against EbpA-EbpC proteins as well as patient
      serum demonstrated that E. faecalis produces pleomorphic surface pili. Assembly
      of pili and their cell wall attachment appeared to occur via a mechanism of cross
      linking of the Ebp proteins by the designated SrtC. Importantly, a nonpiliated,
      allelic replacement mutant was significantly attenuated in an endocarditis model.
      These biologically important surface pili, which are antigenic in humans during
      endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful
      immunotarget for studies aimed at prevention and/or treatment of this pathogen.

PMID- 17016563
TI  - Structure and O2-reactivity of copper(I) complexes supported by pyridylalkylamine
      ligands.
AB  - The structure and O2-reactivity of a series of copper(I) complexes supported by
      the pyridylalkylamine ligands are summarized, and the ligand effects such as the
      chelate ring size effect (five- vs. six-membered ring), the denticity effect
      (tetradentate vs. tridentate vs. didentate), the steric effect of 6
      methylpyridine and the steric and/or electronic effects of N-alkyl substituents
      are discussed in detail.

PMID- 17016561
TI  - Hematopoietic stem cells proliferate until after birth and show a reversible
      phase-specific engraftment defect.
AB  - The regulation of HSC proliferation and engraftment of the BM is an important but
      poorly understood process, particularly during ontogeny. Here we show that in
      mice, all HSCs are cycling until 3 weeks after birth. Then, within 1 week, most
      became quiescent. Prior to 4 weeks of age, the proliferating HSCs with long-term
      multilineage repopulating activity displayed an engraftment defect when
      transiting S/G2/M. During these cell cycle phases, their expression of CXC
      chemokine ligand 12 (CXCL12; also referred to as stromal cell-derived factor 1
      [SDF-1]) transiently increased. The defective engrafting activity of HSCs in
      S/G2/M was reversed when cells were allowed to progress into G1 prior to
      injection or when the hosts (but not the cells) were pretreated with a CXCL12
      antagonist. Interestingly, the enhancing effect of CXCL12 antagonist pretreatment
      was exclusive to transplants of long-term multilineage repopulating HSCs in
      S/G2/M. These results demonstrate what we believe to be a new HSC regulatory
      checkpoint during development. They also suggest an ability of HSCs to express
      CXCL12 in a fashion that changes with cell cycle progression and is associated
      with a defective engraftment that can be overcome by in vivo administration of a
      CXCL12 antagonist.

PMID- 17016564
TI  - Distinct methylalumoxane(MAO)-derived Me-MAO- anions in contact with a
      zirconocenium cation--a 13C-NMR study.
AB  - Zirconocenium cations of the type [(MeC5H4)2ZrMe]+, formed by excess
      methylalumoxane (MAO) from (MeC5H4)2ZrCl2 or (MeC5H4)2ZrMe2 with 13C-labelled
      ring ligands, are found to form ion pairs with two types of anions, Me-MAO(A)-
      and Me-MAO(B)-, which differ in their coordinative strengths: More strongly
      coherent ion pairs [(MeC5H4)2ZrMe+...Me-MAO(B)-] are converted to more easily
      separable ion pairs [(MeC5H4)2ZrMe+...Me-MAO(A)-] by a sufficient excess of MAO.
      These react with Al2Me6 to form outer-sphere ion pairs containing the cationic
      AlMe3 adduct [(MeC5H4)2Zr(mu-Me)2AlMe2]+; formation of the more easily separable
      ion pairs might be required also for polymerisation catalysis.

PMID- 17016562
TI  - VSIG4, a B7 family-related protein, is a negative regulator of T cell activation.
AB  - T cell activation by APCs is positively and negatively regulated by members of
      the B7 family. We have identified a previously unknown function for B7 family
      related protein V-set and Ig domain-containing 4 (VSIG4). In vitro experiments
      using VSIG4-Ig fusion molecules showed that VSIG4 is a strong negative regulator
      of murine and human T cell proliferation and IL-2 production. Administration to
      mice of soluble VSIG4-Ig fusion molecules reduced the induction of T cell
      responses in vivo and inhibited the production of Th cell-dependent IgG
      responses. Unlike that of B7 family members, surface expression of VSIG4 was
      restricted to resting tissue macrophages and absent upon activation by LPS or in
      autoimmune inflammatory foci. The specific expression of VSIG4 on resting
      macrophages in tissue suggests that this inhibitory ligand may be important for
      the maintenance of T cell unresponsiveness in healthy tissues.

PMID- 17016565
TI  - Copper(II) complexes of terminally protected pentapeptides containing three
      histidyl residues in alternating positions, Ac-His-Xaa-His-Yaa-His-NH2.
AB  - Copper(II) complexes of the pentapeptides Ac-HisAlaHisValHis-NH2, Ac
      HisValHisAlaHis-NH2, Ac-HisProHisAlaHis-NH2, Ac-HisAlaHisProHis-NH2, Ac
      HisGlyHisValHis-NH2 and Ac-HisValHisGlyHis-NH2 have been studied by
      potentiometric, UV-Vis, CD and EPR spectroscopic methods. It has been found that
      the pentapeptides are efficient ligands for the complexation with copper(II) and
      exhibit an outstanding versatility in the co-ordination geometry of complexes.
      The presence of three histidyl residues provides a high possibility for the
      formation of macrochelates via the exclusive binding of imidazole-N donor atoms.
      The macrochelation suppresses, but cannot preclude the deprotonation and metal
      ion co-ordination of amide functions and the species [CuH(-2)L] and [Cu2H(-4)L]
      predominate at physiological pH in equimolar solutions and in the presence of
      excess metal ions, respectively. It is also clear from the data that both C
      terminal and internal histidyl residues can work as the anchoring sites for metal
      binding and subsequent amide deprotonation resulting in the formation of co
      ordination isomers and dinuclear species in equimolar solutions and in the
      presence of excess metal ions, respectively. In more alkaline solutions (pH
      approximately 10) a third amide function can be deprotonated and co-ordinated in
      the species [CuH(-3)L]- with (N-,N-,N-,N(im)) co-ordination. The dinuclear
      species [Cu2H(-5)L]- and [Cu2H(-6)L](2-) containing hydroxide ions and/or
      imidazolato bridges are formed at high pH in the presence of excess of metal
      ions. The insertion of one proline into the sequence preceding histidyl residues
      hinders the deprotonation of amide functions at that site and the formation of
      only mononuclear complexes was observed with these peptides.

PMID- 17016566
TI  - Structural study of trivalent lanthanide and actinide complexes formed upon
      solvent extraction.
AB  - The coordination of the trivalent 4f ions, Ln = Nd3+, Eu3+ and Yb3+, as well as
      the trivalent 5f ion, Am3+, with diamide and dialkylphosphoric acid extractants,
      individually and in combination, was studied by use of X-ray absorption
      spectroscopy. These studies provide metrical information about the interatomic
      interactions between the f-ions (M3+) and the ligands, dihexylphosphoric acid
      (HDHP) and N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide (DMDOHEMA), that is of
      practical relevance to the control of metal-ligand binding in liquid-liquid
      extraction systems for the separation of trivalent actinide ions, An3+, from
      trivalent lanthanide ions, Ln3+. Through systematic variations of extraction
      conditions and extractant combinations, we have found that the HDHP complexes
      with M3+ involve MO6 coordination and distant M...P interactions, whereas the
      DMDOHEMA complexes with M3+ involve MO8 coordination. The combination of the
      EXAFS results with ancillary extraction data and IR results facilitates
      descriptions of the stoichiometries and structures of the molecular species
      formed in solution upon liquid-liquid extraction and leads to a new understanding
      of the binary extraction systems in terms of the strength and selectivity of An3+
      vs. Ln3+-ligand interactions. This fundamental structure information affords
      insight into solvent extraction processes that are of contemporary and practical
      importance in heavy element chemistry and to environmentally related issues
      arising from the separation and disposal of radioactive materials, particularly
      actinides and selected fission products, in the field of nuclear waste
      reprocessing research.

PMID- 17016567
TI  - Homochiral porous solids based on 1D coordination polymers built from 46-membered
      macrocycles.
AB  - Six homochiral coordination polymers 1-6 based on an enantiopure elongated and
      bent bipyridine ligand were synthesized and characterized by single-crystal X-ray
      diffraction studies. The framework structures of all six compounds were built up
      from similar 1D polymeric chains composed of 46-membered metallomacrocycles. Four
      distinct packing patterns were observed for this family of coordination polymers.
      With the exception of 1, the anions do not coordinate to the metal centers and
      reside in the open channels. Single-crystal X-ray diffraction studies show that
      the structures of these coordination polymers are sensitive to the anions even
      though they do not coordinate to the metal centers. The framework structures are
      somewhat tolerant of the change of metal centers and their local coordination
      environments. Gas sorption measurements on 1 suggest that chiral porous solids
      can be obtained with the present 1D coordination polymeric building blocks.

PMID- 17016568
TI  - Proton sponge phosphines: electrospray-active ligands.
AB  - Attachment of a proton sponge to a phosphine ligand renders neutral complexes of
      the ligand highly amenable to analysis by electrospray ionisation mass
      spectrometry (ESI-MS). The ligand 1,8-bis(dimethylamino)naphthyldiphenylphosphine
      (3) is extremely efficient and highly selective in forming exclusively [M + H]+
      ions, which may be detected at very low concentration. Ionisation efficiency of 3
      in the presence of H+ approached 100%. The bis-substituted ligand bis{1,8
      bis(dimethylamino)naphthyl}phenylphosphine (4) was also prepared and
      characterised, as were Fe(CO)4- (5c), Mn(eta5-C5H4Me)(CO)2- (6) and W(CO)5- (7)
      complexes of 3. Compounds 3, 3.HBr.EtOH, 4 and 5c were all structurally
      characterised.

PMID- 17016569
TI  - Aurolysis of alpha-C-deprotonated group 6 aminocarbene and thiocarbene complexes
      with Ph3PAu+.
AB  - Deprotonated Fischer-type aminocarbene complexes, (CO)5M=C(NR2)CH3 (M = Cr or W;
      R = Me or propyl), react with Ph3PAu+ by metal group substitution - (CO)5M for
      Ph3PAu+--and attachment of the extricated M(CO)5 to the deprotonated methyl
      group. (The products may also be seen as aminovinylgold compounds coordinated to
      M(CO)5 moieties.) DFT calculations at the B3LYP level of theory using model
      compounds indicate a clear preference of the gold unit for central C to terminal
      coordination in the ligand [NMe2CCH2]-, whereas the Cr(CO)5 has a 7 kcal mol(-1)
      preference for C(vinyl) coordination compared to N-coordination. In related
      thiocarbenes, the sulfur donor atom should be the preferred point of attachment
      for the metal carbonyl unit. The latter prediction is borne out in practice, and
      in the three products isolated, including Ph3PAu{C(=CH2)SPh}Cr(CO)5 in a mixed
      crystal with [Ph3PAuSPh]Cr(CO)5, precisely this coordination mode is present. The
      latter component of the mixed crystal has also been prepared independently of the
      vinyl one.

PMID- 17016570
TI  - Ligand controlled dioxygen oxidation of rhenium nitrosyl complexes.
AB  - The addition of an excess of phenyldiazomethane to chlorobenzene solutions of the
      cationic dinitrosyl bisphosphine rhenium(-I) complexes [Re(NO)2(PR3)2][BAr(F)4]
      (R = Cy 1a, R = (i)Pr 1b) gave the corresponding benzylidene complexes
      [Re{=CH(C6H5)}(NO)2(PR3)2][BAr(F)4] (2a and 2b) in good yields. The treatment of
      2b with dioxygen resulted in the oxidation of one of the nitrosyl ligands into
      the corresponding eta2-nitrito (3b) and nitrato complexes (4b) both in the solid
      state and in solution. In the case of the tricyclohexylphosphine derivative 2a
      the analogous conversion was not observed. A mechanism for the reaction of 2b
      with O2 is proposed which is based on an initial SET to the O2 molecule and
      subsequent formation of a peroxynitrite complex followed by the formation of a
      dinuclear mU-N2O4 intermediate. This in turn would undergo fission of the peroxo
      bond to afford 3b. A related sequence of steps is anticipated for the
      transformation of 3b to 4b. Furthermore, a similar mechanism seems reasonable for
      the seemingly topochemical reaction of 2b to 3b and 4b in the solid state. The
      initial SET to dioxygen and subsequent formation of the peroxynitrite complex is
      supported by DFT calculations on the trimethylphosphine model complexes
      [Re=CH{C6H5})(NO)2(PMe3)2]n+ (n = 1 and 2).

PMID- 17016571
TI  - Bio-inspired, side-on attachment of a ruthenium photosensitizer to an iron
      hydrogenase active site model.
AB  - The first ruthenium-diiron complex [(mu-pdt)Fe2(CO)5{PPh2(C6H4CCbpy)}Ru(bpy)2]2+
      1 (pdt = propyldithiolate, bpy = 2,2'-bipyridine) is described in which the
      photoactive ruthenium trisbipyridyl unit is linked to a model of the iron
      hydrogenase active site by a ligand directly attached to one of the iron centers.
      Electrochemical and photophysical studies show that the light-induced MLCT
      excited state of the title complex is localized towards the potential diiron
      acceptor unit. However, the relatively mild potential required for the reduction
      of the acetylenic bipyridine together with the easily oxidized diiron portion
      leads to a reductive quenching of the excited state, instead. This process
      results in a transiently oxidized diiron unit which may explain the surprisingly
      high light sensitivity of complex 1.

PMID- 17016572
TI  - The telomerisation of 1,3-butadiene and carbon dioxide: process development and
      optimisation in a continuous miniplant.
AB  - The telomerisation of 1,3-butadiene and carbon dioxide is one of the first
      homogeneously catalyzed reactions using carbon dioxide as a C1-building block. In
      this article we describe the process development for a miniplant applying this
      telomerisation in a continuous scale. Through repeated optimisation of the plant
      setup combined with parallel laboratory batch experiments the overall space-time
      yield of the plant was enhanced significantly.

PMID- 17016573
TI  - Synthesis of a chelating hexadentate ligand with a P3N3 donor set. Crystal and
      molecular structure of [OC-6-22]-[Co{(RP*,RP*,RP*)-CH3C(CH2PPhC6H4NH2
      2)3}](PF6)3.
AB  - The first structurally authenticated example of a hexadentate chelating tertiary
      phosphine in which all six donors are bound to a single metal centre is
      described. The multidentate ligand (RP*,RP*,RP*)- and (RP*,RP*,SP*)
      CH3C(CH2PPhC6H4NH2-2)3 has been prepared in 80% yield via the reaction of five
      equivalents of sodium (2-aminophenyl)phenylphosphide (generated in situ from (2
      aminophenyl)phenylphosphine and sodium in thf) with 1,1,1-tri(bromomethyl)ethane
      in thf. The diastereomeric mixture has been complexed to cobalt(III) and the
      resulting pair of complexes, viz. [Co{(RP*,RP*,RP*)-CH3C(CH2PPhC6H4NH2-2)3}]Cl3
      and [CoCl{(RP*,RP*,SP*)-CH3C(CH2PPhC6H4NH2-2)3}]Cl2, separated by ion exchange
      chromatography. The structure of the former (as the corresponding
      hexafluorophosphate salt) has been confirmed by X-ray crystallography and clearly
      shows all six donors of the P3N3 ligand coordinated to a single cobalt(III)
      centre. The related hexadentate ligand with internal N donors and terminal
      diphenylphosphino groups, viz. CH3C(CH2NHC6H4PPh2-2)3, has also been synthesised,
      albeit in low yield, via the reaction of [Li(tmeda)][2-NHC6H4PPh2] (generated in
      situ from (2-aminophenyl)diphenylphosphine, n-butyllithium and tmeda in diethyl
      ether) with 1,1,1-tri(iodomethyl)ethane in thf. No formation of a P3N3 ligand has
      been observed when either Na[2-PPhC6H4NH2] or [Li(tmeda)][2-NHC6H4PPh2] is
      reacted with the related tripodal substrate 1,1,1-tris(tolyl-4
      sulfonyloxymethyl)ethane in thf. Rather the P-methyloxetane (+/-)-[3-{(2
      aminophenyl)phenylphosphinomethyl}]-3-methyloxetane and the sulfonamide 2-(4
      CH3C6H4SO2)NHC6H4PPh2 and the corresponding N-methyloxetane [3-{(2
      diphenylphosphinophenyl)aminomethyl}]-3-methyloxetane have been isolated from the
      respective reactions. The structure of the sulfonamide has been confirmed by an X
      ray analysis of the platinum(II) complex trans-[PtCl(CH3){2
      PPh2C6H4NH(SO2C6H4CH(3-4)}2].

PMID- 17016574
TI  - Strong reducing agents containing dimolybdenum Mo2(4+) units and their oxidized
      cations with Mo2(5+/6+) cores stabilized by bicyclic guanidinate anions with a
      seven-membered ring.
AB  - The syntheses of two analogues of the bicyclic guanidinate ligand hpp (hpp = the
      anion of the guanidine-type compound 1,3,4,6,7,8-hexahydro-2H
      pyrimido[1,2a]pyrimidine) which contain two fused rings are reported. Each
      compound contains one seven-membered ring while the other is either a five (Htbd)
      or a six (Htbu) membered ring. In THF/Bu4NPF6, the dimolybdenum compounds
      Mo2(tbd)4 and Mo2(tbu)4 are easily oxidized and they have signals in the
      differential pulse voltammograms at -1.059 and -1.009 V (vs. Ag/AgCl),
      respectively and for the Mo2(5+/6+) couples and in the same order -0.242 and 
      0.312 V for the Mo2(6+/5+) couples. The two compounds produce the corresponding
      Mo2(bicyclic guanidinate)4Cl compounds immediately upon dissolution in CH2Cl2 and
      these easily form species with Mo2(6+) cores. In Mo2(tbd)4Cl there are two
      crystallographically independent molecules with Mo-Mo distances of 2.1711(7) and
      2.1690(7) A. The distance between metal atoms increases to 2.206(1) A upon
      oxidation to Mo2(tbd)4Cl2 which has a triply bonded Mo2(6+) core. For the
      diamagnetic compound Mo2(tbu)4 this distance is 2.0677(9) A and it increases to
      2.133(2) A upon reduction of the bond order from 4 to 3.5 in the paramagnetic
      compound Mo2(tbu)4Cl.

PMID- 17016575
TI  - Anticancer effect of lysine, proline, arginine, ascorbic acid and green tea
      extract on human renal adenocarcinoma line 786-0.
AB  - Five-year survival is limited to 60% in renal cancer patients at diagnosis. Due
      to the cancer's resistance to conventional treatments and associated high
      morbidity, we investigated the antimetastatic effects of a specific nutrient
      mixture (NM) containing lysine, proline, arginine, ascorbic acid and green tea
      extract on human renal adenocarcinoma cell line 786-0 by measuring: cell
      proliferation, modulation of MMP-2 and -9 secretion, and cancer cell invasive
      potential. Human renal cancer cell line 786-0 (ATCC) was grown in RPMI medium in
      24-well tissue culture plates. At near confluence, the cells were treated with
      NM, dissolved in media, and tested at 0, 10, 50, 100, 500 and 1000 microg/ml in
      triplicate at each dose. Cells were also treated with PMA 200 ng/ml to study
      enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP
      secretion by gelatinase zymography, and invasion through Matrigel. Zymography
      demonstrated MMP-2 and MMP-9 secretion by uninduced renal cancer cells with
      enhanced MMP-9 induced by PMA (200 ng/ml) treatment. NM inhibited the secretion
      of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-2
      at 500-microg/ml concentration and MMP-9 at 100 microg/ml. The invasion of renal
      cancer cells through Matrigel was totally inhibited (p=0.0001) by NM at 1000
      microg/ml concentration. Our results support a potential role for the nutrient
      mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2
      and MMP-9 secretion and invasion.

PMID- 17016576
TI  - The genetic differences between gallbladder and bile duct cancer cell lines.
AB  - Biliary tract cancers carry dismal prognoses. It is commonly understood that
      chromosomal aberrations in cancer cells have prognostic and therapeutic
      implications. However, in biliary tract cancers the genetic changes have not yet
      been sufficiently studied. The aim of this study was to clarify the presence of
      mutations in specific chromosomal regions that are likely to harbor previously
      unknown genes with a significant role in the genesis of biliary tract cancer. The
      recently developed bacterial artificial chromosome (BAC) array comparative
      genomic hybridization (CGH) can facilitate detail analysis with high resolution
      and sensitivity. We applied this to 12 cancer cell lines of the gallbladder (GBC)
      and the bile duct (BDC) using a genome-wide scanning array. Cell line DNA was
      labeled with green colored Cy5 and reference DNA derived from normal human
      leucocytes was labeled with red colored Cy3. GBC, as well as BDC cell lines, have
      shown DNA copy number abnormalities (gain or loss). In each of the seven GBC cell
      lines, the DNA copy number was gained on 6p21.32 and was lost on 3p22.3, 3p14.2,
      3p14.3, 4q13.1, 22q11.21, 22q11.23, respectively. In five BDC cell lines, there
      were DNA copy number gains on 7p21.1, 7p21.2, 17q23.2, 20q13.2 and losses were on
      1p36.21, 4q25, 6q16.1, 18q21.31, 18q21.33, respectively. The largest region of
      gain was observed on 13q14.3-q21.32 ( approximately 11 Mb) and of loss on 18q12.2
      q21.1 ( approximately 15 Mb), respectively. Both GBC and BDC cell lines have DNA
      copy number abnormalities of gains and/or losses on every chromosome. We were
      able to determine the genetic differences between gallbladder and bile duct
      cancer cell lines. BAC array CGH has a powerful potential application in the
      screening for DNA copy number abnormalities in cancer cell lines and tumors.

PMID- 17016577
TI  - Aberrant promoter hypermethylation profile of cell cycle regulatory genes in
      malignant astrocytomas.
AB  - Aberrant hypermethylation of the CpG islands in the promoter region plays a
      casual role in the inactivation of various key genes involved in the cell cycle
      regulatory cascade, which could result in loss of cell cycle control. The aim of
      the present study was to investigate the role of promoter methylation of genes
      with a proven involvement in the cell cycle regulation of malignant astrocytomas.
      We profiled the CpG island methylation status of the RB1, p14ARF, p15INK4b,
      p16INK4a, p21Waf1/Cip1, p27Kip1, and p73 genes by methylation-specific polymerase
      chain reaction assay in a homogeneous cohort of patients with malignant
      astrocytomas, and assessed their relationships with clinical behavior. Promoter
      hypermethylation of the RB1, p14ARF, p15INK4b, p16INK4a, p21Waf1/Cip1, p27Kip1,
      and p73 genes was detected in 3 (6%), 7 (13%), 4 (7%), 2 (4%), 1 (2%), 3 (6%),
      and 12 samples (22%) among 54 newly diagnosed malignant astrocytomas,
      respectively. A total of 50% of the cases carried methylation of at least one
      gene, and only 9% of the cases displayed concordant hypermethylation of two
      genes. None of the tumors disclosed three or more methylated loci. The presence
      of methylation of these genes or a group of genes was not associated with any
      distinct clinicopathological characteristics including tumor grade, proliferation
      activity, responsiveness to adjuvant therapy, or patient survival. p73 protein
      accumulation was demonstrated by immunohistochemical staining in 6 (15%) of the
      40 samples examined, with no significant association with the methylation status
      of p73 and any of the clinicopathological parameters tested. Our results
      demonstrated that a significant fraction of malignant astrocytomas displayed at
      least one methylated locus of the key cell cycle-related genes, although the
      genes were rarely hypermethylated, independent of the clinicopathological
      parameters. Thus, this epigenetic change is unlikely to play an important role in
      the evolution and development of malignant astrocytomas.

PMID- 17016578
TI  - Sequential endoscopic findings and histological changes of N
      nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.
AB  - We performed a sequential endoscopic examination of esophageal carcinogenesis
      induced by N-nitrosomethyl-benzylamine (NMBA) in F344 rats. The endoscopic
      findings were consistent with the histological changes observed in the specimens
      obtained by a biopsy and/or an autopsy. Seven-week-old male F344 rats received a
      weekly subcutaneous injection of 0.5 mg/kg NMBA for 15 weeks. The first
      endoscopic change that was detected was redness of the musosa due to the
      dilatation of the submucosal blood vessels. Subsequently, the mucosal redness
      became obscure, and we observed a focal loss of the visible blood vessel network
      due to hyperkeratosis, followed by the appearance of plaque-like elevated lesions
      due to acanthosis. Then, smooth and irregular polyps appeared as a result of the
      development of papilloma without or with dysplastic potential, respectively.
      Finally, rough elevation appeared as a result of carcinoma in situ and invasive
      squamous cell carcinoma. The present endoscopic findings correlated closely with
      the histological changes, indicating that sequential fiberscopic examination may
      be useful for monitoring esophageal carcinogenesis.

PMID- 17016579
TI  - Irinotecan cytotoxicity does not necessarily depend on the UGT1A1 polymorphism
      but on fluoropyrimidine: a molecular case report.
AB  - We have previously demonstrated that the combined use of doxifluridine and
      irinotecan shows a different molecular mechanism than that of the protracted
      venous infusion of 5-FU and irinotecan. In this analysis, there is a suggestion
      that doxifluridine may enhance irinotecan and enable us to decrease the dose of
      irinotecan without losing the strong effect by using doxifluridine instead of 5
      FU. We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28)
      as a known high risk for irinotecan, who was treated with a combination of
      doxifluridine and irinotecan for peritoneal dissemination resulting in stable
      disease for 2 years without adverse reactions, although the patient initially
      developed severe adverse effects to the combination of the protracted venous
      infusion of 5-FU and irinotecan. Even with the same ratios of fluoropyrimidine
      and irinotecan combinations, replacing 5-FU with doxifluridine or capecitabine
      could provide new strategies to obtain not only convenience but also better
      efficacy and safety at the molecular level.

PMID- 17016580
TI  - Preferentially enhanced gene expression from a synthetic human telomerase reverse
      transcriptase promoter in human cancer cells.
AB  - Although the human telomerase reverse transcriptase (hTERT) promoter can regulate
      cancer-specific genes, it is generally too weak to be effective. We therefore
      attempted to improve the potency of synthetic hTERT promoters by fusing the core
      element (E) of the hTERT promoter (H) and the tripartite leader sequence (T) from
      human adenovirus 5 in a combinatorial manner. To determine the potential as
      cancer-specific promoters, we measured luciferase activity driven by the chimeric
      hTERT promoters in human cancer cells. Among various constructs, the E3-H-T
      promoter induced the strongest luciferase activity in all the tested cancer
      cells. SK-Hep1 and Hela cells experienced 1000- and 11-fold higher expression
      than the basic hTERT promoter, respectively. Relative to the SV40 universal
      promoter, the E3-H-T promoter led to higher levels of gene expression. Using
      EMSA, we found that the hTERT enhancer region was specifically bound to c-Myc and
      Sp1. Thus, the data suggest that the E3-H-T promoter with up-regulated cancer
      specific gene expression could be useful in cancer gene therapy.

PMID- 17016581
TI  - Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for
      diagnosis of patients with non-small cell lung cancer.
AB  - Research on molecular mechanisms underlying the carcinogenesis of non-small cell
      lung cancer (NSCLC) may provide gene targets in critical pathways valuable for
      improving the efficacy of therapy and survival of patients with NSCLC. However,
      the molecular markers highly sensitive for the prognosis and treatment evaluation
      of NSCLC are not yet available. To explore candidates, we conducted an
      oligonucleotide microarray study with three pairs of NSCLC and normal lung
      tissue, and determined 8 differentially expressed genes including the Human MutT
      homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2
      (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit
      (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun
      X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also
      incorporated for further analysis. The expression profiles of the twelve genes in
      seventy pairs of NSCLC tumor and normal lung tissue were then detected
      quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR).
      The data of the membrane array and qRT-PCR were compared for consistency and the
      potential of these mRNA markers in clinical application. The results showed that
      membrane array and qRT-PCR obtained consistent data for the tested genes in both
      sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For
      patients' clinicopathological characteristics, the overexpression of hMTH1, SPD,
      HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the
      pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD,
      ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis.
      This is the first report relating SPD to a prognosis marker for NSCLC. Moreover,
      the combined detection of these four mRNA markers by membrane array had a
      sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than
      these markers had achieved separately. In conclusion, we identified mRNA markers
      for NSCLC prognosis and therapy evaluation from differentially expressed genes
      determined by using micro-array. Further studies are needed to collect the data
      of the mRNA markers used in clinical practice.

PMID- 17016582
TI  - Catalpa seed oil rich in 9t,11t,13c-conjugated linolenic acid suppresses the
      development of colonic aberrant crypt foci induced by azoxymethane in rats.
AB  - Catalpa (Catalpa ovata) seed oil (CPO) is a unique oil that contains a high
      amount of 9trans,11trans,13cis-conjugated linolenic acid. In the present study,
      we investigated whether dietary administration with CPO affects the development
      of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats
      to elucidate its possible cancer chemopreventive efficiency. Also, the effect of
      CPO on the fatty acid composition of liver tissue and colonic mucosa, the serum
      levels of total cholesterol and triglyceride, and the mRNA expression of
      cyclooxygenase (COX)-2 in the colonic mucosa were measured. In addition, the cell
      proliferation activity and apoptotic index in the colonic mucosa were estimated
      immunohistochemically. Animals were given two weekly subcutaneous injections of
      AOM (20 mg/kg body weight). They also received the experimental diet containing
      0.01%, 0.1% or 1% CPO for 4 weeks, starting one week before the first dosing of
      AOM. AOM exposure produced a substantial number of ACF (99+/-28) at the end of
      the study (week 4). Dietary administration of CPO reduced the number of ACF (AOM
      + 0.01% CPO, 32+/-11, P<0.001; AOM + 0.1% CPO, 35+/-18, P<0.001; AOM + 1% CPO,
      18+/-10, P<0.001). 9t,11t-conjugated linoleic acid was detected in the liver
      tissue and colonic mucosa of rats fed the CPO-containing diet. Additionally,
      dietary administration with CPO decreased the serum triglyceride level and the
      expression of COX-2 mRNA in the colonic mucosa. The indices of cell proliferation
      and apoptosis in the colonic mucosa of rats treated with AOM and 1% CPO have
      significant differences when compared with the AOM alone group. These findings
      suggest the possible chemopreventive activity of CPO in the early phase of colon
      carcinogenesis.

PMID- 17016583
TI  - Characterization of mitochondria in cisplatin-resistant human ovarian carcinoma
      cells.
AB  - One of the mechanisms of cisplatin cell cytotoxicity is the mitochondria
      associated induction of apoptosis. The morphological or functional change of
      mitochondria in cisplatin-resistant cells has already been reported. Herein we
      present additional data describing the mitochondrial genomic and functional
      changes in cisplatin- resistant cells. Cisplatin increased the level of apoptotic
      cells in cisplatin-sensitive human ovarian carcinoma OV 2008 and C13 cells by
      3.90+/-1.01 (SD; N=3) (p<0.01)-fold and 2.03+/-0.20 (SD; N=3) (p<0.01)-fold
      compared to the basal apoptotic level. This indicates a lower level induction of
      apoptosis by 50% in cisplatin-resistant OV 2008/C13 *5.25 variant (C13) cells. In
      both cell types, cisplatin cytotoxicity is mostly inhibited by the caspase-9
      inhibitor as well as the caspase-3 inhibitor, Ac-DEVD-CHO, suggesting that the
      mitochondrial downstream event was functioning well in both the C13 cells and in
      OV 2008 cells. Mitochondrial transmembrane potential (DeltaPsim) determined by
      flow cytometry using DiOC6-stained cells revealed a significant depolarization of
      C13 cells as compared to OV 2008 cells. Treatment of these cells with cisplatin
      or hydrogen peroxide induces complete mitochondrial DNA damage in OV 2008 cells,
      while only partial DNA-destruction is observed in C13 cells, strongly suggesting
      that mitochondria are resistant to cisplatin and oxidative stress response.
      Continuous oxygen consumption of these cells monitored by a multi-channel
      dissolved oxygen meter is 1.70-fold higher in OV 2008 cells than C13 cells and
      the oxygen consumption was decreased by 30% in C13 cells, suggesting
      mitochondrial respiratory malfunction in these cells. The hypothesis generated
      here is that mitochondrial DNA resistance to cisplatin and oxidative stress
      response might be one of the main characteristics concerning the lower level of
      apoptosis induced by cisplatin. However, the mechanism by which the mitochondrial
      DNA encoded molecule is involved in cisplatin resistance remains to be
      determined.

PMID- 17016584
TI  - Overexpression of PAX5 in oral carcinogenesis.
AB  - The oncogenic transcription factor PAX5 is an important developmental regulator
      and is implicated in the pathogenesis of several malignancies. The PAX5 gene is
      involved in medulloblastoma, non-Hodgkin's lymphoma, transitional cell carcinoma
      of the bladder, neuroblastoma, breast cancer and SCC. In the current study, to
      determine the potential involvement of PAX5 in oral squamous-cell carcinoma
      (OSCC) and leukoplakias, we evaluated the status of PAX5 mRNA and protein
      expression in OSCC cell lines, human primary OSCCs, and leukoplakias by real-time
      quantitative reverse transcriptase-polymerase chain reaction, Western blot
      analysis, and immunohistochemistry. A significant increase in PAX5 expression was
      observed in all OSCC-derived cell lines examined compared to human normal oral
      keratinocytes (HNOKs). In immunohistochemistry, 78% of tumors and 42% of
      leukoplakias examined were positive for PAX5, while no immunoreaction was
      observed in corresponding normal tissues. The results suggest that PAX5 plays an
      important role during oral carcinogenesis, especially in the early stage, and
      that the gene may have potential as a biomarker and therapeutic target for OSCC.

PMID- 17016585
TI  - Gene expression pattern in oral cancer cervical lymph node metastasis.
AB  - Treatment protocols for malignant tumors in the oral cavity differ greatly based
      on the presence of cervical lymph node metastasis. We applied gene expression
      profiling to the pathological lymph node status and used a training-test approach
      to evaluate the reliability of cDNA microarray-based classifications of 15
      matched resected primary oral squamous cell carcinomas (OSCCs) and corresponding
      normal oral tissues. The clustering of all the microarray data was separated into
      two groups based on metastatic node positivity and node negativity. Furthermore,
      a 20-gene signature was identified that differentiated the testing set (n=8) with
      high classification accuracy (88%). Our findings support the hypothesis that the
      lymph node metastasis status can be predicted using the gene expression patterns
      of the primary OSCC, and may be a powerful tool in identifying patients at high
      risk of lymph node metastasis.

PMID- 17016586
TI  - PAX8 expression in human bladder cancer.
AB  - PAX8 is a transcription factor with a role in ontogenesis of the urinary tract.
      The aim of the present investigation was to investigate PAX8 expression in normal
      bladder and in non-invasive urothelial tumours. Nine cases of normal urothelial
      mucosa, 2 cases of papillary urothelial neoplasia of low malignant potential, 12
      cases of low grade non-invasive papillary urothelial carcinoma and 16 cases of
      high grade non-invasive papillary urothelial carcinoma were investigated by
      immunohistochemistry. PAX8 mRNA expression was evaluated by RT-PCR in a different
      set of normal bladder mucosas and tumours. In addition, PAX8 expression was
      evaluated by RT-PCR in bladder from 2 human embryos and in several continuous
      cell lines derived from bladder tumours (5637, RT-112, TCC-SUP, HT 1376). In
      immunohistochemical studies, PAX8 was expressed in 28 out of 30 non-invasive
      urothelial tumours, but not in the normal adult bladders. In RT-PCR studies, PAX8
      was expressed in 13 out of 13 bladder tumours but not in the 6 normal bladder
      mucosa. Contrary to that in adults, PAX8 was expressed in 2 cases of bladder
      mucosa from 16-week-old embryos. PAX8 was expressed in all the cell lines from
      bladder tumours. Both in the bladder tumours and cell lines PAX8 expression was
      highly heterogeneous in terms of the splicing isoforms. Treatment of cell lines
      with sodium butyrate (NaB) induced several changes of the splicing isoforms.
      Therefore, only subsets of molecular events that determine the PAX8 mRNA splicing
      heterogeneity in bladder tumours are sensitive to NaB treatment.

PMID- 17016587
TI  - Histological type of oncogenity and expression of cell cycle genes in tumor cells
      from human mesenchymal stem cells.
AB  - In previous experiments, a novel tumor cell line, which was characterized by
      dominated F6 mutated from human mesenchymal stem cells (hMSCs), was developed.
      The mechanism and biological characteristics of this mutation are still unclear.
      In this study, the histological type of F6 cells was investigated by
      immunohistochemistry with specific markers: vimentin, CD117, desmin, NSE and vWF.
      The characteristics of proliferation and metastasis were shown by PCNA
      (proliferating cell nuclear antigen), and nm23 and cell cycle-related genes, such
      as p16, p21, p53 and pRb, were analyzed by RT-PCR and immunohistochemistry. The
      expression of hTRAP and BMI-1 were detected by real-time PCR and Western
      blotting. The activity of telomerase was analyzed by TRAP (telomerase repeat
      amplification protocol) assay. The results showed that multi-directional
      differentiation occurred in F6 cells, i.e., special markers of muscle,
      endothelial cell and nerve system were co-expressed in F6 cells, while hardly
      expressed in hMSCs. F6 cells maintained the same properties as of MSCs, such as
      negativity for both CD117 and vimentin. F6 cells exhibited strong positivity for
      PCNA and negativity for nm23. The cell cycle-related genes, such as p16, p21, p53
      and pRb, were not detected in F6 cells, while the expression of hTRAP and BMI-1
      was significantly higher. The activity of telomerase was also significantly
      higher in F6 cells than that in hMSCs. These findings indicated that multi
      directional differentiation occurred during the transformation of hMSCs into F6
      cells, and that the genes of cell cycle and cell senescence may also be
      associated with the neoplasia of adult stem cells.

PMID- 17016588
TI  - Significance of cyclin E and p27 expression in malignant ovarian germ cell
      tumors: correlation with the cell proliferation activity and clinicopathologic
      features.
AB  - Although elevated cell proliferation activity is one of the most remarkable
      features known to characterize malignant ovarian germ cell tumors (MOGCTs),
      abnormalities in cell cycle regulation have yet to be thoroughly investigated in
      MOGCTs. Forty-two MOGCTs were immunohistochemically examined to determine their
      cyclin E and p27Kip1 (p27) expression in correlation with their cell
      proliferation activity and clinicopathological features. Cytosine methylation of
      p27 gene promoter CpG islands was estimated by methylation-specific PCR. The
      labeling index (LI) was calculated as a percentage of the positively stained
      tumor cells per total tumor cells counted. p27 LIs showed a significant inverse
      correlation with Ki-67 LIs in MOGCTs examined (p<0.05). The cyclin E LIs of yolk
      sac tumors were significantly higher than those of dysgerminomas (p<0.01). Two
      MOGCTs were methylation-positive (5%). Both p27 and cyclin E are thought to be
      involved in the cell cycle regulation of MOGCTs. p27 gene promoter methylation is
      rare in MOGCTs. An immunohistochemical evaluation of cyclin E may be a useful
      diagnostic modality for differentiating MOGCTs.

PMID- 17016589
TI  - Interactive effect of genetic polymorphism of glutathione S-transferase M1 and
      smoking on squamous cell lung cancer risk in Korea.
AB  - To evaluate the role of the genetic polymorphisms of CYP2E1, GSTM1 and GSTT1, and
      their interaction with smoking in lung cancer development in Korean males, a
      hospital-based case-control study was conducted. Histologically confirmed male
      lung cancer patients (n=171) and male patients with no present or previous
      history of systemic illness who visited the urology department (n=196) were
      recruited from Seoul National University Hospital, Korea (1998-1999). CYP2E1
      genotypes were determined by PCR-RFLP using RsaI digestion and GSTM1 and T1
      genotypes were determined by multiplex PCR. Risks were estimated as odds ratios
      (ORs) and 95% confidence intervals (CIs) using a logistic regression model
      adjusting for age and pack-year. Smoking was a significant risk factor for lung
      cancer (P<0.001). Although genetic polymorphisms of CYP2E1, GSTM1 and T1 were not
      associated with the overall risk of lung cancer, the GSTM1 null genotype
      significantly increased the risk of squamous cell lung cancer (OR=1.9, 95%
      CI=1.04-3.60). An interactive effect between the GSTM1 null genotype and smoking
      was observed (P=0.04). These results suggest that the GSTM1 null genotype is
      associated with squamous cell lung cancer and modifies the effect of smoking on
      squamous cell lung cancer development in Korean males.

PMID- 17016590
TI  - Clinicoprognostical features of endometrial cancer patients with somatic mtDNA
      mutations.
AB  - Somatic mitochondrial DNA (mtDNA) mutations have been found in a subset of
      endometrial cancers (EC) from different populations. We have investigated the
      relationship between mtDNA changes and clinical and pathological variables of
      women affected by EC. mtDNA mutations were detected both in early (3/32; 9%) and
      in advanced (1/8; 12%) stages of uterine tumors. However, patients carrying the
      mtDNA mutations or the normal mtDNA sequence had indistinguishable
      clinicopathological data, including age, clinical stage, histological grade and
      type or depth of myometrial invasion. It is noteworthy that mtDNA mutations were
      not detected in hyperplastic endometrial tissues or in ECs coexisting with
      hyperplasia, nor in a single case of endometrial stromal sarcoma. LOH at the
      tumor suppressor genes RB1 and TP53 as well as p16INK4A alterations (LOH, gene
      deletion) were found in tumors carrying mtDNA mutations. These results suggest
      that somatic mtDNA mutations are detected in a subset of ECs, although they are
      unrelated to clinicopathological variables of cancer.

PMID- 17016591
TI  - Histone deacetylase inhibitors induce cell death in supratentorial primitive
      neuroectodermal tumor cells.
AB  - Histone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic
      agents with the capacity to induce differentiation and/or apoptosis of cancer
      cells. The objective of this study was to evaluate the activity of HDIs against
      supratentorial primitive neuroectodermal tumor (sPNET) cells. We show that the
      HDIs, suberoylanilide hydroxamic acid, sodium butyrate, and trichostatin A,
      induced cell death, and activated caspase-3 and -9 in a sPNET cell line, PFSK.
      The poly-caspase inhibitor z-VAD-fmk partially prevented the action of HDIs, as
      judged by determining the mitochondrial membrane potential and by quantifying
      internucleosomal DNA fragmentation. In conclusion, the HDIs explored possess
      potent activity against sPNET cells, suggesting that HDIs may be effective in the
      treatment of sPNET.

PMID- 17016592
TI  - Array-based comparative genomic hybridization of circulating esophageal tumor
      cells.
AB  - Esophageal squamous cell carcinoma (ESCC) shows a high frequency of lymphatic
      and/or systemic metastasis, even when the tumor invades only the submucosa. To
      investigate the genetic alterations in circulating esophageal tumor cells, we
      performed array-based comparative genomic hybridization (CGH) analysis of 8 DNA
      samples of xenografts, which were previously established from the thoracic duct
      lymph of 13 ESCC patients. A total of 5 loci (or genes), 10q21.3 (EGR2), 11q13.3
      (CCND1/CyclinD1, FGF4, and EMS1), 11q14 (PAK1), and 22qtel (ARSA) were found to
      be candidate amplified loci in the xenograft. In contrast, a total of 24 loci
      including 9p21 (p16 and MTAP) were found to be homozygously deleted candidates in
      the xenograft. Both p16 homozygous deletion and CCND1 amplification were detected
      in 6 (75%) and 5 (62.5%) of the 8 xenografts. Furthermore, by quantitative
      Southern blot analysis, we found p16 homozygous deletion in 30.8% (8/26) of the
      primary tumors and in 50% (4/8) of the metastasized lymph nodes. The frequency of
      CCND1 amplification and p16 homozygous deletion is suggested to be associated
      with ESCC progression. Matrigel invasion assays of p16-deleted ESCC cells showed
      that restoring wild-type p16 activity into the cells significantly inhibits tumor
      cell invasion, suggesting that p16 inactivation could be involved in ESCC
      invasion. This is the first report showing the genetic alteration of concealed
      tumor cells in the thoracic duct lymph. The present gene list should be helpful
      for identifying new amplified and deleted genes in primary ESCCs as well as in
      metastasized lymph nodes.

PMID- 17016593
TI  - Intraoperative pathological investigation of recurrent nerve nodal metastasis can
      guide the decision whether to perform cervical lymph node dissection in thoracic
      esophageal cancer.
AB  - Three-field lymph node dissection has been widely used to treat thoracic
      esophageal cancer, but is very invasive and can cause serious complications.
      Whether cervical lymph node dissection should be performed in all patients with
      thoracic esophageal cancer remains controversial. We pathologically examined the
      recurrent nerve lymph nodes during surgery in patients with thoracic esophageal
      cancer to determine the presence or absence of lymph node involvement. In
      patients without recurrent nerve nodal involvement, cervical lymph node
      dissection was not performed. Treatment outcomes were analyzed to evaluate
      whether intraoperative pathological investigation was a useful procedure. Among
      71 patients with thoracic esophageal cancer who underwent 3-field lymph node
      dissection, the rate of cervical lymph node metastasis was 40.9% in patients with
      recurrent nerve nodal metastasis on intraoperative pathological investigation, as
      compared with 10.2% in patients without recurrent nerve nodal metastasis
      (p=0.007). Multiple logistic-regression analysis showed that recurrent nerve
      nodal metastasis was a strong predictor of cervical lymph node metastasis (odds
      ratio, 2.98; 95% confidence interval, 1.139-7.775; p=0.03). Among 41 patients who
      underwent intraoperative pathological investigation, 10 had recurrent nerve nodal
      metastasis and underwent cervical lymph node dissection. Two of these patients
      had histological evidence of cervical lymph node metastasis. The remaining 31
      patients had no recurrent nerve nodal metastasis on intraoperative pathological
      examination and therefore did not receive cervical lymph node dissection. None of
      these patients had cervical lymph node recurrence on follow-up. We compared
      patients who underwent intraoperative pathological investigation with those who
      underwent conventional 3-field lymph node dissection (without performing
      intraoperative pathological investigation). The rates of cervical lymph node
      recurrence were similar among the groups (2.6% vs. 6.7%), but the 3-year survival
      rate was significantly higher in the patients who underwent intraoperative
      pathological dissection (83.3%) than in those who underwent 3-field dissection
      (57.2%; p<0.05). Although this was a retrospective study, our results suggest
      that outcomes of patients undergoing cervical lymph node dissection according to
      the results of intraoperative pathological investigation are at least as good as
      those in patients undergoing 3-field lymph node dissection. We conclude that
      intraoperative pathological investigation of recurrent nerve nodal metastasis is
      useful for determining whether cervical lymph node dissection should be performed
      in patients with thoracic esophageal cancer.

PMID- 17016594
TI  - Successful treatment of large-size advanced hepatocellular carcinoma by
      transarterial chemoembolization followed by the combination therapy of
      percutaneous ethanol-lipiodol injection and radiofrequency ablation.
AB  - We report a case of large-size hepatocellular carcinoma (HCC) successfully
      treated with transarterial chemoembolization (TACE) followed by the combination
      therapy of percutaneous ethanol-lipiodol injection and radiofrequency ablation
      (PELI-RFA) and percutaneous ethanol-lipiodol injection (PELI) therapy. In the
      present case, the patient had a large-size advanced HCC, 7 cm in diameter,
      located in the S8 region of the liver. In addition, the hepatic reserve of the
      patient was severely poor. In order not to impair the poor hepatic reserve, we
      chose PELI-RFA and PELI, originally developed in our department and reported as
      milder treatment modalities than others. After TACE , PELI-RFA and PELI were
      performed several times, the HCC was totally destroyed and early enhancement
      shown by helical dynamic computed tomography disappeared completely after
      treatment. The hepatic reserve of the patient was not impaired by the series of
      treatments. Serum levels of tumor markers, alpha-fetoprotein and Des-gamma
      carboxy prothrombin, were rapidly decreased to almost normal levels. PELI-RFA and
      PELI may be effective for the treatment of large-size HCC of patients with poor
      hepatic reserve.

PMID- 17016595
TI  - Increased expression of CENP-H gene in human oral squamous cell carcinomas
      harboring high-proliferative activity.
AB  - We examined the expression of Centromere protein H (CENP-H) mRNA in 38 oral
      squamous cell carcinomas (SCCs), 2 epithelial dysplasias and 5 normal gingivae
      using the real-time quantitative reverse transcription-polymerase chain reaction
      (RT-PCR). The mean expression level of CENP-H mRNA was higher in oral SCCs
      (0.11+/-0.08) than epithelial dysplasias (0.03+/-0.01) and normal gingivae
      (0.027+/-0.01). The expression level of CENP-H mRNA was significantly higher in
      oral SCCs than normal gingivae (Mann-Whitney U test, P=0.005). We also found a
      significant association between the level of CENP-H mRNA expression and clinical
      stage in oral SCCs (Mann-Whitney U test, P=0.04). We next studied the expression
      of CENP-H in 17 oral SCCs immunohistochemically. A significant correlation
      between the expression levels of CENP-H protein and the Ki-67 labeling index was
      found (Mann-Whitney U test, P=0.005). These results indicate that human CENP-H is
      closely linked to the increased or abnormal cell proliferation in malignant
      conditions.

PMID- 17016596
TI  - Cobrotoxin-containing analgesic compound to treat chronic moderate to severe
      cancer pain: results from a randomized, double-blind, cross-over study and from
      an open-label study.
AB  - Cobrotoxin produces intense analgesia but it has an onset of response of 1-3 h
      which hampers its clinical use in cancer pain. Recently, a compound analgesic
      formulation combining cobrotoxin, tramadol hydrochloride and ibuprofen (Compound
      Keluoqu, CKLQ) has become available in China. The aim of this study was to
      evaluate the clinical efficacy of CKLQ for moderate to severe cancer pain. A
      consecutive series of patients with chronic moderate to severe cancer pain was
      enrolled into two multicenter trials. Of the 230 eligible patients, 119 were
      assigned to a randomized, double-blind, cross-over study, while 111 entered an
      open-label study. They were all of Han-China nationality and had a mean age of
      52.0 and 55.4 years and a mean body weight of 55.6 and 52.9 kg, respectively. A
      total of 11 patients discontinued the study, 6 (54.5%) because of insufficient
      pain relief and 5 due to the occurrence of adverse events. In the cross-over
      study, 59 patients were randomized to receive a CKLQ package with 2 CKLQ tablets
      (each containing 0.16 mg cobrotoxin, 25 mg tramadol hydrochloride and 50 mg
      ibuprofen) and 2 placebo capsules, a placebo package with 2 placebo tablets and 2
      placebo capsules, and an active control package with 2 tramadol hydrochloride
      capsules (each containing 50 mg tramadol hydrochloride) and 2 placebo tablets
      (arm A), and 60 to receive a tramadol hydrochloride package, a placebo package
      and a CKLQ package (arm B), sequentially and only once. Patients in the open
      label study only received CKLQ and were given the option to continue for up to 7
      days as long as they had satisfactory pain relief. Pain response was classified
      as CR, PR and NC. CR was defined as 100% pain relief, with a pain score of 0 on a
      0-10 VAS. PR was defined as decreased to mild pain, with a pain score of no more
      than 4 on a 0-10 VAS. NC was defined as pain that either remained unchanged or
      that was reduced from severe to moderate at baseline, with a VAS pain score of
      more than 4 after treatment. One hundred and eight patients completed the cross
      over study with all the three drug units. The overall rate of pain relief was
      93/111 (83.7%) for CKLQ, 75/110 (68.2%) for tramadol hydrochloride (P=0.011) and
      39/111 (35.1%) for placebo (P<0.001). The mean duration of pain relief with CKLQ
      was significantly longer than that of the other two agents (P<0.001). Of the 35
      patients who did not respond to tramadol hydrochloride, 27 (77.1%) responded to
      CKLQ, while of the 18 who did not respond to CKLQ, 8 (55.6%) achieved
      satisfactory pain control with tramadol hydrochloride. In the open-label study,
      the overall relief rate of a single-dose of CKLQ was 99/111 (89.2%). A reduction
      in the percentage of complete relief, an increase in that of PR and a significant
      decrease in duration of relief were observed after continuous treatment with at
      least 10 doses of CKLQ. The frequency of adverse events for CKLQ was similar to
      that of tramadol hydrochloride. The results of the randomized, double-blind,
      cross-over study and the open-label study of CKLQ in cancer patients with chronic
      moderate to severe cancer pain suggest that the CKLQ may be valuable for the
      treatment of chronic moderate to severe cancer pain. However, the tolerance of
      CKLQ remains to be further defined.

PMID- 17016597
TI  - The optimal schedule for 5-fluorouracil radiosensitization in colon cancer cell
      lines.
AB  - To evaluate the optimal schedule of 5-fluorouracil (5-FU) radiosensitization in
      rectal cancer, we investigated the interaction between radiation and several
      doses of 5-FU on colon cancer cell lines based on pharmacokinetics of oral
      fluoropyrimidine. Cellular cytotoxicity in colon cancer cell lines, LoVo, WiDr
      and Caco-2 was determined, using a WST-8 colorimetric assay, after 24 h exposure
      to several concentrations of 5-FU and a radiation dose of 5 Gy. Cells were
      exposed to 5-FU 24 and 0 h before radiation. 5-FU doses were classified into
      three groups: uracil-tegafur (0.01-0.1 microM), S-1 (0.1-1.0 microM) and
      pharmacokinetic modulating chemotherapy (0.1-10 microM). In addition, the effect
      of 5-FU on the steady-state levels of a human excision repair cross-complementing
      1 gene and cell cycle distribution were examined. Regardless of time of 5-FU
      exposure, all cell growth was significantly inhibited in a dose-dependent manner.
      In Caco-2 cells, the cytotoxicity of radiation followed by 5-FU was significantly
      greater than that of 5-FU followed by radiation, unlike in the other cell lines.
      The growth inhibitory effect of radiation followed by 5-FU increased in a dose
      dependent manner to reach a plateau at S-1 doses in all cell lines. In cell cycle
      distribution, 5-FU exposure for 24 h increased the S phase fraction in a dose
      dependent manner. RT-PCR showed that 5-FU post-treatment graduallly inhibited
      mRNA expression of ERCC1, which may affect recombination repair efficiency,
      accounting for the higher tumor sensitivity. Oral fluoropyrimidines, like S-1,
      that can maintain a constant level of 5-FU may be an acceptable alternative
      radiosensitizer to protracted 5-FU infusion, when the aim of neoadjuvant
      chemoradiotherapy for rectal cancer is locoregional control.

PMID- 17016598
TI  - Expression level of ECT2 proto-oncogene correlates with prognosis in glioma
      patients.
AB  - The ECT2 (epithelial cell transforming sequence 2) proto-oncogene encodes a
      guanine nucleotide exchange factor for Rho GTPases, and regulates cytokinesis.
      ECT2 plays a critical role in Rho activation during cytokinesis, and thus may
      play a role in the pathogenesis of glioma. In this study, we investigated
      relationships between ECT2 expression, tumor histology, and prognosis in glioma
      patients. ECT2 mRNA expression was examined using quantitative real-time PCR,
      while its protein expression was examined by immunohistochemistry of 54 glioma
      tissue samples. Expressions of ECT2 mRNA and protein were markedly increased in
      high-grade gliomas compared to low-grade gliomas. Patients in whom expression of
      ECT2 mRNA and protein in tumor tissues was the lowest survived longer than
      patients who had higher expression. In vitro, ECT2 siRNA inhibited glioma cell
      proliferation and invasion. These data suggest that increased expression of ECT2
      contribute to promotion of tumor invasiveness and progression, implying that
      evaluation of ECT2 expression is a prognostic marker for glioma patients.

PMID- 17016599
TI  - p27KIP1 and GATA-1 are potential downstream molecules in activin A-induced
      differentiation and apoptosis pathways in CML cells.
AB  - p27KIP1 is known as a regulator of cellular differentiation and apoptosis in
      human cancer cells. We have previously reported that human chronic myeloid
      leukemia (CML) KU812 and K562 cells show inhibited cellular proliferation in
      response to treatment with activin A, a member of TGF-beta superfamily. Apoptosis
      and erythroid differentiation can be induced in KU812 and K562 cells,
      respectively. We report herein that activin A induced the expression of p27KIP1
      in CML cells along with the induction of cellular differentiation and apoptosis.
      There are putative binding sequences of erythroid-related transcription factor
      GATA-1 in the promoter region of the human p27KIP1 gene. Expression of GATA-1
      protein in activin A-treated KU812 and K562 cells showed dissimilar regulation in
      these two cell lines. Induction of p27KIP1 was commonly observed, but it did not
      correspond to the expression levels of GATA-1 in either line of activin A-treated
      CML cells. In addition, ERK protein was rapidly and transiently activated with
      activin A in both types of CML cells, suggesting that phosphorylation of ERK is
      required for activin A signaling in CML cells. These results indicate that both
      p27KIP1 induction and regulation of GATA-1 play essential roles in activin A
      induced erythroid differentiation and apoptosis.

PMID- 17016600
TI  - Humoral immune response to p16, a cyclin-dependent kinase inhibitor in human
      malignancies.
AB  - The p16 protein is a cyclin-dependent kinase (CDK) inhibitor, which plays an
      important role in the regulation of the cell cycle by inactivating the cyclin
      dependent kinase (CDK) that phosphorylates the retinoblastoma (Rb) protein.
      Overexpression of p16 protein has been found in many types of human malignancy.
      Autoantibody response to p16 in cancer has not been reported. This study
      determined the extent and frequency of autoantibodies to p16 in diverse
      malignancies. p16 recombinant protein was expressed in E. Coli BL21 (DE3) cells,
      and purified using GST fusion protein purification system. In further studies,
      p16 recombinant proteins were used as antigens in enzyme-linked immunoassay
      (ELISA) and Western blotting. Sera from 479 cancer patients and 82 normal
      individuals were analyzed. Autoantibodies to p16 were found in 11.7% in cancer,
      with significant difference from the normal individuals (p<0.05). The results in
      this study also showed that the frequency of antibodies to p16 is relatively
      higher in nasopharyngeal cancer (28.6%), breast cancer (17.1%) and hepatocellular
      carcinoma (HCC, 21.4%). Of the 56 ELISA positive sera with the anti-p16
      antibodies, 85.7% (48/56) had positive reactions in Western blotting. The antigen
      antibody absorption experiment was also performed to confirm the specificity of
      the anti-p16 antibody. In order to increase the frequency of antibody detection
      in cancer, a combination of three tumor-associated antigens (TAAs) p16, p53 and c
      myc were used. Increased frequencies at p<0.01 were found for antibodies to p16
      in breast, esophageal, and nasopharyngeal cancer as well as HCC. For antibodies
      to c-myc, increased frequencies at p<0.01 were found in breast, cervical,
      colorectal and lung cancer. For antibodies to p53, increased frequencies at
      p<0.01 were only found in breast cancer. With the successive addition of three
      TAAs, there was a stepwise increase of positive anti-body reaction up to 44% in
      breast cancer and 43% in nasopharyngeal cancer. In summary, the results in this
      study suggest that the combination of antibodies might acquire higher sensitivity
      for early cancer diagnosis. It is conceivable that auto-antibody profiles
      involving different panels or arrays of TAAs might be developed in the future and
      the results could be useful for cancer diagnosis.

PMID- 17016601
TI  - Genotype of thymidylate synthase likely to affect efficacy of adjuvant 5-FU based
      chemotherapy in colon cancer.
AB  - Thymidylate synthase [TS, (EC 2.1.1.45)] is the target enzyme in 5-fluorouracil
      treatment. Recently, the DNA polymorphism of this gene has been found to affect
      TS protein (pTS) expression. However, no prospective studies have been performed
      to evaluate the influence of this polymorphism on the clinical efficacy of 5-FU
      based adjuvant chemotherapy for colorectal cancer (CRC). In this study, we
      investigated the genotype of TS and immunopathological findings of pTS in 161
      colon cancer specimens from patients who were registered in a prospective
      adjuvant immunochemotherapy clinical trial. The clinical course and prognosis of
      these patients were checked after the study had been completed. This study
      comprised 11 (6.8%) cases of 2R/2R, 40 (24.8%) of 2R/3R, and 110 (68.3%) of 3R/3R
      genotypes. All of the 2R/2R cases were still alive at the time of analysis
      although this finding was not statistically significant. In this prospective
      examination on a randomized controlled trial, the patients with colon cancer of
      the 2R/2R TS genotype may be good responders to 5-FU-based adjuvant chemotherapy.
      Furthermore, differences in the proportions of the TS genotypes can account for
      the interracial differences in the adverse effects of 5-FU-based chemotherapy.

PMID- 17016602
TI  - A pilot study of metronomic temozolomide treatment in patients with recurrent
      temozolomide-refractory glioblastoma.
AB  - Frequent regular administration of chemotherapeutic agents at low doses, known as
      'metronomic chemotherapy', can increase the anti-angiogenic activity of the
      drugs, as has been confirmed by several other experimental tumor models. The aim
      of this pilot study was to evaluate the efficacy and safety of metronomic
      temozolomide (TMZ) treatment in twelve consecutive patients with recurrent TMZ
      refractory glioblastoma. The patients were administered by metronomic treatment
      schedule (continuous low-dose chemotherapy) with TMZ at a daily dose of 40
      mg/m(2). The median overall survival (OS) and progression-free survival (PFS)
      from the start of metronomic treatment were 11.0 months (95% CI, 5.2-10.5 months)
      and 6.0 months (95% CI, 0-12.3 months), respectively. During the follow-up
      period, complete response (CR) was not achieved in any patient, partial response
      (PR) in 2, and stable disease (SD) in 5 patients. Estimated PFS (CR+PR+SD) was
      58.3% at 3 months. Grade III/IV toxicity according to the National Cancer
      Institute Common Toxicity Criteria (NCI CTC) was not found. These results suggest
      that the change of chemotherapeutic schedule from conventional to metronomic
      treatment overcomes the chemo-resistance in patients with recurrent TMZ
      refractory glio-blastoma without any major toxicity.

PMID- 17016603
TI  - Variability in the diagnosis of dysplasia in ulcerative colitis by dynamic
      telepathology.
AB  - Telepathology (TP) is the practice of evaluating pathology cases by the digital
      transmission of diagnostic slides as either static pictures (static TP) or by a
      continuous flow of pictures from a robotic microscopy (dynamic TP). The
      diagnostic efficacy of dynamic TP-based consultation services has not been widely
      tested. Dysplasia arising in association with chronic ulcerative colitis (CUC)
      is, at present, the most important marker for an increased risk of malignancy in
      patients with this disease. However, the diagnosis of dysplasia suffers from a
      significant degree of intra- and interobserver variability which usually
      necessitates a second opinion prior to definitive treatment. Thus, it is often
      necessary to obtain expert consultation of potential dysplasia cases by dedicated
      gastrointestinal pathologists. The aim of this study was to evaluate the utility
      and interobserver variability of diagnosing dysplasia in CUC with the use of
      dynamic TP. Dynamic TP was used to evaluate digitalized images of 38 CUC cases
      with areas considered negative, indefinite, or positive for dysplasia (low or
      high grade) independently by seven pathologists. Subsequently, all cases were
      graded by each of the pathologists by light microscopic examination of the H&E
      stained glass slides. The degree of intra- and interobserver variability was
      determined by Kappa statistics. Overall, there was a poor degree of interobserver
      agreement (K=0.32) among the seven pathologists after analysis of the cases by
      dynamic TP. The poorest level of agreement was in the indefinite and low-grade
      dysplasia categories, whereas the highest level was in the negative and high
      grade dysplasia categories. Grouping together several diagnostic categories (for
      instance: Indefinite and low, or low- and high-grade dysplasia) had no
      significant effect on the level of agreement. The degree of variability in
      interpretation of cases by microscopic slide analysis was similar (K=0.35). After
      reviewing all the cases by microscopic analysis of the glass slides, the
      diagnosis was changed in 51% of the observations; in the majority of these (61%),
      the grade of dysplasia was decreased. In summary, the use of dynamic TP for
      consultation in CUC-associated dysplasia has a poor level of interobserver
      agreement, but does not differ significantly from that obtained by the evaluation
      of the cases by microscopic slide analysis. Diagnoses rendered by dynamic TP tend
      to be of a higher grade compared to that obtained by microscopic slide analysis.
      Thus, although dynamic TP may be used for the consultation of CUC dysplasia
      cases, more specific criteria are needed in the general categorization of
      dysplasia in CUC.

PMID- 17016604
TI  - p38MAPK inhibitor SB203580 sensitizes human SNU-C4 colon cancer cells to
      exisulind-induced apoptosis.
AB  - Sulindac sulfone (exisulind), is a promising anticancer agent because of its
      ability to induce apoptosis in a variety of malignant cell types and its minimal
      toxicity to normal cells. The induction of apoptosis is thought to account for
      the growth inhibitory effect of exisulind. The mitogen-activated protein kinase
      (MAPK) cascade has been implicated in the regulation of apoptosis in response to
      exisulind. With human SNU-C4 colon cancer cells that were much more resistant to
      exisulind than other colon cancer cells, in this study, we investigated whether
      the modulation of MAPK activity by using selective MAPK inhibitors can contribute
      to sensitizing SNU-C4 cells to exisulind. Exisulind (400 and 600 microM) slightly
      increased the phosphorylation of pERK1/2 but pretreatment with the pERK1/2
      inhibitor PD98059 did not significantly change the apoptotic response of SNU-C4
      cells. The same doses of exisulind increased the phosphorylation of p38MAPK, and
      pretreatment with the p38MAPK inhibitor SB203580 significantly potentiated growth
      inhibition and apoptosis induced by exisulind in SNU-C4 cells. We further found
      that apoptosis induced by a combination of exisulind and SB203580 was mediated
      through caspase activation. Collectively, our findings indicate that selective
      p38MAPK inhibitors potentiate apoptosis induction by exisulind in SNU-C4 cells.
      Such combinations may provide a more effective and less toxic strategy for the
      prevention or treatment of colon cancer.

PMID- 17016605
TI  - Different molecular pathways determining extrahepatic and intrahepatic
      recurrences of hepatocellular carcinoma.
AB  - Recent genome-wide screens have identified genes associated with the metastatic
      potential of hepatocellular carcinoma (HCC); however, there is little overlap
      between the identified genes, and interpretations of the results remain
      controversial. These inconsistencies may be related to differences in the sample
      populations, use of distinct microarray platforms and algorithms, and the
      complicated modes of HCC recurrence. We investigated the gene expression profiles
      of extrahepatic recurrence (EHR) and early intrahepatic recurrence (IHR), which
      are two representative modes of recurrence of HCC attributable to metastasis. We
      used DNA microarray analysis and identified 46 signature genes for EHR in 35 HCCs
      in a supervised learning manner. The obtained gene expression profile was
      compared with that for early IHR that was determined previously in the same
      manner. The 46 signature genes for EHR included many cell adhesion-related genes
      (ITGA6, SPP1, DNMBP, CD44 and POSTN), which all showed higher expression in HCC
      with EHR than in HCC without EHR. The 46 signature genes for early IHR included
      10 immune response-related genes, which all showed lower expression in HCC with
      early IHR than in HCC without early IHR. The signature genes for EHR included
      only two immune response-related genes (P=0.013). These results suggest that
      alteration of the cell adhesion system plays a central role in EHR and that
      reduction of the immune response is a specific step in early IHR. These results
      indicate that the metastatic processes in EHR and early IHR involve different
      molecular pathways.

PMID- 17016606
TI  - Rapid immunohistochemical detection of tumor cells in gastric carcinoma.
AB  - The detection of single tumor cells or tumor cell clusters represents an
      important issue in intraoperative frozen section analysis. For example, surgical
      margins may be evaluated in order to minimize the number of additional
      operations. Furthermore, intraoperative diagnosis of lymph node micrometastasis
      (LNM) may help to define the area of appropriate lymph node dissection. In
      addition to haematoxylin and eosin (H&E)-stained sections, immunohistochemical
      detection of single tumor cells or cell clusters may be helpful in this context.
      The aim of this study was to evaluate the clinical significance, reliability and
      sensitivity of intraoperative rapid immunostaining of frozen sections. Therefore,
      we compared the results of rapid immunohistochemical staining of frozen sections
      and paraffin sections applying the EnVision and Histofine(R) detection systems.
      In a prospective immunohistochemical study, paraffin and frozen sections of 20
      gastric cancer specimens were analyzed. Paraffin as well as frozen sections were
      stained immunohistochemically applying the EnVision and Histofine detection
      systems. As primary antibodies, AE1/AE3 (anti-cytokeratin), EMA (anti-MUC1) and B
      lymphocyte marker anti-CD20 were applied. The rapid immunostaining procedure was
      able to be completed within 10-13 min. Rapid immunohistochemical staining of
      frozen and paraffin sections of the same tumors resulted in comparable
      immunoreactivity. The rapid EnVision and Histofine procedures allowed
      immunostaining of frozen sections in less than 13 min. These methods can
      represent useful additional tools in routine surgical pathology and research,
      enabling a more accurate frozen section diagnosis compared to staining with H&E
      alone. Intraoperative rapid immunostaining can be a simple and useful technique
      to detect LNM.

PMID- 17016607
TI  - Connexin 32 expression reduces malignant phenotype in human A549 adenocarcinoma
      cells: Implication of Src involvement.
AB  - Recent evidence suggests that a member of the gap junction protein family,
      connexin (Cx) 32, acts as a tumor suppressor gene against lung adenocarcinoma.
      However, the precise mechanism remains unclear. In this study, we tried to
      explore the mechanism for the Cx32-dependent tumor-suppressive effect in lung
      adenocarcinoma. To perform this study, we established a stable clone of the human
      lung adenocarcinoma cell line, A549 in which the Cx32 gene was expressed. Cx32
      expression in A549 cells reduced anchorage-independent growth and development of
      tumors in a xenograft model. Additionally, Cx32 induced contact inhibition of
      growth and reduced invasive activity in A549 cells. The tumor-suppressive effects
      of Cx32 depended on the inhibition of Src activity. These events were confirmed
      by an Src inhibitor (PP1) and siRNA for Cx32. These results suggest that the Cx32
      dependent tumor-suppressive effect in A549 cells is explained by the inhibition
      of Src activity.

PMID- 17016608
TI  - Williams-Beuren syndrome: determination of deletion size using quantitative real
      time PCR.
AB  - Williams-Beuren syndrome (WBS) is a rare genetic disorder (1/20,000-50,000) and
      is usually caused by a 1.5- to 1.8-Mb heterozygous deletion on chromosome
      7q11.23. At least 25 genes have been identified in the deletion region in WBS
      patients, which is flanked by large low-copy-repeat sequences (> 320 kb). By
      using FISH as well as microsatellite analysis, it is not possible to get a
      precise identification of the size of the deletion. For determining the deletion
      size, we developed a reliable quantitative PCR approach. Our assay screens 2.5 Mb
      of the WBS region in 100- to 300-kb intervals. This methodology has been tested
      in DNA samples of 65 patients with the clinical suspicion of WBS. In every case
      we were able to exclude or to identify the presence of a deletion and to
      determine its size. Deletion size varied from 0.2 Mb to 2.5 Mb. The 2.5-Mb
      rearrangement represents the largest deletion described at present and it was
      detected in a severely affected patient. We report the detection efficiency of
      this new system and the genotype/phenotype correlation.

PMID- 17016609
TI  - Local in vivo administration of a decoy oligonucleotide targeting NF-kappaB
      induces apoptosis of osteoclasts after application of orthodontic forces to rat
      teeth.
AB  - In this study, we report the in vivo effects of a decoy oligonucleotide targeting
      the nuclear factor kappaB (NF-kappaB) on osteoclasts during forced orthodontic
      tooth movement in rats. Wistar rats were subjected to orthodontic forces, in the
      absence or presence of treatment with a decoy molecule mimicking a nonsymmetric
      NF-kappaB binding site (5'-CGC TGG GGA CTT TCC ACG G-3'). TUNEL staining of
      fragmented DNA revealed that treatment with NF-kappaB decoy but not with scramble
      double-stranded oligodeoxynucleotides (ODN) induced a high level of osteoclast
      apoptosis in vivo. Immunohystochemical analysis for death receptor Fas revealed
      strong positivity only in samples treated with NF-kappaB decoys, demonstrating
      that osteoclasts are sensitive to death induction via Fas signaling. Induction of
      apoptosis in osteoclasts could be a strategy for treatment of excessive
      osteoclast activity in pathologic conditions such as osteoporosis, peri-articular
      osteolysis, inflammatory arthritis, Paget's syndrome and tumour-associated
      osteolytic metastases.

PMID- 17016610
TI  - Endothelial cells from human cerebral aneurysm and arteriovenous malformation
      release ET-1 in response to vessel rupture.
AB  - Cerebral aneurysms and arteriovenous malformations (AVM) are a common cause of
      stroke and cerebral hemorrage. Both are often discovered when they rupture,
      causing subarachnoid hemorrhage (SAH). SAH-induced vasospasm is mediated by
      enhanced vasoconstriction due to endothelin-1 (ET-1). We investigated whether
      endothelial cells (ECs) obtained from aneurysm and AVM express phenotypic and
      genotypic alterations contributing to the development of vasospasm after SAH. We
      isolated ECs from human AVM and aneurysm and then confirmed their EC origin by
      polymerase chain reaction and immunocytochemistry with endothelial markers.
      Experiments were also carried out with human cerebral microvascular and umbilical
      vein ECs (HCECs and HUVECs respectively) for comparison. We tested EC
      proliferation ability and microtubule formation in Matrigel at different cell
      passages. Five aneurysm (3 ruptured, 2 unruptured) and 3 AVM (2 ruptured, 1
      unruptured) ECs were tested for ET-1 release in the culture medium. Aneurysm and
      AVM ECs expressed von Willebrand factor, Adrenomedullin, and exhibited a
      progressive reduction of proliferation and in vitro angiogenic ability after the
      V passage. Significantly higher levels of ET-1 have been detected in ECs from
      ruptured aneurysms and AVMs. We report the first successful isolation and
      characterization of primary EC lines from human cerebral vascular lesions.
      Augmented release of ET-1 is correlated with the rupture of the abnormal vessel
      confirming its role in vasospasm after SAH. Furthermore, ECs obtained from these
      vascular malformations can be used as an experimental model to study SAH-induced
      vasoconstriction.

PMID- 17016611
TI  - Inflammatory response of esophageal epithelium in combined-type esophagitis in
      rats: a transcriptome analysis.
AB  - Recent studies have shown that esophageal mucosal inflammatory response is
      involved in the pathophysiology of gastro-esophageal reflux disease. The aim of
      the present study was to identify specific gene expression profiles of the
      esophageal mucosa in a rat model of combined-type chronic reflux esophagitis.
      Esophagogastroduodenal anastomosis was carried out in male Wistar rats by
      anastomosing the jejunum to the gastroesophageal junction under diethyl-ether
      inhalation anesthesia. Esophageal epithelial cells were obtained from esophagi of
      rats by laser capture microdissection. Preparation of cRNA and target
      hybridization were performed according to the Affymetrix GeneChip eukaryotic
      small sample target labeling assay protocol. The gene expression profile was
      evaluated by the rat toxicology U34 GeneChip. Array data analysis was carried out
      using Affymetrix GeneChip operating software, ingenuity pathway analysis
      software, and Gene Springs software. A comparison between esophagitis and sham
      operated rats 2 weeks after the operation revealed that 368 probes (36%) were
      significantly affected, i.e. 185 probes were up-regulated, and 183 probes were
      down-regulated, both at levels of at least 1.5-fold in the esophagitis rats.
      Ingenuity signal analysis of 207 affected probes revealed the interleukin-6
      signaling pathway as the most significantly affected caronical pathway. In
      addition, the expression of many genes associated with cytokine and transcription
      factor was enhanced in the esophagitis rats. This transcriptome approach provided
      insight into genes and putative genetic pathways thought to be affected by
      stimulation with gastroduodenal refluxates.

PMID- 17016612
TI  - Natural killer T cells ameliorate antibody-induced arthritis in macrophage
      migration inhibitory factor transgenic mice.
AB  - Macrophage migration inhibitory factor (MIF) plays an important role in
      inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene
      disruption ameliorate joint inflammation in a mouse model of arthritis induced by
      anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC
      mAb/LPS). In the present study, using the anti-IIC mAb/LPS system, we have
      analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We
      found that MIFTg mice developed more severe arthritis than WT mice. The
      histopathological scores were significantly higher in MIFTg mice and
      significantly increased numbers of CD69+ T cells were detected in the spleens of
      these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells
      from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon
      stimulation with agr;-galactosylceramide (alpha-GalCer). Further, repeated
      administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of
      both clinical and histopathological scores of arthritis, with a significant
      decrease in IL-6. The present findings demonstrate that overexpression of MIF
      exacerbates inflammation in this arthritis model and that NKT cells play an
      ameliorating role upon stimulation with alpha-GalCer in the inflammatory process
      in MIFTg mice.

PMID- 17016613
TI  - Metabolic activity of rat hepatocytes cultured on homologous acellular matrix and
      transplanted into Gunn rats.
AB  - The metabolic activity of hepatocytes cultured on homologous acellular matrix
      (HAM) and transplanted into rats genetically incapable of bilirubin conjugation
      (Gunn rats) has been investigated. Hepatocytes from Wistar male rats were seeded
      on HAM and cultured for 9 days, and the proliferation rate and albumin mRNA
      expression were assayed daily. HAM alone or HAM plus hepatocytes (cultured for 3
      days) were implanted in a subcutaneous pocket of the dorsal region of Gunn rats.
      No immunosuppression therapy was used. Blood samples were collected weekly and
      rats were sacrificed 10 weeks after surgery. Hepatocytes cultured on HAM
      displayed a higher proliferation rate than those cultured on plastic, and albumin
      mRNA expression was detected in hepatocytes seeded on HAM, but not on plastic.
      Serum bilirubin concentrations did not differ from baseline values in both the
      sham-operated control and HAM transplanted rats. On the contrary, in rats
      transplanted with HAM plus hepatocytes, circulating bilirubin levels decreased
      from week 4-7, and then plateaued until week 10. Histology did not evidence signs
      of rejection, but only a mild degree of inflammation around the implanted
      patches. It is concluded that hepatocytes seeded on HAM and transplanted into
      Gunn rats are able to metabolize bilirubin for at least two months, without signs
      of rejection even in the absence of immunosuppressive therapy.

PMID- 17016614
TI  - Genetic factors for obesity.
AB  - The purpose of the present study was to identify gene polymorphisms for the
      reliable assessment of genetic factors for obesity. The study population
      comprised 3906 unrelated Japanese individuals (2286 men, 1620 women), including
      1196 subjects (677 men, 519 women) with obesity (body mass index of > or = 25
      kg/m2) and 2710 controls (1609 men, 1101 women). The genotypes for 147
      polymorphisms of 124 candidate genes were determined with a method that combines
      the polymerase chain reaction and sequence-specific oligonucleotide probes with
      suspension array technology. Multivariable logistic regression analysis with
      adjustment for age, sex, and the prevalence of smoking revealed that the 
      30Gright curved arrow A polymorphism of GCK, the -240Aright curved arrow T
      polymorphism of ACE, and the -482Cright curved arrow T polymorphism of APOC3 were
      significantly (P < 0.01) associated with the prevalence of obesity, and the 
      1989Tright curved arrow G polymorphism of ESR1 was almost significantly
      associated. A stepwise forward selection procedure demonstrated that ACE, GCK,
      and ESR1 genotypes significantly (P < 0.01) and independently affected the
      prevalence of obesity. Combined genotype analysis for these three polymorphisms
      yielded a lowest odds ratio of 0.45 for the combined genotypes of AT or TT for
      ACE, GG for GCK, and GG for ESR1 in comparison with the combined genotypes of AA
      for ACE, GG for GCK, and TT or TG for ESR1. Genotypes for ACE, GCK, and ESR1 may
      prove reliable for the assessment of genetic factors for obesity. Determination
      of the combined genotypes for these genes may contribute to the personalized
      prevention of this condition.

PMID- 17016615
TI  - The mismatch repair gene hPMS2 is mutated in primary breast cancer.
AB  - Mismatch repair (MMR) genes play a fundamental role in the correction of
      replication errors and their mutation leads to cancer development. In the present
      study we have analyzed the hPMS2 MMR gene for mutation using 20 primary breast
      cancers and seven breast tissues obtained from areas adjacent to breast cancer.
      For this purpose we have used cDNA sequence analysis and Western blotting using
      the specific antibody against the amino-terminal domain E-19. In primary breast
      cancers we found that the hPMS2 gene had 9 missense mutations [codons: 513 (by
      change of Ser x Asp) in 14 tumors, 520 (Ala x Val) in 8 tumors, 573 (by change of
      Thr x Ser in 19 tumors), 578 (by change of Arg x Leu in 9 tumors), 587 (by change
      of Ser x Asp in 7 tumors), 590 (by change of Ile x Leu in 12 tumors), 598 (by
      change of Gln x His in 5 tumors), 601 (by change of Ser x Leu in 13 tumors), 608
      (by change of Ala x Ser in 9 tumors. Nine out of 20 breast cancers had a non
      sense mutation in nucleotide 1862 by changing Adenine by Thymine (AAG x TAG),
      which corresponded with a change in codon 613 by a change of Lys by stop codon.
      This non-sense mutation is responsible for the premature truncation of the
      protein hPMS2, which is reflected in the Western blotting by two bands, one
      corresponding with the wild-type form (100 kDa) and a lower one (75 kDa)
      corresponding with the truncated form of the hPMS2 MMR protein. This truncated
      protein and the mutations in the hPMS2 gene were also detected in two samples of
      normal-appearing tissue adjacent to their corresponding cancerous lesion.
      Altogether the present report demonstrates that primary breast cancers harbor
      mutations in this MMR gene and that normal-appearing breast tissue adjacent to
      the primary lesion also harbors the same mutations before the neoplastic process
      is manifested.

PMID- 17016616
TI  - Ex vivo HR-MAS MRS of human meningiomas: a comparison with in vivo 1H MR spectra.
AB  - We report on the magnetic resonance spectroscopy (MRS) characterisation of
      different human meningiomas. Three histological subtypes of meningiomas
      (meningothelial, fibrous and oncocytic) were analysed both through in vivo and ex
      vivo MRS experiments. The ex vivo high-resolution magic angle spinning (HR-MAS)
      investigations, permitting an accurate description of the metabolic profile, are
      very helpful for the assignment of the resonances in vivo of human meningiomas
      and for the validation of the quantification procedure of in vivo MR spectra. By
      using one- and two-dimensional experiments, we were able to identify several
      metabolites in different histological subtypes of meningiomas. Our spectroscopic
      data confirmed the presence of the typical metabolites of these benign neoplasms
      and, at the same time, that meningomas with different morphological
      characteristics have different metabolic profiles, particularly regarding
      macromolecules and lipids. The ex vivo spectra allowed a better understanding and
      interpretation of the in vivo MR spectra, showing that the HR-MAS MRS technique
      could be a complementary method to strongly support the in vivo MR spectroscopy
      and increase its clinical potentiality.

PMID- 17016617
TI  - Genetic risk for atherothrombotic cerebral infarction in individuals stratified
      by sex or conventional risk factors for atherosclerosis.
AB  - The aim of the present study was to assess the genetic risk for atherothrombotic
      cerebral infarction (ACI) in men and women separately as well as in individuals
      with or without conventional risk factors for atherosclerosis and thereby to
      contribute to the personalized prevention of ACI. The study population comprised
      2705 unrelated Japanese individuals (1244 men, 1461 women), including 636
      subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had
      or did not have conventional risk factors for atherosclerosis, including
      hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202
      polymorphisms of 152 candidate genes were determined by a method that combines
      polymerase chain reaction and sequence-specific oligonucleotide probes with
      suspension array technology. Multivariable logistic regression analysis and a
      stepwise forward selection procedure revealed that 11 different polymorphisms
      were significantly (P < 0.005) associated with ACI in women or men or in
      individuals with or without hyper-tension, hypercholesterolemia, or diabetes
      mellitus: the 584C-->T polymorphism of LIPG, 5665G-->T of EDN1, and G-->A of
      CCL11 in women; 677C-->T of MTHFR, 1323C-->T of ITGB2, 3932T-->C of APOE, and 
      231A-->G of EDNRA in men; -572 G -->C of IL6 in hypertensive individuals; -403G-
      >A of CCL5 and G-->A of COMT in individuals with hypercholesterolemia; and 3932T-
      > C of APOE and A-->G of TNFSF4 in diabetic individuals. Polymorphisms associated
      with ACI may thus differ between women and men as well as among individuals with
      different risk factors. Stratification of subjects on the basis of sex or
      conventional risk factors for atherosclerosis may therefore be important in order
      to achieve the personalized prevention of ACI with the use of genetic
      information.

PMID- 17016618
TI  - Dual regulation of soluble tumor necrosis factor-alpha induced activation of
      human monocytic cells via modulating transmembrane TNF-alpha-mediated 'reverse
      signaling'.
AB  - Transmembrane tumor necrosis factor-alpha (mTNF-alpha) is known to be the
      precursor of soluble TNF-alpha (sTNF-alpha). mTNF-alpha can act as a ligand on
      the TNF receptor- (TNFR)- bearing cell through 'forward signaling' or as a
      receptor on the TNF producing cell through 'reverse signaling'. In the current
      study, we investigated the role of mTNF-alpha-mediated reverse signaling in
      regulating sTNF-alpha-induced activation of human monocytic U937 cells. We
      demonstrated that pretreatment with sTNFRI, for inducing reverse signaling
      through mTNF-alpha, sensitized U937 cells to sTNF-alpha stimulation, as evidenced
      by an increase in reactive oxygen production and mRNA levels of proinflammatory
      cytokines (TNF-alpha, IL-1beta, and IL-8) in these cells. Further experiments
      revealed that IkappaB-alpha degradation was increased in the monocytic cells
      primed with sTNFRI, implying that reverse signaling of mTNF-alpha sensitizes U937
      cells via an NF-kappaB-dependent mechanism. On the other hand, binding of sTNFRI
      to mTNF-alpha after sTNF-alpha-induced activation of U937 cells reduced mRNA
      stability (half-life) of IL-1beta and IL-8. The involvement of reverse signaling
      in the process was verified by using a mutated form of mTNF-alpha lacking the
      majority of the cytoplasmic domain. Our results clearly showed that enhanced mRNA
      degradation of the cytokines occurred only in U937 cells transfected with a wild
      type mTNF-alpha, but not in those cells transfected with the mutant mTNF-alpha.
      Taken together, these data suggest that reverse signaling through mTNF-alpha may
      exert a double role in modulating sTNF-alpha bioactivity. It is positive when
      reverse signaling occurs prior to sTNF-alpha stimulation, while it is negative
      when reverse signaling occurs after the sTNF-alpha signal. Thus, our findings
      strengthen a role of mTNF-alpha-mediated reverse signaling in the regulation of
      immune-inflammatory response and control of inflammatory reaction.

PMID- 17016619
TI  - Suppressive effect of non-anaphylactogenic anti-IgE antibody on the development
      of dextran sulfate sodium-induced colitis.
AB  - Inflammatory bowel disease (IBD) is a spectrum of immune-mediated chronic
      disorders of the intestine. Patients with IBD tend to exhibit significantly
      elevated levels of IgE in their serum. In general, the pathogenesis of IBD
      exhibits inflammatory events such as immunoglobulin E (IgE)-mediated
      hypersensitivity. We examined the effect of the non-anaphylactogenic anti-IgE
      antibody, which has been known to block IgE functions, in an animal model of
      ulcerative colitis induced by the oral intake of dextran sulfate sodium (DSS) for
      seven days. The non-anaphylactogenic anti-IgE antibody was subcutaneously
      injected on day 0 of DSS treatment. The disease activity index (DAI) was
      calculated by scoring intestinal states, including body weight loss, diarrhea,
      and rectal bleeding, and the activities of myeloperoxidase (MPO) and chymase were
      measured in the colon tissue. In addition, the expression of tumor necrosis
      factor (TNF)-alpha and cyclooxygenase (COX)-2 was determined by Western blotting.
      Administration of the anti-IgE antibody markedly reduced the histological damage
      to the colon and the DAI increment exhibited by the DSS-induced colitis. The anti
      IgE antibody also significantly suppressed the activities of MPO and chymase as
      well as the expression of TNF-alpha and COX-2 in the DSS-treated colon tissue.
      Furthermore, the elevation of IgE levels in serum was induced by DSS and reduced
      by anti-IgE antibody injection. Thus, these results indicate that the IgE
      response played an important role in the clinical signs and the expression of
      inflammatory mediators in a colitis model caused by DSS treatment, suggesting
      that the non-anaphylactogenic anti-IgE antibody may be a useful therapeutic agent
      for ulcerative colitis.

PMID- 17016620
TI  - Transcriptional targeting of virus-mediated gene transfer by the human hexokinase
      II promoter.
AB  - The efficacy of the most commonly used form of suicide gene therapy, the HSV
      TK/GCV method, utilizing herpes simplex virus thymidine kinase (HSV-TK) and
      antiviral drug ganciclovir (GCV) has been demonstrated in clinical trials.
      However, safer delivery of the therapeutic gene and more controlled regulation of
      the transgene expression, the essential prerequisites for successful therapeutic
      use, are still needed. We describe improved suicide gene therapy against cancer
      through transcripitional targeting by a strong and selective tumor-specific human
      hexokinase II promoter (hHKII). We examined the targeting properties of the human
      hHKII promoter in different human non-small cell lung cancer (NSCLC) and other
      human cancer cell lines using self-inactivating, VSV-G pseudotyped lentiviral
      vector. To confirm accurate transcriptional targeting of the hHKII promoter, the
      lack of transgene expression was verified in human primary bronchial epithelial
      and bronchial fibroblast cells. Furthermore, tissue-specific expression of the
      promoter was confirmed using transgenic mouse lines carrying the hHKII promoter
      driven luciferase reporter gene. We also tested the efficacy of the HSV-TK/GCV
      suicide gene therapy with the hHKII targeted lentiviral vector to NSCLC cells.
      Our results show that the hHKII promoter is strongly expressed in cancer cells.
      The targeted vector with the shortest hHKII promoter fragment (352 bp) appeared
      to have the best targeting properties because it efficiently governed the
      expression of the therapeutic gene in cancer cell lines, especially in certain
      non-small cell lung cancer cell lines, the transgene expression in human primary
      cells was virtually undetectable, and expression of the proximal hHKII promoter
      in transgenic mice was very low in most tissues. Also, the anti-cancer efficacy
      of HSV-TK/GCV therapy with the hHKII-targeted vector was comparable to that
      obtained with the control vector that utilized a commonly used constitutive
      promoter from the human elongation factor 1 alpha (hEF1alpha) gene. In
      conclusion, the transcriptionally targeted lentivirus vector with hHKII promoter
      can successfully direct HSV-TK/GCV suicide gene therapy to non-small cell lung
      cancer and other tumor cell types. These results warrant further studies with
      orthotopic animal tumor models and primary human cancer material.

PMID- 17016621
TI  - Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and
      amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis
      and necrosis induction.
AB  - The effects of amrubicin (AMR) and its active metabolite, amrubicinol (AMROH), on
      the sensitivity of human lung adenocarcinoma A549 cells to ionizing radiation
      were investigated in vitro. Further, the kinetics of apoptosis and necrosis
      induction were also analyzed. The cytocidal effects of X-ray irradiation on A549
      cells resulted in a low level of radiosensitivity with a D0 value of 12 Gy. The
      slopes of the survival curves in the exponential phase were plotted on
      semilogarithmic paper for radiation combined with AMR (2.5 microg/ml) and AMROH
      (0.02 microg/ml) treatment, and were shown to be approximately parallel to
      treatment with irradiation alone. The initial shoulder-shape portion of the
      survival curve for radiation alone, indicating the repair of sublethal damage,
      was reduced as compared to that for sequential combined treatment with AMR or
      AMROH. Sequential treatments with AMR or AMROH prior to ionizing radiation
      resulted in an additive radio-enhancement effect that reduced not only survival,
      but also the shoulder width. Fractionated irradiation with 2 Gy per fraction of
      A549 cells was carried out in vitro similar to that commonly performed in
      clinical radiotherapy and the radio-resistance of the cells was shown to be
      inhibited by AMR and AMROH. Similar to AMR and AMROH, adriamycin and etoposide
      (VP-16) are DNA topoisomerase II inhibitors. The effects of these 4 agents on
      cells that received X-ray irradiation were compared and all of the agents
      exhibited comparable radio-enhancement effects. The induction of apoptosis was
      investigated at 48 and 72 h after administration of AMROH, radiation or combined
      treatment, and apoptosis was not significantly induced after any of the
      treatments. We also examined the induction of necrosis, and found that the
      incidence of necrosis following combined treatment was approximately 2 times
      higher than that with either of the single treatments.

PMID- 17016622
TI  - Multiple splicing variants of Naf1/ABIN-1 transcripts and their alterations in
      hematopoietic tumors.
AB  - Naf1 (Nef-associated factor 1)/TNIP1/ABIN-1 (A20-binding inhibitor of NF-kappaB
      activation) is a cellular protein that interacts and cooperates with the NFkappaB
      inhibiting protein A20. It is reported that Naf1 attenuates epidermal growth
      factor (EGF)/extracellular-signal-regulated kinase2 (ERK2) nuclear signaling.
      Naf1 also binds to Nef, which plays a key role in acquired immunodeficiency
      syndrome pathogenesis and HIV-1 virus replication. Naf1 mRNA consists of 18 exons
      and multiple splice variants have been reported; two isoforms for exon 1,
      deletion of exon 2 and isoforms alpha and beta for exon 18. Using specimens from
      29 acute myeloid leukemia (AML) patients, we detected a high frequency of allelic
      loss on DNA at STS marker D5S2014 near the Naf1 gene. We therefore performed
      mutation and expression analyses using leukemia-lymphoma lines and 6 pairs of
      clinical AML samples. There was no mutation in the Naf1 coding region of any
      sample. As a result of expression analysis, we identified novel splice variants
      of the Naf1 gene; deletion of exon 16 (Naf1 alpha2, Naf1 beta2), deletion of exon
      16 with an insertion (Naf1 alpha3, Naf1 beta3) and deletion of exons 16 and 17
      (Naf1 alpha4). Naf1 alpha3 and beta3 showed premature termination. In peripheral
      blood mononucleocytes (PBMNCs) from healthy adults, almost no expression of full
      length Naf1 (Naf1FL), Naf1 alpha3 and beta3 were observed. In contrast, their
      expression was clear in AML blasts and in the majority of leukemia-lymphoma lines
      investigated. Naf1 alpha2 was widely expressed in PBMNCs from healthy adults, AML
      blasts and cell lines, suggesting it is the main transcript of the Naf1 gene.
      Luciferase assay revealed that Naf1 alpha2 had equal NF-kappaB inhibitory effect
      to that of Naf1FL, while Naf1 alpha4 was less effective. In clinical AML
      patients, the expression of Naf1 alpha3 was much higher at diagnosis than on
      remission after chemotherapy, suggesting the possible dominant negative effect of
      Naf1 alpha3.

PMID- 17016623
TI  - Functional characterization of histamine receptor subtypes in a human bronchial
      epithelial cell line.
AB  - Histamine is a well-known mediator eliciting a broad range of responses in
      different cell types. Four different subtypes of G protein-coupled histamine
      receptors (H1-H4) have been cloned and pharmacologically characterized. However,
      involvement of the different histamine receptor subtypes in immunomodulatory
      functions of bronchial epithelium has only been investigated marginally. The
      expression and function of histamine receptor subtypes on the human bronchial
      epithelial cell line BEAS-2B was analyzed by PCR, intracellular Ca++ 
      measurements and ELISA. We show mRNA expression of the histamine receptor
      subtypes H1, H2, and H3, but not H4 in the human bronchial epithelial cell line
      BEAS-2B. Using intracellular Ca++ -measurements, we demonstrated functional
      expression of the H1 and H3 receptors. To characterize the biological properties
      of histamine in airway epithelial biology, we also investigated its effects on
      cytokine secretion by BEAS-2B cells. Thereby, we were able to show up-regulation
      of the proinflammatory mediators IL-6 and CXCL8/ IL-8 via activation of the H1,
      H2 and H3 receptor subtypes. The Th1 cytokines CXCL9/MIG and CXCL10/IP-10 and the
      chemokine CCL5/RANTES were regulated in a distinct manner: Whereas histamine
      inhibited the IFN-gamma/TNF-alpha-induced secretion of MIG via the histamine
      receptor subtypes H1, H2, and H3, the histamine-induced suppression of RANTES was
      due to activation of the H2 and H3 receptors, while reduction of cytokine
      triggered IP-10 secretion was mediated only by triggering the H2 receptor. In
      summary our data provide evidence that histamine released during allergic lung
      diseases exerts regulatory influence on airway epithelial cells.

PMID- 17016624
TI  - Association of phosphodiesterase 4D gene polymorphisms with chronic obstructive
      pulmonary disease: relationship to interleukin 13 gene polymorphism.
AB  - Activation of the cyclic AMP (cAMP) signaling pathway leads to the suppression of
      inflammation in the airways and relaxation of airway smooth muscle. Intracellular
      cAMP levels are determined by a balance between the activities of adenylate
      cyclase and phosphodiesterases. We hypothesized that polymorphisms of the
      phosphodiesterase 4D (PDE4D) gene activate its protein function which leads to
      the downregulation of cAMP, resulting in the development of chronic obstructive
      pulmonary disease (COPD). A case-control study was performed using Japanese (96
      COPD patients and 61 controls) and Egyptians (106 COPD patients and 72 controls)
      to investigate the association between the polymorphisms of the PDE4D gene and
      the development of COPD. Genotyping of all subjects for SNP7 (dbSNP ID,
      rs10075508), SNP13 (rs829259) and SNP15 (rs702531) in exon 15 of the PDE4D gene
      was conducted. Furthermore, the distributions of haplotypes consisting of PDE4D
      polymorphisms and those of interleukin (IL) 4, IL13 and beta2 adrenoceptor were
      analyzed. The distribution of SNP13 allele frequencies of the PDE4D gene was
      significantly different between the COPD and control groups in the Japanese
      population (p = 0.041). In haplotype analysis, haplotypes composed of PDE4D SNP7
      and IL13 +2044 G/A in the Japanese population showed significant difference
      between the patients and controls (pcorr = 0.00048). Thus, SNP13 and haplotypes,
      SNP7 G/A and IL13 +2044 G/A, may be useful for predicting COPD susceptibility.

PMID- 17016625
TI  - Tumour-stroma interactions between metastatic prostate cancer cells and
      fibroblasts.
AB  - Previous work has shown the importance of tumour-stroma interactions for prostate
      cancer development at the primary site. The aim of the present study was to find
      out whether evidence can be found for a tumour-stroma cross- talk also between
      metastatic prostate cancer cell lines and non-prostatic stromal fibroblasts which
      are encountered by metastatic cells at most sites. We addressed this issue in
      cell culture systems using 3 metastatic human prostate cancer cell lines (LnCaP,
      PC-3 and DU-145) on the one hand, and a human fibroblast line (HFF, human
      foreskin fibroblasts) on the other. We incubated fibroblasts with tumour cell-
      and tumour cells with fibroblast-conditioned media and evaluated several
      parameters important for the establishment of metastases such as cell
      proliferation, migration and expression of matrix degrading proteases. We also
      determined in the conditioned media the concentrations of several growth factors
      and cytokines which might be responsible for the observed effects. We found that
      media conditioned by all 3 metastatic prostate cancer cell lines stimulated
      fibroblast proliferation which corresponds to fibrous stroma induction in vivo.
      DU-145 cell conditioned media induced in fibroblasts expression of mmp-1 mRNA
      known to be important for tumour invasion. ELISA assays revealed that tumour
      cells secrete bFGF, PDGF and TNFalpha known to stimulate fibroblast proliferation
      and/or MMP-1 expression. Cultivation of DU-145 carcinoma cells in fibroblast
      conditioned medium resulted in an enhanced proliferation and anchorage
      independent growth of this cell line in soft agar. Fibroblast conditioned medium
      also increased migration of PC-3 cells in the wound assay and slightly augmented
      mmp-1 expression. KGF (able to stimulate proliferation of normal and neoplastic
      prostate epithelial cells) was secreted by fibroblasts at higher concentrations
      than by all 3 tumour cell lines. In addition, fibroblasts secreted TNFalpha,
      bFGF, PDGF, HGF and also VEGF, the most important factor for tumour
      vascularization. Our results provide evidence that tumour-stroma interactions do
      not only exist at the primary site but also between metastatic prostate cancer
      cell lines and their fibroblastic microenvironment. These interactions, which are
      mediated through secreted factors, affect several steps of the metastatic cascade
      including proliferation, anchorage-independent growth, migration and the
      secretion of matrix-degrading proteases.

PMID- 17016626
TI  - Neuromedin U receptor 1 expression in the rat endocrine pancreas and evidence
      suggesting neuromedin U suppressive effect on insulin secretion from isolated rat
      pancreatic islets.
AB  - Neuromedin U (NmU) is a regulatory peptide found in significant concentrations in
      both the brain and gut of the rat and is named according to its ability to
      powerfully contract the uterus. Two types of NmU receptors were recently
      identified and subsequent studies evidenced NmU involvement in the regulation of
      energy homeostasis. Such a role of neuromedin U suggests that a polypeptide may
      also be involved in the regulation of adipoinsular axis function. Therefore in
      the present study we examined the expression of NmU receptors in pancreatic
      islets using RT-PCR and Western blotting analysis. We also investigated the role
      of NmU in regulation of insulin secretion in vitro using isolated pancreatic
      islets. We have confirmed that NmUR1 but not NmUR2 is specifically expressed in
      isolated rat pancreatic islets. In all tested doses (1, 10, 100 nmol/l) NmU dose-
      dependently decreased insulin output by isolated pancreatic islets. These
      inhibitory effects of NmU on insulin secretion may suggest the involvement of NmU
      in regulating the pancreatic branch of adipoinsular axis function. Thus, NmU can
      be included in that group of anorectic peptides, which are also involved in the
      regulation of insulin secretion.

PMID- 17016627
TI  - The effects of macrophage migratory inhibitory factor on acute-phase protein
      production in primary human hepatocytes.
AB  - Macrophage inhibitory factor (MIF) is a pituitary peptide released during the
      physiological stress response, a T-cell product secreted during the antigen
      specific response and a pro-inflammatory macrophage cytokine secreted after LPS
      stimulation. It has become apparent that MIF is central to the regulation of the
      inflammatory response and is implicated in the pathogenesis of a variety of acute
      and chronic inflammatory conditions. This is, at least in part, due to the
      apparent counter-regulation of the anti-inflammatory actions of glucocorticoids,
      including the reversal of glucocorticoid-mediated IL-6 release inhibition. This
      study examines the effect of recombinant MIF on regulation of the acute phase
      response in isolated human hepatocytes. MIF alone increased C-reactive protein
      (CRP) release in a dose-dependent manner < or = 0.1 ng/ml after which the effects
      of MIF were attenuated. In combination with IL-6 both CRP and and alpha-1
      antichymotrypsin (ACT) release were increased above levels found with either IL-6
      or MIF treatment alone. Dexamethasone attenuated the effects of MIF upon CRP
      production but increased the MIF stimulated release of ACT. The study
      demonstrates that the effects of MIF upon the acute phase response are complex
      and can differentially modulate the production of acute phase proteins depending
      on the presence of other factors.

PMID- 17016628
TI  - Expression of the Nd1 gene is down-regulated by doxorubicin at post
      transcriptional level.
AB  - Doxorubicin is an anti-neoplastic agent with cardiotoxicity as a side effect. We
      previously demonstrated that doxorubicin treatment of mice resulted in a
      selective decrease in expression of the Nd1 gene, which encoded a new kelch
      family actin binding protein in the heart. Here we show that doxorubicin
      treatment also reduced the Nd1 expression in various organs of mice and cultured
      cell lines. The treatment of Nd1-transgenic mice and Nd1-transfectants also
      selectively reduced levels of the exogenous Nd1 mRNAs, whose expression was under
      the control of various promoters. Furthermore, the doxorubicin-induced reduction
      of Nd1 mRNA expression in NIH3T3 cells was inhibited by treatment of these cells
      with cycloheximide. Thus, the doxorubicin treatment may specifically reduce the
      stability of Nd1 mRNA.

PMID- 17016629
TI  - Hemostasis alterations in metabolic syndrome (review).
AB  - Metabolic syndrome (MS) is characterized by the presence of at least three of the
      following alterations: enlargement of the waist diameter, higher levels of
      arterial pressure, low density lipoprotein cholesterol and glycemia, and
      reduction of high density lipoprotein cholesterol. The prevalence of MS reaches
      23% in young adults, a percentage that increases with age. People with MS have a
      greater risk of suffering from cardiovascular disease (CVD). The physiopathologic
      alterations now found to exist in MS are diverse; among them is endothelial
      dysfunction, which triggers atherogenic lesions and hypercoagulability
      characterized by alterations of the coagulation factors and the regulatory
      proteins of fibrinolysis such as the plasminogen activator inhibitor (PAI-1). The
      increase in oxidative stress and/or the reactive oxygen species in patients with
      MS is partially related to the oxidation state of the lipoproteins, especially of
      the low density lipoproteins. This fact favors atherogenesis. Moreover, the
      oxidative stress produces alterations in the production of adipokines, cytokines
      secreted by the adipose tissues. The abnormality in the transport of lipoprotein
      diminishes the catabolism of the very low density lipoprotein (VLDL) and
      increases the catabolism of the high density lipoprotein (HDL), which creates
      insulin resistance. This process is associated with a lower concentration of
      adiponectin that in turn regulates the catabolism of VLDL and HDL; consequently
      increasing the flow of fatty acids from the adipose tissue to the liver and
      muscles. The proinflammatory cytokines, among them tumor necrosis factor alpha
      (TNF-alpha), are of great importance in MS regulating different processes and
      molecules such as PAI-1. PAI-1 is controlled by the group of transcription
      factors peroxisome proliferator-activated receptor (PPAR), especially by PPAR
      gamma and alpha ligands. In summary, MS includes multiple alterations related to
      insulin resistance at several levels: hepatic, muscular, adipose and vascular
      tissue (endothelium). The exact mechanism that underlies the relationship between
      MS and CVD are not sufficiently known yet; pathogenic explanations are lacking
      for the mechanisms relating metabolic factors to insulin resistance and the
      association with the development of atherosclerosis and thrombosis. MS
      alterations and the main aspects related to homeostasis alterations are examined
      in this report.

PMID- 17016630
TI  - Antiangiogenic activity of a concentrated effective microorganism fermentation
      extract.
AB  - We have previously demonstrated the possible growth inhibitory activity of both
      first generation of the effective microorganism fermentation extract (EM-X) as
      well as the second generation (EM-X2) on cancer cell lines in vitro. The possible
      anti-angiogenic potential of EM-X has not been reported. Herein we show that
      using the concentrated EM-X, the growth of human umbilical cord endothelial cells
      (HUCE) was significantly inhibited in vitro. Enzyme linked immunosorbent assay
      suggested that the concentrated EM-X is able to reduce the level of vascular
      endothelial growth factor (VEGF) from Hep3B hepatocellular carcinoma (HCC) cells.
      The conditioned culture medium obtained from the concentrated EM-X incubated
      Hep3B HCC cells possessed significant antiproliferative effect on the HUCE cells.
      Moreover, in vivo chick chorioallantoic membrane assay further demonstrated that
      the concentrated EM-X is able to greatly inhibit the basic fibroblast growth
      factor induced angiogenesis from chick embryo experiment. We speculate that the
      anti-cancer potential of this concentrated EM-X involved growth inhibition on
      cancer cell and antiangiogenic effect on HUCE cells.

PMID- 17016631
TI  - Com-1/p8 acts as a putative tumour suppressor in prostate cancer.
AB  - Com-1, candidate of metastasis-1, also known as p8, is a recently discovered
      molecule with a putative role in determining the metastatic nature of cancer
      cells. We have investigated the expression of Com-1 in normal and malignant human
      prostate tissues and its molecular interaction within prostate cancer cells. The
      expression of Com-1 in human prostate tissues and prostate cancer cell lines was
      assessed at both the mRNA and protein levels, by RT-PCR and immunohistochemistry.
      The staining intensity of Com-1 was semiquantified using computer assisted image
      analysis. Full- length Com-1 cDNA was isolated from normal mammary tissues.
      Ribozyme transgenes that specifically target human Com-1 were constructed using
      the pEF6/V5-His vector. The growth of prostate cancer cells in vitro and tumour
      growth in vivo (athymic mice model) following Com-1 overexpression in prostate
      cancer cells were determined. In normal prostate tissues, the epithelial cells
      strongly stained Com-1, both in the cytoplasm and in the nucleus. In contrast,
      prostate cancer cells in tumour tissue showed substantially reduced Com-1
      staining levels (p < 0.05 compared to normal cells for both cytoplasmic and
      nucleus staining), whereas the prostate cancer cell lines PC-3, DU145 and CA
      HPV10 widely expressed Com-1. Transfection of these cells with hammerhead
      ribozyme transgenes resulted in the loss of expression of the Com-1 transcript.
      Using an in vitro invasion assay we found that the loss of Com-1 from prostate
      cancer cells increased their invasiveness. Knockout of Com-1 also resulted in the
      accelerated growth of all three cell lines. Forced overexpression of Com-1/ p8 in
      prostate cancer cells was able to reverse the changes in invasiveness and growth
      seen with the Com-1 knock-out cells. In a spontaneous tumour model, it was
      demonstrated that PC-3 cells with forced overexpression of Com-1 (PC-3com1Exp)
      had a significantly slower rate of growth compared with control cells (tumour
      size 36.6 +/- 31.2 vs 114.3 +/- 68.1 mm3, for tumours from PC-3com1Exp and
      control PC-3 cells, respectively, p = 0.0023). In conclusion, Com-1/p8 was
      expressed at lower levels in human prostate cancer cells compared with normal
      epithelial cells. Com-1/p8 levels are inversely correlated with the invasiveness
      and growth of prostate cancer cells in vitro and the overexpression of Com-1
      reduced the growth of prostate tumours in vivo. Com-1/p8 is a potential tumour
      suppressor in human prostate cancer.

PMID- 17016632
TI  - Pro-oxidative effects of tea and polyphenols, epigallocatechin-3-gallate and
      epigallocatechin, on G6PD-deficient erythrocytes in vitro.
AB  - Glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects are vulnerable to
      chemical-induced hemolysis if exposed to oxidative agents. Recent studies
      reported that green tea and its constituents might act as pro-oxidants. Our
      objective was to investigate effects of tea and its polyphenolic components on
      the oxidative status of human G6PD-deficient erythrocytes. Erythrocytes of G6PD
      deficient (n = 8) and normal (n = 8) subjects were incubated with water extracts
      of 3 types of tea samples (black tea, green tea and decaffeinated green tea
      extract) and 6 polyphenols. The resulting levels of reduced glutathione (GSH) and
      glutathione disulphide (GSSG), methemoglobin and plasma hemoglobin were
      quantified by HPLC and biochemical assays. The tea extracts significantly reduced
      GSH and increased GSSG levels in G6PD-deficient erythrocytes in a dose-dependent
      manner (0.5-10 mg/ml), but not in normal erythrocytes. Similar dose-dependent
      responses to (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate
      (EGCG), but not to the other polyphenols, were observed. In G6PD-deficient cells,
      GSH was reduced by 43.3% (EGC at 0.05 mg/ml) and 33.3% (EGCG at 0.5 mg/ml),
      compared with pre-challenged levels. The concentration of methemoglobin was
      increased significantly when challenged with tea extracts, and EGC. Plasma
      hemoglobin levels were higher in G6PD-deficient samples after exposure to tea
      extracts, EGCG, EGC and gallic acid, compared with those in normal blood. Tea
      extracts and polyphenols significantly altered the oxidative status of G6PD
      deficient erythrocytes in vitro as demonstrated by the decrease of GSH, and
      increased GSSG, methemoglobin and plasma hemoglobin. Our data caution against the
      excessive consumption of concentrated tea polyphenolic products by G6PD-deficient
      subjects.

PMID- 17016633
TI  - Development and evaluation of a colorimetric PCR system for the detection and
      typing of human papillomaviruses.
AB  - In developing countries, the introduction of human papillomaviruses (HPV) DNA
      testing as an adjunct to cytological screening programs has been delayed due to
      the lack of high performance and cost effective diagnostic nucleic acid methods.
      In this study we report the development and evaluation of the L1HPVPCR, a PCR
      based method for the detection and typing of five of the most prevalent high-risk
      HPV types. The L1HPVPCR assay combines amplification with the MY09/11 HPV
      consensus primer system, liquid hybridization of the PCR products with no
      radioactive probes and enzyme immunoassay analysis. The technique is a user
      friendly system that allows accurate HPV DNA detection and typing with
      inexpensive instrumentation that could be performed with not sophisticated
      reagents in almost any laboratory. Different cutoff points for generic and
      specific HPV detection were determined using reproducibility analysis and
      receiver operating characteristic curves to ensure good analytical sensitivity
      and clinical effectiveness. We used the L1HPVPCR assay to estimate the prevalence
      of HPV infection in 127 women at risk of cervical cancer from the city of Rosario
      (Argentina), where no epidemiological data has been previously reported. Further,
      we explored the clinical utility of the L1HPVPCR assay respect the Pap smear
      using a combined diagnosis of cytology, histology and colposcopy as gold
      standard. In conclusion, our results indicate that the assay described here
      provides a tool for accurate HPV DNA testing and could be applied in regions
      where no commercial tests are available.

PMID- 17016634
TI  - Molecular characterization of well-differentiated human thyroid carcinomas by
      cDNA arrays.
AB  - Well-differentiated papillary and follicular thyroid carcinomas are the two most
      common types of thyroid cancer. Although cancerous cells in both types
      phenotypically resemble the epithelial follicular cell, the tumors display
      different histological characteristics and clinical outcomes. Molecular defects
      contributing to the separate development pathways remain largely unclear. We
      evaluated gene expression profiles to generate a detailed molecular
      characterization of the two tumor types, attempting to detect novel diagnostic
      and clinical markers. Gene expression profiling of 46 thyroid samples (16
      papillary carcinomas, 13 follicular carcinomas and 17 normal thyroid specimens)
      was performed by using high-density human UniGene cDNA arrays. The identification
      of differentially expressed genes was based on a comparison of signal intensity
      ratios of tumor versus normal tissues. A cross-validation of individual filter
      array hybridizations and real-time PCR analysis of selected genes were carried
      out to confirm data reproducibility and reliability. The majority of genes with
      altered expression were found in both papillary and follicular carcinomas,
      reflecting a close relationship between the two tumor types. However, 123 genes
      consisting of 45 known and 78 unknown genes were shown to be differentially
      expressed between papillary and follicular carcinomas. Follicular variants of
      papillary carcinoma, clustered together with classical papillary carcinoma, could
      be differentiated from follicular carcinoma. Our study revealed a set of genes
      differentiating follicular carcinoma from classical papillary carcinoma and
      follicular variant. The data generated in this study could serve as a useful
      source for further investigation of pathways of papillary and follicular
      differentiation of thyroid cancer.

PMID- 17016635
TI  - Pathotropic nanoparticles for cancer gene therapy Rexin-G IV: three-year clinical
      experience.
AB  - Metastatic cancer is a life-threatening illness with a predictably fatal outcome,
      thereby representing a major unmet medical need. In 2003, Rexin-G became the
      world's first targeted injectable vector approved for clinical trials in the
      treatment of intractable metastatic disease. Uniquely suited, by design, to
      function within the context of the human circulatory system, Rexin-G is a
      pathotropic (disease-seeking) gene delivery system bearing a designer killer
      gene; in essence, a targeted nanoparticle that seeks out and selectively
      accumulates in metastatic sites upon intravenous infusion. The targeted delivery
      of the cytocidal gene to primary tumors and metastatic foci, in effective local
      concentrations, compels both cancer cells and tumor-associated neovasculature to
      self-destruct, without causing untoward collateral damage to non-target organs.
      In this study: i) we report the results of three distinctive clinical studies
      which demonstrate the initial proofs of concept, safety, and efficacy of Rexin-G
      when used as a single agent for advanced or metastatic cancer, ii) we introduce
      the quantitative foundations of an innovative personalized treatment regimen,
      designated the 'Calculus of Parity', based on a patient's calculated tumor
      burden, iii) we propose a refinement of surrogate end-points commonly used for
      defining success in cancer therapy, and iv) we map out a strategic plan for the
      accelerated approval of Rexin-G based on the oncologic Threshold of Credibility
      paradigm being developed by the Food and Drug Administration.

PMID- 17016636
TI  - Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from
      Rauwolfia vomitoria.
AB  - The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally
      to treat a variety of ailments. A bioactive beta-carboline alkaloid, alstonine,
      present in this extract was previously shown to have anti-cancer activity against
      cancer cell lines. This study considers the potential anti-prostate cancer
      activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract
      standardized for beta-carboline alkaloids was tested for ability to influence the
      growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay
      was used to measure cell growth, and cell cycle analyses were conducted with flow
      cytometry. Western blot detection of PARP cleavage and accumulation of cells
      containing sub-genomic DNA indicated induction of apoptosis. Pathway specific
      microarray analyses were utilized to identify the effect of Rauwolfia extract on
      the expression of 225 genes. Mice xenografted with LNCaP cells were treated with
      the extract or placebo control, and tumor growth was measured for 5 weeks. The
      effects of the extract on xenografted tumor cell proliferation and apoptosis were
      measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract
      decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced
      the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was
      induced only at the highest concentration tested (500 microg/ml) which was
      confirmed by detection of cells containing sub-genomic DNA. The expression of
      genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia
      treatment, including that of GADD153 and MDG. The expression of a few cell cycle
      genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were
      confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the
      groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis
      test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the
      growth and cell cycle progression of LNCaP cells, in vitro and in vivo.

PMID- 17016637
TI  - Membrane vesicles shed by oligodendroglioma cells induce neuronal apoptosis.
AB  - In order to investigate the mechanism by which oligodendrogliomas cause neuronal
      damage, media conditioned by G26/24 oligodendroglioma cells, were fractionated
      into shed vesicles and vesicle-free supernatants, and added to primary cultures
      of rat fetal cortical neurons. After one night treatment with vesicles, a
      reproducible, dose-dependent, inhibitory effect on neurite outgrowth was already
      induced and, after 48-72 h of incubation, neuronal apoptosis was evident. Vesicle
      free supernatants and vesicles shed by NIH-3T3 cells had no inhibitory effects on
      neurons. Western blot analyses showed that treated neurons expressed a decreased
      amount of neurofilament (NF), growth-associated protein (GAP-43) and microtubule
      associated protein (MAP-2). Moreover procaspase-3 and -8 were activated while Bcl
      2 expression was reduced. Vesicles were found positive for the proapoptotic
      molecule, Fas-ligand (Fas-L), and for the B isoform of Nogo protein, a myelin
      component with inhibitory effects on neurons. Nogo B involvement in the vesicle
      effects was analyzed both by testing the neutralizing capability of anti-Nogo
      antibodies and by removing the Nogo receptor from neurons by phospholipase C
      digestion. These treatments did not revert the vesicle effects. To test the role
      of Fas-L, vesicles were treated with functional anti-Fas-L monoclonals. Vesicle
      inhibitory and proapoptotic effects were reduced. Vesicles shed by ovarian
      carcinoma cells (OvCa), which are known to vehicle biologically active Fas-L, had
      similar effects on neurons to those of oligodendroglioma vesicles, and their
      inhibitory effects were also reduced by anti Fas-L antibodies. We therefore
      conclude that vesicles shed by G26/24 cells induce neuronal apoptosis at least
      partially by a Fas-L mediated mechanism.

PMID- 17016638
TI  - Effective anti-angiogenic therapy of established tumors in mice by naked anti
      human endoglin (CD105) antibody: differences in growth rate and therapeutic
      response between tumors growing at different sites.
AB  - We investigated anti-angiogenic/vascular targeting therapy of established tumors
      in immunocompetent mice using an anti-human endoglin (EDG; CD105) monoclonal
      antibody (mAb) SN6j. SN6j weakly cross-reacted with murine endothelial cells but
      reacted neither with colon-26 murine colon carcinoma cells nor with 4T1 murine
      mammary carcinoma cells. Systemic administration of naked (unconjugated) SN6j
      showed significant growth suppression of established tumors of colon-26 and 4T1
      cells in immunocompetent BALB/c mice (P<0.05). Moreover, the overall survival
      rate of SN6j-treated mice was significantly higher than that of control IgG
      treated mice (P<0.01). During these studies, we found that two different types of
      tumor formed in BALB/c and immunodeficient SCID mice when three different types
      of tumor cells (colon-26, 4T1 and MCF-7 human breast cancer cells) were
      inoculated subcutaneously. One type of tumor grew in the skin-side tissue (i.e.,
      epidermis, corium, or subcutis), and mainly invaded into the corium and
      epidermis. The other type grew in the muscle-side tissue (i.e., fascia, muscle,
      or peritoneum/pleura). We termed the former SS tumors and the latter MS tumors.
      MS tumors grew faster than SS tumors. This differential growth of MS and SS
      tumors was observed in three different animal models, i.e., colon-26 tumors and
      4T1 tumors in BALB/c mice, and MCF-7 tumors in SCID mice. In the therapeutic
      study of colon-26 and 4T1 tumors with SN6j, MS tumors were less responsive to
      therapy than SS tumors although SN6j showed significant antitumor efficacy
      against both tumors (P<0.05). The results show that antitumor therapy can yield
      different therapeutic outcomes depending on the tumor growth sites even for the
      same tumor. A differential survival between mice with the two types of tumor was
      also observed when mice were untreated (P<0.01).

PMID- 17016639
TI  - Elevated cell migration, invasion and tumorigenicity in human KB carcinoma cells
      transfected with COX-2 cDNA.
AB  - In order to investigate the involvement of cyclooxygenase (COX)-2 in cell growth
      and invasion of oral cancer, a human epidermoid carcinoma cell line KB minimally
      expressing COX-2 protein was transfected with COX-2 cDNA and these activities
      were compared with mock-transfected KB in vitro and in vivo. KB/COX-2 clones
      showed a similar growth rate in vitro compared to KB/neo clones, but demonstrated
      significantly increased PGE2 production, cell migration and invasion. These
      KB/COX-2 clones markedly expressed MMP-9, pro-MMP-2 and activated-MMP-2 as
      compared to KB/neo clones in gelatin zymography. Western blot analysis showed
      that expression of MT1-MMP, Rho and Rac 1 in KB/COX-2 clones were stronger than
      that in KB/neo clones, but expression of TIMP-1 and TIMP-2 were weaker in KB/COX
      2 clones than in KB/neo clones. When these cells were inoculated subcutaneously
      into nude mice, tumorigenicity and tumor growth were significantly elevated in
      KB/COX-2 tumors than in KB/neo tumors, and the gelatinase activity was much
      stronger in KB/COX-2 tumor tissues than in KB/neo tumor tissues in film in situ
      zymography. The orthotopic inoculation of cells to the oral floor showed that
      local invasion was pronounced in KB/COX-2 tumors. These results indicated that
      overexpression of COX-2 elevated tumorigenicity, tumor growth and invasion of
      human KB carcinoma cells via up-regulated MMP and Rho family small GTPases and
      down-regulated TIMP activities.

PMID- 17016640
TI  - Cytoplasmic expression of p21CIP1/WAF1 is correlated with IKKbeta overexpression
      in human breast cancers.
AB  - Regulation of cytoplasmic p21CIP/WAF1 (p21) is of great clinical significance in
      molecular oncology due to its identification as an antiapoptotic factor, a poor
      survival predictor as well as a drug-resistance inducer. A retrospective study of
      the immunohistochemical (IHC) profiles of 128 human primary breast cancers showed
      that increased total and cytoplasmic p21 expression were highly associated with
      the expression of IkappaB kinase beta (IKKbeta), the major catalytic subunit of
      the IKK complex and another crucial player in tumorigenesis and drug resistance.
      The causal relationship study based on cultured cell lines, MDA-MB-453 and MCF-7,
      confirmed that IKKbeta overexpression did upregulate protein levels of total and
      cytoplasmic p21. Mechanistic investigation demonstrated that IKKbeta increased
      p21 expression through upregulation of p21 mRNA level. Moreover, by Western
      blotting, IKKbeta was found to be able to upregulate Akt phosphorylation on Ser
      473. This novel finding indicated that IKKbeta could mediate cytoplasmic p21
      accumulation via activation of its downstream target Akt, which was known to
      phosphorylate p21 and lead to cytoplasmic localization of p21.

PMID- 17016641
TI  - P53-dependent radiosensitizing effects of Hsp90 inhibitor 17-allylamino-17
      demethoxygeldanamycin on human oral squamous cell carcinoma cell lines.
AB  - Development of new molecular target therapeutic agents is expected to improve
      clinical outcome, ideally with efficacy in both single and combined treatment
      modalities. Because of the potential for affecting multiple signaling pathways,
      inhibition of the molecular chaperone heat shock protein 90 (Hsp90) may provide a
      strategy for enhancing tumor cell radiation sensitivity. Therefore, we have
      investigated the effects of Hsp90 inhibitor 17-Allylamino-17
      demethoxygeldanamycin (17-AAG) on radiation sensitivity of human tumor cells in
      vitro. We evaluated the effects of 17-AAG using oral squamous cell carcinoma
      (OSCC) cell lines (HSC2, HSC3 and HSC4), including two types of SAS cells with a
      wild-type (SAS/neo), or a mutated p53 status (SAS/Trp248). Apoptosis and
      clonogenic survival were examined after exposure of the cells to radiation. For
      mechanistic insight, we analyzed cell cycle, several signaling factors and
      molecular markers including Akt, Raf-1, p38 MAPK, Cdc25B, Cdc25C, Cdk2 and p21.
      Treatment of OSCC cell lines with 17-AAG resulted in cytotoxicity and, when
      combined with radiation, enhanced the radiation response. However, the responses
      depended on p53 status. 17-AAG enhanced the radiation sensitivity significantly
      and induced apoptosis in the SAS/neo cell which has a wild-type p53. But the
      radiation sensitizing effect of 17-AAG was limited in the SAS/Trp248 cell which
      has a mutated p53. We also measured the total levels of several prosurvival and
      cell cycle signaling proteins. Akt, Raf-1 and Cdc25C expression were down
      regulated in 17-AAG-treated cells. These data indicate that 17-AAG inhibits the
      proliferation and enhances the radiation sensitivity of human OSCC cells in
      various levels. However, enhancement of radiation sensitivity by the Hsp90
      inhibitor depended on p53 status. Therefore, Hsp90 therapy combined with
      radiation might synergize with conventional therapies in patients with wild-type
      p53.

PMID- 17016642
TI  - Fulminant liver failure triggered by therapeutic antibody treatment in a mouse
      model.
AB  - Monoclonal antibodies are finding ever increasing therapeutic applications.
      However, lethal liver damage has been reported following monoclonal antibody
      (mAb) treatment in combination with subtoxic doses of cytotoxic drugs. In this
      study, mice were intravenously injected with 200 microg/mouse of anti-CD8 (anti
      Lyt-2.2), anti-CD4 (GK1.5) or anti-B220 (RA3-6B2) mAb. Subsequently, mice were
      administered 15 mg azoxymethane (AOM) per kg body weight by subcutaneous
      injection. Unexpectedly, all mice pretreated with mAb died within 72 h of a
      single injection of AOM. The injection of mAb-coated spleen cells accelerated the
      induction and the severity of liver disease. We found that mAb treatment
      activates Kupffer cells to produce inflammatory cytokines such as TNF-alpha and
      IL-12, and induces the expression of FasL on Kupffer and NKT cells. The
      concomitant upregulation of Fas on hepatocytes increases the susceptibility of
      the liver to apoptotic signals, and subsequent treatment with AOM causing
      mitochondrial injury synergistically induces lethal liver damage. Consistently,
      the lethal liver damage was abrogated in mice which were deficient for Kupffer
      cells, NKT cells or Fas-antigen. In conclusion, we have demonstrated a potential
      risk of lethal fulminant liver damage in the concomitant use of therapeutic
      antibodies and cytotoxic drugs. A possible side effect of antibody therapy is
      mediated through activation of the immune system, the very mechanism of action on
      which this treatment depends. In this context, the risk of combining therapeutic
      antibodies with other agents, particularly cytotoxic drugs, requires careful
      consideration.

PMID- 17016643
TI  - Expression profile of the tumor suppressor genes DLC-1 and DLC-2 in solid tumors.
AB  - Several years after the isolation of deleted in liver cancer 1 (DLC-1), a gene
      that encodes a Rho GTPase activating protein, the closely related DLC-2 gene was
      identified. DLC-1 and DLC-2 are approximately 50% identical and share the same
      SAM-RhoGAP-START domain organization. Since DLC-1 and -2 are located at
      chromosome regions that are commonly deleted in cancer cells and have been found
      to function as tumor suppressor genes, we sought to compare their expression
      profiles in several common types of cancer and to determine whether dlc1 and dlc2
      proteins cooperate in tumor development. Using cancer-profiling arrays, we
      detected for the first time down-regulation of DLC-1 expression in renal, uterine
      and rectal cancers and down-regulation of DLC-2 expression in lung, ovarian,
      renal, breast, uterine, gastric, colon and rectal tumors. Since DLC-1 also
      functions as a metastasis suppressor gene in breast cancer, DLC-1 and DLC-2
      expression were examined in a series of primary ductal carcinomas derived from
      patients with regional lymph node metastases. Using quantitative RT-PCR we
      detected a significantly lower expression of DLC-1 and DLC-2 in high percentage
      of tumors, suggesting that deficiency of either DLC gene facilitates
      dissemination of breast carcinoma cells to secondary sites. We examined DLC-2
      expression in DLC-1-negative cell lines derived from human breast, non-small cell
      lung, and hepatocellular carcinomas, that could be rendered less or non
      tumorigenic by ectopic expression of DLC-1. DLC-2 transcripts were detected in
      all cell lines, indicating that none of the cells were deficient in both members
      of the DLC family. This comparative expression analysis of DLC-1 and -2
      identifies down-regulation of the two emerging bona fide tumor suppressor genes
      in additional types of solid tumors. The large spectrum of cancers with
      dysregulated DLC genes underlines the involvement of this family of genes in
      cancer development.

PMID- 17016644
TI  - Epithelial-mesenchymal transition induced by the stromal cell-derived factor
      1/CXCR4 system in oral squamous cell carcinoma cells.
AB  - Epithelial-mesenchymal transition (EMT) refers to critical events occasionally
      observed during tumor progression, including invasion and metastasis, by which
      cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived
      factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral
      squamous cell carcinoma (SCC), we have explored the possibility that this system
      might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional
      CXCR4 and lymph node metastatic potential, were found to lose their epithelial
      cell morphology due to SDF-1. In this context, the downregulation of epithelial
      markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of
      mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation
      of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase
      (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein
      kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I
      collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions,
      but the effect was impaired by treatment with Wortmannin. These results suggested
      that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node
      metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.

PMID- 17016645
TI  - Correlation of glypican-1 expression with TGF-beta, BMP, and activin receptors in
      pancreatic ductal adenocarcinoma.
AB  - Glypican1 (GPC1) is a cell surface heparan sulfate proteoglycan that acts as a co
      receptor for heparin-binding growth factors as well as for members of the TGF
      beta family. GPC1 plays a role in pancreatic cancer by regulating growth factor
      responsiveness. In view of the importance of members of the TGF-beta family in
      pancreatic cancer, in the present study, the role of GPC1 in TGF-beta, BMP and
      activin signaling was analyzed. Quantitative RT-PCR and immunohistochemistry were
      utilized to analyze GPC1 and TGF-beta, BMP and activin receptor expression
      levels. Panc-1 and T3M4 pancreatic cancer cells were transfected in a stable
      manner with a GPC1 antisense expression construct. Anchorage-dependent and 
      independent growth was determined by MTT and soft agar assays. TGF-beta1, activin
      A and BMP-2 responsiveness was determined by MTT assays and immunoblotting with
      p21, p-Smad1, and p-Smad2 antibodies. QRT-PCR demonstrated increased GPC1 mRNA
      levels in pancreatic ductal adenocarcinoma (PDAC) compared to normal pancreatic
      tissues (NPT), as described previously. There was a significant correlation
      between GPC1 mRNA levels and TbetaRII, act-R1a, act-R1b, act-R2a, BMP-R1a, and
      BMP-R2 mRNA expression in NPT. In contrast, GPC1 mRNA expression correlated
      directly with act-R1a and BMP-R1a in N0 PDAC cases and with act-R2a and BMP-R1a
      in lymph node positive cases. Down-regulation of GPC1 resulted in increased
      doubling time in Panc-1 but not in T3M4 cells, and decreased anchorage
      independent growth in both cell lines. GPC1 down-regulation resulted in a
      slightly altered response towards TGF-beta1, activin-A and BMP-2 in terms of
      growth, p21 induction and Smad2 phosphorylation. In conclusion, enhanced GPC1
      expression correlates with BMP and activin receptors in pancreatic cancer. GPC1
      down-regulation suppresses pancreatic cancer cell growth and slightly modifies
      signaling of members of the TGF-beta family of growth factors.

PMID- 17016646
TI  - Effects of RNAi-mediated Smad4 silencing on growth and apoptosis of human
      rhabdomyosarcoma cells.
AB  - Transforming growth factor-beta (TGF-beta) signals through membrane-bound
      heteromeric serine/threonine kinase receptors. Upon ligand binding, TGF-beta
      activates intracellular Smad proteins and regulates proliferation and apoptosis
      in various cell types. To demonstrate the effects of TGF-beta/Smad signal on
      growth and apoptosis of human embryonal rhabdomyosarcoma (RMS) cells, a strategy
      of RNAi-mediated 'gene silencing' of Smad4 was used to interrupt endogenous TGF
      beta/Smad signaling in an RMS cell line, RD, and the regulation of exogenous TGF
      beta1 to growth and apoptosis of the cells was also determined. Physiologically,
      TGF-beta/Smad signaling was essential for the normal growth of RD. The
      interruption of endogenous TGF-beta/Smad signaling by RNAi significantly
      suppressed the growth of RD cells and dramatically induced apoptosis of RD cells.
      Exogenous TGF-beta1 also inhibited the growth of RD cells, but had no effect on
      apoptosis. It also partially counteracted the growth inhibition and apoptosis
      induced by Smad4 silencing in RD cells. These findings provide a new insight into
      how TGF-beta/Smad signaling regulates the growth and apoptosis of cancer cells.
      Moreover, as a powerful tool, shRNA interference suppresses endogenous Smad4 gene
      expression and subsequently modulates cell growth and apoptosis, which may
      provide a novel basis for the development of rational intervention strategies in
      RMS therapy.

PMID- 17016647
TI  - Epidermal growth factor receptor analyses in colorectal cancer: a comparison of
      methods.
AB  - EGFR immunohistochemistry (IHC) status is not a reliable predictive marker for
      response to EGFR-targeted therapies. The present study compares the EGFR status
      at DNA, RNA and protein level. Blood samples, corresponding normal colon and
      colorectal cancer tissue were collected from 199 colorectal cancer (CRC)
      patients. EGFR status was evaluated by FISH analysis, real-time RT-PCR, ELISA and
      IHC. A polymorphism in the EGFR promoter was evaluated by PCR analysis. The EGFR
      levels by different methods were mutually compared. Seventy-eight percent of
      primary tumours and corresponding lymph nodes had equivalent EGFR status (28/34).
      There was a tendency to higher median protein level (by ELISA) in IHC positive
      patients compared to IHC negative patients (p=0.086). The median EGFR gene
      expression level was significantly lower in tumours than in the normal colon with
      no difference according to IHC status. No tumours had increased gene copy number
      by FISH. EGFR Sp1-216 polymorphism analysis showed a tendency for different EGFR
      tumour protein levels and gene expression levels according to the different
      genotypes. The results show a poor correlation between EGFR status at DNA, RNA
      and protein level. The predictive value of a combination of methods needs further
      evaluation in the clinical setting.

PMID- 17016648
TI  - Vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde-elicited apoptosis
      and G2/M arrest of Jurkat cells proceeds concurrently with DNA-PKcs cleavage and
      Akt inactivation.
AB  - Vanillin, a naturally occurring food component, has been reported to have anti
      mutagenic and anti-metastatic potentials, and to inhibit DNA-PKcs activity.
      However, vanillin itself exhibits very weak antiproliferative activity. We
      explored the effects of bromovanin (6-bromine-5-hydroxy-4-methoxybenzaldehyde), a
      novel vanillin derivative, on survival and cell-cycle progression of human Jurkat
      leukemia cells. Treatment with >10 microM bromovanin significantly elicited
      apoptosis and G2/M arrest in Jurkat cells in a dose- and time-dependent manner.
      Bromovanin-induced DNA double-strand breaks (DSB) were demonstrated by means of
      comet assay as well as detection of phosphorylated H2AX, a sensitive indicator of
      DNA DSBs. Immuno-hybridization analysis revealed that the cleavage of procaspase
      3 and DNA-PKcs occurred concurrently with bromovanin-induced apoptosis.
      Furthermore, phosphorylated Akt protein (Ser473), which is catalyzed by DNA-PKcs,
      as well as phosphorylated GSK3beta (a substrate of activated Akt), markedly
      decreased in bromovanin-treated Jurkat cells, suggesting that bromovanin leads to
      inactivation of Akt pathway via cleaving DNA-PKcs. These multiple effects,
      associated with the regimen of cancer therapeutic strategies, make bromovanin
      very appealing for future development as a novel anticancer drug.

PMID- 17016649
TI  - A dog pedigree with familial medullary thyroid cancer.
AB  - Multiple endocrine neoplasia (MEN) is defined as concurrent neoplasia or
      hyperplasia in more than one endocrine gland. MEN is well known in humans and has
      also been reported in small animals. We report on a dog family of a mixed breed
      with Alaskan malamute as a major influence, where three members developed thyroid
      carcinomas and another dog had clinical signs mimicking the other three but
      without a confirmed diagnosis. The age of onset of the tumour was between 96-109
      months. Clinical, biochemical and immunohistochemical examinations revealed that
      the affected individuals typically demonstrated symptoms including calcitonin
      positive thyroid cancer, hypothyroidism and chronic dermatitis. In addition,
      elevated serum calcium and multinodular adrenocortical hyperplasia were
      demonstrated in a single member. The diagnosis observed is similar to the
      familial form of medullary thyroid carcinoma (FMTC) in human. This is the first
      report of FMTC in dog. Up to 95% of FMTC and MEN2 is known to be caused by
      activating mutations in the RET gene. The dog Ret gene was analysed as a
      candidate in this pedigree. The complete dog Ret genomic sequence was predicted
      in silico. The lack of demonstratable Ret mutation suggests the involvement of
      alternative predisposing mutation in this pedigree. The unique occurrence of
      familial MTC makes this potentially an important model in further defining the
      genetic basis of MTC.

PMID- 17016650
TI  - Outcome-based profiling of astrocytic tumours identifies prognostic gene
      expression signatures which link molecular and morphology-based pathology.
AB  - Astrocytomas are intracranial malignancies for which invasive growth and high
      motility of tumour cells preclude total resection; the tumours usually recur in a
      more aggressive and, eventually, lethal form. Clinical outcome is highly variable
      and the accuracy of morphology-based prognostic statements is limited. In order
      to identify novel molecular markers for prognosis we obtained expression profiles
      of: i) tumours associated with particularly long recurrence-free intervals, ii)
      tumours which led to rapid patient death, and iii) tumour-free control brain.
      Unsupervised data analysis completely separated the three sample entities
      indicating a strong impact of the selection criteria on general gene expression.
      Consequently, significant numbers of specifically expressed genes could be
      identified for each entity. An extended set of tumours was then investigated by
      RT-PCR targeting 12 selected genes. Data from these experiments were summarised
      into a sample-specific index which assigns tumours to high- and low-risk groups
      as successfully as does morphology-based grading. Moreover, this index directly
      correlates with definite survival suggesting that integrated gene expression data
      allow individualised prognostic statements. We also analysed localisation of
      selected marker transcripts by in situ hybridization. Our finding of cell
      specificity for some of these outcome-determining genes relates global expression
      data to the presence of morphological correlates of tumour behaviour and, thus,
      provides a link between morphology-based and molecular pathology. Our
      identification of expression signatures that are associated individually with
      clinical outcome confirms the prognostic relevance of gene expression data and,
      thus, represents a step towards eventually implementing molecular diagnosis into
      clinical practice in neuro-oncology.

PMID- 17016651
TI  - Reduced lecithin:retinol acyltransferase expression in human breast cancer.
AB  - Retinoids, vitamin A (retinol) and related metabolites, have been shown to be
      important in regulating cell growth and differentiation. We have shown that
      expression of the enzyme lecithin:retinol acyltransferase (LRAT), which converts
      retinol to retinyl esters, is reduced in several human carcinomas as compared
      with adjacent normal tissue from the same organs. The purpose of this research
      was to determine if aspects of retinoid signaling are impaired in human breast
      cancer. We evaluated LRAT protein expression in neoplastic and adjacent, non
      neoplastic glandular breast tissue specimens from human patients. We evaluated 26
      specimens from patients diagnosed with breast cancer between 2003 and 2005.
      Representative paraffin-embedded tissue blocks from each tumor, with each
      containing adjacent non-neoplastic glandular breast tissue, were examined by
      immunohistochemistry with affinity purified antibodies to human LRAT protein.
      LRAT protein was prominently detected throughout the non-neoplastic glandular
      breast tissue in all of the specimens. Areas of ductal carcinoma in situ and well
      differentiated invasive breast carcinomas showed an intensity of staining with
      the LRAT antibody which was similar to that of the adjacent normal tissue.
      Expression of LRAT protein progressively decreased with a reduction in the degree
      of tumor differentiation in invasive breast carcinomas. LRAT protein levels
      correlate better with the degree of ductal tumor differentiation than does
      estrogen receptor status in this study. Furthermore, normal human breast
      epithelium exhibits intense LRAT staining, indicating a major role for LRAT in
      human breast physiology.

PMID- 17016652
TI  - Involvement of RHO GTPases and ERK in synuclein-gamma enhanced cancer cell
      motility.
AB  - Synuclein-gamma is aberrantly expressed in more than 70% of stage III/IV breast
      and ovarian carcinomas. Ectopic overexpression of synuclein-gamma enhanced MDA-MB
      435 cell migration in vitro and metastasis in a nude mouse model. However, the
      mechanism of how synuclein-gamma promotes cell motility is not clear. In our
      previous studies, we showed that synuclein-gamma overexpression activates ERK. In
      the present study, we overexpressed synuclein-gamma in several breast and ovarian
      cancer cell lines and evaluated the effect of synuclein-gamma on the activity of
      small G-protein RHO family members. We found that at least one of the
      RHO/RAC/CDC42 GTPases showed a higher level of the GTP-bound active form.
      Consistent with their role in regulating the intracellular motile machinery,
      inhibition of the RHO/RAC/CDC42 by C. difficile Toxin B blocked cell migration in
      both parental cells and synuclein-gamma overexpressing cells. The ERK inhibitor
      U0126 also blocked the cell migration in both parental cells and synuclein-gamma
      overexpressing cells. Collectively, our data indicate that synuclein-gamma might
      be involved in late stage breast and ovarian cancer metastasis by enhancing cell
      motility through activation of the RHO family small-GTPases and ERK.

PMID- 17016653
TI  - Apoptosis of U937 human leukemic cells by sodium butyrate is associated with
      inhibition of telomerase activity.
AB  - Sodium butyrate as a histone deacetylase inhibitor is known to exhibit anti
      cancer effects via the differentiation and apoptosis of various carcinoma cells.
      However, the mechanism by which sodium butyrate induces apoptosis and the
      involvement of telomerase activity during apoptosis is not completely understood.
      To investigate the underlying pathways, sodium butyrate's potential to induce
      apoptosis in human leukemic U937 cells and its effects on telomerase activity
      were investigated. Exposure of U937 cells to sodium butyrate resulted in growth
      inhibition and induction of apoptosis in a dose-dependent manner as measured by
      hemocytometer counts, fluorescence microscopy, agarose gel electrophoresis and
      flow cytometry analysis. The increase in apoptosis was associated with the up
      regulation in pro-apoptotic Bax expression, and down-regulation of anti-apoptotic
      Bcl-2 and Bcl-XL. Sodium butyrate treatment also inhibited the levels of cIAP
      family members and induced the activation of caspase-3. Furthermore, sodium
      butyrate markedly inhibited the activity of telomerase and the expression of
      human telomerase reverse transcriptase (hTERT), a main determinant of the
      telomerase enzymatic activity, was progressively down-regulated by sodium
      butyrate. Taken together, it is suggested that sodium butyrate can be a promising
      chemopreventive agent for leukemic cells and changes in Bcl-2 family expressions,
      as well as telomerase activity may, play critical roles in sodium butyrate
      induced apoptosis in U937 cells.

PMID- 17016654
TI  - Differential control of growth, cell cycle progression, and gene expression in
      human estrogen receptor positive MCF-7 breast cancer cells by extracts derived
      from polysaccharopeptide I'm-Yunity and Danshen and their combination.
AB  - The use of herbs has been the mainstay of treatment for a variety of human
      illnesses and is an essential part of culturally-based healing traditions in many
      societies and countries. Also, herbs, including Chinese herbs, are being
      incorporated as remedies for disease management and treatment in Western
      countries. In Traditional Chinese Medicine (TCM), herbal prescriptions are most
      frequently given to patients as complex formulations containing multiple herbs.
      Notably and unwittingly, this approach amounts to the administration of several
      chemical entities at once; the underlying theory is that interactions among the
      chemicals present in different herbs in a formula exert synergistic
      pharmacodynamic actions and neutralize the adverse effects and toxicities of
      specific individual chemicals. The effectiveness and mechanisms of this approach
      have not been well investigated or understood. A primary interest of this
      laboratory is to obtain experimental evidence that supports the fundamental
      mechanistic theme for the combinatorial herbal strategy described above and its
      potential application in preventing and treating breast cancer (BCa). In this
      study, we investigated the effects of 70% ethanolic extracts prepared from
      medicinal mushroom extract denoted I'm-Yunity and Danshen (Salvia miltiorrhizae
      Binge), alone and in combination, using MCF-7 cells as an in vitro model of
      estrogen receptor positive (ER+), low invasive BCa. Combination of I'm-Yunity and
      Danshen (referred to as I'm-Yunity-Plus) suppressed clonogenicity to a comparable
      degree as Danshen alone; both being significantly more active than I'm-Yunity.
      However, extract of Danshen was more active in inhibiting MCF-7 cell growth than
      I'm-Yunity-Plus. In comparison, I'm-Yunity elicited less growth inhibition. Flow
      cytometric analysis showed that I'm-Yunity-Plus induced partial block of G1/S
      transition in MCF-7 cells, whereas Danshen slowed down cell progression from G1/S
      into G2/M phases of the cell cycle. Treatment by I'm-Yunity did not affect cell
      cycle progression in MCF-7 cells; however, it promoted active induction of
      apoptosis. In addition, treatment with Danshen alone resulted in a pronounced
      reduction in the expression of Rb, cyclin D1, and p53, and also led to a
      diminution of p65 and p50 forms of NF-kappaB. The pronounced suppressive effects
      of Danshen on expression of the aforementioned genes were largely attenuated in
      cells treated with I'm-Yunity-Plus suggesting that ingredients in Danshen must
      have interacted with those in I'm-Yunity as to culminate in neutralization of the
      gene suppressive effects of Danshen. Additional support for such interactions was
      obtained by targeted cDNA array analysis using human tumor metastasis and BCa/ER
      signaling gene arrays. Taken together, our results are consistent with the
      interpretation that interaction exists between Danshen and I'm-Yunity and that
      I'm-Yunity-Plus may have efficacy in the treatment of BCa, particularly for
      patients with ER+ status.

PMID- 17016655
TI  - GnRH-II agonist [D-Lys6]GnRH-II inhibits the EGF-induced mitogenic signal
      transduction in human endometrial and ovarian cancer cells.
AB  - The majority of human endometrial and ovarian cancers express receptors for GnRH
      type I (GnRH-I). Their proliferation is time- and dose-dependently reduced by
      GnRH-I and its analogs. GnRH-I analogs activate a phosphotyrosine-phosphatase
      (PTP) and inhibit EGF-induced mitogenic signal transduction. Recently we found
      that GnRH type II (GnRH-II) and its agonist [D-Lys6]GnRH-II also have
      antiproliferative effects on these tumor cells which are significantly greater
      than those of GnRH-I agonists. In a more recent study, we showed that the
      antiproliferative activity of GnRH-II on human endometrial and ovarian cancer
      cell lines is not mediated through the GnRH-I receptor. The underlying signal
      transduction mechanisms of GnRH-II are still unknown. In this study we showed
      that the mitogenic effects of growth factors in endometrial and ovarian cancer
      cell lines were counteracted by GnRH-II agonist [D-Lys6]GnRH-II, indicating an
      interaction with the mitogenic signal transduction. We showed that [D-Lys6]GnRH
      II reduces EGF-induced auto-tyrosine-phosphorylation of EGF-receptors via
      activation of a PTP and that EGF-induced activation of mitogen-activated protein
      kinase was blocked in cells treated with [D-Lys6]GnRH-II. Furthermore, EGF
      induced expression of the immediate early gene c-fos was inhibited by treatment
      with [D-Lys6]GnRH-II. After knock-out of GnRH-I receptor expression, GnRH-II
      agonist [D-Lys6]GnRH-II still activated PTP and inhibited the EGF-induced
      mitogenic signal transduction. These data indicate, that the effects of GnRH-II
      are not due to a cross-reaction with the GnRH-I receptor. In conclusion these
      data suggest that the signaling of GnRH-II agonist [D-Lys6]GnRH-II is comparable
      to that of GnRH-I analogs.

PMID- 17016656
TI  - Suppression of SCC antigen promotes cancer cell invasion and migration through
      the decrease in E-cadherin expression.
AB  - Squamous cell carcinoma antigen (SCCA) is a useful tumor marker for diagnosis and
      management of squamous cell carcinoma. Recent studies have shown that SCCA can
      influence the behavior of cancer cells. It is well known that cell-cell adhesion
      is an important factor for the progression of cancer. The present study,
      therefore, was undertaken to investigate the effect of SCCA2 on the cell adhesion
      related molecule, E-cadherin, and cancer cell behavior. For this purpose,
      antisense SCCA2 cDNA was transfected into human uterine cancer cell lines, SKG
      IIIa and SiHa, which express SCCA2. Suppression of SCCA2 expression by antisense
      SCCA2 cDNA transfection decreased E-cadherin expression and promoted cell
      migration and invasion as well as the blockage of E-cadherin function by anti-E
      cadherin antibody administration. In conclusion, SCCA2 regulates cell migration
      and invasion via E-cadherin expression, suggesting that SCCA2 may be involved in
      cancer behavior such as invasion or metastasis.

PMID- 17016657
TI  - Cooperative effect of gefitinib and fumitremorgin c on cell growth and
      chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7
      cells.
AB  - The selective ER downregulator, fulvestrant, is currently approved as a second
      line endocrine therapy after onset of resistance to prior antiestrogen therapy in
      postmenopausal breast cancer patients. Resistance to antihormonal therapies is
      common and, therefore, we anticipate that fulvestrant-resistance will occur as
      well. The current study was undertaken to investigate the underlying molecular
      changes after fulvestrant-resistance and find new therapeutic targets and agents
      for fulvestrant-resistant breast cancer cells. We developed a unique fulvestrant
      resistant cell line (MCF-7/F), derived from MCF-7 estrogen receptor alpha
      (ERalpha)-positive human breast cancer cells, by culturing them in 1 microM
      fulvestrant containing medium for approximately 18 months. MCF-7/F cells became
      irreversibly ERalpha negative as withdrawal of fulvestrant did not alter the
      ERalpha-negative phenotype, determined by real-time PCR, Western blot analysis,
      and ERE-luciferase transfection assays. MCF-7/F cells grew in a hormone
      independent manner. Interestingly, MCF-7/F cells overexpressed both epidermal
      growth factor receptor (EGFR) and breast cancer resistant protein (BCRP).
      Gefitinib, a specific EGFR tyrosine kinase inhibitor, preferentially inhibited
      the growth of MCF-7/F cells relative to MCF-7 cells by inhibiting both MAPK44/42
      and Akt phosphorylation. MCF-7/F cells became less sensitive to chemotherapeutic
      agents such as mitoxantrone. Moreover, fumitremorgin C, a specific BCRP
      inhibitor, significantly increased the efficacy of mitoxantrone in MCF-7/F cells.
      Gefitinib increased the inhibitory effect of mitoxantrone on cell growth.
      Similarly, fumitremorgin C increased the inhibitory effect of gefitinib on cell
      growth, suggesting that there is a bidirectional crosstalk between EGFR and BCRP.
      More importantly, these results provide a molecular basis for using gefitinib,
      BCRP inhibitors, and chemotherapeutic agents as combination therapy approaches in
      fulvestrant-resistant breast cancer.

PMID- 17016658
TI  - Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human
      vascular smooth muscle cells via blocking PDGF receptor and Erk-1/2.
AB  - Platelet-derived growth factor (PDGF) has been known to induce vascular
      endothelial growth factor (VEGF) expression in human vascular smooth muscle cells
      (hVSMCs). We previously reported that Erk-1/2 and AP-1 pathways are crucial in
      the PDGF-induced VEGF expression in hVSMCs . In this study, we investigated the
      effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the
      PDGF-induced VEGF expression in hVSMCs and the underlying mechanisms. EGCG were
      found to inhibit dose-dependently the VEGF expression and activation of PDGF
      receptor, Erk-1/2 and AP-1 induced by PDGF. In addition, cell free studies
      demonstrated that EGCG could directly inhibit the Erk-1/2 activity. Conditioned
      media from the hVSMCs treated with PDGF could remarkably stimulate the in vitro
      growth of human umbilical vein endothelial cells (HUVECs) but the media from the
      EGCG-pretreated hVSMCs lost its stimulatory activity for HUVEC proliferation.
      These results suggest that EGCG may exert the anti-angiogenic effect by
      inhibiting the PDGF-induced VEGF expression at multiple signaling levels.

PMID- 17016659
TI  - Combination of 5-FU and IFNalpha enhances IFN signaling pathway and caspase-8
      activity, resulting in marked apoptosis in hepatoma cell lines.
AB  - Interferon (IFN) combined with 5-Fluorouracil (5-FU) treatment has recently been
      reported to show beneficial effects in patients with advanced hepatocellular
      carcinoma. IFNalpha is usually provided for this combination therapy. In this
      study, we investigated the molecular mechanisms of apoptosis induction in
      hepatoma cell lines with IFNalpha and 5-FU combination therapy from the view
      point of 5-FU's additive effect on interferon-related signaling pathways. Five
      hepatoma cell lines (Hep3B, Huh7, HLE, PLC/PRF/5, and HepG2) were tested for
      apoptosis inducibility by IFNalpha in the absence or presence of 5-FU. Hep3B was
      the most apoptosis sensitive to IFN plus 5-FU treatment. The JAK/STAT pathway
      transcriptional factor ISRE was activated more synergistically when 5-FU was
      added to IFNalpha treatments. Caspase-3, -9, and especially caspase-8 activity
      was higher with IFN alpha plus 5-FU than IFN or 5-FU alone. Inhibition of caspase
      8, -9, c-Jun N-terminal kinase (JNK), phosphatidylinositide 3-kinase (PI3K), and
      p38 mitogen-activated protein kinase (p38 MAPK) revealed that caspase-8
      inhibition was the most effective at decreasing the apoptotic effects of IFN
      and/or 5-FU. In JAK1 and ISGF3gamma-silenced Hep3B cells, the apoptosis induction
      and caspase-8 activation levels by IFN, even in combination with 5-FU, were
      abrogated. In conclusion, caspase-8 is the most important factor that controls
      IFN and 5-FU-induced apoptosis in hepatoma cell lines.

PMID- 17016660
TI  - Efficient induction of specific cytotoxic T lymphocytes to tumor rejection
      peptide using functional matured 2 day-cultured dendritic cells derived from
      human monocytes.
AB  - Dendritic cells (DCs) are powerful antigen-presenting cells (APCs), that have so
      far been applied for cancer specific immunotherapy. Recent results suggest that
      matured DCs derived from human monocytes have a significant impact on the outcome
      of vaccination. The conventional generation of mature DCs from human monocytes in
      vitro has been reported to require 5 days for differentiation with granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 2 days for
      stimulation. We herein report a new strategy for the functional maturation of
      monocyte-derived DCs within only 2 days of in vitro culture and the induction of
      specific cytotoxic T lymphocytes (CTLs) to tumor rejection peptide. The monocytes
      were incubated for 1 day with GM-CSF and IL-4, followed by activation with a
      bacterial product, OK-432 and prostaglandin E2 (PGE2) for another 1 day (rapid
      DC). Rapid DC expressed mature DC surface markers as well as chemokine receptor 7
      and secreted Th1-type cytokines. The DCs generated in this study mobilized Ca2+
      in response to CCL21/6Ckine and SDF-1, but only marginally did so to Mip-1alpha.
      Moreover, when rapid DC were compared with mature conventional 7-day DCs, they
      were equally potent in inducing specific CTLs in vitro. These results indicate
      that the rapid DC is as effective as the monocyte-derived conventional DCs. The
      rapid DC would be a potentially useful new cancer-specific immunotherapy.

PMID- 17016661
TI  - Chemopreventative strategies targeting the MGMT repair protein: augmented
      expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts
      of several Indian medicinal plants.
AB  - O6-alkylguanines are potent mutagenic, pro-carcinogenic and cytotoxic lesions
      induced by exogenous and endogenous alkylating agents. A facilitated elimination
      of these lesions by increasing the activity of O6-methylguanine-DNA
      methyltransferase (MGMT) is likely to be a beneficial chemoprevention strategy,
      which, however, has not been examined. Because, a marginal enhancement of this
      protein may be adequate for genomic protection, we studied alterations in MGMT
      activity and expression in human peripheral blood lymphocytes and cancer cell
      lines induced by water-soluble and alcohol-soluble constituents of several plants
      with established antioxidant and medicinal properties. Both the ethanolic and
      aqueous extracts from neem (Azadirachta indica), holy basil (Ocimum sanctum),
      winter cherry (Withania somnifera), and oregano (Origanum majorana) increased the
      levels of MGMT protein and its demethylation activity in a time-dependent manner
      with a maximum of 3-fold increase after 72-h treatment. The extracts from
      gooseberry (Emblica officinalis), common basil (Ocimum basilicum), and spearmint
      (Mentha viridis) were relatively less efficient in raising MGMT levels. Increased
      levels of MGMT mRNA accounted at least, in part, for the increased activity of
      the DNA repair protein. The herbal treatments also increased glutathione S
      transferase-pi (GSTP1) expression, albeit to a lesser extent than MGMT. These
      data provide the first evidence for the upregulation of human MGMT by plant
      constituents and raise the possibility of rational dietary approaches for
      attenuating alkylation-induced carcinogenesis. Further, they reveal the putative
      antioxidant responsiveness of the MGMT gene in human cells.

PMID- 17016662
TI  - Induction of apoptosis by the 16-kDa amino-terminal fragment of the insulin-like
      growth factor binding protein 3 in human colonic carcinoma cells.
AB  - The insulin-like growth factor binding protein 3 (IGFBP-3) is the major
      circulating IGF binding protein, its function regulated by proteolytic cleavage.
      The fragments generated have recently been suggested to have IGF-independent
      biological activity. We have previously established that IGFBP-3 can potentiate
      apoptosis in colorectal epithelial cells, although its use as a therapeutic
      reagent may be limited by the fact that it is cleaved in the circulation.
      Therefore the aim of these experiments was to determine whether the 16-kDa
      proteolytic fragment (1-95IGFBP-3) would have IGF-independent pro-apoptotic
      activity in human colonic carcinoma derived cells. We report that the enforced
      expression of 1-95IGFBP-3 increased the induction of apoptosis by the naturally
      occurring short chain fatty acid sodium butyrate (NaBt) in the IGF non-responsive
      HT29 human colorectal carcinoma cell line. Furthermore, the addition of condition
      medium containing the secreted 1-95IGFBP-3 was as effective as the intact IGFBP-3
      protein at potentiating apoptosis. Although not associated with changes in Bcl-2,
      Bcl-XL, Bax, Bad or Bak expression levels, we report that the expression of the
      pro-apoptotic 1-95IGFBP-3 fragment is associated with the inhibition of TNFalpha
      induced NF-kappaB activity, similar to that reported for the full length IGFBP-3
      protein. These results suggest that the 16-kDa 1-95IGFBP-3 fragment is as
      effective as an intact recombinant protein when used in combination with
      apoptosis inducing agents, and due to its relative stability in the circulation,
      it may be important for use as an adjuvant in the treatment of colorectal cancer.

PMID- 17016663
TI  - In vitro cytotoxicity of Phortress against colorectal cancer.
AB  - Phortress is a novel benzothiazole compound with activity concentrated in certain
      breast, ovarian and renal cancer cell lines. Its anti-angiogenic effects are
      unknown. In this study, the in vitro anti-angiogenic effects of Phortress were
      screened for and results compared with two control drugs, paclitaxel and
      fumagillin. in vitro anti-angiogenic activity was examined by MTS assays, growth
      curves and clonogenic survival assays on human umbilical vein endothelial cells
      (HUVEC). In addition and as a comparator, effects were examined on MRCV
      fibroblasts and also the MCF7 breast cancer cell line, shown to be sensitive on
      the NCI60 panel and 3 colorectal cancer cell lines (HT29, SW480 and SW620) that
      were reportedly insensitive. Effects on endothelial tube differentiation were
      assessed by the Matrigel assay. Phortress had no effect on HUVEC and MRCV cell
      proliferation and survival. Unlike paclitaxel and fumagillin, Phortress did not
      inhibit endothelial tube differentiation. Phortress therefore exhibits no in
      vitro anti-angiogenic activity. As expected, Phortress was cytotoxic to MCF7
      breast cancer cells, but unexpectedly, Phortress was also potent against
      colorectal cancer cells in clonogenic survival and cell growth (growth curves but
      not MTS assay) end-points. The efficacy of Phortress against colorectal cancer
      cells in the current study confirms that the spectrum of activity of Phortress
      may be wider than previously thought.

PMID- 17016664
TI  - Corticosteroids induce chemotherapy resistance in the majority of tumour cells
      from bone, brain, breast, cervix, melanoma and neuroblastoma.
AB  - Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co
      medication in cancer therapy because they have potent proapoptotic properties in
      lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy
      tissue. However, GCs are used in a supportive-care role, even though no
      prospective clinical studies have assessed the effect of these steroids on the
      growth of solid tumours. Data from preclinical and, to some extent, clinical
      studies, suggest that GCs induce treatment resistance in some solid tumours.
      Since it is unknown whether GC-induced resistance occurs only occasionally or is
      a more common phenomenon, we performed a screening study using several
      established cell lines from bone, brain, breast and cervix carcinoma as well as
      melanoma and neuroblastoma together with fresh surgical resections from patients
      with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil
      induced apoptosis and promotes the growth of the majority of examined malignant
      cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the
      cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus,
      these data demonstrate the need for detailed molecular studies to clarify the
      mechanism of differential glucocorticoid signaling as well as controlled,
      prospective clinical studies.

PMID- 17016665
TI  - Potential of the Akt inhibitor LY294005 to antagonize the efficacy of Cisplatin
      against HCT116 tumor cells in a DNA mismatch repair-dependent manner.
AB  - Human colorectal adenocarcinoma sublines either deficient (HCT116+ch2) or
      proficient (HCT116+ch3) in the function of MLH1, one of five proteins crucial to
      DNA mismatch repair (MMR), were used to investigate whether the Akt-specific
      inhibitor LY294005 could not only increase the efficacy of platinum drugs in
      HCT116 cells in general but also increase the efficacy of the cisplatinum
      compounds Cisplatin and Lipoplatin specifically in MLH1-deficient, Cisplatin- and
      Lipoplatin-resistant HCT116 cells. We report that, under the conditions it
      increased the efficacy of Docetaxel and did not affect that of 6-thioguanine,
      LY294005 decreased the sensitivity of both sublines to Cisplatin, Lipoplatin,
      Oxaliplatin, and Lipoxal. Notably, the LY294005-imposed decrease was
      significantly higher in the MLH1-proficient than in the MLH1-deficient subline
      with Cisplatin and Lipoplatin, whereas it was nearly the same in both sublines
      with Oxaliplatin and Lipoxal. These LY294005-imposed changes in drug sensitivity,
      i.e. increase with Docetaxel and decreases with platinum compounds, were not
      associated with the concomitant abrogation in the levels of phospho-Aktser473.
      Analogous changes in drug sensitivity were also observed with the PI3-kinase
      inhibitor LY294002, but these changes were associated with complete abrogation of
      phospho-Aktser473. These observations suggest a possible relationship between MMR
      mediated cisplatinum DNA damage signaling and the Akt signaling pathway, e.g. a
      common target for both pathways. A possibly novel property of Akt in aggravating
      drug sensitivity may also be proposed.

PMID- 17016666
TI  - Elevated levels of tumour endothelial marker-8 in human breast cancer and its
      clinical significance.
AB  - Tumour endothelial marker-8 (TEM-8) belongs to a family of endothelial markers
      that are raised during tumour angiogenesis. We have recently reported aberrant
      expression of TEMs at the mRNA level in human breast cancer. This study sought to
      examine the level of TEM-8 expression at the protein and mRNA level in human
      breast cancer tissue, and in a panel of human breast cancer cell lines. We also
      wished to determine if TEM-8 can be used as a suitable marker for identifying
      tumour associated micro-vessels. At the mRNA level more tumours showed positive
      TEM-8 expression compared to normal background tissue. TEM-8 was detected in a
      variety of breast cancer cell lines, endothelial cells (HECV) and in a human
      fibroblast cell line (MRC5) at both the mRNA and protein level. Using
      immunohistochemistry the distribution of TEM-8 staining was more widespread in
      invasive breast cancer tissue compared to normal background tissue. Furthermore,
      the TEM-8 marker was found to be more discriminatory in identifying micro-vessels
      in tumour endothelium (2.8+/-0.83 vs. normal 1.66+/-0.52; P<0.011), compared to
      the vWFA marker (1.61+/-0.54 vs. normal 2.71+/-0.76; P<0.009). Raised levels of
      TEM-8 were associated with shorter survival outcome, but were not correlated to
      disease-free survival as shown by Kaplan-Meier and Cox regression analysis. We
      conclude that TEM-8 is a useful marker for identifying tumour associated micro
      vessels and that elevated levels are associated with disease progression, which
      may have some bearing on the prognostic outcome in breast cancer.

PMID- 17016667
TI  - Survivin promoter-based conditionally replicative adenoviruses target
      cholangiocarcinoma.
AB  - Cholangiocarcinoma is a highly malignant neoplasm with no effective treatment.
      Conditionally replicative adenoviruses (CRAds) represent a promising new modality
      for the treatment of cancer in general. A key contribution in this regard was the
      introduction of tumor-selective viral replication for amplification of the
      initial inoculum in the neoplastic cell population. Under ideal conditions
      following cellular infection, the viruses replicate selectively in the infected
      tumor cells and kill the cells by cytolysis, leaving normal cells unaffected.
      However, to date there have been two limitations to the clinical application of
      these CRAd agents, i.e. poor viral infectivity and tumor specificity. Here we
      report the construction of three new CRAd agents, CRAd-S.RGD, CRAd-S.F5/3 and
      CRAd-S.pk7, in which the tumor specificity is regulated by a tumor-specific
      promoter, the survivin promoter, and the viral infectivity is enhanced by
      incorporating a capsid modification (RGD, F5/3 or pk7) in the adenovirus fiber
      region. These CRAd agents effectively target cholangiocarcinoma cells, induce
      strong cytoxicity in these cells in vitro and inhibit tumor growth in a murine
      xenograft model in vivo. In addition, the survivin promoter has extremely low
      activity both in the non-transformed cell line, HMEC, and in human liver tissue.
      Our results suggest that the survivin-based CRAds are promising agents for
      targeting cholangiocarcinoma with low host toxicity. Such results should provide
      important insights into the identification of novel therapeutic strategies for
      cholangiocarcinoma.

PMID- 17016668
TI  - An automated assignment-free Bayesian approach for accurately identifying proton
      contacts from NOESY data.
AB  - The identification of proton contacts from NOE spectra remains the major
      bottleneck in NMR protein structure calculations. We describe an automated
      assignment-free system for deriving proton contact probabilities from NOESY peak
      lists that can be viewed as a quantitative extension of manual assignment
      techniques. Rather than assigning contacts to NOESY crosspeaks, a rigorous
      Bayesian methodology is used to transform initial proton contact probabilities
      derived from a set of 2992 protein structures into posterior probabilities using
      the observed crosspeaks as evidence. Given a target protein, the Bayesian
      approach is used to derive probabilities for all possible proton contacts. We
      evaluated the accuracy of this approach at predicting proton contacts on 60 (15)N
      separated NOESY and (13)C separated NOESY datasets simulated from experimentally
      determined NMR structures and compared it to CYANA, an established method for
      proton constraint assignment. On average, at the highest confidence level, our
      method accurately identifies 3.16/3.17 long range contacts per residue and
      12.11/12.18 interresidue proton contacts per residue. These accuracies represent
      a significant increase over the performance of CYANA on the same data set. On a
      difficult real dataset that is publicly available, the coverage is lower but our
      method retains its advantage in accuracy over CANDID/CYANA. The algorithm is
      publicly available via the Protinfo NMR webserver
      http://protinfo.compbio.washington.edu/protinfo_nmr .

PMID- 17016669
TI  - NMR assignment of the chitin-binding domain of a hyperthermophilic chitinase from
      Pyrococcus furiosus.

PMID- 17016670
TI  - NMR assignment of the cAMP-binding domain A of the PKA regulatory subunit.

PMID- 17016671
TI  - NMR assignment of domain 3 of the receptor-associated protein (RAP).

PMID- 17016672
TI  - Introduction of the anti-apoptotic baculovirus p35 gene in passion fruit induces
      herbicide tolerance, reduced bacterial lesions, but does not inhibits passion
      fruit woodiness disease progress induced by cowpea aphid-borne mosaic virus
      (CABMV).
AB  - The introduction of anti-apoptotic genes into plants leads to resistance to
      environmental stress and broad-spectrum disease resistance. The anti-apoptotic
      gene (p35) from a baculovirus was introduced into the genome of passion fruit
      plants by biobalistics. Eleven regenerated plants showed the presence of the p35
      gene by PCR and/or dot blot hybridization. Transcriptional analysis of
      regenerated plants showed the presence of specific p35 transcripts in 9 of them.
      Regenerated plants containing the p35 gene were inoculated with the cowpea aphid
      borne mosaic virus (CABMV), the bacterium Xanthomonas axonopodis pv passiflorae,
      and the herbicide, glufosinate, (Syngenta). None of the plants showed resistance
      to CABMV. Regenerated plants (p35+) showed less than half of local lesions showed
      by non-transgenic plants when inoculated with X. axonopodis and some p35+ plants
      showed increased tolerance to the glufosinate herbicide when compared to non
      transgenic plants.

PMID- 17016674
TI  - Detection of aromatic catabolic gene expression in heterogeneous organic matter
      used for reduction of volatile organic compounds (VOC) by biofiltration.
AB  - A qualitative procedure of purified DNA/RNA co-extraction from complex organic
      matter, used as biofilter support for removing volatile organic compounds, was
      set up and applied to detect xylene monooxygenase gene expression by RT-PCR. A
      DNA/RNA extraction protocol based on a combination of sample lyophilization pre
      treatment and CTAB--phenol/chloroform extraction procedure was optimized for the
      recovery of purified nucleic acids [100-500 ng DNA (10 kb) and 0.5-2 microg of
      rRNA 16S from 100 mg matrix]. PCR and RT-PCR protocols were established to detect
      xylene monooxygenase gene expression starting from differentially induced organic
      matrices obtained by biofiltration technology. This work allowed the microbial
      degradation activities in heterogeneous organic solid media to be studied and
      suggests a rapid method to follow specific biological activities during solid
      and/or semisolid organic substrates biotransformation.

PMID- 17016673
TI  - Expression of a carbonic anhydrase gene is induced by environmental stresses in
      rice (Oryza sativa L.).
AB  - Expression of the gene (OsCA1) coding for carbonic anhydrase (CA) in leaves and
      roots of rice was induced by environmental stresses from salts (NaCl, NaHCO(3)
      and Na(2)CO(3)), and osmotic stress (10%, w/v, PEG 6000). CA activity of rice
      seedlings more than doubled under some of these stresses. Transgenic Arabidopsis
      over-expressing OsCA1 had a greater salt tolerance at the seedling stage than
      wild-type plants in 1/2 MS medium with 5 mM NaHCO(3), 50 mM NaCl, on 100 mM NaCl.
      Thus CA expression responds to environmental stresses and is related to stress
      tolerance in rice.

PMID- 17016675
TI  - Analysis of the evolution of the thrombin-inhibiting DNA aptamers using a genetic
      algorithm.
AB  - We previously identified a thrombin-inhibiting DNA aptamer that was presumed to
      form a G-quartet structure with a duplex. To investigate the importance of the
      sequences in the duplex region and to obtain aptamers with higher inhibitory
      activities, we randomized the sequences of the duplex region of this aptamer and
      carried out selection based on inhibitory activity using a genetic algorithm.
      This method consisted of selection via an inhibition assay, crossover, and
      mutation in silico. After two cycles, we obtained ligands with greater inhibitory
      activities than that of the original aptamer. In addition, the duplex sequences
      were found to contribute to the inhibitory activities of aptamers.

PMID- 17016676
TI  - Differential role of PI3K/Akt pathway in the infarct size limitation and
      antiarrhythmic protection in the rat heart.
AB  - Endogenous cardiac protection against prolonged ischemic insult can be achieved
      by repeated brief episodes of ischemia (hypoxia) or by cardiac adaptation to
      various stresses such as chronic hypoxia. Activation of phosphatidylinositol 3
      kinase (PI3K)/Akt is involved in antiapoptotic effects, however, it is not clear
      whether it is required for overall heart salvage including protection against
      myocardial infarction and arrhythmias. We focussed on the potential common role
      of PI3K/Akt in anti-infarct protection, in the experimental settings of long-term
      adaptation to chronic intermittent hypobaric hypoxia (IHH; 8 h/day, 25-30
      exposures, in vivo rats) and acute ischemic preconditioning (IP; Langendorff
      perfused hearts). In addition, we explored the role of PI3K/Akt in susceptibility
      to ischemic ventricular arrhythmias. In normoxic open-chest rats, PI3K/Akt
      inhibitor LY294002 (LY; 0.3 mg/kg) given 5 min before test occlusion/reperfusion
      (I/R) did not affect infarct size (IS) normalized to the size of area at risk
      (AR). In hypoxic rats, LY partially attenuated IS-limiting effect of IHH (IS/AR
      59.7 +/- 4.1% vs. 51.8 +/- 4.4% in the non-treated rats; p > 0.05) and increased
      IS/AR to its value in normoxic rats (64.9 +/- 5.1%). In the isolated hearts, LY
      (5 muM) applied 15 min prior to I/R completely abolished anti-infarct protection
      by IP (IS/AR 55.0 +/- 4.9% vs. 15.2 +/- 1.2% in the non-treated hearts and 42.0
      +/- 5.5% in the non-preconditioned controls; p < 0.05). In the non-preconditioned
      hearts, PI3K/Akt inhibition did not modify IS/AR, on the other hand, it markedly
      suppressed arrhythmias. In the LY-treated isolated hearts, the total number of
      ventricular premature beats and the incidence of ventricular tachycardia (VT) was
      reduced from 518 +/- 71 and 100% in the controls to 155 +/- 15 and 12.5%,
      respectively (p < 0.05). Moreover, bracketing of IP with LY did not reverse
      antiarrhythmic effect of IP. These results suggest that activation of PI3K/Akt
      cascade plays a role in the IS-limiting mechanism in the rat heart, however, it
      is not involved in the mechanisms of antiarrhythmic protection.

PMID- 17016677
TI  - Describing the sensory abnormalities of children and adults with autism.
AB  - Patterns of sensory abnormalities in children and adults with autism were
      examined using the Diagnostic Interview for Social and Communication Disorders
      (DISCO). This interview elicits detailed information about responsiveness to a
      wide range of sensory stimuli. Study 1 showed that over 90% of children with
      autism had sensory abnormalities and had sensory symptoms in multiple sensory
      domains. Group differences between children with autism and clinical comparison
      children were found in the total number of symptoms and in specific domains of
      smell/taste and vision. Study 2 confirmed that sensory abnormalities are
      pervasive and multimodal and persistent across age and ability in children and
      adults with autism. Age and IQ level affects some sensory symptoms however.
      Clinical and research implications are discussed.

PMID- 17016679
TI  - Diagnosis of tachycardia mechanism with cryomapping in a toddler with complex
      congenital heart disease.
AB  - A 2.5-year-old patient with complex congenital heart disease involving
      dextrocardia, atrioventricular and ventriculoarterial discordance, pulmonary
      stenosis, ventricular septal defect (VSD), atrial septal defect (ASD), and
      paroxysmal supraventricular tachycardia (SVT) underwent electrophysiological
      study. The tachycardia mechanism was diagnosed with cryomapping. The ability of
      cryomapping to have transient and reversible effect on the tissue, unlike
      radiofrequency (RF) ablation, helped in the establishment of diagnosis in this
      toddler with typical atrioventricular nodal reentrant tachycardia. Cryomapping
      can be an additional safe diagnostic utility in young patients with complex
      congenital heart disease.

PMID- 17016678
TI  - Neuropsychological functioning of siblings of children with autism, siblings of
      children with developmental language delay, and siblings of children with mental
      retardation of unknown genetic etiology.
AB  - Neuropsychological functioning of 30 siblings of children with autism (AU-S), 28
      siblings of children with mental retardation of (MR-S), and 30 siblings of
      children with developmental language delay (DLD-S) was compared. Two siblings,
      both AU-S, received diagnoses of pervasive developmental disorder (PDD). More
      siblings with cognitive disabilities were found in DLD-S than in AU-S. However,
      these differences disappeared after excluding diagnosed siblings or after
      accounting for family membership. In sum, despite the elevated incidence of PDD
      among AU-S, the neuropsychological functioning of the remaining siblings did not
      convey specific characteristics related to the genetic risk associated with
      autism, in contrast to the cognitive functioning of the DLD-S, which did reflect
      a genetic risk.

PMID- 17016680
TI  - Remote-controlled magnetic ablation of a right anterolateral accessory pathway -
      the superior caval vein approach.
AB  - OBJECTIVE: An 18-year old male patient with recurrent supraventricular
      tachycardias was admitted for catheter ablation. Baseline ECG was consistent with
      right anterolateral accessory pathway (AP) conduction. MATERIALS AND METHODS: The
      novel magnetic navigation system (MNS, Niobe Stereotaxis) in combination with a
      catheter advancer unit (Cardiodrive, Stereotaxis) allows a complete remote
      controlled electrophysiologic study and ablation. RESULTS: Despite accurate
      identification of the AP insertion site using the MNS, a stable catheter position
      was not achieved from the inferior caval vein. Therefore, the venous access was
      switched to the superior caval vein approach using the left subclavian vein. The
      same magnetic field vector now resulted in a perfectly stable catheter position,
      and application of radiofrequency current immediately blocked AP conduction.
      CONCLUSION: This case demonstrates feasibility and safety of a complete remote
      controlled ablation of a right-sided anterolateral accessory pathway using the
      superior approach in conjunction with the novel magnetic navigation system Niobe.

PMID- 17016681
TI  - Dual mechanisms underlying pulmonary vein tachycardias in a patient with
      paroxysmal atrial fibrillation.
AB  - We report a case of a 46-year-old man with paroxysmal atrial fibrillation who
      underwent pulmonary vein isolation. After a complete isolation of each pulmonary
      vein was performed, two different types of pulmonary vein tachycardia appeared: a
      regular tachycardia in the left inferior pulmonary vein with a supposed reentrant
      mechanism, and an irregular tachycardia in the right superior PV showing a
      nonreentrant character.

PMID- 17016682
TI  - Direct comparison of computed tomography and magnetic resonance imaging for
      characterization of posterior left atrial morphology.
AB  - OBJECTIVE: Accumulating evidence points to the central importance of the
      posterior left atrium (PLA) for atrial fibrillation (AF). Catheter ablation
      intended to cure AF is increasingly practiced; performance and assessment of this
      procedure is enhanced by accurate imaging of PLA anatomy. Prior reports have
      suggested that both computed tomographic (CT) and magnetic resonance (MR) imaging
      techniques provide accurate PLA images. These techniques have never been compared
      directly. MATERIALS AND METHODS: Twenty patients referred for catheter ablation
      underwent preoperative imaging using both CT and MR. Each technique was used to
      create a multidimensional image of the PLA. RESULTS: Within patients, morphologic
      and dimensional PLA indices, including number of individual pulmonary venoatrial
      junctions, presence of ostial branches, circumference of each venoatrial
      junction, venoatrial junction "non-circularity", and distance between ipsilateral
      superior and inferior venoatrial junctions, were well correlated. CONCLUSIONS: CT
      and MR-based images of the PLA appear comparable. Technique selection should
      involve considerations of toxicity, tolerance, and local resources.

PMID- 17016683
TI  - Case report: Delayed detection of ventricular tachycardia due to intradevice
      interactions by implantable atrio-ventricular pacer/cardioverter defibrillator.
AB  - Current generations of implantable cardioverter defibrillators are capable of
      providing sophisticated dual chamber atrioventricular and rate-responsive pacing
      therapies, and even cardiac resynchronization therapy. Appropriate programming of
      the devices is necessary for them to perform all such sophisticated tasks. In
      this report, we describe a case where detection of ventricular tachycardia was
      delayed due to intradevice interactions between the pacemaker and defibrillator
      components of the device.

PMID- 17016684
TI  - Chronic migraine prevention with topiramate.
AB  - Chronic migraine (CM) is a disabling condition with not many treatment strategies
      available. Topiramate is effective in episodic migraine prevention, however
      little is known about its effect in CM. An open label study was performed. Sixty
      four patients diagnosed with CM or probable CM according to the IHS diagnostic
      criteria were enrolled, 50 patients were available for analysis and an intention
      to-treat methodology was applied. The primary endpoint considered was the number
      of patients with a decrease in headache frequency higher than 50%. The median
      dose was 100 mg, a reduction in frequency higher than 50% occurred in 33 patients
      (66%) and 14 (28%) presented a complete response, defined as a frequency
      reduction higher than 95%. The medication was well tolerated. The most common
      side effects found were weight loss, paraesthesias, nausea, cognitive
      dysfunction, fatigue, somnolence, insomnia and depression. Our findings suggest
      that topiramate is effective in CM prophylaxis.

PMID- 17016685
TI  - Dental microwear in relation to changes in the direction of mastication during
      the evolution of Myodonta (Rodentia, Mammalia).
AB  - Observations of dental microwear are used to analyse the correlation between
      changes in molar tooth crown morphology and the direction of masticatory movement
      during the evolution of Myodonta (Rodentia, Mammalia). The studied sample
      includes 36 specimens representing both superfamilies of Myodonta (Muroidea and
      Dipodoidea) spanning 16 dipodoid and 9 muroid species. Microscopic scratches on
      occlusal surfaces resulting from contact between opposite teeth during
      mastication are analysed. Using these features, we determine the direction of
      masticatory movements. Microwear patterns display diverse orientations among
      Dipodoidea: oblique in Sicistinae, Euchoreutinae and Zapodinae, propalinal in
      Dipodinae and intermediary in Allactaginae. Similarly, Muroidea exhibit the
      following orientations: oblique in Cricetinae and propalinal in Arvicolinae,
      Cricetomyinae, Gerbillinae and Murinae. These various chewing types illustrate
      different evolutionary grades within the superfamilies. Acquisition of the antero
      posterior masticatory movement in Dipodoidea is related to flattening of the
      molar occlusal surface. However, in some muroid subfamilies, this direction of
      mastication is associated with low-crowned and cuspidate molars (Cricetomyinae,
      Murinae).

PMID- 17016686
TI  - A previously unrecognized group of Middle Jurassic triconodontan mammals from
      Central Asia.
AB  - Ferganodon narynensis gen. et sp. nov. is represented by a lower molariform tooth
      from the Middle Jurassic (Callovian) Balabansai Svita in Kyrgyzstan. The new
      genus is allied with Klamelia zhaopengi Chow and Rich 1984 from the Middle
      Jurassic Shishugou Formation in Xinjiang, northwest China to the new family
      Klameliidae based on parallelogram-shaped lower molariforms, imbricating rather
      than interlocking of cusps e-d-f, by a peculiar distolabial cingulid cusp, and by
      vertical folding of the enamel on the labial crown side. The new family
      Klameliidae fam. nov. is most similar to Gobiconodontidae by the structure of the
      molariform teeth and represents a previously unrecognized radiation of
      eutriconodontan mammals possibly endemic to Central Asia.

PMID- 17016687
TI  - Molecular cytogenetic analyses of hexaploid lines spontaneously appearing in
      octoploid Triticale.
AB  - Genome characterization of 14 hexaploid lines that spontaneously appeared in
      octoploid Triticales was carried out by sequential genomic in situ hybridization
      and fluorescence in situ hybridization, high molecular weight glutenin subunits
      and SSR marker analyses. All of the lines showed a chromosome constitution of
      complete A and B genomes, and a composite genome consisting of the chromosomes of
      D and R genomes. The composite genome of the 11 lines consisted of chromosomes
      1R, 2D, 3R, 4R, 5R, 6R and 7R, that of the two lines were 1D, 2D, 3R, 4R, 5R, 6R
      and 7R, and that of one line was 1R, 2D, 3R, 4R, 5R, 6D and 7R. The
      incompatibility of the D and R genomes in common wheat genetic background,
      preferential retention of chromosome 2D and importance of these lines for the
      development of hexaploid Triticale are discussed in this report.

PMID- 17016688
TI  - Comparative sequence and genetic analyses of asparagus BACs reveal no
      microsynteny with onion or rice.
AB  - The Poales (includes the grasses) and Asparagales [includes onion (Allium cepa
      L.) and asparagus (Asparagus officinalis L.)] are the two most economically
      important monocot orders. The Poales are a member of the commelinoid monocots, a
      group of orders sister to the Asparagales. Comparative genomic analyses have
      revealed a high degree of synteny among the grasses; however, it is not known if
      this synteny extends to other major monocot groups such as the Asparagales.
      Although we previously reported no evidence for synteny at the recombinational
      level between onion and rice, microsynteny may exist across shorter genomic
      regions in the grasses and Asparagales. We sequenced nine asparagus BACs to
      reveal physically linked genic-like sequences and determined their most similar
      positions in the onion and rice genomes. Four of the asparagus BACs were selected
      using molecular markers tightly linked to the sex-determining M locus on
      chromosome 5 of asparagus. These BACs possessed only two putative coding regions
      and had long tracts of degenerated retroviral elements and transposons. Five
      asparagus BACs were selected after hybridization of three onion cDNAs that mapped
      to three different onion chromosomes. Genic-like sequences that were physically
      linked on the cDNA-selected BACs or genetically linked on the M-linked BACs
      showed significant similarities (e < -20) to expressed sequences on different
      rice chromosomes, revealing no evidence for microsynteny between asparagus and
      rice across these regions. Genic-like sequences that were linked in asparagus
      were used to identify highly similar (e < -20) expressed sequence tags (ESTs) of
      onion. These onion ESTs mapped to different onion chromosomes and no relationship
      was observed between physical or genetic linkages in asparagus and genetic
      linkages in onion. These results further indicate that synteny among grass
      genomes does not extend to a sister order in the monocots and that asparagus may
      not be an appropriate smaller genome model for plants in the Asparagales with
      enormous nuclear genomes.

PMID- 17016689
TI  - Mapping quantitative trait loci in chickpea associated with time to flowering and
      resistance to Didymella rabiei the causal agent of Ascochyta blight.
AB  - Drought is the major constraint to chickpea (Cicer arietinum L.) productivity
      worldwide. Utilizing early-flowering genotypes and advancing sowing from spring
      to autumn have been suggested as strategies for drought avoidance. However,
      Ascochyta blight (causal agent: Didymella rabiei (Kov.) v. Arx.) is a major
      limitation for chickpea winter cultivation. Most efforts to introgress resistance
      to the pathogen into Kabuli germplasm resulted in relatively late flowering
      germplasm. With the aim to explore the feasibility of combining earliness and
      resistance, RILs derived from a cross between a Kabuli cultivar and a Desi
      accession were evaluated under field conditions and genotyped with SSR markers.
      Three quantitative trait loci (QTLs) with significant effects on resistance were
      identified: two linked loci located on LG4 in epistatic interaction and a third
      locus on LG8. Two QTLs were detected for time to flowering: one in LG1 and
      another on LG2. When resistance and time to flowering were analyzed together, the
      significance of the resistance estimates obtained for the LG8 locus increased and
      the locus effect on days to flowering, previously undetected, was significantly
      different from zero. The identification of a locus linked both to resistance and
      time to flowering may account for the correlation observed between these traits
      in this and other breeding attempts.

PMID- 17016690
TI  - Hypermethylation of Cyclin D2 is associated with loss of mRNA expression and
      tumor development in prostate cancer.
AB  - D-type cyclins play a pivotal role in cell cycle regulation and their abnormal
      expression was associated with several human malignancies. To assess Cyclin D2
      promoter methylation status and expression levels in prostate tissues,
      quantitative methylation-specific PCR and quantitative reverse transcription PCR
      assays were performed in a large series of prostate carcinomas, high-grade
      prostatic intraepithelial neoplasias (HGPIN), benign prostate hyperplasias (BPH),
      normal prostate tissue (NPT) samples, and prostate cancer (PCa) cell lines
      (before and after demethylating treatment). Methylation levels were correlated
      with mRNA expression levels and key clinicopathologic parameters. Cyclin D2
      promoter methylation was found in 117/118 PCa, 38/38 HGPIN, 24/30 BPH, 11/11 NPT,
      and 4/4 cell lines. Methylation levels were significantly higher in PCa compared
      with HGPIN, NPT, and BPH (P<0.0001), correlating with tumor stage and Gleason
      score (r=0.29, P=0.0014; and r=0.32, P=0.0005, respectively). Conversely, Cyclin
      D2 mRNA levels were significantly lower in PCa (P<0.01) and a significant inverse
      correlation between Cyclin D2 methylation and expression levels was found in
      prostatic tissues (r=-0.61, P<0.000001). Demethylating treatment induced a
      substantial increase in Cyclin D2 mRNA in LNCaP cells whereas decreased levels
      were observed in DU-145 and PC-3 cells. We concluded that Cyclin D2 promoter
      methylation downregulates gene transcription and occurs with high frequency at
      low levels in normal, hyperplastic, and preneoplastic prostate tissues.
      Conversely, high Cyclin D2 methylation levels characterize invasive prostatic
      carcinoma, correlating with clinicopathologic features of tumor aggressiveness.

PMID- 17016691
TI  - Upstream transcription factor 1 gene polymorphisms are associated with high
      antilipolytic insulin sensitivity and show gene-gene interactions.
AB  - Upstream transcription factor 1 (USF1) regulates the expression of many genes
      involved in lipid and glucose metabolism, among them genes regulating lipolysis.
      USF1 specifically regulates the expression of the hormone-sensitive lipase gene
      (HSL) in adipocytes and the hepatic lipase gene (LIPC) in the liver, which was
      found to be involved in liver fat accumulation. The usf1s1 C > T and usf1s2 G > A
      single-nucleotide polymorphisms (SNPs) in USF1 are associated with increased in
      vitro catecholamine-induced lipolysis in adipocytes. We investigated first
      whether SNPs in USF1 affect the lipolysis-suppressing action of insulin in vivo,
      and second, whether they interact with the -60C > G SNP in HSL on lipolysis and
      the -514C > T SNP in LIPC on liver fat. The usf1s1 C > T and usf1s2 G > A SNPs,
      together with the SNPs in HSL and LIPC, were determined in 407 Caucasians.
      Lipolysis was estimated as a change in free fatty acid (FFA) levels from baseline
      to 2 h of a 75-g oral glucose tolerance test (OGTT). Fifty-four subjects had data
      from a euglycemic hyperinsulinemic clamp with calculation of antilipolytic
      insulin sensitivity. Subjects carrying the minor alleles (T of usf1s1 and A of
      usf1s2) had lower 2 h FFA (p = 0.01) and a larger decrease in FFA concentrations
      during the OGTT (p = 0.02). Antilipolytic insulin sensitivity was higher in these
      individuals (p = 0.03). No interaction of the usf1s1 C > T and usf1s2 G > A SNPs
      with the -60C > G SNP in HSL on antilipolytic insulin sensitivity was detected.
      Liver fat, measured by (1)H magnetic resonance spectroscopy, was elevated only in
      subjects who were both homozygous for the major alleles of usf1s1 and usf1s2 and
      carriers of the T allele of the -514C > T SNP in LIPC (p = 0.01). In conclusion,
      subjects carrying the T allele of SNP usf1s1 and the A allele of SNP usf1s2 have
      a higher antilipolytic insulin sensitivity. Moreover, both SNPs may interact with
      the -514C > T SNP in LIPC to determine liver fat.

PMID- 17016692
TI  - Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA
      specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA
      positive tumor cells.
AB  - Dendritic cells (DC)-derived or tumor-derived exosomes are a population of
      nanometer sized membrane vesicles that can induce specific anti-tumor immunity.
      However, the immunogenic potential and efficiency of exosomes-based tumor vaccine
      are not satisfactory enough to achieve a curative effect in clinical trials. In
      this article we investigated whether IL-18 genetic modification of tumor cells
      can increase the efficacy of exosomes derived from IL-18 gene-modified tumor
      cells. We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with
      a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the
      exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells. We found that Exo/IL
      18 naturally contain CEA and bioactive IL-18. Moreover, Exo-IL-18 are potent in
      chemoattracting DC and T cells, enhancing the proliferation and Th1 cytokine
      release of PBMC, and promoting the phenotypic and functional maturation of DC.
      Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201
      restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer
      patients in vitro. In almost all of these experiments, Exo/IL-18 show more potent
      functions than the conventionally prepared exosomes derived from parent tumor
      cells without IL-18 gene modification. Our findings suggest that Exo/IL-18 has
      more potent capability to induce specific anti-tumor immunity, and our strategy
      of IL-18 modification of exosomes is a feasible approach to develop exosomes
      based tumor vaccines.

PMID- 17016693
TI  - The associations of birthweight, gestational age and childhood BMI with type 2
      diabetes: findings from the Aberdeen Children of the 1950s cohort.
AB  - AIMS/HYPOTHESIS: The aim of this study was to examine the associations of
      birthweight, gestational age and childhood BMI (assessed at a mean age of 5
      years) with a self-report of a doctor diagnosis of diabetes in middle age.
      METHODS: We studied a birth cohort of 5,793 individuals who were born between
      1950 and 1956 in Aberdeen, Scotland, and who responded to a questionnaire
      administered in 2000. RESULTS: Birthweight and gestational age were inversely
      associated with diabetes. These associations remained with additional adjustment
      for indicators of childhood and adult socioeconomic position, maternal
      complications of pregnancy, adult smoking, adult BMI and simultaneous adjustment
      for each other: the adjusted odds ratio per unit increase in birthweight z score
      was 0.73 (95% CI 0.60-0.88), the odds ratio per week increase in gestational age
      was 0.91 (95% CI 0.82-1.00) and odds ratio for preterm birth was 2.04 (94% CI
      1.18-3.53). The positive association of childhood BMI with diabetes was
      attenuated on adjustment for adult BMI. CONCLUSIONS/INTERPRETATION: In this
      population, who were born in the 1950s, poor intrauterine growth and preterm
      birth are associated with an increased risk of diabetes.

PMID- 17016694
TI  - Phosphatidylinositol 3-kinase p85alpha regulatory subunit gene PIK3R1 haplotype
      is associated with body fat and serum leptin in a female twin population.
AB  - AIMS/HYPOTHESIS: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and
      insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2.
      Hence, defective activation of PI3K could be a novel mechanism of peripheral
      leptin or insulin resistance. We investigated associations of tagging single
      nucleotide polymorphisms (tSNPs) in the PI3K p85alpha regulatory subunit gene
      PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female
      twin population of European extraction. MATERIALS AND METHODS: Eight tSNPs were
      genotyped in 2,778 women (mean age 47.4+/-12.5 years) from the St Thomas' UK
      Adult Twin Registry (Twins UK). RESULTS: SNP rs1550805 was associated with serum
      leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat
      percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and
      central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated
      with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and
      central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with
      fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT
      (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%)
      showed higher serum leptin concentration (p=0.007) and body fat measures (p< or
      =0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher
      fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with
      subjects with the most common haplotype, 111 (frequency 45.5%).
      CONCLUSIONS/INTERPRETATION: Association of the PIK3R1 SNP rs1550805 with serum
      leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1
      or IRS2 in response to leptin.

PMID- 17016695
TI  - Increased islet beta cell replication adjacent to intrapancreatic gastrinomas in
      humans.
AB  - AIMS/HYPOTHESIS: Type 1 and type 2 diabetes are characterised by a beta cell
      deficit. Islet hyperplasia has been described in patients with Zollinger-Ellison
      syndrome secondary to gastrin-producing tumours (gastrinomas), and gastrin
      therapy has increased beta cell mass in rodents and human islets in vitro. In the
      present studies we addressed the following questions: (1) In pancreas specimens
      from gastrinoma cases, is the fractional beta cell area increased? (2) If so, is
      this restricted to tumour-adjacent islets or also present in tumour-distant
      islets? (3) Is new beta cell formation (beta cell replication and islet
      neogenesis) increased and beta cell apoptosis decreased in pancreas specimens
      from gastrinoma cases? METHODS: Pancreas was obtained at surgery from four
      patients with Zollinger-Ellison syndrome caused by pancreatic gastrinomas and 15
      control subjects at autopsy. RESULTS: Islet fractional beta cell area (p<0.001),
      islet size (p<0.001) and beta cell replication (Ki67 staining) (p<0.05) were
      increased in islets adjacent to the tumours, but not in tumour-distant pancreas,
      compared with control subjects. We did not observe any differences in beta cell
      apoptosis or in the number of insulin-positive cells in ducts either adjacent to
      or distant from the tumour. CONCLUSIONS/INTERPRETATION: One or more factors
      released by human gastrinomas increase beta cell replication in islets
      immediately adjacent to the tumour, but not in tumour-distant islets. While these
      findings demonstrate that adult human beta cells can be driven into the cell
      cycle, they caution against the therapeutic usefulness of gastrin, since islets
      located >1 cm away from the gastrinomas did not exhibit changes in beta cell
      turnover, despite markedly elevated systemic gastrin levels sufficient to cause
      severe gastrointestinal symptoms.

PMID- 17016698
TI  - Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case
      presenting with semantic dementia and upper motor neuron signs with a clinical
      course of 19 years.
AB  - We report a case of a right-handed 74-year-old man who showed semantic dementia
      with a disease duration of 19 years. He initially presented with excessive use of
      pronouns and semantic paraphasia at the age of 55 years. Impairment of object
      recognition developed 5 years after the onset. Face recognition impairment and
      stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years
      before death. Pathological examination disclosed circumscribed severe atrophy in
      not only the bilateral temporal tips but also in the left precentral gyrus and
      pars opercularis in a motor speech field. Pyramidal tract involvement and loss of
      Betz cells were also evident. On the other hand, neurons in the anterior horns
      and hypoglossal nuclei were spared in number, although astrocytes were mildly
      proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and
      frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were
      present. These features clinically fit the international diagnostic criteria of
      semantic dementia and, histopathologically, frontotemporal lobar degeneration
      with motor neuron disease (FTLD-MND). This case suggests that (1) the
      distribution of cortical lesions associated with language disturbance is not
      uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin
      pathology develop semantic dementia despite the high incidence of language
      disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND.
      After reviewing previous cases of FTLD-MND with a clinical course of more than 10
      years, we also noticed that (3) FTLD-MND cases with a long disease duration often
      show upper motor neuron-predominant involvement.

PMID- 17016696
TI  - Global myocardial perfusion and diastolic function are impaired to a similar
      extent in patients with type 2 diabetes mellitus and in patients with coronary
      artery disease--evaluation by contrast echocardiography and pulsed tissue
      Doppler.
AB  - AIMS/HYPOTHESIS: Using modern echocardiography, we quantified the extent of
      global myocardial function and perfusion abnormalities in patients with type 2
      diabetes and compared this with the hypothetically similar extent of impairments
      in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: This case
      control study (66 patients) compared four age-matched groups: control, type 2
      diabetic, CAD, and diabetic subjects with CAD (DCAD) and left ventricular
      ejection fraction >50%. CAD patients had 1-2 vessel disease. Diastolic and
      systolic myocardial velocities were assessed with pulsed tissue Doppler. Global
      myocardial perfusion was assessed with contrast echocardiography as indices of
      capillary blood volume and myocardial blood flow at maximal vasodilatation. In
      CAD and DCAD patients, functional and perfusion parameters were additionally
      assessed in the territory with a normal coronary angiogram reading, providing a
      model for comparison with the global data from control and diabetic patients.
      RESULTS: Comparing diabetic with control subjects, myocardial velocity at early
      diastole was impaired (8.8+/-1.8 vs 10.1+/-1.7 cm/s; p=0.02) and correlated
      inversely with age, HbA(1c) and pulse pressure (R (2)=0.761). Capillary blood
      volume (16.6+/-5.0 vs 24.4+/-4.9%) and blood flow (56+/-35 vs 114+/-40) were
      decreased (p=0.001). In CAD patients, myocardial velocity at early diastole was
      similarly decreased (p=0.02). CAD and DCAD patients were receiving more
      cardiovascular preventive therapy for the same extent of impaired global
      perfusion as in the less extensively treated diabetes group without CAD
      (p<0.002), but had superior perfusion of the 'normal' coronary territory than
      that group (p<0.05). CONCLUSIONS/INTERPRETATION: In patients with diabetes,
      global diastolic function and myocardial capillary blood volume and blood flow
      are impaired to the same extent as in patients with CAD. These impairments could
      form the basis of new therapeutic concepts.

PMID- 17016699
TI  - Evolution of the CT imaging findings of accessory spleen infarction.
AB  - We report the case of a 12-year-old girl presenting with multiple episodes of
      left upper-quadrant pain caused by torsion of an accessory spleen.We present the
      CT findings of progression of accessory spleen infarction over the course of 7
      days.

PMID- 17016700
TI  - Central venous cannulation: are routine chest radiographs necessary after B-mode
      and colour Doppler sonography check?
AB  - BACKGROUND: After the insertion of a central venous catheter, a chest radiograph
      is usually obtained to ensure correct positioning of the catheter tip. OBJECTIVE:
      To determine in a paediatric population whether B-mode and colour Doppler
      sonography after central venous access is useful to evaluate catheter position,
      thus obviating the need for a postprocedural radiograph. MATERIALS AND METHODS: A
      prospective study of 107 consecutive central venous access procedures placed in a
      paediatric intensive care unit was performed. At the end of the procedure, B-mode
      and colour Doppler sonography were used to assess catheter position and check for
      complications. A postprocedural chest radiograph was obtained in all patients.
      RESULTS: In 96 patients postprocedural B-mode and colour Doppler sonography
      showed colour Doppler signals within the vena cava. Among the 11 patients
      predicted to have a potential complication, there was one pneumothorax and ten
      malpositions. Chest radiography showed a total of 13 complications-1 pneumothorax
      and 12 malpositions. The concordance between colour Doppler sonography and chest
      radiography was 98.1% in the detection of catheter position; sonography had a
      sensitivity of 84.6% and a specificity of 100%. CONCLUSIONS: The close
      concordance between B-mode and colour Doppler sonography and chest radiography
      justifies the more frequent use of sonography to evaluate catheter position
      because ionizing radiation is eliminated. Chest radiography may then be performed
      only when there is suspected inappropriate catheter tip position after
      sonography.

PMID- 17016701
TI  - Reliability of a cycling time trial in a glycogen-depleted state.
AB  - The aim of this study was to investigate the reliability of a protocol designed
      to simulate endurance performance in events of long duration (approximately 5 h)
      where endogenous carbohydrate stores are low. Seven male subjects were recruited
      (age 27 +/- 7 years, VO(2max) 66 +/- 5 ml/kg/min, W (max) 367 +/- 42 W). The
      subjects underwent three trials to determine the reliability of the protocol. For
      each trial subjects entered the laboratory in the evening to undergo a glycogen
      depleting exercise trial lasting approximately 2.5 h. The subjects returned the
      following morning in a fasted state to undertake a 1-h steady-state ride at 50% W
      (max) followed by a time trial of approximately 40-min duration. Each trial was
      separated by 7-14 days. The trials were analysed for reliability of time to
      completion of the time trial using a coefficient of variation (CV), with 95%
      confidence intervals (data are mean +/- SD). The times to complete the three
      trials were 2,546 +/- 529, 2,585 +/- 490 and 2,568 +/- 555 s for trials 1, 2 and
      3, respectively. The CV between trials 1 and 2 was 4.5% (95% CI 2.9-10.4%) and
      between trials 2 and 3, 3.8% (95% CI 2.4-9.9%). There was no difference in oxygen
      uptake, respiratory exchange ratio, carbohydrate oxidation, fat oxidation, plasma
      glucose concentration and plasma lactate concentration between the three trials.
      Therefore we can conclude that prior glycogen depletion does produce a reliable
      measure of performance with metabolic characteristics similar to ultraendurance
      exercise.

PMID- 17016702
TI  - Effect of regular exercise on homocysteine concentrations: the HERITAGE Family
      Study.
AB  - We investigated whether regular aerobic exercise could affect plasma total
      homocysteine (tHcy), and whether there were sex-related or racial differences in
      tHcy changes. Data were available for 816 black and white men and women, aged 17
      65 years, 711 of whom completed a 20 week aerobic exercise training program. The
      tHcy concentration was measured in frozen plasma samples by an HPLC method. In
      Blacks, tHcy did not change with exercise training [men -0.5 (SD 3.7) micromol/l,
      women 0.0 (2.2) micromol/l) but increased significantly in Whites (men +0.3 (1.7)
      micromol/l, women +0.2 (1.6) micromol/l). No sex-related differences were found
      in either racial group. Changes in tHcy correlated negatively with baseline
      homocysteine (r = -0.40, P < 0.0001). Homocysteine levels of the "High"
      (hyperhomocysteinemia) (>or=15 micromol/l) group (n = 30) decreased significantly
      with regular aerobic exercise from 23.1 (12.1) to 19.6 (7.6) micromol/l.
      Homocysteine levels of the "Normal" group increased slightly from 8.2 +/- 2.2 to
      8.5 +/- 2.4 micromol/l. Men exhibit racial differences for tHcy responses to
      exercise training. Regular aerobic exercise has favorable effects on individuals
      with hyperhomocysteinemia, but tHcy slightly increased in individuals within the
      normal range.

PMID- 17016703
TI  - The effect of 18 h of simulated high altitude on left ventricular function.
AB  - High altitude produces increased pulmonary capillary pressure by hypoxia induced
      pulmonary vasoconstriction. It is also possible that hypoxia results in mildly
      elevated left ventricular (LV) filling pressures that may contribute to the
      elevated capillary pressures. This study investigates the impact of simulated
      high altitude on global and regional echocardiographic measures of LV performance
      and filling pressure. Seventeen healthy individuals underwent transthoracic
      echocardiography, including tissue Doppler of the septal mitral annulus and basal
      segments before and after an 18-h overnight stay in a high altitude simulation
      tent with a FiO(2) of 12%, simulating an altitude of approximately 4,000 m above
      sea level. In simulated high altitude, the ratio of early transmitral flow
      velocity to early myocardial relaxation velocity increased 22%, P < 0.001, and
      the Index of Myocardial Performance increased 30%, P < 0.01 due to an 58%
      increase in the isovolumic relaxation time (IVRT), P < 0.001. Simulated high
      altitude leads to a reduction in LV performance with an accompanying increase in
      markers of LV filling pressure. The significant changes in filling pattern and
      IVRT in the setting of normal and unchanged systolic function, indicates that
      hypoxia induces mild diastolic dysfunction in young healthy individuals.

PMID- 17016704
TI  - The effect of hetero- and homosexual experience and long-term treatment with
      fluoxetine on homosexual behavior in male rats.
AB  - INTRODUCTION: The selective serotonin reuptake inhibitors have become the most
      frequently prescribed drugs for the treatment of depression. Sexual side effects
      have been noted to occur with this treatment on heterosexual behavior in rats.
      Heterosexual experience facilitates sexual orientation of male rats and decreases
      the latencies to first mount and first intromission. On the other hand,
      homosexual behavior in male rats induced by female hormones has not been
      evaluated. AIM: The objective of this work is to evaluate the effects of
      heterosexual and homosexual experience in male rats long-term treated with
      fluoxetine (FLX) on homosexual hormone-induced behavior. MATERIALS AND METHODS:
      Male rats were treated with FLX or saline solution (10 mg/kg for 65 days). At
      days 36, 50, and 65 of the treatment, the rats were evaluated for homosexual
      behavior. Other rats treated with FLX or saline solution for 60 consecutive days
      were submitted to heterosexual behavior at 14, 21, and 28 days of the treatment.
      After this, they were orquiectomized and homosexual hormone-induced behavior was
      observed at 45 and 60 days of the treatment. RESULTS: (1) Only treatment with FLX
      did not affect the homosexual behavior. (2) The homosexual experience facilitated
      the homosexual behavior mainly on the animals from the control group. (3) The
      heterosexual experience facilitated the homosexual behavior on both groups.
      CONCLUSIONS: Only long-term administration of FLX does not interfere with the
      homosexual behavior in male rats. The homosexual and the heterosexual experience
      facilitated the homosexual behavior on the control and experimental groups. We
      suggested that learning aspects related to sexual behavior are responsible by
      these results.

PMID- 17016705
TI  - The nicotinic antagonist mecamylamine has antidepressant-like effects in wild
      type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout
      mice.
AB  - RATIONALE: Increases in cholinergic transmission are linked to depression in
      human subjects and animal models. We therefore examined the effect of decreasing
      nicotinic acetylcholine receptor (nAChR) activity in tests of antidepressant
      efficacy using C57BL/6J mice. OBJECTIVES: We determined whether the
      noncompetitive nAChR antagonist mecamylamine had antidepressant-like effects in
      the forced swim test (FST) and tail suspension test (TST). These experiments were
      repeated in mice lacking either the beta2- or alpha7-nAChR subunits to identify
      the nAChR subunits involved in mediating the antidepressant response to
      mecamylamine. MATERIALS AND METHODS: Adult mice on the C57BL/6J background were
      acutely administered mecamylamine i.p. 30 min before testing in the FST or TST.
      RESULTS: A dose-response study showed that mecamylamine significantly decreased
      immobility time in the TST at the 1.0-mg/kg dose but did not alter baseline
      locomotor activity. The competitive nAChR antagonist dihydro-beta-erythroidine,
      but not the blood-brain barrier impermeant antagonist hexamethonium, also
      decreased immobility in the TST. One milligram per kilogram of mecamylamine also
      significantly decreased time immobile in the FST whereas both beta2- and alpha7
      knockout mice were insensitive to the effects of mecamylamine in the FST.
      CONCLUSIONS: Decreased activity of central nAChRs has antidepressant-like effects
      in both the TST and FST and these effects are dependent on both beta2 and alpha7
      subunits. Therefore, compounds that decrease nAChR activity may be attractive new
      candidates for development as antidepressants in humans.

PMID- 17016706
TI  - Treatment with MDMA from P11-20 disrupts spatial learning and path integration
      learning in adolescent rats but only spatial learning in older rats.
AB  - RATIONALE: Previous studies in rats showed that postnatal day (P)11-20 exposure
      to +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes learning and
      memory deficits in adulthood. The emergence and permanence of these learning
      deficits are currently unknown. OBJECTIVE: This study was designed to investigate
      learning and memory deficits in adolescent (P30 or P40) and older (P180 or P360)
      rats exposed to MDMA from P11-20. MATERIALS AND METHODS: Within each litter half
      the animals were exposed to MDMA (20 mg/kg) and half to saline (SAL) twice a day
      (8 h apart) from P11-20. In experiment (exp) 1, behavioral testing began on
      either P30 or P40, whereas in exp 2, testing began on either P180 or P360.
      Offspring were tested in the Cincinnati water maze (CWM), a test of path
      integration learning (2 trials/day for 5 days), and the Morris water maze (MWM)
      (three phases, with 5 days of 4 trials/day and a probe trial on the sixth day per
      phase). RESULTS: MDMA-treated rats took longer to find the platform and traveled
      a greater distance to find the platform at all ages tested in all phases of the
      MWM. MDMA-treated animals also spent less time in the target quadrant during
      probe trials. In the CWM, P30 and P40 animals took longer to find the goal and
      committed more errors in locating the goal, while P180 and P360 MDMA-treated
      animals performed similarly to SAL-treated animals. CONCLUSION: The data suggest
      that the spatial learning and memory deficits induced by MDMA are long lasting,
      while the path integration deficits recover over time.

PMID- 17016707
TI  - Effects of stress modulation on morphine-induced conditioned place preferences
      and plasma corticosterone levels in Fischer, Lewis, and Sprague-Dawley rat
      strains.
AB  - RATIONALE: There is a direct relationship between hypothalamic-pituitary-adrenal
      axis (HPA) reactivity and susceptibility to drug use in outbred rats.
      Specifically, manipulations that increase or decrease HPA activity also increase
      or decrease drug intake, respectively. Interestingly, this relationship has not
      been established in the inbred Fischer (F344) and Lewis (LEW) rat strains that
      are often used as animal models of susceptibility to drug use. OBJECTIVE: The
      present study investigated the effects of manipulations known to affect HPA
      activity on morphine-induced conditioned place preference (CPP) in male LEW,
      F344, and Sprague-Dawley (SD) rats. MATERIALS AND METHODS: In experiment 1,
      animals were exposed to an injection of methyl-6,7-dimethoxy-4-ethyl-beta
      carboline-3-carboxylate (DMCM) and 2-h restraint stress prior to the conditioning
      of a morphine-induced place preference (1, 4, or 10 mg/kg subcutaneous). In
      experiment 2, animals were chronically exposed to corticotropin-releasing hormone
      type 1 receptor antagonist, antalarmin, prior to CPP training. The effects of
      DMCM/restraint and antalarmin on corticosterone levels were examined in
      experiments 3 and 4. RESULTS: In outbred rats, DMCM/restraint increased both HPA
      activity and morphine-induced CPP, while antalarmin decreased CPP and produced a
      slight, but nonsignificant, decrease in corticosterone levels. In the inbred
      rats, however, DMCM/restraint increased plasma corticosterone yet decreased place
      preferences in the LEW strain, and antalarmin treatment decreased plasma
      corticosterone but increased place preferences in the F344 strain. CONCLUSIONS:
      These data suggest that the relationship between stress and drug use may be
      nonmonotonic. The use of these inbred strains in genetic analysis of drug
      addiction may require reexamination.

PMID- 17016708
TI  - Relationship between limbic and cortical 5-HT neurotransmission and acquisition
      and reversal learning in a go/no-go task in rats.
AB  - RATIONALE: Specific brain structures have been suggested to be involved in
      impulsive responding assessed by a variety of operant tasks. Central serotonin (5
      HT) function has also been widely implicated in impulsivity; however, little
      research has addressed the regional aspect of 5-HT roles in different impulsive
      indices of task performance. OBJECTIVE: We analyzed the relationships between
      acquisition and reversal learning in a go/no-go task as different behavioral
      measures of impulsivity and focal concentrations of 5-HT and its metabolites in
      the brain. MATERIALS AND METHODS: Rats administered with parachloroamphetamine
      (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no
      go visual discrimination task. Neurochemical analysis was performed to determine
      5-HT concentrations in micropunched brain tissues. RESULTS: PCA administration
      induced regionally 5-HT depletion in the brain and impaired learning performance
      in both tests. For both tests, significant negative correlations between learning
      performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were
      observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast,
      significant negative correlations between learning performance and 5-HT and 5
      HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively
      in the reversal learning phase. CONCLUSIONS: The present data indicate that 5-HT
      neurotransmission to the mPFC and Amyg is involved in inhibitory control over
      responses to discriminated stimuli associated with the go/no-go paradigm common
      to both tests. In contrast, 5-HT neurotransmission to the OFC is especially
      involved in additional processes associated with reversal learning.

PMID- 17016709
TI  - Guanfacine produces differential effects in frontal cortex compared with
      striatum: assessed by phMRI BOLD contrast.
AB  - RATIONALE: Guanfacine (an alpha-(2A) adrenoreceptor agonist) is a drug of benefit
      in the treatment of attention deficit hyperactivity disorder (ADHD) (Taylor FB,
      Russo J, J Clin Psychopharmacol 21:223-228, 2001). Assessment of this drug using
      neuroimaging will provide information about the brain regions involved in its
      effects. OBJECTIVES: The pharmacological magnetic resonance imaging blood
      oxygenation level dependent (BOLD) response was determined in rat brain regions
      following administration of guanfacine. METHODS: Male rats were individually
      placed into a 2.35 T Bruker magnet for 60 min to achieve basal recording of
      changes in signal intensity. Either saline (n = 9) or guanfacine (0.3 mg/kg,
      i.p.; n = 9) was then administered and recording was continued for a further 90
      min. Data were analysed for BOLD effects using statistical parametric maps.
      Respiration rate, blood pressure and blood gases were monitored and remained
      constant throughout scanning. RESULTS: The main changes observed were negative
      BOLD effects in the caudate putamen and nucleus accumbens with positive BOLD
      effects in frontal association, prelimbic and motor cortex areas. CONCLUSIONS:
      These data suggest that guanfacine can decrease neuronal activity in the caudate
      while increasing frontal cortex activity. This ability to change neuronal
      activity in specific areas of rat brain that are known to be impaired in ADHD
      (Solanto MV, Behav Brain Res 130:65-71, 2002) may contribute to guanfacine's
      beneficial effects.

PMID- 17016710
TI  - Pain sensitivity is altered in animals after subchronic ketamine treatment.
AB  - RATIONALE: Clinical observations have shown that pain sensitivity is altered in
      some schizophrenic patients. OBJECTIVES: To study alterations in pain
      sensitivity, the ketamine model in schizophrenia research was employed. MATERIALS
      AND METHODS: Rats were subchronically injected with the dissociative anaesthetic
      ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of
      10 days). Two weeks after treatment completion, the animals' pain sensitivity was
      assayed in the hot plate test and they were subjected to electrical stimulation
      of the tail root. In addition, the effect of morphine was studied. RESULTS: In
      group-housed animals, there was no difference between Ket-injected animals and
      control rats as measured in both nociceptive tests. In singly housed Ket-injected
      rats, pain threshold was increased in the electrical stimulation test. This
      suggests that stress due to single housing might be essential for modifications
      of pain sensitivity. Moreover, the antinociceptive effect of morphine was
      modified after single housing. Interestingly, the effect of morphine on locomotor
      activity was similar in both groups. In group-housed rats, mu receptor binding
      was unchanged in the frontal cortex, whereas Ket-injected animals had decreased
      levels in the hippocampus. In singly housed animals, mu receptor binding in Ket
      injected rats increased in the frontal cortex and decreased in the hippocampus.
      (35)S-GTPgamma-S binding increased in the frontal cortex in both singly housed
      groups, but remained unchanged in the hippocampus. CONCLUSIONS: The data suggest
      that the ketamine model might be useful for studying altered pain sensitivity in
      schizophrenia. Moreover, the data suggest that modifications in mu opioid
      receptor binding contribute to this phenomenon.

PMID- 17016711
TI  - Different responses to dexamethasone and prednisolone in the same depressed
      patients.
AB  - RATIONALE: Patients with major depression show hypothalamic-pituitary-adrenal
      (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are
      still unclear. OBJECTIVES: We have compared two synthetic glucorticoids,
      dexamethasone and prednisolone, in their ability to suppress the hypothalamic
      pituitary-adrenal (HPA) axis in depressed patients. Dexamethasone probes
      glucocorticoid receptor (GR) function, while prednisolone probes both GR and
      mineralocorticoid receptor (MR) function. MATERIALS AND METHODS: We used a single
      blind, repeated-measure design. We administered placebo, prednisolone (5 mg) or
      dexamethasone (0.5 mg), at 22:00, to 18 severe, treatment-resistant depressed
      inpatients (15 of them with a history of childhood trauma) and 14 healthy
      volunteers. On the following days, we collected salivary cortisol from 9:00 to
      22:00. RESULTS: Depressed patients had higher salivary cortisol levels compared
      with controls, at baseline and after both prednisolone and dexamethasone
      (p<0.001). Consistent with previous studies, depressed inpatients showed impaired
      suppression by dexamethasone: based on the analysis of the areas under the curve
      (AUCs), suppression by dexamethasone (0.5 mg) was -85% in controls vs -46% in
      depressed patients (p=0.018). However, the same depressed patients showed normal
      suppression by prednisolone (5 mg): suppression was -41% in controls and -36% in
      depressed patients (p=0.6). CONCLUSIONS: We suggest that the additional effects
      of prednisolone on the MR explain the different responses to these
      glucocorticoids in the same depressed patients.

PMID- 17016712
TI  - Vulnerability of long-term neurotoxicity of chlorpyrifos: effect on schedule
      induced polydipsia and a delay discounting task.
AB  - INTRODUCTION: Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide
      that has been widely used in extensive agriculture as a pesticide. The primary
      mechanism of acute toxic action of OPs is inhibition of acetylcholinesterase
      (AChE). However, targets other than AChE have been proposed to contribute to the
      acute lethal action and side effects of short- or long-term exposure to these
      compounds. Bekkedal et al. (Sci Total Environ 274:119-123;2001) showed that
      chronic administration of the OP trimethylolpropane phosphate (TMPP) reduces the
      number of schedule-induced polydipsia (SIP) sessions necessary to induce
      asymptotic drinking level. MATERIALS AND METHODS: In the present work, rats were
      injected with 250 mg/kg CPF and 6 months later, its effect on schedule-induced
      polydipsia was evaluated. In addition, after stable levels of SIP, a
      pharmacological study was carried out to determine the implication of other
      systems in the long-term effects of OPs. Finally, these animals were evaluated in
      a delay discounting task, as a measure of impulsivity. RESULTS: Results indicate
      that the CPF group gives more licks to obtain the same amount of water than
      control rats (VHC). Moreover, the administration of diazepam produces an
      increased water intake in the CPF without any observable effect in VHC rats. Data
      of the delay discounting task show that CPF rats prefer an immediate reward and
      show a major impulsive choice. DISCUSSION: Taken together, our data confirm and
      extend the long-term behavioral effects of subcutaneous administration of CPF and
      point to a role for other systems that, besides AChE inhibition, contribute to
      the long-term neurotoxicity of CPF.

PMID- 17016713
TI  - Lorazepam dose-dependently decreases risk-taking related activation in limbic
      areas.
AB  - RATIONALE: Several studies have examined the role of different neurotransmitter
      systems in modulating risk-taking behavior. OBJECTIVE: This investigation was
      aimed to determine whether the benzodiazepine lorazepam dose-dependently alters
      risk-taking behavior and underlying neural substrates. MATERIALS AND METHODS:
      Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18-39 years
      (mean 27.6 +/- 1.4 years) with 12-18 years of education (mean 15.6 +/- 0.3 years)
      underwent functional magnetic resonance imaging while performing a risk-taking
      decision-making task. RESULTS: Our results show that lorazepam did not affect
      risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in
      (a) the amygdala and medial prefrontal cortex during the response selection
      phase, and in (b) the bilateral insular cortex and amygdala during the outcome
      (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in
      insular cortex activation was associated with less risky responses. CONCLUSIONS:
      Taken together, our findings support the idea that GABAergic modulation in limbic
      and paralimbic structures is important during both the response selection and
      outcome phase of risk-taking decision-making.

PMID- 17016714
TI  - A retrospective study of memantine in children and adolescents with pervasive
      developmental disorders.
AB  - RATIONALE: There are no drugs that have been shown to effectively treat the core
      social impairment of autism. OBJECTIVES: The purpose of this study was to examine
      the effectiveness and tolerability of memantine for social impairment in children
      and adolescents with pervasive developmental disorders (PDDs). MATERIALS AND
      METHODS: Medical records of 18 patients with PDDs consecutively treated with open
      label memantine were retrospectively reviewed. The data reviewed included
      prospectively obtained assessments of severity (S) and improvement (I) using the
      Clinical Global Impressions Scale (CGI). Pretrial and follow-up parent ratings
      were also available on six patients using the Aberrant Behavior Checklist (ABC).
      RESULTS: Eighteen patients (15 male, 3 female; mean age=11.4 years, range 6-19
      years) received memantine (mean dosage=10.1 mg/day, range 2.5-20 mg/day) over a
      mean duration of 19.3 weeks (range 1.5-56 weeks). Eleven of 18 (61%) patients
      were judged responders to memantine based on a rating of "much improved" or "very
      much improved" on the CGI-I. Significant improvement was also seen on the CGI-S.
      Improvement was primarily seen clinically in social withdrawal and inattention.
      Adverse effects occurred in 7 of 18 (39%) patients and led to drug
      discontinuation in 4 of 18 (22%) patients. Thirteen of 18 (72%) patients received
      stable doses of concomitant medications during the memantine trial. CONCLUSIONS:
      In this open-label retrospective study, memantine was effective in a number of
      patients with PDDs. Controlled studies are warranted to further assess the
      efficacy and safety of memantine in PDDs.

PMID- 17016715
TI  - Transcriptional changes in two types of pre-mycorrhizal roots and in
      ectomycorrhizas of oak microcuttings inoculated with Piloderma croceum.
AB  - The formation of the ectomycorrhiza implies an alteration in gene expression of
      both the plant and fungal partners, a process which starts before the formation
      of any symbiotic interface. However, little is known on the regulation pattern
      occurring in different parts of the root system. Our experimental system
      consisting of a micropropagated oak with a hierarchical root system was shown to
      exhibit symbiosis functional traits prior to any mycorrhizal tissue
      differentiation after the inoculation with the basidiomycete Piloderma croceum.
      Using a cDNA array, the plant gene regulation was analyzed in the pre-mycorrhizal
      phase. Seventy-five transcripts showed differential expression in pre-mycorrhizal
      lateral and principal roots, and both root types exhibited different sets of
      responsive genes. For transcripts selected according to a statistical analysis,
      the alteration in gene expression was confirmed by RT-PCR and quantitative real
      time PCR. Genes regulated in pre-mycorrhizal lateral roots displayed an almost
      identical expression in mycorrhizas. In contrast, genes regulated in pre
      mycorrhizal principal roots were often regulated differently in ectomycorrhizas.
      Down-regulation affected most of the regulated genes involved in metabolism,
      whereas most of the regulated genes related to cell rescue functions, water
      regulation and defence response were up-regulated. Regulation of such genes could
      explain the increase of global resistance observed in mycorrhizal plants.

PMID- 17016716
TI  - Passion for pathology: beauty is in the eye of the beholder.

PMID- 17016717
TI  - Prostatic tissue ectopia within the seminal vesicle: a potential source of
      confusion with seminal vesicle involvement by prostatic adenocarcinoma.

PMID- 17016718
TI  - Histopathologic indicators of recurrence in meningiomas: correlation with
      clinical and genetic parameters.
AB  - Meningiomas in general are circumscribed slow-growing tumors. However, despite
      gross total resection, tumor relapse and patients' outcome are still an issue.
      Risk stratification based on histomorphology alone remains problematic. This
      study explored the independent prognostic value of potential risk factors among
      206 patients who underwent meningioma resection and followed-up until death or a
      median of 44 months. The statistical analysis considered clinical data,
      histomorphologic parameters, cytogenetic findings, Ki-67 immunoreactivity, and
      activity of tissue non-specific alkaline phosphatase (ALPL). Recurrence-free
      survival estimates were computed and prognostic factors were identified using Cox
      proportional hazards model. Independent predictors of recurrence included (1)
      anaplasia; (2) mitotic index > or =20/10 high-power fields; (3) subtotal tumor
      resection; (4) loss of short arm of chromosome 1 (1p-); and (5) Ki-67 labeling
      index (LI) >12%. Among totally resected WHO grade I meningiomas, neither
      histopathologic nor clinical parameters were predictive, whereas 1p- was the only
      independent prognostic factor. ALPL did not reach significance in the
      multivariate modeling, however, the fast and low-cost histochemical detection of
      ALPL expression could be proved as a highly sensitive screening method for 1p-.
      In particular, biologically aggressive meningiomas of histologically benign or
      "borderline" phenotype could be therefore identified by ALPL detection followed
      by 1p in situ hybridization.

PMID- 17016719
TI  - Sclerosing pseudovascular rhabdomyosarcoma-immunohistochemical, ultrastructural,
      and genetic findings indicating a distinct subtype of rhabdomyosarcoma.
AB  - Sclerosing (pseudovascular) rhabdomyosarcoma in adults has been described as a
      rare variant of rhabdomyosarcoma characterized by extensive hyaline fibrosis and
      pseudovascular growth patterns. We describe another case of this rhabdomyosarcoma
      subtype including ultrastructural and genetic findings-the lesion presented in a
      62-year-old male patient in the left lower leg. The tumor was located within the
      deep soft tissue with maximum diameter of 11.8 cm and skin ulceration.
      Ultrastructural analysis revealed irregularly distributed disorganized filaments
      without clear evidence of Z-bands and a richly collagenized matrix. Using
      comparative genomic hybridization, a sharply delineated loss of chromosomal
      region 10q22, loss of chromosome Y, and a gain of chromosome 18 (trisomy) were
      detected. Reciprocal translocations t(1;13) and t(2;13)(q35;q14) which are
      characteristic of alveolar rhabdomyosarcoma could be excluded. These findings,
      while showing a relation to other rhabdomyosarcoma subtypes, represent a
      relatively circumscribed genetic defect pattern in sclerosing (pseudovascular)
      rhabdomyosarcoma that is somewhat different from patterns described in most other
      rhabdomyosarcoma subtypes. Six months after tumor resection, the patient
      presented with metastatic disease. Further studies should concentrate on the
      identification of genes especially on chromosomal region 10q22 to elucidate more
      aspects in the pathogenesis of this rhabdomyosarcoma subtype.

PMID- 17016720
TI  - Eccrine ductal and acrosyringeal differentiation of the breast epithelium--a
      lesion associated with some metaplastic breast carcinomas.
AB  - Two cases of metaplastic breast carcinoma associated with eccrine ductal
      metaplasia in the surrounding breast tissue are reported. The metaplastic
      epithelium deviated from the normal in its immunophenotype not expressing
      glandular cytokeratins (Cam 5.2) and estrogen receptors, being maspin-positive,
      and resembling morphologically different segments of dermal eccrine duct and
      acrosyringium. In addition, in one of the cases, basalioma-like intraductal cell
      proliferation was observed, also showing focal acrosyringeal differentiation. The
      invasive carcinomas, one of them representing "syringomatous squamous tumor of
      the breast" while the other diagnosed as high-grade metaplastic carcinoma, also
      showed focal eccrine and acrosyringeal differentiation and intensive diffuse
      maspin expression. These previously unrecognized metaplastic changes of the
      breast epithelium may represent precursor lesions of certain types of metaplastic
      breast carcinomas.

PMID- 17016721
TI  - Adamantinoma-like Ewing's sarcoma with EWS-FLI1 fusion gene: a case report.
AB  - Recent studies have advocated the genotypic and phenotypic delineation of a novel
      Ewing's sarcoma histologic variant showing epithelial features defined as
      "adamantinoma-like Ewing's sarcoma". We described an 18-year-old girl with a
      primary small round-cell sarcoma of the right tibia showing polyphenotypic
      differentiation with epithelioid features. The neoplastic cells had mainly round
      or oval nuclei with fine chromatin with a portion of epithelial arrangements. The
      immunohistochemical analysis showed the epithelial markers of cytokeratin 5/6/18,
      AE1/AE3, and cytokeratin high molecular weight were stained especially in the
      foci with epithelioid features, as well as MIC2, S100, and NSE. The diagnosis of
      the lesion was confirmed as Ewing's sarcoma by the presence of the EWS-FLI1
      fusion transcript, and could be defined as the so-called "adamantinoma-like
      Ewing's sarcoma". After wide excision and high-dose chemotherapy with peripheral
      blood stem cell transfusion, the patient has been well and continuously event
      free for 3 years since the initial diagnosis.

PMID- 17016722
TI  - Genetic variation in Opisthorchis viverrini (Trematoda: Opisthorchiidae) from
      northeast Thailand and Laos PDR based on random amplified polymorphic DNA
      analyses.
AB  - Genetic variation in Opisthorchis viverrini adults originating from different
      locations in northeast Thailand and Laos, People's Democratic Republic (PDR), was
      examined using random amplified polymorphic DNA (RAPD) analyses. In an initial
      analysis, the genomic DNA of one fluke from each of ten localities was amplified
      using 15 random primers (10-mers); however, genetic variation among O. viverrini
      specimens was detected reliably for only four primers. A more detailed RAPD
      analysis using these four primers was conducted on ten individuals from nine
      localities. Considerable genetic variation was detected among O. viverrini from
      different geographical areas and among some individuals from the same collecting
      locality. Comparison of the RAPD profiles revealed that O. viverrini adults from
      Laos PDR were genetically distinct from those from northeast Thailand. The
      taxonomic significance of this finding needs to be explored in more detail. The
      RAPD markers established in the present study provide opportunities to examine
      the biology and epidemiology of O. viverrini and fish-borne trematodes within the
      region. Additionally, application of these markers in such studies could have
      important implications in relation to the prevalence of cholangiocarcinoma in
      different regions of Asia.

PMID- 17016724
TI  - The giant liver fluke Fascioloides magna (Bassi 1875) in cervids in the Czech
      Republic and potential of its spreading to Germany.
AB  - The giant liver fluke Fascioloides magna is an important parasite of cervids in
      Europe. From September 2003 to December 2005, faecal samples and livers of red
      deer (Cervus elaphus) and fallow deer (Dama dama) were investigated to determine
      the current distribution of the fluke in the Czech Republic. Faecal samples were
      collected from 20 different areas, and livers of hunted deer were dissected from
      each locality to confirm F. magna infection. The prevalence of F. magna in
      examined areas determined by coprological examination varied from 4% to 95%.
      Moreover, new foci of F. magna infection were discovered in all localities in the
      Sumava mountains where F. magna was observed; this has epizootiological
      importance due to the possibility of the spread of F. magna into the German
      territory (Bavaria).

PMID- 17016723
TI  - Asymptomatic Enterocytozoon bieneusi microsporidiosis in captive mammals.
AB  - Human microsporidiosis, a serious disease of immunocompetent and immunosuppressed
      people, can be due to zoonotic transmission of microsporidian spores. A survey
      utilizing chromotrope 2R stain and fluorescent in situ hybridization techniques
      for testing feces from 193 captive mammals demonstrated that 3 animals (1.6%)
      shed Encephalitozoon bieneusi spores. These include two critically endangered
      species (i.e., black lemurs, Eulemur macaco flavifrons; and Visayan warty pig,
      Sus cebifrons negrinus) and a threatened species (mongoose lemur, Eulemur
      mongoz). The concentration of spores varied from 2.7 x 10(5) to 5.7 x 10(5)/g of
      feces, and all infections were asymptomatic. The study demonstrates that E.
      bieneusi spores can originate from captive animals, which is of particular
      epidemiologic importance because the close containment of zoological gardens can
      facilitate pathogen spread to other animals and also to people such as zoo
      personnel and visitors.

PMID- 17016725
TI  - Evaluation of an antigen-ELISA in the diagnosis of bovine cysticercosis in Kenyan
      cattle.
AB  - A monoclonal antibody-based antigen-ELISA (Ag-ELISA) was studied in Kenyan cattle
      with the objective of evaluating its reliability in diagnosing bovine
      cysticercosis. A total of 55 cattle divided into artificially (n = 30) and
      naturally (n = 25) infested animals, were utilized. Total dissection was used as
      a gold standard of validity at autopsy. In natural infestations, the assay
      identified 16 cases as true seropositives, 2 cases as false seropositives, 3
      cases as true seronegatives and 4 cases as false seronegatives. While in
      artificial infestations, the assay identified 9 cases as true seropositives, 14
      cases as true seronegatives and 7 cases as false seronegatives. There weren't any
      false seropositive cases identified with artificial infestations. The assay
      showed good precision level and kappa level in quantifying the relative quality
      of the amount of agreement in natural (n = 25; k = 0.482; p > 0.05) and
      artificial (n = 24; k = 0.374; p > 0.05) infestations. The study showed that,
      besides other advantages, the Ag-ELISA with its sensitivity of 60.00-80.00%,
      specificity of 60.00-100%, predictive value of 88.89-100%, apparent prevalence of
      37.50-72.00% and accuracy of 75.00-76.00% may be recommended for use in
      combination with other control measures, viz chemotherapy, post-mortem diagnosis
      and or vaccination.

PMID- 17016726
TI  - Evaluation of baculovirus-derived recombinant 53-kDa protein of Trichinella
      spiralis for detection of Trichinella-specific antibodies in domestic pigs by
      ELISA.
AB  - The complete gene encoding the 53-kDa protein derived from Trichinella spiralis
      was cloned and expressed using a baculovirus-based system. Characterization of a
      purified fusion protein consisting of the 53-kDa protein and the glutathione S
      transferase protein showed unspecific reactivity with swine pre-immune serum in
      both enzyme-linked immunosorbent assay (ELISA) and Western blot analysis.
      Subsequently, a purified C-terminal 6xHis-tagged 53-kDa protein was used in an
      ELISA. The evaluation of the test using a negative serum panel showed a high
      specificity for the ELISA. Serum panels of pigs infected with T. spiralis of two
      independent experiments showed that pigs of one experiment were tested positive
      by the ELISA, whereas all sera of the second experiment were negative, indicating
      a low sensitivity of the ELISA. Furthermore, experimental evidence was found by
      using mass spectroscopy and Western blot analysis that the 53-kDa protein was not
      part of the excretory/secretory antigen of T. spiralis as shown in this study.

PMID- 17016727
TI  - Taxonomic position and geographical distribution of the common sheep G1 and camel
      G6 strains of Echinococcus granulosus in three African countries.
AB  - The taxonomic and phylogenetic status of Echinococcus granulosus strains are
      still controversial and under discussion. In the present study, we investigated
      the genetic polymorphism of E. granulosus isolates originating from three
      countries of Africa, including a region of Algeria, where the common G1 sheep and
      the camel G6 strains coexist sympatrically. Seventy-one hydatid cysts were
      collected from sheep, cattle, camels, and humans. Two mitochondrial markers (cox1
      and nad1) were used for strain identification. Two nuclear markers (actII and
      hbx2) were used to study the possible occurrence of cross-fertilization. Despite
      the heterogeneity observed among the G1 isolates, they were all localized within
      one robust cluster. A second strong cluster was also observed containing all of
      the G6 isolates. Both strains appeared as two distinct groups, and no cases of
      interbreeding were found. Thus, the attribution of a species rank can be
      suggested. We also found the Tasmanian sheep G2 strain for the first time in
      Africa. Because of the slight variations observed between the common sheep and
      the Tasmanian sheep strains, further studies should be carried out to elucidate
      the epidemiological relevance of this genetic discrimination.

PMID- 17016728
TI  - Gene expression analysis of wild Leishmania major isolates: identification of
      genes preferentially expressed in amastigotes.
AB  - Trying to identify virulence genes of wild Leishmania (L.) major parasites, the
      species responsible for zoonotic cutaneous leishmaniasis, we compared, using
      differential display technique, gene expression in two L. major isolates obtained
      from human lesions and characterized by their contrasting pathogenicity in the
      BALB/c mouse model. The analysis was performed on amastigotes derived from BALB/c
      mice lesions. A total of 13 different clones were identified, but the use of
      reverse transcription and real-time polymerase chain reaction technique did not
      allow us to confirm any of these clones as differentially expressed. However, the
      fact that we used the amastigote stage of the parasite led us the identification
      of amastigote-specific genes, essentially (8 among 13). They are overexpressed,
      two to seven times, in amastigotes relative to promastigotes. Sequence analysis
      revealed that two of them namely LPG3 and the ATP dependent RNA helicase
      correspond to previously described amastigote-specific genes. The others
      correspond to genes involved in important biological process. Their better
      characterization could help the development of new drugs targeting the processes
      in which these molecules are involved.

PMID- 17016729
TI  - Immature triclabendazole-resistant Fasciola hepatica: tegumental responses to in
      vitro treatment with the sulphoxide metabolite of the experimental fasciolicide
      compound alpha.
AB  - Juvenile triclabendazole-resistant liver flukes, Fasciola hepatica, were
      incubated in vitro with 10 microg/ml of the sulphoxide metabolite of the
      experimental fasciolicide, compound alpha [5-chloro-2-methylthio-6-(1
      naphthyloxy)-1H-benzimidazole], for 6 and 18 h. Following treatment, the
      specimens were examined using scanning electron microscopy (SEM), transmission
      electron microscopy (TEM) and tubulin immunocytochemistry. The SEM results
      revealed a posterior-directed disruption comprised predominantly of swelling and
      blebbing of the tegument; these changes were more severe and extensive after the
      longer 18-h incubation. Along with swelling of the tegument and blebbing, the TEM
      results also revealed swelling of the mitochondria and basal infolds. A decrease
      in the number of both T1 and T2 secretory bodies was observed in the syncytium
      and cytoplasmic connections after the 18-h treatment. The circular muscle bundles
      were also disrupted, in that the organisation of the muscle fibres was irregular
      and the total number of muscle fibres was reduced. The immunocytochemical studies
      revealed no significant disruption to the distribution of tubulin
      immunoreactivity within the tegumental syncytium, the cytoplasmic connections or
      the associated tegumental cells. The results indicate that alpha.SO is capable of
      disrupting the tegument of 4-week-old triclabendazole-resistant liver flukes,
      though the morphological changes were not associated with any significant
      differences in tubulin immunostaining.

PMID- 17016730
TI  - Artificial consciousness, artificial emotions, and autonomous robots.
AB  - Nowadays for robots, the notion of behavior is reduced to a simple factual
      concept at the level of the movements. On another hand, consciousness is a very
      cultural concept, founding the main property of human beings, according to
      themselves. We propose to develop a computable transposition of the consciousness
      concepts into artificial brains, able to express emotions and consciousness
      facts. The production of such artificial brains allows the intentional and really
      adaptive behavior for the autonomous robots. Such a system managing the robot's
      behavior will be made of two parts: the first one computes and generates, in a
      constructivist manner, a representation for the robot moving in its environment,
      and using symbols and concepts. The other part achieves the representation of the
      previous one using morphologies in a dynamic geometrical way. The robot's body
      will be seen for itself as the morphologic apprehension of its material
      substrata. The model goes strictly by the notion of massive multi-agent's
      organizations with a morphologic control.

PMID- 17016731
TI  - Evolution of teleostean hatching enzyme genes and their paralogous genes.
AB  - We isolated genes for hatching enzymes and their paralogs having two cysteine
      residues at their N-terminal regions in addition to four cysteines conserved in
      all the astacin family proteases. Genes for such six-cysteine-containing astacin
      proteases (C6AST) were searched out in the medaka genome database. Five genes for
      MC6AST1 to 5 were found in addition to embryo-specific hatching enzyme genes. RT
      PCR and whole-mount in situ hybridization evidenced that MC6AST1 was expressed in
      embryos and epidermis of almost all adult tissues examined, while MC6AST2 and 3
      were in mesenterium, intestine, and testis. MC6AST4 and 5 were specifically
      expressed in jaw. In addition, we cloned C6AST cDNA homologs from zebrafish, ayu,
      and fugu. The MC6AST1 to 5 genes were classified into three groups in the
      phylogenetic positions, and the expression patterns and hatching enzymes were
      clearly discriminated from other C6ASTs. Analysis of the exon-intron structures
      clarified that genes for hatching enzymes MHCE and MAHCE were intron-less, while
      other MC6AST genes were basically the same as the gene for another hatching
      enzyme MLCE. In the basal Teleost, the C6AST genes having the ancestral exon
      intron structure (nine exon/eight intron structure) first appeared by duplication
      and chromosomal translocation. Thereafter, maintaining such ancestral exon-intron
      structure, the LCE gene was newly diversified in Euteleostei, and the MC6AST1 to
      5 gene orthologs were duplicated and diversified independently in respective fish
      lineages. The HCE gene lost all introns in Euteleostei, whereas in the lineage to
      zebrafish, it was translocated from chromosome to chromosome and lost some of its
      introns.

PMID- 17016732
TI  - The human and mouse H19 imprinting control regions harbor an evolutionarily
      conserved silencer element that functions on transgenes in Drosophila.
AB  - Differentially methylated regions have been characterized at a number of
      imprinted gene complexes with important roles in the regulation of monoallelic
      expression of one or more genes. The differentially methylated imprinting control
      region (ICR) located upstream of the murine H19 gene has been shown to control
      the imprinted expression of H19 and the coordinately regulated Igf2 gene by
      acting as a transcriptional silencer. In this study, we show that the murine ICR
      maintains this function when tested in an in vivo transgenic Drosophila assay in
      the absence of DNA methylation. Furthermore, the H19 ICR interacts distinctively
      with Drosophila promoters of different regulatory strengths. We also demonstrate
      that the comparable region upstream of the human H19 gene is a multipartite cis
      regulatory element, demonstrating silencing function when tested in mammalian and
      Drosophila systems. These results indicate a conservation of the H19/Igf2
      imprinting mechanism between humans and mice and further elucidate the functional
      activities of the H19 ICR. They demonstrate the value of Drosophila as an in vivo
      system for testing function and interaction of eukaryotic regulatory elements and
      that mechanisms of transcriptional cis-regulation in mammals and Drosophila are
      conserved.

PMID- 17016733
TI  - Transgenic Indian mustard (Brassica juncea) expressing tomato glucanase leads to
      arrested growth of Alternaria brassicae.
AB  - Brassica juncea is an important oilseed crop of the Indian sub-continent. Yield
      loss due to fungal disease alternaria leaf spot caused by Alternaria brassicae is
      a serious problem in cultivation of this crop. Nonavailability of resistance
      genes within crossable germplasms of Brassica necessitates use of genetic
      engineering strategies to develop genetic resistance against this pathogen. The
      pathogenesis related (PR) proteins are group of plant proteins that are toxic to
      invading fungal pathogens, but are present in plant in trace amount. Thus,
      overexpression of PR proteins leads to increased resistance to pathogenic fungi
      in several crops. The PR protein glucanase hydrolyzes a major cell-wall
      component, glucan, of pathogenic fungi and acts as a plant defense barrier. We
      report the expression of a class I basic glucanase gene, under the control of
      CaMV 35S promoter, in Indian mustard and its genetic resistance against
      alternaria leaf spot. Southern and Northern hybridization confirmed stable
      integration and expression of the glucanase gene in mustard transgenics. Several
      independent transgenics were screened in vitro and under poly house conditions
      for their resistance against Alternaria brassicae. In an in vitro antifungal
      assay, transgenics arrested hyphal growth of Alternaria brassicae by 15-54%.
      Under pathogen-challenged conditions in poly house, the transgenics showed
      restricted number, size and spread of lesions caused by Alternaria brassicae.
      Also, the onset of disease was delayed in transgenics compared to untransformed
      parent plants. The results demonstrate potentiality of a PR protein from a
      heterologous source in developing alternaria leaf spot resistance in Indian
      mustard.

PMID- 17016734
TI  - An efficient, in vitro cyclic production of shoots from adult trees of Crataeva
      nurvala Buch. Ham.
AB  - An efficient, cyclic, two-step protocol for micropropagation of medicinal tree,
      Crataeva nurvala has been successfully developed, which can be employed at a
      commercial scale. Nodal explants from 30-year-old tree when cultured on MS medium
      supplemented with 2.22 microM BAP produced multiple shoots, which elongated
      satisfactorily on the same medium. Nodal and leaf explants from in vitro
      regenerated microshoots too developed shoots, thus making the process recurrent.
      In 6-month duration, owing to the recurring nature of the protocol, over 5400
      shoots could be produced from a single nodal explant from the adult tree.
      Addition of casein hydrolysate significantly increased the average number of
      shoots per explant. Maximum number of shoots regenerated on medium supplemented
      with 100 mg l(-1) casein hydrolysate. Shoots could be rooted on 1/2 MS
      supplemented with 0.11 and 0.54 microM NAA. Regenerated plantlets were
      acclimatized and successfully transplanted to soil.

PMID- 17016735
TI  - The PsEND1 promoter: a novel tool to produce genetically engineered male-sterile
      plants by early anther ablation.
AB  - PsEND1 is a pea anther-specific gene that displays very early expression in the
      anther primordium cells. Later on, PsEND1 expression becomes restricted to the
      epidermis, connective, endothecium and middle layer, but it is never observed in
      tapetal cells or microsporocytes. We fused the PsEND1 promoter region to the
      cytotoxic barnase gene to induce specific ablation of the cell layers where the
      PsEND1 is expressed and consequently to produce male-sterile plants. Expression
      of the chimaeric PsEND1::barnase gene in two Solanaceae (Nicotiana tabacum and
      Solanum lycopersicon) and two Brassicaceae (Arabidopsis thaliana and Brassica
      napus) species, impairs anther development from very early stages and produces
      complete male-sterile plants. The PsEND1::barnase gene is quite different to
      other chimaeric genes previously used in similar approaches to obtain male
      sterile plants. The novelty resides in the use of the PsEND1 promoter, instead of
      a tapetum-specific promoter, to produce the ablation of specific cell lines
      during the first steps of the anther development. This chimaeric construct
      arrests the microsporogenesis before differentiation of the microspore mother
      cells and no viable pollen grains are produced. This strategy represents an
      excellent alternative to generate genetically engineered male-sterile plants,
      which have proved useful in breeding programmes for the production of hybrid
      seeds. The PsEND1 promoter also has high potential to prevent undesirable
      horizontal gene flow in many plant species.

PMID- 17016736
TI  - Phototoxic effects of commercial photographic flash lamp on rat eyes.
AB  - BACKGROUND: To determine whether exposure of the cornea and retina of rats to
      flashes from a commercial photographic flash lamp is phototoxic. METHODS: Sprague
      Dawley rats were exposed to 10, 100, or 1,000 flashes of the OPTICAM 16M
      photographic flash lamp (Fujikoeki, Japan) placed 0.1, 1, or 3 m from the eyes.
      Corneal damage was assessed by a fluorescein staining score, and the retinal
      damage by eletroretinography (ERG) and histology before and 24 h after exposure.
      RESULTS: Exposure of the eyes to 1,000 flashes at 0.1 m increased the fluorescein
      staining score significantly (P = 0.009, the Mann-Whitney test). Scanning
      electron microscopy (SEM) of the cornea showed a detachment of the epithelial
      cells from the surface after this exposure. The amplitude of the a-wave was
      decreased significantly by 23.0% (P = 0.026) of the amplitude before the
      exposure, and the b-wave by 19.7% (P = 0.0478) following 1,000 flashes at 0.1 m
      but not by the other exposures. TUNEL-positive cells were present in the outer
      nuclear layer only after the extreme exposure, but no significant decrease in
      retinal thickness was seen under any condition. The fluorescein staining score
      and ERGs recovered to control levels within 1 week. CONCLUSIONS: Light exposure
      to a photographic flash lamp does not induce damage to the cornea and retina
      except when they are exposed to 1,000 flashes at 0.1 m.

PMID- 17016737
TI  - A comparison between exocytic control mechanisms in adrenal chromaffin cells and
      a glutamatergic synapse.
AB  - It has been known since the work of Katz and collaborators in the early 1950s
      that an increase in intracellular Ca(++) concentration ([Ca(++)]) is the
      immediate trigger for neurotransmitter release. Later work has shown that, next
      to Ca(++), many other signaling pathways, particularly via cyclic AMP, modulate
      the release of both neurotransmitters and hormones. However, regulated secretion
      is a multistep process and the signaling mechanisms involved act at many stages.
      Biochemical and traditional electrophysiological techniques very often cannot
      distinguish whether a change in secretion is caused by regulation of ion
      channels, vesicle trafficking, or the exocytic process itself. My laboratory has
      made an effort to dissect the stimulus secretion pathway by developing assays in
      chromaffin cells (for catecholamine release) and at a glutamatergic central
      nervous synapse (the calyx of Held, a component of the auditory pathway), which
      permit the study of secretion in single cells under voltage clamp conditions.
      This enables us to clearly distinguish between consequences of changes in
      electrical signaling, from those regarding the process of vesicle recruitment or
      the process of exocytosis.

PMID- 17016738
TI  - Differential integration of kinaesthetic signals to postural control.
AB  - The purpose of the present experiment was to identify whether non-visual sensory
      cues involved in the maintenance of balance control could be weighted differently
      from one subject to another in condition during which kinaesthetic signals,
      stemming from the ankle proprioceptors and plantar pressure somatosensory
      sensors, were altered. A large population of blindfolded healthy young university
      students (n = 140) were asked to sway as little as possible on: (1) a firm
      support (Firm condition) and (2) an unstable support used to impair the
      exploitation of the kinematic ankle proprioceptive and plantar pressure
      somatosensation (Foam condition). Centre of foot pressure (CoP) displacements
      were recorded using a force platform. Analyses of the surface area, range, and
      mean velocity of the CoP displacements showed significant negative correlations
      between the postural sway observed in the Firm condition and the increase in
      postural sway observed in the Foam condition. In other words, the alteration of
      ankle proprioception had a greater destabilising effect in subjects exhibiting
      the smallest CoP displacements when standing in a normal proprioception
      condition. The present findings suggest that the exploitation of the kinaesthetic
      relationships to postural control varied from one subject to another, hence
      evidencing the need to introduce differential approach to assess the general
      impact of preferential modes of spatial referencing in postural control.

PMID- 17016740
TI  - Transcriptional and metabolic profiles of stress-induced, embryogenic tobacco
      microspores.
AB  - Higher plant microspores, when subjected to various stress treatments in vitro,
      are able to reprogram their regular gametophytic development towards the
      sporophytic pathway to form haploid embryos and plants. Suppression subtractive
      hybridization (SSH) and metabolic profiling were used to characterize this
      developmental switch. Following differential reverse Northern hybridizations 90
      distinct up-regulated sequences were identified in stressed, embryogenic
      microspores (accessible at www.univie.ac.at/ntsm). Sequence analyses allowed the
      classification of these genes into functional clusters such as metabolism,
      chromosome remodeling, signaling, transcription and translation, while the
      putative functions of half of the sequences remained unknown. A comparison of
      metabolic profiles of non-stressed and stressed microspores using gas
      chromatography/mass spectrometry (GC/MS) identified 70 compounds, partly
      displaying significant changes in metabolite levels, e.g., highly elevated levels
      of isocitrate and isomaltose in stressed microspores compared to non-stressed
      microspores. The formation of embryogenic microspores is discussed on the basis
      of the identified transcriptional and metabolic profiles.

PMID- 17016741
TI  - Comparison of maize brown-midrib isogenic lines by cellular UV
      microspectrophotometry and comparative transcript profiling.
AB  - The molecular mechanisms underlying cell wall digestibility in maize (Zea mays
      L.) have been studied in three sets of maize brown-midrib isogenic lines in the
      genetic background of inbreds 1332 (1332 and 1332 bm3), 5361 (5361 and 5361 bm3),
      and F2 (F2, F2 bm1, F2 bm2, and F2 bm3). Two complementary approaches, SSH
      (suppression subtractive hybridization) and microarray-based expression
      profiling, were used to isolate and identify candidate genes in isogenic lines
      for bm mutants. Metabolic pathway analysis revealed that transcriptional events
      caused by altering the expression of a single bm gene involve all metabolic and
      signaling pathways. 53 ESTs were differentially expressed in all three isogenic
      bm3 comparisons, whereas 32 ESTs were consistently differentially expressed in
      different bm isogenic lines in F2 background. About 70% ESTs isolated by SSH were
      not present on the unigene microarray, demonstrating the usefulness of the SSH
      procedure to identify genes related to cell wall digestibility. Together with
      lignin analysis by cellular UV-microspectrophotometry, expression profiling in
      isogenic bm lines proved to be useful to understand alterations at the sub
      cellular and molecular level with respect to lignin composition. The down
      regulation of COMT affected the expression of CCoAOMT genes and caused a reduced
      content both of G and S units in bm3 mutants.

PMID- 17016742
TI  - Polyhydroxyalkanoates in Gram-positive bacteria: insights from the genera
      Bacillus and Streptomyces.
AB  - Gram-positive bacteria, notably Bacillus and Streptomyces, have been used
      extensively in industry. However, these microorganisms have not yet been
      exploited for the production of the biodegradable polymers, polyhydroxyalkanoates
      (PHAs). Although PHAs have many potential applications, the cost of production
      means that medical applications are currently the main area of use. Gram-negative
      bacteria, currently the only commercial source of PHAs, have lipopolysaccharides
      (LPS) which co-purify with the PHAs and cause immunogenic reactions. On the other
      hand, Gram- positive bacteria lack LPS, a positive feature which justifies
      intensive investigation into their production of PHAs. This review summarizes
      currently available knowledge on PHA production by Gram- positive bacteria
      especially Bacillus and Streptomyces. We hope that this will form the basis of
      further research into developing either or both as a source of PHAs for medical
      applications.

PMID- 17016743
TI  - APHO1 from the yeast Arxula adeninivorans encodes an acid phosphatase of broad
      substrate specificity.
AB  - The extracellular acid phosphatase-encoding Arxula adeninivorans APHO1 gene was
      isolated using degenerated specific oligonucleotide primers in a PCR screening
      approach. The gene harbours an ORF of 1449 bp encoding a protein of 483 amino
      acids with a calculated molecular mass of 52.4 kDa. The sequence includes an N
      terminal secretion sequence of 17 amino acids. The deduced amino acid sequence
      exhibits 54% identity to phytases from Aspergillus awamori, Asp. niger and Asp.
      ficuum and a more distant relationship to phytases of the yeasts Candida albicans
      and Debaryomyces hansenii (36-39% identity). The sequence contains the
      phosphohistidine signature and the conserved active site sequence of acid
      phosphatases. APHO1 expression is induced under conditions of phosphate
      limitation. Enzyme isolates from wild and recombinant strains with the APHO1 gene
      expressed under control of the strong A. adeninivorans-derived TEF1 promoter were
      characterized. For both proteins, a molecular mass of approx. 350 kDa,
      corresponding to a hexameric structure, a pH optimum of pH 4.8 and a temperature
      optimum of 60 degrees C were determined. The preferred substrates include p
      nitrophenyl-phosphate, pyridoxal-5-phosphate, 3-indoxyl-phosphate, 1
      naphthylphosphate, ADP, glucose-6-phosphate, sodium-pyrophosphate, and phytic
      acid. Thus the enzyme is a secretory acid phosphatase with phytase activity and
      not a phytase as suggested by strong homology to such enzymes.

PMID- 17016744
TI  - Comparison of intracranial pressure measured simultaneously within the brain
      parenchyma and cerebral ventricles.
AB  - We report a 48-year-old man treated for acute subarachnoid hemorrhage (SAH)
      wherein intracranial pressure (ICP) was measured simultaneously within the
      ventricular cerebrospinal fluid (CSF) and the brain parenchyma (PAR). Single
      pressure waves within the continuous pressure signal were identified with
      determination of the single wave parameters pulse amplitude (i.e. pressure
      difference between diastolic minimum pressure and systolic maximum pressure),
      mean pressure (i.e. mean pressure from beginning to ending minimum diastolic
      minimum pressure), and latency (i.e. rise time from diastolic minimum pressure to
      systolic maximum pressure). A total of 218,589 CSF/PAR single pressure wave pairs
      were analyzed. For these CSF/PAR wave pairs the mean difference in pulse pressure
      amplitude was -0.13 mmHg [95% confidence interval (CI) -0.13 to -0.12 mmHg], mean
      difference in mean single wave pressure -0.71 mmHg (95% CI -0.74 to -0.68 mmHg),
      and mean difference in latency -0.01 seconds (95% CI -0.01 to -0.01 seconds).
      Hence, in this patient monitoring ICP within the ventricular CSF or brain
      parenchyma gave similar results. Moreover, the comparisons of single CSF/PAR wave
      pulse pressure amplitudes gave no evidence of a pressure gradient from brain
      parenchyma to the ventricular CSF in this patient.

PMID- 17016745
TI  - Mechanism of enhanced conversion of 1,2,3-trichloropropane by mutant haloalkane
      dehalogenase revealed by molecular modeling.
AB  - 1,2,3-Trichloropropane (TCP) is a highly toxic, recalcitrant byproduct of
      epichlorohydrin manufacture. Haloalkane dehalogenase (DhaA) from Rhodococcus sp.
      hydrolyses the carbon-halogen bond in various halogenated compounds including
      TCP, but with low efficiency (k (cat)/K (m )= 36 s(-1) M(-1)). A Cys176Tyr-DhaA
      mutant with a threefold higher catalytic efficiency for TCP dehalogenation has
      been previously obtained by error-prone PCR. We have used molecular simulations
      and quantum mechanical calculations to elucidate the molecular mechanisms
      involved in the improved catalysis of the mutant, and enantioselectivity of DhaA
      toward TCP. The Cys176Tyr mutation modifies the protein access and export routes.
      Substitution of the Cys residue by the bulkier Tyr narrows the upper tunnel,
      making the second tunnel "slot" the preferred route. TCP can adopt two major
      orientations in the DhaA enzyme, in one of which the halide-stabilizing residue
      Asn41 forms a hydrogen bond with the terminal halogen atom of the TCP molecule,
      while in the other it bonds with the central halogen atom. The differences in
      these binding patterns explain the preferential formation of the (R)- over the
      (S)-enantiomer of 2,3-dichloropropane-1-ol in the reaction catalyzed by the
      enzyme.

PMID- 17016746
TI  - A marriage made in torsional space: using GALAHAD models to drive pharmacophore
      multiplet searches.
AB  - Pharmacophore multiplets are useful tools for 3D database searching, with the
      queries used ordinarily being derived from ensembles of random conformations of
      active ligands. It seems reasonable to expect that their usefulness can be
      augmented by instead using queries derived from single ligand conformations
      obtained from aligned ligands. Comparisons of pharmacophore multiplet searching
      using random conformations with multiplet searching using single conformations
      derived from GALAHAD (a genetic algorithm with linear assignment for
      hypermolecular alignment of datasets) models do indeed show that, while query
      hypotheses based on random conformations are quite effective, hypotheses based on
      aligned conformations do a better job of discriminating between active and
      inactive compounds. In particular, the hypothesis created from a neuraminidase
      inhibitor model was more similar to half of 18 known actives than all but 0.2% of
      the compounds in a structurally diverse subset of the World Drug Index.
      Similarly, a model developed from five angiotensin II antagonists yielded
      hypotheses that placed 65 known antagonists within the top 0.1-1% of decoy
      databases. The differences in discriminating power ranged from 2 to 20-fold,
      depending on the protein target and the type of pharmacophore multiplet used.

PMID- 17016747
TI  - Defining the nucleotide binding sites of P2Y receptors using rhodopsin-based
      homology modeling.
AB  - Ongoing efforts to model P2Y receptors for extracellular nucleotides, i.e.,
      endogenous ADP, ATP, UDP, UTP, and UDP-glucose, were summarized and correlated
      for the eight known subtypes. The rhodopsin-based homology modeling of the P2Y
      receptors is supported by a growing body of site-directed mutagenesis data,
      mainly for P2Y(1) receptors. By comparing molecular models of the P2Y receptors,
      it was concluded that nucleotide binding could occur in the upper part of the
      helical bundle, with the ribose moiety accommodated between transmembrane domain
      (TM) 3 and TM7. The nucleobase was oriented towards TM1, TM2, and TM7, in the
      direction of the extracellular side of the receptor. The phosphate chain was
      oriented towards TM6, in the direction of the extracellular loops (ELs), and was
      coordinated by three critical cationic residues. In particular, in the P2Y(1),
      P2Y(2), P2Y(4), and P2Y(6) receptors the nucleotide ligands had very similar
      positions. ADP in the P2Y(12) receptor was located deeper inside the receptor in
      comparison to other subtypes, and the uridine moiety of UDP-glucose in the
      P2Y(14) receptor was located even deeper and shifted toward TM7. In general,
      these findings are in agreement with the proposed binding site of small molecules
      to other class A GPCRs.

PMID- 17016748
TI  - Invasive species and coal bed methane development in the Powder River Basin,
      Wyoming.
AB  - One of the fastest growing areas of natural gas production is coal bed methane
      (CBM) due to the large monetary returns and increased demand for energy from
      consumers. The Powder River Basin, Wyoming is one of the most rapidly expanding
      areas of CBM development with projections of the establishment of up to 50,000
      wells. CBM disturbances may make the native ecosystem more susceptible to
      invasion by non-native species, but there are few studies that have been
      conducted on the environmental impacts of this type of resource extraction. To
      evaluate the potential effects of CBM development on native plant species
      distribution and patterns of non-native plant invasion, 36 modified Forest
      Inventory and Analysis plots (each comprised of four 168-m2 subplots) were
      established in the Powder River Basin, Wyoming. There were 73 168-m2 subplots on
      control sites; 42 subplots on secondary disturbances; 14 on major surface
      disturbances; eight on well pads; and seven on sites downslope of CBM wells water
      discharge points. Native plant species cover ranged from 39.5 +/- 2.7% (mean +/-
      1 SE) in the secondary disturbance subplots to 17.7 +/- 7.5% in the pad subplots.
      Non-native plant species cover ranged from 31.0 +/- 8.4% in the discharge areas
      to 14.7 +/- 8.9% in the pad subplots. The control subplots had significantly less
      non-native species richness than the combined disturbance types. The combined
      disturbance subplots had significantly greater soil salinity than the control
      sites. These results suggest that CBM development and associated disturbances may
      facilitate the establishment of non-native plants. Future research and management
      decisions should consider the accumulative landscape-scale effects of CBM
      development on preserving native plant diversity.

PMID- 17016749
TI  - A long term study of the desiccation resistance of Drosophila melanogaster and D.
      simulans from the Mexican nuclear power plant "Laguna Verde".
AB  - The generation of electricity through the use of radioactive material at the
      nuclear power plant is inevitably associated with the production of wastes, some
      of which have potential impact on the biosphere. The objective of the present
      investigation was to provide information for evaluating the presumed impact of
      the Mexican Nuclear Power Plant "Laguna Verde" on the natural populations. Two
      sibling species that live in the immediate vicinity, Drosophila melanogaster and
      D. simulans have been studied for several traits in a long term study. The
      present study describes results for the desiccation resistance (DR) trait
      obtained during the period from 1995 to 2002. Flies were collected at two sites,
      one near the reactors and another farther away. The data obtained confirmed that
      D. melanogaster had higher DR values than D. simulans at both sites. The analysis
      of the results obtained from both species of the site closer to the reactor
      indicated that the values of the DR in the operational stage did not change,
      compared with those in the preoperational stage previously analyzed. Therefore,
      the significant differences found between the monitored sites did not seem to be
      associated to the operation of the reactors.

PMID- 17016750
TI  - Polycyclic aromatic hydrocarbons in bulk PM2.5 and size-segregated aerosol
      particle samples measured in an urban environment.
AB  - To analyze polycyclic aromatic hydrocarbons (PAHs) at an urban site in Seoul,
      South Korea, 24-hr ambient air PM2.5 samples were collected during five intensive
      sampling periods between November 1998 and December 1999. To determine the PAH
      size distribution, 3-day size-segregated aerosol samples were also collected in
      December 1999. Concentrations of the 16 PAHs in the PM2.5 particles ranged from
      3.9 to 119.9 ng m(-3) with a mean of 24.3 ng m(-3). An exceptionally high
      concentration of PAHs( approximately 120 ng m(-3)) observed during a haze event
      in December 1999 was likely influenced more by diesel vehicle exhaust than by
      gasoline exhaust, as well as air stagnation, as evidenced by the low carbon
      monoxide/elemental carbon (CO/EC) ratio of 205 found in this study and results
      reported by previous studies. The total PAHs associated with the size-segregated
      particles showed unimodal distributions. Compared to the unimodal size
      distributions of PAHs with modal peaks at < 0.12 microm measured in highway
      tunnels in Los Angeles (Venkataraman and Friedlander, 1994), four- to six-ring
      PAHs in our study had unimodal size distributions, peaking at the larger size
      range of 0.28-0.53 microm, suggesting the coagulation of freshly emitted
      ultrafine particles during transport to the sampling site. Further, the fraction
      of PAHs associated with coarse particles(> 1.8 microm) increased as the molecular
      weight of the PAHs decreased due to volatilization of fine particles followed by
      condensation onto coarse particles.

PMID- 17016751
TI  - Application of artificial neural network approach and remotely sensed imagery for
      regional eco-environmental quality evaluation.
AB  - Eco-environment quality evaluation is an important research theme in environment
      management. In the present study, Fuzhou city in China was selected as a study
      area and a limited number of 222 sampling field sites were first investigated in
      situ with the help of a GPS device. Every sampling site was assessed by
      ecological experts and given an Eco-environment Background Value (EBV) based on a
      scoring and ranking system. The higher the EBV, the better the ecological
      environmental quality. Then, three types of eco-environmental attributes that are
      physically-based and easily-quantifiable at a grid level were extracted: (1)
      remote sensing derived attributes (vegetation index, wetness index, soil
      brightness index, surface land temperature index), (2) meteorological attributes
      (annual temperature and annual precipitation), and (3) terrain attribute
      (elevation). A Back Propagation (BP) Artificial Neural Network (ANN) model was
      proposed for the EBV validation and prediction. A three-layer BP ANN model was
      designed to automatically learn the internal relationship using a training set of
      known EBV and eco-environmental attributes, followed by the application of the
      model for predicting EBV values across the whole study area. It was found that
      the performance of the BP ANN model was satisfactory and capable of an overall
      prediction accuracy of 82.4%, with a Kappa coefficient of 0.801 in the
      validation. The evaluation results showed that the eco-environmental quality of
      Fuzhou city is considered as satisfactory. Through analyzing the spatial
      correlation between the eco-environmental quality and land uses, it was found
      that the best eco-environmental areas were related to forest lands, whereas the
      urban area had the relatively worst eco-environmental quality. Human activities
      are still considered as a major impact on the eco-environmental quality in this
      area.

PMID- 17016752
TI  - Organochlorine pesticide residues in ground water of Thiruvallur district, India.
AB  - Modern agriculture practices reveal an increase in use of pesticides and
      fertilizers to meet the food demand of increasing population which results in
      contamination of the environment. In India crop production increased to 100% but
      the cropping area has increased marginally by 20%. Pesticides have played a major
      role in achieving the maximum crop production, but maximum usage and accumulation
      of pesticide residues was highly detrimental to aquatic and other ecosystem. The
      present study was chosen to know the level of organochlorines contamination in
      ground water of Thiruvallur district, Tamil Nadu, India. The samples were highly
      contaminated with DDT, HCH, endosulfan and their derivatives. Among the HCH
      derivatives, Gamma HCH residues was found maximum of 9.8 microg/l in Arumbakkam
      open wells. Concentrations of pp-DDT and op-DDT were 14.3 microg/l and 0.8
      microg/l. The maximum residue (15.9 microg/l) of endosulfan sulfate was recorded
      in Kandigai village bore well. The study showed that the ground water samples
      were highly contaminated with organochlorine residues.

PMID- 17016753
TI  - Monitoring of heavy metal partitioning in reef corals of Lakshadweep Archipelago,
      Indian Ocean.
AB  - This paper focuses on the partitioning of trace metals in five selected coral
      species from Lakshadweep Archipelago, which remains as one of the least studied
      areas in the Indian Ocean. Based on the morphological features, selected coral
      species are classified as massive (Porites andrewsi), ramose or branching
      (Lobophyllia corymbosa, Acropora formosa and Psammocora contigua) and foliaceous
      (Montipora digitata). Relating trace metal concentrations with morphological
      features in skeleton, highest concentrations of all the trace metals (except Zn)
      were reported for the ramose type corals. In tissue, all the metals (essential as
      well as non essential) showed highest concentrations within the branching type
      corals. Irrespective of their growth characteristics/pattern, all species except
      P. contigua displayed higher concentrations of Pb, Ni, Mn and Cd within their
      skeleton compared to tissue which may exemplify a regulatory mechanism to avoid
      the build up of the concentrations of these metals in their bio-part, strikingly
      toxic metals like Cd and Pb. The concentrations of trace metals in the skeleton
      and tissues of these coral species were subjected to 3 way ANOVA based on non
      standardized original data and the results showed significant differences between
      metals and between species leading to high skeleton/ tissue - species interaction
      as well as skeleton/tissue - metal interaction. The significant values of
      student's t calculated are depicted in the form of Trellis diagrams.

PMID- 17016754
TI  - Evaluation of ogawa passive sampling devices as an alternative measurement method
      for the nitrogen dioxide annual standard in El Paso, Texas.
AB  - Nitrogen Dioxide (NO(2)) is a common urban air pollutant that results from the
      combustion of fossil fuels. It causes serious human health effects, is a
      precursor to the formation of ground level ozone, another serious air pollutant,
      and is one of the six criteria air pollutants established by the United States
      (U.S.) Clean Air Act (CAA). Ogawa Passive Sampling Devices (PSDs) for NO(2) were
      collocated and operated at six NO(2) Federal Reference Method (FRM) monitor
      locations in the El Paso, Texas area for the 2004 calendar year. Passive samples
      were taken at 2-week, 3-week, and 4-week intervals and compared against the
      continuously operating FRM monitors. Results showed that the collective NO(2)
      annual arithmetic mean for all passive monitors was identical to the NO(2) mean
      for all FRM monitors. Of the individual locations, three passive annual NO(2)
      means were identical to their corresponding FRM means, and three passive annual
      NO(2) means differed from their corresponding FRM means by only one part per
      billion (ppb). Linear correlation analysis between all readings of the individual
      NO(2) PSDs and FRM values showed an average absolute difference of 1.2 ppb with
      an r (2) of 0.95. Paired comparison between high and low concentration annual
      NO(2) sites, seasonal considerations, and interlab quality control comparisons
      all showed excellent results. The ease of deployment, reliability, and the cost
      savings that can be realized with NO(2) PSDs could make them an attractive
      alternative to FRM monitors for screening purposes, and even possibly an
      equivalent method for annual NO(2) monitoring. More tests of the Ogawa NO(2) PSD
      are recommended for different ecosystem and climate regimes.

PMID- 17016755
TI  - Survival analysis and clinicopathological factors associated with false-negative
      sentinel lymph node biopsy findings in patients with cutaneous melanoma.
AB  - BACKGROUND: We analyzed the outcomes and factors associated with false-negative
      (FN) results of sentinel lymph node (SLN) biopsy findings in patients with
      cutaneous melanoma. SLN biopsy failure rate was defined as nodal recurrence in
      the biopsied regional basin without previous local or in-transit recurrence.
      METHODS: Between April 1997 and December 2004, a total of 1207 patients with
      cutaneous melanoma with a median Breslow thickness of 2.4 mm underwent SLN biopsy
      by preoperative and intraoperative lymphoscintigraphy combined with dye
      injection. In 228 cases, we found positive SLNs; of these, 220 underwent
      completion lymph node dissection (CLND). Median follow-up was 3 years. RESULTS:
      The SLN biopsy failure rate was 5.8% (57 of 979 SLN negative). Median time to
      occurrence of FN relapse after SLN biopsy was 16 months (range, 3-74 months). The
      FN SLN biopsy results correlated with primary tumor thickness >4 mm (P = .0012),
      primary tumor ulceration (P = .0002), primary tumor level of invasion Clark stage
      IV/V (P = .0005), and nodular melanoma histological type (P = .0375). Five-year
      overall survival, calculated from the date of primary tumor excision, in the FN
      group was 53.7%, which was not statistically significantly worse than the CLND
      group (56.8%; P = .9). The FN group was characterized by a higher ratio of two or
      more metastatic nodes and extracapsular involvement of lymph nodes after LND
      compared with the CLND group (P < .0001 and P < .0001, respectively). Additional
      detailed pathological review of FN SLN revealed metastatic disease in 14
      patients, which decreased the SLN biopsy failure rate to 4.4% (43 of 979).
      CONCLUSIONS: Survival of patients with FN results of SLN biopsy does not differ
      statistically significantly from that of patients undergoing CLND, although it is
      slightly lower. The SLN biopsy failure rate is approximately 5.0% in long-term
      follow-up and is associated mainly with the same factors that indicate a poor
      prognosis in primary melanoma.

PMID- 17016756
TI  - References and reading lists for imaging informatics professionals: preparing for
      certification.

PMID- 17016757
TI  - Imipramine-induced facial pigmentation: case report and literature review.
AB  - BACKGROUND: Patients who present with facial pigmentation can be a diagnostic
      challenge. OBJECTIVE: The goal of this study was to discuss the diagnosis and
      management of imipramine-induced facial pigmentation. METHODS: We describe a
      patient with facial pigmentation of 26 years' duration that was associated with
      imipramine treatment for depression. We discuss light and election microscopic
      findings and review 11 previously reported cases of imipramine-induced skin
      pigmentation. RESULTS: Examination showed blue-gray facial pigmentation. Light
      microscopy showed perivascular pigment granule deposits in the upper dermis that
      stained positively with Fontana-Masson stain and negatively with Prussian blue
      stain. Electron microscopy showed electron-dense bodies within histiocytes
      without clearly identifiable melanin granules, consistent with drug-induced
      pigmentation. Six weeks after switching to sertraline the patient reported a
      slight improvement of her cutaneous pigmentation. CONCLUSION: Imipramine is a
      rare cause of gray-blue facial pigmentation. Light microscopy consistently shows
      granular dermal deposits that stain positively with Fontana-Masson stain but
      negatively with iron stain.

PMID- 17016758
TI  - Perceptions of a community sample about participation in future HIV vaccine
      trials in south India.
AB  - Focus group discussions were conducted to assess factors that might impact
      participation of subgroups in Chennai for future HIV vaccine trials. The
      participants were 112 men and women representing the following: (1) transport
      workers; (2) clients who attended a sexually transmitted disease clinic; (3)
      injection drug users; (4) men having sex with men; (5) women in sex work; and (6)
      monogamous married women. Participants expressed an intense interest in future
      HIV vaccine trials. Willingness to participate in future trials included altruism
      and the desire to have a protective vaccine for the future. Assurances regarding
      stigma and confidentiality, and compensation for families in the event of a poor
      outcome with a future HIV vaccine trial were reported. Concerns also centered on
      the impact of seroconverting, and a possible increase in risk behaviors. The need
      for education and counseling about the dangers of engaging in risky behavior
      during and after participating in a future HIV vaccine trial is discussed.

PMID- 17016759
TI  - Repeat voluntary HIV counseling and testing (VCT), sexual risk behavior and HIV
      incidence in Rakai, Uganda.
AB  - We examined the effects of repeat Voluntary HIV counseling and testing (VCT) on
      sexual risk behaviors and HIV incidence in 6,377 initially HIV-negative subjects
      enrolled in a prospective STD control for HIV prevention trial in rural Rakai
      district, southwestern Uganda. Sixty-four percent accepted VCT, and of these,
      62.2% were first time acceptors while 37.8% were repeat acceptors. Consistent
      condom use was 5.8% in repeat acceptors, 6.1% in first time acceptors and 5.1% in
      non-acceptors. A higher proportion of repeat acceptors (15.9%) reported
      inconsistent condom use compared to first-time acceptors (12%) and non-acceptors
      (11.7%). Also, a higher proportion of repeat acceptors (18.1%) reported 2+ sexual
      partners compared to first-time acceptors (14.1%) and non-acceptors (15%). HIV
      incidence rates were 1.4/100 py (person-years) in repeat acceptors, 1.6/100 py in
      first time acceptors and 1.6/100 py in non-acceptors. These data suggest a need
      for intensive risk-reduction counseling interventions targeting HIV-negative
      repeat VCT acceptors as a special risk group.

PMID- 17016760
TI  - Development and psychometric evaluation of a self-administered questionnaire to
      measure knowledge of sexually transmitted diseases.
AB  - This research developed and evaluated a brief but comprehensive measure of
      knowledge about sexually transmitted diseases (STDs) for use in research and
      applied settings. Questionnaire construction involved a review of empirical
      precedents as well as qualitative work with STD experts (n = 6) and the target
      population (n = 40). Eighty-five items were piloted (n = 50) and tested (n = 391)
      with college students. Item- and test-level analyses identified items that were
      eliminated to shorten the questionnaire. Factor analyses revealed a two-factor
      model of STD knowledge, including a Cause/Cure factor and a General Knowledge
      factor. Six supplemental items were added to the final questionnaire for their
      public health value and resulted in the 27-item STD-Knowledge Questionnaire (STD
      KQ). The STD-KQ demonstrated internal consistency (alpha = .86) and test-retest
      reliability (r = .88) over a brief period. Evidence for the validity of the STD
      KQ was obtained through a comparison with a validated HIV knowledge questionnaire
      (Carey & Schroder, 2002); treatment outcome sensitivity was obtained in response
      to an educational program. Use of the STD-KQ will enable researchers and health
      educators to identify knowledge deficits, measure knowledge for theory testing,
      evaluate risk reduction programs, and assess treatment response in research and
      applied settings.

PMID- 17016761
TI  - Planar biaxial creep and stress relaxation of the mitral valve anterior leaflet.
AB  - A fundamental assumption in mitral valve (MV) therapies is that a repaired or
      replaced valve should mimic the functionality of the native valve as closely as
      possible. Thus, improvements in valvular treatments are dependent on the
      establishment of a complete understanding of the function and mechanical
      properties of the native normal MV. In a recent study [Grashow et al. ABME 34(2),
      2006] we demonstrated that the planar biaxial stress-strain relationship of the
      MV anterior leaflet (MVAL) exhibited minimal hysteresis and a stress-strain
      response independent of strain rate, suggesting that MVAL could be modeled as a
      "quasi-elastic" material. The objective of our current study was to expand these
      results to provide a more complete picture of the time-dependent mechanical
      properties of the MVAL. To accomplish this, biaxial stress-relaxation and creep
      studies were performed on porcine MVAL specimens. Our primary finding was that
      while the MVAL leaflet exhibited significant stress relaxation, it exhibited
      negligible creep over the 3-h test. These results furthered our assertion that
      the MVAL functionally behaves not as a linear or non-linear viscoelastic
      material, but as an anisotropic quasi-elastic material. These results appear to
      be unique in the soft tissue literature; suggesting that valvular tissues are
      unequalled in their ability to withstand significant loading without time
      dependent material effects. Moreover, insight into these specialized
      characteristics can help guide and inform efforts directed toward surgical repair
      and engineered valvular tissue replacements.

PMID- 17016762
TI  - Microstructural characteristics of extracellular matrix produced by stromal
      fibroblasts.
AB  - The overall objective of this investigation was to characterize the extracellular
      matrix deposited by the stromal fibroblasts as a function of time in culture and
      matrix microstructure. Stromal fibroblasts were seeded onto collagen matrices and
      cultured for up to 5 weeks. The collagen matrices contained collagen fibrils with
      an average diameter of 215 +/- 20 nm. When cultured on a collagen film, an
      average fibril diameter of 62 +/- 39 nm was observed for single layer films with
      only slight variations with time in culture, and after 1 week of culture between
      two film layers 67 +/- 47 nm fibrils were observed after 1 week. When the film
      surface was molded into 1 and 2 microm microgrooves, the initial average fibril
      diameter of the extracellular matrix was 73 +/- 21 and 73 +/- 31 nm respectively.
      When cultured on a collagen sponge, an average fibril diameter of 107 +/- 20 nm
      was initially observed and decreased to 47.5 +/- 17 nm after 1 week in culture.
      For cells cultured on a collagen sponge, Western blotting showed an increase in
      myofibroblast phenotype expression with time in culture. Shifts in phenotype were
      less distinct for cells cultured on collagen films. The microstructure, rather
      than geometry, of the matrix substrate appeared to influence the newly
      synthesized extracellular matrix and cell phenotype.

PMID- 17016763
TI  - The multifaceted roles of chemokines in malignancy.
AB  - Tumor development and progression are multifactorial processes, regulated by a
      large variety of intrinsic and microenvironmental factors. A key role in cancer
      is played by members of the chemokine superfamily. Chemokines and their receptors
      are expressed by tumor cells and by host cells, in primary tumors and in specific
      metastatic loci. The effects of chemokines on tumorigenesis are diverse: While
      some members of the superfamily significantly support this process, others
      inhibit fundamental events required for tumor establishment and metastasis. The
      current review describes the multifaceted roles of chemokines in malignancy,
      addressing four major aspects of their activities: (1) inducing leukocyte
      infiltration to tumors and regulating immune functions, with emphasis on tumor
      associated macrophages (and the chemokines CCL2, CCL5), T cells (and the
      chemokines CXCL9, CXCL10) and dendritic cells (and the chemokines CCL19, CCL20,
      CCL21); (2) directing the homing of tumor cells to specific metastatic sites (the
      CXCL12-CXCR4 axis); (3) regulating angiogenic processes (mainly the ELR(+)-CXC
      and non-ELR-CXC chemokines); (4) acting directly on the tumor cells to control
      their malignancy-related functions. Together, these different chemokine functions
      establish a net of interactions between the tumor cells and their
      microenvironment, and partly dictate the fate of the malignancy cascade.

PMID- 17016764
TI  - Medicare payment changes and nursing home quality: effects on long-stay
      residents.
AB  - The Balanced Budget Act of 1997 dramatically changed the way that Medicare pays
      skilled nursing facilities, providing a natural experiment in nursing home
      behavior. Medicare payment policy (directed at short-stay residents) may have
      affected outcomes for long-stay, chronic-care residents if services for these
      residents were subsidized through cost-shifting prior to implementation of
      Medicare prospective payment for nursing homes. We link changes in both the form
      and level of Medicare payment at the facility level with changes in resident
      level quality, as represented by pressure sores and urinary tract infections in
      Minimum Data Set (MDS) assessments. Results show that long-stay residents
      experienced increased adverse outcomes with the elimination of Medicare cost
      reimbursement.

PMID- 17016765
TI  - Thermal biofeedback for primary Raynaud's phenomenon: a review of the literature.
AB  - The clinical presentation of primary Raynaud's phenomenon (RP) derives from
      various pathogenic triggers. The use of thermal biofeedback (TBF) may be of
      benefit in reducing the severity and frequency of attacks. This article
      summarizes the relevant research regarding the pathophysiology of primary RP and
      mechanism of TBF for RP. Systematic reviews of the efficacy of TBF for RP and
      treatment guidelines for clinicians are provided. The panel concludes that the
      level of evidence for TBF efficacy is categorized as Level IV: efficacious. The
      rationale, based on three randomized controlled trials conducted in independent
      laboratories, demonstrated "superiority or equivalence" of treatments that
      include TBF. However, randomly controlled trials (RCT) with positive clinical
      outcomes tended to be small. A large RCT with negative results did not
      effectively teach handwarming skills. Procedures for reviewing and rating of the
      levels of evidence of efficacy of studies was based on the Template for
      Developing Guidelines for the Evaluation of the Clinical Efficacy of
      Psychophysiological Interventions developed by the joint task force of the AAPB
      and the Society for Neuronal Regulation (SNR).

PMID- 17016767
TI  - European neuroscience - Federation of European Neuroscience Societies 5th Forum.
      8-12 July 2006, Vienna, Austria.

PMID- 17016766
TI  - Do socioeconomic effects on health diminish with age? A Singapore case study.
AB  - This paper examines the effects of socioeconomic characteristics on older adult
      health and investigates whether these socioeconomic effects carry through from
      the young-old to the oldest-old ages among Singaporean adults. Previous research
      shows little consensus over whether the impact of socioeconomic factors on health
      diminish with age. The variation in these results may be due to different
      definitions of socio-economic status, or the use of different health indicators.
      We use a comprehensive set of socioeconomic indicators (income, education level,
      homeownership, asset possession, and perceived income adequacy) to predict three
      health outcomes; poor self-assessed health, the presence of chronic illness, and
      functional disability. We find that while socioeconomic differentials in health
      status exist, the associations are not as consistent, nor as strong, as those
      reported for Western settings. Health inequalities related with socioeconomic
      status decline slightly but do not disappear with old age in Singapore.

PMID- 17016768
TI  - Biodiversity and natural products - IUPAC International Conference (ICOB-5 and
      ISCNP-25).

PMID- 17016769
TI  - Prostate cancer - 6th International Congress.

PMID- 17016770
TI  - Animal, plant and microbial toxins - 15th World Congress.

PMID- 17016771
TI  - Obesity drug development - CBI's 2nd Annual Summit.

PMID- 17016772
TI  - AIDS 2006 - XVI International Conference. Time to deliver.

PMID- 17016773
TI  - Industrial microbiology and biotechnology - 2006 Annual Meeting.

PMID- 17016774
TI  - International Narcotics Research Conference (INRC) 2006.

PMID- 17016775
TI  - Novel vaccines: bridging research, development and production - CHI's Inaugural
      Conference.

PMID- 17016776
TI  - Back to the science of stem cell research - CHI's 2nd Annual Meeting.

PMID- 17016777
TI  - Pluripotent human stem cells as novel tools in drug discovery and toxicity
      testing.
AB  - Improved technologies are urgently needed to develop effective and safe new drugs
      in a cost-efficient manner. Cell-based assays have many advantages in drug
      research, particularly because these assays can be adapted in a high-throughput
      format. In addition, technological advances in the areas of instrumentation and
      automation are providing expanding opportunities for high-content analyses.
      However, in cell-based research, none of these systems is particularly useful
      unless the cells that are being evaluated are clinically relevant. Pluripotent
      human stem cells are expected to revolutionize the accessibility to a variety of
      human cell types. The possibility to propagate pluripotent human stem cells and
      to subsequently differentiate these cells into desired target cell types will
      provide a stable supply of cells for a range of applications in drug discovery
      and toxicity testing. This feature discusses some of the research opportunities
      for pluripotent human stem cells.

PMID- 17016778
TI  - The application of locked nucleic acids in the treatment of cancer.
AB  - Locked nucleic acid (LNA) is a novel high-affinity and biologically stable RNA
      analog in which the normally flexible ribose sugar ring is fixed in a rigid
      conformation through a methylene 2'-O, 4'-C linkage. This fixed conformation
      brings substantial advantages to the design of effective RNA binding drugs, and
      enables single-stranded LNA oligonucleotides, termed 'RNA antagonists', to have
      superior efficacies in vivo in downregulating target mRNA when compared to
      oligonucleotides based on other chemistries or to published short interfering
      RNA. The features that allow LNA to be a valuable drug platform include
      unprecedented RNA binding affinity, excellent specificity, resistance to
      enzymatic degradation, safety, and ease of manufacture. Santaris Pharma A/S holds
      worldwide rights to the application of LNA in therapeutics, and is engaged in the
      clinical development of a series of drug candidates against cancer and metabolic
      diseases. SPC-2996, the company's most advanced product in development, entered
      an international, open-label, multicenter, phase I/II clinical trial in patients
      with severe chronic lymphocytic leukemia in May 2005. This trial is the first
      clinical evaluation of LNA chemistry. Two other LNA compounds have completed good
      laboratory practice safety studies with satisfactory outcome, and are likely to
      commence undergoing clinical development by 2007.

PMID- 17016779
TI  - Drug evaluation: forodesine - PNP inhibitor for the treatment of leukemia,
      lymphoma and solid tumor.
AB  - Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage
      metabolic pathway. In humans, the loss of functional PNP results in significant T
      cell-mediated immunodeficiency (and may also affect B-cell function). Forodesine
      is a potent PNP inhibitor that acts by elevating plasma 2'-deoxyguanosine (dGuo)
      and intracellular deoxyguanosine triphosphate, which in turn affects
      deoxynucleotide-triphosphate pools and induces cell death by apoptosis. BioCryst
      Pharmaceuticals Inc, under license from the Albert Einstein College of Medicine,
      is developing intravenous and oral formulations of forodesine for the potential
      treatment of various T-cell and B-cell lymphomas and leukemias, as well as for
      solid tumors; MundiPharma AG is also investigating the drug for leukemia.
      Forodesine effectively inhibits T-cell proliferation in vitro in the presence of
      dGuo. In early clinical trials, forodesine has demonstrated an acceptable safety
      profile and indications of biological activity. Few drug-related serious adverse
      events have been reported, and generally only mild-to-moderate nonhematological
      toxicity has been observed. Forodesine has the potential to lead the development
      of other novel therapies with broad-based activity for hematological
      malignancies; the drug may also be useful for the treatment of a wide variety of
      other T-cell-mediated disorders, as well as for the potential treatment for other
      B-cell lymphomas/leukemias.

PMID- 17016780
TI  - New paradigms in infectious eye disease: adenoviral keratoconjunctivitis.

PMID- 17016781
TI  - [Low use of laboratory tests in the diagnosis of the ocular surface].

PMID- 17016782
TI  - [Systematic review of population-based studies of the prevalence of cataracts].
AB  - OBJECTIVE: The prevalence of cataracts has increased due to the progressive
      ageing of the population and the fact that cataracts affect a wide and increasing
      proportion of the population. The goal of the present study was to describe the
      prevalence of cataracts through a systematic and exhaustive review of population
      based studies. METHODS: A systematic review of population-based studies of the
      prevalence and incidence of cataracts was performed. Inclusion criteria were: a
      healthy non- institutionalised population, older than 40 years of age, of white
      race, with a sample size of greater than 1,000 and published between 1980 and
      2002. RESULTS: Ten studies met the inclusion criteria (3 European, 5 from the
      United States and 2 from Australia), and were performed between 1984 and 2001.
      The cataract prevalence, according to lens opacity criteria, ranged between 15%
      and 19%. When the cataract was defined as a lens opacity combined with a
      decreased visual acuity, the prevalence ranged from 15% to 30%. The overall
      prevalence increased with age, reaching 40% and more than 60% in populations
      older than 70 and 75 years respectively. The prevalence among women was higher
      than that among men, with a more marked increase being evident at older ages than
      for men. CONCLUSIONS: There were variations among the criteria used to measure
      the prevalence of cataract, which made it difficult to compare all the studies.
      Overall the prevalence was higher in the older population, especially among
      women. The increasing prevalence associated with age predicts an increasing
      burden of cataract to health services, this being particularly related to the
      ageing of the population.

PMID- 17016783
TI  - [Needle revision of late failing filtering blebs after glaucoma surgery].
AB  - PURPOSE: To evaluate the results of bleb needling in eyes subjected to filtering
      surgery six months or more previously. METHODS: A retrospective study of 23 eyes
      in 21 patients subjected to bleb needling performed by means of a 25G needle, 6
      months to 23 years after failed filtering surgery (mean 67.3 months). The mean
      number of bleb needlings was 1.2 and the mean number of 5-fluorouracil
      subconjunctival injections was 3.9. RESULTS: The mean intraocular pressure (IOP)
      before needling was 26 mmHg and the mean anti-glaucoma medications was 1.3 per
      eye. The mean postoperative IOP was 16.3 mmHg and mean anti-glaucoma medications
      0.7. A diffuse filtering bleb was evident in 12 eyes (54.5%). The results of
      needling were worse in eyes subjected to previous surgery for glaucoma or other
      failed bleb needling procedures (75% failure). CONCLUSION: Needle revision of the
      filtering bleb is a simple and safe technique that offers good results even years
      after a filtering surgery had been performed. It should be considered before
      other medical or surgical treatments in patients with a previously functioning
      bleb and a permeable sclerectomy site at gonioscopy.

PMID- 17016784
TI  - [Variation of central corneal thickness in diabetic patients as detected by
      ultrasonic pachymetry].
AB  - OBJECTIVE: To prove the existence of a correlation between central corneal
      thickness and diabetes. METHODS: Ultrasound pachymetry measurements were made in
      1,000 patients. The sample was divided into two groups of patients: 953 of them
      were non-diabetic patients, and 47 were diabetic patients. RESULTS: The average
      central corneal thickness in diabetic patients was 571.96 +/- 26.81 microns with
      a range between 514 and 626. The average central corneal thickness found in non
      diabetic patients was 544.89 +/- 35.36 microns with range of 448 to 649. The
      increase in central corneal thickness found in diabetic patients compared to non
      diabetic patients was statistically significant (p<0.001, Student "t" test).
      CONCLUSIONS: We found that diabetic patients had an increased central corneal
      thickness when compared with non-diabetic patients.

PMID- 17016785
TI  - [Trabeculoplasty with two different lasers in cats, monkeys and humans: a
      scanning electron microscopy study].
AB  - PURPOSE: To study the structural changes induced by trabeculoplasty with two
      different lasers (Ti-Sph and argon) and observe the differences between four
      trabecular meshwork models. MATERIALS AND METHODS: Four different trabecular
      meshwork (TM) models were used from cats, monkeys, and humans. This study was
      performed on fresh cadaver eyes ("ex vivo") except for the cat in which this
      study was performed "in vivo". The morphology of the trabecular meshwork was
      observed by scanning electron microscope (40/100X) after being treated with argon
      (0.1s/pulse, 600 to 1,000 mW, 50 microm spot size) and Ti-Sph (7 microsg/pulse,
      25 to 110 mJ,175 microm of spot size). The study on cats allowed assessment of
      the induced effect after 24 hours, and 4 weeks after the treatment on the TM.
      Typical clinical trabeculoplasty parameters were used for both lasers during this
      study. RESULTS: The models used in this study were found to be adequate for
      trabeculoplasty. They exhibited a deep anterior chamber and an accessible TM. The
      argon laser induced significant changes in the TM in all models studied. The cat
      model demonstrated TM repair response one month after treatment. For Ti-Sph, high
      levels of energy (>100 mJ) were required to induce significant structural changes
      in the TM. CONCLUSION: The IOP reduction effect by argon trabeculoplasty
      (600/1,000 mW) induced structural shrinkage of the collagen in the TM via thermal
      effects. The Ti-Sph laser works through non-structural mechanisms. At clinical
      levels (lower than 80 mJ), Ti-Sph does not show evidence of TM changes.

PMID- 17016786
TI  - [Diagnostic ability of stratus optical coherence tomography (OCT) in pre
      perimetric glaucoma diagnosis].
AB  - OBJECTIVE: To compare retinal nerve fiber layer (RNFL) measurements performed
      with Stratus OCT 3000 in normal, ocular hypertensive, pre-perimetric and
      glaucomatous eyes. METHODS: 98 normal subjects, 156 ocular hypertensives with
      short-wavelength automated perimetry (SWAP), 21 ocular hypertensives with altered
      SWAP (pre-perimetric glaucoma) and 66 glaucomatous eyes were included in the
      study. Diagnostic groups were classified based on intraocular pressure, optic
      nerve head appearance, achromatic automatic perimetry and SWAP. RNFL parameters
      were obtained using a Stratus OCT 3000 (Humphrey Zeiss instruments). RNFL
      measurements were compared among the groups. RESULTS: RNFL average thickness,
      superior, inferior and nasal quadrant thickness, and each 12 clock-hour positions
      except for H9, H10 and H11 showed significant differences between glaucomatous
      and pre-perimetric glaucoma eyes. RNFL average thickness, inferior quadrant and
      H10 clock-hour position showed significant differences between normal and ocular
      hypertensive subjects. Pre-perimetric glaucomas and ocular hypertensives showed
      differences in H11 clock-hour position exclusively. CONCLUSION: RNFL measurements
      performed using Stratus OCT showed differences between the study groups. OCT may
      be as useful as SWAP in early glaucoma diagnosis.

PMID- 17016787
TI  - [Diffuse uveal melanoma. A clinical case].
AB  - CASE REPORT: We report the case of a 58-year-old man who presented at our
      emergency department with ocular pain and progressive loss of vision in his left
      eye. Ophthalmic examination detected a pigmented mass in the iridocorneal angle,
      involving the ciliary body. Glaucoma had also developed secondary to the
      melanotic lesion. Ophthalmoscopy showed a large pigmented choroidal tumor. After
      enucleation, pathologic examination confirmed the diagnosis of a diffuse ocular
      melanoma. DISCUSSION: Diffuse uveal melanoma is a malignant tumor that
      metastasises early. Enucleation is the treatment of choice.

PMID- 17016788
TI  - [Retinal neovascularization in a traumatic microhyphema].
AB  - CLINICAL CASE: This is a case of retinal ischaemia with subsequent
      neovascularization, in a 13 year-old boy who sustained a traumatic hyphema after
      blunt trauma. DISCUSSION: Hyphemas can occur after blunt trauma, intraocular
      surgery, spontaneously and in association with the use of substances that alter
      platelet or thrombin function (aspirin, ethanol). Associated injuries are
      traumatic anterior uveitis, iridodialysis, optic atrophy, secondary hemorrhage
      and a traumatic cataract. This case illustrates the formation of retinal
      neovascularization in association with a microhyphema and the need for careful
      and prolonged ophthalmological examination in this clinical context.

PMID- 17016789
TI  - [Optical coherence tomography in central retinal artery occlusion].
AB  - CLINICAL CASES: Three eyes with central retinal artery occlusion (CRAO) have been
      studied. Optical coherence tomography (OCT) was performed in each of them.
      Ophthalmoscopic signs of CRAO were equivocal in the three eyes. However, the
      presence of a hyporeflective signal in the OCT scan could be seen clearly in each
      of them. DISCUSSION: The presence of a hyporeflective band between the
      neurosensory retina and the retinal pigment epithelium in OCT images, that
      persist for several months after a CRAO episode, is useful in establishing the
      diagnosis in these patients.

PMID- 17016790
TI  - [The pioneer use of nitrogen mustard by Emilio Roda Perez in the treatment of
      idiopathic uveitis].

PMID- 17016791
TI  - [1914--deception of Theodor Axenfeld].

PMID- 17016792
TI  - Development, implementation and prospective evaluation of guidelines for transfer
      of severely injured children to specialist centres.
AB  - BACKGROUND: Most injured children are appropriately treated at a district general
      hospital (DGH), but some require transfer to a specialist centre. The objectives
      of this study were to develop, implement and evaluate triage guidelines for the
      rapid recognition of injured children who require transfer. METHODS: This was a
      prospective, interventional cohort study of the 592 seriously injured children
      who presented to five regional DGHs during a 51-month period. A multispecialty
      steering group representing all participating DGHs developed and implemented the
      guidelines. Data were collected for 24 months before the guidelines were
      introduced, over the 3-month implementation period and for 24 months afterwards.
      Outcome measures were referral and management patterns before and after
      introduction of the guidelines. RESULTS: For level I (unstable) patients, after
      the implementation of guidelines there was a 29 per cent increase in the
      proportion of transfers to a specialist centre (from 40 (68 per cent) of 59 to 32
      (97 per cent) of 33; P = 0.003), no admissions to a DGH intensive care unit and
      all 12 operations were performed at a specialist centre. Guideline users
      indicated that they were familiar with the guidelines. CONCLUSION: The
      introduction of triage guidelines within an effective communication network was
      associated with changes in the management of severely injured children.

PMID- 17016793
TI  - Living donor versus deceased donor liver transplantation for early irresectable
      hepatocellular carcinoma.
AB  - BACKGROUND: Hypothetical studies that favour living donor liver transplantation
      (LDLT) for early hepatocellular carcinoma (HCC) assumed a comparable outcome
      after LDLT and deceased donor liver transplantation (DDLT). The aim of this study
      was to compare the outcome after LDLT with that after DDLT, and to identify
      factors that might account for any differences. METHODS: The study included 60
      patients who met the radiological Milan or University of California at San
      Francisco (UCSF) criteria and underwent LDLT (43 patients) or DDLT (17). RESULTS:
      The LDLT group had fewer incidental tumours and a lower rate of pretransplant
      transarterial chemoembolization but a higher rate of salvage transplantation.
      Waiting time was shorter and graft weight to standard liver weight (GW : SLW)
      ratio was lower in this group. The perioperative course, and histopathological
      tumour size, number, grade and stage were comparable. Median follow-up was 33
      (range 4-120) months. The cumulative 5-year recurrence rate was 29 per cent in
      the LDLT group and 0 per cent in the DDLT group (P = 0.029). A GW : SLW ratio of
      0.6 or less, salvage transplantation, three or more tumour nodules, microscopic
      vascular invasion, and pathological stage beyond the Milan or UCSF criteria were
      significant confounding risk factors. Multivariable analysis identified salvage
      transplantation (relative risk 5.16 (95 per cent confidence interval (c.i.) 1.48
      to 18.02); P = 0.010) and pathological stage beyond the UCSF criteria (relative
      risk 4.10 (95 per cent c.i. 1.02 to 16.48); P = 0.047) as independent predictors
      of recurrence. CONCLUSION: Despite standard radiological selection criteria based
      on number and size, patients who underwent LDLT for HCC had more recurrence
      because of selection bias for other clinical characteristics.

PMID- 17016794
TI  - The responsiveness of the OAB-q among OAB patient subgroups.
AB  - AIMS: Although the majority of patients with overactive bladder (OAB) are
      continent, most patient-reported outcome measures for OAB were designed for
      patients with urinary incontinence. The overactive bladder questionnaire (OAB-q)
      was developed to assess symptom bother and HRQL among both continent and
      incontinent OAB patients; however, the responsiveness of the OAB-q among
      continent patients has not been evaluated. The purpose of this analysis was to
      assess the responsiveness of the OAB-q among OAB patient subgroups with a focus
      on continent patients. METHODS: Post-hoc analyses were conducted from two 12-week
      trials of tolterodine for the treatment of OAB. Patients completed the OAB-q and
      daily bladder diaries (assessing frequency, urgency, and incontinence episodes)
      at baseline, 4 weeks, and 12 weeks. Three patient subgroups were identified on
      the basis of continence status at all three timepoints: (1) continent; (2)
      incontinent; and (3) incontinent at baseline and continent by Week 12 (ITC).
      General linear models were used to compare changes from baseline, and Spearman
      correlations assessed the association between OAB-q changes and bladder diary
      changes. Effect sizes were computed separately for each group. RESULTS: A total
      of 262 continent, 552 incontinent, and 397 ITC patients were included in this
      analysis. Continent patients tended to be younger than incontinent patients, and
      patients were predominantly female, although continent patients had the highest
      percentage of male patients in both studies. Compared with continent patients,
      patients who were incontinent at baseline tended to have greater symptom bother
      and lower HRQL at baseline. All OAB-q change scores were consistently greatest
      for the ITC group (12.1-33.9), and greater for continent patients (10.8-28.6)
      than for incontinent patients (7.6-20.1). All three groups of patients
      experienced reductions in frequency and urgency episodes, and these changes were
      significantly correlated with changes in the OAB-q scales. Among all three
      groups, effect sizes were in the moderate-to-large range for all OAB-q subscales
      except Social Interaction. CONCLUSIONS: The OAB-q is highly responsive to change
      between continent and incontinent patients with OAB, and is a valid tool for
      measuring treatment outcomes among continent OAB patients.

PMID- 17016795
TI  - Systematic review and meta-analysis of methods of diagnostic assessment for
      urinary incontinence.
AB  - AIMS: To evaluate the performance of all tests proposed for the diagnosis of
      urinary incontinence. METHODS: A systematic review and meta-analyses of the
      published literature of methods for diagnostic assessment of urinary
      incontinence. RESULTS: One hundred twenty-one papers were included in the full
      review [Martin et al., 2006]. The quality of reporting in the primary studies was
      poor which reduced the number of studies that could be included in the data
      analysis. The literature suggests that women with urodynamic stress incontinence
      (USI) can be correctly identified in primary care from clinical history alone
      with a sensitivity of 0.92 (95% C.I.: 0.91-0.93) and specificity of 0.56 (0.53
      0.60). A clinical history for the diagnosis of detrusor overactivity (DO) was
      found to be 0.61 (0.57-0.65) sensitive and 0.87 (0.85-0.89) specific. Within
      secondary care imaging of leakage by ultrasound was found to be effective in the
      diagnosis of USI in women with a sensitivity of 0.89 (0.84-0.93) and specificity
      of 0.82 (0.73-0.89). CONCLUSIONS: Clinical interpretation of the results of the
      review is difficult because few studies could be synthesized and conclusions
      made. The published evidence suggests that a large proportion of women with USI
      can be correctly identified in primary care from history alone. Ultrasound offers
      a useful diagnostic tool which could be used prior to, and possibly instead of,
      multi-channel urodynamics in some circumstances. If a patient is to undergo
      urodynamic testing, multi-channel urodynamics is likely to give the most accurate
      result. Further primary studies adhering to STARD guidelines are required on
      commonly used tests.

PMID- 17016797
TI  - Comparison between reduction in 24-hour pad weight, International Consultation on
      Incontinence-Short Form (ICIQ-SF) score, International Prostate Symptom Score
      (IPSS), and Post-Operative Patient Global Impression of Improvement (PGI-I) score
      in patient evaluation after male perineal sling.
AB  - AIMS: We assessed the utility of three self-assessment instruments: the
      International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF),
      the post-operative Patient Global Impression of Improvement (PGI-I) score, and
      the International Prostate Symptom Score (IPSS) by correlating them with an
      objective outcome, the change in 24-hr pad weight, after a male perineal sling.
      METHODS: Twenty-six men with urodynamically confirmed stress incontinence
      underwent a male perineal sling. Patients were evaluated pre-operatively and post
      operatively with a 24-hr pad test, IPSS and ICIQ-SF. Patients also completed the
      PGI-I post-operatively. Changes in study parameters were compared via the paired
      t-test, and correlations were performed using Spearman's rho. RESULTS: There were
      significant reductions in 24-hr pad weight (-274 g, P < 0.001), percentage 24-hr
      pad weight (54.2%), ICIQ-SF score (-6.3, P < 0.001), and the three ICIQ-SF
      subscores (-1.2, -1.7, -3.4 for Questions 3, 4, and 5, respectively, P < 0.001
      for all). The change in total ICIQ-SF score and the post-operative PGI-I score
      correlated strongly with percentage reduction in 24-hr pad weight (r = -0.68, P <
      0.001; r = -0.81, P < 0.001, respectively) and with each other (r = 0.79, P <
      0.001). The change in all three ICIQ-SF subscores correlated significantly with
      percentage reduction in 24-hr pad weight and with post-operative PGI-I score.
      There was no significant change in the IPSS or the voiding or storage subscores,
      and none correlated with any other study parameter. CONCLUSIONS: This study
      validates the construct validity of the ICIQ-SF and PGI-I in the assessment of
      treatment for male stress incontinence and should make clinicians confident in
      comparing studies of incontinence treatment utilizing the change ICIQ-SF score,
      the post-operative PGI-I score, and percentage reduction in 24-hr pad weight as
      outcome measures.

PMID- 17016798
TI  - Does urodynamic investigation improve outcome in patients undergoing prolapse
      surgery?
AB  - AIMS: Without solid evidence, it has been advocated to perform urodynamic
      investigation in all patients scheduled for prolapse surgery. If urodynamic
      investigations were to be valuable in the diagnostic work-up, patients with
      normal and abnormal findings would have different treatment results. Our policy
      to never combine prolapse surgery and stress-incontinence surgery allowed us to
      study whether incontinence after surgery can be predicted from urodynamic
      investigation results. METHODS: A retrospective study was performed in
      consecutive patients undergoing vaginal prolapse surgery (anterior colporraphy
      and/or posterior colporraphy, and/or vaginal hysterectomy) between 2002 and 2004.
      All patients underwent pre-operative urodynamic investigation, including filling
      cystometry, urethral pressure profile measurement, and free flow cystometry. Data
      were collected from the files about medical history, findings at pelvic
      examination, findings at urodynamic investigation and presence of stress- and/or
      urge-incontinence after surgery. RESULTS: We studied 76 patients, of whom 5 (7%)
      patients reported stress-incontinence and 5 (7%) patients reported urge
      incontinence after surgery. Findings at urodynamic investigation could not
      predict the presence of stress- or urge-incontinence after surgery. Likelihood
      ratios (LR) of prior presence of urge and stress-incontinence for the presence of
      post-operative urge- and stress-incontinence were 4.5 and 1.2, respectively. Of
      all findings at urodynamic investigation, only negative transmission during cough
      test was associated with presence of stress-incontinence (LR = 1.5). CONCLUSIONS:
      The prevalence of incontinence after prolapse surgery is low. None of the
      investigated parameters of the urodynamic investigation tests was associated with
      the presence of urinary incontinence after surgery.

PMID- 17016799
TI  - Correlation between urodynamics and perineal ultrasound in female patients with
      urinary incontinence.
AB  - AIMS: We performed urodynamics and perineal ultrasound in female patients with
      urinary incontinence to assess morphology and function of the bladder base
      urethra complex and of the detrusor muscle, and to find the correlation between
      these investigations in the diagnosis of (a) bladder neck and urethral
      hypermobility and (b) detrusor overactivity; we wanted to compare the
      tolerabililty of the urodynamic investigation and of the perineal ultrasound.
      METHODS: We considered 66 female patients referred to our outpatient clinic for
      urinary incontinence; we also studied 14 healthy control patients. After accurate
      case-history collection and physical examination, urodynamic investigation and
      perineal ultrasound were performed, with recording of parameters specific to both
      investigations. The statistical analysis was performed by ANOVA, Bonferroni post
      hoc test, and Spearman correlation test. The tolerability index between the
      diagnostic investigations performed was assessed by a 3-point scale suggested by
      the patient. RESULTS: In patients with stress incontinence the posterior urethro
      vesical angle, the angle of urethral inclination, and the proximal pubo-urethral
      distance are significantly different under stress compared to the resting phase;
      in patients with urge incontinence, the detrusor wall is thicker and is
      accompanied by an increase in opening detrusor pressure and detrusor pressure at
      maximum flow; it is also accompanied by detrusor overactivity with increased
      urethral functional length. Increased urethral functional length is suggested on
      axial US images by alteration of its normal characteristic target-like appearance
      with four concentric rings of different echogenicity. In all cases the
      tolerability of perineal ultrasound has been higher than that of urodynamics.
      CONCLUSIONS: There is a good correlation between urodynamic and perineal
      ultrasound in the diagnosis of bladder neck and urethral hypermobility; perineal
      ultrasound can also be useful in the diagnosis of urge incontinence. Functional
      compressive urethral obstruction can be diagnosed on the basis of the ultrasound
      aspect of the urethral sphincter.

PMID- 17016800
TI  - The molecular basis of urgency: regional difference of vanilloid receptor
      expression in the human urinary bladder.
AB  - AIM: Treatments targeting vanilloid receptor TRPV1 are effective in some bladder
      disorders. Our aim was to determine the expression profiles of TRPV1 in regions
      of human bladder and test the hypothesis that there would be an upregulation of
      TRPV1 in mucosa of patients with bladder hypersensitivity but not idiopathic
      detrusor overactivity (IDO). MATERIALS AND METHODS: Women with sensory urgency
      (SU), interstitial cystitis (IC), and IDO were investigated by videourodynamics
      and cystoscopy. Control biopsies were used for comparison. Biopsies were
      dissected into mucosa and muscle, and evaluated for TRPV1 mRNA expression using
      quantitative competitive RT-PCR (QC-RT-PCR). RESULTS: TRPV1 mRNA from SU trigonal
      mucosa was significantly higher than control trigonal mucosa or SU bladder body
      mucosa. In contrast, in IDO patients, there was no difference between trigonal
      mucosa and body mucosa. In IC biopsies, RNA quality was substandard and unable to
      be used for analysis. The most striking finding was that TRPV1 mRNA expressed in
      SU trigonal mucosa was significantly inversely correlated with the bladder volume
      at first sensation of filling during cystometry. No such relationship was seen
      for IDO trigonal mucosa. No difference was seen in bladder body mucosa from any
      disease groups compared with age-matched control. CONCLUSIONS: The symptoms of SU
      were associated with the increased expression of TRPV1 mRNA in the trigonal
      mucosa. No upregulation or regional differences of TRPV1 mRNA were seen in IDO
      patients. TRPV1 may play a role in SU and premature first bladder sensation on
      filling.

PMID- 17016801
TI  - Neuroimaging H.M.: a 10-year follow-up examination.
AB  - In 1997, Corkin et al. described the anatomical boundaries of the amnesic patient
      H.M.'s surgical resection, based on a comprehensive analysis of magnetic
      resonance imaging (MRI) scans collected in 1992 and 1993 (Corkin et al. (1997) J
      Neurosci 17:3964-3979). We subsequently scanned H.M. on several occasions,
      employing more advanced data acquisition and analysis methods, and now describe
      additional details about his brain anatomy and pathology. This account combines
      results from high-resolution T1-weighted scans, which provide measures of
      cortical and subcortical morphometry, diffusion tensor images, which provide
      quantitative information about white matter microstructure and the anatomy of
      major fasciculi, and T2-weighted images, which highlight damage to deep white
      matter. We applied new MRI analysis techniques to these scans to assess the
      integrity of areas throughout H.M.'s brain. We documented a number of new
      changes, including cortical thinning, atrophy of deep gray matter structures, and
      a large volume of abnormal white matter and deep gray matter signal. Most of
      these alterations were not apparent in his prior scans, suggesting that they are
      of recent origin. Advanced age and hypertension likely contributed to these new
      findings.

PMID- 17016802
TI  - Ultra-performance liquid chromatography/tandem mass spectrometry for the
      simultaneous analysis of aflatoxins B1, G1, B2, G2 and ochratoxin A in beer.
AB  - The simultaneous analysis of aflatoxins B1, G1, B2, G2 and ochratoxin A in beer
      was carried out by ultra-performance liquid chromatography/tandem mass
      spectrometry (UPLC/MS/MS). Mycotoxins were extracted, purified and concentrated
      from the beer sample in one step using a solid-phase extraction (SPE) cartridge
      that contained a polymeric sorbent. Optimization of different parameters, such as
      type of SPE sorbent, type and amount of wash solvent and pH of the sample, was
      carried out. The mobile phase consisted of a gradient of methanol + water (0.1%
      HCOOH) and a reversed-phase C18 column was used for the separation. The mass
      spectrometer used an electrospray ionization source operated in the positive mode
      to detect aflatoxins and in the negative mode to detect ochratoxin. UPLC/MS/MS is
      a rapid and sensitive technique that allows the separation of the five toxins in
      only 3.2 min. The limit of detection is 1 pg.

PMID- 17016803
TI  - Electrospray ionization from a gap with adjustable width.
AB  - In this paper, we present a new concept for electrospray ionization mass
      spectrometry, where the sample is applied in a gap which is formed between the
      edges of two triangular-shaped tips. The size of the spray orifice can be changed
      by varying the gap width. The tips were fabricated from polyethylene
      terephthalate film with a thickness of 36 microm. To improve the wetting of the
      gap and sample confinement, the edges of the tips forming the gap were
      hydrophilized by means of silicon dioxide deposition. Electrospray was performed
      with gap widths between 1 and 36 microm and flow rates down to 75 nL/min. The gap
      width could be adjusted in situ during the mass spectrometry experiments and
      nozzle clogging could be managed by simply widening the gap. Using angiotensin I
      as analyte, the signal-to-noise ratio increased as the gap width was decreased,
      and a shift towards higher charge states was observed. The detection limit for
      angiotensin I was in the low nM range.

PMID- 17016804
TI  - Selectivity of electrospray response in small polymer analysis by mass
      spectrometry.
AB  - The selectivity of electrospray was explored for a small poly(ethylene)glycol by
      comparing the oligomer response obtained from direct polymer introduction in flow
      injection analysis with the signal recorded in high-performance liquid
      chromatography/mass spectrometry (HPLC/MS). When the oligomer mixture was
      ionized, a suppression effect was measured for all but the more hydrophobic
      congeners for which the response was enhanced. This result would reflect the
      influence of electrospray droplet chemical composition on the equilibrium
      partitioning coefficient in Enke's model. On average, the electrospray
      selectivity observed for the studied poly(ethylene)glycol did not affect the
      molecular weight distribution parameters as response for the most concentrated
      oligomers was suppressed to the same extent while over-expressed largest
      congeners had a low contribution to the total polymer sample.

PMID- 17016805
TI  - Rapid and sensitive determination of donepezil in human plasma by liquid
      chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
AB  - A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed
      and validated for the determination of donepezil in human plasma samples.
      Diphenhydramine was used as the internal standard. The collision-induced
      transition m/z 380 --> 91 was used to analyze donepezil in selected reaction
      monitoring mode. The signal intensity of the m/z 380 --> 91 transition was found
      to relate linearly with donepezil concentrations in plasma from 0.1-20.0 ng/mL.
      The lower limit of quantification of the LC/MS/MS method was 0.1 ng/mL. The intra
      and inter-day precisions were below 10.2% and the accuracy was between -2.3% and
      +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in
      which healthy Chinese volunteers each received a single oral dose of 5 mg
      donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to
      fit the donepezil plasma concentration-time curve. Maximum plasma concentration
      was 12.3 +/- 2.73 ng/mL which occurred at 3.50 +/- 1.61 h post-dosing. The
      apparent elimination half-life and the area under the curve were, respectively,
      60.86 +/- 12.05 h and 609.3 +/- 122.2 ng . h/mL. LC/MS/MS is a rapid, sensitive
      and specific method for determining donepezil in human plasma samples.

PMID- 17016806
TI  - Identification of sources and production processes of bottled waters by stable
      hydrogen and oxygen isotope ratios.
AB  - Bottled water is a food product that considerably depends on the environment from
      which it originates, not only at the place where it is produced, but
      predominantly on the conditions in the recharge area of the wells captured for
      bottling. According to their source and the bottling process, bottled waters can
      be divided into natural and artificially sparkling waters, still and flavoured
      waters. These waters originate from various parts of the hydrological cycle and
      their natural origin is reflected in their hydrogen and oxygen stable isotopic
      compositions (delta(2)H and delta(18)O). A total of 58 domestic and foreign
      brands and 16 replicates of bottled waters, randomly collected on the Slovene
      market in September 2004, were analysed for delta(2)H and delta(18)O. The
      isotopic composition varied between -83 per thousand and -46 per thousand with an
      average of -66 per thousand for hydrogen, and between -11.9 per thousand and -7.5
      per thousand with an average of -9.6 per thousand for oxygen. This investigation
      helped (1) to determine and test the classification of bottled waters, (2) to
      determine the natural origin of bottled water, and (3) to indicate differences
      between the natural and production processes. The production process may
      influence the isotopic composition of flavoured waters and artificially sparkling
      waters. No such modification was observed for still and natural sparkling waters.
      The methods applied, together with hydrological knowledge, can be used for the
      authentication of bottled waters for regulatory and consumer control
      applications.

PMID- 17016807
TI  - Directional asymmetry of pelvic vestiges in threespine stickleback.
AB  - Extensive reduction of the size and complexity of the pelvic skeleton (i.e.,
      pelvic reduction) has evolved repeatedly in Gasterosteus aculeatus. Asymmetrical
      pelvic vestiges tend to be larger on the left side (i.e., left biased) in
      populations studied previously. Loss of Pitx1 expression is associated with
      pelvic reduction in G. aculeatus, and pelvic reduction maps to the Pitx1 locus.
      Pitx1 knockouts in mice have reduced hind limbs, but the left limb is larger.
      Thus left-biased directional asymmetry of stickleback pelvic vestiges may
      indicate the involvement of Pitx1 in pelvic reduction. We examined 6,356
      specimens from 27 Cook Inlet populations of G. aculeatus with extensive pelvic
      reduction. Samples from 20 populations exhibit the left bias in asymmetrical
      pelvic vestiges expected if Pitx1 is involved, and three have a slight, non
      significant left bias. However, samples from three populations have a significant
      right bias, and one large sample from another population has equal frequencies of
      specimens with larger vestiges on the left or right side. A sample of fossil
      threespine stickleback also has significantly left-biased pelvic vestiges. These
      results suggest that silencing of Pitx1 or the developmental pathway in which it
      functions in the pelvis is the usual cause of pelvic reduction in most Cook Inlet
      populations of G. aculeatu, and that it caused pelvic reduction at least 10
      million years ago in a stickleback population. A different developmental genetic
      mechanism is implicated for three populations with right-biased pelvic vestiges
      and for the population without directional asymmetry.

PMID- 17016808
TI  - The subplacenta in Octodon degus and Petromus typicus--two hystricognath rodents
      without significant placental lobulation.
AB  - Until now, defining characters of hystricognath rodents have been the subplacenta
      and the lobulation of the main chorioallantoic placenta. However, recent studies
      have revealed hystricognaths without marked lobulation, which is a plesiomorphic
      condition of the group. The question thus arises whether the subplacenta of these
      taxa is structurally homologous to that of other hystricognaths. Therefore,
      subplacental morphology and ontogeny were investigated in Octodon and Petromus by
      conventional light and electron microscopy, and the stem species pattern of
      Hystricognathi was reconstructed by applying MacClade. The subplacentae of both
      species share important similarities with other hystricognaths. The organ
      develops early in gestation but degenerates towards term. It consists of folded
      layers of cellular and syncytial trophoblast, the latter enclosing maternal blood
      lacunae and electron-dense particles. Root-like syncytial outgrowths (syncytial
      streamers) and extraplacental trophoblast cells occur at the lateral and basal
      borders of the organ. Maternal vascularisation by blood lacunae within the
      subplacental syncytiotrophoblast is acquired early but lost during mid-gestation.
      Vascularisation by fetal vessels is established later. Fetomaternal exchange via
      blood circulation inside the subplacenta is unlikely to occur, since periods of
      maternal and fetal vascularisation show little overlap. In conclusion, the
      subplacentae of both species are regarded as homologous to other hystricognaths,
      comprising 18 character conditions that belong to their stem species pattern.
      Thus, the systematic unity of the group can be confirmed.

PMID- 17016809
TI  - Electron capture dissociation mass spectrometry of peptide cations containing a
      lysine homologue: a mobile proton model for explaining the observation of b-type
      product ions.
AB  - Eleven doubly protonated peptides with a residue homologous to lysine were
      investigated by electron capture dissociation mass spectrometry (ECD-MS). Lysine
      homologues provide the unique opportunity to examine the ECD fragmentation
      behavior by allowing us to vary the length of the lysine side chain, with minimal
      structural change. The lysine homologue has a primary amine side chain with a
      length that successively decreases by one methylene (CH(2)) unit from the -
      CH(2)CH(2)CH(2)CH(2)NH(2) of lysine and the accompanying decrease of its proton
      affinities: lysine (K), 1006.5(+/-7.2) kJ/mol; ornithine (K(*)), 1001.1(+/-6.6)
      kJ/mol; 2,4-diaminobutanoic acid (K(**)), 975.8(+/-7.4) kJ/mol; 2,3
      diaminopropanoic acid (K(***)), 950.2(+/-7.2) kJ/mol. In general, the lysine
      homologous peptides exhibited overall ECD fragmentation patterns similar to that
      of the lysine-containing peptides in terms of the locations, abundances, and ion
      types of products, such as yielding c(+) and z(+.) ions as the dominant product
      ions. However, a close inspection of product ion mass spectra showed that ECD-MS
      for the alanine-rich peptides with an ornithinyl or 2,4-diaminobutanoyl residue
      gave rise to b ions, while the lysinyl-residue-containing peptides did not, in
      most cases, produce any b ions. The peptide selectivity in the generation of b(+)
      ions could be understood from within the framework of the mobile proton model in
      ECD-MS, previously proposed by Cooper (Ref. 29). The exact mass analysis of the
      resultant b ions reveals that these b ions are not radical species but rather the
      cationic species with R-CO(+) structure (or protonated oxozalone ion), that is,
      b(+) ions. The absence of [M+2H](+.) species in the ECD mass spectra and the
      selective b(+)-ion formation are evidence that the peptides underwent H-atom loss
      upon electron capture, and then the resulting reduced species dissociated
      following typical MS/MS fragmentation pathways. This explanation was further
      supported by extensive b(+) ions generated in the ECD of alanine-based peptides
      with extended conformations.

PMID- 17016811
TI  - Damages and rewards: assessment of malingered disorders in compensation cases.
AB  - The assessment of malingering poses unique challenges to forensic practitioners
      in compensation cases and disability determinations. Beyond malingering itself,
      false claims can be presented regarding both the source of genuine symptoms and
      their injurious effects on work and social functioning. The article examines how
      contextually based psychological factors can affect clients' presentation in
      compensation cases. Important distinctions between different types of response
      style (e.g. malingering, feigning, and secondary gain) are presented. In
      addition, empirically validated detection strategies provide a clinical framework
      for the assessment of feigned disorders. With an emphasis on compensation cases
      and clinically relevant disorders, the effectiveness of these detection
      strategies is considered for specific psychological measures.

PMID- 17016812
TI  - Investigating the M-FAST: psychometric properties and utility to detect
      diagnostic specific malingering.
AB  - This study examined the ability of the M-FAST to differentiate a group of
      undergraduate students simulating one of four DSM-IV diagnoses (n = 190;
      schizophrenia, major depressive disorder, bipolar disorder, and posttraumatic
      stress disorder) and a clinical comparison sample drawn from previous M-FAST
      studies comprising individuals with the same diagnosis (n = 142). Across all
      diagnostic conditions, the simulators obtained higher M-FAST total scores than
      the clinical comparisons, and the rare combinations scale was equal or superior
      to the total score at differentiating the groups. The M-FAST was most efficient
      at distinguishing feigned from bona fide schizophrenia. Although the internal
      consistency of the total score was high (alpha = 0.88), inter-item correlations
      were lower than values reported in previous research. Lastly, given the
      importance of base rate considerations in the evaluation of diagnostic
      instruments, it was notable that the M-FAST was able to identify malingerers even
      at relatively low base rates.

PMID- 17016813
TI  - Adults' ability to detect children's lying.
AB  - Adults are poor deception detectors when examining lies told by adults, on
      average. However, there are some adults who are better at detecting lies than
      others. Children learn to lie at a very young age, a behavior that is socialized
      by parents. Yet, less is known about the ability to detect children's lies,
      particularly with regard to individual differences in the ability to detect this
      deception. The current study explored adult raters' ability to discern honesty in
      children who lied or told the truth about committing a misdeed. Results showed
      that adults are no better at detecting children's lies than they are with adult
      lies. In particular, adults were very poor at identifying children's honest
      statements. However, individual differences did emerge, suggesting that the
      ability to detect lying in children might be facilitated by relevant experience
      working with children. Implications for legal and mental health contexts are
      discussed.

PMID- 17016815
TI  - Introduction to this issue: malingering.

PMID- 17016816
TI  - Long-term effects of immunotoxic cholinergic lesions in the septum on acquisition
      of the cone-field task and noncognitive measures in rats.
AB  - In rats, nonspecific mechanical or neurotoxic lesions of the septum impair
      spatial memory in, e.g., Morris water- and radial-maze tasks. Unfortunately, the
      lack of specificity of such lesions limits inferences about the role of the
      cholinergic hippocampal projections in spatial cognition. We therefore tested the
      effects of septal lesions produced by 192 IgG-saporin in rats, which is highly
      selective for basal forebrain cholinergic neurons, on home cage activity,
      noncognitive tests (modified Irwin test, open field and forced swimming tests,
      and various sensorimotor tasks), and the cone-field spatial learning task. The
      immunotoxic lesion reduced acetylcholine (ACh) levels in the septum (-61%) and
      hippocampus (>-75%). Rats with lesions showed mild home-cage hyperactivity at 4
      weeks postlesion, but no noncognitive deficits at 13 weeks postsurgery. In the
      cone-field task, rats with septal lesions made more working- and reference-memory
      errors than the controls, but acquisition curves were parallel in both groups.
      The speed of visiting cones was faster in the rats with lesions, indicative of
      disturbed attention or increased motivation. These data support the growing
      evidence that involvement of the septohippocampal cholinergic system in spatial
      learning and memory may have been overestimated in studies that used lesions with
      poor selectivity.

PMID- 17016817
TI  - Developmental switch from LTD to LTP in low frequency-induced plasticity.
AB  - The stimulation of the Schaffer collateral/commissural fibers at low frequency (1
      Hz) for 3-5 min can trigger a slow-onset form of low-frequency stimulation (LFS)
      long-term potentiation (LTP) (LFS-LTP) in the CA1 area of the adult rat
      hippocampus. Here we have examined the developmental profile of this plasticity.
      In 9-15 day-old rats, the application of 1 Hz for 5 min induced long-term
      depression (LFS-LTD). In 17-21 day-old rats, 1 Hz stimulation had no effect when
      applied for 5 min but mediated LTD when stimulus duration was increased to 15
      min. Over 25 day-old, 1 Hz stimulation mediated LFS-LTP. LFS-LTD was dependent on
      both N-methyl-D-aspartate (NMDA) and mGlu5 receptor activation. Antagonists of
      mGlu1alpha and cannabinoid type 1 receptor were ineffective to block LTD
      induction. LFS-LTD was not associated with a change in paired-pulse facilitation
      ratio, suggesting a postsynaptic locus of expression of this plasticity. Next, we
      examined whether LFS-LTD was related to 'chemical' LTDs obtained by the direct
      stimulation of mGlu5 and NMDA receptors. The saturation of LFS-LTD completely
      occluded NMDA- and (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG)-induced LTD. CHPG
      LTD and NMDA-LTD occluded each other. In addition, we observed that NMDA-LTD was
      dependent on mGlu5 receptor activation in 9-12 day old rats while it was not in
      animals older than 15 day-old. Therefore we postulate that during LFS
      application, NMDA and mGlu5 receptor could interact to trigger LTD. Low-frequency
      mediated synaptic plasticity is subject to a developmental switch from NMDA- and
      mGlu5 receptor-dependent LTD to mGlu5 receptor-dependent LTP with a transient
      period (17-21 day-old) during which LFS is ineffective.

PMID- 17016818
TI  - The subiculum comes of age.
AB  - The subiculum has long been considered as a simple bidirectional relay region
      interposed between the hippocampus and the temporal cortex. Recent evidence,
      however, suggests that this region has specific roles in the cognitive functions
      and pathological deficits of the hippocampal formation. A group of 20 researchers
      participated in an ESF-sponsored meeting in Oxford in September, 2005 focusing on
      the neurobiology of the subiculum. Each brought a distinct expertise and approach
      to the anatomy, physiology, psychology, and pathologies of the subiculum. Here,
      we review the recent findings that were presented at the meeting.

PMID- 17016819
TI  - Do tests of malingering concur? Concordance among malingering measures.
AB  - Malingering test accuracy is increasingly a major issue in psychology and law.
      Integrating results across measures might offset limitations of a single test,
      but the practical benefits of using several tests depend on the extent to which
      they misclassify the same individuals. Data from 66 evaluatees were used to
      assess the degree of overlap and consistency of classification among several
      commonly used malingering instruments. Although correlative data indicated that
      measures were highly redundant even across symptom domains, classification
      accuracy analyses revealed that findings based on conjunctions of these scales
      may not overlap to the degree that the correlations might suggest.

PMID- 17016820
TI  - From flawed self-assessment to blatant whoppers: the utility of voluntary and
      involuntary behavior in detecting deception.
AB  - Malingering occupies a range on a continuum from biased self-perception to
      conscious, deliberate, serious lies. One aspect of this continuum is the element
      of self-conscious or deliberate control. Suggestions from Darwin's writings
      concerning the role of voluntary and involuntary activation of the facial muscles
      are examined and illustrated with data from a 40 year program of research on
      deception. The impact of the voluntary-involuntary distinction on the appearance,
      timing, symmetry and cohesion of facial expressions of emotion is explained. Data
      relevant to changes in vocal and gestural aspects of demeanor in honest and
      deceptive behavior are also reviewed. The relevance of these laboratory-based
      findings on the voluntary control of nonverbal behavior in assessing some types
      of malingering is discussed.

PMID- 17016821
TI  - HLA-class II haplotype associations with ovarian cancer.
AB  - The development of cancer is a multistep process that is characterized by the
      accumulation of genetic alterations in cells and changed cellular interactions
      with the surrounding healthy tissues. The human immune system is believed to be
      intrinsically involved in this process. The correlation of certain human
      leukocyte antigen (HLA)-class I and II haplotypes with tumorigenesis is
      documented in a variety of tumors. However, few data exist on the possible
      association of specific HLA-class II alleles or haplotypes with ovarian cancer.
      In our sample of 52 Caucasian patients with primary ovarian carcinoma and 239
      female healthy local controls, we observed a significantly increased incidence of
      the HLA-class II haplotypes DRB1*0301 - DQA1*0501 - DQB1*0201 (p < 0.001) and
      DRB1*1001 - DQA1*0101 - DQB1*0501 (p < 0.001) in the patients. Our data suggest
      that HLA-class II loci or individual HLA-class II haplotypes may be involved in
      the pathogenesis of ovarian cancer.

PMID- 17016822
TI  - No major impact of mammography screening on the age specific incidence rates of
      breast cancer in the Netherlands.

PMID- 17016823
TI  - Origins and consequences of centrosome aberrations in human cancers.
AB  - Recent years have seen a revival of interest in the possible contribution of
      centrosomes to the development of human cancers. The underlying hypothesis,
      formulated almost 100 years ago (Boveri T. The origin of malignant tumors;
      Baltimore, MD: Williams and Wilkins, 1929.), states that numerical and/or
      structural centrosome abnormalities will cause chromosome [corrected]
      missegregation. In addition, centrosome abnormalities are expected to affect cell
      shape, polarity, and motility. Thus, deregulation of centrosome number and
      function may foster both chromosomal instability and loss of tissue architecture-
      2 of the most common phenotypes associated with solid human tumors. In support of
      the role of centrosome deregulation in tumorigenesis, centrosome aberrations have
      been observed in early, premalignant lesions. Moreover, they are frequent in many
      different types of common tumors and their prominence often correlates with poor
      clinical outcome. This review addresses the origins of centrosome aberrations in
      human tumors as well as the expected impact of centrosome aberrations on cell
      fate and tumor development.

PMID- 17016824
TI  - Lifetime adult weight gain, central adiposity, and the risk of pre- and
      postmenopausal breast cancer in the Western New York exposures and breast cancer
      study.
AB  - While there are quite consistent data regarding associations of body weight and
      postmenopausal breast cancer, there are now accumulating data that would indicate
      that weight gain in adult life is more predictive of risk than absolute body
      weight. There is, however, little known about the relative impact of timing of
      weight gain in adult life as well as other characteristics of the weight and
      breast cancer association that might provide insight into the mechanism of the
      observation. We conducted a population-based case control study of breast cancer
      (1996-2001), the Western New York Exposures and Breast Cancer Study. Included
      were 1,166 women with primary, histologically confirmed, incident breast cancer
      and 2,105 controls frequency-matched on age, race and county of residence.
      Unconditional logistic regression was used to estimate odds ratios and 95%
      confidence intervals. We found increased risk of breast cancer associated with
      lifetime adult weight gain among post- but not premenopausal women, and there was
      a 4% increase in risk for each 5 kg increase in adult weight. Further there was a
      tendency toward a stronger association for those with higher waist circumference
      and those with positive estrogen or progesterone status, and who had never used
      HRT. We also found an association with risk for weight gain since first pregnancy
      and for weight gain between the time of the first pregnancy and menopause,
      independent of body mass index and lifetime adult weight gain. Our results
      suggest that there are time periods of weight gain that have greater impact on
      risk, and that central body fat, receptor status and hormone replacement therapy
      may all affect the observed association.

PMID- 17016825
TI  - Leukemia-associated antigenic isoforms induce a specific immune response in
      children with T-ALL.
AB  - The potential immunogenicity of acute lymphoblastic leukemia of the T cell (T
      ALL), a small subgroup of childhood leukemia with increased risk for treatment
      failure and early relapse, was addressed by serological identification of
      leukemia-derived antigens by recombinant expression cloning (SEREX). Thirteen
      antigens with homology to known genes that are involved in critical cellular
      processes were detected. Further characterization of the 4 novel isoforms
      revealed that 3 (HECTD1Delta, CX-ORF-15Delta and hCAP-EDelta) had restricted mRNA
      expression in more than 70% of T-ALLs (n = 22) and that specific antibodies
      against these isoforms were detected in up to 30% of patients (n = 16), with the
      highest frequency for HECTD1Delta. The latter protein was present at high
      abundance in T-ALLs but not in normal hematopoietic tissues. Given that the
      leukemia-associated antigens detected in this study have an intracellular
      localization, the generation of immune effector responses most likely requires
      antigen presentation. To test this assumption, dendritic cells were loaded with
      HECTD1Delta protein and used for T cell stimulation. A specific T cell response
      was induced in vitro in all 3 healthy donors studied, including a former T-ALL
      patient. These data suggest that T-ALL may induce a specific cellular and humoral
      antileukemia immune response in children, thereby supporting new approaches for
      immunotherapy.

PMID- 17016826
TI  - Helicobacter pylori infection appears the prime risk factor for stomach cancer.

PMID- 17016827
TI  - Laser-assisted microdissection (LAM) in developmental biology.
AB  - The analysis of gene expression in developing organs is a valuable tool for the
      assessment of genetic fingerprints during the various stages of differentiation.
      Complex processes in developing tissues are particularly difficult to understand
      in terms of biochemical phenomena. Laser-assisted microdissection (LAM) allows
      the efficient and precise capture of cells or groups of cells from developing
      tissues in sufficient quantities and within the context of time and space to
      permit the subsequent molecular characterization of the targeted tissue. The
      technique development has dramatically increased the ease of isolating specific
      cells which, together with progress in tissue preparation and microextraction
      protocols, allows for broad-range down-stream applications in the fields of
      genomics, transcriptomics and proteomics. This review gives an overview of the
      LAM technology and its application in developmental biology.

PMID- 17016828
TI  - The use of evolutionary biology concepts for genome annotation.
AB  - The past decade has seen the completion of numerous whole-genome sequencing
      projects, began with bacterial genomes and continued with eukaryotic species from
      different phyla: fungi, plants and animals. Besides, more biological information
      are produced and are shared thanks to information exchange systems, and more
      biological concepts, as well as more bioinformatics tools, are available. In this
      article, we will describe how the evolutionary biology concepts, as well as
      computer science, are useful for a better understanding of biology in general and
      genome annotation in particular. The genome annotation process consists of taking
      the raw DNA produced, for example, by the genome sequencing projects, adding the
      layers of analysis and interpretation necessary to extract its biological
      significance and placing it in the context of our understanding of biological
      processes. Genome annotation is a multistep process falling into two broad
      categories: structural and functional annotation.

PMID- 17016829
TI  - Relationship among respondent ethnicity, ethnic identity, acculturation, and
      homeless status on a homeless population's functional status.
AB  - This study investigated the relationship of homeless status, ethnic identity,
      respondent ethnicity (African American, Latino, Native American, and Anglo), and
      Latino, Anglo, and Mexican American orientation on the functional impairment
      (Behavior and Symptom Identification Scale, BASIS-32; S. V. Eisen, 1996) of 355
      homeless men and women who were interviewed in Pomona, California. Multivariate
      analyses of variance results indicated that respondent ethnicity was related to
      several BASIS-32 subscales. Specifically, Anglo and African American homeless
      adults had greater functional impairment than did Latino or Native American
      respondents. In addition, high Anglo orientation among chronically homeless
      Latino respondents, with low ethnic identity was associated with higher levels of
      functional impairment on the BASIS-32 Psychosis subscale. The implications of
      these findings are discussed.

PMID- 17016830
TI  - Alexithymia and interpersonal problems.
AB  - This study examines whether alexithymia relates to specific interpersonal
      problems, based on data collected in a sample of mental health outpatients (N =
      404) and a student sample (N = 157). Linear regression analysis, in which the
      effects of group, gender, and age were controlled, indicated that two
      interpersonal problems were significantly and reliably related to alexithymia:
      cold/distant and nonassertive social functioning. The theoretical relevance of
      the results for attachment and psychoanalytic theory is indicated, as well as
      implications of the findings for clinical practice.

PMID- 17016831
TI  - Atmospheric-pressure Penning ionization of aliphatic hydrocarbons.
AB  - A study has been made of the atmospheric-pressure Penning ionization (APPeI) of
      aliphatic hydrocarbons (pentane, hexane, heptane, and octane) with long-lived
      rare gas atoms (Rg*). The metastable rare gas atoms (He*, Ne*, Ar* and Kr*) were
      generated by the negative-mode corona discharge of atmospheric-pressure rare
      gases. In the Rg*APPeI mass spectra for aliphatic hyrocarbons, the relative
      abundances of fragment ions were found to increase in the order of He* --> Ne* -
      > Ar* --> Kr*. The order is in the opposite direction to the internal energies of
      the Rg*. The less fragmentation observed for He* may be because the nascent
      molecular ions [M(+.)]* formed by Penning ionization have lifetimes long enough
      for them to be collisionally deactivated in the atmospheric-pressure ion source.
      It was found that the relative abundances of fragment ions in Ar*APPeI increased
      when the sample pressure in the ion source was reduced. This is attributed to the
      collision of Ar* with molecular ions followed by fragmentation.

PMID- 17016832
TI  - Usefulness of an integrated microfluidic device (HPLC-Chip-MS) to enhance
      confidence in protein identification by proteomics.
AB  - Nanoflow liquid chromatography/mass spectrometry (nanoLC/MS) has become a current
      tool in proteomics applications increasingly used in the search for new
      biomarkers. A new integrated microfluidic device (HPLC-Chip), coupled to ion trap
      mass spectrometry (ITMS), appears as an innovative and robust tool for improving
      the identifications commonly performed by nanoLC/MS/MS. We tested this device for
      the identification of proteins obtained from two-dimensional gel electrophoresis
      or chromatography. The chip allows the measurement of reproducible retention
      times that, in association with m/z ratios, was found useful for identifying
      peptide sequences without ambiguity. A sensitivity increase of a factor of at
      least 5-fold is obtained compared to the results obtained previously in our
      laboratory by conventional nanoLC/MS/MS on the same ion trap. We conclude that
      this recently available microfluidic device can be a valuable tool during
      biomarker discovery programs, particularly identifying low-abundance proteins.

PMID- 17016833
TI  - After two decades a second anchor for the VPDB delta13C scale.

PMID- 17016834
TI  - Early handling reduces vulnerability of rats to activity-based anorexia.
AB  - Resistance to restricted feeding with and without wheel access was tested in rats
      handled (H) for 20 days since birth. Weight loss produced by 1.5-hr restricted
      food access was less in H than in non-handled (NH) males when tested aged 41
      days. At this age combining food restriction with access to a running wheel (a
      procedure commonly known as activity-based anorexia, ABA) produced very rapid
      weight loss and no effect of handling was detected. When 75-day females were
      tested in the same way, under the ABA procedure H rats took longer than NH
      controls to reach the removal criterion. Simply restricting food access in these
      females produced variable weight loss, without detection of any handling effect.
      No differences in food intake or running were detected between H and NH rats in
      either males or females. In conclusion, handling seems to have a direct effect on
      rats' later response to either food deprivation alone or to an ABA procedure.

PMID- 17016835
TI  - Long-term impact of early olfactory experience on later olfactory conditioning.
AB  - This study examined the duration of the effect of early olfactory experience in
      rats by determining the ease of conditioning and then reconditioning to an early
      experienced odor. Rat pups (experimental group) were exposed to aniseed odor
      sprayed on the mother's belly from day 1 to 20 after birth. A control group was
      exposed only to water. At the ages of 21 and 40 days all the rats (experimental
      and control) were tested for preference for the odor of aniseed. Starting from
      day 41 after birth they were conditioned in a Y-maze to approach the odor of
      aniseed for a reward. We then divided both groups into five subgroups each. Each
      subgroup was retrained to approach aniseed after 5, 6, 7, 8 or 9 months, and
      their speeds of reconditioning to the odor were compared. The results showed that
      all rats in the early exposed group had remembered the odor and did not require
      reconditioning, unlike those in the group that had not had the early olfactory
      conditioning. The effect of the early experience was still detectable at least 5
      months after last exposure to the odor.

PMID- 17016836
TI  - Development of individually distinct recognition cues.
AB  - Despite extensive research on the functions of kin recognition, little is known
      about ontogenetic changes in the cues mediating such recognition. In Belding's
      ground squirrels, Spermophilus beldingi, secretions from oral glands are both
      individually distinct and kin distinct, and function in social recognition across
      many contexts. Behavioral studies of recognition and kin preferences suggest that
      these cues may change across development, particularly around the time of weaning
      and emergence from natal burrows (around 25 days of age). I used an habituation
      discrimination task with captive S. beldingi, presenting subjects with odors
      collected from a pair of pups at several ages across early development. I found
      that at 21 days of age, but not at 7 or 14, young produce detectable odors. Odors
      are not individually distinct, however, until 28 days of age, after young have
      emerged from their burrows and begun foraging. In addition, an individual's odor
      continues to develop after emergence: odors produced by an individual at 20 and
      40 days of age are perceived as dissimilar, yet odors produced at 28 and 40 days
      are treated as similar. Developmental changes in odors provide a proximate
      explanation for why S. beldingi littermate preferences are not consolidated until
      after natal emergence, and demonstrate that conspecifics must update their
      recognition templates as young develop.

PMID- 17016837
TI  - In uniparental Phodopus sungorus, new mothers, and fathers present during the
      birth of their offspring, are the only hamsters that readily consume fresh
      placenta.
AB  - Placentophagia is common among parturient female mammals but non-parturient
      females generally refuse placenta. Biparental male dwarf hamsters (Phodopus
      campbelli) readily consume placenta. The present study quantified placentophagia
      and liver acceptance in the closely related Siberian hamster P. sungorus in which
      males do not participate in the birth and are not responsive to a displaced pup.
      Sexually naive P. sungorus males and females refused both placenta and liver (all
      groups <10%). Reproductive females specifically consumed placenta on the day
      before (G17), and the day of, parturition (G18) (>80%). Males rejected both
      tissues on G17 and accepted placenta soon after the birth (G18) (80%) only if
      they were present during the birth. Palatability of the placenta was not
      responsible for the species difference as P. campbelli accepted P. sungorus
      placenta. Results are consistent with a neophobic reaction to both placenta
      (conspecific or heterospecific) and liver as P. sungorus also rejected P.
      campbelli placenta.

PMID- 17016838
TI  - Maternal care patterns and behavioral development of rhesus macaque abused
      infants in the first 6 months of life.
AB  - We investigated the maternal care patterns of rhesus macaque mothers who
      physically abuse their infants, and compared their infants' behavior to that of
      nonabused infants. Parametric and multidimensional scaling analyses indicated
      that abusive mothers have a distinct parenting style characterized by high rates
      of rejection and contact-breaking from their infants. Compared to control
      infants, abused infants exhibited signs of delayed independence from their
      mothers including higher rates of distress calls and anxiety, lower rates of
      contact-breaking, and differences in play. Several aspects of the abused infants'
      behavior were correlated with rates of abuse received during the first month, or
      with other maternal behaviors. These findings provide a more comprehensive
      characterization of the parenting styles of abusive mothers and the early
      behavioral development of their infants than previously available. Detailed
      knowledge of the early experience of abused infants is crucial for understanding
      possible pathological alterations in behavior and neuroendocrine function later
      in life.

PMID- 17016839
TI  - Head-cocking as a form of exploration in the common marmoset and its development.
AB  - Head-cocking of 15 infant marmosets (Callithrix jacchus) was scored from Day 1 to
      60 of postnatal life, the growth period with overproduction of interneuronal
      synapses. Head-cocking was scored during four 30 min intervals daily, including
      angle of head-cocking and objects being fixated. Mean age of onset of head
      cocking was Day 13 (+/-1.3) and frequency increased to a fixed rate by Day 24-29,
      at the time of maturation of the foveal representation in layer 6 of the visual
      cortex, thus lending further support to the importance of head-cocking to visual
      processing. The most common distance of objects fixated during head-cocking was
      up to .5 m. Angle of head-cocking increased with age, and some asymmetry of
      direction was noted. Fewer head-cocking events occurred in the morning than in
      the afternoon. We also scored anogenital licking of offspring. Head-cocking
      occurred at higher levels in marmosets receiving more anogenital licking. As this
      was associated positively with increased exploration, head-cocking may be
      regarded as an exploratory behavior.

PMID- 17016840
TI  - Effects of human contact and vagal regulation on pain reactivity and visual
      attention in newborns.
AB  - In two experiments we examined the effects of human contact and vagal regulation
      on newborns' pain reactivity and visual attention. Baseline cardiac vagal tone
      was measured during quiet sleep and during the experiment, and vagal withdrawal
      was indexed as change in vagal tone from baseline to pain (study 1) or attention
      (study 2). In study 1, 62 healthy newborns were videotaped during a heel-prick
      procedure and pain reactivity was assessed from micro-level coding of facial
      expressions, cry behavior, and body movements. Infants were randomly assigned to
      a contact condition, held by a female assistant, or a no contact condition, on an
      infant-seat in a similar angle. In study 2, 62 additional healthy newborns,
      randomly assigned to contact and noncontact conditions, were presented with 2
      visual stimuli for a 60 s familiarization period, which were then paired with a
      novel stimulus. Visual interest, alertness, and novelty preference were coded.
      Human contact had no effect on the newborns' pain response. Visual attention
      increased with human contact and newborns in the contact condition looked at the
      stimuli more frequently, with higher alertness, for longer durations, and had a
      higher novelty preference. Autonomic reactivity-as indexed by vagal withdrawal
      differentiated newborns with intense and mild pain response. Discussion focused
      on proximity to conspecifics as a contributor to emerging regulatory and adaptive
      functioning in the human infant.

PMID- 17016841
TI  - Glucose enhances newborn memory for spoken words.
AB  - The effect of a 2 g/kg glucose feed was compared with a water feed on retention
      of a spoken word in 2-4 days old infants in a between group randomized trial.
      Infants heard a word in 30-s trials until they demonstrated orientation (head
      turns towards the sound) and habituation. After a 100 s delay, infants who
      received glucose turned toward the word less often than infants receiving water
      (means 31.8 vs. 57.7%, t = 2.8, p < 0.01) implying that they remembered the word
      better. There were no differences between groups in measures of attention to or
      rate of learning of the word. Only infants who subsequently oriented towards a
      different word, indicating that they remained alert, were used in the data
      analysis. The results suggest that glucose enhanced memory for a spoken word in
      neonates.

PMID- 17016844
TI  - Urethral pressure reflectometry; a novel technique for simultaneous recording of
      pressure and cross-sectional area in the female urethra.
AB  - AIMS: Urethral pressure reflectometry (UPR) is a new and easily applicable
      technique for simultaneous measurements of cross-sectional area (CA) and pressure
      in the urethra. CAs of 1-16 mm(2) and pressures of 0-200 cm H(2)O can be measured
      along the entire urethra in the same setting. The method is reliable in vitro.
      The aim was to present the method and some clinical results from the female
      urethra. METHODS: A very thin polyurethane-bag was placed in the urethra. A pump
      applied preselected pressures stepwise to the bag. For every step the CA was
      measured by acoustic reflectometry. Measurements were made both during inflation
      and deflation. The women were examined in different positions and with different
      provocations. RESULTS: UPR was easy to perform. The obtained parameters were
      opening pressure, closing pressure, elastance of the opening curve and closing
      curve, and hysteresis. CONCLUSIONS: UPR is feasible for measuring urethral
      pressure and corresponding CA. The technique is minimally invasive and with
      minimal impact on the urethra per se. The technique provides physiological sound
      parameters which add potentially important physiological/pathophysiological
      information about the urethra to what can be obtained on the basis of
      conventional urodynamic work-up. Further studies are needed to prove if this new
      method is useful for clinical and research purposes.

PMID- 17016845
TI  - TURP and low-energy TUMT treatment in men with LUTS suggestive of bladder outlet
      obstruction selected by means of pressure-flow studies: 8-year follow-up.
AB  - AIMS: To evaluate the long-term outcome of transurethral resection of the
      prostate (TURP) and transurethral microwave thermotherapy (TUMT) in men with
      symptomatic benign prostatic hyperplasia (BPH), when allocation to the treatment
      group was based on urodynamic diagnosis of bladder outlet obstruction (BOO).
      METHODS: A total of 231 elderly men with symptomatic BPH were treated either by
      TURP or by low-energy TUMT. A pressure-flow study was performed to detect the
      obstruction and to help in the selection of the two treatments. The patients were
      examined at baseline then checked again after 2 and 8 years. RESULTS: At 2 years
      of follow-up there was a significant improvement for both IPSS and QoL (P <
      0.0001) in both groups of treatment. This was accompanied by a significant
      improvement (P < 0.0001) in the maximum flow rate from 10.0 (5.8) to 16.4 (7.6)
      in the TURP group and from 12.1 (5.2) to 14.9 (5.7) in the TUMT group. These
      findings persisted at 8 years, they were, however, more pronounced after TURP.
      The overall retreatment rate reached a value of 11% in the TURP group and 27% in
      the TUMT group, respectively. At the follow-up, 95% of the patients who underwent
      TURP and 70% of the patients treated by TUMT claimed to be satisfied with that
      choice. CONCLUSIONS: With durable symptomatic improvement and lowest retreatment
      rate, TURP still presents a standard treatment option for patients with severe
      BOO. Low-energy TUMT has sufficiently relieved patients' symptoms and can be
      offered to less obstructed patients as an alternative.

PMID- 17016846
TI  - Latrophilin-2 is a novel component of the epithelial-mesenchymal transition
      within the atrioventricular canal of the embryonic chicken heart.
AB  - Endothelial cells in the atrioventricular canal of the heart undergo an
      epithelial-mesenchymal transition (EMT) to form heart valves. We surveyed an on
      line database (http://www.geisha.arizona.edu/) for clones expressed during
      gastrulation to identify novel EMT components. One gene, latrophilin-2, was
      identified as expressed in the heart and appeared to be functional in EMT. This
      molecule was chosen for further examination. In situ localization showed it to be
      expressed in both the myocardium and endothelium. Several antisense DNA probes
      and an siRNA for latrophilin-2 produced a loss of EMT in collagen gel cultures.
      Latrophilin-2 is a putative G-protein-coupled receptor and we previously
      identified a pertussis toxin-sensitive G-protein signal transduction pathway.
      Microarray experiments were performed to examine whether these molecules were
      related. After treatment with antisense DNA against latrophilin-2, expression of
      1,385 genes and ESTs was altered. This represented approximately 12.5% of the
      microarray elements. In contrast, pertussis toxin altered only 103 (0.9%)
      elements of the array. There appears to be little overlap between the two signal
      transduction pathways. Latrophilin-2 is thus a novel component of EMT and
      provides a new avenue for investigation of this cellular process.

PMID- 17016842
TI  - The International Society for Developmental Psychobiology annual meeting
      symposium: Impact of early life experiences on brain and behavioral development.
AB  - Decades of research in the area of developmental psychobiology have shown that
      early life experience alters behavioral and brain development, which canalizes
      development to suit different environments. Recent methodological advances have
      begun to identify the mechanisms by which early life experiences cause these
      diverse adult outcomes. Here we present four different research programs that
      demonstrate the intricacies of early environmental influences on behavioral and
      brain development in both pathological and normal development. First, an animal
      model of schizophrenia is presented that suggests prenatal immune stimulation
      influences the postpubertal emergence of psychosis-related behavior in mice.
      Second, we describe a research program on infant rats that demonstrates how early
      odor learning has unique characteristics due to the unique functioning of the
      infant limbic system. Third, we present work on the rodent Octodon degus, which
      shows that early paternal and/or maternal deprivation alters development of
      limbic system synaptic density that corresponds to heightened emotionality.
      Fourth, a juvenile model of stress is presented that suggests this developmental
      period is important in determining adulthood emotional well being. The approach
      of each research program is strikingly different, yet all succeed in delineating
      a specific aspect of early development and its effects on infant and adult
      outcome that expands our understanding of the developmental impact of infant
      experiences on emotional and limbic system development. Together, these research
      programs suggest that the developing organism's developmental trajectory is
      influenced by environmental factors beginning in the fetus and extending through
      adolescence, although the specific timing and nature of the environmental
      influence has unique impact on adult mental health.

PMID- 17016847
TI  - Shh/BMP-4 signaling pathway is essential for intestinal epithelial development
      during Xenopus larval-to-adult remodeling.
AB  - During amphibian larval-to-adult intestinal remodeling, progenitor cells of the
      adult epithelium actively proliferate and differentiate under the control of
      thyroid hormone (TH) to form the intestinal absorptive epithelium, which is
      analogous to the mammalian counterpart. We previously found that TH-up-regulated
      expression of bone morphogenetic protein-4 (BMP-4) spatiotemporally correlates
      with adult epithelial development in the Xenopus laevis intestine. Here, we aimed
      to clarify the role of BMP-4 in intestinal remodeling. Our reverse transcriptase
      polymerase chain reaction and in situ hybridization analyses indicated that mRNA
      of BMPR-IA, a type I receptor of BMP-4, is expressed in both the developing
      connective tissue and progenitor cells of the adult epithelium. More importantly,
      using organ culture and immunohistochemical procedures, we have shown that BMP-4
      not only represses cell proliferation of the connective tissue but promotes
      differentiation of the intestinal absorptive epithelium. In addition, we found
      that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by
      sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by
      TH. These results strongly suggest that the Shh/BMP-4 signaling pathway plays key
      roles in the amphibian intestinal remodeling through epithelial-connective tissue
      interactions.

PMID- 17016848
TI  - Effects of hypomagnetic field on noradrenergic activities in the brainstem of
      golden hamster.
AB  - Previous studies found that elimination of the geomagnetic field (GMF) interferes
      with the normal brain functions, but the underlying mechanism remains unknown.
      The present study examined the effects of long-term exposures to a near-zero
      magnetic environment on the noradrenergic activities in the brainstem of golden
      hamsters. Both the content of norepinephrine (NE) and the density of NE
      immunopositive neurons in the tissue decreased significantly after the treatment,
      and the effects could be progressive with time. These variations may
      substantially contribute to behavioral and mood disorders reported in other
      studies when animals are shielded from the GMF.

PMID- 17016850
TI  - Thirty-five years in bioelectromagnetics research.
AB  - For 35 years, I have been involved in various bioelectromagnetics research
      projects including acute and long-term radiofrequency (RF) bioeffects studies,
      dosimetry, exposure systems, MRI safety, cancer studies involving hyperthermia
      and electrochemical treatment, development of RF exposure and measurement
      standards, and product compliance. My first study demonstrated that effects on
      isolated nerve and muscle preparations were due to thermal effects of RF
      exposure. The recording of cochlear microphonics in animals shows the mechanical
      nature of the microwave auditory effect. In 1992, we published the results of a
      large-scale lifetime study in which 100 rats were sham-exposed and 100 rats were
      exposed for 21 h/day for 25 months to a pulsed RF signal. In dosimetry studies,
      human models were employed as well as many animal species including mice, rats,
      rabbits, monkeys, and birds of many sizes. Cancer hyperthermia studies
      demonstrated that knowledge of temperature distribution was crucial for
      successful treatment. Research on electrochemical treatment of tumors with direct
      current involved cellular, animal, and clinical studies. Over the past few
      decades, there has been rather extensive investigation of the public health
      impact of RF exposure. In my opinion, future research in bioelectromagnetics
      should place greater emphasis on medical applications.

PMID- 17016851
TI  - Unexpected inhibitory regulation of glutamate release from rat cerebrocortical
      nerve terminals by presynaptic 5-hydroxytryptamine-2A receptors.
AB  - Presynaptic 5-HT(2A) receptor modulation of glutamate release from rat
      cerebrocortical nerve terminals (synaptosomes) was investigated by using the 5
      HT(2A/2C) receptor agonist (+/-)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane
      (DOI). DOI potently inhibited 4-aminopyridine (4AP)-evoked glutamate release.
      Involvement of presynaptic 5-HT(2A) receptors in this modulation of 4AP-evoked
      release was confirmed by blockade of the DOI-mediated inhibition by the 5-HT(2A)
      receptor antagonist ketanserin but not by the 5-HT(2C) receptor antagonist
      RS102221. Inhibition of glutamate release by DOI was associated with a reduction
      of 4AP-evoked depolarization and downstream elevation of cytoplasmic free calcium
      concentration ([Ca(2+)](C)) mediated via P/Q- and N-type voltage-dependent Ca(2+)
      channels (VDCCs). In contrast to the DOI effect on 4AP-evoked release, the
      agonist had no effect on high external [K(+)] (30 mM)-induced (KCl) stimulation
      of VDCCs or glutamate release. Likewise, release mediated by direct Ca(2+) entry
      with Ca(2+) ionophore (ionomycin) or by hypertonic sucrose was unaffected by DOI.
      Mechanistically, DOI modulation of 4AP-evoked glutamate release appeared to
      involve a phospholipase C/protein kinase C signaling cascade, insofar as
      pretreatment of synaptosomes with the phospholipase C inhibitor U73122 or protein
      kinase C inhibitors Ro320432 or GF109203X all effectively occluded the inhibitory
      effect of the agonist. Together, these results suggest that presynaptic 5-HT(2A)
      receptors present on glutamatergic terminals effect an unexpected depression of
      glutamate release by negatively modulating nerve terminal excitability and
      downstream VDCC activation through a signaling cascade involving phospholipase
      C/protein kinase C. These observations invoke presynaptic inhibitory 5-HT(2A)
      receptor function as a potential target for drugs to mitigate the effects of
      excessive glutamatergic transmission.

PMID- 17016852
TI  - Astrocytes refill intracellular Ca2+ stores in the absence of cytoplasmic [Ca2+]
      elevation: a functional rather than a structural ability.
AB  - Capacitative Ca(2+) entry (CCE) is a phenomenon triggered by depletion of Ca(2+)
      content in intracellular stores (ICS). Data about this phenomenon in astrocytes
      are limited. We analyzed CCE in astrocytes by means of fura-2 based digital
      imaging. We found that in astrocytes CCE is not associated with an increase of
      cytosolic Ca(2+) concentration ([Ca(2+)](i)), although ICS are efficiently
      refilled. We used Mn(2+), thapsigargin and prolonged ATP exposure to show that
      CCE is not associated with cytosolic diffusion of Ca(2+) entering astrocytes. Our
      data suggest that the ion is being quickly sequestered in the ICS by the smooth
      endoplasmic reticulum Ca(2+)-ATP-ase (SERCA). Several experiments were carried
      out with the goal of failing the efficient uptake in the endoplasmic reticulum
      (ER). In fact, inhibition of SERCA activity, increased extracellular [Ca(2+)](i)
      or pharmacologic potentiation of CCE all caused [Ca(2+)](i) elevation during CCE,
      suggesting that the control of this phenomenon could have physiologic and
      pathological relevance. The molecular components involved in CCE have been
      proposed to be organized in a multi-molecular complex tethered by cytoskeleton
      components and arranged via a secretion coupling model. We show here that the
      efficient routing of Ca(2+) into the ICS in astrocytes is not affected by
      disruption of cytoskeleton organization or Golgi's function, but it is instead
      linked to the high efficiency of SERCA. We conclude that depleted ICS in
      astrocytes are efficiently refilled by CCE activation, although Ca(2+) influx is
      not accompanied by elevation of [Ca(2+)](i). This ability seems to be functional
      rather than structural in nature.

PMID- 17016853
TI  - The pharmacodynamic effects of sirolimus and sirolimus-calcineurin inhibitor
      combinations on macrophage scavenger and nuclear hormone receptors.
AB  - BACKGROUND: Sirolimus (SIR) alone or in combination with cyclosporine (CsA) or
      tacrolimus (TAC) are used in solid organ transplantation, but uncertainty remains
      regarding their respective atherogenic potentials. METHODS: THP-1 cells were
      cultured as macrophages and then treated with plasma trough and peak
      concentration doses of SIR, SIR/CsA or SIR/TAC to assess the time- and dose
      dependent mRNA or protein expression of selected atherogenic genes. The selected
      atherogenic genes included: the macrophage scavenger receptors (MSRs) CD36, CD68,
      scavenger receptor (SR)-A, SR-BII, and LOX-1; the nuclear hormone receptors
      peroxisome proliferator activated receptor gamma (PPARgamma) and liver-X-receptor
      alpha (LXRalpha); and the cholesterol efflux transporter (ABCA-1). RESULTS: SIR
      mediated changes in mRNA included the upregulation of ABCA1, downregulation of
      CD68, SR-A and SR-BII, and concentration- and/or time-dependent effects on CD36,
      LOX-1, PPARgamma, and LXRalpha that did not translate into significant protein
      changes. With SIR/CsA, the protein expressions of PPARgamma and ABCA-1 were
      downregulated at 8 h. In contrast, with SIR/TAC, PPARgamma, and ABCA-1 protein
      expressions were upregulated at 8 h. CONCLUSIONS: Combination results differed
      from findings with SIR alone, supporting the observed clinical phenotype with
      calcineurin inhibitors. These findings may provide a rationale for the
      development of novel drug delivery strategies to mitigate adverse pharmacodynamic
      responses.

PMID- 17016854
TI  - Activation of adenosine A3 receptors reduces ischemic brain injury in rodents.
AB  - Adenosine A3 receptor (A3R) agonists have been shown to reduce cardiac and lung
      injury, but the protective roles of A3R agonists in the CNS are not well
      characterized. The protective effect of selective A3R agonist chloro-N(6)-(3-iodo
      benzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA) was first examined in primary
      cortical cultures. In cortical culture, Cl-IB-MECA pretreatment antagonized the
      hypoxia-mediated decrease in cell viability. In vivo, Cl-IB-MECA or vehicle was
      given intracerebroventricularly or intravenously to anesthetized rats. Animals
      were subjected to focal cerebral ischemia induced by transient middle cerebral
      artery (MCA) ligation. Intracerebroventricular or repeated intravenous
      administration (i.e., at 165 min and 15 min before MCA ligation) of Cl-IB-MECA
      did not alter blood pressure during ischemia but increased locomotor activity and
      decreased cerebral infarction 2 days after. In these animals, Cl-IB-MECA also
      reduced the density of TUNEL labeling in the lesioned cortex. The possibility of
      endogeneous neuroprotection was further examined in A3R knockout mice. After MCA
      ligation, an increase in cerebral infarction was found in the A3R knockouts
      compared with the A3R wild-type controls, suggesting that A3Rs are tonically
      activated during ischemia. Additionally, intracerebroventricular pretreatment
      with Cl-IB-MECA decreased the size of infarction in the wild-type controls, but
      not in the A3R knockout animals, suggesting that Cl-IB-MECA-induced protection
      was mediated through the A3 receptors. Collectively, these data suggest that Cl
      IB-MECA reduced cerebral infarction through the activation of A3Rs and
      suppression of apoptosis.

PMID- 17016855
TI  - Inhibition of integrin alphavbeta3 reduces blood-brain barrier breakdown in focal
      ischemia in rats.
AB  - Ischemic stroke is a major cause of morbidity and mortality in industrialized
      nations. We tested the effect of postischemic treatment of cyclo-RGDfV (cRGDfV),
      a selective inhibitor of integrin alphavbeta3, in the middle cerebral artery
      occlusion (MCAO) model of ischemic stroke in rats. Rats were randomly divided
      into three groups: sham operation (n = 13), MCAO with no treatment (n = 18), and
      MCAO with cRGDfV treatment (n = 28). Focal ischemia was induced with the suture
      occlusion method for 2 hr, and treatment was given 1 hr after reperfusion (3 hr
      after ischemia). All animals were sacrificed 24 hr after reperfusion. Assessment
      included neurological scores, infarction volumes, brain water content, Evans blue
      exudation, IgG exudation, histology, immunohistochemistry, and Western blotting.
      Treatment with cRGDfV ameliorated neurological deficits, reduced brain edema, and
      reduced exudation of Evans blue dye and IgG, but failed to reduce infarction
      volumes. Western blotting showed a reduction in phosphorylation of one subset of
      vascular endothelial growth factor (VEGF) receptors in the cRGDfV treatment
      group. Western blotting also demonstrated a significant reduction of fibrinogen
      in the cRGDfV treatment group. We conclude that poststroke treatment with cRGDfV
      reduces blood-brain barrier breakdown in focal ischemia, possibly through
      inhibition of VEGF-mediated vascular breakdown.

PMID- 17016857
TI  - Polycystin-1 can interact with homer 1/Vesl-1 in postnatal hippocampal neurons.
AB  - Polycystin-1 (PC-1) has been identified as critical to development of the nervous
      system, but the significance of PC-1 expression in neurons remains undefined, and
      little is known of its roles outside the kidney, where mutation results in
      autosomal dominant polycystic kidney disease (ADPKD). In kidney, PC-1 interacts
      with cadherins, catenins, and its cognate calcium channel polycystin-2 (PC-2),
      which in turn interacts with a number of actin-regulatory proteins. Because some
      of the proteins that interact with PC-1 in kidney also participate in synaptic
      remodeling and plasticity in the hippocampus, we decided to test PC-1's potential
      to interact with a recently discovered type of plasticity-associated protein
      (homer 1a/Vesl-1S) in postnatal mouse hippocampus. Homer 1a/Vesl-1S is an
      activity-induced protein believed to participate in synaptic
      remodeling/plasticity responses to temporal lobe seizure and learning. Here we
      report the following. 1) PC-1 contains a homer-binding motif (PPxxF), which lies
      within its purported cytoplasmic domain. 2) Immunoreactivity for PC-1 (PC-1-ir)
      is highly colocalized with homer 1a immunoreactivity (H1a-ir) in primary cultured
      hippocampal neurons. 3) PC-1-ir and H1a-ir are present and appear to be
      colocalized in mouse hippocampus but not cortex on postnatal day 2 (P2), when
      higher frequencies of spontaneous activity are normal for hippocampus compared
      with cortex. 4) An endogenous PC-1-ir band with the correct size for the reported
      C-terminal G-protein-sensitive domain cleavage product of PC-1 (approximately 150
      kDa) coimmunoprecipitates with endogenous homer 1/Vesl-1 proteins from mouse
      brain, suggesting that PC-1 can interact with homer 1/Vesl-1 proteins in
      postnatal hippocampal neurons.

PMID- 17016858
TI  - Early postnatal chronic inflammation produces long-term changes in pain behavior
      and N-methyl-D-aspartate receptor subtype gene expression in the central nervous
      system of adult mice.
AB  - The objective of this study was to test whether postnatal chronic inflammation
      resulted in altered reactivity to pain later in life when reexposed to the same
      inflammatory agent and whether this alteration correlated with brain-region
      specific patterns of N-methyl-D-aspartate (NMDA) receptor subtype gene
      expression. Neonatal mouse pups received a single injection of complete Freund's
      adjuvant (CFA) or saline into the left hind paw on postnatal day 1 or 14. At 12
      weeks of age, both neonatal CFA- and saline-treated animals received a unilateral
      injection of CFA in the left hind paw. Adult behavioral responsiveness of the
      left paw to a radiant heat source was determined in mice treated neonatally with
      saline or CFA before and after receiving CFA as adults. Twenty-four hours later,
      brains were dissected and NMDA receptor subunit gene expression was determined in
      four different brain areas by using an RNase protection assay. The results
      indicated that NMDA receptor subtype gene expression in adult mice exposed to
      persistent neonatal peripheral inflammation was brain region specific and that
      NMDA gene expression and pain reactivity differed according to the day of
      neonatal CFA exposure. Similarly, adult behavioral responsiveness to a noxious
      radiant heat source differed according to the age of neonatal exposure to CFA.
      The data suggest a possible molecular basis for the hypothesis that chronic
      persistent inflammation experienced early during development may permanently
      alter the future behavior and the sensitivity to pain later in life, especially
      in response to subsequent or recurrent inflammatory events.

PMID- 17016859
TI  - Integrin alpha3beta1 interacts with I1PP2A/lanp and phosphatase PP1.
AB  - Integrin alpha3beta1 is a receptor for the extracellular matrix component laminin
      5. To elucidate possible signaling pathways induced by integrin alpha3beta1, we
      looked for proteins that interact with the cytoplasmic part of the alpha3A
      integrin subunit. We identified several multifunctional proteins by affinity
      chromatography and subsequent MALDI-TOF-MS and focused on the inhibitor 1 of
      serine/threonine phosphatase PP2A (I1PP2A, synonym: lanp) which also plays a role
      during the development of the mouse cerebellum. I1PP2A/lanp colocalizes with the
      alpha3A integrin subunit in differentiated PC12 cells in the cell body and in
      neurites as well as in Purkinje cells of mouse cerebellum. Overexpression of GFP
      I1PP2A/lanp in PC12 cells leads to markedly reduced neurite length on laminin 5
      after induction with nerve growth factor. By affinity chromatography the protein
      phosphatase PP1 can also be identified as a alpha3A/cyto-binding protein. PP1 and
      integrin alpha3beta1 can be pulled down by GST-I1PP2A/lanp from cell lysates of
      differentiated and undifferentiated PC12 cells. The phosphatase binds to the
      cytoplasmic membrane-proximal conserved GFFKR motif of the alpha integrin
      subunit, whereas I1PP2A/lanp requires a longer sequence for binding. PP1 but not
      PP2A is able to dephosphorylate precipitated integrin alpha3beta1 in vitro.
      Furthermore, PP1 releases phosphate from T1046 of phosphopeptides that mimic the
      phosphorylation consensus sequence in the cytoplasmic part of the alpha3A
      integrin subunit. These data suggest that I1PP2A/lanp forms a complex with PP1
      and the alpha3A integrin subunit and might possibly regulate the phosphorylation
      status of integrin alpha3beta1 and/or integrin downstream targets.

PMID- 17016860
TI  - A generic stepwise optimization strategy for liquid chromatography electrospray
      ionization tandem mass spectrometry methods.
AB  - The feasibility and advantages of using sophisticated chemometric tools in
      combination with the execution of thoroughly planned experiments to determine
      experimental conditions for optimal performance of an LC-ESI-MS/MS analysis is
      demonstrated. A stepwise strategy is proposed, which provides a controlled
      optimization procedure of the chromatographic quality (in terms of separation
      among the sample constituents) and maximizes the mass spectrometric signal of the
      selected product ions. Design of experiments (DOE) and response surface
      methodology are applied throughout the procedure. The stepwise approach has the
      advantage of dealing with the different optimization criteria separately, i.e.
      first ensuring sufficient chromatographic separation, then maximizing the amount
      of precursor ion entering the mass spectrometer, and finally generating high
      amounts of selected product ions. The experiments are performed on a linear ion
      trap mass spectrometer. Retention mapping using the band-tracking model is
      applied during LC development, which facilitates the optimization of segmented
      gradients. A set of different siderophores, strong iron chelates, is used as the
      model substances.

PMID- 17016861
TI  - Tandem mass spectra of divalent metal ion adducts of glycosyl sulfides,
      sulfoxides and sulfones; distinction among stereoisomers.
AB  - The tandem mass spectra of the divalent metal ion (Mg2+, Ca2+, Sr2+, Ba2+, Mn2+,
      Ni2+, Co2+ and Zn2+) adducts of acetylated 1,2-trans-glycosyl sulfides,
      sulfoxides and sulfones were examined using low energy collision-induced
      dissociation on a Quattro II quadrupole tandem mass spectrometer. Abundant doubly
      charged ions, such as [3M + Met]2+ and [2M + Met]2+, were observed with alkaline
      earth metal chlorides. The other ions observed were [M + MetCl]+, [M + MetOAc]+,
      [M + MetO2SPh]+ and [2M + MetCl]+. The deprotonated metal adducts [M + Met-H]+
      were seen only in the sulfones. The divalent metal ion adducts showed
      characteristic fragmentation pathways for the glycosyl sulfides, sulfoxides and
      sulfones, depending on the site of metal attachment. The doubly charged metal ion
      adducts dissociate to two singly charged ions, [M + MetOAc]+ and [M - OAc]+, in
      the sulfides and sulfoxides. In the sulfones, the adducts dissociate to [M +
      MetO2SPh]+ and [M - O2SPh]+. In contrast to the alkaline earth metals, which
      attach to the acetoxy functions, the transition metals attach to the sulfide and
      sulfoxide functions. The metal chloride adducts display characteristic
      fragmentation for the sulfides, sulfoxides and sulfones. The glucosyl, mannosyl
      and galactosyl sulfides, sulfoxides and sulfones could be differentiated on the
      basis of the stereochemically controlled MS/MS fragmentations of the metal
      chloride adducts.

PMID- 17016862
TI  - Estimation of the proportion of overweight individuals in small areas - a robust
      extension of the Fay-Herriot model.
AB  - Hierarchical model such as Fay-Herriot (FH) model is often used in small area
      estimation. The method might perform well overall but is vulnerable to outliers.
      We propose a robust extension of the FH model by assuming the area random effects
      follow a t distribution with an unknown degrees-of-freedom parameter. The
      inferences are constructed using a Bayesian framework. Monte Carlo Markov Chain
      (MCMC) such as Gibbs sampling and Metropolis-Hastings acceptance and rejection
      algorithms are used to obtain the joint posterior distribution of model
      parameters. The procedure is used to estimate the county-level proportion of
      overweight individuals from the 2003 public-use Behavioral Risk Factor
      Surveillance System (BRFSS) data. We also discuss two approaches for identifying
      outliers in the context of this application.

PMID- 17016863
TI  - Bayesian analysis of structural equation models with multinomial variables and an
      application to type 2 diabetic nephropathy.
AB  - There is now increasing evidence proving that many complex diseases can be
      significantly influenced by correlated phenotype and genotype variables, as well
      as their interactions. Effective and rigorous assessment of such influence is
      difficult, because the number of phenotype and genotype variables of interest may
      not be small, and a genotype variable is an unordered categorical variable that
      follows a multinomial distribution. To address the problem, we establish a novel
      nonlinear structural equation model for analysing mixed continuous and
      multinomial data that can be missing at random. A confirmatory factor analysis
      model with Kronecker product is proposed for grouping the manifest continuous and
      multinomial variables into latent variables according to their functions; and a
      nonlinear structural equation is formulated to assess the linear and interaction
      effects of the independent latent variables to the dependent latent variables.
      Bayesian methods for estimation and model comparison are developed through Markov
      chain Monte Carlo techniques and path sampling. The newly developed methodologies
      are applied to a case-control cohort of type 2 diabetic patients with
      nephropathy.

PMID- 17016864
TI  - Properties of analysis methods that account for clustering in volume-outcome
      studies when the primary predictor is cluster size.
AB  - In recent years health services researchers have conducted 'volume-outcome'
      studies to evaluate whether providers (hospitals or surgeons) who treat many
      patients for a specialized condition have better outcomes than those that treat
      few patients. These studies and the inherent clustering of events by provider
      present an unusual statistical problem. The volume-outcome setting is unique in
      that 'volume' reflects both the primary factor under study and also the cluster
      size. Consequently, the assumptions inherent in the use of available methods that
      correct for clustering might be violated in this setting. To address this issue,
      we investigate via simulation the properties of three estimation procedures for
      the analysis of cluster correlated data, specifically in the context of volume
      outcome studies. We examine and compare the validity and efficiency of widely
      available statistical techniques that have been used in the context of volume
      outcome studies: generalized estimating equations (GEE) using both the
      independence and exchangeable correlation structures; random effects models; and
      the weighted GEE approach proposed by Williamson et al. (Biometrics 2003; 59:36
      42) to account for informative clustering. Using data generated either from an
      underlying true random effects model or a cluster correlated model we show that
      both the random effects and the GEE with an exchangeable correlation structure
      have generally good properties, with relatively low bias for estimating the
      volume parameter and its variance. By contrast, the cluster weighted GEE method
      is inefficient.

PMID- 17016865
TI  - Re: fetal magnetic resonance imaging: luxury or necessity?

PMID- 17016866
TI  - Effect of thermal processing on the flavonols rutin and quercetin.
AB  - The current research involves the study of the thermal treatment of quercetin and
      rutin in an aqueous model system (cooking). These substances were heated and
      their degradation was followed by high-performance liquid chromatography/diode
      array detection (HPLC/DAD). The influence of pH and the involvement of oxygen in
      the degradation were studied. HPLC/electrospray ionization multi-stage mass
      spectrometry (ESI-MS(n)) was used for the structural characterization of the
      compounds produced. The influence of the degradation of the phenolic compounds on
      their antioxidant properties was elucidated by a electron spin resonance (ESR)
      spectrometry study of the reaction samples mixed with the stabilized radical,
      Fremy's salt. Strong degradation of the model substances took place under weak
      basic and oxidative conditions. Quercetin showed the most intense degradation.
      Protocatechuic acid could be identified as a cleavage reaction product by
      analyzing its retention time and molar mass during the degradation of quercetin.
      The structure of a second cleavage product could be identified on the basis of
      ESI-MS(n) fragmentation data. Also, several structures for reaction products of
      oxidized quercetin are suggested. The ESR analysis showed a decrease in the
      antioxidant activity of the reaction samples after heat treatment in aqueous
      solution.

PMID- 17016867
TI  - An adaptive phase I design for identifying a biologically optimal dose for dual
      agent drug combinations.
AB  - Historically, designs for dose seeking trials using chemotherapeutic drug
      combinations have been geared towards finding the maximum tolerated dose, with
      safety as the primary outcome. With target based agents whose dose-efficacy
      curves are unknown and dose-toxicity relationships may be minimal, alternative
      designs are needed. In this paper, we propose an extension to an adaptive single
      agent dose-finding design previously reported. A generalization of the
      continuation ratio model allowing separate toxicity and efficacy curves for each
      agent in a dual agent combination, generating a dose success surface for the
      combination, is proposed. A continual reassessment approach with a
      straightforward dose selection criterion using the accumulated data from all
      patients treated to that point is employed. Our simulation studies demonstrate
      favourable operating characteristics in terms of experimentation and
      recommendation rates, and the average sample size, under a variety of scenarios.
      The proposed approach allowing the incorporation of both the toxicity and
      efficacy of each agent into the identification of an optimal dosing region for a
      combination is novel and warrants further consideration.

PMID- 17016868
TI  - Combined use of Overhauser spectroscopy and NMR diffusion experiments for mapping
      the hydration structure of nucleosides: structure and dynamics of uridine in
      water.
AB  - Complementary results from 13C intermolecular nuclear Overhauser effects (NOE),
      1H-13C heteronuclear Overhauser spectroscopy (HOSEY) and 1H-NMR diffusion
      measurements were used for probing the structure of the first solvation shell of
      uridine in water. It is demonstrated that a cyclic dihydrate is formed. The two
      water molecules produce two hydrogen bonds with the two oxygen atoms from the
      pyrimidine ring and accept only one hydrogen bond from the amide proton. The
      dihydrate has only a short lifetime as compared with the rotational correlation
      time of the free nucleoside. The chemical exchange constant of the amide proton
      with water is then estimated by diffusion experiments. The results are consistent
      with previous data obtained for uracil in water and provide interesting
      information about water accessibility in nucleic acid bases.

PMID- 17016869
TI  - Take me out to the hospital.

PMID- 17016870
TI  - Prevalence of incidentally discovered thyroid nodules on computed tomographic
      scanning and magnetic resonance imaging.

PMID- 17016871
TI  - Piping hot.

PMID- 17016872
TI  - Sticking in there.

PMID- 17016873
TI  - Q & A. Nicholas Wade.

PMID- 17016874
TI  - US advisory panel revisits prison research rules.

PMID- 17016876
TI  - Current awareness on yeast.

PMID- 17016877
TI  - Occurrence of goitre during lithium treatment.
AB  - Of 330 patients given lithium for recurrent manic-depressive disorder 12
      developed goitre after treatment periods of five months to two years. All the
      patients remained clinically euthyroid. Pressure symptoms necessitated subtotal
      thyroidectomy in two patients. In 9 out of 10 patients with goitre, and in two
      out of seven without goitre study with radioactive iodine showed abnormal
      findings in iodine metabolism. Discontinuance of lithium led to disappearance of
      goitres, while thyroid metabolism returned to normal. Thyroxine or desiccated
      thyroid produced shrinkage of the gland in spite of continued lithium medication.

PMID- 17016878
TI  - Treatment for adult HIV infection: 2006 recommendations of the International AIDS
      Society--USA panel.
AB  - CONTEXT: Guidelines for antiretroviral therapy are important for clinicians
      worldwide given the complexity of the field and the varied clinical situations in
      which these agents are used. The International AIDS Society-USA panel has updated
      its recommendations as warranted by new developments in the field. OBJECTIVE: To
      provide physicians and other human immunodeficiency virus (HIV) clinicians with
      current recommendations for the use of antiretroviral therapy in HIV-infected
      adults in circumstances for which there is relatively unrestricted access to
      drugs and monitoring tools. The recommendations are centered on 4 key issues:
      when to start antiretroviral therapy; what to start; when to change; and what to
      change. Antiretroviral therapy in special circumstances is also described. DATA
      SOURCES AND STUDY SELECTION: A 16-member noncompensated panel was appointed,
      based on expertise in HIV research and patient care internationally. Data
      published or presented at selected scientific conferences from mid 2004 through
      May 2006 were identified and reviewed by all members of the panel. DATA
      EXTRACTION AND SYNTHESIS: Data that might change previous guidelines were
      identified and reviewed. New guidelines were drafted by a writing committee and
      reviewed by the entire panel. CONCLUSIONS: Antiretroviral therapy in adults
      continues to evolve rapidly, making delivery of state-of-the-art care
      challenging. Initiation of therapy continues to be recommended in all symptomatic
      persons and in asymptomatic persons after the CD4 cell count falls below
      350/microL and before it declines to 200/microL. A nonnucleoside reverse
      transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir
      each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors
      is recommended with choice being based on the individual patient profile. Therapy
      should be changed when toxicity or intolerance mandate it or when treatment
      failure is documented. The virologic target for patients with treatment failure
      is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral
      therapy in the short-term and the long-term is crucial for treatment success and
      must be continually reinforced.

PMID- 17016879
TI  - Managing alcohol problems, part 1.
AB  - Alcohol is the most widely used and abused drug in the United States. Each year,
      17 million adults experience a serious problem with alcohol, but only 3 million
      get help. Risky or problem drinking can jeopardize the health and safety of not
      only those who drink but also their families, coworkers, and communities. Because
      of their collaborative approach to helping clients achieve wellness and
      independence, case managers are in a prime position to identify and address
      clients' alcohol problems.

PMID- 17016880
TI  - The role of feelings in making moral decisions.

PMID- 17016881
TI  - Mental health and court decisions.

PMID- 17016882
TI  - Scheduling is not for the faint of heart.

PMID- 17016883
TI  - Cardiovascular health human resources.

PMID- 17016884
TI  - Too many patients, too few cardiologists to care?

PMID- 17016885
TI  - Burning mouth syndrome: an update on recent findings.
AB  - Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral
      mucosa in the absence of mucosal abnormality. Various local, systemic and
      psychological factors are associated with BMS, but its aetiology is not fully
      understood. Recently, significant inroads have been made, producing a better
      understanding of this complex condition. The aim of the current paper is to
      explore the condition of BMS in an educational context with the specific outcome
      of increasing awareness of the condition.

PMID- 17016886
TI  - Fund allocation within Australian dental care: an innovative approach to output
      based funding.
AB  - BACKGROUND: Over the last 15 years in Australia the process of funding government
      health care has changed significantly. The development of dental funding models
      that transparently meet both the service delivery needs for data at the treatment
      level and policy makers' need for health condition data is critical to the
      continued integration of dentistry into the wider health system. METHODS: This
      paper presents a model of fund allocation that provides a communication construct
      that addresses the needs of both policy makers and service providers. RESULTS: In
      this model, dental treatments (dental item numbers) have been grouped into eight
      broad dental health conditions. Within each dental health condition, a weighted
      average price is determined using the Department of Veterans Affairs' (DVA) fee
      schedule as the benchmark, adjusted for the mix of care. The model also adjusts
      for the efficiency differences between sectors providing government funded dental
      care. In summary, the price to be applied to a dental health condition category
      is determined by the weighted average DVA price adjusted by the sector
      efficiency. CONCLUSIONS: This model allows governments and dental service
      providers to develop funding agreements that both quantify and justify the
      treatment to be provided. Such a process facilitates the continued integration of
      dental care into the wider health system.

PMID- 17016887
TI  - The potential for dental plaque to protect against erosion using an in vivo-in
      vitro model--a pilot study.
AB  - BACKGROUND: Tooth erosion is a problem for professional wine tasters (exogenous
      erosion from frequent exposure to wine acids) and for people with gastro
      oesophageal reflux disease (GORD) and bulimia who experience frequent reflux of
      gastric contents into the mouth (endogenous erosion from mainly HCl). The
      objective in this study was to determine whether plaque/pellicle could provide
      teeth with any protection from two common erosive acids, using an in vivo-in
      vitro technique. METHODS: Tiles of human tooth enamel and root surfaces were
      prepared from six extracted, unerupted third molar teeth and sterilized.
      Mandibular stents were prepared for six volunteer subjects and the tiles bonded
      to the buccal flanges of these stents. They were worn initially for three days to
      permit a layer of pellicle and plaque to form over the tile surfaces, and for a
      further 10 days of experimentation. Following cleaning of the plaque/ pellicle
      layer from the tiles on the right side flange, all the tiles were submerged in
      either 0.06M HCl or white wine for an accumulated time of 600 and 1500 minutes,
      respectively. Depths of erosion were determined using light microscopy of
      sections of the enamel and root tiles. SEM of the lesion surfaces was carried out
      to investigate the nature of erosive damage and of plaque/pellicle remnants.
      RESULTS: Retained plaque was found to significantly inhibit dental erosion on
      enamel, from contact with both HCl and wine, compared with that resulting
      following its removal. However, it was found to provide no significant protection
      on root surfaces. SEM analysis of the tile surfaces revealed marked etching of
      enamel on the cleaned surfaces, and considerable alteration to the appearance of
      remaining plaque and pellicle on most surfaces. CONCLUSION: Within the
      limitations of numbers of specimens, dental plaque/pellicle provided a
      significant level of protection to tooth enamel against dental erosion from
      simulated gastric acids and from white wine, using an in vivo-in vitro model. It
      was unable to provide any significant protection to root surfaces from these
      erosive agents. Possible reasons for this difference are explored.

PMID- 17016888
TI  - Dentist-patient communication in the multilingual dental setting.
AB  - BACKGROUND: Communication between dentists and patients can be exceptionally
      challenging when the patient and the dentist do not speak the same language, as
      is frequently the case in multicultural Australia. The aim of this study was to
      describe the issues involved in dealing with limited-English speaking patients in
      order to formulate recommendations on how to improve dental communication.
      METHODS: A cross sectional study was performed using a postal survey to
      Australian Dental Association member dental practitioners in Western Australia.
      Responses were collated and data analysis was performed using SPSS 11.5 for
      Windows. RESULTS: Most respondents encounter language-related communication
      barriers weekly or monthly, and the most satisfactory method of communication is
      informal interpreters. Despite reporting satisfaction working with professional
      chairside interpreters or dental staff interpreters, most respondents did not use
      them. The most common alternative communication methods were diagrams and models.
      Endodontics and periodontics provided the greatest challenge in communication.
      Informed consent was reportedly compromised due to language barriers by 29 per
      cent of respondents. Recommendations to improve communication included access to
      interpretation services, dentist technique/attitude to communication and patient
      preparedness for English-speaking encounters. CONCLUSIONS: Many respondents do
      not utilize the preferential communication methods, creating a potential
      compromise to both informed consent and the patients' best interests. The use of
      professional interpreters is recommended, and discussion should be supplemented
      with means of non-verbal communication. Dentists require access to lists of
      multilingual dentists and greater awareness of interpretation services to improve
      multilingual dentist-patient communication.

PMID- 17016889
TI  - An in vitro model to measure the effect of a silver fluoride and potassium iodide
      treatment on the permeability of demineralized dentine to Streptococcus mutans.
AB  - BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been
      used to reduce the incidence of caries in primary dentitions but has been limited
      by the associated staining of both teeth and restorative materials. The
      application of potassium iodide (KI), following AgF prevents staining but its
      effects on the ability of AgF to reduce caries are not known. The aim of this
      study was to develop an in vitro model that would provide an indication of the
      permeability of demineralized dentine to Streptococcus mutans after treatment of
      the dentine with AgF followed by KI. METHODS: Forty dentine discs were bonded to
      the base of forty 5mL polycarbonate screw top vials (that had had their bases
      removed), filled with nutrient medium, sterilized and placed into a continuous
      culture of S. mutans. Samples were divided into four groups as follows: 10
      samples of demineralized dentine as a control, 10 samples of demineralized
      dentine treated with AgF/KI, 10 samples of demineralized dentine treated with KI
      and 10 samples of demineralized dentine treated with AgF. After two weeks the
      optical density of the growth medium chambers was measured to determine bacterial
      penetration and growth. Cultures were plated out to determine migration through
      the discs by S. mutans. RESULTS: S. mutans migrated through all dentine discs.
      However, the samples treated with AgF and AgF/KI had significantly lower optical
      densities than the corresponding controls. The range of optical densities was
      least amongst demineralized samples treated with AgF/KI. CONCLUSIONS: Under the
      conditions of this study, treatment of demineralized dentine discs with AgF
      followed by KI allowed the penetration of S. mutans. Based on optical density
      measurements, the treatment resulted in significantly fewer microorganisms being
      present subjacent to the discs treated with AgF and KI than the control discs at
      the end of the experimental period.

PMID- 17016890
TI  - Microhardness and Ca:P ratio of carious and Carisolv treated caries-affected
      dentine using an ultra-micro-indentation system and energy dispersive analysis of
      x-rays--a pilot study.
AB  - BACKGROUND: This study aimed to evaluate microhardness and chemical analysis of
      carious and caries-affected dentine. The hypothesis tested was that
      calcium:phosphorous (Ca:P) ratios correlate with microhardness values. METHODS:
      Four carious human third molars were sectioned through the caries lesion in the
      mesiodistal longitudinal plane. One half of each lesion underwent carious dentine
      removal using Carisolv gel. The cut surfaces were polished, microhardness tested
      using an Ultra-Micro-Indentation System (UMIS) and elemental analysis performed
      using energy dispersive analysis of x-rays (EDAX). RESULTS: The microhardness of
      carious dentine decreased gradually towards the cavity floor, but that for caries
      affected dentine showed more variation with depth, having a mean hardness of
      (0.63 +/- 0.18) GPa. Ca:P ratios of carious dentine varied among the four
      specimens. The mean Ca:P ratio of caries-affected dentine was 1:2.03 +/- 0.08.
      The hypothesis was accepted for active lesions. CONCLUSIONS: The use of Carisolv
      to excavate carious tissue can be as effective as rotary instrumentation.

PMID- 17016891
TI  - Uptake of rotary NiTi technology within Australia.
AB  - BACKGROUND: Rotary NiTi technology was introduced into Australia approximately 10
      years ago. Little information is available in the dental literature to explain
      the adoption of new technology in dentistry. The aim of this paper is to identify
      and describe demographic features in the uptake of rotary NiTi technology within
      Australia. METHODS: In 2001, a questionnaire survey was mailed to a stratified
      systematic sample of general dentists and endodontists in Australia. The numbers
      of dentists in each state adopting the new technology were recorded and the
      results tabulated and graphed. RESULTS: The response rate for the survey was 87
      per cent. Overall, 26 per cent of responders used rotary NiTi instruments with a
      significantly higher proportion of endodontists (64 per cent) than general
      dentists (22 per cent). A significantly lower proportion of South Australian
      metropolitan general dentists used rotary NiTi compared with metropolitan
      dentists in all other states combined. The rate of uptake by South Australian
      dentists was lower than the other states. A significantly higher proportion of
      Queensland endodontists were using rotary NiTi compared with endodontists in New
      South Wales. A significantly greater proportion of rural dentists had tried and
      abandoned the new technology than metropolitan dentists. CONCLUSIONS: The
      adoption of rotary NiTi in Australia appears to conform to diffusion of
      innovation theory and has reached a critical mass making it self-sustaining.

PMID- 17016892
TI  - Pre-school child oral health in rural Western Australia.
AB  - BACKGROUND: In light of the various challenges faced by public dental health
      services, especially when large geographical areas and isolated communities are
      concerned, targeting of high risk groups within these populations needs to be
      investigated. This study aimed to assess caries experience, dental health
      behaviour and dental service utilization among a sample of pre-school children in
      a rural community in Western Australia. METHODS: The study was a cross-sectional
      oral health survey of pre-school children between the ages of 2 and 5 in
      Carnarvon, Western Australia. RESULTS: In total, 70 pre-school children
      (representing approximately 15 per cent of the total 2-5 year old population of
      Carnarvon) were examined. Less than half of the children were caries free. Both
      caries prevalence and severity (mean dmft) were significantly higher among
      Aboriginal children than non-Aboriginal children. Caries prevalence and severity
      were also significantly higher among children who often consumed carbonated
      drinks. CONCLUSIONS: This survey indicates that some pre-school children in rural
      areas, and especially Aboriginal pre-school children, are at high risk of
      developing dental caries. Effective oral health programmes commencing well before
      the usual first contact with dental services at age 5 are needed for young
      children at high risk of dental caries.

PMID- 17016893
TI  - The ability of 1.23% acidulated phosphate fluoride gel to inhibit simulated
      endogenous erosion in tooth roots.
AB  - BACKGROUND: Endogenous dental erosion is that produced by contact of gastric
      acids with tooth structure. It may affect exposed root cementum/dentine as well
      as coronal enamel, causing marked loss of mineral. The aim of this study was to
      determine whether 1.23 per cent acidulated phosphate fluoride gel, if applied to
      the surface cementum at certain intervals during an erosive acid challenge, could
      provide any protection against demineralization. MATERIALS AND METHODS: Roots of
      preserved extracted human teeth were painted with a water and acid resistant
      varnish, leaving two windows (3x1mm) of exposed dentine. These were placed in a
      solution containing 0.06MHCl and 2.2mMCaHPO4, which has been shown to simulate
      gastric acid when it meets the tooth surface. The roots were placed in the
      erosive solution unprotected (controls), or subject to APF application for four
      minutes prior to and every 10, 30 or 120 minutes during the erosive challenge.
      Roots were removed at either 6 or 12 hours, washed thoroughly and cut into
      120microm thick sections. Depths of demineralization were measured using an
      optical graticule under polarized light microscopy. RESULTS: A high level of
      protection was provided when the roots were coated with APF gel every 10 or 30
      minutes. CONCLUSIONS: APF gel will partially inhibit endogenous erosion of roots
      for up to 30 minutes if applied, for example, the night before a morning reflux
      episode. This should be considered along with other erosion control or reduction
      procedures for patients suffering from the effects of endogenous erosion.

PMID- 17016894
TI  - Tooth follicle extirpation and uvulectomy.
AB  - Migration is not only the movement of people, but also of their culture, customs
      and beliefs. As more people from developing countries in Africa migrate to
      industrialized countries, the more likely health professionals will find
      themselves providing care for people of whose customs and practices they have
      little knowledge. This review of the literature suggests that removal of
      deciduous canine follicles and uvulectomy are frequently practised in some
      African and neighbouring countries. Reasons given for deciduous canine
      extirpation include the prevention of vomiting, fever and diarrhoea. The
      indications for uvulectomy appear widespread, including treatment for persistent
      fever, coughing and growth retardation. The practices are usually performed by
      traditional healers. Risks for children who undergo these procedures are
      extensive, including septicaemia, potential for HIV transmission, numerous dental
      complications and death. With improved understanding between Western health teams
      and local, traditional people, an improved system may develop whereby the two
      systems can work together in providing improved health outcomes for the people.

PMID- 17016895
TI  - Doxycycline-induced staining of permanent adult dentition.
AB  - BACKGROUND: Doxycycline is the most effective antibiotic for managing
      brucellosis. Although it is relatively free from side effects, complications
      involving the skin, nails and teeth may rarely be encountered. METHODS: Four
      patients with brucellosis developed yellow-brown discolouration of teeth
      following a 30-45 day course of doxycycline therapy during summer at a dose of
      200mg/day. RESULTS: All four patients were diagnosed as having doxycycline
      induced staining of the permanent dentition. In all cases, the staining
      completely resolved and the teeth recovered their original colour following
      abrasive dental cleaning. CONCLUSIONS: These observations indicate that the
      incidence of staining of the permanent dentition, as a complication of
      doxycycline, may be much higher than the literature indicates, especially if
      treatment is administered during summer months. Fortunately, this complication is
      reversible and does not require termination of doxycycline therapy. Complete
      resolution following abrasive cleaning may suggest that an extrinsic mechanism
      within the dental milieu may be involved in its pathogenesis. Strict avoidance of
      sunlight exposure during high-dose, long-term doxycycline therapy might prevent
      the development of this complication.

PMID- 17016896
TI  - Extensive bleeding during surgical treatment for gingival overgrowth in a patient
      on haemodialysis--a case report and review of the literature.
AB  - Before performing renal transplantation, a most important concern is to control
      any infection, including oral infections before transplantation. The bleeding
      diathesis of patients with uraemia is a significant clinical concern, especially
      when surgery is required. A 44-year-old female patient on haemodialysis was
      referred for evaluation of gingival overgrowth. The patient was planning a renal
      transplantation two months later. As the lesions were not considered successfully
      treatable before transplantation, a gingivectomy and teeth extraction was
      performed. In pre-operative examinations, an abnormal bleeding time was not
      detected and other coagulation tests were normal. Under general anaesthesia, 19
      teeth were extracted and overgrown gingiva was removed. During the operation,
      extensive blood loss of 1650ml occurred and four units of concentrated red blood
      cells were transfused. This study suggests that patients with renal failure
      undergoing dental surgery require careful pre-surgical evaluation including
      assessment of their coagulation ability.

PMID- 17016897
TI  - Oral health and access to dental care in Australia--comparisons by cardholder
      status and geographic region.

PMID- 17016898
TI  - Mental illness and community care: a case for research.

PMID- 17016899
TI  - The efficacy of family intervention in adolescent mental health.
AB  - The term 'family therapy' is used to encompass a range of approaches that share a
      common view about the importance of family involvement in psychiatric disorders.
      This paper reviews the effectiveness of family interventions in adolescent mental
      health with a special emphasis on single session therapy. Research evidence shows
      that the family intervention in psychiatric disorders such as schizophrenia,
      depression, attention deficit hyperactive disorder, anxiety and anorexia not only
      provides better outcomes, but also increases client satisfaction with services.
      Among the family therapy approaches, single session therapy (SST) seems to be a
      flexible and very effective model for adolescent mental disorders, which seem to
      offer an efficient means of providing rapid access to services whilst removing
      some of the difficulties associated with other forms of family therapy
      approaches. A new service development model is also discussed by drawing together
      a number of ideas encountered in practice settings.

PMID- 17016900
TI  - The association between meaning of caregiving, perceived social support and level
      of depression of Taiwanese caregivers of mentally ill patients.
AB  - Caregiving is a demanding responsibility. Because of the de-institutionalization
      movement, much of the care provided by hospitals has been shifted to the
      community. Caregivers' issues cannot be overlooked. The purposes of the study
      are: (a) to understand meaning of caregiving, perceived social support and level
      of depression of caregivers during the transition phase immediately following a
      family members' discharge from the hospital to the community; (b) to determine
      the association between determinants and meaning of caregiving, perceived social
      support level of depression; (c) to determine the association between meaning of
      caregiving, perceived social support level of depression. Fifty five caregivers
      of schizophrenic patients were recruited from a private hospital in Taipei,
      Taiwan. Certain characteristics of caregivers were found to be associated with
      lower levels of depression, meaning of caregiving and perceived social support.
      Perceived social support was shown to be a mediator between the meaning of
      caregiving and caregivers' level of depression. Despite the small sample size,
      the findings can serve as a reference for mental health professionals as they
      develop mental health care program for patients and also for caregivers.

PMID- 17016901
TI  - Rethinking the benefits of an adapted version of 'Alzheimer Cafe' for individuals
      with Alzheimer's and their partners.
AB  - This article reviews dementia care in the context of an adapted version of an
      Alzheimer's Cafe focusing on eight couples newly diagnosed with dementia. It is
      primarily a reflective account. The adapted version of an Alzheimer Cafe focused
      on providing an informal cafe with more emphasis on communication, education and
      support for couples. It also seeks to provide a critical platform to evaluate the
      impact of developing such approaches like, (Alzheimer Cafe) in contrast to other
      approaches like, couple therapy, relationship and person centred approaches.

PMID- 17016902
TI  - The Centre for Psychiatric Nursing Research and practice: promoting excellence in
      psychiatric nursing.
AB  - The Centre for Psychiatric Nursing Research and Practice (CPNRP), is funded by
      the Department of Human Services Victoria, as an initiative to support
      psychiatric nurses throughout the State of Victoria. At the time of the CPNRPs
      inception in 1999, psychiatric nursing had been affected by widespread changes in
      the delivery of mental health services and nursing education in Victoria. The aim
      of this paper is to provide an overview of the development of the CPNRP and how
      this development reflected the significant issues of the time. The CPNRP
      introduced a number of programs and other initiatives in response to six primary
      issues: recruitment, retention, leadership, professional development, research:
      practice gap and communication.

PMID- 17016903
TI  - [Rubomycin microincapsulation with biodegradable polymer matrix].
AB  - A procedure for preparation of microspheres from biodegradable linear polyether
      of microbiological origin (polyhydroxybutirate, PHB) with using the technology of
      solvent evaporation was developed considering a specific example of two- and
      three-component emulsions. The procedure provided permanent preparation of the
      microspheres of high quality. The influence of the procedure (emulsion type,
      dispersion process and medium temperature) on the yield of the microspheres,
      their structure and size was shown. The temperature had a significant impact on
      incorporation of the antitumor anthracycline antibiotic daunorubicin (rubomycin)
      to the polymer matrix. The microspheres with various levels of the drug load (29
      and 90% of the initial content in the emulsion) were prepared and the kinetics of
      the in vitro rubomycin release was studied. The dynamics of the highly toxic
      rubomycin release from the microspheres was on the whole even with the curve
      profile reaching the plateau in 20-22 hours of the observation period. The rate
      of the rubomycin release to the medium depended on the value of the antibiotic
      incorporation and was maximum within the first two hours (3.3 and 13.0 mcg/ml.h)
      that corresponded to the release of 0.97 and 3.89 of the incorporated antibiotic.
      The average rate of rubomycin release during 300 hours was 0.81 x 10(-4) and 2.3
      x 10(-4) mcg/ml x h. The release constituted respectively 3.9 and 13.11% of the
      antibiotic incorporated to the microspheres.

PMID- 17016904
TI  - [Synthesis and antibacterial activity of new polyfluoro-1,3,5-oxadiazines].
AB  - A number of polyfluro-3,6-dihydro-2H-1,3,5-oxadiazines and polyfluoro-4H-1,3,5
      oxadiazines was designed. Relationship between their chemical structure and in
      vitro activity was investigated. The highest activity against grampositive
      microorganisms was shown by N1,N6-bis-[2,2,6,6-tetrakis(trifluoromethyl)-3,6
      dihydro-2H-1,3,5-oxadiazine-4-yl]-1,6-hexane diamine.

PMID- 17016905
TI  - [Development and estimation of nanosomal rifampicin].
AB  - A lab-scale method for preparation of rifampicin-loaded polybutylcyanoacrylate
      nanoparticles (nanosames) was developed. The biodistribution of the nanosome
      entrapped rifampicin after its intravenous administration was studied on healthy
      mice. The nanoparticles provided significant liver and spleen accumulation of
      rifampicin. Modification of the nanoparticles surface with poloxamer 407 or
      poloxamine 908 led to optimization of the biodistribution: the concentrations of
      rifampicin in the lungs and plasma increased, whereas the liver accumulation
      decreased vs. the unmodified nanoparticles. The increased lung accumulation of
      rifampicin enhanced bacterial clearance in the lungs of the mice infected with M.
      tuberculosis. The results showed that the use of the nanoparticles for
      optimization of the drug biodistribution was effective for increasing the
      efficacy of antiinfective chemotherapy.

PMID- 17016906
TI  - [Experimental study on the therapeutic effect of liposome-entrapped antibiotics
      in the treatment of destructive pneumonia].
AB  - The data on preparation of liposome-entrapped gentamicin sulfate and cefoperazone
      and their investigation on albino mice with staphylococcal destructive pneumonia
      are presented. Comparative study of the efficacy of gentamicin sulfate and
      cefoperazone in free and liposome-entrapped forms showed that immobilization of
      the antibiotics in phospholipid vesicles provided a 2-fold increase of their
      efficacy.

PMID- 17016907
TI  - [Isepamycin in prophylaxis and treatment of experimental plague due to FI+ and FI
      variants of plague microbe].
AB  - The efficacy of isepamycin vs. other aminoglycosides was studied in vitro and on
      albino mice with experimental plague due to natural antigen valuable strains of
      the plague microbe and the pathogen variants deprived of the ability to produce
      the capsular antigen fraction I (FI- phenotype). The MICs of isepamycin for the
      strains of the plague microbe (20 FI+ and 20FI-) were 1.0-4.0 mg?l, that did not
      differ from those of streptomycin, kanamycin, amikacin and tobramycin. The ED50
      of isepamycin in the prophylaxis and treatment of the experimental plague of the
      mice had no statistically significant differences from the ED50 of the other
      aminoglycosides. The efficacy index of isepamycin was > 10(4), that did not
      differ from that of streptomycin, amikacin and gentamicin, irrespective of the
      strain phenotype (Y. pestis 231 FI+ or Y. pestis 231 FI-). The same as the other
      aminoglycosides, isepamycin in doses equivalent to the human average daily doses,
      protected 80-100% of the albino mice from death when used in the prophylaxis and
      therapy of plague irrespective of the strain phenotype. The results of the study
      made it possible to consider isepamycin as an agent promising for the prophylaxis
      and treatment of plague.

PMID- 17016908
TI  - [Preclinical investigation and standardization of metronidazole soft dosage
      forms].
AB  - Comparative acute and subacute toxicity of Dentamet gel and Metrovagin
      suppositories manufactured by ZAO Altaivitaminy was studied with using analogous
      drugs, i. e. Metrogil Denta, a gel for the gingivae, manufactured by Unique
      Pharmaceutical Laboratories (India), and Flagil manufactured by Haupt Farma
      Livron (France) as the reference drugs. It was shown that the drugs induced no
      changes in the exterior, hair state, body weight and mobility of the experimental
      animals vs. the control. The pharmacokinetic study of Metrovagin vaginal
      suppositories vs. the registered analogous drug Flagil showed that Metrovagin was
      bioequivalent to Flagil. The relative bioavailability of the new drug vs. the
      control was 103.13%.

PMID- 17016909
TI  - [Taxonomic characterization and antibiotic resistance of pathogens of perinatal
      infectious inflammatory pathology in infants in Orenburg].
AB  - The materials on regional features of the nosologic structure, taxonomic spectrum
      and antibiotic resistance of the pathogens of perinatal infectious inflammatory
      pathology (IIP) in infants in Orenburg are presented. From 2002 to 2005 the
      average level of IIP of 19.0 cases per 1000 living new borns and the dominance of
      skin inflammatory diseases (vesiculopustulosis in particular) in the nosologic
      structure among the other forms of IIP (including conjunctivitis and pneumonia)
      were observed. The prevalence of the gram positive cocci with the leadership of
      coagulase negative staphylococci among the skin and eye forms of IIP was shown.
      Their portion reached 62.8%. The portion of the other microorganisms was much
      lover. Gramnegative bacteria (Neisseria spp., E. coli, K. ozaenae) were isolated
      from 6.1, 4.3 and 0.6% of the cases. The Candida isolates were detected in 1% of
      the cases. The regional antibiotic resistance register for the pathogens of IIP
      was developed. Its use is obligatory in prescribing drugs for empirical therapy
      of such pathology and prevention of its complications.

PMID- 17016910
TI  - [Activity of 22 antibacterials against O1 and O139 serogroup Vibrio cholerae
      strains isolated from humans within 1927-2005 in various regions of the world].
AB  - Analysis of antibioticograms of 390 O1 and O139 serogroup Vibrio cholerae strains
      isolated from humans within 1927-2005 in various regions of the world showed that
      the strains of V. cholerae isolated within 1927-1966 were susceptible to 22
      antibacterials, the strains isolated within 1938-1993 possessed 1-3 resistance
      markers and the strains isolated within 1994-2005 had 3-8 resistance markers
      including resistance to fluoroquinolones. All the strains of O139 serogroup V.
      cholerae isolated in 1993 and 1994 possessed 3 resistance markers. Studies on
      albino mice with generalized experimental cholera due to the V. cholerae eltor 1
      strain (P-18826, 2005) isolated from a cholera patient, which was highly
      resistant to nalidixic acid, streptomycin, ampicillin and
      trimethoprim/sulfamethoxazole and showed cross resistance to fluoroquinolones
      (ciprofloxacin, ofloxacin, pefloxacin and norfloxacin) and moderate resistance to
      ceftriaxone and cefotaxime, revealed that the only efficient antibiotics were
      tetracyclines and aminoglycosides (except streptomycin). The investigation
      demonstrated an extension of the antibiotic resistance spectra of the
      epidemically significant strains of the cholera pathogen and the necessity of
      using antibacterial drugs in strict accordance with the antibioticograms in
      emergent prophylaxis and therapy of cholera and immediate replacement of the drug
      by a more active one.

PMID- 17016911
TI  - [Problems of prevalance and resistance of nosocomial Klebsiella pneumonia in
      hospitals of Russia].
AB  - Prevalence of Klebsiella pneumoniae among gramnegative pathogens of nosocomial
      infections in intensive care units of 33 hospitals of 22 towns in Russia was
      investigated. Antibiotic susceptibility and extended-spectrum beta-lactamase
      production were tested in 420 nosocomial K. pneumoniae isolates. Carbapenems
      (imipenem, meropenem and ertapenem) showed the highest activity. Extended
      spectrum beta-lactamase production based on the phenotyping methods was revealed
      in 342 (81.4%) isolates. The maximum activity against the K. pneumoniae isolates
      producing extended-spectrum beta-lactamase was observed in imipenem and meropenem
      (no unsusceptible strains were isolated). 3.2% of the isolates was not
      susceptible to ertapenem. Differences in the activity of cefoperazone/sulbactam,
      amikacin, ciprofloxacin and levofloxacin against the extended-spectrum beta
      lactamase producing isolates in various hospitals were recorded.

PMID- 17016913
TI  - [Natural peptides with antimicrobial and immunomodulating activity].

PMID- 17016912
TI  - [Therapy of urinary tract infections in patients with diabetes mellitus].
AB  - Clinical and microbiological efficacy of Cifran OD (Ranbaxy, India), a
      formulation with prolonged action and extended release of ciprofloxacin was
      studied in 22 patients with bacteriuria and lingering diabetes mellitus.
      Ciprofloxacin was used in doses of 500 or 1000 mg orally once a day depending on
      the severity of the disease singns for 2-3 weeks as etiotropic therapy and only
      in 2 cases with severe pyelonephritis it was used intravenously drop-wise and
      orally simultaneously. Twenty eight microbial strains isolated from urea of the
      patients were tested. The main species of the isolates belonged to the family
      Enterobacteriaceae. Twenty five isolates (89.3%) were susceptible to
      ciprofloxacin and 3 isolates (10.7%) were resistant. The clinical efficacy of
      ciprofloxacin was 90.9%.

PMID- 17016914
TI  - [Candiduria: problems of diagnosis and therapy].
AB  - Candiduria is rather common. Yeasts could be detected in urine that was
      contaminated during collection of the specimens in patients with urinary bladder
      colonization or the upper urinary tract infection due either to retrograde spread
      of the pathogen from the urinary bladder or hematogenous dissemination from a
      distant infection focus. Most patients with candiduria are asymptomatic. The rate
      of complications is not known but appears to be low since candidemia rarely
      results from asymptomatic candiduria unless obstruction is present or
      instrumental examination of the urinary tract was performed. Unfortunately, there
      are no reliable diagnostic tests distinguishing fungal infection and
      colonization. Guidelines for antifungal therapy of candiduria, based almost
      entirely on fantastic reports and expert opinions, rather than on controlled
      clinical trials, were proposed by the Infectious Diseases Society of America.
      Until reliable methods for distinguishing infection from colonization are
      developed, further use of antifungal therapy is unlike to provide information for
      clinicians on the pathogenesis and effective treatment of candiduria.

PMID- 17016915
TI  - Marine halogenated natural products of environmental relevance.
AB  - A wide range and steadily increasing number of halogenated natural products
      (HNPs) is detected in marine organisms that are not the natural source of these
      compounds but which have accumulated these HNPs in a similar way as known to
      occur with anthropogenic halogenated pollutants such as PCBs and DDT. The HNPs
      have aromatic, aliphatic, and heterocyclic spines and are brominated,
      chlorinated, or mixed halogenated (Cl and Br). The exact isomer structures of
      HNPs are often closely related to the anthropogenic POPs, and for some compounds
      both natural and anthropogenic sources are likely to exist. Some of the HNPs are
      nonpolar, persistent, and can thus be found even in marine mammals and birds of
      prey. The most important HNPs detected in top predators are halogenated 1,1'
      dimethyl-2,2'-bipyrroles (HDBPs), the heptachloro-1'-methyl-1,2'-bipyrrole Q1,
      the tetrabromophenoxyanisole isomers 6-MeO-BDE 47 and 2'-MeO-BDE 68, and related
      compounds. Each of these compounds has been detected in higher trophic biota with
      concentrations exceeding 1 mg/kg.

PMID- 17016916
TI  - Heavy metals remediation of water using plants and lignocellulosic agrowastes.
AB  - Toxic heavy metals and metalloids are constantly released into the environment,
      and their removal is a very difficult task because of the high cost of treatment
      methods. Various methods exist for the removal of toxic metal ions from aqueous
      solutions. Among these are adsorption using activated carbon, by far the most
      versatile and widely used method for the removal of toxic metals; however, it is
      relatively expensive and less feasible to use in developing countries.
      Furthermore, activated carbon loaded with toxicants is generally incinerated or
      disposed of on land, thereby causing environmental pollution through different
      routes. There is an urgent need to develop low-cost, effective, and sustainable
      methods for their removal or detoxification. The use of lignocellulosic
      agrowastes is a very useful approach, because of their high adsorption
      properties, which results from their ion-exchange capabilities. Agricultural
      wastes can be made into good sorbents for the removal of many metals, which would
      add to their value, help reduce the cost of waste disposal, and provide a
      potentially cheap alternative to existing commercial carbons. Although the
      abundance and very low cost of lignocellulosic wastes from agricultural
      operations are real advantages that render them suitable alternatives for the
      remediation of heavy metals, further successful studies on these materials are
      essential to demonstrate the efficacy of this technology.

PMID- 17016917
TI  - Earthworm biomarkers in ecological risk assessment.
AB  - Earthworms have had a notable contribution in terrestrial ecotoxicology. They
      have been broadly used to assess environmental impact from metal pollution, and
      they are typical test organisms (e.g., Eisenia) in standardized toxicity tests.
      Several reviews and international workshops have stressed the need for increasing
      the understanding and applicability of earthworm biomarkers in the ecological
      risk assessment (ERA) process. This review summarizes recent available
      information concerning the most investigated earthworm biomarkers. In earthworms,
      the use of biomarkers has been focused on assessing metal pollution, and
      available data on biomarker responses to organic contaminants are rather limited.
      The potential for applying earthworm biomarkers in the standardized toxicity
      tests is suggested in view of their significant contribution to the risk
      assessment of contaminated soils (e.g., estimation of bioavailable and bioactive
      fraction or sublethal effects). Field studies involving earthworm biomarkers are
      still scarce and are summarized according to their main practical approaches in
      retrospective ERA: biological surveys, laboratory tests of the soil, simulated
      field studies, and in situ exposure bioassays. Despite the great volume of
      laboratory studies on earthworm biomarkers, future lines of research are
      suggested besides the recommendations made by others: (1) the potential and
      limitations of the inclusion of biomarkers in the standardized toxicity tests
      should be examined under a well-defined weight-of-evidence framework; (2) it is
      necessary to develop operating guidelines to standardize earthworm biomarker
      assays, an important step to apply biomarkers in a regulatory context; (3)
      molecular and physiological biomarkers should be directly linked to behavioral
      changes with significant ecological implications, an important step in
      considering them as ecotoxicological biomarkers; and (4) biomarkers to organic
      pollutants of current concern (e.g., polycyclic aromatic hydrocarbons, anti-ChE
      and pyrethroid insecticides, polybrominated flame retardants, etc.) need to be
      developed and validated in the field. Also, an increase in the knowledge of
      earthworm biomarkers is undoubtedly useful in assessing the effectiveness of
      procedures for recovering/protecting the environment (e.g., phytoremediation or
      agrienvironment schemes) besides its potential use in the ERA framework.

PMID- 17016918
TI  - Using soil health to assess ecotoxicological impacts of pollutants on soil
      microflora.
AB  - Microorganisms are essential for a properly functioning soil ecosystem. However,
      few methods allow an ecotoxicological evaluation of pollutant impact on the soil
      microbial community. This review proposes the use of the concept of soil health
      as an ecotoxicological evaluation tool for soil microflora. Initially limited to
      sustainable agriculture, the concept of soil health is now being applied to novel
      situations including contaminated and remediated soils. A large amount of work
      has been published in the last few decades on soil health indicators, and a
      review of the most relevant studies is presented here. The most cited work is
      that of the S-5518 committee set up in 1997 by the Soil Science Society of
      America (SSSA), which proposed to define soil quality as being "the capacity of a
      soil to function within the limits of an ecosystem, to support biological
      production, to maintain environmental quality and to support fauna and flora
      health." The soil health indicators reviewed here are the ones based on this
      definition because it relates well to sustainability and durability of the soil
      functions. Several indicators proposed in these studies could be employed in the
      evaluation of the ecotoxicological impact of pollutants on the soil microbial
      community, including microbial diversity, microbial activity, and functional
      stability. However, research is still required to unify the concept, to set
      threshold values, and to standardize methodologies.

PMID- 17016919
TI  - Adsorption of ionisable pesticides in soils.
AB  - Understanding the fate of a pesticide in soil is fundamental to the accurate
      assessment of its environmental behaviour and vital in ensuring the safe use of
      new and existing products. Ionisable pesticides comprise a significant proportion
      of both existing and new active substances registered for use in agriculture
      worldwide. This group of pesticides includes chemicals that are frequently found
      in groundwater and surface waters in many different countries. Despite this,
      approaches to predict the influence of soil properties on the behaviour of
      ionisable pesticides in soils are poorly developed. Current regulatory
      assessments frequently default to methods developed for nonionic chemicals,
      although it is evident that ionisable compounds do not often react like neutral
      molecules. This review presents the state of knowledge on the adsorption of
      ionisable pesticides in soils. It first introduces the issues concerning
      adsorption and the characteristics of this particular kind of chemical. The
      mechanisms postulated for the adsorption of ionisable pesticides are then
      described: these are hydrophobic partitioning, ionic exchange, charge transfer,
      ligand exchange, cation or water bridging, and the formation of bound residues.
      Relatively little experimental evidence is available, and we are still unable to
      determine the quantitative contribution of each process in a particular
      situation. Knowledge is still lacking concerning phenomena occurring at the
      surfaces of soil particles. Measurements do not allow determination of the
      operative pH at the surface of soil particles or in microenvironments, and the
      influence of ionic strength or competition effects is difficult to assess.
      Subsequently, the review focuses on the influence of soil properties on
      adsorption and on potential to predict the behaviour of ionisable pesticides in
      soils. Unlike hydrophobic compounds, adsorption of ionisable pesticides is highly
      sensitive to variation in pH. This relationship mainly derives from the different
      proportion of ionic and neutral forms of the pesticide present at each pH level
      but also from the presence of surfaces with pH-dependent charges in soils. Soil
      organic matter generally promotes adsorption, although a negative influence has
      sometimes been reported. Clay and oxides can also play a significant role in some
      cases. So far, no modelling approach has been applied successfully to a range of
      ionisable pesticides to predict their adsorption in soils. The standardization of
      experimental settings and the application of approaches specific to a particular
      class of pesticide or different type of soil might be necessary to describe the
      complexity of interactions among ionisable molecules. Degradation of ionisable
      pesticides is influenced by soil pH in a particular way that relates to changes
      in sorption, changes in composition and activity of the microbial community, and
      to shifts in the balance between different degradative mechanisms.

PMID- 17016920
TI  - [Merkel cell carcinoma].
AB  - Merkel cell carcinoma (Mcc) is a very rare, malignant, neuroendocrine tumour. Mcc
      has an aggressive behavior, local recurrence, and regional or distant metastasis
      generally develop within a short period of time. At the Oral Medicine Department
      158,056 patients were treated between 1970 and 2004. A single case of Mcc was
      diagnosed, in a 79-year-old woman. The tumour was localized to the upper lip.
      After successful cryosurgery and a 7-year tumour-free period, a new tumour
      developed in her palatine tonsil. It was an anaplastic carcinoma with
      neuroendocrine features, raising the possibility of a late haematogenous
      metastasis, a second field tumour, or a second primary tumour. The clinical,
      histological, immunohistochemical and genetic findings suggested that the tumour
      of the palatine tonsil is a second field tumour.

PMID- 17016921
TI  - [A biomechanical study of the mechanical stress transmission of dental implants
      using finite element analysis. Review of literature. Part I].
AB  - Finite Element Analysis (FEA) is a computerised investigative method that is
      capable of determining the mechanical stress arising in various objects and their
      environment as a result of forces effecting the system by using a mathematical
      model. The method is most often used for purposes of technical, engineering
      design, but is very useful for medical purposes-the static and functional
      investigation of the skeletal and motor system of the human body-as well. The
      transmission of mechanical stress between the implant and bone depends on a
      number of factors, and its description is quite complicated. A model has to be
      created to perform a FEA, the geometric data of the implant, the mechanical
      properties of the bone and the parameters of the bone-implant interface have to
      be determined, a so-called finite element network has to be created. Valuable
      data can be obtained by changing the individual elements of the system. The study
      of dental implants makes it possible to better investigate biomechanical
      conditions and thus the further perfection of implant methods. In the first part
      of the present two-part publication authors review the possibilities of use of
      the finite element analysis in examining the stress transmission of dental
      implants. In the second part of the publication their own studies will be
      presented.

PMID- 17016922
TI  - [Malignant melanoma metastasis in the oral cavity].
AB  - Malignant melanoma occurs only rarely as a primary tumour in the oral cavity,
      with an incidence of 1-2 percent. Oral melanomas are predominantly to be found in
      the hard and soft palate, and less often in the gingiva and mandible. Mucosal
      malignant melanomas are much more aggressive than those situated in the skin. In
      two-thirds of the cases the route of formation of the metastases is lymphogenic,
      and haematogenic in the remainder. The typical sites of the distant metastases
      are the skin, the lungs, the brain, the liver, and the bones. Metastatic
      malignant melanoma in the oral cavity, a rarity in the literature, is associated
      with a very poor prognosis. This paper reports on two cases in which an isolated
      distant metastasis developed in the oral cavity.

PMID- 17016923
TI  - [Problems with working length determination during endodontic therapy].
AB  - Accurate working length (WL) determination is a crucial part of successful root
      canal therapy. Working length is the distance from the coronal reference plane to
      the apical constriction. The apical constriction, also referred to as
      cementodentinal junction, represents the transition between the pulpal and the
      periodontal tissues. It is widely accepted that canal preparation and filling
      should be terminated at that point. However, the location and form of the apical
      constriction are variable and not always detectable. Moreover, the available
      clinical methods used for WL measurements are also inaccurate. At present two
      methods are recommended in dental practice for determination of WL: radiographic
      technique, and by the means of electronic apex locators. Advantages and
      disadvantages of the two methods are discussed in this paper.

PMID- 17016924
TI  - [Oral squamous sell carcinoma in North-Eastern Hungary I. Epidemiology].
AB  - The purpose of this study was to characterize the epidemiological data of oral
      squamous cell carcinoma (OSCC) patients in North-Eastern Hungary. The medical
      records of 119 randomly selected patients with OSCC admitted to the Department of
      Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were
      reviewed. Cases were identified according to the epidemiological data, as to
      site, tumor size, lymph node involvement, clinical stage, histological
      differentiation, treatment obtained, recurrence of disease and survival rate.
      There was an obvious male predominance (male:female = 5.2:1). The median age at
      diagnosis was 57.4 years. The most common sites of OSCC were the floor of the
      mouth (27.7%), the lip (26.9%) and the tongue (22.7%). The majority of the
      patients (58,8%) presented with early-stage (I-II) disease at the time of
      diagnosis, and 48.6% had moderately differentiated tumors. The most frequent
      therapeutic modality used was surgery with or with out of radiotherapy. Roughly
      one fifth of the cases (20.7%) experienced a recurrence of disease during the
      follow-up period. The overall 5-year survival rate was 38.7% (stage I: 68.3%,
      stage II: 31.0%, stage III: 22.6%, stage IV: 11.1%). There was a correlation
      between survival and tumor size, lymph node metastasis, clinical stage and
      surgical treatment (p < or = 0.05, respectively). We found no significant
      correlation between histological differentiation and survival. Clinical stage
      exerts the most strongly significant impact on survival. Therefore, early
      detection and proper surgical intervention enhance patients' survival most
      effectively.

PMID- 17016925
TI  - [The clinical importance of the mandibular canal course variations].
AB  - The authors review the literature relating to anatomical variations of mandibular
      canals. They compare the results of their examinations with the literature data.
      The proportion of duplicated mandibular canal observed during macroscopic
      examinations of mandibles proved to be substantially higher than that revealed by
      X-ray pictures. The knowledge of the course of the mandibular canal and its
      anatomical variations is of great importance in certain oral surgical
      interventions, such as preprosthetic operations and the insertion of enosseal
      implants, and during the planning of removable dentures prepared in cases
      involving extensively atrophied mandibles. The authors review the possible
      consequences of the injury of accessory mandibular canal.

PMID- 17016926
TI  - Hospital case payment systems in Europe.
AB  - Since the introduction of the system of diagnosis related groups (DRGs) for USA
      Medicare patients in 1983, case payment mechanisms have gradually become the
      principal means of reimbursing hospitals in most developed countries. The use of
      case payments nevertheless poses severe technical and policy challenges, and
      there remain many unresolved issues in their implementation. This paper
      introduces a special issue of the journal that describes and compares experience
      with the use of case payments for reimbursing hospitals in nine European
      countries. The editorial sets the policy scene, and argues that DRG systems must
      be seen both as a technical reimbursement method and as a fundamental incentive
      mechanism within the health system.

PMID- 17016927
TI  - Methods to determine reimbursement rates for diagnosis related groups (DRG): a
      comparison of nine European countries.
AB  - Over the past 20 years, most European countries have introduced DRGs or similar
      grouping systems as instruments for hospital reimbursement. This paper compares
      and analyzes the methods used to determine prices for inpatient care within DRGs
      or similar grouping systems employed in nine EU member states (i.e., Denmark,
      France, Germany, Hungary, Italy, Tthe Netherlands, Poland, Spain and England). It
      categorizes the systems of patient classification used in these nine countries
      and compares them according to the three steps necessary in order to set prices:
      1.) definition of a data sample, 2.) use of trimming methods and plausibility
      checks and 3.) definition of prices. It concludes with a discussion on the
      typical development path of DRG systems and the role of additional reimbursement
      components in this context.

PMID- 17016928
TI  - Cost accounting and public reimbursement schemes in Spanish hospitals.
AB  - The objective of this paper is to provide a description and analysis of the main
      costing and pricing (reimbursement) systems employed by hospitals in the Spanish
      National Health System (NHS). Hospitals cost calculations are mostly based on a
      full costing approach as opposite to other systems like direct costing or
      activity based costing. Regional and hospital differences arise on the method
      used to allocate indirect costs to cost centres and also on the approach used to
      measure resource consumption. Costs are typically calculated by disaggregating
      expenditure and allocating it to cost centres, and then to patients and DRGs.
      Regarding public reimbursement systems, the impression is that unit costs are
      ignored, except for certain type of high technology processes and treatments.

PMID- 17016929
TI  - Costs and prices for inpatient care in England: mirror twins or distant cousins?
AB  - The National Health Service (NHS) in England is introducing a national cost-per
      case tariff system for the reimbursement of hospital services. Unlike most other
      countries with similar payment mechanisms, hospitals in England will have few
      alternative sources of income once the tariff system is fully implemented. This
      new financial regime generates powerful incentives for change, but exposes
      purchasers and providers to considerable financial risks. This paper examines the
      structure of the tariff. We describe how costs are determined, analyse the extent
      to which prices reflect costs, and review the results of an early evaluation of
      the system.

PMID- 17016930
TI  - Cost accounting methodologies in price setting of acute inpatient services in
      Hungary.
AB  - On the basis of documentary analysis and interviews with decision makers, this
      paper discusses the cost accounting methodologies used for price setting of
      inpatient services in the Hungarian health care system focusing on sector of
      acute inpatient care, which is financed through the Hungarian adaptation of
      Diagnosis Related Groups since 1993. Hungary has a quite sophisticated DRG
      system, which had a deep impact on the efficiency of the acute inpatient care
      sector. Nevertheless, the system requires continuous maintenance, where the
      cooperation of hospitals, as well as the minimisation of political influence are
      critical success factors.

PMID- 17016931
TI  - Inpatient reimbursement system in Italy: how do tariffs relate to costs?
AB  - In 1995 the Italian National Health Service begun to fund its hospitals on a per
      case basis, classified according to a DRGs system. Five out of 21 Italian regions
      developed a regional DRG tariff system, while the majority adopted the system set
      at national level. The article presents how tariffs are set by the national
      government and by the Lombardy Region. Production cost (mainly assessed according
      to a top-down, gross-costing approach) is only one of the variables used for
      setting tariffs. Microcosting is not used and, apparently, is not deemed as an
      appropriate methodology. After 10 years since their introduction national and
      regional tariffs are still not derived from explicit algorithms.

PMID- 17016932
TI  - Variable prospective financing in the Danish hospital sector and the development
      of a Danish case-mix system.
AB  - This article aims to describe and assess the Danish case-mix system, the cost
      accounting applied in setting national tariffs and the introduction of variable,
      prospective payment in the Danish hospital sector. The tariffs are calculated as
      a national average from hospital data gathered in a national cost database.
      However, uncertainty, mainly resulting from the definition of cost centres at the
      individual hospital, implies that the cost weights may not fully reflect the
      hospital treatment cost. As variable prospective payment of hospitals currently
      only applies to 20% of a hospital's budget, the incentives and the effects on
      productivity, quality and equality are still limited.

PMID- 17016933
TI  - Cost accounting to determine prices: how well do prices reflect costs in the
      German DRG-system?
AB  - Germany has recently introduced a system of Diagnosis Related Groups (DRGs) to
      engender more appropriate resource allocation. The following article describes
      the German DRG-system and the methodologies used to determine prices. It analyses
      the extent to which prices, or calculated cost weights, reflect the actual costs
      incurred by hospitals for their respective services. We reveal that a
      "compression" of DRG cost weights occurs, and that the data sample used to
      calculate cost weights is lacking in terms of its representativeness. Although
      cost data accuracy has improved over the last few years there are still a number
      of challenges that need to be addressed.

PMID- 17016934
TI  - The definition of prices for inpatient care in Poland in the absence of cost
      data.
AB  - The health reform of 1999 in Poland introduced market-like relations in the
      health care sector. The oligopsonic and the current monopsomic position of the
      payer makes prices for health care products purchased in this quasi-market low
      and does not usually take into account the costs of production. Despite a long
      history of cost calculation in the system, a systematic and reliable assessment
      of costs is still lacking which would help in setting up fair financing. At the
      same time providers complain about the dictatorship of the National Health Fund
      (NHF) yet they rarely resign from contracts with the NHF when they have the
      chance to conclude one.

PMID- 17016935
TI  - Cost assessment and price setting of inpatient care in The Netherlands. the DBC
      case-mix system.
AB  - In February 2005, a case-mix system based on 'diagnosis treatment combinations'
      (DBCs) was introduced in The Netherlands for the registration and reimbursement
      of hospital and medical specialist care. This paper describes the characteristics
      of the DBC system and how it is used for the reimbursement of hospitals. Prices
      for reimbursement are either based on fixed tariffs ('list A') or negotiated
      between health insurers and hospitals ('list B') and are partly based on
      information about unit costs of health care services. Because the DBC system is
      still under development we will describe the current situation (March 2006), but
      also focus on the most likely future developments.

PMID- 17016936
TI  - Accounting and reimbursement schemes for inpatient care in France.
AB  - The new French case-mix system of hospital payment was adopted in 2004 for public
      hospitals and in March 2005 for private-for-profit hospitals. Implementing this
      reform requires a period of transition but the challenges ahead can already be
      predicted. Prices will have to change before this mode of reimbursement can have
      any real impact. This requires producing more detailed hospital cost data and
      using fine measuring tools such as the cost accounting method developed for use
      in this context. This article describes and analyses the main tools and methods
      selected to implement the new French prospective payment system.

PMID- 17016937
TI  - Does elevated blood pressure at the time of surgery increase perioperative
      cardiac risk? IMPACT consults. Proceedings of the 2nd Annual Cleveland Clinic
      Perioperative Medicine Summit.

PMID- 17016938
TI  - When is it appropriate to stop antiplatelet therapy in a patient with a drug
      eluting stent prior to noncardiac surgery? IMPACT consults. Proceedings of the
      2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016939
TI  - Should statins be discontinued preoperatively? IMPACT consults. Proceedings of
      the 2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016940
TI  - What is the appropriate means of perioperative risk assessment for patients with
      cirrhosis? IMPACT consults. Proceedings of the 2nd Annual Cleveland Clinic
      Perioperative Medicine Summit.

PMID- 17016941
TI  - Who is at risk for developing acute renal failure after surgery? IMPACT consults.
      Proceedings of the 2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016942
TI  - Obstructive sleep apnea: what to do in the surgical patient? IMPACT consults.
      Proceedings of the 2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016943
TI  - What is the optimal venous thromboembolism prophylaxis for patients undergoing
      bariatric surgery? IMPACT consults. Proceedings of the 2nd Annual Cleveland
      Clinic Perioperative Medicine Summit.

PMID- 17016944
TI  - Do hip fractures need to be repaired within 24 hours of injury? IMPACT consults.
      Proceedings of the 2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016945
TI  - Is postoperative atrial fibrillation in patients undergoing noncardiothoracic
      surgery an important problem? IMPACT consults. Proceedings of the 2nd Annual
      Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016946
TI  - How can postoperative ileus be prevented and treated? IMPACT consults.
      Proceedings of the 2nd Annual Cleveland Clinic Perioperative Medicine Summit.

PMID- 17016947
TI  - Hidden hunger and the role of public-private partnership.

PMID- 17016948
TI  - Combating hidden hunger: the role of international agencies.
AB  - The importance of micronutrient deficiencies or "hidden hunger" was clearly
      emphasized by the inclusion of specific goals on iron, vitamin A, and iodine
      deficiency at the 1990 World Summit for Children and other major international
      nutrition conferences. Significant progress has since been made toward
      eliminating vitamin A and iodine deficiencies, with less progress made toward
      reducing the burden of iron-deficiency anemia. The role of international
      agencies, such as the World Health Organization, United Nations Children's Fund,
      Food and Agricultural Organization, and World Bank in assisting countries to make
      progress toward the World Summit for Children goals has been very important.
      International agencies have played a critical role in advocating for and raising
      awareness of these issues at the international, regional, and national levels
      among policymakers and the general population. Using a rights-based approach,
      UNICEF and other agencies have been instrumental in elevating to the highest
      political level the discussion of every child's right to adequate nutrition.
      International agencies have also been very supportive at the national level in
      providing technical guidance for programs, including monitoring and evaluation.
      These agencies have played a critical role in engaging the cooperation of other
      partners, including bilateral donors, non-governmental organizations, and the
      private sector for micronutrient programs. Furthermore, international agencies
      provide financial and material support for micronutrient programs. In the future,
      such agencies must continue to be heavily involved in programs to achieve the
      newly confirmed goals for 2010. The present paper focuses on the role of
      international agencies in combating micronutrient deficiencies, drawing on the
      lessons learned over the last decade. The first section of the paper summarizes
      the progress achieved since 1990, and the second section describes the specific
      role of international agencies in contributing to that progress.

PMID- 17016949
TI  - Vitamin A deficiency disorders in children and women.
AB  - Vitamin A deficiency is an endemic nutrition problem throughout much of the
      developing world, especially affecting the health and survival of infants, young
      children, and pregnant and lactating women. These age and life-stage groups
      represent periods when both nutrition stress is high and diet likely to be
      chronically deficient in vitamin A. Approximately 127 million preschool-aged
      children and 7 million pregnant women are vitamin A deficient. Health
      consequences of vitamin A deficiency include mild to severe systemic effects on
      innate and acquired mechanisms of host resistance to infection and growth,
      increased burden of infectious morbidity, mild to severe (blinding) stages of
      xerophthalmia, and increased risk of mortality. These consequences are defined as
      vitamin A deficiency disorders (VADD). Globally, 4.4 million preschool children
      have xerophthalmia and 6 million mothers suffer night blindness during pregnancy.
      Both conditions are associated with increased risk of morbidity and mortality.
      While reductions of child mortality of 19-54% following vitamin A treatment have
      been widely reported, more recent work suggests that dosing newborns with vitamin
      A may, in some settings, lower infant mortality. Among women, one large trial has
      so far reported a > or = 40% reduction in mortality related to pregnancy with
      weekly, low-dose vitamin A supplementation. Epidemiologic data on vitamin A
      deficiency disorders can be useful in planning, designing, and targeting
      interventions.

PMID- 17016950
TI  - Iodine deficiency: consequences and progress toward elimination.
AB  - While traditionally associated with cretinism and goiter, iodine deficiency has
      broad effects on central nervous system development that can occur in the absence
      of either condition. Any maternal iodine deficiency results in a range of
      intellectual, motor, and hearing deficits in offspring. This loss in intellectual
      capacity limits educational achievement of populations and the economic prowess
      of nations. Progress made since the historic World Summit for Children in 1990
      has been outstanding. Approximately 70% of households in the world used iodized
      salt by 2000, compared with less than 20% in 1990. It is estimated that at least
      85 million newborns out of 130 million annual births are protected from a loss in
      learning ability that would otherwise have occurred. The elimination of iodine
      deficiency, by expedient production, marketing, and universal consumption of
      iodized salt, represents a significant development effort in public nutrition.
      Although globally iodine nutrition has greatly improved, 20% to 30% of
      pregnancies and thus newborns still do not fully benefit from the use of iodized
      salt. Countries where success is in evidence could rapidly revert back to
      deficiency if vigilance is not maintained. Just as success came through concerted
      public-private-civic actions, making sure that this is expanded and will steadily
      go on requires continuous collaboration.

PMID- 17016951
TI  - Iron deficiency: global prevalence and consequences.
AB  - Iron deficiency is considered to be one of most prevalent forms of malnutrition,
      yet there has been a lack of consensus about the nature and magnitude of the
      health consequences of iron deficiency in populations. This paper presents new
      estimates of the public health importance of iron-deficiency anemia (IDA), which
      were made as part of the Global Burden of Disease (GBD) 2000 project. Iron
      deficiency is considered to contribute to death and disability as a risk factor
      for maternal and perinatal mortality, and also through its direct contributions
      to cognitive impairment, decreased work productivity, and death from severe
      anemia. Based on meta-analysis of observational studies, mortality risk estimates
      for maternal and perinatal mortality are calculated as the decreased risk in
      mortality for each 1 g/dl increase in mean pregnancy hemoglobin concentration. On
      average, globally, 50% of the anemia is assumed to be attributable to iron
      deficiency. Globally, iron deficiency ranks number 9 among 26 risk factors
      included in the GBD 2000, and accounts for 841,000 deaths and 35,057,000
      disability-adjusted life years lost. Africa and parts of Asia bear 71% of the
      global mortality burden and 65% of the disability-adjusted life years lost,
      whereas North America bears 1.4% of the global burden. There is an urgent need to
      develop effective and sustainable interventions to control iron-deficiency
      anemia. This will likely not be achieved without substantial involvement of the
      private sector.

PMID- 17016952
TI  - Effect of iron-deficiency anemia on cognitive skills and neuromaturation in
      infancy and childhood.
AB  - Iron-deficiency anemia in infancy has been consistently shown to negatively
      influence performance in tests of psychomotor development. In most studies of
      short-term follow-up, lower scores did not improve with iron therapy, despite
      complete hematologic replenishment. The negative impact on psychomotor
      development of iron-deficiency anemia (IDA) in infancy has been well documented
      in more than a dozen studies during the last two decades. Two studies will be
      presented here to further support this assertion. Additionally, we will present
      some data referring to longer follow-up at 5 and 10 years as well as data
      concerning recent descriptions of the neurologic derangements that may underlie
      these behavioral effects. To evaluate whether these deficits may revert after
      long-term observation, a cohort of infants was re-evaluated at 5 and 10 years of
      age. Two studies have examined children aged 5 years who had anemia as infants
      using comparable tools of cognitive development showing persisting and consistent
      important disadvantages in those who were formerly anemic. These tests were
      better predictors of future achievement than psychomotor scores. These children
      were again examined at 10 years and showed lower school achievement and poorer
      fine-hand movements. Studies of neurologic maturation in a new cohort of infants
      aged 6 months included auditory brain stem responses and naptime 18-lead sleep
      studies. The central conduction time of the auditory brain stem responses was
      slower at 6, 12, and 18 months and at 4 years, despite iron therapy beginning at
      6 months. During the sleep-wakefulness cycle, heart-rate variability--a
      developmental expression of the autonomic nervous system--was less mature in
      anemic infants. The proposed mechanisms are altered auditory-nerve and vagal
      nerve myelination, respectively, as iron is required for normal myelin synthesis.

PMID- 17016953
TI  - Multiple-micronutrient fortification technology development and evaluation: from
      lab to market.
AB  - At the World Summit for Children (New York, 1990), a resolution was passed to
      eliminate vitamin A and iodine deficiencies and significantly reduce iron
      deficiency anemia by the year 2000. In responding to this urgent call, we
      developed a unique multiple-micronutrient fortification delivery system called
      "GrowthPlus/CreciPlus." Using this technology, a fortified powder fruit drink has
      been formulated and extensively evaluated. One serving of the product delivers
      the following US recommended dietary allowances: 20-30% of iron; 10-35% of
      vitamin A; 25-35% of iodine; 100-120% of vitamin C; 25-35% of zinc; 15-35% of
      folate; and 10-50% of vitamins E, B2, B6, and B12. This was accomplished through
      (a) identifying and selecting the right fortificants, and (b) understanding their
      chemical and physical properties that contribute to multiple problems (product
      acceptability, stability, and bioavailability). Data from a home-use test showed
      fortification with the "Multiple-Fortification Technology" has no effect on the
      appearance and taste of the eventually consumed powder fruit drink. One-year
      stability studies demonstrated that iodine and the vitamins have adequate
      stability. Bioavailability evaluation by using double-isotope labeling technique
      showed that the iron from the fortified powder drink has excellent
      bioavailability (23.4% +/- 6.7). In conclusion, a powder fruit drink has been
      clinically demonstrated to deliver multiple micronutrients, which include
      adequate levels of bioavailable iron, vitamin A, iodine, zinc, vitamin C, and B
      vitamins, without compromising taste, appearance, and bioavailability. The
      critical limiting step in the micronutrient fortification program is the
      production and distribution of the multiple-micronutrient-fortified product. The
      fortified powder drink was marketed in Venezuela under the brand name NutriStar.

PMID- 17016954
TI  - Efficacy trials of a micronutrient dietary supplement in schoolchildren and
      pregnant women in Tanzania.
AB  - Traditionally, the main strategies used to control micronutrient deficiencies
      have been food diversification, consumption of medicinal supplements, and food
      fortification. In Tanzania, we conducted efficacy trials using a dietary
      supplement as a fourth approach. These were randomized, double-blind, placebo
      controlled efficacy trials conducted separately first in children and later in
      pregnant women. The dietary supplement was a powder used to prepare an orange
      flavored beverage. In the school trial, children consumed 25 g per school day
      attended. In the pregnancy trial, women consumed the contents of two 25-g sachets
      per day with meals. This dietary supplement, unlike most medicinal supplements,
      provided 11 micronutrients, including iron and vitamin A, in physiologic amounts.
      In both trials we compared changes in subjects consuming either the fortified or
      the nonfortified supplement. Measures of iron and vitamin A status were similar
      in the groups at the baseline examination, but significantly different at follow
      up, always in favor of the fortified groups. Children receiving the fortified
      supplement had significantly improved anthropometric measures when compared with
      controls. At four weeks postpartum, the breast milk of a supplemented group of
      women had significantly higher mean retinol content than did the milk of mothers
      consuming the nonfortified supplement. The advantages of using a fortified
      dietary supplement, compared with other approaches, include its ability to
      control several micronutrient deficiencies simultaneously; the use of physiologic
      amounts of nutrients, rather than megadoses that require medical supervision; and
      the likelihood of better compliance than with the use of pills because subjects
      liked the beverage used in these trials.

PMID- 17016955
TI  - Effect of a multiple-micronutrient-fortified fruit powder beverage on the
      nutrition status, physical fitness, and cognitive performance of schoolchildren
      in the Philippines.
AB  - This study aimed to determine the effect of a multiple-micronutrient-fortified
      beverage on the micronutrient status, physical fitness, and cognitive performance
      of schoolchildren. The study was a randomized, double-blind, placebo-controlled
      trial of schoolchildren assigned to receive either the fortified or nonfortified
      beverage with or without anthelmintic therapy. Data on hemoglobin level, urinary
      iodine excretion (UIE) level, physical fitness, and cognitive performance were
      collected at baseline and at 16 weeks post-intervention. The fortified beverage
      significantly improved iron status among the subjects that had hemoglobin levels
      < 11 g/dl at baseline. The proportion of children who remained moderately to
      severely anemic was significantly lower among those given the fortified beverage.
      In the groups that received the fortified product, the median UIE level
      increased, whereas among those who received the placebo beverage, the median UIE
      level was reduced significantly. Iron- and/or iodine-deficient subjects who
      received the fortified beverage showed significant improvements in fitness (post
      exercise reduction of heart rate) and cognitive performance (nonverbal mental
      ability score). The study showed that consumption of a multiple-micronutrient
      fortified beverage for 16 weeks had significant effects on iron status, iodine
      status, physical fitness, and cognitive performance among iron- and/or iodine
      deficient Filipino schoolchildren. Anthelmintic therapy improved iron status of
      anemic children and iodine status of the iron-adequate children at baseline but
      it had no effect on physical fitness and cognitive performance. The results from
      the clinical study showed that a multiple-micronutrient-fortified beverage could
      play an important role in preventing and controlling micronutrient deficiencies.

PMID- 17016956
TI  - Drinking to their health: social analysis of a micronutrient-fortified beverage
      field trial.
AB  - Anthropologic research was conducted among pregnant and lactating women in rural
      Tanzania in conjunction with clinical trials of a micronutrient-fortified
      beverage. Use of the beverage was examined through interviews and ethnographic
      observation in clinics and at home. Women liked the taste of the beverage,
      considered it beneficial to their health, preferred it to pills or injections,
      and most were willing and able to use it according to instructions. Most consumed
      the beverage according to schedule in the hope of improving pregnancy outcomes.
      However, public health facilities in Tanzania are not currently equipped to
      ensure regular delivery of micronutrient supplements, and many of the women with
      the worst nutrition profiles are also those who would be least able to purchase
      supplements on the open market. Successful distribution of micronutrient
      supplements in forms that appeal to consumers, such as a fortified beverage, will
      require programmatic attention to locally appropriate social marketing and to the
      challenges of reaching those with extremely low incomes.

PMID- 17016957
TI  - Communicating the benefits of micronutrient fortification.
AB  - Food fortification offers an affordable, convenient, and effective mechanism to
      improve the nutrition status of large segments of a population. However, the
      success of fortification has been less than public-health professionals and
      private-sector companies alike have hoped for, though often for different
      reasons. As new opportunities are available, success will be dictated by the
      ability of public health professionals to learn from private food companies'
      marketing efforts and, in turn, for the food companies to learn from the public
      health sector about how to reach groups who need fortified products the most.
      Simply having fortified products on the market does not promise that consumers
      will use the products or that businesses will continue to promote them. Carefully
      crafted and strategically implemented behavior-change communication can inform
      and motivate consumers to purchase and use the products appropriately, and, in
      turn, can motivate food companies, program managers, and policy makers to
      participate in the marketing of these products. Public health and development
      professionals can learn from the success of private-sector companies in creating
      demand for products. Good consumer research and testing can guide effective
      development and marketing of fortified products, as they do for all products and
      services. Private-sector companies that know how to market products need
      assistance to focus on the poorest segments of a population to pursue cost
      effective strategies to get the product to those in need, in addition to those
      with purchasing power for the new product. Audience-specific marketing strategies
      can ensure that the same fortified product reaches every person who would benefit
      from it.

PMID- 17016958
TI  - Role of public-private partnership in micronutrient food fortification.
AB  - Iron, iodine, and vitamin A deficiencies prevent 30% of the world's population
      from reaching full physical and mental potential. Fortification of commonly eaten
      foods with micronutrients offers a cost-effective solution that can reach large
      populations. Effective and sustainable fortification will be possible only if the
      public sector (which has the mandate and responsibility to improve the health of
      the population), the private sector (which has experience and expertise in food
      production and marketing), and the social sector (which has grass-roots contact
      with the consumer) collaborate to develop, produce, and promote micronutrient
      fortified foods. Food fortification efforts must be integrated within the context
      of a country's public health and nutrition situation as part of an overall
      micronutrient strategy that utilizes other interventions as well. Identifying a
      set of priority actions and initiating a continuous dialogue between the various
      sectors to catalyze the implementation of schemes that will permanently eliminate
      micronutrient malnutrition are urgently needed. The partners of such a national
      alliance must collaborate closely on specific issues relating to the production,
      promotion, distribution, and consumption of fortified foods. Such collaboration
      could benefit all sectors: National governments could reap national health,
      economic, and political benefits; food companies could gain a competitive
      advantage in an expanding consumer marketplace; the scientific, development, and
      donor communities could make an impact by achieving global goals for eliminating
      micronutrient malnutrition; and by demanding fortified foods, consumers empower
      themselves to achieve their full social and economic potential.

PMID- 17016959
TI  - Public-private sector alliances for food fortification: time for optimism.

PMID- 17016961
TI  - An overhaul of the current pediatric residency training in Taiwan.

PMID- 17016960
TI  - Keynote speech: micronutrient malnutrition.

PMID- 17016962
TI  - Challenges of pediatric residency training in Taiwan.
AB  - A crisis in pediatric residency training today has raised serious concerns about
      the healthcare quality for children in Taiwan. The purpose of this study was to
      document the problems and to propose possible solutions for improvement. The
      problems include: 1) manpower shortage due to the difficulty of recruiting
      pediatric residents; 2) heavy workload that hinders learning; 3) lack of
      assessment and poor program planning; and 4) inadequate institutional and
      financial support. As a result, physicians' competencies are not guaranteed at
      the end of residency training, even with the pediatric board certification.
      Possible solutions may include: 1) conducting research on physician manpower
      statistics, work hours and environment; 2) establishing a Residency Program
      Review Committee and provision of standards for accreditation; 3) defining the
      competencies mandated as a general pediatrician and developing a set of
      measurable qualitative standards; 4) encouraging new programs with flexibility
      (e.g., primary care); and 5) pursuing adequate institutional and financial
      supports.

PMID- 17016963
TI  - Safety monitoring in vaccine development and immunization.
AB  - The development of vaccines has been one of the most important achievement in
      preventive medicine. As the incidence of vaccine-preventable diseases is reduced
      by immunization, general public becomes increasingly concerned about the safety
      associated with vaccine. Vaccine safety is extensively evaluated through animal
      safety studies, clinical trials, during manufacturing processes, and
      postlicensure surveillance. Safety monitoring in postlicensure surveillance has
      relied on passive reporting system and epidemiological studies, including Vaccine
      Adverse Event Reporting System (VARES), Vaccine Safety Datalink (VSD) Project and
      others. Approximately 10,000 reports per year are submitted to VAERS. About 15%
      of these describe serious events and 85% of reports are classified as not-serious
      events. The system analyzed frequently reported adverse reactions, rare events,
      intussusception after rotavirus vaccine, cases of sudden infant death syndrome
      (SIDS), and safety of various vaccines. The evidence for a causal relationship
      with vaccines can be classified into five categories: no evidence, evidence was
      inadequate to accept or reject, evidence favors rejection, evidence favors a
      causal relationship, and evidence established. Future challenges involve
      improving survey and monitoring system of adverse events after immunization,
      enhancing vaccine safety research and vaccine risk communication, and possibility
      of increased reactogenicity in new and combined vaccines.

PMID- 17016964
TI  - Rubella seroprevalence among young women taipei county after routine measles,
      mumps and rubella immunization program.
AB  - To better target rubella immunization efforts by determining the age-specific
      rubella seroprevalence and the related factors for children in Taiwan after the
      1986 national vaccine policy. A cross-sectional study was conducted for these
      girls aged 10 years (1994 cohorts), 13 years (1991 cohorts), 16 years (1988
      cohorts), and 19 to approximately 22 years (1982-1985 cohorts), respectively, in
      2004 in Taipei county. Participants were given a questionnaire detailing family
      income, education level, ethnicity of mother, number of siblings, and history of
      rubella infection. Possible predictors of rubella seropositivity and differences
      in seroprevalence were calculated by multivariate logistic regression analysis. A
      total of 826 cases were recruited. The geometric mean titer of rubella IgG
      antibody was 60.7 +/- 2.1 IU/ml. Rubella seropositive rates were 282/287 (98.3%)
      in children aged 10 years, 234/235 (99.6%) in aged 13 years, 179/185 (96.8%) in
      aged 16 years, and 110/119 (92. 4%) in aged 19-22 years. Older age, low maternal
      education level, and foreign mothers were correlated with seronegativity (p <
      0.05). The MMR vaccine program has induced effectively the immunity against
      rubella. However, to eliminate congenital rubella syndrome, more effort should be
      taken for the vaccination of susceptible adolescents and young women.

PMID- 17016965
TI  - Gastric volvulus in children.
AB  - Gastric volvulus (GV) is a rare disease in children that may not be recognized
      early in its course. We retrospectively analyzed 15 patients under 18 years of
      age who presented to our medical center with GV between January 1995 and June
      2005. Patients with complete volvulus and acute obstruction requiring immediate
      intervention were defined as acute GV. Chronic GV was diagnosed in the presence
      of partial volvulus with chronic, nonspecific symptoms and signs. Chronic GV (12/
      15) was more common than acute GV (3/15). Organoaxial GV was the most common type
      (9/15), and there was a high incidence (6/15) of associated anomalies that
      predisposed to the condition. None of our patients had Borchardt's triad (acute
      localized epigastric distension, unproductive retching, and the inability to pass
      a nasogastric tube) which is described in adults with acute GV. Acute GV was
      immediately treated surgically, but conservative management was successful in
      patients with chronic idiopathic GV. When acute GV in children fails to exhibit
      the full gamut of Borchardt's triad, the diagnosis may be delayed. Immediate
      surgical reduction is recommended for acute GV. For chronic idiopathic GV, the
      treatment may be based on the age at diagnosis, the severity of symptoms, and how
      patients are expected to comply with conservative measures.

PMID- 17016966
TI  - Nationwide singleton birth weight percentiles by gestational age in Taiwan, 1998
      2002.
AB  - There are limited nationwide population-based data about birth weight percentiles
      by gestational age in Taiwan. The purpose of this study was to develop updated
      intrauterine growth charts that are population based and contain the information
      of birth weight percentiles by gestational age for singleton newborns in Taiwan.
      We abstracted and analyzed the birth registration database from the Ministry of
      the Interior in Taiwan during the period of 1998-2002 that consisted of over one
      million singleton births. Percentiles of birth weight for each increment of
      gestational week from 21 to 44 weeks were estimated using smoothed means and
      standard deviations. The analyses revealed that birth weight rose with advancing
      gestational age, with greater slopes during the third trimester and then leveled
      off beyond 40 weeks of gestational age. The male to female ratio ranged from
      1.088 to 1.096. The mean birth weights during the period of 1998-2002 were higher
      than those previously reported for the period of 1945-1967; while the birth
      weight distribution and percentile during the period of 1998-2002 were similar to
      those reported for the period of 1979-1989. The 10th, 50th, and 90th percentiles
      of birth weigh at 40th gestational age among the male newborns were 2914, 3374,
      and 3890 g respectively; and for the female newborns 2816, 3250, and 3747 g. At
      the gestational age of 37 weeks, the 10th, 50th, and 90th percentiles of birth
      weigh among the male newborns were 2499, 2941, and 3433 g respectively; and for
      the female newborns 2391, 2832, and 3334 g. From 1998 to 2002, there was a
      gradual increase in the prevalence of low birth weight and preterm birth together
      with the percentage of infants born to foreign-born mothers. This study provides
      the first nationwide singleton intrauterine growth charts in Taiwan that are
      population-based and gender-specific. The normative data are particularly useful
      for the investigation of predictors and outcomes of altered fetal growth.

PMID- 17016967
TI  - Vein of Galen aneurysm complicated with pulmonary hypertension: report of one
      newborn case.
AB  - The vein of Galen aneurysm is a rarely seen congenital intracranial vascular
      malformation with abnormal aneurysmal dilation of the vein of Galen in neonatal
      stage. We report a full- term female newborn presented with intractable heart
      failure, pulmonary artery hypertension, and respiratory distress soon after
      birth, in whom persistent pulmonary hypertension of newborn was suspected
      initially. Further study by ultrasound revealed turbulent blood flow in the
      cerebral vascular lesion in the region of vein of Galen; therefore, secondary
      pulmonary artery hypertension complicated with 'steal' phenomenon was impressed.
      With the advancement of diagnostic technique, ultrasound provides a rapid and
      noninvasive method for diagnosing the condition.

PMID- 17016968
TI  - Congenital dacryocystocele with acute dacryocystitis: report of two cases.
AB  - Congenital dacryocystocele is an uncommon lesion of the nasolacrimal drainage
      system of newborns. The lesion often develops secondary infection due to the
      obstruction of both distal and proximal nasolacrimal ducts. Early recognition by
      experienced pediatrician might initiate effective therapy to prevent the
      progression to possible secondary infection. However, there is no standard
      criteria for optimal treatment. Hence, we review the literature and report two
      newborns with congenital dacryocystocele in one of which progressed to secondary
      infection, dacryocystitis.

PMID- 17016969
TI  - Childhood vulvovaginitis: report of two cases.
AB  - Vaginal discharge in young prepubertal girls is a common problem in clinical
      practice. No specific infective pathogen is identified in most of the children.
      The reported common microbes include group A beta-hemolytic streptococci,
      Haemophilus influenzae and some Gram-negative bacilli. Sexually transmitted
      pathogens such as Neisseria gonorrhoeae and Chlamydia trachomatis are important
      causes of vulvovaginitis in children suffering from sexual abuse. We report two
      cases of prepubertal vulvovaginitis presenting with profuse purulent vaginal
      discharge, and H. influenzae and N. gonorrhoeae identified respectively. Both
      girls denied any sexual exposure and there was no evidence of sexual abuse. They
      responded well to antibiotic treatment, and no symptoms recurred in the following
      months. We would like to emphasize the defined etiology of childhood
      vulvovaginitis and appropriate treatment, in addition to gynecological evaluation
      for evidence of sexual abuse.

PMID- 17016970
TI  - [Sensitivity in diathesis and affective psychoses. 1927].

PMID- 17016971
TI  - [Traumatic stupor, ether administration and recovery: their contribution to the
      psychopathology of stupor. 1927].

PMID- 17016972
TI  - [Emotional psychopathic disorders in the phenomena of mental automatism. 1927].

PMID- 17016973
TI  - [Report of three cases of recovery from delirium without predisposing paranoia
      states. 1927].

PMID- 17016974
TI  - [Motivated delirium eating. 1928].

PMID- 17016975
TI  - [The crisis of catalepsy. Its diagnosis with pathological sleep. Their connection
      with hysteria and catatonia. 1928].

PMID- 17016976
TI  - [The idea of being ugly. 1928].

PMID- 17016977
TI  - [Pick's disease (circumscribed senile atrophy). 1928].

PMID- 17016978
TI  - [Mindedness. 1929].

PMID- 17016979
TI  - [V. General paralysis with the mental automatism syndrome. 1929].

PMID- 17016980
TI  - [Schizo-mania in its imaginative form. 1930].

PMID- 17016981
TI  - Training faces biggest shake-up since project 2000.

PMID- 17016982
TI  - Stay in touch.
AB  - Touch is used in many cultures as a means of relating directly with another
      person. In this seventh article in our Heart of Nursing series, we look at how
      touch, used judiciously, can be a priceless form of doing.

PMID- 17016983
TI  - Sharing the care.
AB  - The expansion of healthcare support workers' roles has created tensions and
      opportunities for all staff. Key issues include delegation and accountability,
      education, regulation and pay.

PMID- 17016984
TI  - Papering over the cracks.

PMID- 17016985
TI  - Improving the fundamental aspects of patient care.
AB  - The Welsh Assembly Government published the document Fundamentals of Care (2003)
      to support measures for quality improvement of care in Wales. This article
      reports on the progress being made in raising awareness of this framework and
      improving the quality of patient care in one large integrated NHS trust. The
      trust's steering group was instrumental in putting the guidance into action,
      which resulted in project development and improved practice.

PMID- 17016986
TI  - Understanding the research process in nursing.
AB  - This article provides an overview of the research process in nursing, outlining a
      logical and structured approach to answering research questions. Illustrations
      from a hypothetical research study are used to outline procedures that are
      relevant to NHS research.

PMID- 17016987
TI  - The nursing role in preventing delay in patient discharge.
AB  - This article uses a case scenario of a delayed patient discharge to explore
      multidisciplinary discharge planning. The common causes of delayed discharge are
      described and the importance of effective multidisciplinary team-working is
      emphasised through a review of a 'whole systems approach' to discharge. The role
      of the nurse in discharge planning is examined, as are the effects of poor
      interprofessional communication and documentation, and their link to hospital
      readmission. Issues of patient power, choice, participation and control are
      emphasised. The value of good information-giving is highlighted, both for the
      patient and the patient's carers.

PMID- 17016988
TI  - Tissue donation: benefits, legal issues and the nurse's role.
AB  - This article provides an overview of tissue donation. It examines the importance
      of the nurse's role in relation to tissue donation and caring for bereaved
      relatives. The provisions of the Human Tissue Act 2004, which came into force in
      September 2006, are also outlined.

PMID- 17016989
TI  - Nasogastric feeding.

PMID- 17016990
TI  - Humbling experience.

PMID- 17016991
TI  - Lead by example.

PMID- 17016992
TI  - Staffing levels and a 65:35 skill mix.

PMID- 17016993
TI  - Bound to care.
AB  - Healthcare practitioners must be better educated in the legal and ethical
      principles underpinning the delivery of health care.

PMID- 17016995
TI  - Who has the time for break?

PMID- 17016994
TI  - Love me tender.
AB  - Sympathy, empathy and loving concern transform lives. But to be able to care for
      people in this way means nurses' hearts must be open and healed.

PMID- 17016996
TI  - Using structured reflection on a critical incident to develop a professional
      portfolio.
AB  - This article demonstrates reflective practice by examining a critical incident
      that took place at a children's burns unit. The development of reflective skills
      is documented using a method of structured reflection. The concepts of
      aesthetics, personal knowing, empirics and ethics are considered to reflect on
      the critical incident. Reflection is considered in the context of developing a
      portfolio to analyse and demonstrate learning in practice.

PMID- 17016997
TI  - Advance statements: legal and ethical implications.
AB  - This article informs nurses of the background and purpose of advance statements
      (advance directives or living wills), and discusses the legal and ethical issues
      associated with their use.

PMID- 17016998
TI  - Primary percutaneous coronary intervention in patients with acute myocardial
      infarction.
AB  - This article examines the development of primary percutaneous coronary
      intervention (PPCI) for the treatment of acute ST-segment elevation myocardial
      infarction in the UK. It discusses the evidence related to PPCI, the
      technological advances to improve accessibility to this treatment and the nursing
      care of a patient undergoing this procedure.

PMID- 17016999
TI  - Acute wound closure.

PMID- 17017000
TI  - No problem too small.

PMID- 17017001
TI  - Of pharoahs and sphinxes.

PMID- 17017002
TI  - Stand out from the crowd.

PMID- 17017003
TI  - Toward an evidence-based toxicology.
AB  - The increasing demands on toxicology of large-scale risk assessment programmes
      for chemicals and emerging or expanding areas of chemical use suggest it is
      timely to review the toxicological toolbox. Like in clinical medicine, where an
      evidence-based medicine (EBM) is critically reviewing traditional approaches,
      toxicology has the opportunity to reshape and enlarge its methodology and
      approaches on the basis of compounded scientific knowledge. Such revision would
      have to be based on structured reviews of current practice, ie, assessment of
      test performance characteristics, mechanistic understanding, extended quality
      assurance, formal validation and the use of integrated testing strategies. This
      form of revision could optimize the balance between safety, costs and animal
      welfare, explicitly stating and, where possible, quantifying uncertainties. After
      a self-critical reassessment of current practices and evaluation of the thus
      generated information, such an evidence-based toxicology (EBT) promises to make
      better use of resources and to increase the quality of results, facilitating
      their interpretation. It shall open up hazard and also risk assessments to new
      technologies, flexibly accommodating current and future mechanistic
      understanding. An EBT will be better prepared to answer the continuously growing
      safety demands of modern societies.

PMID- 17017004
TI  - Lower expression of p14ARF and p16INK4a correlates with higher DNMT3B expression
      in human oesophageal squamous cell carcinomas.
AB  - Oesophageal squamous cell carcinoma (ESCC) is one of the most common malignancies
      and is the sixth cause of cancer-related death in the world. Inactivation of cell
      cycle regulating genes, such as p14ARF and p16INK4a, and cell adhesion genes,
      such as E-cadherin, is common in cancer, and results from genetic and/or
      epigenetic alterations. Therefore, we have analysed the mRNA expression of
      p14ARF, p16INK4a and E-cadherin in 17 matched ESCC and normal mucosal samples
      obtained from Brazilian patients by semi-quantitative RT-PCR. The expression of
      p14ARF and p16INK4a was absent or reduced in several ESCC samples.
      Hypermethylation of CpG islands, caused by the action of DNA methyltransferases
      (DNMTs), is a major form of epigenetic inactivation of the p14ARF and p16INK4a
      genes in tumours. Hence, we also investigated the mRNA expression of the human
      DNA methyltransferases in normal oesophageal mucosa and in the tumour matched
      samples. All DNMTs were constitutively expressed in the normal oesophageal mucosa
      but a significantly higher expression of DNMT3B was observed in the tumours. Data
      analysis by the Spearman rank test showed that the expression of DNMT3B was
      inversely correlated with that of p14ARF and p16INK4a. Our results suggest that
      DNMT3B over-expression may be involved in the suppression or lower expression of
      p14ARF and p16INK4a observed in ESCC.

PMID- 17017005
TI  - Effect of gallic acid on renal biochemical alterations in male Wistar rats
      induced by ferric nitriloacetic acid.
AB  - The present study is an effort to identify a potent chemopreventive agent against
      various diseases (including cancer) in which oxidative stress and cell
      proliferation plays an important causative role. This study was designed to
      investigate the effect of gallic acid against ferric nitrilotriacetic acid (Fe
      NTA)-induced carcinogen/ drug metabolizing phase I and phase II enzymes,
      antioxidative parameters, kidney markers, tumour promotion markers and lipid
      peroxidation (LPO) in kidney of male Wistar rats. Fe-NTA (9 mg Fe/kg body weight,
      intraperitoneally) caused significant depletion in the detoxification and
      antioxidant enzyme armoury with concomitant elevation in renal LPO, serum
      creatinine, blood urea nitrogen, hydrogen peroxide generation, ornithine
      decarboxylase activity and [3H]thymidine incorporation into renal DNA. However,
      pretreatment of animals with gallic acid (10 and 20 mg/kg body weight) resulted
      in a significant decrease in the levels of the parameters measured (P <0.001).
      Renal glutathione content (P <0.001), glutathione metabolizing enzyme (P <0.001)
      and antioxidant enzyme levels were also recovered to a significant level (P
      <0.001). The enhanced reduced glutathione level and enzyme activities involved in
      xenobiotic metabolism and maintaining antioxidant status of cells are suggestive
      of a chemopreventive efficacy of gallic acid against Fe-NTA-mediated oxidative
      stress, toxicity and cell proliferative response in Wistar rats.

PMID- 17017006
TI  - Dietary di(2-ethylhexyl)phthalate-impaired glucose metabolism in experimental
      animals.
AB  - The effects of chronic intake of di(2-ethylhexyl)phthalate (DEHP) on the main
      intermediate glycolytic metabolites in liver and gastrocnemius muscle were
      investigated in experimental animals. Male Wistar rats (90-100 g) were fed for 21
      days either with a standard chow or the same diet supplemented with 2% (w/w) of
      DEHP. The DEHP-fed rats had an altered in vivo glucose tolerance associated with
      abnormal glucose intermediate metabolite contents in liver and skeletal muscle.
      In these rats, the hepatic content of glucose-6-phosphate (G-6-P), fructose-6
      phosphate, pyruvate, lactate, glucose-1-phosphate and glycogen decreased. At the
      same time, the G-6-P content decreased while the pyruvate and lactate levels
      increased in skeletal muscle. These data, along with the high plasma glucose
      concentration and the normal lactate blood levels of this group, could indicate
      that DEHP-fed rats could present a deficiency in muscle glucose and lactate
      transport, a reduction of the flux through muscle hexokinase and hepatic
      glucokinase, and a reduction in glycogen synth-

PMID- 17017007
TI  - Chromatin remodelling and chromosome damage distribution.
AB  - Histone acetylation/deacetylation constitute the most relevant chromatin
      remodelling mechanism to control DNA access to nuclear machinery as well as to
      mutagenic agents. Thus, these epigenetics mechanisms could be involved in
      processing DNA lesions into chromosomal aberrations. Although radiation-induced
      DNA lesions are believed to occur randomly, in most cases chromosome breakpoints
      appear distributed in a non-random manner. In order to study the distribution of
      chromosome damage induced by clastogenic agents in relation to chromosome histone
      acetylation patterns, an experimental model based on treating Chinese hamster
      cells with endonucleases and ionizing radiations as well as immunolabelling
      metaphase chromosomes with antibodies to acetylated histone H4 was developed. The
      analysis of intra- and interchromosome breakpoint distribution has been carried
      out on G-banded chromosomes, and results obtained were correlated with chromosome
      acetylated histone H4 profiles. A co-localization of intrachromosomal breakpoints
      induced by Alu I, Barn HI and DNase I as well as by neutrons and gamma-rays was
      observed. Radiation- and endonuclease-induced breakpoints tend to cluster in less
      condensed chromosome regions (G-light bands) that show the highest levels of
      acetylated histone H4. The analysis of interchromosomal distribution of radiation
      induced lesions showed a concentration ofbreakpoints in Chinese hamster
      chromosomes with particular histone acetylation patterns. The fact that
      chromosome break-points occur more frequently in transcriptionally competent
      chromosome regions suggests that chromatin conformation and nuclear architecture
      could play a role in the distribution of chromosome lesions.

PMID- 17017008
TI  - Delta-aminolevulinic acid dehydratase inhibition and oxidative stress in relation
      to blood lead among urban adolescents.
AB  - To explore lead-induced oxidative stress among urban adolescents, the present
      study, the first from India, was designed to determine the proportion of urban
      adolescents with blood lead >10 microg/dL and its impact on selected oxidative
      stress parameters and delta-aminolevulinic acid dehydratase (delta-ALAD)
      inhibition, which could be used as biomarkers of lead intoxication. A total of
      39, urban, male adolescents, drawn from Lucknow and adjoining areas, were
      recruited to determine lead, delta-ALAD, malondialdehyde (MDA) and glutathione
      (GSH) in blood and catalase (CAT) in RBCs. Mean level of blood lead was 9.96 +/-
      3.63 microg/dL (4.62-18.64); 43% of adolescents crossed the Centre for Disease
      Control (CDC) intervention level of 10 pg/dL blood lead. On the basis of blood
      lead levels (BLLs), adolescents were categorized into two groups: Group I and
      Group II had a blood lead <10 microg/dL (7.40 +/- 1.62) and >10 microg/dL (13.27
      +/- 2.67), respectively, with significantly different mean values (P <0.001).
      Age, sex, body mass index (BMI), Hb level (malnutrition), and area of living as
      confounders of lead exposure and toxicity were not statistically different
      between the two groups. However, delta-ALAD activity was significantly lower (P
      <0.001), while CAT activity was higher in Group II than in Group I (P <0.01). MDA
      level was also significantly higher in Group II compared to Group I (P <0.001).
      There were significant negative correlation of BLL with 6-ALAD (r= -0.592, P
      <0.001), and positive correlations with CAT (r=0.485, P <0.01) and MDA (r=0.717,
      P <0.001). Interestingly, delta-ALAD, in turn, had significant negative
      correlations with CAT (r= -0.456, P <0.01) and MDA (r= -0.507, P <0.01). Results
      of the present pilot study provide clues to the possible low level of lead
      induced oxidative stress in urban adolescents, suggesting that lead-induced 6
      ALAD inhibition can also be an indicator of oxidative stress. The potential of
      oxidative stress parameters to be used as biomarkers of lead toxicity warranted
      further investigation.

PMID- 17017009
TI  - HPLC determination of ciprofloxacin, cloxacillin, and ibuprofen drugs in human
      urine samples.
AB  - This paper reports, for the first time, a liquid chromatographic method for the
      simultaneous determination of three frequently co-administered active principles,
      two antibiotics, ciprofloxacin (CIPRO) and cloxacillin (CLOXA) belonging to the
      fluoroquinolones and beta-lactam families, respectively, and ibuprofen (IBU), a
      non-steroidal anti-inflammatory drug. The chromatographic separation was
      performed on a C-18 analytical column, using isocratic elution with methanol
      acetonitrile-pH 3 formate buffer (CT = 0.1 M) (15:12:73, v/v/v) for 3 min and,
      after that, a linear gradient with methanol-acetonitrile (88:12, v/v) for 8 min.
      Several absorption spectra were obtained for each peak using a DAD detector.
      Chromatograms at the maximum absorption wavelength for each analyte, 220 nm for
      both IBU and CLOXA, and 280 nm for CIPRO were selected as the most suitable. The
      proposed chromatographic method requires about 15 min per sample. The presence of
      a urine background was tested and no interference was found. The method was
      satisfactorily applied to the determination of CIPRO, CLOXA, and IBU, in
      fortified urine, and in urine samples from a patient undergoing treatment with
      these three active principles, among others. Limits of quantification in urine
      were 1.00, 1.70, and 2.87 microg/mL for CIPRO, CLOXA, and IBU, respectively.

PMID- 17017010
TI  - New approach to large-volume injection in reversed-phase high performance liquid
      chromatography: determination of atrazine and hydroxyatrazine in soil samples.
AB  - A well established method of direct injection of larger than conventional sample
      volumes ranging from 0.1 mL to 10 mL in HPLC is the injection valve method in
      which a loop of tubing is totally or partially filled with sample. Recent HPLC
      pumps have a flow-rate setting accuracy of +/- 1-2% over a flow-rate range from
      0.1 mL/min to 10 mL/min and the flow stability is 0.2% or less. Quarternary low
      pressure gradient pumps are widely available and used, but all their hydraulic
      lines are seldom utilised. The idea of using one line of a common commercial HPLC
      quaternary low-pressure pump for direct on-column injection (pumping) of large
      sample volumes ranging from 1 mL to 100 mL was tested. This approach was
      evaluated during practical work on the development of an RP-HPLC method of
      determination of residual atrazine and hydroxyatrazine. In lysimetric
      environmental experiments hydroxyatrazine was formed in situ in a soil column by
      hydrolysis of atrazine. The results proved the applicability of this approach not
      only in experiments with model mixtures of analytes at microg/L levels in
      solutions. Analysis of 20 mL of soil leachates and extracts of soil samples
      containing atrazine and hydroxyatrazine at the 10 microg/kg level (in dry soil)
      revealed that good figures-of-merit were preserved, even in the presence of a
      large excess of humic substances.

PMID- 17017011
TI  - High-performance liquid chromatographic enantioseparations on capillary columns
      containing crosslinked polysaccharide phenylcarbamate derivatives attached to
      monolithic silica.
AB  - Monolithic capillary columns containing native silica gel were covalently
      modified with 3,5-disubstituted phenylcarbamate derivatives of cellulose and
      amylose and applied for enantioseparations in capillary LC. The method previously
      used for covalent immobilization of polysaccharide phenylcarbamate derivatives
      onto the surface of microparticulate silica gel was successfully adapted for in
      situ modification of monolithic fused-silica capillary columns. The effects of
      the nature of polysaccharide and the substituents, as well as of multiple
      covalent immobilization of polysaccharide derivative on chromatographic
      performance of capillary columns were studied. The capillary columns obtained
      using this technique are stable in all solvents commonly used in LC and exhibit
      promising enantiomer resolving ability.

PMID- 17017012
TI  - A fast method for determining low-molecular-mass aliphatic carboxylic acids by
      high-performance liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry.
AB  - A fast quantitative high-performance liquid chromatographic separation method
      with atmospheric pressure chemical ionization mass spectrometric detection (HPLC
      APCI-MS) was developed for the determination of low-molecular-mass aliphatic mono
      and dicarboxylic acids typically present in different industrial process waters.
      A mixture of glycolic, lactic, a-glucoisosaccharinic, oxalic, maleic, fumaric,
      succinic, malic, glutaric, methylsuccinic, and adipic acids was separated using
      an RP chromatographic system. Adipic acid was used as an internal standard to
      calculate correlation coefficients for the acids studied. The chromatographic
      analysis of these acids was primarily carried out by means of gradient elution
      with an aqueous formic acid solution (0.15%, pH 2.5) and methanol using a
      modified C18 stationary phase. Good acid separation could be obtained for all
      acids by optimizing the chromatographic conditions. The method provides a simple
      sample preparation and faster analysis time compared to the traditional gas
      chromatographic methods, thus enabling almost real-time monitoring of these
      acids. Finally, the method developed was applied to the analysis of a complex
      mixture of aliphatic hydroxy carboxylic acids, which are formed as alkaline
      degradation products of carbohydrates during wood delignification and are present
      in the cooking spent liquor (black liquor).

PMID- 17017013
TI  - Comparative enantioseparation of seven triazole fungicides on (S,S)-Whelk O1 and
      four different cellulose derivative columns.
AB  - The comparative enantioseparation of seven chiral triazole fungicides on a Pirkle
      type (S,S)-Whelk O1 chiral column and four different cellulose derivative
      columns, namely cellulose tribenzoate (CTB), cellulose tris(4-methylbenzoate)
      (CTMB), cellulose triphenylcarbamate (CTPC), and cellulose tris(3,5
      dimethylphenyl carbamate) (CDMPC), in normal phase mode is described. The seven
      triazole fungicides investigated were tebuconazole, hexaconazole, myclobutanil,
      diniconazole, uniconazole, paclobutrazol, and triadimenol. The chiral separation
      of each solute was investigated with ethanol, n-propanol, iso-propanol, and n
      butanol, respectively, as polar modifier in the hexane mobile phase. The results
      revealed that (S,S)-Whelk O1 was less than universal and only hexaconazole and
      triadimenol underwent enantioseparation. Among the self-prepared cellulose
      derivative columns used, the enantiomeric resolution capacities for the studied
      analytes generally decreased in the order CDMPC > CTPC > CTMB > CTB. The best
      enantioseparation of the analytes was mostly obtained on CDMPC and none of them
      were enantioseparated on CTB. The chiral recognition mechanisms between the
      analytes and the chiral selectors are discussed.

PMID- 17017014
TI  - Simultaneous analysis of seven astragalosides in Radix Astragali and related
      preparations by liquid chromatography coupled with electrospray ionization time
      of-flight mass spectrometry.
AB  - A method has been developed for the qualitative and quantitative analysis of
      pharmacologically active astragalosides isolated from several species of the
      genus Astragalus by high performance liquid chromatography coupled with
      electrospray ionization time-of-flight mass spectrometry. Seven astragalosides in
      Radix Astragali and their commercial pharmaceutical preparations were analyzed
      using the developed method. The extracted ion current chromatograms were obtained
      from the total ion current chromatogram using the m/z of [M+Na]+ ions produced by
      target compounds for peak determination. The limits of detection and limits of
      quantification were in the range of 0.10-0.22 ng and 0.22-0.52 ng in full scan
      mode, respectively. All calibration curves showed good linear regression (r2 > or
      = 0.9965) within the test range. The overall intra- and inter-day precision was
      less than 2.86% for peak area and the accuracy was higher than 92.9% on using
      ginsenoside I as internal standard. The assay was successfully utilized to
      analyze the major biologically active astragalosides in six samples of Astragalus
      membranaceus (Fisch.) Bge var. mongholicus (Bge.) Hsiao. and eight commercial
      preparations. The overall results demonstrate that this method is simple,
      selective, and suitable for the quality control of Chinese medicine and their
      preparation in the low nanogram range.

PMID- 17017015
TI  - Capillary electrochromatography with monolithic silica columns. V. Study of the
      electrochromatographic behaviors of polar compounds on monolithic silica having
      surface bound cyano functionalities.
AB  - In this report, a novel polar monolithic capillary column is described for normal
      phase CEC (NP-CEC) of representative polar compounds including mono- and
      oligosaccharides, peptides, and basic drugs. The polar monolithic column, which
      was described in detail in the preceding paper, consisted of silica-based
      monolith bonded with 1H-imidazole-4,5-dicarbonitrile (IDCN) and is denoted as 2CN
      OH-Monolith. Various retention parameters for neutral polar solutes (e.g., mono-
      and oligosaccharides) and charged polar solutes (e.g., peptides and basic drugs)
      were evaluated over a wide-range of elution conditions. These retention
      parameters yielded quantitative assessment for the polar interactions between the
      model solutes and the stationary phase under investigation as well as the effect
      of electromigration of charged solutes on their overall migration in NP-CEC.
      Furthermore, this investigation demonstrated that despite the possibility of
      achieving isocratic separation in NP-CEC for widely differing polar species,
      multistep-gradient elution in NP-CEC is preferred to bring about the rapid
      separation of a large number of polar species in a single run.

PMID- 17017016
TI  - Capillary electrochromatography with monolithic silica columns. IV.
      Electrochromatographic characterization of polar bonded monolithic stationary
      phases having surface-bound cyano functionalities.
AB  - Two polar ligands, namely 3-hydroxypropionitrile and 1H-imidazole-4,5
      dicarbonitrile (IDCN) were covalently attached to epoxy-activated silica-based
      monolithic capillary columns via an epoxide ring-opening reaction to yield CN-OH
      Monolith and 2CN-OH-Monolith, respectively. The silica monolith was prepared by a
      sol-gel process, and the resulting "rod-like" stationary phase was subjected to
      pore tailoring with an alkaline solution to convert small pore domains to
      mesopore domains, thus yielding a monolith with bimodal pore structure consisting
      of flow through pores (i.e., flow channels for mobile-phase flow) and mesopores
      that provide most of the adsorption capacity of the monolith toward the separated
      solutes. The two polar monoliths, CN-OH-Monolith and 2CN-OH-Monolith, were
      evaluated in normal-phase CEC with organic-rich mobile phases less polar than the
      stationary phase. The 2CN-OH-Monolith bearing more polar functions than the CN-OH
      Monolith exhibited more retention and improved selectivity toward model polar
      solutes.

PMID- 17017017
TI  - Separation of parabens in capillary electrochromatography using poly(styrene
      divinylbenzene-methacrylic acid) monolithic column.
AB  - In this study, a series of poly(styrene-divinylbenzene-methacrylic acid)
      monolithic capillaries was used as the separation column of CEC for the analyses
      of parabens in commercial pharmaceutical and cosmetic products. The results
      showed that the chromatographic characteristics of these analytes were strongly
      affected by the preparation condition of the monolithic column including monomer
      content, porogenic solvent composition, and polymerization time. Baseline
      separations were markedly sped up by lowering the polymerization time without any
      obvious loss of resolution. Furthermore, mobile-phase composition (pH, ACN, and
      electrolyte concentration) was also able to effectively improve the separation
      behavior. Similar to the influence of lowering the polymerization time, retention
      times for all analytes were significantly shortened in the CEC method by
      decreasing the electrolyte concentration in the mobile phase.

PMID- 17017018
TI  - Separation and determination of epinephrine and dopamine in traditional Chinese
      medicines by micellar electrokinetic capillary chromatography with laser induced
      fluorescence detection.
AB  - A micellar electrokinetic capillary chromatography method with laser-induced
      fluorescence detection was developed for the analysis of epinephrine and dopamine
      after derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole. The optimum
      derivatization conditions were: 30 mM sodium borate (pH adjusted to 8.0 with 1.0
      M HCl), reaction time 30 min at 60 degrees C. Baseline separation was achieved
      within 14 min with a running buffer composed of 10 mM sodium borate + 25 mM
      sodium dodecyl sulfate (pH adjusted to 9.5 with 0.1 M NaOH) and an applied
      voltage of 15 kV. Good linearity relationships (correlation coefficients: 0.9991
      for epinephrine and 0.9985 for dopamine) between peak areas and concentrations of
      the analytes were obtained. The detection limits and quantification limits for
      epinephrine and dopamine were 0.0038 mg/L and 0.013 mg/L, and 0.065 mg/L and
      0.020 mg/L, respectively. The method was applied to the analysis of the two
      compounds in two Chinese medicines with recoveries in the range of 92.6-108.7%.

PMID- 17017019
TI  - Method for enantiomeric purity of a quinuclidine candidate drug by capillary
      electrophoresis.
AB  - A chiral procedure based on EKC was developed and validated for determination of
      the enantiomeric purity of PHA-543613, a drug candidate that was under
      development for treatment of the cognitive deficits of Alzheimer's disease and
      schizophrenia. Separation of enantiomers is accomplished via differential,
      enantiospecific complexation with a single-isomer, precisely sulfated beta-CD and
      heptakis-6-sulfato-beta-CD (HpS-beta-CD). Both neutral and sulfated CDs were
      screened before selecting HpS-beta-CD as the chiral selector. The separation is
      conducted in a 61 cm x 50 microm uncoated fused silica capillary with 25 mM HpS
      beta-CD in pH 2.50, 25 mM lithium phosphate as the separation buffer with
      detection at 220 nm. Application of reverse polarity at -30 kV results in an
      elution time of about 12 min for PHA-543613 and 13 min for the undesired S
      enantiomer. Quantification is versus an authentic reference S-enantiomer as an
      external standard in combination with an internal standard. The procedure was
      validated over the range 0.1-2.0% w/w. The detection limit is 0.01-0.02%. The
      amount of distomer intrinsic to the drug substance is about 0.1% or less. The
      developed method was used to generate stability data on multiple lots: in one
      case for up to 3 years.

PMID- 17017020
TI  - Comparison of two capillary electrophoresis online stacking modes by analysis of
      polycyclic aromatic hydrocarbons in airborne particulates.
AB  - Naphthalene, fluorene, pyrene, anthracene, phenanthrene, and chrysene were
      successfully separated by CD-modified MEKC (CD-MEKC) using 20 mM borate (pH 9.0)
      containing 90 mM SDS and 75 mM beta-CD. Two online stacking methods, i.e.,
      sweeping and field-enhanced sample injection (FESI), were explored to enhance the
      detection sensitivity. The influences of some crucial parameters in sweeping and
      FESI procedures were investigated. For FESI method, a plug of water and low
      conductivity sample matrix was used to increase the stacking efficiency. Compared
      with the sweeping method, FESI can increase the sensitivity in the range of 10-20
      fold. The proposed method was used for the analysis of polycyclic aromatic
      hydrocarbons in airborne particulates.

PMID- 17017021
TI  - The effect of the physical matrix on accurate measurements using fixed volume
      analytical techniques.
AB  - In order to perform high accuracy analytical measurements most analytical
      techniques require some form of calibration using standards of the same quantity
      as that being measured. The highest accuracy calibration standards are those
      prepared by mass (gravimetrically) as opposed to by volume (volumetrically). The
      use of gravimetrically prepared standards to calibrate analytical techniques that
      rely on fixed volume injections can cause systematic errors, even when the
      analytical technique does not suffer from a chemical matrix interference. The
      origin of these errors is explained and is demonstrated experimentally for the
      analysis of sulphate in synthetic seawater samples, and the measurement of the
      anionic content of particulate matter following extraction with water and wetting
      agents; where average measurement biases of +2.7 and -3.2%, respectively, were
      observed. Proposals are offered for methods to overcome this 'physical matrix
      effect'.

PMID- 17017022
TI  - Extraction of hydroxyaromatic compounds in river water by liquid-liquid-liquid
      microextraction with automated movement of the acceptor and the donor phase.
AB  - Liquid-liquid-liquid microextraction with automated movement of the acceptor and
      the donor phase technique is described for the extraction of six hydroxyaromatic
      compounds in river water using a disposable and ready to use hollow fiber.
      Separation and quantitative analyses were performed using LC with UV detection at
      254 nm. Analytes were extracted from the acidified sample solution (donor phase)
      into the organic solvent impregnated in the pores of the hollow fiber and then
      back extracted into the alkaline solution (acceptor phase) inside the lumen of
      the hollow fiber. The fiber was held by a conventional 10 microL LC syringe. The
      acceptor phase was sandwitched between the plunger and a small volume of the
      organic solvent (microcap). The acceptor solution was repeatedly moved in and out
      of the hollow fiber using a syringe pump. This movement provides a fresh acceptor
      phase to come in contact with the organic phase and thus enhancing extraction
      kinetics thereby leading to the improvement in enrichment of the analytes. The
      microcap separates the acceptor phase and the donor phase in addition to being
      partially responsible for mass transfer of the analytes from the donor solution
      to the acceptor solution. Under stirring, a fresh donor phase will enter through
      the open end of the fiber that will also contribute to the mass transfer. Various
      parameters affecting the extraction efficiency viz type of organic solvent,
      extraction time, stirring speed, effect of sodium chloride, and concentration of
      donor and acceptor phases were studied. RSD (3.9-5.6%), correlation coefficient
      (0.995-0.997), detection limit (2.0-51.2 ng/mL), enrichment factor (339-630),
      relative recovery (93.2-97.9%), and absolute recovery (33.9-63.0%) have also been
      investigated. The developed method was applied for the analysis of river water.

PMID- 17017023
TI  - Determination of anatoxin-a in environmental water samples by solid-phase
      microextraction and gas chromatography-mass spectrometry.
AB  - In the present work, a method was developed and optimized aiming at the
      determination of anatoxin-a in environmental water samples. The method is based
      on the direct derivatization of the analyte by adding hexylchloroformate in the
      alkalinized sample (pH = 9.0). The derivatized anatoxin-a was extracted by a
      solid-phase microextraction (SPME) procedure, submersing a PDMS fiber in an amber
      vial for 20 min under magnetic stirring. GC-MS was used to identify and quantify
      the analyte in the SIM mode. Norcocaine was used as internal standard. The
      following ions were chosen for SIM analyses (quantification ions in italics):
      anatoxin-a: 191, 164, 293 and norcocaine: 195, 136, 168. The calibration curve
      showed linearity in the range of 2.5-200 ng/mL and the LOD was 2 ng/mL. This
      method of SPME and GC-MS analysis can be readily utilized to monitor anatoxin-a
      for water quality control.

PMID- 17017024
TI  - Response surface methodology in the development of a stacking-sensitive capillary
      electrophoresis method by field-amplified injection for the analysis of tricyclic
      antidepressants in the presence of salts.
AB  - The work presented here explores the possibilities of the electrokinetic
      injection (EK) to achieve sensitive methods for the determination of tricyclic
      antidepressants in biological samples (serum). The addition of ACN to the sample,
      with high content in salts, causes stacking at the tip of the capillary, in a
      similar way as for hydrodynamic injection. An experimental design with the
      response surface methodology has been used to find the optimum composition of the
      matrix of the sample (sodium chloride and ACN percentages) and the conditions for
      the EK (water-plug length, time, and voltage of injection) in few experiments.
      The composition of the separation buffer was the same as utilized in a previous
      paper. The use of a bubble capillary to reach lower detection limits implies a
      loss of the resolution and requires a new optimization. Finally, a comparison
      between electrokinetic and hydrodynamic injections is made.

PMID- 17017025
TI  - Preparation of particle-fixed silica monoliths used in capillary
      electrochromatography.
AB  - Fused-silica capillarieswere packed with porous 1 microm bare silica microspheres
      and immobilized by potassium silicate-formamide in order to obtain columns with
      silica-based monolithic packing. After curing, the particle-fixed monolithic
      columns were octadecylated insitu with dimethyloctadecylchlorosilane. The columns
      were mechanically strong and permeable. No noticeable loss in efficiency was
      found after using a column continuously for 1 month. The performances of the
      particle-fixed silica monolithic columns were evaluated for CEC under RP
      conditions. High separation efficiency (about125 200 plates/m) was obtained by
      using these new types of columns.

PMID- 17017026
TI  - Power ultrasound--a means to promote and control crystallization in
      biotechnology.

PMID- 17017027
TI  - Discovery and applications of small molecule probes for studying biological
      processes.

PMID- 17017028
TI  - Vaginal microbicides for the prevention of HIV transmission.

PMID- 17017029
TI  - Cell adhesion molecules in plants and animals.

PMID- 17017030
TI  - Bone marrow stromal stem cells for repairing the skeleton.

PMID- 17017031
TI  - Polymeric delivery systems for biopharmaceuticals.

PMID- 17017032
TI  - Biotechnological aspects of transport across human skin.

PMID- 17017033
TI  - Inhibitors of amyloid aggregation: technologies for the discovery of novel lead
      compounds.

PMID- 17017034
TI  - Starch retrogradation.

PMID- 17017035
TI  - Re-designing lignin for industry and agriculture.

PMID- 17017036
TI  - Beyond Bayh-Dole and the Lambert Review: an initial product development and
      transaction model for the interface between universities and business.

PMID- 17017037
TI  - The liabilities from regulating gene flow in plant-made pharmaceuticals.

PMID- 17017038
TI  - Safety testing and regulation of genetically engineered foods.

PMID- 17017039
TI  - Design of safe and biologically contained transgenic plants: tools and
      technologies for controlled transgene flow and expression.

PMID- 17017040
TI  - Making oral health fun for little ones.

PMID- 17017041
TI  - The DSM--what exactly is it?

PMID- 17017042
TI  - Schools and suicide.

PMID- 17017043
TI  - Talking about STDs/STIs...today and everyday.

PMID- 17017044
TI  - Comorbidities associated with type 1 diabetes.

PMID- 17017045
TI  - Beverage makers offer schools vending machine options.

PMID- 17017046
TI  - Disaster preparedness in schools for chemical and radiological weapons and agents
      of opportunity.

PMID- 17017047
TI  - 2005 employment decisions under the ADA Title I--survey update.

PMID- 17017048
TI  - New IOM report underscores ongoing threat of med errors.
AB  - Technology may improve the error rate, but careful implementation is absolutely
      critical. Health care provider groups should actively monitor their progress in
      improving medication safety. Medication reconciliation is a worthy goal, but
      implementation is proving more difficult than anticipated.

PMID- 17017049
TI  - 'Condom' catheter can improve outcomes.
AB  - Study undertaken to clear up contradictory results published in previous
      articles. External catheter achieves an 80% reduction in the risk of urinary
      tract infection or death. When there is no negative impact on outcomes, patient
      satisfaction should be the deciding factor.

PMID- 17017050
TI  - Patient safety alert. Hospital reports critical results within one hour.

PMID- 17017051
TI  - AQA, HQA collaborate on national quality strategy.
AB  - Coordinating measurement activities will give patients and providers a better
      look at quality across the entire continuum of care. Organizations say
      collaboration will make quality measurement more accurate and more efficient.
      Newly launched AQA pilot programs will benefit from formation of steering
      committee.

PMID- 17017052
TI  - State task force develops protocols for wristbands.
AB  - Statewide initiative launched in wake of adverse event caused by conflicting
      color codes. New system includes printed information on wristbands, in addition
      to color coding. Several hospitals voluntarily agree to adopt a uniform color
      code for wristbands.

PMID- 17017053
TI  - RFID tags help alert surgeons to problems.
AB  - Estimates say 1,500 objects are left inside patients after surgery each year in
      the United States; two-thirds are sponges. A handheld wand scanning device
      successfully detects sponges in seconds. The author recommends conducting an
      initial count prior to surgical incision, a second count at the beginning of
      wound closure, and a third count before the skin is closed.

PMID- 17017054
TI  - Evolution of genetic architecture under directional selection.
AB  - We investigate the multilinear epistatic model under mutation-limited directional
      selection. We confirm previous results that only directional epistasis, in which
      genes on average reinforce or diminish each other's effects, contribute to the
      initial evolution of mutational effects. Thus, either canalization or
      decanalization can occur under directional selection, depending on whether
      positive or negative epistasis is prevalent. We then focus on the evolution of
      the epistatic coefficients themselves. In the absence of higher-order epistasis,
      positive pairwise epistasis will tend to weaken relative to additive effects,
      while negative pairwise epistasis will tend to become strengthened. Positive
      third-order epistasis will counteract these effects, while negative third-order
      epistasis will reinforce them. More generally, gene interactions of all orders
      have an inherent tendency for negative changes under directional selection, which
      can only be modified by higher-order directional epistasis. We identify three
      types of nonadditive quasi-equilibrium architectures that, although not strictly
      stable, can be maintained for an extended time: (1) nondirectional epistatic
      architectures; (2) canalized architectures with strong epistasis; and (3) near
      additive architectures in which additive effects keep increasing relative to
      epistasis.

PMID- 17017055
TI  - The evolution of genetic architecture under frequency-dependent disruptive
      selection.
AB  - We propose a model to analyze a quantitative trait under frequency-dependent
      disruptive selection. Selection on the trait is a combination of stabilizing
      selection and intraspecific competition, where competition is maximal between
      individuals with equal phenotypes. In addition, there is a density-dependent
      component induced by population regulation. The trait is determined additively by
      a number of biallelic loci, which can have different effects on the trait value.
      In contrast to most previous models, we assume that the allelic effects at the
      loci can evolve due to epistatic interactions with the genetic background. Using
      a modifier approach, we derive analytical results under the assumption of weak
      selection and constant population size, and we investigate the full model by
      numerical simulations. We find that frequency-dependent disruptive selection
      favors the evolution of a highly asymmetric genetic architecture, where most of
      the genetic variation is concentrated on a small number of loci. We show that the
      evolution of genetic architecture can be understood in terms of the ecological
      niches created by competition. The phenotypic distribution of a population with
      an adapted genetic architecture closely matches this niche structure. Thus,
      evolution of the genetic architecture seems to be a plausible way for populations
      to adapt to regimes of frequency-dependent disruptive selection. As such, it
      should be seen as a potential evolutionary pathway to discrete polymorphisms and
      as a potential alternative to other evolutionary responses, such as the evolution
      of sexual dimorphism or assortative mating.

PMID- 17017056
TI  - Isolation by resistance.
AB  - Despite growing interest in the effects of landscape heterogeneity on genetic
      structuring, few tools are available to incorporate data on landscape composition
      into population genetic studies. Analyses of isolation by distance have typically
      either assumed spatial homogeneity for convenience or applied theoretically
      unjustified distance metrics to compensate for heterogeneity. Here I propose the
      isolation-by-resistance (IBR) model as an alternative for predicting equilibrium
      genetic structuring in complex landscapes. The model predicts a positive
      relationship between genetic differentiation and the resistance distance, a
      distance metric that exploits precise relationships between random walk times and
      effective resistances in electronic networks. As a predictor of genetic
      differentiation, the resistance distance is both more theoretically justified and
      more robust to spatial heterogeneity than Euclidean or least cost path-based
      distance measures. Moreover, the metric can be applied with a wide range of data
      inputs, including coarse-scale range maps, simple maps of habitat and nonhabitat
      within a species' range, or complex spatial datasets with habitats and barriers
      of differing qualities. The IBR model thus provides a flexible and efficient tool
      to account for habitat heterogeneity in studies of isolation by distance, improve
      understanding of how landscape characteristics affect genetic structuring, and
      predict genetic and evolutionary consequences of landscape change.

PMID- 17017057
TI  - Variation in resistance and virulence in the interaction between Arabidopsis
      thaliana and a bacterial pathogen.
AB  - We examined patterns of variation and the extent of local adaptation in the
      interaction between the highly selfing annual weed Arabidopsis thaliana and its
      foliar bacterial pathogen Pseudomonas viridiflava by cross-infecting 23 bacterial
      isolates with 35 plant lines collected from six fallow or cultivated fields in
      the Midwest, USA. We used two measures of resistance and virulence: bacterial
      count in the leaf and symptom development four days after infection. We found
      variation in resistance in A. thaliana and virulence in P. viridiflava, as well
      as a significant difference in symptoms between two distinct genetic clades
      within P. viridiflava. We also observed that both resistance and plant
      development rate varied with field type of origin (cultivated or fallow),
      possibly through age-related resistance, a developmentally regulated general form
      of resistance. Finally, we did not observe local adaptation by host or pathogen,
      rather we found patterns of variation across populations that depended in part on
      P. viridiflava clade. These data suggest that the interaction between A. thaliana
      and P. viridiflava varies across space and is mediated by the selection regime of
      the host populations and differential performance of the P. viridiflava clades.
      This is one of a very limited number of studies examining a bacterial pathogen of
      wild plant populations and one of a few studies to examine patterns of variation
      in a plant-pathogen association that is not a highly specialized gene-for-gene
      interaction.

PMID- 17017058
TI  - Population differentiation and genetic variation in host choice among pea aphids
      from eight host plant genera.
AB  - Habitat choice plays a critical role in the processes of host range evolution,
      specialization, and ecological speciation. Pea aphid, Acyrthosiphon pisum,
      populations from alfalfa and red clover in eastern North America are known to be
      genetically differentiated and show genetic preferences for the appropriate host
      plant. This species feeds on many more hosts, and here we report a study of the
      genetic variation in host plant preference within and between pea aphid
      populations collected from eight genera of host plants in southeastern England.
      Most host-associated populations show a strong, genetically based preference for
      the host plant from which they were collected. Only in one case (populations from
      Vicia and Trifolium) was there little difference in the plant preference spectrum
      between populations. All populations showed a significant secondary preference
      for the plant on which all the aphid lines were reared: broad bean, Vicia faba,
      previously suggested to be a "universal host" for pea aphids. Of the total
      genetic variance in host preference within our sample, 61% could be attributed to
      preference for the collection host plant and a further 9% to systematic
      differences in secondary preferences with the residual representing within
      population genetic variation between clones. We discuss how a combination of host
      plant preference and mating on the host plant may promote local adaptation and
      possibly ecological speciation, and whether a widely accepted host could oppose
      speciation by mediating gene flow between different populations.

PMID- 17017059
TI  - Fitness consequences of hybridization between ecotypes of Avena barbata: hybrid
      breakdown, hybrid vigor, and transgressive segregation.
AB  - Hybridization is an important factor in the evolution of plants; however, many of
      the studies that have examined hybrid fitness have been concerned with the study
      of early generation hybrids. We examined the early- and late-generation fitness
      consequences of hybridization between two ecotypes of the selfing annual Avena
      barbata in a greenhouse environment as well as in two natural environments.
      Fitness of early generation (F2) hybrids reflects both the action of dominance
      effects (hybrid vigor) and recombination (hybrid breakdown) and was not
      significantly different from that of the midparent in any environment. Fitness of
      later generation (F6) recombinant inbred lines (RILS) derived from the cross
      reflect both the loss of early generation heterozygosity as well as disruption of
      any coadapted gene complexes present in the parents. In all environments, F6 RILs
      were on average significantly less fit than the (equally homozygous) midparent,
      indicating hybrid breakdown through the disruption of epistatic interactions.
      However, the inbred F6 were also less fit than the heterozygous F2, indicating
      that hybrid vigor also occurs in A. barbata, and counteracts hybrid breakdown in
      early generation hybrids. Also, although the F6 generation mean is lower than the
      midparent mean, there are individual genotypes within the F6 generation that are
      capable of outperforming the parental ecotypes in the greenhouse. Fewer hybrid
      genotypes are capable of outperforming the parental ecotypes in the field.
      Overall, these experiments demonstrate how a single hybridization event can
      result in a number of outcomes including hybrid vigor, hybrid breakdown, and
      transgressive segregation, which interact to determine long-term hybrid fitness.

PMID- 17017060
TI  - Macroevolutionary data suggest a role for reinforcement in pollination system
      shifts.
AB  - Reproductive isolation can evolve either as a by-product of divergent selection
      or through reinforcement. We used the Cape flora of South Africa, known for its
      high level of pollination specialization, as a model system to test the potential
      role of shifts in pollination system in the speciation process. Comparative
      analysis of 41 sister-species pairs (representing Geraniaceae, Iridaceae, and
      Orchidaceae) for which complete pollinator, edaphic, and distribution data are
      available showed that for sister species with overlapping distribution ranges,
      pollination system shifts are significantly associated with edaphic shifts. In
      contrast, there is no significant association between pollination system shifts
      and edaphic shifts for allopatric sister species. These results are interpreted
      as evidence for reinforcement.

PMID- 17017061
TI  - Environmental heterogeneity and the maintenance of genetic variation for
      reproductive diapause in Drosophila melanogaster.
AB  - Drosophila melanogaster has colonized temperate habitats on multiple continents
      over a historical time period, and many traits vary predictably with latitude.
      Despite considerable attention paid to clinal variation in Drosophila, the
      mechanisms generating such patterns in nature remain largely unidentified. In D.
      melanogaster, the expression of reproductive diapause can be induced by exposure
      to low temperatures and shortened photoperiods. Both diapause expression itself
      and the underlying genetic variance for diapause expression have widespread
      impacts on organismal fitness, and diapause incidence exhibits a 60% cline in
      frequency in the eastern United States. The major aim of this study was to
      evaluate whether the relative fitness of diapause and nondiapause genotypes
      varies predictably with environment. In experimental population cages in the
      laboratory, the frequency of genotypes that express diapause increased over time
      when flies were exposed to environmental stress, whereas the frequency of
      nondiapause genotypes increased when flies were cultured under benign control
      conditions. Other fitness traits correlated with the genetic variance for
      diapause expression (longevity, mortality rates, stress resistance, lipid
      content, preadult viability, fecundity profiles, and development time) also
      diverged between experimental treatments. Similarly, sampling of isofemale lines
      from natural populations revealed that the frequency of diapause incidence cycled
      over time in seasonal habitats: diapause expression was at high frequency
      following the winter season and subsequently declined throughout the summer
      months. In contrast, diapause expression was low and temporally homogeneous in
      isofemale line collections from human-associated urban habitats. These data
      suggest that genetic variation underlying the diapause-nondiapause dichotomy may
      be actively maintained by selection pressures that vary spatially and temporally
      in natural populations.

PMID- 17017062
TI  - Responses to selection on phenoloxidase activity in yellow dung flies.
AB  - Maintaining an immune system is costly. Resource allocation to immunity should
      therefore trade off against other fitness components. Numerous studies have found
      phenotypic trade-offs after immune challenge, but few have investigated genetic
      correlations between immune components and other traits. Furthermore, empirical
      evidence for the costs of maintaining an innate immune system in the absence of
      challenges is rare. We examined responses to artificial selection on
      phenoloxidase (PO) activity, an important part of the insect innate defense
      against multicellular pathogens, in yellow dung flies, Scathophaga stercoraria
      (L.). After 15 generations of successful selection on PO activity, we measured
      reproductive characters: clutch size, egg hatching rates, adult emergence rates,
      and adult longevity. We found no evidence for negative genetic correlations
      between PO activity and reproduction. In fact, flies of lines selected for
      increased PO activity had larger first clutches, and flies of lines selected for
      decreased PO activity had smaller ones. However, flies from high-PO lines died
      earlier than did low-PO flies when no food was available; that is, there is a
      survival cost of running at high PO levels in the absence of challenge. Variation
      in resource acquisition or use may lead to positive genetic correlations between
      PO and fertility and fecundity. The negative correlation between PO and longevity
      under starvation may indicate that variation for resource acquisition is
      maintained by a cost of acquisition, based on a genotype-environment interaction.

PMID- 17017063
TI  - Larval habits, host-plant associations, and speciation in nematine sawflies
      (Hymenoptera: Tenthredinidae).
AB  - Adaptive radiations consist of two intertwined processes, diversification of
      species and diversification of their ecological niches, but it is unclear whether
      there is a causal link between the processes. In phytophagous insects, ecological
      diversification mainly involves shifts in host-plant associations and in larval
      feeding habits (internal or external) on different plant parts, and several
      observations indicate that speciation is facilitated by host shifts. Data on host
      use in individual species suggest that internal feeders are less likely to
      colonize new hosts than external-feeding taxa and, consequently, increases in
      collective host ranges and species numbers should be slowed down in endophagous
      lineages. We tested these related hypotheses by using phylogenetic information to
      reconstruct the evolutionary history of larval resource use in the sawfly
      subfamily Nematinae, a group of 1000 plus species with a broad range of niches:
      the subfamily's combined host range includes over 20 plant families, and larvae
      may feed externally on leaves or needles, or internally, for example, in buds,
      fruits, leaves, or galls. The results show that: (1) Most internally feeding
      groups have evolved independently from external-feeding ancestors, but several
      distinct internal habits have appeared convergently multiple times; (2) Shifts
      among host taxa are clearly more common than changes in larval habits; (3) The
      majority of host switches have occurred among phylogenetically close plant
      groups, but many shifts are manifest among distantly related, ecologically
      proximate hosts; (4) Although external feeding characteristic of the common
      ancestor of Nematinae is associated with relatively high rates of host-shifting,
      internal feeders are very conservative in their host use; (5) In contrast, the
      effect of endophagy on speciation probabilities is more variable: net speciation
      rates are lowered in most internal-feeding groups, but a striking exception is
      found in species that induce galls on Salicaceae. The loose connection between
      collective host ranges and species diversity provides empirical support for
      theoretical models suggesting that speciation rates are a function of a complex
      interplay between "intrinsic" niche width and resource heterogeneity.

PMID- 17017064
TI  - Male genotype affects female fitness in a paternally investing species.
AB  - Male nutrient provisioning is widespread in insects. Females of some species use
      male-derived nutrients for increased longevity and reproductive output. Despite
      much research into the consequences of paternal nutrient investment for male and
      female fitness, the heritability, and therefore the potential of this trait to
      respond to selection, has rarely been examined. Males of several butterfly
      species provide the female with nutrients in the spermatophore at mating. Females
      of the green-veined white butterfly Pieris napi (Lepidoptera: Pieridae) use male
      donations both for developing eggs (resulting in higher lifetime fecundity of
      multiply mated females), but also for their somatic maintenance (increasing
      longevity). Using half-sib, father-son regression and full-sib analyses, I showed
      that paternal nutrient investment is heritable, both in terms of the absolute but
      also the relative size of the spermatophore (controlling for body size). Male
      size and spermatophore size were also genetically correlated. Furthermore, a
      separate study showed male genotype had a significant effect on female longevity
      and lifetime fecundity. In contrast, male genotype had no influence on the
      immediate egg-laying rate of females following mating, suggesting limited scope
      for male manipulation of immediate female oviposition. These results indicate
      that females may derive both direct (increased lifetime fecundity and longevity)
      and indirect (sons with greater reproductive success) fitness benefits from
      paternal nutrient donations in this species.

PMID- 17017065
TI  - Rare sexual reproduction events in the clonal reproduction system of introduced
      populations of the little fire ant.
AB  - A unique reproductive system has previously been described in Wasmannia
      auropunctata, a widespread invasive ant species, where males are produced
      clonally, female queens are parthenogens, and female workers are produced
      sexually. However, these findings were mostly based on samples originating from
      only a limited part of the native range of the species in South America. We used
      microsatellite markers to uncover the reproductive modes displayed by a large
      number of nests collected in various invasive W. auropunctata populations
      introduced 40 years ago into New Caledonia, where the species now forms a single
      450-km-long supercolony. Although the main reproduction system in New Caledonia
      remained clonality for both male and female reproductives, we found evidence of
      rare sexual reproduction events that led to the production of both new queen and
      male clonal lineages. All clonal lineages observed in New Caledonia potentially
      derived from sexual reproduction, recombination, and mutation events from a
      single female and a single male genotype. Hence, the male and female gene pools
      are not strictly separated in New Caledonia and the two sexes do not follow
      independent evolutionary trajectories. Our results also suggest genetic
      determination for both parthenogenesis and caste. We discuss the evolutionary
      implications of the emergence of sex in the clonal reproduction system of
      introduced populations of W. auropunctata.

PMID- 17017066
TI  - Local heterozygosity-fitness correlations with global positive effects on fitness
      in threespine stickleback.
AB  - The complex interactions between genetic diversity and evolution have important
      implications in many biological areas including conservation, speciation, and
      mate choice. A common way to study these interactions is to look at
      heterozygosity-fitness correlations (HFCs). Until recently, HFCs based on
      noncoding markers were believed to result primarily from global inbreeding
      effects. However, accumulating theoretical and empirical evidence shows that HFCs
      may often result from genes being linked to the markers used (local effect).
      Moreover, local effect HFCs could differ from global inbreeding effects in their
      direction and occurrence. Consequently, the investigation of the structure and
      consequences of local HFCs is emerging as a new important goal in evolutionary
      biology. In this study of a wild threespine stickleback (Gasterosteus aculeatus)
      population, we first tested the presence of significant positive or negative
      local effects of heterozygosity at 30 microsatellites loci on five fitness
      components: survival, mating success, territoriality, length, and body condition.
      Then, we evaluated the direction and shape of total impact of local HFCs, and
      estimated the magnitude of the impacts on fitness using regression coefficients
      and selection differentials. We found that multilocus heterozygosity was not a
      reliable estimator of individual inbreeding coefficient, which supported the
      relevance of single-locus based analyses. Highly significant and temporally
      stable local HFCs were observed. These were mainly positive, but negative effects
      of heterozygosity were also found. Strong and opposite effects of heterozygosity
      are probably present in many populations, but may be blurred in HFC analyses
      looking for global effects only. In this population, both negative and positive
      HFCs are apparently driving mate preference by females, which is likely to
      contribute to the maintenance of both additive and nonadditive genetic variance.

PMID- 17017067
TI  - Geographic variation of genetic and behavioral traits in northern and southern
      tungara frogs.
AB  - We use a combination of microsatellite marker analysis and mate-choice behavior
      experiments to assess patterns of reproductive isolation of the tungara frog
      Physalaemus pustulosus along a 550-km transect of 25 populations in Costa Rica
      and Panama. Earlier studies using allozymes and mitochondrial DNA defined two
      genetic groups of tungara frogs, one ranging from Mexico to northern Costa Rica
      (northern group), the second ranging from Panama to northern South America
      (southern group). Our more fine-scale survey also shows that the northern and
      southern tungara frogs are genetically different and geographically separated by
      a gap in the distribution in central Pacific Costa Rica. Genetic differences
      among populations are highly correlated with geographic distances. Temporal call
      parameters differed among populations as well as between genetic groups.
      Differences in calls were explained better by geographic distance than by genetic
      distance. Phonotaxis experiments showed that females preferred calls of males
      from their own populations over calls of males from other populations in about
      two-thirds to three-fourths of the contrasts tested. In mating experiments,
      females and males from the same group and females from the north with males from
      the south produced nests and tadpoles. In contrast, females from the south did
      not produce nests or tadpoles with males from the north. Thus, northern and
      southern tungara frogs have diverged both genetically and bioacoustically. There
      is evidence for some prezygotic isolation due to differences in mate recognition
      and fertilization success, but such isolation is hardly complete. Our results
      support the general observation that significant differences in sexual signals
      are often not correlated with strong genetic differentiation.

PMID- 17017068
TI  - Using spectral data to reconstruct evolutionary changes in coloration: carotenoid
      color evolution in New World orioles.
AB  - Carotenoid-based colors are thought to play an important signaling role in many
      animal taxa. However, little is known about evolutionary changes in carotenoid
      coloration, especially among closely related species. We used a phylogenetic
      perspective to examine carotenoid color changes within New World orioles (genus
      Icterus). Oriole color was quantitatively measured using reflectance
      spectrometry. We found continuous variation from short- to long-wavelength
      carotenoid colors in extant orioles--perceived by humans as ranging from yellow
      to scarlet--suggesting that these carotenoid-based colors have evolved as a
      continuous character. Ancestral state reconstruction suggests that short- and
      long-wavelength carotenoid colors have evolved independently multiple times,
      likely from a middle-wavelength ancestor. Although color showed considerable
      lability, we found a significant amount of phylogenetic signal across the entire
      genus. This implies that while labile, the colors of closely related taxa tended
      to resemble each other more than would be expected due to chance. To our
      knowledge, this is the first study to use quantitative character states derived
      from reflectance spectra in ancestral state reconstruction. Reflectance spectra
      provide an unbiased quantitative description of color that allowed us to detect
      subtle changes among closely related taxa. Using these quantitative methods to
      score and reconstruct color changes among closely related taxa provides a better
      understanding of how elaborate animal colors evolve.

PMID- 17017069
TI  - Growth strategies of passerine birds are related to brood parasitism by the brown
      headed cowbird (Molothrus ater).
AB  - Sibling competition was proposed as an important selective agent in the evolution
      of growth and development. Brood parasitism by the brown-headed cowbird
      (Molothrus ater) intensifies sibling competition in the nests of its hosts by
      increasing host chick mortality and exposing them to a genetically unrelated
      nestmate. Intranest sibling competition for resources supplied by parents is size
      dependent. Thus, it should select for high development rates and short nestling
      periods, which would alleviate negative impacts of brood parasitic chicks on host
      young. I tested these predictions on 134 North American passerines by comparative
      analyses. After controlling for covariates and phylogeny, I showed that high
      parasitism rate was associated with higher nestling growth rate, lower mass at
      fledging, and shorter nestling periods. These effects were most pronounced in
      species in which sibling competition is most intense (i.e., weighing over about
      30 g). When species were categorized as nonhosts versus old hosts (parasitized
      for thousands of years) versus new hosts (parasitized the last 100-200 years),
      there was a clear effect of this parasitism category on growth strategies.
      Nestling growth rate was the most evolutionarily flexible trait, followed by mass
      at fledging and nestling period duration. Adjustments during incubation
      (incubation period length, egg volume) were less pronounced and generally
      disappeared after controlling for phylogeny. I show that sibling competition
      caused by brood parasites can have strong effects on the evolution of host growth
      strategies and that the evolution of developmental traits can take place very
      rapidly. Human alteration of habitats causing spread of brood parasites to new
      areas thus cascades into affecting the evolution of life-history traits in host
      species.

PMID- 17017070
TI  - Conserved phenotypic variation patterns, evolution along lines of least
      resistance, and departure due to selection in fossil rodents.
AB  - Within a group of organisms, some morphologies are more readily generated than
      others due to internal developmental constraints. Such constraints can channel
      evolutionary changes into directions corresponding to the greatest intraspecific
      variation. Long-term evolutionary outputs, however, depend on the stability of
      these intraspecific patterns of variation over time and from the interplay
      between internal constraints and selective regimes. To address these questions,
      the relationship between the structure of phenotypic variance covariance matrices
      and direction of morphological evolution was investigated using teeth of fossil
      rodents. One lineage considered here leads to Stephanomys, a highly specialized
      genus characterized by a dental pattern supposedly favoring grass eating.
      Stephanomys evolved in the context of directional selection related to the
      climatic trend of global cooling causing an increasing proportion of grasslands
      in southwestern Europe. The initial divergence (up to approximately 6.5 mya) was
      channeled along the direction of greatest intraspecific variation, whereas after
      6.5 mya, morphological evolution departed from the direction favored by internal
      constraints. This departure from the "lines of least resistance" was likely the
      consequence of an environmental degradation causing a selective gradient strong
      enough to overwhelm the constraints to phenotypic evolution. However, in a
      context of stabilizing selection, these constraints actually channel evolution,
      as exemplified by the lineage of Apodemus. This lineage retained a primitive diet
      and dental pattern over the last 10 myr. Limited morphological changes occurred
      nevertheless in accordance with the main patterns of intraspecific variation. The
      importance of these lines of least resistance directing long-term morphological
      evolution may explain parallel evolution of some dental patterns in murine
      evolution.

PMID- 17017071
TI  - Restricted gene flow at specific parts of the shrew genome in chromosomal hybrid
      zones.
AB  - The species and races of the shrews of the Sorex araneus group exhibit a broad
      range of chromosomal polymorphisms. European taxa of this group are parapatric
      and form contact or hybrid zones that span an extraordinary variety of
      situations, ranging from absolute genetic isolation to almost free gene flow.
      This variety seems to depend for a large part on the chromosome composition of
      populations, which are primarily differentiated by various Robertsonian fusions
      of a subset of acrocentric chromosomes. Previous studies suggested that
      chromosomal rearrangements play a causative role in the speciation process. In
      such models, gene flow should be more restricted for markers on chromosomes
      involved in rearrangements than on chromosomes common in both parent species. In
      the present study, we address the possibility of such differential gene flow in
      the context of two genetically very similar but karyotypically different hybrid
      zones between species of the S. araneus group using microsatellite loci mapped to
      the chromosome arm level. Interspecific genetic structure across rearranged
      chromosomes was in general larger than across common chromosomes. However, the
      difference between the two classes of chromosomes was only significant in the
      hybrid zone where the complexity of hybrids is expected to be larger. These
      differences did not distinguish populations within species. Therefore, the
      rearranged chromosomes appear to affect the reproductive barrier between
      karyotypic species, although the strength of this effect depends on the
      complexity of the hybrids produced.

PMID- 17017072
TI  - The island rule in large mammals: paleontology meets ecology.
AB  - The island rule is the phenomenon of the miniaturization of large animals and the
      gigantism of small animals on islands, with mammals providing the classic case
      studies. Several explanations for this pattern have been suggested, and
      departures from the predictions of this rule are common among mammals of
      differing body size, trophic habits, and phylogenetic affinities. Here we offer a
      new explanation for the evolution of body size of large insular mammals, using
      evidence from both living and fossil island faunal assemblages. We demonstrate
      that the extent of dwarfism in ungulates depends on the existence of competitors
      and, to a lesser extent, on the presence of predators. In contrast, competition
      and predation have little or no effect on insular carnivore body size, which is
      influenced by the nature of the resource base. We suggest dwarfism in large
      herbivores is an outcome of the fitness increase resulting from the acceleration
      of reproduction in low-mortality environments. Carnivore size is dependent on the
      abundance and size of their prey. Size evolution of large mammals in different
      trophic levels has different underlying mechanisms, resulting in different
      patterns. Absolute body size may be only an indirect predictor of size evolution,
      with ecological interactions playing a major role.

PMID- 17017073
TI  - Confounding asymmetries in evolutionary diversification and character change.
AB  - Studies of character evolution often assume that a phylogeny's shape is
      determined independently of the characters, which then evolve as mere passengers
      along the tree's branches. However, if the characters help shape the tree, but
      this is not considered, biased inferences can result. Simulations of asymmetrical
      speciation (i.e., one character state conferring a higher rate of speciation than
      another) result in data that are interpreted to show a higher rate of change
      toward the diversification-enhancing state, even though the rates to and from
      this state were in fact equal. Conversely, simulations of asymmetrical character
      change yield data that could be misinterpreted as showing asymmetrical rates of
      speciation. Studies of biased diversification and biased character change need to
      be unified by joint models and estimation methods, although how successfully the
      two processes can be teased apart remains to be seen.

PMID- 17017074
TI  - [Past, present and future of pediatric cardiology].

PMID- 17017075
TI  - [Approach to congenital heart disease in adults].
AB  - After a few decades treating patients with congenital heart disease during
      childhood, we now face the problem of dealing with many of them as adults and few
      cases with disorders detected in adult life. The number of patients, with and
      without surgery is growing up rapidly. Conservatively speaking, there are in
      Mexico approximately 300 thousands patients with this condition, increasing by 15
      thousands patients per year. In addition to the complexity of the congenital
      pathology, the knowledge of acquired diseases should be incorporated as well as
      the genetic advise, pregnancy care and specialized psychological support. The
      approach to these patients begins with stratification; diagnosis and treatment
      requiring a multidisciplinary, well informed and an capable to perform together
      medical team.

PMID- 17017076
TI  - [Ventricular arrhythmias and conduction disturbances in patients with corrected
      tetralogy of Fallot].
AB  - Tetralogy of Fallot is the most common cyanotic heart disease. Corrective
      intracardiac repair has been performed for >40 years with excellent results.
      Nevertheless ventricular arrhythmias have consistently been reported, and sudden
      cardiac death is the most common cause of mortality late after repair. Programmed
      ventricular stimulation has been used in selected patients at many centers;
      however, attempts to clarify its predictive value have been limited by small
      patient number and relatively low event rates. The emergence of successful
      methods for both the prevention of arrhythmias, (including electrophysiological
      ablation and implantable defibrillators), has meant the identification of those
      at risk of even greater importance.

PMID- 17017078
TI  - [Pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension is a progressive and lethal disease for which
      there is no effective cure. In recent years, however, there has been a
      significant progress in the knowledge about the pathobiologic mechanisms involved
      in the characteristic vascular damage of this disease. Knowledge has evolved from
      the importance of the vasoconstriction component originally contemplated to the
      current concept of a preponderant abnormal (fibromuscular) proliferation. This
      conceptual evolution has resulted in new and attractive pharmacologic
      interventions in an attempt to interrupt this abnormal process of vascular
      remodeling. In this review, the interventions derived from this pathobiologic
      knowledge are analyzed and based on the most recent controlled clinical trials;
      an evidence-based therapeutic strategy is established.

PMID- 17017077
TI  - [Ebstein anomaly].
AB  - We evaluated the results for primary repair of Ebstein anomaly in 61 patients,
      both adults and children. The records were reviewed of patients undergoing repair
      of Ebstein anomaly at the Congenital Heart Surgery Service of the National
      Institute of Cardiology "Ignacio Chavez" from January 1993 to August 2003.
      Functional, demographic, and echocardiographic parameters were studied both
      preoperatively and postoperatively, along with functional status and adverse
      events. The repair technique involved vertical plication of the atrialized
      ventricle and valve leaflet reimplantation after clockwise rotation or
      replacement of tricuspid valve. Ebstein repair has good functional outcomes in
      patients despite residual tricuspid regurgitation, likely because of reduction in
      right ventricular volume loading and relative annular and ventricular plasticity.
      Intraoperative radiofrequency ablation represents an important adjunctive
      treatment for intractable arrhythmias, which may now represent relative
      indications for operative intervention.

PMID- 17017079
TI  - [Advances in the pathophysiology and treatment of postoperative pulmonary
      hypertension].
AB  - Pulmonary hypertension is a condition frequently seen and associated to many
      cardiovascular diseases and can become a hemodynamic complication in
      postoperative period. This can require the integral management in the intensive
      care room. In the last years we have many new concepts about the pathophysiology
      of this condition and new therapeutic options. In this paper we review the
      current strategies for the management of this condition.

PMID- 17017080
TI  - [Update of the pulmonary artery catheter in cardiac surgery].
AB  - The pulmonary Artery Catheter was introduced 30 years ago in the clinical
      practice, one of the main uses is cardiac surgery. There are attempts to
      substitute hemodynamic values obtained by the catheter with the use of
      noninvasive devices but none has successfully used, there are several controversy
      areas based in the utility of the catheter, finding contradictory literature
      reports, most studies reefers generally to the surgical patient, there are no
      studies in cardiac surgery, several groups have published statements, they
      recommended a indication tailored to the hemodynamic status and three
      interrelated variables to be assessed; patient factors, procedure factors and
      practice setting factors. The conclusion is the pulmonary artery catheter is only
      a monitoring device, the value of the hemodiynamic parameters obtained lies in
      the medical team.

PMID- 17017081
TI  - [Risk of blood transfusion in cardiac surgery].
AB  - Bleeding occur frequently in patients undergoing cardiac surgery. Although
      unexpected bleeding after this surgery is common, reducing this bleeding is a
      desirable clinical goal, because such bleeding is associated with adverse
      outcomes. Bleeding during and after cardiac operations and the hemodilution
      effects of cardiopulmonary bypass commonly result in blood transfusions. Despite
      institutional efforts to curtail the frequency of blood transfusions in cardiac
      operation, the frequency remains high. If transfusions were completely safe,
      differing thresholds would not matter. However, the adverse reactions associated
      with transfusions are: febrile reactions, hemolytic and infectious complications
      may occur. Most recently, blood transfusions have been linked to postoperative
      wound infections, pneumonia, renal dysfunction, severe sepsis, hospital mortality
      and increased 5-year mortality.

PMID- 17017082
TI  - [Systemic inflammatory response in pediatric cardiac surgery].
AB  - Systemic Inflammatory Response (SIR) constitutes generalized, non-specific
      response to tissue injury of whatever etiology, and is a rapid, highly amplified,
      controlled humeral and cellular response. Cardiopulmonary Bypass (CPB) is
      necessary in many cardiac surgery as in adults as children. Also we know the
      undesirable effects of SIR. The pediatric surgical team to treat of management
      very well if exist the threat of undesirable outcome after CPB. There are several
      key components of the inflammatory response to cardiac surgery involve the
      complement, immune and endothelial systems. Cytokines may exert either
      proinflammatory or antiinflammatory effects. Cytokines are essential for
      immunologic and physiologic homeostasis, are normally subject to thight
      homeostatic control, and are produced in response to a variety of physiologic and
      pathologic stimuli. An uncontrolled inflammatory response appears to play a
      significant role in the morbidity or mortality observed in patients undergoing
      CPB. The inflammatory response contributes to the pathogenesis of acute
      pulmonary, cardiovascular, neurologic, splanchnic, hematologic, and immune system
      dysfunction following cardiac surgery. The development of strategies to control
      the inflammatory response following cardiac surgery is currently the focus of
      considerable research efforts. Diverse techniques, including maintenance of
      hemodynamic stability, minimization of exposure to CPB circuitry, and
      pharmacologic and immunomodulatory agents have been studied. Also hemofiltration,
      leukodepletion, the use of serine protease inhibitors and corticosteroids.
      Molecular biology is revolutionizing medicine and the ability to assess the
      impact of genetic variability on disease characterization and perioperative
      outcome. Recent evidence suggests that the degree and severity of surgical
      induced inflammation may be significantly influenced by genotype.

PMID- 17017083
TI  - [Oxygen carriers in cardiac surgery].
AB  - Artificial oxygen carriers may be grouped into two categories: Hemoglobin-based
      solutions and perfluoro-chemical based emulsions. Allogenic erythrocyte
      transfusions represent a limited resource and are associated with adverse events
      such as acute transfusion reactions, transmission of infectious diseases,
      immunosuppression and postoperative infections. Although "artificial blood" is
      not yet a clinical reality, several temporary "artificial oxygen carriers" are in
      late stage clinical development.

PMID- 17017084
TI  - [Stentless bioprostheses they are better?].
AB  - The history and evolution of the bioprostheses is revised, above all the
      stentless. According to the international literature these were the first
      prosthesis that were established to cardiac level with very good results in the
      haemodynamic aspect, but that to lack an adequate preparation to diminish its
      antigenicity, to enlarge its resistance and to avoid the deterioration by
      calcification, less lasting than the mechanics did them. Nevertheless, it given
      that the real valvular area is much better than in all the other prostheses,
      their magnificent haemodynamic performance, the not mandatory use of
      anticoagulants, they do it a good offering for the patients with valvulopathy,
      above all the aortic. That international experience, now also shows how the use
      of anticalcification has improved even more the performance of these prostheses,
      to enlarge considerably its useful time of long-term life, reasons these by that
      are being utilized in form increasingly more extensive, above all indicating its
      use in patients more young, which before was almost prohibitive. Finally the
      initial experience with these bioprotheses in the National Institute of
      Cardiology of Mexico is mentioned.

PMID- 17017085
TI  - [Coronary revascularization surgery without cross-clamping, advantages and
      outcomes].
AB  - The Coronary revascularization surgery has been the best option to treatment of
      ischemic heart disease. However, as a result of the advent of hemodynamic
      procedures, the complexity of the patients subject to surgery, increase
      importantly. For this cause the surgeons has modified their techniques and has
      arisen the off-pump coronary revascularization surgery. This technique cause a
      low inflammatory response and accordingly low organic damage to avoid the
      extracorporeal circulation and the "Pump exit"; nevertheless in many cases are
      incomplete, more complex, uncomfortable and not practicable in all patients. For
      this reason has appeared a procedure to allow a join between the advantages of
      without aortic cross-clamping and the security of the circulatory assistance to
      patient: The Coronary revascularization surgery without cross-clamping with
      circulatory assistance,and heart-beating. To determine the results of the
      Coronary revascularization surgery without aortic cross-clamping with circulatory
      assistance and heart-beating we studied 64 patients with ischemic heart disease
      of March of 2002 to May of 2005. In comparison with conventional surgery, the
      bleeding, mediastinitis, perioperative infarct to heart and cerebrovascular
      accident was not significant (p = 0.12-0.34) however the mortality was more low
      (p < 0.05) in this group (7.40%) in comparison with conventional surgery (8.79%).

PMID- 17017086
TI  - [Surgical treatment of aortic stenosis in small aortic annulus].
AB  - The purpose of this work is to demonstrate that the aortic enlargement
      procedures, first described for patients with small aortic annulus, are
      reproducible with excellent results. A retrospective revision of 72 cases in
      which an enlargement procedure was done, with consideration regarding the
      relationship between valve size and patient body surface area, in order to avoid
      prosthesis-patient mismatch, was done. We consider the immediate mortality of the
      group, differentiating the cardiac mortality, concluding with other authors that
      body surface areas between 1.3 and 1.7 m2 should receive aortic prosthesis larger
      than #23, which will eventually improve the late outcome of this population. We
      demonstrate that the aortic annular enlargement procedures can be safely done in
      our hospital, with a slight increase in mortality during the learning phase, but
      great benefit afterwards.

PMID- 17017087
TI  - [The aortic aneurysms and therapeutic management].
AB  - The aorta was saw has a tube who transport blood from the heart to all the human
      economy, today we see the aorta like an specific organ who not only is design to
      transport the blood and it is elements, the aorta also produce hormones and
      elements of the inflammatory responds and control the systemic pressure. That's
      why the aorta has it specific illness. In the entire world the pathology of the
      aorta is quite frequent with the appearance of a lot of new cases and occupies a
      predominant place in the general mortality of countries like United States of
      America, Japan or Brazil. This pathology needs the utilization of large amounts
      of economics, human and structural resources. In Mexico do not have the
      statistical information of the aortic illness because it is few diagnosed, and
      when induce death it confusing to another diseases. In the present time with the
      new no invasive diagnostic methods more approachable to the general population
      this disease is easier to diagnose. That is why he need to develop a
      multidisciplinary specialize group who can make the diagnosed and do the specific
      treatment for these disease.

PMID- 17017088
TI  - [From 2D to 4D echocardiography in adults with congenital heart disease].
AB  - In the present publication an analysis of the utility is done of the
      Echocardiography, and its different modalities, in the diagnosis of patient adult
      with Congenital Heart disease. Special emphasis since the view 2-D to the view in
      4-D.

PMID- 17017089
TI  - [Diagnostic catheterization in grown up congenital heart disease].
AB  - Non invasive techniques are the procedures of choice in the assessment of the
      adult patient with congenital heart disease. Currently cardiac catheterization is
      mainly pointed towards interventional purposes; however in some cases such as
      complex congenital heart conditions, it is a valuable auxiliary method. Preassure
      measurements, oximetry and angiography are fundamental in the assessment of
      patients with selected cardiac disease without treatment; palliative or
      corrective surgery.

PMID- 17017090
TI  - [Application of cardiovascular magnetic resonance in congenital heart disease].
AB  - Cardiovascular magnetic resonance (CVMR) is the best non invasive imaging
      technique for the diagnosis of congenital heart disease (CHD) as it gives
      important information concerning anatomy and function of the heart in the same
      exploration. This method is useful for the follow up of the patient with
      congenital heart disease. The most important benefits of CVMR are the non
      invasiveness of the same and the lack of ionic radiation. The objective of this
      article is to demonstrate that congenital heart disease can be diagnosed with
      CVMR with a higher precision compared with other cardiovascular imaging
      techniques.

PMID- 17017091
TI  - [Noninvasive and invasive diagnosis of congenital heart disease].
AB  - One carries out retrospective study to evaluate the paper that had in our
      Institution, the echocardiogram for the surgical indication, the necessity to
      supplement with other diagnostic methods and if there was discrepancy between the
      diagnostic echocardiography and the surgical finding. A the files were revised of
      patient smaller than 18 years that were subjected to surgical correction of their
      congenital heart defect among January 19 at June 30 2003. The patients grouped
      according to the RACHS-1 in 6 groups of surgical risk and the conclusions were
      obtained you diagnose echocardiography, the established surgical plan as well as
      the operative discoveries and the finally carried out surgery type. In the
      studied period they were carried out to heart surgeries of risk 1, 16 patients
      (11%); risk 2, 59 patients (43%); risk 3, 52 patients (38%) and 9 patients (6%)
      the risk 4. There were 9 deaths (6%), 6 were of the group of risk 3; three of the
      group 2, being 7 patients (77%) smaller than 1 year. They were taken to surgery
      without catheterize study 62% of the patients. The patients that were subjected
      to previous catheterize to the surgery, the indication was the complexity of the
      cardiopathy in 70.8%, for some procedure interventionist in 20% and it stops
      evaluation of the lung hypertension in 8%. In 28 patients (20%) there was not
      agreement between the surgical discoveries and the one I diagnose
      echocardiography basically to not find associate anomalies significant or for an
      inadequate valuation of the hemodynamic repercussion. The surgery drifted based
      on the study echocardiography had to modify in 14% of the total of the group,
      none of the patients died. The cardiopathy where there was repercussion in the
      outlined surgical handling they were: aortopulmonar window, stenosis of lung
      veins, anomalous connection of lung veins, anomalies of coronary arteries. The
      echocardiogram is the angular stone where it rests the diagnosis of the
      congenital heart defect, the obtained information and its accuracy will be bigger
      as soon as adult is the clinical support.

PMID- 17017092
TI  - [Physiopathogenesis of hypertension].
AB  - Arterial hypertension is one of major cardiovascular risk factors in the world.
      Many pathophysiologic factors have been implicated in the genesis of hypertension
      such as increased sympathetic nervous system activity, overproduction of sodium
      retaining hormones and vasoconstrictors, increased or inappropriate renin
      secretion with resultant increased production of angiotensin II and aldosterone,
      deficiencies of vasodilators, vascular reactivity, vascular remodeling,
      production of inflammatory molecules and endothelial dysfunction. On the other
      hand, the hereditary nature of this disease has been well established in many
      familial studies The quantitative contribution of genetic factors to blood
      pressure variance is estimated to be about 30%.

PMID- 17017093
TI  - [Salt-sensitive hypertension].
AB  - Individuals with elevated blood pressure are at increased risk for cardiovascular
      events and death. Almost 50% of essential hypertension is salt-sensitive, this
      characteristic increases and becomes more prevalent with age. Salt sensitivity
      has been linked to an increased risk for the development of left ventricular
      hypertrophy, proteinuria, and a blunted nocturnal decline in blood pressure ("non
      dipping"). Salt sensitivity implies an alteration in the relation between
      arterial pressure and sodium excretion or "pressure natriuresis". The development
      of salt-sensitive hypertension is proposed to occur in three phases. In the first
      phase, the kidney is structurally normal, and sodium is excreted normally.
      However, the kidney may be exposed to various stimuli that result in renal
      vasoconstriction. In the second phase, subtle renal injury develops, impairing
      sodium excretion and leading to an increase in blood pressure. In the third
      phase, the kidneys equilibrate at a higher blood pressure, allowing them to
      resume normal sodium handling. Other mechanisms, such as primary
      tubulointerstitial disease, genetic alterations in sodium regulation and
      excretion, or a congenital reduction in nephron number that limits sodium
      filtration are important in the development of salt-sensitive hypertension.

PMID- 17017094
TI  - [Endothelial function].
AB  - The endothelium is the first line of tissue whose function is affected by the
      cardiovascular risk factors. The normal function of this vascular covering
      maintains the homeostasis of the vascular bed and its alterations favors the
      appearance of the initial lesions of various diseases including the
      atherosclerotic process. The endothelial function can be measured by means of non
      invasive methods and these measures can identify the people at higher risk to
      develop atherosclerosis and its complications and also the methodology has proven
      to be useful in the evaluation of the outcomes related to the therapeutic
      measures. The possibility of performing this methods in a safe, non invasive and
      reproducible way permits that the endothelial function could be used as screening
      tool for cardiovascular risk in open population.

PMID- 17017095
TI  - [Molecular aspect of systemic arterial hypertension].
AB  - Some genetic issues of hypertensive diseases are discussed, as well as some
      benefits of the study of these aspects in the clinical management of high blood
      pressure. Some characteristics of hypertension as a "civilization disease" are
      pointed out, particularly the combination of pathogenic genetic and environmental
      mechanisms. Interactions among genes and environment are described as well as
      rare examples of monogenic hypertension. Some genes with hypertensive action
      potential are mentioned. It is difficult to establish the connection among the
      polymorphisms and the development of hypertension or its complications and
      consequences. It is underlined the urgent need to establish the true importance
      of these already known polymorphisms, and other still undisclosed, in the Mexican
      population.

PMID- 17017096
TI  - [Cardiovascular risk stratification].
AB  - In often cited statistic cardiovascular disease is the number 1 cause of death in
      the worldwide and not only in the developed world. This represents an aggressive
      identification and management of risk factors. With the many advances in our
      understanding and practices of risk factor management we hope to change this
      tendency predicted to be in 2020 the same. Now we know that exists major factor
      risk and others who predispose. The presence of major risk factors was associated
      with development of cardiovascular disease. The process of risk factor management
      is a multidisciplinary one, directly involving both the patient his doctor as
      well as many others, including nurses, other healthcare and family. The goal is
      preventing future cardiac events.

PMID- 17017097
TI  - [Pathophysiology of heart failure].
AB  - Treatment of heart failure has been successfully target biologically, to
      counteract deleterious effects resulting from neuroendocrine activation, with the
      use of several agents (e.g., angiotensine-converting enzyme inhibitors, beta
      adrenergic receptor blockers, spironolactone), that provide benefical effects,
      demonstrated in multicentric trials in controlled populations. However, this mid
      term benefit, becomes less effective with time, resulting in progression of the
      disease to terminal stages and death. The purpose of this paper is to review
      other pathophysiologic pathways and the potential application of preventive
      measures to be incorporated in the standardized treatment of heart failure.

PMID- 17017098
TI  - [Biventricular resynchronization in the treatment of chronic heart failure].
AB  - Chronic heart failure (CHF) caused by systolic dysfunction is a disease of
      epidemic proportions. Although pharmacological therapy has ameliorated symptoms
      and improved the survival of these patients, this chronic syndrome remains a
      progressive disease, causing incremental morbidity and early mortality.
      Preliminary studies show that ventricular resynchronization significantly
      improves exercise tolerance and the quality of life in patients with CHF who have
      sinus rhythm and major intraventricular conduction delay. Cardiac
      resynchronization therapy requires in synchrony with atrial activity.
      Atriobiventricular pacing significantly improved symptoms, exercise tolerance and
      the quality of life. The use of this procedure today should be individualized
      however, further studies are needed to assess the long-term clinical effect of
      this therapeutic approach.

PMID- 17017099
TI  - [Atrial fibrillation: rhythm vs. rate control].
AB  - The atrial fibrillation treatment has been controversial since almost a century.
      Several studies have been done and there is not a clear therapeutic strategy
      despite the new technological advances. The disyuntive persist between sinus
      rhythm control vs. ventricular rate control. The main studies like AFFIRM, RACE,
      PIAF, PAF2 and STAF have not shown a definitive strategy treatment. Recently,
      several subgroups have been stablished and variables like life quality and
      functional state have been included. New therapeutic strategies have resulted.
      Heart rate control is recommendable for asymptomatic 65 years old patients and
      older, whereas rhythm control is better for patients with severe symptoms.

PMID- 17017101
TI  - [Surgical treatment of atrial fibrillation associated with mitral valve disease].
AB  - The modified Cox maze procedure is the gold standard for ablation of atrial
      fibrillation in patients undergoing mitral valve surgery, and new approaches to
      atrial fibrillation ablation must be compared with it. Therefore, we sought to
      determine the time-related prevalence of atrial fibrillation and its risk factors
      after combined Cox maze and mitral valve surgery. In some patients undergoing
      mitral valve surgery and a Cox maze procedure, atrial fibrillation recurs over
      time, mandating close, long-term follow-up of heart rhythm. Earlier operation
      should be considered to improve results in selected patients.

PMID- 17017100
TI  - [Electroanatomic mapping system (CARTO) to perform catheter ablation of atrial
      fibrillation].
AB  - Since the first report of radiofrequency catheter ablation curing atrial
      fibrillation (AF) nearly a decade ago, numerous techniques have evolved, from
      linear ablation to modify the reentrant sustrate for AF, to electrical isolation
      of pulmonary vein to eliminate triggers of AF, to hibrid approaches of
      circunferential ablation around and between the pulmonary veins and mitral valve
      annulus to modify both the triggers and sustrate for AF. We describe the
      electroanatomic mapping system (CARTO, Biosense Webster) and its use in patients
      undergoing catheter ablation for AF.

PMID- 17017102
TI  - [Evidence-based treatment of atrial fibrillation].
AB  - Radiofrequency catheter ablation has emerged as a curative therapy for paroxysmal
      atrial fibrillation based on studies demonstrating the role of triggering foci in
      the pulmonary veins for the initiation of atrial fibrillation. Catheter ablation
      is performed by a trans-septal approach using radiofrequency energy at the ostium
      of each pulmonary vein. Mapping is guided by special catheters. Sequential
      radiofrequency applications eliminates or dissociates pulmonary vein muscle
      activity. Although complications exists, this procedure can be curative for these
      patients.

PMID- 17017103
TI  - [Clinical indications for implant of CID in patients with coronary heart disease
      and cardiac failure].
AB  - The mortality of the myocardial acute infarction has diminished with the
      introduction of the new strategies of reperfusion; this way, the number of
      patients with ventricular left dysfunction has increased. This one is a special
      population with risk greater than rest of people of suffering an event of cardiac
      sudden death (SD). This fact needs of a suitable process of stratification of the
      risk for SD that this population has and it is necessary measures of primary and
      secondary prevention to diminish the mortality of these patients. In this paper
      the clinical characteristics of this population by precedent of heart attack of
      the myocardium and/or ventricular left dysfunction are checked. These characters
      can suggest the indication for the implant of an automatic defibrillator.

PMID- 17017104
TI  - [Dual chamber pacemakers: common problems and how to treat them].
AB  - In the last ten years the technology in Electrophysiology and Cardiac Parcing has
      advanced rapidly until the arrive of the implantable cardioverter defibrillator
      for the prevention of Sudden Death and also to the three chamber pacing for
      ventricular resinchronization as a treatment for advanced heart failure. In the
      middle of these we have dual chamber pacemakers. The increasing expectative of
      life worldwide gives the need and more frequency of implanting dual chamber
      pacemakers with the exception of the patient with chronic atrial fibrillation.
      For these reasons, it is important not only to detect the common problems of the
      dual chamber pacemakers but how to treat them. In this review we will define
      pacemaker pseudomalfunction: the identification of fusion and pseudofusion beats;
      the normal pacemaker functions that could be confused with malfunction. About
      malfunction it will be described the causes and the way for treating oversensing,
      undersensing, loss of capture, loss of output; how to identify and to treat
      pacemaker reset, myopotentials stimulation, pacemaker syndrome and finally
      pacemaker-mediated tachycardia.

PMID- 17017105
TI  - [Cardiac stimulations for the treatment of supraventricular arrhythmias].
AB  - Permanent cardiac stimulation in patients with supraventricular tachycardia is
      used primary for treatment and prevention of atrial fibrillation (AF). Different
      strategies of stimulation have been design for this purpose. Among the most
      important are: preferential standard atrial pacing, multisite atrial pacing or
      septal atrial pacing and pacing algorithms for prevention or treatment.
      Multicentric, controlled and randomized studies design to explore this therapies
      have disappointing and controversial results. Current therapy is focused in the
      implant of physiological pacemakers (AAI, DDD) rather than VVI pacemakers. Right
      apical ventricular stimulation has deleterious effects in ventricular function by
      producing a dissincronous ventricular contraction and increasing the incidence of
      AF, so ventricular pacing must be avoided in patients with intact
      atrioventricular conduction. CONCLUSION: Permanent cardiac pacing in patients
      without symptomatic bradycardia should not be used to treat supraventricular
      tachycardias. Physiologic pacing should be used to reduce the incidence of AF.
      Effort should be made to allow normal atrioventricular conduction in patients
      with sick sinus disease and normal atrioventricular conduction.

PMID- 17017106
TI  - [Permanent cardiac pacing in vasovagal syncope: when and which?].
AB  - Vasovagal syncope is a common clinical problem forming the pathophysiological
      basis of half the cases of syncope. Although it usually has a favourable
      prognosis, it may be a highly limiting clinical problem in a particular subset of
      patients among whom syncopal recurrences are frequent and without prodromic
      symptoms, or have a traumatic outcome. For this subgroup of patients the term
      "malignant vasovagal syncope" has been proposed. The treatment of these highly
      symptomatic patients is necessary to avoid dangerous injuries and to improve the
      quality of life. Pacemaker therapy has been advocated as a potential therapy in
      severe or drug refractory cases. This paper reviews the concepts behind pacemaker
      therapy for vasovagal syncope and the results of various clinical trials that
      have evaluated its potential utility as a primary therapeutic modality.

PMID- 17017107
TI  - [Vulnerable plaque actual and future identification methods].
AB  - The atherothromboses is the principal cause of death in the western World, the
      rupture of the vulnerable plaque is the trigger of the acute coronary syndromes.
      The importance of identifying the vulnerable plaque before its rupture continues
      being a challenge. At the moment the diagnosis can be made by noninvasive
      methods, like the presence of risk factors and blood markers of vulnerability and
      invasive methods like angiocospic. Although several methods exist, there is no
      one that gives all morphologic and inflammatory activity; it seems that the
      thermography is going to be the most helpful. The future will be not just the
      diagnosis of vulnerable plaque but the vulnerable patient.

PMID- 17017108
TI  - [From thrombin hypothesis to inflammation. Is it reality?].
AB  - The classical pathophysiologic concept of the acute coronary syndromes is the
      coronary artery thrombosis as a consequence of rupture or vulnerable
      atherosclerotic plaques. Actually, it is also been considered that systemic
      inflammatory phenomenon play a central role in the plaque instability associated
      to the atherothrombotic activity of the tissue factor (TF). The thrombotic
      phenomenon is controlled by tissue factor, stimulating the way of the protease's
      active receptors (PAR) and cause a negative cycle between inflammation and
      coagulation.

PMID- 17017109
TI  - [From the single vulnerable plaque, to the multiple complex coronary plaques.
      From their basis, to the modern therapeutic approach. A clinical reality in the
      spectrum of the acute coronary syndromes].
AB  - Contemporary clinical and laboratory data have challenged our classical concepts
      of the pathogenesis of the acute coronary syndromes [ACS]. Indeed, several
      independent lines of clinical evidence have supported that the critical stenoses
      cause only a fraction of the ACS. Acute myocardial infarction is believed to be
      caused by rupture of a vulnerable coronary-artery plaque that appears as a single
      lesion on angiography. However, plaque instability might be caused by
      pathophysiologic processes, such as inflammation, that exert adverse effects
      throughout the coronary vasculature and therefore result in multiple unstable
      lesions. Recent studies have demonstrated that ruptured or vulnerable plaques
      exist not only at the culprit lesion but also in the whole coronary artery in
      some ACS patients. It has also been reported that a ruptured plaque at the
      culprit lesion is associated with elevated C- reactive protein and other
      inflammatory markers, which indeed indicate a poor prognosis in patients with
      ACS. Also, multiple plaque rupture is associated with systemic inflammation, and
      patients with multiple plaque rupture can be expected to show a poor prognosis.
      Therefore some ACS patients [20-40%] may harbor multiple complex coronary plaques
      that are associated with adverse clinical outcomes. It should be accepted that
      this ACS population represent a part of the spectrum of the ACS, and in
      particular in this group of patients treatment should focus not only on the
      stabilization of the culprit site but also warrants a broader approach to
      systemic stabilization of the arteries. However, recurrent cardiovascular events
      in this population still remain unacceptably high, indicating that plaque rupture
      or vulnerability of multiple plaques is a current challenge in the management of
      ACS patients.

PMID- 17017110
TI  - [Risk marker stratification in coronary acute syndromes].
AB  - Acute coronary syndromes have a heterogeneous clinical presentation with a broad
      spectrum for mortality and adverse events. It is mandatory to identify high risk
      groups for percutaneous coronary intervention and intensive antithrombotic
      treatment or common risk for standard treatment. In contemporaneous medicine it
      is important to get adequate risk stratification because the impact of
      hospitalary costs, antithrombotic and reperfusion treatment on health systems.
      The current pathophysiology of atherosclerosis is moving from a disease secondary
      to cholesterol deposit, to an inflammatory disease. In the stratification
      process, familiar history, chest pain, ST dynamic abnormalities, left ventricular
      wall motion abnormalities, all have predictive value. The association of indirect
      endothelial dysfunction, micro or macronecrosis and ventricular dysfunction
      markers increase this value. In our experience a close relationship among
      abnormal fibrinolysis, inflammation and anticoagulation proteins with adverse
      events has been proved in acute coronary syndromes. Other interesting finding-
      for it accessibility--in acute myocardial infarction under coronary percutaneous
      intervention is persistent ST elevation, leukocytes and fibrinogen predictive
      value. In population allelic polymorphisms -455A and -148T and fibrinogen ( >450
      mg/dL) were associated with coronary disease. These polymorphisms improve risk
      stratification of coronary disease to establish a better secondary prevention and
      treatment.

PMID- 17017111
TI  - [Acute coronary ischemic syndrome without ST elevation. Role of glycoprotein
      IIB/IIIA inhibitors and percutaneous coronary interventions].
AB  - Myocardial infarction without ST elevation and unstable angina, represents a
      diagnostic challenge. This Syndromes are caused by rupture of a vulnerable plaque
      which determines intraluminal thrombosis, distal embolism and coronary
      obstruction. Administration of IIb/IIIa inhibitors produces some benefits, mainly
      in those patients who are taking to catheterization. Coronary intervention based
      on a routine invasive strategy, has decreased major cardiac events principally at
      long term.

PMID- 17017112
TI  - [ST elevation acute coronary syndromes. Pharmaco-mechanic strategy is the
      universal treatment future?].
AB  - The main objective in the medical treatment of the ST elevation acute myocardial
      infarction, must have the intention to reperfuse the culprit involved artery. In
      order to reduce this time, the pharmaco-invasive strategy may offer rapid flow
      recanalization in the culprit artery and reduce the damage of the myocardium. The
      new pharmacologic combinations includes half dose of fibrinolytics, alone or in
      combination with IIb/IIIa inhibitors, this combination may offer advantages of
      the flow. This concept involves the that PCI (Percutaneous Coronary
      Interventions), can be done in a subsequent time. The risk of bleeding is
      increased with this strategy, and some evaluation or bleeding risk must be done
      in all patients, as in patients with 75 years and older.

PMID- 17017113
TI  - [Recent considerations of cardiogenic shock associated to the acute coronary
      ischemic syndromes].
AB  - We review novel physiopathological concept of Cardiogenic Shock associated to
      acute coronary ischemic syndromes, where the mechanist terms become jumbled not
      only, but the neuro-hormonal, immuno-inflammatory, and biomolecular alterations.
      In order to offer a pharmacointensive treatment that obtains the stabilization of
      the acute coronary Syndrome, for the reduction of myocardial ischemia. Also, we
      incorporate the incidence of this pathology in the Mexican population.

PMID- 17017114
TI  - [Clinical stratification of cardiogenic shock].
AB  - Cardiogenic shock (CHC) associated to acute myocardial infarct has high mortality
      and their manifestations are heterogenous. In our institution historical
      mortality, was 98%, but with different methods of reperfusion, its reduced to
      53%. In other hand, with opportune clinical stratification is useful to improve
      the treatment strategy. This stratification on basis in clinical signs: age,
      infarction location, cardiac frequency and systemic arterial pressure, and
      hemodynamical valuation with the use of right catheterism with quantification
      miocardial work parameters like "Cardiac power" that is the product of flow and
      arterial pressure and that is of utility to know the "Miocardial reserve". In our
      experience after reperfusion procedure patients with CHC and cardiac power less
      than 1.0 had highly mortality.

PMID- 17017115
TI  - [Cardiogenic shock: treatment of the near future].
AB  - The mortality rate for cardiogenic shock has decreased over the past decade.
      These improvements are presumed to reflect increased use of intraaortic ballon
      counterpulsation and coronary reperfusion strategies which, by restoring patency
      to the infarct-related artery, can limit infarct size. Despite these therapeutic
      measures, mortality rates remain elevated. Current strategies are aimed at
      decreasing reperfusion times and measures to preserve and prolong myocardial cell
      viability.

PMID- 17017116
TI  - [Cardiogenic shock continues to be the most serious complication of the acute
      myocardial infarction].
AB  - The actual therapeutic guidelines, look to conceive reperfusion of the infarcted
      myocardial areas in less time with pharmacological treatment, interventionist
      procedures or surgery for revascularization. CABG should be consider as a
      therapeutic modality that can be use for the treatment of cardiogenic shock, in
      well selected patients, as in those who primary angioplasty could not be achieved
      as treatment for the acute myocardial infarction. We revised the patients
      characteristics, the useful modalities and benefits that CABG can offer in this
      pathology.

PMID- 17017117
TI  - [Guidelines of the National Institute of Cardiology "Ignacio Chavez" for the
      treatment of systemic arterial hypertension].
AB  - The arterial hypertension in Mexico has a prevalence of 30%, with some
      differences in the geographical distribution. Of this population two relevant
      aspects are outlined: the high prevalence of arterial hypertension in young
      people and the common association with other factors of cardiovascular risk.
      Associated with these facts, it is of be making notice that an important
      percentage of this people doesn't know the diagnosis, and that those who have
      this diagnosis established often does not receive treatment or, has an evil
      control of the value of the arterial tension them in spite of receiving
      pharmacological treatment. The guidelines for the treatment of the arterial
      hypertension in our country are based on anatomic characteristics proper of our
      population, and they are based in a process of risk stratification elaborated
      with the same characteristics. These guidelines are the recommendations for the
      initial treatment of the arterial hypertension but must be remembered the
      fundamental concept of the medicine that establishes that any treatment must be
      completely individualized.

PMID- 17017118
TI  - Joint Commission to launch data management tool in 2007.

PMID- 17017119
TI  - Approved: revisions to the public information policy.

PMID- 17017120
TI  - Long term care accreditation program celebrates its 40th anniversary.

PMID- 17017121
TI  - Arginine to cysteine mutation (R499C) found in a Japanese patient with complete
      myeloperoxidase deficiency.
AB  - Animal models suggest that a deficiency in myeloperoxidase (MPO; EC 1.11.1.7), a
      lysosomal hemoprotein involved in host defense, may be associated with a
      decreased level of immunity. A nonsynonymous mutation, resulting in an arginine
      to cysteine substitution (Arg499Cys or R499C), has been identified in the exon 9
      genetic coding region of a Japanese patient with complete MPO deficiency. Genetic
      analysis revealed that the mRNA of the patient could be correctly transcribed
      then further translated into a peptide sequence. However, the Western blot
      analysis confirmed the absence of MPO peptides. An initial screening assay of the
      patient's blood exhibited an abnormal hematograph, and no MPO activity was
      detected. To determine if this mutation might be associated with MPO deficiency,
      DNA samples for 387 controls were examined. Genetic analysis was performed using
      standard PCR techniques for amplification and sequencing. None of the control
      samples possessed the R499C substitution. This mutation is in close proximity to
      a different mutation (G501S) previously found in another Japanese MPO-deficient
      patient, and the amino acid, H502, which is strongly involved in heme binding,
      leading to the speculation that heme binding may play a role in complete MPO
      deficiency.

PMID- 17017122
TI  - PKCdelta alternatively spliced isoforms modulate cellular apoptosis in retinoic
      acid-induced differentiation of human NT2 cells and mouse embryonic stem cells.
AB  - NT2 cells are a human teratocarcinoma cell line that, upon treatment with
      retinoic acid (RA), begin differentiating into a neuronal phenotype. The
      transformation of undifferentiated NT2 cells into hNT neurons presents an
      opportunity to investigate the mechanisms involved in neurogenesis because a key
      component is cell apoptosis, which is essential for building neural networks.
      Protein kinase Cdelta (PKCdelta) plays an important role as a mediator of
      cellular apoptosis in response to various stimuli. PKCdelta (deltaI) is
      proteolytically cleaved at its hinge region (V3) by caspase 3 and the catalytic
      fragment is sufficient to induce apoptosis in various cell types. Mouse
      PKCdeltaII is rendered caspase resistant due to an insertion of 78 bp within the
      caspase recognition site in its V3 domain. No functional role has been attributed
      to these alternatively spliced variants of PKCdelta. We sought to find a
      correlation between the onset of apoptosis, neurogenesis, and the expression of
      PKCdelta isoforms. Our results indicate that RA regulates the expression of
      PKCdelta alternative splicing variants in NT2 cells. Further, overexpression of
      PKCdeltaI promotes apoptosis while PKCdeltaII overexpression shields the cells
      from apoptosis. This is the first report to attribute physiological function to
      PKCdeltaI and -deltaII isoforms. Next we demonstrated that mouse embryonic stem
      cells differentiate in vitro into dopaminergic neurons upon stimulation with RA
      and ciliary neurotrophic factor. These cells showed a simultaneous increase in
      tyrosine hydroxylase and PKCdeltaII expression. We suggest that the molecular
      mechanisms regulating differentiation and apoptosis could be understood by
      alternative expression of PKCdelta isoforms.

PMID- 17017123
TI  - Transcriptional profiling of the cell cycle checkpoint gene kruppel-like factor 4
      reveals a global inhibitory function in macromolecular biosynthesis.
AB  - Kruppel-like factor 4 (KLF4; also known as gut-enriched Kruppel-like factor or
      GKLF) is known to exhibit checkpoint function during the G1/S and G2/M
      transitions of the cell cycle. The mechanism by which KLF4 exerts these effects
      is not fully established. Here we investigated the expression profile of KLF4 in
      an inducible system over a time course of 24 h. Using oligonucleotide
      microarrays, we determined that the fold changes relative to control in
      expression levels of KLF4 exhibited a time-dependent increase from 3- to 20-fold
      between 4 and 24 h following KLF4 induction. During this period and among a group
      of 473 cell cycle regulatory genes examined, 96 were positively correlated and 86
      were negatively correlated to KLF4's expression profile. Examples of upregulated
      cell cycle genes include those encoding tumor suppressors such as MCC and FHIT,
      and cell cycle inhibitors such as CHES1 and CHEK1. Examples of downregulated
      genes include those that promote the cell cycle including several cyclins and
      those required for DNA replication. Unexpectedly, several groups of genes
      involved in macromolecular synthesis, including protein biosynthesis,
      transcription, and cholesterol biosynthesis, were also significantly inhibited by
      KLF4. Thus, KLF4 exerts a global inhibitory effect on macromolecular biosynthesis
      that is beyond its established role as a cell cycle inhibitor.

PMID- 17017124
TI  - Inhibition of translation by consecutive rare leucine codons in E. coli: absence
      of effect of varying mRNA stability.
AB  - Consecutive homologous codons that are rarely used in E. coli are known to
      inhibit translation to varying degrees. As few as two consecutive rare arginine
      codons exhibit a profound inhibition of translation when they are located in the
      5' portion of a gene in E. coli. We have previously shown that nine consecutive
      rare CUA leucine codons cause almost complete inhibition of translation when they
      are placed after the 13th codon of a test message (although they do not inhibit
      translation when they are placed in the middle of the message). In the present
      work, we report that five consecutive rare CUA leucine codons exhibit
      approximately a threefold inhibition of translation when they are similarly
      placed after the 13th codon of a test message, compared to five consecutive
      common CUG leucine codons, in a T7 RNA polymerase-driven system. Further, by
      removing RNase III processing sites at the 3' ends of the mRNAs, we have
      manipulated the stability of the mRNAs encoding the test and control messages to
      see if decreasing mRNA stability might have an effect on the extent of
      translation inhibition by the rare leucine codons. However, the inhibition with
      the less stable mRNAs was similar to that with the stable mRNAs, approximately
      3.4-fold, indicating that mRNA stability per se does not have a major influence
      on the effects of rare codons in this system.

PMID- 17017125
TI  - Global gene expression profiling of dimethylnitrosamine-induced liver fibrosis:
      from pathological and biochemical data to microarray analysis.
AB  - The development of hepatocellular carcinoma (HCC) is generally preceded by
      cirrhosis, which occurs at the end stage of fibrosis. This is a common and
      potentially lethal problem of chronic liver disease in Asia. The development of
      microarrays permits us to monitor transcriptomes on a genome-wide scale; this has
      dramatically speeded up a comprehensive understanding of the disease process.
      Here we used dimethylnitrosamine (DMN), a nongenotoxic hepatotoxin, to induce rat
      necroinflammatory and hepatic fibrosis. During the 6-week time course,
      histopathological, biochemical, and quantitative RT-PCR analyses confirmed the
      incidence of necroinflammatory and hepatic fibrosis in this established rat model
      system. Using the Affymetrix microarray chip, 256 differentially expressed genes
      were identified from the liver injury samples. Hierarchical clustering of gene
      expression using a gene ontology database allowed the identification of several
      stage-specific characters and functionally related clusters that encode proteins
      related to metabolism, cell growth/maintenance, and response to external
      challenge. Among these genes, we classified 44 potential necroinflammatory
      related genes and 62 potential fibrosis-related markers or drug targets based on
      histopathological scores. We also compared the results with other data on well
      known markers and various other microarray datasets that are available. In
      conclusion, we believe that the molecular picture of necroinflammatory and
      hepatic fibrosis from this study may provide novel biological insights into the
      development of early liver damage molecular classifiers than can be used for
      basic research and in clinical applications. A public accessible website is
      available at http://LiverFibrosis.nchc.org.tw:8080/LF.

PMID- 17017126
TI  - Cholinergic differentiation occurs early in mouse sympathetic neurons and
      requires Phox2b.
AB  - The generation of neurotransmitter identity in the autonomic nervous system is a
      classical model system to study the development of neuronal diversity. Analysis
      of the expression of genes coding for enzymes of noradrenaline biosynthesis in
      the sympathoadrenal system allowed the characterization of factors involved in
      the differentiation of the noradrenergic transmitter phenotype. The development
      of cholinergic properties in the autonomic system is less well understood. Here
      we show that expression of mRNAs for choline acetyltransferase (ChAT) and the
      vesicular acetylcholine transporter (VAChT), both encoded by the cholinergic gene
      locus, is induced in mouse sympathetic ganglia at embryonic day 11 (E11).
      Positive cells amount to more than 50% of Phox2b-positive sympathetic cells at
      cervical levels. The proportion declines caudally, decreasing to approximately
      20% of Phox2b-positive cells at lower thoracic levels. In the adrenal anlage,
      ChAT and VAChT mRNA are largely undetectable at E11 and E13. In mice homozygous
      for a mutational inactivation of the transcription factor Phox2b, ChAT and VAChT
      mRNA expression is absent from sympathetic ganglia. The data show that expression
      from the cholinergic gene locus is regulated differently in sympathetic neurons
      and adrenal chromaffin cells. Phox2b is required for development of cholinergic
      neurons but does not suffice to support cholinergic properties in chromaffin
      cells.

PMID- 17017127
TI  - Importance of considering injured microorganisms in sterilization validation.
AB  - Disinfection or sterilization treatment by heating, irradiation, or chemicals can
      cause injury to microorganisms at sublethal levels. Microbial injury is the
      inability to grow under conditions suitable for the uninjured microorganisms.
      This inability of injured microorganisms to grow is explained in terms of more
      complex or different nutritional requirements or in terms of increased
      sensitivity to environmental conditions such as incubation conditions (time or
      temperature) or to chemical agents such as halogen compounds. Injured
      microorganisms can be distinguished from those that are dead or mutated by their
      ability to regain normal physiological activity when placed in appropriate
      conditions for cultivation. The return to normal physiological function has been
      termed repair. The extent and severity of sublethal injury, the mechanisms of
      injury, and the mechanisms and degree of recovery vary with the sterilization
      procedures, the species, the strains, the condition of the microorganism, and the
      methods of repair. Injury to spore formers has been detected at different stages
      of the spore cycle. The sites of injury include damage to enzymes, membrane
      disruption, and/or damage to DNA or RNA. Information on the sublethal injury and
      recovery of microorganisms is very important in evaluating
      sterilization/disinfection procedures. This paper supplies academic as well as
      practical information dealing with the repair, and detection of injured
      microorganisms for performing reproducible sterilization validation.

PMID- 17017128
TI  - Construction of a leftover bath water model for microbial testing.
AB  - In this study, in order to construct a model of leftover bath water, we analyzed
      one hundred samples of used bath water samples which were provided by twenty
      eight volunteer families. It appeared that the number of detected bacteria from
      such bath water was correlated closely with the number of bathers. Moreover, the
      pH, acidity, chemical oxygen demand (COD), ion, protein content of the leftover
      bath water were measured. The number of bathers had no connection with the pH,
      acidity, COD, and ion content of the leftover bath water. However, the protein
      content of the bath water correlated with the number of detected bacteria. Based
      on these results, the model of leftover bath water was constructed. Achromobacter
      xylosoxidans, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia
      coli, Klebsiella pneumoniae, Pseudomonas aeruginosa were incubated with the model
      bath water as indices of bath water contamination. The number of incubated viable
      cells in the model bath water increased with increasing concentrations of
      casamino acid. Consequently, it was suggested that varying the concentration of
      casamino acid based on family size or contamination would be necessary in the
      efficient use of the constructed model of leftover bath water for microbial
      testing.

PMID- 17017129
TI  - Correlation between the bacterioclastic action of a bis-quaternary ammonium
      compound and outer membrane proteins.
AB  - Bis-quaternary ammonium compounds (bis-QACs) have the ability to cause a rapid
      and abundant leakage of the turbid materials from cells, and such a
      bacterioclastic ability leads to a potent bactericidal activity. In order to
      clarify the detailed mechanism of the bactericidal action of bis-QACs, the
      correlation between the bacterioclastic action of 4,4'-(1,6
      hexamethylenedithio)bis(1-octylpyridinium bromide) (4DTBP-6,8) and the leakage of
      outer membrane pore protein E (OmpE) was investigated. Using the antiserum
      against a fusion protein consisting of GST and the OmpE protein of Escherichia
      coli encoded by the ompE gene, it was seen that the leakage of OmpE from E. coli
      cells was caused by treatment with low concentrations (much lower than the
      critical vesiculation concentration) of 4DTBP-6,8. Furthermore, it was confirmed
      that 4DTBP-6,8 caused an increase in the turbidity of the cell suspension of
      Klebsiella pneumoniae, Salmonella typhimurium and Serratia marcescences, and led
      to the leakage of several proteins which have a high percentage of homology with
      OmpE of E. coll. By immunoelectron microscopy investigation, it was revealed that
      the vesiculation from E. coli treated with 4DTBP-6,8 contains OmpE. In addition,
      the bacteriolytic action of 4DTBP-6,8 was investigated. The results suggested
      that the lysis of cells by bis-QACs was not an enzymatic action such as that by
      autolysin but a physical bacterioclastic action. Judging from these results, it
      is suggested that the leakage of OmpE is one of the major bacterioclastic actions
      of bis-QACs, and deals the bacterial cells a fatal blow.

PMID- 17017130
TI  - Kinetic analysis of the antifungal activity of heated scallop-shell powder
      against Trichophyton and its possible application to the treatment of
      dermatophytosis.
AB  - The antifungal activity of scallop-shell powder heated at 1000 degrees C for 1 h
      against Trichophyton was kinetically investigated and the possibility of applying
      the powder to the treatment of dermatophytosis was examined. The death rate of T.
      mentagrophytes NBRC5466 in the heated shell powder slurry increased with powder
      concentration, following first-order reaction kinetics. Elevated slurry
      temperatures increased both the apparent first-order death rate constant (k) and
      the dilution coefficient (n) representing the dependence of k on reagent
      concentration. The activation energy for the death of NBRC5466 was almost equal
      to that for bacteria, whereas the n value was much smaller than that for
      bacteria. In addition, the trial using heated shell powder treatment on feet
      showed the possibility of its application to treat dermatophytosis.

PMID- 17017131
TI  - Detection of Listeria monocytogenes from food samples by PCR after IMS-plating.
AB  - For rapid, accurate and sensitive detection of Listeria monocytogenes in food
      samples, colonies developed on the selective agar (Oxford agar) after
      immunomagnetic separation (IMS) were subjected to polymerase chain reaction (PCR)
      assay with the prf A1-2 primer pair. The proposed assay system was shown
      experimentally to be capable of specifically detecting the bacteria from food
      samples contaminated at more than 10(2) cfu/g. However, the enrichment culture
      after a short period of 16 h with the appropriate selective broth was needed
      before IMS-plating, because the bacterial contents in most actual food were as
      low as less than 10(2) cfu/g. However, even if the enrichment cultivation was
      employed before IMS, L. monocytogenes was detected within 3 days.

PMID- 17017132
TI  - Background and evidence leading to the establishment of the JIS standard for
      antimicrobial products.
AB  - This article describes the circumstances involved in the standardization of the
      evaluation methods for antimicrobial products. The quantitative method of JIS L
      1902 was adopted as the test method for textile products. For plastic, metal and
      ceramic products, examination of test methods proceeded through the investigation
      of references and reference to test methods used by various industrial
      organizations, and a new test method was developed based on the film covering
      method. An evaluation standard for antimicrobial efficacy was also set up for
      these test methods and was established as a JIS standard (JIS Z 2801:2000).

PMID- 17017133
TI  - [Reconstruction of nasal defects using a reverse preauricular flap by
      microsurgical technique].
AB  - OBJECTIVE: This article reports the design and application of a free reverse
      preauricular flap for one-stage reconstruction of nasal defects. METHODS: A
      preauricular flap was designed according to the nasal defect, which was harvested
      with the reverse superficial temporal vessels as its vascular pedicle. The flap
      size ranged from 3.0 cm x 2.5 cm to 6 cm x 2 cm without any hair-bearing skin. In
      flap transferring, its pedicle of the superficial temporal vessels was
      anastomosed with the facial vessels in the nasolabial fold. RESULTS: The flap
      survived uneventfully in these three patients. The defects in the distal nose
      were reconstructed with satisfactory results. The donor site scar was similar to
      that of face-lift incision. CONCLUSIONS: This is the first report of clinical
      applications of the free reverse preauricular flap by microsurgical technique.
      Microsurgical technique allows successful transfer of this flap in a one-stage
      procedure. Because of its similar color and texture to the facial skin, this flap
      provides excellent tissues for coverage of the nasal defect. This technique may
      have even wider applications for other facial cutaneous defects.

PMID- 17017134
TI  - [The lateral crural flap nourished by cutaneous branches of peroneal artery: an
      anatomic and clinical study].
AB  - OBJECTIVE: To study the anatomy of lateral crural skin flap nourished by
      cutaneous branches of peroneal artery and its clinical application as
      vascularized skin flap transfer. METHODS: In 20 cadavers specimen with 40 lower
      limbs, the cutaneous branches of the peroneal artery were dissected and their
      measurements were recorded. In the other 30 adult legs, their perforating points
      of the cutaneous arteries of peroneal artery were detected with supersonic
      Doppler flow meter. With the aid of anatomic and supersonic Doppler flow meter
      study, vascularized transfer of lateral crural skin flap pedicled by cutaneous
      branches of peroneal artery were successfully performed in 21 clinical cases.
      RESULTS: In altogether 40 legs studied, 140 cutaneous branches were found. One to
      seven branches were found on one specimen, the average was 3.5 branches, in one
      leg was a high perforating skin branch. The perforating points of the cutaneous
      branches were mostly (76% cases) appeared within 7 - 21 cm length below the
      protruding point of head of fibula. The external diameter of the thickest
      cutaneous branch of each leg was (1 .4 - 2.9) mm, (1.8 +/- 0.4) mm, while the
      external diameters of two vena concomitants were (3.0 +/- 0.5) mm and (2.4 +/-
      0.4) mm. 145 artery perforating points in 30 legs were detected by Doppler, with
      an average points of 4.8. The skin flaps taken in the 21 clinical cases were 5.0
      cm x 3.5 cm - 28 cm x 11 cm in size. All the transferred free flaps survived
      uneventfully. CONCLUSIONS: The lateral crural skin flap is nourished by a
      variable number of cutaneous branches of peroneal artery. The main branch can
      meet the demand of microvascular anastomosis. The free transfer of lateral crural
      flap by anastomosis of cutaneous branch of peroneal artery is superior to lateral
      skin flap transfer by anastomosis of main trunk of peroneal artery with the merit
      of simple procedure, minimal trauma and more physiological circulation
      established.

PMID- 17017135
TI  - [Clinical application of sural neurocutaneous island flaps].
AB  - OBJECTIVE: To explore the clinical application characteristics of sural
      neurocutaneous island flaps. METHODS: Sural neurocutaneous island flaps were used
      to repair the skin defect accompanied bone and tendon exposure in the lower leg,
      around the ankle and foot in 21 cases, including 4 cases to repair the foreside
      of the foot back . Direct flap was used in 5 cases and reverse flap in 16 cases.
      Meanwhile the coverage and formation of sural nerve were surveyed together with
      the starting point of peroneal perforator. RESULTS: All the 21 sural flaps were
      survived, including sural nerve (18 cases) anastomose 12 cases, single trunk 4
      cases, double trunk 2 cases. The anastomose site of medial sural cutaneous nerve
      and the communicating branch of lateral sural cutaneous nerve was at the point of
      11 - 14 cm above the ankle in 12 cases. The lower was the anastomose site, the
      shorter was the sural nerve. The site is 4 - 7 cm above the ankle in 15 out of 18
      sural nerve perforator branch cases, and the other 3 cases is 10, 11, 11.5 cm
      above the ankle respectively. CONCLUSIONS: Sural neurocutaneous island flaps are
      easy to separate. Major arteries are not injured. It is the ideal flap to repair
      the skin defect accompanied by bone and tendon exposure in lower leg, around
      ankle and foot. The nerve must be anastomosed when repairing the heel.

PMID- 17017136
TI  - [Clinical analysis about survival condition of different types of platysma
      myocutaneous flaps].
AB  - OBJECTIVE: To compare the postoperative outcome among different types of platysma
      myocutaneous flaps by reviewing 54 cases. METHODS: From 1984 to 2004, 54 patients
      with oral cancer underwent immediate reconstruction of intraoral defects using
      the platysma myocutaneous flaps. In 54 cases, 12 cases were transversal platysma
      myocutaneous flaps and the other 42 cases were vertical platysma myocutaneous
      flaps. In these 42 cases, 26 cases preserved facial artery and vein yet 16 cases
      didn't preserve them. The survival condition of these flaps were compared.
      RESULTS: In the 12 cases of transversal platysma myocutaneous flaps, 10 cases
      survived totally and 2 cases had partial necrosis. In the 26 cases of vertical
      platysma myocutaneous flaps preserved facial artery and vein, 23 cases survived
      completely and 3 cases had partial necrosis. However, in the 16 cases of vertical
      platysma myocutaneous flaps in that facial artery and veins were not preserved,
      10 cases survived completely, whereas 4 cases had partial necrosis and 2 cases
      had complete necrosis. CONCLUSIONS: The survival rates of platysma myocutaneous
      flaps that didn't preserve facial artery and vein were low. Its clinical use
      should be prudent.

PMID- 17017137
TI  - [33 cases of craniofacial clefts: experience in diagnosis and treatment with
      tessier classification].
AB  - OBJECTIVE: To introduce our experience in diagnosis and treatment of 33 patients
      with Tessier craniofacial clefts. METHODS: 33 patients with craniofacial clefts
      were classified by Tessier classification. According to the type and severity of
      the clefts, various techniques, from simple local flap transfer to complicated
      osteotomy and bone grafting were used to correct the deformity in 29 patients.
      RESULTS: All patients who underwent corrective operation were satisfied with the
      result, and there were no complications. CONCLUSIONS: (1) Tessier classification
      is very important for plastic surgeon to find potential craniofacial deformities
      related to main signs. (2) No. 7 cleft is one of most common Tessier craniofacial
      clefts. (3) Each Tessier cleft is unique, therefore, the treatment plans cannot
      be standardized. Specific corrective operation must be performed on each patient
      according to the type and severity of the cleft, including simple local flap
      transfer to complicated osteotomy and bone grafting or distraction osteogenesis.

PMID- 17017138
TI  - [Experiment of using distraction osteogenesis to repair skull defect].
AB  - OBJECTIVE: To explore the possibility of using distraction osteogenesis to repair
      skull defect. METHODS: 17 goats with one year age were chosen randomly. The
      animals were divided to 3 groups. Group A includes 7 goats, a 3.0 cm x 2.2 cm
      rectangle skull defect is created on both sides of parietal area. Group B
      includes 5 goats, a 2.2 cm x 2.2 cm square skull defect was created on right side
      of parietal area. Group C includes 5 goats, a 3 cm x 1 cm rectangle skull defect
      was created on both sides of parietal area. Accordingly, different size of
      transport discs were created on right side of skull and the distraction apparatus
      is implanted. 3-D CT was done to measure the skull defect on group A.
      Biomechanical test was done on group B. Process of bone formation illustrated by
      histological stain, scan and transparent electric microscope was observed on
      group C. RESULTS: Group A measured by 3-D CT showed that skull defect of
      experimental side have been repaired by distraction osteogenesis. There was
      definitely difference between experimental and control side (P < 0.01). Group B
      measured by biomechanical test showed no definitely difference between
      experimental and normal side (maximum load P = 0.235 > 0.05, rigidity P = 0.213 >
      0.05). Group C showed that the process of bone formation was typical
      intramembranous. CONCLUSIONS: The evidence showed that skull defect of goat can
      be repaired by distraction osteogenesis.

PMID- 17017139
TI  - [The influences on mandibular development after removing the outer cortex of
      mandibular body in childhood minitype pigs].
AB  - OBJECTIVE: To study the influences on mandibular development after removing the
      outer cortex of mandibular body in childhood minitype pig. METHODS: Six childhood
      minitype pigs were selected as the experimental animals. The outer cortex of
      mandibular body measured as 3.0 cm x 1.5 cm was removed in one side, and the
      other side remained intact as the control. The changes of mandibular modality and
      occlusion relationship as well as the histological and biomechanical changes were
      studied 24 weeks after operation. RESULTS: There was no obvious difference
      compared with the control side in the height of the mandibular ramus and the
      length of the mandibular body, However, lateral deviation occlusion was found in
      some animals. The body thickness was thinner than that of the control side, there
      were no obvious biomechanical and histological differences between the two sides.
      CONCLUSIONS: There was less influence on the growth of mandibular bone after
      removing one side of the outer cortex of the mandibular body in childhood
      minitype pig. But further study should be done for the cause of the lateral
      deviation of the mandible in part of the animals.

PMID- 17017140
TI  - [Breast augmentation for correction of minor and moderate breast ptosis with
      anatomic breast implant].
AB  - OBJECTIVE: To evaluate a breast augmentation technique for correction of minor
      and moderate breast ptosis with an anatomic implant. METHODS: Fifteen patients of
      macromastia with minor and moderate breast ptosis were treated by using a breast
      augmentation with the anatomic implant under the breast gland. The results were
      judged with the the patient's satisfaction. RESULTS: All of the patient achieved
      big improvement of the breast ptosis with very satisfactory results. CONCLUSIONS:
      The minor and moderate breast ptosis could be achieved by using breast
      augmentation with an anatomic implant.

PMID- 17017141
TI  - [Analysis and treatment of the complications post polyacrylamide hydrogel
      injection for augmentation mammaplasty].
AB  - OBJECTIVE: To inquire into the reason why the postoperative complications of
      augmentation mammaplasty by injecting polyacrylamide hydrogel took place and to
      find the best method to deal with the complications. METHODS: 12 patients who
      accepted polyacrylamide hydrogel injection for augmentation mammaplasty were
      included in this study. Operations were performed to remove the polyacrylamide
      hydrogel. RESULTS: All patients didn't argue with the result, but the outside
      shape of mamma was not good post-operation. CONCLUSIONS: So-called standard
      injection method can't avoid the postoperative complications. The considerable
      therapy for the complications of polyacrylamide hydrogel was removing it by
      operation.

PMID- 17017142
TI  - [The evaluation of the treatment for the cavernous hemangioma and peripheral
      vascular disorders with copper needles].
AB  - OBJECTIVE: The goal of this study was to evaluate the effect of different methods
      of treating for the cavernous hemangioma and peripheral vascular disorders with
      copper needles. METHODS: 21 cases were treated with copper needle retention only,
      57 cases were treated with copper needle retention combined with a direct current
      of 6 - 9 V, both the inserted needles were kept in the site until the reaction
      was over, for about 10 to 20 days, 27 cases were treated with copper needle
      insertion combined with a direct current, and then the affection was ablated
      immediately. RESULTS: The early effective rate, the long-term effective rate, and
      the recurrence rate of the total cases were 94.3% , 88.6% and 28.6% respectively.
      Among the 3 groups, ablation of the affection after the use of copper needles and
      a direct current occupied the best results; copper needle retention combined with
      a direct current had a better result than copper needle retention only, and might
      shorten the time for therapy for about 42.6% (P < 0.01); their long-term
      effective rate were 100%, 89.5% and 71.4% respectively. CONCLUSIONS: The
      treatment for the cavernous hemangioma and peripheral vascular disorders with
      copper needles have a commendable result, copper needle retention combined with a
      direct current has a better result than copper needle retention only.

PMID- 17017143
TI  - [Clinical treatment of venous malformations with retained copper needles].
AB  - OBJECTIVE; To evaluate a technique with retained copper needles for the treatment
      of venous malformations. METHODS: With 78 venous malformation cases, there were
      three methods were applied for the treatment respectively, including copper
      needles in the lesion only, vascular ligation with the copper needles in the
      lesion, and electrical puncture with the copper needles in the lesion. RESULTS:
      There were totally 96% effective rate achieved in this clinical data.
      CONCLUSIONS: The retained copper needles technique may be a simple and effective
      method for the treatment of venous, malformations resulting in vessel
      denaturation, fibrosis and disappearance of structure.

PMID- 17017144
TI  - [Ear reconstruction using soft tissue expander in the treatment of congenital
      microtia].
AB  - OBJECTIVE: To explore surgical procedure of congenital microtia. METHODS: Ear
      reconstruction was made using soft tissue skin expander and autogenous rib
      cartilage framework. RESULTS: Long time follow-up showed that the flap of
      reconstructed ear was ruddy, soft, with normal sensory function; cartilage
      framework had no degeneration, absorption and deformation. In addition, the
      reconstructed ears were coincidence with the normal side on location, form and
      dimension. CONCLUSIONS: It was a good method for congenital microtia to use soft
      tissue skin expander together with autogenous rib cartilage framework at present
      time.

PMID- 17017145
TI  - [Treatment of primary lower limb lymphedema with ultrasonic assisted
      liposuction].
AB  - OBJECTIVE: To observe treatment effects of primary lower limb lymphedema using
      ultrasonic assisted liposuction. METHODS: Internal ultrasonic liposculpture
      system combined postoperative continual elastic stockings or bandages were used
      for reducing lymphatic burdens of the affected limbs by partly removal of
      lymphedematous tissues. RESULTS: Edema regression in the affected limbs were
      obvious at 2 weeks postoperative and kept to stable without recurrence during 1
      year follow-up. CONCLUSIONS: Ultrasonic assisted liposuction combined with
      elastic compression is safe and effective for the treatment of primary limb
      lymphedema.

PMID- 17017146
TI  - [Application of platysma flap in face lifting].
AB  - OBJECTIVE: To introduce a safe and simple method to improve the effect of face
      lifting. METHODS: During face lifting three anatomic dissection was applied. All
      the cases were performed with transferring the SMAS flap from the anterior ear to
      the posterior and fixing platysma flap with deep fascia of mastoid region, then
      removed fixed and sutured skin flap. RESULTS: 12 cases with satisfying effect
      were followed up for 6 - 12 months. No complications were found such as facial
      nerve injuring. CONCLUSION: The application of pedicle SMAS flap and platysma
      flap in face lifting is simple and safe.

PMID- 17017147
TI  - [Microscopic study on skin and soft tissue after repeated expansion].
AB  - OBJECTIVE: The study was to evaluate the microscopic changes on skin and soft
      tissue after repeated expansion for clinical work. METHODS: Six little pigs were
      divideded as: conventional expansion group, repeated expansion group, and blank
      control group. Histologic, ultrastructure and bFGF of the skin were observed and
      measured in each group after samples had been made. RESULTS: The skin and soft
      tissue after repeated expansion were healthy on the whole. Compared with the
      conventional expansion group, there was more microscopic change in the repeated
      expansion group. Collagen fibers were injured evidently. Cells were injured
      slightly and proliferated much more, and moreover, they were more activated. The
      content of bFGF was more higher. CONCLUSIONS: The skin and soft tissue after
      repeated expansion are healthy on the whole by more growth and more repair though
      repeated expansion may result in more injuries. So repeated expansion is safe and
      feasible.

PMID- 17017148
TI  - [Establishment of composite facial and scalp allograft transplantation model in
      canine].
AB  - OBJECTIVE: To develop an experimental model of composite facial and scalp
      allograft in canine in order to investigate technical and immunological aspects
      and functional recovery of facial muscles of this new approach to facial
      reconstruction. METHODS: (1) Anatomic study: Four mongrel dogs were used for
      anatomical dissection of the head and neck region and for harvesting flap
      experiment. (2) Autologous transplantation (group I): Three types composite
      facial and scalp autologous transplantation were performed in five mongrel dogs.
      Type I composite tissue flap (group I a n = 2) included bilateral external ear
      and orbicularis oculi muscle. Type II (group I b n = 1) included single-lateral
      external ear, orbicularis oculi muscle, external nose upper and lower lip. Type
      III (group I c n = 2) included single - lateral external ear and orbicularis
      oculi muscle. (3) Allograft transplantation (group II): In group II a (n = 2),
      two allograft transplantation were performed with type III composite facial and
      scalp . In group II b (n = 4), four allograft transplantation were performed with
      the modified type III composite facial and scalp which included single - lateral
      external ear, orbicularis oculi muscle and one third of inferior tarsal plate and
      palpebral conjunctiva. To prevent allograft rejection, Cyclosporin A (CsA) and
      Methylprednisolone (MP) or Prednisone (PS ) were combined used as
      immunosuppressive protocol . Dose of CsA was adjusted depending on its blood drug
      level. Electromyogram (EMG) of orbicularis oculi muscle was carried out at 4
      weeks, 6 weeks, 12 weeks and 6 months postoperation. RESULTS: (1) The facial
      anatomic characteristic of dog is similar to that of human being, external
      carotid artery and external jugular vein afford good blood supply to composite
      facial and scalp. (2) The dogs in group I c were long-term surviving with leakage
      of salivary juice. (3) In group II a (n = 2), one dog presented rejection
      reaction at 28th day postoperation, the reversal of rejection was achieved by
      increasing the dose of CsA and prednisone and with topical clobetasol for 2
      weeks, the dog survived indefinitely( > 309 days). In group II b (n = 4), there
      were three dogs survived indefinitely ( > 159 days, > 129 days, > 108 days)
      without complication, EMG showed the function of orbicularis oculi muscle was
      gradually improving. CONCLUSION: The modified type III composite facial and scalp
      allograft transplantation model is an ideal model for facial allograft
      transplantation study.

PMID- 17017149
TI  - [Effects of BMP-2 gene therapy on vascularization in repairing bone defects].
AB  - OBJECTIVE: To study the effects of BMP-2 gene therapy on vascularization in
      repairing bone defects. METHODS: The isolated rabbit mesenchymal stem cells
      (rBMSC), after being transfected by adenovirus carrying BMP-2 gene (Ad-BMP-2) and
      seeded on xenogeneic bone scaffolds, were used to repair 1.5 cm-long radius bone
      defects. Five methods were in use in the experiments: Ad-BMP-2 infected rBMSC
      plus antigen-free bovine cancellous bone (BCB, Group A), rBMSC-BCB plus
      reconstructed hBMP-2 (Group B1), Ad-LacZ infected rBMSC-BCB (Group C), rBMSC-BCB
      (Group D) and only BCB scaffolds (Group E). After 4, 8, and 12 weeks of the
      operations, capillary vessel ink infusion, vascular endothelial growth factor (
      VEGF) immunohistochemical staining and histological examination were conducted.
      RESULTS: After 4 weeks of the operations, usually in Group A one newly formed
      artery was found in every pore between the trabeculae of the BCB. The density of
      these intraosseous vessels was high in the periphery and decreasing towards the
      center of the grafts; by transmission electron microscopy, osteoblasts were
      always next to vascular endothelial cells and gradually developed into osteocytes
      with the increase of capillary vessel; VEGF expression were apparently enhanced
      in mesenchymocytes. CONCLUSIONS: BMP-2 gene therapy, by up-regulating VEGF
      expression, indirectly induces vascularization of grafts and is of great value to
      the treatment of bone in union and bone defects.

PMID- 17017150
TI  - [Effect of vacuum-assisted closure on the expression of urokinase-type
      plasminogen activator and urokinase-type plasminogen activator receptor in acute
      and chronic wounds healing].
AB  - OBJECTIVE: To study the effect of vacuum-assisted closure (V.A.C) on the
      expression of Urokinase-type plasminogen activator (uPA) and Urokinase-type
      plasminogen activator receptor(uPAR) protein in margin tissue of pigs with acute
      wounds and patients with chronic wounds. METHODS: Acute wounds were created on
      the two side of five male pigs' back, the experiment wounds on one side received
      V. A. C treatment and the control side received traditional treatment. Punch
      biopsies were taken from margin tissue of the wounds in 0, 1, 3, 6, 9, 12, 18, 25
      days after the V.A.C treatment. The uPA and uPAR positive cells were stained with
      immunohistochemical technique . Six human chronic wounds were also treated with
      the V. A. C treatment, and the samples of extravasate from those wounds were
      collected in 0, 1, 3, 5, 7 days after the treatment, and the levels of uPA and
      uPAR expression were examined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The expression of uPA and uPAR protein in margin tissues of pigs with
      acute wounds increased and peaked in 3 days after the treatment with V. A. C,
      then it presented rapidly downtrend, but the expression and staining in the
      experiment group were obviously higher than that of the control group. In the six
      chronic wounds, the high level expression of uPA and uPAR protein was decreased
      after the treatment with V. A. C. CONCLUSION: The V. A. C may increase the
      expression of uPA and uPAR protein in acute wound keratinocytes and decrease the
      high expression of uPA and uPAR in chronic wounds.

PMID- 17017151
TI  - [Experimental research of discordant tracheal xenotransplantation].
AB  - OBJECTIVE: To investigate the immunological rejection mechanism of tracheal
      xenotransplantation and xenografts as potential sources of trachea. METHODS: On
      SD rat model, a xenotransplanted tracheal from the guinea pig was established by
      wrapping it in the cervical muscles in situ. It was divided into cryopreserved
      group and uncryopreserved group. Under the examinations with histochemistry,
      immunofluorescence (IFL) and flow cytometry (FCM) techniques, the
      pathomorphological characteristics of the tracheal xenografts and the
      immunological rejection mechanism were evaluated. RESULTS: The tracheal
      allotransplantation with cryopreserved grafts wrapped by neck muscles was
      survived for a longer period. Histological examination revealed normal appearance
      of the allografts. The tracheal grafts patency was above 80%. However,
      cryopreserved tracheal xenografts of the guinea pig-to-rat maintained vitality
      for 14 days in maximum and 13.2 days on average, while the fresh tracheal
      xenografts only for 9 days in maximum, and 8 days on average. Acute rejection
      occurred in the tracheal xenotransplantation. A marked mononuclear-macrophage
      cellular infiltration mixed with eosinophils and lymphocyte was seen in the
      xenografts. Antibody (IgM, IgG) and complement (C3) deposition were also
      obviously detected by IFL in the xenografts. CD4 T+ cells and CD8+ T cells
      increased significantly in the vascular circulation. In all of the xenografts,
      complete loss of tracheal epithelium was associated with cartilage necrosis. The
      grafts patency was below 50%. This performance deteriorated with extended time
      periods. The fresh xenografts performed significantly worse than the
      cryopreserved xenografts. CONCLUSIONS: Acute rejection, caused by humoral immune
      reaction mainly integrated with cellular immunity, is the most notable
      characteristics in the guinea pig-to-rat tracheal xenotransplantation in situ.
      Cryopreservation can potentially reduce the antigenicity. The low antigenicity
      may inhibit the immunologic reaction relatively, so that prolonged survival of
      discordant cryopreserved tracheal xenografts could be achieved.

PMID- 17017152
TI  - [Analysis of ginsenosides in Sheng-Mai-Yin decoction by high performance liquid
      chromatography-diode array detection-electrospray mass spectrometry].
AB  - A method of high performance liquid chromatography coupled with diode array
      detection and electrospray ionization mass spectrometry (HPLC-DAD/MS) in negative
      ion mode was developed for the analysis of ginsenosides in Sheng-Mai-Yin
      decoction (Panax gingeng C. A. Mey, Ophiopogon japonicus (Thunb.) Ker-Gawl,
      Shisandra chinensis (Turcz.) Baill.). The analyses were preformed on a reversed
      phase C18 column (4.6 mm i.d. x 150 mm, 5 microm) using a binary eluent (10
      mmol/L ammonium acetate (A) and acetonitrile (B), 1 mL/min) under gradient
      conditions (60% A - 40% A at 0 - 30 min, 40% A - 30% A at 30 - 40 min). Seventeen
      ginsenosides (20 (R) -Rh1, Rh2, Rg3, Rg2; 20 (S) -Rh1, Rh2, Rg3, Rg2; Rf, Rg6,
      Rg5, F4, Rk1, Rk3, Rh4; 20 (S)- and 20 (R) -protopanaxatriol) were well separated
      and detected at 203 nm by a DAD detector. The effluent from the DAD detector was
      introduced into the electrospray ionization (ESI) source in a post-column
      splitting flow rate at 0.3 mL/min. In the mass spectrum two major ions [M - H]-
      and [M + AcO]- were observed for ginsenoside standards (20 (R) -Rh1, Rg3, Rh2; 20
      (S) -Rh1, Rg3, Rh2; 20 (S)- and 20 (R) -protopanaxatriol) and ginsenosides in
      Sheng-Mai-Yin decoction. Some other ions [M - Glc - H]-, [M - 2Glc - H]-, [M -
      Rha - H- and [M - Rha - Glc - H]- were also found in the mass spectrum of
      ginsenosides of Sheng-Mai-Yin decoction. In the decoction process ginsenosides
      changed into constituents of moderate and low polarity by hydrolysis,
      isomerization and dehydration at the site of C-20 and hydrolysis reaction also
      occurred at the site of C-3 or C-6. The work above presents a quick and accurate
      assay method which can could be used for the qualitative analysis of ginsenosides
      in Sheng-Mai-Yin decoction and the quality control of Sheng-Mai-Yin preparation.

PMID- 17017153
TI  - [Determination of three nitroimidazole residues in royal jelly by high
      performance liquid chromatography-tandem mass spectrometry].
AB  - A method for analysis of trace metronidazole (MTZ), dimetridazole (DMZ) and
      ronidazole (RNZ) residues in royal jelly was developed by high performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS). After samples were
      dissolved in sodium hydroxide solution to disassociate target analytes from
      matrix, liquid-liquid extraction methods by ethyl acetate solvent were used.
      Matrix effects were minimized and good quantitation results were obtained by
      using highly-selective reaction monitoring (H-SRM) technology when deuterated
      dimetridazole (dimetridazole-D3) was selected as internal standard. Limits of
      detection (LODs) were 1.0 microg/kg for DMZ, 0.5 microg/kg for MTZ and RNZ (S/N >
      5). Limits of quantitation (LOQs) were 2.0 microg/kg for DMZ, 1.0 microg/kg for
      MTZ and RNZ (S/N > 10). The linear ranges were 2.0 - 200 microg/L for all target
      analytes. Recoveries and relative standard deviations (RSDs) were in the ranges
      of 96.6% - 110.6% and 2.1% -7.4%, respectively. This method is suitable for
      statutory residue testing in the National Residue Surveillance Plan in China and
      meets the requirement for export.

PMID- 17017154
TI  - [Determination of trace microcystins in water by ultra performance liquid
      chromatography/tandem mass spectrometry].
AB  - An analytical method for the analysis of trace microcystins (MCYST) in water was
      developed using solid phase extraction (SPE) for enrichment and ultra performance
      liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) for detection. One
      litre of water was passed through SPE columns, the extracted sample was rinsed
      off by 10 mL methanol, then evaporated to 1.0 mL before being analyzed with
      UPLC/MS/MS. The effect of formic acid concentration in the mobile phase on the
      sensitivity was studied and the results showed that 0.1% was the optimum
      concentration. Four microcystins, MCYST-LR, RR, LW, LF, can be separated and
      detected in 5 min, which is much shorter than that by the conventional liquid
      chromatography. The detection limits were 1.3 - 6.0 ng/L, and the recoveries were
      91.1% - 111%. The calibration curves showed good linearity in the range of 1.0
      microg/L - 1.0 mg/L with correlation coefficients larger than 0.99. The method
      was also applied to determine MCYST in real water samples from three reservoirs
      in Zhejiang Province, and the results showed that the concentrations of LR and RR
      were 0.044 7 - 2.73 microg/L and 0.020 8 - 1.36 microg/L respectively, and LW and
      LF were not detected.

PMID- 17017155
TI  - [Study on the pyrolysis behavior of geranyl-beta-D-glucopyranoside by gas
      chromatography-mass spectrometry].
AB  - In order to investigate the pyrolysis behavior of the flavor precursor of geranyl
      beta-D-glucopyranoside, the glycoside was pyrolyzed at 200, 300, 400 degrees C in
      an on-line pyrolyzer under anaerobic conditions and in an off-line mode
      separately. Gas chromatography-mass spectrometry (GC/MS) was used for the
      qualitative and quantitative analysis of the pyrolysis products. the results.
      Little geranyl-beta-D-glucopyranoside was pyrolyzed at 200 degrees C and there
      were a large amount of geraniol and little by-products produced at 300 degrees C.
      With the increasing temperature to 400 degrees C, both the pyrolytic products and
      by-products were significantly increased. Therefore, it indicated that the
      optimized temperature of pyrolysis was 300 degrees C. The main pyrolysis product
      of the glycoside was geraniol. It showed the primary decomposition reaction took
      place with the breaking of glycosidic linkage, the cleavage of O-glycosidic bond
      as expected. The on-line mode experiment was a rapid and good qualitative method
      for the pyrolysis, and the off-line mode can be used as a quantitative method
      based on the qualitative analysis.

PMID- 17017156
TI  - [Analysis of volatile constituents from leaves of plants by gas
      chromatography/mass spectrometry with solid-phase microextraction].
AB  - A method for analyzing volatile constituents from plant leaves with gas
      chromatography/mass spectrometry (GC/MS) coupled with solid-phase microextraction
      (SPME) was developed. The volatile compounds from the plant leaves inside a
      sealed flask maintained at 45 degrees C in a water bath were efficiently
      extracted with Polyacrylate (85 microm) SPME fibers prior to perform GC/MS
      analysis. The GC/MS analysis indicated that the volatile compounds from the plant
      leaves which is easy to be damaged by Tetraychus vienneis include relative large
      amounts of cis-3-hexenyl ester acetic acid, cis-3-hexenyl ester butanoic acid and
      alpha-famesene. These compounds were preliminarily confirmed to be accountable
      for attracting Tetraychus vienneis. This finding may lead to identify biological
      species for preventing and treating Tetraychus vienneis.

PMID- 17017157
TI  - [Determination of polychlorinated dibenzo-p-dioxins and dibenzo-furans in
      sediment by accelerated solvent extraction, fluid management systems and high
      resolution gas chromatography/high resolution mass spectrometry].
AB  - A rapid, sensitive and accurate method has been developed for the determination
      of seventeen 2, 3, 7, 8-substituted congeners of polychlorinated dibenzo-p
      dioxins and dibenzo-furans (PCDD/Fs) in sediment using isotope dilution high
      resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS).
      Dibenzo-p-dioxins and dibenzo-furans were extracted from samples by accelerated
      solvent extraction (ASE) and then purified by fluid management systems (FMS) with
      silica column, alumina column and carbon column. Confirmation and quantitative
      analysis at pg/g level of PCDD/Fs were performed by HRGC/HRMS using voltage
      selective ion record (VSIR) mode. Recoveries of fifteen isotopically labeled
      compound solutions (LCS) and the precision and recovery standards (PAR) were
      found to be in the range of 49.8% -85.3% and 93.2% - 113.8%, respectively. The
      detection limits of the method for both 2, 3, 7, 8-tetrachloro-dibenzo-furan
      (TCDF) and 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin (TCDD) were determined to be
      0.1 pg/g. This method not only meets the requirements of international standards,
      but also shortens analysis time from 2 weeks to 2 days.

PMID- 17017158
TI  - [Study of organosulfur compounds in fresh garlic by gas chromatography/mass
      spectrometry incorporated with temperature-programmable cold on-column
      injection].
AB  - For the analysis of organosulfur compounds in fresh garlic, a gas
      chromatographic/mass spectrometric (GC/MS) method is proposed using temperature
      programmable cold on-column injection and cold solvent extraction of the fresh
      garlic. This was carried out under the conditions of cryogenic process from
      extraction to column separation. Hence, a valid identification can be achieved
      about the primary components in garlic extract before thermo-degradation. The
      obtained results showed that 3-vinyl-4H-1, 2-dithiin and 2-vinyl-4H-1, 3-dithiin
      were the major compounds in the garlic extract with minor amounts of S-methyl
      methanethiosulfinate, diallyl disulfide, trisulfide-di-2-propenyl. A comparative
      study of chemical compounds was performed between garlic extract by cold solvent
      and garlic oil by stream distillation. The degradation and formation of major
      organosulfur compounds in the garlic extract were also explored.

PMID- 17017159
TI  - [Optimization of high performance liquid chromatographic method for analysis of
      kudzu root crude extract].
AB  - Kudzu root is an important traditional Chinese herb. Its crude extract has been
      used in the treatment of hypertension and angina pectoris in China. Several
      parameters for high performance liquid chromatography (HPLC) analytical method
      for kudzu root extract, including HPLC model, mobile phase, additive and gradient
      conditions have been optimized. The HPLC retention parameters a and c, and the
      peak shape parameters sigma and tau of 25 chromatographic peaks were obtained
      accurately and rapidly using five linear gradients and were calculated using
      CSASS software. The CSASS software was then used to simulate the gradient
      conditions in the experiments, and the optimized condition was obtained. The
      comparison of the simulated and real chromatogram profiles showed that the
      potential of simulation using the CSSASS software as compared to that of the real
      experimental conditions was precise. Reversed-phase HPLC model and the mobile
      phase of (A) acetonitrile containing 0.1% (v/v) acetic acid and (B) water
      containing 0.1% (v/v) acetic acid were used. The optimized gradient profile
      showed a linear increase as follows: from 5% A to 35% A at 0 - 33 min; from 35% A
      to 100% A at 33 - 50 min, and then the HPLC system was held for 5 min. The
      reproducibility and precision of the method were investigated. The relative
      standard deviations (RSDs) of retention time, peak height, and peak area were
      less than 0.25%, 11%, and 4.9%, respectively, which showed that the method was
      stable, reliable, and reproducible.

PMID- 17017160
TI  - [Simultaneous determination of 17 underivatized amino acids in donkey-hide glue
      by reversed-phase high performance liquid chromatography-evaporative light
      scattering detection].
AB  - An analytical method to determine 17 underivatized amino acids in donkey-hide
      glue was established with reversed-phase high performance liquid chromatography
      (HPLC) coupled with evaporative light-scattering detection (ELSD). A Prevail C18
      column was used with the mobile phase of acetonitrile-0.7% trifluoroacetic acid
      containing 5.0 mmol/L heptafluorobutyric acid. Under the condition of solvent
      gradient elution, the temperature of drift tube was 115 degrees C and the gas
      flow rate was 2.5 L/min. The 17 amino acids were separated within 25 min. The
      good linearities between the logarithm of peak area and logarithm of mass
      concentration of amino acids were obtained in a range of mass concentrations from
      0.073 g/L to 2.327 g/L. The recoveries of 17 amino acids were 93.5% - 104.8% with
      the relative standard deviations (RSDs) of 0.58% - 2.88%. The lowest detection
      limits of amino acids were from 18.2 mg/L to 54.6 mg/L with 3 times the signal to
      noise ratio. This HPLC-ELSD method is rapid, simple and accurate. It can be used
      for the direct determination of 17 underivatized amino acids in donkey-hide glue.
      It also serves as a good reference for the determination of amino acids in other
      fields, such as pharmaceutical analysis.

PMID- 17017161
TI  - [Preparation of soybean isoflavone glucosides by reversed-phase high performance
      liquid chromatography].
AB  - A method was established for the isolation of soybean isoflavone glucosides from
      the total isoflavone extracts of soybean using preparative reversed-phase high
      performance liquid chromatography (RP-HPLC). The total isoflavone extracts were
      separated into four parts by solvent extraction, those are the ethyl acetate
      extract, butanol extract, precipitate (D4), and the remaining aqueous phase. The
      part D4 containing soybean isoflavone glucosides was acquired and subjected to
      preparative HPLC for the isolation of target components. A preparative Nova-Pak
      HR C18 column (100 mm x 25 mm i. d. , 6 microm) was used in the preparation
      process. By isocratic elution with methanol-0.1% aqueous acetic acid (23:77, v/v)
      as the mobile phase at a flow rate of 20 mL/min, followed by concentration and
      desalination, three soybean isoflavone glucosides were obtained and subsequently
      identified by mass spectrometry as daidzin, glycitin, and genistin. HPLC analysis
      showed that the purities of the three soybean isoflavone glucosides were all
      higher than 99%.

PMID- 17017162
TI  - [Study on quality control and fingerprint of Chinese traditional medicine
      Yinhuang oral liquid].
AB  - The chromatographic fingerprint of Chinese traditional medicine, Yinhuang Oral
      Liquid together with its original materials Radix Scutellariae and Flos lonicera
      was established by high performance liquid chromatography (HPLC). At the same
      time, baicalin and chlorogenic acid in the Yinhuang Oral Liquid were also
      quantitatively determined. The analysis was performed on a Lichrospher C18 column
      (250 mm x 4.6 mm i. d. , 5 microm) and with gradient elution. The optimum
      conditions were explored. The mobile phase A was methanol and the mobile phase B
      was 0.1% H3PO4 aqueous solution. The wavelength of 254 nm was selected for
      detection. Finally, the data of fingerprints of 6 samples of Yinhuang Oral Liquid
      were processed with two different mathematic methods. This proposed method
      demonstrated good stability for the 6 samples of Yinhuang Oral Liquid. In the
      comparison of the common peaks in chromatogram of Yinhuang Oral Liquid with those
      of crude herbs, most of them could be matched well.

PMID- 17017163
TI  - [Determination of egg-yolk phosphatidylcholine by normal-phase high performance
      liquid chromatography with evaporative light scattering detection].
AB  - A method for the determination of egg-yolk phosphatidylcholine by normal-phase
      high performance liquid chromatography (NP-HPLC) with evaporative light
      scattering detection (ELSD) was developed. Yolk phosphatidylcholine was
      successfully separated on a Nova-Pak Silica 60A column (3.9 mm i.d. x 150 mm, 4
      microm), using hexane-isopropanol-water containing 3% acetic acid (35: 65: 8,
      v/v/v) as mobile phase at a flow rate of 1.0 mL/min. The drift tube temperature
      and air carrier gas pressure of the ELSD were set at 50 degrees C and 350 kPa,
      respectively. The linear detection range was 0.16 - 1.61 g/L (r2 = 0.997 9) and
      the limit of detection (LOD) was 0.64 microg with excellent relative standard
      deviation (RSD) of 3.2% (n = 5). The recovery was in the range of 98.2% - 128.2%.
      The results indicated that this method is accurate, rapid, simple and
      reproducible, and thus suitable for the analysis of egg-yolk phosphatidylcholine
      in real samples.

PMID- 17017164
TI  - [Comparison in hydrophobic selectivity for two types of reversed-phase high
      performance liquid chromatography packing material].
AB  - Two types of novel reversed-phase packing materials were made by adding TiO2/
      SiO2 (or ZrO2/SiO2) and octadecyltrichlorosilane into toluene with stirring and
      refluxing for 36 h. TiO2/SiO2 and ZrO2/SiO2 particles were prepared by a layer-by
      layer self-assemble technique and consist of micrometer-sized silica spheres as
      cores and nanometer-sized zirconia or titania as surface coating. The carbon
      loading of C18-bonded TiO2/SiO2 was 11.51% and that of C18-bonded ZrO2/SiO2 was
      9.62%. The hydrophobic selectivity and sensitivity were studied respectively and
      compared in details; the results showed that the packing supports both acted as
      true reversed chromatographic stationary phase with similar hydrophobic
      selectivity. The chromatographic behaviors of the two types of novel reversed
      phase packing material were evaluated with nine aromatic compounds. The
      chromatographic studies showed that either of the packing materials would be a
      good choice to separate aromatic compounds, however, the selectivity of C18
      bonded TiO2/SiO2 was a little better than that of C18-bonded ZrO2/SiO2.

PMID- 17017165
TI  - [Determination of aromatics in light petroleum products by comprehensive two
      dimensional gas chromatography].
AB  - In recent years, comprehensive two-dimensional gas chromatography (GC x GC) have
      been used widely, and the applications of this technique to many fields have
      already been reported. In the standard method of oil analysis, the concentrations
      of aromatics and naphthalene hydrocarbons in light petroleum products must be
      detected by more than two methods. Mono-aromatics, di-aromatics etc. in light
      petroleum products were detected only by comprehensive two-dimensional gas
      chromatography. After the proper selection of column system and optimization of
      chromatographic conditions, the method can achieve the group separations of
      paraffins, olefins, naphthenes, aromatics with 1 to 2 rings and some target
      components in light petroleum products with good reproducibility and good
      precision. The recoveries of standard compounds were 89.5% - 106.1%, and the
      relative standard deviations of repeatedly detecting the components were all
      lower than 5.8%. It took only 30 min to finish a determination.

PMID- 17017166
TI  - [Determination of vapor pressures of six polybrominated biphenyl congeners by gas
      chromatography].
AB  - Polybrominated biphenyls (PBBs) are a class of new type organic pollutants. They
      have been widely used as flame retardants to reduce the fire risk on plastics,
      carpets, electronic equipment, textiles and building materials around the world.
      With a gas chromatographic retention time technique, vapor pressures (p) of six
      polybrominated biphenyls (PBB15, PBB26, PBB31, PBB49, PBB103 and PBB153) were
      determined as a function of temperature with dichlorodiphenyl trichloroethane
      (DDT) acting as a reference substance. Vapor pressures at 298.15 K ranged from
      0.01 Pa for dibrominated biphenyl to 10(-6) Pa for hexabrominated biphenyl.
      According to these vapor pressures at different temperatures, Antoine parameters
      (A, B, C) of six PBBs were regressed with the least square method. The
      correlations between vapor pressure and temperature for six PBBs were obtained.
      In addition, the correlations between vapor pressures and molecular connectivity
      indexes have been studied with correlation coefficients greater than 0.99 and
      standard errors less than 0.08. The vapor pressures of PBBs were also estimated
      by their molecular connectivity indexes.

PMID- 17017167
TI  - [Simultaneous determination of levodopa and methyldopa in human serum by
      capillary electrophoresis].
AB  - A simple capillary electrophoresis method was developed for the determination of
      levodopa and methyldopa in human serum. The effects of pH and concentration of
      buffer, voltage and injection time on separation were investigated. As a result,
      an optimized separation was obtained with a fused-silica capillary of 60.2 cm (50
      cm effective length) x 75 microm i. d. in a running buffer of 40 mmol/L sodium
      tetraborate (pH 9.5) with an applied voltage of 22 kV at 25 degrees C. Sample
      introduction was performed at 3.45 kPa (0.5 psi) for 7 s and on-column detection
      was made with a diode array detector at 200 nm. The linear responses covered the
      ranges from 1.0 to 64.0 mg/L (r = 0.999 8) for methyldopa and from 1.0 to 71.0
      mg/L (r = 0.999 4) for levodopa. The detection limits (S/N = 3) of methyldopa and
      levodopa were shown to be 0.6 mg/L and 0.8 mg/L, respectively. The recoveries for
      levodopa and methyldopa in human serum were between 82.8% and 88.8% with relative
      standard deviations between 2.10% and 2.63%.

PMID- 17017168
TI  - [Determination of alkaloids in cigarettes by capillary zone electrophoresis].
AB  - The separation of cigarette alkaloids was reported and performed with tartaric
      acid buffer solution by capillary zone electrophoresis (CZE). A buffer solution
      of pH 2.8, 410 mmol/L tartaric acid was used as the running buffer for the
      determination of cigarette alkaloids in CZE. The detection sensitivity and
      resolution with the tartaric acid buffer solution were better than those with
      phosphate buffer. The sample extraction conditions, buffer electrolyte, pH and
      concentrations were investigated for the alkaloids separation and determination.
      The linear range, detection limits, reproducibilities and recoveries of the
      cigarette alkaloids were 0.06 - 0.80 mg/L for nicotine (0.006 - 0.10 mg/L for
      other alkaloids), 0.002 - 0.01 mg/L, 2.2% - 10% and 87.6% - 102%, respectively.

PMID- 17017169
TI  - [Study on factors affecting reproducibility of migration time in capillary
      electrophoresis].
AB  - The effects of running buffer on reproducibility of the migration time in the
      modes of capillary zone electrophoresis (CZE) and micellar electrokinetic
      capillary chromatography (MECC) were investigated. The parameters include
      concentration, pH value and the properties change of the running buffer. The
      results showed that the reproducibility of migration times may be improved
      through three approaches. First, the correlation between running buffer
      concentration and migration time was established and the running buffer
      concentration was determined by conductivities in order to improve the
      reproducibility. Second, it was found that the residual running buffer in the
      capillary showed significant influence on the repeatability of migration times.
      Thus, appropriate running or washing procedure between separations is necessary.
      Finally, the inlet reservior buffer plays an extremely important role in
      affecting the migration behaviors of solutes. Through improving the test
      apparatus, reproducible migration time was achieved as a result of increasing the
      frequency of replacing the buffer in the inlet reservior.

PMID- 17017170
TI  - [Preparation of norvancomycin-bonded chiral silica monolithic column for
      capillary electrochromatography and its applications].
AB  - Silica-based monolithic column with high rigidity and good permeability was
      prepared by a modified sol-gel technology, characterized by shorter fabrication
      process and higher success rate. A macrocyclic antibiotics-based chiral
      monolithic column was successfully prepared by modifying the monolithic matrix
      with a homemade macrocyclic antibiotics--norvancomycin by adopting a single-step
      on-column derivatization process. The newly synthesized column was assessed for
      its enantioselectivity in chromatographic modes of reversed-phase and polar
      organic-phase. The effect of the mobile phase composition on the retention and
      enantioselectivity of the system was also investigated in detail. It was shown
      that beta-receptor blockers can be best resolved under the mobile phase
      composition of methanol-acetonitrile-triethyl-amine-acetic acid (80: 20: 0.1 :
      0.1, v/v). Under reversed-phase conditions, a nearly linear increase of
      electroosmotic flow (EOF) was observed with the pH changing from 4.0 to 7.0,
      which shows that the predominant source of EOF is still resulting from the silica
      backbone while the chiral selector of norvancomycin contributes little. A number
      of racemic pharmaceuticals with different structures were separated in reversed
      phase mode with different resolutions. It was shown experimentally that the
      column prepared in this way had broader enantioselectivity as well as better
      batch-to-batch reproducibility.

PMID- 17017171
TI  - [Study on homogeneity of enzymatic degradation of chitosan as biomaterials by gel
      permeation chromatography].
AB  - Chitosan is an important biomedical material, and its degree of deacetylation is
      a main parameter of its biodegradation. Gel permeation chromatography was used to
      investigate the lysozymic degradation of two types of chitosan samples (A and B)
      with similar degree of deacetylation and relative molecular mass but with
      different distributions of two units of N-acetyl-D-glucosamine and D-glucosamine.
      Weight average relative molecular mass, polydispersity and gel permeation
      chromatograms during the degradation process were obtained. It was found that
      chitosan sample A with random distribution of the two units underwent a
      homogeneous degradation process while chitosan sample B with block distribution
      underwent a heterogeneous degradation process. The results suggest that the
      homogeneity of the degradation of chitosan materials by lysozyme depends on the
      distribution type of the two units, which can help to design chitosan-based
      biomedical devices.

PMID- 17017172
TI  - [Determination of monosaccharides in Sargassum hemiphyllum (Turner) C. Ag.
      polysaccharides by ion chromatography].
AB  - Sargassum hemiphyllum polysaccharides (SHP) was extracted from dry Sargassum
      hemiphyllum (Turner) C. Ag. powder using 60 - 80 degrees C purified water and
      then hydrolyzed with 4.0 g/L trifluoroacetic acid at 80 degrees C. Without any
      derivatization reaction, the determination of monosaccharides in SHP was
      developed by anion-exchange chromatography with pulsed amperometric detection
      with an Au working electrode and an Ag/AgCl reference electrode. Monosaccharides
      were separated on a CarboPac PA10 anion-column (2 mm i. d. x 250 mm) by using
      isocratic elution consisting of 14 mmol/L sodium hydroxide at a flow rate of 0.20
      mL/min. Six monosaccharides, xylose, galactose, arabinose, glucose, rhamnose and
      fructose, contained in SHP were separated and determined. Their contents in SHP
      were 2 200, 820, 98, 4 560, 358 and 740 mg/kg, respectively. The recoveries of
      the six monosaccharides were in the range 86.0% - 108.0%. The detection limits
      for these monosaccharides ranged from 5.6 to 89.6 microg/kg. The experimental
      results showed that SHP mainly consisted of xylose and glucose with smaller
      quantities of galactose, arabinose, rhamnose and fructose. This method is
      suitable for the determination of monosaccharides without any derivatization
      reaction at the level of microg/kg in dry algae with high sensitivity and good
      precision.

PMID- 17017173
TI  - [Simultaneous determination of L-phenylalamine and beta-phenylethanol in
      fermentation broth by high performance liquid chromatography].

PMID- 17017174
TI  - [Determination of benzo[a]pyrene in vegetable oils by HPLC coupled with matrix
      solid phase dispersion].

PMID- 17017175
TI  - [Direct separation of beta-thymidine and alpha-thymidine by high performance
      liquid chromatography using chiral column].

PMID- 17017176
TI  - [Determination of ephedrine and pseudoephedrine in maxingshigan tang by ion pair
      HPLC].

PMID- 17017177
TI  - [Rapid determination of micro-amount of formic acid in glacial acetic acid by gas
      chromatography without derivatization].

PMID- 17017178
TI  - [Determination of trace methanol, methyl tert-butyl ether and other compounds in
      light hydrocarbons by gas chromatography].

PMID- 17017179
TI  - [Development of a liner tube for at-column injection on wide bore capillaries].

PMID- 17017180
TI  - [Separation of xanthones by reversed-phase capillary electrochromatography].

PMID- 17017181
TI  - [Determination of nitrogen, sulfur and chlorine in fish samples by burning in
      oxygen flask and ion chromatography].

PMID- 17017182
TI  - [The expression of transforming growth factor beta1, interleukin-6, 11 and 17 in
      nasal mucosa of allergic rhinitis patients].
AB  - OBJECTIVE: To explore the protein expression of transforming growth factor (TGF)
      beta1, interleukin (IL)-6, 11, and 17 in the nasal mucosa of allergic rhinitis
      patients. METHOD: The protein expression of TGF-beta1, IL-6, 11, and 17 in the
      inferior turbinate tissues from 19 allergic rhinitis patients and from 21 non
      allergic patients underwent nasal septum operation was detected by enzyme-linked
      immunosorbent assay. RESULT: (1) Compared with tissues from non-allergic
      patients, the expression of TGF-beta1 protein was significant increased in the
      tissues from allergic rhinitis patients (P < 0.01); (2) As to the protein
      expression of IL-6, 11 and 17, there was no significant difference between
      allergic rhinitis patients and non-allergic patients (P > 0.05); (3) The
      expression of TGF-beta1, IL-6, 11, and 17 was similar between the allergic
      rhinitis patients with and without asthma (P > 0.05). CONCLUSION: TGF-beta1 ,
      while not IL-6, 11 and 17, may play a role in the tissue remodeling processes in
      allergic rhinitis. This expression profile may contribute to the difference in
      the tissue remodeling between allergic rhinitis and asthma.

PMID- 17017183
TI  - [Clinical analysis of isolated sphenoid disease first manifesting headache and/or
      ophthalmic symptoms].
AB  - OBJECTIVE: To improve the diagnosis and treatment of isolated sphenoid disease
      first manifesting headache and/or eye symptoms. METHOD: The clinical data of 25
      cases suffering from isolated sphenoid disease first manifesting headache and/or
      eye symptoms from 1996 to 2005 were analyzed retrospectively, and the correlated
      documents were reviewed. RESULT: In this group of the 25 patients, 21 failed to
      be diagnosed at the first time of medical consultation. The diagnosis confirmed
      by CT or MRI and pathology included 7 cases with isolated sphenoiditis, 4 with
      mycosis, 3 with sphenoid cysts, 6 with purulent sphenoid cysts, 2 with polyps and
      sphenoiditis, 1 with foreign body, 1 with craniopharyngioma, and 1 with
      oncocytoma. All of the patients underwent endoscopic sphenoid surgery. The
      symptoms of 24 cases of the patients were improved or disappeared after the
      operations. CONCLUSION: This isolated sphenoid diseases were easily misdiagnosed.
      The diagnosis depends on CT or MRI and nasal endoscopy. CT by three-dimensional
      reconstruction can provide more special and precise information. Endoscopic sinus
      surgery is effective and safe technique for the treatment of the disease.

PMID- 17017185
TI  - [Expression of neuropilin-1 in human laryngeal carcinoma and cell lines].
AB  - OBJECTIVE: To study the expression of Neuropilin-1 in human carcinoma and
      papilloma of larynx specimens and carcinoma cell lines Hep-2. METHOD: The
      expression of Neuropilin-1 in human laryngeal carcinoma, papilloma specimens were
      investigated by immunohistochemical staining; the expression of Neuropilin-1 mRNA
      in human laryngeal squamous cell carcinoma, papilloma specimens and cell lines
      were examined by using RT-PCR. RESULT: Immunohistochemical analysis revealed that
      NRP-1 was expressed in all human laryngeal squamous cell carcinoma specimens but
      was absent in nonmalignant laryngeal tissue. The mRNA of NRP land Hep-2 cell
      lines are positive in 24 of 28 human laryngeal carcinoma specimens but not
      negative in nonmalignant laryngeal specimens. CONCLUSION: Neuropilin-1 was
      expressed in most of human laryngeal carcinoma specimens and cell lines but not
      expressed in nonmalignant tissue. It suggests that the expression of Neuropilin-1
      may be related to the risk and development of laryngeal carcinoma and has high
      distinguishability.

PMID- 17017184
TI  - [The features of four types of operation for treating chronic hypertrophy
      rhinitis and ultrastructure observation of the inferior turbinate mucosa].
AB  - OBJECTIVE: To assess the features of four types of operation for treating chronic
      hypertrophy rhinitis and to observe the ultrastructure of inferior turbinate
      mucosa. METHOD: Eighty-eight cases of chronic hypertrophic rhinitis (HR) were
      treated by transnasal endoscopic submucous inferior turbinate resection (group
      A), thirty cases of HR were treated by partial inferior turbinectomy (group B),
      thirty six cases of HR were treated by bipolar radiofrequency ablation on
      inferior turbinate (group C), ten cases of HR were treated by injection of
      sclerosing agent (group D). The efficacy in the three groups (A,B,C) and the
      features of four types operation were compared and the ultrastructure of inferior
      turbinate was observed both preoperatively and postoperatively. RESULT: Four
      groups of HR were followed up 4 months to half year after operation, effective
      rate was 97.4 (group A) 100% (group B) and 93.4% (group C) respectively, while
      group A, group B and group C effective rate had no significant difference among
      them. Group A and group C have more advantages compared to the other 2 groups for
      they remained good ultrastructure of inferior turbinate mucosal cilia after 4 to
      6 months postoperatively. CONCLUSIONS: The use of transnasal endoscopic submucous
      inferior turbinate resection and bipolar radiofrequency ablation for treatment of
      chronic hypertrophy rhinitis are effective modality for the treatment of chronic
      hypertrophy rhinitis.

PMID- 17017186
TI  - [Multivariate survival analysis in patient with laryngeal squamous cell
      carcinomas].
AB  - OBJECTIVE: This study was designed to analyze the most important factors
      affecting the prognosis of the patients with laryngeal squamous cell carcinoma
      (LSCC). METHOD: The expression of S-phase kinase associated protein 2(Skp2), p27,
      E-cadherin (E-cad) and alpha-catenin (alpha-cat) in 79 cases of LSCC and 10 cases
      of adjacent normal laryngeal mucosa tissues were evaluated by SP
      immunohistochemistry methods, 12 clinicopathological factors affecting the
      prognosis of LSCC were analyzed using univariate model and multivariate
      regression model. RESULT: (1) The overexpression rate of Skp2 was significantly
      higher in LSCC (53.16%) than in adjacent normal laryngeal mucosa tissue (0%) (P <
      0.05). The overexpression rate of p27 was significantly lower in LSCC (30.38%)
      than in adjacent normal laryngeal mucosa tissue (90%) (P < 0.05). The positive
      expression rate of E-cad was significantly lower in LSCC (34.18%) than in
      adjacent normal laryngeal mucosa tissue (100%) (P < 0.05). The positive
      expression rate of alpha-cat was significantly lower in LSCC (40.51%) than in
      adjacent normal laryngeal mucosa tissue (100%) (P < 0.05). (2) There was a
      significantly higher 5-year survival rate in reduced Skp2 expression group
      (72.18%) when compared with that of Skp2 overexpression group (44.17%) in LSCC (P
      < 0.01). There was a significantly higher 5-year survival rate in p27
      overexpression group (72.98%) when compared with that of reduced p27 expression
      group in LSCC (51.13%) (P < 0.01). The 5-year survival rates of positive E-cad
      expression group and positive alpha-cat expression group in LSCC were 63.80% and
      81.74% respectively, the 5-year survival rates of negative E-cad expression group
      and negative alpha-cat expression group were 50.68% and 41.09% respectively.
      There were significantly higher 5-year survival rates in positive expression
      groups when compared with that of negative expression groups (P < 0.05 and P <
      0.01). (3) The univariate analysis showed: histology grade, status of cervical
      lymph node, clinical stage, T stage, recurrence, Skp2 expression, p27 expression,
      E-cad expression and alpha-cat expression were proven to significant (P < 0.05);
      Multivariate analysis showed: Skp2 expression, alpha-cat expression and
      recurrence were independent prognostic factors of survival of LSCC patients (P <
      0.05). (4) Skp 2 expression was inversely associated with p27 expression, p27
      expression was significantly associated with alpha-cat expression, E-cad
      expression was significantly associated with alpha-cat expression. CONCLUSION:
      The chief prognostic factors of survival of LSCC patients were Skp2 expression,
      alpha-cat expression and recurrence.

PMID- 17017187
TI  - [The value of 99mTc-DX105 cervical lymphatic imaging in detecting cervical lymph
      node metastasis of laryngeal and hypopharyngeal carcinoma].
AB  - OBJECTIVE: To study the value of single photon emission-computed tomography
      (SPECT) lymphatic imaging by percutaneous injection of 99mTc-DX105 in detecting
      cervical lymph node metastasis of laryngeal and hypopharyngeal carcinoma. METHOD:
      One-three days before the operation, 185MBq 99mTc-DX105 was injected via
      bilateral mastoids portion percutaneously in each of 30 patients with laryngeal
      and hypopharyngeal carcinoma, and thus SPECT lymphatic imaging was conducted.
      Then, the diagnostic result was compared with those of pathological examination
      of neck dissection specimens. RESULT: In SPECT lymphatic imaging of 53 sides neck
      of 30 patients, 24 sides cervical lymph node were positive, and 3 sides were
      false positive; 29 sides cervical lymph node were negative, and 1 side was false
      negative, Sensitivity, specificity and accuracy of SPECT lymphatic imaging were
      95.5% (21/22), 90.3% (28/31) and 92.5% (49/53) respectively. Among the 8 sides
      cervical lymph node metastasis which were false negative by clinical palpation, 7
      sides were positive by SPECT lymphatic imaging. CONCLUSION: It is suggested that
      SPECT lymphatic imaging by percutaneous injection of 99mTc-DX105 in detecting
      cervical lymph node metastasis of laryngeal and hypopharyngeal carcinoma is
      pretty valuable for guiding clinical neck node dissection.

PMID- 17017188
TI  - [Study on the myoelectric activity of dilatation muscles of upper airway in
      patients with obstructive sleep apnea-hypopnea syndrome under asleep condition].
AB  - OBJECTIVE: To observe the changes of the electromyography(EMG) of the dilatation
      muscles of upper airway in patients with obstructive sleep apnea-hypopnea
      syndrome (OSAHS) under asleep condition and to explore their functions and
      significance. METHOD: The myoelectronic activity of levator palatini muscle,
      tensor palatini muscle, genioglossus muscle was measured by ENG in patients with
      moderate to serious OSAHS before and after induction of sleep and was compared
      with normal control. RESULT: (1) The myoelectronic activity of dilation muscles
      of the upper airway in OSAHS patients were higher than that in control under
      awake condition (P < 0.01). (2) When the patients were asleep, the myoelectronic
      activity of these muscles dropped significantly (P < 0.01). (3) The decrease of
      myoelectronic activity of dilatation muscles of upper airway was more dramatic in
      patients with OSAHS than that in control when turned from awake condition to
      asleep condition (P < 0.01). CONCLUSION: The compensative raise of myoelectronic
      activity of dilatation muscles of upper airway under awake condition and the
      decompensation when asleep in patients with OSAHS were important in the
      pathogenesis.

PMID- 17017189
TI  - [Analysis on the long-term curative effect of endoscopic sinus surgery].
AB  - OBJECTIVE: To analyze the long-term curative effect of endoscopic sinus surgery.
      METHOD: One hundred and twenty-eight cases (180 sides) of chronic sinusitis and
      nasal polyps were treated with FESS, 80 side (64 cases) were elected randomly to
      deal with the anatomical variation of middle and inferior turbinate and nasal
      septum during the operation (rectification group), comparing the curative effects
      with other 100 sides (64 cases) (contrast group). RESULT: Following up survey
      from 12 months to 24 months postoperatively, the curative effect in the
      rectification group was better than that in the contrast group. CONCLUSION:
      Dealing with anatomical variation that influence the nasal cavity function in
      FESS can significantly improve the healing rate of sinusitis and ventilation
      function and decrease the adhesions rate.

PMID- 17017190
TI  - [Serum angiogenin concentration in nasopharyngeal carcinoma patients and its
      clinical significance].
AB  - OBJECTIVE: To determine the serum angiogenin (ANG) concentration in patients with
      nasopharyngeal carcinoma (NPC) and analyze its clinical significance. METHOD:
      Forty-two NPC patients and 30 healthy controls entered this study. Serum ANG
      level was quantitatively analyzed by enzyme-linked immunosorbent assay (ELISA).
      RESULT: The mean level of serum ANG in untreated NPC was (371.4 +/- 123.5)
      microg/L, which was significantly higher than that in healthy controls(292.5 +/-
      74.2) microg/L (P < 0.01). Furthermore, the serum level of ANG increased with the
      development of tumor (P < 0.05). After treatment, all patients reached a
      response: partial response (PR) or complete response (PR), and the serum ANG
      level was (340.6 +/- 112.4) microg/L, which was significantly lower than that in
      untreated ones (P < 0.05), but still higher than that in healthy controls (P <
      0.05). CONCLUSION: Our results indicate that the serum ANG level increases in
      patients with NPC, and is correlate with primary tumor progression.

PMID- 17017191
TI  - [Expression of androgen receptor and estrogen receptor in carcinoma of larynx].
AB  - OBJECTIVE: To study the expressions of androgen receptor (AR) and estrogen
      receptor (ER) in the pathogenesis of laryngeal carcinoma. METHOD: The method of
      in situ hybridization was employed to detect the expressions of AR and ER in 63
      specimens of laryngeal carcinoma, 20 specimens of normal tissue beside carcinoma
      and 20 specimens of laryngeal benign lesion. RESULT: The expressions of AR and ER
      in specimens of normal tissue and laryngeal benign lesion were negative. The
      expressions of AR in laryngeal carcinomas was 68.3%, the expressions of ER was
      69.8%, which was not correlated with sex and clinical classification (P > 0.05).
      With the differentiation of pathologic-classify and clinical stage, the
      expressions of AR in carcinoma of larynx were significantly increased, but ER was
      opposite (P < 0.05). The expression of AR was observed more frequently in
      patients with lymph node metastasis, but the expression of ER was degraded (P <
      0.05). Compared with carcinoma of larynx, the expressions of AR and ER in
      specimens of normal tissue laryngeal benign lesion were significantly different
      (P < 0.01). CONCLUSION: The expressions of sex hormone acceptor are concerned
      with the incidence of carcinoma of larynx. The expressions of AR and ER are
      closely related to pathologic-classify, clinical stage and lymph node metastasis.
      AR promoted the growth of laryngeal carcinoma, but ER restrained it. AR and ER
      could be marked to understand malignant degree and prognosis, but they were not
      correlated with sex and clinical classification. The difference in expression of
      AR and ER does not explain the difference of sex and incidence of laryngeal
      carcinoma difference in expression of AR and ER, it shows that the significant
      difference of sex in the incidence of carcinoma of larynx may be concerned with
      other factors.

PMID- 17017192
TI  - [The effect of cervical gas insufflation on metabolic and hemodynamic during
      endoscopic neck surgery].
AB  - OBJECTIVE: Carbon dioxide and helium were insufflated into the neck of rabbits to
      investigate the effect of different levels of insufflation pressure and duration
      on metabolic and hemodynamic changes. METHOD: Fifteen New Zealand rabbits were
      randomly divided into 5 groups: 5 mmHg CO2, 10 mmHg CO2, 15 mmHg CO2, 15 mmHg He
      and 0 mmHg. Arterial partial pressure of CO2 (PaCO2), pH, heart rate (HR), mean
      arterial pressure (MAP) and central venous pressure (CVP) were measured at
      baseline, 45 min and 90 min after gas insufflation and 30 min after desufflation.
      RESULT: Insufflation of CO2 at 5 mmHg had not any significant effect on the
      parameters. PaCO2 increased significantly 45 min and 90 min after CO2
      insufflation at 10 mmHg (P < 0.05). Marked changes in PaCO2, pH and CVP occurred
      45 min and 90 min after CO2 insufflation at 15 mmHg (P < 0.05), and the
      parameters did not return to baseline 30 min after desufflation. In animals
      receiving He insufflation at 15 mmHg, CVP increased significantly after 90 min (P
      < 0.05), and the parameters returned to baseline 30 min after desufflation.
      Animals receiving He insufflation did not experience hypercapnia. No significant
      changes in HR and MAP occurred in all animals. CONCLUSION: Carbon dioxide
      insufflation for endoscopic neck surgery is safe below 10 mmHg. When higher
      pressure is required, the level lower than 15 mmHg is recommended and the
      insufflation duration should be limited. The use of He should be careful due to
      the low solubility.

PMID- 17017193
TI  - [Isolation and culture of neural stem cell from rat olfactory epithelium].
AB  - OBJECTIVE: To isolate and culture neural stem cell (NSC) from rat olfactory
      epithelium and investigate the characteristics of its proliferation and
      differentiation. METHOD: NSC from postnatal three-day (P3) and zinc sulfate in
      situ injured adult rat olfactory epithelium was cultured with DMEM/F12 (1 : 1)
      containing 10% heat-inactivated fetal bovine serum. NSC and specific neural cells
      differentiated from NSC were identified with indirect immunofluorescence. Growth
      curve of NSC from P3 and adult rat and the effect of growth factors were measured
      using MTT method. RESULT: Neurosphere-forming cells were isolated and collected
      with diluted purification method from P3 and adult rat olfactory epithelium.
      These neurosphere-forming cells were nestin immuno-positive and cytokeratin
      immuno-negative, and could differentiated into neuronal specific enolase (NSE)
      immuno-positive neurons and glial fibrillary acidic protein (GFAP) immuno
      positive astrocytes when transferred in MEM. The viability of NSC had no
      significant difference between P3 and adult rat (P > 0.05). The forming rate of
      neurosphere of P3 and adult rat olfactory epithelium was 0.05% - 0.10%.
      Fibroblast growth factor-basic could significantly promote the proliferation of
      NSC from epithelium, while epidermal growth factor showed no effect on the
      proliferation of the NSC. CONCLUSION: NSC with self-renewal capacity and
      multipotential differentiation can be isolated and cultured from P3 and adult rat
      olfactory epithelium.

PMID- 17017195
TI  - Pars plana vitrectomy: comparison of three techniques for the treatment of
      diabetic vitreous hemorrhage.
AB  - BACKGROUND AND OBJECTIVE: To compare the outcome of three vitrectomy techniques
      in the treatment of diabetic vitreous hemorrhage. PATIENTS AND METHODS: The study
      group included 38 patients (38 eyes) with diabetic vitreous hemorrhage. Three
      port pars plana vitrectomy was used in 20 eyes, unimanual vitrectomy with
      indirect ophthalmoscopy in 10 eyes, and sutureless 25-gauge vitrectomy in 8 eyes.
      Main outcome measures were operative time, preoperative and postoperative visual
      acuity and intraocular pressure, and postoperative complications. RESULTS: Mean
      operative time was 66 minutes for three-port vitrectomy, 35 minutes for indirect
      vitrectomy, and 40 minutes for 25-gauge vitrectomy. Mean duration of follow-up
      was 26 months (range = 5 to 43 months). All three techniques successfully treated
      the vitreous hemorrhage, with similar best-corrected visual acuity outcome and
      similar complication rates. A greater tendency for hypotony on the first
      postoperative day was observed in the 25-gauge vitrectomy group. CONCLUSIONS: The
      three major techniques for treating vitreous hemorrhage are similarly effective
      and yield similar outcomes. The specific technique used should be selected on the
      basis of the clinical status of the patient and the skills of the surgeon.

PMID- 17017194
TI  - ICG angiography-guided photodynamic therapy for large pigment epithelial
      detachments in age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the role of photodynamic therapy (PDT) in
      the management of vascularized pigment epithelial detachment in age-related
      macular degeneration (AMD) when the pigment epithelial detachment is the
      predominant component of the neovascular complex. PATIENTS AND METHODS: Seventeen
      eyes of 17 patients underwent indocyanine green angiography-guided PDT and had at
      least 6 months of follow-up. Data retrieved included visual acuity and
      angiographic features prior to the treatment, number of PDT sessions, visual
      acuity, angiographic outcomes at the end of the follow-up, length of follow-up,
      and status of the fellow eye. in the series, with an average age of 77 years and
      a mean follow-up time of 11 months. Six (35%) of the patients lost less than 3
      lines of visual acuity, 6 (35%) lost between 3 and 6 lines, and 5 (30%) lost 6 or
      more lines. Angiographic outcomes were categorized as failures in 14 (82%) of the
      treated eyes and successful in 3 (17%) eyes. CONCLUSIONS: In 82% of the eyes, PDT
      failed to flatten the pigment epithelial detachment or prevent growth of the
      choroidal neovascular membrane. Visual acuity outcomes correlated poorly with
      angiographic outcomes. PDT does not seem to improve the prognosis of eyes with
      large pigment epithelial detachments in AMD.

PMID- 17017196
TI  - Serial optical coherence tomography of subthreshold diode laser micropulse
      photocoagulation for diabetic macular edema.
AB  - BACKGROUND AND OBJECTIVE: To use serial optical coherence tomography (OCT) to
      evaluate low-intensity, high-density subthreshold diode laser micropulse
      photocoagulation treatment of clinically significant diabetic macular edema.
      PATIENTS AND METHODS: Eighteen consecutive eyes of 14 patients with clinically
      significant diabetic macular edema and a minimum foveal thickness of 223 microm
      or greater were prospectively evaluated by OCT preoperatively and 1, 4, and 12
      weeks following treatment. RESULTS: Overall, estimated macular edema 3 months
      postoperatively (minimum foveal thickness--223 microm) was reduced a mean of 24%
      (P = .02). Eleven eyes treated for recurrent or persistent clinically significant
      diabetic macular edema following prior treatment more than 3 months before study
      entry were most improved, with a mean reduction in estimated macular edema 3
      months postoperatively of 59%. No treatment complications were observed. No
      patient demonstrated laser lesions following treatment. CONCLUSIONS: Low
      intensity, high-density subthreshold diode laser micropulse photocoagulation can
      reduce or eliminate clinically significant diabetic macular edema measured by
      OCT. Further study is warranted.

PMID- 17017197
TI  - Ultrastructural study of autologous cultivated conjunctival epithelium.
AB  - BACKGROUND AND OBJECTIVE: This report is one of the first in the literature on
      the attempted cultivation and clinical application of human conjunctival
      epithelium. The authors investigated the possibility of restoring severely
      damaged ocular surface with autologous cultivated conjunctival epithelium.
      PATIENTS AND METHODS: The conjunctival cells needed for the experiment were
      harvested from six patients with oculopalpebral diseases. Confluent epithelial
      sheets were developed from each biopsy specimen. The new epithelium was then
      implanted on the patients' or donors' eye surface. RESULTS: The histologic
      examination showed a pluristratified squamous non-keratinized epithelium lying on
      a basement membrane and with a lamina propria of well-vascularized connective
      tissue. Normal ultrastructural characteristics were evident on electron
      microscopy. CONCLUSION: The cultivation of autologous conjunctival cells may be a
      good option for rapid and safe repair of large single or bilateral conjunctival
      defects, as an alternative to heterotopic or allogenic grafts.

PMID- 17017198
TI  - Teaching and assessing surgical competency in ophthalmology training programs.
AB  - BACKGROUND AND OBJECTIVE: The Accreditation Council for Graduate Medical
      Education (ACGME) has mandated implementation of six new competencies in resident
      training in the United States. An implementation strategy is proposed to teach
      and assess cataract surgical competence. PATIENTS AND METHODS: An
      intradepartmental Task Force for the ACGME competencies reviewed the literature
      for assessment tools to develop an implementation matrix for assessing surgical
      competence. RESULTS: "Good practices" (gleaned from the literature) were adapted
      for the institution's needs and tested, including (1) written and explicit goals
      or objectives for each stage of training; (2) substitution of a criterion
      referenced (Dreyfus model) scoring rubric for a norm-referenced, peer-benchmarked
      global evaluation; (3) use of formative rather than summative feedback; (4)
      incorporation of deliberate practice (Ericsson model); and (5) portfolio-based
      documentation of sentinel event markers and remediation. CONCLUSION: An
      implementation matrix for teaching and assessing surgical competence might be
      useful for local compliance with the ACGME mandate.

PMID- 17017199
TI  - Efficacy of laser trabeculoplasty in phakic and pseudophakic patients with
      primary open-angle glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To compare the efficacy of laser trabeculoplasty in
      pseudophakic and phakic patients with primary open-angle glaucoma (POAG).
      PATIENTS AND METHODS: Retrospective comparative case-control series of 42 eyes
      (21 pseudophakic eyes and 21 phakic eyes of patients matched for age and gender)
      with POAG not controlled using medical therapy and treated with laser
      trabeculoplasty. Success was reduction of intraocular pressure (IOP) of at least
      3 mm Hg from baseline and no additional glaucoma surgery or laser treatment.
      uloplasty, there was no significant difference between pseudophakic and phakic
      eyes in the mean IOP and change from baseline IOP Success at 12 months was 78%
      for pseudophakic and 80% for phakic eyes. Kaplan-Meier survival analysis showed
      no statistically significant difference in success after laser trabeculoplasty
      comparing phakic to pseudophakic eyes (P = .87). CONCLUSION: In eyes with POAG,
      laser trabeculoplasty is as effective in pseudophakic eyes as in phakic eyes.

PMID- 17017200
TI  - Fundus autofluorescence before and after photodynamic therapy for choroidal
      neovascularization secondary to age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To describe fundus autofluorescence patterns in
      choroidal neovascularization secondary to age-related macular degeneration before
      and after photodynamic therapy (PDT). PATIENTS AND METHODS: Sixty-eight
      consecutive eyes were indicated for PDT after standard fluorescein angiography,
      which showed completely classic choroidal neovascularization (CNV) (n=52), occult
      with no classic CNV (n=7), and predominantly classic CNV (n=9). Standardized PDT
      was performed and patients were examined 2 to 3 months later. Angiography and
      autofluorescence measurements were performed again and compared with preoperative
      values. RESULTS: At baseline, autofluorescence was mainly decreased in areas of
      completely classic CNV (79%), but showed a regular or mottled pattern in occult
      CNV. A slightly increased (50%) or normal (50%) autofluorescence was seen at the
      rim of the classic lesions within the junctional zone. Membrane demarcation was
      improved (90%) in classic membranes 2 to 3 months after PDT. After PDT for occult
      membranes, a transformation into classic membranes with residual leakage and need
      for further PDT was observed (6 of 7 eyes), showing the described
      autofluorescence patterns. For the mixed type of CNV, both described patterns of
      autofluorescence distribution were found. CONCLUSION: Especially classic CNVs
      reveal distinct characteristics of significantly decreased autofluorescence,
      presumably due to their localization above the retinal pigment epithelium level,
      leading to blockage of autofluorescence. Autofluorescence patterns after PDT
      included enhanced demarcation of the membrane, suggesting reactive retinal
      pigment epithelial changes. Autofluorescence might be an interesting tool to
      distinguish noninvasively between classic and occult CNV in age-related macular
      degeneration and to monitor changes after PDT.

PMID- 17017201
TI  - Angiographic effects of indocyanine green photobleaching by the diode laser.
AB  - BACKGROUND AND OBJECTIVE: To investigate the cause of hypofluorescent spots
      detected by indocyanine green (ICG) videoangiography in areas subjected to ICG
      enhanced transpupillary thermotherapy in pigmented rabbits. MATERIALS AND
      METHODS: In 6 eyes, two similar areas were treated with transpupillary
      thermotherapy. A standard dose of ICG (0.5 mg/kg) was injected intravenously
      before treatment of the second area. Red-free photographs without further
      injection of ICG (first ICG videoangiography) were then performed. The first area
      was re-irradiated using the same parameters. Red-free photographs and a second
      ICG videoangiography, still without further injection of ICG, were performed. ICG
      was then re-injected and a third ICG videoangiography was obtained. Finally,
      fluorescein angiography was performed. RESULTS: The first ICG videoangiography
      demonstrated hyperfluorescence of the first area and normofluorescence of the
      second area. The second ICG videoangiography demonstrated hypofluorescence of the
      first area. The third ICG videoangiography showed hyperfluorescence of both
      areas. CONCLUSIONS: Hypofluorescence detected after re-irradiation is probably
      related to ICG photobleaching.

PMID- 17017202
TI  - Bilateral CRAO and CRVO from thrombotic thrombocytopenic purpura: OCT findings
      and treatment with triamcinolone acetonide and bevacizumab.
AB  - A patient with thrombotic thrombocytopenic purpura secondary to adult-onset
      Still's disease presented with bilateral combined central retinal artery
      occlusion and central retinal vein occlusion, a rare complication reported only
      once before. Fundus appearance and fluorescein angiography were similar to the
      previous case. Optical coherence tomography findings demonstrated aspects
      consistent with both central retinal artery occlusion and central retinal vein
      occlusion. Treatment of one eye with intravitreal triamcinolone acetonide (4 mg)
      was not effective in improving visual acuity. Treatment of both eyes with
      intravitreal bevacizumab (1.25 mg) and panretinal photocoagulation was effective
      in eliminating iris neovascularization, although the patient lost all visual
      function.

PMID- 17017203
TI  - Macular hole formation following thermal laser photocoagulation in a patient with
      choroidal neovascular membrane and age-related macular degeneration.
AB  - A woman with age-related macular degeneration and an extrafoveal choroidal
      neovascularization was treated with thermal laser photocoagulation. Three years
      later, an optical coherence tomography image showed a full-thickness macular hole
      with some contracture toward the adjacent atrophic laser scar, suggestive of some
      presumptive tangential forces.

PMID- 17017204
TI  - Photodynamic therapy with verteporfin for juxtafoveal choroidal
      neovascularization in serpiginous choroiditis.
AB  - The authors describe a patient who underwent successful photodynamic therapy with
      verteporfin for juxtafoveal choroidal neovascularization complicated by
      serpiginous choroiditis. A 41-year-old woman presented with decreased vision and
      metamorphopsia in her right eye, which was diagnosed as a recurrence of
      serpiginous choroiditis at the first visit. Within a month, visual acuity had
      diminished to 20/1000 despite immunosuppressive treatment. At that time,
      indocyanine green angiography and optical coherence tomography revealed choroidal
      neovascularization in the juxtafoveal area. Photodynamic therapy with verteporfin
      was administered twice, after which juxtafoveal choroidal neovascularization
      regressed and her visual acuity improved to 20/20.

PMID- 17017205
TI  - Syphilitic retinitis with focal inflammatory accumulations.
AB  - A 42-year-old man with a history of human immunodeficiency virus and previous
      immune reconstitution after initiating a highly active antiretroviral therapy
      regimen was referred to rule out cytomegalo-virus retinitis. He had an unusual
      juxtapapillary collection of white superficial material and multiple preretinal
      collections resting on a peripheral ground glass opacification of the retina.
      These lesions quickly resolved after initiating treatment for syphilitic
      retinitis. The patient appeared to have developed an exaggerated response to the
      ocular syphilitic infection that may be related to the augmentation of his
      impaired immune system by highly active antiretroviral therapy.

PMID- 17017206
TI  - Hyphema occurring during selective laser trabeculoplasty.
AB  - The first case of hyphema occurring during selective laser trabeculoplasty in an
      eye without neovascularization is described. A 77-year-old man with uncontrolled
      open-angle glaucoma received selective laser trabeculoplasty in both eyes for
      high intraocular pressure with maximally tolerated medical treatment. Hyphema
      occurred during selective laser trabeculoplasty in the left eye. This resolved
      spontaneously without sequelae. Successful intraocular pressure control was
      achieved. Hyphema and bleeding can happen during selective laser trabeculoplasty.
      Although this was transient and uneventful in one patient, careful monitoring of
      intraocular pressure and anterior chamber reaction is advised.

PMID- 17017207
TI  - A new surgical technique for anterior segment ectasia: tectonic lamellar
      sclerokeratoplasty.
AB  - A 41-year-old patient with severe anterior segment ectasia and a previous history
      of failed corneal graft was treated by placing a 14-mm tectonic corneoscleral
      allograft in the eye to support both the corneal and the scleral thinning. Nylon
      10-0 interrupted sutures were used at the sclero-scleral junction. The host
      conjunctiva, including the limbal area, was carefully sutured to the donor limbal
      area. Three months postoperatively, the graft was stable with no progression of
      the ectasia. The suturing of a corneoscleral graft over a severely ectatic cornea
      may be an acceptable technique for providing tectonic tissue support and
      stabilizing eyes with severe anterior segment ectasia.

PMID- 17017208
TI  - Cyclodialysis and hypotony maculopathy.

PMID- 17017209
TI  - Bartonella quintana, lice, and molecular tools.

PMID- 17017210
TI  - Ticks (Acari: Ixodidae) associated with wildlife and vegetation of Haller park
      along the Kenyan coastline.
AB  - This artcile describes the results obtained from a tick survey conducted in
      Haller park along the Kenyan coastline. The survey aimed at evaluating tick-host
      associations, assessing tick population density, and providing baseline
      information for planning future tick control and management in the park. Ticks
      (2,968) were collected by handpicking from eight species of wildlife and by
      dragging in 14 selected sites within the park. A considerable proportion of ticks
      were also collected from leaves, stems, and bark of most dominant trees, namely,
      Casuarina equisetifolia L. (Forst. and Forst.), Cocos nucifera L., Adansonia
      digitata L., Musa paradisiaca L., and Azadiracta indica Adr. Juss. Dragging was
      conducted in sites predominantly occupied by Cynodon dactylon L. (Pers.),
      Cenchrus ciliaris L., Stenotaphrum dimidiatum L. (Kuntze.) Brongn., and
      Brachiaria xantholeuca Hack. Ex Schinz Stapf. and Loudetia kagerensis K. Schum.
      Hutch. Eight tick species were identified, and the collection included
      Rhipicephalus pravus Donitz 1910, Rhipicephalus pulchellus Gerstacker 1873,
      Hyalomma marginatum rufipes Koch 1844, Amblyomma gemma Donitz 1910, Amblyomma
      hebraeum Koch 1844, Amblyomma sparsum Neumann 1899, Amblyomma nuttalli Donitz
      1909, and Boophilus decoloratus Koch 1844. Given that the identified tick species
      are known to parasitize humans as well as livestock, there exist risks of
      emergence of zoonotic infections mediated by tick vectors. In the recreational
      environment of Haller park, where tick vectors share habitats with hosts, there
      is a need to develop sustainable and effective tick control and management
      strategies to minimize economic losses that tick infestation may cause.

PMID- 17017211
TI  - Origin of pitcher plant mosquitoes in Aedes (Stegomyia): a molecular phylogenetic
      analysis using mitochondrial and nuclear gene sequences.
AB  - Two mosquito species of the subgenus Stegomyia (genus Aedes) (Diptera: Culicidae)
      on the islands of Palau and Yap (Aedes dybasi Bohart and Aedes maehleri Bohart)
      are adapted to aquatic habitats occupied by Nepenthes pitcher plants. To reveal
      the origin of these pitcher plant mosquitoes, we attempted a molecular
      phylogenetic analysis with 11 Stegomyia species by using sequence data from
      mitochondrial cytochrome oxidase subunit I and 16SrRNA genes as well as the
      nuclear 28SrRNA gene. Ae. dybasi, a pitcher plant specialist, was sister to Aedes
      palauensis Bohart within the scutellaris group from the same islands. Ae.
      maehleri, an opportunistic pitcher plant mosquito, was in a distinct lineage
      related to the scutellaris group. The adaptation to pitcher plants could have
      occurred independently in these two species, and recent differentiation of the
      pitcher plant mosquito Ae. dybasi from the nonpitcher plant mosquito Ae.
      palauensis was suggested by a relatively small sequence divergence between these
      species. We also discuss the implications of this analysis for the phylogeny of
      some other Stegomyia species.

PMID- 17017212
TI  - Notes on New World Persicargas ticks (Acari: Argasidae) with description of
      female Argas (P.) keiransi.
AB  - The female of Argas (Persicargas) keiransi Estrada-Pena, Venzal & Gonzalez-Acuna
      (Acari: Argasidae) is described from specimens collected in the type locality in
      Chile. The female has a unique combination of characters in the dorsal cuticle
      and in the number and pattern of ventrolateral setae in the basis capituli.
      Additional features on tarsus I chaetotaxy and dorsal plate are provided for the
      larva of the species, as observed on flat specimens derived from engorged females
      collected in the type locality. Keys for the larvae of the New World Persicargas
      are provided as well as illustrations for prominent characters in hypostome and
      posterolateral setae. The mitochondrial 16S rDNA sequence of A. keiransi has been
      obtained, and an analysis of the phylogenetic relationships with other ticks is
      included. Phylogenetic analysis provides support for a Persicargas grouping of
      species, separated from species in Argas.

PMID- 17017213
TI  - County-level surveillance of white-tailed deer infestation by Ixodes scapularis
      and Dermacentor albipictus (Acari: Ixodidae) along the Illinois River.
AB  - From 1998 to 2003, 4,935 hunter-killed deer in northern and central Illinois were
      examined for ticks; 4,066 blacklegged ticks, Ixodes scapularis Say, and 6,530
      winter ticks, Dermacentor albipictus (Packard) (Acari: Ixodidae), were collected.
      I. scapularis was the predominant tick species in the northern portion of the
      study area, with a decreasing north-to-south prevalence gradient. In contrast, D.
      albipictus was more common in the south with a decreasing south-to-north
      prevalence gradient. Compared with previous studies, the geographic range for
      both species expanded into the central portion of the Illinois River. Prevalence
      and intensity of both tick species were greater on bucks, and infested bucks were
      geographically more widespread than infested does and fawns. These findings
      indicate that blacklegged tick and winter tick distributions remain dynamic in
      the north central United States

PMID- 17017215
TI  - Effects of rice straw and water management on riceland mosquitoes.
AB  - Rice fields are important sources of mosquitoes in many regions, and rice (Oryza
      spp.) growing practices can affect mosquito populations. Rice straw incorporation
      and winter flooding have become common methods to prepare seedbeds, largely
      replacing burning of straw. These methods increase nutrients during the growing
      season. We sampled mosquito larvae during 1999-2001 in 16 0.72-ha plots where
      straw was either burned or incorporated into soil after the previous growing
      season; these treatments were crossed with either winter flooding or no winter
      flooding. In 2000, all fields were drained mid-season for an application of
      herbicide, and then they were reflooded. Mosquitoes responded positively to straw
      incorporation and winter flooding, especially in combination. The mid-season
      reflood in year 2 was associated with an order of magnitude increase in Culex
      tarsalis Coquillett larvae. Results confirm that rice straw and water management
      can strongly influence mosquito populations.

PMID- 17017214
TI  - Is vector body size the key to reduced malaria transmission in the irrigated
      region of Niono, Mali?
AB  - Malaria vectors can reach very high densities in villages near irrigated rice
      fields in Africa, leading to the expectation that malaria should be especially
      prevalent there. Surprisingly, this is not always the case. In Niono, Mali,
      villages from nonirrigated areas have higher malaria prevalence than those within
      the irrigated regions, which suffer from higher mosquito numbers. One hypothesis
      explaining this observation is that mosquitoes from irrigated fields with high
      densities are inefficient vectors. This could occur if higher larval densities
      lead to smaller mosquitoes that suffer elevated mortality. Three predictions of
      the hypothesis were studied. First, the effect of larval density on larval body
      size was measured for both Anopheles gambiae Giles and Anopheles funestus Giles.
      Second, the relationship between larval and adult body size was tested. Third,
      evidence of an effect of adult size on survivorship in both irrigated and
      nonirrigated villages during the wet and dry seasons was sought. There was a
      modest positive relationship between densities of immatures and larval size, and
      a strong relationship between larval and adult size. Furthermore, adult
      survivorship was higher in nonirrigated areas. However, there was no effect of
      size on survivorship between comparable samples from both the irrigated and
      nonirrigated zones. Although density may have a causal relationship with reduced
      transmission in the irrigated areas of Niono, it is unlikely to be because higher
      density leads to smaller body size and lower survivorship.

PMID- 17017216
TI  - Reproductive output of female Anopheles gambiae (Diptera: Culicidae): comparison
      of molecular forms.
AB  - Knowledge of ecological differences between the molecular forms of Anopheles
      gambiae Giles (Diptera: Culicidae) might lead to understanding of their unique
      contribution to disease transmission, to better vector control, and to
      identification of the forces that have separated them. We compared female
      fecundity measured as egg batch size in relation to body size between the
      molecular forms in Mali and contrasted them with their sibling species, Anopheles
      arabiensis Patton. To determine whether eggs of different egg batches are of
      similar "quality," we compared the total protein content of first-stage larvae
      (L1s), collected < 2 h after hatching in deionized water. Egg batch size
      significantly varied between An. gambiae and An. arabiensis and between the
      molecular forms of An. gambiae (mean batch size was 186.3, 182.5, and 162.0 eggs
      in An. arabiensis and the M and the S molecular form of An. gambiae,
      respectively). After accommodating female body size, however, the difference in
      batch size was not significant. In the S molecular form, egg protein content was
      not correlated with egg batch size (r = -0.08, P > 0.7) nor with female body size
      (r = -0.18, P > 0.4), suggesting that females with more resources invest in more
      eggs rather than in higher quality eggs. The mean total protein in eggs of the M
      form (0.407 microg per L1) was 6% higher than that of the S form (0.384 microg
      per L1), indicating that the M form invests a greater portion of her resources
      into current (rather than future) reproduction. A greater investment per
      offspring coupled with larger egg batch size may reflect an adaptation of the M
      form to low productivity larval sites as independent evidence suggests.

PMID- 17017217
TI  - Abundance and species composition of Culicoides (Diptera: Ceratopogonidae) at
      cattle facilities in southern Alberta, Canada.
AB  - Culicoides fauna was examined at seven feedlots and one rangeland site (Warner)
      in southern Alberta, Canada, during a 3-yr period. Eight species and species
      groups accounted for > 99% of the Culicoides (Diptera: Ceratopogonidae) captured.
      The most abundant species or groups were Culicoides gigas Root and Hoffman,
      Culicoides sonorensis (Wirth and Jones), Culicoides (Selfia) group, and
      Culicoides palmerae group. These accounted for 78-88% of the Culicoides captured,
      with the balance being members of the Culicoides cockerellii section, Culicoides
      crepuscularis Malloch, Culicoides wisconsinensis Jones, and Culicoides yukonensis
      Hoffman. Univariate and multivariate analyses indicated that the rangeland site
      was characterized by greater abundance of C. sonorensis and C. palmerae and lower
      abundance of C. (Selfia) compared with the feedlot sites. The Culicoides fauna
      was more dissimilar among sites as geographic distance between sites increased.
      Species of Culicoides captured in this study showed three broad patterns of
      seasonal abundance. The C. palmerae group had the earliest seasonal activity,
      with an increase in June, peak in July, and greatly reduced abundance thereafter.
      C. crepuscularis, C. (Selfia), C. wisconsinensis, and C. gigas had later periods
      of activity, with peak abundance in July, but moderate abundance in June and
      August. C. cockerellii, C. yukonensis, and C. sonorensis had the latest periods
      of activity, with populations increasing through June and July, peaking in
      August, and declining thereafter. C. sonorensis was somewhat unique on that it
      was the only species with moderate abundance as late as September.

PMID- 17017218
TI  - Effect of La Crosse virus infection on insemination rates in female Aedes
      triseriatus (Diptera: Culicidae).
AB  - Aedes triseriatus (Say) (Diptera: Culicidae) females orally infected with La
      Crosse virus after ingesting an infectious bloodmeal were compared for mating
      efficiency with females that ingested a noninfectious bloodmeal. After 14-d
      extrinsic incubation to allow for dissemination of the infection, all females
      were offered a second noninfectious bloodmeal and were placed in cages with age
      matched males for 5 d. After 6 d, insemination rates were determined by detection
      of sperm in the spermathecae. Insemination rates of the La Crosse virus-infected
      females were significantly greater than in uninfected females.

PMID- 17017219
TI  - Genetic and morphometric evidence for population isolation of Glossina palpalis
      gambiensis (Diptera: Glossinidae) on the Loos islands, Guinea.
AB  - Allele frequencies at four microsatellite loci, and morphometric features based
      on 11 wing landmarks, were compared among three populations of Glossina palpalis
      gambiensis (Diptera: Glossinidae) in Guinea. One population originated from the
      Loos islands separated from the capital Conakry by 5 km of sea, and the two
      others originated from the continental mangrove area close to Dubreka, these two
      groups being separated by approximately 30 km. Microsatellites and wing geometry
      data both converged to the idea of a separation of the Loos island population
      from those of the mangrove area. Although occasional contacts cannot be excluded,
      our results support the hypothesis of the Loos population of tsetse flies being a
      completely isolated population. This situation will favor a sequenced
      intervention against human African trypanosomosis and the possibility of an
      elimination of tsetse from this island.

PMID- 17017220
TI  - A standard cytogenetic photomap for the mosquito Anopheles stephensi (Diptera:
      Culicidae): application for physical mapping.
AB  - To facilitate physical genome mapping, we have developed a new cytogenetic
      photomap for Anopheles stephensi (Liston) (Diptera: Culicidae), an important
      malaria vector in Asia. The high-resolution images of the ovarian polytene
      chromosomes have been straightened and divided by numbered divisions and lettered
      subdivisions. The exact chromosomal locations of eight DNA probes have been
      determined by fluorescent in situ hybridization. Using the DNA sequences, we have
      established correspondence between chromosomal arms among An. stephensi,
      Anopheles gambiae (Patton), and Anopheles funestus (Giles). The results support
      previous cytogenetic observations of arm translocations taking place during
      diversification of the species. To make the cytogenetic map useful for population
      genetics studies, we have indicated the chromosomal positions for the breakpoints
      of 19 polymorphic inversions.

PMID- 17017221
TI  - A glycine- and glutamate-rich protein is female salivary gland-specific and
      abundant in the malaria vector Anopheles dirus B (Diptera: Culicidae).
AB  - Before transmission, malaria parasites reside in the salivary glands of their
      female mosquito hosts. Saliva proteins assist in blood feeding and also may
      influence the ability of mosquitoes to transmit malaria. We attempted to identify
      and isolate cDNAs encoding proteins expressed at a high level in the salivary
      glands of a malaria vector, Anopheles dirus B Peyton and Harrison (= An. cracens)
      (Diptera: Culicidae). A major protein with an estimated molecular mass of 35 kDa
      and an isoelectric point (pI) of approximately 4 was detected on a two
      dimensional (2D) gel. Internal peptide sequences of the protein spot showed high
      similarity to sequences present in the conserved C-terminal domain of glycine-
      and glutamate (GE)-rich proteins. A full-length cDNA encoding this protein was
      isolated from a salivary gland cDNA library of female An. dirus B. The cDNA
      encoded a 256-residue protein with a calculated molecular mass of 25.4 kDa and a
      pI of 3.9. BLAST analysis confirmed that it is a member of the GE-rich family.
      Compositional and sequence analysis of this and other family members revealed a
      highly acidic N-terminal region of variable length and low sequence conservation
      and a well conserved C-terminal domain containing 10 identical residues across
      the 13 known members of the gene family in mosquitoes. The An. dirus B GE-rich
      transcript was detected by reverse transcription-polymerase chain reaction (PCR)
      only in the female salivary glands, indicating that this protein is female saliva
      specific. The GE-rich proteins may function as a salivary lubricant to facilitate
      blood feeding.

PMID- 17017222
TI  - Dyeing process may alter the efficacy of insecticide-treated nets.
AB  - The biological efficacy as judged by mortality against Anopheles gambiae s.s. of
      three net samples, one white and two colored, treated with deltamethrin by
      conventional dipping was compared. Efficacy as well as chemical analysis results
      showed that uptake of insecticide by white net material was much higher than by
      colored nets. After a single wash, efficacy of colored nets was reduced
      significantly below 80% mortality, which is the minimum acceptable level for a
      field application. This unexpected result could be because of either low uptake
      of insecticide by colored fibers or high alkalinity on the fibers, resulting from
      the dyeing process (reduction clearing). alpha-Cyanopyrethroids, such as
      deltamethrin, have a low stability in alkaline conditions and rapidly degrade.
      Practical implications of this finding are of primary importance because the
      majority of nets currently purchased by institutional buyers for malaria
      prevention are colored.

PMID- 17017223
TI  - Recent emergence of insensitive acetylcholinesterase in Chinese populations of
      the mosquito Culex pipiens (Diptera: Culicidae).
AB  - Organophosphate/carbamate target resistance has emerged in Culex pipiens L.
      (Diptera: Culicidae), the vector of Wuchereria bancrofti and West Nile virus
      (family Flaviviridae, genus Flavivirus) in China. The insensitive
      acetylcholinesterase was detected in only one of 20 samples collected on a north
      to-south transect. According to previous findings, a unique mutation, G119S in
      the ace-1 gene, explained this high insensitivity. Phylogenetic analysis
      indicates that the mutation G119S recently detected in China results from an
      independent mutation event. The G119S mutation thus occurred at least three times
      independently within the Cx. pipiens complex, once in the temperate (Cx. p.
      pipiens) and twice in the tropical form (Cx. p. quinquefasciatus). Bioassays
      performed with a purified G119S strain indicated that this substitution was
      associated with high levels of resistance to chlorpyrifos, fenitrothion,
      malathion, and parathion, but low levels of resistance to dichlorvos,
      trichlorfon, and fenthion. Hence, it is possible that in China, dichlorvos,
      trichlorfon, and fenthion will still achieve effective control even in the
      presence of the G119S mutation.

PMID- 17017224
TI  - Wash resistance and bioefficacy of Olyset net--a long-lasting insecticide-treated
      mosquito net against malaria vectors and nontarget household pests.
AB  - During recent years, long-lasting insecticide-treated nets (LLINs) have been
      developed to overcome the problems of low retreatment rates, washing, and erratic
      dose of the insecticide resulting in the dilution of efficacy of the conventional
      insecticide-treated mosquito nets. These nets are treated at factory level with
      insecticide either incorporated into or coated around fibers. Olyset net, a
      polyethylene net with 2% permethrin incorporated within fibers, is one type of
      LLIN. Therefore, these nets were evaluated for their wash resistance and
      bioefficacy against malaria vectors Anopheles culicifacies Giles and Anopheles
      fluviatilis James (Diptera: Culicidae) and other nontarget species. Cone bioassay
      tests produced 100% mortality in these two vector species with 3-min exposure.
      Results of the bioassays on washed nets showed 100% mortality in An. fluviatilis
      even after 20 washings, whereas in An. culicifacies 100% mortality up to 11
      washings and 80% mortality up to 20 washings were observed. Cone bioassay tests
      also were performed on nontarget mosquito species Culex quinquefasciatus Say;
      house fly, Musca domestica L.; American cockroach, Periplaneta americana (L.);
      head louse, Pediculus humanus capitis De Geer; and bed bug, Cimex lectularius L.
      with 30-min exposure. Except for bed bugs, 100% mortality was observed in these
      nontarget species after 24-h recovery period. In bed bugs, only 25% mortality was
      observed. The density of An. culicifacies and An. fluviatilis was significantly
      reduced in houses with Olyset nets compared with those with untreated nets or no
      nets. Thus, it may be concluded that Olyset nets are highly effective against
      malaria vectors and moderately against other nontarget household insects.

PMID- 17017225
TI  - Fumigant and repellent properties of essential oils and component compounds
      against permethrin-resistant Pediculus humanus capitis (Anoplura: Pediculidae)
      from Argentina.
AB  - The repeated use of permethrin and other insecticides for the control of head
      lice, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), during past
      decades has resulted in the development of marked levels of resistance. Thus, new
      alternative insecticides are needed for the control of head lice. We studied the
      fumigant and repellent properties of essential oils from 16 native and exotic
      plants in Argentina, and 21 chemical components against permethrin-resistant head
      lice from Argentina. With a direct vapor-exposure bioassay, the most effective
      oil was from the native Myrcianthes cisplatensis Cambess (Myrtaceae) with a time
      to 50% knockdown (KT50) of 1.3 min, followed by exotic species, Eucalyptus
      cinerea F.V. Muell., Eucalyptus viminalis Labill., and Eucalyptus saligna Smith.
      with KT50 values of 12.0, 14.9, and 17.4 min, respectively. The most effective
      components were 1,8-cineole and anisole, with KT50 values of 11.1 and 12.7 min,
      respectively. Regression analysis of KT50 values and vapor pressures and water
      partition coefficients for the essential oil components revealed that the most
      effective fumigants were among the more volatile components. Repellency assays
      indicated that the essential oil from Mentha pulegium L. and its benzyl alcohol
      component were the most effective repellents, having repellency indices of 75.5
      and 57.8%, respectively. Thus, some Argentinean plants contain essential oils and
      components that function as fumigants or as repellents and thereby show potential
      for development of new control products for head lice.

PMID- 17017226
TI  - Role of kdr and esterase-mediated metabolism in pyrethroid-resistant populations
      of Haematobia irritans irritans (Diptera: Muscidae) in Brazil.
AB  - The horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae), has become a
      problem for Brazilian cattle producers even though its introduction into Brazil
      is relatively recent. Failure to control this cattle pest is becoming a concern,
      and horn fly populations from several ranches from the state of Mato Grosso do
      Sul were surveyed for pyrethroid resistance. Susceptibility bioassays revealed
      that cypermethrin resistance was widespread and reached high levels in horn fly
      populations throughout the state, with resistance factors (RFs) ranging from 50.4
      to 704.8. Synergist bioassays failed to detect a major role for esterases as a
      pyrethroid resistance mechanism in these populations, except for the highly
      pyrethroid-resistant Estrela do Oeste population (RF = 704.8). The kdr sodium
      channel gene mutation was not detected in eight of the 13 populations, but < 7%
      of individuals from four populations and 50% of the flies from Estrela do Oeste
      exhibited this mutation. Neither the superkdr sodium channel gene mutation nor a
      resistance-associated gene mutation in the HialphaE7 carboxylesterase were found
      in any of the fly populations. Although target site insensitivity (kdr) and
      esterase-mediated metabolism occur in horn fly populations from Mato Grosso do
      Sul state, it seems that they are not the major mechanism causing pyrethroid
      resistance in most of these populations.

PMID- 17017227
TI  - Comparative trial of effectiveness of pyrethroid insecticides against
      peridomestic populations of Triatoma infestans in northwestern Argentina.
AB  - The effects of different pyrethroid insecticides, formulations, and doses on
      peridomestic populations of Triatoma infestans (Klug) were evaluated in 128
      houses with 148 identified infested peridomestic sites in northwestern Argentina
      between October 2003 and March 2005. Four treatments were randomly assigned
      within each community: two doses of 5% suspension concentrate beta-cypermethrin
      in water applied with manual compression sprayers, the standard dose (S) at 50 mg
      and a double dose (2S) at 100 mg active ingredient (AI)/m2; and two emulsifiable
      concentrates diluted in diesel fuel and applied with power sprayers, 25%
      cypermethrin (100 mg [AI] /m2) (CF) and 10% permethrin (170 mg [AI]/m2) (DF).
      Infestation was assessed by timed manual collections with a dislodging agent at
      baseline, 5, 12, and 17 mo postspraying, and the sites found to be reinfested at
      5 mo postspraying were selectively resprayed. Only 2S eliminated T. infestans
      from all peridomestic sites up to 12 mo postspraying, and it was significantly
      more effective than all other treatments. At 5 mo postspraying, more sites
      treated with CF or DF rather than S had bug colonies that probably represented
      residual foci, which they also failed in eliminating after a second spray. At 17
      mo postspraying, the prevalence of reinfested peridomestic sites was 5% for 2S,
      29% for S, 43% for CF, and 54% for DF. The application of suspension concentrate
      pyrethroids in dose twice as large as that currently in use in the attack phase
      produces a greater initial impact and may eliminate peridomestic populations of
      T. infestans.

PMID- 17017228
TI  - Sarcoptes scabiei (Acari: Sarcoptidae) mite extract modulates expression of
      cytokines and adhesion molecules by human dermal microvascular endothelial cells.
AB  - The inflammatory and immune responses seen with the worldwide disease scabies,
      caused by the mite Sarcoptes scabiei (De Geer) (Acari: Sarcoptidae), are complex.
      Clinical symptoms are delayed for weeks in patients when they are infested with
      scabies for the first time. This study was undertaken to elucidate the role of
      the human dermal microvascular endothelial cell (HMVEC-D) in modulating the
      inflammatory and immune responses in the skin to S. scabiei. Extracts of S.
      scabiei were incubated with HMVEC-D and the expression of adhesion molecules and
      chemokine receptors on the cells and the secretion of selected cytokines were
      determined by enzyme-linked immunosorbent assay. S. scabiei extract was found to
      inhibit HMVEC-D expression of E-selectin and vascular cell adhesion molecule-1,
      although not intercellular adhesion molecule-1. The secretion of interleukin-8
      also was inhibited by S. scabiei extract. S. scabiei extract increased expression
      of the chemokine receptor CXCR-1 and both down-regulated and up-regulated
      expression of CXCR-2, depending on the concentration tested. These findings help
      explain the delayed inflammatory reaction to infestation with S. scabiei.

PMID- 17017229
TI  - External surface disinfection of the lesser mealworm (Coleoptera: Tenebrionidae).
AB  - Understanding the dynamics of movement of bacteria within the environment and
      between species is crucial to unraveling the epidemiology of bacterial diseases
      and to developing biosecurity measures to prevent dissemination. Many arthropods,
      some beneficial and some detrimental, inhabit poultry houses. The lesser
      mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), is a pest
      commonly found in poultry litter that can harbor pathogens involved in both human
      and animal health issues. Current farm management practices perpetuate persistent
      infestations contributing to the dispersal of beetles and pathogens. To study the
      dissemination of bacteria by this beetle, we require the ability to differentiate
      internal from external sources of bacteria carried by the beetle. In this study,
      we tested previously described methods to externally disinfect beetles and found
      disinfectant efficacies between 40 and 98%. The irregular surface of the insect
      posed a challenge to cleansing procedures because the surface offered many
      recesses able to sequester bacteria. Complete bacterial disinfection was achieved
      with a serial treatment of ethanol and hydrogen peroxide or hydrogen
      peroxide/peracetic acid.

PMID- 17017230
TI  - Prevalence of Borrelia burgdorferi in small mammals in New York state.
AB  - Intensive small mammal trapping was conducted in 12 counties in New York state
      during 1998-2000 to investigate the prevalence and site specificity of the Lyme
      disease spirochete, Borrelia burgdorferi in, and presence of the blacklegged
      tick, Ixodes scapularis Say on, the wild mice Peromyscus leucopus Rafinesque and
      Peromyscus maniculatus Wagner and other small mammal species. Previously captured
      mice (1992-1997) from throughout New York state also were recruited into the
      study, providing a total of 3,664 Peromyscus from 107 sites in 31 counties.
      Infection with B. burgdorferi was determined by polymerase chain reaction testing
      of ear tissue, and rates were determined by species, counties, and regions of the
      state. B. burgdorferi was detected in 10 small mammal species captured during
      1998-2000. Peromyscus captured from Dutchess County in the lower Hudson Valley
      had the highest infection rate of 21%. The next highest infection rates were in
      counties within the Capital District: Albany (18%), Rensselaer (17%), and
      Columbia (13%). From 4,792 small animals examined, we recovered 2,073 ticks
      representing six species from 414 individuals of 12 mammal species, including
      1,839 I. scapularis collected from 315 Peromyscus trapped in five counties. I.
      scapularis were most often collected from animals trapped in Albany, Rensselear,
      and Dutchess counties. We used protein electrophoresis of salivary amylase to
      distinguish between P. leucopus and P. maniculatus species. I. scapularis burdens
      were 5.7 ticks per P. leucopus and 14.3 ticks per P. maniculatus.

PMID- 17017231
TI  - Horse-, bird-, and human-seeking behavior and seasonal abundance of mosquitoes in
      a West Nile virus focus of southern France.
AB  - After 35 yr of disease absence, West Nile virus (family Flaviviridae, genus
      Flavivirus, WNV) circulation has been regularly detected in the Camargue region
      (southern France) since 2000. WNV was isolated from Culex modestus Ficalbi, which
      was considered the main vector in southern France after horse outbreaks in the
      1960s. Recent WNV transmissions outside of the Cx. modestus distribution
      suggested the existence of other vectors. To study potential WNV vectors, horse-
      and bird-baited traps and human landing collections of mosquitoes were carried
      out weekly from May to October 2004 at two Camargue sites: one site in a wet area
      and the other site in a dry area, both chosen for their past history of WNV
      transmission. At the wet site, the most abundant species in bird-baited traps
      were Culex pipiens L. and Cx. modestus; both species also were found in lower
      proportions on horses and humans. The most abundant species in horse-baited traps
      and human landing collections were Aedes caspius (Pallas), Aedes vexans (Meigen),
      and Anopheles hyrcanus (Pallas) sensu lato; some of these species were
      occasionally collected with avian blood at the end of the summer. Anopheles
      maculipennis Meigen sensu lato was an abundant horse feeder, but it was rarely
      collected landing on human bait and never contained avian blood. At the dry site,
      Cx. pipiens was the most abundant species in bird- and horse-baited traps. The
      seasonal and circadian dynamics of these species are analyzed, and their
      potential in WNV transmission in Camargue discussed.

PMID- 17017232
TI  - Bloodmeal hosts of Anopheles species (Diptera: Culicidae) in a malaria-endemic
      area of the Brazilian Amazon.
AB  - Hosts of blood-fed anophelines (Diptera: Culicidae) were determined in three
      riverine villages, 1.5-7.0 km apart, along the Matapi River, Amapa state, Brazil,
      by enzyme-linked immunosorbent assay midgut analysis for IgG of common
      vertebrates. Anopheles marajoara Galvao & Damsceno and Anopheles darlingi Root
      had higher human blood indices (HBI) than Anopheles nuneztovari Gabaldon,
      Anopheles triannulatus (Neiva and Pinto), and Anopheles intermedius (Chagas),
      which were relatively zoophilic. HBIs of An. darlingi varied significantly among
      villages, attributable to a low proportion of human-fed mosquitoes in Santo
      Antonio. Significantly higher incidence of An. marajoara and An. nuneztovari fed
      on pig blood at two villages, associated with a low number of pigs in Santo
      Antonio. The incidences of bovine blood varied significantly among villages for
      all three of the most common anopheline species. The incidence of mixed meals
      ranged from 7.1 to 27.6% among common species, and, for An. marajoara, varied
      significantly among villages. This study demonstrates differences in host
      selection patterns among villages only a few kilometers apart, which may be
      influenced by host availability and have important epidemiological consequences.

PMID- 17017233
TI  - Repellent activity of fractioned compounds from Chamaecyparis nootkatensis
      essential oil against nymphal Ixodes scapularis (Acari: Ixodidae).
AB  - Preliminary repellent activity of 14 natural products isolated from essential oil
      components extracted from the heartwood of Alaska yellow cedar, Chamaecyparis
      nootkatensis (D. Don) Spach., were evaluated against nymphal Ixodes scapularis
      Say in a laboratory bioassay and compared with technical grade N,N-diethyl-3
      methylbenzamide (deet). Four hours after treatment, nootkatone and valencene-13
      ol had repellent concentration (RC)50 values of 0.0458 and 0.0712% (wt:vol),
      respectively; two additional Alaska yellow cedar compounds, nootkatone 1 --> 10
      epoxide and carvacrol had reported RC50 values of 0.0858 and 0.112%,
      respectively. The observed RC50 value for deet was 0.0728% (wt:vol). Although not
      statistically significantly more active than deet, the ability of these natural
      products to repel ticks at relatively low concentrations may represent a
      potential alternative to synthetic commercial repellents.

PMID- 17017234
TI  - Common house spiders are not likely vectors of community-acquired methicillin
      resistant Staphylococcus aureus infections.
AB  - There is an increasing incidence in the number of community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) infections in the United States. Skin and
      soft tissue infections caused by MRSA are often perceived as being preceded by a
      spider bite. Several possibilities exist to explain this phenomenon, including 1)
      spiders introduce MRSA into the bite wound and thereby serve as a potential
      vehicle or vector for MRSA; 2) MRSA colonization is an event secondary to the
      spider bite; and 3) the spider bite is a misguided way for patients or their
      physicians to explain the initial lesion of their skin or soft tissue infection.
      We hypothesized that if spiders were able to serve as vehicles or vectors for
      MRSA infections, they would be colonized with this pathogen. To test this
      hypothesis, we captured common household spiders and determined the patterns of
      normal microbial flora isolated from them. Spiders were collected from several
      homes by their occupants, photographed for identification, and cultured for
      external and internal microbial flora. Of > 100 spiders collected, none was found
      to carry Staphylococcus aureus or MRSA. Relatively low numbers of microbial flora
      were isolated, and only a single isolate with pathogenic potential in humans
      (Aeromonas spp.) was isolated. Common house spiders are unlikely to be a source
      of MRSA.

PMID- 17017235
TI  - The potential of Aedes triseriatus (Diptera: Culicidae) as an enzootic vector of
      West Nile virus.
AB  - The susceptibility of Aedes triseriatus (Say) (Diptera: Culicidae) to low levels
      of West Nile virus (family Flaviviridae, genus Flavivirus, WNV) was determined
      and compared with that of Culex pipiens L. to assess the likelihood of its
      participation in an enzootic cycle involving mammals. Ae. triseriatus and Cx.
      pipiens were exposed to WNV by feeding on baby chickens with WNV serum titers
      ranging from 10(4.1 +/- 0.1) to 10(8.6 +/- 0.1) plaque-forming units (PFU)/ml and
      from 10(4.1 +/- 0.1) to 10(7.0) PFU/ml, respectively. Infection rates and 95%
      confidence intervals (CIs) of 8% (4, 14) and 25% (15, 38) occurred in Ae.
      triseriatus and Cx. pipiens after feeding on chickens with WNV titers of 10(4.1
      +/- 0.1) PFU/ml and increased to 65% (49, 79) and 100% (72, 100) in Ae.
      triseriatus and Cx. pipiens after feeding on chickens with titers of 10(7.1 +/-
      0.1) PFU/ml. The mean infection rate of Ae. triseriatus ranged from 97% (84, 100)
      to 100% (79, 100) after feeding on chickens with WNV titers of > or = 10(8.2)
      PFU/ml. The infectious dose (ID)50 values for Ae. triseriatus and Cx. pipiens
      were 10(6.5) (6.4, 6.7) and 10(4.9) (4.6, 5.1) PFU/ml, respectively. The combined
      estimated transmission rate of Ae. triseriatus at 14 and 18 d after feeding on
      chickens with a mean WNV titer of 10(8.6 +/- 0.1) PFU/ml was 55%. Although Ae.
      triseriatus is significantly less susceptible to WNV than Cx. pipiens, the
      susceptibility of Ae. triseriatus to WNV titers < 10(5.0) PFU/ml and its ability
      to transmit WNV suggest that Ae. triseriatus has the potential to be an enzootic
      vector among mammalian populations.

PMID- 17017236
TI  - A Canadian bison isolate of Anaplasma marginale (Rickettsiales: Anaplasmataceae)
      is not transmissible by Dermacentor andersoni (Acari: Ixodidae), whereas ticks
      from two Canadian D. andersoni populations are competent vectors of a U.S.
      strain.
AB  - Anaplasma marginale Theiler is a tick-borne rickettsial pathogen of cattle with a
      global distribution in both temperate and tropical regions. The pathogen is
      endemic in regions within the United States, whereas the Canadian cattle
      population is considered to be free ofA. marginale. Farmed bison, Bison bison L.,
      in central Saskatchewan have been found to be infected with A. marginale;
      however, there is no evidence of transmission from bison to cattle. We tested a
      Saskatchewan bison isolate of A. marginale (SB1) to determine whether it is
      transmissible by the Rocky Mountain wood tick, Dermacentor andersoni Stiles.
      Colonized D. andersoni from the United States and Canada failed to transmit SB1.
      A separate transmission trial using D. andersoni adults reared from ticks
      collected in Alberta and British Columbia showed that ticks from these
      populations could successfully transmit the St. Maries, Idaho, strain of A.
      marginale. Although the Saskatchewan bison isolate of A. marginale seems not to
      be transmissible by D. andersoni, in the event of the introduction of a tick
      transmissible strain, Canadian D. andersoni are likely to be competent vectors.

PMID- 17017237
TI  - Spatial analysis of Aedes albopictus (Diptera: Culicidae) oviposition in suburban
      neighborhoods of a Piedmont community in North Carolina.
AB  - Temporal and spatial distribution of egg-laying by Aedes albopictus (Skuse)
      (Diptera: Culicidae) was investigated in suburban neighborhoods in Raleigh, NC,
      by using oviposition traps (ovitraps) at fixed sampling stations during the 2002
      and 2003 mosquito seasons. Variations in the phenology of oviposition between the
      two mosquito seasons resulted from differences in the patterns and amounts of
      rainfall early in the season. Aerial images of each study neighborhood were
      digitized, and the proportions of specific types of land cover within buffer
      zones encompassing ovitraps were estimated. Retrospective analyses showed that in
      some neighborhoods, oviposition intensity was significantly associated with
      specific types of land cover. However, in general, it seemed that gravid Ae.
      albopictus searched throughout the landscape for water-filled containers in which
      to lay eggs. Peridomestic surveys were carried out concurrently with ovitrap
      collections to estimate production of Ae. albopictus pupae in discarded water
      filled containers and the abundance of females in vegetation that made up the
      resting habitat. Results of linear regression analyses indicated that the mean
      standing crop of pupae (total and per container) per residence was not a
      significant predictor of mean egg densities in ovitraps. However, the mean
      standing crop of adult females was a significant but weak predictor variable,
      because the magnitude and sign of regression coefficients varied between
      neighborhoods. Linear spatial regression analyses revealed that oviposition
      intensity was not spatially dependent on pupal standing crop or the numbers of
      pupae-positive containers distributed peridomestically. However, a weak spatial
      dependence on the standing crop of adult females was found in some neighborhoods.
      Based on spherical variogram models, kriging was carried out to predict the
      spatial patterns of oviposition in suburban neighborhoods. Focal areas of high
      and low oviposition intensity were evident in most neighborhoods; however, the
      spatial patterns of oviposition changed between mosquito seasons. Kriging
      predictions were evaluated, using cross-validation, by systematically removing
      each data point from our data set and predicting the removed point by using the
      remaining points. The root mean square (standardized) error values of best
      fitting variogram models approximated 1, and plots of standardized PRESS
      residuals showed no distinct pattern for most neighborhoods, indicating that
      predictions of the spatial distribution of oviposition intensity were valid.
      Spherical variogram models are a satisfactory method for describing the spatial
      distribution of Ae. albopictus oviposition, and kriging can be a useful technique
      for predicting oviposition intensity at locations that have not been sampled.

PMID- 17017238
TI  - Effect of abiotic factors on seasonal population dynamics of Lutzomyia
      longipalpis (Diptera: Psychodidae) in northeastern Brazil.
AB  - The resurgence of visceral leishmaniasis in Brazil increases the need for studies
      to elucidate the spatial and temporal dynamics of Lutzomyia longipalpis (Lutz and
      Neiva) (Diptera: Psychodidae), the vector of Leishmania infantum, the causative
      agent of visceral leishmaniasis in Brazil. Sand flies were captured in
      peridomestic habitats biweekly for 3 yr. Cross-correlation tests and spectral
      analysis were used to analyze the simultaneous and lag-time correlations between
      Lu. longipalpis population densities and abiotic factors of temperature, relative
      humidity, wind velocity, and rainfall. Distinct seasonal patterns were observed
      for males and females, with intervals of 6 mo between population peaks for males
      and 12 mo for females. Peak female population densities lagged 3 mo behind the
      maximum annual temperature. Female population density was negatively correlated
      with relative humidity. An increase in average wind velocity was followed by a
      decrease in the number of females for 2 wk. Understanding the relationship
      between the seasonal population dynamics of Lu. longipalpis and abiotic factors
      will contribute to the design of better control measures to decrease transmission
      of L. infantum and consequently the incidence of leishmaniasis.

PMID- 17017239
TI  - Importance of waste stabilization ponds and wastewater irrigation in the
      generation of vector mosquitoes in Pakistan.
AB  - The objective of the current study was to investigate the role of waste
      stabilization ponds (WSP) and wastewater-irrigated sites for the production of
      mosquitoes of medical importance. Mosquito larvae were collected fortnightly from
      July 2001 to June 2002 in Faisalabad, Pakistan. In total, 3,132 water samples
      from WSP and irrigated areas yielded 606,053 Culex larvae of five species. In
      addition, 107,113 anophelines, representing eight species were collected.
      Anopheles subpictus (Grassi) and Culex mosquitoes, especially Culex
      quinquefasciatus (Say) and Culex tritaeniorhynchus (Giles), showed an
      overwhelming preference for anaerobic ponds, which receive untreated wastewater.
      Facultative ponds generated lower numbers of both Anopheles and Culex mosquitoes,
      whereas the last ponds in the series, the maturation ponds, were the least
      productive for both mosquito genera. An. subpictus and Anopheles stephensi
      (Liston) were the dominant Anopheles species in wastewater-irrigated sites, with
      Anopheles culicifacies (Giles) recorded in low numbers. This was also the pattern
      in nearby sites, irrigated with river water. Among the Culex species, Cx.
      tritaeniorhynchus was by far the most frequently recorded in both wastewater- and
      river water-irrigated sites with Cx. quinquefasciatus as the second most abundant
      species but restricted to wastewater-irrigated areas. Univariate logistic
      regression analysis showed that presence of An. subpictus and Culex mosquitoes
      was significantly associated with emergent grass vegetation and low salinity.
      Regular removal of emergent grass along the margins of the anaerobic ponds and
      changes in the concrete design of the ponds are likely to reduce the mosquito
      production, especially of Culex species.

PMID- 17017240
TI  - Isolation of Bunyamwera serogroup viruses (Bunyaviridae, Orthobunyavirus) in New
      York state.
AB  - During routine arbovirus surveillance from 2000 to 2004 in New York state (NYS),
      14,788 mosquito pools making up 36 species and nine genera were inoculated onto
      Vero cell cultures to test for abroad spectrum of viruses. Forty-six percent of
      viruses isolated in cell culture from species, excluding Culex pipiens L. and
      Culex restuans Theobald, were identified as Bunyamwera serogroup viruses. Here,
      we report the distribution and level of Bunyamwera activity in NYS detected
      during this period. We developed specific primers for Cache Valley virus (family
      Bunyaviridae, genus Orthobunyavirus, CVV) and Potosi virus (family Bunyaviridae,
      genus Orthobunyavirus, POTV), to facilitate rapid molecular identification of
      these viruses. Viral RNA was detected in 12 mosquito species by reverse
      transcription-polymerase chain reaction, with the majority isolated from Aedes
      trivittatus (Coquillet). We report the first POTV isolation in NYS and describe
      the development of specific primers to identify both POTV and CVV.

PMID- 17017241
TI  - West Nile virus from female and male mosquitoes (Diptera: Culicidae) in
      subterranean, ground, and canopy habitats in Connecticut.
AB  - In total, 93,532 female mosquitoes (Diptera: Culicidae) were captured in traps
      placed in subterranean (catch basin), ground (approximately 1.5 m above ground),
      and canopy (approximately 7.0 m above ground) habitats in Stamford and Stratford,
      CT, during 2003-2005. Culex pipiens L. was the most abundant (64.8%) of the 31
      species identified. Significantly greater numbers of Cx. pipiens were captured in
      canopy-placed mosquito magnet experimental traps, and significantly greater
      numbers were collected in catch basin-placed (Centers for Disease Control) CDC
      traps than in CDC traps placed elsewhere. Culex restuans Theobald was captured in
      significantly greater numbers in traps placed in catch basins. Aedes vexans
      (Meigen), Aedes cinereus Meigen, and Aedes cantator (Coquillett) were
      significantly more abundant in ground traps. In total, 429 isolations of West
      Nile virus (WNV) were made from seven species of mosquitoes from late June
      through the end of October during 2003 through 2005. Three hundred ninety-eight
      (92.8%) isolates were from Cx. pipiens. Others were from Cx. restuans (n = 16),
      Culex salinarius Coquillett (n = 5), Ae. vexans (n = 4), Ae. cantator (n = 3),
      Aedes triseriatus (Say) (n = 2), and Ae. cinereus (n = 1). Multiple isolates from
      Cx. pipiens were made each week, primarily during the later part of July through
      the end of September. Weekly minimum infection rates (MIRs) were lower in 2004
      (highest weekly MIR = 7.1) when no human cases were reported in Connecticut in
      comparison with 2003 and 2005 (highest weekly MIR = 83.9) when human cases were
      documented. Frequencies of infected pools were significantly higher in Cx.
      pipiens captured in traps in the canopy and significantly higher in catch basin
      placed traps than in traps at ground level. The physiological age structure of
      Cx. pipiens captured in the canopy was significantly different from that of Cx.
      pipiens collected in catch basins. Invariably, Cx. pipiens captured in the canopy
      were nulliparous or parous with ovaries in Christophers' stage 2, whereas 58.7%
      of the females captured in catch basins possessed ovaries filled with mature
      oocytes in Christophers' stage 5. Our results suggest that females in the canopy
      are seeking hosts, and after digestion of the bloodmeal and development of mature
      oocytes, they descend to catch basins for shelter and deposition of eggs. WNV was
      isolated from three, one, and two pools of male Cx. pipiens captured in catch
      basin-, ground-, and canopy-placed traps, respectively, and from six nulliparous
      Cx. pipiens females collected in the canopy. Weekly MIR ranged from 1.2 to 31.1
      per 1,000 male specimens. These data show that mosquitoes become infected by
      means other than by blood feeding, possibly by transovarial transmission. The
      placement of traps in tree canopies and in catch basins can be used to augment
      current practices of placement of traps near the ground for surveillance of
      mosquitoes infected with WNV and for studies of the ecology of WNV.

PMID- 17017242
TI  - Detection of West Nile virus RNA in pools of three species of ceratopogonids
      (Diptera: Ceratopogonidae) collected in Louisiana.
AB  - Light traps were used to collect ceratopogonids in East Baton Rouge parish,
      Louisiana. In total, 46,496 ceratopogonids were sorted from 4,968 light trap
      collections from 20 November 2002 through 25 November 2004. Two hundred and nine
      pools containing specimens of 18 species of Culicoides Latreille, seven pools
      containing specimens of Atrichopogon Kieffer, and five pools containing specimens
      of Forcipomyia Meigen were tested for West Nile virus (family Flaviviridae, genus
      Flavivirus, WNV) RNA using real-time reverse transcriptase polymerase chain
      reaction. Five out of the 209 pools of Culicoides specimens were positive for WNV
      RNA.

PMID- 17017243
TI  - Components of developmental plasticity in a Michigan population of Lucilia
      sericata (Diptera: Calliphoridae).
AB  - Forensic entomologists rely on laboratory growth data to estimate the time of
      blow fly colonization on human remains. Several data sets exist for the
      development of the common blow fly Lucilia sericata (Meigen) (Diptera:
      Calliphoridae), and although they generally describe similar rates of preadult
      development, all vary. Such differences could be explained by genetic variation,
      environmental (rearing) variation, or both. In the study presented here, flies
      from a single population were reared under variable conditions of food moisture,
      substrate type, substrate freshness, and sampling, to determine the effect each
      had on developmental time. Cohorts were tested in a single incubator at a single
      temperature and humidity, to eliminate effects of undesired environmental
      variation. Fly developmental times were significantly influenced by multiple
      laboratory rearing treatments; food moisture, transferring postfeeding larvae to
      fresh substrate, and destructive sampling affected different stages of
      development. Developmental times ranged from 329 to 505.5 h, covering the
      spectrum of variation observed in published data sets. Growth was then compared
      with larval development on rat carcasses under the same environmental conditions,
      establishing a link between laboratory-controlled growth and development on
      carrion. Cohorts raised on rats matured to adulthood between 333 and 337 h, which
      was best mimicked by the fastest growth treatment observed under laboratory
      conditions. The large environmental influence on development observed in this
      study could affect forensic entomology casework and accentuates the need for a
      standardized means of rearing flies in a laboratory setting that is relevant to
      decomposition on a corpse.

PMID- 17017244
TI  - Mosquito larval habitat mapping using remote sensing and GIS: implications of
      coalbed methane development and West Nile virus.
AB  - Potential larval habitats of the mosquito Culex tarsalis (Coquillett), implicated
      as a primary vector of West Nile virus in Wyoming, were identified using
      integrated remote sensing and geographic information system (GIS) analyses. The
      study area is in the Powder River Basin of north central Wyoming, an area that
      has been undergoing a significant increase in coalbed methane gas extractions
      since the late 1990s. Large volumes of water are discharged, impounded, and
      released during the extraction of methane gas, creating aquatic habitats that
      have the potential to support immature mosquito development. Landsat TM and ETM+
      data were initially classified into spectrally distinct water and vegetation
      classes, which were in turn used to identify suitable larval habitat sites. This
      initial habitat classification was refined using knowledge-based GIS techniques
      requiring spatial data layers for topography, streams, and soils to reduce the
      potential for overestimation of habitat. Accuracy assessment was carried out
      using field data and high-resolution aerial photography commensurate with one of
      the Landsat images. The classifier can identify likely habitat for ponds larger
      than 0.8 ha (2 acres) with generally satisfactory results (72.1%) with a lower
      detection limit of approximately 0.4 ha (1 acre). Results show a 75% increase in
      potential larval habitats from 1999 to 2004 in the study area, primarily because
      of the large increase in small coalbed methane water discharge ponds. These
      results may facilitate mosquito abatement programs in the Powder River Basin with
      the potential for application throughout the state and region.

PMID- 17017245
TI  - Ross River virus disease clusters and spatial relationship with mosquito biting
      exposure in Redland Shire, southern Queensland, Australia.
AB  - The spatial heterogeneity in the risk of Ross River virus (family Togaviridae,
      genus Alphavirus, RRV) disease, the most common mosquito-borne disease in
      Australia, was examined in Redland Shire in southern Queensland, Australia.
      Disease cases, complaints from residents of intense mosquito biting exposure, and
      human population data were mapped using a geographic information system. Surface
      maps of RRV disease age-sex standardized morbidity ratios and mosquito biting
      complaint morbidity ratios were created. To determine whether there was
      significant spatial variation in disease and complaint patterns, a spatial scan
      analysis method was used to test whether the number of cases and complaints was
      distributed according to underlying population at risk. Several noncontiguous
      areas in proximity to productive saline water habitats of Aedes vigilax (Skuse),
      a recognized vector of RRV, had higher than expected numbers of RRV disease cases
      and complaints. Disease rates in human populations in areas which had high
      numbers of adult Ae. vigilax in carbon dioxide- and octenol-baited light traps
      were up to 2.9 times those in areas that rarely had high numbers of mosquitoes.
      It was estimated that targeted control of adult Ae. vigilax in these high-risk
      areas could potentially reduce the RRV disease incidence by an average of 13.6%.
      Spatial correlation was found between RRV disease risk and complaints from
      residents of mosquito biting. Based on historical patterns of RRV transmission
      throughout Redland Shire and estimated future human population growth in areas
      with higher than average RRV disease incidence, it was estimated that RRV
      incidence rates will increase by 8% between 2001 and 2021. The use of arbitrary
      administrative areas that ranged in size from 4.6 to 318.3 km2 has the potential
      to mask any small scale heterogeneity in disease patterns. With the availability
      of georeferenced data sets and high-resolution imagery, it is becoming more
      feasible to undertake spatial analyses at relatively small scales.

PMID- 17017246
TI  - Infestation of rural houses by Triatoma infestans (Hemiptera: Reduviidae) in
      southern area of Gran Chaco in Argentina.
AB  - The impact of control activities against Triatoma infestans (Klug) (Hemiptera:
      Reduviidae) in South America has a marked contrast within and outside the Gran
      Chaco region. Development of a geographic information system, as part of an
      improvement in control program activities, allowed analysis of the spatial
      pattern of house infestations by T. infestans before and after house spraying
      with deltamethrin in the San Martin Department (an arid Chaco region of central
      Argentina). The overall peridomestic infestation index decreased from 48.2 to
      28.2% after insecticide application. House infestation was spatially clustered in
      regions with low or high infestation levels that were located east and southwest
      of the department, respectively. This pattern was detected both before and after
      the insecticide application. Three environmental variables calculated from a
      temporal series of MODIS imagery (average of night temperature, maximum of day
      temperature, and temporal variation of vegetation index) were capable of
      correctly discriminating 96% of the places belonging to either high or low house
      infestation observed after the insecticide application.

PMID- 17017247
TI  - Environmental factors associated with distribution and range limits of malaria
      vector Anopheles farauti in Australia.
AB  - Ecological factors associated with the narrow coastal distribution of Anopheles
      farauti Laveran s.s. were investigated using decision tree software and a
      recently developed software tool that permits analysis of environmental gradients
      across distributional boundaries. Significant variables identified by these
      procedures were then used to develop ecological niche models that permitted
      detailed--and improved--predictions of the species' overall distribution. These
      methods identified seven climatic factors (four of temperature factors and three
      atmospheric moisture factors) from among 40 environmental variables related to
      the range of this species. In addition, the gradient-analysis tool identified
      elevation as being particularly important. The distributional hypothesis
      predicted using ecological niche modeling of these factors included all of the
      record sites from which An. farauti s.s. was collected in northern Australia and
      successfully reconstructed its narrow limitation to coastal areas. Omission of
      elevation from analyses resulted in unrealistic predictions of potential
      distributional areas > 100 km inland, where the species has not been found.

PMID- 17017248
TI  - Laboratory transmission of Japanese encephalitis, West Nile, and Getah viruses by
      mosquitoes (Diptera: Culicidae) collected near Camp Greaves, Gyeonggi Province,
      Republic of Korea 2003.
AB  - We conducted experimental studies to evaluate mosquitoes captured in Paju County,
      Gyeonggi Province, Republic of Korea, for their ability to transmit West Nile
      virus (family Flaviviridae, genus Flavivirus, WNV), Japanese encephalitis virus
      (family Flaviviridae, genus Flavivirus, JEV), and Getah virus (family
      Togaviridae, genus Alphavirus, GETV) under laboratory conditions. Both Culex
      pipiens pallens Coquillett and Culex tritaeniorhynchus Giles were highly
      susceptible to infection with WNV, with infection rates > 65% when allowed to
      feed on chickens with viremias of approximately 10(7) plaque-forming units (PFU)
      of virus/ml blood. In contrast, Cx. tritaeniorhynchus were significantly more
      susceptible to JEV or GETV (infection rate 100%) than were the Cx. p. pallens
      (infection rate 3% for JEV and 0% for GETV) captured in the same area when
      allowed to feed on chickens with viremias of approximately 10(5) PFU of virus/ml
      blood. The detection of JEV in field-collected Cx. tritaeniorhynchus in Gyeonggi
      Province in 2000 and the demonstrated ability of this species to transmit this
      virus support the importance of the continued vaccination of Koreans against JEV
      and indicate a risk of infection for nonvaccinated individuals.

PMID- 17017249
TI  - Malaria transmission and insecticide resistance of Anopheles gambiae (Diptera:
      Culicidae) in the French military camp of Port-Bouet, Abidjan (Cote d'Ivoire):
      implications for vector control.
AB  - An important vector control program is ongoing to lower the risk of malaria
      transmission in the French military camp of Port-Bouet, Abidjan (Cote d'Ivoire).
      However, some autochthonous malaria cases are regularly suspected. An
      entomological survey was conducted in June 2004 in the camp to assess malaria
      transmission and evaluate the pyrethroid and organophosphate resistance of the
      malaria vectors. The average mosquito biting rate was 178.0 bites per person per
      night. Mosquitoes belonging to the Anopheles gambiae (Diptera: Culicidae) complex
      and the Anopheles funestus group were collected. An. gambiae s.s. molecular form
      M was the only species of the An. gambiae complex present. The average number of
      An. gambiae bites was approximately 44.3 per person per night. The
      circumsporozoite index was 0.38% and the entomological inoculation rate estimated
      to be 1.2 infective bites per week for the study period. The kdr and ace1 gene
      frequencies in the An. gambiae population were 0.70 and 0.15, respectively.
      Personnel living in the French barracks of Port-Bouet are thus at high risk of
      being bitten by parasite-infected mosquitoes. Such an entomological inoculation
      rate, usually found in African peri-urban environments, was unexpected
      considering the extensive effort deployed to control mosquitoes in the camp.
      Insecticide resistance could explain the inefficacy of the vector control program
      but the spraying strategy is also questionable.

PMID- 17017250
TI  - Identification of avian- and mammalian-derived bloodmeals in Aedes vexans and
      Culiseta melanura (Diptera: Culicidae) and its implication for West Nile virus
      transmission in Connecticut, U.S.A.
AB  - To evaluate the host-feeding patterns of Aedes vexans (Meigen) and Culiseta
      melanura (Coquillett) as secondary vectors of West Nile virus (family
      Flaviviridae, genus Flavivirus, WNV) in Northeastern United States, we identified
      the source of vertebrate bloodmeals by sequencing portions of the cytochrome b
      gene of mitochondrial DNA. Analysis of polymerase chain reaction products from a
      total of 119 Ae. vexans revealed that 92.4% of individuals acquired blood solely
      from mammalian and 2.5% from avian hosts. Mixed bloodmeals from both avian and
      mammalian hosts were detected in 5% of individuals of this species. Ae. vexans
      obtained vertebrate bloodmeals most frequently from white-tailed deer (80%)
      followed by domestic horse, American robin, eastern cottontail, and domestic cat.
      In contrast, Cs. melanura fed predominantly on avian species (89.6%) but
      exhibited some inclination for mammalian blood (4.2%). Individual mosquitoes
      containing mixed bloodmeals were also identified in 6% of Cs. melanura. American
      robin was the most common source of vertebrate blood for Cs. melanura (23%),
      followed by wood thrush and gray catbird. American crow represented only 2% of
      the bloodmeals identified in Cs. melanura, as was similarly found with other
      recognized Culex vectors of WNV in the northeast. These findings support the view
      that Ae. vexans is likely to be a relatively important "bridge vector" to large
      mammals, including deer and horse, whereas Cs. melanura likely plays a secondary
      role in enzootic transmission of WNV among free-ranging birds in more rural
      environs.

PMID- 17017251
TI  - Emergence of the introduced ant Pachycondyla chinensis (Formicidae: Ponerinae) as
      a public health threat in the southeastern United States.
AB  - Pachycondyla chinensis (Emery) (Formicidae: Ponerinae), a species introduced into
      North America > 70 yr ago, is found throughout Southeast Asia. Stinging of
      zookeepers by P. chinensis at the Greenville Zoo (Greenville, SC) initiated an
      investigation of this exotic species and a survey of sting victims. Eighty
      percent of sting victims experienced local reactions, including swelling < 5 cm
      in diameter around the sting site, recurring pain, skin redness, and mild-to
      severe urticaria. These symptoms lasted 2 h to 5 d. Twelve percent of the sting
      victims reported minor reactions, including no swelling, localized redness, minor
      pain sensation at the time of sting, mild urticaria, and symptoms lasting < 1 h.
      Eight percent of the sting victims reported significant local reactions,
      including swelling > 5 cm in diameter around the sting site, recurring pain, skin
      redness, severe urticaria, and symptoms lasting 3-14 d. P. chinensis represents
      an emerging public health threat throughout its present range in the southeastern
      United States (i.e., Georgia, North Carolina, South Carolina, and Virginia).
      Because of reported adverse reactions to stings of P. chinensis, further studies
      on its ecology and medical and veterinary importance need to be undertaken.

PMID- 17017252
TI  - A spotted fever group Rickettsia from an exotic tick species, Amblyomma exornatum
      (Acari: Ixodidae), in a reptile breeding facility in the United States.
AB  - Adults and nymphs of Amblyomma exornatum Koch (Acari: Ixodidae), an exotic
      African tick of monitor lizards, were collected from a Gray's monitor lizard,
      Varanus olivaceus Hallowell, that died in a reptile facility in Alabama. Nine
      adult ticks were tested by polymerase chain reaction for rickettsial agents. DNA
      from a novel spotted fever group Rickettsia was amplified and sequenced from one
      of the nine ticks. The novel Rickettsia was most similar to "Rickettsia anan,"
      which is associated with Amblyomma from Asia. The detection of a spotted fever
      group Rickettsia in exotic ticks emphasizes the potential threat posed by the
      importation and propagation of exotic animals in the United States.

PMID- 17017253
TI  - Why American business demands twenty-first century skills: an industry
      perspective.
AB  - Public education is the key to individual and business prosperity. With a vested
      stake in education, educators, employers, parents, policymakers, and the public
      should question how this nation's public education system is faring. Knowing that
      recent international assessments have shown little or no gains in American
      students' achievement, the author asserts the clear need for change. As both a
      large American corporate employer and a provider of technology for schools, Dell
      is concerned with ensuring that youth will thrive in their adult lives. Changing
      workplace expectations lead to a new list of skills students will need to acquire
      before completing their schooling. Through technology, Dell supports schools in
      meeting educational goals, striving to supply students with the necessary skills,
      referred to as twenty-first century skills. The Partnership for 21st Century
      Skills, of which Dell is a member, has led an initiative to define what twenty
      first century learning should entail. Through extensive research, the partnership
      has built a framework outlining twenty-first century skills: analytical thinking,
      communication, collaboration, global awareness, and technological and economic
      literacy. Dell and the partnership are working state by state to promote the
      integration of these skills into curricula, professional development for
      teachers, and classroom environments. The authors describe two current
      initiatives, one in Virginia, the other in Texas, which both use technology to
      help student learning. All stakeholders can take part in preparing young people
      to compete in the global economy. Educators and administrators, legislators,
      parents, and employers must play their role in helping students be ready for what
      the workforce and the world has in store for them.

PMID- 17017254
TI  - Why American business demands twenty-first century learning: A company
      perspective.
AB  - Microsoft is an innovative corporation demonstrating the kind and caliber of job
      skills needed in the twenty-first century. It demonstrates its commitment to
      twenty-first century skills by holding its employees accountable to a set of core
      competencies, enabling the company to run effectively. The author explores how
      Microsoft's core competencies parallel the Partnership for 21st Century Skills
      learning frameworks. Both require advanced problem-solving skills and a passion
      for technology, both expect individuals to be able to work in teams, both look
      for a love of learning, and both call for the self-confidence to honestly self
      evaluate. Microsoft also works to cultivate twenty-first century skills among
      future workers, investing in education to help prepare young people for
      competitive futures. As the need for digital literacy has become imperative,
      technology companies have taken the lead in facilitating technology training by
      partnering with schools and communities. Microsoft is playing a direct role in
      preparing students for what lies ahead in their careers. To further twenty-first
      century skills, or core competencies, among the nation's youth, Microsoft has
      established Partners in Learning, a program that helps education organizations
      build partnerships that leverage technology to improve teaching and learning. One
      Partners in Learning grantee is Global Kids, a nonprofit organization that trains
      students to design online games focused on global social issues resonating with
      civic and global competencies. As Microsoft believes the challenges of competing
      in today's economy and teaching today's students are substantial but not
      insurmountable, such partnerships and investments demonstrate Microsoft's belief
      in and commitment to twenty-first century skills.

PMID- 17017255
TI  - Why the American public supports twenty-first century learning.
AB  - Aware that constituent support is essential to any educational endeavor, the AOL
      Time Warner Foundation (now the Time Warner Foundation), in conjunction with two
      respected national research firms, measured Americans' attitudes toward the
      implementation of twenty-first century skills. The foundation's national research
      survey was intended to explore public perceptions of the need for changes in the
      educational system, in school and after school, with respect to the teaching of
      twenty-first century skills. The author summarizes the findings of the survey,
      which were released by the foundation in June 2003. One thousand adults were
      surveyed by telephone, including African Americans, Latinos, teachers, and
      business executives. In general, the survey found that Americans believe today's
      students need a "basics-plus" education, meaning communication, technology, and
      critical thinking skills in addition to the traditional basics of reading,
      writing, and math. In fact, 92 percent of respondents stated that students today
      need different skills from those of ten to twenty years ago. Also, after-school
      programs were found to be an appropriate vehicle to teach these skills.
      Furthermore, the survey explored how well the public perceives schools to be
      preparing youth for the workforce and postsecondary education, which twenty-first
      century skills are seen as being taught effectively, and the level of need for
      after-school and summer programs. The survey results provide conclusive evidence
      of national support for basics-plus education. Thus, a clear opportunity exists
      to build momentum for a new model of education for the twenty-first century.

PMID- 17017256
TI  - Why America's disadvantaged communities need twenty-first century learning.
AB  - Current school reform efforts, emphasizing data and accountability, have shed
      additional light on racial and income-based inequities in education. To tackle
      this achievement gap, the discrepancies in the nation's educational system must
      be examined within the context of the increasing economic demand for higher skill
      levels. The author asserts that the education system is not educating all
      students to the levels necessary to fulfill America's quest for international
      excellence. Demonstrating the inadequacies of the current educational system,
      this chapter draws from Murnane and Levy's research emphasizing a need for new
      basic skills. The author cites Murnane and Levy's finding that up to half of all
      graduates leave high school without the skills necessary to compete in today's
      economy. Students are not getting enough out of school to succeed in the
      workforce. These data prompt the author's support for out-of-school-time
      programs. An opportunity gap exists when it comes to how children from various
      socioeconomic backgrounds spend their out-of-school time. Children from
      disadvantaged families experience much less enrichment, further contributing to
      the achievement gap. Quality after-school programs-not just "more school"-can
      fill this void, providing the enrichment and academic support needed to gain the
      skills required to succeed in the modern workforce. The Nellie Mae Education
      Foundation's Critical Hours: Afterschool Programs and Educational Success
      confirms the need for out-of-school-time programs by showing the relationship
      between an effective after-school program and academic success. Ultimately the
      after-school movement will reduce educational inequality, allowing today's youth
      to contribute to America's international competitiveness.

PMID- 17017257
TI  - Why the changing American economy calls for twenty-first century learning:
      answers to educators' questions.
AB  - While struggling with the current pressures of educational reform, some educators
      will ask whether their efforts make economic sense. Questioning the future makeup
      of the nation's workforce, many wonder how the educational system should be
      tempered to better prepare today's youth. This chapter answers educators' and
      parents' questions around the effect of fluctuations in the American economy on
      the future of education. The authors offer reassurance that good jobs will always
      be available, but warn that those jobs will require a new level of skills: expert
      thinking and complex communication. Schools need to go beyond their current
      curriculum and prepare students to use reading, math, and communication skills to
      build a deeper and more thoughtful understanding of subject matter. To explain
      the implications of the nation's changing economy on jobs, technology, and
      therefore education, the authors address a range of vital questions. Citing
      occupational distribution data, the chapter explores the supply and range of jobs
      in the future, as well as why changes in the U.S. job distribution have taken
      place. As much of the explanation for the shift in job distribution over the past
      several decades is due to the computerization of the workforce, the authors
      discuss how computers will affect the future composition of the workforce. The
      chapter also addresses the consequences of educational improvement on earnings
      distribution. The authors conclude that beyond workforce preparedness, students
      need to learn how to be contributing members of a democracy.

PMID- 17017258
TI  - Establishing the R&D agenda for twenty-first century learning.
AB  - An infusion of twenty-first century skills into American public education
      necessitates a plan for research and development to further such reform. While
      the nation agrees that students must obtain critical thinking, problem-solving,
      and communication skills to succeed in the current global marketplace, this
      chapter puts forth a long-term, proactive agenda to invest in targeted research
      to propel and sustain this shift in education. The authors examine the impact
      such an R&D agenda would have on pedagogy and assessment and the implications for
      institutions of higher education. As the United States struggles to maintain
      dominance in the international economy, it faces a great challenge in keeping up
      with European and Asian competitors' strategies for preparing youth for the
      global marketplace. The authors hope the global reality will help contextualize
      the debate around American education--the current trend toward basics and
      accountability needs to be broadened. Building on frameworks created by the
      Partnership for 21st Century Skills, this chapter proposes questions to guide
      research around teaching, professional development, and assessment significant to
      twenty-first century skills. Knowing that educational change depends on providing
      teachers with the tools, support, and training to make fundamental changes in
      their practice, the authors argue for extensive research around best practices.
      In addition, if assessments are created to measure the desired outcomes, such
      measuring tools can drive reform. Furthermore, large-scale changes in teacher
      preparation programs must take place to allow teachers to adequately employ
      twenty-first century teaching and assessment strategies.

PMID- 17017259
TI  - Twenty-first century learning in afterschool.
AB  - Twenty-first century skills increasingly represent the ticket to the middle
      class. Yet, the authors argue, in-school learning is simply not enough to help
      students develop these skills. The authors make the case that after-school (or
      out-of-school) learning programs are emerging as one of the nation's most
      promising strategies for preparing young people for the workforce and civic life.
      Most school systems have significant limitations for teaching twenty-first
      century skills. They have the limits of time: with only six hours per day there
      is barely enough time to teach even the basic skills, especially for those
      students starting already behind. They have the limits of structure: typical
      school buildings and classrooms are not physically set up for innovative
      learning. They have the limits of inertia and bureaucracy: school systems are
      notoriously resistant to change. And perhaps most important, they have the limits
      of priorities: especially with the onset of the No Child Left Behind Act, schools
      are laserlike in their focus on teaching the basics and therefore have less
      incentive to incorporate twenty-first century skills. Meanwhile, the authors
      argue that after-school programs are an untapped resource with three competitive
      advantages. First, they enable students to work collaboratively in small groups,
      a setup on which the modern economy will increasingly rely. Second, they are well
      suited to project-based learning and the development of mastery. Third, they
      allow students to learn in the real-world contexts that make sense. Yet the after
      school sector is fraught with challenges. It lacks focus-Is it child care, public
      safety, homework tutoring? And it lacks rigorous results. The authors argue that
      the teaching of twenty-first century skills should become the new organizing
      principle for afterschool that will propel the field forward and more effectively
      bridge in-school and out-of-school learning.

PMID- 17017260
TI  - Twenty-first century learning in schools: A case study of New Technology High
      School in Napa, California.
AB  - The most pertinent question concerning teaching and learning in the twenty-first
      century is not what knowledge and skills students need--that laundry list was
      identified over a decade ago--but rather how to foster twenty-first century
      learning. What curricula, experiences, assessments, environments, and technology
      best support twenty-first century learning? New Technology High School (NTHS) in
      Napa, California, is one example of a successful twenty-first century school. In
      this chapter, the author describes the components of this exemplary high school,
      illustrating an environment that will cultivate twenty-first century student
      learning. New Technology High School began by defining eight learning outcomes,
      aligned with the standards of the Partnership for 21st Century Skills; to
      graduate, students demonstrate mastery of these outcomes through an online
      portfolio. To help students achieve the outcomes, NTHS employs project- and
      problem-based learning. Whereas in traditional classrooms students work alone on
      short-term assignments that do not lend themselves to deep understanding, the
      project-based learning approach has students working in teams on long-term, in
      depth, rigorous projects. Students' work is supported by the school's workplace
      like environment and effectiv use of technology. Meaningful assessment is
      essential to project-based learning; students receive continuous feedback,
      helping them become self-directed learners. In fact, NTHS uses outcome-based
      grading through which students constantly know how they are performing on the
      twenty-first century outcomes. Research has shown that NTHS graduates are better
      prepared for postsecondary education, careers, and citizenship than their peers
      from other schools. To facilitate twenty-first century learning, all schools need
      to rethink their approach to teaching and learning. New Technology High School is
      one way to do so.

PMID- 17017261
TI  - Twenty-first century learning in school systems: the case of the Metropolitan
      School District of Lawrence Township, Indianapolis, Indiana.
AB  - To empower students with skills such as information and technological literacy,
      global awareness and cultural competence, self-direction, and sound reasoning,
      teachers must master these skills themselves. This chapter examines how the
      Digital Age Literacy Initiative of the Metropolitan School District of Lawrence
      Township in Indianapolis, Indiana, which is funded by the Lilly Endowment,
      incorporated twenty-first century learning through a systemic approach involving
      teacher training and the use of data. The authors explain the district's content,
      process, and context goals toward accomplishing its mission of empowering
      students with the necessary twenty-first century skills to succeed in the digital
      age. The district places a strong emphasis on professional development for
      teachers. To support the necessary teacher learning and therefore sustain the
      work of the initiative, the district has adopted action research, self
      assessment, and an online professional development network. To support teachers
      in implementing new strategies, master teachers serve as digital age literacy
      coaches. The chapter discusses the initiative's focus on evidence of progress.
      Through a partnership with the Metiri Group of California, the district has built
      a range of assessments including online inventories and twenty-first century
      skill rubrics. For example, the Mankato Survey collected teacher and student data
      around access, ability, and use of technology in the classroom in 2001 and then
      in 2004. This research showed significant gains in some technologies across all
      grade levels and consistent gains in nearly all technologies for middle and high
      school students. As it moves into the next phase of implementing the Digital Age
      Literacy Initiative, the district embraces the systemic shifts in school culture
      necessary to institutionalize twenty-first century learning.

PMID- 17017262
TI  - Twenty-first century learning in states: the case of the Massachusetts
      educational system.
AB  - A current crisis in education is leaving students less prepared to succeed in the
      working world than any generation before them. Increasingly complex external,
      nonacademic pressures have an impact on many of today's students, often causing
      them to drop out of school. Only 76 percent of Massachusetts high school students
      graduate, and only 29 percent earn a college degree. National figures are worse.
      Most educational institutions share a common goal to support students in becoming
      skilled, productive, successful members of society, but the author argues that
      this goal is not being met. Despite the constant changes in the world,
      educational practices have remained static. Most public schools are not adapting
      to meet the shifting needs of students. Universities are not able to prepare the
      right mix of prospective employees for the demands of the job market; for
      example, schools are graduating only 10 percent of the needed engineers.
      Institutions of higher learning cannot keep up with employers' needs in an
      evolving global market: strong math, science, and writing abilities; critical
      thinking skills; and the ability to work in teams. The author draws on exemplary
      efforts at work in his home state of Massachusetts--whose improvements in student
      achievement outcomes have been some of the best in the nation--to suggest there
      is promise in twenty-first century learning. Middle school students involved in a
      NASA-funded project write proposals, work in teams, and engage in peer review.
      Older students participate in enhanced, hands-on cooperative school-to-work and
      after-school programs. Schools are starting to offer expanded day learning,
      increasing the number of hours they are engaged in formal learning. Yet such
      programs have not reached significant levels of scale. The author calls for a
      major shift in education to help today's students be successful in the twenty
      first century.

PMID- 17017263
TI  - Twenty-first century learning after school: the case of 4-H.
AB  - Founded in the early 1900s, the 4-H Youth Development program can serve as a
      model for out-of-school programs of the twenty-first century. The 4-H pledge,
      repeated by its members--over 7 million, ranging in age from five to twenty-
      articulates its core values: "I pledge: My head to clearer thinking, My heart to
      greater loyalty, My hands to larger service, and My health to better living for
      my club, my community, my country, and my world." The 4-H Development movement
      was created to provide opportunities for rural children, to help them become
      constructive adults. Through an emphasis on "learning by doing," 4-H teaches
      children the habits of lifelong learning. Historically, 4-H has tapped into
      university-level advancements, extending such knowledge to youth and thereby
      giving them early access to scientific discoveries and technological progress.
      Members apply this learning in their communities through hands-on projects
      crossing a wide-range of pertinent topics. Research shows that 4-H members are
      more successful in school than other children and develop a wide range of skills
      essential in the twenty-first century. Thus, the author makes the case that the
      foundation of 4-H is exceptionally relevant in today's complex world, perhaps
      even more so than a century ago. 4-H is a leader in youth development, making it
      a natural model for twenty-first century after-school programs. Expanding on the
      4-H pledge, the author outlines the principles a successful youth development
      program would have: an emphasis on leadership skills, a feeling of connection and
      belonging, a forum for exploring career opportunities, and a component of
      meaningful community service.

PMID- 17017264
TI  - Twenty-first century learning after school: the case of Junior Achievement
      Worldwide.
AB  - Efforts to increase after-school programming indicate the nation's concern about
      how youth are engaged during out-of-school time. There are clear benefits to
      extending the learning that goes on during the school day. Research from the U.S.
      Departments of Education and Justice shows that after-school participants do
      better in school and have stronger expectations for the future than youth who are
      not occupied after school. And the need is evident: 14.3 million students return
      to an empty house after school, yet only 6.5 million children are currently
      enrolled in after-school programs. If an after-school program were available,
      parents of 15.3 million would enroll their child. JA Worldwide began in 1919 and
      has been rooted in the afterschool arena from its origins. Its after-school
      programs teach students about the free enterprise system through curriculum
      focusing on business, citizenship, economics, entrepreneurship, ethics and
      character, financial literacy, and career development. At the same time, JA
      Worldwide incorporates hands-on learning and engagement with adults as role
      models, both key elements to a successful after-school program. Now focused on
      developing curriculum emphasizing skills needed for the twenty-first century, JA
      adopted the key elements laid out for after-school programs by the Partnership
      for 21st Century Skills. To ensure that the next generation of students enters
      the workforce prepared, America's education system must provide the required
      knowledge, skills, and attitudes. Programs such as JA Worldwide serve as models
      of how to provide the twenty-first century skills that all students need to
      succeed.

PMID- 17017265
TI  - Twenty-first century learning for teachers: helping educators bring new skills
      into the classroom.
AB  - The motivation behind every educator's dedication and hard work in the classroom
      is the knowledge that his or her teaching will result in students' success in
      life. Educators are committed to implementing twenty-first century skills; they
      have no question that students need such skills to be equipped for life beyond
      school. Members of the National Education Association are enthusiastic about the
      Partnership for 21st Century Skills framework, yet express frustration that many
      schools do not have adequate resources to make the necessary changes. Teaching
      these skills poses significant new responsibilities for schools and educators. To
      make it possible for teachers to build twenty-first century skills into the
      curriculum, physical and policy infrastructures must exist, professional
      development and curriculum materials must be offered, and meaningful assessments
      must be available. With an established understanding of what skills need to be
      infused into the classroom-problem solving, analysis, and com- munications-and
      educators' commitment to the new skill set, this chapter explores how to make
      such a dramatic reform happen. The author discusses existing strategies that will
      guide educators in infusing twenty-first century skills into traditional content
      areas such as math, English, geography, and science. Ultimately, public policy
      regarding educational standards, professional development, assessments, and
      physical school structures must exist to enable educators to employ twenty-first
      century skills, leading to student success in contemporary life. Any concern
      about the cost of bringing this nation's educational system up to par
      internationally should be offset by the price that not making twenty-first
      century skills a priority in the classroom will have on future economic well
      being.

PMID- 17017266
TI  - Twenty-first century skills for students: hands-on learning after school builds
      school and life success.
AB  - At the core of the movement for twenty-first century skills are students. The
      growing efforts to increase programs leveraging out-of-school time are focused on
      giving American youth everything they need to compete in this increasingly
      complex world. The author is one of many students who have been well served by
      initiatives imparting twenty-first century skills during after-school hours. Now
      a senior at Boston Latin School, the author has been helped along the way by
      Citizen Schools, an after-school education program focused on hands-on learning
      apprenticeships and homework help. While enrolled in the program as a middle
      school student, the author took part in projects that exemplified hands-on,
      inquiry-based learning that helped her develop twenty-first century skills. For
      example, along with dozens of other students, she advanced her data analysis
      skills by analyzing statistics about Boston Public high schools, which also
      helped her select and enroll in one of the city's premier exam schools. Also, she
      and her peers worked with corporate attorneys who served as writing coaches and
      whose expertise the author drew from in producing a published essay and greatly
      improving her writing skills. The author now finds that the public speaking,
      leadership, organizational, social, and management abilities she built through
      her participation in Citizen Schools are a great asset to her in high school. The
      confidence with which she tackles her responsibilities can also be traced back to
      her experiences in the program. As she looks toward college, the author reflects
      and realizes that being actively involved in a quality after-school program put
      her on track for a successful future.

PMID- 17017267
TI  - Direct access physical therapy and diagnostic responsibility: the risk-to-benefit
      ratio.

PMID- 17017268
TI  - Comparison of foot kinematics between subjects with posterior tibialis tendon
      dysfunction and healthy controls.
AB  - STUDY DESIGN: A 2 x 4 mixed-design ANOVA with a fixed factor of group (posterior
      tibialis tendon dysfunction [PTTD] and asymptomatic controls), and a repeated
      factor of phase of stance (loading response, midstance, terminal stance, and
      preswing). OBJECTIVE: To compare 3-dimensional stance period kinematics (rearfoot
      eversion/inversion, medial longitudinal arch [MLA] angle, and forefoot abduction)
      of subjects with stage II PTTD to asymptomatic controls. BACKGROUND: Abnormal
      foot postures in subjects with stage II PTTD are clinical indicators of disease
      progression, yet dynamic investigations of forefoot, midfoot, and rearfoot
      kinematic deviations in this population are lacking. METHODS: Fourteen subjects
      with stage II PTTD were compared to 10 control subjects with normal arch index
      values. Subjects were matched for age, gender, and body mass index. A 5-segment,
      kinematic model of the leg and foot was tracked using an Optotrak Motion Analysis
      System. The dependent kinematic variables were rearfoot inversion/eversion,
      forefoot abduction/adduction, and the MLA angle. An ANOVA model was used to
      compare kinematic variables between groups across 4 phases of stance. RESULTS:
      Subjects with PTTD demonstrated significantly greater rearfoot eversion (P =
      .042), MLA angle (P = .008) and forefoot abduction angles (P < .005) during
      specific phases of stance. Subjects with PTTD demonstrated significantly greater
      rearfoot eversion (P<.004) and MLA angles (P < .009) by 6.2 degrees and 8.0
      degrees, respectively, during loading response when compared to controls. During
      preswing, the subjects with PTTD demonstrated a significantly greater MLA angle
      (P < .002) and a forefoot abduction angle (P<.001) which exceeded that of the
      controls by 10.0 degrees. CONCLUSIONS: The abnormal kinematics observed at the
      rearfoot, midfoot, and forefoot across all phases of stance implicate a failure
      of compensatory muscle and secondary ligamentous support to control foot
      kinematics in subjects with stage II PTTD.

PMID- 17017269
TI  - Concurrent criterion-related validity and reliability of a clinical device used
      to assess lateral patellar displacement.
AB  - STUDY DESIGN: Repeated-measures, within-subject design. OBJECTIVE: To assess the
      concurrent criterion-related validity and reliability of a clinical device to
      quantify lateral patellar displacement. BACKGROUND: Excessive lateral
      displacement of the patella is an impairment that is widely associated with
      patellofemoral pain and/or pathology. Currently, no valid or reliable clinical
      method to assess lateral patellar displacement has been described in the
      literature. METHODS AND MEASURES: A total of 26 individuals (14 asymptomatic and
      12 symptomatic; mean +/- SD age, 27 +/- 4 years) participated in the validity
      portion of this study, while an additional 10 asymptomatic volunteers (mean +/-
      SD age, 28 +/- 5 years) participated in the reliability portion. Lateral
      displacement of the patella was assessed using a custom-designed patellofemoral
      arthrometer (PFA) and was compared to actual position of the patella as
      determined by magnetic resonance imaging (MRI). Both PFA and MRI measurements of
      lateral patellar displacement were made with the knee extended and the quadriceps
      contracted. The intraclass correlation coefficient (ICC) was used to assess the
      level of agreement between the PFA and MRI measurements, as well as the
      intrarater and interrater reliability of the PFA measurements. RESULTS: The ICC
      assessing the level of agreement between the MRI and PFA measures of lateral
      patellar displacement was good (0.86). Excellent intratester (ICC, 0.96 and 0.97)
      and intertester reliability (ICC, 0.92) were demonstrated. CONCLUSION: Our
      results suggest that reasonable estimations of lateral patellar displacement can
      be obtained using the PFA.

PMID- 17017270
TI  - The intertester reliability of the Scapular Assistance Test.
AB  - STUDY DESIGN: Test-retest reliability study. OBJECTIVE: To determine interrater
      reliability of the modified scapular assistance test (SAT). The modified SAT is
      designed to assess the contribution of scapular motion to shoulder pain.
      BACKGROUND: Abnormal scapular motion has been implicated in different shoulder
      disorders. However, there is a lack of clinical evaluation tools to assess the
      scapular component of shoulder dysfunction. METHODS AND MEASURES: Forty-six
      subjects who were referred to physical therapy for treatment of various shoulder
      pathologies were recruited for this study. The modified SAT was performed on each
      participant by 2 different examiners. Percent agreement and kappa coefficient
      were utilized to determine interrater reliability of the modified SAT. RESULTS:
      The kappa coefficient and percent agreement were .53 and 77%, respectively, when
      the test was performed in the scapular plane, and .62 and 91%, respectively, when
      the test was performed in the sagittal plane. CONCLUSIONS: The modified SAT
      possesses acceptable interrater reliability for clinical use.

PMID- 17017271
TI  - The role of fibular tape in the prevention of ankle injury in basketball: A pilot
      study.
AB  - STUDY DESIGN: Prospective nonrandomized controlled trial. OBJECTIVES: To
      determine the effect of fibular repositioning tape (FRT) on incidence and
      severity of ankle injury. BACKGROUND: Pain and functional disability is common
      following ankle sprain and a major problem in sport. A novel method of taping,
      FRT, which has been described to prevent ankle sprain, requires less tape than
      traditional methods and is easier to apply. The objective of this study was to
      determine the effect of FRT on the incidence and severity of ankle injury in
      basketball. METHODS AND MEASURES: One hundred twenty-five male basketball players
      were assigned at time of play to either the control (209 exposures) or FRT (224
      exposures) condition in a manner of convenience. Control participants had the
      choice on the use and type of prophylaxis, excluding FRT. FRT participants were
      taped using the method described by Mulligan. Ankle injury data were collected
      after each exposure. Injury severity was determined by functional limitation,
      pain levels, and days to return to play. RESULTS: Four hundred forty-three
      measured basketball exposures resulted in 11 ankle injuries. All injuries
      occurred in subjects with a history of previous ankle sprain. Significantly less
      ankle injuries were sustained by members of the FRT condition (n = 2), compared
      to members of the control condition (n = 9) (Fisher exact test, P = .03). The
      odds ratio of sustaining an ankle injury was 0.20 (P = .04; 95% confidence
      interval [CI]: 0.04, 0.93) when taped with FRT and the number needed to treat was
      22 (95% CI, 12-312). CONCLUSIONS: This study provides preliminary data regarding
      the prophylactic effects of FRT on ankle injury in male basketball players.

PMID- 17017272
TI  - Use of pulsed shortwave diathermy and joint mobilization to increase ankle range
      of motion in the presence of surgical implanted metal: A case series.
AB  - STUDY DESIGN: Case series. BACKGROUND: Traditionally, all forms of diathermy have
      been contraindicated over metal implants. There is a lack of research-based
      evidence for harm regarding the use of pulsed shortwave diathermy (PSWD) over
      orthopedic metal implants. Because PSWD is an effective modality for deep
      heating, we investigated whether ankle range of motion (ROM) could improve with
      the cautious use of PSWD and joint mobilizations, despite orthopedic metal
      implants being in the treatment field. CASE DESCRIPTIONS: Four subjects presented
      with decreased ankle ROM due to extensive fractures from traumatic injuries. All
      subjects were postsurgical, with several internal fixation devices. Subjects
      previously received rehabilitation therapy involving joint mobilizations,
      therapeutic exercises, moist heat, and ice, but continued to lack 15 degrees to
      23 degrees of ankle dorsiflexion. The Human Subjects Review Board of Brigham
      Young University approved the methods of this case series. Subjects gave written
      informed consent. Initial dorsiflexion active ROM for each patient was -3
      degrees, 0 degrees, 8 degrees, and 5 degrees, respectively. Treatment regime
      consisted of PSWD to the ankle for 20 minutes at 27.12 MHz, 800 pps, 400
      microseconds (48 W). Immediately after PSWD, mobilizations were administered to
      the joints of the ankle and foot. Ice was applied posttreatment. OUTCOMES:
      Dorsiflexion improved 15 degrees, 15 degrees, 10 degrees, and 14 degrees,
      respectively, after 8 or 13 visits. All patients returned to normal activities
      with functional ROM in all planes. Follow-up 4 to 6 weeks later indicated that
      the subjects maintained 78% to 100% of their dorsiflexion. No discomfort, pain,
      or burning was reported during or after treatment. No negative effects were
      reported during the short-term follow-up. DISCUSSION: When applied with
      appropriate caution, we propose PSWD (48 W) may be an appropriate adjunct to
      joint mobilizations to increase ROM in peripheral joints, despite implanted
      metal. We continue to advise caution when applying diathermy with machines other
      than the Megapulse II. Further research is needed to determine the safety
      parameters of other diathermy machines. As a final caution, we advise that
      diathermy not be used in the presence of a cardiac pacemaker or neurostimulator.

PMID- 17017273
TI  - The use of neuromuscular electrical stimulation to improve activation deficits in
      a patient with chronic quadriceps strength impairments following total knee
      arthroplasty.
AB  - STUDY DESIGN: Case report. BACKGROUND: Long-term deficits in quadriceps femoris
      muscle strength and impaired muscle activation are common among individuals with
      total knee arthroplasty (TKA). Failure to address strength-related impairments
      results in poor surgical and functional outcomes, which may accelerate the
      progression of osteoarthritis in other lower extremity joints. The purpose of the
      current case report was to implement a neuromuscular electrical stimulation
      (NMES) treatment protocol in conjunction with an intense weight-training program,
      with the aim of reversing persistent quadriceps muscle impairments after TKA.
      CASE DESCRIPTION: The patient was a 62-year-old male cyclist 12 months following
      simultaneous, bilateral TKA with impairments in left quadriceps strength and
      volitional muscle activation. His left quadriceps strength was 26% weaker than
      his right and central activation ratio (CAR) of his left quadriceps was 13% lower
      than his right quadriceps CAR. NMES to the left quadriceps was implemented for 6
      weeks, in addition to an intense volitional weight-training program with emphasis
      on unilateral lower extremity exercises. OUTCOMES: The patient demonstrated a 25%
      improvement in left quadriceps femoris maximal volitional force output following
      16 treatments of combined NMES and volitional strength training over a 6-week
      period. The patient's volitional muscle activation improved from a CAR of 0.83
      before treatment to 0.97 after treatment. At discharge from physical therapy and
      at his 18-month postoperative follow-up, the patient's left quadriceps strength
      was only 4% lower than his right quadriceps strength. At the 24-month follow-up,
      the patient's left quadriceps strength was 6% stronger than his right quadriceps
      strength. DISCUSSION: The patient was able to achieve symmetrical quadriceps
      strength and complete muscle activation following 6 weeks of NMES and volitional
      strength training. An intense strengthening program may have the potential to
      reverse persistent strength-related impairments following TKA.

PMID- 17017274
TI  - Deep vein thrombosis in an athletic military cadet.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: A 21-year-old healthy athletic
      male military cadet with complaint of worsening diffuse left knee pain was
      evaluated 4 days after onset. The knee pain began 2 hours after completing a long
      car trip, worsened over the subsequent 3 days, and became almost unbearable
      during the return trip. The patient reported constant pain, limited knee motion,
      and difficulty ambulating. In addition, he was unable to perform physical
      military training or attend academic classes due to the severe left knee pain.
      Past medical history revealed a mild left lateral calf strain 21/2 weeks prior,
      which completely resolved within 24 hours of onset. DIAGNOSIS: Our physical
      examination led us to either monoarticular arthritis, pseudothrombophlebitis
      (ruptured Baker's cyst), or a lower leg deep vein thrombosis (DVT) as the cause
      of knee pain. Diagnostic imaging of this patient revealed a left superficial
      femoral vein thrombosis and popliteal DVT, with bilateral pulmonary emboli (PE).
      DISCUSSION: A systematic differential diagnosis was undertaken to rule out a
      potentially fatal DVT diagnosis as the cause of knee pain, despite minimal DVT
      risk factors. The physical therapist in a direct-access setting must ensure
      timely evaluation and referral of a suspected DVT, even when patient demographics
      cause the practitioner to question the likelihood of this diagnosis. The physical
      examination findings, clinical suspicion, and established clinical prediction
      rules can accurately dictate the appropriate referral action necessary.

PMID- 17017275
TI  - Individual differences in the influence of phonological characteristics on
      expressive vocabulary development by young children.
AB  - The current study attempts to differentiate effects of phonotactic probability
      (i.e. the likelihood of occurrence of a sound sequence), neighbourhood density
      (i.e. the number of phonologically similar words), word frequency, and word
      length on expressive vocabulary development by young children. Naturalistic
      conversational samples for three children (age 1;4-3; 1) were obtained from
      CHILDES. In a backward regression analysis, phonotactic probability,
      neighbourhood density, word frequency, and word length were entered as possible
      predictors of ages of first production of words for each child. Results showed
      that the factors affecting first production of words varied across children and
      across word types. Specifically, word length affected ages of first production
      for all three children, whereas the other three variables affected only one child
      each. The implications of these findings for models of expressive vocabulary
      development are discussed.

PMID- 17017276
TI  - Priming overgeneralizations in two- and four-year-old children.
AB  - Overgeneralization occurs when a child uses the wrong word to name an object and
      is often observed in the early stages of word learning. We develop a method to
      elicit overgeneralizations in the laboratory by priming children to say the names
      of objects perceptually similar to known and unknown target objects. Experiment 1
      examined 18 two-year-old children's labelling of familiar and unfamiliar objects,
      using a name that was previously produced. Experiment 2 compared the labelling of
      30 two-year-olds and 39 four-year-olds when presented with completely novel
      objects. The findings suggest that the retrieved word is a blend of previous
      activation from the prior retrieval and activation engendered by the similarity
      of the test object to instances of the target category. We put forward a
      theoretical account of overgeneralization based on current models of adult
      language processing. The account suggests a common mechanism of activation and
      retrieval, which may explain not only momentary lapses in the correct selection
      of words, but other types of naming errors traditionally thought to reflect
      differences in children's underlying category representations or, perhaps, gaps
      in their knowledge of words.

PMID- 17017277
TI  - Facilitation and practice in verb acquisition.
AB  - This paper presents a model of syntax acquisition, whose main points are as
      follows: Syntax is acquired in an item-based manner; early learning facilitates
      subsequent learning--as evidenced by the accelerating rate of new verbs entering
      a given structure; and mastery of syntactic knowledge is typically achieved
      through practice--as evidenced by intensive use and common word order errors--and
      this slows down learning during the early stages of acquiring a structure. The
      facilitation and practice hypotheses were tested on naturalistic production
      samples of six Hebrew-acquiring children ranging from ages 1;1 to 2;7 (average
      ages 1;6 to 2;4 months). Results show that most structures did in fact
      accelerate; the notion of 'practice' is supported by the inverse correlation
      found between number of verbs and number of errors in the earliest productions in
      a given structure; and the absence of acceleration in a minority of the
      structures is due to the fact that they involve relatively less practice.

PMID- 17017278
TI  - Comparing different accounts of inversion errors in children's non-subject wh
      questions: 'What experimental data can tell us?'.
AB  - This study investigated different accounts of children's acquisition of non
      subject wh-questions. Questions using each of 4 wh-words (what, who, how and
      why), and 3 auxiliaries (BE, DO and CAN) in 3sg and 3pl form were elicited from
      28 children aged 3;6-4;6. Rates of noninversion error (Who she is hitting?) were
      found not to differ by wh-word, auxiliary or number alone, but by lexical
      auxiliary subtype and by wh-word+lexical auxiliary combination. This finding
      counts against simple rule-based accounts of question acquisition that include no
      role for the lexical subtype of the auxiliary, and suggests that children may
      initially acquire wh-word + lexical auxiliary combinations from the input. For DO
      questions, auxiliary-doubling errors (What does she does like?) were also
      observed, although previous research has found that such errors are virtually non
      existent for positive questions. Possible reasons for this discrepancy are
      discussed.

PMID- 17017279
TI  - Polish children's productivity with case marking: the role of regularity, type
      frequency, and phonological diversity.
AB  - 57 Polish-speaking children aged from 2;4, to 4;8 and 16 adult controls
      participated in a nonce-word inflection experiment testing their ability to use
      the genitive, dative and accusative inflections productively. Results show that
      this ability develops early: the majority of two-year-olds were already
      productive with all inflections apart from dative neuter; and the overall
      performance of the four-year-olds was very similar to that of adults. All age
      groups were more productive with inflections that apply to large and/or
      phonologically diverse classes, although class size and token frequency appeared
      to be more important for younger children (two- and three-year-olds) and
      phonological diversity for older children and adults. Regularity, on the other
      hand, was a very poor predictor of productivity. The results support usage-based
      models of language acquisition and are problematic for the dual mechanism model.

PMID- 17017280
TI  - I'm sorry I said that: apologies in young children's discourse.
AB  - We examined children's use of apology terms in parent-child discourse.
      Longitudinal data from 9 children (5 males, 4 females) between the ages of 1;2
      and 6;1 were analysed. Before 2;0, the use of apology terms was rare. Thereafter,
      several developmental trends were noted including a decrease with age in directly
      elicited apologies and an increase in indirectly elicited apologies. With age
      children's apologies also became more elaborate. Children were exposed to apology
      terms primarily through apologies directed to them and, to a lesser degree, in
      talk about apologies. Our study documents young children's early mastery of an
      important pragmatic skill and identifies parents' role in its acquisition.

PMID- 17017281
TI  - Typological effects on spelling development: a crosslinguistic study of Hebrew
      and Dutch.
AB  - This study investigates the role of phonological and morphological information in
      children's developing orthographies in two languages with different linguistic
      typologies: Hebrew, a Semitic language with a highly synthetic morphology, and
      Dutch, a Germanic language with a sparse morphology. 192 Israeli and 192 Belgian
      monolingual schoolchildren in grades 1-6 (aged 6;0-12;0) were administered
      respective dictation tasks in which homophonous segments were the targets. In
      each language, these phonologically distinct segments are neutralized
      phonetically but are nevertheless represented orthographically. In both languages
      the target segments in the test words differed along two dimensions: (1) their
      morphological function as part of a stem or root versus as part of an affix; and
      (2) their morphophonological recoverability. The spelling tests in both languages
      consisted of four conditions which differed in the number and type of cues for
      retrieving the correct spelling of homophonous graphemes. The cues were of two
      types: morphological cues, which offer spellers clues to the correct spelling
      through consistent orthography/morphology mapping regularities; and
      morphophonological cues, which offer spellers clues to the correct spelling
      through the manipulation of orthography/morphophonology conversion procedures. A
      central finding of this study is the differential treatment of morphological cues
      by Dutch and Hebrew spelling learners. When faced with neutralized segments with
      and without morphological function, Hebrew-speaking children find morphology an
      enormously helpful tool. Dutch-speaking children, in contrast, do not find
      morphology a good cue provider. The impact of typology on the interface between
      spoken and written language is invoked as an explanation of the main findings.

PMID- 17017282
TI  - Effects of familiarity on mothers' talk about nouns and verbs.
AB  - Modifications mothers make when talking to young English-speaking children
      between the ages of 1;8 and 3;0 (average age = 2;4) about words perceived to be
      familiar versus unfamiliar were investigated. Nineteen mothers and their children
      participated in two toy play tasks; one designed to elicit talk about familiar
      and unfamiliar animals and the other designed to elicit talk about familiar and
      unfamiliar actions. It was found that mothers' talk involving unfamiliar words
      differed from talk involving familiar words in a number of ways. Some
      modifications served to highlight the unfamiliar word which could assist in
      segmenting the unfamiliar word and mapping it to its referent. Compared to
      familiar nouns and verbs, unfamiliar nouns and verbs were produced more
      frequently in highly salient utterance positions and were paired more
      consistently with a clear nonverbal referent. Familiar nouns but, not verbs, were
      produced in longer utterances than unfamiliar nouns which could support the
      child's elaboration of the lexical representation of the familiar word.

PMID- 17017283
TI  - When answer-phone makes a difference in children's acquisition of English
      compounds.
AB  - Over the course of acquiring deverbal compounds like truck driver, English
      speaking children pass through a stage when they produce ungrammatical compounds
      like drive-truck. These errors have been attributed to canonical phrasal ordering
      (Clark, Hecht & Mulford, 1986). In this study, we compared British and Canadian
      children's compound production. Both dialects have the same phrasal ordering but
      some different lexical items (e.g. answer-phone exists only in British English).
      If influenced by these lexical differences, British children would produce more
      ungrammatical Verb-Object (VO) compounds in trying to produce the more complex
      deverbal (Object-Verb-er) than the Canadian children. 36 British children between
      the ages of 3;6 and 5;6 and 36 age-matched Canadian children were asked to
      produce novel compounds (like sun juggler). The British children produced more
      ungrammatical compounds and fewer grammatical compounds than the Canadian
      children. We argue that children's errors in deverbal compounds may be due in
      part to competing lexical structures.

PMID- 17017284
TI  - Physical activity and health promotion.

PMID- 17017285
TI  - Promoting physical activity globally for population health.

PMID- 17017286
TI  - Physical activity measurement--a primer for health promotion.
AB  - As the importance of physical activity is recognised in health promotion, the
      task of measuring it becomes a central research and practice challenge.
      Measurement of physical activity is important to policy makers interested in
      population surveillance, as well as to practitioners interested in programme
      evaluation and research. This review outlines 'best practice' in physical
      activity measurement, and provides an inventory of established physical activity
      and related measures for use in health promotion programme evaluation, research
      and surveillance at the national and local level.

PMID- 17017287
TI  - An evidence-based approach to physical activity promotion and policy development
      in Europe: contrasting case studies.
AB  - Evidence-based public health takes many of the principles of evidence-based
      medicine and applies them to public health. This is a relatively young discipline
      however and is not universally applied to public health issues--especially such
      multidisciplinary topics as physical activity. This paper sets out to provide
      guidance on this issue by characterising four 'key tasks' that form the basis of
      a systematic evidence-based approach to promoting physical activity. These tasks
      are based in part on the physical activity promotion model (Brownson et
      al.,1999). These are illustrated with examples from work in three contrasting
      European countries: Finland, England and Switzerland. 'Task one' is concerned
      with using the evidence for the health benefits of physical activity to 'make the
      case' and increase action by policy makers. Here, all three countries took a
      similar approach, conducting academic reviews to draw together the existing
      evidence of the health benefits of physical activity. 'Task two' is concerned
      with conducting surveillance to collect evidence on the prevalence of physical
      activity. Here, Finland and Switzerland were careful to collect trend data and
      use them for advocacy, while in England continuous changes to questionnaires and
      survey methodologies have led to poor trend data. 'Task three' is to review
      evidence on 'what works' in increasing physical activity to influence practice.
      England appears to be taking a more systematic approach to this task, with a
      comprehensive approach to reviewing evidence on what works and disseminating this
      to influence good practice, while the other countries rely mainly on individual
      evaluation studies. 'Task four' is the evaluation of practice and it is clear
      that in all three countries this remains a significant challenge--one requiring
      additional training and dedicated funding. As a result much of current "good
      practice" is based upon experience (usually unevaluated) and not evidence. This
      brief analysis shows that there are some common tasks that need to be undertaken
      as a central part of an evidence-based public health approach. However, cultural
      and political factors in each country studied have influenced the manner in which
      these tasks were undertaken, and the importance attached to each component.

PMID- 17017288
TI  - A framework for evaluating community-based physical activity promotion programmes
      in Latin America.
AB  - A growing interest in promoting physical activity through multi-sectoral
      community-based programmes has highlighted the need for effective programme
      evaluation. Meeting in Rio de Janeiro, an international workgroup of behavioural,
      medical, public health and other scientists and practitioners endorsed the
      principle of careful evaluation of all programmes and in a consensus process
      developed the Rio de Janeiro Recommendations for Evaluation of Physical Activity
      Interventions". Among these recommendations and principles were that when
      possible, evaluation should 'built into' the programme from the beginning. The
      workgroup also called for adequate funding for evaluation, setting a goal of
      about 10% of programme resources for evaluation. The group also determined that
      evaluations should be developed in conjunction with and the results shared with
      all appropriate stakeholders in the programme; evaluations should be guided by
      ethical standards such as those proposed by the American Evaluation Association
      and should assess programme processes as well as outcomes; evaluation outcomes
      should be used to revise and refine ongoing programmes and guide decisions about
      programme continuation or expansion. It was also recognised that additional
      training in programme evaluation is needed and the Centers for Disease Control
      and Prevention's Physical Activity Evaluation Handbook could be easily adapted
      for use in culturally diverse communities, especially in Latin America. This
      paper describes a 6-step evaluation process and provides the full set of
      recommendations from the Rio de Janeiro Workgroup. The handbook has been
      translated and additional case studies from Colombia and Brazil have been added.
      Spanish and Portuguese language editions of the Evaluation Handbook are available
      from the Centers for Disease Control and Prevention, Physical Activity and Health
      Branch.

PMID- 17017289
TI  - Advocacy for physical activity--from evidence to influence.
AB  - Advocacy is an evolving and underdeveloped element of public health practice.
      Historically, it was used to describe activities undertaken by persons on behalf
      of the poor, the sick or oppressed. In the seventies, led by tobacco control
      advocates such as Pertschuk in the United States, Gray in Australia and Daube in
      the United Kingdom, public health advocacy became more focused on structural and
      policy change. Since the Ottawa Charter (WHO, 1986), the health promotion
      movement has embraced a broader view of the role of advocacy. The public health
      community now see advocacy as social action primarily aimed at effecting changes
      in legislation, policy and environments that support healthy living. Advocacy is
      defined by the World Health Organization as a combination of individual and
      social actions designed to gain political commitment, policy support, social
      acceptance and systems support for a particular health goal or programme (WHO,
      1995). This paper describes a model for understanding and mobilising physical
      activity advocacy. It outlines a three step process: 1. Gathering and translating
      the most pertinent physical activity evidence. Why advocate for physical
      activity? 2. Developing from the evidence, a physical activity advocacy agenda
      and articulating a plan (or plans) of key actions that will increase population
      levels of physical activity. What should be advocated? 3. Implementing a mix of
      advocacy strategies to influence and mobilise support for the physical activity
      agenda. How should advocacy be implemented?

PMID- 17017290
TI  - Implementing national population-based action on physical activity--challenges
      for action and opportunities for international collaboration.
AB  - This paper summarises recent past and current international developments on
      physical activity looking at the challenges and opportunities they pose. Key
      elements of the WHO's Global Strategy on Diet, Physical Activity and Health
      (GSDPAH) are summarised, focusing specifically on the physical activity
      components, and by drawing upon recent fora (Atlanta, October 2002; Miami,
      December 2004; Cascais, February 2005; Beijing, October 2005; Bogota, November
      2005), we outline the barriers and areas of support required for successful
      development and implementation of national, population-based action on physical
      activity. These gatherings focused particularly on the needs of developing
      countries, where to date little has been done to augment physical activity at a
      population level. Unless swift action is taken, these countries will soon suffer
      significantly from an increased prevalence of non communicable diseases (NCD).
      Existing initiatives and opportunities for national and international action on
      physical activity are identified. Specific actions are proposed for advocacy,
      communication and dissemination, networks and partnerships, fundraising, policy
      development and implementation, programme implementation and evaluation,
      surveillance and capacity building. The development of the Global Alliance for
      Physical Activity (GAPA) provides a structure for international collaboration.

PMID- 17017291
TI  - Coalitions and networks: facilitating global physical activity promotion.
AB  - This article aims to synthesise the experience of coalitions and networks working
      for physical activity promotion. By introducing the concept of partnerships,
      especially within the Brazilian context, the authors outline the factors that
      comprise a successful partnership, describing key elements, such as, financing,
      membership and methods of empowerment. Agita Sao Paulo, the Physical Activity
      Network of the Americas-RAFA-PANA and Agita Mundo are used as examples. The
      article shows that local, national and global programmes, partnerships and
      networks at all levels are essential to guarantee the success of physical
      activity promotion as a public health strategy.

PMID- 17017292
TI  - Muevete Bogota: promoting physical activity with a network of partner companies.
AB  - In 1998 the mayor's office and the District Institute for Sports and Recreation
      created Muevete Bogota, a physical activity and health promotion programme for
      the capital city of Colombia. Muevete means to move or to be active, and this
      campaign to promote physical activity was designed to improve the health and
      quality of life of the citizens of Bogota through regular physical activity. The
      programme is based on the 1995 recommendations on physical activity of the U.S.
      Centers for Disease Control and Prevention and the American College of Sports
      Medicine (Pate el al, 1995), and was developed in close consultation with the
      Agita Sao Paulo programme in Brazil (Matsudo el al., 2003). Muevete Bogota
      couples a mass media campaign with programmes targeted to change physical
      activity behaviour. The interventions, which are conducted at work sites,
      schools, health care centers and in community settings rely on partnerships
      created among professionals in areas of education and health, business officials
      and personnel, and community members, to deliver the programmes in each of these
      settings and populations. Like many developing countries, Colombia suffers from a
      growing epidemic of chronic diseases. In 1993 35.7% of total mortality in the
      city of Bogota was due to chronic diseases (Espinosa, 1993). In 2002
      cardiovascular diseases accounted for 40.3% of mortality among the population
      aged 60 years or older and 26.8% for persons 45 to 59 years of age. (Cardona,
      2002) Bogota has implemented extensive physical and social environmental changes
      over the last decade, which has increased opportunities for physical activity,
      but sedentary lifestyle continues to be a significant public health problem in
      the city. Programmes such as Muevete Bogota that educate and motivate the
      population to become more physically active appear to be needed to complement the
      underlying environmental and policy changes. Muevete Bogota provides an example
      of successful implementation of a comprehensive multi-sectoral approach to
      physical activity promotion in a large metropolitan area. This model may be used
      as an exemplary effort elsewhere in Latin America and in urban areas in
      developing countries around the world.

PMID- 17017293
TI  - [Duchenne muscular dystrophy: rational basis, state of the art].
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects
      approximately 1 in 3500 male births. Boys with Duchenne have a progressive and
      predictable muscle deterioration: muscles lack dystrophin, a protein essential
      for membrane stability, whose absence induces contraction-related membrane damage
      and activation of the inflammatory cascade leading to muscle failure, necrosis,
      fibrosis. Although DMD is present at birth, clinical symptoms are not evident
      until 2-6 years of age. Initial symptoms include leg weakness, increasing spine
      kyphosis, and a waddle-like gait. Continuous muscle wasting leads to
      progressively weaker muscles, usually leading DMD patients on wheelchair by the
      age of 8-12. Scoliosis develops in 90% of boys who use a wheelchair full-time.
      Progression of muscle degeneration and worsening clinical symptoms lead to death
      in the late twenties from respiratory/cardiac failure.

PMID- 17017294
TI  - [Duchenne muscular dystrophy: perspectives of treatment].
AB  - Although the cloning of the dystrophin gene has led to major advances in the
      knowledge of the molecular, genetic basis of Duchenne Muscular Dystrophy (DMD),
      Becker Muscular Dystrophy (BMD), and other muscular dystrophies, with mutations
      of genes encoding the dystrophin-associated glycoprotein complex, an effective
      therapy is still lacking. This review reports some of the most promising
      pharmacological, molecular and cellular approaches to DMD/BMD. All together,
      these exciting developments are just puzzling work hypothesis whose clinical
      developments is on the way.

PMID- 17017295
TI  - [Iron and performance in elite athletes].
AB  - The negative relationship between performance and iron deficiency anemia is well
      known. There is still debate in the literature on the exercise-induced iron loss
      and if low iron store, even in the absence of frank anemia, can adversely
      affected performance of elite athletes. We analyse the physiologic changes
      induced by strong exercise, the diagnostic problems and therapeutic
      supplementation.

PMID- 17017296
TI  - [Chronic tension-type headache non conventional therapy with manual lymphatic
      drainage].
AB  - Chronic tension-type headache (CTTH) is a disorder with daily or very frequent
      episodes of headache, lasting minutes to days, on 15 or more days a month (180
      days/year) for at least 3 months. CTTH is a painful and common experience that
      negatively influences patient's quality of life. The use of complementary and
      alternative therapies in its treatment is an interesting and growing phenomenon.
      The aim of the present study was to evaluate the outcomes of patients undergoing
      manual lymphatic drainage treatment for CTTH. The findings demonstrate that
      headache patients reported a reduction in pain frequency and intensity.

PMID- 17017297
TI  - [Wegener's granulomatosis: that is the risk of diagnostic hypervaluation].
AB  - Iter for diagnosis of Wegener's granulomatosis is delineated, underling the role
      of ANCA, histological test and the risk of diagnostic hypervalutation.

PMID- 17017298
TI  - [Extrapulmonary sarcoidosis with prevalent liver involvement: a new case and
      review of the literature].
AB  - A few cases of sarcoidosis are associated with progressive liver disease. We
      report a case of sarcoidosis with prevalent hepatic location. This case
      emphasizes the possibility of an organ-specific extrapulmonary presentation of
      sarcoidosis and in this context, outlines the fact that hepatic involvement,
      independent of any pulmonary and/or mediastinal lymph nodes involvement, may be
      more frequent than has been reported up to now.

PMID- 17017299
TI  - [Treatment for Helicobacter pylori in children. Recent advances].
AB  - Helicobacter pylori (H. pylori) is a highly prevalent pathogen considered as an
      aetiological factor for gastric ulcers and gastric cancer. Most children
      colonized by H. pylori are asymptomatic and remain untreated. In symptomatic
      patients, the antibiotic treatment is not 100% effective because of the
      resistance to antibiotics and the imperfect patient compliance. Mono-therapy or
      dual-therapy have a very low efficacy. Dual therapies with bismuth plus one
      antibiotic or two antibiotics for two weeks are as effective as either bismuth
      based or proton pump inhibitor-based triple therapies. Triple therapies were less
      effective than in adults, and proton pump inhibitor-based triple therapies have a
      similar efficacy irrespective of the duration. Recently, a new sequential
      treatment proved to be more efficacious than standard therapies. Recent data
      suggest that probiotics may maintain lower levels of H. pylori in the stomach,
      and in combination with antibiotics, probiotics may decrease adverse effects.
      Probiotics might constitute a low-cost, large-scale alternative solution
      applicable for populations at-risk for H. pylori colonization.

PMID- 17017300
TI  - [Lipase/amylase ratio and liver function tests for the etiological assessment of
      acute pancreatitis: facts and fiction].
AB  - Acute pancreatitis represents the 0.15-1.5% of all diagnoses in the Emergency
      Room. Biliary diseases and alcohol abuse are the two mainly etiological factors
      of this illness in Italy. From a clinical point of view, the course of alcoholic
      and biliary acute pancreatitis is the same; however, because the endoscopic
      retrograde cholangiopancreatography associated with endoscopic sphincterotomy can
      prevent further complications in patients with severe biliary pancreatitis, it is
      important to early recognize the biliary origin of the disease. On the other
      hand, the identification of alcoholic origin of pancreatitis can prevent
      interventional procedures not useful in this kind of patients. In this paper we
      will assess the markers able to early identify the etiology of this acute illness
      such as the liver function tests and the lipase/amylase ratio.

PMID- 17017301
TI  - [Evaluation of liver fibrosis in clinical practice].
AB  - The evaluation of liver fibrosis plays a fundamental role in hepatology. The
      biopsy today remains the reference examination, however in the last years new
      methods for non invasive evaluation of liver fibrosis have been suggested. Their
      improvement could lead to replacement of liver biopsy in the immediate future.

PMID- 17017302
TI  - The personal protective behaviors of college student drinkers: evidence of
      indigenous protective norms.
AB  - Given the prevalence of alcohol consumption and the relative infrequency of harm
      among college students, the authors sought to determine how most college students
      protect themselves from alcohol-related harm. An analysis of the aggregate
      National College Health Assessment data identified a cluster of personal
      protective behaviors that correlated with reduced risk when drinking. Further
      analysis revealed that nearly three-quarters of student drinkers regularly employ
      at least 1 protective behavior, and well over half of the students who use
      protective behaviors routinely employ 2 or more. In addition, the data reveal
      that student drinkers employ situational abstinence, with nearly 7 out of 10
      students reporting that they sometimes or usually refrain from drinking alcohol
      when they socialize. The use of these protective behaviors is a strong predictor
      of safety and harm for college-student drinkers.

PMID- 17017303
TI  - Physical activity is associated with better health and psychological well-being
      during transition to university life.
AB  - The authors investigated vigorous physical activity, psychological well-being,
      and self-reported illness during transition to first-year university life in a
      sample of 175 Canadian undergraduates. At the completion of their first year of
      university study, participants completed retrospective measures assessing
      vigorous physical activity, upper respiratory infectious illness (URI), doctor
      visits, as well as measures of psychological well-being. Based on nationally
      recommended (US Department of Health and Human Services) standards, 61% of
      students reported engaging in adequate levels of vigorous activity during their
      first year at university. The authors found no differences in URIs between
      sufficiently and insufficiently active students. However, insufficiently active
      students scored lower on psychological well-being and were twice as likely to
      have consulted a physician regarding an illness compared with sufficiently active
      students.

PMID- 17017304
TI  - International study of heavy drinking: attitudes and sociodemographic factors in
      university students.
AB  - The authors studied the prevalence of heavy drinking among students in 21
      developed and developing countries using an anonymous survey of 7,846 male and
      9,892 female students aged 17 to 30 years. There were wide variations in the
      prevalence of drinking among countries, and the highest rates of heavy drinking
      (defined as 5 or more drinks for men and 4 or more drinks for women on at least 1
      occasion over the past 2 weeks) were reported in Belgium, Colombia, Ireland, and
      Poland (men), and Ireland and England (women). Heavy drinking was associated with
      living away from home, having a wealthier family background, and having well
      educated parents. Beliefs about the dangers to health of excessive consumption
      were negatively related to heavy drinking. Heavy drinking is a concern among
      students in several countries and is associated with greater affluence.
      Challenging beliefs concerning health risks is a crucial aspect of prevention in
      this population.

PMID- 17017305
TI  - Real men do not read labels: the effects of masculinity and involvement on
      college students' food decisions.
AB  - Consumer literature shows that a decision's degree of personal importance and
      relevance--one's level of involvement in the decision--indicates which type of
      intervention strategy will be effective in influencing consumers' choices. The
      authors surveyed 358 college students at a state university in the western United
      States to test the applicability of involvement on issues of obesity and eating
      habits. They found food decisions to be of greater personal importance and
      relevance to female students than to their male counterparts. The results suggest
      that efforts to address levels of obesity and being overweight among male college
      students must recognize that men's food choices are very much rooted in the
      ideology of what it means to be female and male in contemporary American society.
      The authors advance 5 peripheral-route intervention strategies to augment
      existing cognitive-oriented, information-based intervention programs.

PMID- 17017307
TI  - From probation to prevention: protecting college students and workers from animal
      hazards.
AB  - OBJECTIVE: Our objective was to develop an organized system to assess individual
      and group exposure to animal hazards on a college campus. MAIN POINTS: The scope
      and complexity of college health services continue to expand as campuses confront
      unforeseen exposures and disease entities. Of great concern are students and
      faculty who are exposed to potentially life threatening and other serious
      conditions during their academic work. CONCLUSION: A college health service
      developed an effective animal-hazard surveillance questionnaire that could be
      scanned and analyzed for individual and group exposure to hazards and the
      presence or absence of protective measures. The college then provided appropriate
      preventive services.

PMID- 17017306
TI  - Evidence for significant polydrug use among ecstasy-using college students.
AB  - Ecstasy (MDMA) has been added to the spectrum of illicit drugs used by college
      students. In this study, the authors estimated the prevalence of ecstasy use
      within a large college student sample and investigated the polydrug-use history
      of those ecstasy users. They administered an anonymous questionnaire to college
      students (N = 1,206) in classrooms at a large university in the mid-Atlantic
      United States. The overall student response rate was 91%. Nine percent of the
      sample reported lifetime ecstasy use. Because 98% of ecstasy users had used
      marijuana, the authors compared polydrug use between ecstasy users and
      individuals who had used marijuana but not ecstasy. Ecstasy users, as compared
      with these marijuana users, were significantly more likely to have used inhalants
      (38% vs. 10%), LSD (38% vs. 5%), cocaine (46% vs 2%), and heroin (17% vs 1%) in
      the past year. Significant polydrug use among college student ecstasy users has
      important implications for their substance abuse treatment.

PMID- 17017308
TI  - Perspectives of college students and their primary health care providers on
      substance abuse screening and intervention.
AB  - The authors conducted a needs assessment among students and health-care providers
      of a southwestern university health center with the goal of developing health
      care-provider training addressing substance-abuse screening and intervention.
      They collected data from focus groups of undergraduate students and structured
      interviews and questionnaires with health-care providers. They identified gaps in
      provider and student perspectives on the extent of substance abuse on campus and
      the perceived roles of health-care providers and patients in screening and
      conducting interventions for substance abuse. These findings suggest that
      training for college health-care providers regarding substance-abuse brief
      screening and intervention should emphasize confidentiality of student medical
      records, the importance of nonjudgmental attitudes toward students, and the role
      of the provider as one who is competent and appropriate to address substance
      abuse. Such training should also educate providers about the types of substances
      students are using.

PMID- 17017309
TI  - Predictive modeling: a more creative approach for disease management programs.

PMID- 17017310
TI  - Using predictive modeling to evaluate the financial effect of disease management.
AB  - The objective of this study was to use predictive modeling to evaluate a disease
      management (DM) program's effect on a chronically ill population. Specifically,
      diagnostic cost grouping (DCG) predictive modeling was utilized to measure the
      financial effect of DM in populations of individuals with congestive heart
      failure and coronary artery disease. The literature of current practices
      regarding DM's financial effect measurement was reviewed and critiqued-
      especially with reference to the population-based pre-post method. The time
      period for the present study is three years, and the variables of interest are
      financial metrics. Claims data and DM program-specific data covering the 24-month
      period of 2001 to 2002 and the 24-month period of 2002 to 2003 were analyzed. The
      mean differences between DCG predicted and actual total claims costs in 2002 and
      in 2003 were computed. Inflation factors, based on actual health plan population
      experience for the populations in question, were developed and applied to
      accurately evaluate financial effect. The preliminary findings suggest that a
      study design utilizing DCG predictive modeling in evaluating DM program financial
      impact provides more accurate results compared with the population-based pre-post
      method currently favored by DM companies.

PMID- 17017311
TI  - The issue of medication adherence raises more questions than answers.

PMID- 17017312
TI  - The effect of medication adherence on health care utilization in bipolar
      disorder.
AB  - A retrospective analysis of electronic prescription and medical claims
      representing approximately 1.4 million managed care commercial health plan
      members with mental health benefits was conducted. The effect of patient
      adherence to traditional mood-stabilizer therapy (lithium, valproate,
      carbamazepine, lamotrigine, or oxcarbazepine) for bipolar disorder on mental
      health-related hospitalization was assessed among 1,399 patients (mean age, 42.9
      yr; 66.3% female) studied. Reduced adherence to traditional mood-stabilizing
      therapy (< 80%) in patients with bipolar disorder was associated with
      significantly greater risk of mental health-related, emergency room visits (odds
      ratio, 1.98; 95% confidence interval, 1.38-2.84) and inpatient hospitalizations
      (odds ratio, 1.71; 95% confidence interval, 1.27-2.32), even after adjusting for
      age, gender, and comorbidity.

PMID- 17017313
TI  - Comparison of costs associated with the use of etanercept, infliximab, and
      adalimumab for the treatment of rheumatoid arthritis.
AB  - A retrospective study of health plan costs related to rheumatoid arthritis (RA)
      revealed that etanercept was associated with the lowest drug and outpatient costs
      to the health plan than infliximab and adalimumab. Compared with etanercept,
      infliximab was related to 55% higher postindex RA-related monthly total health
      care costs paid by the health plan, based on adjusted analyses (95% confidence
      interval, 1.47-1.64). Patients receiving adalimumab had 12% higher costs (95%
      confidence interval, 1.04-1.21). The study showed the average dispensing dose
      increase was greatest for infliximab (17.4%) and least for etanercept (4.1%).

PMID- 17017314
TI  - Say it in English.

PMID- 17017315
TI  - Tackling depression in the elderly is not easy.

PMID- 17017316
TI  - New hand sanitizers: be sure to use care.

PMID- 17017317
TI  - Have you ever cared for a patient whose recovery was medically unexplainable?

PMID- 17017318
TI  - Forensic evidence. Preserving the clinical picture.

PMID- 17017319
TI  - Tongue tissue may offer option in urethral repair.

PMID- 17017320
TI  - How to fine-tune your PICC care.

PMID- 17017321
TI  - Back to basics with O2 therapy.

PMID- 17017322
TI  - Antibiotics.

PMID- 17017323
TI  - ST segment changes clue you in to injury location.

PMID- 17017324
TI  - Where spirituality and healthcare meet.

PMID- 17017325
TI  - The benefits of having a travel buddy.

PMID- 17017326
TI  - Adventures along the way.

PMID- 17017327
TI  - Power in numbers.

PMID- 17017328
TI  - Measuring retirement income adequacy: calculating realistic income replacement
      rates.

PMID- 17017329
TI  - The death of professionalism.

PMID- 17017330
TI  - A case report of neuroleptic malignant syndrome without fever in a patient given
      aripiprazole.
AB  - Neuroleptic malignant syndrome (NMS) is a rare disorder seen most often in
      patients exposed to antipsychotic medications. This syndrome is generally
      manifested by hyperthermia, muscle rigidity, autonomic instability, altered
      mental status, tremors, elevated serum creatinine phosphokinase and leucocytosis.
      It was first described by Delay during the 1960s. It is considered a medical
      emergency and is fatal if not promptly addressed. It is clinically relevant not
      only to psychiatrists but all clinicians since patients taking neuroleptics are
      seen by physicians from virtually every specialty. Relevant studies report a
      mortality rate of 10-20%. Conditions that share some features of NMS but have
      different treatment regimens include serotonergic syndrome, lethal catatonia,
      malignant hyperthermia, infections and various heat disorders. The importance of
      recognition and prompt intervention can not be overemphasized. Fever is a
      predominant symptom in NMS. The authors present an unusual case of NMS in a
      schizophrenic patient without fever who had been on aripiprazole. To date, there
      are only three possible reported cases of NMS related to aripiprazole. This case
      report serves to remind clinicians of the essential features in the diagnosis and
      management of NMS.

PMID- 17017331
TI  - Ethnic differences in fasting glucose, insulin resistance and lipid profiles in
      obese adolescents.
AB  - Children and adolescents with obesity are increasingly referred to the pediatric
      endocrinology clinic at OU Children's Hospital for evaluation and initiation of
      preventive measures. During the summer of 2004 we conducted a retrospective
      review of cases to determine the prevalence of fasting insulin resistance and
      dyslipidemia; to study associations and differences due to ethnic background; and
      compare values with similar patients seen at four Indian Health Service clinics.
      We observed the highest prevalence of dyslipidemia in Caucasian youth. The
      prevalence of high fasting glucose and mean glucose values were higher in the
      obese Native American youth than in African Americans or Caucasians. The elevated
      glucose levels in young Native Americans may be associated with their increased
      risk for type 2 diabetes compared to other races; but Caucasians are more prone
      to dyslipidemia. Effective methods are needed to detect, prevent and treat
      diabetes and cardiovascular risk in children and adolescents.

PMID- 17017332
TI  - Admitting a patient "to" observation or "for" observation--what is the
      difference?
AB  - Coding and billing of a patient placed in "observation" status can be confusing,
      especially in a busy Emergency Department. If physicians know the rules related
      to observation status, they can avoid denials or accusations of false claims.
      Documenting either "admit to observation" or "admit for observation" can be
      interpreted differently for admission status and billing services. From a billing
      prospective, writing "admit for observation" would be interpreted as an inpatient
      admission (if the documentation throughout the medical record is consistent with
      inpatient status). If the order states "admit to observation," this normally
      would be interpreted as an order for outpatient observation. Physicians are
      encouraged to write admission orders that clearly state the level of services
      intended; for example, wording such as "place in outpatient observation" or
      "admit as inpatient," to clearly convey the physician's intent.

PMID- 17017333
TI  - Concerning the First International Congress on Work-related Illnesses--Milan 9-14
      June 1906: Success--News--Reports--Motions.

PMID- 17017334
TI  - Some contributions from the doctor of the miners in the Simplon tunnel: The most
      human of victories. The Provinces of Italy to the Simplon tunnel. The family of
      the miner at Simplon. 1906.
AB  - Similarly to Daniele Pometta (1869-1949) on the northern front, Giuseppe Volante
      (1870-1936) from Turin, a valid clinician and hygiene expert was the field doctor
      for the firm of Brandt, Brandau e C., on the southern part of the Simplon tunnel
      for the whole period of its excavation (1898-1906). He meticulously organised and
      carried out with determination the main mission entrusted him which was to
      prevent the hookworm epidemic which a mere twenty years earlier had cast its
      shadow over the St. Gotthard tunnel. Volante also authoritatively directed the
      first aid post and the hospital that the company built at Nante. Evidence of
      Volante's vast medical experience was seen in the scientific works he published
      as well as in a report published in the acts of the International Conference on
      Work-related Illnesses (Volante, 1906a) and then in a comunication at No. 3
      Italian Congress on Work-related Illnesses in Turin (Volante, 1911). There are
      three interesting works reproduced here (Volante, 1906b-c-d) which are
      substantially aimed at a broad readership and which clearly illustrate the work
      carried out, the experience gained and also the author's cultural background.
      Volante's remarks and the data he supplies are "official" but show no sign of
      partiality; they convey the grandness of the work he contributed towards creating
      and in some ways also the "generosity" of the company towards the labour force
      who "only" went on strike three times for better pay, fewer hours and improved
      working conditions. Volante's opinion on the low morbidity and mortality of the
      workers is certainly motivated although it is still relative, first and foremost
      because he had the tragedy of the St Gotthard as a yardstick, but also because it
      was swayed by the idea, widespread at the time, of fatalism about the potentially
      negative effects of the type of work. During the International Conference in 1906
      Violante was awarded a gold medal for the work he had conducted, and for three
      years afterwards he worked under Luigi Devoto (1864-1936) in Milan. After that,
      he returned to his native Turin where he practised urology. According to his
      direct descendents, he died aged 64 from respiratory insufficiency the causes of
      which included a "pneumoconiosis" diagnosed by Prof. Quarelli (1881-1954), a
      renowned doctor of work-related illnesses, which he had obviously contracted in
      the period when he had been the doctor of the miners (Gius Volante, 2006).

PMID- 17017335
TI  - OSH and globalisation, challenges for today.
AB  - Globalisation is a phenomenon that concerns all countries in the world at every
      level: economic, of course, but also political and cultural. It is hard to see
      any alternative to the dominant market economy model, which is asserting itself
      as the only way towards wealth and value creation. And within this model, it is
      free enterprise, generating jobs and boosting consumption, that is the
      unequivocal model of development for the world's economies. How can we then
      address the question of occupational safety and health (OSH) within the context
      of globalisation? How can we ensure that worker protection is not relegated to
      the status of a secondary concern? Safety and health inequalities between
      countries are such that it seems difficult to state without being hypocritical
      that OSH is already a value in the globalised world. The number of occupational
      accidents and diseases remains at a disturbingly high level, especially in
      developing countries. The sectors most affected are traditionally heavy industry,
      agriculture, mining and construction. In these sectors, there is so much
      economically and financially at stake that the obligation to protect workers'
      health is often viewed as a constraint, at odds with the requirement of immediate
      profitability. I sincerely believe that the prevention of occupational risks
      really has a different meaning depending on whether you work in an SMU or a large
      corporation. And, of course, depending on whether you live in a country with a
      high level of social protection, or one where social insurance is considered a
      luxury only for the richest. And the globalisation of trade is tending to further
      increase this gap. We have therefore elected to state that occupational safety
      and health "cannot be taken for granted" in a globalised world and that there are
      challenges facing all those, whether officials in institutions or managers of a
      business, who believe that working in a decent environment is a non negotiable
      demand.

PMID- 17017336
TI  - The changing nature of work: workplace stress and strategies to deal with it.
AB  - Workplace stress is costing the developed and developing world roughly between 5
      10% of Gross National Product per annum in sickness absence, premature retirement
      due to ill health and lost productive value in terms of services and products. In
      addition, it is costing the health services of countries an additional burden in
      terms of treatment and incapacity benefits. A three prong approach to stress
      management and prevention is provided, exploring primary interventions (risk
      assessment), secondary interventions (training and development) and tertiary
      interventions (stress counselling and support).

PMID- 17017337
TI  - Aging and globalization.

PMID- 17017338
TI  - Towards a longer and better working life: a challenge of work force ageing.
AB  - The aim of this overview is to describe the background of work force ageing and
      its consequences in the society, to introduce concepts for the solutions, to
      emphasize the actions needed, to point out the new challenges for occupational
      health, to review the targets of work life improvements, and to highlight the new
      innovations needed. Work life must be lengthened for the sake of society. Early
      retirement and low employment rates of 55-64-years old employees make the
      dependency ratios an increasingly heavy burden. New innovations and concepts like
      promotion of work ability and age management training have been effective tools
      for the increase of employment rates and decrease of age discrimination in
      Finland. The increase of the prevalence and incidence rates of work-related
      symptoms and diseases during ageing is a serious challenge for occupational
      health experts. The better adjustments of the working life with the individual
      health is a crucial element for a longer career. The European working life has
      not improved markedly for workers over 45 years between 1996 and 2000. Therefore,
      evidence based concepts should be widely and effectively implemented and new
      innovations created. A better co-operation between macro-, meso and micro levels
      is necessary, social partners should create mutual programmes in work places and
      a new deal is needed between the generations. Life course approach combines the
      needs and possibilities of different generations. Age management takes into
      consideration the different strengths of the diverse work force.

PMID- 17017339
TI  - Social protection sustainability, prolongation of working life and greater
      participation of women in the labour market.
AB  - One of the greatest problems of European societies is the financial
      sustainability of social protection systems in Europe. Together with Japan,
      Europe has the highest levels of ageing population in the world. This concern
      explains the reiterated insistence of the European Commission and the OECD
      regarding the reforms that governments should undertake. In this paper, reference
      is made to two of these reforms: prolonging of working life and a greater
      participation of women in the labour market.

PMID- 17017340
TI  - Psychological well-being and work attitudes across a range of employment status
      categories.

PMID- 17017341
TI  - Emerging aspects of psychosocial risks: violence and harassment at work.
AB  - In the last twenty years, psychosocial risks have become crucial in Occupational
      Health. Particularly, there is an increasing interest about psychological and
      physical violence at the workplaces. Psychological violence (mobbing or workplace
      bullying) is described as a situation in which the person has been the victim of
      negative acts directed to the person and work, with offences, discriminations and
      isolation. Physical violence at work, still underestimated in many parts of the
      world, is becoming a topical subject both for its frequency and its pathogenic
      potential and consist of violence among workers (internal violence) and between
      workers and external persons (external violence). Examples of external violence
      are bank robberies, which are prevalent in many European countries, particulary
      in Italy. The costs of psychological and physical workplace violence are very
      high at all levels; individual, for the implication of violence for health and
      quality of life as well as organizational, for the increase of absenteeism,
      turnover and health care demands and claims. The Medical Centre for Occupational
      Stress and Harassment (CDL) of the "Clinica de Lavoro Luigi Devoto" was set up in
      1996 with a day-hospital service for the diagnosis, rehabilitation and prevention
      of work related psychological diseases. From its opening, about 5000 patients
      have been examined.

PMID- 17017342
TI  - The longer-term health impact of war service.

PMID- 17017343
TI  - Evaluation of scientific evidence in law, adjudication and policy: when
      occupational health takes the witness chair.
AB  - Health and medical knowledge are essential to the resolution of disputes in law
      and administrative applications (such as workers' compensation) and provide
      essential input into public policy decisions. There are no socially agreed-upon
      rules for the application of this knowledge except in the law. On a practical
      level, the legal system lacks the capacity to evaluate the validity of knowledge
      as evidence and therefore relies heavily on expert opinion. Over the last 30
      years, an approach called "critical appraisal" and "evidence-based medicine"
      addressed a similar problem in medical practice and established norms for the
      acceptance of evidence in clinical medicine. A similar evidence-based framework
      may be possible for applying knowledge of health and medicine to dispute
      resolution in the law. One critical issue is how to apply scientific evidence
      when the standard is "more likely than not" rather than scientific certainty.
      Another is how the generalizations drawn from epidemiology and population-based
      sciences are interpreted and individualized, as they must be, for the case at
      hand. A related issue is how risk is interpreted for an individual after the
      fact, when conventional probability treats risk before the fact and conventional
      biostatistics applies primarily to a population. This emerging approach is called
      "evidence-based medical dispute resolution".

PMID- 17017344
TI  - Prioritizing future resources for epidemiologic research on old and newly
      emerging occupational hazards.
AB  - BACKGROUND: Inevitably, occupational epidemiologists must decide when and how to
      shift research attention and resources from investigations of old, established
      health hazards to a focus on newly emerging potential risk factors. As yet
      unknown occupational health consequences of burgeoning worldwide technologies,
      such as the microelectronics industry, and increasing recognition of the
      importance of common, yet non-traditional occupationally-related health effects,
      such as musculoskeletal disorders in office workers, give strong impetus for
      embarking in new directions. However, there remains much to be learned from
      continued investigation of well-established occupational hazards, such as
      asbestos, benzene, and lead. OBJECTIVES: A rational strategy for planning future
      research will need to consider optimizing resources. CONCLUSIONS: The following
      suggestions are offered. 1) First and foremost, occupational risk factors are
      most directly, and arguably most validly, identified by studying workers in well
      defined cohorts, ideally when exposures are adequately characterized. To this
      end, industry-based cohort studies should be given priority, at least for older
      hazards, over population-based case-control and surveillance designs. 2) Defined
      cohorts with extensive exposure and health outcome data should continue to be
      followed, as resources permit; 3) Launching cohort studies for potential new
      hazards should incorporate extensive exposure assessments at the outset, and
      should preferentially select inception cohorts of newly hired workers. Valid
      biomarkers of pre-clinical disease will be especially valuable in this regard. 4)
      Capitalizing on new technological advances in exposure assessment, clinical
      medicine, molecular genetics should be encouraged

PMID- 17017345
TI  - Work-related musculoskeletal disorders: is the burden equitably distributed?

PMID- 17017346
TI  - Health risks of exposure to non-ionizing radiation--myths or science-based
      evidence.
AB  - INTRODUCTION: The non-ionizing radiation (NIR) contains large range of
      wavelengths and frequencies from vacuum ultraviolet (UV) radiation to static
      electric and magnetic fields. Biological effects of electromagnetic (EM)
      radiation depend greatly on wavelength and other physical parameters. OPTICAL
      RADIATION: The Sun is the most significant source of environmental UV exposure,
      so that outdoor workers are at risk of chronic over-exposure. Also exposure to
      short-wave visible light is associated with the aging and degeneration of the
      retina. Especially hazardous are laser beams focused to a small spot at the
      retina, resulting in permanent visual impairment. ELECTROMAGNETIC FIELDS:
      Exposure to EM fields induces body currents and energy absorption in tissues,
      depending on frequencies and coupling mechanisms. Thermal effects caused by
      temperature rise are basically understood, whereas the challenge is to understand
      the suspected non-thermal effects. Radiofrequency (RF) fields around frequencies
      of 900 MHz and 1800 MHz are of special interest because of the rapid advances in
      the telecommunication technology. The field levels of these sources are so low
      that temperature rise is unlikely to explain possible health effects. Other
      mechanisms of interaction have been proposed, but biological experiments have
      failed to confirm their existence.

PMID- 17017348
TI  - Epidemiology in risk management for chemicals.
AB  - Risk management is the process by which choices are made between alternative
      actions or policies according to the likelihood of beneficial or adverse
      outcomes. It entails an assessment of the potential risks and benefits associated
      with each possible option, and the application of value judgements to decide
      which option should be chosen. Informal risk management for chemicals, a
      distinction is made between hazard (a potential adverse effect of the substance)
      and risk (the probability that that a hazard will be realised given the
      circumstances and extent of exposure to the substance). Where there is
      uncertainty about the existence of a hazard or about the level of risk associated
      with an exposure, this must also be taken into account. Of the various measures
      of risk, the two that are most relevant to risk management are the individual
      attributable risk and the population attributable risk. Assessment of risk
      entails the identification and characterisation of hazards, and estimation of the
      risks associated with the exposure circumstances that will follow from different
      policy options. Examples are given of the way in which epidemiology can
      contribute to this process, and also to checking that the outcomes of decisions
      in risk management accord with what was predicted by underpinning risk
      assessments. The strengths and limitations of epidemiology as a tool in risk
      management are discussed.

PMID- 17017349
TI  - Refining the focus of construction injury surveillance.
AB  - We conducted two studies of construction injury occurring at Denver International
      Airport (DL4), whose construction required 31 million work hours. Initially we
      conducted a retrospective cohort study that allowed estimation of injury and
      workers' compensation (WC) payment rates for strata such as size of employer and
      type of work; risk factors were also estimated. The second study examined written
      injury reports for 4,000 injuries at DIA. We modified Haddon's matrix to classify
      factors contributing to injury. We identified 108 factors within 4 broad
      categories: human, object, environment and organization. This approach provided
      information on rates at which each factor contributed to injury and the WC
      payment rates for each factor. A study shortcoming was that injury reports varied
      in completeness and quality. In a third ongoing study, to compensate for the
      shortcomings of injury reports, particularly to improve consistency and
      completeness of data, we designed a worker questionnaire completed immediately
      after injury, which included questions specific to hazards associated with each
      type of injury. Upon completion, the interviewer (a safety professional) uses the
      modified Haddon's matrix to note contributors to the injury and explain briefly
      the reasons for each notation. This requires the interviewer to consider a full
      set of possible factors and determine whether they contributed to injury. This
      process elicits richer data and places specific factors within the four higher
      level categories. This process confer advantages on both contractors and
      researchers. Contractors can become immediately aware of contributing factors and
      ameliorate them quickly. The data can also be used in post hoc analysis of injury
      etiology. Moreover, the data are sufficiently flexible and complete that they can
      be coded into schemes describing sequences of events leading to injury, as well
      as those simply identifying factors contributing to injury. Haddon's matrix is
      invaluable in such analysis because it leads to a fuller understanding of the
      origins of the most proximate contributors to injury than would otherwise occur.
      Particularly for contractors and owners with significant safety infrastructures,
      this approach may be attractive, because it allows for more complete and quicker
      correction of specific hazards and, with systematic evaluation, recognition of
      more general safety concerns present on many construction sites.

PMID- 17017350
TI  - Recent developments in human biomonitoring: non-invasive assessment of target
      tissue dose and effects of pneumotoxic metals.
AB  - Tobacco smoke and polluted environments substantially increase the lung burden of
      pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a
      better understanding of the early events between exposure to inhaled toxicants
      and the onset of adverse effects on the lung, the characterization of dose at the
      target organ would be extremely useful. Exhaled breath condensate (EBC), obtained
      by cooling exhaled air under conditions of spontaneous breathing, is a novel
      technique that could provide a non-invasive assessment of pulmonary pathobiology.
      Considering that EBC is water practically free of interfering solutes, it
      represents an ideal biological matrix for elemental characterization. Published
      data show that several toxic metals and trace elements are detectable in EBC,
      raising the possibility of using this medium to quantify the lung tissue dose of
      pneumotoxic substances. This novel approach may represent a significant advance
      over the analysis of alternative media (blood, serum, urine, hair), which are not
      as reliable (owing to interfering substances in the complex matrix) and reflect
      systemic rather than lung (target tissue) levels of both toxic metals and
      essential trace elements. Data obtained among workers occupationally exposed to
      either hard metals or chromium (VI) and in smokers with or without chronic
      obstructive pulmonary disease (COPD) are reviewed to show that--together with
      biomarkers of exposure--EBC also allows the simultaneous quantification of
      biomarkers of effect directly sampled from the epithelial lining fluid, thus
      providing novel insights on both kinetic and dynamic aspects of metal toxicology.

PMID- 17017351
TI  - Nurses' health, age and the wish to leave the profession--findings from the
      European NEXT-Study.
AB  - BACKGROUND AND OBJECTIVES: In many industrialised countries the number of workers
      with low health is expected to increase in the nursing profession. This will have
      implications for occupational health work in health care. The European NEXT-Study
      (www. next-study. net, funded by EU) investigates working conditions of nurses in
      ten European countries and provides the opportunity to evaluate the role of
      health with respect to age and the consideration of leaving nursing. METHODS:
      26,263 female registered nurses from Belgium, Germany, Finland, France, England,
      Italy, Netherlands, Poland and Slovakia were eligible for analysis. RESULTS: In
      most countries, older nurses considered leaving the profession more frequently
      than younger nurses. 'Health' was--next to 'professional opportunities' and 'work
      organisational factors'--strongly associated with the consideration of leaving
      nursing. However, more than half of all nurses with low health wanted to remain
      in the profession. This group reported rather positive psychosocial working
      conditions--but also the highest fear for unemployment. CONCLUSIONS: The findings
      indicate that 'the nurse with low health' is reality in many health care
      settings. Both positive supporting working conditions but also lack of
      occupational alternatives and fear of unemployment may contribute to this.
      Current economic, political and demographic trends implicate that the number of
      active nurses with low health will increase. Occupational health surveillance
      will be challenged by this. But NEXT findings implicate that prevention also will
      have to regard work organisational factors if the aim is to sustain nurses'
      health and to enable nurses to remain healthy in their profession until
      retirement age.

PMID- 17017352
TI  - Risks of occupational exposure to optical radiation.
AB  - During the past 40 years a wide body of biomedical research has been conducted to
      understand the factors which influence injury to optical radiation-particularly
      with respect to the eye. A primary motivation for much of this research has been
      the advent of lasers, since focal damage of the retina from a collimated beam
      exposure is possible at some distance. A wide range of research studies provided
      the basis for establishing human exposure limits for ultraviolet and infrared
      radiation as well as for intense visible light. The International Commission on
      Non-Ionizing Radiation Protection (ICNIRP) has published guidelines for human
      exposure, and these are available at no cost from the ICNIRP website (http://www.
      icnirp.org). Laser Maximum Permissible Exposure (MPE) limits used in
      international safety standards, such as those of the International
      Electrotechnical Commission (IEC) are based upon ICNIRP guidelines. Practical
      laser safety standards and regulations have evolved to promote the safe design
      and use of laser products. As a result of newer laser applications and increased
      knowledge of the biological effects, MPEs have been revised a number of times.
      Despite the existence of safety standards and regulations, accidental eye
      injuries from lasers still occur. Accidental exposure to welding arcs and intense
      lights occur more fequently, but the consequential loss of vision is much less,
      with permanent effects rare. Accidental human exposure information also adds to
      our understanding of ultraviolet, blue-light and laser induced retinal injury.
      Accidents are most frequently attributed to the lack of understanding of hazards
      and a failure to follow established safe work practices.

PMID- 17017353
TI  - Mobile phones. precautionary options.
AB  - Mobile phones have been in use for over two decades and are ubiquitous in the
      western world for at least ten years. There has been scientific interest and
      public concern about the possibility of adverse health effects from this
      relatively new use of non-ionising electromagnetic energy both at the level of
      the handset and the base station. The proliferation of base transmitter stations
      in the early 1990's caused a resurgence of interest in the possible health
      effects of low level RF in general and several significant studies investigated
      the issue generally using broadcast transmitters as a more predictable source of
      exposure. Handsets, although of much lower power are closely coupled to the users
      body and deserve special attention, which they have received. From this research,
      a high level of assurance of safety has emerged and this is reflected in secure
      international exposure standards allowing more or less unrestricted use of the
      technology from a public health point of view. Nonetheless, some research remains
      unsettled, the science is incomplete in some areas and in the minds of some the
      unknown provides an uncomfortable level of risk. This debate is unlikely to see
      an early resolution and so precautionary approaches are increasingly supported.
      There are a wide range of actions, which have been regarded as precautionary, but
      ultimately minimisation of public exposure is likely to be the only strategy
      which could provide a benefit if any risk is later found. There are practical
      ways of achieving this, but not all proposed strategies seem to recognise them.

PMID- 17017354
TI  - The development of clinical prediction guides requires reproducible decision
      making outputs: a field study.
AB  - BACKGROUND: The decisions taken by occupational physicians (OPs) generally show
      low reproducibility and reflect some uncertainties linked to the decision making
      process. AIM: The aim of the study was to evaluate the variability of different
      OP decisions in order to assess their reproducibility, which is regarded as a
      quality factor of the professional practice. METHODS: 4 OPs examined the records
      of 100 selected hospital workers with impaired health conditions in order to take
      decisions about job fitness, advice to workers, referral to clinical physician,
      need for further investigations, report of occupational disease and
      recommendation for the general practitioner. The variability of inter-individual
      decision was measured by percent agreement and Cohen's kappa test. RESULTS: After
      accounting for variability expected by chance, the agreement among decisions on
      job fitness ranged from fair to substantial, but high variability was observed
      for most other assessments. CONCLUSION: The observed inter-individual variability
      for some decisions taken by different OPs represents a crucial aspect to be dealt
      with, as the reproducibility of medical decisions is indispensable for the
      clinical prediction guides to be built and adopted for improving the practice.

PMID- 17017355
TI  - The new structure and contents of employers' juridical responsibility for
      workers' health and safety in the post-industrial system.
AB  - 1. The enlargement of the labour law application area in the post-industrial
      system. 2. The enormous growth of differences in productivity between workers and
      its consequences on the employer's safety obligation. 3. Depressive disorders as
      a typical professional risk in the post-industrial system and the employer's
      prevention responsibility. 4. Harassment in the work-place as a typical
      pathologic consequence of the de-standardization of jobs. The specific employer's
      prevention responsibility in this field. 5. A conclusive remark.

PMID- 17017356
TI  - Integrating occupational health, safety and worksite health promotion:
      opportunities for research and practice.
AB  - BACKGROUND: There is emerging evidence that coordinating and integrating worksite
      health promotion and occupational health and safety enhances the effectiveness of
      efforts to promote and protect worker health, and growing attention
      internationally to the importance of integrating worksite health promotion and
      occupational health and safety. OBJECTIVES: (1) To present the rationale and
      scientific evidence for coordinating and integrating worksite health promotion
      and occupational health and safety as a means of enhancing the effectiveness of
      efforts to promote and protect worker health; and (2) to discuss recommendations
      for research priorities and future directions. METHODS: Review of the literature,
      drawing mainly on studies from the United States and Europe. RESULTS: The
      strongest evidence available supports the efficacy of this intervention model in
      promoting smoking cessation, particularly among blue-collar workers; some
      evidence additionally indicates significant effects for other health behaviors.
      Little evidence is available to date documenting the impact of these programs on
      occupational health and safety outcomes. CONCLUSIONS: Priority research
      directions include: social epidemiological research to identify key work-related
      factors associated with hazardous occupational exposures and risk-related
      behaviors, and to identify the underlying causes of social disparities in worker
      health; methods development research aimed at developing both appropriate
      measurement tools and new intervention approaches; efficacy and effectiveness
      studies to examine the effects of integrated interventions on both occupational
      health and safety outcomes as well as health behavior changes; assessments of the
      process of intervention implementation, including intervention implementation
      evaluation, cost assessments, and process-to-outcome assessments; and
      dissemination and durability studies, to identify strategies to promote the
      sustainability and dissemination of evidence-based programs.

PMID- 17017357
TI  - The stress-disequilibrium theory: chronic disease development, low social
      control, and physiological de-regulation.
AB  - The Stress-Disequilibrium Theory is based on a new generalized analytic three
      level model based on thermodynamics to describe the process of physiological risk
      development. This approach explains how low social control could cause chronic
      disease through chronic de-regulation of our highly integrated physiological
      systems. Could low external social control lead to low internal physiological
      control: i.e. compromised self-regulation--and then disease? The theory
      implicitly explores the evidence for the physiological causes of chronic
      diseases, including cardiovascular diseases, at a high level (i.e. a non
      reductionist level) and in a unifying manner--to provide a potentially easier
      linkage to the broad social policy consequences implied by the global economy.
      Evidence from our own recent Heart Rate Variability monitoring and job strain
      research (5) is presented which assesses the effect of low control on autonomic
      regulation on the heart. The theory is consistent with the Demand/Control Model,
      and could be considered its underlying theoretical explanation.

PMID- 17017358
TI  - Cardiovascular risk as a paradigm of the negative consequences of stress at work:
      a large amount of data and huge problems.
AB  - The relation between stress and coronary diseases is controversial. Both positive
      and null or negative results are equally obtained. An explanation of this can be
      that the most widely used stress questionnaires are not able to collect all the
      factors that constitute stress perception. Indeed, from a clinical and
      experimental perspective, the stress/coronary diseases relation is evident. More
      consistent results are obtained between coronary diseases and socio-economic
      status. In order to cover all the social factors and describe them better, a new,
      purely theoretical contribution is then introduced: social capital. This is a
      more sophisticated version of social cohesion, social integration and social
      support. Finally, for the future, the interdisciplinary method is recommended for
      health surveillance in the workplace.

PMID- 17017359
TI  - Work and cardiovascular disease.

PMID- 17017360
TI  - Flexibility of working hours in the 24-hour society.
AB  - The 24-hour Society undergoes an ineluctable process towards a social
      organisation where time constraints are no more restricting human life. The
      borders between working and social times are no more fixed and rigidly
      determined, and the value of working time changes according to the different
      economic and social effects you may consider. Shift and night work, irregular and
      flexible working hours, together with new technologies, are the milestone of this
      epochal passage. What are the advantages and disadvantages for the individual,
      the companies, and the society? What is the cost/benefit ratio in terms of health
      and social well-being? Coping properly with this process means avoiding a passive
      acceptance of it with consequent maladjustments at both individual and social
      level, but adopting effective preventive and compensative strategies aimed at
      building up a more sustainable society. Flexible working times now appear to be
      one of the best ways to cope with the demands of the modern life, but there are
      different points of view about labour and temporal 'flexibility" between
      employers and employees. For the former it means a prompt adaptation to market
      demands and technological innovations; for the latter it is a way to improve
      working and social life, by decreasing work constraints and increasing control
      and autonomy. Although it can be easily speculated that individual-based
      'flexibility" should improve health and well-being, and especially satisfaction,
      whereas company-based flexibility" might interfere negatively, the effective
      consequences on health and well-being have still to be analysed properly.

PMID- 17017361
TI  - Occupational health and general practice: from opportunities lost to
      opportunities capitalised?
AB  - BACKGROUND AND AIM: Western populations are in the middle of the epidemiological
      transition of chronic diseases. Care of patients with chronic disease is directed
      at optimising life expectancy and quality of life. Daily and social functioning,
      including paid work are part of the treatment objectives. Yet, advice for and
      support in work related coping with chronic diseases, and collaboration with
      occupational health are not--yet--part of routine curative medical care
      procedures. This is also the case in general practice, where most patients with
      chronic conditions are treated. This 'blind spot' signals a generic lost
      opportunity in optimizing the care of patients with chronic disease. This paper
      analyses from empirical data the importance of integrating work-related advice
      and support in general practice and explores potential evidence of the benefits
      this provides for patients: the opportunities that can be capitalised through
      better interaction between occupational physicians (OP) and general practitioners
      (GP). METHODS: The paper is based on a review of three sources: (i) Epidemiology
      of chronic diseases: the Nijmegen Continuous Morbidity Registration; (ii) The
      relevant guidelines of the Dutch College of General Practitioners; (iii) Studies
      of work-related implications of asthma and COPD management of GPs of the Nijmegen
      centre of Evidence-Based Practice. RESULTS: Chronic diseases like cardiovascular
      disease, diabetes mellitus, COPD and asthma dominate general practice and lead
      annually to a large number of consultations. Although a majority of patients are
      65 years or older--in particular for the first three diseases--GPs also care for
      a substantial number of under-65 years old. General practice guidelines for these
      disorders advocate care directed at normal functioning but do not systematically
      address functioning in the working place. Analysis of work-related functioning in
      case of chronic respiratory diseases, however, highlight that work-related
      factors and circumstances play an important role in patients' coping strategies.
      Patients tend to ignore negative effects of their workplace on their physical
      condition and as a consequence suffer undue limitations. Despite these work
      related risks, COPD patients who were in paid employement perceived higher
      quality of life than COPD patients who were disabled for work, but had similar
      disease severity (airway obstruction). Interestingly, a programme of patients'
      self-management of asthma resulted, in comparison to GP-supervised usual care in
      a substantial and lasting reduction of asthma related absence from work and other
      social-daily activities. CONCLUSIONS AND DISCUSSION: All consultations with
      employees with a chronic (respiratory) disease can be considered as opportunities
      to supervise work-related implications of the disease. Patients value their
      ability to work but frequently apply inefficient coping through ignoring the
      implications of their circumstances for their disease. A more efficient coping
      can probably be achieved through a more active involvement of patients in
      managing their own disease. Guidelines--like the Dutch College of General
      Practitioners'--have developed into a sophisticated and generally respected
      system of guidance of patient care. Explicit emphasis of management in relation
      to the workplace may present a logical opportunity to capitalise on.

PMID- 17017362
TI  - The occupational physician and chemical disasters: old problem, new threats.
AB  - Chemical disasters continue to occur, in spite of significant progress in process
      engineering, industrial hygiene practices, and improved enforcement of health and
      safety legislation. In addition to the ever-present risk of unintentional
      incidents, recent geopolitical events have raised the specter of chemical
      terrorism. Terrorists or even disgruntled employees may exploit lapses in
      chemical plant security and ready access to large quantities commodity chemicals,
      capable of causing great harm to the population if suddenly and unexpectedly
      released. Occupational physicians, who are uniquely equipped to understand the
      health hazards associated with industrial chemicals should be involved in
      prevention of planning for, and response to chemical disasters. Measures for
      improving preparedness include training and collaboration, not only with plant
      health and safety personnel but also with public safety and health care
      providers, through drills and assessment of needs and capacities. Occupational
      physicians should be aware that communications and other systems often fail in
      disasters, requiring multiple alternatives. Likewise, occupational health
      specialists should be prepared to deal with mass casualties, including
      psychological casualties which may be difficult to distinguish from those of
      organic etiology. Chemical disaster preparedness is an urgent and demanding
      responsibility for occupational physicians everywhere.

PMID- 17017363
TI  - Low-cost risk reduction strategy for small workplaces: how can we spread good
      practices?
AB  - Recent advances in health risk reduction approaches are examined based on inter
      country networking experiences. A noteworthy progress is the wider application of
      low-cost improvements to risk reduction particularly in small enterprises and
      agriculture in both industrially developing and developed countries. This is
      helped by the readiness of managers and workers to implement these improvements
      despite many constraints. Typical improvements include mobile racks, simple
      workstation changes, screening hazards, better welfare facilities and teamwork
      arrangements. In view of the complex circumstances of work-related health risks,
      it is important to know whether a low-cost strategy can advance risk reduction
      practices effectively and what support measures are necessary. It is confirmed
      that the strategy can overcome related constraints through its advantages. Main
      advantages lie in (a) the facilitation of improved practices in multiple
      technical areas, (b) the strengthening of realistic stepwise risk reduction, and
      (c) the enhanced multiplier effects through training of local trainers. Action
      oriented risk assessment tools, such as action checklists and low-cost
      improvement guides, can encourage risk-reducing measures adjusted to each local
      situation. It is suggested to spread the low-cost risk reduction strategy for
      improving small workplaces in diversified settings with the support of these
      locally tailored tools.

PMID- 17017364
TI  - The contribution of occupational risks to the global burden of disease: summary
      and next steps.
AB  - BACKGROUND: The Comparative Risk Assessment (CRA) project of the World Health
      Organization (WHO) assessed worldwide mortality and morbidity in the year 2000
      resulting from exposures to selected occupational hazards. This article
      summarizes findings of the WHO CRA project, presents the estimates of the
      International Labor Organization (ILO) for total deaths due to workplace risks,
      and calls for action. OBJECTIVES: Global burden estimates and counts of deaths
      assist ministers and other decision and policy makers to make informed decisions
      and to take action regarding risk reduction. METHODS: The WHO CRA methodology
      combined the proportions of the population exposed to five occupational hazards
      (excluding numerous risks due to inadequate global data) with relative risk
      measures to estimate attributable fractions of the selected health outcomes for
      both morbidity and mortality. ILO estimates of total numbers of global work
      related injury deaths apply national fatality rates to employment data for the
      particular country; for disease deaths ILO uses an attributable risk approach.
      RESULTS: In 2000, the selected occupational risk factors were responsible
      worldwide for 37% of back pain, 16% of hearing loss, 13% of chronic obstructive
      pulmonary disease (COPD), 11% of asthma, 8% of injuries, 9% of lung cancer and 2%
      of leukemia, and about 100% of pneumoconioses and mesothelioma. These selected
      risks at work resulted in the loss of about 24 million years of healthy life and
      caused 850,000 deaths worldwide, about 40% of the ILO estimate of 2.2 million
      total deaths. CONCLUSIONS: These global and regional analyses have identified
      areas where specific preventive actions are required.

PMID- 17017365
TI  - Toxicogenomics and environmental diseases: the search for biomarkers predictive
      of adverse effects.

PMID- 17017366
TI  - Guidance values for the biomonitoring of occupational exposure. State of the art.
AB  - Biomonitoring was developed for the assessment of the health risks from exposure
      to chemicals at work, and the approaches and concepts of biomonitoring are
      derived from such exposures. At present, biomonitoring is increasingly used also
      to assess exposure from the environment. Biomonitoring and assessment of external
      exposure are complementing activities, where the exposure assessments are much
      more widely applied, especially when the number of chemicals concerned is
      considered; environmental analysis also offers the distinct advantage of
      speciation analysis--which is very poorly developed for biomonitoring.
      Biomonitoring on the other hand provides information on exposure from all
      sources, and via all absorption routes, and considers also accumulation of the
      chemical in the body. Bio monitoring using exposure biomarkers thus consider
      interindividual differences in the absorption, while use of effec biomarkers
      ideally also considers interindividual differences in sensitivity. Few effect
      biomarkers, however, have been validated. The major challenges of biomonitoring
      are the development of monitoring methods, which are inexpensive enough to be
      applied at a frequency that makes possible meaningful biomonitoring of chemicals
      with a short half-time; development of exposure biomarker guidance values
      specific to individual species of different metals; ex pansion of the repertoire
      of validated effect biomarkers; and validation and application to effect
      monitoring of the omic technologies. Another major challenge is a reconsideration
      of the basis of biomonitoring action limits to reflec the change in the work
      place: Biomonitoring should be adapted to assist in the generation of a healthy
      workplace which is capable of attracting workers, and assist them to perform
      their work effectively--rather than just to guarantee absence of serious health
      effects.

PMID- 17017367
TI  - Behavioral toxicology: from historical background to future trends.
AB  - In the 1960's and 70's some investigators started to use behavioral tests in
      toxicology, realizing that classical toxicological methods were inadequate to
      describe the negative effects on workers health caused by workplace neurotoxic
      exposures. Among the first publications were those of Helena Hanninen, who
      reported on exposure to CS2 (24, 22). In clinical examinations, these workers
      presented severe functional changes to the central nervous system (CNS), although
      there were no observable signs of frank brain damage. In experimental studies of
      effects from acute exposures to various chemicals, methods from classical
      toxicology were definitely not useful. Such investigations were performed with
      exposure to carbon monoxide and to different solvents. Studies were carried out
      in the US, Sweden, and Germany, and reported by Richard Stewart (53), Francesco
      Gamberale (15, 16), and Gerhard Winneke (63). Rapid development followed.
      Scientists active in behavioral toxicology gathered at various meetings, and in
      1982 an international symposium dedicated solely to the use and development of
      behavioral testing techniques in toxicology was organized by Renato Gilioli. He
      then used the Scientific Committee of Neurotoxicology and Psychophysiology of the
      International Commission on Occupational Health as a platform for a series of
      triennal symposia. The 9th meeting was held in Korea 2005, and the 10th will be
      organized in Costa Rica 2008. By providing a basis for the exchange of scientific
      knowledge and ideas, these symposia have been successful in further advancing the
      development and application of behavioral techniques in toxicology. This history
      is presented in some more detail, and a few possibilities for further development
      of the area will be discussed.

PMID- 17017368
TI  - Framework for considering genetics in the workplace.
AB  - There has been aproliferation of genetic information in the last 25 years
      resulting in a spectrum of existing and potential uses in the workplace. These
      uses of have different issues and implications which may be more clearly
      considered in a framework that identifies three distinct uses (research,
      practice, and regulation/litigation) for inherited genetic factors and acquired
      genetic effects. Inherited genetic factors pertain to the characteristics of the
      genes, and acquired genetic effects to the impact on genes and chromosomes of
      environmental and constitutional factors. Critical in assessing the issues
      involving genetics in the workplace is attention on the rights of workers,
      validity and clinical utility of genetic information, cost pressures on
      employers, and societal implications. Genetic information may provide mechanistic
      and diagnostic insight into occupational diseases and allow for targeting high
      risk groups, improving risk assessments, and providing early indicators of risk.
      However, these benefits are more likely to be realized and problems avoided when
      the different uses are considered in a framework that distinguishes them by type
      and content. The application of such a framework makes it easier to assess
      whether there is a sufficient evidence base and worker safeguards in place for
      any particular use of genetic information.

PMID- 17017369
TI  - A harmonised approach to setting OEL's.

PMID- 17017370
TI  - Occupational hygiene: where from and to?
AB  - Occupational Hygiene was born in the forties in the USA, from the need to focus
      on the causes of the occupational diseases from a scientific and technical point
      of view. In other words this is to understand how to detect, how to evaluate and
      how to control the chronic risks at the workplace. The discipline developed very
      well from that time up to the nineties thank to a strong commitment of dedicated
      people and professional societies supported by international organizations such
      as the ILO and the WHO. Nowadays the situation of Occupational Hygiene differs
      considerably between countries which can arbitrarily be categorized according to
      the "culture and tradition" they have in this field. The development of this
      science has decreased in the countries where it has been very well established.
      This is probably due to the fact that the field of Occupational Health has been
      enlarged very much in the last decade so that Occupational Hygiene has to
      struggle more than before to defend its ecological niche (specificity) in this
      vast domain. In some countries the discipline is mixed with safety or
      environmental protection or even with the quality management and there is no
      curricula for Occupational Hygiene only. In many countries it simply does not
      exist. What will be the future of Occupational Hygiene? It is not possible to
      answer this question but there are clear opportunities to show the importance of
      Occupational Hygiene such as the REACH regulation in Europe which full comply
      with the core competencies of this profession. Other opportunities such as the
      elaboration of simple tools to assess and control the occupational hazards
      (toolkits) may also lead to a decrease in the need of well educated professionals
      since these tools will not require a long training to be used. In conclusion, the
      future will depend on the way the actual occupational hygienists will work to
      become more visible and to be considered as essential partners to reach the main
      goal of Occupational Health which is to build up healthy workplaces, for healthy
      companies in a healthy economy. The Occupational Hygiene Societies at the
      national level and the IOHA (International Occupational Hygiene Association) at
      the international level, will have a key role to play in this future evolution.

PMID- 17017371
TI  - Low-dose occupational exposure to asbestos and lung cancer risk.

PMID- 17017372
TI  - CASH--an innovative approach to sustainable OSH improvement at workplace.
AB  - Occupational health department of a large private enterprise located in India
      launched Project CASH--Change Agents for Safety and Health, at manufacturing
      units of the enterprise to bring about a positive change in work environment and
      improvement in work practices to reduce occupational health risk.
      Multidisciplinary teams of change agents were constituted and were given
      intensive training inputs. Reduction in exposure to noise, dust and heat stress
      were identified as specific objectives after a baseline survey of the work
      environment. Occupational safety and health knowledge and training was imparted
      to all field personnel to improve their work practices and attitudes. The focus
      of the actions was on engineering control measures and process engineering
      changes necessary for workplace improvement. Noise levels were reduced by an
      average of more than 9dBA in most of the top ten high noise locations. Out of two
      locations identified for dust exposure, one was fully eliminated and dust levels
      at other location were significantly reduced. Heat stress was reduced in all
      three identified locations with an average reduction of more than 3 degrees C in
      WBGT levels. Thus, final evaluation of workplace environments revealed
      significant reduction in exposure to all identified agents, viz noise, dust and
      heat fulfilling the project objectives. Educating and empowering the team led to
      reduction of occupational health risks in the work environment. There was
      positive attitudinal and behavioural change in safety and occupational health
      awareness & practices among employees. The monetary savings resulting from
      improvements far outweighed the investments. Success of this pilot project was
      followed up with further similar projects and their number has grown in geometric
      proportion for the last three years indicating the sustainability of the project.

PMID- 17017373
TI  - Lessons from SARS in an age of emerging infections.
AB  - SARS, the first pandemic of this century, commanded the world's attention and
      required public health actions at the national and international levels. In an
      age of emerging infections, the lessons learnt from combating SARS can be used to
      improve our preparedness capabilities in three key areas to effectively tackle a
      public health emergency of international concern. The first area is in outbreak
      alert, which encompasses use of surveillance to detect, assess, notify and report
      events involving death or disease, and share information widely to enable proper
      risk assessment. The system must able to build up a comprehensive picture with
      appropriate warning for zoonotic diseases, environmental health and food safety.
      The second area is in public health response. In the event of an outbreak alert,
      the authorities must be able to quickly investigate cases/deaths and institute
      comprehensive control measures to break the chain of transmission. Protection of
      healthcare workers and reducing the opportunities for spread of infection through
      contact tracing and quarantine are important. The third area is in international
      health. This comprises health requirements for inbound and outbound travellers at
      the border checkpoints and global information exchange to mitigate the risks of
      travel abroad. Extrapolating these lessons to a wider public health context, our
      rapidly changing global infectious diseases situation mandates that we evaluate
      all available public health tools and build institutional capacity to effectively
      manage emerging infections.

PMID- 17017374
TI  - Is globalisation outpacing ethics and social responsibility in occupational
      health?
AB  - INTRODUCTION: The definition of globalisation is varied. However, one certainty
      is that in a globalised world the borders are porous in many aspects; people
      movement, goods exchange, knowledge sharing and redistribution of labour. The
      concept of globalisation, its impact on society, and its direction leads to a two
      sided argument. Could this be the effect of globalisation on ethics and social
      responsibility, as it is perceived? This paper endeavours to further our
      understanding of the dynamic relationship of globalisation, ethics and social
      responsibility in occupational health. METHOD: The multidisciplinary activity
      approach to occupational health was used. The globalisation, ethical and social
      responsibility relationship of the activities in occupational health was analysed
      using a schematic map of the direct and indirect influences. RESULTS: The
      analysis revealed areas that can be clustered to address the interaction between
      driving forces in occupational health ethics and social responsibility for a
      healthy workforce. DISCUSSION: Each cluster is discussed highlighting areas of
      concern. In the discussion proposals are made on how we can modify the way we
      think in order to avoid repeating mistakes. Suggestion is made of using an
      innovative method borrowed from other disciplines and adopted for use in
      occupational health. A partnership approach is proposed and explored on how it
      will be applied in situations of unequal balance of power.

PMID- 17017375
TI  - The scientific basis of a total asbestos ban.
AB  - Worldwide, in the new millennium, standards for the protection of workers and the
      general population from as-bestos risks are not equally stringent in all
      countries. The present review analyzes some arguments which in recent years have
      been proposed as a rationale for the reconsideration of the scientific background
      of a total asbestos ban, such as that adopted in the European Union. The
      conclusion is that in order to ensure adequate protection, there is no
      alternative to a total ban. The evidence for carcinogenicity of chrysotile is as
      good as for the amphiboles, the carcinogenic potency of chrysotile is lower than
      that of the amphiboles, but risk estimates must also be based on extent of
      exposure (nowadays chrysotile represents 95% of asbestos used worldwide). The
      fact that induction of mesothelioma by asbestos results from the interaction of
      environmental exposure and genetic factors reflects a general phenomenon in
      carcinogenesis and does not warrant any re-consideration of the role of asbestos.
      The role of SV40 as yet is unclear: even assuming that current risk estimates are
      correct (which is debatable), this agent would interact with asbestos in only a
      faction of mesothelioma cases. The effectiveness of protocols suggested for
      "controlled use" has not been tested with a scientfiic approach: they seem hardly
      practicable, particularly in the countries which are currently the major
      consumers of asbestos.

PMID- 17017376
TI  - From clinical activities to didactics and research in occupational medicine.
AB  - BACKGROUND: The daily practice of Occupational Physicians in the mot
      industrialized countries suggests that the frequency of traditional occupational
      diseases is progressively lowering, their gravity is decreasing, and the
      etiological factors are changing. This trend should be quantitatively and
      qualitatively verified with ad hoc studies. The information is particularly
      relevant for Academic Institutions where medical students and residents in
      occupational medicine are trained. OBJECTIVES: To analyse the trends of clinical
      diagnoses and health surveillance activities conducted in the last 15 years by an
      Italian Institute of Occupational Health, and to gain information on the most
      relevant topics to be taught in academic program and to be addressed with future
      research. METHODS: Data sources were represented by the computerised registration
      of a) diagnostic activities and b) health surveillance programs, conducted by the
      Institute of Occupational Medicine of the University of Brescia, a highly
      industrialized area in Northern Italy. The observation period was from 1990 to
      2005. The health surveillance programs regarded workers pulled from an iron
      foundry, a veterinary institute, a health departments for the assistance of
      elderly subjects, a nursery schools and a municipal department for road
      maintenance. RESULTS: Diagnostic activities were conducted on 9080 subjects, who
      had been referred for suspected occupational disease. The diagnosis of
      occupational disease was confirmed for 3759 cases. Multiple diseases were
      diagnosed in 1554 subjects, yielding the total number of 5721 occupational
      diseases. The most frequent diagnoses accounted for allergic skin disease
      (23.4%), followed by pneumoconiosis (20.4%), chronic obstructive pulmonary
      disease (15.9%), noise hearing loss (7.1%), musculoskeletal disorders (6.9%),
      respiratory allergies (6.9%), cancer (5.9%), miscellaneous (6.4%). When limited
      to the last quinquennium, the analysis showed a definite increase of
      muskuloskeltal disorders, cancer, and, although at a lesser extent, diseases due
      to psychosocial factors. The analysis of the health surveillance programs
      regarded 1207 workers, and showed that various non occupational diseases caused
      limitation to individual work fitness. The most frequent conditions were
      musculoskeletal disorders (65%) and skin diseases (14%). CONCLUSIONS: The results
      from these two investigations are important not only for the didactic program run
      by the Institute, but also because they indicate the most relevant topics to be
      addressed with future research, at least at a local level.

PMID- 17017377
TI  - Occupational asthma.
AB  - Occupational asthma (OA) is one of the most common forms of occupational lung
      disease in many industrialized countries, having been implicated in 9 to 15% of
      adult-onset asthma. Work-related asthma includes: 1. immunologic OA,
      characterized by a latency period before the onset of symptoms; 2. nonimmunologic
      OA, which occurs after single or multiple exposures to high concentrations of
      irritants; 3. work-aggravated asthma, which is pre-existing or concurrent asthma
      exacerbated by workplace exposures; and 4. variant syndromes. OA is important to
      recognize clinically, because it has serious medical and socioeconomic
      consequences. Diagnosis of OA should be confirmed by objective testing early
      after its onset. Removal of the worker from exposure to the causal agent and
      early treatment with anti-inflammatory drugs lead to a better outcome. Assessment
      of the work environment and identification of host factors may provide us with
      useful information about the mechanisms involved in OA. Another issue concerns
      strategies for preventing OA which should be implemented.

PMID- 17017378
TI  - Indoor air quality and health in offices and other non-industrial working
      environments.
AB  - BACKGROUND: Over the last 30 years, transformation of indoor environments--in
      particular in office blocks--has been associated with complaints from workers of
      discomfort, malaise and even diseases termed Building Related Illnesses (BRI)
      which are classified as specific (e.g. Legionnaire disease, asthma,
      hypersensitivity pneumonia) or non-specific (e.g. the Sick Building Syndrome).
      METHODS: A review was made of data from international public health
      organisations, epidemiological, clinical and experimental studies and congress
      proceedings from 1990 to 2006 on the topic of indoor air quality and health in
      modern, non-industrial workplaces. RESULTS: Studies focused on ventilation,
      temperature and air humidity and specific pollutants such as Volatile Organic
      Compounds, particules asbestos fibres, environmental tobacco smoke, radon and
      biological agents. We can now measure microclimate parameters and many indoor air
      pollutant levels as well as their effects on health; we can also formulate
      indications of threshold and guideline values for some of these and make a
      preventive assessment for toxic emissions from construction and furnishing
      materials. A stepwise, multi-disciplinary approach--with the specialist in
      occupational medicine playing a major role--is most suitable for dealing with BRI
      and the effects of poor indoor air quality on health. CONCLUSIONS: Better
      criteria are needed to study emission of substances into the indoor environment,
      adequacy of ventilation, additive or synergistic effects of mixtures of chemicals
      and toxicity of micro-organism decomposition products. Objective clinical tests
      to assess the effects of indoor pollutants on health and indices for Indoor
      Environmental Quality in assessing buildings need to be improved.

PMID- 17017379
TI  - The emerging infectious disease.

PMID- 17017380
TI  - Occupational health and safety in agriculture: situation and priorities at the
      beginning of the third millennium.
AB  - Agriculture is a human activity, which includes a number of different tasks and
      occupies a huge number of people worldwide. Estimates of World Bank for 2003
      suggest that 51% of globalpopulation lives in rural areas. ILO estimates that 1.3
      billion of workers are engaged in agriculture, and they represent almost a half
      of the total number of economically active subjects (2,838,897,404). In developed
      countries, agriculture workers are only a small fraction of the whole work force
      (up to 9% according to ILO data), while in developing countries, especially in
      Asia, agriculture workers represent up to the 60% of the total work force. Most
      agriculture workers reside in Asia, in the Pacific (74%) and in Africa (16%). ILO
      estimates suggest that half of fatal occupational injuries in the world are
      attributable to agriculture. This means that around 170,000 agriculture workers
      die every year as a consequence of occupational injuries. Using the same
      estimate, half of the fatal accidents could be linked to agricultural activities
      (more than 130 million). Comparing this estimate with the 6.328.217 people
      injured in war in 2002 or with the 20-50 million injured victims of road
      accidents, one has a much clearer picture about the importance of preventing
      agricultural injuries. In a complicated situation such as occupational health and
      safety problems in agriculture, it is not so easy to select priorities clearly.
      But "legalization" of agriculture workers could be a key to solving all the other
      problems. Actual data on fatal and non-fatal occupational injuries in agriculture
      show that occupational health and safety issues are among the top priorities for
      that discipline.

PMID- 17017381
TI  - Risk assessment and management of occupational exposure to pesticides in
      agriculture.
AB  - Nearly 50% of the world labour force is employed in agriculture. Over the last 50
      years, agriculture has deeply changed with a massive utilisation of pesticides
      and fertilisers to enhance crop protection and production, food quality and food
      preservation. Pesticides are also increasingly employed for public health
      purposes and for domestic use. Pesticide are unique chemicals as they are
      intrinsically toxic for several biological targets, are deliberately spread into
      the environment, and their toxicity has a limited species selectivity. Pesticide
      toxicity depends on the compound family and is generally greater for the older
      compounds; in humans, they are responsible for acute poisonings as well as for
      long term health effects, including cancer and adverse effects on reproduction.
      Due to their intrinsic toxicity, in most countries a specific and complex
      legislation prescribes a thorough risk assessment process for pesticides prior to
      their entrance to the market (pre-marketing risk assessment). The post-marketing
      risk assessment takes place during the use of pesticides and aims at assessing
      the risk for exposed operators. The results of the risk assessment are the base
      for the health surveillance of exposed workers. Occupational exposure to
      pesticides in agriculture concerns product distributors, mixers and loaders,
      applicators, bystanders, and rural workers re-entering the fields shortly after
      treatment. Assessing and managing the occupational health risks posed by the use
      of pesticides in agriculture is a complex but essential task for occupational
      health specialists and toxicologists. In spite of the economic and social
      importance of agriculture, the health protection of agricultural workforce has
      been overlooked for too many years, causing an heavy tribute paid in terms of
      avoidable diseases, human sufferance, and economic losses. Particularly in the
      developing countries, where agricultural work is one of the predominant job, a
      sustainable model of development calls for more attention to occupational risks
      in agriculture. The experience of many countries has shown that prevention of
      health risk caused by pesticides is technically feasible and economically
      rewarding for the individuals and the whole community. A proper risk assessment
      and management of pesticide use is an essential component of this preventative

PMID- 17017382
TI  - The occupational physician in the post-modern world.

PMID- 17017383
TI  - [Occupational cancer. The role of the occupational physician in systematic search
      and aetiological diagnosis of lung cancer. Analysis of a case list].
AB  - BACKGROUND: About 15% of lung cancers (LC) might be attributable to occupation.
      However, clinical practice shows that LC percentage for which occupational
      aetiology is recognized is lower than expected. OBJECTIVES: To address the role
      of Occupational Physicians (OP) in systematic search and aetiological diagnosis
      of LC. METHODS: The search was carried out at a university hospital in Brescia,
      northern Italy, a highly industrialized area with many workers potentially
      exposed to occupational lung carcinogens. Through short occupational history
      forms, physicians of various departments refer all new cases of primary LC to OP
      When occupational exposure to lung carcinogens is presumed, the OP evaluates the
      case at the occupational health clinic and sends clinical reports to notifying
      physicians, containing aetiological diagnosis and indications for medico-legal
      obligations. RESULTS: Before 1998, few cases were referred to the OP and even
      less were compensated. The search yielded 1502 LC; after screening, full
      occupational health evaluation was performed in 693 cases: occupational aetiology
      was recognized in 182 (26%). Risk factors were silica, asbestos, polycyclic
      aromatic hydrocarbons, truck driving, painting, road paving; many workers were
      exposed to multiple carcinogens. 48 cases were compensated, many others are under
      litigation. CONCLUSIONS: A systematic LC search made it possible to: reach an
      aetiological diagnosis and reduce the gap between expected LC and those
      reported/compensated; inform health authorities and undertake preventive action
      in workplaces; detect sentinel events; provide epidemiological data at community
      level; promote cooperation among health professionals (oncologists, surgeons,
      pneumologists, general practitioners, plant OP); increase teaching opportunities
      for medical students, those taking a specialisation course in occupational
      health; provide counselling and expert opinions for individual subjects, trade
      unions, employers, law courts.

PMID- 17017384
TI  - [Lung cancer in a female non-smoker with occupational exposure to asbestos: a
      case report].
AB  - BACKGROUND: Until recently, asbestos was widely used in a variety of industrial
      processes. Workers exposed to asbestos may develop lung and pleural diseases such
      as asbestosis, lung cancer, benign pleural effusion, pleural plaques and
      mesothelioma. OBJECTIVE: To describe a clinical case of lung cancer in a female
      non-smoker with occupational exposure to asbestos. METHODS: The clinical and
      occupational history was based on the information kindly provided by the
      Occupational Unit of the National Health Service and on the case history of a
      hospital admittance in 2001, when the patient underwent surgery for lung cancer.
      RESULTS: The patient worked for 6 years in an asbestos manufacturing industry
      where she was exposed to high concentrations of asbestos, and then worked for 14
      years in a sugar refinery only during the summer. She had benign pleural
      effusion, pleural plaques, asbestosis and lung cancer. CONCLUSIONS: We concluded
      that a six-year exposure to high doses of asbestos may induce lung cancer and
      asbestosis in a female non-smoker.

PMID- 17017386
TI  - [Berylliosis in Italy: a case of "sarcoidosis" under the threshold limit value].
AB  - BACKGROUND: Berylliosis is caused by a chronic immune reaction to beryllium; in
      Italy the first case of beryllium exposure-related disease was described in 1935
      by Fabroni-Marradi and two additional cases of beryllium disease were
      subsequently described by Ambrosi and co-workers in 1968. No case has since been
      recognized using the standardized criteria including immunological testing.
      OBJECTIVES: To describe a case report of clinically significant berylliosis that
      occurred in a man exposed to beryllium for ten years in the workplace at
      concentrations below the permitted threshold limit value. METHODS: The man
      complained of dyspnoea, dry cough, weakness and weight loss for the past year and
      was at first diagnosed as suffering from sarcoidosis because of increased
      angiotensin converting enzyme levels, alteration of hepatic and renal functional
      indexes, the presence of diffused reticulo-nodular lung abnormalities with high
      resolution computed tomography that also showed enlarged mediastinal lymph nodes,
      abnormal lung physiology with reduced diffusion capacity and a bronchial biopsy
      showing granulomatous lesions. Because of the occupational history immunological
      testing and high resolution HLA class II typing were performed. RESULTS: The high
      response to beryllium in the lymphocytes proliferation test and the HLA typing
      which revealed the presence of the two susceptibility markers HLA-DPGlu69 and HLA
      DRPhe47 led to a diagnosis of berylliosis. CONCLUSIONS: The importance is
      stressed of suspecting a diagnosis of berylliosis in the proper occupational
      contexts and encouraging the use of immunological tests for diagnosis, and also
      the need for critical revision of the permitted threshold limit values.

PMID- 17017385
TI  - [A particular case of hard metal disease].
AB  - BACKGROUND: The production and the use of hard metal tools have becoming
      increasingly widespread since the second half of the last century also thanks to
      the great variety of applications that extends from DIY to the aeronautical
      industry. It has already been known for many years that occupational exposure to
      hard metals dusts (which occurs especially in people employed in production of
      the metals or in the sharpening of tools that contain them) can determine the
      onset of pulmonary fibrosis, bronchial asthma and contact dermatitis. OBJECTIVES:
      clinical evaluation of a peculiar case of hard metal disease. Descriptions of
      cases with single pathological pictures due to hard metals, are, in fact, common
      in the literature, neither are cases with two different clinical pictures (more
      frequently asthma and pulmonary fibrosis) rare. However, cases in which all the
      signs and symptoms appeared simultaneously have never been reported. METHODS: a
      male worker aged 41 years, employed i a hard metal factory for seven years in
      sintering, and then in grinding. A year later he developed dry cough, wheeze, and
      eczematous patches. The diagnosis of hard metal disease was based on the work
      related symptoms, clinical evaluation, spirometry, chest x-ray, HRCT and patch
      tests. RESULTS: during the working period, ventilatory function decreased
      substantially, and then normalized one month after the patient stopped working.
      Patch tests confirmed sensitivity to cobalt, and skin lesions improved, as did
      ventilatory function. Chest x-ray and HRCT showed a pulmonary fibrosis that, at
      the last radiological examination, was still unchanged. CONCLUSIONS: The
      particular susceptibility to the development of the diseases, could, in our
      opinion, be in relationship with the race of the subject, many studies
      (particularly American) have shown that allergic diseases are more frequent, and
      often more serious, in African subjects, particularly in immigrants from Africa.
      In the case of occupational diseases attention also needs to be given to the fact
      that immigrants are often employed in duties that involve a greater exposure to
      harmful or sensitizing agents. The occurrence of a whole series of occupational
      allergic diseases among these workers is therefore to be expected.

PMID- 17017387
TI  - [Implementation and application of an index method for assessment of occupational
      biological risk in a hospital setting].
AB  - BACKGROUND: Over the last years several mathematical methods have been proposed
      by The Italian Society for Occupational Health and Industrial Hygiene (SIMLII)
      with the aim of assessing exposure to occupational risks. The current way of
      assessing biological risk is based on the widely used but poorly accurate formula
      R = P x D. Use of more complex methods of assessment of exposure involves many
      problems due to: complexity and poor standardisation of micro-organisms
      concentration, ubiquitary diffusion of biological agents in the working
      environment, lack of dose-response curves, uncertainty about the existence of an
      effective infection threshold for many micro-organisms, etc. OBJECTIVES: In order
      to assess occupational exposure to biological risk in health care settings an
      index method was developed according to the Guidelines for health surveillance of
      health care workers drawn up by SIMLII. METHODS: A check-list containing the
      features of the two main modes of transmission of infectious diseases (blood
      borne and air-borne) was applied to the wards of Cuneo Hospital. The selected
      variables were combined, according to the different transmission modalities, into
      two mathematical models producing, for each of them, a numeric value of the
      degree of the risk. RESULTS AND CONCLUSIONS: The cut-off values chosen to
      separate both the final degrees of exposure by blood-borne (mild, medium and
      high) or by air-borne transmission (very low, very limited, limited, medium) were
      statistically different (P < 0.001). The most important determinants of the
      differences found in the comparison between different exposure levels were:
      frequency of work manoeuvres at high risk of exposure and/or frequency of
      performance, building deficiencies, extent of application of the work and
      behaviour procedures, degree of training, number of occupational injuries, the
      occupation of physician, and, for the nursing category, duty in a medical ward.
      This index method seems to assure better results, both in terms of efficacy and
      appropriateness, compared to the methods previously used to assess biological
      exposure. The results justify the need for further investigation.

PMID- 17017388
TI  - [Medical legal aspects of the requirement to report noise-induced hearing loss
      notified to INAIL to the judicial authorities].
AB  - BACKGROUND: Law 689/81 redefined how personal lesions could be prosecuted by
      means of explicit mention of occupational diseases among the type of offences
      subject to mandatory reporting. The high prevalence of noise-induced hearing loss
      (NIHL) among occupational diseases has monopolized attention towards
      identification of a method that can define the penal limits of this occupational
      disease; however, up to now no single univocal approach exists. For this reason
      operators in this field are perplexed as to the requirement of reporting judicial
      authorities (J.A.). On the other hand, the great changes that have occurred in
      compensation of occupational diseases by INAIL (sentence 179/88 of the
      Constitutional Court) and the evaluation of the same in terms of biological
      impairment (Law D.Lgs. 38/00 and Law D.M. 12.7.00) have led to an ample and
      accurately assessed protection against, work-related hearing loss. OBJECTIVES AND
      METHODS: From this perspective the authors analysed 52 cases of NIHL reported to
      INAIL. They compared the assessments made according to Law D.M. 12.7.00 and the
      guidelines for reporting to the J.A. according to four different methods
      generally used in the criminal field: Benciolini, Merluzzi, SIMLII guide lines
      and SIO guidelines. By stressing the need for a preliminary qualitative
      evaluation of NIHL in the penal report, the authors. restricted the analysis to
      the quantitative aspect with technically compatible graphs. RESULTS: Processing
      the data resulting from application of the different methods, led to the
      assumption that audiometric graphs that showed a percentage of biological
      impairment according to Law D.M. 12.7.00 higher than 2.40% must always be
      reported to the JA. For audiometric graphs that show impairment of less than 0.5%
      recommendations to report tare rather sporadic. For the graphs with intermediate
      values recommendations to report to the J.A, which are always present in at least
      one of the methods, are not constant, and in particular there is no linear
      correlation between the percent grading of biological impairment and the
      recommendation to report; this is probably due to a difference in concept of the
      various methods which reflects on the respective scale of values. CONCLUSIONS: On
      the basis of these results the authors suggest that reporting to the judicial
      authority can be recommended for all those cases whose quantification, according
      Marello's schedule, is higher than 0.5%, as these cases can, according to the
      penal code, supplement assessment of impairment.

PMID- 17017389
TI  - [Consensus document on multiple chemical sensitivity (MCS)].

PMID- 17017390
TI  - [Occupational tumor research and use of the hospital discharge file: comments on
      the usefulness of the utilization of administration data for research of clinical
      cases, experience with OCCAM].

PMID- 17017391
TI  - [An emerging problem: which theoretical reference values should be used for
      immigrant workers?].

PMID- 17017392
TI  - [Note of the Labor Ministry on the substitution of the competent physician].

PMID- 17017393
TI  - [Work of the parliamentary research commission on the phenomenon of occupational
      injuries particularly regarding the so-called "white death"].

PMID- 17017394
TI  - Value of CK14 and CD56 immunostaining in distinguishing small cell carcinoma from
      squamous cell carcinoma of the esophagus.
AB  - Primary small cell carcinoma of esophagus (SCC) is a rare disease but has more
      aggressive behavior than esophageal squamous cell carcinoma (SQC). The
      distinction of SCC from SQC is very important therapeutically. Few systematic
      studies of immunohistochemical analysis to differentiate primary esophageal SCC
      with concomitant SQC, and adjacent normal esophageal epithelium have been
      reported. The objective of this study is to know the immunohistochemical markers
      in distinguishing SCC from SQC of esophagus. We studied 6 cases of primary
      esophageal SCC histologically and immunohistochemically using 15 different
      antibodies including a cytokeratin (CK) panel and neuroendocrine markers. Pure
      SCCs were identified in 2 of the 6 cases (33.3%), and the remaining 4 cases
      (66.7%) were found to exhibit combined SCC with an SQC component. Among the
      combined types, in situ SQC was observed in all 4 cases (100.0%) and invasive SQC
      was observed in 3 cases (75.0%). Among the normal esophageal epithelia specimens
      (n=7), CK14 expression was seen 6 out of 7 (85.7%) specimens and CKAE1/3 in 5 out
      of 7 (71.4%) specimens. CD56 was more frequently expressed among the SCC
      specimens (4/6; 66.7%) than among the SQC specimens (0/4; 0%; p = 0.07). The
      expression of p53 protein in SCC (4/6; 66.7%) and SQC (3/4; 75.0%) specimens was
      significantly more frequent than in normal esophageal epithelium (0/7; 0%; p =
      0.02 each). Neurone-specific enolase (NSE), synaptophysin, and CKAE1/3 were
      expressed in 83.3%, 66.7%, and 66.7% of the SCC cases (n=6), respectively. NSE
      expression was significantly more frequent in SCC specimens (5/6; 83.3%) (p =
      0.02) than in normal esophageal epithelium (0/7; 0%; p = 0.02). However, the
      frequencies of NSE expression in SCC (5/6; 83.3%) and SQC (2/4; 50%) were not
      significantly different. All of the SQC specimens (n=4) expressed CK14 and
      CKAE1/3. The CK14 expression was significantly more frequent in SQC specimens
      (4/4; 100.0%) than in (p = 0.04) SCC specimens (1/6; 16.6%; p = 0.04). These
      findings suggest that the CK14 and CD56 may be useful markers for differentiating
      SQC from SCC and vice versa. The p53 may also be useful to differentiate normal
      esophageal epithelium from SCC or SQC tissue.

PMID- 17017395
TI  - Excessive intrastent plaque volume is the major cause of restenosis after
      intracoronary bare metal stent implantation: a 3-dimensional intravascular
      ultrasound and quantitative coronary angiography based study.
AB  - Vascular response after percutaneous coronary intervention (PCI) may differ in
      different ethnic group. Here we show the impact of peri-stent and intra-stent
      remodeling on coronary stenotic lesions in a group of Japanese patients. Those
      lesions were evaluated before, after and during follow up, with 3 dimensional
      intravascular ultrasound (IVUS) (3-D IVUS) and quantitative coronary angiography
      (QCA) 30 patients with pre, post and follow up IVUS were enrolled. Quantitative
      data are presented as the mean +/- SD, and categorical data as frequencies.
      Binary variables were compared with Mann Whitney's U test. There were 7 cases
      with restenosis (RS) and 23 cases with no-restenosis (NR). In QCA based
      evaluation, minimum lumen diameter (1.2 +/- 0.4 mm vs. 2.4 +/- 0.6 mm, p < 0.001)
      and % diameter stenosis (59.1+/- 16.1 vs. 23.3 +/- 16.1, p < 0.001) were
      significantly reduced in RS at follow up. Acute gain was similar among both
      groups (RS; 2.1 +/- 0.6 mm vs. NS; 2.2 +/- 0.7 mm, p = 0.5), however, late loss
      was significantly increased in RS (2.1 +/- 0.8 vs. 0.8 +/- 0.5, p < 0.001). At 3
      D IVUS based follow up, lumen volume index was significantly reduced in RS (3.6
      +/- 0.8 mm3/mm vs. 6.9 +/- 0.8 mm3/mm, p < 0.01). There was higher intrastent
      plaque volume index in RS in comparison to NR (5.4 +/- 1.4 mm3/mm vs. 3.1+/- 1.1
      mm3/mm, p < 0.05). Linear regression analysis showed a tendency for a significant
      inverse correlation between the percentage of delta peristent volume index and
      the percentage of delta intrastent volume index (R2 = 0.12, p = 0.054). The
      intrastent plaque growth is the major player in causing restenosis.

PMID- 17017396
TI  - Osteoarthritic femoral articular cartilage of knee joint in man.
AB  - Osteoarthritis is the most common of the various articular disorders affecting
      man. The present study was conducted to observe the microstructure of
      osteoarthritic human femoral articular cartilage by light microscopy. Fifteen
      osteoarthritic cartilage specimens obtained from patients with primary
      osteoarthritis (52-80 years) undergoing total knee replacement were processed for
      paraffin sections. 5 m thick sections were observed under light microscope. The
      articular surface appeared to be very irregular and fibrillated in all the
      specimens. The cartilage did not show the normal zonation. Various changes seen
      were different in all specimens and they were not related to age. Most common
      feature of the osteoarthritic articular cartilage was the presence of large
      clusters of cells in 60.0% specimens. Detached parts of the degenerating
      cartilage were present in the joint cavity in the form of loose bodies. The
      collagen fibres appeared to be coarser and irregular even near the non
      fibrillated areas. Numerous tangential, oblique and vertical splits were also
      observed. Osteoblastic and osteoclastic activity was seen in the subchondral bone
      and the osteolytic cyst appeared to invade the cartilage from the subchondral
      bone. Blood vessels from the subchondral bone were also seen invading the
      cartilage in 20.0% specimens. The various changes seen in the osteoarthritic
      cartilage could be an effort of cartilage repair but such attempts are severely
      counteracted by the osteoarthritic wear process.

PMID- 17017397
TI  - Knowledge attitude and practice (KAP) study regarding facts for life.
AB  - This knowledge attitude and practice (KAP) study was done in the married women of
      age 18-38 years in Jorpati and Gokarna village development committees of Katmandu
      district to evaluate the knowledge of "Facts for Life". There were 510 married
      women involved in this study. Altogether 28 questions were asked to each of them
      regarding the "Facts for Life". It includes the following five subjects: Safe
      motherhood, Childhood Immunization, Childhood diarrhea, Acute Respiratory
      Infection (ARI) in childhood and hygiene. There was a significant increase in
      knowledge about hygiene and knowledge regarding childhood immunization than
      diarrhea, ARI and Safe motherhood. Results showed that the overall knowledge was
      at 62.8%. This shows that still more attention is needed to Nepalese women.

PMID- 17017398
TI  - Comparative study on a homemade rapid urease test with gastric biopsy for
      diagnosis of Helicobacter pylori infection.
AB  - The main objective of this study was to determine whether a homemade rapid urease
      test was reliable when compared to histology in the diagnosis of Helicobacter
      pylori infection. Endoscopic antral biopsies from 15th August 2004 to 15th July
      2005 were studied prospectively. Rapid urease test and histological examination
      were done on all specimens. Among 160 biopsies, 56 cases showed H. pylori in
      histological section and 59 cases were rapid urease test positive. Among 56 H.
      pylori infected patients, the sensitivity, specificity, positive and negative
      predictive values, percentage of false positive, and percentage of false negative
      values of rapid urease test were 96.4%, 95.2%, 91.5%, 98.0%, 4.8% and 3.5%
      respectively. Rapid urease test is positive in significantly higher number (p <
      0.001) in histological positive cases. In conclusion our homemade rapid urease
      test is a test with good sensitivity and specificity for detection of H. pylori
      infection.

PMID- 17017399
TI  - Hormonal contraceptive like effect of estrogen in milk protein-fed male rats.
AB  - Adult male rats received daily injections (sc) of estradiol-17 beta (50
      microg/100 g body wt per day) for 7 days. When they were sacrificed 14 days after
      the last injection, serum levels of gonadotropins and testosterone and weights of
      accessory sex organs were decreased significantly, testicular 17-hydroxysteroid
      dehydroganase activity was suppressed and spermatogenesis was inhibited in 5.0%
      casein-fed estrogen-treated rats. Feeding of 20.0% casein diet to estrogen
      treated rats resulted in increased serum concentration of gonadotropins and
      testosterone. LH and testosterone appeared to be normal in 20.0% casein-fed
      estrogen-treated rats while serum FSH levels remained subnormal. The estrogen
      treated rats fed on 20.0% casein diet showed decreased spermatogenesis in
      comparison with control rats fed on 20.0% casein diet. Together, these results
      indicate that high casein diet stimulates synthesis of testicular testosterone
      and increases serum LH levels more than FSH in estrogen-treated rats. It is
      concluded that estrogen in the presence of high milk protein diet may be
      considered to be a suitable steroid hormone in the development of a male
      contraceptive.

PMID- 17017400
TI  - Antiepileptic TDM pattern at a tertiary care hospital in India.
AB  - Therapeutic drug monitoring, a comparatively new investigational procedure in
      clinical pharmacology, is considered very beneficial to epilepsy patients though
      it increase the health care cost. Aim of this study was to determine the pattern
      of use of antiepileptic drug level monitoring over the last 7 years in our
      tertiary care centre and to critically comment on its utility. Retrospective data
      audit of archived data from 1998 to 2004 and age, sex, estimated levels of
      phenytoin, carbamazepine and phenobarbitone by HPLC were noted down, tabulated
      and compared. Chi square test was used for analysis. Three thousand five jundred
      thirty four blood samples of patients requesting for 4213 estimations of
      phenytoin, phenobarbitone or carbamazepine were received. Among the obtained
      samples, 44.0% (1058) were of children, 68.0% (2402) were of males, 0.6% (22)
      patients were getting 3 and 18.0% (635) getting 2, antiepileptic medications.
      13.0% (546) samples showed level in the toxic range and 39.0% (1653) in lower
      range. There was increasing demand observed for estimation of antiepileptic
      drugs, over the 7 years. The number of abnormal values of phenytoin,
      phenobarbitone and carbamazepine did not show any significant difference over the
      years. The pattern was similar to that observed in other countries.

PMID- 17017401
TI  - Assessment of IDD problem by estimation of urinary iodine among school children.
AB  - Iodine deficiency disorder (IDD) is a major micronutrient deficiency problem in
      Nepal. Urinary iodine estimation has been the gold standard employed for the
      assessment of iodine status and of IDD. This study was conducted with objective
      to assess the urinary iodine among the school children of Kavre, Lalitpur and
      Parsa districts. Attempts were made to relate urinary iodine with salt use and
      other sociodemographic variables. Altogether 190 urine samples (74 samples from
      Kavre, 89 from Parsa and 27 from Lalitpur district) were collected from school
      children aged 5-13 years. The urinary iodine was analyzed by using urinary iodine
      assay kit (Bioclone Australia Pvt Limited). It was found that 3.2% children had
      urine iodine concentration below 20 microg/l. Similarly, the percentage of
      children with urine iodine concentration 21-50 microg/l, 51-99 microg/l, 100-299
      microg/l and above 300 microg/l were 14.2%, 10.5%, 43.7% and 28.4% respectively.
      Iodine deficient population of school children was 39.2% of Kavre, 19.1% of Parsa
      and 25.9% of Lalitpur. Overall, it was found that 27.9% children had urine iodine
      level less than the normal WHO levels. The median urine iodine level was 139.0
      microg/l of Kavre, 266.7 microg/l of Parsa and 244.4 microg/l of Lalitpur school
      children. Urinary iodine excretion (UIE) median value among male students was
      211.9 microg/l, among female students was 190.2 microg/l and the difference was
      statistically insignificant (P > 0.05). There was no significant correlation
      between consumed salt iodine level and urine iodine excretion level (P > 0.05).
      Short-term iodine supplementation programs should be arranged for iodine
      deficient children in the study districts. This study shows that IDD continues to
      be prevalent in the country as a major public health problem, which requires
      strengthening effective intervention program and other preventive measures.

PMID- 17017402
TI  - Patient's perception towards the eye health care system in a tertiary eye care
      centre in Nepal.
AB  - This study was performed to determine patient's perceptions towards eye health
      care systems in a tertiary eye care center in Nepal. Subjects were randomly
      selected from the outpatient department of Tilganga Eye Centre (TEC), a tertiary
      eye care center in Kathmandu, Nepal. The study was performed in April 2003 with
      54 patients responding to several questions concerning their satisfaction of the
      eye care process. Over 40 (74.1%) of the respondents expressed overall
      satisfaction with the service provided by the hospital staff, and 4 (7.4%) were
      not satisfied. In addition, a total of 40 (74.1%) respondents were dissatisfied
      with the extended waiting time for eye examinations and other ocular services,
      while 7 (13.0%) were satisfied. The study shows that the majority of patients who
      are treated at Tilganga Eye Centre have positive feelings about Tilganga and its
      service system. Some processes, however, could be altered or improved to augment
      the overall quality of patient care.

PMID- 17017403
TI  - Lasers in dermatology.
AB  - Laser technology, since its inception, has grown to find it's in varied fields,
      and medical science has been no exception. Dermatological surgery is in itself an
      emerging field in medical science, and the evolution of laser technology has
      further widened its scope, with various therapeutic well as diagnostic
      applications. Though the use of this technology is rapidly evolving, controlled
      studies to compare the efficacy of different types of lasers in specific skin
      conditions, or its effect on different skin types, is lacking. This study
      presents the observations of the response to the Carbon-di-oxide laser used to
      treat various skin conditions, in the Nepali skin phenotype. Lasers are being
      used to treat a wide variety of dermatological conditions, many of which did not
      have satisfactory treatment in the past. Further studies are required to study
      the effect of lasers in the Nepali skin phenotype, so as to standardize the
      wavelengths, doses and exposure times that would be suitable to treat specific
      skin conditions.

PMID- 17017404
TI  - Reverse line probe assay for the rapid detection of rifampicin resistance in
      Mycobacterium leprae.
AB  - Mutations in the rpoB gene of 40 biopsy isolates of Mycobacterium leprae were
      analyzed by reverse hybridization-based line probe assay after PCR, and nine
      distinct single-nucleotide substitutions were found. Among them, a 3-nucleotide
      substitution was found in two, and 2-nucleotide substitutions were found in seven
      isolates. This is a new finding of multiple mutations in a single point of the
      rpoB gene for rifampicin resistance. This investigation demonstrates that the
      pattern of mutations in the rpoB gene for rifampicin resistance in Nepal involves
      more variety.

PMID- 17017405
TI  - ECG findings in elderly.
AB  - There are not sufficient studies on ECG in elderly population in Nepal. This
      study attempts to evaluate the findings of ECG in elderly population in Nepal.
      ECG recordings from 171 apparently healthy geriatric subjects aged above 60 yrs
      (Mean age 70.66 +/- 7.14 yrs) from different geriatric homes were studied. The
      ECG was entirely normal in 38.6% of the study population. The major abnormalities
      were sinus bradycardia in 31 (18.1%) subjects, LVH in 25 (14.6%) subjects,
      premature supraventricular beats in 16 (9.4%) subjects, T wave changes in 11
      (6.4%) subjects and right bundle branch block 16 (9.4%) subjects. Poor R wave
      progression in precordial leads in 9 (5.3%) subjects and right atrial overload in
      4 (2.4%) were other common findings. More than one third of the elderly
      population in our study had entirely normal ECG. Majority of the abnormalities
      found in this study were very minor. These observations are important for the
      future studies evaluating healthy ageing in this region.

PMID- 17017406
TI  - Overview of cases and prevalence of jaundice in neonatal intensive care unit.
AB  - This study was undertaken to know the pattern of jaundice prevalent among the
      babies admitted at the Neonatal Intensive Care Unit (NICU) of the B. P. Koirala
      Institute of Health Sciences (BPKIHS). A total of 293 neonates including 201
      (68.6%) males and 92 (31.4%) females were admitted over a period of one year
      (15th June 2001 to 14th June 2002). Prematurity (30.0%), birth asphyxia (29.0%),
      neonatal septicemia (25.9%) and respiratory distress (23.9%) were the most common
      reasons for admission to the NICU. There were 42 cases of neonatal jaundice,
      among which babies born to primigravidae (59.5%), exceeded those born to
      multigravidae (40.5%). Pathological jaundice was found in 64.3% of the admitted
      cases of neonatal jaundice. Prematurity (33.3%) and neonatal septicemia (25.9%)
      were the most common causes of pathological jaundice, while prematurity with
      neonatal septicemia (14.8%), ABO incompatibility (11.1%), Rh incompatibility
      (7.4%) and prematurity, neonatal septicemia and ABO incompatibility combined
      (7.4%) accounted for the remaining cases of jaundice. A more detailed study
      related to the pathogenesis of jaundice among neonates is needed for the
      prevention of this disease in them.

PMID- 17017407
TI  - Easy approach to DNA shuffling: its potential implication in health sciences.
AB  - Directed evolution experiments rely on the cyclical application of mutagenesis,
      screening and amplifications in a test tube. During the laboratory evolution of
      biological molecules, recombination has been used to generate novel sequences in
      a process known as DNA shuffling. DNA shuffling is a recently developed technique
      that allows accelerated and directed protein evolution for desired properties in
      vitro, which recombines and evolves genes to rapidly obtain molecules with
      improved biological activity and fitness. DNA shuffling is generally achieved by
      DNaseI treatment and by PCR. This has led to the creation of novel proteins for a
      wide range of applications. The use of improved enzymes for medical, industrial
      and environmental purposes is prevalent today, and will be expanding. New
      applications in vaccine development and disease diagnosis are among the key
      features of DNA shuffling. However, directed evolution currently requires an
      uncertain, typically large number of labor-intensive and expensive experimental
      cycles before proteins with improved function are identified. A simplified and
      low-cost DNA shuffling protocol for random recombination of homologous genes in
      vitro is described here.

PMID- 17017408
TI  - Leprosy blindness in Nepal.
AB  - Leprosy is a systemic disease with highest incidence of ocular complications and
      one of the important causes of blindness in the world. A comparative cross
      sectional study was carried out to see the ocular involvement in leprosy leading
      to blindness in two groups of patients, one with the active disease and second
      already cured and thus released from treatment (RFT). Active cases attending
      Anandaban leprosy clinic, Patan hospital and RFT cases from Khokana leprosarium
      were included in the study consecutively. Total of 70 active cases and 101 RFT
      cases were evaluated during the study period. Active group of patients showed
      more of multibacillary type of disease than in RFT group. The prevalence of
      ocular manifestations was seen much higher among RFT cases accounting for 66.3%
      in contrast to active group where only 14.3% had ocular problems. Blindness was
      frequently seen in multibacillary (MB) leprosy patients in compare to
      paucibacillary (PB) disease in both the groups. However blindness frequency was
      seen more often among RFT cases accounting for 24% in compare to only 2.9% among
      active group. Causes of blindness were mainly corneal and cataract related
      disorders. Risk of blindness also increased with the increase in duration of
      illness. RFT group of leprosy patients are at higher risk of developing blindness
      than the active group thus eye care services should be more focused for this
      group. Having multibacillary type of disease could also be a risk for development
      of blindness.

PMID- 17017409
TI  - Drug dose calculation need to be drilled.
AB  - A study was conducted to establish the knowledge of correct dose calculations and
      conversion between mass concentration, dilution and percentage concentrations
      amongst medical and paramedical personnel handling patient, with life saving
      support system. A questionnaire was prepared having five standard questions to be
      answered in ten minutes by medical house officers and nurses. Results of the
      study suggested that the knowledge of correct dose calculations of both the
      medical and paramedical personnel needs to be improved to impart best possible
      management to the critically ill patients.

PMID- 17017410
TI  - A boy wearing two different sized slippers in his two feet.
AB  - A rare case of Klippel Trenaunay Weber Syndrome (KTWS) in a 13-year-old boy with
      lower limb asymmetry and lower motor lesion of left lower limb is presented along
      with a brief review of literature.

PMID- 17017411
TI  - Typhoid fever in an 8-month-old infant.
AB  - Typhoid fever occurs both in epidemic and endemic forms and is a public health
      problem in developing countries. Typhoid fever is rare under 2 years of age. The
      clinical profile of typhoid fever in an infant is variable and non-specific. The
      absence of specific symptoms or signs makes the clinical diagnosis of typhoid
      fever difficult. The problem in diagnosing typhoid fever in a young infant is
      highlighted with a brief literature review on the subject. A rare case of typhoid
      fever in an 8 month old infant is reported.

PMID- 17017412
TI  - [Postgraduate training for surgeons and community medicine].

PMID- 17017414
TI  - [Western guidelines on the prevention of postoperative infections and
      compliance].
AB  - Postoperative infections should be comprehensively controlled in the context of
      infection control, rather than as activities of individual surgeons. More
      Japanese surgeons have recently become interested in infection control but not
      many studies have been done in this field in Japan. As a result, surgeons are
      dependent on guidelines published abroad, especially in the USA and Europe. These
      guidelines are generally evidence based and applicable to the Japanese medical
      system. However, some recommendations such as antimicrobial prophylaxis are
      controversial, and evidence from surgery on specific organs is lacking. This
      results in difficulty in accepting the guidelines by Japanese surgeons, as well
      as poor compliance by US surgeons. Furthermore, Japanese surgeons operate mainly
      on Japanese patients and perform invasive operations involving the hepatobiliary
      system and esophagus more frequently than Western surgeons. Evidence for
      infection control during and after such operations should be obtained through
      randomized, controlled trials performed in Japan.

PMID- 17017415
TI  - [Infection control measures in surgical wards and operating theaters].
AB  - A variety of infection control measures are practiced to decrease the risk of
      transmission of pathogens. Standard precautions are thought to be the most
      effective against healthcare-associated infections. However, compliance with
      standard precautions is not sufficiently high in Japanese hospitals. Frequent
      handwashing is an important measure to reduce the risks of transmitting
      infectious organisms from one person to another, although it is not easy to
      maintain high compliance in healthcare settings. This problem has not been
      fundamentally resolved, although infection control practitioners have addressed
      this problem for more than 100 years. It is recommended that healthcare workers
      wear personal protective equipment, such as masks, gowns, gloves, goggles, and
      face shields, to provide barrier protection. Environmental consideration of
      operation rooms must be performed in order to decrease surgical site infections.
      Operating theaters should be cleaned routinely, if possible using a wet vacuum.
      Clean air should be supplied through high-efficiency particulate air filters and
      positive pressure maintained. Surgeons should be aware that they are an important
      potential source of surgical site infection.

PMID- 17017416
TI  - [Antibiotic prophylaxis].
AB  - Though the peri-operative infection involvement of Japan has followed US
      guidelines thus far, we cannot help having some doubts about them because of the
      increase of MRSA in the US now. Considering the present condition of Japan, the
      prevention of MRSA or MDRP and total postoperative infection control, the method
      of antimicrobial agents regimen is needed to consider the aim of preventing the
      appearance of drug-resistant bacteria with decreasing not only SSI but also whole
      postoperative infections.

PMID- 17017417
TI  - [Therapeutic antibiotics for postoperative infection: antibiotic heterogeneity].
AB  - Antibiotic heterogeneity is a strategy to reduce antibiotic pressure, thus
      preventing or minimizing the emergence of antibiotic-resistant strains. Periodic
      changing of (classes of) antibiotics for empiric therapy, so-called antibiotic
      rotation or cycling, has been proposed as one measure to achieve this strategy.
      Promising results of cycling have been reported, mainly from intensive care units
      and largely involves cycling regimens targeted at the treatment of suspected
      infection with gram-negative bacteria. Antibiotic mixing, in which at any given
      time equal fractions of the population receive different antibiotics, is another
      modality to exert heterogenic use of antibiotics. Mixing is usually accomplished
      by administering different classes of antibiotics in consecutive patients.
      Although promising results have been reported, further studies are needed before
      these interventions of cycling and mixing can be widely implemented.

PMID- 17017418
TI  - [Therapeutic antimicrobial agents for postoperative infections: appropriate use
      of antibiotics from the viewpoint of pharmacokinetic/pharmacodynamic theory].
AB  - Pharmacokinetic/pharmacodynamic (PK/PD) parameters can be used predict the
      potential for bacterial eradication with antimicrobial therapy. The validity of
      these parameters is supported by both animal and clinical studies. Two major
      patterns of antimicrobial activities are time-dependent killing and concentration
      dependent killing. Time-dependent killing is characteristic of beta-lactams. The
      major PK/PD parameter correlating with efficacy is a serum concentration of 50
      60% for cephalosporins and 3040% for carbapenems in the dosing interval, and
      these concentrations are the susceptibility limits for the dosing regimens used.
      It is recommended that these types of antibiotic be administered 3-4 times per
      day. Concentration-dependent killing is characteristic of aminoglycosides. The
      major PK/PD parameter correlating with the efficacy of these agents is the 24-h
      area under the curve or peak serum level. This type of antibiotic should be
      administered as the total daily dose once daily.

PMID- 17017419
TI  - [Surgical site infection (SSI) surveillance].
AB  - Surgical site infections (SSI) are major complications after surgery. SSI leads
      to the longer hospital stay, higher costs and patients' dissatisfaction to the
      surgical treatment. SSI surveillance is not only an activity to investigate the
      incidence and causes of SSI but also an infection control activity to reduce SSI
      rates. The Japanese Society of Environmental Infections established the Japanese
      nosocomial infection surveillance UNIS) system and initiated SSI surveillance in
      Japan in 1999. The Japanese Ministry of Health and Welfare started a nation-wide
      SSI surveillance program in July 2002, and the SSI surveillance study group was
      founded in October 2002 to support the Ministry's SSI surveillance and to make
      activities aiming at a further spread and quality enhancement of SSI surveillance
      in Japan. Up to December 2004, 31, 436 cases from 50 institutions have been
      registered. SSI occurred in 2,346 cases (7.7%). With regard to surgical
      procedures, SSI rates are far much higher in gastrointestinal surgery than in
      other procedures. It is important for all Japanese surgeons to continue highly
      precise SSI surveillance and make efforts to reduce SSI rates, to provide safe
      medical practice of high-quality and adequate costs.

PMID- 17017421
TI  - [New concept of wound management].

PMID- 17017422
TI  - [What we can learn from a case of medical malpractice].

PMID- 17017423
TI  - [Operative vascular techniques in lung resections for cancer].

PMID- 17017425
TI  - [Effectiveness of lifestyle modification programs for control of blood pressure:
      a non-randomized controlled trial in Komatsu, Japan].
AB  - PURPOSE: A non-randomized controlled trial was conducted to evaluate the
      effectiveness of three lifestyle modification programs to reduce blood pressure:
      individual counseling only; counseling using group dynamics; and individual
      support using mail. METHODS: We enrolled men and women ages 20-69 with a systolic
      blood pressure (SBP) of 130-159 mmHg and/or a diastolic blood pressure of 85-99
      mmHg (high-normal or mild hypertension). Participants were assigned to one of 4
      groups: individual counseling (n = 134); group counseling (n = 79); mailing
      support (n = 127); and controls (with usual care) (n = 178). The three
      intervention programs included behavioral support for each person's lifestyle
      problems once a month for 6 months. Sex and age adjusted net blood pressure
      change (and 95% confidence intervals [CIs]) compared with the control group was
      calculated for each of the intervention groups. RESULTS: Net SBP change was the
      largest for the group counseling group: sex and age adjusted net SBP change was 
      6.5 mmHg (95% CI: -10.0, -3.0). Net SBP change for the mailing support group was
      also significant (-4.3 mmHg [95% CI: -7.3, -1.3]). Net SBP change for the
      individual counseling group was -2.5 mmHg (95% CI: -5.5, 0.5). Looking at the
      results separately by sex, net SBP reduction was also largest in women of the
      group counseling group, whereas improvement in men was similar among 3 groups
      (approximately 4 mmHg). Body weights were reduced by about 1 kg in all 3 groups.
      CONCLUSIONS: Lifestyle modification programs using group dynamics or using
      individual support by mail, in addition to individual behavioral support, appear
      to be effective for blood pressure reduction. Group counseling may be more
      effective in women.

PMID- 17017426
TI  - [Evaluation of a community-based health education program for salt reduction
      through media campaigns].
AB  - PURPOSE: To provide the strategies, achievement and evaluation of a community
      health education program for salt reduction with media campaigns. METHODS: The
      intervention community was Kyowa town (A district of Chikusei city, census
      population in 1985 = 16,792) where we have systematically conducted a community
      based blood pressure control program since 1981, and health education on
      reduction of salt intake since 1983 for primary prevention of hypertension. The
      education program was performed through media campaigns including use of banners,
      signboards, posters, and calendars with health catchphrases. We also used
      catchphrase-labeled envelopes when sending documents from the municipal health
      center to individuals. Health festivals were held annually to enhance health
      consciousnesses and to improve health behavior. Some of the posters and
      calligraphy were painted or drawn by elementary schoolchildren as part of their
      education. The program was evaluated by repeated questionnaires and examination
      of salt concentrations of miso soup and dietary salt intake. RESULTS: Between
      1983 and 1988, the prevalence of persons who were aware that health consultation
      including blood pressure measurements were available at the town office increased
      from 65% to 84%. The prevalence of those who knew the salt intake goal (10 g or
      less/day) increased from 47% to 63% and that of those who reported to reduce salt
      intake also increased from 38% to 58%. As for salt concentrations of miso soup,
      the proportion with less than 1.1% increased from 47% to 66% between 1985 and
      2004. Age-adjusted mean salt intake for persons aged 40-69 years declined from 14
      g to 11 g in men and from 12 g to 10 g in women between 1982-1986 and 2000-2004.
      CONCLUSION: A long-term systemic education program through media campaigns proved
      feasible with the cooperation of community leaders, schools and food
      associations.

PMID- 17017427
TI  - [Estimation of the range of excess death associated with influenza epidemics:
      application of a model using annual mortality rates and the seasonal index for
      determining minimum excess mortality estimates].
AB  - OBJECTIVE: To determine the range of excess death associated with influenza in
      Japan. METHODS: The monthly rates for mortality from all causes other than
      accidents (ICD9: E800-E949, ICD-10: V01-X59) were determined from the Japanese
      national vital statistics for 1987-2003. By employing a model using the annual
      mortality rates and the seasonal index, the number of expected deaths and the 95%
      range of mortality in the absence of influenza-associated deaths (normal range)
      were obtained. Point estimation of excess mortality during an influenza season
      was performed by calculation of differences between the number of deaths observed
      and the number of deaths expected. The range of excess death was defined: the
      lower limit of the excess death was performed by calculation of difference
      between the number of deaths observed and the upper limit of the normal range.
      The upper limit of the excess death, on the contrary, was performed by
      calculation of difference between the number of deaths observed and the lower
      limit of the normal range. Based on the results of a survey of tendencies in the
      occurrence of infectious diseases, months showing a high prevalence of influenza
      and associated deaths were regarded as "months when the rate of death from
      influenza was 0.9 deaths/100,000 person-years or higher". RESULTS: The excess
      death determined by point estimation was largest in 1999, followed by 1995, 1993,
      1997, 2000, and 2003. The point estimation (range of excess death) in 1999 was
      approximately 49,000 (approximate range, 37,000-60,000). Correspondingly, the
      excess death in 1995 was approximately 38,000 (approximate range, 27,000-48,000).
      While values in 1993, 1997, 2000, and 2003 were in the approximate range of
      21,000 to 25,000, the range of excess death of each year showed the differences:
      approximate range from 15,000 to 36,000 in 1993, from 18,000 to 31,000 in 1997,
      from 18,000 to 28,000 in 2000, and from 11,000 to 34,000 in 2003, respectively.
      From comparison of the range of excess deaths by year, that in 1995 appeared to
      be the largest among the examined years. CONCLUSION: By considering the range of
      variation in the number of deaths in the years when no influenza epidemics
      occurred, the increase (the largest number and smallest number of deaths)
      associated with elevation the prevalence of influenza could be determined.
      Estimation of the range of excess deaths can be considered a useful method for
      understanding the influence of influenza on public health.

PMID- 17017428
TI  - "Cellula omni e cellula" in Turkey.

PMID- 17017429
TI  - Tell us about your lab.

PMID- 17017430
TI  - Light source.

PMID- 17017431
TI  - Clinical experience with the thinPrep Imager System.

PMID- 17017432
TI  - Implementation and evaluation of a new automated interactive image analysis
      system.
AB  - OBJECTIVE: To compare automated interactive screening using the ThinPrep Imaging
      System with independent manual primary screening of 12,000 routine ThinPrep
      slides. STUDY DESIGN: With the first 6,000 cases, the Review Scopes (RS)
      screening results from the 22 fields of view (FOV) only were compared to
      independent manual primary screening. In the next 6,000 cases, any abnormality
      detected in the 22 FOV resulted in full manual screening on the
      cytotechnologist's own microscope. Sensitivity and specificity together with
      their 95% CIs were calculatedfor each method. RESULTS: In the first set of 6, 000
      cases, diagnostic sensitivity and specificity of the imager were 85.19% and
      96.67%, respectively. The diagnostic sensitivity and specificity of manual
      primary screening were 89.38% and 98.42%. This highersensitivity and specificity
      of manual primary screening were found to be statistically significant. The
      second set of 6,000 cases demonstrated no significant statistical difference in
      sensitivity or specificity between the sets of data. CONCLUSION: The results from
      our study show that the sensitivity and specificity of the imager technology are
      equivalent to those of manual primary screening. The system is ideally suited to
      the rapid screening of negative cases, allowing increased laboratory productivity
      and greater throughput of cases on a daily basis.

PMID- 17017433
TI  - Temporal characteristics of laboratory screening errors in cervical cytology.
AB  - OBJECTIVE: To explore the temporal characteristics of laboratory false negative
      reports in cervical cytology. STUDY DESIGN: The temporal characteristics of 198
      false negative cervical cytology cases were compared with those of 750,805
      control cases. RESULTS: The false negative rate did not vary significantly by
      month, day of the week or time of day. The false negative rate was lowest for
      slides that took between 4 and 5 minutes to screen and increased significantly
      with screening times that were longer than 5 minutes. The false negative rate did
      not vary by the number of cases already authorized in a given day. After 40 cases
      had been authorized in a given day, the false negative rate fell for subsequent
      cases, but this did not reach statistical significance. The false negative rate
      was higher during periods when prescreening was performed. CONCLUSION: Further
      studies of the relationship between time and false negative reports are needed.
      These would provide an evidence base to help promote safe working practices
      within laboratories and a more objective setting of maximum daily productivity
      levels for cytotechnologists.

PMID- 17017434
TI  - Methylation profiling of urothelial carcinoma in bladder biopsy and urine.
AB  - OBJECTIVE: To test DNA methylation profiling in detection of urothelial carcinoma
      in urine. STUDY DESIGN: Thirty-three bladder specimens were analyzed for the DNA
      p16INK4a, RASSF1, APC, GSTP, E-Cad and CyclinD2 genes to determine if there is a
      difference in gene methylation between benign and malignant cases. Urine samples
      were analyzed in a feasibility study. Finally, methylation profiles of urine
      samples were obtained and compared with follow-up biopsy diagnoses. RESULTS: We
      found methylated genes in 18% benign, 37% urothelial carcinoma in situ and 93%
      infiltrating urothelial carcinoma cases (p = 0.001). Methylation profiles from
      the 18 urine samples revealed a significantly higher prevalence of methylated
      genes in carcinoma cases than benign cases (100% vs. 50%, p = 0.025). We analyzed
      methylation profiles in 37 cytologically atypical urine samples with malignant or
      benign diagnosis on surgical follow-up andfound that only APC (55% in malignant
      vs. 0% in benign, p=0.025) and CyclinD2 were differentially methylated (35% in
      malignant vs. 0% in benign, p=0.2) while p14ARF, p16INK4a, RASSF1, GSTP and E-Cad
      had similar methylation profiles. CONCLUSION: These results suggest that
      methylation of p14ARF, p16INK4a, RASSF1, GSTP and E-Cad genes may not accurately
      identify carcinoma, but methylated APC and CyclinD2 might be useful biomarkers
      for urothelial carcinoma in urine.

PMID- 17017435
TI  - Role of fine needle aspiration cytology in nodular sclerosis variant of Hodgkin's
      lymphoma.
AB  - OBJECTIVE: To assess the efficacy of fine needle aspiration cytology (FNAC) in
      the diagnosis of nodular sclerosis variant of Hodgkin's lymphoma (NSHL) and to
      analyze cytologic features that could help in subtyping a case of Hodgkin's
      lymphoma into this variant. STUDY DESIGN: FNAC smears of 18 histopathologically
      proven cases of NSHL were analyzed for a variety of features. RESULTS: On initial
      cytologic assessment, 14 of 18 cases were diagnosed as Hodgkin's lymphoma. No
      further subtyping was performed. In this retrospective analysis it was possible
      to revise the diagnosis in the remaining 4 cases. Of the various cytologic
      features analyzed, presence of numerous lacunar-type cells along with fibroblasts
      and collagenous material were useful pointers toward a diagnosis of nodular
      sclerosis variant. Fibroblasts were seen in 83.33%, collagenous material in
      27.77% and numerous lacunar cells in 77.77%. CONCLUSION: Subtyping of NSHL based
      on cytologic features alone has been a matter of debate for a long time. Of the
      various subtypes, nodular sclerosis poses the greatest diagnostic difficulty.
      Though certain cytologic features may help in suggesting a diagnosis of nodular
      sclerosis variant, the primary role of fine needle aspiration is to diagnose a
      case of Hodgkin's lymphoma as such and advise histopathologic examination for
      further categorization.

PMID- 17017436
TI  - Role of fine needle aspiration cytology in nonneoplastic testicular and scrotal
      lesions and male infertility.
AB  - OBJECTIVE: To study the role of fine needle aspiration (FNA) in male infertility
      and in nonneoplastic lesions of the testis and scrotum. STUDY DESIGN: In a
      retrospective study over a 5-year period, 164 cases of FNA of testicular and
      scrotal nonneoplastic lesions were retrieved. Aspiration was performed with a 23
      gauge needle on a 20-mL syringe. RESULTS: Of 164 cases, 27 (16%) remained
      inconclusive; they were mainly from epididymal lesions. The remaining 137 cases
      were categorized as inflammatory lesions, 52 (31.7%); noninflammatory lesions, 42
      (25.6%); and infertility cases, 43 (26.2%). Among the inflammatory lesions, 33
      cases had nonspecific inflammation, 13 had granulomatous epididymoorchitis, 3
      cases were of spermatic granuloma, and 3 cases revealed microfilariae.
      Noninflammatory lesions included 25 cases of spermatocele, 8 of hematoma/torsion,
      5 of hydrocele, 3 of benign epididymal cyst and 1 of calcinosis cutis. Among the
      patients investigated for infertility, 23 (53%) had normal spermatogenesis, 6
      (14%) had Sertoli cells only, 5 (119%) had maturation arrest, 6 (14%) showed
      hypospermatogenesis, and 3 (7%) showed an atrophic pattern. CONCLUSION: FNA of
      the testis and scrotum is a simple, quick, minimally invasive and painless
      outpatient procedure. The sample obtained is more representative than biopsy as
      several separate punctures can be made, and there is no local scarring.

PMID- 17017437
TI  - Proteomic identification of new biomarkers and application in thyroid cytology.
AB  - OBJECTIVE: To validate proteins identified by proteomics as potentially usable
      markers in thyroid pathology. STUDY DESIGN: Frozen sections of thyroid tumors
      were manually micro-dissected and proteins extracted. Two-dimensional (2D) gel
      electrophoresis and subsequent liquid chromatography/mass spectroscopy were
      performed, and differentially expressed proteins were identified. Validation of
      candidates for tumor markers (galectin-1, galectin-3, S100C and voltage-dependent
      anion channel 1 [VDAC1]) was done by immunohistochemistry in 21 cell blocks from
      fine needle aspiration biopsies (FNAB) and corresponding histology specimens (13
      cases). RESULTS: Galectin-3 was negative in benign lesions and positive in FNAB
      from papillary carcinoma (5 of 5), follicular variant of papillary carcinoma (1
      of 4) and follicular carcinoma (1 of 2). S100C was positive in some benign
      lesions: hyperplasia (2 of 4), goiter (1 of 3) and follicular adenoma (1 of 3),
      with predominantly nuclear pattern of staining. S100C was positive in malignant
      lesions, showing cytoplasmic location. Galectin-1 was negative in benign lesions
      and positive in follicular carcinoma (1 of 2), papillary carcinoma (2 of 5) and
      follicular variant of papillary carcinoma (1 of 4). VDAC1 was detected in benign
      and malignant lesions, showing a strong positivity in follicular carcinomas.
      CONCLUSION: Immunohistochemical validation of potential markers is a crucial step
      before clinical application in diagnosis. Galectin-3, galectin-1 and S100C can be
      used to help in discriminating benign and malignant thyroid lesions.

PMID- 17017438
TI  - Schwannomalike mixed tumor of the parotid gland: a case report.
AB  - BACKGROUND: Schwannomalike mixed tumor is a rare benign tumor of the parotid
      glands. CASE: A 75-year-old woman presented with a tumor 3 cm in diameter
      localized in her left parotid gland. Fine needle aspiration (FNA) of the lesion
      revealed 2 types of cells: 1 with elongated, wavy, hyperchromatic nuclei and a
      scant cytoplasmic border and 1 with larger, weakly staining nuclei and more
      abundant cytoplasm. Morphologic examinations were performed. CONCLUSION: FNA
      cytology was very useful in the diagnosis of this rare tumor of the parotid
      gland.

PMID- 17017439
TI  - Diagnosis of icteric-type hepatocellular carcinoma by fine needle aspiration: a
      case report.
AB  - BACKGROUND: Bile duct invasion is very rare in patients with hepatocellular
      carcinoma (HCC). It usually presents difficult problems with the clinical
      differential diagnosis. Moreover, another difficulty might arise when an
      obstructive jaundice patient is found to have past history of 2 separate
      malignancies. Fine needle aspiration (FNA) becomes the method of choice for
      clarification of the bile duct tumor thrombus. CASE: A 72-year-old man presented
      with progressive obstructive jaundice for 1 month. Past history revealed the
      occurrence of 2 distinct malignancies during the previous 3 years; they had been
      resected successfully. Initial imaging studies, including abdominal sonography
      and computed tomography, were negative for the liver. However, FNA demonstrated
      clusters of pleomorphic and hyperchromatic cancer cells with an increased
      nuclear/cytoplasmic ratio proliferating in a vague trabecular pattern with some
      appearance of sinusoids. Multinucleated giant cells were seen. No bile duct
      epithelial cells were seen. The diagnosis of the third separate malignancy,
      moderately differentiated HCC, was made. CONCLUSION: To our knowledge, this is
      the first report of icteric-type HCC diagnosed by FNA although the primary lesion
      was undetectable on routine, noninvasive examinations. FNA cytology is an
      accurate and minimally invasive method for early confirmation of biliary HCC
      thrombi.

PMID- 17017440
TI  - Interwoven dendritic processes of follicular dendritic cell sarcoma demonstrated
      on ultrafast papanicolaou-stained smears: a case report.
AB  - BACKGROUND: Follicular dendritic cell (FDC) tumor is a rare tumor derived from
      accessory cells in the lymphoid follicles. FDC tumors are typically diagnosed on
      histology based on immunoreactivity to at least 1 of the FDC markers (CD21, CD23
      or CD35) or based on the characteristic ultrastructural feature of long,
      interwoven, cytoplasmic, dendritic processes connected by desmosomes. CASE: We
      observed novel cytologic features of FDC sarcoma in a liver fine needle aspirate
      of a 46-year-old man status post surgery and chemotherapy for FDC sarcoma,
      originating in the gastrointestinal tract with metastases to the liver, pancreas
      and spleen. In the Diff-Quik- and Papanicolaou-stained smears, the tumor cells
      presented in syncytial fragments as well as single cells, as previously reported
      in the cytologic literature. However, the single cells were interconnected to
      neighboring single cells via long, thin, threadlike cytoplasmic processes in
      ultrafast Papanicolaou (UFP)-stained smears. The tumor cells possessed multipolar
      cytoplasmic processes rather than unipolar ones, as previously reported.
      CONCLUSION: The ultrastructural features of a web of interwoven, dendritic,
      cytoplasmic processes of FDC tumor was demonstrated for the first time on
      cytology. Observation of this feature may allow the diagnosis to be made on
      cytology prior to histology, immunohistochemistry or electron microscopy.

PMID- 17017441
TI  - Immunoglobulin crystal-storing histiocytosis in a pleural effusion from a woman
      with IgA kapa multiple myeloma: a case report.
AB  - BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare disorder occurring in
      patients with lymphoproliferative diseases, predominantly multiple myeloma and
      low grade B-cell lymphoma. This report presents the first case of CSH diagnosed
      on pleural fluid from a patient with multiple myeloma (MM). CASE: A 79-year-old
      women with IgA kappa MM underwent thoracocenthesis and thoracic drainage because
      of a pleural effusion. Cytologic and immunocytochemical examination of pleural
      fluid revealed abundant histiocytic, CD68-positive cells with prominent
      intracytoplasmic, needlelike, crystalloid inclusions showing strong
      immunopositivity for IgA heavy and kappa light chains. Identical crystals were
      observed on an extracellular background. No myeloma infiltration was detected.
      Two weeks later, examination of new pleural fluid from the patient showed a
      similar cytologic picture, but, in addition, isolated plasma cell features were
      identified. They were too few for a meaningful determination of clonality. The
      patient died I month after the CSH diagnosis. CONCLUSION: This case illustrates
      the value of cytologic examination of serous fluids from patients with plasma
      cell dyscrasias, not only to evaluate possible infectious or neoplastic causes
      but also to diagnose CSH.

PMID- 17017442
TI  - Cytologic diagnosis of a metastatic oligodendroglioma in a pleural effusion. A
      case report.
AB  - BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is
      diagnosed primarily by biopsy or autopsy and very occasionally by fine needle
      cytologic examination. We report a case of metastatic oligodendroglioma diagnosed
      by cytologic examination of a pleural effusion. Such a diagnosis has not been
      reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural
      effusion 7 years after an operation for an oligodendroglioma over the left
      frontal lobe. Cytologic examination of the pleural effusion showed aggregates of
      atypical polygonal cells containing round, hyperchromatic nuclei and scanty,
      granular cytoplasm in Liu's and Papanicolaou stain and cell blocks.
      Immunohistochemical staining of the tumor cells revealed a positive reaction for
      antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy
      confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of
      the right humeral and femoral bones was noted 1 month later, and the specimen
      also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To
      the best of our knowledge, this is the first metastatic oligodendroglioma
      diagnosed by pleural cytology. Fine needle cytology can provide a reliable and
      rapid way to detect an extracranial metastatic oligodendroglioma in different
      organs.

PMID- 17017443
TI  - Recurrent calcifying epithelial odontogenic tumor of the maxilla: report of a
      case with cytologic diagnosis.
AB  - BACKGROUND: Calcifying epithelial odontogenic tuor (CEOT) occurs rarely in the
      maxilla and lacks classical clinicoradiologic features. The cytologic features in
      conjunction with the radiologic picture can be helpful in making a preoperative
      diagnosis and guiding management. CASE: A young man with a progressively
      increasing left cheek swelling and proptosis of the left eye was referred for
      fine needle aspiration cytology. The smears were paucicellular and showed
      clusters of mildly pleomorphic squamoid cells; abundant, amyloidlike, pink
      material; and occasional concentric calcification. A provisional diagnosis of
      CEOT was given and confirmed on histopathology. CONCLUSION: The characteristic
      cytologic findings in association with radiologic features can help the
      cytopathologist in rendering a firm preoperative diagnosis of CEOT even at
      atypical sites such as the maxilla.

PMID- 17017444
TI  - Histiocytoid change in breast carcinoma: a report of 3 cases with an unusual
      cytomorphologic pattern of apocrine change.
AB  - BACKGROUND: Breast carcinomas composed predominantly or exclusively of cells with
      foamy and/or granular cytoplasm have been termed histiocytoid breast carcinoma.
      CASES: Three cases of HBC had fine needle aspirates that were moderately cellular
      and composed of cells with abundant foamy and/or granular cytoplasm, arranged in
      loosely cohesive groups and dispersed singly. The cells showed subtle cytologic
      atypia, including nuclear hyperchromasia and slightly irregular nuclear outlines.
      Definitive cytologic diagnosis was not possible in the 3 cases, and they were
      reported as "suspicious for malignancy." Core biopsies of 2 cases showed a
      typical Indian file pattern of invasive lobular carcinoma, while the third case
      was composed of sheets of discohesive histiocytoid cells admixed with a prominent
      lymphoid infiltrate. All 3 cases were E-cadherin negative, confirming their
      lobular nature. CONCLUSION: HBC represents an unusual morphologic pattern of
      apocrine change that may be seen in lobular and ductal breast carcinomas.
      Recognition of these lesions is vital in that they may be mistaken for a variety
      of other entities composed of foamy/granular cells; some of those entities have
      vastly different implications for treatment and prognosis.

PMID- 17017445
TI  - Fine needle aspiration biopsy diagnosis of angiosarcoma after breast-conserving
      therapy for carcinoma supported by use of a cell block and immunohistochemistry.
AB  - BACKGROUND: Angiosarcoma is a rare malignant soft tissue tumor occurring at
      various sites as either a primary or secondary event. Primary angiosarcoma of the
      breast is an unusual tumor, counting for 1 in 1700-2,000 primary malignant tumors
      of this organ. An increasing number of secondary angiosarcomas involving skin and
      breast. CASE: Angiosarcoma arose 6 years after breast-conserving therapy for
      invasive carcinoma in a 69-year-old woman. Fine needle aspiration of several
      small, reddish, intradermal nodules over the treated area revealed malignant
      cells with an endothelial immunophenotype in the cel block, yielding the
      diagnosis of angiosarcoma, subsequently confired in a mastectomy speciman.
      CONCLUSION: Fine needle aspiration, supported by ancillary techniques, such as
      cell block and immunohistochemistry, allows the cytologic diagnosis of an
      angiosarcoma and differentiates it from a carcinoma recurrence.

PMID- 17017446
TI  - Submandibular rhabdomyoma: a case report.
AB  - BACKGROUND: The cytologic diagnosis of extracardiac rhabdomyoma is frequently
      hampered by its rarity and resemblance to various tumors. In this regard, the
      infrequent occurrence has hindered its prompt and early recognition. It is also
      confused with other tumors because of similarities in clinical and cytologic
      presentations. CASE: A submandibular rhabdomyoma occurred in an otherwise
      healthy, 62-year-old man. The neoplasm was firstly diagnosed by fine needle
      aspiration cytology (FNAC. Complete local excision without radical surgery was
      performed. Histologic findings confirmed the cytologic diagnosis of adult
      rhabdomyoma. Treatment-related complications were minimal, and there was no
      evidence of recurrent disease 6 years later. CONCLUSION: Helpful FNAC features
      and immunocytochemical results permitted an early diagnosis and spared the
      patient unnecessary radical surgery.

PMID- 17017447
TI  - Fine needle aspiration of poorly differentiated oxyphilic (Hurthle cell) thyroid
      carcinoma: a case report.
AB  - BACKGROUND: Poorly differentiated oxyphilic (Hurthle cell) carcinomas are a more
      recently described variant of poorly differentiated thyroid carcinoma and are
      characterized by a prominent Hurthle cell component in a solid or trabecular
      arrangement. Clinically, poorly differentiated oxyphilic carcinomas behave more
      aggressively as compared to classic Hurthle cell carcinomas, which have a
      predominantly follicular pattern. Although the histology of these rare thyroid
      tumors has been reported in the literature, the cytologic features on fine needle
      aspiration biopsy have not been described before. CASE: A 73-year-old man with a
      long history of radioactive iodine and levothyroxine therapy for multinodular
      goiter presented with a painful, rapidly expanding, 6-cm, left thyroid mass with
      aggressive radiologic features. Fine needle aspiration biopsy of the mass yielded
      extremely cellular smears with a dual population of medium-sized follicular cells
      and numerous Hurthle cells. Subsequent thyroidectomy confirmed the malignant
      nature of this Hurthle cell-rich tumor, warranting a diagnosis of poorly
      differentiated oxyphilic (Hurthle cell) thyroid carcinoma. CONCLUSION: Poorly
      differentiated oxyphilic thyroid carcinoma is an aggressive variant of Hurthle
      cell carcinomas and must enter the differential diagnosis when fine needle
      aspiration biopsy of a radiologically aggressive thyroid mass yields extremely
      hypercellular smears with a prominent Hurthle cell component.

PMID- 17017448
TI  - Massive infarction of papillary carcinoma of the kidney after fine needle
      aspiration biopsy: report of a case with cytohistologic correlation.
AB  - BACKGROUND: Papillary carcinomas are rare malignant tumors of the kidney that
      sometimes are diagnosed preoperatively from their characteristic computed
      tomography appearance. CASE: A patient with papillary carcinoma of the kidney
      developed a selective and massive infarction of the neoplastic tissue after fine
      needle aspiration biopsy. CONCLUSION: Papillary carcinoma of the kidney should be
      added to the list of neoplasms prone to undergo ischemic infarction after fine
      needle aspiration.

PMID- 17017449
TI  - Tibial adamantinoma with local recurrence and pulmonary metastasis: report of a
      case with histocytologic findings.
AB  - BACKGROUND: Adamantinoma is a rare primary bone neoplasm of low malignant
      potential that may recur or metastasize in a mall percentage of patients. The
      myriad histologic patterns may cause difficulty in distinguishing this tumor from
      other primary or metastatic neoplasms. The cytomorphologic findings of fine
      needle aspiration biopsy were reported previously in only a small number of
      cases. CASE: A 32-year-old man presented with a mass in the distal side of the
      left leg that was diagnosed as classic adamantinoma by open biopsy. Local
      recurrence and pulmonary metastases were confirmed by fine needle aspiration
      biopsy, which showed low grade, uniform cells with nuclear membrane grooves. The
      patient underwent a below-the-knee amputation and is receiving palliative
      treatment for progressive pulmonary spread. CONCLUSION: The diagnosis of
      adamantinoma requires knowledge of compatible clinical and radiologic studies as
      well as understanding of the variable histologic patterns that one may encounter.
      Fine needle aspiration biopsy is particularly useful in the diagnosis of
      recurrent and metastatic adamantinoma. This case report describes a distinctive
      cytomorphologic feature of nuclear grooves that may be a useful aid in
      distinguishing the tumor cells of adamantinoma from other cell types.

PMID- 17017450
TI  - Cytodiagnosis of hepatic amyloidosis by fine needle aspiration cytology: a case
      report.
AB  - BACKGROUND: Amyloid in fine needle aspirates tends to be overlooked due to its
      rarity. It may appear at virtually any site and can be identified by special
      stains. CASE: In a case of amyloidosis of the liver, where fine needle aspiration
      cytology was instrumental in making the primary diagnosis. Smears revealed normal
      hepatocytes and chronic inflammatory cells. Amorphous material (amyloid) was
      extensively present between compressed hepatocytic clusters. It stained pale
      green in Papanicolaou-stained preparations and reddish purple with Giemsa stain.
      This material was initially thought to be hyalinized granulomas. However, it was
      later confirmed to be amyloid by using Congo Red stain. CONCLUSION: Whenever
      amorphous material is present in smears, a high index of suspicion for amyloid
      needs to be maintained.

PMID- 17017451
TI  - Malignant fibrous histiocytoma of the chest wall masquerading as medullary breast
      carcinoma: a case report.
AB  - BACKGROUND: Cytologic diagnosis of malignant fibrous histiocytoma can be
      problematic, as these neoplasms are known to mimic multiple other conditions.
      CASE: A fine needle aspirate from a 60-year-old woman was diagnosed at 2
      institutions as medullary carcinoma of the breast. The patient received neo
      adjuvant chemoradiotherapy before the tumor war excised. Gross pathologic
      examination and histomorphology on routine staining were compatible with the
      cytologic diagnosis. The accurate diagnosis of pleomorphic-storiform-type
      malignant fibrous histiocytoma was a surprise and was established with
      immunocytochemical stains. In retrospect, it was thought that clinical and
      radiologic overlap, creating a high index of suspicion for a breast neoplasm and
      compounding the cytologic appearance of a medullary carcinoma with spindle cell
      metaplasia and syncytial cells, was responsible for the error. CONCLUSION: This
      case highlights a potential cytodiagnostic pitfall and the importance of
      establishing a definitive tissue diagnosis in the face of equivocal cytologic
      findings.

PMID- 17017452
TI  - Partial expectoration of a typical carcinoid: report of a case with diagnosis on
      sputum cytology.
AB  - BACKGROUND: Typical carcinoid (TC) tumors are relatively infrequent. Diagnosis on
      the basis of sputum cytology is difficult, and there are few cases reported in
      the literature. Partial expectoration of endobronchial tumors is a rare event
      that permits their cytologic diagnosis. CASE: A 71-year-old, male nonsmoker
      sought medical attention for a cough and expectoration of 1 month's duration.
      After 2 negative sputum tests, the third sample revealed large tumor fragments as
      a result of partial expectoration of an endobronchial, growing mass. CONCLUSION:
      The diagnosis of TC is rarely made by sputum examination as the tumor is
      generally covered with intact bronchial mucosa. However, in our case there was
      partial expectoration of the tumor. This has been reported just once before in
      the literature.

PMID- 17017453
TI  - Cytologic and histologic findings in multiple renal hybrid oncocytic tumors in a
      patient with Birt-Hogg-Dube syndrome: a case report.
AB  - BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant neoplastic
      syndrome characterized by multiple skin lesions, lung cysts and renal tumors. A
      variety of histologic types of renal tumors have been reported, including clear
      cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma and a
      recently described hybrid oncocytic tumor, which is thought to be highly
      associated with BHD. CASE: We report a case of a 48-year-old woman with BHD who
      initially presented to our institution with spontaneous pneumothorax and was
      found to have multiple lung cysts and renal tumors on computed tomography. We
      describe the fine needle aspiration findings of one of the renal tumors, which
      was suggestive of so-called hybrid oncocytic tumor. We also describe the gross
      and histologic findings of the multiple kidney tumors that the patient
      subsequently had excised. CONCLUSION: When multiple kidney tumors from a single
      patient appear oncycytic on fine needle aspiration, especially when focal clear
      cells are present, the possibility of oncocytomas and hybrid tumors associated
      with BHD must be entertained.

PMID- 17017454
TI  - Granular cell tumor of breast: diagnosis by fine needle aspiration cytology.

PMID- 17017455
TI  - Diagnostic help of HER-2/neu expression in suspicious cases of breast fine needle
      aspiration.

PMID- 17017456
TI  - The nature of "broken egg" events in exfoliated human cells.

PMID- 17017458
TI  - The tingling of my heart. Little did I know I had a cardiac condition.

PMID- 17017457
TI  - HPV testing in liquid specimens.

PMID- 17017459
TI  - Drugs to avoid, drugs to take. Avoiding facial wasting and fat accumulation.

PMID- 17017460
TI  - Banishing chipmunk cheeks and bullfrog neck. Treating these and other body
      changes from HIV drugs.

PMID- 17017462
TI  - Women's sexual health. Taking care of our winks.

PMID- 17017461
TI  - Living with HIV and hepatitis C. What you need to know, in brief.

PMID- 17017463
TI  - How to survive a trip to the hospital. The intern who takes your history just
      graduated from medical school.

PMID- 17017464
TI  - One on one: U.S. Senator Barack Obama (D-IL). The politics of HIV. Interview by
      Jeff Berry.

PMID- 17017465
TI  - HIV and the kidneys. How to know when something is wrong and why it is important.

PMID- 17017466
TI  - A spreadsheet template for the analysis of optical coherence tomography in the
      longitudinal management of diabetic macular edema.
AB  - BACKGROUND AND OBJECTIVE: To provide a tool for analyzing optical coherence
      tomography data in patients with diabetic macular edema. PATIENTS AND METHODS:
      Retrospective series of 206 patients with diabetic macular edema involving at
      least one eye and receiving focal laser photocoagulation, intravitreal
      triamcinolone acetonide injection, or vitrectomy, membrane peeling, and
      intravitreal triamcinolone acetonide injection, and of untreated fellow eyes
      without diabetic macular edema. Main outcome measures included foveal subfield
      mean thickness and thickening relative to normal (microns), total macular volume
      and its increase relative to normal (mm3), visual acuity (Snellen decimal), and
      intraocular pressure (mm Hg). RESULTS: The authors demonstrate a graphical
      display of data based on a spreadsheet template for the longitudinal management
      of diabetic macular edema. Complex relationships of ocular response and
      interventions are concisely displayed. CONCLUSION: A graphical display of optical
      coherence tomography, visual acuity, and intraocular pressure data is a practical
      aid in the management of diabetic macular edema.

PMID- 17017467
TI  - Medicare and Medicaid programs; fire safety requirements for certain health care
      facilities; amendment. Final rule.
AB  - This final rule adopts the substance of the April 15, 2004 tentative interim
      amendment (TIA) 00-1 (101), Alcohol Based Hand Rub Solutions, an amendment to the
      2000 edition of the Life Safety Code, published by the National Fire Protection
      Association (NFPA). This amendment allows certain health care facilities to place
      alcohol-based hand rub dispensers in egress corridors under specified conditions.
      This final rule also requires that nursing facilities at least install battery
      operated single station smoke alarms in resident rooms and common areas if they
      are not fully sprinklered or they do not have system-based smoke detectors in
      those areas. Finally, this final rule confirms as final the provisions of the
      March 25, 2005 interim final rule with changes and responds to public comments on
      that rule.

PMID- 17017469
TI  - Medical devices; reprocessed single-use devices; requirement for submission of
      validation data. Direct final rule.
AB  - The Food and Drug Administration (FDA or we) is amending certain classification
      regulations for reprocessed single-use devices (SUDs) whose exemption from
      premarket notification (510(k)) requirements have been terminated and other
      reprocessed SUDs already subject to premarket notification for which validation
      data, as specified under the Medical Device User Fee and Modernization Act of
      2002 (MDUFMA), are necessary in a 510(k). Elsewhere in this issue of the Federal
      Register, we are publishing a companion proposed rule, under FDA's usual
      procedures for notice and comment, to provide a procedural framework to finalize
      the rule in the event we receive any significant adverse comment and withdraw the
      direct final rule. This action codifies actions taken in previous Federal
      Register notices in accordance with MDUFMA.

PMID- 17017468
TI  - Medicare program; rural health clinics: amendments to participation requirements
      and payment provisions; and establishment of a quality assessment and performance
      improvement program; suspension of effectiveness. Interim final rule with comment
      period; partial suspension of effectiveness.
AB  - This interim final rule with comment period revises the rural health clinic (RHC)
      regulations to revert to those provisions set forth in regulations before
      publication of the December 24, 2003 RHC final rule. That final rule implemented
      certain provisions of the Balanced Budget Act (BBA) of 1997 to establish a
      process and criteria for disqualifying from the RHC program clinics that no
      longer meet basic location requirements (rural and medically underserved), and to
      require RHCs to establish quality assessment and performance improvement
      programs. That rule also prohibited "commingling" (the use of the space,
      professional staff, equipment, and other resources) of an RHC with another
      entity. [In addition, it addressed comments on the February 28, 2000 proposed
      rule. Since the publication of the RHC final rule exceeded the 3-year timeline
      for finalizing proposed rules set by the Medicare Prescription Drug, Improvement,
      and Modernization Act of 2003, we are suspending the effectiveness of the current
      provisions by removing the RHC provisions set forth in the December 2003 final
      rule and reverting to those RHC provisions previously in effect.] We intend to
      reissue new proposed and final RHC rules to reinstate the current provisions.
      However, these revisions do not impact the effectiveness of the self-implementing
      provisions of the BBA or any provisions we had previously implemented or enforced
      through program memoranda.

PMID- 17017470
TI  - Retail sales of scheduled listed chemical products; self-certification of
      regulated sellers of scheduled listed chemical products. Interim final rule with
      request for comment.
AB  - In March 2006, the President signed the Combat Methamphetamine Epidemic Act of
      2005, which establishes new requirements for retail sales of over-the-counter
      (nonprescription) products containing the List I chemicals ephedrine,
      pseudoephedrine, and phenylpropanolamine. The three chemicals can be used to
      manufacture methamphetamine illegally. DEA is promulgating this rule to
      incorporate the statutory provisions and make its regulations consistent with the
      new requirements. This action establishes daily and 30-day limits on the sales of
      scheduled listed chemical products to individuals and requires recordkeeping on
      most sales.

PMID- 17017471
TI  - [Congenital cholesteatoma].
AB  - The authors analysed cases of congenital cholesteatoma from 1987 to 2003 which
      were operated in ENT Department of District Hospital in Rzeszow. Among 1682
      operations there were only 10 cases of congenital cholesteatoma (0.59%). The
      authors analysed sex and age of the patients, symptoms, type of operations
      performed and final diagnosis.

PMID- 17017472
TI  - [Professional views of pharmacy faculty graduates].
AB  - The purpose of this study was to define new professional ideals of pharmacists
      and to prove or refute a hypothesis stating that role model of the
      representatives of this profession is currently changing. In a survey a group of
      Pharmacy Faculty graduates were asked about the motives for the choice of their
      pharmacy studies, constancy of the conviction of this choice's validity, the
      desired place of work, expectations concerning their professional function, the
      opinion on the future of that profession in Poland, the attitude to pharmacists'
      chamber and to the phenomenon of self-therapy. The responses collected provided
      information on the professional views of the queried group. The author also
      defined the notion of professional views themselves, vocation, professional
      attitude and professional model. The results show that the respondents in their
      majority wish to become pharmacists (64%). High estimation of this profession
      influenced their choice of studies (71%). Only 18% felt called to do it. The
      queried group, as a whole, are not satisfied with their pharmacy studies, and
      only 38% would firmly undertake to study it again. The subjects declare to be
      fairly active in performing their civic duties (58% take part in elections), yet
      remain relatively passive within the context of their own professional government
      (15%). From their professional activity they expect personal satisfaction and
      money. Most subjects predict that adverse changes are going to take place in
      pharmacy (to 2005): pharmaceutical concerns will buy out pharmacies, the number
      of pharmaceutical wholesale stores will decrease considerably, pharmaceuticals
      will be delivered straight to patient's door, the system of obtaining drugs on
      doctor's prescription will decline. However, they doubt that the physicians are
      going to take over the sale of pharmaceuticals, that the number of new pharmacies
      is going to increase, that few will become owners of most pharmacies, and that
      the Polish pharmaceutical industry will collapse. Pessimistic views of the
      respondents outnumber the optimistic ones, however only 4% are doubtful about
      their own, professional success. In evaluating the phenomenon of self-therapy the
      respondents show judiciousness, perceiving more negative than positive aspects of
      it. The views of the studied group are precise and clear, while in the assessment
      of own professional role the pro-social attitude prevails.

PMID- 17017473
TI  - [Total plasma ghrelin level in anorexia nervosa female].
AB  - Ghrelin is a peptide exhibiting strong orexigenic, adipogenic and somatotropic
      properties. About 80% of the peptide is produced in the stomach and it is an
      essential link of the brain-gut axis. Ghrelin through vagal fibres and circular
      system stimulates the hunger center in hypothalamus, controlling food uptake and
      body weight gain. This mechanism fails in eating disorders. The aim of the study
      was the analysis of total ghrelin levels in anorexia nervosa (AN) girls during
      cognitive-behaviorally treatment. MATERIAL AND METHODS: A group of 50 AN girls
      with the restrictive form ofAN (according to the DSM-IV, ICD-10 criteria)
      behaviorally treated and participating in psychotherapy. The mean BMI in
      anorectic group was 15.1 kg/m2 and mean ghrelin level 6562 pg/ml. The group of 20
      healthy girls with mean BMI of 21.4 kg/m2 and mean ghrelin level 4856 pg/ml
      served as a control group. The mean age in study group was 17.5 and 18.5 in
      control girls. Statistical analysis of significance was carried out by the
      Student's t-test, Mann-Whitney U test, Spearman's correlation and linear Person's
      correlation. To assess the dynamic change of parameters Anova-Friedman and Anova
      Kruskal-Wallis tests were used. The p < 0.05 was accepted as statistically
      significant. RESULTS: Initial mean plasma ghrelin levels in AN girls was
      significantly higher than in control group. After 24 weeks of treatment the mean
      BMI increased to 17.5 kg/m2, ghrelin level decreased to the value of 3919 pg/ml.
      CONCLUSION: In AN female the decreasing of total plasma ghrelin level is a result
      of changing pathological feeding behaviour.

PMID- 17017474
TI  - [The role of a family delivery in the modern obstetrics].
AB  - The aim of the study were the comparison of a course of delivery and the baby's
      condition between family delivery and traditional mode of labour, and the
      analysis of factors influencing the choice for a particular delivery option.
      MATERIAL AND METHODS: retrospective analysis of the medical records of healthy
      pregnant women at term hospitalised in 2001-2003 in the Department of
      Perinatology and Gynecology, Zabrze, Poland. Patients were divided into two
      groups depending on a delivery mode basis: group I (n = 520) were those attended
      by a family member, group II involved patients who were not (n = 1480). RESULTS:
      In the analysed period of time the rate of family deliveries has risen from 14%
      only in 2001 till 26% in 2002 and 36% in 2003. Younger patients, particularly
      occupationally active primigravidae with at least secondary education were more
      likely to choose the family delivery. This group of patients revealed two times
      lower rate of caesarean section or abnormal foetal heart rate. At the same time
      longer the first and the second stage of labour were noted. Duration of the III
      stage did not differ. CONCLUSIONS: Support by a family member during delivery
      could significantly elongate time spent in the delivery room as well as decrease
      the number of invasive procedures during and after the delivery.

PMID- 17017475
TI  - [The comparison of mean body weight among breast-fed and bottle-fed children from
      1 to 18 month of life].
AB  - There were performed many analyses comparing physical development between breast
      fed and bottle-fed infants and estimated that breast-fed children have different
      growth than bottle-fed. The aim of the study was the comparison of body weight
      rate among breast-fed and bottle-fed children from 1-18 month of life. MATERIAL
      AND METHODS: 352 children were enrolled into the analysis: 218 breast-fed and 134
      bottle-fed children. We documented age, sex, environment of life, birth weight
      and weight at the moment of hospitalisation. We compared: mean weight at the
      moment of hospitalisation, mean increment of weight, mean monthly increment of
      weight in breast- and bottle-fed children. RESULTS: Breast-fed girls achieved
      higher mean monthly weight increment in 1st quarter of life than bottle-fed.
      Bottle-fed girls achieved higher mean body weight and increment of weight than
      breast-fed in 4th quarter. Bottle-fed boys achieved higher mean weight, mean
      increment of weight in 1st, 3rd and 6th quarter of life and higher monthly
      increment of weight in the 1st quarter of life than breast-fed. CONCLUSION: On
      the basis of performed analysis we confirm that breast-fed and bottle-fed
      children in the first 18 months of life increase body weight at a different rate.

PMID- 17017476
TI  - [Analysis of labour and perinatal complications in case of foetus weight over
      4000 g].
AB  - The fetal macrosomia occurs in 3-15% pregnancies. It is recognized when foetus
      weight exceeds 4000 g in any period of pregnancy. Macrosomia can also be
      determined in case of foetus weight over 90 percentyl for the appropriate
      pregnancy period. The most detrimental foetal complications of macrosomia are:
      shoulder dystocia with Erb's brachial palsy, facial nerve palsy, clavicular and
      humeral bone fracture. The attempts in order to eliminate these complications
      lead to increase in the number of caesarean sections and labour inductions.
      Clinical examination and assessment of risk factors as well as ultrasonographic
      examination cannot exclude or confirm the possibility of macrosomia with
      sufficient specificity and sensitivity. On the other hand it is well known that
      delivery of macrosomic foetus is not always associated with perinatal
      complications. The aim of the study was to assess the risk of perinatal
      complication in foetuses with large birth weight. MATERIAL AND METHODS: In case
      control study the data from medical records of 652 newborns with birth weight
      over 4000 g were analysed. Only single born at term foetuses in cephalic
      presentation were included into the analysis. RESULTS: The Erb's brachial palsy,
      clavicular bone fracture, shoulder dystocia and convulsions in newborn were
      significantly associated with excessive fetal weight. Shoulder dystocia,
      clavicular bone fracture and brachial palsy were more frequent in group of
      newborns with birth weight over 4500 g. The frequency of brachial dystocia and
      its complications (clavicular bone fracture and Erb's brachial palsy) were
      significantly connected with the use of VE. CONCLUSIONS: Significant increase in
      the frequency of perinatal complications in foetuses with birth weight over 4500
      g indicates the necessity of considering caesarean section as a favourable mode
      of delivery.

PMID- 17017477
TI  - [Usefulness of detecting cancer procoagulant activity and thyrotropic hormone
      concentration in the differentiation of tumor-like changes in the thyroid].
AB  - Epidemiological studies have shown the increased incidence of malignant cancer of
      the thyroid gland observed in the last decade. This increase is connected with
      the elevated number of benign tumor-like/tuberous changes in the thyroid gland.
      Since it is difficult to differentiate diagnostically this pathology, it would be
      justified to search for biochemical markers which can help to confirm this
      change. The aim of our study was to evaluate the usefulness of detecting cancer
      procoagulant activity (CP) and thyrotropic hormone concentration (TSH) in the
      differentiation of tumor-like changes in the thyroid gland. The study included 15
      patients (12 women and 3 men) with adenoma glandulae thyreoideae or nodular
      changes in the character of struma nodosa hyperplastica and 12 patients (11 women
      and 1 man) with carcinoma glandulae thyreoideae. A control group consisted of 12
      healthy people (5 women and 7 men). CP activity was determined in the serum by
      the coagulation method according to Gordon and Benson and it was expressed as the
      coagulation time in seconds (s). TSH concentration was measured by the
      immunoenzymatic method (MEIA) using an analyzer of Axsym (Abbott) and was
      expressed in microU/ml. The results of our study indicate that the determination
      of CP activity can be used in the differential diagnosis of tumor-like changes of
      the thyroid gland. The concentration ofTSH was within the normal values, despite
      statistically different mean values between particular groups that results from
      the fact that patients qualified to surgery were in the state of euthyreosis.

PMID- 17017478
TI  - [Cementless total hip arthroplasty--results of 8-year follow-up study].
AB  - The subjects of the clinical examinations were 382 patients who from 1994 to 1999
      were treated with the method of total cementless arthroplasty. The observation
      time ranged from 3 to 8 years. In the examined group the secondary cause of
      degenerative changes was identified in 210 (55%) patients. In the remaining 172
      cases (45%) the primary cause of degenerative changes in the hip was diagnosed.
      Four types of cementless endoprostheses, varied in their construction, structure
      of their surfaces and material they were made of, were used to carry out the
      postoperative treatment of the degenerative changes in the hip: Antega,
      Zweymuller SL PLUS (Endoprosthetic) or Alloclasic type of stem, GSS-CL and PM
      Plasmapore. The findings of the clinical investigation made it possible to
      determine the probability of surviving of an endoprosthesis up to the 8th year
      after an operation depending on a type of implanted stem, which according to
      Kaplan-Meier's method, amounted to 0.9603. The results of Harris scale evaluation
      of the function of the operated joints demonstrated the existence of the
      relationship between the function and the course of bone osteointegration and
      growth process. The detailed analysis of the X-ray examinations, and especially
      of the roentgenometric ones, taking into account stability of the endoprosthesis
      stem enabled to distinguish two stages of the clinical and roentgenological
      changes: the early stage (up to 6 months after an operation) characterised by
      settling and micromotions of the stem and the late stage (starting 6-9 months
      after an operation) with slowly gradual increasing of the function and holding
      back of stem settling.

PMID- 17017479
TI  - [Shotgun injuries--epidemiological and clinical aspects].
AB  - Shotgun injuries constitute an increasing surgical problem as they frequently
      lead to severe trauma disease and even to death. These injuries are mainly
      diagnosed in young people and are localized in limbs. Human life is in danger in
      case of shotgun injuries of the head (CNS), abdominal and thoracic cavities.
      Prognosis is worse in multiple shotgun lesions. The dominating cause of death in
      shotgun victims is hemorrhagic shock. Patient's life is potentially in a real
      danger and necessitates precise diagnostic and therapeutic management in the
      early stages following shotgun trauma, in the operating room and in the
      postoperative phase.

PMID- 17017480
TI  - [Influence of age of patients with atrial fibrillation on left atrium function].
AB  - Frequency of occurrence of atrial fibrillation (FA) increases with age. In the
      elderly this arrhythmia might influence the enlargement and function of left
      atrium (LA) and its appendage (LAA). The aim of this study was to assess the
      association between age of patients and selected echocardiographic parameters
      concerning left atrium. MATERIAL AND METHODS: 120 consecutive patients (52 women
      and 68 men) with FA were studied 36-89 years old (mean 68.7 +/- 10.9). Patients
      were divided into two groups using a cut-off value age of 70 years. Older than 70
      years were 64 patients, whereas below this age were 56 persons. Duration time of
      arrhythmia did not differ significantly between studied groups. In all patients
      transthoracic (TTE) and transoesophageal (TEE) echocardiography were performed to
      assess selected echocardiographic parameters concerning left atrium (LA) and its
      appendage (LAA). During TTE were measured: LA maximal diameter in M-mode (LAmax),
      LA transversal diameter in 4-CH (LAtrans), LA longitudinal diameter in 4-CH
      (LAlong), LA circulum in 4-CH (LAcirc), LA area in 4-CH (LAarea). Consequently
      TEE was done to assess LAA transversal diameter (LAAtrans), LAA longitudinal
      diameter (LAAlong), LAA circulum (LAAcirc), LAA area (LAAarea), spontaneous
      echocardiographic contrast (SEC), thrombus (THR), maximal LAA outflow velocity
      (LAAF), maximal LAA inflow velocity (LAAB), integral of LAA outflow velocity
      (LAAFintg) and integral of LAA inflow velocity (LAABintg). RESULTS: LAmax (4.91
      +/- 0.61 vs. 4.22 +/- 0.49), LAtrans (4.75 +/- 0.71 vs. 4.11 +/- 0.44) and LAarea
      (31.85 +/- 6.9 vs. 27.51 +/- 6.54) were significantly greater in older patients
      compared to those below 70 years old. LAlong, LAcirc, LAarea, LAA trans, LAAlong,
      LAAcirc did not differ between studied groups. Thrombi in LAA were detected
      rarely in study population and were found often in older patients (in 2 vs. 6
      patients). In almost 2/3 older patients SEC in LAA was visualized, which was
      markedly frequent when compared to younger group. In older patients parameters
      characterizing LAA function had significantly lower values than in younger
      patients (LAAF respectively 19.8 +/- 9.16 vs. 28.57 +/- 10.7, LAAB respectively
      21.6 +/- 8.12 vs. 31.81 +/- 10.88). CONCLUSIONS: In patients with atrial
      fibrillation left atrium and its appendage diameters are greater in the elderly.
      Left atrium appendage function is more deteriorated in older patients with atrial
      fibrillation. During atrial fibrillation thrombus formation and appearance of
      spontaneous echocardiographic contrast is more often in the elderly.

PMID- 17017481
TI  - [Anorexia nervosa in boys and men].
AB  - Anorexia nervosa (AN) is thought to appear predominantly in girls and young
      women. Twenty years ago the incidence of AN was considered as 1 boy to 10-15
      girls. Recent data suggest that the girls to boys rate is 4:1. The most
      frequently AN in boys begins during puberty. Boys and young men reluctantly apply
      for help to medical professionals trying to hide their symptoms. The diagnosis of
      AN is established and the treatment is being performed only when they suffer from
      a marked loss of weight or a severe depression with suicidal thoughts. We report
      seven male patients with AN and review the differences in a course of this
      disease between male and female patients.

PMID- 17017482
TI  - [Adults celiac disease--the tip of the iceberg].
AB  - In recent years the clinical course of celiac disease (CD; gluten enteropathy)
      has changed. It has been diagnosed more and more frequently in adults. Celiac
      disease in adults may manifest itself as active, silent, latent and late onset.
      To confirm the diagnosis of CD the most important is the result of jejunal mucosa
      biopsy and the presence of anti-endomysium, anti-reticuline and/or anti-tissue
      transglutaminase IgA antibodies in serum. All the patients with CD should be
      recommended a gluten free diet. In some cases, resistant to gluten free diet, the
      immunosuppressive therapy may be taken into consideration.

PMID- 17017483
TI  - [Is hyperuricemia a cardiovascular risk factor?].
AB  - The association of elevated serum uric acid (hyperuricemia, gout) with the
      presence of classical coronary risk factors and coronary artery disease (CAD) or
      myocardial infarction (MI) has been analysed in many epidemiological studies.
      Numerous studies have revealed that hypertension, high body mass index (BMI),
      lipid disorders (especially raised triglycerides--TG level and low high dense
      lipoprotein cholesterol HDL-C level), increased creatinine or insulin levels have
      caused hyperuricemia. No association has been observed between hyperuricemia and
      diabetes type 2 and uricemia and glicemia. But in some studies the relationship
      between cholesterol and uric acid levels has been not confirmed. Hyperuricemia
      has been observed in patients with non-treated hypertension. Gout has often
      occurred with typical disorders for the metabolic syndrome X. Significant
      correlation of the serum uric level and the CAD presence and severity of coronary
      atherosclerosis confirmed by coronary angiography has been observed in women.
      Hyperuricemia has also indirect influence on progress of CAD by physical activity
      restriction, what causes sedentary mode of life and lead to obesity. Obesity is a
      known risk factor diabetes, lipid disorders and hypertension. To recapitulate, it
      is a matter of controversy as to whether uric acid is an independent
      cardiovascular risk factor or rather it only represents reinforcement of typical
      risk factor.

PMID- 17017484
TI  - [The role of permanent pacing in atrial fibrillation].
AB  - Nowadays permanent pacing of the heart helps patients not only with pathological
      bradycardia or asystole in the tract of the AV blocks (AVB) and sick sinus
      syndrome (SSS), but is also valuable in the prevention of atrial fibrillation
      (AF) as well as the stabilization of the rhythm in chronic AF. For this reason
      patients with AF are often candidates for implantation of a cardiac pacemaker.
      The basic problem for doctor qualifying patients for pacemaker implantation with
      AF is the choice of a suitable type of pacing. However, this is not the only
      problem. New possibilities in the tract of solid and very quick progress in the
      field of pacing have appeared but there are also new doubts. The present
      publication presents the possibilities of utilization of types of pacing in this
      field including the newest solutions (antyarrhythmic algorithms) along with the
      role of placement of stimulation (dual site right ventricular pacing). Hybrid
      therapy is also described as the only alternative in special circumstances. All
      these methods were supported by the data from the latest trial.

PMID- 17017485
TI  - [Achievement of endodontics at the edge of the century].
AB  - Endodontics is the branch of dentistry which deals with dental pulp pathology and
      treatment of root canals. There has been noted a significant improvement in this
      discipline recently, which has made a substantial increase in therapeutical
      efficiency and made dentists' work easier. It was possible due to dynamic
      development of new material technologies and clinical procedures. Aim of this
      paper was to present the current state of knowledge in endodontics. The most
      important achievements were especially stressed. Among the most important for
      development of present endodontics there are: new methods of canal length
      estimation, modem methods of visualization, nickel titanium rotary
      instrumentation, numerous gutta-percha obturation systems and also more
      biocompatible obturation materials.

PMID- 17017486
TI  - [Hormonal replacement therapy and selective estrogen receptor modulators in
      prevention of cardiovascular disease].
AB  - Postmenopausal women are at higher risk of cardiovascular disease because of
      increased prevalence of major coronary artery disease risk factors. The
      protective activity on cardiovascular system of estrogen was postulated. The data
      from many studies indicate favourable effect of estrogen replacement therapy.
      However prospective, randomized clinical trials have not proved protective
      influence of hormonal replacement therapy (HRT) on cardiovascular system.
      Moreover it was found to increased the risk of cardiovascular disease events.
      This article presents mechanism of estrogens activity and results of major
      clinical trials concerning hormonal replacement therapy. Activity of selective
      estrogen receptor modulators (SERMs) was also described.

PMID- 17017487
TI  - [Prophylactic and therapeutic application of thiamine (vitamin B1)--a new point
      of view].
AB  - Usefulness and application of vitamin B1 (thiamine) and it's derivatives
      (benfotiamine, sulfotiamine) in some environmental diseases like congestive heart
      failure and diabetes is described. Possibility of its use in geriatry and in pain
      associated diseases is also analysed. Concise description of the role of thiamine
      in the human organism, its content in some food products and results of this
      vitamin deficiency are also presented.

PMID- 17017488
TI  - [Propranolol--a place in the modern therapy].
AB  - The discovery of propranolol in 1964 and its introducing to the clinical practice
      has been essential for the progress in the diagnostics and therapy of
      cardiovascular diseases. Indications for the use ofpropranolol are numerous.
      Propranolol has shown clinical usefulness in the treatment of angina pectoris,
      hypertension, cardiac arrhythmias, hyperthrophic obstructive cardiomyopathy,
      mitral stenosis, and pheochromocytoma. It has proved efficacy in the treatment
      ofhyperthyroidism, porphyria, cirrhosis, migraine and in the therapy of many
      neuropsychiatric disorders. The article presents a review of the actual clinical
      applications of propranolol.

PMID- 17017489
TI  - [Diagnostic and therapeutic problems of scleroderma].
AB  - Scleroderma is the autoimmunologic disease with induration and fibrosis of the
      skin, subcutaneous tissue; sometimes refers to muscles, bones and other internal
      organs. Pathogenesis of morphea is still unknown. There are two main types of
      scleroderma: the first type is related only to the skin (localized scleroderma-
      morphea), while the second is connected with fibrosis and induration of the skin,
      lungs, heart and other organs (systemic sclerosis). There are various clinical
      forms of scleroderma circumscripta: linear scleroderma (the most frequent in
      children), morphea en plaque, generalized morphea, nodular and keloidea like,
      morphea guttata, scleroderma circumscripta with blisters on the surface-bullous
      morphea. Morphea profunda is the most severe type of scleroderma localized on the
      skin. Although the diagnosis of morphea is not so difficult, the treatment is
      problematic and not very effective. It is very important to initiate the proper
      treatment as soon as possible. There are three main ways of morphea treatment:
      medication (receiving local or per os), physical methods (for example
      phototherapy) and balneotherapy or climatic treatment.

PMID- 17017490
TI  - [Nasal provocation tests in the diagnosis of allergic rhinitis].
AB  - Allergic rhinitis is a frequent immunological disease affecting about 10-25% of
      the total population. The pathogenesis of allergic rhinitis is presumed to
      involve an IgE-mediated mechanism. Careful patient history, together with the
      skin prick test or RAST, usually allows an easy diagnosis of allergic rhinitis.
      In other cases it may be necessary to confirm diagnosis by the nasal provocation
      test. Different methods of provocation and measurement of nasal responses have
      been used in recent years. Scoring of the severity of clinical symptoms is too
      subjective to be clinically useful and should therefore be supplemented by one of
      the objective measurement techniques, such as anterior rhinomanometry. Additional
      analysis of nasal cytologic findings and determination of biomarkers in nasal
      secretions can be a critical tool in the evaluation of pathophisiology of
      allergic rhinitis. We critically discuss indications and contraindications for
      nasal challenges and review current techniques of provocation. We also provide
      various methods of assessment of nasal responses. The included examples of nasal
      provocation tests protocols may be helpful in introducing nasal provocation tests
      into everyday clinical practice.

PMID- 17017491
TI  - [The treatment of obesity-related hypertension].
AB  - The increase in the prevalence of obesity is associated with an increased risk of
      the development of cardiovascular and renal diseases. Extensive epidemiological
      studies have demonstrated a relation between the body weight rate and the blood
      pressure, indicating obesity as one of the factors in hypertension development.
      Some classes of antihypertensive drugs have potentially adverse effects on some
      of the metabolic abnormalities that link obesity and hypertension. At the same
      time, there is no scientific evidence indicating a more efficient group of drugs
      in the pharmacological management of the obese-related hypertension, therefore
      the drug treatment choice is based on experience and observations. Based on a
      particular mechanism leading to the development of hypertension in the obese
      individuals, the treatment includes the weight reduction associated with the
      pharmacological management which decreases the risks of both hypertension and
      obesity.

PMID- 17017492
TI  - [Contemporary views of the role of HPV infection in oncogenesis in cervical
      cancer].
AB  - Cervical cancer is the second most common cancer of the woman worldwide.
      Infection with some genotypes of human papillomavirus (HPV) is the most important
      risk factor associated to cervical cancer, particularly HPV type 16 and 18 and
      potentially 31 and 45. Till now specific treatment or vaccination is not
      available but recently published results can be the first step to produce
      specific vaccination and reduce the number of cervical cancer. HPV has an
      influence on oncogenesis, but there are also mechanisms not depending on HPV
      infection. Recently published Institute Pasteur' data concerning the HPV genom
      may be the first step to produce specific vaccination.

PMID- 17017493
TI  - [Epilepsy in the elderly people].
AB  - Recently an increasing number of cases of epilepsy revealed after 60 years of age
      have been noted. Epilepsy in the elderly may cause some diagnostic and
      therapeutic difficulties, it constitutes social problems as well. The authors
      present current epidemiological data, discuss pathogenesis of seizures, clinical
      course and prognosis, rules of differential diagnosis and treatment, highlighting
      specific features of the disease in this age group.

PMID- 17017494
TI  - [Erythema nodosum in a child with salmonellosis].
AB  - We report a case of 4-years-old girl who suffered one episode of clinically
      typical erythema nodosum and arthralgia of short duration. Stool culture showed
      growth of Salmonella enteritidis. Levels of serum anti-Salmonella antibodies and
      immunocomplexes lowered during resolution of skin nodules. Erythema nodosum
      probably results from the formation of immunocomplexes and their deposition in
      and around blood vessels of the skin. Salmonellosis should be considered in
      patients presenting with erythema nodosum. Routine stool culture might provide an
      important diagnostic clue.

PMID- 17017495
TI  - [Encapsulating peritoneal sclerosis--a serious complication of peritoneal
      dialysis with not characteristic symptoms].
AB  - Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients on
      peritoneal dialysis (PD). We report the case of a 45 years old woman who
      developed EPS five years after being placed on CAPD. We did not observe any
      typical abdominal symptoms. Recurrent cloudy and blood stained dialysate as well
      as deterioration of adequacy were noted few month before histological
      verification. The results of radiological findings did not allow for precise
      diagnosis. A patient had undergone an operation because of massive bleeding to
      the renal cyst during which a completely walled up peritoneal cavity was revealed
      (the bowel loops were cocooned in thickened peritoneum). Histological examination
      of peritoneal specimen confirmed the diagnosis. The patient died due to
      inflammatory and bleeding complications one month after an operation.

PMID- 17017496
TI  - [Metastasis to brain from rectal cancer as the first manifestation of
      neoplasmatic disease].
AB  - Cerebral metastases from colorectal cancer are uncommon. They are usually a late
      manifestation of the neoplasmatic disease. The symptoms aren't always typical. We
      report the case of 52-year-old woman in whom the first manifestation of the
      disease was metastasis to brain.

PMID- 17017497
TI  - [Asthma as a mask of other respiratory diseases].
AB  - Everyday clinical practice reveals both cases of asthma with non-typical symptoms
      as well as pseudo-asthmatic syndromes with symptoms typical for asthma.
      Bronchofiberoscopy is a diagnostic method which may help to overcome many
      diagnostic problems. Although it is a safe procedure, an increased risk of severe
      bronchoconstriction exists in patients with asthma. The fear of this complication
      may cause late diagnosis of some asthma-mimicking diseases and may delay the
      proper treatment. In the present paper we describe two cases showing the
      possibility of making diagnostic mistakes, and especially illustrating the role
      ofbronchoscopy in differential diagnosis of bronchial asthma. The authors remind
      specific indications for this examination in patients with asthma or those
      presenting asthma-like symptoms. Safety precautions have been also recollected.
      If safety rules are met, severe bronchoconstriction in patients with bronchial
      hyperreactivity can be avoided.

PMID- 17017498
TI  - [Anaemia from religious reasons as a distant effect of husband's alcoholism].
AB  - Chronic nutrition deficiencies, economic or cultural in their nature are one of
      the most often reason ofanaemia. From the other hand various diet restrictions
      may lead to different nutrition deficiencies. The occurrence of anaemia caused by
      diet restrictions is relatively rare among Catholics in Poland. We present a case
      of 51 years old woman with severe anaemia (Hgb 2.48 mmol/l), occasionally
      diagnosed. Anaemia occurred 20 years after she took a pledge never to eat meat.
      The aim of her oath was the begging for grace and quitting alcoholism by her
      husband, a habitual alcoholic. The iron and vitamin B12 supplementation led to
      quick improvement of hematological parameters.

PMID- 17017499
TI  - [Sigmoido-vesical fistula as a cause of recurrent urinary tract infections].
AB  - The authors describe a case of sigmoido-vesical fistula in 64 years old woman.
      The fistula probably developed as a result of complications of sigmoidal
      diverticulitis. The main clinical manifestation were symptoms of recurrent
      urinary tract infections and pneumaturia. For the diagnosis of the fistula
      different methods such as urography, cystography, ultrasonographic examination,
      colonoscopy, bacteriological urine analysis and laboratory investigations were
      used. The patient was qualified to surgical treatment. One-stage operation
      performed appeared successful.

PMID- 17017500
TI  - [Comment to the study: Metastasis to brain from rectal cancer as the first
      manifestation of neoplasmatic disease].

PMID- 17017501
TI  - [Idiopathic scholiosis--etiopathogenesis, biomechanical influence, new
      classification, three etiopathogenesis groups, new rehabilitation treatment;
      neoprophylaxis].

PMID- 17017502
TI  - The discovery of dopamine deficiency in the parkinsonian brain.
AB  - This article gives a short historical account of the events and circumstances
      that led to the discovery of the occurrence of dopamine (DA) in the brain and its
      deficiency in Parkinson's disease (PD). Some important consequences, for both the
      basic science and the patient, of the work on DA in the PD brain are also
      highlighted.

PMID- 17017503
TI  - Synchronizing activity of basal ganglia and pathophysiology of Parkinson's
      disease.
AB  - Early physiological studies emphasized changes in the discharge rate of basal
      ganglia in the pathophysiology of Parkinson's disease (PD), whereas recent
      studies stressed the role of the abnormal oscillatory activity and neuronal
      synchronization of pallidal cells. However, human observations cast doubt on the
      synchronization hypothesis since increased synchronization may be an epi
      phenomenon of the tremor or of independent oscillators with similar frequency.
      Here, we show that modern actor/ critic models of the basal ganglia predict the
      emergence of synchronized activity in PD and that significant non-oscillatory and
      oscillatory correlations are found in MPTP primates. We conclude that the normal
      fluctuation of basal ganglia dopamine levels combined with local cortico-striatal
      learning rules lead to noncorrelated activity in the pallidum. Dopamine
      depletion, as in PD, results in correlated pallidal activity, and reduced
      information capacity. We therefore suggest that future deep brain stimulation
      (DBS) algorithms may be improved by desynchronizing pallidal activity.

PMID- 17017504
TI  - Basal ganglia discharge abnormalities in Parkinson's disease.
AB  - In the traditional model of the pathophysiology of parkinsonism, parkinsonian
      motor signs are viewed as the result of changes in discharge rates in the basal
      ganglia. However, not all experimental findings can be explained by rate changes
      alone, and changes in discharge patterns in these nuclei are increasingly
      emphasized as pathophysiologically important, including changes in burst
      discharges, in synchrony, and in oscillatory activity. This brief review
      highlights the pathophysiologic relevance of these rate and pattern changes in
      the pathophysiology of parkinsonism.

PMID- 17017505
TI  - Bad oscillations in Parkinson's disease.
AB  - Recordings in humans as a result of functional neurosurgery have revealed a
      tendency for basal ganglia neurons to oscillate and synchronise their activity,
      giving rise to a rhythmic population activity, manifest as oscillatory local
      field potentials. The most important activity is synchronised oscillation in the
      beta band (13-30 Hz), which has been picked up at various sites within the basal
      ganglia-cortical loop in PD. Dopaminergic medication and movement suppress this
      activity, with the timing and degree of suppression closely correlating with
      behavioural performance. Accordingly synchronisation in the beta band has been
      hypothesised to be essentially antikinetic in nature and pathophysiologically
      relevant to bradykinesia.

PMID- 17017506
TI  - Cortical muscle coupling in Parkinson's disease (PD) bradykinesia.
AB  - OBJECTIVES: To determine if novel methods establishing patterns in EEG-EMG
      coupling can infer subcortical influences on the motor cortex, and the
      relationship between these subcortical rhythms and bradykinesia. BACKGROUND:
      Previous work has suggested that bradykinesia may be a result of inappropriate
      oscillatory drive to the muscles. Typically, the signal processing method of
      coherence is used to infer coupling between a single channel of EEG and a single
      channel of rectified EMG, which demonstrates 2 peaks during sustained
      contraction: one, approximately 10 Hz, which is pathologically increased in PD,
      and a approximately 30 Hz peak which is decreased in PD, and influenced by
      pharmacological manipulation of GABAA receptors in normal subjects. MATERIALS AND
      METHODS: We employed a novel multiperiodic squeezing paradigm which also required
      simultaneous movements. Seven PD subjects (on and off L-Dopa) and five normal
      subjects were recruited. Extent of bradykinesia was inferred by reduced relative
      performance of the higher frequencies of the squeezing paradigm and UPDRS scores.
      We employed Independent Component Analysis (ICA) and Empirical Mode Decomposition
      (EMD) to determine EEG/EMG coupling. RESULTS: Corticomuscular coupling was
      detected during the continually changing force levels. Different components
      included those over the primary motor cortex (ipsilaterally and contralaterally)
      and over the midline. Subjects with greater bradykinesia had a tendency towards
      increased approximately 10 Hz coupling and reduced approximately 30 Hz coupling
      that was erratically reversed with L-dopa. CONCLUSIONS: These results suggest
      that lower approximately 10 Hz peak may represent pathological oscillations
      within the basal ganglia which may be a contributing factor to bradykinesia in
      PD.

PMID- 17017508
TI  - The engrailed transcription factors and the mesencephalic dopaminergic neurons.
AB  - The engrailed genes belong to a large family of homeobox transcription factors.
      They are found throughout the animal kingdom, are highly conserved in the DNA
      binding domain and have been investigated for more than half a century. In the
      murine genome, two engrailed genes exist, called Engrailed-1 and Engrailed-2.
      Here, we summarize the properties of the engrailed genes and their functions,
      such as conserved structures, cellular localisation, secretion and
      internalisation, transcription factor activity, potential target genes and review
      their role in the development of mesencephalic dopaminergic neurons. During early
      development, they take part in the regionalization event, which specifies the
      neuroepithelium that provides the precursor cells of the mesencephalic
      dopaminergic neurons with the necessary signals for their induction. Later in the
      post-mitotic neurons, the two transcription factors participate in their
      specification and are cell-autonomously required for their survival.

PMID- 17017507
TI  - GDNF as a candidate striatal target-derived neurotrophic factor for the
      development of substantia nigra dopamine neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been known for many years
      to protect and restore dopamine neurons of the substantia nigra (SN) in lesion
      models of parkinsonism, but much less has been known of its normal physiologic
      role. We have found that GDNF injected into the striatum postnatally suppresses
      naturally-occurring cell death in SN dopamine neurons, and neutralizing
      antibodies augments it. Neutralizing antibodies augment cell death during the
      first phase, which occurs during the first postnatal week, but not during the
      second phase in the second week. To further explore the possible neurotrophic
      role of GDNF, we created double transgenic mice which overexpress GDNF
      exclusively in the target regions of mesencephalic neurons, particularly the
      striatum. As anticipated for a limiting, target-derived factor, this resulted in
      an increased surviving number of SN dopamine neurons after the first phase of
      cell death. However, this increase did not persist into adulthood. We conclude
      that GDNF is the leading candidate for a target-derived neurotrophic factor for
      SN dopamine neurons during the first phase of cell death, but that other factors
      must play an essential role in later development.

PMID- 17017509
TI  - The role of Pitx3 in survival of midbrain dopaminergic neurons.
AB  - Dopamine belongs to the most intensively studied neurotransmitters of the brain,
      because of its implications in psychiatric and neurological disorders. Although,
      clinical relevance of midbrain dopaminergic (mDA) neurons is well recognized and
      dopaminergic dysfunction may have a genetic component, the genetic cascades
      underlying developmental processes are still largely unknown. With the advances
      in molecular biology, mDA neurons and their involvement in psychiatric and
      neurological disorders are now subject of studies that aim to delineate the
      fundamental neurobiology of these neurons. These studies are concerned with
      developmental processes, cell-specific gene expression and regulation, molecular
      pharmacology, and genetic association of dopamine-related genes and mDA
      associated disorders. Several transcription factors implicated in the post
      mitotic mDA development, including Nurr1, Lmx1b, Pitx3, and En1/En2 have
      contributed to the understanding of how mDA neurons are generated in vivo.
      Furthermore, these studies provide insights into new strategies for future
      therapies of Parkinson's Disease (PD) using stem cells for engineering DA neurons
      in vitro. Here, we will discuss the role of Pitx3 in molecular mechanisms
      involved in the regional specification, neuronal specification and
      differentiation of mDA neurons.

PMID- 17017510
TI  - Genetic analysis of dopaminergic system development in zebrafish.
AB  - Zebrafish have become an important model organism to study the genetic control of
      vertebrate nervous system development. Here, we present an overview on the
      formation of dopaminergic neuronal groups in zebrafish and compare the positions
      of DA neurons in fish and mammals using the neuromere model of the vertebrate
      brain. Based on mutant analysis, we evaluate the role of several signaling
      pathways in catecholaminergic neuron specification. We further discuss the
      prospect of identifying novel genes involved in dopaminergic development through
      forward genetics mutagenesis screens.

PMID- 17017511
TI  - Striatal plasticity in parkinsonism: dystrophic changes in medium spiny neurons
      and progression in Parkinson's disease.
AB  - Striatal dopamine loss in Parkinson's Disease (PD) sets into play a variety of
      compensatory responses to help counter dopamine depletion. Most of these changes
      involve surviving dopamine neurons, but there are also changes in striatal medium
      spiny neurons (MSNs), which are the major target of dopamine axons. Among these
      changes are decreases in MSN dendritic length and spine density, which may dampen
      excessive corticostriatal glutamatergic drive onto MSNs that occurs secondary to
      dopamine loss. An increasing knowledge of dendritic changes in PD suggests
      strategies for tracking progressive worsening of symptoms and is opening new
      ideas on novel therapeutic strategies for PD.

PMID- 17017512
TI  - The nigrostriatal DA pathway and Parkinson's disease.
AB  - The discovery of the nigrostriatal DA system in the rat was made possible by the
      highly specific and sensitive histochemical fluorescence method of Falck and
      Hillarp in combinations with electrolytic lesions in the substantia nigra and
      removal of major parts of the neostriatum. Recent work on DA neuron evolution
      shows that in the Bottlenose Dolphin the normal DA cell groups of the substantia
      nigra are very cell sparse, while there is a substantial expansion of the A9
      medial and A10 lateral subdivisions forming an impressive "ventral wing" in the
      posterior substantia nigra. The nigrostriatal DA pathway mainly operates via
      Volume Transmission. Thus, DA diffuses along concentration gradients in the ECF
      to reach target cells with high affinity DA receptors. A novel feature of the DA
      receptor subtypes is their physical interaction in the plasma membrane of
      striatal neurons forming receptor mosaics (RM) with the existence of two types of
      RM. The "functional decoding unit" for DA is not the single receptor, but rather
      the RM that may affect not only the integration of signals in the DA neurons but
      also their trophic conditions. In 1991 A2A receptor antagonists were indicated to
      represent novel antiparkinsonian drugs based on the existence of A2A/D2 receptor
      receptor interactions and here P2X receptor antagonists are postulated to be
      neuroprotective drugs in treatment of Parkinson's Disease.

PMID- 17017513
TI  - Relationship between axonal collateralization and neuronal degeneration in basal
      ganglia.
AB  - In this paper we evaluate the hypothesis of a possible link between the degree of
      axonal collateralization of neurons located within the different components of
      basal ganglia and the vulnerability of these neurons to neurodegenerative or
      neurotoxic events. Our results stemmed from single-cell labeling experiments in
      rodents and primates, immunohistochemical study of the dopaminergic nigrostriatal
      pathway in parkinsonian monkeys, and immunocytological analysis of the human
      striatum in normal individuals and in patients with Huntington's disease. Our
      results indicate that projection neurons within virtually all basal ganglia
      components are endowed with a widespread and highly collateralized axon that
      yields a fixed number of terminals. Such a high degree of axonal
      collateralization allows exquisitely precise interactions between the various
      basal ganglia nuclei. However, the maintenance of this unique morphological trait
      implies high-energy consumption and renders basal ganglia neurons highly
      vulnerable to neurodegenerative, metabolic or neurotoxic insults.

PMID- 17017514
TI  - Pathology associated with sporadic Parkinson's disease--where does it end?
AB  - Parkinson's disease (PD) is a multisystem disorder in which predisposed neuronal
      types in specific regions of the human peripheral, enteric, and central nervous
      systems become progressively involved. A staging procedure for the PD-related
      inclusion body pathology (i.e., Lewy neurites and Lewy bodies) in the brain
      proposes that the pathological process begins at two sites and progresses in a
      topographically predictable sequence in 6 stages. During stages 1-2, the
      inclusion body pathology remains confined to the medulla oblongata, pontine
      tegmentum, and anterior olfactory structures. In stages 3-4, the basal mid- and
      forebrain become the focus of the pathology and the illness reaches its
      symptomatic phase. In the final stages 5-6, the pathological process is seen in
      the association areas and primary fields of the neocortex. To date, we have
      staged a total of 301 autopsy cases, including 106 cases with incidental
      pathology and 176 clinically diagnosed PD cases. In addition, 163 age-matched
      controls were examined. 19 of the 301 cases with PD-related pathology displayed a
      pathological distribution pattern of Lewy neurites and Lewy bodies that diverged
      from the staging scheme described above. In these cases, olfactory structures and
      the amygdala were predominantly involved in the virtual absence of brain stem
      pathology. Most of the divergent cases (17/19) had advanced concomitant
      Alzheimer's disease-related neurofibrillary changes (stages IV-VI).

PMID- 17017515
TI  - Critical appraisal of brain pathology staging related to presymptomatic and
      symptomatic cases of sporadic Parkinson's disease.
AB  - Clinical Parkinson's disease (PD) is a well-characterised syndrome that benefits
      significantly from dopamine replacement therapies. A staging procedure for
      sporadic PD pathology was developed by Braak et al. assuming that the abnormal
      deposition of alpha-synuclein indicates the intracellular process responsible for
      clinical PD. This paradigm has merit in corralling patients with similar cellular
      mechanisms together and determining the potential sequence of events that may
      herald the clinical syndrome. Progressive pathological stages were identified--1)
      preclinical (stages 1-2), 2) early (stages 3-4, 35% with clinical PD) and 3) late
      (stages 5-6, 86% with clinical PD). However, preclinical versus early versus late
      stage cases should on average be progressively older at the time of sampling, a
      feature not observed in the cohort analysed. In this cohort preclinical cases
      would have developed extremely late-onset PD compared with the other types of
      cases analysed. While the staging scheme is a valuable concept, further
      development is required.

PMID- 17017516
TI  - A short overview on the role of alpha-synuclein and proteasome in experimental
      models of Parkinson's disease.
AB  - The Ubiquitin Proteasome System is a multi-enzymatic pathway which degrades
      polyubiquinated soluble cytoplasmic proteins. This biochemical machinery is
      impaired both in sporadic and inherited forms of Parkinsonism. In the present
      paper we focus on the role of the pre-synaptic protein alpha-synuclein in
      altering the proteasom based on the results emerging from experimental models
      showing a mechanistic chain of events between altered alpha-synuclein, proteasome
      impairment and formation of neuronal inclusions and catecholamine cell death.

PMID- 17017517
TI  - The role of protein aggregates in neuronal pathology: guilty, innocent, or just
      trying to help?
AB  - Protein aggregates such as Lewy bodies have done much for the scientists in the
      field of neurodegenerative diseases: They have highlighted the affected cell
      populations and they have trapped the mutant disease protein. Instead of a good
      reputation, however, protein aggregates have received incriminations, because
      they are consistently seen at the site of crime. Reviewing the arguments, crucial
      evidence has become known that (a) the specific neuronal pathology precedes the
      appearance of protein aggregates in mouse models of disease, (b) the
      neurodegenerative disease in patients occurs with comparable severity when
      visible protein aggregates remain absent, (c) the neurotoxicity in vitro is best
      reproduced by oligomers, not polymers of the mutant disease protein. Is it
      feasible that protein aggregates are inert byproducts of the disease protein
      malconformation, or that they even represent beneficial cellular efforts to
      sequestrate the soluble toxic disease protein, together with normal or aberrant
      interactor proteins? Whatever the answer will be, one positive role of protein
      aggregates seems clear: In contrast to earlier speculations that random
      cytoplasmic proteins are trapped within the aggregates, scientists now believe
      that the composition of the Lewy body reflects the network of interactions
      between crucial players in disease pathogenesis, such as the PARK1, PARK2 and
      PARK5 protein.

PMID- 17017518
TI  - New face of neuromelanin.
AB  - The massive, early and relatively circumscribed death of the dopaminergic neurons
      of the substantia nigra in Parkinson's disease has not yet been adequately
      explained. The characteristic feature of this brain region is the presence of
      neuromelanin pigment within the vulnerable neurons. We suggest that neuromelanin
      in the Parkinson's disease brain differs to that in the normal brain. The
      interaction of neuromelanin with iron has been shown to differ in the
      parkinsonian brain in a manner consistent with an increase in oxidative stress.
      Further, we suggest an interaction between the lipoprotein alpha-synuclein and
      lipidated neuromelanin contributes to the aggregation of this protein and cell
      death in Parkinson's disease. The available data suggest that the melaninisation
      of the dopaminergic neurons of the substantia nigra is a critical factor to
      explain the vulnerability of this brain region to early and massive degeneration
      in Parkinson's disease.

PMID- 17017519
TI  - The effect of neuromelanin on the proteasome activity in human dopaminergic SH
      SY5Y cells.
AB  - In Parkinson's disease (PD), the selective depletion of dopamine neurons in the
      substantia nigra, particular those containing neuromelanin (NM), is the
      characteristic pathological feature. The role of NM in the cell death of dopamine
      neurons has been considered either to be neurotoxic or neuroprotective, but the
      precise mechanism has never been elucidated. In human brain, NM is synthesized by
      polymerization of dopamine and relating quinones, to which bind heavy metals
      including iron. The effects of NM prepared from human brain were examined using
      human dopaminergic SH-SY5Y cells. It was found that NM inhibits 26S proteasome
      activity through generation of reactive oxygen and nitrogen species from
      mitochondria. The mitochondrial dysfunction was also induced by oxidative stress
      mediated by iron released from NM. NM accumulated in dopamine neurons in ageing
      may determine the selective vulnerability of dopamine neurons in PD.

PMID- 17017520
TI  - Potential sources of increased iron in the substantia nigra of parkinsonian
      patients.
AB  - Histopathological, biochemical and in vivo brain imaging techniques, such as
      magnetic resonance imaging and transcranial sonography, revealed a consistent
      increase of substantia nigra (SN) iron in Parkinson's disease (PD). Increased
      iron deposits in the SN may have genetic and non-genetic causes. There are
      several rare movement disorders associated with neurodegeneration, and genetic
      abnormalities in iron regulation resulting in iron deposition in the brain. Non
      genetic causes of increased SN iron may be the result of a disturbed or open
      blood-brain-barrier, local changes in the normal iron-regulatory systems,
      intraneuronal transportation of iron from iron-rich area into the SN and release
      of iron from intracellular iron storage molecules. Major iron stores are ferritin
      and haemosiderin in glial cells as well as neuromelanin in neurons. Age- and
      disease dependent overload of iron storage proteins may result in iron release
      upon reduction. Consequently, the low molecular weight chelatable iron complexes
      may trigger redox reactions leading to damage of biomolecules. Additionally, upon
      neurodegeneration there is strong microglial activation which can be another
      source of high iron concentrations in the brain.

PMID- 17017521
TI  - Iron and Friedreich ataxia.
AB  - Friedreich ataxia is due to insufficient levels of frataxin, a mitochondrial iron
      chaperone that shields this metal from reactive oxygen species (ROS) and renders
      it bioavailable as Fe II. Frataxin participates in the synthesis of iron-sulfur
      clusters (ISCs), cofactors of several enzymes, including mitochondrial and
      cytosolic aconitase, complexes I, II and III of the respiratory chain, and
      ferrochelatase. It also plays a role in the maintenance of ISCs, in particular
      for mitochondrial aconitase. A role of frataxin in heme synthesis has been
      postulated, but is controversial. Insufficient frataxin leads to deficit of ISC
      enzymes and energy deficit. Iron levels increase in mitochondria. Oxidative
      stress may result from respiratory chain dysfunction and from direct reaction
      between iron and ROS. Stress pathways are activated that may lead to apoptosis or
      other forms of cell death. The basis for the selective vulnerability of specific
      neurons, like sensory neurons, is still unknown.

PMID- 17017522
TI  - Nongenetic causes of Parkinson's disease.
AB  - Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by
      discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time,
      epidemiologic investigations have suggested risk factors, though their results do
      not establish causality. Pesticide exposure has been associated with increased
      risk in many studies. Other proposed risks include rural residence and certain
      occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal
      antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary
      lipid and milk consumption, high caloric intake, and head trauma may increase
      risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility
      and combinations of risk and protective factors likely all contribute. The
      combined research effort by epidemiologists, geneticists, and basic scientists
      will be needed to clarify the cause(s) of PD.

PMID- 17017523
TI  - Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae?
AB  - An abnormally frequent atypical levodopa-unresponsive, akinetic-rigid syndrome
      with some similarity to PSP was identified in the Caribbean island Guadeloupe,
      and was associated with the consumption of plants of the Annonacea family,
      especially Annona muricata (corossol, soursop) suggesting a possible toxic
      etiology. Annonaceae contain two groups of potential toxins, alkaloids and
      acetogenins. Both alkaloids and annonacin, the most abundant acetogenin, were
      toxic in vitro to dopaminergic and other neurons. However we have focused our
      work on annonacin for two reasons: (1) annonacin was toxic in nanomolar
      concentrations, whereas micromolar concentrations of the alkaloids were needed,
      (2) acetogenins are potent mitochondrial poisons, like other parkinsonism
      inducing compounds. We have also shown that high concentrations of annonacin are
      present in the fruit or aqueous extracts of the leaves of A. muricata, can cross
      the blood brain barrier since it was detected in brain parenchyma of rats treated
      chronically with the molecule, and induced neurodegeneration of basal ganglia in
      these animals, similar to that observed in atypical parkinsonism. These studies
      reinforce the concept that consumption of Annonaceae may contribute to the
      pathogenesis of atypical parkinsonism in Guadeloupe.

PMID- 17017524
TI  - CYP450, genetics and Parkinson's disease: gene x environment interactions hold
      the key.
AB  - The ecogenetic theory contends that most cases of Parkinson's disease (PD) result
      from the actions of environmental factors in genetically susceptible individuals
      on a background of normal ageing. This notion is supported by epidemiologic data;
      family history of PD and exposures to environmental toxins such as pesticides
      increase risk, while cigarette smoking reduces risk. As a result, polymorphic
      genes that code for metabolic enzymes have been considered as candidates for
      conferring differential risk for PD. Given their prominence in xenobiotic
      metabolism, the cytochrome P450 (CYP) genes have come under great scrutiny. The
      activity of CYP2D6 is largely determined by genetic variability and common
      sequence variants exist in human populations that lead to poor metaboliser (PM)
      phenotypes. These have been extensively studied as genetic risk factors for PD
      with inconsistent results. However, these studies have disregarded interactive
      effects (e.g. gene x environment interactions) despite the assertions of the
      ecogenetic theory. Data from our group and others suggest that the CYP2D6 PM
      genotype interacts with certain environmental factors such as pesticide exposure
      and cigarette smoking to confer differential risk for PD. Previous failure to
      consider such interactions might, in part, explain the inconsistencies observed
      in the CYP2D6 genetic risk-factor literature. Our data illustrate, using CYP2D6
      as an exemplar, that it is crucial to consider both genetic and environmental
      factors, and their interactions, in any examination of risk factors for PD.

PMID- 17017525
TI  - Unique cytochromes P450 in human brain: implication in disease pathogenesis.
AB  - Cytochromes P450 is a family of heme proteins that metabolize xenobiotics
      including drugs. Unique human brain cytochrome P450 enzymes metabolize
      xenobiotics including drugs to active/inactive metabolites through
      biotransformation pathways that are different from the well-characterized ones in
      liver. We have identified an alternate spliced functional transcript of CYP2D7
      containing partial inclusion of intron 6 in human brain but not in liver or
      kidney from the same individual. Genotyping revealed the presence of the frame
      shift mutation 138delT only in those subjects who expressed the brain variant
      CYP2D7, which metabolizes codeine exclusively to morphine unlike hepatic CYP2D6
      that metabolizes codeine to nor codeine and morphine. CYP1A1 bioactivates
      polycyclic aromatic hydrocarbons to reactive DNA binding metabolites and
      initiates carcinogenesis. We have identified a unique splice variant of CYP1A1
      having deletion of 87 bp of exon 6 which is present in human brain but not in
      liver of the same individual. We present evidence for the existence of
      biotransformation pathways in human brain that are dissimilar from known pathways
      in liver. Identification and characterization of novel CNS-specific P450 enzymes
      generated by alternate splicing of known genes or as yet unidentified genes may
      help predict consequences of exposure to xenobiotics including pesticides in the
      brain.

PMID- 17017526
TI  - Cytochrome P450 and Parkinson's disease: protective role of neuronal CYP 2E1 from
      MPTP toxicity.
AB  - Elucidation of the biochemical steps leading to the 1-Methyl-4-Phenyl-1,2,3,6
      Tetrahydropyridine (MPTP)-induced degeneration of the nigro-striatal dopamine
      (DA) pathway has provided new clues to the pathophysiology of Parkinson's Disease
      (PD). In line with the enhancement of MPTP toxicity by diethyldithiocarbamate
      (DDC), here we demonstrate how other CYP450 (2E1) inhibitors, such as diallyl
      sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective
      DA neuron degeneration in C57/bl mice. In order to provide direct evidence for
      this isozyme involvement, CYP 2E1 knockout mice were challenged with MPTP or the
      combined treatment. Here we show that these transgenic mice have a low
      sensitivity to MPTP alone, similarly to the wild type SVI, suggesting that it is
      likely that transgenic mice compensate for the missing enzyme. However, in these
      CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP
      toxicity; this enhancement is instead regularly present in the SVI control
      animals. This study indicates that the occurrence of CYP 2E1 in C57/bl mouse
      brain is relevant for MPTP toxicity, and suggests that this isozyme may have a
      detoxificant role related to the efflux transporter of the toxin.

PMID- 17017527
TI  - Nicotine induces brain CYP enzymes: relevance to Parkinson's disease.
AB  - Brain expression of cytochromes P450 2B6, 2D6 and 2E1 is higher in smokers, and
      is induced by nicotine in animals. These enzymes can metabolize many of the
      neurotoxins associated with Parkinson's disease. Since smoking is known to be
      protective against Parkinson's disease, we hypothesise that nicotine-induced
      elevation of brain CYPs in smokers may contribute to neuroprotection against
      Parkinson's disease. This supports the therapeutic use of nicotine to delay the
      progress of this disease.

PMID- 17017528
TI  - Genetic causes of Parkinson's disease: extending the pathway.
AB  - The functional characterization of identified disease genes in monogenic forms of
      Parkinson's disease (PD) allows first insights into molecular pathways leading to
      neurodegeneration and dysfunction of the nigrostriatal system. There is
      increasing evidence that disturbance of the ubiquitin proteasome pathway is one
      important feature of this process underscoring the relevance of protein
      misfolding and accumulation in the neurodegenerative process of PD. Other genes
      are involved in mitochondrial homeostasis and still others link newly identified
      signalling pathways to the established paradigm of oxidative stress in PD.
      Additional factors are posttranslational modifications of key proteins such as
      phosphorylation. Also, molecular data support the role of altered iron metabolism
      in PD. Here we describe known genes and novel genetic susceptibility factors and
      define their role in neurodegeneration.

PMID- 17017529
TI  - Progress in familial Parkinson's disease.
AB  - To date 11 forms of familial Parkinson's disease (PD) have been mapped to
      different chromosome loci, of which 6 genes have been identified as the causative
      genes, i.e., alpha-synuclein (SNCA), parkin, UCH-L1, PINK1, DJ-1, and LRRK2. For
      UCH-L1, additional families with this mutation are necessary before concluding
      that UCH-L1 is the definite causative gene for PARK5, as only one family so far
      has been reported. SNCA, UCH-L1, and LRRK2 mutations cause autosomal dominant PD
      and the remaining gene mutations autosomal recessive PD. Age of onset tends to be
      younger in familial PD compared with sporadic PD, particularly so in autosomal
      recessive PD. Generally familial cases respond to levodopa quite nicely and
      progression of the disease tends to be slower. It is an interesting question how
      familial PD-causing proteins are mutually related each other. In this article, we
      review recent progress in genetics and molecular biology of familial PD.

PMID- 17017530
TI  - Molecular mechanisms of nigral neurodegeneration in Park2 and regulation of
      parkin protein by other proteins.
AB  - Most of the patients with Parkinson's disease (PD) are sporadic. However, Since
      identification of monogenic forms of PD, the contribution of genetic factors to
      the pathogenesis of sporadic PD is proposed as one of major risk factors. Indeed,
      this is supported by the demonstration of the high concordance in twins,
      increased risk among relatives of PD patients in case control and family studies.
      Thus, the functional analysis for the gene products for familial PD provides us a
      good hint to elucidate the pathogenesis of nigral degeneration. For example,
      although alpha-synuclein is involved in a rare dominant form of familial PD with
      dopa responsive parkinsonian features, this molecule is a major component of and
      Lewy bodies (LBs). In contrast, Park2 (parkin-related disease) is the most
      frequent form among patients with young-onset PD. However, Park2 brains generally
      lack the formation of LBs. In the other word, parkin responsible for Park2 is
      essential for the formation of LBs. Thus, both alpha-synuclein and parkin are
      speculated to share a common pathway. Here, we reviewed the parkin function and
      molecular mechanisms of Park2.

PMID- 17017531
TI  - Parkin and defective ubiquitination in Parkinson's disease.
AB  - Parkinson's Disease (PD) is a common neurodegenerative disorder that is
      characterized by the progressive loss of dopamine (DA) neurons. Accompanying the
      loss the of DA neurons is the accumulation of Lewy bodies and neurites,
      intracytoplasmic proteinaceous inclusions that contain alpha-synuclein, synphilin
      1, components of the ubiquitin proteasomal pathway and parkin. Recent advances
      indicate that PD is due in some individuals to genetic mutations in alpha
      synuclein, DJ-1, PINK-1, LRRK2, and parkin. Understanding the molecular
      mechanisms by which mutations in familial-linked genes cause PD holds great
      promise for unraveling the mechanisms by which DA neurons degenerate in PD.
      Parkin is E3-ubiquitin-protein ligase that ubiquitinates itself and promotes its
      own degradation. Familial associated mutations of parkin have impaired ubiquitin
      ligase function suggesting that this may be the cause of familial autosomal
      recessive PD. Parkin might be required for formation of Lewy bodies as Lewy
      bodies are absent in patients with parkin mutations. Parkin interacts with and
      ubiquitinates the alpha-synuclein interacting protein, synphilin-1. Formation of
      Lewy-body-like ubiquitin-positive cytosolic inclusions occurs upon coexpression
      of alpha-synuclein, synphilin-1 and parkin. Nitric oxide inhibits Parkin's E-3
      ligase activity and its protective function by nitric oxide through S
      nitrosylation both in vitro and in vivo. Nitrosative and oxidative stress link
      parkin function with the more common sporadic form of Parkinson's disease and the
      related alpha-synucleinopathy, DLBD. Development of new therapies for PD and
      other disorders associated with nitrosative and oxidative stress may follow the
      elucidation of the pathways by which NO S-nitrosylates and inhibits parkin.
      Moreover, parkin and alpha-synuclein are linked in common pathogenic mechanism
      through their interaction with synphilin-1 and parkin may be important for the
      formation of Lewy bodies.

PMID- 17017532
TI  - PINK-1 and DJ-1--new genes for autosomal recessive Parkinson's disease.
AB  - Our genetic knowledge of Parkinson's disease (PD) is moving forward at an
      impressive speed. In less then 10 years family-based linkage analysis and
      positional cloning have led to the identification of several genes for familial
      forms of PD, which has been of critical importance to the scientific advance of
      PD research as the causal genes have offered new tools to model and understand
      pathways leading to neurodegeneration in PD.

PMID- 17017533
TI  - Clinical and pathologic features of families with LRRK2-associated Parkinson's
      disease.
AB  - The etiology for Parkinson's disease (PD) remains unknown. Genetic causes have
      been identified with several distinct mutations. Recently, 9 mutations involving
      a novel gene, leucine-rich repeat kinase 2 (LRRK2), have been identified as the
      cause of autosomal dominant PD in kindreds, with some of them previously linked
      to the PARK8 locus on chromosome 12. LRRK2 mutations are relatively common
      genetic causes of familial and sporadic PD. In addition, these mutations have
      been identified in diverse populations. The clinical and pathologic features of
      LRRK2-associated PD are indistinguishable from idiopathic PD; however,
      considerable clinical and pathologic variability exists even among kindreds. This
      short review highlights the clinical and pathologic features in LRRK2-associated
      parkinsonism.

PMID- 17017534
TI  - Molecular genetic findings in LRRK2 American, Canadian and German families.
AB  - A locus for a dominant form of PD has been mapped to the pericentromeric region
      of chromosome 12 in a Japanese family. We have confirmed linkage in two families
      of European ancestry and identified mutations in the gene for LRRK2 in these two
      and four additional families with dominantly inherited PD. All mutations are
      located in highly conserved domains of the gene. The LRRK2 protein belongs to the
      ROCO protein family, and includes a ras domaine (ras of complex proteins) and a
      protein kinase domain of the MAPKKK class and several other major functional
      domains. Within affected carriers of Families A and D, six post-mortem diagnoses
      reveal brainstem dopaminergic degeneration accompanied by strikingly diverse
      pathologies. These include abnormalities consistent with Lewy body Parkinson's
      disease, diffuse Lewy body disease, nigral degeneration without distinctive
      histopathology and progressive supranuclear palsy-like pathology. Hence, LRRK2
      may be central to the pathogenesis of several major neurodegenerative disorders
      associated with parkinsonism.

PMID- 17017535
TI  - Genetic and DAT imaging studies of familial parkinsonism in a Taiwanese cohort.
AB  - We here summarize the results of genetic investigations on a series of 82
      parkinsonian patients from 60 families in Taiwan. We found 13 parkin patients in
      7 families (12%), 2 PINK1 sibs from 1 family, and 1 LRRK2 patient from 1 family
      with I2012T mutation. We also identified SCA2 in 8 patients from 5 families (8%)
      and SCA3 in 3 patients from 1 family, all presenting with parkinsonian phenotype.
      In the available patients with parkin, PINK1, SCA2 and SCA3, the dopamine
      transporter (DAT) scan revealed that the reduction of uptake was primarily
      observed in the bilateral putamen, basically sharing a similar pattern with that
      in idiopathic Parkinson's disease. We concluded that the genetic causes
      contributed to about 25% of our series of familial parkinsonism. The parkin
      mutations and SCA2 were the most frequent genetic causes in our series with
      Chinese ethnicity. The results of DAT scan indicated that bilateral putamen was
      essentially involved in various genetically-caused familial parkinsonism.

PMID- 17017536
TI  - Neuroimaging in Parkinson's disease.
AB  - Structural imaging studies often reveal relatively limited findings in
      Parkinsonian disorders, as the most profound changes are neurochemical and hence
      better revealed by functional studies such as PET or SPECT. However, newer
      magnetic resonance techniques such as spectroscopy, diffusion weighted imaging,
      diffusion tensor imaging and magnetization transfer have shown promise in
      differentiating between idiopathic Parkinson's and the atypical parkinsonian
      disorders such as multiple system atrophy and progressive supranuclear palsy. We
      review here recent advances in functional imaging as well as in structural
      studies of basal ganglia disorders. Functional studies may give insights into
      mechanisms underlying disease pathogenesis, as well as neurochemical alterations.

PMID- 17017537
TI  - Transcranial sonography in the early and differential diagnosis of Parkinson's
      disease.
AB  - In recent years transcranial sonography (TCS) has become a widely used method for
      the visualization of the brain parenchyma through the intact scull. Using TCS,
      our group discovered changes of the echotexture--namely increased echogenicity-
      at the substantia nigra (SN) in about 90% of patients with Parkinson's disease
      (PD). These results assessed with an interrater reproducibility of r = 0.8 in
      several studies have been confirmed by several other groups. In contrast
      increased SN echogenicity is rarely found in patients with atypical or
      symptomatic Parkinsonian syndromes, providing a valuable tool for differential
      diagnosis. Interestingly, increased SN echogenicity can also be found in about 8
      to 10% of healthy subjects. In PET analyses more than 60% of these clinically
      healthy individuals show a subclinical reduction of the striatal 18F-Dopa uptake
      indicating an alteration of the dopaminergic nigrostriatal system and nigral cell
      loss. Furthermore, it was possible to demonstrate that this ultrasound finding
      has a functional impact as subjects with an increased echogenicity of the SN (i)
      showed more frequently clinical symptoms of asymmetric hypokinesia with
      increasing age and (ii) developed more often and more severe Parkinsonian side
      effects when treated with neuroleptic therapy for neuropsychiatric disorders.
      Longitudinal studies indicate that the ultrasound signal does not change in the
      course of the disease. Moreover, presymptomatic carriers of mutations causative
      for monogenetic PD display the same echofeature as their relatives already
      affected by the disease. These findings indicate that increased SN echogenicity
      constitutes a biomarker for vulnerability of the nigrostriatal system in healthy
      subjects and eventually PD in a subgroup of persons with additional risk factors.

PMID- 17017538
TI  - How to judge animal models of Parkinson's disease in terms of neuroprotection.
AB  - Ideally, animal models of Parkinson's should reproduce the clinical manifestation
      of the disease, a loss of some but not all dopaminergic neurons, a loss of some
      non dopaminergic neurons and alpha-synuclein positive inclusions resembling Lewy
      bodies. There are at least three ways to develop animal models of PD. The first
      two are based on the etiology of the disease and consist in 1) reproducing in
      animals the mutations seen in inherited forms of PD; 2) intoxicating animals with
      putative environmental toxins causing PD. The last method currently used, which
      is not exclusive of the first two, is to try to reproduce the molecular or
      biochemical changes seen post-mortem in the brain of patients with PD. In this
      review we discuss the advantages and the drawbacks in term of neuroprotection of
      the currently used models.

PMID- 17017539
TI  - Limitations of cellular models in Parkinson's disease research.
AB  - Cell cultures for Parkinson's disease research have the advantage of virtually
      unlimited access, they allow rapid screening for disease pathogenesis and drug
      candidates, and they restrict the necessary number of animal experiments.
      Limitations of cell cultures, include that the survival of neurons is dependent
      upon the culture conditions; that the cells do not develop their natural neuronal
      networks. In most cases, neurons are deprived from the physiological afferent and
      efferent connections. In Parkinson's disease research, mesencephalic slice
      cultures, primary immature dopaminergic neurons and immortalized cell lines-
      either in a proliferating state or in a differentiated state--are used. Neuronal
      cultures may be plated in the presence or absence of glial cells and serum. These
      different culture conditions as well as the selection of outcome parameters
      (morphological evaluation, viability assays, biochemical assays, metabolic
      assays) have a strong influence on the results of the experiments and the
      conclusions drawn from them. A primary example is the question of whether L-Dopa
      is toxic to dopaminergic neurons or whether it provides neurotrophic effects: In
      pure, neuronal-like cultures, L-Dopa provides toxicity, whereas in the presence
      of glial cells, it provides trophic effects when applied. The multitude of
      factors that influence the data generated from cell culture experiments indicates
      that in order to obtain clear-cut and unambiguous results, investigators need to
      choose their model carefully and are encouraged to verify their main results with
      different models.

PMID- 17017540
TI  - The rotenone model of parkinsonism--the five years inspection.
AB  - Treatment of rats with rotenone has been proposed in the year 2000 to provide an
      animal model of idiopathic Parkinson's disease. We review here the experience
      that has been gained meanwhile with this model. The published data suggest that
      the model does not ideally reproduce the pathophysiology of Parkinson's disease,
      that Rotenone treatment does not cause a purely neurodegenerative concondition,
      that the Rotenone model does not ideally recapitulate the motor symptoms of
      Parkinson's disease, that degeneration of the dopaminergic neurons is highly
      variable, that striatal neurons appear to degenerate more consistently than
      neurons in the substantia nigra, and that cytoplasmic accumulation of the tau
      protein is more abundant than alpha-synuclein aggregation in severely lesioned
      animals. In summary, these data suggest that Rotenone-treated rats model atypical
      Parkinsonism rather than idiopathic Parkinson's disease.

PMID- 17017541
TI  - Controversies on new animal models of Parkinson's disease pro and con: the
      rotenone model of Parkinson's disease (PD).
AB  - A general complex I deficit has been hypothesized to contribute to
      neurodegeneration in Parkinson's disease (PD) and all toxins used to destroy
      dopaminergic neurons are complex I inhibitors. With MPTP or 6-OHdopamine, this
      hypothesis can not be tested since these toxins selectively accumulate in the
      dopaminergic neurons. However with rotenone, which penetrates all cells, the
      hypothesis can be tested. Thus, the proof of the hypothesis is whether or not
      rotenone-induced neurodegeneration mimics the degenerative processes underlying
      PD. Low doses of rotenone (1.5 or 2.5 mg/kg in oil i.p.) were administered to
      Sprague Dawley rats on a daily basis. After about 20 days of treatment, signs of
      parkinsonism occurred and the concentrations of NO and peroxidase products rose
      in the brain, especially in the striatum. After 60 days of treatment, rotenone
      had destroyed dopaminergic neurons. Behaviourally, catalepsy was evident, a
      hunchback posture and reduced locomotion. Other transmitter systems were not, or
      much less affected. L-DOPA-methylester (10 mg/kg plus decarboxylase inhibition)
      potently reversed the parkinsonism in rats. Also when infused directly into the
      dopaminergic neurons, rotenone produced parkinsonism which was antagonized by L
      DOPA. Some peripheral symptoms of PD are mimiced by rotenone too, for example a
      low testosterone concentration in the serum and a loss of dopaminergic amacrine
      cells in the retina. These results support the hypothesis of an involvement of
      complex I in PD and render the rotenone model as a suitable experimental model.
      The slow onset of degeneration make it suitable also to study neuroprotective
      strategies. Evidence that rotenone-induced neurodegeneration spreads beyond the
      dopaminergic system is not contradictory given that, according to the new staging
      studies, also degeneration in PD is not confined to dopamine neurons.

PMID- 17017542
TI  - Proposed animal model of severe Parkinson's disease: neonatal 6-hydroxydopamine
      lesion of dopaminergic innervation of striatum.
AB  - Rats lesioned shortly after birth with 6-hydroxydopamine are posed as a near
      ideal model of severe Parkinson's disease, because of the non-lethality of the
      procedure, near-total destruction of nigrostriatal dopaminergic fibers, near
      total dopamine (DA)-denervation of striatum, reproducibility of effect, and
      relative absence of overt behavioral effects--there is no aphasia, no adipsia,
      and no change in motor activity. In vivo microdialysis findings reinforce the
      utility of the animal model, clearly demonstrating L-DOPA beneficial actions
      without an increase in hydroxyl radical production.

PMID- 17017543
TI  - Alpha-synuclein overexpression model.
AB  - OBJECTIVES: To elucidate the role of alpha-synuclein in the pathogenesis of
      Parkinson's disease (PD), both human alpha-synuclein transgenic mice and targeted
      overexpression of human alpha-synuclein in rat substantia nigra (SN) by viral
      vector-based methods have been studied, however little is known about the
      pathogenetic changes of dopaminergic neuron loss. Therefore, it is necessary to
      address whether the pathogenetic changes in the brains of patients with PD are
      recapitulated in these models. METHODS AND RESULTS: We used the recombinant adeno
      associated viral (rAAV) vector system for human alpha-synuclein gene transfer to
      rat SN and observed approximately 50% loss of dopaminergic neurons in SN at 13
      weeks after infection. In the slower progression of neurodegeneration, we
      identified several important features in common with the pathogenesis of PD, such
      as phosphorylation of alpha-synuclein at Ser129 and activation of caspase-9. Both
      findings were also evident in cortical tissues overexpressing alpha-synuclein via
      rAAV. CONCLUSIONS: Our results indicate that overexpression of alpha-synuclein
      via rAAV apparently recapitulates several important features of brains with PD
      and dementia with Lewy bodies (DLB), and thus alpha-synucleinopathy described
      here is likely to be an ideal model for the study of the pathogenesis of PD and
      DLB. This model is also useful for the gene therapy research.

PMID- 17017544
TI  - Kynurenines, Parkinson's disease and other neurodegenerative disorders:
      preclinical and clinical studies.
AB  - The kynurenine pathway is the main pathway of tryptophan metabolism. L-kynurenine
      is a central compound of this pathway since it can change to the neuroprotective
      agent kynurenic acid or to the neurotoxic agent quinolinic acid. The break-up of
      these endogenous compounds' balance can be observable in many disorders. It can
      be occur in neurodegenerative disorders, such as Parkinson's disease,
      Huntington's and Alzheimer's disease, in stroke, in epilepsy, in multiple
      sclerosis, in amyotrophic lateral sclerosis, and in mental failures, such as
      schizophrenia and depression. The increase of QUIN concentration or decrease of
      KYNA concentration could enhance the symptoms of several diseases. According to
      numerous studies, lowered KYNA level was found in patients with Parkinson's
      disease. It can be also noticeable that KYNA-treatment prevents against the QUIN
      induced lesion of rat striatum in animal experiments. Administrating of KYNA can
      be appear a promising therapeutic approach, but its use is limited because of its
      poorly transport across the blood-brain barrier. The solution may be the
      development of KYNA analogues (e.g. glucoseamine-kynurenic acid) which can pass
      across this barrier and disengaging in the brain, then KYNA can exert its
      neuroprotective effects binding at the excitatory glutamate receptors, in
      particular the NMDA receptors. Furthermore, it seems hopeful to use kynurenine
      derivatives (e.g. 4-chloro-kynurenine) or enzyme inhibitors (e.g. Ro-61-8048) to
      ensure an increased kynurenic acid concentration in the central nervous system.

PMID- 17017545
TI  - What's new? Clinical progression and staging of Parkinson's disease.
AB  - Several new advances facilitate current understanding of the progression of
      Parkinson's disease. The application of statistical modeling techniques has
      helped to estimate rates of clinical decline in the context of symptomatic
      interventions. These approaches may allow a new means for testing neuroprotection
      effects even when patients are on dopaminergic treatment. Further, the
      development of new rating scales, specifically the Movement Disorder Society
      initiated revision of the Unified Parkinson's Disease Rating Scale has
      capitalized on a greater clinical appreciation of non-motor elements of
      Parkinson's disease. Finally, adaptations of new technologies that are computer
      based and enable data transmission from at-home environments allow researchers to
      capture disease impairment and disability with potentially greater precision and
      much more frequently than permissible in a hospital clinic or practice setting.

PMID- 17017546
TI  - Parkinson's disease: premotor clinico-pathological correlations.
AB  - Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/
      akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's
      disease (PD). Progressive loss of nigral neurons with Lewy bodies is considered
      an essential neuropathological feature. Recent studies, however, indicate that
      nigral degeneration is only a part of this synucleinopathy, and clinical symptoms
      go far beyond motor parkinsonism. Olfactory disturbances, autonomic dysfunction,
      pain, sleep fragmentation, depression, and dementia with or without psychosis are
      frequently seen. The variability in the expression of these signs and symptoms
      suggests multiple causes and/or pathogeneses within the present diagnostic
      disease entity. In this article, a recently proposed staging of PD-related brain
      pathology will be correlated with the various clinical expressions. It will be
      argued that the specific topographical sequence of the pathology, depending on
      the extent and progression of the degenerative process at defined sites, may
      explain the individually variable expression of this disease.

PMID- 17017547
TI  - Detection of preclinical Parkinson's disease along the olfactory trac(t).
AB  - The association of Parkinson's disease (PD) with an impaired sense of smell was
      first reported about thirty years ago. Since then, it has become quite firmly
      established that olfactory dysfunction is one of the first and most prevalent
      clinical manifestations of this disorder. Recent data from an ongoing prospective
      study indicate that otherwise unexplained hyposmia in first degree relatives of
      patients with sporadic PD is associated with an increased risk of developing
      clinical PD of at least 13%. In particular, a combination of impaired olfactory
      function and reduced striatal [123I]beta-CIT binding on a baseline SPECT scan
      appears to be a strong predictor of a subsequent diagnosis of PD. Pathological
      studies support these observations by demonstrating that the anterior olfactory
      structures may be one of the induction sites of PD pathology. Considering that
      there is a doubling rather than a loss of dopaminergic neurons in the olfactory
      bulb in PD patients, the pathophysiology of olfactory dysfunction in PD is far
      from being elucidated. Studying prodromal manifestations of PD, such as olfactory
      dysfunction, and their underlying pathophysiology may greatly contribute to the
      development of treatment strategies that focus on preclinical detection and
      slowing down disease progression.

PMID- 17017548
TI  - The clinical approach to gait disturbances in Parkinson's disease; maintaining
      independent mobility.
AB  - Gait is affected in all stages of Parkinson's disease (PD) and is one of the
      hallmarks for disease progression. The fear of getting into the wheel chair is
      one of the first thoughts many patients ask about when the diagnosis of PD is
      given. At the early stages of the disease gait disturbances are present and can
      be measured but in most patients it does not cause significant functional
      disturbances. In contrast, as the disease progress, gait disturbances and
      postural control abnormalities are becoming major causes for lost of mobility and
      falls. These unfortunate consequences should be forecasted at the early stages of
      the disease and a preventive approach should be taken. Treatment of gait
      disturbances at the early stages of the disease is mainly to encourage patients
      to exercise and walk daily and by drugs in those with disabling symptoms. At the
      advanced stages, treatment should be aggressive in order to keep the patient
      walking safely. Drugs, physiotherapy and functional neurosurgery should be used
      wisely for best outcomes and least side effects. When time comes and the risk of
      falls is very significant, walking aids should be suggested and if no other
      option is left, wheel chair is a very reasonable option to maintain mobility out
      of home, preserving quality of life and avoiding falls with all it severe
      consequences.

PMID- 17017549
TI  - Getting around and communicating with the environment: visual cognition and
      language in Parkinson's disease.
AB  - Vision in PD. In PD an impairment of dopaminergic neurons of the preganglionic
      retina and a defect of the retinal nerve fibers (axons of the retinal ganglion
      cells) has been demonstrated and a correlation of loss of spatial contrast
      sensitivity, with the progression of motor impairment in PD has been described.
      These low level visual deficits contribute but do not directly explain
      behavioural visual deficits in PD involving spatial cognition, internal
      representation, space navigation and visual categorization. Language deficits in
      non-demented PD patients can include impairments in comprehension, verbal
      fluency, and naming. Comprehension deficits become evident when patients are
      required to process sentences with non-canonical, irregular grammatical
      structures. Semantic memory deficits may result in the impairments in category
      fluency and confrontational naming. Selective language deficits may be due to
      impaired dynamics of the "phonological loop" connecting the pre-frontal cortex
      and the basal ganglia. A more encompassing linguistic and functional model of PD
      specific language impairments would be useful for evaluating language deficits in
      the context of motor dysfunction.

PMID- 17017550
TI  - Cardiovascular aspects of Parkinson disease.
AB  - This chapter provides an update about cardiovascular aspects of Parkinson disease
      (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early
      finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of
      levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD
      + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH.

PMID- 17017551
TI  - Multiple system atrophy and autonomic failure.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that
      affects adults. It is characterised by autonomic failure affecting many systems;
      cardiovascular, urinary, sexual, gastrointestinal and sudomotor, amongst others.
      In addition there are motor deficits, resulting in both parkinsonian and/or
      cerebellar features. This review will outline the clinical features,
      investigations and management of MSA, with a particular emphasis on autonomic
      failure.

PMID- 17017552
TI  - Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an
      overview.
AB  - Sleep disturbances are frequent in Parkinson disease. These disorders can be
      broadly categorized into those that involve nocturnal sleep and excessive daytime
      sleepiness. The disorders that are often observed during the night in PD include
      sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea,
      Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder.
      Excessive daytime sleepiness is also a common occurrence in PD. EDS can arise
      from several etiologies, and patients may have more than one etiology
      responsible. The causes of EDS include nocturnal sleep disorder with sleep
      deprivation and resulting daytime somnolence, the effect of drugs used to treat
      PD, and possibly neurodegeneration of central sleep/wake areas. Appropriate
      diagnosis of the sleep disturbance affecting a PD patient can lead to specific
      treatments that can consolidate nocturnal sleep and enhance daytime alertness.

PMID- 17017553
TI  - Sleep and wakefulness disturbances in Parkinson's disease.
AB  - Patients with Parkinson's disease experience prominent difficulties in
      maintaining sleep, painful night-time abnormal movements, and daytime sleepiness,
      sometimes culminating in sleep attacks. Recent insights into the pathophysiology
      of sleep disorders in PD points to a complex interaction between movement
      disorders, side-effects of dopamine agents and lesions in sleep-wake regulating
      systems. Treatment with dopamine agonists provides a twice higher risk of daytime
      sudden sleep episodes than levodopa, with no difference between ergotic and non
      ergotic compounds. Insomnia can be improved by a better control of night-time
      disability, restless legs syndrome and dystonia using subthalamic nucleus
      stimulation or night-time levodopa. A specific REM sleep disorder contributes to
      REM sleep behavior disorder and also to hallucinations (suggesting they could be
      awake dreams) and excessive daytime sleepiness. The management of sleep and
      alertness problems requires to analyze their potential causes, to monitor night
      time and daytime sleep, and to subtly adjust psychotropic and dopaminergic
      treatment.

PMID- 17017554
TI  - Parkinson's disease dementia: what's in a Lewy body?
AB  - This brief review deals with pathological aspects of dementia associated with
      Parkinson's disease (PDD). PDD has been variably linked with cortical Lewy body
      topography and density. alpha-Synuclein and Alzheimer-type pathology frequently
      co-exist, suggesting that a combination of pathology related to protein
      dysmetabolism, possibly with synergistic protein-protein interaction, underpins
      the cognitive impairment in PDD. Dementia may therefore ensue when a "toxic
      threshold" is reached, irrespective of the combination of pathologies involved in
      reaching that threshold. The nature of this putative protein-protein interaction
      needs to be further elucidated, and also whether there are specific clinical
      correlates of the pathological substrate. Serum and cerebrospinal fluid proteins
      or imaging techniques may be useful in future as biomarkers to identify the
      relative contribution of Lewy-related and Alzheimer-type pathology in a given
      case of PDD and to inform the rational use of drugs that can reduce alpha
      synuclein aggregation and beta-amyloid production.

PMID- 17017555
TI  - Role of microglia in inflammation-mediated degeneration of dopaminergic neurons:
      neuroprotective effect of interleukin 10.
AB  - Inflammation in the brain has been recognized to play an increasingly important
      role in the pathogenesis of several neurodegenerative disorders, including
      Parkinson's disease and Alzheimer's disease. Inflammation-mediated
      neurodegeneration involves activation of the brain's resident immune cells, the
      microglia, which produce proinflammatory and neurotoxic factors including
      cytokines, reactive oxygen species (ROS), nitric oxide, and eicosanoids that
      directly or indirectly cause neurodegeneration. In this study, we report that IL
      10, an immunosuppressive cytokine, reduced the inflammation-mediated degeneration
      of dopaminergic (DA) neurons through the inhibition of microglial activation.
      Pretreatment of rat mesencephalic neuronglia cultures with IL-10 significantly
      attenuated the lipopolysaccharide (LPS) induced DA neuronal degeneration. The
      neuroprotective effect of IL-10 was attributed to inhibition of LPS-stimulated
      microglial activation. IL-10 significantly inhibited the microglial production of
      tumor necrosis factor alpha (TNF-alpha), nitric oxide, ROS and superoxide free
      radicals after LPS stimulation.

PMID- 17017556
TI  - Role of cytokines in inflammatory process in Parkinson's disease.
AB  - We investigated whether the cytokines produced in activated microglia in the
      substantia nigra (SN) and putamen in sporadic Parkinson's disease (PD) are
      neuroprotective or neurotoxic. In autopsy brains of PD, the number of MHC class
      II (CR3/43)-positive activated microglia, which were also ICAM-1 (CD 54)-, LFA-1
      (CD 11a)-, TNF-alpha-, and IL-6-positive, increased in the SN and putamen during
      progress of PD. At the early stage activated microglia were mainly associated
      with tyrosine hydroxylase (TH)-positive neurites in the putamen, and at the
      advanced stage with damaged TH-positive neurons in the SN. The activated
      microglia in PD were observed not only in the nigro-striatal region, but also in
      various brain regions such as the hippocampus and cerebral cortex. We examined
      the distribution of activated microglia and the expression of cytokines and
      neurotrophins in the hippocampus of PD and Lewy body disease (LBD). The levels of
      IL-6 and TNF-alpha mRNAs increased both in PD and LBD, but those of BDNF mRNA and
      protein drastically decreased specifically in LBD, in which neuronal loss was
      observed not only in the nigro-striatum but also in the hippocampus. The results
      suggest activated microglia in the hippocampus to be probably neuroprotective in
      PD, but those to be neurotoxic in LBD. As an evidence supporting this hypothesis,
      two subsets of microglia were isolated from mouse brain by cell sorting: one
      subset with high production of reactive oxygen species (ROS) and the other with
      no production of ROS. When co-cultured with neuronal cells, one microglia clone
      with high ROS production was neurotoxic, but another clone with no ROS production
      neuroprotective. On the other hand, Sawada with coworkers found that a
      neuroprotective microglial clone in a culture experiment converted to a toxic
      microglial clone by transduction of the HIV-1 Nef protein with increasing NADPH
      oxidase activity. Taken together, all these results suggest that activated
      microglia may change in vivo from neuroprotective to neurotoxic subtsets as
      degeneration of dopamine neurons in the SN progresses in PD. We conclude that the
      cytokines from activated microglia in the SN and putamen may be initially
      neuroprotective, but may later become neurotoxic during the progress of PD. Toxic
      change of activated microglia may also occur in Alzheimer's disease and other
      neurodegenerative diseases in which inflammatory process is found.

PMID- 17017557
TI  - Surgical therapy for Parkinson's disease.
AB  - High frequency stimulation (HFS) has become the main alternative to medical
      treatment, due to its reversibility, adaptability, and low morbidity. Initiated
      in the thalamus (Vim) for the control of tremor, HFS has been applied to the
      Pallidum (GPi), and then to the subthalamic nucleus (STN), suggested by
      experiments in MPTP monkeys. STN-HFS is highly efficient on tremor, rigidity and
      bradykinesia and is now widely applied. Criteria for success are correct patient
      selection and precise electrode placement. The best outcome predictor is the
      response to Levodopa. The mechanisms of action might associate inhibition of cell
      firing, jamming of neuronal message and exhaustion of synaptic neurotransmitter
      release. The inhibition of glutamate STN release could be neuroprotective on
      nigral cells. Animal experiments support this hypothesis, not contradicted by the
      long-term follow up of patients. Neuroprotection might have considerable impact
      on the management of PD patient and warrants clinical trials.

PMID- 17017558
TI  - Deep brain stimulation for the treatment of Parkinson's disease.
AB  - Approximately 30,000 patients have been treated throughout the world with deep
      brain stimulation for Parkinson's disease and other conditions. With accumulating
      experience, there has been an appreciation of the important benefits of this
      procedure, including the alleviation of disability and improvement in the quality
      of life. We have also become aware of some limitations of DBS surgery. Among the
      important issues that remain to be resolved are the timing of surgery, whether
      early or late in the course of the disease, and the best target for the
      individual patient, including a reassessment of the relative merits of globus
      pallidus versus subthalamic nucleus surgery. A better understanding of the
      symptoms that are resistant to both levodopa therapy and DBS surgery is also
      required.

PMID- 17017559
TI  - Deep brain stimulation in Parkinson's disease patients: biochemical evidence.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's
      disease (PD) patients augments STN-driven excitation of the internal globus
      pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we
      report the biochemical effects of STN-DBS in two basal ganglia stations (putamen-
      PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA).
      In six advanced PD patients undergoing surgery, microdialysis samples were
      collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP
      was measured in the GPi and PUT as an index of glutamatergic transmission,
      whereas GABA was measured in the VA. During clinically effective STN-DBS, we
      found a significant decrease in GABA extracellular concentrations in the VA (
      25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT
      (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area:
      it activates the STN-GPi pathway while inhibiting the GPi-VA one. These findings
      support a thalamic dis-inhibition, as the main responsible for the clinical
      effect of STN-DBS. This, in turn, re-establishes a more physiological level of
      PUT activity.

PMID- 17017560
TI  - Neurosurgery in Parkinson's disease: the doctor is happy, the patient less so?
AB  - Despite the overall excellent outcome of neurosurgery in patients with
      Parkinson's disease, there is often a contrast between the improvement in motor
      disability and the difficulties of patients to reintegrate a normal life. In this
      study, the personal, familial and professional difficulties experienced by
      patients two years after bilateral high frequency stimulation of the subthalamic
      nucleus were carefully analyzed. To avoid such socio-familial maladjustment, we
      strongly suggest taking into consideration the patients' psychological and social
      context before the operation and during the post-operative follow-up.

PMID- 17017561
TI  - Placebo effect and dopamine release.
AB  - The placebo effect can be encountered in a great variety of medical conditions,
      but is particularly prominent in pain, depression and Parkinson's disease. It has
      been shown that placebo responses play a part in the effect of any type of
      treatment for Parkinson's disease, including drug therapy, deep brain stimulation
      and dopamine tissue transplantation. Recent studies have demonstrated that the
      placebo effect in Parkinson's disease is related to the release of substantial
      amounts of endogenous dopamine in both the dorsal and ventral striatum. As the
      ventral striatum is involved in reward processing, these observations suggest
      that the placebo effect may be linked to reward mechanisms. In keeping with this
      placebo-reward model, most recent experiments have shown activation of the reward
      circuitry in association with placebo responses in other disorders. In addition,
      as dopamine is the major neurotransmitter in the reward circuitry, the model
      predicts that the release of dopamine in the ventral striatum could be involved
      in mediating placebo responses not only in Parkinson's but also in other medical
      conditions.

PMID- 17017562
TI  - A new look at levodopa based on the ELLDOPA study.
AB  - Levodopa has been the gold standard for Parkinson's disease (PD) therapy since it
      was successfully introduced in 1967. But in the years since then, after
      recognizing that levodopa often leads to the motor complications of wearing-off
      and dyskinesias, there have been debates among clinicians as to when levodopa
      therapy should be started. Delaying therapy was advocated for the purpose of
      delaying the development of these motor complications. This became more popular
      as the dopamine agonists became available. Although less potent than levodopa in
      ameliorating the symptoms of PD, they were much less likely to produce the
      unwanted motor complications, even though they had their own adverse effects.
      When it was recognized that dopamine, itself, might be a factor leading to the
      death of dopaminergic neurons through its contributing to the formation of
      oxyradicals, a new concern arose, namely that levodopa, through its conversion to
      brain dopamine, might add to the existing oxidative stress and possibly enhance
      neurodegeneration of dopaminergic neurons. Though widely debated and without
      definite evidence, this possibility was sufficient to make some clinicians have
      further reason to delay the start of levodopa therapy. The ELLDOPA study was
      created to test this hypothesis. The clinical component of the study failed to
      find an enhancement of PD symptoms after levodopa was withdrawn following 40
      weeks of levodopa therapy. Rather, the clinical results indicated that the
      symptoms had progressed much less than placebo, and in a dose-response manner.
      This suggests that levodopa may actually have neuroprotective properties. The
      uncertainty that a 2-week withdrawal of levodopa may not have entirely eliminated
      its symptomatic benefit and the discordant results of the neuroimaging component
      of the ELLDOPA study have created even more uncertainty that levodopa is
      neuroprotective. A survey of neurologists who treat PD patients showed that the
      vast majority of these clinicians do not believe levodopa is neuroprotective, and
      they remain concerned about the drug's likelihood of inducing motor
      complications. Thus, the ELLDOPA study failed to change the treating pattern of
      PD, and the clinicians require more convincing evidence of either neuroprotection
      or neurotoxicity of levodopa before they would alter their treatment approach.

PMID- 17017563
TI  - Thirty five years of experience in the treatment of Parkinson's disease with
      levodopa and associations.

PMID- 17017564
TI  - Concerning neuroprotective therapy for Parkinson's disease.
AB  - Studying potential neuroprotective therapy for Parkinson's disease is
      conceptually problematic because of the heterogenous nature of the Parkinson's
      syndrome and complexities in operational definitions for neuroprotection. The
      current literature concerning neuroprotection provides no convincing evidence of
      any treatment as definitively neuroprotective in Parkinson's disease. Recent
      clinical trials and novel trial designs are reviewed that may identify meaningful
      therapy, resulting in maintenance of neurological function and quality of life
      for persons with Parkinson's disease.

PMID- 17017565
TI  - Triggering endogenous neuroprotective mechanisms in Parkinson's disease: studies
      with a cellular model.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has been implicated in the
      protection of dopamine (DA) neurons from oxidative stress in animal models of
      Parkinson's disease (PD). We have now shown that GDNF can also protect against
      the effects of 6-hydroxydopamine (6-OHDA) in a dopaminergic cell line and in
      cultures of primary DA neurons prepared from rat substantia nigra (SN). This
      appears to involve a rapid and transient increase in the phosphorylation of
      several isoforms of extracellular signal-regulated kinase (ERK). Our evidence
      indicates that ERK activation also can be modulated by reactive oxygen species
      (ROS), including those generated by endogenous DA. Identification of the ways by
      which these pathways can be triggered should provide insights into the
      pathophysiology of PD, and may offer useful avenues for retarding the progression
      of the disorder.

PMID- 17017566
TI  - Ladostigil, a novel multifunctional drug for the treatment of dementia co-morbid
      with depression.
AB  - Ladostigil is a novel drug that inhibits acetyl and butyrylcholinesterase, and
      monoamine oxidase (MAO) A and B selectively in the brain. It reverses memory
      deficits induced by chronic inhibition of cortical cytochrome oxidase in rats and
      has anxiolytic and antidepressant-like activity in prenatally-stressed rats.
      Ladostigil also prevents oxidative-nitrative stress induced in astrocytes in the
      hippocampal CA1 region following icv injection of STZ in rats which also impairs
      their episodic memory. The unique combination of ChE and MAO enzyme inhibition
      combined with neuroprotection makes ladostigil a potentially useful drug for the
      treatment of dementia in subjects that also have extrapyramidal dysfunction and
      depression.

PMID- 17017567
TI  - M30, a novel multifunctional neuroprotective drug with potent iron chelating and
      brain selective monoamine oxidase-ab inhibitory activity for Parkinson's disease.
AB  - Iron and monoamine oxidase activity are increased in brain of Parkinson's disease
      (PD). They are associated with autoxidation and oxidative deamination of dopamine
      by MAO resulting in the generation of reactive oxygen species and the onset of
      oxidative stress to induce neurodegeneration. Iron chelators (desferal, Vk-28 and
      clioquinol) but not copper chelators have been shown to be neuroprotective in the
      6-hydroxydoapmine and MPTP models of Parkinson's disease (PD), as are monoamine
      oxidase B inhibitors such as selegiline and rasagiline. These findings prompted
      the development of multifunctional anti PD drugs possessing iron chelating
      phamacophore of VK-28 and the propargylamine MAO inhibitory activity of
      rasagiline. M30 is a potent iron chelator, radical scavenger and brain selective
      irreversible MAO-A and B inhibitor, with little inhibition of peripheral MAO. It
      has neuroprotective activity in in vitro and in vivo models of PD and unlike
      selective MAO-B inhibitors it increases brain dopamine, serotonin and
      noradrenaline. These findings indicate beside its anti PD action, it may also
      possess antidepressant activity, similar to selective MAO-A and nonselective MAO
      inhibitors. These properties make it an ideal anti PD drug for which it is being
      developed.

PMID- 17017569
TI  - Anti-apoptotic gene therapy in Parkinson's disease.
AB  - Apoptosis, whether caspase-dependent or caspase-independent, has been implicated
      as one of the important mechanisms leading to the death of dopaminergic neurons
      in the substantia nigra of Parkinson's disease patients. Major advances of our
      understanding of apoptosis have been achieved in studies of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice and monkeys and 6
      hydroxydopamine (6-OHDA) toxicity in rats and monkeys. The use of viral vectors
      to either express anti-apoptotic proteins or to downregulate pro-apoptotic
      proteins has the major advantage of addressing selective molecular targets,
      bypassing the blood-brain-barrier to specifically target the nigrostriatal
      pathway by their stereotaxic application and by the choice of the appropriate
      virus and promotor. Used thus far have been virus-mediated overexpression of
      inhibitor of apoptosis proteins, inhibitors of the c-jun-N-terminal kinase (JNK)
      pathway, inhibitors of calpains and dominant negative inhibitors of the protease
      activating factor (APAF)-1 and cdk5. Most studies implicate the endogenous,
      mitochondrial pathway in the apoptosis of dopaminergic neurons. The results
      suggest that only an inhibition of this pathway upstream of caspase activation
      will also result in the protection of nigrostriatal dopaminergic terminals and
      behavioral benefit, whereas an inhibition of caspases alone may not be sufficient
      to prevent the degeneration of terminals, although it may promote the survival of
      neuronal cell bodies for some time.

PMID- 17017568
TI  - Involvement of multiple survival signal transduction pathways in the
      neuroprotective, neurorescue and APP processing activity of rasagiline and its
      propargyl moiety.
AB  - Our recent studies aimed to elucidate the molecular and biochemical mechanism of
      actions of the novel anti-Parkinson's drug, rasagiline, an irreversible and
      selective monoamine oxidase (MAO)-B inhibitor and its propargyl moiety,
      propargylamine. In cell death models induced by serum withdrawal in rat PC12
      cells and human SH-SY5Y neuroblastoma cells, both rasagiline and propargylamine
      exerted neuroprotective and neurorescue activities via multiple survival
      pathways, including: stimulation of protein kinase C (PKC) phosphorylation; up
      regulation of protein and gene levels of PKCalpha, PKCepsilon and the anti
      apoptotic Bcl-2, Bcl-xL, and Bcl-w; and up-regulation of the neurotrophic
      factors, BDNF and GDNF mRNAs. Rasagiline and propargylamine inhibited the
      cleavage and subsequent activation of pro-caspase-3 and poly ADP-ribose
      polymerase. Additionally, these compounds significantly down-regulated PKCgamma
      mRNA and decreased the level of the pro-apoptotic proteins, Bax, Bad, Bim and
      H2A.X. Rasagiline and propargylamine both regulated amyloid precursor protein
      (APP) processing towards the non-amyloidogenic pathway. These structure-activity
      studies have provided evidence that propargylamine promoted neuronal survival via
      neuroprotective/neurorescue pathways similar to that of rasagiline. In addition,
      recent study demonstrated that chronic low doses of rasagiline administered to
      mice subsequently to 1 methyl-4 phenyl 1,2,3,6 tetrahydropyridine (MPTP), rescued
      dopaminergic neurons in the substantia nigra pars compacta via activation of the
      Ras-PI3K-Akt survival pathway, suggesting that rasagiline may possess a disease
      modifying activity.

PMID- 17017570
TI  - The discovery of the pressor effect of DOPS and its blunting by decarboxylase
      inhibitors.
AB  - In the 1950s it was found that an artificial aminoacid, 3,4-threo
      dihydroxyphenylserine (DOPS), was converted to norepinephrine (NE) in a single
      step by the enzyme L-aromatic amino acid decarboxylase (AADC), bypassing the need
      for the rate limiting enzyme dopamine beta hydroxylase. Trying to replicate the
      success of dihydroxyphenylalanine (DOPA) in the treatment of Parkinson disease,
      treatment with DOPS was attempted in patients with autonomic failure who have
      impaired NE release. DOPS improved orthostatic hypotension in patients with
      familial amyloid polyneuropathy, congenital deficiency of dopamine beta
      hydroxylase, pure autonomic failure and multiple system atrophy. DOPS pressor
      effect is due to its conversion to NE outside the central nervous system because
      concomitant administration of carbidopa, an inhibitor of AADC that does not cross
      the blood-brain barrier, blunted both the increase in plasma NE and the pressor
      response. DOPS pressor response is not dependent on intact sympathetic terminals
      because its conversion to NE also occurs in non-neuronal tissues.

PMID- 17017571
TI  - Pathophysiology of dystonia.
AB  - Understanding of the pathophysiology of dystonia derives primarily from studies
      of focal dystonias. Physiological investigations have revealed a number of
      abnormalities that may reflect the genetic substrate that predisposes certain
      individuals to develop dystonia. There is a loss of inhibition in the central
      nervous system, and a loss of surround inhibition specifically. Plasticity is
      increased, and there are sensory abnormalities. Which of these disorders is
      primary is uncertain.

PMID- 17017572
TI  - Genetics of dystonia.
AB  - Primary torsion dystonia (PTD) has a broad clinical spectrum, with earlier onset
      of symptoms associated with more generalized muscle involvement. The causes for
      most dystonia are unknown although several monogenic subtypes have been
      identified. One important genetic cause of PTD is DYT1; a three base pair
      deletion in this gene is a major cause for early-onset dystonia. Its
      identification has allowed the development of cellular and animal models; it has
      also permitted studies that identify both "manifesting" and "non-manifesting"
      DYT1 mutation carriers. These studies have expanded our understanding of clinical
      expression to include psychiatric symptoms and also have enabled imaging studies
      of endophenotypes. These advances provide a widened platform for future research.

PMID- 17017573
TI  - President to boost pride in nursing.

PMID- 17017575
TI  - Putting ageism in the past.

PMID- 17017574
TI  - We must address the lack of black nurses in senior NHS posts.

PMID- 17017576
TI  - Successful goal-setting.

PMID- 17017577
TI  - The role of statin therapy in preventing recurrent stroke.
AB  - Several interventions may be used to prevent recurrent stroke. The role of
      statins was recently clarified by a large double-blind trial comparing
      atorvastatin with placebo. This article outlines the study results and
      implications for practice.

PMID- 17017578
TI  - Mask ventilation.

PMID- 17017579
TI  - Managing inpatients who have personality disorders.
AB  - An increasing number of personality disorders services are being developed in
      medium secure settings. This specialised field is extremely challenging and
      professionals entering it must be equipped with the knowledge and skills to work
      effectively with this client group. This article aims to raise awareness of
      common issues and provide recognised and widely used management strategies.

PMID- 17017580
TI  - The safe use of children's toys within the healthcare setting.
AB  - Toys are classed as a potential source of infection because they can become
      contaminated with microorganisms from unwashed hands, body fluids or from
      children putting them in their mouths. Environmental audits by infection control
      teams have shown that toys kept in healthcare settings are often dirty and not
      subject to the recommended cleaning protocols.

PMID- 17017582
TI  - How to choose your nursing agency.

PMID- 17017581
TI  - The requirements for original doctoral research in nursing.
AB  - Clinical and academic doctorates (PhDs) demand an original piece of research.
      This article examines how to generate such research in nursing and proposes that
      it is not as elusive as it first appears.

PMID- 17017583
TI  - What must it be like to be a nursing student starting now?

PMID- 17017584
TI  - [Integration of the siblings of sick children].

PMID- 17017585
TI  - [Pediatric emergencies from the viewpoint of first aid].

PMID- 17017586
TI  - [Responsibility for confidentiality of health personnel is the foundation of
      patient trust].

PMID- 17017587
TI  - [Clothing and personal care over time].

PMID- 17017588
TI  - [Comment of the German Society of Pediatrics on the letter in
      Kinderkrankenschwester 25 (2006) no. 7 page 272 by Mrs. M. Vogenpohl].

PMID- 17017589
TI  - [Infusion therapy for premature and newborn infants: comparison of complication
      rates with and without in-line filters].

PMID- 17017590
TI  - [Study of German nursing education].

PMID- 17017591
TI  - [Sick children in need!].

PMID- 17017592
TI  - [The first vaccine for prevention of cervix cancer and other human papillomavirus
      related diseases gets a positive evaluation by the European Drug Authority].

PMID- 17017593
TI  - [Suckling calves with symptoms of swayback].
AB  - Within a 1-year period, three calves from the same herd developed ataxia of the
      hind limbs and urinary incontinence at about 6 months of age. Signs progressed
      and the calves were slaughtered 1-8 months after the onset of signs. The calves
      belonged to a suckling beef herd of 35 cattle. Blood samples from 11 cattle of
      different ages were collected and glutathione peroxidase and copper levels were
      measured. Glutathione peroxidase levels were below the normal range in all cattle
      and copper levels were below the normal range in 7 of ll cattle. Pathological
      examination of an affected calf revealed a Wallerian type of degeneration of
      myelinated nerve fibres in the lateral and ventral spinal cord tracts. In
      addition, the hepatic copper content was very low. Copper deficiency is a well
      known cause of swayback in young sheep and goats. To our knowledge, this is the
      first report of a possible association between a swayback-like syndrome and
      copper deficiency in calves.

PMID- 17017594
TI  - [Bluetongue in The Netherlands; description of the first clinical cases and
      differential diagnosis. Common symptoms just a little different and in too many
      herds].
AB  - For the first time Bluetongue (BT) has been diagnosed in the Netherlands. The
      clinical symptoms of BT on five farms during the first outbreak ever in the
      Netherlands are described. Fever and swollen sensitive coronets leading to
      reluctance to stand and walk were sometimes the first symptoms. Later lesions in
      the mouth occurred with foamy salivation and respiratory problems. In other cases
      a swollen head with swollen lips and foamy salivation were the first clinical
      signs. Also sudden death occurred. In the first sixteen confirmed cases morbidity
      and mortality were lower than described in outbreaks in other countries. Good
      collaboration between practitioners, specialists of the Animal Health Service (GD
      Deventer), and specialists of the Food and Consumer Product Safety Authority
      (VWA) and CIDC-Lelystad (Wageningen UR) led to a rapid notification and
      ultimately confirmation of the suspected diagnosis BT.

PMID- 17017595
TI  - [Billing rounds].

PMID- 17017596
TI  - [Policy note on animal welfare of the horse].

PMID- 17017597
TI  - ["Strict science and practicality." A century of the Dutch Central Veterinary
      Institute 1904-2004].

PMID- 17017598
TI  - [FIDIN antibiotic policy report 2005].

PMID- 17017599
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Silver dish and spoon, Royal Veterinary School].

PMID- 17017600
TI  - [KNMvD and Movir: Concerned as a general partner].

PMID- 17017601
TI  - ["An European problem in the making". Report on information evening about
      bluetongue].

PMID- 17017602
TI  - [Animal housing for large cow herds].

PMID- 17017603
TI  - ["A concerned veterinarian". Ton de Ruijter as chairman of the KNMvD: other
      people's turn].

PMID- 17017604
TI  - Chronic fatigue syndrome in young people: the spectrum and the myths.

PMID- 17017605
TI  - The NICE hypertension guideline update 2006: a welcome revision.

PMID- 17017606
TI  - Urinary tract injuries at caesarean section: prevention and management.
AB  - This article focuses on predisposing risk factors and mechanism of injury for
      urinary tract injuries at caesarean section. Tips on prevention of injury are
      followed by a detailed discussion of the management options when injury occurs.

PMID- 17017607
TI  - Botulinum toxin and the overactive bladder.
AB  - Botulinum toxin is now a treatment for many conditions. It is undergoing
      increasing use in several different unlicensed urological clinical situations
      which are outlined in this article. The article discusses the available evidence
      relating to its use, effectiveness and safety.

PMID- 17017608
TI  - Diagnosis and management of renal (ureteric) colic.
AB  - Renal (ureteric) colic is a common surgical emergency. It is usually caused by
      calculi obstructing the ureter, but about 15% of patients have other causes, e.g.
      extrinsic compression, intramural neoplasia or an anatomical abnormality. This
      review will focus on calculus-related renal or ureteric colic, its assessment and
      subsequent management.

PMID- 17017609
TI  - Otosclerosis: a review of aetiology, management and outcomes.
AB  - Otosdcerosis is an autosomal dominant condition affecting the temporal bone. It
      presents predominantly with deafness in a young population. This review looks at
      the aetiological theories, present treatment strategies and surgical outcomes of
      this condition.

PMID- 17017610
TI  - How to perform intrapartum fetal blood sampling.

PMID- 17017611
TI  - Diagnosing and managing depression.

PMID- 17017612
TI  - Applied anatomy of cricothyrotomy and tracheostomy.

PMID- 17017613
TI  - The intravenous urogram.

PMID- 17017614
TI  - Responsibilities of foundation year doctors.

PMID- 17017615
TI  - Achilles tendon rupture.

PMID- 17017616
TI  - So you want to be...a paediatrician.

PMID- 17017617
TI  - Endocrine therapies for sarcopenia in older men.
AB  - This review looks at new therapeutic developments for the increasingly recognized
      problem of sarcopenia. Increased adiposity and reduced lean body mass
      characterize ageing men. The potential therapeutic role of the growth
      hormone/insulin-like growth factor axis, androgen modulators and myostatin
      inhibition are discussed.

PMID- 17017618
TI  - Review of new guidelines for prophylaxis and treatment of MRSA infections.
AB  - A joint working party has produced evidence-based guidelines for the prophylaxis
      and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in
      the U.K. These guidelines will help clinicians choose appropriate therapy and
      point to areas where further research is needed. This review summarizes the main
      recommendations and discusses their implementation into clinical practice.

PMID- 17017619
TI  - Preregistration house officer skill and competency assessment through
      questionnaires.
AB  - In 1996 the University of Liverpool reformed its medical course from a very
      traditional lecture-based curriculum to an integrated problem-based learning
      curriculum. This article summarizes the results of questionnaires sent to both
      traditional and reformed curricula Liverpool graduates asking them to assess
      their competencies.

PMID- 17017620
TI  - Tonsillar haematoma presenting as a large oropharynx mass caused by toothbrush
      trauma.

PMID- 17017622
TI  - Sky's surgical screwups.

PMID- 17017621
TI  - Thyroid storm treated with intravenous methimazole in patients with
      gastrointestinal dysfunction.

PMID- 17017623
TI  - Thyrotoxic hypokalaemic periodic paralysis.

PMID- 17017624
TI  - A case of emphysematous pancreatitis.

PMID- 17017625
TI  - Modernising medical careers and the career framework.

PMID- 17017626
TI  - Dividing the spoils: the financial implications of getting divorced.

PMID- 17017627
TI  - How should postoperative pain in patients on long-term opioids be managed?

PMID- 17017628
TI  - Tooth bleaching--increasing patients' dental awareness.

PMID- 17017629
TI  - Ectopic eruption of the maxillary central permanent incisors and mandibular first
      permanent molars: report of an unusual case.
AB  - Ectopic eruption is a disturbance in which the tooth does not follow its usual
      course. Among its more important etiologic factors are macrodontism, shortened
      arch length, posterior positioning of the maxilla, atypical eruption angle, and
      genetic factors. This article reports a rare case of ectopic eruption of 4
      permanent teeth, maxillary central incisors and mandibular first molars, in a
      child aged 7 years and 11 months, in which the treatment consisted of extracting
      the maxillary primary central incisors and making an orthodontic intervention on
      the mandibular arch. A bilateral fixed appliance containing 2 hooks with loops, 1
      buccal and the other lingual, was placed on the mandibular primary first molars.
      The hooks were activated in a niche made of light-curing resin on the occlusal
      surface of the mandibular permanent molars, to bring about the distal drift of
      these teeth. After 6 months, complete eruption of the mandibular permanent molars
      occurred, and a slight displacement of the maxillary permanent central incisors
      toward the median line was noted. The importance of early, adequate treatment is
      discussed.

PMID- 17017630
TI  - Prospective clinical study of zirconia posterior fixed partial dentures: 3-year
      follow-up.
AB  - OBJECTIVES: The purpose of this prospective clinical cohort study was to
      determine the success rate of 3- to 5-unit posterior fixed partial dentures
      (FPDs) with zirconia frameworks after 3 years of function. METHOD AND MATERIALS:
      Forty-five patients in need of at least 1 FPD to replace 1 to 3 posterior teeth
      were included. The frameworks were produced by means of a prototype computer
      assisted manufacture system. They were milled with a precisely calculated
      increase in size out of presintered zirconia blanks and subsequently shrunk to
      the required size. Fifty-seven FPDs were cemented using either Variolink or
      Panavia TC cement. Clinical and radiographic examinations were performed at
      baseline, 12, 24, and 36 months after cementation. Statistical analysis was
      performed by descriptive statistics and the Kaplan-Meier survival analysis.
      Comparisons of probing depth, Plaque Index, and bleeding on probing between test
      (abutment) and control (contralateral) teeth were done with the McNemar test.
      RESULTS: Thirty-six patients with 46 FPDs were available for examination after 36
      months. No fractures occurred, rendering a 100% success rate of the zirconia
      frameworks. Seven FPDs had to be replaced because of biologic and technical
      problems. The survival rate, therefore, was 84.8%. Secondary caries was found in
      10.9% of the FPDs, and chipping of the veneering ceramic was found in 13.0%.
      There were no significant differences regarding the probing depth in test and
      control teeth. CONCLUSION: Zirconia frameworks demonstrated sufficient stability
      for replacement of posterior teeth. However, the high rates of technical problems
      should be reduced by further developments of the prototype processing technology.

PMID- 17017631
TI  - Randomized clinical trial on the efficacy of 2 over-the-counter whitening
      systems.
AB  - OBJECTIVE: The purpose of this clinical trial was to evaluate the efficacy of 2
      over-the-counter whitening systems: a liquid whitening gel (5.9% hydrogen
      peroxide, twice a day for 15 minutes), and a sodium chlorite-based whitening gel
      applied in a tray system (10 minutes twice a day). METHOD AND MATERIALS: Sixty
      volunteers (minimum shade A3 on 1 maxillary tooth) were selected to participate
      in this single-blind (examiner-blinded), single-center, 2-group trial. The
      subjects were randomly divided into 2 groups (n = 30 each) and instructed to
      bleach their teeth for 2 weeks. Efficacy was measured using the Vita Classical
      shade guide and a spectrophotometer at baseline, as well as after 2 weeks and 6
      months. RESULTS: For the subjectively measured tooth shades, improvement for
      maxillary canines was 2.03 +/- 3.67 tooth shades in group 1 and 1.08 +/- 2.19
      tooth shades in group 2 after 2 weeks; the maxillary incisors revealed a tooth
      shade improvement of 0.83 +/- 1.71 tabs in group 1 and 0.73 +/- 2.22 tabs in
      group 2 (P < .05, except maxillary incisors in group 2; t test). Objectively
      measured tooth shade scores revealed a change of 0 +/- 0.25 tooth shade tabs (P >
      .05). CONCLUSIONS: The bleaching gel containing hydrogen peroxide achieved a
      slight improvement, and the sodium chlorite-based bleaching gel achieved only a
      small tooth color improvement. Moreover, subjectively and objectively measured
      tooth shades revealed considerably different results in the clinical situation.

PMID- 17017632
TI  - Oral squamous cell carcinoma around dental implants.
AB  - It is well documented that oral squamous cell carcinoma (OSCC) is related to risk
      factors such as smoking and alcohol consumption as well as premalignant lesions
      and conditions such as leukoplakia, oral lichen planus (OLP), and previous
      malignancy of the upper respiratory system and gastrointestinal tract.
      Osseointegrated dental implants are rarely reported in association with OSCC.
      This article presents 2 cases of OSCC adjacent to dental implants in patients at
      risk for oral cancer--1 was a heavy smoker with OLP; the other had a history of
      previous oral and colon cancer. Six additional cases of malignancy adjacent to
      dental implants were retrieved from the literature; the majority of cases had at
      least 1 recognized risk factor for oral cancer. Although such cases are rarely
      reported, patients at risk for oral cancer, especially those with multiple
      existing risk factors, that present with failing dental implants should be
      thoroughly evaluated to rule out the presence of malignancy disguised as peri
      implant disease.

PMID- 17017633
TI  - Color compatibility of resin composites of identical shade designation.
AB  - OBJECTIVE: The aim of this study was to evaluate color compatibility of
      corresponding resin composite shades keyed to Vitapan Classical shade guide
      (Vita). METHOD AND MATERIALS: Twenty-one shades of 6 commercial resin composites
      were analyzed. Specimens (n = 5) were made as disks, 11 mm in diameter and 2 mm
      thick, using cylindrical molds. Specimens were polymerized according to
      manufacturers' suggestions using a light-curing unit. Data were collected using a
      spectrophotometer and analyzed using the appropriate color difference metric
      equations. A total color difference (deltaE*ab) greater than or equal to 3.7 was
      considered a mismatch. Analysis of variance and Fisher's probable least-squares
      difference (PLSD) test. intervals for comparison of means were calculated at the
      .05 level of significance. RESULTS: Mean deltaE*ab values among A2, B2, C2, and
      opaque A2 shade pairs were 4.4 (1.8), 7.3 (3.2), 5.6 (2.8), and 6.5 (1.8),
      respectively, while the mean color difference for all the pairs compared was 5.8
      (2.8). For A2 shades, deltaL*, deltaa*ab, and deltab*ab values ranged by 5.3,
      2.3, and 6.7, respectively. Corresponding values for B2 shades ranged by 10.5,
      2.2, and 11.5; 7.9, 2.2, and 4.3 for C2 shades; and 7.9, 1.4, and 4.4 for opaque
      A2 shades. Fisher's PLSD critical intervals for comparing deltaE*ab values among
      the shades and composite pairs were 0.07 and 0.15, respectively (P < .0001, power
      1.00). CONCLUSION: Overall, poor color compatibility of shade pairs of identical
      shade designation was recorded. The best color match was recorded for A2 shade
      pairs, followed by C2, B2, and opaque A2 shade pairs.

PMID- 17017634
TI  - Larva migrans in the oral mucosa: report of a case.
AB  - Larva migrans is a condition caused by subcutaneous or visceral migration of
      parasite larvae, usually Ancylostoma braziliense, and is characterized by
      pruriginous or serpiginous lesions. This article describes a case of larva
      migrans involving the oral mucosa in a 24-year-old woman.

PMID- 17017635
TI  - Alternative oral rehabilitation of children with hypodontia and conical tooth
      shape: a clinical report.
AB  - This case report outlines an alternative oral rehabilitation treatment of a 4
      year-old boy with hypodontia and conical tooth shape, which along with other
      characteristics led to a suspicious ectodermal dysplasia diagnosis. Diagnostic
      waxup and a silicone matrix formed the basis to the successful reconstruction of
      the anterior teeth with resin composite. Additionally, removable partial dentures
      were fabricated to improve esthetics and chewing ability. Positive psychologic
      influence of this alternative treatment on this patient is also discussed.

PMID- 17017636
TI  - Fracture strength of artificially aged 3-unit adhesive fixed partial dentures
      made of fiber-reinforced composites and ceramics: an in vitro study.
AB  - OBJECTIVE: The aim of this in vitro study was to examine the fracture strength of
      metal-free 3-unit adhesive fixed partial dentures (AFPDs) bonded to mandibular
      incisors. METHOD AND MATERIALS: Extracted human incisors were positioned in pairs
      in polymethyl methacrylate resin simulating a clinical anterior situation. Their
      lingual sides were prepared for adhesive retainers with surfaces and finishing
      lines in enamel. Eight 3-unit AFPDs were made on master casts per material
      system: Connect/belleGlass (Girrbach), StickNet (StickTech)/Sinfony (3M Espe),
      and Empress 2 (Ivoclar Vivadent). The dentures were bonded adhesively using the
      dual-curing system ED Primer/ Panavia F (Kuraray Europe) and aged by
      thermocycling (6,000 x 5 degrees C/55 degrees C H2O; 2 minutes each cycle) and
      mechanical loading (1.2 x 10(6) x 20 N with 1.66 Hz) in an artificial oral
      environment representing a wearing period of 5 years. The fracture strength was
      determined in a universal testing machine (UTM 1446, Zwick) at a speed of 1
      mm/min, applying the load buccoincisally on the pontics. The different forms of
      failure were described optically. Medians (25th/75th percentiles) of the fracture
      results were calculated. Statistical analysis was performed using Mann-Whitney U
      and Kruskal-Wallis tests (P < or = .05). RESULTS: Five StickNet/Sinfony AFPDs and
      7 Empress 2 restorations failed in the artificial oral environment. The remaining
      Empress 2 dentures showed the highest medians of fracture forces (339 [200/506]
      N) compared to Connect/belleGlass (257 [242/310] N) and StickNet/Sinfony (256
      [204/347] N). Statistical comparisons showed no significant differences.
      CONCLUSION: Only Connect/belleGlass and Empress 2 showed sufficient resistance
      against mastication

PMID- 17017637
TI  - Spontaneous fracture of genial tubercles: case report.
AB  - A case is presented of fractured genial tubercles, revealed by occlusal
      radiography, in a 63-year-old edentulous woman. Isolated fractures are a rare
      event that may present with pain and edema in the floor of the mouth. It occurs
      mainly in patients wearing a complete denture when the mandible is atrophied and
      the genial tubercles are hypertrophied. Only 11 case reports have been found in
      the English literature.

PMID- 17017640
TI  - [Birth and maternal addictive behaviors].

PMID- 17017641
TI  - [Care of the newborn with an addicted mother].

PMID- 17017642
TI  - [Multidisciplinary management of patients with addictive behavior in a maternity
      service].

PMID- 17017643
TI  - [Social work role at the maternity service in the Ecimud team].

PMID- 17017644
TI  - [Admitting mothers and their infants in neonatalogy].

PMID- 17017645
TI  - [Maternal lactation in mothers undergoing treatment with methadone substitution].

PMID- 17017646
TI  - [A tool to measure hospitalized children's satisfaction].

PMID- 17017647
TI  - [New intervention modes in social work with families].

PMID- 17017648
TI  - [3/7 The pediatric nurse's aide].

PMID- 17017649
TI  - Diversity, new realities and exciting opportunities.

PMID- 17017650
TI  - Ethical question of the month--June 2006. An ethicist's commentary on permitting
      deprivation research.

PMID- 17017651
TI  - Laboratory diagnosis of bovine tuberculosis in Canada for calendar year 2005.

PMID- 17017653
TI  - A field investigation of the use of the pedometer for the early detection of
      lameness in cattle.
AB  - The efficacy of the pedometer to predict lameness earlier than the appearance of
      the clinical signs in a herd of dairy cows was investigated by correlating
      pedometric activity (PA) with clinical cases of lameness. The computer program
      was set to identify cows with a reduction of 5% or more in PA compared with their
      own previous 10 days average; these animals were then examined for clinical
      lameness. At the same time, every lame cow was checked to see if and when its PA
      was reduced. Forty-six cows showed a reduced PA; 38 cases of lameness were
      identified by either a reduction in PA or clinical observation; of these, 21 lame
      cows (45.7%) showed a reduction in PA of 5% or more, 7 to 10 days prior to the
      appearance of clinical signs. This cohort comprised 55.3% of the lame cows. In
      92% of the lame cows identified by PA, the decrease was above 15%.

PMID- 17017652
TI  - Johne's disease in Canada Part I: clinical symptoms, pathophysiology, diagnosis,
      and prevalence in dairy herds.
AB  - Recent international developments in the area of infectious disease control and
      nontariff trade barriers, along with possible zoonotic concerns, have provoked a
      revival of interest in Johne's disease in Canada and elsewhere. The bacterium
      causing Johne's disease, Mycobacterium avium subspecies paratuberculosis, is
      distributed worldwide and causes chronic granulomatous enteritis, also known as
      paratuberculosis, in domestic and exotic ruminants, including cattle. The
      subclinical form of this disease results in progressive weight loss, reduced milk
      production, lower slaughter value, and premature culling, with possible impacts
      on fertility and udder health. Eventually, infection can lead to the clinical
      form that manifests as chronic diarrhea, emaciation, debilitation, and eventual
      death. Currently, available tests to detect infected animals produce many false
      negative results and some false-positives, particularly in subclinically infected
      animals, thus making their interpretation and utilization challenging in control
      programs. The objective of this 2-part review is to critically review the
      literature about Johne's disease in dairy cattle for bovine practitioners in
      Canada. Part I covers the clinical stages, pathophysiology, diagnosis, and
      prevalence of infection in Canada, while Part II discusses impacts, risk factors,
      and control programs relevant to Canadian dairy farms. By reviewing the
      scientific literature about Johne's disease, control of the disease could be
      pursued through informed implementation of rational biosecurity efforts and the
      strategic use of testing and culling.

PMID- 17017654
TI  - Survival of Salmonella Copenhagen in food bowls following contamination with
      experimentally inoculated raw meat: effects of time, cleaning, and disinfection.
AB  - There are concerns regarding the safety of feeding raw meat to household pets.
      This study demonstrated that Salmonella persists in food bowls that are
      inoculated with Salmonella-containing raw meat. Standard methods of cleaning and
      disinfection were minimally effective at eliminating Salmonella contamination.

PMID- 17017655
TI  - Inherited myopathy in a young Great Dane.
AB  - A 3-year-old, male Great Dane was evaluated for an 18-month history of
      progressive weakness. Histologic evaluation of muscle biopsies revealed distinct
      cytoarchitectural changes that were indistinguishable from the central "core
      like" structures previously described as central core myopathy in this breed.
      Clinical features of this inherited myopathy are described.

PMID- 17017656
TI  - Arthrodesis tarsocrural or tarsometatarsal in 2 dogs using circular external
      skeletal fixator.
AB  - An external fixation technique, using a circular fixator, to obtain arthrodesis
      was evaluated in 2 dogs with infected open lesions and soft tissue damage. In
      both cases, articular cartilage was curetted, and devitalized bone and necrotic
      soft tissue were removed. No bone graft was used. The wounds were maintained open
      and the dogs received postoperative antibiotic therapy. The arthrodesis site was
      compressed progressively as needed. Infection was eradicated and bony union was
      obtained in both dogs. It was concluded that the use of a circular fixator is an
      effective method to achieve arthrodesis.

PMID- 17017657
TI  - Clinical diagnosis of uterine didelphia in Ayrshire heifer.
AB  - A 24-month-old Ayrshire heifer was referred because of infertility. A clinical
      diagnosis of uterus didelphys was established after a complete genital
      examination before the animal was culled from the herd.

PMID- 17017658
TI  - Copper deficiency in yaks on pasture in western China.
AB  - The clinical signs of a disorder in yaks (Bos grunniens), known locally as
      "swayback ailment," in the Qing Hai-Tibetan Plateau are described. The purpose of
      this study is to investigate the possibility that swayback ailment is iron (Fe)
      induced copper (Cu) deficiency. The mean concentrations of Cu in soil and forage
      from affected areas and unaffected areas are similar and within the normal
      ranges. The mean concentrations of Cu in blood and hair from the affected yaks
      was significantly lower (P < 0.01) than that in unaffected yaks. The mean
      concentrations of Fe in soil and forage were significantly higher (P < 0.01) in
      affected than in unaffected areas. Affected yaks showed a hypochromic microcytic
      anemia and a low level of ceruloplasmin. Oral administration of copper sulphate
      prevented and cured the disease. We conclude that "swayback disorder" of yaks is
      caused by secondary Cu deficiency, mainly due to the high Fe content in forage.

PMID- 17017659
TI  - Unilateral congenital elbow luxation in a dachshund.
AB  - Congenital elbow luxation was diagnosed in a 12-week-old, intact male, dachshund
      with a lateral elbow prominence and mild lameness of the right forelimb. Closed
      reduction of the radial head, ulnar ostectomy, and external stabilization of the
      joint were performed. Function was returned to the limb, but radial head and
      ulnar subluxation persisted.

PMID- 17017660
TI  - The CVMA Animal Welfare position statements: a general analysis.

PMID- 17017661
TI  - Model of practice excellence--budgeting with New Hamburg Veterinary Clinic.

PMID- 17017662
TI  - Multifocal bullous retinopathy of coton de Tulear dogs.

PMID- 17017663
TI  - Acute effects of radiation treatment: skin reactions.

PMID- 17017664
TI  - ESHAP salvage therapy for refractory and relapsed non-Hodgkin's lymphoma: a
      single center experience.
AB  - BACKGROUND: The ESHAP chemotherapy regimen, that is, the combination of the
      etoposide, methylprednisolone, high-dose cytarabine and cisplatin, has been shown
      to be active against relapsing or refractory non-Hodgkin's lymphoma (NHL) in
      previous therapeutic trials. We attempted to determine whether ESHAP therapy
      would be effective and well-tolerated in Korean patients. METHODS: Twenty two
      patients with refractory or relapsed NHLs (all aggressive types) were enrolled in
      this study. We retrospectively evaluated the treatment response, the survival
      rate and the time to progression. RESULTS: Six patients (27.3%) attained complete
      remission and eight patients (36.4%) attained partial remission. The overall
      response rate was 63.6%. The median survival duration was 15.5 months (95%
      confidence interval; 10.7 to 20.3 months), and the median duration of the time to
      progression was 8.3 months (95% confidence interval; 0.3 to 16.3 months).
      Myelosuppression was the major toxicity, but severe neutropenia or
      thrombocytopenia was rare, and renal toxicity was also infrequent. CONCLUSIONS:
      ESHAP regimen is effective in Korean patients suffering with relapsed or
      refractory NHLs, but a more effective salvage modality is needed because of the
      short duration of remission and the insignificant impact on long-term survival.

PMID- 17017665
TI  - Intravenous itraconazole vs. amphotericin B deoxycholate for empirical antifungal
      therapy in patients with persistent neutropenic fever.
AB  - BACKGROUND: Amphotericin B dexoycholate is currently the standard empirical
      antifungal therapy for neutropenic patients with hematologic malignancies and who
      also have persistent fever that does not respond to antibacterial therapy. The
      antifungal triazoles offer a potentially safer and effective treatment
      alternative to Amphotericin B dexoycholate. METHODS: We assessed the efficacy and
      safety of intravenous itraconazole, as compared with the efficacy and safety of
      amphotericin B deoxycholate, as an empirical antifungal therapeutic agent in a
      matched case-control clinical trial from June 2004 to August 2005. RESULTS:
      Efficacy was evaluated in 96 patients (48 received itraconazole and 48 received
      amphotericin B deoxycholate) and all the patients who received the study drugs
      were evaluated for safety. The baseline demographic characteristics were well
      matched. The overall success rates were 47.9% for itraconazole and 43.8% for
      amphotericin B deoxycholate (% difference: 4.1% [95% confidence interval for the
      difference: -15.8 to 24]), which fulfilled the statistical criteria for the non
      inferiority of itraconazole. The proportions of patients who survived for at
      least seven days after discontinuation of therapy or who were prematurely
      discontinued from the study were not significantly different between the two
      groups. The rates of breakthrough fungal infections and resolution of fever
      during neutropenia were similar in both groups. More patients who received
      amphotericin B deoxycholate developed nephrotoxicity, hypokalemia or infusion
      related events than did those patients who received itraconazole (nephrotoxicity:
      16.7% vs. 1.8%, hypokalemia: 66.7% vs. 24.6%, and infusion-related events: 41.7%
      vs. 3.5%, respectively). CONCLUSIONS: Intravenous itraconazole is as effective as
      amphotericin B deoxycholate and it is generally better tolerated than
      amphotericin B deoxycholate when it is given as empirical antifungal therapy for
      Korean patients with persistent neutropenic fever.

PMID- 17017666
TI  - Benign pulmonary metastasizing leiomvomatosis: case report and a review of the
      literature.
AB  - The authors report here on a case of a nearly asymptomatic 51-year-old Korean
      woman who was found to have diffuse, multiple nodules of the lungs on a routine
      chest radiograph. She had undergone hysterectomy 16 years previously for uterine
      myoma. An open lung biopsy revealed tumor that was composed of interlacing
      bundles of spindle cells with cigar shaped nucleus and eosinophilic myofibrils in
      the cytoplasm; consistent with multiple leiomyomas. The stains for SMA, desmin,
      MSA and Ki-67 were positive and the stain for c-kit was negative. The other
      stains for estrogen and progesterone receptor were positive. During the open lung
      biopsy procedure, all the nodules were excised. We report here on an interesting
      case of benign metastasizing leiomyoma (BML) in 51-year-old patient. To the best
      of our knowledge, this case showed the longest period of clinical progression in
      Korea. This is also one of a few cases in which curative excision was
      successfully performed.

PMID- 17017667
TI  - Photodynamic therapy in early lung cancer: a report of two cases.
AB  - Photodynamic therapy (PDT) that is based on the science of photochemistry has
      been recognized as a lung sparing local therapeutic modality that can achieve
      remarkable responses. It is an alternative treatment for early stage lung cancer
      patients who have poor lung function or multiple sites of cancer. Recently we
      treated a 70-year-old man who presented with squamous carcinoma in situ at a
      previous pneumonectomy site, and a 64-year-old man with a newly developed
      secondary superficial lung cancer, with PDT. There were no complications related
      to the procedure. Both patients had poor lung function due to prior lung cancer
      surgery. Clinical and histological complete remissions were achieved without any
      evidence of recurrence during 30 months of follow-up in both patients.

PMID- 17017668
TI  - Two cases of interstitial pneumonitis caused by rituximab therapy.
AB  - Rituximab, a chimeric monoclonal antibody directed against CD20, has become a
      part of the standard therapy for patients with non-Hodgkin's lymphoma either in
      combination with other drugs or as a single agent. The CD20 antigen is expressed
      on 95% of B-cell lymphoma cells and normal B-cells but, is not found on precursor
      B-cells or stem cells. Rituximab is now approved for patients with diffuse large
      B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide,
      doxorubicin, vincristine and prednisone) or patients with follicular lymphoma who
      have failed first line chemotherapy. The monoclonal antibody is generally well
      tolerated. Most of the adverse events are infusion-associated, mild to moderate
      non-hematological toxicities. Severe respiratory adverse events have been
      infrequent. Here, we report two patients with non-Hodgkin's lymphoma in whom
      interstitial pneumonitis developed with rituximab therapy.

PMID- 17017669
TI  - Transluminal removal of a fractured and embolized indwelling central venous
      catheter in the pulmonary artery.
AB  - Vascular catheters are associated with complications such as infection,
      thrombosis and stenosis. The embolization of a venous catheter fragment is a rare
      complication. A 39-year-old woman underwent placement of a totally implantable
      venous access device for chemotherapy to treat a recurrent liposarcoma of the
      left thigh. The "pinch-off sign" was noted on a routine chest X-ray but that was
      ignored. Three-months after implantation of the intravenous access device, the
      indwelling central catheter was fractured and embolized to the pulmonary trunk.
      The catheter in the pulmonary trunk was successfully removed through a
      percutaneous femoral vein approach using a pigtail catheter and goose neck snare.

PMID- 17017670
TI  - Small cell carcinoma of the kidney.
AB  - Up to 5% of all small cell carcinomas develop at extrapulmonary sites. Primary
      small cell carcinomas originating in the kidney are extremely rare neoplasms.
      Here we report a case of primary small cell carcinoma of the kidney. A
      nephrectomy was performed on a 52-year-old female patient to remove a large tumor
      located in the right kidney. The histology and immunohistochemistry of the
      resected tumor revealed a pure small cell carcinoma with invasion into the renal
      capsule. The patient received postoperative adjuvant chemotherapy with etoposide
      and cisplatin. The patient has been monitored with regular check ups and remains
      stable with no recurrence at 28 months after the initial diagnosis.

PMID- 17017671
TI  - High-grade hepatic mucosa-associated lymphoid tissue (MALT) lymphoma probably
      transformed from the low-grade gastric MALT lymphoma.
AB  - The Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first described
      in 1983, is known to be caused by chronic Helicobacter pylori (HP) infection,
      which triggers lymphoid infiltration and formation of organized lymphoid tissue.
      In approximately two thirds of cases of MALT, the lymphoma has been observed to
      regress after treatment of H. pylori infection; this provides strong evidence of
      a causative role of HP in the etiology of MALT. We report a case of a 67-year-old
      female patient with a high-grade MALT lymphoma of the liver; this occurred six
      years after complete remission of a low-grade gastric MALT lymphoma and after
      complete eradication of H. pylori. there was no recurrence of the previous low
      grade gastric MALT lymphoma. Based on radiological and pathologic findings, the
      high-grade MALT was considered to result from transformation of the low-grade
      gastric MALT lymphoma.

PMID- 17017672
TI  - A case of benign metastasizing leiomyoma with multiple metastasis to the soft
      tissue, skeletal muscle, lung and breast.
AB  - Benign metastasizing leiomyoma (BML) is composed of well-differentiated smooth
      muscle cells and dense connective tissue. BML affects middle-aged women who have
      had previous hysterectomies due to a histologically benign-appearing uterine
      leiomyoma. We report here on a case of BML from the uterine leiomyoma in a 39
      year-old woman that involved the soft tissues, skeletal muscles, lungs and
      breasts. She underwent a hysterectomy for the uterine leiomyoma, double
      oophorectomy for hormonal ablation and lung wedge resection to confirm the
      diagnosis. The microscopic findings of the breast and lung tumor were similar to
      those of the benign uterine leiomyoma. Therefore, we consider that these lesions
      were breast and pulmonary metastases of the uterine leiomyoma. We report here on
      a rare case of benign metastasizing uterine leiomyoma that involved the soft
      tissue, skeletal muscles, lungs and breasts, and we include a review of the
      relevant literature.

PMID- 17017673
TI  - A case of nonsecretory multiple myeloma with atypical imaging features.
AB  - Multiple myeloma usually shows homogeneous enhancement on contrast-enhanced
      Magnetic Resonance imaging (MRI), and is accompanied by a monoclonal gammopathy
      in serum or urine. We report a case of nonsecretory myeloma, the diagnosis was
      difficult due to the absence of a monoclonal gammopathy and the presence of
      atypical imaging features.

PMID- 17017674
TI  - Hepatic subcapsular steatosis in a diabetic CAPD patient receiving
      intraperitoneal insulin.
AB  - Hepatic subcapsular steatosis is a rare and specific form of fatty change in the
      liver. It is a unique finding in diabetic patients receiving continuous
      ambulatory peritoneal dialysis (CAPD) and intraperitoneal insulin treatment.
      Intraperitoneal administration of insulin causes a unique pattern of fatty
      infiltration in the subcapsular location of the liver. Here we report a case of
      hepatic subcapsular steatosis in a diabetic CAPD patient who received
      intraperitoneal insulin. A 46-year-old diabetic woman on CAPD presented with
      general weakness. The patient received a total amount of 110 units of regular
      insulin via intraperitoneal and subcutaneous injection. Her initial blood
      chemistry showed increased serum lipid and liver enzyme profiles. Abdominal CT
      scan images and MRI revealed characteristic findings consistent with hepatic
      subcapsular steatosis. We assumed that the cause was CAPD and concomitant
      intraperitoneal insulin treatment; therefore, the patient was switched from CAPD
      to hemodialysis (HD) and began to receive insulin subcutaneously. Two months
      after the beginning of HD, the hepatic subcapsular steatosis completely resolved.

PMID- 17017675
TI  - A case of multiple organ failure due to heat stoke following a warm bath.
AB  - Heat stroke is a potentially fatal disorder that's caused by an extreme elevation
      in body temperature. We report here an unusual case of multiple organ failure
      that was caused by classical, nonexertional heat stroke due to taking a warm bath
      at home. A 68 year old diabetic man was hospitalized for loss of consciousness.
      He was presumed to have been in a warm bath for 3 hrs and his body temperature
      was 41degrees C. Despite cooling and supportive care, he developed acute renal
      failure, disseminated intravascular coagulation (DIC) and fulminant liver
      failure. Continuous venovenous hemofiltration was started on day 3 because of the
      progressive oligouria and severe metabolic acidosis. On day 15, septic ascites
      was developed and Acinetobacter baumanii and Enterococcus faecium were isolated
      on the blood cultures. In spite of the best supportive care, the hepatic failure
      and DIC combined with septic peritonitis progressed; the patient succumbed on day
      25.

PMID- 17017676
TI  - Tachycardiomyopathy induced by ventricular premature complexes: complete recovery
      after radiofrequency catheter ablation.
AB  - Ventricular premature complexes (VPCs) are known to be one of the most benign
      cardiac arrhythmias when they occur in structurally normal hearts. We experienced
      a 32-year old man who presented with dyspnea, palpitations and very frequent VPCs
      (31% of the total heart beats). Echocardiography revealed a dilated left
      ventricle (LV 66 mm at end-diastole and 57 mm at end-systole) and a decreased
      ejection fraction (34%). Very frequent VPCs had been detected 10 years previously
      and he underwent a failed radiofrequency catheter ablation (RFCA) procedure at
      that time. The patient had been treated with heart failure medications including
      betablockers, ACE inhibitors and spironolactone for the two most recent years.
      Six months after we eliminated these VPCs with a second RFCA procedure, the heart
      returned to normal function and size. Long standing and very frequent VPCs could
      be the cause of left ventricular dysfunction in a subset of patients who suffer
      with dilated cardiomyopathy, and RFCA should be the choice of therapy for these
      patients.

PMID- 17017677
TI  - [Treatment of epithelial ovarian cancer].
AB  - Epithelial ovarian cancer is the most lethal gynecological cancer among women.
      The median age at diagnosis is 63 years. The vast majority of patients present
      with advanced disease and require a combination of cytoreductive surgery and
      adjuvant chemotherapy. Important features that determine the outcome of treatment
      include the stage of disease, hystological type, grade and the size of the
      residual tumour after initial surgery. Current guidelines recommend that standard
      first-line chemotherapy should include a platinum-based regimen with paclitaxel.
      Despite the combined therapy, over 50% of all the patients has relapse. Relapsed
      ovarian cancer is incurable, however chemotherapy can improve quality of life and
      survival. Currently, there is no worldwide accepted standard treatment for
      patients with platinum-refractory ovarian cancer. Docetaxel, topotecan,
      gemcitabine, pegylated liposomal doxorubicin, etoposide and tamoxifen can be used
      in this group. However response duration rarely exceeds 12 months.
      Intraperitoneal chemotherapy, gene therapy, immunotherapy, signal transduction
      inhibitors (trastuzumab) and angiogenesis inhibitors (bevacizumab) are all
      potential future therapies, and are being investigated in ongoing clinical
      research. In this publication authors review the literature of current treatment
      options in epithelial ovarian carcinoma.

PMID- 17017678
TI  - [Folic acid supplementation for pregnant women in Hungary].
AB  - INTRODUCTION: Neural tube defects are common major congenital anomalies. Folic
      acid supplementation has been shown to reduce the incidence of neural tube
      defects. In 2003, incidence of neuroblastoma has decreased with 60% in Canada as
      a result of enriched cereal grain flours with synthetic folic acid. The aim of
      this study was to investigate the effect of the practice of the folic acid intake
      by pregnant women (based on the Hungarian recommendation) to the incidence of
      neural tube defects and neuroblastoma. METHODS: The practice of folic acid
      supplementation was examined by questionnaires filled according to the
      documentation of health visitors. The data were worked up by computer. The
      incidence of neural tube defect was obtained from the data of the Hungarian
      Congenital Anomalies Registry, however, the data of National Health Insurance
      Company are also given. The incidence of neuroblastoma was the data of the
      Hungarian Pediatric Tumor Registry. Regular folic acid intake has been
      recommended to pregnant women in Hungary, since the eighties of the last century.
      An official protocol had been released by the Obstetric and Gynecologic
      Professional Board in 1997. In this paper, the authors report the Hungarian
      pregnant women's folic acid intake in years of 2001, 2002 and 2003. These years
      were chosen, because according to the data of the Hungarian Pediatric Cancer
      Registry 45% of the neuroblastoma cases are less than 1 year old, and 45% of them
      are 1-5 years old at the time of diagnosis. The authors succeeded to collect the
      data from 95% of the pregnant women during these years (271,748 women). RESULTS:
      Based on the statistical analysis of the collected data, 69% of the pregnant
      women were regularly taking folic acid products in Hungary, however, the dose of
      the daily intake was below 5 mg. 93% of the pregnant women started the folic acid
      intake after their 7th weeks of pregnancy The incidence of neural tube defects
      was constant, and the incidence of neuroblastoma slightly increased during the
      above mentioned period. CONCLUSIONS: This work highlighted that, the folic acid
      intake to prevent neural tube defects was started too late, because the formation
      of neural tube is finished on 28. day of pregnancy. 85% of the pregnant women
      used less amount of folic acid than 5 mg/day. The increasing number of planned
      pregnancies would allow to start folic acid intake earlier. However, based on
      international experience, the enrichment of cereal grain flours with synthetic
      folic acid could provide optimal results.

PMID- 17017679
TI  - [Bologna process and higher health education in Europe].
AB  - AIM: Introduction of the two cycles (Bachelor/Master) system represents sensitive
      aspect of the implementation of the Bologna process into higher health education.
      The authors used the methods of evidence based medicine to analyse available
      documents on the implementation of the Bologna process into the education of
      health sciences. METHODS: Electronic search in the closed MEDLINE and open
      Internet databases. RESULTS: Electronic data collection resulted in so-called
      country reports (n=47) and in professional statements (n=7) of health education
      bodies. Majority of the country reports (n=26) did not mention at all the
      peculiar position of health education within the Bologna process. Many country
      reports stated with (n=8) or without (n=9) explanation that health sciences
      should be excluded from the introduction of the two educational cycles system.
      Only 4 country reports discussed future conditions and possibilities of
      introducing the two cycles system into higher health education; the German
      country report definitely declared that the two cycles educational system may be
      introduced also into health education. The seven statements of professional
      health educational bodies (including an ad hoc committee of the Hungarian medical
      faculties) did not support the introduction of the two cycles system into health
      education. The low demand for health professionals with Bachelor (i.e.
      unfinished) degree was repeatedly mentioned as strong argument for not
      introducing the two cycles system into health education. It should be noted,
      however, that the process of introducing the two cycles system has began: recent
      survey of EUA (European University Association) indicates that in three countries
      (Denmark, Flanders and Switzerland) the introduction in under current discussion.
      CONCLUSION: Among the principles of the Bologna process, the introduction of the
      two cycles system has not gain acceptance in the higher health education in
      Europe. However, most documents firmly support the introduction of other elements
      of the Bologna process (comparable degrees, system of credits, promotion of
      mobility of students and tutors, quality control, life long learning).

PMID- 17017680
TI  - [Neurovesical dysfunction in children with anorectal malformations].
AB  - Chronic renal failure remain the most significant cause of morbidity and
      mortality in patients with anorectal malformation. The urological anomalies
      associated with anorectal malformations are not only anatomical, but also
      functional, the latter being related to congenital neurovesical dysfunction. The
      neurovesical dysfunction found in children with anorectal malformations results
      from a possible association with spinal dysraphism. The authors carried out
      urodynamic evaluation on 6 patients operated on for anorectal malformation by
      posterior sagittal anorectoplasty. 3 children had normal bladder function, but 3
      had neurovesical dysfunction (1 unstable bladder, 2 neuropathic bladder). It is
      concluded that in patients with anorectal malformations urodynamic investigations
      should be performed as a routine investigation of the urinary tract.
      Consequently, patients with lower urinary tract dysfunction should receive prompt
      treatment, including clean intermittent catheterization, to prevent or reduce
      secondary urologic morbidity, especially loss of renal function.

PMID- 17017681
TI  - [Stromal tumor of the stomach causing life-threatening arterial bleeding].
AB  - Stromal tumors of the gastrointestinal tract are rare mesenchymal neoplasms. The
      majority of them are appearing in the stomach: their quite common first
      manifestation is bleeding. The authors report a case of polypoid gastric GIST
      causing severe bleeding which needed urgent surgical intervention and partial
      resection of the stomach. Although histological analysis of the tumor revealed
      low proliferation rate, the urgent operation did not result in a complete
      eradication of the neoplasm, thereby our patient needs further follow-up and
      treatment.

PMID- 17017682
TI  - [Can we call the preventive part of genomic medicine as genomic epidemiology?].

PMID- 17017683
TI  - [Istvan Zsako, psychiatrist and medical historian].

PMID- 17017684
TI  - [Training of physicians and pharmacists in the Byzantine Empire].

PMID- 17017685
TI  - Perioperative cardiac risk stratification and modification in abdominal aortic
      aneurysm repair.
AB  - Cardiovascular complications are important causes of morbidity and mortality
      following vascular surgery. Adequate preoperative risk assessment and
      perioperative management may modify postoperative mortality and morbidity and
      improve long-term prognosis. The objective of this review is to examine the
      present day knowledge regarding the preoperative evaluation and perioperative
      management of patients undergoing noncardiac surgery, focusing specifically on
      abdominal aortic aneurysm (AAA) repair. Clinical markers combined with ECG and
      surgical risk assessment can effectively divide patients in a truly low-risk,
      intermediate and high-risk population. Low-risk patients can probably be operated
      on without additional cardiac testing. Notably, due to the surgical risk, AAA
      patients are never low-risk patients. Intermediate-risk and high-risk patients
      are referred for cardiac testing to exclude extensive stress induced myocardial
      ischemia, as beta-blockers provide insufficient myocardial protection in this
      case and preoperative coronary revascularization might be considered. Whether
      patients at intermediate risk without ischemic heart disease should be treated
      with statins and/or beta-blockers is still controversial. In high-risk patients,
      it is strongly advised to administer beta-blockers with heart rate determined
      dose adjustment, while the effects of preoperative revascularization remain
      subject to debate.

PMID- 17017686
TI  - Timing of complications during carotid artery stenting. How can they be
      predicted?
AB  - Carotid artery stenting (CAS) is becoming increasingly common for the treatment
      of carotid stenosis. Accumulating data, but not randomised data, suggest that CAS
      has promising efficacy in preventing stroke with an acceptable rate of procedure
      related complications when compared to carotid endarterectomy (CEA). However, CAS
      procedures can carry a risk of non-negligible complications such as cerebral
      embolization, cerebral hemorrhage, severe hypotension and bradycardia. These may
      occur after the first 24 hours. Lessons may be learned from the timing of
      occurrence of CAS adverse events. The most severe neurological complications are
      generally due to embolism and occur intraprocedurally especially during catheter,
      wire or sheath manipulation in the aortic arch and common carotid. These strokes,
      obviously, cannot be prevented by using cerebral protection devices and enhance
      the importance of an appropriate learning curve that includes proper material
      choice, patient selection, good technique and the skill of "know when to quit".

PMID- 17017687
TI  - Distal venous patch improves results in PFTE bypasses to tibial arteries.
AB  - In recent years, the management of limb-threatening ischemia has involved the use
      of distal bypasses to vessels beyond the popliteal trifurcation. Excellent
      patency rates and limb salvage data are achieved through the use of autologous
      long saphenous vein. However, an increasing number of patients in need of tibial
      bypass do not have adequate saphenous vein due to previous procedures,
      thrombophlebitis, or inadequate vein. In such cases alternative conduits have
      been proposed including lesser saphenous vein, arm vein, composite veins,
      composite vein with polytetrafluoroethylene (PTFE), and PTFE with or without a
      distal arteriovenous fistula. Unfortunately these alternative conduits have not
      resulted in equivalent results when used for distal bypass to tibial arteries.
      Several authors have reported upon the use of venous tissue at the distal
      anastomosis in the form of cuffs, collars, and boots to improve the results of
      prosthetic grafts in this challenging patient population. These techniques have
      been proposed as an option for revascularization in patients without adequate
      saphenous vein in an attempt to obtain limb salvage. The purpose of this review
      is to examine some of those techniques and focus on distal vein patch
      configuration with its perceived advantages and drawbacks.

PMID- 17017688
TI  - Laryngeal dysfunction after thyroid surgery: diagnosis, evaluation and treatment.
AB  - Because of the close anatomical relationships between thyroid gland and laryngeal
      nerves, sensory-motor impairment of the laryngeal functions is a well known
      possible complication of thyroid surgery. Laryngeal nerve paralysis can present
      with various and often associated symptoms like dysphagia, aspiration, voice
      alteration or dyspnea. Several examination procedures are mandatory to perform a
      complete neuro-laryngeal evaluation: rigid and flexible video-stroboscopy will
      assess the abductor, adductor and tensor functions in breathing, sniffing,
      talking and eventually singing tasks. Laryngeal electromyography (LEMG), despite
      its technical difficulties, brings valuable objective and pronostic informations.
      Aerodynamic assessment of voice production and objective acoustic voice
      evaluation are important for patients' follow-up, especially for voice
      professionals like teachers and singers. Treatment of laryngeal sensory-motor
      nerve paralysis can be conservative, with the help of speech therapy. Early
      surgical treatment is indicated in cases with severe functional problems like
      aspiration pneumonia, disabling breathy hypophonia, ineffective cough, disabling
      dyspnea. Surgical therapy at 6 to 9 months after injury is indicated in patients
      who demonstrate evidence of denervation or little activity on LEMG and have a
      poor response to a reasonable trial of speech therapy. Many surgical procedures
      are available. Depending on the type of neuro-laryngeal deficit, the main and
      more widely used techniques are: injection laryngoplasty, medialization
      thyroplasty, arytenoid adduction, arytenoidopexy, crico-thyroid approximation,
      endoscopic laser cordotomy and re-innervation procedures.

PMID- 17017689
TI  - Evolution during half a century of the results of digestive surgery in geriatric
      patients. A review of the literature, experience at C.H.U. Brugmann and the
      medium term outlook.
AB  - The undertaking of complex and major surgical procedures on frail elderly
      patients with multiple disorders has always been and still remains a
      controversial and enigmatic issue. At the same time, in an increasingly ageing
      society, the need for such procedures will extend and patients will expect a more
      favourable outcome. Surgery in old age will, therefore, pose an ongoing
      challenge. With better anaesthetic management, surgical techniques and
      comprehensive geriatric assessment, the overall results for all surgery have
      improved remarkably over the last few decades. Stringent pre-operative assessment
      and rigorous post-operative care have achieved a significant reduction in
      mortality and morbidity; surgery has become a lot safer.

PMID- 17017690
TI  - Quality of life after hip fracture surgery in the elderly.
AB  - As the world population ages, the prevalence of osteoporosis and the incidence of
      hip fractures will increase dramatically, being responsible for an increase of
      the health expenditure. On the other hand, there is the inescapable fact of
      scarcity creating the necessity of making difficult choices with regard to the
      allocation of human resources. So the question remains: should we carry on
      investing an important part of our health expenditure for the treatment of hip
      fractures in elderly people? To answer this statement, we compared 384 hip
      fracture patients of 70 years and older treated in our department between 1978
      and 1983 with 1102 patients treated between 1998 and 2003. Both groups had a
      prospective follow-up of at least one year. There were no statistically
      significant differences: mortality rate 24% vs. 23%; good functional outcome 82%
      vs. 73%; and home going rate 60% vs. 66%. The factors influencing these results
      were studied. So we can conclude: The number of hip fractures treated nowadays
      has increased compared with twenty years ago; There is no significant improvement
      in mortality, nor in quality of life; Age is not a contraindication for hip
      fracture surgery.

PMID- 17017691
TI  - Does retrojugular route for carotid endarterectomy increase the risk of internal
      jugular vein thrombosis?
AB  - Two different approaches are available to perform carotid endarterectomy: the
      traditional antejugular or the retrojugular route. With retrojugular route,
      direct access to the carotid arteries necessitates median retraction and often
      collapse of the internal jugular vein (IJV). Therefore, we have prospectively
      evaluated the potential incidence of IJV thrombosis.

PMID- 17017692
TI  - Surgical breast lesions in adolescent patients and a review of the literature.
AB  - BACKGROUND/PURPOSE: Breast disease in adolescence is uncommon, with most
      presenting lesions being benign. Breast lesions in adolescent patients are
      discussed in this article with a review of world literature. PATIENTS AND
      METHODS: The clinical records of 30 patients operated upon for breast lesions in
      our hospital during 18 years were reviewed. RESULTS: There were 25 female and
      five male patients, ranging in age from 16 years. Twenty-five female patients
      were operated on for breast mass and/or discharge, and five male adolescents were
      operated on for gynaecomastia. The most frequent (n = 27) complaint was palpation
      of mass in the breast. The most common histologies were fibro-adenoma (n = 14)
      and gynaecomastia (n = 5). The average duration of pre-operative symptoms was 2.9
      months for fibro-adenoma, 1.6 years for gynaecomastia (extremes 2 days to 1
      year). Nipple discharge was observed in three patients. Average diameters of
      palpable masses were 2.9 cm for fibro-adenomas and 5 cm for gynaecomastia.
      Lesions were excised surgically in all patients. Masses diagnosed as fibro
      adenomas in the pre-operative period were reported upon pathological examination
      to be precancerous lesions such as cystosarcoma phylloiedes, juvenile fibro
      adenoma, solitary intraductal papilloma, tubular adenoma and juvenile papilloma.
      One postoperative wound infection and one recurrence of fibro-adenoma was seen.
      CONCLUSION: The most frequently encountered breast masses were fibro-adenomas.
      These lesions are mostly benign in nature and can be treated conservatively but
      the possibility of precancerous lesion should be considered during follow-up.

PMID- 17017693
TI  - Operative approach in traumatic injuries of the duodenum.
AB  - BACKGROUND: The management of duodenal traumas remains controversial. The
      experience of Ankara Numune Training and Research Hospital Emergency Surgery
      Department with duodenal injuries during a 10-year period was analyzed to
      identify trends in operative management and sources of duodenum-related morbidity
      and mortality. METHODS AND RESULTS: Between 1994 and 2003, 1799 patients with
      blunt abdominal trauma were operated on and the incidence of duodenal trauma was
      2.8% (50 patients). The injuries were penetrating in 31 (62%) patients and blunt
      in 19 (38%). Primary repair (PR) of injury was performed in 24 (48%) patients,
      primary repair and tube duodenostomy (PRTd) in 8 (16%) patients, complex repair
      (CR) in 11 (22%) patients, and exploration only without a duodenal procedure in 5
      (10%) patients. Two of the patients died during laparotomy. The mortality rate
      was 12% and the incidence of duodenum-related morbidity was 12%. The overall
      morbidity rate was 40% (20 patients). The most commonly injured portion of the
      duodenum was DII (58%), and the most frequent cause of duodenum-related and
      overall morbidity in our series was Grade III duodenal injury. CONCLUSION: Our
      experience suggests that the use of primary repair in grade III injury may be
      associated with higher duodenum-related morbidity. Our recommendation is to use
      complex repair for grade III duodenal injuries.

PMID- 17017694
TI  - Intussusception in adults.
AB  - To review clinical, radiological and histopathological findings of adult
      intussusception and its management, 18 adult patients who had been treated
      surgically because of intussusception were reviewed. Of the patients, 5 (27.8%)
      had idiopathic intussusceptions, while the other 13 (72.2%) had a definable
      intraluminal pathology. The site of the intussusception was more common in the
      small bowel (83.3%) than the colon (16.7%). Ultrasonography and computed
      tomography were successful in demonstrating "target lesion" in 80% and 75%
      respectively. Patients with idiopathic intussusception were treated with simple
      reduction, while the others underwent segmental resection because of the
      possibility of malignant tumour. In contrast to intussusception in childhood,
      intussusception in adults usually has a definable lead point and resection of the
      involved bowel, rather than simple reduction, is indicated.

PMID- 17017696
TI  - An unusual case of blunt abdominal trauma: A bleeding and ruptured gall-bladder
      managed by laparoscopy.
AB  - An isolated gall-bladder injury after blunt abdominal trauma is rare.
      Intraluminal bleeding with a perforation and an intra-abdominal haemorrhage is
      even rarer. Early diagnosis is difficult, even with a CT-scan or an US-scan
      available. Clinical suspicion, serial clinical examination and repeated imaging,
      can prevent mortality and morbidity. We present a case where laparoscopy was used
      to diagnose and treat an isolated gall-bladder lesion after blunt abdominal
      trauma.

PMID- 17017695
TI  - Surgery for gastrointestinal endometriosis: indications and results.
AB  - BACKGROUND: Although gastrointestinal endometriosis is an uncommon and often
      unexpected finding, the best treatment requires removal of all endometriotic
      lesions. The purpose of our study was to report our experience with the diagnosis
      and treatment of bowel endometriosis. MATERIAL AND METHODS: From January 1997 to
      January 2004, 13 patients (mean 35.7y ; range 21-55y) were operated for bowel
      endometriosis. We noted: age, history of endometriosis, previous pregnancies,
      preoperative investigations and symptoms, operative procedure and intraoperative
      findings. Follow-up varied between one month postoperative examination and seven
      years. RESULTS: Presenting symptoms of the cases were: acute appendicitis (3),
      dysmenorrhoea (7), constipation (6), pelvic pain (2), rectal bleeding (3) and
      dyspareunia (2). Operative management was performed in accordance with the
      anatomical distribution. Seven patients had a history of previous operations and
      multifocal involvement was present in 61.5% of cases. At a median follow-up of
      12.2 months, 83.3% had complete relief of their initial complaints, with only one
      reoperation needed. The pregnancy rate after surgery was 66.6%. Preoperative
      tests were: ultrasound for ovarian endometriomas, coloscopy, barium enema,
      vaginal palpation for detecting rectovaginal involvement, MRI and CT scan. These
      tests predicted the extension of endometriotic process correctly in 50% of the
      cases. CONCLUSIONS: Endometriosis of the sigmoid and rectum is rare but can give
      rise to severe gastrointestinal and pelvic symptoms. Preoperative investigations
      are not infallible in predicting the extent of the disease, sometimes placing the
      surgeon before a dilemma, because it involves mostly young women in the
      reproductive phase of life. The colorectal surgeon, therefore, should seek the
      advice of an experienced gynaecologist and vice versa. Removal of all
      endometriotic lesions is mandatory for obtaining an optimal relief of symptoms.

PMID- 17017697
TI  - Ruptured femoral pseudo-aneurysm through the skin: a rare vexing complication
      following aortobifemoral reconstruction.
AB  - A man, aged 73, presented with a pulsatile mass in his left groin area after an
      aortobifemoral reconstruction 24 years ago. This case showed a femoral pseudo
      aneurysm that evolved very quickly to rupture through the skin requiring
      emergency operative repair.

PMID- 17017698
TI  - Intra-operative acute leg ischaemia after free fibula flap harvest for mandible
      reconstruction.
AB  - Osteosarcomas of the cranial bones need a large surgical radical resection. The
      best option to reconstruct mandible defect after resection is the free fibula
      flap. In our patient an acute ischaemic leg occurred just after the free fibula
      flap harvest for mandible reconstruction. The abnormal distribution of the calf
      arteries leads to catastrophic consequences. The peroneal artery could be the
      main dominant artery of the leg in a small number of patients. We reported an
      extremely rare case of "peronea magna", described in less than 0.2% of the global
      population. A careful pre-operative workup of the calf vessels is required in all
      the patients who need free fibula flap harvest.

PMID- 17017699
TI  - Massive lower gastro-intestinal bleeding due to small bowel diverticula. A report
      of two cases.
AB  - Gastro-intestinal bleeding from the small bowel is a rare entity. It is difficult
      to determine the source of bleeding because of the unavailability of routine
      small bowel endoscopy. The most common reasons for bleeding from the small bowel
      are tumours, arteriovenous malformations and inflammatory bowel diseases.
      Diverticula of the small bowel are very uncommon. We present two cases of gastro
      intestinal bleeding due to small bowel diverticula. Both of them were diagnosed
      on laparotomy. One had a short segment of small bowel, with six diverticula,
      which was resected. The second case had a long segment of small bowel with
      multiple diverticula. This patient was treated by isolating and excising the
      bleeding diverticulum. Haemodynamically unstable lower gastro-intestinal bleeding
      mandates exploratory laparotomy. Mesenteric angiography and Tc 99 labelled
      erythrocyte scintigraphy can detect the bleeding site. Intra-operative endoscopy
      can be performed safely via an enterotomy and can localize the bleeding site.

PMID- 17017700
TI  - Acute gastro-intestinal obstruction as a late presentation of congenital
      diaphragmatic hernia. A report of three cases.
AB  - Three cases of acute gastro-intestinal obstruction due to incarceration of
      congenital diaphragmatic hernia (Bochdalek hernia) in infants are reported. The
      level of incarceration was stomach, small and large intestine. All of the
      presented posterolateral diaphragmatic defects were small and without a sac.
      History of trauma was absent in all patients. Two girls recovered well while a
      boy died of intracerebral bleeding one month after surgery. Acute gastro
      intestinal obstruction as a late, post neonatal, presentation of congenital
      diaphragmatic hernia is a rare, life-threatening emergency. The combination of
      gastro-intestinal obstruction, circulatory and respiratory distress requires
      urgent gastro-intestinal decompression, fluid resuscitation and ventilatory
      support. Surgery can be performed safely only after pre-operative stabilization.

PMID- 17017701
TI  - Left paraduodenal hernia: a case report.
AB  - Congenital internal hernias often remain unrecognized since they are infrequent
      and produce nonspecific abdominal symptoms. Abdominal imaging during a
      symptomatic episode leads to the diagnosis. Surgical treatment is essential
      regarding the risks of incarceration. We report a case of left paraduodenal
      hernia misdiagnosed for over thirty years despite extensive imaging and surgical
      exploration.

PMID- 17017702
TI  - A left paraduodenal hernia causing acute bowel obstruction: a case report.
AB  - We present the case of a 54-year old woman who presented twice at our emergency
      department with progressive abdominal pain. Over the last few years, multiple
      short periods of abdominal pain had occurred: the pain always resolved
      spontaneously after a few hours. She had no past medical history. CT scan
      revealed a sac-like mass of small bowel loops to the left of the ligament of
      Treitz, consistent with the diagnosis of a left paraduodenal hernia. On
      laparotomy, a left paraduodenal hernia with incarceration of small bowel loops
      was found; the herniated loops were reduced and the hernia orifice closed. The
      anatomy, treatment and importance of considering this uncommon diagnosis when
      examining a patient with acute small bowel obstruction are discussed.

PMID- 17017703
TI  - Gallstone ileus presenting as gastric outlet obstruction (Bouveret's syndrome): a
      case report.
AB  - Gallstone ileus is an uncommon condition that may result when a gallbladder or
      commonduct stone enters into the intestinal tract, usually as a result of an
      internal fistula between the gallbladder and the duodenum. It most frequently
      occurs in the terminal ileum. Gastric outlet obstruction syndrome due to the
      impaction of a gallstone in the duodenum passing through a cholecystoduodenal
      fistula was first reported in 1896 by Bouveret concern in 1-3% of patients with
      gallstone ileus. Since the first case-report, 300 other cases has been documented
      in the literature. Here we report a case of Bouveret's syndrome in order to
      increase awareness of this unusual cause of gastric outlet obstruction.

PMID- 17017704
TI  - Hydatid cyst of the pulmonary artery secondary to hepatic hydatid cyst embolism.
AB  - A cystic lesion of the liver extending into the inferior vena cava was discovered
      in a 33-year old female patient suffering from dyspnea, pain and swelling in the
      legs. Plain chest X-ray was normal. CT and MRI of the thorax showed a cystic
      lesion within the right pulmonary artery. The liver lesion was treated by a
      partial cystectomy and omentoplasty, inferior vena cava and bile ducts repair.
      Through a right thoracotomy, a hydatid cyst was found in the pulmonary artery and
      enucleated. Although very rare, pulmonary artery hydatidosis may be the cause of
      an unexplained dyspnea in patients with hydatidosis of the liver.

PMID- 17017705
TI  - Unusual localization of hydatid cyst.
AB  - We report a case of a single large echinococcal cyst that originated from the
      retroperitoneal space. Diagnosis was confirmed with serologic test and
      radiological examinations. Especially in the endemic areas hydatid cyst should be
      considered when evaluating cystic masses and it can be treated by extraperitoneal
      operation.

PMID- 17017706
TI  - Pyocolpos in an elderly woman.
AB  - BACKGROUND: Pyocolpos, an uncommon accumulation of pus in the vagina, has not
      been previously reported in an elderly woman. CASE: A 76-year-old woman was
      hospitalised with post-menopausal bleeding and fever. Pelvic examination revealed
      an obstructed vagina. A gadolinium MRI showed pyocolpos. After surgical drainage,
      the patient rapidly recovered. CONCLUSION: Pyocolpos in elderly woman may appear
      spontaneously without any history of gynaecologic cancer or trauma.

PMID- 17017707
TI  - Infected abdominal aortic aneurysm treated by in situ replacement with
      cryopreserved arterial homograft.
AB  - Infected abdominal aortic aneurysms are uncommon but not rare (1-3% of all
      abdominal aortic aneurysms). This life-threatening disease can lead to rapid
      uncontrolled sepsis and/or aortic rupture. We report one case that underlines two
      notions. Firstly computed tomography is effective to detect early stages of the
      pathology providing complete depiction of the anatomical abnormalities. Secondly
      infected aortic aneurysm can be successfully treated by antibiotherapy and in
      situ replacement with cryopreserved arterial homograft.

PMID- 17017708
TI  - Modification of the arterial anastomotic technique improves survival in porcine
      single lung transplant model.
AB  - BACKGROUND: Lung transplantation is a valuable therapeutic option for selected
      patients with end-stage pulmonary disease. However, this treatment is complicated
      by ischaemia-reperfusion injury (IRI) of the lung in 10-20% of the recipients. We
      developed an unilateral porcine lung transplant model to study IRI and describe
      our experience with two different arterial anastomotic techniques. MATERIAL &
      METHODS: Twenty four domestic pigs [n = 6 x (donor + recipient)/group] were used
      in this study. Donor lungs were harvested using an antegrade flush with cold
      Perfadex and stored in the same solution for +/- 8 hours. Recipient animals
      underwent a left thoracotomy. After native pneumonectomy, the left donor lung was
      transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3
      pulmonary artery. 2 The outcome in recipients from historical groups differing in
      anastomotic technique was compared. An end-to-end anastomosis on the left
      pulmonary artery was performed in group I versus a patch anastomosis on the main
      pulmonary artery in group II. One hour after reperfusion, the right pulmonary
      artery and main bronchus were ligated forcing the recipient to survive on the
      transplanted lung only. The animals were further observed for 6 hours. RESULTS:
      Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I
      versus 83% (5/6) in group II. Animals in group I died of right heart failure
      manifested by acute dilation of the right ventricle following ligation of the
      hilum of the right lung. CONCLUSION: Single lung transplantation with exclusion
      of the contralateral native lung is a critical model. Arterial end-to-end
      anastomosis resulted in an increased right ventricular afterload. The use of a
      patch technique improved the compliance of the arterial anastomosis and decreased
      early mortality. This transplant model is currently used in our laboratory to
      assess new methods for pulmonary preservation.

PMID- 17017709
TI  - Complex abdominal aortic aneurysm repair.
AB  - ascular surgery is a challenging discipline and complex aneurysms can present an
      entire range of technical difficulties. To overcome these problems good technical
      skills are mandatory. However, it is also worth remembering a few basic rules:
      The simplest solution is often the best. All cases need careful planning,
      including that of the approach. A successful anastomosis requires good aortic
      tissue. Minimal dissection reduces morbidity.

PMID- 17017710
TI  - Management of incidentally found Meckel's diverticulum a new approach: resection
      based on a Risk Score.
AB  - Abstract. The management of incidentally found Meckel's diverticulum (MD) remains
      unclear. The risk for future complications of a non-resected MD must be weighed
      against the risk of complications for a resected MD in order to justify a
      prophylactic resection. Morbidity-rates after resection of incidentally found MD
      are much lower than those after resection of symptomatic MD. Several risk factors
      which increase the risk for future complications of an asymptomatic MD have been
      described in the literature. We suggest that an asymptomatic MD should be removed
      in cases where there is a higher risk of it becoming symptomatic in the future,
      on condition that the resection can be done with presumed low morbidity. Based on
      the literature data we propose a scoring system in order to base the decision for
      surgery on more objective grounds and weighted criteria. This Risk Score is based
      on 4 risk factors: male sex, patients younger than 45 years, diverticula longer
      than 2 cm and the presence of a fibrous band. We suggest resection of an
      asymptomatic MD with a Risk Score of > or = 6 points. A transverse
      diverticulectomy is preferable in most cases. In short, broad based MD, or in the
      case of a palpable mass at the base, a wedge-shaped excision is the best
      alternative.

PMID- 17017711
TI  - The fabulous destiny of surgeons and residents in Belgium: A reflexion on COLLA's
      Law.

PMID- 17017712
TI  - Wouter van Casebancke of Ypres. An unknown medieval surgeon (14th-15th century).

PMID- 17017713
TI  - [Guilt, shame/embarrassment, and empathy].
AB  - This study examined the relationship between empathic responsiveness and the
      proneness to 'zaiakukan' (guilt) and 'shuchishin' (shame and embarrassment). Two
      hundred and thirty five Japanese undergraduates completed a questionnaire of
      Situational Guilt Inventory (Arimitsu, 2002), Situational Shyness Questionnaire
      (Narita, Terasaki, & Niihama, 1990), and Interpersonal Reactivity Index (Davis,
      1983). As predicted, other-oriented empathic responsiveness, which measured
      perspective taking and empathetic concern, had a positive correlation with
      zaiakukan proneness, with shame and embarrassment controlled. On the other hand,
      self-oriented personal distress had a positive correlation with proneness to
      'kihazukashisa', a component of shame and embarrassment, with guilt controlled.
      Inspection of correlations suggested that zaiakukan emerged from other-oriented
      empathy, and shuchishin in men from personal distress, because women's experience
      of shuchishin was less negative than men. Results on private shame were different
      from those in the previous studies (Leith & Baumeister, 1998; Tangney, 1991), and
      were discussed in terms of cultural differences.

PMID- 17017714
TI  - [Examination of eye-movement related factors of representational momentum].
AB  - The judged final position of a moving target that disappears is displaced forward
      (representational momentum: RM), a phenomenon called representational momentum
      (RM). Recently, Kerzel (2000) suggested that RM was elicited by SPEMs after a
      target's offset that moved the persisting image of the target in the direction of
      the motion after the target dissapeared. We examined RM for a target that was not
      pursued by eyes. In Experiment 1 the target and a small dot moved in the same or
      opposite direction. Participants were instructed to pursue the small dot and
      locate the final position of the target. In both conditions the target's motion
      on the retina was expected to be equal to each other. Although the Kerzel's
      hypothesis (2000) predicted negative RM for the target moving in the opposite
      direction of SPEMs, no consistent negative RM was observed. Results of Experiment
      2 suggested that the individual strategy to use the small dot affected RM. Taken
      together, it was shown that Kerzel's lower-level model was not very successful in
      explaining RM, but instead data suggested that predictive mental extrapolation
      and a higher-order individual strategy were involved in the production of RM.

PMID- 17017715
TI  - [The ranking model which estimates the factor scores of residual variables].
AB  - In this research, a new directions for utilizing the residual variable score in
      structural equation modeling was proposed. The residual variable score is created
      by removing the influence of the comprehensive index, which is strongly related
      to brand cognition from each trait factor. By using it as a new index, we tried
      to detect low cognition and high evaluation Brands which are not ranked high in
      the comprehensive index. It was shown that the ranking by the residual variable
      score on the same trait has very high correlation between years and same trait,
      and low correlation with the comprehensive index. Thus, the discriminant validity
      and stability of the new index were identified. Concerning the interpretation of
      the new index, it became clear that the brand which shows an increasing trend
      with the new index has the uniformly low degree of cognition as compared with the
      descending brand. It indicates that the new index has the capability of detecting
      brands with low cognition and high evaluation Brand.

PMID- 17017716
TI  - [The influence of information about drawing technique on impression of paintings:
      in the case of inaccurate perspective].
AB  - Some paintings by renowned artists were drawn in inaccurate perspective, but the
      psychological effects of such technique on impression of paintings were not
      clarified. This study investigated the influence of information about inaccurate
      perspective on impression of paintings. Three famous paintings drawn in
      inaccurate perspective were used as stimuli. In two experiments, participants
      were asked to answer the impression of paintings using two kinds of rating
      scales, information rate scale (IRS) and semantic differential (SD) scale. When
      watching paintings, half of participants were given information about inaccurate
      perspective, and the other half were not. The impressions were compared between
      two groups. Results showed that information about inaccurate perspective
      increased "novelty" impression of paintings that consisted of mainly IRS items.
      We discussed the relationship between perception of inaccurate perspective and
      impression of paintings. Furthermore, we confirmed that it is efficient to
      separate impression of paintings into informational impression measured by IRS
      and semantic impression measured by SD scale in empirical study of paintings.

PMID- 17017717
TI  - [Psychological factors contributing to unsafe behavior in train drivers].
AB  - This research considered whether unsafe behaviors increase the likelihood of
      accident on the railway, and if so, what psychological factors contribute to
      unsafe behaviors? Study 1 investigated how frequently train drivers had committed
      errors and unsafe behaviors when train accidents occurred. Content analysis on
      251 cases of railway accident reports revealed that intention errors (i.e., no
      intention or wrong one) and unsafe behaviors occurred simultaneously in most
      cases of accident. Furthermore, it was suggested that unsafe behaviors contribute
      to the occurrence of accidents. Study 2 examined the effect of psychological
      factors on unsafe behaviors. 148 train drivers completed questionnaires. We
      assumed the causal model that organizational factors affect unsafe behaviors
      indirectly through personal factors. Results of path analysis revealed as
      follows. (a) Concerning personal factors, evaluated cost (e.g., increased
      workload) and ineffectiveness of safety rules increased the frequency of unsafe
      behavior. (b) Concerning organizational factors, organizational management and
      norms increased the frequency of unsafe behavior indirectly through their effects
      on personal factors. Based on these findings, we discussed implications for more
      effective accident prevention.

PMID- 17017718
TI  - [Examination of psychological well-being and subjective well-being in defensive
      pessimists].
AB  - Defensive pessimists (DPs) are considered to be adaptive pessimists because of
      their high performances, but the well-being of DPs have not been sufficiently
      studied. Some studies suggested that DPs have lower well-being than optimists,
      but it is not clear whether their level of well-being is as low as to be
      considered maladaptive. In this study, well-being was distinguished between
      psychological well-being including self-improvement, and subjective well-being as
      in the traditional notion of well-being, and compared well-being among DPs,
      strategic optimists (SOs) and depressed persons (DEPs) in a sample of 303 college
      students (F=160, M=143). Results indicated no significant differences in the
      level of psychological well-being among DPs and SOs, and both of these groups
      scored higher than DEPs. DPs also scored higher than DEPs in subjective well
      being and no differences were found in satisfaction in life between DPs and SOs.
      Thus, this study concluded that the well-being of DPs were high in some regards
      and were not maladaptive.

PMID- 17017719
TI  - [Features of emotional voices: focus in differences between expression and
      recognition].
AB  - This study investigated the relationship between expressed emotions through
      voices and emotions judged from the voices. In Study 1, to prove the judgment of
      emotions in speech, 21 participants evaluated emotions expressed by an actress.
      The average accuracy rate was 67.6%. Some emotions are more likely to be
      interpreted incorrectly than other emotions. The similarities of emotional
      categories caused some misjudgments. In Study 2, verifying the universality of
      judgment, 25 participants judged emotions expressed by 23 speakers. The average
      accuracy rate was 48.6%. Similar to the result of the study 1, there were some
      misjudgments on specific emotions; between sadness and relax, joy and relax, fear
      and sadness, and surprise and anger. To prove the role of acoustic cues, we
      examined the similarities of physical features in emotions using speech-analysis.
      Some emotions have similarities of vocal features and some have similarities of
      emotional categories. In conclusion, this study suggests that the similarities of
      vocal features and emotional categories lead to the judgments of emotions.

PMID- 17017720
TI  - [Does the unintended evaluation for the ambiguous stimulus vary according to the
      context?].
AB  - Research on affective priming effect has studied the process for which the
      positive or negative stimulus is evaluated unintentionally as such, despite the
      fact that many objects in our environment have ambiguous valences. This study
      investigated whether the ambiguous stimulus can be evaluated as positive or as
      negative unintentionally in accordance with the positive or negative consequences
      of the context in which the ambiguous stimulus is presented. One experiment
      (N=30) was conducted to examine whether the positive or negative target word was
      evaluated faster when the consequence of the context in which the preceding
      ambiguous stimulus was presented was consistent with the valence of the target
      word. The consequence of the context was controlled by using easy or difficult
      reward-induced-task for each priming trial. The results showed that the ambiguous
      stimulus was evaluated in accordance with the valence of the context in which the
      stimulus was presented. The process for which the evaluation changes was
      discussed.

PMID- 17017721
TI  - [The asymmetry of interhemispheric interaction in reverse-stroop task].
AB  - The purpose of the present study was to examine the effect of interference on
      interhemispheric interaction in the reverse-stroop task. In two experiments,
      color-word in black ink and color-patch in red or blue ink were briefly presented
      to a bilateral visual-field (BVF). The participants were asked to identify the
      color word, ignoring the color patch. In Experiment 1, color-words written in
      kanji character were used as target ([Chinese character: see test] or [Chinese
      character: see test]). In Experiment 2, color-words written in kana character
      were used as target ([Chinese characters: see test] or [Chinese characters: see
      test]). The result in Experiment I showed that the size of the interference
      effect was invariant irrespective of the visual-field of the target. On the
      contrary, in Experiment 2, the interference effect was larger in the condition
      where the kana color-word was presented to left visual-field (LVF) than to right
      visual-field (RVF). These results suggested that the interference effect would be
      modulated by the dominant hemisphere for processing the target.

PMID- 17017722
TI  - [The influences of narcissism on the justifiability evaluation of anger
      expression].
AB  - In this study, we examined the relationship between the level of narcissism and
      justifiability evaluation of anger expression. Participants, 313 students, were
      asked to rate the justifiability of a variety of anger expressions by them as
      suffering victims, and answer the Narcissistic Personality Inventory-Short
      Version (NPI-S). Results indicated that the higher the sense of superiority and
      competence, which was an aspect of personality, the more justifiable they felt
      their unilateral expression of anger was. In contrast, the higher the need for
      attention and praise, another aspect, the less justifiable they felt their
      unilateral expression was. It was suggested, however, that individuals who had
      higher need for attention and praise tended to appraise suffering situations as
      severer, indicating that they would potentially evaluate anger expression as more
      justifiable. The results suggested that narcissism directly and indirectly
      involved in the justifiability evaluation of anger expression.

PMID- 17017723
TI  - [Effects of structure of self-knowledge on mood-incongruent effect].
AB  - Some people recall more positive memories in negative moods than in neutral
      moods, which is called mood-incongruent effect. Although previous research
      suggested that structure of self-knowledge influences mood-incongruent effect
      (Sakaki, 2004), it is possible that motivation for mood-regulation mediates
      relation between structure of self-knowledge and mood-incongruent effect. The
      present study aimed at exploring this possibility by using self-complexity. In
      Study 1, participants with higher self-complexity, whose self-knowledge has more
      self-aspects with a higher level of differentiation, recalled more positive
      memories in negative moods (compared to neutral moods) than participants with
      lower self-complexity, whose self-knowledge has a fewer self-aspects with larger
      overlap. Study 1 also revealed that these effects hold even when the motivation
      for mood-regulation was partialed out. Study 2 examined mood-incongruent effect
      under positive moods, in which participants are unlikely motivated to alter their
      moods, and it was found that participants with higher self-complexity recalled
      more negative memories in positive moods (compared to neutral moods) than
      participants with lower self-complexity.

PMID- 17017724
TI  - ["The paradox of well-being" and "the crisis" in middle and late adulthood:
      examination from the relationship between aging and self-evaluation].
AB  - The present study focused attention on "the paradox of well-being" and "the
      crisis" of aging discussed in the previous studies, and examined the
      developmental characteristics of middle and late adulthood regarding the
      relationship between subjective experiences of aging and domain-specific self
      evaluation. A questionnaire survey was conducted to 2,026 thirty through 75-year
      old participants. Within a cross-sectional model, "the paradox of well-being" was
      verified. It was suggested that aging is a pivotal component of well-being for
      the middle-aged and elderly. "Leeway and maturation," a positive aspect of
      subjective aging experience, showed positive and far-reaching impacts on self
      evaluation. Its function to limit and minimize the negative effect caused by
      decline was also suggested. The crisis, for men, found in early and post middle
      age, was explained as the accumulation of negative effect of aging, mainly
      relating to the socioeconomic changes. For women, the crisis was inferred to be
      elicited as a negative impact of aging that spilled over to most facets of self
      throughout middle and late adulthood.

PMID- 17017725
TI  - [Intensity of subjective responses in "agari" and cardiovascular and respiratory
      responses].
AB  - The purpose of this study was to investigate the relationship between the
      intensity of subjective responses, called "agari" (stage fright) and
      psychophysiological reactions. We considered "agari" as an internal state of
      psychological and physiological arousal which occurs in performance situations.
      In this study, heart rate (HR), systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and respiration rate (RR) were recorded in the rest period, the
      preparation period, before and after the task, together with some subjective
      measurements. Each of 31 students gave a speech in front of observers
      (experimental condition). They were divided into two groups, the high-arousal
      group (H-group) and low-arousal group (L-group), by the median of "Agari" scores,
      obtained at the preparation period. A different group of 16 students read an
      essay aloud without observers (control group). No differences were found on SBP,
      DBP and RR between H-group and L-group. As for HR, taken in the preparation
      period, H-group and the control group indicated significantly different values,
      but L-group and the control group did not. These results suggest the possibility
      that the intensity of subjective and physiological response of "agari" may be
      discrepant.

PMID- 17017726
TI  - [The measurement of maternal mind-mindedness: its relation to mother-infant
      interaction in natural settings].
AB  - The purpose of this study was to construct an original video-based measurement of
      maternal mind-mindedness (MM). MM is mother's proclivity to treat her infant as
      an individual with mind (Meins, 1997). Participants were 38 mothers and their six
      month-old infants. The results of assessment suggested that there were large
      individual differences not only in frequency of maternal mental attributions, but
      also in the specific contents that mothers read from the filmed infants'
      behaviors. Moreover, it was revealed that these individual differences in MM were
      related to mother-infant interaction styles in natural settings, especially
      maternal comments on infant's internal state and the followings of infant's
      attention. Finally, the usefulness of this measurement in examining the effect of
      MM on the child's development of mind understanding was discussed.

PMID- 17017727
TI  - [Interpersonal intolerance of ambiguity, interpersonal life events, and mental
      health].
AB  - This study examined in the interpersonal context whether interactions of
      intolerance of ambiguity and positive as well as negative life events in a
      diathesis-stress model predicted changes in mental health. College students, 236
      men and women, completed a questionnaire of Revised Interpersonal Intolerance of
      Ambiguity (IIAS-R), Stress Response, and Happiness scales. They completed one and
      a half months later another questionnaire of Interpersonal Life Event, Stress
      Response, and Happiness scales. Hierarchical regression analyses showed that for
      men interaction terms of IIAS-R's Friend scores with a negative life event score
      significantly predicted an increase in stress response. For women, interaction
      terms of IIAS-R's Stranger scores with a negative life event score significantly
      predicted a decrease in happiness. The results suggested that the diathesis
      stress model was partially supported, and men and women were different in terms
      of the criterion mental-health variables that could be predicted by the
      interaction terms.

PMID- 17017728
TI  - [The functional cooperation of the hippocampus and anterior thalamus via the
      fimbria-fornix in spatial memory in rats].
AB  - This study examined whether the cooperation of the hippocampus, and anterior
      thalamus via the fimbria-fornix is involved in the spatial memory. We compared
      the effect of contralateral lesions (Contra) with ipsilateral lesions (Ipsi) of
      the fimbria-fornix and anterior thalamus on the performance of an object
      exploration task and the Morris water maze task. If the hippocampus and anterior
      thalamus take part in a same functional system via fornix, the performance of
      Contra group will be more disruptive than that of Ipsi group. In the object
      exploration task, Contra and Ipsi groups did not differ from Control group in the
      performance of object recognition test. However, the performance of Contra group
      was significantly impaired in the spatial recognition test, compared with two
      other groups. In the Morris water maze task, only Contra group showed deficits in
      spatial learning but not the Ipsi group. These results indicate that
      contralateral, but not ipsilateral lesion caused deficits in spatial memory,
      supporting the notion that the functional cooperation of hippocampus and anterior
      thalamus via fornix is vital for spatial memory.

PMID- 17017729
TI  - [Individual and gender differences in Empathizing and Systemizing: measurement of
      individual differences by the Empathy Quotient (EQ) and the Systemizing Quotient
      (SQ)].
AB  - Empathizing is a drive to identify another person's emotions and thoughts and
      respond to them appropriately. Systemizing is a drive to analyze systems or
      construct systems. The Empathizing-Systemizing (E-S) model suggests that these
      are major dimensions in which individuals differ from each other, and women being
      superior in empathizing and men in systemizing. In this study, we examined new
      questionnaires, the Empathy Quotient (EQ) and the Systemizing Quotient (SQ).
      Participants were 1 250 students, 616 men and 634 women, from eight universities,
      who completed both the EQ and SQ. Results showed that women scored higher than
      men on the EQ, and the result was reversed on the SQ. Results also showed that
      humanities majors scored higher than sciences majors on the EQ, and again the
      result was reversed on the SQ. The results were discussed in relation to the E-S
      theory of gender differences.

PMID- 17017730
TI  - [Cognitive aging mechanism of signaling effects on the memory for procedural
      sentences].
AB  - The aim of this study was to clarify the cognitive aging mechanism of signaling
      effects on the memory for procedural sentences. Participants were 60 younger
      adults (college students) and 60 older adults. Both age groups were assigned into
      two groups; half of each group was presented with procedural sentences with
      signals that highlighted their top-level structure and the other half with
      procedural sentences without them. Both groups were requested to perform the
      sentence arrangement task and the reconstruction task. Each task was composed of
      procedural sentences with or without signals. Results indicated that signaling
      supported changes in strategy utilization during the successive organizational
      processes and that changes in strategy utilization resulting from signaling
      improved the memory for procedural sentences. Moreover, age-related factors
      interfered with these signaling effects. This study clarified the cognitive aging
      mechanism of signaling effects in which signaling supports changes in the
      strategy utilization during organizational processes at encoding and this
      mediation promotes memory for procedural sentences, though disuse of the strategy
      utilization due to aging restrains their memory for procedural sentences.

PMID- 17017731
TI  - In emerging data networks, a role for HIM.

PMID- 17017732
TI  - HIM laboratory: delivering e-HIM technology to colleges and universities-
      virtually.

PMID- 17017733
TI  - In the winds of change, principles provide a steady course.

PMID- 17017734
TI  - Master plan.

PMID- 17017735
TI  - Professional development plans in action.

PMID- 17017736
TI  - Coders wanted, experience required.

PMID- 17017737
TI  - Back to school.

PMID- 17017738
TI  - Work force and education.

PMID- 17017739
TI  - RFID in healthcare.

PMID- 17017740
TI  - Who's on first?

PMID- 17017741
TI  - The new electronic discovery civil rule.

PMID- 17017742
TI  - Job shadowing and the HIPAA privacy rule.

PMID- 17017743
TI  - Skills for an e-HIM environment.

PMID- 17017744
TI  - Kindness as a management tool.

PMID- 17017745
TI  - Therapy coding in long-term care facilities.

PMID- 17017746
TI  - ICD-9-CM coding changes for fiscal year 2007.

PMID- 17017747
TI  - The challenges facing medicine in Delaware.

PMID- 17017748
TI  - Cancer risk assessment and genetics at the Helen F. Graham Cancer Center: model
      for personalized medicine and early intervention.
AB  - This article discusses cancer risk assessment, screening options, referral
      guidelines, and the experience of the Familial Risk Assessment Program at the
      Helen F. Graham Cancer Center. Two clinical situations are described that
      illustrate the impact of genetics in the multidisciplinary approach to managing
      cancer. Identifying risk level in patients will impact mortality in those at high
      risk, as well as psychosocial well-being in those at low risk.

PMID- 17017749
TI  - Groundbreaking Delaware physicians: doctor Robert O. Y. Warren.

PMID- 17017750
TI  - Diabetes--asking the right questions.

PMID- 17017751
TI  - Complementary and alternative medicine use among adults with diabetes in the
      United States.
AB  - OBJECTIVES: Limited population-based data are available on the use of
      complementary and alternative medicine (CAM) among people with diabetes and the
      use of these therapies for disease treatment. This analysis compares the
      prevalence and demographic and health correlates of various CAM therapies among
      people with and without diabetes and documents the use of these therapies for
      treatment for diabetes- and non-diabetes-related conditions. RESEARCH DESIGN AND
      METHODS: Data from the 2002 National Health Interview Survey with a supplemental
      section on CAM use were analyzed. Data on overall use and use of CAM modalities
      in 4 categories were compared by diabetes status and by demographic and health
      characteristics. CAM use for treatment of any health condition, including
      diabetes, was compared by diabetes status. RESULTS: Use of any CAM modality was
      significantly higher for people with diabetes (72.8% vs. 61.2%, P < .01), which
      was largely attributed to their greater use of prayer. Female gender, higher
      education, western US residence, and having at least 2 chronic conditions were
      associated with higher CAM use in both groups. Variations were observed across
      groups in the correlation of CAM use with age, race/ethnicity, and socioeconomic
      status. CAM use for disease treatment was higher among people with diabetes. With
      the exception of diet-based therapies, most CAM use by people with diabetes was
      for non-diabetes conditions. CONCLUSIONS: These data further elucidate the nature
      of CAM use among people with diabetes and stress the need for interaction between
      providers and diabetes patients on CAM use as a self-management modality.

PMID- 17017752
TI  - Randomized trial of a whole-system ayurvedic protocol for type 2 diabetes.
AB  - CONTEXT: Though complementary and alternative medicine (CAM) treatments are
      popular, evidence to support their application to diabetes care is scarce.
      Previous CAM diabetes research has generally focused on single modalities, but
      CAM practitioners more commonly prescribe complex, multimodality interventions.
      OBJECTIVES: The aims of this study were to determine the feasibility and clinical
      impact of a whole-system, Ayurvedic intervention for newly diagnosed people with
      type 2 diabetes. DESIGN: Patients were randomly assigned to either an
      experimental or control arm. SETTING: Group model health maintenance
      organization. PARTICIPANTS: We recruited 60 adult patients with baseline
      glycosylated hemoglobin (HbA1c) values between 6.0 and 8.0. INTERVENTION:
      Treatment for the experimental group included exercise, an Ayurvedic diet,
      meditation instruction, and an Ayurvedic herb supplement (MA 471). Control
      patients attended standard diabetes education classes with primary care clinician
      follow-up. MEASUREMENTS: Clinical outcomes were assessed at 3 and 6 months and
      included HbA1c, fasting glucose, lipids, blood pressure, and weight. RESULTS:
      Ninety-two percent of randomized patients completed the study, and there were no
      significant adverse study-related events. Using analysis of co-variance (ANCOVA),
      we found no significant differences for clinical outcomes at 6 months between on
      study patient groups, though trends favored the Ayurvedic group. When we included
      a factor measuring how much baseline HbA1c exceeded the mean (6.5%), however, we
      found statistically significant improvements in the Ayurvedic group for HbA1c (P
      = .006), fasting glucose (P = .001), total cholesterol (P = .05), low-density
      lipoprotein (LDL) cholesterol (P = .04), and weight (P = .035). CONCLUSIONS:
      These results suggest that the Ayurvedic intervention may benefit patients with
      higher baseline HbA1c values, warranting further research.

PMID- 17017754
TI  - Regenerative effects of pulsed magnetic field on injured peripheral nerves.
AB  - Previous studies confirm that pulsed magnetic field (PMF) accelerates functional
      recovery after a nerve crush lesion. The contention that PMF enhances the
      regeneration is still controversial, however. The influence of a new PMF
      application protocol (trained PMF) on nerve regeneration was studied in a model
      of crush injury of the sciatic nerve of rats. To determine if exposure to PMF
      influences regeneration, we used electrophysiological recordings and
      ultrastructural examinations. After the measurements of conduction velocity, the
      sucrose-gap method was used to record compound action potentials (CAPs) from
      sciatic nerves. PMF treatment during the 38 days following the crush injury
      enhanced the regeneration. Although the axonal ultrastructures were generally
      normal, slight to moderate myelin sheath degeneration was noted at the lesion
      site. PMF application for 38 days accelerated nerve conduction velocity,
      increased CAP amplitude and decreased the time to peak of the CAP. Furthermore,
      corrective effects of PMF on. the abnormal characteristics of sensory nerve
      fibers were determined. Consequently, long-periodic trained-PMF may promote both
      morphological and electrophysiological properties of the injured nerves. In
      addition, corrective effects of PMF on sensory fibers may be considered an
      important finding for neuropathic pain therapy.

PMID- 17017753
TI  - Use of complementary and alternative therapies by rural African Americans with
      type 2 diabetes.
AB  - The prevalence of type 2 diabetes among non-Hispanic African American adults aged
      20 years and older is 11.4%, compared to 8.4% non-Hispanic whites. Given the high
      rate of diabetes in this population, it is important to determine whether African
      Americans use complementary and alternative medicine (CAM), and if so, what kind.
      Such information is important to healthcare professionals who prescribe therapies
      and make self-care recommendations to those with diabetes. The use of CAM by
      African Americans with diabetes has not been well studied, however, particularly
      among those living in rural areas. This descriptive study was conducted in 2
      rural communities in Central Virginia to explore the use of CAM therapies and the
      role of religion and spirituality in dealing with diabetes among adult African
      Americans with type 2 diabetes. Sixty-eight participants attended 1 of 8 focus
      group sessions in various community settings and described their use of
      alternative therapies. According to these sessions, the most common alternative
      therapies used are prayer, diet-based therapies, and natural products. The
      participants' descriptions enhance our understanding of CAM use among rural
      African Americans with diabetes.

PMID- 17017755
TI  - Balance of flora, galt, and mucosal integrity.
AB  - It is clear that there is a dynamic relationship involving the gastrointestinal
      flora, environmental inputs (food and other nutrients), and the health of the
      immune system. Recent research has taught us a great deal about the role of diet
      and commensal bacteria in promoting health. It appears that Nobel Laureate Eli
      Metchnikov may have been correct in his assertion that live bacterial cultures
      are "the elixir of life". We are unlocking a number of secrets about immune
      system functioning, but we keep coming back to a simple intervention that has an
      ever-expanding opus of research to support it, and an extremely low toxicity
      ratio. Future studies will help us to clarify the best strains and the best
      dosages for individual patients and specific conditions. Assessment of commensal
      flora and a genomic scan for markers of immunologic dysregulation will be more
      accurate and more widely available. It appears, however, that the diagnostic and
      therapeutic tools we have to work with today can make a tremendous difference in
      reducing the burden of suffering for our patients. If "form follows function," as
      Buckminster Fuller was fond of saying, then the form of our immune system may be
      following the precise functions that our commensal flora is dictating. We have
      the opportunity to encourage breastfeeding, decrease unnecessary antibiotic and
      antimicrobial usage (especially in the first two years of life), improve oral
      tolerance with a healthy n-6/n-3 fatty acid ratio, and support the development of
      a healthy commensal flora. These actions on behalf of our immune systems will pay
      dividends for years to come.

PMID- 17017757
TI  - Georgia hospitals net big savings on radiology supplies, devices.

PMID- 17017756
TI  - Jeffrey Blumberg, PhD: the nutrition agenda. Interview by Frank Lampe and Suzanne
      Snyder.

PMID- 17017758
TI  - Cardio prices to decline, but inflation looms for others.

PMID- 17017759
TI  - The importance of process in building an executive leadership team: a case study.
AB  - In today's competitive, fast-changing world of healthcare, organizations cannot
      tolerate ineffective leadership over the long term if they are to remain
      successful. It is very common for leadership teams to come together and
      immediately begin to do business...at least to attempt to do what each team
      member believes the group's business should be. Unfortunately, each person
      probably has a different idea of what the team's business should be, and how they
      should go about conducting it. This is a certain recipe for ineffectiveness. The
      following case study examines how the executive team in a health sciences college
      approached the development of an effective leadership team, and discusses the
      importance of process to achieving the desired outcomes. The process so described
      can be used with any leadership team, but it should always be customized to suit
      the unique needs and desires of each team.

PMID- 17017760
TI  - Health policy and the delivery of evidence-based wound care using regional wound
      teams.
AB  - As clinicians practicing wound management in all three sectors of the healthcare
      system, the authors have articulated specific issues relating to wound
      management. There is a lack of awareness of the extent of the problem. Best
      practice guidelines have been developed, however, their adoption and transfer
      into practice have been inconsistent. Basic education in the field is minimal or
      absent across all disciplines. Institutions and agencies lack the infrastructure
      and financial resources to support optimal healthcare delivery in wound
      prevention and management. As a result, there are significant problems and
      inconsistencies in access to wound care across Ontario. This paper reviews the
      issues and background as related to pressure ulcer, diabetic foot ulcer and
      venous leg ulcer. Finally, the authors make specific health policy
      recommendations regarding the implementation of regional wound care teams.

PMID- 17017761
TI  - Regionalization reigns--but is care being delivered accordingly? An evaluation of
      perinatal care delivery in a regionalized child health network.
AB  - The Child Health Network for the Greater Toronto Area (CHN), a network of 20
      hospitals and 9 community care access centres, assessed one component of its
      early progress in building a regionalized system of perinatal care. Focusing on
      the relationship between hospital level of care and gestational age, the study
      showed that most births occurred at appropriately designated facilities. However,
      a quarter of newborns of gestational age <32 weeks were delivered at a lower
      level of care than is considered optimal. CHN's ongoing research will offer
      opportunities to assess the impact of regional models on their foremost goal-
      quality clinical care.

PMID- 17017762
TI  - Waiting time care guarantees: necessity or nemesis?
AB  - One of the priorities of governments in Canada is to reduce long waiting times
      for health services. This has raised the prospect of introducing waiting time
      care guarantees. Such guarantees affirm the healthcare system's social contract
      with the public and provide an entitlement to Canadians to receive timely care.
      There are clinical, legal and political implications, which must be considered
      and well managed before introduction. Other countries have ventured down this
      path. They teach us that waiting time care guarantees are good policy and make
      good sense. Correspondingly, they remind us not to make a promise we are not
      ready to keep.

PMID- 17017763
TI  - What motivates managers to coordinate the learning experience of
      interprofessional student teams in service delivery settings?
AB  - This article addresses the realities of providing interdisciplinary student team
      placements (i.e., experiential team learning for students) in healthcare
      settings. Three site coordinators from different clinical settings in Alberta (a
      geriatric assessment unit, a geriatric dementia care unit, and a primary
      healthcare centre), who facilitated Student Team Placements from the University
      of Alberta (UofA) in 2004, comment on their experiences and incentives for
      participating in interdisciplinary teamwork with students. The coordinators
      suggest that students provide input into the sites' continuous quality
      improvement cycle, contribute to host organizations, and confer benefits for the
      student preceptors, the staff and the patients who participate. The site
      coordinators also recognize and accept the responsibility common to all service
      providers, to model a unique site culture that promotes learning/teaching of team
      skills for health science students. The experience of others in the literature
      supports our findings that two systems--the system to educate health
      professionals and the system that influences the health of the community--can
      interact so that each realizes a mutual benefit.

PMID- 17017764
TI  - Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and
      Mammalian cells.
AB  - Resveratrol is a naturally occurring defense compound produced by a limited
      number of plants in response to stresses. Besides cardiovascular benefits, this
      health-promoting compound has been reported to extend life spans in yeasts,
      flies, worms, and fish. To biosynthesize resveratrol de novo, tyrosine ammonia
      lyase (TAL), 4-coumarate CoA-ligase (4CL), and stilbene synthase (STS) were
      isolated from Rhodobacter sphaeroides, Arabidopsis thaliana, and Vitis vinifera,
      respectively. Yeast cells expressing 4CL and STS produce resveratrol when fed
      with 4-coumaric acid, the substrate of 4CL. When a translational fusion protein
      joining 4CL and STS was used, yeast cells produced 15-fold more resveratrol than
      the cotransformed cells, suggesting that physical localization of 4CL and STS
      facilitate resveratrol production. When the resveratrol pathway was introduced
      into human HEK293 cells, de novo biosynthesis was detected, leading to
      intracellular accumulation of resveratrol. We successfully engineered an entire
      plant natural product pathway into a mammalian host.

PMID- 17017765
TI  - On the mechanism of lead chalcogenide nanocrystal formation.
AB  - On the basis of evidence from 31P NMR spectroscopy, and using PbSe as a model, we
      propose two simultaneous mechanisms through which "monomers" are formed in
      preparations of lead chalcogenide nanocrystals (NCs). In one mechanism, selenium
      is delivered as a Se2- species, whereas in the other, Se0 reacts with metal
      already reduced by the organophosphine. This latter mechanism helps explain the
      sensitivity of NC preparations to the purity of organophosphines and allows the
      rational modification of batch NC reactions to increase yield.

PMID- 17017766
TI  - The catalytic power of uracil DNA glycosylase in the opening of thymine base
      pairs.
AB  - Uracil DNA glycosylase (UNG) locates uracil and its structural congener thymine
      in the context of duplex DNA using a base flipping mechanism. NMR imino proton
      exchange measurements were performed on free and UNG-bound DNA duplexes in which
      a single thymine (T) was paired with a series of adenine analogues (X) capable of
      forming one, two, or three hydrogen bonds. The base pair opening equilibrium for
      the free DNA increased 55-fold as the number of hydrogen bonds decreased, but the
      opening rate constants were nearly the same in the absence and presence of UNG.
      In contrast, UNG was found to slow the base pair closing rate constants (kcl)
      compared to each free duplex by a factor of 3- to 23-fold. These findings
      indicate that regardless of the inherent thermodynamic stability of the TX pair,
      UNG does not alter the spontaneous opening rate. Instead, the enzyme holds the
      spontaneously expelled thymine (or uracil) in a transient extrahelical sieving
      site where it may partition forward into the enzyme active site (uracil) or back
      into the DNA base stack (thymine).

PMID- 17017768
TI  - Electrostatically controlled hierarchical arrangement of monocationic silver(I)
      and dicationic mercury(II) ions between disk-shaped template ligands.
AB  - This paper describes hierarchical arrangement of three Ag+ and three Hg2+ ions
      using two disk-shaped hexa-monodentate template ligands in which three oxazolyl
      rings are arranged each on the two concentric circles. The hierarchical manner of
      ligand arrangement allows the selective binding of monocationic Ag+ and
      dicationic Hg2+ ions to the inner first and the outer second generation
      coordination sites, respectively. This hierarchically well-balanced metal
      assembly should arise primarily from a minimized electrostatic repulsion between
      positively charged six metal ions arranged within the heteronuclear complex.

PMID- 17017767
TI  - Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical
      function to PtlI, a cytochrome P450 of Streptomyces avermitilis.
AB  - A gene cluster encoding all of the enzymes for the biosynthesis of the antibiotic
      pentalenolactone (1) has recently been identified in Streptomyces avermitilis.
      The biosynthetic gene cluster contains the ptlI (SAV2999) gene which encodes a
      cytochrome P450 (CYP183A1). PtlI was cloned by PCR and expressed in Escherichia
      coli as a C-terminal His6-tag protein. Recombinant PtlI bound pentalenene (3)
      with high affinity (KD = 1.44 +/- 0.14 muM). Incubation of recombinant PtlI with
      (+/-)-3 in the presence of NADPH, E. coli flavodoxin and flavodoxin reductase,
      and O2 resulted in conversion to a single enantiomer of pentalen-13-al (7), by
      stepwise allylic oxidation via pentalen-13-ol (6). The steady-state kinetic
      parameters for the oxidation of pentalenene (3) to pentalen-13-ol (6) were kcat =
      0.503 +/- 0.006 min-1 and Km = 3.33+/-0.62 muM for 3.

PMID- 17017769
TI  - A simple technique to grow polymer brushes using in situ surface ligation of an
      organometallic initiator.
AB  - A simple approach is described here for the in-place synthesis of polymer brushes
      by surface-initiated polymerization. A cyano-terminated self-assembled monolayer
      on a gold surface was used to anchor a highly active cationic Pd organometallic
      initiator by ligand exchange. We grew ultrasmooth patterned poly(4
      methoxystyrene) brushes with excellent thickness control at room temperature.

PMID- 17017770
TI  - Patterning of robust self-assembled n-type hexaazatrinaphthylene-based nanorods
      and nanowires by microcontact printing.
AB  - The one-dimensional (1-D) self-assembly property of an n-type
      hexaazatrinaphthylene (HATNA) discotic pi-conjugated molecule was studied.
      Structurally robust unimolecular columnar stacks of HATNA with tunable length
      have been fabricated through a combination of supramolecular self-assembly and
      post-polymerization approach. Moreover, microcontact printing can be utilized to
      transfer the self-assembled nanostructures to the surface to create desired
      functional patterns.

PMID- 17017771
TI  - Stabilization of NH tautomers of quinolines by osmium and ruthenium.
AB  - Complexes OsH2Cl2(PiPr3)2 and RuH2Cl2(PiPr3)2 promote the tautomerization of
      quinoline and 8-methylquinoline to NH tautomers, which lie about 44 kcal.mol-1
      above the usual CH tautomers. The NH tautomers are stabilized by coordination to
      the metal center and by means of a Cl...HN interaction. As a consequence, the six
      coordinate elongated dihydrogen complexes OsCl2{kappa-C2-(HNC9H5R)}(eta2
      H2)(PiPr3)2, the five-coordinate derivatives RuCl2{kappa-C2-(HNC9H5R)}(PiPr3)2,
      and the six-coordinate dihydrogen compounds RuCl2{kappa-C2-(HNC9H5R)}(eta2
      H2)(PiPr3)2 (R = H, Me) have been isolated and characterized.

PMID- 17017772
TI  - Point by point comparison of two thermosensitive polymers exhibiting a similar
      LCST: is the age of poly(NIPAM) over?
AB  - The present Communication compares the thermosensitivity in dilute aqueous
      solutions of well-defined copolymers composed of 95% of 2-(2-methoxyethoxy)ethyl
      methacrylate (MEO2MA) and 5% of oligo(ethylene glycol) methacrylate (OEGMA, Mn =
      475 g.mol-1) and poly(N-isopropylacrylamide) (PNIPAM) samples having similar
      degrees of polymerization and chain-ends. The thermoresponsive behavior of
      P(MEO2MA-co-OEGMA) was found to be overall comparable, and in some cases,
      superior to PNIPAM. Hence, P(MEO2MA-co-OEGMA) copolymers can be considered as
      ideal structures, which combine both the properties of poly(ethylene glycol) and
      PNIPAM in a single macromolecule.

PMID- 17017773
TI  - Proton-induced lewis acidity of unsaturated iridium amides.
AB  - Oxidation of Cp*Ir((rac-TsDPEN)H (DPEN = H2NCHPhCHPhNTs) with Cp2FePF6 or Ph3CPF6
      in MeCN solution generates [Cp*Ir(TsDPEN)(NCMe)]PF6 ([1H(NCMe)]PF6) together with
      H2 and Ph3CH, respectively. Labeling studies revealed that the Ir-H was
      abstracted. The formation of a transient electrophilic species is implicated by
      the formation of a cyclometalated derivative. The labile species [1H(NCMe)]+ was
      also obtained by protonation of the diamido derivative Cp*Ir(TsDPEN-H) (1) in
      MeCN solution (BArF4- = B(C6H3-3,5-(CF3)2)4-). The unsaturated, "naked" cation
      [1H]BArF4 can be prepared by protonation of 1 with H(OEt2)2BArF4 in CH2Cl2
      solution or by thermal elimination of MeCN from [1H(NCMe)]+. Crystallographic
      analysis confirms the structure of this 16e cation in [1H]BArF4. The formally
      unsaturated species 1 and [1H]BArF4 have strongly contrasting Lewis acidities,
      with the cation binding PPh3, CO, and NH3. 1 does not measurably bind these same
      ligands. [1H]BArF4 is reactive toward H2, at least in the absence of inhibiting
      donor ligands such as MeCN. [1H]BArF4 (CH2Cl2 solutions) catalyzes the addition
      of H2 to 1 by proton transfer from an apparent dihydrogen complex. This work
      demonstrates that the protonation activates the Lewis acidity of unsaturated
      Ir(III) amides, giving rise to novel organometallic Lewis acids.

PMID- 17017775
TI  - Chemoselective nucleophilic arylation and single-step oxidative esterification of
      aldehydes using siloxanes and a palladium-phosphinous acid as a reaction switch.
AB  - Aldehydes and siloxanes form methyl esters in a single step through mild
      oxidative esterification in the presence of a palladium catalyst or,
      alternatively, afford secondary alcohols via TBAF-promoted arylation in the
      absence of a catalyst at increased temperatures under otherwise identical
      reaction conditions.

PMID- 17017776
TI  - Facile arene C-H bond activation and alkane dehydrogenation with anionic
      LPt(II)Me2- in hydrocarbon-water systems (L = dimethyldi(2-pyridyl)borate).
AB  - Anionic dimethyldi(2-pyridyl)borato dimethylplatinum(II) complexes react
      vigorously in 3:1 RH/water mixtures to produce PtII aryl (RH = C6H6, para-F2C6H4)
      or hydrido PtII olefin complexes (RH = cyclo-CnH2n; n = 5,6); the Na+ cation
      accelerates the reaction rates dramatically.

PMID- 17017774
TI  - Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using
      stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)
      substituted enzyme.
AB  - In an effort to probe the reaction mechanism of VanX, the d-ala-d-ala dipeptidase
      required for high-level vancomycin resistance in bacteria, stopped-flow kinetic
      and rapid-freeze quench EPR studies were conducted on the Co(II)-substituted
      enzyme when reacted with d-ala-d-ala. The intensity of the Co(II) ligand field
      band at 550 nm decreased (epsilon550 = 140 to 18 M-1 cm-1) when VanX was reacted
      with substrate, suggesting that the coordination number of the metal increases
      from 5 to 6 upon substrate binding. The stopped-flow trace was fitted to a
      kinetic mechanism that suggests the presence of an intermediate whose breakdown
      is rate-limiting. Rapid-freeze quench EPR studies verified the presence of a
      reaction intermediate that exhibits an unusually low hyperfine constant (33 G),
      which suggests a bidentate coordination of the intermediate to the metal center.
      The EPR studies also identified a distinct enzyme product complex. The results
      were used to offer a detailed reaction mechanism for VanX that can be used to
      guide future inhibitor design efforts.

PMID- 17017777
TI  - Soluble molecular compounds with the Mg-O-Al structural motif: a model approach
      for the fixation of organometallics on a MgO surface.
AB  - We report a facile route to the molecular compounds with the Mg-O-Al structural
      motif. The reaction of Mg[N(SiMe3)2]2 (1) with a stoichiometric amount of
      LAlOH(Me) (2) [L = CH{(CMe)(2,6-iPr2C6H3N)}2] in THF/n-hexane at 0 degrees C
      results in the formation of the heterobimetallic compound (Me3Si)2NMg(THF)2-O
      Al(Me)L (3) in high yield. The similar reaction of 1 equiv of Mg[N(SiMe3)2]2 and
      2 equiv of LAlOH(Me) results in the formation of trimetallic compound L(Me)Al-O
      Mg(THF)2-O-Al(Me)L (4). Structural analyses of 3 and 4 have been carried out,
      revealing the presence of the Mg-O-Al motif. A tentative assignment of the Mg-O
      Al vibrations has been made and was supported by calculations.

PMID- 17017778
TI  - 1-Imino nitroxide pyrene for high performance organic field-effect transistors
      with low operating voltage.
AB  - Organic field-effect transistors (OFETs) fabricated with vapor-deposited films of
      1-imino nitroxide pyrene show excellent p-type FET characteristics, with mobility
      up to 0.1 cm2 V-1 s-1 and an on/off ratio of nearly 5 x 104. Most remarkable
      feature of the FETs is their low operating voltage due to the low threshold
      voltage (about -0.6 V) and inverse subthreshold slope (about 540 mV decade-1).

PMID- 17017779
TI  - Iridium(III)-induced isomerization of 2-substituted pyridines to N-heterocyclic
      carbenes.
AB  - Steric strains (F-strain or front-strain) in the acid-base interaction between
      the Lewis acid [TpMe2Ir(C6H5)2] and 2-substituted pyridines Lewis bases, are
      responsible for the stabilization of the C-adducts (2) of the respective pyridine
      carbene tautomers over the expected N-adducts.

PMID- 17017780
TI  - Diastereomerically-specific zirconium complexes of chiral salan ligands:
      isospecific polymerization of 1-hexene and 4-methyl-1-pentene and
      cyclopolymerization of 1,5-hexadiene.
AB  - Chiral Salan ligands were found to wrap in a highly diastereoselective manner
      around zirconium leading to C2-symmetric complexes of predetermined chirality at
      the metal. These complexes led to active polymerization of higher olefins, their
      activity and isospecific induction depending on the nature of the phenolate
      substituents.

PMID- 17017781
TI  - Highly efficient oxidative amidation of aldehydes with amine hydrochloride salts.
AB  - A mild and efficient copper-catalyzed oxidative amidation of aldehydes was
      developed using amine HCl salts and tert-butyl hydroperoxide as an oxidant.

PMID- 17017782
TI  - Stereocontrolled synthesis of beta-D-mannuronic acid esters: synthesis of an
      alginate trisaccharide.
AB  - A facile synthesis route toward beta-linked mannuronic acid oligomers using the
      corresponding 1-thiomannuronic acid esters in combination with the Ph2SO/Tf2O or
      NIS/TMSOTf reagent combinations is presented. The presence of the remotely
      attached carboxylic ester sufficiently influences the electronic environment to
      allow good to excellent beta-selectivities.

PMID- 17017783
TI  - Switching of structural order in a cross-linked polymer triggered by the
      desorption/adsorption of guest molecules.
AB  - A cross-linked polymer, prepared by the in situ polymerization of a thermotropic
      columnar liquid crystal, was found to work as a host with a flexible framework,
      which was reminiscent of intercalation hosts, such as clays, graphites, and
      coordination polymers. The structural order of the cross-linked polymer was
      reversibly switched by changing the amount or shape of a guest incorporated in
      the polymer.

PMID- 17017784
TI  - Chiral Bronsted acid-catalyzed inverse electron-demand aza Diels-Alder reaction.
AB  - Inverse electron-demand aza Diels-Alder reaction of aldimine with enol ethers
      proceeded under the influence of a phosphoric acid diester, derived from (R)
      BINOL, to give tetrahydroquinoline derivatives with excellent enantioselectivity.

PMID- 17017785
TI  - Facile transformation of benzocyclobutenones into 2,3-benzodiazepines via 4pi-8pi
      tandem electrocyclic reactions involving net insertion of diazomethylene
      compounds.
AB  - Efficient transformations of benzocyclobutenones into 2,3-benzodiazepines by a
      formal insertion of diazomethylene compounds are described. This sequential
      process includes nucleophilic addition of diazomethylene anion, oxy-anion
      accelerated o-quinodimethane formation by an electrocyclic ring-opening reaction,
      and 8pi-electrocyclization in one-pot under remarkably mild conditions.
      Intermediary oxy-anion plays an important role for the efficient transformations.

PMID- 17017786
TI  - Catalytic asymmetric reductive amination of aldehydes via dynamic kinetic
      resolution.
AB  - A novel organocatalytic asymmetric reductive amination of aldehydes has been
      developed. Treating racemic alpha-branched aldehydes with p-anisidine and a
      Hantzsch ester in the presence of our previously developed phosphoric acid
      catalyst, TRIP, gave beta-branched secondary amines in excellent yields and
      enantioselectivities via an efficient dynamic kinetic resolution. The process is
      applicable to several different aromatic aldehydes and amines but gives slightly
      reduced enantiomeric ratios with aliphatic aldehydes.

PMID- 17017787
TI  - Kinetic effects of hydrogen bonds on proton-coupled electron transfer from
      phenols.
AB  - The kinetics and mechanism of proton-coupled electron transfer (PCET) from a
      series of phenols to a laser flash generated [Ru(bpy)(3)](3+) oxidant in aqueous
      solution was investigated. The reaction followed a concerted electron-proton
      transfer mechanism (CEP), both for the substituted phenols with an intramolecular
      hydrogen bond to a carboxylate group and for those where the proton was directly
      transferred to water. Without internal hydrogen bonds the concerted mechanism
      gave a characteristic pH-dependent rate for the phenol form that followed a
      Marcus free energy dependence, first reported for an intramolecular PCET in
      Sjodin, M. et al. J. Am. Chem. Soc. 2000, 122, 3932-3962 and now demonstrated
      also for a bimolecular oxidation of unsubstituted phenol. With internal hydrogen
      bonds instead, the rate was no longer pH-dependent, because the proton was
      transferred to the carboxylate base. The results suggest that while a concerted
      reaction has a relatively high reorganization energy (lambda), this may be
      significantly reduced by the hydrogen bonds, allowing for a lower barrier
      reaction path. It is further suggested that this is a general mechanism by which
      proton-coupled electron transfer in radical enzymes and model complexes may be
      promoted by hydrogen bonding. This is different from, and possibly in addition
      to, the generally suggested effect of hydrogen bonds on PCET in enhancing the
      proton vibrational wave function overlap between the reactant and donor states.
      In addition we demonstrate how the mechanism for phenol oxidation changes from a
      stepwise electron transfer-proton transfer with a stronger oxidant to a CEP with
      a weaker oxidant, for the same series of phenols. The hydrogen bonded CEP
      reaction may thus allow for a low energy barrier path that can operate
      efficiently at low driving forces, which is ideal for PCET reactions in
      biological systems.

PMID- 17017788
TI  - Self-assembly of small gold nanoparticles through interligand interaction.
AB  - Stable and monodisperse Au nanoparticles smaller than 2 nm are easily prepared by
      the reduction of HAuCl(4) x 4H(2)O in DMF/H(2)O in the presence of a series of
      bidentate ligands, 2,6-bis(1'-(n-thioalkyl)benzimidazol-2-yl)pyridine (TC(n)BIP,
      n = 3, 6, 8, 10, 12). The TC(n)BIP ligands afford stronger coordination ability
      than alkanethiols due to their bidentate nature. These small nanoparticles form
      hexagonal close-packed (hcp) two-dimensional (2D) superlattices with tunable
      interparticle spacings (from 1.2 to 2.5 nm), produced by changing the length of
      the ligand at both the hydrophobic amorphous carbon and the air-water interface.
      Long-range-ordered hcp 2D superlattices were fabricated through the cleavage and
      construction of interligand pi-pi interactions formed via an annealing process at
      the air-water interface.

PMID- 17017789
TI  - Enantioselective total synthesis of guanacastepene N using an uncommon 7-endo
      Heck cyclization as a pivotal step.
AB  - A convergent, enantioselective total synthesis of (+)-guanacastepene N was
      developed that features a 7-endo Heck cyclization as the key step. In the course
      of this synthesis, short syntheses of the enantiomerically pure cyclopentenone
      and cyclohexene building blocks 5 and 6, which constitute A and C ring fragments
      of guanacastepene N, were developed. These fragments were linked by a challenging
      conjugate addition reaction that also generated the C11 quaternary carbon
      stereocenter. Regioselective 7-endo Heck cyclization gave rise to a tricyclic
      intermediate, which was elaborated to complete the first total synthesis of
      guanacastepene N and the second enantioselective total synthesis of a
      guanacastepene natural product.

PMID- 17017790
TI  - EPR-ENDOR of the Cu(I)NO complex of nitrite reductase.
AB  - With limited reductant and nitrite under anaerobic conditions, copper-containing
      nitrite reductase (NiR) of Rhodobacter sphaeroides yielded endogenous NO and the
      Cu(I)NO derivative of NiR. (14)N- and (15)N-nitrite substrates gave rise to
      characteristic (14)NO and (15)NO EPR hyperfine features indicating NO
      involvement, and enrichment of NiR with (63)Cu isotope caused an EPR line shape
      change showing copper involvement. A markedly similar Cu(I)NONiR complex was made
      by anaerobically adding a little endogenous NO gas to reduced protein and
      immediately freezing. The Cu(I)NONiR signal accounted for 60-90% of the
      integrated EPR intensity formerly associated with the Type 2 catalytic copper.
      Analysis of NO and Cu hyperfine couplings and comparison to couplings of
      inorganic Cu(I)NO model systems indicated approximately 50% spin on the N of NO
      and approximately 17% spin on Cu. ENDOR revealed weak nitrogen hyperfine coupling
      to one or more likely histidine ligands of copper. Although previous
      crystallography of the conservative I289V mutant had shown no structural change
      beyond the 289 position, this mutation, which eliminates the Cdelta1 methyl of
      I289, caused the Cu(I)NONiR EPR spectrum to change and proton ENDOR features to
      be significantly altered. The proton hyperfine coupling that was significantly
      altered was consistent with a dipolar interaction between the Cdelta1 protons of
      I289 and electron spin on the NO, where the NO would be located 3.0-3.7 A from
      these protons. Such a distance positions the NO of Cu(I)NO as an axial ligand to
      Type 2 Cu(I).

PMID- 17017791
TI  - Automated protein structure determination from NMR spectra.
AB  - Fully automated structure determination of proteins in solution (FLYA) yields,
      without human intervention, three-dimensional protein structures starting from a
      set of multidimensional NMR spectra. Integrating existing and new software,
      automated peak picking over all spectra is followed by peak list filtering, the
      generation of an ensemble of initial chemical shift assignments, the
      determination of consensus chemical shift assignments for all (1)H, (13)C, and
      (15)N nuclei, the assignment of NOESY cross-peaks, the generation of distance
      restraints, and the calculation of the three-dimensional structure by torsion
      angle dynamics. The resulting, preliminary structure serves as additional input
      to the second stage of the procedure, in which a new ensemble of chemical shift
      assignments and a refined structure are calculated. The three-dimensional
      structures of three 12-16 kDa proteins computed with the FLYA algorithm coincided
      closely with the conventionally determined structures. Deviations were below 0.95
      A for the backbone atom positions, excluding the flexible chain termini. 96-97%
      of all backbone and side-chain chemical shifts in the structured regions were
      assigned to the correct residues. The purely computational FLYA method is
      suitable for substituting all manual spectra analysis and thus overcomes a main
      efficiency limitation of the NMR method for protein structure determination.

PMID- 17017792
TI  - Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane
      disordering effect by membrane insertion.
AB  - Antimicrobial peptides (AMPs) are a class of peptides that are innate to various
      organisms and function as a defense agent against harmful microorganisms by means
      of membrane disordering. Characteristic chemical and structural properties of
      AMPs allow selective interaction and subsequent disruption of invaders' cell
      membranes. Polymers based on m-phenylene ethynylenes (mPE) were designed and
      synthesized to mimic the amphiphilic, cationic, and rigid structure of AMPs and
      were found to be good mimics of AMPs in terms of their high potency toward
      microbes and low hemolytic activities. Using a Langmuir monolayer insertion
      assay, two mPEs are found to readily insert into anionic model bacterial
      membranes but to differ in the degree of selectivity between bacterial and
      mammalian erythrocyte model membranes. Comparison of grazing incidence X-ray
      diffraction (GIXD) data before and after the insertion of mPE clearly indicates
      that the insertion of mPE disrupts lipid packing, altering the tilt of the lipid
      tail. X-ray reflectivity (XR) measurements of the lipid/mPE system demonstrate
      that mPE molecules insert through the headgroup region and partially into the
      tail group region, thus accounting for the observed disordering of tail packing.
      This study demonstrates that mPEs can mimic AMP's membrane disordering.

PMID- 17017793
TI  - Interplay of structure and reactivity in a most unusual furan Diels-Alder
      reaction.
AB  - Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2
      propenoate reacts rapidly and in high yield with furan and a range of substituted
      furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N
      diethylcarbamoyloxy)-2-propenoate fails to react at all under the same
      conditions. These reactions have been explored using density functional theory
      (DFT) calculations. They reveal a highly polar transition state, which is
      stabilized by the Lewis acid catalyst SnCl(4) and by polar solvents. In the
      presence of both catalyst and solvent, a two-step reaction is predicted,
      corresponding to the stepwise formation of the two new carbon-carbon bonds via
      transition states which have similar energies in all cases. Our experimental
      observations of the lack of reaction of the non-fluorinated dienophile, the
      stereochemical outcomes, and the rate acceleration accompanying furan methylation
      are all well predicted by our calculations. The calculated free energy barriers
      generally correlate well with measured reaction rates, supporting a reaction
      mechanism in which zwitterionic character is developed strongly. An in situ ring
      opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3
      difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the
      formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H
      benzo[1,3]dioxole-3a-carboxylate by a Curtin-Hammett mechanism, has also been
      examined. Substantial steric opposition to Lewis acid binding prevents carbonate
      formation from 2-substituted furans.

PMID- 17017794
TI  - Generation of oxynitrenes and confirmation of their triplet ground states.
AB  - New sulfoximine- and phenanthrene-based photochemical precursors to oxynitrenes
      have been developed. These precursors have been used to examine the chemistry and
      spectroscopy of oxynitrenes. The first EPR spectra of oxynitrenes are reported
      and are consistent with their triplet ground states. Additional support for the
      triplet ground state of oxynitrenes is provided by trapping and reactivity
      studies, nanosecond time-resolved IR investigations, and computational studies.

PMID- 17017795
TI  - Theoretical studies on the bifunctionality of chiral thiourea-based
      organocatalysts: competing routes to C-C bond formation.
AB  - The mechanism of enantioselective Michael addition of acetylacetone to a
      nitroolefin catalyzed by a thiourea-based chiral bifunctional organocatalyst is
      investigated using density functional theory calculations. A systematic
      conformational analysis is presented for the catalyst, and it is shown that both
      substrates coordinate preferentially via bidentate hydrogen bonds. The
      deprotonation of the enol form of acetylacetone by the amine of the catalyst is
      found to occur easily, leading to an ion pair characterized by multiple H-bonds
      involving the thiourea unit as well. Two distinct reaction pathways are explored
      toward the formation of the Michael product that differ in the mode of
      electrophile activation. Both reaction channels are shown to be consistent with
      the notion of noncovalent organocatalysis in that the transition states leading
      to the Michael adduct are stabilized by extensive H-bonded networks. The
      comparison of the obtained energetics for the two pathways allows us to propose
      an alternative mechanistic rationale for asymmetric C-C bond forming reactions
      catalyzed by bifunctional thiourea derivatives. The origin of enantioselectivity
      in the investigated reaction is also discussed.

PMID- 17017796
TI  - Time-resolved in situ studies of oxygen intercalation into SrCoO2.5, performed by
      neutron diffraction and X-ray absorption spectroscopy.
AB  - Electrochemical oxidation of the antiferromagnetically ordered SrCoO(2.5), with
      brownmillerite-type structure, to the cubic ferromagnet SrCoO(3), with perovskite
      structure, has been investigated in situ by neutron diffraction as well as by X
      ray absorption fine structure (XAFS) spectroscopy in specially designed
      electrochemical cells. The neutron diffraction experiments were performed twice,
      using two different wavelengths (lambda = 1.2921(2) and 4.74 A) in order to
      better discriminate structural and magnetic changes as functions of the charge
      transfer. From the neutron diffraction experiments, two intermediate phases,
      SrCoO(2.75) and SrCoO(2.82)(+/-)(0.07), were characterized. No superstructure
      reflections were observed for the corresponding SrCoO(2.75) phase. Instead we
      observed here, for the first time, 3D oxygen ordering during an oxygen
      intercalation reaction, as established for SrCoO(2.82)(+/-)(0.07), which can be
      described as a tetragonal unit cell, related to the perovskite cell by a
      approximately 2(a radical2) and c approximately 2a. The structure of this
      intermediate phase confirms the strongly topotactic character of the oxygen
      intercalation reaction. We were also able to prove, from in situ XAFS
      spectroscopy at the Co absorption edge, that the evolution of the Co valence
      state from formally +3 for SrCoO(2.5) to +4 for the final reaction product
      (SrCoO(3.0)) does not proceed continuously but gives evidence for the formation
      of O(-) species for stoichiometries corresponding to SrCoO(2.82)(+/-)(0.07). The
      use of neutrons (vs X-rays) in the diffraction experiments and the choice of the
      transmission (vs fluorescence) mode in the XAFS experiment guarantee that the
      obtained data well represent bulk and not just surface properties.

PMID- 17017797
TI  - Ligand redox effects in the synthesis, electronic structure, and reactivity of an
      alkyl-alkyl cross-coupling catalyst.
AB  - The ability of the terpyridine ligand to stabilize alkyl complexes of nickel has
      been central in obtaining a fundamental understanding of the key processes
      involved in alkyl-alkyl cross-coupling reactions. Here, mechanistic studies using
      isotopically labeled (TMEDA)NiMe(2) (TMEDA = N,N,N',N'
      tetramethylethylenediamine) have shown that an important catalyst in alkyl-alkyl
      cross-coupling reactions, (tpy')NiMe (2b, tpy' = 4,4',4' '-tri-tert
      butylterpyridine), is not produced via a mechanism that involves the formation of
      methyl radicals. Instead, it is proposed that (terpyridine)NiMe complexes arise
      via a comproportionation reaction between a Ni(II)-dimethyl species and a Ni(0)
      fragment in solution upon addition of a terpyridine ligand to (TMEDA)NiMe(2). EPR
      and DFT studies on the paramagnetic (terpyridine)NiMe (2a) both suggest that the
      unpaired electron resides heavily on the terpyridine ligand and that the proper
      electronic description of this nickel complex is a Ni(II)-methyl cation bound to
      a reduced terpyridine ligand. Thus, an important consequence of these results is
      that alkyl halide reduction by (terpyridine)NiR(alkyl) complexes appears to be
      substantially ligand based. A comprehensive survey investigating the catalytic
      reactivity of related ligand derivatives suggests that electronic factors only
      moderately influence reactivity in the terpyridine-based catalysis and that the
      most dramatic effects arise from steric and solubility factors.

PMID- 17017798
TI  - Cation-pi interaction in the polyolefin cyclization cascade uncovered by
      incorporating unnatural amino acids into the catalytic sites of squalene cyclase.
AB  - It has been assumed that the pi-electrons of aromatic residues in the catalytic
      sites of triterpene cyclases stabilize the cationic intermediates formed during
      the polycyclization cascade of squalene or oxidosqualene, but no definitive
      experimental evidence has been given. To validate this cation-pi interaction,
      natural and unnatural aromatic amino acids were site-specifically incorporated
      into squalene-hopene cyclase (SHC) from Alicyclobacillus acidocaldarius and the
      kinetic data of the mutants were compared with that of the wild-type SHC. The
      catalytic sites of Phe365 and Phe605 were substituted with O-methyltyrosine,
      tyrosine, and tryptophan, which have higher cation-pi binding energies than
      phenylalanine. These replacements actually increased the SHC activity at low
      temperature, but decreased the activity at high temperature, as compared with the
      wild-type SHC. This decreased activity is due to the disorganization of the
      protein architecture caused by the introduction of the amino acids more bulky
      than phenylalanine. Then, mono-, di-, and trifluorophenylalanines were
      incorporated at positions 365 and 605; these amino acids reduce cation-pi binding
      energies but have van der Waals radii similar to that of phenylalanine. The
      activities of the SHC variants with fluorophenylalanines were found to be
      inversely proportional to the number of the fluorine atoms on the aromatic ring
      and clearly correlated with the cation-pi binding energies of the ring moiety. No
      serious structural alteration was observed for these variants even at high
      temperature. These results unambiguously show that the pi-electron density of
      residues 365 and 605 has a crucial role for the efficient polycyclization
      reaction by SHC. This is the first report to demonstrate experimentally the
      involvement of cation-pi interaction in triterpene biosynthesis.

PMID- 17017799
TI  - Giant excitonic Zeeman splittings in colloidal Co2+ -doped ZnSe quantum dots.
AB  - Colloidal Co(2+):ZnSe diluted magnetic semiconductor quantum dots (DMS-QDs) were
      prepared by the hot injection method and studied spectroscopically. Ligand-field
      electronic absorption and magnetic circular dichroism (MCD) spectra confirm
      homogeneous substitutional speciation of Co(2+) in the ZnSe QDs. Absorption
      spectra collected at various times throughout the syntheses reveal that dopants
      are absent from the central cores of the QDs but are incorporated at a constant
      concentration during nanocrystal growth. The undoped cores are associated with
      dopant exclusion from the ZnSe critical nuclei. Analysis of low-temperature
      electronic absorption and MCD spectra revealed excitonic Zeeman splitting
      energies (DeltaE(Zeeman)) of these Co(2+):ZnSe QDs that were substantially
      smaller than anticipated from bulk Co(2+):ZnSe data. This reduction in
      DeltaE(Zeeman) is explained quantitatively by the absence of dopants from the QD
      cores, where dopant-exciton overlap would be greatest. Since dopant exclusion
      from nucleation appears to be a general phenomenon for DMS-QDs grown by direct
      chemical methods, we propose that DeltaE(Zeeman) will always be smaller in
      colloidal DMS-QDs grown by such methods than in the corresponding bulk materials.

PMID- 17017800
TI  - QM/MM study of mechanisms for compound I formation in the catalytic cycle of
      cytochrome P450cam.
AB  - In the catalytic cycle of cytochrome P450cam, after molecular oxygen binds as a
      ligand to the heme iron atom to yield a ferrous dioxygen complex, there are fast
      proton transfers that lead to the formation of the active species, Compound I
      (Cpd I), which are not well understood because they occur so rapidly. In the
      present work, the conversion of the ferric hydroperoxo complex (Cpd 0) to Cpd I
      has been investigated by combined quantum-mechanical/molecular-mechanical (QM/MM)
      calculations. The residues Asp(251) and Glu(366) are considered as proton
      sources. In mechanism I, a proton is transported to the distal oxygen atom of the
      hydroperoxo group via a hydrogen bonding network to form protonated Cpd 0 (prot
      Cpd0: FeOOH(2)), followed by heterolytic O-O bond cleavage that generates Cpd I
      and water. Although a local minimum is found for prot-Cpd0 in the Glu(366)
      channel, it is very high in energy (more than 20 kcal/mol above Cpd 0) and the
      barriers for its decay are only 3-4 kcal/mol (both toward Cpd 0 and Cpd I). In
      mechanism II, an initial O-O bond cleavage followed by a concomitant proton and
      electron transfer yields Cpd I and water. The rate-limiting step in mechanism II
      is O-O cleavage with a barrier of about 13-14 kcal/mol. According to the QM/MM
      calculations, the favored low-energy pathway to Cpd I is provided by mechanism II
      in the Asp(251) channel. Cpd 0 and Cpd I are of similar energies, with a slight
      preference for Cpd I.

PMID- 17017801
TI  - A point mutation converts dihydroneopterin aldolase to a cofactor-independent
      oxygenase.
AB  - Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin
      (1) to 6-hydroxymethyl-7,8-dihydropterin (4) in the folate biosynthetic pathway.
      Substitution of a conserved tyrosine residue at the active site of DHNA by
      phenylalanine converts the enzyme to a cofactor-independent oxygenase, which
      generates mainly 7,8-dihydroxanthopterin (6) rather than 4. 6 is generated via
      the same enol intermediate as in the wild-type enzyme-catalyzed reaction, but
      this species undergoes an oxygenation reaction to form 6. The conserved tyrosine
      residue plays only a minor role in the formation of the enol reaction
      intermediate but a critical role in the protonation of the enol intermediate to
      form 4.

PMID- 17017802
TI  - Observation of highly flexible residues in amyloid fibrils of the HET-s prion.
AB  - We report the observation of undetected (until now) residues of the prion protein
      fragment HET-s(218-289) which give rise to well-resolved (13)C, (15)N, and (1)H
      NMR resonances under high-resolution magic-angle spinning (HRMAS) conditions. The
      observed signals belong to large polymeric units as shown by measuring the
      lateral diffusion constants. The amino acids identified in the spectra are
      compatible with their localization in the segments of the protein which could not
      be detected in earlier solid-state NMR experiments. The observed chemical shifts
      indicate that these residues are in a random-coil conformation. Complementary
      experiments which detect only dynamic or static residues, respectively, strongly
      suggest that they belong to different parts of the same molecule.

PMID- 17017803
TI  - Hydrogen and deuterium exchange on Pt(111) and its poisoning by carbon monoxide
      studied by surface sensitive high-pressure techniques.
AB  - Catalytic hydrogen/deuterium exchange on a platinum (111) single crystal and its
      poisoning with carbon monoxide was studied using scanning tunneling microscopy
      (STM), X-ray photoelectron spectroscopy (XPS), sum frequency generation
      vibrational spectroscopy (SFG), and mass spectrometry under reaction conditions
      at pressures in the mTorr to atmospheric range. At 298 K and in the presence of
      200 mTorr of hydrogen and 20 mTorr of deuterium the surface is catalytically
      active, producing HD with activation energy of approximately 5.3 kcal/mol.
      Addition of 5 mTorr of CO stops the reaction completely. In situ STM images
      reveal an ordered surface structure of chemisorbed CO. At 353 K the addition of 5
      mTorr of CO slows the reaction by 3 orders of magnitude, but HD production
      continues with an activation energy of 17.4 kcal/mol. Changes in coverage and
      adsorption site of CO were followed by XPS and SFG up to a temperature of 480 K.
      From these data, a CO dominated, mobile and catalytically active surface model is
      proposed.

PMID- 17017804
TI  - Rational design of a beta-lactamase inhibitor achieved via stabilization of the
      trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a
      penam sulfone.
AB  - beta-Lactamases are one of the major causes of antibiotic resistance in Gram
      negative bacteria. The continuing evolution of beta-lactamases that are capable
      of hydrolyzing our most potent beta-lactams presents a vexing clinical problem,
      in particular since a number of them are resistant to inhibitors. The efficient
      inhibition of these enzymes is therefore of great clinical importance. Building
      upon our previous structural studies that examined tazobactam trapped as a trans
      enamine intermediate in a deacylation deficient SHV variant, we designed a novel
      penam sulfone derivative that forms a more stable trans-enamine intermediate. We
      report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a
      rationally designed penam sulfone, SA2-13. The compound is covalently bound to
      the active site of wt SHV-1 similar to tazobactam yet forms an additional salt
      bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans
      enamine intermediate. Kinetic measurements show that SA2-13, once reacted with
      SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme
      compared to tazobactam. Stabilizing the trans-enamine intermediate represents a
      novel strategy for the rational design of mechanism-based class A beta-lactamase
      inhibitors.

PMID- 17017805
TI  - Distance-dependent emission from dye-labeled oligonucleotides on striped Au/Ag
      nanowires: effect of secondary structure and hybridization efficiency.
AB  - When fluorescently tagged oligonucleotides are located near metal surfaces, their
      emission intensity is impacted by both electromagnetic effects (i.e., quenching
      and/or enhancement of emission) and the structure of the nucleic acids (e.g.,
      random coil, hairpin, or duplex). We present experiments exploring the effect of
      label position and secondary structure in oligonucleotide probes as a function of
      hybridization buffer, which impacts the percentage of double-stranded probes on
      the surface after exposure to complementary DNA. Nanowires containing
      identifiable patterns of Au and Ag segments were used as the metal substrates in
      this work, which enabled us to directly compare different dye positions in a
      single multiplexed experiment and differences in emission for probes attached to
      the two metals. The observed metal-dye separation dependence for unstructured
      surface-bound oligonucleotides is highly sensitive to hybridization efficiency,
      due to substantial changes in DNA extension from the surface upon hybridization.
      In contrast, fluorophore labeled oligonucleotides designed to form hairpin
      secondary structures analogous to solution-phase molecular beacon probes are
      relatively insensitive to hybridization efficiency, since the folded form is
      quenched and therefore does not appreciably impact the observed distance
      dependence of the response. Differences in fluorescence patterning on Au and Ag
      were noted as a function of not only chromophore identity but also metal-dye
      separation. For example, emission intensity for TAMRA-labeled oligonucleotides
      changed from brighter on Ag for 24-base probes to brighter on Au for 48-base
      probes. We also observed fluorescence enhancement at the ends of nanowires and at
      surface defects where heightened electromagnetic fields affect the fluorescence.

PMID- 17017806
TI  - Total synthesis of (+)-batzelladine A and (-)-batzelladine D via [4 + 2]
      annulation of vinyl carbodiimides with N-alkyl imines.
AB  - A diastereoselective [4 + 2]-annulation of vinyl carbodiimides with chiral N
      alkyl imines has been developed to access the stereochemically rich polycyclic
      guanidine cores of the batzelladine alkaloids. Application of this strategy,
      together with additional key steps such as long-range directed hydrogenation and
      diastereoselective intramolecular iodo-amination, led to highly convergent total
      syntheses of (-)-batzelladine D and (+)-batzelladine A with excellent
      stereocontrol.

PMID- 17017807
TI  - A new concept for the noncovalent binding of a ruthenium-based olefin metathesis
      catalyst to polymeric phases: preparation of a catalyst on Raschig rings.
AB  - A new concept for noncovalent immobilization of a ruthenium olefin metathesis
      catalyst is presented. The 2-isopropoxybenzylidene ligand of a Hoveyda-Grubbs
      carbene is further modified by an additional amino group (7) and immobilization
      is achieved by treatment with sulfonated polystyrene forming the corresponding
      ammonium salt. In this novel strategy for the immobilization of ruthenium-based
      metathesis catalysts, the amino group plays a two-fold role, being first an
      active anchor for immobilization and second, after protonation, activating the
      catalysts (electron donating to electron withdrawing activity switch). The
      polymeric support was prepared by precipitation polymerization which led to small
      bead sizes (0.2-2 microm) and large surface areas. Compared to commercial resins
      this tailor-made phase showed superior properties in immobilization of complex 7.
      This concept of immobilization was applied to glass-polymer composite megaporous
      Raschig rings. Ru catalyst 7 on Raschig rings was used under batch conditions in
      various metathesis reactions, including ring-closing (RCM), cross- (CM) and enyne
      metathesis, to give products of high chemical purity with very low ruthenium
      contamination levels (21-102 ppm). The same ring can be used for up to 6 cycles
      of metathesis.

PMID- 17017808
TI  - The 1/1 and 2/1 approximants in the Sc-Mg-Zn quasicrystal system: triacontahedral
      clusters as fundamental building blocks.
AB  - Single-crystal structures are reported for Sc(3)Mg(0.18(1))Zn(17.73(3)), the 1/1
      approximant crystal (AC), and Sc(11.18(9))Mg(2.5(1))Zn(73.6(2)), the 2/1 AC, in
      the corresponding icosahedral quasicrystal (i-QC) system. The 1/1 AC crystallizes
      in space group Im, a = 13.863(2) A, Z = 8, and the 2/1 AC, in Pa, a = 22.412 (2)
      A, Z = 8. The latter, which is valuable in pointing the way to the QC structure,
      is the best ordered and refined 2/1 example to date. The fundamental building
      blocks in both ACs are triacontahedral clusters centered by smaller multiply
      endohedral Tsai-type arrays; the former are condensed through body-centered-cubic
      packing in the 1/1 and primitive cubic packing in the 2/1 AC. Novel prolate
      rhombohedra centered by Sc-Sc dimers are also generated between triacontahedra in
      the 2/1 AC.

PMID- 17017809
TI  - Designing 129Xe NMR biosensors for matrix metalloproteinase detection.
AB  - Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast
      agents due to the chemical shift sensitivity and large nuclear magnetic signal of
      hyperpolarized (129)Xe. Here, we report the first enzyme-responsive (129)Xe NMR
      biosensor. This compound was synthesized in 13 steps by attaching the consensus
      peptide substrate for matrix metalloproteinase-7 (MMP-7), an enzyme that is
      upregulated in many cancers, to the xenon-binding organic cage, cryptophane-A.
      The final coupling step was achieved on solid support in 80-92% yield via a
      copper (I)-catalyzed [3+2] cycloaddition. In vitro enzymatic cleavage assays were
      monitored by HPLC and fluorescence spectroscopy. The biosensor was determined to
      be an excellent substrate for MMP-7 (K(M) = 43 microM, V(max) = 1.3 x 10(-)(8) M
      s(-1), k(cat)/K(M) = 7,200 M(-1) s(-1)). Enzymatic cleavage of the tryptophan
      containing peptide led to a dramatic decrease in Trp fluorescence, lambda(max) =
      358 nm. Stern-Volmer analysis gave an association constant of 9000 +/- 1,000 M(
      1) at 298 K between the cage and Trp-containing hexapeptide under enzymatic assay
      conditions. Most promisingly, (129)Xe NMR spectroscopy distinguished between the
      intact and cleaved biosensors with a 0.5 ppm difference in chemical shift. This
      difference most likely reflected a change in the electrostatic environment of
      (129)Xe, caused by the cleavage of three positively charged residues from the C
      terminus. This work provides guidelines for the design and application of new
      enzyme-responsive (129)Xe NMR biosensors.

PMID- 17017810
TI  - Modular alpha-helical mimetics with antiviral activity against respiratory
      syncitial virus.
AB  - A 13-residue peptide sequence from a respiratory syncitial virus fusion protein
      was constrained in an alpha-helical conformation by fusing two back-to-back
      cyclic alpha-turn mimetics. The resulting peptide, Ac-(3-->7; 8-->12)-bicyclo
      FP[KDEFD][KSIRD]V-NH(2), was highly alpha-helical in water by CD and NMR
      spectroscopy, correctly positioning crucial binding residues (F488, I491, V493)
      on one face of the helix and side chain-side chain linkers on a noninteracting
      face of the helix. This compound displayed potent activity in both a recombinant
      fusion assay and an RSV antiviral assay (IC(50) = 36 nM) and demonstrates for the
      first time that back-to-back modular alpha-helix mimetics can produce functional
      antagonists of important protein-protein interactions.

PMID- 17017811
TI  - Modular catalysts for diene cycloisomerization: rapid and enantioselective
      variants for bicyclopropane synthesis.
AB  - Deconstructing the tridentate (triphos)Pt(II) first-generation catalysts into
      mixed diphosphine/monophosphine combinations (P(2)P) has led to new, more active
      catalysts for the cycloisomerization of 1,6-, and 1,7-dienes into bicyclo-[3.1.0]
      and -[4.1.0] products. When the diphosphine was the small bite angle dppm,
      reaction rates were approximately 20-fold faster than with triphos, although
      reaction rates and diastereoselectivities were also sensitive to the
      monophosphine (PMe(3) being optimal for rate, PPh(3) being optimal for
      selectivity). When the diphosphine was xyl-BINAP or SEGPHOS, the catalysts were
      enantioselective, and enantio-ratios up to 98:2 were observed. Both sets of
      catalysts showed enhanced functional group tolerance in comparison to the
      original (triphos)Pt(2+) catalyst. X-ray structures for both precatalysts are
      also reported.

PMID- 17017812
TI  - Molecular-level helical stack of a nucleotide-appended oligo(p-phenylenevinylene)
      directed by supramolecular self-assembly with a complementary oligonucleotide as
      a template.
AB  - The nucleotide-appended oligo(p-phenylenevinylene), {bis[2,5-bis(2-methoxyethoxy)
      1,4-phenylene]bis(2,1-ethenediyl-1,4-phenylenemethylene)}bis(2'-deoxy-3'
      thymidylic acid) (8), has been synthesized, and self-assembly of the single
      component 8 and binary self-assembly of 8 with a complementary single-stranded 20
      meric oligodeoxyadenylic acid (9) have been examined in aqueous solutions. Atomic
      force microscopy (AFM), UV-visible (UV-vis), and circular dichroism (CD)
      measurements revealed that right-handed helical stacks with 6.4- and 5.1-nm
      diameters self-assemble from the binary components of 8 and 9 as a template
      depending on the residual stoichiometry of the two components (thymine
      (T):adenine (A) = 1:1 and T:A = 2:1, respectively). The concentration of 9 was
      found to strongly influence the CD spectra of 8 in aqueous solutions.
      Consequently, we concluded that the one side of the thymine moieties in the
      stacked assemblies of 8 complexes with a single chain of 9. Complementary T-A
      base pairs thus formed and induced helical stack of the oligo(p
      phenylenevinylene)s in the binary self-assembly. In contrast, self-assembly of
      the single-component 8 and binary self-assembly of 8 with the noncomplementary 20
      meric oligothymidylic acid (10) produced no remarkable formation of fibrous
      structures like helical stacks.

PMID- 17017813
TI  - Supramolecular nanopatterns self-assembled by adenine-thymine quartets at the
      liquid/solid interface.
AB  - By means of scanning tunneling microscopy (STM), we have observed for the first
      time well-ordered supramolecular nanopatterns formed by mixing two complementary
      DNA bases: adenine (A) and thymine (T), respectively, at the liquid/solid
      interface. By mixing A and T at a specific mixing molar ratio, cyclic structures
      that were distinctly different from the structures observed by the individual
      base molecules separately were formed. From an interplay between the STM findings
      and self-consistent charge density-functional based tight-binding (SCC-DFTB)
      calculation method, we suggest formation of A-T-A-T quartets constructed on the
      basis of A-T base pairing. The formation of the A-T-A-T quartets opens new
      avenues to use DNA base pairing as a way to form nanoscale surface architecture
      and biocompatible patterned surfaces particularly via host-guest complexation
      that might be suitable for drug design, where the target can be trapped inside
      the cavities of the molecular containers.

PMID- 17017817
TI  - Lipid monitoring in patients with schizophrenia prescribed second-generation
      antipsychotics.
AB  - OBJECTIVES: Treatment with second-generation antipsychotic (SGA) medications has
      been linked with increased rates of the metabolic syndrome (i.e., dyslipidemia,
      obesity, and hyperglycemia). Several sets of published recommendations now
      provide clinicians with guidelines for monitoring metabolic parameters in
      individuals with schizophrenia treated with SGAs. However, few data are available
      regarding actual metabolic monitoring practices in this patient population. The
      objectives of the study were to determine baseline lipid monitoring rates for
      individuals with schizophrenia prescribed SGAs during the period prior to the
      publication of monitoring guidelines and to determine whether individuals with
      abnormal lipid levels received follow-up monitoring sooner than individuals with
      normal levels. METHOD: Lipid monitoring rates for 408 individuals with
      schizophrenia who were prescribed SGAs from October 1999 to October 2003 were
      examined using administrative data from a Veterans Affairs facility. Survival
      analysis was used to examine time to follow-up lipid measurement and to compare
      time to follow-up measure for individuals with normal initial lipid levels versus
      those with elevated initial lipid levels. RESULTS: Eighty-five percent of
      individuals had at least 1 measurement for total cholesterol or triglycerides in
      a 4-year period. Abnormal initial measurements predicted significantly earlier
      follow-up monitoring (p < .005 for total cholesterol, p < .05 for triglycerides,
      p < .001 for low-density lipoprotein cholesterol). However, median time to follow
      up measure was 304 days (approximately 10 months) for individuals with elevated
      total cholesterol levels, which is too long for optimal clinical follow-up.
      CONCLUSION: Program managers and clinicians should assess adequacy of monitoring
      and support quality improvement initiatives in this area.

PMID- 17017818
TI  - Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety
      symptoms or disorders: a review.
AB  - OBJECTIVE: The efficacy of antipsychotics in the treatment of primary or comorbid
      anxiety disorders or anxiety symptoms in major depressive disorder or bipolar
      disorder was reviewed. DATA SOURCES: English-language literature cited in MEDLINE
      from January 1, 1968, to December 31, 2005, was searched with the keywords
      anxiety disorder, anxiety symptoms, generalized anxiety disorder, panic disorder,
      obsessive-compulsive disorder, posttraumatic stress disorder, social phobia,
      bipolar disorder, major depressive disorder, Hamilton Rating Scale for Anxiety,
      antipsychotics, typical antipsychotics, atypical antipsychotics, fluphenazine,
      haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine,
      molindone, chlorpromazine, mesoridazine, thioridazine, fluspirilene, penfluridol,
      pipothiazine, flupenthixol, clozapine, olanzapine, risperidone, quetiapine,
      ziprasidone, aripiprazole, amisulpride, and clinical trial. Randomized, double
      blind, placebo-controlled trials and open-label studies with a minimum of 20
      subjects with a DSM-III/IV or ICD-10 diagnosis of anxiety disorder and studies
      without a DSM-III/IV or ICD-10 diagnosis of anxiety disorder but with Hamilton
      Rating Scale for Anxiety (HAM-A) scores as an outcome were prioritized. Studies
      on bipolar disorder or major depressive disorder with the analysis of changes in
      anxiety symptoms were reviewed. Early studies on neurosis/ anxiety or anxious
      depression without a HAM-A component were also reviewed. DATA SYNTHESIS: Six
      trials in primary generalized anxiety disorder (GAD), 15 in refractory obsessive
      compulsive disorder (OCD), 8 in posttraumatic stress disorder (PTSD), 6 in
      neurosis with the HAM-A, 1 in social phobia, and 2 in anxiety symptoms in bipolar
      depression were identified. Low doses of trifluoperazine were superior to placebo
      in the treatment of GAD. Most of the less well-designed studies showed that other
      typical antipsychotics might be superior to placebo or as effective as
      benzodiazepines in the treatment of GAD and other anxiety conditions. In most
      studies, risperidone, olanzapine, and quetiapine augmentation to antidepressants
      was superior to placebo in treating refractory OCD and PTSD. Both olanzapine and
      quetiapine significantly reduced anxiety compared to placebo in studies of
      bipolar depression. CONCLUSION: Except for trifluoperazine, there is no large,
      well-designed study of antipsychotics in the treatment of primary or comorbid
      anxiety symptoms or disorders. The efficacy of these agents in various anxiety
      conditions needs to be further investigated with large, well-designed comparison
      studies.

PMID- 17017819
TI  - Substance use disorder and other predictors of antidepressant-induced mania: a
      retrospective chart review.
AB  - OBJECTIVE: To determine if substance use disorder (SUD) is a predictor of
      antidepressant-induced mania (ADM) in bipolar disorder, correcting for
      confounding factors in a regression model. METHOD: 335 antidepressant trials were
      identified in 98 patients treated in an academic bipolar specialty clinic from
      2000 to 2004. Patient charts were reviewed, and histories of SUD and ADM (primary
      outcome; defined as a hypomanic or manic episode within 12 weeks of beginning an
      antidepressant trial) were identified. Mood disorder diagnoses were made using
      the Structured Clinical Interview for DSM-IV mood module, and SUD diagnoses were
      defined using DSM-IV criteria. Potential confounding variables were also examined
      and included in a multivariable regression model. Concomitant mood stabilizer,
      antimanic, and antidepressant use was adjusted for in the regression model.
      RESULTS: In univariate analyses, there was no evidence of an association between
      ADM and past SUD. However, after adjustment for confounding variables in a
      multivariable regression model, there was a strong relationship (OR = 5.06, 95%
      CI = 1.31 to 19.64, p < .05). Other statistically significant predictors of ADM
      in the regression model were type II subtype of bipolar illness, female gender,
      and tricyclic antidepressant (TCA) use (vs. bupropion). CONCLUSIONS: Along with
      other factors, a history of SUD was a strong predictor of ADM. Possible
      underestimation of ADM in randomized clinical trials may occur due to the
      exclusion of subjects with SUD. Type II illness, female gender, and TCA use also
      appeared to be predictors of ADM, while bupropion use appeared to predict lower
      likelihood of ADM.

PMID- 17017820
TI  - Lifetime trauma exposure in veterans with military-related posttraumatic stress
      disorder: association with current symptomatology.
AB  - OBJECTIVE: This study examined whether trauma exposure before, during, and/or
      after military service contributed to current levels of post-traumatic stress
      disorder (PTSD) and adjustment. Further, we investigated whether trauma exposure
      before military service was mediated or moderated by military trauma in its
      effects on current PTSD and adjustment. METHOD: In this retrospective study,
      archival data from the medical records of 422 male veterans diagnosed with PTSD
      between December 2001 and July 2004 at a Veterans Administration Medical Center
      PTSD clinic were analyzed. Measures included the Clinician-Administered PTSD
      Scale interview as well as self-report measures assessing trauma history, health
      problems, and general psychopathology (including PTSD). RESULTS: Findings
      indicated that nonmilitary-related trauma was prevalent in this sample (90%).
      Regression analyses for PTSD symptom severity revealed that age, greater combat
      exposure, and a history of physical assault after military service were
      significantly associated with more severe PTSD symptoms. Childhood physical
      abuse, adult sexual trauma, and a history of being physically assaulted during
      military service were also significantly associated with PTSD symptom severity.
      Mediational analyses indicated that childhood trauma was associated with both
      adult trauma and increased symptomatology on various outcome measures.
      Moderational analyses indicated that adult trauma exposure moderated the effect
      of childhood trauma exposure on health complaints. CONCLUSIONS: Results suggest
      that several variables, including age, greater combat exposure, and premilitary
      and postmilitary traumas, are associated with increased PTSD symptomatology. This
      finding underscores the importance of conducting a thorough assessment of trauma
      when diagnosing PTSD.

PMID- 17017821
TI  - Selegiline transdermal system for the treatment of major depressive disorder: an
      8-week, double-blind, placebo-controlled, flexible-dose titration trial.
AB  - OBJECTIVE: This study investigated the efficacy, safety, and tolerability of the
      selegiline transdermal system (STS) administered in a dose range of 6 mg/24 hours
      to 12 mg/24 hours for treating major depressive disorder (MDD). METHOD: Patients
      meeting DSM-IV criteria for MDD (N = 265) were randomly assigned to blinded
      treatment with STS or a matching placebo patch for 8 weeks. Patients failing to
      meet or maintain protocol-defined therapeutic response criteria at predetermined
      time points had their STS (or placebo) dose increased. Assessments were conducted
      at weeks 1, 2, 3, 5, 6, and 8. Patients were not required to follow a tyramine
      restricted diet. The study ran from September 2001 through August 2002. RESULTS:
      Selegiline transdermal system treatment resulted in significantly greater
      improvement (p < or = .05) compared with placebo treatment on the 3 depression
      rating scales: the 28-item Hamilton Rating Scale for Depression (HAM-D28)
      (primary outcome measure), the Montgomery-Asberg Depression Rating Scale, and the
      Inventory for Depressive Symptomatology-Self Rated. The treatment effect measured
      by the HAM-D28 was modest, primarily due to insomnia side effects. The
      antidepressant efficacy of STS was substantiated further by the significantly
      greater improvement in core depression symptoms (HAM-D Bech-6 subscale). The side
      effects of highest incidence were application site reactions and insomnia. There
      were no safety concerns based on routine clinical laboratory and
      electrocardiogram monitoring, and there were no occurrences of hypertensive
      crisis. CONCLUSION: Results of this double-blind, placebo-controlled, dose
      titration trial provide evidence of short-term efficacy, safety, and tolerability
      of STS in the dose range of 6 mg/24 hours to 12 mg/24 hours for treatment of MDD.
      Selegiline transdermal system has an improved margin of safety compared with oral
      monoamine oxidase inhibitors and represents a useful addition to the existing
      array of antidepressants.

PMID- 17017822
TI  - Implementation of the Texas Medication Algorithm Project patient and family
      education program.
AB  - OBJECTIVE: This article describes the implementation and utilization of the
      patient and family education program (PFEP) component of the Texas Medication
      Algorithm Project (TMAP). The extent of participation, types of psychoeducation
      received, and predictors of receiving at least a minimum level of education are
      presented. METHOD: TMAP included medication guidelines, a dedicated clinical
      coordinator, standardized assessments of symptoms and side effects, uniform
      documentation, and a PFEP. The PFEP includes phased, multimodal, disorder
      specific educational materials for patients and families. Participants were adult
      outpatients of 1 of 7 community mental health centers in Texas that were
      implementing the TMAP disease management package. Patients had DSM-IV clinical
      diagnoses of major depressive disorder, with or without psychotic features;
      bipolar I disorder or schizoaffective disorder, bipolar type; or schizophrenia or
      schizoaffective disorder. Assessments were administered by independent research
      coordinators. Study data were collected between March 1998 and March 2000, and
      patients participated for at least 1 year. RESULTS: Of the 487 participants,
      nearly all (95.1%) had at least 1 educational encounter, but only 53.6% of
      participants met criteria for "minimum exposure" to individual education
      interventions. Furthermore, only 31.0% participated in group education, and 42.5%
      had a family member involved in at least 1 encounter. Participants with
      schizophrenia were less involved in the PFEP across multiple indicators of
      utilization. Diagnosis, intensity of symptoms, age, and receipt of public
      assistance were related to the likelihood of exposure to minimum levels of
      individual education. CONCLUSION: Despite adequate resources and infrastructure
      to provide PFEP, utilization was less than anticipated. Although implementation
      guidelines were uniform across diagnoses, participants with schizophrenia
      experienced less exposure to psychoeducation. Recommendations for improving
      program implementation and modification of materials are discussed.

PMID- 17017823
TI  - Association study of the 5-HTTLPR polymorphism and depression in 75-Year-Old
      nondemented subjects from the Vienna Transdanube Aging (VITA) study.
AB  - BACKGROUND: The site of effect for the selective serotonin reuptake inhibitors
      (SSRIs) is the serotonin transporter (5-HTT), which is extensively investigated
      for its involvement in depressive symptoms. The 5-HTT gene exhibits a 5'-promoter
      based length polymorphism (5-HTTLPR) that affects the transcription efficiency
      and activity, known as short (S) and long (L) alleles. We studied the association
      of this polymorphism in old age and depression in the Vienna Transdanube Aging
      (VITA) study, excluding subjects with dementia. METHOD: We used retrospective
      data from the baseline of the VITA study, which is a cohort study of all
      inhabitants of a geographical area aged 75 years (N = 544). Depression was
      diagnosed and classified strictly according to the DSM-IV. To eliminate dementia
      effects, we excluded subjects with a Clinical Dementia Rating higher than or
      equal to 1 and/or a Mini-Mental State Examination score lower than 24. Genotyping
      for the 5-HTTLPR L/S allele was conducted using polymerase chain reaction
      methodology. RESULTS: We found significantly higher SS genotype frequency in all
      subjects with past/ present depression compared to controls (trend test, p =
      .01). The SS genotype frequency was especially high in subjects with onset of
      depression before age 65. No correlations were found between genotypes/S allele
      carriers and actual Hamilton Rating Scale for Depression, Short-Geriatric
      Depression Scale, and anxiety scale scores. CONCLUSIONS: These observations of
      higher frequency of the 5-HTTLPR S allele in subjects with past/present
      depression fit with previous findings and point to the important role of 5-HTT in
      depression.

PMID- 17017824
TI  - Duloxetine in the treatment of major depressive disorder: comparisons of safety
      and efficacy in U.S. Hispanic and majority Caucasian patients.
AB  - OBJECTIVE: To evaluate new pharmacotherapies for the treatment of major
      depressive disorder (MDD) in Hispanic Americans, the largest ethnic minority
      group in the United States. METHOD: Efficacy and safety data were pooled from 7
      double-blind, placebo-controlled clinical trials of duloxetine conducted from
      February 1999 through November 2002. English-speaking patients (aged > or = 18
      years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/ day;
      Hispanic, N = 58; Caucasian, N = 748) or placebo (Hispanic, N = 62; Caucasian, N
      = 594) for up to 9 weeks. Efficacy measures included the 17-item Hamilton Rating
      Scale for Depression (HAM-D-17) total score, HAM-D-17 subscales, the Clinical
      Global Impressions-Severity of Illness scale, the Patient Global Impression of
      Improvement scale, and the Visual Analog Scales for pain. Safety was assessed
      using discontinuation rates, treatment-emergent adverse events, vital signs, and
      laboratory analyses. Three sets of data were analyzed using different pooling
      strategies, including exploratory analyses with 470 subjects (Hispanic, N = 51;
      Caucasian, N = 419) receiving the recommended dose of 60 mg. RESULTS: No evidence
      for a differential effect of duloxetine in Hispanic and Caucasian patients was
      found in efficacy outcomes. Discontinuation rates due to adverse events among
      duloxetine-treated patients were 14.0% for Hispanics and 17.0% for Caucasians,
      compared with 3.2% and 5.7%, respectively, for placebo-treated patients (p =
      .671). The type of adverse events and their individual rate of occurrence did not
      differ significantly between Hispanic and Caucasian patients. Mean changes from
      baseline for pulse, blood pressure, weight, and laboratory analytes were small
      and showed no significant differences between Hispanic and Caucasian patients.
      CONCLUSION: In this analysis of pooled data, no evidence for a differential
      effect of duloxetine in Hispanic and majority Caucasian patients was found in
      efficacy or safety outcomes.

PMID- 17017825
TI  - Prevalence of bone mineral density loss in Korean patients with schizophrenia: a
      cross-sectional study.
AB  - OBJECTIVE: This study investigates bone mineral density (BMD) and the association
      between BMD and hormonal changes in Korean patients with schizophrenia. METHOD:
      This cross-sectional study was conducted from January 2005 to June 2005; 195
      inpatients with schizophrenia (DSM-IV) were screened. Among them, 51 patients
      aged 18 to 45 years who had taken haloperidol monotherapy for at least 2 years
      participated in this study. The control group consisted of normal healthy
      volunteers who were of similar ages (N = 57). Bone mineral density was determined
      by a GE Lunar 4500 scanner. Hormone levels were measured by using commercial
      kits. The Student t test, the Pearson chi2 test, the Wilcoxon rank sum test, and
      logistic regression analysis were used for data analysis. RESULTS: Female
      patients, but not male patients, showed significantly lower BMD than the normal
      controls as seen in all bone regions studied. Among 18 female patients with BMD
      loss, 17 patients showed hyperprolactinemia, and 7 showed combined
      hypoestrogenemia. Prolactin levels were significantly higher in the female
      patients with BMD loss compared to those with normal bone density; however, other
      hormone levels were not different between the 2 groups. There was no significant
      difference in hormonal levels between bone loss and normal bone density groups.
      CONCLUSIONS: Bone mineral density loss in patients with schizophrenia tended to
      differ by gender. Decreased BMD compared to normal controls was seen in female
      patients; however, this was not observed in men.

PMID- 17017826
TI  - The relationship between quality of life and clinical efficacy from a randomized
      trial comparing olanzapine and ziprasidone.
AB  - OBJECTIVE: To examine treatment-specific changes in health-related quality of
      life (QOL) among patients with schizophrenia and to assess the association
      between clinical and QOL improvement. METHOD: This post hoc analysis used the
      findings of a 28-week, randomized, multicenter trial of patients with
      schizophrenia (DSM-IV) treated with olanzapine (10-20 mg/day) or ziprasidone (80
      160 mg/day). Data were collected from August 2001 to December 2002. Efficacy was
      measured using the Positive and Negative Syndrome Scale (PANSS). Quality of life
      was assessed with the generic health self-administered Medical Outcomes Study
      Short-Form 36-Item Health Survey (SF-36) and the disease-specific expert
      administered Heinrichs-Carpenter Quality of Life Scale (QLS). Mixed-effects
      repeated-measures and last-observation-carried-forward approaches were used to
      assess the effects of treatment on QOL and the association of clinical outcomes
      to QOL outcomes. RESULTS: Olanzapine- and ziprasidone-treated patients
      demonstrated similar improvement from baseline to endpoint on the SF-36 and QLS.
      All correlations between changes in PANSS scores and the SF-36 were significant
      (p < .001), ranging from -0.159 to -0.400. All correlations between changes in
      PANSS scores and the QLS were significant (p < .0001), ranging from -0.286 to 
      0.603. The correlations between the 2 QOL measures were generally significant but
      small to moderate in magnitude. CONCLUSIONS: The results of this study indicate
      that, in patients with schizophrenia, olanzapine and ziprasidone treatment are
      associated with significant QOL and clinical improvements. Further, the
      significant correlation between change scores on the PANSS and QOL measures
      suggests that treatment-related clinical improvements are associated with
      improved health-related and disease-specific QOL. CLINICAL TRIALS REGISTRATION:
      ClinicalStudyResults.org identifier 2347.

PMID- 17017827
TI  - Clozapine utilization and outcomes by race in a public mental health system: 1994
      2000.
AB  - OBJECTIVE: This study aimed to assess racial differences in clozapine
      prescribing, dosing, symptom presentation and response, and hospitalization
      status. This study extends previous studies of clozapine by examining patient-
      and treatment-related factors that may help explain or eliminate reasons for
      differential prescribing. METHOD: Clozapine records for 373 white and African
      American patients with schizophrenia or schizoaffective disorder treated between
      March 1, 1994, and December 31, 2000, in inpatient mental health facilities in
      the state of Maryland were examined. Records for this study were derived from 3
      state of Maryland databases: the Clozapine Authorization and Monitoring Program,
      the State of Maryland Antipsychotic Database, and the Health Maintenance
      Information System Database. RESULTS: A total of 10.3% of African Americans
      (150/1458) with schizophrenia received clozapine treatment compared with 15.3% of
      whites (223/1453) (chi2 = 16.74, df = 1, p < .001) during inpatient treatment in
      the public mental health system in Maryland. Clozapine doses were lower in
      African Americans relative to whites (385.3 +/- 200.6 vs. 447.3 +/- 230.3 mg/day)
      (t = -2.66, df = 366, p = .008). At the time of clozapine initiation, whites had
      more activating symptoms as measured by the Brief Psychiatric Rating Scale (BPRS)
      (t = -3.98, df = 301, p < .0001); however, African Americans had significantly
      greater improvements in BPRS total symptoms (F = 4.80, df = 301, p = .03) and in
      anxiety/ depressive symptoms during 1 year of treatment with clozapine (F =
      10.04, df = 303, p = .002). The estimated rate of hospital discharge was not
      significantly different for African Americans compared to whites prescribed
      clozapine (log-rank chi2 = 0.523, df = 1, p = .470); however, African Americans
      were more likely than whites to discontinue clozapine during hospitalization (log
      rank chi2 = 4.19, df = 1, p = .041). CONCLUSION: Our data suggest
      underutilization of clozapine in African American populations. This racial
      disparity in clozapine treatment is of special concern because of the favorable
      outcomes associated with clozapine in treatment-resistant schizophrenia and in
      the specific benefits observed in African American patients. More research is
      needed to determine why disparities with clozapine treatment occur and why
      African Americans may be discontinued from clozapine at a higher rate, despite
      potential indicators of equal or greater effectiveness among African Americans
      compared with whites.

PMID- 17017828
TI  - Realistic expectations and a disease management model for depressed patients with
      persistent symptoms.
AB  - OBJECTIVE: To describe the efficacy of currently available treatments for
      depression in achieving remission and to highlight additional strategies for
      those patients who continue to experience persistent depressive symptoms in spite
      of optimal treatment. DATA SOURCES: The authors reviewed the literature
      (electronic and hand searches) on the efficacy of current pharmacologic and
      psychotherapeutic antidepressant treatments and the utility of a chronic disease
      management model. A search of PubMed was conducted for English-language articles
      published from 1980 to 2005 using the keywords depression treatments, outcome,
      course of illness, and treatment resistant depression. DATA SYNTHESIS: Current
      treatments for depression leave a significant minority (20%-40%) of patients with
      persistent depressive symptoms. A disease management model that may be useful for
      major depressive disorder is described. CONCLUSIONS: The goal of treating
      depression to achieve remission, although ideal, is currently unattainable for
      many patients. The long-term care of patients with persisting depressive symptoms
      may be well served by adding a disease management component to the overall
      treatment strategy. Doing so may help to improve coping, interpersonal
      functioning, and quality of life.

PMID- 17017829
TI  - Metabolic syndrome and depression: a cross-sectional analysis.
AB  - OBJECTIVE: To examine the prevalence of the metabolic syndrome in depressive
      outpatients and to identify its correlates in depression. METHOD: This cross
      sectional analysis was performed on 121 depressive outpatients from January 2002
      through January 2004 who were diagnosed at baseline with the Structured Clinical
      Interview for DSM-III-R. The metabolic syndrome was diagnosed at 6-year follow-up
      according to the modified criteria of the National Cholesterol Education Program.
      The severity of depressive symptoms was assessed at follow-up with the Beck
      Depression Inventory and the Hamilton Rating Scale for Depression, and general
      psychopathology was assessed with the Symptom Checklist-90. RESULTS: At 6-year
      follow-up, the prevalence of metabolic syndrome in the study group of depressive
      outpatients was 36% (N = 44). The syndrome was associated with a current
      diagnosis of major depression and overeating, but not with age or sex.
      CONCLUSION: The metabolic syndrome is highly prevalent among patients with a
      history of depression, especially those with current major depression. This may
      have implications for treatment. Furthermore, attention should be focused on the
      physical health of those suffering from depression.

PMID- 17017830
TI  - What is the threshold for symptomatic response and remission for major depressive
      disorder, panic disorder, social anxiety disorder, and generalized anxiety
      disorder?
AB  - OBJECTIVE: Symptom-free remission is a goal for treatment in depression and
      anxiety disorders, but there is no consensus regarding the threshold for
      determining remission in individual disorders. We sought to determine these
      thresholds by comparing, in a post hoc analysis, scores on the Clinical Global
      Impressions scale (CGI) and disorder-specific symptom severity rating scales from
      all available studies of the treatment of major depressive disorder, panic
      disorder, generalized anxiety disorder, and social anxiety disorder with the same
      medication (escitalopram). We also sought to compare the standardized effect
      sizes of escitalopram for these 4 psychiatric disorders. DATA SOURCES AND STUDY
      SELECTION: Raw data from all randomized, double-blind, placebo-controlled, acute
      treatment studies sponsored by H. Lundbeck A/S (Copenhagen, Denmark) or Forest
      Laboratories, Inc. (New York, N.Y.), published through March 1, 2004, with
      patients treated with escitalopram for DSM-IV major depressive disorder (5
      studies), panic disorder (1 study), generalized anxiety disorder (4 studies), or
      social anxiety disorder (2 studies) were compared with regard to the standardized
      effect sizes of change in CGI score and scores on rating scales that represent
      the "gold standard" for assessment of these disorders (the Montgomery-Asberg
      Depression Rating Scale, the Panic and Agoraphobia Scale, the Hamilton Rating
      Scale for Anxiety, and the Liebowitz Social Anxiety Scale, respectively). DATA
      SYNTHESIS: In all indications, treatment with escitalopram showed differences
      from placebo in treatment effect from 0.32 to 0.59 on the CGI-S and CGI-I and
      standardized effect sizes from 0.32 to 0.50 on the standard rating scales. There
      were no significant differences among the different disorders. Moderate to high
      correlations were found between scores on the CGI and the standard scales. The
      corresponding standard scale scores for CGI-defined "response" and "remission"
      were determined. CONCLUSION: Comparison of scores on the standard scales and
      scores on the CGI suggest that the traditional definition of response (i.e., a
      50% reduction in a standard scale) may be too conservative.

PMID- 17017831
TI  - Characteristics of e-therapy web sites.
AB  - OBJECTIVE: This study examined what a person seeking e-therapy services might
      find on the Internet, and how e-therapy Web sites characterize their services and
      providers. METHOD: Using the search engines Google and Yahoo!, we obtained a list
      of 55 e-therapy Web sites, which we reviewed from May 2005 to September 2005. We
      used the search terms online counseling, online therapy, and e-therapy. We
      reviewed the Web sites' content for data in 7 categories: description of
      services, terminology for providers, providers' qualifications, terminology for
      service users, characteristics of clients, information for individuals in crisis,
      and information about confidentiality and security. RESULTS: There was a wide
      range in the Web sites we accessed. Web sites often contained confusing
      information about the nature of the service offered and did not always specify
      qualifications of providers. Some providers did not appear qualified to provide
      the services the Web sites advertised. Other sites offered Internet-based
      services of legitimate mental health professionals. Most sites referred to users
      as clients rather than patients, and some sites specified criteria that would
      render prospective clients ineligible to receive services (e.g., suicidality).
      Some Web sites excluded individuals with specific diagnoses. Web sites were not
      generally proactive about providing resources for visitors in crisis. Less than
      half of the Web sites disclosed limits to client data security and
      confidentiality. CONCLUSION: Experiences with e-therapy might influence a
      patient's attitude toward traditional psychotherapy. With the wide variety in e
      therapy services that are searchable on the Web, clinicians may want to be more
      aware of what their patients might encounter online.

PMID- 17017833
TI  - Clinical features of depressed children and adolescents with various forms of
      suicidality.
AB  - OBJECTIVE: To examine various forms of suicidality specified in DSM-IV and their
      clinical characteristics in a large sample of children and adolescents with major
      depressive disorder (MDD). METHOD: Subjects included 553 children and adolescents
      (aged 7.0-14.9 years) recruited between April 2000 and December 2004 from 23
      mental health facilities in Hungary. Subjects received standardized clinical
      evaluations and best-estimate consensus DSM-IV diagnoses of MDD. All subjects
      were in a current episode of MDD at their assessment date. RESULTS: Approximately
      68% of the sample had recurrent thoughts of death, 48% had suicidal ideation, 30%
      had suicide plan, and 12% had attempted suicide. Compared with nonsuicidal peers,
      suicidal children and adolescents were more severely depressed, had more
      depressive symptoms, and more likely had comorbid disorders. However, depressed
      children and adolescents with various forms of suicidality were very similar in
      clinical characteristics. Feelings of worthlessness, depressed mood, psychomotor
      agitation, and comorbid separation anxiety and conduct disorders were independent
      correlates of at least 1 form of suicidality. Only feelings of worthlessness was
      related to all 4 suicidal behaviors, after adjustment for other depressive
      symptoms, comorbid disorders, and demographics. CONCLUSION: Clinical
      characteristics differ between nonsuicidal and suicidal children and adolescents
      but are very similar across various forms of suicidality. Feelings of
      worthlessness may play a central role in the development of suicidal behavior.
      Interventions toward the enhancement of self-esteem and amelioration of
      underlying psychopathology may be crucial for the prevention of suicide attempts
      in depressed children and adolescents.

PMID- 17017834
TI  - Possible link between childhood separation anxiety and adulthood personality
      disorder in patients with anxiety disorders in Japan.
AB  - OBJECTIVE: The aim of this study was to examine whether childhood separation
      anxiety symptoms associate with adulthood anxiety disorders or personality
      disorders. METHOD: Separation Anxiety Symptom Inventory (SASI), Structured
      Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), and Global
      Assessment of Functioning (GAF) were administered to 134 outpatients with anxiety
      disorders and SASI was administered to 176 healthy volunteers (controls)
      recruited in Japan from April 1999 through November 2003. RESULTS: SASI scores
      were not correlated with age or sex in controls. In contrast, SASI scores were
      higher in patients with anxiety disorders than in controls, especially in women.
      SASI showed good test-retest reliability (Pearson correlation coefficient = 0.8).
      One hundred thirteen patients (84.3%) had no comorbid anxiety disorder while 21
      (15.7%) had any, and those with comorbid anxiety disorder tended to show higher
      SASI scores (p = .053). In total, 60 (44.8%) of 134 patients had at least 1
      personality disorder, and the most frequent disorders were from cluster C
      (36.6%). The subgroup with comorbid personality disorders showed earlier onset (p
      < .01), higher SASI scores (p < .01), and poorer recovery of global functioning
      (p < .05) than the noncomorbid subgroup. Stepwise multiple regression analysis
      revealed that SASI scores were higher in female (p < .05) and younger (p < .01)
      patients and most strongly correlated with number of comorbid personality
      disorders in adulthood (p < .01). CONCLUSION: These results suggest that there is
      a continuum of anxiety disorders from childhood to adulthood, the severity of
      separation anxiety appears to increase the risk of severe anxious-fearful
      personality disorders in adulthood, and those with severe separation anxiety,
      particularly females, may progress to suffer from comorbid adult anxiety
      disorders.

PMID- 17017835
TI  - Use of treatment algorithms for depression.

PMID- 17017836
TI  - Buprenorphine: reflections of an addictions psychiatrist.

PMID- 17017838
TI  - A crossover study of prolactin changes associated with risperidone and
      olanzapine.

PMID- 17017839
TI  - Recurrent priapism associated with use of aripiprazole.

PMID- 17017840
TI  - Intimate partner violence victimization among adults with severe mental illness:
      results of a cross-sectional study.

PMID- 17017841
TI  - Hypertriglyceridemia associated with direct effects of olanzapine rather than
      with weight gain: a case report.

PMID- 17017842
TI  - Internet assessment of obsessive-compulsive disorder.

PMID- 17017843
TI  - A new method to test the effectiveness of sunscreen ingredients in a novel nano
      surface skin cell mimic.
AB  - Photophysical properties of sunscreens are commonly studied in solvent media,
      which do not mimic the skin, or in complex artificial skin systems, which are
      difficult to handle. In an earlier study, we showed that polystyrene nanosphere
      suspensions mimic the mixed polarity environment of skin cell systems. This paper
      presents a new method to quantify the effectiveness of sunscreens in the
      polystyrene nanosphere environment. This method utilizes the intrinsic UV-B
      fluorescence of polystyrene nanospheres. We studied three UV-B sunscreens by this
      new method and compared their extinction coefficients with observed values in
      solvent. The values follow the trend observed in solvents, but the ratio of their
      extinction coefficient in solvent to the value obtained by this new method is 1.3
      1.8 instead of 1. This difference might be caused by the mixed polarity or the
      microgeometry of the nanosphere system. Regardless of the difference in the
      extinction coefficients, this new system can be used to test hundreds of
      chemicals for their sunscreening potential in a cost-effective way. One marked
      advantage of this new method is its ability to test both hydrophobic and
      hydrophilic sunscreening chemicals in the same environment. This is virtually
      impossible for current solvent-based models, which require different solvents for
      hydrophobic and hydrophilic chemicals. The new method also allows the
      simultaneous evaluation of a host of photophysical properties of sunscreening
      chemicals.

PMID- 17017844
TI  - Energetics of cytosine singlet excited-state decay paths--a difficult case for
      CASSCF and CASPT2.
AB  - Three deactivation paths for singlet excited cytosine are calculated at the
      CASPT2//CASSCF (complete active space second-order perturbation//complete active
      space self-consistent field) level of theory, using extended active spaces that
      allow for a reliable characterization of the paths and their energies. The lowest
      energy path, with a barrier of approximately 0.1 eV, corresponds to torsion of
      the C5-C6 bond, and the decay takes place at a conical intersection analogous to
      the one found for ethylene and its derivatives. There is a further path with a
      low energy barrier of approximately 0.2 eV associated with the (n(N),pi*) state
      which could also be populated with a low energy excitation. The path associated
      with a conical intersection between the ground and (n(O),pi*) states is
      significantly higher in energy (> 1 eV). The presence of minima on the potential
      energy surface for the (n,pi*) states that could contribute to the biexponential
      decay found in the gas phase was investigated, but could not be established
      unequivocally.

PMID- 17017845
TI  - Spectral tuning of photoactive yellow protein.
AB  - We report a theoretical study on the optical properties of a small, water-soluble
      photosensory receptor, photoactive yellow protein (PYP). A hierarchical ab initio
      molecular orbital calculation accurately evaluated the optical absorption maximum
      of the wild-type, as well as the lambda(max) values of 12 mutants. Electronic
      excitation of the chromophore directly affects the electronic state of nearby
      atoms in the protein environment. This effect is explicitly considered in the
      present study. Furthermore, the spectral tuning mechanism of PYP was investigated
      at the atomic level. The static disorder of a protein molecule is intimately
      related to the complex nature of its energy landscape. By using molecular
      dynamics simulation and quantum mechanical structure optimization, we obtained
      multiple minimum energy conformations of PYP. The statistical distribution of
      electronic excitation energies of these minima was compared with the hole-burning
      experiment (Masciangioli, T. [2000] Photochem. Photobiol. 72, 639), a direct
      observation of the distribution of excitation energies.

PMID- 17017846
TI  - Reactions with dye free radicals reveal weak redox properties of drugs.
AB  - The calcium release channel (CRC) of the skeletal sarcoplasmic reticulum is rich
      in thiol groups and is strongly regulated by covalent modification of these
      thiols. Oxidizing reagents activate the release channel, whereas reducing
      reagents inhibit the channel. However, most CRC regulators are not thiol
      reagents. Here, we propose that reversible redox interactions are involved in
      regulation of the CRC by nonthiol reagents. This hypothesis was tested with
      several CRC regulators. The local anesthetics tetracaine, procaine and QX-314,
      which block the CRC, behaved as electron donors in reactions with dye free
      radicals. In contrast, ryanodine, caffeine, doxorubicin and daunorubicin,
      compounds known to activate the release channel, all accepted electrons from dye
      anion radicals. Moreover, release of Ca2+ from SR initiated by doxorubicin
      (acceptor) was antagonized by local anesthetics (donors). Based on the redox
      characterization of CRC modulators, we propose a functional model in which
      channel inhibitors and activators act as weak electron donors and acceptors,
      respectively, and shift the thiol-disulfide balance within the release protein.
      The consequence of this model is that, in spite of the chemical diversity of CRC
      modulators, a common mechanism of channel regulation involves the transient
      exchange of electrons between the activator/inhibitor and the CRC.

PMID- 17017847
TI  - The effect of ultraviolet radiation on human viral infections.
AB  - Exposure to UV radiation is recognized to suppress cell-mediated immunity and
      therefore could adversely affect the course of a viral infection. Rodent models
      of viral infection confirm this possibility but the situation in human subjects
      is not so clear, apart from two exceptions. These are herpes simplex, in which
      sunlight exposure can cause reactivation, and certain papillomavirus types in
      which sunlight exposure can lead to the development of nonmelanoma skin cancer.
      In both cases, there are UV response elements in the viral genomes that alter the
      normal interactions between the viruses and the host following exposure, and UV
      induced effects on the immune response occur in addition. These complex
      mechanisms are discussed, and the situation regarding UV radiation and viral
      exanthems plus other viruses, including the retroviruses, summarized. Finally
      viral vaccination is considered in the context of UV exposure and the importance
      of the host's genetic background emphasized. Further research is required to
      evaluate whether sunlight can significantly affect the resistance to common viral
      infections and vaccines.

PMID- 17017848
TI  - A descriptive study comparing health attitudes of urban and rural oncology
      patients.
AB  - INTRODUCTION: Rural patients have poor outcomes in cancer management. Previous
      studies have shown different health beliefs and values in rural populations with
      high levels of stoicism and fatalism, leading to later presentation and
      diagnosis, with subsequent poorer prognosis and survival. This study explores the
      relationship between urban or rural background and health attitudes of newly
      diagnosed oncology patients, attending one oncology unit in north Queensland,
      during a 5 month period. This study is a forerunner to a planned larger project
      to explore the research question: do oncology patients from rural backgrounds
      differ in their health attitudes and hope levels compared with those from urban
      backgrounds? The aim of this study was to determine the utility of the selected
      validated instruments, newly diagnosed patients' willingness and ability to
      complete the composite survey instrument, and to identify likely issues for
      inclusion and/or greater focus in the larger project. As pilot studies are also
      used to develop or refine research questions and hypotheses, this article also
      considers some research questions for the planned large scale study. METHODS:
      Self-administered questionnaire survey of 47 patients newly referred to the
      Medical Oncology Department in The Townsville Cancer Centre. Scales used were:
      the EORTC QLQ-C30 to assess symptom burden and quality of life; the Duke UNS
      Functional Social Support Questionnaire to assess social support; the Herth Hope
      Index to assess hope; and the Multi-Dimensional Health Locus of Control to assess
      health beliefs. Data were collated and transformed according to the various
      scales' scoring manuals. Rurality was ascertained using the RRMA classification
      and patient self-assessment. Uni-variate analyses were conducted as small numbers
      precluded multi-variate analysis. Non-parametric Mann-Whitney U and Kruskal
      Wallis tests were used where data were skewed, or categorical. Monte-Carlo
      estimations of p-values were generated. RESULTS: In all, 28 of 47 patients
      classified as rural, 27 were suitable for curative treatment, and 31 were male.
      Median age was 56 years. Some respondents (17%) identified as 'rural', although
      they had an urban residence, and vice versa. Health attitude scores were not
      affected by global health scores or by intent of treatment (palliative/curative).
      Males scored significantly higher for belief in chance. Rural patients scored
      significantly higher for internal belief and belief in chance. No statistically
      significant differences were evident between rural/urban patients by gender, nor
      social support scores. Hope levels were generally high with no significant
      difference between urban and rural patients, regardless of treatment intent.
      DISCUSSION: The study does reveal differences in health attitudes between urban
      and rural populations; however, there are several confounding factors which may
      contribute to this, especially gender. In this study women were under
      represented. People with fatalistic beliefs (high belief in chance) tend to have
      poor initiative in health matters which may cause delay in seeking treatment, or
      poor compliance with treatment. Analysis is limited by small numbers of patients.
      This study is a pilot to a larger project to investigate health attitudes and
      decisions by oncology patients in northern Queensland. The questionnaire was well
      received by patients, but the need for a dedicated recruitment person was
      evident. There is a need to determine how patients identify in terms of rurality
      over and above their actual place of residence.

PMID- 17017850
TI  - Mechanisms of cancer prevention by green and black tea polyphenols.
AB  - Drinking green tea is associated with decreased frequency of cancer development.
      This review outlines the wide range of mechanisms by which epigallocatechin
      gallate (ECGC) and other green and black tea polyphenols inhibit cancer cell
      survival. EGCG suppressed androgen receptor expression and signalling via several
      growth factor receptors. Cell cycle arrest or apoptosis involved caspase
      activation and altered Bcl-2 family member expression. EGCG inhibited telomerase
      activity and led to telomere fragmentation. While at high concentrations
      polyphenols had pro-oxidative activities, at much lower levels, anti-oxidative
      effects occurred. Nitric oxide production was reduced by EGCG and black tea
      theaflavins by suppressing inducible nitric oxide synthase via blocking nuclear
      translocation of the transcription factor nuclear factor-kappaB as a result of
      decreased IkappaB kinase activity. Polyphenols up- or down-regulated activity of
      a number of key enzymes, including mitogen-activated protein kinases and protein
      kinase C, and increased or decreased protein/mRNA levels, including that of
      cyclins, oncogenes, and tumor suppressor genes. Metastasis was inhibited via
      effects on urokinase and matrix metalloproteinases. Polyphenols reduced
      angiogenesis, in part by decreasing vascular endothelial growth factor production
      and receptor phosphorylation. Recent work demonstrated that EGCG reduced
      dihydrofolate reductase activity, which would affect nucleic acid and protein
      synthesis. It also acted as an aryl hydrocarbon receptor an-tagonist by directly
      binding the receptor's molecular chaperone, heat shock protein 90. In conclusion,
      green and black tea polyphenols act at numerous points regulating cancer cell
      growth, survival, and metastasis, including effects at the DNA, RNA, and protein
      levels.

PMID- 17017851
TI  - Anti-angiogenic cancer therapy based on integrin alphavbeta3 antagonism.
AB  - Angiogenesis, the formation of new blood vessels from pre-existing vasculature,
      is a fundamental process during cancer progression. Anti-angiogenic strategies
      have been pursued for cancer treatment and prevention of cancer recurrence and
      metastasis. Integrins are a family of cell adhesion molecules consisting of two
      non-covalently bound transmembrane subunits (alpha and beta). Much research has
      demonstrated that integrin signaling plays a key role in tumor angiogenesis and
      metastasis. Integrin alphavbeta3 is highly expressed on activated endothelial
      cells and tumor cells but is not present in resting endothelial cells and most
      normal organ systems, which makes it a suitable target for anti-angiogenic cancer
      therapy. In this review we will focus on cancer therapy targeting integrin
      alphavbeta3 while other integrins (such as alpha5beta1, alphaIIbbeta3,
      alphavbeta5, alpha6beta4) will only be briefly mentioned when relevant. MEDI-522
      (a humanized anti-human integrin alphavbeta3 monoclonal antibody) and Cilengitide
      (cyclic peptidic integrin alphavbeta3/alphavbeta5 antagonist) are currently in
      clinical trials for anti-angiogenic cancer therapy. Small interfering RNA (siRNA)
      that specifically silences integrin alphav and/or beta3 was reported to cause
      tumor shrinkage in preclinical xenograft models. Combination of anti-integrin
      alphavbeta3 therapy and other therapeutic approaches (such as chemotherapy,
      radiotherapy and gene therapy) has also been applied for cancer treatment.
      Mounting evidence suggests that there is potentially synergistic effect of
      combined therapeutic approaches over single modality alone. Lastly, integrin
      targeted delivery (drugs, genes, and radioisotopes) and imaging (optical, MRI,
      ultrasound, SPECT, and PET) is discussed in detail.

PMID- 17017852
TI  - Medicinal plants from Peru: a review of plants as potential agents against
      cancer.
AB  - Natural products have played a significant role in drug discovery and development
      especially for agents against cancer and infectious disease. An analysis of new
      and approved drugs for cancer by the United States Food and Drug Administration
      over the period of 1981-2002 showed that 62% of these cancer drugs were of
      natural origin. Natural compounds possess highly diverse and complex molecular
      structures compared to small molecule synthetic drugs and often provide highly
      specific biological activities likely derived from the rigidity and high number
      of chiral centers. Ethnotraditional use of plant-derived natural products has
      been a major source for discovery of potential medicinal agents. A number of
      native Andean and Amazonian medicines of plant origin are used as traditional
      medicine in Peru to treat different diseases. Of particular interest in this mini
      review are three plant materials endemic to Peru with the common names of Cat's
      claw (Uncaria tomentosa), Maca (Lepidium meyenii), and Dragon's blood (Croton
      lechleri) each having been scientifically investigated for a wide range of
      therapeutic uses including as specific anti-cancer agents as originally
      discovered from the long history of traditional usage and anecdotal information
      by local population groups in South America. Against this background, we present
      an evidence-based analysis of the chemistry, biological properties, and anti
      tumor activities for these three plant materials. In addition, this review will
      discuss areas requiring future study and the inherent limitations in their
      experimental use as anti-cancer agents.

PMID- 17017854
TI  - Potential deployment of angiotensin I converting enzyme inhibitors and of
      angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy.
AB  - There is significant evidence that both angiotensin I converting enzyme
      inhibitors (ACEI) and type 1 and type 2 angiotensin 2 (A2) receptor blockers may
      inhibit tumor growth. The finding is supported by many reports where these two
      classes of drugs showed cytostatic effects on the cultures of several lines of
      both normal and neoplastic cells. These drugs often transformed the cellular
      biochemical structures, especially in neoplastic cell lines. The same drugs also
      delayed the growth of different types of tumors in a variety of experimental
      animals (breast and lung carcinoma in mice; sarcomas, squamous cell carcinomas
      and hepatocellular carcinomas in rats), and there are a few reports of successful
      treatment of a limited number of cases of Kaposi sarcoma and gliomas with these
      drugs. Retrospective studies in hypertensive subjects treated with ACEI or A2
      receptor blockers also seem to indicate that the incidence and growth of
      different neoplasms was delayed when these patients were compared to hypertensive
      patients receiving alternate medications. There is strong indication that the
      pharmacologic effect of these drugs may be exerted by reduction or inhibition of
      the synthesis of angiotensin 2. A2 is a powerful mitogen and its effect on
      cellular growth is exerted through stimulation of many factors, including
      transforming growth factor beta (TGFbeta), epidermal growth factor (EGF), smooth
      muscle actin (SMA), and tyrosine kinase. A2 also regulates apoptotic mechanisms
      and angiogenesis. The pharmacologic action of most of these drugs, however, is
      not necessarily limited to downregulaton of A2. Many ACEI, especially those
      containing the sulfhydryl (SH group), possess antioxidant or metalloprotease
      inhibitory properties per se. These experimental and retrospective data justify
      clinical testing of these drugs in appropriate randomized trials. Several such
      trials are currently in process. If these trials confirm the experimental and
      retrospective studies, these agents will provide a significant contribution to
      the therapeutic treatment of many malignancies in humans.

PMID- 17017853
TI  - Targeting the hedgehog signaling pathway with small molecules.
AB  - In addition to the potential stem cells offer for regenerative medicine, they
      also rapidly are becoming a center of focus in oncology. There are several
      developmental pathways that are involved in the deregulated signaling in stem
      cells resulting in tumorigenesis. For example, aberrant activation of the
      Hedgehog (Hh) pathway has been associated with numerous malignancies including
      basal cell carcinoma, medulloblastoma, prostate, pancreatic and breast cancers.
      In vivo evidence suggests the antagonism of excessive Hh signaling may provide a
      route to unique mechanism-based anti-cancer therapies. This review summarizes
      recent developments in targeting cell-surface proteins and intracellular targets
      from the Hh pathway with small molecules. Hh signaling is triggered by lipid
      modified Hh proteins that exert their activity via a series of transmembrane
      receptors (Patched, Ptc and Smoothened, Smo). Smoothened (Smo) is a 7-TM protein
      reported to be the most druggable target in the Hh signaling cascade. We further
      review several published programs geared towards identification and profiling of
      synthetic antagonists of Smo. Challenges and perspectives of this approach are
      also discussed.

PMID- 17017855
TI  - Selected players in the inflammation cascade and drugs that target these
      inflammation genes against metastasis.
AB  - Despite many recent advances the prognosis of cancer patients with metastasis
      still remains poor. In metastatic invasion, tumor cells interact with endothelial
      cells through several distinct adhesion molecules. Adherent tumor cells
      extravasate into tissues by degrading basement membranes with matrix degrading
      enzymes such as heparanases and matrix metalloproteinases. Endothelial expression
      of matrix degrading enzymes and adhesion molecules are under the control of
      inflammatory cytokines. These inflammatory proteins and the signaling pathways
      involved in the expression of these genes are under intense investigation as
      therapeutic targets to prevent tumor growth and metastasis. The current review
      focuses on selected players of the inflammation cascade and drugs that target
      these inflammatory genes.

PMID- 17017856
TI  - Recent improvements in the use of synthetic peptides for a selective photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) is a relatively new cytotoxic treatment, predominantly
      used in anti-cancer approaches, that depends on the retention of photosensitizers
      in tumor and their activation after light exposure. Photosensitizers are
      photoactive compounds such as porphyrins and chlorins that upon photoactivation,
      effect strongly localized oxidative damage within the target cells. The ability
      to confine activation of the photosensitizer by restricting illumination to the
      tumor allows for a certain degree of selectivity. Nevertheless, the targeted
      delivery of photosensitizers to defined cells is a major problem in PDT of
      cancer, and one area of importance is photosensitizer targeting. Alterations or
      increased levels in receptor expression of specific cellular type occur in the
      diseased tissues. Therefore, photosensitizers can be covalently attached to
      molecules such as peptides, leading to a receptor-mediated targeting strategy.
      These active-targeting approaches may be particularly useful for anti-vascular
      PDT. Moreover, it has been shown that the photocytotoxicity of photodynamic drugs
      could be enhanced by delivering high amounts of a photosensitizer into
      subcellular organelles such as the nucleus where nucleic acids represent target
      molecules sensitive to photodamage. The recent progresses in the use of active
      targeting strategy with synthetic peptides and the interest of using an active
      targeting strategy in PDT, which could allow efficient cellular internalization
      of photosensitizers, are described in this review.

PMID- 17017857
TI  - Anti-cancer activities of 1,4-naphthoquinones: a QSAR study.
AB  - Quinone moieties are present in many drugs such as anthracyclines, daunorubicin,
      doxorubicin, mitomycin, mitoxantrones and saintopin, which are used clinically in
      the therapy of solid cancers. The cytotoxic effects of these quinones are mainly
      due to the following two factors: (i) inhibition of DNA topoisomerase-II and,
      (ii) formation of semiquinone radical that can transfer an electron to oxygen to
      produce super oxide, which is catalyzed by flavoenzymes such as NADPH-cytochrome
      P-450 reductase. Both semiquinone and super oxide of quinones can generate the
      hydroxyl radical, which is the cause of DNA strand breaks. 1,4-naphthoquinone
      contains two quinone groups that have the ability to accept one or two electrons
      to form the corresponding radical anion or di-anion species. It is probably
      dependent on the quinone redox cycling that yields "reactive oxygen species"
      (ROS) as well as arylation reactions, which is common to quinones for biological
      relevance. In the present review, an attempt has been made to collect the
      cytotoxicity data on different series of 1,4-naphthoquinones against four
      different cancer cell lines that are L1210, A549, SNU-1, and K562, which were
      acquired by using identical method, and has been discussed in terms of QSAR
      (quantitative structure-activity relationships) to understand the chemical
      biological interactions. QSAR results have shown that the cytotoxic activities of
      1,4-naphthoquinones depend largely on their hydrophobicity.

PMID- 17017859
TI  - Molecular insights into mechanisms of the cell death program: role in the
      progression of neurodegenerative disorders.
AB  - Synaptic degeneration and death of neurons in limbic and cortical brain regions
      are the fundamental processes responsible for the manifestation of cognitive
      dysfunction and behavioural abnormalities in Alzheimer's disease (AD). Despite
      the various genetic and environmental factors, and the aging process itself that
      may lead to the manifestation of AD, multiple evidence from studies in
      experimental models and in AD brain tissue demonstrate that the underlying
      neurodegeneration is associated with morphological and biochemical features of
      apoptosis. At the cellular level, neuronal apoptosis in AD may be initiated by
      oxidative stress and related DNA damage, disruption of cellular calcium
      homeostasis, or endoplasmic reticulum (ER) stress. The molecular mechanisms of
      the biochemical cascades of apoptosis are beginning to be understood and involve
      upstream effectors such as Par-4, p53, and pro-apoptotic Bcl-2 family members,
      which mediate mitochondrial dysfunction and subsequent release of pro-apoptotic
      proteins, such as cytochrome c or apoptosis inducing factor (AIF), and subsequent
      caspase-dependent and -independent pathways which finally result in degradation
      of proteins and nuclear DNA. The regulation of apoptotic cascades is complex and
      involves transcriptional control as well as posttranscriptional protein
      modifications, such as protease-mediated cleavage, ubiquitination or poly(ADP
      ribosylation). More recently, the regulation of protein phosphorylation by
      kinases and phosphatases is emerging as a prerequisite mechanism in the control
      of the apoptotic cell death program. A better understanding of the molecular
      underpinnings of neuronal apoptosis will lead to novel preventive and therapeutic
      approaches to the neurodegenerative processes in Alzheimer's disease and other
      neurological disorders where programmed cell death is prominent.

PMID- 17017860
TI  - A genomic approach to investigate neuronal apoptosis.
AB  - Apoptosis has been postulated to play a possible causal role in the onset of
      Alzheimer's disease due to shortage of trophic supply, deafferentation and
      excessive production of free radicals. Many experiments in the past have
      demonstrated the requirement of de novo gene expression during neuronal
      apoptosis. In view of the possible involvement of apoptotic processes in
      Alzheimer's disease and to begin a comprehensive survey of the gene-based
      molecular mechanisms that underlie these events we have used genome scale
      screening by DNA microarray technology in cerebellar granule neurons following
      serum and potassium deprivation. From the 8740 genes interrogated by the
      microarrays, 423 genes were found regulated both at the transcriptional and post
      transcriptional level and segregated into distinct clusters. Functional
      clustering based on gene ontologies showed coordinated expression of genes with
      common biological functions and metabolic pathways. Among the genes implicated in
      apoptotic cerebellar granule neurons, 70 were in common with those differentially
      expressed in cortical neurons exposed to amyloid beta-protein, indicating the
      existence of common mechanisms responsible of neuronal cell death. This new
      approach offer a genomic view of the changes that accompany neuronal apoptosis
      and yield new insights into the molecular basis underlying it.

PMID- 17017861
TI  - Role of protein conformational dynamics and DNA integrity in relevance to
      neuronal cell death in neurodegeneration.
AB  - Apoptosis has been implicated in the pathogenesis of various neurodegenerative
      disorders, although the extent to which it is responsible for the
      neurodegeneration along with other kind of cell death events is not known.
      Eventhough much information is available today on the apoptotic cascades in
      general, the precise mechanism and the exact sequence of events leading to
      neuronal degeneration in Alzheimer's disease (AD) and other neurodegenerative
      disorders is not understood till now. Amyloid beta (Abeta) proteins are the
      hallmark toxic proteins known to cause the activation of apoptotic cascades via
      caspase dependent and caspase-independent pathways. Abeta can cause neuronal
      apoptosis through multiple mechanisms involving mitochondria and endoplasmic
      reticulum as the key organelles. In this review, we have discussed the role of
      apoptosis in neurodegeneration and provided new thoughts on the role of protein
      conformational dynamics and DNA integrity associated with neurodegenerative
      disorders. An insight on whether the apoptosis observed in the neurodegenerative
      disorders is of any functional advantage has been discussed.

PMID- 17017862
TI  - Role of metals in neuronal apoptosis: challenges associated with
      neurodegeneration.
AB  - Apoptosis is a tightly controlled process in which cell death is executed through
      activation of specific signalling pathways. Within cells, there are positive and
      negative regulatory pathways of apoptosis, hence it is targeted as 'Double-edged
      sword', the balance between these pathways dictates the cell fate. The past
      decade has seen intense focus on the mechanisms of apoptosis. Many important
      observations on the various signalling pathways mediating apoptotic cell death
      have been made and our understanding of the importance of apoptosis in both
      normal growth and development and patho-physiology has greatly increased. In
      addition, mechanisms of metal-induced toxicity continue to be of interest given
      the ubiquitous nature of these contaminants. The purpose of this review is to
      summarize our current understanding of the apoptotic pathways that are initiated
      by metals in Alzheimer's disease. Increased understanding of metal-induced
      (direct) and metal-amyloid-beta (indirect) linked neuronal cell death through the
      formation of reactive oxygen species (ROS) is critical to illuminate mechanisms
      of metal-induced cell death, as well as the potential role of metal speciation in
      neurodegeneration.

PMID- 17017863
TI  - Oxidative stress: apoptosis in neuronal injury.
AB  - Apoptosis has been well documented to play a significant role in cell loss during
      neurodegenerative disorders, such as stroke, Parkinson disease, and Alzheimer's
      disease. In addition, reactive oxygen species (ROS) has been implicated in the
      cellular damage during these neurodegenerative disorders. These ROS can react
      with cellular macromolecular through oxidation and cause the cells undergo
      necrosis or apoptosis. The control of the redox environment of the cell provides
      addition regulation in the signal transduction pathways which are redox
      sensitive. Recently, many researches focus on the relationship between apoptosis
      and oxidative stress. However, till now, there is no clear and defined mechanisms
      that how oxidative stress could contribute to the apoptosis. This review hopes to
      make clear that generation of ROS during brain injury, particularly in ischemic
      stroke and Alzheimer's Disease, and the fact that oxidative state plays a key
      role in the regulation and control of the cell survival and cell death through
      its interaction with cellular macromolecules and signal transduction pathway, and
      ultimately helps in developing an unique therapy for the treatment of these
      neurodegenerative disorders.

PMID- 17017864
TI  - Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer's
      disease.
AB  - Although oxidative stress and mitochondrial dysfunction have been linked to
      neurodegenerative diseases such as Alzheimer's disease (AD), it remains unclear
      how mitochondrial oxidative stress may induce neuronal death. In a variety of
      tissues, cumulative oxidative stress, disrupted mitochondrial respiration, and
      mitochondrial damage are associated with, and may indeed promote cell death and
      degeneration. In this review, we examine current evidence supporting the
      involvement of mitochondria and mitochondrially generated stress signaling in AD
      and discuss potential implications for the mechanism of pathogenesis of this
      disease. Mitochondria are pivotal in controlling cell life and death not only by
      producing ATP, and sequestering calcium, but by also generating free radicals and
      serving as repositories for proteins which regulate the intrinsic apoptotic
      pathway. Perturbations in the physiological function of mitochondria inevitably
      disturb cell function, sensitize cells to neurotoxic insults and may initiate
      cell death, all significant phenomena in the pathogenesis of a number of
      neurodegenerative disorders including AD.

PMID- 17017865
TI  - Molecular mechanisms of ischemic neuronal cell death--with relevance to
      Alzheimer's disease.
AB  - There are many similarities in molecular mechanisms of neuronal cell death
      observed in ischemic stroke and Alzheimer's disease. From point of organelle
      damage, we introduced molecular events seen in ischemic stroke, and compared the
      findings with that observed in Alzheimer's disease. In the brain after ischemia,
      transmembrane potential and ion gradient are disturbed at very early stage.
      Several drugs are aimed to minimize this change, some of which were effective in
      experimental models. Calcium blocker and glutamate antagonist were also effective
      for Alzheimer's disease. As for mitochondrial and endoplasmic reticulum damage,
      both disorders share common pathological findings such as pro-apoptotic signals
      activation. However, there are some molecules which are neuroprotective in
      Alzheimer's disease but pro-apoptotic in ischemic neurons. We need to be so
      careful for judging the significance of a phenomenon obtained by an experiment.
      Lysosome, called as suicide bag, play important roles both in the brain of
      ischemic stroke and Alzheimer's disease. Leak of lysosomal enzymes influence, at
      least partially, the fate of neurons under pathological conditions in both
      disorders.

PMID- 17017866
TI  - Amyloid beta peptide, 4-hydroxynonenal and apoptosis.
AB  - Considerable evidence suggests a role for oxidative stress in the pathogenesis of
      neuron degeneration in several neurodegenerative disorders including Alzheimer's
      disease (AD). Although debated, increasing evidence suggests that oxidative
      stress/damage (amyloid beta peptide, iron/hydrogen peroxide) or neurotoxic by
      products of lipid peroxidation (4-hydroxy-2-nonenal, acrolein) lead to cell death
      through apoptosis or programmed cell death in AD. This review discusses current
      evidence supporting the role of oxidative stress/damage mediated apoptosis in in
      vitro models of neurodegeneration.

PMID- 17017867
TI  - Genotoxicity in Alzheimer's disease: role of amyloid.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder pathologically
      identified by the presence of extracellular senile plaques (SP) with a
      proteinaceous core composed of aggregates of the amyloid peptide (Abeta) and
      intracellular aggregates of the microtubule-associated protein tau (tau) as
      neurofibrillary tangles (NFTs). These hallmarks consist of abnormally folded
      proteinaceous components that are believed to be neurotoxic in AD. The mechanisms
      of toxicity remain unclear although oxidative stress and inflammation are
      implicated as mediators of the toxicity and these lesions, in turn, are known to
      damage cellular components including proteins, lipids in the membrane and DNA.
      However effects on genotoxicity and its role in AD are less clear. The present
      review discusses various influences, in particular of amyloid, on the genetic
      material and their possible role in the neurodegeneration in AD. Further, the
      amalgamation of genomics and proteomics in understanding AD and therapeutic
      development is suggested.

PMID- 17017868
TI  - Challenges in neuronal apoptosis.
AB  - There are myriads of reasons and ways for a neuron to die, among which apoptosis
      is a specific form that is processed in two major signaling pathways, the TNF
      receptor-mediated (extrinsic) and the mitochondria-based (intrinsic) cell death
      pathway with several avenues of crosstalk between them. The molecular key players
      of apoptosis, the importance of the Csp cascade via interaction with different
      death effector domains and the role of the effector Csp-3 driving the execution
      of the cell death program are reviewed. Recent data suggest that caspases
      converge amyloid and tau Alzheimer pathologies: beta amyloid peptide activates
      caspases which on turn cleave tau and via phosphorylation of tau initiate tangle
      pathology in both Alzheimer disease and other tauopathies. Several mediators show
      a bifunctional regulation of apoptosis, with both pro- and anti-apoptotic
      activities. The latter modify the cell death pathway due to inhibition of Csp
      activation or other protective mechanisms and may delay it or, via abortive
      apoptosis ("abortosis") lead to prolonged survival of nerve cells. While the role
      of apoptosis in neurodegeneration is well documented in tissue culture and
      transgenic animal models, in human postmortem AD brain its occurrence and role
      are discussed controversially. Given the short duration required for the
      completion of apoptosis and the chronic progressive course of neurodegeneration
      in Alzheimer disease and related disorders, the detection of rare neurons
      displaying morphological signs of apoptosis and expression of the activated key
      executing enzyme Csp-3 is realistic, although there is significantly increased
      incidence of cells with DNA fragmentation, mainly glia, and markers for a
      "proapoptotic" environment in the aged human brain indicate increased
      susceptibility of neurons to metabolic and other noxious factors. Postmortem
      analysis can bridge some but not all of our knowledge gaps, but the results are
      still controversial, and we need a better understanding of the molecular basis
      and pathways that drive the yin-yang between neuronal survival and death.

PMID- 17017869
TI  - Apoptosis in Alzheimer disease: a mathematical improbability.
AB  - Neuronal cell dysfunction and death are cardinal features of Alzheimer disease
      and a great deal of effort is being expended not only to understand factors
      involved in the cause and progression of disease (i.e., disease initiators and
      propagators) but, ultimately, the precise mechanism by which neurons die (for
      want of a better word, the terminators). Understanding each and every component
      of the complex pathway that ultimately leads to disease (a clinical phenotype) is
      clearly of paramount importance for the development of effective therapeutic
      strategies. Of particular intrigue for many scientists, perhaps the more macabre
      among us, has been to decipher the final event - namely cell death. Broadly
      speaking, cell death falls into two categories, apoptotic and necrotic. The
      former, apoptosis, by definition, is a controlled event; thereby offering the
      potential for intervention, whereas necrosis is a more stochastic process. Since
      many of the propagators and exacerbators involved in Alzheimer disease are pro
      apoptotic, it is not surprising that certain aspects of apoptosis are evident.
      However, it would be a mistake to call this apoptosis. In fact, as reviewed
      herein, the chronic course of disease together with the necessarily slow rate of
      neuronal death makes apoptotic cell death in Alzheimer disease a mathematical
      improbability. The numbers simply do not add up.

PMID- 17017870
TI  - A commentary on neuronal degeneration and cell death in Guam ALS and PD: an
      evolutionary process of understanding.
AB  - The Twentieth Century witnessed tremendous advances in our understanding of
      neurodegenerative diseases. Not least among them were the contributions from
      hyperendemic foci of neurodegenerative disorders in isolated human groups
      worldwide, with the knowledge gained applicable to our understanding of related
      neurodegenerative diseases globally.

PMID- 17017871
TI  - Histone deacetylase inhibitors: a novel therapeutic approach to Huntington's
      disease (complex mechanism of neuronal death).
AB  - Huntington's disease is an autosomal dominantly inherited neurodegenerative
      disorder caused by a polyglutamine repeat expansion. The onset of HD leads to
      problems with movement, cognition, and behavioral functioning and there is
      currently no effective treatment. The mechanism by which mutant huntingtin causes
      neuronal dysfunction is not known. However, multiple pathologic mechanisms have
      been discovered. Recent studies provide strong evidence for transcriptional
      dysregulation as a mechanism of HD pathogenesis. The control of eukaryotic gene
      expression depends on the modification of histone proteins associated with
      specific genes; acetylation and deacetylation of histones play a critical role in
      gene expression. Studies in numerous HD models have shown that mutant huntingtin
      expression leads to a change in histone acetyl transferase (HAT) activity and
      suggest that aberrant HAT activity may be an underlying mechanism of
      transcriptional dysregulation in HD. Furthermore, recent studies have shown a
      therapeutic role for histone deacetylase (HDAC) inhibitors in a number of HD
      models. In this review we discuss a number of studies that use HDAC inhibitors as
      therapeutic agents in HD models. These studies demonstrate that HDAC inhibitors
      are a promising therapeutic approach for the treatment of HD.

PMID- 17017872
TI  - Knowledge of epigenetic influence for prostate cancer therapy.
AB  - Prostate cancer is one of the most prevalent cancers in men in many countries,
      increasing in frequency with age through the most advanced years. The standard
      treatment for newly diagnosed metastatic tumors is androgen ablation. However,
      advanced prostate cancer nevertheless often develops in many cases. Although
      hormonal manipulation and chemotherapy have uncertain value for advanced lesions,
      especially androgen-independent, recent studies of docetaxel-based chemotherapy
      in men with androgen-independent prostate cancer have shown a survival benefit.
      Intensive investigations have shown that aberrant epigenetic features. including
      aberrant DNA methylation, make an important contribution to carcinogenesis as
      well as genetic alterations. Hypermethylation of CpG islands in promoter regions
      can lead to silencing of tumor-suppressor genes, while hypomethylation of the
      genome leads to instability. This review attempts to provide up-to-date
      information regarding the significance of epigenetics for human prostate cancer,
      with aberrations offering dues to therapy and possibly also providing targets for
      anticancer drugs.

PMID- 17017873
TI  - Development and assessment of conventional and targeted drug combinations for use
      in the treatment of aggressive breast cancers.
AB  - Combination chemotherapy has been at the forefront of cancer treatment for over
      40 years. However, the rationale for selecting drug combinations and the process
      used to demonstrate clinical effectiveness has primarily followed trial and error
      methodology. Typically, the selection and assessment of combined drug therapies
      has been based on the effectiveness of each agent as monotherapy in treating the
      neoplasm and avoiding overlapping toxicities, followed by clinical trials to
      establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is
      inefficient in terms of the time required to complete and revise these clinical
      trials based on the outcome to optimize the drug combination. A more rational
      approach for the development of combination oncology products should consider (i)
      in vitro assays for assessing therapeutic effects of drug combinations
      (antagonistic, additive or synergistic interactions) when added simultaneously;
      (ii) methods for measuring these interactions in vivo; (iii) the importance of
      understanding pharmacokinetic and biodistribution parameters when using drug
      combinations; (iv) the need to assess pathways known to contribute to cancer cell
      survival as well as metastasis; and (iv) the need to assess the fate of different
      cell populations (cancer and stroma) contributing to the development of cancer.
      Therefore, the goal of this article is to provide a road map for the preclinical
      development of drug combination products that will have improved therapeutic
      activity and a high likelihood of providing beneficial therapeutic outcomes in
      patients with aggressive cancers with a specific focus on patients with breast
      cancer.

PMID- 17017874
TI  - Synthetic glycopeptides from the mucin family as potential tools in cancer
      immunotherapy.
AB  - Compared to glycoproteins of healthy cells, glycoproteins of tumor cells are
      often aberrantly glycosylated. Thus, glycopeptide fragments of surface
      glycoproteins of tumor cells are of interest as tumor-associated antigens for the
      distinction between normal and tumor cells. Cancer immunotherapy directed at
      selectively targeting these tumor-associated glycoprotein structure alterations-
      deficient glycosylation and, thus, exposure of peptide epitopes which are masked
      in normal cells--is considered a promising approach for the treatment of cancer.
      For this purpose, glycoproteins from the mucin family are of particular interest.
      Mucins belong to a class of heavily O-glycosylated, high-molecular weight
      glycoproteins present on the surface of many epithelial cells. The mucin core
      protein consists of numerous tandem repeats rich in serine, threonine and
      proline. In their tumor-associated forms, epithelial mucins carry cryptic
      saccharide structures such as T(N)-, T-, sialyl-T(N)- and sialyl-T antigens and
      more complex oligosaccharides (e.g. Lewis(y)). In contrast to glycoproteins
      isolated from natural sources, synthetic glycopeptides can be obtained in high
      purity and with exactly defined structure. In this review, methodologies for the
      synthesis of mucin-type glycopeptides containing complex tumor-associated antigen
      structures are described. Due to the low immunogenicity often exhibited by
      synthetic tumor-associated glycopeptide antigens, their conjugation to carrier
      proteins or suitable T-cell epitopes is essential for the development of anti
      tumor vaccines. The results of immunological evaluations of synthetic
      (glyco)peptides and oligosaccharides are described. Some of these synthetic
      vaccines show promising activities inducing proliferation of T-cells and
      cytotoxic T-cell responses.

PMID- 17017875
TI  - Protein tyrosine phosphatases, new targets for cancer therapy.
AB  - Cellular growth and development are regulated by reversible phosphorylation of
      tyrosine residues in target proteins. Protein tyrosine phosphatases (PTPs)
      catalyse removal, and protein tyrosine kinases (PTKs) the addition of phosphate.
      Data from various sources support a role for PTKs in transformation and it has
      long been hypothesized that some PTPs will function as tumour suppressor genes.
      Specific PTPs are down-regulated in some tumours, sometimes in association with
      ectopic expression of PTKs. Alternatively, other PTPs dephosphorylate and
      activate PTKs, and are themselves oncogenic. Much current interest surrounds the
      clinical introduction of specific PTK inhibitors, whereas targeting of PTPs
      remains largely unexplored. Phosphatases represent 4% of the drugable human
      genome and PTPs appear an important new target for cancer therapy. Here we
      briefly, describe PTP structure and function. Secondly, we review experimental
      and clinical data, which support a role for PTPs in neoplastic development. Next,
      we review current strategies for generation of agents targeting PTPs; these
      include re-expression of tumour suppressor genes (mediated via adenoviral
      vectors), and generation of small molecules designed to inhibit oncogenic
      activity. Finally, we address the role of PTPs in melanoma, an increasingly
      common tumour that may represent an appropriate target for therapeutic
      manipulation of PTP activity.

PMID- 17017876
TI  - Implications of somatic mutations in the AML1/RUNX1 gene in myelodysplastic
      syndrome (MDS): future molecular therapeutic directions for MDS.
AB  - Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells
      characterized by ineffective and inadequate hematopoiesis. MDS is also a
      susceptibility to acute myeloid leukemia (AML) and shown to be extremely
      resistant to current therapeutic strategies. MDS in a subset of 10-20% of
      patients arise after previous chemotherapy or radiation exposure for other
      malignancies. Because MDS is a heterogeneous disorder, specific gene
      abnormalities playing a role in the myelodysplastic process have been difficult
      to identify. Cytogenetic abnormalities are seen in half of MDS patients, and
      generally consist of partial or complete chromosome deletion or addition, whereas
      balanced translocations are rare. Genes more frequently implicated in the
      pathogenesis of MDS remain unknown. Although point mutations of critical genes
      have been demonstrated to contribute to the development MDS, there was no strong
      correlation between these mutations and clinical features. Recently, we reported
      the high incidence of somatic mutations in the AML1/RUNX1 gene, which is a
      critical regulator of definitive hematopoiesis and the most frequent target for
      translocation of AML, in MDS, especially refractory anemia with excess blasts
      (RAEB), RAEB in transformation (RAEBt) and AML following MDS (defined here as
      MDS/AML). The MDS/AML patients with AML1 mutations had a significantly worse
      prognosis than those without AML1 mutations. Most of AML1/RUNX1 mutants lose
      trans-activation potential, which leads to a loss of AML1 function indicating
      that AML1/RUNX1 dysfunction is one of the major pathogenesis of MDS/AML.
      Normalizing AML1 function or regulating cooperative gene mutations would provide
      an important clue for molecular target therapies.

PMID- 17017877
TI  - Combinatorial approaches to iminosugars as glycosidase and glycosyltransferase
      inhibitors.
AB  - Oligosaccharide processing enzymes such as glycosidases and glycosyltransferases
      are important classes of biocatalysts involved in synthesising specific
      oligosaccharide structures on proteins and lipids. These enzymes are known to be
      involved in a wide range of important biological processes, such as intestinal
      digestion, post-translational processing of glycoproteins, lysosomal catabolism
      of glycoconjugates and inter-cellular recognition events. Inhibition of these
      enzymes can disrupt biosynthesis of oligosaccharides, thus interfering in all of
      these processes. Hence, "glyco-enzyme" inhibitors might have enormous therapeutic
      potential in many diseases such as viral infection, cancer and diabetes. This
      very important prospect has led to increasing interest and demand for these
      compounds. Interference in oligosaccharide processing is the basis for the anti
      influenza neuraminidase inhibitors that have recently been marketed and also for
      the potential use of glycosidase inhibitors against HIV, Gaucher's disease,
      hepatitis, and cancer. Since a rational design and synthesis of inhibitors are
      often extremely difficult due to the limited information regarding the structure
      of the active site, combinatorial approaches are particularly promising. This
      review will focus on synthetic efforts for the preparation of combinatorial
      libraries of glyco-enzyme inhibitors.

PMID- 17017878
TI  - Combinatorial synthesis and screening of novel odorants such as polyfunctional
      thiols.
AB  - Combinatorial chemistry was shown to be an efficient tool for the preparation of
      new aroma-impact compounds. In this case, polyfunctional thiols were synthesized
      quickly using halide reagents or Bunte salt intermediates. They were separated by
      gas chromatography and then characterized using low resolution EI and CI mass
      spectrometry. The individual sensorial properties of the thiol products (i.e.
      odor and perception threshold) were determined by GC-O (olfactometry) which uses
      the human nose as detector. The thiols were characterized based on their
      particular odors. 3-Methyl-2-buten-1-thiol, a relevant flavor naturally present
      in beer and coffee, emerged as the most powerful of the thiol library.

PMID- 17017879
TI  - LNA-modified oligodeoxynucleotide hybridization with DNA microarrays printed on
      nanoporous membrane slides.
AB  - We report a robust method for the detection of hybridization events using a
      microarray-based assay on a nanoporous membrane platform. The technique is
      characterized by a hybridization time of only 1 hour and uses Cy5-labeled, 7-mer
      oligodeoxynucleotide probes modified with locked nucleic acid (LNA) nucleotides.
      We show that the volume of the DNA spotted onto a nanomembrane can be reduced to
      approximately 4 nL with detectable signal intensity. Moreover, the amount of the
      DNA target could be reduced to 4 fmol. The described approach could dramatically
      increase the throughput of techniques based on sequencing by hybridization, such
      as oligofingerprinting, by decreasing the total number of probes that are needed
      for analysis of large clone sets and reduction of the sample/reagent consumption.
      The method is particularly advantageous when numerous hybridization-based assays
      must be performed for characterization of sample sets of 100,000 or more.

PMID- 17017880
TI  - Inhibition of lethal endotoxin shock with an L-pyridylalanine containing
      metalloproteinase inhibitor selected by high-throughput screening of a new
      peptide library.
AB  - Gelatinase B/MMP-9 fulfills crucial regulator or effector functions in disease
      states and may be pharmacologically targeted by specific inhibitors. The
      characteristics of cleavages of a natural gelatinase B substrate were simulated
      and amino acids with zinc-ion chelating side-groups were employed to design a
      library of peptide-based inhibitors. Here, we extend previous findings of
      combinatorial chemical synthesis and subsequent library deconvolution with a
      recently established high-throughput technology. This enabled us to study MMP
      inhibitors with two zinc-binding groups and to identify a new L-pyridylalanine
      containing gelatinase B inhibitor. The peptide analog was found to inhibit,
      almost to the same degree, the neutrophil enzymes collagenase 2/ MMP-8 and MMP-9
      and the monocytic tumor necrosis factor-alpha (TNF-alpha) converting enzyme
      (TACE/ADAM-17) in vitro and to protect mice against lethal endotoxinemia in vivo.
      These data illustrate the usefulness of the screening platform for protective
      inhibitor discovery and complement recent insights in the pathogenesis and
      treatment of shock syndromes.

PMID- 17017881
TI  - Development and optimization of a non-radioactive JNK3 assay.
AB  - In light of emerging interest in the relevance of c-Jun NH2-terminal protein
      kinase 3 (JNK3) as a promising drug target, we describe here an advanced non
      radioactive immunosorbent JNK3 activity assay that is applicable for routine
      screening of small molecule ATP-competitive enzyme inhibitors. We modified and
      established a JNK3/ATF-2 protocol based on our previously described p38 MAPK
      method [1] for a substrate-bound non-radioactive procedure that represents a
      convenient alternative to conventional radioactive protein kinase assays. The
      objective of the present study was to validate these conditions by using the
      reference compounds SP600125 and SB203580 to achieve comparable IC(50) results to
      published data. Furthermore, an IC(50) for staurosporine was determined. The
      protocol we describe here represents an accessible and robust screening assay for
      JNK3 inhibitors.

PMID- 17017882
TI  - DNA and RNA aptamers: from tools for basic research towards therapeutic
      applications.
AB  - The systematic evolution of ligands by exponential enrichment (SELEX) is a
      combinatorial oligonucleotide library-based in vitro selection approach in which
      DNA or RNA molecules are selected by their ability to bind their targets with
      high affinity and specificity, comparable to those of antibodies. Nucleic acids
      with high affinity for their targets have been selected against a wide variety of
      compounds, from small molecules, such as ATP, to membrane proteins and even whole
      organisms. Recently, the use of the SELEX technique was extended to isolate
      oligonucleotide ligands, also known as aptamers, for a wide range of proteins of
      importance for therapy and diagnostics, such as growth factors and cell surface
      antigens. The number of aptamers generated as inhibitors of various target
      proteins has increased following automatization of the SELEX process. Their
      diagnostic and therapeutic efficacy can be enhanced by introducing chemical
      modifications into the oligonucleotides to provide resistance against enzymatic
      degradation in body fluids. Several aptamers are currently being tested in
      preclinical and clinical trials, and aptamers are in the process of becoming a
      new class of therapeutic agents. Recently, the anti-VEGF aptamer pegaptanib
      received FDA approval for treatment of human ocular vascular disease.

PMID- 17017883
TI  - Modifications to increase the efficiency of the fluorometric cycling assay for
      cyclic ADP-ribose.
AB  - Cyclic ADP-ribose (cADPR) is an intracellular messenger that triggers the release
      of calcium ions from intracellular stores in a variety of cell types. The
      fluorometric cycling assay has become the preferred method for measuring cADPR
      due to its high level of sensitivity (in the sub-nanomolar range) and its use of
      commercially available reagents. Additionally, the assay is performed in
      multiwell plates, making it suitable for high throughput screening using a
      fluorescence plate reader. The findings reported in this paper present several
      problems that may be encountered during various stages of the assay, and provide
      solutions to these problems. Modifications to the assay address reduced recovery
      of sample and cADPR with removal of perchloric acid (PCA) using organic solvent,
      reduction in diaphorase activity with heat treatment, and effects on resorufin
      fluorescence by pH range. Using these modifications, we report an increase of
      approximately 15% in recovery of brain cADPR, and show that between-subject
      variability is greatly reduced. We hope that these observations will encourage
      more widespread application of this valuable assay.

PMID- 17017885
TI  - Cytotoxic potential of phenothiazines.
AB  - Phenothiazines, a kind of sulfur-containing tricyclic compounds, have diverse
      biological activities including tranquilizer, antibacterial, antitumor and
      antihelmintic activities due to the relatively lower cytotoxicity. Phenothiazines
      have been used for clinical treatments as psychotropics. In contrast to the
      psychotropic preparations, their information of other biological activities of
      phenothiazines and their related compounds has been limited. This review article
      summarizes the interaction with DNA (using quantum calculation), antitumor
      activity, differentiation or apoptosis-inducing activity, tumor necrosis factor
      (TNF)-induction, antiproliferative activity, radical scavenging activity,
      antimutagenic activity, antiplasmid activity, antibacterial activity, reversal of
      multidrug resistance (MDR), blast transformation activity of phenothiazines,
      benz[c]acridines and benzo[a]phenothiazines.

PMID- 17017886
TI  - Fluorescence studies of anti-cancer drugs--analytical and biomedical
      applications.
AB  - The fluorescence properties of anticancer drugs (ACDs), including steady-state
      native fluorescence, time-resolved fluorescence, fluorescence polarization,
      excimer and exciplex emission, laser-induced fluorescence (LIF) with one- or two
      photon excitation are reviewed, as well as the use of fluorogenic labels and
      fluorescent probes for the non-fluorescent ACDs. The interest of monitoring the
      fluorescence spectral changes to study the interactions of ACDs with
      biomolecules, such as DNA, proteins, vesicles, and the formation of complexes is
      discussed. The fluorescence methodologies used for ACDs studies, including
      fluorescence with two-photon excitation, liquid chromatography and capillary
      electrophoresis with fluorescence and laser-induced fluorescence (LIF) detection,
      and fluorescence microscopy, are also surveyed. Analytical and bioanalytical
      applications of fluorescence, indicating good selectivity and very low limits of
      detection at the nanomolar and picomolar level for most ACDs, are described.
      Biomedical and clinical applications of the fluorescence methods, mostly oriented
      towards the evaluation of the cytoxicity and anti-tumor potential of ACDs in
      single cells as well as in biological fluids, including blood, serum, plasma,
      cerebrospinal fluid, urine and feces, are also discussed in detail. This review
      is based on selected literature published in the last decade (1994-2003).

PMID- 17017887
TI  - Luminescence and photophysical properties of benzo[a]phenothiazines--therapeutic,
      physico-chemical, and analytical applications.
AB  - Luminescence studies on a series of new 12H-benzo[a]phenothiazines (BPHTs),
      possessing potentially useful antitumor therapeutic properties, are reviewed. The
      electronic absorption and fluorescence spectral properties of BPHTs, as well as
      their triplet- and singlet-excited states luminescence quenching are reviewed.
      Ground-state and singlet-excited state dipole moments and solvatochromic
      relationships are also described for these compounds. Studies on the formation of
      inclusion complexes between BPHTs and cyclodextrins (CDs), including CD-enhanced
      fluorescence, and thermodynamic constants and molecular geometry of these
      complexes, are discussed. The BPHTs antitumor properties in relation to their pi
      electron density, and the physico-chemical and analytical applications based on
      their fluorescence and photophysical properties are also presented. This review
      article is based on selected literature data published in the last ten years
      (1993-2004).

PMID- 17017888
TI  - Interactions of phenothiazines with lipid bilayer and their role in multidrug
      resistance reversal.
AB  - The mechanism of multidrug resistance (MDR) reversal is not fully understood yet.
      Interaction of MDR modifiers with lipid bilayer of cell membranes and alterations
      of fluidity or other biophysical properties of plasma membrane might be an
      important factor in mechanism of MDR modulation and reversal. In this review we
      focus on phenothiazines which belong to the group of drugs known to modify MDR in
      different types of cells, from cancer cells up to various kinds of
      microorganisms. First, the aggregation properties of phenothiazines and their
      interactions with lipid bilayers are described. The localization of phenothazine
      derivative molecules in bilayers and alteration of membrane properties are
      discussed. Apart from the influence on model bilayers also the interactions of
      phenothiazines with cellular membranes (especially of erythrocytes) are reviewed.
      In subsequent sections the anti-MDR activity of phenothiazine derivatives
      observed in microorganisms and in cancer cells is described. The possible
      molecular mechanisms involved in MDR reversal by these compounds are presented.
      The direct interactions of phenothiazines with multidrug transporters and other
      effects of these modulators on plasma membranes are discussed. Finally, the
      structural features of phenothiazine derivatives essential for their optimal MDR
      reversal activity are described.

PMID- 17017889
TI  - Application of phenothiazine derivatives and other compounds for the
      determination of metals in various samples.
AB  - Phenothiazine derivatives (PDS) readily react with several metal ions in acid or
      buffer media to yield colored species which could be followed
      spectrophotometrically. Reaction conditions have been optimized to get colored
      species of maximum stability and intensity. The effects of foreign ions have been
      investigated. The results of all the methods were supported by statistical
      analysis. The proposed methods have been successfully applied for the analysis of
      various samples containing the interested metal ion(s). In addition, some
      extractive spectrophotometric methods based on the formation of ion-association
      complexes (extractable into organic solvents) and gravimetric methods have been
      discussed.

PMID- 17017890
TI  - Phenothiazines and structurally related compounds as modulators of cancer
      multidrug resistance.
AB  - Phenothiazines and structurally related compounds alongside their other
      biological activities are able to modulate multidrug resistance (MDR) in tumor
      cells. The extensive investigations on their MDR modulation effects consist part
      of the efforts to overcome MDR - the major obstacle in cancer chemotherapy. In
      this article we try to systematize the results collected in the last two decades
      in two main aspects. The first one comprises the mechanism of modulation by
      phenothiazine-type MDR modulators. Two main possible mechanisms of MDR reversal
      are reviewed: (i) direct interaction with Pgp; (ii) interactions with membrane
      phospholipids. The second aspect relates to the structural properties of
      phenothiazines and related compounds responsible for their MDR reversing effect.
      The structural alerts and physicochemical properties influencing anti-MDR
      activity are considered as identified by structure--activity (SAR) or
      quantitative structure--activity relationship (QSAR) studies. Results discussed
      in the article point to MDR modulation by phenothiazines and related compounds as
      a complex process in which more than one mechanism are certainly involved.
      Further investigations in this direction should contribute to elucidation of the
      possible mechanisms of MDR modulation by these compounds. On the basis of the
      studies discussed the potential use of phenothiazine-type MDR modulators as a
      model system in the further investigations of the MDR phenomenon is outlined.

PMID- 17017891
TI  - Photosensitization of biomolecules by phenothiazine derivatives.
AB  - It is well known that many drugs act as photosensitizers towards cells by
      interacting with various cellular components such as lipids, proteins and nucleic
      acids. The structural modifications of the cellular components may occur by
      direct interactions of the excited states (singlets or triplets) of the drugs
      with the biological substrate or indirectly, through reactive species of oxygen
      sensitised by the drug themselves. In particular, the phototoxic activity of
      various drugs correlated with their potential photomutagenic and
      photocarcinogenic effects, takes place through DNA modification. Phenothiazines,
      a class of antihistaminic (anti-H1) or neuroleptic drugs used in the therapy of
      mental illness, such as schizophrenia, organic psychoses and other mental
      disorders, are known to induce photosensitization of the skin by systemic use or
      by topical applications as antiallergic drugs. In this review we have focused our
      attention on the photosensitizing property of phenothiazines and related
      compounds both in vitro and in vivo systems. Particular attention has been given
      to the mechanism of photo reaction with biomolecules such as lipids, proteins and
      DNA. Moreover there is a growing interest in drugs having photobiological effects
      because of their possible application as phototherapeutics. It has been
      interesting in this context to mention briefly the possible application of
      phenothiazine derivatives as new photosensitizers for their therapeutic
      application in photodynamic therapy (PDT) or in the light inactivation of viruses
      and bacteria.

PMID- 17017892
TI  - Trypanosoma cruzi dihydrolipoamide dehydrogenase as target for phenothiazine
      cationic radicals. Effect of antioxidants.
AB  - Myeloperoxidase (MPO), myoglobin (Mb) and horseradish peroxidase (HRP), catalyzed
      the generation of radical-cations by one-electron oxidation of phenothiazines
      (PTZ). The transient formation of these radicals (PTZ+.) was confirmed by ESR and
      optical spectroscopy. These species are reactive towards Trypanosoma cruzi LADH
      (T. cruzi LADH), T. cruzi trypanothione reductase (T. cruzi TR) and possibly
      other macromolecule targets. Both T. cruzi enzymes were irreversibly inactivated.
      T. cruzi LADH inactivation depended on: a) PTZ structure, peroxidase nature and
      the rate production of PTZ+. radical cations; b) incubation time; c) the presence
      of an antioxidant that intercepts free radicals. The production of PTZ+. radical
      cations, which is essential for T. cruzi LADH inactivation, is correlated with
      the electron donor ability of the substrates, as qualified by the Hammett
      sigmapara constant for the subtituent in the 2-position of the PTZ. Promazine
      (PZ), trimeprazine (TMPZ) and thioridazine (TRDZ) were the most effective
      inactivating agents, whereas trifluophenothiazines with CF3 group at 2-position
      (Trifluoperazine (TFP), fluphenazine (FFZ) and trifluopromazine (TFPZ)), and
      propericyazine (PCYZ) with CN group at 2-position, were much less active or
      inactive, all in close agreement with their higher or lowest electron donor
      ability, respectively. Comparison of inactivation values for T. cruzi LADH and
      mammalian heart LADH demonstrated a greater sensitivity of T. cruzi LADH to
      various PTZ studied. Thiol compounds, tyrosine, dopa, tryptophan, NADH, ascorbate
      and trolox prevented T. cruzi LADH inactivation by the peroxidase/H2O2 systems in
      agreement with their ability to suppress PTZ+. radical cations. The role of these
      radicals as enzyme inhibitors, or as generators of secondary free radicals and
      metabolite depletors may contribute to explain the trypanocidal effect as well as
      other chemotherapeutic actions of PTZ.

PMID- 17017893
TI  - Phenothiazine: the parent molecule.
AB  - Phenothiazine is an aromatic tricyclic compound that first emerged from the
      furtive chemical activity surrounding the aniline dye industry at the latter half
      of the 19th century. It contains both nitrogen and sulphur atoms and is the
      parent molecule of a multitude of drugs that have enjoyed varied and extensive
      use throughout medical and veterinary practice. The compound itself is not
      without biological activity and has been shown to possess insecticidal,
      antifungal, antibacterial and anthelmintic properties. It was this latter
      vermifugal application that has earned the molecule a place alongside penicillin
      and DDT for its colossal impact on mankind. Following its extensive usage over
      many years, unwanted reactions including neuromuscular incoordination,
      photosensitization and haemolytic anaemia have been reported and these have
      limited its use in the present climate. Investigations into the mode of action of
      phenothiazine and its underlying biochemical properties have been undertaken but
      the molecule has yet to reveal its secrets and still poses problems of
      understanding at the molecular level. This article reviews the literature, both
      established and current, and presents a contemporary view on phenothiazine and
      its interaction with biological systems.

PMID- 17017894
TI  - Psychotropic medications and leukopenia.
AB  - Neutropenia and/or agranulocytosis are among the medicinal side-effects induced
      by many psychotropic drugs. Clozapine and carbamazepine cause the highest
      incidence of this side-effect and require long-term blood cell monitoring. Bone
      marrow suppression can have an allergic, hypersensitivity etiology (e.g.,
      clozapine), which mandates the causative drug discontinuation. It can also be a
      direct, toxic effect (e.g., carbamazepine), which calls for dosage reduction or a
      medication change. Other treatment options may include filgrastim, sargramostim,
      or lithium. Blood cell count monitoring is encouraged on patients receiving
      clozapine as long as the drug is continued. Such evaluation is also advised on
      those medicated with other psychotropics, especially carbamazepine.

PMID- 17017895
TI  - The guanylyl cyclase inhibition by MB as vasoplegic circulatory shock
      therapeutical target.
AB  - There were strong evidences that NO has capital importance in the progressive
      vasodilatation that associates to the varied circulatory shock forms. The
      decreased systemic vascular resistance observed in irreversible hemorrhagic
      (hypovolemic) and septic shock may be due to the excess production of nitric
      oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS)
      and ischemia reperfusion injury (cardiogenic shock, organ transplants), may
      involve nitric oxide overproduction. In these situations, the nitric oxide
      induced loss of vascular sensitivity to catecholamines and myocardial depression
      contributes to lethal hypotension. As NO vasodilatation is cyclic GMP-mediated,
      there were two therapeutical options: a) The unspecific NO synthesis inhibition
      by L-arginine analogs, iNOS-specific inhibition by corticoids and/or
      aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis
      inhibition is associated to tissue necrosis and adverse hemodynamic effects and
      its clinical use was associated with high mortality, the second option using MB
      is safer and more rational. The elaboration of this text was motivated to suggest
      the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock
      therapeutical target.

PMID- 17017896
TI  - Evolution of antipsychotic intervention in the schizophrenic psychosis.
AB  - The accidental discovery (in the 1950s) and subsequent development of
      antipsychotic drugs have revolutionized the care of many patients with the
      schizophrenic psychoses. The first-generation antipsychotics, though effective
      for hallucinations, delusions, as well as a treatment of the disorder in two
      thirds of patients with schizophrenia, burdened many patients with extrapyramidal
      effects (EPS), including dystonias, akathisia, and pseudo-Parkinsonian morbidity.
      Moreover, they had little or no effect on the most disabling, core symptoms
      associated with withdrawal of interests and interpersonal relationships. The
      second-generation antipsychotics, which began to appear in the late 1980s with
      the introduction of clozapine, had strikingly less morbidity, contributing little
      or no EPS and providing at least modest promise of reduction of negative symptoms
      and enhancement of some aspects of cognition. However, some second-generation
      antipsychotics have induced considerable weight gain, and appear to lower the
      threshold for the development of the metabolic syndrome, which increases cardio
      vascular morbidity. The actual mechanism(s) of action of the antipsychotic drugs
      is still in dispute. Direct and indirect effects on dopamine transmission have
      been supported by much of the evidence. Direct blockade of dopamine hyperactivity
      and partial restoration deficient dopamine has been the standard explanation of
      their effects. However, dysfunctional intracellular signal transduction and
      dysfunction of myelin are emerging as competing pathologies upon which
      antipsychotics act. It is likely that the next generation of antipsychotics will
      act more directly and more specifically on such underlying neuropathology.

PMID- 17017897
TI  - Antipsychotic medications in the treatment of bipolar disorder.
AB  - Antipsychotic medications have been used to treat acute phases, and prevent
      relapses in, bipolar illness since their introduction into psychiatric practice.
      With the introduction of second generation antipsychotic medications, there has
      been renewed interest in the utility of this class of medications in managing
      manic-depression. It appears that all antipsychotic agents investigated have a
      potent acute antimanic property. This has been shown both in monotherapy and in
      combination with traditional mood stabilizing medications. The first generation
      antipsychotics appeared to worsen depression or induce a depressive-like state,
      but the second generation agents do not have this property and may have some
      antidepressant properties in bipolar patients. There is a dearth of controlled
      long term studies, but in open studies, both first and second generation agents
      appear to have a beneficial effect. Second generation antipsychotic agents appear
      to be a useful tool that may benefit bipolar patients. Adverse consequences of
      this group of medications appear to be the major limiting factors to their use.
      Antipsychotic medications play a very important role in the treatment of bipolar
      illness. This has become especially true since the introduction of second
      generation agents. There is a wealth of data documenting the use of these agents
      in bipolar mania. There are fewer studies examining relapse prevention. Finally,
      there are a small number of interesting studies suggesting utility in bipolar
      depression. This paper will critically review available randomized clinical
      trials utilizing antipsychotic agents in bipolar disorder.

PMID- 17017898
TI  - A critical review of rating scales in the assessment of movement disorders in
      schizophrenia.
AB  - Tardive dyskinesia (TD) has been recognised for nearly 50 years. It is associated
      with antipsychotic drugs and is usually persistent with no satisfactory
      treatment. It is believed to be under-documented in medical records. Many rating
      scales have been devised to measure TD. Studies have demonstrated variability
      between the rating scales on the measures of reliability and validity, the
      clinical setting used, the raters involved in the ratings and the provision of
      definitions and instructions. Scales that include too many items to be
      comprehensive become cumbersome and difficult to use. A compromise is to reduce
      the number of items and have add-in items for individual patients. A good example
      of this approach is the Abbreviated Dyskinesia Scale (ADS). Rating scales
      continue to be the best available methods to evaluate dyskinesia but in view of
      the shortcomings of validity, reliability and utility for clinical use, more
      efforts need to be done to improve current rating scales and to develop new ones.

PMID- 17017899
TI  - Assessment of selective homing and contribution to vessel formation of
      cryopreserved peripherally injected bone marrow mononuclear cells following
      experimental myocardial damage.
AB  - In view of a potential clinical use we aimed this study to assess the selective
      homing to the injured myocardium and the definitive fate of peripherally injected
      labeled and previously cryopreserved Bone Marrow Mononuclear cells (BMMNCs). The
      myocardial damage (cryoinjury) was produced in 59 rats (45 treated, 14 controls).
      From 51 donor rats 4.4 x 10(9) BMMNCs were isolated and cryopreserved (slow
      cooling protocols); the number of CD34+ and the viability of pooled cells was
      assessed by flow-cytometry analysis before and after cryopreservation and
      simulated delivery through a 23G needle. Seven days after injury, BMMNCs were
      thawed, labeled with PKH26 dye and peripherally injected (20 x 10(6) cells in 500
      microl) in recipient rats. Two weeks after experimental injury, the heart, lungs,
      liver, kidneys, spleen and thymus were harvested to track transplanted cells.
      Except a small amount in the spleen, PKH26+ cells were found only in the
      infarcted myocardium of the treated animals. Typical vascular structures CD34+
      were found in the infarcted areas of all animals; treated rats showed a
      significantly higher number of these structures if compared with untreated.
      Morphological ultra-structural examination of infarcted areas confirmed in
      treated rats the presence of early-stage PKH26+ vascular structures derived from
      injected BMMNCs. The estimated mean CD34+ cells loss due to the cryopreservation
      procedure and to the system of delivery was 0.24% and 0.1%, respectively,
      confirming the feasibility of the procedure. This study supports the possible
      therapeutic use of cryopreserved peripherally injecetd BMMNCs as a source of
      CD34+ independent vascular structures following myocardial damage.

PMID- 17017900
TI  - Nutritional control, gene regulation, and transformation of vascular smooth
      muscle cells in atherosclerosis.
AB  - Contractile-state smooth muscle cells (SMC), the only cell type in the arterial
      media, undergoes migration to the intima, proliferation, and abundant
      extracellular matrix production during the early stages of atherosclerosis. This
      involves the ingestion of low-density lipoprotein (LDL) and modified or oxidised
      LDL by macrophages together with SMC by several pathways including a scavenger
      pathway leading to accumulation of cholesterol esters and formation of foam
      cells. High-plasma cholesterol levels constitute a major causative risk for
      atherosclerosis. The membrane-bound transcription factor called sterol regulatory
      element binding protein (SREBP) activates gene-encoding enzymes of cholesterol
      and fatty acid biosynthesis. The SREBP expression, in response to diet, shows
      that are involved in both lipogenesis and cholesterol homeostasis, moreover
      SREBPs are regulated directly by cholesterol. Animal models were used in trials
      of atherosclerosis, and cholesterol feeding has been described elsewhere as
      producing atherosclerotic lesions. We have examined the morphological, molecular
      and proliferative change in arterial SMC mimicking such a cholesterol diet, this
      transformed SMC is a good model to study the alterations of the differentiated
      state of SMC, and the transformation into foam cell, caused by cholesterol-rich
      diet. Despite the complexity of the interactions in atherosclerosis, there are
      many opportunities to affect the homeostatic balance of the artery wall at SMC
      levels. We have considered here some of the possible targets for intervention
      with promising strategies for the nutritional control of the genes, and, in a
      general way, the possibilities for modulating the expression of genes influencing
      atherosclerosis.

PMID- 17017901
TI  - Physiological and pharmacological insights into the role of ionic channels in
      cardiac pacemaker activity.
AB  - The generation of cardiac pacemaker activity is a complex phenomenon which
      requires the coordinated activity of different membrane ionic channels, as well
      as intracellular signalling factors including Ca(2+) and second messengers. The
      precise mechanism initiating automaticity in primary pacemaker cells is still
      matter of debate and certain aspects of how channels cooperate in the regulation
      of pacemaking by the autonomic nervous system have not been entirely elucidated.
      Research in the physiopathology of cardiac automaticity has also gained a
      considerable interest in the domain of cardiovascular pharmacology, since
      accumulating clinical and epidemiological evidence indicate a link between an
      increase in heart rate and the risk of cardiac mortality and morbidity. Lowering
      the heart rate by specific bradycardic agents in patients with heart disease
      constitutes a promising way to increase cardioprotection and improve survival.
      Thus, the elucidation of the mechanisms underlying the generation of pacemaker
      activity is necessary for the development of new therapeutic molecules for
      controlling the heart rate. Recent work on genetically modified mouse models
      provided new and intriguing evidence linking the activity of ionic channels genes
      to the generation and regulation of pacemaking. Importantly, results obtained on
      genetically engineered mouse strains have demonstrated that some channels are
      specifically involved in the generation of cardiac automaticity and conduction,
      but have no functional impact on the contractile activity of the heart. In this
      article, we will outline the current knowledge on the role of ionic channels in
      cardiac pacemaker activity and suggest new potential pharmacological targets for
      controlling the heart rate without concomitant negative inotropism.

PMID- 17017902
TI  - Development of monoclonal antibodies that inhibit platelet adhesion or
      aggregation as potential anti-thrombotic drugs.
AB  - Cardiovascular disease is the major cause of mortality in Western countries.
      Platelets play a crucial role in the development of arterial thrombosis and other
      pathophysiologies leading to clinical ischemic events. In the damaged vessel
      wall, platelets adhere to the subendothelium through an interaction with von
      Willebrand factor (VWF), which forms a bridge between subendothelial collagen and
      the platelet receptor glycoprotein (GP) Ib/IX/V. This reversible adhesion allows
      platelets to roll over the damaged area, decreasing their velocity and resulting
      in strong platelet activation. This leads to the conformational activation of the
      platelet GPIIb/IIIa receptor, fibrinogen binding and finally to platelet
      aggregation. As each interaction (collagen-VWF, VWF-GPIb and GPIIb/IIIa
      fibrinogen) plays an essential role in primary haemostasis, loss of either of
      these interactions results in a bleeding diathesis, implying that interfering
      with these interactions might result in an anti-thrombotic effect. Whereas
      GPIIb/IIIa antagonists indeed are effective anti-thrombotics, it has been
      suggested that drugs which block the initial steps of thrombus formation
      (collagen-VWF or VWF-GPIb interaction) might have advantages over the ones that
      merely inhibit platelet aggregation. In this review we will discuss and compare
      the development of monoclonal antibodies (moAbs) that inhibit platelet adhesion
      or platelet aggregation. The effect of the moAbs in in vitro experiments, in in
      vivo models and in clinical trials will be described. Benefits, limitations,
      current applications and the future perspectives in the development of antibodies
      for each target will be discussed.

PMID- 17017904
TI  - Vasculogenesis of the embryonic heart: contribution of nucleated red blood cells
      to early vascular structures.
AB  - During embryogenesis, coronary vessels develop via vasculogenesis and
      angiogenesis. Vasculogenesis is formation in situ of primary vessels from
      angioblasts - endothelial cell progenitors, and angiogenesis is formation of
      vessels from the existing ones. In the embryonic heart vasculogenesis precedes
      and overlaps angiogenesis and lasts till the end of the fetal life. What is
      unique about heart vasculogenesis is the fact that nucleated blood cells
      accompany early angioblasts in a spatiotemporal way. Morphologically these
      structures resemble yolk sac blood islands, thus, they have been called blood
      island-like structures. In addition, these early vascular structures (blood
      island-like) are found in the heart before coronary vessel system connects with
      the systemic circulation. We present the recent data regarding endothelial cell
      properties and derivation during coronary vessel formation and hypotheses
      concerning a source of blood cells in early vascular structures of the heart; the
      latter has received little attention in the literature. This review summarizes
      current knowledge on the endothelial cell origination from epicardial mesothelium
      or liver primordium. This review also focuses on blood cell contribution to
      coronary vessel vasculogenesis. The role of proepicardium in the epicardial cover
      formation and the epicardium as a source of cellular components of coronary
      vasculature and interstitial fibroblasts is presented. It seems that blood cells
      and angioblasts, which form the early vascular structures do not derive from the
      same hemangioblastic precursor.

PMID- 17017903
TI  - Novel agents to manage dyslipidemias and impact atherosclerosis.
AB  - Strong epidemiological evidence linked elevated levels of low-density lipoprotein
      cholesterol (LDL-C) to risk of atherosclerotic heart disease. As a consequence,
      LDL-C lowering has been the main goal of therapy to reduce cardiovascular risk
      for the past few decades and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors (statins) have become some of the most commonly prescribed drugs. In
      spite of the proven efficacy of these drugs, statins reduce cardiovascular events
      by only 30-40%. Epidemiological analyses clearly indicate that a significant
      portion of risk is linked to other particles such as low high-density lipoprotein
      cholesterol (HDL-C), high triglycerides and others. Furthermore, several
      quantitative coronary angiography studies showing regression of atherosclerosis
      and reduction in subsequent events utilized a combination of drugs effective on
      LDL-C as well as other lipoproteins. Hence, several new drugs are being
      investigated that affect more than the traditional LDL-C pathways. In this
      article, we review lipoprotein-modifying agents that have either been recently
      released, or are still in various phases of development. They include agents that
      reduce LDL-C levels by mechanisms other than HMG-CoA inhibition (such as
      cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase
      inhibitors, sterol-regulating binding protein cleavage activating protein
      ligands, microsomal triglyceride transfer protein inhibitors, LDL-C receptor
      activators and farnesoid X receptor antagonists) and agents that raise HDL-C
      cholesterol or improve cholesterol efflux (such as cholesterol ester transfer
      protein inhibitors, retinoid X receptor selective agonists, specific peroxisome
      proliferator-activated receptor (PPAR) agonists and estrogen like compounds).

PMID- 17017905
TI  - Determination of bioactive constituents in traditional Chinese medicines by CE
      with electrochemical detection.
AB  - This paper reviews the recent advances and the key strategies in capillary
      electrophoresis (CE) with electrochemical detection (ECD) for separating and
      detecting a variety of bioactive constituents in traditional Chinese medicines
      (TCMs). The subjects covered include the separation modes for the CE analysis of
      the constituents in TCMs, the CE-ECD system, the sample preparations of TCMs, the
      ECD of TCMs, the applications of CE-ECD in the determination of various bioactive
      constituents in Chinese medicinal materials and their preparations, the
      identification and differentiation of TCMs by CE-ECD, and future prospects. It is
      expected that CE-ECD will become a powerful tool in the herbal medicinal fields
      and will lead to the creation of truly routine devices for TCM analysis.

PMID- 17017906
TI  - Toll-like receptor (TLR) response tolerance: a key physiological "damage
      limitation" effect and an important potential opportunity for therapy.
AB  - Endotoxin tolerance is a well known phenomenon, described both in vivo and in
      vitro, in which repeated exposure to endotoxin results in a diminished response,
      usually characterised as a reduction in pro-inflammatory cytokine release. The
      mechanisms responsible for endotoxin tolerance have become clear in recent years
      as our understanding of the pathways through which endotoxin mediates its effects
      has increased. The principal cell surface receptor for the lipopolysaccharide
      (LPS) component of endotoxin is Toll-Like Receptor 4 (TLR-4), a member of a
      highly conserved family of receptors specific for highly conserved bacterial and
      viral components which play key roles in the early inflammatory response to
      pathogens. As our understanding of the part played by TLR-4 signalling in
      endotoxin has increased, so it has become clear that response tolerance occurs to
      other TLR ligands in addition to LPS/endotoxin. Clinically, endotoxin/TLR
      response tolerance is thought to play an important part in susceptibility to
      reinfection in patients treated for severe sepsis. Whilst this may have developed
      as a protective evolutionary mechanism to prevent death caused by overwhelming
      cytokine release in sepsis, in the modern era of antibiotics, vasopressors and
      organ support, undoing this downregulation or "re-booting" the immune system may
      be a useful therapeutic target in the post-septic patient. This should, however,
      be approached with caution as it is possible that endotoxin/TLR response
      tolerance is also a physiological regulatory mechanism in areas normally exposed
      to bacterial-derived TLR-ligands such as the gut and liver.

PMID- 17017907
TI  - The emergence of multiplexed technologies as diagnostic platforms in systemic
      autoimmune diseases.
AB  - In the last decade, there has been a rapid proliferation of new technologies that
      are capable of identifying an increasing spectrum of autoantibodies and other
      biomarkers in autoimmune diseases. These newer diagnostic technologies include
      line immunoassays, addressable laser bead immunoassays, microarrays in
      microfluidics platforms and nanobarcode particles. Multiplexed bead assays are a
      particularly robust platform because they are adaptable to the detection of a
      variety of disease specific biomarkers, such as autoantibodies, cytokines,
      adipokines, drugs, oligonucleotides and single nucleotide polymorphisms, Although
      many laboratories have adopted a variety of these diagnostic platforms to improve
      turn around times and meet budget constraints, there is an urgent need to ensure
      that the rapid adoption of new technologies is attended by an appropriate balance
      of assay sensitivity and specificity.

PMID- 17017909
TI  - In utero exposure to phthalates and fetal development.
AB  - The diesters of benzene-1,2-dicarboxylic (phthalic) acid, commonly known as
      phthalates, are a family of industrial compounds, primarily used as plasticizers
      in enormous quantities for a variety of industrial uses in the formulation of
      plastics. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used
      plasticizer. These plasticizers are not covalently bound to the polymer and leach
      out into the environment, thus becoming ubiquitous environmental contaminants.
      Cumulating evidence points out on the adverse effects of phthalate exposure
      during intrauterine life. Recently, it has been documented that in utero
      phthalate exposure is associated with a shorter duration of pregnancy. Phthalates
      induce and activate a subset of peroxisome proliferator-activated receptors
      (PPARs) and have an intrinsic pro-inflammatory activity, while some natural PPAR
      agonists induce cyclooxygenase (COX)-2 expression. To this regard, COX-2 is
      thought to be overexpressed in chorioamnionitis (CA), a fetal systemic
      inflammatory response syndrome and a leading cause of preterm birth. An adequate
      maternal dietary intake of essential fatty acids, well known anti-inflammatory
      agents, is indispensable to fetal development. Recently, it has been shown that
      phthalates alter the placental essential fatty acids (EFAs) homeostasis so
      potentially leading to abnormal fetal development. Likewise, a possible down
      regulation of COX-2 by omega-3 fatty acids has been suggested. As a consequence,
      maternal supplementation with omega 3 during pregnancy could counteract the
      adverse effects of phthalates exposure in the human fetus. Here, we analyze the
      existing evidence on the link between antenatal phthalate exposure and abnormal
      fetal development, as well as on possible therapeutic tools to fight the adverse
      effect of this exposure.

PMID- 17017908
TI  - Comprehensive comparison of trace metal concentrations in cancerous and non
      cancerous human tissues.
AB  - The roles of metals in the development and inhibition of cancer have a complex
      character and have risen many questions because of their essential and toxic
      effects on human health. Question of whether trace metal concentrations in
      tissues are increased or decreased in cancerous patients in comparison with non
      cancerous patients has not been answered yet, due to the fact that the data known
      in this field is rare and have contradictory results. Although Zn and Cu
      concentrations in serum and tissues of cancerous patients have been extensively
      studied, the precise role of these metals in carcinogenesis is not clearly
      understood. On the other hand, the comprehensive review on trace metal
      concentrations in cancerous and non-cancerous tissues is uncommon. The
      differences in literature on the increases or decreases in trace metal
      concentrations of cancerous tissues in comparison with non-cancerous tissues may
      be attributed to a few reasons such as the tissue basis-dry or wet weight,
      different sensitivities and basis of analysis methods that affect the accuracy,
      and the difficulties in taking of the sample representing the cancerous or non
      cancerous area. In this study, the data published up to now have been reviewed.
      Comparison of results was done according to tissue and cancer types and trace
      metal species. The probable causes of differences in literature data were
      discussed. Especially, the published studies in recent years needed such a
      review.

PMID- 17017910
TI  - Drug excipients.
AB  - The therapeutical use of drugs involves the application of dosage forms, serving
      as carrier systems together with several excipients to deliver the active
      ingredient to the site of action. Drug delivery technology combines an
      understanding of medicinal chemistry and pharmacology with the skill of
      formulation, aiming the preparation of improved pharmaceuticals. The recently
      introduced Biopharmaceutical Classification System provides guidance for dosage
      form design, taking the molecular and physico-chemical properties of drugs into
      consideration through their solubility and permeability characteristics.
      Pharmaceutical excipients used for oral dosage form have been traditionally
      assumed as being inert. However, recent experience and new results have shown
      that they can interact with the active drug ingredient, affecting its
      dissolution, absorption and bioavailability. Classification of the excipients is
      based on their role in the pharmaceutical formulation and on their interactions
      influencing drug delivery, based on their chemical and physico-chemical
      properties. The main classes are the antioxidants, coating materials, emulgents,
      taste- and smell-improvers, ointment bases, conserving agents, consistency
      improvers and disintegrating materials. Some of the excipients may serve multiple
      purposes; for example, methylcellulose is a coating material, is applied in the
      preparation of suspensions, to increase viscosity, as a disintegrating agent or
      binder in tablets. The aim of this paper is to review the drug-excipients with
      respect to their chemistry, importance and interactions altering the
      pharmacokinetics of the drug substances. Emphasis will be given to two major
      classes of excipients: the antioxidants and disintegrants (substances
      facilitating disintegration of the drug tablets in the gastro-intestinal tract).
      Details will be given on the mechanisms through which they can alter drug
      effectiveness and tolerance, and control their application. Examples and
      references will be given for their analysis.

PMID- 17017911
TI  - N-acetylcysteine and other preventive measures for contrast-induced nephropathy
      in the intensive care unit.
AB  - The increase in diagnostic imaging procedures that require infusion of
      intravenous radiographic contrast has led to a parallel increase in the incidence
      of contrast-induced nephropathy (CIN). Since CIN accounts for a significant
      increase of hospital-acquired renal failure, length of stay and mortality,
      several additive strategies to prevent CIN are presently advocated, including N
      acetylcysteine (NAC), sodium bicarbonate, theophylline or fenoldopam, and peri
      procedural hemofiltration/hemodialysis. As only one (non-randomized) study has
      been performed in the intensive care setting, at present it is hard to give firm
      recommendations on preventive measures for CIN in intensive care patients.
      Indeed, future studies are needed to determine the true role of the above
      mentioned preventive measures in critically ill patients at risk for CIN. Since
      NAC has only few side-effects, we presently advise NAC as an additive preventive
      measure in the intensive care setting. Theophylline or sodium bicarbonate
      hydration are viable options, either in conjunction NAC or as alternatives.

PMID- 17017912
TI  - Natural products from plants as drug candidates and lead compounds against
      leishmaniasis and trypanosomiasis.
AB  - Millions of people in the developing world are affected by diseases caused by the
      kinetoplastid parasites: the leishmaniases, African trypanosomiasis, and Chagas
      disease. In many cases the drugs employed for treatment are toxic, marginally
      effective, given by injection, and/or compromised by the development of
      resistance. Since safe, effective, and affordable chemotherapeutic agents for
      leishmaniasis and trypanosomiasis are clearly needed, the identification of new
      antikinetoplastid drug candidates should be an urgent priority. Numerous plant
      derived natural products from different structural classes have been investigated
      as antileishmanial and antitrypanosomal candidates, including various alkaloids,
      terpenoids, flavonoids, and quinonoids. This review outlines the
      antikinetoplastid activities of plant-derived natural products reported in the
      literature and also provides an overview of mechanistic studies that have been
      conducted with these compounds. Given the activities of these agents and their
      diverse range of effects on parasite biology, natural products are a potentially
      rich source of drug candidates and leads against leishmaniasis and
      trypanosomiasis.

PMID- 17017913
TI  - Always around, never the same: pathways of amyloid beta induced neurodegeneration
      throughout the pathogenic cascade of Alzheimer's disease.
AB  - There is an increasing amount of evidence showing the importance of intermediate
      aggregation species of amyloid beta (Abeta) in the pathogenic cascade of
      Alzheimer's disease (AD). Different Abeta assembly forms may mediate diverse
      toxic effects at different stages of the disease. Mouse models for AD suggest
      that intraneuronal accumulation of Abeta oligomers might be involved in AD
      pathogenesis at a very early stage of the disease. The detrimental effect of
      oligomeric Abeta on synaptic efficacy is suggested to be an early event in the
      pathogenic cascade. Also early neuronal responses as activation of the unfolded
      protein response are processes likely to be associated with the increased
      occurrence of oligomeric or low fibrillar Abeta in AD pathology. In later stages
      of AD pathology, the fibrillarity of Abeta increases, concomitantly with a
      neuroinflammatory response, followed by tau related neurofibrillary changes in
      end stage pathology. We will review recent findings in in vitro cell models, in
      vivo mouse models, and post mortem AD brain tissue in view of the effects of
      different Abeta peptide species on neurodegeneration during AD pathogenesis.
      Insight into the role of different Abeta species during AD pathogenesis is
      essential for the development of disease modifying drugs and therapeutical
      strategies.

PMID- 17017914
TI  - Targeting protein-protein interactions with small molecules: challenges and
      perspectives for computational binding epitope detection and ligand finding.
AB  - A promising way to interfere with biological processes is through the control of
      protein-protein interactions by means of small molecules that modulate the
      formation of protein-protein complexes. Although the feasibility of this approach
      has been demonstrated in principle by recent results, many of the small-molecule
      modulators known to date have not been found by rational design approaches. In
      large part this is due to the challenges that one faces in dealing with protein
      binding epitopes compared to, e.g., enzyme binding pockets. Recent advances in
      the understanding of the energetics and dynamics of protein binding interfaces
      and methodological developments in the field of structure-based drug design
      methods may open up a way to apply rational design approaches also for finding
      protein-protein interaction modulators. These advances and developments include
      (I) computational approaches to dissect binding interfaces in terms of energetic
      contributions of single residues (to identify "hot spot" residues), (II)
      prediction of potential binding sites from unbound protein structures, (III)
      recognition of allosteric binding sites as alternatives to directly targeting
      interfaces, (IV) docking approaches that consider protein flexibility and
      improved descriptions of the solvent influence on electrostatic interactions, and
      (V) data-driven docking approaches. Here, we will summarize these developments
      with a particular emphasis on their applicability to screen for or design small
      molecule modulators of protein-protein interactions.

PMID- 17017915
TI  - A chemical genetics approach for the discovery of apoptosis inducers: from
      phenotypic cell based HTS assay and structure-activity relationship studies, to
      identification of potential anticancer agents and molecular targets.
AB  - The approach of chemical genetics has been widely used to study biological
      systems and to discover new drugs, signaling pathways and targets. The current
      review focuses on the development and utilization of a cell- and caspase-based
      apoptosis induction assay for the discovery of apoptosis inducers. We began with
      the development of a cell based phenotypic assay, which was used for the
      identification of small molecules that exhibit apoptosis inducing activities,
      including N-phenyl nicotinamides, gambogic acid, indole-2-carboxylic acid
      benzylidene-hydrazides, 4-aryl-4H-chromenes and 3-aryl-5-aryl-1,2,4-oxadiazoles.
      Through medicinal chemistry and biological studies, in vivo active compounds were
      identified, such as MX116407 as a tumor vascular disrupting agent with potent in
      vivo anticancer activity. The molecular targets of in vivo active compounds were
      identified using reagents designed and synthesized based on the SAR, including
      the identification of tail-interacting protein 47 (TIP47), an insulin-like growth
      factor II (IGF II) receptor binding protein, as the molecular target of 3-aryl-5
      aryl-1,2,4-oxadiazoles; and Transferrin receptor I (TfR), a transmembrane protein
      that interacts with transferrin (Tf) for the transport of iron into cells, as the
      molecular target of gambogic acid. We demonstrated that chemical genetics is a
      very useful approach for anticancer drug research, from the discovery of
      potential drugs, to the understanding of signaling pathways and identification of
      druggable targets.

PMID- 17017916
TI  - Structural modelling of the human drug-metabolizing cytochromes P450.
AB  - The structural and functional aspects of cytochrome P450 (CYP) enzymes are
      reviewed in the light of current developments in X-ray crystallography and other
      physical evidence, together with recent findings on the regulation of, and
      polymorphisms in, the human drug-metabolizing CYPs. It is emphasized that the
      crystal structures of eukaryotic CYPs are particuarly useful for constructing
      homology models of the human enzymes associated with drug metabolism, and that
      these models can aid in the high-throughput screening of novel compounds destined
      for human exposure.

PMID- 17017917
TI  - Recent advances in computational prediction of drug absorption and permeability
      in drug discovery.
AB  - Approximately 40%-60% of developing drugs failed during the clinical trials
      because of ADME/Tox deficiencies. Virtual screening should not be restricted to
      optimize binding affinity and improve selectivity; and the pharmacokinetic
      properties should also be included as important filters in virtual screening.
      Here, the current development in theoretical models to predict drug absorption
      related properties, such as intestinal absorption, Caco-2 permeability, and blood
      brain partitioning are reviewed. The important physicochemical properties used in
      the prediction of drug absorption, and the relevance of predictive models in the
      evaluation of passive drug absorption are discussed. Recent developments in the
      prediction of drug absorption, especially with the application of new machine
      learning methods and newly developed software are also discussed. Future
      directions for research are outlined.

PMID- 17017918
TI  - Therapeutic potential of targeting the endocannabinoids: implications for the
      treatment of obesity, metabolic syndrome, drug abuse and smoking cessation.
AB  - Rimonabant (SR141716, Acomplia) has been described as an antagonist/inverse
      agonist at the cannabinoid receptor type 1 (CB1). It has been widely used as a
      tool to evaluate the mechanisms by which cannabinoid agonists produce their
      pharmacological effects and to elucidate the respective physiological or
      pathophysiological roles of the CB1 receptor. It has become increasingly clear
      that rimonabant can exert its own intrinsic actions. These may be viewed as
      evidence of either the inverse agonist nature of rimonabant or of tonic activity
      of the endocannabinoid system. To date, data obtained from clinical trials (RIO
      North America, RIO Europe and RIO Lipid) indicate that rimonabant may have
      clinical benefits in relation to its anti-obesity properties and as a novel
      candidate for the treatment of metabolic and cardiovascular disorders associated
      with overweight and obesity. Other clinical trials, such as the STRATUS study,
      have also shown that rimonabant may be effective in smoking cessation, and that
      the drug has a reasonable safety profile. Recently, it has been shown that
      rimonabant prevents indomethacin-induced intestinal injury by decreasing the
      levels of pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha), thus
      indicating that CB1 receptor antagonists might exhibit potential anti
      inflammatory activity in acute and chronic diseases.

PMID- 17017919
TI  - Breathing generation and potential pharmacotherapeutic approaches to central
      respiratory disorders.
AB  - Breathing is generated and controlled by a brainstem neuronal network. Both
      intrinsic and synaptic interactions are involved in respiratory rhythm generation
      and their contribution is state-dependent, changing with hypoxia and the
      neuromodulatory state. Cellular mechanisms involved in acute or chronic
      pathological conditions are still unknown. A dysfunction in the neuronal network
      that controls breathing may be involved in several respiratory disorders such as
      central sleep apnea, sudden infant death syndrome, congenital hypoventilation,
      and in some clinical conditions that produce breathing dysfunction such as drug
      induced respiratory depression, obesity hypoventilation syndrome, etc. Despite
      the fact that several drugs are currently used to treat these diseases, the
      probable effects of this pharmacotherapy on the central rhythm generator and on
      other neuronal networks related with breathing control is poorly understood.
      Here, we review the current pharmacological approaches in the treatment of
      respiratory disorders, such as acetazolamide, theophylline, aminophylline,
      progesterone, nitric oxide. Possible effects of these drugs on the central
      respiratory network are discussed and putative therapeutic targets for the
      development of future pharmacological therapies suggested.

PMID- 17017920
TI  - 3,4-DGE is important for side effects in peritoneal dialysis what about its role
      in diabetes.
AB  - Breakdown of glucose under physiological conditions gives rise to glucose
      degradation products (GDPs). GDPs are also formed during heat sterilization of
      glucose-containing peritoneal dialysis fluids (PD-fluids). In PD-fluids GDPs have
      been shown in many different in vitro assays to be responsible for adverse
      effects such as growth inhibition, and impaired leukocyte function and impaired
      wound healing of peritoneal mesothelial cells. They have been linked to changes
      in the peritoneal membrane as well as to the decline in residual renal function
      of PD-patients. In diabetes one of the GDPs, 3-deoxyglucosone (3-DG), has been
      proposed as responsible for side-effects rather the glucose itself. 3,4
      dideoxyglucosone-3-ene (3,4-DGE) was recently identified as the most bio-reactive
      GDP in PD-fluids. It exists in equilibrium with a pool of precursors, consisting
      of 3-DG but also of other hitherto unidentified GDPs. In PD-fluids the
      concentration of GDPs in this pool is 10-20 times as high as that of 3,4-DGE. In
      vitro 3,4-DGE induces caspase-dependent apoptosis of neutrophils and peripheral
      blood mononuclear cells. Such induction may explain immunosuppressive properties
      of 3,4-DGE and contribute to an impaired peritoneal antibacterial defense. 3,4
      DGE also induces renal cell apoptosis. This may explain the better preservation
      of residual renal function in PD patients not exposed to GDPs. The concentration
      of 3-DG increases with worsening glycemic control and has been implicated in the
      genesis of diabetic microangiopathy. As 3,4-DGE is much more bio-reactive than 3
      DG and as it may be easily recruited from the pool, it seems probable that 3,4
      DGE is the molecule involved in the diabetic lesions rather than 3-DG itself.
      Thus, 3,4-DGE might contribute to diabetic nephropathy and to the impaired
      antibacterial defenses in diabetics. Unraveling of the pool dynamics of the GDPs
      and the molecular mechanisms of GDP-mediated cell injury may provide new
      therapeutic insights in PD and diabetes.

PMID- 17017921
TI  - Protective effect of cyclosporin-A in spinal cord injury: an overview.
AB  - Cyclosporin-A (CsA) is a potent and selective immunosupressive agent that, due to
      its mechanism of action, may be used to inhibit both the inflammatory reaction
      and the synthesis of nitric oxide (NO), a well-known neurotoxic agent. By these
      means CsA may diminish overproduction of free radicals and secondarily, lipid
      peroxidation (LP), both observed after acute spinal cord (SC) injury. Studies
      performed on reliable experimental models, using a well-standardized CsA dosing
      scheme, showed that a low dose of this drug inhibits the expression and activity
      of constitutive and inducible nitric oxide synthases (NOS), two enzymes strongly
      involved in the production of NO after SCI. Likewise, this compound inhibits LP.
      This inhibition is equivalent to the one induced by methylprednisolone (MP) at a
      high dose, but without the deleterious effects of the latter upon the survival of
      the animals. Moreover, inhibition of LP by CsA significantly correlates with a
      decrease in the demyelination process at the epicenter of the lesion, a
      significant survival of neurons in the red nucleus and enhanced motor recovery in
      animals submitted to a severe SC contusion. CsA acts as a neuroprotector agent
      after SC injury; hence, this drug may be useful in the treatment of acute SCI.
      CsA deserves further study in experimental animal models and in humans.

PMID- 17017922
TI  - Levocetirizine: an update.
AB  - Histamine plays a prominent and diverse role in the pathophysiology of allergic
      disease and therapeutic intervention is therefore typically focused on blocking
      the effects of this biogenic amine. A new antihistamine, levocetirizine, is the R
      enantiomer of cetirizine dihydrochloride and like its parent compound undergoes
      minimal hepatic metabolism. Levocetirizine has pharmacodynamically and
      pharmacokinetically favourable characteristics, including high bioavailability,
      rapid onset of action, limited distribution and a low degree of metabolism.
      Clinical trials indicate that it is safe and effective for the treatment of
      allergic rhinitis and chronic urticaria with a minimal number of untoward
      effects. Furthermore, several recent studies have demonstrated that, in addition
      to its being a potent antihistamine, levocetirizine has several anti-inflammatory
      effects that are observed at clinically relevant concentrations that may enhance
      its therapeutic benefit.

PMID- 17017923
TI  - Iodinated and gadolinium contrast media in computed tomography (CT) and magnetic
      resonance (MR) stroke imaging.
AB  - Thrombolysis has become an approved therapy for acute stroke. However, many
      stroke patients do not benefit from such treatment, since the presently used
      criteria are very restrictive, notably with respect to the accepted time window.
      Even so, a significant rate of intracranial hemorrhage still occurs. Conventional
      cerebral computed tomography (CT) without contrast has been proposed as a
      selection tool for acute stroke patients. Recently, more modern magnetic
      resonance imaging (MRI) and CT techniques, referred to as diffusion- and
      perfusion-weighted imaging, and perfusion-CT, have been introduced. They afford a
      comprehensive noninvasive survey of acute stroke patients as soon as their
      emergency admission, with accurate demonstration of the site of arterial
      occlusion and its hemodynamic and pathophysiological repercussions of the brain
      parenchyma. The objective of this review article is to present the advantages and
      drawbacks of CT, using iodinated contrast, and MRI, using gadolinium, in the
      evaluation of acute stroke patients.

PMID- 17017925
TI  - Drug hypersensitivity: epidemiology and risk factors.
AB  - Drug allergies are heterogeneous and multifactorial diseases and are always the
      consequence of an exaggerated immune-mediated reaction. Previously described
      models of immunologic mechanisms (mainly based on Gell and Combs' classification)
      cannot fully explain the physiopathology of these diseases; it seems therefore
      important to identify risk factors. Clinical and biologic tests are helpful
      diagnostic tools but are limited in their sensitivity and reliability and are
      certainly not predictive. Epidemiologic data supply information concerning the
      prevalence of drug hypersensitivity: female gender, concomitant infections (HIV,
      herpes) and concurrent illnesses (systemic lupus erythematosus) are all
      significant risk factors. Another host-related factor is the genetic
      predisposition of patients and is currently under investigation in our
      laboratory. Most genetic studies concern HLA haplotype association or
      polymorphism in genes encoding drug-metabolising enzymes. A current study by our
      group seems to implicate polymorphisms within the promoter of IL-10, a cytokine
      with anti-inflammatory properties. The chemical properties of the drug and the
      treatment regimen also influence the development of drug allergies.

PMID- 17017926
TI  - Hypersensitivity reactions to quinolones.
AB  - Quinolones are one of the most important classes of antimicrobial agents
      discovered in the recent years and one of the most widely used classes of
      antibiotics in clinical medicine. Their broad spectrum of activity and
      pharmacokinetic properties make them ideal agents for treating a variety of
      infections. Their clinical importance is further demonstrated by their activity
      against a wide range of diseases of public health importance such as anthrax,
      tuberculosis, bacterial pneumonia, and sexually transmitted diseases. Like other
      antibiotics, quinolones can cause various, sometimes dangerous hypersensitivity
      reactions. The underlying pathomechanisms are only poorly understood. Some are
      thought to be partly non-immune mediated reactions, others are considered to be
      IgE- or T cell-mediated reactions. This review gives an insight into the
      different immunological mechanisms leading to the diverse symptoms of quinolone
      induced hypersensitivity reactions, with special emphasis on the role of T cells
      in such reactions.

PMID- 17017927
TI  - Immediate hypersensitivity reactions to penicillins and other betalactams.
AB  - Immediate hypersensitivity reactions to betalactams are IgE mediated and
      constitute the most frequent allergic reactions mediated by specific
      immunological mechanisms. IgE responses to benzyl penicillin (BP), the first
      antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by
      a quick release of inflammatory mediators, resulting in anaphylactic shock,
      urticaria and angioedema. With the progressive appearance of other structures,
      comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE
      selective responses and cross-reactivity reactions were observed. The diagnosis
      of betalactam hypersensitivity, classically based on skin testing with major and
      minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has
      been modified by the inclusion of different determinants generated from these
      compounds, for which amoxicillin (AX) is the most relevant, followed by
      cephalosporins. Some subjects develop positive responses to several betalactams,
      mostly within the same family, but others develop a selective response. These are
      relevant for the appropriate selection of antimicrobial drugs in patients who
      have immediate hypersensitivity to betalactams.

PMID- 17017928
TI  - IgE-mediated hypersensitivity to cephalosporins.
AB  - Like penicillins, cephalosporins may cause IgE-mediated reactions such as
      urticaria, angioedema, and anaphylactic shock, which occur because of
      sensitization to determinants shared with penicillins or to unique cephalosporin
      haptens. In particular, side-chain structures may be responsible for selective
      sensitization or cross-reactivity. For this reason, individual free
      cephalosporins are usually employed in skin testing, in addition to the classic
      penicillin reagents. Cephalosporin skin tests are sensitive in diagnosing
      immediate hypersensitivity to these betalactams. As far as in vitro tests are
      concerned, IgE assays for cephalosporins, specifically sepharose
      radioimmunoassays, are a potentially useful tool in evaluating immediate
      reactions and could be used as complementary tests. In selected cases displaying
      negative results in both skin tests and IgE assays, a graded challenge with the
      implicated cephalosporin can be performed. Cephalosporin IgE-mediated
      hypersensitivity may be a transient condition; therefore, allergologic exams
      should be repeated in patients with negative initial allergologic work-ups,
      including challenges. Performing allergologic tests with cephalosporins other
      than the culprit, as well as with penicillin reagents, allows the identification
      of cross-reactivity with penicillins, selective responses, or cross-reactivity
      among cephalosporins. In the latter group, cross-reactivity is more frequently
      related to R1 than to R2 side-chain recognition. In assessing the selectivity of
      the response, negative results in skin testing with cephalosporins other than the
      responsible one appear to be a reliable indicator of tolerability.

PMID- 17017929
TI  - Hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs
      (NSAIDs).
AB  - Hypersensitivity to aspirin and other non steroidal anti-inflammatory drugs
      (NSAIDs) manifesting in the airways (rhinosinusitis, polyps, asthma) or in the
      skin (urticaria, angioedema) is the second most frequent untoward allergic
      reaction to drugs. Various aspects of this syndrome, such as its clinical
      features, the cell types and mediators involved, the role of underlying chronic
      inflammatory processes, the patterns of cross-reactivity between NSAIDs, the
      major role of sulfidoleukotrienes (LTC4) and of some other mediators such as
      prostaglandin E2 (PGE2) and C5a are briefly reviewed. It has been assumed for a
      long time that there were no reliable in vitro tests for that condition and that
      diagnostic confirmation can only be ascertained by provocation challenge. This
      appears no longer to be true, since several recent studies using a leukotriene
      release test (CAST) or a basophil activation test (BAT) on blood basophils, or a
      combination of both tests, yields positive results (70-75%) in a sizeable number
      of clinically validated cases, with a high specificity (above 85%). The finding
      in that syndrome of hyperreactive basophils suggests that the NSAID
      hypersensitivity syndrome is due to the associated effect of several factors: 1)
      Localized inflammatory processes causing a non specific cellular hyperreactivity;
      2) An abnormal pharmacogenetic reaction to NSAIDs resulting in a hyperproduction
      of LTC4 and other mediators by activated mast cells, basophils and eosinophils.

PMID- 17017930
TI  - Hypersensitivity reactions to iodinated contrast media.
AB  - Adverse reactions after iodinate contrast media (ICM) administration have been
      observed, which can be classified as immediate (i.e., occurring within one hour
      after administration) and delayed or non-immediate (i.e., occurring more than one
      hour after administration). Even though the incidence of ICM adverse reactions
      has been significantly reduced by the introduction of non-ionic compounds,
      immediate reactions still occur in about 3% of administrations. Different
      pathogenic mechanisms have been suggested for ICM reactions, including
      immunologic ones. Basophils and mast cells participate in immediate reactions
      through the release of mediators like histamine and tryptase, whereas a T-cell
      mediated pathogenic mechanism is involved in most non-immediate reactions,
      particularly maculopapular rashes. Skin tests and specific IgE assays are carried
      out to diagnose immediate hypersensitivity reactions, while both delayed-reading
      intradermal tests and patch tests are usually performed to evaluate non-immediate
      reactions. However, in vitro specific IgE assays are not commercially available.
      As far as in vitro tests are concerned, a response involving ICM-related T-cell
      activity may be assessed by the lymphocyte transformation test. Allergologic
      evaluation appears to be indicated in hypersensitivity reactions to ICM, although
      the sensitivity, specificity, and predictive values of allergologic tests have
      not yet been established. This paper summarizes the current state of the art and
      addresses the research that is still needed on the pathogenic mechanisms,
      diagnosis, and prevention of ICM-induced hypersensitivity reactions.

PMID- 17017931
TI  - Hypersensitivity to aromatic anticonvulsants: in vivo and in vitro cross
      reactivity studies.
AB  - Aromatic antiepileptic drugs (phenytoin, carbamazepine, oxcarbazepine, and
      phenobarbital) are frequently associated with cutaneous eruptions. A cell
      mediated pathogenic mechanism has been demonstrated in most of such reactions on
      the basis of positive responses to patch tests and/or lymphocyte transformation
      tests. Therefore, such tests are useful tools for evaluating anticonvulsant
      hypersensitivity reactions. Moreover, an in vitro lymphocyte toxicity assay,
      which exposes the patient's lymphocytes to arene oxides, has detected lymphocyte
      susceptibility to toxic metabolites in a large percentage of patients with
      hypersensitivity reactions to aromatic anticonvulsants. Although several
      hypersensitivity reactions to sequential exposure to more than one aromatic
      anticonvulsant (i.e., clinical cross-reactivity) have been reported, there are
      few studies performed with patch tests and/or lymphocyte transformation tests
      assessing immunologic cross-reactivity, and their data are contradictory. In any
      case, considering studies performed in samples of at least 10 patients, the
      immunologic cross-reactivity rate among aromatic anticonvulsants appears to be
      low. On the other hand, the reported rate of the toxic cross-reactivity (i.e.,
      assessed by lymphocyte toxicity assays) is high. Further in vivo and in vitro
      studies in large samples of subjects are needed to evaluate cross-reactivity
      among aromatic anticonvulsants.

PMID- 17017932
TI  - Cross-reactivity in cell-mediated and IgE-mediated hypersensitivity to
      glucocorticoids.
AB  - In the last few decades, glucocorticoids have received increasing attention for
      their capability of provoking systemic hypersensitivity reactions, when
      administered orally, parenterally, or intralesionally, as well as allergic skin
      and mucosal symptoms, when applied locally to the skin in patients with contact
      dermatitis or to the mucosa in patients with asthma and/or rhinitis. However,
      because of their anti-inflammatory and immunosuppressive properties,
      glucocorticoids are often not suspected of such hypersensitivity reactions. In
      addition, because glucocorticoids retain their anti-inflammatory potential, even
      if they act as sensitizers, the signs and symptoms of allergic reactions are not
      always obvious, particularly when they overlap with those caused by the very
      diseases glucocorticoids are used to treat. Moreover, interpretation of
      diagnostic tests, specifically that of patch-test reactions, can be difficult. In
      this review, particular attention is addressed to the problem of allergenic cross
      reactivity among topical and systemic glucocorticoids. We also look at the
      clinical and practical aspects of both cell-mediated and IgE-mediated
      hypersensitivity reactions to glucocorticoids and their consequences on anti
      inflammatory therapeutic choices.

PMID- 17017933
TI  - Hypersensitivity reactions to complementary and alternative medicine products.
AB  - Complementary and alternative medicine (CAM) is becoming increasingly popular,
      and is often used for treating hypersensitivity diseases. Virtually all
      alternative remedies can cause hypersensitivity reactions, but the most
      frequently involved ones are tea tree oil, members of the Compositae family,
      propolis, oils used in aromatherapy, substances responsible for
      photosensitization, and metal-containing compounds. The main target organ is
      skin, with manifestations ranging from contact dermatitis (the most common) to
      urticaria-angioedema, maculopapular eruptions, photosensitivity reactions, and
      the Stevens-Johnson syndrome. Other types of reactions are possible, including
      respiratory and anaphylactic ones. Different pathogenic mechanisms have been
      suggested for CAM product reactions, including immunologic ones. Basophils and
      mast cells participate in IgE-mediated reactions through the release of mediators
      like histamine and tryptase, whereas a T-cell-mediated pathogenic mechanism is
      involved in most delayed reactions, particularly contact dermatitis and
      maculopapular eruptions. Skin tests and serum specific IgE assays are carried out
      to diagnose immediate hypersensitivity reactions, while patch tests and
      lymphocyte transformation tests are usually performed to evaluate delayed
      hypersensitivity reactions. Thus clinicians should know about the potential of
      CAM products for causing adverse reactions. Our study is aimed at highlighting
      the risk of hypersensitive reactions to CAM remedies on the basis of the numerous
      cases reported in the literature. Because little is known about adverse reactions
      to CAM products, further systematic studies and an appropriate regulation by
      heath authorities are necessary.

PMID- 17017934
TI  - Hypersensitivity reactions to ophthalmic products.
AB  - Adverse reactions after administration of ophthalmic products have frequently
      been observed. These reactions can be provoked by both active principles and
      excipients. Different pathogenic mechanisms have been suggested for such
      reactions, including immunologic ones. Basophils and mast cells participate in
      IgE-mediated reactions through the release of mediators like histamine and
      tryptase, whereas a T-cell-mediated pathogenic mechanism is involved in most
      delayed reactions, particularly conjunctival ones and eyelid dermatitis. Prick
      tests and immediate-reading intradermal tests are carried out to diagnose
      immediate hypersensitivity reactions, while patch tests are usually performed to
      evaluate delayed reactions. Other diagnostic tests, such as serum-specific IgE
      assays in immediate reactions, as well as delayed-reading intradermal tests
      and/or lymphocyte transformation tests in delayed ones, are rarely performed. In
      this review, particular attention is addressed to the clinical and practical
      aspects of both cell-mediated and IgE-mediated hypersensitivity reactions to
      ophthalmic products.

PMID- 17017935
TI  - Dehydroepiandrosterone and its derivatives: potentially novel anti-proliferative
      and chemopreventive agents.
AB  - Dehydroepiandrosterone (DHEA) is the most abundant adrenal androgenic steroid in
      young adult humans. The physiological functions of DHEA in preventing human
      carcinogenesis are still controversial, but a lot of reports have shown that
      pharmacological doses of DHEA show chemopreventive and anti-proliferative effects
      on tumors in rodents. Although a therapeutic dose of DHEA has been reported to
      promote hepatocarcinogenesis in rats due to peroxisomal proliferation, it remains
      unclear whether DHEA is a peroxisome proliferator in human liver. The
      chemopreventive and anti-proliferative effects of DHEA are not explained by a
      single mechanism, and at least four mechanisms seem to contribute to these
      effects: 1) depletion of NADPH and ribose-5-phosphate due to the inhibition of
      glucose-6-phosphate dehydrogenase activity, 2) suppression of cholesterol
      biosynthetic pathway by inhibition of HMG-CoA reductase, 3) interference with
      cell proliferation signaling pathways, and 4) suppression of nitric oxide
      generation through down-regulation of nitric oxide synthase II. In addition to
      studies of the mechanisms underlying the anti-neoplastic effects, searches for
      more potent and less androgenic DHEA derivatives are ongoing. A small amount of
      DHEA is endogenously metabolized to 7-oxygenated DHEA, and this may represent a
      metabolic pathway to more potent steroid hormones. Androsterone, epiandrosterone
      and etiocholanolone have been considered to be merely inactive end products of
      DHEA, but may in fact be physiological effectors in their own right. In addition,
      DHEA analogs such as 3beta-methyl-5-androsten-17-one, 16alpha-fluoro-5-androsten
      17-one and 16alpha-fluoro-5alpha-androstan-17-one have been synthesized and shown
      to be more effective inhibitors of tumor growth, compared with DHEA itself.
      However, to design potent and safe DHEA derivatives, identification of the DHEA
      receptor and clarification of the mechanisms of DHEA action are required.

PMID- 17017936
TI  - Kinins and cardiovascular diseases.
AB  - Kinins are synthesized from their precursors by different enzymes and participate
      in the regulation of cardiovascular function through bradykinin (BK) B1 and B2
      receptors. They modulate blood coagulation by exerting antithrombotic and
      profibrinolytic actions. By activating B2 receptors that results in the release
      of nitric oxide and prostacyclin, kinins inhibit vascular smooth muscle growth
      and neointima formation, which may play an inhibitory role on the atherosclerosis
      development, while through the activation of B1 receptors, they may play a
      deleterious role in this disease. Kinins are potent endogenous vasodilators that
      are involved in the regulation of coronary vascular tone. However, due to their
      metabolic characteristics, these peptides act mainly as an autocrine/paracrine
      factor to locally regulate blood perfusion of organs. By modulating cellular
      energy metabolism and myocardial oxygen consumption, they protect cardiac and
      vascular endothelial function in myocardial ischemia and heart failure. Finally,
      mounting evidence indicates that kinins are involved in the actions of some drugs
      actually used in the treatment of cardiovascular diseases such as angiotensin
      converting enzyme inhibitors and angiotensin AT1 receptor antagonists. Taken
      together, the kinin system constitutes a potential therapeutic target for
      cardiovascular diseases. Experiments in animals attempted to explore the kinin
      system as a therapeutic means, including the mobilization of endogenous kinins
      using pharmacological agents, searching BK analogs with long-acting properties
      and gene therapies. However, the potential values of the kinin system have not
      been taken into consideration in clinical practice for cardiovascular
      indications.

PMID- 17017938
TI  - Expression, distribution and regulation of phosphodiesterase 5.
AB  - Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian
      phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP)
      and cyclic adenosine monophosphate (cAMP). Best known as the target of the
      impotence drug sildenafil, PDE5 degrades cGMP in smooth muscle cells so as to
      maintain the contracted state of contractile organs such as the penis, blood
      vessels, uterus, and intestines. In addition, it regulates numerous other
      physiological processes such as neurogenesis and apoptosis. Like all other PDEs,
      PDE5 is dimeric; each subunit is approximately 100 kd in size and has two
      allosteric cGMP-binding sites and a catalytic domain. Protein kinase G (PKG)
      mediated phosphorylation and allosteric cGMP binding upregulate PDE5 activity,
      while PP1 phosphatase-mediated dephosphorylation downregulates. Sildenafil and
      other selective inhibitors inhibit PDE5 by binding to the catalytic site. From
      two promoters a single PDE5A gene at human chromosome 4q26 encodes three
      alternatively spliced isoforms (PDE5A1-3) that differ in the N-terminus. The
      PDE5A promoter is located upstream of the three isoform-specific first exons (in
      the order of A1-A3-A2) and consists of a 139-bp core, a 308-bp upstream enhancer,
      and a 156-bp downstream enhancer. The weaker 182-bp PDE5A2 promoter is located
      between the A3- and A2-specific exons and contains an indispensable Sp1-binding
      sequence. Both promoters are responsive to cGMP or cAMP stimulation, and several
      studies have demonstrated regulation of PDE5 expression possibly through these
      promoters. Virtually all tissues and cell types express PDE5, with heart and
      cardiomyocytes being contentious. PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is
      specific to smooth muscle.

PMID- 17017939
TI  - Phosphodiesterase 5 inhibitors--drug design and differentiation based on
      selectivity, pharmacokinetic and efficacy profiles.
AB  - The discovery that inhibition of phosphodiesterase-5 (PDE5) reduces the
      degradation of cGMP, allowing erectile function to occur by relaxation of penile
      smooth muscle, represents a revolutionary approach or the treatment of erectile
      dysfunction (ED). Three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil)
      are clinically available at this time, and extensive drug design efforts are
      registered for finding agents with a better activity, enhanced selectivity and
      reduced side effects. Many classes of such compounds have been reported,
      belonging to diverse chemical entities. The drug design has been very much
      facilitated after the report of the X-ray crystal structure of the PDE5 catalytic
      domain in complex with the three clinically used derivatives. PDE5 inhibitor
      therapy, has been found to be effective in special clinical populations, such as
      those with prostate cancer, diabetes, and cardiovascular disease. The duration of
      action of sildenafil and vardenafil is of about 4 hours, whereas that of
      tadalafil is of about 36 hours, and the overall safety of the treatments is good.
      There is a risk of hypotension if nitrates are given concurrently with the PDE5
      inhibitors. Common side-effects include headache, facial flushing, nasal
      congestion, dyspepsia and transient visual impairment. There are pharmacological
      interactions between these drugs and other medications metabolized by the
      cytochrome P450 (P3A4 isoform), such as the azole antifungals, erythromycin and
      the HIV protease inhibitors.

PMID- 17017940
TI  - Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction.
AB  - Erectile dysfunction (ED) has multifactor pathogenesis, with neurological,
      vascular, endocrinological and psychogenic components described. However, about
      50-85% of ED population report the presence of one or more comorbidities i.e.
      hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair
      endothelial function and, erection is a basically vascular event that
      necessitates an intact endothelium to occur. Hence, ED may be mostly considered
      as the clinical manifestation of a disease affecting penile circulation as a part
      of a generalized vascular disorder due to atherosclerosis. Orally active drugs,
      i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of on-demand drugs
      licensed for ED treatment and appear to offer advantages over past therapies in
      terms of ease of administration and cost, and they are now widely advocated as
      first-line therapy. The recent discovery that chronic not on-demand
      administration of these drugs may improve erectile and endothelial response in
      men previously unresponding to on-demand regimes, opens a new scenario in the
      treatment of men with ED and comorbidities. Finally, the recent approval of PDE5
      i sildenafil for the treatment of pulmonary arterial hypertension represents the
      new challenge for these class of drugs. Aim of this article will be to provide an
      update on the pathophysiology of ED and how to use of different available PDE5-i
      in approaching sexual dysfunctional men, pointing out on their characteristic of
      efficacy and safety and different indications in special sub-populations.

PMID- 17017941
TI  - Cardiovascular effects of phosphodiesterase 5 inhibitors.
AB  - Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are
      now approved for the treatment of erectile dysfunction. They inhibit the cGMP
      specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which,
      for example in smooth muscle cells, reduces muscular tone. In the cardiovascular
      system, they slightly reduce arterial systemic blood pressure. This moderate
      effect was also shown in combination with many antihypertensive drugs. But the
      important contraindication is the concomitant use of PDE 5 inhibitors with any
      drug serving as a nitric oxide donor, as this combination can lead to significant
      arterial hypotension. Caution is needed in patients on alpha-blocking agents. In
      general, this class of drugs was not shown to exhibit direct deleterious effects
      on the myocardium or promote arrhythmias. Furthermore, statistical evaluations
      did not demonstrate an increased risk for patients taking PDE 5 inhibitors in
      comparison with an adequate control population. Many patients suffering from
      erectile dysfunction may be characterized by multiple cardiovascular risk factors
      or even ischemic heart disease, suggesting an increased baseline risk. While in
      many forms of erectile dysfunction, these agents seem to be very effective, it
      becomes clear that endothelial dysfunction is an attractive target of PDE 5
      inhibitors and may also be the underlying cause in many types of erectile
      dysfunction. In addition, these agents seem to be very effective in lowering
      pulmonary arterial pressure, which might provide the opportunity to treat primary
      and some forms of secondary pulmonary hypertension, perhaps in combination with
      inhaled nitric oxide or other pulmonary arterial vasodilators. Sildenafil was
      approved for treatment of primary arterial hypertension in the U.S. in June 2005.
      Recently, direct cardioprotective effects were described in animal research,
      resembling preconditioning-like effects, which may, under certain conditions,
      also be applicable in clinical research.

PMID- 17017943
TI  - Signal transduction pathways of inflammatory gene expressions and therapeutic
      implications.
AB  - Intercellular adhesion molecule-1 (ICAM-1), an inducible cell adhesion
      glycoprotein of the immunoglobulin supergene family and cyclooxygenase-2 (COX-2),
      an inducible prostaglandin G/H synthase, are overexpressed by proinflammatory
      mediators in a wide variety of cell types. These stimuli increase ICAM-1 or COX-2
      expression primarily through activation of ICAM-1 or COX-2 gene transcription.
      The architecture of the ICAM-1 or COX-2 promoter is complex, containing a large
      number of binding site for inducible transcription factors, the most important of
      which is NF-kB. NF-kB acts in concert with other transcription factors or
      transcriptional coactivators which facilitate the assembly of distinct
      stereospecific transcription complexes on the ICAM-1 or COX-2 promoter. These
      transcription complexes presumably mediate the induction of ICAM-1 or COX-2
      expression in different cell types and in response to different stimuli. In this
      review, I summarize the current understanding of ICAM-1 and COX-2 gene regulation
      with a particular emphasis on the transcription factors or coactivators, and
      signal transduction pathways critical for their expression. A PKC-dependent c-Src
      pathway activating NF-kB or GAS to enhance ICAM-1 or COX-2 gene expression is
      discussed. Furthermore, natural products and novel agents targeting on the
      transcription factor with potential anti-inflammation and anti-tumor activity are
      also discussed.

PMID- 17017944
TI  - Anti-inflammatory drugs in the treatment of neurodegenerative diseases: current
      state.
AB  - Increasing evidence indicates that inflammation is involved in the pathogenesis
      of many neurological, particularly neurodegenerative diseases. Even if
      inflammation is not a primary causative process, its presence may contribute to
      the continued loss of CNS neurons. Therefore, it seems reasonable to propose that
      use of anti-inflammatory drugs might diminish the cumulative effects of
      inflammation in the brain. Indeed, some epidemiological studies performed to
      date, especially in Alzheimer's disease, suggests that sustained use of anti
      inflammatory drugs (AIDs) may prevent or slow down the progression of
      neurodegenerative diseases. However, small number of clinical trials carried out
      so far using AIDs, were minimal and equivocal in their outcome. Potential reasons
      for these mixed results include timing of AIDs administration, nonselective
      inhibition of cyclooxygenase (COX), inappropriate use of particular anti
      inflammatory drugs for a given disease or disease progression/ severity, sub
      optimal dose in target site, or limited penetration to the brain through the
      blood-brain barrier (BBB). Therefore, design of AIDs for the treatment of
      neurodegenerative diseases based upon better BBB penetration, and with minimal
      adverse events, would be appropriate. In addition, relevant genetic differences
      among patients should be considered planning new AIDs, for improved efficacy.
      Furthermore, due to the possible co-involvement of oxidative stress and
      excitotoxicity in the pathogenesis of these diseases, combination therapy with
      antioxidants or glutamate antagonists or a multi-potent drug might be much more
      effective in successfully treating neurodegenerative diseases.

PMID- 17017945
TI  - Dual effects of antioxidants in neurodegeneration: direct neuroprotection against
      oxidative stress and indirect protection via suppression of glia-mediated
      inflammation.
AB  - Oxidative stress, in which production of highly reactive oxygen species (ROS) and
      reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of
      many neurological diseases and neurodegeneration. ROS and RNS generated
      extracellularly and intracellularly by various processes initiate and promote
      neurodegeneration in CNS. ROS and RNS can directly oxidize and damage
      macromolecules such as DNA, proteins, and lipids, culminating in
      neurodegeneration in the CNS. Neurons are most susceptible to direct oxidative
      injury by ROS and RNS. ROS and RNS can also indirectly contribute to tissue
      damage by activating a number of cellular pathways resulting in the expression of
      stress-sensitive genes and proteins to cause oxidative injury. Moreover,
      oxidative stress also activates mechanisms that result in a glia-mediated
      inflammation that also causes secondary neuronal damage. Associated with neuronal
      injuries caused by many CNS insults is an activation of glial cells (particularly
      astrocytes and microglia) at the sites of injury. Activated glial cells are thus
      histopathological hallmarks of neurodegenerative diseases. Even though direct
      contact of activated glia with neurons per se may not necessarily be toxic, the
      immune mediators (e.g. nitric oxide and reactive oxygen species, pro-inflammatory
      cytokines and chemokines) released by activated glial cells are currently
      considered to be candidate neurotoxins. Therefore, study of the protective role
      of antioxidant compounds on inhibition of the inflammatory response and
      correcting the fundamental oxidant/antioxidant imbalance in patients suffering
      from neurodegenerative diseases are important vistas for further research. The
      purpose of this review is to summarize the current evidence in support of this
      critical role played by oxidative stress of neuronal and glial origin in
      neurodegenerative diseases. The mechanistic basis of the neuroprotective activity
      of antioxidants does not only rely on the general free radical trapping or
      antioxidant activity per se in neurons, but also the suppression of genes induced
      by pro-inflammatory cytokines and other mediators released by glial cells. We
      propose that combinations of agents which act at sequential steps in the
      neurodegenerative process can produce additive neuroprotective effects. A
      cocktail of multiple antioxidants with anti-inflammatory agents may be more
      beneficial in the prevention of neurodegenerative disease. A clearer appreciation
      of the potential therapeutic utility of antioxidants would emerge only when the
      complexity of their effects on mechanisms that interact to determine the extent
      of oxidative damage in vivo are more fully defined and understood.

PMID- 17017946
TI  - Possible therapies of septic shock: based on animal studies and clinical trials.
AB  - The intention of this review is to give a brief overview of the continuously
      expanding field of sepsis therapy based on recent studies with animal models and
      clinical trials. Over the past few years, it has become apparent that the
      mechanisms controlling this disease are more complex than was previously thought,
      with factors such as free radicals, nuclear factors, and enzyme co-factors all
      contributing in the control of the pathogenesis of sepsis as well and
      improvements in the morbidity. Recent advances at the molecular biology level
      have facilitated the development of a whole new field of research. In addition, a
      number of groups have also shown that free radicals can modulate the expression
      of several genes. Probably an effect that is due to an interaction between free
      radicals and transcription factors. Further elucidation of the signals that
      influence the production and actions of free radicals will, without doubt,
      further our understanding of the numerous pathophysiological processes involved
      in sepsis. For these reasons, there is considerable interest in alternative
      treatment modalities which focus on recent animal studies. These recent
      experimental approaches to the therapy of sepsis are discussed in light of each
      step in the complex inflammatory cascade involved and compared to traditional
      approaches to the prevention and therapy of sepsis and septic shock.

PMID- 17017947
TI  - Therapeutic use of nitric oxide scavengers in shock and sepsis.
AB  - Nitric oxide (NO) is a reactive radical produced by the enzyme nitric oxide
      synthase (NOS) and it plays an important role in a large number of biological
      pathways. NO can be produced under normal physiologic conditions and contribute
      to homeostasis but, when produced in excess, it may lead to tissue injury and
      organ dysfunction. The regulation of NOS activity and expression is becoming
      increasingly understood. NOS enzyme inhibitors as tools to decrease excessive NO
      synthesis have received the most attention and have been subjected to the
      greatest experimental study. Compounds that scavenge excessive NO have been
      developed and have shown promise in a number of experimental models but have
      received considerably less attention as potential therapeutic agents. In this
      article, the use of NO scavengers in two conditions in which excessive NO appears
      to be pathophysiologically significant, shock and sepsis, is reviewed. The
      relevant biology of NO in these disease states is presented and the therapeutic
      potential of NO scavengers in clinical care is explored.

PMID- 17017948
TI  - Role of nitric oxide and reactive oxygen species in arthritis.
AB  - A vast amount of circumstantial evidence implicates oxygen-derived free radicals,
      especially reactive oxygen species and nitric oxide as mediators of inflammation
      and/or tissue destruction in inflammatory and arthritic disorders. The aim of the
      current article is to overview the recent developments in this field, as it
      relates to the roles of nitric oxide (NO) and reactive oxygen species in the
      pathogenesis of this condition. The first part of the review focuses on the
      biochemical impact of NO and reactive oxygen species. The second part of the
      review deals with the novel findings related to the recently identified
      regulatory roles of the inducible isoform of nitric oxide synthase (iNOS) in the
      expression of pro-inflammatory mediators in inflammation. Reactive oxygen species
      can initiate a wide range of toxic oxidative reactions. These include initiation
      of lipid peroxidation, direct inhibition of mitochondrial respiratory chain
      enzymes, inactivation of glyceraldehyde-3phosphate dehydrogenase, inhibition of
      membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium
      channels, and other oxidative modifications of proteins. All these toxicities are
      likely to play a role in the pathophysiology of inflammation. Reactive oxygen
      species are all potential reactants capable of initiating DNA single strand
      breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose)
      synthetase (PARS), leading to eventual severe energy depletion of the cells, and
      necrotic-type cell death. Recently it has been demonstrated that iNOS inhibitor
      prevents the activation of poly (ADP ribose) synthetase, and prevents the organ
      injury associated with inflammation. Although the severity and duration of
      inflammation may dictate the timing and extent of NOS expression, it is now
      evident that the up-regulation of NOS can take place during sustained
      inflammation. Thus, induced nitric oxide, in addition to being a "final common
      mediator" of inflammation, is essential for the up-regulation of the inflammatory
      response. Furthermore, a picture of a pathway is evolving that contributes to
      tissue damage both directly via the formation of reactive oxygen species, with
      them associated toxicities, and indirectly through the amplification of the
      inflammatory response.

PMID- 17017951
TI  - Monoclonal antibodies in the management of solid tumors.
AB  - Thorough understanding of the complex interactions between components of
      immunological response has led to the arousal of the concept of immune-mediated
      anti-cancer therapy. Although, the use of monoclonal antibodies (MAbs) in
      hematological malignancies met with success, therapy of solid tumors has been
      impeded by many obstacles. Some MAbs have increased the efficacy of treatment of
      certain tumors with acceptable adverse events. Trastuzumab, cetuximab and
      bevacizumab have become FDA approved for the treatment of breast and colorectal
      cancer, respectively. The dosing strategies, timing and schedule of antibody
      administration, duration of treatment are yet to be determined under specific
      circumstances. Combinations with other biologic agents, such as small-molecule
      inhibitors of the same pathway would be really useful. Multimodality approaches
      are based on synergistic effects observed with the combination of antibodies with
      chemotherapeutic drugs and/or radiotherapy. Immune-mediated effects may be
      further exploited with the use of bivalent (bispecific) molecules, while
      radioimmunotherapy via radiolabelling of the antibody is feasible. Modified
      recombinant antibodies could be applied for toxin delivery to tumor cells, while
      molecules fused with drug-activating enzymes can mediate prodrug therapy.
      Increased penetrability into tumors can also be achieved with novel antibody
      fragments. In the future, better selection of patient subpopulations with tumors
      overexpressing disease-related clinical biomarkers could result in an increase in
      both efficacy and specificity of antibody-based treatment.

PMID- 17017950
TI  - Immunotherapeutic and immunoregulatory drugs in haematologic malignancies.
AB  - A better understanding of the biology and pathogenesis of hematological
      malignancies has led to the development of immunotherapeutic and immunoregulatory
      drugs. Many of these agents have revolutionized the current treatment modalities,
      while others are under investigation. Rituximab (anti-CD20 antibody) has been
      established as the gold standard of treatment for aggressive B-cell lymphomas in
      combination with CHOP and has shown significant activity as monotherapy in the
      treatment of indolent B-cell lymphomas. In follicular lymphomas the combination
      of Rituximab with chemotherapy improves the outcome compared to chemotherapy
      alone. CD 20-based radioimmunotherapy, with the advantage of the bystander
      effect, represents an additional therapeutic alternative in B-cell lymphomas and
      may produce tumor regression in Rituximab resistant patients. The anti-CD52
      monoclonal antibody, alemtuzumab, further expands the armamentarium against
      lymphoid malignancies producing high response rates in these entities. Antibody
      targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33
      antibody combined to calicheamicin, has shown efficacy in the treatment of
      refractory acute myeloid leukemia; exact indications, timing and dosing schedule
      for optimized efficacy remain to be determined. Interferons have proven
      significant activity in cutaneous lymphomas, hairy cell leukemia and chronic
      myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by
      acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic
      cells microenvironment and lead to disease control in multiple myeloma as well as
      in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor,
      displays significant anti-tumor activity, especially in multiple myeloma and
      lymphoproliferative disorders. The addition of these agents in therapeutic
      regimens has improved considerably the treatment of hematological malignancies.

PMID- 17017952
TI  - Anti-TNF-alpha antibody therapies in autoimmune diseases.
AB  - Autoimmune diseases affect about 3% of the world population, more frequently
      women than men, and their incidence is attributed to an immune response of a
      genetically predisposed individual to an environmental pathogen, under the
      influence of inadequate immuno-regulatory mechanisms. Advances in understanding
      the cellular activity pathways and cytokine expression profiles have led to new
      therapeutic regiments, like soluble receptors, monoclonal antibodies and
      molecular mimetics that have been employed to enhance or replace conventional
      immunosuppressive therapies. Among new biologicals that have been developed to
      target defined pathways of the adaptive immune response are TNF-alpha inhibitors.
      TNF-alpha is a proinflammatory cytokine elevated in many autoimmune lesions, and
      its deregulation characterizes many autoimmune diseases. TNF-alpha seems to
      exhibit an immunoregulatory role that can alter the balance of T regulatory cells
      and orchestrate acute immunological responses. More than half a million
      autoimmune patients have received therapy with anti-TNF-alpha antibodies, usually
      because they were refractory to conventional treatments. This review offers an
      update on TNF-alpha-targeted therapies used in patients suffering from various
      autoimmune diseases, based on the current knowledge of disease pathogenesis, with
      emphasis on the efficacy and safety that clinical trials have shown until now.

PMID- 17017953
TI  - Artificial carriers: a strategy for constructing antigenic/immunogenic
      conjugates.
AB  - The rational design of artificial carriers for anchoring multiple copies of B
      and/or T cell epitopes, built-in vaccine adjuvants and "promiscuous" T cell
      epitopes for the construction of conjugates as antigenic substrates or potent
      immunogens has been the stimulus of intensive efforts nowadays. The unambiguous
      composition, the reliability and the versatility of the production of
      reconstituted antigens or immunogens has found a great number of biochemical
      applications in developing immunoassays of high sensitivity, specificity and
      reproducibility and in generating site-specific antibodies for usage as human
      vaccine candidates. In this review are summarized different types of artificial
      carriers currently used as dendrimers bearing branching segments, multimeric core
      matrices and templates with built-in folding devices. Emphasis is given to the
      construction and application of a helicoid-type Sequential Oligopeptide Carrier
      (SOCn) developed in our laboratory. The beneficial structural elements of SOCn
      induce a favorable arrangement of the conjugated peptides, which also retain
      their initial "active" conformation, so that potent antigens and immunogens are
      generated.

PMID- 17017954
TI  - RNA-mediated therapeutics: from gene inactivation to clinical application.
AB  - The specific targeting and inactivation of gene expression represents nowadays
      the goal of the mainstream basic and applied biomedical research. Both
      researchers and pharmaceutical companies, taking advantage of the vast amount of
      genomic data, have been focusing on effective endogenous mechanisms of the cell
      that can be used against abnormal gene expression. In this context, RNA
      represents a key molecule that serves both as tool and target for deploying
      molecular strategies based on the suppression of genes of interest. The main RNA
      mediated therapeutic methodologies, deriving from studies on catalytic activity
      of ribozymes, blockage of mRNA translation and the recently identified RNA
      interference, will be discussed in an effort to understand the utilities of RNA
      as a central molecule during gene expression.

PMID- 17017955
TI  - Regulatory T-cells: immunomodulators in health and disease.
AB  - Regulation of immune responses is crucial in order to maintain immunological self
      tolerance. This is maintained in the periphery by a number of cell types that
      have the capacity to control and regulate immune responses, thus preventing
      reactivity to self while monitoring appropriate, non-exuberant responses to non
      self-antigens. The various mechanisms of regulation will be discussed in this
      review together with how this knowledge could be used to develop better drugs and
      treatments for various diseases.

PMID- 17017956
TI  - Immunosuppressive drugs in HIV disease.
AB  - Hyper activation of the immune system has emerged as an important clinical marker
      of HIV disease progression to AIDS. During the chronic phase of the disease,
      chronic immune activation is linked to systemic CD4 T-cell depletion and eventual
      immune failure. Additionally, the HIV virus per se seems to engage in a form of
      molecular parasitism for host T-cell signaling pathways and transcription factors
      (e.g. NFAT). Targeting host T-cell factors that mediate immune activation in
      conjunction with HAART (Highly Active Antiretroviral Therapy) could be the basis
      of novel immune-modulatory regimens that avoid the development of mutant viral
      strains. Hence the three-signal model of T-cell activation provides a framework
      for the rational selection of immunomodulatory therapies in HIV disease. Within
      this framework we examine the immunosuppressive, and antiretroviral properties of
      NFAT (calcineurin) inhibitors (cyclosporine and tacrolimus), the purine rescue
      pathway inhibitor mycophenolate mofetil and sirolimus (rapamycin). The results of
      small clinical studies to date are reviewed and they suggest that
      immunosuppressive medications might be a safe and effective adjunct to HAART in
      stable HIV disease, when such medications are used in full doses. Finally, we
      discuss the potential implications of such therapies for solid organ
      transplantation in HIV patients.

PMID- 17017957
TI  - Rethinking target discovery in polygenic diseases.
AB  - Despite an extraordinary investment in R&D the yield of successful new drugs has
      been disproportionately low in recent years, suggesting that the whole process of
      drug development requires rethinking and reform. Most analyses on this issue
      focus on molecular target discovery considerations. Target identification is
      characterized by a surplus of potential targets, but there is a translational
      bottleneck primarily due to limitations of currently employed target validation
      platforms. Meanwhile, the clinical entities, to which treatments are directed,
      are also highly complex in terms of pathophysiologic mechanisms and
      manifestations. In the present study we discuss the limitations of current
      molecular target discovery approaches mainly in regard to selectivity and
      efficacy. We also describe the constraints imposed on drug development by the
      current diagnostic constructs and the tendency towards dissecting the complex
      clinical phenotypes to component intermediate phenotypes. Finally, we describe
      how the reconsideration of molecular and clinical targets in polygenic diseases
      may lead to new strategies of pharmacological intervention directed against
      component dysfunctions, rather than the whole complex phenotype. Such strategies
      involve the combination of single ligands that act selectively on multiple
      molecules involved in a particular disease, or the employment of "multi-targeted"
      drugs, i.e. single drug molecules that hit selectively multiple receptors sharing
      common binding sites.

PMID- 17017959
TI  - Serotonin reuptake inhibitors: the corner stone in treatment of depression for
      half a century--a medicinal chemistry survey.
AB  - Inhibition of serotonin (5-HT) reuptake has been a central theme in the therapy
      of depression for half a century. Through the years these therapies have
      improved, particularly with regard to side effects, and today's selective
      serotonin reuptake inhibitors (SSRIs) constitute a reasonably effective offer for
      the patients. However, there is still room for major improvement and considering
      that almost 20% of the population in the western world will experience a
      depressive period in their lifetime, there is a large need for improved
      therapies. A large spectrum of targets and strategies are currently being
      pursued, but so far none of these new approaches have been successful, mainly due
      to lack of a deeper understanding of the disease biology. Since inhibition of 5
      HT reuptake ensures a certain degree of antidepressant efficacy, there has been a
      large interest in various combinations with serotonin reuptake inhibitors (SRIs)
      in order to improve on the shortcomings of treatment with SSRIs. Some of these
      approaches have resulted in marketed antidepressants, eg combinations of SRI with
      norepinephrine (NE) reuptake inhibition, whereas other approaches are still at an
      experimental stage. This review attempts to present the current status of these
      add-on/combination approaches with particular focus on the medicinal chemistry
      aspects.

PMID- 17017960
TI  - Dopamine transporter ligands: recent developments and therapeutic potential.
AB  - The dopamine transporter (DAT) is a target for the development of
      pharmacotherapies for a number of central disorders including Parkinson's
      disease, Alzheimer's disease, schizophrenia, Tourette's syndrome, Lesch-Nyhan
      disease, attention deficit hyperactivity disorder (ADHD), obesity, depression,
      and stimulant abuse as well as normal aging. Considerable effort continues to be
      devoted to the development of new ligands for the DAT. In this review, we present
      some of the more interesting ligands developed during the last few years from the
      3-phenytropane, 1,4-dialkylpiperazine, phenylpiperidine, and benztropine classes
      of DAT uptake inhibitors as well as a few less studied miscellaneous DAT uptake
      inhibitors. Studies related to the therapeutic potential of some of the more
      studied compounds are presented. A few of the compounds have been studied as
      pharmacotherapies for Parkinson's disease, ADHD, and obesity. However, most of
      the drug discovery studies have been directed toward pharmacotherapies for
      stimulant abuse (mainly cocaine). A number of the compounds showed decreased
      cocaine maintained responding in rhesus monkeys trained to self-administer
      cocaine. One compound, GBR 12,909, was evaluated in a Phase 1 clinical trial.

PMID- 17017961
TI  - Therapeutic potential of monoamine transporter substrates.
AB  - Monoamine transporter proteins are targets for many psychoactive compounds,
      including therapeutic and abused stimulant drugs. This paper reviews recent work
      from our laboratory investigating the interaction of stimulants with transporters
      in brain tissue. We illustrate how determining the precise mechanism of stimulant
      drug action (uptake inhibitor vs. substrate) can provide unique opportunities for
      medication discovery. An important lesson learned from this work is that drugs
      which display equipotent substrate activity at dopamine (DA) and serotonin (5-HT)
      transporters have minimal abuse liability and few stimulant side-effects, yet are
      able to suppress ongoing drug-seeking behavior. As a specific example, we
      describe the development of PAL-287 (alpha-methylnapthylethylamine), a dual DA/5
      HT releasing agent that suppresses cocaine self-administration in rhesus monkeys,
      without the adverse effects associated with older phenylethylamine 5-HT releasers
      (e.g., fenfluramine) and DA releasers (e.g., amphetamine). Our findings
      demonstrate the feasibility of developing non-amphetamine releasing agents as
      potential treatments for substance abuse disorders and other psychiatric
      conditions.

PMID- 17017962
TI  - Structure-activity relationships of selective GABA uptake inhibitors.
AB  - For more than four decades there has been a search for selective inhibitors of
      GABA transporters. This has led to potent and selective inhibitors of the cloned
      GABA transporter subtype GAT1, which is responsible for a majority of neuronal
      GABA transport. The only clinically approved compound with this mechanism of
      action is Tiagabine. Other GABA transporter subtypes have not been targeted with
      comparable selectivity and potency. We here review a comprehensive series of
      competitive inhibitors that provide information about the GABA recognition site
      and summarise the structure-activity relations in a ligand-based pharmacophore
      model that suggests how future compounds could be designed. Finally, some of the
      recent results on subtype-characterised competitive inhibitors and recent
      lipophilic aromatic GABA uptake inhibitors are reviewed.

PMID- 17017963
TI  - Progress in the preparation and testing of glycine transporter type-1 (GlyT1)
      inhibitors.
AB  - Clinically utilized antipsychotic agents share as a common mechanism the ability
      to antagonize dopamine D2 receptors and it is widely assumed that this activity
      contributes to their efficacy against the positive symptoms of schizophrenia. The
      efficacy of currently marketed antipsychotic agents on the negative and cognitive
      symptoms of this disease, however, is not optimal. One alternate hypothesis to
      the "dopamine hypothesis" of schizophrenia derives from the observation that
      antagonists of NMDA receptor activity better mimic the symptomatology of
      schizophrenia in its entirety than do dopamine agonists. Findings from this line
      of research have led to the NMDA receptor hypofunction (or glutamate dysfunction)
      hypothesis of schizophrenia, which complements existing research implicating
      dopamine dysfunction in the disease. According to the NMDA receptor hypofunction
      hypothesis, any treatment that enhances NMDA receptor activity may prove useful
      for the treatment of the complex symptoms that define schizophrenia. This idea is
      now supported by numerous clinical studies that have reported an efficacious
      response following treatment with activators of the NMDA receptor co-agonist
      glycineB site. One area of study, aimed at potentiating the NMDA receptor via
      activation of the glycineB site is small molecule blockade of the glycine
      reuptake transporter type 1 (GlyT1). Broadly, these efforts have focused on
      derivatives of the substrate inhibitor, sarcosine, and non-sarcosine based GlyT1
      inhibitors. Accordingly, the following review discusses the development of both
      sarcosine and non-sarcosine based GlyT1 inhibitors and their current status as
      putative treatments for schizophrenia and other disorders associated with NMDA
      receptor hypoactivity.

PMID- 17017964
TI  - Ligands targeting the excitatory amino acid transporters (EAATs).
AB  - This review provides an overview of ligands for the excitatory amino acid
      transporters (EAATs), a family of high-affinity glutamate transporters localized
      to the plasma membrane of neurons and astroglial cells. Ligand development from
      the perspective of identifying novel and more selective tools for elucidating
      transporter subtype function, and the potential of transporter ligands in a
      therapeutic setting are discussed. Acute pharmacological modulation of EAAT
      activity in the form of linear and conformationally restricted glutamate and
      aspartate analogs is presented, in addition to recent strategies aimed more
      toward modulating transporter expression levels, the latter of particular
      significance to the development of transporter based therapeutics.

PMID- 17017966
TI  - Central serotonin2C receptor: from physiology to pathology.
AB  - Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central
      nervous system (CNS), an enormous amount of experimental evidence has revealed
      the pivotal role of this biogenic amine in a number of cognitive and behavioural
      functions. Although 5-HT is synthesized by a small group of neurons within the
      raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic
      projections. Furthermore, the importance of 5-HT modulation and the fine-tuning
      of its action is underlined by the large number of 5-HT binding sites found in
      the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been
      identified. This review was undertaken to summarize the work that has explored
      the pathophysiological role of one of these receptors, the 5-HT2C receptor, that
      has been emerged as a prominent central serotonin receptor subtype. The
      physiology, pharmacology and anatomical distribution of the 5-HT2C receptors in
      the CNS will be firstly reviewed. Finally, their potential involvement in the
      pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse
      will be also discussed.

PMID- 17017967
TI  - Selective agents for serotonin2C (5-HT2C) receptor.
AB  - The serotonin2C (5-HT2C) receptor has attracted a lot of attention owing to its
      role in appetite regulation, depression, obsessive-compulsive disorder (OCD),
      panic disorders, and substance abuse. This review summarizes non-patent and
      patent literature up to November 2005 that deals with the synthesis and
      characterization of selective 5-HT2C receptor agonists and antagonists.
      Highlights on structure-activity relationships have been included, when possible.

PMID- 17017968
TI  - Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of
      psychostimulant use and dependence.
AB  - The development of novel pharmacological agents for the treatment of
      psychostimulant use disorders is an important research imperative. One potential
      target system that has been largely overlooked is the serotonin (5-HT)
      neurotransmitter system. Preclinical studies indicate that 5-HT may be important
      in modulating the reinforcing properties of various drugs of abuse. While the
      potential sites of action of 5-HT within the brain are extensive, the natural
      starting point to examine the mechanisms by which 5-HT may be useful in treatment
      of psychostimulant use disorders is the interaction between 5-HT and dopamine
      (DA), a primary mediator of the "rewarding" effects of psychostimulants. Two key
      modulators of DA output are the serotonin (5-HT)2A receptor (5-HT2A R) and the 5
      HT2C R. These receptors are known to control the neurochemical and behavioral
      effects of psychostimulants, and in particular, the in vivo effects of cocaine.
      Preclinical studies indicate that 5-HT2A R antagonists and/or 5-HT2C R agonists
      may effectively reduce craving and/or relapse, and likewise, enhance abstinence,
      while 5-HT2C R agonists may also effectively reduce cocaine intake in active
      cocaine users. At present, the progression of studies to probe the effectiveness
      of 5-HT2A R and 5-HT2C R ligands in the clinical setting is hindered by a lack of
      available selective 5-HT2A R antagonists or 5-HT2C R agonists for use in human
      cocaine abusers. However, a number of selective 5-HT2 R ligands currently under
      development, or in early clinical trials for psychiatric and/or neurological
      disorders, may soon be available for translational studies to explore their
      effectiveness in modulating drug use and dependence.

PMID- 17017969
TI  - Serotonergic modulation of spinal sensory circuits.
AB  - The role of serotonin (5-HT) as a mediator of the endogenous pain control system
      has been investigated over the last 30 years. Here we review a subset of studies
      that used electrophysiological techniques to study the mechanisms of action as
      well as the receptors mediating the spinal effects of serotonin. The works herein
      discussed employed in vivo or in vitro preparations of control or hyperalgesic
      animals. According to these reports, 5-HT triggers depressant effects on synaptic
      transmission limiting the release of neurotransmitters from afferent terminals or
      the responsiveness of NMDA receptors located in dorsal horn neurones. These
      mechanisms are most likely mediated by 5-HT1 receptors. In contrast, 5-HT2
      receptors seem to mediate excitatory effects such as depolarisation, increased
      excitability, and neurotransmitter release. The role of 5-HT3 receptors is less
      clear as they could mediate excitatory or inhibitory effects, depending on
      variables such as concentration of 5-HT or the state (sensitised/unsensitised) of
      the spinal cord. The consequences of these spinal effects of serotonin are
      discussed in the context of pain and analgesia.

PMID- 17017970
TI  - The role of 5-HT1A receptors in research strategy for extensive pain treatment.
AB  - In the last few years, there has been a great increase in our understanding of
      pain mechanisms. Given the complexity of the mechanisms involved in pain
      modulation, it is surprising that the pharmacological control of pain through the
      application of relatively simple analgesics can be effective. Nevertheless, the
      application of single analgesics is not always effective in diverse painful
      conditions such as chronic pain syndromes. In these circumstances, we can take
      advantage of the complexity of pain regulation and try to identify new targets in
      these intricate processes. It is becoming clear that the combination of different
      mechanisms, which improves efficacy with reduced toxicity, is necessary for the
      reliable pharmacotherapy of pain, and is at the forefront in the search for
      better analgesics. Serotonin is involved at multiple levels in the regulation of
      nociception. In particular, the raphe nuclei may play a crucial role in
      integrating the nociceptive and affective information through descending
      projections to the spinal cord and ascending projections to the forebrain. In
      these nuclei, 5-HT1A receptors function as somatodendritic autoreceptors
      controlling the release of serotonin in terminal areas. Different studies have
      shown that, by preventing this inhibitory control of serotonin release, it is
      possible to enhance the analgesic effect of drugs that increase serotonin levels
      (i.e. antidepressants, opiates, and non-steroidal anti-inflammatory drugs) by
      facilitating descending, and also ascending, pathways involved in pain
      modulation. Therefore, 5-HT1A receptors may be used as a new target in the search
      for new pharmacological approaches in the augmentation of analgesia.

PMID- 17017971
TI  - Pharmacophore models for metabotropic 5-HT receptor ligands.
AB  - An overview of pharmacophore models, developed for different subtypes of
      serotonin receptors belonging to the GPCR family, is presented. Starting with
      early models for 5-HT1A and 5-HT2 receptor ligands, and ending with the latest
      ones for 5-HT6- and 5-HT7 receptors, as many as fifty others are briefly
      summarized. No models have been developed for 5-HT1F-, 5-HT2B- and 5-HT5B
      receptor ligands, and in the case of 5-HT1E- and 5-HT5A Rs only single pilot
      studies with non-selective tryptamine derivatives are reported. For all the other
      subtypes of 5-HTRs, various pharmacophore hypotheses--either qualitative and/or
      quantitative--are characterized by sets of ligands used for their generation, a
      templates for alignment, the computational methods applied and, eventually,
      interfeature distances and/or statistical results--if available.

PMID- 17017972
TI  - PET and SPET molecular imaging: focus on serotonin system.
AB  - Emission tomography techniques and, in particular, positron emission tomography
      (PET) enable the in vivo study of several physiological and neurochemical
      variables in human subjects using methods originally developed for quantitative
      autoradiography. In particular, PET allows one to evaluate in human subjects: (a)
      the effect of specific neurochemical challenges on regional brain function at
      rest or under activation; (b) the activity of neurotransmitters and the regional
      expression of specific molecular targets during pathology including their
      modulation by drug treatment; (c) the kinetics of drug disposition and activity
      directly in the target organ. This is of primary interest in the field of
      biological psychiatry and in psychoactive drugs development, where it is
      particularly difficult to reproduce human diseases using animal models in view of
      the peculiarity of this field and the large heterogeneity of each psychiatric
      illness also inside the same clinical definition. The aim of this paper is to
      review the principal strategies and the main results of the use of PET or single
      photon emission tomography (SPET) molecular imaging for the in vivo study of
      serotonin receptors and the main results obtained from their application in the
      study of major depression.

PMID- 17017973
TI  - New treatment options using 5-HT3 receptor antagonists in rheumatic diseases.
AB  - In vitro studies have shown that a blockade of 5-HT3 receptors brings about a
      reduction of tumor necrosis factor, IL-1 beta, IL-2, IL-6 as well as a decrease
      in prostaglandins. Clinical trials have provided evidence of pain reduction in a
      subgroup of fibromyalgia syndrome and, moreover, have demonstrated that
      tropisetron injected locally for insertion tendinoses and myofascial syndromes
      with associated trigger points leads to an alleviation of pain that is comparable
      to injections with the combination of corticosteroids and local anesthetics. The
      effects achieved by intra-articular injections in cases of osteoarthritis and
      rheumatoid arthritis paralleled those exerted by intraarticular injection of
      corticosteroids. In addition, the positive effects produced by systemically
      administered tropisetron on scleroderma need to be considered since they suggest
      that this therapeutic principle can also be applied systemically in immunologic
      processes.

PMID- 17017974
TI  - Targeting tumor-related immunosuppression for cancer immunotherapy.
AB  - Tumors produce several factors, such as Prostaglandins (PGs), Interleukin (IL)
      10, Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor
      (TGF)-beta, which may directly or indirectly inhibit the immune response and may
      hamper immunotherapy. Furthermore, cells of innate or adaptive immunity,
      recruited by tumor-derived factors, may contribute in immunosuppression.
      Regulatory T (Treg) cells such as the "naturally occurring" CD4(+)/CD25(+) Treg
      and the IL-10-induced Tr1 cells are major players in this arena. Paradoxically
      Treg cells are stimulated by IL-2, which is used in tumor immunotherapy. Treg
      cells suppress T cell responses through soluble factors or by contact-dependent
      mechanisms, such as the Cytotoxic T Lymphocyte Antigen (CTLA)-4-mediated
      induction of Indoleamine 2,3-Dioxygenase (IDO) in dendritic cells (DC). IDO
      inhibits T cell responses by depleting Tryptophan and producing Kynurenine, which
      is toxic to lymphocytes. Macrophages, granulocytes or myeloid suppressor cells
      (MSC) suppress immunity by other enzymatic mechanisms, involving Arginase and
      Nitric Oxide Synthase (NOS). Subversion of tumor immunosuppression is required
      for successful immunotherapy. Attempts to block or eliminate Treg cells have been
      made by the use of chemotherapy, anti-CD25 or anti-CTLA-4 antibodies, IL-2-toxin
      chimeric proteins or Glucocorticoid-induced TNF-like Receptor (GITR) and CD134/OX
      40 ligands. Tumor cells genetically modified to secrete IL-21 (an immune
      stimulatory "IL-2-like" cytokine, which is not involved in immune regulation)
      cured experimental metastases in combination with anti-CD25 monoclonal antibodies
      (mAbs). Also strategies aimed at blocking enzyme-based immune-suppressive
      mechanisms are suitable, as suggested by experimental evidences in mouse tumor
      models.

PMID- 17017975
TI  - Drug therapy aimed at adenylyl cyclase to regulate cyclic nucleotide signaling.
AB  - Conventional drug screening has been targeted, in many cases, on cell surface
      receptors, e.g., G-Protein coupled receptors, to regulate cellular signaling and
      thus function. There is emerging evidence, however, that such targets can be
      expanded to effector enzymes of receptors because effector enzymes have multiple
      subtypes that differ in tissue distribution, and thus targeting such molecules
      may lead to organ-specific pharmacological regulation. An example is
      phosphodiesterase, which degrades cyclic nucleotides. Subtype-specific
      phosphodiesterase inhibitors, such as sildenafil citrate, a type 5
      phosphodiesterase inhibitor, and milrinone, a type 3 phosphodiesterase inhibitor,
      are now widely used in the treatment of erectile dysfunction and heart failure,
      respectively. Adenylyl cyclase, which synthesizes cyclic AMP, has at least 9
      isoforms that differ in tissue distribution. Transgenic mouse studies utilizing
      such isoforms have identified the roles of each isoform. Forskolin, a natural
      plant extract, was first identified as a general stimulator of adenylyl cyclase
      more than 20 years ago. Recently, 6-[3-(dimethylamino)propionyl]forskolin, a
      water-soluble forskolin derivative with high selectivity for type 5 (cardiac)
      adenylyl cyclase was developed and has been widely used in the treatment of acute
      heart failure. Adenine analogs or P-site inhibitors, which are classic, but not
      isoform-specific adenylyl cyclase inhibitors, are now utilized to develop isoform
      specific inhibitors as well. Putting together, targeting adenylyl cyclase
      isoforms, either of isoform-specific stimulation or inhibition, may be a novel
      strategy to develop new drugs in the next decade.

PMID- 17017976
TI  - Vasopressin-receptor antagonists: a new class of agents for the treatment of
      hyponatremia.
AB  - Hyponatremia is a very common electrolyte disorder often caused by the
      dysregulation of arginine vasopressin (AVP) secretion and the effects of the
      hormone at its receptors and is associated with significant morbidity and
      mortality. Recent developments in the understanding of water homeostasis and AVP
      actions at the kidney, both in normal circumstances and in pathologic conditions,
      has created the possibility of new therapies that directly target the
      inappropriate excess of AVP stimulation of vasopressin V(2) receptors (V2Rs) in
      the kidney. Preclinical and clinical trial results indicate that AVP V2R
      antagonism is a highly promising and rational approach for the treatment of
      dilutional hyponatremia caused by excessive retention of water. This review of
      hyponatremia and its therapy is intended to educate clinicians who manage
      patients who have hyponatremia and its complications. Background information on
      hyponatremia is presented and the pertinent published literature with regard to
      the diagnosis and therapy of this disorder is summarized with a specific focus on
      AVP-receptor antagonists. Agents that antagonize AVP V2Rs and promote aquaresis,
      the electrolyte-sparing excretion of free water, are likely to be effective and
      well tolerated therapies for the treatment of dilutional hyponatremia.

PMID- 17017977
TI  - Type 1 11beta-hydroxysteroid dehydrogenase as universal drug target in metabolic
      diseases?
AB  - Glucocorticoid hormones play essential roles in adaptation to stress, regulation
      of metabolism and inflammatory responses. Their effects primarily depend on their
      binding to intracellular receptors leading to altered target gene transcription
      as well as on cell-type specific biotransformation between 11beta-hydroxy
      glucocorticoids and their 11-oxo metabolites. The latter effect is accomplished
      by two different 11beta-hydroxysteroid dehydrogenase isozymes, constituting a
      shuttle system between the receptor ligand cortisol and its non-binding precursor
      cortisone. Whereas the type 1 enzyme (11beta-HSD1) is in vitro a NADP(H)-
      dependent bidirectional enzyme, it reduces in most instances in vivo cortisone to
      active cortisol. The type 2 enzyme is an exclusive NAD+ dependent dehydrogenase
      of glucocorticoids, thus "protecting" the mineralocorticoid receptor against
      illicit occupation by cortisol. Inhibition of tissue-specific glucocorticoid
      activation by 11beta-HSD1 constitutes a promising target in the treatment of
      metabolic and cardiovascular diseases. Pharmacological inhibition leads in animal
      models to lowered hepatic glucose production and increased insulin sensitivity,
      the primary goals in therapy of diabetes mellitus. Importantly, 11beta-HSD1
      activity appears to be intrinsically linked to all features of the metabolic
      syndrome, which could at least in animal experiments be modulated by use of
      synthetic selective inhibitors. Importantly, these features include not only
      insulin resistance but also dyslipidemia, obesity and arterial hypertension.
      Animal studies and pharmacological experiments suggest further unrelated target
      areas, for example improvement of cognitive function and treatment of glaucoma,
      due to the role of glucocorticoids and cellular activation by 11beta-HSD1 in
      these pathologies. The recent development of specific 11beta-HSD1 inhibitors
      coupled with advances on structural knowledge and regulation of the 11beta-HSD1
      target has undoubtedly promoted the understanding of glucocorticoid control of
      metabolic regulation. Taken together, it appears that inhibitors against 11beta
      HSD1 constitute a promising avenue for novel treatment strategies against the
      underlying causes of cardiovascular and other metabolic diseases.

PMID- 17017978
TI  - Drug targets to pro-angiogenetic factors with special reference to primary
      peritoneal mesothelioma.
AB  - Angiogenesis is necessary for growth and the spread of human tumors. Animal
      studies also suggest that angiogenesis is an important interspecies biological
      mechanism of tumor development. Angiogenesis is a complex multistep cascade
      modulated by both positive soluble factors, such as vascular endothelial growth
      factor, thymidine phosphorylase, basic-fibroblast growth factor and negative
      soluble factors such as angiostatin and endostatin. From the imbalance of the
      above angiogenesis regulators, tumor endothelial cells may divide up to 50 times
      more frequently than endothelial cells of normal tissue. Published studies have
      suggested that the assessment of microvessel density (MVD) or endothelial area
      (EA) can be considered as surrogate markers of angiogenesis with biological and
      prognostic relevance. Literature data on angiogenesis of mesothelioma are
      inconclusive, with only a few studies performed in primary peritoneal
      mesothelioma (PPM) due to the rarity of the disease. We assessed
      immunohistochemically MVD and EA and their biological and clinical significance
      in a consecutive series of 23 PPM cases. MVD and EA were detected in "hot spots"
      by a computerized image analyzer. The mean value of MVD and EA was 27 +/- 14 and
      26.04 +/- 8.35 x10(-2) micro(2) per field (400x), respectively. Patients with a
      high MVD or EA tumors showed a more clinical aggressiveness due to the presence
      of ascites and a shorter overall survival. Our results suggest that PPM is an
      angiogenesis-dependent neoplasia. Therefore, antiangiogenic compounds should be
      tested particularly in those patients with highly vascularized PPM.

PMID- 17017979
TI  - Antioxidant effects of glutathione and IGF in a hyperglycaemic cell culture model
      of fibroblasts: some actions of advanced glycaemic end products (AGE) and
      nicotine.
AB  - The aim of this investigation was to establish potential oxidative effects of
      glucose, advanced glycation end products (AGE) and nicotine (N) in a fibroblast
      cell culture model using the anti-oxidants glutathione (G) and insulin like
      growth factor (IGF). Assays of androgen metabolites were used as biomarkers of
      healing in this context. Confluent monolayer cultures of human gingival
      fibroblasts were established in 24 well multiwell plates and incubated in Eagle's
      MEM for 24h using two radiolabelled androgen substrates 14C-testosterone/14C-4
      androstenedione. The established effective concentrations of G1000, glutathione
      and AGE were used alone and in combination with nicotine and insulin-like growth
      factor. The medium was then solvent extracted for steroid metabolites, evaporated
      to dryness and subjected to thin layer chromatography in a benzene acetone
      solvent system 4:1 v/v for separation of formed metabolites. The metabolites were
      quantified, using a radioisotope scanner. Significant reduction in the yields of
      DHT in response to G1000, AGE and nicotine (n=6; p <0.003) were overcome by
      glutathione (n=6; p <0.002). The stimulatory effect of IGF when combined with AGE
      was further enhanced by the antioxidant effect of glutathione (n=6; p <0.003).
      Glucose, AGE and nicotine had a significant inhibitory effect on the yields of
      the androgen biomarker DHT, overcome by the antioxidant glutathione and IGF,
      suggestive of an oxidant role for the former agents and an anti-oxidant one for
      the latter. These agents affected yields of androgen metabolites, biomarkers of
      oxidative stress and repair, with potential implications on healing in
      uncontrolled diabetic smokers.

PMID- 17017981
TI  - Anthracyclines-contra cruciform extrusion in DNA regulating sequences.
AB  - Despite the existence of a wealth of structural and theoretical data relating to
      palindromic sequences in the genome, the mechanism of cruciform formation in the
      presence of anthracyclines in miscellaneous biological processes is still poorly
      understood. Generally, DNA intercalators influence the DNA superhelicity, which
      plays a key role in the cruciform formation in DNA molecules. The potential of
      DNA intercalating ligands on the stabilization/destabilization of cruciform in
      DNA is discussed. Here, the indirect impact of anthracyclines to cell developing
      and surviving is analyzed for the first time. Primarily, the anthracycline
      modifies the helical properties of DNA and the overall DNA structure, and
      secondarily alters any cruciform-dependent processes, mainly DNA replication and
      transcription.

PMID- 17017980
TI  - Origin and biological significance of shed-membrane microparticles.
AB  - Microparticles (MPs) are small vesicles released from the membrane surface during
      eukaryotic cell activation or apoptosis. They originate from various cell types,
      displaying the typical surface cell proteins and cytoplasmic components of their
      cell origin. Their procoagulant properties are linked to phosphatidylserine
      exposed at their surface. Numerous reports have shown that MPs are able to
      mediate long-range signaling, acting on different targets from those of their own
      cellular origin. MPs-mediated binding to other cells occurs by integration into
      the membrane, by adhesion to the cell surface or by ligand-receptor interaction.
      Elevated levels of circulating MPs have been detected in cardiovascular and
      immune-mediated diseases. Despite extensive studies of the procoagulant and pro
      inflammatory properties of MPs, little is known about their effect on vascular
      function. MPs accumulate in atherosclerotic plaques and injured vascular wall.
      Circulating MPs from patients with myocardial infarction induce endothelial
      dysfunction by impairing the endothelial nitric oxide (NO) pathway, without
      causing changes in endothelial NO-synthase (eNOS) expression. However, MPs from T
      cells may induce endothelial dysfunction, altering gene expression of eNOS and
      caveolin-1. Moreover, MPs may promote the expression of pro-inflammatory proteins
      implicated in vascular contractility alterations. This review describes the
      origin of MPs and their biological role in physiological conditions and in
      various pathological states, with special reference to the possible linkage
      between their pro-inflammatory and procoagulant properties and vascular
      dysfunction.

PMID- 17017982
TI  - Evaluation of the cytotoxic and pro-apoptotic activities of Eu(III) complexes
      with appended DNA intercalators in a panel of human malignant cell lines.
AB  - A series of 8 europium (III) tris-beta-diketonates with common formula
      Eu(L)(3)Int, where L is acetyl acetone, thenoyltrifluoroacetone, benzoylacetone,
      dibenzoylmethane and Int is 1,10-phenanthroline or 2,2'-bipyridine, together with
      an analog without intercalating moiety (Eu(III)(acetyl acetone)(3)(H(2)O)(2))
      were tested for cytotoxic activity in a panel of human tumor cell lines, using
      the MTT-dye reduction assay. The panel consisted of the leukemias HL-60, BV-173,
      SKW-3, K-562, LAMA-84 and the urinary bladder carcinoma 5637. The tested europium
      complexes with appended intercalator moieties exhibited profound cytotoxic
      effects with IC(50) values lower or comparable to those of the referent drug cis
      DDP, whereby the 1,10-phenanthroline bearing compounds were invariably more
      active than the corresponding 2,2'-bipyridine analogs. The established low
      cytotoxic potential of Eu(III)(acetyl acetone)(3)(H(2)O)(2) as compared to its
      highly potent analogs with either 1,10-phenanthroline or 2,2'-bipyridine ligand
      demonstrated that the abundance of intercalating motif is a mandatory structural
      prerequisite for optimal activity within this series of cytotoxic agents.
      Selected compound caused DNA-fragmentation when applied in cytotoxic
      concentration, which suggests that the induction of programmed cell death
      (apoptosis) at least partly mediates the cytotoxic effects of tested compounds.
      Taken together our data give us reason to conclude that the presented Eu(III)
      complexes represent a unique class of cytotoxic metal coordination compounds and
      necessitate further detailed evaluation in order to define the structure activity
      relationships as well as the predominant mode of action. To the best knowledge of
      the authors this is among the first reports of potent cytotoxic Eu(III)
      compounds.

PMID- 17017983
TI  - Interactions between oxicams and membrane bilayers: an explanation for their
      different COX selectivity.
AB  - Meloxicam was launched as a major new NSAID for the treatment of arthritis
      following extensive published research confirming its selectivity for COX-2.
      Several studies proposed possible explanations for its effectiveness and superior
      safety profile. The proposed theories included chemical structural relationships
      between meloxicam and other effective NSAIDs with low gastrointestinal toxic
      effects. However, other oxicams have similar chemical groups, but despite this,
      are not considered COX-2 selective drugs and exhibit less gastric tolerance.
      Hence, the aim of this work was to investigate the interactions between oxicams
      and biomembrane models as it could influence their resorption from the upper
      gastrointestinal tract and may affect their local gastromucosal tolerability. The
      partition of oxicams within membranes was determined by calculating their
      partition coefficients between liposomes and water. Moreover, their location
      within the bilayer was determined by fluorescence quenching. Finally, zeta
      potential measurements were made to complete the information about the binding
      behaviour of the oxicams and steady-state anisotropy measurements were made to
      determine their induced perturbation in membrane structure. These studies proved
      that, in spite of structural similarities, oxicams present different interactions
      with membranes making possible a virtual division of the class in two groups.
      Tenoxicam and piroxicam known as COX-1 inhibitors demonstrated higher partition
      capacity in liposomes/water systems together with a smaller ability to change the
      membrane fluidity and surface potential. In contrast lornoxicam and meloxicam,
      which demonstrated activity against COX-2, have revealed smaller partition
      capacity in liposomes/water systems together with a higher ability to change the
      membrane fluidity and surface potential.

PMID- 17017984
TI  - The effects of all-trans-retinoic acid on cell cycle and alkaline phosphatase
      activity in pancreatic cancer cells.
AB  - Pancreatic cancer is one of the tumors with the highest mortality, poorly
      responding to available chemotherapeutic agents. The objective of this study was
      to study the anticancer effects of all-trans retinoid acid, a functional form of
      vitamin A, on pancreatic cancer cells. Human pancreatic cancer MiaPaCa-2 cells
      were treated with 1, 5, 10, 20, 30, 40 and 50 microM ATRA for 1, 2, 3, 4, 5 or 6
      d, respectively. Cell growth was determined by MTT viability assay. The cell
      cycle distribution and the alkaline phosphatase (ALP) activity were analyzed by
      flow cytometry and chemical analyzer, respectively. The results show that ATRA
      significantly inhibited the growth of MiaPaCa-2 cells at 40 and 50 microM. ATRA
      arrested pancreatic cancer cells at G0/G1 phase. The sub-G1 peak and DNA
      fragmentation were observed. There were time and dose dependent increases in
      alkaline phosphatase activity (ALP), an indicator of cell differentiation, upon
      treatment with ATRA when compared to controls. In conclusion, ATRA has an
      inhibitory effect on the cell growth of MiaPaCa-2, and its tumor suppressive
      effect is by means of cell cycle arrest and apoptosis induction.

PMID- 17017985
TI  - Cerium(III) and neodymium(III) complexes as scavengers of X/XO-derived superoxide
      radical.
AB  - The cerium (III) and neodymium (III) complexes with 3,3'-benzylidenebis[4
      hydroxycoumarin] were synthesized and characterized by different analytical and
      spectral methods. The synthesis of these complexes is taken into consideration
      with cytotoxic screening and study of their antioxidant effect. Their
      cytotoxicity toward cancerous cell cultures correlated with the weakness of the
      coordinative bond between the cation and organic ligand and with the capability
      to scavenge superoxide radicals as well. On the basis of the data reported by us
      earlier and our new results, it was proposed that cerium (III) complex with 3,3'
      benzylidenebis[4-hydroxycoumarin] might induce intracellular acidification along
      with control over the extracellular oxidative stress.

PMID- 17017986
TI  - Avoidance of Abeta[(25-35)] / (H(2)O(2)) -induced apoptosis in lymphocytes by the
      cannabinoid agonists CP55,940 and JWH-015 via receptor-independent and PI3K
      dependent mechanisms: role of NF-kappaB and p53.
AB  - Cannabinoids have been suggested as potential neuroprotective compounds in
      Alzheimer's disease (AD). Despite intense investigation, the detailed
      intracellular mechanism(s) involved in cannabinoids survival effect remains to be
      elucidated. The present study shows that CP55,940 (a CB1 and CB2 agonist) and JWH
      015 (a CB2 agonist) protect and rescue peripheral blood lymphocytes (PBL) from
      (10 microM) Abeta[(25-35)] and (50 microM) H(2)O(2)-induced apoptosis by two
      alternative mechanisms: (1) receptor-independent pathway, as demonstrated by no
      dihydrorhodamine oxidation into fluorescent rhodamine 123 (R-123) as a result of
      cannabinoid inhibition of Abeta-generated H(2)O(2); (2) receptor-dependent
      pathway through NF-kappaB activation and p53 down regulation involving
      phosphoinositide 3-kinase (PI-3K), as demonstrated by using either (25 microM)
      LY294002 (a PI-3K inhibitor), (50 nM) pifithrin-alpha (PFT, a specific p53
      inhibitor) or by using immunocytochemistry detection of NF-kappaB and p53
      transcription factors activation. Importantly, cannabinoid agonists and PFT were
      able to protect and rescue lymphocytes pre-exposed to toxicants-, even when the
      three compounds were added up-to 12 h post-Abeta[(25-35)]/(H(2)O(2)) exposure.
      These results suggest that CP55,940/( JWH-015) protection/rescue of PBL from
      noxious stimuli is determined by p53 inactivation. These findings may contribute
      to a better understanding of the role played by cannabinoids as neuroprotective
      agents to target and interrupt molecular signaling that induce damage in AD
      disorder.

PMID- 17017987
TI  - A first QSAR model for galectin-3 glycomimetic inhibitors based on 3D docked
      structures.
AB  - This study presents the first QSAR model for Galectin-3 glycomimetic inhibitors
      based on docked structures to the carbohydrate recognition domain (CRD).
      Quantitative numerical methods such as PLS (Partial Least Squares) and ANN
      (Artificial Neural Networks) have been used and compared on QSAR models to
      establish correlations between molecular properties and binding affinity values
      (Kd). Training and validation of QSAR predictive models was performed on a master
      dataset consisting of 136 compounds. The molecular structures and binding
      affinities (Kd) (136 compounds) were obtained from the literature. To address the
      issue of dimensionality reduction, molecular descriptors were selected with PLS
      contingency approach, ANN, PCA (Principal Component Analysis) and GA (Genetic
      Algorithms) for the best predictive Galectin-3 binding affinity (Kd). Final sets
      comprising 56, 31 and 35 descriptors were obtained with PLS, PCA and ANN,
      respectively. The objective of this prototype QSAR model is to serve as a first
      guideline for the design of novel and potent Gal-3 selective inhibitors with
      emphasis on modification at both C-3' and at O-3 positions.

PMID- 17017988
TI  - Molecular dynamics model of unliganded HIV-1 reverse transcriptase.
AB  - HIV-1 RT is one of the most important antiviral targets in the treatment of
      acquired immunodeficiency syndrome (AIDS). Several crystallographic structures
      are available for this enzyme, mostly with bound inhibitors. Despite their
      importance for structure based drug design towards new anti-HIV retrovirals, the
      X-ray structures of the unliganded enzyme could only be obtained incomplete, with
      a low resolution and until recently even the conformation of the p66 thumb was
      controversial. In this work we have aligned different X-ray RT structures, and
      built up a computational model of RT using homology modeling, which was
      afterwards refined and validated through MD simulations with explicit solvent.
      The model enzyme was structurally stable through the whole MD simulation, showing
      a RMSD of 2 Angstrom from the starting geometry. The Ramanchandram plot has
      improved along the simulation. Both intra-domain and interdomain movements were
      observed. The thumb kept its closed conformation through the whole simulation. A
      contact map, hydration sites study and a detailed analysis of the solvation of
      the nucleotide binding site are also presented.

PMID- 17017989
TI  - Airway epithelium directed gene therapy for cystic fibrosis.
AB  - Gene therapy is a promising therapeutic modality for the treatment of cystic
      fibrosis (CF). Despite a better understanding of the molecular organization of
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene and mutations
      resulting in pathophysiological and phenotypic alterations, several forms of
      treatments including gene therapy have failed to yield clinical success. Major
      limitations for the delivery of drugs and gene therapy vectors from reaching
      target cells in CF patients lie in physical and immunological barriers of airway
      epithelium. Over the last decade, non-viral and viral gene therapy approaches
      have been tested in preclinical studies and human clinical trials of CF. Outcomes
      of these studies have helped to identify hurdles that need to be overcome before
      such approaches can be routinely applied to patients. In addition to the
      physiological and immunological barriers of airway epithelium, vector
      transduction is also impaired by the absence or low-abundance of cellular
      receptors and co-receptors for viral binding and internalization. Thus, the
      initial enthusiasm for gene replacement therapy for CF following cloning of the
      CFTR gene dampened, as more limitations were recognized. Research directed
      towards improving the efficiency of gene transfer technology in CF, is focused on
      testing of compounds to enhance vector permeability and trafficking,
      identification and development of vectors which can transduce through alternate
      pathways, identification of airway epithelium-specific targeting ligands, and the
      identification of stem cells for combining cell therapy and gene therapy by ex
      vivo methods. Details provided in this article will give a comprehensive analysis
      of the prospects and limitations in CF gene therapy using viral and non-viral
      vectors.

PMID- 17017990
TI  - New antifolate inhibitors for Mycobacterium avium.
AB  - The present study extends our previous work regarding new antifolates for
      Mycobacterium avium (MAC) dihydrofolate reductase (DHFR). The objectives of this
      study were to synthesize and test new derivatives in the general class of 2,4
      diamino-5-methyl-5-deazapteridines in an effort to improve solubility and
      selectivity for the MAC DHFR, while maintaining lack of selectivity for the human
      DHFR. New 6-[2', 5'-dialkoxyphenyl) methyl]-substituted DMDP analogs were
      synthesized as previously described. Three clinical isolates of MAC (NJ211,
      NJ3404, and NJ168) and M. tuberculosis H37Ra (MTB) were used to evaluate the new
      derivatives. A previously described colorimetric (alamarBlue(R)) microdilution
      broth assay was used to determine minimal inhibitory concentrations (MIC).
      Purified recombinant human (rDHFR), MAC rDHFR, and MTB rDHFR were used in a
      validated enzyme assay to obtain IC(50) values and to determine selectivity
      ratios (SR) for the derivatives. For the MAC strains, the MICs ranged from < 0.25
      to > 16 microg/mL. The most active derivative against MAC was SRI-20920 which had
      MICs of 0.25, 0.25, and 8 microg/mL for the three strains, respectively. The most
      selective derivative was SRI-20730 with IC(50s) of 29 and 67,781 nM for MAC rDHFR
      and hDHFR, respectively, and a SR of 2,337. MICs for MTB ranged from 4 to >64
      microg/mL and the SR, in general, ranged from 0.32 to 2.5. These results further
      substantiate the utility of this group of DMDP derivatives for selective activity
      against MAC.

PMID- 17017991
TI  - Phenazine 5,10-dioxide derivatives as hypoxic selective cytotoxins: Part II.
      Structure-activity relationship studies.
AB  - The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives
      of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were
      developed as structural analogs of other bioreductive compounds and its in vitro
      cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined.
      To gain insight into its mechanism of action electrochemical behavior,
      interaction with DNA experiments and QSAR studies were performed.

PMID- 17017992
TI  - Matrix metalloproteinase (MMP)-7 activates MMP-8 but not MMP-13.
AB  - Matrix Metalloproteinases (MMPs) are a class of zinc-dependent enzymes that
      degrade extracellular matrix components, particularly collagen. MMPs have been
      implicated in a diverse list of pathological processes, including cancer and
      cardiovascular disease. Recent efforts to bring MMP inhibitors to clinical
      trials, however, have proved disappointing. These failures are attributed, in
      part, to the non-selective nature of current inhibitors. The possibility also
      exists, however, that inhibition of a particular MMP type will lead to feedback
      accumulation of parallel MMP members. MMP-7, also known as matrilysin, has a
      broad list of substrates, including denatured collagen and other MMPs involved in
      the collagenolytic pathway, namely MMP-1, MMP-2, and MMP-9. Whether the
      additional collagenases, MMP-8 and MMP-13, are also activated by MMP-7 has not
      been explored. We show here that recombinant active MMP-7 was able to process MMP
      8 to its active form in vitro, but did not activate MMP-13. In the left
      ventricles of mice lacking the MMP-7 gene, MMP-8 levels increased while MMP-13
      levels decreased in vivo. The switch in MMP profile was not accompanied by a
      change in left ventricular dimensions or wall thickness. Together, these data
      suggest that MMP-8 is an in vivo substrate of MMP-7, and that the accumulation of
      pro-MMP-8 in the absence of MMP-7 downregulates pro-MMP-13 levels in order to
      maintain baseline collagenolytic function. The interplay between MMP-8 and MMP-13
      suggest that these MMPs may play reciprocal roles. The design of selective MMP
      inhibitors, therefore, must take into consideration changes in parallel MMP types
      as a potential compensatory mechanism.

PMID- 17017993
TI  - Vasodilator effects of bis-dihydropyridines structurally related to nifedipine.
AB  - Calcium channel blockers are widely used in therapy for hypertension and angina
      pectoris, and among these blockers some 1,4-dihydropyridines (e.g. amlodipine,
      nitrendipine and nifedipine) have had widespread clinical use. In this work we
      investigated the vascular effects of four bis-1,4-dihydropyridines (bis-DHPs: 01
      04), structurally related to nifedipine, in which a second 1,4-dihydropyridinic
      moiety was incorporated in the corresponding arylic moiety in para and meta
      position. Of these four bis-DHPs, the meta regioisomers (bis-DHP-03 and bis-DHP
      04; 0.01-3.16 mg kg(-1)) and nifedipine induced a greater decrease on diastolic
      and systolic blood pressure than the para isomers (bis-DHP-01 and bis-DHP-02), as
      shown in two experimental models: normotensive and spontaneously hypertensive
      rats. Complementarily, bis-DHPs action was examined in intact and endothelium
      denuded rat aorta, depolarized by KCl [80 mM] in one group and stimulated by
      noradrenaline (1 x 10(-7) M) in another and the corresponding IC(50) values were
      obtained (1.5 x 10(-6)-2. 4 x 10(-7)M). Later, the relaxing action of bis-DHP
      03,04 and nifedipine on the contraction evoked by Ca(2+) in K(+)-depolarized rat
      aorta was analyzed and the corresponding EC(50) values for the meta isomers and
      nifedipine were obtained. The results showed a concentration dependent
      vasodilating activity in both KCl precontracted and noradrenaline stimulated
      aorta rings. The apparent order of potency with and without endothelium in both
      experimental models was nifedipine >bis-DHP-04 >bis-DHP-03. The cumulative
      concentration-effect curves for Ca(2+) in the presence of the bis-DHPs tested
      show the same potency order. Unlike nifedipine, the tested compounds are not
      photosensitive, which makes them more attractive in therapy for hypertension
      related diseases.

PMID- 17017994
TI  - N-type calcium channel blockers: novel therapeutics for the treatment of pain.
AB  - Highly selective Ca(v)2.2 voltage-gated calcium channel (VGCC) inhibitors have
      emerged as a new class of therapeutics for the treatment of chronic and
      neuropathic pain. Cone snail venoms provided the first drug in class with FDA
      approval granted in 2005 to Prialt (omega-conotoxin MVIIA, Elan) for the
      treatment of neuropathic pain. Since this pioneering work, major efforts underway
      to develop alternative small molecule inhibitors of Ca(v)2.2 calcium channel have
      met with varied success. This review focuses on the properties of the Ca(v)2.2
      calcium channel in different pain states, the action of omega-conotoxins GVIA,
      MVIIA and CVID, describing their structure-activity relationships and potential
      as leads for the design of improved Ca(v)2.2 calcium channel therapeutics, and
      finally the development of small molecules for the treatment of chronic pain.

PMID- 17017995
TI  - Hydrophilic carotenoid amphiphiles: methods of synthesis and biological
      applications.
AB  - Carotenoid bioactivity, namely the quenching of reactive oxygen species (ROS) and
      other excited-state oxidants, suggests significant clinical potential for these
      natural products. However, a thorough therapeutic evaluation of the carotenoids
      has been hampered by limited water-solubility and/or water-dispersibility
      ("hydrophilicity") as well as poor bioavailability. Hydrophilic carotenoid
      derivatives have been designed and prepared for parenteral administration.
      Synthetic methods, selected physical characteristics, and potential biological
      applications of these novel therapeutics will be discussed.

PMID- 17017996
TI  - Modulation of catalytic RNA biological activity by small molecule effectors.
AB  - Catalytic RNAs, known as ribozymes, act as true enzymes and are implicated in
      important biological processes, such as protein synthesis, mRNA splicing,
      transcriptional regulation and retroviral replication. Ribozymes are capable of
      serving as a new molecular target for a variety of drugs and as a reliable
      screening system for their biological activity.

PMID- 17017997
TI  - Utilizing peptide structures as keys for unlocking challenging targets.
AB  - Three-dimensional structures of protein targets have proven to be extremely
      valuable for modern drug design and discovery. For cases where the structure of
      the protein is unattainable, such as G-protein coupled receptors (GPCRs),
      structural information on active ligands is still useful and helpful for
      deciphering the geometrical and chemical features of the active site. Peptides,
      constructed from easy-to-form amide backbones and featuring variable side-chains,
      have an inherent advantage in generating rapid quantitative structure-activity
      relationships (QSAR). Given the fact that peptides are natural ligands for many
      protein targets, structural investigation of a series of related peptides,
      typically carried out via nuclear magnetic resonance (NMR), can result in an
      accurate pharmacophore model. Such a model can be used for virtual screening, and
      to assist design of second-generation peptidomimetics with improved properties
      and design of non-peptidic leads. In this article, we will review examples in
      which a structural approach utilizing peptide ligands was employed to obtain a
      better understanding of the target active site. We will focus on cases where such
      information supplied guidance toward the discovery of small molecule ligands.

PMID- 17017998
TI  - The chemokine receptor CXCR4 as a therapeutic target for several diseases.
AB  - CXCR4 is the receptor for a chemokine, CXCL12 (stromal cell-derived factor-1, SDF
      1). The CXCL12-CXCR4 axis has been proven to be involved in several problematic
      diseases, including AIDS, cancer cell metastasis, leukemia cell progression and
      rheumatoid arthritis (RA). Thus, CXCR4 is thought to be an important therapeutic
      target to overcome the above diseases. We have developed several specific CXCR4
      antagonists.

PMID- 17017999
TI  - Historical and current perspectives of neuroactive compounds derived from Latin
      America.
AB  - Plants and invertebrates in Latin America have contributed to a great extent in
      the use, discovery and development of novel neuroactive tools. Significantly,
      these neuroactive drugs have proven to be particularly important for our current
      understanding of the physiology and pharmacology of the nervous system. In
      addition, these discoveries have helped to build the modern and successful
      pharmacological business that we know today. For example, curare helped to
      introduce the use of muscle relaxing agents into modern surgical techniques. The
      discovery of cocaine from the leaves of Peruvian coca plants was instrumental in
      the discovery of local anesthetics. The search and discovery for useful
      neuroactive compounds derived from Latin America has also been ongoing in other
      areas and new applications for quinine, capsaicin and epibatidine were recently
      described. Besides these organic compounds, several peptides produced by spiders
      and other invertebrates to hunt their prey also induce effects in channels and
      membrane receptors at very low concentrations, indicating their high potency and
      selectivity. It is likely that new pharmaceutics will be developed from these
      molecules. The interest to renew the search for new compounds is timely, since
      largely unexplored lands, such as the Amazon and Patagonia, hold an important
      number of plants and animals that contain exciting new active compounds. With the
      introduction of new techniques to isolate, identify and characterize the
      molecular targets and actions of chemical entities, together with the need for
      more potent and selective compounds to treat neurological conditions, it is
      necessary to broaden the current exploratory effort in order to find more
      beneficial uses.

PMID- 17018000
TI  - Structural requirements of heparin and related molecules to exert a multitude of
      anti-inflammatory activities.
AB  - Chronic inflammatory diseases are common and still remain a therapeutic challenge
      for both efficacy and safety reasons. Hence, novel therapeutics addressing these
      issues would for example improve treatment of severe diseases such as psoriasis,
      rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis.
      Inappropriate leukocyte homing to the affected compartments is a common feature
      of these diseases. Heparin and related polysaccharides have been shown to
      interfere with leukocyte homing through a variety of effects distinct from their
      anticoagulant properties. In this review, data on heparin as an anti-inflammatory
      agent are presented. In addition, structure-activity requirements for the anti
      inflammatory properties of heparin are discussed, which should aid the drug
      development based on structurally modified heparin or other sulfated
      carbohydrates for treatment of inflammatory diseases.

PMID- 17018001
TI  - Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in
      inhibitor design.
AB  - Clan CA (papain-like) cysteine proteinases of protozoan parasites are validated
      targets for the rational design of new anti-parasitic chemotherapies. Peptidyl
      and peptidomimetic proteinase inhibitors of differing chemistries limit parasite
      survival in vitro and in vivo. Also, the development of activity-based affinity
      labels has enabled the identification and characterization of potential cysteine
      proteinase targets in situ. This article reviews the biology and physicochemistry
      of parasite proteinases and the ongoing design of peptidyl and non-peptidyl
      inhibitors to generate anti-parasitic compounds of greater efficacy with
      decreased toxicity to the host.

PMID- 17018002
TI  - Anti-tumor therapeutic molecules that target the programmed cell death machinery.
AB  - Apoptosis is a process that governs the elimination of unwanted, damaged, or
      infected cells in most organisms. Defects in its execution are associated with
      several diseases, including cancer. Herein, we discuss novel molecules with
      potential anti-tumor activity that target components of the apoptotic machinery,
      specifically Bcl-2 proteins, IAPs and caspases.

PMID- 17018003
TI  - Glycosylation pathways as drug targets for cancer: glycosidase inhibitors.
AB  - The combined and ordered sequential action of glycosidases and
      glycosyltransferases in mammalian cell compartments leads to the addition of
      defined glycans to proteins and lipids. Altered glycosylation patterns,
      neoexpression, underexpression or overexpression of glycans are a hallmark of
      cancer. These changes are either found in the core or the terminal structures of
      the carbohydrates of glycoproteins. Affected proteins can be either cellular,
      cell-surface or secreted proteins, and glycosylation modifications frequently
      result in a modified expression, metabolism, functions, properties, stability
      and/or cellular localization of glycoproteins in cancer cells, resulting in part
      in their uncontrolled growth and aggressive behavior. Therefore glycosylation
      pathways, and the glycosidases and glycosyltransferases of these pathways,
      represent potential innovative modalities for drug development in cancer
      therapies which are just beginning to be explored. This review proposes to
      summarize the published information for glycosidases and their inhibitors in
      cancer.

PMID- 17018004
TI  - In vitro ADME medium/high-throughput screening in drug preclinical development.
AB  - The study of the ADME features of the huge number of new chemical entities (NCEs)
      produced mainly by combinatorial chemistry has become a bottleneck in the drug
      development process. In response the pharmaceutical industry is involved in the
      development of new medium/high-throughput screening capabilities. The aim of this
      paper is to review some of the available in vitro ADME systems adapted to
      screening requirements together with the technological approaches which can be
      linked to medium/high-throughput molecular screening.

PMID- 17018005
TI  - Industrial applications of hyperthermophilic enzymes: a review.
AB  - Over the past two decades, research scientists have been involved in the
      investigation of thermophilic and hyperthermophilic microorganisms owing to the
      unique features of their enzymic systems. Such in-depth investigations are now on
      their way to mastering the cloning and industrial exploitation of a broad variety
      of genes encoding enzymes involved in starch hydrolysis, amino acid biosynthesis,
      protein hydrolysis, etc. In this work, we review the state of the art and future
      perspectives of industrial applications of enzymes from hyperthermophilic and
      extreme thermophilic microorganisms, special attention being paid to the
      biotechnological methods involved in their industrial exploitation.

PMID- 17018006
TI  - A cDNA sequence coding for a glutamic acid-rich protein is differentially
      expressed in cassava storage roots.
AB  - We report the isolation and characterization of a cDNA sequence (Mec1) coding for
      a glutamic acid-rich protein (Pt2L4) from cassava storage roots. Comparative
      sequence analysis showed a high identity of Pt2L4 with cassava protein C54, which
      is expressed in vascular tissues of storage roots. Northern blot analysis showed
      that the Mec1 transcript expression pattern might be related to the maturation of
      the storage parenchyma cells.

PMID- 17018007
TI  - Efficient in vitro refolding and characterization of a new peptide from the
      scorpion Buthotus saulcyi venom produced in Escherichia coli.
AB  - The selective toxicity of depressant scorpion neurotoxins to insects is useful in
      studying the insect sodium channel gating, as well as being relevant to several
      other applications. In order to carry out structure/activity studies, the
      functional expression of such polypeptides is required. In the work reported
      here, the cDNA of a new peptide from the venom of the scorpion Buthotus saulcyi
      was cloned and sequenced. It codes for a 64 residues peptide (BsaulI) with 8
      highly-conserved cysteines. This peptide shares high sequence similarity with
      depressant insect toxins of other scorpion species. Large amounts of insoluble
      BsaulI protein were expressed in Escherichia coli. Purification of this peptide
      was carried out under denaturing conditions. Renaturation was performed by pulsed
      dilution of the denatured BsaulI in the refolding buffer. Production of refolded
      Bsaul1, however, is approximately an order of magnitude higher than that obtained
      with similar scorpion depressant toxins. Intrinsic fluorescence, far-UV circular
      dichroism spectra and biological activity assays indicate that the peptide adopts
      a folded structure.

PMID- 17018008
TI  - Kinetic and thermodynamic properties of an immobilized glucoamylase from a
      mesophilic fungus, Arachniotus citrinus.
AB  - Purified glucoamylase from Arachniotus citrinus was immobilized on polyacrylamide
      gel with 70% yield of immobilization. The immobilization improved the pH optima,
      temperature optima, values of K(m), V(max), and activation energy. Irreversible
      thermal denaturation studies of soluble and immobilized glucoamylase indicated
      that immobilization decreased the entropy and enthalpy of deactivation by
      magnitudes and made the immobilized glucoamylase thermodynamically more stable.

PMID- 17018009
TI  - Inhibition of pancreatic ribonuclease A aggregation by antibodies raised against
      the native enzyme and its N-terminal dodecapeptide.
AB  - Pancreatic ribonuclease A (RNase A) has been shown to aggregate moderately and
      gradually at 65 degrees C. Antibodies raised against the dodecapeptide
      KETAAAKFERQG corresponding to the N-terminal 1-12 amino acid residues of RNase A
      (Npep) as well as native RNase A were effective in lowering RNase A aggregation
      at 65 degrees C. The antiRNase A antibodies were, however, more protective. The
      binding of antiNpep antibodies to the N-terminal region of RNase A may interfere
      with initiation of oligomerization of the enzyme and consequently its
      aggregation. The antiRNase A antibodies were presumably more effective in
      protecting RNase A against aggregation by binding to multiple epitopes of the
      enzyme including the N-terminal region and hence restricting the interaction of
      the monomers.

PMID- 17018010
TI  - The proline-rich domain and the microtubule binding domain of protein tau acting
      as RNA binding domains.
AB  - Neuronal tau, through its proline-rich domain and the microtubule binding domain,
      binds to RNA non-sequence-specifically via electrostatic interaction. This
      binding inhibits the activity of tau. Tau and RNA were also found to co-localize
      in SH-SY5Y cells suggesting that RNA has opportunities to interact with tau in
      cells.

PMID- 17018011
TI  - Web-ware bioinformatical analysis and structure modelling of N-terminus of human
      multisynthetase complex auxiliary component protein p43.
AB  - Human multisynthetase complex auxiliary component, protein p43 is an endothelial
      monocyte-activating polypeptide II precursor. In this study, comprehensive
      sequence analysis of N-terminus has been performed to identify structural
      domains, motifs, sites of post-translation modification and other functionally
      important parameters. The spatial structure model of full-chain protein p43 is
      obtained.

PMID- 17018012
TI  - Key residues involved in Hsp70 regulatory activity and affect of co-chaperones on
      mechanism of action.
AB  - Hsp70 proteins assist refolding of polypeptides in an ATP dependent manner.
      Crystal structure of intact Hsp70 protein has not been determined yet however,
      structures of its two domains were solved separately. Allostery between ATPase
      domain and peptide-binding domain facilitates unfolded substrate processing. To
      elucidate function of key residues and affect of other factors involved in this
      allosteric mechanism, a biochemical study was undertaken.

PMID- 17018013
TI  - Heat shock proteins, substrate specificity and modulation of function.
AB  - Hsp70 is a universally conserved essential protein chaperone. In addition to its
      roles in many cellular process, Hsp70 protects cells from stress by binding
      partially unfolded proteins. Therefore, Hsp70 prevents protein aggregation and
      prion formation. Prions are infectious agents and are responsible for several
      fatal neurodegenerative diseases. Eukaryotic cells have several cytosolic Hsp70
      isoforms, some constitutively expressed (Hsc70s), and others expressed only when
      cells are exposed to stress (Hsp70s). To determine which factors conferred
      functional specificity, we constructed hybrid Hsc/Hsp chaperones. All hybrids
      supported growth except those that contained the ATPase domain derived from
      inducible Hsp70. Thus, regulation of peptide binding by ATP hydrolysis must
      differ significantly between Hsc- and Hsp70 isoforms. In this work, nucleotide
      and peptide binding domain communication of Hsp70 proteins during their
      interaction with nucleotides and peptide substrates were investigated in vitro by
      using hybrid constructs.

PMID- 17018014
TI  - Cytotoxic action in myoblasts and myotubes (C2C12) and enzymatic characterization
      of a new phospholipase A2 isoform (Bj-V) from Bothrops jararacussu venom.
AB  - A new PLA2 Bj-V from Bothrops jararacussu (14039.49 Da determined by MALDI-TOF
      mass spectrometry) was isolated in only one chromatographic step by HPLC ion
      exchange and its purity was confirmed by reverse phase. Amino acid analysis
      showed a high content of hydrophobic and basic amino acids as well as 14 half
      cysteine residues. The N-terminal sequence (DLWQFGQMIL KETGKIPFPY YGAYGCYCGW
      GGRGGKPKDG TDRCCYVHD...) showed a high degree of homology with basic D49 PLA2
      myotoxins from other Bothrops venoms. Bj V showed discrete sigmoidal enzymatic
      behavior, with maximal activity at pH 8.4 and 35-40 degrees C. Full PLA2 activity
      required Ca2+ (10 mM) and there was little catalytic activity in the presence of
      1 mM Ca2+. The addition of Mn2+ or Mg2+ (10 mM) in the presence of low (1 mM)
      Ca2+ slightly increased the enzyme activity, whereas Zn2+ and Cu2+ (10 mM)
      diminished the activity. The substitution of Ca2+ for Mg2+ or Cu2+ also reduced
      the enzymatic activity. Bj V had PLA2 activity and produced cytotoxicity in
      murine C2C12 skeletal muscle myoblasts and myotubes. The isolation of these
      isoforms Bj-IV [1] and Bj-V (described herein) found in a fraction previously
      described as homogeneous shows us the importance of optimization in purification
      techniques in order to better understand their biological behavior.

PMID- 17018015
TI  - Solid-phase synthesis of reactive peptide crosslinker by selective deprotection.
AB  - An effective and simple strategy for preparing peptide crosslinkers is described.
      An MMP-13 degradable peptide QPQGLAK-NH(2) was prepared on the solid-phase using
      Fmoc chemistry. The peptide crosslinker was synthesized on-bead by the coupling
      reaction between acrylic acid and the amine groups of glutamine and lysine
      residues. The synthetic procedure employed the acid-labile Fmoc-Lys (Mtt)-OH and
      base-labile Fmoc-AA-OH derivatives. Selective deprotection, of -Mtt and -Fmoc
      groups on-bead, freed the amine end-groups on glutamine and lysine residues for
      coupling reaction with acrylic acid while maintaining the peptide attached to the
      resin. Subsequent cleavage from the resin yielded a peptide crosslinker with two
      unsaturated acrylate end-groups with high yield and purity. This method can be
      generally employed for the synthesis of a wide range of peptides with one or more
      reactive groups for grafting in the fabrication of biomimetic scaffolds in tissue
      engineering applications.

PMID- 17018016
TI  - Improvement of bacterial cell selectivity of melittin by a single Trp mutation
      with a peptoid residue.
AB  - To design melittin (ME) analogues that are not cytotoxic against mammalian cells
      but which possessing potent antimicrobial activity, we synthesized a ME analogue
      (ME-w) in which the Trp-19 residue of ME was replaced by a Trp-peptoid residue
      (Nhtrp). ME-w exhibited similar antimicrobial activity compared to ME against the
      tested six bacteria and C. albicans. However, it was much less cytotoxic against
      the hRBCs and HeLa and NIH-3T3 cells than ME. Tryptophan fluorescence and CD
      spectra revealed that the Trp-19 --> Nhtrp substitution in ME contributed to a
      much lower helical assembly in an aqueous environment and structural flexibility
      and exterior localization to zwitterionic membrane which modulates its
      selectivity toward bacterial cells.

PMID- 17018017
TI  - High level expression and characterization of the cyclophilin B gene from the
      anaerobic fungus Orpinomyces sp. strain PC-2.
AB  - Cyclophilins are an evolutionarily conserved family of peptidyl-prolyl cis-trans
      isomerases (PPIases). A cyclophilin B (cypB) gene from the anaerobic fungus
      Orpinomyces sp. strain PC-2 was cloned and overexpressed in Escherichia coli. It
      was expressed as an amino-terminal 6 x His-tagged recombinant protein to
      facilitate purification. Highly purified protein (26.5 kDa) was isolated by two
      chromatographic steps involving affinity and gel filtration for biochemical
      studies of the enzyme. The recombinant CypB displayed PPIase activity with a
      k(cat)/K(m) of 8.9 x 10(6) M(-1) s(-1) at 10 degrees C and pH 7.8. It was
      inhibited by cyclosporin A (CsA) with an IC(50) of 23.5 nM, similar to those of
      the native protein and other cyclophilin B enzymes from animals. Genomic DNA
      analysis of cypB revealed that it was present as a single copy in Orpinomyces PC
      2 and contained two introns, indicating it has a eukaryotic origin. It is one of
      the most heavily interrupted genes with intron sequences found in anaerobic
      fungi. The three-dimensional model of Orpinomyces PC-2 CypB was predicted with a
      homology modeling approach using the Swiss-Model Protein Modeling Server and
      three dimensional structure of human CypB as a template. The overall architecture
      of the CypB molecule is very similar to that of human CypB.

PMID- 17018018
TI  - Inputting information about amino acid residues in protein bioinformatics: a case
      study on predicting helical regions with a neural network.
AB  - The best way to introduce information about amino acid residues into calculations
      of protein bioinformatics was examined. That was done for predicting helical
      regions with a neural network. Several fundamental and instructive ways for
      information processing were developed and are described.

PMID- 17018019
TI  - Acidic extracellular proteases from microrganisms of fairly acidic niche.
AB  - The protein population secreted from three wine-contaminant microorganisms was
      studied by two-dimensional electrophoresis and screened for proteases.
      Proteolytic enzymes were electrophoretically purified and their activity, optimum
      pH and temperature determined. The protease of Acetobacter aceti maintained its
      activity over the range of pHs 3.0-5.0, thus being of potential biotechnological
      interest.

PMID- 17018020
TI  - A structural-energetic basis for B-cell epitope prediction.
AB  - Structural-energetic analysis of peptide and protein antigens in the context of
      binding to antibody reveals fundamental differences between the cross-reactions
      of antipeptide antibody with protein and antiprotein antibody with peptide,
      providing a physicochemical basis for B-cell epitope prediction as applied to the
      development of peptide-based vaccines and immunodiagnostics.

PMID- 17018021
TI  - Proteinase K-sensitive disease-associated ovine prion protein revealed by
      conformation-dependent immunoassay.
AB  - PrPSc [abnormal disease-specific conformation of PrP (prion-related protein)]
      accumulates in prion-affected individuals in the form of amorphous aggregates.
      Limited proteolysis of PrPSc results in a protease-resistant core of PrPSc of
      molecular mass of 27-30 kDa (PrP27-30). Aggregated forms of PrP co-purify with
      prion infectivity, although infectivity does not always correlate with the
      presence of PrP27-30. This suggests that discrimination between PrPC (normal
      cellular PrP) and PrPSc by proteolysis may underestimate the repertoire and
      quantity of PrPSc subtypes. We have developed a CDI (conformation-dependent
      immunoassay) utilizing time-resolved fluorescence to study the conformers of
      disease-associated PrP in natural cases of sheep scrapie, without using PK
      (proteinase K) treatment to discriminate between PrPC and PrPSc. The capture
      detector CDI utilizes N-terminal- and C-terminal-specific anti-PrP monoclonal
      antibodies that recognize regions of the prion protein differentially buried or
      exposed depending on the extent of denaturation of the molecule. PrPSc was
      precipitated from scrapie-infected brain stem and cerebellum tissue following
      sarkosyl extraction, with or without the use of sodium phosphotungstic acid, and
      native and denatured PrPSc detected by CDI. PrPSc was detectable in brain tissue
      from homozygous VRQ (V136 R154 Q171) and ARQ (A136 R154 Q171) scrapie-infected
      sheep brains. The highest levels of PrPSc were found in homozygous VRQ scrapie
      infected brains. The quantity of PrPSc was significantly reduced, up to 90% in
      some cases, when samples were treated with PK prior to the CDI. Collectively, our
      results show that the level of PrPSc in brain samples from cases of natural
      scrapie display genotypic differences and that a significant amount of this
      material is PK-sensitive.

PMID- 17018022
TI  - Regulation of mitogen-activated protein kinases by glutamate receptors.
AB  - Glutamate receptors regulate gene expression in neurons by activating
      intracellular signaling cascades that phosphorylate transcription factors within
      the nucleus. The mitogen-activated protein kinase (MAPK) cascade is one of the
      best characterized cascades in this regulatory process. The Ca(2+)-permeable
      ionotropic glutamate receptor, mainly the NMDA receptor subtype, activates MAPKs
      through a biochemical route involving the Ca(2+)-sensitive Ras-guanine nucleotide
      releasing factor, Ca(2+)/calmodulin-dependent protein kinase II, and
      phosphoinositide 3-kinase. The metabotropic glutamate receptor (mGluR), however,
      activates MAPKs primarily through a Ca(2+)-insensitve pathway involving the
      transactivation of receptor tyrosine kinases. The adaptor protein Homer also
      plays a role in this process. As an information superhighway between surface
      glutamate receptors and transcription factors in the nucleus, active MAPKs
      phosphorylate specific transcription factors (Elk-1 and CREB), and thereby
      regulate distinct programs of gene expression. The regulated gene expression
      contributes to the development of multiple forms of synaptic plasticity related
      to long-lasting changes in memory function and addictive properties of drugs of
      abuse. This review, by focusing on new data from recent years, discusses the
      signaling mechanisms by which different types of glutamate receptors activate
      MAPKs, features of each MAPK cascade in regulating gene expression, and the
      importance of glutamate/MAPK-dependent synaptic plasticity in memory and
      addiction.

PMID- 17018023
TI  - Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the
      constitutive activity of central serotonin2C receptors.
AB  - Central serotonin2C receptors (5-HT(2C)Rs) control the mesoaccumbens dopamine
      (DA) pathway. This control involves the constitutive activity (CA) of 5-HT(2C)Rs,
      and is thought to engage regionally distinct populations of 5-HT(2C)Rs, leading
      to opposite functional effects. Here, using in vivo microdialysis in halothane
      anesthetized rats, we investigated the relative contribution of ventral tegmental
      area (VTA) and nucleus accumbens shell (NAc) 5-HT(2C)Rs in the phasic/tonic
      control of accumbal DA release, to specifically identify the nature
      (inhibition/excitation) of the control, and the role of the 5-HT(2C)R CA. Intra
      VTA injections of the selective 5-HT(2C)R antagonists SB 242084 and/or SB 243213
      (0.1-0.5 microg/0.2 microL) prevented the decrease in accumbal DA outflow induced
      by the 5-HT(2C)R agonist Ro 60-0175 (3 mg/kg, i.p), but did not affect the
      increase in DA outflow induced by the 5-HT(2C)R inverse agonist SB 206553 (5
      mg/kg, i.p). Intra-NAc infusions of SB 242084 (0.1-1 microM) blocked Ro 60-0175-
      and SB 206553-induced changes of DA outflow. Intra-NAc, but not intra-VTA
      administration of SB 206553 increased basal DA outflow. These findings
      demonstrate that both VTA and NAc 5-HT(2C)Rs participate in the inhibitory
      control exerted by 5-HT(2C)Rs on accumbal DA release, and that the NAc shell may
      represent a primary action site for the CA of 5-HT(2C)Rs.

PMID- 17018024
TI  - Extracellular S-nitrosoglutathione, but not S-nitrosocysteine or N(2)O(3),
      mediates protein S-nitrosation in rat spinal cord slices.
AB  - There is evidence that protein S-nitrosothiols (PrSNOs) accumulate in
      inflammatory demyelinating disorders like multiple sclerosis and experimental
      allergic encephalomyelitis. However, very little is known regarding the mechanism
      by which PrSNOs are formed in target cells. The present study compares the
      ability of potential intercellular mediators of nitrosative damage including S
      nitrosoglutathione (GSNO), S-nitrosocysteine and N(2)O(3) to induce protein S
      nitros(yl)ation in the spinal cord, a CNS region that is commonly affected in
      multiple sclerosis and experimental allergic encephalomyelitis. The results
      clearly demonstrate that while all three NO-donors cause S-nitrosation of
      proteins in cell-free systems, only GSNO is a viable S-nitrosating agent in rat
      spinal cord slices. Generation of PrSNOs with GSNO occurs by S-transnitrosation
      as the process was not inhibited by either the NO-scavenger rutin or the N(2)O(3)
      scavenger azide. Contrary to other cell types, nerve cells incorporate intact
      GSNO and neither functional l-amino acid transporters nor cell-surface thiols are
      required. We also found that there is a restricted number of proteins available
      for S-nitrosation, even at high, non-physiological concentrations of GSNO. These
      proteins are highly concentrated in mitochondria and mitochondria-rich
      subcellular compartments. This study is relevant to those CNS disorders
      characterized by excessive nitric oxide production.

PMID- 17018025
TI  - Protective effects of an anti-inflammatory cytokine, interleukin-4, on motoneuron
      toxicity induced by activated microglia.
AB  - Microglia-mediated cytotoxicity has been implicated in models of
      neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's
      disease and Alzheimer's disease, but few studies have documented how
      neuroprotective signals might mitigate such cytotoxicity. To explore the
      neuroprotective mechanism of anti-inflammatory cytokines, we applied interleukin
      4 (IL-4) to primary microglial cultures activated by lipopolysaccharide as well
      as to activated microglia cocultured with primary motoneurons. lipopolysaccharide
      increased nitric oxide and superoxide (O(2) (.-)) and decreased insulin-like
      growth factor-1 (IGF-1) release from microglial cultures, and induced motoneuron
      injury in microglia-motoneuron cocultures. However, lipopolysaccharide had
      minimal effects on isolated motoneuron cultures. IL-4 interaction with microglial
      IL-4 receptors suppressed and nitric oxide release, and lessened
      lipopolysaccharide-induced microglia-mediated motoneuron injury. The extent of
      nitric oxide suppression correlated directly with the extent of motoneuron
      survival. Although IL-4 enhanced release of free IGF-1 from microglia in the
      absence of lipopolysaccharide, it did not enhance free IGF-1 release in the
      presence of lipopolysaccharide. These data suggest that IL-4 may provide a
      significant immunomodulatory signal which can protect against microglia-mediated
      neurotoxicity by suppressing the production and release of free radicals.

PMID- 17018026
TI  - Identification and characterization of PEBP as a calpain substrate.
AB  - Calpains are calcium- and thiol-dependent proteases whose dysregulation has been
      implicated in a number of diseases and conditions such as cardiovascular
      dysfunction, ischemic stroke, and Alzheimer's disease (AD). While the effects of
      calpain activity are evident, the precise mechanism(s) by which dysregulated
      calpain activity results in cellular degeneration are less clear. In order to
      determine the impact of calpain activity, there is a need to identify the range
      of specific calpain substrates. Using an in vitro proteomics approach we
      confirmed that phosphatidylethanolamine-binding protein (PEBP) as a novel in
      vitro and in situ calpain substrate. We also observed PEBP proteolysis in a model
      of brain injury in which calpain is clearly activated. In addition, with evidence
      of calpain dysregulation in AD, we quantitated protein levels of PEBP in
      postmortem brain samples from the hippocampus of AD and age-matched controls and
      found that PEBP levels were approximately 20% greater in AD. Finally, with
      previous evidence that PEBP may act as a serine protease inhibitor, we tested
      PEBP as an inhibitor of the proteasome and found that PEBP inhibited the
      chymostrypsin-like activity of the proteasome by approximately 30%. Together
      these data identify PEBP as a potential in vivo calpain substrate and indicate
      that increased PEBP levels may contribute to impaired proteasome function.

PMID- 17018027
TI  - Down-regulation of WNK1 protein kinase in neural progenitor cells suppresses cell
      proliferation and migration.
AB  - WNK1, a Ser/Thr protein kinase, is widely expressed in many tissues. Its
      biological functions are largely unknown. Disruption of the WNK1 gene in mice
      leads to embryonic lethality at day 13, implicating a critical role of WNK1 in
      embryonic development. To investigate this potential function, we used antisense
      strategy to knock down the expression of WNK1 in a mouse neural progenitor cell
      line, C17.2. Down-regulation of WNK1 in C17.2 cells greatly reduced cell growth.
      Addition of epidermal growth factor (EGF), a mitogen for C17.2 cells, had no
      effect on growth. The WNK1-knockdown cells showed a flat and rounded morphology,
      characteristic of the immature and non-differentiated phenotype of the progenitor
      cells; this was further demonstrated by immunostaining for the progenitor and
      neuronal markers. Migration of the WNK1-knockdown C17.2 cells was reduced as
      tested in culture dishes or Matrigel-covered chambers. Moreover, activation of
      extracellular signal-regulated kinase (ERK1)/2 and ERK5 by EGF in the WNK1
      knockdown cells was suppressed. These results demonstrate a novel function of
      WNK1 in proliferation, migration, and differentiation of neural progenitor cells,
      likely by mechanisms involving activation of the mitogen-activated protein (MAP)
      kinase ERK1/2 and/or ERK5 pathways.

PMID- 17018028
TI  - TRPV1b overexpression negatively regulates TRPV1 responsiveness to capsaicin,
      heat and low pH in HEK293 cells.
AB  - Transient receptor potential channel type V (TRPV) 1 is a non-selective cation
      channel that can be activated by capsaicin, endogenous vanilloids, heat and
      protons. The human TRPV1 splice variant, TRPV1b, lacking exon 7, was cloned from
      human dorsal root ganglia (DRG) RNA. The expression profile and relative
      abundance of TRPV1b and TRPV1 in 35 different human tissues were determined by
      quantitative RT-PCR using isoform-specific probes. TRPV1b was most abundant in
      fetal brain, adult cerebellum and DRG. Functional studies using
      electrophysiological techniques showed that recombinant TRPV1b was not activated
      by capsaicin (1 microM), protons (pH 5.0) or heat (50 degrees C). However,
      recombinant TRPV1b did form multimeric complexes and was detected on the plasma
      membrane of cells, demonstrating that the lack of channel function was not due to
      defects in complex formation or cell surface expression. These results
      demonstrate that exon 7, which encodes the third ankyrin domain and 44 amino
      acids thereafter, is required for normal channel function of human TRPV1.
      Moreover, when co-expressed with TRPV1, TRPV1b formed complexes with TRPV1, and
      inhibited TRPV1 channel function in response to capsaicin, acidic pH, heat and
      endogenous vanilloids, dose-dependently. Taken together, these data support the
      hypothesis that TRPV1b is a naturally existing inhibitory modulator of TRPV1.

PMID- 17018029
TI  - Anion exchanger 2 mediates the action of arsenic trioxide.
AB  - Anion exchanger 2 (AE2) mediates the exchange of C1-/HCO3- across the plasma
      membrane and plays a role in the regulation of intracellular pH. The present
      study showed that AE2 protein expression was upregulated immediately after
      exposure to either low (0.5 micromol/l) or high (1 and 2 micromol/l)
      concentrations of arsenic trioxide. This suggests that arsenic trioxide may act
      via regulation of intracellular pH. Changing the culture pH in NB4 cells
      modulated the degradation of promyelocytic leukaemia-retinoic acid receptor-alpha
      (PML-RARalpha), PML and RARalpha, which supported this hypothesis. DIDS (4,4'
      diisothiocyanodihydrostilbene-2,2'-disulphonic acid) inhibited AE2 function,
      preventing the arsenic trioxide-induced degradation of RARalpha and low
      concentration showed synergistic effects on the expression of CD11c, which is
      related with cell differentiation. In addition, DIDS rescued the cells from 1
      micromol/l arsenic trioxide-induced apoptosis. In conclusion, AE2 mediated the
      action of arsenic trioxide via regulation of intracellular pH and a novel pathway
      for the mechanism of action of arsenic trioxide is reported.

PMID- 17018030
TI  - Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte
      colony-stimulating factor (G-CSF): impact of age, sex, donor weight and type of G
      CSF used.
AB  - Mobilised peripheral blood is now the main source of stem cells collected from
      normal donors. We report our experience of mobilising and collecting 400 normal
      healthy donors using standardised procedures and techniques. Target recipient
      doses were reached with one aphaeresis in 63% of donors and with two aphereses in
      81% of donors. Approximately 2% of donors yielded such low progenitor values that
      they were termed 'poor mobilisers'. There were minor effects of donor age, weight
      and sex and where possible, larger male donors under the age of 55 years should
      be selected. Two forms of granulocyte colony-stimulating factor (G-CSF) were used
      at the same dose and no significant difference was seen in the yield of CD34+
      cells collected/l of blood processed. However, a greater number of granulocyte
      macrophage colony-forming cells were harvested using lenograstim (glycosylated G
      CSF) compared with filgrastim (non-glycosylated G-CSF; P = 0.002). CD34+ cell
      yields were also measured halfway through the aphaeresis procedure. This was
      found to be highly predictive of final yield and facilitated distribution of the
      stem cell product to other centres. The observation that CD34+ yields did not
      decline in the second half compared with the first half of aphaeresis suggests
      that the circulating cell numbers are not static.

PMID- 17018031
TI  - Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination.
AB  - The Spo11 protein is a eukaryotic homologue of the archaeal DNA topoisomerase VIA
      subunit (topo VIA). In archaea it is involved, together with its B subunit (topo
      VIB), in DNA replication. However, most eukaryotes, including yeasts, insects and
      vertebrates, instead have a single gene for Spo11/topo VIA and no homologues for
      topo VIB. In these organisms, Spo11 mediates DNA double-strand breaks that
      initiate meiotic recombination. Many plant species, in contrast to other
      eukaryotes, have three homologues for Spo11/topo VIA and one for topo VIB. The
      homologues in Arabidopsis, AtSPO11-1, AtSPO11-2 and AtSPO11-3, all share 20-30%
      sequence similarity with other Spo11/topo VIA proteins, but their functional
      relationship during meiosis or other processes is not well understood. Previous
      genetic evidence suggests that AtSPO11-1 is a true orthologue of Spo11 in other
      eukaryotes and is required for meiotic recombination, whereas AtSPO11-3 is
      involved in DNA endo-reduplication as a part of the topo VI complex. In this
      study, we show that plants homozygous for atspo11-2 exhibit a severe sterility
      phenotype. Both male and female meiosis are severely disrupted in the atspo11-2
      mutant, and this is associated with severe defects in synapsis during the first
      meiotic division and reduced meiotic recombination. Further genetic analysis
      revealed that AtSPO11-1 and AtSPO11-2 genetically interact, i.e. plants
      heterozygous for both atspo11-1 and atspo11-2 are also sterile, suggesting that
      AtSPO11-1 and AtSPO11-2 have largely overlapping functions. Thus, the three
      Arabidopsis Spo11 homologues appear to function in two discrete processes, i.e.
      AtSPO11-1 and AtSPO11-2 in meiotic recombination and AtSPO11-3 in DNA
      replication.

PMID- 17018032
TI  - Salicylic acid-mediated and RNA-silencing defense mechanisms cooperate in the
      restriction of systemic spread of plum pox virus in tobacco.
AB  - Plum pox virus (PPV) is able to replicate in inoculated leaves of Nicotiana
      tabacum, but is defective in systemic movement in this host. However, PPV
      produces a systemic infection in transgenic tobacco expressing the silencing
      suppressor P1/HC-Pro from tobacco etch virus (TEV). In this work we show that PPV
      is able to move to upper non-inoculated leaves of tobacco plants expressing
      bacterial salicylate hydroxylase (NahG) that degrades salicylic acid (SA).
      Replication and accumulation of PPV is higher in the locally infected leaves of
      plants deficient in SA or expressing TEV P1/HC-Pro silencing suppressor.
      Accumulation of viral derived small RNAs was reduced in the NahG transgenic
      plants, suggesting that SA might act as an enhancer of the RNA-silencing
      antiviral defense in tobacco. Besides, expression of SA-mediated defense
      transcripts, such as those of pathogenesis-related (PR) proteins PR-1 and PR-2 or
      alternative oxidase-1, as well as that of the putative RNA-dependent RNA
      polymerase NtRDR1, is induced in response to PPV infection, and the expression
      patterns of these defense transcripts are altered in the TEV P1/HC-Pro transgenic
      plants. Long-distance movement of PPV is highly enhanced in NahG x P1/HC-Pro
      double-transgenic plants and systemic symptoms in these plants reveal that the
      expression of an RNA-silencing suppressor and the lack of SA produce additive but
      distinct effects. Our results suggest that SA might act as an enhancer of the RNA
      silencing antiviral defense in tobacco, and that silencing suppressors, such as
      P1/HC-Pro, also alter the SA-mediated defense. Both an RNA-silencing and an SA
      mediated defense mechanism could act together to limit PPV infection.

PMID- 17018033
TI  - Developing fructan-synthesizing capability in a plant invertase via mutations in
      the sucrose-binding box.
AB  - Fructans are fructose polymers that are synthesized from sucrose by
      fructosyltransferases. Fructosyltransferases are present in unrelated plant
      families suggesting a polyphyletic origin for their transglycosylation activity.
      Based on sequence comparisons and enzymatic properties, fructosyltransferases are
      proposed to have evolved from vacuolar invertases. Between 1% and 5% of the total
      activity of vacuolar invertase is transglycosylating activity. We investigated
      the nature of the changes that can convert a hydrolysing invertase into a
      transglycosylating enzyme. Remarkably, replacing 33 amino acids (amino acids 143
      175) corresponding to the N-terminus of the mature onion vacuolar invertase with
      the corresponding region of onion fructan:fructan 6G-fructosyltransferase (6G
      FFT) led to a shift in activity from hydrolysis of sucrose towards
      transglycosylation between two sucrose molecules. The substituted N-terminal
      region contains the sucrose-binding box that harbours the nucleophile involved in
      sucrose hydrolysis (Asp164). Subsequent research into the individual amino acids
      responsible for the enhanced transglycosylation activity revealed that mutations
      in amino acids Trp161 and Asn166, can give rise to a shift towards polymerase
      activity. Changing the amino acid at either of these positions in the sucrose
      binding box increases the transglycosylation capacity of invertases two- to
      threefold compared to wild type. Combining the two mutations had an additive
      effect on transglycosylation ability, resulting in an approximately fourfold
      enhancement. The mutations generated correspond with natural variation present in
      the sucrose-binding boxes of vacuolar invertases and fructosyltransferases. These
      relatively small changes that increase the transglycosylation capacity of
      invertases might explain the polyphyletic origin of the fructan accumulation
      trait.

PMID- 17018034
TI  - The C2 domain protein BAP1 negatively regulates defense responses in Arabidopsis.
AB  - The Arabidopsis BAP1 gene encodes a small protein with a C2-like domain. Here we
      show that the BAP1 protein is capable of binding to phospholipids in a calcium
      dependent manner and is associated with membranes in vivo. We identify multiple
      roles of BAP1 in negatively regulating defense responses and cell death in
      Arabidopsis thaliana. The loss of BAP1 function confers an enhanced disease
      resistance to virulent bacterial and oomycete pathogens. The enhanced resistance
      is mediated by salicylic acid, PAD4 and a disease resistance gene SNC1. BAP1 is
      also involved in the control of cell death, which is suggested by an altered
      hypersensitive response to an avirulent bacterial pathogen in the bap1 loss-of
      function mutant. BAP1 overexpression leads to an enhanced susceptibility to a
      virulent oomycete, suggesting a role for BAP1 in basal defense response.
      Furthermore, the BAP1 protein probably functions together with an evolutionarily
      conserved C2 domain protein BON1/CPN1 to negatively regulate defense responses in
      plants.

PMID- 17018035
TI  - Endogenous isoflavones are essential for the establishment of symbiosis between
      soybean and Bradyrhizobium japonicum.
AB  - Legume iso/flavonoids have been implicated in the nodulation process, but
      questions remain as to their specific role(s), and no unequivocal evidence exists
      showing that these compounds are essential for nodulation. Two hypotheses suggest
      that the primary role of iso/flavonoids is their ability to induce rhizobial nod
      gene expression and/or their ability to modulate internal root auxin
      concentrations. The present work provides direct, genetic evidence that
      isoflavones are essential for nodulation of soybean roots because of their
      ability to induce the nodulation genes of Bradyrhizobium japonicum. Expression of
      isoflavone synthase (IFS), a key enzyme in the biosynthesis of isoflavones, is
      specifically induced by B. japonicum. When IFS was silenced using RNA
      interference in soybean hairy root composite plants, these plants had severely
      reduced nodulation. Surprisingly, pre-treatment of B. japonicum or exogenous
      application to the root system of either of the major soybean isoflavones,
      daidzein or genistein, failed to restore normal nodulation. Silencing of chalcone
      reductase led to very low levels of daidzein and increased levels of genistein,
      but did not affect nodulation, suggesting that the endogenous production of
      genistein was sufficient to support nodulation. Consistent with a role for
      isoflavones as endogenous regulators of auxin transport in soybean roots,
      silencing of IFS resulted in altered auxin-inducible gene expression and auxin
      transport. However, use of a genistein-hypersensitive B. japonicum strain or
      purified B. japonicum Nod signals rescued normal nodulation in IFS-silenced
      roots, indicating that the ability of isoflavones to modulate auxin transport is
      not essential to nodulation.

PMID- 17018036
TI  - Plastidial phosphorylase is required for normal starch synthesis in Chlamydomonas
      reinhardtii.
AB  - Among the three distinct starch phosphorylase activities detected in
      Chlamydomonas reinhardtii, two distinct plastidial enzymes (PhoA and PhoB) are
      documented while a single extraplastidial form (PhoC) displays a higher affinity
      for glycogen as in vascular plants. The two plastidial phosphorylases are shown
      to function as homodimers containing two 91-kDa (PhoA) subunits and two 110-kDa
      (PhoB) subunits. Both lack the typical 80-amino-acid insertion found in the
      higher plant plastidial forms. PhoB is exquisitely sensitive to inhibition by ADP
      glucose and has a low affinity for malto-oligosaccharides. PhoA is more similar
      to the higher plant plastidial phosphorylases: it is moderately sensitive to ADP
      glucose inhibition and has a high affinity for unbranched malto-oligosaccharides.
      Molecular analysis establishes that STA4 encodes PhoB. Chlamydomonas reinhardtii
      strains carrying mutations at the STA4 locus display a significant decrease in
      amounts of starch during storage that correlates with the accumulation of
      abnormally shaped granules containing a modified amylopectin structure and a high
      amylose content. The wild-type phenotype could be rescued by reintroduction of
      the cloned wild-type genomic DNA, thereby demonstrating the involvement of
      phosphorylase in storage starch synthesis.

PMID- 17018037
TI  - Lymphatic tracing and T cell responses following oral vaccination with live
      Mycobacterium bovis (BCG).
AB  - Oral vaccination of mice with lipid-encapsulated Mycobacterium bovis bacille
      Calmette-Guerin (BCG) expands a subset of interferon-gamma (IFN-gamma)-secreting
      T cells and mediates protection against aerosol mycobacterial challenge. We have
      traced the movement of the live vaccine through the regional lymphatics of mice
      and monitored the resultant immune response. Six hours after oral vaccination BCG
      was detected in low numbers systemically and in draining lymphatic tissue.
      However, after 48 h, BCG was predominantly associated with alimentary tract
      lymphatic tissues, such as the cervical and mesenteric lymph nodes and Peyer's
      patches. Lymphocytes that produced IFN-gamma in response to PPD-B or BCG-pulsed
      dendritic cells predominated in the spleen and were almost exclusively CD4(+),
      CD44(+) and CD62L(-), thus resembling an effector memory T cell population.
      Despite the fact that an oral route was used for immunization, splenic IFN-gamma
      secreting T cells in vaccinated mice did not express the mucosal homing antigens
      alpha(4)beta(7) integrin or alphaIEL (CD103). However, a proportion of BCG
      specific CD4(+) T cells expressed the CD29 integrin (beta(1)) chain, potentially
      involved in lung homing function. Thus, oral priming with M. bovis BCG appears to
      induce a subset of spleen-resident CD4(+) T cells with the potential to provide
      protective immunity in the lung.

PMID- 17018038
TI  - Developmental coordination disorder: Current issues.

PMID- 17018039
TI  - The development and standardization of the Children Activity Scales (ChAS-P/T)
      for the early identification of children with Developmental Coordination
      Disorders.
AB  - BACKGROUND: Previous studies have emphasized the importance of early
      identification of children with Developmental Coordination Disorder (DCD) to
      prevent the development of secondary academic, emotional and social
      manifestations of the disorder. The aim of this study was to develop a valid
      parent and teacher questionnaire--the Children Activity Scales for parents (ChAS
      P) and for teachers (ChAS-T)--to identify children aged 4-8 years at risk for DCD
      and to examine the reliability and validity of these questionnaires. METHODS: The
      questionnaires' content and face validity were established, and then cut-off
      scores were determined based on responses of 355 teachers and 216 parents.
      Internal consistencies were also calculated. Factor analyses were performed, and
      construct validity was determined by examining the questionnaires' ability to
      discriminate between 30 children aged 5-6.5 years diagnosed with DCD and 30
      typically developing children. Concurrent validity was examined by comparing
      questionnaire scores with those of the Movement Assessment Battery for Children
      (M-ABC). RESULTS: High values were obtained for internal consistency (0.96-0.94)
      for the ChAS-T and the ChAS-P respectively. Factor analysis revealed four
      distinct factors within the ChAS-P and three within the ChAS-T, reinforcing the
      theoretical validity of the items selected and appropriateness for identifying
      DCD. Construct validity was indicated by finding significant differences between
      the groups' scores on the ChAS-T and the ChAS-P. Significant correlations between
      the children's scores on the questionnaires and those of the M-ABC confirmed
      their concurrent validity. CONCLUSIONS: Initial results suggest that the ChAS-T
      and Chas-P are reliable tools to identify children at risk for DCD.

PMID- 17018040
TI  - Motor, visual and egocentric transformations in children with Developmental
      Coordination Disorder.
AB  - AIM: This study aimed to test the internal modelling deficit (IMD) hypothesis
      using the mental rotation paradigm. BACKGROUND: According to the IMD hypothesis,
      children with Developmental Coordination Disorder (DCD) have an impaired ability
      to internally represent action. Thirty-six children (18 DCD) completed four
      tasks: two versions of a single-hand rotation task (with and without explicit
      imagery instructions), a whole-body imagery task and an alphanumeric rotation
      task. RESULTS: There was partial support for the hypothesis that children with
      DCD would display an atypical pattern of performance on the hand rotation task,
      requiring implicit use of motor imagery. Overall, there were no significant
      differences between the DCD and control groups when the hand task was completed
      without explicit instructions, on either response time or accuracy. However, when
      imagery instructions were introduced, the controls were significantly more
      accurate than the DCD group, indicating that children with DCD were unable to
      benefit from explicit cuing. As predicted, the controls were also significantly
      more accurate than the DCD group on the whole-body task, with the accuracy of the
      DCD group barely rising above chance. Finally, and as expected, there was no
      difference between the groups on the alphanumeric task, a measure of visual (or
      object-related) imagery. CONCLUSIONS: The inability of the DCD group to utilize
      specific motor imagery instructions and to perform egocentric transformations
      lends some support to the IMD hypothesis. Future work needs to address the
      question of whether the IMD itself is subgroup-specific.

PMID- 17018041
TI  - An EEG study of mental rotation-related negativity in children with Developmental
      Coordination Disorder.

PMID- 17018042
TI  - Problems in the coupling of eye and hand in the sequential movements of children
      with Developmental Coordination Disorder.
AB  - BACKGROUND: Shifting gaze and attention ahead of the hand is a natural component
      in the performance of skilled manual actions. Very few studies have examined the
      precise co-ordination between the eye and hand in children with Developmental
      Coordination Disorder (DCD). METHODS: This study directly assessed the maturity
      of eye-hand co-ordination in children with DCD. A double-step pointing task was
      used to investigate the coupling of the eye and hand in 7-year-old children with
      and without DCD. Sequential targets were presented on a computer screen, and eye
      and hand movements were recorded simultaneously. RESULTS: There were no
      differences between typically developing (TD) and DCD groups when completing fast
      single-target tasks. There were very few differences in the completion of the
      first movement in the double-step tasks, but differences did occur during the
      second sequential movement. One factor appeared to be the propensity for the DCD
      children to delay their hand movement until some period after the eye had landed
      on the target. This resulted in a marked increase in eye-hand lead during the
      second movement, disrupting the close coupling and leading to a slower and less
      accurate hand movement among children with DCD. CONCLUSIONS: In contrast to
      skilled adults, both groups of children preferred to foveate the target prior to
      initiating a hand movement if time allowed. The TD children, however, were more
      able to reduce this foveation period and shift towards a feedforward mode of
      control for hand movements. The children with DCD persevered with a look-then
      move strategy, which led to an increase in error. For the group of DCD children
      in this study, there was no evidence of a problem in speed or accuracy of simple
      movements, but there was a difficulty in concatenating the sequential shifts of
      gaze and hand required for the completion of everyday tasks or typical assessment
      items.

PMID- 17018043
TI  - Perception-action coupling in children with and without DCD: Frequency locking
      between task-relevant auditory signals and motor responses in a dual-motor task.
AB  - BACKGROUND: The current research examines the relationship between perceptual and
      motor processes, known as perception-action or sensorimotor coupling, and the
      potential differences in perception-action coupling among children with and
      without Developmental Coordination Disorder (DCD) and adults in a gross-motor co
      ordination task (clapping while marching) when a task-relevant driving sensory
      signal is present. METHODS: Ten children with DCD (7.32 + 0.23 years), eight
      typically developing (TD) children who were age-, gender- and racially/ethnically
      matched (6.91 + 0.24 years) and 10 college-aged adults were participants in this
      study. Participants clapped and marched to an auditory beat at four different
      frequencies: 0.8, 1.2,1.6 and 2.0 Hz. The relative timing measures of mean
      relative phase (MRP) and variability of relative phase (VRP) were calculated and
      compared using 3 (group) x 4 (frequency) x 2 (limb) anovas. Qualitatively,
      participants were assessed for the presence of absolute coupling (100% + 15%
      MRP). RESULTS: Statistically significant differences in MRP occurred for
      coupling, frequency and group, and post hoc analysis indicated that the adult
      group differed from both the DCD and TD groups, who did not differ from each
      other. In VRP, there were significant main effects for coupling and group, and a
      significant interaction between group and frequency, with post hoc analysis
      indicating the DCD group to be different from the TD and adult groups.
      Qualitatively, both the adult and TD groups increased in the number of
      participants who adopt absolute coupling as frequency increases. In contrast, the
      DCD participants adopt this absolute coupling far less frequently overall; in
      fact, the number of participants adopting this pattern decreases as frequency
      increases. CONCLUSIONS: These results indicate that children with DCD have
      difficulties with both the co-ordination and the control of their perception
      action coupling for this particular task.

PMID- 17018044
TI  - Rhythmic coordination of hand and foot in children with Developmental
      Coordination Disorder.
AB  - BACKGROUND: Children with Developmental Coordination Disorder (DCD) have
      difficulties producing stable rhythmic bimanual coordination patterns in
      comparison with age-related peers. Rhythmic coordination of non-homologous limbs
      (e.g. hand and foot) is even more difficult to perform because of mechanical
      differences between the limbs. The aim of the present study is to investigate the
      stability of hand-foot coordination patterns of children with DCD. METHODS: Ten
      children with DCD (mean age 7.0 years, SD 1.1 years) and 16 control children
      (mean age 7.4 years, SD 1.3 years) participated in the study. They were asked to
      perform in-phase or anti-phase tapping movements in three different interlimb
      coordination combinations: (1) hand-hand (homologous), (2) hand-foot same body
      side (ipsilateral), and (3) hand-foot different body side (contralateral).
      Coordination stability was measured by the variability of the relative phase
      between the limbs under a 'steady state' (preferred) frequency condition, and by
      the critical frequency (i.e. the point at which loss of pattern stability was
      observed) in a condition in which the movement frequency was 'scaled' up (only
      anti-phase tapping). RESULTS: Coordination patterns of children in the DCD group
      were less stable in all three limb combinations compared with controls. Further,
      hand-foot coordination patterns were less stable than hand-hand coordination
      patterns. With regard to hand-foot coordination, ipsilateral patterns were
      equally stable compared with contralateral patterns in the in-phase task, but
      less stable in the anti-phase task. No differential effects were found between
      the DCD and control groups across the different limb combinations, except for
      steady-state anti-phase coordination in the ipsilateral limb condition. This
      effect was due to a relatively good performance of the control children in this
      condition in comparison with the other limb combination conditions. CONCLUSIONS:
      Children with DCD have difficulties producing stable rhythmic hand-foot
      coordination patterns compared with control children.

PMID- 17018045
TI  - Children with Developmental Coordination Disorder respond similarly to age
      matched controls in both speed and accuracy if goal-directed movements are made
      across the midline.
AB  - BACKGROUND: The conventional view among many clinicians is that crossing the
      midline in children with Developmental Coordination Disorder (DCD) results in
      degradation of their performance. However, no kinematic data yet exist to support
      this view. We therefore tested this assumption in an experimental setting.
      METHODS: A group of age- and gender-matched children with DCD (n = 48) and a
      group of typically developing children (n = 48) were compared while performing
      goal-directed movements with a pen on a XY-tablet. We examined whether speed or
      accuracy changed if the goal-directed movements were made towards targets
      positioned either at the midline, the contralateral (crossed) side or the
      ipsilateral (uncrossed) side of the body midline. RESULTS: Our results showed
      that movements in the contralateral workspace were less accurate for both groups
      of children in the tested age range (6-11 years). The movements made towards the
      targets in the midline were the fastest, and the pen pressure for movements in
      the ipsilateral space was the highest. However, these effects were similar for
      children with and without DCD. As expected, children with DCD made more errors,
      were slower and pressed more erratically on their pen, but this difference was
      irrespective of the position of their hand in the workspace. CONCLUSION: Crossing
      the midline in children with DCD for small amplitude movements (2.5 cm), as
      tested in this study, does not result in increased degradation of the goal
      directed movements compared with their typically developing peers. This implies
      that, contrary to expectation, there is no evidence for a preferential deficit in
      DCD in brain structures involved in making movements in the contralateral
      workspace.

PMID- 17018046
TI  - Visual contribution to walking in children with Developmental Coordination
      Disorder.
AB  - BACKGROUND: The motor co-ordination problems of children with Developmental
      Coordination Disorder (DCD) have been frequently associated with poor
      visuospatial processing. In order to extend these findings mainly based on fine
      motor experiments, the present study investigates the contribution of vision to
      the control of walking in children with DCD. METHODS: Children with DCD (n = 12)
      walked at their preferred speed on a straight, firm and uncluttered walkway in a
      condition with normal lighting and in a dark condition. Spatiotemporal gait
      variables were assessed by means of a three-dimensional ProReflex camera system
      and compared with the gait pattern of matched, typically developing (TD) children
      (n = 12). RESULTS: In normal lighting, the gait pattern of both groups was
      similar, with the exception of subtle differences in the temporal phasing,
      showing a slightly longer support phase in the children with DCD. In the dark,
      step frequency and step length were decreased in the children with DCD, resulting
      in a significantly slower walking velocity. In addition, the medio-lateral
      excursion of the centre of mass tended to increase in this group. In the TD
      children, adaptations to the spatiotemporal pattern remained absent. CONCLUSIONS:
      These results suggest that children with DCD are more dependent on global visual
      flow information than TD children for the maintenance of balance and the control
      of velocity during walking. This increased dependency on visual control might be
      associated with a poorly developed internal sensorimotor model.

PMID- 17018047
TI  - Comorbidity, co-occurrence, continuum: What's in a name?
AB  - BACKGROUND: Comorbidity, co-occurrence and continuum are three terms used when
      referring to developmental problems such as Developmental Coordination Disorder
      (DCD), but they can be confusing and misleading. Further, the terms can be
      upsetting to parents, and are not always helpful in guiding the selection of
      clinical interventions. GOALS: The main purpose of this paper is to question some
      of the terminology we employ when referring to DCD and other developmental
      problems. A secondary purpose is to discuss some of the conceptual frameworks
      that have been proposed that attempt to address the issue of the
      interrelationships among developmental problems. APPROACH: The terminology is
      examined by first referring to the basic dictionary definitions. Second, data we
      have published that relate to the issues of co-occurrence and continuum are
      reviewed in light of the terminology questions. Finally, we review some
      alternative conceptual frameworks which more accurately describe the
      relationships among developmental problems. CONCLUSION: The term 'comorbidity'
      has limited relevance to developmental problems, and its use is questionable. In
      contrast, co-occurrence and continuum are more useful terms to use in regard to
      developmental problems. Concepts such as atypical brain development and minor
      neurological dysfunction provide some possible explanations for the increased
      levels of co-occurrence of developmental disorders in children who are more
      severely affected.

PMID- 17018048
TI  - Comorbidity of DCD and SLI: Significance of epileptiform activity during sleep.
AB  - BACKGROUND: In children affected by specific language impairment (SLI), many
      authors have investigated a link between language and epileptiform discharges
      during sleep resembling the focal sharp waves typical of benign epilepsy with
      centro-temporal spikes (BECTS), the so-called rolandic spikes. On the other hand,
      the same electroencephalographic trait occurs in more than 50% of children
      affected by learning or behavioural disabilities without seizures, supporting the
      hypothesis of a common genetic disposition. The biological background of
      Developmental Coordination Disorder (DCD) is currently unknown, but a genetic
      liability may be assumed. The aims of our study were first to estimate the
      prevalence of sleep-related epileptiform discharges in children affected by DCD
      and second to investigate the occurrence of DCD in a population of children
      affected by BECTS. METHODS: We selected a group of eight children with severe
      DCD. In this group, the presence of epileptiform activity was investigated. We
      also searched for DCD among a group of 13 children affected by BECTS. RESULTS: We
      found rolandic spikes in more than 70% of the children with severe DCD and severe
      DCD in more than 30% of the children with BECTS. CONCLUSIONS: In children with
      severe DCD other disabilities are frequently associated. In these children,
      epileptiform activity during sleep is very frequently found and in our opinion,
      this represents a hallmark of 'Hereditary Impairment of Brain Maturation', a term
      only partially resembling 'Atypical Brain Development'.

PMID- 17018049
TI  - A pilot study of psychopathology in Developmental Coordination Disorder.
AB  - BACKGROUND: This paper explores the prevalence of emotional and behavioural
      disorders in children referred to a Community Paediatric Occupational Therapy
      service for assessment and treatment of problems with development of motor
      skills. METHODS: Parents of 47 children from a clinical sample of children who
      had been identified with Developmental Coordination Disorder (DCD) returned the
      Strengths and Difficulties Questionnaire (SDQ)--a brief measure of the pro-social
      behaviour and psychopathology that can be completed by parents, teachers or
      youths. RESULTS: Significant emotional and behavioural problems were reported by
      29 parents (62%) with a further six (13%) reporting problems in the borderline
      range. Seven children (15%) were without significant problems in one or more area
      although only four of these (9%) were outside the borderline range for all of the
      sub-domains of the SDQ. DISCUSSION: A significant proportion of children with DCD
      were reported by their parents to be at risk of psychopathology. Further research
      is needed to understand the relationship between motor difficulties and emotional
      and behavioural symptoms; however, it is recommended that interventions for
      children with DCD should support mental health and behavioural problems as well
      as motor development.

PMID- 17018057
TI  - The common phospholipid-binding activity of the N-terminal domains of PEX1 and
      VCP/p97.
AB  - PEX1 is a type II AAA-ATPase that is indispensable for biogenesis and maintenance
      of the peroxisome, an organelle responsible for the primary metabolism of lipids,
      such as beta-oxidation and lipid biosynthesis. Recently, we demonstrated a
      striking structural similarity between its N-terminal domain and those of other
      membrane-related AAA-ATPases, such as valosine-containing protein (p97). The N
      terminal domain of valosine-containing protein serves as an interface to its
      adaptor proteins p47 and Ufd1, whereas the physiologic interaction partner of the
      N-terminal domain of PEX1 remains unknown. Here we found that N-terminal domains
      isolated from valosine-containing protein, as well as from PEX1, bind
      phosphoinositides. The N-terminal domain of PEX1 appears to preferentially bind
      phosphatidylinositol 3-monophosphate and phosphatidylinositol 4-monophosphate,
      whereas the N-terminal domain of valosine-containing protein displays broad and
      nonspecific lipid binding. Although N-ethylmaleimide-sensitive fusion protein,
      CDC48 and Ufd1 have structures similar to that of valosine-containing protein,
      they displayed lipid specificity similar to that of the N-terminal domain of PEX1
      in the assays. By mutational analysis, we demonstrate that a conserved arginine
      surrounded by hydrophobic residues is essential for lipid binding, despite very
      low sequence similarity between PEX1 and valosine-containing protein.

PMID- 17018058
TI  - Concerted mutation of Phe residues belonging to the beta-dystroglycan ectodomain
      strongly inhibits the interaction with alpha-dystroglycan in vitro.
AB  - The dystroglycan adhesion complex consists of two noncovalently interacting
      proteins: alpha-dystroglycan, a peripheral extracellular subunit that is
      extensively glycosylated, and the transmembrane beta-dystroglycan, whose
      cytosolic tail interacts with dystrophin, thus linking the F-actin cytoskeleton
      to the extracellular matrix. Dystroglycan is thought to play a crucial role in
      the stability of the plasmalemma, and forms strong contacts between the
      extracellular matrix and the cytoskeleton in a wide variety of tissues. Abnormal
      membrane targeting of dystroglycan subunits and/or their aberrant post
      translational modification are often associated with several pathologic
      conditions, ranging from neuromuscular disorders to carcinomas. A putative
      functional hotspot of dystroglycan is represented by its intersubunit surface,
      which is contributed by two amino acid stretches: approximately 30 amino acids of
      beta-dystroglycan (691-719), and approximately 15 amino acids of alpha
      dystroglycan (550-565). Exploiting alanine scanning, we have produced a panel of
      site-directed mutants of our two consolidated recombinant peptides beta
      dystroglycan (654-750), corresponding to the ectodomain of beta-dystroglycan, and
      alpha-dystroglycan (485-630), spanning the C-terminal domain of alpha
      dystroglycan. By solid-phase binding assays and surface plasmon resonance, we
      have determined the binding affinities of mutated peptides in comparison to those
      of wild-type alpha-dystroglycan and beta-dystroglycan, and shown the crucial role
      of two beta-dystroglycan phenylalanines, namely Phe692 and Phe718, for the alpha
      beta interaction. Substitution of the alpha-dystroglycan residues Trp551, Phe554
      and Asn555 by Ala does not affect the interaction between dystroglycan subunits
      in vitro. As a preliminary analysis of the possible effects of the aforementioned
      mutations in vivo, detection through immunofluorescence and western blot of the
      two dystroglycan subunits was pursued in dystroglycan-transfected 293-Ebna cells.

PMID- 17018059
TI  - Antioxidant Dps protein from the thermophilic cyanobacterium Thermosynechococcus
      elongatus.
AB  - DNA-binding proteins from starved cells (Dps proteins) protect bacteria primarily
      from oxidative damage. They are composed of 12 identical subunits assembled with
      23-symmetry to form a compact cage-like structure known to be stable at
      temperatures > 70 degrees C and over a wide pH range. Thermosynechococcus
      elongatus Dps thermostability is increased dramatically relative to mesophilic
      Dps proteins. Hydrophobic interactions at the dimeric and trimeric interfaces
      called Dps-like are replaced by salt bridges and hydrogen bonds, a common
      strategy in thermophiles. Moreover, the buried surface area at the least-extended
      Dps-like interface is significantly increased. A peculiarity of T. elongatus Dps
      is the presence of a chloride ion coordinated with threefold symmetry-related
      arginine residues lining the opening of the Dps-like pore toward the internal
      cavity. T. elongatus Dps conserves the unusual intersubunit ferroxidase centre
      that allows the Dps protein family to oxidize Fe(II) with hydrogen peroxide,
      thereby inhibiting free radical production via Fenton chemistry. This catalytic
      property is of special importance in T. elongatus (which lacks the catalase gene)
      in the protection of DNA and photosystems I and II from hydrogen peroxide
      mediated oxidative damage.

PMID- 17018060
TI  - Reframing birth: a consequence of cesarean section.
AB  - AIM: This paper is a report of a study to describe the childbirth expectations,
      influences and knowledge of a group of Western Australian women who experienced a
      cesarean section (CS) and would prefer a CS in a subsequent pregnancy.
      BACKGROUND: Evidence suggests that a previous CS is not an indication for an
      elective CS in a subsequent pregnancy, but western world data indicate high
      probability of repeat CS. METHODS: Community advertisements invited women who had
      experienced a CS to participate in a telephone interview. The thematic analysis
      presented in this paper is derived from data collected during 2003/2004 from 49
      participants who had initially expected to birth vaginal but had a CS and who had
      planned a CS in a subsequent pregnancy or stated that they would choose this
      option in a future pregnancy. FINDINGS: Before the first CS most women expected
      and wanted to give birth normally. After having a CS, however, many reframed
      vaginal birth as uncertain, unsafe and unachievable. For this group of women, the
      medical discourse that promoted CS as the safest option was a major influence on
      their decisions. As a result, they reconstructed CS as an acceptable alternative
      that was safer for them and their babies, allowed them to be better prepared, and
      was convenient. CONCLUSION: In the present climate, enabling women to keep birth
      'fear' in perspective may be an important strategy if we are to improve the
      uptake of vaginal birth after CS and the quality of care offered to women during
      the normal, but major, life event of childbirth.

PMID- 17018062
TI  - Partnering with patients--a concept ready for action.
AB  - AIM: This paper is a report of a concept analysis of partnership within the
      context of a professional-patient relationship. BACKGROUND: The concept of
      partnership has been previously characterized as immature, with a need for
      further consensus and consistency. Critical attributes previously reported
      include relationship, power sharing and negotiation, with empowerment as the
      primary consequence. METHOD: Rodgers' evolutionary method of analysis for concept
      development was used to re-examine the concept of partnership. Historical
      documents and previously published conceptual papers were reviewed for context. A
      search of multidisciplinary literature published between 2000 and 2004 was
      undertaken using the keywords of 'partnership' and 'partnering', combined with
      nurse/professional/physician-client relationship. Attributes, uses, antecedents
      and consequences were inductively derived from the citations analysed (n = 62).
      RESULTS: Previous authors affirmed that partnership involves a process and a
      consistent set of eight attributes. Relationship, shared power, shared decision
      making and patient autonomy are attributes that distinguish partnership from
      other related concepts. Most of the literature, however, consisted of expert
      opinion or descriptive research. Little progress has been made in applying
      theory, developing tools to test the process, identifying when partnerships are
      needed and what specific outcomes occur when they are present. CONCLUSION:
      Partnerships between healthcare providers and patients develop over time. They
      are created to support patients in having a greater voice in their care and to
      empower them in self-management. A descriptive model of partnership is proposed
      to support researchers in generating or applying existing theory to the
      development of research designs and tools that could test how this process
      actually works.

PMID- 17018063
TI  - Education needs for integrated care: a literature review.
AB  - AIM: This paper reports a systematic review to identify the education needs of
      the workforce within primary care to promote the effective delivery of integrated
      health and social care services. BACKGROUND: The need for different professionals
      to work more closely dominates global health policy. The drive to develop a
      workforce prepared for the future is crucial to the success of integrated
      services. However, some have argued that nurses are ill-equipped to meet the
      challenges of integrated service provision. The ability to work
      interprofessionally is an important skill which needs to be developed to support
      integrated working. METHODS: Structured searches were undertaken on
      organizational websites and the Caredata, CINAHL, Cochrane Library, MEDLINE,
      Sociofile databases between December 2002 and April 2004 to identify policy
      documents and primary research studies. The robustness of identified research
      studies were appraised using recognized appraisal tools. FINDINGS: Six themes
      were identified which indicate essential elements needed for integrated care. The
      need for effective communication between professional groups within teams and an
      emphasis on role awareness are central to the success of integrated services. In
      addition, education about the importance of partnership working and the need for
      professionals to develop skills in relation to practice development and
      leadership through professional and personal development is needed to support
      integrated working. CONCLUSION: Education which embeds essential attributes to
      integrated working is needed to advance nursing practice for interprofessional
      working. Further research exploring this and its impact on integrated provision
      is essential to ensure that evidence-based services are provided. The
      reinforcement of partnerships between higher education institutions and health
      and social care organizations should ensure that the workforce is educated to
      manage continuous change in service delivery. Innovative ways of teaching and
      learning which promote inter-professional working need to be explored.

PMID- 17018064
TI  - Legitimate family violence as represented in the print media: textual analysis.
AB  - AIM: This paper reports a study of how issues around the use of smacking by
      parents are represented in the print media. Our purpose was not to state a case
      for or against the use of smacking. Rather, within the contemporary social
      context we sought to answer the question, 'Why is smacking considered to be a
      legitimate part of parenting in the United Kingdom?' BACKGROUND: Although a
      number of government proposals aiming to ban the use of smacking by parents have
      been presented in the United Kingdom parliament and Scottish Executive, current
      legislation allows parents to use this form of physical discipline as long as it
      does not result in physical injury to the child. For the purposes of this
      discussion, smacking is considered as a social phenomenon rather than an activity
      simply to be favoured or to be opposed. METHOD: A sample of 244 articles from
      five different United Kingdom newspapers was examined during 2004. Schema
      analysis that drew upon semiotics was used to analyse these print media
      representations about the use of legitimate violence by parents towards children.
      FINDINGS: Newspaper reportage about the parental use of physical discipline has
      increased over the past 20 years. Only one newspaper (The Independent) published
      on this topic prior to 1994. The discourse about the use of physical discipline
      by parents has changed over time from one that focuses on the effectiveness of
      smacking to one that about the human rights of the child. The main themes
      identified in the print media discourse were the rights of the child, the
      effectiveness of smacking, long-term effects and consequences, and the role of
      the state. CONCLUSION: Media texts can influence and reinforce social dimensions
      of the label. The beliefs and attitudes of healthcare professionals and parents
      about smacking may be influenced by such representations.

PMID- 17018065
TI  - Physical environmental stimuli that turn healthcare facilities into healing
      environments through psychologically mediated effects: systematic review.
AB  - AIM: This paper reports a systematic review to determine the effects of physical
      environmental stimuli in healthcare settings on the health and well-being of
      patients. BACKGROUND: The concept of healing environments suggests that the
      physical environment of the healthcare setting can encourage the healing process
      and patients' feelings of well-being. Understanding the effects of physical
      environmental stimuli will allow us to design healthcare environments that
      generate these potential health benefits. METHOD: A search was conducted using
      the MedLine, PsychInfo, Embase, CINAHL, Iconda, ScienceDirect, Compendex and the
      ISI Citation Indexes databases. Studies were included if they concerned
      interventions involving health effects of environmental stimuli in healthcare
      settings on patients, and were based on controlled clinical trials published in
      peer-reviewed journals. Both clinical and psychological outcome measures were
      included. The search was completed in 2005. FINDINGS: Of the over 500 potentially
      relevant studies identified, only 30 met all criteria and were included in this
      review. Predominantly positive effects were found for sunlight, windows, odour
      and seating arrangements. Inconsistent effects were found for sound, nature,
      spatial layout, television and multiple stimuli interventions. In general, both
      the size and direction of effects seem highly dependent on characteristics of
      patient populations and healthcare settings. CONCLUSIONS: Studies that manipulate
      several environmental stimuli simultaneously clearly support the general notion
      that the physical healthcare environment affects the well-being of patients.
      However, when scrutinizing the effects of specific environmental stimuli,
      conclusive evidence is still very limited and difficult to generalize. The field
      thus appears to be in urgent need of well-conducted, controlled clinical trials.
      At present, and on the basis of the available research, it would be premature to
      formulate evidence-based guidelines for designing healthcare environments.

PMID- 17018066
TI  - Critical thinking dispositions in baccalaureate nursing students.
AB  - AIM: This paper reports an investigation into the critical thinking disposition
      of students enrolled in a baccalaureate nursing programme at a university in
      Korea. BACKGROUND: Critical thinking may be summarized as a skilled process that
      conceptualizes and applies information from observation, experience, reflection,
      inference and communication in a technical manner. It is more of a rational act
      used as an instrument rather than as a result. Critical thinking is a core
      competency in nursing and has been widely discussed in nursing education.
      However, the results of previous research on the effectiveness of nursing
      education in improving students' critical thinking have been inconsistent.
      METHODS: A longitudinal design was used with a convenience sample of 60 nursing
      students; 32 students participated four times in completing a questionnaire each
      March from 1999 to 2002. The California Critical Thinking Disposition Inventory
      was administered to measure disposition to critical thinking. RESULTS: There was
      a statistically significant improvement in critical thinking disposition score by
      academic year (F = 7.54, P = 0.0001). Among the subscales, open-mindedness, self
      confidence, and maturity also showed a statistically significant difference by
      academic year (P = 0.0194, 0.0041, 0.0044). CONCLUSION: Teaching strategies to
      enhance critical thinking should be developed, in addition to further research on
      the effect of the nursing curriculum on students' critical thinking. Moreover,
      survey instruments could be adjusted to incorporate characteristics of the Korean
      culture.

PMID- 17018067
TI  - Making sure the residents get their tablets: medication administration in care
      homes for older people.
AB  - AIM: This paper reports an exploratory study of issues concerning the nursing
      practice of altering medication dose forms prior to administration of medicines
      to residents in homes for older people. BACKGROUND: Medication use and
      administration is a major issue in residential homes for older people. Research
      suggests that the alteration of medication dose forms in these homes is a
      widespread practice. Despite its prevalence, there is limited nursing or
      pharmaceutical literature exploring the decision-making processes surrounding
      this practice, the methods by which medicines are altered, or the types of
      medicines which are modified. METHOD: Semi-structured interviews were carried out
      with 11 Registered Nurses working in a purposive sample of 10 residential homes
      for older people drawn from each of the six regions of South Australia. The data
      were collected in 2000. FINDINGS: Nurses felt constrained to ensure that
      prescribed medication was administered to residents, despite their concern that
      this was not without risk. Nurses were concerned that they were working in an
      information vacuum, due to limited information resources and informal
      communication with other healthcare professionals such as speech pathologists,
      pharmacists and general practitioners. There was also concern about the
      difficulty of coordinating information and policies about altering medications
      and of implementing appropriate procedures in individual facilities. CONCLUSION:
      Clinical guidelines for the processes surrounding the alteration of medication
      dose forms and relevant pharmaceutical information are needed in all residential
      homes for older people. Ongoing education for nurses in this area is also
      required.

PMID- 17018068
TI  - The 1999 Irish nurses' strike: nursing versions of the strike and self-identity
      in a general hospital.
AB  - AIM: The aim of this paper is to report findings from a study investigating
      nurses' experiences of strike in one public general hospital in the Republic of
      Ireland. BACKGROUND: October 1999 heralded the first nationwide nurses strike in
      the Republic of Ireland. The strike reflected an international shift towards
      industrial action in a profession which had previously viewed such action as the
      antithesis of professional behaviour. METHODS: A focused ethnographic approach
      studied a group of striking Registered Nurses, not as a culture per se, but as a
      collection of individuals sharing a common human experience. A purposive sampling
      approach identified eight information-rich cases from a modified quota structure.
      Semi-structured interviews were carried out immediately prior to, during and at
      the end of the 1999 strike. The participants also maintained journals which were
      explored during the interviews. Data were analysed using a constant comparative
      approach, seeking to achieve category saturation. FINDINGS: Four strike versions
      were identified. The anticipatory version is constructed as an inevitable
      protest, the orientation version as history-making solidarity and the performing
      version as a job of work. The withdrawal version is constructed as a conspiracy
      from which nurses are excluded. These versions portray ongoing tension that is
      experienced between conflicting self-identities of Registered Nurses as nurses
      and as strikers. The analysis revealed strategies adopted to resolve tensions
      between these identities within the dimensions of carer, patient advocate,
      multidisciplinary team member and professional. CONCLUSIONS: Debate on such
      potentially contentious issues by individual nurses, hospital managers and union
      leaders may facilitate awareness and preparation in advance of any future
      industrial action. Strategies that may be helpful in the event of a strike
      include a prestrike orientation programme for the entire organization, a support
      system for staff during the strike and informal de-briefing among all staff in
      the context of a social gathering when the strike is over.

PMID- 17018069
TI  - A comparative analysis of contemporary nurses' discontents.
AB  - AIM: This paper reports a study to evaluate and increase understanding of
      contemporary Registered Nurses' discontents, and to compare these discontents and
      their effects with those of nurses 20 years ago. BACKGROUND: In 1986, Turner
      argued that nurses' discontents were reflected in a discourse or 'vocabulary of
      complaint' that provided a sense of solidarity amongst practising nurses, and
      defused their frustrations rather than channelling them into demands for
      workplace reform. In this paper, we revisit Turner's notion of a vocabulary of
      complaint in the context of a study of nurse retention in the contemporary
      Australian healthcare workplace. METHODS: This paper draws on the qualitative
      data from a larger project (completed in 2001) exploring the relationship between
      job satisfaction and self-concept in both recently graduated and experienced
      nurses. Here, we elaborate on thematic analyses of the comments of 146 Australian
      Registered Nurses with more than 5 years' nursing experience. FINDINGS: There is
      still a high level of discontent amongst contemporary practising nurses, although
      the focus of their complaints and their responses to them have changed since
      Turner's study. Conflicting expectations of nurses and managers and lack of
      opportunity to provide comprehensive care emerged as the most important issues
      for experienced nurses today. Rather than contributing to a sense of solidarity
      as in Turner's study, contemporary nurses' discontents reflect intense personal
      frustration and underpin individual nurses' decisions to leave, or plan to leave,
      the workforce. CONCLUSION: There is an urgent need for increasing health service
      management and community awareness about the relationship between providing
      comprehensive nursing care and nurses' job satisfaction. Addressing nurses'
      discontents, wider nursing involvement in the international policy arena, and the
      politicization of nurses worldwide may contribute to alleviating the current
      global nursing shortage.

PMID- 17018070
TI  - Elemental analysis of human cremains using ICP-OES to classify legitimate and
      contaminated cremains.
AB  - The Tri-State Crematory Incident in Nobel, GA (February 2001) revealed
      limitations in traditional human cremated remains (cremains) analytical
      methodology. The goal of this study was to develop a method for effectively
      classifying questionable sets of cremains as legitimate or contaminated. Eighty
      eight samples of known human cremains, concrete, mixtures of the two, and
      questionable sets of cremains were acid digested and analyzed for 21 elements by
      Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES). Variable
      cluster and principle component analyses identified the seven elements (Sb, B,
      Li, Mn, Sr, Tl, and V) used to develop discriminant functions to classify
      questionable sets into two groups: cremains and concrete. The discriminant
      analysis shows that at the 0.90 probability level, mixtures of 50% or less human
      content were classified as concrete. Mixtures with 90% human content classified
      as cremains. Sixty percent and 75% human content mixtures remained in the
      questionable classification, but as the concentration of human increased in the
      mixture, the probability of assignment to the known cremains group increased.
      Most of the questionable human samples classified as cremains. This is a pilot
      study and cannot yet satisfy Daubert standards for courtroom admissibility, but
      it indicates that it is possible to determine the legitimacy of cremains using
      elemental analysis by ICP-OES coupled with multivariate statistical analysis.

PMID- 17018071
TI  - Frequencies of morphological characteristics in two contemporary forensic
      collections: implications for identification.
AB  - Positive identification relies on comparison of antemortem and postmortem data.
      Some identifications are based on morphological features such as fracture,
      pathological condition, and surgical hardware, despite little literature
      indicating the frequencies of such traits. This study examines whether such
      features are sufficiently rare as to be deemed individualizing. Data were
      collected on two modern North American skeletal collections (N=482 individuals).
      Presence/absence of features was scored by skeletal element and side. Results
      indicate that frequencies vary by geographic region (higher frequency of
      fractures and pathological conditions in New Mexico while individuals in
      Tennessee were more likely to have surgical interventions), many features such as
      fractures are remarkably common and that even suites of traits may not be
      individualizing. Caution is warranted when using written data rather than
      radiographic comparisons as the primary source of identification. The
      implications of these findings to missing person databases are also discussed.

PMID- 17018072
TI  - Morphometrics of the hyoid bone for human sex determination from digital
      photographs.
AB  - The identification of unknown remains is very important. When unknown remains are
      found, anthropologists first determine their sex and age. The sex of most
      skeletons is determined by their shape. In the hyoid bone, the shape is sex
      related, so it can be used forensically to determine the sex. This study focused
      on sex-based morphometry of the hyoid bone in Koreans using digital photographs.
      Hyoid bones from 52 males and 33 females were examined. For each subject, we took
      34 measurements from photographs using a computer program, and the data were
      analyzed statistically using SPSS 11.0. Twenty-one of 34 measurements had
      significant sex differences (p<0.05). The discriminant functions based on three
      measurements (X(1)-X(3)) were as follows: The accuracy of discriminant functions
      is 88.2% in both groups, so these can be used to distinguish males from females
      in a statistically significant manner.

PMID- 17018073
TI  - Metric assessment of the "mastoid triangle" for sex determination: a validation
      study.
AB  - Recently, a metric approach to skeletal sex determination was published by Paiva
      and Segre which is based on the summation of two triangular areas defined by
      three distinct craniometric landmarks: Porion, Mastoidale, and Asterion.
      According to the authors, values for the total triangle > or =1447.40 mm(2) are
      characteristic for male crania, while values < or =1260.36 mm(2) are indicative
      of female skulls (95% confidence). In order to evaluate the method's validity,
      two sex- and age-documented samples of different provenience were analyzed
      (N=197). The results show that while the indicated measurements display
      significant sex differences, the technique is of little practical meaning where a
      single individual must be independently classified. It is hypothesized that
      differences in the expression of sexual dimorphism as well as a population
      specific variability of the asterion location undermine the value of the mastoid
      triangle as a sex determinant.

PMID- 17018074
TI  - Metacarpal sexual determination in a Spanish population.
AB  - Anthropologists and forensic pathologist determine the sex of skeletons by
      analyzing quantitative and qualitative characters in the bone remains. Generally,
      the skull and os coxae are the elements most used, but they are not always
      preserved. In such cases, the investigator needs to have available other
      techniques based on different remains. The aim of the present work is to develop
      and describe discriminating functions for sex determination in a recent Spanish
      population using metacarpal morphology. A sample of bones corresponding to a
      contemporary Spanish population deposited at the Complutense University of Madrid
      (UCM) was analyzed. This sample comprised 697 metacarpals, corresponding to 79
      adult individuals (37 men and 42 women). These allowed us to obtain 120
      unifactorial discriminant functions. We selected the 10 equations, one for each
      metacarpal from both hands, that provided the best sexual discrimination. The
      correct sex classification rank progressed from 81%, for right (R) metacarpals IV
      and V, to 91%, for left (L) metacarpal II. The results suggest that metacarpals
      are structures that can be used for sex determination in paleoanthropological and
      forensic identifications.

PMID- 17018076
TI  - Anthropological and radiographic comparison of vertebrae for identification of
      decomposed human remains.
AB  - This case study demonstrates the importance of involving an anthropologist in
      forensic situations with decomposed remains. Anthropological consultation was
      used in conjunction with the comparison of antemortem and postmortem radiographs
      to establish positive identification of unknown, decomposed remains. The remains
      had no traditional identifying features such as fingerprints or dental. Through
      anthropological analysis, it was determined the decedent was male, between 20 and
      23 years at time of death and c. 5'2'' tall. This information allowed for a
      presumptive identification and a request for antemortem radiographs. The missing
      person was identified comparing the spinous processes of the cervical and
      thoracic vertebrae between ante- and postmortem radiographs.

PMID- 17018075
TI  - Blunt force cranial trauma in the Cambodian killing fields.
AB  - In this paper we present a unique pattern of blunt force cranial trauma that was
      observed in 10 of a sample of 85 crania from a Cambodian skeletal collection
      comprised of Khmer Rouge victims. Initial examination of the trauma, which
      presents as substantial damage to the occipital with fractures extending to the
      cranial base, suggested the pattern was classifiable as a basilar or ring
      fracture. However, further investigation, including trauma analysis and
      historical research, revealed that this fracture type is distinctive from basilar
      and ring fractures. Historical data indicate that a particular execution method
      was the likely source of the trauma. Recognition of this trauma pattern is
      significant because it exemplifies the distinct fracture configuration resulting
      from an apparently categorical and methodical execution technique. Identification
      of this fracture type could potentially assist forensic investigators in the
      recognition of specific methods of murder or execution.

PMID- 17018077
TI  - Simultaneous determination of total human and male DNA using a duplex real-time
      PCR assay.
AB  - A single duplex assay to determine both the amount of total human DNA and the
      amount of male DNA in a forensic sample has been developed. This assay is based
      on TaqMan technology and uses the multicopy Alu sequence to quantitate total
      human DNA and the multicopy DYZ5 sequence to quantitate Y chromosomal (male) DNA.
      The assay accepts a wide concentration range of input DNA (2 muL of 64 ng/microL
      to 0.5 pg/microL), and also allows detection of PCR failure. The PCR product
      sizes Alu (127 bp) and DYZ5 (137bp) approximate that of the smaller short tandem
      repeats (STRs) which should make the assay predictive of STR success with
      degraded DNA. The assay was optimized for probe/primer concentrations and BSA
      addition and validated on its reproducibility, on its human specificity, on its
      nonethnic variability, for artificial mixtures and adjudicated casework, for the
      effect of inhibitors and for state of DNA degradation. This assay should prove
      very usual in forensic analyses because knowing the relative amounts of male
      versus female DNA can allow the examiner to decide which samples may yield the
      most probative value in a case or direct the samples to methods that would yield
      the greatest information.

PMID- 17018078
TI  - A review of the analysis of vegetable oil residues from fire debris samples:
      analytical scheme, interpretation of the results, and future needs.
AB  - This paper reviews the literature on the analysis of vegetable (and animal) oil
      residues from fire debris samples. The examination sequence starts with the
      solvent extraction of the residues from the substrate. The extract is then
      prepared for instrumental analysis by derivatizing fatty acids (FAs) into fatty
      acid methyl esters. The analysis is then carried out by gas chromatography or gas
      chromatography-mass spectrometry. The interpretation of the results is a
      difficult operation seriously limited by a lack of research on the subject. The
      present data analysis scheme utilizes FA ratios to determine the presence of
      vegetable oils and their propensity to self-heat and possibly, to spontaneously
      ignite. Preliminary work has demonstrated that it is possible to detect chemical
      compounds specific to an oil that underwent spontaneous ignition. Guidelines to
      conduct future research in the analysis of vegetable oil residues from fire
      debris samples are also presented.

PMID- 17018079
TI  - Review of analytical techniques for arson residues.
AB  - Arson is a serious crime that affects society through cost, property damage, and
      loss of life. It is important that the methods and technologies applied by fire
      investigators in detection of evidence and subsequent analyses have a high degree
      of reliability, sensitivity, and be subject to rigorous quality control and
      assurance. There have been considerable advances in the field of arson
      investigation since the 1950s. Classification of ignitable liquids has been
      updated to include many new categories due to developments in the petroleum
      industry. Techniques such as steam or vacuum distillation and gas chromatography
      (GC) with flame ionization detection that may have been considered acceptable-
      even a benchmark--40 years ago, are nowadays generally disfavored, to the extent
      that their implementation may almost be considered as ignorance in the field. The
      advent of readily available mass spectrometric techniques has revolutionized the
      field of fire debris analysis, increasing the degree of sensitivity and
      discrimination possible considerably. Multi-dimensional GC--particularly GC x GC-
      while not yet widely applied, is rapidly gaining recognition as an important
      technique. This comprehensive review focuses on techniques and practices used in
      fire investigation, from scene investigation to analysis.

PMID- 17018080
TI  - Yield of illicit indoor cannabis cultivation in the Netherlands.
AB  - To obtain a reliable estimation on the yield of illicit indoor cannabis
      cultivation in The Netherlands, cannabis plants confiscated by the police were
      used to determine the yield of dried female flower buds. The developmental stage
      of flower buds of the seized plants was described on a scale from 1 to 10 where
      the value of 10 indicates a fully developed flower bud ready for harvesting.
      Using eight additional characteristics describing the grow room and cultivation
      parameters, regression analysis with subset selection was carried out to develop
      two models for the yield of indoor cannabis cultivation. The median Dutch illicit
      grow room consists of 259 cannabis plants, has a plant density of 15 plants/m(2),
      and 510 W of growth lamps per m(2). For the median Dutch grow room, the predicted
      yield of female flower buds at the harvestable developmental stage (stage 10) was
      33.7 g/plant or 505 g/m(2).

PMID- 17018081
TI  - Optimization of DNA extraction from low-yield and degraded samples using the
      BioRobot EZ1 and BioRobot M48.
AB  - Robotic extraction of DNA from dilutions of blood and semen using either the
      BioRobots EZ1 or BioRobots M48 consistently produced lower recoveries than
      standard organic extractions of the same samples. In an effort to increase the
      efficiency of robotically extracted DNA, glycogen and carrier RNA were added
      following cell lysis. The addition of glycogen, postlysis, resulted in no
      improvement in DNA recovery with the BioRobot EZ1. However, when carrier RNA was
      added to the cell lysate of limited and degraded samples extracted on the EZ1 or
      the M48, DNA recoveries dramatically increased four- to 20-fold. DNA yields
      obtained by robotic extraction in the presence of carrier RNA were as high, or
      higher, as those obtained by organic extraction lacking carrier RNA, while
      experiments that utilized carrier RNA in both types of extractions showed
      increased sensitivity for both methods. Furthermore, carrier RNA substantially
      increased the recovery of fragmented DNA with the EZ1.

PMID- 17018082
TI  - Assessing the potential of bacterial DNA profiling for forensic soil comparisons.
AB  - A pilot study was undertaken to evaluate DNA profiling of the bacterial community
      in soil as an alternative to geological methods for forensic soil comparisons.
      Soil samples from three different ecosystems were compared, and the variation
      within and between ecologically different sites was determined by using terminal
      restriction fragment (TRF) analysis of 16S ribosomal DNA. Comparison of TRF
      profiles revealed that samples from within a specific ecosystem (e.g., a field)
      showed a significantly higher similarity to each other than to those from another
      ecosystem (e.g., a forest). In addition, some profile features were unique to
      specific ecosystems. These features may allow the determination of characteristic
      profiles that will facilitate identification of ecologically different sites, so
      that a given sample collected from a suspect could be identified as originating
      from, for example, a field, rather than a forest. The implications of these
      preliminary findings for forensic investigations are discussed.

PMID- 17018083
TI  - Characterization of the N+3 stutter product in the trinucleotide repeat locus
      DYS392.
AB  - Stutter products generated during DNA amplification by the polymerase chain
      reaction (PCR) may complicate mixture interpretation. The PCR amplification of
      the DYS392 locus typically results in three distinct detectable PCR products: the
      true allele product (N), a stutter product three bases smaller (N-3), and a
      reproducible low-level product, three bases larger (N+3). Sequence analysis of
      the N+3 product demonstrated that its sequence is one TAT repeat longer than the
      true allele product. Our experiments demonstrated that the quantity of both N-3
      and N+3 stutter increased as the allele number increased. The percent stutter
      also increased as the magnesium concentration was increased in the reaction, as
      well as when the amount of input DNA was decreased. As both stutter products
      behave in a similar and reproducible fashion, the same rules that apply to the
      interpretation of N-3 stutter products in short tandem repeat analysis, can be
      applied to N+3 stutters. The characterization of the DYS392 N+3 product is the
      first detailed published study of a stutter product larger than the true allele.

PMID- 17018084
TI  - The successful DNA typing of samples following a thermal cycler power loss.
AB  - An approach for generating DNA profiles when critical samples have been consumed
      and a power outage occurs during the polymerase chain reaction (PCR)
      amplification reaction is described. This study demonstrates that a complete and
      accurate DNA short tandem repeat profile can be obtained: (1) when single source
      DNA samples are amplified for 26, 27, or 28 cycles using the Profiler Plus and
      COfiler Amplification Kits after an interruption in amplification, (2) from mock
      samples when PCR amplification has been interrupted early (after five cycles) or
      late (after 18 cycles) and the sample is subjected to an additional round of
      amplification, even after incubation of the sample at room temperature overnight,
      and (3) from nonprobative casework samples interrupted after approximately 18
      cycles of amplification, an overnight incubation at room temperature and
      subjected to one or two additional rounds of PCR amplification for approximately
      26 total cycles. Samples interrupted before five completed cycles and subjected
      to additional PCR cycles yielded variable results.

PMID- 17018085
TI  - A rapid test for heroin (3,6-diacetylmorphine) based on two chemiluminescence
      reactions.
AB  - A rapid method for screening drug seizure samples for 3,6-diacetylmorphine
      (heroin), which consists of a simple hydrolysis procedure and flow-injection
      analysis with two chemiluminescence reagents, is described. Before hydrolysis,
      3,6-diacetylmorphine evokes an intense response with a tris(2,2'
      bipyridyl)ruthenium(III) reagent (prepared by dissolving the perchlorate salt in
      acetonitrile), and a relatively weak chemiluminescence response with a second
      reagent: potassium permanganate in an aqueous acidic polyphosphate solution.
      However, the permanganate reagent is extremely sensitive toward the hydrolysis
      products of 3,6-diacetylmorphine (i.e., 6-monoacetylmorphine and morphine). Some
      compounds commonly found in drug laboratories may cause false positives with
      tris(2,2'-bipyridyl)ruthenium(III), but do not produce the markedly increased
      response with the permanganate reagent after the hydrolysis procedure. The
      combination of these two tests therefore provides an effective presumptive test
      for the presence of 3,6-diacetylmorphine, which we have verified with 14 samples
      obtained from a forensic science laboratory.

PMID- 17018086
TI  - A versatile technique for the investigation of gunshot residue patterns on
      fabrics and other surfaces: m-XRF.
AB  - With heavy-metal-free ammunitions becoming more and more popular, it is necessary
      to find methods to visualize patterns of those elements in gunshot residues
      (GSRs) that are not accessible by chemographic coloring tests. The recently
      introduced millimeter-X-ray fluorescence analysis (m-XRF) spectrometer Spectro
      Midex M offers an easy way to record mappings of GSRs containing such elements in
      order to determine shooting distances as well as the general composition of these
      particles. A motorized stage enables samples of a maximum size of 20 x 20 cm to
      be investigated, like fabric, clothes, adhesive tapes (Filmolux films), and
      polyvinylalcohol gloves of shooter's hands. Human tissues can be measured using a
      Peltier-cooled specimen holder that is mounted onto the stage. As the spot size
      of the exiting X-rays lies in the millimeter range, which is adequate for the
      assessment of the residue patterns for shooting distance determination, a
      significant reduction in measurement time is achieved compared with mu-XRF
      methods. Test shots with heavy-metal-free ammunitions were performed on different
      target materials, like pork skin and fabric, and the elemental distributions of
      Ti, K, and Ga were determined. In order to show the capability of the
      spectrometer for conventional lead ammunitions as well, a shot series of 5-100 cm
      shooting distance and an adhesive tape of a shooter's hand were investigated
      analogously. A comparison of several methods applied in GSR investigation shows
      the advantages of the m-XRF method.

PMID- 17018087
TI  - Visualization of gunshot residue patterns on dark clothing.
AB  - Determination of the muzzle-to-target distance is often a critical factor in
      criminal and civil investigations involving firearms. However, seeing and
      recording gunshot residue patterns can be difficult if the victim's clothing is
      dark and/or bloodstained. Trostle reported the use of infrared film for the
      detection of burn patterns. However, only after the film is developed are the
      results visible and multiple exposures at different settings may be needed. The
      Video Spectral Comparator 2000 (Foster & Freeman Ltd., Evesham, Worcestershire,
      U.K.) is an imaging instrument routinely used by forensic document examiners.
      Without use of specialized film could the VSC 2000 (at appropriate instrument
      settings) quickly, easily, and reliably provide instantaneous viewing, saving,
      and printing of gunshot residue patterns on dark and/or blood soaked clothing? At
      muzzle-to-target distances of 6, 12, and 18 in., test fires were made into five
      different types of dark clothing using eight different handguns of different
      calibers. Gunshot residues were detected for all eight calibers, and powder burn
      patterns were seen on dark clothing for all three target distances and calibers
      except 0.22 long rifle and 0.25 ACP. Bloodstains did not preclude the viewing of
      these patterns.

PMID- 17018088
TI  - GC-MS analysis of hashish samples: a case of adulteration with colophony.
AB  - This report describes the analytical characterization of 16 hashish samples
      confiscated in Italy. The samples were solvent extracted and subjected to GC-MS
      analysis for the separation and quantitation of the main cannabinoids. One of the
      analyzed samples was shown to contain extraneous compounds, identified as resin
      acids characteristic of colophony (rosin). Colophony is a natural resinous
      product obtained from various species of pine, spruce, and larch; it is a skin
      sensitizer and its fumes produce nonspecific irritation that can cause bronchial
      asthma. Similar adulterations of hashish have not been reported previously;
      therefore, at present there is no information about the effects of smoking
      colophony or a combination of hashish and colophony. It is presumed, however,
      that such a combination would be highly detrimental to the health of the user.

PMID- 17018089
TI  - Extent, trends, and perpetrators of prostitution-related homicide in the United
      States.
AB  - Prostitute women have the highest homicide victimization rate of any set of women
      ever studied. We analyzed nine diverse homicide data sets to examine the extent,
      trends, and perpetrators of prostitution-related homicide in the United States.
      Most data sources substantially under-ascertained prostitute homicides. As
      estimated from a conservative capture-recapture analysis, 2.7% of female homicide
      victims in the United States between 1982 and 2000 were prostitutes. Frequencies
      of recorded prostitute and client homicides increased substantially in the late
      1980s and early 1990s; nearly all of the few observed pimp homicides occurred
      before the late 1980s. These trends may be linked to the rise of crack cocaine
      use. Prostitutes were killed primarily by clients, clients were killed mainly by
      prostitutes, and pimps were killed predominantly by pimps. Another conservative
      estimate suggests that serial killers accounted for 35% of prostitute homicides.
      Proactive surveillance of, and evidence collection from, clients and prostitutes
      might enhance the investigation of prostitution-related homicide.

PMID- 17018090
TI  - The use of bloodhounds in determining the impact of genetics and the environment
      on the expression of human odortype.
AB  - Bloodhounds are used to trail fleeing felons and missing persons. In order to
      start a trail, the dog must be presented with a person's scent. There are many
      hypotheses on what a bloodhound smells while trailing. The present study attempts
      to identify whether human scent is genetic, and if it is influenced by one's
      environment. Bloodhounds trained in human scent discrimination were used to
      differentiate between monozygotic twins, related and nonrelated persons, living
      together and apart. The first test required the dogs to run blind trails after
      being presented with the scent of one person in the pair, while the opposite
      person was hidden. The second test allowed the dogs to trail one person in the
      pair after both people were hidden. Results appear to demonstrate that
      bloodhounds rely heavily on genetic cues when differentiating between people.
      Environmental cues do not appear to significantly aid the bloodhound in scent
      discrimination.

PMID- 17018091
TI  - A motion detection-based framework for improving image quality of CCTV security
      systems.
AB  - Closed-circuit television (CCTV) security systems have been widely used in banks,
      convenience stores, and other facilities. They are useful to deter crime and
      depict criminal activity. However, CCTV cameras that provide an overview of a
      monitored region can be useful for criminal investigation but sometimes can also
      be used for object identification (e.g., vehicle numbers, persons, etc.). In this
      paper, we propose a framework for improving the image quality of CCTV security
      systems. This framework is based upon motion detection technology. There are two
      cameras in the framework: one camera (camera A) is fixed focus with a zoom lens
      for moving-object detection, and the other one (camera B) is variable focus with
      an auto-zoom lens to capture higher resolution images of the objects of interest.
      When camera A detects a moving object in the monitored area, camera B, driven by
      an auto-zoom focus control algorithm, will take a higher resolution image of the
      object of interest. Experimental results show that the proposed framework can
      improve the likelihood that images obtained from stationary unattended CCTV
      cameras are sufficient to enable law enforcement officials to identify suspects
      and other objects of interest.

PMID- 17018092
TI  - Contemporary methods of labeling dental prostheses--a review of the literature.
AB  - Forensic identification (ID) based on an assessment of the dentition is
      commonplace. However, despite an increase in the oral health of Western
      populations, there are still many millions of individuals who are edentulous and
      whom have been treated with completed dentures. In the United Kingdom alone over
      300,000 patients are rendered edentulous each year. In order to facilitate the ID
      of such individuals a number of forensic and governmental organizations have
      recommended that dentures be labeled. A number of labeling systems exist which
      can be broadly separated into inclusion systems, marking systems, and novel
      methods. Each of the commonly described systems are demonstrated with an
      assessment of their strengths and weaknesses. It is recommended that an inclusion
      denture marker, preferably metallic, should be used in order to withstand the
      most common postmortem assaults.

PMID- 17018093
TI  - Use of "therapeutic complication" as a manner of death.
AB  - Analyses of deaths due to therapeutic complications (TCs) provide important
      quality of care information for medical providers. In New York City, 463 deaths
      were investigated by the Office of Chief Medical Examiner and certified with TC
      as the manner of death in 2003. The TC manner of death is used for fatalities due
      to predictable complications of appropriate medical therapy. All death
      certificates and select autopsy, hospital, and investigation reports were
      reviewed. Data concerning cause of death, contributing conditions, age, race, and
      sex were extracted. The types of complications and the causes of death were
      classified into various types of surgical and nonsurgical categories of
      complications. These included: postoperative infections, pulmonary emboli, and
      technical and medication complications. The use of TC as a manner of death has
      benefits and limitations. Without the TC option, one is forced to certify certain
      deaths (e.g., penicillin anaphylaxis) either as natural or accident. The TC
      option allows easy identification and tracking of medical complications for
      public health purposes and also allows more consistent reporting of natural and
      medical-accidental deaths. In general, complications that occur during emergency
      surgeries/procedures for natural disease, tend to be certified with a natural
      manner. The "but for" test may be used to distinguish natural from TC deaths.
      There are criteria for distinguishing TC from accidents and homicides. TCs that
      occur during treatment of a potentially life-threatening injury, are superseded
      by the manner dictated by the circumstances of the initiating injury. The
      certification of TC usually does not address errors of omission, clinical
      judgement/management, or missed diagnoses.

PMID- 17018094
TI  - Reduction of postmortem angiography-induced tissue edema by using polyethylene
      glycol as a contrast agent dissolver.
AB  - Postmortem investigation is increasingly supported by computed tomography (CT)
      and magnetic resonance imaging, in which postmortem minimal invasive angiography
      has become important. The newly introduced approach using an aqueous contrast
      agent solution provided excellent vessel visualization but was suspected to
      possibly cause tissue edema artifacts in histological investigations. The aim of
      this study was to investigate on a porcine heart model whether it is possible to
      influence the contrast agent distribution within the soft tissue by changing its
      viscosity by dissolving the contrast agent in polyethylene glycol (PEG) as a
      matrix medium. High-resolution CT scans after injection showed that viscosities
      above c. 15 mPa s (65% PEG) prevented a contrast agent distribution within the
      capillary bed of the left ventricular myocardium. Thereby, the precondition of
      edema artifacts could be reduced. Its minimal invasive application on human
      corpses needs to be further adapted as the flow resistance is expected to differ
      between different tissues.

PMID- 17018095
TI  - Immunohistochemical staining as a potential method for the identification of
      vaginal epithelial cells in forensic casework.
AB  - There is currently no accurate method to identify vaginal epithelial cells
      uniquely. This study aimed to use a cell extraction procedure compatible with
      routine forensic sampling methods, and to investigate the expression of
      cytokeratin (CK), estrogen receptor-alpha (ERalpha), and phosphodiesterase 5
      (PDE5) in order to distinguish between skin, buccal, vaginal, and external penile
      epithelial cells. Seminal fluid samples were also examined. Epithelial cell
      samples were fixed in formalin, embedded in agarose, and processed using
      histological methods. Antigen-antibody reactions were detected using the DAKO
      Envision+ detection system. CK was present in all cells from all five sources
      confirming the origin of cells as epithelial. Both ERalpha and PDE5 positively
      labeled vaginal, buccal, and skin epithelial cells. Although an antigen unique to
      vaginal epithelial cells was not identified, we have described a cell extraction
      procedure for use in the immunohistochemical detection of a wide range of
      antigens, an approach compatible with forensic diagnostics.

PMID- 17018096
TI  - Sudden death from saccular laryngeal cyst.
AB  - Laryngeal cysts are benign, uncommon lesions of the larynx that have been
      reported on rare occasions to cause sudden death in infants and adults by acute
      airways obstruction. In this report, we document the sudden death of a 36-year
      old woman from a previously undiagnosed, asymptomatic laryngeal saccular cyst
      that presented with acute, and consequent fatal, airway obstruction. Difficulty
      during intubation, both in theater and in emergency settings, is a frequent
      presenting problem. This can have significant medicolegal implications in
      determining possible negligence. The diagnosis, classification, and management of
      such cysts, and their importance to both the forensic pathologist and clinicians
      are discussed.

PMID- 17018097
TI  - Sudden death in infancy due to bicuspid aortic valve.
AB  - Symptoms of bicuspid aortic valve usually occur in the age group of 50-70 years,
      but rarely, it can also lead to sudden unexpected death in infancy and early
      childhood. The autopsy of a 2-month-old baby boy, found dead in his cot, revealed
      the heart weight as 25 g, and the macroscopic examination showed the
      circumference of the aortic valve consisting of two leaflets as 8 mm. The
      thickness of the left ventricle, right ventricle, and septum was measured as 8,
      7, and 10 mm, respectively. Microscopically, the heart revealed hypertrophic
      changes of myocytes. Subendocardial areas displayed necrosis of myocytes, and
      severe and diffuse ischemic changes characterized by loss of myofibers and
      vacuolization. Interstitial pneumonia was identified in the lungs. Death occurred
      as a result of a congenital bicuspid aortic valve obstructing the left
      ventricular outflow tract complicated by lung infection. As there are only a few
      reported cases in infancy, and congenital bicuspid aortic valve can lead to
      sudden unexpected death, this case is presented to the forensic community.

PMID- 17018098
TI  - A forensic entomology case from the Amazon rain forest of Brazil.
AB  - The first case of application of forensic entomology in the Brazilian Amazonia is
      described. The corpses of 26 men were found in the rainforest in Rondonia State,
      Brazil. Fly larvae collected on the bodies during autopsy were identified as
      Paralucilia fulvinota (Diptera, Calliphoridae). No data or specimens were
      collected at the crime scene. At the laboratory, the larvae developed into pupae
      in 58 h and into adults in 110.5 h. The total development time for P. fulvinota
      was measured in field experiments inside the forest. The age of the larvae when
      collected from the bodies was estimated as the difference between the time
      required for them to become adults and the total development time for this
      species. The estimated age of the maggots and the minimum postmortem interval was
      5.7 days.

PMID- 17018099
TI  - Fatal bromethalin poisoning.
AB  - Bromethalin is a neurotoxin found in some rodenticides. A delusional 21-year-old
      male presented to a hospital with altered mental status the day after ingesting a
      bromethalin-based rodenticide. He died 7 days after his self-reported exposure to
      c. 17 mg bromethalin (equivalent to 0.33 mg bromethalin/kg). His
      clinicopathologic course was characterized by altered mental status, obtundation,
      increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse
      histologic vacuolization of the white matter in the central nervous system seen
      on microscopic examination at autopsy. The presence of a demethylated form of
      bromethalin in the patient's liver and brain was confirmed by gas chromatography
      with mass spectrometry. Clinical signs and lesions observed in this patient are
      similar to those seen in animals poisoned with bromethalin. This case illustrates
      the potential for bromethalin ingestion to result in fatal human poisoning.

PMID- 17018100
TI  - Suicidal asphyxiation by inhalation of automobile emission without carbon
      monoxide poisoning.
AB  - Reported herein is the suicidal asphyxiation of a young man due to exhaustion of
      oxygen in the interior of a sealed automobile into which the exhaust emissions
      were diverted. His blood carboxyhemaglobin concentration was less than 5%
      saturation. The car was equipped with a catalytic converter and when tested, the
      exhaust carbon monoxide concentration was 0.01%.

PMID- 17018101
TI  - Adult Hirschsprung's disease diagnosed during forensic autopsy.
AB  - We report a case of fatal Hirschsprung's disease (HD) discovered at autopsy. A 20
      year-old man collapsed at home. Emergency medical personnel found him in cardiac
      arrest and all resuscitative efforts failed. He had a past history of chronic
      constipation since infancy. Forensic autopsy revealed a megacolon full of gas and
      stools. Microscopic examination showed absence of ganglion cells in a short
      segment of the rectum and enterocolitis in the left and transverse colon. HD is
      rarely described in adults. In many cases, patients complained of constipation
      since infancy but the affection remained misdiagnosed. The relative good
      tolerance of the disease is usually due to a short aganglionic bowel segment.
      Enterocolitis is a frequent and severe complication of HD in children but is
      rarely described in adults. This case suggests the importance of HD diagnosis in
      childhood in order to avoid fatal complications with forensic consequences.

PMID- 17018102
TI  - Three species of insects collected from an adult human corpse above 3300 m in
      elevation: a review of a case from Colorado.
AB  - We report on the colonization of an adult human corpse by three insect species at
      3350 m (11,000 ft) in elevation. The adult silphid Thanatophilus coloradensis
      (Wickham), adults of the blow fly Calliphora coloradensis (Hough), and larvae and
      adults of Lucilia silvarum (Meigen) were all collected from the victim's body
      which had been wrapped in plastic. The victim was found in late June in the Rocky
      Mountains of Colorado. This paper provides additional confirmation of the taxa
      utilizing a human corpse at high elevations in Colorado.

PMID- 17018103
TI  - Fatal accidental intrathecal injection of vindesine.
AB  - A 25-year-old woman being treated for non-Hodgkin's lymphoma was accidentally
      given vindesine intrathecally. The error was recognized immediately and a spinal
      cord washing was performed through syringing with isotonic saline. However, the
      patient died 6 weeks later with increasing paralysis, which was followed by
      neurologic failure. The deceased was autopsied and the central nervous system was
      removed for a microscopic examination. The results showed microscopic lesions
      extending from the lumbar to the thoracic portion of the spinal cord, which
      included pseudocystic transformation of the cells, degeneration of myelin, and
      microhemorrhages. The brain was edematous and, in the cerebellum, the vermis
      showed a loss of granule and Purkinje cells. The authors compare this report on
      vindesine toxicity with cases in the literature involving vincristine. The
      treating physician admitted responsibility and was sentenced to both a fine and
      imprisonment.

PMID- 17018104
TI  - Suicides in the young people of Geneva, Switzerland, from 1993 to 2002.
AB  - Suicides in Geneva in those less than 25 years old, from 1993 to 2002, were
      reviewed. Scenes investigations, autopsy findings, toxicology results, and
      psychiatric history (when available) were examined. There were 65 cases. The
      average annual suicide rate was 11/100,000. Seventy-seven percent were male, and
      23% were female. The youngest was 12 years old and most of the victims were 18
      years old and over (89%). For men, the use of firearms was the most common method
      (38%), followed by fall from height (16%) and drowning (10%). For women, fall
      from height was the most frequent (40%), followed by firearms and medication
      overdoses (20% each), hanging (13%), and drowning (7%). Toxicological analysis
      was performed in 41% of the cases and showed that alcohol was present in 26% and
      other drugs in 67% of these cases. The most common drugs present were
      benzodiazepines, cannabis, and cocaine.

PMID- 17018105
TI  - Criminal-thinking styles and illegal behavior among college students: validation
      of the PICTS.
AB  - The present study examined the relation of self-reported criminal-thinking styles
      and self-reported illegal behavior among college students. Participants were 177
      male and 216 female (N=393) undergraduate students. Participants were divided by
      gender and further classified into four groups of self-reported illegal behavior:
      control-status offenses, drug crimes, property crimes, and violent crimes against
      people. The psychological inventory of criminal-thinking styles (PICTS) (1)
      measured criminal-thinking patterns on eight scales. Results indicated that males
      who committed violent crimes against people endorsed significantly higher levels
      of distorted criminal-thinking patterns on all scales than the control-status
      offenses, and drug crimes groups. Interestingly, female participants who
      committed property crimes displayed six significantly elevated PICTS scales
      whereas females with violent crimes against people had significant elevations on
      only four of the criminal-thinking style scales. These results extend Walter's
      initial validation of the PICTS with incarcerated respondents to a non
      incarcerated population and show potential use of the PICTS with other
      populations.

PMID- 17018106
TI  - Sleep apnea as a possible factor contributing to aggression in sex offenders.
AB  - Sleep disorders, such as obstructive sleep apnea (OSA), are often unrecognized
      and undertreated. A disruption in normal sleep may be associated with increased
      irritability and aggression. To elucidate further the impact of OSA on hostility
      of forensic patients, we performed a retrospective chart review of 10 consecutive
      outpatient sex offenders who were diagnosed with OSA and treated with continuous
      positive airway pressure (CPAP). The Buss-Perry Aggression Questionnaire was
      compared pre- and posttreatment. Following treatment, the total Buss-Perry score
      was significantly lower, with lower scores on the anger, physical aggression,
      hostility, and verbal aggression subscales. These results suggest that in sex
      offenders suffering from OSA, aggression and hostility may be significantly
      reduced through CPAP treatment. Further investigation is required to investigate
      if reducing aggression and hostility in this manner impacts recidivism and
      overall functioning.

PMID- 17018107
TI  - Concentration of carbon monoxide (CO) in postmortem human tissues: effect of
      environmental CO exposure.
AB  - We studied how carbon monoxide (CO) is distributed within the human body through
      quantitation of CO concentrations in postmortem tissue samples from fatalities
      including possible CO exposure. Stored, frozen tissues were diced, sonicated in
      water, and 0.01-8.0 mg wet weight (ww) tissues were incubated with sulfosalicylic
      acid in CO-purged, septum-sealed vials. CO released into the headspace was
      quantitated by reduction gas chromatography. Mean tissue CO concentrations
      (pmol/mg ww) from subjects diagnosed to have no known CO exposure (control,
      N=14), died from fire (N=13), and CO asphyxiation (N=7), respectively, were:
      adipose (2;13;9), brain (3;13;65), muscle (15;97;297), heart (30;99;371), kidney
      (22;432;709, lung (54;690;2638), spleen (73;1366;3548), and blood
      (162;2238;5070). Carboxyhemoglobin concentrations were 1.4%, 25.2%, and 69.1% of
      total hemoglobin, respectively. We conclude that measurements of CO concentration
      in a variety of tissues can be used as markers for the degree of exogenous CO
      exposure and the identification of possible causes of death.

PMID- 17018108
TI  - Changing patterns of drug and alcohol use in fatally injured drivers in
      Washington State.
AB  - We have previously reported on patterns of drug and alcohol use in fatally
      injured drivers in Washington State. Here we revisit that population to examine
      how drug use patterns have changed in the intervening 9 years. Blood and serum
      specimens from drivers who died within 4 h of a traffic accident between February
      1, 2001, and January 31, 2002, were analyzed for illicit and therapeutic drugs
      and alcohol. Drugs when present were quantitated. Samples suitable for testing
      were obtained from 370 fatally injured drivers. Alcohol was detected above 0.01
      g/100 mL in 41% of cases. The mean alcohol concentration for those cases was 0.17
      g/100 mL (range 0.02-0.39 g/100 mL). Central nervous system (CNS) active drugs
      were detected in 144 (39%) cases. CNS depressants including carisoprodol,
      diazepam, hydrocodone, diphenhydramine, amitriptyline, and others were detected
      in 52 cases (14.1%), cannabinoids were detected in 47 cases (12.7%), CNS
      stimulants (cocaine and amphetamines) were detected in 36 cases (9.7%), and
      narcotic analgesics (excluding morphine which is often administered
      iatrogenically in trauma cases) were detected in 12 cases (3.2%). For those cases
      which tested positive for alcohol c. 40% had other drugs present which have the
      potential to cause or contribute to the driver's impairment. Our report also
      considers the blood drug concentrations in the context of their interpretability
      with respect to driving impairment. The data reveal that over the past decade,
      while alcohol use has declined, some drug use, notably methamphetamine, has
      increased significantly (from 1.89% to 4.86% of fatally injured drivers) between
      1992 and 2002. Combined drug and alcohol use is a very significant pattern in
      this population and is probably overlooked in DUI enforcement programs.

PMID- 17018109
TI  - Genetic profile of three short tandem repeat loci CSF1PO, TPOX, and TH01 in a
      Chinese Korean population.

PMID- 17018110
TI  - Distribution of D4S1654, D4S3255, and GATA148G10 alleles in a Chinese population
      sample.

PMID- 17018111
TI  - Genetic variation for five short tandem repeat loci in a Central China population
      sample.

PMID- 17018112
TI  - Allele frequency of D13S1491 and D16S768 in two populations.

PMID- 17018113
TI  - Allele frequencies of D2S2960 and GATA149B10 in two populations.

PMID- 17018114
TI  - Allele frequency data for nine STRs polymorphism in a Gurkha population of
      Malaysia.

PMID- 17018115
TI  - Y chromosome STR haplotypes and allele frequencies in Illinois Caucasian, African
      American, and Hispanic males.

PMID- 17018116
TI  - Guatemala mestizo population data on 15 STR loci (Identifiler Kit).

PMID- 17018117
TI  - Population data at two short tandem repeat loci D2S1338 and D19S433 in the sample
      of multinational Bosnia and Herzegovina residents.
AB  - POPULATION: We have analyzed the distribution of allele frequencies at two short
      tandem repeats loci (D2S1338 and D19S433) in a multinational sample of Bosnia and
      Herzegovina (B&H) residents. A total of 110 unrelated male and female individuals
      (Caucasians) from different regions of B&H were sampled for the analysis. We
      ensured that the sample reflected approximate proportional participation of the
      three main ethnic groups in the population of B&H (Bosniacs-Muslim [45%], Serbs
      [34%], Croats [21%]).

PMID- 17018119
TI  - The Na(+)/H(+) exchanger is a major pH regulator in GABAergic presynaptic nerve
      terminals synapsing onto rat CA3 pyramidal neurons.
AB  - The effects of pH(i) on GABAergic miniature inhibitory postsynaptic currents
      (mIPSCs) were studied in mechanically dissociated CA3 pyramidal neurons, by use
      of ammonium prepulse and whole-cell patch-clamp techniques, under the voltage
      clamp condition. NH(4)Cl itself, which is expected to alkalinize pH(i), increased
      GABAergic mIPSC frequency in a concentration-dependent manner. In contrast,
      NH(4)Cl decreased mIPSC frequency, either in the presence of 200 microm Cd(2+) or
      in Ca(2+)-free external solution, suggesting that intraterminal alkalosis
      decreased GABAergic mIPSC frequency while [NH4(+)] itself may activate Ca(2+)
      channels by depolarizing the terminal. On the other hand, GABAergic mIPSC
      frequency was greatly increased immediately after NH(4)Cl removal, a condition
      expected to acidify pH(i), and recovered to the control level within 2 min after
      NH(4)Cl removal. This explosive increase in mIPSC frequency observed after
      NH(4)Cl removal was completely eliminated after depletion of Ca(2+) stores with 1
      microm thapsigargin in the Ca(2+)-free external solution, suggesting that
      acidification increases in intraterminal Ca(2+) concentration via both
      extracellular Ca(2+) influx and Ca(2+) release from the stores. However, the
      acidification-induced increase in mIPSC frequency had not recovered by 10 min
      after NH(4)Cl removal either in the Na(+)-free external solution or in the
      presence of 10 microm 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), a specific
      Na(+)/H(+) exchanger (NHE) blocker. The present results suggest that NHEs are
      major intraterminal pH regulators on GABAergic presynaptic nerve terminals, and
      that the NHE-mediated regulation of pH(i) under normal physiological or
      pathological conditions might play an important role in the neuronal excitability
      by increasing inhibitory tones.

PMID- 17018120
TI  - Informed consent for facial transplantation.
AB  - Now that partial face transplantation has been performed, attention is focused on
      likely functional, aesthetic and immunological outcomes, and full facial
      transplantation is the likely next step. Facial transplantation has been the
      source of ethical debate, a key part of which focuses on valid informed consent.
      We review the process of informed consent in health settings, assessing how
      applicable the current standards are for facial transplantation. The factors
      which need to be assessed during the screening programme are outlined. We
      conclude that both individual and process factors are important in obtaining
      consent for radical new procedures, and outline our own gold standard for
      ensuring informed consent in facial transplantation.

PMID- 17018121
TI  - Composite tissue allotransplantation of the hand and face: a new frontier in
      transplant and reconstructive surgery.
AB  - Each year an estimated 7-million people in the USA need composite tissue
      reconstruction because of surgical excision of tumors, accidents and congenital
      malformations. Limb amputees alone comprise over 1.2 million of these. This
      figure is more than double the number of solid organs needed for transplantation.
      Composite tissue allotransplantation in the form of hand and facial tissue
      transplantation are now a clinical reality. The discovery, in the late 1990s,
      that the same immunotherapy used routinely in kidney transplantation was also
      effective in preventing skin rejection made this possible. While these new
      treatments seem like major advancements most of the surgical, immunological and
      ethical methods used are not new at all and have been around and routinely used
      in clinical practice for some time. In this review of composite tissue
      allotransplantation, we: (i) outline the limitations of conventional
      reconstructive methods for treating severe facial disfigurement, (ii) review the
      history of composite tissue allotransplantation, (iii) discuss the chronological
      scientific advances that have made it possible, (iv) focus on the two unique
      clinical scenarios of hand and face transplantation, and (v) reflect on the
      critical issues that must be addressed as we move this new frontier toward
      becoming a treatment in mainstream medicine.

PMID- 17018122
TI  - Drug-minimization or tolerance-promoting strategies in human kidney
      transplantation: is Campath-1H the way to follow?

PMID- 17018123
TI  - Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus
      immunosuppression for renal transplantation.
AB  - Campath-1H (alemtuzumab) induction was used for renal transplantation in
      combination with sirolimus as immunosuppression. We previously reported a high
      (28%) rate of early rejection with this regimen, and now report 3-year outcomes.
      Twenty-nine patients were recipients of either deceased donor or non-HLA (Human
      Leukocyte Antigen) identical living donor primary renal allografts. Clinical
      parameters including infection, malignancy, kidney function, and kidney histology
      were followed prospectively for 3 years. Three-year cumulative graft and patient
      survival were 96% and 100%, respectively. Twenty patients were maintained on
      steroid-free immunosuppressive regimens, and 15 patients were maintained on
      monotherapy for immunosuppression (12 on sirolimus). No serious infectious
      complications were observed and two patients developed basal cell skin cancer.
      The 3-year results of our initial pilot study demonstrate good graft (96%) and
      patient (100%) outcomes. Campath-1H induction has yielded a high proportion of
      patients maintained on immunosuppressive monotherapy (57%) without serious
      infectious- and no malignancy-related complications. The reported regimen yielded
      novel insights into both Campath-1H and sirolimus therapy in renal
      transplantation. Because of the higher incidence of early rejection, we recommend
      a modified strategy of immunosuppression including a brief course of a
      calcineurin inhibitor.

PMID- 17018124
TI  - Persistent cytomegalovirus infection in kidney allografts is associated with
      inferior graft function and survival.
AB  - The long-term effects of cytomegalovirus (CMV) infections on kidney allografts
      are unknown. We examined the impact of persistent intragraft CMV infection on
      long-term kidney allograft function and survival. CMV was diagnosed in 82/172
      renal transplant recipients by antigenemia test and viral cultures. Biopsies from
      48 of 82 patients taken after CMV infection and from 15 patients with no previous
      CMV infection detected were available for the immunohistochemical demonstration
      of CMV antigens and DNA hybridization in situ. Five-year follow-up data from
      these 63 patients were analysed. In 17 patients, CMV antigens and/or DNA
      persisted in the biopsy >2 months after the last positive finding in blood or
      urine. Patients with persistent intragraft CMV had reduced graft survival (P =
      0.041) and Cox regression analysis showed persistent CMV as a risk factor for
      reduced graft survival (RR: 3.5). Recipients with persistent intragraft CMV had
      reduced creatinine clearance 1 and 2 years after transplantation (P = 0.007) and
      in multivariate logistic regression analyses including several potential pre- and
      posttransplant risk factors, persistent CMV was an independent risk factor for
      lower clearance at 1 and 2 years (OR: 4.4 and 4.9). Our novel findings show that
      persistent intragraft CMV infection was associated with reduced kidney allograft
      function and survival.

PMID- 17018125
TI  - The influence of obesity on short- and long-term graft and patient survival after
      renal transplantation.
AB  - To determine short- and long-term patient and graft survival in obese [body mass
      index (BMI) >or= 30 kg/m(2)] and nonobese (BMI < 30 kg/m(2)) renal transplant
      patients we retrospectively analyzed our national-database. Patients 18 years or
      older receiving a primary transplant after 1993 were included. A total of 1,871
      patients were included in the nonobese group and 196 in the obese group. In the
      obese group there were significantly more females (52% vs. 38.6%, P < 0.01) and
      patients were significantly older [52 years (43-59) vs. 48 years (37-58); P <
      0.05]. Patient survival and graft survival were significantly decreased in obese
      renal transplant recipients (1 and 5 year patient survival were respectively 94%
      vs. 97% and 81% vs. 89%, P < 0.01; 1 and 5 year graft survival were respectively
      86% vs. 92% and 71% vs. 80%, P < 0.01). Initial BMI was an independent predictor
      for patient death and graft failure. This large retrospective study shows that
      both graft and patient survival are significantly lower in obese renal transplant
      recipients.

PMID- 17018126
TI  - Excess risk of cancer in renal transplant patients.
AB  - Cancer data were reviewed in 488 patients who underwent renal transplantation and
      received cyclosporine at our centre from January 1985 to December 1995. Incidence
      of nonmelanoma skin cancer (NMSC) was standardized on the age and sex
      distribution of the French population. For cancer other than NMSC, we calculated
      the ratio of observed to expected numbers of cancer cases in the RT population,
      based on age- and sex-specific incidence for cancer in France. Standardized
      incidence ratios (SIR) were calculated for all cancers and for specific cancer
      types encountered. Over 4,638 patient-years of exposure, 51 (10.4%) transplant
      recipients developed a first NMSC which was significantly associated with older
      age at transplantation (P < 0.0001) and the 1991-1995 transplantation period (P =
      0.0008). Fifty-six recipients developed cancer other than NMSC over the period.
      The SIR for all cancer was 2.2 (1.5-3.0) in males and 3.0 (1.9-4.6) in females.
      The SIR for specific cancer types revealed significant excess for native kidneys
      [13.0 (5.2-26.8)] prostate cancer [3.6 (1.5-3.0)] and post-transplant
      lymphoproliferative disorder (PTLD) [9.5 (3.1-22.1)] in males, and cervical
      cancer [25.3 (9.3-55.0)], native kidneys [26.4 (5.4-77.2)] and PTLD [28.9 (9.4
      67.6)] in females. Incidence of NMSC and some types of other cancer is high in
      cyclosporine-treated patients. Optimizing monitoring practice might be useful to
      identify subjects with significant excess risk for specific types of solid
      tumours.

PMID- 17018127
TI  - The linear cutting stapler for enteric anastomosis: a new technique in pancreas
      transplantation.
AB  - The drainage of pancreatic exocrine secretions following pancreas transplantation
      is an evolving area of surgical practice. We describe a new technique applying a
      55 mm Linear Cutting Stapler (LCS) to create the duodenoenterostomy for enteric
      drainage of the pancreas transplant. Twenty simultaneous pancreas and kidney
      transplantations performed between April 2005 and March 2006 were reviewed. Using
      a prospective database and chart review, complications and outcome related to the
      new technique of exocrine drainage were described. During this 12 month period,
      19 of 20 consecutive simultaneous pancreas and kidney transplantations have been
      performed using the linear cutting stapler techinque. No complications relating
      to the enteric anastomosis have been demonstrated. In our initial experience, use
      of the LCS is both safe and easy to perform.

PMID- 17018128
TI  - Recombinant human erythropoietin protects the liver from hepatic ischemia
      reperfusion injury in the rat.
AB  - Recently, erythropoietin was shown to have both hematopoietic as well as tissue
      protective properties. Erythropoietin (EPO) had a protective effect in animal
      models of cerebral ischemia, mechanical trauma of the nervous system, myocardial
      infarction, and ischemia-reperfusion (I/R) injury of the kidney. It is not known
      whether EPO protects the liver against I/R injury. Using a rat model of liver I/R
      injury, we aimed to determine the effect of the administration of human
      recombinant erythropoietin (rhEPO) on liver injury. Rats were subjected to 30 min
      of liver ischemia followed by 2 h of reperfusion. When compared with the sham
      operated rats, I/R resulted in significant rises in the serum levels of aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyl
      transferase, tissue lipid peroxidation, caspase-3 activity and altered histology.
      Administration of rhEPO 5 min before ischemia was able to reduce the biochemical
      evidence of liver injury; however, this protection was not evident when rhEPO was
      administered 5 min before reperfusion. Mechanistically, early administration of
      rhEPO was able to reduce the oxidative stress and caspase-3 activation,
      suggesting the subsequent reduction of apoptosis. This study provides the first
      evidence that rhEPO causes a substantial reduction of the liver injury induced by
      I/R in the rat.

PMID- 17018129
TI  - Different mechanisms of Campath-1H-mediated depletion for CD4 and CD8 T cells in
      peripheral blood.
AB  - It is assumed that complement and noncomplement-mediated mechanisms are similarly
      responsible for Campath-1H-mediated killing of all T-cell subtypes in vivo.
      However, the differing surface expression of CD52 on T-cell subtypes suggests
      that may not be the case. The purpose of this study is to determine the extent
      and mechanism of Campath-1H-mediated elimination of different T-cell subtypes in
      peripheral blood. Whole blood or lymphocytes isolated from peripheral blood of
      healthy volunteers by Ficoll density centrifugation were incubated with Campath
      1H, with or without complement and/or serum, and the resultant T-cell elimination
      mechanisms studied. For CD4(+) T lymphocytes, 60% and 40% cell death and for
      CD8(+) T lymphocytes 23% and 77% cell death, in peripheral blood, was mediated by
      complement and noncomplement mediated mechanisms, respectively. CD4(+) T cells
      demonstrated approximately twice the amount of surface CD52 compared with CD8(+)
      T cells, consistent with primarily complement-mediated killing for CD4(+) T
      cells. Thus, peripheral blood supports differential and partial elimination of T
      cell subtypes, suggesting that the complete T-cell elimination seen in transplant
      recipients is most likely due to contribution from other lymphoid organs.

PMID- 17018130
TI  - Mesocaval stenting for therapy of portal hypertension after orthotopic liver
      transplantation.
AB  - A 20-year-old patient underwent liver transplantation (LT) because of chronic
      hepatitis-associated cirrhosis. After transplantation, the patient developed
      partial portal vein thrombosis without deterioration of liver function. However,
      in the long-term follow-up, the patient developed refractory portal hypertension
      with recurrent episodes of severe upper gastrointestinal bleeding. Extensive
      nonoperative treatment including multiple esophageal ligatures and sclerotherapy
      was not successful. Thus, the patient had to be treated surgically with a
      mesocaval H-shunt. Pathophysiology, therapy and prognosis of this rare
      complication after LT are discussed with regard to the literature.

PMID- 17018131
TI  - Successful percutaneous pulse spray thrombolysis of extensive acute portocaval
      hemitransposition thrombosis.
AB  - We report a case of extensive acute thrombosis of portal vein and cava in a
      portocaval hemitransposition liver graft that was treated successfully with
      percutaneous pulse spray thrombolysis through a femoral vein access. The patient
      subsequently developed descending and sigmoid colon ischemic necrosis because of
      the venous thrombosis necessitating emergency colon resection. The patient had
      prolonged postoperative intensive care stay, but was eventually discharged in a
      good condition with normal liver function. Three month follow up demonstrated
      persistent normalization of hepatic function and normal duplex ultrasound.

PMID- 17018132
TI  - The use of radial artery interpositional graft between recipient splenic artery
      and graft artery in living donor liver transplantation.

PMID- 17018133
TI  - Growth factors and cytokines in autologous platelet concentrate and their
      correlation to periodontal regeneration outcomes.
AB  - AIM: To determine the concentration of naturally available biologic mediators in
      autologous platelet concentrates and their correlation with periodontal
      regeneration outcomes. MATERIAL AND METHODS: In 25 patients with two intra-bony
      defects each, an autologous platelet concentrate (APC) was prepared by a
      laboratory thrombocyte apheresis technique pre-operatively. Both defects were
      treated using a bioresorbable guided tissue regeneration-membrane in combination
      with tricalciumphosphate (TCP). In the test defect, APC was additionally applied.
      In the APC, platelets were counted and the levels of growth factors and cytokines
      were determined by ELISA. Correlations between the platelet counts or the growth
      factor/cytokine levels and the potential clinical and radiographic regeneration
      outcomes due to APC were calculated after 3, 6, and 12 months. RESULTS: The APC
      contained 2.2 x 10(6) platelets/mul, which was 7.9 times more than in the venous
      blood. Transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-I
      (IGF-I), platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, vascular
      endothelial growth factor (VEGF), and epidermal growth factor (EGF) were found in
      the APC, whereas interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha
      (TNFalpha), IL-4, and IL-10 were not detectable. The regression analysis showed a
      weak correlation between the platelet counts or the growth factor levels and the
      clinical and radiographic regeneration outcomes (r2<or=0.4). CONCLUSION:
      Autologous platelet concentrate contains relatively high concentrations of PDGF
      AB, PDGF-BB, TGF-beta1, and IGF-I, but their potential influence on periodontal
      regeneration remains unclear.

PMID- 17018134
TI  - Inhibition of PP2A by LIS1 increases HIV-1 gene expression.
AB  - BACKGROUND: Lissencephaly is a severe brain malformation in part caused by
      mutations in the LIS1 gene. LIS1 interacts with microtubule-associated proteins,
      and enhances transport of microtubule fragments. Previously we showed that LIS1
      interacts with HIV-1 Tat protein and that this interaction was mediated by WD40
      domains of LIS1. In the present study, we analyze the effect of LIS1 on Tat
      mediated transcription of HIV-1 LTR. RESULTS: Tat-mediated HIV-1 transcription
      was upregulated in 293 cells transfected with LIS1 expression vector. The WD5 but
      not the N-terminal domain of LIS1 increases Tat-dependent HIV-1 transcription.
      The effect of LIS1 was similar to the effect of okadaic acid, an inhibitor of
      protein phosphatase 2A (PP2A). We then analyzed the effect of LIS1 on the
      activity of PP2A in vitro. We show that LIS1 and its isolated WD5 domain but not
      the N-terminal domain of LIS1 blocks PP2A activity. CONCLUSION: Our results show
      that inhibition of PP2A by LIS1 induces HIV-1 transcription. Our results also
      point to a possibility that LIS1 might function in the cells as a yet
      unrecognized regulatory subunit of PP2A.

PMID- 17018135
TI  - The discovery of endogenous retroviruses.
AB  - When endogenous retroviruses (ERV) were discovered in the late 1960s, the
      Mendelian inheritance of retroviral genomes by their hosts was an entirely new
      concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was
      not generally accepted, and reverse transcriptase was yet to be discovered.
      Nonetheless, the evidence that we accrued in the pre-molecular era has stood the
      test of time, and our hypothesis on ERV, which one reviewer described as
      'impossible', proved to be correct. Here I recount some of the key observations
      in birds and mammals that led to the discovery of ERV, and comment on their
      evolution, cross-species dispersion, and what remains to be elucidated.

PMID- 17018136
TI  - Changes in liver mitochondrial plasticity induced by brain tumor.
AB  - BACKGROUND: Accumulating data suggest that liver is a major target organ of
      systemic effects observed in the presence of a cancer. In this study, we
      investigated the consequences of the presence of chemically induced brain tumors
      in rats on biophysical parameters accounting for the dynamics of water in liver
      mitochondria. METHODS: Tumors of the central nervous system were induced by
      intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the
      19th day of gestation. The mitochondrial crude fraction was isolated from the
      liver of each animal and the dynamic parameters of total water and its
      macromolecule-associated fraction (structured water, H2Ost) were calculated from
      Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a
      malignant brain tumor induced a loss of water structural order that implicated
      changes in the physical properties of the hydration shells of liver mitochondria
      macromolecules. This feature was linked to an increase in the membrane
      cholesterol content, a way to limit water penetration into the bilayer and then
      to reduce membrane permeability. As expected, these alterations in mitochondrial
      plasticity affected ionic exchanges and led to abnormal features of mitochondrial
      biogenesis and caspase activation. CONCLUSION: This study enlightens the
      sensitivity of the structured water phase in the liver mitochondria machinery to
      external conditions such as tumor development at a distant site. The profound
      metabolic and functional changes led to abnormal features of ion transport,
      mitochondrial biogenesis and caspase activation.

PMID- 17018137
TI  - Steroidogenic acute regulatory protein (StAR): evidence of gonadotropin-induced
      steroidogenesis in Alzheimer disease.
AB  - BACKGROUND: Alzheimer disease (AD) is clinically characterized by progressive
      memory loss, impairments in behavior, language and visual-spatial skills and
      ultimately, death. Epidemiological data reporting the predisposition of women to
      AD has led to a number of lines of evidence suggesting that age-related changes
      in hormones of the hypothalamic-pituitary-gonadal (HPG) axis following
      reproductive senescence, may contribute to the etiology of AD. Recent studies
      from our group and others have reported not only increases in circulating
      gonadotropins, namely luteinizing hormone (LH) in individuals with AD compared
      with control individuals, but also significant elevations of LH in vulnerable
      neuronal populations in individuals with AD compared to control cases as well as
      the highest density of gonadotropin receptors in the brain are found within the
      hippocampus, a region devastated in AD. However, while LH is higher in AD
      patients, the downstream consequences of this are incompletely understood. To
      begin to examine this issue, here, we examined the expression levels of
      steroidogenic acute regulatory (StAR) protein, which regulates the first key
      event in steroidogenesis, namely, the transport of cholesterol into the
      mitochondria, and is regulated by LH through the cyclic AMP second messenger
      pathway, in AD and control brain tissue. RESULTS: Our data revealed that StAR
      protein was markedly increased in both the cytoplasm of hippocampal pyramidal
      neurons as well as in the cytoplasm of other non-neuronal cell types from AD
      brains when compared with age-matched controls. Importantly, and suggestive of a
      direct mechanistic link, StAR protein expression in AD brains colocalized with LH
      receptor expression. CONCLUSION: Therefore, our findings suggest that LH is not
      only able to bind to its receptor and induce potentially pathogenic signaling in
      AD, but also that steroidogenic pathways regulated by LH may play a role in AD.

PMID- 17018138
TI  - Detection and identification of human Plasmodium species with real-time
      quantitative nucleic acid sequence-based amplification.
AB  - BACKGROUND: Decisions concerning malaria treatment depend on species
      identification causing disease. Microscopy is most frequently used, but at low
      parasitaemia (<20 parasites/mul) the technique becomes less sensitive and time
      consuming. Rapid diagnostic tests based on Plasmodium antigen detection do often
      not allow for species discrimination as microscopy does, but also become
      insensitive at <100 parasites/microl. METHODS: This paper reports the development
      of a sensitive and specific real-time Quantitative Nucleic Acid Sequence Based
      Amplification (real-time QT-NASBA) assays, based on the small-subunit 18S rRNA
      gene, to identify the four human Plasmodium species. RESULTS: The lower detection
      limit of the assay is 100-1000 molecules in vitro RNA for all species, which
      corresponds to 0.01-0.1 parasite per diagnostic sample (i.e. 50 microl of
      processed blood). The real-time QT-NASBA was further evaluated using 79 clinical
      samples from malaria patients: i.e. 11 Plasmodium. falciparum, 37 Plasmodium
      vivax, seven Plasmodium malariae, four Plasmodium ovale and 20 mixed infections.
      The initial diagnosis of 69 out of the 79 samples was confirmed with the
      developed real-time QT-NASBA. Re-analysis of seven available original slides
      resolved five mismatches. Three of those were initially identified as P. malariae
      mono-infection, but after re-reading the slides P. falciparum was found,
      confirming the real-time QT-NASBA result. The other two slides were of poor
      quality not allowing true species identification. The remaining five discordant
      results could not be explained by microscopy, but may be due to extreme low
      numbers of parasites present in the samples. In addition, 12 Plasmodium berghei
      isolates from mice and 20 blood samples from healthy donors did not show any
      reaction in the assay. CONCLUSION: Real-time QT-NASBA is a very sensitive and
      specific technique with a detection limit of 0.1 Plasmodium parasite per
      diagnostic sample (50 microl of blood) and can be used for the detection,
      identification and quantitative measurement of low parasitaemia of Plasmodium
      species, thus making it an effective tool for diagnostic purposes and useful for
      epidemiological and drug studies.

PMID- 17018139
TI  - No association of DRD2, DRD3, and tyrosine hydroxylase gene polymorphisms with
      personality traits in the Japanese population.
AB  - BACKGROUND: Dopamine D2 receptor (DRD2) and dopamine D3 receptor (DRD3) genes
      could be candidates for personality-related genes considering their
      pharmacological profiles or structures. However, a limited number of studies have
      investigated the association between these genes and personality traits. In the
      present study, we investigated the DRD2, DRD3, and tyrosine hydroxylase (TH)
      genes in relation to personality traits in the Japanese population. Epistasis
      (gene-gene interaction) among the genes was extensively analyzed, in addition to
      the analysis based on each gene. METHODS: The -241A/G, -141C Ins/Del, and
      Ser311Cys polymorphisms in the DRD2 gene, the Ser9Gly polymorphism of the DRD3
      gene, and the Val81Met and PstI site polymorphisms in the TH gene were genotyped
      in 257 healthy Japanese subjects. Personality traits were evaluated by using the
      Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety
      Inventory (STAI). The associations between gene polymorphisms and the scores for
      NEO PI-R or Trait Anxiety of STAI were statistically analyzed by one-way analysis
      of covariance (ANCOVA) adjusting sex and age. Epistasis was assessed using two
      way ANCOVA between the polymorphisms of independent two genes. RESULTS: In the
      analysis based on each gene, trends for association were observed between State
      Anxiety and the DRD2 -141C Ins/Del polymorphism (p = 0.031, uncorrected), and
      between Trait Anxiety and the DRD2 Ser311Cys or TH PstI site polymorphism (p =
      0.048 and 0.041, respectively, uncorrected). In epistatic analysis, a trend for
      interaction was observed on the scores for Neuroticism and Trait Anxiety between
      the DRD2 -141C Ins/Del and TH Val81Met polymorphisms (p = 0.015 and 0.010,
      respectively, uncorrected). However, these differences were insignificant after
      Bonferroni correction. CONCLUSION: The present study did not provide evidence for
      the association between these dopamine-related genes and personality traits in
      the Japanese population.

PMID- 17018140
TI  - Translating global recommendations on HIV and infant feeding to the local
      context: the development of culturally sensitive counselling tools in the
      Kilimanjaro Region, Tanzania.
AB  - BACKGROUND: This paper describes the process used to develop an integrated set of
      culturally sensitive, evidence-based counselling tools (job aids) by using
      qualitative participatory research. The aim of the intervention was to contribute
      to improving infant feeding counselling services for HIV positive women in the
      Kilimanjaro Region of Tanzania. METHODS: Formative research using a combination
      of qualitative methods preceded the development of the intervention and mapped
      existing practices, perceptions and attitudes towards HIV and infant feeding
      (HIV/IF) among mothers, counsellors and community members. Intervention Mapping
      (IM) protocol guided the development of the overall intervention strategy.
      Theories of behaviour change, a review of the international HIV/IF guidelines and
      formative research findings contributed to the definition of performance and
      learning objectives. Key communication messages and colourful graphic
      illustrations related to infant feeding in the context of HIV were then developed
      and/or adapted from existing generic materials. Draft materials were field tested
      with intended audiences and subjected to stakeholder technical review. RESULTS:
      An integrated set of infant feeding counselling tools, referred to as 'job aids',
      was developed and included brochures on feeding methods that were found to be
      socially and culturally acceptable, a Question and Answer Guide for counsellors,
      a counselling card on the risk of transmission of HIV, and an infant feeding
      toolbox for demonstration. Each brochure describes the steps to ensure safer
      infant feeding using simple language and images based on local ideas and
      resources. The brochures are meant to serve as both a reference material during
      infant feeding counselling in the ongoing prevention of mother to child
      transmission (pMTCT) of HIV programme and as take home material for the mother.
      CONCLUSION: The study underscores the importance of formative research and a
      systematic theory based approach to developing an intervention aimed at improving
      counselling and changing customary feeding practices. The identification of
      perceived barriers and facilitators for change contributed to developing the key
      counselling messages and graphics, reflecting the socio-economic reality,
      cultural beliefs and norms of mothers and their significant others.

PMID- 17018141
TI  - Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic
      effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast
      cancer cells.
AB  - Histone deacetylase inhibitors (HDACIs) have been shown to induce apoptotic and
      autophagic cell death in vitro and in vivo. The molecular mechanisms that
      underlie these cytotoxic effects are not yet clearly understood. Recently, HDACIs
      were shown to induce Akt dephosphorylation by disrupting HDAC-protein phosphatase
      1 (PP1) complexes. This disruption results in the increased association of PP1
      with Akt, resulting in the dephosphorylation and consequent inactivation of the
      kinase. Akt enhances cellular survival through the phosphorylation-dependent
      inhibition of several pro-apoptotic proteins. Akt is an important negative
      regulator of GSK3beta, a kinase that has been shown to regulate apoptosis in
      response to various stimuli. In the present study, we investigated the role of
      GSK3beta in mediating the cytotoxic effects in MCF-7 breast cancer cells treated
      with trichostatin A (TSA), a prototype HDACI. We show that TSA induces Akt
      dephosphorylation in a PP1-dependent manner, resulting in activation of GSK3beta
      in MCF-7 cells. Similarly, knockdown of HDAC1 and-2 by small interfering RNA
      (siRNA) resulted in the dephosphorylation of Akt and GSK3beta. Selective
      inhibition of GSK3beta attenuated TSA induced cytotoxicity and resulted in
      enhanced proliferation following drug removal. Our findings identify GSK3beta as
      an important mediator of TSA-induced cytotoxicity in MCF-7 breast cancer cells.

PMID- 17018143
TI  - Grouping Gene Ontology terms to improve the assessment of gene set enrichment in
      microarray data.
AB  - BACKGROUND: Gene Ontology (GO) terms are often used to assess the results of
      microarray experiments. The most common way to do this is to perform Fisher's
      exact tests to find GO terms which are over-represented amongst the genes
      declared to be differentially expressed in the analysis of the microarray
      experiment. However, due to the high degree of dependence between GO terms,
      statistical testing is conservative, and interpretation is difficult. RESULTS: We
      propose testing groups of GO terms rather than individual terms, to increase
      statistical power, reduce dependence between tests and improve the interpretation
      of results. We use the publicly available package POSOC to group the terms. Our
      method finds groups of GO terms significantly over-represented amongst
      differentially expressed genes which are not found by Fisher's tests on
      individual GO terms. CONCLUSION: Grouping Gene Ontology terms improves the
      interpretation of gene set enrichment for microarray data.

PMID- 17018142
TI  - Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is
      variable and asymmetric.
AB  - BACKGROUND: Glaucoma is a chronic neurodegenerative disease of the retina,
      characterized by the degeneration of axons in the optic nerve and retinal
      ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma
      and are an important model system to study the molecular mechanisms underlying
      this disease and novel therapeutic interventions designed to attenuate the loss
      of retinal ganglion cells. Although the genetics of this disease in these mice
      are well characterized, the etiology of its progression, particularly with
      respect to retinal degeneration, is not. We have used two separate labeling
      techniques, post-mortem DiI labeling of axons and ganglion cell-specific
      expression of the betaGeo reporter gene, to evaluate the time course of optic
      nerve degeneration and ganglion cell loss, respectively, in aging mice. RESULTS:
      Optic nerve degeneration, characterized by axon loss and gliosis is first
      apparent in mice between 8 and 9 months of age. Degeneration appears to follow a
      retrograde course with axons dying from their proximal ends toward the globe.
      Although nerve damage is typically bilateral, the progression of disease is
      asymmetric between the eyes of individual mice. Some nerves also exhibit focal
      preservation of tracts of axons generally in the nasal peripheral region.
      Ganglion cell loss, as a function of the loss of betaGeo expression, is evident
      in some mice between 8 and 10 months of age and is prevalent in the majority of
      mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells
      throughout the retina, but many younger mice exhibit focal loss of cells in
      sectors extending from the optic nerve head to the retinal periphery. Similar to
      what we observe in the optic nerves, ganglion cell loss is often asymmetric
      between the eyes of the same animal. CONCLUSION: A comparison of the data
      collected from the two cohorts of mice used for this study suggests that the
      initial site of damage in this disease is to the axons in the optic nerve,
      followed by the subsequent death of the ganglion cell soma.

PMID- 17018144
TI  - MICA: desktop software for comprehensive searching of DNA databases.
AB  - BACKGROUND: Molecular biologists work with DNA databases that often include
      entire genomes. A common requirement is to search a DNA database to find exact
      matches for a nondegenerate or partially degenerate query. The software programs
      available for such purposes are normally designed to run on remote servers, but
      an appealing alternative is to work with DNA databases stored on local computers.
      We describe a desktop software program termed MICA (K-Mer Indexing with Compact
      Arrays) that allows large DNA databases to be searched efficiently using very
      little memory. RESULTS: MICA rapidly indexes a DNA database. On a Macintosh G5
      computer, the complete human genome could be indexed in about 5 minutes. The
      indexing algorithm recognizes all 15 characters of the DNA alphabet and fully
      captures the information in any DNA sequence, yet for a typical sequence of
      length L, the index occupies only about 2L bytes. The index can be searched to
      return a complete list of exact matches for a nondegenerate or partially
      degenerate query of any length. A typical search of a long DNA sequence involves
      reading only a small fraction of the index into memory. As a result, searches are
      fast even when the available RAM is limited. CONCLUSION: MICA is suitable as a
      search engine for desktop DNA analysis software.

PMID- 17018145
TI  - Mathematical modeling of tumor therapy with oncolytic viruses: effects of
      parametric heterogeneity on cell dynamics.
AB  - BACKGROUND: One of the mechanisms that ensure cancer robustness is tumor
      heterogeneity, and its effects on tumor cells dynamics have to be taken into
      account when studying cancer progression. There is no unifying theoretical
      framework in mathematical modeling of carcinogenesis that would account for
      parametric heterogeneity. RESULTS: Here we formulate a modeling approach that
      naturally takes stock of inherent cancer cell heterogeneity and illustrate it
      with a model of interaction between a tumor and an oncolytic virus. We show that
      several phenomena that are absent in homogeneous models, such as cancer
      recurrence, tumor dormancy, and others, appear in heterogeneous setting. We also
      demonstrate that, within the applied modeling framework, to overcome the adverse
      effect of tumor cell heterogeneity on the outcome of cancer treatment, a
      heterogeneous population of an oncolytic virus must be used. Heterogeneity in
      parameters of the model, such as tumor cell susceptibility to virus infection and
      the ability of an oncolytic virus to infect tumor cells, can lead to complex,
      irregular evolution of the tumor. Thus, quasi-chaotic behavior of the tumor-virus
      system can be caused not only by random perturbations but also by the
      heterogeneity of the tumor and the virus. CONCLUSION: The modeling approach
      described here reveals the importance of tumor cell and virus heterogeneity for
      the outcome of cancer therapy. It should be straightforward to apply these
      techniques to mathematical modeling of other types of anticancer therapy.
      REVIEWERS: Leonid Hanin (nominated by Arcady Mushegian), Natalia Komarova
      (nominated by Orly Alter), and David Krakauer.

PMID- 17018146
TI  - Defining rational hospital catchments for non-urban areas based on travel-time.
AB  - BACKGROUND: Cost containment typically involves rationalizing healthcare service
      delivery through centralization of services to achieve economies of scale.
      Hospitals are frequently the chosen site of cost containment and rationalization
      especially in rural areas. Socio-demographic and geographic characteristics make
      hospital service allocation more difficult in rural and remote regions. This
      research presents a methodology to model rational catchments or service areas
      around rural hospitals--based on travel time. RESULTS: This research employs a
      vector-based GIS network analysis to model catchments that better represent
      access to hospital-based healthcare services in British Columbia's rural and
      remote areas. The tool permits modelling of alternate scenarios in which access
      to different baskets of services (e.g. rural maternity care or ICU) are assessed.
      In addition, estimates of the percentage of population that is served--or not
      served--within specified travel times are calculated. CONCLUSION: The modelling
      tool described is useful for defining true geographical catchments around rural
      hospitals as well as modelling the percentage of the population served within
      certain time guidelines (e.g. one hour) for specific health services. It is
      potentially valuable to policy makers and health services allocation specialists.

PMID- 17018147
TI  - Ethical issues in epidemiologic research and public health practice.
AB  - A rich and growing body of literature has emerged on ethics in epidemiologic
      research and public health practice. Recent articles have included conceptual
      frameworks of public health ethics and overviews of historical developments in
      the field. Several important topics in public health ethics have also been
      highlighted. Attention to ethical issues can facilitate the effective planning,
      implementation, and growth of a variety of public health programs and research
      activities. Public health ethics is consistent with the prevention orientation of
      public health. Ethical concerns can be anticipated or identified early and
      effectively addressed through careful analysis and consultation.

PMID- 17018148
TI  - XRate: a fast prototyping, training and annotation tool for phylo-grammars.
AB  - BACKGROUND: Recent years have seen the emergence of genome annotation methods
      based on the phylo-grammar, a probabilistic model combining continuous-time
      Markov chains and stochastic grammars. Previously, phylo-grammars have required
      considerable effort to implement, limiting their adoption by computational
      biologists. RESULTS: We have developed an open source software tool, xrate, for
      working with reversible, irreversible or parametric substitution models combined
      with stochastic context-free grammars. xrate efficiently estimates maximum
      likelihood parameters and phylogenetic trees using a novel "phylo-EM" algorithm
      that we describe. The grammar is specified in an external configuration file,
      allowing users to design new grammars, estimate rate parameters from training
      data and annotate multiple sequence alignments without the need to recompile code
      from source. We have used xrate to measure codon substitution rates and predict
      protein and RNA secondary structures. CONCLUSION: Our results demonstrate that
      xrate estimates biologically meaningful rates and makes predictions whose
      accuracy is comparable to that of more specialized tools.

PMID- 17018149
TI  - The CF-CIRC study: a French collaborative study to assess the accuracy of cystic
      fibrosis diagnosis in neonatal screening.
AB  - BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding for
      the CF transmembrane conductance regulator (CFTR) protein, which acts as a
      chloride channel after activation by cyclic AMP (cAMP). Newborn screening
      programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay,
      followed when IRT is elevated by testing for a panel of CF-causing mutations.
      Some children, however, may have persistent hypertrypsinogenemia, only one or no
      identified CFTR gene mutation, and sweat chloride concentrations close to normal
      values. In vivo demonstration of abnormal CFTR protein function would be an
      important diagnostic aid in this situation. Measurements of transepithelial nasal
      potential differences (NPD) in adults accurately characterize CFTR-related ion
      transport. The aim of the present study is to establish reference values for NPD
      measurements for healthy children and those with CF aged 3 months to 3 years, the
      age range of most difficult-to-diagnose patients with suspected CF. The ultimate
      goal of our study is to validate NPD testing as a diagnostic tool for children
      with borderline results in neonatal screening. METHODS/DESIGN: We adapted the
      standard NPD protocol for young children, designed a special catheter for them,
      used a slower perfusion rate, and shortened the protocol to include only
      measurement of basal PD, transepithelial sodium (Na+) transport in response to
      the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl-) secretion
      in response to isoproterenol, a beta-agonist in a Cl- free solution. The study
      will include 20 children with CF and 20 healthy control children. CF children
      will be included only if they carry 2 CF-causing mutations in the CFTR gene or
      have sweat chloride concentrations > 60 mEq/L or both. The healthy children will
      be recruited among the siblings of the CF patients, after verification that they
      do not carry the familial mutation. DISCUSSION: A preliminary study of 3 adult
      control subjects and 4 children older than 12 years with CF verified that the new
      protocol was well tolerated and produced NPD measurements that did not differ
      significantly from those obtained with the standard protocol. This preliminary
      study will provide a basis for interpreting NPD measurements in patients with
      suspected CF after neonatal screening. Earlier definitive diagnosis should
      alleviate parental distress and allow earlier therapeutic intervention and
      genetic counseling.

PMID- 17018150
TI  - Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on
      cellular survival upon oxidative stress.
AB  - BACKGROUND: Oxidative damage to mitochondrial DNA has been implicated as a
      causative factor in a wide variety of degenerative diseases, aging and cancer.
      The modified guanine, 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine)
      is one of the major oxidized bases generated in DNA by reactive oxygen species
      and has gained most of the attention in recent years as a marker of oxidative DNA
      injury and its suspected role in the initiation of carcinogenesis. 8
      hydroxyguanine is removed by hOgg1, a DNA glycosylase/AP lyase involved in the
      base excision repair pathway. METHODS: We over-expressed wild type and R229Q
      mutant hOGG1 in the nucleus and mitochondria of cells lacking mitochondrial hOGG1
      expression through an expression vector containing nuclear and mitochondrial
      targeting sequence respectively. We used quantitative real time PCR to analyze
      mtDNA integrity after exposure to oxidative damaging agents, in cells transfected
      with or without mitochondrially-targeted mutant hogg1. RESULT: Over-expression of
      wild type hOgg1 in both nucleus and mitochondria resulted in increased cellular
      survival when compared to vector or mutant over-expression of hOGG1.
      Interestingly, mitochondrially-targeted mutant hogg1 resulted in more cell death
      than nuclear targeted mutant hogg1 upon exposure of cells to oxidative damage.
      Additional we examined mitochondrial DNA integrity after oxidative damage
      exposure using real-time quantitative PCR. The presence of mutant hogg1 in the
      mitochondria resulted in reduced mitochondrial DNA integrity when compared to the
      wild type. Our work indicates that the R229Q hOGG1 mutation failed to protect
      cells from oxidative damage and that such mutations in cancer may be more
      detrimental to cellular survival when present in the mitochondria than in the
      nucleus. CONCLUSION: These findings suggest that deficiencies in hOGG1,
      especially in the mitochondria may lead to reduced mitochondrial DNA integrity,
      consequently resulting in decreased cell viability.

PMID- 17018151
TI  - Design of a combinatorial DNA microarray for protein-DNA interaction studies.
AB  - BACKGROUND: Discovery of precise specificity of transcription factors is an
      important step on the way to understanding the complex mechanisms of gene
      regulation in eukaryotes. Recently, double-stranded protein-binding microarrays
      were developed as a potentially scalable approach to tackle transcription factor
      binding site identification. RESULTS: Here we present an algorithmic approach to
      experimental design of a microarray that allows for testing full specificity of a
      transcription factor binding to all possible DNA binding sites of a given length,
      with optimally efficient use of the array. This design is universal, works for
      any factor that binds a sequence motif and is not species-specific. Furthermore,
      simulation results show that data produced with the designed arrays is easier to
      analyze and would result in more precise identification of binding sites.
      CONCLUSION: In this study, we present a design of a double stranded DNA
      microarray for protein-DNA interaction studies and show that our algorithm allows
      optimally efficient use of the arrays for this purpose. We believe such a design
      will prove useful for transcription factor binding site identification and other
      biological problems.

PMID- 17018152
TI  - Gay/Lesbian sexual orientation increases risk for cigarette smoking and heavy
      drinking among members of a large Northern California health plan.
AB  - BACKGROUND AND SIGNIFICANCE: Tobacco and alcohol use and related morbidity and
      mortality are critical public health problems. Results of several, but not all,
      studies suggest that lesbians and gay men are at elevated risk for smoking
      tobacco and alcohol misuse. METHODS: Data from random sample general health
      surveys of adult members of a large Northern California Health Plan conducted in
      1999 and 2002 were analyzed using gender-based multivariate logistic regression
      models to assess whether lesbians (n = 210) and gay men (n = 331) aged 20-65 were
      more likely than similarly aged heterosexual women (n = 12,188) and men (n =
      9342) to be smokers and heavy drinkers. RESULTS: After adjusting for age,
      race/ethnicity, education, and survey year, lesbians were significantly more
      likely than heterosexual women to be heavy drinkers (OR 2.14, 95% CI 1.08, 4.23)
      and current smokers (OR 1.60, 95% CI 1.02, 2.51). Among men, gays were
      significantly more likely than heterosexuals to be current smokers (OR 2.40, 95%
      CI 1.75, 3.30), with borderline significant increased risk for heavy drinking (OR
      1.54, 95% CI 0.96, 2.45). CONCLUSION: Lesbians and gay men may be at increased
      risk for morbidity and mortality due to higher levels of cigarette and alcohol
      use. More population-based research is needed to understand the nature of
      substance use in these communities so that appropriate interventions can be
      developed.

PMID- 17018153
TI  - Association of socio-economic status with diabetes prevalence and utilization of
      diabetes care services.
AB  - BACKGROUND: Low income appears to be associated with a higher prevalence of
      diabetes and diabetes related complications, however, little is known about how
      income influences access to diabetes care. The objective of the present study was
      to determine whether income is associated with referral to a diabetes centre
      within a universal health care system. METHODS: Data on referral for diabetes
      care, diabetes prevalence and median household income were obtained from a
      regional Diabetes Education Centre (DEC) database, the Canadian National Diabetes
      Surveillance System (NDSS) and the 2001 Canadian Census respectively. Diabetes
      rate per capita, referral rate per capita and proportion with diabetes referred
      was determined for census dissemination areas. We used Chi square analyses to
      determine if diabetes prevalence or population rates of referral differed across
      income quintiles, and Poisson regression to model diabetes rate and referral rate
      in relation to income while controlling for education and age. RESULTS: There was
      a significant gradient in both diabetes prevalence (chi2 = 743.72, p < 0.0005)
      and population rates of referral (chi2 = 168.435, p < 0.0005) across income
      quintiles, with the lowest income quintiles having the highest rates of diabetes
      and referral to the DEC. Referral rate among those with diabetes, however, was
      uniform across income quintiles. Controlling for age and education, Poisson
      regression models confirmed a significant socio-economic gradient in diabetes
      prevalence and population rates of referral. CONCLUSION: Low income is associated
      with a higher prevalence of diabetes and a higher population rate of referral to
      this regional DEC. After accounting for diabetes prevalence, however, the equal
      proportions referred to the DEC across income groups suggest that there is no
      access bias based on income.

PMID- 17018154
TI  - Assessing the feasibility of harm reduction services for MSM: the late night
      breakfast buffet study.
AB  - BACKGROUND: Despite the leveling off in new HIV infections among men who have sex
      with men (MSM) in San Francisco, new evidence suggests that many recent HIV
      infections are linked with the use of Methamphetamine (MA). Among anonymous HIV
      testers in San Francisco, HIV incidence among MA users was 6.3% compared to 2.1%
      among non-MA users. Of particular concern for prevention programs are frequent
      users and HIV positive men who use MA. These MSM pose a particular challenge to
      HIV prevention efforts due to the need to reach them during very late night
      hours. METHODS: The purpose of the Late Night Breakfast Buffet (LNBB) was to
      determine the feasibility and uptake of harm reduction services by a late night
      population of MSM. The "buffet" of services included: needle exchange, harm
      reduction information, oral HIV testing, and urine based sexually transmitted
      infection (STI) testing accompanied by counseling and consent procedures. The
      study had two components: harm reduction outreach and a behavioral survey. For 4
      months during 2004, we provided van-based harm reduction services in three
      neighborhoods in San Francisco from 1-5 a.m. for anyone out late at night. We
      also administered a behavioral risk and service utilization survey among MSM.
      RESULTS: We exchanged 2000 needles in 233 needle exchange visits, distributed
      4500 condoms/lubricants and provided 21 HIV tests and 12 STI tests. Fifty-five
      MSM enrolled in the study component. The study population of MSM was
      characterized by low levels of income and education whose ages ranged from 18-55.
      Seventy-eight percent used MA in the last 3 months; almost 25% used MA every day
      in the same time frame. Of the 65% who ever injected, 97% injected MA and 13%
      injected it several times a day. MA and alcohol were strong influences in the
      majority of unprotected sexual encounters among both HIV negative and HIV
      positive MSM. CONCLUSION: We reached a disenfranchised population of MA-using MSM
      who are at risk for acquiring or transmitting HIV infection through multiple high
      risk behaviors, and we established the feasibility and acceptability of late
      night harm reduction for MSM and MSM who inject drugs.

PMID- 17018155
TI  - Post-radiation sarcoma of the neck treated with re-irradiation followed by wide
      excision.
AB  - BACKGROUND: Post-radiation sarcoma (PRS) is an uncommon disease manifesting as
      sarcoma in a previously irradiated field, usually with a latent period of 5 years
      or more. Literature is limited to small series. Optimal management of this
      disease is unclear. Positive margins are common following attempted curative
      surgery and outcomes are poor. Radiotherapy is hardly used and its effect on PRS
      is not known. We described a case of PRS treated with preoperative radiotherapy
      followed by margin-negative wide excision. CASE PRESENTATION: The 59-year-old
      patient presented with a mass in the left supraclavicular fossa and numbness in
      the arm, six years following radical irradiation of the head and neck for
      nasopharyngeal carcinoma. Open biopsy showed pleomorphic spindle cell sarcoma.
      She was treated with pre-operative hyperfractionated radiotherapy followed by
      margin-negative wide excision and nerve grafting. Cumulative radiation dose to
      the supraclavicular fossa was 98 Gy. Histological examination of the post
      irradiation tumor specimens showed evidence of significant tumor response to re
      irradiation. The patient remained free of disease five years after surgery with
      excellent functional outcome. CONCLUSION: Role of radiotherapy in PRS is
      uncertain. We described a case that was successfully managed with preoperative
      radiotherapy and margin-negative wide excision in terms of tumor control and
      functional outcomes. The impact of radiotherapy was demonstrated in the post
      irradiation resected specimen. Further investigation using re-irradiation and
      surgery in PRS is warranted.

PMID- 17018156
TI  - Development of an open source laboratory information management system for 2-D
      gel electrophoresis-based proteomics workflow.
AB  - BACKGROUND: In the post-genome era, most research scientists working in the field
      of proteomics are confronted with difficulties in management of large volumes of
      data, which they are required to keep in formats suitable for subsequent data
      mining. Therefore, a well-developed open source laboratory information management
      system (LIMS) should be available for their proteomics research studies. RESULTS:
      We developed an open source LIMS appropriately customized for 2-D gel
      electrophoresis-based proteomics workflow. The main features of its design are
      compactness, flexibility and connectivity to public databases. It supports the
      handling of data imported from mass spectrometry software and 2-D gel image
      analysis software. The LIMS is equipped with the same input interface for 2-D gel
      information as a clickable map on public 2DPAGE databases. The LIMS allows
      researchers to follow their own experimental procedures by reviewing the
      illustrations of 2-D gel maps and well layouts on the digestion plates and MS
      sample plates. CONCLUSION: Our new open source LIMS is now available as a basic
      model for proteome informatics, and is accessible for further improvement. We
      hope that many research scientists working in the field of proteomics will
      evaluate our LIMS and suggest ways in which it can be improved.

PMID- 17018157
TI  - Static telepathology in cancer institute of Tehran university: report of the
      first academic experience in Iran.
AB  - Telepathology is the practice of pathology, which allows quick and timely access
      to an expert opinion at a distance. We analyzed our new experience in cancer
      Institute of Tehran University of Medical Sciences with the iPath telepathology
      server of Basel University. One hundred sixty one cases in a period of 32 months
      were consulted. These cases received for second evaluation but the definite
      diagnosis could not be made in this centre. The number of images per case ranged
      from 3 to 32 (mean: 8). Except one case all cases were evaluated by consultants.
      Definite final diagnosis was achieved in 88/160 (54.7%). Recommendations for
      further evaluation were offered in 42/160 cases (26%). Major discrepancies were
      encountered in 30/160 cases (19%). Thirty-nine of the cases (24.3%) were reported
      within 1 day. The rate of achieving final diagnosis was higher in histological
      group rather than cytological ones. Increase in number of H&E images had no
      significant effect on achieving a definite final diagnosis. The rate of achieving
      final diagnosis in this study is much lower than other similar studies, which
      could be due to inappropriate sampling images, a potential cause of misdiagnosis
      in static telepathology. The other possible reason is that all of the cases in
      this study were problematic cases that a definite diagnosis could not be made for
      them even in primary consultation. The mean time for achieving a final diagnosis
      was also more than other studies, which could be for the reasons mentioned above.

PMID- 17018158
TI  - Thoracoscopic enucleation of a large esophageal leiomyoma using a three thoracic
      ports technique.
AB  - BACKGROUND: Video assisted thoracoscopic resection of an esophageal leiomyoma
      offers distinct advantages over an open approach. Many papers have described
      various techniques of thoracoscopic resection. CASE PRESENTATION: We describe a
      32-year old man who presented with intermittent dysphagia. Imaging studies showed
      a large esophageal leiomyoma. He underwent thoracoscopic enucleation using a
      three thoracic-ports technique. CONCLUSION: Thoracoscopic enucleation can be
      technically performed using a three thoracic-ports technique.

PMID- 17018159
TI  - Helicobacter pylori genotypes identified in gastric biopsy specimens from
      Jordanian patients.
AB  - BACKGROUND: The genetic diversity of Helicobacter pylori can be analyzed at two
      different levels: the genomic variation between strains originating from
      different individuals, and the variation in bacterial populations within an
      individual host. We reported for the first time the H. pylori genotypes in
      Jordanian patients with gastrointestinal diseases. METHODS: Upper endoscopy was
      performed on 250 patients with symptoms of gastrointestinal diseases. Multiple
      gastric biopsy specimens were taken from the antrum. All the biopsies were tested
      by PCR for the H. pylori virulence genes vacA, cagA, and iceA, and 151 were
      tested by histology. RESULTS: The biopsies positive for H. pylori by PCR were
      110/250 (44%), and by histology 117/151 (77.5%), and these results were highly
      associated (P < 0.02). Analyses of virulence genes revealed that iceA2 (73.6%)
      was the predominant genotype, the vacAs2 allele was more frequently identified
      than the vacAs1 allele, while the cagA genotype was low (26.4%). The presence of
      certain genotypes might be associated with each other, but the presence of
      certain genotypes was not significantly associated with the age, or gender of the
      patient. CONCLUSION: The results illustrate the geographic nature of the genetic
      diversity of H. pylori, as the identified genotypes are similar to those reported
      in neighboring countries. This study provides a baseline data of H. pylori
      genotypes identified in gastric biopsy specimens from Jordan, serving as a
      powerful epidemiological tool for prospective investigations to better understand
      the genetic diversity of this pathogen.

PMID- 17018160
TI  - Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in
      Northern India.
AB  - BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes
      have been reported worldwide, but little is known regarding the role of these
      inherited susceptibility genes in breast cancer risk among Indian women. We
      investigated the distribution and the nature of BRCA1 and BRCA2 germline
      mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and
      140 age-matched controls. METHOD: Cases were selected with regard to early onset
      disease (< or =40 years) and family history of breast and ovarian cancer. Two
      hundred four breast cancer cases along with 140 age-matched controls were
      analyzed for mutations. All coding regions and exon-intron boundaries of the
      BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct
      sequencing of detected variants. RESULTS: In total, 18 genetic alterations were
      identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4
      and 3596del4 in exon 11) were identified in BRCA1, along with one missense
      mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10
      12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly
      three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in
      exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four
      intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one
      silent substitution (1593A>G) were identified in BRCA2. Four previously reported
      polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were
      detected in both controls and breast cancer patients. Rare BRCA1/2 sequence
      alterations were observed in 15 out of 105 (14.2%) early-onset cases without
      family history and 11.7% (4/34) breast cancer cases with family history. Of
      these, six were pathogenic protein truncating mutations. In addition, several
      variants of uncertain clinical significance were identified. Among these are two
      missense variants, one alteration of a consensus splice donor sequence, and a
      variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and
      BRCA2 mutations appear to account for a lower proportion of breast cancer
      patients at increased risk of harboring such mutations in Northern India (6/204,
      2.9%) than has been reported in other populations. However, given the limited
      extent of reported family history among these patients, the observed mutation
      frequency is not dissimilar from that reported in other cohorts of early onset
      breast cancer patients. Several of the identified mutations are unique and novel
      to Indian patients.

PMID- 17018162
TI  - Phenotypical characteristics, biochemical pathways, molecular targets and
      putative role of nitric oxide-mediated programmed cell death in Leishmania.
AB  - Nitric oxide (NO) has been demonstrated to be the principal effector molecule
      mediating intracellular killing of Leishmania, both in vitro and in vivo. We
      investigated the type of cell death process induced by NO for the intracellular
      amastigote stage of the protozoa Leishmania. Specific detection methods revealed
      a rapid and extensive cell death with morphological features of apoptosis in
      axenic amastigotes exposed to NO donors, in intracellular amastigotes inside in
      vitro - activated mouse macrophages and also in activated macrophages of
      regressive lesions in a leishmaniasis-resistant mouse model. We extended our
      investigations to the dog, a natural host-reservoir of Leishmania parasites, by
      demonstrating that co-incubation of infected macrophages with autologous
      lymphocytes derived from dogs immunised with purified excreted-secreted antigens
      of Leishmania resulted in a significant NO-mediated apoptotic cell death of
      intracellular amastigotes. From the biochemical point of view, NO-mediated
      Leishmania amastigotes apoptosis did not seem to be controlled by caspase
      activity as indicated by the lack of effect of cell permeable inhibitors of
      caspases and cysteine proteases, in contrast to specific proteasome inhibitors,
      such as lactacystin or calpain inhibitor I. Moreover, addition of the products of
      two NO molecular targets, cis-aconitase and glyceraldehyde-3-phosphate
      dehydrogenase, also had an inhibitory effect on the cell death induced by NO.
      Interestingly, activities of these two enzymes plus 6-phosphogluconate
      dehydrogenase, parasitic enzymes involved in both glycolysis and respiration
      processes, are overexpressed in amastigotes selected for their NO resistance.
      This review focuses on cell death of the intracellular stage of the pathogen
      Leishmania induced by nitrogen oxides and gives particular attention to the
      biochemical pathways and the molecular targets potentially involved. Questions
      about the role of Leishmania amastigotes NO-mediated apoptosis in the overall
      infection process are raised and discussed.

PMID- 17018161
TI  - Internet-based monitoring of influenza-like illness (ILI) in the general
      population of the Netherlands during the 2003-2004 influenza season.
AB  - BACKGROUND: An internet-based survey of influenza-like illness (ILI)--the Great
      Influenza Survey or GIS--was launched in the Netherlands in the 2003-2004
      influenza season. The aim of the present study was to validate the
      representativeness of the GIS population and to compare the GIS data with the
      official ILI data obtained by Dutch GPs participating in the Dutch Sentinel
      Practice Network. METHOD: Direct mailings to schools and universities, and
      repeated interviews on television and radio, and in newspapers were used to
      kindle the enthusiasm of a broad section of the public for GIS. Strict
      symptomatic criteria for ILI were formulated with the assistance of expert
      institutes and only participants who responded at least five times to weekly e
      mails asking them about possible ILI symptoms were included in the survey.
      Validation of GIS was done at different levels: 1) some key demographic (age
      distribution) and public health statistics (prevalence of asthma and diabetes,
      and influenza vaccination rates) for the Dutch population were compared with
      corresponding figures calculated from GIS; 2) the ILI rates in GIS were compared
      with the ILI consultation rates reported by GPs participating in the Dutch
      Sentinel Practice Network. RESULTS: 13,300 persons (53% of total responders),
      replied at least five times to weekly e-mails and were included in the survey. As
      expected, there was a marked under-representation of the age groups 0-10 years
      and 81->90 years in the GIS population, although the similarities were remarkable
      for most other age groups, albeit that the age groups between 21 and 70 years
      were slightly overrepresented. There were striking similarities between GIS and
      the Dutch population with regard to the prevalence of asthma (6.4% vs. 6.9%) and
      the influenza vaccination rates, and to a lesser degree for diabetes (2.4% vs.
      3.5%). The vaccination rates in patients with asthma or diabetes, and persons
      older than 65 years were 68%, 85%, and 85% respectively in GIS, while the
      corresponding percentages in the Dutch population were 73%, 85% and 87%. There
      was also a marked similarity between the seasonal course of ILI measured by GIS
      and the GPs. Although the ILI rate in GIS was about 10 times higher, the curves
      followed an almost similar pattern, with peak incidences occurring in the same
      week. CONCLUSION: The current study demonstrates that recruitment of a high
      number of persons willing to participate in on-line health surveillance is
      feasible. The information gathered proved to be reliable, as it paralleled the
      information obtained via an undisputed route. We believe that the interactive
      nature of GIS and the appealing subject were keys to its success.

PMID- 17018163
TI  - The archaeology of apoptosis.
AB  - Human death has been recognised as a significant personal and social event for
      many thousands of years, and classical archaeologists have revealed the changing
      complexity of rituals associated with it. The study of cell death, however, is a
      much more recent event, although many of the molecular pathways involved have now
      been identified, at least in mammalian systems. In studying the loss of cells,
      the use of the term 'death' is, perhaps, not altogether appropriate both since it
      carries the cultural resonance associated with bodily death, and because we do
      not study cell death itself, but rather the processes that lead up to it.
      Mammalian cell death processes are complex and involve a dynamic equilibrium
      between death promoting and death inhibiting factors, suggesting that some
      components of death pathways may have a paradoxical survival function. Since
      parasites must survive an often hostile environment, they may be a useful model
      to study whether component molecules of mammalian death pathways originally
      formed modules of parasite survival strategies, and whether survival and death
      pathways coevolved.

PMID- 17018164
TI  - Apoptosis-like death as a feature of malaria infection in mosquitoes.
AB  - Malaria parasites of the genus Plasmodium make a hazardous journey through their
      mosquito vectors. The majority die in the process, many as a result of the action
      of mosquito defence mechanisms. The mosquito too is not unscathed by the
      encounter with these parasites. Tissue damage occurs as a result of mid-gut
      invasion and reproductive fitness is lost when many developing ovarian follicles
      are resorbed. Here we discuss some of the mechanisms that are involved in killing
      the parasite and in the self-defence mechanisms employed by the mosquito to
      repair the mid-gut epithelium and to manipulate resources altering the trade-off
      position that balances reproduction and survival. In all cases, cells die by
      apoptotic-like mechanisms. In the midgut cells, apoptosis-induction pathways are
      being elucidated, the molecules involved in apoptosis are being recognised and
      Drosophila homologues sought. The death of ookinetes in the mosquito mid-gut
      lumen is associated with caspase-like activity and, although homologues of
      mammalian caspases are not present in the malaria genome, other cysteine
      proteases that are potential candidates have been discussed. In the ovary,
      apoptosis of patches of follicular epithelial cells is followed by resorption of
      the developing follicle and a subsequent loss of egg production in that follicle.

PMID- 17018165
TI  - Regulation of host cell survival by intracellular Plasmodium and Theileria
      parasites.
AB  - Plasmodium and Theileria parasites are obligate intracellular protozoa of the
      phylum Apicomplexa. Theileria infection of bovine leukocytes induces
      transformation of host cells and infected leukocytes can be kept indefinitely in
      culture. Theileria-dependent host cell transformation has been the subject of
      interest for many years and the molecular basis of this unique phenomenon is
      quite well understood. The equivalent life cycle stage of Plasmodium is the
      infection of mammalian hepatocytes, where parasites reside for 2-7 days depending
      on the species. Some of the molecular details of parasite-host interactions in P.
      berghei-infected hepatocytes have emerged only very recently. Similar to what has
      been shown for Theileria-infected leukocytes these data suggest that malaria
      parasites within hepatocytes also protect their host cell from programmed cell
      death. However, the strategies employed to inhibit host cell apoptotic pathways
      appear to be different to those used by Theileria. This review discusses
      similarities and differences at the molecular level of Plasmodium- and Theileria
      induced regulation of the host cell survival machinery.

PMID- 17018166
TI  - Neutrophils, apoptosis and phagocytic clearance: an innate sequence of cellular
      responses regulating intramacrophagic parasite infections.
AB  - In complex organisms, apoptosis is a constitutive cell death process that is
      involved in physiological regulation of cell numbers and that can also be induced
      in the course of inflammatory and immune responses. Neutrophils are among the
      first cells recruited during inflammation. Neutrophils constitutively die by
      apoptosis at inflamed sites, and are ingested by macrophages. Recent studies
      investigated how phagocytic clearance of senescent neutrophils influences the
      survival of intracellular protozoan parasites that have been phagocytosed by, or
      have invaded phagocytes. The results indicate that neutrophil clearance plays an
      unexpected role in regulation of intramacrophagic protozoan parasite infection.

PMID- 17018167
TI  - Pro- and anti-apoptotic activities of protozoan parasites.
AB  - During infection, programmed cell death, i.e. apoptosis, is an important effector
      mechanism of innate and adaptive host responses to parasites. In addition, it
      fulfils essential functions in regulating host immunity and tissue homeostasis.
      Not surprisingly, however, adaptation of parasitic protozoa to their hosts also
      involves modulation or even exploitation of cell death in order to facilitate
      parasite survival in a hostile environment. During recent years, considerable
      progress has been made in our understanding of apoptosis during parasitic
      infections and there is now convincing evidence that apoptosis and its modulation
      by protozoan parasites has a major impact on the parasite-host interaction and on
      the pathogenesis of disease. This review updates our current knowledge on the
      diverse functions apoptosis may fulfil during infections with diverse protozoan
      parasites including apicomplexans, kinetoplastids and amoebae. Furthermore, we
      also summarize common mechanistic themes of the pro- and anti-apoptotic
      activities of protozoan parasites. The diverse and complex effects which
      parasitic protozoa exert on apoptotic cell death within the host highlight
      fascinating interactions of parasites and their hosts. Importantly, they also
      stress the importance of further investigations before the modulation of host
      cell apoptosis can be exploited to combat parasitic infections.

PMID- 17018168
TI  - Programmed cell death in African trypanosomes.
AB  - Until recently it had generally been assumed that apoptosis and other forms of
      programmed cell death evolved during evolution of the metazoans to regulate
      growth and development in these multicellular organisms. However, recent research
      is adding strength to the original phenotypic observations described almost a
      decade ago which indicated that some parasitic protozoa may have evolved a cell
      death pathway analogous to the process described as apoptosis in metazoa. Here we
      explore the implications of a programmed cell death pathway in the African tsetse
      transmitted trypanosomes.

PMID- 17018169
TI  - Autism spectrum disorder and psychopathy: shared cognitive underpinnings or
      double hit?
AB  - BACKGROUND: We measured psychopathic traits in boys with autism spectrum disorder
      (ASD) selected for difficult and aggressive behaviour. We asked (i) whether
      psychopathic tendencies can be measured in ASD independent of the severity of
      autistic behaviour; (ii) whether individuals with ASD with callous-unemotional
      (CU) traits differ in their cognitive profile from those without such traits; and
      (iii) how the cognitive data from this study compare with previous data of
      youngsters with psychopathic tendencies. METHOD: Twenty-eight ASD boys were rated
      on psychopathic tendencies, autistic traits and a range of cognitive measures
      assessing mentalizing ability, executive functions, emotion recognition and
      ability to make moral-conventional distinction. RESULTS: Our results indicate
      that psychopathic tendencies are not related to severity of ASD. In addition,
      such tendencies do not seem to be related to core autistic cognitive deficits,
      specifically in 'mind-reading' or executive function. Boys with co-occurring ASD
      and CU tendencies share some behaviours and aspects of cognitive profile with
      boys who have psychopathic tendencies alone. CONCLUSIONS: Callous/psychopathic
      acts in a small number of individuals with ASD probably reflect a 'double hit'
      involving an additional impairment of empathic response to distress cues, which
      is not part and parcel of ASD itself.

PMID- 17018170
TI  - Aggressive behaviour at first contact with services: findings from the AESOP
      First Episode Psychosis Study.
AB  - BACKGROUND: Aggressive behaviour is increased among those with schizophrenia but
      less is known about those with affective psychoses. Similarly, little is known
      about aggressive behaviour occurring at the onset of illness. METHOD: The main
      reasons for presentation to services were examined among those recruited to a UK
      based first episode psychosis study. The proportion of individuals presenting
      with aggressive behaviour was determined and these individuals were compared to
      those who were not aggressive on a range of variables including sociodemographic,
      clinical, criminal history, service contact, and symptom characteristics. Among
      the aggressive group, those who were physically violent were distinguished from
      those who were not violent but who were still perceived to present a risk of
      violence to others. RESULTS: Almost 40% (n=194) of the sample were aggressive at
      first contact with services; approximately half of these were physically violent
      (n=103). Younger age, African-Caribbean ethnicity and a history of previous
      violent offending were independently associated with aggression. Aggressive
      behaviour was associated with a diagnosis of mania and individual manic symptoms
      were also associated with aggression both for the whole sample and for those with
      schizophrenia. Factors differentiating violent from non-violent aggressive
      patients included male gender, lower social class and past violent offending.
      CONCLUSIONS: Aggressive behaviour is not an uncommon feature in those presenting
      with first episode psychosis. Sociodemographic and past offending factors are
      associated with aggression and further differentiate those presenting with more
      serious violence. A diagnosis of mania and the presence of manic symptoms are
      associated with aggression.

PMID- 17018171
TI  - Neural correlates of enhanced working-memory performance in dissociative
      disorder: a functional MRI study.
AB  - BACKGROUND: Memory functioning has been highlighted as a central issue in
      pathological dissociation. In non-pathological dissociation, evidence for
      enhanced working memory has been found, together with greater task-load related
      activity. So far, no imaging studies have investigated working memory in
      dissociative patients. METHOD: To assess working memory in dissociative patients
      functional magnetic resonance imaging was used during performance of a
      parametric, verbal working-memory task in patients with a dissociative disorder
      (n=16) and healthy controls (n=16). RESULTS: Imaging data showed that both groups
      activated brain regions typically involved in working memory, i.e. anterior,
      dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex.
      Dissociative patients showed more activation in these areas, particularly in the
      left anterior PFC, dorsolateral PFC and parietal cortex. In line with these
      findings, patients made fewer errors with increasing task load compared to
      controls, despite the fact that they felt more anxious and less concentrated
      during task performance. CONCLUSIONS: These results extend findings in non
      pathological high dissociative individuals, suggesting that trait dissociation is
      associated with enhanced working-memory capacities. This may distinguish
      dissociative patients from patients with post-traumatic stress disorder, who are
      generally characterized by impaired working memory.

PMID- 17018172
TI  - Female autonomy as a contributing factor to women's HIV-related knowledge and
      behaviour in three culturally contrasting States in India.
AB  - Factors contributing to India's vulnerability to the AIDS epidemic include
      pervasive poverty, low levels of education and high gender stratification. This
      study uses data collected in the 1998-99 National Family Health Survey-2 (NFHS-2)
      to investigate the relationship between aspects of women's autonomy and four
      measures of HIV-related knowledge and behaviour--awareness and knowledge of
      HIV/AIDS, condom awareness and condom use--in three culturally contrasting states
      in India: Kerala (n=2884), Karnataka (n=4357) and Uttar Pradesh (n=8981). The
      NFHS-2 is a nationally representative survey of India, with a sampling scheme
      that was designed such that each state sample can be generalized back to
      represent ever-married women aged 15-49 living in the state. Kerala scores
      highest in the four health outcome measures, followed by Karnataka and then Uttar
      Pradesh, but condom use is lowest in Karnataka. Kerala also leads in the four
      dimensions of autonomy examined and in socio-demographic status, followed again
      by Karnataka and Uttar Pradesh. Despite these observed differences, in all three
      states, women with greater autonomy as measured by this study were more likely to
      be knowledgeable about AIDS and condoms and to use condoms, after controlling for
      socio-demographic factors. These results concur with other studies focusing on
      women's autonomy and health outcomes around the world, and point to the
      importance of incorporating a gender-based approach to AIDS prevention programmes
      in India.

PMID- 17018174
TI  - CT recognition of traumatic pneumomyelogram.

PMID- 17018173
TI  - Influence of height on attained level of education in males at 19 years of age.
AB  - In this study it is hypothesized that taller individuals are more likely to move
      up the scale of educational attainment compared with shorter individuals from the
      same social background. Three national cohorts of 19-year-old males were
      considered: 29,464 born in 1967 and surveyed in 1986, 31,062 born in 1976 and
      surveyed in 1995, and 30,851 born in 1982 and surveyed in 2001. Four social
      variables were used to describe the social background of each conscript in the
      three surveys: degree of urbanization, family size, and parental and maternal
      educational status. The educational status of each conscript was classified into
      two groups: (1) those who were secondary school students or graduates, or who had
      entered college, and (2) those who had completed their education at the primary
      school level or who had gone to a basic trade school. Multiple binomial logistic
      regressions were used to estimate the relative risk of achieving higher
      educational status by 19-year-old males relative to height and the four social
      factors. Consistently across the three cohorts the odd ratios (ORs) indicate that
      height exerts an independent and significant effect on the attained level of
      education at the age of 19 years in males (1986: OR=1.24, p<0.001; 1995: OR=1.24,
      p <0.001; 2001: OR=1.20, p<0.001). Two possible, not mutually exclusive,
      selective mechanisms are postulated and discussed: 'passive' and 'active' action.

PMID- 17018175
TI  - Use of the ProSeal LMA in the ICU to facilitate weaning from controlled
      ventilation in patients with severe two episodic bronchospasm.

PMID- 17018176
TI  - Prolonged use of the ProSeal laryngeal mask in ICU: a case report.

PMID- 17018177
TI  - A case of Churg-Strauss syndrome undergoing radical mastectomy under general
      anaesthesia and thoracic epidural analgesia.

PMID- 17018178
TI  - Anaesthetic management of an extremely obese woman undergoing open gastric
      bypass.

PMID- 17018179
TI  - Accidental switching off of an anaesthetic machine.

PMID- 17018180
TI  - Clinicians' attitudes to spirituality in old age psychiatry.
AB  - BACKGROUND: The aim of this survey is to investigate professional attitudes to
      the presence and value of spiritual care from Old Age Psychiatrists. METHOD: All
      registered members of the Faculty of the Psychiatry of Old Age in the United
      Kingdom were asked to complete a 21-question semi-structured questionnaire. The
      first mail shot took place in 2002 and the second mail shot to non-respondents in
      2003. Quantitative and qualitative analyses were carried out on the answers
      received. RESULTS: The response rate was 46%. The majority of respondents (92%)
      recognize the importance of spiritual dimensions of care for older people with
      mental health needs and about a quarter of respondents appear to consider
      referring patients to the chaplaincy service. In contrast, integration of
      spiritual advisors within the assessment and management of individual cases is
      rare. CONCLUSIONS: Opinions vary as to whether provision of spiritual care should
      become widely available to older people with mental health needs who are admitted
      to hospital. Old age psychiatrists recognize that awareness of spiritual
      dimensions may be important for their patients. They seem less clear about the
      role of spiritual advisors and how NHS multidisciplinary clinical teams and
      spiritual and pastoral care services can be best integrated. Much work needs to
      be done on developing effective training and operational policies in this area.

PMID- 17018181
TI  - Stress-related reduction in personal mastery is associated with reduced immune
      cell beta2-adrenergic receptor sensitivity.
AB  - BACKGROUND: A growing body of literature suggests that caregiving burden is
      associated with impaired immune system functioning, which may contribute to
      elevated morbidity and mortality risk among dementia caregivers. However,
      potential mechanisms linking these relationships are not well understood. The
      purpose of this study was to investigate whether stress-related experience of
      depressive symptoms and reductions in personal mastery were related to
      alterations in ss2-adrenergic receptor sensitivity. METHODS: Spousal Alzheimer's
      caregivers (N = 106) completed measures assessing the extent to which they felt
      overloaded by their caregiving responsibilities, experienced depressive symptoms,
      and believed their life circumstances were under their control. We hypothesized
      that caregivers reporting elevated stress would report increased depressive
      symptoms and reduced mastery, which in turn would be associated with reduced ss2-
      adrenergic receptor sensitivity on peripheral blood mononuclear cells (PBMC), as
      assessed by in vitro isoproterenol stimulation. RESULTS: Regression analyses
      indicated that overload was negatively associated with mastery (beta = -0.36, p =
      0.001) and receptor sensitivity (beta = -0.24, p = 0.030), whereas mastery was
      positively associated with receptor sensitivity (beta = 0.29, p = 0.005).
      Finally, the relationship between overload and receptor sensitivity diminished
      upon simultaneous entry of mastery. Sobel's test confirmed that mastery
      significantly mediated some of the relationship between overload and receptor
      sensitivity (z = -2.02, p = 0.044). CONCLUSIONS: These results suggest that a
      reduced sense of mastery may help explain the association between caregiving
      burden and reduced immune cell ss2-receptor sensitivity.

PMID- 17018182
TI  - Children and adults recall the names of highly familiar faces faster than
      semantic information.
AB  - Adults find it harder to remember the names of familiar people than other
      biographical information such as occupation or nationality. It has been suggested
      that the opposite effect occurs in children (Scanlan & Johnston, 1997). We failed
      to replicate the effects found by Scanlan and Johnston and instead found that
      children were slower to match a name than an occupation to a famous face
      (Experiment 1). In Experiments 2 and 3, however, we show a temporal advantage for
      names in both adults and children when highly familiar faces are used. This is
      the case for famous and personally known faces. These results show that the speed
      of name retrieval is influenced by familiarity in the same way in both children
      and adults and indicate that children do not represent knowledge for familiar
      people differently from adults. The implications of these results for current
      models of name retrieval difficulties are discussed.

PMID- 17018183
TI  - Digit ratio and faculty membership: implications for the relationship between
      prenatal testosterone and academia.
AB  - Digit ratio (length of index finger divided by length of ring finger) is an index
      of exposure to prenatal testosterone. Prenatal testosterone slows the growth rate
      of the left side of the brain while enhancing growth of the right side. Right
      hemisphere processing is associated with better visual-spatial and mathematical
      abilities, as is digit ratio. Thus, traditional sex differences in visual-spatial
      and mathematical abilities can be attributed to differences in exposure to
      prenatal testosterone, indexed by a sex dimorphic pattern in digit ratio
      (female=1.00, male=0.98 for UK samples). Additionally, the digit ratio is a
      marker for within-sex variance in visual-spatial ability. This study examines the
      digit ratio of an academic sample. No sex differences are found and there is a
      significant difference between the Science Faculty and Social Science Faculty.
      Social Scientists of both sexes have a ratio consistent with the male norm (0.98)
      whilst Scientists have a digit ratio consistent with the female norm (1.00).
      These results are discussed in terms of the lower normal range of male
      testosterone being associated with highest visual spatial abilities.
      Relationships with fertility and Dyslexia are also identified.

PMID- 17018184
TI  - Immediate disambiguation of lexically ambiguous words during reading: evidence
      from eye movements.
AB  - Sentences containing lexically ambiguous words were read as readers' eye
      movements were monitored. On half of the trials, the dominant meaning of the
      ambiguous word was instantiated, while in the other half, the subordinate meaning
      was instantiated. Furthermore, on half of the trials, an adjective or modifier
      immediately preceded the target noun (kitchen table, statistical table), which
      was consistent with either the dominant or subordinate meaning. The results of
      the experiment demonstrate that readers are able to immediately utilize the
      modifier to select the appropriate meaning of the ambiguous word.

PMID- 17018185
TI  - 'I was like a wild wild person': understanding feelings of anger using
      interpretative phenomenological analysis.
AB  - This paper is concerned with illuminating how emotion (anger) and emotion-related
      phenomena such as feelings, thoughts and expressions appear to the individual
      person. In particular, it focuses on the role of feelings in emotion experience.
      It does this through the qualitative analysis of interview material from a single
      person case study using interpretative phenomenological analysis. The paper
      examines how the participant feels and experiences anger, the defining
      characteristics of anger episodes, and how the typical pattern of these episodes
      is disrupted by life-changes. The findings are examined in light of
      phenomenological ideas and the utility of these ideas for psychology's
      understanding of emotion argued for.

PMID- 17018186
TI  - Religious coping research and contemporary personality theory: an exploration of
      Endler's (1997) integrative personality theory.
AB  - Notable weaknesses in the literature on religion and mental health include
      theoretical inconsistencies and lack of integration with contemporary personality
      theory. The current study explored a potential solution to these theoretical
      limitations. A modified form of Endler's (1997) interactive model of personality
      was applied to the prediction of religious coping and tested using structural
      equation modelling. As predicted by the model, personality dispositions predicted
      coping directly, as well as indirectly through perception of the situation and
      situational anxiety. These patterns were, as expected, found to interact with the
      type of situation. Results indicated that having a positive disposition appears
      to buffer one's negative perceptions of situations over which one has little
      control. Participants tended to use more religious coping in low-control
      situations; in high-control situations, participants tended not to use negative
      religious coping techniques such as pleading for miracles.

PMID- 17018187
TI  - Cross-sectional and longitudinal relations between mother-child talk about
      conflict and children's social understanding.
AB  - We examined the relations between the ways 48 mothers and their 3- to 5-year-olds
      talked about a conflict depicted in a picture book and their children's current
      and subsequent level of social understanding. We distinguished explanatory talk,
      which directed attention to the actions that generated the conflict, from non
      explanatory talk, which discussed the conflict in terms of, for example, making
      up or saying sorry. Controlling for child age and overall talk by mother,
      explanatory talk was positively associated with contemporaneous social
      understanding. Social understanding at time one was also positively associated
      with social understanding 30 months later. These data suggest that dialogue about
      conflict may be helpful for 3- to 5-year old children's understanding of the
      mental world, to the extent that it facilitates their understanding of particular
      social situations.

PMID- 17018188
TI  - Do people with autistic spectrum disorder show normal selection for attention?
      Evidence from change blindness.
AB  - People in the general population are typically very poor at detecting changes in
      pictures of complex scenes. The degree of this 'change blindness', however,
      varies with the content of the scene: when an object is semantically important or
      contextually inappropriate, people may be more effective at detecting changes.
      Two experiments investigated change blindness in people with autism, who are
      known from previous research to be efficient in detecting features yet poor at
      processing stimuli for meaning and context. The first experiment measured the
      effect of semantic information while the second investigated the role of context
      in directing attention. In each task, participants detected the dissimilarity
      between pairs of images. Both groups showed a main effect of image type in both
      experimental tasks, showing that their attention was directed to semantically
      meaningful and contextually inappropriate items. However, the autistic group also
      showed a greater difficulty detecting changes to semantically marginal items in
      the first experiment. Conclusions point to a normal selection of items for
      attention in people with autism spectrum disorders, although this may be combined
      with difficulty switching or disengaging attention.

PMID- 17018189
TI  - Aesthetic activities and aesthetic attitudes: influences of education, background
      and personality on interest and involvement in the arts.
AB  - There have been few studies of why some people are frequently involved in
      aesthetic activities such as going to the theatre, reading or playing musical
      instruments, whereas others are less involved. This study assesses the broad
      roles of education, personality and demographic factors such as social class, age
      and sex. More aesthetic activity was associated with music and art education,
      whereas science education had a substantial negative relationship with aesthetic
      activity, both directly and also indirectly via reduced art education. More
      aesthetic activity was particularly related to higher scores on the personality
      factor of openness, and also to lower scores on agreeableness and
      conscientiousness. Higher parental social class was also associated with more
      aesthetic activity, as also was lower age. Sex had no relationship to aesthetic
      activity, as neither did masculinity-femininity. Positive aesthetic attitudes
      were also related moderately to aesthetic activity, but were particularly
      strongly related to openness to experience, and somewhat less to extraversion.
      Class, age and sex had no direct relationship to aesthetic attitudes.

PMID- 17018190
TI  - An exercise in fatuity: research governance and the emasculation of HSR.

PMID- 17018191
TI  - How might the way you look influence how well you are looked after?

PMID- 17018192
TI  - Does continuity of care with a family physician reduce hospitalizations among
      older adults?
AB  - OBJECTIVE: To examine the relation between continuity of primary care and
      hospitalizations. METHODS: Survey data from a representative sample of older
      adults aged 67 or over living in the province of Manitoba (n = 1863) were linked
      to administrative data, which provide complete records of physician visits and
      hospitalizations. A visit-based measure of continuity of care was derived using a
      majority-of-care definition, whereby individuals who made 75% of all their visits
      to family physicians (FPs) to the same FP were classified as having high
      continuity of care, and those with less than 75% of their visits to the same FP
      as having low continuity of care. Whether individuals were hospitalized (for
      either ambulatory care-sensitive conditions or all conditions) was also
      determined from administrative records. RESULTS: High continuity of care was
      associated with reduced odds of ambulatory care-sensitive hospitalizations
      (adjusted odds ratio = 0.67, confidence interval 0.51-0.90) controlling for
      demographic and self-reported, health-related measures. It was not related to
      hospitalizations for all conditions, however. CONCLUSIONS: The study highlights
      the importance of continuity of primary care in reducing potentially avoidable
      hospitalizations.

PMID- 17018193
TI  - Gathering data for health care regulation: learning from experience in England
      and Wales.
AB  - OBJECTIVES: Between 2000 and 2004, the Commission for Health Improvement (CHI)
      undertook a comprehensive programme of reviews of progress with clinical
      governance in National Health Service trusts (provider organizations) in England
      and Wales. An internal retrospective evaluation of the main instruments and
      processes used to gather evidence for these reviews was undertaken to identify
      lessons for the future development of health care regulation methods. METHODS: A
      multimethod retrospective study involving review of data-gathering tools
      previously undertaken by CHI, an intranet-based survey and confidential
      interviews with CHI staff. The study reviewed 11 instruments and processes used
      to gather information about trusts from routine data-sets, internal documents,
      staff, patients and the public, local statutory bodies, and community and
      voluntary stake-holders. Analysis focused on inputs required (skills and
      resources required to use the approaches effectively and challenges associated
      with their use) and value obtained (relevance and quality of the information
      obtained and its contribution to clinical governance review conclusions).
      RESULTS/CONCLUSIONS: Most of the instruments and processes evaluated had the
      potential to elicit worthwhile information for clinical governance reviews, but
      in practice their value varied considerably. A range of factors, within and
      beyond CHI, was found to affect the quality of the data obtained. Based on this
      learning, lessons are identified whose implementation would help optimize the
      quality of data gathering for health care regulation.

PMID- 17018194
TI  - Exploring the determinants of NHS performance ratings: lessons for performance
      assessment systems.
AB  - OBJECTIVES: A basic tenet of effective performance management is that decision
      makers should be held responsible only for aspects of performance over which they
      have control. We examine the degree to which variations in the performance of
      health care organizations are explained by a range of factors that are subject to
      differing degrees of managerial control. METHODS: We use multiple regression
      methods and data on 304 National Health Service (NHS) Primary Care Trusts (PCTs)
      in England for 2002/03 to analyse the relationship between their performance, as
      measured by 'star ratings' and nine key performance targets, and a large number
      of explanatory variables. We classify the explanatory variables into five groups
      along a spectrum from 'no managerial control' to 'total managerial control'. We
      also analyse the relationship between PCTs that are service purchasers and their
      main providers to assess the degree to which their performance is linked.
      RESULTS: For all of the key performance targets, most of the variation in
      performance is unexplained, although variables in groups 1, 2 and 3 (less
      managerial control) explain the largest proportion of variation. We find some
      evidence that socioeconomic and geographic factors have an impact on performance.
      We also find a positive relationship between the performances of purchaser and
      provider organizations. CONCLUSIONS: The star ratings did not allow for the
      different environmental circumstances within which PCTs operate and which affect
      their performance. Policy-makers should exercise caution in using such
      performance indicators to regulate health care organizations.

PMID- 17018195
TI  - A comparison of formal consensus methods used for developing clinical guidelines.
AB  - OBJECTIVES: To compare two consensus development methods commonly used for
      developing clinical guidelines in terms of the judgments produced, closeness of
      consensus, amount of change between rounds, concordance with research evidence
      and reliability. METHODS: In all, 213 general practitioners and mental health
      professionals from England participated in four Delphi and four nominal groups.
      They rated the appropriateness of four treatments (cognitive behavioural therapy
      [CBT], behavioural therapy [BT], brief psychodynamic interpersonal therapy [BPIT]
      and antidepressants) for three conditions. First, participants rated the
      appropriateness of interventions independently, using a postal questionnaire. For
      nominal groups, the ratings were fed back and discussed at a meeting, and then
      group members privately completed the questionnaire again. For Delphi groups,
      there was feedback but no discussion, and the entire process was conducted by
      postal questionnaire. RESULTS: The effect of consensus method on final ratings
      varied with therapeutic intervention, with nominal groups rating CBT and
      antidepressants more favourably than Delphi groups. Consensus was closer in the
      nominal than in the Delphi groups in both rounds. There was no overall difference
      between groups in their concordance with research evidence (odds ratio 1.13, 95%
      confidence interval 0.79-1.61). In this study, the Delphi method was more
      reliable (kappa coefficients 0.88 and 0.89 compared with 0.41 and 0.65 for
      nominal groups). CONCLUSIONS: The advantages of nominal groups (more consensus;
      greater understanding of reasons for disagreement) could be combined with the
      greater reliability of the Delphi approach by developing a hybrid method.

PMID- 17018196
TI  - Is self-care a cost-effective use of resources? Evidence from a randomized trial
      in inflammatory bowel disease.
AB  - OBJECTIVES: To determine if a whole-system approach to self-management in
      inflammatory bowel disease (IBD), using a guidebook developed with patients and
      physicians trained in patient-centred care, leads to cost-effective use of health
      system resources. METHODS: Cost-effectiveness analysis over a one-year time
      horizon comparing the whole systems self-management approach to treatment with
      usual treatment. Nineteen hospitals in the northwest England were randomized to
      the intervention or to be controls; 651 patients (285 at intervention sites and
      366 at control sites) with established IBD were included. The economic evaluation
      related differential health service costs, from a UK NHS perspective, to
      differences in quality-adjusted life years (QALYs) based on patients' responses
      to the EQ-5D. RESULTS: The intervention was associated with a mean reduction in
      costs of 148 pounds sterling per patient and a small mean reduction in QALYs of
      0.00022 per patient compared with the control group. This resulted in an
      incremental cost per QALY gained of 676,417 pounds sterling for treatment as
      usual and a probability of around 63% that the whole-system approach to self
      management is cost-effective, assuming a willingness to pay up to 30,000 pounds
      sterling for an additional QALY. CONCLUSIONS: Although there is uncertainty
      associated with these estimates, more widespread use of this method in chronic
      disease management seems likely to reduce health care costs without evidence of
      adverse effect on patient outcomes.

PMID- 17018197
TI  - Might how you look influence how well you are looked after? A study which
      demonstrates that GPs perceive socio-economic gradients in attractiveness.
AB  - OBJECTIVE: To test the hypothesis that more disadvantaged patients are perceived
      by general practitioners (GPs) as being less attractive than their more affluent
      peers. DESIGN: Three hundred and twenty five consecutive ambulant patients
      attending 15 GPs' surgeries in Northern Ireland, UK, had three digital
      photographs taken; two of their face (smiling and non-smiling) and one of their
      face and upper trunk. Photographs were assessed by 30 GPs from practices other
      than those used to select the patients. Patients were subdivided into 'more
      affluent', 'average' and 'more deprived' groups based on their household tenure,
      level of educational attainment and car availability. The age and sex of the GP
      assessors was recorded along with the average deprivation score for their own
      practice population. The relationship between patient, GP and practice
      characteristics was explored using multilevel modelling to take account of the
      hierarchical nature of the dataset. The main outcome measure was the perceived
      attractiveness score of the patient as rated by the GP. RESULTS: Of those
      invited, 301 (92%) participated in the study. The mean age of patients was 49.6
      (standard deviation 6.1) years and 59% were female. GPs rated younger patients
      more attractive than older patients; each additional 10 years reduced the
      attractiveness scores by an average of 2.7 points (95% confidence intervals 1.4
      3.9, P < 0.001). Patients from higher socio-economic backgrounds were assessed as
      more attractive than their less affluent peers, the mean difference being 7.8
      points (5.8-9.9, P < 0.001). The difference in attractiveness scores between
      affluent and deprived patients was greatest when the GP assessor came from a
      practice serving predominantly deprived patients. CONCLUSION: The perceived
      difference in the average attractiveness scores between affluent and deprived
      patients is large and, though this study does not prove it, there is sufficient
      circumstantial evidence to indicate that it might play a significant role in
      modifying the medical encounter.

PMID- 17018198
TI  - Better the devil you know than the doctor you don't: is advertising drugs to
      doctors more harmful than advertising to patients?
AB  - Most countries ban the advertising of prescription medication directly to
      consumers, yet allow drug companies to promote drugs to doctors intensively. Such
      a differential treatment of promotion cannot be justified on economic grounds,
      but is a result of paternalism in health care regulation, which portrays patients
      as gullible and doctors as perfect agents. Instead, there should be a complete
      deregulation of direct-to-consumer (DTC) advertising and doctors ought to be
      required to reveal their relationships with drug companies. This is particularly
      apt, given the calls for similar transparency rules to address the potential
      conflict of interest between drug companies and researchers.

PMID- 17018199
TI  - A systematic review of evidence about extended roles for allied health
      professionals.
AB  - OBJECTIVE: Extending the role of allied health professionals has been promoted as
      a key component of developing a flexible health workforce. This review aimed to
      synthesize the evidence about the impact of these roles. METHODS: A systematic
      review of extended scope of practice in five groups: paramedics,
      physiotherapists, occupational therapists, radiographers, and speech and language
      therapists. The nature and effect of these roles on patients, health
      professionals and health services were examined. An inclusive approach to
      searching was used to maximize potential sources of interest including multiple
      databases, 'grey' literature and subject area experts. An expanded Cochrane
      Collaboration method was used in view of the anticipated lack of randomized
      controlled trials and heterogeneity of designs. Papers were only excluded after
      the search stage for lack of relevance. RESULTS: A total of 355 papers was
      identified as meeting relevance criteria and 21 studies progressed to full review
      and data extraction. The primary reason for exclusion from data extraction was
      that the study included neither qualitative nor quantitative data or because
      methodological flaws compromised data quality. It was not possible to evaluate
      any pooled effects as patient health outcomes were rarely considered.
      CONCLUSIONS: A range of extended practice roles for allied health professionals
      have been promoted and are being undertaken, but their health outcomes have
      rarely been evaluated. There is also little evidence as to how best to introduce
      such roles, or how best to educate, support and mentor these practitioners.

PMID- 17018200
TI  - What is 'continuity of care'?
AB  - Continuity of care is concerned with the quality of care over time. There are two
      important perspectives on this. Traditionally, continuity of care is idealized in
      the patient's experience of a 'continuous caring relationship' with an identified
      health care professional. For providers in vertically integrated systems of care,
      the contrasting ideal is the delivery of a 'seamless service' through
      integration, coordination and the sharing of information between different
      providers. As patients' health care needs can now only rarely be met by a single
      professional, multidimensional models of continuity have had to be developed to
      accommodate the possibility of achieving both ideals simultaneously. Continuity
      of care may, therefore, be viewed from the perspective of either patient or
      provider. Continuity in the experience of care relates conceptually to patients'
      satisfaction with both the interpersonal aspects of care and the coordination of
      that care. Experienced continuity may be valued in its own right. In contrast,
      continuity in the delivery of care cannot be evaluated solely through patients'
      experiences, and is related to important aspects of services such as 'case
      management' and 'multidisciplinary team working'. From a provider perspective,
      the focus is on new models of service delivery and improved patient outcomes. A
      full consideration of continuity of care should therefore cover both of these
      distinct perspectives, exploring how these come together to enhance the patient
      centredness of care.

PMID- 17018202
TI  - A parallel private system would reduce waiting times in the public system.

PMID- 17018203
TI  - What are the effects of health care reforms on gender equity, particularly in
      health?

PMID- 17018205
TI  - Guidelines for health and welfare monitoring of fish used in research.
AB  - The aim of this paper is to provide background material necessary for the
      development of international guidelines for the health and welfare monitoring of
      fish used in research. It provides an overview of present guidelines and
      discusses why more detailed and species-specific guidelines are needed. A major
      issue within fish research is to document the situation today and point out areas
      where improvements are needed.

PMID- 17018206
TI  - Refined anaesthesia for implantation of engineered experimental aortic valves in
      the pulmonary artery using a right heart bypass in sheep.
AB  - The feasibility of an anaesthetic protocol developed for surgery during right
      heart bypass in sheep is reported. Seven female Suffolk sheep, weighing 25-35 kg,
      were selected for the study. Premedication consisted of midazolam and methadone
      (both 0.1 mg kg(-1) intravenously). Anaesthesia was induced with propofol (2-4 mg
      kg(-1)) and maintained with isoflurane in oxygen and continuous rate infusions of
      propofol (5-7 mg kg(-1 )h(-1)) and fentanyl (5 microg kg(-1) bolus, 5 microg kg(
      1) h(-1)). Cisatracurium (0.2 mg kg(-1)) provided muscle relaxation. A standard
      roller pump was used for the extracorporeal circulation. Drugs administered to
      maintain blood pressure and heart rate within acceptable levels included
      phenylephrine (3-4 microg kg(-1)), ephedrine (0.1-0.2 mg kg(-1)), nitroglycerine
      (50-150 microg kg(-1) h(-1)) and metoprolol succinate (30-80 microg kg(-1)).
      Electrolytes were infused as needed. Postoperative analgesia was provided by an
      intercostal block (15 mL 0.5% bupivacaine + epinephrine), carprofen (4 mg kg(-1))
      and an opioid (methadone 0.1 mg kg(-1) or buprenorphine 0.01 mg kg(-1)). One
      sheep became hypoxic during the bypass (PaO(2) 47.7 mmHg). Irregularities of the
      electrocardiogram were observed during manipulation of the heart in all animals.
      During the initial phase of the bypass, blood pressure decreased in all sheep,
      accompanied by dilatation of the heart and large intrathoracic veins in five
      sheep. With appropriate treatment, blood pressure was restored and easily
      maintained until the end of the bypass. Weaning from the bypass, using an
      infusion of nitrates, was smooth. One sheep required a blood transfusion because
      of severe blood loss and another sheep died postoperatively from respiratory
      complications. Minor irregularities of the electrocardiogram observed during
      manipulation of the heart were not life threatening and required no treatment.
      Decreases in blood pressure at the beginning of the bypass can be expected and
      require treatment. Nitrates are useful in avoiding volume overload during
      weaning. The anaesthetic protocol is acceptable for surgery under right heart
      bypass in sheep.

PMID- 17018207
TI  - Long-term effects of cage-cleaning frequency and bedding type on laboratory rat
      health, welfare, and handleability: a cross-laboratory study.
AB  - Cage-cleaning is necessary for a hygienic environment, but since rats communicate
      using scent, they might suffer if their cages are cleaned too frequently. Male
      rats (Sprague-Dawley and Wistar) were kept for five months across four animal
      units. Their cages were cleaned twice-weekly, weekly, or every two weeks, and
      contained either aspen woodchips or absorbent paper bedding. Aggression, injuries
      and general health, weight gain, chromodacryorrhoea (a stress-related Harderian
      gland secretion), handleability, and lung pathology were monitored, as was in
      cage ammonia. Cleaning frequency had no clear impact on rat welfare, although
      frequent cleaning decreased ammonia concentrations and handleability, and non
      aggressive skirmishing was highest in weekly cleaned rats. Surprisingly, bedding
      type did not affect ammonia, but all ammonia readings were unexpectedly low.
      However, rats kept on aspen had greater sneezing rates and lung pathology than
      those on paper bedding, but also had higher body weights. The results raise
      concerns about aspen bedding, which is relatively inert compared with other wood
      beddings, but nevertheless more harmful than paper. Animal unit significantly
      affected eight of the 11 variables tested, having interactive effects on five of
      them. The study also demonstrates the interactive effects of different animal
      units, casting doubt on the feasibility of standardization. We explored multiple
      variables of interest, so all findings require confirmation through further work.
      Nevertheless, cage-cleaning rates seem to affect socially housed male rats
      little, while bedding type has important effects on rat health.

PMID- 17018208
TI  - Effects of light or dark phase testing on behavioural and cognitive performance
      in DBA mice.
AB  - Behavioural experiments in mice are often carried out during the resting phase of
      these nocturnal animals. Ignoring the fact that mice are more active during the
      dark period, results from resting-phase testing has also been used to
      characterize these animals. Since the influence of the light/dark cycle on
      testing is likely to be a relevant factor for the analysis of behavioural
      results, the aim of this study was to evaluate the effects of the relative time
      of the day as well as light conditions during testing on behavioural and
      cognitive performance in inbred mice. Naive DBA/2N (DBA) mice were tested in the
      modified hole board (mHB) either during the dark phase under red light or during
      the light phase under white light. Different behavioural dimensions and cognitive
      functions were evaluated in parallel. Depending on the testing conditions, the
      results showed significant differences in behavioural activity, with DBA mice
      being less inhibited during dark phase. The same experimental group made fewer
      memory errors in a visuo-spatial task and showed a faster habituation compared
      with the group tested during the dark phase. From the results we conclude that
      testing during the light phase induces a pronounced behavioural inhibition as
      well as a cognitive disruption in DBA mice, which should be taken into account
      when cognitively testing these animals.

PMID- 17018209
TI  - Effect of restraint and injection methods on heart rate and body temperature in
      mice.
AB  - Routine procedures in the laboratory, inducing acute stress, will have an impact
      on the animals and might thereby influence scientific results. In an attempt to
      gain more insight into quantifying this acute stress by means of the parameters
      heart rate (HR) and body temperature (BT), we subjected mice to different
      restraint and injection methods. We first compared the treatment response of HR
      and BT, measured by means of radiotelemetry, with the treatment response of
      plasma corticosterone (pCORT), a common and well-validated parameter for
      measuring acute stress responses. It was found that HR, and to a lesser extent
      also BT, parallels pCORT values after subjecting the animals to different methods
      of restraint. Secondly, the acute stress response caused by different injection
      methods was evaluated. Again, HR was found to be a more sensitive parameter than
      BT. We found that, in case of sham injections, the acute stress response after an
      intraperitoneal (i.p.) injection was more pronounced than after intramuscular
      (i.m.) or subcutaneous (s.c.) injections, but this difference was found to be
      inconsistent when saline was used as injection fluid. In a third experiment we
      investigated if the level of experience of the animal technician influenced the
      stress response after s.c. injections, but no differences were found. Overall,
      the results have indicated that HR might be considered as a useful parameter for
      measuring acute stress responses to routine procedures, but the value of BT seems
      to be of limited value in this respect.

PMID- 17018210
TI  - Behaviour of laboratory mice in different housing conditions when allowed to self
      administer an anxiolytic.
AB  - Standard cages prevent mice from performing several natural behaviours for which
      they are motivated. As a consequence, abnormal behaviours sometimes develop and
      mice often spend long periods inactive. To improve welfare, cages are sometimes
      furnished with items such as nesting material, shelters and running wheels. We
      have previously reported that when allowed to self-administer an anxiolytic, mice
      in furnished cages consume less anxiolytic than mice in standard cages. This
      paper presents the results of behaviour studies of the mice in the same
      experiment. Female C57BL/6J mice (3 per cage) were housed in Standard (n = 10),
      Unpredictable (n = 10) or Furnished (n = 6) cages. Unpredictable cages were
      identical to Standard cages, but were exposed to unpredictable events two to
      three times a week. Furnished cages were double the size of Standard cages and
      contained nesting material, nest box, tubes, chew blocks and a running wheel.
      During three consecutive periods, mice had access to only water (control), water
      or an anxiolytic solution on a daily alternating schedule (forced consumption),
      and finally, both water and anxiolytic (self-administration). Behaviour was
      analysed from video recordings taken during the dark phase. The housing type
      affected behaviour both under the control and the self-administration conditions.
      Overall, mice in Furnished cages spent less time resting and performing bar
      related behaviours and more time on exploratory/locomotory behaviours. Mice in
      Furnished cages also performed less bar-circling stereotypies than mice in
      Standard cages. The Unpredictable treatment did not significantly affect
      behaviour compared to mice in the Standard conditions. There was an overall
      effect of anxiolytic availability on rest-related behaviours and on exploration
      locomotion behaviours, in that mice rested more and spent less time on
      exploration and locomotion when they were able to self-administer the anxiolytic.

PMID- 17018211
TI  - Role of cage material, working style and hearing sensitivity in perception of
      animal care noise.
AB  - During daily care, laboratory animals are exposed to a variety of sounds which
      may have effects on welfare and also cause physiological and behavioural changes.
      So far, almost no attention has been paid to individual sounds or the sound level
      caused by animal care or the sound level inside the animal cage. In this study,
      sounds from selected rat care procedures were recorded: pulling cage out of the
      rack, placing it onto a table and replacing the cage back into the rack; with
      measurements made inside the rat cage and in the adjacent cage. Diet was poured
      into the food hopper and sounds were recorded inside the cage and also the
      adjacent cage. The work was repeated in a calm and also in a hurried style, using
      stainless steel and polycarbonate cages. Finally, the sounds produced by running
      tap water were recorded. Differences between rat and human hearing were compared
      using novel species-specific sound level weightings: R-weighting for rats dB(R)
      and H-weighting for human dB(H). Hurried work with steel caused sound exposure
      levels exceeding 90 dB(R) when the cages were placed into the rack and about 80
      dB(R) when pulling them out of the rack or placing onto a table. With
      polycarbonate, the levels were 10-15 dB(R) lower. Unhurried calm working produced
      lower sound exposure levels than hurried working in many procedures. When the
      procedures were repeated with measurements in the adjacent cage, the sound
      exposure levels were lower, but the results were similar. Pouring food pellets
      into a hopper above the rat's head caused 15 dB(R) higher sound exposure levels
      than pouring food to an adjacent cage. In general, humans hear these sounds about
      10-15 dB louder than rats. In conclusion, cage material, working style and
      hearing sensitivity all have an impact on the sound exposure level in the rodent
      cage. With correct working methods, high sound levels can be efficiently avoided
      in most cases.

PMID- 17018212
TI  - Preference for bedding material in Syrian hamsters.
AB  - This study aimed to determine whether Syrian (golden) hamsters, Mesocricetus
      auratus, prefer certain bedding materials and whether bedding material can affect
      paw condition, body weight gain and wheel-running activity. In a first
      experiment, 26 male hamsters had access to two connected cages, each cage
      containing a different bedding material (either pine shavings, aspen shavings,
      corn cob or wood pellets). In a second experiment, 14 male hamsters had access to
      four connected cages that contained the different bedding materials and also a
      piece of paper towel to serve as nest material. In a third experiment, 30 male
      hamsters were each placed in a single cage, 10 of them with pine shavings, 10
      with aspen shavings and 10 with corn cob, and they were monitored for 50 days.
      Significant preferences in the first experiment were: pine shavings over aspen
      shavings, corn cob over wood pellets, pine shavings over corn cob and aspen
      shavings over wood pellets (aspen shavings versus corn cob was not tested).
      However, there was no significant preference expressed in the second experiment,
      suggesting that the general preference for shavings in the first experiment was
      based on bedding material suitability as a nesting material. No significant
      effect of bedding material on paw condition, body weight gain and wheel-running
      activity was detected. None of the four bedding materials tested in this study
      can be judged to be inappropriate in the short term if nesting material is added
      to the cage and if the litter is changed regularly.

PMID- 17018213
TI  - Effects of an individually ventilated cage system on the airway integrity of rats
      (Rattus norvegicus) in a laboratory in Brazil.
AB  - The ventilation method used in the management of laboratory rats is important in
      maintaining their health. Rats kept under general diluting ventilation (GDV) are
      exposed to high levels of pollutants present in the environment (dust, airborne
      bacteria, etc.) or those pollutants produced by animal metabolism and excretion
      inside the boxes (e.g. ammonia and carbon dioxide). These pollutants may
      contribute to respiratory pathologies. An alternative experimental ventilation
      system for laboratory animal housing using intracage ventilation technology
      (individually ventilated cage system, IVC) was developed. In this system, ammonia
      levels decreased and rats exhibited better reproductive performance and a lower
      incidence of pneumonia than rats maintained under GDV. Using two different levels
      of air speed (0.03-0.26 m/s: IVC(1); 0.27-0.80 m/s: IVC(2)), the effects of IVC
      were compared with GDV (control) in Wistar rats in terms of respiratory mucus
      properties, on the nasal epithelium (as measured by quantitative morphometry) and
      on the lungs (as determined by the cellular composition obtained by
      bronchoalveolar lavage). Mucus of the respiratory system was evaluated using the
      following techniques: rheology (viscoelasticity) by microrheometer, in vitro
      mucociliary transportability (frog palate) and contact angle (an indicator of
      adhesivity). Also, membrane transepithelial potential difference was measured as
      a biomarker of airway integrity. After bedding was changed, ammonia
      concentrations inside the cages on day 3 were significantly higher for GDV than
      for IVC(1) and IVC(2). The potential-difference values for IVC(1), IVC(2) and GDV
      in the epiglottis and in the trachea also showed differences. Although some
      significant differences were observed across the three groups in counts of some
      cell types, the intragroup results were highly variable among individuals and
      inconsistent between sexes. No significant differences in the other parameters
      were found across groups. These results establish that rats maintained under GDV
      in relatively unregulated conditions are exposed to factors that can lead to
      deleterious effects on the ciliated epithelium of the airways, and that these
      effects can be prevented by the use of IVC.

PMID- 17018214
TI  - Islet-like cell clusters: viability, cell types, and subretinal transplantation
      in pancreatectomized cats.
AB  - We investigated a method for isolating sufficient feline islets of Langerhans to
      restore normoglycaemia following transplantation into the subretinal space of
      pancreatectomized cats. Collagenase digestate of feline pancreas was maintained
      in serum-free tissue culture medium for 1-9 days. Viability of islet-like cell
      clusters (ICC) was assessed with ethidium bromide and fluorescein diacetate
      staining; cell types were identified immunohistochemically. After nine days, the
      ICC were transplanted. We estimated viable ICC in tissue culture at nine days as
      3800 +/- 2000 (mean +/- SD) per pancreas. While numbers of beta cells decreased
      over time in culture, ductal cells increased. Bromodeoxyuridine labelling showed
      no proliferation of beta cells but extensive proliferation of ductal cells.
      Subretinal transplants of cultured ICC in the diabetic cats maintained
      normoglycaemia for up to 12 days, while they provoked massive lymphocyte
      infiltration indicating rejection. Islet transplantation into the feline
      subretinal space temporarily restored normoglycaemia. Our current method of
      culture achieved sufficient reduction of acinar cells but an insufficient yield
      of insulin-producing cells.

PMID- 17018215
TI  - Detection of antibodies to Streptobacillus moniliformis in rats by an immunoblot
      procedure.
AB  - An immunoblot (IB) technique for detecting antibodies to Streptobacillus
      moniliformis in rat sera was evaluated. Immune sera to three S. moniliformis
      strains showed a similar reactivity pattern with both autologous and homologous
      antigens in the 18-87 kDa range. Using a rat S. moniliformis strain as the
      antigen, a similar reactivity pattern was found with sera from rats infected
      experimentally with S. moniliformis and sentinels. Two to five proteins were
      detected in the 32-55 kDa range. Over a period of 2.5 years, 27/133 rat serum
      panels submitted for routine monitoring yielded one or more S. moniliformis
      enzyme-linked immunosorbent assay (ELISA)-positive samples. In one of these 27
      panels, sera showed an IB reactivity pattern resembling that observed with immune
      sera and with sera from infected and exposed rats. S. moniliformis was confirmed
      in the colony by both culture and polymerase chain reaction (PCR). Sera from the
      remaining 26 ELISA-positive serum panels frequently showed activity to a 57 kDa
      antigen but not more than one antigen was detected in the 32-55 kDa range. We
      conclude that the IB can be used as a confirmatory test for the detection of S.
      moniliformis infection in ELISA-positive rats.

PMID- 17018216
TI  - Intraoral cheek fistulae: a refined technique.
AB  - Taste reactivity testing (TRT), which entails infusing a solution into the oral
      cavity of subjects, is used across a wide range of studies. For laboratories
      inexperienced in the conventional technique of implanting cheek fistulae, the
      surgery can be problematic for both the subjects and the experimenter. We have
      proposed a refined method for fistulae implantation that is less invasive,
      thereby reducing the pain and distress of the animals. Using this refined
      technique, we were able to replicate the findings of previous TRT studies, namely
      that a high dose of lithium chloride produces an increase in aversive and a
      decrease in ingestive orofacial and somatic responses. Using indices of health,
      we demonstrate that unlike animals with the conventional method of fistulae
      implantation, subjects that receive the refined technique regain their pre
      surgery body weights rapidly and show no physical signs of discomfort. Additional
      advantages of the refined technique are discussed.

PMID- 17018217
TI  - Surgical procedure for implanting a radiotelemetry transmitter to monitor ECG,
      heart rate and body temperature in small Carassius auratus and Carassius auratus
      gibelio under laboratory conditions.
AB  - Radiotelemetry provides an alternative means of obtaining physiological
      measurements from conscious and freely moving animals, without introducing stress
      artefacts. A surgical procedure is described for implanting radiotelemetry
      transmitters to monitor the electrocardiogram (ECG), heart rate (HR) and body
      temperature (BT) in small goldfish (Carassius auratus; 50-100 g) and Prussian
      carp (Carassius auratus gibelio; 100 g). This type of transmitter is commonly
      implanted in freely moving mice. After surgery and a recovery period of 24 h, the
      ECG, HR and BT were recorded in freely swimming fish within the limitations of
      the aquarium.

PMID- 17018218
TI  - The feasibility of detecting motor and sensory potentials in a sheep model.
AB  - To investigate the characteristics of motor, sensory and sensory-evoked
      potentials (SEPs) of thoracic and lumbar roots, and demonstrate the feasibility
      of assessing axonal regrowth after the neurotization procedure in a sheep model.
      Six adult sheep were anaesthetized and placed in a sternal position. The thoracic
      and lumbar roots from T11 to L5 were identified at their emergence from the
      vertebral foramen and stimulated. Motor and sensory responses were monitored.
      Thoracic and lumbar roots were easily identified in all cases. Motor potentials
      were detected for each stimulated nerve without difficulty. The amplitudes were
      quite variable, ranging from 100 to 5300 microV. Sensory and SEPs were
      satisfactorily recorded in only three of the six animals. Sensory amplitudes also
      varied greatly, ranging from 25 to 120 microV. In three cases, SEPs could not be
      identified due to motor artefacts. The motor pathway after axonal regrowth in
      neurotized lumbar roots might easily be explored by proximal electric stimulation
      of the root, close to the sutured area. Detection of sensory and spinal cord
      evoked potentials might be improved by the use of curve summation techniques.
      Specific axonal tracing holds promise of being a useful technique for examining
      sensory and motor pathway recovery after neurotization in the sheep model.

PMID- 17018219
TI  - Mortality from oral and pharyngeal cancer in Brazil: trends and regional
      patterns, 1979-2002.
AB  - OBJECTIVE: To investigate the trends and regional patterns in mortality from oral
      cancer and pharyngeal cancer in Brazil from 1979 through 2002. METHODS: Data were
      obtained from the Mortality Information System (Sistema de Informacoes sobre
      Mortalidade) database, which is compiled by the Ministry of Health of Brazil.
      Mortality rates were adjusted by gender and age. The Prais-Winsten generalized
      linear regression procedure was used to calculate the annual increase or decrease
      in mortality rates. The time trends for mortality due to oral cancer and to
      pharyngeal cancer were analyzed by specific anatomical site and by region of the
      country (North, Northeast, South, Southeast, and Center-West). RESULTS: In all
      five regions of Brazil over the period studied, oral cancer mortality remained
      stable for both genders, but pharyngeal cancer mortality increased for both
      genders. Mortality from cancer affecting the lips, tongue, gums, mouth floor,
      palate, other parts of the mouth, and tonsils showed a statistically significant
      decrease over the period. However, mortality from cancer affecting the
      oropharynx, hypopharynx, and ill-defined and undefined sites of the oral cavity
      and the pharynx showed a significant increase. Mortality rates for both oral
      cancer and pharyngeal cancer were higher in the South and Southeast regions of
      the country than in Brazil's three other regions. CONCLUSIONS: The relatively
      larger decrease in mortality from cancer affecting the lips, gums, and other
      anatomical sites more easily accessible to clinical inspection suggests a
      possible link between oral and pharyngeal cancer survival and an improved
      provision of health care services in Brazil in recent decades.

PMID- 17018220
TI  - [Burden of rotavirus-related disease among children under five, Colombia, 2004].
AB  - OBJECTIVES: To establish an in-hospital surveillance system for diarrhea in
      children under five, to estimate the burden of rotavirus-related disease, and to
      identify the most common rotavirus genotypes. METHODS: Included in the study were
      children who were hospitalized for serious complications of diarrhea in three
      medical care facilities in Bogota, Barranquilla, and Cali, Colombia. A solid
      phase enzyme-linked immunosorbent assay (ELISA) was used to detect rotavirus, and
      reverse-transcriptase polymerase chain reaction (RT-PCR) was the genotyping
      method employed. The frequencies, central tendency, and dispersion of the
      variables were determined. Stratified analysis and bivariate analysis were
      performed by applying a chi squared test or Fisher's exact test, or a chi squared
      test for trends, depending on the type of data analyzed. Relative risks were
      established. For analyzing trends we performed linear regression and calculated
      correlation coefficients and P values. RESULTS: Between December 2003 and
      November 2004, 893 children were hospitalized in the three participating centers
      included in the study. Of these children, 68% were between 6 and 23 months of
      age; 2.7% of hospitalized patients showed clinical signs of hypovolemic shock,
      and 1.2% died. Only 57% of the mothers had given their children an oral
      rehydration solution before hospitalization. Rotavirus infection was the cause of
      50% of hospitalizations (correlation coefficient [r] > 0.8) and was linked to an
      inability to hold down orally-ingested fluids (relative risk [RR] = 1.45; 95%
      confidence interval [95% CI]: 1.24 to 1.69; P < 0.0000) and to intractable
      vomiting (RR = 1.47; 95% CI: 1.16 to 1.86; P < 0.01). Rotavirus infection led to
      one death per 2 000 children; 16 hospitalizations per 1 000 children, and 631
      medical visits per 1 000 children. A seasonal trend was noted for G1P[8], G2P[4],
      and G3P[8] rotavirus genotypes, and this did not vary as a result of geographic
      distance or differences in temperature, humidity, and rainfall among cities.
      CONCLUSIONS: Rotavirus infection is an important cause of morbidity and mortality
      from diarrhea, particularly during the first years of life, when children are
      more susceptible to serious complications. It is important for prevention
      strategies to have a high impact before 6 months of age, and vaccination against
      rotavirus can be a good complementary intervention strategy. No description was
      found in the international scientific literature of the seasonal variations in
      rotavirus genotypes. It is important to carry out cost-effectiveness studies in
      order to promote the investment of resources in accordance with population needs,
      and to continue surveillance activities so as to better understand how the virus
      behaves.

PMID- 17018221
TI  - [Prevalence of signs and symptoms, associated sociodemographic factors and
      resulting actions in an urban center in southern Brazil].
AB  - OBJECTIVE: To determine the prevalence of signs and symptoms in the adult
      population, the sociodemographic factors associated with them, and the actions
      taken as a result of these symptoms, according to sex. METHODS: A population
      based cross-sectional study was carried out in the city of Rio Grande (state of
      Rio Grande do Sul), Brazil, in 2000. We interviewed 1 259 people > or = 15 years
      of age. Data were collected using a structured questionnaire containing 18
      symptoms in addition to sociodemographic questions. The prevalence of symptoms
      and prevalence ratios for sex, age, and socioeconomic status were estimated after
      alternately adjusting for these variables. The actions resulting from the
      presence of symptoms were also analyzed for each sex. RESULTS: Mean age was 40.33
      years (53.9% were women). The most prevalent symptom was headache (55.4%). Joint
      pain, insomnia, constipation, high blood pressure, and shortness of breath
      increased with age. The following were more prevalent among the lower social
      classes: headache, nervousness, joint and back pain, insomnia and depression,
      high blood pressure, chest pain, and shortness of breath. A total of 4 424 health
      problems were reported (an average of 3.25 per person); 60.2% did not generate
      any action, 31.6% resulted in self-medication, and 8.2% resulted in a visit to a
      medical facility. Headache, nervousness, joint and back pain, insomnia,
      depression, constipation, high blood pressure, chest pain, and shortness of
      breath were significantly higher in women, whereas cough was significantly more
      prevalent in men. Women and men took similar actions in the presence of signs and
      symptoms. CONCLUSION: It is necessary to establish health policies that lay an
      emphasis on mental health and education for self care and on those symptoms that
      signal the need to go to a health facility. It is also necessary to study the
      role of social class in determining health behavior and the choice to seek care.

PMID- 17018222
TI  - [Women's empowerment and life expectancy at birth in Mexico].
AB  - OBJECTIVES: To assess the effect of women's empowerment (WE) on life expectancy
      at birth (LEB) in the federative states of Mexico and to compare the results of
      measuring WE with various compound indicators that reflect, to a greater or
      lesser degree, an individual or population focus. METHODS: This was an ecological
      study conducted in Mexico's 32 federative states. We estimated the correlations
      between overall and sex-specific LEB on the one hand, and a measure of gender
      empowerment (MGE), the index of women's ability to make decisions within the
      household (WADH), the index of women's autonomy (IWA), income inequality, certain
      aspects of the physical environment, the proportion of the population who spoke
      an indigenous language, and the net migratory rate on the other. By using robust
      regressions, we studied the effect on LEB of MGE, IWA, and WADH, after mutually
      adjusting for other independent variables. RESULTS: A very strong inverse
      correlation (-0.93) was found between overall LEB and factors of the physical
      environment linked to population vulnerability and biodiversity. Significant
      direct and inverse correlations were also found between LEB on the one hand and
      WADH, IWA, net migratory rate, the percentage of the population that spoke an
      indigenous language, and the Gini coefficient on the other. Multiple robust
      regressions showed inverse associations between MGE and LEB in women (beta: 
      1.44; 95% confidence interval [95% CI]: -2.71 to -0.17). WAI was positively
      associated with LEB in men (beta: 0.88; 95% CI: 0.01 to 1.75) and women (beta:
      0.66; 95% CI: 0.03 to 1.30). CONCLUSION: The use of MGE as a surrogate for WE
      failed to reveal a positive effect of WE on LEB in Mexico. It is necessary to
      review the components that make up MGE and the relevance of using such a measure
      in different contexts. WAI showed a greater association with LEB and its effect
      was greater among men. This indicator made it possible to measure WE in Mexico
      and its use is recommended, as long as there are no other indicators available
      for capturing more effectively all the components that affect WE.

PMID- 17018223
TI  - Seroprevalence of dengue virus antibodies in asymptomatic Costa Rican children,
      2002-2003: a pilot study.
AB  - OBJECTIVES: Since 1993 dengue has become more frequent in Costa Rica. Adults have
      been the most affected population, while children have remained virtually
      unharmed. So far no studies have investigated how many asymptomatic children have
      been affected by this virus. This pilot study documents the seroprevalence,
      measured as the presence of IgG antibodies, of dengue virus in asymptomatic
      children from two different geographical areas. METHODS: This descriptive,
      prospective epidemiologic study compared the presence of antibodies in children
      who live in a coastal region of a tropical country where dengue is endemic, and
      an inland area where dengue is not endemic. An enzyme-linked immunosorbent assay
      was used to test the serum for dengue virus IgG antibodies. None of the children
      had a prior history of dengue, fever, immunosuppressive therapy or underlying
      disease. RESULTS: During the period from July 2002 to July 2003, 103 children
      were recruited from each area. In the costal region we found a seroprevalence of
      36.9%. In the inland area seroprevalence was 2.9%. CONCLUSIONS: We found a
      substantial number of asymptomatic infections in Costa Rican children. This
      greatly increases the risk of dengue hemorrhagic fever or dengue shock syndrome
      in these children, in whom previous dengue infection had gone undetected.
      Preventive efforts should be targeted at the costal region due to the higher
      prevalence in this area.

PMID- 17018224
TI  - [Health priorities in Brazil in the 1990s: three policies, many lessons].
AB  - This paper, which focuses on the Brazilian Ministry of Health's agenda as the
      national health authority between 1990 and 2002, identifies and analyzes Ministry
      priorities. Three main policies were identified for the period: decentralization,
      establishment of a family health program, and the policy to combat AIDS. In
      general, the initial design of these policies was consistent with the guidelines
      of the Brazilian public health system (SUS). However, discrepancies were found
      between the universalistic agenda of the Brazilian health reform carried out in
      the 1980s and the hegemonic agenda of state reform that prevailed in the country
      in the 1990s, which had liberal roots and did not favor the expansion of
      government actions and comprehensive social policies. Within this unfavorable
      political and economic context, the development of specific health policies
      prioritized by the Brazilian Ministry of Health revealed unsolved problems and
      gaps in the public health system and limitations in the Ministry's ability to
      exercise its role as national health authority.

PMID- 17018225
TI  - Regional immunization programs as a model for strengthening cooperation among
      nations.

PMID- 17018226
TI  - [Preventing deaths from dengue: a space and challenge for primary health care].
AB  - Dengue is an arthropod-borne viral disease whose frequency has increased steadily
      in the Americas over the past 25 years. The type of dengue that carries the
      highest mortality is the clinical variant known as dengue hemorrhagic
      fever/dengue shock syndrome (DHF/DSS). Even though no vaccine or drug against the
      disease is available, successful management consists of preventing serious
      illness through patient follow-up and monitoring danger signals so as to be able
      to initiate aggressive intravenous rehydration and prevent shock or treat it
      early and successfully. These measures are also useful in preventing other
      complications, such as massive hemorrhage, disseminated intravascular
      coagulation, multiple organ failure, and respiratory failure due to non
      cardiogenic pulmonary edema. Primary health care (PHC) settings and the community
      are ideal spaces for this type of preventive management based on health education
      and active case detection. It involves training all medical and nursing staff,
      students, and community health workers, as well as reorganizing health care in
      PHC units and hospitals and redistributing available resources during a dengue
      epidemic.

PMID- 17018227
TI  - A comparison of the cost-effectiveness of five strategies for the prevention of
      non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a
      systematic review with economic modelling.
AB  - OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs
      and cost-effectiveness of four strategies for the prevention of non-steroidal
      anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox
      1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus
      proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2
      NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs).
      DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant
      studies were selected, assessed and analysed. Pooled relative risk ratios (RR)
      from the systematic review were combined with up-to-date UK resource use and unit
      costs data in an incremental economic analysis. A probabilistic decision-analytic
      model was designed and populated with data to carry out incremental economic
      analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the
      outcome measure, endoscopic ulcer or serious GI event averted, against total
      cost, and non-parametric bootstrapping was used to simulate variance of these
      ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which
      included 76,322 participants) only 138 deaths and 248 serious GI events were
      reported. Seven comparisons were judged to be at low risk of bias. Comparing the
      gastroprotective strategies against placebo, there was no evidence of
      effectiveness of H2RAs against any primary outcomes (few events reported), PPIs
      may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI)
      0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57,
      95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2
      'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to
      0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI
      0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All
      strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers.
      There were only 12 direct comparisons between gastroprotective strategies. All
      they suggest is that Cox-2 preferentials are better than misoprostol for
      preventing GI complications. Indirect comparisons suggested that PPIs may prevent
      symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For
      prevention of endoscopic ulcers PPIs and misoprostol appear more successful than
      H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head
      to-head published economic analyses with regard to the main gastroprotective
      strategies. There were generally insufficient data with regards to cardiac or
      renal outcomes, serious GI outcomes or life-years gained to populate the mode.
      Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared
      with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to
      804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds
      (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2
      specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of
      endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness
      acceptability analysis showed a 95% probability that this combination was less
      costly and more effective. Cost-effectiveness acceptability frontiers showed that
      if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic
      ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is
      willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol.
      Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and
      over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is
      never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1
      NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in
      the older age group. Some conclusions were associated with high levels of
      uncertainty. CONCLUSIONS: Although there is a very large body of evidence
      comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the
      other types of gastroprotectors or by studies directly comparing active
      gastroprotective strategies. This lack of direct comparisons led to the use of
      indirect comparisons to help understand the relative efficacy of these
      strategies. Indirect evidence in itself is weak and was also hampered by lack of
      evidence in the underlying studies (where the gastroprotectors were compared with
      placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID
      plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in
      patients requiring long-term NSAID therapy. All strategies other than Cox-2
      selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1
      alone. The economic analysis suggests that there may be a case for prescribing
      H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is
      associated with a greater cost and GI side-effects which may be unacceptable for
      patients. However, when assessing serious GI events, the economic analysis is
      sufficiently weakened by the data available as to render clear practice
      recommendations impossible. Further large, independent RCTs directly comparing
      various gastroprotective strategies are needed. These should report items such as
      major outcomes, primary data, adverse events, assessment of practice and patient
      preference.

PMID- 17018228
TI  - The effectiveness and cost-effectiveness of computed tomography screening for
      coronary artery disease: systematic review.
AB  - OBJECTIVES: To assess the clinical and cost-effectiveness of computed tomography
      (CT) screening for asymptomatic coronary artery disease; also to establish
      whether coronary artery calcification (CAC) predicts coronary events and adds
      anything to risk factor scores, and whether measuring CAC changes treatment. DATA
      SOURCES: Main electronic databases were searched up to 2005, with a MEDLINE
      update in February 2006. METHODS: A systematic review of screening studies and
      economic evaluations was carried out. Studies were included in the review if
      screening for coronary heart disease was the principal theme of the study, and if
      data were provided that allowed comparison of CT screening with current practice,
      which was taken to be risk factor scoring. Mismatches between CAC scores and risk
      factor scoring were of particular interest. A review of the case for screening
      against the criteria used by the National Screening Committee (NSC) for assessing
      screening programmes was also undertaken. RESULTS: No randomised control trials
      (RCTs) were found that assessed the value of CT screening in reducing cardiac
      events. Seven studies were identified that assessed the association between CAC
      scores on CT and cardiac outcomes in asymptomatic people and included 30,599
      people. Six used electron-beam CT. The relative risk of a cardiac event was 4.4
      if CAC was present, compared to there being no CAC. As CAC score increased, so
      did the risk of cardiac events. The correlation between CAC and cardiac risk was
      consistent across studies. There was evidence that CAC scores varied among people
      with the same Framingham risk factor scores, and that within the same Framingham
      bands, people with higher CAC scores had significantly higher cardiac event
      rates. This applied mainly when the CAC scores exceeded 300. There was little
      difference in event rates among the groups with no CAC, and scores of 1-100 and
      101-300. In one study, CAC score was a better predictor of cardiac events than
      the Framingham risk scores. No studies were found that showed whether the
      addition of CAC scores to standard risk factor assessment would improve outcomes.
      There were reports from two observational studies that lowering of low-density
      lipoprotein cholesterol to about 3 mmol/l; or below with statin treatment
      modestly reduced CAC scores, but this was not confirmed in two RCTs. In three
      studies examining whether knowledge of CAC scores would affect compliance with
      lifestyle measures, perception of risk was affected, but it did not improve
      smoking cessation rates, although it did increase anxiety. There were a few
      economic studies of CT screening for heart disease, which provided useful data on
      costs of scans, other investigations and treatment, but relied on a number of
      assumptions, and were unable to provide definitive answers. One modelling study
      estimated that adding CT screening to risk factor scoring, and only giving
      statins to those with CAC score over 100, would save money, based on a cost per
      CT screen of US$400 and statin costs of US$1000 per annum per patient. However,
      the arrival of generic statins has reduced the price dramatically, and these
      savings no longer apply. CONCLUSIONS: CT examination of the coronary arteries can
      detect calcification indicative of arterial disease in asymptomatic people, many
      of whom would be at low risk when assessed by traditional risk factors. The
      higher the CAC score, the higher the risk. Treatment with statins can reduce that
      risk. However, CT screening would miss many of the most dangerous patches of
      arterial disease, because they are not yet calcified, and so there would be false
      negative results: normal CT followed by a heart attack. There would also be false
      positive results in that many calcified arteries will have normal blood flow and
      will not be affected by clinically apparent thrombosis: abnormal CT not followed
      by a heart attack. For CT screening to be cost-effective, it has to add value
      over risk factor scoring, by producing sufficient additional information to
      change treatment and hence cardiac outcomes, at an affordable cost per quality
      adjusted life-year. There was insufficient evidence to support this. Most of the
      NSC criteria were either not met or only partially met. It would be useful to
      have more data on the distributions of risk scores and CAC scores in asymptomatic
      people, and the level of concordance between risk factor and CAC scores, the risk
      of cardiac events per annum according to CAC score and risk factor scores,
      information on the acceptability of CT screening, after information about the
      radiation dose, and an RCT of adding CT screening to current risk factor-based
      practice.

PMID- 17018229
TI  - What are the clinical outcome and cost-effectiveness of endoscopy undertaken by
      nurses when compared with doctors? A Multi-Institution Nurse Endoscopy Trial
      (MINuET).
AB  - OBJECTIVES: To compare the clinical outcome and cost-effectiveness of doctors and
      nurses undertaking upper and lower gastrointestinal endoscopy. DESIGN: The study
      was a pragmatic randomised controlled trial. Zelen's randomisation before consent
      was used to minimise distortion of existing practice in the participating sites.
      An economic evaluation was conducted alongside the trial, assessing the relative
      cost-effectiveness of nurses and doctors. SETTING: The study was undertaken in 23
      hospitals in England, Scotland and Wales. In six hospitals nurses undertook both
      upper and lower gastrointestinal endoscopy, yielding a total of 29 'centres'. The
      study was coordinated and managed from Swansea. Randomisation, data management
      and analysis were undertaken at York. Analysis was by intention-to-scope.
      PARTICIPANTS: Sixty-seven doctors and 30 nurses took part in the study. Of 4964
      potentially eligible patients, 4128 (83%) were randomised. Of these, 1888 (45%)
      were recruited to the study from 29 July 2002 to 30 June 2003. INTERVENTIONS: The
      procedures under study were diagnostic upper gastrointestinal endoscopy and
      flexible sigmoidoscopy undertaken by nurses or doctors, with or without sedation,
      using the preparation, techniques and protocols of participating hospitals. MAIN
      OUTCOME MEASURES: Primary outcome measure was the Gastrointestinal Symptom Rating
      Questionnaire (GSRQ). The secondary outcome measures were EuroQol (EQ5D),
      Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ), State-Trait Anxiety
      Inventory (STAI), cost-effectiveness, immediate and delayed complications,
      quality of examination by blinded assessment of endoscopic video recordings,
      quality of procedure reports, patients' preferences for operator 1 year after
      endoscopy, and new diagnoses at 1 year. RESULTS: The two groups were well matched
      at baseline for demographic and clinical characteristics. Significantly more
      patients changed from a planned endoscopy by a doctor to a nurse than vice versa,
      mainly for staffing reasons. There was no significant difference between the two
      groups in the primary or secondary outcome measures at 1 day, 1 month or 1 year
      after endoscopy, with the exception of patient satisfaction at 1 day, which
      favoured nurses. Nurses were significantly more thorough in the examination of
      stomach and oesophagus, but no different from doctors in the examination of
      duodenum and colon. There was no significant difference in costs to the NHS or
      patients, although doctors cost slightly more. Although quality of life measures
      showed improvement in some scores in the doctor group, this did not reach
      traditional levels of statistical significance. Even so, the economic evaluation,
      taking account of uncertainty in both costs and quality of life, suggests that
      endoscopy by doctors has an 87% chance of being more cost-effective than
      endoscopy by nurses. CONCLUSIONS: There is no statistically significant
      difference between doctors and nurses in their clinical effectiveness in
      diagnostic endoscopy. However, nurses are significantly more thorough in the
      examination of oesophagus and stomach, and patients are significantly more
      satisfied after endoscopy by a nurse. Endoscopy by doctors is associated with
      better outcome at 1 year at higher cost, but overall is likely to be cost
      effective. Further research is needed to evaluate the clinical outcome and cost
      effectiveness of nurses undertaking a greater role in other settings, to monitor
      the cost-effectiveness of nurse endoscopists as they become more experienced and
      to assess, the effect of increasing the number of nurse endoscopists on waiting
      times for patients, and the career implications and opportunities for nurses who
      become trained endoscopists. Evaluation of the clinical outcome and cost
      effectiveness of diagnostic endoscopy for all current indications is also needed.

PMID- 17018230
TI  - Leukocyte count is an independent predictor for risk of acute myocardial
      infarction in middle-aged Japanese men.
AB  - BACKGROUND: Leukocyte count is recognized as an inflammatory marker and a
      predictor of cardiovascular events. However, it is uncertain whether the
      contribution of leukocyte count to the risk of cardiovascular disease is
      independent of smoking. METHODS: The subjects were 4492 male employees aged 40-59
      years who worked for nine companies in Osaka. RESULTS: After 9-year follow-up, 40
      acute myocardial infarction and 26 ischemic stroke events occurred. Age-adjusted
      relative risk of acute myocardial infarction in the highest versus lowest
      quartiles of leukocyte count was 6.0 (95% CI, 1.8-20.5, P for trend <0.001) and
      the multivariable relative risk adjusted for smoking and other conventional
      cardiovascular risk factors was 3.7 (1.0-13.4, P for trend=0.01). The association
      between leukocyte count and the risk of acute myocardial infarction was also
      observed among both current smokers and nonsmokers. The positive association
      between leukocyte count and the risk of ischemic stroke was weak and did not
      reach statistical significance. CONCLUSIONS: Leukocyte count is a predictor of
      acute myocardial infarction among Japanese middle-aged men, both in smokers and
      nonsmokers.

PMID- 17018231
TI  - Simultaneous determination of 11 characteristic components in three species of
      Curcuma rhizomes using pressurized liquid extraction and high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatography coupled with diode array detection (HPLC
      DAD) and pressurized liquid extraction was developed for simultaneous
      quantitative determination of 11 characteristic compounds, including curcumenone,
      curcumenol, neocurdione, curdione, isocurcumenol, furanodienone, curcumol,
      germacrone, curzerene, furanodiene and beta-elemene, in rhizomes of three species
      of Curcuma. The analysis was performed on an ODS C18 column. The mobile phase
      consisted of (A) water and (B) acetonitrile using a gradient elution. The peaks
      were monitored at both 214 nm and 256 nm. All calibration curves showed good
      linearity (r2 > 0.9996) within test ranges. This method showed good repeatability
      for the quantification of these eleven components in three species Curcuma
      rhizomes with intra- and inter-day variations of less than 1.57% and 1.98%,
      respectively. The validated method was successfully applied to quantify 11
      investigated components in eighteen samples of three species of Curcuma, which is
      helpful to control their quality.

PMID- 17018232
TI  - True and false reversal of the elution order of barbiturates on a bonded
      cellulose-based chiral stationary phase.
AB  - A set of racemic N-alkylated barbiturates were investigated for their direct
      enantioselective HPLC separation on a new chiral stationary phase (CSP)
      containing cellulose tris(3,5-dimethylphenylcarabamate) immobilized onto silica
      gel (Chiralpak IB) and its coated version (Chiralcel OD). They were online
      detected by UV and optical rotation detectors to trace the elution order of their
      enantiomers. Surprisingly, examples of false and true reversal of the elution
      order of enantiomers of barbiturates were observed and reported.

PMID- 17018233
TI  - Isolation of tomato pectin methylesterase and polygalacturonase on monolithic
      columns.
AB  - An improved cation-exchange chromatographic procedure on Convective Interaction
      Media (CIM, BIA Separations, Ljubljana, Slovenia) short monolithic methacrylate
      disk columns was used for the isolation of salt-independent pectin methylesterase
      (PME; EC 3.1.1.11) isoform and endo-polygalacturonase PG1 (PG, EC 3.2.1.15) from
      ripe tomato fruit extract after studying the chromatographic conditions including
      type of disk, binding buffer, pH, eluent composition and different gradients.
      Between 10 and 20 microg of proteins gave reliable chromatograms. Both
      carboxymethyl (CM) and sulfonyl (SO3) disks were equally suitable for the
      fractionation of tomato extract using the new gradient, but only CM disk was
      appropriate for further purification of the PME and PG fractions, and provided
      fast and sharp separation of proteins. The isolation of pure PG1 could be
      achieved only by addition of 20% of acetonitrile to the mobile phase. About 200
      microg of proteins were loaded at one chromatographic run at the fractionation
      and purification. Determination of the molecular weights of the separated
      proteins showed that dimer of salt-independent PME isoform was formed in
      concentrated solutions of the enzyme but dissociated upon dilution of the
      solution. From 6 kg of fresh tomato flesh, 28 mg of purified salt-independent
      PME, 12.5mg of purified and active PG1 and 4 mg of PG2 fraction contaminated with
      salt-dependent PME isoform were obtained by means of semi-preparative
      chromatography on CIM disks.

PMID- 17018234
TI  - Quantitative determination of folic acid in multivitamin/multielement tablets
      using liquid chromatography/tandem mass spectrometry.
AB  - Two different isotope-dilution liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) methods for the quantitative determination of folic acid (FA) in
      multivitamin/multielement tablets are reported. These methods represent distinct
      improvements in terms of speed and specificity over most existing microbiological
      and chromatographic methods for the determination of FA in dietary supplements.
      The first method utilizes an aqueous/organic-based extraction solvent combined
      with positive-ion mode LC/MS/MS detection of protonated [M + H]+ FA molecules and
      the second method utilizes a pure aqueous-based extraction solvent combined with
      negative-ion mode LC/MS/MS detection of deprotonated [M - H]- FA molecules. The
      LC/MS/MS methods exhibit comparable linear dynamic ranges (> or =3 orders of
      magnitude), limits of detection (0.02 ng on-column) and limits of quantification
      (0.06 ng on-column) for FA. Two methods employing different extraction and
      different MS detection modes were developed to allow method cross-validation.
      Successful validation of each measurement procedure supports the use of either
      method for the certification of FA levels in dietary supplements. The accuracy
      and precision of each measurement procedure were evaluated by applying each
      method to the quantitative determination of FA in a NIST standard reference
      material (NIST SRM 3280 multivitamin/multielement tablets). The FA measurement
      accuracy for both methods was > or =95% (based on the manufacturer's assessment
      of the FA level in SRM 3280) with corresponding measurement precision values (%
      RSD) of approximately 1%.

PMID- 17018235
TI  - Risk factors for infection of the diabetic foot with multi-antibiotic resistant
      microorganisms.
AB  - AIM: To investigate the risk factors for infection of the diabetic foot with
      multidrug resistant microorganisms. METHODS: Amongst 102 diabetic patients with
      evidence of soft tissue infection of the foot who presented to our health center
      over a three year period, we investigated risk factors that might be predictive
      of multi-antibiotic resistance of the infecting organism. RESULTS: Of 102
      patients with a diabetic foot wound, bacteria were cultured from 73, yielding a
      total of 104 isolates. The number of multidrug resistant isolates was 42 from 36
      cases and the number of isolates other than multidrug resistant ones was 62 from
      37 cases. Previous antibiotic therapy (p=0.002) and its duration (p=0.0001),
      frequency of hospitalization for the same wound (p=0.000), duration of hospital
      stay (p=0.000) and osteomyelitis (p=0.001) were significant risk factors for
      infections with multidrug resistant microorganisms. CONCLUSION: In conclusion, an
      appropriate antibiotic should be initiated promptly, wound perfusion should be
      effective, duration of hospital stay should be as short as possible and optimum
      hygiene should be provided during wound care to prevent infections of diabetic
      foot wound with multidrug resistant microorganisms.

PMID- 17018236
TI  - The rostral anterior cingulate cortex modulates depression but not anxiety
      related behaviour in the rat.
AB  - A growing body of functional imaging studies suggests that human depression and
      anxiety symptoms are associated with functional abnormalities in the circuitry
      formed by the rostral anterior cingulate cortex (rACC) and its direct limbic and
      paralimbic connections. In rodents however, the role of the rACC (rCG1/rCG2)
      remains unknown in depression-related behaviours and elusive in acute anxiety. In
      order to address this, we specifically lesioned the rat rCG1/rCG2, and assessed
      the behavioural outcome using a modified forced swim test (FST) and the elevated
      plus maze (EPM), tests for depression and anxiety related behaviours
      respectively. Lesions of the rostral anterior cingulate cortex significantly
      increased the time spent immobile in the FST without affecting climbing or
      swimming performances, suggesting a pro-depressant effect. On the contrary, none
      of the parameters measured in the EPM was affected by the lesion. These data
      point to an involvement of the rCG1/rCG2 in depression-related coping behaviours.

PMID- 17018237
TI  - Anastrozole improved testosterone-induced impairment acquisition of spatial
      learning and memory in the hippocampal CA1 region in adult male rats.
AB  - Neurohormones like testosterone and estrogen have an important role in learning
      and memory. Many biological effects of androgens in the brain require the local
      conversion of these steroids to an estrogen. The current research has conducted
      to assess the effect of testosterone, estrogen and aromatase inhibitor
      (anastrozole) on spatial discrimination of rats, using Morris water maze and also
      the pathway of the effect of testosterone by using anastrozole. Adult male rats
      were bilaterally cannulated into CA1 region of hippocampus and divided into 15
      groups. Different groups received DMSO 0.5 microl and DMSO 0.5 microl + DMSO 0.5
      microl as control groups and different doses of testosterone enanthate (TE) (20,
      40 and 80 microg/0.5 microl), estradiol valerat (EV) (1, 2.5, 5, 10, and 15
      microg/0.5 microl), anastrozole (An) (0.25, 0.5, 1 microg/0.5 microl), TE 80
      microg/0.5 microl + anastrozole 0.5 microg/0.5 microl and EV 15 microg/0.5 microl
      + anastrozole 0.5 microg/0.5 microl all days before training. TE and EV were
      injected 30-35 min before training and anastrozole was injected 25-30 min before
      training. Our results have shown both TE 80 microg/0.5 microl and EV 15
      microg/0.5 microl groups increase in escape latency and traveled distance to find
      invisible platform. Also we have shown that anastrozole dose dependently
      decreases escape latency and traveled distance. We resulted that both TE and EN
      impaired acquisition of spatial learning and memory but anastrozole improved it.
      Anastrozole also could be buffered TE-induced impairment effect but not EV.

PMID- 17018238
TI  - The role of Leishmania enriettii multidrug resistance protein 1 (LeMDR1) in
      mediating drug resistance is iron-dependent.
AB  - In parasitic protozoan Leishmania enriettii, the role of a multidrug resistance
      (mdr) gene LeMDR1 (L. enriettii multidrug resistance 1) in mediating vinblastine
      resistance has been previously demonstrated by association, transfection and
      "gene knockout" studies. LeMDR1 has been shown to be located intracellularly and
      it was proposed to mediate drug resistance by sequestering drugs into
      intracellular organelles rather than by active efflux. Here we compared LeMDR1
      overexpressed cell lines (Vint3 and V160), wild type (Le) and LeMDR1 "double
      knockout" mutant (LeMDR1-/-) and demonstrated that LeMDR1 gene copy number was
      associated with (1) higher level of intracellular iron, (2) increased sensitivity
      to an iron-dependent antibiotic, streptonigrin and (3) increased enzyme activity
      of an iron-sulfur-containing mitochondrial enzyme, aconitase. This result
      suggests that the normal function of LeMDR1 is related to mitochondrial iron
      homeostasis. To test such hypothesis, we have used the LeMDR1-overexpressing
      mutant V160 and LeMDR1-/- mutant to determine how iron level can affect its
      resistance level to drugs targeting either cytosol (vinblastine) or mitochondria
      (rhodamine 123 and pentamidine). It was found that the resistance level of V160
      to vinblastine can be increased by iron whereas resistance to both rhodamine 123
      and pentamidine can be increased by iron depletion and vice versa. Iron treatment
      can potentiate rhodamine 123 and pentamidine accumulation whereas iron
      deprivation can cause the reduction of rhodamine 123 accumulation. Our result
      highly suggests that LeMDR1's function in mediating drug resistance is iron
      dependent.

PMID- 17018239
TI  - Avian reovirus: structure and biology.
AB  - Avian reoviruses are important pathogens that cause considerable losses to the
      poultry industry, but they have been poorly characterized at the molecular level
      in the past, mostly because they have been considered to be very similar to the
      well-studied mammalian reoviruses. Studies performed over the last 20 years have
      revealed that avian reoviruses have unique properties and activities, different
      to those displayed by their mammalian counterparts, and of considerable interest
      to molecular virologists. Notably, the avian reovirus S1 gene is unique, in that
      it is a functional tricistronic gene that possesses three out-of-phase and
      partially overlapping open reading frames; the identification of the mechanisms
      that govern the initiation of translation of the three S1 cistrons, and the study
      of the properties and activities displayed by their encoded proteins, are
      particularly interesting areas of research. For instance, avian reoviruses are
      one of the few nonenveloped viruses that cause cell-cell fusion, and their
      fusogenic phenotype has been associated with a nonstructural 10 kDa transmembrane
      protein, which is expressed by the second cistron of the S1 gene; the small size
      of this atypical fusion protein offers an interesting model for studying the
      mechanisms of cell-cell fusion and for identifying fusogenic domains. Finally,
      avian reoviruses are highly resistant to interferon, and therefore they may be
      useful for investigating the mechanisms and strategies that viruses utilize to
      counteract the antiviral actions of interferons.

PMID- 17018240
TI  - Only through the brain nuclei, arginine vasopressin regulates antinociception in
      the rat.
AB  - The effect of arginine vasopressin (AVP) on rat antinociception was investigated.
      Intraventricular injection of 50 or 100 ng AVP dose-dependently increased the
      pain threshold; in contrast, intraventricular injection of 10 microl anti-AVP
      serum decreased the pain threshold; both intrathecal injection of 200 ng AVP or
      10 microl anti-AVP serum and intravenous injection of 5 microg AVP or 200 microl
      anti-AVP serum did not influence the pain threshold. Pain stimulation reduced AVP
      concentration in hypothalamic paraventricular nucleus (PVN), and elevated AVP
      concentration in hypothalamic supraoptical nucleus (SON) and periaqueductal gray
      (PAG), but no change in AVP concentration was detected in pituitary, spinal cord
      and serum. The results indicated that AVP regulation of antinociception was
      limited to the brain nuclei.

PMID- 17018241
TI  - TFF3-peptide increases transepithelial resistance in epithelial cells by
      modulating claudin-1 and -2 expression.
AB  - TFF3 plays an important role in the protection and repair of the gastrointestinal
      mucosa. The molecular mechanisms of TFF function, however, are still largely
      unknown. Increasing evidence indicates that apart from stabilizing mucosal mucins
      TFF3 induces cellular signals that modulate cell-cell junctions of epithelia. In
      transfected HT29/B6 and MDCK cells stably expressing FLAG-tagged human TFF3 we
      have recently shown that TFF3 down-regulates E-cadherin, impairs the function of
      adherens junctions and thus facilitates cell migration in wounded epithelial cell
      layers. Here we investigate TFF3-induced effects on the composition and function
      of tight junctions in these cells. TFF3 increased the cellular level of
      tightening claudin-1 and decreased the amount of claudin-2 known to form cation
      selective channels. Expression of ZO-1, ZO-2 and occludin was not altered. The
      change in claudin-1 and -2 expression in TFF3-expressing HT29/B6 cells was
      accompanied by an increase in the transepithelial resistance in confluent
      monolayers of these cells. These data suggest that TFF3 plays a role in the
      regulation of intestinal barrier function by altering the claudin composition
      within tight junctions thus decreasing paracellular permeability of the
      intestinal mucosa.

PMID- 17018242
TI  - Beta-amyloid peptide toxicity in organotypic hippocampal slice culture involves
      Akt/PKB, GSK-3beta, and PTEN.
AB  - In the present study we investigated the toxicity induced by exposing organotypic
      slice culture to beta-amyloid peptide 25-35 (25microM) for 1, 3, 6, 12, 24 and
      48h. To elucidate a mechanism involved in its toxicity, we studied the PI3-K cell
      signaling pathway, particularly Akt/PKB, GSK-3beta, and PTEN proteins. Cell death
      was quantified by propidium iodide uptake and proteins were analyzed by
      immunoblotting. Our results showed a significant cell death after 48h of beta
      amyloid 25-35 peptide exposition. The exposition of cultures to beta-amyloid
      peptide resulted in an increase in the phosphorylation state of Akt and GSK-3beta
      proteins after 6h, followed by a decrease of the phosphorylation state of these
      proteins after 12h of exposition. However, after 24h of peptide treatment, the
      phosphorylation of GSK-3beta presented a new increase while the phosphorylation
      of Akt remained down. The immunocontent of the PTEN protein, an indirect Akt
      phosphatase, increased after 24 and 48h of beta-amyloid exposition. These results
      suggest an involvement of Akt dephosphorylation/inactivation in the toxicity
      induced by the beta-amyloid 25-35 peptide in organotypic slice hippocampal
      culture, probably induced by increasing PTEN immunocontent. Taken together, our
      results provide more information about the molecular mechanisms involved on beta
      amyloid peptide toxicity.

PMID- 17018243
TI  - Impact of humic substances on the aqueous solubility, uptake and bioaccumulation
      of platinum, palladium and rhodium in exposure studies with Dreissena polymorpha.
AB  - Zebra mussels (Dreissena polymorpha) were exposed to different types of water
      containing PGE salts (PtCl4, PdSO4, RhCl3) to investigate the influence of humic
      substances on the aqueous solubility, uptake and bioaccumulation of noble metals.
      The results showed a time dependent decrease of the aqueous PGE concentrations in
      tank water for all groups. This could mainly be related to non-biological
      processes. The aqueous solubility of Pd and Rh was higher in humic water compared
      with non-chlorinated tap water, whereas Pt showed opposing results. Highest metal
      uptake rates and highest bioaccumulation plateaus were found for Pd, followed by
      Pt and Rh. Pd uptake and bioaccumulation was significantly hampered by humic
      substances, whose presence appear to increase Pt uptake and bioaccumulation. No
      clear trend emerged for Rh. Differences in effects of humic matter among the PGE
      may be explained by formation of metal complexes with different fractions of
      humic substances.

PMID- 17018244
TI  - Removal of phenol and chlorophenols from water with reusable dye-affinity hollow
      fibers.
AB  - Reactive Green HE 4BD carrying polyamide hollow fibers were investigated as dye
      affinity adsorbents for removal of chlorophenols (i.e., phenol, o-chlorophenol, p
      chlorophenol and 2,4,6-trichlorophenol). Adsorption rates of chlorophenols were
      very high. Equilibrium was achieved in about 30 min. The applicability of two
      kinetic models including pseudo-first order and pseudo-second order model was
      estimated on the basis of comparative analysis of the corresponding rate
      parameters, equilibrium capacity and correlation coefficients. Results suggest
      that chemisorption process could be the rate-limiting step in the adsorption
      process. The maximum adsorption values of chlorophenols onto the Reactive Green
      HE 4BD carrying hollow fibers were 145.9 micromol/g for phenol, 179.2 micromol/g
      for 2,4,6-trichlorophenol, 194.5 micromol/g for p-chlorophenol and 202.8
      micromol/g for o-chlorophenol. The affinity order was as follows: o
      chlorophenol>p-chlorophenol>2,4,6-trichlorophenol>phenol. The adsorption capacity
      of chlorophenols decreased with increasing pH. Desorption of chlorophenols was
      achieved using methanol solution (30%, v/v). The Reactive Green HE 4BD-carrying
      hollow fibers are suitable for repeated use for more than 10 cycles without
      noticeable loss of adsorption capacity.

PMID- 17018245
TI  - Large hydrocarbon fuel pool fires: physical characteristics and thermal emission
      variations with height.
AB  - In a recent paper [P.K. Raj, Large LNG fire thermal radiation-modeling issues and
      hazard criteria revisited, Process Safety Progr., 24 (3) (2005)] it was shown
      that large, turbulent fires on hydrocarbon liquid pools display several
      characteristics including, pulsating burning, production of smoke, and reduced
      thermal radiation, with increasing size. In this paper, a semi-empirical
      mathematical model is proposed which considers several of these important fire
      characteristics. Also included in this paper are the experimental results for the
      variation of the fire radiance from bottom to top of the fire (and their
      statistical distribution) from the largest land spill LNG pool fire test
      conducted to date. The purpose of the model described in this paper is to predict
      the variation of thermal radiation output along the fire plume and to estimate
      the overall thermal emission from the fire as a function its size taking into
      consideration the smoke effects. The model utilizes experimentally measured data
      for different parameters and uses correlations developed from laboratory and
      field tests with different fuels. The fire dynamics and combustion of the fuel
      are modeled using known entrainment and combustion efficiency parameter values.
      The mean emissive power data from field tests are compared with model
      predictions. Model results for the average emissive powers of large, hypothetical
      LNG fires are indicated.

PMID- 17018246
TI  - Neural correlates of fast stimulus discrimination and response selection in top
      level fencers.
AB  - Flexible adaptation of behaviour is highly required in some sports, such as
      fencing. In particular, stimulus discrimination and motor response selection and
      inhibition processes are crucial. We investigated the neural mechanisms
      responsible for fencers' fast and flexible behaviour recording event-related
      potentials (ERPs) in discriminative reaction task (DRT, Go/No-go task) and simple
      reaction task (SRT) to visual stimuli. In the DRT, in addition to faster RTs
      measured in fencers with respect to control subjects, three main
      electrophysiological differences were found. First, attentional modulation of the
      visual processing taking place in the occipital lobes and reaching a peak at 170
      ms was enhanced in the athletes group. Second, the activity in the posterior
      cingulate gyrus, associated with the stimulus discrimination stage, started
      earlier in fencers than controls (150 ms versus 200 ms) and the peak had larger
      amplitude. Third, the activity at the level of the prefrontal cortex (time range:
      250-350 ms), associated with response selection stage and particularly with motor
      inhibition process, was stronger in fencers. No differences between athletes and
      controls were found in the SRT for both ERPs and RTs. Concluding, the fencers'
      ability to cope to the opponent feint switching quickly from an intended action
      to a new more appropriate action is likely due to a faster stimulus
      discrimination facilitated by higher attention and by stronger inhibition
      activity in prefrontal cortex.

PMID- 17018247
TI  - Capsaicin and nitric oxide synthase inhibitor interact to evoke a hypothermic
      synergy.
AB  - The present study investigated the effect of a drug combination of capsaicin and
      L-NAME on hypothermia in rats. Capsaicin administration (0.1, 0.25, 0.5, 1 and
      2mg/kg, i.m.) caused a significant hypothermia. L-NAME (50mg/kg, i.p.), a
      nonspecific nitric oxide synthase (NOS) inhibitor, was ineffective. For combined
      administration, progressively increasing doses of capsaicin (0.1, 0.25, 0.5, 1
      and 2mg/kg, i.p.) were given with a non-hypothermic dose of L-NAME (50mg/kg,
      i.p.). Experiments revealed that L-NAME (50mg/kg, i.p.) enhanced the hypothermic
      response to capsaicin (0.25, 0.5, 1, and 2mg/kg, i.m.). Comparison of the graded
      dose-effect curves for capsaicin alone and capsaicin plus L-NAME revealed a
      significant difference (P<0.05), thus indicating synergy for the drug
      interaction. To determine if L-NAME acted centrally, a fixed dose of L-NAME
      (1mg/rat, i.c.v.) was given with graded doses of capsaicin (0.25, 0.5, 1, and
      2mg/kg, i.m.). L-NAME (1mg/rat, i.c.v.) only enhanced the hypothermia at a single
      dose of capsaicin (0.5mg/kg, i.m.). The super-additive hypothermia produced by
      the concurrent administration of capsaicin and L-NAME (50mg/kg, i.p.) is the
      first evidence of synergy for a drug combination of capsaicin and a NOS
      inhibitor. The synergy is apparent only when L-NAME is given systemically, thus
      indicating that the inhibition of peripheral NO production enhances the
      hypothermic response to capsaicin.

PMID- 17018248
TI  - Postischemic exercise decreases neurogenesis in the adult rat dentate gyrus.
AB  - Running exercise enhances neurogenesis in the normal adult and aged hippocampus.
      However, the effect of exercise on neurogenesis in the ischemic hippocampus is
      unclear. Here, we show that running exercise has different effects on ischemic
      and non-ischemic brain. Young (3-4-month-old) normotensive Wistar rats were used
      for this study. We administered bromodeoxyuridine (BrdU) to rats 7 days after the
      induction of transient forebrain ischemia or sham operation. BrdU-labeled cells
      were increased in the ischemic subgranular zone (SGZ) and granule cell layer
      (GCL) and double immunofluoresence showed approximately 80% of BrdU-labeled cells
      expressed neuronal markers. To assess the effect of running exercise on
      neurogenesis, BrdU-labeled cells in these regions were quantified after 1 day and
      14 days. In sham-operated rats, the numbers of BrdU-labeled cells were
      significantly increased (2.2-fold) in the SGZ and GCL in response to running
      exercise. The numbers of BrdU-labeled cells were increased in response to
      ischemia, however, they were decreased 14 days after BrdU administration and
      running exercise accelerated the reduction in BrdU-labeled cells in ischemic
      rats. These findings suggest that running exercise has a negative effect on
      neurogenesis in the ischemic hippocampus. This may be important with respect to
      assessment of therapeutic approaches for functional recovery after stroke.

PMID- 17018249
TI  - Hand dominance and multi-finger synergies.
AB  - Recent studies of arm movement reaching to a target have provided support for the
      Dynamic Dominance model of handedness, which proposes that each hemisphere/limb
      system is specialized for controlling different features of performance: The
      dominant system for control of the trajectory, and the nondominant system for
      control of the steady state final position. We now examine a more general form of
      this hypothesis by investigating differences between the right and left hands of
      right-handed persons in their ability to stabilize the combined action of a set
      of fingers. The subjects produced very quick pulses and steps of force from a low
      background force level while pressing with four fingers of one hand. An index of
      force stabilizing synergy showed a strong multi-finger synergy during steady
      state force production followed by a small anticipatory drop in the index prior
      to the force increase. Hand differences emerged during the force increase: The
      left (non-dominant) hand showed a significantly larger drop in the synergy index.
      While our findings support the idea that the dominant system is specialized for
      stabilizing quick changes in performance variables, we failed to support a
      nondominant specialization for stabilizing steady-state isometric force. This may
      be a ceiling effect due to the simplicity of the task for either hand, or it
      might indicate that this aspect of the dynamic dominance hypothesis does not
      generalize to isometric conditions.

PMID- 17018250
TI  - Enhancing security of fingerprints through contextual biometric watermarking.
AB  - This paper presents a novel digital watermarking technique using face and
      demographic text data as multiple watermarks for verifying the chain of custody
      and protecting the integrity of a fingerprint image. The watermarks are embedded
      in selected texture regions of a fingerprint image using discrete wavelet
      transform. Experimental results show that modifications in these locations are
      visually imperceptible and maintain the minutiae details. The integrity of the
      fingerprint image is verified through the high matching scores obtained from an
      automatic fingerprint identification system. There is also a high degree of
      visual correlation between the embedded images, and the extracted images from the
      watermarked fingerprint. The degree of similarity is computed using pixel-based
      metrics and human visual system metrics. The results also show that the proposed
      watermarked fingerprint and the extracted images are resilient to common attacks
      such as compression, filtering, and noise.

PMID- 17018251
TI  - Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph
      node metastasis in oral squamous cell carcinoma: a clinical and histopathological
      analysis of 113 patients.
AB  - The purposes of this study were to examine the correlations between proliferation
      markers and survival rate in oral squamous cell carcinoma (OSCC) patients, and to
      evaluate the efficacy of proliferation markers in predicting lymph node
      metastasis. The patients' age, gender, T score, clinical stage, PCNA and Ki-67
      index were analysed. Univariate analysis showed that T score had a significant
      influence on survival, and stage 4 group had a significantly lower survival rate.
      Lymph node metastasis was also a significant predictor of survival. Using a cut
      off point of 25%, those patients with lower Ki-67 scores had survival advantage
      over those with higher Ki-67 scores. PCNA did not show any differences in
      survival with a cut-off point of 50%. Ki-67 and PCNA were significantly higher in
      the primary tumours associated with lymph node metastasis (pN+) than in those
      without lymph node metastasis (pN0). Multivariate analysis showed that clinical
      stage and Ki-67 were independent prognostic factors for survival in OSCC
      patients. From this result, it can be postulated that the cancer staging based on
      the TNM stage was a powerful prognostic variable and Ki-67 had a significant
      effect on the cumulative survival rate.

PMID- 17018252
TI  - Juvenile ossifying fibroma of the maxilla.
AB  - Juvenile ossifying fibroma is a rare fibro-osseous neoplasm in young children.
      This lesion is locally aggressive and spreads quickly, and because it has a very
      high recurrence rate complete excision is essential. Reported here is a case of a
      massive juvenile ossifying fibroma of the maxilla in an 11-year-old male child. A
      titanium mesh was used to reconstruct the facial contour after a left total
      maxillectomy, achieving a satisfactory facial appearance.

PMID- 17018253
TI  - Polyancora globosa gen. sp. nov., an aeroaquatic fungus from Malaysian peat swamp
      forests.
AB  - During an investigation of submerged leaves and twigs sampled from tropical peat
      swamp forests located in Peninsular Malaysia, an anamorphic fungus not
      attributable to a described genus was detected and isolated in pure culture.
      Conidial ontogeny was thoroughly studied and illustrated using both light and
      SEM, which revealed a unique conidial morphology. Analysis of partial nuLSU rDNA
      and ITS data revealed a phylogenetic position within the Xylariales (Ascomycota),
      but family affiliation remained unclear.

PMID- 17018254
TI  - Glucose-mediated repression of autolysis and conidiogenesis in Emericella
      nidulans.
AB  - Glucose-mediated repression of autolysis and sporulation was studied in submerged
      Emericellanidulans (anam. Aspergillus nidulans) cultures. Null mutation of the
      creA gene, which encodes the major carbon catabolite repressor CreA in E.
      nidulans, resulted in a hyperautolytic phenotype characterized by increased
      extracellular hydrolase production and dry cell mass declination. Interestingly,
      glucose, as well as the glucose antimetabolite 2-deoxy-d-glucose, repressed
      autolysis and sporulation in both the control and the creA null mutant strains
      suggesting that these processes were also subjected to CreA-independent carbon
      regulation. For example, the glucose-mediated, but CreA-independent, repression
      of the sporulation transcription factor BrlA was likely to contribute to the
      negative regulation of conidiogenesis by glucose. Although CreA played a
      prominent role in the regulation of autolysis via the repression of genes
      encoding important autolytic hydrolases like ChiB chitinase and PrtA protease the
      age-related production of the chitinase activity was also negatively affected by
      the down-regulation of brlA expression. However, neither CreA-dependent nor CreA
      independent elements of carbon regulation affected the initiation and regulation
      of cell death in E. nidulans under carbon starvation.

PMID- 17018255
TI  - A new Sparassis species from Spain described using morphological and molecular
      data.
AB  - Sparassis miniensis, collected in Pinus pinaster forests in Galicia (northwest
      Iberian Peninsula) is described as a new species, based on morphological and
      molecular data. Sparassis miniensis is morphologically distinct from all other
      species in the genus Sparassis based on scattered flabellae, which are strongly
      laciniated, azonate, and arise from an orange to rose-purplish base. The sporadic
      presence of clamp connections is restricted to subhymenial hyphae. Molecular data
      from LSU-rDNA, ITS and partial gene coding RNA polymerase subunit II (rpb2)
      suggest a close relationship between the new species S. miniensis and S.
      brevipes, another European species producing large fruiting bodies but with
      entire flabellae and no clamp connections.

PMID- 17018256
TI  - Ovarian cancer.
AB  - Ovarian cancer accounts for 4% of all cancers in women and is the leading cause
      of death from gynaecologic malignancies. Because early-stage ovarian cancer is
      generally asymptomatic, approximately 75% of women present with advanced disease
      at diagnosis. Survival is highly dependent on stage of disease: 5-year survival
      in patients with early-stage is 80-90% compared to 25% for patients with advanced
      stage disease. For all patients, a comprehensive surgical staging should be
      performed to obtain the histological confirmation of diagnosis and to evaluate
      the extent of disease. Patients with early-stage should both be optimally staged
      and be treated with adjuvant platinum-based chemotherapy if they have a medium or
      high-risk tumour. For advanced disease the currently recommended management is
      primary cytoreductive surgery followed by platinum-paclitaxel combination
      chemotherapy. Appropriate salvage therapy is based on the timing and nature of
      recurrence and the extent of prior chemotherapy. Surgical resection should be
      considered in patients with long-term remission, especially in those with
      isolated recurrences and good performance status. Platinum-based combination
      represents the standard second-line chemotherapy in patients with platinum
      sensitive relapsed ovarian cancer. Salvage chemotherapy in platinum-refractory
      patients usually results in low response rates and short survival.

PMID- 17018257
TI  - 3D-QSAR and molecular docking studies on pyrazolopyrimidine derivatives as
      glycogen synthase kinase-3beta inhibitors.
AB  - Glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase, is a fascinating
      enzyme with diverse biological actions in intracellular signaling systems, making
      it an emerging target for diseases such as diabetes mellitus, cancer, chronic
      inflammation, bipolar disorders and Alzheimer's disease. It is important to
      inhibit GSK-3 selectively and the net effect of the GSK-3 inhibitors thus should
      be target specific, over other phylogenetically related kinases such as CDK-2. In
      the present work, we have carried out three-dimensional quantitative structure
      activity relationship (3D-QSAR) studies on novel class of pyrazolopyrimidine
      derivatives as GSK-3 inhibitors reported to have improved cellular activity.
      Docked conformation of the most active molecule in the series, which shows
      desirable interactions in the receptor, was taken as template for alignment of
      the molecules. Statistically significant CoMFA and CoMSIA models were generated
      using 49 molecules in training set. By applying leave-one-out (LOO) cross
      validation study, r(cv)2 values of 0.53 and 0.48 for CoMFA and CoMSIA,
      respectively and non-cross-validated (r(ncv)2) values of 0.98 and 0.92 were
      obtained for CoMFA and CoMSIA models, respectively. The predictive ability of
      CoMFA and CoMSIA models was determined using a test set of 12 molecules which
      gave predictive correlation coefficients (r(pred)2) of 0.47 and 0.48,
      respectively, indicating good predictive power. Based upon the information
      derived from CoMFA and CoMSIA contour maps, we have identified some key features
      that explain the observed variance in the activity and have been used to design
      new pyrazolopyrimidine derivatives. The designed molecules showed better binding
      affinity in terms of estimated docking scores with respect to the already
      reported systems; hence suggesting that newly designed molecules can be more
      potent and selective towards GSK-3beta inhibition.

PMID- 17018258
TI  - Optical biodetection of cadmium and lead ions in water.
AB  - A three layer waveguiding silicon dioxide (SiO(2))/silicon nitride
      (Si(3)N(4))/SiO(2) structure on silicon substrate was proposed as an optically
      efficient biosensor for calibration of heavy metal ions in drinking water. The
      catalytic activities of urease and acetylcholine esterase (AchE) were inhibited
      by the presence of cadmium (Cd(2+)) and lead (Pb(2+)) ions. The detection limit
      as low as 1 ppb was achieved by employing the technique of total reflection at
      the interface between the Si(3)N(4) core and composite polyelectrolyte self
      assembled (PESA) membranes containing cyclotetrachromotropylene (CTCT) as an
      indicator.

PMID- 17018259
TI  - Emodin negatively affects the phosphoinositide 3-kinase/AKT signalling pathway: a
      study on its mechanism of action.
AB  - The development of selective cell-permeable inhibitors of protein kinases whose
      aberrant activation contributes to cell transformation is a promising approach in
      cancer treatment. Emodin is a natural anthraquinone derivative that exhibits anti
      proliferative effects in various cancer cell lines by efficient induction of
      apoptosis. The phosphoinositide 3-kinase (PI3K)/AKT pathway has been shown to be
      central in the promotion of cell survival since the alteration of this signalling
      cascade is a frequent event in human malignancies. Previous published results
      indicated that treatment of cells with inhibitors of protein kinase CK2, such as
      emodin, induces apoptosis and that the anti-apoptotic effect of CK2 is partially
      mediated by target phosphorylation and up-regulation of AKT by CK2. In the
      present study, a screening with selected CK2 inhibitors induced a variable
      response with respect to AKT down-regulation, emodin being the most effective,
      suggesting that other mechanisms other than the inhibition of CK2 were
      responsible for the emodin-mediated modulation of AKT. We found that emodin does
      not directly affect AKT kinase. Furthermore, we show that the down-regulation of
      AKT is due to the emodin-mediated target inhibition of components of the PI3K
      pathway, which directly or indirectly affect AKT activity, i.e. the mammalian
      target of rapamycin and the phosphatase and tensin homolog deleted on chromosome
      10, but not the phosphoinositide-dependent kinase 1. Taken together, our results
      highlight a new mechanism by which emodin exerts anti-cancer activity and suggest
      the further investigation of plant polyphenols, such as emodin, as therapeutic
      and preventive agents for cancer therapy.

PMID- 17018260
TI  - Spectroscopic properties of Nd3+ doped transparent oxyfluoride glass ceramics.
AB  - In this paper, the spectroscopic properties of Nd(3+) doped transparent
      oxyfluoride glass ceramics containing LaF(3) nano-crystals were systematically
      studied. The formation and distribution of LaF(3) nano-crystals in the glass
      matrix were investigated by X-ray diffraction (XRD) and transmission electron
      microscopy (TEM). Based on Judd-Ofelt theory, the intensity parameters Omega(t)
      (t=2, 4, 6), spontaneous emission probability, radiative lifetime, radiative
      quantum efficiency, width of the emission line and stimulated emission cross
      section of Nd(3+) were evaluated. Particularly, the effect of Nd(3+) doping level
      on them was discussed. With the increase of Nd(3+) concentration in the glass
      ceramic, the experimental luminescence lifetime, radiative quantum efficiency and
      stimulated emission cross-section vary from 353.4 micros, 78.3% and 1.86 x 10(
      20)cm(2) to 214.7 micros, 39.9% and 1.52 x 10(-20)cm(2), respectively. The
      comparative study of Nd(3+) spectroscopic parameters in different hosts suggests
      that the investigated glass ceramic system is potentially applicable as laser
      materials for 1.06 microm emission.

PMID- 17018261
TI  - Vibrational spectra and assignments of 2-amino-5-iodopyridine by ab initio
      Hartree-Fock and density functional methods.
AB  - The Fourier transform Raman and Fourier transform infrared spectra of 2-amino-5
      iodopyridine were recorded in the solid phase. The equilibrium geometry, harmonic
      vibrational frequencies, infrared intensities and Raman scattering activities
      were calculated by HF and DFT (B3LYP) methods with the 6-31G(d,p) basis set for
      C, N, H and LANL2DZ pseudopotential for I. The scaled theoretical wavenumbers
      showed very good agreement with the experimental ones. A detailed interpretation
      of the infrared and Raman spectra of 2-amino-5-iodopyridine is reported on the
      basis of the calculated potential energy distribution. The theoretical
      spectrograms for the IR spectrum of the title molecule have been constructed.

PMID- 17018262
TI  - ESR and optical study of Cu2+ doped calcium malonate dihydrate.
AB  - The ESR study of Cu(2+) doped calcium malonate dihydrate has been done at room
      temperature. Four magnetically in-equivalent sites for Cu(2+) have been observed.
      The spin-Hamiltonian parameters evaluated with the fitting of spectra to rhombic
      symmetry crystalline field are for Cu(2+) site (I): g(x)=2.0963+/-0.0002,
      g(y)=2.1316+/-0.0002, g(z)=2.4137+/-0.0002, A(x)=(32+/-2)x10(-4)cm(-1),
      A(y)=(34+/-2)x10(-4)cm(-1), A(z)=(49+/-2)x10(-4)cm(-1), for site (II):
      g(x)=2.0668+/-0.0002, g(y)=2.0800+/-0.0002, g(z)=2.3561+/-0.0002, A(x)=(34+/
      2)x10(-4)cm(-1), A(y)=(36+/-2)x10(-4)cm(-1), A(z)=(51+/-2)x10(-4)cm(-1), for site
      (III): g(x)=2.0438+/-0.0002, g(y)=2.0623+/-0.0002, g(z)=2.2821+/-0.0002,
      A(x)=(34+/-2)x10(-4)cm(-1), A(y)=(36+/-2)x10(-4)cm(-1), A(z)=(53+/-2)x10(-4)cm(
      1), and for site (IV): g(x)=2.0063+/-0.0002, g(y)=2.0241+/-0.0002, g(z)=2.2357+/
      0.0002, A(x)=(35+/-2)x10(-4)cm(-1), A(y)=(37+/-2)x10(-4)cm(-1), A(z)=(54+/-2)x10(
      4)cm(-1). The ground state wave function of Cu(2+) has also been determined. The
      g-anisotropy has been estimated and compared with the experimental value. Further
      with the help of optical study the nature of bonding of metal ion with different
      ligands in the complex has been discussed.

PMID- 17018263
TI  - Modeling a terminology-based electronic nursing record system: an object-oriented
      approach.
AB  - OBJECTIVE: The aim of this study was to present our perspectives on healthcare
      information analysis at a conceptual level and the lessons learned from our
      experience with the development of a terminology-based enterprise electronic
      nursing record system - which was one of components in an EMR system at a
      tertiary teaching hospital in Korea - using an object-oriented system analysis
      and design concept. METHODS: To ensure a systematic approach and effective
      collaboration, the department of nursing constituted a system modeling team
      comprising a project manager, systems analysts, user representatives, an object
      oriented methodology expert, and healthcare informaticists (including the
      authors). A rational unified process (RUP) and the Unified Modeling Language were
      used as a development process and for modeling notation, respectively. RESULTS:
      From the scenario and RUP approach, user requirements were formulated into use
      case sets and the sequence of activities in the scenario was depicted in an
      activity diagram. The structure of the system was presented in a class diagram.
      CONCLUSION: This approach allowed us to identify clearly the structural and
      behavioral states and important factors of a terminology-based ENR system (e.g.,
      business concerns and system design concerns) according to the viewpoints of both
      domain and technical experts.

PMID- 17018264
TI  - Profound hypoxaemia corrected by PFO closure device in carcinoid heart disease.
AB  - A 66-year-old man with known metastatic carcinoid tumor presented with increasing
      dyspnoea, right heart failure and marked hypoxaemia which did not correct with
      oxygen. Echocardiography demonstrated severe tricuspid regurgitation, moderate
      pulmonary regurgitation and marked right heart dilatation. The inter-atrial
      septum was aneurysmal, with a large patent foramen ovale (PFO) with continuous
      right to left shunting. Cardiac catheterization demonstrated oxygen saturations
      of 96% in the pulmonary veins and 74% in the left atrium with a significant right
      to left shunt. During percutaneous closure of the PFO, anaesthetic induction
      resulted in marked systemic hypotension and worsening hypoxia related to systemic
      vasodilatation and increased shunting. PFO flow was temporarily obstructed with a
      sizing balloon resulting in a rapid increase in arterial oxygen saturation from
      60% to >90%, but marked systemic hypotension due to acute left ventricular
      preload reduction, requiring volume replacement and adrenaline. Following
      deployment of a PFO occluder device, prominent pulsatile splaying of the right
      and left discs was noted due to the severe tricuspid regurgitation, resulting in
      some residual inter-atrial shunting. Arterial oxygen saturation was 83%,
      increasing to 92% at day 4 post-procedure as tissue organization occurred within
      the device, and the patient reported improvement in dyspnoea.

PMID- 17018265
TI  - Slow base excision by human alkyladenine DNA glycosylase limits the rate of
      formation of AP sites and AP endonuclease 1 does not stimulate base excision.
AB  - The base excision repair pathway removes damaged DNA bases and resynthesizes DNA
      to replace the damage. Human alkyladenine DNA glycosylase (AAG) is one of several
      damage-specific DNA glycosylases that recognizes and excises damaged DNA bases.
      AAG removes primarily damaged adenine residues. Human AP endonuclease 1 (APE1)
      recognizes AP sites produced by DNA glycosylases and incises the phophodiester
      bond 5' to the damaged site. The repair process is completed by a DNA polymerase
      and DNA ligase. If not tightly coordinated, base excision repair could generate
      intermediates that are more deleterious to the cell than the initial DNA damage.
      The kinetics of AAG-catalyzed excision of two damaged bases, hypoxanthine and
      1,N6-ethenoadenine, were measured in the presence and absence of APE1 to
      investigate the mechanism by which the base excision activity of AAG is
      coordinated with the AP incision activity of APE1. 1,N6-ethenoadenine is excised
      significantly slower than hypoxanthine and the rate of excision is not affected
      by APE1. The excision of hypoxanthine is inhibited to a small degree by
      accumulated product, and APE1 stimulates multiple turnovers by alleviating
      product inhibition. These results show that APE1 does not significantly affect
      the kinetics of base excision by AAG. It is likely that slow excision by AAG
      limits the rate of AP site formation in vivo such that AP sites are not created
      faster than can be processed by APE1.

PMID- 17018266
TI  - Ventilatory roll off during sustained hypercapnia is gender specific in pekin
      ducks.
AB  - The objective of the present study was to examine the relative roles of
      peripheral versus central mechanisms in producing ventilatory adjustments in
      pekin ducks during prolonged (5 h) hypercapnia (5% inspired CO2), and to
      determine whether these adjustments differed between male and female ducks. After
      20 min of CO2 exposure, intact ducks increased total ventilation (VE) 2.5-3-fold
      above control values, due to large increases (approximately 200%) in tidal volume
      (VT) and slightly smaller increases (approximately 140%) in breathing frequency
      (fR). This response was accompanied by respiratory acidosis (pHa fell from
      approximately 7.46 to approximately 7.41) and hypercapnia (PaCO2 increased from
      approximately 35 to approximately 40 Torr). In males, VE fell progressively
      thereafter due exclusively to a fall in fR, in parallel with a rapid partial
      recovery of pH (to 7.44) while PaCO2 continued to climb (to approximately 42
      Torr). In females, VE remained elevated during hypercapnia, and no pH recovery
      occurred. This suggests that a respiratory decline resulting from acid-base
      compensation (probably due to HCO3- mobilization) occurred in males but not in
      females. Bicarbonate mobilization, and thus pH compensation, may have been
      reduced in females due to the CaCO3 requirements of eggshell formation. In males,
      the acute ventilatory response was reduced slightly by denervation of the carotid
      bodies or intrapulmonary chemoreceptors, but there was no effect of denervation
      of either receptor group on the responses to prolonged CO2. We conclude that pH
      compensation triggered by constant or increasing PaCO2, acting at central
      chemoreceptors, likely mediates the respiratory adjustments seen in male pekin
      ducks during hypercapnia. Furthermore, we suggest that this ventilatory response
      be considered a gender-specific hypercapnic ventilatory roll off, in the context
      of the various time domains of the hypercapnic ventilatory response.

PMID- 17018267
TI  - Inspiratory muscles experience fatigue faster than the calf muscles during
      treadmill marching.
AB  - The possibility that respiratory muscles may fatigue during extreme physical
      activity and thereby become a limiting factor leading to exhaustion is debated in
      the literature. The aim of this study was to determine whether treadmill marching
      exercise induces respiratory muscle fatigue, and to compare the extent and rate
      of respiratory muscle fatigue to those of the calf musculature. To identify
      muscle fatigue, surface electromyographic (EMG) signals of the inspiratory
      (sternomastoid, external intercostals), expiratory (rectus abdominis and external
      oblique) and calf (gastrocnemius lateralis) muscles were measured during a
      treadmill march of 2 km at a constant velocity of 8 km/h. The extent of fatigue
      was assessed by determining the increase in root-mean-square (RMS) of EMG over
      time, and the rate of fatigue was assessed from the slope of the EMG RMS versus
      time curve. Results indicated that (i) the inspiratory and calf muscles are the
      ones experiencing the most dominant fatigue during treadmill marching, (ii) the
      rate of fatigue of each muscle group was monotonic between the initial and
      terminal phases of exercise, and (iii) the inspiratory muscles fatigue
      significantly faster than the calf at the terminal phase of exercise, and are
      likely to fatigue faster during the initial exercise as well. Accordingly, this
      study supports the hypothesis that fatigue of the inspiratory muscles may be a
      limiting factor during exercise.

PMID- 17018268
TI  - Development of neonatal EEG activity: from phenomenology to physiology.
AB  - After having been in routine use for about half a century, neonatal EEG is
      currently facing unprecedented challenges in assessing and monitoring brain
      function during intensive care of preterm babies. It has therefore become
      increasingly important to understand the neurophysiological processes underlying
      EEG activity, as well as to identify those features of brain activity that are
      essential for brain development. By integrating the existing literature from
      basic neuroscience to neonatal EEG, the present review proposes a simple,
      neurophysiologically and neuroanatomically based framework for neonatal EEG
      interpretation. This is composed of two developmental trajectories: one related
      to discrete spontaneous activity transients (SAT) and the other to the ongoing,
      apparently oscillatory EEG activity. This framework can readily be applied to
      clinical use. It may open novel avenues to automated analysis in EEG monitoring
      and, moreover, it may facilitate genuine translational research.

PMID- 17018269
TI  - Indian science in transition.
AB  - India is a country in transition, and so is its science. Scientific institutions,
      researchers, regulatory agencies, and government policies are in a state of flux
      as changes are instigated to overcome the bureaucracy and inertia that are
      characteristic of a populous developing nation.

PMID- 17018270
TI  - The key to left-right asymmetry.
AB  - Establishment of left-right asymmetry in vertebrates involves cilia as essential
      components in the breaking of symmetry, an asymmetric signaling cascade, and a
      midline barrier that helps to maintain asymmetry. A new study suggests that a
      reaction-diffusion mechanism also plays a key role.

PMID- 17018271
TI  - Cargo takes control of endocytosis.
AB  - Clathrin-mediated endocytosis is a major route for diverse cargo to enter the
      cellular endocytic pathway. New findings by Puthenveedu and von Zastrow (2006)
      suggest that certain cargo proteins, such as G protein coupled receptors that
      bind to PDZ domains, regulate their own targeting to a subset of clathrin-coated
      pits. Thus, cargo proteins may cause functional specialization of vesicle
      trafficking within the early endocytic pathway.

PMID- 17018272
TI  - Driving actin dynamics under the influence of alcohol.
AB  - The actin cytoskeleton plays a pivotal role in regulating neuronal development
      and activity, and dysregulation of actin dynamics has been linked to impaired
      cognitive function. In this issue of Cell Rothenfluh et al. (2006) , and
      Offenhauser et al. (2006) show that actin dynamics can also affect the cellular
      and behavioral responses of flies and mice to alcohol.

PMID- 17018273
TI  - Unwinding a path to nuclear beta-catenin.
AB  - In this issue of Cell, Yang et al. (2006b) show that PDGF, a growth factor that
      induces the transition of epithelial cells to mesenchymal cells, stimulates the c
      Abl kinase-dependent phosphorylation of p68 RNA helicase. Phosphorylated p68
      dissociates beta-catenin from the Axin destruction complex, thereby promoting
      nuclear beta-catenin signaling independent of Wnt activation.

PMID- 17018274
TI  - RalB signaling: a bridge between inflammation and cancer.
AB  - A connection between the genetic events that lead to tumor formation and the
      signaling pathways of the innate immune response has been established. In this
      issue, Chien et al. (2006) show that the RalB GTPase regulates the IKK family
      member TBK1, providing an unexpected link between the signaling pathways that
      promote inflammation and cancer. In tumor cells the RalB/TBK1 pathway inhibits
      apoptosis and in nontumorigenic cells it stimulates an innate immune response.

PMID- 17018275
TI  - Nuclear signaling by receptor tyrosine kinases: the first robin of spring.
AB  - The role of receptor tyrosine kinases (RTKs) in transmembrane signaling is well
      established. Recently, ligand-dependent translocation of RTKs to the nucleus has
      been reported, but the functional importance of this process remains unclear. In
      this issue, Sardi et al. (2006) provide evidence for direct signaling in the
      nucleus by an intracellular ErbB4 receptor fragment that is released upon
      receptor activation by ligand. The fragment forms a complex with the adaptor TAB2
      and the corepressor N-CoR and transits to the nucleus, where it represses
      transcription of genes that promote the formation of astrocytes.

PMID- 17018276
TI  - Dendritic protein synthesis, synaptic plasticity, and memory.
AB  - Considerable evidence suggests that the formation of long-term memories requires
      a critical period of new protein synthesis. Recently, the notion that some of
      these newly synthesized proteins originate through local translation in neuronal
      dendrites has gained some traction. Here, we review the experimental support for
      this idea and highlight some of the key questions outstanding in this area.

PMID- 17018277
TI  - Transcriptional repression of PGC-1alpha by mutant huntingtin leads to
      mitochondrial dysfunction and neurodegeneration.
AB  - Huntington's disease (HD) is an inherited neurodegenerative disease caused by a
      glutamine repeat expansion in huntingtin protein. Transcriptional deregulation
      and altered energy metabolism have been implicated in HD pathogenesis. We report
      here that mutant huntingtin causes disruption of mitochondrial function by
      inhibiting expression of PGC-1alpha, a transcriptional coactivator that regulates
      several metabolic processes, including mitochondrial biogenesis and respiration.
      Mutant huntingtin represses PGC-1alpha gene transcription by associating with the
      promoter and interfering with the CREB/TAF4-dependent transcriptional pathway
      critical for the regulation of PGC-1alpha gene expression. Crossbreeding of PGC
      1alpha knockout (KO) mice with HD knockin (KI) mice leads to increased
      neurodegeneration of striatal neurons and motor abnormalities in the HD mice.
      Importantly, expression of PGC-1alpha partially reverses the toxic effects of
      mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated
      delivery of PGC-1alpha in the striatum provides neuroprotection in the transgenic
      HD mice. These studies suggest a key role for PGC-1alpha in the control of energy
      metabolism in the early stages of HD pathogenesis.

PMID- 17018278
TI  - RNA ligase structures reveal the basis for RNA specificity and conformational
      changes that drive ligation forward.
AB  - T4 RNA ligase 2 (Rnl2) and kinetoplastid RNA editing ligases exemplify a family
      of RNA repair enzymes that seal 3'OH/5'PO(4) nicks in duplex RNAs via ligase
      adenylylation (step 1), AMP transfer to the nick 5'PO(4) (step 2), and attack by
      the nick 3'OH on the 5'-adenylylated strand to form a phosphodiester (step 3).
      Crystal structures are reported for Rnl2 at discrete steps along this pathway:
      the covalent Rnl2-AMP intermediate; Rnl2 bound to an adenylylated nicked duplex,
      captured immediately following step 2; and Rnl2 at an adenylylated nick in a
      state poised for step 3. These structures illuminate the stereochemistry of
      nucleotidyl transfer and reveal how remodeling of active-site contacts and
      conformational changes propel the ligation reaction forward. Mutational analysis
      and comparison of nick-bound structures of Rnl2 and human DNA ligase I highlight
      common and divergent themes of substrate recognition that can explain their
      specialization for RNA versus DNA repair.

PMID- 17018279
TI  - Measurement of conformational changes accompanying desensitization in an
      ionotropic glutamate receptor.
AB  - The canonical conformational states occupied by most ligand-gated ion channels,
      and many cell-surface receptors, are the resting, activated, and desensitized
      states. While the resting and activated states of multiple receptors are well
      characterized, elaboration of the structural properties of the desensitized
      state, a state that is by definition inactive, has proven difficult. Here we use
      electrical, chemical, and crystallographic experiments on the AMPA-sensitive
      GluR2 receptor, defining the conformational rearrangements of the agonist binding
      cores that occur upon desensitization of this ligand-gated ion channel. These
      studies demonstrate that desensitization involves the rupture of an extensive
      interface between domain 1 of 2-fold related glutamate-binding core subunits,
      compensating for the ca. 21 degrees of domain closure induced by glutamate
      binding. The rupture of the domain 1 interface allows the ion channel to close
      and thereby provides a simple explanation to the long-standing question of how
      agonist binding is decoupled from ion channel gating upon receptor
      desensitization.

PMID- 17018280
TI  - Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal
      degradation.
AB  - Ubiquitin chains serve as a recognition motif for the proteasome, a multisubunit
      protease, which degrades its substrates into polypeptides while releasing
      ubiquitin for reuse. Yeast proteasomes contain two deubiquitinating enzymes, Ubp6
      and Rpn11. Rpn11 promotes protein breakdown through its degradation-coupled
      activity. In contrast, we show here that Ubp6 has the capacity to delay the
      degradation of ubiquitinated proteins by the proteasome. However, delay of
      degradation by Ubp6 does not require its catalytic activity, indicating that Ubp6
      has both deubiquitinating activity and proteasome-inhibitory activity. Delay of
      degradation by Ubp6 appears to provide a time window allowing gradual
      deubiquitination of the substrate by Ubp6. Rpn11 catalyzes en bloc chain removal,
      and Ubp6 interferes with degradation at or upstream of this step, so that
      degradation delay by Ubp6 is accompanied by a switch in the mode of ubiquitin
      chain processing. We propose that Ubp6 regulates both the nature and magnitude of
      proteasome activity.

PMID- 17018281
TI  - Cargo regulates clathrin-coated pit dynamics.
AB  - Clathrin-coated pits (CCPs) are generally considered a uniform population of
      endocytic machines containing mixed constitutive and regulated membrane cargo.
      Contrary to this view, we show that regulated endocytosis of G protein-coupled
      receptors (GPCRs) occurs preferentially through a subset of CCPs. Significantly,
      GPCR-containing CCPs are also functionally distinct, as their surface residence
      time is regulated locally by GPCR cargo via PDZ-dependent linkage to the actin
      cytoskeleton. Such cargo-regulated CCPs show delayed recruitment of dynamin and
      can undergo an abortive event in which clathrin coats separate from the plasma
      membrane without concomitant receptor endocytosis. Segregation of cargo into CCP
      subsets, combined with cargo-dependent control of CCP dynamics, suggests a simple
      kinetic mechanism to generate functional specialization early in the endocytic
      pathway and reduce competition between diverse endocytic cargo.

PMID- 17018282
TI  - P68 RNA helicase mediates PDGF-induced epithelial mesenchymal transition by
      displacing Axin from beta-catenin.
AB  - The nuclear p68 RNA helicase (referred to as p68) is a prototypical member of the
      DEAD box family of RNA helicases. The protein plays a very important role in
      early organ development. In the present study, we characterized the tyrosine
      phosphorylation of p68 under platelet-derived growth factor (PDGF) stimulation.
      We demonstrated that tyrosine phosphorylation of p68 at Y593 mediated PDGF
      stimulated epithelial-mesenchymal transition (EMT). We showed that PDGF treatment
      led to phosphorylation of p68 at Y593 in the cell nucleus. The Y593
      phosphorylated p68 (referred to as phosphor-p68) promotes beta-catenin nuclear
      translocation via a Wnt-independent pathway. The phosphor-p68 facilitates beta
      catenin nuclear translocation by blocking phosphorylation of beta-catenin by GSK
      3beta and displacing Axin from beta-catenin. The beta-catenin nuclear
      translocation and subsequent interaction with the LEF/TCF was required for the
      EMT process. These data demonstrated a novel mechanism of phosphor-p68 in
      mediating the growth factor-induced EMT and uncovered a new pathway to promote
      beta-catenin nuclear translocation.

PMID- 17018283
TI  - RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate
      immune signaling to tumor cell survival.
AB  - The monomeric RalGTPases, RalA and RalB are recognized as components of a
      regulatory framework supporting tumorigenic transformation. Specifically, RalB is
      required to suppress apoptotic checkpoint activation, the mechanistic basis of
      which is unknown. Reported effector proteins of RalB include the Sec5 component
      of the exocyst, an octameric protein complex implicated in tethering of vesicles
      to membranes. Surprisingly, we find that the RalB/Sec5 effector complex directly
      recruits and activates the atypical IkappaB kinase family member TBK1. In cancer
      cells, constitutive engagement of this pathway, via chronic RalB activation,
      restricts initiation of apoptotic programs typically engaged in the context of
      oncogenic stress. Although dispensable for survival in a nontumorigenic context,
      this pathway helps mount an innate immune response to virus exposure. These
      observations define the mechanistic contribution of RalGTPases to cancer cell
      survival and reveal the RalB/Sec5 effector complex as a component of TBK1
      dependent innate immune signaling.

PMID- 17018284
TI  - Tcf3 governs stem cell features and represses cell fate determination in skin.
AB  - Many stem cells (SCs) respond to Wnt signaling, but whether beta-catenin's DNA
      binding partners, the Tcfs, play a role in SCs in the absence of Wnts, is
      unknown. In adult skin, quiescent multipotent progenitors express Tcf3 and commit
      to a hair cell fate in response to Wnt signaling. We find that embryonic skin
      progenitors also express Tcf3. Using an inducible system in mice, we show that
      upon Tcf3 reactivation, committed epidermal cells induce genes associated with an
      undifferentiated, Wnt-inhibited state and Tcf3 promotes a transcriptional program
      shared by embryonic and postnatal SCs. Further, Tcf3-repressed genes include
      transcriptional regulators of the epidermal, sebaceous gland and hair follicle
      differentiation programs, and correspondingly, all three terminal differentiation
      pathways are suppressed when Tcf3 is induced postnatally. These data suggest that
      in the absence of Wnt signals, Tcf3 may function in skin SCs to maintain an
      undifferentiated state and, through Wnt signaling, directs these cells along the
      hair lineage.

PMID- 17018285
TI  - Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis
      in the developing brain.
AB  - Embryonic multipotent neural precursors are exposed to extracellular signals
      instructing them to adopt different fates, neuronal or glial. However, the
      mechanisms by which precursors integrate these signals to make timely fate
      choices remained undefined. Here we show that direct nuclear signaling by a
      receptor tyrosine kinase inhibits the responses of precursors to astrocyte
      differentiation factors while maintaining their neurogenic potential. Upon
      neuregulin-induced activation and presenilin-dependent cleavage of ErbB4, the
      receptor's intracellular domain forms a complex with TAB2 and the corepressor N
      CoR. This complex undergoes nuclear translocation and binds promoters of
      astrocytic genes, repressing their expression. Consistent with this observation,
      astrogenesis occurs precociously in ErbB4 knockout mice. Our studies define how
      presenilin-dependent nuclear signaling by a receptor tyrosine kinase directly
      regulates gene transcription and cell fate. This pathway could be of importance
      for neural stem cell biology and for understanding the pathogenesis of
      Alzheimer's disease.

PMID- 17018286
TI  - Distinct behavioral responses to ethanol are regulated by alternate RhoGAP18B
      isoforms.
AB  - In most organisms, low ethanol doses induce increased activity, while high doses
      are sedating. To investigate the underlying mechanisms, we isolated Drosophila
      mutants with altered ethanol responsiveness. Mutations in white rabbit (whir),
      disrupting RhoGAP18B, are strongly resistant to the sedating effects of ethanol.
      This resistance can be suppressed by reducing the levels of Rho1 or Rac,
      implicating these GTPases in the behavioral response to ethanol. Indeed,
      expression of constitutively active forms of Rho1 or Rac1 in adult flies results
      in ethanol resistance similar to that observed in whir mutants. The whir locus
      produces several transcripts, RA-RD, which are predicted to encode three distinct
      RhoGAPs that share only the GAP domain. The RC transcript mediates the sedating
      effects of ethanol, while the RA transcript regulates its stimulant effects.
      Thus, distinct RhoGAPs, encoded by the same gene, regulate different
      manifestations of acute ethanol intoxication.

PMID- 17018287
TI  - Increased ethanol resistance and consumption in Eps8 knockout mice correlates
      with altered actin dynamics.
AB  - Dynamic modulation of the actin cytoskeleton is critical for synaptic plasticity,
      abnormalities of which are thought to contribute to mental illness and addiction.
      Here we report that mice lacking Eps8, a regulator of actin dynamics, are
      resistant to some acute intoxicating effects of ethanol and show increased
      ethanol consumption. In the brain, the N-methyl-D-aspartate (NMDA) receptor is a
      major target of ethanol. We show that Eps8 is localized to postsynaptic
      structures and is part of the NMDA receptor complex. Moreover, in Eps8 null mice,
      NMDA receptor currents and their sensitivity to inhibition by ethanol are
      abnormal. In addition, Eps8 null neurons are resistant to the actin-remodeling
      activities of NMDA and ethanol. We propose that proper regulation of the actin
      cytoskeleton is a key determinant of cellular and behavioral responses to
      ethanol.

PMID- 17018288
TI  - Rheostat control of gene expression by metabolites.
AB  - Organisms adapt to changes in environmental conditions by altering gene
      expression. Such homeostatic control is apparent in metabolism, where
      biosynthetic metabolites play a role in regulatory feedback loops. Increasing
      evidence shows that small-molecule metabolites also shape the structure of
      chromatin and directly regulate the transcription and translation processes.
      These endogenous metabolites bind specialized histones, are used as substrates by
      chromatin-modifying enzymes, regulate the activity of transcriptional
      corepressors, and even modulate the structure of RNA itself. In doing so, they
      act as dynamic rheostats that fine-tune the activity of hard-wired gene circuits.
      Metabolites emerge as key effectors in tweaking gene expression.

PMID- 17018289
TI  - Mechanism of actin filament turnover by severing and nucleation at different
      concentrations of ADF/cofilin.
AB  - ADF/cofilins are key regulators of actin dynamics during cellular motility, yet
      their precise role and mechanism of action are shrouded in ambiguity. Direct
      observation of actin filaments by evanescent wave microscopy showed that cofilins
      from fission yeast and human do not increase the rate that pointed ends of actin
      filaments shorten beyond the rate for ADP-actin subunits, but both cofilins
      inhibit elongation and subunit dissociation at barbed ends. Direct observation
      also showed that cofilins from fission yeast, Acanthamoeba, and human sever actin
      filaments optimally at low-cofilin binding densities well below their K(d)s, but
      not at high binding densities. High concentrations of cofilin nucleate actin
      assembly. Thus, the action of cofilins in cells will depend on the local
      concentration of active cofilins: low concentrations favor severing, whereas high
      concentrations favor nucleation. These results establish a clear paradigm for
      actin turnover by cofilin in cells.

PMID- 17018290
TI  - Identification of the TRiC/CCT substrate binding sites uncovers the function of
      subunit diversity in eukaryotic chaperonins.
AB  - The ring-shaped hetero-oligomeric chaperonin TRiC/CCT uses ATP to fold a diverse
      subset of eukaryotic proteins. To define the basis of TRiC/CCT substrate
      recognition, we mapped the chaperonin interactions with the VHL tumor suppressor.
      VHL has two well-defined TRiC binding determinants. Each determinant contacts a
      specific subset of chaperonin subunits, indicating that TRiC paralogs exhibit
      distinct but overlapping specificities. The substrate binding site in these
      subunits localizes to a helical region in the apical domains that is structurally
      equivalent to that of bacterial chaperonins. Transferring the distal portion of
      helix 11 between TRiC subunits suffices to transfer specificity for a given
      substrate motif. We conclude that the architecture of the substrate binding
      domain is evolutionarily conserved among eukaryotic and bacterial chaperonins.
      The unique combination of specificity and plasticity in TRiC substrate binding
      may diversify the range of motifs recognized by this chaperonin and contribute to
      its unique ability to fold eukaryotic proteins.

PMID- 17018292
TI  - Distinct structural and functional properties of the ATPase sites in an
      asymmetric ABC transporter.
AB  - The ABC transporter associated with antigen processing (TAP) shuttles cytosolic
      peptides into the endoplasmic reticulum for loading onto class I MHC molecules.
      Transport is fueled by ATP binding and hydrolysis at two distinct cytosolic
      ATPase sites. One site comprises consensus motifs shared among most ABC
      transporters, while the second has substituted, degenerate motifs. Biochemical
      and crystallography experiments with a TAP cytosolic domain demonstrate that the
      consensus ATPase site has high catalytic activity and facilitates ATP-dependent
      dimerization of the cytosolic domains, which is an important conformational
      change during transport. In contrast, the degenerate site is defective in
      dimerization and ATP hydrolysis. Full-length TAP mutagenesis demonstrates the
      necessity for at least one consensus site, supporting our conclusion that the
      consensus site is the principal facilitator of substrate transport. Since
      asymmetry of the ATPase site motifs is a feature of many mammalian homologs, our
      proposed model has broad implications for ABC transporters.

PMID- 17018291
TI  - ATP binding and ATP hydrolysis play distinct roles in the function of 26S
      proteasome.
AB  - The 26S proteasome degrades polyubiquitinated proteins by an energy-dependent
      mechanism. Here we define multiple roles for ATP in 26S proteasome function. ATP
      binding is necessary and sufficient for assembly of 26S proteasome from 20S
      proteasome and PA700/19S subcomplexes and for proteasome activation. Proteasome
      assembly and activation may require distinct ATP binding events. The 26S
      proteasome degrades nonubiquitylated, unstructured proteins without ATP
      hydrolysis, indicating that substrate translocation per se does not require the
      energy of hydrolysis. Nonubiquitylated folded proteins and certain
      polyubiquitylated folded proteins were refractory to proteolysis. The latter were
      deubiquitylated by an ATP-independent mechanism. Other folded as well as
      unstructured polyubiquitylated proteins required ATP hydrolysis for proteolysis
      and deubiquitylation. Thus, ATP hydrolysis is not used solely for substrate
      unfolding. These results indicate that 26S proteasome-catalyzed degradation of
      polyubiquitylated proteins involves mechanistic coupling of several processes and
      that such coupling imposes an energy requirement not apparent for any isolated
      process.

PMID- 17018293
TI  - Spatiotemporal regulation of c-Fos by ERK5 and the E3 ubiquitin ligase UBR1, and
      its biological role.
AB  - c-Fos is regulated by phosphorylation and multiple turnover mechanisms. We found
      that c-Fos was ubiquitylated in the cytoplasm during IL-6/gp130 stimulation under
      MEK inhibition and sought the mechanisms involved in the regulation. We show that
      sustained ERK5 activity and the E3 ligase UBR1 regulate the stability and
      subcellular localization of c-Fos. UBR1, rapidly induced by STAT3, interacts with
      and ubiquitylates c-Fos in the cytoplasm for its accelerated degradation. ERK5
      inhibits the nuclear export of c-Fos by phosphorylating Thr232 in the c-Fos
      NES(221-233) and disrupts the interaction of c-Fos with UBR1 by phosphorylating
      Ser32. Moreover, UBR1 depletion in HeLa cells, which constitutively express UBR1
      at a high level, enhances both c-Fos expression and cell growth, whereas ERK5
      depletion reduces both of them. Interestingly, an NES mutant of c-Fos, but not
      wild-type, substitutes ERK5 activity for HeLa cell proliferation. Thus, this
      spatiotemporal regulation of c-Fos by ERK5 and UBR1 is critical for the
      regulation of c-Fos/AP-1.

PMID- 17018294
TI  - Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate
      protein HIPK2.
AB  - Sumoylation serves to control key cellular functions, but the regulation of SUMO
      E3 ligase activity is largely unknown. Here we show that the polycomb group
      protein Pc2 binds to and colocalizes with homeodomain interacting protein kinase
      2 (HIPK2) and serves as a SUMO E3 ligase for this kinase. DNA damage-induced
      HIPK2 directly phosphorylates Pc2 at multiple sites, which in turn controls Pc2
      sumoylation and intranuclear localization. Inducible phosphorylation of Pc2 at
      threonine 495 is required for its ability to increase HIPK2 sumoylation in
      response to DNA damage, thereby establishing an autoregulatory feedback loop
      between a SUMO substrate and its cognate E3 ligase. Sumoylation enhances the
      ability of HIPK2 to mediate transcriptional repression, thus providing a
      mechanistic link for DNA damage-induced transcriptional silencing.

PMID- 17018295
TI  - Architecture of a polycomb nucleoprotein complex.
AB  - Polycomb group (PcG) epigenetic silencing proteins act through cis-acting DNA
      sequences, named Polycomb response elements (PREs). Within PREs, Pleiohomeotic
      (PHO) binding sites and juxtaposed Pc binding elements (PBEs) function as an
      integrated DNA platform for the synergistic binding of PHO and the multisubunit
      Polycomb core complex (PCC). Here, we analyzed the architecture of the
      PHO/PCC/PRE nucleoprotein complex. DNase I footprinting revealed extensive
      contacts between PHO/PCC and the PRE. Scanning force microscopy (SFM) in
      combination with DNA topological assays suggested that PHO/PCC wraps the PRE DNA
      around its surface in a constrained negative supercoil. These features are
      difficult to reconcile with the simultaneous presence of nucleosomes at the PRE.
      Indeed, chromatin immunoprecipitations (ChIPs) and nuclease mapping demonstrated
      that PREs are nucleosome depleted in vivo. We discuss the implications of these
      findings for models explaining PRE function.

PMID- 17018296
TI  - Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to
      promote S phase progression.
AB  - Origins of DNA replication are licensed in G1 by recruiting the minichromosome
      maintenance (MCM) proteins to form a prereplicative complex (pre-RC). Prior to
      initiation of DNA synthesis from each origin, a preinitiation complex (pre-IC)
      containing Cdc45 and other proteins is formed. We report that Cdc7-Dbf4 protein
      kinase (DDK) promotes assembly of a stable Cdc45-MCM complex exclusively on
      chromatin in S phase. In this complex, Mcm4 is hyperphosphorylated. Studies in
      vitro using purified DDK and Mcm4 demonstrate that hyperphosphorylation occurs at
      the Mcm4 N terminus. However, the DDK substrate specificity is conferred by an
      adjacent DDK-docking domain (DDD), sufficient for facilitating efficient
      phosphorylation of artificial phosphoacceptors in cis. Genetic evidence suggests
      that phosphorylation of Mcm4 by DDK is important for timely S phase progression
      and for cell viability upon overproduction of Cdc45. We suggest that DDK docks on
      and phosphorylates MCM proteins at licensed origins to promote proper assembly of
      pre-IC.

PMID- 17018298
TI  - DNA degradation at unprotected telomeres in yeast is regulated by the CDK1
      (Cdc28/Clb) cell-cycle kinase.
AB  - In the absence of functional telomeric cap protection, the ends of eukaryotic
      chromosomes are subject to DNA damage responses that lead to cell-cycle arrest
      and, eventually, genomic instability. However, the controlling activities
      responsible for the initiation of genome instability on unprotected telomeres
      remained unclear. Here we show that in budding yeast, unprotected telomeres
      undergo a tightly cell-cycle-regulated DNA degradation. Ablation of the function
      of essential capping proteins Cdc13p or Stn1p only caused telomere degradation in
      G2/M, but not in G1 of the cell cycle. Accordingly, G1-arrested cells with
      unprotected telomeres remained viable, while G2/M-arrested cells failed to
      recover. The data also show that completion of S phase and the activity of the S
      Cdk1 kinase were required for telomere degradation. These results strongly
      suggest that after a loss of the telomere capping function, telomere-led genome
      instability is caused by tightly regulated cellular DNA repair attempts.

PMID- 17018297
TI  - Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA
      damage.
AB  - Base excision repair (BER) plays an essential role in protecting cells from
      mutagenic base damage caused by oxidative stress, hydrolysis, and environmental
      factors. POLQ is a DNA polymerase, which appears to be involved in translesion
      DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308
      and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double
      mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to
      oxidative base damage induced by H(2)O(2), but not to UV or cisplatin.
      Surprisingly, this phenotype was synergistically increased by concomitant
      deletion of the major BER polymerase, POLbeta. Moreover, extracts from a polq
      null mutant cell line show reduced BER activity, and POLQ, like POLbeta,
      accumulated rapidly at sites of base damage. Accordingly, POLQ and POLbeta share
      an overlapping function in the repair of oxidative base damage. Taken together,
      these results suggest a role for vertebrate POLQ in BER.

PMID- 17018299
TI  - Elevated levels of two tRNA species bypass the requirement for elongator complex
      in transcription and exocytosis.
AB  - The Saccharomyces cerevisiae Elongator complex consisting of the six Elp1-Elp6
      proteins has been proposed to participate in three distinct cellular processes:
      transcriptional elongation, polarized exocytosis, and formation of modified
      wobble uridines in tRNA. Therefore it was important to clarify whether Elongator
      has three distinct functions or whether it regulates one key process that leads
      to multiple downstream effects. Here, we show that the phenotypes of Elongator
      deficient cells linking the complex to transcription and exocytosis are
      suppressed by increased expression of two tRNA species. Elongator is required for
      formation of the mcm(5) group of the modified wobble nucleoside 5
      methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U) in these tRNAs. Hence, in cells
      with normal levels of these tRNAs, presence of mcm(5)s(2)U is crucial for
      posttranscriptional expression of gene products important in transcription and
      exocytosis. Our results indicate that the physiologically relevant function of
      the evolutionary-conserved Elongator complex is in formation of modified
      nucleosides in tRNAs.

PMID- 17018300
TI  - MicroRNA pathways modulate polyglutamine-induced neurodegeneration.
AB  - Nine human neurodegenerative diseases are due to expansion of a CAG repeat-
      encoding glutamine within the open reading frame of the respective genes.
      Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal
      degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell
      death during development. To address whether miRNA pathways play a role in
      neurodegeneration, we tested whether genes critical for miRNA processing
      modulated toxicity induced by the spinocerebellar ataxia type 3 (SCA3) protein.
      These studies revealed a striking enhancement of polyQ toxicity upon reduction of
      miRNA processing in Drosophila and human cells. In parallel genetic screens, we
      identified the miRNA bantam (ban) as a potent modulator of both polyQ and tau
      toxicity in flies. Our studies suggest that ban functions downstream of toxicity
      of the SCA3 protein, to prevent degeneration. These findings indicate that miRNA
      pathways dramatically modulate polyQ- and tau-induced neurodegeneration,
      providing the foundation for new insight into therapeutics.

PMID- 17018301
TI  - Is there a causal relation between the administration of gadolinium based
      contrast media and the development of nephrogenic systemic fibrosis (NSF)?

PMID- 17018302
TI  - Late relapse of metastatic non-seminomatous testicular germ cell tumours.
AB  - Although the majority of men presenting with non-seminomatous germ cell tumours
      (NSGCT) are cured, late relapse (occurring more than 2 years after obtaining a
      complete response to treatment) is increasingly recognized. The typical patterns
      of disease spread have been well-documented, but the findings at late relapse are
      more variable and less well-described. We discuss the phenomenon of late relapse,
      the characteristics of teratoma differentiated (TD), and the issue of long-term
      imaging surveillance of patients with NSGCT. The potential sites of late relapse
      of NSGCT and the associated spectrum of imaging appearances are illustrated.

PMID- 17018303
TI  - Clarifying margins in the multidisciplinary management of rectal cancer: the
      MERCURY experience.
AB  - The Magnetic Resonance Imaging and Rectal Cancer European Equivalence Study
      (MERCURY) was an observational prospective study involving 11 European centres,
      to evaluate equivalence between magnetic resonance imaging and histopathology in
      measuring depth of tumour invasion beyond the bowel and involvement of the
      circumferential resection margin in rectal cancer specimens.

PMID- 17018304
TI  - Diagnostic value of multidetector row CT in rectal cancer staging: comparison of
      multiplanar and axial images with histopathology.
AB  - AIM: Although magnetic resonance (MR) imaging is widely used for rectal cancer
      staging, many centres in the UK perform computed tomography (CT) for staging
      rectal cancer at present. Furthermore in a small proportion of cases
      contraindications to MR imaging may lead to staging using CT. The purpose of this
      study was to evaluate the accuracy of current generation multidetector row CT
      (MDCT) in local staging of rectal cancer. In particular the accuracy of
      multiplanar (MPR) versus axial images in the staging of rectal cancer was
      assessed. MATERIAL AND METHODS: Sixty-nine consecutive patients were identified
      who had undergone staging of rectal cancer on CT. The imaging data were reviewed
      as axial images and then as MPR images (coronal and sagittal) perpendicular and
      parallel to the tumour axis. CT staging on axial and MPR images was then compared
      to histopathological staging. RESULTS: MPR images detected more T4 and T3 stage
      tumours than axial images alone. The overall accuracy of T-staging on MPR images
      was 87.1% versus 73.0% for axial images alone. The overall accuracy of N staging
      on MPR versus axial images was 84.8% versus 70.7%. There was a statistically
      significant difference in the staging of T3 tumours between MPR and axial images
      (p<0.001). CONCLUSION: Multidetector row CT has high accuracy for local staging
      of rectal cancer. Addition of MPR images to standard axial images provides higher
      accuracy rates for T and N staging of rectal cancer than axial images alone.

PMID- 17018305
TI  - Computed tomographic colonography (CTC) performance: one-year clinical follow-up.
AB  - AIM: Computed tomographic colonography (CTC) represents a valuable advance in
      imaging technology for patients with colonic symptoms who are unfit for or fail
      to complete investigation with conventional techniques of colonoscopy or barium
      enema. The aim of this study was to examine whether CTC was sufficient to exclude
      colorectal cancer in such a population. As our patients were unfit for or unable
      to complete conventional investigations, we used 1 year clinical follow-up to
      exclude colonic malignancy. MATERIALS AND METHODS: CTC examination was performed
      using multi-slice CT in patients fitting pre-determined criteria. All patients
      who had completed 12 months of follow-up after CTC were included. Data were
      extracted from patient records and lack of presentation within the 12 months
      following a negative CTC was assumed to equate to lack of colorectal cancer at
      initial investigation. RESULTS: One hundred and twelve patients underwent CTC
      with a median age of 78 years (range 39-95) and median follow-up of 18 months
      (range 12-26). CTC detected 7 colorectal cancers, with 3 false positives and 1
      false negative, giving a sensitivity of 87.5% and specificity of 97.1% for the
      detection of colorectal cancer. CONCLUSIONS: CTC is a good imaging tool for the
      exclusion of colorectal cancer in a population unfit for or unable to complete
      colonoscopy or barium enema, with reasonable sensitivity and specificity for
      detection of colorectal cancer. However, the optimum investigative strategy for
      fitter symptomatic individuals is still debated and should be clarified by the
      results of ongoing randomised controlled trials.

PMID- 17018306
TI  - Technical inadequacies of peripheral contrast-enhanced magnetic resonance
      angiography: incidence, causes and management strategies.
AB  - AIM: To assess the incidence, causes and effects of technical inadequacies in
      peripheral contrast-enhanced magnetic resonance angiography (CE-MRA) and to
      discuss relevant management strategies. MATERIALS AND METHODS: A retrospective
      analysis of 249 peripheral CE-MRA examinations was performed using the radiology
      department's RIS/PACS (radiology information system/picture archiving and
      communication system) database. All failed or technically inadequate MRAs were
      reviewed. In cases that underwent further imaging by conventional angiography
      (CA), we assessed if relevant arterial disease had been masked on the MRA.
      RESULTS: Of the 249 examinations, 215 (86.3%) were technically satisfactory while
      34 (13.7%) were a combination of technical inadequacies [29 cases (11.6%)] and
      examination failures [five cases (2%)]. The causes of technical inadequacies
      were: (1) venous contamination (13 cases; 5.2%), (2) motion-induced subtraction
      artefact (eight cases; 3.2%), (3) stent-induced artefact (four cases; 1.6%), (4)
      inadequate scan coverage (two cases; 0.8%), and (5) contrast timing error (two
      cases; 0.8%). The causes of failed examinations were: (1) inability to tolerate
      lying in the scanner (three cases; 1.2%) and (2) inability to fit into the
      scanner (two cases; 0.8%). Fifteen (44.1%) of the 34 cases underwent further
      imaging by CA, and in eight of these there was significant arterial disease that
      was missed on the MRA. CONCLUSION: Technical inadequacies occur in a small but
      significant proportion of peripheral CE-MRAs and can mask significant arterial
      disease. Knowledge of the potential causes of technical problems and the relevant
      management options is important for quality assurance and for limiting the need
      for an alternative investigation.

PMID- 17018307
TI  - MRI accuracy in residual disease evaluation in breast cancer patients treated
      with neoadjuvant chemotherapy.
AB  - AIM: To assess the accuracy of magnetic resonance imaging (MRI) in evaluating
      residual disease after neoadjuvant chemotherapy in patients with large breast
      cancers. MATERIALS AND METHODS: Forty-five women with large breast cancers
      underwent MRI mammography before and after neoadjuvant chemotherapy (three or six
      cycles). Dynamic MRI was performed using a 1.5 T unit using three-dimensional
      FSPGR sequences. For each patient tumour size, tumour volume and dynamic curve
      were obtained before and after neoadjuvant treatment. Residual tumour sizes
      obtained using MRI were compared with pathological findings to assess the
      accuracy of MRI in detecting and in measuring residual tumour. RESULTS: The
      sensitivity, specificity and accuracy of MRI in detecting residual disease was
      90.5, 100, and 91.3%, respectively. The mean of largest diameters measured at
      histology and at MRI were 26 and 28.2mm, respectively. The tumour size
      correlation coefficient between MRI and pathology measurements was very high:
      r(2)=0.9657 (p<0.0001). The interclass correlation coefficient between
      preoperative imaging measurements and pathological measurements of residual
      disease was 0.944 (95% CI: 0.906-0.982). CONCLUSION: The presence and size of
      residual disease in breast patients treated with neoadjuvant chemotherapy could
      be accurately evaluated using MRI.

PMID- 17018308
TI  - The wandering spleen: CT findings and possible pitfalls in diagnosis.
AB  - AIM: To report the CT features of wandering spleen, a rare condition which can be
      incidentally detected as an abdominal or pelvic mass or can present with torsion,
      causing an acute abdomen. MATERIALS AND METHODS: The CT studies of seven
      patients, two children and five adults, with wandering spleen were reviewed. CT
      was performed urgently in three patients for acute abdomen, and electively in
      four. RESULTS: CT findings of wandering spleen included absence of the spleen in
      its normal position and a mass located elsewhere in the abdomen or pelvis, i.e.
      an ectopic spleen, enhancing homogeneously in four cases and failing partially or
      completely to enhance in the other three, indicating infarction. A "whirl"
      appearance representing the twisted splenic pedicle was seen in the three cases
      with torsion. Urgent splenectomy confirmed infarction secondary to torsion.
      CONCLUSION: The possible diagnosis of wandering spleen should be kept in mind
      when CT shows the spleen to be absent from its usual position and a mass is found
      elsewhere in the abdomen or pelvis. When, in addition, a "whirl" or partial or no
      enhancement of this mass are seen in a case presenting with acute abdomen,
      torsion of a wandering spleen is a likely diagnosis.

PMID- 17018309
TI  - Single breath-hold diffusion-weighted MRI of the liver with parallel imaging:
      initial experience.
AB  - AIM: To evaluate prospectively the improvement in the signal:noise ratio (SNR),
      with the use of parallel technique in single breath-hold diffusion-weighted
      imaging (DWI) of the liver and its affect on apparent diffusion coefficient (ADC)
      measurements. MATERIALS AND METHODS: This study was approved by our institutional
      review board. Written informed consent was obtained from all participants.
      Fifteen patients underwent single breath-hold DWI of the liver with and without
      parallel imaging technique. SNR and ADC values were measured over a lesion-free
      right hepatic lobe by two radiologists in both series. When a focal hepatic
      lesion was present the contrast:noise ratio (CNR) and ADC were also measured.
      Paired Student's t-tests were used for statistical analysis. RESULTS: Mean SNR
      values of the liver were 20.82+/-7.54 and 15.83+/-5.95 for DWI with and without
      parallel imaging, respectively. SNR values measured in DWI using parallel imaging
      were found to be significantly higher (p<0.01). Mean ADC of the liver were 1.61+/
      0.45 x 10(-3)mm(2)/s and 1.56+/-0.28 x 10(-3)mm(2)/s for DWI with and without
      parallel imaging, respectively. No significant difference was found between the
      two sequences for hepatic ADC measurement (p>0.05). Overall lesion CNR was found
      to be higher in DWI with parallel imaging. CONCLUSION: Parallel imaging is useful
      in improving SNR of single breath-hold DWI of the liver without compromising ADC
      measurements.

PMID- 17018310
TI  - Polyethylene glycol solution as an oral contrast agent for MRI of the small bowel
      in a patient population.
AB  - AIM: To assess the efficacy of polyethylene glycol solution as an oral contrast
      agent in a patient population. MATERIAL AND METHODS: Patients were fasted from
      12.00 am. Administration of the oral contrast medium commenced 15 min before
      imaging and comprised one sachet of Norgine (Klean-prep, Middlesex, UK)
      reconstituted in 1 l water of which the patient took between 500-750 ml. Norgine
      is a balanced mixture of polyethylene glycol and electrolytes, which when added
      to water produces a clear colourless, iso-osmotic solution. RESULTS: In total 38
      candidates were identified retrospectively covering a 2-year period.
      Visualization of the jejunum, ileal loops and ileocaecal region was excellent or
      sufficient in 87, 95 and 89%, respectively. The time taken to obtain complete
      visualization of the small bowel, from the jejunum to the ileocecal region varied
      from 15-240 min with an average time of 65 min and 73.7% of patients
      necessitating delayed imaging. CONCLUSIONS: Polyethylene glycol was demonstrated
      to be an excellent oral contrast medium in distending the small bowel. However,
      small bowel transit times were significantly delayed and problematic
      necessitating repeated imaging within the patient population. As result of theses
      findings longer examination time should be expected within a patient population
      and this should be borne in mind when scheduling patients.

PMID- 17018311
TI  - Evaluation of three different measurement methods for dural ectasia in Marfan
      syndrome.
AB  - AIM: Dural ectasia is a major diagnostic criterion for Marfan syndrome using the
      Ghent nosology. Our aim was to evaluate the efficacy of three different
      radiological methods previously proposed for the assessment of dural sac diameter
      in Marfan syndrome. METHODS: Marfan syndrome was diagnosed in our study using the
      Ghent criteria, disregarding dural ectasia as a criterion. Three proposed
      radiological methods were applied to measure dural sac diameter, examined for 41
      patients (18 patients with and 23 without Marfan syndrome) by computed tomography
      or magnetic resonance imaging. RESULTS: Using Oosterhof's method, 94% of the
      patients with and 44% of the patients without Marfan syndrome fulfilled the
      criteria of dural ectasia. According to Villeirs, dural ectasia was diagnosed in
      18% of the patients with and in none of the patients without Marfan syndrome.
      With Ahn's method, dural ectasia was found in 72% of the patients with and in 44%
      of the patients without Marfan syndrome. In only two patients with Marfan
      syndrome was dural ectasia diagnosed by all three methods. CONCLUSION: Our
      results reveal overt discrepancy between the three methods of assessing dural
      ectasia. Considering the key role played by dural ectasia in reinforcing the
      diagnosis of Marfan syndrome according to the Ghent nosology, a standardized and
      reliable method should be sought.

PMID- 17018312
TI  - Angiotensin-converting enzyme inhibitor-induced visceral angioedema.

PMID- 17018313
TI  - Isolated cerebellar involvement in a case of posterior reversible
      leukoencephalopathy.

PMID- 17018314
TI  - Guided leadership.

PMID- 17018320
TI  - How (& when) to give orders.

PMID- 17018319
TI  - Limits of medical direction.

PMID- 17018321
TI  - How'd that go? 3 great words to start a critique.

PMID- 17018322
TI  - Another case of atrial fibrillation?

PMID- 17018323
TI  - Protocol blues. Using research to bring change into your system.

PMID- 17018324
TI  - 2006 JEMS Salary & Workplace Survey. Training, diversity, recruitment & injuries
      surface as action areas.

PMID- 17018325
TI  - What now for AutoPulse? Contradictory studies create confusion for EMS systems.

PMID- 17018327
TI  - Casino syncope.

PMID- 17018329
TI  - A series of three sequential, randomized, controlled studies of repeated
      treatments with botulinum toxin type A for migraine prophylaxis.
AB  - We examined the effects of multiple treatments with low doses of botulinum toxin
      type A (BoNTA; BOTOX(R), Allergan Inc., Irvine, CA) versus placebo for
      prophylaxis of episodic migraine. This was a series of 3 sequential, randomized,
      controlled studies of 418 patients with a history of 4 to 8 moderate to severe
      migraines per month. In study I, patients were randomized to treatment with
      placebo or BoNTA (7.5 U, 25 U, or 50 U) in predetermined fixed injection sites on
      the front and sides of the head only. In study II, patients continued to receive,
      or were randomized to, 2 consecutive treatments with 25 U or 50 U. In study III,
      patients were randomized to placebo or continuation of 25 U or 50 U. Injection
      cycles were each 4 months long. BoNTA and placebo produced comparable decreases
      from baseline in the frequency of migraines at each time point examined (P >or=
      .201). No consistent, statistically significant differences were observed for any
      efficacy variable. Adverse events were similar among the groups within each
      study. In these exploratory studies of episodic migraine patients, repeated
      injections of low doses of BoNTA into fixed frontal, temporal, and glabellar
      sites were not more effective than placebo. BoNTA was safe and well tolerated.
      PERSPECTIVE: Beneficial effects of BoNTA in the treatment of migraine have been
      reported, but positive results are not universal, possibly because the optimal
      patient population and regimen are not yet definitively established. This study
      explores the effects of multiple injections of low BoNTA doses into fixed sites
      for episodic migraine.

PMID- 17018330
TI  - Catastrophizing and pain-contingent rest predict patient adjustment in men with
      chronic prostatitis/chronic pelvic pain syndrome.
AB  - Cognitive/behavioral and environmental variables are significant predictors of
      patient adjustment in chronic pain. Using a biopsychosocial template and
      selecting several pain-relevant constructs from physical, cognitive/behavioral,
      and environmental predictors, outcomes of pain and disability in chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS) were explored. Men (n = 253)
      from a North American multi-institutional NIH-funded Chronic Prostatitis Cohort
      Study in 6 US and 1 Canadian centers participated in a survey examining pain and
      disability. Measures included demographics, urinary symptoms, depression, pain,
      disability, catastrophizing, control over pain, pain-contingent rest, social
      support, and solicitous responses from a significant other. Regressions showed
      that urinary symptoms (beta = .20), depression (beta = .24), and helplessness
      catastrophizing (beta = .29) predicted overall pain. Further, affective pain was
      predicted by depression (beta = .39) and helplessness catastrophizing (beta =
      .44), whereas sensory pain was predicted by urinary symptoms (beta = .25) and
      helplessness catastrophizing (beta = .37). With regard to disability, urinary
      symptoms (beta = .17), pain (beta = .21), and pain-contingent rest (beta = .33)
      were the predictors. These results suggest cognitive/behavioral variables (ie,
      catastrophizing, pain-contingent rest) may have significant impact on patient
      adjustment in CP/CPPS. Findings support the need for greater research of such
      pain-related variables in CP/CPPS. PERSPECTIVE: This article explores predictors
      of patient adjustment in chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS). Cognitive/behavioral variables of catastrophizing and pain-contingent
      rest respectively predicted greater pain and disability. Catastrophic
      helplessness was a prominent pain predictor. These findings inform clinicians and
      researchers on several new variables in CP/CPPS outcomes and suggest future
      research.

PMID- 17018331
TI  - Anticipatory electroencephalography alpha rhythm predicts subjective perception
      of pain intensity.
AB  - This high-resolution electroencephalography (EEG) study tested the hypothesis
      that the suppression of rolandic alpha power before predictable painful
      stimulation affects the subject's subsequent evaluation of pain intensity, as a
      reflection of the influence of expectancy processes on painful stimulus
      processing. High-resolution EEG data were recorded (126 channels) from 10 healthy
      adult volunteers during the expectancy of a painful CO(2)-laser stimulation at
      the right wrist. Surface laplacian estimation enhanced the EEG spatial
      information content over 6 scalp regions of interest (left frontal, right
      frontal, left central, right central, left parietal, and right parietal areas).
      Spectral power was computed for 3 alpha sub-bands with reference to the
      individual alpha frequency peak (about 5-7 Hz for alpha 1, 7-9 Hz for alpha 2,
      and 9-11 Hz for alpha 3). The suppression of the alpha power before the painful
      stimulation [as reflected by the event-related desynchronization (ERD)] indexed
      the anticipatory cortical processes. Results showed maximum (negative)
      correlations between the alpha 2 and alpha 3 ERD amplitude at the left central
      area and the subjective evaluation of pain intensity (P < .001). The stronger the
      anticipatory alpha 2 and alpha 3 ERD, the higher the subjective evaluation of
      pain intensity. For alpha 3, that correlation was confirmed even when the effect
      of habituation across the recording session was taken into account. These results
      suggest that the anticipatory suppression of the alpha rhythms over the
      contralateral primary sensorimotor cortex predicts subsequent subjects'
      evaluation of pain intensity, in line with its crucial role for the
      discrimination of that intensity. PERSPECTIVE: This electroencephalographic study
      showed that anticipatory activation/deactivation of sensorimotor cortex roughly
      predicts subjective evaluation of pain. This motivates further investigation on
      possible implications for the understanding of central chronic pain. Chronic pain
      patients might exaggerate the anticipatory activation of sensorimotor cortex to
      negligible pain stimuli.

PMID- 17018332
TI  - Factors associated with early opioid prescription among workers with low back
      injuries.
AB  - Prescription of opioids for nonmalignant musculoskeletal pain has increased
      substantially in recent years, but there is little information on the incidence
      of, or factors associated with, such prescription for work-related back pain. In
      a prospective cohort study (N = 1,067), we examined associations between worker
      sociodemographic and other characteristics and opioid prescription within six
      weeks of the first medical visit for workers' compensation claims for work loss
      due to back injury. We examined administrative, pharmacy, and worker-reported
      data. In bivariate logistic regression models, Hispanics were less likely than
      non-Hispanic whites to receive opioid prescriptions, and very high body mass
      index, daily tobacco use, greater pain and physical disability, pain radiating
      below the knee, injury severity categorizations (from medical records) of major
      sprain and radiculopathy, and worse mental health were associated with opioid
      prescription. Adjusting for demographics, pain intensity, and physical
      disability, opiate prescription was significantly associated with daily tobacco
      use, pain radiating below the knee, and injury severity categories (major sprain
      and radiculopathy). Knowledge of worker characteristics associated with early
      opioid prescription may be useful in future studies of the role of early pain
      treatment in influencing subsequent course of pain and disability among workers
      with back injuries. PERSPECTIVE: Little is known about patient characteristics
      that may influence physicians' decisions concerning prescription of opioids for
      acute back pain. Not surprisingly, workers with more severe back injuries are
      more likely to be prescribed opioids, but reasons for prescription disparities
      based on ethnicity and tobacco use warrant further study.

PMID- 17018333
TI  - Concerns about medication and medication use in chronic pain.
AB  - This report describes a study of how patients view their pain medications. Two
      hundred and twenty patients with chronic pain completed a set of 78 items
      regarding beliefs and concerns about pain medication, a brief measure of
      medication use, and measures of depression and disability. Item and scale
      analyses resulted in a 47-item measure, the Pain Medication Attitude
      Questionnaire (PMAQ), that assesses 7 areas of patient concern: addiction,
      perceived need, unfavorable scrutiny by others, adverse side effects, tolerance,
      mistrust in the prescribing doctor, and withdrawal. These seven scales had
      excellent internal consistency and predictable relations with the measures of
      medication use, depression, and disability supporting their validity. Correlation
      analyses highlighted relatively strong associations between concerns about
      medication and measures of emotional distress and disability, suggesting that
      these concerns may add significantly to the burden of chronic pain. We suggest
      that concerns about medication use warrant further study and may deserve clinical
      attention. PERSPECTIVE: All medication use by chronic pain sufferers is
      essentially a pattern of patient behavior over time. As such, it appears to be
      multiply-determined, by beliefs, emotions, bodily sensations, and the social,
      cultural, and personal learning history that give these experiences their meaning
      and functions.

PMID- 17018334
TI  - Design and characterization of a noncompetitive antagonist of the transient
      receptor potential vanilloid subunit 1 channel with in vivo analgesic and anti
      inflammatory activity.
AB  - Vanilloid receptor subunit 1 (TRPV1) is an integrator of physical and chemical
      stimuli in the peripheral nervous system. This receptor plays a key role in the
      pathophysiology of inflammatory pain. Thus, the identification of receptor
      antagonists with analgesic and anti-inflammatory activity in vivo is an important
      goal of current neuropharmacology. Here, we report that [L-arginyl]-[N-[2,4
      dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl) glycinamide (H-Arg-15-15C) is
      a channel blocker that abrogates capsaicin and pH-evoked TRPV1 channel activity
      with submicromolar activity. Compound H-Arg-15-15C preferentially inhibits TRPV1,
      showing marginal block of other neuronal receptors. Compound H-Arg-15-15C acts as
      a noncompetitive capsaicin antagonist with modest voltage-dependent blockade
      activity. The compound inhibited capsaicin-evoked nerve activity in afferent
      fibers without affecting mechanically activated activity. Notably, administration
      of compound H-Arg-15-15C prevented the irritant activity of a local
      administration of capsaicin and formalin and reversed the thermal hyperalgesia
      evoked by injection of complete Freund's adjuvant. Furthermore, it attenuated
      carrageenan-induced paw inflammation. Compound H-Arg-15-15C specifically
      decreased inflammatory conditions without affecting normal nociception. Taken
      together, these findings demonstrate that compound H-Arg-15-15C is a channel
      blocker of TRPV1 with analgesic and anti-inflammatory activity in vivo at
      clinically useful doses and substantiate the tenet that TRPV1 plays an important
      role in the etiology of chronic inflammatory pain. PERSPECTIVE: This study
      reports the design of a potent TRPV1 noncompetitive antagonist that exhibits anti
      inflammatory and analgesic activity in preclinical models of acute and chronic
      pain. This compound is a lead for analgesic drug development.

PMID- 17018335
TI  - Central metabotropic glutamate receptors differentially participate in
      interleukin-1beta-induced mechanical allodynia in the orofacial area of conscious
      rats.
AB  - The present study investigated the role of central metabotropic glutamate
      receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia
      and mirror-image mechanical allodynia in the orofacial area. Experiments were
      carried out on male Sprague-Dawley rats weighing 230 to 280 g. After
      administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of
      the vibrissa pad, we examined the withdrawal behavioral responses produced by 10
      successive trials of an air-puff ramp pressure applied ipsilaterally or
      contralaterally to the IL-1beta injection site. Subcutaneous injection of IL
      1beta produced mechanical allodynia and mirror-image mechanical allodynia in the
      orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or
      MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and
      mirror-image mechanical allodynia. Intracisternal administration of APDC, a group
      II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta
      induced mechanical allodynia and mirror-image mechanical allodynia. The
      antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal
      pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III
      mGluR antagonist. These results suggest that groups I, II, and III mGluRs
      differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror
      image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I
      mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced
      mechanical allodynia and mirror-image mechanical allodynia in the orofacial area.
      Therefore, the central application of group I mGluR antagonists or groups II and
      III mGluR agonists might be of therapeutic value in treating pain disorder.

PMID- 17018336
TI  - Spinal cord glia and interleukin-1 do not appear to mediate persistent allodynia
      induced by intramuscular acidic saline in rats.
AB  - Spinal glial activation and consequent interleukin-1 (IL-1) release are
      implicated in pain facilitation induced by inflammation/damage to skin and
      peripheral nerves. It is unclear whether pain facilitation induced at deep tissue
      sites also depends on these. We investigated whether spinal IL-1 and/or glial
      activation mediates bilateral allodynia induced by repeated unilateral
      intramuscular injections of acidic saline to rats. Given the prominent role of
      spinal IL-1 in various bilateral pain models, we predicted that intrathecal IL-1
      receptor antagonist (IL-1ra) would suppress bilateral allodynia in this model as
      well. Surprisingly, neither single nor repeated intrathecal injections of IL-1ra
      affected allodynia, measured by the von Frey test, induced by prior intramuscular
      acidic saline compared with vehicle-injected controls. In addition, we tested the
      effect of 2 additional intrathecal manipulations that are broadly efficacious in
      suppressing glially mediated pain facilitation: (1) a glial metabolic inhibitor
      (fluorocitrate) and (2) the anti-inflammatory cytokine, interleukin-10 (IL-10).
      Like IL-1ra, fluorocitrate and IL-10 each failed to reverse allodynia. Finally,
      we observed no significant activation of glial cells, as assessed by
      immunohistochemistry of glial activation markers, in the lumbar spinal cord in
      response to intramuscular acidic saline. Taken together, the present data suggest
      that acidic saline-induced bilateral allodynia is created independently of glial
      activation. PERSPECTIVE: From converging lines of evidence, the current studies
      suggest that persistent bilateral allodynia induced by repeated intramuscular
      acidic saline is not mediated by spinal IL-1 and/or spinal glial activation. As
      such, this might represent the first evidence for pain facilitation occurring in
      the absence of glial involvement.

PMID- 17018339
TI  - Twelve-lead ECG features to identify ventricular tachycardia arising from the
      epicardial right ventricle.
AB  - BACKGROUND: Usefulness of 12-lead ECG for predicting an epicardial origin for
      ventricular tachycardia (VT) arising from the right ventricle (RV) has not been
      assessed. An epicardial approach is sometimes warranted to eliminate RV VT.
      OBJECTIVES: The purpose of this study was investigate the hypothesis that
      specific ECG features identify an epicardial origin for RV VT. METHODS: To mimic
      an endocardial or epicardial origin, we paced representative sites in 13 patients
      undergoing RV endocardial/epicardial mapping (134/180 pace map sites). RESULTS:
      QRS duration from epicardial vs endocardial sites was not different (183 +/- 27
      ms vs 185 +/- 28 ms, P = .3). Reported cut-off values for identifying epicardial
      left ventricular origin, pseudo-delta wave (> or =34 ms), intrinsicoid deflection
      time (> or =85 ms), and RS complex (> or =121 ms) did not apply to the RV. A Q
      wave in lead II, III, or aVF was more likely noted from inferior epicardial vs
      endocardial sites (53/73 vs 16/43, P <.01). A Q wave in lead I was more
      frequently present from epicardial vs endocardial anterior RV sites (30/82 vs
      5/52, P <.001). QS in lead V(2) was noted from anatomically matched epicardial
      anterior RV sites (22/33 vs 13/33, P <.05). In the RV outflow tract, no ECG
      feature distinguishing epicardial/endocardial origin reached statistical
      significance. CONCLUSION: A Q wave or QS in leads that best reflect local
      activation suggest an epicardial origin for RV depolarization and may help in
      identifying a probable epicardial site of origin for RV VT. QRS duration and
      reported criteria for epicardial origin of VT in the left ventricle do not
      identify a probable epicardial origin in the RV.

PMID- 17018337
TI  - The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of
      postoperative pain.
AB  - Non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonists modify
      multiple pain transmission pathways and are of particular interest in analgesic
      development because of their capacity to interfere with evoked pain. Evoked pain
      is a problem for postoperative patients and is characteristic of the plantar
      incision model for postoperative pain. The purpose of this study was to assess
      the efficacy of a non-NMDA receptor antagonist LY293558 on mechanical
      hyperalgesia after plantar incision in the rat. Parenteral, intrathecal, or
      intraplantar administration of LY293558 was tested against the mechanical
      hyperalgesia that characterizes the model. Sprague-Dawley rats were assigned to 1
      of 3 groups. LY293558 or vehicle was administered intraperitoneally,
      intrathecally, or intraplantarly. The hind paw withdrawal threshold to punctate
      stimulation by using von Frey filaments and response frequency to a nonpunctate
      stimulus directly to the wound were measured. Motor tests after administration of
      LY293558 were also examined in rats that did not undergo incision. The greatest
      dose of parenterally administered LY293558 (34 micromol/kg) decreased the
      responses to mechanical stimuli after plantar incision. Rotorod performance was
      decreased at these same times. Intrathecal injection of LY293558 (0.5 and 2.0
      nmol) produced inhibition of mechanical sensitivity and produced lower extremity
      motor side effects. Repeated intrathecal administration produced sustained
      anesthesia for 24 hours but had no analgesic effect the next day. Local
      administration did not decrease response after incision. LY293558 was most
      effective for evoked pain when administered intrathecally. PERSPECTIVE: Control
      of evoked pain after surgery is inadequate but is linked to perioperative
      outcome. These data suggest that non-NMDA receptor antagonists like LY293558 will
      be most effective for evoked pain in postoperative patients if administered
      spinally.

PMID- 17018340
TI  - Nonexcitatory, cardiac contractility modulation electrical impulses: feasibility
      study for advanced heart failure in patients with normal QRS duration.
AB  - BACKGROUND: Cardiac contractility modulation signals are associated with acutely
      improved hemodynamics, but chronic clinical impact is not defined. OBJECTIVES:
      The purpose of this randomized, double-blind, pilot study was to determine the
      feasibility of safely and effectively delivering cardiac contractility modulation
      signals in patients with heart failure. METHODS: Forty-nine subjects with
      ejection fraction <35%, normal QRS duration (105 +/- 15 ms), and New York Heart
      Association (NYHA) class III or IV heart failure despite medical therapy received
      a cardiac contractility modulation pulse generator. Patients were randomized to
      have their devices programmed to deliver cardiac contractility modulation signals
      (n = 25, treatment group) or to remain off (n = 24, control group) for 6 months.
      Evaluations included NYHA class, 6-minute walk, cardiopulmonary stress test,
      Minnesota Living with Heart Failure Questionnaire, and Holter monitoring.
      RESULTS: Although most baseline features were balanced between groups, ejection
      fraction (31.4% +/- 7.4% vs 24.9% +/- 6.5%, P = .003), end-diastolic dimension
      (52.1 +/- 21.4 mm vs 62.5 +/- 6.2 mm, P = .01), peak VO(2) (16.0 +/- 2.9 mL
      O(2)/kg/min vs 14.3 +/- 2.8 mL O(2)/kg/min, P = .02), and anaerobic threshold
      (12.3 +/- 2.5 mL O(2)/kg/min vs 10.6 +/- 2.4 mL O(2)/kg/min, P = .01) were worse
      in the treatment group than in the control group. Nevertheless, one death
      occurred in the control group, and more patients in the treatment group were free
      of hospitalization for any cause at 6 months (84% vs 62%). No change in ectopy
      was observed. Compared with baseline, 6-minute walk (13.4 m), peak VO(2) (0.2 mL
      O(2)/kg/min), and anaerobic threshold (0.8 mL O(2)/kg/min) increased more in the
      treatment group than in control. None of these differences were statistically
      significant (small sample size). NYHA and Minnesota Living with Heart Failure
      Questionnaire changed similarly in the two groups. CONCLUSION: Despite a sicker
      population in the treatment group, no specific safety concerns emerged with
      chronic cardiac contractility modulation signal administration. Further study is
      required to definitively define the safety and efficacy of cardiac contractility
      modulation signals.

PMID- 17018341
TI  - Cardiac contractility modulation: A new technologically advanced placebo?

PMID- 17018342
TI  - Radiofrequency catheter ablation and nerve growth factor concentration in humans.
AB  - BACKGROUND: In animal models, expression of nerve growth factor (NGF) is
      increased after necrotic myocardial injury. Whether radiofrequency (RF) catheter
      ablation increases NGF expression in humans is unclear. OBJECTIVES: The purpose
      of this study was to determine NGF concentrations in the aorta, coronary sinus,
      and peripheral veins before and after RF ablation in patients. METHODS: We
      sampled blood from aorta and either great cardiac vein (group 1, N = 18) or
      proximal (group 2, N = 20) coronary sinus before and after RF ablation. In group
      3 (N = 21), peripheral venous blood was sampled before and after RF ablation and
      then up to postoperative day 7. In group 4 (N = 10), we sampled peripheral venous
      blood during diagnostic electrophysiologic study. The NGF concentration was
      determined by enzyme-linked immunosorbent assay. Transcardiac NGF concentration
      was the difference in NGF concentrations between coronary sinus and aorta.
      RESULTS: There was no change in transcardiac NGF concentrations in groups 1 and
      2. In group 3, the NGF level did not change significantly from before the
      procedure (17.10 +/- 15.80 ng/mL) to immediately after the procedure (14.46 +/-
      10.36 ng/mL). However, NGF levels increased significantly to 31.24 +/- 19.82
      ng/mL (N = 21, P <.0001) on postoperative day 1, 26.23 +/- 16.89 ng/mL (N = 20, P
      <.001) on postoperative day 2, and 22.01 +/- 11.35 ng/mL (N = 16, P = .003) on
      postoperative day 3. NGF concentrations did not change significantly in group 4.
      CONCLUSION: RF ablation did not result in a detectable increase of transcardiac
      NGF concentration immediately after the procedure. However, the systemic NGF
      concentration increased significantly on postoperative days 1 to 3, suggesting
      that RF ablation resulted in increased NGF expression.

PMID- 17018343
TI  - Esophageal imaging and strategies for avoiding injury during left atrial ablation
      for atrial fibrillation.
AB  - BACKGROUND: Part of the esophagus is contiguous to the posterior wall (PW) of the
      left atrium (LA). Esophageal injury has occurred during LA ablation for atrial
      fibrillation (AF). The ability to identify the esophagus and monitor LAPW lesions
      with intracardiac echocardiography (ICE) has not been documented. METHODS: We
      report an index case of atrioesphageal fistula as a complication of transcatheter
      ablation of AF. After the index case, we retrospectively reviewed morphologic
      changes with radiofrequency (RF) delivered at LAPW during pulmonary vein (PV)
      electrical isolation using an 8-mm tip electrode (up to 70 W at a maximum of 50
      52 degrees C for 60 seconds) or Chilli catheter (up to 50 W at a maximum of 40
      degrees C for 60 seconds). ICE did not influence lesion application. After the
      index case, RF power was reduced at areas adjacent to the esophagus (8 mm/30-50 W
      at 50 degrees C or Chilli/40 W at a maximum of 38 degrees C). Duration of RF, 10
      30 seconds, was titrated based on accelerated bubble formation or early echogenic
      lesion formation. RESULTS: The longitudinal extent of the contiguous LAPW
      esophageal wall (length 18-59 mm) was identified in all 152 patients (ages 56 +/-
      10 years, 117 men). Preablation LAPW (2.8 +/- 0.7 mm) and contiguous anterior
      esophageal wall (3.0 +/- 0.8 mm) thickness were noted. A total of 6 +/- 4.9
      lesions/patient were delivered to the LAPW contiguous to the esophagus. Echogenic
      LAPW thickness increased to 7.5 +/- 2.1 mm (vs. 2.8 +/- 0.5 mm preablation)
      before the index case (n = 70 patients) and 4.7 +/- 1.6 mm (vs. 2.9 +/- 0.6 mm)
      after the index case (n = 67), with power reduction and titration of duration of
      energy delivery RF (P <.01) and PV isolation in all. CONCLUSIONS: The LAPW
      esophageal region can be identified and monitored with ICE imaging during
      ablation procedures. RF lesions to the LAPW in PV isolation can produce dramatic
      morphologic changes immediately adjacent to the anterior esophageal wall. A
      reduction in power amount and duration as described coupled with online lesion
      monitoring to further titrate duration (<30 seconds) of power delivery decreases
      the depth of lesion formation and limits the risk of esophageal involvement.

PMID- 17018344
TI  - Prevention of esophageal injury during catheter ablation of atrial fibrillation:
      is intracardiac echocardiography the answer?

PMID- 17018346
TI  - Pacing prevention of atrial fibrillation: is it ready for the prime time?

PMID- 17018345
TI  - Reduction of atrial tachyarrhythmia episodes during the overdrive pacing period
      using the post-mode switch overdrive pacing (PMOP) algorithm.
AB  - BACKGROUND: Early recurrences within 10 minutes after termination of an atrial
      tachyarrhythmia, such as atrial tachycardia (AT), atrial flutter, or atrial
      fibrillation (AF) episodes, account for a large part of paroxysmal AT/AF
      episodes. It is unclear whether these arrhythmias can be suppressed by overdrive
      pacing. OBJECTIVE: We set out to prove that overdrive pacing is effective in
      preventing early recurrences of AT/AF. METHODS: This AT500 (DDDRP device, Bakken
      Research Center Medtronic, Maastricht, The Netherlands) post-mode switch
      overdrive pacing (PMOP) study is a randomized controlled trial designed to test
      the efficacy of overdrive pacing on the suppression of early recurring AT/AF
      episodes. With the PMOP feature, overdrive pacing is activated 12 ventricular
      beats after device-confirmed termination of an AT/AF episode with a programmed
      duration and rate. If at least four episodes of 1 minute in duration occurred
      within the run-in period of 1 month, patients were randomized to one of the three
      settings (PMOP off and PMOP 10 minutes at 90 bpm or 120 bpm) for 2 months. At 2
      and 4 months, patients were crossed over to another arm. At 6 months, all
      patients were programmed with PMOP on at 90 bpm for 30 minutes. RESULTS: We
      enrolled 122 and randomized 50 patients. Sixty percent of all stored AT/AF
      episodes occurred within 10 minutes after a previous episode; 31% occurred after
      device-determined termination and before the device reached the overdrive rate
      (17-27 ventricular beats after termination), and 29% of the episodes occurred
      while the device was pacing at the programmed overdrive rate. Thirty-seven
      percent of the average percentage of episodes during the overdrive period was
      prevented by the randomized settings of PMOP 90 bpm/10 min (P = .01, paired t
      test, n = 39) and 120 bpm/10 min (P = .03, n = 35). In addition, for the
      nonrandomized setting of PMOP 90 bpm/30 min, the average number of episodes
      during the overdrive period was significantly smaller than the percentage of
      episodes occurring during the corresponding off period of 30 minutes (P = .05, n
      = 33). No significant differences in burden and episodes were found between the
      PMOP settings and the corresponding off periods. CONCLUSIONS: This is the first
      randomized controlled clinical trial to prove that overdrive pacing is effective
      in preventing early recurrences of AT/AF. However, shortcomings of the PMOP
      algorithm, such as late activation, need further improvement.

PMID- 17018347
TI  - Quantitative assessment of ST segment elevation in Brugada patients.
AB  - BACKGROUND: ST segment elevation in the right precordial leads constitutes the
      electrocardiogram (ECG) hallmark of Brugada syndrome (BS). This pattern is
      variable and can be concealed, but the magnitude and the cause of ST segment
      fluctuations have been poorly investigated. OBJECTIVE: Our goal was to quantify
      ST changes and to assess rate and autonomic influences on ST level. METHODS: A 12
      lead ECG was continuously recorded during 24 hours in 20 patients with BS (ages
      49 +/- 12) and 10 healthy subjects (ages 32 +/- 7). Using two-dimensional binning
      we obtained average QRS-T complexes every 30 minutes (time bins) and at different
      RR intervals (rate bins) for each subject. ST level was measured at five
      different points located 90, 100, 110, 120, and 140 ms after Q onset (Qo). In BS
      patients, the highest ST elevation was measured 110 ms after Qo (Qo+110).
      RESULTS: ST level changes between time points were significantly greater in
      patients with BS compared with control subjects: on lead V2, the range of ST
      level at Qo+110 was 264 +/- 85 microV in BS and 91 +/- 22 microV in control
      subjects (P <.01). In BS, ST level decreased with heart rate acceleration: the
      difference in ST level at Qo+110 for RR = 900 and 600 ms was 55 +/- 53 microV (P
      <.01). HFnu was positively, although weakly, correlated with ST level (R(2) =
      0.02, P <.01). CONCLUSIONS: ECG changes observed in patients with BS are related
      in part to heart rate influences on ST segment level. These spontaneous
      fluctuations over a 24-hour time period suggest that Holter recordings may
      improve the ECG diagnosis sensitivity in BS.

PMID- 17018348
TI  - Inappropriate sinus tachycardia may be related to an immunologic disorder
      involving cardiac beta andrenergic receptors.
AB  - BACKGROUND: The mechanisms underlying inappropriate sinus tachycardia are not
      fully known. An autonomic imbalance seems to play a role, but no attempts have
      been made to investigate a relationship between this arrhythmia and the
      antiautonomic membrane receptor antibodies found in other heart disorders and
      arrhythmias. OBJECTIVE: The purpose of this study was to investigate the
      prevalence and the functional and biochemical effects of circulating
      antiautonomic receptor antibodies in patients with inappropriate sinus
      tachycardia. METHODS: We studied 21 patients with inappropriate sinus tachycardia
      and 15 healthy volunteers. The chronotropic effects of the IgG fractions (also of
      affinity-purified anti-beta1 adrenergic receptor antibodies in selected cases)
      were assessed on cultured cardiomyocytes before and after exposure to atropine
      and propranolol. The effects of the IgG fractions from five patients and five
      healthy volunteers on cAMP production were evaluated in COS-7 cells transfected
      with genes encoding for beta1 or beta2 adrenergic receptor. RESULTS: The IgG
      fractions from patients with inappropriate sinus tachycardia exerted a positive
      chronotropic action with a high prevalence of anti-beta receptor antibodies (52%)
      and induced a clear-cut and long lasting increment of cAMP. No anti-M2
      cholinergic receptor antibodies were found. The IgG fractions from healthy
      volunteers did not contain antiautonomic receptor antibodies. CONCLUSIONS: Our
      results suggest, for the first time, a link between inappropriate sinus
      tachycardia and circulating anti-beta adrenergic receptor antibodies that induce
      a persistent increment in cAMP production. This finding offers new insight into
      the physiopathology of inappropriate sinus tachycardia with potential therapeutic
      consequences.

PMID- 17018349
TI  - Inappropriate sinus tachycardia and beta-receptor autoantibodies: a mechanistic
      breakthrough?

PMID- 17018350
TI  - High resistance of atrioventricular node to cryoablation: a great safety margin
      targeting perinodal arrhythmic substrates.
AB  - BACKGROUND: Findings from animal studies and small series of patients support the
      greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic
      substrates near the AV node. OBJECTIVES: The purpose of this study was to
      systematically evaluate the electrophysiologic effects of successive cryoenergy
      applications to the human AV node in order to better define the safety margin of
      cryothermal ablation. METHODS: In 15 patients referred for AV nodal ablation, 94
      cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip
      cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the
      triangle of Koch. RESULTS: Temporary effects on AV conduction were observed in 18
      (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were
      observed in 9 (9%) cryoablation applications. Persistent effects were associated
      with cryoablation at the superior third of the triangle of Koch (P = .05), nadir
      tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15
      seconds (P = .03). Temperature and effect onset time remained statistically
      significant after multivariate adjustment (P = .01 and .02, respectively).
      Overall, persistent complete AV block was achieved with cryoenergy in only one
      patient. In two additional patients, AV conduction remained modified. In the
      remaining patients, persistent complete AV block was achieved with radiofrequency
      (median one application per patient). CONCLUSION: The low rate of persistent AV
      conduction impairment observed with attempts to cryoablate the AV node supports a
      great safety margin of perinodal cryothermal ablation.

PMID- 17018351
TI  - Renal dialysis as a risk factor for appropriate therapies and mortality in
      implantable cardioverter-defibrillator recipients.
AB  - BACKGROUND: Patients with end-stage renal disease are at increased risk for
      sudden cardiac death, although the utility of implantable cardioverter
      defibrillators (ICDs) in these patients is unknown. OBJECTIVES: The purpose of
      this study was to evaluate whether end-stage renal disease is an independent risk
      factor for appropriate ICD therapy for ventricular tachycardia (VT) or
      ventricular fibrillation (VF) and to compare the long-term survival of ICD
      recipients with and without end-stage renal disease. METHODS: A retrospective
      cohort study was performed on ICD recipients at a single center. The primary
      endpoint was first appropriate ICD therapy for VT/VF. The secondary endpoint was
      survival. RESULTS: The study included 585 patients, 19 (3.2%) of whom had end
      stage renal disease prior to device implantation. Average follow-up time was 2.2
      +/- 2.4 years, during which time 156 patients (26.7%) received appropriate ICD
      therapy. End-stage renal disease was strongly associated with appropriate ICD
      therapy (hazard ratio 2.30, 95% confidence interval 1.17-4.54) and remained a
      significant predictor following adjustment for implant indication, ejection
      fraction, diabetes, hypertension, and beta-blocker use. Survival was
      significantly shorter in the end-stage renal disease patients, with a median
      survival time of 3.2 +/- 0.6 (SEM) years in the dialysis cohort and 7.4 +/- 0.5
      (SEM) years in those without end-stage renal disease (log rank P = .009). The
      majority of deaths in the end-stage renal disease cohort were due to non-device
      related infection. CONCLUSION: In this cohort, end-stage renal disease was the
      single greatest predictor of ICD therapies for VT/VF. The survival rate was
      significantly shorter than that of ICD recipients without end-stage renal
      disease, suggesting that comorbidities in end-stage renal disease patients
      meeting current implant indications may reduce the survival benefit of ICD
      placement in this population.

PMID- 17018352
TI  - Feasibility and safety of a novel technology for pacing without leads.
AB  - BACKGROUND: Pacemaker lead complications and failures remain clinical problems.
      New devices incorporating three leads are associated with even greater
      limitations. OBJECTIVES: The purpose of this study was to investigate the
      feasibility and safety of a technology enabling cardiac pacing without leads in
      an acute porcine model. METHODS: The system is composed of an ultrasound
      transmitter delivering energy from the chest wall to a receiver-electrode in
      contact with the myocardium that then converts the ultrasound energy to
      electrical energy sufficient to pace. In five feasibility studies, the receiver
      electrodes were attached to the tip of a catheter to facilitate intracardiac
      positioning at pacing sites. In six safety studies (five treatment and one sham),
      ultrasound energy was transmitted to both chest walls, and histopathologic
      examinations were performed to evaluate bioeffects due to ultrasound energy
      transmission. RESULTS: In five feasibility studies, direct and ultrasound
      mediated electrical pacing was demonstrated at 30 sites in the right atrium,
      right ventricle, and left ventricle, at direct electrical pacing outputs of 1.4
      +/- 0.6 V and ultrasound-mediated electrical pacing outputs of 1.8 +/- 0.9 V. The
      mechanical index was 0.6 +/- 0.4 at the receiver site during ultrasound-mediated
      pacing at a depth of 11.2 +/- 2.4 cm from the chest wall. Using two receiver
      electrode catheters, biventricular pacing was demonstrated in all studies. In
      five safety study treatment animals at a similar depth, the peak mechanical index
      was 2.3, and the thermal index was 0.4. Microscopic evaluation revealed no
      evidence of mechanical or thermal bioeffects. CONCLUSION: The feasibility and
      safety of this novel technology for pacing without leads has been demonstrated
      acutely in animals.

PMID- 17018353
TI  - In a footnote, at least.

PMID- 17018354
TI  - Low osmolarity transforms ventricular fibrillation from complex to highly
      organized, with a dominant high-frequency source.
AB  - BACKGROUND: An osmotic challenge activates volume-regulated chloride currents
      (I(Cl,vol)), resulting in depolarization of the resting membrane potential and
      shortening of action potential duration (APD). I(Cl,vol) is activated in
      ischemia/reperfusion, but the effects of osmotic challenges and I(Cl,vol) on
      ventricular fibrillation (VF) are unknown. OBJECTIVES: The purpose of this study
      was to investigate the influence of hypo-osmotic and hypotonic stress and
      I(Cl,vol) activation on VF dynamics. METHODS: Guinea pig hearts were isolated,
      stained with di-4 ANEPPS to optically map action potentials (APs) from epicardium
      using a photodiode array, and perfused with iso-osmotic (low NaCl Ringer plus 45
      mM mannitol) or hypo-osmotic (low NaCl Ringer) solution. RESULTS: Hypo-osmotic
      solution shortened APDs (143 +/- 5 ms --> 115 +/- 10 ms) and increased APD
      gradients between right and left ventricles (21 +/- 7 ms --> 41 +/- 10 ms, n =
      4). In VF induced by burst stimulation, switching to hypo-osmotic solution
      increased VF frequencies (15.3 +/- 1.2 Hz to 28.9 +/- 3.6 Hz, n = 11),
      transforming complex fast Fourier transformation spectra to a single dominant
      high frequency on the left but not the right ventricle. Perfusion with the
      I(Cl,vol) blocker indanyloxyacetic acid-94 (10 muM) reversed organized VF to
      complex VF with lower (13.5 +/- 3.7 Hz in left ventricle) frequencies (n = 8),
      indicating that I(Cl,vol) underlies the changes in VF dynamics. Consistent with
      this interpretation, the levels of ClC-3 channel protein were 27% greater on left
      than right ventricles (n = 10), and computer simulations showed that insertion of
      I(Cl,vol) transformed complex VF to a stable spiral. CONCLUSION: Activation of
      I(Cl,vol) by decreasing osmolarity (45 mOsm) has a major impact on VF dynamics by
      transforming random multiple wavelets to a highly organized VF with a single
      dominant frequency.

PMID- 17018356
TI  - How to deal with data overload.

PMID- 17018355
TI  - Automatic mapping of human atrial fibrillation by template matching.
AB  - BACKGROUND: The high spatiotemporal variation in morphology of fibrillation
      electrograms makes mapping of atrial fibrillation (AF) a difficult and burdensome
      task. OBJECTIVES: The purpose of this study was to evaluate the results of
      automatic detection of fibrillation electrograms by a template matching
      technique. METHODS: During cardiac surgery in 25 patients without a history of
      AF, paroxysms of AF were induced by rapid atrial pacing. A mapping array of 244
      unipolar electrodes (3.6-cm diameter, 2.25-mm interelectrode distance) was
      positioned on the free wall of the right atrium. All fibrillation electrograms
      were correlated with a mathematically constructed library of 128 potentials of
      different duration, RS ratio, and short double components. The moments of maximal
      correlation, coinciding with the negative deflection in the fibrillation
      potentials, were used to create fibrillation maps. RESULTS: In each patient, a
      segment of 18.6 +/- 3.8 seconds of AF was analyzed, resulting in 80 to 130 maps
      per patient. The output of the automatic algorithm was compared with careful
      manual analysis by an experienced investigator. Of the total database of 398,796
      fibrillation potentials, 93.6% +/- 4.2% resulted in a good correlation with one
      of the templates in the library (correlation coefficient >= 0.7). At a
      correlation threshold of 0.6, on average template matching yielded slightly more
      false-positive than false-negative detections (sensitivity 96.6% +/- 2.5%,
      positive predictive value 94.3% +/- 5.4%). The majority of false-positive
      detections were due to electrotonic potentials recorded along the lateral
      boundaries of the fibrillation waves. This led to a slight overlap of
      fibrillation waves but not to false detection of nonexisting wavefronts.
      Undersensing was mainly due to the presence of long double and fractionated
      potentials (2.6%) that were not represented in the template library. Fractionated
      parts in the electrograms were identified by failure of template matching and can
      be analyzed separately. CONCLUSION: Template matching is a useful technique for
      characterizing unipolar fibrillation electrograms and for visualizing the complex
      activation patterns during AF. It allows automatic evaluation of the
      electropathologic substrate of AF on an individual basis.

PMID- 17018357
TI  - Ablation of ventricular tachycardia: neither inside nor out, thus back to
      alcohol.

PMID- 17018358
TI  - What have we learned from mathematical models of defibrillation and postshock
      arrhythmogenesis? Application of bidomain simulations.

PMID- 17018359
TI  - Supraventricular tachycardia with atrioventricular block: what is the mechanism?

PMID- 17018360
TI  - How to perform ablation of the parasympathetic ganglia of the left atrium.

PMID- 17018361
TI  - Dynamic obstruction to coronary sinus access: the Thebesian valve.

PMID- 17018363
TI  - Clinical considerations for the allied professional: translating knowledge about
      amiodarone into education for the patient.

PMID- 17018364
TI  - Re: Vagal denervation and atrial fibrillation inducibility: epicardial fat pad
      ablation does not have long-term effects.

PMID- 17018366
TI  - Recommendations from the Heart Rhythm Society Task Force on Device Performance
      Policies and Guidelines Endorsed by the American College of Cardiology Foundation
      (ACCF) and the American Heart Association (AHA) and the International Coalition
      of Pacing and Electrophysiology Organizations (COPE).

PMID- 17018377
TI  - Glucose 6-phosphate dehydrogenase deficiency: from genotype to phenotype.

PMID- 17018378
TI  - Oral iron chelators: new opportunities and new dilemmas.

PMID- 17018379
TI  - Identification of rare Epstein-Barr virus infected memory B cells and plasma
      cells in non-monomorphic post-transplant lymphoproliferative disorders and the
      signature of viral signaling.
AB  - BACKGROUND AND OBJECTIVES: In early and polymorphic post-transplant
      lymphoproliferative disorders (PTLD) Epstein-Barr virus (EBV), through its
      latency proteins, drives the proliferation of B lymphocytes, a process which in
      immunocompetent individuals leads to the establishment of latently infected
      memory B cells. DESIGN AND METHODS: We analyzed 11 cases, which included early
      and polymorphic PTLD, and 12 controls for latency of EBV infection and their
      antigenic profile. RESULTS: We identified a minority of terminally differentiated
      EBER+ IRTA1+ memory B cells and EBER+ CD138+ PRDM1+ plasma cells in these
      samples. These elements were identified both in PTLD and in tumor-free tonsils
      from post-transplant patients but not in EBV- control tonsils. The expression of
      EBV latency proteins is heterogeneous, and is associated with activation of the
      NF-kB pathway. EBV signaling (through EBNA2, LMP1 and LMP2A) and NF-kB activation
      correlated with upregulation of target proteins: cMYC, JunB, CCL22, TRAF1 and
      IRF4. EBV-infected lymphocytes in early and polymorphic PTLDs represent a mixture
      of latencies II, III and, in at least 1/3 of infected cells, of latency 0.
      INTERPRETATION AND CONCLUSIONS: EBV infection correlates with NF-kB activation,
      with EBV-dependent cell signaling, and lastly, with the presence of EBV-infected
      plasma cells and memory cells.

PMID- 17018380
TI  - Incidence and complete molecular characterization of glucose-6-phosphate
      dehydrogenase deficiency in the Guangxi Zhuang autonomous region of southern
      China: description of four novel mutations.
AB  - BACKGROUND AND OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is
      the most common human metabolic disorder in southern China. We investigated the
      incidence and distribution of mutations, the molecular pathology of affected
      females and the haplotype association with G6PD deficiency in patients from the
      Guangxi region. DESIGN AND METHODS: A population-based molecular analysis
      combining phenotypic screening and genotypic detection using both multiplex
      primer extension/denaturing high performance liquid chromatography assay and DNA
      sequence analysis were performed in a total of 4,704 individuals. RESULTS: The
      mutation frequency of male G6PD-deficient individuals was observed to be 7.43%.
      Twenty-seven genotypes from 361 individuals were found. Statistical analysis
      showed that there were significant differences in both the percentages of
      methemoglobin and the G6PD/6PGD ratio between heterozygote and hemizygote in
      males and between heterozygote and homozygote in females. However, no
      statistically significance was seen between hemizyotes and homozygotes. The
      mutation profile showed that five mutations, G6PD Kaiping(1388A), G6PD
      Canton(1376T), G6PD Gaohe(95G), Chinese-5(1024T)and G6PD Viangchan(817A), are the
      most common in the area, accounting for 85% of the G6PD-deficient alleles. Ten
      rare mutations were detected in approximately 4% of the mutant chromosomes. Four
      novel mutations were found: G6PD Liuzhou(442A), G6PD Nanning(703T), G6PD
      Laibin(1414C,) and G6PD Hechi(202A/817A). In addition, two other rare mutations,
      c.196T-->A and c.202 G-->A, were detected for the first time in Chinese patients.
      A single dominant haplotype (- - + - -) was observed in 94.0% of 182 deficient
      chromosomes. INTERPRETATION AND CONCLUSIONS: Our protocol could be used to extend
      the knowledge of molecular defects of G6PD gene in different geographical areas.

PMID- 17018381
TI  - Myocardial ischemia and right ventricular dysfunction in adult patients with
      sickle cell disease.
AB  - BACKGROUND AND OBJECTIVES: Patients with sickle cell disease (SCD) have multi
      organ manifestations of microvascular disease, though cardiac manifestations have
      been poorly characterized in vivo. This study sought to characterize myocardial
      characteristics in adult patients with SCD. DESIGN AND METHODS: Twenty-two
      consecutive outpatients and 11 age-matched controls underwent magnetic resonance
      imaging to assess myocardial perfusion reserve as well as left and right
      ventricular size and function and myocardial iron. Computed tomography of the
      coronary arteries was performed to assess epicardial coronary stenosis. RESULTS:
      Three of 22 outpatients with clinically stable SCD and no controls had abnormal
      myocardial perfusion reserve limited to the subendocardium, consistent with
      microvascular disease. Coronary arteries were free of disease as detectable by
      computed tomography angiography. Myocardial T2* was normal in all subjects (29 +/
      5 ms, median 29 ms), consistent with absence of cardiac iron deposition despite
      a high prevalence of hepatic iron overload (liver T2* 14 +/- 9 ms, median 12.0
      ms). SCD patients had right ventricular enlargement and dysfunction (right
      ventricular ejection fraction 45 +/- 15 in SCD patients vs. 58 +/- 5% in
      controls, p=0.001) even in the absence of overt pulmonary hypertension.
      INTERPRETATION AND CONCLUSIONS: A subset of adult SCD patients may have
      myocardial ischemia in the absence of infarcted myocardium, myocardial iron
      overload, or coronary artery disease. Right ventricular dysfunction is present in
      stable SCD patients, despite normal resting pulmonary artery pressures. These
      findings could represent under-recognized mechanisms for chest pain and mortality
      in this population, and warrant further investigation in SCD crises.

PMID- 17018382
TI  - Liver expression of hepcidin and other iron genes in two mouse models of beta
      thalassemia.
AB  - BACKGROUND AND OBJECTIVES: Homozygous beta-thalassemia patients may develop iron
      overload even if untransfused, due to inappropriately high intestinal iron
      absorption. Reduction of hepcidin synthesis has been reported both in patients
      and in animal models. We have measured liver hepcidin and other iron gene
      transcripts in two different mouse models of beta-thalassemia at different ages.
      DESIGN AND METHODS: Mice Hbb(th/th), characterized by spontaneous homozygous
      deletion of the major b1 globin gene were studied at 2 and 8 months. Mice
      Hbb(th/3+), characterized by the heterozygous deletion of b1 and b2 globin genes
      were studied at 4 and 10 months. Hematologic data were obtained and iron overload
      estimated by Perls' staining of the liver. Expression of liver hepcidin, Tfr2,
      Hjv, Fpn and Hfe RNA was assessed by real-time polymerase chain reaction. Levels
      of serum cytokines (interleukin-6, IL-1beta, IL-10, granulocyte-macrophage colony
      stimulating factor) levels were assayed by enzyme-linked immunosorbent assay.
      RESULTS: Hemoglobin, hematocrit and mean corpuscular volume were significantly
      reduced in both beta-thalassemia models, more significantly in Hbb(th/3+), which
      have the greater, age-dependent, iron overload. Hepcidin RNA was not increased
      despite iron overload in both strains. Fpn RNA was increased and Tfr2 was
      decreased in older animals. Inflammatory cytokine levels were striking variable
      and unrelated to hepcidin levels. INTERPRETATION AND CONCLUSIONS: Although anemia
      is reported to inhibit hepcidin expression, normal hepcidin synthesis was
      maintained in both thalassemic models studied. However, hepcidin levels were
      inappropriate for the body iron, especially in Hbb(th/3+) 10-month-old animals.
      As we previously reported in wild type mice after parenteral iron overload, Tfr2
      is reduced and Fpn RNA increased in thalassemic mice. Inflammatory cytokines did
      not play a major role in increasing hepcidin levels or in modifying iron
      homeostasis in this study.

PMID- 17018383
TI  - Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent,
      in pediatric patients with beta-thalassemia major.
AB  - BACKGROUND AND OBJECTIVES: Deferasirox (ICL670) is a novel once-daily oral iron
      chelator developed for the treatment of chronic iron overload from blood
      transfusions. This study evaluated the safety and tolerability of deferasirox in
      pediatric patients with transfusion-dependent beta-thalassemia major. Efficacy
      and pharmacokinetic assessments were secondary objectives. DESIGN AND METHODS:
      Forty patients equally stratified into two age groups--children (2 to <12 years)
      and adolescents (12-17 years)--were treated with deferasirox for 48 weeks. All
      received once-daily deferasirox 10 mg/kg/day with modifications allowed after 12
      weeks' treatment. Safety, liver iron concentration (LIC), serum ferritin and
      pharmacokinetics were assessed. RESULTS: Thirty-nine patients completed the
      study. One withdrew due to a skin rash. Adverse events were typical of this
      population, but only four were considered related to the study drug: mild nausea
      (two adolescents) and moderate skin rash (two children). There were no serious
      adverse events related to the study drug. Five patients briefly interrupted
      treatment due to elevated transaminases with no recurrences when treatment
      resumed. The mean deferasirox dose was 11.3 mg/kg/day. Overall LIC increased
      gradually from week 12 as mean daily iron intake was higher than excretion.
      Steady-state plasma levels of deferasirox and its iron complex, Fe
      [deferasirox]2, were comparable between children and adolescents. INTERPRETATION
      AND CONCLUSIONS: Deferasirox was well tolerated by this pediatric population.
      Toxicities known to be associated with other commercially available iron
      chelators were not observed. The dose employed was too low to induce a net
      negative iron balance in this regularly transfused population. Pharmacokinetic
      data support a once-daily dosing regimen based on body weight.

PMID- 17018384
TI  - Type II Glanzmann thrombasthenia in a compound heterozygote for the alpha IIb
      gene. A novel missense mutation in exon 27.
AB  - BACKGROUND AND OBJECTIVES: Glanzmann thrombasthenia is an autosomal recessive
      bleeding disorder characterized by a life-long hemorrhagic tendency and absent or
      severely reduced platelet aggregation in response to agonists, caused by
      quantitative or qualitative abnormalities in the platelet fibrinogen receptor,
      integrin alphaIIb beta3. The aim of this study was to identify the molecular
      genetic defect and determine its functional consequences in a patient with type
      II Glanzmann thrombasthenia. DESIGN AND METHODS: The expression of platelet
      alphaIIb beta3 was determined by flow cytometry and western blotting. Mutations
      were identified by sequencing both cDNA and genomic DNA. Functional
      characterization was assessed by exontrap and transient transfection analysis.
      RESULTS: Flow cytometry and western blot analysis revealed markedly reduced
      levels of platelet alphaIIb beta3, which may account for the residual fibrinogen
      binding detected upon platelet activation. Sequencing of genomic DNA revealed the
      presence of two mutations in the alphaIIb gene: a C1750T transition in the last
      codon of exon 17 changing Arg553 to STOP, and a C2829T transition in exon 27 that
      changes Pro912 to Leu. Sequence analysis of reversely transcribed alphaIIb mRNA
      did not detect cDNA from the C1750T mutant allele, and revealed a significant
      increase of the physiological splicing out of exon 28 in the cDNA carrying the
      C2829T mutation. Transient expression of [912Leu]alphaIIb in CHO-b3 cells showed
      a marked reduction in the rate of surface expression of alphaIIb beta3.
      INTERPRETATION AND CONCLUSIONS: The results suggest that the thrombasthenic
      phenotype is the result of reduced availability of alphaIIb-mRNA, enhanced
      expression of exon 28-deleted transcripts, and defective processing of
      [912Leu]alphaIIb.

PMID- 17018385
TI  - The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG
      on thrombin generation.
AB  - BACKGROUND AND OBJECTIVES: Recent evidence suggests that autoantibodies to tissue
      factor pathway inhibitor (TFPI) and/or antiphospholipid antibodies (aPL) may
      contribute to upregulation of the tissue factor (TF) pathway of blood coagulation
      and the development of thrombotic complications in the antiphospholipid syndrome
      (aPS). The aim of this study was to determine the influence of aPL e.g. anti-beta
      2-glycoprotein-I (anti-beta2GPI) and anti-prothrombin, on in vitro TF-induced
      thrombin generation in the presence and absence of TFPI. DESIGN AND METHODS: IgG
      fractions were collected from subjects with aPL (n=21) and normal controls
      (n=36). Anti-TFPI activity was determined after incubation of IgG isolated from
      control or subject plasma with pooled normal plasma using an amidolytic assay for
      TFPI. The influence of IgG fractions and purified aPL (anti-beta2GPI and anti
      prothrombin) on TF-induced in vitro thrombin generation was determined using a
      chromogenic assay of thrombin activity. RESULTS: Patients with aPL had
      significantly elevated thrombin generation (median [interquartile range])
      compared to normal controls (112.0 [104.0-124.0]% vs 89.9 [85.7-100.9]%,
      respectively; p<0.001). Thrombin generation was significantly correlated with
      anti-TFPI activity in patients with aPL (r(s)=0.452; p=0.039). It was also
      demonstrated that anti-beta2GPI, but not anti-prothrombin IgG antibodies,
      significantly enhanced TF-induced thrombin generation in the presence of TFPI,
      using both purified and patients' samples. INTERPRETATION AND CONCLUSIONS: Our
      findings support the hypothesis that anti-beta2GPI IgG antibodies accelerate
      thrombin generation in the presence of TFPI and may contribute to
      hypercoagulability in patients with aPS.

PMID- 17018386
TI  - High efficacy of combined therapy with pegylated interferon plus ribavirin in
      patients with hemophilia and chronic hepatitis C.
AB  - BACKGROUND AND OBJECTIVES: Eradication of hepatitis C virus (HCV) is particularly
      difficult in patients with hemophilia. In this open, prospective, multicenter
      trial, the efficacy and tolerability of the combination therapy with pegylated
      interferon alpha2b (Peg-IFNalpha2b) plus ribavirin was evaluated in 64 human
      immunodeficiency virus (HIV) seronegative adult hemophiliacs with chronic
      hepatitis C naive to previous antiviral therapy. DESIGN AND METHODS: Peg
      IFNalpha2b was administered at a dose of 1.5 microg/kg subcutaneously once weekly
      plus oral ribavirin 800-1200 mg/day, for 24 weeks to patients with HCV genotypes
      2 and 3 (n=22, 34%) or for 48 weeks to those with genotypes 1 and 4 (n=42, 66%).
      RESULTS: Nine patients (14%) did not complete the study because of non-compliance
      (n=6) or side-effects such as decompensated diabetes, alanine aminotransferase
      flares and severe vomiting (n=3). Twenty-eight patients (44%) required dose
      reduction of either drug. Six months after stopping treatment a sustained
      virological response was achieved in 40 patients (63%), 19 with genotype 2 or 3
      (86%) and 21 with genotype 1 or 4 (50%). A sustained virological response was
      significantly associated with an early virological response (p<0.0001), HCV
      genotypes 2 or 3 (p=0.008), no clinical evidence of cirrhosis (p=0.02) and higher
      pre-treatment serum alanine aminotransferase (p=0.016). INTERPRETATION AND
      CONCLUSIONS: These results show that combination therapy with Peg-IFNalpha2b plus
      ribavirin is highly efficacious in hemophiliacs with chronic hepatitis C.

PMID- 17018387
TI  - Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the
      NOD2/CARD15 gene have been associated with the incidence and the severity of
      acute graft-versus-host disease (GVHD) following allogeneic stem cell
      transplantation (SCT). We hypothesized that the clinical effect of SNP in
      NOD2/CARD15 might be different in patients submitted to T-cell-depleted
      allogeneic SCT, in which donor T cells, the main effectors of GVHD, are
      eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied
      using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted
      SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present
      in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and
      chronic GVHD were not associated with either the donors' or recipients'
      NOD2/CARD15 variants. In contrast, these genetic variants were associated with a
      lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary
      infection was more frequent in the group of patients with NOD2/CARD15 variants.
      In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and
      older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free
      survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious
      effect on clinical outcome in T-cell-depleted allogeneic SCT, which is
      independent of GVHD. These results supports the hypothesis that the detrimental
      effect of NOD2/CARD15 variants in such a transplant setting might be produced by
      an alteration of the innate immune system more than by activation of the adaptive
      immune system.

PMID- 17018388
TI  - Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with
      leukemia following matched-sibling myeloablative allogeneic hematopoietic cell
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Donor cytomegalovirus seropositivity was reported to
      improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT)
      recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV
      specific T cells with minor histocompatibility (H) antigen of recipient cells.
      This study analyzed the role of donor CMV serostatus and HLA-A2 status on
      leukemia outcomes in a large population of HLA-identical HCT recipients. DESIGN
      AND METHODS: Leukemia patients transplanted between 1992 and 2003 at the Fred
      Hutchinson Cancer Research Center were categorized as standard risk [leukemia
      first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high
      risk (advanced disease) patients. Time-to-event analysis was used to evaluate the
      risk of relapse and death associated with HLA-A2 status and donor CMV serostatus.
      RESULTS: In standard risk patients, acute leukemia (p<0.001) and sex mismatch
      (female to male, p=0.004)) independently increased the risk of death, while acute
      leukemia increased the risk of relapse (p<0.001). In high risk patients acute
      leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus
      (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV
      seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had
      no significant effect on mortality or relapse in any HLA group. INTERPRETATION
      AND CONCLUSION: This epidemiological study did not confirm the previously
      reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2
      identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2
      restricted CMV-specific T cells with minor H antigens in a clinical study would
      require knowledge of the patient's minor H antigen genotype. However, because of
      the unbalanced distribution of HLA-A2-restricted minor H antigens in the
      population and their incomplete identification, this question might be more
      appropriately evaluated in in vitro experiments than in a clinical study.

PMID- 17018389
TI  - Human cell engraftment after busulfan or irradiation conditioning of NOD/SCID
      mice.
AB  - Human hematopoietic stem cell (HSC) xenotransplantation in NOD/SCID mice requires
      recipient conditioning, classically achieved by sublethal irradiation.
      Pretreatment with immunosuppressive and alkylating agents has been reported, but
      has not been rigorously tested against standard irradiation protocols. Here, we
      report that treatment of mice with a single dose (35 mg/kg) of Busilvex, an
      injectable form of busulfan, enables equivalent engraftment compared to 3.5 Gy
      irradiation. Mice treated with two doses of 25 mg/kg to reduce busulfan toxicity
      showed increased chimerism. Busulfan conditioning and irradiation resulted in
      comparable sensitivity of HSC detection as evaluated by limiting dilution
      analysis.

PMID- 17018390
TI  - Multi-center validation of the transferability of the magnetic resonance T2*
      technique for the quantification of tissue iron.
AB  - The transferability of the T2* technique for measurement of tissue iron between
      magnetic resonance (MR) scanners is unknown. Heart and liver multi-breath-hold
      T2* sequences were installed on MR scanners at six different sites. T2* was
      assessed locally in five or more patients with thalassemia major (n=39), and
      subjects were re-scanned at the standardization center in London. Inter-center
      reproducibility of T2* in heart and liver was 5.0% and 7.1%, with mean absolute
      differences in T2* of 1.3 ms and 0.45 ms, respectively. The MR multi-breath-hold
      T2* technique for tissue iron quantification is transferable between scanners
      with good reproducibility.

PMID- 17018391
TI  - Clinical and molecular genetic analysis of a family with sitosterolemia and co
      existing erythrocyte and platelet abnormalities.
AB  - We describe the clinical, biochemical and molecular genetic features of a Chinese
      family with sitosterolemia, mainly manifested by hematologic abnormalities. The
      clinical features of three patients were analyzed. Their plasma sterol levels
      were measured, and ABCG5 and ABCG8 genes sequenced to search for the causative
      mutation. The main clinical features of these patients were hemolysis and
      macrothrombocytopenia; they had increased plasma sitosterol but maintained normal
      cholesterol levels. Sequence analysis revealed a novel Gln22X nonsense mutation
      in exon 1 or ABCG5. Our results suggest that blood cells could be a target for
      the toxic effect of plasma phytosterols; the coexisting hematologic abnormalities
      might represent a specific subtype of sitosterolemia.

PMID- 17018392
TI  - Suppression of RANTES in children with Plasmodium falciparum malaria.
AB  - Severe malarial anemia (MA) is the primary manifestation of severe malaria among
      children in areas of holoendemic Plasmodium falciparum transmission. Although
      overproduction of inflammatory-derived cytokines are implicated in the
      immunopathogenesis of severe MA, chemokines such as regulated on activation,
      normal T-cell expressed and secreted (RANTES, CCL5) are largely unexplored in
      childhood malaria. We found that RANTES is decreased during severe MA (p<0.01),
      and associated with suppression of erythropoiesis (p<0.05) and malaria-induced
      thrombocytopenia (p<0.05). These findings suggest that thrombocytopenia may be a
      source of reduced RANTES which may contribute, at least in part, to suppression
      of erythropoiesis in children with malarial anemia.

PMID- 17018393
TI  - The incidence and outcome of myeloid malignancies in 2,112 adult patients in
      southeast England.
AB  - There is a paucity of epidemiological data on chronic myeloproliferative
      disorders and myelodysplastic syndromes (MDS), while subtypes of acute myeloid
      leukemia (AML) are rarely defined. We identified 2,112 adult myeloid malignancies
      in the South Thames area between 1999 and 2000. The incidence (European standard
      population) of AML was 3.00/100,000, that of MDS 3.47/100,000, chronic
      myelomonocytic leukemia (CMML) 0.46/100,000, idiopathic myelofibrosis (IMF)
      0.37/100,000, polycythemia vera (PV) 1.08/100,000, primary thrombocythemia (PT)
      1.65/100,000 and chronic myeloid leukemia (CML) 1.09/100,000. The 3-year survival
      for AML was 15%, MDS 45%, CMML 29%, IMF 48%, PV 80%, PT 81% and CML 50% We
      believe this study reflects the true incidence and outcome of myeloid
      malignancies in South East England.

PMID- 17018394
TI  - Aberrant somatic hypermutation in transformation of follicular lymphoma and
      chronic lymphocytic leukemia to diffuse large B-cell lymphoma.
AB  - The molecular mechanisms involved in histologic transformation of follicular
      lymphoma (FL) and B-chronic lymphocytic leukemia (B-CLL) to diffuse large B-cell
      lymphoma (DLBCL) are heterogeneous and largely unknown. Here we explored whether
      aberrant somatic hypermutation, leading to the acquisition of new mutations in
      PIM-1, PAX-5, RhoH/TTF and c-MYC genes, is involved in transformation from FL or
      B-CLL to DLBCL. Eighteen sequential pairs of FL/DLBCL (n=9) and B-CLL/DLBCL (n=9)
      were investigated. Our findings demonstrate that acquisition of novel mutations
      due to aberrant somatic hypermutation was associated with DLBCL transformation in
      5/9 (55.5%) cases of FL and 2/9 (22.2%) cases of B-CLL.

PMID- 17018395
TI  - Applying the concept of healthcare-associated infections to hematology programs.
AB  - Infection is a leading cause of mortality in hematology. Although data on
      nosocomial infections are available, little is known about events falling into
      the broader category of healthcare-associated infections. Our aim was to evaluate
      the incidence and causes of healthcare-associated infections in hematology
      patients, comparatively with nosocomial infections. Using predefined criteria, we
      classified 223 infectious episodes in 137 patients for their association with
      healthcare and nosocomial occurrence. Of the 223 infectious episodes, 204 (91%)
      were healthcare associated, 94/223 (42%) were also nosocomial, and 9% were
      community-acquired. Healthcare-associated infections should be preferred to
      nosocomial infections--which underestimates half of the healthcare-associated
      infections--as quality indicators for preventive programs.

PMID- 17018396
TI  - Long-term survival in patients with acute leukemia and chronic disseminated
      candidiasis despite minimal antileukemic therapy.
AB  - Infections may require discontinuation of antineoplastic chemotherapy, which, in
      turn, renders patients vulnerable to disease progression or relapse. We
      identified six patients with acute leukemia in whom antineoplastic treatment had
      to be discontinued because of chronic disseminated candidiasis (CDC). However,
      despite minimal antileukemic treatment, all patients remained in complete
      remission. Immunologic mechanisms associated with CDC might have had an
      antileukemic effect.

PMID- 17018397
TI  - Adult acute lymphoblastic leukemia, Burkitt's lymphoma and lymphoblastic lymphoma
      in middle Norway 1985-2004.
AB  - We report a population-based investigation on adult acute precursor B
      lymphoblastic leukemia, Burkitt's lymphoma and T lymphoblastic lymphoma in a
      defined geographic area. The age-adjusted incidence rates for the three
      diagnostic groups were 0.47, 0.16 and 0.2 per 100,000 per year, respectively.
      Clinical characteristics and outcome following treatment are reported.

PMID- 17018398
TI  - Plasma levels of basic fibroblast growth factor and vascular endothelial growth
      factor and their association with IgVH mutation status in patients with B-cell
      chronic lymphocytic leukemia.
AB  - The mutation status of genes encoding the variable region of immunoglobulin heavy
      chains (IgV(H)) is a strong predictor of disease progression and survival in B
      cell chronic lymphocytic leukemia (B-CLL). We investigated whether there is an
      association between the concentration of both vascular endothelial growth factor
      and basic fibroblast growth factor and IgV(H) mutation status in 49 untreated B
      CLL patients.

PMID- 17018399
TI  - Detection of risk-identifying chromosomal abnormalities and genomic profiling by
      multiplex ligation-dependent probe amplification in chronic lymphocytic leukemia.
AB  - We performed genomic profiling using multiplex ligation-dependent probe
      amplification (MLPA) in 54 cases with suspected or advanced chronic lymphocytic
      leukemia (CLL). MLPA detected abnormalities when the percentage of mutated cells
      was greater than approximately 35%. Loss of 9p21 CDNK2A/B was revealed. MLPA is
      an economically attractive, powerful tool in trial-based, centralized risk
      assessment for CLL.

PMID- 17018401
TI  - Antioxidant enzyme inhibitors enhance singlet oxygen-induced cell death in HL-60
      cells.
AB  - Singlet oxygen is a highly reactive form of molecular oxygen that may harm living
      systems by oxidizing critical cellular macromolecules and it also promotes
      deleterious processes such as cell death. The protective role of antioxidant
      enzymes against singlet oxygen-induced oxidative damage in HL-60 cells was
      investigated in control and cells pre-treated with diethyldithiocarbamic acid,
      aminotriazole and oxlalomalate, specific inhibitors of superoxide dismutase,
      catalase and NADP+-dependent isocitrate dehydrogenase, respectively. Upon
      exposure to rose bengal (20 microM)/light (15 min), which generates singlet
      oxygen, to HL-60 cells, the viability was lower and the lipid peroxidation and
      oxidative DNA damage were higher in inhibitor-treated cells as compared to
      control cells. We also observed the significant increase in the endogenous
      production of reactive oxygen species as well as the significant decrease in the
      intracellular GSH level in inhibitor-treated HL-60 cells exposed to singlet
      oxygen. Upon exposure to rose bengal (3 microM)/light (15 min), which induced
      apoptotic cell death, a clear inverse relationship was observed between the
      control and inhibitor-treated HL-60 cells in their susceptibility to apoptosis.
      These results suggest that antioxidant enzymes play an important role in cellular
      defense against singlet oxygen-induced cell death including necrosis and
      apoptosis.

PMID- 17018402
TI  - Gas-phase deposition of polychlorinated biphenyls (PCBs) to a water surface
      sampler.
AB  - In this study a water surface sampler (WSS) was utilized to directly measure gas
      phase deposition of polychlorinated biphenyls (PCBs). The measured gas phase PCB
      fluxes averaged about 880 +/- 660 ngm(-2)d(-1), which was higher than the fluxes
      calculated using simultaneously measured air and water concentrations for natural
      surface waters. These large fluxes were due to fact that the measured fluxes were
      only in the absorption direction since deposited PCBs were continuously removed
      from the system using an XAD column resulting in the maximum possible flux rate
      from the air to the WSS water. Ambient air PCBs were also sampled simultaneously
      with a modified high volume sampler. The gas phase PCB concentrations changed
      between 0.90 and 4.46 ngm(-3) (2.18 +/- 1.16 ngm(-3)). The mass transfer
      coefficients (MTCs), calculated by dividing the fluxes by the gas phase
      concentrations was 0.40 +/- 0.36 cms(-1). The average MTC was comparable with
      those calculated using a similar configuration of a WSS.

PMID- 17018403
TI  - Multipathway polycyclic aromatic hydrocarbon and pyrene exposure among children
      living in Campania (Italy).
AB  - Multipathway exposure to polycyclic aromatic hydrocarbons (PAHs) and Pyrene (Py)
      was studied among children ages 7-9 living in two areas of the Campania Region
      (South-Italy) classified as urban and rural. During five consecutive days PAHs
      and Py were detected in air samples from outdoors, indoors (school and home),
      individuals at inhalatory levels, and in food and beverages (defined as food)
      consumed daily by each child. 1-hydroxypyrene (1-OHP) was detected in children's
      urine. Gender, weight and height of each subject were recorded, and the personal
      Body Mass Index (BMI) calculated. The type of home heating, the presence of
      smokers and the number of cigarettes smoked at home was determined. Total PAH and
      Py median concentrations in outdoor air from urban areas were 1.70 ng m(-3) and
      0.19 ng m(-3), respectively while in rural areas they were 1.10 ng m(-3) and 0.14
      ng m(-3). Indoor air total PAH and Py median concentrations were 2.50 ng m(-3)
      and 0.15 ng m(-3), respectively for urban areas, and 4.10 ng m(-3) and 0.15 ng m(
      3) for rural areas. In food the total PAH and Py median levels were 10.44 and
      0.81 microg kg(-1) in urban areas and 18.90 and 0.90 microg kg(-1) in rural
      areas. The median urinary levels of 1-OHP for urban and rural children were 0.07
      and 0.06 micromol/mol creat., respectively. From these data, food appears to be
      the most relevant source of exposure to PAHs and Py. The Py intake from single
      (food or air) or total (food and air) pathways did not significantly correlate
      with the urinary 1-OHP excreted daily for each child during all 5 days of
      observation.

PMID- 17018404
TI  - Comparative phosphorus sorption by marine sediments and agricultural soils in a
      tropical environment.
AB  - The influence of soil phosphorus (P) sources on P sorption characteristics of
      marine sediments was investigated for Pearl Harbor and off shore Molokai in
      Hawaii. Estuary sediments were sampled in seven locations; these represented
      different soils and on-shore activities. The soil samples included nine major
      soils that contributed sediment to the Harbor and coastal sediments near the
      island of Molokai. Sediment and soil samples were equilibrated for 6 days in 0.01
      M CaCl(2) solution and synthetic seawater containing differing amounts of P.
      Phosphorus sorption curves were constructed. The equilibrated solution P, with no
      P added, ranged from 0.01 to 0.2 mg L(-1); P sorption by sediments at standard
      solution concentration 0.2 mg L(-1), ranged from 0 to 230 mg kg(-1). Sediment P
      sorption corresponded closely with soil sorption characteristics. Soils
      contributing sediments to the west reach of Pearl Harbor are highly weathered
      Oxisols with high standard P sorption values while those in the southeast of the
      Harbor were Vertisols and Mollisols which sorb little P. The influence of source
      materials on sediment P sorption was also observed for off-shore sediments near
      Molokai. Sediments serve as both source and sink for P in Pearl Harbor and in
      this role can be a stabilizing influence on P concentration in the water column.
      Phosphorus sorption curves in conjunction with water quality data can help to
      understand P dynamics between sediments and the water column and help evaluate
      concerns about P loading to a water body. For Pearl Harbor, solution P in
      equilibrium with sediments from the Lochs was 0.021 mg L(-1); a value unlikely to
      produce an algal bloom. (Measured total P in the water columns (mean) was
      0.060.).

PMID- 17018405
TI  - Some chemical contaminant of surface sediments at the Baltic Sea coastal region
      with special emphasis on androgenic and anti-androgenic compounds.
AB  - Androgenic and anti-androgenic compounds including p,p'-DDE, Diuron, Linuron,
      Fenarimol, Vinclozolin, 1-(3,4-dichlorophenyl) urea (DCPU), 1-(3,4
      dichlorophenyl)-3-methylurea, (DCPMU), tributyltin (TBT) and triphenyltin (TPT)
      and their metabolites (DBT, MBT, DPT, MPT) as well as metallic elements (Ni, Cu,
      Zn, As, Cd, Pb, Co, Tl, Cr, Fe, Mn, Al, K, Mg, Na, Ca, Ba, Ti, Sn), PAHs (16
      indicator compounds), DDTs and PCBs have been quantified in top layer (0-10 cm)
      of up to 37 surface sediment samples collected from several sites in costal zone
      of the Gulf of Gdansk, an inland freshwater area of Brdyujscie in Poland and the
      tidal flats of the Norderney Island, Wadden Sea in 2002-2003. These sites
      differed in the degree of anthropogenic activities, including chemical pollution
      and related impact on biota. Especially in sediments near shipyards, ship repair
      facilities, harbours, other industrial activities or close to municipal sewage
      treatment plant outlets butyltins, PAHs and some metallic elements were found at
      high concentrations. Diuron, Linuron and DCPMU were detected at a few sites,
      Fenarimol only once, while Vinclozolin and DCPU were not detected. DDT
      concentrations in the sediments from the Gdansk and Gdynia region of the Gulf
      show a stepwise decrease following the ban for production and use, while
      diffusion of PCBs at some industrial sites seems to continue. Elevated PAH
      concentrations in sediments seem to be mainly due to pyrogenic and less to mixed
      pyrogenic and petrogenic sources, while for a few sites rather petrogenic sources
      dominated. The reference sites in the Norderney Island, Wadden Sea showed similar
      or slightly higher loads of DDTs, BTs, PAHs, PCBs and metallic elements when
      compared to sediments from the least contaminated sites in the coastal Gulf of
      Gdansk area, while phenyltins were not detected at both spatially distant
      European areas.

PMID- 17018406
TI  - Effect of hypochloride on microbial ecology of bulking and foaming activated
      sludge treatment for tannery wastewater.
AB  - This study investigates the effect of hypochloride application for controlling
      bulking and foaming on the microbial ecology of an activated sludge system
      treating tannery wastewater. Detailed characterization of the wastewater
      treatment influent and effluent is also reported for the study period. During the
      study, bulking and foaming are first monitored with a sudden burst in the sludge
      volume index over 250 mL g(-1), creating a significant deterioration of the
      effluent quality. The corresponding upset in the microbial ecology is the
      combined excessive proliferation of M. parvicella, N. limicola II and Gordona
      (Nocardia) spp., but mainly triggered by Gordona contamination of the floc
      structure and the rapid outward growth of this filamentous microorganism
      extending to adjacent flocs. Chlorine application at an average rate of 3 g Cl(
      1)(kg MLSS.day)(-1) for 12 days provide an effective solution for bulking and
      foaming, restoring the effluent quality. It destroys filamentous texture between
      the flocs, leaving only a lot of loose and chopped filament fragments and,
      totally removes the Gordona spp. from solution which retrieves back into the
      flocs. Therefore, chlorine remediation of bulking and foaming, although
      temporarily effective, is only superficial as the Gordona seeding inside the floc
      remains intact and potentially available for excessive growth in the next
      favorable conditions.

PMID- 17018407
TI  - Performance assessment of major wastewater treatment plants (WWTPs) in the state
      of Georgia.
AB  - A survey was conducted to report on the types and efficiencies of various
      treatment technologies being used at major wastewater treatment plants (WWTPs) in
      the state of Georgia. Twenty-four, full-scale wastewater treatment facilities
      with a design capacity of 37,850 m(3) d(-1) (10 Mg d(-1)) or greater were
      evaluated. One year of operating data for the 2003 calendar year was obtained
      from discharge monitoring reports (DMRs) provided by the Georgia Environmental
      Protection Division (EPD) in Atlanta. Additional information was gathered about
      facility operations and the types of chemicals used through review of EPD files
      and interviews with plant personnel. Data evaluated were: influent and effluent
      five-day Biochemical Oxygen Demand (BOD(5)), influent and effluent total
      suspended solids (TSS), effluent ammonia nitrogen (NH(3)-N), and effluent Total
      Phosphorus (TP). Effluent requirements for BOD(5) or five-day carbonaceous
      biochemical oxygen demand (CBOD(5)), TSS, ammonia nitrogen (NH(3)-N), TP, and
      dissolved oxygen (DO) vary by facility. Time series plots showing average
      effluent parameter concentrations versus month indicate the effectiveness of
      wastewater treatment as a function of type of treatment technology and
      temperature. Probability plots highlight the relationship between various
      effluent parameters and associated treatment technology. Fourteen facilities met
      all permit requirements, whereas ten of the facilities reported violations with
      regard to flow and/or effluent parameters. Chemicals utilized, design capacity,
      and monthly effluent concentrations are presented in this study.

PMID- 17018408
TI  - An investigation of wide-angle dense-medium cycloning for the recovery of metal
      and aggregate from fine slag.
AB  - An investigation was carried out to evaluate the feasibility of using wide-angle
      dense-medium cycloning to process a fine (-600 microm) stainless-steel slag. The
      slag was characterized by size and density using a combination of sieving and
      pycnometer measurements. Separation testing was carried out using a laboratory
      dense-medium cyclone to concentrate the stainless-steel fraction and produce a
      low-metal aggregate material. The effects of cyclone geometry (cone angle,
      underflow diameter, overflow diameter, cylinder length, and vortex finder length)
      and medium density on cyclone performance were evaluated. A Plackett-Burman
      statistical design was used to determine the significant variables as related to
      recovery and purity of the metal and aggregate products. Based on these results,
      full-factorial designs were performed at two different medium densities.
      Regression models relating the significant variables to product recovery and
      purity were developed for both the metal and aggregate fractions.

PMID- 17018409
TI  - Constructed tropical wetlands with integrated submergent-emergent plants for
      sustainable water quality management.
AB  - Improvement of primary effluent quality by using an integrated system of emergent
      plants (Scirpus grossus in the leading subsurface flow arrangement) and
      submergent plants (Hydrilla verticillata in a subsequent channel) was
      investigated. The primary effluent was drawn from a septic tank treating domestic
      sewage from a student dormitory at the University of Peradeniya, Sri Lanka.
      Influent and effluent samples were collected once every 2 weeks from May 2004
      through July 2005 and analyzed to determine water quality parameters. Both the
      emergent and submergent plants were harvested at predetermined intervals. The
      results suggested that harvesting prolonged the usefulness of the system and the
      generation of a renewable biomass with potential economic value. The mean overall
      pollutant removal efficiencies of the integrated emergent and submergent plant
      system were biological oxygen demand (BOD5), 65.7%; chemical oxygen demand (COD),
      40.8%; ammonium (NH4+-N), 74.8%; nitrate (NO3--N), 38.8%; phosphate (PO43-),
      61.2%; total suspended solids (TSS), 65.8%; and fecal coliforms, 94.8%. The
      submergent plant subsystem improved removal of nutrients that survived the
      emergent subsystem operated at low hydraulic retention times. The significant
      improvement in effluent quality following treatment by the submergent plant
      system indicates the value of incorporating such plants in wetland systems.

PMID- 17018410
TI  - HRGC/HRMS analysis of chloronaphthalenes in several batches of Halowax 1000,
      1001, 1013, 1014 and 1099.
AB  - Chloronaphthalene (CN) congeners and homologue groups have been quantified in up
      to three batches of several types of technical CN formulations of the Halowax
      series (Halowax 1031, 1000, 1001, 1013, 1014 and 1099), to elucidate possible
      batch-to-batch compositional variations. Using isotope dilution and HRGC/HRMS a
      relatively large variation in CN congeners and homologues composition among the
      batches of particular types of the Halowax formulations could be noted, and also
      when compared to the composition declared by the manufacturer. Depending on the
      type of the Halowax formulation and its batch in total up to 54 peaks from
      chloronaphthalenes (Agilent Ultra 2 liquid phase), which represented 70 of 75 CN
      congeners theoretically possible, could be found in these mixtures. These
      congeners represented all CN homologue groups from mono- to octaCN but some co
      eluted. A co-eluting congeners were such as: 1,4-/1,6- (nos. 5/7), 1,5-/2,7-
      (nos. 6/12), 2,6-1,7- (nos. 11/8) of diCNs; 1,3,6-/1,3,5- (nos. 20/19), 1,3,7
      /1,4,6- (nos. 23/24), 1,6,7-/2,3,6- (nos. 25/26) of triCNs; 1,2,5,7-/1,2,4,6
      /1,2,4,7- (nos. 37/33/34), 1,3,6,8-/1,2,5,6- (nos. 45/36), 1,2,3,5-/1,3,5,8-
      (nos. 28/43), 1,2,3,4-/1,2,3,7- (nos. 27/30), 1,2,5,8-/1,2,6,8- (nos. 38/40) of
      tetraCNs; 1,2,3,5,7-/1,2,4,6,7- (nos. 52/60), 1,2,3,5,8-/1,2,3,6,8- (nos. 53/55)
      of pentaCNs; 1,2,3,4,6,7-/1,2,3,5,6,7- (nos. 66/67), 1,2,3,4,5,7-/1,2,3,5,6,8-
      (64/68) and 1,2,4,5,6,8-/1,2,4,5,7,8- (nos. 71/72) of hexaCNs. Absent in the
      Halowaxes were CN congeners such as 1,3,8-triCN (no. 22) (<0.0002 mg/g), 1,3,6,7
      tetraCN (no. 44), 1,2,3,6-TetraCN (no. 29), 1,2,3,6,7-pentaCN (no. 54) and
      1,2,3,6,7,8-hexaCN (no. 70) (<0.0005 mg/g).

PMID- 17018412
TI  - Electrodegradation of methylene blue dye in water and wastewater using lead
      oxide/titanium modified electrode.
AB  - A modified electrode was prepared by the electrodeposition of a lead oxide layer
      on a titanium substrate. This electrode was used as an anode for electrocatalytic
      oxidation process of dyestuff in aqueous solution. The modified electrode was
      used for electrochemical degradation of methylene blue dye. The results of the
      electrocatalytic oxidation process of the dyestuff solutions were expressed in
      terms of the remaining dye concentration and chemical oxygen demand (COD) values.
      Different operating conditions and factors that affected the treatment process
      including current density, pH, initial dye concentration, conductive electrolyte
      and time of electrolysis were studied. The optimum operating conditions for the
      dye and modified electrode were investigated. This has resulted in complete
      removal of the dye and COD. The optimum conditions were applied to the treatment
      of methylene blue dye in real wastewater solutions. These results indicate that
      the suggested modified electrode was highly efficient in the treatment of
      effluents containing methylene blue dye with very slight effect of matrix. This
      electrochemical system is robust in structure and simple in operation. It has the
      potential to be developed as a feasible and an effective wastewater treatment
      process.

PMID- 17018411
TI  - An evaluation of sources of nitrogen in shallow groundwater using (15)N abundance
      technique.
AB  - A (15)N abundance technique was employed to identify the source of NO(3)-N in
      groundwater under three commercial citrus production sites in central Florida.
      Water samples were collected from 0 to 300 and 300 to 600 cm depths in the
      surficial aquifer and analyzed for NO(3)-N and delta N-15 (delta (15)N).
      Groundwater samples were also collected in a residential area adjacent to one of
      the citrus groves and analyzed for NO(3)-N and delta (15)N. The delta (15)N
      values were in the range of (+)1 to (+)10% in both depths underneath the citrus
      groves. The range of delta (15)N measured in this study represents the range
      expected for groundwater that was impacted by NO(3)-N originated from
      mineralization of organic N from the soil as well as from the crop residue. There
      are occasional high delta (15)N values which are indicative of the effects of
      NH(3) volatilization losses of applied fertilizer N. The range of delta (15)N
      values for groundwater samples collected from the residential area adjacent to
      the citrus groves was very similar to that from the groundwater underneath the
      citrus groves. Thus, the source of NO(3)-N that impacted the groundwater under
      the citrus groves also impacted the groundwater in the adjacent residential area.

PMID- 17018413
TI  - Removal kinetics and mechanism for crystal violet uptake by surfactant-modified
      alumina.
AB  - Sodium dodecyl sulfate (SDS), an anionic surfactant (AS) was used for the surface
      modification of neutral alumina. Micelle-like structures are formed on the
      surface of alumina, which was used for the removal of crystal violet (CV), a well
      known cationic dye from aquatic environment. This process is called
      adsolubilization. The surfactant-modified alumina (SMA) was found to be very
      efficient showing >99% CV removal from a 200 ppm CV bearing solution with only 6
      g/L of adsorbent dose. The kinetic studies showed that 60 minutes' shaking time
      was sufficient to achieve the equilibrium. The reaction kinetics data were
      analysed using four reaction kinetic models, viz., first-order reaction model,
      pseudo-first-order reaction model, second-order reaction model and pseudo-second
      order reaction model, and it was found that the removal of CV followed the pseudo
      second order reaction model. It was found that neither film diffusion nor pore
      diffusion was rate limiting for this process. Isotherm studies showed that
      Langmuir isotherm fitted more accurately compared to Freundlich isotherm. To test
      whether the removal of CV was possible from real water using SMA, the experiments
      were conducted using CV spiked distilled water and synthetic wastewater. It was
      interesting to note that the removal efficiency was better for wastewater as
      compared to that of distilled water.

PMID- 17018414
TI  - Ozonation of dyes and textile wastewater in a rotating packed bed.
AB  - This study investigates the ozonation of Reactive Red 120 and Acid Red 299 dyes
      in the synthesized solution and textile wastewater by using a rotating packed
      bed. The decomposition rate of Reactive Red 120 and Acid Red 299 dyes via
      ozonation can be described by the pseudo-first-order kinetics. Ozonation of
      Reactive Red 120 exhibited the higher mineralization rate compared with that of
      Acid Red 299. The biodegradability of the two dyes could be significantly
      promoted during the ozonation. The BOD5/TOC (5-day biological oxygen demand/total
      organic carbons) ratios of the ozonated Reactive Red 120 and Acid Red 299
      solutions would increase and have the maximum values. Moreover, the oxidized
      textile wastewater revealed the fast decolorization and moderate COD (chemical
      oxidation demand) removal rates. The optimal ADMI (American Dye Manufactures
      Institute) and COD removal of the textile wastewater were 93% and 37% in 30
      minutes ozonation time, respectively. The performance evaluation of ozonation in
      the rotating packed bed indicated that the higher water flow rate, gas ozone
      concentration and rotational rotating speed would increase the efficiency of
      mineralization.

PMID- 17018415
TI  - Using compost from urban solid waste to prevent erosion in road embankments.
AB  - This paper describes how compost, a by-product generated by solid waste treatment
      plants, can be usefully applied to road embankments to prevent erosion. Our study
      analyzed this process in terms of the following variables: (1) location and
      orientation; (2) embankment slope; (3) soil and compost characteristics; (4)
      compost dosage; (5) vegetation species; (6) plot dimensions; and (7) planting
      method. The results obtained focus on the vegetation survival rate, plant growth
      and germination; colonization of other species; cover crop for plots; and erosion
      estimation. It was found that when greater quantities of compost were added to
      embankments, soil loss was decreased. The addition of this material also produced
      a marked increase in plant growth, the survival rate of manually planted
      vegetation, the colonization of other species, as well as the cover crop.
      However, we observed that compost seemed to hinder the germination of hydroseeded
      species, whereas colonizing plants germinated more quickly. The side slope was
      not found to be a significant factor for manually planted species, but turned out
      to be crucial for hydroseeded varieties.

PMID- 17018416
TI  - Sodium ferrate (IV) and sodium hypochlorite in disinfection of biologically
      treated effluents. Ammonium nitrogen protection against THMs and HAAs.
AB  - The work described in this paper presents an evaluation of disinfection by
      products generation in four different biological treatment plant effluents,
      making use of sodium hypochlorite and sodium ferrate (IV) at varying
      concentration and reaction time. Correlations between pH, chemical oxygen demand,
      total organic carbon, ammonium nitrogen, combined chlorine and trihalomethanes
      (THMs) and haloacetic acids (HAAs) were carried out. Disinfection by-products
      generation presented a direct relation with concentration and sodium hypochlorite
      reaction time. For the highest hypochlorite concentration employed (20 mg L(-1))
      and highest reaction time (168 h), the THMs total did not exceed 312.96 microg L(
      1), a value that lies below the Brazilian emission standard for treated effluents
      (1 mg L(-1) of chloroform). The THMs presented an inverse correlation with
      ammonium nitrogen, when inverse (R(2) = 0.646; P < 0.001) and exponential (R(2) =
      0.707; P < 0.001) function were used. As per HAAs this same relation was observed
      for logarithmic (R(2) = 0.0397 P < 0.001) and exponential (R(2) = 0.508; P <
      0.001) functions. The more nitrified the effluent, the bigger the chlorinated
      disinfection by-product generation. The disinfectant sodium ferrate (IV) does not
      lead to halogenated by-product formation.

PMID- 17018417
TI  - The effects of jet cavitation on the growth of Microcystis aeruginosa.
AB  - Different operating factors of jet cavitation method affecting one of
      cyanobacterial's (Microcystis aeruginosa) growths were investigated. The
      inhibition on M. aeruginosa growth by the jet cavitation method depended strongly
      on the hydraulic characteristics of cavitation tube, inlet pressure, cavitation
      number, light and different algae concentrations. The inhibitive efficiency of
      64.58% in field water sample was obtained by this method. Moreover, the
      ultrastructural changes of M. aeruginosa before and after treatment were observed
      by the transmission electron microscope (TEM). The changes of UV-Visible spectra
      further demonstrated the inhibitive behaviors of jet cavitation on the growth of
      M. aeruginosa. The experimental results showed that jet cavitation method was a
      potential physical technology that could effectively inhibit the growth of M.
      aeruginosa.

PMID- 17018418
TI  - Determination of electron donors by comparing reaction rates for in situ
      bioremediation of nitrate-contaminated groundwater.
AB  - Groundwater contaminated by nitrates occurs frequently. In this research,
      fumarate, acetate, formate, lactate, propionate, ethanol, and methane were
      evaluated as a potential electron donor and carbon source by comparing the
      denitrification rate for the in situ bioremediation of nitrate contaminated
      groundwater. The denitrification rate for each substance was the quickest in the
      order of: fumarate > hydrogen > formate/Lactate > ethanol > propionate > methanol
      > acetate. Microcosm studies were performed with fumarates and acetates. When
      fumarates were used as a substrate, nitrates were removed completely at a rate of
      0.66 mmol/day, while the conversion rate from nitrate to nitrogen gas and other
      by-products was 87%. For the microcosm test, 42 mg of fumarates were needed to
      remove 30 mg of NO(3)--N/L. When using acetate as a sole carbon source, 31% of
      nitrates were removed during the initial adjustment period. Among the removed
      fractions, however, 83% of the nitrates were removed by the cell growth. Overall,
      the nitrate removal rate was 0.37 mmol/day when acetate was used as a sole carbon
      source. The acetate showed longer lag time before denitrification occurred, which
      implied that fumarate would have been a better carbon source compared to acetate
      as more amounts were utilized for nitrate removal than cell growth.

PMID- 17018419
TI  - Effects of mixing low amounts of orange peel (Citrus reticulata) with hydrocarbon
      contaminated soil in solid culture to promote remediation.
AB  - The effect of mixing low amounts of orange peel (Citrus reticulata) with a soil
      contaminated with hydrocarbons (58,000 mg kg(-1) soil) for promoting the soil
      remediation in solid culture was studied. The experimental design was established
      in solid culture at soil/orange (Citrus reticulata) peel ratios of 100:0, 98:2,
      96:4, 94:6 and 92:8, at 30% humidity and a C:N:P ratio of 100:10:1, for 15, 60
      and 90 days, respectively. The total petroleum hydrocarbons (TPHs) decreased
      significantly (69%) after 15 days in the treatment with a soil to orange peel
      ratio of 92:8. Furthermore, in this treatment bacterial counts increased from 17
      to 20 ln CFU (2.6 x 10(6) to 5 x 10(8)), while the fungal count was 11 ln CFU
      (6.5 x 10(4)) at initial and final time of treatment. An increase in microbial
      respiration activity and TPH removal (69%) was observed at other soil/orange peel
      ratios after 60 days when moisture content and nutrients were adjusted; however,
      N and P were not consumed at a great extent.

PMID- 17018420
TI  - Coagulation and disinfection efficiency of an electrochemically prepared dual
      function reagent in municipal wastewater.
AB  - A novel dual-function chemical reagent was successfully prepared by electrolysis
      process. With high content of Al13 species and active chlorine, the
      electrochemically prepared polyaluminum chlorine (E-PACl) as the dual-function
      chemical reagent presented the integrated properties of coagulation and
      disinfection in water treatment. The results obtained from jar tests in municipal
      wastewater and hydrolyzed Al (III) speciation distribution characterization
      confirmed that the Al13 species was the most effective polymeric Al species in
      PACl responsible for coagulation. The solid-state 27Al NMR spectra for
      precipitates revealed that the precipitates structure formed from Al coagulants
      with various pre-hydrolysis degrees were significantly different, and proved that
      the preformed Al13 polymer is quite stable during the coagulation process. E-PACl
      performed well on both particulate and organic matter removals in municipal
      wastewater treatment. The higher the degree of pre-hydrolysis, the lower the
      efficiency of the coagulant removed phosphorus from water. The active chlorine in
      E-PACl was an effective disinfectant to inactivate fecal coliforms. When dosed 24
      mg Al/L E-PACl, effective coagulation and disinfection in municipal wastewater
      could be achieved simultaneously. E-PACl may have a great potential to domestic
      use and small treatment plants for municipal wastewater reuse.

PMID- 17018421
TI  - Human health effects from chronic arsenic poisoning--a review.
AB  - The ill effects of human exposure to arsenic (As) have recently been reevaluated
      by government agencies around the world. This has lead to a lowering of As
      guidelines in drinking water, with Canada decreasing the maximum allowable level
      from 50 to 25 microg/L and the U.S. from 50 to 10 microg/L. Canada is currently
      contemplating a further decrease to 5 microg/L. The reason for these regulatory
      changes is the realization that As can cause deleterious effects at lower
      concentrations than was previously thought. There is a strong relationship
      between chronic ingestion of As and deleterious human health effects and here we
      provide an overview of some of the major effects documented in the scientific
      literature. As regulatory levels of As have been decreased, an increasing number
      of water supplies will now require removal of As before the water can be used for
      human consumption. While As exposure can occur from food, air and water, all
      major chronic As poisonings have stemmed from water and this is usually the
      predominant exposure route. Exposure to As leads to an accumulation of As in
      tissues such as skin, hair and nails, resulting in various clinical symptoms such
      as hyperpigmentation and keratosis. There is also an increased risk of skin,
      internal organ, and lung cancers. Cardiovascular disease and neuropathy have also
      been linked to As consumption. Verbal IQ and long term memory can also be
      affected, and As can suppress hormone regulation and hormone mediated gene
      transcription. Increases in fetal loss and premature delivery, and decreased
      birth weights of infants, can occur even at low (<10 microg/L) exposure levels.
      Malnourished people have been shown to be more predisposed to As-related skin
      lesions. A large percentage of the population (30-40%) that is using As
      contaminated drinking water can have elevated As levels in urine, hair and nails,
      while showing no noticeable clinical symptoms, such as skin lesions. It is
      therefore important to carry out clinical tests of As exposure. Factors combining
      to increase/decrease the ill effects of As include duration and magnitude of As
      exposure, source of As exposure, nutrition, age and general health status.
      Analytical determinations of As poisoning can be made by examining As levels in
      urine, hair and toenails. Communities and individuals relying on groundwater
      sources for drinking water need to measure As levels to ensure that their
      supplies are safe. Communities with water As levels greater than 5 microg/L
      should consider a program to document As levels in the population.

PMID- 17018422
TI  - Healing substrates with mobile, particle-filled microcapsules: designing a
      'repair and go' system.
AB  - We model the rolling motion of a fluid-driven, particle-filled microcapsule along
      a heterogeneous, adhesive substrate to determine how the release of the
      encapsulated nanoparticles can be harnessed to repair damage on the underlying
      surface. We integrate the lattice Boltzmann model for hydrodynamics and the
      lattice spring model for the micromechanics of elastic solids to capture the
      interactions between the elastic shell of the microcapsule and the surrounding
      fluids. A Brownian dynamics model is used to simulate the release of
      nanoparticles from the capsule and their diffusion into the surrounding solution.
      We focus on a substrate that contains a damaged region (e.g. a crack or eroded
      surface coating), which prevents the otherwise mobile capsule from rolling along
      the surface. We isolate conditions where nanoparticles released from the arrested
      capsule can repair the damage and thereby enable the capsules to again move along
      the substrate. Through these studies, we establish guidelines for designing
      particle-filled microcapsules that perform a 'repair and go' function and thus,
      can be utilized to repair damage in microchannels and microfluidic devices.

PMID- 17018423
TI  - Concentration dependence of vibrational properties of bioprotectant/water
      mixtures by inelastic neutron scattering.
AB  - Neutron scattering has been demonstrated to be a powerful tool for characterizing
      the structure and dynamics of biological molecules and for investigating the
      physical and chemical mechanisms of biophysical processes. The aim of the present
      work is to investigate by inelastic neutron scattering (INS) the vibrational
      behaviour of a class of bioprotectant systems, such as homologous disaccharides,
      trehalose, maltose and sucrose, in water mixtures. INS measurements have been
      performed on trehalose/H2O, maltose/H2O and sucrose/H2O mixtures at very low
      temperature as a function of concentration by using the thermal original
      spectrometer with cylindrical analyzers (TOSCA) spectrometer at the ISIS Facility
      (DRAL, UK). The findings allow the analyses of the vibrational features of the
      INS spectra in order to study the effect of disaccharides on the H2O hydrogen
      bonded tetrahedral network. The obtained neutron scattering findings point out
      that disaccharides, and in particular trehalose, have a destructuring effect on
      the water tetrahedral network, as emphasized by the analysis of the librational
      modes region from 50 to 130 meV energy transfer. On the other hand, the analysis
      of the bending modes region (130-225 meV) shows a locally ordered structure in
      the disaccharide/H2O mixtures.Finally, the observed experimental evidences are
      linked to the different bioprotective effectiveness of disaccharides as a
      function of concentration.

PMID- 17018424
TI  - Imaging and interventional radiological treatment of hemoptysis.
AB  - Hemoptysis is coughing up blood originating from the lower respiratory tract.
      There are multiple causes of hemoptysis, from airway diseases, parenchymal
      diseases, cardiovascular diseases, and other causes. Hemoptysis may cease
      temporarily, but a possible life-threatening condition may still be present,
      requiring complete evaluation and probably treatment. Massive hemoptysis (>300 ml
      blood in 24 hours) seldom occurs but has high mortality. Diagnostic examinations
      include patient history, physical examination, bronchoscopy, laboratory tests,
      chest X-ray, computed tomography (CT) of the chest, pulmonary angiography,
      aortography, and angiography of the bronchials and other thoracic systemic
      arteries. Bronchoscopy together with clinical and radiological examinations
      indicates from which part of the lung the bleeding is occurring, yet the cause of
      hemoptysis cannot be determined in 20-30% of cases. One of the therapeutic
      measurements may be embolization of the bleeding vessel such as in pulmonary
      arteriovenous malformations or in bronchial or other systemic arterial branches
      supplying the bleeding lung segment. Systemic bronchial and non-bronchial
      collateral artery anatomy is very complex and variable, and it may be difficult
      to recognize how the systemic arteries or pulmonary arteries may be involved as a
      source of bleeding. Interventional treatments are effective and safe therapeutic
      methods which reduce the need for acute thoracic surgery. Embolization may be
      life saving, or it may postpone surgery and, in some situations, should be the
      treatment of choice.

PMID- 17018425
TI  - Comparison of methods for chemical-compound affinity prediction.
AB  - The selection of effective features from various descriptors of chemical
      compounds and the exploitation of the most appropriate classifier is a momentous
      issue in improving overall accuracies of virtual screening of chemical compounds.
      In this article, the performance of various feature-selection methods and various
      classifiers of chemical compound-protein binding affinities are compared by using
      six series of compounds: cytochrome P450 2C9 inhibitors, multi-drug-resistance
      reversal compounds, estrogen receptor ligands, inhibitors of human ether-a-go-go
      related genes, and ligands of serotonin receptor 5HT1A and 5HT2A. As a result, it
      was found that the genetic algorithm was superior to the other feature-selection
      methods, and its combination with Random Forests and Adaboosts or Baggings gave
      almost the same performance as support-vector machines and was superior to the
      other classifiers. The precision and recall of these methods were almost the same
      or ascendant to those of previous work. The automatically selected descriptors
      for each protein-compound affinity prediction were plausible and would be
      informative to interpret the resulting model.

PMID- 17018427
TI  - Sexual dichroism and pigment localization in the wing scales of Pieris rapae
      butterflies.
AB  - The beads in the wing scales of pierid butterflies play a crucially important
      role in wing coloration as shown by spectrophotometry and scanning electron
      microscopy (SEM). The beads contain pterin pigments, which in Pieris rapae absorb
      predominantly in the ultraviolet (UV). SEM demonstrates that in the European
      subspecies Pieris rapae rapae, both males and females have dorsal wing scales
      with a high concentration of beads. In the Japanese subspecies Pieris rapae
      crucivora, however, only the males have dorsal wing scales studded with beads,
      and the dorsal scales of females lack beads. Microspectrophotometry of single
      scales without beads yields reflectance spectra that increase slightly and
      monotonically with wavelength. With beads, the reflectance is strongly reduced in
      the UV and enhanced at the longer wavelengths. By stacking several layers of
      beaded scales, pierid butterflies achieve strong colour contrasts, which are not
      realized in the dorsal wings of female P. r. crucivora. Consequently, P. r.
      crucivora exhibits a strong sexual dichroism that is absent in P. r. rapae.

PMID- 17018428
TI  - Consequences of prenatal androgen exposure for the reproductive performance of
      female pheasants (Phasianus colchicus).
AB  - Maternal hormones in vertebrate eggs can mediate important forms of maternal
      effects. However, the function of hormone transfer to the eggs is still debated,
      especially because long-term fitness consequences have been little studied. We
      investigated the effect of prenatal exposure to physiologically elevated yolk
      testosterone (T) levels on reproduction of female pheasants (Phasianus colchicus)
      in captivity. We found that females hatching from T-injected eggs (T-females) had
      a lower egg-laying rate than controls, and their eggs were more frequently
      infertile than those laid by control females. There were no effects of prenatal
      maternal treatment on egg size and yolk T concentration, but eggs carrying a
      female embryo laid by T-females had smaller yolks than eggs with a male embryo,
      while there was no sex difference in yolk size among the eggs laid by control
      females. Progeny sex ratio was unaffected by maternal treatment. These findings
      suggest that the transfer of high androgen levels to the eggs by the mother is
      constrained by complex trade-offs between direct effects on her daughters'
      reproduction and by trans-generational differential consequences on male and
      female descendants.

PMID- 17018430
TI  - Macroevolutionary dynamics in environmental space and the latitudinal diversity
      gradient in New World birds.
AB  - Correlations between species richness and climate suggest non-random occupation
      of environmental space and niche evolution through time. However, the
      evolutionary mechanisms involved remain unresolved. Here, we partition the
      occupation of environmental space into intra- and inter-clade components to
      differentiate a model based on pure conservation of ancestral niches with higher
      diversification rates in the tropics, and an adaptive radiation model based on
      shifts in adaptive peaks at the family level allowing occupation of temperate
      regions. We examined these mechanisms using within- and among-family skewness
      components based on centroids of 3560 New World bird species across four
      environmental variables. We found that the accumulation of species in the tropics
      is a result of both processes. The components of adaptive radiation have family
      level skewness of species' distributions strongly structured in space, but not
      phylogenetically, according to the integrated analyses of spatial filters and
      phylogenetic eigenvectors. Moreover, stronger radiation components were found for
      energy variables, which are often used to argue for direct climatic effects on
      diversity. Thus, the correspondence between diversity and climate may be due to
      the conservation of ancestral tropical niches coupled with repeated broad shifts
      in adaptive peaks during birds' evolutionary history more than by higher
      diversification rates driven by more energy in the tropics.

PMID- 17018429
TI  - Disease control and its selection for damaging plant virus strains in
      vegetatively propagated staple food crops; a theoretical assessment.
AB  - Viral diseases are a key constraint in the production of staple food crops in
      lesser developed countries. New and improved disease control methods are
      developed and implemented without consideration of the selective pressure they
      impose on the virus. In this paper, we analyse the evolution of within-plant
      virus titre as a response to the implementation of a range of disease control
      methods. We show that the development of new and improved disease control methods
      for viral diseases of vegetatively propagated staple food crops ought to take the
      evolutionary responses of the virus into consideration. Not doing so leads to a
      risk of failure, which can result in considerable economic losses and increased
      poverty. Specifically in vitro propagation, diagnostics and breeding methods
      carry a risk of failure due to the selection for virus strains that build up a
      high within-plant virus titre. For vegetatively propagated crops, sanitation by
      roguing has a low risk of failure owing to its combination of selecting for low
      virus titre strains as well as increasing healthy crop density.

PMID- 17018431
TI  - Metapopulation extinction risk is increased by environmental stochasticity and
      assemblage complexity.
AB  - Extinction risk is a key area of investigation for contemporary ecologists and
      conservation biologists. Practical conservation efforts for vulnerable species
      can be considerably enhanced by thoroughly understanding the ecological processes
      that interact to determine species persistence or extinction. Theory has
      highlighted the importance of both extrinsic environmental factors and intrinsic
      demographic processes. In laboratory microcosms, single-species single-habitat
      patch experimental designs have been widely used to validate the theoretical
      prediction that environmental heterogeneity can increase extinction risk. Here,
      we develop on this theme by testing the effects of fluctuating resource levels in
      experimental multispecies metapopulations. We compare a three-species host
      parasitoid assemblage that exhibits apparent competition to the individual
      pairwise, host-parasitoid interactions. Existing theory is broadly supported for
      two-species assemblages: environmental stochasticity reduces trophic interaction
      persistence time, while metapopulation structure increases persistence time.
      However, with increasing assemblage complexity, the effects of trophic
      interactions mask environmental impacts and persistence time is further reduced,
      regardless of resource renewal regime. We relate our findings to recent theory,
      highlighting the importance of taking into account both intrinsic and extrinsic
      factors, over a range of spatial scales, in order to understand resource-consumer
      dynamics.

PMID- 17018432
TI  - Recurrent replacement of mtDNA and cryptic hybridization between two sibling bat
      species Myotis myotis and Myotis blythii.
AB  - The two sibling bat species Myotis myotis and Myotis blythii occur in sympatry
      over wide areas of Southern and Central Europe. Morphological, ecological and
      previous genetic evidence supported the view that the two species constitute two
      well-differentiated groups, but recent phylogenetic analyses have shown that the
      two species share some mtDNA haplotypes when they occur in sympatry. In order to
      see whether some genetic exchange has occurred between the two species, we
      sequenced a highly variable segment of the mitochondrial control region in both
      species living in sympatry and in allopatry. We also analysed the nuclear
      diversity of 160 individuals of both species found in two mixed nursery colonies
      located north and south of the Alps. MtDNA analysis confirmed that European M.
      blythii share multiple, identical or very similar haplotypes with M. myotis.
      Since allopatric Asian M. blythii presents mtDNA sequences that are very
      divergent from those of the two species found in Europe, we postulate that the
      mitochondrial genome of the European M. blythii has been replaced by that of M.
      myotis. The analysis of nuclear diversity shows a strikingly different pattern,
      as both species are well differentiated within mixed nursery colonies (F(ST) =
      0.18). However, a Bayesian analysis of admixture reveals that the hybrids can be
      frequently observed, as about 25% of sampled M. blythii show introgressed genes
      of M. myotis origin. In contrast, less than 4% of the M. myotis analysed were
      classified as non-parental genotypes, revealing an asymmetry in the pattern of
      hybridization between the two species. These results show that the two species
      can interbreed and that the hybridization is still ongoing in the areas of
      sympatry. The persistence of well-differentiated nuclear gene pools, in spite of
      an apparent replacement of mitochondrial genome in European M. blythii by that of
      M. myotis, is best explained by a series of introgression events having occurred
      repeatedly during the recent colonization of Europe by M. blythii from Asia. The
      sharp contrast obtained from the analysis of mitochondrial and nuclear markers
      further points to the need to cautiously interpret results based on a single
      class of genetic markers.

PMID- 17018433
TI  - Evolutionary games and population dynamics: maintenance of cooperation in public
      goods games.

PMID- 17018434
TI  - The calcium-sensing receptor (CaR) and its disorders.
AB  - The system that regulates extracellular calcium (Ca(2+o)) homeostasis maintains a
      nearly constant level of Ca(2+o) so as to ensure the availability of calcium for
      its numerous intra- and extracellular roles. The molecular cloning and
      characterization of a G protein-coupled, Ca(2+o)-sensing receptor has elucidated
      the mechanism through which parathyroid cells and other cell types involved in
      calcium homeostasis sense Ca(2+o) and initiate the homeostatic responses that
      maintain Ca(2+o) at its normal level. The identification of the CaR has also
      proven unequivocally that extracellular calcium ions serve in an informational
      capacity. Furthermore, the identification of inherited human disorders resulting
      from inactivating and activating mutations of the CaR that produce hyper- and
      hypocalcemia, respectively, has provided physiological proof of the essential
      role of the CaR in mineral ion metabolism. Finally, selective activators of the
      CaR, so-called calcimimetics, are in clinical trials for the treatment of primary
      and uremic hyperparathyroidism and will likely provide the first truly effective
      medical treatment of hyperparathyroidism. CaR antagonists (calcilytics) may also
      prove to be of clinical utility in settings where inhibition of the receptor
      would be desirable.

PMID- 17018435
TI  - Sodium iodide symporter (NIS) and thyroid.

PMID- 17018436
TI  - Lack of association between Hashimoto thyroiditis and breast cancer: a
      quantitative research synthesis.
AB  - Several authors have suggested a positive association between Hashimoto
      thyroiditis (HT) and breast cancer (BrCa). Others have refuted these findings;
      hence, this subject remains controversial. We therefore reviewed the world
      literature on this subject accumulated over the last 50 years and performed a
      quantitative research synthesis, a meta-analysis variant. The incidence risk
      ratios and 95% confidence intervals (CI's) were calculated for each study and the
      combined relative risk (RR) was estimated. We found 37 relevant studies, of which
      only 13 were accessible to analysis. A significant association (RR=1.40; CI=1.29
      1.53, P<0.022) was found for 6 of the 13 studies pertaining to 1,431 women.
      However, in the cumulative population of 14,226 women (from all 13 studies), we
      failed to demonstrate an association between the diagnoses of HT and BrCa
      (RR=1.07; CI=0.99-1.15; P=0.08). In conclusion, we believe that selection bias or
      institutional referral bias, in at least some of the "positive" studies, may have
      led to the spurious recognition of an association between HT and BrCa, especially
      as both of these conditions are highly prevalent in women between the 4th and 7th
      decade of life.

PMID- 17018437
TI  - A somatic mutation in the thyrotropin receptor gene in a patient with an
      autonomous nodule within a multinodular goiter.
AB  - Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and
      acts through the thyrotropin receptor (TSHR) located on the surface membrane of
      thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the
      absence of TSH have been found in toxic adenomas and in hot nodules of
      multinodular goiters. Clinically and histologically heterogeneous nodules can
      share common gain-of-function mutations. Mutation prevalence varies greatly and
      is inversely related to iodine intake of the population. We report a Greek
      patient presenting with subclinical hyperthyroidism due to a fast-growing
      autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA
      sequencing showed that the hot nodule harbored a somatic heterozygous activating
      TSHR mutation: substitution of glutamine for leucine in the third transmembrane
      helix. This mutation (L512Q) was recently described in two solitary toxic
      adenomas. This report expands the spectrum of mutations shared by dissimilar hot
      nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The
      identification of the L512Q substitution demonstrates that gain-of-function TSHR
      mutations are encountered in Greece, although iodine deficiency has been
      significantly corrected over the last three decades.

PMID- 17018438
TI  - Pseudohypoparathyroidism type Ia and growth hormone deficiency. Growth hormone
      releasing hormone receptor defect?
AB  - We report a boy with pseudohypoparathyroidism (PHP), hypothyroidism and low
      growth hormone (GH) values with no response to growth hormone releasing hormone
      (GHRH). He presented at age 17 mo because of developmental delay. He had the
      typical features (short stature, obesity, round face, brachydactyly) of
      Albright's hereditary osteodystrophy (AHO) and the biochemical profile of PHP;
      low serum calcium and high phosphate, raised parathormone (PTH) values and lack
      of response of urinary phosphate and cyclic AMP to PTH administration. The serum
      total thyroxine value (T4) was 37.32 nmol/L and the thyroid stimulating hormone
      (TSH) 29 mU/L. Peak GH values during two provocative tests (Glucagon, L-Dopa)
      were <2.5 microg/L and <1.7 microg/L, respectively, while following GHRH
      administration the maximum GH value was 0.2 microg/L. The IGFI value was 65 ng/ml
      and rose to 253 ng/ml after GH administration for three days. This boy had PTH
      and TSH receptor defect and we speculate that he also has GHRH receptor defect.

PMID- 17018440
TI  - Endocrine terminology in Corpus Hippocraticum.

PMID- 17018439
TI  - Contribution of high-resolution ultrasonography in the differential diagnosis of
      benign from malignant thyroid nodules.
AB  - The purpose of this study was to investigate the value of "high-resolution
      ultrasonography" in the differential diagnosis of benign from malignant thyroid
      nodules. The study included ultrasonography examination of 77 patients with
      thyroid nodules, who underwent thyroidectomy. The histological findings were
      subsequently compared with pre-operative sonographic findings. Thirty patients
      had malignant nodules and 47 patients had benign nodules. The sonographic
      features that were studied were: hypoechogenicity or isoechogenicity of the
      nodules, the presence of peripheral halo, the regular or irregular contour, the
      presence of microcalcifications, the presence of cystic degeneration and the
      existence of solitary or multiple nodules. The results revealed that low
      echogenicity constitutes a sonographic feature of malignancy with high
      sensitivity and medium specificity. The presence of microcalcifications is a
      feature of malignancy with low sensitivity but high specificity. Conversely, the
      regular contour of a nodule and the presence of peripheral halo are features of
      benign nodule with high sensitivity and specificity. Cystic degeneration occurs
      at the same rate in benign and malignant nodules. Solitary nodules were malignant
      more often than were multiple nodules, a finding that was not, however,
      statistically significant. We conclude that high-resolution ultrasonography
      contributes greatly in the preoperative differential diagnosis of thyroid
      nodules. It constitutes an important diagnostic means complementary to needle
      biopsy in the management of thyroid nodules and it is even more valuable in those
      nodules that cannot undergo biopsy.

PMID- 17018441
TI  - Stress neuropeptides in the human endometrium: paracrine effects on cell
      differentiation and apoptosis.
AB  - Human endometrium exhibits characteristics of a neuroendocrine-like stress organ
      in addition to its classical role as the main target of ovarian steroid hormones.
      Indeed, the epithelial cells of human endometrium express the stress-associated
      neuropeptide genes corticotropin-releasing hormone (CRH), proopiomelanocortin,
      proenkephalin and prodynorphin. Furthermore, endometrium stroma cells also
      express CRH when they differentiate into decidual cells. Multiple lines of
      evidence suggest that the stress-associated neuropeptides of human endometrium
      are under the endocrine control of gonadal steroids as well as under an
      autocrine/paracrine regulation by prostanoids and interleukins. Endometrial
      stress-associated neuropeptides appear to exert their biological effect locally,
      i.e. within the uterus since human endometrium and myometrium also express the
      relevant receptors. More specifically, recent data suggest that endometrial CRH
      participates in the regulation of intrauterine inflammatory processes taking
      place in early pregnancy including stroma decidualization, blastocyst
      implantation and early maternal tolerance. Similarly, endometrial opioids
      participate in the regulation of uterine tissue remodeling via their effect on
      endometrial cell apoptosis. Thus, endometrial stress neuropeptides act as
      paracrine regulators of uterine cell differentiation and tissue remodeling as
      well as modulators of local immune responses.

PMID- 17018443
TI  - Endemic goiter--an update.

PMID- 17018442
TI  - Treatment of advanced neuroendocrine tumours with the radiolabelled somatostatin
      analogue octreotide.
AB  - Neuroendocrine tumours (NET) have a particular tendency to express functional
      receptors and/or uptake mechanisms. Radionuclides, such as (111)In-pentetreotide,
      a somatostatin analogue, which bind to somatostatin receptors, present an imaging
      modality that has been used for both the diagnosis and staging of NET.
      Scintigraphy with (111)In-pentetreotide can identify lesions beyond the
      diagnostic sensitivity of conventional imaging modalities. In addition, NET that
      demonstrate positive uptake to a diagnostic (111)In-pentetreotide can, in theory,
      be treated with these radionuclides, thus presenting a novel and evolving
      therapeutic modality in addition to other traditional therapeutic approaches.
      Although experience with (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide therapy is still
      limited, preliminary studies have demonstrated useful activity in a variety of
      NET with limited side-effects. Large phase II clinical trials using (90)Y-DOTA-D
      Phe(1)-Tyr(3)-octreotide therapy are still on-going and the results are expected
      to be presented soon. In order to improve the response rates obtained, newer
      somatostatin analogues are being developed and the combination with other beta
      emitting particles in addition to (90)Y is being considered.

PMID- 17018444
TI  - Compensatory adrenal growth in relation to stress of surgery and estradiol in
      adult male rats.
AB  - ACTH infusion at the time of unilateral adrenalectomy inhibits the early rapid
      compensatory growth (CAG) in the remaining adrenal. We examined the hypothesis
      that different duration of surgery and/or the enhanced response to the stress of
      surgery, induced by estradiol treatment, might modify CAG. Adult male rats
      untreated, estradiol benzoate treated (EB) 300 microg/kg or vehicle treated (VE)
      for 3 days, were Sham or left adrenalectomized after 18 to 20 min procedure
      (prolonged surgery) or after 14 to 16 min procedure (short surgery). The response
      to surgical stress was evaluated by comparison of the left adrenals between Sham
      and left adrenalectomized animals matched for treatment, surgery and body weight.
      Autopsy was done 88-90 h after surgery. The right adrenals following prolonged
      surgery for unilateral adrenalectomy after EB or VE treatment were examined
      histologically. The number of rats with enlarged zona glomerulosa was greater
      (p<0.01) in EB than in VE-treated rats. Prolonged surgery induced significant
      stress response in untreated and EB-treated rats in parallel with attenuation of
      CAG. Stress response of lower magnitude in VE (22%) than in EB-treated rats
      (61.4%) was followed by significant CAG. After short duration surgery,
      significant CAG, with an absence of stress response, was apparent in VE and EB
      rats. The extent of CAG was found inversely related to initial adrenal size. In
      conclusion, these results suggest that prolonged surgical stress, increased
      response to this stress and enlarged glomerulosa are negatively related to CAG,
      possibly through CAG suppression by increased ACTH and/or adrenocortical
      secretion.

PMID- 17018445
TI  - Differentiated thyroid cancer in Greece: 1963-2000. Relation to demographic and
      environmental factors.
AB  - Thyroid cancer (TC) is a relatively rare neoplasia, accounting for 0.35%-0.38% of
      total deaths due to cancer in Greece. Environmental/nutritional factors are
      considered to play a role in its pathogenesis. The aim of this retrospective
      review of patients' histories from three of the largest specialized centers in
      southern Greece, from 1963 to 2000, was to assess associations of differentiated
      TC (DTC) with demographic and environmental factors. The total number of DTC
      cases was 610 (119 men or 19.5%, and 491 women or 80.5%), of which 442 cases
      (72%) were papillary DTCs (pure papillary type: 54.5% and mixed papillary
      follicular type: 45.5%), 90 cases (15%) were of the pure follicular type, while
      78 cases (13%) were classified as suspicious lesions, requiring follow-up, but
      not definitively carcinomas. The mean age (+/-SD) at diagnosis for all groups was
      42.3+/-1.3 years. Fifty percent of the patients were living in Athens at the time
      of diagnosis. The diagnosis was delayed in patients living in villages compared
      to those living in cities (mean age +/-SD): 43.7+/-14.1 years and 40.9+/-13.8
      years, respectively; p<0.05, t-test). Patients who were born in iodine-sufficient
      areas (n=162/193, 84%; X(2)=5.09, P=0.02) had papillary carcinoma more frequently
      compared to patients who were born in previously iodine-deficient areas
      (n=159/214, 74%). During the observation period (1963-2000) there appeared to be
      three different trends in the incidence of newly diagnosed cases: a random
      variation during the first nine years and a steady increase during the second two
      decades (starting before the Chernobyl nuclear accident) followed by a
      significant decline during the last few years. We suggest that the observed
      variations in the incidence of DTC could be related to the availability of
      diagnostic tools as well as to increased awareness.

PMID- 17018446
TI  - beta-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek
      population.
AB  - beta-thalassemia (beta-thal) is characterized by disturbances of the reproductive
      system. The aim of the present study was: 1) to assess the hypothalamic-
      pituitary-gonadal axis in patients with beta-thal in relation to their phenotype
      and 2) to determine prognostic features of current gonadal status. We studied 135
      patients (67 males and 68 females) with beta-thal through history, physical
      examination, spermiograms and GnRH test. These patients were divided into beta
      thal major (51 males and 62 females) and beta-thal intermedia phenotypes (16
      males and 6 females). Male patients with beta-thal major were subdivided into
      three groups a) eugonadal (35%, Tanner's stage V, normal testicular volume,
      normal spermiograms, normal basal and stimulated hormone values), b) patients
      with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanner's stage II-V,
      low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin
      values and abnormal response to GnRH test) and c) patients with HH of early onset
      (41%, Tanner's stage I, small testicular volume, abnormal spermiograms, abnormal
      basal and stimulated hormone values). Female patients with beta-thal major were
      subdivided into: a) eugonadal (32%, Tanner's stage V, regular menstruation,
      normal basal and stimulated hormone values), b) patients with hypogonadotrophic
      hypogonadism (HH) of late onset (34%, Tanner's stage II-V, secondary amenorrhea,
      subnormal basal and stimulated gonadotrophin values) and c) patients with HH of
      early onset (34%, Tanner's stage I, primary amenorrhea, subnormal basal and
      stimulated hormone values). Patients with beta-thal intermedia were subdivided
      into eugonadal (75% of males, 33% of females) and hypogonadal (25% of males, 67%
      of females). Current gonadal status could not be predicted by means of
      transfusion or chelation parameters. In conclusion, beta-thal patients could be
      eugonadal or develop early or late onset HH. trade mark-thal intermedia patients
      have a more favorable profile than beta-thal major individuals. Current gonadal
      status of beta-thal patients cannot be predicted by means of history, clinical or
      laboratory parameters.

PMID- 17018447
TI  - Pitutaty insufficiency. Diagnosis masked by a toxic thyroid adenoma.
AB  - A patient with undiagnosed pituitary insufficiency who also had a toxic thyroid
      adenoma is presented. The T3 secreted by the adenoma apparently corrected the
      secondary thyroid failure, but also aggravated the secondary adrenal failure and
      almost precipitated adrenal crisis. The diagnostic work-up in such an unusual co
      existence is discussed, in particular since the clinical diagnosis of pituitary
      insufficiency in the elderly is not easily established.

PMID- 17018448
TI  - Fuller Albright 1900-1969.

PMID- 17018449
TI  - Leptin, nutrition and reproduction: new insights.
AB  - Recent data suggest that in addition to leptin's role in conveying signals of the
      amount of energy stores to the central nervous system, this adipocyte secreted
      hormone interacts with the endocrine system to provide critical information about
      the size of fat stores, acting as a permissive factor that allows the triggering
      of energy demanding situations as the onset of puberty and reproduction. Animal
      and human data are concordant with the concept that leptin plays an important
      permissive role in the initiation of puberty and in maintenance of reproductive
      function thereafter. Leptin regulates the gonadotropin-gonadal axis at a central
      level. The hypothalamus is an important site of leptin's action where a complex
      network of neuropeptides is involved in leptin's effect on GnRH. In addition,
      leptin plays a role during pregnancy and lactation as it is produced by the
      placenta and is present in milk. Plasma leptin levels are elevated during
      pregnancy and this hyperleptinemia is not accompanied by a reduction in food
      intake, suggesting a state of leptin resistance. Leptin is also detected in the
      amniotic fluid and its levels are high in venous cord blood at delivery
      correlating positively with weight at birth which suggests a potential role in
      intrauterine growth. The fact that in females leptin levels are higher than in
      males, even when corrected for body fat, suggests that the reproductive system is
      modulated by leptin in a different way in males and females estrogens. In
      hypoleptinemia resulting from specific genetic causes, leptin levels may still be
      adequate for the function of the reproductive system in humans, a phenomenon
      which differs from the findings in leptin-deficient animals which are infertile.
      Due to species differences in the role of leptin, it is difficult to extrapolate
      data from rodents to human physiology. However hypoleptinemia due to non-genetic
      causes such as anorexia nervosa and exercise leads to loss of reproductive
      function. Genetic/developmental factors influence the threshold required to turn
      off the behavioral, metabolic and endocrine responses to perceived caloric
      deprivation.

PMID- 17018450
TI  - Dyslipidemia in patients with thyroid disorders.
AB  - Thyroid disorders are known to influence lipid metabolism and are common in
      dyslipidemic patients. Overt and subclinical hypothyroidism have an adverse
      effect on the serum lipid profile that may predispose to the development of
      atherosclerotic disease. Although thyroid substitution therapy is beneficial for
      patients with overt hypothyroidism, the question of whether subclinical
      hypothyroidism must be treated remains unanswered. The association between
      thyroid autoimmunity and lipoprotein (a) levels is controversial. Hyperthyroidism
      may be the underlying cause for acquired hypocholesterolemia or unexpected
      improvement of the lipid profile of a previously hyperlipidemic patient.

PMID- 17018451
TI  - Structure-function relationships of glycoprotein hormones; lessons from mutations
      and polymorphisms of the thyrotrophin and gonadotrophin subunit genes.
AB  - The pituitary glycoprotein hormones thyrotrophin (thyroid-stimulating hormone,
      TSH), lutrophin (luteinising hormone, LH) and follitrophin (follicle-stimulating
      hormone, FSH), as well as the placental choriongonadotrophin (human chorionic
      gonadotrophin, hCG) are composed of a common alpha-subunit and a specific beta
      subunit, coupled by noncovalent interactions. Formation of alpha/beta dimers is
      necessary for their biological function. Mutations and polymorphisms in the genes
      encoding these hormones are relatively rare, apparently because of their vital
      role in the regulation of reproductive and metabolic functions. However, a few
      genetic alterations in these genes have been identified and offer valuable, novel
      information about the structure-function relationships of the glycoprotein
      hormones. The purpose of this review is to present the known mutations and
      polymorphisms of the TSH, LH and FSH subunit genes and describe their functional
      consequences as causative factors of hypothyroidism and hypogonadism. Because
      genuinely inactivating TSH and gonadotrophin mutations are extremely rare, they
      are unlikely to be encountered in clinical practice. However, some of the
      polymorphisms are relatively common and because they may change the
      immunoreactivity of the hormone, they may result in aberrant laboratory findings.

PMID- 17018452
TI  - Glucocortidoid sensitivity assessed in peripheral blood cells do not correlate
      with the feedback sensitivity of the hypothalamo-pituitary adrenal AXIS.
AB  - Glucocorticoids (GC) affect virtually all organ systems, acting mainly via the
      glucocorticoid receptor (GR). The immune system is the best characterized tissue
      for assessing GC sensitivity. It is well established that the immune system GC
      sensitivity varies widely between normal subjects. However, it remains unclear
      whether measurements of the immune system GC-sensitivity reflect the GC
      sensitivity in other GC target tissues of the same individual. Thus, in the
      present study we compared the GC sensitivity of the immune system, assessed by
      determining the dexamethasone inhibition of LPS-induced TNF-alpha production in
      peripheral leukocytes, with the feedback sensitivity of the HPA axis, assessed by
      a very low dose dexamethasone (0.25 mg) suppression test, in sixteen healthy
      volunteers. We observed a wide variation in the magnitude of the responses in the
      two GC targets. However, and in agreement with a number of previous reports, in a
      given subject the GC sensitivity of the immune system did not correlate with that
      of HPA axis inhibition, indicating a tissue specificity of GC sensitivity in the
      same individual. In summary, the bulk of current evidence suggests that GC
      sensitivity is tissue specific for a given individual. Additional studies are
      warranted to elucidate the exact mechanism(s) involved in the differential GC
      tissue responsiveness.

PMID- 17018453
TI  - Continuous combined replacement therapy in postmenopausal women: effect on plasma
      lipoproteins, bone mass and the endometrium.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of Hormone
      Replacement Therapy (HRT) on plasma lipoprotein levels, bone mass and the
      endometrium. METHODS: Thirty healthy women were enrolled in the study for
      climacteric symptoms and received a combination of 17beta-estradiol and
      norethisterone acetate continuously for 2 years. An untreated group, consisting
      of 25 healthy postmenopausal women presenting the same symptoms and not willing
      to receive HRT, were also studied and served as controls. Plasma lipoprotein
      levels, bone mineral density as well as thickness of the endometrium measured by
      ultrasound and biopsy of the endometrium were evaluated at baseline and after 1
      and 2 years. There were no differences between the two groups regarding clinical
      and demographic baseline data. RESULTS: After 2 years of HRT, total cholesterol
      and LDL-cholesterol levels were significantly reduced (p<0.05). Changes in serum
      triglyceride and HDL-cholesterol levels were not statistically significant.
      Levels of lipoprotein (a) showed a statistically significant decrease at 1(st)
      and 2(nd) year (p<0.05) in both groups while levels of ApoA1 and ApoB were
      significantly lower only in the HRT group compared to the baseline values. After
      2 years of HRT, biomarkers of bone metabolism showed a significant decline, while
      endometrium was atrophic in 93.3% of the cases. CONCLUSIONS: Hormone replacement
      therapy (17beta-estradiol combined with norethisterone acetate) was associated
      with favorable changes in the lipid status and bone metabolism. Endometrium was
      atrophic in most of the treated subjects.

PMID- 17018454
TI  - Secular growth changes in the Hellenic population in the twentieth century.
AB  - Statural growth is dependent on hereditary and environmental factors, i.e
      disease, nutrition. The improvement of socioeconomic conditions that took place
      during the 20th century resulted in a secular trend towards greater height and
      earlier sexual maturation. Greek society has changed dramatically from a mainly
      agricultural society at the beginning of the 20th century to a mainly urban one
      in the second half of the century, and during this period Greece became a
      developed country. The various studies examining the height of children living in
      Athens during this period show a gradual increase in the height of children, the
      difference of the mean height between 2001 and 1928 being 11.8 cm and 7.3 cm for
      17 year old boys and girls, respectively. The difference in mean height was
      present at all ages. The difference in final height was mainly due to prepubertal
      growth. Girls at the age of 10 and boys at 11 years were about 8 cm taller in
      2001 than in 1928. A growth study carried out on conscripts in 1990 found no
      significant difference in the height of males coming from urban or rural areas of
      the country, whereas such a difference was detected in 1968, rural men being
      significantly shorter than urban ones in 1968. There are only a few studies on
      the sexual maturation of Greek children. The available data suggest a secular
      trend towards earlier puberty in females; however, this can not be substantiated
      for males. Menarcheal age in Greek girls showed a positive secular change that is
      in agreement with the observed trend for earlier pubertal maturation in girls. In
      conclusion, Greek children in the 20th century experienced a positive secular
      trend in stature which also includes final height. A secular trend for earlier
      sexual maturation can be shown only for girls.

PMID- 17018455
TI  - Testicular leydig cell tumor presenting as primary infertility.
AB  - A 29-year old male and his wife presented with an 18 month history of primary
      infertility. History and initial investigations suggested no major female
      pathologic component but a semen analysis revealed azoospermia. There was no
      history of any sexual dysfunction and neither partner was receiving any
      medication. Clinical examination revealed normal secondary sexual
      characteristics. Both testicles were of normal consistency with a volume of
      approximately 15 ml but a 4 x 2 cm mass was palpable at the lower pole of the
      left testis. Laboratory investigations revealed: serum testosterone 37.1 nmol/l
      (NV:10.0-38.0 nmol/l), LH<0.3 U/L (NV:3.0-12.0 U/L), and FSH <0.1 IU/L (NV:3.0
      11.0 U/L). Serum b-HCG, aFP, LDH, oestradiol and inhibin levels were within the
      normal range. A repeated semen analysis confirmed azoospermia. Testicular
      ultrasound demonstrated a well-defined hypoechoic mass, measuring 31 x 23 x 17 mm
      and containing several flecks of calcification, arising from the lower pole of
      the left testis. A left orchidectomy was performed. Macroscopical
      histopathological examination revealed a single firm dark brown nodule 2.8 cm in
      diameter arising from the lower pole of the testis. The tumor distended the
      capsule of the testis without extending through it. Microscopical examination was
      consistent with a Leydig cell tumor. Computerised tomography of the chest,
      abdomen and pelvis was normal. Six months later, laboratory investigations
      revealed a serum testosterone of 14.3 nmol/l, an LH of 5.4 U/L and an FSH of 4.3
      U/L, respectively. A repeated semen analysis was normal: volume 1.8 ml(2-10 ml),
      count 124 x 10(6) (20-350 x 10(6)), motility 80%(>60%), abnormal forms
      <15%(<15%). Three months later his wife was pregnant. In summary, our patient
      presented with azoospermia, secondary to a Leydig cell tumor, which was
      reversible after removal of the tumor.

PMID- 17018456
TI  - Primary malignant fibrous histiocytoma on the thyroid.
AB  - A 42-year old white female with a primary Malignant Fibrous Histiocytoma (MFH) is
      described. The patient was examined for a "cold" nodule of the thyroid diagnosed
      five years previously. The patient had been on L-thyroxine therapy for three
      years which was discontinued by the patient 18 months prior to the present visit.
      Fine needle aspiration of the thyroid nodule indicated a low differentiated
      neoplasm with some mucous production. The patient underwent total thyroidectomy
      and excision of the infiltrated part of the anterior cervical muscles. The
      histology showed MFH on the thyroid, an extremely rare primary localization of
      this neoplasm. For the subsequent 8 years, the patient was well with no evidence
      of recurrence or metastasis. Afterwards, she developed a fast growing nodal
      structure on the mitral valve, leading to its surgical replacement. This
      operation was followed by several thromboembolic episodes (pulmonary and
      cerebral) which led to her death 10 years after thyroidectomy.

PMID- 17018457
TI  - Pycnodysostosis: Toulouse-Lautrec's and Aesop's disease?

PMID- 17018458
TI  - Cardiorespiratory fitness levels among US youth 12 to 19 years of age: findings
      from the 1999-2002 National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: To assess cardiorespiratory fitness levels in youth aged 12 to 19
      years and to examine associations between fitness and age, sex, race/ethnicity,
      and self-reported physical activity in this age group. DESIGN: Cross-sectional
      study. SETTING: The National Health and Nutrition Examination Survey's mobile
      examination center, throughout the United States from 1999-2002. PARTICIPANTS: A
      representative sample of 4732 youth aged 12 to 19 years was examined; 3287
      completed the treadmill test and were included in the analysis. The National
      Center for Health Statistics conducted the survey. Main Exposures Age, sex,
      race/ethnicity, weight status, self-reported physical activity, and television
      viewing. Main Outcome Measure Estimated maximal oxygen uptake (VO2max) determined
      by a submaximal treadmill exercise test. RESULTS: Estimated VO2max (mL.kg(-1) .
      min(-1)) was higher in males (mean +/- SE, 46.4 +/- 0.4) than in females (mean +/
      SE, 38.7 +/- 0.3) but did not differ across race/ethnicity groups. Among males,
      older participants had higher VO2max values, while in females, younger
      participants had higher values. For both males and females, those in the normal
      weight group had higher fitness levels than those in the at risk for overweight
      and overweight groups. Approximately one third of both males and females failed
      to meet recommended standards for cardiorespiratory fitness. CONCLUSIONS: In US
      youth, cardiorespiratory fitness is lower in males and females who are overweight
      than in those of normal weight, but fitness is not related to race/ethnicity.
      Youth who have low levels of physical activity and high levels of sedentary
      behavior are also more likely to have lower cardiorespiratory fitness.

PMID- 17018459
TI  - Attenuating growth in children with profound developmental disability: a new
      approach to an old dilemma.
AB  - Caring for children with profound developmental disabilities can be difficult and
      demanding. For nonambulatory children with severe, combined neurologic and
      cognitive impairment, all the necessities of life must be provided by caregivers,
      usually parents, and these tasks become more difficult as the child grows to
      adolescence and adulthood. Many parents would like to continue caring for their
      child with special needs at home but find it difficult to do so as the child
      increases in size. If growth could be permanently arrested while the child was
      still small, both child and parent would likely benefit because this would
      facilitate the option of continued care in the home. Treatment of the child with
      high-dose estrogen, initiated at an early age, could provide this option. High
      dose estrogen both inhibits growth and rapidly advances maturation of the
      epiphyseal growth plates, bringing about permanent attenuation in size after a
      relatively short period of treatment. We present a case report and discuss the
      medical and ethical considerations of such an intervention strategy. We suggest
      that after proper screening and informed consent, growth-attenuation therapy
      should be a therapeutic option available to these children should their parents
      request it.

PMID- 17018460
TI  - Improved preventive care for asthma: a randomized trial of clinician prompting in
      pediatric offices.
AB  - OBJECTIVE: To determine whether clinician prompting regarding a child's symptom
      severity and guideline recommendations at the time of an office visit improves
      the delivery of preventive asthma care. DESIGN: Randomized controlled trial.
      SETTING: Two inner-city pediatric practices in Rochester, NY. PARTICIPANTS: Two
      hundred twenty-six children with persistent asthma (aged 2-12 years) presenting
      to the clinics for well-child care, asthma care, or non-asthma-related illness
      care. Intervention We assigned children randomly to a clinician-prompting group
      (single-page prompt including the child's symptoms and guideline recommendations
      given to the clinician at the time of the visit) or a standard-care group (no
      prompt given). Interviewers called parents after the visit to inquire about
      preventive measures taken, and medical charts were reviewed. MAIN OUTCOME
      MEASURES: Any preventive action related to asthma taken at the visit. RESULTS:
      Children in the clinician-prompting group were more likely to have had any
      preventive measures taken at the visit compared with children in the standard
      care group (87% vs 69%). Specifically, visits for children in the clinician
      prompting group were more likely to include delivery of an action plan (50% vs
      24%), discussions regarding asthma (87% vs 76%), and recommendations for an
      asthma follow-up visit (54% vs 37%). In a regression model, children in the
      clinician-prompting group had 3-fold greater odds of receiving any preventive
      action compared with the standard-care group. CONCLUSION: Clinician prompting
      regarding asthma severity and care guidelines at the time of an office visit
      significantly improved the delivery of preventive asthma care.

PMID- 17018462
TI  - Tall girls: the social shaping of a medical therapy.
AB  - During the latter half of the 20th century, estrogen therapy was administered to
      prevent otherwise healthy girls with tall stature from becoming tall adults by
      inhibiting further linear growth. We explore how decisions to treat tall girls
      with estrogen were influenced by both scientific knowledge and sociologic norms.
      Estrogen therapy represented the logical application of scientific knowledge
      regarding the role of estrogen for closure of the growth plates, but it also
      reflected prevailing societal and political beliefs about what it meant to be a
      tall girl. We discuss the rise and fall in popularity of this therapy and suggest
      that insight into the present-day treatment of short stature can be gained by
      comparing the use of estrogen therapy for tall girls with the use of growth
      hormone therapy for short boys. We suggest that this case study illustrates how
      scientific knowledge is always created and applied within a particular social
      context.

PMID- 17018461
TI  - Adolescent bone health.
AB  - Pediatric and adolescent care professionals have increasingly recognized the
      importance of understanding the skeletal health of their patients. Peak bone
      mass, the "bone bank" on which an individual will draw for their entire adult
      life, is likely achieved by late adolescence, with the critical window for
      accumulation occurring much earlier. This review outlines the known conditions
      that are associated with impaired bone mineral accrual and clinical settings in
      which the evaluation of "at-risk" adolescents should be considered. We describe
      the methods available to the health care professional for evaluating bone
      density, along with the limitations of each technology. Potential therapeutic
      options for patients identified to have a low bone mineral density are discussed.
      Finally, current recommendations regarding physical activity and nutrition,
      beneficial interventions for all adolescents, are presented.

PMID- 17018463
TI  - Motor and cognitive outcomes in nondisabled low-birth-weight adolescents: early
      determinants.
AB  - OBJECTIVES: To describe motor and cognitive outcomes in nondisabled low-birth
      weight (LBW) adolescents and to determine the relation of specific prenatal,
      perinatal, and neonatal risk factors to these outcomes. DESIGN: A prospective
      epidemiological study. SETTING: An adolescent follow-up of a regional LBW (<2000
      g) cohort born in or admitted to 3 hospitals between September 1, 1984, and June
      30, 1987 (n = 1105). Of 862 eligible survivors, 628 (72.9%) underwent assessment
      at a mean age of 16 years; of these, 33 had severe disability that precluded
      psychometric evaluation. The 474 nondisabled adolescents undergoing assessment at
      home had slightly less social risk at birth than did all other nondisabled
      eligible adolescents. PARTICIPANTS: The 474 nondisabled LBW adolescents assessed
      at home. Main Exposures Basic birth characteristics (social risk, sex, fetal
      growth ratio, and gestational age), neonatal cranial ultrasound abnormalities,
      and other early medical complications. MAIN OUTCOME MEASURES: Riley Motor
      Problems Inventory and Wechsler Abbreviated Scales of Intelligence. RESULTS:
      Nondisabled LBW adolescents had an excess of motor problems compared with the
      normative sample. The IQ scores, although within the normal range, were
      significantly lower than population norms. Independent predictors of total motor
      problems included male sex, white matter injury on neonatal ultrasound, and days
      of ventilation. Independent predictors of lower Full Scale IQ scores included
      social disadvantage, fetal growth ratio, and white matter injury on neonatal
      ultrasound. CONCLUSIONS: Specific prenatal, perinatal, and neonatal risk factors
      influence motor and cognitive performance in nondisabled LBW survivors well into
      adolescence, even when controlling for social risk. Advances in maternal-fetal
      and neonatal care can substantially improve these long-term outcomes.

PMID- 17018464
TI  - Ethanol-lock technique for persistent bacteremia of long-term intravascular
      devices in pediatric patients.
AB  - OBJECTIVES: To use the ethanol-lock technique (in conjunction with systemic
      antibiotics) to salvage central lines from removal and to prevent persistence of
      catheter-related infections among pediatric patients with long-term intravascular
      devices. DESIGN: Medical records of patients treated with ethanol locks were
      retrospectively reviewed from June 1, 2004, through June 22, 2005. SETTING:
      Childrens Hospital Los Angeles, Los Angeles, Calif, a tertiary care pediatric
      hospital. Patients Forty children with diverse underlying disorders were treated
      for 51 catheter-related infections using the Childrens Hospital Los Angeles
      ethanol-lock technique. INTERVENTIONS: Eligible infected central lines were
      instilled with a dose volume of 0.8 to 1.4 mL of 70% ethanol into the catheter
      lumen during 12 to 24 hours and then withdrawn. The volume of ethanol used was
      based on the type of intravascular device. MAIN OUTCOME MEASURES: Clearance of
      infection and incidence of recurrence. RESULTS: Of the 51 ethanol-lock treatments
      in 40 children, no catheters were removed because of persistent infection. Eighty
      eight percent (45/51) of the treated episodes cleared without recurrence (defined
      as a relapse within 30 days with the same pathogen). Twelve (75%) of 16
      polymicrobial isolates and 33 (94%) of 35 monomicrobial isolates were
      successfully treated. There were no adverse reactions or adverse effects
      reported. CONCLUSION: This retrospective study supports the use of the ethanol
      lock technique in conjunction with systemic antibiotics as an effective and safe
      method to retain the use of a previously infected central venous catheter,
      decrease the need for line removal, and eradicate persistent pathogens in
      catheter-related infections.

PMID- 17018465
TI  - Inpatient health care use among adult survivors of chronic childhood illnesses in
      the United States.
AB  - OBJECTIVES: To describe the inpatient length of stay and related charges for
      adults in the United States with childhood-onset chronic disease and to examine
      patterns with respect to different hospital settings. DESIGN: We analyzed data
      from the 2002 Nationwide Inpatient Sample, a nationally representative data set
      of hospital discharges. We performed a case-mix-adjusted, sample-weighted
      regression analysis as well as descriptive statistics of hospital use among
      adults with childhood-onset chronic disease. SETTING: United States.
      PARTICIPANTS: We identified hospitalizations for persons aged 18 years or older
      with a diagnosis of complex congenital heart disease, cystic fibrosis, sickle
      cell disease, or spina bifida. Main Exposure Childhood chronic illness. MAIN
      OUTCOME MEASURES: Length of stay and total charges among pediatric, adult, and
      mixed hospitals. RESULTS: In multivariate adjusted analyses, patients with
      complex congenital heart disease and cystic fibrosis had a significantly longer
      length of stay in pediatric hospitals than in adult or mixed hospitals (P<.001);
      no similar difference was found for sickle cell disease and spina bifida. For all
      of the 4 conditions, hospital charges were significantly greater in pediatric
      hospitals than in adult or mixed hospitals (P<.001 for cystic fibrosis, complex
      congenital heart disease, and sickle cell disease, and P<.01 for spina bifida).
      CONCLUSIONS: The vast majority of persons who have survived to adulthood with
      complex congenital heart disease, cystic fibrosis, spina bifida, or sickle cell
      disease are hospitalized in hospitals that predominantly care for adults, where
      charges for care appear to be lower than in pediatric hospitals.

PMID- 17018466
TI  - Attention-deficit/hyperactivity disorder in children: excess costs before and
      after initial diagnosis and treatment cost differences by ethnicity.
AB  - OBJECTIVES: To estimate the excess costs for children in the years surrounding
      initial diagnosis of attention-deficit/hyperactivity disorder (ADHD) and to
      estimate differences in treatment costs by ethnicity. DESIGN: We identified
      children diagnosed with ADHD and estimated their health service costs in the 2
      years before and 2 years after initial diagnosis of ADHD. Costs were compared
      with those for children without ADHD. We adjusted for age, sex, ethnicity,
      pharmacy co-pay, estimated family income, coexisting mental health disorders, and
      chronic medical conditions. SETTING: Nonprofit, integrated health care delivery
      system in northern California from January 1, 1996, to December 31, 2004.
      PARTICIPANTS: Children aged 2 to 10 years with (n = 3122) and without (n = 15
      899) ADHD. Main Exposure Attention-deficit/hyperactivity disorder. MAIN OUTCOME
      MEASURES: Health care costs and use in the years before and after initial ADHD
      diagnosis as well as costs of ADHD-related services. RESULTS: Compared with
      children without ADHD, children with ADHD had mean costs that were $488 more in
      the second year before their ADHD diagnosis, $678 more in the year before their
      diagnosis, $1328 more in the year after their diagnosis, and $1040 more in the
      second year after their diagnosis. Asian Americans diagnosed with ADHD had lower
      total ADHD-related mean costs per year than white Americans diagnosed with ADHD
      ($221 lower), and Asian Americans, African Americans, and Hispanic Americans all
      had lower ADHD-related pharmacy mean costs than white Americans ($95, $63, and
      $77 lower, respectively). CONCLUSIONS: Children with ADHD use significantly more
      health services before and after their diagnosis than children without ADHD.
      Among children diagnosed with ADHD, nonwhite Americans (especially Asian
      Americans) use fewer ADHD-related services than white Americans.

PMID- 17018468
TI  - Growth attenuation: a diminutive solution to a daunting problem.

PMID- 17018467
TI  - Cost-effectiveness analysis of palivizumab in premature infants without chronic
      lung disease.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of palivizumab as respiratory
      syncytial virus prophylaxis in premature infants without chronic lung disease and
      to evaluate the impact on cost-effectiveness of a potential reduction in risk of
      asthma following respiratory syncytial virus infection among infants receiving
      palivizumab. DESIGN: Two decision analytic models were designed, one with and the
      other without accounting for increased risk of asthma following respiratory
      syncytial virus infection. SETTING: A hypothetical community or university
      hospital. PARTICIPANTS: Hypothetical cohorts of infants without chronic lung
      disease born at 26 to 32 weeks' gestation. INTERVENTIONS: Palivizumab prophylaxis
      vs no prophylaxis. MAIN OUTCOME MEASURES: Expected costs and incremental cost
      effectiveness ratio expressed as cost per quality-adjusted life-year. RESULTS:
      The expected costs were higher for palivizumab prophylaxis as compared with no
      prophylaxis. The incremental cost-effectiveness ratios were high for all
      gestations and are not considered cost-effective by today's standards (<$200 000
      per quality-adjusted life-year). Both models were sensitive to variation in the
      cost of palivizumab. The model that included asthma was sensitive to variation in
      quality of life for children with asthma. In instances where asthma was
      considered severe with profound worsening in quality of life compared with life
      without asthma, some infants had an incremental cost per quality-adjusted life
      year that was less than $200 000. CONCLUSIONS: Our model supports implementing
      more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost
      effective for some infants in an analysis that accounted for increased risk of
      severe asthma following respiratory syncytial virus infection.

PMID- 17018469
TI  - At what cost?

PMID- 17018470
TI  - Picture of the month. Neurocysticercosis.

PMID- 17018471
TI  - New technology in gynecologic surgery: is new necessarily better?

PMID- 17018472
TI  - Uterine rupture in primigravid women.

PMID- 17018473
TI  - Lessons from a case report.

PMID- 17018474
TI  - Bilateral bladder erosion of a transobturator tape mesh.
AB  - BACKGROUND: The transobturator tape procedure is reported to be an effective
      procedure with low complication rates. CASE: A 45-year-old woman underwent
      surgery for prolapse and incontinence. The surgery included transobturator tape.
      Intraoperative cystoscopy was not performed. Postoperatively, a mesh erosion into
      the bladder on the left side and a large cystocele were diagnosed. The patient
      underwent a combined transurethral and suprapubic mesh resection. Six months
      later, she had another mesh erosion on the contralateral side. This time, a
      complete vaginal resection of the mesh was performed. CONCLUSION: Intraoperative
      cystoscopy should be considered after a transobturator tape procedure. Bilateral
      mesh erosion may result from motion of a cystocele against a fixed transobturator
      tape. Concurrent repair of the cystocele to prevent future mesh erosions may be
      warranted.

PMID- 17018475
TI  - Obturator hematoma after the transobturator suburethral tape procedure.
AB  - BACKGROUND: Herein we report a case of obturator hematoma formation which
      occurred during our 25th case involving the transobturator suburethral tape
      procedure with the inside-to-out approach. CASE: A case of an obturator hematoma
      forming after a transobturator suburethral tape procedure is reported. The
      patient did not become infected and was managed conservatively. The hematoma
      spontaneously resorbed after 11 weeks and the patient was cured of her
      incontinence. CONCLUSION: The transobturator approach for suburethral tape
      placement may be associated with vascular complications.

PMID- 17018476
TI  - Complications after laparoscopic burch with hernia mesh and surgical tacks.
AB  - BACKGROUND: The Burch retropubic urethropexy for the repair of stress urinary
      incontinence can be performed laparoscopically. Advances in laparoscopic
      technique have led some surgeons to perform this procedure with hernia mesh and
      surgical tacks. CASE: A postmenopausal woman presented with complaints of lower
      abdominal pain, dyspareunia, dysuria, and urinary urgency and frequency after a
      laparoscopic Burch and paravaginal repair. Bimanual examination revealed
      tenderness over the pelvic floor muscles and anterior vaginal wall. Exploratory
      laparotomy revealed dense fibrous adhesions in the space of Retzius along with
      mesh, permanent suture, and 13 helical tacks. CONCLUSION: Laparoscopic procedures
      that use hernia mesh fastened with surgical tacks should not be used in the
      vagina or surrounding structures.

PMID- 17018477
TI  - Obturator abscess after transobturator tape for stress urinary incontinence.
AB  - BACKGROUND: A transobturator tape is a nonwoven, thermally bonded polypropylene
      tape recently approved in Europe for minimally invasive treatment of stress
      urinary incontinence. CASE: Three cases of obturator abscess after transobturator
      tape procedures are reported. Patients presented with groin pain and vaginal
      discharge, and physical examination showed vaginal erosions. Magnetic resonance
      imaging confirmed the obturator abscess. All patients had complete sling removal
      and were treated with antibiotics. The organism responsible for the obturator
      abscess was Bacteroides fragilis in all three cases, suggesting that the
      infection occurred through a vaginal erosion. CONCLUSION: Persistent painful or
      irritating symptoms after suburethral tape procedures may be due to a vaginal
      erosion that can be associated with an obturator abscess. Appropriate evaluation
      and treatment result in marked symptomatic improvement, although stress
      incontinence may recur.

PMID- 17018478
TI  - Oxytocin-associated rupture of an unscarred uterus in a primigravida.
AB  - BACKGROUND: Intrapartum rupture of the unscarred uterus is an uncommon event,
      usually associated with such risk factors as grand multiparity, malpresentation,
      history of gestational trophoblastic disease, or instrumented delivery. Rupture
      during first pregnancy is extremely rare. CASE: A 30-year-old primigravid woman
      was admitted for labor augmentation with oxytocin at 40.5 weeks of gestation. The
      oxytocin infusion rate was increased during the first and second stages of labor
      despite contractions occurring at a rate of 4-5 per 10 minutes. The uterus
      ruptured during second stage. Despite emergency cesarean delivery, the baby had
      evidence of severe asphyxia. CONCLUSION: This case of uterine rupture in a
      primigravida with no prior uterine surgery and a structurally normal uterus
      underscores the importance of careful contraction monitoring and judicious
      control of oxytocin infusion rates.

PMID- 17018479
TI  - Unexplained prelabor uterine rupture in a term primigravida.
AB  - BACKGROUND: Uterine rupture is a catastrophic obstetric complication. The main
      risk factor is a scarred uterus, usually secondary to a previous cesarean
      delivery. Uterine rupture in a primigravid woman is a very rare event. CASE: A 33
      year-old primigravida presented at term with severe abdominal pain, signs of
      hemodynamic instability, and fetal bradycardia. She was not in labor, and the
      fetal heart tones disappeared before a cesarean could be performed. After a
      failed attempt at induction, exploratory laparotomy was performed for worsening
      maternal hemodynamic status. A complete rupture of the posterior uterine wall was
      found with a well-grown fetus free in the abdominal cavity. The uterus was
      repaired in two layers, and the patient did well postoperatively. CONCLUSION: We
      report the rare occurrence of a spontaneous uterine rupture in a nonlaboring
      primigravid with no known risk factors. The differential diagnosis of this
      presentation includes concealed placental abruption, subhepatic hematoma with or
      without liver rupture, splenic rupture, rupture of the broad ligament, and
      rupture of a uterine vein. Although uterine rupture occurs more commonly in the
      multiparous population, it cannot be assumed that the primigravid uterus is
      immune to rupture.

PMID- 17018480
TI  - Primary vulvar nocardiosis.
AB  - BACKGROUND: Nocardiosis is an uncommon disease, and the primary skin infection is
      usually at the site of a recent injury. Nocardia is a saprophytic bacterium of
      the soil belonging to the order Actinomycetales. CASE: A 68-year-old woman
      presented with a painful, hard, dark reddish lesion located in the right
      hemivulva. She had been treated by radiotherapy for a vulvar leiomyosarcoma
      arising from the left Bartholin gland at the age of 45. Pathology results
      demonstrated nocardial infection, initially advanced despite antibiotic therapy.
      The necrosis extended to and involved the ischiopubic bone, requiring extensive
      surgical treatment. We performed a radical vulvectomy with partial pubic bone
      excision to remove the necrotic tissue. A transverse gracilis-myocutaneous free
      flap was used for vulvar reconstruction. Wound necrosis recurrence required a
      rectus abdominis myocutaneous flap reconstruction, with an excellent final
      result. CONCLUSION: This is the first report of primary vulvar nocardiosis. This
      infection may simulate advanced vulvar carcinoma requiring extensive surgical
      treatment.

PMID- 17018481
TI  - Dysembryoplastic neuroepithelial tumor in pregnancy.
AB  - BACKGROUND: Dysembryoplastic neuroepithelial tumor is a rare, low-grade brain
      tumor that is characterized by intractable, partial seizures of juvenile onset.
      CASE: A 36-year-old pregnant woman with dichorionic, diamniotic twins temporarily
      lost consciousness at 27 weeks of gestation. Magnetic resonance imaging
      evaluation showed a 3-cm multicystic nodule in her right temporal lobe that was
      diagnosed, together with her history of recurrent anxiety attacks, as
      dysembryoplastic neuroepithelial tumor. The lesion did not enlarge during
      pregnancy, and healthy male infants were delivered by cesarean at 36 weeks. The
      tumor was successfully removed 2 months postpartum, and the patient has
      experienced no further seizures. CONCLUSION: Dysembryoplastic neuroepithelial
      tumor was conservatively managed during pregnancy without neurosurgical
      intervention.

PMID- 17018482
TI  - Repair of uterocutaneous fistula.
AB  - BACKGROUND: Uterocutaneous fistula is a rare condition that may be difficult to
      manage. CASE: A young woman who underwent surgical intervention for
      cryptomenorrhea 3 years ago developed menstrual discharge from the abdominal
      scar. A fistulous tract leading from the infraumbilical midline scar to the
      uterus was demonstrated on contrast study. Genital examination revealed vaginal
      agenesis. A vaginoplasty was performed as the first stage. This was followed one
      year later by excision of the fistulous tract and establishment of cervicovaginal
      communication. The patient is now menstruating from the vaginal passage.
      CONCLUSION: This case shows that a stepwise, well-planned, and well-executed
      procedure can lead to a satisfactory repair of an uterocutaneous fistula.

PMID- 17018483
TI  - Rapid growth of a kidney angiomyolipoma after initiation of oral contraceptive
      therapy.
AB  - BACKGROUND: Kidney angiomyolipomas are benign but progressive tumors consisting
      of smooth muscle, fat, and vascular elements, commonly associated with the
      tuberous sclerosis complex. Angiomyolipomas express estrogen and progesterone
      receptors and have been reported to increase in size in pregnancy. CASE: A 15
      year-old girl with stable angiomyolipomas of tuberous sclerosis complex was
      treated for menorrhagia with estrogen/progestin oral contraceptive pills. During
      the 12 months of contraceptive therapy, a new 4-cm exophytic angiomyolipoma
      developed that required selective arterial embolization to reduce its risk of
      spontaneous rupture. CONCLUSION: Treating menorrhagia with exogenous hormonal
      therapy in women with tuberous sclerosis complex should be accompanied by regular
      renal imaging to reduce the risk of an unanticipated angiomyolipoma-related
      adverse event. Alternate nonhormonal therapies for menorrhagia may also be
      considered.

PMID- 17018484
TI  - Cervical neck dislocation associated with the Zavanelli maneuver.
AB  - BACKGROUND: In the management of shoulder dystocia, fetal head replacement into
      the uterus has been advocated should delivery attempts remain unsuccessful.
      Reports of the Zavanelli maneuver have been remarkably optimistic despite the
      challenges of the procedure. CASE: A gravida 3 para 2 (two previous vaginal
      deliveries of more than 4,500-g infants) with gestational diabetes presented at
      term. Following a low forceps delivery, shoulder dystocia was encountered and was
      unable to be relieved with standard maneuvers. A cesarean delivery was performed,
      shoulders disimpacted, and the infant delivered abdominally. A 4,680-g stillborn
      infant was delivered with radiologic and autopsy evidence of cervical C5-C6
      dislocation. CONCLUSION: Despite published reports of high success rates and
      limited fetal consequences, physicians should be aware of adverse consequences
      including cervical neck trauma associated with use of the Zavanelli maneuver.

PMID- 17018485
TI  - In utero losartan withdrawal and subsequent development of fetal inferior vena
      cava thrombosis.
AB  - BACKGROUND: Angiotensin receptor blockers are antihypertensive medications
      prescribed by a wide variety of physicians, especially for patients with
      coexistent diabetes mellitus. Angiotensin receptor blockers, as well as
      angiotensin-converting enzyme inhibitors, are contraindicated in pregnancy. CASE:
      We describe the reversal of losartan-induced oligohydramnios at 27 weeks of
      gestation with subsequent development of fetal thrombosis and possible mechanism
      of action for this extremely rare in utero complication. CONCLUSION: This theory
      may help explain the fetal stillbirths in women taking this class of medications
      during the second and third trimester of pregnancy.

PMID- 17018486
TI  - Night sweats and elevated follicle-stimulating hormone levels while taking
      selective serotonin reuptake inhibitors.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly
      prescribed to women with depression and anxiety disorders. Although night sweats
      are a reported adverse effect, some women have relief of vasomotor symptoms
      during perimenopausal period while taking them. The relationships between SSRIs,
      thermoregulation, gonadotropins, and estrogen and their connection to fertility
      remain unclear. CASE: A reproductive-aged woman, seeking treatment for
      infertility, experienced night sweats and elevated follicle-stimulating hormone
      levels while taking SSRIs for treatment of depression. CONCLUSION: Many women of
      reproductive age are taking SSRIs, but the affect of SSRIs on normal reproductive
      function is unknown and further research in this area is needed.

PMID- 17018487
TI  - Burkitt's lymphoma of the ovary in pregnancy.
AB  - BACKGROUND: Burkitt's lymphoma is a rapidly growing and, if untreated, rapidly
      fatal tumor derived from B-lymphocytes. The occurrence of Burkitt's lymphoma
      during pregnancy is rare. CASE: A patient with Burkitt's lymphoma presented at 12
      weeks of gestation with abdominal and tooth pain. An 11 x 11 x 15 cm mass was
      seen on abdominal/pelvic ultrasonogram. She underwent a left salpingo
      oophorectomy with removal of the mass, as well as a tooth extraction. The
      pathology examination confirmed lymphoma in the left ovary and in the tissue
      surrounding the extracted tooth. After surgical resection, she was treated with
      multiagent chemotherapy beginning at 13 4/7 weeks of gestation. At 39 weeks, she
      delivered a viable female infant weighing 2,270 g. CONCLUSION: The finding of an
      adnexal mass in conjunction with head and neck symptoms led to consideration of
      Burkitt's lymphoma. Prompt treatment with multiagent chemotherapy should be
      considered for pregnant patients with Burkitt's lymphoma.

PMID- 17018488
TI  - Arterial embolus during common iliac balloon catheterization at cesarean
      hysterectomy.
AB  - BACKGROUND: Placenta accreta is associated with significant maternal morbidity.
      Prophylactic iliac artery balloon placement has been described as a treatment
      adjunct to minimize maternal risk of excessive blood loss at hysterectomy. CASE:
      A 37-year-old multigravida presented at 37 weeks of gestation with a known
      placenta previa and suspected placenta accreta. Iliac artery balloon catheters
      were placed immediately before cesarean delivery. The balloons were inflated
      after the infant was delivered, and placental-site hemorrhage required a cesarean
      hysterectomy with a 1,500-mL blood loss. A left popliteal arterial thrombus
      diagnosed postoperatively required thromboembolectomy. The patient was discharged
      home on postoperative day 5 with no further sequelae. CONCLUSION: Prophylactic
      arterial balloon occlusion may be associated with risks unique to pregnant women.

PMID- 17018489
TI  - Synchronous primary endometrial and ovarian carcinoma in a patient with marantic
      endocarditis.
AB  - BACKGROUND: Nonbacterial thrombotic endocarditis (NBTE), or marantic
      endocarditis, is a rare form of endocarditis found in patients with advanced
      malignancy and collagen-vascular disorders. There is limited information about
      the clinical course of patients with NBTE because the majority of cases are found
      at the time of autopsy. CASE: A 38-year-old woman presented to the emergency
      department with recent onset of chest pain and fatigue. Initial evaluation
      revealed cardiac valvular disease, and the patient underwent aortic valve
      replacement. Final pathology revealed nonbacterial thrombotic endocarditis. A
      metastatic work-up revealed a complex pelvic mass and elevated CA 125. The
      patient underwent an exploratory laparotomy and was subsequently found to have
      synchronous primary endometrial and ovarian carcinoma. CONCLUSION: Nonbacterial
      thrombotic endocarditis is rare and carries a high mortality. This case is
      unusual in that the diagnosis of nonbacterial thrombotic endocarditis led to the
      diagnosis of a gynecologic malignancy.

PMID- 17018490
TI  - Effect of gonadotropin-releasing hormone agonist on a uterine arteriovenous
      malformation.
AB  - BACKGROUND: The effect of gonadotropin-releasing hormone agonist (GnRHa) on
      uterine arteriovenous malformations (AVM) is not well known. CASE: A 37-year-old
      woman with a previous cesarean was diagnosed as having a uterine AVM after a
      spontaneous abortion with massive vaginal bleeding. The AVM decreased in size
      from 5.1 x 3.8 cm to 1.4 x 1.0 cm after 6 months of therapy with a GnRHa. Uterine
      artery embolization conducted after the GnRH therapy resulted in complete
      disappearance of the AVM. The patient's menstrual cycles and ovulation resumed 3
      months after uterine artery embolization. CONCLUSION: Gonadotropin-releasing
      hormone agonist therapy reduced the size of the uterine AVM. Thus, GnRHa therapy
      may be useful for uterine AVM in situations where uterine artery embolization
      must be postponed.

PMID- 17018491
TI  - Adenosarcoma arising in inguinal endometriosis.
AB  - BACKGROUND: Adenosarcoma arising in inguinal endometriosis is a rare clinical
      entity. CASE: A 47-year-old nulligravida presented with a persistent and enlarged
      right groin mass. Sixteen years earlier she had undergone total abdominal
      hysterectomy and bilateral salpingo-oophorectomy for endometriosis and was placed
      on estrogen therapy. Surgical en bloc excision of the 12 x 4 cm inguinal mass
      revealed adenosarcoma arising in endometriosis. CONCLUSION: Although a rare
      entity, adenosarcoma arising in inguinal endometriosis should be included in the
      differential diagnosis for those patients with a history of endometriosis and
      chronic unopposed estrogen therapy who present with a groin mass.

PMID- 17018492
TI  - A modified technique to deliver the posterior arm in severe shoulder dystocia.
AB  - BACKGROUND: Posterior arm delivery resolves almost all cases of severe shoulder
      dystocia. However, if the posterior arm is extended or lies under the fetus's
      body, the usually described technique for its delivery may not be practicable.
      CASE: A young, multiparous woman with type II diabetes had a low-midcavity vacuum
      delivery. Severe shoulder dystocia was encountered. The usual maneuvers,
      including the usual technique described for delivery of the posterior arm, were
      unsuccessful. A modified technique for delivery of the posterior arm was used.
      CONCLUSION: Posterior axillary traction will deliver the posterior arm when it is
      not accessible by the usual technique.

PMID- 17018493
TI  - Factor VIIa in puerperal hemorrhage with disseminated intravascular coagulation.
AB  - BACKGROUND: [corrected] Puerperal hemorrhage associated with disseminated
      intravascular coagulation is a life-threatening obstetric emergency. Recombinant
      factor VIIa is a novel hemostatic agent, but more information concerning its
      dosage, efficacy, and safety is required. CASE: A primigravida developed
      preeclampsia complicated by disseminated intravascular coagulation and severe
      puerperal hemorrhage after an emergency cesarean at 35(+5) weeks of gestation.
      Two doses of recombinant factor VIIa controlled the hemorrhage without any
      thrombotic complications. CONCLUSION: Recombinant factor VIIa should be
      considered when conventional methods fail to control puerperal hemorrhage
      complicated by disseminated intravascular coagulation. A review of 17 similar
      cases treated with this hemostatic agent revealed that in 76% a single dose
      ranging from 16.7 to 120 microg/kg controlled bleeding. Guidelines are needed to
      help obstetricians use recombinant factor VIIa effectively in such emergencies.

PMID- 17018494
TI  - Retroperitoneal lymphangioleiomyoma mimicking ovarian tumor emerging after
      tamoxifen therapy.
AB  - BACKGROUND: Lymphangioleiomyomas are lymphatic masses that can be associated with
      lymphangioleiomyomatosis. They are usually associated with pulmonary involvement.
      CASE: A 44-year-old premenopausal woman with breast cancer treated with adjuvant
      tamoxifen presented with abdominal distension. A thoraco-abdominopelvic enhanced
      computed tomography scan showed a 22 x 21 x 12 cm well-encapsulated, complex
      pelvic mass. An ovarian cystadenocarcinoma was suspected. Surgery revealed a
      retroperitoneal mass that was removed with uterus and both adnexae. Histological
      and immunohistochemical studies diagnosed a lymphangioleiomyoma. Estrogen and
      progesterone receptors were positive on smooth muscle cells and human melanoma
      black 45 was negative. CONCLUSION: Isolated retroperitoneal lymphangioleiomyoma
      is rare and difficult to detect in the absence of pulmonary
      lymphangioleiomyomatosis. We speculate that tamoxifen treatment may play a role
      in the development of this benign tumor.

PMID- 17018495
TI  - Ascites, elevated CA 125, and a large adnexal mass with an enteroovarian fistula.
AB  - BACKGROUND: Rectovaginal and vesicovaginal fistulae occur commonly in human
      immunodeficiency virus (HIV)-positive women and typically present with a
      characteristic vaginal discharge. CASE: We report a case of a jejunal-ovarian
      fistula presenting as suspected malignancy in a 38-year-old woman with HIV. The
      patient presented with ascites, moderately elevated CA 125, and a 12-cm adnexal
      mass. She was expedited to surgery secondary to a persistent pelvic mass and the
      patient's desire for definitive treatment. We believe the patient's
      immunocompromised state caused a microperforation in the small bowel, which
      subsequently formed a fistula to the ovary. The patient's left adnexa was
      removed, along with a 3-cm portion of small bowel. CONCLUSION: Uncommon entities
      should be included in the differential diagnosis of pelvic masses in
      immunocompromised women.

PMID- 17018496
TI  - Fetal and maternal magnetocardiography during flecainide therapy for
      supraventricular tachycardia.
AB  - BACKGROUND: Fetal magnetocardiography is a noninvasive technique capable of
      identifying fetal arrhythmias and can simultaneously characterize the cardiac
      rhythm of the mother and fetus. CASES: Three patients, two singleton pregnancies
      and one twin pregnancy, were admitted for evidence of fetal supraventricular
      tachycardia. Fetal magnetocardiography was used to monitor the effects of
      flecainide therapy on the fetus and mother. Two singleton pregnancy fetuses
      showed improved heart rate and cardiac rhythm within 1 week of the initial
      dosing. Maintenance dosages controlled the conditions thereafter. Flecainide
      slowed the supraventricular tachycardia in the twin subject, but
      magnetocardiography revealed maternal adverse effects necessitating termination
      of flecainide therapy. CONCLUSION: Magnetocardiography is a valuable tool for
      rhythm diagnosis and for monitoring the maternal and fetal cardiac rhythms in a
      patient undergoing flecainide therapy for fetal supraventricular tachycardia.

PMID- 17018497
TI  - Removal of pelvic leiomyomata and endometriosis five years after supracervical
      hysterectomy.
AB  - BACKGROUND: The number of laparoscopic supracervical hysterectomies performed has
      increased, yet the benefits and consequences are not well understood. CASE: The
      patient presented 5 years after a laparoscopic supracervical hysterectomy with
      pelvic pain, an elevated CA 125 level, and a pelvic mass. Surgical exploration
      revealed multiple leiomyomata with adenomyosis and endometriosis. CONCLUSION:
      After a laparoscopic supracervical hysterectomy, pelvic seeding of morcellated
      uterine tissue may lead to symptomatic pelvic leiomyomata and endometriosis
      requiring further surgery. Surgeons performing laparoscopic supracervical
      hysterectomies should take measures to prevent pelvic seeding at the time of
      morcellation and recognize the complication when it occurs.

PMID- 17018498
TI  - Use of intrauterine device in the setting of uterus didelphys.
AB  - BACKGROUND: Uterine anomalies are frequently diagnosed in reproductive-aged women
      and are generally considered a contraindication to the use of intrauterine
      contraception. We elected to offer this method to a woman with uterus didelphys
      and a poorly controlled seizure disorder who wished to avoid hormonal and barrier
      contraceptives. CASE: A 17-year-old woman (gravida 1, para 1) with a seizure
      disorder desired an intrauterine device (IUD). She was found to have uterus
      didelphys and a complete vaginal septum. After obtaining informed consent, an IUD
      was placed in each uterine horn. The patient retained both IUDs and was satisfied
      with the method 9 months after IUD insertion. CONCLUSION: Intrauterine
      contraception should be considered an option for women with uterine anomalies on
      a case-by-case basis.

PMID- 17018499
TI  - Ectopic decidualization causing massive postpartum intraperitoneal hemorrhage.
AB  - BACKGROUND: Spontaneous intraperitoneal hemorrhage during pregnancy or in the
      postpartum period is a rare but dangerous phenomenon. CASE: A 41-year-old gravida
      3 para 1, 9 days postpartum, presented with lower abdominal pain and hypovolemia.
      Emergent laparotomy revealed massive intraperitoneal hemorrhage caused by ectopic
      decidualization with vascular intrusion into the left hypogastric artery in an
      area of previously documented endometriosis. CONCLUSION: Ectopic deciduosis is
      usually no more than a pathologic curiosity. In a pregnant patient with
      spontaneous intraperitoneal hemorrhage, however, it must be considered because it
      results in a high incidence of maternal and neonatal mortality.

PMID- 17018500
TI  - Inflammatory pseudotumor of pelvic lymph nodes.
AB  - BACKGROUND: Inflammatory pseudotumor is a rare benign cause of lymphadenopathy
      previously reported in several anatomic locations that can simulate malignant
      neoplasm. CASE: A postmenopausal woman presented with abdominal pain, generalized
      malaise, leukocytosis, and intermittent fevers up to 102 degrees F. A 5-day
      course of antibiotics was given with persistence of symptoms. Computed tomography
      of the abdomen and pelvis demonstrated an ill-defined, retroperitoneal soft
      tissue density, and lymphadenopathy. She underwent an exploratory laparotomy,
      total abdominal hysterectomy, bilateral salpingo-oophorectomy, and unilateral
      pelvic and paraaortic lymphadenotomy. Histologic examination revealed
      inflammatory pseudotumor of the lymph nodes, with immunohistochemical studies
      demonstrating actin-positive myofibroblastic cells. Four months after surgery,
      the patient remains asymptomatic without evidence of disease. CONCLUSION:
      Inflammatory pseudotumor of the pelvic lymph nodes is a rare entity and should be
      included in the differential diagnosis of patients with persistent fever and
      lymphadenopathy.

PMID- 17018501
TI  - Cavernous transformation of the portal vein complicating pregnancy.
AB  - BACKGROUND: Cavernous transformation of the portal vein, associated with varices
      and thrombocytopenia, rarely complicates pregnancy. CASE: A 20-year-old
      primigravida with cavernous transformation of the portal vein underwent wireless
      video esophageal capsule endoscopy at 28 weeks of gestation, which ruled out
      esophageal and gastric varices and the need for prophylactic sclerotherapy.
      Magnetic resonance angiography at 32 weeks of gestation showed no abdominal wall
      varices or abnormally dilated lumbar or extradural veins, which ensured a safe
      surgical approach for cesarean and preserved the patient's ability to receive
      regional anesthesia. CONCLUSION: New noninvasive imaging modalities aided
      evaluation and management of the gravida with cavernous transformation of the
      portal vein.

PMID- 17018502
TI  - Milk-alkali syndrome presenting as acute renal insufficiency during pregnancy.
AB  - BACKGROUND: Gastroesophageal reflux is common during pregnancy. Hypercalcemia
      from overuse of antacids can lead to complications, including the milk-alkali
      syndrome. CASE: A multiparous patient, at 35 weeks of gestation, was admitted to
      evaluate an unexplained increase in her serum creatinine (0.6 mg/dL to 1.4
      mg/dL). She was normotensive and asymptomatic. Her serum calcium was 16.2 mg/dL.
      She reported significant gastric reflux symptoms and was taking a calcium-based
      antacid at high doses. She was treated with aggressive hydration. Her calcium and
      renal function normalized with no further complications. CONCLUSION: Overuse of
      calcium-containing medications can cause milk-alkali syndrome. Vigorous hydration
      is generally adequate treatment, and education regarding calcium intake is
      important to prevent occurrence.

PMID- 17018503
TI  - Massive subchorionic hematoma associated with enoxaparin.
AB  - BACKGROUND: The use of low-molecular-weight heparins is increasing for the
      prevention of thromboembolism in pregnancy. Subchorionic hematoma as a
      complication of anticoagulation therapy is rarely reported. CASE: A persistent,
      massive subchorionic hematoma was diagnosed in a pregnant patient with atrial
      fibrillation and mitral stenosis. Enoxaparin was administered to maintain her
      trough anti-Xa level 0.5 units/mL or higher. The patient's peak anti-Xa levels
      never exceeded 1.05 units/mL. The patient underwent cesarean delivery at 34 6/7
      weeks of gestation for preterm premature rupture of membranes. CONCLUSION:
      Subchorionic hematoma is a potentially serious complication that can occur in
      pregnant patients receiving enoxaparin for the prevention of thromboembolism.

PMID- 17018504
TI  - Malignant hypercalcemia in pregnancy: effect of pamidronate on uterine
      contractions.
AB  - BACKGROUND: Hypercalcemia in pregnancy can have devastating effects on both
      mother and fetus. Pamidronate, a bisphosphonate and inhibitor of bone resorption,
      has been used to treat hypercalcemia, but it is considered contraindicated in
      pregnancy. CASE: A 40-year-old multigravida presented at 24 weeks of gestation
      with metastatic breast cancer. After unsuccessful chemotherapy, at 28 weeks of
      gestation she had deteriorating renal function, frequent contractions, and a
      calcium level of 17.6 mg/dL. When conventional treatment of hypercalcemia failed,
      pamidronate dramatically decreased both the calcium levels and the frequency of
      uterine contractions. CONCLUSION: Pamidronate in pregnancy successfully reduced
      severe maternal hypercalcemia and uterine contractions. Although the reduction in
      calcium level did not prevent the development of preeclampsia or further
      deterioration in the mother's condition, it was not associated with any adverse
      effects on the neonate.

PMID- 17018505
TI  - Extracorporeal membrane oxygenation in pregnancy.
AB  - BACKGROUND: Safety and efficacy of extracorporeal membrane oxygenation (ECMO) in
      pregnancy is unknown. CASE: A 33-year-old pregnant woman at 23 weeks of gestation
      presented with acute respiratory distress syndrome unresponsive to conventional
      mechanical ventilation. Early initiation of ECMO therapy along with protective
      mechanical ventilation strategy resulted in an excellent maternal and fetal
      outcome. CONCLUSION: Extracorporeal membrane oxygenation can be life saving when
      initiated early in pregnant patients with severe acute respiratory insufficiency
      unresponsive to conventional mechanical ventilation.

PMID- 17018506
TI  - Acute onset headache complicating labor epidural caused by intrapartum
      pneumocephalus.
AB  - BACKGROUND: Epidural placement for obstetric anesthesia is a common procedure.
      Pneumocephalus, the introduction of air into the cranial cavity after epidural
      placement, is a rare complication encountered when air is used for identification
      of the epidural space. CASE: A 42-year-old primipara undergoing epidural
      placement reported sudden onset of severe headache with associated neurologic
      symptoms and nuchal rigidity. Emergent CT scan revealed pneumocephalus. With
      conservative management, her symptoms resolved with interval resumption of the
      air collection evidenced on interval CT. CONCLUSION: Acute onset headache after
      epidural placement can present with impressive neurologic signs and symptoms.
      Prompt identification of the cause of this pathology is of vital importance to
      delineate pneumocephalus from potentially treatable or life-threatening
      disorders.

PMID- 17018507
TI  - Disseminated gonococcal infection in pregnancy presenting as meningitis and
      dermatitis.
AB  - BACKGROUND: In 2003, the reported gonorrhea rate among women was 118.8 per
      100,000 women. Most gonococcal infections in pregnant women are asymptomatic or
      produce a mildly symptomatic genital infection. Disseminated infections can occur
      when gonococcal bacteremia produces extragenital symptoms, most commonly
      arthritis. CASE: A patient presented in the third trimester of pregnancy with
      fever, body aches, neck soreness, and skin lesions. There was no arthritis.
      Cultures performed during evaluation confirmed extragenital Neisseria
      gonorrhoeae. CONCLUSION: A high index of suspicion is necessary to diagnose
      disseminated gonococcal infection and prevent disease sequelae.

PMID- 17018508
TI  - Endoscopic third ventriculostomy for the treatment of obstructive hydrocephalus
      during pregnancy.
AB  - BACKGROUND: Endoscopic third ventriculostomy is an effective procedure for
      treating obstructive (noncommunicating) hydrocephalus as an alternative to
      ventricular shunt placement. CASE: Five pregnant women undergoing endoscopic
      third ventriculostomy as treatment for newly diagnosed acute obstructive
      hydrocephalus (n=2) or in cases of malfunction of a preexisting
      ventriculoperitoneal shunt (n=3) are presented. CONCLUSION: Endoscopic third
      ventriculostomy may be preferred to ventricular shunt placement as the initial
      mode of treatment for pregnant patients with newly diagnosed obstructive
      hydrocephalus as well as in cases of malfunction of a preexisting shunt.

PMID- 17018509
TI  - Recognition and prevention of gastric injury during gynecologic laparoscopy.
AB  - BACKGROUND: Laparoscopy has become an essential tool for the gynecologist. Its
      use has dramatically increased, in part, because of technological advances, but
      also because of well-documented advantages over laparotomy in particular
      scenarios. Immediate recognition of a complication is essential for reducing
      morbidity and potential mortality. We report an inadvertent gastric injury during
      a diagnostic laparoscopy. CASE: A 36-year-old woman sustained a gastric
      perforation during the insertion of an umbilical 5-mm trocar. After the injury
      was recognized, the patient underwent exploratory laparotomy, and primary repair
      of the defect was performed. The patient had an uneventful postoperative
      recovery. CONCLUSION: Gastric injury is a rare complication of gynecologic
      laparoscopy. Identification of risk factors, the use of a nasogastric or
      orogastric tube to relieve any gastric dilatation before initiation of the
      procedure, and proper surgical technique may minimize such injuries.

PMID- 17018510
TI  - Vasospasm of the nipple presenting as painful lactation.
AB  - BACKGROUND: Breast pain is a common complaint among lactating women. Vasospasm of
      the nipple should be considered in the differential diagnosis of breast pain,
      particularly when no other signs of infection or trauma are encountered. This
      report demonstrates a case of vasospasm successfully treated with nifedipine.
      CASE: A 26-year-old breastfeeding multipara presented with intermittent episodes
      of extreme pain associated with blanching of the nipple. The pain subsided upon
      return of normal color to the nipple. She was able to continue breastfeeding
      after successful treatment with nifedipine. CONCLUSION: Vasospasm of the nipple
      causes severe episodic breast pain and may lead to discontinuation of
      breastfeeding if not appropriately treated. This phenomenon is not well reported
      in the obstetric and gynecologic literature, although the obstetrician may be the
      first physician to evaluate a patient with symptoms. Patients with episodic
      nipple pain and pallor can be successfully treated with nifedipine.

PMID- 17018511
TI  - Persistent postpartum headache from a chronic subdural hematoma after peridural
      anesthesia.
AB  - BACKGROUND: Postpartum headache after peridural anesthesia is usually attributed
      to accidental perforation of the dura causing postlumbar puncture headache. CASE:
      In a patient with persistent headache after peridural anesthesia for labor, a
      chronic subdural hematoma was diagnosed 5 weeks postpartum. CONCLUSION: Caution
      is warranted in patients with peridural anesthesia for labor who present with
      unusually persistent headache.

PMID- 17018512
TI  - Severe vaginal pain caused by a neuroma in the rectovaginal septum after
      posterior colporrhaphy.
AB  - BACKGROUND: Traumatic vaginal neuromas are a rarely documented finding in the
      setting of vaginal pain after posterior colporrhaphy. They arise as a result of
      trauma or surgery and are often mistaken for scar tissue. CASE: After a total
      vaginal hysterectomy and posterior colporrhaphy, a 32-year-old woman presented
      with debilitating vaginal pain, presumed to be secondary to scar tissue
      formation. Excision of the tissue from the rectovaginal septum revealed a
      traumatic neuroma. After the removal of the neuroma, the patient's vaginal pain
      resolved. CONCLUSION: Traumatic neuromas may be a cause of significant point
      tenderness and thickened tissue after vaginal surgery or repair of obstetric
      lacerations. If conservative treatment methods have failed, surgical excision of
      the neuroma can be considered.

PMID- 17018513
TI  - Abdominal radical trachelectomy during pregnancy to preserve pregnancy and
      fertility.
AB  - BACKGROUND: For 10,000-40,000 women each year, cervical cancer complicates
      pregnancy. Current therapy usually terminates the pregnancy and results in the
      loss of future fertility. Abdominal radical trachelectomy is a fertility
      preserving alternative to radical hysterectomy for young women with cervical
      cancer. CASES: We report five pregnancies complicated by cervical cancer treated
      by abdominal radical trachelectomy with preservation of the concurrent pregnancy
      and the birth of two healthy term infants. CONCLUSION: Pregnancy complicated by
      concurrent cervical cancer can be managed with abdominal radical trachelectomy
      during pregnancy while preserving future fertility.

PMID- 17018514
TI  - Lymphocytic myocarditis presenting as nausea, vomiting, and hepatic dysfunction
      in the first trimester of pregnancy.
AB  - BACKGROUND: Lymphocytic myocarditis, an immune disorder of left ventricular
      dysfunction with sometimes confounding clinical presentations, occurs rarely
      during pregnancy. CASE: At 12 weeks gestation, a multigravid patient presented
      with a 2-month history of nausea and vomiting. Other symptomatology included
      postprandial epigastric pain, loose stools, and a 10-lb (4.5-kg) weight loss.
      Laboratory evaluation revealed evidence of hepatic dysfunction with a
      coagulopathy and an absolute unconjugated hyperbilirubinemia. While undergoing
      evaluation, the patient deteriorated rapidly and suffered a cardiopulmonary
      arrest. Autopsy revealed a congested liver and spleen associated with a dilated
      cardiomyopathy and lymphocytic myocarditis. CONCLUSION: Medically virulent
      disease processes can mimic the common pregnancy complaint of nausea and
      vomiting. Intrinsic cardiac disease with secondary hepatic compromise is a rare
      cause of gastrointestinal symptomatology early in pregnancy.

PMID- 17018515
TI  - Thrombotic thrombocytopenic purpura masquerading as hemolysis, elevated liver
      enzymes, low platelets (HELLP) syndrome in late pregnancy.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura rarely presents during late
      pregnancy or immediately postpartum. This report describes the clinical course of
      a patient considered to have hemolysis, elevated liver enzymes, low platelets
      (HELLP) syndrome but later determined to have thrombotic thrombocytopenic
      purpura. CASE: At 37 weeks of gestation, a multiparous woman was diagnosed with
      HELLP syndrome. She received high-dose dexamethasone, magnesium,
      antihypertensives, and platelets before delivery. Over the next 36 hours, renal
      function acutely worsened and death ensued. One week after death a plasma
      ADAMTS13 activity of 4% was reported. CONCLUSION: Thrombotic thrombocytopenic
      purpura can mimic HELLP syndrome late in gestation. Lack of response to
      dexamethasone within 12-24 hours and atypical relationships among laboratory
      values are two clues that thrombotic thrombocytopenic purpura may be the
      underlying pathology and that plasma exchange is emergently needed.

PMID- 17018516
TI  - Uterine torsion and fetal bradycardia associated with external cephalic version.
AB  - BACKGROUND: Torsion of the gravid uterus is a rare obstetric complication in
      humans, but has been reported in association with malpresentation and with
      uterine leiomyomata. CASE: We report a case of uterine torsion diagnosed at
      emergency cesarean delivery after external cephalic version with prolonged fetal
      bradycardia. CONCLUSION: Physicians should be aware of the possibility of uterine
      torsion as a complication of external cephalic version. To minimize diagnostic
      delay, placental localization on ultrasonography should be noted before and after
      external cephalic version as an indicator of uterine orientation.

PMID- 17018517
TI  - Mouse SNPs for evolutionary biology: beware of ascertainment biases.

PMID- 17018518
TI  - Regions of high differentiation--worth a check.
AB  - B. Boursot and K. Belkhir in this issue of Genome Research point to an
      ascertainment bias in my use of SNPs to identify regions of high differentiation
      between a pair of house mouse subspecies. Here, I discuss additional points to
      consider and argue that the ultimate test for such regions should be an
      independent confirmation using unrelated samples. I provide evidence that regions
      of high differentiation as identified from laboratory strains and potentially
      biased SNP markers can be confirmed and therefore are worth a deeper
      investigation.

PMID- 17018519
TI  - Secretome of primary cultures of human adipose-derived stem cells: modulation of
      serpins by adipogenesis.
AB  - Studies of adipogenic protein induction have led to a new appreciation of the
      role of adipose tissue as an endocrine organ. Adipocyte-derived "adipokines" such
      as adiponectin, leptin, and visceral adipose tissue-derived serine protease
      inhibitor (vaspin) exert hormone-like activities at the systemic level. In this
      study, we examined the secretome of primary cultures of human subcutaneous
      adipose-derived stem cells as an in vitro model of adipogenesis. Conditioned
      media obtained from four individual female donors after culture in uninduced or
      adipogenic induced conditions were compared by two-dimensional gel
      electrophoresis and tandem mass spectrometry. Over 80 individual protein features
      showing > or =2-fold relative differences were examined. Approximately 50% of the
      identified proteins have been described previously in the secretome of murine 3T3
      L1 preadipocytes or in the interstitial fluid derived from human mammary gland
      adipose tissue. As reported by others, we found that the secretome included
      proteins such as actin and lactate dehydrogenase that do not display a leader
      sequence or transmembrane domain and are classified as "cytoplasmic" in origin.
      Moreover we detected a number of established adipokines such as adiponectin and
      plasminogen activator inhibitor 1. Of particular interest was the presence of
      multiple serine protease inhibitors (serpins). In addition to plasminogen
      activator inhibitor 1, these included pigment epithelium-derived factor
      (confirmed by Western immunoblot), placental thrombin inhibitor, pregnancy zone
      protein, and protease C1 inhibitor. These findings, together with the recent
      identification of vaspin, suggest that the serpin protein family warrants further
      proteomics investigation with respect to the etiology of obesity and type 2
      diabetes.

PMID- 17018520
TI  - Improved validation of peptide MS/MS assignments using spectral intensity
      prediction.
AB  - A major limitation in identifying peptides from complex mixtures by shotgun
      proteomics is the ability of search programs to accurately assign peptide
      sequences using mass spectrometric fragmentation spectra (MS/MS spectra). Manual
      analysis is used to assess borderline identifications; however, it is error-prone
      and time-consuming, and criteria for acceptance or rejection are not well
      defined. Here we report a Manual Analysis Emulator (MAE) program that evaluates
      results from search programs by implementing two commonly used criteria: 1)
      consistency of fragment ion intensities with predicted gas phase chemistry and 2)
      whether a high proportion of the ion intensity (proportion of ion current (PIC))
      in the MS/MS spectra can be derived from the peptide sequence. To evaluate
      chemical plausibility, MAE utilizes similarity (Sim) scoring against theoretical
      spectra simulated by MassAnalyzer software (Zhang, Z. (2004) Prediction of low
      energy collision-induced dissociation spectra of peptides. Anal. Chem. 76, 3908
      3922) using known gas phase chemical mechanisms. The results show that Sim scores
      provide significantly greater discrimination between correct and incorrect search
      results than achieved by Sequest XCorr scoring or Mascot Mowse scoring, allowing
      reliable automated validation of borderline cases. To evaluate PIC, MAE
      simplifies the DTA text files summarizing the MS/MS spectra and applies heuristic
      rules to classify the fragment ions. MAE output also provides data mining
      functions, which are illustrated by using PIC to identify spectral chimeras,
      where two or more peptide ions were sequenced together, as well as cases where
      fragmentation chemistry is not well predicted.

PMID- 17018521
TI  - The role of hypothalamic malonyl-CoA in energy homeostasis.
AB  - Energy balance is monitored by hypothalamic neurons that respond to peripheral
      hormonal and afferent neural signals that sense energy status. Recent
      physiologic, pharmacologic, and genetic evidence has implicated malonyl-CoA, an
      intermediate in fatty acid synthesis, as a regulatory component of this energy
      sensing system. The level of malonyl-CoA in the hypothalamus is dynamically
      regulated by fasting and feeding, which alter subsequent feeding behavior. Fatty
      acid synthase (FAS) inhibitors, administered systemically or
      intracerebroventricularly to lean or obese mice, increase hypothalamic malonyl
      CoA leading to the suppression of food intake. Conversely, lowering malonyl-CoA
      with an acetyl-CoA carboxylase (ACC) inhibitor or by the ectopic expression of
      malonyl-CoA decarboxylase in the hypothalamus increases food intake and reverses
      inhibition by FAS inhibitors. Physiologically, the level of hypothalamic malonyl
      CoA appears to be determined through phosphorylation/dephosphorylation of ACC by
      AMP kinase in response to changes in the AMP/ATP ratio, an indicator of energy
      status. Recent evidence suggests that the brain-specific carnitine:palmitoyl-CoA
      transferase-1 (CPT1c) may be a regulated target of malonyl-CoA that relays the
      "malonyl-CoA signal" in hypothalamic neurons that express the orexigenic and
      anorexigenic neuropeptides that regulate food intake and peripheral energy
      expenditure. Together these findings support a role for malonyl-CoA as an
      intermediary in the control of energy homeostasis.

PMID- 17018522
TI  - Stage-specific effects of cAMP signaling during distal lung epithelial
      development.
AB  - cAMP signaling is postulated to play a role in distal lung epithelial
      differentiation based on several observations. First, it enhances fibroblast
      growth factor-induced transdifferentiation of early tracheal epithelium into
      respiratory epithelium. Second, there are cAMP-responsive elements in the
      heterologous promoters of Sftpb and Sftpa genes. Third, cAMP augments the effect
      of dexamethasone in maintaining differentiation of human fetal type II pneumocyte
      culture. However, this concept has not been thoroughly tested in vivo. In the
      current study, we modulated cAMP signaling in developing distal lung epithelium
      in vivo using an inducible transgenic system that expressed a mutant form of
      Galpha(s) (Galpha(s)Q227L). We failed to demonstrate the ability of cAMP to
      promote distal epithelial maturation during embryonic stages. The results argue
      against its physiological role in this process. In addition, induction of cAMP
      signaling at the late pseudoglandular stage but not during the canalicular or
      saccular stage surprisingly delayed distal differentiation by suppressing the
      expression of Sftpc, Sftpa, and Aquaporin5 as well as the formation of lamellar
      bodies. This stage-specific inhibitory effect was observed in the absence of
      cellular toxicity or changes in branching. Transgenic lungs did not show
      significant changes in the known pathways that are important for distal
      differentiation. Therefore, we propose the existence of yet-to-be identified cAMP
      sensitive novel regulators of early distal lung epithelial differentiation.
      Although the delay of differentiation seemed to be reversible at later stages, it
      still led to pronounced permanent postnatal airspace enlargement due to impaired
      paracrine function of distal epithelium in regulating alveolar myofibroblast
      development.

PMID- 17018523
TI  - Study of claudin function by RNA interference.
AB  - Claudins are tight junction proteins that play a key selectivity role in the
      paracellular conductance of ions. Numerous studies of claudin function have been
      carried out using the overexpression strategy to add new claudin channels to an
      existing paracellular protein background. Here, we report the systematic
      knockdown of endogenous claudin gene expression in Madin-Darby canine kidney
      (MDCK) cells and in LLC-PK1 cells using small interfering RNA against claudins 1
      4 and 7. In MDCK cells (showing cation selectivity), claudins 2, 4, and 7 are
      powerful effectors of paracellular Na+ permeation. Removal of claudin-2 depressed
      the permeation of Na+ and resulted in the loss of cation selectivity. Loss of
      claudin-4 or -7 expression elevated the permeation of Na+ and enhanced the
      proclivity of the tight junction for cations. On the other hand, LLC-PK1 cells
      express little endogenous claudin-2 and show anion selectivity. In LLC-PK1 cells,
      claudin-4 and -7 are powerful effectors of paracellular Cl- permeation. Knockdown
      of claudin-4 or -7 expression depressed the permeation of Cl- and caused the
      tight junction to lose the anion selectivity. In conclusion, claudin-2 functions
      as a paracellular channel to Na+ to increase the cation selectivity of the tight
      junction; claudin-4 and -7 function either as paracellular barriers to Na+ or as
      paracellular channels to Cl-, depending upon the cellular background, to decrease
      the cation selectivity of the tight junction.

PMID- 17018524
TI  - SRC tail phosphorylation is limited by structural changes in the regulatory
      tyrosine kinase Csk.
AB  - Src family tyrosine kinases are down-regulated through phosphorylation of a
      single C-terminal tyrosine by the nonreceptor tyrosine kinase Csk. Despite the
      fundamental role of Csk in controlling cell growth and differentiation, it is
      unclear what limits this key signaling reaction and controls the production of
      catalytically repressed Src. To investigate this issue, stopped-flow fluorescence
      experiments were performed to determine which steps modulate catalysis. Both Src
      binding and phosphorylation can be monitored by changes in intrinsic tryptophan
      fluorescence. Association kinetics are biphasic with the initial phase
      corresponding to the bimolecular interaction of both proteins and the second
      phase representing a slow conformational change that coincides with the rate of
      maximum turnover. The kinetic transients for the phosphorylation reaction are
      also biphasic with the initial phase corresponding to the rapid phosphorylation
      and the release of phospho-Src. These data, along with equilibrium sedimentation
      and product inhibition experiments, suggest that steps involving Src association,
      phosphorylation, and product release are fast and that a structural change in Csk
      participates in limiting the catalytic cycle.

PMID- 17018526
TI  - The presence of sarcolipin results in increased heat production by Ca(2+)-ATPase.
AB  - Skeletal muscle sarcoplasmic reticulum of large mammals such as rabbit contains
      sarcolipin (SLN), a small peptide with a single transmembrane alpha-helix. When
      reconstituted with the Ca(2+)-ATPase from skeletal muscle sarcoplasmic reticulum
      into sealed vesicles, the presence of SLN leads to a reduced level of
      accumulation of Ca(2+). Heats of reaction of the reconstituted Ca(2+)-ATPase with
      ATP were measured using isothermal calorimetry. The heat released increased
      linearly with time over 30 min and increased with increasing SLN content. Rates
      ATP hydrolysis by the reconstituted Ca(2+)-ATPase were constant over a 30-min
      time period and were the same when measured in the presence or absence of an ATP
      regenerating system. The calculated values of heat released per mol of ATP
      hydrolyzed increased with increasing SLN content and fitted to a simple binding
      equation with a dissociation constant for the SLN.ATPase complex of 6.9 x 10(-4)
      +/- 2.9 x 10(-4) in units of mol fraction per monolayer. It is suggested that the
      interaction between Ca(2+)-ATPase and SLN in the sarcoplasmic reticulum could be
      important in thermogenesis by the sarcoplasmic reticulum.

PMID- 17018525
TI  - The NH2-terminal propeptide of type I procollagen acts intracellularly to
      modulate cell function.
AB  - The function of the NH(2)-terminal propeptide of type I procollagen (N
      propeptide) is poorly understood. We now show that a recombinant trimeric N
      propeptide interacts with transforming growth factor-beta1 and BMP2 and exhibits
      functional effects in stably transfected cells. The synthesis of N-propeptide by
      COS-7 cells results in an increase in phosphorylation of Akt and Smad3 and is
      associated with a marked reduction in type I procollagen synthesis and impairment
      in adhesion. In C2C12 cells, N-propeptide inhibits the osteoblastic
      differentiation induced by BMP2. Our data suggest that these effects are mediated
      by the interaction of N-propeptide with an intracellular receptor in the
      secretory pathway, because they are not observed when recombinant N-propeptide is
      added to the culture medium of either COS-7 or C2C12 cells. Both the binding of N
      propeptide to cytokines and its functional properties are entirely dependent on
      the exon 2-encoded globular domain, and a mutation that substitutes a serine for
      a highly conserved cysteine in exon 2 abolishes its function. Our findings
      suggest that N-propeptide performs an important feedback regulatory function and
      provides a rationale for the prominence of a homotrimeric form of type I
      procollagen (alpha1 trimer) during vertebrate development.

PMID- 17018527
TI  - Evidence for a pre-latent form of the serpin plasminogen activator inhibitor-1
      with a detached beta-strand 1C.
AB  - Latency transition of plasminogen activator inhibitor-1 (PAI-1) occurs
      spontaneously in the absence of proteases and results in stabilization of the
      molecule through insertion of its reactive center loop (RCL) as a strand in beta
      sheet A and detachment of beta-strand 1C (s1C) at the C-terminal hinge of the
      RCL. This is one of the largest structural rearrangements known for a folded
      protein domain without a concomitant change in covalent structure. Yet, the
      sequence of conformational changes during latency transition remains largely
      unknown. We have now mapped the epitope for the monoclonal antibody H4B3 to the
      cleft revealed upon s1C detachment and shown that H4B3 inactivates recombinant
      PAI-1 in a time-dependent manner. With fluorescence spectroscopy, we show that
      insertion of the RCL is accelerated in the presence of H4B3, demonstrating that
      the loss of activity is the result of latency transition. Considering that the
      epitope for H4B3 appears to be occluded by s1C in active PAI-1, this finding
      suggests the existence of a pre-latent conformation on the path from active to
      latent PAI-1 characterized by at least partial detachment of s1C. Functional
      characterization of mutated PAI-1 variants suggests that a salt-bridge between
      Arg273 and Asp224 may stabilize the pre-latent conformation. The binding of H4B3
      and of a peptide targeting the cleft revealed upon s1C detachment was hindered by
      the glycans attached to Asn267. Conclusively, we have provided evidence for the
      existence of an equilibrium between active PAI-1 and a pre-latent form,
      characterized by reversible detachment of s1C and formation of a glycan-shielded
      cleft in the molecule.

PMID- 17018528
TI  - Negative regulation of osteoclastogenesis by ectodomain shedding of receptor
      activator of NF-kappaB ligand.
AB  - Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein
      that has an essential role in the development of osteoclasts. The extracellular
      portion of RANKL is cleaved proteolytically to produce soluble RANKL, but
      definite RANKL sheddase(s) and the physiologic function of RANKL shedding have
      not yet been determined. In the present study, we found that matrix
      metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have
      strong RANKL shedding activity. In Western blot analysis, soluble RANKL was
      detected as two different molecular weight products, and RNA interference of
      MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular
      weight products. Suppression of MMP14 in primary osteoblasts increased membrane
      bound RANKL and promoted osteoclastogenesis in cocultures with macrophages.
      Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly
      reduced, and their osteoclastogenic activity was promoted, consistent with the
      findings of increased osteoclastogenesis in vivo. RANKL shedding is an important
      process that down-regulates local osteoclastogenesis.

PMID- 17018530
TI  - A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3)
      functions as an amine oxidase with substrate specificity.
AB  - The human lysyl oxidase-like 3 (LOXL3) encodes a member of the emerging family of
      lysyl oxidase (LOX) that functions as a copper-dependent amine oxidase. The LOXL3
      protein contains four scavenger receptor cysteine-rich domains in the N terminus
      in addition to the C-terminal characteristic domains of the LOX family, such as a
      copper binding domain, a cytokine receptor-like domain and residues for the lysyl
      tyrosyl quinone cofactor. Using BLASTN searches, we identified a LOXL3 variant
      LOXL3-sv1 that lacked the sequences corresponding to exons 1, 2, 3, and 5 of
      LOXL3. LOXL3-sv1 showed an exon-intron structure distinct from LOXL3,
      additionally containing an 80-bp sequence corresponding to intron 3 of LOXL3 in
      the 5'-UTR and a 561-bp sequence corresponding to the 3'-flanking genomic region
      of exon 14 in the 3'-UTR. LOXL3-sv1 was predicted to encode a polypeptide of 392
      amino acids that contains the C-terminal domains required for amine oxidase
      activity but lacks the N-terminal SRCR domains 1, 2, and 3. The recombinant LOXL3
      sv1 protein showed a beta-aminopropionitrile-inhibitable amine oxidase activity
      toward elastin and collagen with substrate specificity. In RT-PCR assays with
      various human tissues, LOXL3-sv1 and LOXL3 showed distinct expression patterns.
      Further, luciferase reporter assays revealed a strong promoter element in intron
      3 that probably functions as a regulatory region for the expression of LOXL3-sv1.
      These findings strongly indicate that LOXL3 encodes two variants, LOXL3 and LOXL3
      sv1, both of which function as amine oxidases with distinct tissue and substrate
      specificities from one another.

PMID- 17018529
TI  - Regulation of the platelet-derived growth factor receptor-beta by G protein
      coupled receptor kinase-5 in vascular smooth muscle cells involves the
      phosphatase Shp2.
AB  - Smooth muscle cell (SMC) proliferation and migration are substantially controlled
      by the platelet-derived growth factor receptor-beta (PDGFRbeta), which can be
      regulated by the Ser/Thr kinase G protein-coupled receptor kinase-2 (GRK2). In
      mouse aortic SMCs, however, we found that prolonged PDGFRbeta activation
      engendered down-regulation of GRK5, but not GRK2; moreover, GRK5 and PDGFRbeta
      were coordinately up-regulated in SMCs from atherosclerotic arteries. With SMCs
      from GRK5 knock-out and cognate wild type mice (five of each), we found that
      physiologic expression of GRK5 increased PDGF-promoted PDGFRbeta seryl
      phosphorylation by 3-fold and reduced PDGFRbeta-promoted phosphoinositide
      hydrolysis, thymidine incorporation, and overall PDGFRbeta tyrosyl
      phosphorylation by approximately 35%. Physiologic SMC GRK5 activity also
      increased PDGFRbeta association with the phosphatase Shp2 (8-fold), enhanced
      phosphorylation of PDGFRbeta Tyr(1009) (the docking site for Shp2), and reduced
      phosphorylation of PDGFRbeta Tyr(1021). Consistent with having increased
      PDGFRbeta-associated Shp2 activity, GRK5-expressing SMCs demonstrated greater
      PDGF-induced Src activation than GRK5-null cells. GRK5-mediated desensitization
      of PDGFRbeta inositol phosphate signaling was diminished by Shp2 knock-down or
      impairment of PDGFRbeta/Shp2 association. In contrast to GRK5, physiologic GRK2
      activity did not alter PDGFRbeta/Shp2 association. Finally, purified GRK5
      effected agonist-dependent seryl phosphorylation of partially purified
      PDGFRbetas. We conclude that GRK5 mediates the preponderance of PDGF-promoted
      seryl phosphorylation of the PDGFRbeta in SMCs, and, through mechanisms involving
      Shp2, desensitizes PDGFRbeta inositol phosphate signaling and enhances PDGFRbeta
      triggered Src activation.

PMID- 17018531
TI  - NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple
      glycoforms that bind a variety of sterols.
AB  - Niemann-Pick C disease is a fatal neurodegenerative disorder characterized by an
      endolysosomal accumulation of cholesterol and other lipids. One form of the
      disease is caused by a deficiency in NPC2, a soluble lysosomal glycoprotein that
      binds cholesterol. To better understand the biological function of NPC2 and how
      its deficiency results in disease, we have characterized the structural and
      functional properties of recombinant human protein. Highly purified NPC2 consists
      of a complex mixture of glycosylated isoforms, similar to that observed in human
      brain autopsy specimens. Mass spectrometric analysis revealed that of the three
      potential N-linked glycosylation sites present in the mature protein, Asn-19 is
      not utilized; Asn-39 is linked to an endoglycosidase H (Endo H)-sensitive
      oligosaccharide, and Asn-116 is variably utilized, either being unmodified or
      linked to Endo H-sensitive or Endo H-resistant oligosaccharides. All glycoforms
      are endocytosed and ameliorate the cholesterol storage phenotype of NPC2
      deficient fibroblasts. In addition, the purified preparation contains a mixture
      of both free and lipid-bound protein. All glycoforms bind cholesterol, and sterol
      binding to NPC2 significantly alters its behavior upon cation-exchange
      chromatography. Based on this observation, we developed chromatography-based
      binding assays and determined that NPC2 forms an equimolar complex with the
      fluorescent cholesterol analog dehydroergosterol. In addition, we find that NPC2
      binds a range of cholesterol-related molecules (cholesterol precursors, plant
      sterols, some oxysterols, cholesterol sulfate, cholesterol acetate, and 5-alpha
      cholestan-3-one) and that 27-hydroxysterol accumulates in NPC2-deficient mouse
      liver. Binding was not detected for various glycolipids, phospholipids, or fatty
      acids. These biochemical properties support a direct and specialized function of
      NPC2 in lysosomal sterol transport.

PMID- 17018532
TI  - Two conserved residues govern the salt and pH dependencies of the binding
      reaction of a PDZ domain.
AB  - PDZ domains are protein-protein interaction modules found in hundreds of human
      proteins. Their binding reactions are sensitive to variations in salt and pH but
      the basis of the respective dependence has not been clear. We investigated the
      binding reaction between PSD-95 PDZ3 and a peptide corresponding to a native
      ligand with protein engineering in conjunction with stopped-flow and equilibrium
      fluorimetry and found that the two conserved residues Arg-318 and His-372 were
      responsible for the salt and pH dependencies, respectively. The basis of the salt
      dependent variation of the affinity was explored by mutating all charged residues
      in and around the peptide-binding pocket. Arg-318 was found to be crucial, as
      mutation to alanine obliterated the effect of chloride on the binding constants.
      The direct interaction of chloride with Arg-318 was demonstrated by time-resolved
      urea denaturation experiments, where the Arg-318 --> Ala mutant was less
      stabilized by addition of chloride as compared with wild-type PDZ3. We also
      demonstrated that protonation of His-372 was responsible for the increase of the
      equilibrium dissociation constant at low pH. Both chloride concentration and pH
      (during ischemia) vary in the postsynaptic density, where PSD-95 is present, and
      the physiological buffer conditions may thus modulate the interaction between PSD
      95 and its ligands through binding of chloride and protons to the "molecular
      switches" Arg-318 and His-372, respectively.

PMID- 17018533
TI  - Morphological and glycosylation changes associated with the endometrium and
      ectopic lesions in a baboon model of endometriosis.
AB  - BACKGROUND: Endometriosis is one of the most common causes of infertility and
      pelvic pain. A baboon model has recently been developed whereby the intrapelvic
      injection of menstrual endometrium results in the induction of endometriotic
      lesions. We have used this model to investigate changes in ultrastructure and
      glycosylation of endometria from normal and diseased baboons. METHODS:
      Endometriosis was induced in eight female baboons; endometrial tissue and
      endometriotic lesions were removed on days 9-11 post ovulation between 3 and 16
      months of disease and compared with endometrium from 17 control animals, using
      electron microscopy and lectin histochemistry. RESULTS: Ultrastructurally,
      diseased endometrial glands showed abnormalities in secretory vacuoles and an
      intracellular accumulation of glycogen; in later stages of the disease, glands
      resembled those of the late secretory phase endometrium. The abnormalities were
      mirrored by changes in glycan expression. In early disease, there was an
      increased binding of lectin from Dolichos biflorus agglutinin (DBA) to
      fucosylated N-acetylglucosamine residues, whereas in later stages, this binding
      generally decreased in association with the appearance of a late secretory
      phenotype. CONCLUSIONS: Endometriosis is accompanied by progressive changes in
      the gland architecture and biochemistry resulting in dyssynchrony within the
      window of uterine receptivity, which may result in the reduced fertility
      associated with this disease.

PMID- 17018534
TI  - GenoProfiler: batch processing of high-throughput capillary fingerprinting data.
AB  - High-throughput content fingerprinting techniques employing capillary
      electrophoresis place new demands on the editing of fingerprint files for the
      downstream contig assembly program, FPC. A cross-platform software application,
      GenoProfiler, was developed for automated editing of sized fingerprinting
      profiles generated by the ABI Genetic Analyzers. The batch-processing module
      extracts the sized fragment information directly from the ABI raw trace files, or
      from data files exported from GeneMapper or other size calling software, removes
      the background noise and undesired fragments, and generates fragment size files
      compatible with the FPC software. AVAILABILITY:
      http://wheat.pw.usda.gov/PhysicalMapping/

PMID- 17018535
TI  - ProtBuD: a database of biological unit structures of protein families and
      superfamilies.
AB  - MOTIVATION: Modeling of protein interactions is often possible from known
      structures of related complexes. It is often time-consuming to find the most
      appropriate template. Hypothesized biological units (BUs) often differ from the
      asymmetric units and it is usually preferable to model from the BUs. RESULTS:
      ProtBuD is a database of BUs for all structures in the Protein Data Bank (PDB).
      We use both the PDBs BUs and those from the Protein Quaternary Server. ProtBuD is
      searchable by PDB entry, the Structural Classification of Proteins (SCOP)
      designation or pairs of SCOP designations. The database provides the asymmetric
      and BU contents of related proteins in the PDB as identified in SCOP and Position
      Specific Iterated BLAST (PSI-BLAST). The asymmetric unit is different from PDB
      and/or Protein Quaternary Server (PQS) BUs for 52% of X-ray structures, and the
      PDB and PQS BUs disagree on 18% of entries. AVAILABILITY: The database is
      provided as a standalone program and a web server from
      http://dunbrack.fccc.edu/ProtBuD.php.

PMID- 17018536
TI  - Sungear: interactive visualization and functional analysis of genomic datasets.
AB  - Sungear is a software system that supports a rapid, visually interactive and
      biologist-driven comparison of large datasets. The datasets can come from
      microarray experiments (e.g. genes induced in each experiment), from comparative
      genomics (e.g. genes present in each genome) or even from non-biological
      applications (e.g. demographics or baseball statistics). Sungear represents
      multiple datasets as vertices in a polygon. Each possible intersection among the
      sets is represented as a circle inside the polygon. The position of the circle is
      determined by the position of the vertices represented in the intersection and
      the area of the circle is determined by the number of elements in the
      intersection. Sungear shows which Gene Ontology terms are over-represented in a
      subset of circles or anchors. The intuitive Sungear interface has enabled
      biologists to determine quickly which dataset or groups of datasets play a role
      in a biological function of interest. AVAILABILITY: A live online version of
      Sungear can be found at http://virtualplant-prod.bio.nyu.edu/cgi
      bin/sungear/index.cgi

PMID- 17018537
TI  - A Novel algorithm for identifying low-complexity regions in a protein sequence.
AB  - MOTIVATION: We consider the problem of identifying low-complexity regions (LCRs)
      in a protein sequence. LCRs are regions of biased composition, normally
      consisting of different kinds of repeats. RESULTS: We define new complexity
      measures to compute the complexity of a sequence based on a given scoring matrix,
      such as BLOSUM 62. Our complexity measures also consider the order of amino acids
      in the sequence and the sequence length. We develop a novel graph-based algorithm
      called GBA to identify LCRs in a protein sequence. In the graph constructed for
      the sequence, each vertex corresponds to a pair of similar amino acids. Each edge
      connects two pairs of amino acids that can be grouped together to form a longer
      repeat. GBA finds short subsequences as LCR candidates by traversing this graph.
      It then extends them to find longer subsequences that may contain full repeats
      with low complexities. Extended subsequences are then post-processed to refine
      repeats to LCRs. Our experiments on real data show that GBA has significantly
      higher recall compared to existing algorithms, including 0j.py, CARD, and SEG.
      AVAILABILITY: The program is available on request.

PMID- 17018538
TI  - The 'distal-dorsal difference': a thermographic parameter by which to
      differentiate between primary and secondary Raynaud's phenomenon.
AB  - OBJECTIVE: To test the hypothesis that in a patient with Raynaud's phenomenon
      (RP), a difference of >1 degrees C between the fingertips and the dorsum of the
      hand ['distal-dorsal difference' (DDD), fingers cooler] is specific for
      underlying structural vascular disease as occurs in systemic sclerosis (SSc), and
      to evaluate other thermographic parameters in the separation of secondary from
      primary RP. METHODS: A retrospective analysis of the case notes and thermography
      results of patients attending thermography, primarily over a 2-yr period.
      Multinomial logistic regression was used to ascertain whether thermography
      variables differed between groups with primary RP (56 patients), undifferentiated
      connective tissue disease (21 patients) and SSc (45 patients), with adjustment
      for age, sex and smoking. RESULTS: A DDD >1 degrees C in any finger at 30 degrees
      C had a positive predictive value of 70%, and a negative predictive value of 82%,
      in identifying the patient with RP secondary to SSc. From the results of the
      multinomial logistic regression, a score was derived incorporating age, number of
      fingers with DDD >1 degrees C at 30 degrees C and maximum rewarming gradient.
      This score (with a suitable cut-off) was 82% sensitive and 82% specific in
      identifying RP secondary to SSc, with a positive predictive value of 73% and a
      negative predictive value of 89%. CONCLUSION: Parameters derived from
      thermography (incorporating both a heat and cold challenge) aid in the prediction
      of SSc in patients with RP.

PMID- 17018539
TI  - Urokinase for restoration of patency of occluded permanent central venous access
      in haemodialysis patients--a new protocol.

PMID- 17018540
TI  - Significant negative association with age and both GFR and ERPF in male and
      female living kidney donors.

PMID- 17018541
TI  - Trisodium citrate 4%--an alternative to heparin capping of haemodialysis
      catheters.
AB  - BACKGROUND: Central venous catheters (CVCs) continue to be used at a high rate
      for dialysis access and are frequently complicated by thrombus-related
      malfunction. Prophylactic locking with an anticoagulant, such as heparin, has
      become standard practice despite its associated risks. Trisodium citrate
      (citrate) 4% is an alternative catheter locking anticoagulant. METHODS: The
      objective was to prospectively study the clinical effectiveness, safety and cost
      of citrate 4% vs heparin locking by comparing rates of CVC exchanges,
      thrombolytic use (TPA) and access-associated hospitalizations during two study
      periods: heparin period (HP) (1 June 2003-15 February 2004) and Citrate Period
      (CP) 15 March-15 November 2004. Incident catheters evaluated did not overlap the
      two periods. RESULTS: There were 176 CVC in 121 patients (HP) and 177 CVC in 129
      patients (CP). The event rates in incident CVC were: CVC exchange 2.98/1000 days
      (HP) vs 1.65/1000 days (CP) (P = 0.01); TPA use 5.49/1000 (HP) vs 3.3/1000 days
      (CP) (P = 0.002); hospitalizations 0.59/1000 days (HP) vs 0.28/1000 days (CP) (P
      = 0.49). There was a longer time from catheter insertion to requiring CVC
      exchange (P = 0.04) and TPA (P = 0.006) in the citrate compared with the heparin
      lock group. Citrate locking costs less than heparin locking but a formal economic
      analysis including indirect costs was not done. CONCLUSION: Citrate 4% has
      equivalent or better outcomes with regards to catheter exchange, TPA use and
      access-related hospitalizations compared with heparin locking. It is a safe and
      less expensive alternative. Randomized trials comparing these anticoagulants with
      a control group would definitively determine the optimal haemodialysis catheter
      locking solution.

PMID- 17018542
TI  - Eplerenone relieves spironolactone-induced painful gynaecomastia in a patient
      with primary aldosteronism.

PMID- 17018543
TI  - Experience of radiation passbooks in the UK NRPB dose record keeping service.
AB  - The National Radiological Protection Board (NRPB)--now part of the new UK Health
      Protection Agency (HPA)--has operated an automated Dose Record Keeping (DRK)
      Service for over 30 y, and currently maintains records for some 10,000 workers. A
      proportion of these are designated as Outside Workers, and are issued with
      Radiation Passbooks, under the Ionising Radiations Regulations 1999 (IRR99). The
      present study reports the operational experience of NRPB's DRK Service in issuing
      passbooks, providing advice to users and issuing tailored reports. Indication is
      given on some problems commonly encountered by employers and dosimetry services.

PMID- 17018544
TI  - Analysing an accident related to orphan sources including dose assessment.
AB  - This paper discusses an accident, which occurred in one of the radiation
      application centres in Iran, follow-up investigations as well as lessons learnt.
      In January 2004 the Regulatory Authority was informed through a university
      radiation protection officer of an accident regarding orphan sources.
      Investigations revealed that one Am-Be and three (137)Cs sources in the container
      were subject to extensive heat due to burning of the container and melting of the
      paraffin content of the container; consequently, sources were stuck to the side
      wall of the container, but they were still undamaged and no radioactive leaking
      had occurred. Further investigations showed that the container had been given to
      the above mentioned centre a long time before by a foreign well-logging company
      without notifying the Regulatory Authority. Follow-up measurements and
      assessments indicated that the collective effective dose due to the accident is
      unlikely to be more than 21 mSv; consequently, no severe deterministic effect to
      individuals was expected. The findings showed that the main reasons for the
      accident were as follows: (1) violation of obligation under radiation protection
      regulations by the owner of the sources; (2) leaving the sources in an improper
      storage condition; (3) unauthorised access to the radiation sources at the owner
      centre; and (4) lack of an integrated national registration system in the
      Regulatory Authority.

PMID- 17018545
TI  - Application of voxel phantoms in whole-body counting for the validation of
      calibration phantoms and the assessment of uncertainties.
AB  - This article is dedicated to the application of voxel phantoms in whole-body
      counting calibration. The first study was performed to validate this approach
      using IGOR, a physical phantom dedicated to fission and activation product (FAP)
      measurement, and a graphical user interface, developed at the IRSN internal dose
      assessment laboratory, called OEDIPE (French acronym for the tool for
      personalised internal dose assessment) associated with the Monte Carlo code MCNP.
      The method was validated by comparing the results of real measurements and
      simulations using voxel phantoms obtained from CT scan images of IGOR. To take
      this application further, two studies were carried out and are presented in this
      article. First, a comparison was made between the IGOR voxel based phantom
      (IGOVOX) and a voxel human body (Zubal Phantom) to confirm whether IGOR could be
      considered as a realistic representation of a human. Second, the errors made when
      considering sources homogeneously distributed in the body were assessed against
      real contamination by taking into account the biokinetic behaviour of the
      radioactive material for two modes of exposure: the ingestion of 137Cs in soluble
      form and the inhalation of insoluble 60Co several days after acute incorporation.

PMID- 17018546
TI  - Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without
      compromising tumor suppression.

PMID- 17018547
TI  - Giant right atrial aneurysm in a symptomatic adult-a rare congenital
      malformation.

PMID- 17018548
TI  - Public smoking ban: Europe on the move.

PMID- 17018549
TI  - Therapeutic approaches to Alzheimer's disease.
AB  - Alzheimer's disease is an age-related progressive neurodegenerative disorder with
      an enormous unmet medical need. It is the most common form of dementia affecting
      approximately 5% of adults over 65 years. In view of our ageing society the
      number of patients, as well as the economical and social impact, is expected to
      grow dramatically in the future. Currently available medications appear to be
      able to produce moderate symptomatic benefits but not to stop disease
      progression. The search for novel therapeutic approaches targeting the presumed
      underlying pathogenic mechanisms has been a major focus of research and it is
      expected that novel medications with disease-modifying properties will emerge
      from these efforts in the future. In this review, currently available drugs as
      well as novel therapeutic strategies, in particular those targeting amyloid and
      tau pathologies, are discussed.

PMID- 17018550
TI  - Exaggerated interlimb neural coupling following stroke.
AB  - The patterns of interlimb coupling were examined in 10 stroke survivors with
      chronic hand impairment. In particular, the potential roles of postural state and
      motor tasks in promoting the flexed posture of the upper extremity were assessed.
      Through the use of electromyography analysis, joint angle measurements and a
      novel biomechanical apparatus to perturb the digits of the hand into extension,
      measurements of muscle activity and joint position were compared during multiple
      postural states, locomotion and voluntary muscle activity. The results
      demonstrated a significant increase in flexion of the digits (P < 0.001) and
      elbow (P < 0.005), during walking as compared with standing, sitting or laying
      supine. These results were indicative of an overall excessive activation coupling
      between the upper and lower extremities after stroke. Indeed both voluntary
      finger flexion and voluntary leg extension produced significant activity in the
      other impaired extremity, leg and arm, respectively, in the stroke as compared
      with the control subjects. Thus, rectus femoris in the impaired leg was active
      during finger flexion of the impaired hand in the stroke survivors and all four
      tested muscles in the impaired arm were active during extension of the legs (P <
      0.05). These findings suggest an interlimb coupling related to active motor
      tasks, contributing to an upper extremity flexion bias following stroke.

PMID- 17018551
TI  - Neuronal differentiation of transplanted embryonic stem cell-derived precursors
      in stroke lesions of adult rats.
AB  - Stroke represents one of the leading causes of death and disability in Western
      countries, but despite intense research, only few options exist for the treatment
      of stroke-related infarction of brain tissue. In experimental stroke, cell
      therapy can partly reverse some behavioural deficits. However, the underlying
      mechanisms have remained unknown as most studies revealed only little, if any,
      evidence for neuronal replacement and the observed behavioural improvements
      appeared to be related rather to a graft-derived induction of a positive response
      in the remaining host tissue than to cell replacement by the graft itself. The
      present study was performed to test a murine embryonic stem cell (ESC)-based
      approach in rats subjected to endothelin-induced middle cerebral artery
      occlusion. Efficacy of cell therapy regarding graft survival, neuronal yield and
      diversity, and electrophysiological features of the grafted cells were tested
      after transplanting ESC-derived neural precursors into the infarct core and
      periphery of adult rats. Here, we show that grafted cells can survive, albeit not
      entirely, most probably as a consequence of an ongoing immune response, within
      the infarct core for up to 12 weeks after transplantation and that they
      differentiate with high yield into immunohistochemically mature glial cells and
      neurons of diverse neurotransmitter-subtypes. Most importantly, transplanted
      cells demonstrate characteristics of electrophysiologically functional neurons
      with voltage-gated sodium currents that enable these cells to fire action
      potentials. Additionally, during the first 7 weeks after transplantation we
      observed spontaneous excitatory post-synaptic currents in graft-derived cells
      indicating synaptic input. Thus, our observations show that ESC-based
      regenerative approaches may be successful in an acutely necrotic cellular
      environment.

PMID- 17018552
TI  - 3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and
      Alzheimer's disease.
AB  - Alzheimer's disease is the most common neurodegenerative disorder in the elderly.
      Amnestic mild cognitive impairment (MCI) is a relatively newly defined clinical
      entity that requires memory decline while activities of daily living remain
      intact. Most amnestic MCI patients develop Alzheimer's disease. Using an
      innovative surface-based hippocampal analytic technique we analysed the
      structural magnetic resonance hippocampal data of 31 amnestic MCI and 34
      Alzheimer's disease subjects. We tested the hypothesis that Alzheimer's disease
      subjects have greater atrophy of the CA1, CA2 and CA3 hippocampal subfields
      relative to amnestic MCI subjects. 3D hippocampal maps localized the main group
      differences to the CA1 region bilaterally and the CA2 and CA3 region on the left
      [corrected] (right [corrected] P = 0.0024, left [corrected] P = 0.0002, both
      corrected for multiple comparisons). Age, race, gender, education and Mini-Mental
      State Examination were significant predictors of hippocampal volume. Hippocampal
      volume was a significant predictor of clinical diagnosis. Our study suggests that
      as Alzheimer's disease progresses, subregional hippocampal atrophy spreads in a
      pattern that follows the known trajectory of neurofibrillary tangle
      dissemination. Novel hippocampal analytic techniques that can track the spread of
      hippocampal pathology in 3D with such precision are a promising research tool.

PMID- 17018553
TI  - Family socialization of adolescent's self-reported cigarette use: the role of
      parents' history of regular smoking and parenting style.
AB  - OBJECTIVE: To examine the main and interactive effects of parental history of
      regular cigarette smoking and parenting style on adolescent self-reported
      cigarette use. METHODS: Predictors of adolescent self-reported cigarette use,
      including parents' history of regular cigarette smoking and two dimensions of
      parenting behavior, were analyzed in a sample of 934 predominately Caucasian
      (96.3%) parent-adolescent dyads. Families were drawn from the control group of a
      randomized control trial aimed at preventing adolescent substance use. RESULTS:
      In addition to the main effects of parents' history of regular smoking and
      parental warmth, logistic regression analysis revealed that the interaction of
      these two variables was associated with adolescent self-reported cigarette use.
      Parental warmth was associated with a decreased likelihood of the adolescent ever
      having smoked a cigarette; however, this was true only if neither parent had a
      history of regular cigarette smoking. CONCLUSIONS: Findings suggest that
      adolescent smoking prevention programs may be more efficacious if they address
      both parental history of regular smoking and parenting behavior.

PMID- 17018554
TI  - Longitudinal relationships between early adolescent family functioning and youth
      adjustment: an examination of the moderating role of very low birth weight.
AB  - OBJECTIVE: To examine longitudinal relations between early adolescent family
      conflict and late adolescent psychosocial adjustment, and the moderating role of
      low birth weight. METHODS: Three groups of adolescents (48 with birth weight <750
      g, 46 with birth weight 750-1499 g, and 51 term-born controls) and their parents
      completed ratings of family conflict at age 11 (Time 1). Parent, teacher, and
      youth reports of psychosocial functioning were obtained at ages 11 and 17 (Time
      2). RESULTS: Birth weight moderated the relationship between Time 1 adolescent
      perceived conflict and change in adolescent behavioral functioning. For
      adolescents with histories of <750 g birth weight, adolescent-perceived conflict
      predicted less adaptive changes in teacher-reported total behavior problems and
      externalizing problems. CONCLUSIONS: Small disruptions to the parent-child
      relationship have negative implications for the later well-being of adolescents
      with extreme levels of low birth weight. Clinical attention to resolving early
      adolescent conflict may promote adaptive adjustment.

PMID- 17018555
TI  - Impact of severity of a child's chronic condition on the functioning of two
      parent families.
AB  - OBJECTIVE: To examine the impact of the severity of a child's chronic condition
      on family functioning from the perspectives of mothers and fathers and to compare
      their reports with the functioning of families with healthy children. METHODS:
      Mothers and fathers in two-parent families of 160 infants and 102 pre-adolescents
      with a wide range of chronic health conditions (noncategorical approach)
      completed standard self-report inventories. RESULTS: The families of children
      with chronic conditions functioned as well or better compared with normative data
      for families with healthy children. The only significant differences between
      mothers' and fathers' reports of family functioning were a greater negative
      impact on role performance reported by mothers of infants and pre-adolescents and
      a great negative impact on affective expression reported by fathers of pre
      adolescents. CONCLUSIONS: Overall, very little of the variance in family
      functioning was explained by severity of the child's chronic condition in this
      sample of middle-class, two-parent families.

PMID- 17018556
TI  - Three distinct-type glutathione S-transferases from Escherichia coli important
      for defense against oxidative stress.
AB  - Previously, we characterized glutathione S-transferase (GST) B1-1 from
      Escherichia coli enzymologically and structurally. Besides GST B1-1, E. coli has
      seven genes that encode GST-like proteins, for which, except SspA, neither
      biological roles nor biochemical properties are known. Here we show that the GST
      like YfcF and YfcG proteins have low but significant GSH-conjugating activity
      toward 1-chloro-2,4-dinitorobenzene and GSH-dependent peroxidase activity toward
      cumene hydroperoxide. Analysis involving site-directed mutagenesis suggested that
      Ser16 and Asn11 were important for the activities of YfcF and YfcG, respectively.
      On the contrary, no residue around the catalytic site of GST B1-1 has been
      demonstrated to be essential for catalytic activity. Deletions of the gst, yfcF,
      and yfcG genes each decreased the resistibility of the bacteria to hydrogen
      peroxide, which was recovered by transformation with the expression plasmid for
      the deleted enzyme. The inactive YfcF(S16G) and YfcG(N11A) mutants, however,
      could not rescue the knockout bacteria. Thus, E. coli has at least three GSTs of
      distinct classes, all of which are important for defense against oxidative stress
      in spite of the structural diversity. This seems consistent with the hypothesis
      that GSTs constitute a protein superfamily that has evolved from a thioredoxin
      like ancestor in response to the development of oxidative stress.

PMID- 17018557
TI  - Bacterial lipopolysaccharides induce defense responses associated with programmed
      cell death in rice cells.
AB  - PAMP (pathogen-associated molecular pattern) recognition plays an important role
      during the innate immune response in both plants and animals. Lipopolysaccharides
      (LPS) derived from Gram-negative bacteria are representative of typical PAMP
      molecules and have been reported to induce defense-related responses, including
      the suppression of the hypersensitive response, the expression of defense genes
      and systemic resistance in plants. However, the details regarding the precise
      molecular mechanisms underlying these cellular responses, such as the molecular
      machinery involved in the perception and transduction of LPS molecules, remain
      largely unknown. Furthermore, the biological activities of LPS on plants have so
      far been reported only in dicots and no information is thus available regarding
      their functions in monocots. In our current study, we report that LPS
      preparations for various becteria, including plant pathogens and non-pathogens,
      can induce defense responses in rice cells, including reactive oxygen generation
      and defense gene expression. In addition, global analysis of gene expression
      induced by two PAMPs, LPS and chitin oligosaccharide, also reveals a close
      correlation between the gene responses induced by these factors. This indicates
      that there is a convergence of signaling cascades downstream of their
      corresponding receptors. Furthermore, we show that the defense responses induced
      by LPS in the rice cells are associated with programmed cell death (PCD), which
      is a finding that has not been previously reported for the functional role of
      these molecules in plant cells. Interestingly, PCD induction by the LPS was not
      detected in cultured Arabidopsis thaliana cells.

PMID- 17018558
TI  - Genetic transformation of Populus trichocarpa genotype Nisqually-1: a functional
      genomic tool for woody plants.
AB  - We report here the Agrobacterium-mediated genetic transformation of Nisqually-1,
      a Populus trichocarpa genotype whose genome was recently sequenced. Several
      systems were established. Internodal stem segments from vigorously growing
      greenhouse plants are the explants most amenable to transformation. For the most
      efficient system, approximately 40% of the stem segments infected with pBI121
      containing Agrobacterium tumefaciens C58 produced transgenic calli, as confirmed
      by beta-glucuronidase (GUS) staining. The regeneration efficiency of independent
      transgenic plants was approximately 13%, as revealed by genomic Southern
      analysis. Some transgenic plants were produced in as little as 5 months after co
      cultivation. This system may help to facilitate studies of gene functions in tree
      growth and development at a genome level.

PMID- 17018559
TI  - Obstructive sleep apnoea: an underestimated cause of peripheral neuropathy.

PMID- 17018560
TI  - Limbic encephalitis: extension of the diagnostic armamentarium.

PMID- 17018561
TI  - Primary glomerulonephritis with isolated C3 deposits: a new entity which shares
      common genetic risk factors with haemolytic uraemic syndrome.
AB  - INTRODUCTION: Abnormal control of the complement alternative pathway (CAP)
      (factor H, factor I and membrane cofactor protein (MCP) deficiencies) is a well
      established risk factor for the occurrence of haemolytic uraemic syndrome (HUS).
      In some instances, HUS may be associated with an unusual glomerulonephritis with
      isolated C3 deposits (glomerulonephritis C3). We determined whether HUS and
      glomerulonephritis C3 share common genetic susceptibility factors. METHODS: We
      identified 19 patients with glomerulonephritis C3. We measured levels of
      circulating complement components, performed assays for the detection of C3
      nephritic factor (C3NeF) and screened factor H, factor I and MCP coding genes for
      the presence of mutations. RESULTS: Patients were divided in two groups based on
      renal pathology findings: group I (n = 13) had typical features of type I
      membranoproliferative glomerulonephritis (glomerulonephritis C3 with
      membranoproliferative glomerulonephritis (MPGN)) and group II (n = 6) was
      characterised by mesangial and epimembranous C3 deposits in the absence of
      mesangial proliferation (glomerulonephritis C3 without MPGN). Mutations in
      complement regulatory genes were detected in 4/6 patients with glomerulonephritis
      C3 without MPGN (heterozygous mutations in factor H gene (two patients) with low
      factor H antigenic level in one case, heterozygous mutations in factor I gene
      (two patients)) and in only 2/13 patients with glomerulonephritis C3 with MPGN
      (heterozygous mutations in factor H gene (one patient) and double heterozygous
      mutation in CD 46 gene (one patient)). In contrast, C3NeF was present in 5/13
      patients with glomerulonephritis C3 with MPGN and in 2/6 patients with
      glomerulonephritis C3 without MPGN, one of whom had a factor H mutation.
      CONCLUSION: HUS and glomerulonephritis C3 without MPGN share common genetic risk
      factors. Constitutional or acquired dysregulation of the CAP is probably
      associated with a wide spectrum of diseases, ranging from HUS to
      glomerulonephritis C3 with MPGN.

PMID- 17018562
TI  - Replication of twelve association studies for Huntington's disease residual age
      of onset in large Venezuelan kindreds.
AB  - BACKGROUND: The major determinant of age of onset in Huntington's disease is the
      length of the causative triplet CAG repeat. Significant variance remains,
      however, in residual age of onset even after repeat length is factored out. Many
      genetic polymorphisms have previously shown evidence of association with age of
      onset of Huntington's disease in several different populations. OBJECTIVE: To
      replicate these genetic association tests in 443 affected people from a large set
      of kindreds from Venezuela. METHODS: Previously tested polymorphisms were
      analysed in the HD gene itself (HD), the GluR6 kainate glutamate receptor
      (GRIK2), apolipoprotein E (APOE), the transcriptional coactivator CA150 (TCERG1),
      the ubiquitin carboxy-terminal hydrolase L1 (UCHL1), p53 (TP53), caspase
      activated DNase (DFFB), and the NR2A and NR2B glutamate receptor subunits
      (GRIN2A, GRIN2B). RESULTS: The GRIN2A single-nucleotide polymorphism explains a
      small but considerable amount of additional variance in residual age of onset in
      our sample. The TCERG1 microsatellite shows a trend towards association but does
      not reach statistical significance, perhaps because of the uninformative nature
      of the polymorphism caused by extreme allele frequencies. We did not replicate
      the genetic association of any of the other genes. CONCLUSIONS: GRIN2A and TCERG1
      may show true association with residual age of onset for Huntington's disease.
      The most surprising negative result is for the GRIK2 (TAA)(n) polymorphism, which
      has previously shown association with age of onset in four independent
      populations with Huntington's disease. The lack of association in the Venezuelan
      kindreds may be due to the extremely low frequency of the key (TAA)(16) allele in
      this population.

PMID- 17018563
TI  - High-level resistance to moxifloxacin and gatifloxacin associated with a novel
      mutation in gyrB in toxin-A-negative, toxin-B-positive Clostridium difficile.
AB  - OBJECTIVES: To determine the mechanism of high-level resistance to
      fluoroquinolone antimicrobials in toxin-A-negative, toxin-B-positive (A- B+)
      Clostridium difficile isolates. METHODS: Following culture 16-23S PCR ribotyping
      was used to determine genomic relationships between A- B+ C. difficile isolates.
      Antimicrobial susceptibilities were determined using Etests in the presence and
      absence of the efflux pump inhibitors reserpine (20 microg/mL), L-phenylalanine-L
      arginine-beta-naphthylamide (PAbetaN; 20 microg/mL) and verapamil (100
      microg/mL). Genomic regions including the quinolone-resistance-determining-region
      (QRDR) of gyrA and gyrB were amplified and characterized. RESULTS: PCR ribotyping
      profiles identified one major cluster of A- B+ C. difficile, universally
      resistant to the fluoroquinolones tested (ofloxacin, ciprofloxacin, levofloxacin,
      moxifloxacin and gatifloxacin; MICs > 32 mg/L). All isolates with high-level
      resistance had a transversion mutation (A-->T) resulting in the amino acid
      substitution Asp-426-->Val in gyrB. Non-clonal isolates were susceptible to
      moxifloxacin and gatifloxacin (MICs 0.3 and 0.4 mg/L, respectively) with reduced
      susceptibility to levofloxacin (MIC 3 mg/L) consistent with the wild-type
      genotype. The MICs for resistant isolates were not significantly affected by the
      addition of any of the efflux pump inhibitors. No amino acid substitutions were
      identified in the QRDR of gyrA. CONCLUSIONS: High-level resistance to
      fluoroquinolones in A- B+ C. difficile is associated with a novel transversion
      mutation in gyrB. The emergence of universal resistance in different C. difficile
      strain types may be a factor promoting outbreaks in hospitals.

PMID- 17018564
TI  - Time course of action of sugammadex (Org 25969) on rocuronium-induced block in
      the Rhesus monkey, using a simple model of equilibration of complex formation.
AB  - BACKGROUND: Reversal of neuromuscular block can be accomplished by chemical
      encapsulation of rocuronium by sugammadex (Org 25969), a synthetic gamma
      cyclodextrin derivative. The present study determined the time course of the
      reversal action of sugammadex on rocuronium-induced block in the anaesthetized
      Rhesus monkey using train-of-four stimulation. METHODS: A bolus injection of
      rocuronium 100 microg kg(-1) (about 1xED(90)) was given to determine the degree
      of neuromuscular block reached by this dose. After complete spontaneous recovery,
      a rapid bolus injection of sugammadex, 1 mg kg(-1), was given and at different
      time intervals (15, 30 or 60 min, in three different experiments) the effect of
      another rocuronium bolus injection of 100 microg kg(-1) was determined. RESULTS:
      Injection of the first dose of rocuronium resulted in a mean neuromuscular block
      (depression of first twitch) of 93 (SEM=1.6)%. Fifteen minutes after injection of
      sugammadex the same rocuronium dose resulted in 17% (SEM=5.6) block. After 30 and
      60 min these maximum blocks amounted to 49% (SEM=7.6) and 79% (SEM=4.2),
      respectively. The estimated half-life of sugammadex in Rhesus monkey is 30
      (SEM=4.9) min. CONCLUSIONS: The half-life of sugammadex (Org 25969), a new fast
      and efficient reversal agent for rocuronium-induced block, is relatively short in
      the Rhesus monkey, implying the possibility to perform neuromuscular block by
      rocuronium shortly after reversal of a prior block. In translation to the human
      situation differences in rocuronium sensitivity and kinetics should be taken into
      account.

PMID- 17018565
TI  - Tracking health care costs: continued stability but at high rates in 2005.
AB  - Health care spending per privately insured person increased 7.4 percent in 2005,
      marking the third year that the cost trend hovered between 7 and 8 percent
      following double-digit trends in 2001 and 2002. Data for the first quarter of
      2006 suggest continued stability. The trend for 2005 reflected increased growth
      in spending for hospital and physician care, offsetting a sharp drop in spending
      growth for prescription drugs. Hospital utilization trends accelerated, while
      price trends decelerated in 2005. In contrast to stable spending trends in 2005,
      premium trends continued to decline in 2006, likely reflecting the lagged effects
      of earlier years' slowing in cost trends and perhaps signaling a turn in the
      insurance underwriting cycle.

PMID- 17018566
TI  - The origin, initiation and development of axillary shoot meristems in Lotus
      japonicus.
AB  - BACKGROUND AND AIMS: Lotus japonicus 'Gifu' develops multiple axillary shoots in
      the cotyledonary node region throughout the growth of the plant. The origin,
      initiation and development of these axillary meristems were investigated.
      METHODS: Morphological, histological and mRNA in situ analyses were done to
      characterize the ontogeny of cotyledonary axillary shoot meristems in Lotus.
      Morphological characterization of a putative Lotus shoot branching mutant (super
      accessory branches) sac, is presented. KEY RESULTS: By using expression of an L.
      japonicus STM-like gene as a marker for meristematic tissues, it was demonstrated
      that groups of cells maintained in the meristematic state at the cotyledonary
      axil region coincide with the sites where additional axillary meristems
      (accessory meristems) form. A Lotus shoot branching mutant, sac, is a putative
      Lotus branching mutant characterized by increased proliferation of accessory
      shoots in all leaf axils including the cotyledons. CONCLUSION: In Lotus, axillary
      shoot meristems continually develop at the cotyledonary node region throughout
      the growth of the plant. These cotyledonary primary and accessory axillaries
      arise from the position of a meristematic zone of tissue at the cotyledonary node
      axil region.

PMID- 17018567
TI  - Adventitious root production and plastic resource allocation to biomass determine
      burial tolerance in woody plants from central Canadian coastal dunes.
AB  - BACKGROUND AND AIMS: Burial is a recurrent stress imposed upon plants of coastal
      dunes. Woody plants are buried on open coastal dunes and in forested areas behind
      active blowouts; however, little is known about the burial responses and adaptive
      traits of these species. The objectives of this study were: (a) to determine the
      growth and morphological responses to burial in sand of seven woody plant species
      native to central Canadian coastal dunes; and (b) to identify traits that
      determine burial tolerance in these species. METHODS: Field experiments were
      conducted to determine the responses of each species to burial. Saplings were
      exposed to burial treatments of 0, 10, 25, 50 and 75 % of their height. Burial
      responses were evaluated based on regressions of total biomass, height,
      adventitious root production and percentage allocation to shoot, root and
      adventitious root biomass on percentage burial. KEY RESULTS: Pinus strobus and
      Picea glauca lacked burial tolerance. In response to the burial gradient, these
      species showed a strong linear decline in total biomass, minimal adventitious
      root production that peaked at moderate levels (25-50 % burial) and no change in
      allocation to shoots vs. roots. The tolerant species Juniperus virginiana, Thuja
      occidentalis and Picea mariana showed a quadratic response to burial, with little
      change in biomass up to 50 % burial, but a large decline at 75 %. These species
      produced abundant adventitious roots up to 50 % burial, but did not alter
      allocation patterns over the range of burial levels. Populus balsamifera and
      Salix cordata were stimulated by burial. These species showed linear increases in
      biomass with increasing burial, produced copious adventitious roots across the
      gradient and showed a clear shift in allocation to vertical shoot growth and
      adventitious root production at the expense of the original roots under high
      burial conditions. CONCLUSIONS: Adventitious root production and plastic resource
      allocation to biomass are adaptive traits of coastal dune woody plants in central
      Canada, and provide a basis for assessing burial tolerance in woody plants on
      coastal dunes throughout the world.

PMID- 17018568
TI  - The role of thermogenesis in the pollination biology of the Amazon waterlily
      Victoria amazonica.
AB  - BACKGROUND AND AIMS: Several families of tropical plants have thermogenic flowers
      that show a 2-d protogynous sequence. Most are pollinated by large beetles that
      remain for the entire period in the flowers, where they compete for mates and
      feed. Active beetles require high body temperatures that they can achieve
      endogenously at great energy expense or attain passively and cheaply in a warm
      environment. Floral heating is therefore hypothesized to be a direct energy
      reward to endothermic beetles, in addition to its accepted role in enhancing
      scent production. METHODS: This study measures the pattern of floral heat
      production (as temperature in 20 flowers and respiration rates in five flowers)
      in Victoria amazonica at field sites in Guyana and correlates floral temperatures
      with body temperatures necessary for activity in visiting Cyclocephala hardyi
      beetles. KEY RESULTS: Thermogenesis occurred in a bimodal pattern, with peaks
      associated with the arrival and departure of beetles near sunset. Peak CO(2)
      production rates averaged 2.9 micromol s(-1), equivalent to a heat production of
      1.4 W. Heat was generated mainly in the floral chamber on the first evening and
      by the stamen complex on the second. Mean chamber temperature remained between
      29.3 and 34.7 degrees C during the first night, when ambient temperature was 23.5
      25.2 degrees C. Beetles actively competed for mates and consumed stylar processes
      in the floral chamber, where their mean thoracic temperature was 33.2 degrees C.
      At the lower ambient temperatures outside of the flower, beetles capable of
      sustained flight had a similar mean temperature of 32.0 degrees C. CONCLUSIONS:
      Floral heating is not only associated with attraction, but continues throughout
      the night when beetles are active inside the flower and increases again when they
      leave. Floral chamber temperatures similar to activity temperatures of actively
      endothermic beetles imply that thermogenesis is an energy reward.

PMID- 17018569
TI  - Evolutionary and morphometric implications of morphological variation among
      flowers within an inflorescence: a case-study using European orchids.
AB  - BACKGROUND AND AIMS: This study explores the previously largely ignored
      morphological variation that occurs among flowers within a single inflorescence.
      METHODS: Variation in four metric parameters (labellum length and width, spur
      length and width) that together strongly influence pollination frequency is
      documented within the simple racemose inflorescences of eight individuals that
      represent a primary hybrid and six species of European orchids. KEY RESULTS:
      Regression of each parameter against the location of each flower on the
      inflorescence, and calculation of correlation coefficients for each pair of
      parameters within each inflorescence, demonstrate significant decoupling of
      labellum and spur development, despite the fact that they are different portions
      of the same floral organ. Spur length and diameter are constant across
      inflorescences of Dactylorhiza other than the vestigial-spurred D. viridis,
      whereas in other genera spur length declines in parallel with labellum
      dimensions. These differences are likely to reflect selection pressures or
      developmental constraints. Strong negative deviations from the regression line
      for one or more parameters are evident in occasional flowers, occurring most
      frequently in the lowermost and uppermost one or two flowers, and so reflecting
      transitions in meristematic behaviour. Thus, population-level morphometric
      studies are best conducted on flowers taken from approximately the mid-point of
      the inflorescence. Moreover, in the two relatively large inflorescences where
      lower flowers were removed for measurement before the upper flowers had opened,
      labellum size increased significantly in the flowers immediately above the
      excisions, suggesting that excision liberated resources that were diverted into
      the opening buds. Repeat measurement of all flowers from one selected
      inflorescence demonstrated typical measurement errors of only +/- 30-80 micro m,
      irrespective of the size of the structure studied. If flowers are not mounted and
      measured immediately following excision, modest negative deviations of 30-50
      micro m result from post-mounting shrinkage; this occurs less rapidly in the spur
      than in the thinner labellum, which should therefore be measured first. Variation
      in all four parameters among all the flowers of a single inflorescence is between
      42 % and 107 % of that observed between a similar number of flowers sampled from
      a consistent location on different (but conspecific and coexisting)
      inflorescences. CONCLUSIONS: This result demonstrates the strong influence of
      epigenesis on flower morphology and further emphasizes the importance of (a)
      sampling from a consistent location within the inflorescences under comparison,
      (b) interpreting morphometric ordinations hierarchically, building from
      individuals to infraspecific taxa and species via populations, and (c)
      considering in any microevolutionary study the potentially profound effects of
      the cline in flower size within each inflorescence.

PMID- 17018570
TI  - Multiphase modelling of cell behaviour on artificial scaffolds: effects of
      nutrient depletion and spatially nonuniform porosity.
AB  - This paper contains analysis of a recently formulated multiphase model for the
      growth of biological tissue that comprises motile cells and water inside a rigid
      scaffold material. The model is extended here to include a term describing cell
      proliferation which is mediated by the supply of a diffusible nutrient and to
      include the case where the scaffold porosity varies in space. Numerical solutions
      of the model equations are presented for different values of the parameters.
      Comparison is drawn between the different types of growth that arise when using
      static or dynamic methods for seeding the scaffold with cells. Analytical
      solutions are presented for the limiting cases in which the coefficient of drag
      between the cells and the scaffold is very large or zero. In the limit of large
      time, solutions reveal preferential tissue growth in the vicinity of the scaffold
      edge due to depletion of nutrient by the cells, consistent with experimental
      results. However, it is shown that reducing the coefficient of drag between the
      scaffold and the cells overcomes the effects of nutrient depletion by increasing
      cell mobility, thereby leading to improved uniformity of the cell distribution
      within the scaffold.

PMID- 17018571
TI  - Fibrin gel formation in a shear flow.
AB  - Blood clots are made up of platelets and fibrin gel, and the relative amount of
      fibrin is strongly influenced by the shear rate. In order to explore this
      phenomenon, this paper presents a model of fibrin gel formation over the surface
      of an injured blood vessel in a shear flow. A condition for gelation including
      source and sink terms of polymer is derived. A simplified model of coagulation,
      involving activation and inhibition of the enzyme thrombin and thrombin-mediated
      production of fibrin monomer, is combined with the model of gelation to explore
      how the shear rate and other parameters control the formation of fibrin gel. The
      results show that the thrombin inhibition rate, the gel permeability and the
      shear rate are key parameters in regulating the height of the fibrin gel.

PMID- 17018572
TI  - RNA editing in Drosophila melanogaster: New targets and functional consequences.
AB  - Adenosine deaminases that act on RNA [adenosine deaminase, RNA specific (ADAR)]
      catalyze the site-specific conversion of adenosine to inosine in primary mRNA
      transcripts. These re-coding events affect coding potential, splice sites, and
      stability of mature mRNAs. ADAR is an essential gene, and studies in mouse,
      Caenorhabditis elegans, and Drosophila suggest that its primary function is to
      modify adult behavior by altering signaling components in the nervous system. By
      comparing the sequence of isogenic cDNAs to genomic DNA, we have identified and
      experimentally verified 27 new targets of Drosophila ADAR. Our analyses led us to
      identify new classes of genes whose transcripts are targets of ADAR, including
      components of the actin cytoskeleton and genes involved in ion homeostasis and
      signal transduction. Our results indicate that editing in Drosophila increases
      the diversity of the proteome, and does so in a manner that has direct functional
      consequences on protein function.

PMID- 17018573
TI  - Selection and characterization of RNA aptamers to the RNA-dependent RNA
      polymerase from foot-and-mouth disease virus.
AB  - Foot-and-mouth disease virus causes a highly contagious disease of agricultural
      livestock and is of enormous economic importance. Replication of the RNA genome
      of the virus, via negative strand intermediates, involves an RNA-dependent RNA
      polymerase (3Dpol). RNA aptamers specific to this enzyme have been selected and
      characterized. Some of these molecules inhibit enzymatic activity in vitro, with
      IC50 values of <20 nM and Ki values of 18-75 nM. Two of these show similarity,
      both with each other and with regions of the viral genome. Furthermore, truncated
      versions of one of the aptamers have been used to define the parts of the
      molecule responsible for its inhibitory activity.

PMID- 17018575
TI  - Radiofrequency energy delivery for pulmonary vein isolation: is less more?

PMID- 17018574
TI  - Slx9p facilitates efficient ITS1 processing of pre-rRNA in Saccharomyces
      cerevisiae.
AB  - Slx9p (Ygr081cp) is a nonessential yeast protein previously linked genetically
      with the DNA helicase Sgs1p. Here we report that Slx9p is involved in ribosome
      biogenesis in the yeast Saccharomyces cerevisiae. Deletion of SLX9 results in a
      mild growth defect and a reduction in the level of 18S rRNA. Co
      immunoprecipitation experiments showed that Slx9p is associated with 35S, 23S,
      and 20S pre-rRNA, as well as U3 snoRNA and, thus, is a bona fide component of pre
      ribosomes. The most striking effects on pre-rRNA processing resulting from
      deletion of SLX9 is the accumulation of the mutually exclusive 21S and 27SA2 pre
      rRNA. Furthermore, deletion of SLX9 is synthetically lethal with mutations in
      Rrp5p that block cleavage at either site A2 or A3. We conclude that Slx9p has a
      unique role in the processing events responsible for separating the 66S and 43S
      pre-ribosomal particles. Interestingly, homologs of Slx9p were found only in
      other yeast species, indicating that the protein has been considerably less well
      conserved during evolution than the majority of trans-acting processing factors.

PMID- 17018576
TI  - Assessment of long-term quality of life using the FACT-BL questionnaire in
      patients with an ileal conduit, continent reservoir, or orthotopic neobladder.
AB  - OBJECTIVE: To assess and compare quality of life (QOL) of patients followed for a
      long time who underwent an ileal conduit (IC), continent reservoir (CR) or ileal
      neobladder (NB) using FACT-BL, a bladder-cancer-specific questionnaire. METHODS:
      One hundred and forty-seven patients underwent radical cystectomy and urinary
      diversion for bladder cancer from 1987 to 2002 at our institution. Of them, 79
      (54%) patients were asked to participate in this study. Forty-nine patients (20
      IC, 14 CR and 15 NB) returned the answered questionnaire for a survey response
      rate of 62%. Mean follow-up was 83.0 months. RESULTS: Four categories (physical,
      social/familial, emotional and functional well-being) in FACT-G were equally
      favorable in these groups. Patients with IC had less trouble controlling urine
      but had a worse image on altered body appearance compared with NB patients.
      Interest in sex was extremely low in all patients and capability of maintaining
      an erection was also low in 39 male patients. The mean total value of FACT-BL in
      IC, CR and NB patients was 106.3+/-16.4, 104.0+/-14.2, and 110.9+/-18.0,
      respectively, showing no significant difference. Ten (77%) of 13 IC, seven (78%)
      of nine CR and six (86%) of seven NB patients answered that they would choose the
      same type of diversion if they had the choice again. CONCLUSIONS: The type of
      urinary diversion does not appear to be associated with a different QOL by
      general cancer-related assessment. Urinary function and body image are affected
      and related to the method used to reconstruct the urinary system.

PMID- 17018577
TI  - Independent mechanistic inhibition of cdc25 phosphatases by a natural product
      caulibugulone.
AB  - Caulibugulones are novel but poorly characterized cytotoxic isoquinoline quinones
      and iminoquinones identified in extracts from the marine bryozoan Caulibugula
      intermis. We now report that the caulibugulones are selective in vitro inhibitors
      of the Cdc25 family of cell cycle-controlling protein phosphatases compared with
      either human vaccinia H1-related phosphatase (VHR) or tyrosine phosphatase 1B
      (PTP1B). The in vitro inhibition of Cdc25B by caulibugulone A was irreversible
      and attenuated by reducing agents or catalase, consistent with direct oxidation
      of the enzyme by reactive oxygen species. Mechanistically, caulibugulone A
      directly inhibited cellular Cdc25B activity, generated intracellular reactive
      oxygen species and arrested cells in both G1 and G2/M phases of the cell cycle.
      Caulibugulone A also caused the selective degradation of Cdc25A protein by a
      process that was independent of reactive oxygen species production, proteasome
      activity, and the Chk1 signaling pathway. Instead, caulibugulone A stimulated the
      phosphorylation and subsequent activation of p38 stress kinase, leading to Cdc25A
      degradation. Thus, caulibugulone inhibition of cellular Cdc25A and B phosphatases
      occurred through at least two different mechanisms, leading to pronounced cell
      cycle arrest.

PMID- 17018578
TI  - Motexafin gadolinium-induced cell death correlates with heme oxygenase-1
      expression and inhibition of P450 reductase-dependent activities.
AB  - Heme oxygenase-1 (HO1), which oxidizes heme to biliverdin, CO, and free iron,
      conveys protection against oxidative stress and is antiapoptotic. Under stress
      conditions, some porphyrin derivatives can inhibit HO1 and trigger cell death.
      Motexafin gadolinium (MGd) is an expanded porphyrin that selectively targets
      cancer cells through a process of futile redox cycling that decreases
      intracellular reducing metabolites and protein thiols. Here, we report that
      hematopoietic-derived cell lines that constitutively express HO1 are more
      susceptible to MGd-induced apoptosis than those that do not. MGd used in
      combination with tin protoporphyrin IX, an inhibitor of HO1, resulted in
      synergistic cell killing. Consistent with these cell culture observations, we
      found that MGd is an inhibitor of heme oxygenase-1 activity in vitro. We
      demonstrate that inhibition of HO1 reflects an interaction of MGd with NADPH
      cytochrome P450 reductase, the electron donor for HO1, that results in diversion
      of reducing equivalents from heme oxidation to oxygen reduction. In accord with
      this mechanism, MGd is also an in vitro inhibitor of CYP2C9, CYP3A4, and CYP4A1.
      Inhibition of HO1 by MGd may contribute to its anticancer activity, whereas its
      in vitro inhibition of a broad spectrum of P450 enzymes indicates that a
      potential exists for drug-drug interactions.

PMID- 17018579
TI  - Regulation of human cone cyclic nucleotide-gated channels by endogenous
      phospholipids and exogenously applied phosphatidylinositol 3,4,5-trisphosphate.
AB  - Cyclic nucleotide-gated (CNG) channels are critical components of the vertebrate
      visual transduction cascade involved in converting light-induced changes in
      intracellular cGMP concentrations into electrical signals that can be interpreted
      by the brain as visual information. To characterize regulatory mechanisms capable
      of altering the apparent ligand affinity of cone channels, we have expressed
      heteromeric (CNGA3 + CNGB3) human cone CNG channels in Xenopus laevis oocytes and
      characterized the alterations in channel activity that occur after patch excision
      using patch-clamp recording in the inside-out configuration. We found that cone
      channels exhibit spontaneous changes in current at subsaturating cGMP
      concentrations; these changes are enhanced by application of ATP and seem to
      reflect alterations in channel gating. Similar to rod CNG channels, lavendustin A
      prevented this regulation, suggesting the involvement of a tyrosine
      phosphorylation event. However, the tyrosine residue in CNGB3 (Tyr545) that is
      equivalent to the critical tyrosine residues in rod and olfactory CNG channel
      subunits does not participate in cone channel regulation. Furthermore, the
      changes in ligand sensitivity of CNGA3 + CNGB3 channels were prevented by
      inhibition of phosphatidylinositol 3-kinase (PI3-kinase) using wortmannin or 2-(4
      morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), which
      suggests that phospholipid metabolism can regulate the channels. Direct
      application of phosphatidylinositol 3,4,5-trisphosphate (PIP3) to the
      intracellular face of excised patches also resulted in down-regulation of channel
      activity. Thus, phospholipid metabolism and exogenously applied PIP3 can modulate
      heterologously expressed cone CNG channels.

PMID- 17018580
TI  - Risk of leukaemia among children living near the Solway coast of Dumfries and
      Galloway Health Board area, Scotland, 1975-2002.
AB  - OBJECTIVE: To investigate allegations of an excess risk of leukaemia among
      children living near the Solway Firth coast of Dumfries and Galloway Health Board
      area in Scotland, UK. METHODS: Incident cases of childhood leukaemia
      (International Classification of Diseases, 10th revision, C91-C95, patients aged
      0-14 years) for two almost equal calendar periods of diagnosis (1975-89 and 1990
      2002) were selected from the Scottish Cancer Registry database and allocated to
      predetermined study areas, on the basis of proximity of residence to the Solway
      coast. Expected numbers of childhood leukaemia cases for the study areas were
      calculated by applying Scotland's age-specific, sex-specific and calendar period
      specific rates to estimates of the person-years at risk in each study area. The
      ratios of observed to expected cases or standardised incidence ratios (SIRs) were
      calculated overall and for each sex and calendar period category. Exact 95%
      confidence intervals (CIs) for the SIRs were calculated assuming a Poisson
      distribution for the observed number of cases of childhood leukaemia. RESULTS: No
      statistically significantly increased SIRs were found in boys, girls or both
      combined for any of the areas or periods of diagnosis studied. For the total
      period of observation (1975-2002), and the more immediate coastal area studied,
      the SIR for both sexes combined was 1.22 (95% CI 0.53 to 2.40). CONCLUSION: No
      statistically significant evidence was found of an excess risk of childhood
      leukaemia in the vicinity of the Solway Firth coast of Dumfries and Galloway
      Health Board area in Scotland.

PMID- 17018581
TI  - Dose-effect relationships between manganese exposure and neurological,
      neuropsychological and pulmonary function in confined space bridge welders.
AB  - BACKGROUND: Although adverse neuropsychological and neurological health effects
      are well known among workers with high manganese (Mn) exposures in mining, ore
      processing and ferroalloy production, the risks among welders with lower
      exposures are less well understood. METHODS: Confined space welding in
      construction of a new span of the San Francisco-Oakland Bay Bridge without
      adequate protection was studied using a multidisciplinary method to identify the
      dose-effect relationship between adverse health effects and Mn in air or whole
      blood. Bridge welders (n = 43) with little or no personal protection equipment
      and exposed to a welding fume containing Mn, were administered neurological,
      neuropsychological, neurophysiological and pulmonary tests. Outcome variables
      were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index
      (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of
      16.5 months of welding on the bridge, were on average 43.8 years of age and had
      on average 12.6 years of education. RESULTS: The mean time weighted average of Mn
      air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found
      in 43% of the workers, but the concentrations of Mn in urine, lead in blood and
      copper and iron in plasma were normal. Forced expiratory volume at 1s: forced
      vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the
      welders after about 1.5 years of welding at the bridge. Mean scores of
      bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6,
      respectively. Computer assisted tremor analysis system hand tremor and body sway
      tests, and University of Pennsylvania Smell Identification Test showed impairment
      in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose
      effect relationships with CEI and/or MnB were found for IQ (p<or=0.05), executive
      function (p<or=0.03), sustaining concentration and sequencing (p<or=0.04), verbal
      learning (p<or=0.01), working (p<or=0.04) and immediate memory (p<or=0.02), even
      when adjusted for demographics and years of welding before Bay Bridge. Symptoms
      reported by the welders while working were: tremors (41.9%); numbness (60.5%);
      excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%);
      toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose
      effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05),
      depression (p<0.01) and headache (p<0.05) were statistically significant.
      CONCLUSIONS: Confined space welding was shown to be associated with neurological,
      neuropsychological and pulmonary adverse health effects. A careful enquiry of
      occupational histories is recommended for all welders presenting with
      neurological or pulmonary complaints, and a more stringent prevention strategy
      should be considered for Mn exposure due to inhalation of welding fume.

PMID- 17018582
TI  - Hay fever and asthma symptoms in conventional and organic farmers in The
      Netherlands.
AB  - BACKGROUND: Farming has been associated with respiratory symptoms and with
      protection against atopy. To date, effects of organic farming on respiratory
      health have not been studied. AIMS: To (1) compare hay fever and asthma-like
      symptoms in organic and conventional farmers and (2) assess associations between
      current and childhood farm exposures and respiratory health effects by conducting
      a survey. METHODS: Questionnaire data from 1205 conventional and 593 organic
      farmers were evaluated. Associations between health effects and farm exposures
      were assessed by logistic regression analyses. RESULTS: Organic farmers reported
      less wheezing with shortness of breath and slightly more hay fever than
      conventional farmers. However, organic farming was not an independent determinant
      of hay fever when adjusted for farming practices and potential confounders.
      Livestock farmers who grew up on a farm had a threefold lower prevalence of hay
      fever than crop farmers without a farm childhood (odds ratio (OR) 0.3, 95%
      confidence interval (CI) 0.1 to 0.5). Both crop farmers who grew up on a farm and
      livestock farmers who did not grow up on a farm had a reduced prevalence,
      although less pronounced and not statistically significant. Use of disinfectants
      containing quaternary ammonium compounds was positively related to hay fever (OR
      2.1, 95% CI 1 to 4.4). No effects of farming practices were found for asthma.
      CONCLUSIONS: Our study adds to the evidence that a farm childhood in combination
      with current livestock farming protects against allergic disorders. This effect
      was found for both organic and conventional farmers.

PMID- 17018583
TI  - Occupational risk factors for prostate cancer and benign prostatic hyperplasia: a
      case-control study in Western Australia.
AB  - OBJECTIVE: To assess the association of selected occupational exposures with risk
      of prostate cancer and with risk of benign prostatic hyperplasia (BPH). METHODS:
      This population-based case-control study recruited 606 men with a diagnosis of
      confirmed prostate cancer, 400 men who had undergone their first prostatectomy
      for BPH and 471 male controls randomly selected from the electoral roll between 1
      August 2001 and 1 October 2002 in Western Australia. chi(2) tests and logistic
      regressions were used for univariate and multivariate analyses to investigate the
      association of the two outcomes with occupational exposure to pesticides,
      fertilisers, metals, wood dust, oils, diesel exhaust and polyaromatic
      hydrocarbons (PAHs). RESULTS: Exposure to toxic metals at a non-substantial level
      increased the risk of BPH (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.1
      to 1.84) and led to a non-significant excess risk of prostate cancer (OR 1.25,
      95% CI 0.96 to 1.61). Non-significant excess risks were observed for prostate
      cancer after exposure to oils other than mineral oil (OR 1.54, 95% CI 0.95 to
      2.51) and for BPH after exposure to PAHs (OR 1.20, 95% CI 0.91 to 1.58). A non
      statistically significant protective effect for prostate cancer was seen after
      exposure to organophosphate pesticides (OR 0. 69, 95% CI 0.43 to 1.12). No other
      associations were found for either prostate cancer or BPH and no dose-response
      relationships were seen for the exposures investigated. CONCLUSIONS: These
      results do not provide evidence that any of the occupational factors examined are
      risk factors for either prostate cancer or BPH.

PMID- 17018584
TI  - Genetic interaction between Rb and N-ras: differentiation control and metastasis.
AB  - The retinoblastoma tumor suppressor gene, Rb, and the ras proto-oncogenes
      regulate various cellular processes, including differentiation and proliferation.
      Rb and ras genetically interact to positively influence differentiation in the
      mouse. This genetic interaction between Rb and ras also affects tumor
      development, either positively or negatively depending on cell type. Loss of one
      or two N-ras alleles allows medullary thyroid (C cell) adenomas occurring in Rb
      heterozygous mice to progress to metastatic carcinomas, an event associated with
      C cells displaying a less-differentiated phenotype. Here, we discuss the genetic
      interaction between Rb and ras and the development of a mouse model of medullary
      thyroid carcinoma.

PMID- 17018585
TI  - Autophagy in cancer: good, bad, or both?
AB  - Autophagy has been recognized as an important cellular process for at least 50
      years; however, it is only with the recent identification of key regulators of
      autophagy (Atg genes) that we have begun a mechanistic exploration of its
      importance in cancer. Recent studies suggest that autophagy may be important in
      the regulation of cancer development and progression and in determining the
      response of tumor cells to anticancer therapy. However, the role of autophagy in
      these processes is complicated and may, depending on the circumstances, have
      diametrically opposite consequences for the tumor. In this article, we discuss
      recent discoveries regarding autophagy in cancer.

PMID- 17018586
TI  - Enhancer of Zeste 2 as a marker of preneoplastic progression in the breast.
AB  - Amplification of the Polycomb group transcriptional repressor Enhancer of Zeste 2
      (EZH2) occurs in various malignancies including breast cancer, where its
      overexpression is associated with poor outcome. We found that EZH2 is up
      regulated in ductal carcinoma in situ, atypical ductal hyperplasia, and even
      morphologically normal breast epithelial cells from women who have an increased
      risk of breast cancer. This review discusses how EZH2 may promote neoplastic
      conversion and it surveys the evidence suggesting that EZH2 may offer a clinical
      tool to help identify patients at risk for developing breast cancer before
      precursor lesions are histologically evident.

PMID- 17018587
TI  - Inhibition of p53 response in tumor stroma improves efficacy of anticancer
      treatment by increasing antiangiogenic effects of chemotherapy and radiotherapy
      in mice.
AB  - Inactivation of p53 function, which frequently occurs in tumors, can
      significantly modulate tumor cell sensitivity to radiation and chemotherapeutic
      drugs. However, in addition to acting on malignant cells, anticancer agents act
      on the cells of tumor stroma, causing activation of a p53 response. The effect of
      this response on treatment outcome has been the subject of the present study.
      Tumors with p53-deficient stroma were generated using mouse tumorigenic packaging
      cells that produce a p53 inhibitory retrovirus, encoding a dominant-negative p53
      mutant. Tumors maintaining wild-type p53 in their stroma were formed by cells of
      similar origin but deficient in retroviral production due to the deletion of the
      packaging signal in the retroviral vector. Comparison of these tumor models,
      differing only in p53 status of their stromas, showed that tumors with p53
      deficient stroma were significantly more sensitive to experimental chemotherapy
      and radiotherapy. A similar effect was achieved when anticancer treatment was
      combined with pharmacologic suppression of p53 by the cyclic form of pifithrin
      alpha, a small-molecule inhibitor of p53. Potentiation of the anticancer effect
      of chemotherapy and radiotherapy by p53 suppression in the tumor stroma is likely
      to be due to the increased sensitivity of p53-deficient endothelium to genotoxic
      stress as shown both in cell culture and in experimental tumors. Thus, reversible
      pharmacologic suppression of p53 may be a viable approach to improving anticancer
      treatment via an enhanced antiangiogenic effect of chemotherapy and radiotherapy.

PMID- 17018589
TI  - Genomic copy number changes affecting the thymidylate synthase (TYMS) gene in
      cancer: a model for patient classification to aid fluoropyrimidine therapy.
AB  - Thymidylate synthase (TS) is an important target for 5-fluorouracil (5FU)-based
      therapy. The TS polymorphic 5'-untranslated region tandem repeat sequence is
      under investigation to guide 5FU treatment, yet current protocols omit
      consideration of copy number changes at the TS locus. We surveyed the TS tandem
      repeat sequence and found copy number changes in gastrointestinal cancers. Ten of
      12 informative cases had loss of heterozygosity (LOH), whereas two others and an
      additional cell line had a novel TS genotype, allelic imbalance at the TS locus
      due to polysomy. Experimentally, we studied a diploid colorectal cancer line
      heterozygous at TS to mimic three common TS genotypes of cancers. Using genetic
      engineering, we deleted the short tandem repeat (two repeats) allele and retained
      the long (three repeats) allele to produce artificial LOH at the TS gene; the
      TS(+/-) line had a reduced TS protein expression and was hypersensitive to 5FU
      and 5-fluoro-2'-deoxyuridine in vitro as compared with syngeneic control lines.
      We linked this sensitivity directly to the reduced TS expression by introducing
      exogenous TS cDNA expression into the TS(+/-) line (i.e., increased TS copies).
      Our model predicts that the 5FU sensitivity of a tumor is modified by aneuploidy
      producing copy number changes of TS alleles by one or more of the following: LOH,
      amplification, and, as presented here, copy number changes due to polysomy. The
      data suggest that TS copy number in a patient's tumor may be a dominating
      variable affecting 5FU responsiveness.

PMID- 17018588
TI  - Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell
      carcinoma.
AB  - p63 is essential for normal epithelial development and is overexpressed in the
      vast majority of squamous cell carcinomas (SCC). Recent work had shown that
      DeltaNp63alpha is essential for survival of SCC cells, raising the possibility
      that the p63 pathway may be an attractive therapeutic target in these tumors.
      Nevertheless, it is unknown whether a therapeutic window exists for inhibiting
      p63 in tumor cells versus normal epithelia. Here, we show that SCC cells are
      uniquely dependent on DeltaNp63alpha for survival, unlike normal p63-expressing
      epithelial cells, and that dependence is mediated through tumor-specific up
      regulation of the related protein p73. In normal primary human keratinocytes, we
      find that inhibition of endogenous p63 by RNA interference (RNAi) induces
      p21(CIP1) expression, inhibits cell cycle progression, and ultimately promotes
      cellular senescence. In contrast, p63 inhibition in SCC cells induces
      proapoptotic bcl-2 family members and rapidly triggers apoptosis. Expression of
      p73 is low in uncultured basal keratinocytes but is markedly up-regulated in both
      SCC cell lines and primary tumors in vivo. Whereas p21(CIP1) induction following
      loss of p63 in normal cells is independent of p53 and p73, both proapoptotic gene
      induction and cell death following p63 RNAi in tumor cells are p73 dependent.
      Finally, ectopic p73 expression in primary keratinocytes does not affect baseline
      cell proliferation but is sufficient to trigger cell death following loss of p63.
      Together, these findings define a specific molecular mechanism of p63 dependence
      through p73 up-regulation, and they provide a rationale for targeting the p63
      pathway as a therapeutic strategy in SCCs.

PMID- 17018590
TI  - Dietary administration of the proapoptotic vitamin E analogue alpha
      tocopheryloxyacetic acid inhibits metastatic murine breast cancer.
AB  - The ability of the vitamin E (RRR-alpha-tocopherol) derivatives alpha-tocopheryl
      succinate (alpha-TOS) and alpha-tocopheryloxyacetic acid (alpha-TEA) to suppress
      tumor growth in preclinical animal models has recently led to increased interest
      in their potential use for treating human cancer. To make the use of these
      vitamin E analogues more clinically relevant, we compared the antitumor efficacy
      of orally and i.p. delivered forms of alpha-TEA and alpha-TOS against a murine
      mammary cancer (4T1) that bears resemblance to human breast cancer because of its
      poor immunogenicity and high metastatic potential. In cell culture studies, we
      showed that both compounds inhibited tumor colony formation and induced apoptotic
      death of tumor cells. To avoid solubility concerns associated with the
      hydrophobicity of alpha-TEA and alpha-TOS, we used the vesiculated forms of alpha
      TEA (V alpha-TEA) and alpha-TOS (V alpha-TOS) for the in vivo tumor studies. Both
      compounds inhibited the growth of preestablished 4T1 tumors when given i.p.
      However, when given by oral gavage, only the esterase-resistant V alpha-TEA was
      able to suppress primary tumor growth and reduce lung metastasis. To make this
      approach more translatable to the clinic, alpha-TEA was incorporated into the
      diet and fed to tumor-bearing mice. We report here for the first time that
      dietary alpha-TEA delivery significantly inhibited primary tumor growth and
      dramatically reduced spontaneous metastatic spread to the lung in prophylactic
      and therapeutic settings. This study suggests that dietary alpha-TEA could prove
      useful as a relatively easy and effective modality for treating metastatic breast
      cancer.

PMID- 17018591
TI  - Targeted disruption of protein kinase C epsilon reduces cell invasion and
      motility through inactivation of RhoA and RhoC GTPases in head and neck squamous
      cell carcinoma.
AB  - Over 70% of patients with head and neck squamous cell carcinoma (HNSCC) present
      with locoregionally advanced stage III and IV disease. In spite of aggressive
      therapy, locoregional disease recurs in 60% and metastatic disease develops in
      15% to 25% of patients causing a major decline in quality and length of life.
      Therefore, there is a need to identify and understand genes that are responsible
      for inducing an aggressive HNSCC phenotype. Evidence has shown that protein
      kinase C (PKC) epsilon is a transforming oncogene and may play a role in HNSCC
      progression. In this study, we determine the downstream signaling pathway
      mediated by PKC epsilon to promote an aggressive HNSCC phenotype. RNA
      interference knockdown of PKC epsilon in UMSCC11A and UMSCC36, two highly
      invasive and motile HNSCC cell lines with elevated endogenous PKC epsilon levels,
      resulted in cells that were significantly less invasive and motile than the small
      interfering RNA-scrambled control transfectants; 51 +/- 5% (P < 0.006) and 49 +/-
      3% (P < 0.010) inhibition in invasion and 69 +/- 1% (P < 0.0005) and 66 +/- 3% (P
      < 0.0001) inhibition in motility, respectively. PKC epsilon-deficient UMSCC11A
      clones had reduced levels of active and serine-phosphorylated RhoA and RhoC.
      Moreover, constitutive active RhoA completely rescued the invasion and motility
      defect, whereas constitutive active RhoC completely rescued the invasion and
      partially rescued the motility defect of PKC epsilon-deficient UMSCC11A clones.
      These results indicate that RhoA and RhoC are downstream of PKC epsilon and
      critical for PKC epsilon-mediated cell invasion and motility. Our study shows,
      for the first time, that PKC epsilon is involved in a coordinated regulation of
      RhoA and RhoC activation, possibly through direct post-translational
      phosphorylation.

PMID- 17018592
TI  - TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal
      carcinoma.
AB  - In up to 87% of nasopharyngeal carcinoma (NPC) clinical tumor specimens, there
      was either down-regulation or loss of TSLC1 gene expression. Using a tissue
      microarray and immunohistochemical staining, the frequency of down-regulated or
      loss of expression of TSLC1 in metastatic lymph node NPC was 83% and the
      frequency of loss of expression of TSLC1 was 35%, which was significantly higher
      than that in primary NPC (12%). To examine the possible growth-suppressive
      activity of TSLC1 in NPC, three NPC cell lines, HONE1, HNE1, and CNE2, were
      transfected with the wild-type TSLC1 gene cloned into the pCR3.1 expression
      vector; a reduction of colony formation ability was observed for all three cell
      lines. A tetracycline-inducible expression vector, pETE-Bsd, was also used to
      obtain stable transfectants of TSLC1. There was a dramatic difference between
      colony formation ability in the presence or absence of doxycycline when the gene
      is shut off or expressed, respectively, with the tetracycline-inducible system.
      Tumorigenicity assay results show that the activation of TSLC1 suppresses tumor
      formation in nude mice and functional inactivation of this gene is observed in
      all the tumors derived from tumorigenic transfectants. Further studies indicate
      that expression of TSLC1 inhibits HONE1 cell growth in vitro by arresting cells
      in G(0)-G(1) phase in normal culture conditions, whereas in the absence of serum,
      TSLC1 induced apoptosis. These findings suggest that TSLC1 is a tumor suppressor
      gene in NPC, which is significantly associated with lymph node metastases.

PMID- 17018593
TI  - Critical roles for non-pRb targets of human papillomavirus type 16 E7 in cervical
      carcinogenesis.
AB  - High-risk human papillomaviruses (HPV) encode two oncogenes, E6 and E7, expressed
      in nearly all cervical cancers. In vivo, HPV-16 E7 has been shown to induce
      multiple phenotypes in the context of transgenic mice, including cervical cancer.
      E7 is a multifunctional protein known best for its ability to inactivate the
      tumor suppressor pRb. To determine the importance of pRb inactivation by E7 in
      cervical cancer, we pursued studies with genetically engineered mice. E7
      expression in estrogen-treated murine cervix induced dysplasia and invasive
      cancers as reported previously, but targeted Rb inactivation in cervical
      epithelium was not sufficient to induce any cervical dysplasia or neoplasia.
      Furthermore, E7 induced cervical cancer formation even when the E7-pRb
      interaction was disrupted by the use of a knock-in mouse carrying an E7-resistant
      mutant Rb allele. pRb inactivation was necessary but not sufficient for E7 to
      overcome differentiation-induced or DNA damage-induced cell cycle arrest, and
      expression patterns of the E2F-responsive genes Mcm7 and cyclin E indicate that
      other E2F regulators besides pRb are important targets of E7. Together, these
      data indicate that non-pRb targets of E7 play critical roles in cervical
      carcinogenesis.

PMID- 17018594
TI  - Deleted in colorectal cancer is a putative conditional tumor-suppressor gene
      inactivated by promoter hypermethylation in head and neck squamous cell
      carcinoma.
AB  - Deleted in colorectal cancer (DCC) is a candidate tumor-suppressor gene located
      at chromosome 18q21. However, DCC gene was found to have few somatic mutations
      and the heterozygous mice (DCC(+/-)) showed a similar frequency of tumor
      formation compared with the wild-type mice (DCC(+/+)). Recently, DCC came back to
      the spotlight as a better understating of its function and relationship with its
      ligand (netrin-1) had shown that DCC may act as a conditional tumor-suppressor
      gene. We evaluated hypermethylation as a mechanism for DCC inactivation in head
      and neck squamous cell carcinoma (HNSCC). DCC promoter region hypermethylation
      was found in 75% of primary HNSCC. There was a significant correlation between
      DCC promoter region hypermethylation and DCC expression (assessed by
      immunohistochemistry; P = 0.021). DCC nonexpressing HNSCC cell lines JHU-O12 and
      JHU-O19 with baseline hypermethylation of the DCC promoter were treated with 5
      aza-2'-deoxycytidine (a demethylating agent) and reexpression of DCC was noted.
      Transfection of DCC into DCC-negative HNSCC cell lines resulted in complete
      abrogation of growth in all cell lines, whereas additional cotransfection of
      netrin-1 resulted in rescue of DCC-mediated growth inhibition. These results
      suggest that DCC is a putative conditional tumor-suppressor gene that is
      epigenetically inactivated by promoter hypermethylation in a majority of HNSCC.

PMID- 17018595
TI  - The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1
      oncogenic signaling pathway as a therapeutic target for lung cancer.
AB  - Using a genome-wide cDNA microarray to search for genes that were specifically up
      regulated in non-small cell lung cancers (NSCLC), we identified an abundant
      expression of neuromedin U (NMU) in the great majority of lung cancers.
      Immunohistochemical analysis showed a significant association of NMU expression
      with poorer prognosis of patients with NSCLC. Treatment of NSCLC cells with short
      interfering RNA against NMU suppressed its expression and inhibited the growth of
      the cells; on the other hand, the induction of exogenous expression of NMU
      conferred growth-promoting activity and enhanced cell mobility in vitro. We found
      that two G protein-coupled receptors, growth hormone secretagogue receptor 1b and
      neurotensin receptor 1, were also overexpressed in NSCLC cells, and that a
      heterodimer complex of these receptors functioned as an NMU receptor. The NMU
      receptor interaction subsequently induced the generation of a second messenger,
      cyclic AMP, to activate its downstream genes including transcription factors and
      cell cycle regulators. Treatment of NSCLC cells with short interfering RNAs for
      growth hormone secretagogue receptor or neurotensin receptor 1 suppressed the
      expression of those genes and the growth of NSCLC cells. These data strongly
      implied that targeting the NMU signaling pathway would be a promising therapeutic
      strategy for the treatment of lung cancers.

PMID- 17018596
TI  - ERCC4 associated with breast cancer risk: a two-stage case-control study using
      high-throughput genotyping.
AB  - The failure of linkage studies to identify further high-penetrance susceptibility
      genes for breast cancer points to a polygenic model, with more common variants
      having modest effects on risk, as the most likely candidate. We have carried out
      a two-stage case-control study in two European populations to identify low
      penetrance genes for breast cancer using high-throughput genotyping. Single
      nucleotide polymorphisms (SNPs) were selected across preselected cancer-related
      genes, choosing tagSNPs and functional variants where possible. In stage 1,
      genotype frequencies for 640 SNPs in 111 genes were compared between 864 breast
      cancer cases and 845 controls from the Spanish population. In stage 2, candidate
      SNPs identified in stage 1 (nominal P < 0.01) were tested in a Finnish series of
      884 cases and 1,104 controls. Of the 10 candidate SNPs in seven genes identified
      in stage 1, one (rs744154) on intron 1 of ERCC4, a gene belonging to the
      nucleotide excision repair pathway, was associated with recessive protection from
      breast cancer after adjustment for multiple testing in stage 2 (odds ratio, 0.57;
      Bonferroni-adjusted P = 0.04). After considering potential functional SNPs in the
      region of high linkage disequilibrium that extends across the entire gene and
      upstream into the promoter region, we concluded that rs744154 itself could be
      causal. Although intronic, it is located on the first intron, in a region that is
      highly conserved across species, and could therefore be functionally important.
      This study suggests that common intronic variation in ERCC4 is associated with
      protection from breast cancer.

PMID- 17018598
TI  - Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and
      activated by amplification in squamous cell carcinomas.
AB  - Chromosomal amplification at 3q is common to multiple human cancers, but has a
      specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We
      identified and characterized a novel oncogene, SCC-related oncogene (SCCRO),
      which is amplified along the 3q26.3 region in human SCC. Amplification and
      overexpression of SCCRO in these tumors correlate with poor clinical outcome. The
      importance of SCCRO amplification in malignant transformation is established by
      the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer
      cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is
      underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and
      in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH)
      pathway. Collectively, these data suggest that SCCRO is a novel component of the
      HH signaling pathway involved in the malignant transformation of squamous cell
      lineage.

PMID- 17018597
TI  - High-resolution global genomic survey of 178 gliomas reveals novel regions of
      copy number alteration and allelic imbalances.
AB  - Primary brain tumors are the fourth leading cause of cancer mortality in adults
      under the age of 54 years and the leading cause of cancer mortality in children
      in the United States. Therapy for the most common type of primary brain tumors,
      gliomas, remains suboptimal. The development of new and more effective treatments
      will likely require a better understanding of the biology of these tumors. Here,
      we show that use of the high-density 100K single-nucleotide polymorphism arrays
      in a large number of primary tumor samples allows for a much higher resolution
      survey of the glioma genome than has been previously reported in any tumor type.
      We not only confirmed alterations in genomic areas previously reported to be
      affected in gliomas, but we also refined the location of those sites and
      uncovered multiple, previously unknown regions that are affected by copy number
      alterations (amplifications, homozygous and heterozygous deletions) as well as
      allelic imbalances (loss of heterozygosity/gene conversions). The wealth of
      genomic data produced may allow for the development of a more rational molecular
      classification of gliomas and serve as an important starting point in the search
      for new molecular therapeutic targets.

PMID- 17018599
TI  - An EBF3-mediated transcriptional program that induces cell cycle arrest and
      apoptosis.
AB  - In a genome-wide screen for putative tumor suppressor genes, the EBF3 locus on
      the human chromosome 10q26.3 was found to be deleted or methylated in 73% of the
      examined cases of brain tumors. EBF3 is expressed in normal brain but is silenced
      in brain tumors. Therefore, it is suggested that EBF3 is a tumor suppressor.
      However, it remains unknown whether inactivation of EBF3 locus also occurs in
      other types of tumors and what functions of EBF3 underlie EBF3-mediated tumor
      suppression. We show here that expression of EBF3 resulted in cell cycle arrest
      and apoptosis. The expression of cyclin-dependent kinase inhibitors was
      profoundly affected with early activation and then repression of p21(cip1/waf1)
      and persistent activation of both p27(kip1) and p57(kip2), whereas genes involved
      in cell survival and proliferation were suppressed. EBF3 bound directly to
      p21(cip1/waf1) promoter and regulated transcription from both p21(cip1/waf1) and
      p27(kip1) promoters in reporter assays. Apoptosis occurred 48 hours after EBF3
      expression with caspase-3 activation. Silencing of the EBF3 locus was observed in
      brain, colorectal, breast, liver, and bone tumor cell lines and its reactivation
      was achieved on treatment with 5-aza-2'-deoxycytidine and trichostatin A in a
      significant portion of these tumor cells. Therefore, EBF3 regulates a
      transcriptional program underlying a putative tumor suppression pathway.

PMID- 17018600
TI  - Activation of cancer cell migration and invasion by ectopic synthesis of
      coagulation factor VII.
AB  - Blood coagulation factor VII (fVII) is physiologically synthesized in the liver
      and released into the blood. Binding of fVII to tissue factor (TF) at sites of
      vascular injury triggers coagulation and hemostasis. TF/fVIIa complex formation
      on the surface of cancer cells plays important roles in cancer biology. Although
      fVII is synthesized by hepatocellular carcinoma, it remained unclear how TF/fVIIa
      complex formation and promigratory signaling can occur for most other cancers in
      extravascular locations. Here, we show by reverse transcription-PCR analysis that
      nonhepatic cancer cell lines constitutively express fVII mRNA and that
      endogenously synthesized fVIIa triggers coagulation activation on these cells.
      fVIIa expression in cancer cells is inducible under hypoxic conditions and
      hypoxia-inducible factor-2 alpha bound the promoter region of the FVII gene in
      chromatin immunoprecipitation analyses. Constitutive fVII expression in an
      ovarian cancer cell line enhanced both migration and invasion. Enhanced motility
      was blocked by anti-TF antibodies, factor Xa inhibition, and anti-protease
      activated receptor-1 antibody treatment, confirming that TF/fVIIa stimulated
      migration by triggering cell signaling. This study shows that ectopic synthesis
      of fVII by cancer cells is sufficient to support proinvasive factor Xa-mediated
      protease-activated receptor-1 signaling and that this pathway is inducible under
      hypoxia.

PMID- 17018601
TI  - Estrogen-induced activation of mammalian target of rapamycin is mediated via
      tuberin and the small GTPase Ras homologue enriched in brain.
AB  - Inhibitors of the mammalian target of rapamycin (mTOR) are currently in clinical
      trials for the treatment of breast cancer. The mechanisms through which mTOR are
      activated in breast cancer and the relationship of mTOR activation to steroid
      hormones, such as estrogen, that are known to influence breast cancer
      pathogenesis, are not yet understood. Using MCF-7 cells as a model, we found that
      17-beta estradiol (E(2)) rapidly increased the phosphorylation of downstream
      targets of mTOR: p70 ribosomal protein S6 kinase, ribosomal protein S6, and
      eukaryotic initiation factor 4E-binding protein 1. The phosphoinositide-3-kinase
      inhibitor, wortmannin, and the mTOR inhibitor, rapamycin, blocked E(2)-induced
      activation of p70 ribosomal protein S6 kinase. We hypothesized that tuberin and
      the small GTPase Ras homologue enriched in brain (Rheb), regulators of the mTOR
      pathway, mediate E(2)-induced activation of mTOR. Consistent with this
      hypothesis, E(2) rapidly (within 5 minutes) stimulated tuberin phosphorylation at
      T1462, a site at which Akt phosphorylates and inactivates tuberin. E(2) also
      rapidly decreased the inactive, GDP-bound form of Rheb. Finally, we found that
      small interfering RNA down-regulation of endogenous Rheb blocked the E(2)
      stimulated proliferation of MCF-7 cells, demonstrating that Rheb is a key
      determinant of E(2)-dependent cell growth. Taken together, these data reveal that
      the TSC/Rheb/mTOR pathway plays a critical role in the regulation of E(2)-induced
      proliferation, and highlight Rheb as a novel molecular target for breast cancer
      therapy.

PMID- 17018602
TI  - Regulation of hdm2 by stress-induced hdm2alt1 in tumor and nontumorigenic cell
      lines correlating with p53 stability.
AB  - Alternative and aberrant splicing of hdm2 occurs in tumor and normal tissues.
      However, the factors that induce these splice variants and whether they are
      translated to protein products in vivo is unknown, making it difficult to
      decipher which of these hdm2 transcripts have a normal physiologic function or
      contribute to carcinogenesis. We investigated the conditions that induce this
      post-transcriptional modification of hdm2 in tumor and nontumorigenic cell lines.
      We showed that UV and gamma radiation as well as cisplatin treatment induced
      alternative splicing of hdm2, which resulted in a single splice variant,
      hdm2(alt1), irrespective of the cell type. Interestingly, the mechanism of UV
      induced splicing is independent of p53 status. Immunoanalysis revealed that,
      after UV radiation, HDM2(ALT1) protein was expressed and interacted with HDM2
      that correlated to increased p53 protein levels and its accumulation in the
      nucleus, whereas HDM2 localized more to the cytoplasm with a decrease in its RNA
      and protein level. We propose that stress-induced HDM2(ALT1) regulates HDM2 at
      two levels, RNA and protein, further modulating the p53-HDM2 interaction or
      interactions of HDM2 with other cell cycle regulatory proteins. This kind of
      regulation may possibly restrict oncogenic functions of HDM2 and contribute to
      the many protective responses triggered by certain stress signals. Our data imply
      that HDM2(ALT1) possesses a normal physiologic function in damaged cells, perhaps
      facilitating cellular defense.

PMID- 17018603
TI  - The synovial-sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene
      (de)regulation.
AB  - Fusion of the SS18 and either one of the SSX genes is a hallmark of human
      synovial sarcoma. The SS18 and SSX genes encode nuclear proteins that exhibit
      opposite transcriptional activities. The SS18 protein functions as a
      transcriptional coactivator and is associated with the SWI/SNF complex, whereas
      the SSX proteins function as transcriptional corepressors and are associated with
      the polycomb complex. The domains involved in these opposite transcriptional
      activities are retained in the SS18-SSX fusion proteins. Here, we set out to
      determine the direct transcriptional consequences of conditional SS18-SSX2 fusion
      protein expression using complementary DNA microarray-based profiling. By doing
      so, we identified several clusters of SS18-SSX2-responsive genes, including a
      group of genes involved in cholesterol synthesis, which is a general
      characteristic of malignancy. In addition, we identified a group of SS18-SSX2
      responsive genes known to be specifically deregulated in primary synovial
      sarcomas, including IGF2 and CD44. Furthermore, we observed an uncoupling of
      EGR1, JUNB, and WNT signaling in response to SS18-SSX2 expression, suggesting
      that the SWI/SNF-associated coactivation functions of the SS18 moiety are
      impaired. Finally, we found that SS18-SSX2 expression affects histone
      modifications in the CD44 and IGF2 promoters and DNA methylation levels in the
      IGF2 imprinting control region. Together, we conclude that the SS18-SSX2 fusion
      protein may act as a so-called transcriptional "activator-repressor," which
      induces downstream target gene deregulation through epigenetic mechanisms. Our
      results may have implications for both the development and clinical management of
      synovial sarcomas.

PMID- 17018604
TI  - In melanoma, RAS mutations are accompanied by switching signaling from BRAF to
      CRAF and disrupted cyclic AMP signaling.
AB  - Melanocytes require the RAS/RAF/MEK/ERK and the cyclic AMP (cAMP) signaling
      pathways to maintain the fine balance between proliferation and differentiation.
      We have investigated how cross-talk between these pathways affects melanoma
      progression. We show that cAMP suppresses CRAF activity in melanocytes and that
      this is essential to suppress the oncogenic potential of CRAF in these cells. As
      a consequence, BRAF alone is responsible for signaling to MEK. However, when RAS
      is mutated in melanoma, the cells switch their signaling from BRAF to CRAF. This
      switch is accompanied by dysregulated cAMP signaling, a step that is necessary to
      allow CRAF to signal to MEK. Thus, a fundamental switch in RAF isoform usage
      occurs when RAS is mutated in melanoma, and this occurs in the context of
      disrupted cAMP signaling. These data have important implications for the
      development of therapeutic strategies to treat this life-threatening disease.

PMID- 17018605
TI  - Transgenic mice expressing the p75 CCAAT-displacement protein/Cut homeobox
      isoform develop a myeloproliferative disease-like myeloid leukemia.
AB  - The p75 CCAAT-displacement protein/Cut homeobox (CDP/Cux) isoform was previously
      reported to be overexpressed in human breast cancers. To investigate its
      oncogenic potential, we engineered two transgenic mouse lines expressing p75
      CDP/Cux under the control of the mouse mammary tumor virus-long terminal repeat.
      The FVB strain of mouse is generally used in the generation of mouse models for
      breast cancer. The transgene was introduced into the hprt locus of 129/Ola
      embryonic stem cells and, following germ line passage, was backcrossed onto the
      FVB and C57BL/6 mouse strains. Here, we describe the phenotype of p75 CDP/Cux
      transgenic virgin female mice of the first backcross generations. We report that
      after a long latency period, approximately 33% of mice from two independent
      transgenic lines and from backcrosses into either the FVB or the C57BL/6 strains
      succumbed to a similar disease characterized by splenomegaly, hepatomegaly, and
      frequent infiltration of leukocytes into nonhematopoietic organs like the kidneys
      and lungs. Although an excess of B or T cells was observed in three diseased
      mice, in 17 other cases, histologic and flow cytometry analyses revealed the
      expansion of a population of neutrophils in the blood, spleen, and bone marrow.
      The increase in neutrophils correlated with signs of anemia and thrombocytopenia,
      whereas there was no indication of a reactive process. Therefore, p75 CDP/Cux
      transgenic mice displayed heightened susceptibility to a disease defined as a
      myeloproliferative disease-like myeloid leukemia. These results indicate that the
      overexpression of p75 CDP/Cux could alter homeostasis in the hematopoietic
      compartment.

PMID- 17018606
TI  - Genotoxic stress induces coordinately regulated alternative splicing of the p53
      modulators MDM2 and MDM4.
AB  - The tumor suppressor protein p53 is a transcription factor that induces G(1)
      arrest of the cell cycle and/or apoptosis. The murine double-minute protein MDM2
      and its homologue MDM4 (also known as MDMX) are critical regulators of p53.
      Altered transcripts of the human homologue of mdm2, MDM2, have been identified in
      human tumors, such as invasive carcinoma of the breast, lung carcinoma, and
      liposarcoma. MDM2 alternate forms act to negatively regulate the normal MDM2 gene
      product, thus activating p53. Although many reports have documented a plethora of
      tumor types characterized by MDM2 alternative transcripts, few have investigated
      the signals that might initiate alternative splicing. We have identified a novel
      role of these alternative MDM2 transcripts in the normal surveillance mechanism
      of the cell and in DNA damage response. We report that alternate forms of MDM2
      are detected after UV irradiation. Furthermore, we show that mouse cells treated
      with UV are also characterized by alternative transcripts of mdm2, suggesting
      that this is an important and evolutionarily conserved mechanism for regulating
      the expression of MDM2/mdm2. An additional p53 regulator and mdm2 family member,
      MDM4, is likewise alternatively spliced following UV irradiation. By activating
      alternative splicing of both MDM2 and MDM4, yet another layer of p53 regulation
      is initiated by the cells in response to damage. A stepwise model for malignant
      conversion by which alternate forms of MDM2 and MDM4 place selective pressure on
      the cells to acquire additional alterations in the p53 pathway is herein
      proposed.

PMID- 17018607
TI  - Ras-induced modulation of CXCL10 and its receptor splice variant CXCR3-B in MDA
      MB-435 and MCF-7 cells: relevance for the development of human breast cancer.
AB  - Interactions between chemokines and chemokine receptors have been proposed
      recently to be of importance in the development and progression of cancer. Human
      breast cancer cells express the chemokine CXCL10 (IP-10) and also its receptor
      CXCR3. In this study, we have investigated the role of Ras activation in the
      regulation of CXCL10 and its receptor splice variant CXCR3-B in two human breast
      cancer cell lines MDA-MB-435 and MCF-7. In cotransfection assays, using a full
      length CXCL10 promoter-luciferase construct, we found that the activated form of
      Ras, Ha-Ras(12V), promoted CXCL10 transcriptional activation. Ras significantly
      increased CXCL10 mRNA and protein expression as observed by real-time PCR,
      fluorescence-activated cell sorting analysis, and ELISA. Selective inhibition of
      Ha-Ras by small interfering RNA (siRNA) decreased CXCL10 mRNA expression in a
      dose-dependent manner. Further, using effector domain mutants of Ras, we found
      that Ras-induced overexpression of CXCL10 is mediated primarily through the Raf
      and phosphatidylinositol 3-kinase signaling pathways. We also observed that the
      expression of the splice variant CXCR3-B, known to inhibit cell proliferation,
      was significantly down-regulated by Ras. Selective inhibition of CXCR3-B using
      siRNA resulted in an increase in CXCL10-mediated breast cancer cell proliferation
      through G(i) proteins and likely involving CXCR3-A. Finally, we observed intense
      expression of CXCL10 and CXCR3 in association with human breast cancer in situ,
      indicating that these observations may be of pathophysiologic significance.
      Together, these results suggest that activation of Ras plays a critical role in
      modulating the expression of both CXCL10 and CXCR3-B, which may have important
      consequences in the development of breast tumors through cancer cell
      proliferation.

PMID- 17018608
TI  - Oxidative stress induces ADAM9 protein expression in human prostate cancer cells.
AB  - The ADAM (a disintegrin and metalloprotease) family is a group of transmembrane
      proteins containing cell adhesive and proteolytic functional domains. Microarray
      analysis detected elevated ADAM9 during the transition of human LNCaP prostate
      cancer cells from an androgen-dependent to an androgen-independent and metastatic
      state. Using a prostate tissue array (N = 200), the levels of ADAM9 protein
      expression were also elevated in malignant as compared with benign prostate
      tissues. ADAM9 protein expression was found in 43% of benign glands with light
      staining and 87% of malignant glands with increasing intensity of staining. We
      found that ADAM9 mRNA and protein expressions were elevated on exposure of human
      prostate cancer cells to stress conditions such as cell crowding, hypoxia, and
      hydrogen peroxide. We uncovered an ADAM9-like protein, which is predominantly
      induced together with the ADAM9 protein by a brief exposure of prostate cancer
      cells to hydrogen peroxide. Induction of ADAM9 protein in LNCaP or C4-2 cells can
      be completely abrogated by the administration of an antioxidant, ebselen, or
      genetic transfer of a hydrogen peroxide degradative enzyme, catalase, suggesting
      that reactive oxygen species (ROS) are a common mediator. The induction of ADAM9
      by stress can be inhibited by both actinomycin D and cycloheximide through
      increased gene transcription and protein synthesis. In conclusion, intracellular
      ROS and/or hydrogen peroxide, generated by cell stress, regulate ADAM9
      expression. ADAM9 could be responsible for supporting prostate cancer cell
      survival and progression. By decreasing ADAM9 expression, we observed apoptotic
      cell death in prostate cancer cells.

PMID- 17018609
TI  - HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers
      epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is increasingly recognized as a mechanism
      whereby cells in primary noninvasive tumors acquire properties essential for
      migration and invasion. Microarray analyses of microdissected epithelial cells
      from bone metastasis revealed a HOXB7 overexpression that was 3-fold higher than
      in primary breast carcinomas and 18-fold higher compared with normal breast. This
      led us to investigate the role of HOXB7 in neoplastic transformation of breast
      cells. Expression of HOXB7 in both MCF10A and Madin-Darby canine kidney (MDCK)
      epithelial cells resulted in the acquisition of both phenotypic and molecular
      attributes typical of EMT. Loss of epithelial proteins, claudin 1 and claudin 7,
      mislocalization of claudin 4 and E-cadherin, and the expression of mesenchymal
      proteins, vimentin and alpha-smooth muscle actin, were observed. MDCK cells
      expressing HOXB7 exhibited properties of migration and invasion. Unlike MDCK
      vector-transfected cells, MDCK-HOXB7 cells formed highly vascularized tumors in
      mice. MDCK-HOXB7 cells overexpressed basic fibroblast growth factor (bFGF), had
      more active forms of both Ras and RhoA proteins, and displayed higher levels of
      phosphorylation of p44 and p42 mitogen-activated protein kinase (MAPK;
      extracellular signal-regulated kinases 1 and 2). Effects initiated by HOXB7 were
      reversed by specific inhibitors of FGF receptor and the Ras-MAPK pathways. These
      data provide support for a function for HOXB7 in promoting tumor invasion through
      activation of Ras/Rho pathway by up-regulating bFGF, a known transcriptional
      target of HOXB7. Reversal of these effects by HOXB7-specific siRNA further
      suggested that these effects were mediated by HOXB7. Thus, HOXB7 overexpression
      caused EMT in epithelial cells, accompanied by acquisition of aggressive
      properties of tumorigenicity, migration, and invasion.

PMID- 17018610
TI  - Increased fibroblast growth factor-inducible 14 expression levels promote glioma
      cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient
      outcome.
AB  - Glial tumors progress to malignant grades by heightened proliferation and
      relentless dispersion throughout the central nervous system. Understanding
      genetic and biochemical processes that foster these behaviors is likely to reveal
      specific and effective targets for therapeutic intervention. Our current report
      shows that the fibroblast growth factor-inducible 14 (Fn14), a member of the
      tumor necrosis factor (TNF) receptor superfamily, is expressed at high levels in
      migrating glioma cells in vitro and invading glioma cells in vivo. Forced Fn14
      overexpression stimulates glioma cell migration and invasion, and depletion of
      Rac1 by small interfering RNA inhibits this cellular response. Activation of Fn14
      signaling by the ligand TNF-like weak inducer of apoptosis (TWEAK) stimulates
      migration and up-regulates expression of Fn14; this TWEAK effect requires Rac1
      and nuclear factor-kappaB (NF-kappaB) activity. The Fn14 promoter region contains
      NF-kappaB binding sites, which mediate positive feedback causing sustained
      overexpression of Fn14 and enduring glioma cell invasion. Furthermore, Fn14 gene
      expression levels increase with glioma grade and inversely correlate with patient
      survival. These results show that the Fn14 cascade operates as a positive
      feedback mechanism for elevated and sustained Fn14 expression. Such a feedback
      loop argues for aggressive targeting of the Fn14 axis as a unique and specific
      driver of glioma malignant behavior.

PMID- 17018611
TI  - Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a
      distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal
      transition.
AB  - The transcription factors Snail, Slug, and bHLH E47 have been recently described
      as direct repressors of E-cadherin and inducers of epithelial-mesenchymal
      transition (EMT) and invasion when overexpressed in epithelial cells. Although a
      role of those factors in tumor progression and invasion has been proposed,
      whether the different repressors play distinct or redundant roles in the
      tumorigenic process has not been established. To further investigate this
      important issue, we have analyzed the gene expression profiling of Madin-Darby
      canine kidney (MDCK) epithelial cells expressing the different repressors (MDCK
      Snail, MDCK-Slug, and MDCK-E47 cells) versus control MDCK cells by cDNA
      microarrays. A total of 243 clones (228 genes and 15 expressed sequence tags)
      were found to be differentially expressed between either of the three MDCK
      derived cell lines and control MDCK cells. Twenty two of the candidate genes were
      validated by Northern blot, Western blot, immunofluorescence, and promoter
      analyses in cell lines and by immunohistochemistry in xenografted tumors. Gene
      clustering analysis indicated that about a third of the 243 candidate genes were
      common to MDCK cells expressing Snail, Slug, or E47 factors, whereas the rest of
      the genes were regulated in only one or two cell types. Differentially regulated
      genes include those related to EMT (45 genes), transcriptional regulation (18
      genes), cell proliferation and signaling (54 genes), apoptosis (12 genes), and
      angiogenesis (9 genes). These results indicate that Snail, Slug, and E47
      transcription factors induce common and specific genetic programs, supporting a
      differential role of the factors in tumor progression and invasion.

PMID- 17018612
TI  - Absence of CD9 enhances adhesion-dependent morphologic differentiation, survival,
      and matrix metalloproteinase-2 production in small cell lung cancer cells.
AB  - While adhering to extracellular matrix proteins in vitro and in vivo, small cell
      lung cancer (SCLC) cells frequently show morphologic differentiation and are
      protected from apoptosis. Integrin beta(1)-mediated protein phosphorylation is
      suggested to be an essential signaling event in these processes. CD9 is an almost
      ubiquitously expressed tetraspanin protein that suppresses tumor progression by
      regulating cell motility and signaling through complex formation with beta(1)
      integrins. We reported previously that, among tetraspanins, CD9 is selectively
      absent in most SCLC cells and that ectopic expression of CD9 suppresses their
      motility. Here, we show that the ectopic expression of CD9 suppressed neurite
      like process outgrowth and promoted apoptotic death of SCLC cells that were
      adherent to fibronectin in serum-starved conditions. This correlated with
      attenuation of adhesion-dependent phosphorylation of Akt but not that of focal
      adhesion kinase or c-Jun NH(2)-terminal kinase. Treatment of CD9(-) parent cells
      with a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, inhibited
      process outgrowth and survival, suggesting that PI3K/Akt signaling is required
      for the morphologic change and cell survival. Production of matrix
      metalloproteinase (MMP)-2 was likewise suppressed in the CD9 transfectants and in
      LY294002-treated parent cells. These results suggest that the absence of CD9 in
      SCLC cells may contribute to postadhesive morphologic differentiation, survival,
      and MMP-2 production via PI3K/Akt pathway.

PMID- 17018613
TI  - Tumor-induced activation of lymphatic endothelial cells via vascular endothelial
      growth factor receptor-2 is critical for prostate cancer lymphatic metastasis.
AB  - Prostate cancer disseminates initially and primarily to regional lymph nodes.
      However, the nature of interactions between tumor cells and lymphatic endothelial
      cells (LEC) is poorly understood. In the current study, we have isolated prostate
      LECs and developed a series of two-dimensional and three-dimensional in vitro
      coculture systems and in vivo orthotopic prostate cancer models to investigate
      the interactions of prostate cancer cells with prostate LECs. In vitro, highly
      lymph node metastatic prostate cancer cell lines (PC-3 and LNCaP) and their
      conditioned medium enhanced prostate LEC tube formation and migration, whereas
      poorly lymph node metastatic prostate cancer cells (DU145) or normal prostate
      epithelial cells (RWPE-1) or their conditioned medium had no effect. In vivo, the
      occurrence of lymphatic invasion and lymph node metastasis was observed in PC-3
      and LNCaP xenografts but not in DU145 xenografts. Furthermore, vascular
      endothelial growth factor (VEGF) receptor (VEGFR)-2 is expressed by prostate
      LECs, and its ligands VEGF-A, VEGF-C, and VEGF-D are up-regulated in highly lymph
      node metastatic prostate cancer cells. Recombinant VEGF-A and VEGF-C, but not
      VEGF-C156S, potently promoted prostate LEC tube formation, migration, and
      proliferation in vitro, indicating that signaling via VEGFR-2 rather than VEGFR-3
      is involved in these responses. Consistent with this, blockade of VEGFR-2
      significantly reduced tumor-induced activation of LECs. These results show that
      the interaction of prostate tumor cells with LECs via VEGFR-2 modulates LEC
      behavior and is related to the ability of tumor cells to form lymph node
      metastases.

PMID- 17018614
TI  - The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth
      of colon carcinoma in the liver.
AB  - The chemokine receptor CXCR5 is expressed by B cells and certain T cells and
      controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is
      present in lymph nodes and spleen and also in the liver. Surprisingly, we
      detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was
      particularly prominent in pancreatic carcinoma cell lines and was also detected
      by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression
      in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost
      when cells were explanted in vitro. CXCL13 strongly promoted proliferation of
      CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic
      injection, these CXCR5 transfectants initially grew faster than controls, but the
      growth rate of control tumors accelerated later to become similar to the
      transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5
      function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL
      "intrakine," had no effect on initial growth of liver foci but later caused a
      prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and
      intrakine-transfected cells grew at similar rates as controls. We conclude that
      expression of CXCR5 on tumor cells promotes the growth of tumor cells in the
      liver and, at least for CT26 cells, seems to be required for outgrowth to large
      liver tumors. Given the limited expression on normal cells, CXCR5 may constitute
      an attractive target for therapy, particularly for pancreatic carcinoma.

PMID- 17018615
TI  - In vivo and in vitro evidence for transforming growth factor-beta1-mediated
      epithelial to mesenchymal transition in esophageal adenocarcinoma.
AB  - There is increasing evidence that epithelial to mesenchymal transition (EMT) is
      involved in cancer progression. Because local invasion and metastasis occurs
      early in the pathogenesis of esophageal adenocarcinoma, we hypothesized that EMT
      may be important in this disease. Using immunohistochemistry in a well
      characterized set of adenocarcinoma tissues, we showed down-regulation of
      epithelial markers (E-cadherin and cytokeratin 18) and up-regulation of
      mesenchymal markers (vimentin and alpha-smooth muscle actin) with concomitant
      transforming growth factor-beta1 (TGF-beta1) expression at the invasive margin
      compared with the central tumor. A panel of esophageal cell lines was examined
      for the ability of TGF-beta1 to induce EMT in vitro. TE7 cells were selected as a
      model because TGF-beta1 (0-5 ng/mL) treatment induced morphologic and molecular
      expression changes suggestive of EMT. In TE7 cells, these TGF-beta1-induced
      changes were reversed by 100 ng/mL of bone morphogenetic protein 7 (BMP7),
      another member of the TGF-beta1 superfamily. EMT was mediated via canonical TGF
      beta1 signaling with concomitant up-regulation of SMAD-interacting protein 1.
      Alterations in functional variables (aggregation, wounding, motility, and
      invasion) following TGF-beta1 treatment were consistent with a more invasive
      phenotype. These functional changes were reversed by BMP7 and SMAD4 RNA
      interference in vitro. These data suggest that TGF-beta1-mediated EMT may be
      relevant in esophageal carcinogenesis.

PMID- 17018616
TI  - HER2/Neu (ErbB2) signaling to Rac1-Pak1 is temporally and spatially modulated by
      transforming growth factor beta.
AB  - In HER2 (ErbB2)-overexpressing cells, transforming growth factor beta (TGF-beta),
      via activation of phosphoinositide-3 kinase (PI3K), recruits actin and actinin to
      HER2, which then colocalizes with Vav2, activated Rac1, and Pak1 at cell
      protrusions. This results in prolonged Rac1 activation, enhanced motility and
      invasiveness, Bad phosphorylation, uncoupling of Bad/Bcl-2, and enhanced cell
      survival. The recruitment of the HER2/Vav2/Rac1/Pak1/actin/actinin complex to
      lamellipodia was abrogated by actinin siRNAs, dominant-negative (dn) p85,
      gefitinib, and dn-Rac1 or dn-Pak1, suggesting that the reciprocal interplay of
      PI3K, HER2 kinase, and Rac GTPases with the actin cytoskeleton is necessary for
      TGF-beta action in oncogene-overexpressing cells. Thus, by recruiting the actin
      skeleton, TGF-beta "cross-links" this signaling complex at cell lamellipodia;
      this prolongs Rac1 activation and increases metastatic properties and survival of
      HER2-overexpressing cells.

PMID- 17018617
TI  - Non-small-cell lung cancers with kinase domain mutations in the epidermal growth
      factor receptor are sensitive to ionizing radiation.
AB  - Non-small cell lung cancers (NSCLCs) bearing mutations in the tyrosine kinase
      domain (TKD) of the epidermal growth factor receptor (EGFR) often exhibit
      dramatic sensitivity to the EGFR tyrosine kinase inhibitors gefitinib and
      erlotinib. Ionizing radiation (IR) is frequently used in the treatment of NSCLC,
      but little is known how lung tumor-acquired EGFR mutations affect responses to
      IR. Because this is of great clinical importance, we investigated and found that
      clonogenic survival of mutant EGFR NSCLCs in response to IR was reduced 500- to
      1,000-fold compared with wild-type (WT) EGFR NSCLCs. Exogenous expression of
      either the L858R point mutant or the DeltaE746-E750 deletion mutant form of EGFR
      in immortalized human bronchial epithelial cells, p53 WT NSCLC (A549), or p53
      null NSCLC (NCI-H1299) resulted in dramatically increased sensitivity to IR. We
      show that the majority of mutant EGFR NSCLCs, including those that contain the
      secondary gefitinib resistance T790M mutation, exhibit characteristics consistent
      with a radiosensitive phenotype, which include delayed DNA repair kinetics,
      defective IR-induced arrest in DNA synthesis or mitosis, and pronounced increases
      in apoptosis or micronuclei. Thus, understanding how activating mutations in the
      TKD domain of EGFR contribute to radiosensitivity should provide new insight into
      effective treatment of NSCLC with radiotherapy and perhaps avoid emergence of
      single agent drug resistance.

PMID- 17018618
TI  - Distinct effects of annexin A7 and p53 on arachidonate lipoxygenation in prostate
      cancer cells involve 5-lipoxygenase transcription.
AB  - Tumor suppressor function for Annexin A7 (ANXA7; 10q21) is based on cancer-prone
      phenotype in Anxa7(+/-) mouse and ANXA7 prognostic role in human cancers. Because
      ANXA7-caused liposome aggregation can be promoted by arachidonic acid (AA), we
      hypothesized that the phospholipid-binding tumor suppressor ANXA7 is associated
      with AA cascade. In a comparative study of ANXA7 versus canonical tumor
      suppressor p53 effects on AA lipoxygenation pathway in the p53-mutant and
      androgen-insensitive DU145 prostate cancer cells, both tumor suppressors altered
      gene expression of major 5-lipoxygenase (LOX) and 15-LOXs, including response to
      T helper 2 (Th2)-cytokine [interleukin-4 (IL-4)] and endogenous steroids
      (mimicked by dexamethasone). Wild-type and mutant ANXA7 distinctly affected
      expression of the dexamethasone-induced 15-LOX-2 (a prostate-specific endogenous
      tumor suppressor) as well as the IL-4-induced 15-LOX-1. On the other hand, wild
      type p53 restored 5-LOX expression in DU145 to levels comparable to benign
      prostate epithelial cells. Using mass spectrometry of DNA affinity-enriched
      nuclear proteins, we detected different proteins that were bound to adjacent p53
      and estrogen response elements in the 5-LOX promoter in DU145 cells introduced
      with ANXA7 versus p53. Sex hormone regulator 17-beta hydroxysteroid dehydrogenase
      4 was identified under p53 introduction, which induced the 5-LOX expression.
      Meantime, nuclear proteins bound to the same 5-LOX promoter site under
      introduction of ANXA7 (that was associated with the repressed 5-LOX) were
      identified as zinc finger proteins ZNF433 and Aiolos, pyrin domain-containing
      NALP10, and the p53-regulating DNA repair enzyme APEX1. Thus, ANXA7 and p53 can
      distinctly regulate LOX transcription that is potentially relevant to the AA
      mediated cell growth control in tumor suppression.

PMID- 17018619
TI  - Targeting the lymphotoxin-beta receptor with agonist antibodies as a potential
      cancer therapy.
AB  - The lymphotoxin-beta receptor (LT beta R) is a tumor necrosis factor receptor
      family member critical for the development and maintenance of various lymphoid
      microenvironments. Herein, we show that agonistic anti-LT beta R monoclonal
      antibody (mAb) CBE11 inhibited tumor growth in xenograft models and potentiated
      tumor responses to chemotherapeutic agents. In a syngeneic colon carcinoma tumor
      model, treatment of the tumor-bearing mice with an agonistic antibody against
      murine LT beta R caused increased lymphocyte infiltration and necrosis of the
      tumor. A pattern of differential gene expression predictive of cellular and
      xenograft response to LT beta R activation was identified in a panel of colon
      carcinoma cell lines and when applied to a panel of clinical colorectal tumor
      samples indicated 35% likelihood a tumor response to CBE11. Consistent with this
      estimate, CBE11 decreased tumor size and/or improved long-term animal survival
      with two of six independent orthotopic xenografts prepared from surgical
      colorectal carcinoma samples. Targeting of LT beta R with agonistic mAbs offers a
      novel approach to the treatment of colorectal and potentially other types of
      cancers.

PMID- 17018620
TI  - PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and
      in vivo.
AB  - We show here that PRL-3 protein is expressed in fetal heart, developing blood
      vessels, and pre-erythrocytes but not in their mature counterparts. These
      observations imply that PRL-3 may be involved in the early development of the
      circulatory system. Because PRL-3 mRNA had been reported to be consistently
      elevated in metastatic samples derived from colorectal cancers, we attempted to
      investigate if PRL-3 might be involved in tumor angiogenesis and if PRL-3
      expressing cells could cross-talk to human umbilical vascular endothelial cells
      (HUVEC) by using an in vitro coculture system. HUVECs were grown with
      fibroblasts, which were later overlaid with PRL-3-expressing cells. We observed
      that both PRL-3-expressing Chinese hamster ovary (CHO) cells and PRL-3-expressing
      DLD-1 human colon cancer cells could redirect the migration of HUVECs toward
      them; in addition, PRL-3-expressing DLD-1 cells could enhance HUVEC vascular
      formation. In vivo injection of PRL-3-expressing CHO cells into nude mice to form
      local tumors resulted in the recruitment of host endothelial cells into the
      tumors and initiation of angiogenesis. We further showed that PRL-3-expressing
      cells reduced interleukin-4 (IL-4) expression levels and thus attenuated IL-4
      inhibitory effects on the HUVEC vasculature. Our findings provide direct evidence
      that PRL-3 may be involved in triggering angiogenesis and establishing
      microvasculature and it may serve as an attractive therapeutic target with
      respect to both angiogenesis and cancer metastasis.

PMID- 17018621
TI  - Enhanced killing of melanoma cells by simultaneously targeting Mcl-1 and NOXA.
AB  - By deciphering the dysregulation of apoptosis in melanoma cells, new treatment
      approaches exploiting aberrant control mechanisms regulating cell death can be
      envisioned. Among the Bcl-2 family, a BH3-only member, NOXA, functions in a
      specific mitochondrial-based cell death pathway when melanoma cells are exposed
      to a proteasome inhibitor (e.g., bortezomib). Some therapeutic agents, such as
      bortezomib, not only induce proapoptotic Bcl-2 family members and active
      conformational changes in Bak and Bax but also are associated with undesirable
      effects, including accumulation of antiapoptotic proteins, such as Mcl-1. To
      enhance the bortezomib-mediated killing of melanoma cells, the apoptotic pathway
      involving NOXA was further investigated, leading to identification of an
      important target (i.e., the labile Bcl-2 homologue Mcl-1 but not other survival
      proteins). To reduce Mcl-1 levels, melanoma cells were pretreated with several
      different agents, including Mcl-1 small interfering RNA (siRNA), UV light, or the
      purine nucleoside analogue fludarabine. By simultaneously triggering production
      of NOXA (using bortezomib) as well as reducing Mcl-1 levels (using siRNA, UV
      light, or fludarabine), significantly enhanced killing of melanoma cells was
      achieved. These results show binding interactions between distinct Bcl-2 family
      members, such as NOXA and Mcl-1, in melanoma cells, paving the way for novel and
      rational therapeutic combination strategies, which target guardians of the
      proapoptotic Bak- and Bax-mediated pathways, against this highly aggressive and
      often fatal malignancy.

PMID- 17018622
TI  - Small-molecule MDM2 antagonists as a new therapy concept for neuroblastoma.
AB  - Circumvention of the p53 tumor suppressor barrier in neuroblastoma is rarely
      caused by TP53 mutation but might arise from inappropriately increased activity
      of its principal negative regulator MDM2. We show here that targeted disruption
      of the p53-MDM2 interaction by the small-molecule MDM2 antagonist nutlin-3
      stabilizes p53 and selectively activates the p53 pathway in neuroblastoma cells
      with wild-type p53, resulting in a pronounced antiproliferative and cytotoxic
      effect through induction of G(1) cell cycle arrest and apoptosis. A nutlin-3
      response was observed regardless of MYCN amplification status. Remarkably,
      surviving SK-N-SH cells adopted a senescence-like phenotype, whereas CLB-GA and
      NGP cells underwent neuronal differentiation. p53 dependence of these alternative
      outcomes of nutlin-3 treatment was evidenced by abrogation of the effects when
      p53 was knocked down by lentiviral-mediated short hairpin RNA interference. The
      diversity of cellular responses reveals pleiotropic mechanisms of nutlins to
      disable neuroblastoma cells and exemplifies the feasibility of exploiting, by a
      single targeted intervention, the multiplicity of anticancer activities exerted
      by a key tumor suppressor as p53. The observed treatment effects without the need
      of imposing a genotoxic burden suggest that selective MDM2 antagonists might be
      beneficial for treatment of neuroblastoma patients with and without MYCN
      amplification.

PMID- 17018623
TI  - Activation of aminoflavone (NSC 686288) by a sulfotransferase is required for the
      antiproliferative effect of the drug and for induction of histone gamma-H2AX.
AB  - Aminoflavone (AF) is entering clinical trials. We recently reported that AF
      induces DNA-protein cross-links (DPC) and gamma-H2AX in MCF-7 human breast cancer
      cells. To elucidate the mechanism of action of AF and provide biomarkers
      indicative of AF activity, we correlated AF activity profile (GI(50)) with gene
      expression patterns in the NCI-60 cell lines. Sulfotransferases (SULT) showed the
      highest positive correlation coefficients among approximately 14,000 probe sets
      analyzed (r = 0.537, P < 0.001). Stable transfection of SULT1A1 into AF-resistant
      MDA-MB-231 cells sensitized these cells to AF. AF produced DPCs, gamma-H2AX foci,
      and S-phase arrest in the SULT1A1-transfected but not in the parent MDA-MB-231
      cells. Conversely, cells in which SULT1A1 was knocked down by small interfering
      RNA failed to induce gamma-H2AX. Inhibition of SULTs and cytochrome P450 (CYP)
      enzymes by natural flavonoids blocked the antiproliferative activity of AF and
      the formation of AF-DNA adducts. AF also induces SULT1A1 and CYP expression in
      MCF-7 cells, suggesting the existence of an aryl hydrocarbon receptor-mediated
      positive feedback for AF activation by CYP and SULT1A1. Metabolism studies showed
      that AF can be oxidized by CYP at two amino groups to form N-hydroxyl metabolites
      that are substrates for bioactivation by SULTs. We propose that both N-sulfoxy
      groups can be further converted to nitrenium ions that form adducts with DNA and
      proteins. The results reported here show the importance of SULT1A1 and CYP for AF
      activation and anticancer activity. They also suggest using SULT1A1 and gamma
      H2AX as biomarkers for prediction of AF activity during patient selection and
      monitoring of clinical trials.

PMID- 17018624
TI  - Host and direct antitumor effects and profound reduction in tumor metastasis with
      selective EP4 receptor antagonism.
AB  - Prostaglandin E(2) (PGE(2)), one of the major metabolites of cyclooxygenase-2,
      has been implicated in tumorigenesis and tumor progression in several human
      cancers, including colorectal and lung. Here, we show that one of the PGE(2)
      receptors, the EP4 receptor, plays an important role in metastasis in both of
      these tumor types. Using i.v. injected Lewis lung carcinoma (3LL), we found that
      tumor metastasis to lung was significantly reduced when mice were treated with a
      specific EP4 antagonist ONO-AE3-208 or when EP4 receptor expression was knocked
      down in the tumor cells using RNA interference technology. Host EP4 receptors
      also contributed to tumor metastasis and tumor growth with decreased metastasis
      and tumor growth observed in EP4 receptor knockout animals. In vitro tumor cell
      adhesion, motility, invasion, colony formation, and Akt phosphorylation were all
      significantly inhibited when 3LL cells were treated with the EP4 receptor
      specific antagonist. When the cells were treated with an EP4-specific agonist
      (AE1-734), we observed a worsening of these same features in vitro. Treatment
      with ONO-AE3-208 also profoundly decreased liver metastases after intrasplenic
      injection of MC26 colon cancer cells. Our data show that selective antagonism of
      EP4 receptor signaling results in a profound reduction in lung and colon cancer
      metastasis. Selective antagonism of the EP4 receptor may thus represent a novel
      therapeutic approach for the treatment of cancer and especially its propensity to
      metastasize.

PMID- 17018625
TI  - In vitro and in vivo characterization of 64Cu-labeled Abegrin, a humanized
      monoclonal antibody against integrin alpha v beta 3.
AB  - Abegrin (MEDI-522 or Vitaxin), a humanized monoclonal antibody against human
      integrin alpha(v)beta(3), is in clinical trials for cancer therapy. In vivo
      imaging using Abegrin-based probes is needed for better treatment monitoring and
      dose optimization. Here, we conjugated Abegrin with macrocyclic chelating agent
      1,4,7,10-tetra-azacylododecane N,N',N'',N'''-tetraacetic (DOTA) at five different
      DOTA/Abegrin ratios. The conjugates were labeled with (64)Cu (half-life = 12.7
      hours) and tested in three human (U87MG, MDA-MB-435, and PC-3) and one mouse (GL
      26) tumor models. The in vitro and in vivo effects of these (64)Cu-DOTA-Abegrin
      conjugates were evaluated. The number of DOTA per Abegrin varied from 1.65 +/-
      0.32 to 38.53 +/- 5.71 and the radiolabeling yield varied from 5.20 +/- 3.16% to
      88.12 +/- 6.98% (based on 2 mCi (64)Cu per 50 microg DOTA-Abegrin conjugate). No
      significant difference in radioimmunoreactivity was found among these conjugates
      (between 59.78 +/- 1.33 % and 71.13 +/- 2.58 %). Micro-positron emission
      tomography studies revealed that (64)Cu-DOTA-Abegrin (1,000:1) had the highest
      tumor activity accumulation (49.41 +/- 4.54% injected dose/g at 71-hour
      postinjection for U87MG tumor). The receptor specificity of (64)Cu-DOTA-Abegrin
      was confirmed by effective blocking of MDA-MB-435 tumor uptake with
      coadministration of nonradioactive Abegrin. (64)Cu-DOTA-IgG exhibited background
      level tumor uptake at all time points examined. Integrin alpha(v)beta(3)-specific
      tumor imaging using (64)Cu-DOTA-Abegrin may be translated into the clinic to
      characterize the pharmacokinetics, tumor targeting efficacy, dose optimization,
      and dose interval of Abegrin and/or Abegrin conjugates. Chemotherapeutics or
      radiotherapeutics using Abegrin as the delivering vehicle may also be effective
      in treating integrin alpha(v)beta(3)-positive tumors.

PMID- 17018626
TI  - The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced
      resistance in human non-small-cell lung cancer cells.
AB  - NPRL2 is one of the novel candidate tumor suppressor genes identified in the
      human chromosome 3p21.3 region. The NPRL2 has shown potent tumor suppression
      activity in vitro and in vivo and has been suggested to be involved in DNA
      mismatch repair, cell cycle checkpoint signaling, and regulation of the apoptotic
      pathway. In this study, we analyzed the endogenous expression of the NPRL2
      protein and the cellular response to cisplatin in 40 non-small-cell lung cancer
      cell lines and found that expression of NPRL2 was significantly and reciprocally
      correlated to cisplatin sensitivity, with a Spearman correlation coefficient of 
      0.677 (P < 0.00001). Exogenously introduced expression of NPRL2 by N-[1-(2,3
      dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate:cholesterol nanoparticle
      mediated gene transfer significantly resensitized the response to cisplatin,
      yielding a 40% greater inhibition of tumor cell viability and resulting in a 2-
      to 3-fold increase in induction of apoptosis by activation of multiple caspases
      in NPRL2-transfected cells compared with untransfected cells at an equal dose of
      cisplatin. Furthermore, a systemic treatment with a combination of NPRL2
      nanoparticles and cisplatin in a human H322 lung cancer orthotopic mouse model
      significantly enhanced the therapeutic efficacy of cisplatin and overcame
      cisplatin-induced resistance (P < 0.005). These findings implicate the potential
      of NPRL2 as a biomarker for predicting cisplatin response in lung cancer patients
      and as a molecular therapeutic agent for enhancing response and resensitizing
      nonresponders to cisplatin treatment.

PMID- 17018627
TI  - The COOH-terminal globular domain of fibrinogen gamma chain suppresses
      angiogenesis and tumor growth.
AB  - Fibrinogen is a major plasma protein (350 kDa) that induces proliferative signals
      by serving as a scaffold to support the binding of growth factors and to promote
      the cellular responses of adhesion, proliferation, and migration during wound
      healing, angiogenesis, and tumor growth. Fibrin(ogen) degradation products
      generated during fibrinolysis are implicated in tissue injury. The fibrinogen
      gamma chain has a COOH-terminal globular domain (gamma C, residues 151-411 of the
      gamma chain, 30 kDa) to which several integrin cell adhesion receptors (e.g.,
      platelet alpha(IIb)beta(3), endothelial alpha(v)beta(3), and leukocyte
      alpha(M)beta(2)) bind. Integrins play a critical role in signal transduction from
      fibrin(ogen). We found that gamma C and its truncation mutant (designated gamma
      C399tr), with a deletion of the COOH-terminal 12 residues, induced apoptosis of
      endothelial cells and blocked tube formation of endothelial cells. DLD-1 human
      colon cancer cells that secrete gamma C or gamma C399tr grew at similar levels in
      vitro but grew much slower in vivo than mock-transfected cells. The recombinant
      purified gamma C399tr fragment markedly suppressed tumor growth, development of
      intratumoral vasculature, and tumor metastasis in vivo in the highly metastatic
      Met-1 breast cancer model. The determinant responsible for binding to endothelial
      cells is cryptic in native fibrinogen but is exposed in gamma C and gamma C399tr.
      These results suggest that fibrinogen has a novel cryptic determinant, which can
      exert apoptosis-inducing activity on endothelial cells when exposed, and
      polypeptides containing this determinant have therapeutic potential.

PMID- 17018628
TI  - Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its
      importance for guiding combined antitumor therapy.
AB  - Emerging preclinical studies support the concept of a transient "normalization"
      of tumor vasculature during the early stage of antiangiogenic treatment, with
      possible beneficial effects on associated radiotherapy or chemotherapy. One key
      issue in this area of research is to determine whether this feature is common to
      all antiangiogenic drugs and whether the phenomenon occurs in all types of
      tumors. In the present study, we characterized the evolution of the tumor
      oxygenation (in transplantable liver tumor and FSAII tumor models) after
      administration of SU5416, an antagonist of the vascular endothelial growth factor
      receptor. SU5416 induced an early increase in tumor oxygenation [measured by
      electronic paramagnetic resonance (EPR)], which did not correlate with remodeling
      of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry)
      or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance
      imaging). Inhibition of mitochondrial respiration (measured by EPR) was
      responsible for this early reoxygenation. Consistent with these unique findings
      in the tumor microenvironment, we found that SU5416 potentiated tumor response to
      radiotherapy but not to chemotherapy. In addition to the fact that the
      characterization of the tumor oxygenation is essential to enable correct
      application of combined therapies, our results show that the long-term inhibition
      of oxygen consumption is a potential novel target in this class of compounds.

PMID- 17018629
TI  - Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and
      prostaglandin E2 production in human colon cancer cells.
AB  - Inhibition of prostaglandin E(2) (PGE(2)) and cyclooxygenase (COX)-2 by
      nonsteroidal anti-inflammatory drugs reduces the progression of colon cancer.
      Inhibition of aldose reductase (AR; EC. 1.1.1.21.) by sorbinil or by antisense
      ablation prevented fibroblast growth factor-induced and platelet-derived growth
      factor-induced up-regulation of PGE(2) synthesis in human colon cancer cells,
      Caco-2. AR besides reducing aldo-sugars efficiently reduces toxic lipid aldehydes
      and their conjugates with glutathione. Inhibition of AR prevented growth factor
      induced COX-2 activity, protein, and mRNA and significantly decreased activation
      of nuclear factor-kappaB and protein kinase C (PKC) and phosphorylation of PKC
      beta2 as well as progression of Caco-2 cell growth but had no effect on COX-1
      activity. Cell cycle analysis suggests that inhibition of AR prevents growth
      factor-induced proliferation of Caco-2 cells at S phase. Treatment of Caco-2
      cells with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal
      (HNE) or its glutathione-conjugate [glutathionyl-HNE (GS-HNE)] or AR-catalyzed
      product of GS-HNE, glutathionyl-1,4-dihydroxynonane (GS-DHN), resulted in
      increased COX-2 expression and PGE(2) production. Inhibition of AR prevented HNE-
      or GS-HNE-induced but not GS-DHN-induced up-regulation of COX-2 and PGE(2). More
      importantly, in vivo studies showed that administration of AR-small interfering
      RNA (siRNA), but not control siRNA, to nude mice bearing SW480 human colon
      adenocarcinoma cells completely arrested tumor progression. Collectively, these
      observations suggest that AR is an obligatory mediator of growth factor-induced
      up-regulation of COX-2, PGE(2), and growth of Caco-2 cells, indicating that
      inhibition of AR may be a novel therapeutic approach in preventing the
      progression of colon cancer.

PMID- 17018630
TI  - Pyridone 6, a pan-Janus-activated kinase inhibitor, induces growth inhibition of
      multiple myeloma cells.
AB  - Interleukin-6 (IL-6) and the subsequent Janus-activated kinase (JAK)-dependent
      signaling pathways play a critical role in the pathogenesis of multiple myeloma.
      Here, we compared the sensitivity and specificity of a novel pan-JAK inhibitor,
      tetracyclic pyridone 6 (P6), with that of AG490 in a panel of myeloma-derived
      cell lines. P6 induced growth arrest and subsequent apoptosis of the IL-6
      dependent hybridoma and myeloma-derived cell lines (B9 and INA-6) grown either in
      IL-6-containing medium or in the presence of bone marrow-derived stromal cells
      (BMSC) using much lower concentrations of drug and with significantly faster
      kinetics than AG490. Myeloma-derived cell lines, which either express
      constitutively activated JAK/signal transducers and activators of transcription
      (STAT) 3 (U266) or are IL-6 growth stimulated (KMS11), are partially growth
      inhibited by P6. However, P6 does not inhibit the growth of myeloma-derived cell
      lines lacking activated JAKs/STATs nor does it inhibit mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) kinase activity compared with
      AG490, which led to activation of ERK and induced robust apoptosis of all the
      examined cell lines. Finally, P6 inhibited the growth of primary myeloma patient
      samples grown in the presence of BMSCs. Thus, P6 is a more sensitive and specific
      inhibitor of JAK-STAT3 activity compared with AG490 and potently inhibited the
      growth of primary myeloma cells and myeloma-derived cell lines grown on BMSCs.

PMID- 17018631
TI  - Identification of an agent selectively targeting DPC4 (deleted in pancreatic
      cancer locus 4)-deficient pancreatic cancer cells.
AB  - One of the most common types of genetic alterations in cancer is the loss-of
      function mutations in tumor-suppressor genes. Such mutations are usually very
      specific to cancer cells and present attractive and unique opportunities for
      therapeutic interventions. However, for various reasons, antitumor agents that
      target loss-of-function mutations have not been readily identified. In this
      report, using the deleted in pancreatic cancer locus 4 (DPC4) gene in pancreatic
      cancer as an example, we show the feasibility of a novel screening strategy,
      which we have named Pharmacological Synthetic Lethal Screening, for the
      identification of agents that selectively target cancer cells with loss-of
      function mutations. We created DPC4 isogenic cell lines through the restoration
      of wild-type DPC4 in a pancreatic cancer cell line, BxPC-3, whose DPC4 gene was
      homozygously deleted. The isogenic cell lines were then used in the
      Pharmacological Synthetic Lethal Screening to evaluate compound libraries for
      antiproliferative activity and selectivity against DPC4 deficiency. After
      screening 19,590 compounds, we identified one lead compound, UA62001, which
      showed 4.6-fold selectivity against DPC4 deficiency in the DPC4 isogenic cell
      lines. UA62001 selectivity was also seen in another set of DPC4 isogenic cell
      lines generated by small interfering RNA knockdown. In addition, UA62001 was
      evaluated in commonly used pancreatic cancer cell lines. A fairly good
      correlation between DPC4 deficiency and UA62001 sensitivity was observed. Cell
      cycle analysis indicates that UA62001 arrests cells in S and G(2)-M phases. The
      results of microarray gene expression profiling and quantitative real-time
      reverse transcription-PCR suggest that cyclin B/CDC2 and minichromosome
      maintenance complexes might be the downstream cellular targets of UA62001.

PMID- 17018632
TI  - Identification of a chemical inhibitor of the oncogenic transcription factor
      forkhead box M1.
AB  - The oncogenic transcription factor forkhead box M1 (FoxM1) is overexpressed in a
      number of different carcinomas, whereas its expression is turned off in
      terminally differentiated cells. For this reason, FoxM1 is an attractive target
      for therapeutic intervention in cancer treatment. As a first step toward
      realizing this goal, in this study, using a high-throughput, cell-based assay
      system, we screened for and isolated the antibiotic thiazole compound Siomycin A
      as an inhibitor of FoxM1. Interestingly, we observed that Siomycin A was able to
      down-regulate the transcriptional activity as well as the protein and mRNA
      abundance of FoxM1. Consequently, we found that the downstream target genes of
      FoxM1, such as Cdc25B, Survivin, and CENPB, were repressed. Also, we observed
      that consistent with earlier reports of FoxM1 inhibition, Siomycin A was able to
      reduce anchorage-independent growth of cells in soft agar. Furthermore, we found
      that Siomycin A was able to induce apoptosis selectively in transformed but not
      normal cells of the same origin. Taken together, our data suggest that FoxM1
      inhibitor Siomycin A could represent a useful starting point for the development
      of anticancer therapeutics.

PMID- 17018633
TI  - Antitumor activity of an oncolytic adenovirus-delivered oncogene small
      interfering RNA.
AB  - Despite successes in animal models, cancer gene therapy with small interfering
      RNAs (siRNA) is hindered by the lack of an optimal delivery platform. We examined
      the applicability of the replication-competent, oncolytic adenovirus, ONYX-411,
      to deliver a mutant K-ras siRNA transgene to human cancer cells. Proof-of
      principle studies showed an additive tumor growth-inhibitory response through
      siRNA-mediated K-ras knockdown and ONYX-411-mediated cancer cell lysis. A novel
      construct, termed Internavec (for interfering RNA vector), was generated by
      cloning a K-ras(v12)-specific siRNA(ras-4) hairpin construct under the control of
      the human H1 promoter into the deleted E3b region of ONYX-411. Internavec
      acquired an increase in potency of approximately 10-fold in human cancer cells
      expressing the relevant K-ras(v12) mutation (H79, H441, and SW480), as defined by
      a reduction in the effective dose needed to achieve 50% growth inhibition
      (ED(50)). Internavec remained attenuated in nonmalignant epithelial cells. Daily
      intratumoral injections of Internavec (five daily injections of 1 x 10(8) plaque
      forming units) significantly reduced the growth of s.c. H79 pancreatic cancer
      xenografts in nu/nu mice by 85.5%, including complete growth suppression in three
      of five mice. Parental ONYX-411 or ONYX-411-siRNA(GFP) was markedly less
      effective (47.8% growth reduction, P = 0.03; and 44.1% growth reduction, P =
      0.03, respectively). siRNA(ras) transgene activity contributed to cell cycle
      blockage, increased apoptosis, and marked down-regulation of Ras signaling
      related gene expression (AKT2, GSK3 beta, E2F2, and MAP4K5). These findings
      indicate that Internavec can generate a two-pronged attack on tumor cells through
      oncogene knockdown and viral oncolysis, resulting in a significantly enhanced
      antitumor outcome.

PMID- 17018634
TI  - The differential staurosporine-mediated G1 arrest in normal versus tumor cells is
      dependent on the retinoblastoma protein.
AB  - Previously, we reported that breast cancer cells with retinoblastoma (pRb)
      pathway-defective checkpoints can be specifically targeted with chemotherapeutic
      agents, following staurosporine-mediated reversible growth inhibition in normal
      cells. Here we set out to determine if the kinetics of staurosporine-mediated
      growth inhibition is specifically targeted to the G(1) phase of cells, and if
      such G(1) arrest requires the activity of wild-type pRb. Normal human mammary
      epithelial and immortalized cells with intact pRb treated with low concentrations
      of staurosporine arrested in the G(1) phase of the cell cycle, whereas pRb
      defective cells showed no response. The duration of G(1) and transition from G(1)
      to S phase entry were modulated by staurosporine in Rb-intact cells. In pRb(+)
      cells, but not in Rb(-) cells, low concentrations of staurosporine also resulted
      in a significant decrease in cyclin-dependent kinase 4 (CDK4) expression and
      activity. To directly assess the role of pRb in staurosporine-mediated G(1)
      arrest, we subjected wild-type (Rb(+/+)) and pRb(-/-) mouse embryo fibroblasts
      (MEFs) to staurosporine treatments. Our results show that whereas Rb(+/+) MEFs
      were particularly sensitive to G(1) arrest mediated by staurosporine, pRb(-/-)
      cells were refractory to such treatment. Additionally, CDK4 expression was also
      inhibited in response to staurosporine only in Rb(+/+) MEFs. These results were
      recapitulated in breast cancer cells treated with siRNA to pRb to down-regulate
      the pRb expression. Collectively, our data suggest that treatment of cells with
      nanomolar concentrations of staurosporine resulted in down-regulation of CDK4,
      which ultimately leads to G(1) arrest in normal human mammary epithelial and
      immortalized cells with an intact pRb pathway, but not in pRb-null/defective
      cells.

PMID- 17018635
TI  - The tumor antigen repertoire identified in tumor-bearing neu transgenic mice
      predicts human tumor antigens.
AB  - FVB/N mice transgenic for nontransforming rat neu develop spontaneous breast
      cancers that are neu positive and estrogen receptor negative, mimicking
      premenopausal human breast cancer. These animals have been widely used as a model
      for immunobased therapies targeting HER-2/neu. In this study, we used serological
      analysis of recombinant cDNA expression libraries to characterize the antigenic
      repertoire of neu transgenic (neu-tg) mice and questioned the ability of this
      murine model to predict potential human tumor antigens. After screening 3 x 10(6)
      clones from 3 different cDNA libraries, 15 tumor antigens were identified,
      including cytokeratin 2-8, glutamyl-prolyl-tRNA synthetase, complement C3,
      galectin 8, and serine/threonine-rich protein kinase 1. Multiple proteins
      involved in the Rho/Rho-associated, coiled coil-containing protein kinase (Rock)
      signal transduction pathway were found to be immunogenic, including Rock1,
      Rho/Rac guanine nucleotide exchange factor 2, and schistosoma mansoni adult worm
      antigen preparation 70. All of the identified antigens are self-proteins that are
      expressed in normal tissues in addition to breast tumors and the majority of the
      antigens are intracellular proteins. More than half of the mouse tumor antigens
      have human homologues that have been reported previously as tumor antigens.
      Finally, the tumor-specific antibody immunity and marked immune cell infiltration
      that was observed in mice with spontaneous tumors were not observed in mice with
      transplanted tumors. Our results indicate that neu-tg mice bearing spontaneous
      tumors develop humoral immunity to their tumors similar to cancer patients and
      that tumor antigens identified in transgenic mouse may predict immunogenic human
      homologues.

PMID- 17018636
TI  - Involvement of mitochondrial and Akt signaling pathways in augmented apoptosis
      induced by a combination of low doses of celecoxib and N-(4-hydroxyphenyl)
      retinamide in premalignant human bronchial epithelial cells.
AB  - Celecoxib is being evaluated as a chemopreventive agent. However, its mechanism
      of action is not clear because high doses were used for in vitro studies to
      obtain antitumor effects. We found that celecoxib inhibited the growth of
      premalignant and malignant human bronchial epithelial cells with IC(50) values
      between 8.9 and 32.7 micromol/L, irrespective of cyclooxygenase-2 (COX-2)
      expression. Normal human bronchial epithelial cells were less sensitive to
      celecoxib. Because these concentrations were higher than those attainable in vivo
      (<or=5.6 micromol/L), we surmised that combining celecoxib with the synthetic
      retinoid N-(4-hydroxyphenyl) retinamide (4HPR) might improve its efficacy.
      Treatment of premalignant lung cell lines with combinations of clinically
      relevant concentrations of celecoxib (<or=5 micromol/L) and 4HPR (<or=0.25
      micromol/L) resulted in greater growth inhibition, apoptosis induction, and
      suppression of colony formation than did either agent alone. This combination
      also decreased the levels of Bcl-2, induced the release of mitochondrial
      cytochrome c, activated caspase-9 and caspase-3, and induced cleavage of poly(ADP
      ribose)polymerase at concentrations at which each agent alone showed no or
      minimal effects. Furthermore, combinations of celecoxib and 4HPR suppressed the
      phosphorylation levels of serine/threonine kinase Akt and its substrate glycogen
      synthase kinase-3beta more effectively than the single agents did. Accordingly,
      overexpression of constitutively active Akt protected bronchial epithelial cells
      from undergoing apoptosis after incubation with both celecoxib and 4HPR. These
      findings indicate that activation of the mitochondrial apoptosis pathway and
      suppression of the Akt survival pathway mediate the augmented apoptosis and
      suggest that this combination may be useful for lung cancer chemoprevention.

PMID- 17018637
TI  - Common genetic variants in proinflammatory and other immunoregulatory genes and
      risk for non-Hodgkin lymphoma.
AB  - Profound disruption of immune function is an established risk factor for non
      Hodgkin lymphoma. We report here a large-scale evaluation of common genetic
      variants in immune genes and their role in lymphoma. We genotyped 57 single
      nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non
      Hodgkin lymphoma cases and 982 population-based controls from a US multicenter
      study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for
      the association between individual SNP and haplotypes with non-Hodgkin lymphoma
      overall and five well-defined subtypes. A haplotype comprising SNPs in two
      proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha
      (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin
      lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for
      diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional
      nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A;
      rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes
      were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10
      1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma
      subtypes, the association with FCGR2A was pronounced for follicular and small
      lymphocytic lymphomas. In conclusion, common variants in genes influencing
      proinflammatory and innate immune responses were associated with non-Hodgkin
      lymphoma risk overall and their effects could vary by subtype. Our results
      require replication but potentially provide important clues for investigating
      common genetic variants as susceptibility factors and in disease outcomes,
      treatment responses, and immunotherapy targets.

PMID- 17018638
TI  - Comprehensive assessment of genetic variation of catechol-O-methyltransferase and
      breast cancer risk.
AB  - Because catechol-O-methyltransferase (COMT) catalyzes the addition of methyl
      groups to stabilize catechol estrogens that may induce DNA damage, genetic
      variants could influence breast cancer risk. To comprehensively characterize
      genetic variation in this gene, we selected haplotype-tagging single nucleotide
      polymorphisms (htSNP) in COMT. A total of 11 htSNPs (including COMT Val(158)Met)
      were selected based on the resequencing and dense genotyping approach of the
      Breast and Prostate Cancer Cohort Consortium. htSNPs were genotyped in a
      population-based, case-control study in Poland (1,995 cases and 2,296 controls).
      Individual SNPs were not significantly associated with risk. Haplotypes were
      estimated using the expectation-maximization algorithm. Overall differences in
      the haplotype distribution between cases and controls were assessed using a
      global score test. The TGAG haplotype (frequent in 4.3% of controls), in a
      linkage disequilibrium (LD) block that included the 3' untranslated region (UTR)
      of COMT, was associated with breast cancer risk (odds ratio, 1.29; 95% confidence
      interval, 1.06-1.58) compared with the most common haplotype TGAA; however, the
      global test for haplotype associations was not significant (P = 0.09). Haplotypes
      in another LD block, which included COMT Val(158)Met, were not associated with
      breast cancer risk (global P = 0.76). Haplotype-breast cancer risk associations
      were not significantly modified by hormonally related risk factors, family
      history of breast cancer, or tumor characteristics. In summary, our data does not
      support a substantial overall association between COMT haplotypes and breast
      cancer. The suggestion of increased risk associated with a haplotype in the 3'
      UTR of COMT needs to be confirmed in independent study populations.

PMID- 17018640
TI  - CD99-positive "Ewing's sarcoma" from mouse-bone marrow-derived mesenchymal
      progenitor cells?

PMID- 17018641
TI  - Models for spontaneous metastasis.

PMID- 17018642
TI  - Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription
      factor by MyD88 in Toll-like receptor-dependent gene induction program.
AB  - The recognition of microbial components by Toll-like receptors (TLRs) initiates
      signal transduction pathways, which trigger the expression of a series of target
      genes. It has been reported that TLR signaling is enhanced by cytokines such as
      IFN-gamma, but the mechanisms underlying this enhancement remain unclear. The
      MyD88 adaptor, which is essential for signaling by many TLRs, recruits members of
      the IFN regulatory factor (IRF) family of transcription factors, such as IRF5 and
      IRF7, to evoke the activation of TLR target genes. In this study we demonstrate
      that IRF1, which is induced by IFN-gamma, also interacts with and is activated by
      MyD88 upon TLR activation. We provide evidence that MyD88-associated IRF1
      migrates into the nucleus more efficiently than non-MyD88-associated IRF1 and
      that this IRF1 selectively participates in the TLR-dependent gene induction
      program. The critical role of MyD88-dependent "IRF1 licensing" is underscored by
      the observation that the induction of a specific gene subset downstream of the
      TLR-MyD88 pathway, such as IFN-beta, inducible NO synthase, and IL-12p35, are
      impaired in Irf1-deficient cells. Thus, our present study places IRF1 as an
      additional member participating in MyD88 signaling and provides a mechanistic
      insight into the enhancement of the TLR-dependent gene induction program by IFN
      gamma.

PMID- 17018644
TI  - A retrovirus-based protein complementation assay screen reveals functional AKT1
      binding partners.
AB  - We developed a retrovirus-based protein-fragment complementation assay (RePCA)
      screen to identify protein-protein interactions in mammalian cells. In RePCA,
      bait protein is fused to one fragment of a rationally dissected fluorescent
      protein, such as GFP, intensely fluorescent protein, or red fluorescent protein.
      The second, complementary fragment of the fluorescent protein is fused to an
      endogenous protein by in-frame exon traps in the enhanced retroviral mutagen
      vector. An interaction between bait and host protein (prey) places the two parts
      of the fluorescent molecule in proximity, resulting in reconstitution of
      fluorescence. By using RePCA, we identified a series of 24 potential interaction
      partners or substrates of the serine/threonine protein kinase AKT1. We confirm
      that alpha-actinin 4 (ACTN4) interacts physically and functionally with AKT1.
      siRNA-mediated ACTN4 silencing down-regulates AKT phosphorylation, blocks AKT
      translocation to the membrane, increases p27(Kip1) levels, and inhibits cell
      proliferation. Thus, ACTN4 is a critical regulator of AKT1 localization and
      function.

PMID- 17018645
TI  - The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2
      induction through both NADP(H) oxidase and PKC epsilon inhibition.
AB  - A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid
      (DHA)] has been associated with systemic antiinflammatory effects and
      cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the
      overproduction of prostaglandins (PG) at inflammatory sites, and its expression
      is increased in atheroma. We studied the effects of DHA on COX-2 expression and
      activity in human saphenous vein endothelial cells challenged with
      proinflammatory stimuli. A>or=24-h exposure to DHA reduced COX-2 expression and
      activity induced by IL-1, without affecting COX-1 expression. DHA effect depended
      on the NF-kappaB-binding site in the COX-2 promoter. EMSAs confirmed that DHA
      attenuated NF-kappaB activation. Because MAPK, PKC, and NAD(P)H oxidase all
      participate in IL-1-mediated COX-2 expression, we also tested whether these
      enzymes were involved in DHA effects. Western blots showed that DHA blocked
      nuclear p65 NF-kappaB subunit translocation by decreasing cytokine-stimulated
      reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase
      and PKCepsilon activities. Finally, to address the question whether DHA itself or
      DHA-derived products were responsible for these effects, we inhibited the most
      important enzymes involved in polyunsaturated fatty acid metabolism, showing that
      15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a
      mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of
      DHA.

PMID- 17018646
TI  - Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: oxidation of
      thioredoxin and caspase-3 activation.
AB  - Paraquat, N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine, and rotenone have been
      shown to reproduce several features of Parkinson's disease in animal and cell
      culture models. Although these chemicals are known to perturb dopamine
      homeostasis and induce dopaminergic cell death, their molecular mechanisms of
      action are not well defined. We have previously shown that paraquat does not
      require functional dopamine transporter and does not inhibit mitochondrial
      complex I in order to mediate its toxic action (Richardson et al., 2005). In this
      study, we show that paraquat specifically oxidized the cytosolic form of
      thioredoxin and activated Jun N-terminal kinase (JNK), followed by caspase-3
      activation. Conversely, 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone
      oxidized the mitochondrial form of thioredoxin but did not activate JNK-mitogen
      activated protein kinase and caspase-3. Loading cells with exogenous dopamine did
      not exacerbate the toxicity of any of these compounds. These data suggest that
      oxidative modification of cytosolic proteins is critical to paraquat toxicity,
      while oxidation of mitochondrial proteins is important for MPP(+) and rotenone
      toxicity. In addition, intracellular dopamine does not seem to exacerbate the
      toxicity of these dopaminergic neurotoxicants in this model.

PMID- 17018647
TI  - Age-related brain cholinesterase inhibition kinetics following in vitro
      incubation with chlorpyrifos-oxon and diazinon-oxon.
AB  - Chlorpyrifos and diazinon are two commonly used organophosphorus insecticides
      (OPs), and their primary mechanism of action involves the inhibition of
      acetylcholinesterase by their metabolites chlorpyrifos-oxon (CPO) and diazinon
      oxon (DZO), respectively. The study objectives were to assess the in vitro age
      related inhibition kinetics of neonatal rat brain cholinesterase (ChE) for CPO
      and DZO by estimating the bimolecular inhibitory rate constant (k(i)) values.
      Brain ChE inhibition and k(i) values following CPO and DZO incubation with
      neonatal Sprague-Dawley rat brain homogenates were determined at postnatal day
      (PND) 5, 12, and 17 and compared with the corresponding inhibition and k(i)
      values obtained in the adult rat. A modified Ellman method was utilized for
      measuring the ChE activity. CPO caused a greater ChE inhibition than DZO as
      evidenced from the estimated k(i) values of both compounds. Neonatal brain ChE
      inhibition kinetics exhibited a marked age-related sensitivity to CPO, with the
      order of ChE inhibition being PND 5 > PND 7 > PND 17 with k(i) values of 0.95,
      0.50, and 0.22 nM(-1)hr(-1), respectively. In contrast, DZO ChE inhibition was
      not age related in the neonatal brain, and the estimated k(i) value at all PND
      ages was 0.02 nM(-1)hr(-1). These results demonstrated an age- and OP-selective
      inhibition of rat brain ChE, which may be critically important in understanding
      the potential sensitivity of juveniles to specific OPs exposures.

PMID- 17018648
TI  - Disruption of testosterone homeostasis as a mode of action for the reproductive
      toxicity of triazole fungicides in the male rat.
AB  - Triazole fungicides associated with a range of reported male reproductive effects
      in experimental animals were selected to assess potential toxic modes of action.
      Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole
      (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from
      gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on
      PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0,
      body and organ weights, serum hormone levels, age at preputial separation (PPS),
      sperm morphology and motility, and fertility and fecundity. AGD was increased by
      the high dose of all three triazoles, indicating hypervirilization. Triadimefon
      delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights
      were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular
      hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92
      from all three high-dose triazole treatments. Relative pituitary weights were
      decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute
      testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil
      and triadimefon, and at PND50 by propiconazole and triadimefon treatment.
      Relative ventral prostate weights were increased at PND92 by myclobutanil and
      triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon
      and at PND92/99 by all three triazole treatments. Insemination and fertility were
      impaired by myclobutanil and triadimefon treatment. In addition to the
      reproductive system effects, total serum thyroxine levels were decreased at PND92
      by high-dose triadimefon. These reproductive effects are consistent with the
      disruption of testosterone homeostasis as a key event in the mode of action for
      triazole-induced reproductive toxicity.

PMID- 17018649
TI  - Maternally inherited diabetes and deafness in a North American kindred: tips for
      making the diagnosis and review of unique management issues.
AB  - CONTEXT: Mutations in mitochondrial DNA are rare etiologies of adult-onset
      diabetes mellitus (DM) that merit identification to 1) prevent iatrogenic lactic
      acidosis, 2) prompt appropriate screening of affected patients and their
      families, 3) provide genetic counseling, and 4) provide an opportunity to
      investigate strategies for preventing diabetes. OBJECTIVE: The objective of this
      study is to raise awareness of this rare form of adult-onset nonobese DM so that
      these patients are identified and provided with appropriate care. PATIENTS: We
      describe a kindred in which four of seven siblings have adult-onset DM and
      sensorineural hearing loss with a confirmed genetic mutation at position 3243 in
      the tRNA. Two other siblings in this kindred demonstrate different phenotypes of
      mitochondrial disease. INTERVENTION: The proband was treated with coenzyme Q10
      for 1 yr. OUTCOME MEASURES: Outcome measures included stress thallium exercise
      testing and audiometry testing. RESULTS: After 1 yr of treatment of with coenzyme
      Q10, repeat stress thallium testing demonstrated improvement in the exercise
      tolerance of the proband from 7-12 min. Audiometry testing did not demonstrate a
      change in the rate of hearing decline. CONCLUSION: Maternally inherited diabetes
      and deafness is a rare cause of DM that is important to diagnose because of the
      unique management issues and associated comorbidities. This work highlights clues
      to the identification of this rare monogenic form of adult- onset diabetes.

PMID- 17018650
TI  - Androgen therapy in women: an Endocrine Society Clinical Practice guideline.
AB  - OBJECTIVE: The objective was to provide guidelines for the therapeutic use of
      androgens in women. PARTICIPANTS: The Task Force was composed of a chair,
      selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society,
      six additional experts, a methodologist, and a medical writer. The Task Force
      received no corporate funding or remuneration. EVIDENCE: The Task Force used
      systematic reviews of available evidence to inform its key recommendations. The
      Task Force used consistent language and graphical descriptions of both the
      strength of recommendation and the quality of evidence, using the recommendations
      of the Grading of Recommendations, Assessment, Development, and Evaluation
      (GRADE) group. The strength of a recommendation is indicated by the number 1
      (strong recommendation, associated with the phrase "we recommend") or 2 (weak
      recommendation, associated with the phrase "we suggest"). The quality of the
      evidence is indicated by cross-filled circles, such that [1 cross-filled circle,
      3 empty circles] denotes very-low-quality evidence, [2 cross-filled circles, 2
      empty circles] low quality, [3 cross-filled circles, 1 empty circle] moderate
      quality, and [4 cross-filled circles] high quality. Each recommendation is
      followed by a description of the evidence. CONSENSUS PROCESS: Consensus was
      guided by systematic reviews of evidence and discussions during one group
      meeting, several conference calls, and e-mail communications. The drafts prepared
      by the task force with the help of a medical writer were reviewed successively by
      The Endocrine Society's CGS, Clinical Affairs Committee (CAC), and Executive
      Committee. The version approved by the CGS and CAC was placed on The Endocrine
      Society's web site for comments by members. At each stage of review, the Task
      Force received written comments and incorporated needed changes. CONCLUSIONS: We
      recommend against making a diagnosis of androgen deficiency in women at present
      because of the lack of a well-defined clinical syndrome and normative data on
      total or free testosterone levels across the lifespan that can be used to define
      the disorder. Although there is evidence for short-term efficacy of testosterone
      in selected populations, such as surgically menopausal women, we recommend
      against the generalized use of testosterone by women because the indications are
      inadequate and evidence of safety in long-term studies is lacking. A review of
      the data currently available is presented, and areas of future research are
      outlined. To formulate clinical guidelines for use of testosterone in women,
      additional information will be necessary. This includes defining conditions that,
      when not treated with androgens, have adverse health consequences to women;
      defining clinical and laboratory parameters that distinguish those with these
      conditions; and assessing the efficacy and long-term safety of androgen
      administration on outcomes that are important to women diagnosed with these
      conditions. This necessary clinical research cannot occur until the biological,
      physiological, and psychological underpinnings of the role of androgens in women
      and candidate disorders are further elucidated.

PMID- 17018643
TI  - A molecular neuroethological approach for identifying and characterizing a
      cascade of behaviorally regulated genes.
AB  - Songbirds have one of the most accessible neural systems for the study of brain
      mechanisms of behavior. However, neuroethological studies in songbirds have been
      limited by the lack of high-throughput molecular resources and gene-manipulation
      tools. To overcome these limitations, we constructed 21 regular, normalized, and
      subtracted full-length cDNA libraries from brains of zebra finches in 57
      developmental and behavioral conditions in an attempt to clone as much of the
      brain transcriptome as possible. From these libraries, approximately 14,000
      transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs,
      we created a hierarchically organized transcriptome database and a large-scale
      songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes
      that are regulated in forebrain vocal nuclei by singing behavior. These genes
      clustered into four anatomical and six temporal expression patterns. Their
      functions spanned a large range of cellular and molecular categories, from signal
      transduction, trafficking, and structural, to synaptically released molecules.
      With the full-length cDNAs and a lentiviral vector system, we were able to
      overexpress, in vocal nuclei, proteins of representative singing-regulated genes
      in the absence of singing. This publicly accessible resource
      http://songbirdtranscriptome.net can now be used to study molecular
      neuroethological mechanisms of behavior.

PMID- 17018651
TI  - Growth hormone treatment improves growth and clinical status in prepubertal
      children with cystic fibrosis: results of a multicenter randomized controlled
      trial.
AB  - CONTEXT: This multicenter, randomized, controlled, crossover trial of prepubertal
      children with cystic fibrosis (CF) tests the hypotheses that recombinant human GH
      (rhGH) treatment 1) improves height, weight, lean mass, and bone content
      irrespective of baseline measures; 2) improves clinical status and quality of
      life; and 3) has continued effect after cessation after 1 yr of treatment.
      METHODS: Sixty-one prepubertal subjects (<or=25th percentile for height and
      weight) were randomized into two groups: daily rhGH treatment or no treatment
      groups for 1 yr. In yr 2, treatments were crossed over. Outcome measures included
      serial standardized height and weight, number of hospitalizations and antibiotic
      courses, random blood glucose levels, lean mass, bone mineral content, pulmonary
      function, nutritional intake, and CF quality of life questionnaires. RESULTS:
      Groups were similar at baseline and prepubertal during the entire study. After 1
      yr, GH showed significantly greater gain in height, weight, lean mass, and bone
      mineral content. Gain in height was similar regardless of baseline. There were
      fewer hospitalizations in the rhGH-treated group and improvement in CF quality of
      life questionnaires measures of weight and body image. There was no difference in
      pulmonary function between groups. Results were similar in those treated with
      rhGH the second year. After cessation of rhGH treatment, there was sustained
      effect for increased height and weight velocity, as well as accrual of bone
      mineral. CONCLUSION: rhGH therapy improves height and weight, decreases the
      number of hospitalizations, and improves quality of life in prepubertal children
      with CF. These effects are sustained after rhGH is discontinued.

PMID- 17018652
TI  - Adiponectin concentration in umbilical cord serum is positively associated with
      the weight ratio of fetus to placenta.
AB  - CONTEXT: Adiponectin (APN) concentration in umbilical cord serum is higher than
      that in adult serum. Except for the positive association between birth weight and
      cord APN concentration, little is known about the pathophysiological function of
      APN in fetal development. OBJECTIVE: The objective of this study was to evaluate
      the relationship of cord serum APN and IGF-I concentrations with the development
      of the fetoplacental unit. DESIGN AND METHODS: Umbilical cord serum APN and IGF-I
      concentrations were measured in term singleton deliveries (n = 94). The
      association of cord APN and IGF-I concentrations was evaluated in relation to
      fetal weight, placental weight, and fetoplacental (F/P) weight ratio. RESULTS:
      Mean concentrations and sd of APN and IGF-I were 36.1 +/- 14.0 microg/ml and 58.6
      +/- 27.0 ng/ml, respectively. Cord APN concentration was positively associated
      with F/P weight ratio (r = 0.375, P < 0.001) as well as fetal weight (r = 0.389,
      P < 0.001) but not placental weight. Cord IGF-I concentration was positively
      associated with fetal weight (r = 0.405, P < 0.001) and placental weight (r =
      0.400, P < 0.001) but not F/P weight ratio. In multiregression analysis, only APN
      concentration resulted in a significant determinant of F/P weight ratio among
      variables (beta = 0.376, P < 0.001). CONCLUSIONS: In cord hyperadiponectinemia,
      fetuses tend to be disproportionately larger for their placental weight and vice
      versa in cord hypoadiponectinemia. APN is shown to be the first biomarker
      positively associated with F/P weight ratio.

PMID- 17018653
TI  - Aryl hydrocarbon receptor interacting protein variants in sporadic pituitary
      adenomas.
AB  - CONTEXT: Proximal pathogenesis of pituitary tumors remains largely unclear.
      Recently, three heterozygous germline mutations were reported in the aryl
      hydrocarbon receptor interacting protein (AIP) gene in Finnish and Italian
      families with pituitary tumor predisposition and in Finnish patients harboring
      sporadic pituitary tumors. OBJECTIVE: The objectives of this study were to
      examine the frequency of the three AIP germline mutations in U.S. patients
      harboring sporadic pituitary tumors and to correlate clinical features of
      pituitary tumors with these mutations, if they exist in these patients. DESIGN:
      Genomic DNA was extracted from lymphoblastoid cell lines established from
      patients with sporadic pituitary tumors. Three segments of the AIP gene that
      contain the reported mutation sites for Q14X, IVS3-1G>A, and R304X were amplified
      by PCR and sequenced. SETTING: The study was conducted in a private nonprofit
      academic medical center. PATIENTS: The subjects were 66 consecutive patients
      (including 52 with acromegaly or prolactinoma) participating in a pituitary tumor
      database who consented to genetic study. MAIN OUTCOME MEASURE(S): The main
      outcome measure was the prevalence of these specific germline mutations in
      affected individuals. RESULTS: AIP mutations were not detected in the 66
      patients. A synonymous polymorphism was found in a single patient with
      acromegaly. CONCLUSIONS: The three specific AIP germline mutations do not play an
      important role in pathogenesis of sporadic pituitary tumors in U.S. patients.

PMID- 17018654
TI  - Pulsatile secretion of growth hormone (GH) persists during continuous stimulation
      by CJC-1295, a long-acting GH-releasing hormone analog.
AB  - CONTEXT: Pulsatile GH secretion is considered important for many of the hormone's
      physiological effects. Short-term GHRH infusions enhance GH pulsatility and
      increase IGF-I, but the short GHRH half-life limits its therapeutic use. A
      synthetic GHRH analog (CJC-1295) that binds permanently to endogenous albumin
      after injection (half-life = 8 d) stimulates GH and IGF-I secretion in several
      animal species and in normal human subjects and enhances growth in rats.
      OBJECTIVE: Our objective was to assess GH pulsatility after a single injection of
      CJC-1295 and determine which GH secretion parameters correlated to the increase
      in IGF-I production. METHODS: GH pulsatility was assessed by 20-min blood
      sampling during an overnight 12-h period in healthy 20- to 40-yr-old men before
      and 1 wk after injection of either 60 or 90 microg/kg CJC-1295. RESULTS: GH
      secretion was increased after CJC-1295 administration with preserved pulsatility.
      The frequency and magnitude of GH secretory pulses were unaltered. However, basal
      (trough) GH levels were markedly increased (7.5-fold; P < 0.0001) and contributed
      to an overall increase in GH secretion (mean GH levels, 46%; P < 0.01) and IGF-I
      levels (45%; P < 0.001). No significant differences were observed between the
      responses to the two drug doses. The IGF-I increases did not correlate with any
      parameters of GH secretion. CONCLUSIONS: CJC-1295 increased trough and mean GH
      secretion and IGF-I production with preserved GH pulsatility. The marked
      enhancement of trough GH levels by continuous GHRH stimulation implicates the
      importance of this effect on increasing IGF-I. Long-acting GHRH preparations may
      have clinical utility in patients with intact pituitary GH secretory capability.

PMID- 17018655
TI  - Regulation of A Disintegrin And Metalloproteinase with ThromboSpondin repeats-1
      expression in human endometrial stromal cells by gonadal steroids involves
      progestins, androgens, and estrogens.
AB  - CONTEXT: Gonadal steroids are key regulators of the extracellular matrix
      remodeling events that occur in the human endometrium during each menstrual
      cycle. The spatiotemporal expression of A Disintegrin And Metalloproteinase with
      ThromboSpondin repeats (ADAMTS)-1 in human endometrial stroma in vivo suggests
      that this novel metalloproteinase may contribute to this tightly regulated
      developmental process. OBJECTIVE: The objective of the study was to determine
      whether progesterone (P4), 17beta-estradiol (E2), or the nonaromatizable androgen
      dihydrotestosterone (DHT), alone or in combination, is capable of regulating
      ADAMTS-1 mRNA and protein levels in human endometrial stromal cells in a
      concentration- and time-dependent manner. DESIGN: A real-time quantitative PCR
      strategy and Western blotting were used to examine ADAMTS-1 mRNA and protein
      expression levels in primary cultures of human endometrial stromal cells.
      RESULTS: P4 and DHT but not E2 increased the levels of the ADAMTS-1 mRNA
      transcript and protein species (110 kDa) present in endometrial stromal cells in
      vitro in a concentration- and time-dependent manner. A combination of P4 and DHT
      resulted in an additional increase in stromal ADAMTS-1 expression, whereas E2
      attenuated the regulatory effects of P4 and DHT in a concentration-dependent
      manner. The antisteroidal compounds, mifepristone (RU486) and hydroxyflutamide,
      were also found to inhibit specifically the P4- and DHT-mediated increase in
      ADAMTS-1 mRNA and protein expression levels in these primary cell cultures in a
      concentration-dependent manner, respectively. CONCLUSIONS: These studies
      demonstrate that progestins, androgens, and estrogens, alone and in combination,
      have distinct regulatory effects on ADAMTS-1 mRNA and protein expression levels
      in human endometrial stromal cells in vitro.

PMID- 17018657
TI  - Exercise-induced improvement in vasodilatory function accompanies increased
      insulin sensitivity in obesity and type 2 diabetes mellitus.
AB  - OBJECTIVE: The present study was undertaken to determine whether improved
      vasodilatory function accompanies increased insulin sensitivity in overweight,
      insulin-resistant subjects (OW) and type 2 diabetic patients (T2DM) who
      participated in an 8-wk exercise training regimen. DESIGN: Before and after
      training, subjects had euglycemic clamps to determine insulin sensitivity.
      Brachial artery catheterization was done on another occasion for measurement of
      vasodilatory function. A lean, healthy, untrained group was studied as
      nonexercised controls. RESULTS: Training increased oxygen consumption (VO2) peak
      [OW, 29 +/- 1 to 37 +/- 4 ml/kg fat-free mass (FFM).min; T2DM, 33 +/- 2 to 43 +/-
      3 ml/kg FFM.min; P < 0.05] and improved insulin-stimulated glucose disposal (OW,
      6.5 +/- 0.5 to 7.2 +/- 0.4 mg/kg FFM.min; T2DM, 3.8 +/- 0.3 to 4.2 +/- 0.3 mg/kg
      FFM.min; P < 0.05) in insulin resistance. OW and T2DM, before training, had
      decreased acetylcholine chloride (ACh)- and sodium nitroprusside-mediated
      vasodilation and decreased reactive hyperemia compared with lean controls.
      Training increased the vasodilatory response to ACh [OW (30 microg ACh/min), 12.2
      +/- 3.4 to 19 +/- 4.2 ml/100 g.min; T2DM (30 microg ACh/min), 10.1 +/- 1.5 to
      14.2 +/- 2.1 ml/100 g.min; P < 0.05] in both groups without affecting
      nitroprusside response. CONCLUSION: Because vasodilatory dysfunction has been
      postulated to contribute to insulin resistance, the exercise-induced improvement
      in vasodilatory function may signify changes in the endothelium that could
      contribute to the improvement in insulin sensitivity observed after aerobic
      exercise training.

PMID- 17018656
TI  - A randomized controlled study of effects of dietary magnesium oxide
      supplementation on bone mineral content in healthy girls.
AB  - CONTEXT: The role of magnesium (Mg) as a determinant of bone mass has not been
      extensively explored. Limited studies suggest that dietary Mg intake and bone
      mineral density are correlated in adults, but no data from interventional studies
      in children and adolescents are available. OBJECTIVE: We sought to determine
      whether Mg supplementation in periadolescent girls enhances accrual of bone mass.
      DESIGN: We carried out a prospective, placebo-controlled, randomized, one-year
      double-blind trial of Mg supplementation. SETTING: The study was conducted in the
      Clinical Research Centers at Yale University School of Medicine. PATIENTS OR
      OTHER PARTICIPANTS: Healthy 8- to 14-yr-old Caucasian girls were recruited from
      community pediatricians' offices. Dietary diaries from over 120 volunteers were
      analyzed, and those with dietary Mg intake of less than 220 mg/d were invited to
      participate in the intervention. INTERVENTION: Magnesium (300 mg elemental Mg per
      day in two divided doses) or placebo was given orally for 12 months. MAIN OUTCOME
      MEASURE: The primary outcome measure was interval change in bone mineral content
      (BMC) of the total hip, femoral neck, Ward's area, and lumbar spine (L1-L4) after
      12 months of Mg supplementation. RESULTS: Significantly increased accrual (P =
      0.05) in integrated hip BMC occurred in the Mg-supplemented vs. placebo group.
      Trends for a positive Mg effect were evident in the pre- and early puberty and in
      mid-late puberty. Lumbar spinal BMC accrual was slightly (but not significantly)
      greater in the Mg-treated group. Compliance was excellent; 73% of capsules were
      ingested as inferred by pill counts. Serum mineral levels, calciotropic hormones,
      and bone markers were similar between groups. CONCLUSIONS: Oral Mg oxide capsules
      are safe and well tolerated. A positive effect of Mg supplementation on
      integrated hip BMC was evident in this small cohort.

PMID- 17018658
TI  - Association of interleukin-8 with hot flashes in premenopausal, perimenopausal,
      and postmenopausal women and bilateral oophorectomized women.
AB  - OBJECTIVE: The purpose of this study was to identify serum cytokine
      concentrations in premenopausal, perimenopausal, and postmenopausal women and
      bilateral oophorectomized women with hot flashes. METHODS: Serum concentrations
      of 17 cytokines were simultaneously measured using a multiplexed human cytokine
      assay in 129 premenopausal, perimenopausal, and postmenopausal women and 50
      bilateral oophorectomized women. RESULTS: Serum IL-8 concentrations in midlife
      women and bilateral oophorectomized women with severe hot flashes were
      significantly higher than the concentrations in women without hot flashes and
      women with mild and moderate hot flashes. Serum macrophage inflammatory protein
      1beta concentration in women with severe hot flashes was significantly higher
      than those in women without hot flashes and women with mild and moderate hot
      flashes. CONCLUSION: Serum IL-8 concentrations in premenopausal, perimenopausal,
      and postmenopausal women and bilateral oophorectomized women with hot flashes
      were significantly higher than those in women without hot flashes. IL-8 may be
      associated with peripheral vasodilation in women with hot flashes.

PMID- 17018659
TI  - A common polymorphism in the mineralocorticoid receptor modulates stress
      responsiveness.
AB  - CONTEXT: Mineralocorticoid receptors (MR) mediate the action of aldosterone on
      sodium resorption in kidney tubular cells, but in brain they respond to the
      glucocorticoid cortisol in stress regulation and cognitive processes. OBJECTIVE:
      The objective of the study was to investigate the role of the MR gene variant
      I180V in the neuroendocrine response to a psychosocial stressor and in
      electrolyte regulation. DESIGN: Associations between the MRI180V and outcome
      variables in a healthy cohort subjected to psychosocial challenge (Trier Social
      Stress Test) and in a mild hypertensive cohort exposed to acute salt loading
      (Weinberger's test) were investigated. In vitro transactivational assays were
      applied to compare the effects of cortisol and aldosterone on the MRI180V.
      RESULTS: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma
      cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social
      Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the
      Weinberger's test, no association was found with urinary sodium excretion, plasma
      aldosterone, and plasma renin activity or with changes in blood pressure,
      aldosterone, and renin responses. In vitro testing of the MR180V allele revealed
      a mild loss of function using cortisol as a ligand, compared with the MR180I
      allele. Significantly higher doses of cortisol were needed for half-maximal
      induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor
      virus (P < 0.02) promoters, whereas maximal induction was not different. These
      differences were not observed using aldosterone as a ligand. CONCLUSION: The
      findings reveal that cortisol and heart rate responses to a psychosocial stressor
      are enhanced in carriers of the MR180V variant.

PMID- 17018660
TI  - Primary hyperparathyroidism and the presence of kidney stones are associated with
      different haplotypes of the calcium-sensing receptor.
AB  - INTRODUCTION: Three single-nucleotide polymorphisms in the calcium-sensing
      receptor gene (CASR) encoding the missense substitutions A986S, R990G, and Q1011E
      have been associated with normal variation in extracellular calcium homeostasis,
      both individually and in haplotype combination. The aim of this study was to
      examine haplotype associations in primary hyperparathyroidism (PHPT). PATIENTS
      AND METHODS: Patients with sporadic PHPT (n = 237) were recruited from endocrine
      clinics and healthy controls (n = 433) from a blood donor clinic, and levels of
      serum calcium, albumin, and PTH were measured. In PHPT patients, urinary
      calcium/creatinine clearances and bone mineral density at spine and femoral neck
      were measured and the presence of kidney stones and vertebral fractures
      identified. The CASR single-nucleotide polymorphisms were haplotyped by allele
      specific sequencing. RESULTS: Four haplotypes (ARQ, SRQ, AGQ, and ARE) of eight
      were observed, in keeping with significant linkage disequilibrium, but haplotype
      frequencies did not show significant Hardy-Weinberg disequilibrium. The SRQ
      haplotype was more common in PHPT (125 of 474 alleles) than in controls (170 of
      866 alleles, P = 0.006) and showed a significant (P = 0.006) gene-dosage effect.
      There was no significant association between haplotype and bone mineral density
      or fractures, but association with kidney stones was significant (P = 0.0007). In
      the stone-forming subgroup, the SRQ haplotype was underrepresented and AGQ
      overrepresented. Patients bearing the AGQ haplotype had an odds ratio of 3.8 (95%
      confidence interval, 1.30-11.3) for presentation with renal stones compared with
      the rest. CONCLUSION: Our data indicate that the CASR SRQ haplotype is
      significantly associated with PHPT in our population. Within the PHPT patient
      population, the AGQ haplotype is significantly associated with kidney stones.

PMID- 17018661
TI  - Risk of thyroid cancer after childhood exposure to ionizing radiation for tinea
      capitis.
AB  - BACKGROUND: The thyroid gland is known to be sensitive to the carcinogenic effect
      of ionizing radiation, especially in children. The role of potential modifiers of
      the risk and latency period effects needs further investigation. We examined the
      effect of low doses of ionizing radiation (4.5-49.5 cGy) on the risk of
      developing thyroid cancer after long latent periods of up to 54 yr after
      childhood exposure. METHODS: The study population included 10,834 individuals
      irradiated against tinea capitis in the 1950s and two matched nonirradiated
      groups (general population and siblings) for comparison. Cancer statistics and
      vital status data were obtained from national registries, updated to December
      2002. Excess relative and absolute risks [excess relative risk per gray (ERR/Gy),
      excess absolute risk (EAR)] were estimated using Poisson regression for survival
      analysis. RESULTS: Within the study period, 159 cases of thyroid cancer were
      diagnosed. Total ERR/Gy and excess absolute risk per gray per 10(4) person-years
      for developing thyroid cancer reached 20.2 (95% confidence interval 11.8-32.3)
      and 9.9 (95% confidence interval 5.7-14.7), respectively. The risk was positively
      associated with dose and negatively associated with age at exposure. ERR/Gy was
      significantly elevated 10-19 yr after exposure, peaking at 20-30 yr, and
      decreasing dramatically (although still significantly elevated) 40 yr after
      exposure. CONCLUSIONS: Our findings agree with patterns of risk modification seen
      in most studies of radiation-induced thyroid cancer, although risk per unit dose
      seems higher. Our data show that 40 yr after irradiation, ERR decreases
      dramatically, although remaining significantly elevated. The hypothesis of
      different genetic susceptibility of the Jewish population deserves further
      exploration.

PMID- 17018662
TI  - Positive association of obesity with single nucleotide polymorphisms of syndecan
      3 in the Korean population.
AB  - CONTEXT: Very recently the unforeseen role of syndecan 3 (SDC3), a family of
      membrane-bound heparin sulfate proteoglycans, in the regulation of energy balance
      has been discovered in the Sdc3 null female mice. OBJECTIVE: The objective of the
      study was to test the hypothesis that single nucleotide polymorphisms (SNPs) in
      SDC3 are associated with obesity in the Korean population.
      DESIGN/SETTING/SUBJECTS: We conducted a population-based cohort study consisting
      of 229 control and 245 study subjects and a second independent study consisting
      of 192 control and 115 study subjects. MAIN OUTCOME MEASUREMENT: Body mass index
      (BMI) was measured. RESULTS: First, Sdc3 mRNA expression in the brain of ob/ob
      mice was profoundly increased, compared with control mice. Next, all three
      nonsynonymous SNPs [T271I (rs2282440, C>T), D245N (rs4949184, C>T), and V150I
      (rs2491132, C>T)] in the SDC3 gene in control female subjects (BMI < 23, n = 229)
      and obese female subjects (BMI > 30, n = 245) were genotyped. We demonstrated the
      presence of clear ethnic differences in three nonsynonymous SDC3 SNPs among
      African-Americans, Chinese, Europeans, and Koreans. Of three SNPs in SDC3,
      rs4949184 was not associated with obesity and the other two SNPs (rs2282440 and
      rs2491132) were strongly associated with obesity (P < 0.0001), and the results
      were confirmed in the second independent study group. Haplotype analysis also
      revealed strong association with obesity (chi2 = 76.92, P < 0.000001).
      CONCLUSIONS: There are ethnic differences in the SDC3 polymorphisms, and the
      polymorphisms are strongly associated with obesity.

PMID- 17018663
TI  - Creating an interactive Web-based e-learning course: a practical introduction for
      radiologists.
AB  - With the development of e-learning and its ability to provide rich animated
      content rapidly to a wide audience, new methods for teaching medical imaging have
      evolved. E-learning tools allow building of learner-focused structured courses.
      Standards such as shareable content object reference model (SCORM) or Aviation
      Industry Computer-based Training Committee (AICC) guidelines and recommendations
      provide the framework required to combine text, images, videos, animations, and
      quizzes for learning assessment, even if each of these elements is created with
      different software. The main features to consider when choosing a learning
      management system are content management, assessment and reporting tools,
      customization options, course delivery, administration, and security. The tools
      for building a Web-based course with pages containing text, images, videos, and
      Flash animations are now accessible to any radiologist. Open-source learning
      management systems and content authoring software are available at no cost. The
      authors developed e-MRI.com, a free Web-based e-learning course with interactive
      animations and simulations, self-tests, and clinical cases to demonstrate the
      potential of the latest advances in e-learning and pedagogy applied to magnetic
      resonance imaging physics.

PMID- 17018665
TI  - Falling wrinklies.

PMID- 17018667
TI  - Unalterable host factors? A social epidemiologist's view of the Haddon matrix.

PMID- 17018668
TI  - The costs of fatal and non-fatal falls among older adults.
AB  - OBJECTIVE: To estimate the incidence and direct medical costs for fatal and non
      fatal fall injuries among US adults aged >or=65 years in 2000, for three
      treatment settings stratified by age, sex, body region, and type of injury.
      METHODS: Incidence data came from the 2000 National Vital Statistics System, 2001
      National Electronic Injury Surveillance System-All Injury Program, 2000 Health
      Care Utilization Program National Inpatient Sample, and 1999 Medical Expenditure
      Panel Survey. Costs for fatal falls came from Incidence and economic burden of
      injuries in the United States; costs for non-fatal falls were based on claims
      from the 1998 and 1999 Medicare fee-for-service 5% Standard Analytical Files. A
      case crossover approach was used to compare the monthly costs before and after
      the fall. RESULTS: In 2000, there were almost 10 300 fatal and 2.6 million
      medically treated non-fatal fall related injuries. Direct medical costs totaled
      0.2 billion dollars for fatal and 19 billion dollars for non-fatal injuries. Of
      the non-fatal injury costs, 63% (12 billion dollars ) were for hospitalizations,
      21% (4 billion dollars) were for emergency department visits, and 16% (3 billion
      dollars) were for treatment in outpatient settings. Medical expenditures for
      women, who comprised 58% of the older adult population, were 2-3 times higher
      than for men for all medical treatment settings. Fractures accounted for just 35%
      of non-fatal injuries but 61% of costs. CONCLUSIONS: Fall related injuries among
      older adults, especially among older women, are associated with substantial
      economic costs. Implementing effective intervention strategies could appreciably
      decrease the incidence and healthcare costs of these injuries.

PMID- 17018669
TI  - Reducing hazard related falls in people 75 years and older with significant
      visual impairment: how did a successful program work?
AB  - BACKGROUND: In a randomized controlled trial testing a home safety program
      designed to prevent falls in older people with severe visual impairment, it was
      shown that the program, delivered by an experienced occupational therapist,
      significantly reduced the numbers of falls both at home and away from home.
      OBJECTIVES: To investigate whether the success of the home safety assessment and
      modification intervention in reducing falls resulted directly from modification
      of home hazards or from behavioral modifications, or both. METHODS: Participants
      were 391 community living women and men aged 75 years and older with visual
      acuity 6/24 meters or worse; 92% (361 of 391) completed one year of follow up.
      Main outcome measures were type and number of hazards and risky behavior
      identified in the home and garden of those receiving the home safety program,
      compliance with home safety recommendations reported at six months, location of
      all falls for all study participants during the trial, and environmental hazards
      associated with each fall. RESULTS: The numbers of falls at home related to an
      environmental hazard and those with no hazard involved were both reduced by the
      home safety program (n = 100 participants) compared with the group receiving
      social visits (n = 96) (incidence rate ratios = 0.40 (95% confidence interval,
      0.21 to 0.74) and 0.43 (0.21 to 0.90), respectively). CONCLUSIONS: The overall
      reduction in falls by the home safety program must result from some mechanism in
      addition to the removal or modification of hazards or provision of new equipment.

PMID- 17018670
TI  - Unspecified falls among youth: predictors of coding specificity in the emergency
      department.
AB  - BACKGROUND: Deficiencies in emergency department (ED) charting is a common
      international problem. While unintentional falls account for the largest
      proportion of injury related ED visits by youth, insufficient charting details
      result in more than one third of these falls being coded as "unspecified". Non
      specific coding compromises the utility of injury surveillance data. OBJECTIVE:
      To re-examine the ED charts of unspecified youth falls to determine the
      possibility of assigning more specific codes. METHODS: 400 ED charts for youth
      (aged 0-19 years) treated at four EDs in an urban Canadian health region between
      1997 and 1999 and coded as "Other or unspecified fall" (ICD-9 E888) were randomly
      selected. A structured chart review was completed and a blinded nosologist
      recoded the cause of injury using the extracted data. Differences in coding
      specificity were compared with the original data, and logistic regression was
      undertaken to examine variables that predicted assignment of a specific E-code.
      RESULTS: A more specific code was assigned to 46% of cases initially coded as
      unspecified. Of these, 73% were recoded as "Slips, trips, and stumbles" (E885),
      which still lacks the specificity required for injury prevention planning; 2% of
      charts had no fall documented. Multivariate analysis revealed that dichotomized
      injury severity (adjusted odds ratio (OR) = 1.75 (95% confidence interval, 1.11
      to 2.78)), arrival at the ED by ambulance (adjusted OR = 5.41 (1.07 to 27.0)),
      and the availability of nurse's notes or triage forms, or both, in the chart
      (adjusted OR = 3.75 (2.17 to 6.45)) were the strongest predictors of a more
      specific E-code assignment. CONCLUSIONS: Deficiencies in both chart documentation
      and coding specificity contribute to the use of non-specific E-codes. More
      comprehensive triage coding, improved chart documentation, and alternative
      methods of data collection in the acute care setting are required to improve ED
      injury surveillance initiatives.

PMID- 17018671
TI  - The criminal purchase of firearm ammunition.
AB  - OBJECTIVE: Laws that prohibit certain individuals from owning firearms also
      pertain to ammunition. Whereas retail sales of firearms to criminals are
      regularly disrupted by instant background checks, sales of ammunition are
      essentially unchecked and the rate at which criminals acquire ammunition is
      unknown. This research describes the ammunition market and estimates the rate at
      which criminals are acquiring ammunition. DESIGN: Criminal background checks
      conducted on individuals purchasing ammunition in the City of Los Angeles in
      April and May 2004. SETTING: Los Angeles, CA, USA. SUBJECTS: Ammunition
      purchasers. MAIN OUTCOME MEASURES: Criminal activity that prohibits one from
      owning, purchasing, or possessing ammunition. RESULTS: 2.6% (95% CI 1.9% to 3.2%)
      of ammunition purchasers had a prior felony conviction or another condition that
      prohibited them from possessing ammunition. During the study period prohibited
      possessors purchased 10,050 rounds of ammunition in Los Angeles. CONCLUSIONS:
      These estimates suggest that monitoring ammunition transactions may help reduce
      the supply of ammunition to criminals and the frequency of injuries from
      felonious gun assaults. Such a record can also provide information for generating
      leads on illegal firearm possession.

PMID- 17018672
TI  - The influence of local politicians on pedestrian safety.
AB  - AIM: To determine whether local politicians influence the distribution of traffic
      calming measures. METHODS: Longitudinal ecological study in two UK cities. Local
      political constituencies were categorized by representation by members of the
      cabinet structure as a marker of influence. The density of traffic calming
      features per political area, adjusted for the historical pattern of road
      injuries, was compared between cabinet represented and non-represented areas.
      RESULTS: Traffic calming density was significantly associated with cabinet
      representation status, adjusted for historical collision risk (risk ratio 2.77,
      95% confidence interval 1.37 to 5.61). CONCLUSION: These results support the
      hypothesis that senior local politicians are effective advocates for enhancing
      safety in their areas.

PMID- 17018674
TI  - Car manufacturers and global road safety: a word frequency analysis of road
      safety documents.
AB  - OBJECTIVE: The World Bank believes that the car manufacturers can make a valuable
      contribution to road safety in poor countries and has established the Global Road
      Safety Partnership (GRSP) for this purpose. However, some commentators are
      sceptical. The authors examined road safety policy documents to assess the extent
      of any bias. DESIGN: Word frequency analyses of road safety policy documents from
      the World Health Organization (WHO) and the GRSP. MAIN OUTCOME MEASURES: The
      relative occurrence of key road safety terms was quantified by calculating a word
      prevalence ratio with 95% confidence intervals. Terms for which there was a
      fourfold difference in prevalence between the documents were tabulated. RESULTS:
      Compared to WHO's World report on road traffic injury prevention, the GRSP road
      safety documents were substantially less likely to use the words speed, speed
      limits, child restraint, pedestrian, public transport, walking, and cycling, but
      substantially more likely to use the words school, campaign, driver training, and
      billboard. CONCLUSIONS: There are important differences in emphasis in road
      safety policy documents prepared by WHO and the GRSP. Vigilance is needed to
      ensure that the road safety interventions that the car industry supports are
      based on sound evidence of effectiveness.

PMID- 17018673
TI  - Evaluation of Safe Kids Week 2004: age 4 to 9? It's booster seat time!
AB  - OBJECTIVE: To assess the effectiveness of a national one week media campaign
      promoting booster seat use. DESIGN: Pre-test, post-test design based on
      nationally representative random digit dialing telephone survey, with control for
      exposure to campaign. SETTING: Canada. SUBJECTS: Parents of children aged 4-9
      years. INTERVENTIONS: During a one week campaign in May 2004, information on
      booster seat use was distributed via a national media campaign, retail stores,
      medical clinics, and community events. Information included pamphlets with
      guidelines for booster seat use, as well as a growth chart (designed by Safe Kids
      Canada) to assist parents in determining if their child should be using a booster
      seat. Assessing seat belt fit was described in detail on the growth chart. MAIN
      OUTCOME MEASURES: Knowledge, attitudes, and self-reported behaviors regarding
      booster seat use. RESULTS: Respondents in the group exposed to the campaign were
      twice as likely to report using a booster seat with lap and shoulder belt for
      their child (47%), compared to those in the pre-test (24%) and the unexposed
      (23%) groups (p<0.001). However, only small differences in general knowledge
      regarding booster seat use were found between the groups. CONCLUSIONS: A one week
      national media campaign substantially increased self-reported use of booster
      seats. Parents did not remember details of the campaign content, but did remember
      implications for their own child.

PMID- 17018675
TI  - Emergency department screening for risk for post-traumatic stress disorder among
      injured children.
AB  - OBJECTIVE: To discuss the successes and challenges associated with the
      implementation of a post-traumatic stress disorder (PTSD) screening tool in two
      pediatric emergency departments (ED). METHODS: The STEPP screening tool has been
      developed previously on an inpatient population of motor vehicle trauma patients.
      It was applied here to the general ED population at two different pediatric
      trauma centers. Nurse screeners were trained and a convenience sample of patients
      with unintentional injuries who met study criteria were screened in the ED.
      Feedback from nurse screeners was obtained. RESULTS: The process of implementing
      a screening tool to identify patients and their families significantly at risk
      for PTSD symptomatology presented some barriers, but overall acceptability of the
      process was high for both the emergency department staff and the patient.
      Recommendations for others considering implementation of screening programs in
      the ED are offered. CONCLUSIONS: Future research using screening protocols in the
      ED should, in their design, attempt to capitalize on the successes identified in
      the current protocol and circumvent barriers also encountered.

PMID- 17018676
TI  - Intentional injury mortality in the European Union: how many more lives could be
      saved?
AB  - OBJECTIVE: To explore the scope for reducing the number of intentional injury
      deaths, hypothesizing that all European Union (EU) countries are able to match
      the experience of the country with the lowest mortality rate for intentional
      injuries. DESIGN: Intentional injury mortality data for the three last available
      years and denominator population estimates were obtained from the World Health
      Organisation mortality database for the 22 EU countries with more than one
      million population. To estimate the potential saving of lives, the yearly average
      age adjusted injury mortality rates were calculated. This issue done for children
      (0-14), adults (15-64), and elderly people (65 and over), both including and
      excluding deaths from undetermined cause. MAIN OUTCOME MEASURES: Number of lives
      that might potentially be saved if all EU member states matched the lowest
      intentional injury rate reported by an EU member state. RESULTS: Over 73% of all
      intentional injury deaths could have been avoided if all EU countries matched the
      country with the lowest intentional injury mortality rate. EU member states would
      have suffered about 600 fewer intentional injury deaths in children, about 40 000
      fewer adult deaths, and over 14 000 fewer intentional injury deaths in the
      elderly. This amounts to over 55 000 lives in a single year. CONCLUSIONS: Many
      lives lost through injury might be saved if all countries were to achieve the
      lowest intentional injury mortality rates reported in the EU. How this
      theoretical observation might be translated into practice needs to be further
      explored as the international variation in intentional injury mortality rates in
      the EU results from a range of factors.

PMID- 17018677
TI  - Identification of strategies to prevent death after pesticide self-poisoning
      using a Haddon matrix.
AB  - Despite pesticide self-poisoning causing around 300 000 deaths each year in the
      rural Asia Pacific region, no comprehensive public health response has yet been
      formulated. The authors have developed a Haddon matrix to identify factors that
      increase the risk of fatal rather than non-fatal pesticide self-poisoning in Sri
      Lanka. Many important host factors such as age, gender, and genetics are not
      alterable; factors that could be changed-alcohol use and mental health-have
      previously proved difficult to change. Interventions affecting agent or
      environmental factors may be easier to implement and more effective, in
      particular those limiting the human toxicity and accessibility of the pesticides,
      and the quality, affordability, and accessibility of health care in the
      community. Controlled studies are required to identify effective strategies for
      prevention and harm minimization and to garner political support for making the
      changes necessary to reduce this waste of life. Lessons learnt from Sri Lanka are
      likely to be highly relevant for much of rural Asia.

PMID- 17018678
TI  - Classifying undetermined poisoning deaths.
AB  - OBJECTIVE: To classify poisoning deaths of undetermined intent as either suicide
      or unintentional and to estimate the extent of underreported poisoning suicides.
      METHODS: Based on 2002 statewide death certificate and medical examiner data in
      Utah, the authors randomly selected one half of undetermined and unintentional
      poisoning deaths for data abstraction and included all suicides. Bivariate
      analyses assessed differences in demographics, death characteristics, forensic
      toxicology results, mental health history, and other potentially contributing
      factors. Classification and regression tree (CART) analysis used information from
      unintentional and suicide poisoning deaths to create a classification tree that
      was applied to undetermined poisoning deaths. RESULTS: The authors analyzed 41
      unintentional, 87 suicide, and 84 undetermined poisonings. Undetermined and
      unintentional decedents were similar in the presence of opiates, physical health
      problems, and drug abuse. Although none of the undetermined decedents left a
      suicide note, previous attempt or intent to commit suicide was reported for 11
      (13%) of these cases. CART analysis identified suicidal behavior, drug abuse,
      physical health problems, depressed mood, and age as discriminating between
      suicide and unintentional poisoning. It is estimated that suicide rates related
      to poisoning are underreported by approximately 30% and overall suicide rates by
      10%. Unintentional poisoning death rates were underreported by 61%. CONCLUSIONS:
      This study suggests that manner of death determination relies on circumstance
      dependent variables that may not be consistently captured by medical examiners.
      Underreporting of suicide rates has important implications in policy development,
      research funding, and evaluation of prevention programs.

PMID- 17018679
TI  - Impact of a community based fire prevention intervention on fire safety knowledge
      and behavior in elementary school children.
AB  - The objective of this study was to determine the impact of a community based fire
      prevention intervention directed only to parents on the fire safety knowledge and
      behavior in elementary school children. This was a prospective, quasi-randomized
      controlled study in which third and fourth grade students from two elementary
      schools in an urban, poor, minority community completed knowledge/behavior
      surveys at baseline and following completion of the intervention. The
      intervention group received an in-home visit from fire department personnel who
      installed free lithium smoke detectors and provided a fire escape plan. After
      accounting for a small difference in baseline summary scores of knowledge and
      behavior between the control and intervention groups, this study found a modest
      improvement in fire safety behavior among children whose families received a fire
      prevention intervention reflecting a change in household fire safety practices.
      However, there was no significant change in fire safety knowledge.

PMID- 17018680
TI  - Determining objective injury prevention priorities.
AB  - BACKGROUND AND OBJECTIVE: Finite injury prevention resources make the
      establishment of prevention priorities essential. Toward this end, the US
      National Trauma Data Bank (NTDB) for 2000 to 2004 was accessed and four injury
      prevention priority scores (one previously defined and three new scores) were
      computed. METHODS: An injury prevention priority score (IPPS) was calculated
      based on the frequency of an injury mechanism and the median injury severity
      score. In addition, a mortality priority score (Mort-PS), a hospital charge
      priority score (Charge-PS), and a years of potential life lost (YPLL-PS) priority
      score were calculated for the 13 most common injury mechanisms. RESULTS: There
      was variability across the four scores, but motor vehicle traffic, firearm
      related, and fall injuries ranked high on all four of the priority criteria.
      Multiple criteria should be considered when assessing injury burden. CONCLUSIONS:
      The methods presented here can help prioritize injuries and support more
      objective public policies.

PMID- 17018681
TI  - School based programs for prevention of violence: do they work?

PMID- 17018682
TI  - A laboratory strategy for genotyping haemoglobin H disease in the Chinese.
AB  - BACKGROUND: The thalassaemias are the commonest blood disorders worldwide, with
      South East Asia and southern China as areas of high prevalence. Accurate
      diagnosis of these disorders helps in clinical management with improved outcome.
      METHODS: The alpha-globin genotypes of 100 Chinese patients in Hong Kong with
      haemoglobin H (Hb H) disease were characterised. Single-tube multiplex gap-PCR
      was used to detect --(SEA), -alpha(3.7) and -alpha(4.2), while Hb CS, Hb QS and
      codon 30 (DeltaGAG) were identified by single-tube multiplex amplification
      refractory mutation system (ARMS). Automated direct nucleotide sequencing of the
      amplified alpha2- and alpha1-globin genes was performed to characterise other non
      deletional alpha-thalassaemia determinants. RESULTS: In the 100 cases studied, 99
      cases had --(SEA) in combination with deletional alpha(+)-thalassaemia or non
      deletional alpha-globin gene mutation involving the alpha2-globin gene. In 70
      cases of the deletional form, 43 cases showed the genotype of (--(SEA)/
      alpha(3.7)) and 27 cases of (--(SEA)/-alpha(4.2)). Three of the 27 cases of (-
      (SEA)/-alpha(4.2)) were found to have Hb Q-Thailand linked in-cis with 
      alpha(4.2). The remaining 30 cases were of non-deletional form with the following
      genotypes: 11 cases of (--(SEA)/alpha(HbCS)alpha), 9 cases of (-
      (SEA)/alpha(HbQS)alpha), 3 cases of (--(SEA)/alpha(cd30 (DeltaGAG))alpha), 3
      cases of (--(SEA)/alpha(cd31)alpha), 2 cases of (--(SEA)/alpha(poly-A)alpha), 1
      case of (--(SEA)/alpha(HbWestmead)alpha) and 1 case of (--(non
      SEA)/alpha(HbQS)alpha). CONCLUSIONS: Based on two rapid diagnostic tests,
      multiplex gap-PCR and multiplex ARMS, more than 90% of the cases were genetically
      characterised. This laboratory strategy should be widely applicable for genetic
      diagnosis of alpha-thalassaemia.

PMID- 17018683
TI  - CD56-positive haematological neoplasms of the skin: a multicentre study of the
      Cutaneous Lymphoma Project Group of the European Organisation for Research and
      Treatment of Cancer.
AB  - BACKGROUND: Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule,
      are characterised in most cases by a highly aggressive clinical course and a poor
      prognosis. However, prognostic subsets within the CD56+ group have been difficult
      to identify due to the lack of uniform clinicopathological and immunophenotypical
      criteria. METHODS: A multicentre study was conducted by the Cutaneous Lymphoma
      Task Force of the European Organisation for Research and Treatment of Cancer to
      define prognostic parameters and establish diagnostic and therapeutic guidelines
      for CD56+ haematological neoplasms presenting primarily in the skin. RESULTS:
      Four different subtypes of lymphoproliferations with CD56 expression were
      identified: (1) haematodermic neoplasm; (2) skin infiltration as the first
      manifestation of CD56+ acute myeloid leukaemia; (3) nasal-type extranodal natural
      killer/T-cell lymphoma; and (4) "classical" cases of cutaneous T-cell lymphoma
      (CTCL) with co-expression of the CD56 molecule. Patients in the first three
      groups had a poor outcome (93% died) with a median survival rate of 11 months
      (95% CI 2-72 months), whereas all patients with CD56+ CTCL were alive at the last
      follow-up. CONCLUSION: Results show that CD56+ cutaneous lymphoproliferative
      disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is
      therefore clinically important to separate CD56+ CTCL from the remaining CD56+
      haematological disorders.

PMID- 17018684
TI  - Ovarian clear cell adenocarcinoma: a continuing enigma.
AB  - Ovarian clear cell adenocarcinomas (OCCAs) account for <5% of all ovarian
      malignancies. Compared to other epithelial ovarian cancer (EOC) subtypes, when at
      an advanced stage, they are associated with a poorer prognosis and are relatively
      resistant to conventional platinum-based chemotherapy. By contrast, early-stage
      clear cell ovarian cancer carries a relatively good prognosis. Hence, there is a
      need to improve our understanding of its pathobiology in order to optimise
      currently available treatments and develop new therapeutic strategies. This
      review summarises the currently available literature regarding the pathogenesis
      of OCCA, its molecular genetic features and postulated molecular mechanisms that
      underlie its chemoresistant phenotype. Marked similarities with clear cell
      carcinomas of the kidney and endometrium have been noted by some investigators,
      raising interesting possibilities regarding novel therapeutic approaches.
      Unfortunately, most studies on OCCA have hitherto been hampered by insufficient
      sample sizes, leaving many key issues unresolved. It is envisaged that in the
      future, high-resolution genomic and gene-expression microarray studies
      incorporating larger sample sizes will lead to the characterisation of the key
      molecular players in OCCA biology, which may potentially lead to the
      identification of novel targets for therapeutic development.

PMID- 17018685
TI  - Gene transfer of soluble transforming growth factor type II receptor by in vivo
      electroporation attenuates lung injury and fibrosis.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has the potential to
      induce acute inflammation and apoptosis in lung epithelial cells and plays a
      central role in subsequent fibrosis. AIMS: To examine a new anti-TGF-beta1
      therapy against lung injury and fibrosis, which comprises the transfection of
      soluble TGF type II receptor (sTGFRII) gene into skeletal muscles by in vivo
      electroporation. METHODS: Soluble TGFRII was detectable between 1 and 14 days in
      the serum and significantly increased between 3 and 10 days after gene transfer
      into muscles. Based on these findings, the sTGFRII gene was injected at 3 days
      before or 4 days after the bleomycin instillation in order to examine the
      significance of TGF-beta1 on the early inflammatory phase (day 0 to day 7) or the
      fibrotic phase (day 7 to day 14) in this model. RESULTS: Transfection of sTGFRII
      gene at 3 days before or 4 days after bleomycin instillation significantly
      attenuated apoptosis, injury, and fibrosis at 7 or 14 days, respectively. This
      method does not require the use of viral vector or neutralising antibody, and it
      is therefore possible to avoid problems regarding the pathogenicity of the viral
      vector or immunocomplex. CONCLUSIONS: This novel anti-TGF-beta1 strategy may have
      clinical application in the treatment of lung injury and fibrosis.

PMID- 17018686
TI  - Expression of c-kit in human osteosarcoma and its relevance as a prognostic
      marker.
AB  - AIMS: To examine the prognostic relevance of c-kit expression in human
      osteosarcomas and to evaluate the mutation status in exon 9 and exon 11 of the c
      kit gene. METHODS: c-kit expression was examined in 100 human osteosarcomas by
      immunohistochemistry using paraffin embedded tumour tissues, and capillary
      sequencing of genomic DNA was performed to search for mutations in exons 9 and 11
      of the c-kit gene. RESULTS: 20 osteosarcomas showed c-kit expression ranging from
      5% to 90% (mean 5.9%; SD 16.74%). Furthermore, DNA sequences of exon 9 and exon
      11 of the c-kit gene were not altered in these tumours. Overall and disease free
      survival analysis did not reveal any differences between patients with
      osteosarcoma with c-kit expression and those with c-kit negative tumours.
      CONCLUSIONS: C-kit expression is not a prognostic marker in patients with
      osteosarcoma. The protein expression is not linked to mutations in exon 9 or exon
      11 of the c-kit gene. Therefore, these exons may not function as targets for
      treatment modalities based on the suppression of c-kit tyrosine kinase activity.

PMID- 17018687
TI  - Consequences of combining cystic fibrosis- and non-cystic fibrosis-derived
      Pseudomonas aeruginosa antibiotic susceptibility results in hospital
      antibiograms.
AB  - BACKGROUND: In preparing hospital antibiograms for individual organisms and
      antibiotics, laboratories often combine susceptibility data for isolates from a
      variety of sources and patient types. If results from patients with known
      resistance patterns that vary from normal are included, the overall
      susceptibility value for the institution could be misleadingly skewed. OBJECTIVE:
      To assess the degree of bias introduced into a hospital antibiogram by combining
      cystic fibrosis (CF) and non-CF isolates of Pseudomonas aeruginosa to produce one
      hospital-wide percent susceptible figure for each tested antibiotic. METHODS: A
      retrospective analysis was conducted of an academic, tertiary care medical
      center's microbiology database. We examined quarterly and annual susceptibility
      data from 2004, comparing non-CF data with combined susceptibility data for 10
      antibiotics within each quarter, as well as those reported in the annual
      antibiogram. Differences were assessed for statistical significance using chi(2)
      testing with Bonferroni correction. RESULTS: Large differences were observed
      between non-CF and combined percent susceptible data in the 4 quarters
      (aminoglycosides 3% vs 20%, fluoroquinolones 2% vs 18%, respectively) and when
      comparing annual non-CF (n = 191) with annual combined (n = 266) data. With the
      annual figures, these differences were frequently statistically significant (70%
      vs 58%, 91% vs 83%, 85% vs 70%, and 72% vs 60% for gentamicin, tobramycin,
      amikacin, and gatifloxacin/levofloxacin, respectively; all p< or =0.01).
      CONCLUSIONS: Combining CF and non-CF P. aeruginosa susceptibility into one
      percent susceptibility value for all isolates may produce figures that
      underestimate the activity of some antibiotic classes against non-CF isolates.
      Clinicians may make less than optimal empiric antibiotic selection choices based
      on such data.

PMID- 17018688
TI  - Polymyxin B and doxycycline use in patients with multidrug-resistant
      Acinetobacter baumannii infections in the intensive care unit.
AB  - BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDR-Ab) has emerged as
      an increasingly problematic cause of hospital-acquired infections in the
      intensive care unit (ICU). MDR-Ab is resistant to most standard antimicrobials
      but often retains susceptibility to polymyxin B and doxycycline. OBJECTIVE: To
      evaluate the efficacy and toxicity of polymyxin B and doxycycline in the
      treatment of MDR-Ab infections. METHODS: A retrospective chart review was
      conducted between March 2002 and May 2005 in patients who received doxycycline or
      polymyxin B for treatment of MDR-Ab infections in ICUs within Grady Memorial
      Hospital, Atlanta, GA. RESULTS: Thirty-seven patients with MDR-Ab infections were
      treated with polymyxin B or doxycycline. Median age was 41 years and median ICU
      length of stay was 18 days prior to acquisition of MDR-Ab. Clinical cure was
      observed in 22 of 29 (76%) evaluable patients treated with polymyxin B and 2 of 4
      (50%) patients treated with doxycycline. In patients with follow-up cultures,
      microbiological cure was observed in 17 of 21 (81%) patients treated with
      polymyxin B and 2 of 3 (67%) patients treated with doxycycline. Nephrotoxicity
      developed in 21% (7 of 33) of patients who received polymyxin B. Neurotoxicity
      was observed in 2 (6%) patients who received polymyxin B. No adverse reactions
      were observed with doxycycline. Overall, crude mortality was 27% (9 of 33) and
      75% (3 of 4) among those who received polymyxin B and doxycycline, respectively.
      Three (9%) deaths were attributed to polymyxin B treatment failure, and no deaths
      were attributed to doxycycline treatment failure. CONCLUSIONS: Polymyxin B was
      effectively used to treat a substantial proportion of critically ill patients
      with MDR-Ab infection and was associated with a similar rate of nephrotoxicity as
      previously reported. Doxycycline monotherapy was used in a limited number of
      patients for the treatment of MDR-Ab; further evaluation of its efficacy in
      larger numbers of patients is warranted.

PMID- 17018689
TI  - Large-scale transcriptional analysis of bovine embryo biopsies in relation to
      pregnancy success after transfer to recipients.
AB  - The purpose of this work is to address the relationship between transcriptional
      profile of embryos and the pregnancy success based on gene expression analysis of
      blastocyst biopsies taken prior to transfer to recipients. Biopsies (30-40% of
      the intact embryo) were taken from in vitro-produced day 7 blastocysts (n = 118),
      and 60-70% were transferred to recipients after reexpansion. Based on the success
      of pregnancy, biopsies were pooled in three groups (each 10 biopsies) namely:
      those resulting in no pregnancy (G1), resorbed embryos (G2), and those resulting
      in calf delivery (G3). Gene expression analysis of these groups was performed
      using home-made bovine preimplantation-specific cDNA array (219 clones) and
      BlueChip (with approximately 2,000 clones). Microarray data analysis results
      revealed a total of 52 and 58 genes were differentially regulated during
      comparison between G1 vs. G3 and G2 vs. G3. Biopsies resulted in calf delivery
      were enriched with genes necessary for implantation (COX2 and CDX2), carbohydrate
      metabolism (ALOX15), growth factor (BMP15), signal transduction (PLAU), and
      placenta-specific 8 (PLAC8). Biopsies from embryos resulting in resorption are
      enriched with transcripts involved protein phosphorylation (KRT8), plasma
      membrane (OCLN), and glucose metabolism (PGK1 and AKR1B1). Biopsies from embryos
      resulting in no pregnancy are enriched with transcripts involved inflammatory
      cytokines (TNF), protein amino acid binding (EEF1A1), transcription factors
      (MSX1, PTTG1), glucose metabolism (PGK1, AKR1B1), and CD9, which is an inhibitor
      of implantation. In conclusion, we generated direct candidates of blastocyst
      specific genes which may play an important role in determining the fate of the
      embryo after transfer.

PMID- 17018690
TI  - Angiopoietin-1 and vascular endothelial growth factor induce expression of
      inflammatory cytokines before angiogenesis.
AB  - The purpose of this study was to identify novel transcriptional events occurring
      in the aortic wall before angiogenesis. We used a defined tissue culture system
      that takes advantage of the capacity of rat aortic rings to generate neovessels
      ex vivo in response to angiogenic factor stimulation. Total RNA isolated from
      aortic rings 18 h posttreatment with angiopoietin (Ang)-1 or vascular endothelial
      growth factor (VEGF) was used to probe oligonucleotide microarrays. Many genes
      were up- or downregulated by either Ang-1 or VEGF, with a subset being affected
      by treatment with both growth factors. Grouping of genes by biological function
      revealed that Ang-1 and VEGF both upregulated a host of immune-related genes
      including many inflammatory cytokines. A mixture of the Ang-1- and VEGF-induced
      cytokines stimulated the spontaneous angiogenic response of aortic rings and was
      synergistic with a low dose of recombinant VEGF. This effect was associated with
      enhanced recruitment of adventitial macrophages and dendritic cells in the
      angiogenic outgrowths. Thus Ang-1 and VEGF activate the innate immune system of
      the vessel wall, stimulating the production of proangiogenic inflammatory
      cytokines before the emergence of neovessels. This hitherto unreported feature of
      the angiogenic response might represent an important early component of the
      cellular and molecular cascade responsible for the angiogenic response of the
      aortic wall.

PMID- 17018691
TI  - A comparison of the antagonist affinities for the Gi- and Gs-coupled states of
      the human adenosine A1-receptor.
AB  - The antagonist affinity for a given receptor is traditionally considered to be
      constant, reflecting the chemical nature of the specific ligand-receptor
      interaction. However, recent observations with all three beta-adrenoceptors have
      cast doubt on this basic pharmacological principle. The extent to which this
      finding applies to other G protein-coupled receptors and their interaction with
      different G proteins is unknown. Therefore, we studied the influence of different
      agonists on antagonist affinity measurements for Gi- and Gs-coupled conformations
      of the adenosine A1-receptor in Chinese hamster ovary cells stably expressing the
      human adenosine A1-receptor and a cAMP-response element (CRE)-secreted placental
      alkaline phosphatase reporter gene. Gi-coupled inhibition of [3H]cAMP
      accumulation via the A1-receptor was observed at low concentrations of agonist;
      however, a small increase in [3H]cAMP accumulation was also seen at higher
      agonist concentrations. This biphasic response was more evident for A1-stimulated
      CRE-gene transcription. The inhibitory component was abolished by pretreatment
      with pertussis toxin, whereas the stimulatory component was augmented, suggesting
      that the responses were due to an A1-Gi-coupled inhibition followed by an A1-Gs
      coupled stimulation. However, the antagonist affinity values measured at the Gi
      coupled and Gs-coupled conformations of the receptor were the same in both
      functional responses and whole-cell binding. Thus, in marked contrast to the beta
      adrenoceptors, the A1-receptor conforms to the long-held principle of
      pharmacology that antagonist affinity measurements are constant regardless of the
      response being measured and the competing agonist used to stimulate that
      response. This was true even when the receptor was shown, in the same assay, to
      exist in two different conformational states coupled to two different G proteins.

PMID- 17018692
TI  - Lack of the aryl hydrocarbon receptor leads to impaired activation of AKT/protein
      kinase B and enhanced sensitivity to apoptosis induced via the intrinsic pathway.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor
      that is best known for its role in mediating the toxicity of many environmental
      contaminants such as 2,3,7,8 tetrachlorodibenzo-p-dioxin. However, the endogenous
      role of AHR, especially with respect to the apoptotic process, is largely unknown
      and contradictory. In this report, we have used a mouse hepatoma cell line
      (Hepa1c1c7) and its AHR-deficient derivative (LA1) to examine the effect of
      differing AHR levels on apoptosis susceptibility, in particular, apoptosis
      regulated by the intrinsic pathway. Toward this end, the cells were subjected to
      UV irradiation, hydrogen peroxide, and serum starvation. Analyses of a number of
      different endpoints of apoptosis revealed that the LA1 cells were more sensitive
      to these stresses than the wild-type cells, indicating that the AHR plays a
      cytoprotective role in the face of stimuli that initiate the intrinsic apoptotic
      pathway. A direct role of the AHR in mediating this effect was confirmed using
      both pharmacological and molecular approaches. Further analyses imply that lack
      of the AHR leads to an impaired survival response mediated by
      phosphatidylinositol 3'-OH kinase-Akt/protein kinase B and, to a lesser degree,
      epidermal growth factor receptor activation. These findings indicate that
      exploring the use of the AHR antagonist as agents that enhance the proapoptotic
      actions of cancer therapies may be a valid approach.

PMID- 17018693
TI  - Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities.
AB  - Increased Rho kinase (ROCK) activity contributes to smooth muscle contraction and
      regulates blood pressure homeostasis. We hypothesized that potent and selective
      ROCK inhibitors with novel structural motifs would help elucidate the functional
      role of ROCK and further explore the therapeutic potential of ROCK inhibition for
      hypertension. In this article, we characterized two aminofurazan-based
      inhibitors, GSK269962A [N-(3-{[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H
      imidazo[4, 5-c]pyridin-6-yl]oxy}phenyl)-4-{[2-(4-morpholinyl)ethyl]
      oxy}benzamide] and SB-7720770-B [4-(7-{[(3S)-3-amino-1-pyrrolidinyl]carbonyl}-1
      ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine], as members of a
      novel class of compounds that potently inhibit ROCK enzymatic activity.
      GSK269962A and SB-772077-B have IC50 values of 1.6 and 5.6 nM toward recombinant
      human ROCK1, respectively. GSK269962A also exhibited more than 30-fold
      selectivity against a panel of serine/threonine kinases. In lipopolysaccharide
      stimulated monocytes, these inhibitors blocked the generation of inflammatory
      cytokines, such as interleukin-6 and tumor necrosis factor-alpha. Furthermore,
      both SB-772077-B and GSK269962A induced vasorelaxation in preconstricted rat
      aorta with an IC50 of 39 and 35 nM, respectively. Oral administration of either
      GSK269962A or SB-772077-B produced a profound dose-dependent reduction of
      systemic blood pressure in spontaneously hypertensive rats. At doses of 1, 3, and
      30 mg/kg, both compounds induced a reduction in blood pressure of approximately
      10, 20, and 50 mm Hg. In addition, administration of SB-772077-B also
      dramatically lowered blood pressure in DOCA salt-induced hypertensive rats. SB
      772077-B and GSK269962A represent a novel class of ROCK inhibitors that have
      profound effects in the vasculature and may enable us to further evaluate the
      potential beneficial effects of ROCK inhibition in animal models of
      cardiovascular as well as other chronic diseases.

PMID- 17018694
TI  - Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons.
AB  - Migraine is a common and disabling neurological disorder that involves activation
      or the perception of activation of the trigeminovascular system. Cannabinoid (CB)
      receptors are present in brain and have been suggested to be antinociceptive.
      Here we determined the effect of cannabinoid receptor activation on neurons with
      trigeminovascular nociceptive input in the rat. Neurons in the trigeminocervical
      complex (TCC) were studied using extracellular electrophysiological techniques.
      Responses to both dural electrical stimulation and cutaneous facial receptive
      field activation of the ophthalmic division of the trigeminal nerve and the
      effect of cannabinoid agonists and antagonists were studied. Nonselective CB
      receptor activation with R(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2, 3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)
      (WIN55,212; 1 mg kg(-1)) inhibited neuronal responses to A-(by 52%) and C-fiber
      (by 44%) afferents, an effect blocked by the CB(1) receptor antagonist SR141716
      [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H
      pyrazole-3-carboxamide; 3 mg kg(-1)] but not the CB2 receptor antagonist AM630 (6
      iodopravadoline; 3 mg kg(-1)). Anandamide (10 mg kg(-1)) was able to inhibit both
      A- and C-fiber-elicited TCC firing, only after transient receptor potential
      vanilloid 1 receptor inhibition. Activation of cannabinoid receptors had no
      effect on cutaneous receptive fields when recorded from TCC neurons. The data
      show that manipulation of CB1 receptors can affect the responses of trigeminal
      neurons with A- and C-fiber inputs from the dura mater. This may be a direct
      effect on neurons in the TCC itself or an effect in discrete areas of the brain
      that innervate these neurons. The data suggest that CB receptors may have
      therapeutic potential in migraine, cluster headache, or other primary headaches,
      although the potential hazards of psychoactive side effects that accompany
      cannabinoid treatments may be complex to overcome.

PMID- 17018695
TI  - Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal
      topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in
      intracranial brain tumor xenografts.
AB  - Despite multimodal treatment options, the response and survival rates for
      patients with malignant gliomas remain dismal. Clinical trials with convection
      enhanced delivery (CED) have recently opened a new window in neuro-oncology to
      the direct delivery of chemotherapeutics to the CNS, circumventing the blood
      brain barrier and reducing systemic side effects. Our previous CED studies with
      liposomal chemotherapeutics have shown promising antitumor activity in rodent
      brain tumor models. In this study, we evaluated a combination of nanoliposomal
      topotecan (nLs-TPT) and pegylated liposomal doxorubicin (PLD) to enhance efficacy
      in our brain tumor models, and to establish a CED treatment capable of improving
      survival from malignant brain tumors. Both liposomal drugs decreased key enzymes
      involved in tumor cell replication in vitro. Synergistic effects of nLs-TPT and
      PLD on U87MG cell death were found. The combination displayed excellent efficacy
      in a CED-based survival study 10 days after tumor cell implantation. Animals in
      the control group and those in singleagent groups had a median survival of less
      than 30 days, whereas the combination group experienced a median survival of more
      than 90 days. We conclude that CED of two liposomal chemotherapeutics (nLs-TPT
      and PLD) may be an effective treatment option for malignant gliomas.

PMID- 17018696
TI  - Hypersomnia as presenting symptom of anti-Ma2-associated encephalitis: case
      study.
AB  - We describe a patient who presented with excessive daytime sleepiness (EDS) and
      was eventually diagnosed with anti-Ma2 encephalitis. Neurological examination
      disclosed somnolence, left palpebral ptosis, and vertical gaze paresis. A brain
      MRI showed high signal intensity in the hypothalamus and each hippocampus. Ma2
      antibodies were found in the patient's serum, and fiberbronchoscopy disclosed a
      lung carcinoma. After three months of steroid treatment, the results of the
      patient's neurological exam became normal. We conclude that anti-Ma2 encephalitis
      may present with mostly isolated EDS and that it may respond to steroids despite
      old age and the presence of an untreated lung cancer.

PMID- 17018697
TI  - The course of neurocognitive functioning in high-grade glioma patients.
AB  - We evaluated the course of neurocognitive functioning in newly diagnosed high
      grade glioma patients and specifically the effect of tumor recurrence. Following
      baseline assessment (after surgery and before radiotherapy), neurocognitive
      functioning was evaluated at 8 and 16 months. Neurocognitive summary measures
      were calculated to detect possible deficits in the domains of (1) information
      processing, (2) psychomotor function, (3) attention, (4) verbal memory, (5)
      working memory, and (6) executive functioning. Repeated-measures analyses of
      covariance were used to evaluate changes over time. Thirty-six patients were
      tested at baseline only. Follow-up data were obtained for 32 patients: 14 had a
      follow-up at 8 months, and 18 had an additional follow-up at 16 months. Between
      baseline and eight months, patients deteriorated in information-processing
      capacity, psychomotor speed, and attentional functioning. Further deterioration
      was observed between 8 and 16 months. Of 32 patients, 15 suffered from tumor
      recurrence before the eight-month follow-up. Compared with recurrence-free
      patients, not only did patients with recurrence have lower information-processing
      capacity, psychomotor speed, and executive functioning, but they also exhibited a
      more pronounced deterioration between baseline and eight-month follow-up. This
      difference could be attributed to the use of antiepileptic drugs in the patient
      group with recurrence. This study showed a marked decline in neurocognitive
      functioning in HGG patients in the course of their disease. Patients with tumor
      progression performed worse on neurocognitive tests than did patients without
      progression, which could be attributed to the use of antiepileptic drugs. The
      possibility of deleterious effects is important to consider when prescribing
      antiepileptic drug treatment.

PMID- 17018698
TI  - Preoperative estimation of residual volume for WHO grade II glioma resected with
      intraoperative functional mapping.
AB  - Despite the lack of class I evidence, it is widely agreed that surgery can
      improve the functional and vital prognosis for WHO grade II gliomas when the
      resection is at least subtotal radiologically, that is, leaving less than 10
      cm(3) of visible residual tumor. Because these tumors frequently invade
      functional areas, the preoperative estimation of the probable residual volume
      remains challenging. This article presents a probabilistic map of postoperative
      residues, with the aim of predicting before the decision for surgical
      intervention whether the resection could be subtotal. We selected 65 patients who
      underwent surgery with intraoperative functional mapping between 1999 and 2004
      for a WHO grade II glioma located in a sensorimotor and/or language area. For
      each case, the postoperative image was normalized on a standard atlas, and the
      residual tumor was segmented. A probabilistic map of residues was then computed.
      The fusion between the map and a preoperative image allowed a preoperative
      estimation of the expected extent of resection. The map enhances the regions
      where grade II glioma cannot be resected. The success rate for the preoperative
      classification of partial versus subtotal resection is 82%. Although both its
      reliability and accuracy have to be improved, this probabilistic map gives
      preoperatively an objective estimation of the expected extent of resection for
      grade II glioma resected under intraoperative functional mapping. This rationale
      will assist in decisions regarding surgical resection and may thus contribute to
      the elaboration of a therapeutic consensus for WHO grade II glioma.

PMID- 17018699
TI  - Levels and distribution of BCNU in GBM tumors following intratumoral injection of
      DTI-015 (BCNU-ethanol).
AB  - The alkylation products formed by in vitro treatment of DNA with tritium-labeled
      1,3-bis(2-chloroethyl)-1-nitrosourea ((3)H-BCNU) were identified and quantified.
      Twelve adducts were resolved by high-performance liquid chromatography (HPLC).
      The principal DNA adducts formed by BCNU treatment corresponded to N-7-(2
      hydroxyethyl)guanine (N7-HOEtG) (26%), N-7-(2-chloroethyl)guanine (15%), and
      phosphotriesters (19%). In addition, several minor products were identified as
      1,2-(diguan-7-yl)ethane, N-1-(2-hydroxyethyl)-2-deoxyguanosine, 1-(N-1-2
      deoxyguanosinyl), 2-(N-3-2-deoxycytidyl)ethane cross-link, and O-6-(2
      hydroxyethyl)-2-deoxyguanosine, and individually they represented 1% to 5% of the
      total alkylation. An HPLC-electrochemical method was applied to quantify the
      levels of N7-HOEtG in samples treated with BCNU. Treatment of either purified DNA
      or U87MG cells with various amounts of BCNU produced a linear increase in the
      amount of N7-HOEtG. These results demonstrated that the levels of N7-HOEtG formed
      by BCNU treatment could be used as a molecular dosimeter of BCNU treatment dose.
      We measured the levels of N7-HOEtG in DNA isolated from tumor samples taken from
      four patients with GBM tumors following stereotactic intratumoral injection with
      DTI-015 (BCNU-ethanol). The level of N7-HOEtG in these samples ranged from 14.7
      to 121.9 micromol N7-HOETG/mol DNA within 1 cm of the site of injection. As the
      distance from the site of injection increased, the levels of N7-HOEtG in tumor
      DNA decreased. In two of the samples, the levels of N7-HOEtG were 0.2 to 0.3
      micromol N7-HOETG/mol DNA at 3.5 to 3.9 cm from the site of injection,
      demonstrating significant distribution of BCNU in the tumor. The levels of N7
      HOEtG in these tumor samples corresponded to BCNU treatment concentrations of
      0.02 to 43.0 mM. These studies demonstrate that stereotactic intratumoral
      injection of DTI-015 into human GBM tumors produces high concentrations of BCNU
      up to 2.5 cm from the site of injection in some of the tumors. These observations
      suggest that intratumoral injection of DTI-015 may be of benefit in the treatment
      of primary and recurrent GBM tumors.

PMID- 17018700
TI  - Exposure to a nutrition supplementation intervention in early childhood and risk
      factors for cardiovascular disease in adulthood: evidence from Guatemala.
AB  - To study the role of nutrition in the association of birth size and childhood
      growth with development of cardiovascular disease, the authors in 2002-2004
      surveyed 665 men and 790 women aged 25-42 years who had been exposed as children
      to a community-randomized nutrition supplementation intervention in four villages
      in eastern Guatemala. Exposure was associated with a lower fasting glucose level
      (7.0 mg/dl, 95% confidence interval (CI): 0.5, 13.5) for exposure at ages 36-72
      months; lower systolic blood pressure (3.0 mmHg, 95% CI: 0.4, 5.6) for exposure
      at ages 24-60 months; and a lower triglyceride level (sex-adjusted; 22.2 mg/dl,
      95% CI: 0.4, 44.1) and higher high density lipoprotein cholesterol level (males
      only; 4.7 mg/dl, 95% CI: 1.5, 7.9) for exposure prior to age 36 months. Improved
      nutrition at any age prior to 7 years was not associated with diastolic blood
      pressure, total or low density lipoprotein cholesterol level, or prevalence of
      the metabolic syndrome. Interventions designed to address nutrient deficiencies
      and ameliorate stunting that are targeted at pregnant women and young children
      are unlikely to increase cardiovascular disease risk later in life and may
      instead lower the risk.

PMID- 17018701
TI  - Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease:
      a HuGE review.
AB  - This review examines the association of a subset of endothelial nitric oxide
      synthase gene (NOS3) polymorphisms (Glu298Asp, intron 4, and -786T>C) with
      cardiovascular disease. The Glu298Asp polymorphism within exon 7 is the only
      common nonsynonymous variant. The variants have been associated with low plasma
      nitric oxide concentrations and reduced vascular reactivity; difficulties in
      measuring those phenotypes means that their functional role remains unclear. A
      large meta-analysis of NOS3 polymorphisms in coronary heart disease revealed per
      allele odds ratios of 1.17 (95% confidence interval: 1.07, 1.28) for Glu298Asp,
      1.17 (95% confidence interval: 1.07, 1.28) for -786T>C, and 1.12 (95% confidence
      interval: 1.01, 1.24) for intron 4. However, there was evidence that small
      studies with more striking results could affect the associations of the Glu298Asp
      and -786T>C polymorphisms with coronary heart disease. Associations of NOS3
      polymorphisms with hypertension, preeclampsia, stroke, and diabetes remain
      uncertain. To date, no reliable gene-gene or gene-environmental interactions have
      been described. Use of these variants in predictive testing is unlikely to be
      useful, although the population attributable fraction could be substantial if the
      modest associations are causal. The need for large-scale genetic association
      studies using tagging polymorphisms is warranted to confirm or refute a role of
      the NOS3 gene in coronary heart disease.

PMID- 17018702
TI  - Long-term results of a prospective trial of mantle irradiation alone for early
      stage Hodgkin's disease.
AB  - BACKGROUND: To determine the long-term treatment outcome and late effects of
      mantle irradiation alone in selected patients with early-stage Hodgkin's disease.
      METHODS: Between 1988 and 2000, 87 patients with pathologic stage (Ann Arbor) I
      IIA or clinical stage IA Hodgkin's disease were entered on to a prospective trial
      of mantle irradiation alone. Patients with B symptoms, large mediastinal
      adenopathy, or subcarinal or hilar involvement were excluded. The median doses to
      the mantle field and mediastinum were 36 Gy (range 30.3-40) and 38.6 Gy (range
      30.6-44), respectively. The actuarial freedom from treatment failure (FFTF) and
      overall survival (OS) rates were calculated using the Kaplan-Meier technique.
      RESULTS: The median follow-up was 107 months (range 23-192). Thirteen of 87
      patients (15%) relapsed at a median of 30 months (range 5-62). The 5- and 10-year
      actuarial FFTF rates were 86% and 84.7%, respectively. All 13 patients who
      relapsed are alive without evidence of disease at a median of 84 months (range 30
      156) post-salvage therapy. Five patients developed a second malignancy at a
      median of 93 months (range 27-131). The 10-year actuarial risk of a second
      malignancy was 4.5%. There have been two deaths to date, both due to second
      malignancies. The 10-year OS rate was 98.2%. CONCLUSION: In selected patients
      with early-stage Hodgkin's disease, mantle irradiation alone has an excellent
      long-term survival rate, comparing favorably with the previous standard treatment
      of extended-field radiation therapy and the current standard of combined modality
      therapy.

PMID- 17018703
TI  - New agents for treatment of advanced transitional cell carcinoma.
AB  - The prognosis for any patient with progressive or recurrent invasive transitional
      cell carcinoma remains poor. In this context, the focus of clinical research in
      these invasive cancers concentrates on identifying systemic treatment options and
      new agents in order to improve survival of patients. Cisplatin-based chemotherapy
      is standard treatment of patients with metastatic urothelial cancer; however,
      despite regimens as the cisplatin-gemcitabine combination, the overall response
      rates vary between 40% and 65%, with complete response in 15%-25% with survivals
      up to 16 months. This survival is frequently achieved with severe and life
      threatening side effects. None the less, almost all responding patients relapse
      within the first year; therefore, the need for development of new and tolerable
      agents is urgent. This review highlights some new active chemotherapeutic as new
      platinum compounds (oxaliplatin, lobaplatin), gallium nitrate, ifosfamide, the
      antifolates piritrexim and pemetrexed (Alimta, LY231514), vinflunine and
      molecular targeting agents such as farnesyltransferase inhibitors (lonafarnib,
      R115777, SCH66336), ribozyme (RPI.4610), histone deacetylase inhibitor (CI-994)
      and monoclonal antibodies (epidermal growth factor receptor, Her 2/neu).

PMID- 17018704
TI  - Peripheral blood mononuclear and tumor cell pharmacodynamics of the novel
      epothilone B analogue, ixabepilone.
AB  - BACKGROUND: We previously demonstrated that peak microtubule bundle formation
      (MBF) in peripheral blood mononuclear cells (PBMCs) occurs at the end of drug
      infusion and correlates with drug pharmacokinetics (PK). In the current study, a
      new expanded evaluation of drug target effect was undertaken. PATIENTS AND
      METHODS: Patients with advanced solid malignancies were treated with ixabepilone
      40 mg/m2 administered as a 1-h i.v. infusion every 3 weeks. Blood, plasma, and
      tumor tissue sampling was carried out to characterize pharmacodynamics and PK.
      RESULTS: Forty-seven patients were treated with 141 cycles of ixabepilone. In
      both PBMCs (n=27) and tumor cells (n=9), peak MBF occurred at the end of
      infusion; however, at 24-72 h after drug infusion, the number of cells with MBF
      was significantly greater in tumor cells, relative to PBMCs. A Hill model
      (EC50=109.65 ng/ml; r2=0.94) was fitted, which demonstrated a relationship
      between percentage of PBMCs with MBF and plasma ixabepilone concentration. The
      percentage of PBMCs with MBF at the end of infusion also correlated with severity
      of neutropenia (P=0.050). CONCLUSIONS: Plasma ixabepilone concentration and
      severity of neutropenia correlate with the level of MBF in PBMCs. Therefore, this
      technically straightforward assay should be considered as a complement to the
      clinical development of novel microtubule-binding agents.

PMID- 17018705
TI  - A clinicopathological retrospective study of 131 patients with primary bone
      lymphoma: a population-based study of successively treated cohorts from the
      British Columbia Cancer Agency.
AB  - BACKGROUND: Primary bone lymphoma (PBL) is a distinct clinicopathological entity.
      Although PBL has been reviewed in several small studies, few reflect recent
      improvements in primary treatment. METHODS: We used the British Columbia Cancer
      Agency Lymphoid Cancer Database to identify all patients with PBL (1983-2005).
      All were staged in a uniform manner and treated with era-specific protocols.
      RESULTS: We identified 131 patients with a median age of 63 years (18-87). One
      third had disease in long bones and another one third had disease in the spine,
      of which half presented with spinal cord compression. Patients with diffuse large
      cell lymphoma (DLCL) (n=103, 79%) had 5- and 10-year overall survivals (OS) of
      62% and 41%, respectively. Multivariate analysis identified three prognostic
      groups: age<60 with International Prognostic Index (IPI) 1-3 (n=43), age>or=60
      with IPI 0-3 (n=23) and age>or=60 with IPI 4-5 (n=33), with markedly different 5
      year OS of 90%, 61% and 25%, respectively (P<0.0001). Neither primary site nor
      pathological fracture at presentation had an impact on OS. The 3-year progression
      free survival in patients who received rituximab plus combination chemotherapy
      with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOPR)
      chemotherapy was 88% compared with 52% in those who received CHOP-like
      chemotherapy without rituximab (P=0.005). The 10-year OS for those with advanced
      stage disease who received irradiation plus chemotherapy was 25% versus 56% for
      those who received chemotherapy alone (P=0.025). Patients received irradiation if
      spinal cord compression was present or residual disease at the end of
      chemotherapy was thought to require it. CONCLUSIONS: PBL is usually of DLCL type
      and has an improved outcome with CHOPR. Younger patients with good IPI score have
      a favorable prognosis.

PMID- 17018706
TI  - Fried foods, olive oil and colorectal cancer.
AB  - BACKGROUND: The epidemiologic evidence for an etiologic role of fried foods and
      heterocyclic amines in colorectal carcinogenesis is inconsistent. PATIENTS AND
      METHODS: We have investigated the relation between fried foods and colorectal
      cancer risk using data from a large, multicentric case-control study conducted in
      Italy and Switzerland between 1992 and 2000, with 1394 cases of colon cancer, 886
      cases of rectal cancer and 4765 controls. RESULTS: After allowing for major
      relevant covariates, the multivariate odds ratios (ORs) for an increment of one
      portion per week of fried foods were 0.97 [95% confidence interval (CI)=0.93
      1.01] for colon cancer and 1.04 (95% CI=1.00-1.09) for rectal cancer. When we
      analyzed the type of fats mainly used for frying, we found that olive oil, but
      not other types of oils, appeared to protect from colon cancer risk (OR=0.89, 95%
      CI=0.82-0.98). CONCLUSIONS: Our results do not indicate a relevant role of fried
      foods on colorectal cancer risk. We found a possible favorable effect of (fried)
      olive oil on colon cancer risk but not on rectal cancer risk.

PMID- 17018707
TI  - A systematic review of common conservative therapies for arm lymphoedema
      secondary to breast cancer treatment.
AB  - Secondary arm lymphoedema is a chronic and distressing condition which affects a
      significant number of women who undergo breast cancer treatment. A number of
      health professional and patient instigated conservative therapies have been
      developed to help with this condition, but their comparative benefits are not
      clearly known. This systematic review undertook a broad investigation of commonly
      instigated conservative therapies for secondary arm lymphoedema including;
      complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral
      pharmaceuticals, low level laser therapy, compression bandaging and garments,
      limb exercises and limb elevation. It was found that the more intensive and
      health professional based therapies, such as complex physical therapy, manual
      lymphatic drainage, pneumatic pump and laser therapy generally yielded the
      greater volume reductions, whilst self instigated therapies such as compression
      garment wear, exercises and limb elevation yielded smaller reductions. All
      conservative therapies produced improvements in subjective arm symptoms and
      quality of life issues, where these were measured. Despite the identified
      benefits, there is still the need for large scale, high level clinical trials in
      this area.

PMID- 17018708
TI  - Incidence and risk factors of central nervous system recurrence in aggressive
      lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade
      Non-Hodgkin's Lymphoma Study Group (DSHNHL).
AB  - BACKGROUND: Central nervous system (CNS) relapse is a devastating and usually
      fatal complication of aggressive lymphoma. The extent of the disease, the
      proliferation rate and the sites of extranodal involvement have been discussed as
      risk factors. We analyzed the patients treated on protocols of the German High
      Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) between 1990 and 2000,
      evaluated the rate and prognostic factors for CNS recurrence and developed a risk
      model trying to identify subsets of patients suitable for future prophylactic
      strategies. PATIENTS AND METHODS: From 1993 to 2000, 1399 patients [<or=60 years
      with normal lactate dehydrogenase (LDH) and >60 years irrespective of LDH] were
      randomized to receive six cycles of combination chemotherapy with
      cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-21, CHOP-14 or
      six cycles of CHOP+etoposide (CHOEP)-21, CHOEP-14 in a 2x2 factorial study design
      in the NHL-B1/B2 studies. From 1990 to 1997, 312 patients<or=60 years with an
      elevated LDH were randomized to five cycles CHOEP+involved field (IF)
      radiotherapy or three cycles CHOEP followed by high-dose BCNU, etoposide,
      cytarabine and melphalan (BEAM) and autologous stem-cell transplantation (NHL-A
      study). RESULTS: A total number of 1711 patients were initially eligible for this
      study, of whom 18 patients had to be excluded due to primary CNS involvement. In
      the remaining 1693 assessable patients, 37 cases of relapse or progression to the
      CNS (2.2%) were observed. The protocol asked for an intrathecal (i.th.)
      prophylaxis in patients with lymphoblastic lymphoma only (n=17), but overall 71
      patients (71 of 1693=4.2%) received prophylaxis by decision of the treating
      physicians. Multivariate Cox regression analysis identified increased LDH
      (P<0.001) and involvement of more than one extranodal site (P=0.002) as
      independent predictors of CNS recurrence in the NHL-B1/B2 study population.
      Treatment with etoposide also evolved as a prognostic factor because the risk of
      CNS failure was significantly reduced after CHOEP (P=0.017). Elderly patients
      presenting with both an elevated LDH and lymphoma involvement in liver, bladder
      or adrenals had an up to 15-fold risk of spread of the disease to the CNS.
      CONCLUSION: The incidence of CNS relapse in 1693 patients treated for aggressive
      lymphomas on DSHNHL protocols from 1990 to 2000 was low (2.2%), although CNS
      prophylaxis was administered to <5% of patients. Thus, a general prophylaxis for
      all patients is not warranted, the less so since the effectiveness of i.th.
      prophylaxis itself is judged controversially. Increased LDH and involvement of
      more than one extranodal site were confirmed as independent risk factors. A
      cumulative 20% incidence of CNS disease in certain prognostic subgroups of
      elderly patients may render these candidates for i.th. prophylaxis; however, this
      approach would imply a potential overtreatment of approximately 80% of these
      patients deemed at high risk.

PMID- 17018709
TI  - Expanding role of chemotherapy in lung cancer.

PMID- 17018710
TI  - The expanding role of systemic treatment in non-small cell lung cancer neo
      adjuvant therapy.

PMID- 17018711
TI  - The role of systemic therapy for localised gastric cancer.

PMID- 17018712
TI  - The integration of targeted agents into systemic therapy of metastatic colorectal
      cancer.

PMID- 17018714
TI  - Hematological malignancies: myeloma.

PMID- 17018713
TI  - A multimodality approach to localized rectal cancer.

PMID- 17018715
TI  - The biology and treatment of chronic lymphocytic leukemia.

PMID- 17018716
TI  - Current treatment strategies in follicular lymphomas.

PMID- 17018717
TI  - Diagnostic and therapeutic management of carcinoma of unknown primary:
      histopathological and molecular diagnosis.

PMID- 17018719
TI  - Treatment of patients with specific subsets of carcinoma of an unknown primary
      site.

PMID- 17018718
TI  - Diagnostic and therapeutic management of carcinoma of unknown primary: radio
      imaging investigations.

PMID- 17018720
TI  - Radiotherapy in malignant glioma.

PMID- 17018721
TI  - Adjuvant treatment of high grade gliomas.

PMID- 17018722
TI  - New horizons in the treatment of renal cell cancer.

PMID- 17018723
TI  - Brain tumors: molecular biology and targeted therapies.

PMID- 17018724
TI  - Biomarkers and screening for prostate cancer.

PMID- 17018725
TI  - Treatment of prostate cancer.

PMID- 17018726
TI  - Systemic treatment for prostate cancer.

PMID- 17018728
TI  - Concurrent chemoradiation for locally advanced carcinoma of the cervix: where are
      we in 2006?

PMID- 17018727
TI  - Cervical cancer and prevention by vaccination: results from recent trials.

PMID- 17018729
TI  - Muscle invasive and metastatic bladder cancer.

PMID- 17018731
TI  - The role of surgery in advanced and recurrent ovarian cancer.

PMID- 17018730
TI  - Cytotoxic chemotherapy for advanced or recurrent cervical cancer.

PMID- 17018732
TI  - Intraperitoneal chemotherapy in advanced ovarian cancer: recognition at last.

PMID- 17018733
TI  - New targets and non-cytotoxics in ovarian cancer.

PMID- 17018734
TI  - Proteomics in gastrointestinal cancer.

PMID- 17018735
TI  - Gene expression profiling in breast cancer.

PMID- 17018736
TI  - The impact of genomics and proteomics in the clinic: functional genetic
      polymorphisms and their value in response and toxicity prediction in solid
      tumours.

PMID- 17018737
TI  - Precancerous lesions of the breast.

PMID- 17018738
TI  - Chronic myelogenous leukemia (CML): resistance to tyrosine kinase inhibitors.

PMID- 17018739
TI  - Gastrointestinal stromal tumor (GIST).
AB  - Gastrointestinal stromal tumors (GISTs) may be defined as morphologically spindle
      cell, epithelioid, or occasionally pleomorphic mesenchymal tumours of the
      gastrointestinal tract that usually express the KIT protein and harbour mutation
      of a gene that encodes for a type III receptor tyrosine kinase (either KIT or
      PDGFRA). In Caucasian populations their annual incidence is 10 to 15 cases per
      million. Approximately 80% of GISTs have mutated KIT and 5% mutated PDGFRA. Most
      KIT mutations occur in untreated GISTs in the juxtamembrane exon 11 and only
      rarely in the kinase domain, whereas in imatinib-treated patients secondary
      mutations are frequent in exons encoding for the ATP/imatinib binding pocket or
      the kinase activation loop. Surgery is the standard treatment of local GIST.
      Tyrosine kinase inhibitor imatinib is the standard treatment for metastatic
      disease with few exceptions. A majority (80-90%) of patients with metastatic
      disease respond to imatinib or achieve durable tumour growth stabilisation with
      continuous therapy using a daily dose of 400 mg to 600 mg. Treatment with
      imatinib increases survival of patients with advanced disease with a few years
      and is associated with only moderate toxicity. Imatinib is being evaluated as
      adjuvant treatment following surgery, and other tyrosine kinase inhibitors as
      treatments of advanced GIST.

PMID- 17018740
TI  - Molecular imaging in oncology.

PMID- 17018741
TI  - Long-term outcome after adult-onset cancer.

PMID- 17018742
TI  - Palliative care: evaluation instruments in daily clinical practice.

PMID- 17018743
TI  - Nasopharyngeal carcinoma and therapeutic management: the place of chemotherapy.

PMID- 17018744
TI  - Medical treatments for hepatocellular carcinoma (HCC): what's next?

PMID- 17018745
TI  - Treatment of germ cell tumors--update 2006.

PMID- 17018747
TI  - MRI for breast cancer screening.

PMID- 17018746
TI  - Chemoresistance in solid tumours.

PMID- 17018748
TI  - Chemo-radiotherapy in head and neck cancer.

PMID- 17018749
TI  - Induction chemotherapy in head and neck cancer.

PMID- 17018750
TI  - Biological agents in head and neck cancer.

PMID- 17018751
TI  - Adjuvant treatment of breast cancer: sequence and duration of hormonal therapy.

PMID- 17018752
TI  - Adjuvant trastuzumab in early breast cancer.

PMID- 17018753
TI  - Meta-analyses of adjuvant therapies for women with early breast cancer: the Early
      Breast Cancer Trialists' Collaborative Group overview.

PMID- 17018754
TI  - Angiogenesis: health and disease.

PMID- 17018755
TI  - Targeting angiogenesis with oral agents.

PMID- 17018756
TI  - Targeting angiogenesis with monoclonal antibodies.

PMID- 17018757
TI  - Thrombosis and cancer.

PMID- 17018758
TI  - Neutropenia management.

PMID- 17018759
TI  - Daily challenges in oncology practice. What do we need to know about antiemetics?

PMID- 17018760
TI  - Non-small cell lung cancer: second-line and beyond.

PMID- 17018761
TI  - Abstracts of the 31st ESMO (European Society for Medical Oncology) Congress, 29
      September-3 October 2006, Istanbul, Turkey.

PMID- 17018765
TI  - Improving measurement in health education and health behavior research using item
      response modeling: introducing item response modeling.
AB  - This paper is the first of several papers designed to demonstrate how the
      application of item response models in the behavioral sciences can be used to
      enhance the conceptual and technical toolkit of researchers and developers and to
      understand better the psychometric properties of psychosocial measures. The
      papers all use baseline data from the Behavior Change Consortium data archive.
      This paper begins with an introduction to item response models, including both
      dichotomous and polytomous versions. The concepts of respondent and item
      location, model interpretation, standard errors and testing model fit are
      introduced and described. A sample analysis based on data from the self-efficacy
      scale is used to illustrate the concepts and techniques.

PMID- 17018766
TI  - Are schools a good setting for adolescent sexual health promotion in rural
      Africa? A qualitative assessment from Tanzania.
AB  - African adolescents are at high risk of poor sexual health. School-based
      interventions could reach many adolescents in a sustainable and replicable way,
      if enrolment, funding and infrastructure are adequate. This study examined
      pupils', recent school leavers', parents' and teachers' views and experiences of
      rural Tanzanian primary schools, focusing on the implications for potential
      sexual health programmes. From 1999 to 2002, participant observation was
      conducted in nine villages for 158 person-weeks. Half of Year 7 pupils were 15-17
      years old, and few went on to secondary school, suggesting that primary schools
      may be a good venue for such programmes. However, serious challenges include low
      enrolment and attendance rates, limited teacher training, little access to
      teaching resources and official and unofficial practices that may alienate pupils
      and their parents, e.g. corporal punishment, pupils being made to do unpaid work,
      forced pregnancy examinations, and some teachers' alcohol or sexual abuse. At a
      national level, improved teacher training and supervision are critical, as well
      as policies that better prevent, identify and correct undesired practices. At a
      programme level, intervention developers need to simplify the subject matter,
      introduce alternative teaching methods, help improve teacher-pupil and teacher
      community relationships, and closely supervise and appropriately respond to
      undesired practices.

PMID- 17018767
TI  - A process evaluation of a school-based adolescent sexual health intervention in
      rural Tanzania: the MEMA kwa Vijana programme.
AB  - This study is a process evaluation of the school component of the adolescent
      sexual health programme MEMA kwa Vijana (MkV), which was implemented in 62
      primary schools in rural Mwanza, Tanzania from 1999 to 2001. The MkV curriculum
      was a teacher-led and peer-assisted programme based on the Social Learning
      Theory. Process evaluation included observation of training sessions, monitoring
      and supervision, annual surveys of implementers, group discussions and 158 person
      weeks of participant observation. Most teachers taught curriculum content well,
      but sometimes had difficulty adopting new teaching styles. Peer educators
      performed scripted dramas well, but were limited as informal educators and
      behavioural models. The intervention appeared successful in addressing some
      cognitions, e.g. knowledge of risks and benefits of behaviours, but not others,
      e.g. perceived susceptibility to risk. MkV shared the characteristics of other
      African school-based programmes found to be successful, and similarly found
      significant improvements in self-reported behaviour in surveys. However, a
      substantial proportion of MkV survey self-reports were inconsistent, there was no
      consistent impact on biological markers and extensive process evaluation found
      little impact on several key theoretical determinants of behaviour. Improvements
      in self-reported survey data alone may provide only a very limited-and perhaps
      invalid-indication of adolescent sexual health programme success.

PMID- 17018768
TI  - Investing in the future--identifying participants in an educational program for
      middle-aged and older adults.
AB  - With the aging of societies, gerontological issues have become increasingly
      relevant. Within health education research, however, issues related to aging
      remain underrepresented. It is not yet understood whether and by what means
      people prepare for their aging. This article seeks to identify those who invest
      in the future by examining the reach of the educational program 'In anticipation
      of the golden years'. We studied what motivated participants to enroll, and
      collected demographic, psychological and social network characteristics from the
      158 individuals (mean age 61.5 years) who had signed up for the program. These
      data were compared with data from large-scale surveys of the aging population in
      order to examine the representativeness of program participants. The majority of
      participants' motives corresponded very well with the aims of the program.
      Comparison of demographic, psychological and social characteristics revealed
      that, in general, participants enjoyed greater psychological resources than in
      the population, while they were less advantaged with respect to their personal
      situation (predominantly household composition and subjective health) and social
      relationships. Our findings suggest that future investment in relation to aging
      is a well-accepted idea that appeals to individuals who exhibit a specific
      combination of resources and risk factors.

PMID- 17018769
TI  - Introducing multidimensional item response modeling in health behavior and health
      education research.
AB  - When measuring participant-reported attitudes and outcomes in the behavioral
      sciences, there are many instances when the common measurement assumption of
      unidimensionality does not hold. In these cases, the application of a
      multidimensional measurement model is both technically appropriate and
      potentially advantageous in substance. In this paper, we illustrate the
      usefulness of a multidimensional approach to measurement using an empirical
      example taken from the Behavior Change Consortium. Data from the Treatment Self
      Regulation Questionnaire have been analyzed to investigate whether self
      regulation can be regarded as a single construct, or if it has multiple
      dimensions based on the type of regulation or motivation that participants say
      helps them consider an improvement in healthy behavior. Comparison with
      consecutive analyses shows the advantages of multidimensional measurement for
      interpreting participant-reported data.

PMID- 17018770
TI  - Catching a 'hopeful monster': shepherd's purse (Capsella bursa-pastoris) as a
      model system to study the evolution of flower development.
AB  - Capsella is a small genus within the mustard family (Brassicaceae). Its three
      species, however, show many evolutionary trends also observed in other
      Brassicaceae (including Arabidopsis) and far beyond, including transitions from a
      diploid, self-incompatible, obligatory outcrossing species with comparatively
      large and attractive flowers but a restricted distribution to a polyploid, self
      compatible, predominantly selfing, invasive species with floral reductions. All
      these evolutionary transitions may have contributed to the fact that Capsella
      bursa-pastoris (shepherd's purse) has become one of the most widely distributed
      flowering plants on our planet. In addition, Capsella bursa-pastoris shows a
      phenomenon that, although rare, could be of great evolutionary importance,
      specifically the occurrence of a homeotic variety found in relatively stable
      populations in the wild. Several lines of evidence suggest that homeotic changes
      played a considerable role in floral evolution, but how floral homeotic varieties
      are established in natural populations has remained a highly controversial topic
      among evolutionary biologists. Due to its close relationship with the model plant
      Arabidopsis thaliana, numerous experimental tools are available for studying the
      genus Capsella, and further tools are currently being developed. Hence, Capsella
      provides great opportunities to investigate the evolution of flower development
      from molecular developmental genetics to field ecology and biogeography, and from
      morphological refinements to major structural transitions.

PMID- 17018771
TI  - Mitochondria play an important role in 17beta-estradiol attenuation of H(2)O(2)
      induced rat endothelial cell apoptosis.
AB  - Studies have shown salutary effects of 17beta-estradiol following trauma
      hemorrhage on different cell types. 17beta-Estradiol also induces improved
      circulation via relaxation of the aorta and has an anti-apoptotic effect on
      endothelial cells. Because mitochondria play a pivotal role in apoptosis, we
      hypothesized that 17beta-estradiol will maintain mitochondrial function and will
      have protective effects against H(2)O(2)-induced apoptosis in endothelial cells.
      Endothelial cells were isolated from rats' aorta and cultured in the presence or
      absence of H(2)O(2), a potent inducer of apoptosis. In additional studies,
      endothelial cells were pretreated with 17beta-estradiol. Flow cytometry analysis
      revealed H(2)O(2)-induced apoptosis in 80.9% of endothelial cells; however, prior
      treatment of endothelial cells with 17beta-estradiol resulted in an approximately
      40% reduction in apoptosis. This protective effect of 17beta-estradiol was
      abrogated when endothelial cells were cultured in the presence ICI-182780,
      indicating the involvement of estrogen receptor (ER). Fluorescence microscopy
      revealed a 17beta-estradiol-mediated attenuation of H(2)O(2)-induced
      mitochondrial condensation. Western blot analysis demonstrated that H(2)O(2)
      induced cytochrome c release from mitochondrion to cytosol and the activation of
      caspase-9 and -3 were decreased by 17beta-estradiol. These findings suggest that
      17beta-estradiol attenuated H(2)O(2)-induced apoptosis via ER-dependent
      activation of caspase-9 and -3 in rat endothelial cells through mitochondria.

PMID- 17018772
TI  - Expression of steroidogenic enzymes and synthesis of sex steroid hormones from
      DHEA in skeletal muscle of rats.
AB  - The functional importance of sex steroid hormones (testosterone and estrogens),
      derived from extragonadal tissues, has recently gained significant appreciation.
      Circulating dehydroepiandrosterone (DHEA) is peripherally taken up and converted
      to testosterone by 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD, and
      testosterone in turn is irreversibly converted to estrogens by aromatase
      cytochrome P-450 (P450arom). Although sex steroid hormones have been implicated
      in skeletal muscle regulation and adaptation, it is unclear whether skeletal
      muscles have a local steroidogenic enzymatic machinery capable of metabolizing
      circulating DHEA. Thus, here, we investigate whether the three key steroidogenic
      enzymes (3beta-HSD, 17beta-HSD, and P450arom) are present in the skeletal muscle
      and are capable of generating sex steroid hormones. Consistent with our
      hypothesis, the present study demonstrates mRNA and protein expression of these
      enzymes in the skeletal muscle cells of rats both in vivo and in culture (in
      vitro). Importantly, we also show an intracellular formation of testosterone and
      estradiol from DHEA or testosterone in cultured muscle cells in a dose-dependent
      manner. These findings are novel and important in that they provide the first
      evidence showing that skeletal muscles are capable of locally synthesizing sex
      steroid hormones from circulating DHEA or testosterone.

PMID- 17018773
TI  - Skeletal muscle fiber type comparison of pyruvate dehydrogenase phosphatase
      activity and isoform expression in fed and food-deprived rats.
AB  - Fiber type specificity of pyruvate dehydrogenase (PDH) phosphatase (PDP) was
      determined in fed (CON) and 48-h food-deprived (FD) rats. PDP activity and
      isoform protein content were determined in soleus (slow-twitch oxidative), red
      gastrocnemius (RG; fast-twitch oxidative glycolytic), and white gastrocnemius
      (WG; fast-twitch glycolytic) muscles. When normalized for mitochondrial volume,
      there was no difference in PDP activity between muscle types or CON and FD. When
      expressed per gram wet tissue weight, PDP activity was higher in RG compared with
      soleus and WG in both CON and FD rats. PDP activities from CON muscles were 1.48
      +/- 0.19, 2.68 +/- 0.65, and 1.20 +/- 0.33 nmol x min(-1) x g wet tissue wt(-1)
      in soleus, RG, and WG, respectively, and decreased in FD muscles (1.22 +/- 0.22,
      2.00 +/- 0.57, and 0.84 +/- 0.18 nmol x min(-1) x g wet tissue wt(-1)). This
      correlated with increased PDP2 protein, however, only in RG, as PDP2 was not
      detectable in soleus or WG. PDP1 protein was not responsive to food deprivation
      in all fiber types. In conclusion, PDP activity and protein content were higher
      in fast-twitch oxidative glycolytic muscles from CON and FD rats, identifying a
      unique inter- and intramuscular distribution. FD induced a small but significant
      decrease in PDP activity that was partially due to decreases in PDP2 protein. As
      a result, coordinate changes to PDP activity opposite to those of the other
      regulatory enzyme, PDH kinase, during food deprivation would maximize the
      inactivation of skeletal muscle PDH and enhance carbohydrate conservation during
      periods of limited carbohydrate supply.

PMID- 17018774
TI  - Can mutations in gamma-actin modulate the toxicity of microtubule targeting
      agents?

PMID- 17018775
TI  - Chlamydia or not Chlamydia, that is the question: which is the microorganism
      associated with MALT lymphomas of the ocular adnexa?

PMID- 17018776
TI  - Common genetic variants for breast cancer: 32 largely refuted candidates and
      larger prospects.

PMID- 17018777
TI  - FDA revamps committee conflict-of-interest rules.

PMID- 17018778
TI  - Decades after cancer, suicide risk remains high.

PMID- 17018779
TI  - Stat bite: Suicide circumstances, 2003-2004.

PMID- 17018780
TI  - New options expand possibilities for fertility preservation in cancer patients.

PMID- 17018781
TI  - Freezing embryos--a woman's best option, but is it legal?

PMID- 17018782
TI  - Surgeon General's report heralds turning tide against tobacco, smoking.

PMID- 17018783
TI  - Alterations in gamma-actin and tubulin-targeted drug resistance in childhood
      leukemia.
AB  - BACKGROUND: Proteomic investigations have revealed alterations in cytoskeletal
      proteins expressed in human acute lymphoblastic leukemia cells that are resistant
      to microtubule-disrupting agents. We characterized gamma-actin expression in
      antimicrotubule drug-resistant leukemia and examined the effect of altered gamma
      actin in resistance of acute lymphoblastic leukemia to antimicrotubule agents.
      METHODS: Two-dimensional polyacrylamide gel electrophoresis and mass spectrometry
      were used to identify actin proteins in human acute lymphoblastic leukemia cell
      lines resistant to vinblastine (CCRF-CEM/VLB100 cells) and desoxyepothilone B
      (CCRF-CEM/dEpoB140 cells). Fluorescence-based cycle sequencing was used to detect
      gene mutations. Site-directed mutagenesis was used to generate mutant gamma-actin
      expression plasmids, which were used to transfect mouse NIH/3T3 cells. Clonogenic
      analysis was used for drug sensitivity studies. A small interfering RNA (siRNA)
      was used to block gamma-actin gene expression in human neuroblastoma SH-EP cells.
      Expression of gamma-actin (normalized to that of beta2-microglobulin [beta2M]) in
      primary leukemia cells obtained from patients at diagnosis (n = 44) and relapse
      (n = 25) was examined using semiquantitative reverse transcription-polymerase
      chain reaction. Statistical significance of changes in the ratio of gamma-actin
      to beta2M expression between diagnosis and relapse samples was determined by two
      sided unpaired Student's t tests. RESULTS: We identified novel mutant forms of
      gamma-actin and the concomitant loss of wild-type gamma-actin in CCRF-CEM/VLB100
      cells and CCRF-CEM/dEpoB140 cells. Mouse NIH/3T3 cells that expressed the mutant
      gamma-actin proteins were more resistant to antimicrotubule agents than cells
      transfected with empty plasmid. Human neuroblastoma SH-EP cells transfected with
      gamma-actin siRNA displayed higher relative resistance to paclitaxel (P<.001),
      vinblastine (P = .04), and epothilone B (P = .045) than mock-transfected cells.
      No gamma-actin gene mutations were identified in 37 samples of primary leukemia
      cells (eight from patients at diagnosis, 29 from patients at relapse). Gamma
      actin gene expression was lower in acute lymphoblastic leukemia samples collected
      at clinical relapse (n = 25; mean gamma-actin/beta2M = 0.53) than in samples
      collected at diagnosis (n = 44; mean gamma-actin/beta2M = 0.68; difference =
      0.15, 95% confidence interval [CI] = 0.04 to 0.27, P = .01). CONCLUSIONS: These
      data provide functional and associative clinical evidence of a novel form of drug
      resistance that involves interactions between gamma-actin and microtubules.

PMID- 17018784
TI  - Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a
      multicenter prospective trial.
AB  - BACKGROUND: An association between ocular adnexal MALT lymphoma (OAL) and
      Chlamydia psittaci (Cp) infection has been proposed, and recent reports suggest
      that doxycycline treatment causes tumor regression in patients with Cp-related
      OAL. The effectiveness of doxycycline treatment in Cp-negative OAL has not been
      tested. METHODS: In a prospective trial, 27 OAL patients (15 newly diagnosed and
      12 having experienced relapse) were given a 3-week course of doxycycline therapy.
      Objective lymphoma response was assessed by computerized tomography scans or
      magnetic resonance imaging at 1, 3, and 6 months after the conclusion of therapy
      and every 6 months during follow-up. Cp infection in patients was determined by
      touchdown enzyme time-release polymerase chain reaction (TETR-PCR). Statistical
      tests were two-sided. RESULTS: Eleven patients were Cp DNA-positive and 16 were
      Cp DNA negative. Doxycycline was well tolerated. At a median follow-up of 14
      months, lymphoma regression was complete in six patients, and a partial response
      (> or = 50% reduction of all measurable lesions) was observed in seven patients
      (overall response rate [complete and partial responses] = 48%). Lymphoma
      regression was observed in both Cp DNA-positive patients (seven of 11 experienced
      regression) and Cp DNA-negative patients (six of 16 experienced regression) (64%
      versus 38%; P = .25, Fisher's exact test). The three patients with regional
      lymphadenopathies and three of the five patients with bilateral disease achieved
      objective response. In relapsed patients, response was observed both in
      previously irradiated and nonirradiated patients. The 2-year failure-free
      survival rate among the doxycycline-treated patients was 66% (95% confidence
      interval = 54 to 78), and 20 of the 27 patients were progression free.
      CONCLUSIONS: Doxycycline is a fast, safe, and active therapy for Cp DNA-positive
      OAL that was effective even in patients with multiple failures involving
      previously irradiated areas or regional lymphadenopathies. The responses observed
      in PCR-negative OAL may suggest a need for development of more sensitive methods
      for Cp detection and investigation of the potential role of other doxycycline
      sensitive bacteria.

PMID- 17018785
TI  - Commonly studied single-nucleotide polymorphisms and breast cancer: results from
      the Breast Cancer Association Consortium.
AB  - BACKGROUND: The Breast Cancer Association Consortium (BCAC) is an international
      collaboration that was established to provide large sample sizes for examining
      genetic associations. We conducted combined analyses on all single-nucleotide
      polymorphisms (SNPs) whose associations with breast cancer have been investigated
      by at least three participating groups. METHODS: Data from up to 12 studies were
      pooled for each SNP (ADH1C I350V, AURKA F31I, BRCA2 N372H, CASP8 D302H, ERCC2
      D312N, IGFBP3 -202 c>a, LIG4 D501D, PGR V660L, SOD2 V16A, TGFB1 L10P, TP53 R72P,
      XRCC1 R399Q, XRCC2 R188H, XRCC3 T241M, XRCC3 5' UTR, and XRCC3 IVS7-14). Genotype
      frequencies in case and control subjects were compared, and genotype-specific
      odds ratios for the risk of breast cancer in heterozygotes and homozygotes for
      the rare allele compared with homozygotes for the common allele were estimated
      with logistic regression. Statistical tests were two-sided. RESULTS: The total
      number of subjects for analysis of each SNP ranged from 12,013 to 31,595. For
      five SNPs--CASP8 D302H, IGFBP3 -202 c>a, PGR V660L, SOD2 V16A, and TGFB1 L10P-
      the associations with breast cancer were of borderline statistical significance
      (P = .016, .060, .047, .056, and .0088 respectively). The remaining 11 SNPs were
      not associated with breast cancer risk; genotype-specific odds ratios were close
      to unity. There was some evidence for between-study heterogeneity (P<.05) for
      four of the 11 SNPs (ADH1C I350V, ERCC2 D312N, XRCC1 R399Q, and XRCC3 IVS5-14).
      CONCLUSION: Pooling data within a large consortium has helped to clarify
      associations of SNPs with breast cancer. In the future, consortia such as the
      BCAC will be important in the analysis of rare polymorphisms and gene x gene or
      gene x environment interactions, for which individual studies have low power to
      identify associations, and in the validation of associations identified from
      genome-wide association studies.

PMID- 17018786
TI  - Menopausal hormone therapy and ovarian cancer risk in the National Institutes of
      Health-AARP Diet and Health Study Cohort.
AB  - BACKGROUND: Recent studies offer conflicting data on risks of ovarian cancer in
      users of menopausal hormone therapy. Some findings of increased risks associated
      with unopposed estrogen use are based on older studies of women with intact
      uteri, and small sample size and incomplete exposure information have limited the
      data on estrogen plus progestin associations. METHODS: The National Institutes of
      Health-AARP Diet and Health Study Cohort included 97,638 women aged 50-71 years
      at baseline who completed two questionnaires (1995-1996 and 1996-1997). We
      identified 214 incident ovarian cancers among these women through the year 2000
      using data from state cancer registries and mortality indexes. We estimated
      relative risks (RRs) of ovarian cancer for detailed hormone therapy exposures
      using multivariable proportional hazards regression models. All statistical tests
      were two-sided. RESULTS: Use of unopposed estrogen for fewer than 10 years was
      not associated with ovarian cancer. Compared with use of no hormone therapy, use
      of unopposed estrogen for 10 or more years was statistically significantly
      associated with ovarian cancer among all women (RR = 1.89, 95% confidence
      interval [CI] = 1.22 to 2.95; P = .004; 56 versus 72 ovarian cancers per 100,000
      person-years, respectively) and, albeit not statistically significantly, among
      women with hysterectomy (n = 19,359, RR = 1.70, 95% CI = 0.87 to 3.31; P = .06).
      Among the 73,483 women with intact uteri, 51,698 had used no hormone therapy or
      only estrogen plus progestin. Compared with no hormone therapy use, 5 or more
      years of use of sequential (progestin for < 15 days per cycle; RR = 3.09, 95% CI
      = 1.68 to 5.68; P < .001; 49 versus 108 per 100,000 person-years) or continuous
      (progestin for > or = 15 days per cycle; RR = 1.82, 95% CI = 1.03 to 3.23; P =
      .02; 49 versus 66 per 100,000 person-years) estrogen plus progestin regimens were
      statistically significantly associated with ovarian cancer. CONCLUSIONS: Long
      durations of use of unopposed estrogen and of estrogen plus progestin, especially
      sequential regimens, are associated with increased ovarian cancer risk. These
      data expand the range of possible risks associated with menopausal hormone
      therapy.

PMID- 17018787
TI  - Endogenous steroid hormone concentrations and risk of breast cancer among
      premenopausal women.
AB  - BACKGROUND: Higher levels of endogenous sex steroid hormones are associated with
      increased risks of breast cancer in postmenopausal women. Data for premenopausal
      women are sparse, in part because of the complexity of measuring hormone levels
      that vary cyclically. We prospectively evaluated associations between plasma sex
      hormone levels and breast cancer risk among premenopausal women in a case-control
      study nested within the Nurses' Health Study II. METHODS: From 1996 to 1999,
      blood samples were collected from 18,521 premenopausal women during the early
      follicular and midluteal phases of their menstrual cycles. A total of 197 cases
      of breast cancer were diagnosed among these women after blood collection and
      before June 1, 2003; these case subjects were matched to 394 control subjects.
      Logistic regression models, controlling for breast cancer risk factors, were used
      to calculate relative risks (RRs) and 95% confidence intervals (CIs). All
      statistical tests were two-sided. RESULTS: Women in the highest (versus the
      lowest) quartiles of follicular total and free estradiol levels had statistically
      significantly increased risks of breast cancer (RR = 2.1 [95% CI = 1.1 to 4.1],
      P(trend) = .08, and RR = 2.4 [95% CI = 1.3 to 4.5], P(trend) = .01,
      respectively); the associations were stronger for invasive breast cancer and for
      estrogen and progesterone receptor-positive (ER+/PR+) tumors. Luteal estradiol
      levels were not associated with breast cancer risk. Higher levels of total and
      free testosterone and androstenedione in both menstrual cycle phases were
      associated with modest, non-statistically significant increases in overall risk
      of breast cancer and with stronger, statistically significant increases in risks
      of invasive and ER+/PR+ cancers (e.g., RR of invasive cancers for the top [versus
      bottom] quartile of luteal total testosterone levels = 2.0 [95% CI = 1.1 to 3.6],
      P(trend) = .05, and RR of ER+/PR+ cancers = 2.9 [95% CI = 1.4 to 6.0], P(trend) =
      .02). Levels of estrone, estrone sulfate, progesterone, and sex hormone-binding
      globulin were not associated with breast cancer risk. The absolute number of
      cases observed over 3 years were 30 among women in the lowest 25% of follicular
      total estradiol levels and 50 among women in the highest 25%. CONCLUSIONS: Levels
      of circulating estrogens and androgens may be important in the etiology of
      premenopausal breast cancer.

PMID- 17018788
TI  - Suicide after breast cancer: an international population-based study of 723,810
      women.
AB  - Few studies have examined long-term suicide risk among breast cancer survivors,
      and there are no data for women in the United States. We quantified suicide risk
      through 2002 among 723,810 1-year breast cancer survivors diagnosed between
      January 1, 1953, and December 31, 2001, and reported to 16 population-based
      cancer registries in the United States and Scandinavia. Among breast cancer
      survivors, we calculated standardized mortality ratios (SMRs) and excess absolute
      risks (EARs) compared with the general population, and the probability of
      suicide. We used Poisson regression likelihood ratio tests to assess
      heterogeneity in SMRs; all statistical tests were two-sided, with a .05 cutoff
      for statistical significance. In total 836 breast cancer patients committed
      suicide (SMR = 1.37, 95% confidence interval [CI] = 1.28 to 1.47; EAR = 4.1 per
      100,000 person-years). Although SMRs ranged from 1.25 to 1.53 among registries,
      with 245 deaths among the sample of US women (SMR = 1.49, 95% CI = 1.32 to 1.70),
      differences among registries were not statistically significant (P for
      heterogeneity = .19). Risk was elevated throughout follow-up, including for 25 or
      more years after diagnosis (SMR = 1.35, 95% CI = 0.82 to 2.12), and was highest
      among black women (SMR = 2.88, 95% CI = 1.44 to 5.17) (P for heterogeneity =
      .06). Risk increased with increasing stage of breast cancer (P for heterogeneity
      = .08) and remained elevated among women diagnosed between 1990 and 2001 (SMR =
      1.36, 95% CI = 1.18 to 1.57). The cumulative probability of suicide was 0.20% 30
      years after breast cancer diagnosis.

PMID- 17018789
TI  - Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer
      following radical prostatectomy.
AB  - The risk of metastatic progression for prostate cancer patients who undergo
      radical prostatectomy is best estimated presently based on prostate-specific
      antigen (PSA) doubling time (PSADT). However, additional markers of risk are
      needed to identify patients who may benefit from aggressive salvage treatment. A
      decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate
      epithelium was previously shown to predict biochemical recurrence, as defined by
      rising levels of serum PSA after radical prostatectomy. We assessed the
      reliability with which AZPG1 expression could predict clinical recurrence and
      metastatic progression. Using immunohistochemical methods, we analyzed AZPG1
      expression in malignant prostate epithelium in prostatectomy specimens from 228
      prostate cancer patients. Low (i.e., absent or weak) AZGP1 expression was
      associated with clinical recurrence (defined as confirmed localized recurrence,
      metastasis, or death from prostate cancer; hazard ratio [HR] = 4.8, 95%
      confidence interval [CI] = 2.2 to 10.7, P<.001) and with bony metastases or death
      from prostate cancer (HR = 8.0, 95% CI = 2.6 to 24.3, P<.001). Among the 17
      patients in the cohort in whom clinical recurrence was associated with short
      PSADT, absent or weak AZGP1 expression was observed in 13 patients. If these
      preliminary findings are validated in independent cohorts, the measurement of
      AZGP1 levels in radical prostatectomy specimens may permit an accurate and timely
      assessment of risk of metastatic progression after radical prostatectomy.

PMID- 17018790
TI  - Re: Human papillomavirus infection and incidence of squamous cell and basal cell
      carcinomas of the skin.

PMID- 17018791
TI  - Re: Randomized double-blind factorial trial of three treatments to reduce the
      prevalence of precancerous gastric lesions.

PMID- 17018792
TI  - The cover. The Little Laundress.

PMID- 17018793
TI  - A piece of my mind. Patagonia pastorale.

PMID- 17018794
TI  - Scientists study fat as endocrine organ.

PMID- 17018795
TI  - Surgery useful for morbid obesity, but safety and efficacy questions linger.

PMID- 17018796
TI  - Better strategies sought against obesity.

PMID- 17018797
TI  - Fat and cholesterol regulator identified.

PMID- 17018798
TI  - Nanowires take on neuroscience.

PMID- 17018799
TI  - Shift shown in influenza A adamantane resistance.

PMID- 17018800
TI  - Shift shown in influenza A adamantane resistance.

PMID- 17018801
TI  - Credentialing, recertification, and public accountability.

PMID- 17018802
TI  - Clinical performance measures and medical malpractice.

PMID- 17018803
TI  - Drug safety monitoring.

PMID- 17018804
TI  - Trends in sudden cardiovascular death in young competitive athletes after
      implementation of a preparticipation screening program.
AB  - CONTEXT: A nationwide systematic preparticipation athletic screening was
      introduced in Italy in 1982. The impact of such a program on prevention of sudden
      cardiovascular death in the athlete remains to be determined. OBJECTIVE: To
      analyze trends in incidence rates and cardiovascular causes of sudden death in
      young competitive athletes in relation to preparticipation screening. DESIGN,
      SETTING, AND PARTICIPANTS: A population-based study of trends in sudden
      cardiovascular death in athletic and nonathletic populations aged 12 to 35 years
      in the Veneto region of Italy between 1979 and 2004. A parallel study examined
      trends in cardiovascular causes of disqualification from competitive sports in
      42,386 athletes undergoing preparticipation screening at the Center for Sports
      Medicine in Padua (22,312 in the early screening period [1982-1992] and 20,074 in
      the late screening period [1993-2004]). MAIN OUTCOME MEASURES: Incidence trends
      of total cardiovascular and cause-specific sudden death in screened athletes and
      unscreened nonathletes of the same age range over a 26-year period. RESULTS:
      During the study period, 55 sudden cardiovascular deaths occurred in screened
      athletes (1.9 deaths/100,000 person-years) and 265 sudden deaths in unscreened
      nonathletes (0.79 deaths/100,000 person-years). The annual incidence of sudden
      cardiovascular death in athletes decreased by 89% (from 3.6/100,000 person-years
      in 1979-1980 to 0.4/100,000 person-years in 2003-2004; P for trend < .001),
      whereas the incidence of sudden death among the unscreened nonathletic population
      did not change significantly. The mortality decline started after mandatory
      screening was implemented and persisted to the late screening period. Compared
      with the prescreening period (1979-1981), the relative risk of sudden
      cardiovascular death in athletes was 0.56 in the early screening period (95% CI,
      0.29-1.15; P = .04) and 0.21 in the late screening period (95% CI, 0.09-0.48; P =
      .001). Most of the reduced mortality was due to fewer cases of sudden death from
      cardiomyopathies (from 1.50/100,000 person-years in the prescreening period to
      0.15/100,000 person-years in the late screening period; P for trend = .002).
      During the study period, 879 athletes (2.0%) were disqualified from competition
      due to cardiovascular causes at the Center for Sports Medicine: 455 (2.0%) in the
      early screening period and 424 (2.1%) in the late screening period. The
      proportion of athletes who were disqualified for cardiomyopathies increased from
      20 (4.4%) of 455 in the early screening period to 40 (9.4%) of 424 in the late
      screening period (P = .005). CONCLUSIONS: The incidence of sudden cardiovascular
      death in young competitive athletes has substantially declined in the Veneto
      region of Italy since the introduction of a nationwide systematic screening.
      Mortality reduction was predominantly due to a lower incidence of sudden death
      from cardiomyopathies that paralleled the increasing identification of athletes
      with cardiomyopathies at preparticipation screening.

PMID- 17018805
TI  - Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study.
AB  - CONTEXT: Magnetic resonance imaging (MRI) findings have been reported for
      specific clinical cerebral palsy (CP) subgroups or lesion types but not in a
      large population of children with all CP subtypes. Further information about the
      causes of CP could help identify preventive strategies. OBJECTIVE: To investigate
      the correlates of CP in a population sample and compare clinical findings with
      information available from MRI brain studies. DESIGN AND SETTING: Cross
      sectional, population-based investigative study conducted in 8 European study
      centers (North West London and North East London, England; Edinburgh, Scotland;
      Lisbon, Portugal; Dublin, Ireland; Stockholm, Sweden; Tubingen, Germany; and
      Helsinki, Finland). PARTICIPANTS: Five hundred eighty-five children with CP were
      identified who had been born between 1996 and 1999; 431 children were clinically
      assessed and 351 had a brain MRI scan. MAIN OUTCOME MEASURES: Standardized
      clinical examination results, parental questionnaire responses, MRI results, and
      obstetric, genetic, and metabolic data from medical records. RESULTS: Important
      findings include the high rate of infections reported by mothers during pregnancy
      (n = 158 [39.5%]). In addition, 235 children (54%) were born at term while 47
      children (10.9%) were very preterm (<28 weeks). A high rate of twins was found,
      with 51 children (12%) known to be from a multiple pregnancy. Clinically, 26.2%
      of children had hemiplegia, 34.4% had diplegia, 18.6% had quadriplegia, 14.4% had
      dyskinesia, 3.9% had ataxia, and 2.6% had other types of CP. Brain MRI scans
      showed that white-matter damage of immaturity, including periventricular
      leukomalacia (PVL), was the most common finding (42.5%), followed by basal
      ganglia lesions (12.8%), cortical/subcortical lesions (9.4%), malformations
      (9.1%), focal infarcts (7.4%), and miscellaneous lesions (7.1%). Only 11.7% of
      these children had normal MRI findings. There were good correlations between the
      MRI and clinical findings. CONCLUSIONS: These MRI findings suggest that obstetric
      mishaps might have occurred in a small proportion of children with CP. A
      systematic approach to identifying and treating maternal infections needs to be
      developed. Multiple pregnancies should be monitored closely, and the causes of
      infant stroke need to be investigated further so preventive strategies can be
      formulated. All children with CP should have an MRI scan to provide information
      on the timing and extent of the lesion.

PMID- 17018806
TI  - Monoamine transporter gene polymorphisms and antidepressant response in koreans
      with late-life depression.
AB  - CONTEXT: Polymorphisms in the serotonin transporter gene (5-HTT) may influence
      antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The
      norepinephrine transporter (NET) is the analogous target for norepinephrine
      reuptake inhibitors (NRIs). OBJECTIVE: To determine whether antidepressant
      responses to SSRIs or NRIs are associated with genetic polymorphisms of the
      corresponding monoamine transporters. DESIGN, SETTING, AND PATIENTS: A 6-week
      naturalistic treatment study with blinded outcome evaluation of 241 Korean
      inpatients and outpatients with major depression at an academic psychiatry
      service. Patients were recruited to the study from March 1998 through February
      2003. INTERVENTIONS: Treatment with an SSRI (fluoxetine or sertraline; n = 136)
      or an NRI (nortriptyline; n = 105) antidepressant. Adherence was assessed by
      measuring plasma concentration at 4 weeks. Patients were genotyped for s/l
      polymorphisms in 5-HTT promoter region (5-HTTLPR), 5-HTT intron 2 s/l variation,
      and NET G1287A variation of exon 9. MAIN OUTCOME MEASURES: An SSRI and NRI
      response (defined as > or =50% decrease in Hamilton Rating Scale for Depression
      score at 6 weeks). RESULTS: NRI response was associated with the NET G1287A
      polymorphism (odds ratio [OR], 7.54; 95% confidence interval [CI], 2.53-22.49;
      P<.001). An SSRI response was associated with the 5-HTT intron 2 s/l variation
      (OR, 20.11; 95% CI, 4.27-94.74; P<.001). The 5-HTTLPR was also associated with an
      SSRI response (OR, 3.34; 95% CI, 1.41-7.91; P = .006). In contrast to studies in
      white patients, the favorable allele for SSRI response was S 5-HTTLPR. The S 5
      HTTLPR was associated also with NRI response (OR, 3.73; 95% CI, 1.32-10.53; P =
      .01). The NET polymorphism was not associated with an SSRI response. The NET
      G1287A GG genotype (56% of the population) was associated with better response to
      the NRI (83.3% [35/42]) than to SSRI (58.7% [44/75]) (OR, 3.52; 95% CI, 1.39
      8.95; P = .006). Some genotype combinations were associated with high rates of
      antidepressant response and others with low rates of response. CONCLUSIONS:
      Monoamine transporter gene polymorphisms were associated with response to
      antidepressants with homologous monoamine transporter targets. Combinations of
      polymorphisms were informative for response and nonresponse. Confirmation of
      these preliminary findings would permit refined pharmacogenetic selection of
      antidepressant treatment.

PMID- 17018807
TI  - Rapid response teams--walk, don't run.

PMID- 17018808
TI  - Protecting athletes from sudden cardiac death.

PMID- 17018809
TI  - Complexity of the cerebral palsy syndromes: toward a developmental neuroscience
      approach.

PMID- 17018810
TI  - JAMA patient page. Cerebral palsy.

PMID- 17018811
TI  - Human rights and ethics in public health.

PMID- 17018812
TI  - Jonathan Mann: founder of the health and human rights movement.

PMID- 17018813
TI  - On the application of decomposition methods.

PMID- 17018814
TI  - Blood and oil: vehicle characteristics in relation to fatality risk and fuel
      economy.
AB  - I examined the potential for a lower risk of death compatible with increased fuel
      economy among 67 models of 1999-2002 model year cars, vans, and sport-utility
      vehicles (SUVs) during the calendar years 2000 to 2004. The odds of death for
      drivers and all persons killed in vehicle collisions were related to vehicle
      weight, size, stability, and crashworthiness. I calculated that fatality rates
      would have been 28% lower and fuel use would have been reduced by 16% if vehicle
      weights had been reduced to the weight of vehicles with the lowest weight per
      size, where size is measured by the lateral distance needed to perform a 180
      degree turn. If, in addition, all vehicles had crashworthiness and stability
      equal to those of the top-rated vehicles, more than half the deaths involving
      passenger cars, vans, and SUVs could have been prevented by vehicle
      modifications.

PMID- 17018815
TI  - Ashkenazi Jews and breast cancer: the consequences of linking ethnic identity to
      genetic disease.
AB  - We explored the advantages and disadvantages of using ethnic categories in
      genetic research. With the discovery that certain breast cancer gene mutations
      appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved
      their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews
      as genetically unique, a legacy of Tay-Sachs disease research and a particular
      reading of history, shaped this new approach even as methodological imprecision
      and new genetic and historical research challenged it. Our findings cast doubt on
      the accuracy and desirability of linking ethnic groups to genetic disease. Such
      linkages exaggerate genetic differences among ethnic groups and lead to unequal
      access to testing and therapy.

PMID- 17018816
TI  - "It's like Tuskegee in reverse": a case study of ethical tensions in
      institutional review board review of community-based participatory research.
AB  - Community-based participatory research (CBPR) addresses the social justice
      dimensions of health disparities by engaging marginalized communities, building
      capacity for action, and encouraging more egalitarian relationships between
      researchers and communities. CBPR may challenge institutionalized academic
      practices and the understandings that inform institutional review board
      deliberations and, indirectly, prioritize particular kinds of research. We
      present our attempt to study, as part of a CBPR partnership, cigarette sales
      practices in an inner-city community. We use critical and communitarian
      perspectives to examine the implications of the refusal of the university
      institutional review board (in this case, the University of California, San
      Francisco) to approve the study. CBPR requires expanding ethical discourse beyond
      the procedural, principle-based approaches common in biomedical research
      settings. The current ethics culture of academia may sometimes serve to protect
      institutional power at the expense of community empowerment.

PMID- 17018817
TI  - Ethical conflicts in public health research and practice: antimicrobial
      resistance and the ethics of drug development.
AB  - Since the 1960s, scientists and pharmaceutical representatives have called for
      the advancement and development of new antimicrobial drugs to combat infectious
      diseases. In January 2005, Senate Majority Leader Bill Frist (R-TN), MD,
      introduced a biopreparedness bill that included provisions for patent extensions
      and tax incentives to stimulate industry research on new antimicrobials. Although
      government stimulus for private development of new antimicrobials is important,
      it does not resolve long-standing conflicts of interest between private entities
      and society. Rising rates of antimicrobial resistance have only exacerbated these
      conflicts. We used methicillin-resistant Staphylococcus aureus as a case study
      for reviewing these problems, and we have suggested alternative approaches that
      may halt the vicious cycle of resistance and obsolescence generated by the
      current model of antimicrobial production.

PMID- 17018818
TI  - Maternal upward socioeconomic mobility and black-white disparities in infant
      birthweight.
AB  - OBJECTIVES: We estimate the extent to which upward socioeconomic mobility limits
      the probability that Black and White women who spent their childhoods in or near
      poverty will give birth to a low-birthweight baby. METHODS: Data from the
      National Longitudinal Survey of Youth 1979 and the 1970 US Census were used to
      complete a series of logistic regression models. We restricted multivariate
      analyses to female survey respondents who, at 14 years of age, were living in
      households in which the income-to-needs ratio did not exceed 200% of poverty.
      RESULTS: For White women, the probability of giving birth to a low-birthweight
      baby decreases by 48% for every 1 unit increase in the natural logarithm of adult
      family income, once the effects of all other covariates are taken into account.
      For Black women, the relation between adult family income and the probability of
      low birthweight is also negative; however, this association fails to reach
      statistical significance. CONCLUSIONS: Upward socioeconomic mobility contributes
      to improved birth outcomes among infants born to White women who were poor as
      children, but the same does not hold true for their Black counterparts.

PMID- 17018819
TI  - Effectiveness of intensive case management for substance-dependent women
      receiving temporary assistance for needy families.
AB  - OBJECTIVE: We tested the effectiveness of a long-term coordinated care strategy-
      intensive case management (ICM)--compared with usual care (UC) among a group of
      substance-dependent women receiving Temporary Assistance for Needy Families
      (TANF). METHODS: Substance-dependent women on TANF (N=302) were recruited from
      welfare offices. They were assessed and randomly assigned to ICM or UC; follow-up
      was at 3, 9, and 15 months. UC consisted of a health assessment at the welfare
      office and a referral to substance abuse treatment and TANF services. ICM clients
      received ICM services in addition to UC services. RESULTS: ICM clients had
      significantly higher levels of substance abuse treatment initiation, engagement,
      and retention compared with UC clients. In some cases, ICM treatment attendance
      rates were double those of UC rates. Additionally, almost twice as many ICM
      clients were abstinent at the 15 month follow-up compared with UC clients
      (P<.0025). CONCLUSIONS: ICM is a promising intervention for managing the chronic
      nature of substance dependence among women receiving TANF. Future research should
      refine long-term care strategies-such as ICM-that address the chronic nature of
      substance dependence among low-income populations.

PMID- 17018820
TI  - Voluntary participation and informed consent to international genetic research.
AB  - OBJECTIVES: We compared voluntary participation and comprehension of informed
      consent among individuals of African ancestry enrolled in similarly designed
      genetic studies of hypertension in the United States and Nigeria. METHODS: Survey
      questionnaires were used to evaluate factors associated with voluntariness (the
      number of people volunteering) and understanding of the study's genetic purpose.
      A total of 655 individuals (United States: 348; Nigeria: 307) were interviewed
      after participation in the genetic studies. RESULTS: Most US respondents (99%),
      compared with 72% of Nigerian respondents, reported being told the study purpose.
      Fewer than half of the respondents at both sites reported that the study purpose
      was to learn about genetic inheritance of hypertension. Most respondents
      indicated that their participation was voluntary. In the United States, 97%
      reported that they could withdraw, compared with 67% in Nigeria. In Nigeria,
      nearly half the married women reported asking permission from husbands to enroll
      in the hypertension study; no respondents sought permission from local elders to
      participate in the study. CONCLUSIONS: Our findings highlight the need for more
      effective approaches and interventions to improve comprehension of consent for
      genetic research among ethnically and linguistically diverse populations in all
      settings.

PMID- 17018821
TI  - Public health implications of smokeless tobacco use as a harm reduction strategy.
AB  - Harm reduction strategies involve promoting a product that has adverse health
      consequences as a substitute for one that has more severe adverse health
      consequences. Smokeless tobacco low in nitrosamine content offers potential
      benefits in reducing smoking prevalence rates. Possible harm arises from the
      potential for such products to serve as a gateway to more harmful tobacco
      products, public misinterpretation of "less harmful" as "safe," distraction from
      the public health goal of tobacco elimination, and ethical issues involved in
      advising those marketing these harmful products. We offer a research agenda to
      provide a stronger basis for evaluating the risks and benefits of smokeless
      tobacco as a means of reducing the adverse health effects of tobacco.

PMID- 17018822
TI  - Investments in cancer genomics: who benefits and who decides.
AB  - The Cancer Genome Atlas--formerly the Human Cancer Genome Project--provides an
      opportunity for considering how social concerns about resource allocation are
      interrelated with practical decisions about specific research strategies--part of
      a continuing convergence between scientific and public evaluations of priorities
      for biomedical research funding. For example, the manner, order, and extent that
      The Cancer Genome Atlas selects tumor types and populations to be sampled will
      determine who benefits most from its findings. Those choices will be determined
      on the basis of both scientific and social values. By soliciting public
      involvement and conducting rigorous policy analysis in the design of large
      scientific projects such as The Cancer Genome Atlas, cancer researchers can help
      democratize the allocation of scientific resources and foster public confidence
      in biomedical research.

PMID- 17018823
TI  - Making big tobacco give in: you lose, they win.
AB  - OBJECTIVES: To better understand how the tobacco industry responds to tobacco
      control activists, we explored Philip Morris's response to demands that consumers
      in developing countries be informed about smoking risks, and analyzed the
      implications of negotiating with a tobacco company. METHODS: We reviewed internal
      tobacco industry documents and related materials, constructed a case history of
      how Philip Morris responded to a shareholder campaign to require health warnings
      on cigarettes sold worldwide, and analyzed interactions between (1) socially
      responsible investment activists, (2) Philip Morris management, (3) institutional
      investors, and (4) industry competitors. RESULTS: After resisting for 11 years,
      Philip Morris unilaterally reversed direction, and proposed its own labeling
      initiative. While activists celebrated, Philip Morris's president detailed
      privately how the company would yield little and benefit disproportionately.
      Activists portrayed the tobacco industry as preying on the poor and uneducated
      and used delegitimization to drive a wedge between the industry and its financial
      and political allies. When Philip Morris "gave in" to their demands, it exchanged
      negative publicity for positive public relations and political credibility.
      CONCLUSIONS: Tobacco companies can appear to accommodate public health demands
      while securing strategic advantages. Negotiating with the tobacco industry can
      enhance its legitimacy and facilitate its ability to market deadly cigarettes
      without corresponding benefits to public health.

PMID- 17018824
TI  - Safety belt use and the switch to primary enforcement, 1991-2003.
AB  - State seat belt laws have increased use rates and have reduced traffic
      fatalities, but tremendous variation exists in the laws. New Hampshire does not
      have a law, and 30 states have only secondary enforcement laws. Whereas primary
      enforcement allows an officer to issue a citation for any infraction, secondary
      enforcement permits a citation only if a motorist is stopped for another
      infraction first. We performed a cross-sectional time-series analysis of the
      impact of upgrading to primary enforcement on belt use rates for 47 states and
      the District of Columbia from 1991 to 2003. Our results suggest that states with
      secondary enforcement laws could increase belt use by 10 percentage points and
      improve public safety considerably by upgrading to primary enforcement.

PMID- 17018825
TI  - Transmission network analysis to complement routine tuberculosis contact
      investigations.
AB  - OBJECTIVE: We examined the feasibility and value of network analysis to
      complement routine tuberculosis (TB) contact investigation procedures during an
      outbreak. METHODS: We reviewed hospital, health department, and jail records and
      interviewed TB patients. Mycobacterium tuberculosis isolates were genotyped. We
      evaluated contacts of TB patients for latent TB infection (LTBI) and TB, and
      analyzed routine contact investigation data, including tuberculin skin test (TST)
      results. Outcomes included number of contacts identified, number of contacts
      evaluated, and their TST status. We used network analysis visualizations and
      metrics (reach, degree, betweenness) to characterize the outbreak. RESULTS:
      secondary TB patients and more than 1200 contacts. Genotyping detected a 21-band
      pattern of a strain W variant. No HIV-infected patients were diagnosed. Contacts
      prioritized by network analysis were more likely to have LTBI than nonprioritized
      contacts (odds ratio=7.8; 95% confidence interval=1.6, 36.6). Network
      visualizations and metrics highlighted patients central to sustaining the
      outbreak and helped prioritize contacts for evaluation. CONCLUSIONS: A network
      informed approach to TB contact investigations provided a novel means to examine
      large quantities of data and helped focus TB control.

PMID- 17018826
TI  - Exploring the ethics of clinical research in an urban community.
AB  - OBJECTIVES: We consulted with representatives of an urban community in
      Washington, DC, about the ethics of clinical research involving residents of the
      community with limited access to health care. METHODS: A semistructured community
      consultation was conducted with core members of the Health Partnership Program of
      the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three
      research case examples were discussed; questions and probes (a predetermined
      question or series of questions used to further investigate or follow-up a
      response) guided the discussion. RESULTS: The community representatives who took
      part in the consultation were supportive of research and appreciated the
      opportunity to be heard. They noted the importance of respecting the
      circumstances, values, needs, and welfare of research participants; supported
      widely representative recruitment strategies; and cited the positive benefits of
      providing care or treatment to participants. Monitoring participants' welfare and
      ensuring care at a study's end were emphasized. Trust was a central theme;
      participants suggested several trust-enhancing strategies, including full
      disclosure of information and the involvement of advocates, physicians, and
      trusted church members. CONCLUSIONS: Several important strategies emerged for
      conducting ethical research in urban communities whose residents have limited
      access to health care.

PMID- 17018827
TI  - Effects of sex work on the prevalence of syphilis among injection drug users in 3
      Russian cities.
AB  - OBJECTIVES: We examined risk factors for syphilis infection among injection drug
      users in 3 Russian Federation cities, focusing particular attention on the
      potential roles of gender and sex work. METHODS: We conducted a cross-sectional
      survey of injection drug users in Moscow, Volgograd, and Barnaul, collecting
      behavioral data and testing for antibodies to Treponema pallidum. Associations
      between presence of antibodies to T pallidum and covariates were explored.
      RESULTS: Overall, the prevalence of antibodies to T pallidum was 11% (95%
      confidence interval=9.7%, 13.1%). Syphilis was associated with involvement in sex
      work and with gender in Moscow and Barnaul but not in Volgograd. Female injection
      drug users not involved in sex work were more likely than men to be younger and
      to have recently begun to inject; female injection drug users involved in sex
      work were more likely than those not involved in sex work to inject daily.
      CONCLUSIONS: Syphilis transmission dynamics varied by region. Sex work can
      increase syphilis risk among injection drug users, potentially feeding the
      momentum of sexually transmitted HIV and syphilis among noninjectors. Targeted
      interventions are needed to reduce both sexual and injection risk behaviors among
      injection drug users.

PMID- 17018828
TI  - Privacy protection versus cluster detection in spatial epidemiology.
AB  - OBJECTIVES: Patient data that includes precise locations can reveal patients'
      identities, whereas data aggregated into administrative regions may preserve
      privacy and confidentiality. We investigated the effect of varying degrees of
      address precision (exact latitude and longitude vs the center points of zip code
      or census tracts) on detection of spatial clusters of cases. METHODS: We
      simulated disease outbreaks by adding supplementary spatially clustered emergency
      department visits to authentic hospital emergency department syndromic
      surveillance data. We identified clusters with a spatial scan statistic and
      evaluated detection rate and accuracy. RESULTS: More clusters were identified,
      and clusters were more accurately detected, when exact locations were used. That
      is, these clusters contained at least half of the simulated points and involved
      few additional emergency department visits. These results were especially
      apparent when the synthetic clustered points crossed administrative boundaries
      and fell into multiple zip code or census tracts. CONCLUSIONS: The spatial
      cluster detection algorithm performed better when addresses were analyzed as
      exact locations than when they were analyzed as center points of zip code or
      census tracts, particularly when the clustered points crossed administrative
      boundaries. Use of precise addresses offers improved performance, but this
      practice must be weighed against privacy concerns in the establishment of public
      health data exchange policies.

PMID- 17018829
TI  - Public willingness to participate in and public opinions about genetic variation
      research: a review of the literature.
AB  - Scientists are turning to genetic variation research in hopes of addressing
      persistent racial/ethnic disparities in health. Despite ongoing controversy, the
      advancement of genetic variation research is likely to produce new knowledge and
      technologies that will substantially change the ways in which we understand and
      value health. They also may affect the ways in which individuals and groups
      organize socially, politically, and economically. Addressing concerns that may
      exist in different communities is vital to the scientific and ethical advancement
      of genetic variation research. We review empirical studies of public willingness
      to participate in and opinions about genetic research with particular attention
      to differences in consent and opinion by racial/ethnic group membership.

PMID- 17018830
TI  - Effectiveness of bans and laws in reducing traffic deaths: legalized Sunday
      packaged alcohol sales and alcohol-related traffic crashes and crash fatalities
      in New Mexico.
AB  - We determined the relative risk of alcohol-related motor vehicle accidents and
      fatalities after New Mexico lifted its ban on Sunday packaged alcohol sales. We
      extracted all alcohol-related crashes from New Mexico police reports for 3652
      days between July 1, 1990, and June 30, 2000, and found a 29% increase in alcohol
      related crashes and a 42% increase in alcohol-related crash fatalities on Sundays
      after the ban on Sunday packaged alcohol sales was lifted. There was an estimated
      excess of 543.1 alcohol-related crashes and 41.6 alcohol-related crash fatalities
      on Sundays after the ban was lifted. Repealing the ban on Sunday packaged alcohol
      sales introduced a public health and safety hazard in New Mexico.

PMID- 17018831
TI  - Genes, race, and population: avoiding a collision of categories.
AB  - A wide array of federal mandates have a profound impact on the use of racial and
      ethnic categories in biomedical research, clinical practice, product development,
      and health policy. Current discussions over the appropriate use of racial and
      ethnic categories in biomedical contexts have largely focused on the practices of
      individual researchers. By contrast, our discussion focuses on relations between
      the daily practices of biomedical professionals and federal regulatory mandates.
      It draws upon the legal doctrine of equal protection to move beyond such debates
      and to propose guidelines to address the structural forces imposed by federal
      regulations that mandate how data about race and ethnicity are used in biomedical
      research. It offers a framework to manage the tension involved in using existing
      federally mandated categories of race and ethnicity alongside new scientific
      findings about human genetic variation.

PMID- 17018832
TI  - Dangerous journey: documenting the experience of Tibetan refugees.
AB  - OBJECTIVES: Since the 1950 invasion of Tibet by China, Tibetan refugees have
      attempted to flee into Nepal over the Himalayan mountains. We documented the
      experiences of a group of refugees making this journey. METHODS: We conducted
      semistructured interviews with 50 recent refugees at the Tibetan Refugee Transit
      Centre in Kathmandu, Nepal. RESULTS: Participants ranged in age from 8 to 56
      years, and 21 were female. The average length of their journey from Tibet to
      Nepal was 34 days. During their journey, a majority of the refugees encountered
      authorities or became involved in altercations with Nepali Maoist groups. Most of
      these interactions resulted in extortion and threats of expulsion. Several
      Tibetans were tortured, beaten with weapons, threatened with being shot, and
      robbed. Three women were sexually assaulted at gunpoint. CONCLUSIONS: The
      refugees who took part in this study experienced physical and mental hardships
      and, often, human rights abuses on their journey to Nepal. International pressure
      is needed to prevent human rights violations and reduce potential long-term
      physical and mental health effects associated with this dangerous crossing.

PMID- 17018833
TI  - Population-level changes in folate intake by age, gender, and race/ethnicity
      after folic acid fortification.
AB  - OBJECTIVES: We sought to quantify the impact of the 1998 US Food and Drug
      Administration (FDA) folic acid fortification policy by estimating folate intake
      at the population level. METHODS: We analyzed total folate intake levels (from
      food and supplements) according to gender, age, and race/ethnicity, using data
      from 2 National Health and Nutrition Examination Surveys. We measured pre- and
      postfortification folate intake distributions, adjusted for measurement error,
      and examined proportions of the population who reached certain thresholds of
      daily total folate intake. RESULTS: Mean daily food and total folate intake
      increased by approximately 100 microg/day after fortification. The proportion of
      women aged 15-44 years who consume more than 400 microg/day of folate has
      increased since fortification, but has not yet reached the FDA's 50% target and
      varies by race/ethnicity from 23% to 33%. Among persons aged 65 years and older
      who may be at risk for masking a vita-microg/day (the min B12 deficiency, the
      percentage who consume more than 1000 "tolerable upper intake level") has at
      least doubled among Whites and Black men, but has remained less than 5% for all
      groups. CONCLUSIONS: Since fortification, folic acid intake among the US
      population has increased, and there are substantial variations by age, gender,
      and race/ethnicity.

PMID- 17018834
TI  - An exploration of the dimensions of pregnancy intentions among women choosing to
      terminate pregnancy or to initiate prenatal care in New Orleans, Louisiana.
AB  - OBJECTIVES: We examined pregnancy decisionmaking among women seeking abortion or
      prenatal care. METHODS: Conventional measures of pregnancy intentions were
      compared with newer measures in 1017 women seeking abortion. A reduced sample of
      abortion patients (142 African American women from New Orleans) was compared with
      464 similar women entering prenatal care. RESULTS: Virtually all abortion
      patients reported the pregnancy as unintended; two thirds of prenatal patients
      reported the pregnancy as unintended. Reasons for seeking abortion related to
      life circumstances, including cost, readiness, not wanting any more children,
      marital status, relationship stability, and being too young. Abortion patients
      were more likely to report trying hard to avoid a pregnancy and not being in a
      relationship. They were less likely to report that their partner wanted a baby
      (odds ratio=0.10) or that they wanted a baby with their partner (odds ratio=0.13)
      than prenatal patients. CONCLUSIONS: Traditional measures of pregnancy intentions
      did not readily predict a woman's choice to continue or abort the pregnancy.
      Relationship with male partners, desire for a baby with the partner, and life
      circumstances were critical dimensions in pregnancy decisionmaking.

PMID- 17018835
TI  - Agent-based modeling of drinking behavior: a preliminary model and potential
      applications to theory and practice.
AB  - OBJECTIVES: We developed a preliminary agent-based simulation model designed to
      examine agent-environment interactions that support the development and
      maintenance of drinking behavior at the population level. METHODS: The model was
      defined on a 1-dimensional lattice along which agents might move left or right in
      single steps at each iteration. Agents could exchange information about their
      drinking with each other. In the second generation of the model, a "bar" was
      added to the lattice to attract drinkers. RESULTS: The model showed that changes
      in drinking status propagated through the agent population as a function of
      probabilities of conversion, rates of contact, and contact time. There was a
      critical speed of population mixing beyond which the conversion rate of
      susceptible nondrinkers was saturated, and the bar both enhanced and buffered the
      rate of propagation, changing the model dynamics. CONCLUSIONS: The models
      demonstrate that the basic dynamics underlying social influences on drinking
      behavior are shaped by contacts between drinkers and focused by characteristics
      of drinking environments.

PMID- 17018836
TI  - Welfare receipt and substance-abuse treatment among low-income mothers: the
      impact of welfare reform.
AB  - OBJECTIVES: We explored changing relations between substance use, welfare
      receipt, and substance-abuse treatment among low-income mothers before and after
      welfare reform. METHODS: We examined annual data from mothers aged 18 to 49 years
      in the 1990-2001 National Household Survey of Drug Abuse and the 2002 National
      Survey of Drug Use and Health. Logistic regression was used to examine
      determinants of treatment receipt. RESULTS: Among low-income, substance-using
      mothers, the proportion receiving cash assistance declined from 54% in 1996 to
      38% in 2001. The decline was much smaller (37% to 31%) among low-income mothers
      who did not use illicit substances. Low-income, substance-using mothers who
      received cash assistance were much more likely than other low-income, substance
      using mothers to receive treatment services. Among 2002 National Survey of Drug
      Use and Health respondents deemed "in need" of substance-abuse treatment, welfare
      recipients were significantly more likely than nonrecipients to receive such
      services (adjusted odds ratio=2.31; P<.05). Controlling for other factors,
      welfare receipt was associated with higher prevalence of illicit drug use. Such
      use declined among both welfare recipients and other mothers between 1990 and
      2001. CONCLUSIONS: Welfare is a major access point to identify and serve low
      income mothers with substance-use disorders, but it reaches a smaller proportion
      of illicit drug users than it did prereform. Declining welfare receipt among low
      income mothers with substance abuse disorders poses a new challenge in serving
      this population.

PMID- 17018837
TI  - Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators,
      energy homeostasis, and metabolism.
AB  - Many biological programs are regulated at the transcriptional level. This is
      generally achieved by the concerted actions of several transcription factors.
      Recent findings have shown that, in many cases, transcriptional coactivators
      coordinate the overall regulation of the biological programs. One of the best
      studied examples of coactivator control of metabolic pathways is the peroxisome
      proliferator-activated receptor coactivator 1 (PGC-1) family. These proteins are
      strong activators of mitochondrial function and are thus dominant regulators of
      oxidative metabolism in a variety of tissues. The PGC-1 coactivators themselves
      are subject to powerful regulation at the transcriptional and posttranslational
      levels. Recent studies have elucidated the function of the PGC-1 coactivators in
      different tissues and have highlighted the implications of PGC-1 dysregulation in
      diseases such as diabetes, obesity, cardiomyopathy, or neurodegeneration.

PMID- 17018838
TI  - The genetic landscape of type 2 diabetes in mice.
AB  - Inbred mouse strains provide genetic diversity comparable to that of the human
      population. Like humans, mice have a wide range of diabetes-related phenotypes.
      The inbred mouse strains differ in the response of their critical physiological
      functions, such as insulin sensitivity, insulin secretion, beta-cell
      proliferation and survival, and fuel partitioning, to diet and obesity. Most of
      the critical genes underlying these differences have not been identified,
      although many loci have been mapped. The dramatic improvements in genomic and
      bioinformatics resources are accelerating the pace of gene discovery. This review
      describes how mouse genetics can be used to discover diabetes-related genes,
      summarizes how the mouse strains differ in their diabetes-related phenotypes, and
      describes several examples of how loci identified in the mouse may directly
      relate to human diabetes.

PMID- 17018839
TI  - Membrane-initiated actions of estrogens in neuroendocrinology: emerging
      principles.
AB  - Hormonal ligands for the nuclear receptor superfamily have at least two
      interacting mechanisms of action: 1) classical transcriptional regulation of
      target genes (genomic mechanisms); and 2) nongenomic actions that are initiated
      at the cell membrane, which could impact transcription. Although transcriptional
      mechanisms are increasingly well understood, membrane-initiated actions of these
      ligands are incompletely understood. Historically, this has led to a considerable
      divergence of thought in the molecular endocrine field. We have attempted to
      uncover principles of hormone action that are relevant to membrane-initiated
      actions of estrogens. There is evidence that the membrane-limited actions of
      hormones, particularly estrogens, involve the rapid activation of kinases and the
      release of calcium. Membrane actions of estrogens, which activate these rapid
      signaling cascades, can also potentiate nuclear transcription. These signaling
      cascades may occur in parallel or in series but subsequently converge at the
      level of modification of transcriptionally relevant molecules such as nuclear
      receptors and/or coactivators. In addition, other hormones or neurotransmitters
      may also activate cascades to crosstalk with estrogen receptor-mediated
      transcription. The idea of synergistic coupling between membrane-initiated and
      genomic actions of hormones fundamentally revises the paradigms of cell signaling
      in neuroendocrinology.

PMID- 17018840
TI  - Membrane localization and pH-dependent transport of a newly cloned organic cation
      transporter (PMAT) in kidney cells.
AB  - Plasma membrane monoamine transporter (PMAT) is a novel membrane transporter
      recently cloned and characterized in our laboratory. We previously demonstrated
      that PMAT functions as a polyspecific organic cation transporter and efficiently
      transports many organic cations such as monoamine neurotransmitters and 1-methyl
      4-phenylpyridinium (MPP(+)). In this study, we explored the role of PMAT in the
      renal handling of organic cations. Using a polyclonal antibody generated toward
      the NH(2)-terminal 66 amino acid residues of human PMAT, we showed that the PMAT
      protein (approximately 55 kDa) is expressed in the human kidney and is primarily
      targeted to the apical membranes when expressed in polarized Madin-Darby canine
      kidney (MDCK) cells. Using MDCK cells stably expressing human PMAT, we showed
      that PMAT-mediated MPP(+) uptake is strongly dependent on extracellular pH.
      Lowering extracellular pH from 7.4 to 6.6 greatly stimulated PMAT-mediated MPP(+)
      uptake, whereas elevating extracellular pH to 8.2 abolished transporter activity.
      Kinetic analysis revealed that the apparent V(max) at pH 6.6 is about fourfold
      higher than that at pH 7.4, whereas the apparent K(m) values were not
      statistically different at these two conditions. Under acidic conditions (pH
      6.6), the proton ionophore, carbonyl cyanide p-trifluormethoxyphenylhydrazone,
      drastically reduced PMAT-mediated MPP(+) uptake, suggesting that the stimulatory
      effect of proton may be due to transporter coupling with a proton gradient. Taken
      together, our data suggest that PMAT is expressed on the apical membranes of
      renal epithelial cells and may use luminal proton gradient to drive organic
      cation reabsorption in the kidney.

PMID- 17018841
TI  - A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy.
AB  - We tested the hypothesis that AMP-activated protein kinase (AMPK), an energy
      sensor, regulates diabetes-induced renal hypertrophy. In kidney glomerular
      epithelial cells, high glucose (30 mM), but not equimolar mannitol, stimulated de
      novo protein synthesis and induced hypertrophy in association with increased
      phosphorylation of eukaryotic initiation factor 4E binding protein 1 and
      decreased phosphorylation of eukaryotic elongation factor 2, regulatory events in
      mRNA translation. These high-glucose-induced changes in protein synthesis were
      phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (mTOR)
      dependent and transforming growth factor-beta independent. High glucose reduced
      AMPK alpha-subunit theronine (Thr) 172 phosphorylation, which required Akt
      activation. Changes in AMP and ATP content could not fully account for high
      glucose-induced reductions in AMPK phosphorylation. Metformin and 5
      aminoimidazole-4-carboxamide-1beta-riboside (AICAR) increased AMPK
      phosphorylation, inhibited high-glucose stimulation of protein synthesis, and
      prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1
      and eukaryotic elongation factor 2. Expression of kinase-inactive AMPK further
      increased high-glucose-induced protein synthesis. Renal hypertrophy in rats with
      Type 1 diabetes was associated with reduction in AMPK phosphorylation and
      increased mTOR activity. In diabetic rats, metformin and AICAR increased renal
      AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy,
      without affecting hyperglycemia. AMPK is a newly identified regulator of renal
      hypertrophy in diabetes.

PMID- 17018842
TI  - Parameter estimation of feedback gain in a stochastic model of renal
      hemodynamics: differences between spontaneously hypertensive and Sprague-Dawley
      rats.
AB  - Proximal tubular pressure shows periodic self-sustained oscillations in
      normotensive rats but highly irregular fluctuations in spontaneously hypertensive
      rats (SHR). Although we have suggested that the irregular fluctuations in SHR
      represent low-dimensional deterministic chaos in tubuloglomerular feedback (TGF),
      they could also arise from other mechanisms, such as intrinsic instabilities in
      preglomerular vessels or inputs from neighboring, coupled nephrons. To test this
      possibility, we applied a parameter estimation procedure to a model of TGF, where
      a stochastic process was added to represent mechanisms not included explicitly in
      the model. In its deterministic version, the model can have chaotic dynamics
      arising from TGF. The model introduces random fluctuations into a parameter that
      determines the gain of TGF. The model shows a rich variety of dynamics ranging
      from low-dimensional deterministic oscillations and chaos to high-dimensional
      random fluctuations. To fit the data from normotensive rats, the model must
      introduce only a small variation in the feedback gain, and its estimates of that
      gain agree well with experimental values. These results support the use of the
      deterministic model of nephron dynamics in normotensive rats. In contrast, the
      irregular tubular pressure fluctuations in SHR were best described by a model
      dominated by random parameter fluctuations. The results point to the failure of
      simple mathematical models of nephron dynamics adequately to describe processes
      that are important for the irregular tubular pressure fluctuations and the need
      to consider other factors, such as differences in vascular function or nephron
      nephron interactions, in further work on this problem.

PMID- 17018844
TI  - The characterization of alpha5-integrin expression on tubular epithelium during
      renal injury.
AB  - The hallmark of progressive chronic kidney disease is the deposition of
      extracellular matrix proteins and tubulointerstitial fibrosis. Integrins mediate
      cell-extracellular matrix interaction and may play a role tubular epithelial
      injury. Murine primary tubular epithelial cells (TECs) express alpha(5)-integrin,
      a fibroblast marker and the natural receptor for fibronectin. Microscopy
      localized alpha(5)-integrin on E-cadherin-positive cells, confirming epithelial
      expression. The expression of alpha(5)-integrin increased in TECs grown on
      fibronectin and occurred in parallel with an upregulation of alpha-smooth muscle
      actin (alphaSMA), a marker of epithelial-mesenchymal transition (EMT). Exposure
      of TECs to transforming growth factor (TGF)-beta also increased TEC alpha(5)
      integrin expression in association with alphaSMA and EMT. Knock-down of alpha5
      integrin expression with short interfering RNA attenuated the TGF-beta induction
      of alphaSMA but did not alter morphologic EMT. Rather, alpha5-integrin was
      necessary for epithelial cell migration on fibronectin but not type IV collagen
      during cell spreading and epithelial wound healing in vitro. Immunohistochemistry
      revealed basolateral tubular epithelial alpha(5)-integrin expression in mouse
      kidneys after unilateral ureteric obstruction but not in contralateral control
      kidneys. In patient biopsies of nondiabetic kidney disease, alpha(5)-integrin
      expression was increased significantly in the renal interstitium. Focal
      basolateral staining was also detected in injured, but not in normal, tubular
      epithelium. In summary, these data show that TECs are induced to express alpha(5)
      integrin during EMT and tubular epithelial injury in vitro and in vivo. These
      results increase our understanding of the biology of integrins during EMT and
      tubular injury in chronic kidney disease.

PMID- 17018843
TI  - Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin.
AB  - Insulin receptors are widely distributed in the kidney and affect multiple
      aspects of renal function. In the proximal tubule, insulin regulates volume and
      acid-base regulation through stimulation of the Na(+)/H(+) exchanger NHE3. This
      paper characterizes the signaling pathway by which insulin stimulates NHE3 in a
      cell culture model [opossum kidney (OK) cell]. Insulin has two distinct phases of
      action on NHE3. Chronic insulin (24 h) activates NHE3 through the classic
      phosphatidylinositol 3-kinase-serum- and glucocorticoid-dependent kinase 1 (PI3K
      SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect
      can be blocked by the PI3K inhibitor wortmannin or a dominant-negative SGK1. We
      showed that SGK1 transcript and protein are expressed in rat proximal tubule and
      OK cells. We previously showed that glucocorticoids augment the effect of insulin
      on NHE3 (Klisic J, Hu MC, Nief V, Reyes L, Fuster D, Moe OW, Ambuhl PM. Am J
      Physiol Renal Physiol 283: F532-F539, 2002). Part of this can be mediated via
      induction of SGK1 by glucocorticoids, and indeed the insulin effect on NHE3 can
      also be amplified by overexpression of SGK1. We next addressed the acute effect
      of insulin (1-2 h) on NHE3 by systematically examining the candidate signaling
      cascades and activation mechanisms of NHE3. We ruled out the PI3K-SGK1-Akt and
      TC10 pathways, increased surface NHE3, NHE3 phosphorylation, NHE3 association
      with calcineurin homologous protein 1 or megalin as mechanisms of acute
      activation of NHE3 by insulin. In summary, insulin stimulates NHE3 acutely via
      yet undefined pathways and mechanisms. The chronic effect of insulin is mediated
      by the classic PI3K-SGK1 route.

PMID- 17018845
TI  - Inhibiting albumin glycation attenuates dysregulation of VEGFR-1 and collagen IV
      subchain production and the development of renal insufficiency.
AB  - Glomerular cells in culture respond to albumin containing Amadori glucose adducts
      (the principal serum glycated protein), with activation of protein kinase C
      beta(1), increased expression of transforming growth factor (TGF)-beta1, the TGF
      beta type II signaling receptor, and the extracellular matrix proteins
      alpha(1)(IV) collagen and fibronectin and with decreased production of the
      podocyte protein nephrin. Decreasing the burden of glycated albumin in diabetic
      db/db mice significantly reduces glomerular overexpression of TGF-beta1 mRNA,
      restores glomerular nephrin immunofluorescence, and lessens proteinuria,
      mesangial expansion, renal extracellular matrix protein production, and increased
      glomerular vascular endothelial growth factor (VEGF) immunostaining. In the
      present study, db/db mice were treated with a small molecule, designated 23CPPA,
      that inhibits the nonenzymatic condensation of glucose with the albumin protein
      to evaluate whether increased glycated albumin influences the production of VEGF
      receptors (VEGFRs) and type IV collagen subchains and ameliorates the development
      of renal insufficiency. Renal levels of VEGF and VEGFR-1 proteins and serum
      creatinine concentrations were significantly higher and renal levels of
      alpha(3)(IV) collagen and nephrin proteins and endogenous creatinine clearance
      values were significantly lower in control diabetic than in age-matched
      nondiabetic (db/m) mice. These changes were significantly attenuated in db/db
      littermate mice treated from 9 to 18 wk of age with 23CPPA. The findings indicate
      that inhibiting excess nonenzymatic glycation of serum albumin improves renal
      molecular biology abnormalities and protects against the development of renal
      insufficiency in the db/db mouse.

PMID- 17018846
TI  - WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria
      of familial hyperkalemic hypertension caused by gene mutation of WNK4.
AB  - The epithelial Ca(2+) channel TRPV5 serves as a gatekeeper for active Ca(2+)
      reabsorption in the distal convoluted tubule and connecting tubule of the kidney.
      WNK4, a protein serine/threonine kinase with gene mutations that cause familial
      hyperkalemic hypertension (FHH), including a subtype with hypercalciuria, is also
      localized in the distal tubule of the nephron. To understand the role of WNK4 in
      modulation of Ca(2+) reabsorption, we evaluated the effect of WNK4 on TRPV5
      mediated Ca(2+) transport in Xenopus laevis oocytes. Coexpression of TRPV5 with
      WNK4 resulted in a twofold increase in TRPV5-mediated Ca(2+) uptake. The increase
      in Ca(2+) uptake was due to the increase in surface expression of TRPV5. When the
      thiazide-sensitive Na(+)-Cl(-) cotransporter NCC was coexpressed, the effect of
      WNK4 on TRPV5 was weakened by NCC in a dose-dependent manner. Although the WNK4
      disease-causing mutants E562K, D564A, Q565E, and R1185C retained their ability to
      upregulate TRPV5, the blocking effect of NCC was further strengthened when wild
      type WNK4 was replaced by the Q565E mutant, which causes FHH with hypercalciuria.
      We conclude that WNK4 positively regulates TRPV5-mediated Ca(2+) transport and
      that the inhibitory effect of NCC on this process may be involved in the
      pathogenesis of hypercalciuria of FHH caused by gene mutation in WNK4.

PMID- 17018847
TI  - Renal injury in streptozotocin-diabetic Ren2-transgenic rats is mainly dependent
      on hypertension, not on diabetes.
AB  - Induction of streptozotocin (STZ) diabetes in hypertensive rats transgenic for
      the mouse ren-2 gene (TGR) has been described as a model of progressive diabetic
      nephropathy. We investigated the long-term course of STZ diabetes in TGR and
      appropriate Sprague-Dawley control rats (SD) and tested the role of angiotensin
      dependent hypertension by treating rats with the angiotensin II type 1 receptor
      blocker losartan (1 mg.kg(-1).day(-1)) via osmotic minipumps. Five weeks after
      STZ injection, diabetes developed in TGR and SD. Urinary albumin excretion was
      increased by diabetes and, to a much higher degree, by hypertension. The effects
      of hypertension and diabetes were not additive, and only the effects of
      hypertension were ameliorated by losartan. A similar pattern was observed for
      cell proliferation and macrophage infiltration in the kidney. In contrast, the
      effects of hypertension and diabetes on glomerular collagen IV accumulation were
      additive 5 wk after STZ injection. In a long-term study for 20 wk after STZ,
      survival was better in STZ-treated TGR than in normoglycemic TGR, whereas all SD
      survived. Impaired creatinine clearance and increased macrophage infiltration as
      well as glomerular and interstitial matrix deposition were prominent in TGR
      compared with SD, regardless of the presence or absence of diabetes. In
      conclusion, STZ diabetes in TGR may be useful to study glomerular and
      interstitial matrix deposition early in the course of diabetes. However, the long
      term course of this animal model resembles severe hypertensive nephrosclerosis,
      rather than progressive diabetic nephropathy.

PMID- 17018848
TI  - Administration of poly-D-glutamic acid induces proliferation of erythropoietin
      producing peritubular cells in rat kidney.
AB  - Erythropoietin (EPO), a 34-kDa glycoprotein, is produced predominantly by
      peritubular interstitial cells (PIC) in the renal cortex and is physiologically
      released when ambient oxygen pressure falls. However, the exact nature of EPO
      producing cells in the kidney is not well understood. We discovered that brief
      administration of a low-molecular-weight synthetic peptide, poly-D-glutamic acid
      (PDG), induced prompt and robust expansion of EPO-producing PIC in rat kidney,
      without evidence of tubular cell necrosis/apoptosis or fibrotic reaction.
      Proliferating PIC in PDG-treated rats were noninflammatory, alpha-smooth muscle
      actin negative, and specifically expressed CD73 (ecto-5'-nucleotidase), EPO mRNA,
      and protein. Increased numbers of EPO-positive PIC persisted even after the
      cessation of PDG treatment. No erythropoietic effects of EPO were detected,
      potentially suggesting maintained physiological control of EPO secretion in this
      normoxic model. We showed previously that PDG is readily filtered and is rapidly
      taken up and stored in lysosomes of proximal tubular cells (PTC), resulting in an
      apparently nonnoxious lysosomal storage condition by virtue of its
      nonhydrolyzable nature (Kishore BK, Maldague P, Tulkens PM, Courtoy PJ. Lab
      Invest 74: 1013-1023, 1996). Based on these findings, we suggest that unknown
      signaling molecules, produced by PTC in response to lysosomal PDG storage, appear
      to specifically stimulate the proliferation of EPO-producing PIC. We conclude
      that this model is uniquely suited to investigate the biology of EPO production
      by PIC and may thus facilitate the development of novel and more economical
      therapies of anemias and other EPO-responsive conditions.

PMID- 17018850
TI  - Variations on a theme: Hox and Wnt combinatorial regulation during animal
      development.
AB  - Shockingly few transcription factors and cell signaling pathways are utilized to
      pattern organs and to specify the fate of a seemingly endless variety of unique
      cell types during animal development. This dichotomy led to the hypothesis that
      each factor is used in multiple tissues and that a combinatorial code of factors
      determines cell fate or tissue identity in a unique fashion. Two recent papers
      describe temporal changes in the interplay between Hox transcription factors,
      which specify positional identity, and Wnt signaling, which provides spatial
      information and promotes asymmetric cell division. These changes guide cells
      through a series of discrete steps, leading to unique fates. Variations between
      these two studies highlight the diversifying potential of combinatorial
      regulation, in short, that the pathways through which these molecules interact
      can vary even between adjacent cells. Shared features include cross-regulatory
      interactions to redeploy patterning genes in a tissue-specific manner for
      organogenesis and coregulation of common downstream targets. Identification of
      additional combinatorial gene targets and elucidation of their underlying
      molecular mechanisms are important future tasks in developmental biology and the
      study of evolution.

PMID- 17018851
TI  - MAPping out arteries and veins.
AB  - Growing evidence suggests that a genetic program specifies the identity of
      arteries and veins before the onset of circulation. A signaling cascade involving
      sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), the VEGF
      receptor 2 (VEGFR2), homeobox proteins Foxc1 and Foxc2, the Notch receptor, and
      the downstream transcription factor gridlock is required for expression of
      arterial markers, whereas only a single transcription factor, COUP-TFII (chicken
      ovalbumin upstream promoter-transcription factor II), has previously been
      implicated in maintaining venous fate. Recent work has now implicated two
      competing pathways downstream of VEGFR2 in arterial versus venous specification:
      Activation of the phospholipase C-gamma (PLC-gamma)-mitogen-activated protein
      kinase (MAPK) pathway acts in arterial specification, whereas the
      phosphoinositide 3-kinase (PI3K)-Akt pathway acts to allow a venous fate by
      inhibition of the PLC-gamma-MAPK pathway. Here, we review this work and discuss
      how activation of the MAPK signaling cascade could stimulate an arterial fate.

PMID- 17018852
TI  - Gene control by large noncoding RNAs.
AB  - Large noncoding RNAs (lncRNAs) have emerged as key players in regulating various
      fundamental cellular processes. Recent reports identify a functional lncRNA, Evf
      2, that operates during development to control the expression of specific
      homeodomain proteins, and they provide important insights into the mechanism of
      cooperation between a newly discovered nuclear receptor co-repressor protein
      (SLIRP) and steroid receptor activator RNA. Evf-2 is the first example of lncRNA
      directly involved in organogenesis in vertebrates.

PMID- 17018853
TI  - Dendritic-cell maturation alters intracellular signaling networks, enabling
      differential effects of IFN-alpha/beta on antigen cross-presentation.
AB  - The broad and often contrasting effects of type I interferons (IFNs) in innate
      and adaptive immunity are belied by the signaling via a single receptor, IFN
      alpha receptor (IFNAR). Here, we show that IFN-alpha/beta induces opposing
      effects on the immunologic outcome of antigen cross-presentation depending on
      dendritic cell (DC) maturation status. Despite equivalent IFNAR expression,
      immature conventional DCs (cDCs) activate STAT1 in response to IFN-alpha/beta,
      whereas exposure of mature DCs to IFN-alpha/beta results in signaling via STAT4.
      Microarray analysis revealed numerous transcriptional changes resulting from the
      altered signaling. Importantly, STAT1 signaling resulted in significant
      inhibition of CD40L-induced IL-12 production, accounting for the inhibition of
      CD8+ T-cell activation. These data provide evidence for a molecular switch in
      signaling pathways concomitant with DC maturation that offers a novel mechanism
      by which DCs modulate the integration of signals from the surrounding
      environment.

PMID- 17018855
TI  - Down-regulation of RXRalpha expression is essential for neutrophil development
      from granulocyte/monocyte progenitors.
AB  - Neutrophil granulocytes (Gs) represent highly abundant and short-lived leukocytes
      that are constantly regenerated from a small pool of myeloid committed
      progenitors. Nuclear receptor (NR) family members are ligand-activated
      transcription factors that play key roles in cellular proliferation and
      differentiation processes including myelopoiesis. Retinoid X receptor alpha
      (RXRalpha) represents the predominant NR types I and II homo- and
      heterodimerization partner in myeloid cells. Here we show that human myeloid
      progenitors express RXRalpha protein at sustained high levels during macrophage
      colony-stimulating factor (M-CSF)-induced monopoiesis. In sharp contrast,
      RXRalpha is down-regulated during G-CSF-dependent late-stage neutrophil
      differentiation from myeloid progenitors. Down-regulation of RXRalpha is
      critically required for neutrophil development since ectopic RXRalpha inhibited
      granulopoiesis by impairing proliferation and differentiation. Moreover, ectopic
      RXRalpha was sufficient to redirect G-CSF-dependent granulocyte differentiation
      to the monocyte lineage and to promote M-CSF-induced monopoiesis. Functional
      genetic interference with RXRalpha signaling in hematopoietic progenitor/stem
      cells using a dominant-negative RXRalpha promoted the generation of late-stage
      granulocytes in human cultures in vitro and in reconstituted mice in vivo.
      Therefore, our data suggest that RXRalpha down-regulation is a critical
      requirement for the generation of neutrophil granulocytes.

PMID- 17018854
TI  - Preformed antibody, not primed T cells, is the initial and major barrier to bone
      marrow engraftment in allosensitized recipients.
AB  - Multiply-transfused individuals are at higher risk for BM rejection. We show that
      whereas allosensitization resulted in the priming of both cellular and humoral
      immunity, preformed antibody was the major barrier to engraftment. The generation
      of cross-reactive alloantibody led to rejection of BM of a different MHC
      disparate strain. Imaging studies indicated that antibody-mediated rejection was
      very rapid (<3 hours) in primed recipients, while T-cell-mediated rejection in
      nonprimed mice took more than 6 days. Antibody-mediated BM rejection was not due
      to a defect in BM homing as rejection occurred despite direct intra-BM infusion
      of donor BM. Rejection was dependent upon host FcR+ cells. BM cells incubated
      with serum from primed mice were eliminated in nonprimed recipients, indicating
      that persistent exposure to high-titer antibody was not essential for rejection.
      High donor engraftment was achieved in a proportion of primed mice by mega-BM
      cell dose, in vivo T-cell depletion, and high-dose immunoglobulin infusion. The
      addition of splenectomy to this protocol only modestly added to the efficacy of
      this combination strategy. These data demonstrate both rapid alloantibody
      mediated elimination of BM by host FcR+ cells and priming of host antidonor T
      cells and suggest a practical strategy to overcome engraftment barriers in primed
      individuals.

PMID- 17018856
TI  - Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for
      standard and high-risk Hodgkin lymphoma with no impairment of outcome.
AB  - Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival
      and minimize toxicity. The best regimen to achieve this has not yet been defined.
      A total of 108 patients with newly diagnosed HD and adverse prognostic factors
      were prospectively studied between 1999 and 2004. They were assigned to therapy
      according to defined risk stratification. Patients were defined depending on the
      International Prognostic Score (IPS). Those with IPS of 3 or higher received 2
      cycles of escalated therapy, including bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [EB]). All
      others received 2 cycles of standard BEACOPP (SB). Subsequent therapy was
      prospectively assigned following 2 cycles according to results of early interim
      67Ga or positron emission tomography/computed tomography (PET/CT). Following a
      positive interim scan, 4 cycles of EB were administered, whereas 4 cycles of SB
      were given to patients with a negative scan. The complete remission rate, the 5
      year event-free survival (EFS), and overall survival (OS) rates were 97%, 85% and
      90%, respectively. Relapse or progression occurred in 27% of patients with
      interim positive PET/CT versus 2.3% of negative scans (P<.02). Early interim
      fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT is a useful tool for
      adjustment of chemotherapy on an individual basis. Similar EFS and OS rates were
      observed for patients in both risk groups.

PMID- 17018857
TI  - Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time
      PCR after allogeneic stem cell transplantation in patients with myelofibrosis.
AB  - The JAK2-V617F mutation occurs in about 50% of patients with myelofibrosis and
      might be a reliable marker to monitor residual disease after allogeneic stem cell
      transplantation. We describe a new, highly sensitive (>or= 0.01%) real-time
      polymerase chain reaction (PCR) to monitor and quantify V617F-JAK2-positive cells
      after dose-reduced allogeneic stem cell transplantation. After 22 allogeneic stem
      cell transplantation procedures in 21 JAK2-positive patients with myelofibrosis,
      78% became PCR negative. In 15 of 17 patients (88%), JAK2 remained negative after
      a median follow-up of 20 months. JAK2 negativity was achieved after a median of
      89 days after allograft (range, 19-750 days). A significant inverse correlation
      was seen for JAK2 positivity and donor-cell chimerism (r:-0.91, P<.001). Four of
      5 patients who never achieved JAK2 negativity fulfilled during the entire follow
      up all criteria for complete remission recently proposed by the International
      Working Group, suggesting a major role for JAK2 measurement to determine depths
      of remission. In one case, residual JAK2-positive cells were successfully
      eliminated by donor lymphocyte infusion. In conclusion, allogeneic stem cell
      transplantation after dose-reduced conditioning induces high rates of molecular
      remission in JAK2-positive patients with myelofibrosis, and quantification of
      V617F-JAK2 mutation by real-time PCR allows the detection of minimal residual
      disease to guide adoptive immunotherapy.

PMID- 17018858
TI  - Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen.
AB  - Lymphocytes from lymphotoxin (LT) alpha-deficient mice, which lack segregation of
      their B- and T-cell areas, acquire normal organization following adoptive
      transfer into RAG-deficient recipients, identifying a non-B non-T cell in the
      segregation process. Here we show that a CD4+CD3- accessory cell is tightly
      associated with discrete VCAM-1-expressing stromal cells in B- and T-cell areas
      of the mouse spleen. CD4+CD3- cells express high levels of LTalpha, LTbeta, and
      tumor necrosis factor (TNF) alpha, which are the ligands for the LTbeta receptor
      and TNFR1 expressed by stromal cells. The expression of these ligands is
      functional, as transferring CD4+CD3- cells derived from either embryonic or adult
      tissues into LTalpha-deficient mice organizes B/T segregation and up-regulates
      CCL21 protein expression in areas where T cells are segregated from B cells. We
      propose that the function of CD4+CD3- cells is to form a link between primed CD4
      T cells and the underlying stromal elements, creating distinct microenvironments
      in which they enable effector responses.

PMID- 17018859
TI  - CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue
      integrity.
AB  - Homeostatic trafficking of lymphocytes through extralymphoid tissues has been
      recently observed, and a potential role in immune surveillance and the
      establishment of peripheral tolerance are considered. However, the mechanisms
      regulating lymphocyte recirculation through peripheral tissues under
      noninflammatory conditions are not well understood. Here, we demonstrate that the
      chemokine receptor CCR7 controls not only lymphocyte trafficking to and within
      secondary lymphoid organs but also homeostatic migration of T and B lymphocytes
      through nonlymphoid tissues. Lack of CCR7 results in a massive accumulation of
      lymphocytes in epithelial tissues. In particular, the gastrointestinal mucosal
      tissue of CCR7-/- mice is highly permissive for the formation of lymphoid
      aggregates, which develop into ectopic follicular structures with major topologic
      characteristics of lymph nodes. Flow cytometry analysis of CD4+ T cells derived
      from ectopic follicles revealed that CD44hiCD62Llo effector memory T cells
      predominate in the gastric lymphoid aggregates. In aged mice, lack of CCR7
      induced age-dependent histomorphologic changes in the stomach with profound
      cystic hyperplasia and an increased rate of mucosal proliferation resembling
      Menetrier disease. Thus, CCR7 regulates the cellular organization of visceral
      tissue by governing life-long recirculation of naive and memory lymphocytes under
      homeostatic conditions.

PMID- 17018860
TI  - Dual role for RhoA in suppression and induction of cytokines in the human
      neutrophil.
AB  - Production of tumor necrosis factor-alpha (TNFalpha) by the neutrophil (PMN) is a
      pivotal event in innate immunity, but the signals regulating TNFalpha induction
      in this primary cell are poorly understood. Herein, we use protein transduction
      to identify novel, opposing anti- and pro-cytokine-inducing roles for RhoA in the
      resting and lipopolysaccharide (LPS)-stimulated human PMN, respectively. In the
      resting cell, RhoA suppresses Cdc42 activation, IkappaBalpha degradation, nuclear
      factor-kappaB (NF-kappaB) activation, and induction of TNFalpha and NF-kappaB
      dependent chemokines. Suppression of TNFalpha induction by RhoA is Rho kinase
      alpha (ROCKalpha) independent, but Cdc42 dependent, because TNFalpha induction by
      C3 transferase is attenuated by inhibition of Cdc42, and constitutively active
      Cdc42 suffices to activate NF-kappaB and induce TNFalpha. By contrast, we also
      place RhoA downstream of p38 mitogen-activated protein kinase and Cdc42 in a
      novel LPS-activated pathway in which p38, Cdc42, and ROCKalpha all promote
      TNFalpha protein expression. The p65 subunit of NF-kappaB coprecipitates with
      RhoA in a manner sensitive to the RhoA activation state. Our findings suggest a
      new, 2-faced role for RhoA as a checkpoint in innate immunity.

PMID- 17018861
TI  - Glucocorticoids induce differentiation of a specifically activated, anti
      inflammatory subtype of human monocytes.
AB  - Monocytes and macrophages may either promote or down-regulate inflammatory
      reactions depending on their state of activation. The effects of glucocorticoids
      (GCs), the most widely used immunosuppressive drugs, on monocytes are currently
      not well defined. By analyzing the GC-induced expression pattern in human
      monocytes by microarray technology, we identified for the first time GC-dependent
      regulation of 133 genes, including anti-inflammatory molecules such as adenosine
      A3 receptor, CD1d, and IL-1 receptor II. The results were independently confirmed
      by real-time polymerase chain reaction (PCR) and flow cytometry. Functional
      clustering of GC-regulated genes indicated induction of monocytic properties such
      as phagocytosis and motility as well as repression of adhesion, apoptosis, and
      oxidative burst. These predictions were confirmed by independent functional
      assays. GCs up-regulate fMLP receptors and specifically promote chemotaxis to
      this chemoattractant. Furthermore, GCs promote survival of an anti-inflammatory
      monocytic phenotype in inflammatory reactions, probably by inhibition of
      apoptosis because of oxidative stress. GCs limit tissue damage because of
      induction of antioxidative properties and high capacity for phagocytosis of
      proinflammatory agents. Thus, GC treatment did not cause a global suppression of
      monocytic effector functions but results in differentiation of a specific anti
      inflammatory phenotype which seems to be actively involved in resolution of
      inflammatory reactions.

PMID- 17018862
TI  - Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear
      translocation of the transcription factor Bach2, which represses the
      antiapoptotic factor heme oxygenase-1.
AB  - The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal
      tyrosine kinase activity of the Bcr-Abl oncoprotein. We have previously reported
      that expression of the Bach2 transcription factor, which induces apoptosis in
      response to oxidative stress, is greatly reduced in CML cells. Because these
      cells are resistant to apoptosis, we tested whether Bach2 could also be regulated
      through posttranslational mechanisms that promote inhibition of the apoptotic
      response to mutagenic stimuli in CML. We found that Bach2 is phosphorylated on
      S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this
      site to alanine leads to nuclear accumulation of the protein, indicating that
      this phosphorylation is important for its subcellular localization. Ectopic
      expression of the S521 mutant imparts greater impairment to CML cell growth than
      the wild-type factor. Furthermore, we showed that Bach2 transcriptionally
      represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML. Because
      CML cells are known to produce high levels of intracellular reactive oxygen
      species, overexpression of heme oxygenase-1 resulting from inhibition of Bach2
      activity may contribute to their genomic instability and leukemic phenotype.

PMID- 17018863
TI  - Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr
      virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice.
AB  - Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative
      disease (PTLD), which is a leading cause of cancer death in recipients of
      transplants. We investigated the role of plasmacytoid dendritic cells (PDCs) in
      the development of EBV infection and the onset of lymphoproliferative disease
      (LPD) in humanized NOD-SCID mice and studied the effect of EBV on PDC function.
      NOD-SCID mice reconstituted with PDC-depleted peripheral blood mononuclear cells
      (PBMCs) from EBV IgG+ human donors had significantly enhanced mortality from
      disseminated EBV infection (median survival, 43 days) compared to PBMC-only mice
      (median survival, 72 days; log-rank P<.05). Mice reconstituted with PDC-enriched
      PBMCs challenged with EBV exhibited delayed mortality from EBV-LPD (median
      survival, 80 days) compared to PBMC-only mice challenged with EBV (median
      survival, 50 days; log-rank P<.05). EBV-stimulated pDCs produced interferon alpha
      (IFN-alpha) and promoted the activation of natural killer cells and IFN-gamma
      producing CD3+T cells. PDC activation of CD3+T cells in response to EBV
      stimulation was dependent on cell-to-cell contact, in part mediated by toll-like
      receptor 9 (TLR-9) signaling that was inhibited by chloroquine and TLR-9
      inhibitory CpG. Thus, PDCs play an important role in anti-EBV cellular immune
      responses that may be targets for manipulation in novel strategies for the
      treatment of PTLD.

PMID- 17018864
TI  - Visceral pain perception is determined by the duration of colitis and associated
      neuropeptide expression in the mouse.
AB  - BACKGROUND: Even though inflammation is a traditional tool for the induction of
      hyperalgesia in many tissues, recent observations suggest that not all
      inflammatory processes produce this change. Tolerance to colorectal distension
      (CRD) is reduced in patients with acute ulcerative colitis but is increased in
      patients with chronic inflammatory bowel disease. This suggests that the nature
      of the inflammatory infiltrate influences visceral perception. AIM: To test this
      hypothesis by assessing responses to CRD in mice with mild, acute or chronic
      colitis. METHODS: CRD responses were measured in mice with mild non-specific
      colitis, and dextran sodium sulphate (DSS)-induced acute and chronic colitis.
      Responses were compared with tissue infiltrate and damage, interleukin (IL)1beta
      and myeloperoxidase (MPO) activity and substance P, beta-endorphin and micro
      opioid receptor (MOR) expression. RESULTS: Mild and acute colitis were associated
      with increased responsiveness to CRD. In contrast, CRD responses were not
      increased in mice with chronic colitis and this difference was not due to altered
      colonic wall compliance. MPO and IL1beta levels were greater in acute than in
      chronic colitis. Larger increases in tissue substance P were seen in acute than
      in chronic DSS, whereas CD4 T cells, beta-endorphin and MOR expression were
      evident only in chronic colitis. An inverse correlation was seen between
      substance P and MOR in these tissues. CONCLUSIONS: Acute colitis increased
      responsiveness to CRD and is accompanied by an acute inflammatory infiltrate and
      increased tissue substance P. Chronic DSS is accompanied by an increase in beta
      endorphin and MOR expression, and CD4 T cells, but no change in compliance or CRD
      responses. We conclude that acute inflammation generates hyperalgesia, whereas
      chronic inflammation involves infiltration by lymphocytes accompanied by MOR and
      beta-endorphin up regulation, and this provides an antinociceptive input that
      restores normal visceral perception.

PMID- 17018866
TI  - Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal
      models of neuroinflammation.
AB  - In recent years it has become increasingly clear that the metallothionein (MT)
      family of proteins is important in neurobiology. MT-I and MT-II are normally
      dramatically up-regulated by neuroinflammation. Results for MT-III are less
      clear. MTs could also be relevant in human neuropathology. In Alzheimer disease
      (AD), a major neurodegenerative disease, clear signs of inflammation and
      oxidative stress were detected associated with amyloid plaques. Furthermore, the
      number of cells expressing apoptotic markers was also significantly increased in
      these plaques. As expected, MT-I and MT-II immunostaining was dramatically
      increased in cells surrounding the plaques, consistent with astrocytosis and
      microgliosis, as well as the increased oxidative stress elicited by the amyloid
      deposits. MT-III, in contrast, remained essentially unaltered, which agrees with
      some but not all studies, of AD. In situ hybridization results in a transgenic
      mouse model of AD amyloid deposits, the Tg2576 mouse, which expresses human Abeta
      precursor protein harboring the Swedish K670N/M671L mutations, are in accordance
      with results in human brains. Overall, these and other studies strongly suggest
      specific roles for MT-I, MT-II, and MT-III in brain physiology.

PMID- 17018867
TI  - Metallothionein redox cycle and function.
AB  - The biologic function of metallothionein (MT) has been a perplexing topic ever
      since the discovery of this protein. Many studies have suggested that MT plays a
      role in the homeostasis of essential metals such as zinc and copper,
      detoxification of toxic metals such as cadmium, and protection against oxidative
      stress. However, mechanistic insights into the actions of MT have not been
      adequately achieved. MT contains high levels of sulfur. The mutual affinity of
      sulfur and transition metals makes the binding of these metals to MT
      thermodynamically stable. Under physiologic conditions, zinc-MT is the
      predominant form of the metal-binding protein. The recognition of the redox
      regulation of zinc release from or binding to MT provides an alternate
      perspective on biologic function of MT. Oxidation of the thiolate cluster by a
      number of mild cellular oxidants causes zinc release and formation of MT
      disulfide (or thionin if all metals are released from MT, but this is unlikely to
      occur in vivo), which have been demonstrated in vivo. Therefore, the
      thermodynamic stability of zinc binding makes MT an ideal zinc reservoir in vivo,
      and the redox regulation of zinc mobilization enables MT function in zinc
      homeostasis. MT-disulfide can be reduced by glutathione in the presence of
      selenium catalyst, restoring the capacity of the protein to bind zinc. This MT
      redox cycle may play a crucial role in MT biologic function. It may link to the
      homeostasis of essential metals, detoxification of toxic metals and protection
      against oxidative stress.

PMID- 17018868
TI  - Metallothioneins: mercury species-specific induction and their potential role in
      attenuating neurotoxicity.
AB  - Metallothionein (MT) proteins are widespread in bacteria, fungi, plants, and
      eukaryotic species. They are of low molecular weight (6-7 kDa) and of the 60+
      amino acid residues, 20 are cysteines. Functions attributed to MTs include the
      sequestration and dispersal of metal ions, primarily in zinc and copper
      homeostasis; regulation of the biosynthesis and activity of zinc metalloproteins,
      most notably zinc-dependent transcription factors; and cellular cytoprotection
      from reactive oxygen species, ionizing radiation, electrophilic anticancer drugs
      and mutagens, and metals. Observations on the abundance of MTs within the central
      nervous system (CNS) and the identification of a brain-specific isoform, MT-III,
      suggest that it might have important neurophysiological and neuromodulatory
      functions. Reinforced by the potential involvement of MT-III in a number of
      neurodegenerative disorders, the role of MTs in the CNS has become an intense
      focus of scientific pursuit. This manuscript represents a survey on the ability
      of MTs to modulate mercury neurotoxicity, a neurotoxin that has been implied to
      play an etiologic role in Minamata disease, erethism, and autism, just to name a
      few.

PMID- 17018869
TI  - Effect of soluble nickel on cellular energy metabolism in A549 cells.
AB  - Iron is an essential nutrient to most organisms, and is actively involved in
      oxygen delivery, electron transport, DNA synthesis, and many other biochemical
      reactions important for cell survival. We previously reported that nickel (Ni)
      ion exposure decreases cellular iron level and converts cytosolic aconitase (c
      aconitase) to iron-regulatory protein-1 in A549 cells (Chen H, Davidson T,
      Singleton S, Garrick MD, Costa M. Toxicol Appl Pharmacol 206:275-287, 2005).
      Here, we further investigated the effect of Ni ion exposure on the activity of
      mitochondrial iron-sulfur (Fe-S) enzymes and cellular energy metabolism. We found
      that acute Ni ion treatment up to 1 mM exhibits minimal toxicity in A549 cells.
      Ni ion treatment decreases the activity of several Fe-S enzymes related to
      cellular energy metabolism, including mitochondrial aconitase (m-aconitase),
      succinate dehydrogenase (SDH), and NADH:ubiquinone oxidoreductase (complex I).
      Low doses of Ni ion for 4 weeks resulted in an increased cellular glycolysis and
      NADH to NAD+ (NADH/NAD+) ratio, although glycolysis was inhibited at higher
      levels. Collectively, our results show that Ni ions decrease the activity of
      cellular iron (Fe)-containing enzymes, inhibit oxidative phosphorylation
      (OxPhos), and increase cellular glycolytic activity. Since increased glycolysis
      is one of the fundamental alterations of energy metabolism in cancer cells (the
      Warburg effect), the inhibition of Fe-S enzymes and subsequent changes in
      cellular energy metabolism caused by Ni ions may play an important role in Ni
      carcinogenesis.

PMID- 17018870
TI  - Metals in motor neuron diseases.
AB  - Degenerative processes within the nervous system are common features in disease
      entities such as dementia of Alzheimer type (DAT), Parkinson disease (PD), and
      amyotrophic lateral sclerosis (ALS). ALS is a neurodegenerative disease with
      unknown etiology; widespread muscle wasting and respiratory failure lead to death
      within a few years. Denervation can be detected with electromyography and axonal
      deterioration monitored by motor unit number estimates. Several suggestions about
      the cause of ALS have emerged but no solid theory has yet precipitated. Lead or
      mercury exposure has been suggested. Exposure data alone cannot support this
      connection. Alterations in metal kinetics may underlie the deterioration of motor
      function observed in patients with ALS. In this review the role of metals in
      motor neuron disease is discussed. Both classic studies on exposure and recent
      understanding of metal binding proteins are considered. Aspects of peak exposure
      and excretion are merged toward an understanding of metal dynamics in ALS. An
      overview of chemical and electrophysiological investigations is given in the
      context of neurodegeneration.

PMID- 17018871
TI  - Peptide folding, metal-binding mechanisms, and binding site structures in
      metallothioneins.
AB  - This minireview specifically focuses on recent studies carried out on structural
      aspects of metal-free metallothionein (MT), the mechanism of metal binding for
      copper and arsenic, structural studies using x-ray absorption spectroscopy and
      molecular mechanics modeling, and speciation studies of a novel cadmium and
      arsenic binding algal MT. Molecular mechanics-molecular dynamics calculations of
      apo-MT show that significant secondary structural features are retained by the
      polypeptide backbone upon sequential removal of the metal ions, which is
      stabilized by a possible H-bonding network. In addition, the cysteinyl sulfurs
      were shown to rotate from within the domain core, where they are found in the
      metallated state, to the exterior surface of the domain, suggesting an
      explanation for the rapid metallation reactions that were measured. Mixing
      Cu6beta-MT with Cd4alpha-MT and Cu6alpha-MT with Cd3beta-MT resulted in
      redistribution of the metal ions to mixed metal species in each domain; however,
      the Cu+ ions preferentially coordinated to the beta domain in each case. Reaction
      of As3+ with the individual metal-free beta and alpha domains of MT resulted in
      three As3+ ions coordinating to each of the domains, respectively, in a proposed
      distorted trigonal pyramid structure. Kinetic analysis provides parameters that
      allow simulation of the binding of each of the As3+ ions. X-ray absorption
      spectroscopy provides detailed information about the coordination environment of
      the absorbing element. We have combined measurement of x-ray absorption near edge
      structure (XANES) and extended x-ray absorption fine structure (EXAFS) data with
      extensive molecular dynamics calculations to determine accurate metal-thiolate
      structures. Simulation of the XANES data provides a powerful technique for
      probing the coordination structures of metals in metalloproteins. The metal
      binding properties of an algal MT, Fucus vesiculosus, has been investigated by UV
      absorption and circular dichroism spectroscopy and electrospray ionization-mass
      spectrometry. The 16 cysteine residues of this algal MT were found to coordinate
      six Cd2+ ions in two domains with stoichiometries of a novel Cd3S7 cluster and a
      beta-like Cd3S9 cluster.

PMID- 17018872
TI  - Metallothionein-3 is a component of a multiprotein complex in the mouse brain.
AB  - Metallothionein (MT)-3, originally called growth inhibitory factor (GIF), was
      initially identified through its ability to inhibit the growth of neuronal cells
      in the presence of brain extract. MT-3 is the brain specific isoform of the MT
      family whose specific biological activity associates it with neurological
      disorders. Indeed, studies report that MT-3 is decreased by ~30% in brains of
      patients with Alzheimer disease (AD). Furthermore, many lines of evidence suggest
      that MT-3 engages in specific protein interactions. To address this, we conducted
      immunoaffinity chromatography experiments using an immobilized anti-mouse MT-3
      antibody. We identified five associated proteins from the pool of sixteen
      recovered using mass spectrometry and tandem mass spectrometry after in-gel
      trypsin digestion of bands from the affinity chromatography. The proteins
      identified were: heat shock protein 84 (HSP84), heat shock protein 70 (HSP70),
      dihydropyrimidinase-like protein-2 (DRP-2), creatine kinase (CK) and beta-actin.
      Coimmunoprecipitation experiments, also conducted on whole mouse brain extract
      using the anti-mouse MT-3 antibody along with commercially available antibodies
      against HSP84 and CK, confirmed that these three proteins were in a single
      protein complex. Immunohistochemical experiments were then conducted on the
      perfused mouse brain that confirmed the in situ colocalization of CK and MT-3 in
      the hippocampus region. These data provide new insights into the involvement of
      MT-3 in a multiprotein complex, which will be used to understand the biological
      activity of MT-3 and its role in neurological disease.

PMID- 17018873
TI  - Cell-surface protein disulfide isomerase is required for transnitrosation of
      metallothionein by S-nitroso-albumin in intact rat pulmonary vascular endothelial
      cells.
AB  - S-nitrosation of the metal binding protein, metallothionein (MT) appears to be a
      critical link in affecting endothelial nitric oxide synthase (eNOS) and inducible
      nitric oxide synthase (iNOS)-derived nitric oxide (NO)-induced changes in
      cytoplasmic and nuclear labile zinc, respectively. Although low molecular weight
      S-nitrosothiols also appear to affect this signaling system, less is known about
      the ability of extracellular protein nitrosothiols to transnitrosate MT.
      Accordingly, we synthesized fluorescently labeled S-nitroso-albumin (SNO-albumin,
      a major protein S-nitrosothiol in plasma) and determined, via confocal microscopy
      in fixed tissue, that it is transported into cultured rat pulmonary vascular
      endothelial cells in a temperature sensitive fashion. The cells were transfected
      with an expression vector that encodes human MT-IIa cDNA sandwiched between
      enhanced cyan (donor) and yellow (acceptor) fluorescent proteins (FRET-MT) that
      can detect conformational changes in MT through fluorescence resonance energy
      transfer (FRET). SNO-albumin and the membrane-permeant low molecular weight S
      nitroso-l-cysteine ethyl ester (l-SNCEE) caused a conformational change in FRET
      MT as ascertained by full spectral laser scanning confocal microscopy in live rat
      pulmonary vascular endothelial cells, a result which is consistent with
      transnitrosation of the reporter molecule. Transnitrosation of FRET-MT by SNO
      albumin, but not l-SNCEE, was sensitive to antisense oligonucleotide-mediated
      inhibition of the expression of cell surface protein disulfide isomerase (csPDI).
      These results extend the original observations of Ramachandran et al.
      (Ramachandran N, Root P, Jiang XM, Hogg PJ, Mutus B. Proc Natl Acad Sci U S A 98:
      9539-9544, 2001) and suggest that csPDI-mediated denitrosation helps to regulate
      the ability of the major plasma NO carrier (SNO-albumin) to transnitrosate
      endothelial cell molecular targets (e.g. MT).

PMID- 17018874
TI  - Metallothionein as a prognostic biomarker in breast cancer.
AB  - Breast cancer is the most common cancer in women, with a general upward trend in
      incidence. Basic and clinical breast cancer research has continued at a rapid
      pace, in the endeavor to understand the biology of the disease so as to improve
      management of patients. Besides traditional pathological indicators, expression
      of molecular markers in breast cancer has also been comprehensively investigated.
      This paper will focus on the prognostic utility of metallothioneins (MTs), a
      family of low molecular weight metal binding proteins encoded by at least 10
      functional MT genes that are associated with cell proliferation in breast cancer.
      Evidence that MT is a potential prognostic biomarker for breast cancer is
      supported by many reports in the literature. Expression of the MT protein has
      been detected by immunohistochemistry in a significant portion of invasive ductal
      breast cancers. MT expression has also been well studied in association with
      traditional clinico-pathological parameters of breast cancers. Generally, higher
      MT expression in breast cancers is predictive of worse patient outcomes. The
      relationship of MT isoforms to histological grade, estrogen receptor (ER) status,
      and prognosis will also be discussed.

PMID- 17018875
TI  - The Zn- and Cd-clusters of recombinant mammalian MT1 and MT4 metallothionein
      domains include sulfide ligands.
AB  - Recombinant (E. coli ) synthesis of mammalian MT1 and MT4 domains as separate
      peptides in Zn(II) and Cd(II) enriched growth media has rendered metal complexes
      containing sulfide anions as additional ligands. The Cd preparations show higher
      sulfide content than the Zn preparations. Also, the betaMT1 and betaMT4 fragments
      exhibit higher sulfide/peptide ratios than the respective alpha fragments.
      Titration of Zn3-betaMT1 with Cd(II) followed by addition of several sodium
      sulfide equivalents shows that the Cd(II)-betaMT1 species can incorporate sulfide
      ligands in vitro, with a concomitant evolution of their UV-vis and CD
      fingerprints to those characteristic of the Cd-S2- chromophores. Current results
      have also provided full understanding of previous data collected by this group in
      the characterization of the Cd-betaMT1 preparations obtained from large-scale
      fermentor synthesis by allowing identification of at least 2S2- ligands per Cd
      betaMT1 species. Furthermore, the results here presented have revealed that
      synthesis of betaMT4 in Cd-supplemented cultures yielded Cd,S(2-)-containing
      clusters instead of the proposed heterometallic Zn,Cd-betaMT4 complexes. Finally,
      a global evaluation of our results suggests that the higher the Cu-thionein
      character of a MT peptide, the higher is its tendency to harbor nonproteic
      ligands (i.e., sulfide anions) when building divalent metal clusters, especially
      Cd-MT complexes.

PMID- 17018876
TI  - Apo-metallothionein emerging as a major player in the cellular activities of
      metallothionein.
AB  - Observations of apo-metallothionein (apo-MT) have been made under a variety of
      physiologic circumstances, including zinc deficiency in cell culture and in
      rodents, cellular induction of MT by dexamethasone with concurrent Zn deficiency,
      a variety of tumors under normal Zn conditions, MT induction by Zn and Bi
      citrate, induction of hepatic MT after tumor cell injection into nude mice, and
      overexpression of cardiac MT in MT transgenic mice. Experiments demonstrating
      both the lability of Zn and Cu bound to MT and the cellular stability of apo-MT
      are described to help rationalize the widespread presence of this metal-depleted
      species. Finally, comparative in vitro and cellular experiments examined the
      relative reactivity of Zn- and apo-MT with nitric oxide species, showing that apo
      MT is much more reactive chemically and that in cells it may be a principal
      reactive species within the MT pool.

PMID- 17018877
TI  - Differential effects between maotai and ethanol on hepatic gene expression in
      mice: Possible role of metallothionein and heme oxygenase-1 induction by maotai.
AB  - Alcohol is a risk factor for liver fibrosis and hepatocellular carcinoma. On the
      other hand, light alcoholic beverage consumption is believed to be beneficial
      because of the effects of both alcohol and nonalcoholic components of the
      beverage. Maotai is a commonly consumed beverage in China containing 53% alcohol.
      Epidemiological and experimental studies show that Maotai is less toxic to the
      liver than ethanol alone. To examine the differential effects of Maotai and
      ethanol, a low dose of Maotai or an equal amount of ethanol (53%, v/v in water, 5
      ml/kg) were given to male mice daily for 1 week, and hepatic RNA was extracted
      for microarray analysis. Approximately 10% of genes on the liver-selective custom
      array (588 genes) were altered following Maotai or ethanol administration, but
      Maotai treated livers had fewer alterations compared with ethanol alone. Real
      time reverse transcription-polymerase chain reaction confirmed and extended
      microarray results on selected genes. An induction of metallothionein and heme
      oxygenase-1 occurred with Maotai, which could not be explained by alcohol
      consumption alone, whereas the attenuation of ethanol responsive genes such as
      quinone dehydrogenase, DNA-ligase 1, IGFBP1, and IL-1beta suggests less liver
      injury occurred with Maotai. The expression of genes related to liver fibrosis,
      such as cytokeratin-18, was slightly increased by the high dose of ethanol, but
      was unchanged in the Maotai group. In summary, gene expression analysis indicates
      that Maotai induces a different response than ethanol alone. The dramatic
      induction of metallothionein and heme oxygenase-1 with Maotai could be important
      adaptive responses to reduce alcoholic liver injury.

PMID- 17018878
TI  - Hepatic responses to dietary stress in zinc- and metallothionein-deficient mice.
AB  - Metallothionein (MT) and zinc are both reported to be protective against
      oxidative and inflammatory stress and may also influence energy metabolism. The
      role of MT in regulating intracellular labile zinc, thus influencing zinc (Zn)
      modulated protein activity, may be a key factor in the response to stress and
      other metabolic challenges. The objective of this study was to investigate the
      influence of dietary zinc intake and MT on hepatic responses to a pro-oxidant
      stress and energy challenge in the form of a high dietary intake of linoleic
      acid, an omega-6 polyunsaturated fatty acid. Male MT-null (KO) and wild-type (WT)
      mice, aged 16 weeks, were given semisynthetic diets containing 16% fat and either
      5 (marginally zinc-deficient [ZD]) or 35 (zinc-adequate [ZA]) mg Zn/kg. For
      comparison, separate groups of KO and WT mice were given a rodent chow diet
      containing 3.36% fat and 86.6 mg Zn/kg. After 4 months on these diets, the body
      weights of all mice were equal, but liver size, weight, and lipid content were
      much greater in the animals that consumed semisynthetic diets compared to the
      chow diet. The increase in liver size was significantly lower in ZA but not ZD KO
      mice, compared with WT mice. Principally, MT appears to affect the diet-induced
      increase in liver tissue but it also influences the concentration of hepatic
      lipid. Plasma levels of C-reactive protein (CRP), a marker of inflammation, were
      increased by zinc deficiency in WT mice, suggesting that marginal zinc deficiency
      is proinflammatory. CRP was unaffected by zinc deficiency in KO mice, indicating
      a role for MT in modulating the influence of zinc. Neither zinc nor MT deficiency
      affects the level of soluble liver proteins, as determined using two-dimensional
      (2D) gel proteomics. This study highlights the close association between zinc and
      MT in the manifestation of stress responses.

PMID- 17018879
TI  - The physiological roles of extracellular metallothionein.
AB  - Metallothionein (MT) is a low-molecular-weight protein with a number of roles to
      play in cellular homeostasis. MT is synthesized as a consequence of a variety of
      cellular stressors, and has been found in both intracellular compartments and in
      extracellular spaces. The intracellular pool of this cysteine-rich protein can
      act as a reservoir of essential heavy metals, as a scavenger of reactive oxygen
      and nitrogen species, as an antagonist of toxic metals and organic molecules, and
      as a regulator of transcription factor activity. The presence of MT outside of
      cells due to the influence of stressors suggests that this protein may make
      important contributions as a "danger signal" that influences the management of
      responses to cellular damage. While conventional wisdom has held that
      extracellular MT is the result of cell death or leakage from stressed cells,
      there are numerous examples of selective release of proteins by nontraditional
      mechanisms, including stress response proteins. This suggests that MT may
      similarly be selectively released, and that the pool of extracellular MT
      represents an important regulator of various cellular functions. For example,
      extracellular MT has effects both on the severity of autoimmune disease, and on
      the development of adaptive immune functions. Extracellular MT may operate as a
      chemotactic factor that governs the trafficking of inflammatory cells that move
      to resolve damaged tissues, as a counter to extracellular oxidant-mediated
      damage, and as a signal that influences the functional behavior of wounded cells.
      A thorough understanding of the mechanisms of MT release from cells, the
      conditions under which MT is released to the extracellular environment, and the
      ways in which MT interacts with sensitive cells may both illuminate our
      understanding of an important control mechanism that operates in stressful
      conditions, and should indicate new opportunities for therapeutic management via
      the manipulation of this pool of extracellular MT.

PMID- 17018880
TI  - Cytotoxicity of nitric oxide is alleviated by zinc-mediated expression of
      antioxidant genes.
AB  - Metallothioneins (MTs) are small, cysteine-rich zinc binding proteins that are
      powerful antioxidants. In this study, we investigated the interaction between
      zinc, MTs, and other components of the antioxidant defense system in HepG2 cells.
      Cells were preincubated with zinc and then exposed to sodium nitroprusside (SNP),
      a nitric oxide (NO) donor. Both zinc pretreatment and SNP exposure separately
      induced transcription of MT genes (MT1A, MT2A, MT1E, MT1X), as measured using
      real time-polymerase chain reaction (PCR) after reverse transcription (RT).
      Pretreatment of HepG2 cells with zinc sulfate (ZnSO4) followed by SNP exposure
      caused MT and glucose-6-phosphate dehydrogenase (G6PD) mRNA levels to increase
      more than in cells only exposed to SNP. However, when cells were incubated with
      N,N,N',N'-tetrakis(2-pyridylmethyl)ethyl-enediamine (TPEN), a membrane-permeant
      Zn2+ chelator, the stimulation of MT transcription by SNP was blocked, suggesting
      that SNP-induced upregulation of these genes is zinc-dependent. Human glutathione
      S-transferase (hGSTA1) and G6PD mRNA levels in the cells treated with 5 microM
      TPEN decreased. Additionally, the induction of MT by SNP after zinc pretreatment
      appears to be mediated by metal-activated transcription factor-1 (MTF-1), which
      is induced by labile zinc in the cytosol. SNP cytotoxicity was inhibited by
      preincubation with zinc. Taken together, these results suggest that NO plays an
      important role in regulation of cellular zinc homeostasis and that NO-mediated
      release of protein-bound Zn2+ may be an important signal in antioxidant defense.

PMID- 17018881
TI  - Effects of zinc on the induction of metallothionein isoforms in hippocampus in
      stress rats.
AB  - Metallothioneins (MTs) are involved in the cellular metabolism of zinc and in
      cytoprotection against stress factors. Hippocampus plays a specific role in the
      body's response to stressors. The present study was conducted to evaluate the
      effects of zinc on the expression of metallothionein isoforms in the hippocampus
      of stress rats. The animal model of psychologic stress was developed by restraint
      for 4 weeks. Wistar rats were randomly assigned to 6 groups: control group, zinc
      deficient group, zinc-supplemented group, and the corresponding 3 stress groups.
      Three separate diets of different zinc contents (1.73 ppm, 17.7 ppm, and 41.4
      ppm, respectively) were used in this study. Compared with the control group, the
      stress groups had higher inductions of MTs and MT-1 and MT-3 mRNA in hippocampus.
      On the one hand, the expressions of MTs and their mRNAs in hippocampus were
      downregulated in the zinc-deficient group; however, their expressions were
      evidently enhanced in the stress zinc-deficient group. MT induction in the zinc
      supplemented group was increased. Furthermore, the stress zinc-supplemented group
      had a more significant yield of MTs and their mRNAs. In addition, the levels of
      plasma cortisol, interleukin-6 (IL-6), IL-1, and nitric oxide (NO) were increased
      clearly in the zinc-deficient group and the stress groups. The results suggest
      that zinc deficiency may decrease and zinc supplementation may increase the
      expressions of MTs and their mRNAs in hippocampus; moreover, stress can increase
      their expressions dramatically. The impairment of stress on the body may be
      involved with the nutrition status of zinc, and zinc deficiency can lower the
      body's adaptability to stress.

PMID- 17018882
TI  - In vitro interaction between homocysteine and copper ions: Potential redox
      implications.
AB  - Homocysteine (Hcys) has been implicated in various oxidative stress-related
      disorders. The presence of a thiol on its structure allows Hcys to exert a double
      edge redox action. Depending on whether Cu2+ ions occur concomitantly, Hcys can
      either promote or prevent free radical generation and its consequences. We have
      addressed in vitro the interaction between Hcys and Cu2+ ions, in terms of the
      consequences that such interaction may have on the free radical scavenging
      properties of Hcys and on the redox state and redox activity of the metal. To
      this end, we investigated the free radical-scavenging, O2(*-)-generating, and
      ascorbate-oxidizing properties of the interacting species by assessing the
      bleaching of ABTS*+ radicals, the reduction of O2(*-)-dependent cytochrome c, and
      the copper-dependent oxidation of ascorbate, respectively. In addition, electron
      paramagnetic resonance and Cu(I)-bathocuproine formation were applied to assess
      the formation of paramagnetic complexes and the metal redox state. Upon a brief
      incubation, the Hcys/Cu2+ interaction led to a decrease in the free radical
      scavenging properties of Hcys, and to a comparable loss of the thiol density.
      Both effects were partial and were not modified by increasing the incubation
      time, despite the presence of Cu2+ excess. Depending on the molar Hcys:Cu2+
      ratio, the interaction resulted in the formation of mixtures that appear to
      contain time-stable and ascorbate-reducible Cu(II) complexes (for ratios up to
      2:1), and ascorbate- and oxygen-redox-inactive Cu(I) complexes (for ratios up to
      4:1). Increasing the interaction ratio beyond 4:1 was associated with the sudden
      appearance of an O2(*-)-generating activity. The data indicate that depending on
      the molar ratio of interaction, Hcys and Cu2+ react to form copper complexes that
      can promote either antioxidant or pro-oxidant actions. We speculate that the
      redox activity arising from a large molar Hcys excess may partially underlie the
      association between hyper-homocysteinemia and a greater risk of developing
      oxidative-related cardiovascular diseases.

PMID- 17018883
TI  - Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in
      Parkinson disease.
AB  - We have examined potent peroxynitrite ion (ONOO-) generator 3
      morpholinosydnonimine (SIN-1)-induced neurotoxicity in control wild-type
      (control(wt)) mice, metallothionein double knockout (MT(dko)) mice,
      metallothionein-transgenic (MT(trans)) mice, and in cultured human dopaminergic
      (SK-N-SH) neurons to determine the neuroprotective potential of metallothionein
      against ONOO(-)-induced neurodegeneration in Parkinson disease (PD). SIN-1
      induced lipid peroxidation, reactive oxygen species synthesis, caspase-3
      activation, and apoptosis were attenuated by metallothionein gene overexpression
      and augmented by metallothionein gene down-regulation. A progressive
      nigrostriatal dopaminergic neurodegeneration in weaver mutant (wv/wv) mice was
      associated with enhanced nitrite ion synthesis, metallothionein down-regulation,
      and significantly reduced dopamine synthesis and 18F-DOPA uptake as determined by
      high-resolution micropositron emission tomography neuroimaging. The striatal
      (18)F-DOPA uptake was significantly higher in MT(trans) mice than in MT(dko) and
      alpha-synuclein knockout (alpha-Syn(ko)) mice. These observations provide further
      evidence that nitric oxide synthase activation and ONOO- synthesis may be
      involved in the etiopathogenesis of PD, and that metallothionein gene induction
      may provide neuroprotection.

PMID- 17018884
TI  - Effects of ceramide-1-phosphate on cultured cells: dependence on dodecane in the
      vehicle.
AB  - Ceramide-1-phosphate (C1P), the product of ceramide kinase, is a
      sphingophospholipid with recently recognized signaling properties. In particular,
      it was reported to be mitogenic and capable of direct stimulation of cytosolic
      phospholipase A(2alpha). Much of the present knowledge has relied on the use of
      C1P of various acyl chain lengths, together with diverse protocols to deliver it
      to cultured cells. A mixture of ethanol (or methanol) with dodecane, as the
      vehicle, has become popular. However, the contribution of this solvent to the
      observed effects of C1P has not been documented. Here, we show that addition of
      C1P in ethanol-dodecane to culture medium leads to irreversible cytotoxic
      effects. These culminate in mitochondrial swelling, vacuole formation, and cell
      death. Not only the toxicity of C1P, but also its ability to trigger
      prostaglandin E2 release, is fully dependent upon addition of a premade C1P
      dodecane mixture. Furthermore, we show that these effects are not restricted to
      C1P. They result from the capacity of dodecane to interact with phospholipids;
      hence, they go undetected with a vehicle control. This study should raise
      awareness about the use of dodecane for phospholipid delivery and, in turn, help
      in unraveling C1P signaling, which is still poorly understood.

PMID- 17018885
TI  - Reduction of plasma triglycerides in apolipoprotein C-II transgenic mice
      overexpressing lipoprotein lipase in muscle.
AB  - LPL and its specific physiological activator, apolipoprotein C-II (apoC-II),
      regulate the hydrolysis of triglycerides (TGs) from circulating TG-rich
      lipoproteins. Previously, we developed a skeletal muscle-specific LPL transgenic
      mouse that had lower plasma TG levels. ApoC-II transgenic mice develop
      hypertriglyceridemia attributed to delayed clearance. To investigate whether
      overexpression of LPL could correct this apoC-II-induced hypertriglyceridemia,
      mice with overexpression of human apoC-II (CII) were cross-bred with mice with
      two levels of muscle-specific human LPL overexpression (LPL-L or LPL-H). Plasma
      TG levels were 319 +/- 39 mg/dl in CII mice and 39 +/- 5 mg/dl in wild-type mice.
      Compared with CII mice, apoC-II transgenic mice with the higher level of LPL
      overexpression (CIILPL-H) had a 50% reduction in plasma TG levels (P = 0.013).
      Heart LPL activity was reduced by approximately 30% in mice with the human apoC
      II transgene, which accompanied a more modest 10% decrease in total LPL protein.
      Overexpression of human LPL in skeletal muscle resulted in dose-dependent
      reduction of plasma TGs in apoC-II transgenic mice. Along with plasma apoC-II
      concentrations, heart and skeletal muscle LPL activities were predictors of
      plasma TGs. These data suggest that mice with the human apoC-II transgene may
      have alterations in the expression/activity of endogenous LPL in the heart.
      Furthermore, the decrease of LPL activity in the heart, along with the inhibitory
      effects of excess apoC-II, may contribute to the hypertriglyceridemia observed in
      apoC-II transgenic mice.

PMID- 17018886
TI  - High postprandial triglyceridemia in patients with type 2 diabetes and
      microalbuminuria.
AB  - Microalbuminuria (MA) is an independent risk factor for atherosclerosis in
      patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also
      associated with excess cardiovascular risk. However, the association between MA
      and postprandial lipemia in diabetes has not been investigated. A total of 64
      patients with T2DM, 30 with and 34 without MA, were examined. Plasma total
      triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in
      CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed
      meal. Postheparin LPL and HL activities were also determined. Plasma levels of
      apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting
      state and 2 h postprandially. Patients with MA had higher postprandial total TG
      levels than those without MA (P < 0.001); this increase been attributed mainly to
      CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins
      were not different between the studied groups, whereas HL activity was higher in
      the patients with MA. ApoC-II and apoC-III levels did not change postprandially
      in either study group, whereas apoA-V increased more in the patients with MA.
      These data demonstrate for the first time that MA is characterized by increased
      postprandial lipemia in patients with T2DM and may explain in part the excess
      cardiovascular risk in these patients.

PMID- 17018887
TI  - Treatment of stage I testicular germ-cell tumors.
AB  - More than a half of patients with testicular cancer are diagnosed with clinical
      stage I disease. In this setting, definitive cure is the rule. However, there is
      no consensus on the optimal treatment choice. A literature review (1990-2005) was
      performed in order to identify the pros and the cons associated with each
      therapy, as well as their long-term outcomes. Several treatment alternatives
      yield similar efficacy results. Thus, therapy-related morbidity, economic costs,
      quality-of-life issues, and patient preferences should be considered. Refinement
      in the knowledge of predictive factors for relapse and amounting experience with
      both surveillance and adjuvant chemotherapy have led to consideration of risk
      adapted treatment policies as an alternative to more traditional approaches
      (i.e., prophylactic irradiation for seminomas and retroperitoneal lymph node
      dissection for non-seminomas). In conclusion, with cure rates approaching 100%,
      close surveillance for low-risk patients and adjuvant chemotherapy for those at
      high risk of relapse seems the preferred option for clinical stage I testicular
      cancer, in both seminoma and non-seminoma cases.

PMID- 17018888
TI  - Focal radiation therapy of brain metastases after complete surgical resection.
AB  - Brain metastases are a frequent occurrence in cancer patients and result in
      significant morbidity and mortality. The three main treatments for brain
      metastases include surgery, radiation, and/or chemotherapy, alone or in
      combination. After resection alone, local recurrence rates are high. Whole brain
      radiation therapy can decrease the probability of recurrence; however, this has
      some disadvantages. Focal radiation therapy (FRT) may provide many of the same
      benefits without some of these disadvantages. In this study, we retrospectively
      analyzed patients with single brain metastases treated with FRT after surgery.
      Doses ranged from 14 Gy as single dose stereotactic radiosurgery (SRS) to 54 Gy
      in 27 2-Gy fractions as conformal fractionated radiotherapy. Four of the seven
      patients had a same-site recurrence, with an average time to recurrence of 115.5
      d. Median dose in the patients that had same-site recurrence was 42 Gy. One of
      these patients is currently living. Two patients did not have recurrence, and one
      patient had a recurrence at a different site within the brain. The low rate of
      out-of-field recurrences during the patients life indicates focal radiation may
      be a reasonable therapeutic alternative. Given the number of patients with same
      site recurrences, wide field margins around the tumor volume or higher radiation
      doses than those typically used in palliative regimens may be useful in post
      excisional FRT. Additionally, we found that a longer delay in the initiation of
      FRT after initial diagnosis may result in a decreased time to same-site
      recurrence. However, further studies are warranted given the small number of
      patients in this study.

PMID- 17018890
TI  - Serum and urine survivin levels in breast cancer.
AB  - This study was conducted to investigate the serum and urine levels of survivin in
      patients with breast cancer and the relationships with known prognostic
      parameters and therapy. Forty-three patients with breast cancer and 21 healthy
      control subjects were investigated. Serum samples were obtained on the first
      admission before adjuvant and metastatic treatment were given and after two
      cycles of chemotherapy. Serum and urine survivin levels were determined using
      enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA),
      respectively. There was no significant difference in the baseline serum and urine
      levels between patients with breast carcinoma and healthy controls (p = 0.19 and
      p = 0.84, respectively). None of the prognostic parameters analyzed were
      significantly correlated with the urine survivin concentrations. This was also
      true for serum survivin values, except for nodal involvement. Serum survivin
      levels were significantly higher in the patients with nodal involvement compared
      with node negatives (p = 0.043). However, serum survivin levels were not
      influenced by the number of involved nodes (p = 0.77). No significant correlation
      was found between the serum and urine levels of survivin (r = 0.15, p = 0.27).
      Serum and urine levels did not change significantly after chemotherapy (p = 0.59
      and p = 0.50, respectively). In conclusion, the result of this study suggested
      that serum survivin level could be a sensitive marker for detecting metastases in
      lymph nodes from breast cancer patients. However, much research continues in this
      field, and exciting new knowledge will ultimately emerge.

PMID- 17018889
TI  - Phase II trial of a simultaneous radiochemotherapy with cisplatinum and
      paclitaxel in combination with hyperfractionated-accelerated radiotherapy in
      locally advanced head and neck tumors.
AB  - BACKGROUND: Simultaneous radiochemotherapy (RCT) is the treatment of choice for
      locally advanced head and neck cancers. In order to evaluate the toxicity and the
      survival rates, we investigated the use of a very aggressive combination protocol
      that included cisplatinum and paclitaxel combined with hyperfractionated
      accelerated radiotherapy. The final results of the phase II study are listed
      below. METHODS: For the phase II trial 32 patients (29 male, 3 female) with
      histologically diagnosed locally advanced non-metastatic squamous cell carcinoma
      of the head and neck in stage III/IV were treated from 1999 to 2003. Radiotherapy
      was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. The
      chemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at
      doses of 20 mg/m(2) and during the entire course of treatment paclitaxel was
      administered twice a week at doses of 25 mg/m(2). RESULTS: The 5-yr overall and
      disease-free survival rates were 48% and 43%. Twenty-two (69%) patients reached a
      clinically complete response and 8 (25%) a partial response (for two of the
      patients the response rate is not known). Two (6%) patients died during the
      treatment. Seven (22%) patients developed local recurrences and six of these
      patients have in the meantime died. With regards to the four (12%) patients who
      developed distant metastases, three of them have in the meantime died and two
      (6%) patients have died as a result of secondary malignancies. Seven out of 25
      (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients
      developed grade 3 mucositis. No cases of grade 4 mucositis were observed;
      however, one patient out of 25 (4%) was classified with grade 4 dermatitis. One
      out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22 patients
      (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a
      grade 3 leukopenia, and 2 out of 25 patients (8%) experienced a grade 4
      eutropenic infection. Dysphagia was a significant late toxicity. Out of 24
      patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a
      grade 3 xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.
      CONCLUSION: This very aggressive radiochemotherapy protocol yielded excellent
      response and overall survival rates; however it is associated with a very high
      rate of acute toxicity. Therefore, in such cases where acute toxicity resulted,
      extensive supportive care is required.

PMID- 17018891
TI  - Impact of diabetes mellitus on treatment outcomes in patients with nasopharyngeal
      cancer.
AB  - BACKGROUND AND PURPOSE: To determine the influence of diabetes mellitus on stages
      and long-term outcomes among patients with nasopharyngeal cancer. MATERIAL AND
      METHODS: The study summarized 37 patients who were diagnosed as having diabetes
      mellitus and nasopharyngeal cancer and treated by radiotherapy between January
      1999 and December 1999. With a median follow-up of 34.6 mo, we analyzed
      differences in RFS, MFS, DFS, and OS between the diabetes and the non-diabetes
      group. RESULTS: 37 patients were involved in our study. According to the Chinese
      Fuzhou staging system for NPC, which was modified in 1992, 2 patients belong to
      stage I, 9 stage II, 17 stage III, and 6 stage IV. The 4-yr RFS of diabetes group
      and non-diabetes group was 52.1% vs 68.2%, the 4-yr MFS was 73.0% vs 72.0%, the 4
      yr DFS was 35.1% vs 65.1%, and the OS was 67.6% vs 75.7%. The Wilcoxon (Gehan)
      test showed there was no significant difference between the two groups of RFS,
      MFS, and OS, while the diabetes group had a worse DFS than non-diabetes group
      (Wilcoxon p = 0.0047). CONCLUSIONS: Patients with diabetes had a worse DFS than
      non-diabetes, but statistic tests did not show significant differences in RFS,
      MFS, and OS; further studies should be continue to find out the results in the
      future.

PMID- 17018892
TI  - Clinical predictors of severe toxicity in patients treated with combination
      chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer:
      a single center experience.
AB  - INTRODUCTION: Little has been published regarding clinical predictors of severe
      toxicity in patients with metastatic colorectal cancer (CRC) treated with
      combination chemotherapy (CT) with oxaliplatin and/or irinotecan. MATERIAL AND
      METHODS: We analyzed retrospectively 142 patients treated between 1996 and 2004
      in our center with these regimes with regards to grade 3-4 toxicity and overall
      survival (OS) rates. Kohne's prognostic classification could be applied in all
      patients. RESULTS: Kohne classification: good (54.2%), intermediate (26.8%), and
      poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles
      6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to
      toxicity. 50.7% suffered grade 3-4 toxicity: digestive (28.2%), hematologic
      (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic
      deaths. 70.9% of grade 3-4 episodes occurred in the first four cycles. Median
      follow-up of 33.9 mo; median OS of 15.9 mo. For Kohne classification: good (20
      mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and
      age > 70 yr predicted higher overall grade 3-4 toxicity, with no differences in
      CT efficacy; age > 70 yr and PS > 1 predicted higher grade 3-4 fatigue. No
      relationship could be found between baseline laboratory characteristics and
      higher toxicity, except baseline hemoglobin and grade 3-4 hematologic toxicity.
      CONCLUSIONS: Female and elderly patients have a higher grade 3-4 toxicity rate
      when treated with combination CT with oxaliplatin or irinotecan. Prognostic
      classifications such as Kohne's can help differentiate subgroups of patients who
      benefit little with the use of combination CT.

PMID- 17018893
TI  - High-risk fludarabine-pretreated B-cell chronic lymphocytic leukemia's high
      response rate following sequential DHAP and alemtuzumab administration though in
      absence of molecular remission.
AB  - B-CLL patients with resistant/relapsed disease or adverse prognostic factors at
      presentation are suitable for alternative treatments. In the present pilot study
      we investigated a novel intensive chemo-immunotherapy approach for high-risk,
      fludarabine pretreated patients. Ten patients with resistant/relapsed, advanced
      stage BCLL were included. Age was 37-60 yr (median 53). All but one had an
      unmutated IgVH status. The treatment schedule included debulking with two DHAP
      courses followed by alemtuzumab (30 mg, eight doses), followed by peripheral
      blood progenitor cell (PBPC) mobilization with intermediate/high-dose
      cyclophosphamide and by autografting after high-dose mitoxantrone+L-Pam. The DHAP
      alemtuzumab combination was highly effective. Eight patients out of 10 responded
      to DHAP, with a single complete remission. Following alemtuzumab, the number of
      overall responses increased to nine, and the complete remissions to five. After
      alemtuzumab PB double-positive clonal CD5+/CD19+ lymphocytes dropped, with median
      purification rate 99.95%. Owing to poor PBPC mobilization, only five patients
      underwent autografting, and three of these experienced post-graft recurrence. The
      six patients entering complete remission were free of disease 3-23 mo after study
      entry, and three of them were still in remission at 3, 7, and 22 mo. However,
      molecular evaluation regularly revealed persistence of minimal residual disease,
      both in all PBPC collections tested and in post-treatment follow-up samples. The
      use of DHAP/alemtuzumab appears useful to re-induce disease remission in
      relapsed/refractory, high-risk B-CLL patients. However, the addition of autograft
      was not usually feasible and of questionable clinical use. Other strategies
      should thus be considered for remission maintenance.

PMID- 17018894
TI  - A phase I trial of gemcitabine administered as a 96-h continuous intravenous
      infusion in patients with advanced carcinoma and lymphoma.
AB  - BACKGROUND AND OBJECTIVE: Preclinical data suggest gemcitabine may have schedule
      dependent activity favoring prolonged infusion. We sought to determine the
      recommended phase II dose (RPTD) and toxicity of gemcitabine when given as a
      continuous intravenous (CIVI) over 96 h. PATIENTS AND METHODS: Gemcitabine was
      initially given at 1 mg/m(2)/d for 48, then 72, and finally 96 h. The dose was
      then increased to 2, 4, 6, 10, 15, 20, and 25 mg/m(2)/d. Dose levels of 7, 8, 9
      mg/m(2)/d as 96-h infusion were added later after a protocol modification. After
      identifying the RPTD using an every 3-wk schedule, we then evaluated the
      feasibility of repeating the infusion every 2 wk, and then weekly for 3 of 4 wk.
      RESULTS: Thirty-four patients with a variety of tumor types received a total of
      126 cycles of therapy (median of 2 cycles, range 1-10 cycles). The RPTD was 8
      mg/m(2)/d every 3 wk, and 6 mg/m(2)/d every 2 wk. The most common grade 2 or
      higher toxicities at all dose levels (>or= grade 2) included fever (n = 14),
      dyspnea (n = 7), mucositis (n = 6), hypotension (n = 6), nausea/vomiting (n = 6),
      and fatigue (n = 5). Neutropenia and/or thrombocytopenia were uncommon.
      CONCLUSION: Administration of gemcitabine as a 96-h infusion results in a
      markedly different toxicity profile and RPTD than when given by a conventional 30
      min infusion. The RPTD was 8 mg/m(2)/d (32 mg/m(2)/course) when given every 3 wk,
      or 6 mg/m(2)/d (24 mg/m(2)/course) when given every 2 wk.

PMID- 17018895
TI  - Isolation and expansion of allogeneic myeloma-specific interferon-gamma producing
      T cells for adoptive immunotherapy.
AB  - Adoptive immunotherapy is a promising approach in the treatment of multiple
      myeloma. We have tested the identification, separation, and expansion of
      allogeneic myeloma-specific T cells in vitro. Irradiated myeloma cell line ARH 77
      has been used to stimulate allogeneic CD4(+) and CD8(+) T lymphocytes. Activated
      myeloma-specific T cells that produced interferon-gamma were isolated using
      immunomagnetic beads and further expanded in vitro to numbers of up to 400 x 106
      T cells. Specificity of the T lymphocytes was tested using a 5-(6
      )carboxyfluoresceine diacetate succinimidyl ester (CFSE)-based cytotoxicity test.
      This study demonstrates the feasibility of identification and isolation of tumor
      specific T cells from allogeneic donors that can be expanded in vitro to numbers
      useful for clinical applications.

PMID- 17018896
TI  - Immunologic abnormalities in myelodysplastic syndromes: clinical features and
      characteristics of the lymphoid population.
AB  - It has been recognized that some patients with myelodysplastic syndromes (MDS)
      develop immunologic abnormalities, but little is known of its correlations to MDS
      specific disease features. In a retrospective study of 284 MDS patients, we
      identified 32 patients (11.3%) with clinical or serologic immunological
      abnormalities (group A) and compared them to the remaining 252 cases (group B).
      Group A consisted of 20 patients with clinical signs of autoimmune disease and 12
      asymptomatic patients with serologic immunological abnormalities only. Apart from
      significant female predominance in group A (M/F = 2.5 vs M/F = 0.7, p = 0.001),
      the other clinical and biological features such as median age, distribution of
      MDS subtypes, incidence of karyotyopic abnormalities, "abnormal" in vitro growth
      of GM-progenitors and survival times were similar in the two groups. Autoimmune
      manifestations partially responded to immunosuppressive therapy, with moderate
      improvement of peripheral cytopenia. In addition, CD3(+), CD4(+), CD8(+),
      CD19(+), and CD56(+) cells were quantified in peripheral blood of 38 patients.
      Matched with similarly aged healthy control group, most MDS patients showed
      significant lymphocytopenia, mainly due to the reduction of T-helper series (in
      both absolute numbers and percentage). B-cells were reduced in absolute numbers,
      but their percentage still overlapped with the control. No major abnormalities of
      natural killer cells (CD56(+)) were seen. We conclude that autoimmune diseases
      and asymptomatic immunologic abnormalities are common in patients with MDS, but
      except for female predominance, no correlation between these abnormalities and
      MDS-specific disease features were found.

PMID- 17018897
TI  - Growth inhibition and differentiation induced by peroxisome proliferator
      activated receptor gamma ligand rosiglitazone in human melanoma cell line A375.
AB  - BACKGROUND: Ligands of peroxisome proliferator-activated receptors (PPARs) have
      been demonstrated to be antitumorgenic in vitro and in vivo due to their
      antiproliferative, prodifferential, and antiangiogenic effects. The aim of this
      study is to evaluate the effects and mechanisms of PPARgamma ligand rosiglitazone
      (ROZ) on the growth, apoptosis, and differentiation in human melanoma cancer cell
      line A375. METHODS: The effects of ROZ on A375 cell proliferation were measured
      by clonogenic assay, apoptosis and cell cycle kinetics by FACS with ROZ for 72 h,
      PPARgamma protein was detected by Western blot analysis and immunocytochemical
      staining, and PPARgamma mRNA expression by RT-PCR. The differentiation effect of
      ROZ was determined by measurement of melanin content and tyrosinase activity. The
      levels of Bcl-2, P53, p-ERK, and ERK were also detected by Western blot analysis.
      Inhibition of tumorigensis was observed in nude mice. RESULTS: ROZ inhibited
      colony formation and induced apoptosis in A375 cells, and the cells were arrested
      in G1 phase. This effect was associated with a decrease of the expression of Bcl
      2 and increase of the expression of P53. ROZ also induced the differentiation in
      A375 cells. ROZ increased expression of PPARgamma and decreased the expression of
      ERK and p-ERK. Data in vivo showed that ROZ could inhibit tumorigensis in nude
      mice. CONCLUSION: These results demonstrated that ROZ inhibited growth of A375
      cells via the induction of apoptosis, necrosis, and differentiation in a
      PPARgamma-dependent manner and might present a promising therapeutic approach in
      certain human maligancies.

PMID- 17018898
TI  - Morphologic research of microcirculation patterns in human and animal melanoma.
AB  - OBJECTIVE: The pattern and distribution of microcirculation of malignant melanoma
      were studied in human malignant melanoma tumor samples and in an animal model by
      staining of paraffin-embedded sections and transelectron microscopy. METHODS:
      Blood supply models for melanoma were studied with immunohistochemical and
      periodic acid-Schiff (PAS) double-staining technique. New sections were made from
      190 paraffin-embedded melanoma samples, and immunohistochemical staining of the
      platelet-endothelial cell adhesive molecule (CD31 antigen) and PAS staining were
      conducted to confirm different microcirculation patterns of melanoma.
      Furthermore, malignant melanoma cells B16 and LiBr were injected into the groin
      of C57 mice and into the abdominal cavity of SCID mice, respectively. Tumors with
      vasculogenic mimicry (VM) were stained with PAS and CD31 to study the morphology
      and distribution of VM in mice melanoma. A diluted suspension of activated carbon
      was injected into the circulation of mice previously inoculated in the groin with
      B16 melanoma cells. Tumor tissue with VM was observed under electron microscopy.
      RESULTS: There were three kinds of microcirculation pattern in human and animal
      melanoma. The walls of VM were positive for PAS staining and negative for CD31
      staining in the tumor tissues. The distribution of VM and mosaic vessels was not
      uniform and appeared in patches. VM along with endothelium-dependent vessels and
      mosaic vessels sustained the blood supply for the tumors. The results from
      electron microscopy validated the presence of three patterns. CONCLUSIONS: The
      results obtained using activated carbon as a tracer showed that VM and mosaic
      vessels connect with the host blood circulation. VM and mosaic vessels exist in
      malignant melanoma. Tumor cells can obtain oxygen and nutriment through VM and
      mosaic vessels besides endothelium-dependent vessels.

PMID- 17018899
TI  - Effect of ascorbic acid, lysine, proline, and green tea extract on human
      osteosarcoma cell line MNNG-HOS xenografts in nude mice: evaluation of tumor
      growth and immunohistochemistry.
AB  - Structural changes in the extracellular matrix (ECM) are necessary for cell
      migration during tissue remodeling. MMPs, VEGF, Ki-67 (proliferative protein),
      and constituents of ECM play a critical role in angiogenesis and underlie
      neoplastic invasion and metastasis. This prompted us to investigate the effect of
      a diet containing lysine, proline, arginine, ascorbic acid, and green tea extract
      (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in
      athymic nude mice and the expression of MMPs, VEGF, Ki-67 and fibronectin in
      these tumors, as well as the production of mucin (by PAS staining). We also
      investigated the effect of the supplemented diet on serum ascorbic acid, total
      protein content, alkaline phosphatase activity, and liver enzymes. Athymic male
      nude mice (n = 12) were inoculated with 3 x 10(6) osteosarcoma cells MNNG-HOS and
      randomly divided into group A (fed a regular diet) and group B (fed a regular
      diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed.
      Results showed that NM inhibited the growth and reduced the size of tumors in
      nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and
      VEGF secretion in the control group tissues. Results demonstrate that the
      nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea
      extract tested strongly suppressed the growth of tumors without adverse effects
      in nude mice, suggesting potential as an anticancer agent.

PMID- 17018900
TI  - Pemetrexed-induced acute renal failure, nephrogenic diabetes insipidus, and renal
      tubular acidosis in a patient with non-small cell lung cancer.
AB  - We report a patient with metastatic non-small cell lung cancer who developed
      renal toxicities manifest as acute renal failure associated with nephrogenic
      diabetes insipidus and distal renal tubular acidosis following sequential therapy
      with pemetrexed. The nephrotoxicity occurred concomitantly with severe
      myelosuppression. We postulate renal tubular toxicity may account for distinct
      patterns of injury including acute renal failure and tubular cell dysfunction of
      the distal nephron.

PMID- 17018901
TI  - Unusual cyclin D1 positive marginal zone lymphoma of mediastinum.
AB  - We report a case of 43-yr-old Caucasian female with an unusual, cyclin D1
      positive marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT)
      type of the mediastinum. To date, only about 30 cases of this entity have been
      published. They occur mainly in Asian females with a history of coexisting
      autoimmune disease. To our knowledge, this is the first case of mediastinal MZL
      with cyclin D1 expression. In the span of 6 yr this patient's tumor recurred
      three times, was surgically treated, and initially diagnosed as paraganglioma.
      The diagnosis was based on histopathological examination only. Our final
      diagnosis of MZL was made by combined evaluation of histopathology (HP),
      immunohistochemistry (IH), flow cytometry (FCM), fluorescence in situ
      hybridization (FISH), and molecular biology studies. We found a positive cyclin
      D1 reaction by IH and cyclin D1 mRNA (CCND1) overexpression by reverse
      transcription polymerase chain reaction (RT-PCR). Very high cyclin D1 to beta
      actin mRNA ratio in this case was comparable with the ratio, characteristic for
      mantle cell lymphoma (MCL). However, there was no translocation t(11;14) found by
      FISH and an immunophenotype by IH and FCM was consistent with MZL ruling out MCL
      diagnosis. In addition, our case differs from other, previously reported thymic
      MZL lymphoma cases by no autoimmune disease association, Caucasian origin, and
      the absence of the plasmacytic differentiation on both HP/IH.

PMID- 17018902
TI  - [New layout in a new millennium [Editorial].].

PMID- 17018903
TI  - [Neurosciences, new knowledge challenges old ideas [Editorial].].

PMID- 17018904
TI  - [Study of medications use of elderly admitted to acute care hospital.].
AB  - OBJECTIVE: The prevalence of diseases increases with age and so does use of
      medications. Thus illness related to medications use does also become more
      prevalent. This study aims at evaluating medications of elderly people admitted
      to an acute care hospital, and demonstrate adverse reactions and quality
      indicators. MATERIAL AND METHODS: This is a study of patients 75 years of age and
      older admitted acutely to internalmedicine at the Reykjavik Hospital over a three
      month period in the spring of 1995. All medications and diagnoses were registered
      and the medical records reviewed. The contribution of adverse medication effects
      to the admission was assessed. Quality of treatment was evaluated according to
      evidence based medicine for the diagnoses chosen. The study included 208
      individuals, 133 women and 75 men with the mean age of 82.4 years. RESULTS: Mean
      length of stay for women was 19.9 days and men 15.2 days. Number of drugs on
      admission and discharge ranged from 0 to 18. The mean number of drugs were for
      women 5.8 and 6.9 and men 6.6 and 7.7 on admission and discharge, respectively.
      In 16 cases or 7.7% it was judged that there was a high likelihood of the
      admission being due to an adverse effect. Potential drug interactions according
      to a computer software package were not judged to be of clinical importance in
      any case. CONCLUSIONS: Treatment for coronary heart disease, heart failure,
      osteoporosis, insomnia and long term prednisolon treatment is not completely
      optimal according to evidence based medicine. The results of this study indicate
      that treatment could be improved for example with use of clinical guidelines.

PMID- 17018905
TI  - [Deep vein thrombosis incidence at Akureyri Hospital, Iceland 1975-1990. Long
      term prognosis.].
AB  - OBJECTIVE: To evaluate the incidence of deep vein thrombosis (DVT) in a rural
      area of Iceland and the prevalence of post thrombotic syndrome (PTS) in patients
      with history of DVT. MATERIAL AND METHODS: A retrospective study where all
      phlebographies (n=177) performed at the department of radiology, Akureyri
      Hospital, during the period 1975-1990 were re-evaluated. Information on patients
      with DVT (n=32) were taken both from the Hospital and the Health Center records.
      All patients alive in December 1997 (n=17), 10.5 years after the diagnosis of DVT
      were interviewed concerning PTS. RESULTS: The incidence of DVT during the period
      1975-1990 was 1/10,000 inhabitants/year, but was 2.3/10,000/ year for the period
      1986-1996. The mean age was 60 years and 62% of the patients were males. In 37.5%
      cases DVT was localized below the popliteal vein, in another 34.4% below the
      inguinal ligament and 28.1% of the thrombosis extended to the pelvic vein system.
      Of the patients 23.3% had a history of malignancy and 20% had undergone a major
      operation or had trauma. Of the patients 46.7% were smokers. At 10.5 years follow
      up, 71% of the patients had some problems due to PTS, and these symptoms
      influenced significantly their quality of daily life. CONCLUSIONS: The prevalence
      of DVT in Iceland seems to be only half of what foreign studies suggest and
      patients with history of DVT suffer frequently from PTS 10 years after the DVT.
      These data indicate that it is necessary to improve the long term treatment of
      patients with history of DVT.

PMID- 17018906
TI  - [Head injury at Reykjavik Hospital, intensive care unit, 1994-1998.].
AB  - OBJECTIVE: Reykjavik Hospital is the main trauma hospital in Iceland, receiving
      all severe head injuries in the country. Incidence of head injury and mortality
      has been decreasing in the last decades. The aim of this study was to analyse
      data on admission, treatment and outcome of patients admitted to intensive care
      unit with severe head injury and compare with other countries. MATERIAL AND
      METHODS: In this study we looked retrospectively at the incidence of severe head
      injuries admitted to the intensive care unit at Reykjavik Hospital 1994-1998.
      Number of patients, type of injury, length of stay, length of ventilator
      treatment. Glasgow Coma Score (GCS), APACHE II (Acute Physiologic and Chronic
      Health Evaluation) score and mortality was analysed. RESULTS: A total of 236
      patients was admitted with an average of 47 patients per year. Traffic accidents
      were the most common cause of injury and mortality was 11.7%. Ethanol consumption
      was seen in many cases where fall was the cause of accident, most often in the
      year 1998 in 75% of cases. Mortality of patients with GCS 8 that was 40% of the
      patients was must higher or 24.7% compared with patients with GCS >8 where
      mortality was 3.4%. There was an increase in admissions in 1998, with more severe
      injuries and significantly longer length of stay and ventilator treatment.
      CONCLUSIONS: Number of patients with head injury was decreasing in comparison
      with older studies. The results of treatment are rather good in comparison with
      other countries with relatively low mortality, or 11.7% versus 15-20% in nearby
      countries. There has been improvement of outcome in patients with the most severe
      head injury (GCS 8) since 20 years ago, where up to 50% of the patients died but
      in our study mortality was 24.7%. Alcohol consumption was seen in 46% of cases
      where fall was the cause of head injury. Those that suffer head trauma are most
      often young people and preventive measures must continue with full strength in
      order to decrease the incidence of accidents in our society.

PMID- 17018907
TI  - [Cancer Incidence among Female Manual Workers.].
AB  - We investigated cancer incidence during the period 1970-1992 among unskilled
      Icelandic female workers who contributed to two pension funds for manual workers.
      We found an increase in the standardized rate ratios (SRRs) for all cancer with
      increasing time before the follow-up period began. We found no clear relation
      between cancer incidence and length of employment. The SRRs were higher for those
      who became members of the funds in 1977 or later than for those who started
      earlier: among these women we found SRRs for all cancers, 1.36; cancer of the
      stomach, 1.49; cancer of the lung, 1.48; cancer of the cervix, 3.19; and cancer
      of the bladder, 6.00.

PMID- 17018908
TI  - [The first 10 years of operation of the Red Cross House for runaway, throwaway
      and homeless adolescents in Reykjavik, Iceland.].
AB  - OBJECTIVE: The Red Cross House (RCH) is a 24-hour emergency shelter in Reykjavik,
      Iceland for adolescents. On the occasion of its 10th anniversary it was decided
      to analyse the data collected since inauguration. MATERIAL AND METHODS: During
      the first 10 years of running 475 adolescents, age 10-18, (grouped into runaways,
      throwaways and homeless adolescents) registered 927 visits. The admission records
      of the RCH were used for collecting data for subsequent analysis. RESULTS: The
      runaways and throwaways were more alike one another than the homeless. Most of
      the parents were living apart suggesting that conflicts were more likely to take
      place in stepfamilies and single parent families and the situation at home had
      enforced one parent to leave home. Many of the guests were school-dropouts
      particularly those coming from the country. A majority had been in contact with
      the social services, and many boys had been dealt with by the police. Prior use
      of alcohol, tobacco and drugs was common. Conflicts within the family was the
      most usual reason for the runaways and throwaways seeking assistance. The most
      common reason for the homeless visiting was having nowhere to stay, alcohol or
      drug abuse. CONCLUSIONS: The plight of the homeless was more serious than that of
      the runaways and throwaways. The homeless usually had a prior history of having
      run away or been throwaways from home. The preventive work of the RCH is
      reflected in keeping young people off the streets and offering assistance before
      it is too late.

PMID- 17018910
TI  - [Protection of Privacy and the ethics of science [Editorial].].

PMID- 17018909
TI  - [Death and dying - definition and determination.].
AB  - For the first half of this century there was no major dispute over the criteria
      for death. This was to change dramatically with major technological breakthroughs
      in modern medicine starting with the advent of the respirators. The consequences
      of their use raised serious questions about the traditional ways of diagnosing
      death. Today there are two different philosophical positions about what it means
      to be dead in terms of brain functions: One, which is not currently law in any
      jurisdiction, would pronounce a person dead when there is an irreversible loss of
      higher brain functions. This has been called cognitive death. The patient is not
      in a coma, because arousal mechanisms are present, the brain stem functions being
      relatively intact. The other philosophical position considers a person dead if
      there is an irreversible loss of the functions of the brain stem or the entire
      brain. The neurologic syndrome of brain death has been accepted by the medical
      profession as a distinct clinical entity that experienced physicians can diagnose
      with an extremely high degree of certainty, and can usually easily be
      distinguished from other neurologic syndromes. However, we must not lose sight of
      the fact that this is less a conclusion than a beginning. It is the task of
      philosophy to offer analyses of personhood and of personal identity that might
      support practical formulations for the determination of death and theology has
      reflected upon the meaning of death, if not its definition, from time immemorial.
      To define the death of a human being we must recognize the characteristics that
      are essential to humaneness. It is quite inadequate to limit the discussion to
      the death of the heart or the brain.

PMID- 17018911
TI  - [Educational level and coronary heart disease [Editorial].].

PMID- 17018912
TI  - [In search for explanatory factors in the relationship between educational level
      and mortality.].
AB  - OBJECTIVE: The connection between socioeconomic status and mortality is well
      known in Western countries. Educational level has frequently been used as a
      socioeconomic indicator. In a recent Icelandic prospective study, an inverse
      relationship between educational level and mortality was shown. The objective of
      the present study is to consider possible explanatory factors. MATERIAL AND
      METHODS: This study was a part of the Reykjavik Study. A stratified sample of 400
      people was taken from one of six study groups. The sample was equally divided
      between the sexes and four educational levels. Mean age of the sample was 72.7
      years. Participants completed a questionnaire concerning knowledge of risk
      factors for coronary heart disease, expected response to symptoms of cardiac
      infarction, social network and use of health care. Response rate was 78.5%. The
      relationship between answers and educational level was assessed with logistic
      regression. RESULTS: People with higher education were more likely to be in
      personal contact with nurses and doctors and receive advice concerning health and
      treatment from them. Participants were generally satisfied with the Icelandic
      health care system and seemed generally to have good access to it. A relationship
      with educational level was not shown. A larger proportion of those with lower
      education had regular communication with their general practician. CONCLUSIONS:
      Our results suggest that certain health care services are integrated into the
      social network of those with higher education. This may lower their morbidity and
      mortality. Other hypotheses concerning possible explanatory factors for
      differences in health were not supported.

PMID- 17018913
TI  - [Allergy and asthma in Icelandic children - an epidemiological study.].
AB  - OBJECTIVE: The prevalence of allergy and asthma is increasing in Western
      industrialized countries. The etiology of allergy is multifactorial and only
      partly understood. In an effort to gather information about asthma and allergy in
      the pediatric population in Iceland, we have evaluated on a regular basis a
      cohort of randomly selected children born in 1987. MATERIAL AND METHODS: The
      first part of the study included 179 children at the age of 18-23 months (mean
      age 20 months). Of these, 161 children were re-evaluated at four years of age and
      134 at eight years. The evaluation included a standardized questionnaire,
      clinical examination and skin-prick tests. Asthma, eczema, allergic
      rhinoconjunctivitis and food allergy were diagnosed according to established
      criteria. RESULTS: At 20 months of age 42% of the children were diagnosed with
      asthma or allergic disorders, 45% at four years and 34% at the age of eight
      years. Initially asthma and eczema were most common, but the prevalence and
      severity of eczema had decreased at four years of age and the prevalence of
      asthma decreased between four and eight years. No child was diagnosed with
      allergic rhinoconjunctivitis before two years of age but 7% of four year olds and
      10% at the age of eight years. A quarter of the children had at some stage
      symptoms compatible with more than one allergic disorder. Two-thirds of the
      children who were diagnosed with eczema and/or asthma before two years of age,
      were symptom free at eight years. Thirty-eight percent of eight year old children
      with allergic symptoms had positive skin-prick tests to the allergens used, most
      commonly to cats. Seventy three percent of eight year old children with allergy
      and/or asthma, had a first degree relative with a history of allergies.
      CONCLUSIONS: As in other Western industrialized societies asthma and allergic
      disorders are common health problems amongst children in Iceland. However, the
      majority of children with allergic manifestations during the first two years of
      life, became symptom free before the age of eight years. Conversely, 50% of eight
      year olds with asthma or allergies were symptom free during the first two years
      of their life. This suggests that the mechanisms causing allergic symptoms may
      not be uniform in different age groups.

PMID- 17018914
TI  - [Predictors of mammography adherence among Icelandic women.].
AB  - OBJECTIVE: In Iceland, breast cancer is a second only to lung cancer as a cause
      of women s cancer related deaths. Despite the widely-recognized utility of
      mammography for detecting breast cancer at early stages when it is most curable,
      many Icelandic women do not adhere to mammography screening recommendations. The
      aim of the present population-based study was to identify factors that facilitate
      and hinder women s adherence to mammography screening in Iceland. MATERIAL AND
      METHODS: A randomly selected sample of Icelandic women between the ages of 40-69
      years, not previously diagnosed with breast cancer (n=1000), were recruited to
      the study by mail. Participants (n=619) completed questionnaires assessing:
      demopgraphic variables, knowledge of screening guidelines, possible facilitators
      (e.g., physician recommendation) and barriers (e.g. concern about radiation) to
      adherence, as well as stages of mammography screening adoption (precontemplation,
      contemplation, action and maintenance). RESULTS: Women in the precontemplation
      stage were more afraid of radiation than women on other stages. They as well as
      women on contemplation stage were more afraid that mammography would be painful,
      and less satisfied with previous service at the mammography screening center.
      Doctors recommendations, as well as women s knowledge about mammography screening
      guidelines, were positively related to mammography adherence. CONCLUSIONS: These
      findings suggest that physicians may have an important role in motivating women
      to follow mammography screening recommendations. Educating women about
      mammography screening guidelines and addressing their concern about radiation and
      pain may increase mammography adherence further. Service at the mammography
      screening center may also improve adherence.

PMID- 17018915
TI  - [Increase in musculo-skeletal symptoms of upper limbs among women after the
      introduction of the flow-line in the fish-fillet plants.].
AB  - OBJECTIVES: An earlier study of workers in fish-fillet plants in Iceland showed
      higher prevalence of musculoskeletal symptoms as compared to a random sample of
      the Icelandic population. Since that study a new manufacturing process, the flow
      line, has been introduced. The aim of this study was to evaluate whether this new
      work situation changed the prevalence of musculoskeletal symptoms among the
      workers of the fish-fillet plants. MATERIAL AND METHODS: The same standardised
      Nordic Questionnaire was used in both surveys. RESULTS: The monotony and the
      repetitiveness of the work increased with the new technique. The results showed
      that women had higher prevalence of symptoms of the upper limbs when working at
      the flow-line than before. The Mantel-Haenszel odds ratio for symptoms of elbows,
      fingers and wrists during the last seven days prior to the study was 2.1 (95%
      confidence interval (CI) 1.0-4.4), 1.9 (95% CI 1.1-3.2) and 1.7 (95% CI 1.0-2.7).
      The odds ratio for knees and ankles was less than one. CONCLUSIONS: The higher
      prevalence of symptoms of the upper limbs seems to be causally related to the
      increase of monotonous and repetitive work in the fish industry.

PMID- 17018916
TI  - [Musculoskeletal symptoms among female workers in fish-fillet plant who ceased or
      continued working.].
AB  - OBJECTIVE: An earlier study of workers in fish-filleting plants in Iceland showed
      high prevalence of musculoskeletal symptoms. The prevalence of symptoms of the
      upper limbs is higher after introduction of the flow-line since the women have a
      longer duration with repetitive tasks. The overall aim of this study was to
      compare the prevalence of musculoskeletal symptoms among women working at the
      flow-line with symptoms among those who had ceased to work there and to throw
      some light on the selection process of workers from this industry. MATERIAL AND
      METHODS: The standardised Nordic Questionnaire was used. Lists of names and
      addresses of the plant workers were obtained from plant management.
      Questionnaires were mailed to the home addresses of the workers. The overall
      participation rate was 71%. Two hundred eighty two women aged 16-54 answered
      where 28 women had left the plants after answering the questionnaires and 254
      were still working there. The Mantel-Haenszel test was used and stratified by age
      and odds ratio and 95% confidence intervals (CI) calculated. RESULTS: The
      prevalence of musculoskeletal symptoms during the previous 12 months was higher
      among former than current workers. The Mantel-Haenszel odds ratio for symptoms of
      the fingers, ankles and wrists hindering normal work during the previous 12
      months prior to the study was 7.1 (95% CI 2.8-18.0), 5.3 (95% CI 1.3-21.5) and
      3.4 (95% CI 1.3-8.8) respectively. CONCLUSIONS: The selection process of workers
      from the fish-processing plants may be determined by the high prevalence of
      musculoskeletal symptoms, a healthy worker selection. There may be a causal
      relationship between musculoskeletal symptoms and ceasing to work at fish
      processing plants.

PMID- 17018917
TI  - [No union on Database Research in the health sector [Editorial].].

PMID- 17018918
TI  - [Androgen insensitivity [Editorial].].

PMID- 17018919
TI  - [Complete androgen insensitivity in an Icelandic family caused by mutation in the
      steroid binding region of the androgen receptor.].
AB  - INTRODUCTION: Androgen insensitivity syndrome (AIS) is a X-linked rescessive
      disorder characterized by impairment of the androgen-dependant male sexual
      differentiation. The cause of AIS is in most cases a mutation in the gene of the
      androgen receptor on the X chromosome. In this study we describe an Icelandic
      family with two girls with AIS. A search for mutations in the androgen receptor
      gene was performed in order to identify the genetical and molecular basis for AIS
      in this family. MATERIAL AND METHODS: Genomic DNA was isolated from two girls
      with complete AIS and their close relatives. PCR was used to amplify all eight
      exons of the androgen receptor gene of the two AIS girls and SSCP used to screen
      for mutations. DNA fragments showing abnormal SSCP pattern were subjected to
      nucleotide sequencing. PCR based diagnostic method was developed and used to
      detect the mutation causing AIS in the family. RESULTS AND CONCLUSIONS: Using
      SSCP and DNA sequencing a CGA to CAA missense mutation in exon 5 at codon 752 was
      identified. The mutation causes in an Arg to Gln amino acid substitution (R752Q
      mutation) in the ligand binding domain of the androgen receptor and a complete
      androgen insensitivity. Members of the family were genotyped using a PCR based
      method for identification of the mutant allele. The results strongly indicated a
      de novo mutation in a germ cell of the maternal grandmother, as the mutation was
      not found in her blood leucocytes. The diagnostic test provided a basis for
      genetic counselling for the family.

PMID- 17018920
TI  - [Diseases in the esophagus, stomach and duodenum: is Helicobacter pylori to
      blame?].
AB  - OBJECTIVE: To evaluate a) how many of symptomatic patients referred for upper
      endoscopy have active H. pylori infection, b) the correlation between the
      indications for upper endoscopy and endoscopic diagnosis and c) the association
      between H. pylori and organic disease in the upper gastrointestinal tract.
      MATERIAL AND METHODS: This is a prospective study on 562 symptomatic patients
      referred for upper gastrointestinal endoscopy. The criteria for inclusion were
      symptoms from the upper gastrointestinal tract but patients taking
      anticoagulation medication were excluded. All patients who had received H. pylori
      eradication therapy were excluded from the final analysis. Biopsies were obtained
      from both the antrum and body of the stomach for CLO testing as well as for
      histological evaluation for H. pylori. RESULTS: For final analysis 458 patients
      (81.5%) were evaluable, 76 patients (13.5%) were excluded who came for evaluation
      after H. pylori eradication and 28 patients (5%) were also excluded due to
      inadequate information. Of 458 patients, 220 (48%) tested CLO positive, there of
      122 women (46%) and 98 men (50.5%). The correlation between indication for
      referral for upper endoscopy and final endoscopic diagnosis was poor, where
      peptic ulcer disease was clearly overrated. Active H. pylori infection was most
      often diagnosed among patients with peptic ulcer disease, particularly duodenal
      ulcer (82%) and less often gastric ulcer (60%). Patients with gastritis and
      duodenitis had H. pylori diagnosed in 57% of the cases. CONCLUSIONS: H. pylori
      was diagnosed in 48% of patients with symptoms from the upper gastrointestinal
      tract. Of all patients with peptic ulcer disease H. pylori was diagnosed in only
      69% of the cases, which is lower than previous studies have indicated. The
      correlation between indication for endoscopy and the endoscopic diagnoses is
      rather poor. It is important to perform diagnostic endoscopy early in order to
      select the best initial treatment for the patient.

PMID- 17018921
TI  - [Deaths attributable to anesthesia: a survey in Icelandic hospitals.].
AB  - OBJECTIVE: During the past 50 years many studies have been carried out to
      investigate deaths attributable to anesthesia. It can by difficult to interpret
      and compare the outcome as studies differ considerably in the methodology
      employed. However the trend seems to be that anesthetic mortality has indeed
      decreased over the years. No investigation of this kind is known to have taken
      place in Iceland. Therefore it was decided to conduct a survey in Icelandic
      hospitals in order to make comparison with these studies in other countries.
      MATERIAL AND METHODS: This prospective survey was carried out in Icelandic
      hospitals during the five year period from 1992 to 1996. A letter was sent to all
      anesthesiologists in the country and also other health care professionals known
      to administer anesthesia. The purpose and the protocol were explained. At each
      year during the study period the chairmen of the departments of anesthesiology in
      the larger hospitals and those who administered anesthesia in the smaller
      hospitals were contacted in order to seek information as to whether any deaths
      due to anesthesia had taken place during the year and the number of anesthesias
      performed. The chief anesthesia nurses in the larger hospitals as well as the
      operating room nurses in other hospitals were asked if they were aware of any
      such deaths. The Directorate of Health was contacted to find out if any
      complaints had been filed during this period related to deaths under anesthesia.
      RESULTS: No reports of deaths came from individuals. There were 14 hospitals
      which proveded information. During the study period 134,762 anesthesias were
      performed. No death was considered to be caused directly by anesthesia. No
      complaints related to anesthetic deaths were filed with the Directorate of
      Health. CONCLUSIONS: This study documents a low anesthetic mortality and compares
      favorably with results in other countries.

PMID- 17018922
TI  - [The annual meeting of the icelandic surgical society and the icelandic society
      of anestiologists [Editorial].].

PMID- 17018923
TI  - [Primary percutaneous coronary intervention (PCI) or thrombolysis in acute
      myocardial infarction [Editorial].].

PMID- 17018924
TI  - [Results of percutaneous coronary interventions in Iceland during 1987-1998.].
AB  - PURPOSE: To evaluate potential changes in clinical indications and the
      composition of the patient population undergoing percutaneous coronary
      intervention (PCI) in Iceland from 1987 to 1998. Furthermore, to assess changes
      in success rate and major complications for the procedure during the study
      interval in a small nation with one PCI centre. MATERIAL AND METHODS: The first
      PCI was performed in Iceland in May 1987. A registry has been kept from the start
      that includes clinical and procedural data, and records of complications and
      mortality. During the study interval a total of 2440 PCIs were performed. The
      annual procedure rate was low at first, with a steep rise during the last years.
      Based on procedural changes over the years the study interval was divided into
      three periods: I. 1987-1992 (471 procedures); the learning years, II. 1993-1995
      (796 procedures); increasing number of PCIs and the method established, III. 1996
      1998 (1173 procedures); increasing use of stents and new antiplatelet regime
      used. RESULTS: From period I to III, the rate of elective PCI declined from 82%
      to 52% (p<0.001), subacute procedures increased from 14% to 44% (p<0.001), acute
      PCI from 0.8% to 3% (p<0.05), and ad hoc procedures from 0.4% to 28% (p<0.001).
      This reflects an increase in PCI on patients with acute coronary syndromes, as
      the ratio of patiens with unstable angina increased from 15% to 36% (p<0.001).
      Also, 1-vessel PCI decreased proportionally from 93% to 83%, while 2 and 3 vessel
      procedures increased from 7% to 17% (p<0.001). The proportion of patients 70
      years or older increased from 7% to 27% (p<0.001). Still, the success rate for
      PCI increased from 83% to 93% (p<0.001) and the use of stents rose sharply from
      0% to 56%. The ratio of PCI due to restenosis declined somewhat between period II
      and III, from 15% to 12% (p=0.06). Simultaneously, the rate of acute coronary
      bypass surgery after PCI decreased from 4.2% to 0.2% (p<0.001) and significantly
      fewer patients had elevated creatinine kinase levels (4.0% vs 2.7%, respectively,
      p<0.05). However, clinical acute myocardial infarction after PCI remained similar
      at 1.3% and 0.9%, and the in hospital mortality was 0.6% and 0.4%. CONCLUSIONS:
      On a national basis the rate of PCI in Iceland is amongst the highest in Europe.
      Thus, in 1998, when the population in Iceland was 275,000, 453 PCIs were done
      (1647 procedures per million inhabitants). An increased number of subacute and
      acute PCIs is carried out, more complicated procedures are performed in patients
      with widespread disease, and the patient population is growing older. Still, the
      success rate is high and the frequency of complications and mortality relatively
      low.

PMID- 17018925
TI  - [Health-related quality of life among Icelanders.].
AB  - OBJECTIVE: To study health-related quality of life (HRQL) among adults in Iceland
      with a generic Icelandic instrument, IQL (Icelandic Quality of Life), if it is
      the same among men and women, and if it changes by increasing age. Furthermore,
      it was intended to find norms for men and women in different age groups in order
      to evaluate patients' deviation in HRQL. MATERIAL AND METHODS: IQL was sent to
      2800 individuals, a random sample from the national registry, stratified by sex
      in 10 years age groups from 20-79 years and those above 80 years. For each sub
      scale on the instrument and for the combined instrument raw scores were
      calculated for men and women in the age groups 20-49 years, 50-69 years and 70
      years and older which were converted to a T-score. RESULTS: The response rate was
      61%, lower among the youngest (20-29 years) as well as among the oldest (80 years
      and older), but similar for men and women. Internal missing values were few.
      Reliability of the test was good (Cronbach's alfa=0.91). HRQL among women in
      general was worse than that of men both in general as well as on most sub-scales.
      HRQL decreases with advancing age, however, with certain exceptions. A marked
      difference was found between the youngest and the oldest. The quality of life in
      the oldest group is worse than among the younger, both in general and on most sub
      scales except finance and anxiety. Depression and social function do not change
      significantly with age. The oldest are especially worse on the scales general
      health, energy and physical health. Sleep becomes worse with increasing age,
      especially among women. Five factors explain two thirds of the variance, general
      health (23.4%), mental wellbeing (20.5%), satisfaction (9.0%), sleep (6.9%) and
      finance (6.3%). CONCLUSIONS: When evaluating HRQL among patients it is necessary
      for health-care providers and researchers to take into consideration the
      difference in HRQL between men and women and the changes occurring with age.

PMID- 17018926
TI  - [Icelandic cancer research and clinical genomics [Editorial].].

PMID- 17018927
TI  - [How dangerous is indirect smoking? [Editorial].].

PMID- 17018928
TI  - [Medication use and treatment characteristics of children referred to the
      outpatient ADHD-clinic at the Department of Child and Adolescent Psychiatry, the
      National University Hospital.].
AB  - MATERIAL AND METHODS: Data was accumulated by retrospectively looking at the
      records of 102 children of both sexes between 3 and 15 years of age, referred to
      the ADHD outpatient clinic during the period June 1, 1998 - May 31, 1999. A semi
      structured diagnostic parent interview was used to assess childhood psychiatric
      disorders according to ICD-10. The ADHD Rating Scale- IV, the Home Situations
      Questionnaire and the Child Behavior Checklist were completed by the parents.
      Teachers filled out the ADHD Rating Scale and the Teacher Report Form as well as
      a form evaluating the child's academic progress. To assess intellectual
      functioning, WISC-III or WPPSI-R were administered. Medical evaluation was
      performed and drug treatment recorded. RESULTS: Seventy-two children fulfilled
      ICD-10 diagnostic criteria of hyperkinetic disorder. High rates of other
      behavioural disorders, especially oppositional defiant disorder and a significant
      frequency of emotional disorders were recorded. Nearly two-thirds of the children
      had been started on medication prior to referral, most often amytryptiline and
      methylphenidate. Eleven children received combined pharmacotherapy but 35% had
      not received any drug treatment. Psychopharmacotherapy for most of the children
      was started between the age of four and eight years. Behaviour management
      counselling and parent training was recommended in most cases. CONCLUSIONS:
      Thirty children did not meet full hyperkinetic disorder diagnostic criteria, but
      these children may nonetheless have manifested high levels of symptoms. Most of
      the children were started on tricyclic antidepressants rather than stimulants
      which is unusual compared with international research and practice. The reason is
      unclear but may reflect the high rate of comorbidity but also doctors'
      preferences.

PMID- 17018929
TI  - [Validation of an Icelandic version of the Geriatric Depression Scale (GDS).].
AB  - OBJECTIVE: The GDS is a widely used tool world wide, both in clinical practice
      and in research of the elderly. The objective was to translate and validate the
      Geriatric Depression Scale (GDS) in Iceland. The short version of the GDS was
      also studied. MATERIAL AND METHODS: GDS was translated from English to Icelandic
      and backtranslated. Individuals, both hospitalised and healthy, born 1933 or
      before were included in the study. Those who had MMSE (Mini Mental State
      Examination) score under 23 were excluded. Seventy-one individuals were examined
      for depression both with a structured interview, Composite International
      Diagnostic Interview; 1993 (CIDI-a) and with the GDS. RESULTS: The GDS results
      were comparable to the results from the interview. The cutoff score for
      depression was chosen 13/14 according to the most favorable values of sensitivity
      (0.77), specificity (0.95), positive predictive value (0.77) and kappa (0.72).
      One cutoff was chosen because in our study there were persons with moderate or
      severe depression but no one with mild depression was detected. Our cutoff score
      for depression was identical with the cutoff score in the original american GDS
      version, but the original american version included a cutoff for mild depression
      also. CONCLUSIONS: The Icelandic GDS is a reliable method to screen for
      depression among the elderly. We conclude that GDS is an useful tool in
      unravelling depressive illness amongst the elderly although not diagnostic per
      se.

PMID- 17018930
TI  - [New aspects in medical education [Editorial].].

PMID- 17018931
TI  - [Psychiatric services for children and adolescents [editorial].].

PMID- 17018932
TI  - [Hyperkinetic disorder. A review.].
AB  - Attention-deficit/hyperactivity disorder or hyperkinetic disorder is a clinically
      defined syndrome characterised by age inappropriate deficits in sustained
      attention, impulsivity and overactivity. Despite extensive investigation, a
      specific neuroanatomical, physiological, biochemical, or psychological origin has
      not been identified. Diagnosis is based on detailed medical and developmental
      history, symptom rating scales, psychological assessment and medical evaluation.
      Increases in diagnosis and treatment of the disorder have elicited public and
      professional concern. The main focus in this article is on this disorder in
      children and adolescents and includes practical information on assessment and
      treatment. Other disorders, which may be either comorbid with or mistaken for
      hyperkinetic disorder, are reviewed in less detail.

PMID- 17018933
TI  - [Validation of an Icelandic version of the Geriatric Depression Scale (GDS).].
AB  - OBJECTIVE: Health-related quality of life (HRQL) is increasingly used to estimate
      needs for medical treatment, to evaluate its outcome and quality of care. The aim
      of this study was to compare the HRQL of several diagnostic groups before and
      after treatment with the HL-test (HL = IQL, Icelandic Quality of Life test) and
      to study its validity for measuring changes in quality of life. MATERIAL AND
      METHODS: Patients on waiting lists for coronary catheterization, orthopedic or
      urologic operations, patients in psychiatric out-patient treatment and patients
      entering treatment for alcohol dependence were asked to fill in the HL-test, a
      total of 1195 patients. Three months after treatment they were retested. The
      results of tests were standarized with population norms available to make them
      directly comparable with those of the general population. RESULTS: The response
      rate was 75% in each round. The HRQL of all patients was reduced in all aspects
      compared to that of the general population, that of the heart and urology
      patients less so than that of the orthopedic and psychiatric patients. Each group
      had a specific profile, especially marked for the orthopedic and psychiatric
      patients. Following treatment the HRQL or some aspects of it improved in all
      groups, especially for those which it had been most impaired. CONCLUSIONS:
      Studies of HRQL provide information useful for planning and delivery of health
      services. The HL-test is an instrument with good validity and reliability which
      is easy to use for such studies.

PMID- 17018934
TI  - [The surgical microscope and its use in neurological surgery.].
AB  - This is a short history of glasses, telescopes and microscopes and how the
      surgical microscope developed from these optical instruments and became one of
      the most necessary and most widely used surgical instruments in the world for the
      past 30 years. It has been of great importance to modern surgery, especially ear,
      nose and throat surgery, eye surgery and last but not least neurological surgery.
      The role of the surgical microscope in Iceland, and especially in neurological
      surgery, is discussed.

PMID- 17018935
TI  - [Giant cell tumor in the whiplash. A case report.].

PMID- 17018936
TI  - [Contemplations following the Southern Iceland earthquakes [Editorial].].

PMID- 17018937
TI  - [Melanoma and dysplastic nevi. The dark side of tanning beds [Editorial].].

PMID- 17018938
TI  - [Survival and trends of ocurrence of left ventricular hypertrophy, gender
      differences during 1967-1992. The Reykjavik Study.].
AB  - OBJECTIVE: We estimated the prevalence and incidence of left ventricular
      hypertrophy (LVH) in this large prospective cohort study of almost 20,000
      participants and identified risk factors in them. Predictive factors of its
      appearance were evaluated along with morbidity and mortality calculations.
      MATERIAL AND METHODS: LVH was defined as Minnesota Code 310 on ECG. Everyone with
      this code at first visit was defined as a prevalence case and those who developed
      it between subsequent visits were incidence cases. Risk factors at the time of
      the diagnosis of LVH were determined with logistic regression. Predictive factors
      for acquiring this ECG abnormality were determined by Poisson regression. The
      comparison cohort were all other participants in the Reykjavik Study stages I-V.
      RESULTS: Two hundred ninety-seven men and 49 women were found to have LVH or 3.2%
      and 0.5%, respectively. The incidence was 25/1000/year among men and 6/1000/ year
      among women. Prevalence in both genders increased with increasing age. Risk
      factors at the time of diagnosis were systolic blood pressure (odds ratio pr.
      mmHg (OR) 1.02; 95% confidence interval (CI): 1.01-1.03), age (OR pr. year: 1.04;
      95% CI: 1.02-1.05), silent myocardial infarction (MI) (OR: 3.18; 95% CI: 1.39
      7.27) and ST-T changes (OR: 3.06; 95% CI: 2.14-4.38) among men and systolic blood
      pressure and age for women with similar odds ratio. Predictive factors for
      acquiring LVH were systolic blood pressure (incidence ratio (IR): 1.01; 95% CI:
      1.01-1.02) and angina with ECG changes (IR: 2.33; 95% CI: 1.08-5.02) among men
      and systolic blood pressure among women (IR: 1.03; 95% CI: 1.01-1.04). In men
      severe smoking seemed to have a protective effect against developing LVH (IR:
      0.36; 95% CI: 0.18-0.71). The risk for coronary mortality was significantly
      increased among women with hypertrophy (hazard ratio (HR): 3.07; 95% CI: 1.5
      6.31) and their total survival was poorer with increasing time from diagnosis of
      LVH (HR: 2.17; 95% CI: 1.36-3.48). CONCLUSIONS: We conclude that the presence of
      LVH and its appearance is associated with age and increased blood pressure among
      both genders. Women with LVH have poorer survival than other women and they are
      at threefold risk of dying of ischemic heart disease. This could indicate that
      criteria for detecting LVH on ECG detect both mild and severe hypertrophy among
      men but only the severe hypertrophy cases among women. More sensitive ECG methods
      may have to be used to detect mild, moderate and severe LVH among both genders in
      order to differentiate the severity of LVH based on the ECG diagnosis.

PMID- 17018939
TI  - [The effect of pregnancy on the survival of women diagnosed with breast cancer.].
AB  - OBJECTIVE: To answer the question whether the prognosis of women with breast
      cancer is affected by pregnancy after diagnosis. MATERIAL AND METHODS: We used
      information from the Icelandic Cancer Registry, the Birth Registry and the
      Genetic Committee. We identified all women who were diagnosed with breast cancer
      in the years 1927-1992 and who later became pregnant. Controls were women without
      a history of childbirth after diagnosis of breast cancer. They were matched on
      tumour size, axillary lymph node status and years of birth and diagnosis, with
      four year deviation. RESULTS: In the years 1927-1992, 838 women at ages below 50
      were diagnosed with breast cancer in Iceland. Of those, 29 gave birth to a child
      after the diagnosis. Fourteen cases and 33 matched controls fulfilled the
      inclusion criteria of the study. Survival was better in the group of women who
      became pregnant after diagnosis, but the difference was not statistically
      significant (P=0.06). DISCUSSION: Our results do not indicate that the prognosis
      of women who become pregnant after the diagnosis of breast cancer is worse than
      of those who do not become pregnant. The group was too small to make definite
      conclusions. However, the results are in concordance with results from other
      studies.

PMID- 17018940
TI  - [Climateric symptoms and hormone replacement treatment among 50 years old
      Icelandic women.].
AB  - OBJECTIVE: The objective of the research was to estimate the prevalence and
      treatment of climacteric symptoms among 50 years old women, including which
      doctors are prescribing the hormone replacement treatment (HRT) and what
      information is given about the risk and benefit of HRT. MATERIAL AND METHODS: All
      (n=956) 50 years old women living in Reykjavik and neighbouring towns were
      included. A detailed questionnaire was posted to the women with two follow-up
      reminders. A non-response survey was conducted by phone among those not
      responding. RESULTS: The response rate was 72.2% (n=690). Sleep disturbances were
      the most common climacteric complaint occurring every day, mainly difficulty in
      maintaining sleep (14.8%). Hot flushes occuring every day (3.6%) and every night
      (2.2%) were more common than palpitations occuring every day (0.5%) and every
      night (0.2%). One fourth of the women had been to a doctor because of anxiety and
      17% because of depression. Women who had been oophorectomised, were suffering
      from insomnia, hypertension, had high body mass index (BMI) or were not on HRT
      were more likely to suffer from hot flushes and palpitations. More than every
      other woman was on HRT (54%). Combination of oestrogen and progesterone were most
      commonly used. Hot flushes were less common in women on HRT and one third
      reported better sleep after starting HRT. Women on HRT more frequently visited
      doctors, were more often suffering from anxiety, chronic tiredness, fibromyalgia
      and pain. They more often were heavy smokers and had chronic bronchitis. Most
      often the HRT was started by gynaecologists (67%) but continued by family doctors
      (56%). About one fifth claimed that they had not received information about the
      risk and benefit of HRT. CONCLUSIONS: More than every other 50 years old woman is
      on HRT. These women differ in various ways from women not receiving HRT, which
      underlines the importance of accurate diagnosis and treatment of climacteric
      symptoms. Better patient information is needed.

PMID- 17018941
TI  - [Height and weight of Icelandic children 6-20 years of age.].
AB  - INTRODUCTION: Monitoring growth rate in children reflects the state of health and
      nutrition of the individual as well as the state of health of a nation. Until now
      little information has been available about the growth pattern of Icelandic
      children. We report here the results of a nationwide cross-sectional study of
      growth in Icelandic children aged 6-20 years. MATERIAL AND METHODS: Height,
      standing and sitting and weight were measured in a total of 6500 schoolchildren,
      3173 girls and 3327 boys. The measurements were performed 1983-1987. Children
      were randomly selected from The National Registry according to date of birth from
      both urban and rural areas of the whole country of Iceland. Stature was measured
      by a Harpenden stadiometer and the children were weighed in underwear only using
      a standardized scale. RESULTS: The mean values and standard deviations for
      height, standing and sitting and weight are presented in tables. Growth charts
      for height weigt and sitting height are presented. No difference in height and
      weight was found between children from rural and urban areas. The results show
      that the growth of Icelandic children is in all age groups almost identical to
      the growth of Norwegian children. Compaired to other Nordic and WHO growth
      standards, Icelandic children are tall, especially during early pubertal
      development. CONCLUSIONS: Icelandic children are tall and the growth of Icelandic
      and Norwegian children follows the same pattern wich supports the theory that the
      two nations are closely related.

PMID- 17018942
TI  - [Kingella kingae ostemyelitis and septic arthritis in paediatric patients. Six
      cases from the Department of Pediatrics, National University Hospital of
      Iceland.].
AB  - Kingella kingae (K. kingae) is a gram negative rod most often associated with
      septic arthritis and osteomyelitis in children. Infections caused by K. kingae
      had not been reported in Iceland when six cases were diagnosed at the Pediatric
      Department at the National University Hospital of Iceland. In this report we
      describe those cases and review the literature.

PMID- 17018943
TI  - [Road traffic accidents, causes and causualities [Editorial].].

PMID- 17018944
TI  - [Organ Transplantation. An important element of the Icelandic Health Service
      [Editorial].].

PMID- 17018945
TI  - [Key issues concerning long-term management of transplant recipients.].
AB  - During the past 40 years, solid-organ transplantation has evolved into a routine
      clinical procedure for the management of end-stage heart, kidney, liver and lung
      disease as well as diabetes mellitus. This has mainly been accomplished through
      advances in understanding the molecular mechanisms involved in the rejection of
      allografts which has led to major improvements in immunosuppressive therapy. The
      discovery of the immunosuppressive drug cyclosporine which came into clinical use
      in the early eighties, revolutionized the field of transplantation. The short
      term survival of allografts is now excellent but relentless loss of grafts over
      time due to chronic rejection remains a major problem. A number of complications
      can affect transplant recipients, most of which result from intensive
      immunosuppressive treatment. Among those are life-threatening infections and
      malignancies. The key issues concerning long-term management of transplant
      recipients are discussed.

PMID- 17018946
TI  - [Access to transplantation organs in Iceland.].
AB  - After the first kidney transplantation into an Icelandic patient in 1970 and
      until 1993 Iceland was dependent upon the Nordic institution Scandiatransplant
      for transplantation of cadaveric kidneys. During that period 40 cadaveric kidneys
      were transplanted into Icelandic patients at Rigshospitalet in Copenhagen. The
      first liver was transplanted into an Icelander in London in 1985 and two in
      addition until 1993. The first heart was also transplanted into an Icelandic
      patient in London in 1988 and additional two until 1993. In 1991 the Icelandic
      parliament passed laws on the definition of death and procurement of organs for
      transplantation. This made it possible to provide organs to the Scandiatransplant
      collaboration. In 1993 a contract was made with the Sahlgrenska University
      Hospital in Gothenburg in which Sahlgrenska was committed to transplant
      necroorgans into Icelandic patients as well as to procurement of organs when
      available in Iceland. This cooperation lasted until the end of 1996 when a
      similar agreement was made with Rigshospitalet in Copenhagen. From 1993-1999
      altogether 28 necroorgan transplantations were performed on Icelanders (three
      hearts, three hearts and lungs, three lungs, seven livers and 12 kidneys). During
      the same period organs were procured 24 times. Transplantation of kidneys from
      living Icelandic donors has increased dramatically constituting 69% of all kidney
      transplantations 1990-1999. Living donor transplantations into Icelanders were
      altogether 56 at the end of 1999.

PMID- 17018947
TI  - [Renal transplantation.].
AB  - Renal transplantation is the treatment of choice for most patients with end-stage
      renal disease. The improved success of this treatment modality over the past four
      decades can large part be attributed to advances in immunosuppressive therapy.
      However, while the demand for renal transplantation has been steadily growing due
      to the rising incidence of end-stage renal disease, shortage of organ donors is a
      major limitation. The shortage of kidneys for transplantation has been met with
      an increase in the use of living donors. Renal allograft survival has improved
      over the years, although late graft loss is still a significant problem. One and
      five-year survival of living donor grafts is approximately 94% and 72%, and 88%
      and 60% for cadaveric donor grafts, respectively. The main causes of late graft
      loss are death of the patient and chronic allograft nephropathy. Risk factors for
      chronic allograft nephropathy are complex and include both immunlogic and non
      immunologic mechanisms. Finally, the results of renal transplantation in
      Icelandic recipients are discussed.

PMID- 17018948
TI  - [Liver transplantaion.].
AB  - In recent years, liver transplantation has become the treatment of choice for end
      stage liver disease. Chronic viral hepatitis, alcoholic cirrhosis and chronic
      cholestatic diseases are the most common liver diseases requiring
      transplantation. Complications of cirrhosis such as variceal bleeding are
      important indications. Prognostic survival models are also used to determine the
      optimal timing of transplantation. Pretransplant evaluation is designed to assess
      the patients general health and the condition of the vital organs. The operation
      is complicated but most patients recover rapidly. Postoperative complications
      such as hepatic artery thrombosis may require retransplantation. Following
      transplantation, the patient is maintained on a regimen of immunosuppressive
      medications. Acute cellular rejection is common but usually responds to
      additional immunosuppression. One and five years survival has increased to 80-90%
      and 65-70% respectively. Recurrent liver disease is a common problem but rarely
      affects short term survival. Several Icelandic patients have undergone liver
      transplantation. Indications are similar to other European countries.

PMID- 17018949
TI  - [Heart transplantation.].
AB  - Heart transplantation has been established as an accepted treatment for end-stage
      heart disease, in both adults and children. Survival following heart
      transplantation today is good, one year actuarial survival is 85% and
      approximately 65% after five years. Chronic rejection presenting as an post
      transplant coronary artery disease is the main limiting factor for long term
      survival. Complications from immunosuppression are troublesome, but quality of
      life is generally very good.

PMID- 17018950
TI  - [Lung transplantation.].
AB  - Lung transplantation is an option in the treatment of end stage lung diseases,
      excluding lung cancer, that lead to short life expectancy and poor quality of
      life. Now they are mostly limited by shortage of donor organs and longterm
      complications. They are used for various lung diseases such as pulmonary vascular
      diseases, fibrosing diseases, chronic obstructive pulmonary diseases and diseases
      that cause chronic infections. Depending on the indication it is possible to
      perform heart and lung transplantation, single lung or double lung
      transplantation.Indications, contraindications, surgical methods,
      immunosuppression, complications and outcomes will be discussed. Survival is not
      as good as for other solid organ transplantation. Measurement of pulmonary
      function and quality of life improve with lung transplantation. Bronchiolitis
      obliterans is the most common complication and is the most limiting factor. A few
      Icelanders have undergone lung transplantation, most of them in Gothenburg,
      Sweden. The future of lung transplantation depends on limiting the incidence of
      bronchiolitis obliterans and finding more organ donors.

PMID- 17018951
TI  - [Bone marrow transplantation.].
AB  - For the last few decades there has been a major increase in the number of
      allogeneic bone marrow transplantations and every year several thousand
      transplants are performed. In the early days of transplantation the treatment was
      performed only in terminally ill patients but now transplantation is carried out
      early in the course of the disease with greatly improved results. The most common
      indications for treatment today include acute and chronic leukemia, Non-Hodgkin s
      lymphoma, Hodgkin s disease, multiple myeloma and congenital immune deficiencies.
      Sibling donors are the most common source of stem cells for transplantation but
      in recent years international donor registries have played an increasing role.
      Degree of HLA disparity between donor and recipient is the main risk factor for
      Graft versus Host disease which is still the major cause of morbidity and
      mortality after transplantation. Graft rejection is very rare when there is
      complete HLA match between the donor and recipient. Overall survival is also
      dependent on several other factors including disease stage at time of
      transplantation, age and disease categories. For the last few years an average of
      four Icelandic patients have received bone marrow transplantation each year and
      indicatioons are similar to other European countries.

PMID- 17018952
TI  - [Illegal remedies in sports [Editorial].].

PMID- 17018953
TI  - [... when you are grown-up [Editorial].].

PMID- 17018954
TI  - [Puberty in Icelandic girls.].
AB  - In a crosssectional study, 2775 healthy Icelandic girls, aged 6-16 years, were
      examined for physical signs of puberty. The study was performed in 1983-1987 and
      was a part of a larger crosssectional study of growth and development of 5526
      Icelandic children all of whom were examined by the authors. Breast development
      stage 2 according to Tanner (B 2) was considered the first sign of puberty in
      girls. The mean age of Icelandic girls reaching B 2 was 10.84 years (SD 1.43).
      The mean time interval between B 2 and menarche was 2.42 years. The first signs
      of pubic hair growth, Tanner stage 2 (PH 2) were found at 11.46 years (SD 1.25).
      The mean time interval between PH 2 and PH 5 was 3.40 years. Comparison with
      studies from other countries is difficult because of different methods and
      different study designs, but the timing and tempo of puberty in Icelandic girls
      seems to be similar to what has been reported from other Nordic countries and
      countries in Western-Europe.

PMID- 17018955
TI  - [Puberty in Icelandic boys.].
AB  - In a crosssectional study, 2751 healthy Icelandic boys aged 6-16 years, were
      examined for physical signs of puberty. The study was performed in 1983-1987 and
      was a part of a larger crosssectional growth study of 5526 Icelandic children all
      of whom were examined by the authors. Testicular volume of 4 ml (T 4) was
      considered the first sign of puberty in boys. The mean age of Icelandic boys
      reaching T 4 was 11.89 years (SD 1.08). The mean time interval between T 4 and T
      12 was 2.21 years. The first signs of pubic hair growth, Tanner stage 2 (PH 2),
      were found at 12.74 years (SD 1.37). The mean time interval between PH 2 and PH 5
      was 2.43 years. Even though comparison with studies from other countries is
      difficult because of different methods and different study design, we find that
      the timing and tempo of puberty in Icelandic boys is similar to what has been
      reported from other Nordic countries and countries in Western-Europe.

PMID- 17018956
TI  - [Liver metastases of unknown origin.].
AB  - OBJECTIVE: Approximately 5% of cancer patients are diagnosed with tumour of
      unknown origin (3-4% in Iceland). Of those 10-30% have liver metastases. Liver
      metastases of unknown origin is thus not an uncommon problem. In the present
      study information about the origin and histology of liver metastases of unknown
      origin was compiled. MATERIAL AND METHODS: Records of all biopsies from liver
      metastases performed in the years 1987-1996 were retrieved from the medical
      database of the Department of Pathology at the University of Iceland. The
      biopsies came from a group of 176 patients. Ninety-two cases, in which the origin
      of the primary tumour was suspected or known, were excluded from the study,
      leaving 84 cases where the primary was completely unknown. The database of the
      Icelandic Cancer Society was used to gather data about the final tissue diagnosis
      and the location of the primary tumour when known. RESULTS: The Cancer Society
      data revealed the location of the primary tumour in 55 of the 84 cases of liver
      metastases of unknown origin. The most prevalent (75%) primary tumours were
      cancers of the pancreas (15), lung (13) and colon/rectum (12). The tissue
      diagnosis was adenocarcinoma in 33 of the 55 cases. In the male patients 83% of
      the adenocarcinoma metastases came from the colon/rectum or pancreas. The
      corresponding figure for the female patients was 67%, while 20% of the tumours in
      females originated in the gallbladder and biliary tree. CONCLUSIONS: In two
      thirds of the cases of liver metastases of unknown origin the primary tumour was
      later discovered. The most prevalent tumours were cancers in the pancreas, lung
      and colon/rectum. Adenocarcinoma was the tissue diagnosis in 60% of cases.

PMID- 17018957
TI  - [Advanced cardiac life support in the prehospital setting in the Reykjavik area
      1991-1996.].
AB  - Since 1982 an emergency ambulance manned by a physician and two emergency medical
      technicians has been operated in the Reykjavik area. The physicians have followed
      guidelines from the American Heart Association (AHA). Until 1986 the AHA
      guidelines had bicarbonate and in some instances calcium as first line treatment
      in cardiopulmonary resuscitation (CPR). OBJECTIVE: The purpose of this study was
      to evaluate the influence of the advanced cardiac life-support (ACLS) service and
      of bystanders on survival after cardiopulmonary arrest. Also to compare the
      survival rates to results of previous studies of CPR outside the hospital in the
      Reykjavik area. MATERIAL AND METHODS: The data was collected prospectively
      according to the "Utstein Style" form. From 1991-1996 there were 361 attempted
      resuscitations by the emergency crew. Fifty-three cardiac arrests were secondary
      to trauma, suicide, drowning, drug overdose and sudden infantile death. In 308
      cases of sudden cardiorespiratory arrest cardiac diseases were the presumed cause
      in accordance with the Utstein protocol. RESULTS: In the 308 cases the mean age
      was 67.2 years and the male/female ratio was 233:75. The mean response time was
      4.6 min. Patients admitted to the intensive or cardiac care units were 98 (31%)
      and 51 (17%) were discharged from the hospital. Ventricular fibrillation or
      ventricular tachycardia were the most common initial rhythms seen in 176 (57%)
      patients, asystole in 91 (30%) and other arrhythmias (EMD, agonal) in 41 (13%).
      Fourty-six patients (26%) with ventricular fibrillation on the first rhythm strip
      survived to be discharged from the hospital, three (3%) patients with asystole
      and two (5%) with other arrhythmias. Bystanders were present in 211 (68%) of
      cases and it fourfoulded the likelihood of discharge (OR 4.0; 95% CI 1.5-10.4;
      p=0.0025). There is no statistical difference in mean response time and survival
      rates between this study and previous studies from 1982-1986 and 1987-1990.
      CONCLUSIONS: When sudden cardiorespiratory arrest is witnessed the probability of
      survival is multiplied. We conclude that the results of ACLS outside the hospital
      in Reykjavik and surrounding area continue to be among the best. Changes in ACLS
      guidelines do not appear to have increased survival.

PMID- 17018958
TI  - [The impact of digital techniques on radiological services.].
AB  - All diagnostic imaging examinations may be performed digitally using computer
      techniques. The diagnostic reading in the imaging department can be made on a
      specialised computer screen and the images stored in a digital archive. The
      referring physician uses his computer to send requests and to read the reports.
      He can also access the images in the archive and view the images on a standard
      computer screen. The X-ray departments and their communication with referring
      physicians will be paper- and filmless, which results in considerable changes in
      working routines and increased speed of service. Digital X-ray techniques are
      described and some examples of digital services given.

PMID- 17018959
TI  - [Food-borne Infections in a new Millennium [Editorial].].

PMID- 17018960
TI  - [COX-II or NSAIDs - benefits? [Editorial].].

PMID- 17018961
TI  - [Thyrotoxicosis and coexistent diseases in atrial fibrillation.].
AB  - OBJECTIVE: To evaluate the prevalence of thyrotoxicosis and coexistent diseases
      in patients with atrial fibrillation admitted to a general medicine ward.
      MATERIAL AND METHODS: All patients with the discharge diagnosis of atrial
      fibrillation were studied. The study design was retrospective for the years 1993
      1994 and prospective from April 1995 through December 1997. Information on
      thyroid function tests was obtained from medical records in the retrospective
      part, but TSH, T4 and T3 were measured for patients admitted during the
      prospective part. Coexistent diseases were recorded. RESULTS: Atrial fibrillation
      was diagnosed in 167 patients (58 in the retrospective part and 109 in the
      prospective part). Males were predominant (59.3%) and the average age was 73.7
      years (span 26-100). Adequate information on thyroid function tests was available
      for 135 patients (58.6% of the retrospective part and 92.7% of the prospective
      part). 24 (17.8%) had abnormal thyroid function tests, predominantly women (71%).
      Ten had an isolated elevation of TSH, seven an isolated depression of TSH, two
      hypothyroidism and five other abnormalities. Hypertension was the most common
      coexistent disease (76 of 167 patients (45.5%). Ischemic heart disease was found
      in 44 (26.3%) and valvular heart disease in 27 (16.2%). No known coexistent
      disease was found in 32 (19.2%). CONCLUSIONS: 1) Thyrotoxicosis is rare in
      patients with atrial fibrillation who are admitted to a general medicine ward.
      Routine measurement of thyroid function tests in this patient population is
      therefore not warrented. 2) Unspecific abnormalities of thyroid function tests
      are common and are most likely due to diseases outside the thyroid gland or
      medications. 3) Hypertension, ischemic heart disease and heart valve disease are
      the most common coexistent diseases in this group of patients.

PMID- 17018962
TI  - [Thirty years of intensive care. Clinical experience at Reykjavik Hospital.].
AB  - OBJECTIVE: Reykjavik Hospital has been the main trauma center in Iceland. The
      Intensive Care Unit (ICU) was founded in 1970 and has been in operation since
      then. The aim of this study was to review its clinical experience these 30 years.
      MATERIAL AND METHODS: A retrospective study of patient records was conducted for
      all admissions to the ICU between 1970 and the end of 1999. Data was collected
      pertaining to the annual rate of admission, proportion of patients requiring
      ventilator treatment, mortality rate, age distribution, reasons for admission and
      medical speciality. RESULTS: A total of 13,154 patients were admitted to the ICU
      between 1970 and the end of 1999. A steady increase in the rate of admissions was
      observed during the study period, reaching 550-600 patients for the ICU annually.
      There was a statistically significant increase in the proportion of patients
      requiring ventilator treatment over the study period, reaching 38% of ICU
      admissions by the end of the study. During the study period only one
      statistically significant change was observed in age distribution. The annual
      rate of admission to the ICU for patients over 60 years of age increased
      significantly between the periods 1985-1989 and 1990-1999. The proportion of
      surgical patients increased (70% of patients by the end of the study) and the
      proportion of medical patients decreased (ending at 30% of patients). During the
      last decade a significant increase was seen in patients admitted after major
      surgery. The observed mortality rate in the final years of the study was observed
      to be significantly less than it had been in previous years. The observed
      mortality rate from 1970 to 1989 was 11.7% of patients, decreasing to 8.6% from
      1990 to 1998. The average length of stay was also observed to decline.
      CONCLUSIONS: The decline in mortality occurred in spite of an increased rate of
      admission and an increased workload. This change is attributed to improvement in
      the care of critically ill patients over the study period.

PMID- 17018963
TI  - [Aspirin. Acetylsalicylic acid and aspirinlike drugs. A review.].
AB  - In this review acetylsalicylic acid and aspirin with little "a" are considered as
      synonyms. A short acount is given of the history preceeding the synthesis of
      acetylsalicylic acid from salicylic acid by Felix Hoffmann in 1897 and its
      marketing in 1899 as Aspirin(R) by the Bayer Company. Aspirin was originally
      considered a prodrug to salicylic acid since it was at that time thought to have
      the same pharmacodynamic effects as salicylic acid and is rapidly transformed to
      it in vivo. Later aspirin was also found to be effective in its own right. During
      the years aspirin has gradually become the standard drug among an increasing
      number of aspirinlike drugs having similar effects as aspirin and often
      collectively, and somewhat misleading, named "nonsteroidal antiinflammatory
      drugs" (NSAIDs). The seminal work of John Vane and his colleagues in the 1970s
      and later has irrefutably tied the effects and side effects of aspirin and
      aspirinlike drugs to blocking of cyclooxigenase activity and therefore to reduced
      production of prostaglandins and related biogenic lipids. The anticoagulant
      effect, where aspirin itself is the cardinal drug, is thus due to decreased
      synthesis of thromboxan, whereas the antipyretic effect is due to reduced
      synthesis of prostaglandins in the central nervous system. The analgesic effect
      is obviously both related to decreased synthesis of prostaglandins in the central
      nervous system and outside it. On the other hand the antiinflammatory effect is
      seemingly mostly due to blocking inflammatory phenomena, without involvement of
      cyclooxigenase, in the walls of vessels although blocking the synthesis of
      prostaglandins also has a role. All aspirinlike drugs have until quite recently
      been mixed blockers of cyclooxigenases (COX 1 and COX 2) with aspirin itself
      being the most outstanding COX 1 blocker. New aspirinlike drugs with selective
      COX 2 blocking effect are apparently not any better on classical indications than
      the older drugs with mixed COX 1 and COX 2 blocking effect and their use might
      moreover be limited by some severe side effects. These drugs might, however,
      become of value for use on new indications.

PMID- 17018964
TI  - [Interest in breast cancer genetic testing among Icelandic women.].
AB  - OBJECTIVE: It is estimated that 6-10% of all breast cancers in Iceland can be
      attributed to inherited mutations in newly identified breast cancer
      susceptibility genes (BRCA1 and BRCA2). Before genetic testing becomes widely
      available in Iceland it is important to understand what motivates women s
      interest in undergoing testing as that will provide the data necessary for
      designing effective counseling interventions. Therefore, the aim of this
      population-based study was to examine interest in and predictors of interest in
      genetic testing among Icelandic women. MATERIAL AND METHODS: A randomly selected
      sample of 534 Icelandic women, who had not been previously diagnosed with breast
      cancer, completed questionnaires assessing, demographic/medical variables,
      interest in genetic testing, perceived risk of carrying mutations in BRCA1/2
      genes, cancer-specific distress and perceived benefits and barriers of genetic
      testing. The mean age was 53.8 years and 197 of the women had at least one first
      degree-relative that had been diagnosed with breast cancer. RESULTS: Interest in
      testing was high with 74% of the women indicating that they were interested in
      testing. Family history of breast cancer was unrelated to interest in testing
      whereas perceived risk of being a mutation carrier was significantly and
      positively related to interest in testing. Interest in testing was also
      significantly higher among younger women and among women with higher levels of
      cancer-specific distress. The most commonly cited reasons for wanting to be
      tested were to increase use of mammography screening and to learn if one s
      children were at risk for developing cancer. The most commonly citied reasons
      against being tested were fear of being mutation carrier and worry that test
      results would not stay confidential. CONCLUSIONS: These results suggest that
      demand for genetic testing, once it becomes commercially available, among
      Icelandic women may be high even among women without family history of breast
      cancer. The results also suggest that genetic counseling needs to address women s
      breast cancer worries as that may increase the probability that the decision to
      undergo testing is based on knowledge rather than driven by breast cancer fear
      and distress.

PMID- 17018965
TI  - [Birth control and pregnancy termination [Editorial].].

PMID- 17018966
TI  - [On allergy [Editorial].].

PMID- 17018967
TI  - [Hereditary hearing impairment. Mutation analysis of connexin 26 and POU3F4 genes
      in Icelanders with nonsyndromic hearing impairment.].
AB  - AIMS: Mutations in the connexin 26 (Cx26) gene have recently been shown to be a
      major cause of hereditary nonsyndromic sensorineural hearing impairment in
      Caucasians. Studies indicate that approximately 10-30% of all childhood deafness
      are due to Cx26 mutations and the most frequently observed mutation is Cx26
      35delG. Mutations in the POU3F4 are the most common cause of X-linked
      nonsyndromic hereditary hearing impairment. The aim of our study was to determine
      presence and type of Cx26 and POU3F4 mutations in an Icelandic cohort with
      nonsyndromic hearing impairment. MATERIAL AND METHODS: All 15 individuals
      participating in the study, fulfilled the criteria of severe congenital
      nonsyndromic hearing impairment of unknown cause and the hearing loss was
      documented by audiologic testing in a clinical facility. Eleven had a family
      history and four were sporadic cases. All exons of the Cx26 and POU3F4 genes were
      amplified using PCR and six pairs of primers. The amplified DNA fragments were
      screened for sequence variations using enzymatic mutation detection and the
      nucleotide sequence of fragments showing signs of variation was determined.
      RESULTS AND CONCLUSIONS: Using the methods described above four distinct sequence
      variations were detected in the Cx26 gene. The 35delG allele causing hereditary
      recessive hearing impairment was identified in one homozygous and one
      heterozygous individual. The heterozygous 35delG individual was also shown to
      carry the recessive allele 358-360delGAG (E). A missense mutation, 101Teth C
      (M34T), supposed to cause autosomal dominant form of hearing impairment with
      variable penetrance, was detected in one heterozygous individual. A novel
      sequence variation without known clinical significance, -63Teth G, was found in
      the 5'-noncoding sequence in one control sample. No mutations were detected in
      the POU3F4 gene.

PMID- 17018968
TI  - [Atrial fibrillation: therapeutic options at the turn of the century.].
AB  - Atrial fibrillation is an increasing health care problem and the incidence of
      this arrhythmia is expected to increase substantially in the next two decades.
      Atrial fibrillation can be seen in patients with structural heart disease as well
      as those who have a normal heart. A variety of underlying mechanisms can lead to
      atrial fibrillation, including parasympathetic stimulation causing vagal atrial
      fibrillation. Complications of atrial fibrillation include congestive heart
      failure and stroke. Atrial fibrillation is an independent risk factor for
      increased mortality. In recent years a number of new treatment options have
      emerged. Anticoagulation decreases the risk of stroke and new antiarrhythmic
      drugs have been developed which increase the likelihood of conversion to and
      subsequent maintenance of sinus rhythm. In addition there have been advances in
      the approach to electrical cardioversion. Radiofrequency ablation therapy is a
      promising option in the treatment of atrial fibrillation and could be
      increasingly utilized in the near future. This paper focuses on advances in the
      therapy of atrial fibrillation, including new pharmacological agents,
      radiofrequency ablation and electrical cardioversion.

PMID- 17018969
TI  - [Allergy and intolerance to food in an Icelandic urban population 20-44 years of
      age.].
AB  - OBJECTIVE: Symptoms related to the intake of certain food items are common. In
      most of these cases food allergy/intolerance can not be confirmed. In the
      Icelandic part of the European Community Respiratory Health Survey the prevalence
      of food-related symptoms was assessed among adult Icelanders. MATERIAL AND
      METHODS: Three thousand and six hundred men and women, 20-44 years, were studied,
      among them 800 were randomly chosen for a more detailed investigation.
      Additionally, all those using asthma medication or having asthma symptoms were
      investigated. A questionnaire inquired about chest symptoms, symptoms related to
      food-intake and eating habits. In Iceland additional questions were asked
      concerning drug intolerance, urticaria, Quincke oedema, childhood eczema,
      migraine and psoriasis. All subjects underwent skin prick tests against 12 common
      allergens, spirometry and methacholine challenge. Specific IgE antibodies against
      five airborne allergens and six common food allergens were measured. RESULTS:
      Among subjects with food-related symptoms, 68% reported complaints from the GI
      tract, 22% had skin rash or pruritus, 15% severe headache, 11% breathlessness, 8%
      a running/stuffy nose and 4% fatique. Altogether 42 food items were considered
      likely causes of the reported symptoms. Twenty-two percent of the random sample
      had symptoms related to the intake of a particular food and 15% reported always
      having the same symptom after intake of this food. Women reported food-related
      symptoms somewhat more often that men (17% and 13% respectively (p=0.21)). In the
      random sample only 1.8% had antibodies to one or more of the foods measured.
      There was a significant relationship between food-related symptoms and reported
      migraine, urticaria and Quincke oedema and a particularily strong relationship
      with drug intolerance. Migraine, urticaria, Quincke oedema and drug intolerance
      were significantly more common among women (p<0.0001, p<0.01, p<0.05 and <0.002
      respectively). No relationship was seen between food-related symptoms and
      positive methacholine tests. CONCLUSIONS: In conclusion this study reveales a
      large group of subjects reporting food-releated symptoms. This group also
      reported a big prevalence of unrelated symptoms such as drug intolerance and
      migraine. Type-1 allergy is unlikely to be the cause to more than a small part of
      these symptoms.

PMID- 17018970
TI  - [The prevalence of sicca symptoms in Iceland.].
AB  - OBJECTIVES: Sjoegren' syndrome is one of the most common inflammatory systemic
      rheumatic disorders. The syndrome is characterised by tiredness, pain problems
      and mucosal dryness. The goal of this study is to elucidate the prevalence of
      sicca symptoms in the Icelandic population and to calculate the preliminary
      prevalence value for Sjoegren' syndrome in Iceland. MATERIAL AND METHODS: Random
      sample was retrieved from two age groups; 40-49 and 70-75 years Icelandic
      inhabitants of Reykjavik and Akureyri. Questionnaire with 14 questions of the
      most common symptoms of Sjoegren' syndrome was mailed to those sampled. A small
      sample was evaluated by Schirmer-I test, tear film break up time (BUT) and Rose
      Bengal score for keratoconjunctivitis sicca (KCS) and unstimulated salivary flow
      rate was performed. RESULTS: The questionnaire was sent to 621 subjects, 300 male
      and 321 female. The response rate was 74%. Of those 20.3% had subjective symptoms
      of dry eyes and 12.0% of dry mouth according to the six questions used in the
      European classification criteria (EEC). The prevalence of both was higher in
      females (p<0.05). Of the 23 subjects who reported sicca symptoms, fatigue and
      pain problems; 26% had abnormal Shirmer-I test, 13% had abnormal BUT and 39% had
      abnormal salivary flow rate, two of those individuals fulfilled the EEC criteria
      for Sjoegren' syndrome (0.2%; 0-0.5%, 95% CI). None in the age and sex matched
      control group fulfilled the EEC criteria. CONCLUSION: The subjective symptoms of
      dry eye and dry mouth are common in Iceland, as are the three major symptoms of
      Sjoegren' syndrome. Standardised objective diagnostic criteria is necessary when
      the diagnosis of the syndrome is made.

PMID- 17018971
TI  - [CPR-911].

PMID- 17018972
TI  - [Prehospital cardiac life support in the Reykjavik area 1999-2002].
AB  - OBJECTIVES: A physician manned ambulance has provided advanced resuscitation
      service in the Reykjavik area for over 20 years. Out of hospital resuscitation
      since 1982 has been done with average response time of 4.6-4.9 minutes, the
      survival rate to hospital admission has been 31-40% and survival to hospital
      discharge 16-17%. In the years preceding this study, several changes were done in
      the service; the service area was enlarged, dispatch was centralized to one
      emergency number, the training of EMT s and physicians was improved and a two
      tier rendezvous system was adopted. Cell phone coverage reached over 90% of the
      population. The study was done in 1999-2002 with the objective to: 1. measure the
      results of attempted prehospital resuscitations for cardiac diseases in the area,
      2. to monitor the effect of bystander response, 3. to estimate the effect of
      changes in the service prior to the study period. MATERIALS AND METHODS: A
      ambulance staffed with EMTs and one with a physician were dispatched to all
      possible cases of cardiac arrest. Resuscitation was attempted using the AHA
      guidelines for resuscitation. Prospective data was collected following the
      Utstein template recorded by the physician on call. RESULTS: A total of 319
      resuscitative attempts were made during the years 1999-2002, excluding hanging,
      SIDS, drowning, suicide, trauma, internal bleeding and other diseases, a total of
      232 arrests were considered of cardiac origin giving an incidence of
      33/100,000/year. The average response time was 6,1 min. Of 232 cardiac
      resuscitation attempts 140 patients (60%) were in VF/VT, 53 (23%) in asystole and
      39 (17%) in other rhythms. Ninety-six (41%) of all patients survived being
      admitted to hospital ward and 44 (19%) survived to discharge with 39 being alive
      at 12 months. Of patients in VF/VT, 79 (56%) survived to hospital admission and
      39 (28%) to hospital discharge. Resuscitation was more successful in cases of
      witnessed arrest and if CPR was attempted by bystanders. CONCLUSION: Despite
      various changes in the EMS system, the results of resuscitative attempts are
      similar to previous studies in the area but an increased proportion of survivors
      is left with neurological damage. In 54% of the cases COR was performed by
      bystanders. Response time needs to be shortened and CPR training increased.

PMID- 17018973
TI  - [Health promotion in pre-schools in Reykjavik--risk assessment in the year 2000].
AB  - OBJECTIVE: The purpose of this research is to assess the work environment and
      compare with the well-being of employees of pre-schools. MATERIAL AND METHODS:
      Work environment of 16 pre-schools was assessed by a specialist in ergonomics and
      a questionnaire on work environment and health. Based on the ergonomic assessment
      the schools were classified into four groups. This was then compared to the
      results from the questionnaire. RESULTS: About 90% of the employees (n=320)
      returned the questionnaire and the ergonomic workplace assessment was done before
      the results from the questionnaire were processed. Substantial job-satisfaction
      characterizes the work done in the pre-schools, more so in the smaller schools,
      where the physical work environment is worse, but the employees are older and
      more likely to have professional background for the job. In contrast job
      satisfaction was less where the objective physical work environment was better.
      Strain symptoms were least apparent among the younger employees, who had the best
      work environment. About half of the employees had received instructions about
      work positions and reported that such was useful. Noise was over limits in most
      of the assessments and the employees reported in 80% of such incidents had the
      noise caused discomfort in the past month. Work positions close to the floor were
      quite common regardless of other circumstances among the employees. CONCLUSION:
      Work environment in pre-schools is characterized by substantial physical and
      mental strain. Despite of that it is also characterized by substantial work
      satisfaction, indicating that work satisfaction is not a sign per se of good work
      environment.

PMID- 17018975
TI  - [Prenatal diagnosis - for whom? [Editorial].].

PMID- 17018976
TI  - [The development of prenatal diagnosis [Editorial].].

PMID- 17018977
TI  - [Ultrasound screening at 18-20 weeks.].
AB  - Ultrasound screening at 18-20 weeks gestation is widely recognized as an integral
      part of modern antenatal care. It was set up in Iceland between 1984 and 1986 and
      has become steadily more advanced. The time for this basic dating and fetal
      assessment scan was selected in accordance with current medical knowledge, based
      on several cohort studies, later supplemented by results from randomized trials.
      Icelandic reference standards were established and the suitability of mostly
      Scandinavian fetal assessment methods for the Icelandic population was evaluated.
      Gestational age assessment and placental localisation, along with a thoroughly
      performed evaluation to ascertain normal fetal anatomy, were conducted
      systematically. Icelandic guidelines and educational standards for conducting
      ultrasound were published. As most deviations from the normal, including major
      anomalies, are found in those not perceived to be at risk, a screening approach
      was necessary. Better dating of pregnancies and prenatal diagnosis allowing
      either termination of pregnancy in case of severe fetal anomaly or preparation
      for correct handling of the neonate at birth, have had a major impact on
      obstetric practice. Most lethal or seriously handicapped fetuses are detected.
      The screening scan has become a universally accepted and appreciated part of
      antenatal care in Iceland.

PMID- 17018974
TI  - [The frequency of some factors in pregnancy and delivery for Icelandic children
      with ADHD].
AB  - OBJECTIVE: ADHD is a well known psychiatric disorder that begins in childhood and
      frequently persists into adulthood. In the last decade numerous studies have
      shown the importance of genetic factors in the etiology of ADHD. However other
      etiological factors seem to be involved. The aim of this study was to examine the
      frequency of some possible etiological factors for ADHD in Icelandic children
      diagnosed with ADHD. The study is descriptive. MATERIALS AND METHODS: The
      participants were 196 children referred for suspected ADHD to the outpatient unit
      of the Department of Child and Adolescent Psychiatry, Landspitali University
      Hospital during a 2 year period 1998-1999. The participants had either ICD-10 or
      DSM-IV hyperkinetic disorder and/or ADHD and the information was obtained from
      patient case notes. Information provided by parents in a questionnaire concerning
      health in pregnancy and the perinatal period was retrospectively analysed.
      RESULTS: The main results show statistically significant increased risk for ADHD
      associated with several factors such as low birthweight, young age of the mother
      at the time of the child's birth and Caesarean section, compared with reference
      groups such as mean values in all of the community. Other factors such as
      birthweight, alcohol or tobacco use in pregnancy, use of medication in pregnancy
      or vacuum extraction did not show statistically significant association with
      ADHD. CONCLUSION: The results indicate as some studies from other countries have
      suggested that an association exists between a number of factors in pregnancy,
      delivery and perinatal period and ADHD, even though there is still not enough
      evidence to confirm definite etiological factors.

PMID- 17018978
TI  - [Prenatal diagnosis of heart disease.].
AB  - Fetal echocardiography is a detailed examination of the fetal heart, its anatomy
      and function, performed with high frequency, high-resolution ultrasound probes.
      Advancements in echocardiographic technology have made possible accurate
      diagnosis of complex cardiac defects from a transabdominal approach, as early as
      14-18 weeks of gestation, although optimal images are usually acquired at 20
      weeks of gestation. Indications for fetal echocardiogram are maternal or fetal
      factors that place the fetus at increased risk for having heart defect but
      suspected cardiac abnormality on a level 1 scan is the most frequent referral
      indication and the one indication with the highest yield of positive fetal
      echocardiogram. Diagnosis of fetal heart disease can have major influences on the
      prenatnal and postnatal management and enables parents to prepare and plan for
      the birth of a child with a cardiac defect.

PMID- 17018979
TI  - [Fetal nuchal translucency measurement at 11-13 weeks and risk assessment for
      fetal aneuploidy and cardiac anomalies.].
AB  - Ultrasound is currently an integral part of prenatal care. In Iceland, all women
      are offered one ultrasound examination at 18-20 weeks, to assess fetal health,
      number of fetuses, placental location and to calculate the estimated due date.
      Also, about one third will have an early ultrasound examination due to pain,
      bleeding or uncertain dates. All women, aged 35 and older, are offered an
      amniocentesis for fetal karyotyping, due to the increased rate of chromosomal
      abnormalities with advancing maternal age. Younger women are not routinely
      offered fetal karyotyping. In this review, a method is described that can
      estimate the risk of chromosomal abnormalities based on an ultrasound examination
      at 11-13 weeks. The fetal crown rump length and nuchal translucency are measured
      in a sagittal view. Based on these measurements as well as maternal age, risk
      assessment for fetal aneuploidy is performed. A screen positive rate of 8% is
      expected if risk assessment for fetal aneuploidy is 1:300 or higher. This
      translates into 8% procedure rate for fetal karyotyping. This approach leads to
      the diagnosis of the majority of all fetal trisomies. The method was developed by
      the Fetal Medicine Foundation, London, and is now widely used throughout Europe
      and Canada. The institution teaches the methodology and offers continuous audit
      for quality assurance. If this methodology were to be applied in Iceland the
      procedure rate for fetal karyotyping could be reduced from 13% to 8% while
      improving diagnosis of trisomy 21 from 30% to 80%. The option of offering all
      expecting couples an early ultrasound and risk assessment for fetal trisomies
      should be considered.

PMID- 17018980
TI  - [Risk assessment for fetal aneuploidy after nuchal translucency measurement.].
AB  - In this article the focus is on the estimation of a likelihood ratio by using
      software which calculates the risk for trisomy 13, 18 and 21. It is based on the
      woman s age, crown rump length of the fetus and its nuchal translucency
      measurement. Examples are given based on different maternal age, previous history
      and results of ultrasound examination.

PMID- 17018981
TI  - [Biochemical screening for fetal abnormalities - alpha-fetoprotein.].
AB  - The use of maternal serum alpha-fetoprotein (MSAFP) in screening for open neural
      tube defects and other fetal abnormalities is discussed. The arguments for the
      introduction of this screening test in certain areas of Iceland are provided and
      its possible application. MSAFP could be used as part of the triple test used for
      the screening of chromosomal abnormalities at 15-18 weeks of pregnancy, or as a
      single marker for neural tube defects.

PMID- 17018982
TI  - [Biochemical antenatal screening for fetal anomalies.].
AB  - Biochemical antenatal screening started 30 years ago. Initially, the goal was to
      detect neural tube defects by measuring a-fetoprotein in maternal serum (MS-AFP)
      and amniotic fluid (AF-AFP). The serendipitous discovery of an association
      between low AFP maternal serum concentration and chromosomal anomalies resulted
      in increased research interest in biochemical screening in pregnancy.
      Subsequently double, triple or quadruple tests in 2nd trimester of pregnancy
      became widely used in combination with fetal chromosome determination in at risk
      individuals. In Iceland, antenatal screening for chromosomal anomalies has
      essentially been based on fetal chromosome studies offered to pregnant women 35
      years or older. This strategy needs to be revised. Recently first trimester
      biochemical screening based on maternal serum pregnancy associated plasma protein
      A (MS-PAPP-A) and free b-human chorionic gonadotropin (MS-free b-hCG) and
      multivariate risk assessment has been developed. This screening test can be
      improved if done in conjunction with nuchal translucency measurements in an early
      sonography scan.

PMID- 17018983
TI  - [Risk assessment for fetal trisomy 21 based on nuchal translucency measurement
      and biochemical screening at 11-13 weeks.].
AB  - Screening for fetal aneuploidy during the first trimester using fetal nuchal
      translucency measurement and maternal serum free ss-hCG (ss-human chorionic
      gonadotropin) and PAPP-A (pregnancy associated plasma protein A) is commonly
      practised. An approach with a one stop clinic for assessment of risk for fetal
      anomalies, where pre-test counseling, blood test, ultrasound and post-test
      counseling is offered in one hour visit is described. Based on maternal age,
      biochemistry and fetal nuchal translucency measurement an estimated risk for
      fetal trisomies 13,18 and 21 is calculated. The main benefit of this approach in
      screening for fetal aneuploidy is the short turnaround time, with immediate
      results and a low screen positive rate. This approach leads to diagnosis of the
      majority (95%) of fetal aneuploidy cases. If screening is positive a diagnostic
      test is available with chorionic villous sampling or amniocentesis. In Iceland,
      fetal karyotyping is offered to women 35 years and older and performed during the
      second trimester, but by using this approach prenatal diagnosis can be moved to
      the first trimester and also offered to women of all ages. A screening approach
      with a series of steps from 10-15 weeks, including maternal blood test at 10 and
      again at 15 weeks, as well as an ultrasound and nuchal translucency measurement
      at 11-13 weeks, with integrated results at 15+ weeks has been proposed. This
      method offers even lower screen positive rate (1%) while detection rates of fetal
      aneuploides are high (>90%) but it requires four visits instead of one and the
      prolonged approach is likely to cause excess anxiety for the parents to be. If
      all women are to be offered prenatal sreening in the first trimester the
      structure of prenatal care in Iceland needs some modifications including
      scheduling the first prenatal visit at 8-10 weeks and teaching healthcare
      providers counseling regarding prenatal testing.

PMID- 17018984
TI  - [Amniocenteses and chorion villus biopsies to diagnose fetal karyotyping.].
AB  - In this article amniocenteses and chorion villus biopsies are reviewed. The
      technique is described for both procedures and any side effects discussed, both
      immediate and possible long term effects. The procedures are compared in terms of
      timing during pregnancy, complication rates and accuracy of test results.

PMID- 17018985
TI  - [Chromosomal analysis as a means of fetal diagnosis.].

PMID- 17018986
TI  - [Fetal nuchal translucency measurements in women aged 35 and older. Results from
      1.1. 99-31.12.00.].
AB  - OBJECTIVE: Based on a combination of ultrasound fetal nuchal translucency
      measurement at 11-13 weeks and maternal age, a risk assessment for fetal
      aneuploidy is calculated. This method identifies a subgroup at risk for fetal
      aneuploidy, with less invasive testing while increasing the number of fetal
      aneuploidy cases diagnosed, compared to the current approach in Iceland where
      fetal aneuploidy risk is based on maternal age only. MATERIAL AND METHODS: All
      women who presented for an ultrasound and counselling in preparation for an
      amniocentesis, the majority for advanced maternal age, were offered nuchal
      translucency measurement and risk assessment for fetal aneuploidy. RESULTS: In
      1999 a total of 477 nuchal translucency measurements were performed. Ten fetuses
      (2.1%) had risk assessment for fetal aneuploidy above 1:300 leading to diagnosis
      of 5/6 (83%) trisomy 21 cases and two other fetal aneuploidy cases within the
      group. Three fetuses who had increased nuchal translucency and normal karyotype
      were normal at birth. Three women who underwent an amniocentesis in spite of risk
      assessment less then 1:300 had aneuploid fetuses. Ultrasound and nuchal
      translucency measurement lead to the diagnosis of 7/10 fetal aneuploidy cases
      within the group. In 2000 a total of 418 nuchal tranlucency measurements were
      performed. Nine fetuses (2.15%) had risk assessment for fetal aneuploidy above
      1:300 leading to diagnosis of 1/1 trisomy 21 case and 2/2 other fetal aneuploidy
      cases within the group. One fetus had multiple anomalies and the pregnancy was
      terminated without prior karyotyping. Of the five fetuses who had a normal
      karyotype one had cardiac abnormality and one an omphalocele. The remaining three
      were healthy at birth. Ultrasound and fetal nuchal translucency measurements lead
      to the diagnosis of all fetal aneuploidy cases within the group. CONCLUSIONS:
      During 1999 and 2000 ultrasound and fetal nuchal translucency measurements in a
      selected subgroup at risk for fetal aneuploidy lead to the diagnosis of 7/10 and
      3/3 fetal aneuploidy cases with 2.1% positive screen rate.

PMID- 17018987
TI  - [Counselling regarding ultrasound excaminations in pregnancy.].
AB  - In this article the focus is on how midwifes, nurses, doctors and other staff who
      work in prenatal care give counselling regarding ultrasound excaminations in
      pregnancy. The main goal is to give professional information regarding the
      examinations which are available so that parents truly have an informed choice.
      All decisions regarding the pregnancy must always be with the parents.

PMID- 17018988
TI  - [Prenatal diagnosis. Ethics - counselling.].
AB  - During the last years great progress has been made in the field of prenatal
      diagnosis. The possibility of monitoring the growth, development and well being
      of a child in the womb is priceless and can offer the mother a sense of security
      regarding the pregnancy. But the growing technology leads at the same time to
      various questions and discussions and it is good for all those who are a part of
      the maternal care to think about them. Is it unquestionable to eliminate all
      those fetuses that are diagnosed with an abnormality of any kind? Where would
      such a development lead us? Are we, with the means of a continuing better
      technology, bit by bit "eliminating" certain groups within the society? Is it to
      be an unquestioned "routine" or even duty, that every woman should be subjected
      to those diagnoses that are possible? We have within the field of ethics many
      different views on those questions. One view stresses the complete freedom of
      abortion. Another demands that all life should be protected, and a fetus should
      never be terminated, even if it is sick or disabled. The author of this article
      wants to demonstrate the rule of the sanctity of all life, that all human life
      should be respected, that this rule should always be applied within the field of
      medicine. At the same time it should be stressed that this respect for life is
      not always best given by sustaining and saving all life. Death is not always the
      worst choise. We must evaluate each and every case, that each and every parents
      to be should make their own decision based on their own ethical views, after
      having received appropriate information, professional support and counselling. It
      is important that professionals deal with these matters with respect for life and
      respect for the parents who already have disabled children and the disabled
      themselves. All the prenatal diagnosis which is available may lead to that
      parents to be have to take difficult decisions regarding the pregnancy. It is
      therefore of the utmost importance that a pregnant woman and her partner should
      know the meaning and purpose of the prenatal care which is offered and that they
      are fully aware of the decisions they may have to face. If the results are not in
      the favor of the fetus, the couple should receive the support and care whatever
      their decision may be.

PMID- 17018989
TI  - [Clinical diagnosis - Art and science in continious evolution [Editorial].].

PMID- 17018990
TI  - [The development of prenatal diagnosis [Editorial].].

PMID- 17018991
TI  - [Familial hypercholesterolemia in Iceland. Review and outcome of family
      screening.].
AB  - Familial hypercholesterolemia is a genetic disorder causing lifelong elevation of
      cholesterol and severely increased risk of coronary heart disease. Cholesterol
      lowering drug treatment is usually effective and clinical trials indicate a
      substantial lowering of risk, thanks to treatment. The diagnosis is based on
      cholesterol level in the individual and in his/her closest relatives or on a
      genetic test. The prevalence is estimated 1/500. In Iceland nearly half of the
      estimated number of individuals with familial hypercholesterolemia has been
      diagnosed (about 200). Three mutations have been identified that cause familial
      hypercholesterolemia in the Icelandic population and the most common one is
      estimated to cause 60% of the disease in Iceland. In this paper we give a short
      review of the literature on familial hypercholesterolemia especially regarding
      risk of coronary heart disease and describe the results of screening for the
      disease in Iceland. Also we present a new campaign to find undiagnosed
      individuals with the disease.

PMID- 17018992
TI  - [Home mechanical ventilation in Iceland.].
AB  - OBJECTIVE: To describe the users of home mechanical ventilation treatment in
      Iceland. MATERIAL AND METHODS: Records for all patients in Iceland using
      noninvasive ventilatory support at home on April 30th 1999 were analysed.
      RESULTS: A total of 54 patients were using ventilatory support at home. There
      were 33 males and 21 females. The mean age for the group was 61 years. The mean
      treatment time was 3.5 years. The majority were using pressure controlled
      ventilators that were connected to a nose mask or full face mask. The most common
      reason for treatment was decreased respiratory muscle function. In 11 patients
      this was secondary to muscle- or neurological diseases, in nine from TBC sequelae
      and in six post polio or from idiopathic kyphoscoliosis. In addition there were
      21 patients that had a combination of chronic obstructive pulmonary disease and
      sleep-related breathing disorder. Cheyne-Stoke breathing secondary to congestive
      heart failure was the reason for home ventilatory treatment in five males and two
      females. These patients had relatively normal spirometric and bloodgas results,
      which is in contrast to the rest of the group, where spirometric values were on
      the average less than 50% of predicted. Arterial blood gases commonly showed
      hypoxia and 16 of the patients had long-term oxygen therapy (over 16 hrs/day).
      CONCLUSIONS: Home ventilatory treatment has become part of medical treatment in
      Iceland and benefits patients with decreased ventilatory function, especially
      during sleep.

PMID- 17018993
TI  - [Hepatocellular carcinoma in Iceland.].
AB  - INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) varies throughout
      the world, being relatively low in Northern Europe (less than five per 100,000
      population) where the majority of the patients have cirrhosis. In Iceland the
      prevalence of viral hepatitis and cirrhosis, the main risk factors for HCC, is
      lower than reported in many other countries. The aim of our study was to
      investigate the incidence and etiology of HCC in Iceland. MATERIAL AND METHODS:
      All patients diagnosed with HCC in Iceland in 1984-1998 were included in the
      study. Histologic diagnosis was required for inclusion. Patients were identified
      from the Icelandic Cancer Registry and by reviewing autopsy and histopathology
      reports. Further information was obtained from medical records. RESULTS: A total
      of 71 cases of HCC were identified, 51 males and 20 females. The mean age for
      males was 69.3 years (18-95) and 73 years (52-89) for females. The age
      standardized annual incidence rate of HCC was 1.08/100,000 (males 2.10, females
      0.67). The incidence did not increase significantly during the study period.
      Alcohol abuse (15.5%) and hemochromatosis (11%) were the most common risk
      factors. Twenty-three (32%) had cirrhosis but 39 (55%) had no known risk factors.
      Of 55 cases where non-neoplastic tissue was available for examination, 27 had
      liver disease. CONCLUSIONS: 1) The incidence of HCC in Iceland is lower than
      reported in other countries. 2) Alcohol abuse and hemochromatosis are the most
      common risk factors. 3) The ratio of patients with cirrhosis is low.

PMID- 17018994
TI  - [The importance of summer holidays [Editorial].].

PMID- 17018995
TI  - [Is laparoscopic appendectomy better than open conventional appendectomy?
      [Editorial].].

PMID- 17018996
TI  - [Colorectal liver metastasis. An evidence based review on surgical treatment.].
AB  - Liver metastases are common in patients with colorectal cancer, liver resection
      being the only well documented curative treatment. In this evidence based review,
      improved results after liver resection are presented and stated how patients are
      best selected for surgery using specific selection criteria.

PMID- 17018997
TI  - [Cure after re-resection of colorectal liver metastases in a 28 year old woman. A
      case report.].
AB  - Liver resection is the only well documented curative treatment for colorectal
      liver metastases but without surgery survival is dismal. Liver resections can be
      done for re-metastatic colorectal cancers if the tumors are localized in the
      liver. The first case of re-resection of colorectal liver metastases in Iceland
      is presented.

PMID- 17018998
TI  - [Atopy and allergic disorders among Icelandic medical students.].
AB  - OBJECTIVE: To compare the prevalence of IgE-mediated sensitization, allergic
      disorders and possible risk factors for atopic sensitization among Icelandic
      medical students (n=113) to a randomly chosen age matched group previously
      investigated in the Icelandic part of the European Community Respiratory Health
      Survey. MATERIAL AND METHODS: Altogether 100 medical students participated and
      102 in the control group. They were skin prick tested and they answered questions
      about respiratory symptoms, smoking habits, family history and home environment
      in childhood. RESULTS: Only 4% of medical students reported daily smoking
      compared to 27% of the controls. The medical students also had a significantly
      lower number (mean +/- SD) of siblings (2.2+/-1.3) compared to the controls
      (3.9+/-1.7). The controls also shared bedrooms with older siblings in childhood
      three times as often. Atopic sensitization, defined as a positive (3 mm or more)
      reaction to at least one of nine common airborne allergens used in testing, was
      found in 41% of the medical students compared to 26.5% of the controls. The
      prevalence of asthma and urticaria was also significantly higher among the
      medical students. CONCLUSIONS: Medical students have more often IgE-mediated
      sensitization and allergy related diseases than a controlgroup of the same age. A
      possible explanation to this is a lower number of siblings among medical students
      and a different household situation in childhood.

PMID- 17018999
TI  - [Mesenchymal stem cells. A review.].
AB  - The bone marrow contains various types of stem cells. Among them are
      hematopoietic stem cells, which are the precursors of all blood cells, and
      mesenchymal stem cells. Mesenchymal stem cells have recently received a lot of
      attention in biological research because of their capability to self renewal, to
      expand and transdifferentiate into many different cell types; bone cells,
      adipocytes, chondrocytes, tendocytes, neural cells and stromal cells of the bone
      marrow. Mesenchymal stem cells can be cultured in vitro although their
      differentiation potential is not yet fully understood. Several experiments have
      been conducted in animal models where mesenchymal stem cells have been
      transplanted in order to enhance hematopoiesis or to facilitate the repair of
      mesenchymal tissue. Similar experiments are being conducted in humans.
      Mesenchymal stem cells are believed to be able to enhance hematopoietic stem
      cells transplantation by rebuilding the bone marrow microenvironment which is
      damaged after radiation- and/or chemotherapy. Mesenchymal stem cells are
      promising as vehicles for gene transfer and therapy. It may prove possible to
      tranduce them with a gene coding for a defective protein i.e. collagen I in
      osteogenesis imperfecta. The cells could then be expanded ex vivo and
      transplanted to the patients where they home to the bone marrow, differentiate
      and produce the intact protein. Future medicine will probably involve mesenchymal
      stem cells in various treatment settings.

PMID- 17019000
TI  - [Risk behaviour at annual youth festivals [Editorial].].

PMID- 17019001
TI  - [The role of inhaled corticosteroids in the treatment of chronic obstructive
      pulmonary disease is getting clearer [Editorial].].

PMID- 17019002
TI  - [Trends in overweight and obesity in 45-64 year old men and women in Reykjavik
      1975-1994.].
AB  - OBJECTIVE: The aim of this study was to assess possible changes in the prevalence
      of overweight and obesity in Iceland during the last decades. Furthermore, the
      possible effect of dietary changes on the observed trend in obesity prevalence
      was evaluated. MATERIAL AND METHODS: Participants came from stages III-V in the
      Reykjavik Health Study and the Reykjavik part of the MONICA studies from the
      period 1975-1994. The age groups 45-54 years and 55-64 years were examined. Only
      the information from the first visit of each person was included. The body mass
      index (BMI) for the participants was calculated and the percentage of those
      subjects considered overweight and obese according to WHO standards evaluated,
      using 25BMI<30 kg/m(2) as the cut-off point for overweight and BMI30 kg/m(2) as
      the cut-off point for obesity. Also, the observed trend in obesity prevalence is
      compared to changes in diet that have occurred in the same period. RESULTS: The
      results show that the mean weight and height of both men and women have been
      increasing during the study period. However, weight has increased more than can
      be accounted for by increased height, resulting in increased BMI. At the same
      time, the prevalence of overweight and obesity have increased, the relative
      increase in obesity far exceeding the relative increase in overweight. The
      prevalence of obesity more than doubled in both age groups of women during the
      study period, according to trend analyses. At the end of the period, almost 15%
      (95% confidence interval (CI), 9-22%) in the younger group of women and 25% (95%
      CI, 17-34%) in the older group were classified as obese. In the younger group of
      men, the prevalence of obesity almost doubled, while the observed increase in the
      older group was not statistically significant, according to trend analyses. The
      prevalence of obesity in the final period was about 19% (95% CI, 13-27%) and 17%
      (95% CI, 11-25%) in the younger and older groups of men, respectively. According
      to the food supply statistics there have been insignificant changes in the
      consumption of energy nutrients during the period. CONCLUSIONS: Overweight and
      obesity are becoming more common among middle-aged men and women in Reykjavik,
      during the period 1975-1994 and the rate of increase being comparable to that
      observed in many Western countries. It is urgent to respond to this problem by
      promoting a healthier lifestyle, both with respect to diet and physical activity.

PMID- 17019003
TI  - [The channels for important new knowledge to medical doctors. The case of
      Helicobacter pylori and stomach and duodenal ulcers.].
AB  - A retrospective survey of the flow of information to medical doctors as regards
      the relationship between Helicobacter pylori and stomach and duodenal ulcer and
      other gastrointestinal diseases. This is the Icelandic part of a joint study in
      five Nordic countries. OBJECTIVE: The objective of the research was to assess the
      effectiveness of different sources of information, to measure the length of time
      it takes for the information to spread and influence medical practice. MATERIAL
      AND METHODS: The information was collected with the help of questionnaires that
      were sent to 159 general practitioners (GP) and 110 physicians in three medical
      specialities. Among the questions asked were when and how the information had
      reached the respondents and when and how it had influenced their medical
      practices. RESULTS: The knowledge about Helicobacter pylori had generally reached
      medical doctors six to eight years after it first appeared in the medical
      journals and had three years later led to changes in the routine examinations and
      treatment. The specialists got the news one to three years earlier than the GPs
      and also started to prescribe antibiotics one to three years earlier. The most
      frequently cited source of information was international medical journals, then
      scientific conferences, colleagues and The Icelandic Medical Journal. The most
      important source was considered to be international medical journals, then
      scientific conferences and colleagues. A certain difference was found between GPs
      and the specialist doctors. More GPs said they had got information from the
      pharmaceutical industry or through The Icelandic Medical Journal and relied on
      clinical diagnosis. More specialist doctors considered the most important source
      of new knowledge to be the colleagues, they also said they used endoscopy and
      took tissue samples more often and more often considered it correct to do so.
      CONCLUSIONS: Only a decade after the first reports on Helicobacter pylori
      appeared in medical journals most Icelandic doctors had got the knowledge and
      were prescribing appropriate treatment, the specialist doctors in the lead.
      International medical journals spread the news most effectively but The Icelandic
      Medical Journal played only a minor role. The question is if the process could
      have been accelerated any further by some more hitting Icelandic news and by more
      definite initiative in framing guidelines.

PMID- 17019005
TI  - [Incidence of disability in Iceland before and after introduction of a new method
      of disability evaluation.].
AB  - OBJECTIVE: To assess changes in disability evaluation, since the introduction on
      September 1st 1999 of a new assessment method based on the British functional
      capacity evaluation, "All work test". Previously, the disability assessment was
      based on the applicant's medical, social and financial circumstances. MATERIAL
      AND METHODS: The study includes all those having their disability assessed for
      the first time at the State Social Security Institute of Iceland in 1997, 1998
      and 2000. Information was obtained from the disability register on degree of
      disability, gender, age and primary diagnoses. RESULTS: After the introduction of
      the new assessment method, there has been a significant increase in the number of
      women who have disability more then 75% (p<0.0001). This increase occurs amongst
      women older than 30 years, having musculoskeletal disorders (mainly soft tissue
      disorders). There has also been a slight (statistically insignificant) increase
      in more than 75% disability amongst men (p=0.25). The number of people who have
      had their disability evaluated as 50-65% has decreased (p<0.0001). No significant
      change in the total number of new disability pensioners (having their disability
      assessed as being more than 75% or 50-65%) was observed. CONCLUSIONS: The new
      method of disability assessment has resulted in a significant rise in the number
      of women who have had their disability assessed as being more than 75%, but there
      has not been a rise in the total number of new disability pensioners, as the
      increased number of women with the higher degree of disability has been balanced
      by a significant fall in the number of new disability pensioners with the lower
      degree of disability.

PMID- 17019004
TI  - [The effect of dietary fish oil on bacterial growth in vivo.].
AB  - OBJECTIVE: Epidemiological studies have indicated that high intake of w-3 fatty
      acids influence various diseases such as cardiovascular diseases and autoimmune
      disorders. These fatty acids are essential in the diet since the body can not
      form them de novo. Fish oil is rich in w-3 fatty acids but the w-3 content of
      vegetable oil is low. The research group has shown increased survival of mice fed
      cod liver oil enriched diet versus mice fed corn oil enriched diet when infected
      with Klebsiella pneumoniae intramuscularly. In the present study we investigated
      the effect of dietary fish oil on bacterial growth in vivo. MATERIAL AND METHODS:
      Mice were fed fish oil enriched diet and a control group was fed corn oil
      enriched diet for six weeks and then the mice were infected with Klebsiella
      pneumoniae intramuscularly. The mice were sacrificed at various time intervals
      and bacteria were counted in blood and in the infected muscle. RESULTS: The
      bacteria count in blood and tissue was not significantly different between the
      two groups although a trend was noted towards more growth in the control group.
      CONCLUSIONS: We conclude that fish oil does not significantly affect bacterial
      growth in vivo. Hopefully, future research will reveal the pathophysiological
      effect of fish oil.

PMID- 17019006
TI  - [New face of the world after the attack on the twin towers in New York
      [Editorial].].

PMID- 17019007
TI  - [Resuscitation in the community [Editorial].].

PMID- 17019008
TI  - [Attitude of the Icelandic population towards performing cardiopulmonary
      resuscitation on strangers in the pre-hospital setting.].
AB  - OBJECTIVE: Initiation of bystander cardiopulmonary resuscitation (CPR) is
      directly linked to the outcome of cardiac arrest in the community. Recent reports
      have indicated a reluctance among witnesses to perform CPR on strangers
      especially mouth to mouth ventilation. The status of this in Iceland is unknown.
      The objective of this study was to assess the attitude of Icelanders towards
      bystander CPR. MATERIAL AND METHODS: A telephone survey was conducted on 1200
      randomly selected Icelanders, aged 16-75 years, with regard to their attitude
      towards pre-hospital CPR on strangers. A total of 804 (70.1%) chose to
      participate. RESULTS: A large number had received some kind of training in CPR
      (73%), wheras only 6% had actually participated in CPR. In accordance, 50%
      thought they would be able to perform chest compressions adequately and 55% mouth
      to mouth ventilation. A total of 491 (65%) would likely volunteer to perform
      chest compressions on a stranger, while 178 (24%) would not and 84 (11%) were
      undecided. Similarly, 473 (64%) would likely volunteer to perform mouth to mouth
      ventilation on a stranger. One hundred seventy seven (24%) would not and 93 (12%)
      were unsure. An overwhelming majority, 620 (81%) said it would not make any
      difference regarding their participation in CPR if the procedure was simplified
      and included only chest compressions but not mouth to mouth ventilation.
      CONCLUSIONS: Icelanders have a very positive attitude towards bystander CPR, over
      two thirds have had some kind of CPR instruction and a large majority has no
      aversion towards performing mouth to mouth ventilation on strangers. These
      results are in contrast to similar data from the United States.

PMID- 17019010
TI  - [Homocysteine, folate and cobalamin in Icelandic men and women.].
AB  - OBJECTIVE: To determine reference intervals and interquartile ranges for total
      homocysteine (Hcy) folate and cobalamin in Icelandic men and women and to
      evaluate the correlation of Hcy to serum levels of the vitamins folate and
      cobalamin. MATERIAL AND METHODS: Blood samples were collected from 449
      individuals over a period of three months, 291 men (mean age 48.3 years) and 158
      women (mean age 49.8 years). Plasma Hcy was measured by a HPLC method with
      fluorescence detection; folate and cobalamin levels in serum were measured by an
      electroimmunochemical method on an ELECSYS system from Roche. RESULTS: The
      reference interval for Hcy, between 2.5% and 97.5% fractiles, estimated by
      parametric statistics, are 6.2-17.5 micromol/L for men and 4.8-14.1 micromol/L
      for women. Similarly the 95% reference intervals for folate and cobalamin were
      estimated using parametric statistics. A significant negative correlation was
      found between concentrations of folate and Hcy for both men and women (p<0.01)
      with a correlation coefficient of -0.39 and also between cobalamin and Hcy where
      the correlation coefficient is -0.20. CONCLUSIONS: Reference interval for Hcy
      from the general presumed healthy population is estimated here for the first time
      in Icelandic men and women and will be of value in cardiovascular risk
      assessments. The negative correlation between Hcy and folate and also Hcy and
      cobalamin, is in agreement with results from other studies and suggests that an
      improved vitamin status might be beneficial in lowering Hcy in a section of the
      population as has been suggested in numerous studies in other countries.

PMID- 17019009
TI  - [Fungemia and other invasive fungal infections in Icelandic children. A
      nationwide study.].
AB  - INTRODUCTION: Invasive fungal infections are increasing in incidence. Among those
      who are at increased risk of fungal blood stream infections (fungemia) and
      disseminated fungal infections are premature infants and immunosuppressed
      children. These infections are associated with high morbidity and mortality.
      Invasive fungal infections have not yet been studied in Iceland. MATERIAL AND
      METHODS: We studied all cases of fungemia and/or disseminated fungal infections
      in Icelandic children (16 years) during a 20 year period. Histopathology reports
      and autopsies were reviewed. Information on predisposing factors, symptoms,
      treatment and outcome was collected. All obtainable fungal blood stream isolates
      were subcultured and their susceptibility to common antifungals determined.
      RESULTS: In the 20 year period from 1980-1999, 19 episodes of invasive fungal
      infections were diagnosed in 18 infants and children in Iceland. Twelve episodes
      of fungemia occured in 11 children and the nationwide annual incidence increased
      from 0.28 to 1.90 cases/100,000/year (p=0.037) during the study period. Half of
      the children were premature infants. All patients had a central venous catheter
      at the time of blood culture and most had received intravenous antibiotics or
      corticosteroids. Candida albicans was the most commonly isolated species (nine of
      12 episodes, 75%). In addition to patients with fungemia, three children were
      diagnosed with disseminated fungal infection by histology or autopsy. Two cases
      of fungal meningitis, without fungemia, were identified. Furthermore, two
      children had invasive infections with Aspergillus fumigatus and both patients
      survived. Three children (3/16; 19%) with invasive Candida-infections died.
      CONCLUSIONS: In this study of invasive fungal infections among Icelandic children
      we demonstrate that the incidence of fungemia has risen significantly in the past
      20 years. Diagnosis of invasive fungal infections can be complicated and negative
      blood cultures do not exclude disseminated infection. Given the high attributable
      mortality, timely diagnosis and aggressive treatment is extremely important.

PMID- 17019011
TI  - [Common causes of sleep disturbances in Icelandic children who undergo sleep
      studies.].
AB  - INTRODUCTION: Sleep disturbances are common problems in children. Frequently,
      these problems are attributed to learned behavioral patterns, but little is known
      about organic causes of sleep disturbances in children. Obstructive sleep apnea
      (OSA) is a common cause of sleep disordered breathing in adults. Gastroesophageal
      reflux (GER) is also common in this population. Less is known about OSA and GER
      as potential causative agents of sleep disturbances in children, and these
      medical problems have not been addressed in Icelandic children. This study was
      designed to investigate the organic causes of sleep disordered breathing in
      Icelandic children, evaluate their severity and possible therapies. MATERIAL AND
      METHODS: One hundred and ninty children who were referred to the Pediatric
      Department at Reykjavik Hospital due to sleep disturbances were hospitalized over
      night and a sleep study was recorded, using the sleep equipment, EMBLA. The
      latter machine has 16 channels that record informations about sleep patterns and
      breathing. The children were 0-18 years of age. Informations were collected from
      EEGs, EMGs, and eye movements to determine sleep stages, and with respiratory
      belts with sensors on the chest and abdomen as well as an air-flow sensor that
      measures airflow through the nose and mouth. When GER was suspected, a pH meter
      was inserted and the pH values were measured in the upper and lower parts of the
      esophagus. RESULTS: The results demonstrate that a large number of children who
      suffer from sleep disturbances have an underlying disease. Of 61 children who
      underwent a sleep study and were suspected to have OSA, 46 had a positive study
      that resulted in a change in therapy. In addition, 69 of 89 children who
      underwent pH measurements in the esophagus were diagnosed with GER which prompted
      changes in therapy. CONCLUSIONS: The study demonstrates that both OSA and GER are
      common problems in children with sleep disturbances. We conclude that sleep
      studies are important in the overall workup of children with sleep disturbances,
      and can provide valuable informations regarding the causes, prevalence and
      severity of these medical problems. Sleep studies also facilitate the selection
      of children who require specific treatments such as operation of the oropharynx
      or CPAP/BiPAP treatment for OSA, or drug therapy for GER.

PMID- 17019012
TI  - [Personal identifiability in the Health Sector Database.].
AB  - INTRODUCTION: Personal identifiability is a fundamental question in the debate
      about the Bill and Act on the Health Sector Database (HSD). If the data are
      personally identifiable, Iceland's international committments dictate that a
      priori consent be obtained from patients for the use of their health records
      data. The HSD Act presumes that one way encryption renders the data non
      personally identifiable and that therefore an a priori consent is not required.
      RESULTS: The history of the concept of personal identifiability during the debate
      on the HSD reveals changes made to the concept. In the first instance a reference
      was made to Recommendation R(97)5 of the Council of Europe Committee of Ministers
      which was changed by adopting a direct translation of the definition of personal
      data from the Directive 95/46/EC of the European Parliament and of the Council.
      These changes were made in response to the Data Protection Commission's opinion
      on the HSD Bill submitted to the Minister of Health that overturned the ideology
      previously used regarding indentifiability of persons. Information is
      identifiable if there exists a key and it makes no difference who holds the key.
      One way encryption was then adopted as a method that was supposed to mean that a
      key does not exist. Nevertheless, the database proponents now admit that a key
      exists. The making of keys for opening up the database is discussed. The database
      is a longitudinal collection and linkage of records on each individual and
      therefore the method of encryption must remain stable. Therefore, anyone with
      access to the method can easily make a lookup-table containing side by side the
      names and the personal numbers produced by the encryption. Although it may be
      hard to go from a personal number directly back to a name, given the table it
      always is possible to look up what personal number belongs to a certain person or
      what person stands behind a certain personal number. This is a key. If the method
      of encryption was lost or access to it was not available it would nevertheless be
      possible to make a key. The intention is to encrypt the genealogy of the entire
      nation using the same encryption method used for the HSD. The genealogy of the
      nation with names is also generally available. The patterns of family trees
      become unique when one family is connected to another through marriage and
      childbirth. A comparison of the encrypted genealogy containing personal numbers
      with the same genealogy containing names is therefore a method for making a key.
      Finally a key can be made from the context of general information. Even if the
      names were irreversibly removed there will be enough available bits of general
      information connected to a personal number to allow re-identification of the
      person in a large number of instances. This amounts to making a key. CONCLUSIONS:
      The information in the Health Sector Database is personal information. Therefore
      it is both right and reasonable to obtain an a priori consent of patients for the
      transfer of their health data to the database as Iceland's international
      obligations stipulate. Anything less is unreasonable.

PMID- 17019013
TI  - [Acts of terror with the aid of contagion and poison [Editorial].].

PMID- 17019014
TI  - [The pill at age forty [Editorial].].

PMID- 17019015
TI  - [The current concept of primary IgA deficiency and its prevalence in Iceland.].
AB  - IgA deficiency is among the most common primary immune deficiency known. Its
      prevalence, ranging from 1/324-1/1850, depends upon the study group geographic
      location and its ethnicity. IgA deficiency is commonly associated with other
      immune defects such as IgG2, and IgG4 deficiency. In addition, ataxia
      telangiectasia has been associated with IgA deficiency as well. The clinical
      significans of IgA deficiency is presently unclear. However, increased
      susceptibility to atopy, autoimmunity, infections and cancer has been reported.
      Furthermore, majority of these diseases are bound to the mucosal surfaces; the
      organ where IgA is thought to have its most protective role. Recent studies
      focusing on the genealogy of primary IgA deficiency have found linkages to
      chromosome 6, 14, 18 and 22. In addition, a link to certain HLA haplotypes has
      been reported. Thus, further studies into the immunogenetics of IgA deficiency
      are needed, particularly focusing upon the question why some individuals with IgA
      deficiency are prone to diseases whereas others are not. In this article some of
      these questions are addressed, and the current literature on the topic reviewed.

PMID- 17019016
TI  - [Calcaneal ultrasound as a screening test for osteoporosis.].
AB  - INTRODUCTION: Dual energy X-ray absorptiometry (DEXA) has been the cornerstone in
      the diagnosis of osteoporosis. Quantitative ultrasound (QUS) of calcaneus is easy
      to perform and cheaper than DEXA but prior studies have shown a limited
      correlation and agreement between the two tests. The purpose of this study was to
      assess calcaneal ultrasound as a screening test for osteoporosis. MATERIAL AND
      METHODS: Two-hundred-ninety-seven 70-years-old Icelandic women underwent a DEXA
      measurement of lumbar spine, left hip and whole body as well as QUS of left
      calcaneus. We assessed the correlation and agreement between the two tests and
      searched for the optimal cut-off point in QUS for the diagnosis of osteoporosis
      from sensitivity and specificity calculations and ROC curves. We also examined
      correlation between DEXA or QUS and anthropometric or biochemical measurements of
      bone markers. Finally, we compared the women who had sustained a fracture to
      those who had not with regard to DEXA and QUS. RESULTS: The correlation between
      DEXA at different sites and QUS ranged form 0.40 to 0.57 (Spearman's correlation
      coefficient) with the best correlation for left hip DEXA. The best
      sensitivity/specificity relationship of QUS in diagnosis of osteoporosis (WHO
      criteria) at the hip, was found for QUS T-score of -2.5; sensitivity 91.7%,
      specificity 49.0%, positive predictive value 25.8% and negative predictive value
      of 96.8%. Kappa-statistic showed a marginal agreement between the two tests
      (k=0.25, p<0.01). The correlation was generally stronger between DEXA and serum
      biochemical markers of bone turnover or weight than between QUS and these
      parameters but was in the same direction. Mean hip bone density and QUS results
      were lower in the group of women with history of fractures than the others,
      0.731+/-0.112 g/cm(2) vs. 0.779+/-0.130 g/cm(2) (T-score -1.18+/-1.18 vs. -1.61+/
      1.20, p=0.001) and T-score -3.12+/-0.94 vs. -2.40+/-1.22 (p=0.0001) for QUS.
      CONCLUSIONS: Even though QUS is not a good test for diagnosing osteoporosis as
      defined by WHO criteria, it is a reasonable screening test with good sensitivity
      and fair specificity when using T-score of -2.5 as the cut-off point.

PMID- 17019017
TI  - [Changes in myocardial infarction incidence and mortality in Iceland.].
AB  - INTRODUCTION: According to public health reports ischaemic heart disease was an
      uncommon cause of death in Iceland at the beginning of the last century. This
      death rate increased steadily until the ninety-eighties whereafter it leveled off
      and started to decline. The objective of the present study is to assess in detail
      the changes in myocardial infarction attack, incidence and death rate as well as
      case fatality. MATERIAL AND METHODS: Crude death rate from ischaemic heart
      disease is available from the Statistical Bureau of Iceland from 1911 to 1996 and
      age and sex standardized death rate from 1951. In this paper, however, the
      material is mainly from the MONICA Project, a multinational study of myocardial
      infarction under the auspices of the World Health Organization. The study, in
      which Iceland has participated since 1981, registers all myocardial infarctions
      in people aged 25-74 years in the whole country. The registration is performed
      according to standardized criteria and external quality control was applied
      throughout by WHO designated quality control centers. The registration now covers
      the period 1981-1998. RESULTS: The crude death rate in ischaemic heart disease in
      both sexes combined increased steadily until about 1980 when it accounted for
      about 30% of deaths. Age and sex specific death rate from these diseases
      increased from 1951 to about 1970, leveled off for the next 10 years and has
      since decreased. The MONICA data show a decline of death rate from myocardial
      infarction of 57% in men aged 25-74 during 1981-1998 and a 51% decline in women.
      Incidence rate has declined by 40% and 34% in men and women respectively and
      attack rate by 49% and 44%. Incidence, death rate and case fatality in myocardial
      infarction in Iceland compares favorably with other European countries.
      CONCLUSIONS: Myocardial infarction incidence and death rates have been declining
      in Iceland during the last two decades. Case fatality is now among the lowest
      compared to other countries. Preventive measures are most likely to further
      reduce incidence and death rates in myocardial infarction in Iceland.

PMID- 17019018
TI  - [The communication between doctors and the pharmaceutical firms [Editorial].].

PMID- 17019019
TI  - [The pharmaceutical industry and the medicine [Editorial].].

PMID- 17019020
TI  - [Sudden noncardiac arrest out-of-hospital in the Reykjavik area 1987-1999.].
AB  - PURPOSE: The purpose of this investigation was to study specifically those cases
      of sudden death out-of-hospital in the Reykjavik area that were due to non
      cardiac causes the last 13 years, from January 1987 to December 31, 1999.
      MATERIAL AND METHODS: The doctors of the emergency ambulance have kept detailed
      files for all cases of sudden death according to international system of
      documentation, the Utstein protocol. The cases were divided into two major
      groups, i.e. on one hand cases due to outer causes and on the other hand cases
      due to inner causes. Outer causes included suicide, intoxication by drugs,
      trauma, drowning and cases due to asphyxia. Inner causes included various types
      of bleeding, hypoxia, cot death and various diseases other than heart disease.
      RESULTS: From 738 cases 140 or 19% were thought to be due to sudden non-cardiac
      death. Ninety-two cases of those 140 or 66% were due to outer causes. Inner
      causes were diagnosed in 48 (34%) cases. Mean age was 46 years (standard
      deviation, SD: 24.3 years). Men were 85 of the 140 cases (61%) and women 55
      (39%). Mean response time was five minutes. Of the 140 individuals only nine (6%)
      survived, of those four had sustained near-drowning, four near suffocation and
      one drug intoxication. CONCLUSIONS: In this study the data were reported in
      accordance with the Utstein protocol and therefore drug intoxication and suicide
      are not grouped together. However, most if not all cases of drug intoxication
      appear to have occurred in an attempt of suicide. Except for cardiac disease drug
      intoxication and suicides were together the most common causes of sudden death
      out-of-hospital in those instances attended by the crew of the emergency
      ambulance. The results of resuscitation attempts are much worse when the cause
      for sudden death is non-cardiac. Survival was relatively best in cases of
      "suffocation" or "drowning".

PMID- 17019021
TI  - [Educational level, occupation and income of those who became disability
      pensioners in Iceland in the year 1997.].
AB  - INTRODUCTION: All claims for disability benefits in Iceland are managed by the
      State Social Security Institute of Iceland. The decision to grant a claimant
      disability benefits was until September 1999 mainly based on medical certificates
      but social and economic factors were also taken into consideration. As
      information on social and economic conditions in medical certificates is limited
      it was decided to investigate these factors particularly. In this paper a
      comparison of educational level, employment, and income is made between new
      recipients of disability benefits and a random sample of the Icelandic nation.
      MATERIAL AND METHODS: All new recipients of disability benefits (full disability
      pension, partial disability pension and rehabilitation pension) in 1997 were
      contacted by phone and asked to answer a questionnaire. Their answers were
      compared with those obtained in a national survey carried out by the Institute of
      Social Sciences at the University of Iceland in 1996 and 1997 with a sample
      representing accurately the Icelandic population in terms of gender, age and
      place of residence. Information about average income of disability pensioners was
      obtained and compared to that of people in employment. RESULTS: Educational level
      of those receiving disability benefits was considerably lower than expected in
      comparison with the population and unskilled workers were overrepresented.
      Contrary to what might be expected a larger proportion of the recently disabled
      have been employed at some time than is the case for the national sample, even
      though 63.6% of the new disability pensioners were women. Considerable number of
      those receiving disability benefits were still in employment, particularly those
      with partial disability pension. Mean monthly income of Icelanders participating
      in the labour market was almost twice that received by those on disability
      benefits. CONCLUSIONS: Since lower educational level and more restricted
      employment opportunities characterize disability pensioners as compared to the
      nation, it seems likely that more varied occupational rehabilitation and
      educational opportunities could improve the situation of those who have had to
      leave the labour market because of ill health, lack of education and poor working
      conditions.

PMID- 17019022
TI  - [Hirschprung' disease in Iceland 1969-1998.].
AB  - INTRODUCTION: Hirschprung s disease (HD) is a congenital disease characterized by
      the absence of myenteric and submucosal ganglion cells in the distal alimentary
      tract and results in decreased motility in the affected bowel segment. The
      purpose of this study was to review the incidence, presentation, treatment and
      operative results in children with Hirschprung's disease in Iceland. MATERIAL AND
      METHODS: Thirteen infants with Hirschprung s disease (11 boys and two girls) were
      treated in Landspitalinn University Hospital between January 1969 and December
      1998. The records of these patients were reviewed retrospectively. RESULTS: The
      incidence of Hirschprung's disease in Iceland is 1/10,000 and 85% of those are
      boys. All the infants were born full term. No family history and no associated
      abnormalities were noted. The mean age at first admission was 20 (1-136) days and
      mean age at diagnosis was 166 (5-623) days. Swenson's pull-through (two- or three
      stage procedure) was carried out in all patients at the mean age of 18.6 months.
      The extent of aganglionosis was rectosigmoid colon in 10 patients (77%) and one
      patient had total colonic aganglionosis. Postoperative complications occurred in
      seven patients (53%), adhesion ileus being the most common complication. Long
      term bowel function was satisfactory in 85% of the patients. CONCLUSIONS: The
      incidence of Hirschprung's disease in Iceland is low. Mean age at diagnosis is
      six months. Sixty percent of the children are discharged with a wrong diagnosis
      after first admission to hospital and this could be improved by diagnosing the
      disease at an earlier stage. Postoperative complications are common but no deaths
      occurred. Bowel function following definitive correction is good compared to
      other studies.

PMID- 17019023
TI  - [The tropical rat mite Ornithonyssus bacoti attacks humans in Iceland.].
AB  - In the summer of 2001 the obligate, intermittent tropical rat mite Ornithonyssus
      bacoti attacked humans in an Icelandic household where infected Mongolian gerbils
      (Meriones unguiculatus), bought in a local pet shop, had been kept for few
      months. After a rapid proliferation the mite started attacking the humans living
      in the house. A boy sharing room with the pets suffered from extensive
      dermatitis. Optimal conditions for O. bacoti are at 24-26 degrees C and a
      relative humidity of 47%. Similar conditions frequently occur indoors in
      Icelandic premises. Therefore, if O. bacoti has been noticed indoors, necessary
      measures should be undertaken to immediately eliminate the pest.

PMID- 17019024
TI  - Direct aperture optimization of breast IMRT and the dosimetric impact of
      respiration motion.
AB  - We have studied the application of direct aperture optimization (DAO) as an
      inverse planning tool for breast IMRT. Additionally, we have analysed the impact
      of respiratory motion on the quality of the delivered dose distribution. From
      this analysis, we have developed guidelines for balancing the desire for a high
      quality optimized plan with the need to create a plan that will not degrade
      significantly in the presence of respiratory motion. For a DAO optimized breast
      IMRT plan, the tangential fields incorporate a flash field to cover the range of
      respiratory motion. The inverse planning algorithm then optimizes the shapes and
      weights of additional segments that are delivered in combination with the open
      fields. IMRT plans were generated using DAO with the relative weights of the open
      segments varied from 0% to 95%. To assess the impact of breathing motion, the
      dose distribution for the optimized IMRT plan was recalculated with the isocentre
      sampled from a predefined distribution in a Monte Carlo convolution/superposition
      dose engine with the breast simulated as a rigid object. The motion amplitudes
      applied in this study ranged from 0.5 to 2.0 cm. For a range of weighting levels
      assigned to the open field, comparisons were made between the static plans and
      the plans recalculated with motion. For the static plans, we found that uniform
      dose distributions could be generated with relative weights for the open segments
      equal to and below 80% and unacceptable levels of underdosage were observed with
      the weights larger than 80%. When simulated breathing motion was incorporated
      into the dose calculation, we observed a loss in dose uniformity as the weight of
      the open field was decreased to below 65%. More quantitatively, for each 1%
      decrease in the weight, the per cent volume of the target covered by at least 95%
      of the prescribed dose decreased by approximately 0.10% and 0.16% for motion
      amplitudes equal to 1.5 cm and 2.0 cm, respectively. When taking into account the
      motion effects, the most uniform and conformal dose distributions were achieved
      when the open segment weights were in the range of 65-80%. Within this range,
      high-quality IMRT plans were produced for each case. The study demonstrates that
      DAO with tangential fields provides a robust and efficient technique for breast
      IMRT planning and delivery when the open segment weight is selected between 65%
      and 80%.

PMID- 17019025
TI  - Refractive index measurement for biomaterial samples by total internal
      reflection.
AB  - The refractive index of biological tissue is a fundamental parameter in
      applications of optical diagnosis and laser treatments. In the present work, the
      refractive indices and thermo-optic coefficients of some basic biomaterials, such
      as blood plasma, haemoglobin solution and lipid membrane, were studied by the
      method of total internal reflection at the wavelengths of 532 and 632.8 nm that
      are the most frequently used laser wavelengths in the biomedical field. The
      effects of the sample concentration and the temperature on refractive index were
      measured, and empirical relationships were summarized, accompanied by a
      theoretical explanation based on molecular polarization theory. The results
      provide some fundamental data for the refractive indices of these biomaterials
      under variant conditions, and also demonstrate that the total internal reflection
      method is a feasible and reliable way to measure the refractive indices of
      biological samples.

PMID- 17019026
TI  - Acoustic response of compliable microvessels containing ultrasound contrast
      agents.
AB  - The existing models of the dynamics of ultrasound contrast agents (UCAs) have
      largely been focused on an UCA surrounded by an infinite liquid. Preliminary
      investigations of a microbubble's oscillation in a rigid tube have been performed
      using linear perturbation, under the assumption that the tube diameter is
      significantly larger than the UCA diameter. In the potential application of drug
      and gene delivery, it may be desirable to fragment the agent shell within small
      blood vessels and in some cases to rupture the vessel wall, releasing drugs and
      genes at the site. The effect of a compliant small blood vessel on the UCA's
      oscillation and the microvessel's acoustic response are unknown. The aim of this
      work is to propose a lumped-parameter model to study the interaction of a
      microbubble oscillation and compliable microvessels. Numerical results
      demonstrate that in the presence of UCAs, the transmural pressure through the
      blood vessel substantially increases and thus the vascular permeability is
      predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with
      a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small
      changes in the microbubble oscillation frequency and maximum diameter are
      observed. When the ultrasound pressure increases, strong nonlinear oscillation
      occurs, with an increased circumferential stress on the vessel. For a compliable
      vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is
      predicted to be sufficient for microbubble fragmentation regardless of the vessel
      diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient
      to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative
      pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold
      for vascular rupture in a small (diameter less than 15 microm) compliant vessel.
      As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and
      vessel dilation decrease; however the circumferential stress is predicted to
      increase. Decreasing the vessel size or the centre frequency increases the
      circumferential stress. For the two frequencies considered in this work, the
      circumferential stress does not scale as the inverse of the square root of the
      acoustic frequency va as in the mechanical index, but rather has a stronger
      frequency dependence, 1/va.

PMID- 17019027
TI  - Design and characterization of a digital image acquisition system for whole
      specimen breast histopathology.
AB  - We have developed a digital histopathology imaging system capable of producing a
      three-dimensional (3D) representation of histopathology from an entire lumpectomy
      specimen. The system has the potential to improve the accuracy of surgical margin
      assessment in the treatment of breast cancer by providing finer sampling and 3D
      visualization. A scanning light microscope was modified to allow digital
      photomicrography of a stack of large (up to 120x170 mm2) histology slides cut
      serially through the entire specimen. The images are registered and displayed in
      2D and 3D. The design of the system, which reduces or eliminates the appearance
      of 'tiling' and 'seam' artefacts inherent in the scanning method, is described
      and its resolution, contrast/noise and coverage properties are characterized
      through measurements of the modulation transfer function (MTF), depth of field
      (DOF) and signal difference to noise ratio (SDNR). The imaging task requires a
      lateral resolution of 5 microm, an SDNR of 5 between relevant features, 'tiling
      artefact' at a level below the detectability threshold of the eye, and 'seam
      artefact' of less than 5-10 microm. The tests demonstrate that the system is
      largely adequate for the imaging task, although further optimizations are
      required to reduce the degradation of coverage incurred by seam artefact.

PMID- 17019028
TI  - Principal component, Varimax rotation and cost analysis of volume effects in
      rectal bleeding in patients treated with 3D-CRT for prostate cancer.
AB  - We investigate the utility of principal component analysis as a tool for
      obtaining dose-volume combinations related to rectal bleeding after radiotherapy
      for prostate cancer. A direct implementation of principal component analysis
      reduces the number of degrees of freedom from the patient's dose-volume
      histograms that are associated with bleeding. However, when low-variance
      principal components are strongly correlated to outcome, their interpretation is
      problematic. A Varimax rotation is employed to aid in interpretability of the low
      variance principal components. This procedure brings us closer to finding unique
      dose-volume combinations related to outcome but reintroduces correlation,
      requiring analysis of the overlap of information contained in such modes.
      Finally, we present examples of cost-benefit analyses for candidate dose-volume
      constraints for use in treatment planning.

PMID- 17019029
TI  - Measurement of the x-ray mass energy-absorption coefficient of air using 3 keV to
      10 keV synchrotron radiation.
AB  - For the first time absolute photon mass energy-absorption coefficients of air in
      the energy range 3 keV to 10 keV have been measured with relative standard
      uncertainties less than 1%, significantly smaller than those of up to 5% assumed
      hitherto for calculated data. Monochromatized synchrotron radiation was used to
      measure both the total radiant energy by means of silicon photodiodes calibrated
      against a cryogenic radiometer and the fraction of radiant energy that is
      deposited in dry air by means of a free air ionization chamber. The measured
      ionization charge was converted into energy absorbed in air by calculated
      effective W values of photons as a function of their energy based on new
      measurements of the W values in dry air for electron kinetic energies between 1
      keV and 7 keV, also presented in this work. The measured absorption coefficients
      were compared with state-of-the art calculations and found to agree within 0.7%
      with data calculated earlier by Hubbell at energies above 4 keV but were found to
      differ by values up to 2.1% at 10 keV from more recent calculations of Seltzer.

PMID- 17019030
TI  - Organ and effective doses in newborn patients during helical multislice computed
      tomography examination.
AB  - In this study, two computational phantoms of the newborn patient were used to
      assess individual organ doses and effective doses delivered during head, chest,
      abdomen, pelvis, and torso examinations using the Siemens SOMATOM Sensation 16
      helical multi-slice computed tomography (MSCT) scanner. The stylized phantom used
      to model the patient anatomy was the revised ORNL newborn phantom by Han et al
      (2006 Health Phys.90 337). The tomographic phantom used in the study was that
      developed by Nipper et al (2002 Phys. Med. Biol. 47 3143) as recently revised by
      Staton et al (2006 Med. Phys. 33 3283). The stylized model was implemented within
      the MCNP5 radiation transport code, while the tomographic phantom was
      incorporated within the EGSnrc code. In both codes, the x-ray source was modelled
      as a fan beam originating from the focal spot at a fan angle of 52 degrees and a
      focal-spot-to-axis distance of 57 cm. The helical path of the source was
      explicitly modelled based on variations in collimator setting (12 mm or 24 mm),
      detector pitch and scan length. Tube potentials of 80, 100 and 120 kVp were
      considered in this study. Beam profile data were acquired using radiological film
      measurements on a 16 cm PMMA phantom, which yielded effective beam widths of 14.7
      mm and 26.8 mm for collimator settings of 12 mm and 24 mm, respectively. Values
      of absolute organ absorbed dose were determined via the use of normalization
      factors defined as the ratio of the CTDI(100) measured in-phantom and that
      determined by Monte Carlo simulation of the PMMA phantom and ion chamber. Across
      various technique factors, effective dose differences between the stylized and
      tomographic phantoms ranged from +2% to +9% for head exams, -4% to -2% for chest
      exams, +8% to +24% for abdominal exams, -16% to -12% for pelvic exams and -7% to
      0% for chest-abdomen-pelvis (CAP) exams. In many cases, however, relatively close
      agreement in effective dose was accomplished at the expense of compensating
      errors in individual organ dose. Per cent differences in organ dose between the
      stylized and tomographic phantoms at 120 kVp and 12 mm collimator setting ranged
      from -25% (skin) to +164% (muscle) for head exams, -92% (thyroid) to +98%
      (ovaries) for chest exams, -144% (uterus) to +112% (ovaries) for abdominal exams,
      -98% (SI wall) to +20% (thymus) for pelvic exams and -60% (extrathoracic airways)
      to +13% (ovaries) for CAP exams. Better agreement was seen between the two
      phantom types for organs entirely within the scan field. In these cases,
      corresponding per cent differences in organ absorbed dose did not vary more than
      17%. For all scans, the effective dose was found to range approximately 1-13 mSv
      across the scan parameters and scan regions. The largest effective dose occurred
      for CAP scans at 120 kVp.

PMID- 17019031
TI  - An empirical method for the determination of wall perturbation factors for
      parallel-plate chambers in high-energy electron beams.
AB  - The calibration of ion chambers in high-energy electron beams in terms of
      absorbed dose to water at the National Physical Laboratory requires knowledge of
      the ratio of perturbation factors in graphite and water phantoms. During a review
      of data required for the NPL calibration procedure an empirical model was
      developed to calculate the perturbation due to the rear wall, pwall, of a well
      guarded ion chamber in a high-energy electron beam. The overall uncertainty in
      this method is estimated to be 0.4%, which is the lowest value reported to date.
      The model reproduces measured data at the 0.1% level or better and indicates that
      the NACP ion chamber has a nonzero perturbation factor in electron beams due to
      backscatter from the rear wall. The effect is small (<0.5%) at high energies
      (R50>4 cm, E0>10 MeV) but becomes large at low energies-up to 1.4% at E0=4 MeV
      (R50=1.2 cm). The model indicates that there is a nonzero correction for the NACP
      chamber in both a graphite and water phantom and that material adjacent to the
      air cavity has a significant effect on the measured ionization. These values are
      consistent with previous measurements and recent Monte Carlo calculations. The
      model could be used in the design of ion chambers and in the estimation of
      corrections for non-homogeneous systems, especially in the absence of accurate
      Monte Carlo simulations.

PMID- 17019032
TI  - Dosimetric impact of a CT metal artefact suppression algorithm for proton,
      electron and photon therapies.
AB  - Accurate dose calculation is essential to precision radiation treatment planning
      and this accuracy depends upon anatomic and tissue electron density information.
      Modern treatment planning inhomogeneity corrections use x-ray CT images and
      calibrated scales of tissue CT number to electron density to provide this
      information. The presence of metal in the volume scanned by an x-ray CT scanner
      causes metal induced image artefacts that influence CT numbers and thereby
      introduce errors in the radiation dose distribution calculated. This paper
      investigates the dosimetric improvement achieved by a previously proposed x-ray
      CT metal artefact suppression technique when the suppressed images of a patient
      with bilateral hip prostheses are used in commercial treatment planning systems
      for proton, electron or photon therapies. For all these beam types, this clinical
      image and treatment planning study reveals that the target may be severely
      underdosed if a metal artefact-contaminated image is used for dose calculations
      instead of the artefact suppressed one. Of the three beam types studied, the
      metal artefact suppression is most important for proton therapy dose
      calculations, intermediate for electron therapy and least important for x-ray
      therapy but still significant. The study of a water phantom having a metal rod
      simulating a hip prosthesis indicates that CT numbers generated after image
      processing for metal artefact suppression are accurate and thus dose calculations
      based on the metal artefact suppressed images will be of high fidelity.

PMID- 17019033
TI  - Ion recombination in parallel-plate free-air ionization chambers for synchrotron
      radiation.
AB  - The saturation characteristics of two sizes of parallel-plate free-air ionization
      chambers were investigated for synchrotron radiation at bending-magnet, wiggler
      and undulator beamlines of SPring-8. The gaps of the electrodes were 4.2 and 85
      mm. The monoenergetic photon energies ranged from 10 to 115.56 keV and the air
      kerma rates from 0.2 mGy s-1 to 150 kGy s-1. Ion recombination at the high dose
      rate was found to be smaller than that predicted by Boag's expression, which was
      based on volume recombination, and the difference increased with an applied
      electric field. In the high dose rate region, the reciprocal of the current was
      linear to the reciprocal of the electric field near saturation, which represented
      the occurrence of initial recombination and diffusion loss. At the low electric
      field and the low dose rate, the reciprocal of the current was linear to the
      reciprocal of the square of the electric field. The reduction of total ion
      recombination was attributed to the shift of the contribution from volume
      recombination to initial recombination and diffusion loss.

PMID- 17019034
TI  - Development of novel whole-body exposure setups for rats providing high
      efficiency, National Toxicology Program (NTP) compatibility and well
      characterized exposure.
AB  - This paper presents the design, optimization, realization and verification of
      novel whole-body exposure setups for rats. The setups operating at 902 MHz and
      1747 MHz provide highly efficient, National Toxicology Program (NTP) compatible
      and well-characterized exposures. They are compared to existing concepts of
      exposure setups with respect to efficiency, induced field uniformity, good
      laboratory practice (GLP) compatibility and cost. The novel exposure setup
      consists of a circular cascade of 17 sectorial waveguides excited by a novel loop
      antenna placed in the centre. The 70% overall efficiency of the exposure setup
      surpasses comparable values of existing setups. A field uniformity inside the
      phantom of more than 86% for the 1g cubical averaged specific absorption rate
      (SAR) within +/-5 dB of the whole-body SAR (WB-SAR) was attained. The uniformity
      of the exposure inside the setup, defined as the variation of the WB-SAR between
      animals, was better than +/-24%. Using only stainless steel, gold and
      polycarbonate in the vicinity of the animals ensured full GLP compatibility. The
      entire exposure system features fully automated computer controlled exposure and
      data monitoring, data storing and failure handling. Therefore, the proposed
      exposure system can be used to run blinded large scale, long-term exposure
      studies.

PMID- 17019035
TI  - Improvement in banding artefacts in four-dimensional computed tomography for
      radiotherapy planning.
AB  - Respiratory-gated CT (RGCT) and four-dimensional CT (4DCT) scan techniques cover
      consecutive segments of the respiratory cycle. However, motion artefacts may
      occur in fast respiratory phases such as mid-inhalation and -exhalation. CT
      imaging involves the use of a number of x-ray tube positions for each couch
      position. We investigated the fundamental nature of motion artefacts using a
      constant-velocity moving phantom in motion in the CT plane or perpendicular to
      the CT plane, and in pigs to simulate a human model. Artefacts and movement
      distance were evaluated in a moving phantom and artificially ventilated pigs with
      a 256-multi-detector row CT (256MDCT). The phantom moved in the CT plane or
      perpendicular to the CT plane with a constant velocity. Backprojection used
      variable initial backprojection angles (IBAs). The phantom length for motion
      perpendicular to the CT plane was independent of IBA but was represented by
      phantom diameter plus the distance of movement per gantry rotation. In contrast,
      that for the motion in the CT plane was dependent on IBA, as represented by
      phantom diameter plus the distance of movement per rotation for IBA perpendicular
      to the phantom movement direction, and phantom diameter plus half the distance of
      movement per gantry rotation for other IBAs. Results for volumetric CT images
      with different IBAs showed the presence of banding artefacts. Similar findings
      were seen in artificially ventilated pigs. Motion artefacts are unavoidable in
      both conventional CT and 256MDCT. Banding artefacts will be improved if the same
      IBAs at each couch position are accounted for during image reconstruction. This
      improvement will be beneficial in respiratory gated and 4D radiation therapies.

PMID- 17019036
TI  - Resolution of axial shear strain elastography.
AB  - The technique of mapping the local axial component of the shear strain due to
      quasi-static axial compression is defined as axial shear strain elastography. In
      this paper, the spatial resolution of axial shear strain elastography is
      investigated through simulations, using an elastically stiff cylindrical lesion
      embedded in a homogeneously softer background. Resolution was defined as the
      smallest size of the inclusion for which the strain value at the
      inclusion/background interface was greater than the average of the axial shear
      strain values at the interface and inside the inclusion. The resolution was
      measured from the axial shear strain profile oriented at 45 degrees to the axis
      of beam propagation, due to the absence of axial shear strain along the normal
      directions. The effects of the ultrasound system parameters such as bandwidth,
      beamwidth and transducer element pitch along with signal processing parameters
      such as correlation window length (W) and axial shift (DeltaW) on the estimated
      resolution were investigated. The results show that the resolution (at 45 degrees
      orientation) is determined by the bandwidth and the beamwidth. However, the upper
      bound on the resolution is limited by the larger of the beamwidth and the window
      length, which is scaled inversely to the bandwidth. The results also show that
      the resolution is proportional to the pitch and not significantly affected by the
      axial window shift.

PMID- 17019037
TI  - Tilted cone-beam reconstruction with row-wise fan-to-parallel rebinning.
AB  - Reconstruction algorithms for cone-beam CT have been the focus of many studies.
      Several exact and approximate reconstruction algorithms were proposed for step
      and-shoot and helical scanning trajectories to combat cone-beam related
      artefacts. In this paper, we present a new closed-form cone-beam reconstruction
      formula for tilted gantry data acquisition. Although several algorithms were
      proposed in the past to combat errors induced by the gantry tilt, none of the
      algorithms addresses the scenario in which the cone-beam geometry is first
      rebinned to a set of parallel beams prior to the filtered backprojection. We show
      that the image quality advantages of the rebinned parallel-beam reconstruction
      are significant, which makes the development of such an algorithm necessary.
      Because of the rebinning process, the reconstruction algorithm becomes more
      complex and the amount of iso-centre adjustment depends not only on the
      projection and tilt angles, but also on the reconstructed pixel location. In this
      paper, we first demonstrate the advantages of the row-wise fan-to-parallel
      rebinning and derive a closed-form solution for the reconstruction algorithm for
      the step-and-shoot and constant-pitch helical scans. The proposed algorithm
      requires the 'warping' of the reconstruction matrix on a view-by-view basis prior
      to the backprojection step. We further extend the algorithm to the variable-pitch
      helical scans in which the patient table travels at non-constant speeds. The
      algorithm was tested extensively on both the 16- and 64-slice CT scanners. The
      efficacy of the algorithm is clearly demonstrated by multiple experiments.

PMID- 17019038
TI  - Phase artefact reduction in magnetic resonance electrical impedance tomography
      (MREIT).
AB  - Cross-sectional conductivity imaging in magnetic resonance electrical impedance
      tomography (MREIT) requires the measurement of internal magnetic flux density
      using an MRI scanner. Current injection MRI techniques have been used to induce
      magnetic flux density distributions that appear in phase parts of the obtained MR
      signals. Since any phase error, as well as noise, deteriorates the quality of
      reconstructed conductivity images, we must minimize them during the data
      acquisition process. In this paper, we describe a new method to correct
      unavoidable phase errors to reduce artefacts in reconstructed conductivity
      images. From numerical simulations and phantom experiments, we found that the
      zeroth- and first-order phase errors can be effectively minimized to produce
      better conductivity images. The promising results suggest that this technique
      should be employed together with improved MREIT pulse sequences in future studies
      of high-resolution conductivity imaging.

PMID- 17019039
TI  - Interrelationships between electrical properties and microstructure of human
      trabecular bone.
AB  - Microstructural changes, such as reduction of trabecular thickness and number,
      are characteristic signs of osteoporosis leading to diminished bone strength.
      Electrical and dielectric parameters might provide diagnostically valuable
      information on trabecular bone microstructure not extractable from bone mineral
      density measurements. In this study, structural properties of human trabecular
      bone samples (n=26) harvested from the distal femur and proximal tibia were
      investigated using the computed microtomography (microCT) technique. Quantitative
      parameters, e.g. structural model index (SMI) or trabecular bone volume fraction
      (BV/TV), were calculated. In addition, the samples were examined electrically
      over a wide frequency range (50 Hz-5 MHz) using a two-electrode impedance
      spectroscopy set-up. Relative permittivity, loss factor, conductivity, phase
      angle, specific impedance and dissipation factor were determined. Significant
      linear correlations were obtained between the dissipation factor and BV/TV or SMI
      (|r| 0.70, p<0.01, n=26). Principal component analyses, conducted on electrical
      and structural parameters, revealed that the high frequency principal component
      of the dissipation factor was significantly related to SMI (r=0.72, p<0.01,
      n=26). The linear combination of high and low frequency relative permittivity
      predicted 73% of the variation in BV/TV. To conclude, electrical and dielectric
      parameters of trabecular bone, especially relative permittivity and dissipation
      factor, were significantly and specifically related to a trabecular
      microstructure as characterized with microCT. The data gathered in this study
      constitute a useful basis for theoretical and experimental work towards the
      development of impedance spectroscopy techniques for detection of bone quality in
      vitro or in special cases of open surgery.

PMID- 17019040
TI  - Investigation of patient, tumour and treatment variables affecting residual
      motion for respiratory-gated radiotherapy.
AB  - Respiratory gating can reduce the apparent respiratory motion during imaging and
      treatment; however, residual motion within the gating window remains. Respiratory
      training can improve respiratory reproducibility and, therefore, the efficacy of
      respiratory-gated radiotherapy. This study was conducted to determine whether
      residual motion during respiratory gating is affected by patient, tumour or
      treatment characteristics. The specific aims of this study were to: (1) identify
      significant characteristics affecting residual motion, (2) investigate time
      trends of residual motion over a period of days (inter-session) and (3)
      investigate time trends of residual motion within the same day (intra-session).
      Twenty-four lung cancer patients were enrolled in an Institutional Review Board
      (IRB)-approved protocol. For approximately five sessions, 331 four-minute,
      respiratory motion traces were acquired with free breathing, audio instructions
      and audio-visual biofeedback for each patient. The residual motion was quantified
      by the standard deviation of the displacement within the gating window. The
      generalized linear model was used to obtain coefficients for each variable within
      the model and to evaluate the clinical and statistical significance. The
      statistical significance was determined by a p-value<0.05, while effect sizes of
      0.1 cm (one standard deviation) were considered clinically significant. This data
      analysis was applied to patient, tumour and treatment variables. Inter- and intra
      session variations were also investigated. The only variable that was significant
      for both inhale- and exhale-based gating was disease type. In addition, visual
      training displacement, breathing type and Karnofsky performance status (KPS)
      values were significant for inhale-based gating, and dose-per-fraction was
      significant for exhale-based gating. Temporal respiratory variations within and
      between sessions were observed for individual patients. However inter- and intra
      session analyses did not show significant time trends on average for any of the
      variables considered. The lack of significant time trends within and between
      sessions indicates that on average (1) there is no significant learning period
      for breathing training, (2) the patients did not experience training-related
      fatigue and (3) the margin component to account for residual motion during gated
      radiotherapy appears to remain constant throughout the treatment.

PMID- 17019041
TI  - Dosimetric effects of patient rotational setup errors on prostate IMRT
      treatments.
AB  - The purpose of this work is to determine dose delivery errors that could result
      from systematic rotational setup errors (DeltaPhi) for prostate cancer patients
      treated with three-phase sequential boost IMRT. In order to implement this,
      different rotational setup errors around three Cartesian axes were simulated for
      five prostate patients and dosimetric indices, such as dose-volume histogram
      (DVH), tumour control probability (TCP), normal tissue complication probability
      (NTCP) and equivalent uniform dose (EUD), were employed to evaluate the
      corresponding dosimetric influences. Rotational setup errors were simulated by
      adjusting the gantry, collimator and horizontal couch angles of treatment beams
      and the dosimetric effects were evaluated by recomputing the dose distributions
      in the treatment planning system. Our results indicated that, for prostate cancer
      treatment with the three-phase sequential boost IMRT technique, the rotational
      setup errors do not have significant dosimetric impacts on the cumulative plan.
      Even in the worst-case scenario with DeltaPhi=3 degrees, the prostate EUD varied
      within 1.5% and TCP decreased about 1%. For seminal vesicle, slightly larger
      influences were observed. However, EUD and TCP changes were still within 2%. The
      influence on sensitive structures, such as rectum and bladder, is also
      negligible. This study demonstrates that the rotational setup error degrades the
      dosimetric coverage of target volume in prostate cancer treatment to a certain
      degree. However, the degradation was not significant for the three-phase
      sequential boost prostate IMRT technique and for the margin sizes used in our
      institution.

PMID- 17019042
TI  - Quantitative ultrasound imaging detects degenerative changes in articular
      cartilage surface and subchondral bone.
AB  - Previous studies have suggested that quantitative ultrasound imaging could
      sensitively diagnose degeneration of the articular surface and changes in the
      subchondral bone during the development of osteoarthrosis (OA). We have recently
      introduced a new parameter, ultrasound roughness index (URI), for the
      quantification of cartilage surface roughness, and successfully tested it with
      normal and experimentally degraded articular surfaces. In this in vitro study,
      the applicability of URI was tested in bovine cartilage samples with
      spontaneously developed tissue degeneration. Simultaneously, we studied the
      sensitivity of quantitative ultrasound imaging to detect degenerative changes in
      the cartilage-bone interface. For reference, histological degenerative grade of
      the cartilage samples was determined. Mechanical reference measurements were also
      conducted. Cartilage surface roughness (URI) was significantly (p<0.05) higher in
      histologically degenerated samples with inferior mechanical properties.
      Ultrasound reflection at the cartilage-bone interface was also significantly
      (p<0.05) increased in degenerated samples. Furthermore, it was quantitatively
      confirmed that ultrasound attenuation in the overlying cartilage significantly
      affects the measured ultrasound reflection values from the cartilage-bone
      interface. To conclude, the combined ultrasound measurement of the cartilage
      surface roughness and ultrasound reflection at the cartilage-bone interface
      complement each other, and may together enable more sensitive and quantitative
      diagnosis of early OA or follow up after surgical cartilage repair.

PMID- 17019043
TI  - Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and
      stress myocardial blood flows.
AB  - Quantification of myocardial blood flows at rest and stress using 13N-ammonia PET
      is an established method; however, current techniques require a waiting period of
      about 1 h between scans. The objective of this study was to test a rapid dual
      injection single-scan approach, where 13N-ammonia injections are administered 10
      min apart during rest and adenosine stress. Dynamic PET data were acquired in six
      human subjects using imaging protocols that provided separate single-injection
      scans as gold standards. Rest and stress data were combined to emulate rapid dual
      injection data so that the underlying activity from each injection was known
      exactly. Regional blood flow estimates were computed from the dual-injection data
      using two methods: background subtraction and combined modelling. The rapid dual
      injection approach provided blood flow estimates very similar to the conventional
      single-injection standards. Rest blood flow estimates were affected very little
      by the dual-injection approach, and stress estimates correlated strongly with
      separate single-injection values (r=0.998, mean absolute difference=0.06 ml min-1
      g-1). An actual rapid dual-injection scan was successfully acquired in one
      subject and further demonstrates feasibility of the method. This study with a
      limited dataset demonstrates that blood flow quantification can be obtained in
      only 20 min by the rapid dual-injection approach with accuracy similar to that of
      conventional separate rest and stress scans. The rapid dual-injection approach
      merits further development and additional evaluation for potential clinical use.

PMID- 17019044
TI  - Assessing the quality of conformal treatment planning: a new tool for
      quantitative comparison.
AB  - We develop a novel radiotherapy plan comparison index, critical organ scoring
      index (COSI), which is a measure of both target coverage and critical organ
      overdose. COSI is defined as COSI=1-(V(OAR)>tol/TC), where V(OAR)>tol is the
      fraction of volume of organ at risk receiving more than tolerance dose, and TC is
      the target coverage, VT,PI/VT, where VT,PI is the target volume receiving at a
      least prescription dose and VT is the total target volume. COSI approaches unity
      when the critical structure is completely spared and the target coverage is
      unity. We propose a two-dimensional, graphical representation of COSI versus
      conformity index (CI), where CI is a measure of a normal tissue overdose. We show
      that this 2D representation is a reliable, visual quantitative tool for
      evaluating competing plans. We generate COSI-CI plots for three sites: head and
      neck, cavernous sinus, and pancreas, and evaluate competing non-coplanar 3D and
      IMRT treatment plans. For all three sites this novel 2D representation assisted
      the physician in choosing the optimal plan, both in terms of target coverage and
      in terms of critical organ sparing. We verified each choice by analysing
      individual DVHs and isodose lines. Comparing our results to the widely used
      conformation number, we found that in all cases where there were discrepancies in
      the choice of the best treatment plan, the COSI-CI choice was considered the
      correct one, in several cases indicating that a non-coplanar 3D plan was superior
      to the IMRT plans. The choice of plan was quick, simple and accurate using the
      new graphical representation.

PMID- 17019045
TI  - A theoretical investigation into post-operative, intracavitary beta therapy of
      high-grade glioblastomas using yttrium-90.
AB  - Beta therapy with yttrium-90 (90Y) has recently been introduced as a post
      operative intra-cavitary treatment for malignant glioblastoma, a generally
      radioresistant tumour for which cure rates with conventional radiotherapy are
      usually very disappointing. This short theoretical study investigates the
      conditions under which 90Y treatment might be most effective and assesses the
      likely amounts of activity which must be infused in order to successfully cope
      with the low radiosensitivities which characterize such tumours. The
      radiobiological and physical analysis is investigated using the linear quadratic
      (LQ) model and a range of possible scenarios for the distribution and density of
      the tumour cells surrounding the surgically formed cavities are considered. The
      results suggest that, in the absence of diffusion of 90Y from the cavity, the
      activity typically required for 50% tumour cure is well over 40 mCi (1480 MBq),
      this being considerably more than the clinically determined activities which may
      be tolerated. Suggestions are provided for improving the versatility of the
      model.

PMID- 17019046
TI  - Inducible and transmissible genetic events and pediatric tumors of the nervous
      system.
AB  - Tumors of the nervous system most often occur in both children and adults as
      sporadic events with no family history of the disease, but they are also among
      the clinical manifestations of a significant number of familial cancer syndromes,
      including familial retinoblastoma, neurofibromatosis 1 and 2, tuberous sclerosis,
      and Cowden, Turcot, Li-Fraumeni and nevoid basal cell carcinoma (Gorlin)
      syndromes. All of these syndromes involve transmissible genetic risk resulting
      from loss of a functional allele, or inheritance of a structurally defective
      allele, of a specific gene. These genes include RB1, NF1, NF2, TSC1, TSC2, TP53,
      PTEN, APC, hMLH1, hPSM2, and PTCH, most of which function as tumor suppressor
      genes. The same genes are also observed in mutated and inactive forms, or are
      deleted, in tumor cells in sporadic cases of the same tumors. The nature of the
      mutational events that give rise to these inactivated alleles suggests a possible
      role of environmental mutagens in their causation. However, only external
      ionizing radiation at high doses is clearly established as an environmental cause
      of brain, nerve and meningeal tumors in humans. Transplacental carcinogenesis
      studies in rodents and other species emphasize the extraordinary susceptibility
      of the developing mammalian nervous system to carcinogenesis, but the inverse
      relationship of latency to dose suggests that low transplacental exposures to
      genotoxicants are more likely to result in brain tumors late in life, rather than
      in childhood. While not all neurogenic tumor-related genes in humans have similar
      effects in experimental rodents, genetically engineered mice (GEM) increasingly
      provide useful insights into the combined effects of multiple tumor suppressor
      genes and of gene-environment interactions in the genesis of brain tumors,
      especially pediatric brain tumors such as medulloblastoma.

PMID- 17019047
TI  - Heritable susceptibility factors for the development of cancer.
AB  - High frequencies of inherited DNA sequence variations (polymorphisms) are found
      in the human population. The involvement of polymorphic genes (especially for
      chemical metabolism and DNA repair) in the development of cancer is under
      intensive investigation. In our studies, we have irradiated blood lymphocytes
      from normal non-smokers with gamma-rays or UV-light to investigate genotypes and
      DNA repair functions. We found that XRCC1 399Gln and XRCC3 241Met were deficient
      in the repair of gamma-ray-but not UV-light-induced DNA damage that led to the
      expression of chromosome aberrations; therefore the variant genotypes are
      defective in base excision repair. The reverse was found with XPD 312Asn and XPD
      751Gln; therefore they are defective in nucleotide excision repair. XRCC1 194Trp,
      OGG1 326Cys and APE1 148Glu had no DNA repair deficiency based on our
      experimental conditions. In another study, we investigated the role of some of
      these genes on the development of lung cancer. We found a significant increase of
      chromosome aberrations in patients and controls that had the XPD 751Gln and GSTM1
      null genotypes, indicating a mechanistic causation of the disease. Therefore,
      inheritance of susceptibility genes can have significant impact on disease burden
      in the population. On the other hand, there are many questions that need to be
      addressed in order to evaluate the impact of susceptibility on cancer. These
      questions include the understanding of combinations of different polymorphic
      genes for susceptibility and of specific disease susceptibility for different
      ethnic populations.

PMID- 17019048
TI  - Transgenerational transmission of radiation damage: genomic instability and
      congenital malformation.
AB  - The congenital malformation gastroschisis has a genetic disposition in the inbred
      mouse strain HLG/Zte. It is increased after preconceptional irradiation of males
      or females. Radiation exposures during the meiotic stages are most efficient.
      This malformation can also be induced by ionising radiation when the exposure
      takes place during the preimplantation period especially during the zygote stage.
      This latter effect can be transmitted to the next mouse generation. Other
      macroscopically visible or skeletal malformations are not significantly induced
      under these experimental conditions. These latter malformations are increased by
      radiation exposures during major organogenesis. The mechanisms for the
      development of the effects are different. Radiation exposure of the mouse zygote
      (1 to 3 hours p.c.) also leads to the induction of genomic instability in skin
      fibroblasts of the fetus. This phenomenon also occurs in a mouse strain
      (C57BL/6J) which is not susceptible to radiation-induced gastroschisis during the
      preimplantation period. The genomic instability is transmitted to the next mouse
      generation. During genomic instability chromatide breaks are dominating as in non
      exposed cells. With respect to "spontaneous" malformations gastroschisis is
      dominating in HLG/Zte mice. Late radiation effects seem to have similar patterns
      as observed in non-exposed subjects, however, the rates are increased after
      irradiation.

PMID- 17019049
TI  - Radiation induced dynamic mutations and transgenerational effects.
AB  - Many studies have confirmed that radiation can induce genomic instability in
      whole body systems. Although the molecular mechanisms underlying induced genomic
      instability are not known at present, this interesting phenomenon could be the
      manifestation of a cellular fail-safe system in which fidelity of repair and
      replication is down-regulated to tolerate DNA damage. Two features of genomic
      instability namely, delayed mutation and untargeted mutation, require two
      mechanisms of ;damage memory' and ;damage sensing, signal transduction and
      execution' to induce mutations at a non damaged-site. In this report, the
      phenomenon of transgenerational genomic instability and possible mechanisms are
      discussed using mouse data collected in our laboratory as the main bases.

PMID- 17019050
TI  - Germ-line mutations at a mouse ESTR (Pc-3) locus and human microsatellite loci.
AB  - We examined the use of the mouse Pc-3 ESTR (expanded simple tandem repeat) locus
      and 72 human microsatellite loci as potentially sensitive biomarkers for
      mutagenic exposures to germ cells in mice and humans respectively. In the mouse
      work, we treated male mice with TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin; a
      chemical known to induce congenital anomalies in humans and mice) and, analysed
      the F(1) fetuses for Pc-3 mutations. Although the incidence of anomalies was
      higher in the TCDD group, there were no induced mutations. However, respiratory
      distress syndrome (RDS) was observed in 3 of 7 fetuses born to male mice which
      were treated with TCDD and which showed abnormal length of Pc-3 allele. In the
      human studies, the children of Chernobyl liquidators were examined for mutations
      at a total of 72 (31 autosomal, 1 X-linked and 40 Y-linked) microsatellite loci.
      This study was prompted by earlier findings of increases in microsatellite
      mutations in barn swallows and wheat in the highly contaminated areas after the
      Chernobyl accident. We examined 64 liquidator families (70 children) and 66
      control families (70 children). However, no increases in mutation rates were
      found. The estimated mean dose to the liquidators was about 39 mSv and this might
      be one possible reason why no increases of mutations could be found.

PMID- 17019051
TI  - Induced transgenerational genetic effects in rodents and humans.
AB  - Delayed appearance of induced mutations has been observed in Drosophila, plants,
      rodents and recently in humans. The significance of this phenomenon is now
      recognized especially after the pioneering work of Nomura demonstrating
      transgenerational tumour induction in mice following treatment with urethane or
      ionizing radiation. A brief review of the literature on transgenerational genetic
      effects, namely, chromosomal aberrations and mutations, in rodents and humans is
      presented here.

PMID- 17019052
TI  - Delayed manifestation and transmission bias of de novo chromosome mutations:
      their relevance for radiation health effect.
AB  - The origin and transmission of de novo chromosome mutations were reviewed on the
      basis of our chromosome studies in retinoblastoma patients and male infertility.
      In a series of 264 sporadic retinoblastoma families, gross chromosome
      rearrangements involving the RB1 locus were identified in 23 cases (8.7%), of
      which 16 were non-mosaic and 7 were mosaic mutations. The newly formed chromosome
      mutations, whether they were non-mosaic or mosaic, had a strong bias towards
      paternally derived chromosome, indicating that they shared a common mechanism
      where a pre-mutational event or instability is carried over to zygote by sperm
      and manifested as gross chromosome mutation at the early stages of development.
      The de novo chromosome mutations are preferentially transmitted through female
      carriers. This transmission bias is consistent with the finding of higher
      frequencies of translocation carriers in infertile men (7.69% versus 0.27% in
      general populations) in whom meiotic progression is severely suppressed, possibly
      through activation of meiotic checkpoints. Such a meiotic surveillance mechanism
      may minimize the spreading of newly-arisen chromosome mutations in populations. A
      quantitative model of meiotic surveillance mechanism is proposed and successfully
      applied to the published data on ;humped' dose-response curves for radiation
      induced spermatogonial reciprocal translocations in several mammalian species.

PMID- 17019053
TI  - Estimation of the genetic risks of exposure to ionizing radiation in humans:
      current status and emerging perspectives.
AB  - The 2001 report of the United Nations Scientific Committee on the Effects of
      Atomic Radiation (UNSCEAR) on ;Hereditary effects of radiation' incorporates two
      important concepts that have emerged from advances in radiation genetics and
      molecular biology: (a) most radiation-induced mutations are DNA deletions, often
      encompassing multiple genes; however, because of structural and functional
      constraints, only a proportion of induced deletions may be compatible with
      viability and hence recoverable in the progeny and (b) viability-compatible DNA
      deletions induced in human germ cells are more likely to cause multi-system
      developmental abnormalities rather than single-gene diseases. The work reported
      in this paper pursues these concepts further: it examines how mechanistic
      insights gained from studies of repair of radiation-induced DNA double-strand
      breaks (DSBs) in mammalian somatic cells and from those on the origin of
      deletions in human genomic disorders can be extended to germ cells the aim being
      the development of a framework to predict regions of the human genome that may be
      susceptible to radiation-induced deletions. A critical analysis of the available
      information permits the hypothesis that in stem cell spermatogonia, most induced
      deletions may arise via the non-homologous end joining (NHEJ) mechanism of DSB
      repair whereas in irradiated oocytes, the main mechanism is likely to be non
      allelic homologous recombination (NAHR) between misaligned region-specific
      segmental duplications that are present in the genome (NAHR is an error-prone
      form of homologous recombination repair). Should this hypothesis turn out to be
      valid, then it is possible to build on the structural and functional aspects of
      genomic knowledge to devise strategies to predict where in the genome deletions
      may be induced by radiation, their extent and their potential phenotypes.

PMID- 17019054
TI  - Genetic effects of radiation in atomic-bomb survivors and their children: past,
      present and future.
AB  - Genetic studies in the offspring of atomic bomb survivors have been conducted
      since 1948 at the Atomic Bomb Casualty Commission and its successor, the
      Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Past studies
      include analysis of birth defects (untoward pregnancy outcome; namely,
      malformation, stillbirth, and perinatal death), chromosome aberrations,
      alterations of plasma and erythrocyte proteins as well as epidemiologic study on
      mortality (any cause) and cancer incidence (the latter study is still ongoing).
      There is, thus far, no indication of genetic effects in the offspring of
      survivors. Recently, the development of molecular biological techniques and human
      genome sequence databases made it possible to analyze DNA from parents and their
      offspring (trio-analysis). In addition, a clinical program is underway to
      establish the frequency of adult-onset multi-factorial diseases (diabetes
      mellitus, high blood pressure, and cardiovascular disease etc) in the offspring.
      The complementary kinds of data that will emerge from this three-pronged approach
      (clinical, epidemiologic, and molecular aspects) promise to shed light on health
      effects in the offspring of radiation-exposed people.

PMID- 17019055
TI  - Age and sex effects on human mutation rates: an old problem with new
      complexities.
AB  - Base substitution mutations are far more common in human males than in females,
      and the frequency increases with paternal age. Both can be accounted for by the
      greater number of pre-meiotic cell divisions in males, especially old ones. In
      contrast, small deletions do not show any important age effect and occur with
      approximately equal frequency in the two sexes. Mutations in most genes include
      both types, and the sex and paternal age effect depends on the proportion of the
      two types. A few traits, of which Apert Syndrome is best understood, are mutation
      hot spots with all the mutations occurring in one or two codons, usually at one
      nucleotide. They occur with very high frequency almost exclusively in males and
      the frequency increases rapidly with paternal age. It has been suggested that the
      mutant cells have a selective advantage in the male germ-line prior to meiosis.
      Evidence for this surprising, but important, hypothesis is discussed. A possible
      mechanism is the conversion of asymmetrical stem-cell divisions into symmetric
      ones. Some traits with complex etiology show a slight paternal age effect. There
      is also a short discussion of the high deleterious mutation rate and the role of
      sexual reproduction in reducing the consequent mutation load.

PMID- 17019056
TI  - Transgenerational effects of radiation and chemicals in mice and humans.
AB  - Parental exposure of mice to radiation and chemicals causes a variety of adverse
      effects (e.g., tumors, congenital malformations and embryonic deaths) in the
      progeny and the tumor-susceptibility phenotype is transmissible beyond the first
      post-radiation generation. The induced rates of tumors were 100-fold higher than
      those known for mouse specific locus mutations. There were clear strain
      differences in the types of naturally-occurring and induced tumors and most of
      the latter were malignant. Another important finding was that germ-line exposure
      elicited very weak tumorigenic responses, but caused persistent hypersensitivity
      in the offspring for the subsequent development of cancer by the postnatal
      environment. Activations of oncogenes, ras, mos, abl, etc. and mutations in tumor
      suppressor genes such as p53 were also detected in specific tumors in cancer
      prone descendants. However, the majority of tumors observed in the progeny were
      those commonly observed in the strains that were used and oncogene activations
      were rarely observed in these tumors. It can be hypothesized that genetic
      instability modifies tumor occurrence in a transgenerational manner, but so far
      no links could be established between chromosomal and molecular changes and
      transmissible tumor risks. Our data are consistent with the hypothesis that
      cumulative changes in many normal but cancer-related genes affecting
      immunological, biochemical and physiological functions may slightly elevate the
      incidence of tumors or fasten the tumor development. This hypothesis is supported
      by our GeneChip analyses which showed suppression and/or over-expression of many
      such genes in the offspring of mice exposed to radiation. In humans, a higher
      risk of leukemia and birth defects has been reported in the children of fathers
      who had been exposed to radionuclides in the nuclear reprocessing plants and to
      diagnostic radiation. These findings have not been supported in the children of
      atomic bomb survivors in Hiroshima and Nagasaki, who were exposed to higher doses
      of atomic radiation. However, it will be important to follow the human subjects,
      especially for adult type cancers and chronic diseases throughout their lives to
      determine whether the mouse studies can predict human responses.

PMID- 17019057
TI  - Clinical oral doses of dexamethasone decreases intrinsic clearance of quinidine,
      a cytochrome P450 3A substrate in dogs.
AB  - We investigated the effect of dexamethasone (DEX) at clinical doses on the
      pharmacokinetics of quinidine (QN) in dogs. Dogs (5 healthy 1-year-old male
      beagles) were orally administered DEX once daily for 5 days at 2.5 or 7.5 mg/day.
      QN (2 mg/kg) was intravenously injected 3 weeks before and one day after the DEX
      treatment. The plasma concentration of QN was determined by high-performance
      liquid chromatography with fluorometric detection. Plasma concentrations of
      albumin and alpha(1)-acid glycoprotein (AGP) were determined by a bromocresol
      green method and a single immunodiffusion method, respectively. In order to
      calculate unbound concentrations of QN in plasma, the binding kinetics of QN in
      plasma was examined by an ultrafiltration method using pooled plasma from the 5
      dogs when they were drug-free. Total body clearance of QN was decreased dose
      dependently By the DEX treatment, although the decrease was not statistically
      significant. Elimination half-lives significantly increased (more than twice at
      7.5 mg), and intrinsic clearance significantly decreased (about 50%). The volume
      of distribution increased significantly (about two-fold). Plasma levels of AGP
      significantly decreased, and the unbound fraction of QN in plasma significantly
      increased. Our results demonstrate that clinical doses of DEX significantly
      affect the pharmacokinetics of QN, a CYP3A substrate in dogs, by decreasing CYP3A
      activity and plasma AGP levels. There is a possibility that adverse drug-drug
      interaction occurs during DEX therapy through its effects on CYP3A activity and
      plasma AGP levels.

PMID- 17019058
TI  - Gross morphological features of the lung and air sac in the Japanese quail.
AB  - This study was conducted to reveal the morphological characteristics of the lung
      and air sacs in Coturnix coturnix japonica (Japanese quails). Ten quails were
      allocated into two groups. Tracheas of 5 quails with neoprene latex and 5 quails
      with methylmetacrylate were injected to fill the trachea and air sacs. Latex
      embalmed animals were stored in 10% formaldehyde solution for two months. Animals
      given methylmetacrylate were maserated in 30% potassium hydroxide at 40 degrees C
      for two days. Lungs were located in the dorsal part of the thorax and very close
      to the thoracic vertebrae and ribs. Shorter than the dorsal border, the ventral
      border lied between the 3rd and 6th ribs. Cervical, clavicular, cranial thoracic,
      caudal thoracic and abdominal sacs were identified. These sacs had connection
      with the 3rd, 4th and 5th lateroventral and 4th mediolateral bronchi. Saccus
      cervicalis was located on the left and right portions of the vertebrae cervicales
      et thoraricae with a pronounced communication ventromedially. However, the
      cervical sac aeration of only all cervical vertebrae was present in this study.
      Humerus was a non-aerated bone. Pneumatic foramen was absent and did not aerate
      the sternum. Cranial thoracic sac connected to the 1st, 2nd and 4th medioventral
      bronchi and gave no diverticulum for aeration. Cranial thoracic sac received air
      through the 4th medioventral and the 1st and 2nd lateroventral bronchi. Left and
      right abdominal air sacs paramedially produced diverticulum femorale, but this
      diverticulum did not enter the femur.

PMID- 17019059
TI  - Distribution of cortical bone in bovine limbs.
AB  - Xenogenic bone grafts have been widely researched because they are not limited in
      terms of volume and size like autogenous and allogenic grafts, and the favored
      bone for xenografts is bovine bone. However, the efficacy of cortical bone from
      bovine limb for xenografts is not clearly known. In this study, the distribution
      of cortical bone in bovine humerus, radius, femur, and tibia were investigated.
      Each experimental bone was split longitudinally with a bone saw and bone marrow
      and cancellous bone were removed. The thicknesses of cortical layers in sample
      diaphyses were measured at 1cm intervals using a micrometer. The mean lengths of
      cortical portions were; humerus 14.7 +/- 2.3 cm, radius 19.0 +/- 2.6 cm, femur
      19.0 +/- 3.2 cm, and tibia 23.0 +/- 3.1 cm. Thickest cortical bone was found at
      the distal caudal metaphysis of the humerus, the proximal caudal metaphysis of
      the radius, the craniolateral and caudomedial midshaft of the femur and the
      lateral and medial midshaft of tibia. The mean surface areas of cortical bone
      were humerus 187.4 +/- 15.44 cm2, radius 229.2 +/- 43.31 cm2, femur 295.8 +/-
      8.93 cm2, and tibia 290.0 +/- 30.44 cm2. And, mean volumes of cortical bone were
      humerus 149.42 +/- 15.35 cm3, radius 166.26 +/- 20.02 cm3, in femur 220.45 +/-
      22.73 cm3, and tibia 214.89 +/- 20.05 cm3. The results of this study can be used
      to produce cortical bone-based plates and screws.

PMID- 17019060
TI  - Efficacy of oseltamivir phosphate to horses inoculated with equine influenza A
      virus.
AB  - We investigated the efficacy of the oral administration of oseltamivir phosphate
      (OP) in horses experimentally infected with equine influenza A virus (H3N8). Nine
      horses were divided into three horses each of control, treatment and prophylaxis
      groups. An administration protocol for the treatment group (2 mg/kg of body
      weight, twice a day for five days) was started immediately after the onset of
      pyrexia (above 38.9 degrees C). An administration protocol for the prophylaxis
      group (2 mg/kg of body weight, once a day for five days) was started on a day
      before viral inoculation. In the treatment group, periods of virus excretion
      (mean days +/- standard deviation, 2.3 +/- 0.6) and pyrexia (2.0 +/- 0.0) were
      apparently shorter than those of the control group (6.0 +/- 0.0 and 8.0 +/- 1.0,
      respectively). In the prophylaxis group, although virus excretion and pyrexia
      were not prevented, the periods of virus excretion (5.0 +/- 0.0) and pyrexia (4.7
      +/- 1.5) were shorter than those of the control group. Moreover, in the treatment
      and prophylaxis groups, bacterial counts of Streptococcus equi subsp.
      zooepidemicus known as the common pathogen of secondary bacterial pneumonia in
      bronchoalveolar lavage fluids collected seven days after inoculation were
      significantly fewer than that of the control group. The results indicated that
      the oral administration of OP to horses affected with equine influenza would
      contribute to reduce the magnitude of virus excretion, pyrexia and consequent
      secondary bacterial pneumonia.

PMID- 17019061
TI  - Prognostic factors associated with survival in dogs with lymphocytic-plasmacytic
      enteritis.
AB  - Prognostic factors associated with survival in dogs with lymphocytic-plasmacytic
      enteritis (LPE) were investigated through a retrospective study. Using case
      records, 48 dogs diagnosed with LPE were classified as survivors (n = 32) or non
      survivors (n = 16), and the clinical and clinicopathological parameters were
      reviewed between the 2 groups by using univariate and multivariate prognostic
      analysis. Compared to the hospital population, non-survivors had an
      overrepresentation of the Shiba breed. Results of univariate analysis indicated
      that anorexia, severe weight loss, packed cell volume, and total protein were
      significantly associated with survival for 6 months after diagnosis. In
      multivariate analysis, anorexia and hypoproteinemia were significantly associated
      with survival. Furthermore, initial response to treatment was strongly associated
      with poor prognosis. Based on these clinical and laboratory parameters such as
      anorexia, hypoproteinemia and initial response to treatment, it may be possible
      to predict poor prognosis in canine LPE.

PMID- 17019062
TI  - Evaluation by weight change rate of dairy herd condition.
AB  - The purpose of this study was to clarify whether weight change rate (WCR) is
      useful in evaluating herd health. Five herds (A, B, C, D, and E) were examined
      monthly for approximately 1 year to measure both WCR and BCS. WCR was calculated
      using the following equation: WCR (%) = (body weight of current month-body weight
      of the preceding month)/body weight of current month x 100. In addition, blood
      profiles were performed in each herd before and after calving. The incidence of
      periparturient diseases was higher in Herds A, B, and C compared with Herds D and
      E. Reproductive performance in Herds A and B was rather poor compared with Herds
      C, D, and E. There were significantly lower WCRs in Herd A compared with Herd C
      during the period of day -30 to day 30 after calving. According to the blood
      profiles, high levels of non-essential fatty acids (NEFA) were observed during
      the period of day -30 to -1 and high beta-hidroxybutyricacid (BHB) and low levels
      of glucose were observed at day 30 after calving in Herd A. A marked poor
      condition in Herd A during the peripaturient period was clearly expressed by low
      WCR in this experiment. WCR can express body condition of herds and is suggested
      to be a useful parameter in the determination of herd performance in field
      experiments.

PMID- 17019063
TI  - Complete cDNA sequences and phylogenetic analyses of the Th1 and Th2 cytokines of
      the bactrian camel (Camelus bactrianus).
AB  - The complementary DNAs of the Th1 (IL-2, IL-12p35, and IFN-gamma) and Th2 (IL-4,
      IL-10 and IL-13) cytokine genes of the bactrian camel (Camelus bactrianus) were
      cloned, sequenced, and analyzed. IL-2, IL-4, IL-10, IL-12p35, IL-13, and IFN
      gamma were found to have 465, 402, 537, 669, 411, and 501 bp length open reading
      frames with 154, 133, 178, 222, 136, and 166 amino acid encodings, respectively.
      The homology ranged from 58.8% to 100% between the nucleotide sequences of the
      camel cytokine genes and the published sequences of other mammalian genes,
      including the llama, pig, cow, horse, human, and mouse. The cDNA had highest
      homology with orders Artiodactyla (pigs and cattle) and Perissodactyla (horses),
      especially to the recently cloned llama sequences.

PMID- 17019064
TI  - The effects of growth and disease in serum keratan sulfate concentration in dogs.
AB  - The purpose of this study is to investigate keratan sulfate (KS) concentration in
      the serum of puppies and the effects of age, body weight, breed and diseases.
      Serum samples from six neonatal dogs (4 Beagles, 2 Labrador Retrievers), and from
      127 adult dogs with various diseases were collected at a Teaching Animal
      Hospital. Canine serum KS concentration was measured by inhibition enzyme-linked
      immunosorbent assay (ELISA). Samples from puppies were evaluated for growth
      related changes, and samples from patients were evaluated for age, body weight,
      breed and disease-related changes. Serum KS concentration was high in puppies
      from birth to 4 months of age. KS values started to decrease from 4 months to 9
      months of age, and then gradually reached to the plateau. Though in the small
      sample, mean KS concentration in a Labrador Retriever was higher than in Beagles
      during the first 10 months. The values of serum KS showed body weight-related
      increase within retrievers among teaching hospital population and there was
      significant increase in body weight-related change. Cartilage metabolism is high
      in canine immature joint and that activity continues for 5 months, and that
      higher in Labrador Retrievers rather than in Beagles. There was no effect from
      other factors, including age, body weight, breed and disease in all patients.
      Serum KS concentration of Retrievers is higher than Beagles, and that value
      increased with gain of body weight. We suggest that Retriever have higher
      cartilage metabolism with growth or ageing.

PMID- 17019065
TI  - Structure of bovine fungiform taste buds and their immunoreactivity for
      gustducin.
AB  - The taste buds of bovine fungiform papillae were studied by light and electron
      microscopy using both histological and immunohistochemical methods. The taste
      buds existed in the epithelium of the apical region of the papillae. By electron
      microscopy, two types of taste cells, namely type I and type II cells, could be
      classified according to the presence of dense-cored vesicles, the cytoplasmic
      density and the cell shape. Type I cells were thin, had an electron-dense
      cytoplasm containing dense-cored vesicles, and possessed long thick apical
      processes in the taste pore. Type II cells were thick, had an electron-lucent
      cytoplasm containing many electron-lucent vesicles, rather than dense-cored
      vesicles, and possessed microvilli in the taste pore. Immunohistochemical
      staining with an antiserum against gustducin was investigated by both light and
      electron microscopy using the avidin-biotin complex (ABC) method. Some, but not
      all, of the type II cells exhibited gustducin immunoreactivity, whereas none of
      the type I cells showed any immunoreactivity.

PMID- 17019066
TI  - Involvement of neuropeptide Y in hyperphagia in human growth hormone transgenic
      rats.
AB  - We have previously produced human growth hormone (hGH) transgenic (TG) rats that
      show low circulating levels of both hGH and endogenous rat GH. Although body
      length of the TG rats is normal, they develop hyperphagia and severe obesity. The
      present study was undertaken to elucidate the causes of hyperphagia in the TG
      rats by focusing on temporal changes in plasma ghrelin levels and hypothalamic
      neuropeptide Y (NPY) contents. In both wild-type (WT) and TG rats, the highest
      value of plasma ghrelin levels was observed just before the dark phase, and
      thereafter plasma ghrelin levels were maintained higher in the TG than WT rats.
      Although NPY contents also showed the peak level just before the dark phase in
      both the arcuate (ARC) and paraventricular nuclei (PVN) of the hypothalamus, the
      values in the ARC, but not the PVN, of the TG rats was always lower than those of
      the WT rats, suggesting increased transport of NPY from the ARC to PVN in the TG
      rats. In addition, treatment with antagonists for Y1 and Y5 receptors for NPY
      reduced food intake much more effectively in the TG than WT rats. Intermittent
      treatment with recombinant hGH for a week significantly decreased food
      consumption, adipose tissue weight and plasma triglyceride concentrations in the
      TG rats. These results suggest that, in the TG rats, insufficiency in circulating
      GH stimulates the ghrelin-NPY system with a resultant increase in food intake.

PMID- 17019067
TI  - Hemodynamic characteristics of vasopressin in dogs with severe hemorrhagic shock.
AB  - The effect of vasopressin was compared with that of the established vasopressor
      epinephrine in experimentally induced hemorrhagic shock. After rapid crystalloid
      resuscitation in a ratio of three volumes of 0.9% saline to one volume of blood
      (3:1 crystalloid resuscitation), six dogs were given 0.4 IU/kg vasopressin and
      another six dogs were given 0.1 mg/kg epinephrine. Five dogs in the control group
      were given fluid resuscitation in the same manner as above without administration
      of any drugs. Administration of vasopressin increased diastolic arterial pressure
      (DAP) from 45.0 +/- 4.9 to 91.2 +/- 9.6 mmHg within 5 min, compared with
      epinephrine from 46 +/- 4.0 to 51.8 +/- 7.7, and control from 47.3 +/- 7.5 to
      46.3 +/- 7.3. Systolic arterial pressure (SAP) did not increase significantly
      following vasopressin compared with epinephrine and control group. Results of DAP
      and systemic vascular resistance index (SVRI) suggested that vasopressin
      administration was vasoconstrictive after fluid resuscitation in decompensatory
      hemorrhagic shock in dogs, whereas epinephrine did not compared with control. In
      addition, epinephrine did not affect the cardiac index (CI) and SVRI, while a
      significant decrease in CI and increase in SVRI were observed in vasopressin
      group. The pressor effect of epinephrine in the vascular system was abrupt and
      only lasted a short period of time (within 5 min), while that of vasopressin was
      steady and lasted for more than 1 hr, especially regard to in DAP. When compared
      with epinephrine, vasopressin can be a more effective and safer choice in
      patients with severe hemorrhagic shock.

PMID- 17019068
TI  - Fecal D- and L- lactate, succinate, and volatile fatty acid levels in young dairy
      calves.
AB  - For evaluation of physiologically significant organic anions in the colonic
      environment, 87 samples of normal feces were collected from the rectum of 15
      calves less than 60 days old. The calves were fed milk replacer with free access
      to starter diet and hay. After fecal extraction with water, pH, D- and L-lactate,
      succinate, and volatile fatty acid (VFA) concentrations were determined. There
      was wide variation in fecal pH (4.3 to 7.7). Higher lactate concentrations were
      observed in feces samples with lower pH, and most of these samples were collected
      during the first 4 weeks of life. Elevated lactate concentrations included both
      the D- and L-isomers, and the D-isomer comprised approximately 30-50% of total
      lactate. Elevated succinate concentrations were observed in only 8 fecal samples,
      while other samples had lower or trace amounts of succinate. Elevated fecal
      succinate showed no relationship with fecal pH or VFA concentrations. Fecal VFA
      concentrations were lower in samples collected in the early postnatal stage, but
      fecal VFA concentrations were not necessarily related to age. We confirmed that
      fecal D- and L-lactate concentrations increased with a concomitant decrease of
      VFA in the acidic lumen of the colon, although acidic feces were not necessarily
      accompanied by elevated concentrations of lactate. In contrast, succinate
      production was not related to fecal pH or VFA concentrations.

PMID- 17019069
TI  - Canine ovarian serous papillary adenocarcinoma with neoplastic hypercalcemia.
AB  - A female golden retriever was referred to assess a history of a palpable
      abdominal mass. A serum chemistry analysis revealed elevated concentrations of
      blood urea nitrogen, creatinine, calcium, and parathyroid hormone-related protein
      (PTH-rP). Exploratory laparotomy revealed an ovoid mass within the right ovary.
      This mass was removed surgically by performing an ovariohysterectomy. The right
      ovarian mass was diagnosed as a serous papillary adenocarcinoma. Following
      surgery, the dog recovered, and the serum calcium and PTH-rP concentrations
      decreased. Therefore, concentrations of PTH-rP and calcium might be associated
      with serous papillary adenocarcinomas. Serial evaluation of the serum PTH-rP and
      calcium was useful for evaluating the prognosis.

PMID- 17019070
TI  - Synovial sarcoma of the tendon and tendon sheath in a dog.
AB  - A 19.5-year-old male mongrel dog developed a progressive lameness and swelling
      around the right carpus. A tumor (6 x 3 x 3 cm) was found in the caudal of distal
      antebrachium of the right forelimb, including tendons of the superficial digital
      flexor muscle and deep digital flexor muscle. No joint destruction was observed.
      The tumor consisted of round and spindle cells arranged in a compact sheet. There
      were occasional slit-like spaces or lumina, and areas rich in collagen fibers
      giving an appearance of tendon tissues. Neoplastic cells gave a positive
      immunoreaction to vimentin, but negative reactions to antibodies against S-100
      protein, cytokeratin and myoglobin. Based on these findings, this tumor was
      diagnosed as a synovial sarcoma generating from the tendon and tendon sheath,
      which is very uncommon in dogs.

PMID- 17019071
TI  - A trial of intrauterine insemination using a fiberscope in the giant panda
      (Ailuropoda melanoleuca).
AB  - An intrauterine insemination technique using a fiberscope was investigated in the
      giant panda. A septal wall was present about 5 cm from the vulva, the external
      urethral orifice was present in the ventral region, and the entrance
      (pseudocervix) to the vagina was present in the dorsal region. The uterovaginal
      region protruded in the dorsal region about 15 cm from the pseudocervix. The
      external uterine orifice was present in the uterovaginal region, revealing that
      intrauterine insemination can be easily performed. This technique may greatly
      contribute to artificial reproduction of the giant panda.

PMID- 17019072
TI  - Two Eimeria species isolated from wild Japanese rock ptarmigans (Lagopus mutus
      japonicus) in Japan.
AB  - Fecal samples were collected from 64 Japanese rock ptarmigans (Lagopus mutus
      japonicus) at 13 locations in the alpine zone of Japan and examined for internal
      parasites. We found 2 morphologically different types of eimerian oocysts. Based
      on morphological characteristics, one was identified as Eimeria uekii, which had
      already been found from Japanese rock ptarmigans in 1981, and the other was
      likely a new type of Eimeria. The new type of eimerian oocysts required a longer
      sporulation time than E. uekii. The prevalence of both eimerian oocysts in
      Japanese rock ptarmigans was 62.5%, while that of E. uekii was 60.9% and the new
      type 29.7%. Mixed infection of both types was found in 28.1%.

PMID- 17019073
TI  - Radiographic evaluation of caudal vena cava size as a useful parameter for the
      diagnosis of heart disease in dairy cattle.
AB  - To quantify the radiographic parameters of the caudal vena cava (CVC) in healthy
      cattle and demonstrate their clinical usefulness, the present study compared the
      ratios of the diameter of the thoracic CVC to the diameter of the aorta (Ao) and
      length of the thoracic vertebrae (VL), which are all positioned in the same
      intercostal space, in 81 healthy control cattle (43 growing, 38 adult) and 10
      cattle with heart disease. The average diameter of the CVC (CVCave) was
      correlated with the size of the Ao and VL in the control cows. Although the
      diameter and pulsation index of the CVC differed significantly between the
      growing and adult cows, the ratios of CVC/Ao and CVC/VL were fixed values for
      both the growing and mature cattle. However, in the cattle with heart disease,
      the pulsation index of the CVC was significantly lower or there was absence of
      pulsation due to a dilated CVC, and the ratio of CVCave/Ao and CVCave/VL were
      significantly higher than those in the healthy cattle.

PMID- 17019074
TI  - Immunolocalization of steroidogenic enzymes P450scc, 3betaHSD, and P450c17 in the
      ovaries of wild raccoon dogs (Nyctereutes procyonoides).
AB  - We investigated the distribution of 3 types of steroidogenic enzymes, P450scc,
      3betaHSD, and P450c17, in wild raccoon dog ovaries by immunohistochemistry. Six
      pairs of ovaries were obtained from wild raccoon dogs between 2001 and 2003, with
      3 of the 6 pairs of ovaries containing corpora lutea. P450scc, 3betaHSD, and
      P450c17 were localized in the granulosa and theca cells of these raccoon dogs.
      Furthermore, lutein cells were stained positively for P450scc and 3betaHSD in the
      pregnant and non-pregnant raccoon dogs. These results suggest that granulosa and
      theca cells may synthesize progesterone and androgens, which may play an
      important role in follicular development, and that lutein cells are a major
      source of progesterone in wild raccoon dogs.

PMID- 17019075
TI  - Fibrodysplasia ossificans progressiva-like condition in a cat.
AB  - Fibrodysplasia ossificans progressiva (FOP)-like condition was diagnosed in a
      Japanese domestic cat with stiffness, marked atrophy of the muscles, and limited
      mobility of all joints in both the pelvic limbs. Etretinate, a retinoid, was used
      for medical management; however, no improvement in the clinical signs was
      observed. Inheritance of the disorder has not yet been demonstrated. Furthermore,
      the clinical signs and histopathological findings of feline FOP-like condition in
      the present case differed from those of the previously reported cases.

PMID- 17019076
TI  - Seroepidemiologic survey of Coxiella burnetii and attempt to detect Coxiella DNA
      in aged non-laying chickens in a prefecture of Japan where poultry farming
      prospers.
AB  - The indirect fluorescent antibody test (IFAT) revealed seropositivity to Coxiella
      burnetii in aged non-laying chickens in poultry farms in a prefecture in the
      central part of Japan. Seropositivity was 7%, and antibody titers ranged from 16
      to 64. No DNA fragment specific for C. burnetii was detected in the chickens by
      nested-PCR. The prevalence of C. burnetii infection in a prefecture of Japan in
      which poultry farming prospers was 7%.

PMID- 17019077
TI  - Distribution of carbonic anhydrase in digestive tract of pond loach (Misgurnus
      anguilicaudatus).
AB  - Carbonic anhydrase (CA) family is discovered in various species including
      mammals, avians and even plants, but it is rarely reported in fishes. Ten Pond
      Loaches were used in this study. The results indicated that no evidence of
      distribution of CA in esophagus. Nonetheless CA was found in the mucosal
      epithelium of stomach and in the villous epithelium of intestine demonstrated
      histochemically by the numerous black sedimentation of cobaltous sulfide (CoS) in
      these areas. In addition, black sedimentations of CoS were also found in all the
      vascular endothelium examined and red blood cells of digestive tract. The
      distribution of CA in Pond loach was more closely resemble amphibians than to
      other species, suggesting evolutional adaptation for Pond loach in aquatic
      environments.

PMID- 17019078
TI  - Endocrinological markers for assessment of hyperandrogenemia in hirsute women.
AB  - BACKGROUND: Measured endocrinological parameters (total testosterone [TT], free
      testosterone [FT], dihydrotestosterone [DHT], dehydroepiandrosterone sulfate
      [DHEAS], and sex hormone binding globulin [SHBG]) and calculated parameters
      (calculated FT (cFT), calculated bioavailable testosterone (cBT), and the free
      androgen index [FAI]) in women with hirsutism were compared to the values of a
      control group. The question remains if cFT or cBT are more appropriate markers
      for assessment of hyperandrogenemia in clinical situations such as hirsutism in
      women. METHODS: Sixty-six women showed an modified Ferriman-Gallwey (mF-G) score
      of >or=6 and were classified as hirsutism group and 58 women showed mF-G scores
      of <or=5 and were classified as control group. TT, FT, DHT, DHEAS, and SHBG were
      measured with enzyme immunoassays in one serum sample. Albumin was measured in
      the same sample. Afterwards, cFT, cBT, and the FAI were calculated. RESULTS: The
      hirsutism group revealed significantly increased cFT, cBT, and FAI, while SHBG
      was significantly decreased compared to the controls. All values of the hirsutism
      group showed significant, but poor correlation with the mF-G score. SHBG
      correlated negatively with the mF-G score and BMI. CONCLUSION: Despite the
      limited correlation of all endocrinological parameters to severity of hirsutism
      described by the mF-G score, cFT, cBT, and FAI may be more appropriate markers
      for assessment of hyperandrogenemia in women with hirsutism in comparison with
      measured values of simple enzyme immunoassays.

PMID- 17019079
TI  - Seasonal variation in blood pressure of patients on continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND: A seasonal variation in blood pressure (BP) has been observed in
      hemodialysis and renal transplant patients. However, this phenomenon in
      continuous ambulatory peritoneal dialysis (CAPD) patients, whose hemodynamics are
      different from hemodialysis patients, has not been reported before. In addition,
      the contribution of extracellular water (ECW) in the seasonal variation in BP is
      not clear. METHODS: All stable CAPD patients (n = 122) dialyzed in a single
      center from January 1, 2003 to December 12, 2004 were studied. Systolic blood
      pressure (SBP), diastolic blood pressure (DBP), weight and ECW (by bioimpedance
      analysis) were measured in every patient. Climatic data were obtained from the
      Beijing Weather Bureau. These data were pooled together and grouped according to
      the calendar month. RESULTS: In general, an apparent seasonal variation in BP was
      observed in CAPD patients. BP began to decrease from spring and reached the
      lowest level in summer, then increased from autumn and reached its peak in
      winter. The seasonal variation in BP in male patients was similar to that in
      female patients, but in comparison to non-diabetic patients there was no apparent
      seasonal variation in the BP of diabetic patients. SBP and DBP negatively
      correlated with the average atmospheric temperature (r = -0.768, p < 0.001 and r
      = -0.764, p < 0.001, respectively). BP also negatively correlated with rainfall
      and humidity, but this correlation disappeared when temperature was controlled in
      partial correlation analysis. Weight and ECW fluctuated throughout the year but
      showed no seasonal variation. CONCLUSION: On the whole there was an apparent
      seasonal variation in blood pressure in CAPD patients. As opposed to non-diabetic
      patients, there was no apparent seasonal variation in BP in diabetic patients.
      The seasonal variation in BP was influenced more by temperature than rainfall and
      humidity, and the change in ECW was not seasonal, suggesting that other
      mechanisms such as total peripheral resistance might play a more important role
      in this phenomenon.

PMID- 17019080
TI  - Factors affecting human IgE and IgG responses to allergen-like Schistosoma
      mansoni antigens: Molecular structure and patterns of in vivo exposure.
AB  - BACKGROUND: The human IgE response is associated with allergy and with host
      defence against parasitic worms. A response to Sm22.6, the dominant IgE antigen
      in adult Schistosoma mansoni worms, correlates with resistance to re-infection
      after treatment. Sm22.6 is one of a family of EF-hand containing parasite
      proteins with sequence similarity to dynein light chain (DLC) and with major non
      parasite allergens. Here we compare human IgE and IgG responses to other family
      members, Sm20.8 and Sm21.7, as well as to SmDLC1, relating these to antigen
      structure and expression in parasite life stages. METHODS: Recombinant antigens
      were used in ELISA to measure antibody isotype responses in 177 cases from an
      endemic area, before and 7 weeks after treatment. Parasite antigen expression was
      assessed by RT-PCR and Western blotting. RESULTS: Levels of antibodies to Sm22.6
      and Sm20.8 (but not to Sm21.7 or SmDLC1) showed posttreatment increases in all
      but young children. Many produced IgE to Sm22.6 and Sm20.8 (2 EF-hands), few to
      Sm21.7 (1 EF-hand) or SmDLC1 (no EF-hands). Sm21.7 was expressed in cercariae,
      adults and eggs, Sm22.6 and Sm20.8 were concentrated in the adult. CONCLUSIONS:
      These studies suggest that IgE antigens Sm22.6 and Sm20.8 are only released to
      boost antibodies when adult worms die, whilst Sm21.7 and SmDLC1 are released
      constantly from eggs dying in host tissue. IgE responses to these allergen-like
      molecules may be influenced by patterns of exposure and the number of EF-hand
      motifs.

PMID- 17019082
TI  - Comparison of solutions for sublingual immunotherapy.

PMID- 17019081
TI  - Secondary anetoderma associated with mastocytosis.
AB  - BACKGROUND: Mastocytosis represents a wide spectrum of proliferative disorders of
      mast cells in the bone marrow, skin and/or internal organs. The most common
      manifestation is urticaria pigmentosa (UP), which is characterized by small or
      large brown-red maculopapules on the skin. Occasionally, elastic and collagen
      fibers in the lesions degenerate and result in a lax area of skin termed
      anetoderma. METHODS: We report a 21-year-old male patient with multiple cutaneous
      anetodermic lesions, present since infancy, at UP sites confirmed with
      histochemistry. RESULTS: Urinary N-methyl 24-hour histamine levels were elevated,
      but serum tryptase levels were within normal limits. Radiologic examination of
      long bones was unremarkable, as well as all other blood results. UP biopsy showed
      absence of epidermal involvement and increased number of mast cells located
      perivascularly. There was fragmentation of elastic fibers in the papillary
      dermis. CONCLUSIONS: A patient with multiple cutaneous anetodermic lesions,
      presented since infancy, led to the diagnosis of UP. Such an association is rare
      and raises intriguing questions concerning the pathogenesis of anetoderma.

PMID- 17019083
TI  - Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind,
      randomized, placebo-controlled study to measure the effect of FX06 (a fibrin
      derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with
      acute myocardial infarction undergoing primary percutaneous coronary
      intervention.
AB  - Immediate reopening of acutely occluded coronary arteries via primary
      percutaneous coronary intervention (PCI) is the treatment of choice to salvage
      the ischemic myocardium in the setting of ST-segment elevation myocardial
      infarction (STEMI). However, the sudden re-initiation of blood flow achieved with
      PCI can lead to a local acute inflammatory response with further endothelial and
      myocardial damage. This phenomenon, described as 'reperfusion injury', has been
      recognized for several decades, yet no pharmacologic intervention has so far
      succeeded in reducing myocardial damage linked to reperfusion. FX06 is a
      naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15
      42)). It prevents leukocyte migration through the gap junctions of endothelial
      cells. Experimental studies have shown that FX06 inhibits the binding of the
      proinflammatory fibrin E1 fragment to VE-cadherin expressed in the adherence
      junction. It represents a novel approach to reducing local and systemic
      inflammation, including myocardial reperfusion injury, in the adherens junction.
      The present multicenter, double-blind, randomized, placebo-controlled study is
      designed to test the hypothesis that FX06 injection during and immediately after
      primary PCI can reduce infarct size in patients with STEMI. The primary outcome
      measure of efficacy in this study is the degree of myocardial salvage calculated
      as the difference between the perfusion defect before and after PCI, determined
      by myocardial perfusion scintigraphy during rest. Further, infarct size at the
      end of the index hospitalization, as well as at 4 months, will be measured by
      cardiac magnetic resonance imaging. The present position paper describes the
      rationale, design and the methods utilized in this trial.

PMID- 17019084
TI  - A posterior probability of linkage-based re-analysis of schizophrenia data yields
      evidence of linkage to chromosomes 1 and 17.
AB  - OBJECTIVE: Linkage analysis using 22 Canadian pedigrees identified a promising
      schizophrenia candidate region on 1q23 with a maximum 2-point HLOD under a
      recessive model of 5.8 [Brzustowicz et al. 2000]. In the current study, we
      revisited this data set using a Bayesian linkage analysis technique, namely the
      posterior probability of linkage (PPL). METHODS: The PPL has been developed as an
      alternative to traditional linkage analysis. It differs from both LOD scores and
      'non-parametric' methods in that it directly measures the probability of linkage
      given the data, and incorporates prior genomic information. RESULTS: As expected,
      PPL results for 1q23 supported the previously observed linkage, with an estimated
      multipoint PPL of 99.7%. However, the PPL supported two further results: a second
      peak on chromosome 1 at 1p13 with a multipoint with PPL of 70% and a chromosome
      17 marker (D17S784 at 17q25) with a multipoint PPL of 44%. CONCLUSIONS: The PPL
      based analysis presented has the advantage over other likelihood-based linkage
      methods in that it avoids maximization and produces a less complex view of the
      strength of evidence for linkage.

PMID- 17019085
TI  - Colocutaneous fistula after mesh plug inguinal hernia repair- a delayed
      complication.

PMID- 17019086
TI  - Lipoma of the parietal peritoneum: an unusual cause of abdominal pain.

PMID- 17019087
TI  - Genetic considerations in recurrent congenital diaphragmatic hernia in two
      siblings.

PMID- 17019088
TI  - A congenital cyst of the pancreas.

PMID- 17019089
TI  - Two cases of pulmonary metastasis after living donor liver transplantation for
      hepatocellular carcinoma.

PMID- 17019090
TI  - A 52-year-old woman with a subcutaneous, slightly movable and painless nodule in
      the left breast.

PMID- 17019091
TI  - Laryngeal papillomatosis treated by oral zinc sulphate.

PMID- 17019092
TI  - The pattern of gynecological malignancies in 968 cases from Pakistan.

PMID- 17019093
TI  - Relation of serum adenosine deaminase (ADA) levels with sputum smear conversion
      in patients with pulmonary tuberculosis.

PMID- 17019095
TI  - Chylothorax-complicated chronic lymphocytic leukemia.

PMID- 17019094
TI  - The underuse of analgesia and sedation in pediatric emergency medicine.

PMID- 17019096
TI  - Influence of atopic history on cord blood IgE.

PMID- 17019097
TI  - Lung involvement in inflammatory bowel diseases.

PMID- 17019098
TI  - Repair of pectus deformities: experience and outcome in 317 cases.
AB  - BACKGROUND: The most common congenital chest wall deformities are pectus
      excavatum and pectus carinatum. Various techniques have been described for
      correction of pectus deformities. We describe our experience with surgical repair
      of pectus deformity (PD) in adults, including our new technique, which uses a
      resorbable plaque for fixation of the sternum. METHODS: We reviewed the records
      of 317 patients who underwent surgical correction of PD between October 1997 and
      December 2005. RESULTS: All of the patients were male and the median age was 21.3
      years (range, 16-32 years). Of 317 patients, the type of deformity was a pectus
      excavatum in 230 patients and a pectus carinatum in 87 of the patients. Four
      different operative techniques were used. There were no intraoperative deaths or
      major perioperative morbidity. The complications rate was 17%. Overall mean
      hospital stay was 14.25 days. In 208 patients who underwent a mid-term outpatient
      follow up (mean, 8 months), there was no recurrence. Patient satisfaction was
      excellent in 234 patients, good in 79 patients and fair in 4 patients.
      CONCLUSION: The majority of patients with pectus deformity had been operated on
      during childhood; therefore there is limited published information about the
      correction of pectus excavatum and pectus carinatum deformities in adults. The
      most important point in pectus correction is to achieve proper and long-term
      stability of the sternum following osteotomy. Various techniques can be used for
      this purpose.

PMID- 17019099
TI  - Circulating levels of endothelin-1 in a homogenous Gulf Arab population with
      untreated essential hypertension.
AB  - BACKGROUND: Racial variations are reported in the natural history of
      hypertension. For example, hypertension is significantly more prevalent in blacks
      than whites. Endothelial cells are important regulators of vascular tone and
      homeostasis, in part through secretions of vasoactive substances including
      endothelin-1 (ET-1), a small peptide with potent vasopressor actions. In black
      hypertensives, ET-1 levels are higher than in normotensive blacks and in both
      hypertensive and normotensive whites. Since ET-1 might play a significant role in
      the development and severity of hypertension in the indigenous Arab population of
      the United Arab Emirates, we investigated the circulating levels of ET-1 in this
      homogenous population. PATIENTS AND METHODS: ET-1 levels were measured in plasma
      samples from 60 untreated hypertensive Arabs and compared with 60 age- and sex
      matched normotensive controls. RESULTS: ET-1 levels were significantly higher in
      hypertensives (mean 10.1 +/- 1 pmol/L) than normotensives (mean 2.2 +/- 0.5
      pmol/L). Body mass index (BMI) was slightly higher among the hypertensives. For
      all subjects these levels significantly (P < 0.001) correlated with systolic
      blood pressure and less significantly (P < 0.05) with diastolic blood pressure
      and body weight. The correlation between ET-1 and both systolic and diastolic
      blood pressure was persistently significant after adjusting for BMI. CONCLUSION:
      Plasma concentrations of ET-1 are significantly higher in hypertensive Gulf Arabs
      as compared with reported levels in white hypertensives and ET-1 could be a risk
      factor for cardiovascular diseases in this population. The endothelial system
      might be particularly important with respect to hypertension in this racial group
      and merits further study.

PMID- 17019100
TI  - Peripheral neuropathy in thalassaemia.
AB  - BACKGROUND: Patients with thalassemia may complain of numbness and weakness of
      the lower extremities. The aim of the study was to document whether these
      patients suffer from a polyneuropathy and to determine any contributing factors
      for the development of neuropathy. PATIENTS AND METHODS: We examined 30 patients
      with thalassemia major and intermedia, clinically and electrophysiologically. We
      correlated these findings with demographics, blood status, and treatment and
      compared electrophysiologic data with 30 age- and sex-matched normal subjects or
      historical controls. RESULTS: We found that 78% of thalassemic patients suffered
      from a mild sensory polyneuropathy. The neuropathy seemed to be worse in the
      intermedia type. Thalassemic patients who received blood transfusions and
      deferoxamine had better nerve function than those who did not, irrespective of
      the dose of deferoxamine. The neuropathy was worse for older patients,
      irrespective of sex. The hemoglobin level, and the fact that some patients
      underwent splenectomy, did not affect the status of the patients' nerves.
      CONCLUSION: Patients with thalassemia may suffer from a sensory polyneuropathy
      especially as they grow older and if they are not optimally treated.

PMID- 17019101
TI  - Peeling skin syndrome: 11 cases from Saudi Arabia.
AB  - BACKGROUND: Peeling skin syndrome (PSS) is a rare genodermatoses of probable
      autosomal recessive inheritance. In Saudi Arabia, consanguinity of parents is
      common and consequently the occurrence of familial disease, including that of the
      skin, is not uncommon. METHODS: To characterize the clinical and pathological
      features of PSS in Saudi Arabia, we reviewed the medical records and clinical
      photographs of patients with recurring blistering diseases and conducted a
      histopathologic evaluation of skin biopsies to identify the site of cleavage.
      RESULTS: Eleven patients with PSS were seen at King Khalid National Guard
      Hospital in Jeddah between the years 1986 and 2005. Ages ranged between 2 and 15
      years and there were 9 males (81.8%) and 2 females (18.2%). The most common
      presentation in the majority of patients was localized spontaneous peeling of the
      skin. Eight patients (72.7%) had a history of vesicles that were small, dry and
      peeled away. Trauma did not play a role in blister formation. All patients were
      local from Bedouin tribes where a family history of a similar complaint was
      documented in 8 cases (72.7%) and consanguinity of marriage was evident in 6
      patients (54.5%). Histological examination of skin biopsies showed either
      intracorneal or superficial subcorneal cleavage above the granular layer in all
      biopsied patients. CONCLUSION: Although rare, PSS occurs in Saudi Arabia and is
      most likely related to consanguinity of marriages. This disease is generally mild
      and is characterized by intracorneal cleavage within the superficial epidermis.
      The disease should be recognized and not confused with other vesicobullous
      disease.

PMID- 17019102
TI  - Causes of hospitalization of pilgrims in the Hajj season of the Islamic year 1423
      (2003).
AB  - BACKGROUND: Approximately 2 to 3 million pilgrims perform Hajj every year.
      Planning for health care requires knowledge of the pattern of diseases,
      complications, and outcome of pilgrims who require hospitalization during the
      Hajj period. METHODS: In a cross-sectional study we compiled data on all patients
      admitted to 1487 beds in four hospitals in Mena (793 beds) and three hospitals in
      Arafat (694 beds) from the seventh to the thirteenth day of the Hajj season of
      the Islamic year 1423, corresponding to 8 to 14 February 2003. RESULTS: Of 808
      patients hospitalized, most (79%) were older than 40 years. There was no sex
      preponderance. A total of 575 (71.2%) patients were admitted to medical wards,
      105 (13.0%) to surgical wards, and 76 (9.4%) to intensive care units. Most
      patients (84.8%) had one acute medical problem. Pneumonia (19.7%), ischemic heart
      disease (12.3%), and trauma (9.4%) were the most common admitting diagnoses. More
      than one third (39%) had co-morbid conditions. A total of 644 (79.7%) patients
      were discharged from the hospital in stable condition to continue therapy in
      their residential camps, 140 (17.3%) were transferred to other hospitals in
      Makkah for specialized services or further care, 19 (2.3%) were discharged
      against medical advice, and 5 (0.7%) patients died. CONCLUSION: This study
      provided information on the most common causes of hospitalization, pattern of
      diseases, and required medical services for pilgrims in Hajj. It is hoped that
      this data will be of help to health sector planners and officials to provide
      optimal and cost-effective health care services to pilgrims in Hajj.

PMID- 17019103
TI  - The endothelium and endothelin: beyond vascular reactivity.

PMID- 17019104
TI  - Are opioids contraindicated as postoperative pain relief for patients who are
      breast-feeding their newborn?

PMID- 17019105
TI  - New insights in hypertensive disorders of pregnancy.
AB  - Research reported during the past year has enhanced our understanding of
      conditions that lead to the complex changes that are observed in hypertensive
      disorders of pregnancy. An association between placental pathology and a
      multisystem disorder that is characterized by endothelial dysfunction which
      involves genetic and immunological investigations has been identified. On the
      basis of these findings, promising screening tools for early detection of pre
      eclampsia were identified. No marked changes in anaesthetic approach to
      hypertensive disorders of pregnancy occurred during the period of review, apart
      from a reappraisal of spinal anaesthesia as a safe technique in caesarean
      section, even in patients with severe pre-eclampsia. A multidisciplinary approach
      to management and therapy is needed and the right balance must be sought between
      the needs of the mother and baby, both of which are jeopardized by the
      hypertensive disorders of pregnancy.

PMID- 17019106
TI  - Medical and obstetric problems complicating pregnancy.
AB  - The present review addresses several medical and obstetric factors/problems, and
      their interactions during pregnancy. These include the following: maternal age;
      morbidity and mortality during pregnancy; thromboembolism; gestational diabetes;
      haemolysis, elevated liver enzymes, low platelets syndrome; human
      immunodeficiency virus; hepatitis C; preterm labour; antenatal administration of
      corticosteroids; intrapartum surveillance; breech delivery; and caesarean
      section.

PMID- 17019107
TI  - Anaesthesia for caesarean section.
AB  - Although anaesthesia for Caesarean section is predominantly performed using
      regional techniques of anaesthesia, general anaesthesia will remain essential for
      subgroups of obstetric patients, especially those who are at high risk of
      complications. In the present review, recent reports that addressed issues
      regarding general and regional anaesthesia in Caesarean section will be
      discussed.

PMID- 17019108
TI  - Pharmacological considerations during pregnancy.
AB  - We present a brief overview of recent literature concerning some of the drugs
      used in pregnancy, labour and delivery. Obstetric anaesthesia continues to evolve
      through the reuse of old drugs such as magnesium sulphate or the manipulation of
      current drugs (e.g. propofol for emesis) in order to improve patient outcome.
      Pregnant women have traditionally been therapeutic orphans. The use of new agents
      such as levobupivacaine and ropivacaine in obstetric patients lags behind that of
      their non-pregnant counterparts. However, this gap is decreasing and these new
      drugs offer benefits to the parturient woman.

PMID- 17019109
TI  - Complications of obstetric anaesthesia.
AB  - The present review addresses common and rare, but potentially severe
      complications of obstetric anaesthesia. Although several recent randomized and
      controlled studies on the prevention of spinal hypotension have been reported,
      the incidence of neurological complications caused by neuraxial blocks is
      estimated primarily from the results of retrospective investigations and case
      reports. In order to avoid potential risks in obstetrics, however, vigilance and
      close monitoring of the patient are critical. The adoption of published
      recommendations (e.g. those regarding regional techniques and coagulopathy, and
      difficult airway management) may help to improve the outcome for mother and
      child.

PMID- 17019111
TI  - Outcome after minor surgery in children.
AB  - Major complications and death are rare events, but cases are reported even in
      connection with minor surgery. Most of the patients for 'minor' surgery are
      currently treated as day cases and during the hospital stay only the immediate or
      intermediate outcome is seen. The results of the evaluations on the late outcome
      at home can be surprising.

PMID- 17019112
TI  - Premedication and parental presence revisited.
AB  - Up to 60% of all children undergoing anesthesia and surgery experience
      significant anxiety and distress during the perioperative period. Currently, both
      behavioral interventions such as parental presence during induction of anesthesia
      and pharmacological interventions such as sedative premedication are used to
      treat this clinical phenomenon. In this review, we examine the effectiveness of
      these interventions on clinically relevant perioperative outcomes.

PMID- 17019113
TI  - Excitation phenomena during sevoflurane anaesthesia in children.
AB  - The advantages of rapid induction of and emergence from sevoflurane anaesthesia
      may be more than offset by the frequent occurrence of agitation during induction
      and recovery, and a possible epileptogenic effect. The mechanisms and possible
      strategies to prevent these drawbacks are reviewed, on the basis of the most
      recent literature.

PMID- 17019114
TI  - New insights into regional anesthesia in children: new techniques and new
      indications.
AB  - The applications and indications for pediatric regional anesthesia continue to
      increase. Several recent advances have occurred in the understanding of this
      technology in children, including improved techniques, alternative drug
      combinations, as well as prospective investigations to understand the nature and
      incidence of adverse effects associated with these techniques when used in
      pediatric patients. The following article will review recent information from the
      literature concerning various regional anesthetic techniques in children,
      including caudal epidural block, lumbar and thoracic epidural anesthesia, and
      peripheral nerve blockade.

PMID- 17019115
TI  - New insights into paediatric regional anaesthesia: new drugs.
AB  - Over the years paediatric regional anaesthesia has gained a worldwide consensus,
      and it can now be considered a significant part of perioperative pain control in
      children. As in many fields, with the use of drugs administered epidurally there
      is a fundamental need for safety and efficacy. Two new local anaesthetic agents
      have recently entered the market, ropivacaine and levobupivacaine, which seem to
      offer a wider safety margin in comparison with the old drugs as well as valid
      pain control. To prolong their analgesic duration, many adjuvants can be used,
      and clonidine and ketamine are probably the best solution. This review summarizes
      the most recent data on these drugs and their use in children.

PMID- 17019116
TI  - Sedation and analgesia for procedures outside the operating room in children.
AB  - There has been a dramatic increase in the number of procedures that are conducted
      in children in which sedation is now considered beneficial. In many institutions,
      however, resources and personnel have not been recruited to address this increase
      in demand. In most institutions, anaesthesiology departments are not able to
      provide anaesthesia for all procedures that are performed outside the operating
      theatre, and alternative solutions are needed. Recent research includes attempts
      to decrease the time required to induce sedation and to recover from it, and
      development of new organizational models to improve the safety of procedural
      sedation.

PMID- 17019117
TI  - Current world literature.

PMID- 17019118
TI  - Drugs and haemostasis.

PMID- 17019119
TI  - Inhalational anaesthesia.
AB  - Sevoflurane and desflurane have important advantages over isoflurane and
      halothane. Disadvantages, which the clinician should keep in mind, include the
      degradation of both agents by soda lime under certain circumstances during closed
      circuit anaesthesia. As a result compound A and carbon monoxide (CO) may be
      generated in soda lime canisters and may be inhaled by patients. The extent to
      which this constitutes a significant problem during routine anaesthesia in humans
      is not clear. Recent developments in absorbent technology have the potential to
      reduce any hazard to negligible proportions. Other undesirable properties of the
      newer inhalation agents include agitation with sevoflurane in children and
      cardiovascular and airway effects with desflurane.

PMID- 17019120
TI  - Intravenous anesthetics.
AB  - Intravenous anesthetics continue to be a mainstay in the modern
      anesthesiologist's armamentarium. In this review the authors will discuss new
      advancements in the use of propofol, as well as a greater understanding as to its
      mechanism of action. Further, we will discuss the use of target controlled
      infusion systems, touch upon the possible benefits of the ultra-short acting
      opioids, and consider the role of alpha-2 agonists as an adjunct to anesthetic
      management.

PMID- 17019121
TI  - Update on neuromuscular pharmacology.
AB  - Since the introduction of d-tubocurarine into clinical practice, neuromuscular
      relaxants have been widely used in anaesthesia. Although their clinical use is
      easy, several points still require further attention and research. There is still
      a need for a drug with the clinical profile of succinylcholine but fewer unwanted
      side-effects. A better understanding of the effects of muscle relaxants on
      different muscles could help in their clinical use during the perioperative
      period. Much knowledge is needed about residual neuromuscular block and its
      detection in order to improve the quality of recovery from neuromuscular
      blockade. If some questions remain to be answered, several recent articles have
      increased our knowledge and should improve our clinical practice.

PMID- 17019122
TI  - Recent advances in opioid pharmacology.
AB  - Despite their many and sometimes life-threatening side-effects, opioids in
      general and morphine in particular are valuable and potent painkillers. This
      article describes recent developments in sex-related differences in opioid
      (morphine) pharmacodynamics, morphine metabolites, the nociceptin/orphanin FQ
      receptor system, acute opioid tolerance and opioid-induced side-effects, such as
      opioid-induced respiratory depression and itch, and P-glycoprotein modulation of
      opioid effect.

PMID- 17019123
TI  - Drug interactions.
AB  - The prevalence of undesirable drug interactions is substantial but largely
      unknown. Although drug interactions are certainly an important cause of drug
      toxicity, their clinical significance may have been exaggerated. This review
      presents a brief overview of possible drug interactions.

PMID- 17019124
TI  - Management of acute and postoperative pain.
AB  - The optimal management of postoperative pain is a prerequisite for early recovery
      and shorter hospital stays. The use of multimodal analgesia techniques involving
      the use of opioid and non-opioid (local anesthetics, ketamine, acetaminophen, and
      non-steroidal anti-inflammatory drugs) analgesic drugs can markedly enhance pain
      relief in the perioperative period.

PMID- 17019125
TI  - In-hospital resuscitation.
AB  - A recent world expert conference on resuscitation and emergency cardiac care led
      to evidence-based international guidelines for cardiopulmonary resuscitation
      (CPR). Several changes to CPR interventions were recommended, and will have to be
      implemented into clinical practice. The poor prognosis of patients who suffer in
      hospital cardiac arrest may be improved with developments in CPR interventions.
      In the present review the most important changes recommended by the new CPR
      guidelines and the latest promising CPR investigations are described, focusing on
      their impact on in-hospital resuscitation.

PMID- 17019126
TI  - Resuscitation, anaesthesia and analgesia of the burned patient.
AB  - Burns resuscitation has evolved over the past few decades towards more evidence
      based management. It has been shown that patients with major burns (i.e.
      involving more than 30% of the body surface) benefit from invasive monitoring,
      and physiological variable targeted resuscitation using vasoactive agents for
      cardiovascular support. The invasive approach results in a reduction of mortality
      rates. Since the introduction of the Parkland formula in 1968, there has been a
      trend towards the administration of fluid resuscitation far in excess of the
      volume predicted with this formula. This has led to an increase in complication
      rates, with more pulmonary oedema, and the appearance of abdominal compartment
      syndrome. Hypertonic saline solutions, whether with dextran or not, have shown no
      advantage over the classic Ringer's lactate solution. The colloid controversy has
      reached burns resuscitation, with the demonstration that the liberal use of
      albumin is associated with higher mortality rates. Fresh frozen plasma should
      only be used for specific coagulation disorders. On the other hand, artificial
      colloids, particularly gelatine, remain a useful tool in patients with major
      burns and haemodynamic instability, particularly, and can be given as early as 6
      h after injury. Considering the actual evidence, using inotropes and vasopressors
      to reach supranormal haemodynamic endpoints seems preferable to delivering
      unrestricted amounts of fluid.

PMID- 17019127
TI  - Paediatric anaesthesia outside the operating room.
AB  - Anaesthesiologists are regularly consulted to provide anaesthesia for children in
      settings other than an operating room. Current debate focuses on the
      appropriateness of the presence of an anaesthesiologist versus a non
      anaesthesiologist. There is mounting evidence that the presence of an
      anaesthesiologist is safer. We will review the recent literature concerning
      paediatric anaesthesia outside the operating room and offer recommendations that
      may impact on efficacy and safety.

PMID- 17019128
TI  - Management of paediatric patients undergoing diagnostic and invasive cardiology
      procedures.
AB  - Since diagnostic cardiac catheterization in children with congenital heart
      disease was first reported in 1947, echocardiography has been used as a non
      invasive diagnostic tool in congenital heart disease, resulting in a decrease in
      diagnostic cardiac catheterizations. However, the total number of cardiac
      catheterizations remained at a steady level until the mid-1980s and has since
      increased progressively. This is a result of the introduction of interventional
      transcatheter techniques to improve or correct congenital heart malformations.
      Since the first description of balloon atrial septostomy, the range of
      indications for such techniques has steadily increased, particularly in the past
      15 years. 'Deep' sedation or general anaesthesia is essential for the conduct of
      cardiac catheterization in children, particularly in the younger age group.

PMID- 17019129
TI  - Anaesthesia for procedures in the intensive care unit.
AB  - Taking in charge severely ill patients in the intensive care environment to
      manage complex procedures is a performance requiring highly specific knowledge.
      Close collaboration between anaesthetists and intensive care specialists is
      likely to improve the safety and quality of medical care. Three forms of
      anaesthetic care should be considered in clinical practice: sedation and
      analgesia; monitored anaesthetic care; and general anaesthesia or conduction
      block anaesthesia. Even in the field of sedation and analgesia, the
      anaesthesiologist can offer expertise on new anaesthetic techniques like: the
      most recent concepts of balanced anaesthesia in terms of pharmacokinetics and
      dynamics, favouring the use of short-acting agents and of sedative-opioid
      combinations. New modes of administration and monitoring intravenous anaesthesia
      have been developed, with potential application in the intensive care unit. These
      include the use of target-controlled administration of intravenous drugs, and of
      electroencephalographic signals to monitor the level of sedation.

PMID- 17019130
TI  - Current world literature.

PMID- 17019132
TI  - Aspects of stroke management including subarachnoid haemorrhage.
AB  - The present review focuses on some aspects of stroke management and covers
      important clinical studies and studies in basic research published during the
      past year. It is subdivided in three sections. First, we focus on ischaemic
      stroke and discuss some new insights into the genetics of ischaemic stroke,
      intensive stroke care including cerebral thrombolysis, and neuroprotective
      treatment. Secondly, new insights into the risk factors and outcome of primary
      and iatrogenic intracerebral haemorrhage are discussed. Finally, we review in the
      section on subarachnoid haemorrhage literature on the further development of
      endovascular treatment of cerebral aneurysms, and research into the causes of
      vasospasms and secondary cerebral ischaemia.

PMID- 17019133
TI  - The acute care of traumatic brain injury.
AB  - During the past few decades, management of acute traumatic brain injury has
      advanced substantially on several fronts. Implementation of rapid transport
      systems and the advent of trauma centres, together with advances in emergency
      medicine, critical care medicine and trauma neurosurgery, have improved outcome
      following head injury. Technological advances made during the past years in the
      field of invasive neuromonitoring that provide real-time information on brain
      oxygenation may further improve outcome by enabling individualized therapies for
      intracranial hypertension. Furthermore, these recent technological advances will
      provide insights into the pathophysiological processes that are active in
      traumatic brain injury and a better understanding of the biochemical effects of
      specific therapeutic regimens.

PMID- 17019134
TI  - Anaesthetic management of neurosurgical patients.
AB  - Anaesthetic care of neurosurgical patients increasingly involves management
      issues that apply not only to 'asleep patients', but also to 'awake and waking-up
      patients' during and after intracranial operations. On one hand, awake brain
      surgery poses unique anaesthetic challenges for the provision of awake brain
      mapping, which requires that a part of the procedure is performed under conscious
      patient sedation. Recent case reports suggest that local infiltration anaesthesia
      combined with sedative regimens using short-acting drugs and improved monitoring
      devices have assumed increasing importance. These techniques may optimize rapid
      adjustments of the narcotic depth, providing analgesia and patient immobility yet
      permitting a swift return to cooperative patient alertness for functional brain
      tests. Regional anaesthesia and peripheral nerve blocks were used to prevent
      uncontrolled movements in special cases of intractable seizures. However, few of
      these strategies have been evaluated in controlled trials. Awake craniotomy for
      tumour removal is performed as early discharge surgery. Meticulous consideration
      of postoperative patient safety is therefore strongly advised. On the other hand,
      waking-up patients or the emergence from general anaesthesia after brain surgery
      is still an area with considerable variation in clinical practice. Developments
      indicate that fast-acting anaesthetic agents and prophylactic strategies to
      prevent postoperative complications minimize the adverse effects of anaesthesia
      on the recovery process. Recent data do not advocate a delay in extubating
      patients when neurological impairment is the only reason for prolonged
      intubation. An appropriate choice of sedatives and analgesics during mechanical
      ventilation of neurosurgical patients allows for a narrower range of wake-up
      time, and weaning protocols incorporating respiratory and neurological measures
      may improve outcome. In conclusion, despite a lack of key evidence to request
      'fast-tracking pathways' for neurosurgical patients, innovative approaches to
      accelerate recovery after brain surgery are needed.

PMID- 17019135
TI  - Neuroprotection with anaesthetic agents.
AB  - The term 'neuroprotection' is used to refer to any prophylactic measure that is
      initiated during the peri-ischaemic period in order to improve neuronal survival.
      Cell death after ischaemia has an immediate, necrotic and a delayed, apoptotic
      origin. The major biochemical mechanisms that are involved in this process
      include transmembrane ionic fluxes and intracellular calcium increase,
      excitotoxicity, free radical formation, peroxynitrite production, release of
      inflammatory mediators, mitochondrial dysfunction, cytochrome c release, and
      activation of caspases and transcription factors. Strategies of neuroprotection
      essentially impact on those biochemical pathways. The label 'neuroprotectant'
      requires that the therapy has basic properties that are consistent with potential
      mechanisms of neuroprotection, and that conclusive results are available from
      animal studies that can be converted into clinical benefit. The present review
      focuses on neuroprotective effects of anaesthetics and is based on the most
      recently published reports.

PMID- 17019136
TI  - Anti-tumor agents for neuropathic pain: switching roles?

PMID- 17019137
TI  - Preemptive analgesia: an unsolved problem.
AB  - Preemptive analgesia studies have provided mixed results, some showing benefit
      and others no benefit, whereas others have shown small differences that are
      probably not clinically useful. There is no consensus yet about whether
      preemptive analgesia is a clinically useful tool. This review examines the
      mechanisms of preemptive analgesia before surveying the recent literature. A new
      definition of preemptive analgesia is proposed that accommodates the need for a
      broader definition. Recently published trials confirm that confusion exists about
      what preemptive analgesia is, how to distinguish it from simple analgesia, and
      how to design trials that truly assess preemptive analgesia, defined as analgesia
      that is capable of modifying the central excitatory responses.

PMID- 17019138
TI  - New developments in the use of tricyclic antidepressants for the management of
      pain.
AB  - In recent years, tricyclic antidepressant drugs have experienced a resurgence in
      their use as valuable pharmacological tools in the treatment of pain. Along with
      the evolution in our understanding of their analgesic mechanisms of action, there
      have been concurrent breakthroughs regarding their indications for use and modes
      of administration. This review focuses on recent advances in our understanding of
      how antidepressant drugs exert their antinociceptive effects, and new
      developments regarding their clinical application.

PMID- 17019139
TI  - Alpha(2) receptors and agonists in pain management.
AB  - Alpha(2) agonists have been in clinical use for decades, primarily in the
      treatment of hypertension. In recent years, alpha(2) agonists have found wider
      application, particularly in the fields of anesthesia and pain management. It has
      been noted that these agents can enhance analgesia provided by traditional
      analgesics, such as opiates, and may result in opiate-sparing effects. This has
      important implications for the management of acute postoperative pain and chronic
      pain states, including disorders involving spasticity or myofascial pain,
      neuropathic pain, and chronic daily headaches. The clinical utility of these
      agents is ever expanding, as they are gaining broader use in neuraxial analgesia,
      and new applications are continuously under investigation. The alpha(2) agonists
      that are currently employed in anesthesia and pain management include clonidine,
      tizanidine, and dexmedetomidine. Moxonidine and radolmidine, which are not
      currently in clinical use in humans, may offer favorable side-effect profiles
      when compared with traditional alpha(2) agonists, and may thereby allow for more
      widespread pain management applications.

PMID- 17019140
TI  - Inflammatory pain: kinins and antagonists.
AB  - This short review focuses on the most recent findings in the rapidly expanding
      field of kinin research. Through a series of recent publications, the crucial
      relevance of this group of peptides as mediators of inflammatory pain is becoming
      increasingly evident. On the strength of this idea, kinins have been implicated
      as algogen peptides produced in response to noxious stimuli. The importance of
      kinins has been elucidated by different pharmacological and molecular approaches.
      Special attention has been given to studies with selective kinin antagonists, as
      well as to the use of receptor gene deletion technology. The gathering of results
      has demonstrated that both B(1) and B(2) receptors seem to exert a meaningful
      role during nociceptive responses, the B(1) receptor being most relevant in the
      chronic stages of inflammatory pain. It is hoped that new effective and useful
      therapeutic agents, mainly B(1) kinin selective receptor antagonists, might soon
      be available.

PMID- 17019141
TI  - Cyclooxygenase-2 and antagonists in pain management.
AB  - Non-steroidal anti-inflammatory drugs are widely used for the treatment of pain
      and inflammation by inhibiting the formation of prostaglandins. However, their
      use is limited by their side-effects, including gastrointestinal, renal function,
      cardiovascular and platelet function. Cyclooxygenase activity is the principal
      target for the action of non-steroidal anti-inflammatory drugs. Two isoforms of
      cyclooxygenase have been characterized: (i) cyclooxygenase-1, which is found in
      many tissues and is generally constitutively expressed and synthesizes
      prostanoids that mediate homeostatic functions; and (ii) cyclooxygenase-2, the
      inducible isoform, which is mainly expressed at sites of injury or inflammation
      and synthesizes prostanoids that mediate inflammation, pain and fever. These
      findings led to the development of selective cyclooxygenase-2 inhibitors, with
      comparable anti-inflammatory and analgesic properties to traditional non
      steroidal anti-inflammatory drugs, but with significantly fewer side-effects.
      However, these new selective cyclooxygenase-2 inhibitors are not risk free, and
      care should be taken when using these drugs, especially with elderly patients
      with multiple medical problems. Finally, the future is bright for the broader
      usage of these agents in the treatment of diseases other than inflammation and
      pain, such as Alzheimer's disease, colonic polyp and colon cancer, just to name a
      few.

PMID- 17019142
TI  - Fibromyalgia: diagnosis, pathogenesis, and treatment.
AB  - Fibromyalgia is characterized by chronic widespread pain and the presence of
      tender points, often accompanied by several non-specific symptoms, such as
      fatigue, depressive mood, and sleep disturbances. The apparent overlap between
      fibromyalgia and other syndromes, such as chronic fatigue and irritable bowel, is
      not sufficient cause to consider all these syndromes as manifestations of a
      single syndrome. Fibromyalgia is a multifaceted problem. Central afferent pain
      amplification and perhaps also impaired descending pain inhibition are supposed
      to underlie widespread pain. Neuroendocrine perturbations, sleep disturbances,
      health beliefs, mood disorder, and physical deconditioning play a role in the
      modulation and perseverance of pain and other symptoms. It is extremely difficult
      to mitigate chronic generalized pain and to deal with other symptoms in
      fibromyalgia. A uniform intervention strategy is missing. Essential in the
      tailored management of fibromyalgia are an enhancement of functional capacities
      and quality of life, and the symptomatic treatment of individual symptoms such as
      pain, distress, and sleep disturbances. Rather than analysing monotherapy per se,
      the objective in future evaluations should be to try to find the combined
      pharmacological or non-pharmacological treatment of choice for specific subgroups
      of patients.

PMID- 17019143
TI  - Complex regional pain syndrome.
AB  - Despite its recommendation by the International Association for the Study of
      Pain, the term 'complex regional pain syndrome' has not been widely adopted. Most
      authors still prefer the term 'reflex sympathetic dystrophy'. The diagnostic
      criteria recommended by the International Association for the Study of Pain have
      been criticized as lacking specificity, and refined criteria have been proposed.
      The pathophysiology of the complex regional pain syndrome remains elusive, but
      most recent work favours a central mechanism both for the sensory features and
      the autonomic features. Peripheral mechanisms include tissue acidosis. Some
      investigators, however, view the condition as psycho-neurogenic. Although
      recommended by some, laboratory tests add little to diagnostic confidence.
      Certain prophylactic measures have been recommended for patients undergoing
      surgery, and for the treatment of fractures of the radius. Treatment is still
      based largely on traditional wisdom. Some new treatments have been promoted on
      the basis of uncontrolled studies. Controlled studies have indicated possible
      roles for bisphosphonates and spinal cord stimulation.

PMID- 17019145
TI  - Ethics of organ transplantation in Japan: an example of cultural transplantation
      in medicine.
AB  - Since the passage of the Organ Transplant Law in October 1997, only nine persons
      declared dead by neurological criteria have donated their organs in Japan. This
      article is an attempt by Japanese anesthesiologists to introduce the cultural and
      moral justification of Japanese transplant practice to the international
      community.

PMID- 17019146
TI  - Do not resuscitate orders in different countries.
AB  - Health care decision making in severely ill patients presents many difficult
      medical, ethical and legal problems. Physicians, including anaesthesiologists,
      are frequently confronted with dilemmas regarding the appropriateness of risky
      interventions and the balance of potential benefits versus risks. The risks
      include not only death and the pain and suffering that are related to the
      interventions, but also (and arguably more importantly) the burdens of lingering
      disability, loss of independence and poor quality of life. This review presents
      recent findings (focusing on papers published between 1999 and March 2001), and
      explores the background for the introduction of do not resuscitate policies and
      their use in clinical practice in different countries. Problems with auditing and
      implementing do not resuscitate policies are highlighted.

PMID- 17019147
TI  - Economics of preoperative evaluation clinics.
AB  - Studies continue to support that a process for screening patients prior to their
      planned anesthesia and surgery can optimize both the status of the patient,
      decreasing delays and cancellations, and optimize the use of resources, ensuring
      that needed testing is completed and unneeded testing is avoided.

PMID- 17019148
TI  - Economics of antiemetics in anesthesia.
AB  - The optimal strategy for prevention and treatment of postoperative nausea and
      vomiting remains uncertain. In the present review we examine the evidence that
      prophylactic antiemetics increase patient satisfaction and reduce costs in
      selected cases, as compared with a strategy of waiting for symptoms to develop
      and then administering treatment. Finally, evidence in favor of a specific
      antiemetic drug and dose are scrutinized, and an overall guideline for treatment
      is developed.

PMID- 17019149
TI  - Cost-effectiveness of anaesthesia.
AB  - Cost-effectiveness analyses of anaesthesia regimens will become more and more
      important in the future because of increasing pressure to reduce the cost of
      health care. Inhalational and intravenous techniques are vying for the position
      of being the most cost-effective form of general anaesthesia. However, erroneous
      or misleading results are a considerable risk if the boundary conditions of the
      analyses are not chosen carefully. Recent comparative studies on this topic are
      analyzed with regard to their results and to the premises under which they were
      conducted.

PMID- 17019150
TI  - Effect of return hospital visits on economics of ambulatory surgery.
AB  - This review examines the effect of unanticipated admission, return hospital
      visits and readmission on the economics of ambulatory surgery. The overall rate
      of unanticipated admission was approximately 1% and the overall rate of
      readmission to hospital was approximately 1%. Ambulatory surgery allows total
      cost savings of 20-50% when compared with inpatient surgery. If 98% of ambulatory
      surgery patients experience uneventful recovery, the decrease in cost savings
      caused by unanticipated admission and return hospital visit is very small.
      Modifications of anesthesia and surgical technique can help to further reduce the
      incidence of unanticipated admission or readmission to hospital.

PMID- 17019151
TI  - Current world literature.

PMID- 17019152
TI  - The role of spinal anesthesia in the ambulatory venue: current issues and
      concerns.

PMID- 17019153
TI  - Management of outpatient orthopedic surgery.
AB  - The past few years have witnessed tremendous growth in the number and complexity
      of orthopedic surgical procedures performed on an outpatient basis. Despite these
      advances, postoperative pain remains a significant problem that may limit further
      expansion of outpatient orthopedic surgery. Regional anesthesia plays an
      important role in day case surgery facilitating fast-tracking, accelerating
      discharge, reducing unexpected hospital admissions, and providing prolonged pain
      relief. Continuous peripheral nerve blockade, now possible in this setting,
      provides excellent perioperative care, with high patient satisfaction and
      improved rehabilitation scores.

PMID- 17019154
TI  - Management of outpatient ear, nose and throat surgery.
AB  - In the year under review there have been steady advances in anaesthesia.
      Premedication in children is best achieved with oral midazolam formulated in
      flavoured syrups, and the inhalational induction of anaesthesia may be
      accomplished using sevoflurane. Pain management of the most common surgical
      procedure performed in children, tonsillectomy/adenoidectomy, is still sub
      optimal, but combinations of opioids and non-steroidal anti-inflammatory drugs
      are helpful. There are, however, some concerns regarding the possible increases
      in postoperative blood loss after tonsillectomy when non-steroidal anti
      inflammatory drugs are used. Middle ear surgery leads to a high incidence of
      postoperative nausea and vomiting, and these are best managed by utilizing a
      total intravenous anaesthetic technique with propofol, the avoidance of nitrous
      oxide, and administration of dexamethasone and a 5-hydroxytryptamine receptor
      antagonist such as ondansetron.

PMID- 17019155
TI  - How can we best prevent or treat postoperative nausea and vomiting?
AB  - In pursuit of preventing or rapidly rescuing patients from postoperative nausea
      and vomiting, new clinical studies provide revised postoperative nausea and
      vomiting risk prediction tools, risk stratification formulae, comparative trials
      to identify the most appropriate cost-effective anti-emetics, and several trials
      recommending the addition of steroids in anti-emetic prophylactic multimodal
      approaches. Common variables that identify high-risk postoperative nausea and
      vomiting patients include female sex, a history of postoperative nausea and
      vomiting or motion sickness, young age, volatile anesthetic agents, nitrous
      oxide, and the administration of opioids. The most successful approach to the
      prevention of postoperative nausea and vomiting is multimodal, with combination
      anti-emetics, dexamethasone, aggressive hydration, the avoidance of opioids, and
      aggressive pain control.

PMID- 17019156
TI  - Anesthesia for diagnostic procedures.
AB  - Anesthetists and other providers are seeing an increased demand for sedation or
      anesthesia for challenging patients undergoing diagnostic procedures. Regardless
      of the specialty of the provider, proper attention must be paid to patient
      evaluation, monitoring, and drug dosage. The present review summarizes
      recommendations regarding sedation, as well as recent literature on sedation and
      anesthesia for endoscopy, radiology, pediatric oncology procedures, and pediatric
      electroencephalography.

PMID- 17019157
TI  - Fast-tracking in outpatient surgery.
AB  - Fast-tracking in outpatient surgery is a new paradigm that allows for rapid
      throughput and early discharge, thereby facilitating perioperative efficiency.
      Compared with the conventional recovery process, bypassing the postanesthesia
      care unit reduces the time to discharge home. An ideal anesthetic technique for
      fast-tracking would provide for rapid emergence and the prevention of common
      postoperative complications such as pain, nausea, and vomiting using a multimodal
      approach.

PMID- 17019159
TI  - Computerized anaesthesia information management systems: are we on the threshold
      of widespread use?
AB  - Despite a recognition that they are essential for the future progress of
      anaesthesia, computerized anaesthesia information management systems are not in
      widespread use. In this article, relevant recent publications are summarized with
      a view to identifying the reasons for the current situation. Several developments
      which might promote the wider use of such systems in the near future are also
      presented.

PMID- 17019160
TI  - Monitoring depth of anesthesia.
AB  - Devices which monitor some aspect of anesthetic drug effects have evolved in the
      past few years into imperfect, but very useful, clinical tools. With appropriate
      respect for their limitations these monitors can be used to reduce anesthetic
      drug utilization and turnover time. The intriguing hypothesis that such monitors
      will reduce the risk of intraoperative awareness is currently under test.

PMID- 17019161
TI  - Neuromuscular monitoring.
AB  - This review summarizes recent reports on the techniques and the use of methods
      for monitoring neuromuscular function during anaesthesia. The latest news on the
      use of acceleromyography in the face and hand, on laryngeal and diaphragmal
      surface electromyography, on acoustic myography, on evaluation of intense
      neuromuscular block, and on postoperative residual curarization is presented and
      discussed. It is concluded that available evidence suggests that more attention
      should be paid by the anaesthetist to the problems of residual curarization and
      hence to proper monitoring of neuromuscular function using objective methods.

PMID- 17019162
TI  - Multiple choice questions: their value as an assessment tool.
AB  - Multiple choice questions are a well-established, reliable method of assessing
      knowledge and are used widely in postgraduate examinations in anaesthesiology.
      Like other methods of assessment they have their strengths and weaknesses. With
      the drive for revalidation and changes in undergraduate medical education much
      work has been done on devising valid, reliable and feasible methods of assessment
      of clinical practice including the need for the use of several different methods.
      Different multiple choice question formats have been devised and the importance
      of well-written multiple choice questions with clear assessment objectives
      recognized. There is controversy about the use of number-right as opposed to
      negative marking but, provided that the candidates know which marking system is
      being used, either method is satisfactory. The pass standard should be determined
      using criterion-based rather than norm-based referencing. Multiple choice
      questions could be used to validate continuing education and professional
      development from reading, possibly using web-based technology. For as long as
      there is a need to test knowledge in the assessment of doctors and medical
      undergraduates multiple choice questions will have a part to play, but only as
      one component of the assessment of clinical competence.

PMID- 17019163
TI  - Herbal medicine and anesthesia.
AB  - Complementary and alternative medicine is one of the fastest growing areas in
      health care. Many patients worldwide utilize these additional health care
      strategies in conjunction with standard medical therapies. Unfortunately little
      is understood about many of the interactions that can occur and as many as 50% of
      the patients do not inform their health care providers about these complementary
      and alternative therapies. The interactions that are most important in the
      perioperative period include sympathomimetic, sedative, and coagulopathic
      effects. Given the overall paucity of information regarding herbal medicines and
      their potential pertinent perioperative implications this domain requires a
      significant amount of further study and in my opinion would be fertile ground for
      federally funded requested projects.

PMID- 17019164
TI  - Perioperative concerns in sleep apnea.
AB  - Sleep apnea syndrome is one of a series of sleep-related breathing disorders, and
      is often under-diagnosed. Recent appreciation of the prevalence of sleep apnea
      and its physiologic effects has raised patient and caregiver awareness of the
      disorder. Few definitive data exist to guide perioperative management of patients
      with sleep apnea. Nevertheless, advances in the study of sleep apnea have served
      to highlight important aspects of anesthetic care for these patients. An improved
      understanding of the relationships between sleep apnea and comorbid conditions
      has better defined the role for preoperative treatment. Recent work has also
      clarified the impact of interactions between postoperative pain management
      strategies and sleep apnea, as well as the need for advanced postoperative
      monitoring. Finally, progress in our understanding of the relationship between
      sleep deprivation and the anesthesized state may provide new insights into
      relationships between the anesthetic and sleep states. The present review
      identifies important perioperative concerns in patients with sleep apnea and
      suggests management strategies.

PMID- 17019165
TI  - Anaesthesia and the elderly.
AB  - As a result of age-related physiological changes and multi-comorbidity, which
      both result in reduced functional reserve of the organ systems, old patients are
      more vulnerable to surgical stress and perioperative impairment in organ
      functions. Therefore, the incidence of severe complications during the
      perioperative course is increased in the elderly. Regional anaesthesia or a
      combination of regional and general anaesthesia is considered to be beneficial in
      elderly patients, because neuraxial blockade may reduce sympathetic activation,
      and has been demonstrated to reduce postoperative mortality. Other protective
      strategies to maintain organ functions in elderly patients include medication
      with beta-blockers in patients with cardiovascular risks, the avoidance of
      hypothermia, the maintenance of systemic oxygen delivery, and patient-controlled
      pain therapy.

PMID- 17019166
TI  - Anaesthetics and immune function.
AB  - Surgical trauma and anaesthetics may cause immune suppression, predisposing
      patients to postoperative infections. Furthermore, stress such as surgery and
      pain per se is associated with immune suppression which, in animal models, leads
      to an increased susceptibility to infection and tumour spread. Thus, by
      modulating the neurohumoral stress response, anaesthesia may indirectly affect
      the immune system of surgical patients. In particular, regional anaesthesia
      attenuates this stress response and the associated effects on cellular and
      humoral immunity. Additionally, anaesthetics may directly affect the functions of
      immune-competent cells. However, the reported effects of commercial preparations
      of, for example, propofol, etomidate and midazolam are highly dependent on the
      applied solvent. Immunosuppressive effects may be particularly relevant in the
      intensive care unit when anaesthetics are used as long-term sedatives. There is a
      striking body of evidence that long-term exposure to certain sedatives is
      paralleled by infectious complications. On the other hand, anti-inflammatory
      effects of anaesthetics may be therapeutically beneficial in distinct situations
      such as those involving ischaemia/reperfusion injury or the systemic inflammatory
      response syndrome. Consequently, sedatives should be administered with careful
      regard to their respective potential immunomodulatory properties, the clinical
      situation, and the immunity status of the critically ill patient.

PMID- 17019167
TI  - Neuromuscular disorders and anesthesia.
AB  - The neuromuscular disorders are associated with diminished cardiopulmonary
      reserves, deficient airway protection mechanisms, and atypical responses to drugs
      used during anesthesia. Many of these conditions are uncommon, and
      methodologically sound evidence to guide clinical practice is limited. The
      disorders discussed in the present review are the motor neuron diseases,
      peripheral neuropathies, myasthenic syndromes, and myopathies, including
      malignant hyperthermia. Recent data on pathogenesis and medical management are
      outlined, as are studies relating to anesthesia and the perioperative period.

PMID- 17019168
TI  - Renal function and dysfunction.
AB  - Recent publications regarding perioperative renal dysfunction provide a
      'potpourri' of topics worthy of discussion. The risk of perioperative renal
      dysfunction is higher in patients with heart failure, but other pre-existing
      conditions, such as genetic polymorphism, may have prognostic implications.
      Evaluation of renal risk and protective interventions are discussed for a number
      of specific operative entities, including cardiac surgery (with or without
      cardiopulmonary bypass), aortic surgery and renal revascularization. New
      publications on a wide variety of nephrotoxic insults are presented, including
      antifibrinolytic agents, obstructive jaundice, prostaglandin inhibitors,
      cyclosporine A, radiocontrast dyes and volatile anesthetic agents. Renal
      transplantation is discussed as a specific entity. Finally, we discuss recent
      papers describing outcome in patients in chronic renal failure undergoing cardiac
      surgery.

PMID- 17019169
TI  - Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery.
AB  - Several studies have demonstrated increased morbidity and mortality in patients
      with cirrhosis undergoing anesthesia and surgery. Cirrhosis is a chronic liver
      disease, which may affect all body systems. The severity of the disease, assessed
      by the Child-Pugh classification, has a substantial effect on patient outcome.
      The extent of surgery and co-morbid conditions also have a major impact. In the
      past few years, changes have been made in the diagnosis, preoperative
      preparation, surgical and anesthetic management and perioperative care of
      patients with liver disease. The aim of this review is to examine whether these
      changes have resulted in improved perioperative outcomes.

PMID- 17019170
TI  - Bridge therapy to liver transplantation in fulminant hepatic failure.
AB  - The management of patients with fulminant hepatic failure is a major clinical
      endeavor. Early intensive care at an institution able to perform liver
      transplantation is essential. It is recognized that therapy focused solely on
      attempts at preventing/reversing increased intracranial pressure, and the
      treatment of other failing organs as they occur falls well short of ideal. This
      review covers the non-biological and biological techniques utilized in efforts to
      support liver function. The goal is to foster recovery, or to buy enough time for
      successful liver transplantation. Prospective, controlled trials are beginning to
      acknowledge subgroups of fulminant hepatic failure and properly randomize
      therapy. Our understanding of the essential elements of liver support is
      improving, but no single device has yet proved indispensable.

PMID- 17019171
TI  - The preoperative assessment of the cancer patient.
AB  - The cancer patient presents special challenges to the anesthesiologist. Cancer
      may have multiple effects including those due to the primary tumor, metastases,
      the effects and toxicity of cancer therapy, associated paraneoplastic and
      physiologic responses to the tumor and the strong psychological responses
      elicited by cancer. The preoperative evaluation of the cancer patient provides
      opportunities to understand the patient's medical condition and to plan
      management. Specific goals of the preoperative assessment include a relevant and
      complete patient history with emphasis on the cancer, thorough examination of the
      patient, appropriate diagnostic testing and formation of an anesthetic and
      perioperative plan. Patient education and reassurance regarding issues of safety,
      pain control and respect for patient preferences are important goals as well.
      This review provides the anesthesiologist with both general and specific
      information important to the systematic and complete preoperative evaluation of
      the patient with cancer.

PMID- 17019173
TI  - Regional anaesthesia for orthopaedic surgery.
AB  - Recently, there has been considerable interest in regional anaesthetic
      techniques, particularly in peripheral nerve blockade, for orthopaedic limb
      surgery. Many traditional nerve-block techniques have been significantly modified
      to improve their role in both in-patient and out-patient surgery. The
      introduction of long-acting local anaesthetic with a better safety profile as
      well as better equipment for continuous nerve blockade has further increased the
      use of such techniques in the provision of postoperative analgesia. The recent
      developments described in this review are likely to result in wider use of these
      techniques in years to come.

PMID- 17019174
TI  - Novel local anaesthetics and novel indications for local anaesthetics.
AB  - Research into local anaesthetic mechanisms over the past few years has focused on
      two main issues. First, attention has focused on development of compounds with
      fewer side effects, better sensory/motor separation and longer duration of
      action; this has resulted in the introduction of ropivacaine and levobupivacaine
      into clinical practice. These agents have a lesser cardiotoxic effect than older
      compounds, and ropivacaine may in addition offer better sensory/motor separation.
      Several other compounds, including tonicaine and sameridine, are under
      investigation. In addition, the local anaesthetic properties of amitryptiline are
      being studied, and liposome encapsulation of local anaesthetics appears able to
      confer new pharmacokinetic properties on common drugs. Second, the molecular
      basis for several local anaesthetic actions that are not mediated by sodium
      channels has become a topic of interest. The mechanisms that underlie anti
      inflammatory and antithrombotic actions are at present being unravelled. How
      local anaesthetics potentiate antitumour agents, protect neuronal tissue and
      prevent bronchial reactivity is less clear, but the potential clinical benefits
      of these effects deserve further exploration.

PMID- 17019176
TI  - Current world literature.

PMID- 17019175
TI  - Alpha 2 agonists in regional anesthesia and analgesia.
AB  - Clonidine is a partial alpha 2 adrenergic agonist that has a variety of different
      actions including antihypertensive effects as well as the ability to potentiate
      the effects of local anesthetics. It can provide pain relief by an opioid
      independent mechanism. It has been shown to result in the prolongation of the
      sensory blockade and a reduction in the amount or concentration of local
      anesthetic required to produce perioperative analgesia. Different routes for the
      administration of regional anesthesia, including intravenous, intrathecal and
      epidural ones, as well as the addition of clonidine for peripheral neural
      blockade, have been described. It has been also used for intra-articular
      administration. The latest articles describing the use of clonidine in regional
      anesthesia are discussed. Most authors agree that the use of clonidine for
      regional neural blockade in combination with a local anesthetic results in
      increased duration of sensory blockade with no difference in onset time. The
      addition of clonidine to the local anesthetic opioid mixtures seems to produce
      analgesia of longer duration, more rapid onset and higher quality. The higher
      doses of clonidine were associated with a more cephalad spread of the spinal
      blockade and increased sedation and hypertension. When clonidine is added to a
      fentanyl-bupivacaine mixture for epidural labor analgesia, it seems to provide
      satisfactory analgesia of a longer duration than that produced by the fentanyl
      bupivacaine combination alone. Similar results were found when epidural analgesia
      using levobupivacaine with clonidine was used in patients undergoing total hip
      arthroplasty. Less clear results were seen when clonidine was used for caudal
      anesthesia in a pediatric patient population. The addition of clonidine to
      intravenous regional anesthesia resulted in prolongation of the tourniquet time
      and improvement of postoperative analgesia. However, the latter was found to be
      short-lived. In another study, the effects of clonidine used for intra-articular
      administration in combination with morphine were investigated. These authors
      found a significantly higher rate of satisfaction in the group of patients
      receiving clonidine plus morphine. Although several recent studies have shown
      certain benefits from the use of clonidine for regional anesthesia, further
      investigations are necessary to clarify its role.

PMID- 17019177
TI  - Intraoperative transesophageal echocardiography in the new millennium: still
      following the 'dancing doughnut'?

PMID- 17019178
TI  - The influence of genomics on outcome after cardiovascular surgery.
AB  - Recent findings in molecular research suggest that the outcome of cardiovascular
      surgery is at least partly determined by the individual patient's genetic
      predisposition to react to surgical trauma and extracorporal circulation. The
      activation of cellular as well as humoral cascades occurs in the perioperative
      period, and influences the extent of pro- and anticoagulation and pro- and anti
      inflammation. These events contribute to the incidence and severity of
      perioperative ischaemia or organ dysfunction, and thus determine adverse outcomes
      in patients undergoing cardiac surgery. Candidate genes that are possibly
      involved in the development of adverse outcomes not only consist of genes
      relevant to the field of coagulation and inflammation, but also genes functioning
      in lipid metabolism, ion channels, membrane integrity and others. Genomic
      variations may prove to serve as future diagnostic tools for the risk
      stratification of patients undergoing cardiovascular surgery.

PMID- 17019179
TI  - Off-pump coronary artery bypass grafting: new developments but a better outcome?
AB  - Off-pump coronary artery surgery is now performed safely and effectively without
      cardiopulmonary bypass. This review includes indications, approaches, anaesthetic
      and haemodynamic management, and compares the occurrence of postoperative
      complications and multiorgan dysfunction with conventional cardiac surgery.

PMID- 17019180
TI  - Management of the patient with coagulation disorders.
AB  - Understanding normal haemostasis and the pathophysiology of its disorders is
      essential for providing optimal care and ensuring judicious usage of blood
      products, as is keeping abreast of novel therapeutic modalities in a rapidly
      evolving field. The growing availability of synthetic coagulation factors has (at
      least in the western hemisphere) helped to reduce morbidity and therapeutic
      complications, while expanding the indications and usage of these agents.
      Promising advances in gene therapy may indeed introduce a sea change in the next
      decade or two.

PMID- 17019181
TI  - Significance of beta-blockers in the perioperative period.
AB  - Beta-blockers have emerged as one of the key therapeutic agents that can decrease
      cardiac morbidity and mortality. Advances in cardiac beta-adrenergic receptor
      physiology and pharmacology have provided new insights into the beneficial
      effects of beta-blockers in cardiovascular medicine. Although significant
      advances have been made, many specific questions still remain to be answered. We
      will review some of these developments and the current role of beta-blockers in
      peri-operative medicine.

PMID- 17019182
TI  - Vascular stenting.
AB  - An explosion of technology has occurred in the last 10 years, intended to make
      treatment of vascular diseases less invasive. Once the exclusive domain of the
      interventional cardiologist and the coronary circulation, now in 2001 nearly
      every vascular system has been explored as a site for endovascular treatment of
      aneurysmal and atherosclerotic disease. This review will focus on endovascular
      treatment of abdominal aortic aneurysmal disease and carotid artery disease, and
      relevant issues for the anesthesiologist encountering these patients and
      procedures.

PMID- 17019184
TI  - Should smokers stop smoking preoperatively--and if so, when?

PMID- 17019183
TI  - Progress in mechanical ventilation.
AB  - Mechanical ventilation is a life-supporting process employed in the management of
      respiratory failure. Over the years, our understanding of the pathophysiology of
      lung injury has greatly improved, and has aided the technological development of
      ventilatory modes that are more patient 'sensitive' and less traumatizing to the
      lungs. This review will discuss the fundamental modes of mechanical ventilation,
      and present current concepts regarding patient-ventilator interaction that either
      promote lung healing and weaning from positive pressure ventilation or delay
      recovery because of the injudicious use of ventilatory modalities that are
      incapable of meeting the ventilatory demands of the patient on a breath-by-breath
      basis. In addition, the current strategy for mechanical ventilation in acute lung
      injury and acute respiratory distress syndrome will be summarized.

PMID- 17019185
TI  - Capillary pressure-induced lung injury: fact or fiction?
AB  - Lung capillary pressure in healthy humans at rest ranges between 6 and 10 mmHg.
      At maximal effort or in pathophysiological conditions such as left sided heart
      disease or massive pulmonary vasoconstriction, for example in high-altitude
      pulmonary disease, capillary pressure may be markedly elevated. Increased
      capillary pressure directly affects transendothelial fluid dynamics and thus
      results in the formation of hydrostatic lung edema. Excessive pressure increases
      may cause capillary stress failure. Recent studies, however, suggest that the
      microvascular response to lung capillary hypertension is more complex. Pressure,
      strain and shear stress cause dysfunction of the capillary endothelium
      characterized by an imbalanced release of vasoactive mediators. Endothelial
      dysfunction evokes a multicellular response with features of vasoconstriction,
      inflammation, and vascular leakage, thrombosis, and remodeling. These active
      cellular reactions contribute to the pathophysiological process and may be
      specifically targeted by new therapeutic strategies.

PMID- 17019186
TI  - Lung contusion: pathophysiology and management.
AB  - Management of severe pulmonary contusion is a challenge for clinicians. The
      incidence of adult respiratory distress syndrome (5-20%), pneumonia (5-50%), and
      mortality (5-10%) associated with traumatic lung injury has changed little in the
      past three decades. Therapeutic options are limited to basic supportive measures
      such as mechanical ventilation, positive end expiratory pressure, invasive
      cardiopulmonary monitoring, analgesics and aggressive pulmonary hygiene.
      Presently, no pharmacological agents can prevent the progressive respiratory
      embarrassment that is associated with the natural history of the disease, but
      several drugs have been tested in the laboratory. The purpose of this brief
      review is to summarize information published since January 2000 related to the
      clinical management and pathophysiology of lung contusion.

PMID- 17019187
TI  - Methods of lung separation.
AB  - In the last few years, video assisted thoracoscopy, which allows a wide variety
      of diagnostic and therapeutic procedures, has been introduced into clinical
      practice. A growing enthusiasm for minimally invasive surgical approaches and
      improvements in video endoscopic surgical equipment has resulted in the
      widespread use of this technique. Most video assisted thoracoscopy procedures
      require a well-collapsed lung and should only be included in the absolute
      indication for one-lung ventilation. Following placement of a double lumen tube,
      it is the standard of care to check the tube is positioned correctly using
      fiberoptic bronchoscopy. The role of the right-sided double lumen tube is
      discussed in detail in this review. Finally, there are alternatives to the use of
      the double-lumen tube to achieve lung separation, such as the Univent tube or an
      independent bronchial blocker. In many situations the double-lumen tube cannot be
      inserted, due to a difficult airway or at the conclusion of the procedure
      changing the double lumen tube to a single lumen tube may result in loss of
      control over the airway. In such situations, it is essential for the
      anesthesiologists to be familiar with the existing alternatives to the double
      lumen tube.

PMID- 17019188
TI  - Intra-operative use of inhaled vasodilators: are there indications?
AB  - The US Food and Drug Administration and European authorities have recently
      approved inhaled nitric oxide for the treatment of neonates with hypoxic
      respiratory failure associated with pulmonary hypertension. In addition to this
      highly specific condition, there is an increasing 'off-label' use of inhaled
      nitric oxide and other inhaled vasodilators in the perioperative setting.
      Potential indications include right heart failure as a result of acute pulmonary
      hypertension in cardiac and non-cardiac surgery, the prevention of reperfusion
      injury in lung transplantation, the treatment of hypoxaemia during single-lung
      ventilation, and more recently, the treatment of sickle cell crisis.

PMID- 17019189
TI  - Anesthesia for tracheal and endobronchial interventions.
AB  - Tracheal and endobronchial interventions constitute a wide variety of procedures
      offering unique challenges in perioperative airway management and ventilatory
      support. Elective or emergent anesthetic management is individualized according
      to underlying airway pathology, coexisting disease, and patient age. This review
      explores recent literature and reports on relevant advances in anesthetic care.

PMID- 17019190
TI  - Anaesthesia in patients with cystic fibrosis.
AB  - Cystic fibrosis is an autosomal-recessive disorder. In 1989 the gene mutation
      that causes cystic fibrosis was localized on the long arm of chromosome 7. Cystic
      fibrosis occurs in 1/2000 children and the majority now reach adulthood. In view
      of numerous clinical manifestations of cystic fibrosis, these patients frequently
      require surgery. Cystic fibrosis is therefore of increasing interest to
      anaesthesiologists. Preoperative assessment is reviewed. Pre-, intra- and
      postoperative care must be directed toward optimal clearance of viscous
      respiratory secretions, and should minimize the risk of postoperative respiratory
      complications. All procedures should be planned but it is very important to
      prepare patients for surgery, with daily physiotherapy, administration of
      therapeutic agents using aerosols, management of nutrition and pancreatic
      enzymes, and administration of vitamins and antibiotics if indicated. Currently,
      anaesthesia can safely be carried out in cystic fibrosis patients undergoing
      minor surgery, with very low incidence of postoperative respiratory
      complications. Finally, organ transplantation, and in particular lung
      transplantation, with all its attendant anaesthesiological implications, has
      improved the outcome for many patients with cystic fibrosis.

PMID- 17019191
TI  - Treatment with aerosols in mechanically ventilated patients: is it worthwhile?
AB  - Aerosol medications are commonly used in mechanically ventilated patients.
      Several classes of drugs with different properties and indications may be given
      by inhalation. In all cases, compared with the systemic route, the inhaled
      therapy has the main advantage that for a given therapeutic response, the drug
      dose is several-fold lower, while the systemic absorption is negligible, thus the
      side effects are greatly minimized. In addition, for some medications the
      systemic route either causes non-acceptable side effects or results in
      considerably inferior therapeutic response, rendering the inhaled route the
      method of choice of drug administration. Bronchodilators, corticosteroids,
      vasoactive drugs, surfactants, antibiotics, helium and perfluorocarbons are the
      medications that can be given by inhalation during mechanical ventilation. Some
      of those represent part of the standard treatment for various groups of
      mechanically ventilated patients, while the role of others has not been well
      established yet.

PMID- 17019192
TI  - Current world literature.

PMID- 17019193
TI  - Ischemia reperfusion injury, preconditioning and critical illness.
AB  - The purpose of this review is to describe in more detail ischemia reperfusion
      injury and preconditioning, and to speculate on the potential role of
      preconditioning in the care of critically ill patients. Current hemodynamic
      treatment of hypotension and hypoperfusion in critically ill patients is directed
      at ensuring essential organ perfusion by maintaining intravascular volume and
      cardiac output, and ensuring adequate oxygen delivery by maintaining arterial
      oxygen partial pressure and hemoglobin levels. However, morbidity and mortality
      remain high and new approaches to critically ill patients are required.
      Treatments are needed that can protect against organ ischemia during periods of
      low blood flow. In recent years, there has been a growing appreciation of the
      importance of ischemia reperfusion injury. Ischemia associated with reperfusion
      may result in greater injury than ischemia alone. Ischemic preconditioning is
      used to describe the protective effect of short periods of ischemia to an organ
      or tissue against longer periods of ischemia. Although first described in the
      myocardium, there is now evidence that this phenomenon occurs in a wide variety
      of organs and tissues, including the brain and other nervous tissue such as the
      retina and spinal cord, liver, stomach, intestines, kidney, and the lungs.
      Preconditioning therapy may offer a new avenue of treatment in critically ill
      patients. Both traditional preconditioning methods and pharmacologic agents that
      mimic or induce such preconditioning may be used in the future. Clinical trials
      of pharmacologic agents are underway in patients with coronary artery disease.
      Further trials of such methods and agents are needed in critically ill patients
      suffering from sepsis or multiorgan system failure.

PMID- 17019194
TI  - Intensive care unit errors: detection and reporting to improve outcomes.
AB  - Most efforts to identify and investigate errors in medicine have focused on
      active failures and general provider behaviors. We believe that the greatest
      improvements in error identification and management in the intensive care unit
      will be achieved by focusing on the intensive care unit's organizational
      characteristics. The results of three recent studies suggest that differences in
      intensive care unit organizational characteristics are significantly related to
      variation in the risk-adjusted morbidity and mortality. Physicians must assume
      greater leadership in creation of these safe systems for intensive care patients.
      We encourage the creation of multi-institutional communities to work
      collaboratively to advance patient safety in high-risk environments like the
      intensive care unit.

PMID- 17019195
TI  - Ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is the most serious infectious complication in
      critically ill patients, associated with increased length of intensive care unit
      treatment and high mortality rates. Investigations focused on outcome variables
      have improved the database to estimate diagnostic and therapeutic management
      strategies. This knowledge has diminished the importance of the discussion on how
      to diagnose the pneumonia. This review summarizes recent data on epidemiology and
      mortality, risk factors and prevention, diagnosis, microbiology and antimicrobial
      treatment of ventilator-associated pneumonia.

PMID- 17019196
TI  - High-frequency oscillatory ventilation in infants and children.
AB  - The goal of mechanical ventilation in patients with acute lung injury is to
      support gas exchange and mitigate ventilator-associated lung injury. High
      frequency oscillatory ventilation relies on the generation of a constant
      distending pressure, small tidal volumes and rapid respiratory rates with the
      intent to recruit atelectatic lung, reduce peak inflating pressures and limit
      volutrauma. The utilization of high-frequency oscillatory ventilation has
      dramatically increased in neonatal and pediatric intensive care units. As there
      is an overlap between the intensive care unit and the operating room,
      anesthesiologists must be familiar with recent advances in the care of infants
      and children with acute respiratory failure. High-frequency oscillatory
      ventilation has been used successfully to manage patients with severe respiratory
      failure who have failed conventional mechanical ventilation. When initiated
      early, high-frequency oscillatory ventilation has been shown to improve
      oxygenation and reduce acute and chronic lung injury in neonates, infants and
      children. Further trials are necessary to better delineate the benefits and risks
      of this therapy in various patient populations.

PMID- 17019197
TI  - Resuscitation for major trauma.
AB  - Disability from traumatic injury is on the increase worldwide. Dogma rather than
      scientific evidence has tended to be responsible for determining the treatment of
      major trauma victims. Evidence is now beginning to emerge, however, questioning
      the dogma, and suggesting that different treatment options may yield better
      outcomes. This review examines the recent literature in resuscitation for major
      trauma.

PMID- 17019198
TI  - Fluid resuscitation of the patient with major trauma.
AB  - Current reviews and consensus documents now recommend a more discriminating
      approach to the traditional practices of delivering liberal infusions of
      intravenous fluid to all major trauma patients with suspected or known major
      hemorrhage. The evolving evidence suggests that aggressive fluid resuscitation
      prior to hemostasis leads to additional bleeding through hydraulic acceleration
      of hemorrhage, soft clot dissolution, and dilution of clotting factors.
      Aggressive preoperative fluid infusion is still considered appropriate for
      unconscious patients without palpable blood pressure or for those with
      controllable hemorrhage (e.g. isolated extremity or head injury), However, the
      latest recommendations are to limit or delay intravenous fluid resuscitation
      preoperatively in those with uncontrollable hemorrhage (e.g. those with
      penetrating torso injuries), even if they are hypo-perfusing. Although most
      clinicians still generally support fluid resuscitation for multisystem blunt
      trauma, particularly with head injury, the most recent experimental data have
      begun to challenge this traditional practice as well, suggesting a 'slow
      infusion' approach when there is risk for uncontrolled internal bleeding. By
      providing oxygen delivery with slow, limited infusion, new hemoglobin-based
      oxygen carriers might help to resolve the current dilemma of having to limit
      preoperative resuscitation when there is risk of uncontrolled hemorrhage.

PMID- 17019199
TI  - To transfuse or not in trauma patients: a presentation of the evidence and
      rationale.
AB  - The administration of allogeneic red blood cell transfusions to the trauma
      patient is an essential and potentially life-saving component of trauma care. The
      big question is when to transfuse, and how much? In this review, we explore the
      evidence and provide rationales for current and future red blood cell transfusion
      strategies in the trauma patient. We also discuss the changing trends and
      competing risks associated with transfusions as well as current evidence for
      different blood conservation strategies in the context of trauma.

PMID- 17019200
TI  - Pediatric trauma anesthesia.
AB  - Trauma has a significant impact on pediatric morbidity and mortality. Depending
      on the emergency medical services and health care system, anesthesiologists may
      be involved in pediatric trauma care at the scene, in the emergency department,
      in the operating room, or in the intensive care unit. Familiarity with the
      pathophysiology of pediatric trauma and age-dependent anatomical and
      physiological features is, therefore, essential to every anesthesiologist. Fast
      and appropriate interventions with respect to the clinical status and the
      suspected injuries are the key to successful treatment. Due to the high incidence
      of head injury, airway management and hemodynamic stabilization are of utmost
      importance. For preclinical trauma care, however, evidence-based data showing a
      gold standard for pediatric trauma care are still lacking.

PMID- 17019201
TI  - Cervical spine injury and airway management.
AB  - Cervical spine injuries occur in 2-5% of blunt trauma patients, and 1-5% of these
      injuries are initially missed. Data from the large National Emergency X
      Radiography Utilisation Study have helped to define the problem in some detail.
      There is a consensus on how to clear the cervical spine in patients who are
      alert, but in patients with altered mental status the choice of strategy for
      spinal clearance is more controversial. Despite obtaining extensive radiological
      studies, some clinicians will not clear the patient's cervical spine until full
      recovery of consciousness. As long as manual in-line neck stabilization is
      applied, rapid sequence induction of anaesthesia, followed by direct laryngoscopy
      and oral intubation appears to be safe in the patient with a cervical spine
      injury. If intubation is not urgent, an awake fibreoptic technique is a useful
      option. If intubation of the patient with a potential cervical spine injury
      fails, or appropriate experienced personnel are unavailable, the laryngeal mask
      airway or one of its various modifications are useful alternatives.

PMID- 17019202
TI  - Suspended animation for delayed resuscitation.
AB  - 'Suspended animation for delayed resuscitation' is a new concept for attempting
      resuscitation from cardiac arrest of patients who currently (totally or
      temporarily) cannot be resuscitated, such as traumatic exsanguination cardiac
      arrest. Suspended animation means preservation of the viability of brain and
      organism during cardiac arrest, until restoration of stable spontaneous
      circulation or prolonged artificial circulation is possible. Suspended animation
      for exsanguination cardiac arrest of trauma victims would have to be induced
      within the critical first 5 min after the start of cardiac arrest no-flow, to buy
      time for transport and resuscitative surgery (hemostasis) performed during no
      flow. Cardiac arrest is then reversed with all-out resuscitation, usually
      requiring cardiopulmonary bypass. Suspended animation has been explored and
      documented as effective in dogs in terms of long-term survival without brain
      damage after very prolonged cardiac arrest. In the 1990s, the Pittsburgh group
      achieved survival without brain damage in dogs after cardiac arrest of up to 90
      min no-flow at brain (tympanic) temperature of 10 degrees C, with functionally
      and histologically normal brains. These studies used emergency cardiopulmonary
      bypass with heat exchanger or a single hypothermic saline flush into the aorta,
      which proved superior to pharmacologic strategies. For the large number of
      normovolemic sudden cardiac death victims, which currently cannot be
      resuscitated, more research in large animals is needed.

PMID- 17019203
TI  - Interhospital transport: transport of critically ill patients.
AB  - Primary emergency medicine systems in developed countries are well organized.
      Besides this primary system a secondary interhospital transport system has been
      developed in the past decade. The need for this system is expected to increase in
      the future following dramatic changes in the organization of the medical health
      system. This article outlines the current status of these secondary interhospital
      transfer systems, their components, possibilities, advantages or disadvantages,
      and the actual literature. Surprisingly, the available scientific data on these
      cost-intensive and highly developed systems are quite insufficient.

PMID- 17019205
TI  - Public demand for greater safety: what solutions can be proposed?

PMID- 17019204
TI  - Coagulation management in trauma patients.
AB  - Hemorrhage after traumatic injury results in coagulopathy which only worsens the
      situation. This coagulopathy is caused by depletion and dilution of clotting
      factors and platelets, increased fibrinolytic activity, hypothermia, metabolic
      changes and anemia. The effect of synthetic colloids in compensating the blood
      loss further aggravates the situation. Bedside coagulation monitoring permits
      relevant impairment of the coagulation system to be detected very early and the
      efficacy of the hemostatic therapy to be controlled directly. Administration of
      fresh frozen plasma, platelet concentrations, clotting factors and probably
      antifibrinolytic agents is essential in restoring the impaired coagulation system
      in trauma patients.

PMID- 17019206
TI  - Cost considerations in the use of anaesthetic drugs.
AB  - Measuring the direct drug costs of an anaesthetic is relatively easy, but
      assessing increased expenditure in relation to clinical benefits and indirect
      costs is not. This review examines a number of papers that have attempted just
      such a task and tries to illustrate some of the difficulties inherent in this
      important area of cost-effective analyses.

PMID- 17019207
TI  - Economics of antiemetics.
AB  - Numerous studies about postoperative nausea and vomiting management are available
      and meta-analyses have helped to define the appropriate doses of the effective
      drugs. Almost all recent papers include some economical considerations. In order
      to rationalize the therapeutic protocols, strategies including systematic
      prophylaxis, treatment of established postoperative nausea and vomiting only,
      targeted prophylaxis, treatment combinations aimed at secondary prophylaxis, and
      global management have all been proposed. Published data are not always valid for
      every clinical setting and a cost-effective policy needs an evaluation effort
      from the local care providers (incidence of immediate and delayed postoperative
      nausea and vomiting, cost of an emetic episode, indirect impact of postoperative
      nausea and vomiting). This is the only way to avoid improper use of conclusions
      possibly drawn in totally different medical and economical circumstances.
      Patients consider postoperative nausea and vomiting as the worst postoperative
      symptom. This translates into the sizeable amount of money patients are willing
      to pay in order to avoid this major side effect.

PMID- 17019208
TI  - Indicators of anesthesia safety and quality.
AB  - In 1999, the Institute of Medicine shocked the world by claiming that medical
      error was among the leading causes of death in the United States. In contrast,
      anesthesiology was cited as an area in which there have been impressive gains in
      safety and quality. The mechanisms to which these impressive gains have been
      attributed include practice guidelines, anesthesia simulators, and benchmarking.
      Unfortunately, the current literature offers little evidence that these
      systematic approaches to patient safety have resulted in measurable improvements
      in quality, but efforts continue in the development of traditional and non
      traditional quality indicators.

PMID- 17019209
TI  - Risk factors for prolonged stay after ambulatory surgery: economic
      considerations.
AB  - The risk factors that prolong length of stay of ambulatory patients can be
      classified as preoperative, intraoperative, and postoperative. Preoperative
      factors include the type of surgery, ear, nose and throat and strabismus surgery,
      old age and pre-existing congestive heart failure. Intraoperative factors include
      increasing length of surgery, and general anesthesia, while postoperative factors
      include postoperative nausea and vomiting, excessive pain and adverse
      cardiovascular events. The factors that anesthesiologists can address to reduce
      length of stay are postoperative nausea and vomiting and excessive pain.
      Multimodal management of postoperative nausea and vomiting and pain can minimize
      adverse events and thereby reduce length of stay in the postanesthetic care unit,
      but will not necessarily lead to a reduction in staffing levels. As personnel
      costs contribute the majority of postanesthetic care unit costs, more than 95%,
      direct financial savings may not be possible from eliminating adverse events
      alone. Optimizing the use of the postanesthetic care unit and reducing total
      hours in the unit with higher operating room turnover may lead to indirect
      financial benefits.

PMID- 17019210
TI  - Communication with patients before anesthesia and obtention of preanesthetic
      consent.
AB  - Communication in medicine deserves greater attention than it usually receives.
      The physician's obligation to obtain informed consent for clinical care and
      research forces the issue out into the open. Recognition that communication can
      have legal and economic impacts suggests communication skills should be
      cultivated as a medical art. This review places communication issues in
      anesthesia practice, especially those related to informed consent, in an
      historical, and when possible, scientific context.

PMID- 17019212
TI  - Current world literature.

PMID- 17019211
TI  - Economic aspects of an anesthesia preoperative evaluation clinic.
AB  - Studies continue to demonstrate that preoperative evaluation clinics help to
      prepare patients for surgery in a manner that minimizes cost and optimizes
      outcomes. These clinics are becoming common in both teaching and community
      hospitals. Many full service preoperative assessment clinics utilize specially
      trained nurses who are under the direction of an anesthesiologist. These clinics
      are associated with favorable outcomes, dramatic decreases in preoperative
      testing, infrequent subspecialty consultation and shorter lengths of stay. The
      current literature is reviewed and organizational and clinical changes that
      improve efficiency and patient care are highlighted.

PMID- 17019213
TI  - Only anesthesiologists should provide epidural labor analgesia.

PMID- 17019214
TI  - The pregnant cardiac woman.
AB  - Cardiac diseases are present in 0.5-4% of pregnancies, and they remain a frequent
      cause of death during pregnancy. Pregnancy per se imposes significant hemodynamic
      changes, placing a major burden on the cardiovascular system. The early
      recognition and close follow-up of patients with cardiac diseases will improve
      maternal tolerance to the cardiovascular burden imposed by pregnancy, promote
      fetal growth and neonatal survival. Rheumatic heart disease remains the most
      frequent heart disease in the pregnant population with pulmonary edema as the
      most frequent complication. Atrial septal defect is the most frequent congenital
      heart disease in the adult population, whereas tetralogy of Fallot is the most
      common cyanotic congenital heart disease. An improvement in modern techniques of
      monitoring, a better understanding of the pathophysiology of cardiac disease, as
      well as multidisciplinary care has led to a substantial improvement in outcome of
      the pregnant cardiac patient. Management should be initiated before conception as
      it will provide optimal clinical conditions and sufficient information on the
      underlying pathophysiology.

PMID- 17019215
TI  - Anaesthesia for non-scheduled caesarean delivery.
AB  - In many countries there has been an increase in the number of women who deliver
      by caesarean section. This article reviews anaesthetic management of non
      scheduled caesarean section. The choice of anaesthetic technique (regional
      anaesthesia versus general anaesthesia) is discussed and highlighted particularly
      from the viewpoint of urgency of operative delivery. A multidisciplinary approach
      is mandatory especially in emergency cases to prevent morbidity and mortality in
      mothers and neonates.

PMID- 17019216
TI  - Neuraxial opioids for labour analgesia: analgesic efficiency and effect on
      labour.
AB  - Neuraxial opioids have changed the practice of obstetric anaesthesia and
      analgesia dramatically. Excellent analgesia with minimal side effects started an
      era of ever increasing numbers of women who opt for the 'painless birth
      experience'. Several papers have been reported during 2001 that examine analgesic
      efficacy, maternal side effects, and effect on foetal well-being of epidural and
      spinal opioids. Foetal bradycardia following intrathecal opioid analgesia, an
      increasingly popular technique, has attracted particular attention over the past
      few years. The present review addresses recently reported work that, according to
      the author, is key to this field.

PMID- 17019217
TI  - The future of paediatric anaesthesia is total intravenous anaesthesia.

PMID- 17019218
TI  - Clonidine in paediatric anaesthesia.
AB  - PURPOSE OF REVIEW: This review aims to summarize results of recently published
      studies concerning clonidine application in paediatric anaesthesia, to analyse
      trends in these studies, and to discuss perspectives of the perioperative use of
      clonidine for children. RECENT FINDINGS: Reassessment of clonidine premedication
      has revealed that oral clonidine is inferior to midazolam for preoperative
      sedation. Oral or intravenous clonidine has been successfully used for the
      prevention of sevoflurane-induced agitation during emergence from anaesthesia.
      Peripheral injection or caudal (epidural) administration of clonidine prolonged
      the duration and enhanced the quality of postoperative analgesia by local
      anaesthetics without severe side effects. However, some negative results
      concerning potentiation of postoperative analgesia with clonidine have been
      reported. SUMMARY: Clonidine may be less favored than midazolam as premedication
      for children because of inferior clonidine-induced sedation. Additional
      comparative studies are required, however, to confirm this finding. On the other
      hand, clonidine-induced analgesia may well be useful and find wide application in
      paediatric anaesthesia. Prospective multicentre trials using a larger number of
      patients will be needed to verify the usefulness of caudal clonidine for
      postoperative pain relief. Prophylactic use of clonidine against sevoflurane
      induced agitation may represent a new and promising application. Assessment of
      the efficacy of clonidine in potentiating regional anaesthesia/analgesia by local
      anaesthetics in children also needs more investigation. Moreover, it may be
      worthwhile to try new successful applications demonstrated in adults for
      paediatric anaesthesia.

PMID- 17019219
TI  - Upper airway infection and pediatric anesthesia: how is the evidence based?
AB  - Anesthesia for the child with an upper respiratory infection remains one of the
      most common, yet contentious, issues facing the pediatric anesthesiologist. A
      general lack of evidence-based research has led to disparities in the manner in
      which children with upper respiratory infections have been traditionally managed.
      More recent research, however, suggests that children with uncomplicated
      infections can be managed safely, given that most complications can be
      anticipated, recognized, and treated. This review summarizes the evolving
      literature regarding cancellation of surgery for the child with an upper
      respiratory infection, perioperative outcomes, and anesthetic management.

PMID- 17019220
TI  - Aspiration in pediatric anesthesia: is there a higher incidence compared with
      adults?
AB  - PURPOSE OF REVIEW: Recent data in both adults and children have suggested that
      the incidence and severity of the pulmonary aspiration of gastric contents has
      declined. Previous studies have indicated that aspiration is more common in
      children than in adults. This review will examine the available data to compare
      the incidence and severity of aspiration in adults and children. RECENT FINDINGS:
      There are several studies, some of which have been published recently, that have
      provided an epidemiologic perspective on the problem of aspiration. SUMMARY:
      Based on the available data, aspiration appears to be slightly more common in
      children than in adults. The difference, however, is less than that previously
      reported. Morbidity associated with aspiration is rare in all age groups. This is
      especially true for children.

PMID- 17019221
TI  - Management of the paediatric airway: new developments.
AB  - During the last 2 years, some interesting new devices have been made available to
      improve airway management in children and infants, and several studies have
      advanced our understanding concerning risks and benefits of the current practice
      in the field. Certain risk factors for airway related problems during anaesthesia
      in children having a cold have been identified, and new aspects of the
      controversy concerning the use of cuffed endotracheal tubes in children
      presented. Novel video-assisted systems have been introduced for the management
      of the difficult airway in paediatric patients, and new applications for well
      known devices have been suggested, such as the laryngeal mask airway serving as
      guidance for fibreoptic intubation. Recent studies also demonstrated specific
      problems with the laryngeal mask airway in infants, as well as the advantages of
      a new prototypic laryngeal mask airway for children, similar to the ProSeal (LMA
      International S.A. Group, USA). Furthermore, the following review presents new
      data about the use of the cuffed oropharyngeal airway, the laryngeal tube, and
      the Arndt bronchus blocker in paediatric patients.

PMID- 17019222
TI  - The propofol infusion syndrome in infants and children: can we predict the risk?
AB  - Propofol has been an immensely successful anaesthetic induction agent but there
      is an increasing number of reports of serious complications when it has been used
      as an infusion to provide sedation for prolonged periods. The first reports
      involved children who died from intractable myocardial failure preceded by a
      metabolic acidosis, lipaemic plasma, fatty infiltration of the liver and evidence
      of muscle damage. As more cases have been reported the association between
      propofol and the syndrome has become more certain. Recently adult cases have
      appeared and a metabolic explanation has been suggested. The syndrome has a high
      mortality and the only effective treatment appears to be dialysis.

PMID- 17019223
TI  - The caudal catheter in neonates: where are the restrictions?
AB  - PURPOSE OF REVIEW: In neonates, epidural catheters inserted at the sacral hiatus
      can easily be advanced to a lumbar or thoracic level. These 'caudal catheters'
      are popular because they allow the neonate to benefit from epidural analgesia
      without the concerns of spinal cord injury potentially associated with primary
      thoracic placement in an asleep neonate. This review looks at use and benefits,
      and risks and complications of caudal epidural catheters in neonates. RECENT
      FINDINGS: Restrictions of neonatal caudal catheters are related to risks
      associated with placement and advancement of the catheters, infectious risks of
      caudal catheters, and toxicity risks related to the higher free fraction and
      lower clearance of bupivacaine in neonates. Caudal catheters in neonates are
      popular, but evidence that they improve outcome is lacking. SUMMARY: Epidural
      anesthesia and analgesia for neonates should be performed and managed by
      pediatric anesthesiologists. Potential risks and complications must be
      appreciated and all steps to maximize safety of the technique must be taken. In
      particular, close postoperative observation and pain service management are
      indispensable. Future research should investigate the risks of caudal and
      segmentally placed catheters in neonates, study the role of epidural analgesia in
      outcome improvement for neonates, and guide us to safer use of local anesthetics
      suitable for neonates with their pharmacologic immaturity.

PMID- 17019224
TI  - Anesthesia and informed consent.

PMID- 17019225
TI  - Anesthesia for patients with diabetes mellitus.
AB  - PURPOSE OF REVIEW: Diabetes mellitus has diverse effects on all organ systems of
      the body. Insulin physiology and metabolic control are far more complex than
      previously thought. Research continues to reveal more information about the
      central role of insulin in metabolism. The treatment of hypertension and
      nephropathy as well as hyperglycemia in patients with diabetes has emerged as
      being critical for prevention of long-term diabetic complications. The issue of
      primary importance to the anesthesiologist is whether strict glycemic and
      hemodynamic control during the perioperative period affect outcome. RECENT
      FINDINGS: Maintenance of euglycemia and physiologic control of insulin responses
      to changes in glucose levels have been shown to prolong life and reduce
      complications from diabetes mellitus. The identification and treatment of
      prediabetic patients may significantly delay the onset of overt diabetes.
      Perioperative control of glucose has become tighter, but the optimum level of
      glucose and ideal method of insulin delivery during surgery remain controversial.
      Perioperative control of blood pressure and vascular responses may be as
      important as glucose control for prevention of adverse perioperative events.
      SUMMARY: Tight long-term control of glucose and blood pressure improve outcome in
      patients with diabetes. The same philosophy of management is being applied to the
      perioperative period. Routine measurement of intraoperative blood glucose levels
      and appropriate insulin administration are now standard practice, but the ideal
      regimen for insulin administration remains to be determined.

PMID- 17019226
TI  - Anesthesia and renal disease.
AB  - PURPOSE OF REVIEW: To present and interpret the relevant research (Jan 2001-Feb
      2002) which has the most important implications for clinical anesthesiology as
      regards the prevention of perioperative renal dysfunction and the anesthetic
      management of patients with renal disease. RECENT FINDINGS: Prolonged sevoflurane
      anesthesia with fresh gas flow less than 1 l min is unlikely to lead to
      clinically significant renal injury. When used as maintenance agents for patients
      undergoing coronary artery bypass grafting, sevoflurane anesthesia at a fresh gas
      flow of 3 l min, isoflurane and propofol are associated with similar rates of
      postoperative renal dysfunction. Less compound A is produced with smaller soda
      lime containers. High flow sevoflurane anesthesia (fresh gas flow of 4-6 l min)
      in combination with perioperative ketorolac is unlikely to lead to renal injury.
      Chronic treatment with angiotensin-converting enzyme inhibitors is associated
      with an increased incidence of postoperative renal impairment in patients
      undergoing elective aortic surgery. Thoracic epidural anesthesia and
      postoperative analgesia are associated with a decreased incidence of renal
      failure in patients undergoing coronary artery bypass grafting. Compared with
      open surgical repair, endovascular repair of aortic aneurysm is associated with
      less renal injury. SUMMARY: Sevoflurane anesthesia at low or high fresh gas flow
      rates is probably no more injurious to the kidneys than other commonly used
      maintenance agents. Chronic angiotensin-converting enzyme inhibition may increase
      perioperative renal dysfunction. The use of thoracic epidural anesthesia and
      analgesia may reduce the incidence of postoperative renal failure.

PMID- 17019227
TI  - Multiple sclerosis and anesthetic implications.
AB  - PURPOSE OF REVIEW: Multiple sclerosis remains prevalent among young women in the
      United States of America. It is a disease of the central nervous system that
      possesses many anesthetic implications. Anesthesia providers need to understand
      this disorder and its multiple anesthetic ramifications. RECENT FINDINGS: Recent
      work has provided more insight into the etiology of multiple sclerosis, its
      pathogenesis, diagnosis and natural history. A number of new medications have
      also been added to the therapeutic armamentarium. Optimal anesthetic care entails
      a thorough preoperative evaluation, medication history and neurologic
      examination, intraoperative awareness of conditions that may precipitate attacks
      and lead to potentially life-threatening complications, as well as postoperative
      attention to respiratory and other risks. Recommendations for management are
      based on information from small retrospective studies and anecdotal reports.
      SUMMARY: In summary, our aim is to provide an updated view of multiple sclerosis
      from the perspective of perioperative care, emphasizing interactions between the
      disease, surgery and anesthesia.

PMID- 17019228
TI  - Anesthesia and myopathy.
AB  - PURPOSE OF REVIEW: This report reviews the derangements of neuromuscular
      transmission in the different types of myopathy. RECENT FINDINGS: The article
      covers recent literature on myopathy, whether prejunctional, junctional or
      postjunctional, as well as intensive care unit myopathy, and outlines the
      influence of myopathy on the action of both depolarizing and non-depolarizing
      muscle relaxants. SUMMARY: The review classifies myopathy according to its cause,
      and sheds light on the upregulation and downregulation of endplate acetylcholine
      receptors. These findings are important for both clinical practice, and for
      research into neuromuscular transmission.

PMID- 17019230
TI  - Current world literature.

PMID- 17019229
TI  - Corticosteroids and anesthesia.
AB  - PURPOSE OF REVIEW: For decades, anesthesiologists and surgeons have
      prophylactically provided 'stress steroids' to patients with presumed
      adrenocortical suppression. Other indications for glucocorticoids have included
      the suppression of cerebral or airway edema, the inhibition of systemic
      inflammatory responses to cardiopulmonary bypass, and the treatment of shock
      states possibly associated with adrenocortical insufficiency. Some recent studies
      have either restated or challenged the conventional supraphysiological doses of
      'stress steroids', while others have investigated the efficacy of glucocorticoids
      in improving various aspects of postoperative recovery. RECENT FINDINGS: In 2001,
      Jabbour summarized the normative rationale and dose regimen for stress-dose
      steroids in patients who have been receiving corticosteroids. A few months later,
      Brown and Buie concluded from their literature review that such patients can be
      safely managed with only physiologic or maintenance glucocorticoid
      administration. A torrent of reports on the antiemetic effects of dexamethasone
      generally indicate that this drug does reduce the incidence of postoperative
      nausea and vomiting, with somewhat delayed but prolonged efficacy, and acts
      synergistically with 5-HT3 receptor antagonists. Other authors have studied the
      administration of corticosteroids to patients undergoing major abdominal and
      other operations, and have found beneficial effects on various complications.
      SUMMARY: While the conventional practice concerning 'stress steroids' is probably
      harmless and possibly beneficial, similar benefits might be seen with lower
      prophylactic doses. Alternatively, new uses for these old agents are arising, and
      may enable us to improve the convalescence of larger numbers of our patients.

PMID- 17019231
TI  - Determinants of drug onset.
AB  - PURPOSE OF REVIEW: The timing and magnitude of drug onset can be influenced by
      factors in the chain of drug delivery from the site of administration to the site
      of effect. This review examines recent evidence regarding the contribution and
      significance of these factors. RECENT FINDINGS: It is apparent that drug
      formulations and mixtures can play a significant role in drug onset. An extension
      of this is the effect of coadministration of drugs, which can influence drug
      effect both by altering the physiology underlying drug delivery and by an effect
      at the target organ. Of the physiological variables, cardiac output and its
      distribution are clearly important. Cardiac output is a significant source of
      variability in drug response, and indeed has been successfully incorporated into
      pharmacokinetic models. The pattern of cardiac output distribution is also
      relevant. In particular, the blood flow to target organs will influence both the
      timing and magnitude of the effect of some anaesthetic drugs. In addition, the
      role of the lung in affecting drug distribution may be important for some drugs.
      At the site or organ of effect itself, variability in drug distribution, drug
      receptor interactions, and the influence of other drugs, can all impact on the
      profile of drug onset. SUMMARY: Factors in the chain of drug delivery have been
      demonstrated to affect the nature of drug onset, and can account for some of the
      observed variability in response. The significance to dosing guidelines and
      strategies, and to predictions of variability in response, remains to be
      explored.

PMID- 17019232
TI  - Measurement and monitoring of neuromuscular blockade.
AB  - PURPOSE OF REVIEW: For more than three decades, 'experts' in the clinical
      pharmacology of neuromuscular blocking agents have advocated routine
      intraoperative use of peripheral nerve stimulators as monitors of neuromuscular
      function. This advice is far from universally honored in practice. In part, this
      dichotomy between 'accepted wisdom' and actual day-to-day practice may stem from
      a failure to provide the clinician with a peripheral nerve stimulator that does
      not require subjective evaluation of evoked responses. For 99% of anesthetists,
      the train-of-four fade ratio is a parameter that they read about but cannot
      measure. This need no longer be the case. RECENT FINDINGS: Small battery operated
      units are now available that are relatively inexpensive, easy to set up, and
      provide objective measurement of the train-of-four ratio. Although agreement
      between the output of these acceleromyographic and piezoelectric sensors with
      such 'gold standard' technologies as mechanomyography and electromyography is not
      absolute, it is probably adequate for clinical case management. SUMMARY: It is my
      hope (and I have no financial interest in any of the cited devices) that the
      present review will encourage further distribution of objective monitors of
      neuromuscular function.

PMID- 17019233
TI  - Closed-loop control of anaesthesia.
AB  - PURPOSE OF REVIEW: Closed-loop systems are able to make decisions on their own
      and try to reach and maintain a preset target. As a result, they might help the
      anaesthesiologist in optimizing the titration of drug administration without
      overshooting, controlling physiological functions and guiding monitoring
      variables. Thanks to the development of fast computer technology and more
      reliable pharmacological effect measures, the study of automation in anaesthesia
      has regained popularity. RECENT FINDINGS: This short review focuses on the most
      recently developed and tested feed-back systems in anaesthesia. Various new
      approaches for controlling the administration of intravenous and inhaled hypnotic
      anaesthetic drugs have been published recently. For analgesics, a framework for
      further research has been presented in the literature. For other drugs, such as
      muscle relaxants and haemodynamics, a short review can be found. SUMMARY: Until
      now, most of these systems are still under development. The challenge is now to
      establish fully the safety, efficacy, reliability and utility of closed-loop
      anaesthesia for its adoption into the clinical setting. Besides the optimization
      of controlled variables and control models, these systems have to be tested in
      extreme circumstances.

PMID- 17019234
TI  - Mechanisms of general anesthesia.
AB  - PURPOSE OF REVIEW: Anesthetics influence a wide variety of transmitter- and
      voltage-gated ion channels in the mammalian central nervous system. At the
      molecular level, the gamma-aminobutyric acid (GABA) subtype A receptor has
      emerged as a primary therapeutic target. This review highlights recent advances
      in our understanding of how anesthetics modify GABA(A) receptor function. RECENT
      FINDINGS: Anesthetics bind to discrete selective binding sites on GABA(A)
      receptors--a discovery that challenges lipid-based theories of anesthesia. Not
      all GABA(A) receptors are equally sensitive to anesthetics because positive
      allosteric modulation is critically dependent on receptor subunit composition.
      Moreover, GABA(A) receptors located in extrasynaptic regions of hippocampal
      neurons display a greater sensitivity to propofol and benzodiazepines than do
      receptors located in subsynaptic regions. Enhancement in GABAergic inhibition may
      not account for all of the behavioral end-points associated with the anesthetic
      state. In particular, the immobilizing properties of anesthetics may not be
      solely mediated by GABA(A) receptors. Finally, synthetic neurosteroids are being
      developed as improved general anesthetics. SUMMARY: Detailed insights into
      anesthetic-GABA(A) receptor interactions have resulted in intense efforts to
      develop safer drugs that selectively target subtypes of GABA(A) receptors.

PMID- 17019235
TI  - Current status of preemptive analgesia.
AB  - PURPOSE OF REVIEW: The controversy over preemptive analgesia continues unabated,
      with studies both supporting and refuting its efficacy. The timing of an
      analgesic intervention and presence of a placebo control may have significant
      impact on the interpretation of results and may have led to the premature
      conclusion that preemptive analgesia is of limited clinical utility. A review of
      the recent literature using strict definitions of preemptive and preventive
      analgesia is required in order to clarify the broader issue of the benefits of
      perioperative analgesia. RECENT FINDINGS: A total of 27 studies, published from
      April 2001 to April 2002, were found to evaluate preemptive (n = 12) or
      preventive analgesia (n = 15). Evidence for a benefit of preventive analgesia was
      strong, with 60% of studies finding reduced pain or analgesic consumption beyond
      the clinical duration of action of the analgesic intervention. Evidence for a
      benefit of preemptive analgesia was equivocal, with 41.7% of studies
      demonstrating that preincisional treatment reduces pain or analgesic consumption
      to a greater extent than does postincisional treatment. SUMMARY: Studies that
      used a preventive design had a greater likelihood of finding a beneficial effect.
      The application of preventive perioperative analgesia (not necessarily
      preincisional) is associated with a significant reduction in pain beyond the
      clinical duration of action of the analgesic agent, in particular for the N
      methyl-D-aspartate antagonists. The classical definition of preemptive analgesia
      should be abandoned in favor of preventive analgesia. This will broaden the scope
      of inquiry from a narrow focus on preincisional versus postincisional
      interventions to one that aims to minimize postoperative pain and analgesic
      requirements by reducing peripheral and central sensitization arising from
      noxious preoperative, intraoperative and postoperative inputs.

PMID- 17019236
TI  - Magnetic resonance imaging anesthesia: new challenges and techniques.
AB  - PURPOSE OF REVIEW: The increasing use of magnetic resonance imaging as a
      diagnostic modality has led to increased demand for sedation and monitoring
      during the procedure. This review is to acquaint the reader with the most recent
      developments in magnetic resonance imaging diagnostics and to describe the
      evolving techniques and strategies for patient management. RECENT FINDINGS: Many
      centers are meeting the challenges of increasing demand by streamlining their
      sedation/anesthetic protocols to achieve greater efficiency. Some have enlisted
      the help of nursing staff who are trained to provide sedation for certain
      patients. Continued experience in magnetic resonance imaging anesthesia has led
      to a better understanding of patient needs and decreased the number of failed
      procedures. The scope of magnetic resonance imaging diagnostics has expanded to
      include urology, otolaryngology, and neonatal evaluation. Although infants and
      children constitute the majority of patients, many adults also require anesthesia
      for magnetic resonance imaging and present their own challenges. SUMMARY:
      Anesthesia and sedation during magnetic resonance imaging have a unique set of
      constraints. However, most of the standards of modern, safe anesthetic care can
      be met in this environment. The growing experience at many hospitals has
      demonstrated that a wide range of patients can receive safe care during magnetic
      resonance imaging.

PMID- 17019237
TI  - Interventional radiology.
AB  - PURPOSE OF REVIEW: The capabilities of interventional radiology are developing
      faster than perhaps any other branch of medicine. Coupled with and fuelled by
      parallel advances in computer technology, medical physics and developments in
      endovascular catheter technology, interventional radiologists are innovating not
      only replacements for open surgeries, but entirely new therapies as well. This
      has, however, provided a range of new potential complications for the patient
      and, in contrast to other areas, presents risks for the anesthesiologist as well.
      RECENT FINDINGS: The techniques involved in interventional radiology have found
      applications throughout not only medicine but surgery in particular. Here there
      has been a medicalization of surgical procedures. CT scanning has evolved to the
      extent that it is now possible to utilize multislice CT scanners, ones with
      multiple, flat panel digital detectors, to provide real time CT fluoroscopy.
      Similarly this technology has facilitated the construction of hybrid iMR/X-ray
      systems, thus enabling dual modality imaging without moving the patient. Another
      facet of the new breed of iMR systems is their integration in real time with
      computerized, frameless stereotactic navigation systems. This has enabled the
      radiological image to keep pace with the changes in anatomy consequent to
      anesthetic and surgical manipulations. SUMMARY: In the light of these new
      developments in interventional radiology there is much research to be done.
      Further developments in imaging and computer processing technology will doubtless
      make possible the real time integration of anatomical image with metabolic state
      and functional anatomy. The impact of the hazards of these new techniques on the
      safety of anesthesia has, however, been the subject of virtually no research. A
      particularly needy area will be the ergonomics of the delivery of anesthesia care
      in these new environments.

PMID- 17019238
TI  - Pediatric sedation: can it be safely performed by non-anesthesiologists?
AB  - PURPOSE OF REVIEW: The purpose of the present review is to provide the reader
      with a synopsis of the recent literature on sedation of children by non
      anesthesiologists. RECENT FINDINGS: Health care centers are experiencing an
      increasing demand for sedation of pediatric patients. Whether provided by
      physician anesthesiologists, nurse anesthetists, or appropriately credentialed
      non-anesthesia clinicians, this increase is a reflection of new advances in the
      area of diagnostic imaging, better pharmacologic agents, and a heightened
      awareness of the psychologic needs of children. By definition anesthesiologists
      are the experts when it comes to providing sedation to patients. For pediatric
      patients, pediatric anesthesiologists provide the most appropriate
      specialization. However, because of insufficient manpower, anesthesiologists
      cannot adequately meet the increasing workload of providing sedation for each
      child in need. SUMMARY: In some circumstances the incidence of adverse events
      when sedation is provided by non-anesthesiologist can be high. Predicators of
      adverse outcome have been identified. Given strict adherence to sedation
      guidelines and appropriate credentialing of the sedation provider, non
      anesthesiologists can safely provide sedation for children.

PMID- 17019239
TI  - Airway management outside the operating room.
AB  - The choice of airway device for resuscitation depends on the skill of the user,
      the equipment available, the conscious state of the patient, the location of the
      patient and the probable cause of the cardiorespiratory arrest. Extraglottic
      airway devices are recommended by the European and American Resuscitation
      Councils for use when intubation skills are lacking. In this review, we discuss
      recent research relevant to the use of extraglottic airway devices in
      resuscitation.

PMID- 17019240
TI  - Current world literature.

PMID- 17019241
TI  - Awakening management after neurosurgery for intracranial tumours.
AB  - PURPOSE OF REVIEW: Major complications after intracranial surgery occur in 13-27%
      of patients. These complications may have multiple causes, but a body of
      arguments suggests that the haemodynamic and metabolic changes of anaesthesia
      recovery may be responsible for intracranial complications. The aim of this
      review is to explain the rationale of this hypothesis and analyse the recent
      studies relevant to neuroanaesthesia recovery. RECENT FINDINGS: Rapid recovery
      and extubation after intracranial tumour surgery is desirable in order to make an
      early diagnosis of intracranial complications. Since light pharmacological
      sedation may worsen a neurological deficit, short-acting anaesthetics are
      preferable intraoperatively. Extubation in the operating room, however, may be
      associated with agitation, increased oxygen consumption, catecholamine secretion,
      hypercapnia and systemic hypertension. This may exacerbate cerebral hyperaemia
      observed even during an uneventful recovery, leading to cerebral oedema or
      haemorrhage. SUMMARY: Pain, hypothermia, hypercapnia, hypoxia, hypoosmolality,
      hypertension, and anaemia should be avoided during emergence. Early emergence is
      associated with minimal haemodynamic and metabolic changes. If there is any doubt
      as to whether the patient should be extubated in the operating room, a gradual
      emergence in the intensive care unit makes it possible to decide whether or not
      extubation can be performed safely.

PMID- 17019242
TI  - Assessment of cerebral pressure autoregulation.
AB  - Cerebral pressure autoregulation, a sensitive homeostatic mechanism important for
      the control of cerebral blood flow, is impaired by disease pathology and some
      drugs commonly used during anaesthesia. Therefore, the assessment of cerebral
      pressure autoregulation can help optimize cerebral blood flow in patients who
      have suffered neurological insults. In this article, we outline the means
      available for testing cerebral pressure autoregulation, thus allowing the reader
      to decide on the best strategy to adopt in their particular operating theatre and
      intensive care setting.

PMID- 17019243
TI  - Multimodality monitoring in severe head injury.
AB  - PURPOSE OF REVIEW: This review describes recent advances in multimodal
      neuromonitoring of patients following severe head injury during the period from
      2001 to 2002. RECENT FINDINGS: Monitoring intracranial pressure is considered a
      standard part of therapy despite a lack of randomized studies comparing patients
      with and without intracranial pressure monitoring. Jugular oximetry and brain
      tissue oxygen pressure monitoring are being used more frequently as part of a
      treatment protocol. Intracerebral microdialysis, despite the widespread use as a
      research tool, still cannot be considered a standard in clinical monitoring.
      These new monitoring devices may provide useful insight into the evolution of
      brain injury. SUMMARY: Technology is rapidly changing the nature of
      neuromonitoring. New devices are becoming available which make the monitoring
      truly multimodal. Studies are needed to determine how to best incorporate these
      new parameters into effective management protocols.

PMID- 17019244
TI  - Advances in understanding protection from cerebral ischemia.
AB  - PURPOSE OF REVIEW: Cerebral ischemia and protection is a large field, so for the
      purposes of this review, which focuses on results published in the last 9 months,
      we have chosen to discuss a few aspects of ischemia in which our understanding
      has advanced significantly in this period of time. Recent progress in the
      clinical use of hypothermia for neurological protection as well as laboratory
      progress on the role of stress proteins, estrogen and a few other potential
      adjuncts will be discussed. RECENT FINDINGS: Two papers have now been published
      documenting improved neurological outcome in patients treated with hypothermia
      following cardiac arrest, both using randomized clinical trial designs. These
      reports and several laboratory studies identifying mechanisms of hypothermic
      brain protection are reviewed. In understanding the mechanisms underlying
      protection by estrogens, new results on both direct vascular effects and a
      demonstration that estrogens can reduce apoptosis are presented. The third area
      to be described is current progress in identifying mechanisms of stress protein
      protection from ischemia, in which new mechanisms have been identified with the
      demonstration of inhibition of several points in the cell death cascade. The
      remaining areas considered touch on the effects of approaches that reduce
      inflammation by blocking adhesion molecules, those that reduce free radical
      production and those that improve blood rheology. SUMMARY: An important common
      theme in brain protection is reduction of cell death by blocking apoptosis or
      programmed cell death. While the use of hypothermia should now enter clinical
      practice, many areas of brain injury require further studies both to define
      injury mechanisms and to translate these understandings into clinically useful
      treatments to reduce ischemic brain injury.

PMID- 17019245
TI  - The benefits of regional anaesthetic techniques appear to increase but the risks
      do not disappear.

PMID- 17019246
TI  - Ophthalmic regional anaesthesia.
AB  - PURPOSE OF REVIEW: To summarize recent knowledge concerning ophthalmic regional
      anaesthesia. RECENT FINDINGS: Ophthalmic regional anaesthesia has changed
      considerably over the past few years. Alternatives to retrobulbar anaesthesia
      have been proposed to reduce the number of complications without detriment to
      efficiency. Finally new local anaesthetics have been adopted and the indications
      have broadened, especially in vitroretineal surgery. SUMMARY: New developments in
      ophthalmic regional anaesthesia are presented in this review. Different methods,
      indications and side effects are described in order to facilitate the clinician's
      choice, without any claim to single out an ideal technique.

PMID- 17019247
TI  - Clonidine--a potent analgesic adjuvant.
AB  - PURPOSE OF REVIEW: The alpha(2)-adrenoceptor agonist clonidine is one of the most
      widely investigated substances in anaesthesia and pain therapy. Recently,
      numerous experimental and clinical studies have allowed a better understanding of
      its underlying mechanisms of action and interactions with other analgesic drugs.
      RECENT FINDINGS: Several experimental studies have shown that clonidine may
      improve the analgesic effect of anti-inflammatory agents and also have
      significant peripheral antinociceptive effects. Volunteer and clinical studies
      have demonstrated analgesic effects of clonidine after systemic administration,
      whereas local administration of plain clonidine (e.g. intra-articular,
      intravenous regional) showed only limited clinical efficacy. The major clinical
      place of clonidine may thus be as an adjuvant to other analgesics, as shown in a
      number of studies in which clonidine has been investigated in combination with
      local anaesthetics, opioids and ketamine. An increasing number of studies have
      now investigated clonidine in paediatric patients and have demonstrated that the
      effects are generally similar to those in adults. Furthermore, it seems that in
      paediatric patients the side-effects of clonidine are predictable and of limited
      clinical importance. SUMMARY: During the past decade clonidine has been
      investigated as an adjuvant for general and regional anaesthesia and in the
      postoperative period. There is no doubt that clonidine improves analgesia after
      systemic, spinal or peripheral opioids, and prolongs the analgesic action of most
      local anaesthetics. The side-effects of usual doses of clonidine are predictable.
      Given the clinical experience of an increasing number of hospitals, clonidine
      should no longer be considered an experimental drug, but a useful addendum to the
      pharmacological armamentarium.

PMID- 17019248
TI  - Epidural block: technical aspects and complications.
AB  - In continuous epidural anaesthesia we rely heavily on the 'test dose' to confirm
      correct placement of the catheter. This is not always accurate and there are a
      number of new techniques designed to provide better information about epidural
      needle and catheter placement. These include: electrical stimulation of the
      catheter, use of ultrasound and the application of simple geometry. The use of
      epidurals in patients undergoing coronary artery bypass graft surgery is
      controversial because of the risk of vertebral canal haematoma. Neurological
      complications may arise during administration of the block, since the needle or
      catheter may result in direct nerve trauma. The injection of irritant drugs can
      also cause neurological damage. We must therefore be meticulous when injecting
      drugs into the epidural space. The increasing use of anticoagulant therapy in
      surgical patients and, in particular, the variety of low molecular weight
      heparins available, may make it difficult to safely perform epidural anaesthesia.

PMID- 17019249
TI  - Obstetric epidural analgesia.
AB  - PURPOSE OF THE REVIEW: There has recently been a growing interest in developing
      and modulating the techniques of neuraxial analgesia to meet the changing
      individual needs of parturients for pain relief during the course of labour and
      delivery. RECENT FINDINGS: Neuraxial analgesia is now very safe. Modern low-dose
      spinal-epidural regimens provide efficacious analgesia, stable maternal
      haemodynamics and few tolerable side effects. Complications are possible,
      however, due to the invasive nature of the technique, patient characteristics or
      medical malpractice. SUMMARY: Labour epidural analgesia still remains the 'gold
      standard' of obstetric pain management, although spinal analgesia with the single
      injection technique is an attractive option due to its simplicity, reliability
      and efficacy. Up till now, there has been no single new drug to overcome the
      superiority of neuraxial analgesia in obstetrics.

PMID- 17019250
TI  - Paediatric caudal and epidural analgesia.
AB  - PURPOSE OF REVIEW: Epidural blocks (caudal, lumbar or thoracic) are of common use
      in paediatric patients for special procedures such as open fundoplication as well
      as for postoperative analgesia. However, because neonates and infants have lower
      metabolic capacities and specific anatomy as compared to adults, the dose of
      local anaesthetics and the way of their administration need careful attention.
      RECENT FINDINGS: Recent pharmacokinetic studies have more precisely identified
      the differences in pharmacokinetics between age groups, and between local
      anaesthetic agents. In that respect, ropivacaine exhibits a unique
      pharmacokinetic profile. Among all adjuvant drugs proposed so far, S-ketamine is
      promising; however, complete safety in case of injection into the cerebrospinal
      fluid must be checked before routine use. Thoracic epidural anaesthesia is
      technically difficult, and carries a potential risk of spinal cord puncture.
      Numerous techniques have been proposed to avoid this risk. The advancement of a
      catheter into the epidural space after caudal insertion has long been proposed by
      German and Italian authors, but for anatomical reasons, this technique is only
      possible in young infants. Some improvement of the original technique using
      lumbar insertion at the L4-L5 interspace has recently been suggested; the
      possibility of catheter guidance by means of electric stimulation has also been
      proposed. SUMMARY: Pharmacokinetic studies allowing safer dosing, especially with
      ropivacaine have recently been published. New techniques of thoracic epidural
      with puncture at the lumbar level are also proposed. However, all these new
      techniques need to pass the test of time.

PMID- 17019251
TI  - Brachial plexus block.
AB  - PURPOSE OF REVIEW: In recent years there has been a renewed interest in regional
      anesthesia, particularly peripheral nerve blockade, in order not only to improve
      the patient's well being, but also to meet the requirements of modern orthopedic
      surgery. These requirements include appropriate conditions to perform early and
      efficient rehabilitation. RECENT FINDINGS: The upper extremity is well designed
      for the practice of the perineural catheter technique, since we have three main
      approaches, interscalene, infraclavicular and axillary, which allow all
      territories involved in specific surgical procedures to be blocked with only one
      shot or catheter. Recent developments have focused on modification of traditional
      technical approaches, improving the safety of the procedure, finding a more
      efficient way to administer the local anesthetic through the perineural catheter,
      and examining new indications and modes of performing regional anesthesia.
      SUMMARY: Early rehabilitation is currently a key point for the success of
      orthopedic surgery. The rapid development of peripheral nerve blockade gives the
      anesthesiologist the means to face this new challenge.

PMID- 17019252
TI  - Intrathecal anesthesia.
AB  - PURPOSE OF REVIEW: Development of new drugs and special techniques, as well as
      changes in health care organization have markedly influenced the use of spinal
      block and its indications. The present review overviews recent developments in
      local anesthetic drugs, side effects and special techniques for intrathecal
      anesthesia. RECENT FINDINGS: Severe complications after spinal anesthesia are
      acceptably rare. The cardiovascular effects associated with sympathetic block are
      more frequent but may successfully be treated with volume expansion and
      administration of vasoactive drugs while the multimodal approach to prevention of
      such side effects can also reduce the incidence. Based on recent magnetic
      resonance imaging studies the volume of cerebrospinal fluid at the lumbosacral
      level is the main determinant of the effects produced by intrathecal injection of
      local anesthetic solutions. Unfortunately, it is not possible to estimate the
      volume of cerebrospinal fluid at the lumbosacral region in clinical practice, but
      it is clear that the total dose of local anesthetic injected into the
      subarachnoid space is the primary determinant of both therapeutic and unwanted
      effects of spinal anesthesia. There is overwhelming evidence of the potential
      risk for neurological dysfunction associated with spinal lidocaine. This evidence
      is even more relevant in outpatients, in whom lidocaine is primarily indicated.
      On the other hand, several studies have demonstrated the efficacy and safety of
      using small doses of long-acting agents, such as bupivacaine or ropivacaine, to
      produce a short spinal block. The addition of small doses of opioids further
      helps to minimize the dose of local anesthetic solution required, without
      affecting the recovery profile from spinal block. The extensive use of pencil
      point designs for spinal needles, and the availability of needles of very small
      size have allowed a significant reduction in the incidence of postdural puncture
      headache. SUMMARY: The changes in health care organization observed during the
      past few years have forced us to change the indications for and clinical uses of
      intrathecal anesthesia techniques in accordance with the changing needs of
      surgery. The development of new drugs and special techniques for spinal
      anesthesia will further improve the clinical use of this old but trusted
      technique.

PMID- 17019254
TI  - Cancer pain: an update of pharmacological approaches in pain therapy.
AB  - PURPOSE OF REVIEW: This review discusses clinically oriented data on advances in
      pharmacological research of cancer pain therapy carried out during the last year.
      The aim is to ascertain whether well known guidelines for cancer pain prove to be
      adequate or require modification. RECENT FINDINGS: There are alternatives to
      morphine, which is the standard drug, including oxycodone or methadone, with the
      problem of equivalence doses in the case of opioid rotation. Depending on the
      underlying pathophysiological mechanisms, adjuvant drugs are recommended, such as
      antidepressants and anticonvulsants for neuropathic pain, or bisphosphonates for
      metastasis bone pain. Current and future research will offer receptor-specific
      acting new drugs or old drugs under new indications. SUMMARY: The recommendations
      of the World Health Organization ladder remain the mainstay of cancer pain
      management. These recommendations, however, are based more on expert opinions
      than on evidence-based data.

PMID- 17019255
TI  - Management of pain after burn injury.
AB  - PURPOSE OF REVIEW: Burn pain is often under treated. Burn patients suffer from
      daily background pain as well as procedural pain. Direct mechanical and chemical
      stimulation to peripheral nociceptors, peripheral- and central sensitization
      contribute to the pathophysiology of pain. The purpose of this review is to
      discuss the current management of burn pain and also to stimulate future studies.
      RECENT FINDINGS: Background pain is best treated with mild to moderate potent
      analgesics administered regularly to maintain a steady plasma drug concentration.
      Procedural pain should be treated vigorously with intravenous opioids, local or
      even general anesthesia if needed. Opioids are the mainstay of treatment for
      severe acute pain. PCA should be used wherever applicable. Further opioids should
      not be substituted by high dose NSAIDs in the management of procedural pain.
      Hypnosis, therapeutic touch, massage therapy, distracting techniques and other
      behavioral cognitive techniques have demonstrated some intriguing impact on acute
      as well as chronic burn pain treatment. SUMMARY: There is no clear evidence to
      show that the use of opioids in acute pain may increase the likelihood of
      developing opioid dependency. Thus, pain after burn injury should be aggressively
      treated using pharmacologic and non-pharmacologic approaches. Further controlled
      studies are yet to be conducted to define appropriate treatments for different
      burn patients and to establish standard treatment protocols for burn pain.

PMID- 17019256
TI  - Chest pain: an update.
AB  - PURPOSE OF REVIEW: Chest pain is one of the most common symptoms for seeking
      acute medical care. Evidence of myocardial ischemia, however, can only be
      established in a minority of patients. The establishment or ruling out of
      myocardial ischemia is difficult and the cost is high. An effective rationale for
      ischemia detection, without unnecessary hospital admission, is needed. The
      development of chest pain units potentially offers a rapid, effective way of
      identifying patients at high risk for acute coronary syndromes, as well as those
      with a low probability of ischemia. Other cardiac or noncardiac causes of chest
      pain should also be considered. RECENT FINDINGS: Recent developments in chest
      pain, including the ruling in or out of ischemic pain by triage and different
      ischemia detection methods, are discussed. Other causes of chest pain such as
      esophageal, drug related, psychiatric and post-coronary bypass surgery pain are
      also discussed. Recent findings on syndrome X are reviewed and patients with
      myocardial infarction presenting without chest pain are discussed. SUMMARY: The
      possibility of safely and quickly ruling out myocardial ischemia by point-of-care
      biochemical analyses is reviewed, which might influence our clinical handling of
      chest pain patients. The importance of biopsychosocial factors, pain perception,
      esophageal dysfunction, drugs and the coronary artery bypass procedure in itself,
      is discussed and vital clinical information is provided for the handling of our
      chest pain patients.

PMID- 17019257
TI  - Central pain.
AB  - PURPOSE OF REVIEW: As a result of its accompanying co-morbidity, our lack of
      understanding regarding its mechanisms, and its resistance to conventional
      treatment, central pain is one of the most formidable challenges pain physicians
      are faced with. The objective of this review is to summarize recent advances in
      our understanding of the etiology, clinical presentation, and treatment of
      central pain, with special emphasis being placed on studies published within the
      past year. RECENT FINDINGS: Recent evidence suggests that not only injuries
      commonly associated with central pain, such as strokes and spinal cord lesions,
      but also disorders such as fibromyalgia, phantom limb pain and tension-type
      headaches may involve central phenomena. Perhaps because of the lack of clinical
      trials, treatment is still largely based on traditional prescribing methods and
      anecdotal evidence. Recent studies have indicated possible roles for tricyclic
      antidepressants, anti-seizure medications, and motor cortex stimulation in the
      treatment of central pain. SUMMARY: Injury to the spinothalamocortical pathways
      is a necessary, but not sufficient factor in the pathogenesis of central pain.
      Perhaps because of the similarities in mechanisms, there is considerable overlap
      between effective treatments for central pain and those for peripheral
      neuropathic pain. Our poor understanding of the etiology of central pain and the
      relative lack of effective treatments emphasize the need for further research
      into this elusive disorder.

PMID- 17019258
TI  - Current world literature.

PMID- 17019259
TI  - What's new in our understanding of obstructive sleep apnea?

PMID- 17019260
TI  - Pain management for pediatric ambulatory anesthesia.
AB  - PURPOSE OF REVIEW: New developments in analgesic drugs and techniques are being
      applied to the pediatric population. Appropriate pain management for ambulatory
      surgery patients helps to facilitate early discharge and minimize postoperative
      morbidity. RECENT FINDINGS: A variety of opioid-related drugs, as well as novel
      delivery routes for opioids, have been reported in the pediatric population. New
      pharmacokinetic information for acetaminophen has resulted in revised dosage
      recommendations; applications of the nonsteroidal antiinflammatory agents are
      also discussed. Furthermore, regional anesthesia and adjuncts are useful in the
      pediatric ambulatory surgery patient. SUMMARY: Recent data on techniques for pain
      management after pediatric ambulatory surgery will help the anesthetist develop a
      comprehensive plan for the postoperative period.

PMID- 17019261
TI  - What's new in ophthalmic anaesthesia?
AB  - PURPOSE OF REVIEW: There have been many changes in ophthalmic anaesthesia in the
      past few years. This review charts recent trends in practice. RECENT FINDINGS:
      Topical anaesthesia is gaining widespread use for ophthalmic surgery, but readers
      need to be aware that definitions vary widely; some 'topical' techniques also
      include intracameral injections and adjunctive sedation. There is now evidence on
      the relative effectiveness of different types of local anaesthesia from large
      systematic reviews. Furthermore, the notion is emerging that the traditional
      distinction between peribulbar and retrobulbar blocks may not be as clear-cut as
      previously thought. A new area of investigation is the effect of local blocks on
      pulsatile ocular blood flow. However, the risk of ocular ischaemia has yet to be
      quantified. Local anaesthesia has also been tried for posterior segment surgery
      with apparently successful results. The management of patients taking
      anticoagulants and anti-platelet agents has been examined, and it appears that
      there are risks not only in continuing therapy but also in stopping it peri
      operatively. The decision thus has to be taken on the balance of risks. SUMMARY:
      There have been significant further gains in our understanding of local
      anaesthetic eye blocks and the management of patients undergoing such procedures.

PMID- 17019262
TI  - The elderly outpatient: current anesthetic implications.
AB  - PURPOSE OF REVIEW: The present overview describes recent contributions to the
      literature with regard to choice of anesthetic techniques, approaches to
      anesthetic management of elderly outpatients undergoing arthroscopy and other
      procedures, reconsideration of the problem of postoperative delirium in the
      elderly patient, and a general summary of perioperative management and assessment
      of anesthetic risk in older adults. RECENT FINDINGS: Major advances in monitoring
      technology, pharmacology, and comprehensive preoperative assessment have reduced
      the probability of major adverse outcomes for geriatric surgical patients to low
      levels. Therefore, it has become difficult to demonstrate clear-cut superiority
      for any specific anesthetic agent or approach. Nevertheless, the need for prompt
      and complete recovery of consciousness and rapid discharge after surgery presents
      additional challenges for the anesthesiologist who is caring for elderly
      outpatients with regard to prompt recovery of cognitive function and suppression
      of nausea and vomiting. SUMMARY: The efficiency and speed with which outpatient
      surgery and anesthetic recovery can be conducted in older adults continue to
      improve. Monitors of depth of anesthesia, ultra-short-acting agents, and combined
      techniques have minimized minor complications such as nausea and vomiting, and
      have improved the speed with which these patients recover from anesthesia. A
      small proportion of elderly surgical outpatients remain at risk for residual
      postoperative cognitive dysfunction.

PMID- 17019263
TI  - Advances in airway management for outpatients.
AB  - PURPOSE OF REVIEW: As outpatient anaesthesia increases in volume so does
      research, especially in ways to reduce morbidity from relatively minor
      complications such as sore throat and hoarseness, as well as aiming to reduce
      costs and length of hospital stay. The past year has produced many studies in
      which newer airway devices have been compared with the laryngeal mask airway and
      this review evaluates them all. RECENT FINDINGS: The relatively recent
      introduction of the ProSeal laryngeal mask airway shows promise when insertion of
      a gastric tube is preferred in patients breathing spontaneously, whilst the
      intubating laryngeal mask airway has demonstrated its usefulness in those
      situations where the patient prefers to be anaesthetized but intubation may be
      difficult following classic laryngoscopy. The cuffed oropharyngeal airway and
      combitube probably only have a place in emergency airway management rather than
      elective anaesthesia. SUMMARY: Despite the introduction of new airway devices,
      some of which have specific indications for use, the classic laryngeal mask
      airway remains the 'gold standard' with which newer devices are compared. Whilst
      some of these new devices show promise in the outpatient setting, further
      research is required before their universal acceptance.

PMID- 17019264
TI  - What is the role of neuromuscular blocking drugs in ambulatory anesthesia?
AB  - PURPOSE OF REVIEW: During ambulatory anesthesia, muscle relaxants should be used
      judiciously because of their impact on operating room efficiency and the
      potential for morbidity and mortality. RECENT FINDINGS: Short-acting and low
      doses of medium-acting muscle relaxants are appropriate for the typically short
      period of anesthesia required in ambulatory settings, but they are not
      necessarily indicated. Their adverse effects range from annoying to lethal. Even
      when the effects are relatively benign, delays may reduce efficiency. Direct
      laryngoscopy and endotracheal intubation can often safely be accomplished with
      opioids and propofol, or with topical anesthesia. Procedures such as laparoscopic
      cholecystectomies can safely be performed with anesthesia via a laryngeal mask
      airway; with other procedures, a regional technique or monitored anesthesia care
      is satisfactory. New agents may improve upon currently available muscle relaxants
      in terms of rapid onset, short duration, and minimal adverse effects. SUMMARY:
      Anesthetic and surgical needs should dictate the use of muscle relaxants, and
      alternatives to their use should be considered.

PMID- 17019265
TI  - Advances in regional anesthesia for outpatients.
AB  - PURPOSE OF REVIEW: This review will bring to the reader's attention recent
      developments in the literature regarding regional anesthesia in the outpatient
      setting, and allow the reader to evaluate whether these developments are
      appropriate for inclusion in clinical practice. RECENT FINDINGS: The most
      stimulating developments in the area of regional anesthesia for outpatients
      revolve around the use of continuous analgesic therapy for outpatients after
      discharge. This is reflected in recent publications describing the use of
      continuous catheters for peripheral nerve blockade using portable pumps to
      provide 48-72 h of postoperative analgesia. These devices have raised the hope of
      opioid-free pain relief for virtually the entire duration of postsurgical pain in
      the outpatient setting. There are also increasing numbers of suggestions on ways
      to improve the quality of spinal anesthesia in the outpatient setting,
      particularly by using lower doses of lidocaine to reduce the problem of transient
      neurologic symptoms after spinal blockade. Several authors have investigated the
      cost implications of regional techniques in the outpatient setting, and have
      concluded that they are very competitive with the general anesthetic techniques
      that are frequently employed. SUMMARY: Recent publications suggest additional
      ways to add regional anesthesia techniques to outpatient surgical practice,
      particularly with the promise of extensive postoperative pain relief for the
      ambulatory surgery patient.

PMID- 17019266
TI  - Ambulatory surgery: an overview.
AB  - PURPOSE OF REVIEW: Ambulatory surgery is now one of the major areas of surgical
      and anesthetic practice, with up to 70% of procedures performed in the ambulatory
      setting. This review focuses on some of the recent studies performed in day case
      anesthesia. RECENT FINDINGS: Emphasizing the economic benefits of ambulatory
      surgery, investigators have studied the cost implications of various anesthetic
      techniques and their impact on patient recovery, discharge times and readmission
      rates. Quality anesthetic management measures such as mortality, morbidity,
      postoperative stay and patient satisfaction ensure that perioperative care and
      treatment are optimized. SUMMARY: Careful patient selection can minimize
      perioperative events. The concept of multimodal analgesic and antiemetic therapy,
      in combination with newer anesthetic drugs, help expand the field of ambulatory
      surgery.

PMID- 17019267
TI  - Innovation in medical education: the Accreditation Council for Graduate Medical
      Education Outcome Project.

PMID- 17019268
TI  - Evidence-based medicine in anesthesiology.
AB  - PURPOSE OF REVIEW: The principles of evidence-based medicine are now being
      applied in anesthesiology and intensive care medicine. The purpose of this review
      is to acquaint practitioners with the fundamentals of evidence-based medicine and
      to provide examples of how these principles can be incorporated into clinicians'
      practice. RECENT FINDINGS: Outcomes research utilizing evidence-based approaches
      are manifest in several areas of anesthesiology and intensive care medicine.
      Several examples are cited from various sub-specialty areas, including pediatric,
      obstetric, and general anesthesia, as well as intensive care medicine. SUMMARY:
      Evidence-based medicine is the term used to describe a practice paradigm that
      emphasizes the use of the best evidence available in the medical literature in
      making treatment decisions about the care of patients. Evidence-based approaches
      to care integrate individual expertise with data from externally conducted
      systematic research. Although evidence-based medicine has its origins in the
      'treating' and 'diagnosing' specialty of internal medicine, its tenets are
      applicable to 'non-therapeutic' specialties such as anesthesiology and intensive
      care medicine. This review illustrates how evidence-based principles can be
      incorporated into the practice of perioperative medicine.

PMID- 17019269
TI  - Training requirements for peripheral nerve blocks.
AB  - PURPOSE OF REVIEW: To review the current recommendations and literature on
      training in regional anesthesia and suggest an improved model to prepare
      graduating residents better in the practice of regional anesthesia. RECENT
      FINDINGS: Patient satisfaction, a growing demand for cost-effective anesthesia,
      and a favorable postoperative recovery profile have all resulted in the growing
      demand for regional anesthesia. However, it has been well established that the
      current teaching of regional anesthesia is suboptimal. SUMMARY: A structured
      regional anesthesia rotation, a dedicated team of mentors with training in
      regional anesthesia, and adequate clinical volume are a pre-requisite for
      adequate training, but they may not be available in many anesthesia residency
      training programs. As the demand for regional anesthesia continues to increase in
      the years to come, it is imperative to ensure adequate education of graduating
      residents to meet this demand. In order to achieve this goal, the present
      recommendations should be re-evaluated, and perhaps a proficiency in a core group
      of widely applicable and relatively simple nerve blocks should be mastered by all
      graduates.

PMID- 17019270
TI  - Noninvasive cardiac output monitoring.
AB  - PURPOSE OF REVIEW: In an effort to provide high-quality intensive care without
      increasing morbidity and possibly decreasing mortality, noninvasive means of
      monitoring hemodynamics have been developed. Recently, commercially available
      monitoring techniques have been afforded the intensivist for just this purpose.
      This review will discuss the various means available, their limitations and
      recent literature describing their clinical use in comparison with pulmonary
      artery catheterization. RECENT FINDINGS: Each method has been tested clinically,
      some more so than others. The general consensus is that each method correlates
      well with pulmonary artery catheterization. Each method, however, has
      limitations. Users must be familiar with the limitations and aware of which
      method is most appropriate for their patients. In general, the derived data
      provided by the noninvasive methods parallel those of pulmonary artery
      catheterization, with the exclusion of some commonly used variables (i.e. mixed
      venous oxygen, wedge pressure). Some novel variables derived from the new
      techniques can provide analogous information to that gathered from the pulmonary
      artery catheter. SUMMARY: In summary, the methods commercially available today to
      measure hemodynamics in a noninvasive fashion offer good correlation to the
      traditional data derived from pulmonary artery catheterization. Pulmonary artery
      catheterization is considered, by most, to be the standard by which to compare
      other methods and will most likely remain so. This is due to a long history of
      reliance and clinical familiarity with its use. Additional clinical studies will
      need to be performed in a heterogeneous population of patients (trauma, burn,
      sepsis etc.) to enable better determination of reliability and limitations in
      various clinical scenarios. Overcoming the clinician's personal preference to
      rely on traditional pressure-derived data will also be a large obstacle to
      overcome.

PMID- 17019271
TI  - Pacemakers, recent directions and developments.
AB  - PURPOSE OF REVIEW: Pacemaker and implantable cardiovertor defibrillator
      utilization is evolving rapidly. Expanding indications are reviewed. RECENT
      FINDINGS: Current pacemakers are smaller, more dependable, longer lasting and
      have rate-adaptive features. Implantable cardiovertor defibrillators use
      transvenous leads and have advanced pacing abilities. Primary pacing indications
      remain sinus node dysfunction or atrioventricular conduction abnormalities. Dual
      chamber pacemakers compared with single chamber ventricular pacemakers, have
      small quality of life advantages and result in less atrial fibrillation, but
      decrease stroke rates and mortality. In congestive heart failure patients with
      delayed ventricular conduction, cardiac resynchronization therapy (atrially timed
      biventricular pre-excitation) improves physiological parameters, performance
      indices and quality of life. Atrial arrhythmias may be prevented or treated with
      appropriate pacing strategies. Pacing-related improvements for symptomatic
      neurally mediated syncope and symptomatic hypertrophic obstructive cardiomyopathy
      have been demonstrated. For patients with coronary artery disease and low
      ejection fractions, implantable cardiovertor defibrillators are well established
      in the secondary prevention of sudden death, and may be helpful for primary
      prevention if there are inducible ventricular arrhythmias. Combining cardiac
      resynchronization and implantable cardiovertor defibrillators in similar patients
      is under investigation. The role of atrial defibrillators is being defined.
      Electromagnetic interference remains possible with these devices, particularly in
      electromagnetically hostile environments. SUMMARY: More pacemakers and
      implantable cardiovertor defibrillators will be encountered. Despite increasing
      sophistication, most often only basic anti-bradycardia modes are essential in the
      perioperative setting. Understanding the indications for implantation will help
      the anesthesiologist better support the physiological needs of the patient.
      Existing perioperative pacemaker-related guidelines for the anesthesiologist
      still apply.

PMID- 17019273
TI  - Current world literature.

PMID- 17019272
TI  - Therapeutic drug monitoring.
AB  - PURPOSE OF REVIEW: Traditionally, therapeutic drug monitoring has been used for
      the management of epilepsy, cardiac arrhythmias, asthma and depression. This
      review provides an update, particularly for the newer clinical applications, and
      how therapeutic drug monitoring (including use of analytical and interpretation
      tools) can improve clinical outcomes. RECENT FINDINGS: Improved drug assay
      methodologies and a greater understanding of pharmacokinetic and pharmacodynamic
      mechanisms has allowed the use of therapeutic drug monitoring for
      immunosuppressant drugs in organ transplant recipients, antiretroviral agents for
      HIV/AIDS and antimetabolite drugs for leukaemia. In addition, new computer
      software to analyse drug concentrations in complex populations is being developed
      and introduced into routine clinical applications to allow increasingly patient
      specific assay interpretation. SUMMARY: Therapeutic drug monitoring assists in
      improving clinical success rates and minimizing toxicity. The use of therapeutic
      drug monitoring is therefore likely to become more widespread as new modalities
      are adopted.

PMID- 17019275
TI  - Moving forward: creating a new nursing services orientation program.
AB  - Discovering ways to engage new employees and make the orientation period prior to
      unit orientation more meaningful is a challenge for staff development educators.
      This important period focuses on patient safety and employee introduction to the
      organization. This article describes the redesign of a nursing services
      orientation program that led to increased employee satisfaction and an increased
      level of comfort with preparedness to deliver safe patient care.

PMID- 17019276
TI  - Graduate nurses' comfort and knowledge level regarding tracheostomy care.
AB  - This study examined 104 new graduate nurses' (GNs) comfort level before and after
      a tracheostomy inservice educational session. Results indicate no correlation
      between reported comfort level and knowledge in caring for patients with
      tracheostomies. Findings demonstrate that GNs can benefit significantly from
      inservice education and skills integration. This suggests that hands-on skills
      content should be a priority for inclusion into nurse residency programs,
      particularly with specialized, high-risk, low-incidence nursing skills,
      regardless of how comfortable nurses report they are with a given patient
      population.

PMID- 17019278
TI  - Human immunodeficiency virus/acquired immune deficiency syndrome: a survey of the
      knowledge, attitudes, and beliefs of Texas registered nurses in the 21st century.
AB  - There exist few studies in the United States that examine the knowledge,
      attitudes, and beliefs of registered nurses regarding persons with human
      immunodeficiency virus and acquired immune deficiency syndrome. This information
      is needed to determine curriculum changes and continuing education needs.

PMID- 17019280
TI  - A review of methods to assess competency.
AB  - This article describes the various methods used for assessment of competence and
      the appropriate use of each method. It identifies the role of the manager,
      expert, and educator in the development and implementation of competency
      assessment opportunities. This article identifies a template for creating and
      assessing competence. Included in the article are examples of methods,
      competencies, and the requirements of the accreditation agency, the Joint
      Commission. The author clarifies the requirements for age-related education for
      patient caregivers and non-patient-caregivers. The role of online education and
      where the manager and the educator can find and use new methods of assessment of
      skills and knowledge for the future are discussed.

PMID- 17019281
TI  - Designing career development programs through understanding of nurses' career
      needs.
AB  - A nurse's career can be divided into the exploration, establishment, maintenance,
      and disengagement stages. Because nurses have varied career needs at different
      career stages, this article uses literature review and in-depth interviews with
      nurses to understand the features of career stages. The authors detail nurses'
      career needs in different stages and infer appropriate career development
      programs in the hospital system.

PMID- 17019282
TI  - Regional orientation program for the department of clinical neurosciences.
AB  - A regional orientation program increases the efficient and effective use of
      resources such as classroom, equipment, and educator time. It provides consistent
      information to all new nurses and maintains standards of nursing practice
      throughout the Department of Clinical Neurosciences.

PMID- 17019283
TI  - Teaching ergonomics to nursing facility managers using computer-based
      instruction.
AB  - This study offers evidence that computer-based training is an effective tool for
      teaching nursing facility managers about ergonomics and increasing their
      awareness of potential problems. Study participants (N = 45) were randomly
      assigned into a treatment or control group. The treatment group completed the
      ergonomics training and a pre- and posttest. The control group completed the pre-
      and posttests without training. Treatment group participants improved
      significantly from 67% on the pretest to 91% on the posttest, a gain of 24%.
      Differences between mean scores for the control group were not significant for
      the total score or for any of the subtests.

PMID- 17019284
TI  - Instant teaching tools.

PMID- 17019285
TI  - Preceptorship.

PMID- 17019289
TI  - The female athlete triad: do female athletes need to take special care to avoid
      low energy availability?

PMID- 17019290
TI  - Unstable shoe construction and reduction of pain in osteoarthritis patients.
AB  - PURPOSE: The purposes of this study were to assess a) the effectiveness of Masai
      Barefoot Technology (MBT) shoe in reducing knee pain in persons with knee
      osteoarthritis (OA) and (b) changes in balance, ankle and knee ROM, and ankle
      strength compared with a high-end walking shoe for 12 wk. METHODS: The research
      design was a randomized controlled trial (123 subjects, knee OA). Subjects were
      randomized to a MBT (N = 57) or a control shoe (N = 66). A Western Ontario and
      McMaster Universities (WOMAC) OA index, BMI, balance, active ROM, and ankle
      torque were quantified at week 0, 3, 6, 9, and 12. Two-sample t-tests were done
      for between-group comparisons. RESULTS: There was no significant difference
      between groups in total pain score. A significant reduction over the 12-wk period
      was found for both shoe conditions (-42/500 or 25.6% MBT, -46.2 or 27.1%
      control). There was no significant group difference in pain during walking (t = 
      1.09, P = 0.28). Pain during walking was significantly reduced by 5.2/100 mm in
      the MBT and 9.7/100 mm in the control group. Total pain showed a significant
      reduction for the MBT -27.4/500 (-16.6%) and the control group -28.9/500 (-17.0%)
      between baseline and week 3. Between week 3 and 6, there was a significant
      reduction for the MBT group only (-27.2/500 or -20.0%). There was a significant
      increase in the static balance between baseline and 12 wk in the MBT group only,
      although the difference between groups was not significant. DISCUSSION: The
      results indicate that special shoe interventions can reduce pain in subjects with
      moderate knee OA.

PMID- 17019291
TI  - Effect of high cardiorespiratory fitness and high body fat on insulin resistance.
AB  - PURPOSE: High cardiorespiratory fitness (CRF) dramatically lowers risk for
      cardiometabolic disease in overweight and obese individuals. This effect is
      likely attributable to the inverse relationship between high CRF and insulin
      resistance. In this study, the independent effects of high body fat and high CRF
      on insulin resistance were assessed. METHODS: The blood glucose and insulin
      responses to an oral glucose tolerance test were measured in 10 overweight women
      with high CRF (OF), 9 lean women with high CRF (LF), and 10 overweight women with
      low CRF (OU). RESULTS: Fasting plasma glucose (P = 0.77), insulin (P = 0.23), and
      triacylglycerol (P = 0.99) concentrations were similar between OF and LF, with
      mean values in both groups lower than in OU. The glucose area under the curve
      (AUC) was not different between LF and OF (P = 0.28) and was significantly higher
      in OU. Insulin sensitivity, estimated from the composite insulin-sensitivity
      index (C-ISI), was slightly but significantly lower in OF compared with LF.
      Similarly, insulin AUC was 43% lower in LF compared with OF, although this
      difference was not statistically significant (P = 0.08). Insulin AUC was 50%
      higher (P = 0.04) and C-ISI was 35% lower (P = 0.09) in OU compared with OF.
      CONCLUSION: Compared with lean fit women, estimated insulin sensitivity was only
      slightly lower and plasma triacylglycerols were almost identical in overweight
      women with equally high CRF despite a twofold elevation in body fat percentage.

PMID- 17019292
TI  - Population trends in leisure-time physical activity: Minnesota Heart Survey, 1980
      2000.
AB  - PURPOSE: Twenty-year trends in lifestyle (leisure, household, and transportation
      related) physical activity and leisure-time physical activity (LTPA) were
      evaluated in the Minnesota Heart Survey (MHS), a population-based surveillance
      study to monitor trends in cardiovascular risk factor levels among residents of
      the Minneapolis-St. Paul metropolitan area. METHODS: The Minnesota LTPA
      questionnaire was administered to adult participants in one of five cross
      sectional MHS surveys conducted in 1980 (N = 1626), 1985 (N = 2292), 1990 (N =
      2552), 1995 (N = 2432), and 2000 (N = 3089). Occupational activity was queried in
      1980, 1995, and 2000. Age-adjusted, gender-specific geometric means of lifestyle
      physical activity and LTPA and of light-, moderate-, and vigorous-intensity
      activities were calculated for each survey. The proportion of adults
      participating in regular physical activity for 30 and 60 min x d(-1) was
      reported. RESULTS: Male gender, younger age, higher educational status, and
      employment were characteristic of greater participation in physical activity.
      Daily energy expenditure from lifestyle physical activity and LTPA increased
      between 1980 and 2000 in both genders, and workplace activity decreased. Using
      direct questions, the prevalence of men and women participating in 30 or more
      minutes of physical activity at least five times per week ranged from 8 to 12%,
      with no time trend. Only 1% of participants participated 60 min daily. Overall,
      BMI was 1-2 kg x m(-2) lower among individuals who participated regularly in
      physical activity. CONCLUSIONS: Although energy expenditure was lower than
      national recommendations, greater physical activity was associated with lower
      body mass. Public health strategies are needed to facilitate participation in
      physical activity, especially for women, elderly, and less educated individuals.

PMID- 17019293
TI  - Active travel to school and cardiovascular fitness in Danish children and
      adolescents.
AB  - PURPOSE: Active travel to school provides an opportunity for daily physical
      activity. Previous studies have shown that walking and cycling to school are
      associated with higher physical activity levels. The purpose of this study was to
      investigate whether the way that children and adolescents travel to school is
      associated with level of cardiovascular fitness. METHODS: Participants were
      recruited via a proportional, two-stage cluster sample of schools (N = 25) in the
      region of Odense, Denmark as part of the European Youth Heart Study (EYHS). Nine
      hundred nineteen participants (529 children, age 9.7 +/- 0.5 yr; 390 adolescents,
      age 15.5 +/- 0.4 yr) completed a maximal cycle ergometer test to assess
      cardiorespiratory fitness (Wmax x kg(-1)). Mode of travel to school was
      investigated by questionnaire. Physical activity was measured in 531 participants
      using an accelerometer. Regression analyses with robust standard errors and
      adjustment for confounders (gender, age, body composition (skinfolds), pubertal
      status, and physical activity) and the cluster sampling procedure were used to
      compare fitness levels for different travel modes. Multinomial logistic
      regression was applied to assess the odds for belonging to quartiles of fitness.
      RESULTS: Children and adolescents who cycled to school were significantly more
      fit than those who walked or traveled by motorized transport and were nearly five
      times as likely (OR 4.8; 95% CI 2.8-8.4) to be in the top quartile of fitness.
      CONCLUSION: Cycling to school may contribute to higher cardiovascular fitness in
      young people.

PMID- 17019294
TI  - Children's pedometer-determined physical activity during the segmented school
      day.
AB  - PURPOSE: To describe the sex-specific patterns of school children's daily
      pedometer-determined physical (PA) during physical education (PE), recess and
      lunchtime, and before and after school. METHODS: Eighty-one sixth-grade students
      (28 boys, age = 11.9 +/- 0.4 yr, BMI = 18.8 +/- 4.1 kg x m(-2); 53 girls, 11.8 +/
      0.5 yr, BMI = 20.2 +/- 4.6 kg x m(-2)) wore pedometers for four school days and
      were prompted to record steps accumulated at arrival and departure from school
      and during pre- and postrecess, lunchtime, and PE class. RESULTS: Boys took
      significantly (P < 0.001) more steps per day than girls: 16,421 +/- 5,444 vs
      12,332 +/- 3,056 steps per day, and more steps during release time (e.g., before
      school Delta = 1289 steps, recess Delta = 479 steps, lunchtime Delta = 608 steps,
      and after-school Delta = 1872 steps) but the same number of steps during
      structured PE classes (1429 +/- 567 vs 1410 +/- 445 steps; P = 0.87). Lunchtime
      PA represented the most important source of daily PA (15-16%) obtained during
      school hours for both boys and girls, whereas recess accounted for 8-9% and PE
      class accounted for 8-11% of total steps per day. Regardless, almost half of
      daily steps taken are attributable to after-school activities. CONCLUSION: These
      data provide greater understanding of sex-specific PA patterns and the relative
      contribution of distinct segments of the school day to school children's total
      PA.

PMID- 17019295
TI  - Effects of unaccustomed and accustomed exercise on the immune response in
      runners.
AB  - PURPOSE: To test the hypothesis that long-term immunological response may be
      different after accustomed concentric and unaccustomed eccentric exercise in
      endurance-trained men. METHODS: Fourteen highly endurance-trained male runners
      performed two bouts of high-intensity exercise with at least 2-wk intervals
      between bouts. Concentric exercise consisted of a 60-min level run with a
      targeted heart rate of 80% VO2 peak. Eccentric exercise was conducted lying on a
      specially designed exercise rack, eliciting eccentric action of the musculus
      quadriceps femoris. Blood samples were taken before and 1, 6, 24, 72, and 144 h
      after exercise to determine creatine kinase (CK), C-reactive protein (CRP), and
      interleukin-6 (IL-6). Lymphocyte subset distribution was assessed using flow
      cytometry. RESULTS: We found a significant (P < 0.05) increase of CD4 (eccentric:
      17%; concentric: 20%), CD3+/CD4+ (16 vs 19%), CD25+ (45 vs 29%), CD25+/CD4+ (27
      vs 50%), HLA-DR+ (20 vs 15%), HLA-DR+/CD4+ (16 vs 67%), and CD19+/CD45+ (52 vs
      103%) positive lymphocytes 1 h after both exercise bouts. However, eccentric
      exercise resulted in a significantly higher and longer (6 h) increase of
      CD25+/CD4+ and HLA-DR+/CD8+ lymphocytes and a peak increase of CK at 72 h. IL-6
      and CRP increased only after concentric exercise within the first 24 h. Both
      exercises resulted in a decrease of monocyte activation (LFA-1: CD18+/CD11a+)
      after 6 h, with an increase for the eccentric exercise part after 24 h (P <
      0.05). CONCLUSION: Accustomed concentric exercise mainly induced an acute-phase
      response, with increased CRP, IL-6, and activation of CD4 lymphocyte subsets.
      Unaccustomed eccentric exercise provided a delayed increase in CK and activation
      of monocytes and CD4+ and CD8+ subsets. Therefore, the immunological reaction
      depends not only on the type of contraction but also on the adaptation to the
      exercise.

PMID- 17019296
TI  - Dose-related effects of prolonged NaHCO3 ingestion during high-intensity
      exercise.
AB  - PURPOSE: Sodium bicarbonate (NaHCO3) ingestion may prevent exercise-induced
      perturbations in acid-base balance, thus resulting in performance enhancement.
      This study aimed to determine whether different levels of NaHCO3 intake
      influences acid-base balance and performance during high-intensity exercise after
      5 d of supplementation. METHODS: Twenty-four men (22 +/- 1.7 yr) were randomly
      assigned to one of three groups (eight subjects per group): control (C, placebo),
      moderate NaHCO3 intake (MI, 0.3 g x kg(-1) x d(-1)), and high NaHCO3 intake (HI,
      0.5 g x kg(-1) x d(-1)). Arterial pH, HCO3(-), PO2, PCO2, K+, Na, base excess
      (BE), lactate, and mean power (MP) were measured before and after a Wingate test
      pre- and postsupplementation. RESULTS: HCO3(-) increased proportionately to the
      dosage level. No differences were detected in C. Supplementation increased MP (W
      x kg(-)) in MI (7.36 +/- 0.7 vs 6.73 +/- 1.0) and HI (7.72 +/- 0.9 vs 6.69 +/-
      0.6), with HI being more effective than MI. NaHCO3 ingestion resulted
      postexercise in increased lactate (mmol x L(-1)) (12.3 +/- 1.8 vs 10.3 +/- 1.9
      and 12.4 +/- 1.2 vs 10.4 +/- 1.5 in MI and HI, respectively), reduced exercise
      induced drop of pH (7.305 +/- 0.04 vs 7.198 +/- 0.02 and 7.343 +/- 0.05 vs 7.2 +/
      0.01 in MI and HI, respectively) and HCO3(-) (mmol x L(-1)) (13.1 +/- 2.4 vs
      17.5 +/- 2.8 and 13.2 +/- 2.7 vs 19.8 +/- 3.2 for HCO3 in MI and HI,
      respectively), and reduced K (3.875 +/- 0.2 vs 3.625 +/- 0.3 mmol x L(-1) in MI
      and HI, respectively). CONCLUSION: NaHCO3 administration for 5 d may prevent acid
      base balance disturbances and improve performance during anaerobic exercise in a
      dose-dependent manner.

PMID- 17019297
TI  - Aerobic influence on neuromuscular function and tolerance during passive
      hyperthermia.
AB  - PURPOSE: To determine the role of aerobic fitness on central neuromuscular
      activation and maximal voluntary contractile force during hyperthermia. METHODS:
      Thirty-seven healthy males in three distinct groups based on aerobic fitness and
      training history were passively heated using a liquid conditioning garment in a
      hot (35 degrees C, 50% RH) environment with the intention of testing
      neuromuscular function with whole-body hyperthermia. Of these initial
      participants, 11 of the 13 highly fit (HF; VO2max = 71.2 +/- 5.9 mL x kg(-1) x
      min(-1), body fat = 5.6 +/- 1.9%), 11 of the 13 moderately fit (MF; 57.2 +/- 4.2
      mL x kg(-1) x min(-1), 11 +/- 3.4%), and 4 of the 11 lower-fit (LF; 49.6 +/- 1.1
      mL x kg(-1) x min(-1), 19.4 +/- 2.6%) individuals tolerated heating to 39.0
      degrees C, with the remainder terminating the experimental protocol early.
      Maximal force output and voluntary activation were examined during a 10-s maximal
      isometric knee extension. RESULTS: Passive heating attenuated force production (
      61.7 +/- 69.6 N change from initial values) and decreased voluntary activation
      (8.6 (12.6), 18.1 (12.4), and 6.1 (3.1)% for HF, MF, and LF training groups,
      respectively). Cardiovascular strain moderately increased to 60 +/- 14% (P <
      0.001), whereas HF and MF had significantly higher MAP than LF at the end of
      heating (98 +/- 15, 99 +/- 7, and 79 +/- 5 mm Hg for HF, MF, and LF,
      respectively; P < 0.05). However, the ability to tolerate passive heating to 39.0
      degrees C (and above) differed between the HF and MF compared with LF, despite no
      difference in their psychophysical rankings of thermal sensations and/or
      (dis)comfort. CONCLUSION: Low aerobic fitness and activity level are associated
      with a decreased tolerance to passive hyperthermia. However, at high body
      temperatures, maximum force production and voluntary activation were impaired to
      an equal level regardless of training status.

PMID- 17019298
TI  - No effect of 5% hypohydration on running economy of competitive runners at 23
      degrees C.
AB  - PURPOSE: Although running economy (RE) is recognized as an integral component of
      successful endurance performance and is affected by numerous factors, little is
      known about the influence of body water loss on RE. This investigation examined
      the effects of hypohydration (HY) on RE and associated physiological responses.
      METHODS: Ten highly trained collegiate distance runners (mean +/- SD; age, 20 +/-
      3 yr; height, 178.5 +/- 6.3 cm; body mass, 66.7 +/- 5.4 kg; VO2max, 66.5 +/- 4.1
      mL x kg(-1) x min(-1)) participated in four experiments on separate days, twice
      in a euhydrated (EU) and twice in a HY state (-5.5 and -5.7% body mass loss
      achieved during 24 h). At each hydration level, subjects performed one 10-min
      treadmill run per day (23 degrees C environment), at either 70% VO2max (EU 70% or
      HY 70%) or 85% VO2max (EU 85% or HY 85%) in a randomized, repeated-measures
      design. Cardiopulmonary, metabolic, thermal, hormonal, and perceptual variables
      were measured. RESULTS: No between-treatment differences existed for RE (EU 70%,
      46.3 +/- 3.2; HY 70%, 47.2 +/- 3.8; EU 85%, 58.6 +/- 2.8; HY 85%, 58.9 +/- 4.1 mL
      x kg(-1) x min(-1)), postexercise plasma lactate concentration (EU 70%, 1.9 +/-
      0.6; HY 70%, 1.8 +/- 0.6; EU 85%, 6.5 +/- 3.5; HY 85%, 6.4 +/- 3.5 mmol x L(-1)),
      or rating of perceived exertion. HY resulted in a greater (P < 0.05 to 0.001)
      heart rate (HR), rectal temperature, and plasma norepinephrine concentration
      (NE), concurrent with reduced cardiac output, stroke volume, and respiratory
      exchange ratio. CONCLUSION: HY did not alter the RE or lactate accumulation of
      endurance athletes during 10 min of exercise at 70 and 85% VO2max. These findings
      indicate that HY had no effect on RE, but that it increased physiological strain
      in a 23 degrees C environment.

PMID- 17019299
TI  - Muscular performance after concentric and eccentric exercise in trained men.
AB  - PURPOSE: We studied previously resistance-trained men and compared the effects of
      concentric and eccentric training on performance and structural muscle
      parameters. METHODS: Seventeen trained individuals (age 26.9 +/- 3.4 yr)
      participated in 12 wk of either maximum concentric (N = 8) or eccentric (N = 9)
      resistance training of the elbow flexors. The functional performance was measured
      as the maximum concentric and eccentric strength and angular velocity at standard
      loads. Muscle cross-sectional area and cross-sectional area of single cells were
      used as measures of muscular hypertrophy. Fiber-type proportions were assessed by
      staining cells for myofibrillar ATPase. RESULTS: Both eccentric and concentric
      training increased concentric strength to a similar extent (14 vs 18%), whereas
      eccentric training led to greater increases in eccentric strength than concentric
      training did (26 vs 9%). The maximum angular velocity at all loads was enhanced
      equally in both training groups. The cross-sectional area of both the elbow
      flexors (+11%) and of the type I and type IIA fibers increased only after the
      eccentric training. In addition, the relative cross-sectional area occupied by
      the type II fibers increased from 64 to 73% after the eccentric training. There
      were only minor changes in the fiber-type proportions. CONCLUSION: The present
      data suggest that for resistance-trained men, increases in concentric strength
      and velocity performance after eccentric training are largely mediated by changes
      in fiber and muscle cross-sectional area. However, hypertrophy alone could not
      explain the increase in eccentric strength. Because the increases in strength and
      velocity performance after concentric training could not be ascribed to muscular
      adaptations alone, we suggest that they may be attributable to additional neural
      factors.

PMID- 17019300
TI  - Epstein-Barr virus serostatus: no difference despite aberrant patterns in
      athletes and control group.
AB  - PURPOSE: To investigate the Epstein-Barr virus (EBV) serostatus in an athletic
      endurance population, especially the prevalence of complex aberrant EBV antibody
      patterns. In addition, the purpose was to determine whether serology in athletes
      is more complex than in the general population. METHODS: The study protocol
      included serological testing of 202 advanced endurance athletes (biathlon,
      cycling, nordic skiing (state to international level); mean age 19 +/- 4) and 200
      control subjects (mean age 23 +/- 2). Twenty-microliter serum samples were
      examined using a strip immunoassay with antigens produced by recombinant
      techniques for detection of EBV IgG antibodies: anti-EBNA-1 (anti-EBV nuclear
      antigen-1), anti-p18, anti-p23, anti-p138, anti-p54, and anti-BZLF-1. Avidity
      determination was used to differentiate further between acute, recent, and past
      infections. RESULTS: Athletes showed 35 negative (17%), 6 unresolvable (3%), 1
      acute (0.5%), 11 recent (5%), 122 past (61%), and 27 aberrant past (mainly anti
      EBNA-1 negative) (13.5%) cases. The control group showed 31 negative (16%), 4
      unresolvable (2%), 1 acute (0.5%), 1 recent (0.5%), 135 past (68%), and 28
      (14.0%) aberrant past cases. Although endurance athletes included more recent
      infections (several months since acute infection), there was no significant
      difference (P = 0.144) in the total constellation of EBV serostatus between the
      groups. CONCLUSION: No evidence was found for the assumption that endurance
      athletes are more susceptible to EBV infections than the general population. In
      addition, no differences were found with respect to serological classical and
      aberrant complicated patterns between athletes and the control group. Those cases
      that may lead to false diagnoses of acute EBV infection in previously used test
      systems because of a negative anti-EBNA-1 are common in both groups but were
      unambiguously resolved by the Recomline EBV IgG test applied here.

PMID- 17019301
TI  - Metabolic and vascular limb differences affected by exercise, gender, age, and
      disease.
AB  - Unlike quadrupeds, human limbs are exposed to differing homeostatic challenges
      and uses. The arms are not exposed to a large hydrostatic pressure and contain a
      relatively small muscle mass that is not typically engaged in heavy work. In
      contrast, the legs have a large blood volume, experience significant hydrostatic
      pressures, and contain the majority of the body's muscle mass, which is used
      regularly to perform the significant work of locomotion. This raises the question
      of whether skeletal muscle blood flow and metabolism differ between limbs and
      whether these responses may be altered during exercise as a consequence of aging
      and disease. Initially, we examine the long standing question of how the body
      copes with the involvement of both sets of limbs and the large muscle mass that
      this entails, restrained by a finite cardiac output and a need to defend arterial
      blood pressure. We therefore evaluate the similarities and differences in
      exercising muscle blood-flow control in the upper and lower limbs, with respect
      to exercise onset kinetics, intrinsic vasoreactivity of the resistance vessels at
      rest and during exercise, and the role of gender and the aging process in limb
      specific responses. It is concluded that blood flow and pressure when multiple
      limbs are simultaneously recruited is facilitated by sympathetically mediated
      vasoconstriction. Inherent limb differences, in terms of skeletal muscle
      metabolism and blood flow, do exist, and elucidating the mechanisms underlying
      limb-specific adaptations will be important for interpreting abnormal vascular
      function attributable to healthy aging and disease.

PMID- 17019302
TI  - Are the arms and legs in competition for cardiac output?
AB  - Oxygen transport to working skeletal muscles is challenged during whole-body
      exercise. In general, arm-cranking exercise elicits a maximal oxygen uptake
      (VO2max) corresponding to approximately 70% of the value reached during leg
      exercise. However, in arm-trained subjects such as rowers, cross-country skiers,
      and swimmers, the arm VO2max approaches or surpasses the leg value. Despite this
      similarity between arm and leg VO2max, when arm exercise is added to leg
      exercise, VO2max is not markedly elevated, which suggests a central or cardiac
      limitation. In fact, when intense arm exercise is added to leg exercise, leg
      blood flow at a given work rate is approximately 10% less than during leg
      exercise alone. Similarly, when intense leg exercise is added to arm exercise,
      arm blood flow and muscle oxygenation are reduced by approximately 10%. Such
      reductions in regional blood flow are mainly attributed to peripheral
      vasoconstriction induced by the arterial baroreflex to support the prevailing
      blood pressure. This putative mechanism is also demonstrated when the ability to
      increase cardiac output is compromised; during exercise, the prevailing blood
      pressure is established primarily by an increase in cardiac output, but if the
      contribution of the cardiac output is not sufficient to maintain the preset blood
      pressure, the arterial baroreflex increases peripheral resistance by augmenting
      sympathetic activity and restricting blood flow to working skeletal muscles.

PMID- 17019303
TI  - Aging, exercise, and limb vascular heterogeneity in humans.
AB  - Unlike quadrupeds, human limbs are exposed to differing homeostatic challenges
      and uses, which results in significant functional heterogeneity between the arms
      and legs. In these ACSM symposium proceedings, we report findings from three
      studies with the overall aim of investigating between-limb vascular differences
      through evaluation of arm (brachial artery) and leg (common, superficial, and
      deep femoral arteries) limb blood flow (ultrasound Doppler) during isolated-limb
      specific exercise and after postcuff occlusion hyperemia. In a study of young,
      trained cyclists, a substantial conduit vessel vasodilation (deep femoral artery,
      approximately 9%) was observed during exercise, but responsiveness normalized to
      shear stimuli was still less than a conduit vessel in the arm. A subsequent aging
      study did not demonstrate any significant difference in resting leg or arm blood
      flow between young and old subjects when flow was normalized for muscle mass.
      However, we observed an approximately 10-15% reduction in exercising leg blood
      flow and vascular conductance in these older subjects, whereas exercising arm
      blood flow was similar between age groups. A separate aging study evaluated age
      related changes in flow-mediated vasodilation (FMD), with the older group
      enrolled in a 6-wk knee-extensor exercise training program. Before training, a
      significant FMD was observed in the arm of young (3 +/- 1%) but not old (1 +/-
      1%) subjects, and a significant leg FMD was observed in both groups. However,
      pretraining arm vasodilation was similar between young and old when normalized
      for shear rate. Exercise training significantly improved arm FMD (5 +/- 1%),
      whereas leg FMD was unchanged. Collectively, these studies demonstrate a
      significant between-limb vascular heterogeneity in humans that is influenced by
      age and by exercise training.

PMID- 17019304
TI  - Muscle blood-flow dynamics at exercise onset: do the limbs differ?
AB  - Common approaches to understanding control of muscle blood flow in exercise focus
      on the contributions of various putative vasoregulatory mechanisms to the
      magnitude of the steady-state response. The application of systems-control
      principles offers a unique approach to characterizing and quantifying the non
      steady-state adaptation of muscle blood flow with exercise onset. Information
      gained from this approach provides novel insight into the nature of control
      mechanisms governing physiological responses to exercise. This review is intended
      to provide the reader with an understanding of 1) exercise models, methodology
      for measuring muscle blood flow, and analysis approaches for quantifying muscle
      blood-flow dynamics; 2) what is currently known about the dynamic response of
      muscle blood-flow control mechanisms in humans; and 3) the similarities and
      differences in exercising muscle blood-flow control in the upper versus the lower
      limbs in humans.

PMID- 17019305
TI  - Is there a difference in vascular reactivity of the arms and legs?
AB  - The arterial vessels within the arms and legs are exposed to different
      hydrostatic pressures and blood-flow demands during the course of daily life.
      There is compelling indirect evidence that arterial reactivity differs in the
      arms and legs of humans; greater blood-flow responses to physiological
      vasodilator stimuli are generally reported in the arms of healthy younger
      subjects, whereas greater sympathetically mediated vasoconstrictor responsiveness
      is generally observed in the legs. Limb blood-flow responses to local arterial
      infusions of vasoactive agents reveal a similar pattern of heterogeneity in human
      arms versus legs. The advantages and assumptions of these pharmacological
      approaches for evaluating limb arterial reactivity are discussed, and
      methodological issues pertaining to the normalization and interpretation of
      vascular responses in the human arm and leg are critically examined. The article
      concludes with recent data from our laboratory indicating that limb-specific
      variation in arterial function may be age-, sex-, and physical activity
      dependent.

PMID- 17019306
TI  - A biomechanical analysis of the long-jump technique of elite female amputee
      athletes.
AB  - PURPOSE: The purpose of this study was to investigate whether female lower-limb
      amputees conform to the established long-jump model and to compare the kinematics
      of the approach and take-off phases for elite female transfemoral and transtibial
      amputee long jumpers. METHODS: Eight female transfemoral and nine female
      transtibial amputee athletes were videotaped (sagittal plane movements at 50 Hz)
      from third-to-last step to take-off during the 2004 Paralympic Games long-jump
      finals. After digitizing and reconstruction of 2D coordinates, key variables were
      calculated at each stride and during contact with the take-off board.
      Additionally, approach speed during the run-up of each jump was recorded (100 Hz)
      using a laser Doppler device (LDM 300 C Sport, Jenoptik Laser, Jena, Germany).
      RESULTS: The transfemoral amputees had a consistently higher center of mass
      height on the last three steps before take-off than the transtibial amputees.
      However, at touch-down onto the take-off board, they lowered their center of mass
      excessively so that from touch-down to take-off, they were actually lower than
      the transtibial amputees. This resulted in a greater negative vertical velocity
      at touch-down and may have inversely affected their jump performance. CONCLUSION:
      Female transtibial athletes conformed to the long-jump model, although
      adaptations to this technique were displayed. Female transfemoral athletes,
      however, exhibited no relationship between take-off speed and distance jumped,
      which may be attributable to their excessive lowering of their center-of-mass
      height at touch-down onto the take-off board. It is recommended that coaches and
      athletes proceed with caution when trying to replicate techniques used by able
      bodied athletes because adaptations to the constraints of a prosthesis should be
      considered.

PMID- 17019307
TI  - Effect of fatigue on tibial impact accelerations and knee kinematics in drop
      jumps.
AB  - PURPOSE: The principle of specificity suggests that it may be beneficial to
      undertake plyometric drop-jump training when fatigued. However, this may increase
      peak-impact accelerations and therefore increase the risk of injury. The aims of
      the study were to determine if whole-body fatigue (i) increased peak-impact
      acceleration on the proximal tibia during plyometric drop jumps and (ii) produced
      associated changes in knee-joint kinematics during landing. METHODS: Fifteen
      physically active male subjects performed drop jumps (30 and 50 cm) when
      nonfatigued and when fatigued. Whole-body fatigue was induced using a treadmill
      running protocol that incrementally increased effort. Peak-impact acceleration
      was measured with an accelerometer attached to the proximal tibia. Knee-joint
      kinematics were assessed during the eccentric phase: angle at initial touch down,
      maximum angle of flexion, range of motion, and peak angular velocity. RESULTS:
      Fatigue caused a significant increase in tibial impact acceleration and peak
      angular velocity in drop jumps from 30 cm (154.9 +/- 93.8 vs 192.6 +/- 103.9 m x
      s(-2): 24%; 675.3 +/- 60.7 vs 811.4 +/- 68.9 degrees x s(-1): 20%), but not from
      50 cm (222.4 +/- 74.9 vs 234.1 +/- 83.9 m x s(-2): 5%; 962.0 +/- 189.0 vs 984.4
      +/- 189.3 degrees x s(-1): 2.6%), with no associated change in the knee-joint
      angles assessed. It was argued, however, that rather than the neuromuscular
      system being selectively affected by fatigue at 30 cm and not 50 cm, drop jumps
      from 50 cm resulted in larger-impact accelerations with the neuromuscular system
      having only a limited ability to attenuate them per se, whether fatigued or
      nonfatigued. CONCLUSION: Care should be taken when performing drop jumps from a
      height of 30 cm in a fatigued state because of the reduced capacity to attenuate
      impact accelerations at the tibia, which may be associated with an increased risk
      of injury.

PMID- 17019308
TI  - Fast unilateral isometric knee extension torque development and bilateral jump
      height.
AB  - PURPOSE: We hypothesized that the initial rate (first 40 ms) of unilateral knee
      extensor torque development during a maximally fast isometric contraction would
      depend on the subjects' ability for fast neural activation and that it would
      predict bilateral jumping performance. METHODS: Nine males (21.8 +/- 0.9 yr,
      means +/- SD) performed unilateral fast isometric knee extensions (120 degrees
      knee angle) without countermovement on a dynamometer and bilateral squat jumps
      (SJ) and countermovement jumps (CMJ) starting from 90 and 120 degrees knee angles
      (full extension = 180 degrees ). The dynamometer contractions started either from
      full relaxation or from an isometric pre-tension (15% maximal isometric torque,
      Tmax). Torque time integral for the first 40 ms after torque onset (TTI-40,
      normalized to Tmax) and averaged normalized rectified knee extensor EMG for 40 ms
      before fast torque onset (EMG-40) were used to quantify initial torque rise and
      voluntary muscle activation. RESULTS: TTI-40 without pre-tension (range: 0.02
      0.19% Tmax per second) was significantly lower than TTI-40 with pre-tension, and
      both were significantly (r = 0.81 and 0.80) related to EMG-40. During jumping,
      similar significant positive relations were found between jump height and knee
      extensor EMG during the first 100 ms of the rise in ground reaction force. There
      also were significant positive linear relations between dynamometer TTI-40 and
      jump height (r = 0.75 (SJ 90), 0.84 (SJ 120), 0.76 (CMJ 90), and 0.86 (CMJ 120))
      but not between dynamometer Tmax and jump height (-0.16 < r < 0.02). CONCLUSION:
      One-legged TTI-40 to a large extent explained the variation in jump height. The
      ability to produce a high efferent neural drive before muscle contraction seemed
      to dominate performance in both the simple single-joint isometric task and the
      complex multijoint dynamic task.

PMID- 17019309
TI  - Contribution of the legs to double-poling performance in elite cross-country
      skiers.
AB  - PURPOSE: In the classical style of cross-country skiing, the double-poling (DP)
      technique, which is regarded as an upper-body exercise, is used on the flatter
      parts of a course. Limited biomechanical and physiological data are available
      about DP compared with other cross-country skiing techniques. The purpose of the
      present study was to evaluate the possible role of the lower body during DP.
      METHODS: Eleven elite cross-country skiers performed two incremental tests using
      DP roller skiing at 1 degree inclination on a treadmill with or without locking
      the knee and ankle joints (DPLOCKED and DPFREE). Maximal and peak oxygen uptake
      (VO2max and VO2peak) during classic diagonal skiing and DP, respectively, were
      measured. In addition, heart rate, blood lactate concentration, and maximal DP
      velocity (Vmax) were determined. Pole-ground reaction forces and joint angles
      (elbow, hip, knee, and ankle) were analyzed. RESULTS: The skiers obtained 7.7%
      higher VO2peak, 9.4% higher Vmax, and 11.7% longer time to exhaustion during
      DPFREE compared with DPLOCKED (all P < 0.05). There was a higher heart rate and
      blood lactate concentration in DPLOCKED at submaximal stages (all P < 0.05), with
      no difference in oxygen consumption. At 85% Vmax, corresponding to approximately
      81% VO2peak FREE, the differences in physiological variables were accompanied by
      a 13.6% higher poling frequency, a 4.9% shorter poling phase, 13.3% shorter
      recovery phase, and 10.9% lower relative pole force in DPLOCKED (all P < 0.05).
      CONCLUSIONS: Movements of the knee and ankle joints are an integrative part in
      the skillful use of the DP technique, and restriction of the motion in these
      joints markedly affects both biomechanical and physiological variables, impairing
      DP performance.

PMID- 17019312
TI  - Timely Tequin warning.

PMID- 17019320
TI  - Saving the skin during kinetic bed therapy.

PMID- 17019321
TI  - Mumps makes a comeback.

PMID- 17019325
TI  - Picking up the PACE: a new template for shift report.

PMID- 17019326
TI  - Using an infusion pump safely.

PMID- 17019327
TI  - What you need to know about genital herpes.

PMID- 17019328
TI  - Myths and facts...about polymyalgia rheumatica.

PMID- 17019343
TI  - Keep venous thromboembolism at bay.

PMID- 17019345
TI  - Patient education series. Deep vein thrombosis (DVT).

PMID- 17019346
TI  - Finding the right words.

PMID- 17019347
TI  - Nursing 2006 salary survey.

PMID- 17019348
TI  - Looking at liver cancer.

PMID- 17019349
TI  - Wearing personal protective gear.

PMID- 17019350
TI  - Managing the ups and downs of bipolar disorder.

PMID- 17019355
TI  - Skin care team improves assessment and documentation.

PMID- 17019356
TI  - Sleep aids: are you getting enough rest?

PMID- 17019358
TI  - ACLS challenge.

PMID- 17019357
TI  - Gauging fluid balance with osmolality.

PMID- 17019359
TI  - Combination drugs...

PMID- 17019360
TI  - Traumatic amputation.

PMID- 17019361
TI  - Genotype and phenotype patterns of drug-resistant HIV-1 subtype B' (Thai B)
      isolated from patients failing antiretroviral therapy in China.
AB  - Many AIDS patients in China who received free-of-charge antiretroviral
      therapeutics, including nucleoside reverse transcriptase inhibitors (NRTIs) and
      nonnucleoside reverse transcriptase inhibitors (NNRTIs), showed significant life
      improvement. Increasing numbers of patients, however, are experiencing
      antiretroviral therapy failure due to the emergence of drug-resistant viruses.
      The aim of this study was to investigate the genotypic and phenotypic drug
      resistance patterns of HIV-1 subtype B' variants, which are prevalent in China,
      in order to rationally design more efficient anti-HIV-1 regimens for future
      treatment of AIDS patients. 13 out of 16 patients (81%) who were treated with two
      NRTIs (ddI, and d4T or AZT) and one NNRTI (NVP) exhibited high resistance to NVP,
      8 of them with a >1,000 IC50 fold increase. Five codons (101, 103, 108, 181, and
      190) were involved in the NVP-resistant mutations, and K103N and Y181C mutations
      were predominant in these isolates. Fifteen isolates were resistant to at least
      one of the NRTIs, with high resistance to AZT (>10 IC50 fold increase) and
      intermediate resistance to d4T or ddI (approximately 4 IC50 fold increase). More
      than 10 codons were involved in the NRTI-resistant mutation and located in two
      regions (M41-V75 and T215-K219) of the reverse transcriptase. Concordance between
      the genotype and phenotype patterns for both NRTIs and NNRTI were detected in a
      majority of the isolates, suggesting that phenotypic resistance is predictable
      from genotyping assays, which are faster and less expensive than phenotypic
      assay. Because NVP and AZT can induce high resistances in these patients, these
      two drugs should be replaced with others more effective NNRTIs and NRTIs.

PMID- 17019362
TI  - Measuring the outcomes of a comprehensive HIV care course: pilot test at the
      Infectious Diseases Institute, Kampala, Uganda.
AB  - OBJECTIVE: To evaluate the effects of the Infectious Diseases Institute's 4-week
      course for African doctors on comprehensive management of HIV including
      antiretroviral therapy on four outcomes: (1) clinical skills, (2) clinical
      activities, (3) monitoring of HIV patients, and (4) training activities DESIGN:
      Clinical exam at beginning and end of course and at follow-up 3 to 4 months
      later, and a cross-section telephone survey. METHODS: Forty-seven doctors
      attending the course (October 2004, November 2004, March 2005, and April 2005)
      agreed to participate. A 17-item Clinical Exam Checklist was used to assess
      clinical skills. A telephone survey was conducted 1 month after the course to
      collect data in four areas: clinical activities, monitoring of HIV patients, case
      studies on initiation of ART, and training activities. RESULTS: The course
      improved the clinical skills of doctors. Between the beginning and end of the
      course, their clinical skills improved significantly in 11 of 17 areas (n = 34).
      Between the end of the course and follow-up, their skills improved significantly
      in three areas (n = 14). The trainees were practicing HIV care and training. The
      telephone survey (n = 46) showed that 93% of trainees treated HIV patients, 35%
      provided training on HIV, and 47% monitored the weight of the last HIV patient
      treated (patient's weight was a clinical end point to measure health status). At
      follow-up, everyone provided training and trained an average of 20 people per
      month.

PMID- 17019363
TI  - Novel approach for differential diagnosis of HIV infections in the face of
      vaccine-generated antibodies: utility for detection of diverse HIV-1 subtypes.
AB  - Because increasing numbers of HIV vaccine candidates are being tested globally,
      it is essential to differentiate vaccine- from virus-induced antibodies. Most of
      the currently tested vaccines contain multiple viral components. As a result,
      many vaccine recipients give positive results in FDA-licensed HIV serodetection
      tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are
      recognized soon after infection but are not included in most HIV vaccine
      candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established
      that distinguishes between vaccine-induced antibodies and seroconversion due to
      true HIV infections. It is important to make this assay globally relevant,
      because many clinical trials are conducted around the world where most HIV
      infections are due to non-B subtype HIV-1. Therefore, the current study examined
      the reactivity of plasma samples from >3,000 infections with diverse HIV subtypes
      worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both
      recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs
      were detected. Antibodies elicited by other vaccinations or infections endemic to
      the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST
      could be an important differential diagnostic tool for HIV vaccine trials, blood
      banks, and population screening worldwide.

PMID- 17019364
TI  - South Africa's "rollout" of highly active antiretroviral therapy: a critical
      assessment.
AB  - The number of people on highly active antiretroviral therapy (HAART) in South
      Africa has risen from < 2000 in October 2003, to almost 200,000 by the end of
      2005. Yet South Africa's performance in terms of HAART coverage is poor both in
      comparison with other countries and the targets set by the government's own
      Operational Plan. The public-sector HAART "rollout" has been uneven across South
      Africa's nine provinces and the role of external assistance from NGOs and funding
      agencies such as the Global Fund and PEPFAR has been substantial. The National
      Treasury seems to have allocated sufficient funding to the Department of Health
      for a larger HAART rollout, but the Health Minister has not mobilized it
      accordingly. Failure to invest sufficiently in human resources--especially nurses
      -is likely to constrain the growth of HAART coverage.

PMID- 17019365
TI  - Male circumcision in Siaya and Bondo Districts, Kenya: prospective cohort study
      to assess behavioral disinhibition following circumcision.
AB  - BACKGROUND: Evidence for efficacy of male circumcision as an HIV prevention
      measure is increasing, but there is serious concern that men who are circumcised
      may subsequently adopt more risky sexual behaviors. METHODS: Using a prospective
      cohort study, we compared sexual behaviors of 324 recently circumcised and 324
      uncircumcised men at 1, 3, 6, 9, and 12 months after circumcision/study
      enrollment. The main outcome indicators were incidence of sexual behaviors known
      to place men at increased risk of acquiring HIV, namely, having sex with partners
      other than their wife/wives for married men or other than "regular" girlfriends
      for unmarried men. RESULTS: During the first month following circumcision, men
      were 63% and 61% less likely to report having 0 to 0.5 and >0.5 risky sex
      acts/week, respectively, than men who remained uncircumcised. This difference
      disappeared during the remainder of follow-up, with no excess of reported risky
      sex acts among circumcised men. Similar results were observed for risky
      unprotected sex acts, number of risky sex partners, and condom use. DISCUSSION:
      During the first year post-circumcision, men did not engage in more risky sexual
      behaviors than uncircumcised men, suggesting that any protective effect of male
      circumcision on HIV acquisition is unlikely to be offset by an adverse behavioral
      impact.

PMID- 17019367
TI  - Performance of immunologic responses in predicting viral load suppression:
      implications for monitoring patients in resource-limited settings.
AB  - BACKGROUND: World Health Organization (WHO) guidelines for the use of
      antiretroviral therapy (ART) in resource-limited settings state that CD4 cell
      counts may be used to indicate when ART regimens should be changed because of
      treatment failure. The performance of immunologic monitoring for this purpose has
      not been evaluated, however. METHODS: Participants aged > or =18 years from the
      British Columbia HIV/AIDS Drug Treatment Program who had CD4 cell counts < or
      =200 cells/microL or an AIDS diagnosis at baseline had CD4 cell counts measured
      at 6 and 12 months after treatment initiation. Logistic regression analysis was
      used to calculate sensitivity, specificity, and positive and negative predictive
      values for immunologic responses in terms of predicting failure to achieve 2
      viral load measurements < 500 copies/mL within 1 year. RESULTS: Viral load
      suppression occurred in 674 (60%) of 1125 subjects. Using no increase in CD4 cell
      counts at 6 months as a definition of treatment failure had a sensitivity of 34%,
      specificity of 94%, positive predictive value of 75%, and negative predictive
      value of 71% for predicting failure to achieve virologic suppression. Using 12
      month CD4 cell count values, the measurements were 35%, 95%, 79%, and 73%,
      respectively. CONCLUSION: Immunologic criteria to predict which patients have not
      achieved virologic suppression results in significant misclassification of
      therapeutic responses.

PMID- 17019368
TI  - Downregulation of CCR5 expression on cells by recombinant adenovirus containing
      antisense CCR5, a possible measure to prevent HIV-1 from entering target cells.
AB  - Chemokine (C-C motif) receptor 5 (CCR5) is one of the major co-receptors for the
      macrophage (M)-tropic HIV-1. To prevent HIV-1 from entering into target cells, we
      inhibited CCR5 expression on target cell surface by recombinant adenovirus
      containing anti-sense CCR5 cDNA. A fragment of 653 bp cDNA located in the 5'
      region of CCR5 cDNA was reversely inserted into pAdTrack-CMV. Recombinant
      adenovirus containing antisense CCR5 cDNA (Ad-antiR5) was obtained by homologous
      recombination of resultant plasmid with the adenoviral backbone plasmid pAdEasy-2
      in E. coli BJ5183 and then packed in AD-293 cells. Rate of positive CCR5 on U937
      cell surface measured by flow cytometry was decreased from 89.53% to 1.88% after
      U937 cells infected with Ad-antiR5 for 24 hours, and this reduction lasted at
      least for 10 days. After challenged with HIV-1, the U937 cells infected with Ad
      antiR5 produced much less p24 antigen in cultured medium than those infected with
      control recombinant adenovirus and the uninfected cells. The recombinant
      adenovirus had no effect on chemotactic activity and proliferation of the U937
      cells. Therefore, the recombinant adenovirus containing anti-sense CCR5 cDNA can
      down-regulate CCR5 expression on U937 cells and protect the cells from HIV-1
      infection without effects on their chemotaxis activity and proliferation
      function.

PMID- 17019369
TI  - HIV prevalence and predictors among rescued sex-trafficked women and girls in
      Mumbai, India.
AB  - OBJECTIVE: Despite the rapid spread of India's HIV epidemic through commercial
      sex and the large numbers of minor girls trafficked to India for sex work each
      year, little HIV research has been conducted among victims of sex trafficking.
      The present study examines the prevalence and predictors of HIV infection among
      sex-trafficked women and girls rescued from brothels in Mumbai, India. DESIGN AND
      METHODS: Case records and HIV testing results of sex-trafficked women and girls
      (N = 175) were reviewed. HIV prevalence and HIV risk were assessed based on
      demographics and exposure to sex work. RESULTS: Approximately one quarter (22.9%)
      of trafficked individuals tested positive for HIV. The mean age at trafficking
      was marginally younger for women and girls infected with HIV (15.9 years) as
      compared to those not infected (17.2 years; P = 0.06). Girls trafficked as minors
      reported longer periods of brothel confinement as compared to those trafficked at
      older ages (18.5 vs. 9.6 months; P = 0.007). Among Indian victims, those
      trafficked from the states of Karnataka or Maharashtra were more likely than
      those trafficked from West Bengal to be HIV-positive (odds ratio [OR] = 7.35, 95%
      confidence interval [CI]: 2.23 to 24.21). Longer duration in brothels was
      associated with greater likelihood of HIV infection; a 3% to 4% increased risk
      for HIV was observed for each additional month of brothel captivity. CONCLUSIONS:
      Findings demonstrate the need for increased attention to HIV among young victims
      of sex trafficking in research and practice, and to the rescue of sex trafficking
      victims as a form of HIV prevention.

PMID- 17019370
TI  - Characteristics of recently HIV-infected men who use the Internet to find male
      sex partners and sexual practices with those partners.
AB  - OBJECTIVE: To examine (1) characteristics of recently HIV-infected men who have
      sex with men (MSM) who find sex partners through the Internet and (2) differences
      in characteristics of and sexual behaviors practiced with Internet partners as
      compared to other partner types. METHODS: From May 2002 to 2005, a computer
      assisted self-interview was administered to 194 recently HIV-infected MSM in
      southern California. MSM who used the Internet to find sex partners were compared
      with those who did not report Internet use, and partners found from the Internet
      were compared with those who were found from other venues using chi analyses, t
      tests, logistic regression, and generalized estimating equations. RESULTS:
      Seventy percent of participants reported using the Internet to find partners in
      the prior 3 months. In multivariate analysis, Internet users as compared to non
      Internet users reported higher education levels (some college vs. high school:
      odds ratio [OR] = 5.04; P < 0.01 and college or greater vs. high school: OR =
      9.61; P = 0.01), were more likely to be white (OR = 2.16; P = 0.04), reported
      more partners in the prior 3 months (OR = 1.05; P = 0.04), were more likely to
      have had sexual contact with all their last 3 partners after HIV diagnosis (OR =
      3.43; P < 0.01), and were more likely to report that all their last 3 partners
      were HIV-negative (OR = 3.35; P = 0.02), but none were main partners (OR = 2.36;
      P = 0.02). When compared with partners who were found in other venues, Internet
      partners were less likely to be main partners (OR = 0.52; P < 0.01) and were more
      likely to be younger (OR = 0.98; P = 0.05), to be HIV-negative (OR = 1.88; P =
      0.02), and to become sex partners after HIV diagnosis (OR = 1.58; P = 0.03).
      CONCLUSIONS: The Internet is a popular venue for recently HIV-infected MSM to
      find partners, many of whom are HIV-negative. Because finding sex partners
      through the Internet occurs after HIV diagnosis, the Internet could be a valuable
      target for new HIV prevention strategies.

PMID- 17019371
TI  - The ABCs of HIV prevention in men: associations with HIV risk and protective
      behaviors.
AB  - OBJECTIVE: To elucidate associations between beliefs in abstinence, fidelity, and
      condom use (the "ABCs" of preventing HIV and other sexually transmitted
      infections) and associated self-reported risk behaviors among Kenyan men.
      METHODS: We assessed associations of beliefs in the ABCs with sociodemographic
      characteristics and sexual risk behaviors in a respondent-driven sample of 500
      men in Nairobi. RESULTS: Younger age, single marital status, and higher education
      were associated with beliefs in abstinence and condom use as "best" prevention
      methods; and older age and marriage were associated with belief in fidelity. Many
      of these and other associations persisted in multivariate models. Men citing
      abstinence or fidelity belief less often reported sex with a female sex worker
      (FSW) ever or recent concurrent partnerships less often. Belief in fidelity was
      negatively associated with reported use of condoms ever. Belief in condom use to
      prevent HIV was most common among those having recent concurrent partnerships.
      CONCLUSIONS: Beliefs in abstinence, fidelity ("being faithful"), or condom use
      were associated, in plausible directions, with life stages and other demographic
      factors and with corresponding risk and preventive behaviors. Context-specific
      and selective educational promotion of individual ABC components rather than
      comprehensive education from an early age in a wide repertoire of prevention
      strategies ignores the evolution of sexual behaviors and the relative utility of
      different approaches throughout the life course.

PMID- 17019372
TI  - Same-sex behavior and high rates of HIV among men attending sexually transmitted
      infection clinics in Pune, India (1993-2002).
AB  - OBJECTIVES: To determine HIV/sexually transmitted infection (STI) prevalence,
      trends, and risk behaviors of men who have sex with men (MSM) and compare these
      with those of non-MSM attending STI clinics in Pune, India over a 10-year period.
      DESIGN: Cross-sectional. METHODS: From 1993 through 2002, men attending 3 STI
      clinics in Pune underwent HIV/STI screening. Demographic, risk behavior,
      clinical, and laboratory data were collected using standardized questionnaires
      and laboratory procedures. RESULTS: Of 10,785 men screened, 708 (6.6%) were MSM.
      Among these 708 MSM, 189 (31.7%) had 10 or more lifetime partners, 253 (35.7%)
      were married, 163 (23.1%) had sex with a hijra (eunuch), and 87 (13.3%) had
      exchanged money for sex. A total of 134 (18.9%) were HIV-positive, 149 (21.5%)
      had genital ulcer disease (GUD), 37 (5.8%) had syphilis, and 29 (4.3%) had
      gonorrhea (GC). Over the decade, neither HIV nor GC prevalence changed among MSM
      (P = 0.7), but syphilis and GUD decreased significantly (P < 0.0001). Compared
      with non-MSM, MSM were more likely to initiate sexual activity at age <16 years,
      to have >10 lifetime partners, to have sex with a hijra, and to use condoms
      regularly, but they did not differ significantly in HIV prevalence and had a
      lower prevalence of GC, GUD, and syphilis. Independent factors associated with
      HIV among MSM were employment (adjusted odds ratio [AOR] = 3.08; P = 0.02),
      history of GUD (AOR = 1.86; P = 0.003), and syphilis (AOR = 2.09; P = 0.05).
      CONCLUSIONS: Same-sex and high-risk sexual behaviors are prevalent among men
      attending STI clinics in India. Although syphilis and GUD rates decreased, HIV
      prevalence remained high during the decade, highlighting the importance of
      additional targeted efforts to reduce HIV risk among all men, including MSM, in
      India.

PMID- 17019373
TI  - Micronutrient levels and HIV disease status in HIV-infected patients on highly
      active antiretroviral therapy in the Nutrition for Healthy Living cohort.
AB  - BACKGROUND: Low serum micronutrient levels were common before widespread use of
      highly active antiretroviral therapy (HAART) and were associated with adverse
      outcomes. Few data are available on micronutrient levels in subjects taking
      HAART. OBJECTIVE: To determine the prevalence of low serum retinol, alpha
      tocopherol, zinc, and selenium in HIV-infected subjects taking HAART and to
      assess the association of micronutrient levels with HIV disease status. DESIGN:
      Cross-sectional. SETTING: Nutrition for Healthy Living (NFHL) study.
      PARTICIPANTS: HIV-infected subjects on HAART. METHODS: Retinol, alpha-tocopherol,
      zinc, and selenium were determined in frozen serum samples from 171 men and 117
      women. Low serum levels were defined as retinol <30 microg/dL, selenium <85
      microg/L, alpha-tocopherol <500 microg/dL, and zinc <670 microg/L. Association of
      micronutrient quartiles with CD4 cell count, CD4 count <200 cells/mm, HIV viral
      load (VL), and undetectable VL was assessed using adjusted multivariate
      regression. RESULTS: Five percent of men and 14% of women had low retinol, 8% of
      men and 3% of women had low selenium, and 7% of men and no women had low alpha
      tocopherol. Forty percent of men and 36% of women had low zinc, however. Subjects
      in the upper quartiles of zinc had lower log VL levels than those in the lowest
      quartile (significant for women). Subjects in the upper quartiles of selenium
      also tended to have lower VL levels compared with those in the lowest quartile.
      Surprisingly, women in the upper quartiles of retinol had higher log VLs than
      those in the lowest quartile. There was no significant association of any
      micronutrient with CD4 cell count or likelihood of CD4 count <200 cells/mm. The
      level of CD4 cell count influenced the association of retinol with log VL in men,
      however. In men with CD4 counts >350 cells/mm, those with higher retinol had
      higher log VLs compared with the lowest quartile, whereas in men with CD4 counts
      <350, those with higher retinol levels had lower log VLs compared with the lowest
      quartile. CONCLUSIONS: Low retinol, alpha-tocopherol, and selenium are uncommon
      in HIV-infected subjects on HAART. Zinc deficiency remains common, however.
      Decreased retinol levels in women and in men with CD4 counts >350 cells/mm and
      increased zinc and selenium levels in both genders may be associated with
      improved virologic control.

PMID- 17019374
TI  - An isopropanolic extract of black cohosh does not increase mammographic breast
      density or breast cell proliferation in postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to determine the effects of the
      isopropanolic extract of black cohosh (Remifemin) on mammographic breast density
      and breast epithelial proliferation in healthy, naturally postmenopausal women
      with climacteric symptoms. DESIGN: This was a prospective, open, uncontrolled
      drug safety study in which baseline status was compared with status after 6
      months of treatment by blinded observers. A total of 74 women were treated with
      40 mg black cohosh daily, and 65 women completed the study. Mammograms were
      performed, and breast cells were collected by percutaneous fine needle aspiration
      biopsies at baseline and after 6 months. Mammographic density was quantified
      according to the Wolfe classification or a percentage scale. Breast cell
      proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. Safety was
      monitored by adverse event reporting, laboratory assessments, and measurement of
      the endometrium by vaginal ultrasound. RESULTS: None of the women showed any
      increase in mammographic breast density. Furthermore, there was no increase in
      breast cell proliferation. The mean change +/- SD in proportion of Ki-67-positive
      cells was -0.5% +/- 2.4% (median, 0.0; 95% CI = -1.32 to 0.34) for paired
      samples. The mean change in endometrial thickness +/- SD was 0.0 +/- 0.9 mm
      (median, 0.0). A modest number of adverse events were possibly related to
      treatment, but none of these were serious. Laboratory findings and vital signs
      were normal. CONCLUSIONS: The findings suggest that the isopropanolic extract of
      black cohosh does not cause adverse effects on breast tissue. Furthermore, our
      data do not indicate to any endometrial or general safety concerns during 6
      months of treatment.

PMID- 17019375
TI  - Effect of soy protein-containing isoflavones on lipoproteins in postmenopausal
      women.
AB  - OBJECTIVE: Some clinical trials have demonstrated a beneficial effect of dietary
      soy protein on improving lipoproteins. Research also has documented that serum
      lipoproteins and some lipoprotein subclasses are altered as a consequence of
      menopause, resulting in a more atherogenic lipid profile. The purpose of this
      study was to determine the effects of isolated soy protein-containing isoflavones
      on lipoproteins and lipoprotein subclasses in both African American and white
      postmenopausal women with borderline to moderate low-density lipoprotein
      cholesterol elevations. DESIGN: This was a randomized, double-blind, controlled
      clinical trial including 216 postmenopausal women. After a 4-week run-in period
      with a casein protein-based supplement, participants were randomly assigned to
      continue the casein placebo or receive soy protein-containing isoflavones for a
      period of 12 weeks. RESULTS: In the soy group, the total cholesterol, low-density
      lipoprotein cholesterol, and low-density lipoprotein particle number decreased
      significantly as compared with the placebo group at 6 weeks. Although this
      decrease continued at 12 weeks in the soy group, the difference from the placebo
      group was attenuated for total cholesterol and low-density lipoprotein particle
      number. Multivariate analyses controlling for age, race, change in weight, change
      in dietary fat intake, and change in kilocalorie energy expenditure revealed that
      treatment remained a significant independent predictor of change in total
      cholesterol (P = 0.01), low-density lipoprotein cholesterol (P = 0.02), and low
      density lipoprotein particle number (P = 0.002) after 6 weeks of dietary soy.
      CONCLUSIONS: Increased consumption of soy protein replacing animal protein that
      is high in fat may help improve atherogenic lipid profiles.

PMID- 17019377
TI  - Time-related trends of age at menopause and reproductive period of women in a
      Chuvashian rural population.
AB  - OBJECTIVE: The objective of this study was to examine in an observational, cross
      sectional, community-based study the secular trend of age at menopause among
      women in a rural Chuvashian population and to identify factors associated with
      age at menopause. DESIGN: The sample included 316 postmenopausal women born
      between 1920 and 1950 with mean age at menopause of 48.47 +/- 4.63 (34-58) years.
      Statistical analyses included simple and multiple linear regression and
      "whiskers" plots. RESULTS: Significant association was found between year of
      birth and age at menopause (beta = 0.194, P < 0.001) and reproduction period (P =
      0.193, P < 0.001). Mean values of age at menopause increased from 47.0 years
      (born during 1920-1925) to maximal values of 49.7 years (born during 1940-1945)
      and 49.3 years (born during 1945-1950). Mean values of their reproductive period
      increased from 30.7 (born during 1920-1925) to maximal values of 34.1 (born
      during 1940-1945) and to 33.7 (born during 1945-1950). Multiple linear regression
      analysis demonstrated that year of birth was the only statistically significant
      (P = 0.19, P < 0.01) predictor of age at menopause. Age at menarche can also be a
      possible predictor of age at menopause (beta = -0.12, P = 0.04). CONCLUSIONS: The
      study confirmed certain secular trends of age at menopause and reproductive
      periods in Chuvashian women. The authors also observed a negative association
      between age at menarche and age at menopause. The number of children and medical
      abortions as well as body mass index showed no association with age at menopause.

PMID- 17019376
TI  - Evolving practice patterns and attitudes toward hormone therapy of obstetrician
      gynecologists.
AB  - OBJECTIVE: The objective of this study was to examine the opinions and
      prescribing practices of obstetrician-gynecologists regarding hormone therapy
      (HT) and the results from the Women's Health Initiative. DESIGN: Surveys were
      sent to 2,500 randomly selected American College of Obstetrics and Gynecology
      fellows during December 2004 to March 2005; their responses are compared with
      those from a survey conducted in November to December 2003. RESULTS: Respondents
      remained skeptical of the combined HT results (49.1% did not find the results
      convincing). Compared with the 2003 survey, men were more skeptical (58.8% did
      not consider the findings convincing in 2004 vs 53.4% in 2003, P = 0.045), and
      women were somewhat less skeptical (39.5% did not consider the findings
      convincing in 2004 vs 45.3% in 2003, P = 0.056). There was less skepticism about
      the estrogen-only trial, although 4 of 10 did not find the results convincing.
      Men were more skeptical than women; a majority of men disagreed with the
      decisions to stop the trials. Physicians who completed their residency more
      recently were more likely to accept the trial results. Respondents reported a
      reduction in HT prescription practice relative to the year 2000, but 62.7%
      reported they did not expect their prescribing practices to change further in the
      near future. The proportion of respondents who considered alternative therapies
      to HT as viable treatment options increased between 2003 and 2004 (37.1% vs
      28.1%, P < 0.001). There was strong support for the use of HT for vasomotor
      symptoms, vaginal dryness, and osteoporosis, but most physicians did not consider
      HT useful for cardiovascular disease or dementia. CONCLUSIONS: Many obstetrician
      gynecologists continue to express skepticism about the results and conduct of the
      Women's Health Initiative trials. The survey could not determine the reasons for
      skepticism.

PMID- 17019378
TI  - Menopause and determinants of quality of life in women at midlife and beyond: the
      study of health in pomerania (SHIP).
AB  - OBJECTIVE: Determinants of quality of life (QoL) in pre- and postmenopausal women
      including nonhormonal modulators of QoL in adult women are not well understood;
      there is an ongoing controversy about the impact of menopause on health-related
      QoL. We investigated the extent to which diverse mental and physical symptoms are
      associated with (a) menopausal status; (b) sociodemographic, psychosocial, and
      lifestyle factors; and (c) menopausal hormone therapy (MHT) in adult women after
      the German reunification in a region of the former German Democratic Republic.
      DESIGN: The Study of Health in Pomerania is a cross-sectional, population-based
      survey. Computer-based structured interviews and self-administered questionnaires
      were used to capture QoL (Zerssen Symptom List) and sociodemographic parameters,
      psychosocial, and lifestyle indicators (age, socioeconomic status, abuse, social
      support, nutrition, body mass index, self-rated health, chronic diseases, and use
      of MHT) in 1,119 pre- and postmenopausal women with an intact uterus. RESULTS:
      Analyses suggest that menopausal status was not associated with QoL. MHT was
      associated with physical, mental, and gastrointestinal symptoms. Age was a
      significant predictor for cardiopulmonary symptoms and sensory impairment. The
      relationship between age and both physical and mental complaints was inverse as
      was the relationship between age and both mood and gastrointestinal symptoms.
      Age, socioeconomic status, physical and sexual abuse, perceived social support,
      nutrition, body mass index, self-rated health, chronic diseases, and MHT
      modulated QoL. CONCLUSIONS: Our findings do not support the hypothesis that QoL
      is reduced after menopause. Differences between pre- and postmenopausal women can
      be explained by sociodemographic, psychosocial, and lifestyle factors.

PMID- 17019379
TI  - Monitoring reproductive aging in a 5-year prospective study: aggregate and
      individual changes in luteinizing hormone and follicle-stimulating hormone with
      age.
AB  - OBJECTIVE: This study describes age-related changes in luteinizing hormone (LH)
      and follicle-stimulating hormone (FSH) in a 5-year prospective study of
      reproductive aging. DESIGN: Participants (n = 156 college-educated, white, US
      women; 25 to 58 y) were recruited from the TREMIN Research Program on Women's
      Health. They collected daily urine specimens for 6 months in each of 5
      consecutive years. Specimens were assayed for LH and FSH. Aggregate changes were
      calculated in LH and FSH with age, and multilevel models were used to estimate
      individual hormone trajectories and within-woman and between-woman variances by
      age. RESULTS: Aggregate LH levels increased beginning after age 45; FSH increased
      at all ages, accelerating after age 45. Individual-level patterns with age
      included the following: reproductive-age LH and FSH levels, with increasing FSH
      and increasing or decreasing LH (ages 20 to 49); rapidly increasing LH and FSH
      (ages 40 to 59); and increasing or steady postmenopausal LH and FSH (ages 46 to
      62). FSH levels were consistently high in the latter category, but LH levels
      overlapped with levels found in younger women (<45 y). Individual LH patterns
      showed more variability (5% to 35% of total variance) than FSH (3% to 22% of
      total variance). Both hormones had relatively low variation within individuals
      compared with between-woman differences (65% to 97% of total variance).
      CONCLUSIONS: Aggregate-level data do not reflect differences across women and
      oversimplify the age-related increases and variability in LH and FSH. Individual
      FSH levels are not distinguishable from reproductive-age levels until after rapid
      perimenopausal increases in FSH occur; individuals vary in whether their
      postmenopausal LH levels are distinguishable from reproductive-age levels.

PMID- 17019380
TI  - Acupuncture for hot flashes: a randomized, sham-controlled clinical study.
AB  - OBJECTIVE: Hot flashes are a significant problem in women going through the
      menopausal transition that can substantially affect quality of life. The world of
      estrogen therapy has been thrown into turmoil with the recent results of the
      Women's Health Initiative trial report. Pursuant to a growing interest in the use
      of alternative therapies to alleviate menopausal symptoms and a few pilot trials
      that suggested that acupuncture could modestly alleviate hot flashes, a
      prospective, randomized, single-blind, sham-controlled clinical trial was
      conducted in women experiencing hot flashes. DESIGN: Participants, after being
      randomized to medical versus sham acupuncture, received biweekly treatments for 5
      weeks after a baseline assessment week. They were then followed for an additional
      7 weeks. Participants completed daily hot flash questionnaires, which formed the
      basis for analysis. RESULTS: A total of 103 participants were randomized to
      medical or sham acupuncture. At week 6 the percentage of residual hot flashes was
      60% in the medical acupuncture group and 62% in the sham acupuncture group. At
      week 12, the percentage of residual hot flashes was 73% in the medical
      acupuncture group and 55% in the sham acupuncture group. Participants reported no
      adverse effects related to the treatments. CONCLUSIONS: The results of this study
      suggest that the used medical acupuncture was not any more effective for reducing
      hot flashes than was the chosen sham acupuncture.

PMID- 17019381
TI  - Effects of soy germ isoflavones and hormone therapy on nitric oxide derivatives,
      low-density lipoprotein oxidation, and vascular reactivity in
      hypercholesterolemic postmenopausal women.
AB  - OBJECTIVE: To evaluate the effects of soy germ isoflavones and hormone therapy on
      vascular reactivity, the formation of nitric oxide derivatives, and lipid
      peroxidation in hypercholesterolemic postmenopausal women. DESIGN: Women were
      treated with soy germ, 17beta-estradiol or 17beta-estradiol + noretisterone
      acetate for 3 months after taking placebo for 1 month. The plasma concentrations
      of nitrite + nitrate and S-nitrosothiols were evaluated by gaseous phase
      chemiluminescence; nitrotyrosine, electronegative low-density lipoprotein, and
      estradiol levels were determined by enzyme-linked immunosorbent assay;
      cholesterol oxides and isoflavones were determined by gas chromatography and high
      performance liquid chromatography, respectively. Vascular reactivity was analyzed
      by high-resolution ultrasonography. RESULTS: Soy germ isoflavones and hormone
      therapy induced a decrease in nitrite + nitrate, electronegative low-density
      lipoprotein, and cholesterol oxides, as well as an increase in S-nitrosothiols.
      Soy germ isoflavones lowered electronegative low-density lipoprotein, and
      cholesterol oxides more efficiently than did hormone therapy. Only soy
      isoflavones inhibited nitrotyrosine formation. A significant improvement of
      vascular reactivity was only seen in women treated with 17beta-estradiol.
      CONCLUSIONS: The soy germ isoflavones and 17beta-estradiol, alone or associated
      with noretisterone acetate, in the doses and forms used here, have similar
      effects on the bioavailability of nitric oxide. Soy germ treatment inhibited
      lipid peroxidation more effectively than hormone therapy.

PMID- 17019382
TI  - Effects of ovarian failure and X-chromosome deletion on body composition and
      insulin sensitivity in young women.
AB  - OBJECTIVE: Menopause is associated with increased visceral adiposity and reduced
      insulin sensitivity. It remains unclear whether these changes are due primarily
      to ovarian failure or aging. The aim of this study was to clarify the impact of
      ovarian failure on body composition and insulin sensitivity in young women.
      DESIGN: In a cross-sectional study, we compared main outcome measures (body mass
      index, body composition by dual-energy x-ray absorptiometry, and insulin
      sensitivity by Quantitative Insulin Sensitivity Check Index) in three groups:
      women with 46,XX premature ovarian failure (POF), women with premature ovarian
      failure associated with 45,X or Turner syndrome (TS), and normal control women
      (NC). Participants were enrolled in National Institutes of Health Clinical Center
      protocols between years 2000 and 2005. RESULTS: Mean body mass index (+/- SD) was
      lower in women with POF (n = 398): 24.3 +/- 5 kg/m versus 27.8 +/- 7 for women
      with TS (n = 131) and 26.6 +/- 4 for controls (n = 73) (both P < 0.001). Only 33%
      of women with POF were overweight or obese, compared with 56% of those with TS
      and 67% of NC women (P < 0.0001 for both). Despite less obesity, women with POF
      had lower insulin sensitivity (0.367 +/- 0.03) compared with those with TS (0.378
      +/- 0.03, P = 0.003) and NC women (0.376 +/- 0.03, P = 0.04). In groups selected
      for similar age and body mass index, women with POF (n = 89), women with TS (n =
      48), and NC women (n = 40) had similar total body and trunk adiposity. After
      adjustment for age and truncal adiposity, women with POF had significantly lower
      insulin sensitivity than women with TS (P = 0.03) and NC women (P = 0.049).
      CONCLUSIONS: In contrast to observations in middle-aged postmenopausal women,
      ovarian failure in young women is not associated with increased total or central
      adiposity. In fact, women with TS were similar to NC women, whereas women with
      POF were leaner. The lower insulin sensitivity observed in women with POF
      deserves further investigation.

PMID- 17019383
TI  - The new look of bedside technology. The point-of-care evolution drives providers
      to rethink nursing workflow and medication management.

PMID- 17019384
TI  - Do the math: Staffing software multiplies effectiveness. Count your options for
      simplifying staff management.

PMID- 17019385
TI  - Master planning bridges gaps. No department is an island. Selecting and
      integrating healthcare technology must be a collaborative process.

PMID- 17019386
TI  - Passage of mannitol into the brain around gliomas: a potential cause of rebound
      phenomenon. A study on 21 patients.
AB  - AIM: Widespread use of mannitol to reduce brain edema and lower elevated ICP in
      brain tumor patients continues to be afflicted by the so-called rebound
      phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB
      and secondary reversal of osmotic gradient is considered the major cause of
      rebound . This has only been demonstrated experimentally in animals. As a
      contribution to this issue we decided to research the possible passage of
      mannitol into the brain after administration to 21 brain tumor patients. METHODS:
      Mannitol (18% solution; 1 g/kg) was administered as a bolus to patients (ten had
      malignant glioma, seven brain metastases and four meningioma) about 30 minutes
      before craniotomy. During resection, a sample of the surrounding edematous white
      matter was taken at the same time as a 10 ml venous blood sample. Mannitol
      concentrations were measured in plasma and white matter by a modified version of
      the enzyme assay of Blonquist et al. RESULTS: In most glioma patients, mannitol
      concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5
      times). In meningioma and metastases patients plasma concentrations of mannitol
      were higher than white matter concentrations except in three cases with
      infiltration by neoplastic cells. CONCLUSIONS: The results of our study show that
      even after a single bolus, mannitol may leak through the altered BBB near
      gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating
      peritumoral edema and promoting rebound of ICP.

PMID- 17019387
TI  - Chronic expanding intracerebral hematoma treated by mini-invasive ultrasonography
      guided needle aspiration.
AB  - Chronic expanding intracerebral hematoma (CEIH) is a rare cerebrovascular disease
      that behaves as a slowly expanding lesion with a gradual onset of progressive
      neurological deficit or recurrent seizures. The etiology of the CEIH is still not
      clear. Even if about a half of these lesions are associated with vascular
      malformations, the remaining cases are post-traumatic, associated with
      coagulative disorders or are cryptogenic. Treatment of these lesions is
      controversary: while some neurosurgeons remove the hematoma with its capsule,
      others prefer to wait and observe it if the patient is neurologically stable. We
      discuss the opportunity of treating selected patients bearing a CEIH by means of
      ultrasonography(US)-guided aspiration in selected patients. A 42-year-old
      hepatopathic man with coagulation disorders was referred to us with a 2-month
      history of progressive right-sided weakness, speech disorders and difficulty in
      swallowing solid foods. Radiological findings supported a CEIH with a thin
      surrounding capsule. The patient underwent to US-guided aspiration of the lesion
      with a complete resolution of the hematoma, confirmed intraoperatively by real
      time US-control and postoperatively by early and long term neuroradiological
      controls. US-guided aspiration is a low cost, not time consuming technique, that
      allows an intraoperative real-time control of the lesion and seems to be an
      effective alternative to open surgery in cases of CEIHs with a thin capsule.

PMID- 17019388
TI  - Contralateral development of chronic subdural hematoma after evacuation of
      chronic subdural hematoma. A case report.
AB  - Contralateral acute complications such as acute epi/subdural hematomas can be
      encountered after evacuation of a chronic subdural hematoma, though they are
      rare. We found only one case of chronic subdural hematoma following the surgery
      for contralateral chronic subdural hematoma, have been published in English
      language literature. A 73-year-old male admitted to our hospital with a right
      sided subdural hematoma. The subdural hematoma was evacuated through a burr-hole.
      A left-sided subdural higroma appeared after operation and turned into classical
      subdural hematoma in the course of time. After evacuation of contralateral
      chronic subdural hematoma, the patient recovered completely. All stages of the
      development of contralateral chronic subdural hematomas were shown by serial
      computed tomograms. It was suggested that traumatic chronic subdural hematomas
      develop from mostly subdural higromas. If contralateral subdural higroma is seen
      after surgical evacuation of a chronic subdural hematoma, the possibility of
      development of contralateral chronic subdural hematoma must be kept on mind.

PMID- 17019389
TI  - Cervical anterior hyperostosis: a rare cause of dysphagia. Report of 3 cases.
AB  - Disorders of the cervical spine rarely cause dysphagia and/or dysphonia.
      Exuberant osteophytosis, secondary to diffuse idiopathic skeletal hyperostosis,
      also referred to as Forestier's disease, seems to be the predominant cause.
      Forestier's disease is a non inflammatory enthesopathy, of unknown etiology,
      ossifying the anterior longitudinal ligament of the spine, sparing the discs, and
      usually affecting older men. We describe the successful surgical treatment of 3
      cases, over the course of 26 years, observed in our Neurosurgical Unit.

PMID- 17019390
TI  - Arachnoid cyst mimicking normal pressure hydrocephalus. A case report and review
      of the literature.
AB  - A case of a 61-year-old female patient who presents with the clinical triad of
      normal pressure hydrocephalus (NPH), abnormal gait, urinary incontinence and
      dementia. On CT scanning, she is found to have a large arachnoid cyst which
      mimicked the syndrome of NPH. This is also the 60th published case of arachnoid
      cyst presenting over the age of 60.

PMID- 17019391
TI  - Drug-eluting stents: towards new endpoints.
AB  - Drug-eluting stents (DES) have significantly reduced the rates of in-stent
      restenosis (ISR). As previously observed with bare-metal stents (BMS), either
      patient's clinical characteristics and lesion morphology may influence the risk
      of recurrence even with DES. In this review we will focus on the most recent
      available data on clinical settings where DES efficacy on long-term outcomes are
      largely unknown. In particular, we report on very complex lesions (bifurcations,
      small vessels, chronic total occlusions, in-stent restenosis) myocardial
      infarction, multivessel disease, treatment of bypass graft and of unprotected
      left main disease. Several issues are still open on DES routinary use for these
      indications, mainly as far as stent thrombosis is concerned. Recent pathological
      studies show that DES are characterized by chronic inflammatory infiltrates and
      delayed endothelialization. Therefore, this effect could translate in a
      ''vulnerable period'' for thromboses longer than with BMS. Even though large meta
      analysis have excluded higher rates of stent thrombosis with DES rather than with
      BMS, few cases of unusual very late stent thrombosis have been described,
      pointing out that this problem seems to be still unsolved. Although DES provide
      better angiographic outcomes in each clinical setting, further randomized studies
      are running to assess their safety and efficacy on currently off-label
      indications.

PMID- 17019392
TI  - Clinical evidence on polymer-based sirolimus and paclitaxel eluting stents.
AB  - Percutaneous coronary interventions with the use of stents have become the
      mainstay treatment of patients with various clinical manifestations of coronary
      artery disease. Despite their remarkable success, restenosis has remained the
      major drawback and its prevention has absorbed intensive experimental and
      clinical research work. After the failure of multiple efforts with systemic use
      of various drugs, local application of antiproliferative and anti-inflammatory
      agents released by specially designed coated stents led to considerable
      suppression of neointima and opened new prospects in the prevention of
      restenosis. An increasing body of evidence is showing the advantages provided by
      drug-eluting stents (DES) in almost all subsets of patients with coronary artery
      disease with a drastic decrease in the need for reintervention. To date, the most
      commonly used and the only US Food and Drug Administration (FDA) approved DES are
      a sirolimus-eluting stent (Cypher) and a paclitaxel-eluting stent (Taxus), both
      of which are polymer-based DES and will constitute the focus of this review.
      Recent data demonstrate that DES are not equal in their safety and efficacy. A
      less optimistic aspect of DES technology are the reiterated concerns about a more
      prolonged risk of stent thrombosis. Although all agree on the need of a longer
      duration of dual antiplatelet therapy in patients treated with DES, its optimal
      length is still to be defined. Because polymers used for stent coating are often
      seen at the origin of the compromised long-term safety of DES, new technologies
      able to avoid permanent polymers may offer a valuable alternative.

PMID- 17019393
TI  - How to treat diabetic patients with multivesseal disease in the DES era.
AB  - Patients with type 2 diabetes mellitus represent the 25% of those requiring
      myocardial revascularization. Choice of treatment in diabetic patients is much
      more controversial than in non-diabetics: this because coronary artery disease is
      more often complex and diffuse, left ventricular function is depressed, and
      concomitant multiple risk factors are present. These subset of patients
      experience worse outcomes than non diabetic patients undergoing either coronary
      artery bypass grafting (CABG) or percutaneous coronary interventions (PCI). Large
      randomized trials performed both in the early era of PCI and in the stent era
      suggest that CABG is superior to bare metal stent implantation in the treatment
      of diabetic patients with multivessel coronary artery disease. These findings are
      reflected in current guidelines, which favor CABG over PCI in most diabetics who
      require revascularization. However, substantial variability exists in practice
      patterns among individual hospital, suggesting a lack of clinical consensus. The
      major advantage of CABG over bare metal stent implantation in diabetic patients
      is the lower risk of repeat revascularization procedures through the follow-up.
      Better angiographic results have been demonstrated in the new era of drug-eluting
      stents (DES). Data from both the sirolimus and paclitaxel-eluting stents trials
      support the potential advantage of DES implantation both in diabetic and non
      diabetic patients. Preliminary data from studies comparing DES versus CABG in
      diabetic patients with multivessel coronary artery disease suggests that 1) no
      significant difference exists in the 12-month rate of death, myocardial
      infarction and cerebrovascular events in patients treated with DES as compared to
      off-pump bypass surgery, 2) a difference of 7.1% in the rate of repeat
      revascularization at 12-month exists in favor of bypass surgery and 3) diabetic
      retinopathy identifies a subgroup with poor outcome after both percutaneous and
      surgical myocardial revascularization.

PMID- 17019394
TI  - How to approach drug-eluting stent restenosis.
AB  - Drug-eluting stents (DES) have been a major advance in percutaneous coronary
      intervention reducing restenosis and repeat revascularization. The application of
      DES to the treatment of complex lesion and patient subsets has resulted in
      significant rates of DES restenosis or failure. Though predominantly focal,
      substantial rates of non-focal DES restenosis are being observed. Non-focal
      disease most likely represents a resistant process that will remain a therapeutic
      challenge. An understanding of the causative mechanical and biological factors is
      essential for the prevention and treatment of DES restenosis. Robust data
      relating to the treatment efficacy for this problem is lacking. At present,
      repeat DES or vascular brachytherapy appear to the best available options.
      Evidence from randomized controlled trials and large registries is required to
      establish a formal treatment approach. We provide guidelines based on current
      available evidence.

PMID- 17019395
TI  - Percutaneous treatment of coronary bifurcation lesions in the era of drug-eluting
      stents.
AB  - The current report provides an overview of the evolving techniques for
      percutaneous treatment of bifurcation lesions, including the approaches most
      commonly used in the current era of DES, and reviews the angiographic and
      clinical outcomes from clinical series published to date.

PMID- 17019396
TI  - Coronary calcification in cardiovascular risk stratification.
AB  - The correlation between coronary calcifications and subclinical atherosclerotic
      disease has been well known for some years now. Today we are able to quantify
      coronary calcium deposits, the calcium score, by means of new imaging techniques
      such as electron beam computed tomography and multislice spiral computed
      tomography. A large number of studies performed using these methods has confirmed
      the association between coronary calcifications and atherosclerotic disease and
      has opened up the possibility of early diagnosis of any subclinical
      atherosclerotic disease in various subpopulations such as diabetics and
      nephropatics. The etiopathogenesis of coronary calcium has not yet been made
      clear; it appears to be an active process similar to bone formation that involves
      cells similar to those involved in the reabsorption of bone matrix. The calcium
      score, therefore, provides physicians with a further diagnostic tool able to
      better determine cardiovascular risk patients and supplements the Framingham risk
      score. International guidelines have not yet illustrated with any precision in
      which ambits to apply screening for the quantification of coronary calcium and
      consequently, for the time being, the use of such methods must be restricted to
      cases in which the possibility of any benefit can be scientifically shown. This
      review represents the state of the art on coronary calcification and its role in
      clinical practice.

PMID- 17019397
TI  - Invasive imaging techniques for the assessment of vulnerable plaque.
AB  - Coronary artery disease is the leading cause of mortality and morbidity in the
      Western world and an ever-increasing problem in developing countries. Unheralded
      acute coronary syndromes (ACS) are common initial manifestations of coronary
      atherosclerosis and are often caused by lesions which have previously not
      generated symptoms. Histopathological studies have identified several plaque
      morphologies associated with ACS. However, the natural history of these high-risk
      or vulnerable lesions remains unknown and the limited knowledge about their
      eventual prognosis is provided by retrospective histopathological studies.
      Detection of these vulnerable plaques in vivo is essential to study their natural
      history and to evaluate potential treatment modalities and, therefore, may
      ultimately have an important impact on the prevention of acute myocardial
      infarction and death. Currently, there are several diagnostic imaging tools
      capable of evaluating determinants of plaque vulnerability. These techniques can
      provide information on the vessel lumen and wall size, tissue composition and the
      status of inflammation. This article aims to review the current status of these
      imaging techniques.

PMID- 17019398
TI  - Noninvasive imaging of the coronary arteries.
AB  - A reliable noninvasive imaging method for significant coronary artery stenosis
      would have enormous implications related to cost of diagnosis and enhanced
      patient safety. Cardiac motion and calcified plaques, in the past, rendered a
      substantial number of computed tomographic (CT) images of the coronary arteries
      uninterpretation. The accuracy of multidetector CT for the detection of coronary
      stenosis appears to have progressively improved as the imaging equipment
      increased from 4-slice and 16-slice to 64-slice CT. With 64-slice CT, scanning of
      the entire coronary artery tree is possible in 10 to 13 s. Pooled data of results
      of a few investigations with 64-slice CT showed that the proportion of
      unevaluable segments is only 4%. The sensitivity of 64-slice CT for the detection
      of significant (>50% or = or >50%) coronary stenosis in a patient, based on
      pooled data, was 97% and specificity was 91%. Regarding detection of significant
      stenosis in any segment, the sensitivity, based on pooled data, was 91% with 64
      slice CT and specificity was 96%. In a limited number of patients, sensitivity
      for detection of significant stenoses in proximal segments was 100%, in mid
      segments it was 94%, and in distal segments sensitivity it was 80%. Multi
      detector CT provides the opportunity to quantify non-calcified coronary artery
      plaques, which may potentially be a strong predictor of cardiac events. It was
      also shown to be useful for the detection of stenosis in coronary artery bypass
      grafts.

PMID- 17019399
TI  - Percutaneous coronary intervention in unprotected left main disease: a status
      report.
AB  - Percutaneous coronary intervention (PCI) of the unprotected left main (LM) artery
      is currently not recommended as a routine procedure based on the history of
      inferior outcomes of LM percutaneous transluminal coronary angioplasty and bare
      metal stenting. Instead, surgical revascularization (coronary artery bypass
      grafting, CABG) is considered to be the gold standard. There is renewed interest
      in LM-PCI because of improved outcomes of PCI utilizing drug eluting stents (DES)
      in multiple randomized trials. Several single-center non-randomized registries
      have evaluated the role of DES for LM-PCI. Data suggest a low mortality and
      target vessel failure of ostial LM or mid-shaft lesions in contrast to
      bifurcation lesions, which frequently require complex dual stenting techniques.
      The complex PCI in the bifurcation is associated with the increased occurrence of
      target vessel failure ranging from 2% and 38%. The rate of target vessel failure
      in bifurcation lesions is less in patients in whom the circumflex ostium is not
      involved so that single cross over stent is suitable. Current recommendations
      call for a follow-up angiography at 4-6 months to detect LM restenosis prior to a
      potentially fatal clinical event. The question of the duration of dual
      antiplatelet therapy in patients who underwent LM-PCI is unanswered. More
      registry data and randomized trials are needed before unprotected LM-PCI can be
      routinely offered to patients as an alternative to CABG.

PMID- 17019400
TI  - PCI versus CABG versus medical therapy in 2006.
AB  - The decision to offer patients with myocardial ischemia a coronary artery bypass
      graft (CABG) surgery has been largely determined by extent of coronary artery
      disease (CAD) and left ventricular function, since the early 1970's. Based upon
      subset analyses, and long-term follow-up, of three moderate-sized trials of
      stable patients and two small trials of unstable angina (excluding recent
      myocardial infarction, MI) patients, the notion has persisted that patients with
      left main narrowing >50% or three-vessel stenoses >70%, or even two-vessel
      stenoses >70%, where one of the vessels is the proximal left anterior descending,
      derive a "survival benefit" relative to medical therapy (MED), from CABG
      (anatomic paradigm). The MED of the original CABG versus MED trials consisted of
      little more than anti-anginal medications, used on an as-needed basis. In the
      ensuing 3 decades, multiple large, well done, randomized clinical trials have
      established a survival benefit for 4 different forms of MED among a broad
      spectrum of CAD patients. Aspirin; lipid lowering, especially with statins; b
      blockers; and angiotensin-converting-enzyme inhibitors and/or angiotensin
      receptor blocking agents; have all been shown to enhance survival, as well as
      reduce other objective adverse outcomes of CAD. The advances in MED, coupled with
      the small but significant mortality and morbidities of both CABG and percutaneous
      coronary intervention (PCI), are among the reasons to skeptically consider
      potential "survival benefit" of revascularization. A more common and far more
      easily justified reason to consider revascularization is to relieve "medically
      refractory" myocardial ischemia, particularly when the ischemia is accompanied by
      symptoms. Accordingly, documentation of medically refractory myocardial ischemia
      provides the answer to the first question of myocardial revascularization, "Is
      this patient likely to derive clinical benefit from revascularization, at this
      time?" It is only after this question has been answered that one needs to
      consider the relative advantages and disadvantages of PCI versus CABG
      (physiologic paradigm). Two of the relative advantages of PCI, namely speed of
      reperfusion, and relatively low morbidity, are among the reasons that most
      randomized trial data, and most clinical application of revascularization to
      patients with MI (ST-elevation MI [STEMI], and non-STEMI) have been by PCI. In
      contrast, for stable patients with medically refractory ischemia, anatomic
      considerations continue to be relevant to the choice between CABG and PCI.
      Specific advantages of CABG include: its potential to revascularize chronically
      occluded vessels with collaterals supplying viable myocardium; the fact that
      conduits protect territories rather than simply treating lesions; and the greater
      durability of conduits compared to bare-metal stents (drug-eluting stents may
      change the picture). Based on these principles, physiologic, rather than
      anatomic, considerations are most useful in determining whether to revascularize,
      and how urgently to revascularize (STEMI is an emergent indication and high-risk
      non-STEMI an urgent indication). Coronary anatomy, including both number of
      vessels and lesion characteristics, continues to help decide between CABG and
      PCI, and in formulating patient specific strategies.

PMID- 17019401
TI  - Carotid artery stenting: where are we now?
AB  - Carotid artery disease is a frequent risk factor for ischemic stroke. Carotid
      endarterectomy was considered to be the standard treatment for high graded
      stenosis until carotid artery stenting (CAS) developed with promising results in
      early series and randomized trials. At present, stenting is supported in patients
      at high risk for surgery. Randomized trials analyzing low risk patient groups and
      studying the long-term results of CAS are necessary and partly underway. Although
      randomized trials are not yet available, current evidence suggests that cerebral
      protection devices reduce the number of neurological events. This review
      discusses the results of randomized trials and clinical series.

PMID- 17019402
TI  - Interventional therapy for carotid artery disease using angioplasty and stenting
      with embolic protection.
AB  - Carotid artery angioplasty with stenting (CAS) has emerged as a viable
      alternative to endarterectomy for the treatment of occlusive vascular disease.
      Advances in endovascular techniques and the improvement of specialized stents
      have served to rapidly close the gap with the traditional gold standard surgery.
      Furthermore, the development of cerebral embolic protection devices has reduced
      the occurrence of distal embolization of atheromatous material during such
      interventions and has reduced periprocedural stroke rates considerably. Continued
      improvements in distal embolic protection have further improved the risk profile
      of CAS, and increased operator experience with these interventional procedures
      has also been shown to reduce periprocedural complication rates. Outcomes may
      continue to improve as more providers gain experience with the evolving
      endovascular device technology, and several prospective clinical trials are
      currently investigating the efficacy of CAS with embolization protection versus
      endarterectomy in different cohorts. This review will survey the background and
      current literature covering angioplasty and stenting for occlusive disease in the
      carotid arteries and discuss the current methods employed to prevent distal
      emboli during intervention.

PMID- 17019403
TI  - Contemporary antithrombotic treatment after coronary stenting in patients with
      indication for long-term anticoagulation.
AB  - AIM: Dual antiplatelet treatment with aspirin and a thienopyridine is the
      antithrombotic treatment recommended after percutaneous coronary intervention
      with stent implantation (PCI-S). Optimal treatment in patients with an indication
      for long-term oral anticoagulation (OAC) undergoing PCI-S is currently undefined.
      The aim of this study was to evaluate the contemporary management of these
      patients, and determine the safety and the efficacy of the various regimens.
      METHODS: A systematic review of the literature reporting on this issue was
      carried out. RESULTS: The adopted strategies showed substantial variability, and
      the regimens used included: substitution of OAC for dual antiplatelet therapy in
      25-54% of cases, addition to OAC of a single antiplatelet agent in 12-25% and
      institution of triple therapy with OAC (or low-molecular-weight heparin), aspirin
      and a thienopyridine in about 60%. OAC was systematically aimed at a lower
      intensity in 33% of cases, whereas in another 29% this was pursued only when a
      high hemorrhagic risk was perceived. Both safety and efficacy of the various
      regimens appeared suboptimal, with a 30-day occurrence of major bleeding and
      thrombotic complications of 3-7% and 4%, respectively. CONCLUSIONS: Due to the
      suboptimal safety and/or efficacy of the various regimens adopted, the optimal
      antithrombotic treatment in patients with an indication for OAC undergoing PCI-S
      remains to be defined. Since the number of this patient subgroup is foreseen to
      progressively increase over the next years, large scale registries and clinical
      trials are warranted.

PMID- 17019405
TI  - Peroxisome proliferator-activated receptor gamma activation relieves expression
      of behavioral sensitization to methamphetamine in mice.
AB  - Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated
      transcriptional factor that regulates lipid metabolism and inflammation.
      Behavioral sensitization is an experimental model of psychostimulant psychosis;
      it is elicited by repeated administration of psychostimulants and has recently
      been implicated in brain inflammation. We examined the involvement of PPARgamma,
      one of the isotypes of PPAR, in development of behavioral sensitization to the
      stimulant effect of methamphetamine (METH) (1 mg/kg, subcutaneously) in mice.
      Repeated administration of METH (once daily for 5 days) enhanced the locomotor
      activating effect of METH, which was reproduced by METH challenge on withdrawal
      day 7 (test day 12). The protein level and the activity of PPARgamma were
      significantly increased in the nuclear fraction of whole brain after 5 days of
      METH administration (test day 5) and on withdrawal day 7 (test day 12). Both
      pioglitazone and ciglitazone (PPARgamma agonists; 0.5-5.0 microg,
      intracerebroventricularly (i.c.v.), once daily) prevented the expression of
      behavioral sensitization to METH challenge on withdrawal day 7, but not the
      sensitization that occurred during repeated administration of METH. In addition,
      the magnitude of expression of behavioral sensitization was augmented by
      treatments with GW9662 (a PPARgamma antagonist; 0.5-5.0 microg i.c.v., once
      daily) during the withdrawal period. The pioglitazone-induced alleviation of
      behavioral sensitization was synergistically facilitated by simultaneous i.c.v.
      injection of 9-cis-retinoic acid (1.0 microg), an agonist for the retinoid X
      receptor which is a ligand-activated nuclear receptor that forms heterodimers
      with PPAR. These results suggest that PPARgamma has a significant role in the
      expression of behavioral sensitization to METH in mice.

PMID- 17019406
TI  - Effects of acute tryptophan depletion on mood and facial emotion perception
      related brain activation and performance in healthy women with and without a
      family history of depression.
AB  - The present study examined the effects of acute tryptophan (Trp) depletion (ATD),
      a well-recognized method to lower central serotonin (5-HT) metabolism, on brain
      activation during a facial emotion perception task. Brain activation was measured
      using fMRI, and healthy female volunteers with a positive family history of
      unipolar depression (FH+) were compared to healthy female volunteers without such
      a history (FH-). Participants viewed two morphed faces and were instructed to
      choose between the faces based either on the intensity of the emotional
      expression (direct task) or the gender of the face (incidental task). In the FH+
      group, depletion led to the expected lowering of mood, which partly determined
      the effect of depletion on performance and brain activation. A stronger mood
      lowering effect was associated with less accurate performance on faces expressing
      a negative emotion in the incidental task and a stronger right amygdala response
      to fearful faces in comparison to happy faces. These results were explained in
      terms of a mood-induced bias leading to a stronger impact of the expressed
      negative emotion which subsequently leads to more interference in the incidental
      task and a stronger amygdala response. It was concluded that the effects of ATD
      on mood, performance, and brain activation in a facial emotion perception task
      depend on family history of depression. Performance and brain activation partly
      depend on the effect of ATD on mood.

PMID- 17019404
TI  - Delayed satiety-like actions and altered feeding microstructure by a selective
      type 2 corticotropin-releasing factor agonist in rats: intra-hypothalamic
      urocortin 3 administration reduces food intake by prolonging the post-meal
      interval.
AB  - Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized
      to control feeding, with central administration of 'type 2' urocortins producing
      delayed anorexia. The present study sought to identify the receptor subtype,
      brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal
      food intake in rats. Non-food-deprived male Wistar rats (n=176) were administered
      Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or
      paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala
      (MeA), regions in which Ucn 3 is expressed in proximity to CRF(2) receptors. LV
      Ucn 3 suppressed ingestion during the third-fourth post-injection hours. LV Ucn 3
      anorexia was reversed by cotreatment with astressin(2)-B, a selective CRF(2)
      antagonist and not observed following equimole subcutaneous or fourth ventricle
      administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV
      infusion, reduced the quantity (57-73%) and duration of ingestion (32-68%) during
      the third-fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn
      3 slowed the eating rate and reduced intake by prolonging the post-meal interval.
      Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the
      regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally
      specific, because minimal effective anorectic Ucn 3 doses did not alter drinking
      rate or promote a conditioned taste aversion, and site-specific, because intra
      MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering
      total intake. The results implicate the VMN and PVN of the hypothalamus as sites
      for Ucn 3-CRF(2) control of food intake.

PMID- 17019407
TI  - Accumbal neurons that are activated during cocaine self-administration are spared
      from inhibitory effects of repeated cocaine self-administration.
AB  - Hypoactivity of the accumbens is induced by repeated cocaine exposure and is
      hypothesized to play a role in cocaine addiction. However, it is difficult to
      understand how a general hypoactivity of the accumbens, which facilitates
      multiple types of motivated behaviors, could contribute to the selective increase
      in drug-directed behavior that defines addiction. Electrophysiological
      recordings, made during sessions in which rats self-administer cocaine, show that
      most accumbal neurons that encode events related to drug-directed behavior
      achieve and maintain higher firing rates during the period of cocaine exposure
      (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated
      neurons). We have hypothesized that this difference in activity makes the neurons
      that facilitate drug-directed behavior less susceptible than other neurons to the
      chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug
      directed behavior from chronic hypoactivity might lead to a relative increase in
      the transmission of neuronal signals that facilitate drug-directed behavior
      through accumbal circuits and thereby contribute to changes in behavior that
      characterize addiction (ie differential inhibition hypothesis). A prediction of
      the hypothesis is that neurons that are activated in relation to task events
      during cocaine self-administration sessions will show less of a decrease in
      firing across repeated self-administration sessions than will other neurons. To
      test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self
      administration sessions. Chronic extracellular recordings of single accumbal
      neurons were made during the second to third session and the 30th session.
      Between-session comparisons showed that decreases in firing were exhibited by
      Task-Non-Activated, but not by Task-Activated, neurons. During the day 30
      session, the magnitude of the difference in firing rate between the two groups of
      neurons was positively related to the propensity of animals to seek and take
      cocaine. The findings of the present study are consistent with a basic prediction
      of the differential inhibition hypothesis and may be relevant to understanding
      cocaine addiction.

PMID- 17019408
TI  - Fluvoxamine treatment and D2 receptors: a pet study on OCD drug-naive patients.
AB  - Changes in D(2) receptors during antidepressant therapy have been reported in
      patients with major depressive disorder using PET/SPET. The aim of this study was
      to evaluate modifications in D(2) receptors that might occur in patients affected
      by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors
      (SSRIs). To this purpose, we measured the in vivo binding of [(11)C]raclopride
      ([(11)C]Rac)in the brain of a group of OCD naive patients before and after the
      repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a
      Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of
      OCD completed the study undergoing a PET scan and a complete clinical evaluation
      before and during treatment with fluvoxamine. Patients have been compared also
      with a group of nine age-matched normal volunteers. Fluvoxamine treatment
      significantly improved clinical symptoms and increased [(11)C]Rac binding
      potential (BP) in the basal ganglia of OCD patients (7.5+/-5.2, 6.9+/-6.9, and
      9.9+/-9.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia,
      respectively; p<0.01) to values closer to those observed in the group of normal
      subjects. Chronic treatment with fluvoxamine induces a slight but significant
      increase in striatal [(11)C]Rac BP of previously drug-naive OCD patients. The
      modifications in D(2) receptor availability might be secondary to fluvoxamine
      effects on serotoninergic activity.

PMID- 17019409
TI  - SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1)
      binding and functional profile.
AB  - In this paper, we report on the pharmacological and functional profile of
      SSR180711 (1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester),
      a new selective alpha7 acetylcholine nicotinic receptor (n-AChRs) partial
      agonist. SSR180711 displays high affinity for rat and human alpha7 n-AChRs (K(i)
      of 22+/-4 and 14+/-1 nM, respectively). Ex vivo (3)[H]alpha-bungarotoxin binding
      experiments demonstrate that SSR180711 rapidly penetrates into the brain
      (ID(50)=8 mg/kg p.o.). In functional studies performed with human alpha7 n-AChRs
      expressed in Xenopus oocytes or GH4C1 cells, the compound shows partial agonist
      effects (intrinsic activity=51 and 36%, EC(50)=4.4 and 0.9 microM, respectively).
      In rat cultured hippocampal neurons, SSR180711 induced large GABA-mediated
      inhibitory postsynaptic currents and small alpha-bungarotoxin sensitive currents
      through the activation of presynaptic and somato-dendritic alpha7 n-AChRs,
      respectively. In mouse hippocampal slices, the compound increased the amplitude
      of both glutamatergic (EPSCs) and GABAergic (IPSCs) postsynaptic currents evoked
      in CA1 pyramidal cells. In rat and mouse hippocampal slices, a concentration of
      0.3 muM of SSR180711 increased long-term potentiation (LTP) in the CA1 field.
      Null mutation of the alpha7 n-AChR gene totally abolished SSR180711-induced
      modulation of EPSCs, IPSCs and LTP in mice. Intravenous administration of
      SSR180711 strongly increased the firing rate of single ventral pallidum neurons,
      extracellularly recorded in anesthetized rats. In microdialysis experiments,
      administration of the compound (3-10 mg/kg i.p.) dose-dependently increased
      extracellular acetylcholine (ACh) levels in the hippocampus and prefrontal cortex
      of freely moving rats. Together, these results demonstrate that SSR180711 is a
      selective and partial agonist at human, rat and mouse alpha7 n-AChRs, increasing
      glutamatergic neurotransmission, ACh release and LTP in the hippocampus.

PMID- 17019410
TI  - Update on orbital anatomy.
AB  - The orbit is a confined space bounded by four bony walls. Apart from the globe,
      orbital fat, and extraocular muscles it contains many important neurovascular
      structures. It is intimately related to the paranasal sinuses as well as the
      anterior and middle cranial fossae. Consequently, sinus pathology and
      intracranial disease may spread to involve the orbit and the converse applies. A
      thorough understanding of orbital anatomy is essential to fully appreciate the
      effects of disease on the orbit and is of paramount importance for performing
      safe orbital surgery. The anatomy of the orbit is discussed with reference to
      relevant orbital disease.

PMID- 17019411
TI  - Orbital vascular anatomy.
AB  - The anatomy of the orbital vascular bed is highly complex, with tremendous
      interindividual variations. The main source of blood supply to the orbit is by
      the ophthalmic artery, the first branch of the internal carotid artery. The
      origin, course, and branches of the ophthalmic artery, and the genesis of the
      variations in origin, course, and branching pattern of the ophthalmic artery are
      discussed. The external carotid artery normally contributes only to a small
      extent to the orbital blood supply via the infraorbital artery and orbital branch
      of the middle meningeal artery.The complex, highly variable and confusing orbital
      venous system can be divided into: (i) main orbital veins (superior and inferior
      ophthalmic veins), (ii) inconstant orbital veins (middle and medial ophthalmic
      veins and four collateral veins), (iii) orbital venous networks, and (iv) various
      venous tributaries. All these are described briefly.

PMID- 17019412
TI  - Orbital lymphatics: do they exist?
AB  - INTRODUCTION: Although the lymphatic system was first described almost 400 years
      ago, it is only in very recent years that researchers have been able to identify
      lymphatic channels with reasonable accuracy. Through advances in molecular
      biology and the development of endothelial cell markers the long held view that
      the human orbit is devoid of lymphatics has now been challenged. DISCUSSION: This
      review discusses the current evidence on this topic, which confirms the presence
      of orbital lymphatics in lachrymal gland and optic nerve sheath.

PMID- 17019413
TI  - Optic glioma warranting treatment in children.
AB  - PURPOSE: To describe cases of optic pathway glioma (OPG) warranting treatment in
      children. METHODS: This is a retrospective review of pediatric patients treated
      for OPG. The clinical data and imaging studies were obtained from the medical
      records and radiology files of patients seen at the Pediatric Neuro-Ophthalmology
      Clinic at the University of Illinois, Chicago and the private office of the
      author (LMK). RESULTS: A total of seven cases with an age range of 3-48 months at
      presentation were reviewed. Three of the patients were also ultimately diagnosed
      with neurofibromatosis type 1. Presenting symptoms included proptosis, decreased
      vision, gaze deficit, and nystagmus. Four patients underwent biopsies that
      confirmed OPG. Six of the patients were treated with intravenous chemotherapy,
      with three patients requiring a second chemotherapy cycle. One patient was
      successfully treated with an en-bloc optic nerve excision. Two patients underwent
      unilateral enucleation owing to globe complications. CONCLUSION: Although benign
      tumours, OPG can behave very aggressively in young children. Both chemotherapy
      and en-bloc excision can be employed for treatment.

PMID- 17019414
TI  - Orbital exenteration for invasive skin tumours.
AB  - Orbital exenteration aims at local control of disease invading the orbit that is
      potentially fatal or relentlessly progressive. Of all exenterations presenting to
      ophthalmologists, 40-50% are required for tumours in the eyelid or periocular
      skin. 99% of these are basal cell carcinomas and 4-6% each are squamous cell
      carcinomas or sebaceous gland carcinomas. Orbital invasion results in progressive
      fixation of the tumour to bone and reduced ocular motility. Perineural invasion
      of branches of the trigeminal nerve leads to numbness or pain, and that the
      facial nerve, to weakness. Biopsy identifies the cell type and the presence of
      perineural invasion. CT and MRI scanning help in the assessment of tumour spread
      within the orbit. Management should be in collaboration with an oncologist.
      Exenteration may be total-the removal of all orbital contents-or lid-sparing if
      the tumour is placed posteriorly. The socket may be allowed to heal by
      granulation or lined with a split skin graft or local flap. Complications may be
      seen following 20-25% of exenterations and include fistulae, tissue necrosis,
      exposed bone, and infection. Incomplete clearance of tumours occurs in about 38%
      of total exenterations and 17% of subtotal. The overall 5-year survival is 55
      65%, but significantly worse if there was perineural spread. Facial prostheses
      may be mounted on glasses or secured with tissue glue or osseointegrated
      implants. Excellent cosmetic results can be achieved but many patients prefer to
      wear a patch.

PMID- 17019415
TI  - Avoiding surgery for thyroid eye disease.
AB  - In thyroid eye disease, autoimmune inflammation of orbital musculature and fat
      increases the bulk of the orbital contents. Orbital tension rises and patients
      stratify according to the ease with which their globes can proptose. Restriction
      of proptosis is associated with optic nerve compression and visual loss;
      exophthalmos, with corneal damage. Ocular motility is affected, initially by
      muscle inflammation; late in the disease, by fibrosis. Extraocular factors,
      including thyroid endocrine disturbance, antigen release, infections,
      malignancies, and smoking, may trigger and drive the orbital myopathy. The
      management of thyroid eye disease by the identification and treatment of drives,
      followed by immunomodulatory therapy, is discussed. Fourteen patients with
      compressive optic neuropathy were treated with immunomodulation using intravenous
      methylprednisolone, oral prednisolone, and cyclosporin A, and followed up for a
      minimum of three years. All recovered their pre-morbid visual acuities and visual
      fields in both eyes. Severe disturbances of ocular motility also recovered in 30
      patients, treated with the same regime. In one subject, ocular motility
      normalised with intravenous steroids and cyclosporin A, but no oral prednisolone.
      Morbidity from the treatment was low. Immunomodulation is a rational and
      successful method for managing optic nerve compression and disordered motility in
      this condition.

PMID- 17019416
TI  - Postural visual obscurations in patients with inactive thyroid eye disease; a
      variant of 'hydraulic' disease.
AB  - AIM: This investigation newly describes the characteristics and treatment for a
      group of patients with inactive thyroid eye disease who presented with recurrent
      transient visual obscuration, generally related to sudden changes in posture.
      STUDY DESIGN: A retrospective case-note review of an unmatched case series.
      PATIENTS AND METHODS: Clinical records were reviewed for patients with thyroid
      eye disease, presenting to the Orbital Clinic at Moorfields Eye Hospital with
      recurrent transient visual obscuration. All patients underwent orbital
      decompression and the response to this, and other, treatment was reviewed.
      RESULTS: Six patients (five female) presented to the Orbital Clinic, between the
      ages of 43 and 66 years (mean 54.7; median 52 years), with recurrent visual
      obscurations related to postural changes. Transient obscurations had been noted
      for between 3 weeks and 2 months, the patients having had symptoms of underlying
      thyroid eye disease for between 6 and 18 months. Five patients had diabetes for
      between 2 and 45 years, four being controlled with insulin and one with
      metformin. All patients had increased orbital tension on clinical assessment,
      intraocular pressures were raised in 5/6, and the optic disc in affected eyes was
      markedly swollen (with bilateral choroidal folds in two patients). Hertel
      exophthalmometry ranged from 22 to 27 mm, and there was a global reduction in
      ocular ductions in all. Bilateral orbital decompression was performed in all
      patients, although sequentially in one patient: 4/6 patients had three-wall
      decompression with an average proptosis reduction of 5.8 mm (range 2-8 mm; eight
      orbits) and 2/6 had decompression of the medial wall and floor alone (mean
      reduction 6.8 mm, range 5-8 mm; four orbits). In all patients, there was an
      almost immediate cessation of obscurations, together with a subjective and
      objective improvement in various visual functions. Optic disc swelling resolved
      over a few weeks after surgery. CONCLUSION: The 'hydraulic' variant of thyroid
      eye disease-characterised by high orbital apex pressures, with secondarily raised
      episcleral venous and intraocular pressures-may be linked with certain orbital
      shapes, such as that of Asians. This variant can present with recurrent visual
      obscuration associated with transient postural hypotension, especially in
      diabetics-this possibly being due to a microvasculopathy of the orbital or optic
      nerve circulation.

PMID- 17019417
TI  - Monoclonal antibodies in the diagnosis of lymphoproliferative diseases of the
      orbit and orbital adnexae.
AB  - AIMS: To describe the value of monoclonal antibodies in the differential
      diagnosis of orbital lymphoproliferative disorders. METHODS: A total of 200
      sequential cases of malignant lymphoma diagnosed at St Bartholomew's Hospital as
      part of the ocular lymphoma service at Moorfields Eye Hospital and the Institute
      of Ophthalmology have been examined. Cases were acquired between January 1998 and
      June 2005. Each case had detailed immunophenotypic analysis using a panel of
      monoclonal antibodies and was classified using the WHO classification of
      lymphoma. These cases are discussed in relation to earlier studies of orbital
      lymphoma reported by our group. RESULTS: Lymphomas fell into three main
      categories. Extranodal marginal zone lymphoma was the largest group with 151
      cases, arising within the orbital soft tissue, conjunctiva and lacrimal gland.
      Cases arising in the conjunctiva and lacrimal gland showed a higher female
      predominance than those arising within the deeper soft tissue. A small number of
      cases were associated with organ specific autoimmunity, including thyroid eye
      disease complicating Graves' disease. Follicular lymphoma and diffuse large B
      cell lymphoma formed the next two groups, occurring with equal frequency. Many of
      the follicular lymphomas had evidence of disseminated disease on completion of
      staging. A miscellaneous group of T-cell and B-cell lymphomas formed a minority
      of cases during the study period. CONCLUSION: Extranodal marginal zone lymphoma
      is the most frequent type of primary orbital and orbital adnexal lymphoma. Its
      major differential diagnosis is with orbital lymphoid hyperplasia, chronic
      dacryoadenitis, and follicular conjunctivitis. Systemic types of lymphoma may
      present within the orbit or involve the orbit secondarily.

PMID- 17019418
TI  - Imaging features of ocular adnexal lymphoproliferative disease.
AB  - PURPOSE: To evaluate the imaging characteristics of a cohort of patients with
      ocular adnexal lymphoproliferative disease (OALD). METHODS: A noncomparative
      retrospective review between 1992 and 1995 and prospective study from 1995 to
      2005 of the clinical, imaging and treatment of 105 patients presenting to
      tertiary orbital referral centre presenting with OALD. RESULTS: One hundred and
      five patients (mean age 61 years, range 11-90 years) with equal gender
      distribution were included. Fifty-three were primary and 52 were secondary.
      Computed tomography (CT) usually showed a well-circumscribed lesion of greater
      than brain density, moulding to adjacent tissues with moderate enhancement.
      Aggressive histology was associated with bone destruction, while moulding was
      associated with indolent histology (P<0.005).MRI in OALD showed intermediate
      signal intensity on T1- and T2-weighted images and moderate enhancement with
      gadolinium. Gallium scanning sensitivity to detect ocular adnexal disease was 25
      and 57% for systemic involvement. Positron emission tomography (PET) upstaged
      (71%) of patients with systemic lymphoproliferative involvement, having a higher
      sensitivity than CT in detecting distant disease (86 vs 72%). CONCLUSIONS: CT
      and/or MRI are essential in the evaluation of OALD and can be used to establish
      that an orbital lesion may be lymphoprolifetaive in nature. Further, these
      imaging modalities may predict the behaviour of the lymphoma in certain cases.
      Gallium scanning provides no additional information to CT and does not influence
      patient treatment. PET represents an important addition to the assessment of OALD
      with real impact on patient management.

PMID- 17019419
TI  - Orbital inflammatory disease: a diagnostic and therapeutic challenge.
AB  - The spectrum of orbital inflammatory disease (OID) ranges broadly from specific
      disease diagnoses, for example, Wegener's granulomatosis or sarcoidosis, to
      nonspecific inflammation which may involve one or multiple structures of the
      orbit. Mimics of idiopathic OID must be considered in a comprehensive
      differential diagnosis and include malignancies, congenital mass lesions,
      infectious diseases, and occult or distant trauma. Idiopathic OID may be
      secondary to an underlying systemic inflammatory disease, which must be diagnosed
      in order to develop a comprehensive therapeutic plan, or may represent localized
      pathologic processes without systemic involvement. Evaluation of the patient with
      suspected OID must include a careful history, physical examination, directed
      laboratory, and radiologic studies, and may sometimes require tissue for
      diagnostic studies. Therapeutic options for inflammatory diseases are expanding
      as biologically targeted agents become available that act on specific segments of
      the inflammatory cascades. The purpose of this paper is to provide a framework
      for the evaluation and management of patients with the spectrum of diseases known
      as OID and to discuss some of the new advances in immunologic monitoring and
      targeted immune therapies that will likely play an increasingly important role in
      the care of these patients.

PMID- 17019420
TI  - Orbital blow-out fractures: surgical timing and technique.
AB  - PURPOSE: To recommend a tailored approach to surgical timing in the repair of
      orbital blow-out fractures, and to offer suggestions for improved functional and
      aesthetic surgical outcomes. METHODS: Traditional guidelines for surgical timing
      are reviewed. An evidence-based approach that considers soft-tissue disruption
      relative to bone-fragment separation is presented. The author's techniques for
      repair of isolated orbital floor, isolated medial wall, and combined floor-medial
      wall fractures are presented. RESULTS: As demonstrated previously, greater
      degrees of soft-tissue incarceration or displacement, with presumably greater
      intrinsic damage and subsequent fibrosis, result in poorer motility outcomes
      despite complete release of soft tissues. There is a suggestion that earlier
      intervention for such injuries might improve outcomes. Lower fornix and
      transcaruncular incisions, careful extrication of incarcerated tissue, and thin
      alloplastic implants have proven successful in the author's hands. CONCLUSIONS:
      The degree of soft-tissue displacement relative to bone fragment distraction, as
      depicted in preoperative computed tomography (CT) scans, should be considered in
      the timing of surgery. Incisions, soft-tissue handling, and implant material,
      thickness, and positioning can all affect the functional and aesthetic outcomes.

PMID- 17019421
TI  - Endoscopic transnasal orbital decompression for visual failure due to sphenoid
      wing meningioma.
AB  - AIM: To review a group of patients with sphenoid wing meningioma and visual
      impairment. The technique and results for endoscopic transnasal decompression of
      the orbital apex is presented. PATIENTS AND METHODS: Patients presenting between
      1993 and 2004 with visual impairment due to sphenoid wing meningioma were
      identified. All patients had full ophthalmic assessment, automated visual field
      testing, and appropriate orbital imaging. Patients with clinical evidence of
      significant progression in visual impairment (loss of acuity, reduced colour
      discrimination, or field deterioration) underwent endoscopic transnasal orbital
      decompression. OUTCOME MEASURES: Assessment of visual function (Snellen acuity,
      Ishihara colour perception, and visual field testing), together with other
      measures of orbital structure and function (ocular balance, ductions, and
      exophthalmometry). RESULTS: Twelve patients (all women) presented to the Orbital
      Clinic between the ages of 38 and 71 years (mean 42.6; median 48.5 years) and
      with symptoms for an average of 32 months (3-102 months; median 22). The most
      common symptom was swelling and proptosis, in 11 (91%) patients, and subjective
      deterioration of vision had been noted in six cases (50%). Eight right orbits
      (67%) were affected and the preoperative acuity varied between Snellen 6/5 and
      counting fingers, with visual field impairment in all cases. There was an average
      of 5.0 mm of axial proptosis (range 5-9 mm; median 5). Endoscopic decompression
      was without complication in all cases. With a follow-up interval of 33.9 months
      (range 5-80; median 26 months), there was a subjective and objective improvement
      in visual functions-with Snellen acuity improving between 1 and 4 lines in seven
      patients, reduction in relative afferent pupillary defect in 10/12 patients, and
      improved visual field testing. There was a 2.3 mm reduction in proptosis (1-4 mm;
      median 3 mm) with less lid swelling, improved ocular balance and motility in four
      patients, and slightly worse diplopia in one patient. Three patients required
      further procedures: one had ipsilateral middle meatal antrostomy for retained
      secretions at 18 months and two had strabismus surgery. Three patients underwent
      fractionated radiotherapy for large tumours, or for late tumour growth and
      recurrent visual impairment. CONCLUSION: Orbital decompression by transnasal
      endoscopic ethmoidectomy appears to alleviate optic nerve compression due to
      sphenoid wing meningioma, with a reasonable relief of the condition for some
      years. Some patients will require later radiotherapy for progressive tumour
      growth or visual failure.

PMID- 17019422
TI  - Cosmetic orbital surgery.
AB  - PURPOSE: Current indications for orbital surgery primarily aimed at improving
      cosmesis are considered in the context of subspecialist orbital practice by an
      ophthalmologist. SCOPE: Thyroid eye disease, orbital vascular anomalies, and
      dermolipomas are common orbital diseases in which the symptoms can be purely
      cosmetic. Accurate anatomical awareness, preoperative scanning, control of
      medical factors including smoking and thyroid status, and endoscopic techniques
      have all contributed to the aesthetic outcome of orbital surgery. The threshold
      for performing reconstructive orbital surgery has also been lowered by public
      demand. CONCLUSIONS: Orbital surgeons can therefore offer the familiar
      techniques, such as orbital decompression, for pure cosmesis. Sensitive history
      taking and awareness of the psychological element are of paramount importance for
      the orbital surgeon who develops a cosmetic practice.

PMID- 17019423
TI  - Craniofacial surgery for orbital malformations.
AB  - Paediatric craniofacial surgery is a highly specialised field requiring a
      multidisciplinary team input. Orbital and ocular involvement is relatively common
      in craniofacial patients. This is more in syndromic patients. In nonsyndromic
      patients, orbital involvement is common in frontal plagiocephaly and
      trigonocephaly. The management of these conditions requires close working between
      the craniofacial surgeon and ophthalmologist. An outline of the management of
      these deformities is discussed.

PMID- 17019424
TI  - Natural history of periocular capillary haemangiomas: changes in internal blood
      velocity and lesion volume.
AB  - AIM: Although the clinical characteristics of childhood periocular capillary
      haemangiomas are well known, serial measurements of blood velocity and lesion
      size are unknown. This investigation was designed to measure the changes in
      maximum blood velocity and estimated size of lesion in children with capillary
      haemangioma not requiring active intervention. STUDY DESIGN: Retrospective case
      note review for a cohort of children with capillary haemangioma involving the
      eyelid and orbit. PATIENTS AND METHODS: Children with periocular capillary
      haemangioma, under the care of the Orbital unit at Moorfields Eye Hospital
      between 1996 and 2005, were monitored clinically and with repeated
      ultrasonographic examination. Volume estimates were calculated as an ovoid based
      on the three maximum orthogonal measurements for the haemangioma, and blood
      velocity was assessed by Colour Flow Mapping, Colour Doppler Energy Imaging, and
      Spectral Doppler techniques using a Sequoia 512 Acuson scanner. RESULTS: Twenty
      four children (12 boys) had initial assessment by 18 months of age, and the
      haemangioma increased in size in 14/24 (58%), the increase being between 4 and
      931% of initial volume estimate. The largest measured size for an individual
      haemangioma appears inversely related to the child's age at measurement, this
      mirroring a similar trend in measurements for the maximum blood velocity. Blood
      velocity measurements also tend to decrease with time, the peak velocity being
      before 1 year of age in the majority (15/24; 62%). In many children, both volume
      estimates and blood velocities show a cyclic variation-this occurring with
      increasing intervals between the maxima, before a final decay in both parameters.
      Although, for the whole group, there was no correlation (correlation
      coefficient=0.29) between estimated size and measured blood velocity, some
      individual children showed a significant correlation between the two parameters.
      The age at maximum blood velocity appeared to precede the age at maximum volume
      in most children, and in many there was an orbital anomaly detectable on
      ultrasonographic examination, even with complete clinical resolution of the
      haemangioma. CONCLUSIONS: Ultrasonographic examination of periocular capillary
      haemangiomas show that these lesions have a very high blood velocity in feeding
      vessels-about 2-3 orders of magnitude greater than normal capillary beds-and that
      the velocity and volume of such lesions undergo a cyclic variation during their
      natural history. Evidence suggests that both velocity and volume decrease with
      time, although often not returning to zero on ultrasonography (unlike the
      clinical resolution of the lesions). In most children, blood velocity peaks
      before volume estimates and this might suggest that decreasing perfusion leads to
      later tissue atrophy and involution of the haemangioma.

PMID- 17019426
TI  - The dilemma and promise of cancer chemoprevention.

PMID- 17019427
TI  - The conundrum of fluoroquinolone prophylaxis.

PMID- 17019428
TI  - Can ovarian function be protected in young women receiving chemotherapy?

PMID- 17019429
TI  - Can prostate-specific antigen nadir predict prostate cancer outcomes following
      radiotherapy?

PMID- 17019430
TI  - Paclitaxel and carboplatin versus mitoxantrone: lessons of an underpowered study.

PMID- 17019431
TI  - Gene expression profiling for individualized breast cancer chemotherapy: success
      or not?

PMID- 17019432
TI  - Gene signature evaluation as a prognostic tool: challenges in the design of the
      MINDACT trial.
AB  - This Review describes the work conducted by the TRANSBIG consortium in the
      development of the MINDACT (Microarray In Node negative Disease may Avoid
      ChemoTherapy) trial. The goal of the trial is to provide definitive evidence
      regarding the clinical relevance of the 70-gene prognosis signature, and to
      assess the performance of this signature compared with that of traditional
      prognostic indicators for assigning adjuvant chemotherapy to patients with node
      negative breast cancer. We outline the background work and the key questions in
      node-negative early-stage breast cancer, and then focus on the MINDACT trial
      design and statistical considerations. The challenges inherent in this trial in
      terms of logistics, implementation and interpretation of the results are also
      discussed. We hope that this article will trigger further discussion about the
      difficulties of setting up and analyzing trials aimed at establishing the worth
      of new methods for better selection of patients for cancer treatment.

PMID- 17019433
TI  - Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn
      for an old therapy.
AB  - Oral estrogens were the treatment of choice for carcinoma of the prostate for
      over four decades, but were abandoned because of an excess of cardiovascular and
      thromboembolic toxicity. It is now recognized that most of this toxicity is
      related to the first pass portal circulation, which upregulates the hepatic
      metabolism of hormones, lipids and coagulation proteins. Most of this toxicity
      can be avoided by parenteral (intramuscular or transdermal) estrogen
      administration, which avoids hepatic enzyme induction. It also seems that a short
      term but modest increase in cardiovascular morbidity (but not mortality) is
      compensated for by a long-term cardioprotective benefit, which accrues
      progressively as vascular remodeling develops over time. Parenteral estrogen
      therapy has the advantage of giving protection against the effects of andropause
      (similar to the female menopause), which are induced by conventional androgen
      suppression and include osteoporotic fracture, hot flashes, asthenia and
      cognitive dysfunction. In addition, parenteral estrogen therapy is significantly
      cheaper than contemporary endocrine therapy, with substantive economic
      implications for health providers.

PMID- 17019434
TI  - Mechanisms of Disease: cancer targeting and the impact of oncogenic RET for
      medullary thyroid carcinoma therapy.
AB  - Growing evidence supports the concept of oncogene dependence for cancer
      development; inhibition of the initiating oncogene can result in revertion of the
      neoplastic phenotype. The outstanding role of the RET proto-oncogene in the
      development of medullary thyroid carcinoma (MTC) is well established. With the
      emerging knowledge concerning the signal transduction pathways leading to
      subsequent neoplastic transformation, oncogenic activated RET becomes a highly
      attractive target for selective cancer therapy. A variety of novel approaches
      that target RET directly or indirectly have recently emerged and an increasing
      number are currently being assessed in clinical trials. In view of these
      findings, it becomes strikingly obvious that inhibition of RET oncogene function
      can be a viable option for the treatment of MTC. We summarize the current
      evidence for RET involvement in the etiology of MTC, and the therapeutic
      targeting of this process in preclinical and clinical studies.

PMID- 17019435
TI  - Rhabdomyosarcoma, Wilms tumor, and deletion of the patched gene in Gorlin
      syndrome.
AB  - BACKGROUND: A 5-year-old year girl with a medical history of mental retardation,
      physical abnormalities and a known interstitial deletion of chromosome 9q22-q32
      presented with a palpable suprapubic mass. During ultrasound investigation, a
      left renal mass was also detected. The patient underwent surgical removal of both
      neoplasms, which were diagnosed as a rhabdomyosarcoma and a Wilms tumor. Seven
      years later, she presented with macroglossia and a benign mandibular cyst.
      INVESTIGATIONS: Physical examination, karyotyping, abdominal and pelvic
      ultrasound, brain CT scan, anatomic pathology analysis with immunohistochemistry,
      and typing of polymorphic markers in the patched (PTCH) gene region. DIAGNOSIS:
      Gorlin syndrome with synchronous rhabdomyosarcoma and Wilms tumor. MANAGEMENT:
      Left nephrectomy, excision of paravesical tumor, excision of mandibular cysts,
      chemotherapy, and radiotherapy.

PMID- 17019436
TI  - On the possibility that H1 histone interaction with DNA occurs through phosphates
      connecting lysine and arginine side chain groups.
AB  - Gel filtration and velocity of sedimentation analyses on native and on lysine-
      and arginine-modified forms of the annelid worm Chaetopterus variopedatus sperm
      H1 histone indicate that anion-mediated lysine-arginine interactions play a
      relevant role in the stabilization of the oligomeric states of the molecule. CD
      spectroscopy shows that phosphate anions are at least an order of magnitude more
      efficient than chloride as negatively charged groups connecting H1 lysines and
      arginines. Acetylation of lysines, although not altering grossly the H1
      properties, causes a tenfold decrease of the structuring efficiency of
      phosphates. This suggests that DNA phosphates may be sandwiched between lysine
      and arginine groups of H1 histone when this molecule binds to chromatin,
      constituting a relevant parameter for the reciprocal stabilization of the protein
      and of the chromatin higher order structures.

PMID- 17019437
TI  - Novel peptide recognized by RhoA GTPase.
AB  - A phage-displayed random 7-mer disulfide bridge-constrained peptide library was
      used to map the surface of the RhoA GTPase and to find peptides able to recognize
      RhoA switch regions. Several peptide sequences were selected after four rounds of
      enrichment, giving a high signal in ELISA against RhoA-GDP. A detailed analysis
      of one such selected peptide, called R2 (CWSFPGYAC), is reported. The RhoA-R2
      interaction was investigated using fluorescence spectroscopy, chemical
      denaturation, and determination of the kinetics of nucleotide exchange and GTP
      hydrolysis in the presence of RhoA regulatory proteins. All measurements indicate
      that the affinity of the R2 peptide for RhoA is in the micromolar range and that
      R2 behaves as an inhibitor of: i) GDP binding to the apo form of RhoA (Mg2+-and
      nucleotide-free form of the GTPase), ii) nucleotide exchange stimulated by GEF
      (DH/PH tandem from PDZRhoGEF), and iii) GTP hydrolysis stimulated by the BH
      domain of GrafGAP protein.

PMID- 17019438
TI  - Methylotrophic extremophilic yeast Trichosporon sp.: a soil-derived isolate with
      potential applications in environmental biotechnology.
AB  - A yeast isolate revealing unique enzymatic activities and substrate-dependent
      polymorphism was obtained from autochthonous microflora of soil heavily polluted
      with oily slurries. By means of standard yeast identification procedures the
      strain was identified as Trichosporon cutaneum. Further molecular PCR product
      analyses of ribosomal DNA confirmed the identity of the isolate with the genus
      Trichosporon. As it grew on methanol as a sole carbon source, the strain appeared
      to be methylotrophic. Furthermore, it was also able to utilize formaldehyde. A
      multi-substrate growth potential was shown with several other carbon sources:
      glucose, glycerol, ethanol as well as petroleum derivatives and phenol. Optimum
      growth temperature was determined at 25 degrees C, and strong inhibition of
      growth at 37 degrees C together with the original soil habitat indicated lack of
      pathogenicity in warm-blooded animals and humans. The unusually high tolerance to
      xenobiotics such as diesel oil (>30 g/l), methanol (50 g/l), phenol (2 g/l) and
      formaldehyde (7.5 g/l) proved that the isolate was an extremophilic organism.
      With high-density cultures, formaldehyde was totally removed at initial
      concentrations up to 7.5 g/l within 24 h, which is the highest biodegradation
      capability ever reported. Partial biodegradation of methanol (13 g/l) and diesel
      fuel (20 g/l) was also observed. Enzymatic studies revealed atypical
      methylotrophic pathway reactions, lacking alcohol oxidase, as compared with the
      conventional methylotroph Hansenula polymorpha. However, the activities of
      glutathione-dependent formaldehyde dehydrogenase, formaldehyde reductase, formate
      dehydrogenase and unspecific aldehyde dehydrogenase(s) were present. An
      additional glutathione-dependent aldehyde dehydrogenase activity was also
      detected. Metabolic and biochemical characteristics of the isolated yeast open up
      new possibilities for environmental biotechnology. Some potential applications in
      soil bioremediation and wastewater decontamination are discussed.

PMID- 17019439
TI  - Detection of human papillomavirus in cervical cell specimens by hybrid capture
      and PCR with different primers.
AB  - The purpose of this study was to compare hybrid capture assay with PCRs using
      different primers for the L1, E6-E7 regions for the detection of human
      papillomavirus (HPV) genome. One hundred twenty-five cervical smears with normal
      (n=42) and abnormal (n=83) cytology were investigated. Those at high-risk for HPV
      were studied by hybridization antibody capture assay and PCR with the pU-1M/pU-2R
      primers. Target DNA from the HPV L1 region was amplified by SPF10 primer set and
      home-PCR with MY09/MY11 primers. The presence of HPV DNA in cervical smears was
      detected by SPF10 (in 72% of cases), MY09/MY11 (58%), hybrid capture (55%) and pU
      1M/pU-2R (39%). Results obtained with the SPF10 and MY09/MY11 consensus primer
      sets as well as hybrid capture and pU-1M/pU-2R specific for high-risk types
      differed significantly (chi2, P<0.0005). The correlation between assays with the
      use of SPF10 and MY09/MY11 was 86% and between hybrid capture and the pU-1M/pU2R
      technique--78%. In 49% of samples HPV DNA was detected by the four methods,
      whereas in 12% only by the SPF10 primers. The most sensitive technique was found
      to be PCR with the use of SPF10 primers, while the most specific--the MY09/11 PCR
      method. It seems that home-PCR with MY09/MY11 primers could be applied in
      screening tests.

PMID- 17019440
TI  - In situ detection of DNA and mRNA of human cytomegalovirus to distinguish
      different forms of viral infection in leukocytes.
AB  - In situ PCR and in situ reverse transcription PCR (RT-PCR) were applied to
      discriminate between latent and productive infection of human cytomegalovirus
      (HCMV) in leukocytes. We investigated 28 samples, in which viral pp65 antigen was
      detected only in the cytoplasm of leukocytes. Additionally we assayed 12
      specimens lacking pp65 antigen. Using nested PCR (nPCR), viral DNA was detected
      in 27 samples. In six samples the results of nPCR were unreadable due to the
      presence of polymerase inhibitors. By application of in situ PCR, we were able to
      confirm the presence of viral DNA in the nucleus and/or cytoplasm. Productive
      infection was recognized in 20 samples in which transcripts for late viral genes
      were detected. Among the 20 samples negative by in situ RT-PCR, we recognized
      phagocytosis of viral particles in eight and the latent form of HCMV infection in
      five.

PMID- 17019441
TI  - Assessment of various diagnostic methods of ureaplasma respiratory tract
      infections in newborns.
AB  - We compared three methods used microbial culturing for detection of ureaplasmas
      in endotracheal aspirate from 500 prematurely born neonates with respiratory
      disturbances: BioMerieux test, PCR and microbial culturing. Ureaplasmas were
      detected in respiratory tracts of 79 (16%) newborns. Correlation of the results
      of culture with those obtained with the BioMerieux kit, culture with PCR and
      BioMerieux kit with PCR was 97%, 89% and 90%, respectively. Sensitivity and
      specificity of PCR in comparison with culture was 86% and 98%, respectively, and
      of the BioMerieux kit 96% and 98%. PCR can be recommended in rapid diagnostics of
      respiratory infections in newborns suffering from respiratory disorders. It
      allows the detection of ureaplasmas in case of parallel infections and
      identification of their species.

PMID- 17019442
TI  - Analysis of oxygen binding by hemoglobin on the basis of mean intrinsic
      thermodynamic quantities.
AB  - The binding data for oxygenation of human hemoglobin, Hb, at various temperatures
      and in the absence and presence of 2,3-diphosphoglycerate, DPG, and inositol
      hexakis phosphate, IHP, were analyzed for extraction of mean intrinsic Gibbs free
      energy, DeltaGo, enthalpy, DeltaHo, and entropy, DeltaSo, of binding at various
      partial oxygen pressures. This method of analysis considers all the protein
      species present such as dimer and tetramer forms which were not considered by
      Imai et al. (Imai K et al., 1970, Biochim Biophys Acta 200: 189-196), in their
      analysis which was based on Adair equation. In this regard, the values of Hill
      equation parameters were estimated with high precision at all points of the
      binding curve and used for calculation of DeltaGo, DeltaHo and DeltaSo were also
      calculated by analysis of DeltaGo values at various temperatures using van't Hoff
      equation. The results represent the enthalpic nature of the cooperativity in Hb
      oxygenation and the compensation effect of intrinsic entropy. The interpretation
      of results also to be, into account the decrease of the binding affinity of sites
      for oxygen in the presence of DPG and IHP without any considerable changes in the
      site-site interaction (extent of cooperativity). In other words, the interactions
      between bound ligands, organic phosphates and oxygen, are more due to a
      decreasing binding affinity and not to the reduction of the cooperative
      interaction between sites. The results also document the more heterotropic effect
      of IHP compared to DPG.

PMID- 17019443
TI  - Characterization of disulfide exchange between DsbA and HtrA proteins from
      Escherichia coli.
AB  - DsbA is the major oxidase responsible for generation of disulfide bonds in
      proteins of E. coli envelope. In the present work we provided the first detailed
      characterization of disulfide exchange between DsbA and its natural substrate,
      HtrA protease. We demonstrated that HtrA oxidation relies on DsbA, both in vivo
      and in vitro. We followed the disulfide exchange between these proteins
      spectrofluorimetrically and found that DsbA oxidizes HtrA with a 1:1
      stoichiometry. The calculated second-order apparent rate constant (kapp) of this
      reaction was 3.3x10(4)+/-0.6x10(4) M-1s-1. This value was significantly higher
      than the values obtained for nonfunctional disulfide exchanges between DsbA and
      DsbC or DsbD and it was comparable to the kapp values calculated for in vitro
      oxidation of certain non-natural DsbA substrates of eukaryotic origin.

PMID- 17019444
TI  - Tocopherol esters inhibit human glutathione S-transferase omega.
AB  - Human glutathione S-transferase omega 1-1 (hGSTO1-1) is a newly identified member
      of the glutathione S-transferase (GST) family of genes, which also contains
      alpha, mu, pi, sigma, theta, and zeta members. hGSTO1-1 catalyzes the reduction
      of arsenate, monomethylarsenate (MMA(V)), and dimethylarsenate (DMA(V)) and
      exhibits thioltransferase and dehydroascorbate reductase activities. Recent
      evidence has show that cytokine release inhibitory drugs, which specifically
      inhibit interleukin-1b (IL-1b), directly target hGSTO1-1. We found that (+)-alpha
      tocopherol phosphate and (+)-alpha-tocopherol succinate inhibit hGSTO1-1 in a
      concentration-dependent manner with IC50 values of 2 microM and 4 microM,
      respectively. A Lineweaver-Burk plot demonstrated the uncompetitive nature of
      this inhibition. The molecular mechanism behind the inhibition of hGSTO1-1 by
      alpha-tocopherol esters (vitamin E) is important for understanding
      neurodegenerative diseases, which are also influenced by vitamin E.

PMID- 17019445
TI  - Malignant neoplasms--management in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of encounters at which malignant neoplasms were
      managed. This synopsis provides a backdrop against which the articles in this
      issue of Australian Family Physician can be further considered.

PMID- 17019446
TI  - Pain management in palliative care--an update.
AB  - BACKGROUND: Pain is a common and feared problem for those with advanced cancer.
      The goal of palliative care is to relieve suffering and improve quality of life.
      A step-by-step approach allows good symptom management and minimisation of drug
      side effects. OBJECTIVE: This article aims to improve the general practitioner's
      confidence in prescribing in the palliative care setting and to encourage early
      involvement of community palliative care teams. DISCUSSION: Opioid initiation and
      substitution, and the role of other medications and nondrug therapies in
      controlling cancer pain are discussed.

PMID- 17019447
TI  - Palliating symptoms other than pain.
AB  - BACKGROUND: Symptoms other than pain are a heavy burden for patients with either
      malignant or progressive nonmalignant disease and significantly reduce quality of
      life. OBJECTIVE: This article discusses the management of symptoms of malignant
      or progressive nonmalignant disease in the general practice setting. DISCUSSION:
      The approach to management of the symptoms of malignant or progressive
      nonmalignant disease is the same, regardless of the diagnosis. Management
      includes evaluation, treatment--depending on the underlying pathological
      mechanism, explanation for both the patient and their family, and ongoing review
      of goals of care.

PMID- 17019448
TI  - Suffering, loss and grief in palliative care.
AB  - BACKGROUND: The stress associated with advancing and incurable illness inevitably
      causes distress for patients, families and caregivers. A palliative approach to
      care aims to improve the quality of life for patients with a life limiting
      illness by reducing suffering through early identification, assessment and
      optimal management of pain, physical, cultural, psychological, social, and
      spiritual needs. OBJECTIVE: This article outlines some of the psychosocial issues
      in palliative care and offers communication strategies for general practitioners
      to use to elicit concerns. It also discusses anticipatory and complicated grief,
      and provides some useful resources. DISCUSSION: There is much that can be done by
      GPs, in collaboration with other services, to alleviate distress and suffering in
      people with a life limiting illness. In order to provide support for dying
      patients and their families, GPs also need to care for themselves.

PMID- 17019449
TI  - Palliative care for specific populations.
AB  - BACKGROUND: Ensuring access for all Australians to high quality palliative care
      requires an understanding of special considerations for specific populations,
      including children, older persons, and Indigenous Australians. OBJECTIVE: This
      article reviews some specific considerations for selected populations requiring
      palliative care. DISCUSSION: The complex clinical and support needs of children
      needing palliative care requires a well coordinated multidisciplinary team,
      inclusion of parents and siblings as part of the unit of care, and the use of
      developmentally appropriate communication strategies. Older people too may have
      different palliative needs. These include the need for careful assessment to
      ensure that reversible conditions, and emotional and existential concerns are not
      overlooked. Where the preferences and wishes of the person cannot be obtained,
      various clinical, ethical and legal principles will guide decisions. To ensure
      culturally appropriate care is provided to Indigenous Australians requiring
      palliative care, both Indigenous organisations and people should be included in
      the planning and provision of care.

PMID- 17019450
TI  - The role of physiotherapy in palliative care.

PMID- 17019451
TI  - Complementary medicine in palliative care.
AB  - This is the eighth of a series of articles looking at the available evidence for
      complementary medicine relating to the theme topic in Australian Family
      Physician. For patients facing an incurable and life threatening illness such as
      cancer, decisions that lead to the use of complementary and alternative medicines
      (CAM) are often seen as pragmatic and a last resort when mainstream medicine has
      nothing left to offer.

PMID- 17019452
TI  - Managing skin cancer below the knee.
AB  - CASE STUDY: Mr RR, 74 years of age, developed a nodule on his lower right leg in
      mid 2005. He was offered the option of excision, skin graft and 10 days bed stay
      with elevation at a private hospital, but declined due to the cost. He was then
      referred to a major urban cancer institute for opinion. He was advised that the
      nodule would most likely fall off and that a 'watch and wait' approach was
      indicated. Presumably there was a clinical diagnosis of keratoacanthoma.

PMID- 17019453
TI  - Localised herpes zoster infection and SIADH.
AB  - Localised herpes zoster infection ('shingles') in older patients is a common
      presentation to primary, and sometimes secondary, care physicians. However,
      symptoms of hyponatraemia, caused by the rare complication of 'syndrome of
      inappropriate antidiuretic hormone secretion' (SIADH), may be mistaken for
      constitutional symptoms of the infection itself. Such patients may require closer
      monitoring or hospitalisation.

PMID- 17019454
TI  - Intimate partner violence in deviant settings--complex needs of women survivors.
AB  - BACKGROUND: Women experiencing intimate violence within deviant settings,
      including bikie and other gangs and cults, have recently been the focus of
      research in South Australia. Domestic violence shelters are seeing increasing
      numbers of these women who are often involved in high risk behaviour and/or
      situations that pose significant risk to themselves and any accompanying
      children. OBJECTIVE: This article provides an overview of the profiles of women
      (and their children) escaping intimate partner violence within deviant settings,
      and the range of complex physical and mental health needs medical practitioners
      are likely to encounter in these patients. DISCUSSION: Specific women's histories
      of ritualised partner abuse, its cultural context, and the resultant physical and
      mental health issues for these women and their children is discussed. It provides
      strategies for practitioners to work with these women and their children to
      overcome existing barriers to clinical intervention.

PMID- 17019455
TI  - Men who have sex with men--a management approach for GPs.
AB  - BACKGROUND: At least one in 20 Australian men report sexual contact with another
      man in their lifetime. Men who have sex with other men have higher rates of
      sexually transmitted infections, and are more likely to experience mental health
      problems and use recreational drugs and alcohol. OBJECTIVE: This article
      describes the health problems and sexual behaviour of men who have sex with men
      and provides an outline and an approach to discussing sexuality in general
      practice. DISCUSSION: Sexuality can be difficult to discuss in general practice.
      A nonjudgmental approach to men who have sex with men may facilitate early
      identification of the relevant health issues.

PMID- 17019456
TI  - Bisphosphonates and osteonecrosis of the jaw.
AB  - Recently an association between bisphosphonate use and a rare dental condition
      termed 'osteonecrosis of the jaw' (ONJ) has been reported. Patients with
      osteoporosis and Paget disease who take bisphosphonates have a significantly
      reduced risk of fracture and other skeletal complications. This represents
      significant health benefits, against which the small risk of ONJ needs to be
      considered. In patients with bone malignancy, the risk of ONJ needs to be
      balanced against the benefit of therapy on the underlying malignancy. There are
      still many uncertainties about this condition. This position paper seeks to
      summarise what is currently known about ONJ to provide information to medical
      practitioners and dental practitioners.

PMID- 17019457
TI  - Diagnostic challenge--is this really a stroke?
AB  - BACKGROUND: Although acute stroke most commonly presents with hemiparesis, facial
      weakness and dysphasia, these symptoms can sometimes be the atypical
      presentations of other conditions which may be difficult to diagnose. OBJECTIVE:
      This article presents three cases of stroke mimics and discusses how to improve
      accuracy in diagnosing stroke in the primary care setting. DISCUSSION: Stroke is
      a medical emergency and urgent hospital transfer is vital. Hypoglycaemia,
      hyperglycaemia, epilepsy, multiple sclerosis, hemiplegic migraine, intracranial
      tumours or infection (meningitis/encephalitis/abscess) can all mimic stroke. The
      Los Angeles Prehospital Stroke Screen (LAPSS) consists of four history items, a
      blood glucose measure, and three examination items designed to detect unilateral
      motor weakness. It can be utilised to improve the accuracy in diagnosing stroke
      and stroke mimics in general practice.

PMID- 17019458
TI  - Chronic paronychia--putting a finger on the evidence.
AB  - At first glance it seemed a minor problem, but the look on my new patient's face
      suggested otherwise. His finger had been painful for months and this week it had
      become worse. His swollen, erythematous nail fold, absent cuticle, and mildly
      dystrophic nail painted a typical picture of chronic paronychia. Assuming an
      acute bacterial superinfection, I prescribed a course of antibiotics, but my
      patient needed advice on treatment of the underlying condition. Another general
      practitioner had arranged fungal cultures, which had grown candida. Would
      antifungals be the best treatment? My patient and I agreed to meet in a week to
      assess his response to the antibiotics and to discuss treatment of the underlying
      chronic paronychia.

PMID- 17019459
TI  - Endocrinology and the skin.
AB  - CASE STUDY: 'I've got these ugly red blotches on my legs and they are getting
      worse?' Lisa, 32 years of age, is an accountant who always presents herself
      meticulously. You can understand why she doesn't like the raised red brown
      blotches on her shins. The lesions are raised, indurated with follicular
      accentuation. They are an uneven red-brown colour that doesn't fade with
      pressure, nor does the tissue pit. Lisa seems more upset and agitated than you
      expected. When you ask if she's under stress at work she breaks down in tears and
      says she feels 'agitated and on edge all the time and can't sit still for a
      minute'.

PMID- 17019460
TI  - Advance health directives.
AB  - Case histories are based on actual medical negligence claims or medicolegal
      referrals, however, certain facts have been omitted or changed by the author to
      ensure the anonymity of the parties involved. The aim of this article is to
      outline the legislative framework in relation to advance health directives and
      enduring powers of attorney or guardianship, with a particular focus on the
      medical and legal issues of relevance with respect to an assessment of mental
      capacity.

PMID- 17019461
TI  - Minor skin excisions in general practice in North Queensland.
AB  - OBJECTIVE: To describe the demographics of patients presenting with skin cancer
      to general practitioners in rural North Queensland, the sites from which skin
      cancers are removed, and their histology. METHODS: Data was recorded from 1247
      consecutive patients who attended for minor skin lesion excisions. RESULTS: Close
      to half (46.7%) of lesions excised were skin cancers. We excised more squamous
      cell carcinomas than basal cell carcinomas (0.74:1). Our number needed to treat
      (benign or dysplastic naevi excised per melanoma) was 8.4. Mean age for excision
      of melanoma, basal cell carcinoma and squamous cell carcinoma was 55, 60.9 and
      63.8 years respectively. Relative tumour density was greatest in the face, scalp
      and neck region for all skin cancers. DISCUSSION: In this sample of Mackay GPs,
      there was a very high yield of skin cancers from all excisions. We could consider
      lowering our threshold for excision of pigmented lesions.

PMID- 17019462
TI  - Training the primary care team--a successful interprofessional education
      initiative.
AB  - BACKGROUND: A multidisciplinary approach to the education of health professionals
      is being increasingly promoted as a means to cultivate collaborative practice
      between professions in the health care sector and to enhance patient care.
      METHOD: One hundred and two students from seven different University of
      Queensland Health Science disciplines completed between one and three
      interprofessional seminars involving small group work, case discussion, expert
      panel presentation, and interactive question and answers. RESULTS: Paired sample
      T testing indicated significant differences in pre- and post-responses related to
      knowledge of effective clinical management, multidisciplinary assessment, goal
      setting, roles and responsibilities, and referral networks across all
      disciplines. Similar testing also indicated significant shifts in attitude to
      increased job satisfaction, reduced fragmentation of care, and reduction in
      professional boundaries related to multidisciplinary care. Ninety-six percent of
      participants indicated that the benefit of a team approach was effectively
      modelled. DISCUSSION: Undergraduate interprofessional education can result in
      highly significant shifts in knowledge of, and attitudes to, multidisciplinary
      team care.

PMID- 17019464
TI  - Cyclometalated iridium(III)-sensitized titanium dioxide solar cells.
AB  - Ir(III) dyes used as sensitizers in dye-sensitized solar cells produced quantum
      yields approaching unity for conversion of absorbed photons to current under
      simulated air mass 1.0 sunlight, with current production resulting from ligand-to
      ligand charge-transfer states, rather than the typical metal-to-ligand charge
      transfer states in ruthenium-based cells.

PMID- 17019465
TI  - Stilbene analogs in Hula-twist photoisomerization.
AB  - Photoisomerization of several cis- or Z-stilbene analogs and two E-analogs in low
      temperature organic glasses was examined. From a mechanistic view-point, the
      compounds can be divided into three types: (i) those giving identical Hula-twist
      (HT) and one-bond-flip (OBF) products, (ii) those giving a single HT product that
      is different (hence distinguishable) from the OBF product and (iii) those showing
      two distinct HT processes but only one OBF process. Examples for all three types
      of analogs are provided emphasizing the most informative Type-II (stilbene
      analogs with identical but unsymmetrically substituted phenyl rings), including
      linear as well as conformationally constrained compounds. Conditions necessary
      for establishing HT and OBF processes are defined. Proper choice and design of
      model systems are essential for establishing or eliminating HT mechanism(s) of
      isomerization.

PMID- 17019466
TI  - The photochemistry and photophysics of all-trans-1,4-diindanylidenyl-2-butene, a
      rigid analogue of all-trans-1,6-diphenyl-1,3,5-hexatriene.
AB  - all-trans-1,4-Diindanylidenyl-2-butene (ttt-stiff-5-DPH), a torsionally
      constrained analogue of all-trans-1,6-diphenyl-1,3,5-hexatriene (ttt-DPH), was
      synthesized and studied in order to evaluate the role of phenyl-vinyl torsional
      motions in the photophysical and photochemical responses of the DPH chromophore.
      Spectroscopic and photoisomerization measurements reveal that the behavior of the
      rigid DPH analogue is very similar to that of the parent DPH. This similarity is
      obtained despite the fact that the alkyl substitution from the five-membered
      rings selectively lowers the energy of the 1 (1)B(u)* state, leading to inversion
      of the order of the 1 (1)B(u)* and 2 (1)A(g)* energy levels in hydrocarbon
      solvents. In stiff-5-DPH, as in DPH, an increase in solvent polarity enhances
      terminal over central bond photoisomerization. Analyses of fluorescence and
      photoisomerization quantum yields show that, as in DPH, the torsional relaxation
      channel on the singlet excited state manifold is inefficient, falling far short
      of accounting for all radiationless decay. Significant (approximately 50 and 80%
      of all singlet decay in Bz and AN, respectively), photochemically unproductive,
      radiationless decay channels exist in both molecules. Competing one bond
      photoisomerizations give the two major photoproducts: tct-stiff-5-DPH and ctt
      stiff-5-DPH. They were isolated in pure form and were spectroscopically
      characterized. Biacetyl-sensitization was used to study the behavior of the stiff
      5-DPH triplet state. As in the parent DPH, stiff-5-DPH triplets undergo
      relatively efficient concentration dependent geometric photoisomerization.

PMID- 17019467
TI  - Combinatorial fluorescence energy transfer molecular beacons for probing nucleic
      acid sequences.
AB  - We report the design, synthesis, and characterization of molecular beacons (MB)
      consisting of three distinct fluorophores, 6-carboxyfluorescein (Fam), N,N,N',N'
      tetramethyl-6-carboxyrhodamine (Tam), and Cyanine-5 (Cy5). The primary light
      absorber/energy donor (Fam) is located on one terminus of the MB, whereas the
      primary energy acceptor/secondary donor (Tam) and secondary acceptor (Cy5) are
      located at the other terminus of the MB. In the absence of target DNA or RNA, the
      MB exists in the stem-closed form. Excitation of Fam initiates an energy transfer
      cascade from Fam to Tam and further to Cy5 generating unique fluorescence
      signatures defined as the ratio of the emission from each of the three
      fluorophores. This energy transfer cascade was investigated in detail by steady
      state and time-resolved fluorescence spectroscopy, as well as fluorescence
      depolarization studies. In the presence of the complementary target DNA, the MB
      opened efficiently and hybridized with the target separating Fam and Tam by a
      large distance, so that energy transfer from Fam to Tam was blocked in the stem
      open form. This opening of the MB generates a "bar code" fluorescence signature,
      which is different from the signature of the stem-closed MB. The fluorescence
      signature of this combinatorial fluorescence energy transfer MB can be tuned by
      variation of the spacer length between the individual fluorophores.

PMID- 17019468
TI  - Cis-->trans and trans-->cis isomerizations of styrylcoumarins in the solid state.
      Importance of the location of free volume in crystal lattices.
AB  - We have examined the photobehavior of a set of isomers of 2-pyranone-annulated
      stilbenes (6-styrylcoumarin 1, 7-styrylcoumarin 2, 4-methyl-6-styrylcoumarin 3,
      and 4-methyl-7-styrylcoumarin, 4) in their crystalline phases. While the cis
      isomers of 1-3 undergo cis-->trans photoisomerizations in the solid state, cis-4
      and the trans isomers of 1-3 do not; the trans isomer of 4 undergoes photo
      induced intermolecular reactions. Solution-state irradiations of the trans
      isomers of 1-4 lead to the cis isomers quite readily, as does cis-4 lead to trans
      4, which suggests that the absence of geometric isomerization of the trans
      isomers and the lack of reactivity of cis-4 in the solid state are due to
      molecular packing effects. X-Ray crystal structural analyses of 1-4 reveal
      interesting conformational preferences for the styrenic moieties and differences
      in the total 'free' volumes within the lattices, but neither factor explains
      satisfactorily why some of the molecules undergo geometric isomerizations in
      their single crystals and others do not. Using the PLATON program, we have
      located the sizes and positions of 'void volumes' within the crystal lattices,
      and identified trajectories necessary for atomic motions to lead to geometric
      isomerizations to understand the reactivities of 1-4. The voids in the reactive
      cis isomers of 1-3 crystals are located along the trajectories needed for
      geometric isomerization. The relevant voids in the crystals of cis-4 and the
      trans isomers of 1 and 2 (the non-isomerizing molecules for which suitable
      crystals could be grown for X-ray analyses) are located along a trajectory that
      does not permit isomerization. We hypothesize that the classical momentum gained
      from the initial motions that are facilitated due to the voids in the crystals of
      the cis isomers of 1-3, as well as the heat dissipated to the local environment
      by internal conversions and vibronic cascade of the Franck-Condon states, helps
      to drive the system over potential energy barriers that would not be possible
      otherwise. Cis-4 and the trans isomers of 1 and 2, as well as other examples from
      the literature in which geometric isomerizations do or do not occur in the solid
      state, also follow the predictions based upon the PLATON analyses. On these
      bases, it is suggested that the methodology described may be generally applicable
      for predicting when geometric isomerizations (and possibly other reactive
      processes) in crystalline materials will occur.

PMID- 17019469
TI  - Electronic structures of intermolecular charge-transfer states in fast electron
      transfers with tetrathiafulvalene donor. Thermal and photoactivation of [2 + 4]
      cycloaddition to o-chloranil acceptor.
AB  - Tetrathiafulvalene (TTF) spontaneously forms a series of unusual charge-transfer
      complexes with various quinonoid acceptors such as o-chloranil (CA) that show
      pronounced near-IR absorption (lambda(CT) = 1100 nm). The successful isolation of
      the corresponding [1 : 1] donor-acceptor complex from solution and X-ray
      crystallographic analysis at low temperatures reveal the polarized charge
      transfer state: [TTF(q+),CA(q-)] with high degree of charge-transfer (q = 0.6),
      which is spectrally and crystallographically distinguished from the separate
      redox (ion-pair) state: [TTF(+*) + CA(-*) ]. The unique interconversion of charge
      transfer and electron-transfer states is theoretically well-accommodated by
      Mulliken theory using semi-empirical valence-bond and molecular-orbital
      methodologies. Mechanistic implications are discussed of both the thermally
      activated and the photochemically promoted processes via fast (intracomplex)
      electron transfer followed by collapse of the adiabatic and the non-adiabatic
      (vibrationally-excited) ion-pairs, respectively, to the [2 + 4] cycloadduct of
      tetrathiafulvalene and o-chloranil.

PMID- 17019470
TI  - Templating photodimerization of stilbazoles with water-soluble calixarenes.
AB  - Water soluble six and eight membered calixarenes template the dimerization of
      trans-stilbazoles. In the absence of calixarenes at the concentrations employed
      stilbazoles mainly isomerize to the corresponding cis isomers. Calixarenes help
      to localize the olefins and orient them in a specific geometry to yield anti-head
      tail dimers. Electrostatic interaction between the sulfonate anion and the
      pyridinium ion of the olefin and hydrophobic interaction between the olefin and
      the host cavity are believed to be responsible for the observed selectivity. (1)H
      NMR spectra provide evidence for complexation but do not suggest the exact
      structure of the host-guest complex.

PMID- 17019471
TI  - Supramolecular photochemical self-assemblies for fluorescence "turn on" and "turn
      off" assays for chem-bio-helices.
AB  - We describe the development of an optical sensing system for the high-throughput
      screening (HTS) of a broad range of biological molecules, whole cells, organisms
      and pathogens, and illustrate the technology applications by a hyaluronidase
      enzyme activity assay as a specific example. At the core of the technology
      described in this paper, is the exciton concept that is relevant to molecular
      aggregation. J-aggregates of cyanine dyes have a narrower, red-shifted absorption
      band compared to monomer. We demonstrate that self-assembly may be driven by the
      helicogenic nature of the cyanine dye, converting the linear polymers of
      hyaluronic acid or carboxymethyl cellulose into supramolecular helical
      assemblies. This self-assembly is accompanied by an intense, sharp, red-shifted J
      aggregate fluorescence. We utilized this property to develop an assay for the
      enzyme hyaluronidase, based upon the concept of "scaffold destruction," whereby
      the disruption/destruction of the hyaluronic acid polymer by hyaluronidase is
      accompanied by an attenuation of light emission from the J-aggregate. The extent
      of light attenuation provides an index of hyaluronidase activity. Other polymers
      of carbohydrates, proteins, nucleic acids and chemical polymers (such as the
      carbon nanotube) might provide a similar scaffold for helicogenic dyes upon which
      molecular aggregation can occur. A key feature of these assays is that they are
      label-free.

PMID- 17019472
TI  - On the mechanism of nitrogen photofixation at nanostructured iron titanate films.
AB  - The photofixation of dinitrogen to ammonia at a nanostructured iron titanate thin
      film, prepared from iron(III) chloride and titanium tetraisopropylate, was
      established by isotopic labeling employing (15,15)N(2). It is found that traces
      of iron chloride in the film are required to observe significant amounts of
      ammonia. It is therefore proposed that the photogenerated hole oxidizes chloride
      to an adsorbed chlorine atom and the latter subsequently oxidizes ethanol, the
      reducing agent necessary for ammonia formation. However, thin films obtained from
      a chloride-free precursor like iron tris-acetylacetonate are also active. Upon
      prolonged irradiation ammonia is oxidized to nitrate by traces of oxygen. It is
      found that this final reaction step does not require photoexcitation of the iron
      titanate thin film but occurs thermally. Titania films exhibit about the same
      catalytic activity in ammonia oxidation whereas iron oxide films are much less
      active. Contrary to this thermal reaction step, the reduction of intermediate
      hydrazine by ethanol occurs only photochemically.

PMID- 17019473
TI  - Switch between charge transfer and local excited states in 4-aminophenyl
      substituted Hantzsch 1,4-dihydropyridine induced by pH change and transition
      metal ions.
AB  - The absorption and fluorescence spectra of a Hantzsch 1,4-dihydropyridine
      derivative bearing a N,N-dimethylaminophenyl group at 4-position (H(2)Py
      PhN(CH(3))(2)) in aprotic solvents have been examined and compared to model
      compounds 4-phenyl- and 4-methyl-substituted Hantzsch 1,4-dihydropyridines
      (H(2)Py-Ph and H(2)Py-Me). While H(2)Py-Ph and H(2)Py-Me show fluorescence around
      420 nm from the local excited state of the dihydropyridine chromophore, H(2)Py
      PhN(CH(3))(2) exhibits fluorescence around 520 nm from the intramolecular charge
      transfer (ICT) state involving the aniline and dihydropyridine groups as donor
      and acceptor, respectively. Upon addition of an acid to the solution of H(2)Py
      PhN(CH(3))(2), the amino group in the aniline is protonated. Thus, the
      photoinduced intramolecular charge transfer is prevented, and only the
      fluorescence from the local excited state of the dihydropyridine chromophore can
      be detected. These changes in the fluorescence behavior are fully reversible:
      subsequent addition of a base to the acidic solution leads to the recovery of the
      ICT fluorescence and the quenching of the local fluorescence. Transition metal
      ions also can switch the fluorescence of H(2)Py-PhN(CH(3))(2). Evidence for the
      interaction between transition metal ions and the amino group in the
      dimethylaniline have been provided by absorption and emission spectrum as well as
      NMR studies.

PMID- 17019474
TI  - Vacuum-ultraviolet photochemically initiated modification of polystyrene
      surfaces: morphological changes and mechanistic investigations.
AB  - Vacuum-ultraviolet (VUV) irradiation (lambda(exc): 172 +/- 12 nm) of polystyrene
      films in the presence of oxygen produced not only oxidatively functionalized
      surfaces, but generated also morphological changes. Whereas OH- and C=O
      functionalized surfaces might be used for e.g. secondary functionalization,
      enhanced aggregation or printing, processes leading to morphological changes open
      new possibilities of microstructurization. Series of experiments made under
      different experimental conditions brought evidence of two different reaction
      pathways: introduction of OH- and C=O-groups at the polystyrene pathways is
      mainly due to the reaction of reactive oxygen species (hydroxyl radicals, atomic
      oxygen, ozone) produced in the gas phase between the VUV-radiation source and the
      substrate. However, oxidative fragmentation leading to morphological changes,
      oxidation products of low molecular weight and eventually to mineralization of
      the organic substrate is initiated by electronic excitation of the polymer
      leading to C-C-bond homolysis and to a complex oxidation manifold after trapping
      of the C-centred radicals by molecular oxygen. The pathways of oxidative
      functionalization or fragmentation could be differentiated by FTIR-ATR analysis
      of irradiated polystyrene surfaces before and after washing with acetonitrile and
      microscopic fluorescence analysis of the surfaces secondarily functionalized with
      the N,N,N-tridodecyl-triaza-triangulenium (TATA) cation. Ozonization of the
      polystyrene leads to oxidative functionalization of the polymer surface but
      cannot initiate the fragmentation of the polymer backbone. Oxidative
      fragmentation is initiated by electronic excitation of the polymer (contact-mode
      AFM analysis), and evidence of the generation of intermediate C-centred radicals
      is given e.g. by experiments in the absence of oxygen leading to cross-linking
      (solubility effects, optical microscopy, friction-mode AFM) and
      disproportionation (fluorescence).

PMID- 17019475
TI  - Photoelectropolymerization of aniline in a dye-sensitized solar cell.
AB  - A dye-sensitized solar cell was constructed using a porphyrin photosensitizer
      and, in place of the usual iodide redox system, a solution in aniline solvent
      containing lithium perchlorate electrolyte, camphorsulfonic acid, and
      poly(ethylene oxide) copolymer. Irradiation generated polyaniline within the
      cell, initially following a proposed photoelectropolymerization mechanism, and
      eventually operating as a solar cell with polyaniline as the hole transport
      medium. Overall energy conversion efficiency was 0.8% at moderate light
      intensities (14.6 mW cm(-2)) but lower at higher light intensities due to
      conductivity limitations.

PMID- 17019476
TI  - Flavin-induced photodecomposition of sulfur-containing amino acids is decisive in
      the formation of beer lightstruck flavor.
AB  - Photooxidation of sulfur-containing amino acids and derivatives readily occurs
      upon visible-light irradiation in the presence of flavins. The sulfur moiety
      seems pivotal for interaction, as was determined from kinetic analyses using
      laser flash photolysis spectroscopy. After photooxidation, the resulting radical
      intermediates were characterized by addition to a spin trap, followed by electron
      paramagnetic resonance spectroscopy and evaluation of the coupling constants. The
      presence of the proposed radical intermediates was strongly supported by the
      identification of the reaction products using mass spectrometry. Accordingly,
      feasible degradation pathways for various sulfur-containing amino acids and
      derivatives were proposed. It was finally proven that flavin-induced
      photoproduction of sulfhydryl radicals and recombination with a 3-methylbut-2
      enyl radical, derived from the photodegradation of hop-derived isohumulones, are
      decisive in the formation of beer lightstruck flavor.

PMID- 17019477
TI  - The inter-relationship between triplet energies and spin chemistry.
AB  - Triplet energies play a considerable role in optical spectroscopy, and can be
      determined from phosphorescence or the quenching thereof. Their role in spin
      chemistry may not be as obvious, but the triplet state has always had an
      important function or utility, namely of reaction intermediates such as radical
      pairs, their precursors, of carbenes, and of the final products. In situ NMR
      spectroscopy represents a useful tool to explore certain properties of the
      triplet state, especially in cases with no phosphorescence. The 'phase' of CIDNP
      resonances, i.e., emission or enhanced absorption, reflects the spin selectivity
      of electron transfer reactions. In radical ion pairs the spin selectivity is
      determined by the relation between the change of the standard free enthalpy
      DeltaG degrees during the electron back transfer and the triplet energies (E(T))
      of the products. If triplet recombination is energetically feasible (DeltaG
      degrees > E(T)), it is typically the more efficient process in agreement with the
      Marcus theory.

PMID- 17019478
TI  - Academy of Science survey of research publishing in SA - the SAMJ streaks ahead.

PMID- 17019479
TI  - Rocephin--the thin end of the wedge.

PMID- 17019480
TI  - Country of residence and deaths among medical graduates from the Malawi College
      of Medicine, 1992-2002.

PMID- 17019481
TI  - Vegetable and fruit consumption--are the health benefits sufficiently
      appreciated?

PMID- 17019482
TI  - State surgeons get the cruellest cut.

PMID- 17019483
TI  - Polio vaccination 'gaps'--Namibia pays the price.

PMID- 17019484
TI  - AIDS heel-dragging: 'enough!' cry top clinicians.

PMID- 17019485
TI  - 'Tik' causing a health crisis.

PMID- 17019486
TI  - Rural health and transformation in South Africa.

PMID- 17019487
TI  - Echinococcosis--a rare spinal disorder.

PMID- 17019488
TI  - Chondral fracture of the femoral trochlea.

PMID- 17019489
TI  - Anticoagulation in South Africa--a dangerous necessity.

PMID- 17019490
TI  - Use of generic alendronate in the treatment of osteoporosis.

PMID- 17019491
TI  - Inappropriateness of antimicrobial prescription in private primary health care
      settings in South Africa.

PMID- 17019492
TI  - Implementation of single-dose nevirapine for prevention of MTCT of HIV--lessons
      from Cape Town.

PMID- 17019493
TI  - Thrombo-embolic and bleeding complications in patients with mechanical valve
      replacements--a prospective observational study.
AB  - BACKGROUND AND OBJECTIVES: Long-term anticoagulation therapy is essential to
      prevent thrombo-embolic events in patients with mechanical valve replacements. In
      order to offer indigent patients mechanical heart valve replacement surgery,
      dedicated anticoagulation clinics are necessary for follow-up. This study
      assessed the safety and efficacy of lifelong oral anticoagulation therapy in
      Johannesburg General Hospital mechanical heart valve replacement recipients. The
      incidence of bleeding and thrombo-embolic complications was documented in three
      groups of patients with mechanical valve replacements. The groups included
      patients with aortic valve replacements (AVRs), mitral valve replacements (MVRs)
      and double (aortic and mitral) valve replacements (DVRs). MATERIALS AND METHODS:
      A prospective observational study was conducted over a 4-month period. Data on
      306 patients attending the Johannesburg General Hospital anticoagulation clinic
      between 2000 and 2005 were analysed. Of the total patients selected, 205 were
      assigned to the mechanical valve replacement group (which included 63 patients
      with AVRs, 93 with MVRs and 49 with DVRs); a control group of 101 nonmechanical
      valve replacement patients were also included. At each visit the level of
      anticoagulation was assessed from the international normalised ratio (INR)
      values, and the presence of bleeding and/or thrombo-embolic complications was
      documented. RESULTS: There were a total of 51 bleeding and thrombo-embolic
      complications in the study population. Patients with DVRs had a higher proportion
      of combined complications (30.61%) than patients with single valve replacements
      (14.29% in the AVR group and 18.05% in the MVR group) and patients in the control
      group (12.87%). There were 38 bleeding complications, 30 minor and 8 major.
      Twelve thrombo-embolic events were documented. Individually, there was no
      significant difference in thrombo-embolic and bleeding complications between the
      subgroups. Eighty-two per cent of patients in the mechanical valve replacement
      group were within the therapeutic range for anticoagulant control (INR 2.5-3.5)
      v. 54% in the control group (INR 2.0-3.0). Anticoagulant control was of a high
      quality and was not a contributing factor to the incidence of bleeding and/ or
      thrombo-embolic complications. CONCLUSION: The finding of a low incidence of
      bleeding and thrombo-embolic complications in patients with mechanical valve
      replacements supports the continued placement of mechanical valves in our setting
      and use of oral anticoagulation therapy at an INR of 2.5-3.5. However the
      increased risk of both bleeding and thrombo-embolic complications in the DVR
      group is cause for great concern and warrants further investigation.

PMID- 17019494
TI  - Staphylococcus aureus bacteraemia at two academic hospitals in Johannesburg.
AB  - OBJECTIVES AND METHODS: Staphylococcus aureus bacteraemia (SAB) remains a major
      problem worldwide. A retrospective study of patients with SAB seen from November
      1999 to October 2002 was conducted at two academic hospitals in Johannesburg to
      determine mortality rates (death within 14 days of submission of blood culture)
      in patients bacteraemic with methicillin-sensitive (MSSA) and resistant S. aureus
      (MRSA) and to identify risk factors associated with mortality. RESULTS: Of 449
      patients with SAB, 104 (23.2%) died within 14 days of clinically suspected SAB.
      Of the 204 patients who acquired SAB in hospital, 6 patients died within 2 days,
      39 between 2 and 14 days, and 41 more than 14 days after onset of SAB. One
      hundred and five patients (23.4%) had MRSA bacteraemia, 21 (20%) originating from
      the community. The MRSA bacteraemia rate among patients with hospital-acquired
      infection was 41.1%, significantly higher (p < 0.0001) than the 10.3% community
      acquired MRSA bacteraemia. Thirty-five (33.3%) of the 105 patients with MRSA
      bacteraemia died within 14 days, compared with 69 (20.1%) of 344 MSSA patients (p
      = 0.0048). Admission to the intensive care unit (ICU) was significantly
      associated with mortality (p < 0.001)--30 of 79 patients admitted to ICU died
      (38%). Among 222 patients whose HIV status was known, 117 (52.7%) were positive,
      and of these 32 died (27.4%), a rate not significantly higher than that among HIV
      seronegative patients (18 of 105 patients, p = 0.69). CONCLUSIONS: Compared with
      MSSA, MRSA was shown to be significantly associated with mortality. Stay in ICU
      and infection with strains resistant to oxacillin, ofloxacin and rifampicin were
      highly significant predictors for mortality.

PMID- 17019495
TI  - Management of older patients presenting after a fall--an accident and emergency
      department audit.
AB  - BACKGROUND: It is common for older patients to present to accident and emergency
      (AE) departments after a fall. Management should include assessment and treatment
      of the injuries and assessment and correction of underlying risk factors in order
      to prevent recurrent falls. OBJECTIVES: To determine management of older patients
      presenting after a fall to the AE department of Groote Schuur Hospital in Cape
      Town, South Africa. METHOD: Hospital records were reviewed for a random sample of
      100 patients aged 65 years and older presenting to the AE department after a
      fall, between December 2001 and May 2002. RESULTS: The mean age of the sample was
      78.6 years (range 65-98 years); 72% of subjects were female. History of a
      previous fall, and history of drug or alcohol intake, were recorded in less than
      20% of cases. Blood pressure and pulse rate were recorded in approximately 90% of
      cases, and pulse rhythm and postural blood pressure in 2%. Examination of the
      musculoskeletal system was done in 86% of cases and that of other systems in less
      than 50%; cognitive assessment was conducted in less than 30%. Radiological
      investigations were performed in 89% of cases, glucose and haemoglobin in 32%,
      renal profile and electrocardiogram in 5%, and urinalysis in 4%. Three-quarters
      of the patients were referred for further management: 52% to orthopaedic surgery,
      12% to other surgical subspecialties, 6% to the general medical department, and
      6% to other hospitals and clinics. No referrals were made to geriatric medicine,
      physiotherapy or occupational therapy. CONCLUSIONS: In managing elderly patients
      after a fall, the AE department focused on injuries sustained. Little effort was
      made to establish and manage risk factors, hence to prevent recurrent falls.
      Guidelines are needed for the management of such patients in AE departments.

PMID- 17019497
TI  - SAGES/SASES/SAGINS/SASPEN Congress 2006, 5 - 9 August 2006, Feather Market
      Centre, Port Elizabeth.

PMID- 17019498
TI  - 10th Annual Conference on Rural Health - 10 & 11 August 2006, Empangeni, KwaZulu
      Natal.

PMID- 17019496
TI  - A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced
      lactic acidosis in HIV-infected patients in a South African context.
AB  - OBJECTIVE: To determine the incidence of and predisposing risk factors for lactic
      acidosis in HIV-infected patients on antiretroviral drugs in South Africa.
      DESIGN: Observational case series. SETTING: Sinikithemba HIV Clinic, McCord
      Hospital, Durban. SUBJECTS: Eight hundred and ninety-one HIV-positive patients on
      highly active antiretroviral therapy (HAART) during an 18-month period commencing
      in January 2004. MEASUREMENTS AND RESULTS: Fourteen cases of lactic acidosis
      (incidence rate of 19 (95% confidence interval (CI): 9-29) cases per 1,000 person
      years of treatment) were reported. All cases were female, with a median age of 36
      years and a median weight of 81 kg. The median time on HAART before developing
      lactic acidosis was 7.5 months and the median peak lactate level was 9.3 mmol/l.
      All cases were on stavudine (d4T), lamivudine (3TC) and 1 non-NRTI. The case
      mortality rate was 29% (4 patients). CONCLUSIONS: The incidence rate is higher
      than reported in studies in developed countries. This may be due to d4T, which is
      recommended as a first-line antiretroviral drug in South Africa. This implication
      raises the question whether it is an appropriate drug in first-line treatment of
      patients with predisposing risk factors such as female gender and being
      overweight.

PMID- 17019499
TI  - Isolation to interface to integration - is it feasible to seek a holistic
      profession?
AB  - OBJECTIVES: Over thirty years both divergence and synergy have been seen in the
      health informatics (HI) domain; to the point where aspiration is towards a
      collective environment recognising HI as a mature discipline internationally. The
      author considers catalysts and inhibitors to this goal over 30 years, and asks
      the question - is one professional identity achievable and desirable? This review
      of development of HI aims to promote reflection of the status, value and
      attributable influence with a view to recognising an internationally entity.
      Aspects of professionalism, practice, regulation and registration can then be
      refined to produce a universally understood inclusive community without loss of
      distinction to sub-specialties within it. METHODS: The author utilised literature
      searches, research studies, domain knowledge and cooperative inquiries as
      context. Evaluation of issues is grounded in learned society investigations of
      professionalism and commitment to development of professional registration of
      those in informatics for the care domain. RESULTS: Transition from isolated
      applications through interfaced 'best of breed' solutions working together to
      integrated closely coupled single-vendor solutions is mirrored by professional
      groups, established through special interests, working together on big
      initiatives and then formally benefiting from a cohesive group. Phasing of such
      staged development is different by country or by focus/topic. CONCLUSIONS: The
      global HI situation will never again be as diverse as historically it was.
      Recognition of the lifecycle of the interacting factors explored in this paper
      will help HI to assume a world-wide brand identity whilst sustaining the
      subsidiarity of specialist cohorts within it.

PMID- 17019500
TI  - Medical informatics and bioinformatics: integration or evolution through
      scientific crises?
AB  - OBJECTIVES: To contribute a new perspective on recent investigations into the
      scientific foundations of medical informatics (MI) and bioinformatics (BI). To
      support efforts that could generate synergies and new research directions.
      METHODS: MI and BI are compared and contrasted from a philosophy of science
      perspective. Historical examples from MI and BI are analyzed based on contrasting
      viewpoints about the evolution of scientific disciplines. RESULTS: Our analysis
      suggests that the scientific approaches of MI and BI involve different
      assumptions and foundations, which, together with largely non-overlapping
      communities of researchers for the two disciplines, have led to different courses
      of development. We indicate how their respective application domains, medicine,
      and biology may have contributed to these differences in development.
      CONCLUSIONS: An analysis from the point of view of the philosophy of science is
      characteristic of established scientific disciplines. From a Kuhnian perspective,
      both disciplines may be entering a period of scientific crisis, where their
      foundations are questioned and where new ideas (or paradigm shifts) and a
      progressive research programme are needed to advance them scientifically. We
      discuss research directions and trends both supporting and challenging
      integration of the subdisciplines of MI and BI into a unified field of biomedical
      informatics (BMI), centered around the evolution of information cybernetics.

PMID- 17019501
TI  - Medical informatics in medical research - the Severe Malaria in African Children
      (SMAC) Network's experience.
AB  - OBJECTIVES: Computers are widely used for data management in clinical trials in
      the developed countries, unlike in developing countries. Dependable systems are
      vital for data management, and medical decision making in clinical research.
      Monitoring and evaluation of data management is critical. In this paper we
      describe database structures and procedures of systems used to implement,
      coordinate, and sustain data management in Africa. We outline major lessons,
      challenges and successes achieved, and recommendations to improve medical
      informatics application in biomedical research in sub-Saharan Africa. METHODS: A
      consortium of experienced research units at five sites in Africa in studying
      children with disease formed a new clinical trials network, Severe Malaria in
      African Children. In December 2000, the network introduced an observational study
      involving these hospital-based sites. After prototyping, relational database
      management systems were implemented for data entry and verification, data
      submission and quality assurance monitoring. RESULTS: Between 2000 and 2005,
      25,858 patients were enrolled. Failure to meet data submission deadline and data
      entry errors correlated positively (correlation coefficient, r = 0.82), with more
      errors occurring when data was submitted late. Data submission lateness
      correlated inversely with hospital admissions (r = -0.62). CONCLUSIONS:
      Developing and sustaining dependable DBMS, ongoing modifications to optimize data
      management is crucial for clinical studies. Monitoring and communication systems
      are vital in multi-center networks for good data management. Data timeliness is
      associated with data quality and hospital admissions.

PMID- 17019502
TI  - A closed queueing network approach to the analysis of patient flow in health care
      systems.
AB  - OBJECTIVES: To model patient flow in health care systems with bed capacity
      constraints in order to provide a useful decision aid for health service
      managers. METHODS: We model the patient flow of health care systems using a
      closed queueing network framework with the assumption that the system is always
      full. Key performance measures of the health care system are also derived.
      RESULTS: Using parameters taken from a study of a geriatric department in the UK,
      we show that the model is useful in helping service managers to gain better
      understanding of the behaviour of the system. In addition, we demonstrate that
      the model could help improving decision-making by allowing managers to explore
      different options and evaluate their impacts on performance. Our findings
      highlight the importance of policy makers taking into account the interactions
      between different phases of care. CONCLUSIONS: We have developed a novel approach
      to modelling the flow of patients through health care systems with constrained
      bed capacity.

PMID- 17019503
TI  - A global socio-economic-medico-legal model for the sustainability of longitudinal
      electronic health records - part 2.
AB  - OBJECTIVES: This paper pursues the challenge of sustaining lifetime electronic
      health records (EHRs) based on a comprehensive socio-economic-medico-legal model.
      The notion of a lifetime EHR extends the emerging concept of a longitudinal and
      cross-institutional EHR and is invaluable information for increasing patient
      safety and quality of care. METHODS: The challenge is how to compile and sustain
      a coherent EHR across the lifetime of an individual. Several existing and
      hypothetical models are described, analyzed and compared in an attempt to suggest
      a preferred approach. RESULTS: The vision is that lifetime EHRs should be
      sustained by new players in the healthcare arena, who will function as
      independent health record banks (IHRBs). Multiple competing IHRBs would be
      established and regulated following preemptive legislation. They should be
      neither owned by healthcare providers nor by health insurer/payers or government
      agencies. The new legislation should also stipulate that the records located in
      these banks be considered the medico-legal copies of an individual's records, and
      that healthcare providers no longer serve as the legal record keepers.
      CONCLUSIONS: The proposed model is not centered on any of the current players in
      the field; instead, it is focussed on the objective service of sustaining
      individual EHRs, much like financial banks maintain and manage financial assets.
      This revolutionary structure provides two main benefits: 1) Healthcare
      organizations will be able to cut the costs of long-term record keeping, and 2)
      healthcare providers will be able to provide better care based on the
      availability of a lifelong EHR of their new patients.

PMID- 17019504
TI  - Process potential screening - an instrument to improve business processes in
      hospitals.
AB  - OBJECTIVES: Hospitals are increasingly under pressure to optimize their
      processes. So far, an instrument to systematically identify the potentials for
      improvement of a given business process is missing. The aim of this project is to
      develop such an instrument. METHODS: Initially, central aspects of the quality of
      a hospital process were identified on the basis of a systematic literature
      review. Secondary to that, criteria to measure quality aspects were defined: More
      than 300 criteria from medical and business informatics, economics and quality
      management publications were gathered and systematically aggregated. RESULTS: As
      a result, the Process Potential Screening (PPS) instrument was developed. The PPS
      is a matrix containing two axes: Axis I comprises 30 quality aspects referring to
      results, execution and control of hospital processes. Axis II comprises 16
      quality criteria (e.g., customer satisfaction, time). The PPS displays
      approximately 400 relevant combinations of those quality aspects and quality
      criteria that help to identify potentials for improvement of a given hospital
      process. It utilizes different methods for the measurement of the criteria and
      for application by way of individuals or groups. CONCLUSIONS: In using the PPS,
      relevant potentials for improvement were identified in ten typical hospital
      processes. The instrument's practicability must now be examined in further
      studies by the final target group (e.g., quality or project managers, and the
      staff responsible for processes).

PMID- 17019505
TI  - Estimates of the number of cancer patients hospitalized in a geographic area
      using claims data without a unique personal identifier.
AB  - OBJECTIVE: In French national claims databases, claims are currently anonymous
      i.e. not linked to individual patients. In order to improve our estimate of the
      medical activity related to cancer in one French region, a statistical method was
      developed to use claims data to assess the number of cancer patients hospitalized
      in acute care. METHODS: This method used the medical and administrative
      information available in the claims (i.e. age, primary site, length of stay) to
      predict an average number of stays per patient, followed by a number of patients.
      It was based on a two-phase study design using an internal dataset which
      contained personal identifiers to estimate the model parameters. RESULTS: The
      predicted number of acute care patients hospitalized in one or several health
      care centers in one French region was 38,109 with a 95% predictive interval
      (37,990; 38,228) for the first six months of 2002. A prediction error of 24 per
      thousand was found. CONCLUSION: We provide a good estimate of the morbidity in
      acute care hospitals using claims data that is not linked to individual patients.
      This estimate reflects the medical activity and can be used to anticipate acute
      care needs.

PMID- 17019506
TI  - Characterizing Decision Support Telemedicine Systems.
AB  - OBJECTIVES: Decision Support Telemedicine Systems (DSTS) are at the intersection
      of two disciplines: tele-medicine and clinical decision support systems (CDSS).
      The objective of this paper is to provide a set of characterizing properties for
      DSTSs. This characterizing property set (CPS) can be used for typing, classifying
      and clustering DSTSs. METHODS: We performed a systematic keyword-based literature
      search to identify candidate-characterizing properties. We selected a subset of
      candidates and refined them by assessing their potential in order to obtain the
      CPS. RESULTS: The CPS consists of 14 properties, which can be used for the
      uniform description and typing of applications of DSTSs. The properties are
      grouped in three categories that we refer to as the problem dimension, process
      dimension, and system dimension. We provide CPS instantiations for three
      prototypical applications. CONCLUSIONS: The CPS includes important properties for
      typing DSTSs, focusing on aspects of communication for the telemedicine part and
      on aspects of decisionmaking for the CDSS part. The CPS provides users with tools
      for uniformly describing DSTSs.

PMID- 17019507
TI  - Modeling end-users' acceptance of a knowledge authoring tool.
AB  - OBJECTIVES: Knowledge bases comprise a vital component in the classic medical
      expert system model, yet the knowledge acquisition process by which they are
      created has been characterized as highly iterative and labor-intensive. The
      difficulty of this process underscores the importance of knowledge authoring
      tools that satisfy the demands of end-users. The authors hypothesize that the
      acceptability of a knowledge authoring tool for the creation of medical knowledge
      base content can be predicted by an accepted model in the information technology
      (IT) field, specifically the Technology Acceptance Model (TAM). METHODS: An
      online survey was conducted amongst knowledge base authors who had previously
      established experience with the authoring tool software. The Likert-based
      questions in the survey were patterned directly after accepted TAM constructs
      with minor modifications to particularize them to the software being used. The
      results were analyzed using structural equation modeling. RESULTS: The TAM
      performed well in predicting endusers' behavioral intentions to use the knowledge
      authoring tool. Five out of seven goodness-of-fit statistics indicate that the
      model represents the behavioral intentions of the authors well. All but one of
      the hypothesized relationships specified by the TAM were significant with p
      values less than 0.05. CONCLUSIONS: The TAM provides an adequate means by which
      development teams can anticipate and better understand what aspects of a
      knowledge authoring tool are most important to their target audience. Further
      research involving other behavioral models and an expanded user base will be
      necessary to better understand the scope of issues that factor into
      acceptability.

PMID- 17019508
TI  - Two models for outcome prediction - a comparison of logistic regression and
      neural networks.
AB  - OBJECTIVES: Accurately predicting disease progress from a set of predictive
      variables is an important aspect of clinical work. For binary outcomes, the
      classical approach is to develop prognostic logistic regression (LR) models.
      Alternatively, machine learning algorithms were proposed with artificial neural
      networks (ANN) having become popular over the last decades. Although some studies
      have compared predictive accuracies of LR and ANN models, some concerns regarding
      their methodological quality have been voiced. Our comparison has the advantage
      of being based on two large independent data sets allowing for elaborate model
      development and independent validation. METHODS: From the German Stroke Database,
      a learning data set including 1754 prospectively recruited patients with acute
      ischemic stroke was used. Utilizing LR and ANN, two prognostic models were
      developed predicting restitution of functional independence and survival after
      100 days. The resulting models were applied to classify 1470 patients with acute
      ischemic stroke; this test data set was collected independently from the learning
      data. Error fractions in the test data were determined, and differences in error
      fractions between the algorithms were calculated with 95% confidence intervals.
      RESULTS: For most prognostic models, error fractions in the test data were below
      40%. There was no difference between the algorithms except for the model
      predicting completely versus incompletely restituted or deceased patients
      (difference in error fractions = 4.01% [2.10-5.96%], p = 0.0001). CONCLUSIONS:
      The conscientiously applied LR remains the gold standard for prognostic
      modelling; however, ANN can be an alternative automated "quick and easy"
      multivariate analysis.

PMID- 17019509
TI  - Measuring agreement for ordered ratings in 3 x 3 tables.
AB  - OBJECTIVES: When two raters consider a qualitative variable ordered according to
      three categories, the qualitative agreement is commonly assessed with a
      symmetrically weighted kappa statistic. However, these statistics can present
      paradoxes, since they may be insensitive to variations of either complete
      agreements or disagreements. METHODS: Agreement may be summarized by the relative
      amounts of complete agreements, partial and maximal disagreements beyond chance.
      Fixing the marginal totals and the trace, we computed symmetrically weighted
      kappa statistics and we developed a new statistic for qualitative agreements.
      Data sets from the literature were used to illustrate the methods. RESULTS: We
      show that agreement may be better assessed with the unweighted kappa index,
      kappa(c), and a new statistic zeta, which assesses the excess of maximal
      disagreements with respect to the partial ones, and does not depend on a
      particular weighting system. When zeta is equal to zero, maximal and partial
      disagreements beyond chance are equal. With its estimated large sample variance,
      we compared the values of two contingency tables. CONCLUSIONS: The (kappa(c),
      zeta) pair is sensitive to variations in agreements and/or disagreements and
      enables locating the difference between two qualitative agreements. The
      qualitative agreement is better with increasing values of kappa(c) and zeta.

PMID- 17019510
TI  - Association between split selection instability and predictive error in survival
      trees.
AB  - OBJECTIVES: To evaluate split selection instability in six survival tree
      algorithms and its relationship with predictive error by means of a bootstrap
      study. METHODS: We study the following algorithms: logrank statistic with
      multivariate p-value adjustment without pruning (LR), Kaplan-Meier distance of
      survival curves (KM), martingale residuals (MR), Poisson regression for censored
      data (PR), within-node impurity (WI), and exponential log-likelihood loss (XL).
      With the exception of LR, initial trees are pruned by using split-complexity, and
      final trees are selected by means of cross-validation. We employ a real dataset
      from a clinical study of patients with gallbladder stones. The predictive error
      is evaluated using the integrated Brier score for censored data. The relationship
      between split selection instability and predictive error is evaluated by means of
      box-percentile plots, covariate and cutpoint selection entropy, and cutpoint
      selection coefficients of variation, respectively, in the root node. RESULTS: We
      found a positive association between covariate selection instability and
      predictive error in the root node. LR yields the lowest predictive error, while
      KM and MR yield the highest predictive error. CONCLUSIONS: The predictive error
      of survival trees is related to split selection instability. Based on the low
      predictive error of LR, we recommend the use of this algorithm for the
      construction of survival trees. Unpruned survival trees with multivariate p-value
      adjustment can perform equally well compared to pruned trees. The analysis of
      split selection instability can be used to communicate the results of tree-based
      analyses to clinicians and to support the application of survival trees.

PMID- 17019511
TI  - Deconfounding microarray analysis - independent measurements of cell type
      proportions used in a regression model to resolve tissue heterogeneity bias.
AB  - OBJECTIVES: Microarray analysis requires standardized specimens and evaluation
      procedures to achieve acceptable results. A major limitation of this method is
      caused by heterogeneity in the cellular composition of tissue specimens, which
      frequently confounds data analysis. We introduce a linear model to deconfound
      gene expression data from tissue heterogeneity for genes exclusively expressed by
      a single cell type. METHODS: Gene expression data are deconfounded from tissue
      heterogeneity effects by analyzing them using an appropriate linear regression
      model. In our illustrating data set tissue heterogeneity is being measured using
      flow cytometry. Gene expression data are determined in parallel by real time
      quantitative polymerase chain reaction (qPCR) and microarray analyses.
      Verification of deconfounding is enabled using protein quantification for the
      respective marker genes. RESULTS: For our illustrating dataset, quantification of
      cell type proportions for peripheral blood mononuclear cells (PBMC) from
      tuberculosis patients and controls revealed differences in B cell and monocyte
      proportions between both study groups, and thus heterogeneity for the tissue
      under investigation. Gene expression analyses reflected these differences in
      celltype distribution. Fitting an appropriate linear model allowed us to
      deconfound measured transcriptome levels from tissue heterogeneity effects. In
      the case of monocytes, additional differential expression on the single cell
      level could be proposed. Protein quantification verified these deconfounded
      results. CONCLUSIONS: Deconfounding of transcriptome analyses for cellular
      heterogeneity greatly improves interpretability, and hence the validity of
      transcriptome profiling results.

PMID- 17019512
TI  - Electrodynamic heart model construction and ECG simulation.
AB  - OBJECTIVES: In this paper, we present a unified electrodynamic heart model that
      permits simulations of the body surface potentials generated by the heart in
      motion. The inclusion of motion in the heart model significantly improves the
      accuracy of the simulated body surface potentials and therefore also the 12-lead
      ECG. METHODS: The key step is to construct an electromechanical heart model. The
      cardiac excitation propagation is simulated by an electrical heart model, and the
      resulting cardiac active forces are used to calculate the ventricular wall motion
      based on a mechanical model. The source-field point relative position changes
      during heart systole and diastole. These can be obtained, and then used to
      calculate body surface ECG based on the electrical heart-torso model. RESULTS: An
      electromechanical biventricular heart model is constructed and a standard 12-lead
      ECG is simulated. Compared with a simulated ECG based on the static electrical
      heart model, the simulated ECG based on the dynamic heart model is more accordant
      with a clinically recorded ECG, especially for the ST segment and T wave of a V1
      V6 lead ECG. For slight-degree myocardial ischemia ECG simulation, the ST segment
      and T wave changes can be observed from the simulated ECG based on a dynamic
      heart model, while the ST segment and T wave of simulated ECG based on a static
      heart model is almost unchanged when compared with a normal ECG. CONCLUSIONS:
      This study confirms the importance of the mechanical factor in the ECG
      simulation. The dynamic heart model could provide more accurate ECG simulation,
      especially for myocardial ischemia or infarction simulation, since the main ECG
      changes occur at the ST segment and T wave, which correspond with cardiac systole
      and diastole phases.

PMID- 17019513
TI  - The impact of rotary blood pump in conjunction with mechanical ventilation on
      ventricular energetic parameters - numerical simulation.
AB  - OBJECTIVES: Aim of this work is to study the impact of left ventricular rotary
      blood pump assistance, on energetic variables, when mechanical ventilation (MV)
      of the lungs is applied. METHODS: Computer simulation was used to perform this
      study. Lumped parameter models reproduce the circulatory system. Variable
      elastance models reproduce the Starling's law of the heart for each ventricle.
      After the reproduction of ischemic heart disease left ventricular assistance was
      applied using a model of rotary blood pump. The pump speed was changed in steps
      and was assumed to be constant during each step. The influence of mechanical
      ventilation was introduced by different values of positive mean thoracic
      pressure. RESULTS: The increase of the rotational speed has a significant
      influence on some ventricular energetic variables. In fact it decreased left
      ventricular external work, left and right ventricular pressure-volume area and
      the left ventricular efficiency. Finally, it increased the right ventricular
      efficiency but had no influence on the right ventricular external work. The
      increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of
      external work, pressure-volume area (right ventricular pressure-volume area
      dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while
      left ventricular efficiency remained almost stable. CONCLUSIONS: Numerical
      simulation is a very suitable tool to predict changes of not easily measurable
      parameters such as energetic ventricular variables when mechanical assistance of
      heart and/or lungs is applied independently or simultaneously.

PMID- 17019514
TI  - Induction of eryptosis by cyclosporine.
AB  - Side effects of cyclosporine treatment include anemia. Most recent studies have
      found that anemia may be caused by triggering of suicidal erythrocyte death
      (eryptosis), i.e. activation of an erythrocyte scramblase and phosphatidylserine
      exposure at the erythrocyte surface. Phosphatidylserine exposing cells are
      rapidly cleared from circulating blood by phagocytosis. Stimulators of
      erythrocyte membrane scrambling include cytosolic Ca(2+) and ceramide, which are
      increased by entry through Ca2+-permeable cation channels and by activation of a
      sphingomyelinase, respectively. The present study has been performed to test for
      an effect of cyclosporine on eryptosis. Erythrocytes from healthy volunteers were
      exposed to cyclosporine, and phosphatidylserine exposure (annexin V binding),
      cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3-dependent
      fluorescence), ceramide formation (anti-ceramide-FITC antibody), and 45Ca2+
      uptake were determined by flow cytometry and tracer flux measurements,
      respectively. Exposure of erythrocytes to cyclosporine triggered annexin V
      binding and significantly enhanced the increased annexin V binding both following
      glucose depletion and after hyperosmotic or isotonic cell shrinkage. However,
      cyclosporine significantly decreased cytosolic Ca2+ activity and did not
      stimulate 45Ca2+ uptake. Instead, cyclosporine transiently stimulated ceramide
      formation, decreased the cytosolic ATP concentration and potentiated the decline
      of cytosolic ATP concentration following glucose depletion. Elevated ceramide
      levels and ATP depletion, in turn, sensitize the erythrocytes for the eryptotic
      effects of Ca2+. The present observations may provide a mechanistic explanation
      for the anemia following treatment with this important immunosuppressive drug.

PMID- 17019516
TI  - Increased osteoprotegerin in Italian haemodialysis patients.

PMID- 17019515
TI  - Potential for bone turnover markers to cost-effectively identify and select post
      menopausal osteopenic women at high risk of fracture for bisphosphonate therapy.
AB  - INTRODUCTION AND HYPOTHESIS: Over half of all fractures among post-menopausal
      women occur in those who do not have osteoporosis by bone density criteria.
      Measurement of bone turnover may cost-effectively identify a subset of women with
      T-score >-2.5 for whom anti-resorptive drug therapy is cost-effective. METHODS:
      Using a Markov model, we estimated the cost per quality adjusted life year (QALY)
      for five years of oral bisphosphonate compared to no drug therapy for osteopenic
      post-menopausal women aged 60 to 80 years with a high (top quartile) or low
      (bottom 3 quartiles) level of a bone turnover marker. RESULTS: For women with
      high bone turnover, the cost per QALY gained with alendronate compared to no drug
      therapy among women aged 70 years with T-scores of -2.0 or -1.5 were $58,000 and
      $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also
      reduced the risk of non-vertebral fractures by 20% among osteopenic women with
      high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for
      women age 70 with high bone turnover and T-scores of -2.0 and -1.5, respectively.
      CONCLUSION: Measurement of bone turnover markers has the potential to identify a
      subset of post-menopausal women without osteoporosis by bone density criteria for
      whom bisphosphonate therapy to prevent fracture is cost-effective. The size of
      that subset highly depends on the assumed efficacy of bisphosphonates for
      fracture risk reduction among women with both a T-score >-2.5 and high bone
      turnover and the cost of bisphosphonate treatment.

PMID- 17019517
TI  - Low-carbohydrate, high-protein diets that restrict potassium-rich fruits and
      vegetables promote calciuria.

PMID- 17019518
TI  - The effect of socioeconomic status on bone density testing in a public health
      care system.
AB  - INTRODUCTION AND HYPOTHESIS: An inverse relationship exists between socio
      economic status (SES) and osteoporotic fractures. In publicly funded health-care
      systems there should be no barriers to accessing bone mineral density (BMD)
      testing, especially for those at increased fracture risk. Our hypothesis was that
      there would be a positive association between SES and BMD utilization (i.e.
      higher utilization rates in higher income women), resulting in disparities that
      disadvantage lower SES or lower income women. METHODS: A population-based BMD
      database from the Manitoba Bone Density Program was utilized to assess the
      association between SES (defined using income quintiles) and BMD utilization
      rates in women aged 50 years and older (n=107,944) for the 2001-2002 fiscal year.
      Analyses were stratified by age (50-64 years old and 65 years or older) and by a
      morbidity index obtained from the Johns Hopkins University Adjusted Clinical
      Group Case-Mix Adjustment System. RESULTS: Regression models demonstrated
      significantly higher BMD utilization rates among high SES women in all age and
      morbidity strata. Rate ratios varied from 1.76 (95% CI: 1.52-2.04) in 50- to 64
      year-old women to 2.36 (95% CI: 1.60-3.49) in low morbidity women aged 65 or
      older. CONCLUSION: Within the context of a publicly funded health-care system
      significant inverse associations are demonstrated between SES and BMD utilization
      rates. Further research is needed to better understand the nature of these
      associations and how they may contribute to health outcomes.

PMID- 17019519
TI  - Menstrual cycle lengths and bone mineral density: a cross-sectional, population
      based study in rural Chinese women ages 30-49 years.
AB  - INTRODUCTION: The menstrual cycle involves periodic fluctuations in estrogen and
      progesterone levels. Longer cycles have been associated with longer follicular
      phase, delayed estrogen peak and a lower mean oestradiol level of the entire
      cycle. METHODS: We hypothesized that prolonged menstrual cycle length is
      associated with decreased bone mineral density (BMD) in a population of pre- and
      perimenopausal women. This population-based cross-sectional study was conducted
      in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who
      did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed
      during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD
      measurements were taken at four skeletal sites: whole body, total hip, femoral
      neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short
      normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the
      prior year were assessed by questionnaire. RESULTS: Prolonged menstrual cycle was
      consistently associated with decreased BMD at whole body, total hip, and femoral
      neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged
      menstrual cycle was also associated with decreased lumbar spine BMD for women
      aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual
      cycle length in the previous year was inversely associated with whole-body BMD
      (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and
      femoral neck BMD relative to women with short normal cycles in the 30-39 age
      group; and had significantly lower whole body and total hip BMD relative to short
      normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ
      from BMD in women with short normal cycles at any of the skeletal sites.
      CONCLUSIONS: We conclude that prolonged menstrual cycle length is associated with
      decreased BMD in pre- and perimenopausal women in this population.

PMID- 17019520
TI  - Effects of a combined alendronate and calcitriol agent (Maxmarvil) on bone
      metabolism in Korean postmenopausal women: a multicenter, double-blind,
      randomized, placebo-controlled study.
AB  - INTRODUCTION: A randomized, double-blind, prospective, 24-week clinical trial was
      performed to evaluate the effects of a combinative agent, Maxmarvil, of
      calcitriol (0.5 mug) and alendronate (5 mg) on bone metabolism in postmenopausal
      women. METHODS: A total of 217 postmenopausal women with osteoporosis were
      enrolled; 199 patients were randomly assigned to one of two treatment groups
      (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D
      deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they
      received any drugs affecting bone metabolism before enrollment. Bone mineral
      densities (BMD) of L1-L4 and the femur were measured by dual-energy X-ray
      absorptiometry (DXA) at the initial assessment and after 6 months of treatment.
      Serum biochemical assays, including serum calcium, 24-h urinary calcium
      excretion, and bone turnover markers (both bone-specific alkaline phosphatase
      [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after
      3 and 6 months of treatment. RESULTS: In the Maxmarvil group, the BMD of the
      lumbar spine increased up to 2.42+/-0.5% from the baseline after 6 months
      (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was
      0.28+/-0.5% after 6 months. There was no significant difference in femoral BMD
      between the two groups. The levels of bsALP and NTx were significantly lower in
      the Maxmarvil group than in the alfacalcidol group (-22.04+/-3.9% vs. -11.42+/
      2.8% [p<0.05] and -25.46+/-5.2% vs. 1.24+/-6.2% [p<0.001], respectively).
      Interestingly, there was a significantly smaller amount of 24-h urinary calcium
      in the Maxmarvil group (p<0.05). CONCLUSIONS: Our study demonstrates that a
      combination of calcitriol and alendronate is quite effective in preventing bone
      loss, with the advantage of lesser hypercalciuric effect of calcitriol in the
      postmenopausal osteoporotic women.

PMID- 17019521
TI  - Disuse and orchidectomy have additional effects on bone loss in the aged male
      rat.
AB  - INTRODUCTION: A severely osteopenic rat model was obtained by combining
      orchidectomy (ORX) and disuse (due to local paralysis induced by botulinum toxin
      [BTX] in the quadriceps muscle). METHODS: Forty-two aged male rats (5-6 months
      old) were randomized into three groups: 18 were SHAM operated; 6 were ORX; and 18
      were ORX and BTX injected in the right hindlimb. One, two, and three months after
      surgery, bone mass (BV/TV) and microarchitectural parameters (Tb.Th, Tb.N, Tb.Sp,
      Tb.Pf, and structure model index [SMI]) were measured by microcomputed tomography
      (microCT) on the primary and secondary spongiosa of the femur. Osteoid parameters
      (OS/BS, O.Th), the number of osteoclasts (Nb.Oc), and the mineral apposition rate
      (Ct.MAR, Cn.MAR) were measured by histology. The serum tartrate-resistant acid
      phosphatase (TRAcP) 5b activity was measured by immunoassay. RESULTS: ORX induced
      a decrease of BV/TV, Tb.N and an increase of Tb.Sp, Tb.Pf, and SMI on both
      primary and secondary spongiosa. ORX and BTX had cumulative effects on bone loss,
      since differences were maximized on the right femur. The decrease in BV/TV
      reached -65%. Osteoid parameters and mineral apposition rate increased during the
      time course of the study. A peak of serum TRAcP was found at 7 days post-ORX.
      TRAcP levels reached the highest values in the ORX-BTX groups and the effect
      lasted longer than in the group with ORX alone. The association of ORX-BTX
      induced a greater bone resorption, due to the removal of complete trabeculae,
      compared to ORX alone. CONCLUSION: This model induced a severe and rapid bone
      loss and can be used to explore pharmacological- and biomaterial-based
      countermeasures.

PMID- 17019522
TI  - Skeletal benefits from calcium supplementation are limited in children with
      calcium intakes near 800 mg daily.
AB  - INTRODUCTION AND HYPOTHESIS: Calcium supplementation enhances bone mass accrual
      during administration, with a sustained benefit observed using milk-based calcium
      but not calcium salts. We tested the hypothesis that calcium from milk minerals
      but not calcium carbonate will be sustained after supplementation was
      discontinued. METHODS: Ninety-nine pre-pubertal boys and girls aged 5-11 years
      were followed for 12 months after being randomized to receive 800 mg/day of
      calcium from milk minerals (MM) or calcium carbonate (CC), or a placebo (Pla) in
      a 10-month double blind study. Total body and regional BMC, and femoral shaft
      bone dimensions were measured using dual energy x-ray absorptiometry. Group
      differences were determined using ANCOVA. RESULTS: In the intention to treat
      analysis of the entire sample, no group differences were observed in increments
      in BMC or bone dimensions during or after supplementation. In those children who
      remained pre-pubertal, greater gains in pelvis BMC in the milk mineral group than
      controls were sustained (37.9 versus 29.3% respectively, p<0.02). CONCLUSION: In
      healthy children consuming about 800 mg calcium daily, calcium supplementation
      with milk minerals or calcium carbonate does not appear to be produce
      biologically meaningful benefits to skeletal health. A benefit of calcium
      supplementation in pre-pubertal was evident, but inconclusive, with the
      biological significance of the effect of calcium supplementation at the pelvis,
      and the longevity of this effect to be determined.

PMID- 17019523
TI  - The prevalence of significant left-right differences in hip bone mineral density.
AB  - INTRODUCTION: We determined the prevalence of left-right differences in hip bone
      mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and the resultant
      consequence, namely: the frequency at which patients would be classified
      differently if lumbar spine and only one hip (rather than both hips) were
      measured. METHODS: This was a retrospective DXA scan reanalysis of 3012 white
      women >or=50 yrs who had scans of both hips using Hologic DXA systems. The
      difference between left and right hips was considered significant if it exceeded
      the least significant change (LSC) for any of three hip subregions (total hip,
      femoral neck, trochanter). The number of women with osteoporosis in both hips,
      the left hip only, or the right hip only was determined by lowest T-score from
      total hip, femoral neck, or trochanter. RESULTS: Despite high left-right
      correlations of subregion BMD, significant left-right differences in BMD were
      common: the difference exceeded the LSC for 47% of women at total hip, 31% at
      femoral neck, and 56% at trochanter. Left-right differences in BMD that exceeded
      the LSC affected the percent agreement of left-right hip classification: for all
      women irrespective of spine status, there was 77% classification (diagnostic)
      agreement in hip pairs in which the left-right hip BMD difference exceeded the
      LSC versus 87% agreement in which LSC was not exceeded (significant difference in
      proportions, P<0.0001). The greatest risk of different classification would occur
      in women with normal spines as the diagnosis might be determined by hip T-scores.
      Using L1-4 lumbar spine T-scores, 1229 women were normal at the spine. Twenty
      four (2%) were osteoporotic at both hips. However, 12 women (1%) were
      osteoporotic only in the left hip (significantly different from zero, P<0.001)
      and 11 (1%) only in the right hip (P<0.001); of these 23 women, the difference in
      BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 16
      (70% of those with osteoporosis in only one hip). Using L1-4 lumbar spine T
      scores, 1159 women were osteopenic at the spine. Of these, 126 (11%) were
      osteoporotic at both hips, 54 (5%) only in the left hip (P<0.001), and 42 (4%)
      only in the right hip (P<0.001); of these 96 women, the difference in BMD between
      the osteoporotic hip and the contralateral hip exceeded the LSC in 56 (58% of
      those with osteoporosis in only one hip). CONCLUSIONS: A statistically
      significant number of women with osteoporosis are potentially classified
      differently when scanning only one hip as a result of the high prevalence of left
      right differences in BMD. Although the percentages are low, the total number of
      women affected may be large. From a public health perspective, the practice of
      scanning both hips could potentially identify more women with osteoporosis and
      may help prevent future hip fractures.

PMID- 17019524
TI  - Possible association of actin filaments with chloroplasts of spinach mesophyll
      cells in vivo and in vitro.
AB  - In palisade mesophyll cells of spinach (Spinacia oleracea L.) kept under low
      intensity white light, chloroplasts were apparently immobile and seemed to be
      surrounded by fine bundles of actin filaments. High-intensity blue light induced
      actin-dependent chloroplast movement concomitant with the appearance of a couple
      of long, straight bundles of actin filaments in each cell, whereas high-intensity
      red light was essentially ineffective in inducing these responses. The actin
      organization observed under low-intensity white light has been postulated to
      function in anchoring chloroplasts at proper intracellular positions through
      direct interaction with the chloroplasts. Intact chloroplasts, which retained
      their outer envelopes, were isolated after homogenization of leaves and Percoll
      centrifugation. No endogenous actin was detected by immunoblotting in the final
      intact-chloroplast fraction prepared from the leaves kept under low-intensity
      white light or in darkness. In cosedimentation assays with exogenously added
      skeletal muscle filamentous actin, however, actin was detected in the intact
      chloroplast fraction precipitated after low-speed centrifugation. The association
      of actin with chloroplasts was apparently dependent on incubation time and
      chloroplast density. After partial disruption of the outer envelope of isolated
      chloroplasts by treatment with trypsin, actin was no longer coprecipitated. The
      results suggest that chloroplasts in spinach leaves can directly interact with
      actin, and that this interaction may be involved in the regulation of
      intracellular positioning of chloroplasts.

PMID- 17019525
TI  - Comparative study of cellular structures implicated in gravisensing in statocytes
      of primary and lateral roots of Vigna angularis.
AB  - The cellular structures of statocytes implicated in gravisensing in primary and
      lateral roots of Vigna angularis were compared. The statocytes of lateral roots
      already had small amyloplasts immediately after they emerged from the primary
      root. Although these amyloplasts sedimented, the lateral roots showed much weaker
      gravitropism than primary roots, at least until they reached a length of about 30
      mm. The nuclei were usually positioned in the upper end of the statocytes in both
      types of roots. Electron microscopic surveys showed that many tubular elements of
      endoplasmic reticulum (ER) were frequently localized in the lower end of the
      statocyte and they sometimes diverged or curved, suggesting that the ER forms a
      large reticulate complex. It is worth noting that statocytes with a large ER
      complex were found much more frequently in primary roots than in lateral roots.
      The amyloplasts were not always settled on this complex but were very frequently
      under it, especially in the primary roots. In lateral roots, they were usually
      localized under the ER complex when they were present. Thus, it is suggested that
      the differential development and organization of the amyloplast-ER complex system
      is involved in the differential gravitropism of the two types of roots.

PMID- 17019526
TI  - The cytoskeleton in the unique cell reproduction by conidiogenesis of the long
      neck yeast Fellomyces (Sterigmatomyces) fuzhouensis.
AB  - The morphology of conidiogenesis and associated changes in microtubules, actin
      distribution and ultrastructure were studied in the basidiomycetous yeast
      Fellomyces fuzhouensis by phase-contrast, fluorescence, and electron microscopy.
      The interphase cell showed a central nucleus with randomly distributed bundles of
      microtubules and actin, and actin patches in the cortex. The conidiogenous mother
      cell developed a slender projection, or stalk, that contained cytoplasmic
      microtubules and actin cables stretched parallel to the longitudinal axis and
      actin patches accumulated in the tip. The conidium was produced on this stalk. It
      contained dispersed cytoplasmic microtubules, actin cables, and patches
      concentrated in the cortex. Before mitosis, the nucleus migrated through the
      stalk into the conidium and cytoplasmic microtubules were replaced by a spindle.
      Mitosis started in the conidium, and one daughter nucleus then returned to the
      mother via an eccentrically elongated spindle. The cytoplasmic microtubules
      reappeared after mitosis. A strong fluorescence indicating accumulated actin
      appeared at the base of the conidium, where the cytoplasm cleaved eccentrically.
      Actin patches then moved from the stalk together with the retracting cytoplasm to
      the mother and conidium. No septum was detected in the long neck by electron
      microscopy, only a small amount of fine "wall material" between the conidium and
      mother cell. Both cells developed a new wall layer, separating them from the
      empty neck. The mature conidium disconnected from the empty neck at the end
      break, which remained on the mother as a tubular outgrowth. Asexual reproduction
      by conidiogenesis in the long-neck yeast F. fuzhouensis has unique features
      distinguishing it from known asexual forms of reproduction in the budding and
      fission yeasts. Fellomyces fuzhouensis develops a unique long and narrow neck
      during conidiogenesis, through which the nucleus must migrate into the conidium
      for eccentric mitosis. This is followed by eccentric cytokinesis. We found
      neither an actin cytokinetic ring nor a septum in the long neck, from which
      cytoplasm retracted back to mother cell after cytokinesis. Both the conidium and
      mother were separated from the empty neck by the development of a new lateral
      wall (initiated as a wall plug). The cytoskeleton is clearly involved in all
      these processes.

PMID- 17019527
TI  - Localization of an arabinogalactan protein epitope and the effects of Yariv
      phenylglycoside during zygotic embryo development of Arabidopsis thaliana.
AB  - Arabinogalactan proteins (AGPs) are a class of highly glycosylated proteins
      widely distributed in higher plants and thought to be involved in plant growth
      and development. In the present paper, Western blotting with the monoclonal
      antibodies JIM4, JIM13, and LM2 showed that JIM13 reacted best with total protein
      extracts from flowers and siliques of Arabidopsis thaliana. This monoclonal
      antibody was therefore used as a probe to localize the AGP epitope in zygotic
      embryos at different developmental stages. Immunofluorescent labeling with JIM13
      showed that AGPs were mainly distributed in the embryo proper and the top 1 to 2
      cells and basal part of suspensors. The results of immunogold labeling confirmed
      the JIM13 epitope distribution in the different cells of the suspensor. AGP
      immunofluorescence was also observed at the shoot apex meristem during transition
      from the globular to the heart embryo stage, but this gradually disappeared after
      the torpedo stage. After (beta-D-Glc)(3) Yariv phenylglycoside (betaGlcY), a
      synthetic reagent that specifically binds to AGPs, was added to A. thaliana ovule
      culture medium, the survival rate and frequency of development of ovules at the
      zygote stage decreased in a concentration-dependent manner, with complete
      inhibition at 100 microM. The frequency of embryo differentiation from the
      globular stage to heart or later stages also decreased sharply. When betaGlcY was
      removed 24 h after inoculation, the inhibitory effects were reversible in a
      concentration-dependent and time-dependent manner. The results show that betaGlcY
      can inhibit embryo development and differentiation in A. thaliana, and the
      inhibitory effects are concentration dependent and reversible, indicating that
      AGPs are involved in embryo differentiation and shoot meristem formation. The
      possible roles of AGPs in A. thaliana zygotic embryo development are also
      discussed.

PMID- 17019528
TI  - Molecular cloning and gene expression of a fibrillarin homolog of tobacco BY-2
      cells.
AB  - Fibrillarin is known to play an important role in precursor ribosomal RNA
      processing and ribosome assembly. The present study describes a fibrillarin
      homolog gene isolated from tobacco BY-2 cells and its expression during the cell
      cycle. The cDNA for a fibrillarin homolog, named NtFib1, was first cloned in
      Nicotiana tabacum with degenerate primers. It encodes 314 amino acids and the
      deduced amino acid sequence has some highly conserved functional domains, such as
      the glycine and arginine-rich (GAR) domain for nucleolar localization and the RNA
      binding motif. The C-terminal region is highly conserved and has 7 beta-sheets
      and 7 alpha-helices which are peculiar to fibrillarin. Thus, it is suggested that
      the fibrillarin homolog of this plant species functions in the same way as the
      fibrillarin already known from human and yeast cells. Northern blot analysis of
      BY-2 cells synchronized with aphidicolin or a combination of aphidicolin and
      propyzamide showed that the histone H4 gene was specifically expressed in the S
      phase but NtFib1 mRNA remained at high levels during the cell cycle. Examination
      of the localization of NtFib1 protein tagged with green-fluorescent protein (GFP)
      suggested that some persisting in the mitotic apparatus was eventually
      incorporated into reconstructed nucleoli in late telophase. Newly synthesized GFP
      tagged NtFib1 protein in the cytoplasm was added to the recycled protein in early
      mitosis. Highly concentrated actinomycin D completely inhibited the transcription
      of genes coding for rRNA (rDNA) but did not significantly suppress the amount of
      either NtFib1 mRNA or protein, although the NtFib1 protein was reversibly
      dislocated from nucleoli. Although hypoxic shock completely prohibited rDNA
      transcription, NtFib1 mRNA remained at the same level as in the control
      experiment, even after the 4 h treatment. These results indicate that the
      transcription of NtFib1 mRNA is not related to rDNA transcription and NtFib1 mRNA
      is resistant to disrupting factors during the cell cycle.

PMID- 17019530
TI  - Post-translational regulation of rotavirus protein NSP1 expression in mammalian
      cells.
AB  - The nonstructural rotavirus protein NSP1 binds specifically to viral mRNAs and to
      interferon regulatory factor 3 (IRF3), inducing IRF3 degradation through a
      proteasome-dependent pathway. By using a vaccinia virus expression system in
      mammalian cells, we found that the yield of NSP1 was 8- and 13-fold lower than
      the viral proteins VP2 or NSP3, respectively; while in the presence of proteasome
      inhibitors such difference could be reduced to 2- to 2.5-fold, respectively. The
      susceptibility of NSP1 to proteasome degradation was fully reversed in a dose
      dependent manner by transfection with the full complement of 11 molecules of
      translation-competent rotavirus mRNAs, but this effect was abrogated by the
      protein synthesis inhibitor cycloheximide. These results demonstrate that NSP1 is
      degraded through a proteasome-dependent pathway, and viral proteins, alone or in
      combination with viral mRNAs, interfere with such degradation.

PMID- 17019529
TI  - Verticillium dahliae toxin induced alterations of cytoskeletons and nucleoli in
      Arabidopsis thaliana suspension cells.
AB  - In plant cells, cytoskeletons play important roles in response to biotic and
      abiotic stresses. However, little is known about the dynamics of cytoskeletons
      when cells are attacked by unphysical stress factors such as elicitors and
      toxins. We report here that the toxin of Verticillium dahliae (VD toxin) induced
      changes of microfilaments (MFs) and microtubules (MTs) in Arabidopsis thaliana
      suspension-cultured cells. When cells were treated with a low concentration of VD
      toxin, MFs were disrupted ordinally from the cortex to the perinuclear region,
      and then recovered spontaneously; but the MTs persisted. The MFs in the
      perinuclear region showed more resistance to VD toxin than the cortical ones. In
      contrast, when cells were treated with a high concentration of VD toxin, MFs and
      MTs were disrupted sooner and more severely and did not recover spontaneously.
      Treatments with high concentrations of VD toxin also induced changes of nucleoli.
      At the early stages of treatment, a nucleus had a single ring-shaped nucleolus.
      At the later stages, multiple smaller and more brightly fluorescing nucleoli
      emerged in a single nucleus. Disrupted MFs could be recovered by removing the VD
      toxin before the ring-shaped nucleoli appeared. All these results showed that MFs
      and MTs play important roles in the early defense responses against VD toxin in
      Arabidopsis suspension cells. The cytoskeletons may be used as sensors and
      effectors monitoring the defense reactions. The changes of nucleoli induced by VD
      toxin should be important characteristics of cell death.

PMID- 17019531
TI  - Transient and stable expression of the HCV envelope glycoproteins in cell lines
      and primary hepatocytes transduced with a recombinant baculovirus.
AB  - A recombinant baculovirus, RecBV-E, encoding the hepatitis C virus (HCV) envelope
      proteins, E1 and E2, controlled by the cytomegalovirus promoter was constructed.
      RecBVs can infect mammalian cells, but fail to express proteins or replicate
      because the viral DNA promoters are not recognised. The RecBV-E transduced 86% of
      Huh7 cells and 22% of primary marmoset hepatocytes compared with 35% and 0.4%,
      respectively, after DNA transfection. Several stable cell lines were generated
      that constitutively expressed E1/E2 in every cell. No evidence of E1/E2-related
      apoptosis was noted, and the doubling times of cells were similar to that of the
      parental cells. A proportion of the E1/E2 was expressed on the surface of the
      stable cells as determined by flow cytometry and was detected by a conformation
      dependent monoclonal antibody. It is likely that the continued expression of
      E1/E2 in the stable cells resulted from integration of the RecBV DNA. Infection
      of Huh7 cells, in the absence of G418 selection, failed to result in expression
      of the foreign gene (in this case, eGFP) beyond 14-18 days. RecBVs that express
      HCV genes from a CMV promoter represent an effective means by which to transduce
      primary hepatocytes for expression and replication studies.

PMID- 17019532
TI  - A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in
      elderly patients with glioblastoma.
AB  - There is no standard of care for elderly patients (age>or=70 years) with newly
      diagnosed glioblastoma (GBM). In 15 consecutive patients (median age 79 years)
      treated with temozolomide (TMZ) (42 days on; 14 days off), median survival was 6
      months (range 4-14 months). This pilot study suggests that low dose daily TMZ may
      represent an alternative and equally effective treatment to more traditionally
      administered radiotherapy.

PMID- 17019533
TI  - Frequent loss of heterozygosity encompassing the hMLH1 locus in low grade
      astrocytic tumors.
AB  - The mismatch repair genes, hMLH1 (3p22) and hMSH2 (2p21), are commonly associated
      with accumulation of mutations and microsatellite instability. However, the
      status of their gene loci itself is often not addressed. In astrocytic tumors,
      the heterozygosity status of these genes with reference to tumor grade has not
      yet been determined. We have analyzed the heterozygosity status and locus
      specific instability in 43 glial tumors comprising 22 low grades diffuses
      astrocytoma (WHO Grade II, DA) and 21 glioblastoma multiforme (Grade IV GBM)
      using 10 microsatellite markers at 2p and 3p to elucidate the involvement of
      these loci in astrocytic tumorigenesis. We observed a significantly higher loss
      of heterozygosity (LOH) in 3p markers encompassing the hMLH1 gene locus in DA
      when compared to GBM (P = 0.008). In DA, while the frequency of LOH was observed
      to be higher in markers close to the hMLH1 gene ( approximately 40%), locus
      specific microsatellite instability (LSI) was higher ( approximately 30%) in
      markers localizing further to the gene. The frequency of LOH at markers on 2p,
      near the hMSH2 gene was, however, similar in DA and GBM (P = 0.451). Our results
      suggest that in the astrocytic tumorigenesis, LOH at the hMLH1 gene locus is an
      early event in tumorigenesis. However, the mismatch repair protein expression may
      be regulated by other cellular factors.

PMID- 17019534
TI  - Myocardial infarction in a young female with reninoma induced hypertension and
      myocardial bridging.
AB  - We present a case of myocardial infarction in a young female with reninoma
      induced hypertension and myocardial bridging. Reninoma is a rare and curable
      cause of secondary hypertension. Currently developed multi-detector computed
      tomography (MDCT) has permitted better evaluation of myocardial infarction and
      myocardial bridging. Myocardial infarction associated with reninoma and
      myocardial bridging has not been reported, and we report this interesting case.

PMID- 17019535
TI  - Surgical correction of mitral valve prolapse : a cure for recurrent ventricular
      tachycardia in Marfan syndrome?
AB  - We describe the case of a 3-year-old child with neonatal Marfan syndrome
      complicated by mitral valve prolapse with regurgitation, marked aortic root
      dilatation, and ventricular tachycardia. The patient had resolution of
      ventricular tachycardia following surgical intervention consisting of a valve
      sparing aortic root replacement and mitral valve annuloplasty.

PMID- 17019536
TI  - Evaluating the environmental performance of urban parks in Mediterranean cities:
      an example from the Barcelona metropolitan region.
AB  - In a context of increasing urban sprawl and water scarcity common to other
      Mediterranean cities, this article focuses on the urban parks in the Region of
      Barcelona (Catalonia, Spain) to examine how these parks are distributed in this
      region and to assess whether their design and management follow criteria adapted
      to Mediterranean environmental conditions, especially in what concerns water use.
      In order to evaluate the environmental performance of these parks, we selected
      four factors possibly influencing the adoption of park management practices at
      the local scale: urban density, population size of the municipality, municipal
      income per capita, and political orientation of the city council. After
      determining the location and area of urban parks in the region, we correlated
      these four explanatory factors with several management tasks extracted from two
      different samples of parks (one of 315 parks and another of 125 parks) and a
      survey of 86 city councils. Results show that, in general, urban parks were more
      frequent in large, dense, and left/green municipalities but that environmentally
      sound practices were more common in small and low-density municipalities. We
      conclude that changes in certain practices (especially the substitution of high
      water demanding species) could improve significantly the environmental
      performance of public spaces in large urban areas with Mediterranean climates.
      Our observations may be pertinent for other cities interested in the provision of
      environmental public goods such as parks that necessitate water for irrigation.

PMID- 17019537
TI  - Therapeutic effectiveness of a single vs multiple doses of erythropoietin after
      experimental myocardial infarction in rats.
AB  - BACKGROUND: Systemic application of recombinant human erythropoietin (rhEPO)
      greatly limits cardiac tissue damage and attenuates left ventricular (LV)
      remodeling after experimentally induced myocardial infarction (MI). However,
      multiple injections of rhEPO stimulate red blood cell production and elevate the
      hematocrit (Htc), which might negatively affect the outcome of acute MI. We
      compared the outcome of experimental MI in rats treated with a single or multiple
      doses of rhEPO. MATERIALS AND METHODS: Sprague-Dawley male rats were subjected to
      a permanent ligation of the left descending coronary artery (CL) or sham
      operation. Immediately after CL animals received either a single i.v. injection
      of 3,000 IU/kg of rhEPO, or a single injection plus additional injections of the
      same dose of rhEPO repeated daily for six more days. Echocardiography and blood
      collection for measurement of Htc were performed prior to, and at 2 and 4 weeks
      after CL; MI size was measured histologically 4 weeks after CL. RESULTS: A single
      injection of rhEPO elevated Htc by 11% (p < 0.05) 1 week after CL, but after
      multiple rhEPO injections Htc increased by 40%. In untreated rats a 140 and 340%
      expansion in end-diastolic and end-systolic LV volumes, respectively, and 55%
      decline in ejection fraction (EF) occurred during the 4 week period following CL.
      A single rhEPO dose attenuated the LV remodeling and EF reduction by 50%.
      Repeated rhEPO injections did not elicit any additional benefits in respect to LV
      remodeling. Moreover, at the end of 4 weeks, MI size was significantly reduced
      (by 40%) by a single injection, while after repeated rhEPO injections the
      reduction of MI size was not statistically significant. CONCLUSION: The results
      of this study indicate that multiple dosing of rhEPO after induced myocardial
      infarction in rats has no added therapeutic benefits over those achieved by a
      single dose.

PMID- 17019538
TI  - Healing unhealthy Hungarian hearts--at what cost?--With what benefit?

PMID- 17019539
TI  - Does gas exchange response to prone position predict mortality in hypoxemic acute
      respiratory failure?
AB  - OBJECTIVE: To determine whether gas exchange response to a first prone position
      session can predict patient outcome in hypoxemic acute respiratory failure.
      METHODS: Data from a previous multicenter randomized controlled trial were
      retrospectively analyzed for relationship between PaO(2)/FIO(2) ratio and PaCO(2)
      changes during the first 8-h prone position session to day 28 mortality rate; 370
      prone position sessions were analyzed. Arterial blood gas was measured in supine
      position before proning and in prone position at the end of the session. Gas
      exchange improvement was defined as increase in the PaO(2)/FIO(2) ratio of more
      than 20% (PaO(2)R) or decrease in PaCO(2) of more than 1 mmHg (PaCO(2)R). MAIN
      RESULTS: The 28-day mortality rate was 26.5% in PaO(2)R-PaCO(2)R, 31.7% in
      PaO(2)R-PaCO(2)NR, 38.9% in PaO(2)NR-PaCO(2)R, and 43% in PaO(2)NR-PaCO(2)NR (log
      rank 14.02, p = 0.003). In a Cox proportional hazards model the gas exchange
      response was a significant predictor to patient outcome with a 82.5% increase in
      risk of death in the case of PaO(2)NR-PaCO(2)R or PaO(2)NR-PaCO(2)NR, relative to
      the gas exchange improvement response (odds ratio 1.825). However, after
      adjusting for the difference in oxygenation between day 2 and day 1 the gas
      exchange response does no longer reach significance. CONCLUSION: In patients with
      hypoxemic acute respiratory failure initial improvement in gas exchange in the
      first PP session was associated with a better outcome, but this association
      disappeared when the change in oxygenation from day 1 to day 2 was taken into
      account, suggesting that underlying illness was the most important predictor of
      mortality in this patient population.

PMID- 17019540
TI  - Variability of cortisol assays can confound the diagnosis of adrenal
      insufficiency in the critically ill population.
AB  - OBJECTIVE: To compare the total plasma cortisol values obtained from three widely
      used immunoassays and a high pressure liquid chromatography (HPLC) technique on
      samples obtained from patients with sepsis. DESIGN AND SETTING: Observational
      interventional in the general intensive care unit of a metropolitan hospital
      PATIENTS AND PARTICIPANTS: Patients admitted to the intensive care unit with a
      diagnosis of sepsis and fulfilling criteria of systemic inflammatory response
      syndrome. INTERVENTIONS: Standard short synacthen test performed with 250microg
      cosyntropin. MEASUREMENTS AND RESULTS: Two of the three immunoassays returned
      results significantly higher than those obtained by HPLC: Immulite by 95% (95%CI
      31-188%) and TDx by 79% (21-165%). The limits of agreement for all three
      immunoassays with HPLC ranged from -62% to 770%. In addition, by classifying the
      patients into responders and non-responders to ACTH by standard criteria there
      was concordance in all assays in only 44% of patients. CONCLUSIONS: Immunoassay
      estimation of total plasma cortisol in septic patients shows wide assay related
      variation that may have significant impact in the diagnosis of relative adrenal
      insufficiency.

PMID- 17019541
TI  - The catheter site influences in the micro-organism responsible of arterial
      catheter-related infection.

PMID- 17019542
TI  - The European Directive 2001/20 for clinical research: friend or foe?

PMID- 17019543
TI  - A change in the Dutch Directive on Medical Research Involving Human Subjects
      strongly increases the number of eligible intensive care patients: an
      observational study.
AB  - OBJECTIVES: To determine the effect of a change in the "Dutch Directive on
      Medical Research Involving Human Subjects" (DD) on the number of eligible
      intensive care unit (ICU) patients for medical research. In addition, we
      determined how family members experience their role as acting representative for
      giving informed consent, and in turn whether patients feel their representatives
      would do well representing them. DESIGN AND SETTING: Prospective observational
      study in three Dutch ICUs. PARTICIPANTS: 714 consecutive ICU patients. Analysis
      was restricted to 211 patients who were incapacitated for more than 24h after ICU
      admission. MEASUREMENTS AND RESULTS: The old DD left 45.5% of patients without a
      legal representative; with the new DD this figure declines to 8.1%. Older age was
      significantly associated with the impossibility of obtaining informed consent in
      the old DD; after the change there was no effect of age. The median grade of
      confidence that representatives had in giving informed consent for incapacitated
      patients was 8.0 (IQR 7.0-9.0) on a scale from 0 to 10. Patients gave an equal
      median grade to their representatives. CONCLUSION: When patients' adult children
      are not legally allowed to give informed consent, older patients are excluded
      from medical research, causing selection bias. The change in the DD has increased
      the number of surrogates allowed to give informed consent. Representatives felt
      very confident in their ability to represent the patients. In turn patients were
      equally confident that their representatives were able to represent them.

PMID- 17019544
TI  - The hidden pulmonary dysfunction in acute lung injury.

PMID- 17019545
TI  - Effect of inspired oxygen fraction on alveolar derecruitment in acute respiratory
      distress syndrome.
AB  - OBJECTIVE: High fractions of inspired oxygen (FIO(2)) used in acute lung injury
      (ALI) may promote resorption atelectasis. The impact of derecruitment related to
      high FIO(2) in ALI is debated. We evaluated derecruitment with 100% vs. 60%
      FIO(2) at two levels of positive end-expiratory pressure (PEEP). PATIENTS:
      Fourteen consecutive patients with ALI were studied. INTERVENTIONS: Recruited
      volume at two PEEP levels was computed from two pressure-volume curves, recorded
      from PEEP and from zero end-expiratory pressure, using the sinusoidal flow
      modulation method. PEEP-induced recruitment was measured during prolonged
      expiration as the difference between the two curves at a given pressure.
      PaO(2)/FIO(2) was also measured. PEEP was 5 +/- 1 or 14 +/- 3 cmH(2)O and FIO(2)
      was 60% or 100%, yielding four combinations. We looked for differences between
      the beginning and end of a 30-min period with each combination. MEASUREMENT AND
      RESULTS: With low PEEP and 100% FIO(2), recruited volume decreased significantly
      from 68 +/- 53 to 39 +/- 43 ml and PaO(2)/FIO(2) from 196 +/- 104 to 153 +/- 83
      mmHg. With the three other combinations (low PEEP and 60% FIO(2) or high PEEP and
      60% or 100% FIO(2)) none of the parameters decreased significantly. CONCLUSION:
      In mechanically ventilated patients with ALI the breathing of pure oxygen leads
      to derecruitment, which is prevented by high PEEP.

PMID- 17019546
TI  - Refractory elevated intracranial pressure: intensivist's role in solving the
      dilemma of decompressive craniectomy.

PMID- 17019547
TI  - Investigating the effectiveness of critical care outreach services: a systematic
      review.
AB  - OBJECTIVE: We explored the impact of critical care outreach activity on patient
      and service outcomes and aimed to contribute to developing a typology of critical
      care outreach services. DESIGN: Following a sample search of Medline 15 relevant
      electronic databases were systematically searched from 1996 to 2004. Searches for
      publications from nine key authors and citations of eight key articles were
      performed. Hand searches of journals, bibliographies of reports and review
      articles, and conference abstracts were conducted. Relevant experts were
      contacted. A further two studies published after the review date were also
      included. Two reviewers assessed studies for inclusion, conducted quality
      assessment and extracted data. Data were synthesised using narrative techniques.
      MEASUREMENTS AND RESULTS: Seventeen papers and six brief reports were selected
      for inclusion from a list of 1,760 titles. As anticipated with a relatively new
      service such as critical care outreach, there were few controlled trials. There
      were two randomised controlled trials, 16 uncontrolled before and after studies,
      three quasi-experimental studies, one controlled before and after study and one
      post-only controlled study. The most frequent outcomes measured were mortality,
      cardiac arrest, unplanned critical care admissions from wards, length of stay,
      and critical care readmission rates. CONCLUSIONS: Although improvements in
      patient outcomes were found, the evidence in this review is insufficient to
      demonstrate this conclusively. The many differences in service delivery do not
      permit identification of service typology. Our findings point to a need for more
      comprehensive research of this expanding service in the United Kingdom.

PMID- 17019548
TI  - Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized
      clinical trial.
AB  - OBJECTIVE: To compare the effects of arginine-vasopressin (AVP) and
      norepinephrine (NE) on hemodynamic variables, organ dysfunction, and adverse
      events in early hyperdynamic septic shock. DESIGN AND SETTING: Randomized,
      controlled, open-label trial. PATIENTS AND PARTICIPANTS: Twenty-three patients
      with early (12h) hyperdynamic septic shock in two teaching hospitals.
      INTERVENTIONS: AVP (0.04-0.20 Umin(-1), n=13) as a single agent or NE (0.1
      2.8microg kg(-1)min(-1), n=10) infusion for 48[Symbol: see text]h to achieve mean
      arterial pressure at or above 70mmHg. MEASUREMENTS AND RESULTS: Hemodynamic
      parameters and Sequential Organ Failure Assessment (SOFA) score were measured.
      AVP and NE equally increased mean arterial pressure over 48h, but NE was required
      in 36% of AVP patients at 48h. Compared to baseline, AVP increased systemic
      vascular resistance, decreased exposure to NE, decreased cardiac output by
      decreasing heart rate, increased creatinine clearance, and improved SOFA score.
      The PrCO(2) - PaCO(2) difference remained stable throughout the study. One AVP
      patient developed acute coronary syndrome with dose-dependent ECG changes. Three
      patients in both groups died during their ICU stay. CONCLUSION: In early
      hyperdynamic septic shock, the administration of high-dose AVP as a single agent
      fails to increase mean arterial pressure in the first hour but maintains it above
      70mmHg in two-thirds of patients at 48h. AVP decreases NE exposure, has no effect
      on the PrCO(2) - PaCO(2 )difference, and improves renal function and SOFA score.

PMID- 17019549
TI  - Transfusion of erythrocyte concentrates produces a variable increment on cerebral
      oxygenation in patients with severe traumatic brain injury: a preliminary study.
AB  - OBJECTIVE: To investigate the long-term influence of erythrocyte transfusion on
      cerebral oxygenation in patients with severe traumatic brain injury. DESIGN:
      Prospective and observational study. SETTING: Neurotrauma intensive care unit of
      trauma center level I. PATIENTS: Sixty consecutive, hemodynamically stable
      patients with severe traumatic brain injury, pretransfusion hemoglobin<100g/l,
      non-bleeding and monitored through intracranial pressure and brain tissue partial
      pressure of oxygen (PtiO(2)) catheters were included. INTERVENTIONS: Transfusion
      of 1-2 units of red blood cells. MEASUREMENTS AND RESULTS: Ten sets of variables
      (pretransfusion, end of transfusion, and 1, 2, 3, 4, 5, 6, 12 and 24h after
      transfusion) were recorded, including: PtiO(2), cerebral perfusion pressure
      (CPP), end-tidal CO(2), peripheral saturation of oxygen, temperature, hemoglobin,
      lactate and PaO(2)/FiO(2) ratio. Transfusion was associated with an increase in
      PtiO(2) during a 6-h period, with a peak at 3h (26.2%; p=0.0001) in 78.3% of the
      patients. No relationship was observed between PtiO(2), CPP and hemoglobin
      increments. The relative increment in PtiO(2) at hour 3 was only correlated with
      baseline PtiO(2) (r(2) 0.166; p=0.001). All of the patients with basal
      PtiO(2)<15mmHg showed an increment in PtiO(2) versus 74.5% of patients with basal
      PtiO(2)>or=15mmHg (p<0.01, hour 3). CONCLUSIONS: Erythrocyte transfusion is
      associated with a variable and prolonged increment of cerebral tissue oxygenation
      in anemic patients with severe traumatic brain injury. Low baseline PtiO(2)
      levels (<15mmHg) could define those patients who benefit the most from
      erythrocyte transfusion.

PMID- 17019550
TI  - Dying at home: cultural and religious preferences.

PMID- 17019551
TI  - A good death: another break in the wall.

PMID- 17019552
TI  - End-of-life practice in Belgium and the new euthanasia law.

PMID- 17019553
TI  - Correlation of urinalysis and dipstick results with catheter-associated urinary
      tract infections in surgical ICU patients.
AB  - OBJECTIVE: To determine the utility of urinalysis and dipstick results in
      predicting urinary tract infections in catheterized ICU patients. DESIGN AND
      SETTING: Urine samples were collected for 4months from patients admitted a ten
      bed surgical ICU of an urban public teaching hospital designated by the state of
      New York as a level I trauma center. The correlation was analyzed between
      urinalysis and dipstick results from urine samples and subsequent quantitative
      culture results. PATIENTS: All patients with indwelling urinary catheters
      admitted to the ICU were considered eligible; 106 patients were enrolled, and 300
      individual urine samples were analyzed. MEASUREMENTS AND RESULTS: There were 44
      catheter-associated urinary tract infections. Nitrite presence was the best
      indicator of infection (91.8% specificity) but was not a reliable clinical test
      due to a sensitivity of 29.5% and positive and negative likelihood ratios of 3.52
      and 0.56, respectively. None of the other parameters (leukocyte esterase, white
      blood cell count, urobilinogen, presence of yeast or bacteria) were independently
      correlated with the culture results either individually or in combination.
      CONCLUSIONS: Based on our data we cannot recommend the use of urinalysis or
      dipstick in screening for potential catheter-associated urinary tract infections.

PMID- 17019554
TI  - The inability to consent in critical care research: emergency or impairment of
      cognitive function?

PMID- 17019555
TI  - Informed consent in clinical trials in critical care: experience from the PAC-Man
      Study.
AB  - OBJECTIVES: To identify the proportion of critically ill patients able to consent
      to participation in a randomised controlled trial (RCT) and to assess to what
      extent patient consent and relative assent processes could be conducted according
      to ethics committee permission. DESIGN: Descriptive study nested in an RCT.
      SETTING: Fifty-six UK intensive care units participating in the PAC-Man trial.
      PATIENTS AND PARTICIPANTS: First 500 patients consecutively enrolled into PAC
      Man. MEASUREMENT AND RESULTS: The outcome measures were patient consent and/or
      relative assent. Of the 498 patients included, 13 (2.6%) provided consent before
      randomisation. Of the remaining 485 patients, relative assent was obtained for
      394 patients (81.2%), and refused post-randomisation for 3 patients (0.6%). No
      relatives were available for 15 patients (3.1%), and it was unclear from
      documentation whether relative assent had been obtained for 73 patients (15.1%).
      Of the 482 patients who did not provide consent prior to randomisation, 188 (39%)
      survived. Of these, 175 (93.1%) gave retrospective informed consent, six (3.2%)
      refused, and seven (3.7%) did not regain mental competency. CONCLUSIONS: A very
      small proportion of patients were able to give consent before randomisation. Due
      to the high in-hospital mortality (60.6%), only around one third of the remaining
      patients could provide consent retrospectively. This study demonstrates
      difficulties experienced in obtaining consent from critically ill patients to
      participate in medical research and raises important issues about the ethical
      basis of the consent process in critical care.

PMID- 17019556
TI  - Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.
AB  - OBJECTIVE: Barbiturate therapy or hypothermia precludes proper diagnosis of brain
      death either clinically or by EEG. Specific intracranial flow patterns indicating
      cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler
      ultrasonography (TCD). The aim of this study was to assess the validity of TCD in
      confirming brain death. DESIGN: Meta-analysis of studies assessing the validity
      of TCD in confirming brain death. METHODS: A systematic review of articles in
      English on the diagnosis brain death by TCD, published between 1980 and 2004, was
      performed. An oscillating or reverberating flow and systolic spikes were
      considered to be compatible with CCA. The quality of each study was assessed
      using standardized methodological criteria. The literature was searched for any
      article reporting a false-positive result. RESULTS: Two high-quality and eight
      low-quality studies were included. Meta-analysis of the two high-quality studies
      showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97
      100%) to detect brain death. Meta-analysis of all ten studies showed a
      sensitivity of 89% and a specificity of 99%. In the literature we found two false
      positive results; however, in both patients brain-stem function did show brain
      death shortly thereafter. CONCLUSIONS: CCA by TCD in the anterior and posterior
      circulation predicted fatal brain damage in all patients; therefore, TCD can be
      used to determine the appropriate moment for angiography. Further research is
      needed to demonstrate that CCA by TCD on repeated examination can also predict
      brain death in all patients.

PMID- 17019557
TI  - Prognosis and risk factors of early onset pneumonia in ventilated patients with
      Guillain-Barre syndrome.
AB  - OBJECTIVE: Invasive mechanical ventilation is required in 30% of patients with
      Guillain-Barre syndrome (GBS) and is associated with pneumonia and increased
      mortality. Our objective was to determine the incidence, characteristics,
      outcomes, and risk factors of pneumonia in GBS patients receiving mechanical
      ventilation. DESIGN AND SETTING: Study of a prospective database in an intensive
      care unit of a university hospital. PATIENTS: The study included 81 patients who
      required intubation for GBS. Neurological findings, vital capacity, and signs of
      respiratory distress were recorded at admission and at intubation. A score
      predicting the risk of intubation (0-4) was calculated for each patient.
      Pneumonia was diagnosed based on predefined criteria and retrospectively
      confirmed by two observers. Early-onset pneumonia was defined as pneumonia
      diagnosed within 5 days after intubation. MEASUREMENTS AND RESULTS: Mean vital
      capacity was 57 +/- 22% of predicted at admission and 33 +/- 11% at intubation.
      Pneumonia developed in 63 patients (78%), including 48 with early-onset
      pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with
      pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress
      syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower
      risk of intubation (score < 2), and time from admission to intubation longer than
      2 days were associated with early-onset pneumonia. Time from admission to
      intubation was the only independent predictor in the multivariate logistic
      regression model. CONCLUSIONS: Early-onset pneumonia is a common and severe
      complication that is related to aspiration in patients with GBS. Delaying
      intubation may increase the risk of early-onset pneumonia.

PMID- 17019558
TI  - In-hospital cardiac arrest: incidence, prognosis and possible measures to improve
      survival.
AB  - DESIGN: Review. OBJECTIVE: Medical literature on in-hospital cardiac arrest
      (IHCA) was reviewed to summarise: (a) the incidence of and survival after IHCA,
      (b) major prognostic factors, (c) possible interventions to improve survival.
      RESULTS AND CONCLUSIONS: The incidence of IHCA is rarely reported in the
      literature. Values range between 1 and 5 events per 1,000 hospital admissions, or
      0.175 events/bed annually. Reported survival to hospital discharge varies from 0%
      to 42%, the most common range being between 15% and 20%. Pre-arrest prognostic
      factors: the prognostic value of age is controversial. Among comorbidities,
      sepsis, cancer, renal failure and homebound lifestyle are significantly
      associated with poor survival. However, pre-arrest morbidity scores have not yet
      been prospectively validated as instruments to predict failure to survive after
      IHCA. Intra-arrest factors: ventricular fibrillation/ventricular tachycardia
      (VF/VT) as the first recorded rhythm and a shorter interval between IHCA and
      cardiopulmonary resuscitation or defibrillation are associated with higher
      survival. However, VF/VT is present in only 25-35% of IHCAs. Short-term survival
      is also higher in patients resuscitated with chest compression rates above
      80/min. Interventions likely to improve survival include: early recognition and
      stabilisation of patients at risk of IHCA to enable prevention, faster and better
      in-hospital resuscitation and early defibrillation. Mild therapeutic hypothermia
      is effective as post-arrest treatment of out-of-hospital cardiac arrest due to
      VF/VT, but its benefit after IHCA and after cardiac arrest with non-VF/VT rhythms
      has not been clearly demonstrated.

PMID- 17019559
TI  - Benefits and risks of success or failure of noninvasive ventilation.
AB  - OBJECTIVE: Noninvasive ventilation (NIV) fails more frequently for de novo acute
      respiratory failure (de novo) than for cardiogenic pulmonary edema (CPE) or acute
      on-chronic respiratory failure (AOC). The impact of NIV failure and success was
      compared between de novo and CPE or AOC after adjustment for disease severity.
      SETTINGS: Patients requiring ventilatory support were enrolled in a prospective
      survey in 70 French ICUs. Of 1076 patients requiring ventilatory support, 524
      were eligible, including 299 de novo (NIV use, 30%) and 225 CPE-AOC (NIV use,
      55%). DESIGN AND ANALYSIS: Independent risk factors associated with mortality and
      length of stay were identified by logistic regression analysis. The adjusted
      outcome of NIV success or failure was compared to that with endotracheal
      intubation without NIV. RESULTS: NIV success was independently associated with
      survival in both de novo, adjusted OR 0.05 (95% CI 0.01-0.42), and CPE-AOC OR
      0.03 (CI 0.01-0.24). NIV failure was associated with ICU mortality in the de novo
      group (OR 3.24, CI 1.61-6.53) but not in the CPE-AOC group. Nosocomial pneumonia
      was less common in patients successful with NIV. NIV failure was associated with
      a longer ICU stay in CPE-AOC only. The overall use of NIV was independently
      associated with a better outcome only in CPE-AOC patients (OR 0.33, CI 0.15
      0.73). CONCLUSION: The effect of NIV differs between de novo and CPE-AOC patients
      because NIV failure is associated with increased mortality for de novo patients.
      This finding should raise a note of caution when applying NIV in this indication.

PMID- 17019560
TI  - Pattern of MAP kinases p44/42 and JNK activation by non-lethal doses of
      tributyltin in human natural killer cells.
AB  - Tributyltin (TBT) has been shown to disrupt the ability of natural killer (NK)
      cells to destroy tumor targets in vitro even at exposures of 25 nM for 24 h, but
      cell viability was not significantly impacted. Thus, evaluation of intracellular
      molecular events that regulate cell viability in TBT exposed NK cells are of
      interest. It has been suggested that activation of the mitogen-activated protein
      kinase (MAPK), c-Jun N-terminal kinase (JNK), may promote apoptosis while
      activation of the MAPK p44/42 may be crucial in mediating anti-apoptotic stimuli.
      However, it is well established that increases in pro-apoptotic BCL-2 family
      members, such as Bax, results in cell death. We have set out to study the effects
      of a range of TBT concentrations on the MAPKs, JNK and p44/42. Additionally, we
      examined the effects of TBT on the levels of pro-apoptotic proteins Bax and p53
      as well as anti-apoptotic protein Bcl-2. The results show that 300-25 nM TBT
      activated JNK within 10 min. MAPK p44/42 was also activated by 300-50 nM TBT
      within 10 min. These data show that while 300-200 nM TBT activates p44/42
      significantly more than JNK, the pattern of 100-25 nM TBT activation of these
      MAPKs may be similar. TBT exposure alters neither pro-apoptotic proteins Bax and
      p53 nor anti-apoptotic protein Bcl-2 levels at any exposure studied. The results
      suggest that exposure to TBT activated the anti-apoptotic regulatory p44/42
      pathway to a greater extent than the pro-apoptotic JNK pathway, which may explain
      to some extent how NK cell viability is maintained.

PMID- 17019561
TI  - Protective role of sulphated polysaccharides in abating the hyperlipidemic
      nephropathy provoked by cyclosporine A.
AB  - Cyclosporine A (CsA)-induced nephrotoxicity hampers the immense therapeutic
      potential of such a powerful immunosuppressant. The present study was conducted
      with an aim to explicate the contribution of sulphated polysaccharides (SPS) in
      abating the lipid abnormalities induced by CsA in the rat kidney. Hyperlipidemia
      associated with nephrotic syndrome may play a role in the worsening of renal
      function. Male albino Wistar rats sorted into four groups were used for the
      study. CsA was given at a dose of 25 mg/kg body weight, orally for 21 days.
      Significant alterations in the lipid profile as well an increase in the activity
      of cholesterol ester synthase, coupled with a decrease in cholesterol ester
      hydrolase and lipoprotein lipase enzyme activities were noted in the plasma and
      kidneys of CsA-administered rats. A marked increase in the lipoprotein fractions,
      low-density lipoprotein (LDL) and very low density lipoprotein (VLDL), along with
      a decrease in the HDL level were found in CsA-administered rats. The degree of
      nephrotoxicity allied with lipid discrepancies was evident from augmented urinary
      excretion of urea, uric acid and creatinine. Further, an enhanced susceptibility
      of the apo B-containing lipoproteins (LDL + VLDL) to oxidation in vitro, induced
      by copper ions was also found in the plasma of CsA given groups. While SPS co
      treated groups (5 mg/kg body weight, subcutaneously) revealed a normalized lipid
      profile and lipid metabolizing enzymes, the supplementation of SPS also brought
      back the elevated urinary constituents close to that of the controls and
      substantially minimized the oxidative changes. With these observations, it may be
      concluded herein that SPS may be an ideal choice as a renoprotective and
      hypolipidemic agent against CsA-induced hyperlipidemic nephropathy.

PMID- 17019562
TI  - Internal dose-effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      gonadotropin-primed weanling rat model.
AB  - Single sc injection of 5 IU equine chorionic gonadotropin (eCG) induces ovulation
      in weanling female rats 3 days later. It has been shown that treatment with
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 24 h before eCG injection reduces eCG
      stimulated ovarian hypertrophy and inhibits ovulation. The present study intended
      to compare internal dose-effects of TCDD between these endpoints and
      representative endpoints for TCDD toxicity, such as weights of the liver and
      thymus, in weanling female rats given orally 0, 1, 4 or 16 microg/kg TCDD 24 h
      before eCG injection on postnatal day 25. Measurement of plasma TCDD
      concentrations by ELISA at 6, 72 and 96 h after TCDD revealed that significant
      levels of TCDD were maintained in systemic circulation until 96 h (on the day of
      induced ovulation) with the highest level at 6 h after TCDD treatment. Ovarian
      TCDD concentrations varied similarly and tended to be higher than those in the
      thymus at all time points, whereas hepatic concentrations of TCDD were the
      highest among the tissues. Although > or = 4 microg/kg TCDD affected the weights
      of the thymus and liver, no differences were observed in ovarian weights at any
      time point or in ovulation between corn oil-treated and TCDD-treated groups.
      Furthermore, ovarian levels of representative mRNAs in follicles were not
      affected by TCDD treatment. Since TCDD increased the amount of cytochrome P450
      1A1 mRNA in the ovary, the administered TCDD stimulated the aryl hydrocarbon
      receptor-signaling pathway. From these results, we concluded that thymus weights
      of weanling female rats responded to TCDD at a lower internal dose as compared
      with that ovarian hypertrophy and follicular growth from early antral stage to
      ovulation would respond to.

PMID- 17019563
TI  - Effects of crude adlay hull acetone extract on corticosterone release from rat
      zona fasciculata-reticularis cells.
AB  - Adlay is a grass crop which has been used in traditional Chinese medicine and
      also as a nourishing food. It has been shown to posses anti-allergic,
      antimutagenic and hypolipemic effects. However, the effects and action mechanisms
      of crude adlay hull acetone extract (AHA) on adrenal zona fasciculata-reticularis
      (ZFR) cells are still unclear. This study explored the effects of AHA on
      corticosterone release. ZFR cells were incubated with AHA in the presence or
      absence of adrenocorticotropin (ACTH), 8-bromo-cyclic 3': 5'- adenosine
      monophosphate (8-Br-cAMP), forskolin (FSK), 25-hydroxy cholesterol (25-OH
      cholesterol), pregnenolone, progesterone or deoxycorticosterone. The
      concentrations of corticosterone or pregnenolone in the media were measured by
      radioimmunoassay (RIA). The cells were used to measure the expression of
      steroidogenic acute regulatory (StAR) protein by Western blot. The present data
      demonstrated that: (1) AHA inhibited ACTH-, 8-Br-cAMP-, forskolin-, 25-OH
      cholesterol-, pregnenolone-, progesterone- or deoxycorticosterone-stimulated
      corticosterone release; (2) AHA (800 microg/ml) caused more pregnenolone release
      in control group, but not in 25-OH-cholesterol, trilostane or 25-OH
      cholesterol+trilostane group; (3) kinetic study showed an uncompetitive
      inhibition model of AHA to P450 side chain cleavage enzyme (P450scc); (4) kinetic
      study showed a noncompetitive inhibition model of AHA to 11beta-hydroxylase; and
      (5) AHA inhibited the expression of StAR protein. These results suggest that AHA
      acts directly upon rat ZFR cells to diminish corticosterone release. These
      results indicate the inhibitory mechanism of AHA mediates through an inhibition
      of the activities of the post-cAMP corticosterone synthesis enzymes, i.e. 3beta
      HSD, 21-hydroxylase, 11beta-hydroxylase, and inhibition of StAR protein
      expression.

PMID- 17019564
TI  - Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic
      patients is not related to antipsychotic treatment but it suggests an illness
      trait.
AB  - INTRODUCTION: Drug induced parkinsonism (DIP) is directly related to dopamine D2
      receptor blockade. However, there are many references describing parkinsonian
      signs (PS) in naive-patients. In our previous study, we observed lower DAT
      binding in a group of first-episode schizophrenic patients after short-term
      treatment with risperidone, compared with age-matched healthy controls. AIM: To
      clarify if DAT decrease could be an illness trait, excluding the effect of
      antipsychotics on DAT availability, and to determine whether DAT availability
      before treatment with antipsychotics may predict subsequent development of PS.
      MATERIALS AND METHODS: A new series of 20 neuroleptic-naive schizophrenic
      patients and 15 healthy subjects was recruited. SPECT with [(123)I] FP-CIT
      (DaTSCAN(R)) was performed before starting antipsychotics and after 4 weeks of
      treatment. PS and psychopathological status were assessed by the Simpson-Angus
      (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using
      ROIs placed in the caudate, putamen and occipital cortex. RESULTS: Schizophrenic
      patients showed lower DAT binding compared with the healthy subjects at baseline
      (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight
      schizophrenic patients of the DIP group were symptomatic for PS at baseline, in
      comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were
      observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at
      endpoint (p=0.984). Finally, no differences between baseline-endpoint DAT binding
      were observed, neither in the DIP group (p=0.767) nor in the NoDIP group
      (p=0.093). CONCLUSION: Our new series of first-episode naive-schizophrenic
      patients (1) points out DAT dysfunction as an illness trait due to the
      significantly lower DAT binding in schizophrenic patients in comparison to
      healthy subjects; (2) supports the results of other authors who describe PS in
      never-treated patients; (3) confirms that [(123)I] FP-CIT does not allow us to
      predict which patients will develop parkinsonism due to the lack of differences
      between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics
      on DAT due to the lack of differences in [(123)I] FP-CIT before and after a 4
      week-treatment period.

PMID- 17019565
TI  - Impaired performance of alpha7 nicotinic receptor knockout mice in the five
      choice serial reaction time task.
AB  - RATIONALE: Nicotinic receptors have been implicated in attentional performance.
      Nicotine can improve attention in animals and humans, but knowledge about
      relevant receptor subtypes is very limited. OBJECTIVES: The aim was to examine
      the role of alpha7 receptors in attentional performance of mice and in effects of
      nicotine. MATERIALS AND METHODS: Mice with targeted deletion of the gene coding
      for the alpha7 subunit of nicotinic receptors and wild-type controls were trained
      on a five-choice serial reaction time task with food reinforcers presented under
      varying parametric conditions. Nicotine was administered in a range of doses
      (0.001-1.0 mg/kg sc), including those reported to enhance attentional
      performance. RESULTS: Initially the alpha7(-/-) (knockout) mice responded less
      accurately and made more anticipatory responses. After task parameters were
      altered so that the time allowed for responding was reduced and anticipatory
      (impulsive) responses were punished by a time-out, the pattern of performance
      deficits changed; there were increased omission errors in alpha7(-/-) mice but
      normal levels of accuracy and anticipatory responding. Nicotine did not improve
      any measure of performance, either with the original training parameters or after
      retraining; the largest dose used (1.0 mg/kg) produced a general impairment of
      responding in alpha7(-/-) and wild-type mice. CONCLUSIONS: alpha7 nicotinic
      receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a
      possible role for alpha7 receptors in attentional processing. However,
      identification of a protocol for assessing attention-enhancing effects of
      nicotine in mice may require further modifications of test procedures or the use
      of different strains of animal.

PMID- 17019566
TI  - Sex differences in the neurochemical and functional effects of MDMA in Sprague
      Dawley rats.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been
      associated with acute toxicities and persistent depletion of the neurotransmitter
      serotonin (5-HT). OBJECTIVES: This study investigates whether sex differences in
      the acute and long-term effects of MDMA exist. METHODS: Male and female rats
      received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored
      on days 1 and 4. Locomotor activity was measured in a second cohort of animals on
      days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in
      a plus maze task and brain levels of serotonin (5-HT) and the serotonin
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort
      of animals 2 weeks after the last MDMA treatment. RESULTS: Locomotor activity and
      temperature increased after MDMA administration on day 1. The drug-induced
      increases in temperature but not locomotion attenuated with repeated MDMA
      administration. Male and female MDMA-treated rats spent less time in the open
      arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions
      2 weeks after the end of treatment. Temperature effects of MDMA and persistent
      effects on plus maze and brain serotonin content were similar in males and
      females. In contrast, females exhibited markedly greater locomotor stimulation
      after acute MDMA and also showed sensitization to an acute challenge 2 weeks
      later. CONCLUSIONS: MDMA elicits substantially greater locomotor activation in
      female rats than in males, but persistent effects on anxiety and serotonin
      content were similar in males and females.

PMID- 17019568
TI  - Reinforcement schedule effects in rats trained to discriminate 3,4
      methylenedioxymethamphetamine (MDMA) or cocaine.
AB  - RATIONALE: Relatively few studies have compared the discriminative stimulus
      effects of 3,4-methylenedioxymethamphetamine (MDMA) and cocaine, and findings
      from different laboratories are somewhat inconsistent. One possible reason for
      discrepant results may be the use of different reinforcement schedules during
      discrimination training. OBJECTIVE: The present study compared fixed ratio (FR)
      20 and variable interval (VI) 15-s reinforcement schedules to determine their
      influence on discrimination acquisition, response rates, frequency of
      reinforcements, and stimulus generalization in rats trained to discriminate
      cocaine or MDMA. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats were
      trained to discriminate cocaine (10 mg/kg; n=16) or MDMA (1.5 mg/kg; n=16) from
      saline under either a FR 20 or a VI 15-s schedule of food reinforcement. Stimulus
      generalization tests were conducted with a range of doses of cocaine, MDMA, d
      amphetamine, and lysergic acid diethylamide in all four training groups. RESULTS:
      The FR 20 schedule facilitated more rapid discrimination acquisition compared to
      the VI 15-s schedule and established differential response rates and frequency of
      reinforcement under drug and vehicle conditions. However, reinforcement schedule
      had little influence on stimulus generalization between MDMA and cocaine. Cocaine
      produced partial substitution for MDMA in both training groups (FR 20, 51%; VI 15
      s, 58%). Likewise, MDMA produced only partial substitution for cocaine in both
      training groups (FR 20, 40%; VI 15-s, 72%). CONCLUSIONS: The present findings
      suggest that the number of sessions required to establish discriminative stimulus
      control varies with different reinforcement schedules. Nevertheless, training
      schedules alone do not appear to have significant effects on stimulus
      generalization between MDMA and cocaine.

PMID- 17019569
TI  - Operant responding for conditioned and unconditioned reinforcers in rats is
      differentially enhanced by the primary reinforcing and reinforcement-enhancing
      effects of nicotine.
AB  - RATIONALE: Nicotine self-administration in rats is modest when response
      contingent nicotine infusions are delivered alone (primary reinforcement) but
      robust when nicotine infusions are combined with a mildly reinforcing non
      pharmacological stimulus. Furthermore, response-independent (non-contingent)
      nicotine administration also elevates responding for that same non
      pharmacological stimulus, suggesting that in addition to primary reinforcement,
      nicotine can enhance the incentive value of other reinforcers. OBJECTIVES: In
      this study, we tested the hypothesis that the reinforcement-enhancing effects of
      non-contingent nicotine are more dependent on the reinforcing strength of the non
      pharmacological stimulus than are the effects of contingent nicotine. MATERIALS
      AND METHODS: A weakly reinforcing light-tone stimulus was established as a
      conditioned reinforcer by repeated pairings with sucrose for some rats, or by
      delivery in an explicitly unpaired design with sucrose to other rats.
      Subsequently, both groups lever pressed for the stimulus with contingent
      nicotine, non-contingent nicotine (0.06 mg kg(-1) per infusion, freebase), or non
      contingent saline, according to fixed ratio and progressive ratio reinforcement
      schedules. RESULTS: Compared to sucrose-unpaired training, repeated association
      with sucrose established the light-tone stimulus as a robust conditioned
      reinforcer. Contingent and non-contingent nicotine equally elevated responding
      for this conditioned stimulus. Conversely, for the less reinforcing (sucrose
      unpaired) stimulus contingent nicotine more effectively elevated behavior
      compared to non-contingent nicotine. CONCLUSIONS: The reinforcement-enhancing
      effect of nicotine increases behavior controlled by both conditioned and
      unconditioned reinforcers; however, for less salient stimuli associative
      processes derived from the primary reinforcing effects of contingent nicotine may
      also be important. These data suggest that nicotine present in tobacco may
      differentially modulate stimulus-driven behavior in smokers.

PMID- 17019567
TI  - Toward a model of drug relapse: an assessment of the validity of the
      reinstatement procedure.
AB  - BACKGROUND AND RATIONALE: The reinstatement model is widely used to study relapse
      to drug addiction. However, the model's validity is open to question. OBJECTIVE:
      We assess the reinstatement model in terms of criterion and construct validity.
      RESEARCH HIGHLIGHTS AND CONCLUSIONS: We find that the reinstatement model has
      adequate criterion validity in the broad sense of the term, as evidenced by the
      fact that reinstatement in laboratory animals is induced by conditions reported
      to provoke relapse in humans. The model's criterion validity in the narrower
      sense, as a medication screen, seems promising for relapse to heroin, nicotine,
      and alcohol. For relapse to cocaine, criterion validity has not yet been
      established primarily because clinical studies have examined medication's effects
      on reductions in cocaine intake rather than relapse during abstinence. The
      model's construct validity faces more substantial challenges and is yet to be
      established, but we argue that some of the criticisms of the model in this regard
      may have been overstated.

PMID- 17019570
TI  - Effects of selective dopamine D1-like and D2-like agonists on prepulse inhibition
      of startle in inbred C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice.
AB  - RATIONALE: Prepulse inhibition (PPI) and locomotor activity have been used to
      investigate the effects of antipsychotic and stimulant drugs and their underlying
      dopaminergic mechanisms. Whereas D2-like agonists consistently decreased PPI and
      increased locomotion in rats in previous studies, we recently reported that these
      hallmark behavioral effects were not observed in several mouse strains.
      Nevertheless, we recently identified three mouse strains (C3H/HeJ, SPRET/EiJ, and
      CAST/EiJ) that exhibited locomotor hyperactivity after administration of a
      selective D2-like agonist. OBJECTIVES: We hypothesized that, similar to rats,
      C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice would exhibit decreased PPI after
      administration of a D2-like agonist. RESULTS: Administration of the D2-like
      agonist quinelorane dose-dependently decreased PPI in C3H/HeJ and SPRET/EiJ mice.
      In agreement with previous reports in rats and other strains of mice, the D1-like
      agonist R-6-Br-APB also decreased PPI in C3H/HeJ and SPRET/EiJ mice. In contrast,
      CAST/EiJ mice had low levels of baseline PPI in our standard test session and
      quinelorane and R-6-Br-APB had no effect on PPI under those conditions. Through
      the optimization of session parameters, we obtained higher baseline PPI in
      CAST/EiJ mice and found that quinelorane but not R-6-Br-APB decreased PPI. In
      summary, similar to rats and unlike previous published reports on several strains
      of mice, we have now identified three strains of mice in which a D2-like agonist
      decreased PPI. CONCLUSIONS: The C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice may more
      closely mirror the Sprague Dawley rat than most other mouse strains and may
      confer advantages in cross-species behavioral pharmacology studies related to D2
      receptor function.

PMID- 17019572
TI  - A microchip sensor for calcium determination.
AB  - A newly designed glass-PDMS microchip-based sensor for use in the determination
      of Ca(2+) ions has been developed, utilizing reflectance measurements from
      arsenazo III (1,8-dihydroxynaphthalene-3,6-disulfonic acid-2,7-bis[(azo-2)-phenyl
      arsenic acid]) immobilized on the surface of polymer beads. The beads, produced
      from cross-linked poly(p-chloromethylstyrene) (PCMS), were covalently modified
      with polyethylenimine (PEI) to which the Arsenazo III could be adsorbed. The
      maximum amount of Arsenazo III which could be immobilized onto the PEI-attached
      PCMS beads was found to be 373.71 mg g(-1) polymer at pH 1. Once fabricated, the
      beads were utilized at the detection point of the microfluidic sensor device with
      a fiber optic assembly for reflectance measurements. Samples were mobilized past
      the detection point in the sensor where they interact with the immobilized dye.
      The sensor could be regenerated and re-used by rinsing with HCl solution. The pH,
      voltage, linear range, and the effect of interfering ions were evaluated for
      Ca(2+) determination using this microchip sensor. At the optimum potential, 0.8
      kV, and pH 9.0, the linear range of the microchip sensor was 3.57 x 10(-5) - 5.71
      x 10(-4) M Ca(2+), with a limit of detection (LOD) of 2.68 x 10(-5) M. The
      microchip biosensor was then applied for clinical analysis of calcium ions in
      serum with good results.

PMID- 17019573
TI  - The role of quorum sensing in the pathogenicity of the cunning aggressor
      Pseudomonas aeruginosa.
AB  - Recent decades have revealed that many bacterial species are capable of
      communicating with each other, and this observation has been largely responsible
      for a paradigm shift in microbiology. Whereas it was previously believed that
      bacteria lived as individual cells, it is now acknowledged that bacteria
      preferentially live in communities in the form of primitive organisms in which
      the behavior of individual cells is coordinated by cell-cell communication, known
      as quorum sensing (QS). Bacteria use QS for regulation of the processes involved
      in their interaction with each other, their environment, and, particularly,
      higher organisms We have focused on Pseudomonas aeruginosa, an opportunistic
      pathogen producing more than 30 QS-regulated virulence factors. P. aeruginosa
      causes several types of nosocomial infection, and lung infection in cystic
      fibrosis (CF) patients. We review the role of QS in the protective mechanisms of
      P. aeruginosa and show how disruption of the QS can be used as an approach to
      control this cunning aggressor.

PMID- 17019571
TI  - The acute effects of cannabinoids on memory in humans: a review.
AB  - RATIONALE: Cannabis is one of the most frequently used substances. Cannabis and
      its constituent cannabinoids are known to impair several aspects of cognitive
      function, with the most robust effects on short-term episodic and working memory
      in humans. A large body of the work in this area occurred in the 1970s before the
      discovery of cannabinoid receptors. Recent advances in the knowledge of
      cannabinoid receptors' function have rekindled interest in examining effects of
      exogenous cannabinoids on memory and in understanding the mechanism of these
      effects. OBJECTIVE: The literature about the acute effects of cannabinoids on
      memory tasks in humans is reviewed. The limitations of the human literature
      including issues of dose, route of administration, small sample sizes, sample
      selection, effects of other drug use, tolerance and dependence to cannabinoids,
      and the timing and sensitivity of psychological tests are discussed. Finally, the
      human literature is discussed against the backdrop of preclinical findings.
      RESULTS: Acute administration of Delta-9-THC transiently impairs immediate and
      delayed free recall of information presented after, but not before, drug
      administration in a dose- and delay-dependent manner. In particular, cannabinoids
      increase intrusion errors. These effects are more robust with the inhaled and
      intravenous route and correspond to peak drug levels. CONCLUSIONS: This profile
      of effects suggests that cannabinoids impair all stages of memory including
      encoding, consolidation, and retrieval. Several mechanisms, including effects on
      long-term potentiation and long-term depression and the inhibition of
      neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been
      implicated in the amnestic effects of cannabinoids. Future research in humans is
      necessary to characterize the neuroanatomical and neurochemical basis of the
      memory impairing effects of cannabinoids, to dissect out their effects on the
      various stages of memory and to bridge the expanding gap between the humans and
      preclinical literature.

PMID- 17019574
TI  - Bacterial quorum sensing and interference by naturally occurring biomimics.
AB  - Bacteria are able to coordinate gene expression as a community through the
      secretion and detection of signalling molecules so that the members of the
      community can simultaneously express specific behaviours. This mechanism of
      regulation of behaviour appears to be a key trait for adaptation to specific
      environments and has been shown to regulate a variety of important phenotypes,
      from virulence factor production to biofilm formation to symbiosis related
      behaviours such as bioluminescence. The ability to communicate and communally
      regulate gene expression is hypothesised to have evolved as a way for organisms
      to delay expression of phenotypes until numerical supremacy is reached. For
      example, in the case of infection, if an invading microorganism were to express
      virulence factors too early, the host may be able to mount a successful defence
      and repel the invaders. There is growing evidence that bacterial quorum sensing
      (QS) systems are involved in cross-kingdom signalling with eukaryotic organisms
      and that eukaryotes are capable of actively responding to bacteria in their
      environment by detecting and acting upon the presence of these signalling
      molecules. Likewise, eukaryotes produce compounds that can interfere with QS
      systems in bacteria by acting as agonists or antagonists. An exciting new field
      of study, biomimetics, takes inspiration from nature's models and attempts to
      design solutions to human problems, and biomimics of QS systems may be one such
      solution. This article presents the acylated homoserine lactone and autoinducer 2
      QS systems in bacteria, the means of intercepting or interfering with bacterial
      QS systems evolved by eukaryotes, and the rational design of synthetic
      antagonists.

PMID- 17019575
TI  - Raman spectroscopic investigation of the antimalarial agent mefloquine.
AB  - The antimalarial agent mefloquine was investigated using Fourier transform near
      infrared (FT NIR) Raman and FT IR spectroscopy. The IR and Raman spectra were
      calculated with the help of density functional theory (DFT) and a very good
      agreement with the experimental spectra was achieved. These DFT calculations were
      applied to unambiguously assign the prominent features in the experimental
      vibrational spectra. The calculation of the potential energy distribution (PED)
      and the atomic displacements provide further valuable insight into the molecular
      vibrations. The most prominent NIR Raman bands at 1,363 cm(-1) and 1,434 cm(-1)
      are due to C=C stretching (in the quinoline part of mefloquine) and CH(2) wagging
      vibrations, while the most intense IR peaks at 1,314 cm(-1); 1,147 cm(-1); and
      1,109 cm(-1) mainly consist of ring breathings and deltaCH (quinoline); C-F
      stretchings; and asymmetric ring breathings, C-O stretching as well as CH(2)
      twisting/rockings located at the piperidine moiety. Since the active agent
      (mefloquine) is usually present in very low concentrations within the biological
      samples, UV resonance Raman spectra of physiological solutions of mefloquine were
      recorded. By employing the detailed non-resonant mode assignment it was also
      possible to unambiguously identify the resonantly enhanced modes at 1,619 cm(-1),
      1,603 cm(-1) and 1,586 cm(-1) in the UV Raman spectra as high symmetric C=C
      stretching vibrations in the quinoline part of mefloquine. These spectroscopic
      results are important for the interpretation of upcoming in vitro and in vivo
      mefloquine target interaction experiments.

PMID- 17019576
TI  - Electrochemical studies of (-)-epigallocatechin gallate and its interaction with
      DNA.
AB  - In this paper, an electrochemical investigation of (-)-epigallocatechin gallate
      (EGCG) and its interaction with DNA is presented. Via an electrochemical approach
      assisted by ultraviolet-visible (UV-Vis) spectroscopy, we propose that EGCG can
      intercalate into DNA strands forming a nonelectroactive complex, which results in
      the decrease of the anodic peak current of EGCG. Meanwhile, an electrochemical
      study with the DNA-Cu(II)-EGCG system shows that damage to DNA can be recognized
      electrochemically via the increase in the anodic peak current resulting from the
      oxidation of guanine and adenine bases. The damage can also be recognized
      spectrophotometrically via an increase in the 260 nm absorption band. In
      addition, it was found that EGCG is able to discriminate dsDNA from ssDNA, making
      a potential electrochemical indicator for the detection of DNA hybridization
      events. A rapid and convenient method of detecting EGCG was also developed in
      this work.

PMID- 17019577
TI  - Determination of the titanium content of human transferrin by inductively-coupled
      plasma-atomic-emission spectroscopy.
AB  - We report a simple method that combines dialysis, as a purification method, with
      the multielement capability of ICP to determine the titanium-to-transferrin mole
      ratio at physiological pH, under buffer conditions. The method, by means of which
      titanium and transferrin are determined simultaneously, enabled us to assess the
      binding capacities of different titanocene complexes.

PMID- 17019578
TI  - Comparison of the efficiencies of different types of adsorbents at trapping
      currently used pesticides in the gaseous phase using the technique of high-volume
      sampling.
AB  - Atmospheric samples were collected in an urban area (Strasbourg centre) in
      spring/summer 2004, in order to determine the concentrations of different
      pesticides in the gaseous and particulate phases and to compare the efficiencies
      of different adsorbents at trapping the gaseous phase. Two high-volume samplers
      were placed next to each other in the botanical garden in the centre of
      Strasbourg. Air sampling was carried out using a glass fibre filter and different
      adsorbents for 48 hrs. The following adsorbents and combinations of adsorbents
      were compared: XAD-2 with PUF, XAD4 with PUF, XAD-2 with a PUF-XAD2-PUF sandwich,
      PUF with a PUF-XAD4-PUF sandwich. In order of efficiency at trapping pesticides,
      the "sandwiches" are the most efficient, followed by XAD-2 and XAD-4 resins.
      However, although the "sandwiches" are slightly better at trapping than XAD-2,
      the use of XAD-2 is recommended for technical reasons. The PUFs are the least
      efficient at trapping. Among the 27 pesticides analysed, trifluralin, alachlor,
      metolachlor and captan were the most concentrated pesticides, followed by
      lindane, alpha-endosulfan and diflufenican. This result is in accordance with
      farming activity in the Alsace region, where the pesticides that are used on
      large crops (maize, cereals) are applied in the greatest quantities. Vineyards
      are another important form of agriculture in Alsace, but the quantities of
      pesticides applied in comparison to those used on large crops is very low, which
      explains the low detection of vineyard pesticides in air samples observed here.
      The concentrations are depend on the identities and properties of the pesticides
      analysed, but on the whole they remain rather low. It is important to perform
      measurements like these in the urban environment, as these compounds can be
      harmful to human health and the environment and so their concentrations need to
      be monitored.

PMID- 17019580
TI  - Towards automated, miniaturized and solvent-free sample preparation methods.

PMID- 17019579
TI  - Analysis of carbamazepine and its active metabolite, carbamazepine-10,11-epoxide,
      in human plasma using high-performance liquid chromatography.
AB  - A sensitive method based on high-performance liquid chromatography (HPLC) with
      ultraviolet (UV) detection was developed for the determination of carbamazepine
      (CBZ) and one of its active metabolites, carbamazepine-10,11-epoxide (CBZ-E) in
      human plasma. CBZ, CBZ-E and the internal standard (IS) 10,11
      dihydrocarbamazepine were extracted from human plasma into methyl tert-butyl
      ether. CBZ, CBZ-E and the IS were successfully separated on an RP C18 column with
      a mobile phase of acetonitrile:methanol:water (18:19:63, v/v/v) and monitored via
      UV detection at 210 nm. The calibration curves were linear over the concentration
      ranges of 0.01-10 microg/mL for CBZ and 0.005-5 microg/mL for CBZ-E in human
      plasma, respectively. The method displayed excellent sensitivity, precision and
      accuracy, and was successfully applied to the quantification of CBZ and CBZ-E in
      human plasma after oral administration of a single 200 mg CBZ CR tablet. This
      method is suitable for bioequivalence studies following single doses given to
      healthy volunteers.

PMID- 17019581
TI  - Sediment certified reference materials for the determination of polychlorinated
      biphenyls and organochlorine pesticides from the National Metrology Institute of
      Japan (NMIJ).
AB  - Two marine sediment certified reference materials, NMIJ CRM 7304-a and 7305-a,
      have been issued by the National Metrology Institute of Japan in the National
      Institute of Advanced Industrial Science and Technology (NMIJ/AIST) for the
      determination of polychlorinated biphenyls (PCBs) and organochlorine pesticides
      (OCPs). The raw materials of the CRMs were collected from a bay near industrial
      activity in Japan. Characterization of these CRMs was conducted by NMIJ, where
      the sediments were analyzed using multiple analytical methods such as pressurized
      liquid extraction (PLE), microwave-assisted extraction (MAE), saponification,
      Soxhlet extraction, supercritical fluid extraction (SFE), and ultrasonic
      extraction; the target compounds were determined by one of the primary methods of
      measurements, isotope dilution-mass spectrometry (ID-MS). Certified values have
      been provided for 14 PCB congeners (PCB numbers 3, 15, 28, 31, 70, 101, 105, 138,
      153, 170, 180, 194, 206, 209) and 4 OCPs (gamma-HCH, 4,4'-DDT, 4,4'-DDE, 4,4'
      DDD) in both CRMs. NMIJ CRM 7304-a has concentrations of the contaminants that
      are a factor of 2-15 greater than in CRM 7305-a. Both CRMs have information
      values for PCB homolog concentrations determined by collaborative analysis using
      a Japanese official method for determination of PCBs. The total PCB
      concentrations in the CRMs are approximately 920 and 86 microg kg(-1) dry mass
      respectively.

PMID- 17019582
TI  - Optical biochemical sensor for determining hydroperoxides in nonpolar organic
      liquids as archetype for sensors consisting of amphiphilic conetworks as
      immobilisation matrices.
AB  - This paper reports the successful design of a prototype of an optical biochemical
      sensor for the determination of hydroperoxides in nonpolar organic liquids. The
      sensor consists of a matrix of an amphiphilic polymer conetwork (APCN), a novel
      class of very promising polymeric materials for easy preparation of biochemical
      sensor matrices. APCNs are characterised by nanoscopic phase separation between
      the hydrophilic and the hydrophobic phases. For medium ratios of conetwork
      composition, the domains of both phases are interconnected both on the surface of
      the conetworks and throughout the bulk. The APCNs have peculiar swelling
      properties-the hydrophilic phase swells in hydrophilic media and the hydrophobic
      phase swells in hydrophobic media. In both types of media dissolved reagents can
      diffuse from the solution into the swollen phase of the polymeric conetwork. This
      enables loading of the hydrophilic phase of the APCNs with enzymes and indicator
      reagents by simple impregnation. Hydrophobic analytes can diffuse into the
      polymeric conetwork via its hydrophobic phase and react with indicator reagents
      immobilised in the hydrophilic phase at the huge internal interface between the
      two opposite phases.To prepare the described hydroperoxide-sensitive biosensors,
      we used APCN films consisting of 58% (w/w) poly(2-hydroxyethyl acrylate) (PHEA)
      as hydrophilic chains and 42% (w/w) polydimethylsiloxane (PDMS) as hydrophobic
      linkers. Horseradish peroxidase (HRP) and diammonium 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonate) (ABTS) as indicator reagent were co-immobilised
      in this optically clear and transparent matrix. In this feasibility study the
      conditions investigated were principally those relevant to characterisation of
      the innovative matrix material and the disposable biosensor produced from it; the
      biosensor was not optimised. Sensitivity toward tert-butylhydroperoxide (tBuOOH)
      dissolved in n-heptane was acceptable, between approximately 1 and at least 50
      mmol L(-1), even in the dry state. The response time was 1.7 to 5.0 min. No
      leaching of immobilised reagents was observed during a period of at least one
      hour. Pre-swelling the sensors with water increased the reaction rate and the
      total turnover number of the enzyme. In a dry atmosphere at 4 degrees C the
      sensors were found to be stable for at least two weeks.

PMID- 17019583
TI  - Near-infrared spectroscopy (NIRS) reflectance technology for the determination of
      tocopherols in alfalfa.
AB  - The vitamin E (alpha- and (beta+gamma)-tocopherol) contents present in alfalfa
      (fresh or dehydrated) were analysed using near-infrared spectroscopy (NIRS)
      technology together with a remote reflectance fibre-optic probe. The range of
      vitamin E was 0.55-5.16 mg/100 g for alpha-tocopherol and 0.07-0.48 for
      (beta+gamma)-tocopherol. The regression method employed was modified partial
      least squares (MPLS). The equations developed using the fibre-optic probe for 69
      samples of alfalfa (dehydrated and fresh) to determine the content of vitamin E
      in feeds had multiple correlation coefficients (RSQs) and prediction corrected
      standard errors (SEP (C)) of 0.946 and 0.321 mg/100 g for alpha-tocopherol and
      0.956 and 0.022 mg/100 g for (beta+gamma)-tocopherol. The predicted values of
      vitamin E in feeds using NIRS technology applying the fibre-optic probe directly
      on the sample with neither previous treatment nor manipulation are comparable to
      those obtained using the chemical method, which included alkaline hydrolysis and
      hexane extraction of the vitamin from the unsaponifiable fraction before
      chromatographic determination.

PMID- 17019584
TI  - Advances in analytical techniques for environmental analysis.

PMID- 17019585
TI  - Advances in the environmental analysis of polychlorinated naphthalenes and
      toxaphene.
AB  - Recent advances in the analysis of the chlorinated environmental pollutants
      polychlorinated naphthalenes (PCNs) and toxaphene are highlighted in this review.
      Method improvements have been realized for PCNs over the past decade in isomer
      specific quantification, peak resolution, and the availability of mass-labeled
      standards. Toxaphene method advancements include the application of new capillary
      gas chromatographic (GC) stationary phases, mass spectrometry (MS), especially
      ion trap MS, and the availability of Standard Reference Materials that are value
      assigned for total toxaphene and selected congener concentrations. An area of
      promise for the separation of complex mixtures such as PCNs and toxaphene is the
      development of multidimensional GC techniques. The need for continued
      advancements and efficiencies in the analysis of contaminants such as PCNs and
      toxaphene remains as monitoring requirements for these compound classes are
      established under international agreements.

PMID- 17019586
TI  - Analysis of polycyclic aromatic hydrocarbons (PAHs) in environmental samples: a
      critical review of gas chromatographic (GC) methods.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are frequently measured in the atmosphere
      for air quality assessment, in biological tissues for health-effects monitoring,
      in sediments and mollusks for environmental monitoring, and in foodstuffs for
      safety reasons. In contemporary analysis of these complex matrices, gas
      chromatography (GC), rather than liquid chromatography (LC), is often the
      preferred approach for separation, identification, and quantification of PAHs,
      largely because GC generally affords greater selectivity, resolution, and
      sensitivity than LC. This article reviews modern-day GC and state-of-the-art GC
      techniques used for the determination of PAHs in environmental samples. Standard
      test methods are discussed. GC separations of PAHs on a variety of capillary
      columns are examined, and the properties and uses of selected mass spectrometric
      (MS) techniques are presented. PAH literature on GC with MS techniques, including
      chemical ionization, ion-trap MS, time-of-flight MS (TOF-MS), and isotope-ratio
      mass spectrometry (IRMS), is reviewed. Enhancements to GC, for example large
      volume injection, thermal desorption, fast GC, and coupling of GC to LC, are also
      discussed with regard to the determination of PAHs in an effort to demonstrate
      the vigor and robustness GC continues to achieve in the analytical sciences.

PMID- 17019587
TI  - Standard reference materials (SRMs) for measurement of inorganic environmental
      contaminants.
AB  - NIST has developed an extensive collection of environmental SRMs, starting with
      fuel and biologically related materials in the late 1960s and now encompassing
      all sectors of environmental research. Advances in analytical methodology,
      including multi-element isotope-dilution mass spectrometry (IDMS) and expanded
      instrumental neutron-activation analysis (INAA) capabilities, enable value
      assignment based on fewer but better-characterized independent analytical
      techniques. The special advantages of IDMS for determination of S and Hg and for
      multi-element characterization of small-sample air particulate matter (SRM 2783)
      by IDMS and INAA are emphasized. Developments in materials production include the
      issuance of fresh-frozen biological materials and of jet-milled natural-matrix
      materials with improved homogeneity, including highly homogeneous air particulate
      matter and sediment SRMs for small-sample analytical techniques.

PMID- 17019588
TI  - Analgesics for pain after traumatic or orthopaedic surgery: what is the evidence-
      a systematic review.
AB  - OBJECTIVE: To assess analgesic drugs in the treatment of postoperative pain after
      traumatic and orthopaedic surgery (TOS). DESIGN: A systematic review of
      randomised clinical trials (RCTs). DATA SOURCES: Electronic PubMed, EMBASE, The
      Cochrane Library, and hand searches. STUDY SELECTION: RCTs of analgesics
      administered by oral, intramuscular, intravenous, subcutaneous or rectal route,
      were compared to other analgesics or placebo, in patients under TOS. Study
      design, characteristics of the study population, analgesic drugs tested, pain
      intensity and pain relief scores, and adverse effects were assessed. RESULTS:
      Ninety-two RCTs (9,596 patients) met our inclusion criteria. Forty-two (46%) were
      placebo-controlled, and 50 (54%) were direct comparisons between non-opioid,
      opioid, and/or combinations of both. Patients' mean age (SD) was 49 years (18).
      In most trials, gastrointestinal ulcer, liver and renal diseases were exclusion
      criteria. Only 30 trials (33%) were double-blind and reported standardised
      outcomes of pain intensity and pain relief; 19 of these were single-dose, and
      follow up of analgesic effects lasted no more than 12 h in 23 (77%). Globally,
      only nine trials (10%) were double blind, described dropouts or withdrawals,
      performed analysis by intention to treat, and reported the effects magnitude.
      CONCLUSION: Evidence from RCTs on the treatment of postoperative pain after TOS
      is inadequate for clinical decision making. Assessment of analgesics in pain
      after TOS should be based on agreed clinically relevant outcomes, in
      representative patients, and for longer observation periods. In addition, it
      should include direct comparisons between candidate drugs or their combinations
      and between various drug administration schedules.

PMID- 17019589
TI  - Ileoileal intussusception in children: ultrasonographic differentiation from
      ileocolic intussusception.
AB  - BACKGROUND: The treatment of ileoileal intussusception in children differs from
      that of ileocolic intussusception. OBJECTIVE: To differentiate ileoileal
      intussusception from ileocolic intussusception using ultrasonography. MATERIALS
      AND METHODS: We reviewed the clinical and ultrasonographic findings in 27
      patients with intussusception between September 2003 and July 2005. For
      statistical analysis the Mann-Whitney test was applied. RESULTS: Regarding
      ileoileal intussusceptions, 11 were documented in ten patients (seven boys, three
      girls; mean age 3.1 years). Symptoms suggestive of intussusception were present
      in nine patients. The mean diameter was 1.5 cm (range 1.1-2.5 cm) and length 2.5
      cm (range 1.5-6.0 cm). The intussusceptions were located in the paraumbilical
      region (n=6), the right upper quadrant (n=2), the right lower quadrant (n=2), and
      the left lower quadrant (n=1). Regarding ileocolic intussusceptions, 16 were
      documented in 14 patients (13 boys, 1 girl; mean age 1.9 years). All patients had
      symptoms suggestive of intussusception. The mean diameter was 3.7 cm (range 3.0
      5.5 cm) and mean length was 8.2 cm (range 5.0-12.5 cm). All intussusceptions were
      located in the right side of the abdomen. The difference in diameter and length
      between ileoileal and ileocolic intussusceptions was statistically significant
      (P<0.05). CONCLUSION: Unlike clinical symptoms, ultrasonography can differentiate
      between ileoileal and ileocolic intussusception. The diameter and length of the
      intussusception are the main criteria.

PMID- 17019590
TI  - MR imaging of transient synovitis: differentiation from septic arthritis.
AB  - BACKGROUND: Transient synovitis is the most common cause of acute hip pain in
      children. However, MR imaging findings in transient synovitis and the role of MR
      imaging in differentiating transient synovitis from septic arthritis have not
      been fully reported. OBJECTIVE: To describe the MR findings of transient
      synovitis and to determine whether the MR characteristics can differentiate this
      disease entity from septic arthritis. MATERIALS AND METHODS: Clinical findings
      and MR images of 49 patients with transient synovitis (male/female 36/13, mean
      age 6.1 years) and 18 patients with septic arthritis (male/female 10/8, mean age
      4.9 years) were retrospectively reviewed. RESULTS: MR findings of transient
      synovitis were symptomatic joint effusion, synovial enhancement, contralateral
      joint effusion, synovial thickening, and signal intensity (SI) alterations and
      enhancement in surrounding soft tissue. Among these, SI alterations and
      enhancement in bone marrow and soft tissue, contralateral joint effusion, and
      synovial thickening were statistically significant MR findings in differentiating
      transient synovitis from septic arthritis. CONCLUSIONS: The statistically
      significant MR findings in transient synovitis are contralateral (asymptomatic)
      joint effusions and the absence of SI abnormalities of the bone marrow. It is
      less common to have SI alterations and contrast enhancement of the soft tissues.
      The statistically significant MR findings in septic arthritis are SI alterations
      of the bone marrow, and SI alterations and contrast enhancement of the soft
      tissue. Ipsilateral effusion and synovial thickening and enhancement are present
      in both diseases.

PMID- 17019591
TI  - Viral ion channel proteins in model membranes: a comparative study by X-ray
      reflectivity.
AB  - We have investigated the effect of the transmembrane domain of three viral ion
      channel proteins on the lipid bilayer structure by X-ray reflectivity and
      scattering from oriented planar bilayers. The proteins show a similar effect on
      the lipid bilayer structural parameters: an increase in the lipid bilayer
      hydrophobic core, a decrease in the amplitude of the vertical density profile and
      a systematic change in the ordering of the acyl chains as a function of protein
      to-lipid ratio. These results are discussed in a comparative view.

PMID- 17019592
TI  - Gene delivery by cationic lipid vectors: overcoming cellular barriers.
AB  - Non-viral vectors such as cationic lipids are capable of delivering nucleic
      acids, including genes, siRNA or antisense RNA into cells, thus potentially
      resulting in their functional expression. These vectors are considered as an
      attractive alternative for virus-based delivery systems, which may suffer from
      immunological and mutational hazards. However, the efficiency of cationic
      mediated gene delivery, although often sufficient for cell biological purposes,
      runs seriously short from a therapeutics point of view, as realizing this
      objective requires a higher level of transfection than attained thus far. To
      develop strategies for improvement, there is not so much a need for novel
      delivery systems. Rather, better insight is needed into the mechanism of
      delivery, including lipoplex-cell surface interaction, route of internalization
      and concomitant escape of DNA/RNA into the cytosol, and transport into the
      nucleus. Current work indicates that a major obstacle involves the relative
      inefficient destabilization of membrane-bounded compartments in which lipoplexes
      reside after their internalization by the cell. Such an activity requires the
      capacity of lipoplexes of undergoing polymorphic transitions such as a membrane
      destabilizing hexagonal phase, while cellular components may aid in this process.
      A consequence of the latter notion is that for development of a novel generation
      of delivery devices, entry pathways have to be triggered by specific targeting to
      select delivery into intracellular compartments which are most susceptible to
      lipoplex-induced destabilization, thereby allowing the most efficient release of
      DNA, a minimal requirement for optimizing non-viral vector-mediated transfection.

PMID- 17019594
TI  - Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in
      obese insulin-resistant subjects.
AB  - AIMS/HYPOTHESIS: This study was designed to investigate the effect of short-term
      ACE inhibitor treatment on insulin sensitivity and to examine possible underlying
      metabolic and haemodynamic effects in obese insulin-resistant subjects. METHODS:
      A randomised, double-blind placebo-controlled trial was performed in 18 obese
      insulin-resistant men (age, 53 +/- 2 years; BMI, 32.6 +/- 0.8 kg/m(2);
      homeostasis model assessment of insulin resistance, 5.6 +/- 0.5; systolic blood
      pressure [SBP], 140.8 +/- 3.2; diastolic blood pressure [DBP], 88.8 +/- 1.6
      mmHg), who were free of any medication. The aim was to examine the effects of 2
      weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity,
      forearm blood flow, substrate fluxes across the forearm, whole-body substrate
      oxidation and intramuscular triacylglycerol (IMTG) content. RESULTS: Ramipril
      treatment decreased ACE activity compared with placebo (-22.0 +/- 1.7 vs 0.2 +/-
      1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood
      pressure (SBP, -10.8 +/- 2.1 vs -2.7 +/- 2.0 mmHg, respectively, p = 0.01; DBP, 
      10.1 +/- 1.3 vs -4.2 +/- 2.1 mmHg, respectively, p = 0.03). Ramipril treatment
      had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 +/-
      2.0, after: 19.1 +/- 2.4 micromol kg body weight(-1) min(-1), p = 0.44), insulin
      mediated glucose uptake across the forearm (before: 1.82 +/- 0.39, after: 1.92 +/
      0.29 micromol 100 ml forearm tissue(-1) min(-1), p = 0.81) and IMTG content
      (before: 45.4 +/- 18.8, after: 48.8 +/- 27.5 micromol/mg dry muscle, p = 0.92).
      Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood
      flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin
      stimulation were not significantly different between treatments.
      CONCLUSIONS/INTERPRETATION: Short-term ramipril treatment adequately reduced ACE
      activity and blood pressure, but had no significant effects on insulin
      sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body
      substrate oxidation and IMTG content in obese insulin-resistant subjects.

PMID- 17019596
TI  - Type 1 diabetes risk assessment: improvement by follow-up measurements in young
      islet autoantibody-positive relatives.
AB  - AIMS/HYPOTHESIS: Combinations of autoantibody characteristics, including antibody
      number, titre, subclass and epitope have been shown to stratify type 1 diabetes
      risk in islet autoantibody-positive relatives. The aim of this study was to
      determine whether autoantibody characteristics change over time, the nature of
      such changes, and their implications for the development of diabetes. METHODS:
      Five-hundred and thirteen follow-up samples from 141 islet autoantibody-positive
      first-degree relatives were tested for islet autoantibody titre, IgG subclass,
      and GAD and IA-2 antibody epitope. All samples were categorised according to four
      risk stratification models. Relatives had a median follow-up of 6.8 years and 48
      developed diabetes during follow-up. Survival analysis was used to determine the
      probability of change in risk category and of progression to diabetes. RESULTS:
      For each stratification model, the majority of relatives (71-81%) remained in the
      same risk category throughout follow-up. In the remainder, changes occurred both
      from lower to higher and from higher to lower risk categories. For all four
      models, relatives aged < 15 years were more likely to change risk category than
      those aged >15 years (0.001 < p < 0.03). Relatives whose autoantibody status
      changed from low- to high-risk categories had a higher risk of diabetes than
      relatives who remained in low-risk categories, and inclusion of autoantibody
      status during follow-up improved diabetes risk stratification in Cox proportional
      hazards models (p < 0.001). CONCLUSIONS/INTERPRETATION: Changes in islet
      autoantibodies are relevant to pathogenesis, and are likely to signal alterations
      in the disease process. Detection of changes through follow-up measurement will
      improve diabetes risk stratification, particularly in young individuals.

PMID- 17019597
TI  - Embryonic stem cell-based diabetes therapy--a long road to travel.

PMID- 17019595
TI  - Exercise training increases insulin-stimulated glucose disposal and GLUT4
      (SLC2A4) protein content in patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Exercise enhances insulin-stimulated glucose transport in
      skeletal muscle through changes in signal transduction and gene expression. The
      aim of this study was to assess the impact of acute and short-term exercise
      training on whole-body insulin-mediated glucose disposal and signal transduction
      along the canonical insulin signalling cascade. METHODS: A euglycaemic
      hyperinsulinaemic clamp, with vastus lateralis skeletal muscle biopsies, was
      performed at baseline and 16 h after an acute bout of exercise and short-term
      exercise training (7 days) in obese non-diabetic (n=7) and obese type 2 diabetic
      (n=8) subjects. RESULTS: Insulin-mediated glucose disposal was unchanged
      following acute exercise in both groups. Short-term exercise training increased
      insulin-mediated glucose disposal in obese type 2 diabetic (p<0.05), but not in
      obese non-diabetic subjects. Insulin activation of (1) IRS1, (2) IRS2, (3)
      phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the
      substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating
      protein important for GLUT4 (now known as solute carrier family 2 [facilitated
      glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute
      or chronic exercise in either group. GLUT4 protein content was increased in obese
      type 2 diabetic subjects (p<0.05), but not in obese non-diabetic subjects
      following chronic exercise. CONCLUSIONS/INTERPRETATION: Exercise training
      increased whole-body insulin-mediated glucose disposal in obese type 2 diabetic
      patients. These changes were independent of functional alterations in the insulin
      signalling cascade and related to increased GLUT4 protein content.

PMID- 17019598
TI  - Increased insulin secretory capacity but decreased insulin sensitivity after
      correction of iron overload by phlebotomy in hereditary haemochromatosis.
AB  - AIMS/HYPOTHESIS: We recently demonstrated that humans with hereditary
      haemochromatosis have decreased insulin secretory capacity with a compensatory
      increase in insulin sensitivity. We therefore determined how these measures
      change after correction of tissue iron overload. SUBJECTS AND METHODS: Five non
      diabetic subjects who had been studied previously at the time of initial
      diagnosis by means of the OGTT and frequently sampled intravenous glucose
      tolerance tests (FSIVGTT) underwent phlebotomy to normalise their serum ferritin.
      After normalisation of ferritin they were studied again (33+/-4 months after the
      initial studies) by OGTT and FSIVGTT. RESULTS: Normalisation of tissue iron
      stores resulted in an average 1.8-fold increase in the integrated area under the
      insulin curve during OGTT (p<0.0001), but no significant change in the area under
      the glucose curve (10% decrease, p=0.32). After phlebotomy, there was a 2.2-fold
      increase in insulin secretory capacity as determined by FSIVGTT (acute insulin
      response to glucose [AIRg], p<0.02) but a concomitant 70% fall in insulin
      sensitivity (Si, p<0.05). The disposition index (AIRgxSi) was unchanged (5%
      increase, p=0.90). BMI and fasting glucose were unchanged. At the time of
      diagnosis of haemochromatosis, four of the subjects had IGT. After normalisation
      of ferritin, two achieved NGT and two remained with IGT, despite 2.5- and 3.7
      fold increases in insulin secretory capacity. CONCLUSIONS/INTERPRETATION: Insulin
      secretory capacity improves after normalisation of iron stores in subjects with
      hereditary haemochromatosis. Glucose tolerance status improves incompletely
      because of decreased insulin sensitivity after phlebotomy. We conclude that
      tissue iron levels are an important determinant of insulin secretion and insulin
      action.

PMID- 17019599
TI  - Circulating concentrations of high-molecular-weight adiponectin are increased
      following Roux-en-Y gastric bypass surgery.
AB  - AIMS/HYPOTHESIS: In addition to weight loss, bariatric surgery for severe obesity
      dramatically alleviates insulin resistance. In this study, we investigated
      whether circulating concentrations of the high-molecular-weight (HMW) form of
      adiponectin are increased following gastric bypass surgery. The HMW form is
      implicated as the multimer responsible for adiponectin's hepatic insulin
      sensitising actions. SUBJECTS AND METHODS: We studied 19 women who were
      undergoing Roux-en-Y gastric bypass surgery. Studies were conducted prior to, and
      1 and 12 months after surgery. RESULTS: One month after surgery, total plasma
      adiponectin concentrations were unchanged. Nevertheless, increases in both HMW
      (by 40+/-15%, p=0.006) and the proportion of adiponectin in the HMW form (from
      40+/-2 to 50+/-2%, p<0.0001) were observed. At 12 months, total and HMW
      adiponectin concentrations were increased by 58+/-8% and 118+/-21%, respectively
      (both p<0.001). The majority (80%) of the increase of total adiponectin was due
      to an increase of the HMW form. After adjustment for covariates, increases of HMW
      and total adiponectin at 12 months were correlated with the decrease of fat mass
      (HMW, p=0.0076; total, p=0.0302). In subjects with improved insulin sensitivity
      at 12 months after surgery (n=18), the increase of HMW, but not that of total
      adiponectin, predicted the relative decrease of insulin resistance (HMW:
      p=0.0044; total: p=0.0775, after adjustment for covariates).
      CONCLUSIONS/INTERPRETATION: These data suggest that the reduction of fat mass
      following gastric bypass surgery is an important determinant of the increase of
      HMW adiponectin concentrations, which in turn is associated with and may
      contribute to the resulting improvement of insulin sensitivity.

PMID- 17019600
TI  - Coffee consumption and risk of total and cardiovascular mortality among patients
      with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Higher habitual coffee drinking has been associated with a lower
      risk of developing type 2 diabetes. The relation between coffee consumption and
      risk of cardiovascular disease (CVD) has been examined in many studies, but the
      issue remains controversial. This study was designed to assess the association
      between coffee consumption and CVD mortality among patients with type 2 diabetes.
      METHODS: We prospectively followed 3,837 randomly ascertained Finnish patients
      with type 2 diabetes aged 25 to 74 years. Coffee consumption and other study
      parameters were determined at baseline. The International Classification of
      Diseases was used to identify CHD, CVD and stroke cases using computerised record
      linkage to the national Death Registry. The associations between coffee
      consumption at baseline and risk of total, CVD, CHD, and stroke mortality were
      analysed by using Cox proportional hazards models. RESULTS: During the average
      follow-up of 20.8 years, 1,471 deaths were recorded, of which 909 were coded as
      CVD, 598 as CHD and 210 as stroke. The respective multivariate-adjusted hazard
      ratios in participants who drank 0-2, 3-4, 5-6, and > or =7 cups of coffee daily
      were 1.00, 0.77, 0.68 and 0.70 for total mortality (P<0.001 for trend), 1.00,
      0.79, 0.70 and 0.71 for CVD mortality (P=0.006 for trend), 1.00, 0.78, 0.70 and
      0.63 for CHD mortality (p=0.01 for trend), and 1.00, 0.77, 0.64 and 0.90 for
      stroke mortality (p=0.12 for trend). CONCLUSIONS/INTERPRETATION: In this large
      prospective study we found that in type 2 diabetic patients coffee drinking is
      associated with reduced total, CVD and CHD mortality.

PMID- 17019601
TI  - Prevalent and incident depression in community-dwelling elderly persons with
      diabetes mellitus: results from the ZARADEMP project.
AB  - AIMS/HYPOTHESIS: Although several studies have reported on the association
      between diabetes and depression, none have used both formal psychiatric criteria
      and a prospective, population-based design. Therefore, it remains unclear whether
      diabetes is a risk factor for the development of depression. Moreover, it is not
      clear if this effect is influenced by other chronic diseases and functional
      disabilities. METHODS: A large (n=4,803) representative community-based study in
      Spanish elderly subjects (at least 55 years of age) was conducted. The presence
      of major depression was assessed by means of a standardised psychiatric
      diagnostic interview (Automated Geriatric Examination for Computer Assisted
      Taxonomy). Subjects underwent a baseline assessment and a follow-up assessment
      after 2 and 5 years to determine the incidence of depression. RESULTS: At
      baseline 597 subjects (12.5%) were identified as having diabetes. Prevalence and
      incidence of depression in cases of diabetes were 15.4% and 16.5% respectively.
      Diabetes was associated with an increased risk of prevalent (odds ratio
      [OR]=1.47; 95% CI: 1.16-1.83) and incident (OR=1.40; 95% CI: 1.03-1.90)
      depression. Controlling for potential confounders did not essentially change
      these findings (prevalent depression: OR 1.41, 95% CI: 1.08-1.83; incident
      depression: OR 1.26, 95% CI: 0.90-1.77). CONCLUSIONS/INTERPRETATION: In a large,
      representative prospective population-based sample using strict psychiatric
      criteria, we confirmed previous findings that diabetes is associated with an
      increased risk of depression. The effect on the incidence of depression suggests
      that diabetes may play a role in the development of depression in the elderly.
      The presence of comorbid medical diseases seems to decrease the effects of
      diabetes on the risk of prevalent depression, but to increase the risk of
      incident depression.

PMID- 17019602
TI  - Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c
      are associated with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The sterol regulatory element-binding factor (SREBF)-1c is a
      transcription factor involved in the regulation of lipid and glucose metabolism.
      We have previously found evidence that a common SREBF1c single-nucleotide
      polymorphism (SNP), located between exons 18c and 19c, is associated with an
      increased risk of type 2 diabetes. The present study aimed to replicate our
      previously reported association in a larger case-control study and to examine an
      additional five SREBF1c SNPs for their association with diabetes risk and plasma
      glucose concentrations. METHODS: We genotyped six SREBF1c SNPs in two case
      control studies (n=1,938) and in a large cohort study (n=1,721) and tested for
      association with type 2 diabetes and with plasma glucose concentrations (fasting
      and 120-min post-glucose load), respectively. RESULTS: In the case-control
      studies, carriers of the minor allele of the previously reported SNP (rs11868035)
      had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04
      1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018),
      located in the 5' region, were significantly associated with diabetes risk (OR >
      or =1.21, p< or =0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the
      5' region were weakly (p<0.09) associated with plasma glucose concentrations in
      the cohort study. Rare homozygotes had increased (p< or =0.05) 120-min post-load
      glucose concentrations compared with carriers of the wild-type allele. Haplotype
      analyses showed significant (p=0.04) association with diabetes risk and confirmed
      the single SNP analyses. CONCLUSIONS/INTERPRETATION: In summary, we replicated
      our previous finding and found evidence for SNPs in the 5' region of the SREBF1c
      gene to be associated with the risk of type 2 diabetes and plasma glucose
      concentration.

PMID- 17019603
TI  - PARL Leu262Val is not associated with fasting insulin levels in UK populations.
AB  - AIMS/HYPOTHESIS: PARL, the gene encoding presenilins-associated rhomboid-like
      protein, maps to chromosome 3q27 within a quantitative trait locus that
      influences components of the metabolic syndrome. Recently, an amino acid
      substitution (Leu262Val, rs3732581) in PARL was associated with fasting plasma
      insulin levels in a US white population (N=1031). This variant was also found to
      modify the positive association between age and fasting insulin. The aim of this
      study was to test whether these findings could be replicated in two UK population
      based cohorts. METHODS: Participants from the Medical Research Council Ely and
      Hertfordshire cohort studies were genotyped for this variant using a SNaPshot
      primer extension assay and Taqman assay respectively. Full phenotypic and
      genotypic data were available for 3,666 study participants. RESULTS: Based on a
      dominant model, we found no association between the Leu262Val polymorphism and
      fasting insulin levels (p=0.79) or BMI (p=0.98). We did not observe the
      previously reported interaction between age and genotype on fasting insulin
      (p=0.14). CONCLUSIONS/INTERPRETATION: Despite having greater statistical power,
      our data do not support the previously reported association between PARL
      Leu262Val and fasting plasma insulin levels, a measure of insulin resistance. Our
      findings indicate that this variant is unlikely to be an important contributor to
      insulin resistance in UK populations.

PMID- 17019605
TI  - Salt-tolerant rhizobia isolated from a Tunisian oasis that are highly effective
      for symbiotic N2-fixation with Phaseolus vulgaris constitute a novel biovar (bv.
      mediterranense) of Sinorhizobium meliloti.
AB  - Nodulation of common bean was explored in six oases in the south of Tunisia.
      Nineteen isolates were characterized by PCR-RFLP of 16S rDNA. Three species of
      rhizobia were identified, Rhizobium etli, Rhizobium gallicum and Sinorhizobium
      meliloti. The diversity of the symbiotic genes was then assessed by PCR-RFLP of
      nodC and nifH genes. The majority of the symbiotic genotypes were conserved
      between oases and other soils of the north of the country. Sinorhizobia isolated
      from bean were then compared with isolates from Medicago truncatula plants grown
      in the oases soils. All the nodC types except for nodC type p that was specific
      to common bean isolates were shared by both hosts. The four isolates with nodC
      type p induced N(2)-fixing effective nodules on common bean but did not nodulate
      M. truncatula and Medicago sativa. The phylogenetic analysis of nifH and nodC
      genes showed that these isolates carry symbiotic genes different from those
      previously characterized among Medicago and bean symbionts, but closely related
      to those of S. fredii Spanish and Tunisian isolates effective in symbiosis with
      common bean but unable to nodulate soybean. The creation of a novel biovar shared
      by S. meliloti and S. fredii, bv. mediterranense, was proposed.

PMID- 17019604
TI  - Variants in the 5' region of the neuropeptide Y receptor Y2 gene (NPY2R) are
      associated with obesity in 5,971 white subjects.
AB  - AIMS/HYPOTHESIS: The gene encoding neuropeptide Y receptor Y2 (NPY2R) is widely
      expressed in the central nervous system, with particularly high abundance in the
      hypothalamus, which is known to be important for appetite regulation. We tested
      whether variations in NPY2R are associated with obesity. METHODS: The coding
      region of NPY2R was analysed for mutations in 48 obese Danish white subjects and
      two silent substitutions were identified: SNPs 1 and 2 (rs1047214 and rs2880415).
      SNP1 and additional reported variants (SNPs 3-6 [rs11099992, rs12649641,
      rs2342676 and rs6857530]) located in the 5' region were examined in 5,971 Danish
      white subjects. Since SNPs 1-2 and 4-6, respectively, were in tight linkage
      disequilibrium large-scale analyses of genetic epidemiology were restricted to
      SNPs 1, 3 and 4. RESULTS: Homozygous carriers of the minor A allele of SNP4 were
      more common among obese subjects; the AA frequency was 15.9 (95% CI 15.2-16.6)
      among 4,837 non-obese subjects (BMI <30 kg/m(2)) vs 19.0 (95% CI 17.2-20.8) among
      960 obese subjects (BMI > or =30 kg/m(2)), odds ratio 1.24 (95% CI 1.04-1.48),
      p=0.02. SNPs 1-3 were not associated with obesity. CONCLUSIONS/INTERPRETATION:
      Common variants rs12649641, rs2342676 and rs6857530 in the 5' region of NPY2R are
      associated with obesity in Danish white subjects.

PMID- 17019606
TI  - Identification of glycine betaine as compatible solute in Synechococcus sp.
      WH8102 and characterization of its N-methyltransferase genes involved in betaine
      synthesis.
AB  - Biosynthesis of glycine betaine from simple carbon sources as compatible solute
      is rare among aerobic heterotrophic eubacteria, and appears to be almost
      exclusive to the non-halophilic and slightly halophilic phototrophic
      cyanobacteria. Although Synechococcus sp. WH8102 (CCMP2370), a unicellular marine
      cyanobacterium, could grow up to additional 2.5% (w/v) NaCl in SN medium, natural
      abundance 13C nuclear magnetic resonance spectroscopy identified glycine betaine
      as its major compatible solute. Intracellular glycine betaine concentrations were
      dependent on the osmolarity of the growth medium over the range up to additional
      2% NaCl in SN medium, increasing from 6.8 +/- 1.5 to 62.3 +/- 5.5 mg/g dw. The
      ORFs SYNW1914 and SYNW1913 from Synechococcus sp. WH8102 were found as the
      homologous genes coding for glycine sarcosine N-methyltransferase and sarcosine
      dimethylglycine N-methyltransferase, heterologously over-expressed respectively
      as soluble fraction in Escherichia coli BL21(DE3)pLysS and purified by Ni-NTA His
      x bind resins. Their substrate specificities and the values of the kinetic
      parameters were determined by TLC and 1H NMR spectroscopy. RT-PCR analysis
      revealed that the two ORFs were both transcribed in cells of Synechococcus sp.
      WH8102 growing in SN medium without additional NaCl, which confirmed the pathway
      of de novo synthesizing betaine from glycine existing in these marine
      cyanobacteria.

PMID- 17019607
TI  - Children with congenital spastic hemiplegia obey Fitts' Law in a visually guided
      tapping task.
AB  - Fitts' Law is commonly found to apply to motor tasks involving precise aiming
      movements. Children with cerebral palsy (CP) have severe difficulties in such
      tasks and it is unknown whether they obey Fitts' Law despite their motor
      difficulties. If Fitts' Law still does apply to these children, this would
      indicate that this law is extremely robust and that even performance of children
      with damaged central nervous systems can adhere to it. The integrity of motor
      control processes in spastic CP is usually tested in complex motor tasks, making
      it difficult to determine whether poor performance is due to a motor output
      deficit or to problems related to cognitive processes since both affect movement
      precision. In the present study a simple task was designed to evaluate Fitts'
      Law. Tapping movements were evaluated in 22 children with congenital spastic
      hemiplegia (CSH) and 22 typically developing children. Targets (2.5 and 5 cm in
      width) were placed at distances of 10 and 20 cm from each other in order to
      provide Indices of Difficulty (ID) of 2-4 bits. Using this Fitts' aiming task,
      prolonged reaction and movement time (MT) were found in the affected hand under
      all conditions in children with CSH as compared to controls. Like in the control
      group, MT in children with CSH was related to ID. The intercept 'a',
      corresponding to the time required to realize a tapping movement, was higher in
      the affected hand of the children in the CSH group. Although, the slope b (which
      reflects the sensitivity of the motor system to a change in difficulty of the
      task) and the reciprocal of slope (that represents the cognitive information
      processing capacity, expressed in bits/s) were similar in both groups. In
      conclusion, children with CSH obey Fitts' Law despite very obvious limitations in
      fine motor control.

PMID- 17019608
TI  - Age-related differences in adaptation during childhood: the influences of
      muscular power production and segmental energy flow caused by muscles.
AB  - Acquisition of skillfulness is not only characterized by a task-appropriate
      application of muscular forces but also by the ability to adapt performance to
      changing task demands. Previous research suggests that there is a different
      developmental schedule for adaptation at the kinematic compared to the neuro
      muscular level. The purpose of this study was to determine how age-related
      differences in neuro-muscular organization affect the mechanical construction of
      pedaling at different levels of the task. By quantifying the flow of segmental
      energy caused by muscles, we determined the muscular synergies that construct the
      movement outcome across movement speeds. Younger children (5-7 years; n = 11),
      older children (8-10 years; n = 8), and adults (22-31 years; n = 8) rode a
      stationary ergometer at five discrete cadences (60, 75, 90, 105, and 120 rpm) at
      10% of their individually predicted peak power output. Using a forward dynamics
      simulation, we determined the muscular contributions to crank power, as well as
      muscular power delivered to the crank directly and indirectly (through energy
      absorption and transfer) during the downstroke and the upstroke of the crank
      cycle. We found significant age x cadence interactions for (1) peak muscular
      power at the hip joint [Wilks' Lambda = 0.441, F(8,42) = 2.65, p = 0.019]
      indicating that at high movement speeds children produced less peak power at the
      hip than adults, (2) muscular power delivered to the crank during the downstroke
      and the upstroke of the crank cycle [Wilks' Lambda = 0.399, F(8,42) = 3.07, p =
      0.009] indicating that children delivered a greater proportion of the power to
      the crank during the upstroke when compared to adults, (3) hip power contribution
      to limb power [Wilks' Lambda = 0.454, F(8,42) = 2.54, p = 0.023] indicating a
      cadence-dependence of age-related differences in the muscular synergy between hip
      extensors and plantarflexors. The results demonstrate that in spite of a
      successful performance, children construct the task of pedaling differently when
      compared to adults, especially when they are pushed to their performance limits.
      The weaker synergy between hip extensors and plantarflexors suggests that a lack
      of inter-muscular coordination, rather than muscular power production per se, is
      a factor that limits children's performance ranges.

PMID- 17019609
TI  - Optimization of nutrient parameters for lovastatin production by Monascus
      purpureus MTCC 369 under submerged fermentation using response surface
      methodology.
AB  - Lovastatin, an inhibitor of HMG-CoA reductase, was produced by submerged
      fermentation using Monascus purpureus MTCC 369. Five nutritional parameters
      screened using Plackett-Burman experimental design were optimized by Box-Behnken
      factorial design of response surface methodology for lovastatin production in
      shake flask cultures. Maximum lovastatin production of 351 mg/l were predicted in
      medium containing 29.59 g/l dextrose, 3.86 g/l NH4Cl, 1.73 g/l KH2PO4, 0.86 g/l
      MgSO4 x 7H2O, and 0.19 g/l MnSO4 x H2O using response surface plots and point
      prediction tool of DESIGN EXPERT 7.0 (Statease, USA) software.

PMID- 17019610
TI  - ST segment elevation in lead aVR during exercise testing is associated with LAD
      stenosis.
AB  - PURPOSE: To evaluate, in patients with chest pain, the diagnostic value of ST
      elevation (STE) in lead aVR during stress testing prior to (99m) Tc-sestamibi
      scanning correlating ischaemic territory with angiographic findings. METHODS:
      Consecutive patients attending for (99m) Tc-sestamibi myocardial perfusion
      imaging (MPI) completed a treadmill protocol. Peak exercise ECGs were coded. STE
      >or=0.05 mV in lead aVR was considered significant. Gated perfusion images and
      findings at angiography were assessed. RESULTS: STE in lead aVR occurred in 25%
      (138/557) of the patients. More patients with STE in aVR had a reversible defect
      on imaging compared with those who had no STE in aVR (41%, 56/138 vs 27%,
      114/419, p=0.003). Defects indicating a left anterior descending artery (LAD)
      culprit lesion were more common in the STE in aVR group (20%, 27/138 vs 9%,
      39/419, p=0.001). There was a trend towards coronary artery stenosis (>70%) in a
      double vessel distribution involving the LAD in those patients who had STE in aVR
      compared with those who did not (22%, 8/37 vs 5%, 4/77, p=0.06). Logistic
      regression analysis demonstrated that STE in aVR (OR 1.36, p=0.233) is not an
      independent predictor of inducible abnormality when adjusted for STD >0.1 mV (OR
      1.69, p=0.026). However, using anterior wall defect as an end-point, STE in aVR
      (OR 2.77, p=0.008) was a predictor even after adjustment for STD (OR 1.43,
      p=0.281). CONCLUSION: STE in lead aVR during exercise does not diagnose more
      inducible abnormalities than STD alone. However, unlike STD, which is not
      predictive of a territory of ischaemia, STE in aVR may indicate an anterior wall
      defect.

PMID- 17019611
TI  - The value of VEP in the diagnosis and post-operative monitoring of meningioma.
AB  - Meningiomas are the most frequently reported primary intracranial neoplasms. At
      first they usually cause unilateral visual loss but eventually result in a
      bilateral loss of vision. Depending upon the size and location of the tumour, the
      ocular signs and symptoms of meningiomas may include visual field abnormalities,
      optic atrophy, papilledema, diplopia and proptosis. This case report highlights
      the value of visual evoked potentials (VEP) in a patient with unexplained
      bilateral optic atrophy and a progressive loss of vision over 2 years. As a
      result of a delayed response in the VEP recorded from the right eye, a
      compressive lesion of the optic nerve was suspected. That prompted the referring
      ophthalmologist to request a MRI scan which led to the diagnosis of meningioma.
      Following the subtotal removal of the suprasellar meningioma, the remaining
      vision in the right eye improved and the latency of the VEP returned to the
      normal range. However, the VEP from the blind eye (left) did not show any
      measurable response either pre- or postoperatively. Experience with this patient
      suggests that early recognition of optic nerve compression is vital to an optimal
      outcome and the VEP technique, which is much more cost-effective than MRI, is
      clinically useful for detecting such compressive lesions.

PMID- 17019612
TI  - The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and
      functional evidence.
AB  - Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was
      recently found in the Chinese population from Singapore, and a common LRRK2
      missense variant, Gly2385Arg, was independently detected as a putative risk
      factor for PD in the Chinese population from Taiwan. To test the association
      between the Gly2385Arg variant in a large case-control sample of Chinese
      ethnicity from Singapore, and to perform functional studies of the wild type and
      Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving
      989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was
      higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1
      3.9, P = 0.014); these values yield an estimated population attributable risk
      (PAR) of approximately 4%. In a multivariate logistic regression analysis with
      the disease group (PD vs. controls) as the dependent variable and the genotype as
      an independent factor with adjustments made for the effect of age and gender, the
      heterozygous Gly2385Arg genotype remained associated with an increased risk of PD
      compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002).
      The glycine at position 2385 is a candidate site for N-myristoylation, and the
      Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic
      arginine, and increases the net positive charge of the LRRK2 WD40 domain. In
      transfection studies, we demonstrated that both the wild type and Gly2385Arg
      variant LRRK2 protein localize to the cytoplasm and form aggregates. However,
      under condition of oxidative stress, the Gly2385Arg variant was more toxic and
      associated with a higher rate of apoptosis. Our study lends support to the
      contention that the Gly2385Arg is a common risk factor for PD in the Chinese
      population. Our bioinformatics and in-vitro studies also suggest that the
      Gly2385Arg variant is biologically relevant and it might act through pro
      apoptotic mechanisms.

PMID- 17019615
TI  - Resident education and training in urogynecology and pelvic reconstructive
      surgery: a survey.
AB  - The aim of the study is to assess satisfaction with urogynecology education among
      obstetrics and gynecology residents. An Internet-based survey was designed to
      obtain a cross-sectional sample of third- and fourth-year residents. Didactic and
      surgical training as well as perceived surgical competency were assessed.
      Responses were received from 205 residents for this convenience sample. Nearly
      half (46%) of the respondents were unsatisfied with urogynecology resident
      education. There was no significant difference between respondents from academic
      programs and community programs with regard to overall satisfaction, the
      opportunity to work with the presence of a fellowship-trained urogynecologist or
      having a dedicated urogynecology rotation. Respondents were more satisfied with
      their education if they did a urogynecology rotation or worked with a fellowship
      trained urogynecologist. Female pelvic medicine and reconstructive surgery
      fellows were involved in the education of 23.9% of the respondents. Most
      respondents indicated comfort performing cystoscopy, anterior and posterior
      repairs, and McCall's culdoplasty following graduation. Overall, respondents
      indicated that residency training in urogynecology is less and later than
      desired, although they did feel competent at some urogynecologic surgeries.

PMID- 17019613
TI  - Pharmacological effect on pyeloureteric dynamics with a clinical perspective: a
      review of the literature.
AB  - We searched to review experimental and clinical trials concerning the
      capabilities of impacting on the ureteric and pelvic activity by means of
      pharmacological stimulation. Ureteropyeloscopy may cause high renal pelvic
      pressure. The normal pressure is in the range of 5-15 mmHg whereas pressure of
      410 mmHg has been measured during endoscopy. The threshold pressure for
      intrarenal reflux is about 35 mmHg. Studies in animals have revealed that high
      renal pelvic pressures may cause permanent damage to the renal parenchyma.
      Furthermore, it has been demonstrated that elevated pressures may entail an
      increased risk of several complications related to endourological procedures
      including bleeding, perforation and infection. In other words, means by which
      intrarenal pressure could be lowered during endourological procedures might be
      beneficial with respect to clinical outcomes. In vitro experiments support the
      existence of different receptors in the ureter and renal pelvis. The ureteric and
      pelvic responses to the corresponding neurotransmitters have been determined. It
      seems that alpha-adrenergic and cholinergic agents are stimulating whereas beta
      adrenergic agents inhibit ureteric activity. The effect may depend on the mode of
      administration. Drugs exerting advantageous effects in the pyeloureter may cause
      undesirable systemic side effects when administered intravenously. In animal
      studies, renal pelvic pressure can be significantly lowered by topical
      administration of beta-adrenergic agonists without systemic side effects. In vivo
      human studies are necessary to clarify the exact dose-response relationship and
      the degree of urothelial absorption of a drug before clinical use may be adopted.

PMID- 17019614
TI  - Molecular pathology of chondroid neoplasms: part 1, benign lesions.
AB  - This two-part review presents an overview of the molecular findings associated
      with both benign and malignant chondroid neoplasms. This first part presents a
      brief review of methods in molecular pathology along with a review of the
      cytogenetic and molecular genetic findings in benign chondroid neoplasms.
      Clinical aspects of the various lesions are briefly discussed, and each tumor is
      illustrated with representative radiographic and pathologic images. Malignant
      chondroid neoplasms will be considered in the second part of this review.

PMID- 17019616
TI  - Group differences in fairness perceptions and decision making in voting rights
      cases.
AB  - Participants recruited from one Historically Black University (HBU) and two
      predominantly White higher-education institutions evaluated and decided simulated
      voting rights case summaries in which the plaintiff was either a racially-defined
      (African American) or a nonracially-defined (farmers) minority group. Contrary to
      social identity and social justice findings of an in-group bias, the present
      study showed greater support at all institutions for the voting rights of the
      African Americans than for the rural farmers, and the greatest support for both
      minority groups was found at the HBU. Perceived evidence strength was a better
      predictor of decisions than perceived unfairness, and both of these predictor
      variables completely mediated the effects of institution-type and involvement of
      a racially-defined group on decisions.

PMID- 17019617
TI  - Youth psychopathy and criminal recidivism: a meta-analysis of the psychopathy
      checklist measures.
AB  - Although narrative reviews have suggested that "youth psychopathy" is a strong
      predictor of future crime and violence, to date no quantitative summaries of this
      literature have been conducted. We meta-analyzed recidivism data for the
      Psychopathy Checklist measures across 21 non-overlapping samples of male and
      female juvenile offenders. After removing outliers, psychopathy was significantly
      associated with general and violent recidivism (r (w)'s of .24 and .25,
      respectively), but negligibly related to sexual recidivism in the few studies
      examining this low base rate outcome. Even after eliminating outliers, however,
      considerable heterogeneity was noted among the effects, with some of this
      variability being explained by the gender and ethnic composition of the samples.
      Effect sizes for the small number of female samples available for analysis were
      mostly small and nonsignificant, and psychopathy was a weaker predictor of
      violent recidivism among more ethnically heterogeneous samples. In relation to
      predicting both general and violent recidivism, psychopathy performed comparably
      to an instrument designed specifically to assess risk, the Youth Level of
      Service/Case Management Inventory (Hoge & Andrews, 2002).

PMID- 17019618
TI  - Feature extraction for systolic heart murmur classification.
AB  - Heart murmurs are often the first signs of pathological changes of the heart
      valves, and they are usually found during auscultation in the primary health
      care. Distinguishing a pathological murmur from a physiological murmur is however
      difficult, why an "intelligent stethoscope" with decision support abilities would
      be of great value. Phonocardiographic signals were acquired from 36 patients with
      aortic valve stenosis, mitral insufficiency or physiological murmurs, and the
      data were analyzed with the aim to find a suitable feature subset for automatic
      classification of heart murmurs. Techniques such as Shannon energy, wavelets,
      fractal dimensions and recurrence quantification analysis were used to extract
      207 features. 157 of these features have not previously been used in heart murmur
      classification. A multi-domain subset consisting of 14, both old and new,
      features was derived using Pudil's sequential floating forward selection (SFFS)
      method. This subset was compared with several single domain feature sets. Using
      neural network classification, the selected multi-domain subset gave the best
      results; 86% correct classifications compared to 68% for the first runner-up. In
      conclusion, the derived feature set was superior to the comparative sets, and
      seems rather robust to noisy data.

PMID- 17019619
TI  - An anatomically based hybrid computational model of the human lung and its
      application to low frequency oscillatory mechanics.
AB  - Lung input impedance measured via forced oscillation over low frequency range has
      been confirmed as sensitive to the degree and the heterogeneity of lung disease.
      In this study we advanced an image-based, multi-scale computational model for the
      human lung, which includes upper and central airways, small airways and alveoli
      tissue unit. A three-dimensional (3-D) realistic model of the upper airway
      (reconstructed from MRI images) was combined with an anatomically based 3-D model
      of the central airways (based on MDCT images) to form a 3-D model of the large
      airways (from mouth to generation 6, incomplete for generations 4-6). The small
      airway trees distal to the central branches were based on a hypothetical airway
      tree for a normal healthy lung. A constant phase viscoelastic model was assumed
      for the alveolar tissue unit. Unsteady airflows in the large airways were
      simulated based on computational fluid dynamics (CFD). An experimentally measured
      broadband forcing flow was applied at the mouth. The impedance of the small
      airways was computed based on a one-dimensional transmission line model. The
      computed overall dynamic lung resistance and elastance compared very well with
      experimental values. Results showed that unsteady 3-D simulation and realistic
      geometry of the upper and large airways up to generations 4-6 can provide a
      reasonably accurate estimation of lung input impedance. The impedance of the
      upper airway constitutes a significant part of the total lung input impedance.
      The resistance of the upper airway accounts for 45-70% of the total lung
      resistance at frequencies between 0 and 1 Hz, and 70-81% at frequencies between 1
      and 8 Hz.

PMID- 17019620
TI  - Identification of (-)-beta-caryophyllene as a gender-specific terpene produced by
      the multicolored Asian lady beetle.
AB  - This work reports the development and use of techniques for characterizing
      volatile chemicals emitted by the multicolored Asian lady beetle, Harmonia
      axyridis (Pallas) (Coleoptera: Coccinellidae), in an effort to identify the
      semiochemicals involved in establishment and persistence of overwintering beetle
      aggregations. Volatiles emitted from live beetles were detected by using whole
      air sampling and solid-phase microextraction (SPME). Adsorbed volatiles were
      thermally desorbed and identified with gas chromatography-mass spectrometry
      (GC/MS). By comparing the chromatograms of volatiles emitted from live male and
      female beetles, a sesquiterpene, (-)-beta-caryophyllene, was found only in the
      females. The identity of (-)-beta-caryophyllene was confirmed by using NIST
      Library searches, comparing retention times with those of known standards, and by
      using higher-resolution GC/MS above bench top capability. Although SPME trapping
      detected a wider array of compounds compared to whole-air sampling, the latter
      method is better suited for automation. Unattended automated sampling is required
      for the continuous measurement of targeted compounds under dynamically changing
      incubation conditions. These conditions, mimicking natural overwintering
      conditions, are essential to our long-term goal of using this technology to
      detect and identify the aggregation pheromone of H. axyridis.

PMID- 17019621
TI  - Ellagitannins have greater oxidative activities than condensed tannins and
      galloyl glucoses at high pH: potential impact on caterpillars.
AB  - Plants synthesize a diversity of tannin structures but little is known about
      whether these different types have different oxidative activities in herbivores.
      Oxidative activities of hydrolyzable and condensed tannins were compared at pH 10
      with two methods: EPR spectrometry was used to quantify semiquinone radicals in
      anoxic conditions and a spectrophotometric assay was used to measure the rate of
      browning of phenolics oxidized in ambient oxygen conditions. A little-studied
      group of hydrolyzable tannins (ellagitannins) contained the most active tannins
      examined, forming high concentrations of semiquinone radicals and browning at the
      highest rates. On average, galloyl glucoses and high-molecular-weight
      gallotannins had intermediate to low oxidative activities. Condensed tannins
      generally formed low levels of semiquinone radicals and browned most slowly. The
      results suggest that ellagitannin-rich plants have active oxidative defenses
      against herbivores, such as caterpillars, whereas the opposite may hold true for
      plants that contain predominantly condensed tannins or high-molecular-weight
      gallotannins.

PMID- 17019622
TI  - Differentiation of competitive vs. non-competitive mechanisms mediating
      disruption of moth sexual communication by point sources of sex pheromone (part
      2): Case studies.
AB  - Eleven out of 13 disruption profiles (plots of dispenser density vs. male catch)
      from moth sex pheromone literature were consistent with a competitive-attraction
      mechanism, in which dispensers attract males and thereby divert them from
      females. Mean dispenser activity (D(a)) across all competitive-attraction cases
      was 0.04 +/- 0.06 (SD); values ranged from 0.0005 for a tiny laminated flake
      dispenser of racemic disparlure targeting gypsy moth to 0.2 for polyethylene tube
      dispensers used against lightbrown apple moth. A dispenser application activity
      (D(Aa)) can be calculated by multiplying D(a) by the number of such dispensers
      applied per hectare of crop. The highest dispenser application activity (D(Aa))
      values approached 200 and corresponded to >99% inhibition of catches of male
      moths in monitoring traps. Relative to the D(Aa) scale, % inhibition of catches
      of male moths compressed and obscured large differences in D(Aa) when %
      disruption exceeded 90%. For cases of competitive attraction, these two efficacy
      scales can be interconverted by using the formula: D(Aa) approximately = 100/(100
      minus % disruption). When disruptive point sources of pheromone were directly
      observed, male moths were seen approaching pheromone dispensers whose disruption
      profiles matched competitive attraction. Two cases fit non-competitive disruption
      mechanisms, which include camouflage, desensitization (adaptation and/or
      habituation), and sensory imbalance. In these cases, pheromone was released at
      rates higher than for cases of disruption by competitive attraction. Practical
      ramifications of the finding that competitive attraction appears to be the
      prevalent mechanism for moth mating disruption by pheromone point sources are
      listed. We believe that the congruence of diverse sets of mating disruption field
      data with explicit a priori predictions validates competitive-attraction theory.
      The analytical tools and principles governing competitive attraction that were
      uncovered during this study of mating disruption of moths should be generally
      applicable to competitive-attraction phenomena.

PMID- 17019623
TI  - Differentiation of competitive vs. non-competitive mechanisms mediating
      disruption of moth sexual communication by point sources of sex pheromone (part
      I): Theory.
AB  - This study establishes a theoretical framework for differentiating among possible
      behavioral mechanisms whereby sexual communication of moths is disrupted in crops
      treated with point sources of pheromone. The major mechanisms recognized in the
      mating disruption literature fall into two main categories: competitive
      (competitive attraction = false-plume-following) and non-competitive (camouflage,
      desensitization, and sensory imbalance). Each disruption mechanism has been
      precisely defined verbally, and then the distinguishing characteristics of the
      two categories were defined mathematically. The sets of predictions associated
      with each category were visualized by graphical plots of mathematical
      simulations. Profiles of simulated male visitation rates to pheromone-baited
      traps deployed in pheromone-treated crops were graphed against density of
      pheromone dispensers by using various types of axes. Key traits of non
      competitive attraction are as follows: concave profiles on untransformed axes,
      with an asymptotic approach to zero catch of male moths in traps; a straight line
      with positive slope when 1/catch is plotted against dispenser density (Miller-Gut
      plot); and a straight line with negative slope when catch is plotted against
      dispenser density * catch (Miller-de Lame plot). Key traits of non-competitive
      disruption profiles include: an initial linear disruption profile on
      untransformed axes; a concave Miller-Gut plot; and a recurving Miller-de Lame
      plot. These differences in profiles provide a basis for distinguishing
      competitive from non-competitive mechanisms when analyzing disruption profiles
      from field experiments. Slopes and intercepts of these secondary plots can also
      reveal both male and female moth densities, if the relative attractiveness of
      traps, females, and dispensers is known. The absolute value of the slope of the
      Miller-de Lame plot is a measure of each dispenser's activity (D(a)) for
      suppressing catch of male moths in traps. An application activity (D(Aa)) for a
      given dispenser can be calculated by multiplying D(a) by the number of such
      dispensers applied per hectare of crop.

PMID- 17019624
TI  - Risperidone improves behavioral symptoms in children with autism in a randomized,
      double-blind, placebo-controlled trial.
AB  - Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week,
      double-blind, placebo-controlled trial of risperidone for pervasive developmental
      disorders. The primary efficacy measure was the Aberrant Behavior Checklist
      Irritability (ABC-I) subscale. Data were available for 55 children given
      risperidone (n=27) or placebo (n=28); mean baseline ABC-I ( +/- SD) was 20.6
      (8.1) and 21.6 (10.2). Risperidone [mean dose ( +/- SD): 1.37 mg/day (0.7)]
      resulted in significantly greater reduction from baseline to endpoint in ABC-I
      versus placebo [mean change ( +/- SD): -13.4 (1.5) vs. -7.2 (1.4), P<0.05; ES=
      0.7]. The most common adverse effect with risperidone was somnolence (74% vs. 7%
      with placebo). Risperidone treatment was well tolerated and significantly
      improved behavioral problems associated with autism.

PMID- 17019625
TI  - Parent report of stereotyped behaviors, social interaction, and developmental
      disturbances in individuals with Angelman syndrome.
AB  - Research examining autistic symptoms in Angelman syndrome (AS) is limited. The
      goal of this study was to further characterize the nature of stereotyped
      behaviors, social interaction deficits, and developmental disturbances in
      individuals with AS. Parents of 248 individuals between the ages of 3 and 22
      completed a survey of autistic symptomatology by mail, the Gilliam Autism Rating
      Scale. Results confirmed a high degree of developmental delay and limited
      expressive language skills. In terms of stereotyped behaviors and social
      interaction, areas of convergence and divergence between AS and behaviors
      typically associated with autism spectrum disorders are described. The
      relationship between child characteristics (age, gender, seizure disorder,
      genetic subtype) and autistic symptomatology are discussed.

PMID- 17019627
TI  - DTkid: interactive simulation software for training tutors of children with
      autism.
AB  - Discrete-trial training (DTT) relies critically on implementation by trained
      tutors. We report three experiments carried out in the development of "DTkid"-
      interactive computer simulation software that presents "SIMon", a realistic
      virtual child with whom novice tutors can learn and practise DTT techniques.
      Experiments 1 and 2 exposed groups of participants either to DTkid training or to
      a control task. Participants in the former groups demonstrated significantly
      greater procedural and declarative knowledge of DTT. Experiment 3 confirmed this
      finding, further demonstrating that observation of DTkid training trials alone
      was sufficient to enhance participants' declarative and procedural knowledge of
      DTT. Results indicate that DTkid offers the potential for an effective means of
      teaching DTT skills to novice tutors of children with autism.

PMID- 17019626
TI  - [3H]-flunitrazepam-labeled benzodiazepine binding sites in the hippocampal
      formation in autism: a multiple concentration autoradiographic study.
AB  - Increasing evidence indicates that the GABAergic system in cerebellar and limbic
      structures is affected in autism. We extended our previous study that found
      reduced [(3)H]flunitrazepam-labeled benzodiazepine sites in the autistic
      hippocampus to determine whether this reduction was due to a decrease in binding
      site number (B (max)) or altered affinity (K (d)) to bind to the ligand.
      Quantitation of hippocampal lamina demonstrated a 20% reduction in B (max)
      indicating a trend toward a decreased number of benzodiazepine binding sites in
      the autistic group but normal K (d) values. A reduction in the number of
      hippocampal benzodiazepine binding sites suggests alterations in the modulation
      of GABA(A) receptors in the presence of GABA in the autistic brain, possibly
      resulting in altered inhibitory functioning of hippocampal circuitry.

PMID- 17019628
TI  - Acculturation and aggression in Latino adolescents: a structural model focusing
      on cultural risk factors and assets.
AB  - The specific aim of this investigation was to map cultural factors associated
      with aggressive behavior in Latino adolescents. Interviews were conducted with a
      sample of 481 foreign- and U.S.-born Latino adolescents living in North Carolina
      and Arizona. Structural Equation Modeling was used to validate a conceptual model
      linking adolescent and parent culture-of-origin and U.S. cultural involvement,
      acculturation conflicts, and perceived discrimination to family processes
      (familism and parent-adolescent conflict) and adolescent aggression. Parent
      adolescent conflict was the strongest cultural risk factor followed by perceived
      discrimination. Familism and adolescent culture-of-origin involvement were key
      cultural assets associated with less aggressive behavior. Exploratory mediation
      analyses suggested that familism and parent-adolescent conflict mediated the
      effects of acculturation conflicts, parent and adolescent culture-of-origin
      involvement, and parent U.S. cultural involvement on adolescent aggression.
      Implications for prevention programming were discussed.

PMID- 17019629
TI  - Reactivity of tic observation procedures to situation and setting.
AB  - Tic frequency was assessed and compared across home and clinic as well as three
      experimentally-manipulated situations in order to assess the phenomenon of tic
      reactivity. Forty-three youngsters with chronic tic disorder recruited from two
      geographically-distinct sites were videotaped over three weekly laboratory visits
      under each of the following conditions: (1) alone/camera present, (2) other
      present/camera present, and (3) alone/camera hidden. Contrary to expectation,
      more tics were observed during overt as compared to covert observation, while the
      presence of another person had no overall impact on tic expression. Mean tic
      counts obtained from clinic observation did not significantly differ from those
      obtained at home collected either one day before or after. Tic frequency counts
      were remarkably stable over the three weekly assessments both at home and clinic.
      Study findings are consistent with past observations that tic expression can be
      influenced by environmental factors and suggest the stability of tic frequency
      may exhibit greater temporal and setting stability than previously thought. The
      clinical and research implications of these results are discussed.

PMID- 17019630
TI  - Patterns of aberrant eating among pre-adolescent children in foster care.
AB  - The paper reports epidemiological and phenomenological investigations of aberrant
      eating among 347 pre-adolescent children in court-ordered foster and kinship
      care, in New South Wales, Australia. A quarter of children displayed clinically
      significant aberrant eating problems, with no evidence of gender or age effects.
      Two distinct patterns were identified. The first is a pattern of excessive eating
      and food acquisition and maintenance behaviors without concurrent obesity (termed
      Food maintenance syndrome), resembling the behavioral correlates of Hyperphagic
      Short Stature (Psychosocial Dwarfism). Various data suggest this pattern is
      primarily triggered by acute stress, including maltreatment in care, against a
      background of complex psychopathology and developmental disabilities. The second
      is a cluster of pica-type eating behaviors that correlates with self-injurious
      behavior, and is closely associated with developmental disabilities. The paper
      includes recommendations for clinicians working with pre-adolescent children in
      care.

PMID- 17019631
TI  - Donation of surplus frozen embryos for stem cell research or fertility treatment
      should medical professionals and healthcare institutions be allowed to exercise
      undue influence on the informed decision of their former patients?
AB  - The increasing availability of clinical assisted reproduction has led to an
      accumulated surplus of frozen embryos within fertility clinics worldwide. Couples
      that have attained success in clinical assisted reproduction, and have no further
      desire to reproduce; are often faced with an agonizing dilemma on what to do with
      their surplus frozen embryos-whether to simply discard them, or donate either for
      scientific research or to other infertile couples. There is a risk that persons
      or institutions directly involved in procuring donated embryos will prioritize
      their own interests over the informed choice of the patient to donate either for
      scientific research or to other infertile couples. Very often, formerly infertile
      couples who have attained reproductive success feel an overwhelming sense of
      gratitude to the fertility doctor handling their treatment. Hence, there is a
      risk of medical professionals exercising undue influence on their former
      patients, to sway the final decision to their preferred outcome. In the private
      practice setting, the preferred outcome would likely be donation for the
      treatment of other infertile couples; whilst in the case of medical professionals
      affiliated with research or academic institutions, the preferred outcome would
      likely be donation for stem cell research.

PMID- 17019633
TI  - Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review
      and meta-analysis.
AB  - PURPOSE: To assess the effects of sperm DNA damage, as determined by the TUNEL
      assay and the SCSA respectively, on the outcomes of IVF/ICSI treatment. METHODS:
      A Medline search (from Jan 1978 to Apr 2006) was performed, together with a
      manual search of the bibliographies of retrieved original papers and review
      articles. 8 articles met all inclusion/exclusion criteria, of which, 5 used the
      TUNEL assay and the other 3 used the SCSA. All these articles were included in
      separate meta-analysis. The meta-analysis was conducted using the RevMan software
      with fixed-effect model or random-effects model. RESULTS: As for articles using
      the TUNEL assay, the pooled results of IVF outcomes indicated that the clinical
      pregnancy rate (RR 0.68, 95% CI 0.54 to 0.85, P = 0.006), but not the
      fertilization rate (RR 0.79, 95% CI 0.54 to 1.16, P = 0.23) decreased
      significantly for patients with high degree of sperm DNA damage compared with
      those with low degree of sperm DNA damage. RRs of the ICSI outcomes indicated
      that there was no significant difference in either fertilization rate (RR 1.03,
      95% CI 0.89 to1.18, P = 0.70) or clinical pregnancy rate (RR 0.76, 95% CI 0.55 to
      1.04, P = 0.09) between these two groups. As for the SCSA papers, the pooled
      results showed no significant effects of sperm DNA damage on the clinical
      pregnancy rate after IVF (RR 0.58, 95% CI 0.25 to 1.31, P = 0.19) or ICSI (RR
      1.18, 95% CI 0.81 to 1.74, P = 0.38). CONCLUSION(S): Our meta-analysis indicates
      that sperm DNA damage, as assessed by the TUNEL assay, significantly decreases
      only the chance of IVF clinical pregnancy, but not that of either IVF
      fertilization or ICSI fertilization or ICSI clinical pregnancy. Besides, our
      results also reveal that sperm DNA damage, when assessed by the SCSA, has no
      significant effect on the chance of clinical pregnancy after IVF or ICSI
      treatment.

PMID- 17019632
TI  - Distribution of persistent organochlorine contaminants in infertile patients from
      Tanzania and Germany.
AB  - PURPOSE: To test whether environmental pollutants could affect fertility in
      humans. METHODS: 31 women and 16 men from Tanzania and 21 couples from Germany
      were included (n = 89). Pesticides and polychlorinated biphenyls were measured in
      serum, follicular fluid or seminal plasma by gaschromatography and related to
      sperm quality and pregnancy rates. RESULTS: Higher concentrations of DDT+DDE and
      dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were
      detected. All compounds showed higher concentrations in serum and lowest
      concentrations in seminal plasma. A lower pregnancy rate in German women with
      high serum concentrations of DDT+DDE was observed. The toxins had no impact on
      sperm quality. CONCLUSIONS: The distribution of toxins between agricultural and
      industrial countries is different. Seminal plasma seems to be inert against
      chemicals. In patients with high serum concentrations of DDT and DDE pregnancy
      rates were impaired.

PMID- 17019634
TI  - A preliminary panorama of the diversity of N1 subtype influenza viruses.
AB  - N1 subtype influenza viruses have caused many epidemics and even a few pandemics
      in humans, pigs and fowls including 1918 human H1N1 pandemic, which killed 20-50
      million people and the current avian H5N1 pandemic in the Eastern Hemisphere,
      which has caused great economic losses and posed a severe threat to human public
      health. To elucidate the whole diversity of N1 influenza viruses from a dynamic
      view, 202 neuraminidase (NA) sequences of N1 subtype influenza isolates were
      selected and analyzed in this study. Our results showed that N1 influenza
      isolates could be divided into three distinct lineages (Human, Classic Swine and
      Avian), which largely circulated in the humans, pigs and fowls respectively,
      though viruses in the Avian lineage could infect mammals and even there was a
      sublineage in the Avian lineage wholly isolated from pigs. The Avian lineage and
      the Human lineage, which have existed at least for decades, possibly began
      divergence around in 1890 through regression analysis. Both of the Human and
      Avian lineages could be further divided into some sublineages, and the
      correlation between these lineages (or sublineages) and their isolation places,
      isolation time, hemagglutinin (HA) subtypes, host species, virulence, or
      epidemics were discussed. The panorama of the diversity of N1 influenza viruses
      presented in this study provided a framework for the studies on the evolution and
      epidemiology of N1 influenza viruses.

PMID- 17019635
TI  - Spherical splines and average referencing in scalp electroencephalography.
AB  - EEG analysis and interpretation are affected by the reference electrode. Average
      referenced potentials are used widely to approximate the potentials relative to
      infinity, but estimates of the average surface potential are prone to errors due
      to incomplete sampling of the scalp surface. Even if the electrode density is
      high, this arises by not sampling the inferior scalp surface. This paper shows
      analytically how the spherical splines represent the average surface potential.
      It also shows that, for spline orders m > or = 3, the interpolating function is
      well approximated by its large-m limit, weighting near and distant electrodes
      with opposite signs. Together these motivate the hypothesis that spherical
      splines permit a better estimate of the potentials relative to infinity than the
      discrete average computed over superior scalp electrodes. It tests this
      hypothesis using numerical simulations in a four-sphere head model with single-
      and many-dipole sources, and variations in spline order, electrode number and
      head model parameters. The results confirm that the spherical splines yield a
      better estimate of the potentials relative to infinity, provided the electrode
      sampling density is adequate.

PMID- 17019636
TI  - Long-term single procedure efficacy of catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Two important limitations of the data regarding the outcomes of
      catheter ablation of atrial fibrillation (AF) are the short-term follow-up used
      in most published studies and the lack of single-procedure outcomes. OBJECTIVE:
      The objective was to report the long-term single-procedure outcomes at our
      center. MATERIALS AND METHODS: The patient population was comprised of 200
      consecutive patients who underwent ablation (133 men; age 56 +/- 11 years).
      Atrial fibrillation was paroxysmal in 92 (46%). Success was defined as absence of
      symptomatic AF, off antiarrhythmic drug (AAD) after a single procedure. RESULTS:
      After a follow-up of 26 +/- 11 months, the single-procedure long-term success
      rate was 28% with an additional 7% of patients demonstrating improvement. After
      including repeat procedures in 64 patients, the overall long-term success rate
      was 41% with 11% demonstrating improvement. Further subgroup analysis of 48
      paroxysmal AF patients considered to be optimal candidates for the procedure,
      revealed a long-term success rate of 69% with an additional 4% demonstrating
      improvement. A major complication occurred in 7.9% of patients. CONCLUSION: The
      results reveal that the long-term single-procedure success rate of catheter
      ablation of AF in a cohort of patients with predominantly non-paroxysmal AF is
      less than 40%. The inclusion of redo procedures resulted in an improvement in
      outcomes. A much higher success rate of 69% was achieved in patients with
      paroxysmal AF considered to be optimal candidates for this procedure. These
      results make it clear that further advances in the technique of catheter ablation
      of AF are needed to improve the safety and efficacy of this procedure. In order
      to be able to compare outcomes of various techniques in differing patient
      populations, we urge investigators to report long-term single procedure outcomes.

PMID- 17019637
TI  - Optimal target temperature for slow pathway ablation in patients with
      atrioventricular nodal reentrant tachycardia.
AB  - OBJECTIVE: To define optimal target temperature for the slow pathway ablation.
      MATERIALS AND METHODS: In this study, 268 patients with atrioventricular nodal
      reentrant tachycardia (190 females; mean age, 49 +/- 14 years) who underwent slow
      pathway ablation using a combined electroanatomic approach were enrolled. The
      patients were categorized into Group 1 if target temperature was < 55 degrees C
      or into Group 2 if target temperature was > or = 55 degrees C. Group 2 was
      divided into three subgroups of 55 degrees C (Sgp-1), 60 degrees C (Sgp-2), and
      65 degrees C (Sgp-3). RESULTS: Acute success rate was similar in both groups (P =
      0.83). The ablation time (26.2 +/- 20 vs. 36.5 +/- 28 min; P = 0.014),
      fluoroscopy time (11.6 +/- 9.7 vs. 17.8 +/- 16.6 min; P = 0.035), and number of
      applications (4.1 +/- 3.2 vs. 9.1 +/- 6.5; P = 0.02) were lower for Group 2 than
      Group 1 patients. The frequency of AV or VA block, impedance rise, and coagulum
      formation were comparable in two groups (all P > 0.05). During mean follow-up of
      14 +/- 3 months, recurrence of the arrhythmia was seen in higher proportion of
      Group 1 than Group 2 patients (P = 0.036). Among the Group 2 patients, there were
      no significant differences between the three subgroups in terms of acute success
      rate, fluoroscopy time, risks of AV and VA block, pericardial effusion, and
      recurrence (All P > 0.05). Number of applications and RF pulse duration were
      lower in Sgp-2 and 3 compared to Sgp-1 (All P > 0.05). Impedance rise and
      coagulum formation were slightly higher in Sgp-3 compared to Sgp-1 and 2 but this
      difference did not reach statistical significance (All P > 0.05). CONCLUSIONS:
      Compared to less than 55 degrees C, target temperatures > or = 55 degrees C
      during slow pathway ablation significantly reduces fluoroscopy time, RF pulse
      duration, number of RF applications, and recurrence of AVNRT without increase in
      risk of AV or VA block or coagulum formation.

PMID- 17019639
TI  - Unusual Wenckebach phenomenon due to an atrial tachycardia arising from the apex
      of Koch's triangle in the presence of dual AV nodal physiology.
AB  - A case of a patient with narrow QRS tachycardia and without structural heart
      disease is presented. The electrophysiologic study revealed an atrial tachycardia
      in the presence of dual atrioventricular (AV) nodal physiology and AV block at
      suprahisian level, the latter two leading to an unusual Wenckebach periodicity.
      The entire septal area was mapped as was the coronary sinus (CS) os and the
      earliest atrial activation was found at the apex of Koch's triangle in close
      vicinity to the His bundle (HB). Cryomapping at that point reproducibly
      terminated the tachycardia without impairing AV conduction. Cryoablation rendered
      the tachycardia non-inducible. Discontinuous AV conduction persisted but AV nodal
      reentrant tachycardia (AVNRT) was not inducible. Six months later the patient is
      arrhythmia-free.

PMID- 17019638
TI  - Psychological indices and phantom shocks in patients with ICD.
AB  - INTRODUCTION: Some patients with ICDs experience the sensation of a shock in the
      absence of true therapy (phantom shock). We hypothesize that phantom shocks may
      be a manifestation of anxiety, depression or PTSD. METHODS AND RESULTS: All
      patients over 18 years old with an ICD were eligible to enroll in the study. The
      first 75 subjects who agreed to participate were enrolled and divided into three
      groups: ICD patients with phantom shocks (n = 19); ICD patients who had actual
      shocks (n = 28) and ICD patients who had no shocks (n = 28). During a clinic
      visit a demographic questionnaire and three psychological rating scales were
      administered: the Spielberger State-Trait Anxiety Inventory (STAI); the Center
      for Epidemiologic Studies Depression Scale (CES-D) and the Posttraumatic Stress
      Checklist (PCL-C). No significant differences between groups were found in
      gender, race, age, history of MI or cardiac surgery status. Data analysis of the
      psychological indices using one-way ANOVA showed that the group with phantom
      shocks had more depression (CES-D p = 0.011) and more anxiety (STAI p = 0.010)
      than the other groups. Multiple comparisons of group means showed a greater
      percentage of clinically depressed patients in the phantom shock group than in
      the other groups. CONCLUSION: Patients with phantom shocks are more likely to be
      clinically depressed and have higher levels of anxiety than other ICD patients,
      regardless of history of actual shocks.

PMID- 17019640
TI  - Low right atrial tachycardia with positive P waves in the inferior leads:
      explanation by electroanatomical mapping.
AB  - The P-wave morphology can help trying to localize the origin of an ectopic atrial
      tachycardia noninvasively. We describe the case of a 54-year-old male patient
      with an ectopic right atrial tachycardia and positive P waves in the inferior
      leads on a 12 lead ECG. Electroanatomical mapping with the CARTO system localized
      the focus at the low right atrial free wall. With that origin and a very slow
      conduction through the cavotricuspid isthmus the activation spread clockwise
      around the tricuspid anulus and resulted in a craniocaudal septal activation
      pattern, which subsequently caused a positive P-wave morphology in the inferior
      leads.

PMID- 17019641
TI  - Common ostium of the inferior pulmonary veins in a patient undergoing left atrial
      ablation for atrial fibrillation.

PMID- 17019642
TI  - General method of preparation of uniformly 13C, 15N-labeled DNA fragments for NMR
      analysis of DNA structures.
AB  - (13)C, (15)N labeling of biomolecules allows easier assignments of NMR resonances
      and provides a larger number of NMR parameters, which greatly improves the
      quality of DNA structures. However, there is no general DNA-labeling procedure,
      like those employed for proteins and RNAs. Here, we describe a general and widely
      applicable approach designed for preparation of isotopically labeled DNA
      fragments that can be used for NMR studies. The procedure is based on the PCR
      amplification of oligonucleotides in the presence of labeled deoxynucleotides
      triphosphates. It allows great flexibility thanks to insertion of a short DNA
      sequence (linker) between two repeats of DNA sequence to study. Size and sequence
      of the linker are designed as to create restriction sites at the junctions with
      DNA of interest. DNA duplex with desired sequence and size is released upon
      enzymatic digestion of the PCR product. The suitability of the procedure is
      validated through the preparation of two biological relevant DNA fragments.

PMID- 17019643
TI  - Isolation of extremely AT-rich genomic DNA and analysis of genes encoding
      carbohydrate-degrading enzymes from Orpinomyces sp. strain PC-2.
AB  - An effective method for extraction of intact genomic DNA from the extremely AT
      rich polycentric anaerobic fungus Orpinomyces sp. strain PC-2 has been developed.
      This procedure involves removal of glycogen-like storage polysaccharides using
      hexadecyltrimethylammonium bromide (CTAB) and high salt washes. The DNA was
      digested with various restriction enzymes and was suitable for use as a PCR
      template, for Southern blotting, and for genomic library construction. Genomic
      DNA analysis of three representative genes (celE, bgl1, and xynA) encoding (hemi
      ) cellulolytic enzymes of the fungus revealed multiplicity of family 5
      endocellulase genes (celE-like), and family 1 beta-glucosidase genes (bgl1-like),
      but only a single copy of family 11 xylanase gene (xynA).

PMID- 17019644
TI  - Plasmid-related resistance to cefoxitin in species of the Bacteroides fragilis
      group isolated from intestinal tracts of calves.
AB  - Species of the Bacteroides fragilis group are considered the most common anaerobe
      in human and animal infections and also harbor plasmids conferring resistance to
      several antibiotics. In this study, resistance to cefoxitin, plasmid profile and
      beta-lactamase production in species of the B. fragilis group isolated from
      intestinal tracts of calves were evaluated. One hundred sixty-one B. fragilis
      group bacteria isolated from calves with and without diarrhea were analyzed.
      Cefoxitin susceptibility was performed using an agar dilution method, beta
      lactamase production by using a nitrocefin method, and plasmid extraction by
      using a commercial kit. Minimal inhibitory concentration values for cefoxitin
      ranged from 32 to > 512 microg/ml, and 47 bacteria (29.2%) were resistant to
      cefoxitin (breakpoint 16 microl). Only seven isolates harbored plasmids varying
      from 6.0 to 5.0 kb, and a 5.5-kb plasmid in B. vulgatus Bd26e and B. fragilis
      Bc5j might be related to cefoxitin resistance. beta-lactamase was detected in 33
      (70.2%) isolates. The cepA gene was observed in total DNA and in the 5.5-kb
      plasmid. The plasmid presence in organisms isolated from cattle may be important
      in ecologic terms, and it needs further study.

PMID- 17019645
TI  - Rapid hybridization probe assay and PCR for detection of Chlamydia trachomatis in
      urinary tract infections: a prospective study.
AB  - Chlamydia trachomatis is a widespread bacterium that causes trachoma and genital
      tract infections in humans. The fact that the growth of this pathogen does not
      normally occur outside living cells poses a challenge in its diagnosis. The
      present study aimed to compare the efficacies of different molecular and cultural
      methods in the detection of C. trachomatis in urine samples collected from
      patients with urinary tract infections. Examined detection methods involved the
      Gen-Probe C. trachomatis (GP-CT) assay, direct antigen detection by enzyme-linked
      immunosorbent assay (ELISA), and polymerase chain reaction (PCR) method. The
      efficacies of these methods were compared to that of the cell culture technique
      depending on sensitivity, specificity, and accuracy. C. trachomatis was detected
      in 25 out of 50 (50%) of examined urine samples using the cell culture method.
      Compared with this standard technique, the GP-CT assay was the most sensitive
      procedure, being able to detect the pathogen in all positive samples, followed by
      PCR and ELISA, which showed 60% and 40% sensitivities, respectively. PCR and
      ELISA displayed the highest level of specificity (100%) compared to the cell
      culture method with the GP-CT assay showing 40% specificity. The rate of accuracy
      was comparable between the GP-CT, PCR, and ELISA methods ranging from 70-80% of
      the accuracy of the cell culture method. The above results suggest that C.
      trachomatis is a frequent pathogen associated with upper and lower urinary tract
      infections. Both the GP-CT assay and PCR method can be recommended as reliable
      detection methods for C. trachomatis, and the GP-CT can be used as a screening
      tool.

PMID- 17019646
TI  - Detection of Helicobacter species in the gastrointestinal tract of wild rodents
      from Brazil.
AB  - Since we have limited knowledge about the occurrence of Helicobacter in wild
      animals, we searched for Helicobacter species in the gastrointestinal tract of 75
      rodents captured in forest remnants of Minas Gerais, Brazil. Fragments from the
      antrum and corpus of the stomach and from the colon were taken for PCR assays for
      Helicobacter detection. Although gastric mucosa was Helicobacter-positive in only
      one animal, the bacterium was detected in the colonic mucosa of 23 rodents
      (30.7%). Helicobacter detection was more frequent in the colon of terraced rice
      rat (56%) and house rat (30%) in contrast to punare and Spix's yellow-toothed
      cavy, in which the presence of the bacterium was not detected. Helicobacter
      rodentium, H. marmotae, H. cinaedi, and other species closely related to the
      murine helicobacters were presumptively identified by DNA sequencing. Wild
      rodents may serve as a reservoir of these Helicobacter species in nature.

PMID- 17019647
TI  - Primary transcripts and expressions of mammal intergenic microRNAs detected by
      mapping ESTs to their flanking sequences.
AB  - MicroRNAs (miRNAs) are a class of approximately 22-nt small RNAs that regulate
      posttranscriptional gene expression. Thousands of expressed sequence tags (ESTs)
      have been identified by using upstream 2500-nt and downstream 4000-nt flanking
      sequences to BLAST in the dbEST database. The cotranscription of the miRNAs and
      their flanking sequences covered by the matched ESTs is verified by RT-PCR. It
      directly reveals that a large portion of mammalian intergenic miRNAs are first
      transcribed as long primary transcripts (pri-miRNAs). Also, the transcripts'
      ranges of tens of pri-miRNAs are predicted by the EST-extension method. We then
      extracted the tissue-specific expression information from the annotations of the
      matched ESTs and established the expression profile of the studied miRNAs for
      tens of tissues. This provided a new way to establish the expression profiles of
      miRNAs. Results show that the human brain, lung, liver, and eye and the mouse
      brain, eye, and mammary gland are tissues in which enriched numbers of miRNAs are
      expressed.

PMID- 17019648
TI  - Intestinal overexpression of ZNF148 suppresses ApcMin/+ neoplasia.
AB  - ZNF148 (ZBP-89, Zfp148) is a multifunctional transcription factor expressed at
      low levels in most tissues. When overexpressed in gastrointestinal cancer cell
      lines, ZNF148 inhibits cellular proliferation and induces apoptosis. We sought to
      determine whether intestinal ZNF148 overexpression would abrogate adenoma
      development in the ApcMin/+ mouse, i.e., whether ZNF148 is a tumor suppressor.
      The 13-kb villin promoter was spliced upstream of the ZNF148 cDNA to generate
      transgenic villin-ZNF148 (ZNF148TgVZ) mice. Intestinal mucosal ZNF148 expression
      was elevated in four of five ZNF148(TgVZ) lineages and correlated with increased
      caspase-3 expression and activation. In addition, DNA fragmentation was increased
      in ZNF148TgVZ mice relative to wild-type littermates. These results suggested
      that increased intestinal ZNF148 expression induces apoptosis. ZNF148TgVZ mice
      were crossed with ApcMin/+ mice to assess the biological significance of
      intestinal ZNF148 overexpression. The presence of the ZNF148TgVZ allele in
      ApcMin/+ mice correlated with reduced gastrointestinal bleeding at 5 weeks, a 50%
      reduction in adenoma burden at 20-22 weeks, and prolonged survival (median
      survival of 33.5 days vs. 21.5 days), relative to nontransgenic littermates.
      These data suggest that enhanced ZNF148 expression activates intestinal apoptosis
      and thereby mitigates disease burden in ApcMin/+ mice. They also suggest that
      ZNF148 is a therapeutic target to inhibit colon cancer development.

PMID- 17019649
TI  - The cld mutation: narrowing the critical chromosomal region and selecting
      candidate genes.
AB  - Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the
      tw73 haplotype on mouse Chromosome 17. While the cld mutation results in lipase
      proteins that are inactive, aggregated, and retained in the endoplasmic reticulum
      (ER), it maps separately from the lipase structural genes. We have narrowed the
      gene critical region by about 50% using the tw18 haplotype for deletion mapping
      and a recombinant chromosome used originally to map cld with respect to the
      phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type
      chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs).
      To identify the affected gene, we have selected candidates based on their known
      role in associated biological processes, cellular components, and molecular
      functions that best fit with the predicted function of the cld gene. A secondary
      approach was based on differences in mRNA levels between mutant (cld/cld) and
      unaffected (+/cld) cells. Using both approaches, we have identified seven
      functional candidates with an ER localization and/or an involvement in protein
      maturation and folding that could explain the lipase deficiency, and six
      expression candidates that exhibit large differences in mRNA levels between
      mutant and unaffected cells. Significantly, two genes were found to be candidates
      with regard to both function and expression, thus emerging as the strongest
      candidates for cld. We discuss the implications of our mapping results and our
      selection of candidates with respect to other genes, deletions, and mutations
      occurring in the cld critical region.

PMID- 17019650
TI  - Identification, genome mapping, and CTCF binding of potential insulators within
      the FXYD5-COX7A1 locus of human chromosome 19q13.12.
AB  - Identification of insulators is one of the most difficult problems in functional
      mapping of genomes. For this reason, up to now only a few insulators have been
      described. In this article we suggest an approach that allows direct isolation of
      insulators by a simple positive-negative selection based on blocking enhancer
      effects by insulators. The approach allows selection of fragments capable of
      blocking enhancers from mixtures of genomic fragments prepared from up to 1-Mb
      genomic regions. Using this approach, a 1-Mb human genome locus was analyzed and
      eight potential insulators were selected. Five of the eight sequences were
      positioned in intergenic regions and two were within introns. The genes of the
      alpha-polypeptide H+/K+ exchanging ATPase (ATP4A) and amyloid beta (A4) precursor
      like protein 1 (APLP1) within the locus studied were found to be flanked by
      insulators on both sides. Both genes are characterized by distinct tissue
      specific expression that differs from the tissue specificity of the surrounding
      genes. The data obtained are consistent with the conception that insulators
      subdivide genomic DNA into loop domains that comprise genes characterized by
      similar expression profiles. Using chromatin immunoprecipitation assay, we
      demonstrated also that at least six of the putative insulators revealed in this
      work could bind the CTCF transcription factor in vivo. We believe that the
      proposed approach could be a useful instrument for functional analysis of
      genomes.

PMID- 17019651
TI  - Molecular definition of an allelic series of mutations disrupting the mouse Lmx1a
      (dreher) gene.
AB  - Mice homozygous for the dreher (dr) mutation are characterized by pigmentation
      and skeletal abnormalities and striking behavioral phenotypes, including ataxia,
      vestibular deficits, and hyperactivity. The ataxia is associated with a
      cerebellar malformation that is remarkably similar to human Dandy-Walker
      malformation. Previously, positional cloning identified mutations in LIM homeobox
      transcription factor 1 alpha gene (Lmx1a) in three dr alleles. Two of these
      alleles, however, are extinct and unavailable for further analysis. In this
      article we report a new spontaneous dr allele and describe the Lmx1a mutations in
      this and six additional dr alleles. Strikingly, deletion null, missense, and
      frameshift mutations in these alleles all cause similar cerebellar malformations,
      suggesting that all dr mutations analyzed to date are null alleles.

PMID- 17019652
TI  - Postnatal lethality and cardiac anomalies in the Ts65Dn Down syndrome mouse
      model.
AB  - The Ts65Dn mouse is a well-studied model for Down syndrome (DS). The presence of
      the translocation chromosome T17 16 (referred to as T65Dn) produces a trisomic
      dosage imbalance for over 100 genes on the distal region of mouse Chromosome 16.
      This dosage imbalance, with more than half of the orthologs of human Chromosome
      21 (Hsa21), causes several phenotypes in the trisomic mice that are reminiscent
      of DS. Careful examination of neonates in a newly established Ts65Dn colony
      indicated high rates of postnatal lethality. Although the transmission rate for
      the T65Dn chromosome has been previously reported as 20%-40%, genotyping of all
      progeny indicates transmission at birth is near the 50% expected with Mendelian
      transmission and survival. Remarkably, in litters with maternal care that allowed
      survival of some pups, postnatal lethality occurred primarily in pups that
      inherited the T65Dn marker chromosome. This selective loss within 48 h of birth
      reduced the transmission of the marker chromosome from 49% at birth to 34% at
      weaning. Gross morphologic examination revealed cardiovascular anomalies, i.e.,
      right aortic arch accompanied by septal defects, in 8.3% of the trisomic newborn
      cadavers examined. This is an intriguing finding because the orthologs of the
      DiGeorge region of HSA22, which are posited to contribute to the aortic arch
      abnormalities seen in trisomy 16 mice, are not triplicated in Ts65Dn mice. These
      new observations suggest that the Ts65Dn mouse models DS not only in its
      previously described phenotypes but also with elevated postnatal lethality and
      congenital heart malformations that may contribute to mortality.

PMID- 17019653
TI  - Cloning, sequencing, and chromosomal localization of pig peripheral
      benzodiazepine receptor: three different forms produced by alternative splicing.
AB  - We report the molecular cloning of the cDNA sequence for pig peripheral
      benzodiazepine receptor (PBR) by using RT-PCR and 5'/3' terminal extension. Three
      different transcripts (long, middle, and short) are identified. The open reading
      frame (ORF) of the longest PBR mRNA encodes a deduced polypeptide of 169 amino
      acids with a calculated molecular weight of 18,609 Da and an estimated pI of
      9.70, which corresponds to the authentic PBR of other mammalian species. The
      middle transcript (PBR-M) contains a 141-codon ORF, which is consistent with that
      of the authentic PBR, but lacks a region of 84 bp so that its encoded polypeptide
      lacks a region of 28 amino acids from 35 to 62 of the authentic PBR polypeptide.
      The short transcript (PBR-S) contains a 104-codon ORF, which overlaps that of the
      authentic PBR, but lacks a region of 211 bp so that its encoded polypeptide lacks
      a region of 65 amino acids of the N-terminal of the authentic PBR. The pig PBR
      gene was mapped to the telomeric end of SSC5p. In addition, PBR mRNA was the more
      abundant detected form in pig tissues and in warm kidney that underwent ischemia
      suggesting functional implications of PBR during the renal repair process.

PMID- 17019654
TI  - Implementation of MR colonography.
AB  - BACKGROUND: MR colonography (MRC) is a promising method of examining the colon,
      but is limited to a few specialist centres. The purpose of this article was to
      describe the implementation of MRC with fecal tagging. MATERIALS AND METHODS:
      Patients referred for conventional colonoscopy (CC) were offered MRC with fecal
      tagging before CC. Two days before MRC patients ingested an oral contrast agent.
      Before and after MRC and CC a number of questions were addressed. MR images were
      rated by a blinded investigator. RESULTS: In 6 months, 30 consecutive patients
      were included. The median time in the MR suite was 44 min, 23 min for the MRC
      examination and 9 min for the evaluation. The median time for CC was 32 min.
      Sixty-six percent of the patients preferred MRC as the future method of
      examination, 10% preferred CC, 21% had no preferences. Of the oral contrast
      agents, barium sulphate with ferumoxsil was significantly better than barium
      sulphate alone. CONCLUSION: The majority of the patients found MRC less
      unpleasant than CC and a majority would prefer MRC over CC as a future colon
      examination. MRC also appears to be less time consuming to the patients and
      medical personnel than CC with post-procedural monitoring.

PMID- 17019655
TI  - Venous thromboembolism: a review of risk and prevention in colorectal surgery
      patients.
AB  - Hospitalization for surgery has a high risk of developing venous thromboembolism,
      a condition that encompasses both deep-vein thrombosis and its potentially fatal
      complication, pulmonary embolism. Colorectal surgery implies a specific high risk
      for postoperative thromboembolic complications relative to other general surgery.
      This may be a result of pelvic dissection, the perioperative positioning of these
      patients, or the presence of additional risk factors common to this patient
      group, such as cancer, advanced age, or inflammatory bowel disease. The potential
      impact of venous thromboembolism and the need for effective thromboprophylaxis
      often are underestimated in these patients. Recommendations for
      thromboprophylaxis in colorectal surgery patients are based on the American
      College of Chest Physicians guidelines for thrombosis prevention in general
      surgery patients, with treatment stratified according to the type of surgery and
      additional venous thromboembolism risk factors present. Prophylaxis with low
      molecular-weight heparin or unfractionated heparin is recommended for colorectal
      surgery patients classified as moderate to high risk. The small number of studies
      focusing specifically on colorectal patients, or on cancer or abdominal surgery
      patients with a colorectal subgroup, has shown that both low-molecular-weight
      heparin and unfractionated heparin can effectively reduce the incidence of venous
      thromboembolism. Low-molecular-weight heparin has the practical advantage of once
      daily administration and shows a lower risk of heparin-induced thrombocytopenia.
      This review will assess the risk of venous thromboembolism in colorectal surgery
      patients and discuss current evidence-based guidelines and recommendations for
      prevention of venous thromboembolism.

PMID- 17019656
TI  - A national study on lymph node retrieval in resectional surgery for colorectal
      cancer.
AB  - PURPOSE: This study was designed to develop a mathematical model for predicting
      the number of lymph nodes harvested in bowel cancer resection specimens based on
      the current clinical practice in the United Kingdom. METHODS: Prospective
      clinical data were collected from 8,409 newly diagnosed bowel cancer patients
      presenting to 79 hospitals in Great Britain and Ireland during a variable 12
      month period from 2000 to 2002. A two-level hierarchical regression model was
      used to identify predictors for lymph node harvest. The model was internally
      validated by comparing observed and model predicted lymph node harvest for
      patient subgroups. RESULTS: Inclusion criteria were satisfied by 5,164 patients.
      The average lymph node harvest was 11.7 nodes with significant between-center
      variability in lymph node harvest (range, 5.5-21.3 nodes). Increasing age,
      American Society of Anesthesiology grade, and preoperative radiotherapy were
      associated with a reduction of lymph node harvest (P < 0.001). Abdominoperineal
      resection of the rectum and transverse colectomy were the lowest yield procedures
      for lymph node harvest. Independent predictors of lymph node harvest were age,
      American Society of Anesthesiology grade, Dukes stage, operative urgency, type of
      resection, and preoperative radiotherapy. When tested, the model was found to
      accurately predict lymph node harvest for group statistics (comparison of
      observed and model predicted lymph node harvest F(1,5154) = 0.63; P = 0.427).
      CONCLUSIONS: The results of the study suggest that the minimum number of lymph
      nodes harvested in colorectal cancer surgery cannot be set at a fixed value. The
      lymph node harvest model provides a simple tool to the frontline clinician for
      comparing standards between multidisciplinary bowel cancer teams.

PMID- 17019657
TI  - Disseminated tumor cells in peripheral blood: a novel marker for therapy response
      in locally advanced rectal cancer patients undergoing preoperative
      chemoradiation.
AB  - PURPOSE: This study was designed to examine whether disseminated tumor cells in
      peripheral blood of locally advanced rectal cancer patients undergoing
      preoperative chemoradiation have the potential to serve as a marker for therapy
      response. Studies suggest that patients with advanced rectal cancer who respond
      to preoperative chemoradiation most likely benefit from this treatment. METHODS:
      From advanced rectal cancer patients undergoing preoperative chemoradiation,
      peripheral blood was obtained at defined times: before, during, and after
      chemoradiation and during surgery. Patients were divided into histopathologic
      responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and
      carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were
      performed to detect disseminated tumor cells. A blood sample was deemed positive
      for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20
      were detected. RESULTS: The overall population (n = 26) showed a positivity rate
      of 32 percent for disseminated tumor cells before initiation of chemoradiation.
      Of the responders (n = 8), 63 percent were positive for disseminated tumor cells
      before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were
      positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a
      significant decrease was seen in tumor cell positivity in the blood of responders
      (P = 0.042). Moreover, the responders represented a trend toward a decrease in
      tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were
      no noticeable alterations within the treatment course in nonresponders.
      CONCLUSIONS: This prospective proof of principle study demonstrates that locally
      advanced rectal cancer with preoperative chemoradiation shows different biologic
      behavior in terms of tumor cell dissemination in peripheral blood when therapy
      responders compared with nonresponders.

PMID- 17019658
TI  - Effect of age and gender on restenosis after carotid endarterectomy.
AB  - Several studies have suggested that the benefits of CEA may be gender-dependent.
      The purpose of this study was to focus on age and gender outcomes after CEA.
      Three hundred seventy-two CEAs were performed in 344 patients (115 females, 229
      males; mean age 72.9 years). Mean follow-up was 25.8 months. Data were collected
      retrospectively by chart review, and follow-up data were obtained by clinical
      examination and duplex ultrasound. Recurrent stenosis was defined as >50% and/or
      occlusion. Three hundred and seventy-two CEAs were performed in 120 female and
      252 male carotid arteries: 97.3% of patients underwent patch angioplasty (bovine
      pericardium 71.5%, Dacron 21.8%, vein 3.8%, and polytetrafluoroethylene 0.3%) and
      2.7% of patients underwent eversion endarterectomy. Perioperative mortality rate
      (30-day) was 0.8% (0% of females vs. 1.2% of males), and stroke rate was 0.5%
      (1.7% of females vs. 0% of males), with no significant gender difference (p =
      0.554 and p = 0.103, respectively). Follow-up ultrasound revealed 21 (7%)
      restenoses (>50%) and/or occlusions, with a significantly higher rate of
      restenosis in females (14% vs. 3.9% in males, p = 0.008) and in patients <70
      years of age at time of surgery (p = 0.003). There was no age difference between
      women and men with restenosis. Although there was no statistical difference in
      occurrence of restenosis between Dacron and bovine patch (p = 0.62), females who
      underwent patch angioplasty with Dacron were more likely to develop restenosis (p
      = 0.052). CEA is a low-risk procedure for significant carotid stenosis; however,
      females are more likely to develop restenosis after carotid surgery, especially
      with Dacron patches. Younger patients appear to be at a higher risk of restenosis
      after surgery.

PMID- 17019660
TI  - Catheter lock solutions: it's time for a change.
AB  - In recent years, the number of patients on hemodialysis (HD) with central
      vascular catheters (CVCs) has grown. However, CVC use is often associated with an
      important risk for catheter related bloodstream infections (CR-BI) and inadequate
      dialysis due to flow problems. In this study, we reviewed alternative solutions
      to heparin for locking HD CVCs. Several experiences have demonstrated that
      trisodium citrate (TSC) (30-47%), citrate (4%) and taurolidine (1.35%) solutions
      are effective and safe for the prevention of CRBI, while heparin stimulates
      biofilm formation. High citrate (47%) concentrations can also provide significant
      advantages in reducing catheter clotting, but controlled studies with larger
      populations are necessary to confirm and to extend the use of such solutions in
      clinical practice. Side effects with high sodium citrate concentrations have been
      reported only immediately after locking, the symptoms are probably caused by a
      temporary drop in ionized calcium and magnesium, but it is evident that these
      solutions should only be used by skilled and authorized personnel, with a
      rigorous protocol.

PMID- 17019661
TI  - The endless history of vascular access: a surgeon's perspective.
AB  - Gaining access to blood circulation has been a major breakthrough of modern
      medical care and, despite the evolution of dialysis technology, vascular access
      (VA) remains the main impediment in providing quantity as well as quality of life
      to the end-stage renal disease (ESRD) patient. The external Scribner shunt and
      the internal Brescia/Cimino arteriovenous fistula (AVF) opened the way for
      further advancements such as graft angioaccess and other sophisticated devices.
      Forty years later, the radio-cephalic fistula remains the VA with the longest
      patency and the lowest complications. Although various technical solutions can be
      adopted for constructing access to the patient's vessels, the nephrologist must
      bear in mind that every VA in the upper limb, lower limb or body wall needs a run
      in and a run-off: currently, thrombosis of the central vessels due to the
      excessive widespread use of central venous catheters (CVCs) emerge as a
      substantial cause of hemodialysis (HD) morbidity and mortality. Moreover, as
      there is a risk of central vein stenosis, even 2 weeks after catheter placement,
      and an impaired venous outflow precludes the creation of any VA and sometimes the
      placement of a kidney transplant in the iliac fossa for many years, we agree with
      McGill et al, who in 2005 said that ''expansion of catheter access may contribute
      to the reduced survival of hemodialysis patients in the United States''.

PMID- 17019662
TI  - Delivery of intravenous treprostinil at low infusion rates using a miniaturized
      infusion pump in patients with pulmonary arterial hypertension.
AB  - PURPOSE: Treprostinil is approved for the treatment of pulmonary arterial
      hypertension (PAH) via continuous intravenous (IV) infusion. Treprostinil's anti
      platelet aggregation characteristics and stability at room temperature may allow
      for low infusion rates (0.1-0.2 mL/hr) using a miniaturized infusion pump.
      METHODS: A 12-week, multi-center, open-label study in 12 adult PAH patients,
      evaluated the feasibility and safety of low-flow IV treprostinil administration
      via the 407C miniaturized pump. Patients receiving IV treprostinil at a stable
      dose were transitioned from their current CADD-Legacy pump to the 407C and were
      assessed for adverse events including catheter occlusions, pump alarms, and
      efficacy (six minute walk distance (6MWD), Borg Dyspnea Score (BDS), NYHA
      functional class, and PAH signs/symptoms). All patients were also maintained on
      therapeutic doses of warfarin, heparin or low molecular weight heparin throughout
      the study. RESULTS: Baseline mean (+/-SD) 6MWD was 477 +/- 76 m (n = 9) with mean
      BDS of 2.1 +/- 1.2 (n = 9). Week 12 mean 6MWD and BDS were 500 +/- 92 m and 2.3
      +/- 1.7, respectively (n = 9). Four patients discontinued the study prematurely
      (3 AEs and 1 consent withdrawn). Adverse events included headache, flushing, and
      nausea. Pump complications occurred in 5 of 12 patients, and although no catheter
      occlusions occurred in any patient during the 12-week study, further study is
      needed regarding pump complications. CONCLUSION: This study demonstrates that
      treprostinil can be administered intravenously at infusion rates as low as 0.1
      mL/hr for 12 weeks without catheter occlusions. Further studies are warranted
      because the potential for adverse events is of some concern.

PMID- 17019663
TI  - Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed
      catheters (TCC) thrombosis.
AB  - BACKGROUND: Chronic oral anticoagulation is currently used to avoid thrombosis
      and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD).
      The aim of the study was to assess the efficacy of early warfarin administration,
      after TCC placement, in comparison to its administration after the first
      thrombosis or malfunction event of the TCC. PATIENTS AND METHODS: One hundred and
      forty-four chronic dialysis patients, who underwent TCC placement between June
      2001 and June 2005, were randomized into two groups: 81 patients, group A,
      started oral anticoagulation 12 hr after the TCC placement (target international
      normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63
      patients, group B, started warfarin after the first thrombosis/malfunction
      episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The
      efficacy of oral anticoagulation therapy in preventing TCC thrombotic
      complications was evaluated in a 12-month follow-up period, after TCC placement,
      in terms of: a) the number of patients with thrombotic-malfunction events; b) the
      number of thrombotic-malfunction events with urokinase infusion
      (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d)
      negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e)
      positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and
      f) bleeding complications. RESULTS: Ten patients (12%) in group A showed TCC
      thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A,
      0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p <
      0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p <
      0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05).
      VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No
      patient showed any bleeding events. CONCLUSIONS: Early warfarin therapy allows a
      significant reduction in TCC thrombotic complications and an improvement in both
      arterial and venous fluxes in comparison with the same therapy administered after
      the first TCC thrombotic/malfunction event. This therapy did not induce any
      bleeding complications in the patients included in the study.

PMID- 17019664
TI  - Impact of pre-operative venography on the planning and outcome of vascular access
      for hemodialysis patients.
AB  - OBJECTIVE: Pre-operative venous mapping has increased dramatically in most
      dialysis units since the Dialysis Outcome Quality Initiative (DOQI) guidelines
      recommended a native arteriovenous venous fistula (AVF) rather than a graft for
      hemodialysis (HD) access procedures. However, there are conflicting consequences
      as a result of this policy. Some studies have showed that routine mapping has
      resulted in a marked increase in maturation rate while others have observed the
      reverse. This study aimed to evaluate the impact of pre-operative venography on
      the planning and outcome of AVF for our HD patients. PATIENTS AND METHODS: A
      prospective study was performed on all patients with end-stage renal disease
      (ESRD) who had HD access procedures and pre-operative venography between October
      2003 and November 2005. Upper limb venography was done for all patients except
      those that required primary access and had visible veins. All patients had HD
      immediately after the venography. Access procedure selection was based on the
      result of the venography. The complications of venography, the surgical procedure
      and the outcome were recorded. RESULTS: One hundred and twenty-nine patients with
      ESRD who had pre-operative venography were included in this study. They were
      mostly middle age (mean age +/- SD = 41 +/- 15.5 yrs) with a high rate of
      diabetes mellitus (53%). No single complication was reported. A graft was placed
      in six patients (5%) only. Unsuccessful surgical exploration was 0%. Early
      failure was in 10 patients (8%). CONCLUSION: Pre-operative venography resulted in
      an increase in the number of AVFs. It can improve the results of HD access
      procedures by selecting the most suitable veins.

PMID- 17019665
TI  - Median nerve bisection: a morbid complication of a peripherally inserted central
      catheter.
AB  - Considering the reported safety, efficiency, and low cost of peripherally
      inserted central catheters (PICCs), they are increasingly preferred to central
      venous catheters for short-term delivery of medical therapies. Here, we report a
      case of severe median nerve bisection during PICC placement via a brachial vein.
      While such nerve damage is uncommon, the case indicates that when the brachial
      vein is selected as an access site over the basilic and cephalic veins, caution
      should be exercised during PICC placement since the brachial vein traverses in
      close proximity to the median nerve.

PMID- 17019666
TI  - Dislocation of central venous catheters in paediatric patients.
AB  - Children have limited venous access possibilities; therefore, when long-term
      therapy is necessary, it is better to place a catheter in a central vein. The
      Port catheter, totally implanted, is less exposed to the risk of infection and
      permits a normal life. However, there is the possibility of the displacement or
      fragmentation of the catheter that can be diagnosed initially only by clinical
      symptoms and later by a chest X-ray. We report a case of disconnection between
      the Port catheter and the reservoir resulting in catheter migration to the left
      pulmonary artery.

PMID- 17019667
TI  - Carotid artery repair after erroneous insertion of a hemodialysis catheter: case
      report.
AB  - The internal jugular vein is increasingly being used as a route for dual-lumen
      hemodialysis catheter placement. The use of jugular catheters as vascular access
      for hemodialysis can be associated with serious complications. The most frequent
      problems are the arterial puncture and haematoma. We present a rare complication
      of catheterization of the right common carotid artery during dual-lumen catheter
      placement into the right internal jugular vein. The complication was diagnosed
      the next day and the catheter was removed operatively. A review of the literature
      on complicated carotid artery catheterization is also presented.

PMID- 17019668
TI  - Pulmonary atheroembolism via an AV shunt.
AB  - Although cholesterol crystal embolism can present with diffuse visceral
      involvement, lung lesions do not occur unless there is left to right circulatory
      shunting. Pulmonary atheroembolism was confirmed by histology in an elderly male
      with recent end-stage renal failure (ESRF) due to atheroembolic renal disease,
      who presented with massive hemoptysis and intractable respiratory failure. At
      autopsy, atheromatous degeneration of the aorta was observed and acute
      cholesterol emboli found in the kidneys, spleen, liver, stomach and lung.
      Cholesterol clefts were seen in pulmonary arterioles, and ischemic alveolar
      damage was present. The pulmonary arteries had no atheromatous changes.
      Intrapulmonary, intracardiac, and aortocaval shunting were not present. Pulmonary
      atheroembolism arising from a dialysis fistula has not been previously reported.

PMID- 17019669
TI  - Guanidination chemistry for qualitative and quantitative proteomics.
AB  - The application of guanidination chemistry, the conversion of lysine into
      homoarginine residues, is used to illustrate several important general
      considerations relating to the use of differential isotope labelling for relative
      quantification in proteomics. The derivatisation procedure has been optimised for
      automation using a liquid handling station designed for proteomics. Automated
      application of the procedure to the analysis of in-gel tryptic digests of
      multiple spots from the two-dimensional gel electrophoretic (2DE) analysis of
      proteins from the FDCP-mix cell line shows near-universal improvement in protein
      identification as a result of derivatisation. This chemistry has been extended
      for relative quantification, applicable to matrix-assisted laser
      desorption/ionisation mass spectrometry (MALDI-MS) and also tandem mass
      spectrometry (MS/MS). It provides a robust method for the quantitative comparison
      of two samples that have been separated by 2DE. A peptide pair may display poor
      detection during MS analysis, causing their reliable relative quantification to
      be difficult. In such circumstances, the additional selectivity of detection
      provided by MS/MS can substantiate identification and allow relative
      quantification of these species via product ion signal ratios.

PMID- 17019670
TI  - Unambiguous identification of thiouracil residue in urine collected in non
      treated bovine by tandem and high-resolution mass spectrometry.
AB  - Thyrostats are banned compounds in Europe since 1981 (directive 81/602/EC)
      because of their carcinogenic and teratogenic properties. However, the occurrence
      of thiouracil (TU) in bovine urines from national monitoring plans with
      quantifications in the range 1-10 microg . L(-1) occasionally raises the question
      of its origin which might either be the consequence of an illegal administration
      or the result of 'endogenous' production. In order to definitively and
      unambiguously identify the so-called thiouracil signal in non-treated bovine
      urines, independent mass spectrometry (MS) approaches have been used. Different
      reagents (3-IBBr, 3-BrBBr and PFBBr) were used to derivatise and to extract TU
      from urine samples and characterisation of the residues was performed by means of
      different MS approaches [LC/(ESI-)MS/MS, GC/(EI+)MS/MS and HRMS (EI and NCI)].
      These combined strategies allowed for an independent and confident identification
      of TU in bovine urine samples collected from animals never treated with any
      thyrostatic drugs. This result is of prime importance for laboratories and risk
      managers involved in the field of forbidden growth promoters control: detection
      of TU residue in bovine urine will have to be carefully considered as a non
      systematic proof of illegal administration.

PMID- 17019671
TI  - Coaxial multi-electrode cell ('O-trap') for high-sensitivity detection at a
      multiple frequency in Fourier transform ion cyclotron resonance mass
      spectrometry: main design and modeling results.
AB  - Separation of the functions of ion excitation and detection between different
      cell compartments allows for implementation of excitation and detection
      techniques unattainable in a single compartment of the conventional ion cyclotron
      resonance (ICR) cell. In particular, multi-electrode detection at a multiple of
      the main cyclotron frequency can be utilized without the loss of sensitivity and
      other negative effects. The new O-trap designed exclusively for ion detection
      adds an additional, internal coaxial cylinder around which ions with excited
      cyclotron orbits rotate. Comparison of simulated performance characteristics of
      the new O-trap with those of the same-size conventional cylindrical cell shows
      that the O-trap can provide higher sensitivity and ion capacity. Multiplexing of
      the O-traps can further increase the analysis speed. Future efforts will be aimed
      at building and testing experimentally the coaxial O-trap, including optimization
      of the method of ion transfer between the compartments of the cell.

PMID- 17019672
TI  - Examining the links between spiritual struggles and symptoms of psychopathology
      in a national sample.
AB  - The present study investigated the relationship between spiritual struggles and
      various types of psychopathology symptoms in individuals who had and had not
      suffered from a recent illness. Participants completed self-report measures of
      religious variables and symptoms of psychopathology. Spiritual struggles were
      assessed by a measure of negative religious coping. As predicted, negative
      religious coping was significantly linked to various forms of psychopathology,
      including anxiety, phobic anxiety, depression, paranoid ideation, obsessive
      compulsiveness, and somatization, after controlling for demographic and religious
      variables. In addition, the relationship between negative religious coping and
      anxiety and phobic anxiety was stronger for individuals who had experienced a
      recent illness. These results have implications for assessments and interventions
      targeting spiritual struggles, especially in medical settings.

PMID- 17019673
TI  - The Toronto Mindfulness Scale: development and validation.
AB  - In this study, the authors both developed and validated a self-report mindfulness
      measure, the Toronto Mindfulness Scale (TMS). In Study 1, participants were
      individuals with and without meditation experience. Results showed good internal
      consistency and two factors, Curiosity and Decentering. Most of the expected
      relationships with other constructs were as expected. The TMS scores increased
      with increasing mindfulness meditation experience. In Study 2, criterion and
      incremental validity of the TMS were investigated on a group of individuals
      participating in 8-week mindfulness-based stress reduction programs. Results
      showed that TMS scores increased following treatment, and Decentering scores
      predicted improvements in clinical outcome. Thus, the TMS is a promising measure
      of the mindfulness state with good psychometric properties and predictive of
      treatment outcome.

PMID- 17019674
TI  - Measuring hedonic capacity in depression: a psychometric analysis of three
      anhedonia scales.
AB  - The present study evaluated and compared the psychometric properties of three
      self-report scales: the Snaith-Hamilton Pleasure Scale (SHAPS; R. P. Snaith, M.
      Hamilton, S. Morley, & A. Humayan, 1995), Fawcett-Clark Pleasure Capacity Scale
      (FCPS; J. Fawcett, D. C. Clark, W. A. Scheftner, & R. D. Gibbons, 1983), and the
      Revised Chapman Physical Anhedonia Scale (CPAS; L. J. Chapman, J. P. Chapman, &
      M. L. Raulin, 1976). These scales, designed to assess hedonic responsiveness,
      were administered to 157 college students. Confirmatory factor analysis revealed
      a Hedonic Capacity factor that was largely defined by the SHAPS but also had a
      substantial loading from the FCPS. Hedonic Capacity was minimally correlated with
      constructs of Depression and Anxiety, which were assessed by the Beck Depression
      Inventory-II and the Beck Anxiety Inventory. The CPAS (anhedonia) was not
      significantly related to Hedonic Capacity or Anxiety, but it did have a small
      positive loading on Depression. These findings suggest that further research is
      needed to clarify the meaning of and relationships among scales that are putative
      indicators of hedonic capacity and anhedonia.

PMID- 17019675
TI  - Data mining for signals in spontaneous reporting databases: proceed with caution.
AB  - PURPOSE: To provide commentary and points of caution to consider before
      incorporating data mining as a routine component of any Pharmacovigilance
      program, and to stimulate further research aimed at better defining the
      predictive value of these new tools as well as their incremental value as an
      adjunct to traditional methods of post-marketing surveillance. METHODS/RESULTS:
      Commentary includes review of current data mining methodologies employed and
      their limitations, caveats to consider in the use of spontaneous reporting
      databases and caution against over-confidence in the results of data mining.
      CONCLUSIONS: Future research should focus on more clearly delineating the
      limitations of the various quantitative approaches as well as the incremental
      value that they bring to traditional methods of pharmacovigilance.

PMID- 17019676
TI  - Potential opportunity in the development of new therapeutic agents based on
      endogenous and exogenous inhibitors of the proprotein convertases.
AB  - The proprotein convertases (PCs) are responsible for the endoproteolytic
      processing of various protein precursors (e.g., growth factors, receptors,
      adhesion molecules, and matrix metalloproteinases) implicated in several diseases
      such as obesity, diabetes, atherosclerosis, cancer, and Alzheimer disease. The
      potential clinical and pharmacological role of the PCs has fostered the
      development of various PC-inhibitors. In this review we summarized the recent
      findings on PCs inhibitors, their mode of actions and potential use in the
      therapy of various diseases.

PMID- 17019677
TI  - Antennal structure of male and female Aphidius rhopalosiphi DeStefani-Peres
      (Hymenoptera:Braconidae): description and morphological alterations after cold
      storage or heat exposure.
AB  - Several species of the genus Aphidius are used in biological control programs
      against aphid pests throughout the world and their behavior and physiology are
      well studied. But despite knowing the importance of sensory organs in their
      behavior, their antennal structure has never been described. We describe here the
      types and distribution of antennal sensilla in Aphidius rhopalosiphi, a larval
      parasitoid of several aphid species and observe how this antennal structure is
      modified after cold storage or heat exposure. Six types of sensilla were found on
      both male and female antennae. Male and female antennae differed in the total
      number of antennomeres (16 in males, 14 in females) and in the number and
      distribution of three of the six types of sensilla. After cold storage or heat
      exposure, we observed the appearance of a small number of abnormal sensilla.

PMID- 17019678
TI  - Molecular mechanism of emodin action: transition from laxative ingredient to an
      antitumor agent.
AB  - Anthraquinones represent a large family of compounds having diverse biological
      properties. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a naturally
      occurring anthraquinone present in the roots and barks of numerous plants, molds,
      and lichens, and an active ingredient of various Chinese herbs. Earlier studies
      have documented mutagenic/genotoxic effects of emodin, mainly in bacterial
      system. Emodin, first assigned to be a specific inhibitor of the protein tyrosine
      kinase p65lck, has now a number of cellular targets interacting with it. Its
      inhibitory effect on mammalian cell cycle modulation in specific oncogene
      overexpressed cells formed the basis of using this compound as an anticancer
      agent. Identification of apoptosis as a mechanism of elimination of cells treated
      with cytotoxic agents initiated new studies deciphering the mechanism of
      apoptosis induced by emodin. At present, its role in combination chemotherapy
      with standard drugs to reduce toxicity and to enhance efficacy is pursued
      vigorously. Its additional inhibitory effects on angiogenic and metastasis
      regulatory processes make emodin a sensible candidate as a specific blocker of
      tumor-associated events. Additionally, because of its quinone structure, emodin
      may interfere with electron transport process and in altering cellular redox
      status, which may account for its cytotoxic properties in different systems.
      However, there is no documentation available which reviews the biological
      activities of emodin, in particular, its growth inhibitory effects. This review
      is an attempt to analyze the biological properties of emodin, a molecule offering
      a broad therapeutic window, which in future may become a member of anticancer
      armamentarium.

PMID- 17019679
TI  - Prenatal stress and early adoption effects on benzodiazepine receptors and
      anxiogenic behavior in the adult rat brain.
AB  - Chronic maternal stress during pregnancy has been associated with behavioral
      alterations that persist into adulthood. Moreover, adoption procedures performed
      immediately after birth can reverse these alterations. In this study, we examined
      the effects of prenatal restraint stress and adoption at birth (cross-fostering)
      on the behavioral response to an anxiety-provoking situation and on the adult
      male offspring expression of benzodiazepine (BDZ) receptors in selected brain
      areas. Adult offspring of rats stressed during the last week of pregnancy
      exhibited higher levels of anxiety than control rats. The anxiogenic behavior
      found at the elevated plus maze (EPM) has been related to the reduced levels of
      BDZ receptor levels in specific brain areas. Adult offspring of rats stressed
      during pregnancy exhibited a decrease in the number of BDZ receptors binding
      sites in the central amygdaloid nucleus (Ce), CA1, CA3, and the dentate gyrus
      regions of the hippocampus when compared to controls. Regarding the adoption
      procedure, control pups raised by a foster gestationally stressed mother showed
      similar levels of anxiety as stressed groups. Stressed offspring raised by a
      foster control mother showed reduced anxiety levels compared to that of the
      control groups. Adoption per se showed no difference in time spent, neither in
      the open arms of the plus maze nor in BDZ receptor levels, when compared to the
      corresponding control and stressed groups. Stressed offspring raised by a foster
      control mother reverted BDZ receptor levels to control values. However, control
      pups raised by a gestationally stressed foster mother showed similar values
      compared to the control offspring in hippocampus, in spite of showing an
      anxiogenic behavior in the EPM. We found a significant increase of Ce BDZ
      receptor levels in control offspring raised by a foster stressed mother that
      could be explained as a compensatory effect to a GABA receptor desensitization.
      In summary, the behavioral outcome of the adult offspring is vulnerable both to
      the stress experience during the late prenatal period as well as to possible
      variations in care during lactation by mothers subjected to chronic stress during
      gestation. There seems to be a direct correlation between anxiety state and BDZ
      receptor levels in the adult offspring raised by their biological mothers.
      However, the mechanism of BDZ regulation leading to an anxious behavior might be
      different if the insult is received only postnatally as opposed to both pre and
      postnatally.

PMID- 17019680
TI  - Cellular uptake mechanisms and potential therapeutic utility of peptidic cell
      delivery vectors: progress 2001-2006.
AB  - Cell delivery vectors (CDVs) are short amphipathic and cationic peptides and
      peptide derivatives, usually containing multiple lysine and arginine residues.
      They possess inherent membrane activity and can be conjugated or complexed with
      large impermeable macromolecules and even microscopic particles to facilitate
      cell entry. Various mechanisms have been proposed but it is now becoming clear
      that the main port of entry into cells of such CDV constructs involves adsorptive
      mediated endocytosis rather than direct penetration of the plasma membrane. It is
      still unclear, however, how and to what extent CDV constructs are capable of
      exiting endosomal compartments and reaching their intended cellular site of
      action, usually the cytosol or the nucleus. Furthermore, although many CDVs can
      mediate cellular uptake of their cargo and appear comparatively non-toxic to
      cells in tissue culture, the utility of CDVs for in vivo applications remains
      poorly understood. Whatever the mechanisms of cell entry and disposition, the
      overriding question as far as potential pharmacological application of CDV
      conjugates is concerned is whether or not a therapeutic margin can be achieved by
      their administration. Such a margin will only result if the intracellular
      concentration in the target tissues necessary to elicit the biological effect of
      the CDV cargo can be achieved at systemic CDV exposure levels that are non-toxic
      to both target and bystander cells. It is proposed that the focus of CDV research
      now be shifted from mechanistic in vitro studies with labeled but otherwise
      unconjugated CDVs to in vivo pharmacological and toxicological studies using CDV
      derivatized and other cationized forms of inherently non-permeable macromolecules
      of true therapeutic interest.

PMID- 17019681
TI  - Development of a biodegradable alginate carrier system for antibiotics and bone
      cells.
AB  - This study presents a novel biodegradable alginate delivery system for
      antibiotics and bone cells to treat infected bone defects. About 2 x 10(7) New
      Zealand rabbit mesenchymal stem cells (MSCs) and 5 mL vancomycin solution (50
      mg/mL) were added to 5 mL of 2.5% (w/v) sodium alginate solution to form
      biodegradable antibiotic and MSCs alginate beads 3 mm in diameter. The alginate
      beads were then cultured in an osteogenic medium for 14 days. The profiles of
      antibiotics released from the alginate beads were evaluated using the method of
      high performance liquid chromatography (HPLC). The expression of osteogenic
      genes, including Cbfa1 and osteopontin, in the alginate beads was determined by
      reverse transcription-polymerase chain reaction (RT-PCR) analysis. The alkaline
      phosphatase activity, calcium level, and mineral deposition of the cultured cells
      within the alginate beads were assessed. Analytical results demonstrated that the
      concentrations of vancomycin eluted from the alginate beads were, for 14 days,
      well above the minimal inhibitory concentration of Staphylococcus aureus.
      Osteopontin and mRNA of Cbfa1 were detected and increased alkaline phosphatase
      activity and calcium levels were noted, as was a substantial mineral deposition
      in cultured MSCs. The PKH 26-labeled MSCs and vancomycin alginate beads were
      implanted in rabbit bony cavities for in vivo analysis. Implanted PKH 26-labeled
      MSCs were identified in the newly formed bony trabeculae in all specimens at 2
      and 4 months after implantation and there was abundant mineral deposition. The
      results of in vitro study demonstrated sustained elution of vancomycin from the
      alginate carrier for 14 days and good osteogenic differentiation of cultured MSCs
      in the alginate carrier matrix. The results of in vivo study demonstrated the
      implanted MSCs participating in new bone formation. Based on experimental
      evidence, development of a biodegradable alginate carrier system for antibiotics
      and bone cells is possible, providing a potential treatment procedure for
      infected bone defects.

PMID- 17019682
TI  - Quantitative and topographical evaluation of ankle articular cartilage using high
      resolution MRI.
AB  - The objectives of this study were to quantitatively evaluate the articular
      cartilage layers of the ankle and describe the cartilage topographical
      distribution across the joint surfaces using high resolution MRI and image
      segmentation. An anisotropic diffusion noise reduction algorithm and a
      directional gradient vector flow (dGVF) snake segmentation algorithm were applied
      to cartilage sensitive MR images. Eight cadaveric ankles were studied. Six
      repeated data sets were acquired in five of the ankles. Quantitative parameters
      were calculated for each cartilage layer; coefficients of variation (CV) were
      calculated from the six repeated data sets; and 3D thickness distribution maps
      were generated. The noise reduction algorithm produced marked image enhancement.
      Mean cartilage thickness ranged from 0.91 +/- 0.08 mm in the fibula to 1.34 +/-
      0.14 mm in the talus. Mean cartilage volume was 3.32 +/- 0.55 ml, 1.72 +/- 0.25
      ml, and 0.35 +/- 0.06 ml for the talus, tibia, and fibula, respectively. Mean CV
      ranged 2.82%-5.04% for quantitative parameters in the talus and tibia. The
      reported noise reduction and segmentation technique allow precise extraction of
      ankle cartilage and 3D reconstructions show that the thickest cartilage occurs
      over the talar shoulders, where osteochondritits dissecans (OCD) lesions commonly
      occur.

PMID- 17019683
TI  - Femoral rollback of cruciate-retaining and posterior-stabilized total knee
      replacements: in vivo fluoroscopic analysis during activities of daily living.
AB  - Restoration of the physiological flexor/extensor mechanism at the knee in terms
      of appropriate muscular lever arms, proper required quadriceps force, and
      suitable patellofemoral compressive force, is fundamental for the success of
      total knee replacement. Therefore, measurements of anteroposterior translation of
      the femoral component over the tibial base-plate against joint flexion during
      daily living activities are essential for the assessment of the in vivo
      performance of current prosthesis designs. Patients treated with posterior
      stabilized and cruciate retaining prostheses with excellent clinical scores were
      evaluated during stair climbing, sitting and rising from a chair, and step up and
      down, using a three-dimensional pose reconstruction technique based on
      videofluoroscopy. The posterior stabilized patients experienced a fairly
      consistent and physiological rollback specific of each motor task, demonstrating
      proper function of the spine-cam mechanism. Rollback was somehow inconsistent
      among subjects in the cruciate retaining group, accompanied with a smaller range
      of knee flexion. In this group, more posterior locations of the condyles
      correlated significantly with higher clinical and functional scores. Articular
      surface conformity restores physiological rollback in the presence of a spine-cam
      mechanism, but not coherently in the presence of the posterior cruciate ligament.

PMID- 17019684
TI  - A hinge of the endogeneous ATP synthase inhibitor protein: the link between
      inhibitory and anchoring domains.
AB  - The ATP synthase of bovine heart mitochondria possesses a regulatory subunit
      called the endogenous inhibitory protein (IF(1)). This subunit regulates the
      catalytic activity of the F(1) sector in the mitochondrial inner membrane. When
      DeltamuH(+) falls, IF(1) binds to the enzyme and inhibits ATP hydrolysis. On the
      other hand, the establishment of a DeltamuH(+) induces the release of the
      inhibitory action of IF(1), allowing ATP synthesis to proceed. IF(1) is also
      involved in the dimerization of soluble F(1). Dynamic domain analysis and normal
      mode analysis of the reported crystallographic structure of IF(1) revealed that
      it has an effective hinge formed by residues 46-52. Molecular dynamics data of a
      27 residue fragment confirmed the existence of the hinge. The hinge may act as a
      regulatory region that links the inhibitory and anchoring domains of IF(1). The
      residues assigned to the hinge are conserved between mammals, but not in other
      species, such as yeasts. Likewise, unlike the heart inhibitor, the yeast protein
      does not have the residues that allow it to form stable dimers through coiled
      coil interactions. Collectively, the data suggest that the hinge and the
      dimerization domain of the inhibitor protein from bovine heart are related to its
      ability to form stable dimers and to interact with other subunits of the ATP
      synthase.

PMID- 17019685
TI  - Solution structure of TA0895, a MoaD homologue from Thermoplasma acidophilum.

PMID- 17019686
TI  - Tandem high-dose chemotherapy and autologous stem cell transplantation in
      refractory/relapsed Hodgkin's lymphoma: a monocenter prospective study.
AB  - We designed a prospective study to evaluate the feasibility and efficacy of
      tandem high-dose chemotherapy (HDCT) in the treatment of refractory or relapsed
      Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage
      chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive
      patients received a first HDCT course with melphalan 200 mg/m(2) (MEL200) and a
      second BEAM course. The median time interval between the two HDCT courses was 66
      days. The median number of reinfused CD34(+) cells was 4.7 x 10(6)/kg after
      MEL200 and 5.8 x 10(6)/kg after BEAM. The hematological reconstitution after both
      HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac,
      and neurological toxicity was observed. Severe (grade III and IV) oral mucositis
      was the most prominent complication affecting 60 and 50% of patients after MEL200
      and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of
      patients after MEL200 and BEAM, respectively. One patient died from septic shock
      during the aplasia period following BEAM. In an intention-to-treat analysis, the
      overall response rate increased after each stage of protocol, ranging from 47% to
      65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible
      and effective in patients with relapsed or refractory HL.

PMID- 17019687
TI  - Aberrant expression of T-cell-associated markers CD4 and CD7 on B-cell chronic
      lymphocytic leukemia.
AB  - By multiparameter flow cytometry, the T-cell-associated markers CD4 and CD7 were
      aberrantly coexpressed on a case of B-cell chronic lymphocytic leukemia (CLL).
      The CLL had an immunophenotype: CD19+, CD20+, CD79b+, CD5+, CD23+, FMC7+, kappa+,
      CD4+, and CD7+. Molecular analysis confirmed clonal rearrangement of the
      immunoglobin heavy chain genes and a germline configuration of the T-cell
      receptor genes. Fluorescence in situ hybridization showed trisomy 12 anomaly.
      There was no evidence of deletion 17p (p53), 11q23 (ATM), or 13q14 or
      translocation t(11:14). The patent was clinically stable without treatment.
      Although the pathogenesis of such aberrant immunophenotype remains to be
      determined, the current case illustrates the phenotypic heterogeneity of CLL, and
      emphasizes the importance of a comprehensive diagnostic approach including
      clinical, morphologic, immunophenotypic, and molecular cytogenetic studies.

PMID- 17019688
TI  - Fas expression in DLBCL.

PMID- 17019690
TI  - Rituximab monotherapy as interim therapy in precursor B-ALL adults during periods
      of hepatic toxicity: report of two cases.
AB  - Precursor B-ALL blasts may be positive for CD20 in up to 50% of cases. There are
      few reports on the use of the anti CD20 monoclonal antibody, rituximab, in
      children with B-ALL. We report on two adult patients with precursor B-ALL who
      developed significant hepatic toxicity during induction chemotherapy. Single
      agent rituximab was given until recovery of liver enzymes was established. Both
      patients were able to continue further chemotherapy, underwent an Allo BMT and
      are now 10-12 months after diagnosis in a continuous CR.

PMID- 17019689
TI  - Iron status of inner-city African-American infants.
AB  - The iron status of African-American infants continues to be subject to debate. We
      characterized the iron status of 198 9-month-old inner-city infants (94% fed iron
      fortified formula) using a comprehensive panel of measures and assessing lead and
      inflammation markers. The proportion with iron deficiency was calculated based on
      three approaches (> or = 2 abnormal iron measures with or without anemia for MCV
      model--NHANES II, ferritin model--NHANES III, or Sweden/Honduras study) and a
      promising new measure-body iron, calculated from ferritin and transferrin
      receptor (TfR). There were no sex differences for any iron measure. Hb < 110 g/l
      was observed in 25%; Hb < or = 105 g/l in 10.1%. Free erythrocyte protoporphyrin
      (FEP) values were elevated without elevated lead concentrations or an
      inflammatory response: mean FEP = 86.6 microg/dl red blood cells [75.5
      micromol/mol heme]; 52.3% were > 80 microg/dl (1.42 micromol/l), almost half of
      which were accompanied by a second abnormal iron measure. The estimated
      prevalence of iron deficiency was 14.4, 5.3, and 2.5% for the MCV model, ferritin
      model, and Sweden/Honduras cutoffs, respectively, and 4.1% for body iron < 0
      mg/kg. Regulation of iron storage is immature at < 1 year of age, making
      estimates of iron deficiency that depend on ferritin, including body iron,
      suspect in this age period. Thus, the "true" prevalence of iron deficiency could
      not be established with confidence due to major differences in the results,
      depending on the guidelines used. Functional indicators of poor iron status in
      young infants are urgently needed.

PMID- 17019691
TI  - De novo CD5+ diffuse large B cell lymphoma with basophilia in the peripheral
      blood: successful treatment with autologous peripheral blood stem cell
      transplantation.
AB  - Basophils play an important role in allergic inflammation and are pathologically
      related to hematological disturbances, such as iron deficiency anemia and
      myeloproliferative disorders; however, they are only rarely encountered in
      lymphoid malignancies. Here, we report the case of a 33-year-old man with a bulky
      mass of the small intestine, multiple paraaortic lymphoadenopathy, pleural
      effusion, and ascites, who was diagnosed as a case of de novo CD5+ diffuse large
      B cell lymphoma (DLBCL). This patient showed a marked elevation of the basophil
      count in the peripheral blood, which appeared to run in parallel with the tumor
      burden. High dose chemotherapy followed by autologous peripheral blood cell
      transplantation yielded complete remission, and the patient has remained disease
      free for 5 years. To the best of our knowledge, this is the first report of a
      case of de novo CD5+ DLBCL showing marked elevation of the PB basophil count.

PMID- 17019692
TI  - Paraplegia as the presenting manifestation of extramedullary megakaryoblastic
      transformation of previously undiagnosed chronic myelogenous leukemia.
AB  - Extramedullary tumors, also known as granulocytic sarcomas (GS), occur most
      frequently in acute myelogenous leukemia (AML). They may signal the onset of the
      accelerated phase of chronic myelogenous leukemia (CML) or the blastic
      transformation of a myeloproliferative disorder. Occasionally, a GS may be the
      presenting sign of undiagnosed AML, and rarely the presenting sign of undiagnosed
      CML or aleukemic leukemia. Paraplegia due to a spinal cord GS is an extremely
      rare presentation of undiagnosed leukemia. This is the first case report of
      paraplegia as the presenting manifestation of extramedullary megakaryoblastic
      transformation of previously undiagnosed CML. A 53-year-old woman reported back
      pain for 6 days, rapidly progressing to paraplegia. Physical examination noted a
      large abdominal mass and flaccid paralysis in both lower extremities. Spinal MRI
      revealed a T4-T6 vertebral mass causing spinal stenosis and cord compression.
      Tumor debulking and laminectomy were performed emergently. The tumor consisted of
      noncohesive blast cells. The CBC revealed a leukocyte count of 238,300/microl and
      a differential consistent with CML. Reexamination of the patient found that the
      abdominal mass was a giant spleen. Further immunohistochemical studies of the
      tumor were consistent with extramedullary acute megakaryoblastic blast
      transformation of CML. Although extramedullary blast crises herald the
      accelerated phases in approximately 10% of CML cases, megakaryoblastic blast
      transformation of CML accounts for less than 3% of these cases. The combination
      of acute paraplegia and megakaryoblastic transformation in a previously
      undiagnosed patient with CML is extremely rare and may pose a diagnostic dilemma.

PMID- 17019693
TI  - GSNO attenuates EAE disease by S-nitrosylation-mediated modulation of endothelial
      monocyte interactions.
AB  - S-Nitrosoglutathione (GSNO) is an endogenous nitric oxide carrier and recently,
      has been documented for its anti-inflammatory effects in rat model of cerebral
      ischemia (Khan et al. (2005) J Cereb Blood Flow Metab 25:177-192). Here, we
      explored the neuroprotective effects mediated by GSNO in Lewis rat model of EAE
      and its mechanism of action using in vitro model of monocyte-endothelial cell
      interaction. Oral administration of GSNO attenuated the clinical disease course
      in EAE animals by inhibiting the infiltration of vascular immune cells in the CNS
      that subsequently led to the reduction in the expression of proinflammatory
      cytokines and consequently limited demyelination. Based on the inhibition in
      infiltration of immune cells, we hypothesized that GSNO modulated endothelial
      cell activation that led to reduce cellular infiltration in the CNS. Using an in
      vitro model, we established that GSNO inhibited monocyte adhesion to the
      activated endothelial cell, which was mediated by down regulation of endothelial
      cell adhesion molecules (CAMs). The mechanism by which GSNO modulated CAMs
      expression appeared to be via S-nitrosylation of p65, which consequently
      inhibited nuclear factor kappa B (NF-kappaB) activation in endothelial cells.
      These observations suggest that GSNO exerts its protective effects in EAE by
      inhibition of cellular infiltration into the CNS by S-nitrosylation of p65,
      thereby modulating NF-kappaB-CAMs pathway in endothelial cells.

PMID- 17019694
TI  - Effect of estradiol and progesterone on thyroid gland in pigs: a histochemical,
      stereological, and ultrastructural study.
AB  - The cellular and subcellular organization of thyroid follicular cells in
      peripubertal (6-month-old) male pigs treated with estradiol-dipropionate (Oe)
      plus progesterone (Pr) in combination on the first postnatal day was studied. A
      stereological method was used for morphometric determinations of the relative
      volume densities of the follicular epithelium, colloid and interstitium, and for
      establishing the epithelial height and index of activation rate. Statistically
      significant differences of the examined parameters between the control and Oe+Pr 
      treated groups were determined by Student's t-test. The subcellular organization
      of thyroid follicular cells was studied using transmission electron microscopy
      (TEM). When compared with the control group, in the Oe+Pr -treated pigs, thyroid
      follicles possessed a noticeably higher follicular epithelium when compared with
      the control animals. The observed changes were quantified and comparison between
      the experimental groups showed that the height, volume density of follicular
      epithelium, and index of activation rate were significantly (P < 0.05) increased,
      whereas the relative volume density of the colloid was significantly (P < 0.05)
      decreased. At the subcellular level the thyroid follicular cells of Oe+Pr 
      treated pigs were characterized by increased number of polysomes and dense bodies
      and extensive endoplasmatic reticulum. It was concluded that a single neonatal
      treatment with female gonadal steroids exerted a prolonged effect on the pig's
      thyroid, characterized by increased biosynthesis and reabsorption of the colloid
      by the follicular cells.

PMID- 17019695
TI  - Electron microscopic study of novel threadlike structures on the surfaces of
      mammalian organs.
AB  - The ultrastructures of novel threadlike structures (NTSs) and corpuscles on the
      surfaces of internal organs of rats were investigated using electron microscopy.
      The samples were studied in situ by using a stereomicroscope and were taken for
      further morphological analysis. Scanning electron microscope (SEM) images
      revealed a bundle structure of threadlike tissue, which was composed of several
      10-micro m-thick subducts. The surfaces of the corpuscles were rather coarse and
      fenestrated. The corpuscles had cucumber-like shapes with an average length of
      about 2 mm and a thickness of about 400 micro m. Transmission electron microscope
      (TEM) images disclosed disordered collagen fibers, which formed the extracellular
      matrix of the threadlike tissue, and immune-function cells, like macrophages,
      mast cells, and eosinophils. Sinuses of various diameters, which were thought to
      be cross-sections of the lumens of the subducts, were observed in the TEM, cryo
      SEM and focused-ion-beam SEM images. These SEM images were obtained for the first
      time to reveal the detailed structure of the NTSs that were only recently
      discovered.

PMID- 17019696
TI  - Collagen types I, III, and V constitute the thick collagen fibrils of the mouse
      decidua.
AB  - A mammal's endometrium is deeply remodeled while receiving and implanting an
      embryo. In addition to cell proliferation and growth, endometrial remodeling also
      comprises synthesis and degradation of several molecular components of the
      extracellular matrix. All of these events are orchestrated by a precise sequence
      of ovarian hormones and influenced by several types of cytokines. As we have
      previously reported, an intriguing and rapid increase in collagen fibril diameter
      occurs in the decidualized areas of the endometrium, surrounding the implantation
      crypt, whereas collagen fibrils situated far from the embryo remain unchanged.
      Collagen fibrilogenesis is a complex molecular process coordinated by a number of
      factors, such as the types and amounts of glycosaminoglycans and proteoglycans
      associated with collagen molecules. Collagen genetic type, mechanical stress,
      aging, and other factors not yet identified also contribute to this development.
      A recent study suggests that thick fibrils from mouse decidua are formed, at
      least in part, by aggregation of thin fibrils existing in the stroma before the
      onset of decidualization. In the present ultrastructural study using single and
      double immunogold localization, we showed that both thin and thick collagen
      fibrils present in the mouse pregnant endometrium endometrium are heterotypic
      structures formed at least by type I, type III, and type V collagens. However,
      type V collagen predominates in the thick collagen fibrils, whereas it is almost
      absent of the thin collagen fibrils. The putative role of type V homotrimer in
      the rapid increase of the diameter of collagen fibrils of the mouse decidua is
      discussed.

PMID- 17019697
TI  - Aggregating the amyloid Abeta(11-25) peptide into a four-stranded beta-sheet
      structure.
AB  - We present a detailed analysis of the structural properties of one monomer of
      Abeta(11-25) as well as of the aggregation mechanisms for four chains of Abeta(11
      25) using the activation-relaxation technique coupled with a generic energy
      potential. Starting from a random distribution of these four chains, we find that
      the system assembles rapidly into a random globular state that evolves into three
      and four-stranded antiparallel beta-sheets. The aggregation process is
      considerably accelerated by the presence of preformed dimers. We also find that
      the reptation mechanism already identified in shorter peptides plays a
      significant role here in allowing the structure to reorganize without having to
      fully dissociate.

PMID- 17019698
TI  - Crystal structures of E. coli CcmG and its mutants reveal key roles of the N
      terminal beta-sheet and the fingerprint region.
AB  - CcmG, also designated DsbE, functions as a periplasmic protein thiol:disulfide
      oxidoreductase and is required for cytochrome c maturation. Here we report the
      crystal structures of Escherichia coli CcmG and its two mutants, P144A and the N
      terminal fifty seven-residue deletion mutant, and two additional deletion mutants
      were studied by circular dichroism. Structural comparison of E. coli CcmG with
      its deletion mutants reveals that the N-terminal beta-sheet is essential for
      maintaining the folding topology and consequently maintaining the active-site
      structure of CcmG. Pro144 and Glu145 are key residues of the fingerprint region
      of CcmG. Pro144 is in cis-configuration, and it makes van der Waals interactions
      with the active-site disulfide Cys80-Cys83 and forms a C--H...O hydrogen bond
      with Thr82, helping stabilize the active-site structure. Glu145 forms a salt
      bridge and hydrogen-bond network with other residues of the fingerprint region
      and with Arg158, further stabilizing the active-site structure. The cis
      configuration of Pro144 makes the backbone nitrogen and oxygen of Ala143 exposed
      to solvent, favorable for interacting with binding partners. The key role of cis
      Pro144 is verified by the P144A mutant, which contains trans-Ala144 and displays
      redox property changes. Structural comparison of E. coli CcmG with the recently
      reported structure of CcmG in complex with the N-terminal domain of DsbD reveals
      that Tyr141 undergoes conformational changes upon binding DsbD. A cis-proline
      located at the N-terminus of the first beta-strand of the betabetaalpha motif of
      the thioredoxin-like domain is a conserved structural feature of the thioredoxin
      superfamily.

PMID- 17019700
TI  - Flagellar apparatus of south-seeking many-celled magnetotactic prokaryotes.
AB  - Magnetotactic bacteria orient and migrate along geomagnetic field lines. Each
      cell contains membrane-enclosed, nano-scale, iron-mineral particles called
      magnetosomes that cause alignment of the cell in the geomagnetic field as the
      bacteria swim propelled by flagella. In this work we studied the ultrastructure
      of the flagellar apparatus in many-celled magnetotactic prokaryotes (MMP) that
      consist of several Gram-negative cells arranged radially around an acellular
      compartment. Flagella covered the organism surface, and were observed exclusively
      at the portion of each cell that faced the environment. The flagella were helical
      tubes never as long as a complete turn of the helix. Flagellar filaments varied
      in length from 0.9 to 3.8 micro m (average 2.4 +/- 0.5 micro m, n = 150) and in
      width from 12.0 to 19.5 nm (average 15.9 +/- 1.4 nm, n = 52), which is different
      from previous reports for similar microorganisms. At the base of the flagella, a
      curved hook structure slightly thicker than the flagellar filaments was observed.
      In freeze-fractured samples, macromolecular complexes about 50 nm in diameter,
      which possibly corresponded to part of the flagella basal body, were observed in
      both the P-face of the cytoplasmic membrane and the E-face of the outer membrane.
      Transmission electron microscopy showed that magnetosomes occurred in planar
      groups in the cytoplasm close and parallel to the organism surface. A striated
      structure, which could be involved in maintaining magnetosomes fixed in the cell,
      was usually observed running along magnetosome chains. The coordinated movement
      of the MMP depends on the interaction between the flagella of each cell with the
      flagella of adjacent cells of the microorganism.

PMID- 17019699
TI  - Ischemia leads to delayed union during fracture healing: a mouse model.
AB  - Vascular damage accompanying skeletal injury leads to an ischemic environment,
      and in clinical settings the extent of vascular damage is directly correlated
      with failure of skeletal repair. However, the exact mechanism(s) underlying
      ischemia-related defects in bone healing are not well understood. To better
      understand the mechanism and to facilitate development of novel interventions to
      treat ischemic fractures, a mouse model of long bone fracture healing in an
      ischemic environment was created. Ischemia was induced by femoral artery
      resection prior to tibia fracture. Fractures were left unstabilized or were
      stabilized with custom-designed external fixators. Animals with intact femoral
      vessels served as controls. Tissues from non-stabilized fractures were analyzed
      at various times from 3 to 28 days after injury (n = 5/time point). Femoral
      artery resection severely impaired blood supply to the fractured limbs, and
      perfusion to the fracture sites did not recover until 14 days post-injury.
      Ischemia significantly decreased the callus size (p < 0.05), and decreased bone
      (p < 0.05) and cartilage (p < 0.05) matrix production during healing of non
      stabilized fracture. The decreased formation of skeletal tissues in ischemic
      limbs was accompanied by decreased cell proliferation and increased apoptosis at
      early time points, and increased fibrous and fatty tissues adjacent to the
      fracture site during the third and fourth week after injury. These alterations
      led to a delayed-union. Complete fracture healing was not achieved in the
      majority (day 21 = 4/5; day 28 = 5/5) of ischemic animals, while all control mice
      (n = 5/5) had evidence of bony bridging by day 21. The ratio of cartilage to bone
      was similar in ischemic and control limbs at days 7 and 10 in non-stabilized
      fractures. In stabilized fractures, which healed through direct bone formation in
      the nonischemic controls, ischemia decreased the amount of bone formation at days
      10 and 14 (n = 5/time point) but did not induce cartilage formation. These data
      reveal that an ischemic insult in the hind limb prior to fracture leads to a
      delayed union or a nonunion, but does not favor formation of cartilage over bone.
      This model will be useful for testing novel therapeutic regimens to stimulate
      fracture healing.

PMID- 17019701
TI  - Nonidentical and outlier duty cycles as factors accelerating UHMWPE wear in THA:
      a finite element exploration.
AB  - Wear rate and wear direction vary considerably within total hip arthroplasty
      (THA) patient cohorts. Third body effects and wide-ranging differences in patient
      activity levels are two factors suspected of contributing to wear variability. A
      sliding-distance-coupled contact finite element formulation was used to test the
      hypothesis that nonidentical duty cycles (differing activities, or change of
      third body challenge) produce accelerations in polyethylene wear. Effects of
      nonidentical duty cycles, time-variant femoral head roughening, and outlier gait
      inputs were investigated. Without femoral head roughening, combination walk/stair
      climb wear simulations did not result in appreciably higher volumetric wear than
      a walk-only simulation, but when a roughened zone was included, walk/stair-climb
      volumetric wear increased by approximately 57% above that of a similarly
      roughened walk-only simulation. To investigate time-variant femoral head
      roughening, wear simulations were begun with femoral head roughening at one
      location on the femoral head, switching to another location halfway through the
      simulation. Results varied depending on roughening sites, but cases of
      substantial increase in wear involved a transient jump in wear rate shortly after
      the change of head roughening location. Outlier duty cycles were simulated by
      increasing or decreasing the joint contact force and range of motion inputs, to
      levels at the 97.5th and 2.5th percentiles of a population of normal subjects.
      The resulting wear showed an increase or decrease closely proportional to the
      percentage by which each input (force or range of motion) was changed.

PMID- 17019702
TI  - Center of mass motion and the effects of ankle bracing on metabolic cost during
      submaximal walking trials.
AB  - The goal of this research was to examine the relationship between center of mass
      (CoM) motion and metabolic cost and to assess secondarily the effects of equinus
      gait on metabolic cost during walking trials at various velocities. Twelve (n=12)
      healthy male adults walked in four brace conditions, including fixed equinus, at
      three different walking speeds. Metabolic measures and 3D kinematic data were
      collected during each trial. Significant main effects for velocity were observed
      on both dependent measures, net O2 cost (p<0.001), and CoM vertical excursion
      (CoMz) (p<0.01). Correlation analysis showed significant positive correlations
      between net O2 cost and CoMz that were strongest at fast velocities. Further,
      analysis revealed the cost of walking at a comfortable speed in the equine
      position was 28% greater than walking in braces without springs or springs in
      neutral position and 64% greater than walking in shoes alone. CoMz does correlate
      with metabolic cost as measured by net O2 cost. Also, normal subjects walking in
      equinus have an increased net O2 cost and increased CoMz when compared to walking
      with shoes alone or the other brace conditions at all velocities.

PMID- 17019703
TI  - Current analytical methods for the detection of dityrosine, a biomarker of
      oxidative stress, in biological samples.
AB  - Dityrosine is a fluorescent molecule formed as a result of normal
      posttranslational processing. In many structural proteins, dityrosine confers
      resistance to proteolysis and physicochemical trauma as a stabilizing crosslink.
      Dityrosine has also been found in oxidative/nitrative stress under a variety of
      conditions and biological systems. In this regard, it has been used as an
      important biomarker for oxidatively modified proteins during UV and gamma
      irradiation, aging, and exposure to oxygen free radicals, nitrogen dioxide,
      peroxynitrite, and lipid hydroperoxides. Renewed interest in dityrosine and other
      tyrosine oxidation products as clinical indicators of oxidative modification has
      driven the development of important techniques for the specific analysis and
      quantification of these molecules. The presence of elevated levels of dityrosine
      in mammalian tissue and urine samples has been measured by chromatographic
      separation followed by mass spectrometry GC-MS and HPLC-MS/MS. Increases in
      dityrosine levels have been associated with pathologies such as eye cataracts,
      atherosclerosis, acute inflammation, and Alzheimer's disease. The continued
      development of, and increased accessibility to, improved mass spectrometric
      instrumentation will expand the capability, feasibility, and sensitivity with
      which specific biomarkers like dityrosine can be measured.

PMID- 17019704
TI  - New insights into DHFR interactions: analysis of Pneumocystis carinii and mouse
      DHFR complexes with NADPH and two highly potent 5-(omega-carboxy(alkyloxy)
      trimethoprim derivatives reveals conformational correlations with activity and
      novel parallel ring stacking interactions.
AB  - Structural data are reported for two highly potent antifolates, 2,4-diamino-5
      [3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)]benzylpyrimidine (PY1011), with 5000
      fold selectivity for Pneumocystis carinii dihydrofolate reductase (pcDHFR),
      relative to rat liver DHFR, and 2,4-diamino-5-[2-methoxy-5-(4
      carboxybutyloxy)benzyl]pyrimidine (PY957), that has 80-fold selectivity for
      pcDHFR. Crystal structures are reported for NADPH ternary complexes with PY957
      and pcDHFR, refined to 2.2 A resolution; with PY1011 and pcDHFR, refined to 2.0 A
      resolution; and with PY1011 and mouse DHFR (mDHFR), refined to 2.2 A resolution.
      These results reveal that the carboxylate of the omega-carboxyalkyloxy side chain
      of these inhibitors form ionic interactions with the conserved Arg in the
      substrate binding pocket of DHFR. These data suggest that the enhanced inhibitory
      activity of PY1011 compared with PY957 is, in part, due to the favorable contacts
      with Phe69 of pcDHFR by the methylene carbons of the inhibitor side chain that
      are oriented by the triple bond of the 1-pentynyl side chain. These contacts are
      not present in the PY957 pcDHFR complex, or in the PY1011 mDHFR complex. In the
      structure of mDHFR the site of Phe69 in pcDHFR is occupied by Asn64. These data
      also revealed a preference for an unusual parallel ring stacking interaction
      between Tyr35 of the active site helix and Phe199 of the C-terminal beta sheet in
      pcDHFR and by Tyr33 and Phe179 in mDHFR that is independent of bound ligand. A
      unique His174-His187 parallel ring stacking interaction was also observed only in
      the structure of pcDHFR. These ring stacking interactions are rarely found in any
      other protein families and may serve to enhance protein stability.

PMID- 17019706
TI  - Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya.
AB  - Endemic Burkitt's lymphoma (eBL), the most common childhood cancer in sub-Saharan
      Africa, occurs at a high incidence in western Kenya, a region that also
      experiences holoendemic malaria. Holoendemic malaria has been identified as a co
      factor in the etiology of this cancer. We hypothesized that eBL may cluster
      spatially within this region. Medical records for all eBL cases diagnosed from
      1999 through 2004 at Nyanza Provincial General Hospital were reviewed for case
      residential information to examine this hypothesis. Two cluster detection
      methods, Anselin's Local Moran test for spatial autocorrelation and a spatial
      scan test statistic, were applied to this residential data to determine whether
      statistically significant high- and low-risk areas were present in the Province.
      During the 6-year study period, 272 children were diagnosed with eBL, with an
      average annual incidence of 2.15 cases per 100,000 children. Using Empirical
      Bayes smoothed rates, the Local Moran test identified 1 large multi-centered area
      of low eBL risk (p-values < 0.01) and 2 significant multi-centered clusters of
      high eBL risk (p-values < 0.001). The spatial scan detected 3 small independent
      low-risk areas (p-values < 0.02) and 2 high-risk clusters (p-values = 0.001),
      both similar in location to those identified from the Local Moran analysis.
      Significant spatial clustering of elevated eBL risk in high-malaria transmission
      regions and of reduced incidence where malaria is infrequent suggests that
      malaria plays a role in the complex eBL etiology, but that additional factors are
      also likely involved.

PMID- 17019705
TI  - Medical history, cigarette smoking and risk of acoustic neuroma: an international
      case-control study.
AB  - Acoustic neuroma (vestibular schwannoma) is a benign tumor of the
      vestibulocochlear nerve. Its recorded incidence is increasing but risk factors
      for this tumor have scarcely been investigated. We conducted a population-based
      case-control study of risk factors for acoustic neuroma in the UK and Nordic
      countries, including 563 cases and 2,703 controls. Tumor risk was analyzed in
      relation to medical history and cigarette smoking. Risk of acoustic neuroma was
      significantly raised in parous compared with nulliparous women (OR = 1.7, 95% CI:
      1.1-2.6), but was not related to age at first birth or number of children. Risk
      was not associated with a history of allergic disease, past head injury, past
      diagnosis of a neoplasm or birth characteristics, but was significantly raised
      for past diagnosis of epilepsy (OR = 2.5, 95% CI: 1.3-4.9). Tumor risk was
      significantly reduced in subjects who had ever regularly smoked cigarettes (OR =
      0.7, 95% CI: 0.6-0.9), but the reduction applied only to current smokers (OR =
      0.5, 95% CI: 0.4-0.6), not ex-smokers (OR = 1.0, 95% CI: 0.8-1.3). The reduced
      risk of acoustic neuroma in smokers and raised risk in parous women might relate
      to sex hormone levels, or smoking might suppress tumor growth, but effects of
      parity and smoking on timing of diagnosis of the tumor are also a potential
      explanation. The raised risk in relation to past diagnosis of epilepsy might be a
      surveillance artefact or imply that epilepsy and/or antiepileptic medication use
      predispose to acoustic neuroma. These findings need replication by other studies
      and possible mechanisms need to be clarified.

PMID- 17019707
TI  - Annexin-I as a potential target for green tea extract induced actin remodeling.
AB  - Using a multistep human urothelial model, we previously showed that green tea
      extract (GTE) selectively modulates actin remodeling in transformed cells (MC
      T11), which resulted in increased cell adhesion and reduced cell motility (Lu et
      al., Clin Cancer Res 2005;11:1675-83). This study further analyzed which actin
      binding proteins (ABPs) might be involved in this process. Proteomic profiles of
      GTE treated and untreated MC-T11 cells using two-dimensional gel electrophoresis
      coupled with liquid chromatography tandem mass spectrometry (LC/MS/MS) and matrix
      assisted laser desorption and ionization time-of-flight (MALDI-TOF) identified 20
      GTE-induced proteins. Among them, 3 were ABPs (tropomodulin, cofilin and annexin
      I), and only annexin-I showed a dose- and time-dependent expression. The
      increased annexin-I correlated with actin remodeling, and was the result of
      transcription level up-regulation, as determined by RT-PCR, pull-down immunoblot
      and siRNA analyses. 5-Azacytidine, a DNA methylation inhibitor, exhibited no
      effect on annexin-I expression when used alone, but had an additive effect for
      GTE-induced annexin-I expression. Immunohistochemistry of bladder cancer tissue
      array showed a decrease of annexin-I expression in carcinoma in situ and low
      grade papillary carcinoma (n = 32, 0% positive) compared to nontumor urothelium
      (n = 18, 89% positive) (p < 0.001 by Fisher exact test), but increased in some (6
      of 15, 40%) high-grade tumors. Together, GTE induced annexin-I expression plays a
      role in regulating actin remodeling and decreased annexin-I expression is a
      common event in early stage of bladder cancer development.

PMID- 17019708
TI  - Inhibition of carcinoma cell-derived VEGF reduces inflammatory characteristics in
      xenograft carcinoma.
AB  - The stroma of carcinomas shares several characteristics with inflamed tissues
      including a distorted vasculature, active angiogenesis and macrophage
      infiltration. In addition, the tumor interstitial fluid pressure (P(IF)) of the
      stroma is pathologically elevated. We show here that bevacizumab [rhuMab vascular
      endothelial growth factor (VEGF), Avastin], a monoclonal antibody to VEGF, at a
      dose of 5 mg/kg modulated inflammation in KAT-4 xenograft human anaplastic
      thyroid carcinoma tissue. At this dose, bevacizumab reduced the density of
      macrophages, MHC class II antigen expression by macrophages and IL-1beta mRNA
      expression. Furthermore, bevacizumab lowered tumor extracellular fluid volume,
      plasma protein leakage from tumor vessels, the number of CD31-positive structures
      and tumor P(IF). The tumor plasma volume and the number of alpha-smooth muscle
      actin-positive vessels, however, remained unchanged. Our data suggest that
      carcinoma cell-derived VEGF either directly or indirectly participates in
      maintaining an inflammatory microenvironment in experimental KAT-4 carcinoma.
      Furthermore, our data indicate that the reduction of inflammation resulting in
      reduced vascular permeability and decrease in the tumor extracellular fluid
      volume by bevacizumab contributes to reduced tumor P(IF).

PMID- 17019709
TI  - Ataxia-telangiectasia mutated expression is associated with tobacco smoke
      exposure in esophageal cancer tissues and benzo[a]pyrene diol epoxide in cell
      lines.
AB  - Esophageal cancer is a substantial health problem because of its usually late
      stage at diagnosis and poor prognosis. Tobacco smoking and alcohol use are the
      most important risk factors in the development of esophageal squamous cell
      carcinoma (SCC). Our previous study demonstrated the binding of benzo[a]pyrene
      diol epoxide (BPDE), a carcinogen present in tobacco smoke and environmental
      pollution, to the ataxia-telangiectasia mutated (ATM) gene. To understand how
      this binding affects the alteration of ATM expression and to identify biomarkers
      for the detection of esophageal cancer, we analyzed ATM mRNA expression in tissue
      specimens from patients with esophageal SCC and premalignant lesions using in
      situ hybridization. We then performed in vitro experiments to verify and extend
      our ex vivo observations. We found that ATM expression was increased in
      esophageal SCC and its premalignant lesions when compared with normal tissues and
      that increased ATM expression was associated with tobacco smoke exposure and
      tumor de-differentiation. Moreover, BPDE induced ATM expression in esophageal SCC
      cell lines in a time-dependent manner. In summary, the BPDE in tobacco smoke may
      be responsible for increased ATM expression in premalignant and malignant
      esophageal tissues. Our findings suggest that the ATM gene should be further
      evaluated as a biomarker for the early detection of esophageal cancer and tobacco
      use in patients.

PMID- 17019710
TI  - Cancer-germline gene expression in pediatric solid tumors using quantitative real
      time PCR.
AB  - Cancer-germline genes (CGGs) code for immunogenic antigens that are present on
      various human tumors but not on normal tissues. The importance of CGGs in cancer
      immunotherapy has led to detailed studies of their expression in a range of human
      tumors. We measured the levels of expression of 12 CGGs in various pediatric
      solid tumors to identify targets for therapeutic cancer vaccines. Quantitative
      real-time PCR (qPCR) was used to measure the expression of 8 MAGE genes and of
      genes LAGE-2/NY-ESO-1 and GAGE-1, 2, 8 in 9 osteosarcomas, 10 neuroblastomas, 12
      rhabdomyosarcomas and 18 Ewing's sarcomas. Nine tumors were also examined by
      immunohistochemistry with monoclonal antibodies specific for the MAGE-A1, MAGE-A4
      and NY-ESO-1 proteins. All osteosarcoma and 80% of neuroblastoma samples
      expressed several CGGs at high levels. Six of 12 rhabdomyosarcomas and 11 of 18
      Ewing's sarcomas expressed at least one CGG. Immunohistochemistry data correlated
      well with qPCR results and showed a homogeneous protein distribution pattern in
      most positive tumors. No correlation was found between the levels of CGG
      expression in the tumors and clinicopathological parameters of the patients.
      Pediatric solid tumors express several CGGs, which encode antigens that could be
      targeted in therapeutic vaccination trials. Several CGGs of the MAGE, GAGE and
      LAGE families are coexpressed in a large proportion of osteosarcoma and
      neuroblastoma samples. Some rhabdomyosarcomas express several of these genes at
      high levels. Ewing's sarcomas have an overall low CGG expression.

PMID- 17019711
TI  - Epigenetic modulation of endogenous tumor suppressor expression in lung cancer
      xenografts suppresses tumorigenicity.
AB  - Epigenetic changes involved in cancer development, unlike genetic changes, are
      reversible. DNA methyltransferase and histone deacetylase inhibitors show
      antiproliferative effects in vitro, through tumor suppressor reactivation and
      induction of apoptosis. Such inhibitors have shown activity in the treatment of
      hematologic disorders but there is little data concerning their effectiveness in
      treatment of solid tumors. FHIT, WWOX and other tumor suppressor genes are
      frequently epigenetically inactivated in lung cancers. Lung cancer cell clones
      carrying conditional FHIT or WWOX transgenes showed significant suppression of
      xenograft tumor growth after induction of expression of the FHIT or WWOX
      transgene, suggesting that treatments to restore endogenous Fhit and Wwox
      expression in lung cancers would result in decreased tumorigenicity. H1299 lung
      cancer cells, lacking Fhit, Wwox, p16(INK4a) and Rassf1a expression due to
      epigenetic modifications, were used to assess efficacy of epigenetically targeted
      protocols in suppressing growth of lung tumors, by injection of 5-aza-2
      deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299
      tumors. High doses of intraperitoneal AZA/TSA suppressed growth of small tumors
      but did not affect large tumors (200 mm(3)); lower AZA doses, administered
      intraperitoneally or intratumorally, suppressed growth of small tumors without
      apparent toxicity. Responding tumors showed restoration of Fhit, Wwox, p16(INKa),
      Rassf1a expression, low mitotic activity, high apoptotic fraction and activation
      of caspase 3. These preclinical studies show the therapeutic potential of
      restoration of tumor suppressor expression through epigenetic modulation and the
      promise of re-expressed tumor suppressors as markers and effectors of the
      responses.

PMID- 17019712
TI  - Identification and meta-analysis of a small gene expression signature for the
      diagnosis of estrogen receptor status in invasive ductal breast cancer.
AB  - In breast cancer, the determination of estrogen receptor (ER) expression is
      crucial for the decision on therapeutic strategies. Current ER expression
      analysis is based on immunohistochemical (IHC) staining of ER on formalin fixed
      tissue sections. However, low levels of ER expression frequently escape detection
      because of varying sensitivities of routine histopathological laboratories.
      Moreover, in estimating ER by IHC the receptor protein only is tested instead of
      the complex underlying ER pathway, which reflects its biological activity. To
      overcome this limitation, we have used the microarray technology to study 56
      samples of invasive ductal carcinoma. We infer a robust and reliable signature of
      10 genes, which is associated with ER expression and presumably therapeutically
      relevant biological processes. In a meta-analysis, the signature was tested on 3
      further independent microarray gene expression data sets, covering different
      laboratories, array platforms, and clinics. The classification based on the
      signature showed a very low misclassification rate. In summary, the expression of
      few genes is sufficient to determine ER status. Future decisions on antiestrogen
      based therapy in breast cancer could be based on this signature rather than on
      immunostaining alone.

PMID- 17019713
TI  - Ursodeoxycholic acid modulates histone acetylation and induces differentiation
      and senescence.
AB  - Agents that can modulate colonic environment and control dysregulated signaling
      are being evaluated for their chemopreventive potential in colon cancer.
      Ursodeoxycholate (UDCA) has shown chemopreventive potential in preclinical and
      animal models of colon cancer, but the mechanism behind it remains unknown. Here
      biological effects of UDCA were examined to understand mechanism behind its
      chemoprevention in colon cancer. Our data suggests that UDCA can suppress growth
      in a wide variety of cancer cell lines and can induce low level of apoptosis in
      colon cancer cells. We also found that UDCA treatment induces alteration in
      morphology, increased cell size, upregulation of cytokeratin 8, 18 and 19 and E
      cadherin, cytokeratin remodeling and accumulation of lipid droplets, suggesting
      that UDCA induces differentiation in colon carcinoma cells. Our results also
      suggest significant differences in UDCA and sodium butyrate induced functional
      differentiation. We also report for the first time that UDCA can induce
      senescence in colon cancer cells as assessed by flattened, spread out and
      vacuolated morphology as well as by senescence marker beta-galactosidase
      staining. We also found that UDCA inhibits the telomerase activity. Surprisingly,
      we found that UDCA is not a histone deacytylase inhibitor but instead induces
      hypoacetylation of histones unlike hyperacetylation induced by sodium butyrate.
      Our results also suggest that, although UDCA induced senescence is p53, p21 and
      Rb independent, HDAC6 appears to be important in UDCA induced senescence. In
      summary, our data shows that UDCA modulates chromatin by inducing histone
      hypoacetylation and induces differentiation and senescence in colon cancer cells.

PMID- 17019714
TI  - Pentose phosphate cycle oxidative and nonoxidative balance: A new vulnerable
      target for overcoming drug resistance in cancer.
AB  - The metabolic network of cancer cells confers adaptive mechanisms against many
      chemotherapeutic agents, but also presents critical constraints that make the
      cells vulnerable to perturbation of the network due to drug therapy. To identify
      these fragilities, combination therapies based on targeting the nucleic acid
      synthesis metabolic network at multiple points were tested. Results showed that
      cancer cells overcome single hit strategies through different metabolic network
      adaptations, demonstrating the robustness of cancer cell metabolism. Analysis of
      these adaptations also identified the maintenance of pentose phosphate cycle
      oxidative and nonoxidative balance to be critical for cancer cell survival and
      vulnerable to chemotherapeutic intervention. The vulnerability of cancer cells to
      the imbalance on pentose phosphate cycle was demonstrated by phenotypic phase
      plane analysis.

PMID- 17019715
TI  - Selective Chk1 inhibitors differentially sensitize p53-deficient cancer cells to
      cancer therapeutics.
AB  - The majority of cancer therapeutics induces DNA damage to kill cells. Normal
      proliferating cells undergo cell cycle arrest in response to DNA damage, thus
      allowing DNA repair to protect the genome. DNA damage induced cell cycle arrest
      depends on an evolutionarily conserved signal transduction network in which the
      Chk1 kinase plays a critical role. In mammalian cells, the p53 and RB pathways
      further augment the cell cycle arrest response to prevent catastrophic cell
      death. Given the fact that most tumor cells suffer defects in the p53 and RB
      pathways, it is likely that tumor cells would depend more on the Chk1 kinase to
      maintain cell cycle arrest than would normal cells. Therefore Chk1 inhibition
      could be used to specifically sensitize tumor cells to DNA-damaging agents. We
      have previously shown that siRNA-mediated Chk1 knockdown abrogates DNA damage
      induced checkpoints and potentiates the cytotoxicity of several DNA-damaging
      agents in p53-deficient cell lines. In this study, we have developed 2 potent and
      selective Chk1 inhibitors, A-690002 and A-641397, and shown that these compounds
      abrogate cell cycle checkpoints and potentiate the cytotoxicity of topoisomerase
      inhibitors and gamma-radiation in p53-deficient but not in p53-proficient cells
      of different tissue origins. These results indicate that it is feasible to
      achieve a therapeutic window with 1 or more Chk1 inhibitors in potentiation of
      cancer therapy based on the status of the p53 pathway in a wide spectrum of tumor
      types.

PMID- 17019716
TI  - Dietary intake of calcium, fiber and other micronutrients in relation to
      colorectal cancer risk: Results from the Shanghai Women's Health Study.
AB  - We evaluated the associations of dietary intake of calcium, fiber and vitamins
      with colorectal cancer risk in a population-based prospective cohort study
      conducted among Chinese women in Shanghai. Subjects were recruited in urban
      Shanghai from March 1997 to May 2000. All subjects were interviewed in-person to
      obtain information on demographic and lifestyle factors and anthropometric
      measurement was conducted. Usual dietary intake, using a validated food frequency
      questionnaire was assessed at the baseline survey. After following a total of
      73,314 women for a median of 5.74 years, 283 incident colorectal cancer cases
      were recorded. Excluding the first 2 years of follow-up, a high intake of calcium
      was associated with a decreased risk of colorectal cancer. Comparing the highest
      quintile of nutrients intake to the lowest, the adjusted relative risk for
      colorectal cancer was 0.6 (p value for trend = 0.023) for calcium. No apparent
      associations were found for fiber, total vitamin A, carotene, vitamins B1, B2,
      B3, C and E with colorectal cancer risk. Our results suggest that calcium may be
      protective against colorectal cancer development even at a lower consumption
      level compared to Western populations.

PMID- 17019717
TI  - Recreational physical activity and risk of prostate cancer: A prospective
      population-based study in Norway (the HUNT study).
AB  - Physical activity has been studied in relation to prostate cancer risk, but the
      findings have been inconclusive. We prospectively examined the association
      between self-reported recreational physical activity and overall risk of prostate
      cancer, risk of advanced disease and risk of prostate cancer death in a cohort of
      29,110 Norwegian men. Incident prostate cancers were obtained from the Norwegian
      Cancer Registry, and prostate cancer deaths were obtained from the national Cause
      of Death Registry. During 17 years of follow-up, 957 incident cases were
      identified, 266 of them were advanced (i.e. metastases at diagnosis) and 354 of
      the incident cases died from prostate cancer. In multivariable analysis,
      frequency and duration of exercise were inversely associated with the risk of
      advanced prostate cancer (p for trend = 0.04 and 0.02). We computed a summary
      score that combined frequency, duration and intensity of exercise, and this score
      showed inverse associations with advanced prostate cancer risk and mortality (p
      for trend = 0.02 and 0.07). Compared to men who reported no activity, the
      relative risks (95% confidence intervals) among men in the highest category of
      physical exercise was 0.64 (0.43-0.95) for advanced prostate cancer and 0.67
      (0.48-0.94) for prostate cancer death. We found no association between physical
      activity and overall risk of prostate cancer. We conclude that recreational
      physical exercise is associated with reduced risk of advanced prostate cancer and
      prostate cancer death.

PMID- 17019718
TI  - Photochemoprevention of UVB-induced skin carcinogenesis in SKH-1 mice by brown
      algae polyphenols.
AB  - Chronic exposure of the skin to ultraviolet B (UVB) radiation induces oxidative
      stress, which plays a crucial role in the induction of skin cancer. In this
      study, the effect of dietary feeding and topical application of brown algae
      polyphenols on UVB radiation-induced skin carcinogenesis in SKH-1 mice was
      investigated. SKH-1 hairless mice were randomly divided into 9 groups, including
      control, UVB control and treatment groups. They were treated orally (0.1% and
      0.5% with AIN-76 diet, w/w) and topically (3 and 6 mg/0.2 ml of vehicle) with
      brown algae polyphenols and irradiated with UVB for 26 weeks. Dietary feeding
      (0.1% and 0.5%) of brown algae polyphenols significantly reduced tumor
      multiplicity (45% and 56%) and tumor volume (54% and 65%), and topical
      administration (3 and 6 mg) significantly decreased tumor multiplicity (60% and
      46%) and tumor volume (66% and 57%), respectively, per tumor-bearing mouse.
      Dietary feeding and topical administration of the polyphenols also inhibited
      tumor incidence by 6% and 21%, respectively, but the results were not
      significant. Dietary and topical administration of the polyphenols markedly
      inhibited cyclooxygenase-2 activity and cell proliferation. These observations
      show that brown algae polyphenols have an antiphotocarcinogenic effect which may
      be associated with the prevention of UVB-induced oxidative stress, inflammation,
      and cell proliferation in the skin.

PMID- 17019719
TI  - Prediction of peptide structure: how far are we?
AB  - Rational design of peptides is a challenge, which would benefit from a better
      knowledge of the rules of sequence-structure-function relationships. Peptide
      structures can be approached by spectroscopy and NMR techniques but data from
      these approaches too frequently diverge. Structures can also be calculated in
      silico from primary sequence information using three algorithms: Pepstr, Robetta,
      and PepLook. The most recent algorithm, PepLook introduces indexes for evaluating
      structural polymorphism and stability. For peptides with converging experimental
      data, calculated structures from PepLook and, to a lesser extent from Pepstr, are
      close to NMR models. The PepLook index for polymorphism is low and the index for
      stability points out possible binding sites. For peptides with divergent
      experimental data, calculated and NMR structures can be similar or, can be
      different. These differences are apparently due to polymorphism and to different
      conditions of structure assays and calculations. The PepLook index for
      polymorphism maps the fragments encoding disorder. This should provide new means
      for the rational design of peptides.

PMID- 17019720
TI  - Water exchange dynamics of manganese(II), cobalt(II), and nickel(II) ions in
      aqueous solution.
AB  - The first row transition metal ions Mn(2+), Co(2+), and Ni(2+) have been studied
      by classical umbrella sampling molecular dynamics simulations. The water exchange
      mechanisms, estimates of reaction rates, as well as structural changes during the
      activation process are discussed. Mn(2+) was found to react via an I(A)
      mechanism, whereas Co(2+) and Ni(2+) both proceed via I(D). Reaction rate
      constants are generally higher than those obtained by experiment but the simply
      constructed metal(II) ion-water potential reproduces the relative order quite
      well.

PMID- 17019721
TI  - Characterization of the structure and reactivity of monocopper-oxygen complexes
      supported by beta-diketiminate and anilido-imine ligands.
AB  - Copper-oxygen complexes supported by beta-diketiminate and anilido-imine ligands
      have recently been reported (Aboelella et al., J Am Chem Soc 2004, 126, 16896;
      Reynolds et al., Inorg Chem 2005, 44, 6989) as potential biomimetic models for
      dopamine beta-monooxygenase (DbetaM) and peptidylglycine alpha-hydroxylating
      monooxygenase (PHM). However, in contrast to the enzymatic systems, these
      complexes fail to exhibit C--H hydroxylation activity (Reynolds et al., Chem
      Commun 2005, 2014). Quantum chemical characterization of the 1:1 Cu-O(2) model
      adducts and related species (Cu(III)-hydroperoxide, Cu(III)-oxo, and Cu(III)
      hydroxide) indicates that the 1:1 Cu-O(2) adducts are unreactive toward
      substrates because of the weakness of the O--H bond that would be formed upon
      hydrogen-atom abstraction. This in turn is ascribed to the 1:1 adducts having
      both low reduction potentials and basicities. Cu(III)-oxo species on the other
      hand, determined to be intermediate between Cu(III)-oxo and Cu(II)-oxyl in
      character, are shown to be far more reactive toward substrates. Based on these
      results, design strategies for new DbetaM and PHM biomimetic ligands are
      proposed: new ligands should be made less electron rich so as to favor end-on
      dioxygen coordination in the 1:1 Cu-O(2) adducts. Comparison of the relative
      reactivities of the various copper-oxygen complexes as hydroxylating agents
      provides support for a Cu(II)-superoxide species as the intermediate responsible
      for substrate hydroxylation in DbetaM and PHM, and suggests that a Cu(III)-oxo
      intermediate would be competent in this process as well.

PMID- 17019722
TI  - The use of a generalized born model for the analysis of protein conformational
      transitions: a comparative study with explicit solvent simulations for chemotaxis
      Y protein (CheY).
AB  - To investigate whether implicit solvent models are appropriate for mechanistic
      studies of conformational transition in proteins, a recently developed
      generalized Born model (GBSW) was applied to a small signaling protein,
      chemotaxis protein Y (CheY), with different combinations of the phosphorylation
      state and conformation of the system; the results were compared to explicit
      solvent simulations using a stochastic boundary condition. The subtle but
      distinct conformational transitions involved in CheY activation makes the system
      ideally suited for comparing implicit and explicit solvent models because these
      conformational transitions are potentially accessible in both types of
      simulations. The structural and dynamical properties analyzed include not only
      those localized to the active site region but also throughout the protein, such
      as sidechain methyl group order parameters, backbone hydrogen bonding lifetime
      and occupancy as well as principal components of the trajectories. Overall, many
      properties were well reproduced by the GBSW simulations when compared with the
      explicit solvent calculations, although a number of observations consistently
      point to the suggestion that the current parameterization of the GBSW model tends
      to overestimate hydrogen-bonding interactions involving both charged groups and
      (charge-neutral) backbone atoms. This deficiency led to overstabilization of
      certain secondary structural motifs and more importantly, qualitatively different
      behaviors for the active site groups (Thr 87, Ala 88, the beta4-alpha4 loop) in
      response to phosphorylation, when compared with explicit solvent simulations. The
      current study highlights the value of carrying out both explicit and implicit
      solvent simulations for complementary mechanistic insights in the analysis of
      conformational transition in biomolecules.

PMID- 17019723
TI  - Comparison of implicit solvent models for the simulation of protein-surface
      interactions.
AB  - Empirical force field-based molecular simulations can provide valuable atomistic
      level insights into protein-surface interactions in aqueous solution. While the
      implicit treatment of solvation effects is desired as a means of improving
      simulation efficiency, existing implicit solvent models were primarily developed
      for the simulation of peptide or protein behavior in solution alone, and thus may
      not be appropriate for protein interactions with synthetic material surfaces. The
      objective of this research was to calculate the change in free energy as a
      function of surface-separation distance for peptide-surface interactions using
      different empirical force field-based implicit solvation models (ACE, ASP, EEF1,
      and RDIE with the CHARMM 19 force field), and to compare these results with the
      same calculations conducted using density functional theory (DFT) combined with
      the self-consistent reaction field (SCRF) implicit solvation model. These
      comparisons show that distinctly different types of behavior are predicted with
      each implicit solvation method, with ACE providing the best overall agreement
      with DFT/SCRF calculations. These results also identify areas where ACE is in
      need of improvement for this application and provide a basis for subsequent
      parameter refinement.

PMID- 17019724
TI  - Amine-containing core-shell nanoparticles as potential drug carriers for
      intracellular delivery.
AB  - The present study aimed at exploring the use of amine-containing core-shell
      nanoparticles as potential drug carriers for intracellular delivery. Stable
      nanoparticles (100-200 nm in diameter) that consisted of poly(methyl
      methacrylate) (PMMA) cores with hydrophilic poly(ethyleneimine) (PEI) shells were
      synthesized and used to study their complexation with model drug, ibuprofen (IB),
      and release it under various electrolyte concentrations. The complexed IB/PEI
      PMMA nanoparticles were characterized with FTIR, photon correlation spectroscopy,
      zeta-potential, and transmission electron microscopy (TEM). Results suggested
      that the PEI-PMMA nanoparticles could effectively complex with the IB via
      electrostatic interaction. The thick PEI shells ( approximately 30 nm)
      significantly enhanced the drug loading capacity up to 23% (w/w) of the complexed
      nanopartricle. In vitro release of the drug from the complexed nanoparticles was
      sensitive to the ionic strength of the media. Study of cellular entry of
      fluorescently labeled IB/nanoparticle complexes using a confocal laser scanning
      microscopy demonstrated that the entry of the complexed nanoparticles strongly
      depended on the complexing ratio between IB and PEI-PMMA nanoparticles.

PMID- 17019725
TI  - Dissolution kinetics of a Si-rich nanocomposite and its effect on osteoblast gene
      expression.
AB  - Silica-calcium phosphate nanocomposite (SCPC) has recently been proposed as a
      novel resorbable, bioactive, and mechanically compatible template for bone
      reconstruction. The effect of the physicochemical properties on the surface
      reactivity and dissolution kinetics of SCPC immersed in simulated body fluid
      (SBF) was investigated and compared to that of bioactive glass (BG). Moreover,
      the stimulatory effect on osteoblast gene expression of SCPC was determined using
      quantitative real-time polymerase chain reaction (qRT-PCR), and compared to that
      of hydroxyapatite (HA-200). Mercury porosimetry revealed that surface areas of
      SCPC particles containing 10 (SCPC10), 30 (SCPC30), and 50 (SCPC50) wt % Si
      content were 14-, 18-, and 32-times higher than that of BG. Inductively coupled
      plasma analysis showed that after 192 h of immersion, Si-rich SCPC50 exhibited
      controlled bulk-dissolution and released 43.1 ppm Si, which was sixfold higher
      than that released from BG (7.7 ppm). Moreover, SCPC50 showed a rapid Ca-uptake
      from SBF and developed a surface apatite layer after only 2 h, whereas a similar
      layer was detected on BG after 8 days of immersion under the same experimental
      conditions. qRT-PCR revealed that osteopontin and osteocalcin mRNA expression by
      osteoblast-like cells attached to Si-rich SCPC50 was significantly higher than
      that on HA-200 or polystyrene after 2 days in culture. This suggested a role of
      dissolved Si in stimulating the differentiation and mineralization of osteoblast
      precursor cells. The favorable physiochemical and bioactivity properties of Si
      rich SCPC nanocomposite indicate that SCPC can have wide applications as a
      synthetic bone graft for cell delivery applications in tissue engineering.

PMID- 17019726
TI  - In vitro biocompatibility of fluorcanasite glass-ceramics for bone tissue repair.
AB  - Fluorcanasite glass-ceramics were produced by controlled two stage heat-treatment
      of as-cast glasses. These glasses were modified from stoichiometric fluorcanasite
      composition by either adding P(2)O(5) or altering the molar ratios of Na(2)O and
      CaO. Commercial bioactive 45S5 Bioglass(R) was also prepared in-house to evaluate
      the relative in vitro biocompatibility of fluorcanasite glass-ceramics. The
      scanning electron microscopy (SEM) images showed that cells had colonized the
      surfaces of fluorcanasite glass-ceramics to form a confluent sheet. Quantitative
      MTT assay results were in good agreement with the qualitative SEM observations.
      It was concluded that incorporation of excess calcium oxide or P(2)O(5) in
      stoichiometric glass composition improved in vitro biocompatibility. Controlled
      heat-treatment further improved the biological response of cultured bone cells to
      modified fluorcanasite glass-ceramics when compared with their parent glasses.
      Ion release and pH data suggested a strong correlation between solubility (in
      particular, Na ion release) and biocompatibility. Reduced solubility, Na ion
      release, and related pH effects appeared to be the principal mechanisms
      responsible for improvement in in vitro biocompatibility.

PMID- 17019727
TI  - Surface modification of polymeric biomaterials: utilization of cyclodextrins for
      blood compatibility improvement.
AB  - A novel modified polymeric biomaterial surface using cyclodextrins (CDs) for
      improved blood compatibility was studied. Plasticized poly(vinyl chloride) (PVC
      P) was selected for modification and polyethylene was used as a reference
      material. The modification was achieved by polymer blending. Fibrinogen and
      albumin adsorption were utilized as indices for the assessment of the blood
      compatibility. Surface characterization confirmed that CDs were able to
      accumulate at the PVC surface and alter the surface properties. The combination
      of other hydrophilic polymers such as poly(ethylene oxide) (PEO) and
      PEO/poly(propylene oxide) (PPO) copolymers, such as Pluronic F68 (F68), with CDs
      were also investigated. These modified materials have a remarkable protein
      resistant surface. The combination of B-cyclodextrin (B-CD)/PEO and B-CD/F68 in
      certain feeding ratio are synergistic in producing enhanced blood compatibility.

PMID- 17019728
TI  - A preliminary study of oscillating electromagnetic field effects on human
      spermatozoon motility.
AB  - Some effects of extremely low frequency electromagnetic fields (ELF-EMFs) on
      human spermatozoa are reported. Significant increases in the values of the
      motility and of the other kinematic parameters have been observed when
      spermatozoa were exposed to an ELF-EMF with a square waveform of 5 mT amplitude
      and frequency of 50 Hz. By contrast, a 5 mT sine wave (50 Hz) and a 2.5 mT square
      wave (50 Hz) exposure did not produce any significant effect on sperm motility.
      The effects induced by ELF-EMF (50 Hz; 5 mT) during the first 3 h of exposure
      persisted for 21 h after the end of the treatment. These results indicate that
      ELF-EMF exposure can improve spermatozoa motility and that this effect depends on
      the field characteristics.

PMID- 17019729
TI  - Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1
      mice.
AB  - The purpose of this study using a total of 1170 B6C3F1 mice was to detect and
      evaluate possible carcinogenic effects in mice exposed to radio-frequency
      radiation (RFR) from Global System for Mobile Communication (GSM) and Digital
      Personal Communications System (DCS) handsets as emitted by handsets operating in
      the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz
      (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a
      period of 2 years to three different whole-body averaged specific absorption rate
      (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the
      organ-related tumor incidence, pairwise Fisher's test did not show any
      significant increase in the incidence of any particular tumor type in the RF
      exposed groups as compared to the sham exposed group. Interestingly, while the
      incidences of hepatocellular carcinomas were similar in EMF and sham exposed
      groups, in both studies the incidences of liver adenomas in males decreased with
      increasing dose levels; the incidences in the high dose groups were statistically
      significantly different from those in the sham exposed groups. Comparison to
      published tumor rates in untreated mice revealed that the observed tumor rates
      were within the range of historical control data. In conclusion, the present
      study produced no evidence that the exposure of male and female B6C3F1 mice to
      wireless GSM and DCS radio frequency signals at a whole body absorption rate of
      up to 4.0 W/kg resulted in any adverse health effect or had any cumulative
      influence on the incidence or severity of neoplastic and non-neoplastic
      background lesions, and thus the study did not provide any evidence of RF
      possessing a carcinogenic potential.

PMID- 17019730
TI  - EGF receptor clustering is induced by a 0.4 mT power frequency magnetic field and
      blocked by the EGF receptor tyrosine kinase inhibitor PD153035.
AB  - Atomic force microscopy (AFM), transmission electron microscopy (TEM), and
      confocal laser scanning microscopy were used to investigate the effects of a 50
      Hz 0.4 mT magnetic field (MF) on the clustering of purified epidermal growth
      factor receptors (EGFRs) and EGFRs in Chinese hamster lung (CHL) cell membrane.
      The results demonstrate that exposing purified EGFRs to the MF for 30 min induces
      receptor clustering. The peak height of apparent clusters increased from 1.42 +/-
      0.18 (sham-exposed) to 3.08 +/- 0.38 nm (exposed) while the mean half-width
      increased from 21.7 +/- 2.2 to 33.0 +/- 4.0 nm. A similar effect was also
      observed by TEM. Treatment of purified EGFR with PD153035 (PD), an EGFR-specific
      tyrosine kinase (TK) inhibitor, inhibited the MF-induced EGFR clustering of the
      purified proteins, an effect also observed for the receptors in cell membrane in
      the absence of EGF. These results strongly suggest that the 50 Hz 0.4 mT MF
      interferes with the EGFR signaling pathway, most likely by interacting with the
      cytoplasmic TK domain.

PMID- 17019732
TI  - A comparison of self-reported cellular telephone use with subscriber data:
      agreement between the two methods and implications for risk estimation.
AB  - Epidemiologic studies on adverse health effects of cellular telephone use have
      assessed exposure either by self-reported use based on questionnaire data or by
      using data on subscriptions for a cellular telephone provided by network
      operators. With the latter approach, subjects are misclassified when they
      regularly use a cellular telephone subscribed in someone else's or in a company
      name or when they subscribe for a cellular telephone which they use only
      occasionally. Self-reported use is hampered by recall difficulties and possible
      differential participation by exposure. In Denmark, we conducted a retrospective
      cohort study of cellular telephone subscribers (including the entire Danish
      population) and a case-control study on brain tumors and cellular telephone use
      (with 1355 participants) and, thus, had the opportunity to compare the two
      exposure measures with two large-scale data sets, using self-reported use as a
      "gold standard." Overall, there was a fair agreement (kappa value of 0.30, 95%
      confidence interval 0.23-0.36), with a low sensitivity (30%) and a high
      specificity (94%). Agreement was slightly better for controls, and low-grade
      glioma cases compared to high-grade glioma cases and meningioma cases. A
      comparison of odds ratios (OR) of the case-control data set based on either self
      reported use or on subscriber data shows no major differences, giving OR of 0.7
      and 0.6 for acoustic neuroma, 0.9 and 1.1 for glioma and 0.9 and 0.7 for
      meningioma. A discussion of the two exposure measures reveals that they both have
      limitations with regard to a potential underestimation of an association and
      there is some concern whether they are good enough to allow a detection of
      possibly only subtle changes in risk. These limitations can be minimized in
      prospective follow-up studies.

PMID- 17019733
TI  - Use of prenatal diagnostic procedures in pregnancies affected with birth defects,
      Hawaii, 1986-2002.
AB  - BACKGROUND: Information on the utilization of prenatal ultrasound (US),
      amniocentesis (AC), and chorionic villus sampling (CVS) in pregnancies affected
      by birth defects in the United States is limited. The intent of this study was to
      report on the utilization of these procedures in Hawaii. METHODS: Cases were all
      infants and fetuses of any pregnancy outcome with birth defects, included in a
      Hawaii birth defects registry, and delivered during 1986-2002. The rates of
      prenatal US, AC/CVS, and prenatal diagnosis were calculated. RESULTS: Prenatal US
      was performed in 76% of the cases and AC/CVS in 14% of the cases. Prenatal
      diagnosis of a birth defect was made in 16% of the cases. The prenatal US,
      AC/CVS, and prenatal diagnosis rates in 1998-2002 were 1.5, 1.5, and 1.7 times
      the rates in 1986-1991, respectively. Among all birth defects, the AC/CVS rate
      for women aged <35 years was 7% and for women aged > or =35 years was 48%. Among
      chromosomal abnormalities, the AC/CVS rate for women aged <35 years was 36% and
      for women aged > or =35 years was 66%. CONCLUSIONS: Only a fraction of the Hawaii
      birth defects cases was prenatally diagnosed. The rates for prenatal US, AC/CVS,
      and prenatal diagnosis among pregnancies affected by birth defects were higher in
      1998-2002 than in 1986-1991. AC/CVS rates were lower for maternal age <35 years.

PMID- 17019734
TI  - Acute myeloid leukemia: epidemiology and etiology.
AB  - Acute myeloid leukemias (AMLs) are infrequent, yet highly malignant neoplasms
      responsible for a large number of cancer-related deaths. The incidence has been
      near stable over the last years. It continuously shows 2 peaks in occurrence in
      early childhood and later adulthood. With an incidence of 3.7 per 100,000 persons
      and an age-dependent mortality of 2.7 to nearly 18 per 100,000 persons, there is
      a rising awareness in the Western world of AML's special attributes resulting
      from an ever-aging population. To objectively describe epidemiologic data on this
      patient population, recent publications were evaluated to make transparent the
      current trends and facts. A review of the literature is presented, reflecting
      highlights of current research with respect to AML etiology. To estimate outcome
      and discuss informed treatment decisions with AML patients of different age
      groups and different biologic risk categories, it is mandatory to consider that
      the outcome results reported in clinical trials were until now heavily biased
      toward younger patients, whereas the overall dismal prognosis documented in
      population-based studies most likely reflects the exclusion of older patients
      from aggressive treatment. The etiology for most cases of AML is unclear, but a
      growing knowledge concerning leukemogenenic agents within chemotherapy regimens
      for other malignancies is already available. This includes specific associations
      of the most frequent balanced translocations in AML, including the "good-risk"
      abnormalities comprised by the core binding factor leukemias (i.e., AML with the
      translocation (8;21) and inversion of chromosome 16, and acute promyelocytic
      leukemia with the translocation (15;17)). In contrast to these genetic
      alterations, epigenetic lesions, e.g., promoter silencing by hypermethylation of
      the p15/INK4b and other genes, are increasingly recognized as important in the
      pathogenesis of AML.

PMID- 17019735
TI  - Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive
      review of the literature with emphasis on the surgical therapy.
AB  - Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant
      tumor of vascular origin with unknown etiology and a variable natural course. The
      authors present a comprehensive review of the literature on HEH with a focus on
      clinical outcome after different therapeutic strategies. All published series on
      patients with HEH (n = 434 patients) were analyzed from the first description in
      1984 to the current literature. The reviewed parameters included demographic
      data, clinical manifestations, therapeutic modalities, and clinical outcome. The
      mean age of patients with HEH was 41.7 years, and the male-to-female ratio was
      2:3. The most common clinical manifestations were right upper quadrant pain,
      hepatomegaly, and weight loss. Most patients presented with multifocal tumor that
      involved both lobes of the liver. Lung, peritoneum, lymph nodes, and bone were
      the most common sites of extrahepatic involvement at the time of diagnosis. The
      most common management has been liver transplantation (LTx) (44.8% of patients),
      followed by no treatment (24.8% of patients), chemotherapy or radiotherapy (21%
      of patients), and liver resection (LRx) (9.4% of patients). The 1-year and 5-year
      patient survival rates were 96% and 54.5%, respectively, after LTx; 39.3% and
      4.5%, respectively, after no treatment, 73.3% and 30%, respectively, after
      chemotherapy or radiotherapy; and 100% and 75%, respectively, after LRx. LRx has
      been the treatment of choice in patients with resectable HEH. However, LTx has
      been proposed as the treatment of choice because of the hepatic multicentricity
      of HEH. In addition, LTx is an acceptable option for patients who have HEH with
      extrahepatic manifestation. Highly selected patients may be able to undergo
      living-donor LTx, preserving the donor pool. The role of different adjuvant
      therapies for patients with HEH remains to be determined.

PMID- 17019736
TI  - Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic
      predictors of survival in 1252 cases.
AB  - BACKGROUND: Medullary thyroid cancer (MTC) is a rare cancer. There is a relative
      paucity of data over the last decade with regard to the prognosis of these
      patients. Therefore, the authors used the population-based Surveillance,
      Epidemiology, and End Results (SEER) registry to update what to their knowledge
      is one of the largest series of patients with MTC reported to date. METHODS: All
      patients with a diagnosis of MTC with active follow-up in the SEER database from
      1973 to 2002 were included. Univariate and multivariate regression analyses were
      used to assess the associations between demographic, clinical, and pathologic
      characteristics of patients and survival. RESULTS: A total of 1252 patients with
      MTC were identified over 29 years of follow-up. In all, 87% of patients were
      white and 60% were female, with a mean age of 50 years. Although many variables
      were significant on univariate analysis, SEER stage and age at diagnosis were
      found to be the strongest predictors of survival in the multivariate analysis.
      Prognosis was poor in patients with advanced disease (hazards ratio [HR], 4.47),
      or those age >65 years (HR, 6.55). Patients who underwent surgery fared better
      than those who did not. Overall, 51% of patients had less than the currently
      recommended treatment guidelines for MTC. Adjuvant radiation therapy was found to
      be independently associated with a decreased survival (HR, 1.65). CONCLUSIONS:
      Stage of disease and age at diagnosis were found to be the strongest predictors
      of survival for patients with MTC. To the authors' knowledge there has been no
      change in stage at diagnosis or a significant improvement in survival noted over
      the last 30 years. Many patients underwent surgery that was deemed less than
      optimal for stage of disease.

PMID- 17019737
TI  - Gastroesophageal reflux symptoms in patients with adenocarcinoma of the esophagus
      or cardia.
AB  - BACKGROUND: The efficacy of endoscopic screening for chronic gastroesophageal
      reflux symptoms of heartburn and regurgitation in adult subjects depends on the
      sensitivity of this strategy for detecting Barrett esophagus in subjects before
      the development of adenocarcinoma of the esophagus or cardia. The aim of the
      current study was to determine what proportion of patients with cancer of the
      esophagus or cardia would have been candidates for a screening endoscopy before
      their cancer diagnosis based on the presence and duration of preceding reflux
      symptoms. METHODS: All patients with adenocarcinoma of the esophagus,
      adenocarcinoma of the cardia, or long-segment Barrett esophagus presenting for
      endoscopy at 4 tertiary care and 2 Veterans Affairs (VA) hospitals were given a
      previously validated questionnaire to determine their recall of common
      gastroesophageal reflux symptoms. RESULTS: The study population of 375 subjects
      consisted primarily of 294 (78%) white men. Only 67 of 110 patients (61%) with
      adenocarcinoma of the esophagus and 8 of 21 patients (38%) with adenocarcinoma of
      the cardia recalled symptoms of heartburn or regurgitation being present for >5
      years before their diagnosis of cancer. Only 40 of 110 patients (36%) with
      adenocarcinoma of the esophagus and 5 of 21 patients (24%) with adenocarcinoma of
      the cardia recalled weekly symptoms being present for >5 years before their
      cancer diagnosis. Of the 244 patients with Barrett esophagus, 170 (70%) recalled
      heartburn or regurgitation for >5 years and 89 patients (37%) recalled weekly
      symptoms for >5 years. CONCLUSIONS: Current practice, which uses a screening
      strategy of performing endoscopy in patients with >5 years of heartburn or
      regurgitation, can detect Barrett epithelium in only a limited proportion of
      those patients at risk for developing adenocarcinoma of the esophagus or
      adenocarcinoma of the cardia.

PMID- 17019738
TI  - Thrombocytopenia as a surrogate for cirrhosis and a marker for the identification
      of patients at high-risk for hepatocellular carcinoma.
AB  - BACKGROUND: The objective of this study was to examine the usefulness of platelet
      counts in the diagnosis of cirrhosis and for identifying high-risk individuals in
      a community-based hepatocellular carcinoma (HCC) screening program. METHODS:
      Pilot Study 1 determined the correlation between platelet counts and pathologic
      hepatic fibrosis scores among individuals with chronic hepatitis B virus (HBV)
      infection (n = 122 patients) and hepatitis C virus (HCV) infection (n = 244
      patients). Pilot Study 2 investigated proportions of individuals with
      thrombocytopenia (<150 x 10(3)/mm(3)) among patients with HCC (n = 4042
      patients). Pilot Study 3 demonstrated the correlation between platelet counts and
      ultrasonographic (US) parenchyma scores among anti-HCV-positive individuals (n =
      75 patients). The core study was a 2-stage, community-based screening for HCC
      among residents age 40 years or older in townships with a high prevalence of anti
      HCV (n = 4616 individuals) and in townships with a low prevalence of anti-HCV (n
      = 1694 individuals). Patients with thrombocytopenia were identified for US and
      alpha-fetoprotein screening. RESULTS: Among the individuals who were positive for
      anti-HCV, platelet counts decreased according to increased pathologic fibrosis
      scores or US scores for liver parenchyma disease: The best cutoff platelet count
      was 150 x 10(3)/mm(3) for a diagnosis of cirrhosis. The sensitivity and
      specificity were 68.2% and 76.4%, respectively, for pathologic cirrhosis and
      76.2% and 87.8%, respectively, for US cirrhosis. Forty-eight percent of patients
      with HCC were thrombocytopenic. The proportion of thrombocytopenia was
      significantly greater in patients with HCV-related HCC (63%) than in patients
      with HBV-related HCC (42%). In the townships with high and low anti-HCV
      prevalence, the prevalence of thrombocytopenia was 17.9% and 6.1%, respectively,
      (P < .001), respectively. Twenty-five patients were diagnosed with HCC, and all
      of those patients resided in the high-prevalence township. CONCLUSIONS:
      Thrombocytopenia was a valid surrogate of cirrhosis and a valid marker for the
      identification of individuals at high-risk for HCC, especially in areas that had
      a high prevalence of HCV.

PMID- 17019739
TI  - Focal and craniospinal irradiation for patients with intracranial germinoma and
      patterns of failure.
AB  - BACKGROUND: The authors compared the patterns of failure in patients with
      intracranial germinoma who were managed with either chemotherapy and focal
      irradiation or with craniospinal irradiation (CSI). METHODS: A retrospective
      review was conducted on 21 patients with intracranial germinoma and treated with
      radiotherapy (RT) to the central nervous system at The University of Texas M. D.
      Anderson Cancer Center from 1981 to 2002. The study group was comprised of 13
      males and 8 females with a median age at diagnosis of 19 years. Nine patients
      received chemotherapy prior to focal RT. Twelve patients received CSI. RESULTS:
      The actuarial 10-year survival rate for all patients was 86%. The overall
      survival rate at 10 years was 89% for patients who received focal RT and 83% for
      patients who received CSI (P = .73). The 10-year local control rate in the brain
      for patients who received focal irradiation was 59% compared with 100% for
      patients who received CSI (P = .08). The rate of distant control in the spine at
      5 years was 62% for patients who received focal irradiation and 100% for patients
      who received CSI (P = .04). CONCLUSIONS: Although focal techniques of irradiation
      with chemotherapy are attractive methods that limited the volume irradiated, the
      strategy appeared to be associated with increased rates of failures in the brain
      and spine.

PMID- 17019740
TI  - Phase II study of oxaliplatin in children with recurrent or refractory
      medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical
      teratoid rhabdoid tumors: a pediatric brain tumor consortium study.
AB  - BACKGROUND: An open-label Phase II study of oxaliplatin was conducted to evaluate
      its safety and efficacy in children with recurrent or refractory medulloblastoma
      (MB), supratentorial primitive neuroectodermal tumors (SPNET), and atypical
      teratoid rhabdoid tumor (ATRT). METHODS: Patients were stratified as follows:
      stratum IA, first recurrence MB with measurable disease; IB, recurrent MB with
      only cerebral spinal fluid (CSF) positivity or linear leptomeningeal disease
      (LLD); IC, MB > or =second recurrence; stratum II, recurrent SPNET; stratum III,
      recurrent ATRT. Patients received oxaliplatin, 130 mg/m(2) intravenously over 2
      hours every 3 weeks. The primary objective was to estimate the sustained response
      rate in stratum 1A. Plasma ultrafiltrate platinum pharmacokinetics were
      evaluated. RESULTS: A total of 43 patients with a median age of 8.5 years (range,
      0.6-18.9 years) were enrolled. In stratum 1A, 2 of 15 had partial responses (PRs,
      1 sustained PR). No responses were observed in other strata. The most frequent
      Grade 3 and 4 toxicities included thrombocytopenia (25.6%), neutropenia (16.3%),
      leukopenia (12%), increase in serum alanine transaminase (ALT) (7%), vomiting
      (4.7%), and sensory neuropathy (4.7%). No severe ototoxicity or nephrotoxicity
      was reported. Plasma ultrafiltrate platinum pharmacokinetic parameters were
      similar to adults, with a median clearance of 12.2 L/hr (range, 4.4-30 L/hr) and
      median area under the curve (AUC(0-infinity)) of 9.4 microg/mL/hr (range, 6.2
      13.9 microg/mL/hr). CONCLUSIONS: Oxaliplatin was well tolerated in children but
      has limited activity in children with recurrent CNS embryonal tumors previously
      treated with platinum compounds.

PMID- 17019741
TI  - Reproducibility of the measurement of submucous fibroid protrusion into the
      uterine cavity using three-dimensional saline contrast sonohysterography.
AB  - OBJECTIVE: To determine the intraobserver and interobserver reproducibility of
      measurement of the percentage of protrusion of submucous fibroids into the
      uterine cavity using three-dimensional saline contrast sonohysterography (3D
      SCSH). METHODS: Women diagnosed with submucous uterine fibroids on B-mode two
      dimensional (2D) ultrasound scan were invited to join the study and 3D-SCSH was
      carried out. 3D volume datasets were stored digitally and were examined later
      using the technique of planar reformatted sections. The reproducibilities of the
      measurement of fibroid diameter and protrusion ratio into the uterine cavity
      (ratio of the size of the segment of the fibroid protruding into the cavity to
      the total diameter of the fibroid) were examined by two independent observers who
      were unaware of the initial 2D scan findings. Interobserver reproducibility was
      assessed by calculating the difference between measurements taken by the two
      operators (limits of agreement) and interclass correlation coefficient.
      Intraobserver repeatability was assessed by calculating the difference between
      two measurements for each variable (limits of agreement) and further expressed as
      an intraclass correlation coefficient. RESULTS: Thirty-three 3D ultrasound
      volumes were examined. There was a good agreement between the observers in
      classifying the fibroids as greater or less than 50% confined to the myometrium
      (Cohen's kappa 0.81). There was no bias in measurements for both variables either
      between observers or with repeated measurements by each observer. For fibroid
      diameter and protrusion ratio the inter- and intraclass correlation coefficients
      were high (0.984-0.995), with narrow limits of agreement. CONCLUSION: 3D-SCSH is
      a reproducible method for the quantification of the percentage of a submucous
      fibroid protruding into the uterine cavity.

PMID- 17019742
TI  - Cervical length assessment in women with idiopathic polyhydramnios.
AB  - OBJECTIVE: The aims of the study were to determine cervical length among patients
      with polyhydramnios and to assess the relationship between the severity of
      polyhydramnios, cervical length and gestational age at delivery. PATIENTS AND
      METHODS: A prospective study was designed including 92 consecutive singleton
      pregnancies with polyhydramnios between 24 and 40 weeks' gestation. Cervical
      length was measured using transvaginal sonography. Polyhydramnios was defined
      when amniotic fluid index (AFI) was equal to or greater than 20 cm. A single
      sonologist performed all the examinations of the cervical length and the AFI.
      RESULTS: The median cervical length and AFI were 37.5 (range, 7-52) mm and 28.8
      (range, 20-43) cm, respectively. A significant gradual shortening of the cervical
      length was observed with advancing gestational age (P=0.027). No significant
      association was found between AFI and cervical length (P=0.24). A cut-off of 15
      mm (n=5) was associated with a significantly lower gestational age at delivery
      (30+/-2.6 weeks vs. 37.2+/-4.2 weeks, respectively, P<0.001). CONCLUSIONS: Women
      with polyhydramnios have a gradual shortening of cervical length with advancing
      gestational age. However, this finding is not related to the severity of
      polyhydramnios.

PMID- 17019743
TI  - Prenatal sonographic diagnosis of Malpuech syndrome.
AB  - Malpuech syndrome (MS) is a rare autosomal recessive syndrome featuring pre- and
      post-natal growth deficiency, mental retardation, facial dysmorphism, cleft lip
      and palate (typically midline or bilateral), caudal appendage, renal
      malformations and male genital abnormalities. A prenatal diagnosis of MS was made
      in this fetus based on the family history and a combination of conventional and
      3D prenatal ultrasound findings. The family were consanguineous with an affected
      first child. Prenatal ultrasound in the second pregnancy demonstrated bilateral
      cleft lip and palate in association with intrauterine growth retardation on
      serial prenatal ultrasound scans. Dysmorphic facial features and a small penis
      consistent with the diagnosis were confirmed on 3D scanning. Post-natal
      examination of the neonate confirmed the diagnosis of MS. To the best of our
      knowledge, this is the first prenatal diagnosis of this syndrome.

PMID- 17019744
TI  - A new cell-permeable calpain inhibitor.
AB  - The ubiquitous calpains, mu- and m-calpain, are implicated in a variety of vital
      (patho)physiological processes and therefore cell-permeable specific inhibitors
      represent important tools for defining the role of calpains in cells and animal
      models. A synthetic N-acetylated 27-mer peptide derived from exon B of the human
      calpastatin inhibitory domain 1 is known to be the most potent and selective
      reversible inhibitor of calpains. To improve the membrane permeability of this
      peptidic inhibitor, it was N-terminally extended with or disulfide-linked to the
      C-terminal 7-mer fragment of penetratin, a well-established vector for cell
      membrane translocation of bioactive compounds. Despite the shorter penetratin
      sequence, both constructs showed increased cell permeability and retained their
      full calpain inhibitory potency.

PMID- 17019745
TI  - Effects of adenovirus-expressing IL-10 in alleviating airway inflammation in
      asthma.
AB  - BACKGROUND: Allergic asthma strongly correlates with airway inflammation caused
      by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the
      immunologic regulation of cell function is yet to be acquired. Further, IL-10 has
      been found to exert both antiinflammatory and immunoregulatory activities. This
      study aimed to elucidate the therapeutic effects of IL-10 administration via
      adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)
      induced murine model of asthma. METHODS: BALB/c mice were sensitized by
      intraperitoneal injections with OVA and challenged by nebulized OVA. The
      sensitized mice were given an intratracheal delivery of adenoviral vector
      expressing the murine IL-10 gene (AdIL-10), or mock adenoviral vector 4 days
      before the inhalation challenge of the OVA. Inflammatory parameters, such as the
      development of airway hyper-responsiveness (AHR), bronchial lavage fluid
      eosinophils, and chemokines were assayed. RESULTS: Intratracheal administration
      of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly
      decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage
      fluid of OVA-sensitized and challenged mice during the effector phase.
      CONCLUSIONS: Our data showed that the intratracheal transfer of the IL-10 gene
      could affect the recruitment of inflammatory cells during the challenge phase in
      a way that would result in the inhibition of airway inflammation. These findings
      suggest that the development of an immunoregulatory strategy based on IL-10 might
      shed light on more effective treatment.

PMID- 17019746
TI  - Middle cerebral artery pulsatility index: reliability at different sampling
      sites.
AB  - OBJECTIVES: To analyze the interobserver reliability of measurement of the middle
      cerebral artery (MCA) pulsatility index (PI) at two different sampling sites.
      METHODS: This study included 100 consecutive singleton pregnancies between 24 and
      40 weeks with normal fetal growth. The PI was calculated by two independent
      operators at proximal and distal sampling sites of the near-field MCA.
      Reliability analyses were performed between observers at each sampling site by
      means of the intraclass correlation coefficient (ICC) for agreement. Differences
      between observers were explored and agreement limits calculated by means of the
      Bland-Altman test. RESULTS: Satisfactory flow velocity waveforms were obtained
      successfully in each fetus at both sampling sites. Peak systolic, end-diastolic
      and time-averaged maximum velocities were significantly higher at the proximal
      compared with the distal sampling site. Conversely, PI was significantly higher
      at the distal compared with the proximal site. ICCs for PI were 0.3 and 0.33 at
      the proximal and the distal sampling sites, respectively. The 95% interval of the
      PI differences between observers were +0.91 and -1.14 at the proximal and +1.03
      and -1.08 at the distal sampling sites. In about 30% of the cases the PI
      difference between observers was greater than 0.5 at both sampling sites.
      CONCLUSIONS: Moderate interobserver reliability in the measurement of end
      diastolic and time-averaged maximum MCA flow velocities results in limited
      agreement of the PI calculation at both proximal and distal sampling sites. These
      results may preclude its clinical applicability.

PMID- 17019747
TI  - Diagnosis of paraovarian cysts using transvaginal sonography combined with CA 125
      determination.

PMID- 17019748
TI  - South African Health Minister must go, say scientists.

PMID- 17019749
TI  - Spotlight: Alberto   Zanchetti, MD, FESC.

PMID- 17019750
TI  - Why treat anemia in the preoperative period of joint replacement surgery with
      erythropoietin? IMPACT consults. Proceedings of the 2nd Annual Cleveland Clinic
      Perioperative Medicine Summit.
AB  - Treatment of anemia in the perioperative period of major orthopedic surgery
      decreases the need for blood transfusion and improves perioperative outcomes. Use
      of epoetin alfa in this setting is FDA-approved and provides significant benefit
      to qualified and carefully chosen patients.

PMID- 17019751
TI  - One year later: remembering Katrina caregivers.

PMID- 17019752
TI  - A young nurse's sensitivity soothes a patient.

PMID- 17019753
TI  - Readers speak out on the nursing "shortage".

PMID- 17019755
TI  - Readers speak out on the nursing "shortage".

PMID- 17019756
TI  - What can anticonvulsants do for chronic pain?

PMID- 17019757
TI  - Can you rapidly distinguish these endocrine emergencies?

PMID- 17019758
TI  - Comments on Point:Counterpoint series "Lactic acid accumulation is an
      advantage/disadvantage during muscle activity".

PMID- 17019759
TI  - The burden of upper gastrointestinal endoscopy in patients with Barrett's
      esophagus.
AB  - BACKGROUND AND STUDY AIMS: Patients with Barrett's esophagus are recommended to
      undergo regular surveillance with upper gastrointestinal endoscopy, an invasive
      procedure that may cause anxiety, pain, and discomfort. We assessed to what
      extent patients perceived this procedure as burdensome. PATIENTS AND METHODS: A
      total of 192 patients with Barrett's esophagus were asked to fill out
      questionnaires at 1 week and immediately before endoscopy, and at 1 week and 1
      month afterwards. Four variables were assessed: (i) pain and discomfort
      experienced during endoscopy; (ii) symptoms; (iii) psychological burden, i. e.,
      anxiety, depression and distress levels (Hospital Anxiety and Depression scale,
      Impact of Event Scale); and (iv) perceived risk of developing adenocarcinoma.
      RESULTS: At least one questionnaire was returned by 180 patients (94 %), 151
      completed all four (79 %). Of all patients, only 14 % experienced the endoscopy
      as painful. However, 59 % reported it to be burdensome. Apart from an increase in
      throat ache (47 % after endoscopy versus 12 % before), the procedure did not
      cause physical symptoms. Patients' anxiety, depression, and distress levels were
      significantly increased in the week before endoscopy compared with the week
      after. Patients perceiving their risk of developing adenocarcinoma as high
      reported higher levels of psychological distress and that the procedure was a
      greater burden. CONCLUSIONS: Upper gastrointestinal endoscopy is burdensome for
      many patients with Barrett's esophagus and causes moderate distress. Perception
      of a high risk of adenocarcinoma may increase distress and the burden experienced
      from the procedure. The benefits of endoscopic surveillance for patients with
      Barrett's esophagus should be weighed against its drawbacks, including the short
      term burden for patients.

PMID- 17019760
TI  - Vascular ectasia of the whole intestine as a cause of recurrent gastrointestinal
      bleeding after high-dose chemotherapy.
AB  - We present the first case in the literature of vascular ectasia of the whole
      intestine as a cause of recurrent and profuse gastrointestinal bleeding in a
      patient with relapsing Hodgkin's disease. The 17-year-old patient experienced
      early relapse of his Hodgkin's disease after first-line chemotherapy. Salvage
      chemotherapy was followed by high-dose chemotherapy and autologous stem cell
      transplantation. Complete remission was achieved after another relapse by means
      of a second transplant. The patient presented with profuse gastrointestinal
      bleeding 5 months later, however. Gastric antral vascular ectasia following
      hematopoietic stem cell transplantation was diagnosed by endoscopy, with
      histological confirmation. Similar lesions were found in the duodenum, the ileum,
      and throughout the entire colon. In conclusion, vascular ectasia of the whole
      intestine should be considered as cause of acute gastrointestinal bleeding after
      stem cell transplantation. Physicians should be aware of this complication
      because its onset is typically delayed. Importantly, this disease is not limited
      to patients who have undergone allogeneic transplantation, but can also occur
      after autologous transplantation.

PMID- 17019761
TI  - Colonic explosion during endoscopic polypectomy: avoidable complication or bad
      luck?
AB  - We were confronted recently by an intraluminal colonic explosion during a colonic
      polypectomy procedure using snare loop electrocautery, probably caused by the
      presence of hydrogen and/or methane in combustible concentrations. Our patient
      needed immediate surgery, when several lacerations were found in the colon: a
      right hemicolectomy and a partial sigmoid resection with primary anastomoses were
      performed. Colonic bacteria, rests of fecal fluids, certain cleansing solutions,
      and oxygen insufflation are the main factors involved in cases of colonic
      explosion. We describe this dramatic event in our patient and discuss whether
      this complication might be avoidable in the future.

PMID- 17019762
TI  - Effective use of preassessment appointments.

PMID- 17019763
TI  - Capitated hip implant pricing is back.

PMID- 17019764
TI  - Mosquito production from four constructed treatment wetlands in peninsular
      Florida.
AB  - Several techniques were used to sample adult and immature mosquitoes in 4
      constructed treatment wetlands in Florida. Adults of 19 species (7 genera) of
      mosquitoes were collected, and immatures of the most abundant species and of 60%
      of all species also were collected. Few significant differences between sites and
      stations in the numbers of mosquitoes collected were discovered. Culex
      nigripalpus Theobald was the most abundant mosquito found in adult (carbon
      dioxide-baited suction traps) and ovitrap collections, whereas Mansonia spp. and
      Uranotaenia spp. were most common in pump-dip-grab samples. The roles of rooted
      and floating vegetation and of water quality in determining mosquito production
      from these areas are discussed.

PMID- 17019765
TI  - Seasonal abundance of Culex restuans and Culex pipiens in southwestern Virginia
      through ovitrapping.
AB  - Ovitrap collections were done to determine the seasonal distribution and
      ovipositional activity of Culex restuans and Culex pipiens in southwestern
      Virginia during summers 2002 and 2003. In both years, Cx. restuans was the first
      species collected and was the dominant species throughout the collecting period.
      More than 90% of the collections were comprised of Cx. restuans. Two oviposition
      peaks occurred in both years for Cx. restuans, the first in June and second in
      the middle of July. Culex pipiens made up less than 7% of the total catch and
      started to occur in the traps in the middle of the trapping season with a peak
      occurring in August. Although ovipositional activity began to decline for Cx.
      restuans, at the end of the trapping period, there was a slight increase in
      ovipositional activity for Cx. pipiens, but not enough to result in a crossover.
      A third species, Culex salinarius, was collected in the traps, but the total
      number of egg rafts accounted for less than 1% of the total collection.

PMID- 17019766
TI  - The anopheline fauna of Papua New Guinea.
AB  - Surveys for anopheline mosquitoes were conducted throughout the mainland of Papua
      New Guinea from 1992 to 1998 with the aim of mapping the distribution of the
      anopheline fauna. Larval collections, adult trap, and human landing collections
      indicated the presence of seven species (other than those belonging to the
      Anopheles punctulatus group); these were An. bancroftii, An. annulipes, An,
      karwari, An. longirostris, An. meraukensis, An. novaguinensis, and An. subpictus.
      The distribution and ecology of these species is discussed.

PMID- 17019767
TI  - Different spatial distribution of Aedes aegypti and Aedes albopictus along an
      urban-rural gradient and the relating environmental factors examined in three
      villages in northern Thailand.
AB  - A larval survey of dengue vectors was conducted from July to November 1966 and
      from May to November 1997 in Chiangmai Province, Thailand. Three villages in
      urban, transition, and rural areas were selected for the survey to clarify the
      spatial distribution of Ae. aegypti and Ae. albopictus along an urban-rural
      ecological gradient. The average number of Ae. aegypti larvae in larvitraps was
      higher in the urban area than in the rural area, as we expected, whereas the
      opposite was found for Ae. albopictus, rural area > urban area. A house survey of
      larvae-inhabiting containers showed significant differences in the number and
      composition of these containers among the study areas. Significant differences
      were also found in the average distance between houses, average tree height, and
      average percentage of vegetation cover for each house. The seasonal pattern of
      rainfall recorded in each study area did not show great differences among the
      study areas. The response of Ae. aegypti and Ae. albopictus to the urban-rural
      gradient is discussed in relation to the possibility of applying geographic
      information system techniques to plan the control strategy and surveillance of
      dengue vectors.

PMID- 17019768
TI  - New tools for surveillance of adult yellow fever mosquitoes: comparison of trap
      catches with human landing rates in an urban environment.
AB  - A novel mosquito trapping system, the BG-Sentinel trap, was evaluated as a
      monitoring tool for adult Aedes aegypti in field tests in the city of Belo
      Horizonte, Brazil. Human landing/biting collections, a gas-powered CO2 trap, and
      a Fay-Prince trap with only visual cues serving as references to evaluate the
      efficacy of the new trap. The BG-Sentinel is a simple suction trap that uses
      upward-directed air currents as well as visual cues to attract mosquitoes. The
      trap was tested with a new dispenser system (BG-Lure) that releases artificial
      human skin odors and needs no CO2. In comparison with the two other traps, the BG
      Sentinel caught significantly more Ae. aegypti. Although human landing rates were
      the highest, there was no significant difference between human landing rates and
      the capture rates of the BG-Sentinel trap. The finding indicates that the trap
      can be considered as an acceptable alternative to human landing/biting
      collections in the surveillance of adult host-seeking dengue vectors. The
      addition of BG-Lure to the gas-powered CO2 trap greatly increased its efficacy.
      This combination, however, was not significantly more effective than the BG
      Sentinel without CO2. In a 6-month comparison between the BG-Sentinel and a
      sticky ovitrap for gravid females, the BG-Sentinel proved to be a far more
      efficient and sensitive tool to measure the density of Ae. aegypti populations.

PMID- 17019769
TI  - Study of flying height of culicid species in the northern part of the Republic of
      Korea.
AB  - The vertical distribution of mosquitoes (Diptera, Culicidae) was evaluated in
      Paju County in northern South Korea by using Centers for Disease Control and
      Prevention (CDC) miniature light traps with ultraviolet light and dry ice (CO2)
      as attractants. CDC traps were placed at 1, 3 and 5 m above the ground near rice
      paddies in a relatively open agricultural ara. Traps wer hung on two scaffold
      towers (6 m height) spaced approximately 300 m aprt. Each trap operated 9 nights
      from August 3 to 16, 2002, and collected 9,971 mosquitoes: Aedes Vexans nipponii,
      145.2; Culex tritaeniorhynchus, 34.9; Anopheles sinensis, 21.3; and Culex
      pipiens, 17.3 female mosquitoes/trap/night. Average flight height was calculated
      from the total number of catches in both stations. Overall, Cx. pipiens (2.52 +/-
      0.35 m) was found to be the highest flying species followed by An. sinensis (2.04
      +/- 0.79 m), Ae. vexans nipponii (1.96 +/- 0.44 m), and Cx. tritaeniorhynchus
      (1.76 +/- 0.68 m), respectively. Although no significant difference in flying
      height among species was encountered, every species showed their own flight
      preference range, matching with their host preference.

PMID- 17019771
TI  - Demographic and spatial analysis of West Nile virus and St. Louis encephalitis in
      Houston, Texas.
AB  - This descriptive prevalence study describes the relationships between mosquito
      density and the presence of arboviruses (in mosquitoes and humans) with various
      socioeconomic and environmental factors present near the time of teh arbovirus
      outbreak in Harris County, Texas, in 2002. This study suggests that mosquito
      density increased if the trap was located in an area with a large number of
      containers that may inadvertently retain rainwater (P = 0.056). When considering
      only virus-positive mosquitoes, significant relationships were observed if the
      trap was located near waste materials (P < 0.001) or near containers that may
      inadvertently retain rainwater (P = 0.037). Furthermore, the presence of
      arbovirus activity (in mosquitoes or humans) in a geographic area tended to be
      associated with the socioeconomic status of the local community. Although the
      results of socioeconomic comparisons were not significant, they were suggestive,
      demonstrating an interesting trend. Compared with communities where virus
      activity was not observed, the socioeconomic status of the arbovirus-positive
      community was consistently lower. Specifically, results showed that the
      populations residing in virus-positive census tracts attained less education,
      earned less income per household, and were more likely to be below the poverty
      level. In addition, this study found that virus-positive mosquitoes were randomly
      distributed throughout the study area, whereas severe human infection cases were
      clustered. Based on the results of this study, we conclude that the health
      outcome of a local community as it relates to West Nile virus and St. Louis
      encephalitis is dependent on many factors, including eh socioeconomic and
      environmental characteristics of the community.

PMID- 17019770
TI  - Comparison of mosquito trapping method efficacy for West Nile virus surveillance
      in New Mexico.
AB  - As part of the West Nile virus surveillance program for the state of New Mexico,
      13 sites along the Rio Grande River were sampled for mosquitoes during spring and
      summer 2003. We evaluated 3 different trapping procedures for their effectiveness
      at capturing selected species of mosquitoes. The 3 methods used were a dry ice
      baited Centers for Disease Control and Prevention (CDC) light trap set 1.5 m
      above the ground (standard method), a CDC light trap suspended within the forest
      canopy, and a gravid trap set on the ground. Thirteen sites were sampled for 10 1
      night periods biweekly from May through September. The relative numbers of
      captured Culex tarsalis, Cx. salinarius, Cx. quinquefasciatus, and Aedes vexans
      as well as the numbers of total recorded captures of all species were compared
      for each trapping method. Significant differences were observed for each species
      by location and by trapping method. Culex tarsalis was most commonly caught in
      canopy or standard CDC traps, especially in cottonwood bosque. Culex salinarius
      was found most frequently in association with marshy water, and was most often
      caught in gravid or standard light traps. Culex quinquefasciatus was captured
      almost exclusively in gravid traps within urban areas. Aedes vexans was primarily
      sampled in standard CDC light traps and found most frequently in wooded areas
      near floodplains. With the exception of Cx. Quinquefasciatus, no species was
      collected significantly more frequently in gravid or canopy traps than in the
      standard CDC light trap. Our findings do not support altering the methods
      currently used in New Mexico, namely, the use of 1.5-m CDC light traps and gravid
      traps. An increased use of gravid traps seems to be warranted in monitoring urban
      vector populations (specifically Cx. quinquefasciatus and Cx. salinarius) that
      may be involved in human transmission.

PMID- 17019772
TI  - West Nile virus surveillance in mosquitoes in New York State, 2000-2004.
AB  - A West Nile virus (WNV) surveillance system was created and implemented in New
      York State (NYS) in 2000 and described previously (White et al. 2001). We examine
      and evaluate the results of mosquito and virus surveillance for 2000 through 2004
      exclusive of New York City. Forty-nine counties submitted 1,095,426 mosquitoes in
      35,280 pools for WNV assay. Specimens of 47 species were tested, with Culex
      species accounting for 47.6% of all pools tested. WNV was detected in 814 pools
      from 10 species, with combined Culex pipiens/Culex restuans pools accounting for
      90.8% of all detections. Pools submitted from gravid traps were 5.7 times more
      likely to be positive than submissions from carbon dioxide-baited light traps.
      Most human WNV cases resided in counties that conducted mosquito surveillance.
      Local health departments' use of mosquito surveillance information often led to
      an enhanced disease prevention response. In NYS, Cx. pipiens/Cx. restuans groups
      are most likely vectors of WNV. Future efforts to improve system efficacy are
      discussed.

PMID- 17019773
TI  - Effects of time after infection, mosquito genotype, and infectious viral dose on
      the dynamics of Culex tarsalis vector competence for western equine
      encephalomyelitis virus.
AB  - The vector competence of Culex tarsalis Coquillett for the BFS 1703 strain of
      western equine encephalomyelitis virus (WEEV) changed significantly as a function
      of time after infection, mosquito genotype, and infectious virus dose. After
      ingesting a high virus dose (5 log10 plaque-forming units [PFU]/0.1 ml), female
      of the susceptible high virus producer (HVP) strain rapidly amplified the virus,
      developed a disseminated infection, and efficiently transmitted WEEV by 4 days
      postinfection (dpi). The quantity of virus expectorated peaked at 4 dpi (mean 3.4
      log10 PFU), and the percentage of females transmitting per os peaked at 7 dpi
      (80%); both measures of transmission subsequently decreased to low levels
      throughout the remainder of infected life. HVP females imbibing a low virus dose
      (3 log10 PFU/0.1 ml) were infected less frequently and took longer to amplify
      virus to levels recorded for the high virus dose group and did not transmit virus
      efficiently, thereby indicating midgut infection and escape barriers were dose
      and time dependent. These data emphasized the importance of elevated avian
      viremias in Cx. tarsalis vector competence. Females from the WEEV-resistant (WR)
      strain and two wild-type strains from Kern and Riverside counties were
      significantly less susceptible to infection at both high and low doses than was
      the HVP strain. Overall, females with a high virus titer more frequently had a
      disseminated infection, but there did not seem to be a distinct threshold
      demarcating this relationship. In marked contrast, all infected females
      transmitting virus had body titers >4.3 log10 PFU, and most had titers >4.8 log10
      PFU. These data indicated that not all females with a disseminated infection
      transmitted virus because of the presence of one or more salivary gland barriers.

PMID- 17019774
TI  - Stormwater ponds, constructed wetlands, and other best management practices as
      potential breeding sites for West Nile virus vectors in Delaware during 2004.
AB  - We performed longitudinal surveys of mosquito larval abundance (mean mosquito
      larvae per dip) in 87 stormwater ponds and constructed wetland in Delaware from
      June to September 2004. We analyzed selected water quality factors, water depth,
      types of vegetation, degree of shade, and level of insect predation in relation
      to mosquito abundance. The 2004 season was atypical, with most ponds remaining
      wet for the entire summer. In terms of West Nile virus (WNV) vectors, wetlands
      predominantly produce Aedes vexans, culex pipiens pipiens, and Culex restuans.
      Retention ponds generally produced the same species as wetlands, except that Cx.
      p. pipiens was more abundant than Cx. restuans in retention ponds. Aedes vexans
      and Culex salinarius were the most abundant species to Conservation Restoration
      Enhancement Program ponds. Sand filters uniquely produced high numbers of Cx.
      restuans, Cx. p. pipiens, and Aedes japonicus japonicus, a newly invasive vector
      species. Site that alternately dried and flooded, mostly detention ponds,
      forebays of retention ponds, and some wetlands often produced Ae. vexans, an
      occasional WNV bridge vector species. Overall, seasonal distribution of vectors
      was bimodal, with peaks occurring during early and late summer. Ponds with
      shallow sides and heavy shade generally produced an abundance of mosquitoes,
      unless insect predators were abundant. Bright, sunny ponds with steep sides and
      little vegetation generally produced the fewest mosquitoes. The associations
      among mosquito species and selected vegetation types are discussed.

PMID- 17019775
TI  - Mosquito larvicidal activity of aromatic medicinal plant oils against Aedes
      aegypti and Culex pipiens pallens.
AB  - Larvicidal activity of essential oils derived from 11 aromatic medicinal plants
      against early 4th-stage larvae of Aedes aegypti and Culex pipiens pallens was
      tested in the laboratory. At 100 ppm, the essential oils of all plants caused
      100% mortality against Ae. aegypti and Cx. pipiens pallens. At 25 ppm, the
      essential oils of Citrus bergamia, Cuminum myrrha, and Pimenta racemosa caused
      100% mortality against larvae of Ae. aegypti and Cx. pipiens pallens. The oil of
      C. begamia caused 32.5% and 24.5% mortality against Ae. aegypti and Cx. pipiens
      pallens at 12.5 ppm, but 24.2% and 0% mortality against Ae. aegypti and Cx.
      pipiens pallens at 6.25 ppm, respectively. The oil of P. racemosa caused 52.3%
      and 38.5% mortality against Ae. aegypti and Cx. pipiens pallens at 12.5 ppm, but
      32.2% and 0% mortality against Ae. aegypti and Cx. pipiens pallens at 6.25 ppm,
      respectively. The larvicidal activity of oils of C. bergamia, C. myrrha, and P.
      racemosa was significantly reduced when used at 6.25 ppm. These plants warrant
      further studies as possible agents for mosquito control.

PMID- 17019776
TI  - Field efficacy of the BG-Sentinel compared with CDC Backpack Aspirators and CO2
      baited EVS traps for collection of adult Aedes aegypti in Cairns, Queensland,
      Australia.
AB  - In this study, we compared the efficacy of the newly available BG-Sentinel with
      an established "gold standard,", the CDC Backpack Aspirator, and a CO2-baited EVS
      trap for the collection of Aedes aegypti (L.) in Cairns, Australia. BG-Sentinels
      collected significantly more (P = 0.017) female Ae. aegypti (mean per collection,
      1.92 +/- 0.39) than both the CDC Backpack Aspirator (1.00 +/- 0.35) and the EVS
      trap (0.71 +/- 0.27). Male-only and combined male-female Ae. aegypti collections
      for th BG-Sentinel and the CDC Backpack Aspirator were also greater than EVS trap
      collections. The CDC Backpack Aspirator and the BG-Sentinel captured
      proportionally fewer females compared with the EVS trap. The BG-Sentinel was the
      most Ae. aegypti specific collection method. The CDC Backpack Aspirator collected
      proportionally more bloodfed Ae. aegypti than the other methods, which collected
      a greater proportion of nullipars. The data presented here will aid researchers
      in deciding what Ae. aegypti sampling device best suits their needs. BG-Sentinels
      and CDC Backpack Aspirators should be considered as alternatives to human-bait
      collections for Ae. aegypti sampling.

PMID- 17019777
TI  - Space treatments of insecticide for control of dengue virus vector Aedes aegypti
      in southern Mexico. I. Baseline penetration trials in open field and houses.
AB  - We studied the efficacy of space ultra-low volume treatments of 3 insecticides
      for the control of the dengue virus vector Aedes aegypti in southern Mexico.
      Insecticides tested were permethrin (Aqua-Reslin Super), d-phenothrin (Anvil),
      and cyfluthrin (Solfac), applied at rates of 10.87, 7.68, and 2 g/ha,
      respectively, by using London Fog, HP910-PHXL, or Micro-Gen pumps mounted on
      vehicles. Studies included 1) open field penetration tests and 2) house
      penetration tests. Open field tests indicated that Anvil and Solfac were more
      effective than Aqua-Reslin Super. In house tests, Anvil yielded the highest
      mosquito mortalities (>/=88%) of the three insecticides in the front porch,
      living room, bedroom, and backyard. Therefore, Anvil proved to be better than
      other insecticides evaluated to control Ae. aegypti in Chiapas, Mexico.

PMID- 17019778
TI  - Field evaluation of deet, Repel Care, and three plant based essential oil
      repellents against mosquitoes, black flies (Diptera: Simuliidae) and land leeches
      (Arhynchobdellida: Haemadipsidae) in Thailand.
AB  - Diethyl methyl benzamide, or deet, a commercial plant-based repellent (Repel
      Care), and essential ils from 3 species of plants (finger root rhizomes, guava
      leaves, and turmeric rhizomes), steam distillated and formulated as insect
      repellents, were evaluated in the field on human volunteers against hematophagous
      mosquitoes, black flies, and land leeches in Thailand. Field trials were
      conducted against wild mosquitoes in Bang Bua Thong District, Nonthaburi
      Province, and in the Thap Lan National Park Headquarters, Nadee District,
      Pranchinburi Province; anthroophilic black flies (Diptera: Simuliidae) at the
      Forestry Fire Control Station in Doi Inthanon National Park, Chomthong district,
      Chiang Mai Province; and land leeches (Arhynchobdellida: Haemadipsidae) in the
      Khao Yai National Park, Pak Chong District, Nakhon Ratchasima Province. The 3
      experimental plant-based essential oil formulations as well as Repel Care and
      deet provided complete protection from mosquito landing and biting for up to 9 h
      (duration of the experiment). Similar results were obtained with the 5 products
      against black flies, providing 100% protection for 9 h but 96-82% protection
      after 10 and 11 h posttreatment. The 5 repellent products also provided 100%
      protection against land leeches for at least 8 h. Thi is the 1st report of
      repellency of plant-based repellents against black flies and land leeches in
      Thailand. The identification and availability of inexpensive sources of plant
      based oils, i.e., finger root rhizomes, guava leaves, and turmeric rhizomes
      providing long-lasting repellency against blood-sucking organisms are promising
      leads into commercial production of relatively safe and effective repellents.

PMID- 17019780
TI  - Diagnostic tests for HIV resistance are created as quickly as the new drugs.
      Research is leading individualized medicine evolution.

PMID- 17019779
TI  - Larvicidal activity of some Cerrado plant extracts against Aedes aegypti.
AB  - One hundred ninety hexanic and ethanolic extract from 27 plant species from the
      Cerrado biome of Brazil were tested for larvicidal activity against 3rd-stage
      Aedes aegypti larvae at 500 microg/ml. Fourteen extracts from 7 species showed
      activity (>65% mortality) against the larvae. Of these Dugeutia furfuracea,
      Piptocarpha rotundifolia, Casearia sylvestris var. lingua, Serjania lethalis, and
      Xylopia aromatica were active at 56.6, 162.31, 232.4, 285.76, and 384.37
      microg/ml, respectively. Annona crassiflora and Cybistax antisyphilitica showed
      activity at 23.06 and 27.61 microg/ml. The larvicidal properties of these species
      are described for the first time, and may prove to be promising in active
      chemical compound isolation.

PMID- 17019781
TI  - CDC's latest STD guidelines have changes for HIV clinicians to follow. Routine
      screening for STDs, HIV recommended.

PMID- 17019782
TI  - Latest STD treatment guidelines recommend these screening questions. Use
      normalizing language with patients.

PMID- 17019783
TI  - Problematic HIV patients benefit from comprehensive team approach to care.
      Glucose intolerance higher in HIV patients.

PMID- 17019784
TI  - Adherence strategies. Study finds benefits to providing case management to
      homeless HIV patients. ART adherence and CD4 cell counts were improved.

PMID- 17019785
TI  - FDA notifications. HIV/AIDS patients should avoid raw oysters from Pacific NW.

PMID- 17019786
TI  - MK-0518 and GS-9137: two promising integrase inhibitors in the pipeline.
AB  - Possibly the most exciting news to come out of the 13th Conference on
      Retroviruses and Opportunistic Infections, held in Denver last February,
      concerned clinical trials of two experimental drugs in a new class: integrase
      inhibitors. If successful in further trials, integrase inhibitors could
      revitalize the treatment regimens of people living with multidrug-resistant HIV.

PMID- 17019787
TI  - Switching antiretroviral therapy.

PMID- 17019788
TI  - Structured treatment interruptions: after SMART.
AB  - The recent termination of several major studies of structured treatment
      interruption (STI)--the term for taking a planned break from anti-HIV medications
      -has drawn heightened attention to this treatment strategy. Always a
      controversial and intriguing approach, STI has been the focus of large-scale
      trials only in the last several years. Since January, three such studies have
      been halted early after researchers found that individuals who stop and start
      highly active antiretroviral therapy (HAART) are at greater risk of HIV disease
      progression and serious illness than those who take treatment continuously.
      However, other studies show that many questions remain about the risks involved.
      There is still considerable interest in both the research and HIV positive
      communities in better understanding the effects of interrupting anti-HIV therapy.
      This article provides an overview of STI, including some of the recent research
      findings, and examines several issues that people contemplating a break from
      treatment should consider.

PMID- 17019789
TI  - Women and HIV. Microbicides for HIV prevention.
AB  - We all know about the "feminization" of AIDS. Approximately 8000 women and girls
      are infected with HIV daily, the vast majority by their husbands or boyfriends.
      In Africa, women make up 60% of all people living with HIV/AIDS, and girls make
      up 6% of HIV positive African youth. While fewer than half of all new HIV
      infections in the United States occur among women, the transmission pattern is
      similar. Heterosexual contact is the source of at least 78% of all new infections
      among U.S. women. Biologically, a woman is at least twice as likely as a man to
      contract HIV from a single act of unprotected vaginal intercourse. Even with the
      "female condom," a woman cannot protect herself during heterosexual sex without
      the cooperation of her partner. The "ABCs" (abstain, be faithful, use condoms)
      fail millions of women who lack the social and economic power to negotiate when
      and how sex occurs and whether protection is used. Microbicides could change this
      picture with just a simple cream, foam, or gel that can be inserted vaginally to
      protect women condom use isn't possible. Five candidate microbicides are now in
      large-scale efficacy trials and dozens more are in the preclinical and clinical
      trial pipeline. Research to develop rectal microbicides is also finally underway.
      We now have the scientific means and the public health motivation to put the
      first totally new HIV prevention technology into the hands of receptive sex
      partners--male and female--in the very near future.

PMID- 17019790
TI  - Methamphetamine and HIV.
AB  - When the New York City Department of Health and Mental Hygiene announced in
      January 2005 that a gay man in his forties had become infected with a multidrug
      resistant "superstrain" of HIV and had progressed to AIDS within a few months,
      much was made of the man's use of methamphetamine. The case highlighted two
      important aspects of the intersection of methamphetamine use and HIV. First is
      the fairly well-established role the drug can play in facilitating new infections
      by lowering users' inhibitions and encouraging sexual practices that increase the
      risk of HIV transmission. The second aspect is the idea that methamphetamine
      somehow speeds up the HIV disease process. There is little evidence of a direct
      interaction between meth and HIV that accelerates immune decline, but meth use
      can undermine the general health of the user. There is also a growing body of
      evidence that meth's harmful effects on the brain may be exacerbated in people
      with HIV, and that many HIV-related neurological impairments may be worsened by
      meth use.

PMID- 17019791
TI  - Screening for the metabolic syndrome.

PMID- 17019792
TI  - Topical selamectin was 100% ineffective in eliminating Syphacia infections in
      rats and mice.

PMID- 17019793
TI  - Whiplash can have lesions.

PMID- 17019794
TI  - Biomarkers in Diagnosis of pancreatic carcinoma in fine-needle aspirates.
AB  - This study was undertaken to determine whether recently identified proteins could
      be translated to clinical practice as markers to distinguish pancreatic
      adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples.
      Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were
      stained for clusterin-beta, MUC4, survivin, and mesothelin. For each biomarker,
      the staining patterns in adenocarcinoma and in reactive ductal epithelium were
      evaluated and compared. Clusterin-beta stained reactive ductal epithelium
      significantly more frequently than pancreatic adenocarcinoma (P < .001). In
      comparison, MUC4 and mesothelin were expressed more frequently in pancreatic
      adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P <
      .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin
      beta (90% vs 7%; P < .001) were noted significantly more frequently in
      adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-beta and
      MUC4 can help distinguish reactive ductal epithelial cells from the cells of
      pancreatic adenocarcinoma in FNA samples.

PMID- 17019795
TI  - A needs assessment of chronic pain in psychiatric practice.

PMID- 17019796
TI  - Expression of protein tyrosine kinases in head and neck squamous cell carcinomas.

PMID- 17019797
TI  - Tracking health care costs: spending growth remains stable at high rate in 2005.
AB  - This Data Bulletin is based on data from the Milliman Health Cost Index 2005
      Series ($0 deductible), which is designed to reflect claims trends faced by
      private insurers; the U.S. Bureau of Labor Statistics' (BLS) Producer Price Index
      for general medical and surgical for general medical and surgical hospitals and
      for physicians' offices to track hospital and physician prices; the BLS's
      Consumer Price Index for prescription drugs and medical supplies to track
      prescription drug prices; and the Kaiser Family Foundation/Health Research and
      Educational Trust 2006 Survey of Employer Health Benefits. It is adapted from
      "Tracking Health Care Costs: Continued Stability But At High Rates In 2005," by
      Paul B. Ginsburg, Bradley C. Strunk and Michelle I. Banker of HSC; and John P.
      Cookson of Milliman, Health Affairs, Web-exclusive publication, Oct. 3, 2006,
      www.healthaffairs.org.

PMID- 17019798
TI  - [Comments on the article Issues of congenital syphilis in the past twenty years-
      I. Etiology, epidemiology and diagnosis].

PMID- 17019799
TI  - [Contribution to guidelines for care of MRSA-positive patients].

PMID- 17019800
TI  - [What is the meaning of polemics?].

PMID- 17019801
TI  - [Ectoparasites and other types in the political biotope].

PMID- 17019802
TI  - Celiac disease--hidden and dangerous.

PMID- 17019803
TI  - Control of cardiac hypertrophy and heart failure by histone
      acetylation/deacetylation.
AB  - The adult heart responds to acute and chronic stresses by a remodelling process
      that is accompanied by myocyte hypertrophy, impaired contractility, and pump
      failure, often culminating in sudden death. Pathological growth and remodelling
      of the adult heart is often associated with the reactivation of a fetal cardiac
      gene program that further weakens cardiac performance. Recent studies have
      revealed key roles for histone deacetylases (HDACs) in the control of
      pathological cardiac growth. Class II HDACs associate with the MEF2 transcription
      factor, and other factors, to maintain normal cardiac size and function. Stress
      signals lead to the phosphorylation of class II HDACs and their export from the
      nucleus to the cytoplasm, with consequent activation of genes involved in cardiac
      growth. HDAC knockout mice are hypersensitive to stress signalling and develop
      massively enlarged hearts in response to various pathological stress stimuli due
      to an inability to counteract pathological signalling to MEF2. Strategies for
      normalizing gene expression in the failing heart by regulating HDAC
      phosphorylation and function represent potentially powerful therapeutic
      approaches.

PMID- 17019804
TI  - A novel mechanism of mechanical stress-induced hypertrophy.
AB  - Angiotensin II (AII) type 1 (AT1) receptor plays a critical role in load-induced
      cardiac hypertrophy. We have recently found a novel mechanism of mechanical
      stress-induced activation of the AT1 receptor, which is independent of AII.
      Mechanical stretch did not activate ERKs in HEK293 cells and COS7 cells which had
      no AT1 receptor, but when AT1 receptor was overexpressed in these cells, stretch
      activated ERKs, Galphaq and JAK2. An AT1 receptor blocker, candesartan, inhibited
      stretch-induced activation of ERKs in these cells. Stretch also activated ERKs in
      COS7 cells expressing AT1 mutant which did not bind AII and in cardiac myocytes
      prepared from angiotensinogen null mice. Stretch did not activate ERKs in COS7
      cells which overexpressed ETA receptor and beta-adrenergic receptor. Pressure
      overload induced cardiac hypertrophy in angiotensinogen null mice as well as in
      wild-type mice, which was significantly inhibited by candesartan. These results
      suggest that mechanical stress activates AT1 receptor independently of AII, which
      is inhibited by an inverse agonist candesartan.

PMID- 17019805
TI  - Controlling cardiomyocyte survival.
AB  - Gradually the distinction between signalling pathways originally believed to be
      specific for either hypertrophy, cell cycle control, apoptosis and cell survival
      are fading. The subtle variations in stimuli to a cell and the microenvironment
      will determine cell fate. In cardiomyocytes the entrance into the cell cycle is
      efficiently blocked. Therefore attention has focused on pathways involved in
      hypertrophy to assess effects in ischaemic models and vice versa. Interventions
      at different levels have been shown to be cardiomyocyte protective. Various
      growth factors (including IGF1 and FGF1,2) have shown to prevent or delay
      cardiomyocyte loss in and ex vivo. Similar results have been reported for
      downstream interventions in the signalling pathways. Strong effects after MAPK
      activation have been shown in gene targeted mice. Especially constitutive
      activation of the ERK proteins prevents ischemic damage of the heart with
      conservation of left ventricular function. Evidence for a key role of nuclear Akt
      in preventing apoptosis is accumulating from various genetic and pharmacological
      sources. Development of techniques to measure the level of cardiomyocyte death
      depends on further improvements in molecular imaging in mouse and human. In
      addition to studying cardiomyocyte cell death, it is crucial to measure
      myocardial function. Whether hypertrophy following ischaemia is adaptive or
      maladaptive and whether all apoptosis is detrimental will have to be determined
      by assessment of left ventricular function through invasive and noninvasive
      methods.

PMID- 17019806
TI  - Mechanisms of angiotensin II-dependent progression to heart failure.
AB  - Up-regulation of angiotensin II (AII) signalling plays an important role in the
      pathogenesis of cardiac hypertrophy and failure as evidenced by the efficacy of
      AII receptor blockers or inhibitors of AII biosynthesis in reversing ventricular
      hypertrophy and preventing human heart failure. The mechanisms underlying AII
      action in the heart remain undefined. Myocardial-specific expression of the AII
      type 1 receptor (AT1R) in mice is sufficient for inducing progressive myocyte
      hypertrophy and cardiac remodelling leading to adult heart failure with a disease
      progression course reminiscent of work overload-induced human heart failure. We
      examined the functional, structural and genetic changes associated with disease
      progression in this model. The results reveal that AT1R-dependent interaction
      between myocytes and non-myocytes is critical in cardiac remodelling. At the
      level of cardiomyocytes, decreased mitochondrial function is one of the earliest
      events of AII action leading to mitochondrial depletion and increased apoptosis.
      Up-regulation of cardiac Bcl-2 prevents mitochondrial deterioration,
      cardiomyocyte loss and pathologic remodelling. Importantly, Bcl-2 completely
      rescues premature death due to heart failure and maintains the 'compensated'
      state. The data suggest that targeting Bcl-2 or interfering with mitochondrial
      dysfunction may offer new therapeutic opportunities for preventing transition
      from compensated hypertrophy to heart failure.

PMID- 17019807
TI  - Alterations in myocardial gene expression as a basis for cardiomyopathies and
      heart failure.
AB  - Heart muscle disease and one of its consequences, chronic heart failure, are
      caused by altered gene expression. There are three general types of changes in
      gene expression that can cause or affect the natural history of heart muscle
      disease. These are: (1) mutations in genes that lead to changes in important
      functional properties of proteins critical to myocardial structure and/or
      function; (2) polymorphic variation in disease modifying genes and proteins,
      leading to altered function of a common gene product variant; and (3), regulated
      altered expression of a wild type gene and protein gene product. The role of
      these alterations in gene expression in the cause, progression and interaction
      with therapy of heart muscle disease and heart failure is discussed.

PMID- 17019808
TI  - Role of the insulin-like growth factor 1 (IGF1)/phosphoinositide-3-kinase (PI3K)
      pathway mediating physiological cardiac hypertrophy.
AB  - Growth of the heart can be induced by physiological stimuli (e.g. postnatal
      development or chronic exercise training: 'the athlete's heart') or pathological
      stimuli (e.g. pressure or volume overload). Physiological hypertrophy is
      characterized by the normal organization of sarcomeres and fibres, normal or
      enhanced cardiac function and a relatively normal pattern of cardiac gene
      expression; whereas pathological hypertrophy is associated with an altered
      pattern of cardiac gene expression, fibrosis, cardiac dysfunction and increased
      mortality. Previously, an unresolved question in cardiac biology was whether
      distinct signalling pathways are responsible for the development of pathological
      and physiological cardiac hypertrophy. Recent studies have identified several
      signalling pathways that play unique roles in the regulation of pathological and
      physiological cardiac hypertrophy. This review focuses largely on the role of the
      insulin-like growth factor 1 (IGF1)/phosphoinositide-3-kinase (PI3K) pathway in
      mediating physiological cardiac growth.

PMID- 17019809
TI  - Role of Akt in cardiac growth and metabolism.
AB  - The Akt family of intracellular protein kinases regulates cellular growth,
      proliferation, survival and metabolism. Postnatal growth of the heart chiefly
      involves non-proliferative cardiac myocyte enlargement analogous to skeletal
      muscle growth. Cardiac hypertrophy exists in a 'physiological' form that is an
      adaptive response to long-term exercise training, and as a 'pathological' form
      that is often a maladaptive response to hypertension or valvular heart disease.
      By use of an Akt1-deficient mouse model system, we determined that Akt1 activity
      is required for physiologic cardiac growth in response to insulin-like growth
      factor 1 stimulation or exercise training. In contrast, Akt1 activity was found
      to antagonize pathologic cardiac growth that occurs in response to endothelin 1
      stimulation or pressure overload. Evaluation of an Akt2-deficient mouse model
      system demonstrated that this family member plays an important role in insulin
      stimulated glucose uptake and metabolism, and may not regulate physiologic or
      pathologic cardiac growth. Therefore, Akt1 selectively promotes physiological
      cardiac growth while Akt2 selectively promotes insulin-stimulated cardiac glucose
      metabolism.

PMID- 17019810
TI  - Novel therapy for heart failure and exercise-induced ventricular tachycardia
      based on 'fixing' the leak in ryanodine receptors.
AB  - This review focuses on role played by two modulators of ryanodine receptors
      (RyRs), one a small molecule (1,4-benzothiazepine) and the other a protein
      subunit of the channel (FKBP or calstabin), both of which exert potent effects on
      the channel. These regulators of the RyR channels have potential therapeutic
      implications in that the small molecule and the protein have novel anti
      arrhythmic and anti-heart failure activities involving the cardiac (RyR2) and
      skeletal (RyR1) ryanodine receptors. Protein kinase A (PKA) hyperphosphorylation
      of RyR2 in failing hearts or mutations in RyR2 linked to sudden cardiac death
      (SCD) can result in diastolic sarcoplasmic reticulum (SR) Ca2+ leak that can
      trigger fatal cardiac arrhythmias, and deplete SR Ca2+ stores contributing to
      decreased contractility. We and others have identified a class of small molecules
      derived from 1,4-benzothiazepines, that enhance the binding affinity of calstabin
      2 for RyR2 and reduce the diastolic SR Ca2+ leak, even when the channel is PKA
      hyperphosphorylated. Therefore, this class of compounds has tremendous potential
      as novel therapeutics for heart failure and cardiac arrhythmias.

PMID- 17019811
TI  - Phospholamban as a therapeutic modality in heart failure.
AB  - Increases in diastolic Ca2+ and impaired relaxation in failing hearts have been
      suggested to reflect the deteriorated function of the sarcoplasmic reticulum Ca
      ATPase (SERCA2), whose activity is regulated by phospholamban (PLN). PLN is a
      reversible inhibitor of SERCA2's Ca2+ affinity and cardiac contractility. Studies
      in genetically altered mouse models have demonstrated that the levels and the
      degree of PLN phosphorylation are critical in modulating basal Ca2+ handling and
      contractility. Correspondingly, the depressed contractility in experimental and
      human heart failure is partially attributed to increased inhibition by PLN due
      to: (a) increases in PLN/SERCA2; and (b) decreases in PLN phosphorylation. The
      attenuated PLN phosphorylation is associated with increased type 1 phosphatase,
      which reflects dephosphorylation or inactivation of its inhibitor 1. Indeed PLN
      ablation was successful in rescuing cardiac remodelling and dysfunction in
      several heart failure mouse models, and inhibition of the phosphatase activity
      restored contractile parameters in failing rat hearts. Recently, two human PLN
      mutations, associated with either absence or sustained dephosphorylation of PLN,
      were linked to dilated cardiomyopathy. Thus, PLN modulation appears to be of
      paramount importance in humans, and further investigation into PLN function in
      higher mammalian species may provide insights into its potential as a therapeutic
      modality in heart failure.

PMID- 17019812
TI  - Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac
      myosin heavy chain mutation causing endocardial fibroelastosis and heart failure.
AB  - Inherited human cardiomyopathies often lead to heart failure. A common feature of
      these conditions is that affected individuals can express the disease causing
      mutations for many years without showing clinical signs of the disease. Previous
      studies have demonstrated that sarcomere protein gene mutations can cause either
      dilated cardiomyopathy or hypertrophic cardiomyopathy. Here we demonstrate that
      the Arg442His missense mutation in beta-cardiac myosin heavy chain (betaMHC)
      causes dilated cardiomyopathy, endocardial fibroelastosis and heart failure at a
      very early age. Using standard genetic engineering tools we and others have made
      murine models by introducing human disease causing mutations into mice. The
      central hypothesis of these studies has been that by identifying the
      pathophysiological pathways activated by these mutations we can define enzymatic
      activities that are modified during the disease process and which may be involved
      in pathways that involve more common forms of cardiac disease. Murine models
      bearing different mutant myosins are being used to address whether each disease
      causing mutant betaMHC activates the same or different cellular pathways.
      Dissecting the molecular pathways modulated by mutations in sarcomere protein
      genes as well as other genes has already demonstrated that there are multiple
      pathways leading to cardiac remodelling and heart failure. Defining the
      mechanisms by which mutations in the same genes activate different cellular
      pathways remains an important question.

PMID- 17019813
TI  - The cardiomyocyte cell cycle.
AB  - Many forms of cardiac disease are characterized by cardiomyocyte death due to
      necrosis, apoptosis and/or oncosis. Recently, the notion of promoting cardiac
      regeneration as a means to replace damaged heart tissue has engendered
      considerable interest. One approach to accomplish heart muscle regeneration
      entails promoting cardiomyocyte cell cycle activity in the surviving myocardium.
      Genetically modified mice have provided useful model systems to test the efficacy
      of specific pathways to promote cardiomyocyte proliferation in normal and
      diseased hearts. For example, expression of a heart-restricted dominant
      interfering version of p193 (an E3 ubiquitin ligase also known as Cul7) resulted
      in an induction of cardiomyocyte cell cycle activity at the infarct border zone
      and ventricular septum 4 weeks after permanent coronary artery occlusion. A
      concomitant reduction in hypertrophic cardiomyocyte growth was also observed in
      this model, suggesting that cell cycle activation partially counteracted the
      adverse ventricular remodelling that occurs post-infarction. In other studies,
      targeted expression of cyclin D2 promoted cardiomyocyte cell cycle activity in
      adult hearts. The level of cardiomyocyte cell cycle activity increased after
      myocardial infarction, ultimately resulting in a marked increase in cardiomyocyte
      number and a concomitant regression of infarct size. Collectively, these data
      suggest that modulation of cardiomyocyte cell cycle activity can be exploited to
      promote regenerative growth in injured hearts.

PMID- 17019814
TI  - Restoration of cardiac function with progenitor cells.
AB  - The biological limitations to cardiac regenerative growth create a clinical need
      to promote more efficient cardiac repair. Experimental studies and early-phase
      clinical trials indicate that progenitor cells may be useful as a therapeutic
      tool to improve heart function after myocardial ischaemia. This paper will
      summarize experimental studies to determine (1) the mechanisms underlying
      progenitor cell homing to ischaemic tissue and (2) to define transcription
      factors involved in endothelial maturation of progenitor cells. Homing seems to
      be assisted by a proteolytic enzyme, cathepsin L, which degrades the
      extracellular matrix. In an in vitro assay, a cathepsin inhibitor prevented
      different progenitor cell populations from passing through a matrigel layer. In
      vivo, progenitor cells lacking cathepsin L had an impaired capacity to promote
      neovascularization in ischaemic mouse limbs compared with normal, wild-type
      cells. Differentiation of progenitor cells towards the endothelial phenotype
      involves a member of the homeobox gene family, HoxA9. HoxA9 regulates endothelial
      gene expression (eNOS, KDR, VE-cadherin). Moreover, HoxA9-deficient mice have a
      severe impairment of neovascularization capacity after ischaemia. In the second
      part of the paper, we describe clinical studies using bone marrow or the
      peripheral blood-derived cells for functional recovery of patients with acute and
      chronic heart failure (TOPCARE-AMI, TOPCARE-CHF). Whereas blood-derived and bone
      marrow-derived progenitor cells were equally effective in patients with acute
      myocardial infarction, bone marrow-derived cells were significantly better than
      blood-derived progenitor cells in patients with chronic ischaemic heart disease.

PMID- 17019815
TI  - Signalling pathways in cardiac regeneration.
AB  - Regeneration is a homeostatic mechanism evolved to maintain or restore the
      original architecture of a damaged tissue by recapitulating part of its original
      embryonic development. Our focus has been to intervene in signalling mechanisms
      at work in the regeneration process to increase the efficiency of mammalian
      tissue repair. In response to traumatic injury, both skeletal and cardiac muscle
      activate signalling cascades involved in inflammation, cell death and fibrosis,
      often at the expense of cell survival and regeneration. In contrast, mice
      expressing a local isoform of insulin-like growth factor 1 (mIGF1) as a muscle
      specific transgene maintain skeletal muscle integrity and ageing, counter muscle
      decline in degenerative muscle disease, and show enhanced stem cell homing to
      damaged muscle. Under the control of a cardiac-specific promoter, the mIGF1
      transgene directs efficient repair of infarcted heart tissue without scar
      formation. In both models, novel signalling pathways are employed, suggesting
      specific mechanisms through which mIGF1 improves regeneration and providing
      potential targets for clinical intervention.

PMID- 17019816
TI  - Beyond small molecule drugs for heart failure: prospects for gene therapy.
AB  - For the past several years, the development of new therapeutic agents for chronic
      heart failure (CHF) has been challenged by a number of confounding factors: (1)
      the large number of currently approved therapeutics that have already been shown
      in combination to have a beneficial effect on survival in CHF patients; (2) the
      number of patients required to document survival effects for any new additional
      agent; (3) the need to show a clear-cut effect on survival in mega-trials; (4)
      the chronic nature of the disease which requires long-term therapy with any new
      therapeutic as well as a relatively favourable long-term side effect profile; (5)
      a relative lack of understanding of the pivotal events that drive the onset of
      clinically relevant endpoints in heart failure and that might lead to their
      reversal; and (6) the poor druggability of many potential therapeutic targets for
      CHF. In this regard, recent studies in small animal models have suggested that
      promoting calcium cycling in the failing heart can potentially reverse severe
      heart failure, even at advanced stages. This offers the opportunity to design
      studies to reverse end stage disease, representing a new therapeutic paradigm
      with important implications for clinical trial design. At the same time, recent
      advances in catheter-based gene delivery and third-generation AAV vectors have
      now been shown to allow cardiac restricted, long-term, high efficiency in vivo
      gene delivery and expression in large animal CHF model systems with few long-term
      side effects. Recent collaborative studies from independent groups at the
      Massachusetts General Hospital, the Baker Institute and University of California
      San Diego have now provided direct evidence that manipulation of calcium cycling,
      either via the over-expression of SERCA or the blockade of the SERCA inhibitor
      phospholamban can reverse many important clinical endpoints that are direct
      surrogates of survival in the late stage failing heart. These studies have formed
      the foundation for the initiation of AAV-based gene therapy clinical trials in
      2006-7 in the USA.

PMID- 17019817
TI  - Dual roles of telomerase in cardiac protection and repair.
AB  - Together, the limited capacity for regenerative growth in cardiac muscle after
      injury and the prevalence of ongoing sporadic cell death due to apoptosis in
      chronic heart failure states pose one of the paramount challenges in heart
      failure therapeutics. In adults, the unique self-renewal potential of
      progenitor/stem cells is associated with telomerase reverse transcriptase (TERT),
      an RNA-dependent DNA polymerase that maintains the lariat-like loop capping
      chromosome ends. We have identified telomere uncapping, mediated by down
      regulation of telomere repeat-binding factor 2 (TRF2) as a novel trigger of cell
      death in human dilated cardiomyopathy. Conversely, we identified a residual TERT+
      population in adult myocardium, as a potential source of cardiac progenitor
      cells. Residual TERT expression was localized to cells expressing stem cell
      antigen 1 (Sca1). Cardiac-resident Sca1+ cells lack haematopoietic stem cell
      markers and transcripts for cardiac structural genes, yet express many
      cardiogenic transcription factors. If given intravenously to mice just after
      ischemia-reperfusion injury, cardiac Sca1+ cells home selectively to injured
      myocardium and differentiate spontaneously in situ.

PMID- 17019818
TI  - Working together for better outcomes.

PMID- 17019819
TI  - Competency and capability: imperative for nurse practitioner education.
AB  - OBJECTIVE: The objective of this study was to conduct research to inform the
      development of standards for nurse practitioner education in Australia and New
      Zealand and to contribute to the international debate on nurse practitioner
      practice. SETTING: The research was conducted in all states of Australia where
      the nurse practitioner is authorised and in New Zealand. SUBJECTS: The research
      was informed by multiple data sources including nurse practitioner program
      curricula documents from all relevant universities in Australia and New Zealand,
      interviews with academic convenors of these programs and interviews with nurse
      practitioners. PRIMARY ARGUMENT: Findings from this research include support for
      master's level of education as preparation for the nurse practitioner. These
      programs need to have a strong clinical learning component and in-depth education
      for the sciences of specialty practice. Additionally an important aspect of
      education for the nurse practitioner is the centrality of student directed and
      flexible learning models. This approach is well supported by the literature on
      capability. CONCLUSIONS: There is agreement in the literature about the lack of
      consistent standards in nurse practitioner practice, education and nomenclature.
      The findings from this research contribute to the international debate in this
      area and bring research informed standards to nurse practitioner education in
      Australia and New Zealand.

PMID- 17019820
TI  - Culturaly diverse family members and their hospitalised relatives in acute care
      wards: a qualitative study.
AB  - OBJECTIVE: To describe the experiences of culturally diverse family members who
      make the decision to stay with their relatives in acute care wards. DESIGN: A
      qualitative descriptive study. SETTING: Medical and surgical wards in an acute
      care hospital with a 70% non-English speaking background patient population.
      SUBJECTS: Eight culturally diverse family members who stayed with their
      hospitalised relatives for at least four shifts or the equivalent hours. METHOD:
      In-depth interviews of approximately 45 minutes. FINDINGS: Three main categories
      described the experience of family members. These categories were carrying out in
      hospital roles, adhering to ward rules, and facing concerns. CONCLUSIONS:
      Findings indicate nurses and family members could benefit from negotiating active
      partnerships; family friendly ward environments need to be fostered, supported by
      appropriate policies; and further research is needed into culturally diverse
      family members' partnerships with nurses in acute care settings.

PMID- 17019821
TI  - Cardiac rehabilitation for women: one size does not fit all.
AB  - AIM: To investigate women's perceptions of the contribution of cardiac
      rehabilitation to their recovery from a myocardial infarction. BACKGROUND AND
      PURPOSE: Cardiac rehabilitation programs have been based on research with almost
      exclusively male participants. It was unclear if cardiac rehabilitation programs
      meet the needs of women. METHOD: Ten women who had experienced one or more
      myocardial infarctions were interviewed. Data from these interviews were analysed
      using Glaserian grounded theory. FINDINGS: The core category that emerged from
      the data was 'regaining everydayness'. Participants worked to regain their
      'everydayness' through a basic social process of 'reframing'. Reframing involved
      coming to terms with what they had experienced and fitting it into their lives.
      Other categories related to symptom recognition and recovery. CONCLUSION: Cardiac
      rehabilitation programs contributed to overall recovery from a myocardial
      infarction in different ways for each participant. Although programs provided
      information for participants, they failed to provide the type of support needed
      to effectively aid reframing and recovery. Programs did not meet the needs of all
      participants and it was apparent that one size does not fit all.

PMID- 17019822
TI  - Improving access to clinical information in after hours community palliative
      care.
AB  - OBJECTIVE: To improve access to clinical information for nurses and doctors
      providing after hours community palliative care in a regional Australian setting.
      DESIGN: This was an action research project designed to improve collation and
      distribution of succinct, pertinent and timely information about unstable
      palliative care patients to nurses and general practitioners (GPs) involved in
      after hours care. Each week day, each patient's purpose-designed single-page
      information sheet was updated on the community palliative care service computers.
      This sheet was designed to give key abstracted information on each patient's
      history, current condition, treatment and plans for future care. Patients
      considered to be unstable had their sheets faxed to the GPs on call. SETTING AND
      SUBJECTS: This procedure was followed for all adult patients admitted to Ballarat
      Hospice Care Inc, Victoria, Australia between June and August 2004. The nurses
      and Executive Officer at Ballarat Hospice Care Inc and thirteen GPs from the
      Ballarat and District Division of General Practitioners were involved in the
      study. MAIN OUTCOME MEASURES: Surveys and feedback from palliative care nurses
      and GPs. RESULTS: A one-page information sheet provided essential clinical
      information to nurses and doctors. The nurses' confidence markedly increased with
      ready access to the information sheets on a hand held Palm Pilot. The nurses also
      reported improved outcomes for patients using this approach and there was
      favourable feedback from GPs. CONCLUSIONS: This project led to the development of
      a simple, effective and low cost means of improving communication between
      professionals caring for palliative care patients after hours.

PMID- 17019823
TI  - Assessment and management of chronic pain in the older person living in the
      community.
AB  - AIM: This paper reviews the nursing research literature on chronic pain in the
      older person living in the community and suggests areas for future research.
      BACKGROUND: Chronic pain is a pervasive and complex problem that is difficult to
      treat appropriately. Nurses managing chronic pain in older people in
      domiciliary/home/community nursing settings face many challenges. To provide
      care, the many parameters of chronic pain which include the physical as well as
      the psycho-social impact and the effect of pain on patients and their families,
      must be carefully assessed. Beliefs of the older person about pain and pain
      management are also important. METHOD: Relevant nursing studies were searched
      using CINAHL, Cochrane Database of Systematic Reviews, EMBASE and PUBMED
      databases using key words about pain and the older person that were appropriate
      to each database. RESULTS: Tools to assess pain intensity in the older person
      have been studied but there has been less research on the other parameters of
      pain assessment or how the older person manages pain. An effective nurse-patient
      relationship is an important component of this process and one that needs more
      study. Few research studies have focused on how nurses can be assisted, or on the
      challenges, nurses' face, when managing this vulnerable population. CONCLUSION: A
      broad approach at the organisational level will assist nurses to manage this
      health care issue.

PMID- 17019824
TI  - Nursing sans frontieres: a three year case study of multi-state registration to
      support nursing practice using information technology.
AB  - OBJECTIVE: To highlight the registration issues for nurses who wish to practice
      nationally, particularly those practicing within the telehealth sector. DESIGN:
      As part of a national clinical research study, applications were made to every
      state and territory for mutual recognition of nursing registration and fee waiver
      for telenursing cross border practice for a period of three years. These
      processes are described using a case study approach. OUTCOME: The aim of this
      case study was to achieve registration in every state and territory of Australia
      without paying multiple fees by using mutual recognition provisions and the cross
      border fee waiver policy of the nurse regulatory authorities in order to practice
      telenursing. RESULTS: Mutual recognition and fee waiver for cross-border practice
      was granted unconditionally in two states: Victoria (Vic) and Tasmania (Tas), and
      one territory: the Northern Territory (NT). The remainder of the Australian
      states and territories would only grant temporary registration for the period of
      the project or not at all, due to policy restrictions or nurse regulatory
      authority (NRA) Board decisions. As a consequence of gaining fee waiver the
      annual cost of registration was a maximum of dollars 145 per annum as opposed to
      the potential dollars 959 for initial registration and dollars 625 for annual
      renewal. CONCLUSIONS: Having eight individual nurses Acts and NRAs for a
      population of 265,000 nurses would clearly indicate a case for over regulation in
      this country. The structure of regulation of nursing in Australia is a barrier to
      the changing and evolving role of nurses in the 21st century and a significant
      factor when considering workforce planning.

PMID- 17019825
TI  - The relationship between socioeconomic status and infant mortality in
      metropolitan Ohio, 1999-2001.
AB  - Empirical evidence has consistently documented the direct relationship between
      infant mortality and socioeconomic inequality in the United States and numerous
      other countries. While the majority of these studies reveal an inverse
      relationship between socioeconomic level and infant mortality, not even this
      finding is free from disagreement. Furthermore, the specific nature and magnitude
      of this relationship has varied over time. This study will examine the
      relationship between socioeconomic status and infant mortality in metropolitan
      Ohio by using birth and infant death data centered on the 2000 Census. The
      analyses presented herein will describe and analyze the relationship between
      infant mortality and socioeconomic status in metropolitan Ohio in the year 2000.
      The key finding is that in spite of remarkable declines in infant mortality
      during the past several decades, most notably in neonatal mortality, there
      continues to be a pronounced inverse association between the infant death rate
      and the economic status of a population.

PMID- 17019826
TI  - Structural determinants of child mortality in sub-Saharan Africa: A cross
      national study of economic and social influences from 1970 to 1997.
AB  - This cross-national study seeks to understand the lagging child mortality
      declines in sub-Saharan Africa by using World Bank data to investigate social and
      economic factors at three points in time: 1970, 1985, and 1997. Women's
      education, foreign debt-to-export ratio, and GNP per capita are among the
      strongest correlates of under five mortality over time. Cross-sectional and
      longitudinal results suggest that female education is the best overall predictor
      of child mortality. Average national income does not emerge as a strong
      predictor, particularly since 1985. Increasing levels of foreign debt are
      associated with a substantial excess mortality burden. In 1997, the effect of
      adult HIV prevalence on child mortality was moderate and statistically
      significant. The study concludes that, although future gains in social factors
      such as female education will likely be beneficial, without simultaneously
      addressing high levels of foreign debt and high HIV prevalence, it may be
      difficult to improve child mortality rates across sub-Saharan Africa.

PMID- 17019827
TI  - The heritability of life history strategy: the K-factor, covitality, and
      personality.
AB  - Archival data from the MIDUS survey (Brim et al., 2000), a nationally
      representative sample, on 309 MZ and 333 DZ twin pairs aged 25-74 years were used
      to test the psychometrics and behavioral genetics of life history strategy. We
      organized 253 of the originally administered 2,000 questions into 30 scales
      measuring life history traits (e.g., quality of family relationships and altruism
      towards kin), medical symptoms (e.g., thyroid problems), personality traits
      (e.g., neuroticism, extraversion, conscientiousness), and social background
      (e.g., financial security). A single higher-order factor, indicating a general
      life history strategy, composed of three lower-order factors, was replicated.
      Factor analyses were then performed on the genetic variance-covariance matrices.
      We found that (a) a single higher-order factor explained the preponderance of the
      genetic correlations among the scales and (b) this higher-order factor was itself
      68 percent heritable and accounted for 82 percent of the genetic variance among
      the three component lower-order factors.

PMID- 17019828
TI  - Sex, status, and criminality: a theoretical nexus.
AB  - This article offers a theoretical explanation for relationships between social
      status and involvement in serious and persistent criminal behavior from an
      evolutionary perspective. The theory's central premise is that natural selection
      has produced females who bias their mating choices toward males who strive for
      status. This bias has resulted in males devoting greater time and energy to
      status striving (relative to females). To account for why nearly all
      "victimizing" forms of criminality are more common among males than among
      females, the theory asserts that status striving exists along a continuum of
      competitive/victimizing behavior. One end of this continuum is epitomized by
      crude (criminal) forms of the behavior that societies generally discourage and
      even punish. The other end consists of sophisticated (commercial) forms that
      societies tolerate and even encourage. According to the theory, most males begin
      to exhibit non-playful forms of competitive/victimizing behavior around the onset
      of puberty as they start their reproductive careers. Adolescent males with the
      greatest abilities to learn will transition quickly from crude forms of
      competitive/victimizing behavior to more sophisticated forms, while males who
      have the greatest difficulties learning will transition more slowly. A major
      deduction from the theory is that genes on the Y-chromosome must be affecting the
      brain in ways that promote status-striving behavior. This deduction needs
      empirical scrutiny, although it is consistent with evidence (a) that the Y
      chromosome transforms would-be ovaries into testes, the latter being specialized
      organs for the production of testosterone, and (b) that testosterone alters brain
      functioning in ways that contribute to both status striving and criminality.

PMID- 17019829
TI  - Toward an evolutionary forensic psychology.
AB  - Most theories of crime have not explored intensively biological and especially
      evolutionary explanations for criminal behavior. Ellis presents a valuable new
      perspective that proposes that attention to physiological mechanisms shaped by
      evolutionary forces can provide insights into the causes of crime and sex
      differences in the patterns of crime. We discuss other theories and research
      relevant to Ellis' theory. We also propose that an evolutionary psychological
      perspective of crime will help to invigorate research and lead to a better
      understanding of criminality. An integrated evolutionary forensic psychology will
      help to explain sources of conflict between individuals, situations in which
      conflict leads to victimization, and victim defenses and coping mechanisms.

PMID- 17019830
TI  - Comments on: "Sex, status, and criminality: a theoretical nexus.

PMID- 17019832
TI  - The Bourgeois-Pichat's biometric method and the influence of climate: new
      evidences from late 19th-century Italy.
AB  - This paper examines to which extent seasonal and climatic conditions might affect
      the reliability of the Bourgeois-Pichat's method. Other scholars have already
      argued on this issue, but although climate has often been claimed to explain part
      of the differentials in mortality figures among Italian regions, to date its
      impact has not actually been recognized and quantitatively evaluated. To test
      such hypothesis data at the regional level from late 19th-century Italy have been
      analyzed. Our analysis of the biometric components revealed a strong bias in the
      estimates of the endogenous and exogenous components in the first month of life.
      Variations in infant mortality among Italian regions correlated with variations
      in the endogenous levels rather than in the exogenous levels of infant (neonatal)
      mortality, as it was expected owing to the infective nature of the diseases
      climate might induce. Specifically, Northern and colder regions featured high
      figures for both neonatal mortality and the endogenous component, while the
      opposite scheme applied to the Southern, more temperate regions. Finally, the
      reasons for such misleading results were investigated. It emerged that the
      model's assumption of a constant and invariant proportion of neonatal exogenous
      deaths to the total amount of exogenous deaths was not matched by the Italian
      data. This situation caused the excess neonatal exogenous mortality, especially
      that induced by cold climate in Northern regions, to be wrongly counted in the
      endogenous component.

PMID- 17019831
TI  - Psychological factors as mechanisms for socioeconomic disparities in health: a
      critical appraisal of four common factors.
AB  - Social epidemiology has increasingly looked to psychological factors as both risk
      factors for physical health and mechanisms behind disparities. Yet, there has
      been little resolution to the question of whether psychological factors explain
      disparities, and skepticism has begun to mount about whether psychological
      factors are causally linked to health. Furthermore, some have questioned the
      nature of the relationship: most research suggests that psychological factors
      mediate the relationship between socioeconomic status and health, but recent
      research suggests that they moderate the relationship. The present paper attempts
      to provide a more comprehensive appraisal of the current debate. It uses four
      popular psychological factors (i.e., self-esteem, mastery, neuroticism, and
      depressive symptoms), three health outcomes, and a nationally representative,
      three-panel longitudinal survey. The results illustrate the promise and
      limitations of psychological mechanisms. In the cross-section, the results
      provide evidence for substantial moderating effects, but these effects disappear
      entirely when estimated prospectively. The results also provide some evidence for
      mediating effects, but these effects are very weak and the prospective effects of
      psychological factors diminish over time and with controls for baseline health.
      Implications for theories of socioeconomic status and health are discussed and a
      more social psychologically sophisticated approach is encouraged.

PMID- 17019833
TI  - Immigration and Chinese reproductive behavior in Canada.
AB  - This study is intended to provide an empirical testing of the minority status
      hypothesis with regard to the fertility behavior of Chinese immigrants to Canada.
      The focus is placed on the role of group or social context on actions of
      individuals. Factors incurred in the immigration process as explained by
      disruption and assimilation hypotheses are also examined. Using the multi-level
      contextual analysis, we have found that the relative economic insecurity that
      comes from minority membership and the course of immigration serves to decrease
      fertility of minority members, whether they are associated with a pronatalist
      heritage or not. However, pronatalist traditions do stimulate fecundity of
      Chinese immigrants as long as their relative economic status is improved and the
      hardship is gone.

PMID- 17019834
TI  - Required parental investment and mating patterns: a quantitative analysis in the
      context of evolutionarily stable strategies.
AB  - Much social psychological research has been dedicated to understanding mating
      strategies from the standpoint of genetic-fitness payout (e.g., Simpson and
      Gangestad, 2000). The current work is designed to provide a coherent,
      quantitative model for predicting different classes of mating strategies in both
      males and females. Specifically, the framework developed in this paper is an
      elaboration of Dawkins' (1989) quantitative assessment of different male and
      female mating strategies. Dawkins suggests that the prevalence of different
      strategies employed should be predictable in terms of evolutionary stable
      strategies. In the current work, a quantitative analysis predicting the
      prevalence of different mating strategies within each sex was conducted. The
      mathematical functions derived suggest that variability in the costs associated
      with raising offspring affects the expected prevalence of mating strategies
      differently for males and females. According to the present model, variability in
      female strategies should be less affected by changes in parental investment (PI)
      than variability in male strategies. Important predictions regarding male and
      female mating strategies across cultures are discussed.

PMID- 17019835
TI  - Sex ratio at birth, polygyny, and fertility: a cross-national study.
AB  - The sex ratio at birth may reflect frequency of intercourse that affects the
      timing of conception. If so, cross-national variation in polygyny and fertility
      might account for country differences in secondary sex ratios. Consistent with
      the timing of intercourse hypothesis, the birth sex ratios of 148 countries
      declined with total fertility rates and polygyny intensity, and increased with
      contraception use in correlational analysis. Regression analysis confirmed that
      polygyny was a negative predictor of the sex ratio (and contraception was a
      positive predictor), with level of economic development and mother's age
      controlled, but the effects disappeared with total fertility added to the
      equation. The sex ratio evidently declines with increases in fertility because
      more children are born at a later birth order when frequency of intercourse is
      lower.

PMID- 17019836
TI  - [Antihypertensive agents used as first line agents: beta-blockers under
      pressure].

PMID- 17019837
TI  - [Initial management of hypertension in a primary care service].
AB  - The management of hypertension in Switzerland follows the Guidelines of the
      European Society of Hypertension and Cardiology (ESH-ESC 2003). The aim of our
      survey was to evaluate to what extent initial check-up and determination of the
      absolute cardiovascular risk of hypertensive patients are performed by residents
      of a medical outpatient clinic. Hypertension is a very frequent condition in this
      kind of consultation, 1 patient in 3 being treated for a high blood pressure.
      Despite of this, the initial evaluation of the absolute cardiovascular risk is
      not performed in accordance with the guidelines. The assessment of diabetes or
      dyslipidemia and the search for target organ damage are not systematically done,
      even in case of high blood pressure values (grade I-III).

PMID- 17019838
TI  - [Clinical implications of central blood pressure].
AB  - The diagnosis and the treatment of hypertension are based on blood pressure
      readings traditionally taken at the level of the brachial artery. It is currently
      possible to determine central blood pressure using the aplanation tonometry
      technique and applying a transfer function to calculate the impact of reflecting
      waves on pressure prevailing in thoracic aorta. The reflected waves which reach
      the thoracic aorta in systole are more marked when the stiffness of the arterial
      wall is increased, leading to augmentation of central systolic blood pressure.
      Recent clinical trials have shown that, for the same decrease in peripheral blood
      pressure, different therapeutic strategies do not necessarily impact identically
      on central blood pressure. This fact might influence their ability to prevent
      cardiovascular complications.

PMID- 17019839
TI  - [High blood pressure and alcohol consumption].
AB  - The possible effects of individual alcoholic beverages on blood pressure continue
      to arouse interest. There is a positive relationship between alcohol intake and
      blood pressure. The nature of this relationship still remains unresolved. Authors
      led studies where different patterns of drinking were assessed. First, different
      mechanisms are involved for generating hypertension when alcohol drinking.
      Vasoconstriction effects and modification of smooth muscles are well established
      factors of alcohol-induced hypertension. Calcium movements are also involved. Men
      and women are affected by hypertensive effects of excessive alcohol consumption.
      Drinking alcohol during meals is a probable protective factor of developing
      hypertension. Reducing alcohol consumption provokes a significant diminution of
      hypertension.

PMID- 17019840
TI  - [Lercanidipine, a third generation calcium antagonist. Which advantages?].
AB  - Lercanidipine is a new highly lipophylic dihydropyrdine derivative of the third
      generation with equal efficacy but an improved tolerability profile. Comparative
      therapeutic trials have shown that it is as effective as other dihydropyridines,
      in particular amlodipine, beta-blockers, and angiotensin-converting enzyme
      inhibitors. Lercanidipine is well tolerated, with most treatment-emergent events
      related to vasodilation. Lercanidipine produces less reflex tachycardia and
      peripheral oedema. Common adverse events included headache and flushing. Because
      of its efficacy and favorable safety profile, lercanidipine has the potential to
      improve blood pressure control in a wide range of patients, including those who
      have not responded to, or who have been unable to tolerate other antihypertensive
      agents.

PMID- 17019841
TI  - [The revived interest in aldosterone antagonists].
AB  - Aldosterone plays a pivotal role in sodium and water homeostasis, in particular
      in patients with heart failure or high blood pressure. These medications, when
      used on top of a standard therapy, improve the outcome of patients with heart
      failure and are also effective in lowering blood pressure of hypertensive
      patients. The major risk associated with the use of these antagonists is
      hyperkalemia, which can be prevented in avoiding their prescription in patients
      with impaired renal function. Eplerenone has the advantage, compared with
      spironolactone, to be better tolerated in terms of "hormonal" adverse effects.

PMID- 17019842
TI  - [Cervicogenic headaches].
AB  - Cervicogenic headaches are a relatively new nosological entity. The diagnostic
      criteria are still under discussion. They are rare: the diagnostic is based on
      anamnestic and clinical considerations. Rx investigation is mandatory. The
      aetiology is multifactorial. In case of cervical trauma, the relationship with
      the primary peripheral lesion must be carefully discussed. The actual opinion
      from the neurophysiological point of view is based on the hypothesis of "central
      hypersensitivity". This progressive dysfunction is probably modulated by genetic
      characteristics: the mechanism is triggered by the initial peripheral nociceptive
      input. In chronic situations, psychosocial factors are important. The treatment
      must be considered individually. It is based on a pharmacological approach and,
      in selected cases, includes anaesthetic block.

PMID- 17019843
TI  - [The physician's role, a privileged player in front of terrorism].

PMID- 17019844
TI  - [Clostridium difficile:an epidemic event in service of public health].

PMID- 17019845
TI  - [The year 2006, between cloning and gene doping].

PMID- 17019846
TI  - [A small diverse fact opens up the great world].

PMID- 17019847
TI  - [Circadian metabolism of medicaments: an important Geneva discovery].

PMID- 17019848
TI  - [The abandonment of an utopia].

PMID- 17019849
TI  - Extended kalman filtering for the modeling and analysis of ICG pharmacokinetics
      in cancerous tumors using NIR optical methods.
AB  - Compartmental modeling of indocyanine green (ICG) pharmacokinetics, as measured
      by near infrared (NIR) techniques, has the potential to provide diagnostic
      information for tumor differentiation. In this paper, we present three different
      compartmental models to model the pharmacokinetics of ICG in cancerous tumors. We
      introduce a systematic and robust approach to model and analyze ICG
      pharmacokinetics based on the extended Kalman filtering (EKF) framework. The
      proposed EKF framework effectively models multiple-compartment and multiple
      measurement systems in the presence of measurement noise and uncertainties in
      model dynamics. It provides simultaneous estimation of pharmacokinetic parameters
      and ICG concentrations in each compartment. Moreover, the recursive nature of the
      Kalman filter estimator potentially allows real-time monitoring of time varying
      pharmacokinetic rates and concentration changes in different compartments.
      Additionally, we introduce an information theoretic criteria for the best
      compartmental model order selection, and residual analysis for the statistical
      validation of the estimates. We tested our approach using the ICG concentration
      data acquired from four Fischer rats carrying adenocarcinoma tumor cells. Our
      study indicates that, in addition to the pharmacokinetic rates, the EKF model may
      provide parameters that may be useful for tumor differentiation.

PMID- 17019850
TI  - Surface-source modeling and estimation using biomagnetic measurements.
AB  - We propose a number of electric source models that are spatially distributed on
      an unknown surface for biomagnetism. These can be useful to model, e.g., patches
      of electrical activity on the cortex. We use a realistic head (or another organ)
      model and discuss the special case of a spherical head model with radial sensors
      resulting in more efficient computations of the estimates for
      magnetoencephalography. We derive forward solutions, maximum likelihood (ML)
      estimates, and Cramer-Rao bound (CRB) expressions for the unknown source
      parameters. A model selection method is applied to decide on the most appropriate
      model. We also present numerical examples to compare the performances and
      computational costs of the different models and illustrate when it is possible to
      distinguish between surface and focal sources or line sources. Finally, we apply
      our methods to real biomagnetic data of phantom human torso and demonstrate the
      applicability of them.

PMID- 17019851
TI  - Estimation of number of independent brain electric sources from the scalp EEGs.
AB  - In electromagnetic source analysis, many source localization strategies require
      the number of sources as an input parameter (e.g., spatio-temporal dipole fitting
      and the multiple signal classification). In the present study, an information
      criterion method, in which the penalty functions are selected based on the spatio
      temporal source model, has been developed to estimate the number of independent
      dipole sources from electromagnetic measurements such as the electroencephalogram
      (EEG). Computer simulations were conducted to evaluate the effects of various
      parameters on the estimation of the source number. A three-concentric-spheres
      head model was used to approximate the head volume conductor. Three kinds of
      typical signal sources, i.e., the damped sinusoid sources, sinusoid sources with
      one frequency band and sinusoid sources with two separated frequency bands, were
      used to simulate the oscillation characteristics of brain electric sources. The
      simulation results suggest that the present method can provide a good estimate of
      the number of independent dipole sources from the EEG measurements. In addition,
      the present simulation results suggest that choosing the optimal penalty function
      can successfully reduce the effect of noise on the estimation of number of
      independent sources. The present study suggests that the information criterion
      method may provide a useful means in estimating the number of independent brain
      electrical sources from EEG/MEG measurements.

PMID- 17019852
TI  - Data-guided brain deformation modeling: evaluation of a 3-D adjoint inversion
      method in porcine studies.
AB  - Biomechanical models of brain deformation are useful tools for estimating
      parenchymal shift that results during open cranial procedures. Intraoperative
      data is likely to improve model estimates, but incorporation of such data into
      the model is not trivial. This study tests the adjoint equations method (AEM) for
      data assimilation as a viable approach for integrating displacement data into a
      brain deformation model. AEM was applied to two porcine experiments. AEM-based
      estimates were compared both to measured displacement data [from computed
      tomography (CT) scans] and to model solutions obtained without the guidance of
      sparse data, which we term the best prior estimate (BPE). Additionally, the
      sensitivity of the AEM solution to inverse parameter selection was investigated.
      The results suggest that it is most important to estimate the size of the
      variance in the measurement error correctly, make the correlation length long and
      estimate displacement (over stress) boundary conditions. Application of AEM shows
      an average 33% improvement over BPE. This paper represents the first evidence of
      successful use of the AEM technique in three dimensions with experimental data
      validation. The guidelines established for selection of model parameters are
      starting points for further optimization of the method under clinical conditions.

PMID- 17019853
TI  - Experimental evidence of improved transthoracic defibrillation with
      electroporation-enhancing pulses.
AB  - There is considerable work on defibrillation wave form optimization. This paper
      determines the impedance changes during defibrillation, then uses that
      information to derive the optimum defibrillation wave form. METHODS PART I:
      Twelve guinea pigs and six swine were used to measure the current wave form for
      square voltage pulses of a strength which would defibrillate about 50% of the
      time. In guinea pigs, electrodes were placed thoracically, abdominally and
      subcutaneously using two electrode materials (zinc and steel) and two electrode
      pastes (Core-gel and metallic paste). RESULTS PART I: The measured current wave
      form indicated an exponentially increasing conductance over the first 3 ms,
      consistent with enhanced electroporation or another mechanism of time-dependent
      conductance. We fit this current with a parallel conductance composed of a time
      independent component (g0 = 1.22 +/- 0.28 mS) and a time-dependent component
      described by g delta (1-e(-t/tau)), where g delta = 0.95 +/- 0.20 mS and tau =
      0.82 +/- 0.17 ms in guinea pigs using zinc and Cor-gel. Different electrode
      placements and materials had no significant effect on this fit. From our fit, we
      determined the stimulating wave form that would theoretically charge the
      myocardial membrane to a given threshold using the least energy from the
      defibrillator. The solution was a very short, high voltage pulse followed
      immediately by a truncated ascending exponential tail. METHODS PART II: The
      optimized wave forms and similar nonoptimized wave forms were tested for efficacy
      in 25 additional guinea pigs and six additional swine using methods similar to
      Part I. RESULTS PART II: Optimized wave forms were significantly more efficacious
      than similar nonoptimized wave forms. In swine, a wave form with the short pulse
      was 41% effective while the same wave form without the short pulse was 8.3%
      effective (p < 0.03) despite there being only a small difference in energy (111 J
      versus 116 CONCLUSIONS: We conclude that a short pulse preceding a defibrillation
      pulse significantly improves efficacy, perhaps by enhancing electroporation.

PMID- 17019854
TI  - Modelling and evaluation of surgical performance using hidden Markov models.
AB  - Minimally invasive surgery has become very widespread in the last ten years.
      Since surgeons experience difficulties in learning and mastering minimally
      invasive techniques, the development of training methods is of great importance.
      While the introduction of virtual reality-based simulators has introduced a new
      paradigm in surgical training, skill evaluation methods are far from being
      objective. This paper proposes a method for defining a model of surgical
      expertise and an objective metric to evaluate performance in laparoscopic
      surgery. Our approach is based on the processing of kinematic data describing
      movements of surgical instruments. We use hidden Markov model theory to define an
      expert model that describes expert surgical gesture. The model is trained on
      kinematic data related to exercises performed on a surgical simulator by
      experienced surgeons. Subsequently, we use this expert model as a reference model
      in the definition of an objective metric to evaluate performance of surgeons with
      different abilities. Preliminary results show that, using different topologies
      for the expert model, the method can be efficiently used both for the
      discrimination between experienced and novice surgeons, and for the quantitative
      assessment of surgical ability.

PMID- 17019855
TI  - Multifractal ECG mapping of ventricular epicardium during regional ischemia in
      the pig.
AB  - Myocardial ischemia creates abnormal electrophysiological substrates that can
      result in life-threatening ventricular arrhythmias. Early clinical identification
      of ischemia in patients is important to managing their condition. We analyzed
      electrograms from an ischemia-reperfusion animal model in order to investigate
      the relationship between myocardial ischemia and variability of electrocardiogram
      (ECG) multifractality. Ventricular epicardial electropotential maps from the
      anesthetized pig during LAD ischemia-reperfusion were analyzed using multifractal
      methods. A new parameter called the singularity spectrum area reference
      dispersion (SARD) is presented to represent the temporal evolution of
      multifractality. By contrasting the ventricular epicardial SARD and range of
      singularity strength (delta alpha) maps against activation-recovery interval
      (ARI) maps, we found that the dispersions of SARD and dleta alpha increased
      following the onset of ischemia and decreased with tissue recovery. In addition,
      steep spatial gradients of SARD and delta alpha corresponded to locations of
      ischemia, although the distribution of multifractality did not reflect the degree
      of myocardial ischemia. However, the multifractality of the ventricular
      epicardial electrograms was useful for classifying the recoverability of ischemic
      tissue. Myocardial ischemia significantly influenced the multifractality of
      ventricular electrical activity. Recoverability of ischemic myocardium can be
      classified using the multifractality of ventricular epicardial electrograms. The
      location and size of regions of severe ischemic myocardium with poor
      recoverability is detectable using these methods.

PMID- 17019856
TI  - Simulation of intramuscular EMG signals detected using implantable myoelectric
      sensors (IMES).
AB  - The purpose of this study was to test the feasibility of recording independent
      electromyographic (EMG) signals from the forearm using implantable myoelectric
      sensors (IMES), for myoelectric prosthetic control. Action potentials were
      simulated using two different volume conductor models: a finite-element (FE)
      model that was used to explore the influence of the electrical properties of the
      surrounding inhomogeneous tissues and an analytical infinite volume conductor
      model that was used to estimate the approximate detection volume of the implanted
      sensors. Action potential amplitude increased progressively as conducting
      electrodes, the ceramic electrode casing and high resistivity encapsulation
      tissue were added to the model. For the muscle fiber locations examined, the mean
      increase in EMG root mean square amplitude when the full range of material
      properties was included in the model was 18.2% (+/-8.1%). Changing the
      orientation of the electrode with respect to the fiber direction altered the
      shape of the electrode detection volume and reduced the electrode selectivity.
      The estimated detection radius of the IMES electrode, assuming a cylindrical
      muscle cross section, was 4.8, 6.2, and 7.5 mm for electrode orientations of 0
      degree, 22.5 degrees, and 45 degrees with respect to the muscle fiber direction.

PMID- 17019857
TI  - Automated diagnostic systems with diverse and composite features for Doppler
      ultrasound signals.
AB  - In this paper, we present the automated diagnostic systems for Doppler ultrasound
      signals classification with diverse and composite features and determine their
      accuracies. We compared the classification accuracies of six different
      classifiers, namely multilayer perceptron neural network (MLP), combined neural
      network (CNN), mixture of experts (ME), modified mixture of experts (MME),
      probabilistic neural network (PNN), and support vector machine (SVM), which were
      trained on diverse or composite features. The present study was conducted with
      the purpose of answering the question of whether the automated diagnostic systems
      improve the capability of classification of ophthalmic arterial (OA) and internal
      carotid arterial (ICA) Doppler signals. Our research demonstrated that the SVM
      trained on composite feature and the MME trained on diverse features achieved
      accuracy rates which were higher than that of the other automated diagnostic
      systems.

PMID- 17019858
TI  - Dimensionality reduction of a pathological voice quality assessment system based
      on Gaussian mixture models and short-term cepstral parameters.
AB  - Voice diseases have been increasing dramatically in recent times due mainly to
      unhealthy social habits and voice abuse. These diseases must be diagnosed and
      treated at an early stage, especially in the case of larynx cancer. It is widely
      recognized that vocal and voice diseases do not necessarily cause changes in
      voice quality as perceived by a listener. Acoustic analysis could be a useful
      tool to diagnose this type of disease. Preliminary research has shown that the
      detection of voice alterations can be carried out by means of Gaussian mixture
      models and short-term mel cepstral parameters complemented by frame energy
      together with first and second derivatives. This paper, using the F-Ratio and
      Fisher's discriminant ratio, will demonstrate that the detection of voice
      impairments can be performed using both mel cesptral vectors and their first
      derivative, ignoring the second derivative.

PMID- 17019859
TI  - Extracting fuzzy rules from polysomnographic recordings for infant sleep
      classification.
AB  - A neuro-fuzzy classifier (NFC) of sleep-wake states and stages has been developed
      for healthy infants of ages 6 mo and onward. The NFC takes five input patterns
      previously identified on 20-s epochs from polysomnographic recordings and assigns
      them to one out of five possible classes: Wakefulness, REM-Sleep, Non-REM Sleep
      Stage 1, Stage 2, and Stage 3-4. The definite criterion for a sleep state or
      stage to be established is duration of at least 1 min. The data set consisted of
      a total of 14 continuous recordings of naturally occurring naps (average
      duration: 143 +/- 39 min), corresponding to a total of 6021 epochs. They were
      divided in a training, a validation and a test set with 7, 2, and 5 recordings,
      respectively. During supervised training, the system determined the fuzzy
      concepts associated to the inputs and the rules required for performing the
      classification, extracting knowledge from the training set, and pruning
      nonrelevant rules. Results on an independent test set achieved 83.9 +/- 0.4% of
      expert agreement. The fuzzy rules obtained from the training examples without a
      priori information showed a high level of coincidence with the crisp rules stated
      by the experts, which are based on internationally accepted criteria. These
      results show that the NFC can be a valuable tool for implementing an automated
      sleep-wake classification system.

PMID- 17019860
TI  - Estimation of motor unit conduction velocity from surface EMG recordings by
      signal-based selection of the spatial filters.
AB  - Muscle fiber conduction velocity (CV) can be estimated by the application of a
      pair of spatial filters to surface electromagnetic (EMG) signals and compensation
      of the spatial filter transfer function with equivalent temporal filters. This
      method integrates the selection of the spatial filters for signal detection to
      the estimation of CV. Using this approach, in this paper, we propose a novel
      technique for signal-based selection of the spatial filter pair that minimizes
      the effect of nonpropagating signal components (end-of-fiber effects) on CV
      estimates (optimal filters). The technique is applicable to signals with one
      propagating and one nonpropagating component, such as single motor unit action
      potentials. It is shown that the determination of the optimal filters also allows
      the identification of the propagating and nonpropagating signal components. The
      new method was applied to simulated and experimental EMG signals. Simulated
      signals were generated by a cylindrical, layered volume conductor model.
      Experimental signals were recorded from the abductor pollicis brevis with a
      linear array of 16 electrodes. In the simulations, the proposed approach provided
      CV estimates with lower bias due to nonpropagating signal components than
      previously proposed methods based on the entire signal waveform. In the
      experimental signals, the technique separated propagating and nonpropagating
      signal components with an average reconstruction error of 2.9 +/- 0.9% of the
      signal energy. The technique may find application in single motor unit studies
      for decreasing the variability and bias of CV estimates due to the presence and
      different weights of the nonpropagating components.

PMID- 17019861
TI  - A granular description of ECG signals.
AB  - In this paper, we develop a general framework of a granular representation of ECG
      signals. The crux of the approach lies in the development and ongoing processing
      realized in the setting of information granules-fuzzy sets. They serve as basic
      conceptual and semantically meaningful entities using which we describe signals
      and build their models (such as various predictive schemes or classifiers). A
      comprehensive two-phase scheme of the design of the information granules is
      proposed and described. At the first phase, we discuss the temporal granulation
      through a series of temporal windows (granular windows) and an aggregation of the
      values of signal by means of fuzzy sets. To address this issue, offered is a
      detailed method of building a fuzzy set based on numeric data and a certain
      optimization criterion that strikes a balance between the highest experimental
      relevance of the fuzzy set supported by numeric data and its substantial
      specificity. At the next phase of the granular design, a collection of
      information granules is further summarized with the use of fuzzy clustering
      (Fuzzy C-Means). The resulting prototypes (centroids) formed by this grouping
      process serve as elements of the granular vocabulary. We discuss ways of using
      these vocabularies in the knowledge-based representation, modeling, and
      classification of ECG beats.

PMID- 17019862
TI  - Prediction of intrauterine pressure from electrohysterography using optimal
      linear filtering.
AB  - We propose a method of predicting intrauterine pressure (IUP) from external
      electrohysterograms (EHG) using a causal FIR Wiener filter. IUP and 8-channel EHG
      data were collected simultaneously from 14 laboring patients at term, and
      prediction models were trained and tested using 10-min windows for each patient
      and channel. RMS prediction error varied between 5-14 mmHg across all patients.
      We performed a 4-way analysis of variance on the RMS error, which varied across
      patients, channels, time (test window) and model (train window). The patient
      channel interaction was the most significant factor while channel alone was not
      significant, indicating that different channels produced significantly different
      RMS errors depending on the patient. The channel-time factor was significant due
      to single-channel bursty noise, while time was a significant factor due to
      multichannel bursty noise. The time-model interaction was not significant,
      supporting the assumption that the random process generating the IUP and EHG
      signals was stationary. The results demonstrate the capabilities of optimal
      linear filter in predicting IUP from external EHG and offer insight into the
      factors that affect prediction error of IUP from multichannel EHG recordings.

PMID- 17019863
TI  - Motion estimation in ultrasound images using time domain cross correlation with
      prior estimates.
AB  - In this paper we introduce a new speckle tracking method that is based on the
      standard time-domain cross correlation strain estimation (TDE). We call this
      method time-domain cross-correlation with prior estimates (TDPE), because it uses
      prior displacement estimates of neighboring windows to speed up computation. TDPE
      has all the advantages of TDE, but is much faster. Simulations, as well as
      experiments with phantoms and tissue, indicate that TDPE is capable of reliably
      estimating tissue displacement and strain over a large range of displacements in
      real time. The computational efficiency of TDPE is compared with current time
      efficient methods that have been used in real time strain imaging systems. The
      results show that TDPE is the most time efficient algorithm to date, and is
      roughly 10 times faster than the TDE. The implementation of TDPE on an Ultrasonix
      RP500 ultrasound machine runs at 30 fps for strain images of 16000 pixels.

PMID- 17019864
TI  - Constrained least squares filtering algorithm for ultrasound image deconvolution.
AB  - A new medical ultrasound tissue model is considered in this paper, which
      incorporates random fluctuations of the tissue response and provides more
      realistic interpretation of the received pulse-echo ultrasound signal. Using this
      new model, we propose an algorithm for restoration of the degraded ultrasound
      image. The proposed deconvolution is a modification of the classical
      regularization technique which combines Wiener filter and the constrained least
      squares (LS) algorithm for restoration of the ultrasound image. The performance
      of the algorithm is evaluated based on both the simulated phantom images and real
      ultrasound radio frequency (RF) data. The results show that the algorithm can
      provide improved ultrasound imaging performance in terms of the resolution gain.
      The deconvolved images visually show better resolved tissue structures and reduce
      speckle, which are confirmed by a medical expert.

PMID- 17019865
TI  - Forecasting the unresponsiveness to verbal command on the basis of EEG frequency
      progression during anesthetic induction with propofol.
AB  - The objective of this study is to model the association between the
      electroencephalogram (EEG) spectral features and the novel r scale representing
      the sedative effects of the propofol anesthetic drug. On the basis of the r
      scale, the unresponsiveness to the verbal command (LVC) is forecasted. EEG
      recordings are taken from a 16-patient study population undergoing propofol
      anesthetic induction. EEG was filtered into consecutive 4-Hz passbands up to 28
      Hz. Of these time-series, the amplitude envelopes were extracted and used as
      input features to the first and the second-order polynomial multiple linear
      regression models. The values r epsilon [0.4, 1] were predicted with the R2 value
      of 0.775 with a cross validation. The LVC times were forecasted with the median
      error of 5%-7% or equivalently 10-13 s. In contrast, using the median of the
      measured LVC times of the training population as a forecast, the corresponding
      error was 12% or 26 s. The results suggest an acceptable correlation between the
      r scale and the EEG spectrum in the studied range. Moreover, the r values of an
      individual can be predicted using a population model. The suggested framework
      enables forecasting the LVC, which may open new possibilities for steering the
      drug administration.

PMID- 17019866
TI  - Latency detection in motor responses: a model-based approach with genetic
      algorithm optimization.
AB  - The latency of a response is one of the most frequently reported parameters when
      describing the characteristics of a motor system. Such measurement provides
      important information both to the basic researcher investigating the neural
      circuitry of the underlying physiological system and to the clinician gathering
      information for diagnosing a patient. Our concern here is that when the latency
      of a response is determined on experimentally recorded data by using the most
      commonly referenced techniques to find the onset of a motor response, the
      resulting figure encompasses both the neural processing time and the dynamics of
      the system producing the response (e.g., the musculoskeletal apparatus).
      Therefore, the resulting latency measurement cumulates information relative to
      two substantially different sources and thus having different implications. The
      goal of our study is that of suggesting a technique allowing the separation of
      the relative contributions of neural transmission and processing time from that
      of the dynamics of the motor system. This is accomplished by using a technique
      based on fitting a model to the experimentally recorded response, thus allowing
      to exploit as much as is known with regards to the dynamics of the studied motor
      system (e.g., model order and constraints on the values of the model parameters).
      The optimization of the model parameters for fitting the experimental data is
      carried out using a real-valued genetic algorithm, allowing to avoid trapping in
      local, suboptimal minima. The use of this approach allows to estimate the pure
      delay in the response introduced by neural processing more accurately than the
      traditional latency detection techniques based on adaptive thresholds.

PMID- 17019867
TI  - Improved performance of bayesian solutions for inverse electrocardiography using
      multiple information sources.
AB  - The usual goal in inverse electrocardiography (ECG) is to reconstruct cardiac
      electrical sources from body surface potentials and a mathematical model that
      relates the sources to the measurements. Due to attenuation and smoothing that
      occurs in the thorax, the inverse ECG problem is ill-posed and imposition of a
      priori constraints is needed to combat this ill-posedness. When the problem is
      posed in terms of reconstructing heart surface potentials, solutions have not yet
      achieved clinical utility; limitations include the limited availability of good a
      priori information about the solution and the lack of a "good" error metric. We
      describe an approach that combines body surface measurements and standard forward
      models with two additional information sources: statistical prior information
      about epicardial potential distributions and sparse simultaneous measurements of
      epicardial potentials made with multielectrode coronary venous catheters. We
      employ a Bayesian methodology which offers a general way to incorporate these
      information sources and additionally provides statistical performance analysis
      tools. In a simulation study, we first compare solutions using one or more of
      these information sources. Then, we study the effects of varying the number of
      sparse epicardial potential measurements on reconstruction accuracy. To evaluate
      accuracy, we used the Bayesian error covariance as well as traditional error
      metrics such as relative error. Our results show that including even sparsely
      sampled information from coronary venous catheters can substantially improve the
      reconstruction of epicardial potential distributions and that a Bayesian
      framework provides a feasible approach to using this information. Moreover,
      computing the Bayesian error standard deviations offers a means to indicate
      confidence in the results even in the absence of validation data.

PMID- 17019868
TI  - Automatic adaptive enhancement for images obtained with fiberscopic endoscopes.
AB  - Modern techniques for medical diagnostics and therapy in keyhole surgery
      scenarios as well as technical inspection make use of flexible endoscopes. Their
      characteristic bendable image conductor consists of a very limited number of
      coated fibers, which leads to so-called comb structure. This effect has a
      negative impact on further image processing steps such as feature tracking
      because these overlaid image structures are wrongly detected as image features.
      With respect to these tasks, we propose an automatic approach to generate optimal
      spectral filter masks for enhancement of fiberscopic images. We apply the Nyquist
      Shannon sampling theorem to the spectrum of fiberscopically acquired images to
      obtain parameters for optimal filter mask calculation. This can be done
      automatically and independently of scale and resolution of the image conductor as
      well as type and resolution of the image sensor. We designed and verified simple
      rotation invariant masks as well as star-shaped rotation variant masks that
      contain information about orientation between the fiberscope and sensor. A
      subjective survey among experts between different modes of filtering certified
      the best results to the adapted star-shaped mask for high-quality glass
      fiberscopes. We furthermore define an objective metric to evaluate the results of
      different filter approaches, which verifies the results of the subjective survey.
      The proposed approach enables the automated reduction of fiberscopic comb
      structure. It is adaptive to arbitrary endoscope and sensor combinations. The
      results give the prospect of a large field of possible applications to reduce
      fiberscopic structure both for visual optimization in clinical environments and
      for further digital imaging tasks.

PMID- 17019869
TI  - Polarity effect in electrovibration for tactile display.
AB  - Electrovibration is the tactile sensation of an alternating potential between the
      human body and a smooth conducing surface when the skin slides over the surface
      and where the current is too small to stimulate sensory nerves directly. It has
      been proposed as a high-density tactile display method, for example to display
      pictographic information to persons who are blind. Previous models for the
      electrovibration transduction mechanism are based on a parallel-plate capacitor
      in which the electrostatic force is insensitive to polarity. We present
      experimental data showing that electrovibratory perceptual sensitivity to
      positive pulses is less than that for negative or biphasic pulses and propose
      that this disparity may be due to the asymmetric electrical properties of human
      skin. We furthermore propose using negative pulses for insulated tactile displays
      based on electrovibration because their sensory thresholds were found to be more
      stable than for waveforms incorporating positive pulses.

PMID- 17019870
TI  - Sensitivity- and effort-gain analysis: multilead ECG electrode array selection
      for activation time imaging.
AB  - Methods for noninvasive imaging of electric function of the heart might become
      clinical standard procedure the next years. Thus, the overall procedure has to
      meet clinical requirements as an easy and fast application. In this paper, we
      propose a new electrode array which improves the resolution of methods for
      activation time imaging considering clinical constraints such as easy to apply
      and compatibility with routine leads. For identifying the body-surface regions
      where the body surface potential (BSP) is most sensitive to changes in
      transmembrane potential (TMP), a virtual array method was used to compute local
      linear dependency (LLD) maps. The virtual array method computes a measure for the
      LLD in every point on the body surface. The most suitable number and position of
      the electrodes within the sensitive body surface regions was selected by
      constructing effort gain (EG) plots. Such a plot depicts the relative attainable
      rank of the leadfield matrix in relation to the increase in number of electrodes
      required to build the electrode array. The attainable rank itself was computed by
      a detector criterion. Such a criterion estimates the maximum number of source
      space eigenvectors not covered by noise when being mapped to the electrode space
      by the leadfield matrix and recorded by a detector. From the sensitivity maps, we
      found that the BSP is most sensitive to changes in TMP on the upper left frontal
      and dorsal body surface. These sensitive regions are covered best by an electrode
      array consisting of two L-shaped parts of approximately 30 cm x 30 cm and
      approximately 20 cm x 20 cm. The EG analysis revealed that the array meeting
      clinical requirements best and improving the resolution of activation time
      imaging consists of 125 electrodes with a regular horizontal and vertical spacing
      of 2-3 cm.

PMID- 17019871
TI  - Integrated optoelectronic probe including a vertical cavity surface emitting
      laser for laser Doppler perfusion monitoring.
AB  - An integrated optoelectronic probe with small dimensions, for direct-contact
      laser Doppler blood flow monitoring has been realized. A vertical cavity surface
      emitting laser (VCSEL), and a chip with photodetectors and all necessary
      electronics are integrated in a miniature probe head connected to a laptop
      computer. The computer sound processor is utilized for acquisition and digital
      signal processing of the incoming Doppler signal. In this paper, the design of
      the laser Doppler perfusion monitor is described and its performance is
      evaluated. We demonstrate our perfusion monitor to be less sensitive to subject
      motion than a commercial fiber-optic device. For medium and high perfusion
      levels, the performance of our integrated probe is comparable to the fiberoptic
      flowmeter containing a normal edge-emitting laser diode. For very low perfusion
      levels, the signal-to-noise ratio of the fiber-optic device is higher. This
      difference can mainly be attributed to the shorter coherence length of the VCSEL
      compared with the edge-emitting laser diode.

PMID- 17019872
TI  - Inductively heated shape memory polymer for the magnetic actuation of medical
      devices.
AB  - Presently, there is interest in making medical devices such as expandable stents
      and intravascular microactuators from shape memory polymer (SMP). One of the key
      challenges in realizing SMP medical devices is the implementation of a safe and
      effective method of thermally actuating various device geometries in vivo. A
      novel scheme of actuation by Curie-thermoregulated inductive heating is
      presented. Prototype medical devices made from SMP loaded with nickel zinc
      ferrite ferromagnetic particles were actuated in air by applying an alternating
      magnetic field to induce heating. Dynamic mechanical thermal analysis was
      performed on both the particle-loaded and neat SMP materials to assess the impact
      of the ferrite particles on the mechanical properties of the samples. Calorimetry
      was used to quantify the rate of heat generation as a function of particle size
      and volumetric loading of ferrite particles in the SMP. These tests demonstrated
      the feasibility of SMP actuation by inductive heating. Rapid and uniform heating
      was achieved in complex device geometries and particle loading up to 10% volume
      content did not interfere with the shape recovery of the SMP.

PMID- 17019873
TI  - A multitransducer microsystem for insect monitoring and control.
AB  - This paper reports the development and in-vivo testing of a compact
      multitransducer microsystem intended for neuroethology experiments, including
      studies of gait dynamics in free-running insects. The system incorporates a
      combination of custom and off-the-shelf components. Its suite of measurement
      devices comprises leg-mounted strain gauges, electromyogram (EMG) and
      extracellular electrodes for the central nervous system, and a two-axis
      accelerometer. For signal conditioning and selection, the microsystem implements
      off-the-shelf electronics in a custom chip-on-board configuration. The
      microsystem measures 16 mm x 19 mm, supports 40 components and 56 I/O leads, and
      is assembled on a four-layer printed-circuit board. The entire system occupies
      only 0.65 cm3 and weighs less than 5 g. It has been successfully used to monitor
      leg-strain and EMG signals on walking cockroaches and for stimulation in the
      insect central nervous and muscular systems.

PMID- 17019874
TI  - An implanted spherical head model exposed to electromagnetic fields at a mobile
      communication frequency.
AB  - Can cellular phones and personal communication systems base station antennas
      affect the active or passive implantable medical devices adversely? Concerns over
      the possible harmful effects of nonionizing irradiaton upon implanted medical
      devices have been present for many years. Key issues to address are the questions
      of whether mobile phones have a detrimental effect on implants, and how the
      interaction of the handset with the body can be minimized in order to both
      alleviate public fears and improve handset antenna performance and new implant
      designs. This paper presents a thorough investigation of the scattering of an
      electromagnetic (EM) wave from a perfectly conducting implant (a cylindrical wire
      and a very thin cylindrical disk) of electrically small radius (of resonant
      length), embedded eccentrically into a dielectric spherical head model by a
      dipole antenna (0.4 wavelength) at 900 MHz. The dyadic Green's function (DGF) for
      spherical vector wave functions is employed. Analytical expressions for the
      scattered fields of an implant embedded head model is obtained. Numerical results
      from analytical expressions are computed for this problem and then compared with
      the results from the same model using the finite-difference time-domain, EMU-FDTD
      electromagnetic simulator. Good agreement is observed between the analytical
      results on the proposed method in comparison with the FDTD method.

PMID- 17019875
TI  - Further documentation of remote effects of electrical injuries, with comments on
      the place of neuropsychological testing and functional scanning.
AB  - It is not always recognized that morbidity from electrical injury is not confined
      to effects in the pathway of current flow. Indeed a major element of the
      disability suffered by victims occur from effects remote to the line of current
      passage. Recent papers have rightly drawn further attention to this, and it is an
      active area of controversy and research. This paper documents the authors
      experience in this area and confirms the recognizable elements of remote injuries
      which are seen to be generally psychological in nature. The question of
      mechanisms of causation of these disabilities is raised. This paper then presents
      summary results of a collation of neuropsychological investigations and
      functional cerebral scanning in an attempt to correlate the two. It is concluded
      that it is possible to overlook the remote effects of electrical injury to the
      detriment of victims.

PMID- 17019876
TI  - A new decoupling method for quadrature coils in magnetic resonance imaging.
AB  - A powerful decoupling method is introduced to obtain decoupled signal voltages
      from quadrature coils in magnetic resonance imaging (MRI). The new method uses
      the knowledge of the position of the signal source in MRI, the active slice, to
      define a new mutual impedance which accurately quantifies the coupling voltages
      and enables them to be removed almost completely. Results show that by using the
      new decoupling method, the percentage errors in the decoupled voltages are of the
      order of 10(-7) % and isolations between two coils are more than 170 dB.

PMID- 17019877
TI  - Ultrasonic liver discrimination using 2-D phase congruency.
AB  - In this paper, we present an experiment to extract liver features using two
      dimensional phase congruency, which is invariant to changes in intensity or
      contrast, to try to avoid the influence of machine settings. The effectiveness of
      our method was tested on three classes of liver images and shows the potential
      for physicians to quantify liver pathology in clinical diagnosis.

PMID- 17019878
TI  - Predicting hepatitis C virus protease cleavage sites using generalized linear
      indicator regression models.
AB  - This paper discusses how to predict hepatitis C virus protease cleavage sites in
      proteins using generalized linear indicator regression models. The mutual
      information is used for model-size optimization. Two simulation strategies are
      adopted, i.e., building a model based on published peptides and building a model
      based on the published peptides plus newly collected sequences. It is found that
      the latter outperforms the former significantly. The simulation also shows that
      the generalized linear indicator regression model far outperforms the multilayer
      perceptron model.

PMID- 17019879
TI  - Underdetermined blind source separation of temporomandibular joint sounds.
AB  - The underdetermined blind source separation problem using a filtering approach is
      addressed. An extension of the FastICA algorithm is devised which exploits the
      disparity in the kurtoses of the underlying sources to estimate the mixing matrix
      and thereafter achieves source recovery by employing the ll-norm algorithm.
      Besides, we demonstrate how promising FastICA can be to extract the sources.
      Furthermore, we illustrate how this scenario is particularly appropriate for the
      separation of temporomandibular joint (TMJ) sounds.

PMID- 17019880
TI  - The rationale for studying transmitter interactions to understand the neural
      bases of cognitive function.

PMID- 17019881
TI  - Neurotransmitters and cognition.

PMID- 17019882
TI  - Interactions between CRF and acetylcholine in the modulation of cognitive
      behaviour.

PMID- 17019883
TI  - Forebrain dopaminergic-cholinergic interactions, attentional effort,
      psychostimulant addiction and schizophrenia.

PMID- 17019884
TI  - Intraseptal cholinergic infusions alter memory in the rat: method and mechanism.

PMID- 17019885
TI  - Modulation of visual perception and action by forebrain structures and their
      interactions in amphibians.

PMID- 17019886
TI  - Neuromodulators of LTP and NCAMs in the amygdala and hippocampus in response to
      stress.
AB  - Possibly, at the onset of an emotional event the stress hormones permissively
      mediate plasticity. Specifically, CORT and NE stress hormones participate in
      modulation of memory consolidation processes in both the amygdala and the
      hippocampus. In addition, glucocorticoids and norepinephrin bound to
      adrenoceptors are also involved in modulating the regulation of NCAM
      polysialylation both in the amygdala and in the hippocampus. PSA-related synaptic
      remodeling is mobilized for memory formation in particularly challenging
      circumstances.

PMID- 17019887
TI  - Central histaminergic system interactions and cognition.

PMID- 17019888
TI  - Cholinergic, histaminergic, and noradrenergic regulation of LTP stability and
      induction threshold: cognitive implications.

PMID- 17019889
TI  - Nicotinic-antipsychotic drug interactions and cognitive function.
AB  - In summary, neuronal nicotinic systems are important for a variety of aspects of
      cognitive function impacted by antipsychotic drugs. It has been demonstrated that
      antipsychotic drugs have memory and attentional impairing effects when given to
      unimpaired subjects. Nicotine can reduce some of these impairments, but
      antipsychotic drug administration can also attenuate nicotine effects. We have
      found that nicotinic agonists selective for alpha7 and alpha4beta2 receptor
      subtypes significantly improve learning and memory. Serotonergic actions of
      antipsychotic drugs may decrease efficacy of nicotinic co-treatments. When the
      antipsychotic drug clozapine and nicotine are administered to subjects with
      cognitive impairments caused by NMDA glutamate receptor blockade or hippocampal
      dysfunction they can significantly attenuate the attentional and memory
      impairments. Nicotine has been shown in our studies to reverse the memory
      impairment caused by acute clozapine-induced memory improvement. Acute
      risperidone and haloperidol has been shown to attenuate nicotine-induced memory
      improvement. We have determined the role of hippocampal alpha7 and alpha4beta2
      nicotinic receptors in the neural basis of nicotinic antipsychotic interactions.
      Local acute and chronic hippocampal infusion of either nicotinic alpha7 or
      alpha4beta2 antagonists cause significant spatial working memory impairment.
      Chronic hippocampal nicotinic antagonist infusions have served as a model of
      persistent decreases in nicotinic receptor level seen in schizophrenia and
      Alzheimer's disease. Clozapine attenuated the memory deficit caused by chronic
      suppression of hippocampal alpha4beta2 receptors while the amnestic effects of
      clozapine were potentiated by chronic suppression of hippocampal alpha7
      receptors. Nicotinic co-treatment may be a useful adjunct in the treatment of
      schizophrenia, to attenuate cognitive impairment of schizophrenia. Nicotine as
      well as selective nicotinic alpha7 and alpha4beta2 receptor agonists
      significantly improve working memory and attentional function. Nicotine treatment
      was found to be effective in attenuating the attentional and memory impairments
      caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of
      the cognitive impairment of schizophrenia. Studies of the interactions of
      antipsychotic drugs with nicotinic agents provided quite useful information
      concerning possible co-treatment of people with schizophrenia with nicotinic
      therapy. Nicotine was found to significantly attenuate the memory impairments
      caused by the antipsychotic drugs clozapine and olanzapine. Interestingly,
      nicotine-induced cognitive improvement was significantly attenuated by the
      antipsychotic drug clozapine. One of the principal effects of clozapine is to
      block 5HT2 receptors. Ketanserin a 5HT2 antagonist significantly attenuated
      nicotine-induced improvements in attention and memory. Thus it appears that
      antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy
      of nicotinic co-treatments for cognitive enhancement.

PMID- 17019890
TI  - Function and dysfunction of monoamine interactions in children and adolescents
      with AD/HD.

PMID- 17019891
TI  - Prepulse inhibition mechanisms and cognitive processes: a review and model.

PMID- 17019892
TI  - [Problems in applying a rapid assay kit for cardiac troponin T to medico-legal
      blood samples].
AB  - It is difficult to diagnose cardiac-related death only by external examination.
      However, in the areas where no medical examiner system is established, the
      diagnosis is made mostly from the findings by external examination. Clinically,
      cardiac troponin T (cTnT) rapid assay kits are used for the diagnosis of ischemic
      heart disease. The kits have started being applied to forensic medicine and used
      for the diagnosis of cardiac-related death without exact evidence. In this study,
      we collected postmortem blood samples from 110 forensic autopsy cases and
      evaluated the utility of the kits in the field of forensic medicine. Blood
      samples collected from the left and the right parts of the hearts showed
      extremely high positive rates (95.1% each), and peripheral blood samples also
      showed very high positive rates (71.2%), although cardiac-related deaths were
      only 7 cases of all 110 cases. Because cTnT concentration of postmortem blood
      samples is affected by non-cardiac-related natural death, postmortem changes, or
      cardiopulmonary resuscitation, the results from using the kits are not reliable
      in determining the cause of death. We conclude that the kits cannot be applied in
      forensic medicine.

PMID- 17019893
TI  - Topological factors in placental surface arteries correlate with neonatal birth
      weight.
AB  - OBJECTIVES: There has been no study concerning association between topological
      factors of placental vascularization and neonatal growth in humans. The aim of
      study was to assess whether any network index of placental surface arteries was
      associated with neonatal birth weight. MATERIALS AND METHODS: Twenty-six
      placentas were randomly selected between 34 and 41 weeks of gestational ages.
      Placental weights ranged 385 to 770 g; and neonatal weights ranged 1960 to 3680
      g. After visualization of placental surface arteries by a milk injection method,
      network indices including the number of nodes, network density, network diameter,
      average distance of nodes, and the degree centralization were determined. These
      network indices and placental weights were compared with neonatal birth weights.
      RESULTS: The number of nodes, network density, network diameter, average distance
      of nodes, and the degree centralization were found to be as follows (Mean +/-
      SD); 84.7 +/- 29.3, 0.0262 +/- 0.0088, 15.8 +/- 2.77, 7.83 +/- 1.13, 0.0263 +/-
      0.0091, respectively. We found that neonatal birth weights correlated with the
      number of nodes of placental surface arteries (correlation coefficient R = 0.40)
      and placental weights (R = 0.52) both. However, the number of nodes of placental
      surface arteries was not associated with the placental weights or the gestational
      age. CONCLUSIONS: We for the first time found that a topological factor, i.e.,
      the number of nodes of placental surface arteries correlated with neonatal
      growth. There was no correlation between numbers of nodes and placental weights.
      This suggests that the number of nodes affects fetal growth independent of
      placental weights. A topological factor of placental vascularization might
      significantly affect fetal growth in utero and determine risks of vascular
      diseases in their future lives.

PMID- 17019894
TI  - Small journal--but significant impact!

PMID- 17019895
TI  - Assessing expressed emotion: comparing Camberwell Family Interview and Five
      minute Speech Sample ratings for mothers of children with behaviour problems.
AB  - Little is known of the concordance between ratings of expressed emotion (EE)
      derived from the Camberwell Family Interview (CFI) and Five-minute Speech Sample
      (FMSS) for parents of children with behaviour problems. Concordance between CFI
      and FMSS ratings of EE was assessed prior to intervention and compared to parent
      rated behaviour after intervention, at follow-up, 12 months later. Female primary
      caretakers of 75 children (3-10 years) showing behavioural difficulties were
      interviewed using FMSS and CFI. Interviews were coded independently by criterion
      standard raters. Using CFI, 57 families were classified high EE, and 18 low EE.
      Using FMSS, 65 families were classified high EE and 10 low EE. 55/75 pairs of
      ratings (73%) were the same (high, n = 51: low, n = 4) and 20 mothers (27%) were
      allocated different EE status (Kappa = 0.14, n.s.). The FMSS ratings at initial
      interview appeared more closely related to behaviour rating at follow-up than
      CFI. Further investigation is required to establish comparability of CFI and FMSS
      results for carers of children.

PMID- 17019896
TI  - Evidence for a hallucinogen dependence syndrome developing soon after onset of
      hallucinogen use during adolescence.
AB  - This study uses latent class methods and multiple regression to shed light on
      hypothesized hallucinogen dependence syndromes experienced by young people who
      have recently initiated hallucinogen use. It explores possible variation in risk.
      The study sample, identified within public-use data files of the 1999 National
      Household Survey on Drug Abuse (NHSDA), consists of 1186 recent-onset
      hallucinogen users, defined as having initiated hallucinogen use within 24 months
      of assessment (median elapsed time since onset of use -12 to 13 months). The
      recent-onset users in this sample were age 12 to 21 at the time of assessment and
      were between the ages of 10 and 21 at the time of their first hallucinogen use.
      The NHSDA included items to assess seven clinical features often associated with
      hallucinogen dependence, which were used in latent class modelling. Latent class
      analysis, in conjunction with prior theory, supports a three-class solution, with
      2% of recent-onset users in a class that resembles a hallucinogen dependence
      syndrome, whereas 88% expressed few or no clinical features of dependence. The
      remaining 10% may reflect users who are at risk for dependence or in an early
      stage of dependence. Results from latent class regressions indicate that
      susceptibility to rapid transition from first hallucinogen use to onset of this
      hallucinogen dependence syndrome might be influenced by hallucinogenic compounds
      taken (for example, estimated relative risk, RR = 2.4, 95% CI = 1.6, 7.6 for
      users of MDMA versus users of LSD). Excess risk of rapid transition did not
      appear to depend upon age, sex, or race/ethnicity.

PMID- 17019897
TI  - Interrater reliability of the Psychiatric Research Interview for Substance and
      Mental Disorders in an HIV-infected cohort: experience of the National NeuroAIDS
      Tissue Consortium.
AB  - The interrater reliability of the Psychiatric Research Interview for Substance
      and Mental Disorders (PRISM) was assessed in a multicentre study. Four sites of
      the National NeuroAIDS Tissue Consortium performed blinded reratings of
      audiotaped PRISM interviews of 63 HIV-infected patients. Diagnostic modules for
      substance-use disorders and major depression were evaluated. Seventy-six per cent
      of the patient sample displayed one or more substance-use disorder diagnoses and
      54% had major depression. Kappa coefficients for lifetime histories of substance
      abuse or dependence (cocaine, opiates, alcohol, cannabis, sedative, stimulant,
      hallucinogen) and major depression ranged from 0.66 to 1.00. Overall the PRISM
      was reliable in assessing both past and current disorders except for current
      cannabis disorders when patients had concomitant cannabinoid prescriptions for
      medical therapy. The reliability of substance-induced depression was poor to fair
      although there was a low prevalence of this diagnosis in our group. We conclude
      that the PRISM yields reliable diagnoses in a multicentre study of substance
      experienced, HIV-infected individuals.

PMID- 17019898
TI  - Outcome revealed by preference in schizophrenia (OPS): development of a new class
      of outcome measurements.
AB  - The objective of this paper is to describe the development of a new type of
      outcome measurement, based on revealed preference, which can be used in serious
      chronic illnesses. Fifteen texts of about 200 words each were written by one of
      the authors on the day-to-day life of 15 schizophrenic patients. These 15 'slices
      of life' thus described were then ranked in terms of acceptability by a second
      group of 10 schizophrenic patients and by a group of 12 relatives of
      schizophrenic patients. From these rankings, six situations were selected so as
      to obtain evenly distributed positioning on an axis of acceptability. These six
      situations comprised the final instrument. In administration, the patients were
      first asked if the 'slices of life' that were described were acceptable or not,
      then if the 'slices of life' described were more or less acceptable than their
      own lives. Two scores were derived, one for an absolute level and the other for a
      relative level of the patient's satisfaction with his or her existence.
      Validation results were presented to a new sample of 229 schizophrenic patients.
      Internal consistency appeared good and the initial ranking of the six situations
      in terms of acceptability was confirmed. This study encourages the development of
      global outcome measures based on revealed preference in chronic serious
      illnesses.

PMID- 17019899
TI  - Model-based clustering using S-PLUS.
AB  - Cluster analysis can be used to identify homogenous subgroups in many fields,
      including psychology and psychiatry. However, most clustering methods implemented
      in general-purpose statistical packages are heuristic and can be criticized in
      principle for their lack of an underlying statistical model. Furthermore
      correlations between variables are generally ignored by standard methods. The
      question addressed here is whether currently available commercial software (S
      PLUS), which provides model-based methods for clustering correlated continuous
      data, should be used for clustering data derived from questionnaires. Such data
      may be either continuous or ordinal in nature and typically exhibit correlations.
      Performance is assessed in this study on simulated data sets containing distinct
      multivariate normal subpopulations, both before and after mapping the simulated
      data onto an ordinal scale. A practical example showing how correlated data can
      be cluster-analysed using these methods is given. The conclusion is that model
      based methods are certainly worthwhile for continuous data. However, their
      benefit, in particular their ability to deal with correlated data, is not marked
      for ordinal data. Simpler methods such as Ward's method may be almost as
      effective in this situation.

PMID- 17019900
TI  - Different results on tetrachorical correlations in Mplus and Stata--Stata
      announces modified procedure.
AB  - To identify the structure of mental disorders in large-scale epidemiological data
      sets, investigators frequently use tetrachoric correlations as a first step for
      subsequent application of latent class and factor analytic methods. It has been
      possible to do this with Stata since 2005, whereas the corresponding Mplus
      routine has been on the market for some years. Using an identical data set we
      observed considerable differences between the results of the packages. This paper
      illustrates the differences with several examples from the Early Developmental
      Stages of Psychopathology Study data set, which consists of 3021 subjects, with
      diagnostic information assessed by the CIDI. Results reveal that tetrachoric
      correlations resulting from Mplus were often considerably smaller than those
      computed with Stata. The results were dramatically different, especially where
      there were few observation per cell or even empty cells. These findings were put
      to Mplus and Stata, whose responses clarified the discrepancies by describing the
      different mathematical assumptions and procedures used. Stata announced that it
      intended to launch a modified procedure.

PMID- 17019901
TI  - Fine-tuning critical services maintenance.
AB  - Readers are recommended to make good use of the concepts of "Failure Model
      Effects and Criticality Analysis" as discussed above. These should provide a more
      comprehensive study of reliability and availability of building services. The
      assessment methodology presented in this article is to a certain extent
      subjective. It is considered that a more quantitative and comprehensive study
      based on reliability and availability data from similar hospitals over recent
      years will help the analysis. Building services maintenance involves risk. Risks
      must be assessed before a design is fully implemented. The risks associated with
      building services installation have to be assessed at all stages, from concept to
      dismantling and disposal. This will ensure that risks are acceptable and
      manageable within the parameters defined by the overall cost and engineering
      requirements, statutory obligations and good practice.

PMID- 17019902
TI  - Major issues still to be addressed.

PMID- 17019903
TI  - High definition images of surgery acclaimed.

PMID- 17019904
TI  - Facts extracted from dental surgeries.

PMID- 17019905
TI  - Historians and the healthcare of African Americans.

PMID- 17019906
TI  - Abraham Flexner and the black medical schools. 1992.
AB  - "Abraham Flexner and the Black Medical Schools" first appeared in Beyond Flexner:
      Medical Education in the Twentieth Century, Barbara Barzansky and Norman Gevitz,
      eds. Reproduced with permission of Greenwood Publishing Group Inc., Westport, CT.
      The article will be reprinted in a collection of the author's writings on African
      American medical history called Race and Medicine in Nineteenth- and Early
      Twentieth-Century America, to be published in December 2006 by Kent State
      University Press and published here with permission of the Kent State University
      Press.

PMID- 17019907
TI  - The forgotten history of defunct black medical schools in the 19th and 20th
      centuries and the impact of the Flexner Report.
AB  - There are currently four medical schools dedicated primarily to training African
      American physicians. Two of these schools were established in the last 40 years.
      For a generation prior to that, only Howard University College of Medicine and
      Meharry Medical College existed. Forgotten is the history of black medical
      schools established in the 19th and early 20th centuries, most of which are now
      defunct. While barriers to the medical education of African Americans in majority
      institutions have largely disappeared, the continued education of students at our
      four present-day black medical schools is again threatened. It is incumbent upon
      us not to allow these modern-day threats to destroy an important resource and
      legacy in the annals of African-American people. This paper explores medical
      education in the 19th and 20th centuries, the creation of black medical schools
      and the forces that lead to the demise of many of these institutions. In
      recalling this history, we acknowledge the almost-impossible odds faced by these
      pioneers and learn from their mistakes and failures.

PMID- 17019908
TI  - After Flexner: the challenge.
AB  - In his article, "Abraham Flexner and the Black Medical Schools," Todd Savitt, MD
      critically describes how the Flexner Report effectively decimated African
      American medical education as it existed at the beginning of the 20th century. We
      are now in the 21st century, and there are still few black physicians and medical
      students.

PMID- 17019909
TI  - Did Flexner's Report condemn black medical schools? Not so, in my opinion.
AB  - I invited Kathryn L. Moseley, MD to write the editorial appearing on the pages
      before this one as to whether she thought that the original Flexner Report was
      unduly harsh on the existing black medical schools. I invited her to choose
      whether she wanted to write the "pro" or "con" editorial, and that I would write
      the opposite piece for the sake of a presentation-although I might not
      necessarily believe in the position on which I was to write. She elected to write
      the "yes, it was harmful" piece, and I had to assume the editor's burden. In
      fact, as I began doing my internal soul searching for answers, I began to believe
      that the original Flexner Report actually helped preserve two black schools-
      Howard and Meharry--both of which might well have closed along with the other
      five schools scattered across the southeast, absent Flexner's direct and
      tangential support.

PMID- 17019910
TI  - Improving the retention of underrepresented minority faculty in academic
      medicine.
AB  - BACKGROUND: Although several studies have outlined the need for and benefits of
      diversity in academia, the number of underrepresented minority (URM) faculty in
      academic health centers remains low, and minority faculty are primarily
      concentrated at the rank of assistant professor. In order to increase the
      diversity of the faculty of the University of California, San Diego (UCSD) School
      of Medicine, the UCSD National Center for Leadership in Academic Medicine, in
      collaboration with the UCSD Hispanic Center of Excellence, implemented a junior
      faculty development program designed in part to overcome the differential
      disadvantage of minority faculty and to increase the academic success rate of all
      faculty. METHODS: Junior faculty received counseling in career and research
      objectives; assistance with academic file preparation, introduction to the
      institutional culture; workshops on pedagogy and grant writing; and instrumental,
      proactive mentoring by senior faculty. RESULTS: After implementation of the
      program, the retention rate of URM junior faculty in the school of medicine
      increased from 58% to 80% and retention in academic medicine increased from 75%
      to 90%. CONCLUSION: A junior faculty development program that integrates
      professional skill development and focused academic career advising with
      instrumental mentoring is associated with an increase in the retention of URM
      faculty in a school of medicine.

PMID- 17019911
TI  - In the minority: black physicians in residency and their experiences.
AB  - OBJECTIVE: To describe black residents' perceptions of the impact of race on
      medical training. MATERIALS AND METHODS: Open-ended interviews were conducted of
      black physicians in postgraduate year 22 who had graduated from U.S. medical
      schools and were enrolled in residency programs at one medical school. Using
      Grounded Theory tenets of qualitative research, data was culled for common themes
      through repeated readings; later, participants commented on themes from earlier
      interviews. RESULTS: Of 19 participants 10 were male, distributed evenly among
      medical and surgical fields. Four major themes emerged from the narratives:
      discrimination, differing expectations, social isolation and consequences.
      Participants' sense of being a highly visible minority permeated each theme.
      Overt discrimination was rare. Participants perceived blacks to be punished more
      harshly for the same transgression and expected to perform at lower levels than
      white counterparts. Participants' suspicion of racism as a motivation for
      individual and institutional behaviors was tempered by self-doubt. Social
      isolation from participants' white colleagues contrasted with connections
      experienced with black physicians, support staff and patients, and participants
      strongly desired black mentors. Consequences of these experiences varied greatly.
      CONCLUSIONS: Black physicians face complex social and emotional challenges during
      postgraduate training. Creating supportive networks and raising awareness of
      these issues may improve training experiences for black physicians.

PMID- 17019912
TI  - Mentoring for women and underrepresented minority faculty and students:
      experience at two institutions of higher education.
AB  - Women and minority faculty and students are seriously underrepresented in
      university and academic healthcare institutions. The role of mentoring has been
      identified as one of the significant factors in addressing this
      underrepresentation. We have described the mentoring efforts at two institutions
      of higher learning in assisting women and minority students and faculty in being
      accomplished in their academic pursuits. One-hundred-thirty students and >50
      women and minority faculty have participated in the mentoring programs described.
      The number of participants has increased dramatically over the years and
      continues to evolve positively. These programs appear to be quite successful in
      the short term. Further evaluation of measurable outcomes will be necessary to
      fully determine their true impact. The mentoring models for women and
      underrepresented minority faculty and students at Creighton University Health
      Sciences Schools and Wake Forest University School of Medicine will serve as a
      guide for other Health Sciences Schools.

PMID- 17019913
TI  - Impact of desire to work in underserved communities on selection of specialty
      among fourth-year medical students.
AB  - OBJECTIVE: The objective of this study was to explore the specific factors that
      influence medical student's choice of primary care as a specialty. Special
      attention is given to the influence of desire to work in underserved communities
      on selection of a specialty. DESIGN AND SETTINGS: A web-based survey of factors
      affecting choice of specialty was completed by 668 fourth-year students from 32
      medical schools. RESULTS: Students interested in primary care reported an
      increased likelihood of working with underserved populations when compared with
      other specialties. The independent impact of both student's social compassion
      attitudes and values, and subjective and reinforcing influences on the selection
      of primary care, when compared with all other specialties, was strong. Personal
      practice-oriented considerations showed an independent negative impact on the
      selection of primary care when compared with surgery and support specialties.
      Financial considerations strongly influence the selection of support specialties.
      Medical training experiences showed an independent influence on the selection of
      surgery over primary care. CONCLUSION: The need for primary care physicians and
      specialists in underserved communities is considerable. Addressing health
      disparities in underserved communities requires a concerted effort to increase
      the availability of primary care providers in these communities. This study
      observed that primary care practice or specialty selection by medical students is
      influenced by individual values and subjective external influences other than
      predicted by medical training alone. This observation necessitates a closer
      determination of strategies required to ensure an increase in the number of
      primary care physicians serving underserved communities.

PMID- 17019914
TI  - Proximal versus distal influences on underrepresented minority students pursuing
      health professional careers.
AB  - The Health Careers Opportunities Program (HCOP) at Creighton University provides
      an important illustration of the short- and long-term successes of pipeline
      programming. The Pipeline to Success program at Creighton University provides
      exposure and enrichment activities to participants beginning in middle school and
      continuing through a one-year postbaccalaureate component in order to ensure that
      they are knowledgeable about health professional careers and competitive in
      applying for these training programs. This study hypothesized that the enrichment
      activities experienced by participants would have the additional benefit of
      providing indirect or distal influences to motivate participants to meet their
      career goals. In partial support of this hypothesis, a MANOVA demonstrated that
      the middle-school participants demonstrated a different pattern of influence from
      the other program components. Results indicate that as participants progressed
      through the Pipeline to Success HCOP at Creighton University, the program
      resources impacted their desire to pursue health professional careers in addition
      to positively preparing them for health professional training programs. We
      conclude that these findings have particular importance for planning and
      implementing student education programs.

PMID- 17019915
TI  - Using resident focus groups to improve subspecialty consultations in a pediatric
      urgent care setting.
AB  - BACKGROUND: In a pediatric urgent care center, patients requiring management by
      subspecialty consultants have average waiting times of two hours. Pediatric
      resident input was sought in order to identify problems and propose urgently
      needed solutions. OBJECTIVES: 1) To define the dimensions on which residents
      measure quality of consultations; 2) To generate solutions for perceived
      problems. SETTING AND DESIGN: Mixed methods, including focus groups, survey
      questionnaires and an intervention, were used. Focus groups and questionnaires
      involved pediatric residents from a large public hospital that provides care to
      medically underserved African-American and Latino patients. RESULTS: Residents
      defined four dimensions of quality: waiting time, teaching, courtesy and overall
      quality of care. An intervention made with the service having the poorest ratings
      on the questionnaire consisted of a detailed discussion of focus group findings
      and recommendations. The overall effectiveness of the intervention was evaluated
      by analyzing pre- and postprogram measures. Postintervention ratings showed
      significant improvement of ratings along three of the four dimensions of concern.
      CONCLUSIONS: At minimal-to-no cost to an institution, focus groups composed of
      residents can generate viable solutions to observed problems. This form of
      feedback could be beneficially incorporated into an institution's continuous
      quality improvement processes.

PMID- 17019916
TI  - Obesity prevention in pediatrics: A pilot pediatric resident curriculum
      intervention on nutrition and obesity education and counseling.
AB  - INTRODUCTION: Obesity is a highly burdensome public health issue associated with
      premature death, multiple comorbid disabilities and staggering healthcare costs.
      Between 1980-2000, the prevalence of obesity among children and adolescents
      nearly tripled. Obesity subjects youth to social stigmatization and
      discrimination. These economic and personal burdens mandate targeted prevention
      and detection educational programs for all individuals at risk. The most cost
      effective method of approaching this obesity epidemic is through education of
      health professionals. METHODS: As part of an "Obesity Prevention in Pediatrics"
      curriculum, postgraduate-year (PGY)-2 residents first observed and then
      participated in the dietary evaluation and counseling of pediatric patients and
      their families. Attitudinal questionnaires, multiple-choice knowledge
      examinations and a pre-established checklist of desired skills and behaviors
      provided evaluation of the curriculum's effect on the participants' ability and
      willingness to manage actually obese or at-risk pediatric patients and their
      families. RESULTS: Attitudinal survey and knowledge test scores from control PGY
      3 residents generally confirmed that their knowledge and counseling skills on
      obesity prevention and management were well below expectation. Following
      participation in the curriculum, study residents' knowledge tended to improve, as
      did their level of comfort in counseling obese and at-risk children, adolescents
      and their parents. CONCLUSION: Implementation of an "Obesity Prevention in
      Pediatrics" curriculum appears to improve participants' knowledge base as well as
      their skills and level of personal comfort in the recognition, evaluation and
      management, including counseling, of both obese and at-risk pediatric patients
      and their families.

PMID- 17019918
TI  - Reconsideration of the training of psychiatrists and mental health professionals:
      helping to make soup.
AB  - For many years, we have known of deficits in our system of training mental health
      professionals, particularly in recognizing and integrating diversity. Recently,
      we have begun to understand that our literature must more authentically reflect
      the experiences of all people that we serve. The current paper suggests that a
      comprehensive biopsychosocial conceptualization of normal and abnormal behavior
      for all individuals is necessary to truly begin to reduce mental health
      disparities. The authors argue that factors such as racial, ethnic and cultural
      differences must be integrated into research before the literature will begin to
      change in a fashion that is beneficial to the mental health training process.

PMID- 17019917
TI  - Pediatric residency training on tobacco: review and critique of the literature.
AB  - OBJECTIVE: To review and critique the research literature on training pediatric
      residents to address tobacco. METHODS: A Medline search was conducted to identify
      studies that specifically addressed pediatric residency training on tobacco, and
      Google Scholar was used to identify articles in which the referenced study was
      cited. RESULTS: Eight studies that specifically addressed training pediatric
      residents to intervene on tobacco were identified. Most used active as well as
      passive approaches to training. Baseline data underscored the importance of
      training future pediatricians to address tobacco. Although the studies differed
      in size, scope and rigor, they showed that training pediatric residents to
      address tobacco enhanced residents' ability and likelihood to address tobacco.
      CONCLUSION: The review documents the importance and value of training pediatric
      residents to address tobacco, provides suggestions for future research and
      underscores the need to incorporate training on tobacco into pediatric residency
      training curriculum.

PMID- 17019919
TI  - Hospitalists in medical education: coming to an academic medical center near you.
AB  - Hospitalists are physicians whose medical practice focuses on general medical
      inpatient care. In the past decade, the number of practicing hospitalists has
      soared, and hospitalist programs have been established at both community
      hospitals and academic medical centers. As hospitalists increasingly assume a
      greater share of inpatient care responsibilities, they will contribute to the
      training of medical students and house staff. This paper reviews current data on
      the impact of hospitalists on medical education and the future of hospitalist
      training.

PMID- 17019920
TI  - Development of a replicable process for translating science into practical health
      education messages.
AB  - There has been considerable discussion about translating science into practical
      messages, especially among urban minority and "hard-to-reach" populations.
      Unfortunately, many research findings rarely make it back in useful format to the
      general public. Few innovative techniques have been established that provide
      researchers with a systematic process for developing health awareness and
      prevention messages for priority populations. The purpose of this paper is to
      describe the early development and experience of a unique community-based
      participatory process used to develop health promotion messages for a
      predominantly low-income, black and African-American community in Baltimore, MD.
      Scientific research findings from peer-reviewed literature were identified by
      academic researchers. Researchers then taught the science to graphic design
      students and faculty. The graphic design students and faculty then worked with
      both community residents and researchers to transform this information into
      evidence-based public health education messages. The final products were
      culturally and educationally appropriate, health promotion messages reflecting
      urban imagery that were eagerly desired by the community. This early outcome is
      in contrast to many previously developed messages and materials created through
      processes with limited community involvement and by individuals with limited
      practical knowledge of local community culture or expertise in marketing or mass
      communication. This process may potentially be utilized as a community-based
      participatory approach to enhance the translation of scientific research into
      desirable and appropriate health education messages.

PMID- 17019922
TI  - The bridge to diversity: the role of the National Medical Association and the
      African-American physician.
AB  - Three major reports confirming the presence of health disparities have made
      significant recommendations toward their elimination. One of the major
      recommendations is to increase the number of African-American and minority
      physicians. These recommendations come at a time when some communities are
      experiencing a physician shortage and some are forecasting a nationwide physician
      shortage. The National Medical Association and members of the African-American
      and minority physician community are in the best position to bring the necessary
      parties together to address this issue on local and national levels. Are we ready
      to respond to the call to action?

PMID- 17019921
TI  - Caregiver intervention research: an opportunity for collaboration between
      caregiving investigators and African-american faith communities.
AB  - The African-American community in the United States is rapidly aging. Because
      friends and family who care for these elderly individuals often do so at the
      expense of their own physical and psychological well-being, there has been
      extensive interest in the development of interventions to reduce caregiver burden
      and morbidity. Few interventions, however, have targeted African-American
      caregivers. Given the importance of religion for many African-American
      caregivers, we believe that faith communities could be valuable allies to
      research investigators. The primary objectives of this paper, therefore, are to:
      1) summarize the literature on religion and African-American caregivers; 2)
      provide a rationale for why caregiving investigators and African-American faith
      communities should collaborate; and 3) present directions for future research. We
      present evidence to support our assertion that, not only could collaboration
      result in interventions that improve the well-being of African-American
      caregivers, collaboration would also benefit both caregiving investigators and
      faith communities.

PMID- 17019923
TI  - Influence of medical education on students' attitudes towards the elderly.
AB  - As life expectancy increases, the elderly population grows accordingly. Today,
      physicians interface with elderly patients more frequently and, therefore,
      geriatric education should be a part of medical training. Examining medical
      students' knowledge and attitudes about elderly will provide valuable information
      in planning the geriatric education in medical school. The aim of this study is
      to determine and compare the attitudes and knowledge of class-1, -4 and -6
      Turkish medical students about the elderly. A questionnaire that included
      statements about physical and social situations of the elderly, developed by
      Reuben et al., was used. Five-hundred-thirty-five students educating in Hacettepe
      University Medical Faculty took part in the study. Age, gender and the number of
      people aged >65 living with the students were also asked. Gender and number of
      old people living with the students had no significant effect on the answers.
      Social statements were answered positively, and there were no significant changes
      among the classes. Statements about physical situations and illnesses were
      significantly associated with the students' years of education. Geriatric
      education in developing countries needs more attention because the students'
      attitudes towards elderly and caregiver preference are mostly affected by the
      students' own experiences and knowledge.

PMID- 17019924
TI  - Experiences promoting healthcare career interest among high-school students from
      underserved communities.
AB  - Promoting early interest in healthcare careers among youth from underserved areas
      is one promising strategy for addressing the health professional shortage in such
      communities, Most career choice studies try to predict outcomes using such
      traditional measures as grades and test scores, This study examines experiences
      influencing healthcare career interest among high-school students participating
      in health professions introductory programs in underserved communities. The
      opinions of parents and teachers regarding students' motivations are also
      considered. Seven focus groups (N=51) were conducted in one rural and two largely
      minority urban communities in New York State designated as health professional
      shortage areas. Qualitative data analysis involved a theory-driven, immersion and
      crystallization approach following the experiential learning model. Constructive
      experiences with the healthcare system, family role-modeling and support,
      interactive health-related school activities, the media, inspirational and
      accessible school staff, and strategic community partnerships, among other
      factors, facilitated student interest in health professions. Findings suggest
      that underserved and disenfranchised community environments still pose challenges
      for furthering healthcare career interest among youth.

PMID- 17019925
TI  - Effects of perceived racism, cultural mistrust and trust in providers on
      satisfaction with care.
AB  - Discriminatory treatment of African Americans in healthcare is well recognized,
      yet the literature is unclear on the specific role that perceived racism and
      mistrust play in the patient-provider relationship. The purpose of this study was
      to test a mid-range theoretical model entitled Perceptions of Racism and Mistrust
      in Health Care (PRMHC). This model hypothesized that perceived racism influences
      cultural mistrust, which affects trust in providers--and these combined
      psychosocial aspects of healthcare affect satisfaction with the care received.
      One-hundred-forty-five African-American subjects participated in structured
      interviews to collect demographic and psychosocial data. Provider data was
      obtained through chart audits. In a group of low-income African Americans in two
      primary care clinics, perceptions of racism and mistrust of whites had a
      significant negative effect on trust and satisfaction. Perceived racism had both
      a significant, inverse direct effect on satisfaction as well as a significant
      indirect effect on satisfaction mediated by cultural mistrust and trust in
      provider. Structural equation modeling analysis supported the hypothesized
      theoretical relationships and explained 27% of the variance in satisfaction with
      care. The findings add to the existing literature by enhancing our understanding
      of the complex perspectives on trust and overall satisfaction with care among
      African-American patients. Results suggest that improving health outcomes for
      African Americans requires a broader understanding of cultural competence, one
      that addresses societal racism and its impact on provider-patient relationships.

PMID- 17019926
TI  - Mentoring women in academic surgery: overcoming institutional barriers to
      success.
AB  - Women now comprise 50% of Caucasian matriculants to medical school; 66.6% of
      African Americans, 48% of Hispanics and 51.3% of Asians beginning medical school
      are also women. This trend is likely to continue since women now earn 57% of all
      undergraduate degrees, and they earn more degrees in the health professions and
      biological sciences than men. Black and Hispanic women now earn 66% and 60% of
      bachelor's degrees in their respective ethnic groups. Overall, women are
      concentrated at the lowest faculty ranks at medical schools, with 70% holding the
      rank of instructor or assistant professor. Women continue to experience
      difficulty with recruitment, retention, promotion and pay issues compared to men.
      They also experience additional gender-specific issues, including primary
      responsibility for rearing families and quality-of-life issues in some
      specialties, including most of the surgical disciplines. Clearly, there is an
      evolving population shift at work here; the pool of candidates for medical school
      faculty positions is likely to be evenly split between men and women for
      Caucasians, Hispanics and Asians, while the African-American pool is likely
      heavily weighted in favor of the women. Women are beginning to garner more Latin
      honors recognition at graduation as well and the definition of the "best and the
      brightest" is being redefined. Therefore, institutions must continue to identify
      the barriers that deter women from entering surgery, to develop research tools to
      understand how to improve the process of developing leadership skills among women
      and to insure a "buy-in" of their male counterparts when components of the plan
      are being implemented.

PMID- 17019927
TI  - Rights, Bunche, Rose and the "pipeline".
AB  - We address education "pipelines" and their social ecology, drawing on the 1930's
      writing of Ralph J. Bunche, a Nobel peace maker whose war against systematic
      second-class education for the poor, minority and nonminority alike is nearly
      forgotten; and of the epidemiologist Geoffrey Rose, whose 1985 paper spotlighted
      the difficulty of shifting health status and risks in a "sick society. From the
      perspective of human rights and human development, we offer suggestions toward
      the paired "ends" of the pipeline: equality of opportunity for individuals, and
      equality of health for populations. We offer a national "to do" list to improve
      pipeline flow and then reconsider the merits of the "pipeline" metaphor, which
      neither matches the reality of lived education pathways nor supports notions of
      human rights, freedoms and capabilities, but rather reflects a commoditizing
      stance to free persons.

PMID- 17019928
TI  - HPLC-MS trace analysis of atropine in Lycium barbarum berries.
AB  - The dried ripe fruits of Barbary wolfberry, Lycium barbarum L. are widely used in
      China for medicinal purposes and as a functional food. Previous investigations
      reported to have found atropine in Barbary wolfberries from India. These results
      have been questioned. Since then, however, there has been a discussion on whether
      the berries are suitable for human consumption. In order to determine the content
      of atropine, we have analysed eight samples of berries from China and Thailand
      for traces of atropine, using highly selective and sensitive HPLC-MS methods.
      Atropine was found in all examined samples in concentrations of maximally 19 ppb
      (w/w). Therefore, the content is far below toxic levels.

PMID- 17019929
TI  - A high-throughput monolithic HPLC method for rapid vitamin C phenotyping of berry
      fruit.
AB  - A rapid method for the quantification of L-ascorbic acid (1) in berry fruit by
      HPLC with photodiode array detection is presented. L-Ascorbic acid was resolved
      on a C18 monolithic column with aqueous buffer, after which the column was washed
      with acetonitrile to remove lipophilic compounds prior to re-equilibration for
      analysis of the next sample. Using the monolithic column format with high mobile
      phase flow rates, the entire separation, wash and re-equilibration were achieved
      in 3 min. With the exception of gooseberry (Ribes uva-crispa), for which an
      interfering compound co-eluted, concentrations of 1 could be determined in a wide
      range of berry fruits after extraction in metaphosphoric acid without further
      sample preparation. Using this extraction method, recoveries of 1 in excess of
      85% were achieved. Fruit or juice extracts were stable in 5% metaphosphoric acid
      for at least 4 h and stability could be extended to longer than 150 h by the
      addition of the reducing agent tris(2-carboxethyl)phosphine hydrochloride.
      Following validation, the method was utilised for the phenotyping of fruit in a
      Scottish Crop Research Institute (SCRI) Ribes nigrum L. breeding population of
      300 individuals. An improved extraction method allowed extraction, quantification
      of 1 and data analysis to be undertaken in less than one working week.

PMID- 17019930
TI  - Development of an HPLC-PAD-MS assay for the identification and quantification of
      major phenolic edelweiss (Leontopodium alpium Cass.) constituents.
AB  - The analytical assessment of edelweiss (Leontopodium alpinum) herb extracts, used
      in traditional alpine medicine, has resulted in the development of a HPLC-PAD-MS
      method that allows baseline separation of almost all constituents. Peak
      assignment of 14 analytes was achieved by comparison of retention times, UV and
      mass spectra with those of reference compounds either commercially available
      (luteolin, apigenin and chlorogenic acid) or isolated from edelweiss plants by
      column chromatography. Ten of the isolated analytes were identified as the known
      natural products: quercetin-3-O-beta-D-glucoside, luteolin-7-O-beta-D-glucoside,
      luteolin-3'-O-beta-D-glucoside, luteolin-4'-O-beta-D-glucoside, apigenin-7-O-beta
      D-glucoside, 6-hydroxy-luteolin-7-O-beta-D-glucoside, luteolin-7,4'-di-O-beta-D
      glucoside, chrysoeriol-7-O-beta-D-glucoside, leontopodic acid and 3,5
      dicaffeolyquinic acid. One analyte, 3,4,5-tri-(E)-caffeoly-D-glucaric acid proved
      to be a new natural product and was named leontopodic acid B. Structure
      elucidation was carried out by means of MS and NMR spectroscopy in all cases. The
      aerial plant parts of L. alpinum (capitula, inflorescence leaves, stems, stem
      leaves and leaves of the basal rosette) showed variable amounts of the above
      mentioned constituents, although qualitative differences were not observable.

PMID- 17019931
TI  - A combined HPLC-UV and HPLC-MS method for the identification of lignans and its
      application to the lignans of Linum usitatissimum L. and L. bienne Mill.
AB  - A combined HPLC-UV/PAD and HPLC-ESI/MS method allowing the fast detection and
      identification/structural characterisation of lignans of different structural
      subclasses is described. Twenty-four lignans of different skeletal types were
      analysed and the combined information derived from their UV and ESI/MS spectra
      led to the identification of group characteristics that can be used to establish
      the structure of unknown lignans in plant samples. This method was successfully
      applied to the identification of lignans in crude extracts of Linum usitatissimum
      L. and L. bienne Mill.

PMID- 17019932
TI  - Prenylated stilbenes from peanut root mucilage.
AB  - Seven prenylated stilbenes were identified by combined HPLC-PAD-APCI/MSn analysis
      of an extract of mucilage isolated from peanut (Arachis hypogaea L.) root tips.
      The principal constituent was assigned the structure 4-(3-methyl-but-1-enyl)-3, 5
      dimethoxy-4'-hydroxy-trans-stilbene. The common name mucilagin A is proposed for
      this novel compound. Its concentration in the mucilage was estimated at 250
      microg/g (wet weight basis). The large body of literature on the anti-microbial
      properties of plant-derived stilbenes suggests that compounds detected in peanut
      mucilage may play a role in regulating root-soil pathogen interactions.

PMID- 17019933
TI  - Application of principal components analysis to 1H-NMR data obtained from
      propolis samples of different geographical origin.
AB  - Propolis is a widely used natural remedy and a range of biological activities
      have been attributed to it. The chemical composition of propolis is highly
      variable and its quality is often controlled on the basis of one or two marker
      compounds. In order to progress towards a method for the quality control of this
      complex material, HPLC and 1H-NMR approaches as methods of quality control have
      been compared. HPLC analyses of 43 samples of propolis were carried out and six
      marker compounds were quantified in each sample. The same samples were analysed
      using 1H-NMR and the spectra were then converted into their first derivative
      forms and digitised using the software application MestRe-C. The digitised data
      were subjected to principal component analysis using the software application
      Simca-P. It was found that the chemical composition of propolis mapped well
      according to the geographical origins of the samples studied when the first three
      principal components were used to display them. In addition, each sample was
      assessed for anti-oxidant activity, and the results were then overlaid onto the
      sample groupings according to 1H-NMR data. It was observed that anti-oxidant
      properties also mapped quite well according to geographical origin.

PMID- 17019934
TI  - The determination of huperzine A in European Lycopodiaceae species by HPLC-UV-MS.
AB  - A rapid qualitative HPLC-UV-MS method was developed for the detection of
      huperzine A in Lycopodiaceae species. HPLC coupled with mass spectrometry
      experiments allowed the identification of the alkaloid and enabled targeted
      analysis of complex matrices such as herbal extracts. Huperzine A was detected by
      single ion monitoring of the pseudomolecular ion [M + H]+ at m/z 243.2. The
      alkaloid was also detected on TLC in a bioautographic enzyme assay with
      acetylcholinesterase to show the activity of the compound. Four Lycopodiaceae
      species collected in Switzerland were tested by these methods and Huperzia selago
      (L.) Bernh. ex Schrank et Martius was the only species found to contain huperzine
      A.

PMID- 17019935
TI  - On-line identification of further flavone C- and O-glycosides from sugarcane
      (Saccharum officinarum L., Gramineae) by HPLC-UV-MS.
AB  - HPLC-UV-MS (APCI-MS/MS and CID/MS) was utilised for the identification of eight
      additional flavone glycosides from sugarcane (Saccharum officinarum L.,
      Gramineae) extracts of bagasse, leaves and juice ('garapa'). Relevant information
      about substitution patterns was obtained through UV detection using post-column
      addition of shift reagents, while tandem MS provided structural information
      confirming the proposed structures of the C-glycosides vitexin, orientin,
      luteolin-8-C-(rhamnosylglucoside), 4',5'-dimethyl-luteolin-8-C-glycoside and the
      isomeric pair schaftoside-isoschaftoside, besides the O-glycosides tricin-7-O
      neohesperidoside and tricin-7-O-glycoside.

PMID- 17019936
TI  - Phenols and lignans from Chenopodium album.
AB  - Cinnamic acid, 4-hydroxy-cinnamic acid, ferulic acid, methyl ferulate, sinapic
      acid, methyl 3-(4-hydroxy-3-methoxyphenyl)propanoate, 4-(1-hydroxyethyl)-2
      methoxyphenol, vanillyl alcohol, 4-(hydroxymethyl)-2-methoxyphenol, 4-hydroxy-3
      methoxybenzoic acid, 4-vinylphenol, 4-methylbenzaldehyde, N-[2-(1H-indol-3
      yl)ethyl]acetamide, pinoresinol, syringaresinol, lariciresinol, 5,5'-dimethoxy
      lariciresinol, threo-guaiacylglycerol-3-beta-4-syringaresinol ether and two new
      sesquilignans, namely, threo-guaiacylglycerol-alpha-O-methyl-beta-O-4
      syringaresinol ether and threo-syringylglycerol-alpha-O-methyl-beta-O-4
      syringaresinol ether, were isolated and identified as components of Chenopodium
      album. Constitutions were established on the basis of spectroscopic data,
      including two-dimensional NMR analyses.

PMID- 17019937
TI  - Purification and characterization of an N-acetyl-D-galactosamine-specific lectin
      from seeds of chickpea (Cicer arietinum L.).
AB  - A novel lectin (CAA-II) was isolated and purified from the seeds of Cicer
      arietinum by ammonium sulphate fractionation and affinity chromatography on an N
      acetyl-D-galactosamine-linked agarose column. The lectin is composed of four
      identical subunits of 30 kDa and the molecular mass of the native lectin was
      estimated to be 120 kDa by gel filtration chromatography and confirmed by mass
      spectrometry. The lectin showed agglutination activity against rabbit
      erythrocytes (trypsin-treated and untreated) as well as against human
      erythrocytes. Haemagglutination inhibition assays showed that the lectin is a
      galactose-specific protein having a high affinity for N-acetyl-D-galactosamine.
      The molecular weight, haemagglutination pattern, carbohydrate specificity and N
      terminal amino acid sequence indicated that the lectin is clearly distinct from
      the previously reported chickpea lectin CAA-I.

PMID- 17019938
TI  - Relation between in vitro production of ascosonchine and virulence of strains of
      the potential mycoherbicide Ascochyta sonchi: a method for its quantification in
      complex samples.
AB  - The potential of the fungus Ascochyta sonchi as a mycoherbicide for the
      biocontrol of the perennial weeds Sonchus arvensis and Cirsium arvense that occur
      throughout temperate regions of the world is under evaluation. Ascosonchine, a
      newly discovered enol tautomer of 4-pyridylpyruvic acid with potential herbicidal
      properties, is the main phytotoxin produced by this fungus. A simple and
      sensitive method has been developed for the rapid quantitative analysis of
      ascosonchine based on HPLC with UV detection. The toxin content in culture
      filtrates of different strains of A. sonchi was measured. The strains tested
      produced up to 2.7 mg/L when grown in static conditions. Toxin production was
      compared with the virulence on the host plant of each strain to determine if the
      most virulent strains could be simply selected by choosing the best toxin
      producers. The results obtained do not support this approach. The same HPLC
      method was also applied to quantify toxin production under different fungal
      growth conditions, in order to achieve the highest toxin production. The most
      productive strain synthesised more than 8 mg/L when grown for 8 weeks in static
      conditions.

PMID- 17019939
TI  - HPLC quantification of alkaloids from Haplophyllum extracts and comparison with
      their cytotoxic properties.
AB  - An efficient system for the analysis of total alkaloids extracted from the aerial
      parts from different species of genus Haplophyllum (Rutaceae) by HPLC on a
      reversed-phase column is described. The HPLC method described was validated for
      its specificity, linearity and precision using external standards (haplopine,
      skimmianine and haplamine). The chromatographic conditions allowed the separation
      of alkaloids and the quantification of haplopine, skimmianine and haplamine in
      different samples of species of Haplophyllum collected in Uzbekistan. The
      alkaloidal contents of samples were compared with their in vitro cytotoxic
      properties against two cancer cell lines (HeLa and HCT-116). The cytotoxicity of
      extracts was correlated with the concentration of haplopine, skimmianine or
      haplamine in aerial parts of species of Haplophyllum.

PMID- 17019940
TI  - Current awareness in phytochemical analysis.

PMID- 17019941
TI  - Physiotherapy: the ultimate placebo.

PMID- 17019942
TI  - Development pathways in learning to be a physiotherapist.
AB  - BACKGROUND AND PURPOSE: Few studies have examined the experiences of students'
      professional socialization in physiotherapy. This international longitudinal
      study aimed to study experiences of situated learning and change in a student
      cohort during a physiotherapy education programme. METHOD: A phenomenographic
      design with semi-structured interviews was carried out with a cohort of
      physiotherapy students from two sites, strategically selected for variation in
      gender, age, educational background, work experience and academic level.
      Interviews were carried out after each of the first five semesters in the
      programme by a team of researchers. Seventy-six interviews explored students'
      learning experiences. Analysis identified the variation in experiences seen as
      important to becoming a physiotherapist. RESULTS: Distinct perceptions of
      professional growth and progression are identified in four pathways of
      development: 'Reflecting on Practice'; 'Communicating with Others'; 'Performing
      Skills'; and 'Searching Evidence'. These pathways demonstrate qualitative
      differences in the focus of learning experiences and preferred learning context,
      and include learning in a context which supports reflection, learning as agreed
      by others in a context with patients and other professionals, learning
      physiotherapy skills in a practice context and learning formal knowledge in a
      context where theory can be linked with practice. CONCLUSIONS: In a cohort of
      students professional growth can be seen in a variety of development pathways.
      Each shows progress of professional growth in the 'what' as changes in
      experiences and the 'how' as ways of learning from them. In addition, the pattern
      of pathways in a cohort may change from one semester to another suggesting
      individuals may adopt different learning pathways throughout their education.
      Teaching staff are challenged to consider how they recognize a variation in
      development pathways in their student cohorts and how they purposefully ensure
      experiences to guide students through different learning pathways in
      socialization to become a physiotherapist.

PMID- 17019943
TI  - Movement-based feedback may reduce spinal moments in male workers during lift and
      lowering tasks.
AB  - BACKGROUND AND PURPOSE: To assess if lifting performance can be modified and
      spine stresses reduced in workers who perform repetitive material-handling jobs
      in a warehouse environment via a novel real-time, movement-based feedback
      training protocol. METHOD: A pre-test/post-test group study design was used with
      a control group. Data were collected in a warehouse setting and analysed in a
      university setting. A convenience sample of 22 male warehouse employees was
      divided equally, based on height and weight, and assigned to either an
      experimental group or a control group. The experimental group received real-time,
      performance-based auditory feedback from their calculated moments during lifting
      or lowering using an electromagnetic tracking system. The electromagnetic
      tracking system was used to measure the side-bending, flexion and rotation
      moments during six lifts under four different conditions. A series of repeated
      measures analyses of variance (ANOVA) (one between (Group); one within (Time))
      was performed on the average maximum moments from six lifting or lowering cycles
      for all three directions: side-bending, flexion and rotation. RESULTS: There were
      significant group x time interactions for the side-bending moment (p < 0.05) and
      the flexion moment (p < 0.05) but not the rotation moment (p > 0.05). Lower
      moments were found in the experimental group, which received the training and
      feedback, compared to the control group. CONCLUSIONS: Real-time, auditory
      feedback combined with coaching during lifting or lowering tasks may be effective
      in the short term (six weeks) in reducing the average maximum side-bending and
      flexion moments in warehouse workers. Further research is needed to determine the
      long-term effects of this training protocol on low back injury rates.

PMID- 17019944
TI  - An investigation into EMG activity in the upper and lower portions of the
      subscapularis muscle during normal shoulder motion.
AB  - BACKGROUND AND PURPOSE: The subscapularis (SSc) muscle is considered to perform a
      variety of roles during normal shoulder movement. The SSc is innervated by two or
      more discrete motor nerves and previous studies have indicated some difference in
      electromyographic (EMG) activity between the upper and lower portions of the
      muscle. The purpose of the present study was to compare EMG activity between the
      upper and lower portions of the SSc muscle during voluntary shoulder movements in
      normal healthy subjects. METHOD: Eight subjects were evaluated. A pair of
      intramuscular electrodes was inserted into each portion of the muscle. EMG data
      were recorded during the following movements: sagittal flexion; abduction in the
      coronal plane; and abduction in the scapular plane. RESULTS: EMG onset of the
      upper portion of subscapularis occurred significantly earlier compared to the
      lower portion. Differences were also seen in the level and pattern of activation
      between the two portions, with upper SSc demonstrating higher levels of
      activation than the lower portion. CONCLUSIONS: These findings suggest that the
      upper and lower portions of SSc are differentially active during voluntary
      shoulder movements.

PMID- 17019945
TI  - Lidocaine iontophoresis mediates analgesia in lateral epicondylalgia treatment.
AB  - BACKGROUND AND PURPOSE: Iontophoresis transcutaneously delivers anti-inflammatory
      and analgesic drugs for the treatment of musculoskeletal dysfunction. Lidocaine
      is a local anaesthetic with analgesic but no anti-inflammatory properties. The
      purpose of this investigation was to examine the clinical use of lidocaine
      iontophoresis-mediated analgesia in a larger treatment algorithm for five
      patients with lateral humeral epicondylalgia. METHOD: The investigation was a
      case series design of five subjects, aged 52 (+/- 6) years, with epicondylalgia
      of 12-393 days' duration. At each treatment session, the patients received
      cryotherapy, cross-fibre massage and passive stretch. Between sessions analgesia
      was provided by an 80 mA-min low-current, long-duration lidocaine iontophoresis
      (LI) over a 24-hour period. Patients were treated on an every-other-day basis for
      a total of three treatment sessions. Clinical improvements were determined by
      triplicate measurements of dolorimetric force over the affected epicondyle prior
      to treatment 1 (baseline), prior to sessions 2 and 3, and one week following the
      last session. RESULTS: Patients demonstrated an increasing tolerance to
      dolorimetric force application prior to the next session. The force values prior
      to session 2 (3.1 (+/- 1.1) Newton (N)) and one week following the third session
      (3.4 (+/- 0.5) N) were significantly improved from the baseline values (2.1 (+/-
      0.9) N). CONCLUSIONS: Pain associated with lateral epicondylalgia decreased, and
      function improved in all patients at the final measurement. One patient returned
      during the 90-day follow-up period to seek additional medical attention. This
      investigation documents the potential for analgesia provided by LI in the
      rehabilitation process of musculoskeletal dysfunction.

PMID- 17019946
TI  - Longitudinal investigation of low back pain in Australian adolescents: a five
      year study.
AB  - BACKGROUND AND PURPOSE: Adolescent spinal pain is a worldwide concern, with few
      longitudinal studies to validate concerns that an increasing number of
      adolescents report pain with age. The aim of the present study was to track
      reports of low back pain (LBP) in adolescents each year over a five-year period
      (between the ages of 13 and 17 years). METHOD: A longitudinal, observational,
      repeated-measures study, commencing in 1999. We followed a group of South
      Australian students throughout five years of high schooling, reporting on
      prevalence of recent low back pain each year. RESULTS: In 1999, data were
      collected from 434 13-year-olds (82.5% eligible students). In the subsequent four
      years, the response rate from the 1999 sample was, respectively, 72.2%, 69.1%,
      56.2% and 40.1%. A significant increasing prevalence of recent LBP was reported
      for girls and boys. The odds of girls reporting recent LBP in the final study
      year (fifth year) compared with the first year was 4.4 (95% CI 1.9-10.1),for boys
      1.6 (95% CI 0.7-3.7). New cases of girls' recent LBP decreased consistently over
      the study (90% in 2000, 46.1% in 2001, 42.1% in 2002 and 33% in 2003). New boys'
      cases decreased in the second and third study years (85% in 2000, 45% in 2001)
      then increased (45.8% in 2002, 63.6% in 2003), suggesting less established
      patterns of occurrence. CONCLUSIONS: New cases of LBP reflected a decreasing
      percentage of total LBP reports over each study year for girls (suggesting
      increasing consistency of LBP occurrence with age). A different pattern was
      observed for boys, with a reversal of the downward trend after age 15 years,
      showing an increased percentage of LBP reports that reflected new cases in the
      final two study years.

PMID- 17019947
TI  - Changes in gait and symptoms after bilateral pallidotomy: a client with
      Parkinson's disease.
AB  - A single-subject, time-series design was used to describe a female with young
      onset Parkinson's disease who, after a period of 15 years, was demonstrating long
      term side effects of medication in addition to the progression of Parkinson's
      disease. She underwent a bilateral pallidotomy to address these problems. Prior
      to her surgery, her spatiotemporal gait kinematics were measured at intervals
      before and after medication ingestion. The identical procedures were undertaken
      one month and at four months post-pallidotomy. In all three sessions, the Webster
      Scale scored her symptoms while her medication was not working (Off) and again
      when effective (On). After surgery, she was interviewed to obtain a qualitative
      impression of the outcome. Before the surgery, the gait parameters demonstrated a
      fluctuating profile. Forty-five minutes post-medication, her gait parameters
      approached normal levels but significant dyskinetic movements were evident. Her
      Webster Scale scores indicated advanced Parkinson's disease particularly when Off
      One-month post-pallidotomy, her gait parameters were more consistent with
      dyskinesias mildly present. Her Webster Scale scores were reduced while both Off
      and On. Four months post-pallidotomy her gait parameters were entirely consistent
      and within normal limits. Her Webster Scale scores were the same Off and On and
      no dyskinesias were detectable. The excellent result was probably enhanced by the
      patient's dedication to regular exercise designed to minimize secondary physical
      complications.

PMID- 17019948
TI  - Case report: clinical dilemma--acute on chronic respiratory failure complicated
      by acute lobar atelectasis.

PMID- 17019949
TI  - Raine: a response.

PMID- 17019950
TI  - [Pulmonary edema. Physiology of pulmonary circulation and pathophysiology of
      pulmonary edema].

PMID- 17019951
TI  - [Metabolism of the main substance of the connective tissue in chronic obstructive
      pulmonary disease].
AB  - AIM: To reveal metabolic disturbances of connective tissue main substance in
      chronic obstructive pulmonary disease (COPD) and to assess their informative
      value in determination of treatment efficacy. MATERIAL AND METHODS: Peripheral
      blood of 130 COPD patients was studied for total glycosaminoglycanes,
      hyaluronidase activity, sialic acids fractions (free, oligobound and
      proteinbound), fucose fractions (oligobound and proteinbound) and activity of
      sialidase. RESULTS: The levels of total glycosaminoglycanes, sialo- and fucose
      containing compounds in the blood change with COPD severity and phase of the
      disease. CONCLUSION: The data obtained may be used to assess activity of
      respiratory inflammation and efficacy of the treatment.

PMID- 17019952
TI  - [Relations between VDR3 and COL1A1 genes and markers of bone tissue metabolism in
      patients with chronic obstructive pulmonary disease].
AB  - AIM: To study correlation between polymorphism of the genes of vitamin D3 (VDR3),
      collagen of type 1 alpha-1 (COL1A1) and markers of bone tissue metabolism in
      chronic obstructive pulmonary disease MATERIAL AND METHODS: A total of 56 COPD
      patients were examined. Bone metabolism was evaluated by osteocalcin (OC) level
      and betaCL in the blood; BsmI polymorphism of gene VDR3 (genotypes BB, Bb, bb)
      and Sp1 polymorphism of gene COL1A1 (genotypes SS, Ss, ss)--by polymerase chain
      reaction. The control group consisted of 50 healthy persons of matched gender and
      age. RESULTS: OC and S allele were not the same in genotypes BB, Bb and bb. Ss
      and ss genotypes carriers had higher beta CL level than SS-carriers. SS and ss
      genotypes carriers did not differ with betaCL concentrations (p > 0.05).
      CONCLUSION: Testing of VDR3 and COL1A1 genes gives grounds for detection of
      predisposition to development of pulmonogenic osteopenic syndrome.

PMID- 17019953
TI  - [Pharmacotherapeutic assessment of antiosteoporotic properties of alpha-calcidol
      in chronic obstructive pulmonary disease].
AB  - AIM: To evaluate antiresorptive properties of alphacalcidol in the treatment of
      osteopenic syndrome in patients with chronic obstructive pulmonary disease
      (COPD). MATERIAL AND METHODS: A total of 94 COPD patients with low densitometric
      indices were studied for bone densitometric parameters, calcium-phosphorus
      metabolism, markers of bone tissue metabolism (osteocalcine-OC, tartrate
      resistent acid phosphatase--TRAP, beta CrossLaps - BCL), cytokine profile in the
      course of 6-month continuous therapy with alpha-calcidol (alpha-D3-TEVA) in a
      dose 0.75-1 mcg/day. RESULTS: Six-month treatment with alpha-calcidol relieved
      pain, increased bone densitometric parameters, normalized calcium-phosphorus
      metabolism. While 3-month therapy induced positive dynamics in markers of bone
      metabolism (OC level increased, concentrations of BCL, TRAP reduced), 6-month
      therapy resulted in these parameters normalization close to the level of healthy
      persons. Proinflammatory cytokines (IL-1beta, IL-6 TNF-alpha) in COPD lowered
      significantly. CONCLUSION: Alpha-calcidol have analgetic, antiresorptive and
      immunomodulating effects which make this drug effective in prevention and
      pathogenetic therapy of osteopenic syndrome in COPD.

PMID- 17019955
TI  - [Respiratory infection in patients with bronchial asthma. Clinicolaboratory
      characteristics].
AB  - AIM: To study clinicolaboratory signs of respiratory infection in patients with
      bronchial asthma (BA). MATERIAL AND METHODS: Respiratory infection and its
      influence on BA were studied in 108 BA patients (66 female and 42 male, mean age
      51.0 +/- 15.2 years) with symptoms of bronchitis and non-nosocomial (n = 71) and
      nosocomial (n = 37) pneumonia. The patients referred for medical care and started
      antibacterial therapy (ABT) after 4.7 +/- 2.8 days of respiratory infection (RI).
      Before assignment to the trial BA exacerbation ran for 9.8 +/- 6.0 days. RESULTS:
      RI preceded BA exacerbation in 62% patients with pneumonia. BA exacerbation
      preceded RI in 66% patients with bronchitis. RI ran with moderate and severe
      intoxication. Severity of BA exacerbation correlated with severity of RI
      Antibacterial treatment was uneffective and the drugs were changed for others in
      18% bronchitis and 16% pneumonia patients. Laboratory signs of inflammation were
      more obvious in pneumonias than in bronchitis and did not depend on the disease
      severity. External respiration function at RI onset was significantly affected in
      all the patients. CONCLUSION: Respiratory infections aggravate the course of BA
      and damage external respiration function.

PMID- 17019954
TI  - [Clinicomicrobiological monitoring of patients with exacerbation of chronic
      bronchitis treated with antibacterial drugs].
AB  - AIM: To compare clinical and microbiological efficacy of penicillines and
      macrolids in patients with exacerbation of chronic bronchitis (CB) basing on long
      term follow-up after antibacterial treatment. MATERIALS AND METHODS: Twenty
      patients with exacerbated CB or chronic obstructive pulmonary disease (COPD)
      received amoxicillin/clavulanic acid (augmentin) while 20 other patients were
      given macrolides (sumamed or clacide). Clinical efficacy was assessed by the rate
      of exacerbation regression and duration of recurrence-free period in the course
      of 12-month follow-up. Bacteriological examination was conducted 3-5 days, 1
      month after the treatment and at recurrent exacerbation. RESULTS: Patients on
      augmentin showed faster regression of exacerbation, earlier remission and higher
      quality of remission than patients on macrolides. Eradication of etiologically
      significant pathogens on day 3-5 after therapy with augmentin and macrolides was
      achieved in 92 and 30% patients, respectively, persistence--in 8 and 70%,
      respectively. Mean duration of remission was 263 +/- 107.1 and 164.9 +/- 112,2
      days, respectively. A correlation was found between duration of recurrence-free
      period and frequency of eradication and persistence of the agents after
      antibacterial therapy of CB and COPD. CONCLUSION: Augmentin promotes a
      significantly earlier regress of exacerbation symptoms and persistent remission.
      Eradication potential of augmentin in CB/COPD patients is higher than that of
      macrolides. Long-term post-exacerbation monitoring (12-month follow-up)
      discovered that recurrence-free period of augmentin-treated patients is much
      longer than in patients on macrolides.

PMID- 17019956
TI  - [Clinical efficacy of target low-intensity laser radiation on the adrenal
      projection region in patients with bronchial asthma].
AB  - AIM: To study efficacy of infrared laser radiation on the adrenal projection
      region in patients with bronchial asthma (BA). MATERIAL AND METHODS: The adrenal
      region of BA patients was exposed to infrared laser radiation. The effect was
      stated after blood count, examination of the urine and sputum, blood biochemical
      tests, blood hydrocortisone assay. RESULTS: Positive clinical response to laser
      therapy manifested with improvement of clinical, device and spirometric indices
      in BA patients. Blood levels of hydrocortisone normalized. CONCLUSION: Infrared
      laser radiation of adrenal projection region reduced the number of asphyxia
      attacks, improved bronchial drainage, shortened the disease duration. The method
      is well tolerated, safe, easy to make and suggested for use in combined treatment
      of BA.

PMID- 17019957
TI  - [Outpatient use of laser therapy in bronchial asthma].
AB  - AIM: To analyse effects of outpatient laser therapy on the course of different
      forms of bronchial asthma (BA). MATERIAL AND METHODS: The examination has covered
      466 patients with BA divided into three groups: group 1 patients received
      monotherapy with low-intensive laser radiation (LILR); group 2 - LILR plus
      conventional drug therapy (CDT); group 3 - CDT only. RESULTS: Group 1 and 2
      patients achieved improvement after 2-3 sessions. Asphyxia attacks were less
      frequent and severe. These attacks disappeared to session 7-10, 10-12 in patients
      with exogenic, endogenic and mild, moderate mixed BA, respectively. The patients
      recovered sensitivity to sympathomimetics and methylxantines.
      Glucocorticosteroids (GCS) doses, hospital stay and temporary disability duration
      decreased. These two groups achieved remission within 0.5-1 year in 50% patients.
      Remission for 1-2 years was observed in 40% patients while in group. 3 - in 14%.
      CONCLUSION: The addition of laser therapy improves a BA course, results of
      outpatient treatment and rehabilitation, recovers bronchial sensitivity to
      sympathomimetics and xantine derivatives, reduces GCS dose and duration of
      hospital stay and disability in BA patients.

PMID- 17019958
TI  - [The influence of cardiopulmonary bypass on respiratory function in an early
      postoperative period].
AB  - AIM: To investigate the influence of cardiopulmonary bypass (CPB) on pulmonary
      function early after the operation by evaluating Qs/Qt. MATERIAL AND METHODS:
      Twenty one patients after elective myocardial revascularization surgery have been
      analysed. Group 1 included 11 patients who have undergone cardiac surgery with
      CPB. Group 2 included 10 patients who have undergone cardiac surgery without CPB.
      Blood gas analysis for intrapulmonary shunt calculations was made 20 minutes
      after the induction of anesthesia and 4 hours after surgery. Qs/Qt was also
      calculated. RESULTS: Four hours after surgery Qs/Qt increased compared to
      preoperative data in group 1 (from 8.6 +/- 2.1 to 16.8 +/- 2.6%, p < 0.02).
      Intrapulmonary shunt was greater in group 1 vs group 2 four hours after the
      surgery (16.8 +/- 2.6 and 7.8 +/- 2.1%, p < 0.02). In group 1, alterations in a
      pulmonary function (81.8%) were caused by atelectasis detected by chest x-ray. In
      group 2 neither increase in intrapulmonary shunt nor atelectasis were determined.
      CONCLUSION: Arterial hypoxemia and an increase in the intrapulmonary shunt (due
      to atelectasis) have proven that alterations in the pulmonary function occur more
      often and are more pronounced in patients after surgery with cardiopulmonary
      bypass.

PMID- 17019959
TI  - [Arterial hypertension in schizophrenia as a model of benign transformation of
      somatic pathology].
AB  - AIM: To detect characteristics of arterial hypertension in schizophrenia.
      MATERIAL AND METHODS: The course of arterial hypertension and structural
      functional alterations of the left ventricle were studied in the group of
      hypertensive schizophrenics and hypertensive patients without schizophrenia.
      RESULTS: Arterial hypertension in schizophrenics occurs less frequently, is not
      so high, is associated with insignificant structural-functional rearrangement of
      the left ventricle. This is true for cases when arterial hypertension onset
      precedes onset of psychosis when somatic disease does not combine with
      atherosclerosis. Incidence rate of hypertension diagnosis, mean levels of
      pressure and structural-functional indices of the left ventricle (for the first
      degree of arterial hypertension) for patients given and not given vasoactive
      psychotropic drugs do not differ significantly. CONCLUSION: Arterial hypertension
      in schizophrenia is characterized by benign transformation as seen from less
      prevalence and severity of the disease in mild structural-functional alterations
      of the left ventricle than in population of somatic patients.

PMID- 17019960
TI  - [Trends in heart rate variability in patients with ischemic heart disease and
      depression treated with antidepressant tianeptine].
AB  - AIM: To study heart rate variability (HRV) according to 24-h Holter monitoring of
      ECG in patients with ischemic heart disease (IHD) and to examine effects of
      tianeptine on HRV. MATERIAL AND METHODS: Twenty eight patients with IHD (17 males
      and 11 females aged 40-70 years) with a verified IHD diagnosis and
      atherosclerosis of the coronary arteries participated in the trial. Severity of
      depressive syndrome was assessed by CES-D questionnaire. HR V was assessed by
      weighted mean variation of the rhythmogram (WMVR) for 24 hours. RESULTS: Initial
      WMVR (m +/- sigma) in the study group (IHD with depression, n = 15) was 670 +/-
      260 ms, in the control group (IHD without depression, n = 13) - 625 +/- 191 ms
      (the difference was insignificant (p = 0.72). Initial (m +/- sigma) WMVR in men
      of the study group (n = 6) before therapy was 460 +/- 139 ms that was less than
      in the control group (633 +/- 183 ms, n = 11). CONCLUSION: In men HRV depends on
      duration of the disease. There was a negative correlation between WMVR difference
      before and after treatment with tianeptine and difference of relevant depression
      indices with high correlation coefficient (-0.74, p = 0.03).

PMID- 17019961
TI  - [Spiriva (thiotropium bromide)--an effective drug for chronic obstructive
      pulmonary disease].

PMID- 17019962
TI  - [Acute bronchitis in adults].

PMID- 17019963
TI  - [The role of hereditary factors in development of pulmonary emphysema].

PMID- 17019964
TI  - [Correction of mucociliary insufficiency: present-day modalities and
      perspectives].

PMID- 17019965
TI  - [Defects in mineral density of bone tissue in patients with celiac disease].

PMID- 17019966
TI  - [Inflammation as a risk factor for restenosis and cardiovascular complications
      after transcutaneous intracoronary interventions].

PMID- 17019967
TI  - Transformation in lymphomas--morphological, immunophenotypic and molecular
      features.
AB  - During the course of lymphoma, a clinically more aggressive process with
      different morphology may develop, referred to as lymphoma transformation. Clonal
      relationship and pathogenic mechanism of this process are widely debated. The aim
      of the study was to evaluate morphology, immunophenotype (including EBV status)
      and clonal relationship in nine cases of lymphoma transformation. Among the six
      patients with low grade B-cell lymphomas three transformed into high grade B-cell
      lymphomas (two into diffuse large B-cell lymphoma, one into Burkitt lymphoma) and
      three into Hodgkin lymphoma. Three other patients with Hodgkin lymphoma presented
      with transformation into diffuse large B-cell lymphoma in two patients and
      peripheral T-cell lymphoma in one patient. In all cases there was a sudden
      clinical change as well as change in morphology and phenotype. In five of the
      nine patients studied EBV-LMP1 was demonstrated by immunohistochemistry in large
      transformed lymphoma cells. In two cases molecular studies revealed a different
      pattern of immunoglobulin gene rearrangement in the large transformed cells as
      compared to the small cells of primary indolent lymphoma. Thus, they represented
      secondary, arising de novo neoplasm.

PMID- 17019968
TI  - Disturbances of the expression of metalloproteinases and their tissue inhibitors
      cause destruction of the basement membrane in pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease which
      pathogenesis is associated with destruction of the basement membrane components
      and the anchoring fibers. The binding of autoantibodies to antigens localized in
      the basement membrane of the epidermis activates a series of immunological and
      enzymatic phenomena that lead to blister formation. There are some data that MMPs
      are involved in the development of skin lesions in BP, however their exact role
      in this process is not fully understood. We aimed to investigate whether MMPs and
      their inhibitors (TIMPs), assessed by their tissue expression, are involved in
      the pathogenesis of BP. The localization and expression of collagenase (MMP1),
      gelatinase (MMP2), 92 kD gelatinase (MMP9) and stromelysin 2 (MMP10) and TIMP1,
      2, 3 were examined by immunohistochemistry in skin biopsies as well as in normal
      human skin specimens. The study included 21 patients with BP at an active stage
      of the disease. The MMPs and TIMPs serum levels were measured by ELISA method.
      Expression of MMP1, MMP2, MMP9 and MMP10 was observed either in the whole
      epidermis or in the basal keratinocytes. Most of the enzymes examined, apart from
      TIMP3, were detected in dermal part of the blister. Expression of the majority of
      the enzymes examined was observed in blister fluid however, the most intense
      signal was noted for MMP10. In cellular infiltrate we found expression of all the
      MMPs and TIMPs, the most distinct for MMP1, MMP2, MMP10 and for TIMP2. In all
      biopsies obtained from healthy volunteers only single basal keratinocytes gave
      positive, weak signal for the examined proteins. The MMPs and TIMPs serum levels
      in the control group were normal while in some cases of BP patients they were
      increased. Based on the results we conclude that imbalance between these enzymes
      really occurs in BP and it is likely to take important part in the pathogenesis
      of the disease.

PMID- 17019969
TI  - Analysis of TGF-beta protein expression in aggressive fibromatosis (desmoid
      tumor).
AB  - Aggressive fibromatosis, usually termed desmoid tumor, develops from muscle
      connective tissue, fasciae and aponeuroses. Aggressive fibromatosis located in
      various parts of the body demonstrates differentiated biological behavior.
      Abnormalities in TGF-beta expression are very common in many disease processes,
      including neoplasms. Immunohistochemical analysis employing a monoclonal antibody
      against TGF-beta was performed on archival material, consisting of 38 cases of
      aggressive fibromatosis, among which 23 represented abdominal, 11 extra-abdominal
      and 4 intra-abdominal localizations. The sections for immunohistochemical study
      were stained using the streptavidin-biotin (ABC) method. The average percentage
      of cells positively stained for TGF-beta protein was 40.2% in the group of extra
      abdominal, 58.5% in the group of abdominal and 72.8% in the group of intra
      abdominal localizations. There were significant differences observed between the
      analyzed groups of desmoid tumor (p<0.05). A positive cytoplasmic reaction for
      TGF-beta was noted in 65.8% (25/38) of the aggressive fibromatoses.
      Overexpression of TGF-beta protein was noted in 39.5% (15/38) of the aggressive
      fibromatoses. High expression noticed in desmoid fibroblasts might indicate that
      this protein plays a crucial role in the development of aggressive fibromatosis.

PMID- 17019970
TI  - Loss of heterozygosity and microsatellite instability at RAD52 and RAD54 loci in
      breast cancer.
AB  - This study was carried out to evaluate the loss of heterozygosity (LOH) and
      microsatellite instability (MSI) in breast cancer, in the 12p13.3 and 1p32
      chromosomal regions where RAD52 and RAD54 genes are localized. Polymorphic
      markers D12S98, D12S1698 for RAD52 and D1S209, D1S411 for RAD54 were used.
      Relationships between LOH and clinicopathological parameters, i.e. tumor type and
      grade, patient's age, steroid receptors status and lymph node and distal
      metastases were assessed. For alleles frequency estimation 100 primary breast
      cancers were tested. DNA isolated from paraffin-embedded tissues and their
      matched blood samples were analyzed for PCR-based LOH and MSI by fluorescence
      based DNA sequencing technology. In analyzed cases LOH was found in 14% and 11%
      of informative cases for D12S98 and D12S1698 markers, respectively and in 18% and
      17% of informative cases for D1S209 and D1S411 markers, respectively. The highest
      frequency of MSI was identified at loci D12S98 (10%) and D1S209 (11%).
      Significant correlations between RAD52 and RAD54 regions with concomitant LOH and
      histological type and progesterone receptor status were observed. In the case of
      RAD54 further correlations with respect to tumor grade and the presence of distal
      metastases were noticed.

PMID- 17019971
TI  - Sodium metavanadate affected control and streptozotocin-diabetic rat liver golgi
      complexes.
AB  - As we have observed previously, rat liver Golgi complexes are very useful cell
      organelle in investigating the effectiveness of various drugs with cytoprotective
      or normalizing activities in streptozotocin (STZ)-induced diabetes. The diabetes
      associated biochemical and morphological alterations in the organelle were
      investigated in four groups of rats: control and STZ-diabetic (C and D groups)
      and compared with the same groups treated with 1.5 mM metavanadate administered
      as drinking solutions in 0.09 M NaCl over 7 days (C+V and D+V groups). Apart from
      the untreated group C, a decrease of body weight during the experiment was noted
      in the remaining three groups, reaching a statistically significant level in the
      diabetic groups (c. 15%). Fluid and food intake were statistically significantly
      (p<0.001) limited in both the vanadium treated groups. In the diabetic group
      treated with metavanadate, the free blood sugar level decreased, but euglycemia
      was not achieved. In groups C+V, D and D+V, the activity of Golgi marker enzyme,
      i.e. galactosyltransferase (GalT), was statistically lower as compared with group
      C (p<0.001). The treatment of diabetic rats with 1.5 mM NaVO3 [V(V)I in 0.09 M
      NaCl as a drinking solution during 7 days did not normalize the yield of Golgi
      membrane preparations or the Golgi marker enzyme activity. Electron microscopy
      revealed marked ultrastructural changes triggered by the employed vanadium
      compound. A striking change was seen in the presence of giant intracytoplasmic
      vacuoles. These alterations were seen in both experimental groups, i.e. C+V and
      D+V. Group C+V showed more advanced ultrastructural changes, what was expressed
      in a poorer state of mitochondrial membranes, a greater number of vesicular
      structures and less frequently seen Golgi structures. In spite of the fact that
      the animals were exposed to two compounds with a strong biological activity, the
      group of diabetic rats treated with metavanadate (D+V) showed no such advanced
      changes: more numerous Golgi structures were noted and their form was practically
      ring-like, i.e. characteristic for this group of organelles.

PMID- 17019972
TI  - Tissue microarray FISH applied to colorectal carcinomas with various
      microsatellite status.
AB  - Colorectal carcinoma is etiopathologically heterogenic. It may develop through a
      sequence of mutations leading to chromosome instability or be a result of defects
      in DNA repair mechanisms manifested by microsatellite instability of varying
      degrees. Colorectal carcinoma can thus be classified into microsatellite-stable
      (MSS), highly microsatellite unstable (MSI-H) and intermediate low-level
      microsatellite unstable (MSI-L) groups. Fluorescent hybridization in situ (FISH)
      is a method of detecting specific sequences of nucleic acids that is based on
      specific bonding of a fluorescent marker-associated probe and specific DNA
      fragment. The material consisted of 146 non-selected cases of colorectal
      carcinoma patients operated on at First Chair of General Surgery, Collegium
      Medicum, Jagiellonian University in Cracow, Poland. Following a standard
      histopathological evaluation, tissue microarrays were prepared using a Tissue
      MicroArray Builder, and FISH was performed employing probes specific for
      chromosomes 1, 8, 17 and 18. Microsatellite instability was evaluated in frozen
      material using the PCR reaction with gel and capillary electrophoresis. The mean
      number of signals obtained for chromosome 1 in the entire material was 2.06,
      while the corresponding mean values in the MSS group equaled 2.07, in the MSI-L
      group - 2.07, and in the MSI-H group - 2.01. The mean number of signals for
      chromosome 17 in the entire material was 2.1, in the MSS group - 2.11, in the MSI
      L group - 2.13, and in the MSI-H group - 2.01. The number of signals for
      chromosome 18 in the entire material was 2, in the MSS group - 2, in the MSI-L
      group - 2, and in the MSI-H group - 2. The means number of signals for chromosome
      8 in the entire material was 2.07, in the MSS group - 2.08, in the MSI-L group -
      2.01, and in the MSI-H group - 2. These differences are not sufficient for
      distinguishing colorectal carcinoma molecular forms.

PMID- 17019973
TI  - Correlation of microsatellite status, proliferation, apoptotic and selected
      immunohistochemical markers in colorectal carcinoma studied with tissue
      microarray.
AB  - Colorectal carcinoma is a frequent malignant tumor, characterized by varying
      clinical course and response to treatment. At the molecular level, colorectal
      carcinomas are divided into tumors with chromosomal instability (microsatellite
      stable, MSS), microsatellite instability (MSI-H) and low microsatellite
      instability (MSI-L). The method of tissue microarrays allows for combining
      materials originating from multiple patients into a single slide, what makes
      possible to simultaneously investigate large material for the presence of
      numerous, diversified markers. The study material consisted of 208 cases of
      colorectal carcinoma. Microsatellite instability was evaluated in frozen material
      employing the PCR reaction with gel and capillary electrophoresis. Following a
      standard histopathological assessment, tissue microarrays were prepared using a
      MTA-1 microarrayer (Beecher) and standard immunohistochemical reactions were
      performed to detect the presence of bcl-2, CDX-2, Ki67, MLH1, MSH2, MSH6, p16,
      p53 and survivin. Apoptotic cells were detected using the TUNEL method. The
      correlations between the reactions were investigated and differences in the
      expression of the investigated proteins noted in carcinomas with various degrees
      of microsatellite instability. The agglomeration analysis showed differences in
      patterns of expression between MSS, MSI-L and MSI-H carcinomas. The discriminant
      function analysis demonstrated that the MSI-H carcinomas were best differentiated
      by MLH1, survivin and Ki67 expression, while the MSI-L tumors differed from the
      remaining colorectal carcinomas by their apoptotic index, local tumor stage (pT),
      the presence of angioinvasion and mucin production.

PMID- 17019974
TI  - Pathological analysis of lesions within intestines resected due to ulcerative
      colitis.
AB  - INTRODUCTION: Ulcerative colitis (UC) and Lesniowski-Crohn's disease together
      constitute a type of intestinal pathology known as Inflammatory Bowel Disease.
      The etiology of UC still remains unknown, however some epidemiological data
      suggest the role of bacteria and viruses and also some habitual as well as
      environmental factors like smoking, diet, drugs, geographical and social status,
      as well as stress. The genetic predisposition is also suggested. UC affects young
      people in 2nd - 4th decades of life. Exacerbations of the disease may result in
      the necessity of surgical treatment, typically in the form of total
      proctocolectomy accompanied by the subsequent formation of ileo-pouch-anal
      anastomosis. The aim of our study was to analyze morphological pictures of
      resected specimens. MATERIAL AND METHODS: We analyzed 67 cases (40 women and 27
      men) of UC with the special interest being focused at macro- as well as
      microscopic features of the intestines resected. We reviewed macroscopic
      characteristics of intestines (i.e. the length of resected fragments,
      localization, shape and diameter of the ulcers, polyps, number of resected lymph
      nodes), as well as microscopic descriptions concerning, among others the
      character and localization of inflammatory infiltrate, the architecture of
      glands, the presence of crypt abscesses and Paneth's metaplasia. Special
      attention was paid to the morphology of intestinal wall vasculature. RESULTS: In
      42% of the cases macroscopically the inflammation covered the whole length of the
      resected colon. In 58% macroscopically detected inflammatory changes were
      segmental in distribution. In four cases the disease had clinically the fulminant
      course and the inflammation was transmural. There were 3 cases, in which
      histological assessment revealed the presence of malignancy (2 cases of mucus
      producing adenocarcinoma and one case of carcinoma in situ situated in the anal
      canal). Generally, microscopic findings were typical for the active phase of UC.
      We found intensive vascularization and hyperemia of the intestinal wall to be the
      common features accompanying the inflammation. CONCLUSIONS: Young people in the
      3rd and 4th decades of life constitute the group being relatively commonly
      affected by the UC, and undergo the surgical proctocolectomy. Some of the cases
      present with the fulminant course of the disease. A rich vascular network is a
      common finding in the inflamed intestinal wall. We hypothesize, that intensive
      vascularization may play a significant role in the pathogenesis of UC.

PMID- 17019975
TI  - Morphological and molecular diagnosis of a fatal form of EBV infectious
      mononucleosis in a child.
AB  - Mortal cases of acute Epstein-Barr virus (EBV) infection in the form of
      mononucleosis have been seldom described and used to be related to complications
      of the disease. In this report, the case of a 3-year-old girl is described, with
      severe form of infectious mononucleosis, deceased in the course of respiratory
      circulatory insufficiency with a sudden cessation of heart action. Particular
      attention was given to histological lesions, phenotype of inflammatory cells and
      to expression of proteins and EBV RNAs (EBERs) in tissues, examined using
      immunocytochemical techniques and in situ hybridization. Histological patterns
      were dominated by massive lymphocyte infiltrates (mostly CD45RO+ and CD3+ cells),
      mainly in lungs and in liver and, less pronounced, in kidneys and in leptomeninx.
      Lymphocyte proliferation exhibited polyclonal character: both lambda and kappa
      chains were present. No myeloblastic differentiation could be demonstrated. The
      EBV proteins, as well as EBV RNAs (EBERs) were detected both in small lymphocytes
      B and in enlarged (blast) cells, frequently resembling Reed-Sternberg cells. In
      our tissue material co-expression of the two proteins (EBNA2+, LMP1+) and EBER
      has been demonstrated in every organ, in accordance to the latency III pattern
      described by other authors.

PMID- 17019976
TI  - Predictors of response to cardiac resynchronization therapy--importance of left
      ventricular dyssynchrony.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is currently used in selected
      patients with dilated cardiomyopathy and heart failure. However, 30% of patients
      do not respond to CRT when selection is based on clinical and
      electrocardiographic criteria. Left ventricular dyssynchrony can be evaluated by
      tissue Doppler imaging and it has been described as a useful precdictor of
      response to CRT. OBJECTIVE: To evaluate whether left ventricular dyssynchrony, as
      measured by tissue Doppler imaging, can be used to predict response to CRT.
      METHODS: 23 consecutive patients (age 67 +/- 10 years, 13 male) with heart
      failure refractory to medical therapy and who underwent CRT were studied. Before
      and six months after the procedure, various characteristics - clinical (including
      NYHA functional class), electrocardiographic (QRS interval) and echocardiographic
      (left ventricular ejection fraction [EF] and respective volumes)--were evaluated.
      In addition, pulsed wave tissue Doppler imaging was used to assess the time
      interval (QS) between the beginning of the QRS complex and the beginning of the
      systolic wave on the Doppler signal, in the basal segments of the septal,
      lateral, anterior and inferior walls. Left ventricular dyssynchrony was
      quantified as the difference between the maximum and minimum QS interval (QS(max
      min)). The patients were divide into two groups: responders, if functional class
      improved by at least one and EF increased by more than 10%, and non-responders
      for the remainder. Differences between groups were assessed and predictors of
      response to CRT were determined. RESULTS: CRT improved functional class by at
      least one in 87% of patients and EF improved from 21 +/- 6 to 33 +/- 9% (p <
      0.001). QS(max-min) was reduced from 80 +/- 38 to 38 +/- 14 ms (p < 0.001). In 15
      patients (65%), classified as responders, there was an improvement in functional
      class and an increase in EF of more than 10%. There were no differences between
      groups, except for QS(max-min). Patients in the responder group had greater left
      ventricular dyssynchrony (QS(max-min) 94 +/- 39 vs. 54 +/- 16 ms, p = 0.002).
      QSmix-min was an independent predictor of response to CRT and a cut-off of 60 ms
      identified responders with a sensitivity of 87% and specificity of 75%.
      CONCLUSION: Despite the good results achieved with CRT, about one third of
      patients do not benefit from it. Left ventricular dyssynchrony can be quantified
      by tissue Doppler imaging using QS(max-min) and values greater than 60 ms can
      identify responders to CRT.

PMID- 17019977
TI  - Cardiac resynchronization therapy: which is the best method of selecting
      patients?

PMID- 17019978
TI  - Aortic valve replacement with anterior and posterior enlargement of small aortic
      annulus is comparable to surgery with normal annulus.
AB  - OBJECTIVE: To compare results of aortic valve replacement in patients with normal
      annulus and in those undergoing anterior and posterior enlargement of a small
      annulus to implant a larger prosthesis. METHODS: The study included 22 patients
      with enlargement of a small aortic annulus and 23 with a normal aortic annulus,
      with similar demographic characteristics and selected from a large surgical
      population. For normal annulus, simple valve replacement was performed. For
      annular enlargement, the posterior approach required incision in the mid portion
      of the non-coronary sinus, up to the anterior mitral leaflet; anterior
      enlargement was achieved by an incision between the left and right coronary
      ostium, extended to the ventricular septum for 2 cm. The aorta was reconstructed
      with bovine pericardium patches. The results analyzed included diameter of aortic
      annulus at surgery, clinical evolution (2 to 11 years of follow-up), left outflow
      tract obstruction and left ventricular mass (by Doppler echocardiography).
      RESULTS: Enlargement increased the aortic annulus from 18.3 +/- 2.2 mm to 24.8 +/
      2.0 mm (p < 0.001), a value similar to aortic annulus considered normal: 24.9 +/
      1.5 mm (NS). For annular enlargement, the peak systolic gradient at the
      prosthesis decreased from 83.6 +/- 22.3 mmHg (preoperative) to 26.7 +/- 11.4 mmHg
      (p < 0.01) at the last evaluation. For normal annulus, a reduction from 68.2 +/-
      28.7 mmHg to 32.8 +/- 16.2 mmHg occurred (p < 0.001) (final values similar
      between groups; NS). Left ventricular mass at the last evaluation was 147.2 +/-
      45.9 for patients with enlargement and 148.1 +/- 70.4 for those with normal
      annulus. CONCLUSION: Anterior and posterior aortic annulus enlargement enabled
      increases in annular diameter and valve prosthesis size, providing clinical and
      echocardiographic results similar to patients with valve replacement in a normal
      annulus.

PMID- 17019979
TI  - Papillary fibroelastoma located deep in the left ventricle: case study and
      literature review.
AB  - The authors report a case of a 68-year-old male, with no known cardiac disease
      until he suffered a cerebral embolic event related to the presence of a papillary
      fibroelastoma located in the mid third of the inferior left ventricular wall.
      They also perform a literature review, particularly of the specific
      characteristics of the tumor and the surgical approach. They point out that the
      location of the fibroelastoma described is very unusual; its clinical and
      echocardiographic characteristics are similar to those described for
      fibroelastomas with this location and the surgical approach should be decided for
      each individual patient. Thus transaortotomy, which provided better visualization
      and enabled complete removal of the tumor (which is essential for good clinical
      evolution and to avoid recurrence), was the option for surgical removal of this
      tumor.

PMID- 17019980
TI  - Detection of preclinical left ventricular dysfunction in Fabry disease: the
      contribution of tissue Doppler.
AB  - INTRODUCTION: Fabry disease is a rare X-linked lysosomal storage disorder caused
      by a deficiency of alpha-galactosidase, which results in progressive
      intracellular accumulation of glycosphingolipids in various tissues. Cardiac
      involvement is frequent, with left ventricular (LV) hypertrophy (concentric,
      apical or asymmetric septal) as the most common finding. Evaluating LV systolic
      dysfunction with conventional echocardiography is not sufficiently sensitive to
      detect impaired myocardial function early in the course of the disease. Doppler
      myocardial imaging can quantify changes in global and regional longitudinal
      myocardial function with great precision. AIM: To identify parameters of cardiac
      dysfunction in patients with Fabry disease with no cardiac symptoms using
      conventional or Doppler echocardiography and tissue Doppler (including tissue
      tracking, strain and strain rate). METHODS: Four patients with Fabry disease (3
      female; mean age 47 +/- 17 years) and 29 healthy controls (19 female and 10 male;
      mean age 38 +/- 14 years) were studied with conventional echocardiography and
      tissue Doppler imaging using a Vivid 7 scanner. The following parameters were
      measured: LV dimensions, ejection fraction (using Simpson's rule), systolic and
      diastolic velocities and tissue tracking of the mitral annulus at six sites
      (apical views). LV peak systolic strain and strain rate were obtained in 12
      segments from apical views. RESULTS: Two patients had LV hypertrophy (one
      concentric and one apical). Diastolic impairment was detected in three patients
      by reduced flow propagation velocity of early transmitral flow (Vp) and E/Vp
      ratio. Mitral annulus systolic velocities were lower in Fabry disease than in the
      controls. Peak systolic strain and strain rate were diminished in all segments in
      three patients, showing impaired myocardial systolic function. The results are
      presented for each of the four patients. CONCLUSIONS: In patients with Fabry
      disease, with no cardiac symptoms and normal LV systolic function on conventional
      echocardiography, diastolic dysfunction was detected by Vp and E/Vp ratio
      regardless of LV hypertrophy. However, tissue Doppler imaging was able to detect
      impaired myocardial systolic function, particularly in patients with LV
      hypertrophy.

PMID- 17019981
TI  - Assessment of coronary artery anomalies with multislice computed tomography.

PMID- 17019982
TI  - [Portuguese Society of Cardiology recomendations, assessment and treatment of
      hypertension].

PMID- 17019983
TI  - [The influence of dopamine injected into the lateral geniculate body on flash
      visual evoked response in rats].
AB  - PURPOSE: Numerous neurotransmitters and neuromodulators operating on all levels
      of the visual system, influence the parameters of cortical evoked response. The
      aim of this study was to find the influence of dopamine (DA) injected into the
      lateral geniculate body (nucleus) on flash visual evoked response (FVEP).
      MATERIAL AND METHODS: The experiments were performed on adult Wistar rats. They
      were implanted with 1 caniula conducted into the lateral geniculate body and 2
      electrodes: active under the skull on dura mater in occipital region of brain and
      reference one on the skull in the interorbital region. FVEPs curve before and
      after injection into the lateral geniculate body 0.9% NaCl and DA were analyzed.
      RESULTS: DA in the lateral geniculate body causes increasing latency and
      amplitude of FVEP peaks. CONCLUSIONS: Dopamine in the lateral geniculate body can
      improve visual perception in the occipital cortex.

PMID- 17019984
TI  - [The influence of stimulation dopaminergic D, i D2 receptors in lateral
      geniculate body on flash visual evoked potentials (FVEP) in rats].
AB  - PURPOSE: The topic of this paper is to define the influence of stimulation
      dopaminergic D1 i D2 receptors in lateral geniculate body by flash visual evoked
      potentials (FVEP). MATERIAL AND METHODS: Wistar rats were examined. There were
      stereotaxically implanted with guide caniula into the lateral geniculate body to
      inject substances and with VEPs electrodes on the skull and on the surface of
      visual cortex. VEPs curve before and after injection into the lateral geniculate
      body: 0.9% NaCl, agonists of dopamine receptors D1 - SKF 38393, and D2 Quinpirole
      and also the same agonist after antagonists D1 - SCH 23390, i D2 Sulpiride were
      analyzed. RESULTS: Stimulating receptors D1 in the lateral geniculate body cause
      amplitude increase and shortness of latency. Quinpirole, agonist of D2 receptor
      do not significant change FVEPs curve. CONCLUSIONS: Stimulation of D1 receptors
      in the lateral geniculate body can improve visual transmission throught it and
      response in the occipital cortex.

PMID- 17019985
TI  - [The dependence of the range of fusion on some selected functions of the visual
      system. Part I: Study on convergent and divergent fusion].
AB  - After examined 132 patients, the authors selected 90 patients with correct visual
      acuity of both eyes, correct range of eyeballs' mobility, parallel setting of the
      eyeballs, no difference in refraction between both eyes and with muscular
      balance. These 90 patients were divided into 3 groups: children between 8 and 10
      years old, teenagers between 11 and 20 years old and adult people between 21 and
      40. All the groups were subject to the main examination of the study carried out
      by means of prism bar and synoptophore for each of the eye separately. The
      results were compared in order to define the difference in the range of fusion
      between both eyes. The study involved an examination of horizontal range of
      convergent and divergent synoptophoric fusion as well as that of free space for
      near and for far. A statistically significant difference between both eyes was
      observed in range of synoptophoric, for near and for far convergent fusion. The
      difference was confirmed in an average of 35.6% of patients for convergent fusion
      for near, in 34.4% of patients for convergent fusion for far, and in 65.6% of
      patients for synoptophoric convergent fusion. The mean difference between the
      eyes in the range of fusion was: 4.6 degrees for convergent fusion for near, 3.9
      degrees for convergent fusion for far and 6.4 degrees for synoptophoric
      convergent fusion. No significant differences between both eyeballs were detected
      in the range of divergent fusion. The authors suggested calling the phenomenon
      connected with the difference between both eyeballs in convergent fusion the
      following term: "visual unevenness of the range of convergent fusion".

PMID- 17019986
TI  - [The dependence of the range of fusion on some selected functions of the visual
      system. Part II: Accommodation and dominance].
AB  - This present study is the continuation of Part I of the research into the range
      of fusion in which the difference between both eyeballs as far as convergent
      fusion is concerned was described. The phenomenon was called "visual unevenness
      of the range of convergent fusion". This part of the study is devoted to the
      analysis of the relationship between the unevenness of the fusion, ocular
      dominance and accommodation. A lower range of convergent fusion was observed in
      the dominant eye with the higher accommodation, In contrast, a higher range of
      fusion was observed in the not dominant eye with lower accommodation. The authors
      think that the phenomenon of ocular unevenness of the range of convergent fusion
      does not depend on the peripheral part of visual organ. In fact, it does seem to
      point out to a cortical process. The authors suggest that quantitative tests on
      amplitude of fusion should be carried out first on the first eye and then on the
      other. The results obtained from both eyes should be compared with each other.

PMID- 17019987
TI  - [Ocular albinism in pediatric patients with nystagmus].
AB  - PURPOSE: Presentation of diagnostic methods and results obtained in childre with
      nystagmus, with suspicion of ocular albinism. MATERIAL AND METHODS: Records of 9
      children (range 0.2 to 5.5 years) are presented. In all cases family history,
      ophthalmic examination and visual evoked potentials were analyzed. RESULTS:
      Clinical signs of ocular albinism were found in all patients. 2 children had
      cutaneous albinism, VEP records of 7 children indicated abnormalities typical for
      albinism, clinical signs of gene carrying were found in 7 mothers. CONCLUSIONS:
      Clinical signs enable us to diagnose ocular albinism with relatively high
      probability, nevertheless characteristic VEP records confirm diagnosis in
      clinically difficult cases.

PMID- 17019988
TI  - [Evaluation of therapy outcome in congenital nasolacrimal duct obstruction in own
      material].
AB  - The inborn nasolacrimal duct obstruction is common ocular disease in new-borns
      and infants. There are still doubts concerning the timing of the operating
      procedure. Probing of the lacrimal ducts is the therapeutic method for this
      condition. PURPOSE: To evaluate the therapy outcome in congenital nasolacrimal
      duct obstruction in authors' own material. MATERIAL AND METHODS: In retrospective
      study of 3950 medical records of children from our Outpatient's Clinic, we
      distinguished 192 children with nasolacrimal duct obstruction. Then, we evaluated
      the outcome of implemented treatment in correlation with their age and timing of
      the nasolacrimal duct probing. RESULTS: All children with nasolacrimal duct
      obstruction had mucopurulent discharge in the lacrimal sac and lacrimation. After
      the conventional treatment, the disease resolved in 23% of our group, whereas, in
      the rest of the patients probing of the nasolacrimal duct was implemented. The
      probing was successful in all children, but it was necessary to repeat the
      procedure twice in 13 children and three times in 5 children. The success rate of
      single probing was as follows: 91% in the group of children 1 - 3 months old, 83%
      in both groups: 3 - 6 and 6 - 12 months old and 71% in the oldest group of
      children - above 1 year of age. CONCLUSIONS: In majority of children the
      nasolacrimal duct obstruction did not resolve spontaneously. Early probing within
      first few months of child's life increased the success rate of this procedure.

PMID- 17019989
TI  - [The evaluation of the expression of intercellulare adhesion molecule (ICAM-1) by
      conjunctival epithelial cells of patients with cystic fibrosis].
AB  - PURPOSE: To investigate the expression of intercellulare adhesion molecule (ICAM
      1) by conjunctival epithelialcells of patients with cystic fibrosis. MATERIAL AND
      METHODS: 15 patients with cystic fibrosis and 15 control subjects were included
      in this study. Impression cytology specimens were collected and analyzed by flow
      cytometry and analyzed by flow cytometry. RESULTS: A significant increase of ICAM
      1 expression by epithelial cells was found in patients with cystic fibrosis
      compared with normal eyes. CONCLUSIONS: Increase of ICAM-1 expression by
      epithelial cells in cystic fibrosis patients suggests, that the inflammation
      appears to have a role in the pathogenesis of the ocular surface changes and may
      be a marker of the inflammatory status in cystic fibrosis.

PMID- 17019990
TI  - [Childhood glaucoma associated with Sturge-Weber syndrome --the efficacy of
      cyclofotocoagulation and other therapeutic methods].
AB  - PURPOSE: Sturge-Weber syndrome is a rare congenital neurooculocutaneous disorder.
      Ocular involvement can include glaucoma and vascular malformations of the
      conjunctiva, episclera, choroid and retina. MATERIAL AND METHODS: 16 children (16
      eyes) with Sturge-Weber syndrome associated with glaucoma (mean age--34 month,
      mean follow up 8.87 years) treated in our institution, were reviewed. In
      retrospective analysis were assessed: IOP and postoperative complications after
      diode laser cyklophotocoagulation (16 eyes), after trabeculectomy (6 eyes) and
      trabeculectomy with MMC (3 eyes). RESULTS: In ten eyes (62.5%) good result (IOP 6
      22 mmHg) post cyclophotokoagulation--(3x) was recorded, as well as in 3 eyes
      (50%) post trabeculectomy and in 3 eyes (100%) post trabeculectomy with MMC 0.2/4
      min. No postoperative complications occured in cyclophotocoagulation group.
      Complications after trabeculectomy were the following: 3 cases of hypotony, 4
      cases with shallow anterior chamber and 5 with choroidal effusions. CONCLUSIONS:
      Diode laser cyclophotocoagulation combined with topical medication is an
      effective and safe treatment of glaucoma in children with Sturge-Weber syndrome.

PMID- 17019991
TI  - [Concentration of interleukine-8 in tears in patients with cystic fibrosis].
AB  - PURPOSE: To evaluate IL-8 concentration in tears fluid in cystic fibrosis
      patients. MATERIAL AND METHODS: Tears samples were collected from 18 CF Patients
      and 18 normal controls. Cytokine level was determined by ELISA. RESULTS: A
      significant increase of IL-8 concentration in tears fluid was found in CF
      patients compared with controls. CONCLUSIONS: Increase IL-8 concentration in
      tears fluid in CF patients suggests a role of immunologic processes in the
      pathogenesis of the ocular changes, and may be a marker of the inflammatory
      status in ocular surface in cystic fibrosis.

PMID- 17019992
TI  - Multifocal diffractive intraocular lenses in cataract surgery--preliminary
      report.
AB  - PURPOSE: Evaluation of the efficacy of multifocal, diffractive intraocular lenses
      in cataract surgery. MATERIAL AND METHODS: 20 eyes in 10 patients, mean age 64 +/
      9 years, included in the study, undergoing phacoemulsification of the cataract
      with implantation of diffractive MIOL (AcrySof ReSTOR, SA60D3, Alcon). Follow-up
      was performed for a period of 6 months. Postoperative evaluation performed five
      times included: visual acuity for distance and near without and with best
      correction, contrast sensitivity, patient satisfaction in 10-grade scale, degree
      of independence from glasses and frequency of lighting effects. RESULTS: After 6
      months from surgery uncorrected distance visual acuity > or =1.0 was achieved in
      55% of operated eyes (6/11), and the best corrected in 91% (10/11). Uncorrected
      near visual acuity in 2-6 months after surgery was achieved in all patients.
      Contrast sensitivity for spatial frequencies in the range 12 and 18cdg was
      decreased, but in 6 cdg was normalized after 6 months of observation, and in 3
      cdg was normal. Subjective patient satisfaction in 10-grade scale was on average
      in the first day after surgery 7.9 points and after 6 months 9.3. The necessity
      to use glasses (30%) and lighting effects had no bearing on subjective patient
      satisfaction perception. CONCLUSIONS: Multifocal diffractive lens implants are
      able to restore good visual acuity independent of distance and is effective and
      safe method in cataract surgery.

PMID- 17019993
TI  - Comparison of contrast sensitivity after implantation of diffractive lens SA60D3
      and monofocal lens MA60BM.
AB  - PURPOSE: Comparison of CSF in groups with diffractive lens SA60D3 and with
      monofocal lens MA60BM, and applying results to healthy population. MATERIAL AND
      METHODS: The study included 3 groups of patients. First group consisted of 10
      patients, who have undergone implant surgeries with diffractive lenses SA60D3 in
      both eyes; second group included 9 patients after implant surgeries with
      monofocal lenses MA60BM in both eyes. Third group included 10 patients with clear
      own lens. Groups were homogenous to number of patients, age and gender structure,
      as well as BCVA. CSF was determined for each eye. In the case of operated
      patients studies were performed 6 months after surgery. Homogeneity of groups was
      determined with Kruskal-Wallis test, but results of the studies were tested with
      variance. Results were shown in normalized CSF version. RESULTS: In conducted
      studies there was no statistical difference in specific evaluated cpd (3, 6, 12,
      18) between SA60D3 group and MA60BM group after 6 months from surgery (p = 0.892,
      p = 0.926, p = 0.564, p = 0.9953). The above results were obtained by testing
      variance at confidence level p < or = 0.01. At the higher confidence level p < or
      = 0.05 there was significant difference between SA60D3 group, MA60BM group and
      healthy control. CONCLUSIONS: Diffractive lenses SA60D3 decrease CSF in
      comparable range as monofocal MA60BM lenses, which does not change acceptable
      standard for quality vision for monofocal lenses, that is currently accepted.

PMID- 17019994
TI  - [Results of posterior lamellar keratoplasty].
AB  - PURPOSE: Posterior lamellar keratoplasty (PLK) in patients with pseudophakic
      corneal oedema. PARTICIPANTS AND METHODS: The PLK have been performed in our
      department since November 2004. The studied group consisted of 8 patients (7
      female and 1 male), 65 to 82 years of age (mean age: 71.5 years). Visual acuity
      before the surgery ranged from 0.01 to fingers counting. All the patients
      suffered from pseudophakic corneal oedema. Endothelial keratoplasty was performed
      using Melles technique: a deep stromal pocket was created across the cornea
      through a 5-mm scleral access incision. Endothelium was prepared from whole
      eyeballs collected according to the EEBA guidelines. Donor disc containing
      healthy endothelium was folded during the implantation procedure. Average donor
      endothelial cell density was 2800 cells/mm2. All surgeries were performed by one
      surgeon (EW). RESULTS: In two eyes conversion to PKP was necessary. Best
      corrected visual acuity (BCVA) ranged from 0.4 to 1.0 (mean 0.6 +/- 0.12).
      Postoperative astigmatism ranged from 0.75 to 2.5 D (mean 1.8 D +/- 0.34).
      Postoperative endothelial cell density ranged from 1700 do 2300 cells/mm2 (mean
      2200 cells/mm2 +/- 150). Mean Postoperative endothelial cell loss came to 29%.
      CONCLUSIONS: Posterior lamellar keratoplasty is a feasible surgery to manage
      corneal endothelial disorders. Automation of procedures by the use of laser
      preparation of donor tissue and adaptation automatic microkeratomes will increase
      the afterrepeating of procedures.

PMID- 17019995
TI  - [Bilateral Purtscher's retinopathy associated with acute pancreatitis--case
      report].
AB  - The project's aim is to report a case of Purtscher's retinopathy associated with
      acute pancreatitis. During the treatment gradual improvement of visual acuity and
      retina condition have been observed. In the report, the actual views on the
      pathogenesis of this disease have been discussed.

PMID- 17019996
TI  - [Bilateral optic nerve sheath meningioma (ONSM) --diagnostic and therapeutic
      problems].
AB  - The authors describe the case of bilateral optic nerve sheath meningioma /ONSM/
      in 14 years old girl. When being hospitalized at the Neurology Clinic with
      paresis n.VII, the patient was examined by ophthalmologist. The diagnosis was
      made on the basis of clinical and characteristic changes revealed by USG, CT and
      MRI. The very first ophthalmologic examination confirmed a visual acuity 5/5 OD
      and hand movements OS, associated with papilloedema OD and edematous optic
      atrophy OS. The use of USG, CT and MRI revealed bilateral tubular thickening of
      the optic nerves (8mm), with calcification. After the period of one year,
      clinical progression was observed. The intracranial tumor extended. It was shown
      in diagnostic imaging. The patient was operated on by neurosurgeons with
      histopathology verification. In the later stage she underwent radiotherapy. The
      case has been described because of its diagnostic and therapeutic difficulties.

PMID- 17019997
TI  - [Bronchial carcinoid--a rare neoplasm metastasis to choroid].
AB  - PURPOSE: To present a clinical picture and results of treatment in two patients
      with bronchial carcinoid metastases to choroid. MATERIAL AND METHODS: Two females
      aged 47 and 56 with bilateral and multiple metastases of bronchial carcinoid were
      enrolled in this study. Choroidal metastases occurred 6-7 years after primary
      tumors had been diagnosed. The follow-up period ranged from 2.5 to 5 years. In
      one patient teleradiotherapy of choroidal metastases was performed, while in a
      second case plaque therapy with 106 Ru and 125 I and a diode laser therapy were
      used. RESULTS: After therapy, one patient demonstrated partial regression of two
      choroidal metastases and total regression of one tumor, while the second one,
      showed total regression of all intraocular tumors. One patient developed
      irradiation neuropathy and retinopathy as a result of teleradiotherapy, which
      were the main cause of decreased visual acuity in her one eye. CONCLUSIONS:
      Regarding the good prognosis and potentially long survival of patients with
      bronchial carcinoid, prompt treatment of choroidal metastases is recommended.
      Applied method of therapy depends on tumor size, its localization and patient's
      general condition.

PMID- 17019998
TI  - [Photodynamic therapy of circumscribed choroidal hemangioma].
AB  - PURPOSE: To evaluate efficacy of photodynamic therapy (PDT) with verteporfin in
      treatment of posterior pole symptomatic circumscribed choroidal hemangiomas.
      MATERIAL AND METHODS: Four patients (3 men and 1 woman), 15-55 years old (mean
      age: 29 years) with circumscribed choroidal hemangiomas of the posterior pole,
      were examined. The hemangiomas localization were subfoveal in one patient,
      extrafoveal in 2 cases, and juxtapapillar in one case. The diagnosis of choroidal
      hemangioma was established on the base of clinical examination, A and B--scan
      ultrasound imaging, Doppler ultrasonography, fluorescein and indocyanine
      angiography results. Tumour thickness before treatment ranged from 2.3-3.6 mm
      (mean thickness: 2.8 mm). One course of PDT with verteporfin was performed in 3
      cases, while in one patient PDT was performed four times. RESULTS: In a follow-up
      period which range from 3 to 14 months (mean 5.7 months) all cases demonstrated
      clinical features of lesion regression with a reduction of thickness on
      ultrasonography and choroidal vasculature on angiograms. Visual acuity was
      improved in 3 patients (from 1 to 4 lines on Snellen charts), or remained stable
      in 1 case. CONCLUSIONS: Our preliminary results indicate that PDT with
      verteporfin is a safe and effective method of treatment for circumscribed
      choroidal hemangiomas, especially in patients with posterior pole location of the
      tumour.

PMID- 17019999
TI  - [Intraocular lens power calculation in patients after keratorefractive surgery-
      personal experience].
AB  - PURPOSE: To assess the efficacy of intraocular lens power calculation in patients
      with previous corneal refractive surgery. MATERIAL AND METHODS: Retrospective
      analysis of patients after laser refractive procedures, in whom cataract removal
      with phacoemulsification method was performed. Corneal power, which in
      conventional measurements after refractive surgery tends to increase value and
      results in postoperative hyperopic shift, were calculated with five methods, and
      the results were compared. To asses IOL power SRK/T formula was used. RESULTS:
      Mean spherical equivalent three months after procedures according to target
      refraction in examined patients ranged from -1.00 to +1.75 D. The difference
      between obtained and target refraction in 55% of patients ranged from -0.50 to
      +0.50, and in 77% from -0.75D to +0.75D. Best results were obtained in
      calculations performed with Rossa method. The least effective appeared to be
      traditional IOL power calculation method without correcting factors. CONCLUSIONS:
      In patients after laser correction of myopia, value of the measured keratometry
      should always be corrected. The most effective is Rosa method in combination with
      SRK/T calculation algorithm.

PMID- 17020000
TI  - Tick inoculation in an eyelid region: report on five cases with one complication
      of the orbital myositis associated with Lyme borreliosis.
AB  - PURPOSE: To determine the frequency and dependence of Lyme borreliosis after tick
      infestation in the eyelid region. MATERIAL AND METHODS: Five patients after tick
      inoculation were investigated by immunofluorescence assays for IgM and IgG
      system). Ophthalmologic evaluation of myositis was supported with MRI,
      laboratory, and internal clinical investigations. RESULTS: Four children showed
      negative Borrelia serology after a bite from a tick. In one case the left
      abducens nerve palsy was found, which was diagnosed in MRI as a thickened left
      lateral rectus muscle. The diagnosis of myositis with positive Borrelia
      burgdorferi serology was consistent with Lyme borreliosis. Other laboratory
      examinations were negative. The symptoms were reduced after treatment with
      ceftriaxon. CONCLUSIONS: Lyme borreliosis was found in one in five patients after
      tick infestation in the eyelid region. Antibiotic prophylaxis against Lyme
      borreliosis with ampicillin is recommended for children after a tick bite.

PMID- 17020001
TI  - [Persistent hyperplastic primary vitreous--developmental anomaly of the eye in
      children].
AB  - Persistent hyperplastic primary vitreus in children continues to be a diagnostic
      and therapeutic challenge for ophthalmologists. It can occur in isolation, in
      association with other ocular disorders and rarely as a part of systemic
      disorder. Characteristic features include microphthalmic eye, white vascularized
      retrolental tissue with or without a persistent hyaloid artery, centrally dragged
      ciliary processes, an anteriorly shifted and (or) swollen lens, and varing
      degrees of lenticular opacification. PHPF is the most common associaton with
      unilateral cataracts. Differential diagnosis and functional effect of treatment
      are discussed.

PMID- 17020002
TI  - [The place of filtration surgery in the treatment of adult onsets of primary
      glaucoma].
AB  - The author presents contemporary opinion on the place of filtration surgery in
      the treatment of adult onsets of primary glaucoma. Increasing age and greater IOP
      fluctuation increase the odds of VF progression after surgical intervention.
      Retinal ganglion cell function, optic disc morphology as well as VF parameters,
      can be at least partially restored after surgical IOP reduction in early
      glaucoma. It is the most important, to choose the critical time for surgical
      intervention in the aim to achieve reversal of field loss.

PMID- 17020003
TI  - [A new approach towards giant cell arteritis].
AB  - Giant cell arteritis is a rare systemic vasculitis affecting large- and medium
      sized arteries. Focal arteries lesions, include mononuclear cells infiltration of
      the vessel wall with giant cell formation. It is a disease of elderly persons and
      can result in a wide variety of systemic, neurological and ophthalmic
      complications, due to ischemia. The incidence of visual loss and ocular
      involvement varies between 14-88%, but one of the most common and severe
      complications is anterior ischemic optic neuropathy. The other ocular ischemic
      lesions include: central retinal artery occlusion, choroidal ischemia, diplopia,
      ocular motor paresis, anterior uveitis, cataract, ocular hypotony, corneal oedema
      and ulcerations, episcleritis and anterior scleritis, orbital cellulitis and
      pseudotumor. Because giant cell arteritis is potentially blinding disease, early
      diagnosis and immediate treatment with high dose corticosteroids may prevent
      further damage to the affected eye and prevent visual loss in the opposite eye.
      The purpose of this review is to revise established knowledge and to highlight
      the recent developments in diagnosis and management of giant cell arteritis.

PMID- 17020004
TI  - [Ischemic optic neuropathy. Pathogenesis, clinical features, diagnostics and
      treatment].
AB  - Ischemic optic neuropathy is a common cause of visual loss in the older
      population. This disease is classified into anterior and posterior type according
      to the location the lesions. The anterior type is due to transient nonperfusion
      or hypoperfusion of the ciliary circulation in the optic nerve head. The etiology
      of this disease is multifactorial. The most important risk factors for developing
      anterior ischemic optic neuropathy (AION) include hypertension, nocturnal
      hypotension, diabetes mellitus, atherosclerosis and small cup in the optic disc.
      AION presents with sudden painless loss of vision, pale edema of the optic disc,
      afferent papillary defect and visual field defects, typically in lower quadrants.
      Posterior ischemic optic neuropathy (PION) is a rare condition and diagnosis of
      it usually is made only after other causes of a retrobulbar optic neuropathy have
      been excluded. There are three distinct subtype of PION: perioperative, arteritic
      and nonarteritic. They are characterized by acute visual loss, variable visual
      field defects, relative afferent pupillary defect and normal optic disc.

PMID- 17020006
TI  - [Multifocal intraocular lenses].
AB  - Multifocal intraocular lenses are the new option not only in cataract surgery,
      but either in refractive surgery. Use of multifocal lenses make patients less
      dependent on spectacle, than after implantation of monofocal intraocular lenses.
      In this article we present an actual review of multifocal intraocular lenses. Two
      main types of the implants: refractive and diffractive are described with their
      detailed characteristics. Special attention we paid on advantages and
      disadvantages as well as some limits to implantation of the multifocal implants.

PMID- 17020005
TI  - [Anatomical and physiological essentials of the blood supply of the optic nerve].
AB  - Ischemic disorders of the optic nerve constitute an important cause of visual
      loss. Therefore, to understand the pathogenesis of these diseases, it is
      imperative to be familiar with the vascular anatomy and physiology of the optic
      nerve. The purpose of this paper is to present a brief overview of the current
      state of knowledge on this topic. The blood supply of four anatomical regions of
      the optic nerve, factors influencing the optic nerve circulation and
      autoregulation mechanism are presented.

PMID- 17020007
TI  - [Retinoblastoma update--management and classification (Part I)].
AB  - The aim of this paper is to present updated data on diagnosis, management and
      classification of retinoblastoma. The authors describe the growth patterns of
      retinoblastoma including the diffuse infiltrating type, the features of
      sponatneously regressed and sponatneously arrested retinoblastoma. In addition,
      retinoblastoma genetics including 13 q deletion syndrome, are discussed. Finally,
      they present the International Intraocular Retinoblastoma Classification (IIRC)
      and make recommendations regarding chemotherapy after enucleation based on
      histopathology findings.

PMID- 17020008
TI  - [Retinoblastoma update--therapy (Part II)].
AB  - The aim of this paper is to present updated data on the treatment of
      retinoblastoma. The authors describe current management based on the
      International Intraocular Retinoblastoma Classification (IIRC). They discuss the
      different methods of treatment, including chemoreduction, subconjunctival
      carboplatin, transpupillar thermotherapy, cryotherapy, laser photocoagulation,
      episcleral plaque radiotherapy, external-beem radiotherapy and enucleation.

PMID- 17020009
TI  - Concentrations of carnosine, anserine, L-histidine and 3-methyl histidine in boar
      spermatozoa and sheep milk by a modified HPLC method.
AB  - The present study deals with the application of high-performance-liquid
      chromatography (HPLC) method for a quantitative detection of carnosine, anserine,
      L-histidine and 3-methyl-L-histidine in biological material with o
      phthaldialdehyde (OPA) post column derivatisation at the constant temperature of
      50 degrees C. For this purpose, some mobile-phases were prepared with scalar
      acetonitrile concentrations. A complete separation of all molecules, particularly
      for carnosine and 3-methyl-L-histidine, was obtained with a solution of
      acetonitrile and 6mM hydrochloric acid with 0.48 M sodium chloride (5%:95% v/v).
      Post column derivatisation reaction at temperature of 50'C permitted to obtain an
      increase in sensibility of all molecules. This method has been utilised for
      detection of histidine dipeptides in boar spermatozoa and in sheep milk.
      Concentrations (mean +/- S.E. nmol/10(9) spermatozoa) of carnosine (0.96 +/-
      0.14) and anserine (0.83 +/- 0.18) in boar spermatozoa were significantly lower
      than those of L-histidine (52.85 +/- 4.86) and 3-methyl-L-histidine (83.07 +/-
      7.1). Positive correlation was found between carnosine and anserine contents (r =
      0.740; p < 0.01) and between L-histidine and 3-methyl-L-histidine (r = 0.657; p <
      0.01). All histidine dipeptides studied were also present in 40 samples of sheep
      milk. In a case of samples without unit-forming colonies (UFC) of Staphylococcus
      coagulase-positive, carnosine concentrations (9.17 +/- 0.89 nmol/ml) were higher
      than anserine (0.51 +/- 0.02 nmol/ml) and both were significantly lower in
      respect to L-histidine (49.51 +/- 6.48 nmol/ml) and 3-metyl-L-histidine (81.21 +/
      6.82 nmol/ml). A negative correlation was observed between carnosine milk levels
      (r = -0.773; p < 0.01) and UFC/ml of Staphylococcus coagulase-positive. In
      conclusion this very simple and fast method can be used to detect histidine
      dipeptides in biological compartments where their concentrations are very low.

PMID- 17020010
TI  - Epidermal growth factor and epidermal growth factor receptor immunoreactivity in
      the endothelial cells of the uterine artery and its branches during different
      stages of the estrous cycle in the pig.
AB  - The uterine artery and its branches are the most important vessels that supply
      the uterus with blood, nutrients and active substances. Epidermal growth factor
      (EGF) and its receptor (EGFR) are expressed in many tissues, including
      reproductive organs, and is involved in angiogenesis, embryo implantation and
      development as well as in proliferation and differentiation of various cells. The
      aim of our study was to determine EGF and EGFR immunoexpression in the uterine
      artery and its branches during the estrous cycle in the pig. The experiment was
      performed on cryostat sections of the uterine artery and its branches stained
      immunohistochemically by ABC method. Light microscopic observations revealed the
      phase-related immunoreactivity of EGF and EGFR in the endothelial cells of the
      uterine artery and its branches. The highest intensity of EGF and EGFR
      immunoreaction in endothelial cells of the uterine artery was observed in the
      follicular phase. A significant decrease in the intensity of EGF and EGFR
      immunoreactivity was found in the middle luteal phase. Similar results of the
      immunostaining were found with regard to EGFR. In the endothelium of the uterine
      arterial branches, a significant increase in the intensity of EGF and EGFR
      immunoreactivity was observed in the middle luteal phase. A decrease in the
      intensity of EGF immunostaining was observed in the late luteal phase. The phase
      related expression of EGF and EGFR in the endothelium of the uterine artery and
      its branches suggest the modulatory effect of EGF and its receptor on the uterine
      artery and the region supplying these vessels.

PMID- 17020011
TI  - Immunoreactivity of c-Fos, NGF and its receptor TrkA in the periventricular zone
      of the rat hypothalamus after open field exposure.
AB  - The immunoreactivity (ir) for c-Fos, NGF and TrkA, following an acute and chronic
      open field stress, were studied in the periventricular zone of rat hypothalamus.
      Adult rats were divided into three groups: control, exposed to acute (single
      exposure--15 minutes) and chronic (multiple exposures--15 minutes daily for 21
      days) open field stress. In the control rats neurons immunoreactive to c-Fos,
      TrkA and NGF were found. The number of TrkA- and NGF-ir cells was high, whereas
      this of c-Fos-ir ones was low. In animals exposed to acute open field stress the
      number of c-Fos-ir cells in the examined nuclei varied, however it was much
      higher than that in the control animals. The number of TrkA-ir neurons in all the
      studied nuclei was also higher than that in the control animals, but the increase
      of the number of NGF-ir neurons was not observed in supraoptic nucleus. In the
      animals exposed to chronic open field stress the number of c-Fos-ir cells was
      increased in comparison to that in the control rats. After chronic stress
      exposure the number of TrkA-ir neurons in supraoptic nucleus remained high in
      comparison to that in animals exposed to acute stress, whereas it was decreased
      in other studied nuclei. No significant differences in the number of NGF-ir cells
      were observed between the groups exposed to the acute and chronic stress.
      Observed decrease of c-Fos- and TrkA-ir in the studied nuclei in the animals
      suffering from chronic stress in comparison with the acute one may indicate the
      occurrence of habituation phenomenon. This phenomenon does not concern NGF-ir.

PMID- 17020012
TI  - Yeasts and algae isolated from cows with mastitis in the south-eastern part of
      Poland.
AB  - The aim of the study was to evaluate the occurrence of mycotic and protohecal
      mastitis in herds in south-eastern part of Poland. A total of 3091 milk samples
      from udder quarters with clinical and subclinical mastitis from 29 dairy herds
      was investigated in this survey. Milk samples were plated as soon as possible on
      blood agar (BA), Mac Conkey agar, aesculin-tallium acetate-crystal violet agar,
      and Sabouraud agar. A hundred and thirty one yeast (4.23%) and eleven Protoheca
      zopfii (0.35%) strains were isolated from cows with clinical and subclinical
      mastitis. All the isolated fungi were the yeast classified into 4 genera
      (Candida, Trichosporon, Saccharomyces and Rhodotorula). The most frequently
      isolated yeasts were Candida sp., C. kefyr, C. humicola, C. rugosa and C.
      inconspicua. Both fungi and algae were isolated first of all during a confinement
      housing season.

PMID- 17020014
TI  - Etiological agents of dairy cows' mastitis in western part of Poland.
AB  - The purpose of the study was to determine the etiological mastitis agents in cows
      from herds located in the western part of Poland in years 2003-2005.
      Bacteriological examinations of 18,713 samples taken from California Mastitis
      Test (CMT) positive quarters were performed according to standard methods. Some
      Gram-negative bacilli and Gram-positive cocci were examined with the use of API
      tests (Analytical Profile Index). It was found that 32.7% of samples that were
      CMT positive were culture negative and 9.3% of samples were contaminated.
      Streptococcus species (15.7%), coagulase negative staphylococci (CNS) (14.6%),
      Staph. aureus (8.6%), Gram-negative bacilli (4.0%) and Corynebacterium species
      (3.8%) were most frequently isolated. Escherichia coli (52.3%) dominated among
      Gram-negative bacilli followed by Klebsiella pneumoniae (4.1%), Pseudomonas
      aeruginosa (3.6%), Enterobacter cloacae (3.6%), Serratia marcescens (3.1%),
      Pasteurella multocida (3.1%), Acinetobacter lwofii (3.1%), and 26 other bacteria
      species. Stahylococcus xylosus (31.5%), Staph. hyicus (12.2%), Staph.
      haemolyticus (12.2%), Staph. sciuri (11.6%), Staph. chromogenes (8.8%), Staph.
      epidermidis (8.3%) and Staph. simulans (6.1%) were the most frequent CNS.
      Streptococcus uberis (50%), Str. dysgalactiae (19.7%), Str. acidominimus (6.6%)
      and Enterococcus faecalis (5.3%) were mostly found among CAMP-negative
      streptococci. An increase in frequency of mastitis caused by non-agalactiae
      streptococci, Staph. aureus, A. pyogenes and yeast-like fungi and a decrease in
      that produced by Str. agalactiae in 2005 as compared to years 2003 or 2004 were
      observed.

PMID- 17020013
TI  - Influence of folic acid, vitamin B2 and B6 supplementation on feed intake, body
      and organs weight, and liver fatty acids composition in rats subjected to severe
      protein deprivation.
AB  - Growing rats fed for 3 months a low-protein (LP) diet (4.5% of energy from
      protein), possessed about 29% lower body weight than animals consuming adequate
      protein diet (20% energy from protein). The LP diet feeding caused an increase in
      daily feed intake followed by a decrease in feed conversion efficiency. The
      enrichment of LP diet with folic acid, vitamin B2 and B6 (3 times above the level
      applied in the control diet) did not have any impact on rats BW and
      supplementation with these vitamins minimize the effect of LP diet on feed
      intake. The use of examined vitamins had a tendency to diminish an increase in
      feed conversion ratio caused by the LP nutrition. This effect was significant
      when all vitamins were added together. Rats fed the LP diet had higher relative
      weights of lungs, heart, liver and testis. Vitamins enriching the LP diet were
      observed to decrease a relative weight of lungs (folic acid, vitamin B6 and
      vitamin mixture), and liver (vitamin B6 and vitamin mixture). A tendency of
      increasing relative testis weight was also revealed in rats given the LP diet
      enriched with vitamins. The lower content of hepatic polyunsaturated fatty acids
      (FA) and a tendency for monounsaturated FA content to be higher were found in
      rats fed the LP diet. The LP diet enrichment with folic acid caused that these
      changes were more pronounced and statistically significant. Enrichment of LP diet
      with vitamins tested may cause a partial reverse of changes observed in the
      hepatic FA composition.

PMID- 17020015
TI  - The influence of medium on viability of bovine morulae produced in vitro after
      their biopsy.
AB  - The aim of this study was to determine the influence of two different media on
      the viability of in vitro produced biopsied bovine morulae. Bovine morulae were
      produced in vitro, then biopsied and cultured in the Ham's F10 and IVM media.
      Cultured and control morulae were stained with Hoechst 33342 and propidium
      iodide. Morulae were classified morphologically for excellent, good and
      degenerated quality. 42.86% of biopsied morulae cultured in the Ham's F10 medium
      and only 11.11% (only one) of these embryos cultured in the IVM were of excellent
      quality. Embryos of good quality were about 2 times less numerous in Ham's F10
      medium (28.57%) than in IVM medium (55.5%) (P < or = 0.05). 28.57% of biopsied
      morulae cultured in Ham's F10 medium and 33.33% of these embryos cultured in the
      IVM degenerated (P > or = 0.05). The media had no significant influence on the
      number of total and viable blastomeres of morulae cultured in vitro after biopsy
      (P > or = 0.05). But the quantity of restored (excellent and good quality)
      embryos was higher when they were cultured after biopsy in Ham's F10 medium than
      in IVM. These statistically significant results (P < or = 0.05) show that the
      Ham's F10 medium is better for the restoring of biopsied bovine embryos produced
      in vitro than IVM.

PMID- 17020016
TI  - Treatment of fractured antebrachial bones in both thoracic extremities in toy
      breed dogs by application of reconstruction plates.
AB  - Stabilization of fractures at distal third of antebrachial bones in toy breed
      dogs is often connected with bone healing complications, including delayed union
      or non-union. In the present study 9 toy breed dogs with fractures at distal
      third of the epiphysis of two antebrachial bones were treated. Each dog had
      fractured both thoracic limbs. In all the dogs, internal stabilization was
      applied using the 1 mm, 4 or 5 -hole reconstructive mini plates. In three dogs
      mini plates were applied in treatment of non-union of antebrachial bones. In each
      case radius bone was stabilized only. X-ray examination performed in all the dogs
      10 weeks postoperatively showed complete adhesion of treated bones. It was found
      that application of reconstructive mini plates in treatment of simultaneous
      fractures of distal shaft of both antebrachial bones is effective therapeutic
      method.

PMID- 17020017
TI  - [Study on in-plane optical anisotropy of semiconductor materials by reflectance
      difference spectroscopy].
AB  - In the present review, the measuring principle of reflectance difference
      spectroscopy (RDS) is given. As a powerful tool in the surface and interface
      analysis technologies, the application of RDS to the research on semiconductor
      materials is summarized along with the origins of the in-plane optical anisotropy
      of semiconductors. And it is believed that RDS will play an important role in the
      electrooptic modification of Si-based semiconductor materials.

PMID- 17020018
TI  - [Second-harmonic detection with tunable diode laser absorption spectroscopy of CO
      and CO2 at 1.58 microm].
AB  - Tunable diode laser absorption spectroscopy has been applied in the fields of
      atmospheric chemistry and monitoring pollutant gases as a new method of measuring
      trace gases. The technique of remote sensing of CO and CO2 at 760 mm Hg pressure
      with tunable diode laser absorption spectroscopy in the near-infrared region is
      introduced. And the relationship between the second-harmonic spectrum of CO2 in
      Lorentzian line shape and the modulation amplitude is also presented.

PMID- 17020019
TI  - [VUV excited luminescence of LnZr(BO3)2 : Eu3+ (Ln = Ba, Sr)].
AB  - Powder samples of Ba(1-x) Sr(x)Zr(BO3)2 : Eu3+ (0 < or = x < or = 1) were
      prepared by the conventional solid state reaction method. The excitation spectrum
      shows a strong absorption in the VUV region with the broad absorption band edge
      at 130-170 nm due to the host and the f --> d transition of Eu3+, and another
      absorption band of charge-transfer state (CTS) of Eu3+ in the region of 230 nm.
      The absorption of the charge-transfer band of Eu3+ can be increased by
      incorporating Al3+ ion into Zr4+ ion lattice. The luminescence of Ba(1-x)
      Sr(x)Zr(BO3)2 : Eu3+ is also increased by incorporating Al3+ into the lattices.
      In Ba(1-x) Sr(x)Zr (BO3)2 : Eu3+, the intensity of the absorption band (130-170
      nm) decreases, and the band shifts about 30 nm toward lower energy with x
      increasing. The emission spectra revealed an intense and sharp (616 nm) red color
      emission from Eu3+ (5 Do --> F2) transition under 147 nm VUV excitation.

PMID- 17020020
TI  - [The electroluminescence of a novel complex Eu(o-BBA)3(phen)].
AB  - A novel rare earth complex of Eu ion with 2-benzoylbenzoic acid and 1,10
      phenathrolinephen (Eu(o-BBA)3 (phen)) was synthesized and used as a dopant to
      fabricate efficient electroluminescence(EL) devices. It was doped into poly(N
      vinylcarbazole) (PVK) and spin coated into films. Devices using organic layer
      Alq3 (or inserted hole blocking layer BCP) and inorganic layer ZnS as electron
      transporting layer respectively were fabricated. The luminescence properties of
      the single-layer decvice A (ITO/PVK : Eu/Al) and the organic-inorganic
      heterostructure device were analyzed. It was found that the device using ZnS as
      the electron transporting layer has higher brightness and lower threshold voltage
      while maintains pure emission.

PMID- 17020021
TI  - [Synthesis and photoluminescence of N-benzoin aniline, 1,10-phenanthroline, and
      europium ternary complex].
AB  - New N-benzoin aniline and Eu(BZA)3 phen were synthesized, and they were
      characterized by EA, IR, 1H NMR and UV. The Eu(III) complex spectra were excited
      at the wavelength of 342 nm, which exhibited a red emissive color, and the Eu
      characteristic peaks appeared at 592 and 615 nm, respectively. The 615 nm
      transition showed the strongest emission. N-benzoin aniline sensitizes to Eu ions
      and it is a good ligand of Eu complex.

PMID- 17020022
TI  - [Study on photo-degradation kinetics of hemin in the presence of anion
      surfactant].
AB  - A novel photodecomposition behavior of hemin was described. With RhB-H2O2 system
      a flow injection chemiluminescence method has been applied to the study of the
      photolytic kinetics of hemin under ultraviolet light. And the sodium dodecyl
      sulfonate (SDS) was added as a photostability-stabilizer. The results showed that
      the decomposition reaction of hemin in the presence and absence of SDS
      corresponded to a first-order reaction. Furthermore, the presence of SDS in the
      system decreased the photolytic rate of hemin by 1.8 times compared to that in
      the absence of SDS.

PMID- 17020023
TI  - [FTIR characterization of the secondary structure of a staphylokinase variant
      (K35R) encapsulated within PLGA microspheres].
AB  - The secondary structure of a staphylokinase variant (K35R, DGR) encapsulated in
      poly (lactic-co-glycolic acid) (PLGA) microspheres was quantitatively examined by
      Fourier transform infrared (FTIR) spectroscopy. Resolution enhancement technique
      and Fourier deconvolution were combined with band with curve-fitting procedures
      to quantitate the spectral information from the amide I bands. Nine component
      bands were found under the broad, nearly featureless amide I bands and assigned
      to alpha-helix, beta-sheet, turn and irregular (random) structures. The changes
      of bands at 1 651 and 1 623 cm(-1) after encapsulation were discussed.

PMID- 17020024
TI  - [Application of MALT-CLS method to FTIR quantitative analysis of atmospheric
      trace gas].
AB  - The MALT-CLS method for quantitative analysis of atmosphere trace gas by FTIR
      spectrometry was studied. Some experiments are described, such as long-path White
      cell, and passive remote sensing of aircraft. The characteristic of this method
      is that the calibration spectra are calculated from a database of absorption line
      parameters HITRAN using MALT program, including environmental and instrumental
      effects in the calculation. It is particularly useful in long open-path and solar
      FTIR spectroscopy, or passive remote sensing by FTIR.

PMID- 17020025
TI  - [Study on N-acetylated chitosans by FTIR and XRD].
AB  - The degree of N-deacetylation (DD) is an important property of chitosan. In the
      present article the reaction of N-acetylation was applied to prepare six chitosan
      samples with various DDs. The samples were studied by FTIR and XRD to investigate
      their IR absorbance characteristics and crystallinity, from which the DDs and
      crystallinity index (CrI) of chitosans were also determined respectively. The
      influence of N-acetylation on DD and CrI was also discussed, and it could be
      found from FTIR that the N-acetylation reaction became difficult for the
      remaining amino group in chitosan molecule as the reaction proceeded. XRD also
      indicated that the crystalline zone was broken by N-acetylation gradually, and
      another kind of crystal form appeared instead.

PMID- 17020026
TI  - [FTIR research on the modification of plant oil pitch binders by polyester
      waste].
AB  - Various plant oil pitchs (cottonseed pitch, bean oil pitch, and mixed plant oil
      pitch) were used to prepare the plant oil pitch binders for casting. They were
      treated by polyester waste and processed by several technics such as esterifying.
      In the mean time, FTIR and TG were adopted to learn the structure, property, and
      sclerous mechanism of the binders. From the comparison with synthetic fat binder,
      the authors can see that the treated binders have similar components. They also
      have many excellent properties such as higher dry tensile strength and slower
      deflation velocity, which equal to or even exceed the properties of synthetic fat
      binder. Therefore, the treated binders, which were cheaper, can be used to make
      class I mold and core binders.

PMID- 17020027
TI  - [FTIR study of nano-iron oxyhydroxides' decoloration on the azo dye].
AB  - IR spectra were used to analyse the azo dye solution decoloration action by two
      kinds of iron oxyhydroxides. It was discovered that: (1) Acid Red G and methyl
      orange are apt to form complex on the surface of iron oxyhydroxides > FeOH,
      especially Acid Red G. which possesses two -SO3Na structures has a relatively
      high decoloration efficiency as a result of complexation reaction; (2) after 2
      hours adsorption, the IR spectra of iron oxyhydroxides show characteristic wave
      numbers at 1 033 and 1 030 cm(-1) which belong to -SO3Na, whereas the peaks at
      wave numbers between 1 450 and 1 400 cm(-1), which belong to azo dye, disappear.
      These phenomena indicate that azo dye molecules are adsorbed on the surface of
      iron oxyhydroxides due to the negative -SO3Na structure, and at the moment azo
      dye molecules are adsorbed on the surface of iron oxyhydroxides, the electron
      transfer occurs between the azo dye molecules and the iron oxyhydroxides
      surface's Fe3+ centre, which could lead to the rupture of azo bond. It can be
      infered that the decoloration of azo dye molecules is the co-effect of the
      selective chemical absorption and the oxidation-deoxidation effect on the surface
      of iron oxyhydroxides.

PMID- 17020028
TI  - [The analysis of wood microfibril angle by near infrared spectroscopy and X-ray
      diffractometry].
AB  - In the present paper, near infrared (NIR) spectroscopy and X-ray diffractometry
      were used to rapidly predict the microfibril angle (MFA). MFA is one of the most
      important factors affecting wood properties. Wood resource utilization and tree
      improvement programs require cost-effective methods for the rapid analysis of
      thousands of samples. In the experiment, the average MFA of each sample were
      rapidly measured by X-ray scanning diffractometry. Then, the PLS model was built
      between NIR data and MFA by the X-ray measured. As a result, a very strong linear
      relationship has been found between NIR spectra fitted and X-ray measured, and
      the coefficients (r2) of calibration and prediction models were 0.867 and 0.816
      respectively.

PMID- 17020029
TI  - [Detection of tofu hardness by near infrared spectroscopy].
AB  - The possibility of determination of tofu hardness by near infrared spectroscopy
      (NIR, 833-2500 nm) was studied. The influences of water content and protein
      content on the spectra were discussed, in order to detect the hardness. The
      models of Tofu hardness were calibrated by partial least squares regression (PLS)
      after eliminating outline, spectra pretreatment, and wavelength optimization (r =
      0.994, RMSEC = 0.391%, RMSEP = 0.416%, RSD = 2.27%). All of the results were
      better than those by sense assessing method.

PMID- 17020030
TI  - [Study on the identification of standard and false Gancao by Fourier transform
      infrared spectroscopy].
AB  - Standard Gancao (Glycyrrhiza uralensis Fisch) and false Ciguogancao (Glycyrrhiza
      pallidiflata Batal) were identified fast, nondestructively by Fourier transform
      infrared spectroscopy (FTIR) combined with derivative spectra and two-dimensional
      correlation spectroscopy (2D) in the present article. The result shows that
      although the two kinds of Gancao belong to one genus, there are some certain
      differences in their chemical components that are reflected in the IR spectra,
      but with some similarity and dissimilarity in the IR spectra. The two kinds of
      Gancao are quite different from each other in second derivative spectra and 2D
      spectra. Based on the differences reflected in the IR and 2D IR, the standard
      gancao can be identified from the false easily and clearly. The result also
      proved that there is a relationship between the IR spectra and the chemical
      components of the herbs. This method is fast, accurate and nondestructive, and
      the wastage of sample is less. The fast, accurate property of 2D spectroscopy
      makes it a powerful and new approach to evaluating medicinal herbs impersonally.

PMID- 17020032
TI  - [Analysis of modifying polymer in the modified asphaltum waterproof membrane].
AB  - The waterproof roller sheet of modified asphaltum is extensively used in many
      waterproof constructions. The modified asphaltum by polymer is of good
      performance, such as cold-resistant, high intension etc. In the present paper,
      the modifying polymer was seperated from the waterproof membrane of modified
      asphaltum. The structure of the modifying polymer was identified by IR, 13C NMR,
      and Py-GC/MS. The results show that the polymers are SBS and polyisobutylene.

PMID- 17020031
TI  - [Analysis and discrimination of Collocalia esculenta L. via FTIR spectroscopy].
AB  - Collocalia esculenta L. is called Yanwo in China. Thirty kinds of dry yanwo were
      identified by Fourier transform infrared spectroscopy (FTIR) . The results
      indicated that there were some obvious differences in FTIR between the dry yanwo
      and the natural yanwo, mainly represented in some absorption peaks of protein,
      amino acid (1 634, 1 535 cm(-1)) and amylase (1 034 cm9-1)). Meanwhile, the
      shape, position and intensity of the peaks from methylene (2 935 cm(-1)), protein
      and amino acid (1 647, 1 533, 1 447 cm(-1)) in dry yanwo were similar to those of
      the glutin. Therefore, different amounts of glutin were added in dry yanwo
      samples. The content of candy in some dry candy yanwo products was as high as
      99%, but the content of yanwo was only 1%. The characteristic peaks of yanwo in
      these products even could not be found. So the quality of yanwo in the market
      could not be guaranteed from these results. FTIR is fast and direct to analyse
      and evaluate the quality of yanwo product.

PMID- 17020033
TI  - [Method for retrieving pollution gas concentration from Raman lidar return].
AB  - Raman lidar is an important tool for the detection of atmosphere pollution, and
      inversion for lidar returns is an important process. The key for inversion is to
      get transmission exponential function exp [integral of 0 (R) [alpha(lambda1, z) -
      alpha(lambda2, z)]]. Three methods with extinction coefficient as the center are
      presented. First, 532 nm atmospheric extinction coefficient was used to
      indirectly obtain alpha(lambda1, z) and alpha(lambda2, z). This method has been
      used generally by people. Two new methods were proposed: 1, reference gas with
      approximate Raman wavelength is used so that alpha(lambda1, z) = alpha(lambda2,
      z). 2, Mie-Rayleigh scattered return with wavelength lambda1 or lambda2 is used
      to compute exp [integral of 0 (R) [alpha(lambda1, z) - alpha(lambda2, z)]].

PMID- 17020034
TI  - [Application of near-field Raman spectroscopy to nano-structure
      characterization].
AB  - Near-field Raman spectroscopy is a novel technology in the near-field optics, and
      attracts much attention of scientists because of the realization of spectral
      characterization of nano-structure. The technical advantage of Raman spectroscopy
      is described in the present review. The principle and practical technical scheme
      of near-field Raman spectroscopy systems are introduced. Several applications of
      near-field Raman spectroscopy are mentioned in detail, including carbon nanotube
      characterization, biological specimen imaging, thermoelectric crystal
      characterization, dye single molecule detection etc., revealing a broad prospect
      of the development of near-field Raman spectroscopy in various scientific
      research fields.

PMID- 17020035
TI  - [Application of p-aminothiophenol as a SERS reporter in immunoassay].
AB  - The adsorption of p-aminothiophenol (PATP) molecule on the gold electrode was
      investigated. The result suggests that PATP was adsorbed perpendicularly onto the
      substrate. By immobilizing goat anti-mouse IgG on a glass slide modified by
      special organic molecules, the antibody/antigen/reporter-labeled immunogold
      nanoparticle sandwich assay was build for surface-enhanced Raman spectroscopy
      (SERS) measurements. The p-aminothiophenol (PATP) was used as SERS-reporter
      molecule. Thus the authors can identify the single type biospecific species by
      SERS signal of the reporter molecules which are coimmobilized with antibody
      molecules in gold colloids.

PMID- 17020036
TI  - [Studies of laser Raman spectra of sodium glutamic acid solution effected with
      environmental light].
AB  - The laser Raman spectra influenced by environmental light have been studied in
      the determination of sodium glutamic acid solution. The environmental light
      included natural light from outdoors and the light from indoor fluorescents. The
      results show that different influences on laser Raman spectra of sodium glutamic
      acid solution can be produced in different environmental light. There were some
      characteristic spectral lines, minus peaks or sharpened peaks. These influences
      cannot be ignored. The determinations of laser Raman spectra must be performed in
      darkroom or in the sheathing or mantle etc.

PMID- 17020037
TI  - [Study the Raman spectroscopy of breast tumor limbic tissue].
AB  - The confocal Raman micro-spectra of breast tumor limbic fat tissues of forty
      cases after surgery were collected. Substantial differences were found among
      breast infiltrative ductal carcinoma, hyperplasia and fibroadenoma, which is
      possibly to be used as a character of breast cancer and other breast tumor and
      offers the evidence for the breast tumor diagnosis. So, the Raman spectroscopy of
      the breast limbic fat tissue is of great value.

PMID- 17020038
TI  - [Studies of relationships between Cu pollution and spectral characteristics of
      TritiZnm aestivum L].
AB  - The effect of Cu pollution on the Cu uptake by wheat, the characteristics of
      chlorophyll concentration, and the visible-near infrared spectra were studied
      under the condition of solution culture, and the relationships among the three
      indices were discussed. The results indicate that the content of Cu in TritiZnm
      aestivum L. increases and the concentration of chlorophyll reduces with the
      increase of Cu in solution. The spectral characteristics also take on the
      disciplinary diversification (the spectral reflectivity ascended in the visible
      light band and decreased in the near infrared band; the range of red edge shift
      decreased) with the increase of Cu in solution.

PMID- 17020039
TI  - [Syntheses and spectral characterization of low-molecular-weight chitosan-Ce(III)
      complexes].
AB  - The low-molecular-weight chitosan-Ce(III) complexes were synthesized at pH value
      1-2 and characterized by UV spectrum, fluorescence spectrum, FTIR spectrum and 1H
      NMR spectrum. Its coordination mechanism was also investigated. The results
      showed that Ce(III) was coordinated with -OH group instead of -NH2 group of low
      molecular-weight chitosan.

PMID- 17020040
TI  - [Research of Hg2+ sol-gel membrane made of organically modified silicates].
AB  - A photochemical sensor for the determination of Hg2+ consisting of organically
      modified silicates (ormosils) was developed. Hg(2+)-sensitive fluorescent sol-gel
      films were prepared by co-condensation of tetramethoxysilane (TMOS) and
      dimethyldimethoxysilane (DMOS), and the fluorescent indicator 5,10,15, 20-tetra
      (p-sulfonatophenyl) porphyrin sodium was embedded in sol-gel in the form of ion
      pairs with cetyltrimethyl ammonium bromide. The optimization condition of
      preparation and response performance of sol-gel membrane were investigated. The
      experimental results showed a linear range of Hg2+ concentrations from 1.0 x 10(
      5) to 1.0 x 10(-4) mol x L(-1) in a Tris-HCl buffer at pH 8.0 with fast response
      and good repetition. The indicators in the sol-gel membrane did not leak out and
      the sensor showed good selectivity over other metal ions.

PMID- 17020041
TI  - [Study on the characterization of beta-cyclodextrin-diferrocenylenone inclusion
      complex and micro-environmental effects].
AB  - The structure of the inclusion complex of diferrocenylenone and beta-cyclodextrin
      prepared by a novel method of solid-grinding was studied by UV, FTIR and powder X
      ray diffractometry. Continuous variation plot proved that 2 : 3 (DFE : beta-CD)
      inclusion complex has been formed. The binding constant of the inclusion compound
      was found to be 1.48 x 10(15) (L4 x mol(-4)) with the data of UV spectroscopy.
      Furthermore, the influence of different solvents and pH on the UV spectrum of DFE
      and beta-CD-DFE was discussed respectively. The results show that different micro
      environment has apparently different effects on the electric spectra of guest and
      inclusion complex.

PMID- 17020042
TI  - [VUV spectral properties of MO-Y2O3-B2O3 : Re (M = Mg, Sr; Re = Eu, Tb)].
AB  - Eu and Tb doped 17MO-7.88Y2O3-75B2O3 samples were prepared by the solid state
      reaction. VUV excitation properties and luminescence properties under VUV
      excitation were studied. Excitation spectra exhibited high absorption in VUV
      region (120-220 nm). There existed strong emission peaking at 591 and 613 nm
      corresponding to the 5D0 --> 7F(J) (J = 1, 2, 3, 4) emission transition of Eu3+
      when MgO-Y2O3-BO3 : Eu was energized by the VUV radiation (147 nm). By the
      introduction of Sr into MgO-Y2O3-BO2O3: Eu absorption peaking at 147 nm and red
      emission peaking at 613 nm are enhanced strongly. Besides the host absorption
      band of MgO-Y2O3-B2O3 : Tb, there existed strong absorption band peaking at 170,
      178, 195, 204, 225 nm corresponding to the 4f(8)-4f(7) 5d transition of Tb3+;
      emission spectra showed strong emission peaks at 491, 547, 590, 621 nm
      corresponding to the 5D4 --> 7F(J) (J = 6, 5, 4 and 3) emission transition of
      Tb3+.

PMID- 17020043
TI  - [Highly sensitive fluorescent reaction of acridine red with chromium (VI) and its
      application].
AB  - A simple and highly sensitive fluorimetric method for the determination of Cr(VI)
      was developed in the present paper. The method is based on the fluorescence
      enhancement of acridine red with Cr(VI) in the sulfuric acid medium. The effects
      of some experimental conditions on the determination of Cr(VI) were investigated
      in detail. The detection limit for Cr(VI) is 0.6 microg x L(-1), and the linear
      range of the determination is 2.0-32 microg x L(-1). The relative standard
      deviation of 11 replicate measurements is less than 2.0%. The proposed method has
      been successfully used to determine Cr(VI) in electroplating solution, waste
      chromic acid mixture, and alloy steel samples. The results obtained were compared
      with the certified values of Cr(VI) in standard samples and those provided by 1,
      5-diphenylcarbazide method with satisfaction.

PMID- 17020044
TI  - [Studies on the mechanism of the interaction between hydrazide-podophyllic
      Ni(II), Co(II), Zn(II) metal complexes and DNA].
AB  - The mechanism of the interaction between hydrazide-podophyllic (HDPP) metal (Me)
      complexes and calf thymus (ct) DNA in Tris buffer (pH 7.08) was studied by
      viscosity measurements, electronic absorption, gel electrophoresis, and ethidium
      bromide (EB) fluorescence spectroscopy. The results from varied experiments show
      that the intensity of the maximal absorption peaks from absorption spectra is
      weakened in the presence of DNA compared with that in the absence of DNA.
      Meanwhile, DNA can remarkably quench the emission intensity of the complex Me
      HDPP system. The Me-HDPP complexes can increase the viscosity of ct DNA slightly
      and catalyze the cleavage of super coiled pBR322 DNA to the nicked form. The
      complexes of Ni-HDPP and Co-HDPP can be bound to ct DNA mainly by interaction,
      while the partial interaction of Zn-HDPP and ct DNA is the major modes. The
      binding constant of Me-HDPP complexes with ct DNA was determined.

PMID- 17020045
TI  - [Decoloring and spectral properties analysis of innoxious ultraviolet
      absorbents].
AB  - The ultraviolet absorbent extracted from mango leaves, was discolored by some
      decoloring agent. Then the spectral properties of the discolored ultraviolet
      absorbents were analyzed. The discolored method of ultraviolet absorbent was
      studied by comparing one with the others. The results showed that the discoloring
      effect was satisfactory by using active carbon, H2O2, citric acid, and oxalic
      acid as decoloring agent. Specially, when oxalic acid was used as decoloring
      agent, the color of the production was slight, the rate of production was high,
      and the absorption effect of ultraviolet ray was well. When the concentration of
      the ultraviolet absorbent solution is 0.5% (w/w), the ultraviolet ray
      transmission was smaller than 0.3% in 200-370 nm, and it increased slightly from
      370 nm. There was a maximum value at 400 nm, approaching 12%.

PMID- 17020046
TI  - [Study on the spectral properties of nickel tetrasulfo-phthalocyanine doped vinyl
      modified silicate glass].
AB  - Nickel tetrasulfo-phthalocyanine (NiTSPc) was successfully doped into
      vinyltriethoxysilane (VTES)modified silicate gel glass by sol-gel technique, IR
      and UV-Vis spectral examination was carried out. The results show that vinyl has
      been introduced into SiO2 network, and the structure of gel glass is therefore
      changed. The encapsulation of NiTSPc does not make any noteworthy changes in the
      composition and structure of gel glass matrix. NiTSPc molecules are well
      dispersed in the organic modified matrix, and the phenomenon of aggregation is
      greatly suppressed.

PMID- 17020047
TI  - [Fluorescence spectral characteristics of human blood and its endogenous
      fluorophores].
AB  - The three-dimensional fluorescence spectra and excitation-emission matrix of
      human blood were measured, and an attempt was made to exploit the endogenous
      fluorophores of major peaks in the UV and visible. The result indicates that the
      absorption peaks of human blood appear at 274, 345, 415, 541 and 576 nm. Based on
      the analysis of fluorescence excitation-emission matrix, the major emission peaks
      of human blood occur at excitation-emission wavelength pairs of 260-630, 280-340,
      340-460 and 450-520 nm, which are attributed to endogenous porphyrins,
      tryptophan, reduced nicotinamide adenine dinucleotide (NADH) or reduced
      nicotinamide adenine dinucleotide phosphate (NADPH), and flavin adenine
      dinucleotide (FAD), respectively. These results can be used to analyze and
      explain the effect of blood on the distortion of fluorescence signal of human
      tissues for optical diagnosis.

PMID- 17020048
TI  - [Spectrometry study on the interaction of Magdala red and bovine serum albumin].
AB  - In the present paper, the interaction of Magdala red and bovine serum
      albumin(BSA) was studied by UV-absorption and fluorescence spectrometry. The
      results of UV-absorption spectrometry show that the way of the interaction of
      Magdala red and BSA should obey the Scatchard Model. In other words, Magdala
      should be combined to some certain regions of BSA. Meanwhile, taking advantage of
      fluorescence quenching, the reaction mechanism of Magdala with BSA was explored.
      Protein molecule conformation change is discussed by synchronous fluorescence
      spectrometry.

PMID- 17020049
TI  - [Application of L-cysteine-capped nano-ZnS as a fluorescence probe to the
      determination of proteins in human serum].
AB  - Nanometer-sized L-cysteine-capped ZnS particles as a fluorescence probe were
      synthesized, and the effect of proteins on the fluorescence intensity has been
      investigated. With deltalambda = 190 nm, the maximum and constant synchronous
      fluorescence enhancement was produced at 268.0 nm and pH 5.12 in the presence of
      proteins. A highly sensitive synchronous fluorescence method for the rapid
      determination of proteins was developed. Under optimum conditions, the
      calibration curve was linear over the range 0.05-6.0 microg x mL(-1) for human
      serum albumin (HSA), and 0.05-8.0 microg x mL(-1) for gamma-globulin (gamma-G),
      respectively. The relative standard deviations of seven measurements were 1.90%
      for 1.0 microg x mL(-1) HSA, and 1.65% for 1.0 microg mL(-1) gamma-G.

PMID- 17020050
TI  - [Spectrophotometric determination of heparin with neutral red].
AB  - The interaction of neutral red and heparin was studied by UV-Vis
      spectrophotometry in pH 3.0 Britton-Robinson (B-R) buffer solution. Neutral red
      has a strong absorbance at 523 nm and the addition of heparin into neutral red
      solution resulted in the decrease in the absorbance value at 523 nm without the
      appearance of new absorbance peak. The decrease in absorbance value was linear
      with the concentration of heparin. The conditions for the interaction were
      optimized and the interferences of coexistent substances were investigated. Under
      the optimal conditions a linear regression equation was obtained as deltaA =
      0.044 + 0.076c (mg x L(-1)) (n = 12, r = 0.997) in the range of 0.10-15.0 mg x L(
      1) with the detection limit of 0.073 mg x L(-1). The molar absorptivity of the
      method was calculated to be 2.037 x 10(6) L x mol(-1) x cm(-1). The method was
      applied to determine the heparin sodium injection solution with satisfactory
      results. The stoichiometry of heparin with neutral red was calculated as 1 : 3.

PMID- 17020051
TI  - [Principal component analysis and cluster analysis of inorganic elements in Panax
      quinque folium. L].
AB  - The contents of elements such as Mg, Al, P, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn,
      As, Se, Sr, Mo, Cd and Pb in twelve Panax quinque folium. L samples were
      determined by means of ICP/MS. The results were used for the development of
      element fingerprint chromatogram. The principal component analysis of SPSS was
      applied for the study of characteristic elements in Panax quinque folium. L. Five
      principal components which accounted for over 90% of the total variance were
      extracted from the original data. The analysis results show that Fe, Al, V, Mn,
      Mg, Sr, Mo, Ca and Cu may be the characteristic elements in Panax quinque folium.
      L. The results of Q-type cluster analysis show that the samples could be
      clustered reasonably into five groups, and the elemental distribution
      characteristics are related to the breeds of Panax quinque folium. L.

PMID- 17020052
TI  - [Determination of rare earth and microelements in Chinese herbal medicine by
      inductively coupled plasma mass spectrometry].
AB  - In this article, through the condition experiment of simultaneous determination
      of rare earth and trace elements in wolfsbane by inductively coupled plasma mass
      spectrometry (ICP-MS), the methods of low temperature ashing and nitric acid
      overoxidation hydrogen (HNO3-H2O2) were compared. It was proved that the sample
      disposed with low temperature ashing for microelements and the sample disposed
      with acid digestion for rare earth satisfied the request for the method of
      determination. The accuracy is between 1.21% and 15.15%, and the precision is
      between 0.38% and 8.54%. The data of the experiment proved that the method
      completely satisfied the request for the determination of rare earth and
      microelements in the sample of Chinese herbal medicine.

PMID- 17020053
TI  - [Study on the method for the determination of soil available B by ICP-MS].
AB  - A method was established for the determination of soil available B by inductively
      coupled plasma mass spectrometry (ICP-MS). Compared to the traditional method for
      B analysis, the recommended method does not need filtration, so it escapes the
      contamination. The method not only proved simple and rapid, but also showed
      satisfying precision and accuracy. The detection limit of this method is 0.009 ng
      x g(-1). The relative standard deviation is 2.66%, and the recovery is 93.0%
      102.0%.

PMID- 17020054
TI  - [Study of determination method of trace elements in white jade snail].
AB  - The contents of six trace elements, Ca, Mg, Fe, Zn, Cu and Co, in white jade
      snail were determined by ICP-AES and AAS using nitrifying method of high pressure
      nitrifying pot. The results of two analysis methods were compared, showing no
      obvious differences. The recoveries were 92.4%-103.0%, and the relative standard
      deviations were less than 2.98%. The experiment proved that white jade snail
      contains rich useful trace elements, and is a kind of green food with high
      nutrition.

PMID- 17020055
TI  - [Study on determination of metal elements in buds of Syzygium aromaticum (L.)
      Merr. et Perry by ICP-AES].
AB  - Determination of metal elements in buds of Syzygium aromaticum (L. )Merr. et
      Perry was studied by ICP-AES after HNO3-H2O2 digestion. The average recovery of
      the method for K, Mg, and trace elements such as Cu, Fe, Cr, Zn, Mn and Pb in the
      buds of Syzygium aromaticum (L.) Merr. et Perry was found to be 91.8% -112.2%,
      while RSD (n = 5) is 0.4% - 4.9% for the metal elements. The method was applied
      to the analysis of some practical samples, and the results obtained were
      satisfactory. There is rich Mn in the samples. It is of important significance to
      assess the value of the Chinese medicine by the determination of trace elements
      in Chinese medicine with ICP-AES.

PMID- 17020056
TI  - [Determination of copper and chromium in the cartridges of permanent marker pen
      and ink by ICP-AES].
AB  - The method for the determination of copper and chromium in the cartridges of
      permanent pen oil base and ink by ICP-AES was reported. This mainly concerned the
      different methods for pretreatment of samples. The study indicated that the
      better method for the pretreatment of the cartridges of permanent pen and the ink
      containing resin is dry ashing at 550 degrees C followed by wet-decomposition
      with mixed acid (V(HNO3) : V(HClO4 = 3 : 1); the better method for the
      pretreatment of water soluble ink is hydrodigestion with mixed acid (V(HNO3 :
      V(HClO4 = 3 : 1). After suitable dilution with acid, copper and chromium were
      determinated by ICP-AES. It was shown that the method is reliable for the test of
      precision and accuracy. RSD and recovery were in the range of 5.9% - 7.9% and 90%
      - 104%, respectively.

PMID- 17020057
TI  - [Determination of Pb and Cd in environmental water sample by on-line mini-column
      preconcentration and flow injection-flame atomic absorption spectrometry].
AB  - Trace Pb and Cd in environmental water samples were preconcentrted and determined
      by on-line mini-column field sampling and flow injection-flame atomic absorption
      spectrometry (FI-FAAS), and the adsorption materials of the column were activated
      carbon loaded 8-HQ, DDTC and APDC. Satisfactory results of the determination of
      Pb and Cd in the certified reference materials (trace elements in water GBW
      08608) and the South lake water were obtained by using the above method. The
      detection limit of 10 mL enrichment of Pb and Cd was 1.58 and 0.062 microg x L(
      1), respectively, and the relative standard deviation of Pb and Cd was 1.62% and
      1.96% respectively.

PMID- 17020058
TI  - [Determination of trace lead in water samples and salt samples by graphite
      furnace atomic absorption spectrometry after cloud point extraction].
AB  - A method was developed for the determination of trace lead in water samples and
      salt samples by GFAAS after cloud point extraction. The parameters of extraction
      system such as pH, the concentrations of the extractant and the surfactant, and
      the time for cloud point extraction were optimized. Under the optimized
      conditions, the detection limits of lead were 0.000 5 microg x g(-1) for salt,
      and 0.01 microg x L(-1) for water, respectively. The proposed method was applied
      to the determination of lead in water samples and salt samples, and satisfactory
      results were obtained.

PMID- 17020059
TI  - [Simultaneous determination of trace arsenic and antimony in textile by
      intermittent flow-hydride generation-atomic fluorescence spectrometry with L
      cysteine as a prereducer].
AB  - A method for the simultaneous determination of trace arsenic and antimony in
      textile by intermittent flow-hydride generation-atomic fluorescence spectrometry
      with L-cysteine as a prereducer was developed. The optimal instrument condition
      was established. The influence factors such as the acidity of sample solution and
      carrier liquid, the concentrations of KBH4 and L-cysteine, the flow rate of
      carrier, and the interference of coexistent elements were investigated. The
      method was convenient and rapid. Under the optimal condition, the detection
      limits were 0.35 and 0.22 microg x L(-1), the relative standard deviations were
      1.3% and 2.8%, and the recoveries were in the ranges of 93.6% - 98.4% and 92.2% -
      103.6% for As and Sb respectively.

PMID- 17020060
TI  - [Measurement of NO2 concentration in atmosphere in Chengdu by solar spectra].
AB  - In the present paper, a new improved method for measuring NO2 concentration of
      atmosphere by using differential optical absorption spectroscopy of solar
      spectrum was reported. The sample solar spectra were collected in Chengdu city
      and Xiling Mountain respectively by a CCD optical multi-channel analyzer. With
      the upper atmosphere solar spectrum as the reference spectrum, by fitting the
      sample spectrum and the reference spectrum using least-square method in five
      spectrum ranges, the various NO2 concentrations (vertical column density) of 3.1
      x 10(16) to 5.8 x 10(16) (molecule x cm(-2)) in Chengdu city and 0.7 x 10(16) to
      1.0 x 10(16) (molecule x cm(-2)) in Xiling Mountain were obtained respectively.
      The NO2 concentrations of atmosphere showed an increasing tendency with the
      rising temperature.

PMID- 17020061
TI  - [Studies on the synthesis of zeolite 4A in mirowave field by means of X-ray
      diffraction].
AB  - Good quality zeolite 4A with homogenous particle size, high whiteness and high
      calcium exchangeability was successfully synthesized in microwave field. The
      effects of the ratio of silica to aluminium, the ratio of water to sodium, the
      power of microwave, and the time of microwave heating on the synthesis of zeolite
      4A were studied by means of X-ray diffraction. And the products were also
      characterized by IR, SEM and DSC. The optimal condition for the synthesis of
      zeolite 4A in microwave was found.

PMID- 17020062
TI  - [Differential kinetic spectrophotometric determination of chlorpromazine
      hydrochloride and promethazine hydrochloride by chemometric method].
AB  - Chlorpromazine hydrochloride and promethazine hydrochloride were oxidized fastly
      resulting in red intermediate product, which was then gradually changed into a
      colorless product by ammonium cerous sulfate in appropriate acidic medium. The
      chemometric multivariate calibration methods, such as partial least squares (PLS)
      and principal components regression (PCR) were applied to the resolution of the
      kinetic curves to determine these two compounds. The linear ranges are 8.3 - 66.7
      mg x L(-1) and 3.3 - 26.7 mg x L(-1) for chlorpromazine and promethazine,
      respectively. The limits of detections are 2.32 and 0.95 mg x L(-1) for these two
      compounds, respectively. This method was successfully applied to the analysis of
      pharmaceutical samples with satisfied results.

PMID- 17020063
TI  - [Stellar spectral recognition based on wavelet de-noising and SVM].
AB  - The present paper describes a new technique for stellar spectral recognition.
      Considering the characteristics of stellar spectral data, support vector machine
      (SVM) was adopted to build a recognition system as kernel. Because stellar
      spectral data sets are usually extremely noisy, the correct classification rate
      of direct applying SVM is low. Consequently, wavelet de-noising method was
      proposed to reduce noise first and extract the main characteristics of stellar
      spectra. Then SVM was used for the recognition. Based on the real-world stellar
      spectra contributed by Jacoby et al. (1984), it has proven that there will be a
      better performance using this composite classifier which combines wavelet and SVM
      than using SVM with principle component analysis data dimension reduction
      technique. From the experiment of comparison of discriminant analysis and SVM
      based on stellar spectra for evolutionary synthesis, we can see that the correct
      classification rate of SVM is higher than that of discriminant analysis methods,
      and a well generalization ability is achieved.

PMID- 17020064
TI  - The nose: gatekeeper and trigger of bronchial disease.
AB  - The nose is strategically placed at the entrance of the airway. Nose breathing
      takes place under physiologic circumstances and protects the lower airways from
      exposure to unconditioned air and exogenous particles. Alternatively, nasal
      disease may have a negative impact on lower airway biology, being involved in
      aggravation of bronchial disease. The interaction between upper and lower airway
      disease has been recognized for centuries. Due to the increase in prevalence of
      allergic diseases during the last decades, new interest has been gained in
      understanding the mechanisms underlying the interaction between rhinitis and
      asthma. Nowadays, allergic rhinitis and asthma are considered part of a global
      airway disease, with both diagnostic and therapeutic consequences for every day
      clinical practice. Besides allergy, other inflammatory conditions of the upper
      airways are associated with lower airway disease via unknown mechanisms. Viral
      rhinitis often coincides with exacerbations of bronchial disease, chronic sinus
      disease with or without nasal polyps frequently relates to bronchial dysfunction
      and occupational rhinitis and asthma are often present in the same individuals.
      In spite of the clinical relevance of considering the airway as one organ with
      major involvement of disease in upper, lower or both parts, many clues to
      understand the pathology still remain to be explored. This manuscript aims at
      providing a comprehensive overview of the current knowledge on the interaction
      between nasal disease and lower airway biology and stresses the importance of
      further research on this important matter.

PMID- 17020065
TI  - The influence of air current on goblet cell density in the mucosa of the normal
      uncinate process in the nasal cavity.
AB  - AIM: To determine the density of goblet cells in the mucosa at the medial site of
      the uncinate process in the nasal cavity where the air current is high and
      compare with the goblet cell density on the protected lateral site of the
      uncinate process, thus establishing the function of the uncinate process in
      protecting the integrity of epithelium, in the meatus medius, from the distress
      caused by continuous airflow. Determining this function could have clinical
      implications, as patients routinely undergo removal of the uncinate process
      during endoscopic sinus surgery. MATERIAL AND METHODS: The material comprised
      pieces of mucosa of 11 uncinate processes from the nasal cavity of 11 autopsies.
      The material was stained with PAS-Alcian blue after which the goblet cells were
      counted using a whole-mount method. Counting was done by only 1 of the authors
      and was not blinded. RESULTS: The density of goblet cells was significantly
      higher on the lateral site than on the medial site of the uncinate process.
      Furthermore, goblet cell density was found to be higher on the superior part of
      the uncinate process, than on the inferior part. CONCLUSION: The results seem to
      indicate that air current has consequential impact on the normal differentiation
      patterns of the epithelium in the nose. The significantly higher goblet cell
      density on the unexposed lateral site of the uncinate process suggests that at
      this site the sinus outlets are protected from air current trauma.

PMID- 17020066
TI  - Effect of endoscopic sinus surgery on antral mucociliary clearance.
AB  - Endoscopic sinus surgery (ESS) is the most used surgical approach in the
      treatment of chronic and recurrent maxillary rhinosinusitis. However, it still
      remains unclear how well surgery restores the mucociliary function in damaged
      maxillary sinus mucosa. There is also controversy whether to enlargen the natural
      ostium or not. We examined the mucociliary clearance (MCC) of maxillary sinuses
      in 27 patients with chronic and recurrent rhinosinusitis. On one side only an
      uncinectomy was done, on the contralateral side a middle meatal antrostomy was
      additionally performed. The mucociliary clearance (MCC) was measured in both
      sides preoperatively and 9 months after the operation. Measurements of the
      mucociliary clearance in maxillary sinuses were done using an isotope method.
      Preoperative mean residual activity on the uncinectomy side was 87.2 % and
      postoperative mean residual activity 94.1 %. On the middle meatal antrostomy side
      mean preoperative residual activity was 92.3 % and postoperative mean residual
      activity 88.4 %. Residual activity was considered as good (< or = 50 %) on the
      uncinectomy side in 2 sinuses (7.4 %) preoperatively and in 1 sinus (3.7 %)
      postoperatively. On the middle meatal antrostomy side residual activity was
      considered good in 1 sinus (3.7 %) preoperatively and in 4 sinuses (14.8 %)
      postoperatively. Mucociliary function remained poor even 9 months
      postoperatively. Surgery did not significantly improve the mucociliary function
      of maxillary sinus mucosa in chronic or recurrent rhinosinusitis. There was no
      statistical difference between operative techniques. In this study it seemed
      however, that uncinectomy combined with the enlargening of the natural ostium may
      restore maxillary sinus mucociliary clearance (MCC) better than uncinectomy
      alone.

PMID- 17020067
TI  - The effects of ventilated and non-ventilated nasal packs on Eustachian tube
      function: nine-step inflation-deflation test results.
AB  - The effects of different types of nasal packs on Eustachian tube function have
      been a source of debate. Past study results have been based on single
      tympanometric evaluations. To our knowledge, this study is the first to use the
      nine-step inflation-deflation test for evaluation of Eustachian tube function in
      patients undergoing nasal packing. No significant difference was observed between
      ventilated or glove-finger nasal packs, in terms of preserving Eustachian tube
      function in our patient population.

PMID- 17020068
TI  - Influence of ethnicity on the frequency of nasal surgery.
AB  - OBJECTIVE: To determine whether surgery for nasal obstruction differs in
      frequency between ethnic groups. METHOD: Ethnicity data was collected from all
      patients attending otolaryngology clinic appointments and compared to census
      data. Odds ratios with confidence intervals were calculated for attendance at
      otolaryngology clinics, rhinology clinics, undergoing septoplasty,
      septorhinoplasty and/ or turbinate surgery for each ethnic group over a 3-year
      period. RESULTS: The ethnic groups of the 39493 outpatient attendees closely
      mirrored demographic data from the 2001 Census. Non-Chinese Asian ethnic groups
      were more likely to undergo septal surgery than the general (mainly white)
      population (odds ratio 1.44, 95% CI 1.25 to 1.66, p < 0.00001), whereas Black
      groups (odds ratio 0.31 [0.23 - 0.41], p < 0.00001) and Chinese (odds ratio 0.28
      [0.11 - 0.70], p = 0.00311) were much less likely. Similar results were found for
      rhinoplasty and turbinate surgery. CONCLUSIONS: There is strong statistical
      evidence for large differences in the frequency of surgery for nasal obstruction
      between ethnic groups. Asian groups were more likely to undergo surgery, whereas
      Chinese and Blacks were less likely than the general population, which was
      predominantly white in this study. This may be due to anatomical variations,
      differences cultural views towards surgery, or inequalities in clinician's
      attitudes.

PMID- 17020069
TI  - Inverted papilloma: feasibility of endonasal surgery and long-term results of 87
      cases.
AB  - BACKGROUND: The aim of this retrospective study was to assess the potentials and
      limitations of endonasal micro-endoscopic sinus surgery in the management of
      sinonasal inverted papilloma (IP) and to demonstrate long-term results. METHODS:
      Eighty-seven patients underwent resection of an IP either via an endonasal, an
      osteoplastic maxillary or frontal sinus or a combined approach. Charts were
      reviewed for presenting symptoms, tumour stage according to the Krouse
      classification, surgical management and follow-up status. RESULTS: Most tumours
      were staged as T2 or T3 (42.5% each). Sixty-eight (78.2%) patients were referred
      for primary surgery. Nineteen (21.8%) patients presented with recurrent disease.
      The majority of IP (70%) were removed via an endonasal micro-endoscopic
      procedure. In 20 (23%) patients a combined approach was performed. The overall
      recurrence rate was 10.3%. Referring to endonasal surgery the incidence of
      recurrent IP was 10% in contrast to 15% after a combined procedure. CONCLUSION:
      Our data show that endonasal micro-endoscopic surgery offers an effective and
      safe treatment modality of IP with insignificant morbidity. Strict application of
      selection criteria, wide removal of the tumour origin along the subperiosteal
      plane as well as drilling the underlying bone and close follow-up of patients are
      mandatory for success.

PMID- 17020070
TI  - Matrix metalloproteinase-2 and -9 expression in sinonasal inverted papilloma.
AB  - STATEMENT OF PROBLEM: Inverted papilloma (IP) is a proliferative lesion of the
      epithelium lining the sinonasal tract, characterized by marked propensity for
      recurrence and association with carcinoma. To determine a putative role of matrix
      metalloproteinase-2 (MMP-2) and MMP-9 in the establishment of IP, their
      expression was studied in IP. METHODS: Archived surgical specimens from 15 IPs
      were studied using immunohistochemistry and compared to 12 nasal polyps (NP), a
      model of chronic respiratory mucosal inflammation, and to 6 control nasal mucosa
      (CM) samples obtained from snorers during turbinectomy. Within IP, MMP-2 and -9
      expression was compared between tumoral areas with hyperplastic epithelium and
      non tumoral areas with nonhyperplastic epithelium. RESULTS: In IP, MMP-2 and MMP
      9 epithelial expression was not different compared to CM and NP. MMP-9 expression
      in submucosal inflammatory cells was not different between IP and CM or NP.
      However, within IP, a significantly increased number of MMP-9 positive
      inflammatory cells in the lamina propria adjacent to the hyperplastic epithelium
      was observed compared to the lamina propria adjacent to nonhyperplastic
      epithelium. CONCLUSION: Our findings suggest that MMP 9 expressing inflammatory
      cells may be involved in the pathophysiology of IP.

PMID- 17020071
TI  - The management of acute visual loss after sinus surgery--two cases of rhinogenic
      optic neuropathy.
AB  - INTRODUCTION: Different causative mechanisms of ophthalmic complications during
      endonasal sinus surgery have been reported. Only a few cases of blindness caused
      by affections of the optic nerve due to inflammatory paranasal sinus disease have
      been described. OBJECTIVE: Inflammatory optic neuropathy shall be considered
      among the causative factors for amaurosis after sinus surgery. MATERIAL: We
      present two patients with dramatic visual decrease occurring two weeks after
      sinus surgery as a result of inflammatory posterior paranasal sinus disease.
      RESULTS AND CONCLUSION: Our therapy including surgical intervention in form of
      orbital or optic nerve decompression accompanied by systemic steroids and
      antibiotic therapy resulted in a significant increase of visual acuity in one
      case and a complete restoration of vision in the other case. In these two cases
      surgical intervention in the described fashion along with systemic steroids and
      antibiotic therapy represented a successful therapeutical approach.

PMID- 17020072
TI  - Mechanical power flow changes during multijoint movement acquisition.
AB  - We investigated the differences in mechanical power flow in early and late
      practice stages during a cyclic movement consisting of upper arm circumduction to
      clarify the change in mechanical energy use with skill acquisition. Seven
      participants practiced the task every other day until their joint angular
      movements conformed to those of an expert. During the practice sessions,
      participants' motions were digitally recorded once a week using four high-speed
      infrared cameras, and the joint kinematics and joint powers of the right arm were
      calculated. With practice, the inflow power derived from the net joint force
      increased at the hand, forearm, and upper arm segments by 143.1 +/- 17.2%, 57.1
      +/- 7.3%, and 198.1 +/- 35.4%, respectively. In contrast, the power caused by the
      muscle joint moments was not significantly increased. These results suggested
      that participants acquired a motor pattern promoting transfer of the joint
      reaction forces. Results may provide some support for Bernstein's (1967) ideas
      that skill acquisition involves improving movement efficiency by greater use of
      nonmuscular forces.

PMID- 17020073
TI  - Effects of movement velocity and maximal concentric and eccentric actions on the
      bilateral deficit.
AB  - Department of Health, Physical Education, Recreation, and Dance at the University
      of Idaho. This study was performed to examine the effects of movement velocity
      and maximal concentric and eccentric actions on the bilateral deficit. Eighteen
      female participants performed maximal unilateral and bilateral knee extensions
      concentrically and eccentrically across six movement velocities (30, 60, 90, 120,
      150, and 180 degrees/s). Repeated measures analyses of variance revealed
      significant differences (p < .025) between bilateral and summed unilateral
      contractions both concentrically and eccentrically at each velocity tested. Post
      hoc analyses revealed that the degree of bilateral deficit increased as movement
      velocity increased for concentric actions (e.g., 17-33% deficit, for 30 and 180
      degrees/s, respectively), and an increasing trend was seen for eccentric actions
      (e.g., 18-25% deficit, for 30 and 180 degrees/s, respectively). These findings
      suggest that with increased velocity, a decreased or incomplete activation of
      fast twitch muscle fibers may have occurred in bilateral actions when compared to
      unilateral actions.

PMID- 17020074
TI  - Reliability of pedometer-determined free-living physical activity data in college
      women.
AB  - This study examined stability and reliability of free-living physical activity
      assessed by pedometer in 69 young female college students (M age = 18.7 years, SD
      = 1.2, range: 18-25 years; body mass index = 23.2 kg/m2, SD = 0.6) for two
      complete weeks (Week 1 and Week 2) separated by 12 weeks. During Week 1,
      participants took an average of 8880 steps/day, SD = 3219, range: 1858-19480;
      during Week 2 9088 steps/day, SD = 3299, range 1736-16837; t (68) = -.568, p =
      .572. In both weeks, only Sunday differed significantly (repeated measures
      analysis of variance; Week 1: p < .0001; Week 2: p < .01) from all other days of
      the week. The computed intraclass correlation between weeks was moderate (.72).
      Group mean pedometer-determined physical activity was stable across 2 weeks
      separated by 12 weeks in this young, healthy sample of women. Individuals within
      these groups held their rank order to a moderate extent over time. These findings
      provide important evidence of the reliability of pedometer-determined physical
      activity data and are of practical importance to study design.

PMID- 17020075
TI  - Pedometer-assessed physical activity in young adolescents.
AB  - The purpose of this study was to evaluate the physical activity (PA) patterns of
      children. Forty-four 7th-grade students (19 boys, 25 girls) recorded pedometer
      data for 2 consecutive weeks. Separate 2 x 3 repeated measures analyses of
      variance were used to examine differences in total steps/day between boys and
      girls and between after-school activity participants and nonparticipants. The
      relative contribution of physical education (PE) and after-school activity (ASA)
      to weekday steps/day was evaluated as a proportion, for example (steps taken in
      PE class/total daily steps taken on a PE class day) * 100. The total sample mean
      was 11,392 steps/day, SD = 4112; for boys, M = 12,490 steps/day, SD=3910, versus
      girls, M = 10,557 steps/day, SD=4142; F=(1, 42) 4.365, p = .043. The sample
      population averaged 2046 steps, SD=945, during PE class; boys=2379 steps,
      SD=1115, versus girls=1782, SD=703; t (42) = 2.15, p = .038, d = .65, which
      represented 18% of the total steps/day on PE days. In comparison, the
      participants accumulated an average of 5366 steps, SD=2590; ASA for boys=5897
      steps/day, SD=2738, versus girls=4963 steps/day, SD=2450; t (42) = 1.190, p =
      .241, d = .36), representing 46% of the steps/day on all weekdays and 47% of the
      total on PE days. Expressed as a rate, the sample population took 45.5 steps/min
      (SD=21) during PE class and 13.1 steps/min (SD = 4.7) in ASA on all weekdays. The
      relative stability of day-to-day behavior in youth is a preliminary finding but
      noteworthy. Although the absolute contribution ofPE class to daily PA was less
      than ASA (i.e., 18 vs. 47%, respectively), the importance of the condensed
      contribution in class was evident when these two activities were expressed as
      rates (i.e., steps/min). These data indicate that youth involved in ASA
      accumulated a greater number of steps on all days, weekend days, and health
      education days when compared to youth not involved in ASA.

PMID- 17020076
TI  - Changing throwing pattern: instruction and control parameter.
AB  - The purpose of this study was to determine the effects of instruction and scaling
      up a control parameter (velocity of throw) on changes in throwing pattern. Sixty
      adult female throwers (ages 20-26 years) were randomly placed into one offour
      practice conditions: (a) scale up on velocity with no instruction, (b) maintain
      constant velocity with no instruction, (c) maintain constant velocity with
      instruction, and (d) scale up on velocity with instruction. Participants in each
      condition were required to practice throwing with the nondominant arm twice per
      week for 5 weeks (10 sessions). Practice consisted of 20 throws per session.
      Participants in conditions including instruction were encouraged to rotate the
      trunk in an attempt to take advantage of the order parameter. Analysis indicated
      that each condition improved relative to use of the open kinetic chain. However,
      participants who increased velocity were more likely to attain maximum use of the
      order parameter with less practice. Additionally, throwers who increased velocity
      without instruction attained an optimal pattern of complete distal lag one
      session earlier than those who increased velocity with instruction. Data
      indicated that for those conditions without instruction, hand to forearm lag (H-F
      lag) occurred before humeral lag. It was concluded that emphasizing proximal
      movement (trunk rotation) without increasing velocity does not result in a final
      pattern that uses H-F lag.

PMID- 17020077
TI  - Perception of kinematic characteristics of tennis strokes for anticipating stroke
      type and direction.
AB  - The purpose of this study was to determine the sources of visual information used
      by highly skilled tennis players in anticipating their opponent's shots. In
      Experiment 1, motion analysis of the strokes showed that the relative motion
      between the racquet and forearm was different between the ground strokes and
      lobs, but there were no reliable kinematic differences when shot direction was
      varied. In Experiment 2, 12 skilled tennis players observed the opponent hitting
      strokes in a normal video or in a point-light display with different segments
      occluded. Players' anticipation accuracy was not degraded by the use of the point
      light display. Occluding the racquet and forearm significantly reduced the
      participant's ability to determine the type of stroke produced.

PMID- 17020078
TI  - Submaximal expression of the bilateral deficit.
AB  - Thirty-six participants performed bilateral and unilateral isometric elbow
      flexion trials at what they perceived to be 100, 75, 50, and 25% of maximal
      effort. Absolute bilateral deficits ranged from--16% at 25% effort to--10% at
      100% effort. The deficit included a component independent of consciousness and a
      component inversely related to intensity attributable to perceptual differences
      between unilateral and bilateral tasks. Forty-two participants performed
      bilateral and unilateral isometric elbow flexion trials at 100, 80, 60, 40, and
      20% of maximal effort. Perception of effort in submaximal bilateral trials was
      consistently and significantly higher (5.5-9.6%) than corresponding unilateral
      trials. These data suggest that the bilateral deficit exists at submaximal levels
      of effort and is based on perceptual and physiological components.

PMID- 17020079
TI  - Training content and potential impact on performance: a comparison of young male
      and female endurance-trained runners.
AB  - The purpose of the present investigation was to compare the content of 8 weeks of
      training in young endurance-trained male and female runners and study the
      potential impact of this training content on performance. Fourteen men and 11
      women performed two criterion exercises until exhaustion on an outdoor track
      before and after the 8-week training period. The first test was a graded exercise
      to determine maximal aerobic velocity (Mav), the velocity at the lactate
      concentration threshold (v-Tlac), and the velocity at delta 50 (v delta50: the
      velocity halfway between Mav and v-Tlac). The second test was a constant run at v
      delta50 to determine the time to exhaustion at this velocity (tlimv delta50).
      Training logs were used to monitor the self-directed training sessions. The
      results showed that the women had a lower training volume but trained at higher
      exercise velocities than the men. However they presented similar values as the
      men for expected temporary performance capacity and did not improve their
      performance (Mav and tlimv delta50) over the 8-week period. After the training
      period, only v-Tlac (absolute and relative values) was slightly but significantly
      increased by training. These results could be due to the fact that both men and
      women did not train more than 10% of the total distance run at exercise
      velocities equal to or higher than their Mav and did not increase their training
      load during the 8-week training period. We suggest that changes in training
      content during the season, such as severe (long-duration or high-intensity)
      training sessions, may have improved their performance capacity.

PMID- 17020080
TI  - Variability in muscle damage after eccentric exercise and the repeated bout
      effect.
AB  - The first purpose of this study was to determine a possible explanation for the
      variability in the response to eccentric exercise by having participants repeat
      the same exercise 1 year apart. The second purpose was to examine whether initial
      injury in response to eccentric exercise was associated with the extent of the
      repeated bout effect (RBE). Male students performed 30 eccentric contractions
      (ECC) of the elbow flexors using a dumbbell set at 80% of the pre-exercise
      maximal isometric force (MIF). Participants were then classified into low (LR;
      n=6), medium (MR; n=6), high (HR; n=5), and higher (HrR; n=7) based on the
      increase in blood creatine kinase (CK) activity. A year later, participants
      repeated this exercise (ECC30). Four days after ECC30, participants performed 70
      eccentric contractions (ECC70). Range of motion, MFI upper arm circumference,
      soreness, and blood CK activity were measured before and up to 9 days after each
      bout. The change in the criterion measures following ECC and ECC30 were similar
      for each group. There were no further changes in all parameters after ECC70 for
      MR, HR, and HrR, although there was a small increase in CK after ECC70 for LR. LR
      showed a smaller RBE after ECC70 compared with the other groups. It is concluded
      that participants who exercised 1 year apart showed remarkably similar responses
      between the bouts. The extent of the RBE following the second bout for the LR
      group is less for participants who demonstrate the least evidence of muscle
      damage after a first exercise bout.

PMID- 17020081
TI  - Perceived effects of emotion intensity on athletic performance: a contingency
      based individualized approach.
AB  - This study, based on the Individual Zones of Optimal Functioning model, examined
      the perceived effect of idiosyncratic emotions and bodily symptoms on athletic
      performance along the entire emotion-intensity range. The participants were 35
      elite Italian athletes, 16 women and 19 men, competing in either figure skating
      or gymnastics. Idiosyncratic emotional descriptors were rated on Borg's CR-10
      scale to estimate the perceived impact on performance and hedonic tone for each
      level of emotion-intensity range. The findings revealed a large interindividual
      variability in the content of emotions as well as in the shape of the curves
      representing the intensity-impact contingencies. At the group level, the emotion
      performance link was positive linear for optimal-pleasant emotions, bell-shaped
      for optimal-unpleasant emotions, and negative linear for both dysfunctional
      unpleasant and dysfunctional-pleasant emotions. The relationship between
      emotional and bodily symptom intensities was positive linear. Implications of the
      findings for estimating total functional effects and individualized interventions
      are suggested.

PMID- 17020082
TI  - Test-retest reliability of a survey to measure transport-related physical
      activity in adults.

PMID- 17020083
TI  - Variability of physical activity patterns by type of day and season in 8-10-year
      old boys.

PMID- 17020084
TI  - Macroscopic aspects of gross motor control: a test of the end-state comfort
      effect.

PMID- 17020085
TI  - Patterns of early involvement in expert and nonexpert masters triathletes.

PMID- 17020086
TI  - [Unsolved problems of human cell defence against radiation].
AB  - The complex of human cell defence systems against gamma-radiation was
      investigated: DNA repair, antiradical system, GST-family M1 and T1, radioadaptive
      response. Were compared in repair-deficient cells the action of natural (carlic
      extract) and synthetic (crown-compound) antimutagens. New approach related to the
      detection of the activity of different defence systems is developing. It helps to
      estimate the individual sensitivity to mutagens.

PMID- 17020087
TI  - [The comparison of molecular-biochemical and cytogenetic analyses of blood cells
      of patients long after the acute radiation sickness].
AB  - Molecular-biochemical and cytogenetic analyses were made on blood cells of 17
      radiation accident victims who, from 1.7 to 43.8 years previously, had suffered
      acute radiation sickness (ARS) ranging from severity grades I to IV. Molecular
      biochemical data were obtained with patients' leukocytes and with mononuclear
      cells on their oxidative status by a) the level of an anion-radical O2*- in the 3
      (4,5-dimethyl-2-thiazol-2-yl)-2,5-diphenyl-2-tetrazolium bromide (MTT) test and
      b) the sum of reactive oxygen species in the 2,7-dichlorodihydrofluorescein
      diacetate (DCFDA) test together with a test for DNA strand unwinding in alkaline
      conditions by measurements of fluorescence intensity of ethidium bromide. Each
      parameter was measured in freshly sampled cells and during a 5-hour incubation as
      absolute means on 5 measurements and in % change from the initial values.
      Cytogenetic data were obtained from the standard metaphase preparations scored
      for routine unstable chromosomal aberrations (us-CA)--dicentrics; and stable
      aberrations (sCA)--translocations. The latter ones were assayed by the FISH
      method using whole chromosome 2, 4 and 12 fluorescent probes and scaled up to
      genome equivalence. For all patients reduced oxidative status of about 25-30% was
      obtained by the MTT-test (p < 0.005), and the DCFDA-test (p < 0.027). The yield
      of usCA depended on the time after irradiation with higher yields associated with
      the shorter postirradiation times and reducing almost to expected background
      frequencies. The yield of sCA was high for all patients, correlating with the
      severity of ARS whilst the molecular-biochemical parameters showed no
      relationship with ARS. A correlation was observed between parameters of oxidative
      status and % of cells with usCA: by the MTT-test r = from 0.50 up to 0.61 (p =
      from 0.06 up to 0.003), but by the DCFDA-test the strength of correlation was
      smaller: r = from 0.38 up to 0.48. An inverse correlation was found between
      initial oxidative state of mononuclear cells and the frequency of CA in
      lymphocytes. Similarly a marked inverse correlation between degree of DNA
      unwinding by the ethidium bromide assay on leukocytes and sCA in lymphocytes was
      also noted. The feasibility of radiation-induced delayed genomic instability in
      vivo for humans long time after irradiation is discussed.

PMID- 17020088
TI  - [The potential of 1,1'-hexamethylenebis [3-(3,5-dichloro-4-pyridyl)] urea to
      modify genotoxic actions of chemical mutagens in various test-systems].
AB  - The main tasks of this investigation were to investigate the potential genotoxic
      effect of 1,1'-hexamethylenebis [3-(3,5-dichloro-4-pyridyl)] urea and to analyze
      its capacity to induce adaptive response (AR) against chemical mutagens in
      various test-systems. Microbiological, cytogenetical and biochemical end-points
      were used. The sensitivity of test systems can be arranged as followed: human
      lymphocyte cultures > Chlamydomonas reinhardtii > Hordeum vulgare. It was
      obtained that HMPU can induce oxidative stress in Chlamydomonas reinhardtii cells
      (7.5 x 10(-4) mol/l) and at appropriate experimental conditions can trigger an AR
      against chemical mutagens in Hordeum vulgare (7.5 x 10(-3) mol/l) and human
      lymphocytes (10(-5), 10(-6) mol/l). The extent of the AR induction was closely
      connected with the increase of the inter-treatment time between the conditioning
      concentration of HMPU and the challenge concentration of chemical mutagens.

PMID- 17020089
TI  - [The protective effect of newly synthesized compounds against the action of UV-C
      irradiation on human lymphocytes in vitro].
AB  - In this work we present our data about the protective effect of the newly
      synthesized compound 1-(4-fluorphenyltioureido)-4-methyl-piperazyne (FTMP)
      against high doses UV-C irradiation using human lymphocytes in vitro as a model
      system. The endpoint used was chromosome aberrations. The genotoxic effect of
      different UV-C doses in the range from 10 J/m2 to 200 J/m2 was evaluated.
      Studying the protective effect of FTMP, it was obtained that a low, adaptive
      concentration (10(-6) mol/l) applied before harmful doses of UV-C irradiation
      (100 J/M2 and 150 J/M2) induces the yield of chromosome aberrations lower than
      theoretical, estimated as a sum of single effects of both agents. A tendency for
      reducing the damage effect of UV-C irradiation was established. The effect is the
      most clear when a 4-hour interval between the treatments was used. The mitotic
      index was not affected. These results pointed out the ability of FTMP to decrease
      the damaging effect of UV-C irradiation in this type of cells and possess the
      potential to induce the adaptive response against the damaging effect of UV-C
      irradiation.

PMID- 17020090
TI  - [A model for indication of DNA functional and structural changes at low-dose
      radiation].
AB  - The work offers an "in vivo-in vitro" model which allows to identify DNA's both
      structural and functional damages caused by gamma-irradiation in doses from 0.02
      to 0.25 Gy. As a donor the authors used an irradiated pTTQ 19 plasmide which had
      two marker genes: the ampicilline-resistant gene (amp(r)) and beta-galactosidase
      structural gene (lacZ alpha). E. coli GM 109 bacterial stamm transformed by the
      irradiated plasmide was used as a recipient. The structural damages of the
      irradiated plasmide were registered by DNA electrophoretic analysis in agarose
      gel. The plasmide DNA dysfunctions were assessed by its ability to pass on
      ampicilline resistance to E. coli bacterial cells as well as by beta
      galactosidase level. The irradiated plasmide was found to have a tendency to
      decrease beta-galactosidase activity and number of E. coli ampicilline-resistant
      transformants depending on the received radiation dose: by 24.5% (0.05 Gy), 30.9%
      (0.19 Gy), and by 40.2% (0.25 Gy).

PMID- 17020091
TI  - [Genetic polymorphism of glutathione-S-transferases and inhibition of DNA
      repair].
AB  - A complex investigation of different cell defence systems, such as: DNA repair,
      antioxidant system (SOD), xenobiotic detoxification system (glutathione-S
      transferases M1 and T1), radioadaptive response (RAR) in lymphocytes of patients
      with hereditary disease of connective tissue (Elers-Danlose syndrome) was carried
      out. The frequency of genotype GSTM1 (0/0) in children with Elers-Danlose
      syndrome (23%) is lower as compared to the control group (44%). The lymphocytes
      of children with Elers-Danlose syndrome were characterized by reduced ability to
      repair gamma-induced damage of DNA. At given size of the samples of examined
      children no correlative relationships between GST-status of organism and the
      condition of other cell defence systems were revealed. The data obtained
      demonstrate the individual peculiarities of the defence systems in repair
      deficient cells of the examined children.

PMID- 17020092
TI  - [The influence of gamma-irradiation in low doses on the rate of dominant lethal
      mutations in drosophila melanogaster].
AB  - The dose-rate effect of acute and chronic irradiation in the dose of 0.2 Gy in
      Drosophila melanogaster repair (mei-41, mus209 [Russian character: see text]
      mus309) and free radicals detoxication (sod) mutant strains was investigated. Was
      shown the lack of dose rate effect on the rate of dominant lethal mutations in
      mei-41, mus209 and sod. However in mus309, that has defect in the main Drosophila
      pathway of the DNA double strand breack repair, the increase of the mutation rate
      after chronic irradiation was observed (inverse dose-rate effect). The obtained
      results suggest the main role of DNA double strand breack repair in dose-rate
      effect formation in Drosophila.

PMID- 17020093
TI  - [Genome instability in the F1-progeny of mice irradiated by ionizing radiation as
      determined by micronucleus assay].
AB  - The F1-progeny of BALB/c male mice chronically exposed to low-dose gamma
      radiation (0.1; 0.25 and 0.5 Gy; dose rate 0.01 Gy/day) as well as the F1-progeny
      of females exposed to acute X-radiation (0.5; 1.0 and 2.0 Gy; dose rate 0.1
      Gy/min) shown the significant elevated micronuclei frequencies in bone marrow
      erythrocytes, as compared to the F1-progeny of unirradiated males and females.
      The increase in the micronuclei frequency in the F1-progeny was determined by the
      dose of irradiation of parents. The values of elevated micronuclei frequency in
      the F1-progeny of chronically irradiated males and acutely irradiated females for
      a dose of 0.5 Gy were comparable. The micronuclei frequencies in the F1-progeny
      of irradiated females and males for this dose were in 1.5 and in 1.6 times higher
      than ones in the F1-progeny of unirradiated mice correspondingly. The results
      suggest the possibility of transfer of genome instability from irradiated parents
      to the somatic cells of the F1-progeny via non-lethally damaged germ cells of
      parents.

PMID- 17020094
TI  - [Life-span in generations of chronic irradiated Drosophila wild type isogenic and
      geterogenic strains].
AB  - With the goal to study radioadaptation on life-span and observe the role in this
      phenomenon of genotype, we investigated the dynamics of life-span in 14
      consistent generations after chronic gamma-irradiation in heterogenic (Canton-S)
      and isogenic (Oregon-R spa) Drosophila wild type strains. The gamma-source was
      226Ra in dose 60 cGy per generation. The animals kept in standard conditions (25
      degrees C and 12 h lighting). Was shown, that the dynamics of median life-span in
      wild type strains Canton-S and Oregon-R spa was different and the character of
      alterations depends on genetic heterogeneity. After chronic irradiation in
      generations in heterogenic line Canton-S since 5 generation cyclic life-span
      oscillations disappeared, values of median life-span leave on a plateau. Since
      the 8th generation the life-span values of irradiated populations exceeded all
      the control values. As a result of the irradiation practically in all generations
      in isogenic line Oregon-R spa occurs increasing of life-span with the comparing
      to non-irradiated control. This is possible due to the positive influence of
      radio-induced heterogeneity on the life-span of isogenic strain. Thus, chronic
      irradiation led to violation of natural cyclic dynamics of Drosophila life-span
      in heterogenic strain, discovered in the end 80-s' years by F. Lints and D.
      Ismaylov. Irradiation of isogenic strain led to increasing of life-span in all
      generations.

PMID- 17020095
TI  - [Transgenerational transmission of radiation induced genomic instability].
AB  - Stability of genome is one of the evolutionary important trait of cells. Various
      mutations (gene, chromosomal, genomic) as well as artificial manipulations with
      genomes (inbreeding, DNA transfection, introduction of Br-DU in DNA) cause the
      genetic instability. Ionizing radiation is known as the factor which induced
      instability of genome in late mitotic descendants of cells after in vitro and in
      vivo exposure. Radiation induced genetic instability can be transmitted through
      germline cells. On the cell level both types of radiation induced genomic
      instability are manifested in elevated frequency of mutations, chromosome
      aberrations, micronuclei, increased radiosensitivity, disappearance of adaptive
      response, changes in gene expression. In studies of 1970-1980 years clear
      evidences on the different morphological and functional injuries in tissues of
      irradiated organisms as well as in tissues of the progeny of exposed parents were
      obtained. On the organism level the instability of mitotic and of meiotic progeny
      of irradiated cells is resulted in increased risk of cancer and of other somatic
      diseases. It seems to be useful to review the earlier radiobiology literature
      where delayed and transgenerational effects of ionizing radiation on tissues and
      on organisms level were clearly shown in animals. For the estimation of
      pathogenic role of radiation induced genomic instability in humans, particularly
      in children of exposed parents the parallel study of the same human cohorts using
      clinical parameters and various characteristic of genomic instability seems to be
      very important.

PMID- 17020096
TI  - [The theory and practice of constructing calibration curves in biodozimetry].
AB  - The methodical peculiarities of experimental construction of regression "dose
      effect" relationships used for the dose reconstruction are discussed. The method
      of computer simulations is applied to study the efficiency of different
      statistical procedures for plotting regression curves as well as the dependence
      of errors in dose prediction on the volume of examined material and on the choice
      of doses for a calibration curve. The causes of essential variability of
      calibrations obtained by different teams of researchers are discussed. A number
      of methodical recommendations is given for statistical processing of cytogenetic
      data. The procedure of constructing calibration dose dependence of the frequency
      of dicentrics on the basis experiments with in vitro gamma-irradiation of
      lymphocytes from blood samples of 5 donors is considered in detail. The
      expressions for statistical errors occurring in the dose reconstruction made on
      the base of the frequency of aberrations were derived and checked by the computer
      experiment.

PMID- 17020097
TI  - [Cytogenetic effects of low dose radiation with different LET in human peripheral
      blood lymphocytes and possible mechanisms of their realization].
AB  - The induction of chromosome damage by the exposure to low doses of gamma-(60)Co
      and accelerated carbon ions 12C in peripheral blood lymphocytes of different
      donors was investigated. The complex nonlinear dose-effect dependence at the
      range from 1 to 50-70 cGy was observed. At the doses of 1-5 cGy the cells show
      the highest radiosensitivity (hypersensitivity), mainly due to the chromatid-type
      aberration, which is typical to those spontaneously generated in the cell and
      believed not to be induced by the irradiation of unstimulated lymphocytes
      according to the classical theory of aberration formation. With the increasing
      dose the frequency of the aberrations decreases significantly, in some cases up
      to the control level. At the doses over 50-70 cGy the dose-effect curve becomes
      linear. The possible role of the oxidative stress, caused by radiation-induced
      increase in mitochondrial reactive oxigen species (ROS) release in the phenomenon
      of hypersensitivity (HS) at low doses is discussed as well as cytoprotective
      mechanisms causing the increased radioresistance at higher doses.

PMID- 17020098
TI  - [The cytogenetic effects of low doses of accelerated charged particles in human
      blood lymphocytes in vitro].
AB  - The aim of the investigation was the study of cytogenetic effects in human blood
      lymphocytes of low doses of ionizing radiation in vitro. The analysis of unstable
      chromosome aberrations in human lymphocytes after irradiation by the accelerated
      ions 12C with the energy 500 MeV/nucleon and LET 10.7 keV/microm was carried out.
      Blood samples were irradiated on Nuclotron of the High Energy Laboratory of the
      Joint Institute for Nuclear Research. The doses of irradiation were in the range
      from 0.05 up to 1.0 Gy. Was shown that the frequency of unstable chromosome
      aberrations depends from the dose of ionizing radiation and can be described by
      linear function. At the doses 0.25-0.50 Gy the dose-independent curve was
      obtained for dicentrics and centric rings. The frequencies of dicentrics and
      centric rings as markers of the radiation action were slightly different for
      different donors that could be explained by different radiosensitivity. Using the
      calibration curve obtained earlier for gamma-rays coefficients of relative
      biological efficiency of accelerated 12C with the energy 500 MeV/nucleon were
      defined: they varied from 1.0 at the doses (0.5-1.0 Gy) up to 3.2 at the lower
      doses (0.05-0.25 Gy).

PMID- 17020099
TI  - [The problem of the transgeneration phenomenon of genome instability in sick
      children of different age groups after the accident at the Chernobyl Nuclear
      Power Plant].
AB  - A complex genetic examination of children which belong to two cohorts and their
      parents were carried out. The first cohort included children and constantly
      living on territories contaminated with radionuclides (Novozybkov district,
      Bryansk region). They were subdivided in groups according to the ontogenetic age
      periods of development of their parents at the time of the Chernobyl accident. In
      the children born in 1986-1995 the level of aberrant genomes is significantly
      higher as compared to the control (p < 0.001). In children born in 1998-2002 the
      differences are insignificant (p > 0.05). The frequency of aberrant genomes had a
      tendency to decrease with the period of time between the birth date of a child
      and the moment of the accident. Analysis of the results of cytogenetic
      investigation for the same living on territories with different densities of
      radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402
      kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average
      frequencies of chromosome aberrations. The second cohort included children born
      in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers)
      and unirradiated mothers living on territories without radionuclide
      contamination. These children also displayed increased frequencies of aberrant
      genomes as compared to the control (p < 0.001). The analysis of the dynamics
      years of birth of cytogenetic disturbances in the same cohorts of children showed
      the average frequencies of aberrant genomes remain higher than the control level.
      In most of the children of both cohorts the repair synthesis of genome DNA by
      gamma- and UV-radiation is reduced as compared to one in the children from the
      control group.

PMID- 17020101
TI  - [Induction of chromosome aberrations and micronuclei in human peripheral blood
      lymphocytes at low dose of radiation].
AB  - The chromosome damage induced by the doses of y-irradiation 6)Co in peripheral
      blood lymphocytes was studied using different cytogenetic assays. Isolated
      lymphocytes were exposed to 0.01-1.0 Gy, stimulated by PHA, and analysed for
      chromosome aberrations at 48 h postirradiation by metaphase method, at 49 h--by
      the anaphase method, at 58 h by micronucleus assay with cytochalasin B and,
      additionally, micronuclei were counted at 48 h on the slides prepared for the
      metaphase analysis without cytochalasin B. Despite of the quantitative
      differences in the amount of chromosome damage revealed by different methods all
      of them demonstrated complex nonlinear dose dependence of the frequency of
      aberrant cells and aberrations. At the dose range from 0.01 Gy to 0.05-0.07 Gy
      the cells had the highest radiosensitivity mainly due to chromatid-type
      aberration induction. With dose increasing the frequency of the aberrant cells
      and aberrations decreased significantly (in some cases to the control level). At
      the doses up to 0.5-0.7 Gy the dose-effect curves have become linear with the
      decreased slope compare to initial one (by factor of 5 to 10 for different
      criteria) reflecting the higher radioresistance of cells. These data confirm the
      idea that the direct linear extrapolation of high dose effect to low dose range-
      the procedure routinelly used to estimate genetic risk of low dose irradiation-
      cannot be effective and may lead to underestimation of chromosome damage produced
      by low radiation doses. Preferences and disadvantages of used cytogenetic assays
      and possible mechanisms of low ionising radiation doses action were discussed.

PMID- 17020100
TI  - [The influence of the water with decreased content of heavy stable hydrogen and
      oxygen (18O) isotope on development of radiation injuries at gamma-radiation in
      low dose].
AB  - The investigations of the water with decreased content of heavy stable hydrogen
      and of oxygen (18O) isotope received by the method of rectification were
      conducted on development of radiation injuries in organisms of the experimental
      animals. The objects of the investigation were male mice of Balb/c line. The
      animals were irradiated at the unit PX-gamma-30 with the gamma-radiation source
      60Co in the dose of 25 sGy. It was observed that the water with decreased content
      of heavy stable hydrogen and of oxygen (18O) isotope influences positively the
      processes of restoration. It was manifested in decrease of the degree of gravity
      of radiation injuries in immune system organs (thymus and spleen), peripheral
      blood and marrow cells.

PMID- 17020102
TI  - [Chronic low doze ionizing irradiation and polyfactors of adaptation].
AB  - The analysis of cytogenetic anomaly dynamics in conditions of chronic low doze
      effect of ionizing irradiation in generations of genetically homogeneous
      laboratory line of mice CC57W/Mv and genetically heterogeneous populations of
      vole's species, trapped in alienation zone of Chernobyl's NPP in places with
      different levels of radio nuclide contamination in 1994-2001 was carried out. The
      data about the physiological adaptation to ionizing irradiation effects under age
      of linear mice and non-linearity of frequency changes of separate cytogenetic
      anomalies in generations as laboratory line of mice, and genetically
      heterogeneous populations of vole's species were obtained. Was supposed, that the
      number of non-linear effects of the ionizing irradiation in low doze range could
      be stipulated by comparability between the intensity of it's damage effects and
      the activation by it the polyfactor systems of anti oxidant ones, reparation
      events, and also elimination of defective cells.

PMID- 17020103
TI  - [Consequences for posterity of two generations of an irradiation pregnant from
      females rats Wistar in small doses during a bookmark of reproduction system of
      fetuses development of posterity of the second generation and it reproduction
      function].
AB  - With the purpose of study of consequences for development and reproduction
      functions of posterity of the second generation from females rats Wistar of a
      total unitary gamma-irradiation in dozes 0.25; 0.5 and 1 Gy (capacity of a doze
      0.03 sGy/s) on 10th day of pregnancy (the period of the onset of fetuses
      reproduction system development) is investigated more than 630 females, 1400 with
      the age of 19th days, and about 3200 young rats. The revealed
      deviations(rejections) in development of posterity of two generations parents,
      antenatal irradiated in not sterilizing dozes, in he period of a beginning of
      formation of reproduction system, them a variety at different dozes of radiating
      influence, shown as at posterity of the irradiated mothers, and fathers, testify
      about instability genoms in a line of generations requiring the account and
      acceptance of necessary measures for preservation normal genofund.

PMID- 17020104
TI  - [The quantitative criteria of the transition from norm to pathology at chronic
      exposure of physical factors].
AB  - In this work the quantitative approaches for the characteristic of the change in
      the condition of separate systems and stability of an organism are considered at
      chronic exposure of electromagnetic fields of a radio-frequency range. The
      quantitative criteria for the substantiation of transition from norm to pathology
      and definition of the thresholds of harmful action of physical factors are
      developed. The results of the experimental research of the immune system
      condition at EMF RF exposure were considered. It can be a basis for the
      definition of maximum permissible levels of these factors for professional
      workers and for the population.

PMID- 17020105
TI  - Medicare final rule calls for increased reporting of quality data.

PMID- 17020107
TI  - Patient safety alert. Hospital reports critical results within one hour.

PMID- 17020106
TI  - Address growing problem with credentialing.

PMID- 17020108
TI  - Discharge planning advisor. 'Basics' may be pushed aside in rush to trendier
      remedies.

PMID- 17020109
TI  - Insurers using publicly reported quality data.

PMID- 17020110
TI  - Don't declare QI victory too soon.

PMID- 17020111
TI  - No A+ for United States on new national health care scorecard.

PMID- 17020112
TI  - Congress considers plan that would keep payment cuts for some doctors.

PMID- 17020113
TI  - Continuity of care threatened by court ruling, industry reps claim.

PMID- 17020114
TI  - PE-RVU changes could cut major procedures by 10 percent.

PMID- 17020115
TI  - [The mechanism for the development of digestive system movement and the autonomic
      nervous control].

PMID- 17020116
TI  - [The ideal forms of specialists and the specialist system in relation to
      society].

PMID- 17020117
TI  - [Specialist system designed for patients].

PMID- 17020118
TI  - [The role of the Japan Surgical Society in the training of surgical specialists].

PMID- 17020120
TI  - [Technical evaluation of surgeons in the specialist system].

PMID- 17020119
TI  - [The specialist system promoted by the Japanese Society of Digestive System
      Surgery--for the training of subspecialists].

PMID- 17020121
TI  - [Evaluation of medical technology and problems in mixed patient care].

PMID- 17020122
TI  - [Evaluation of surgical technology and keypoints in setting the standard for each
      health facility].

PMID- 17020123
TI  - [The insurance system for cardiovascular surgery: a comparison with overseas].

PMID- 17020124
TI  - [Japanese surgeons must act on unreasonable evaluation--a comparison with
      overseas].

PMID- 17020125
TI  - [Evaluation of medical technology in relation to medical fees in pediatrics and
      the problems associated with the system--examination of the 2006 revision of
      medical remuneration].

PMID- 17020126
TI  - [A model project to survey and analyze the reports on abnormal deaths and deaths
      related to medical actions].

PMID- 17020128
TI  - [Legal aspects of a model project on medical practice].

PMID- 17020127
TI  - [Investigation on deaths in abnormal circumstances and the systems of physician
      control in the English bloc].

PMID- 17020129
TI  - [The current status and future of the model project on medical practice--from the
      administrative aspect].

PMID- 17020130
TI  - [Participation of endogenous brain histamine on learning and memory].
AB  - It is well known that histamines play an important role as a neurotransmitter in
      the central nervous system and participate in several physiological functions,
      such as the regulation of body temperature, food intake, circadian rhythm and
      analgesia. Since the first report by de Almeida and Izquierdo that histamines
      facilitate memory performance in mice, it has been revealed that the
      histaminergic nervous system in the brain plays a crucial role in learning and
      memory functions. First, we demonstrate the effects of histamines and
      histaminergic drugs on learning and memory using active avoidance and 8-arm
      radial maze tests. Many reports suggest that acetylcholine and N-methyl-D
      aspartate (NMDA) receptors play an important role in learning and memory. In this
      report, we also describe the interaction between histamine-induced memory
      facilitation and acetylcholine or NMDA receptors.

PMID- 17020131
TI  - [The n-3 fatty acid/dopamine hypothesis in schizophrenia].
AB  - The dopamine hypothesis of schizophrenia has been most influential since the
      1970s. Normally, the prefrontal dopamine system suppressively controls the limbic
      dopamine system. Since the activities of prefrontal dopaminergic neurons are
      reduced in schizophrenia, the suppressive effect of the prefrontal area on the
      limbic system is reduced, and activities of the limbic dopamine system are
      enhanced. Reduced activities of the prefrontal dopamine system cause negative
      symptoms and cognitive disorders, and the increased activity of the limbic
      dopamine system induces positive symptoms. While the dopamine hypothesis explains
      the relationship between intracranial dopamine kinetics and psychiatric symptoms
      in schizophrenia, it is not a direct explanation of its etiology. The cause of
      the activities of dopaminergic neurons in schizophrenia and the resultant
      symptoms are unknown. n-3 Fatty acids are not synthesized in the human body and
      are called "essential fatty acids". Since the late 1980s, it has been revealed
      that the n-3 fatty acid concentration is reduced in the plasma and erythrocyte
      membranes of schizophrenic patients, and that the administration of n-3 fatty
      acids is effective for the treatment of schizophrenia. However, how n-3 fatty
      acid deficiency induces psychiatric symptoms remains unclear, and the mechanism
      of the therapeutic effect of n-3 fatty acids has not been clarified. Recently,
      the dopamine hypothesis and n-3 fatty acid hypothesis have been suggested to
      represent different aspects of the same pathology of schizophrenia. In
      schizophrenia, the inactivation of phospholipase A2 causes an excessive depletion
      of essential fatty acids from the Sn2 position of cell membrane phospholipids,
      and the brain concentrations of essential fatty acids decrease. This causes
      decreases in dopamine vesicles, dopamine concentration, and D2-receptors at
      prefrontal presynaptic terminals. The reduced activity of dopaminergic neurons in
      the prefrontal area induce negative symptoms and cognitive disorders.
      Furthermore, as the suppression of activities in the limbic dopamine system by
      the prefrontal area is reduced, the dopamine concentration and D2-receptors
      increase in the striate body. As a result, the hyperactivity of the limbic
      dopamine system induces positive symptoms. The administration of antipsychotics
      and n-3 fatty acids act on different points in this etiological cascade.

PMID- 17020132
TI  - [Present status and prospects about an animal model of post-traumatic stress
      disorder in rats using a shuttle box].
AB  - Wistar rats exposed to inescapable foot shocks (IS) for 2 wk exhibited PTSD-like
      bi-directional changes similar to avoidance/numbing and hyperarousal symptoms
      when placed in a shuttle box. Paroxetine administration after IS reduced the
      hyperarousal-like behavior, and its therapeutic effect on avoidance/numbing-like
      behavior was also significant. Further, F344 rats, which were more vulnerable to
      various kinds of stressors, showed more significant 'bi-directional changes' than
      Wistar rats. Thus, the paradigm we have developed could serve as a useful PTSD
      model because of its face, predictive, and construct validity. Moreover, the
      intensity of IS dose-dependently induced PTSD-like behaviors and hypo-activity in
      a shuttle box, similar to the 'avoidance/numbing' that reappeared in a square
      open field. These findings further support the construct validity of this
      paradigm. Both electro-convulsive shock treatment before and after IS ameliorated
      the PTSD-like behaviors in this model, so electro-convulsive therapy may be an
      effective method for prevention and medical treatment of PTSD in the future. On
      the other hand, pretreatment with fluvoxamine before IS did not have a
      significant effect, and its improving effect after IS was only observed for
      'hyperarousal' behavior. Lastly, we recently developed a useful criterion, which
      is represented as a 'bi-directional index', for separating real PTSD rats from
      those exposed to IS.

PMID- 17020133
TI  - [Influence of stress on the activation of CaMKII in the brain].
AB  - Stress can affect signal transduction in the brain, possibly resulting in the
      development of certain psychiatric disorders, such as depression and
      posttraumatic stress disorder. Calcium/calmodulin-dependent protein kinase (CaMK)
      II is one of the protein kinases abundantly expressed in the brain, especially in
      the hippocampus, which plays an important role in synaptic plasticity, and is
      therefore involved in memory formation. Here, we provide a brief overview of the
      effects of stress on the levels of CaMKII and phosphorylation (activation) of
      CaMKII in the rat hippocampus through the glutamatergic system, alpha-amino-3
      hydro-5-methyl-4-isoxazolepropionate (AMPA) receptors. Furthermore, we highlight
      the possible links between stress-mediated CaMKII modulation and the
      pathophysiology of psychiatric disorders.

PMID- 17020134
TI  - Improved diagnostic and real-time pcr in rapid screening for Salmonella in the
      poultry food chain.
AB  - The goal of this study was to improve the diagnostic applicability of genus- and
      serovar- (S. Enteritidis and S. Typhimurium) specific PCR systems in screening
      faecal and caecal samples of poultry, poultry feed and poultrymeat for
      Salmonella, by keeping the opportunity to obtain Salmonella cultures from
      positive samples. Peptone broth pre-enrichment cultures of the samples were
      tested by PCR. In faecal and caecal samples from broiler chicks a strong
      inhibitory action was frequently observed. This could be reduced markedly by the
      addition of bovine serum albumin (BSA) acting as amplification facilitator. The
      results of testing pre-enrichment cultures from artificially contaminated faecal,
      poultry feed and poultrymeat samples (using S. Enteritidis, S. Typhimurium and S.
      Hadar as contaminants) suggest that the sensitivity of the above systems is 10(1)
      10(2) CFU g(-1) sample. The testing of 95 caecal samples from slaughtered chicks
      resulted in 49% culture-positive and 76% PCR-positive samples. The suitability of
      a generic real-time PCR for testing faecal samples of poultry was also studied.
      Its detection limit for these samples was found to be lower than that of the
      diagnostic PCR system. Both methods reduced the time required for Salmonella
      detection to 24-30 h, and the advantage of the real-time PCR was its increased
      sensitivity. We have established a diagnostic and a real-time PCR system for
      rapid and reliable genus- and serovar- (S. Enteritidis and S. Typhimurium)
      specific detection of Salmonella for monitoring purposes in the poultry food
      chain. Sensitivity is equal to, or higher than, that of the standard bacterial
      culture method, and the method still provides the Salmonella culture if needed.

PMID- 17020135
TI  - Aetiology of caprine footrot in Extremadura region, Spain.
AB  - The present study reports on the location of major foci of footrot in goats in
      the Extremadura region of Spain by the determination of locally occurring
      strictly anaerobic microorganisms involved in the pathogenesis and development of
      this disease. The most commonly isolated microorganisms belonged to the genera
      Dichelobacter, Fusobacterium, Porphyromonas and Prevotella; these were found in
      conjunction with other species of minor importance. The species most frequently
      isolated were Fusobacterium necrophorum (40%), Dichelobacter nodosus (31.7%),
      Porphyromonas asaccharolytica (21.1%) and Prevotella melaninogenica (12.9%).
      Virulence factors identified in the isolated microorganisms included haemolysins,
      elastases and lecithinases, which enabled the organisms involved to initiate
      and/or aggravate the disease. Serotyping was performed for Dichelobacter nodosus
      isolates, since this species is responsible for triggering the process of
      infection. A and C were the most frequently isolated serovarieties (representing
      40.7% and 25.9% of the cases, respectively).

PMID- 17020136
TI  - Effects of environmental temperature on thyroid hormones in the barn owl (Tyto
      alba).
AB  - The basic patterns of thyroid hormones [thyroxine (T4) and 3,3',5
      triiodothyronine (T3)] and the T4 and T3 responses induced by thyrotropin
      releasing hormone (TRH) are reported in captive female barn owls (Tyto alba)
      during the non-breeding period. The main findings of the study, conducted on a
      total of 10 owls, are as follow: (1) The thyroid gland of barn owl can be
      stimulated by the classical TRH stimulation test. (2) T3 response was much more
      pronounced both under cold (around 10 degrees C) and warm (around 20 degrees C)
      conditions, whereas T4 response ranged so widely that we could not point out any
      significant change in it. (3) Basal T3 plasma level was significantly (p = 0.036)
      higher in birds exposed to cold temperature, and they responded to TRH treatment
      with a lower plasma T3 elevation than the birds kept in a warm chamber. This
      pattern, however, cannot be explained by increased food intake, but is in
      agreement with the fact that enhanced T3 level may account for higher avUCP mRNA
      expression, which results in higher heat production on the cell level. From the
      results it is concluded that altering T3 plasma level plays a significant role in
      cold-induced thermoregulation.

PMID- 17020137
TI  - Rumen fermentation response to a direct-fed xylanase enzyme preparation from
      Thermomyces lanuginosus in sheep.
AB  - A study was conducted to obtain data on the effects of a fungal fibrolytic enzyme
      preparation (Rumino-zyme, with 250 FXU/g xylanase activities) from Thermomyces
      lanuginosus on some rumen fermentation parameters in sheep. Ruminal fluid samples
      were taken just before the morning feeding and then 2 h and 4 h after feeding.
      Xylanase activity, pH, concentration of ammonia and volatile fatty acids were
      measured. The enzyme supplementation did not affect the pH but increased the
      xylanase activity and the total VFA concentration of the rumen fluid. The molar
      proportion of acetate increased, propionate was not affected and butyrate
      decreased after enzyme administration. The concentration of ammonia also
      decreased after supplementation with the enzyme product. It can be concluded that
      the xylanase enzyme preparation from T. lanuginosus induced favourable changes in
      the major rumen fermentation parameters in sheep.

PMID- 17020138
TI  - Influence of the type of management system on corticosterone transfer into eggs
      in laying hens.
AB  - The effect of free-range versus cage management system on corticosterone transfer
      into the eggs was studied in laying hens. Hungarian Yellow laying hens (age: 21
      weeks, body weight: 2.0 +/- 0.5 kg) were divided into two groups in the spring:
      Group I, free-range keeping (n=15 layers, density: > 0.5 bird/m2) in outdoor
      runs, with continuous access to a commercial layer feed; Group II, hens kept in
      battery cages (n=17 layers, density: 2 birds/m2, natural light, continuous access
      to feed and water). Eggs were collected after a one-week adaptation period on
      days 2, 7 and 16. Corticosterone (CST) was extracted from homogenised egg samples
      using an ASE-200 Accelerated Solvent Extractor and then assayed by liquid
      chromatography linked with tandem mass spectrometry (LC-MS/MS) [Thermo Quest
      Surveyor high-performance liquid chromatography (HPLC) interfaced via Atmospheric
      Pressure Chemical Ionisation (APCI) ion source to Finnigan/Thermo Quest LCQ Deca
      MS/MS] using dexamethasone as internal standard with positive APCI ionisation.
      CST concentrations of whole eggs laid by free-range hens on days 2, 7 and 16 were
      0.370 +/- 0.218, 0.259 +/- 0.066 and 0.915 +/- 0.745 ng x g(-1), respectively,
      while those of eggs laid by caged hens were 0.206 +/- 0.157, 0.223 +/- 0.165 and
      0.184 +/- 0.110 ng x g(-1) at the above sampling times. It is concluded that in
      free-range laying hens the sharp changes of environmental weather conditions
      significantly increased the corticosterone content of eggs, while the
      environmentally controlled and closed battery cage management technology resulted
      in relatively uniform corticosterone concentrations in the whole eggs.

PMID- 17020139
TI  - Prevalence and features of canine atopic dermatitis in Hungary.
AB  - Medical records of 600 dogs diagnosed with atopic dermatitis were reviewed and
      evaluated with reference to history, geographical distribution, breed
      predilection, clinical signs and positive reactions to allergens as determined by
      intradermal skin testing (IDT) manufactured by Artuvetrin Laboratories. In 66.6%
      of dogs, the age of onset of atopic dermatitis was between 4 months and 3 years.
      Dogs living in the garden suburb of Budapest were more sensitive to house dust
      mites, fleas and moulds, and dogs from the western part of Hungary were more
      sensitive to weeds than to other allergens (p < 0.01). Positive reactions were
      most common to Dermatophagoides farinae followed by human dander. The breed
      distribution found in the present study was consistent with that reported in the
      literature, except for the breeds Hungarian Vizsla, Pumi, French bulldog,
      Doberman Pinscher and Bobtail which were over-represented among atopic dogs
      compared to the breed distribution of the general dog population of a large city
      in Hungary. Breeds with verified adverse reaction to food were Cocker spaniels,
      French bulldogs, Bullmastiffs, Bull terriers, St. Bernards, Tervurens, West
      Highland White terriers and American Staffordshire terriers (p < 0.05). The
      clinical signs of atopic dermatitis and their occurrence are in accordance with
      the data described in the literature.

PMID- 17020140
TI  - Clinical manifestations of canine babesiosis in Hungary (63 cases).
AB  - Clinical observations of Babesia canis infection in 63 dogs during a 1-year
      period are summarised, demonstrating the pathogenicity of the Babesia strain
      endemic in Hungary. Most patients had babesiosis in the spring and autumn,
      correlating with the seasonal activity of ticks. Male animals appeared in higher
      numbers, probably due to an overrepresentation of outdoor dogs. Uncomplicated
      babesiosis was diagnosed in 32 cases. The disease affected dogs of any age in
      this study. Symptoms were similar to those published from other parts of the
      world: lethargy, fever, splenomegaly, pallor, icterus, haemoglobinuria and
      presence of ticks were the most common observations. Thrombocytopenia,
      lymphopenia and neutropenia were frequent haemogram changes. Imidocarb appeared
      to be highly effective in eliminating the Babesia infection. Thirty-one animals
      demonstrated babesiosis with complications. Most Rottweilers (7/9) developed
      complicated disease. Old age was a risk factor for multiple complications.
      Multiple organ manifestations had poor prognosis. Hepatopathy (44%), pancreatitis
      (33%), acute renal failure (ARF; 31%) and disseminated intravascular coagulation
      (DIC; 24%) were frequent complications, while immune-mediated haemolytic anaemia
      (IMHA; 10%), acute respiratory distress syndrome (ARDS; 6%) and cerebral
      babesiosis (3%) were rarely observed. There was a significant difference between
      the mean age of dogs having uncomplicated disease, babesiosis with a single
      complication and babesiosis with multiple complications (3.4, 4.8 and 8.6 years,
      respectively, p < 0.001). The recovery rate (78, 68 and 25%, respectively, p =
      0.005) and mortality rate (3, 21 and 67%, respectively, p < 0.001) also tended to
      differ significantly in these groups. Systemic inflammatory response syndrome
      (SIRS) and DIC are two possible pathways leading to multiple organ dysfunction
      syndrome (MODS) in babesiosis. DIC was found to predict MODS more sensitively in
      this study than SIRS: there were 6 animals developing MODS out of 11 identified
      with DIC, while only 5 dogs developed MODS out of 22 having SIRS.

PMID- 17020141
TI  - Repeatability and reproducibility of distraction indices in PennHIP examinations
      of the hip joint in dogs.
AB  - Repeatability and reproducibility of Distraction Index (DI) measurements in the
      PennHIP method were evaluated in 100 dogs. The PennHIP distraction views sent to
      the PennHIP Analysis Center (PAC) were duplicated, digitalised, and identified
      with a code, and an adequate computer software was used for DI measurements. One
      examiner performed two DI measurement sessions, evaluating individually 200 hip
      joints. The scoring repeatability and reproducibility were estimated calculating
      the Intraclass Correlation Coefficient (ICC) between the two DI measurement
      sessions and between the second DI measurement session and the DI in PAC reports,
      respectively. The ICC for repeatability was 0.97 [95% confidence interval (CI),
      0.96 to 0.98], and the ICC for reproducibility was 0.95 (95% CI, 0.93 to 0.96).
      The results suggest that the DI measurement method described is repeatable and
      can reproduce the PAC reports with confidence. Distraction indices measured in
      different PennHIP studies, using this DI measurement method and performed by
      trained researchers, can be considered interchangeable.

PMID- 17020142
TI  - Effect of MYOG genotypes on growth rate and production traits in Hungarian large
      white pigs.
AB  - The effect of the porcine myogenin (Myog) 3' polymorphism on birth weight, growth
      rate, carcass weight, lean weight, lean meat percentage and back-fat thickness
      has been investigated in Hungarian Large White pigs. MYOG genotypes were
      determined by PCR-RFLP assay. The obtained MYOGA frequency value was 0.6275. Due
      to the small number of BB piglets the effect of the MYOG genotypes on birth
      weight was not significant; however, an increasing tendency was observed from
      genotype AA to BB. The growth rate difference between MYOG genotypes was
      significant: BB animals showed the highest growth rate values during the
      fattening period. Since few results are available on the possible use of MYOG
      gene polymorphism in selection to improve carcass and growth traits, by this
      study the authors hope to provide additional data on this particular subject.

PMID- 17020143
TI  - Distribution of Toxocara infection in the environment and in definitive and
      paratenic hosts in Estonia.
AB  - The aim of the study was to elucidate the distribution and possible transmission
      routes of Toxocara spp. infection in Estonia. Out of 454 faecal and sand samples
      collected from park lawns and sandpits in the town of Tartu, 19 were Toxocara
      positive (4.2%). Out of the 45 sandpit samples 17.8% were Toxocara positive. Cat
      faeces was found in 21 sandpit samples. Parasitological necropsies were performed
      on 41 euthanised stray dogs and 27 cats in the Tallinn Dog Home. Additionally, 13
      wild free-roaming brown rats (Rattus norvegicus) were captured from the Tallinn
      Dog Home territory, necropsied and studied for the presence of Toxocara larvae.
      Toxocara canis adults were found in 14.6% of the dogs and Toxocara cati (syn.
      mystax) adults in the small intestines of 48.2% of the cats examined. Larval
      infection was detected in the kidney and liver in 5 dogs (12.2%). Our study
      demonstrated only low-level larval Toxocara infections in adult dogs. Toxocara
      larvae were not found in cats and brown rats. According to the results of this
      study, cats more often carry Toxocara infection than dogs. Under our conditions,
      stray and free-roaming cats are the main contaminators of the environment with
      Toxocara eggs. Children playing in sandpits are the main risk group for larval
      toxocarosis.

PMID- 17020144
TI  - First report on Encephalitozoon intestinalis infection of swine in Europe.
AB  - Encephalitozoon intestinalis infection of sows is reported from a pig farm in
      Slovakia. Spores were detected by direct microscopic visualisation in the faeces
      of 25 out of 27 sows (92.6%). This finding was also supported serologically by
      the presence of specific anti-E. intestinalis antibodies and by a species
      specific polymerase chain reaction (PCR). This is the first report on E.
      intestinalis infection of swine in Europe.

PMID- 17020145
TI  - Gh and IGF-I increase leptin receptor expression in prepubertal pig ovaries: the
      role of leptin in steroid secretion and cell apoptosis.
AB  - Leptin (L) is recognised as an important regulator of puberty and a factor which
      controls reproduction. Whole pig ovarian follicles were incubated with different
      doses of leptin (2, 20 and 200 ng/ml) added alone or in combination with 100
      ng/ml of GH or 50 ng/ml of IGF-I. The expression of the functional long form
      leptin receptor (Ob-Rb) mRNA was examined by semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) in follicular cells cultured
      with GH or IGF-I. Both GH and IGF-I increased leptin receptor expression in
      prepubertal pig ovaries. In separate experiments, the action of leptin on ovarian
      follicular steroidogenesis and cell apoptosis was examined. After 24 h of
      incubation with leptin alone or in combination with GH or IGF-I, oestradiol (E2)
      levels were determined in the culture medium while follicular tissue was used for
      the estimation of caspase-3 activity. Leptin increased E2 secretion and
      significantly diminished caspase-3 activity at all doses used. Both GH and IGF-I
      stimulated oestradiol secretion and decreased caspase-3 activity. No differences
      were demonstrable in oestradiol secretion and caspase-3 activity between cells
      treated with GH plus leptin and GH alone or cells treated with IGF-I plus leptin
      as compared to cultures treated with GH or IGF-I alone. However, GH diminished
      leptin-stimulated oestradiol secretion while IGF-I was without effect on it. Both
      GH and IGF-I reversed the anti-apoptotic action of leptin. In conclusion, we
      infer that (1) leptin directly affects ovarian function in prepubertal animals by
      its action on oestradiol secretion and cell apoptosis, (2) GH and IGF-I modulate
      the action of leptin, and (3) at least in part, the direct effect of GH/IGF-I on
      leptin production is due to an action on leptin receptor expression.

PMID- 17020146
TI  - Toxicological mechanisms of Aconitum alkaloids.
AB  - The toxic effects of Aconitum alkaloids are known to affect mainly the central
      nervous system, heart and muscle tissues. Their toxicological mechanisms may
      involve interaction with voltage-dependent Na+ channels, modulation of
      neurotransmitter release and related receptors, promotion of lipid peroxidation
      and induction of cell apoptosis in heart, liver or other organs. Of them, the
      mechanism of interaction with voltage-dependent Na+ channels is quite well known,
      but the other factors are still unclear, and need to be further studied. This
      review focuses on the toxicological mechanisms of Aconitum alkaloids.

PMID- 17020147
TI  - Synthesis and antiproliferative activity in vitro of diacetylenic thioquinolines.
AB  - A series of new acetylenic thioquinolines containing propargyl, 2-butynyl, or 4
      bromo-2-butynyl groups has been prepared and tested for antiproliferative
      activity in vitro against the cells of human [SW707 (colon cancer), CCRF/CEM
      (leukemia)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. All the
      compounds obtained exhibited antiproliferative activity. The most active
      compounds 4h and 41-m have ID50 values ranging from 0.2 to 3.6 microg/ml,
      comparable to that of the reference compound cisplatin.

PMID- 17020148
TI  - Photochemistry of phenazopyridine hydrochloride.
AB  - Phenazopyridine hydrochloride (1) is an azo dye with local analgesic and
      anaesthetic effects on the urinary tract. Its photochemistry was studied in
      different reaction media including the drug adsorbed on silica gel. This resulted
      in photochemical cyclodehydrogenation, reductive photodegradation and
      rearrangement of the drug molecule. Four major products were isolated and
      identified on the basis of IR, NMR and mass spectral studies. The products are:
      pyrido[3,4-c]cinnoline-2,4-diamine (2), N3-phenylpyridine-2,3,4,6-tetraamine (3),
      pyridine-2,3,6-triamine (4), 2,6-diamino-1-(4-aminophenyl)pyridin-4(1H)-one (5).

PMID- 17020149
TI  - Evaluation of monolithic C18 HPLC columns for the fast analysis of pilocarpine
      hydrochloride in the presence of its degradation products.
AB  - Monolithic Performance C18 HPLC columns (Chromolith Performance RP-18e, Merck)
      were applied for the determination of pilocarpine hydrochloride in the presence
      of its degradation products isopilocarpine, pilocarpic acid and isopilocarpic
      acid. The method was validated using a set of six monolithic columns and compared
      to a conventional C18 column. The separation of pilocarpine from its degradation
      products was investigated on monolithic columns at different flow rates from 1 to
      9 ml/min. Superior resolution was obtained using monolithic columns over the
      conventional C18 column at the same flow rate of 1 ml/min with a total run time
      of 9 min compared to 13.5 min for the conventional C18 column. Comparable
      resolution to that obtained in the C18 column (but with better peak symmetry) was
      obtained at a flow rate of 4 ml/min, although the total run time was reduced to
      3.5 min. The precision for both retention time and peak area was investigated
      over a wide concentration range and found to be equal, or slightly better on
      Chromolith Performance compared to the conventional column. The overall RSDs%
      ranged from 0.5% to 1.16% for the conventional column, while for monolithic
      columns ranged from 0.38% to 0.87% at a flow rate of 1 ml/min and from 0.38% to
      0.89% at a flow rate of 4 ml/min. Monolithic column to column reproducibility (n
      = 6) was measured. The RSDs% ranged from 0.34% to 0.68% for retention time and
      from 0.3% to 0.94% for peak areas. The detection and quantitation limits on
      monolithic columns at both flow rates (1 and 4 ml/min) were found to be 0.17
      microg/ml and 0.5 microg/ml, compared to 0.31 microg/ml and 1 microg/ml on the
      conventional column. Monolithic silica rods have also shown the advantage of
      reducing the time to wash and to re-equilibrate the column. The method showed
      good linearity and recovery and was found to be suitable for the analysis of
      pilocarpine hydrochloride formulations.

PMID- 17020150
TI  - A rapid HPLC/ESI-MS method for the quantitative determination of oridonin in rat
      plasma.
AB  - A rapid and accurate method using liquid chromatography with electrospray
      ionization mass spectrometric detection (HPLC/ESI-MS) was developed and validated
      for the determination of oridonin in rat plasma. The analytes were extracted with
      ethyl acetate-n-butyl alcohol (100:2, v/v) after spiking the samples with ethyl
      hydroxybenzoate (internal standard). The separation was carried out on a Diamon
      sil C18 column with an isocratic mobile phase consisting of methanol-water
      (80:20, v/v) at a flow rate of 1.0 ml/min. The lower limit of quantification
      (LLOQ) of the method was 10 ng/ml and the linear range was 10-4000 ng/ml. The
      intra-day and inter-day accuracy and precision of the assay were less than 9%.
      This method has been applied successfully to a preliminary pharmacokinetic study
      involving the intravenous administration of oridonin to rats.

PMID- 17020151
TI  - Electroanalytical determination of donepezil HCl in tablets and human serum by
      differential pulse and osteryoung square wave voltammetry at a glassy carbon
      electrode.
AB  - Donepezil hydrochloride (DNP) is used for the treatment of mild to moderate
      dementia of the Alzheimer's type. The voltammetric behavior of DNP was studied at
      a glassy carbon electrode using cyclic, linear sweep, differential pulse (DPV)
      and square-wave (OSWV) voltammetric techniques. DNP exhibited irreversible anodic
      waves within the pH range 1.80 and 9.00 in different supporting electrolytes. The
      peak was characterized as being irreversible and diffusion-controlled. The
      possible mechanism of the oxidation process is discussed. The current
      concentration plot was rectilinear over the range from 1 x 10(-6) to 1 x 10(-4) M
      in Britton-Robinson buffer at pH 7.0 with a correlation coefficient between 0.997
      and 0.999 in supporting electrolyte and human serum samples using the DPV and SWV
      techniques. The repeatability and reproducibility of the methods for both media
      (supporting electrolyte and serum sample) were determined. Precision and accuracy
      of the developed methods were demonstrated by recovery studies. The standard
      addition method was used for the recovery studies. No electroactive interferences
      were found in biological fluids from endogenous substances or additives present
      in tablets. The methods developed were successfully applied to the determination
      of DNP in tablets and in spiked human serum.

PMID- 17020152
TI  - Stability indicating ultraviolet spectroscopic method for the estimation of
      ezetimibe and carvedilol.
AB  - In this study, new and rapid stability indicating ultraviolet spectroscopic
      methods were developed and validated for the estimation of ezetimibe and
      carvedilol in pure form and in their respective formulations. Since both the
      drugs are poorly water soluble, 20% v/v acetonitrile in triple distilled water
      was selected as the solvent system for both the drugs. This ensured adequate drug
      solubility and maximum assay sensitivity. The linearity range for ezetimibe and
      carvedilol at their respective wavelength of detection of 232 nm and 238 nm was
      obtained as 2-50 microg/ml and 2-20 microg/ml respectively. The linear regression
      equations obtained by least square regression method, were Y = 0.0443 x (X) +
      0.0106 for ezetimibe and Y = 0.1080 x (X) + 0.034 for carvedilol, where Y is the
      absorbance and X is the concentration (in microg/ml) of pure drug solution. The
      detection and quantitation limit as per the error propagation theory were found
      to be 0.4 microg/ml and 1.3 microg/ml respectively for ezetimibe and 0.7
      microg/ml and 2.1 microg/ml respectively for carvedilol. The methods were
      employed with high degree of precision and accuracy for the estimation of total
      drug content in two commercial tablet formulations of each of the two drugs. It
      was concluded that both the developed methods are accurate, sensitive, precise,
      and reproducible. They can be applied directly for the estimation of drug content
      in pharmaceutical formulations.

PMID- 17020153
TI  - Fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) as a model
      protein drug: opportunities and drawbacks.
AB  - In the therapy of various diseases, parenterally administered protein drugs are
      of steadily rising importance. In order to reduce the application frequency,
      these proteins can be incorporated into drug delivery systems, e.g. biodegradable
      microparticles from poly(lactic-co-glycolic acid) (PLGA). To evaluate the
      characteristics of these vehicles, fluorescent labelled proteins like fluorescein
      isothiocyanate labelled bovine serum albumin (FITC-BSA) may be used as model
      drugs to allow the visualisation of the protein localisation within the
      microparticle and the detection of microparticles in cell cultures or tissues.
      However, the quantification of protein by fluorescence spectroscopy failed. In
      this study we focused on the mechanism of fluorescence dequenching in a multi
      FITC-labelled protein and its impact on a reliable protein determination.

PMID- 17020154
TI  - beta-Estradiol biodegradable microspheres: effect of formulation parameters on
      encapsulation efficiency and in vitro release.
AB  - The purpose of this work was to study the effect of organic solvent and
      surfactant type on the in vitro release behavior in general and on the burst
      release in particular of beta-estradiol from PLA/PLGA microspheres. Also the
      effect of these variables on the encapsulation efficiency was investigated. The
      microspheres were prepared by solvent evaporation technique using dichloromethane
      (DCM), ethyl acetate (EtAc), tetrahydrofuran (THF), chloroform (CHCl3) or acetone
      (AC) as organic solvent and polyvinyl alcohol (PVA), Tween 80, sodium lauryl
      sulfate (SLS) or benzalkonium chloride (BKCI) as surfactant. The obtained
      microspheres were tested for encapsulation efficiency and in vitro drug release
      using 50% methanol/buffer pH 7.4 as dissolution medium. EtAC and PVA formulations
      showed the highest encapsulation efficiency and the lowest burst release. These
      microspheres were further characterized for particle size distribution, SEM and
      zeta potential. The results suggested that these materials could be starting
      materials to prepare a beta-estradiol biodegradable controlled delivery system.

PMID- 17020155
TI  - Studies on gynaecological hydrophilic lactic acid preparations, Part 7: use of
      chitosan as lactic acid carrier in intravaginal tablets (globuli vaginales).
AB  - Intravaginal tablets based on hydrophilic methylcellulose and containing lactic
      acid complexed with chitosan undergo deformation under standard conditions. The
      high flow--limit of the gel originating from the tablets as well as its dynamic
      viscosity should ensure the durability of this dosage form on the vaginal mucosa.
      By selecting either ratios of lactic acid to chitosan of 1:1 or 2:1 it is
      possible to obtain tablets that disintegrate into a gel form at pH 3.8-4.4, i.e.
      the pH remains within the physiological range. Increasing the amount of lactic
      acid in the complex in relation to polymer to a 4:1 ratio results in gels with a
      lower pH while giving an acid reserve that can neutralize the excess of alkali
      present in severe vaginal infections.

PMID- 17020157
TI  - Mathematical representation of solubility of amino acids in binary aqueous
      organic solvent mixtures at various temperatures using the Jouyban-Acree model.
AB  - Applicability of a solution model for calculating solubility of amino acids in
      binary aqueous-organic solvent mixtures at various temperatures was shown. The
      accuracy of the proposed model was evaluated by computing mean percentage
      deviation (MPD) employing available solubility data of amino acids in binary
      solvents at various temperatures from the literature. The overall MPD (+/- SD)
      for correlation of solubility data was 16.5 +/- 8.8%. In addition, the equations
      calculating solubility of amino acids in binary solvent mixtures at a fixed
      temperature was revisited.

PMID- 17020156
TI  - Promoting effect of borneol on the permeability of puerarin eye drops and timolol
      maleate eye drops through the cornea in vitro.
AB  - Studies on the influence of borneol on the penetration of puerarin eye drops and
      timolol maleate eye drops through the cornea, and evaluation of the ocular
      irritability were conducted to provide a theoretical basis for the application of
      borneol in enhancing corneal permeability. The cornea penetrative experiment in
      vitro was conducted to observe the quantitative change of puerarin and timolol
      maleate penetrated through the cornea after administering different dosages of
      borneol. The corneal hydration level and blinking frequency were recorded as
      irritability indexes in vitro and in vivo. The steady-flow J of high, middle and
      low dosage groups of puerarin eye drops with borneol were increased by 49%, 32%,
      5% respectively, and permeability parameter Kp increased by 49%, 32%, 5%
      respectively, as compared to that of the control group. The steady-flow J of high
      dosage group of timolol maleate eye drops with borneol was increased by 5%;
      middle and low dosage groups with borneol were decreased by 6%, 3% respectively.
      The permeability parameter Kp of high dosage group increased by 5%, while middle
      and low dosage groups with borneol were decreased by 6%, 3% respectively, as
      compared to that of the control group. Evaluation showed no ocular irritability
      caused by borneol. The results of this study suggest that the promoting effect of
      borneol on the permeability of drugs through the cornea in vitro is selective,
      which indicates that borneol has the potential to be used as an ophthalmic
      penetration enhancer.

PMID- 17020158
TI  - Cardio-protective role of Terminalia arjuna bark extract is possibly mediated
      through alterations in thyroid hormones.
AB  - Terminalia arjuna bark extract is believed to exhibit cardio-protective effects.
      In the present study we investigated the possible involvement of thyroid hormones
      in the amelioration of cardiac and hepatic lipid peroxidation (LPO) by a bark
      extract of the plant in albino rats. While L-thyroxine (L-T4) treatment increased
      the level of thyroid hormones, heart/body weight ratio as well as cardiac and
      hepatic lipid peroxidation, simultaneous administration of 21.42 and 42.84 mg/kg
      of the plant extract decreased the level of thyroid hormones and also the cardiac
      LPO, suggesting the possible mediation of the drug action through an inhibition
      in thyroid function. These effects were comparable to a standard antithyroid
      drug, propyl thiouracil (PTU). When the drug was administered to euthyroid
      animals, serum concentrations of thyroid hormones were decreased, whereas the
      hepatic LPO increased indicating a drug induced toxicity in euthyroid subjects.
      Although a suboptimal dose of the drug was found to be non-toxic to the liver, it
      appeared to be of no use, as it could neither affect the thyroid functions nor
      the cardiac lipid peroxidation. Since in euthyroid animals, thyroid hormones were
      decreased and hepatic LPO was increased, it is suggested that high amounts of
      this plant extract should not be consumed, as hepatotoxicity as well as
      hypothyroidism may be caused.

PMID- 17020159
TI  - Screening of potential chemopreventive compounds from Poncirus trifoliata Raf.
AB  - Chemopreventive agents induce a battery of genes whose protein products can
      protect cells from chemical-induced carcinogenesis. In this study, we isolated
      three different coumarins compounds (1; poncimarin, 2; heraclenol 3'-methyl ester
      and 3; oxypeucedanin methanolate) from Poncirus trifoliata Raf., and studied
      whether these compounds increase glutathione S-transferase (GST) expression and
      activity in the H4IIE cell-line (a rat hepatocyte cell line). CDNB (1-chloro-2,4
      dinitrobenzene; GST subtype-nonspecific) and NBD (7-chloro-4-nitrobenzo-2-oxa-1,3
      diazole; GSTalpha-type-specific) assays revealed that compound 1 most potently
      increased GST enzyme activities. Western blot analysis using subtype-specific
      antibodies confirmed that these three coumarins also selectively increased
      GSTalpha-protein expression, and that compound 1 most actively induced GSTalpha.
      In contrast, the expressions of the GSTmu and GSTmu subtypes were not altered by
      these three coumarins. Reporter gene analysis using an antioxidant response
      element (ARE) containing construct and subcellular fractionation assays, revealed
      that GSTalpha-induction by compound 1 might be associated with Nrf2/ARE
      activation. These results suggest that these three coumarin compounds from
      Poncirus trifoliata Raf possess phase II enzyme inducible functions, and in
      particular, that poncimarin has chemopreventive potential.

PMID- 17020161
TI  - [Detection of phenol by means of 4-aminophenazone according to Emerson].
AB  - In the literature it is reported that 4-(N,N-dimethylamino) phenazone, like 4
      amino phenazone, gives a positive Emerson reaction. This, however, is not true
      and seems to be a misinterpretation due to very similar common names of the
      substances.

PMID- 17020160
TI  - New benzoyl urea derivatives as novel NR2B selective NMDA receptor antagonists.
AB  - A novel series of benzoyl urea derivatives was prepared and identified as NR2B
      selective NMDA receptor antagonists. The influence of the substitution of the
      piperidine ring on the biological activity of the compounds was studied. Compound
      9 was active in the formalin test in mice.

PMID- 17020162
TI  - Characterization of different samples of quercetin in solid-state: indication of
      polymorphism occurrence.
AB  - The present work was designed to compare four commercial samples of quercetin,
      three of them presenting pharmaceutical grade (QPGa, QPGb and QPGc) and the other
      one pro-analysi grade (QPA) by means of different techniques. Physical and
      chromatographic characterization of these samples shows different properties
      following its origin, especially a clear evidence of polymorphism occurrence.

PMID- 17020163
TI  - Pharmacokinetic and bioequivalence testing of atorvastatin formulations in
      healthy male volunteers.
AB  - The aim of this study was to compare the bioavailability of two atorvastatin
      formulations (Divator Drogsan Pharmaceuticals, Ankara, Turkey, as the test
      formulation, and Lipitor, Pfizer Ireland Pharmaceuticals, Dublin, Ireland, as the
      reference formulation) in 52 healthy volunteers. The study was conducted using a
      randomised, single-dose, two-way crossover study with a 2-week washout period
      between the doses. Since the 90% confidence intervals for Cmax, AUC0-72 and AUC0
      proprtional to ratios for both, the parent atorvastatin and its main active
      metabolite ortho-hydroxy atorvastatin, were within the pre-defined Bioequivalance
      acceptance limits approved by EMEA, we concluded that the atorvastatin
      formulation elaborated by Drogsan Pharmaceuticals, was bioequivalent to the
      Lipitor in its rate and extent of absorption.

PMID- 17020164
TI  - Protective effect of simvastatin and VULM 1457 in ischaemic-reperfused myocardium
      of the diabetic-hypercholesterolemic rats.
AB  - This study examined the effects of simvastatin (10 mg/ kg) and VULM 1457 (50
      mg/kg), an ACAT inhibitor, in the heart model of 6 min ischemia followed by 10
      min reperfusion injury in the diabetic-hypercholesterolaemic (DM-HCH) rats. In
      the DM-HCH rats, the incidence of ventricular tachycardia (VT) had a tendency to
      be increased, while ventricular fibrillation (VF) occurred in all diseased rats
      (p < 0.01). Simvastatin and VULM 1457 with the shown hypolipidemic effect,
      significantly (p < 0.01) suppressed a formation of VF (38% and 29%;
      respectively).

PMID- 17020165
TI  - A new cyclotetrapeptide from marine fungus Trichoderma reesei.
AB  - A new cyclotetrapeptide, trichoderide A, was isolated from the marine fungus
      Trichoderma reesei. The structure was identified by spectral methods, and the
      stereochemical assignments were made by chiral HPLC of the hydrolyzed compound.
      Trichoderide A showed moderate cytotoxity against human A375-S2 melanoma cell
      line.

PMID- 17020166
TI  - Two new triterpenoids from the carpophore of Xanthoceras sorbifolia Bunge.
AB  - Two new triterpenoids 3-O-beta-d-glucopyranosyl (1-->6)-beta-d-glucopyranosyl, 28
      O-beta-d-glucopyranosyl (1-->6) [alpha-l-rhamnopyranosyl (1-->2)]-beta-d
      glucopyranosyl, 16-deoxybarringtogenol C (1) and 22-O-acetyl-21-O-(4'-O-angeloyl)
      beta-d-fucopyranosyl theasapogenol B (2), were isolated from the dried carpophore
      of Xanthoceras sorbifolia Bunge (Sapindaceae). 1 and 2 were found to have
      activity of inhibiting the proliferation of two human tumor cell lines.

PMID- 17020167
TI  - A new lignan from Smilax bockii warb.
AB  - A new lignan named (-)-isolariciresinol 9'-carboxylic acid methyl ester has been
      isolated from the roots of Smilax bockii warb. The structure of the new lignan
      was determined on the basis of spectral and chemical studies.

PMID- 17020168
TI  - Commercialism in dentistry and its victims.

PMID- 17020169
TI  - We are long overdue for a change in the way we do business.

PMID- 17020170
TI  - Early statement of purpose.

PMID- 17020171
TI  - Commission on journalism.

PMID- 17020172
TI  - Reporting policy through the Journal of the American College of Dentists.

PMID- 17020173
TI  - The mace and torch.

PMID- 17020174
TI  - Research Institute.

PMID- 17020175
TI  - Survey of dental students.

PMID- 17020176
TI  - Ethics and professionalism: the past, present, and future.
AB  - A retrospective look at the history of medicine is highlighted by the
      relationship of trust and service that characterize the professions. This
      foundation for ethics is being challenged today by forces such as the rapid
      growth of managed care, the liberalized regulations on professional advertising,
      and the emergence of a better-informed public that is far less inclined to accept
      a doctor's recommendation as the final word. While acknowledging a changing
      reality, dentistry--individually and collectively--must re-establish the primacy
      of ethics as the touchstone of professionalism.

PMID- 17020177
TI  - Performance.
AB  - High performance is difficult to maintain because it is dynamic and not well
      understood. Based on a synthesis of many sources, a model is proposed where
      performance is a function of the balance between capacity and challenge. Too much
      challenge produces coping (or a crash); excess capacity results in boredom. Over
      time, peak performance drifts toward boredom. Performance can be managed by
      adjusting our level of ability, our effort, the opportunity to perform, and the
      challenge we agree to take on. Coping, substandard but acceptable performance, is
      common among professionals and its long-term side effects can be debilitating. A
      crash occurs when coping mechanisms fail.

PMID- 17020178
TI  - Partnerships support ACHE services. Corporate relationships continue to grow as
      program matures.

PMID- 17020179
TI  - Interview witfi ACHE's incoming chairman. Interview by Marilyn E Mages.

PMID- 17020180
TI  - Make safety a priority. Create and maintain a culture of patient safety.

PMID- 17020181
TI  - Patient safety: engaging medical staff toward a common goal.

PMID- 17020182
TI  - After the storm: experiences and insights from the front.
AB  - You can never totally prepare for a disaster. However, from each occurrence we
      learn new lessons and gain insight to the preparations, collaborative strategies
      and flexible tactics needed to respond effectively. The scenarios below are a
      small sampling of what ACHE affiliates dealt with in the wake of Hurricanes
      Katrina and Rita. The leaders of these healthcare organizations know the
      importance of having a comprehensive disaster plan, adapting to the situation you
      face and stepping back to evaluate and make adjustments for the future.

PMID- 17020183
TI  - The value of an ethics audit. An ethics audit can help identify and address
      problems with an organization's ethical culture.

PMID- 17020184
TI  - Building a better Web site. A case study in cohesiveness.

PMID- 17020185
TI  - Volunteers in medicine. Help the uninsured in your community.

PMID- 17020186
TI  - A foggy crystal ball. The federal health policy agenda for 2006.

PMID- 17020187
TI  - Ability job-fit self-assessment. Employment considerations for job seekers.

PMID- 17020188
TI  - Quality and patient safety. Engaging your board to take the lead.

PMID- 17020189
TI  - Starting a corporate college. New York Hospital Queens creates a model for
      continuous learning.

PMID- 17020190
TI  - Creating a green healing environment. How PMC found a way to increase patient
      satisfaction.

PMID- 17020191
TI  - Member needs and affiliate survey. Convenience and content rank high.

PMID- 17020192
TI  - Summer mentoring memories.

PMID- 17020193
TI  - An analysis of IEEE publications in biomedical engineering.

PMID- 17020194
TI  - Not an undergraduate anymore? EMBS cares.

PMID- 17020195
TI  - MEMS in medicine and biology.

PMID- 17020196
TI  - Therapeutic technologies in neuroengineering.

PMID- 17020197
TI  - Sensors for brain-computer interfaces.

PMID- 17020198
TI  - Passing data and supplying power to neural implants.

PMID- 17020199
TI  - Silicon LSI-based smart stimulators for retinal prosthesis.

PMID- 17020200
TI  - Intraocular retinal prosthesis. Big steps to sight restoration.

PMID- 17020201
TI  - Image-guided neurosurgery at Brigham and Women's Hospital.

PMID- 17020203
TI  - The strategic impact of revised DRG payments.

PMID- 17020202
TI  - Electrical stimulation as therapy for neurological disorder.

PMID- 17020204
TI  - CMS bows to popular demand, rolls back some Medicare cuts.

PMID- 17020205
TI  - Taking a pulse: Three institutions making strides in healthcare information
      technology.

PMID- 17020206
TI  - Standardized survey helps hospitals gauge service, improve quality.

PMID- 17020207
TI  - Five steps for getting the most out of employee benefit plans.

PMID- 17020208
TI  - Leadership turnover: don't lose sight of market strategy when a new CEO takes the
      helm of your healthcare organization.

PMID- 17020209
TI  - Analysis of factors that affect responding in a two-response chain in children
      with developmental disabilities.
AB  - A sequence of behaviors consisting of appropriate responses, inappropriate
      responses, or a combination of both can be linked together in a behavior chain.
      Several operant processes may disrupt behavior chains. For example, one or more
      members of the behavior chain may be affected when reinforcement is withheld for
      the last response in the chain (extinction), when the last response is reinforced
      even if it occurs without the other responses in the chain (unchaining), or when
      access to the terminal reinforcer is available independent of responding
      (satiation). However, few studies have examined the effects of these types of
      procedures on responding that occurs in the context of behavior chains. The
      purpose of this study was to examine the effects of three clinically relevant
      procedures and processes (i.e., extinction, satiation, and unchaining) on
      behaviors that occur as part of a behavior chain. Overall, extinction and
      satiation resulted in a decrease in both responses in the chain. During the
      unchaining procedure, decreases were observed in the first response in the chain
      but not in the second response.

PMID- 17020210
TI  - The generalized matching law in elite sport competition: football play calling as
      operant choice.
AB  - A mathematical model of operant choice, the generalized matching law was used to
      analyze play-calling data from the 2004 National Football League season. In all
      analyses, the relative ratio of passing to rushing plays was examined as a
      function of the relative ratio of reinforcement, defined as yards gained, from
      passing versus rushing. Different analyses focused on season-aggregate data for
      the league as a whole, game-by-game data for the league as a whole, and game-by
      game data for individual teams. In all analyses except those for a few individual
      teams, the generalized matching law accounted for a majority of variance in play
      calling. The typical play-calling pattern reflected undermatching (suggesting
      imperfect sensitivity of play calling to yardage-gained reinforcers) and a bias
      for calling rushing plays. Bias was found to be a function of both the relative
      risk of turnovers and the relative variability in yards gained associated with
      passing versus rushing plays. The external validity of the matching analyses was
      supported by significant correlations between parameters of the generalized
      matching law and team success on offense and season winning percentage. These
      results illustrate the broad applicability of the generalized matching law to
      problems outside of the laboratory.

PMID- 17020211
TI  - Transformations of mathematical and stimulus functions.
AB  - Following a pretest, 8 participants who were unfamiliar with algebraic and
      trigonometric functions received a brief presentation on the rectangular
      coordinate system. Next, they participated in a computer-interactive matching-to
      sample procedure that trained formula-to-formula and formula-to-graph relations.
      Then, they were exposed to 40 novel formula-to-graph tests and 10 novel graph-to
      formula tests. Seven of the 8 participants showed substantial improvement in
      identifying formula-to-graph relations; however, in the test of novel graph-to
      formula relations, participants tended to select equations in their factored
      form. Next, we manipulated contextual cues in the form of rules regarding
      mathematical preferences. First, we informed participants that standard forms of
      equations were preferred over factored forms. In a subsequent test of 10
      additional novel graph-to-formula relations, participants shifted their
      selections to favor equations in their standard form. This preference reversed
      during 10 more tests when financial reward was made contingent on correct
      identification of formulas in factored form. Formula preferences and
      transformation of novel mathematical and stimulus functions are discussed.

PMID- 17020212
TI  - Refining the experimental analysis of academic skills deficits: part II. Use of
      brief experimental analysis to evaluate reading fluency treatments.
AB  - The technology of brief experimental analysis is just beginning to be used for
      identification of effective treatments for individual students who experience
      difficulty with oral reading fluency. In this study, the effect of a reading
      fluency treatment package was examined on easy and hard passages, and
      generalization was assessed on passages with high content overlap. The results
      suggest that the treatment package increased reading fluency for all 3 students.
      Effects were moderated by difficulty level for all 3 students. Results are
      discussed in terms of future refinements to the procedures, validation of the
      methods, and potential applications in clinical and school settings.

PMID- 17020213
TI  - Using telemedicine to conduct behavioral assessments.
AB  - We describe the use of telemedicine by the Biobehavioral Service at the
      University of Iowa Hospitals and Clinics to conduct brief functional analyses for
      children with developmental and behavioral disorders who live in rural areas of
      Iowa. Instead of being served at our outpatient facility, participants received
      initial behavioral assessments in their local schools or social service agencies
      via videoconference. Case descriptions for 2 participants whose evaluations were
      conducted via telemedicine, and a brief summary of all outpatient assessments
      conducted over a 4-year period by the Biobehavioral Service, are provided. This
      report extends previous applications of functional analysis procedures by
      examining brief behavioral assessments conducted via telemedicine.

PMID- 17020214
TI  - Active prompting to decrease cell phone use and increase seat belt use while
      driving.
AB  - Automobile crashes are the leading cause of death for those aged 3 to 33, with
      43,005 (118 per day) Americans killed in 2002 alone. Seat belt use reduces the
      risk of serious injury in an accident, and refraining from using a cell phone
      while driving reduces the risk of an accident. Cell phone use while driving
      increases accident rates, and leads to 2,600 U.S. fatalities each year. An active
      prompting procedure was employed to increase seat belt use and decrease cell
      phone use among drivers exiting a university parking lot. A multiple baseline
      with reversal design was used to evaluate the presentation of two signs: "Please
      Hang Up, I Care" and "Please Buckle Up, I Care." The proportion of drivers who
      complied with the seat belt prompt was high and in line with previous research.
      The proportion of drivers who hung up their cell phones in response to the prompt
      was about equal to that of the seat belt prompt. A procedure that reduces cell
      phone use among automobile drivers is a significant contribution to the
      behavioral safety literature.

PMID- 17020215
TI  - Modification of slot-machine preferences through the use of a conditional
      discrimination paradigm.
AB  - The present experiment investigated the impact of contextually trained
      discriminations on gambling behavior. Nine recreational slot-machine players were
      initially exposed to concurrently available computerized slot machines that were
      each programmed on random-ratio schedules of reinforcement and differed only in
      color. All participants distributed responding equally across the two slot
      machines. A conditional discrimination procedure was then used to teach the
      contextual cues representing the arbitrary relations of "greater than" and "less
      than." Following contextual cue training, participants were reexposed to the
      concurrent slot-machine task. After training of the contextual cues, a higher
      proportion of responses were made to the slot machine that shared formal
      properties (i.e., color) with the contextual cue representing "greater than."

PMID- 17020216
TI  - The effects of undergarment type on the urinary continence of toddlers.
AB  - There is a growing trend toward later toilet training of typically developing
      children. This trend is a problem for caregivers and professionals who work with
      young children, because it is associated with a number of costs and health risks
      in child-care settings. Results of a recent study (Tarbox, Williams, & Friman,
      2004) suggest that wearing underwear may facilitate the development of toileting
      skills. Based on these findings, we examined the effects of wearing disposable
      diapers, disposable pull-on training pants, and underwear on urinary continence
      of 5 typically developing toddlers in a child-care setting. Underwear decreased
      incontinence and increased continent urinations for 2 of the 5 participants,
      produced no improvement in 2 participants, and when combined with increased fluid
      intake and longer sitting periods, produced some favorable trends for the 5th
      participant.

PMID- 17020217
TI  - The effects of varying levels of treatment integrity on child compliance during
      treatment with a three-step prompting procedure.
AB  - The effects of three levels of treatment integrity (100%, 50%, and 0%) on child
      compliance were evaluated in the context of the implementation of a three-step
      prompting procedure. Two typically developing preschool children participated in
      the study. After baseline data on compliance to one of three common demands were
      collected, a therapist implemented the three-step prompting procedure at three
      different integrity levels. One integrity level was associated with each demand.
      The effects of the integrity levels were examined using multielement designs. The
      results indicate that compliance varied according to the level of treatment
      integrity that was in place.

PMID- 17020218
TI  - Experimental analysis and treatment of multiply controlled problem behavior: a
      systematic replication and extension.
AB  - We evaluated interventions designed to reduce multiply controlled problem
      behavior exhibited by a young boy with developmental disabilities, using a
      multiple baseline design. Each intervention was designed to address a specific
      social function of problem behavior. Results showed that the separate
      interventions were useful in reducing problem behavior, and terminal schedules
      were reached by way of schedule thinning (attention condition) and delays to
      reinforcement (tangible and escape conditions).

PMID- 17020219
TI  - A paradoxical effect of presession attention on stereotypy: antecedent attention
      as an establishing, not an abolishing, operation.
AB  - Previous studies have shown that presession attention for problem behavior can
      serve as an abolishing operation when attention functions as a positive
      reinforcer. In the current study, we show that the stereotypy of a child with
      severe disabilities was undifferentiated during standard analogue functional
      analysis conditions. However, when noncontingent presession attention was
      provided, stereotypy occurred for social attention as a positive reinforcer,
      suggesting that the antecedent manipulation functioned as an establishing
      operation.

PMID- 17020221
TI  - Increasing fiction writers' productivity through an internet-based intervention.
AB  - Ten participants from an online community of fiction writers were exposed to a
      treatment package intended to increase their writing productivity. The package
      consisted of graphic feedback provided through a Web page, praise for goal
      completion delivered via e-mail, and editing of manuscripts by other members of
      the community dependent on the completion of word-count goals. A multiple
      baseline design across groups was used to evaluate the effects of the
      intervention, which was successful in increasing the number of words written.

PMID- 17020220
TI  - Behavioral interventions to improve performance in collegiate football.
AB  - Using a multitreatment withdrawal design, this study evaluated the differential
      effects of publicly posted plus verbal feedback, goal setting plus verbal
      feedback, and publicly posted feedback, verbal feedback, and goal setting
      together on the performance of 3 collegiate football players in practice
      scrimmages. Also assessed was whether the changes in practice behavior
      generalized to games. The dependent variables were performances on three wide
      receiver skills. The results show that public posting with verbal feedback, goal
      setting, and public posting with verbal feedback and goal setting were effective
      in improving player performance to a 90% criterion level during practice, and
      these changes generalized to game performance.

PMID- 17020222
TI  - Using reinforcer pairing and fading to increase the milk consumption of a
      preschool child.
AB  - The present study replicates and extends previous research on the treatment of
      food selectivity by implementing pairing and fading procedures to increase a
      child's milk consumption during regularly scheduled preschool meals. The
      treatment involved mixing a small amount of chocolate syrup into a glass of milk
      and gradually eliminating the chocolate. The procedure and data collection were
      implemented by preschool teachers and resulted in increased milk drinking at
      school, which was maintained at home.

PMID- 17020223
TI  - Positive reinforcement according to Maimonides, the 12th century Jewish
      philosopher.

PMID- 17020224
TI  - [Image of the month. Diabetes in an adult revealed by ecthyma ].

PMID- 17020225
TI  - [How I treat....corns and callosities].
AB  - Corns and callosities are the expression of a peculiar aspect of mecanobiology of
      the foot. They are more frequent with ageing, particularly in women. These
      lesions represent a risk factor for the diabetic foot. Prevention measures are
      important to follow in predisposed individuals. Several medicinal and non
      medicinal treatments have proven their efficacy.

PMID- 17020226
TI  - [Idiopathic retroperitoneal fibrosis: unusual cause of abdominal pain. A case
      report].
AB  - Retroperitoneal fibrosis is an uncommon inflammatory disease which is
      characterized by the development of a fibrous process that surrounds the major
      vessels and organs located within the retroperitoneum. Isolated as an idiopathic
      expression or associated with several other diseases in its secondary form,
      retroperitoneal fibrosis remains relatively of rare occurrence and as a result,
      is devoid of either diagnostic or therapeutic definitive recommendations. We
      report the observation of one case admitted in the emergency room for abdominal
      pain induced by left hydronephrosis. Radiographic exploration with contrast
      enhanced studies evidenced retroperitoneal fibrosis causing left ureteric
      obstruction. Therapeutic approach was based on corticosteroids and ureteral
      drainage which prevented recurrence while fibrosis was almost reversed six months
      later.

PMID- 17020227
TI  - [Clinical case of the month. Cerebrovascular accident related to arterial
      brachiocephalic trunk stenosis].
AB  - The authors report the case of a 47-year old man, admitted for syncope and left
      sided motor deficit. Diagnostic investigations revealed a right middle cerebral
      artery embolic stroke, secondary to a critical stenosis of the arterial
      brachiocephalic trunk, harboring a floating thrombus. The treatment options for
      occlusive lesions of the brachiocephalic trunk are discussed, as well as the
      optimal delay between stroke and brain revascularization.

PMID- 17020228
TI  - [Clinical case of the month. Turner's syndrome and aortic dissection].
AB  - A patient, born in 1961, is hospitalised for pubic abdominal pain with
      irradiation to the right and left sides. She has a Turner's syndrome. At first
      evaluation, an abdominal tomography demonstrates a right pyelonephritis. The
      patient is treated with quinolones and she evolves favourably, except that she
      continues to present some abdominal pain. She leaves the hospital, but because of
      permanent abdominal pain, a new abdominal tomography is performed: an aortic
      dissection type B for (Stanford), or III anterograde for (De Bakey), is
      diagnosed. Cardiovascular anomalies are frequent in Turner's syndrome. Aortic
      dissection is a rare complication. Histological analysis shows a cystic medial
      necrosis. Medical and cardiological follow-up is needed.

PMID- 17020229
TI  - [Pulmonary arterial hypertension due to COPD].
AB  - In this paper we review the current knowledge on pulmonary hypertension (PH)
      occurring in COPD. PH is defined as a mean pulmonary arterial pressure at rest
      greater than 20 mmHg measured by right heart catheterisation. PH is usually
      present during exercise before appearing at rest. PH in COPD increases the risk
      of hospitalisation and darkens the disease prognosis. Chronic hypoxemia is the
      major contributor to PH, but remodelling of arterial wall and mechanical factors
      such as hyperinflation also play a role. Transthoracic echocardiography is the
      most useful non invasive investigation, but right heart catheterisation is
      necessary to ascertain the diagnosis. Long term 02 supplementation is the basis
      of the treatment while vasodilatators may worsen hypoxemia.

PMID- 17020230
TI  - [Tall stature: some classical syndromes].
AB  - We describe the findings of XYY syndrome in the setting of encountering an
      individual with this particular condition in the endocrinology clinic. XYY
      syndrome is a relatively frequent if unfamiliar condition, which is characterized
      by taller than average height. The extra Y chromosome may play a role in
      determining the height of these individuals. From this case, a differential
      diagnosis of tall stature is outlined, in addition to a description of the
      principal syndromes associated with gigantism. These primarily include
      Klinefelter syndrome, Marfan syndrome, androgen resistance and growth hormone
      excess. These various entities are described from the point of view of their
      symptomatology, biology, pathophysiology and therapeutic characteristics.

PMID- 17020231
TI  - [Value of the "Bacterial Meningitis Score" (BMS) for the differential diagnosis
      of bacterial versus viral meningitis].
AB  - The "Bacterial Meningitis Score" (BMS) has been designed to identify children at
      low (BMS = 0) or high (BMS > or = 2) risk of bacterial meningitis (M). Its
      calculation is simple; it is based on 5 different items: Gram stain, seizure at
      or before presentation, peripheral white blood cell count (WBC), cerebrospinal
      fluid (CSF) WBC and CSF protein concentration. As of today, it has been validated
      in one single study in the United States. The purpose of this study is to
      evaluate the BMS performance in children hospitalized for M over a 5 years
      period. The medical records of 277 patients diagnosed with M, aged 29 days to 15
      years and hospitalized in the Department of Pediatrics of the CHR Citadelle
      Hospital in Liege between 1999 and 2003 were analysed. Among the 277 hospitalised
      cases, there were 29 bacterial (10,5%) and 248 viral (89,5%) M. For patients
      whose BMS < 2, we found 100% of viral M. For those with BMS > or = 2, 59,3% had a
      bacterial M and 40,7% had a viral M. 23% of the children with BMS < 2 were
      treated with antibiotics; 17% of children with BMS = 2 were not been treated on
      admission. The BMS is an easily applicable method that could allow reduce the
      unnecessary use of antibiotics.

PMID- 17020232
TI  - [Physicians and the danger of nuclear war].
AB  - International Physicians for the Prevention of Nuclear War (IPPNW), the 1985
      Nobel Peace Prize winners, are active in some sixty different countries. Their
      action is based on the outlook that any nuclear war would cause not only millions
      of deaths, but also millions of severely injured or burnt victims for whom the
      medical profession, decimated as well, would be most helpless. They strive to
      obtain that governments, in agreement with treaties that almost all countries
      have signed, ascertain that nuclear weapons, which are internationally illegal,
      be globally abolished. The impact on political authorities would undoubtedly be
      reinforced if the number of physicians supporting the action of IPPNW was
      increased.

PMID- 17020233
TI  - [Necrobiosis lipoidica - 3 case reports].
AB  - Necrobiosis lipoidica is a rare degenerative disease mostly seen on the legs. The
      association to diabetes mellitus is usual. We report three patients with
      necrobiosis lipoidica located on the extremities, 2 of them were already treated
      for diabetes. Necrobiosis lipoidica has distinctive clinical and histological
      appearances. The lesions appear as well circumscribed, erythematous plaques, with
      a depressed centre. Some of these lesions may progress to ulcers. The legs are
      commonly involved. Angiopathy leading to thrombosis of the cutaneous vessels has
      been implicated in its pathogeny. There is no specific therapy for this disease
      Topical and/or intralesional corticosteroids are the most widely used treatment.

PMID- 17020234
TI  - [Prader-Willi syndrome: specific management by a multidisciplinary team].
AB  - Prader Willi syndrome can be viewed as a physiopathological model of obesity.
      Such patients deserve specific management, preferably in a multidisciplinary
      setting. The paper reports on 6 patients followed in the paediatric endocrine
      service at the University of Liege.

PMID- 17020235
TI  - [How I prevent...exacerbation of atopic dermatitis].
AB  - Atopic dermatitis is under the influence of series of environmental factors. The
      contact with unsuited cleaning agents and rough textiles can exacerbate pruritus
      and inflammation. Preventive and adjuvant measures can thus help the care
      procedures of the disease. Appropriate hygiene measures and the use of emollients
      are particularly helpful. Clothing measures are also in place. Undergarments and
      pyjamas made of knitted natural silk are available. Other measures, sometimes
      corresponding to anecdotal claims--antihistamines, thermal cures, unconventional
      medicine, probiotics, chinese herbals, essential fatty acids--have not proven
      their preventive efficacy in atopic dermatitis.

PMID- 17020236
TI  - [Ethics education in nursing students (Belgium)].

PMID- 17020237
TI  - [Technoscience: from the word origin to its actual uses].

PMID- 17020238
TI  - [Impact of educational care in the patient with chronic coronary insufficiency].
AB  - The study which follows is prospective, qualitative and comparative. It relates,
      in first part, to the evaluation of the comprehension of the disease and the
      treatment then change of the practices of life of a population reached of chronic
      cardiac insufficiency. The results show a certain effectiveness of the meetings
      of therapeutic education and an assumption of responsibility coordinated in
      network. The second part tries to include understand the incorporation of this
      new knowledge and led by comparing two groups of men resulting from different
      socio-professional mediums. Research points the importance of the culture of the
      body in the interpretation and the mobilization of the new knowledge obtained on
      pathology and the treatment, the experiment of the body limits, the interactions
      with the professionals of health.

PMID- 17020239
TI  - [Affective touch and self esteem in the elderly].
AB  - The hospital is an environment which accomodates the elderly persons and in which
      these last have to make trainings at one time when they are not in full
      possession with all their physical, psychological and cognitive capacities. They
      can then live there humiliating situations which generate feelings of discomfort,
      embarrassment and shame. The presence of interveners not very warm, lacking
      compassion lack and impressed negative prejudices towards the elderly patients,
      is another factor which is added to lead them not to feel at ease, involving,
      inter alia, consequences a fall of their self-esteem. However the affective touch
      is a strategy which would have the potential to act on the personal value of the
      elderly patients and to thus improve their self-esteem. It is with a view to
      popularize the use of the affective touch in practice nurse that a study was
      carried out in order to check its effects on the self-esteem of the elderly
      patients. The results confirm that the emotional touch influences positively the
      self-esteem of the elderly patients. The authors of the study thus recommend the
      systematization of the affective touch in nursing practice.

PMID- 17020240
TI  - [End of life conflicts in palliative care: a systematic review of the
      literature].
AB  - To evaluate the extent and the quality of the research related to End of life
      conflicts in palliative care from 1995 to 2004. Accessible Literature of several
      electronic data bases (BDSP, Cinhal, Cochrane, Francis, Medline, Psychinfo,
      Saphir, Scopus and Web of science) as well as the grey literature. Studies
      published in French and English between 1995 and 2004 reporting end of life
      conflicts, tensions, disagreements, disputes in the context of palliative care.
      One hundred and two studies were included (87.2% published in English, 12.8% in
      French). Study designs include revues 27.4%), cross-sections 18.6% and case
      studies 18.6%. Reported conflicts are related to ethical issues 26.2%, to care
      19.1%, to tensions between professionals and patients or families 11.1%, to team
      experiences 9%. Six studies 5.8% give prevalence figures of conflicts. Half of
      the studies 51.3% identify possible causes of conflicts: communication issues,
      euthanasia and suicide assistance demands, autonomy of patients, non respect of
      advance directives, cultural differences. Ten studies 9.8% identify specifically
      some effects of the conflicts: moral distress of patients; stress, burn out and
      guilt of health professionals; lack of trust between doctors and patients or
      families. Conflicts are mainly resolved through mediation and ethical
      discussions. Research data on end of life conflicts is scarce at all levels
      (quantity, quality, methods, social impact, and epistemology). A better
      understanding of end of life conflict might foster a more adequate management of
      difficult situations and ultimately a more peaceful death of patients, mourning
      of families and every day work of health professionals

PMID- 17020241
TI  - [End of life conflicts: perceptions of health professionals in French speaking
      Valais].
AB  - The aim of the study was to identify the perception health professionals in
      palliative care had of end of life conflicts. The nature of t he conflicts,their
      prevalence, intensity, causes andeffects were specially addressed. Furthermore
      proposals of possible solutions of conflicts were investigated. A cross-sectional
      study was done through a self-administered questionnaire among 460 health
      professionals in the French Speaking Valais. The health professionals worked
      either in acute care hospitals, chronic health institutions, and old people
      nursing homes or in ambulatory palliative care units. Among the target population
      233 persons replied to the questionnaire (50.6%). Among the respondents 82.4%
      reported to be confronted to end of life conflicts. Conflicts were quite rare
      (66%) and of medium or high intensity (86%). Conflicts were of medical nature
      (74%) or related to ethic issues (64%). Conflicts occurred among family members
      (68%), medical doctors and nurses (49%) or patients et medical staff (16%).
      Conflicts were due mainly (50-60%) to lack of communication, ambivalence among
      parties, differences in value systems. Mentioned (50-60%) consequences of
      conflicts were the waste of resources, the physical and the psychological
      burnout. Possible identified solutions to conflicts were interdisciplinary
      seminars, internal supervision procedure and the sharing of experiences. Neither
      age, nor gender, professional experience, working par place, training were
      predictive of exposure toconflicts. End of life conflicts are a common reality.
      They may compromise the quality of care and may contribute to high economic and
      social costs. They should be put on the public health agenda as a high priority.

PMID- 17020242
TI  - [Characteristics of patient aggression in a psychiatric hospital in Switzerland].
AB  - Characteristics of patient aggression in a psychiatric hospital in Switzerland
      Patient aggression in psychiatry is a prominent problem for all concerned. In
      this prospective survey we registered and analysed all violent incidents of
      patients in a cantonal psychiatric hospital in Switzerland in order to determine
      the characteristics of aggression. The Staff Observation Aggression Scale Revised
      (SOAS-R) was utilised. During the study period 815 patients were admitted to the
      hospital. 71 (63.4%) of the 110 violent incidents were perpetrated by male
      patients. The majority of aggressive incidents were perpetrated in the vicinity
      of the rooms of the patients and were triggered mainly by the refusal to adhere
      to the demands of the patient or by patients' use of toxic substances. The most
      frequent type of aggression was of a verbally aggressive nature and the principal
      target was nursing personnel who felt threatened in most of the cases. In order
      to terminate the aggression the most predominant measure was communication with
      the patient and coercive measures. This study demonstrates clearly that
      aggression concerns psychiatric nursing personnel and points to the
      recommendation to reinforce measures of security and to predictive measures to
      ameliorate the management of aggression.

PMID- 17020243
TI  - [Bedside learning, characteristics and challenges of education in work situations
      of the hemodialysis nurse].
AB  - This clinical exploratory research relates to the situation of the professional
      graduate male nurse who, within the framework of the continuous training profits
      from a formation of a few weeks at all formalized in a center of hemodialysis.
      The analysis of the directing semi talks carried out near dialysed patients,
      formative male nurses and learning male nurses, could highlight the
      characteristics of the actors of this situation of on-the-job training, the
      general aspects of this formation, the object and stakes of the training as well
      as the facilitating and blocking factors. The taking into account of these
      elements allowed certain recommendations as regards training scheme and to define
      the role of the framework of health in the setting in of this program. It also
      made it possible to question the relational training through this situation of
      formation which mixes three othernesses: learning and its tutor, but also the
      dialysed patient touched in his flesh by the object of training and shown that
      the relational competence developed in the care enriches relational competences
      in andragogy and conversely.

PMID- 17020244
TI  - Temperature dependence of the optical rotation of fenchone calculated by
      vibrational averaging.
AB  - On the basis of vibrational averaging, the temperature dependence of the optical
      rotation for fenchone has been calculated using TDDFT with the B3LYP hybrid
      functional at three wavelengths. The results show that very good agreement is
      obtained between theory and experiment. It is concluded that temperature
      dependent vibrational effects are likely to account for much of the observed
      temperature dependence in optical rotation exhibited by rigid organic molecules
      in case there is only a weak temperature-dependent interaction with the solvent.

PMID- 17020245
TI  - Interferometric coherence transfer modulations in triply vibrationally enhanced
      four-wave mixing.
AB  - Triply vibrationally enhanced (TRIVE) four-wave mixing (FWM) spectroscopy in a
      mixed frequency/time domain experiment contains new output coherences that
      isolate nonlinear pathways that involve coherence transfer. Coherence transfer
      occurs when a thermal bath induces coupling between two states so a quantum
      mechanical entanglement of a pair of quantum states evolves to entangle a new
      pair of quantum states. The FWM includes several equivalent coherence pathways
      that interfere and create a temporal modulation of the output coherence that is a
      signature of coherence transfer. The transfer shifts the output coherence
      frequency and isolates coherence transfer pathways from the stronger FWM
      processes that form the basis of coherent multidimensional spectroscopy. The use
      of coherence transfer offers the opportunity for another form of coherent
      multidimensional spectroscopy where cross-peaks appear because of the coherence
      transfer between quantum states. Since this approach is based on frequency domain
      methods, it requires only short-term phase coherence during the excitation
      process so the method is not constrained to accessing the quantum states lying
      within the excitation pulse bandwidth.

PMID- 17020246
TI  - Search space mapping: getting a picture of coherent laser control.
AB  - Search space mapping is a method for quickly visualizing the experimental
      parameters that can affect the outcome of a coherent control experiment. We
      demonstrate experimental search space mapping for the selective fragmentation and
      ionization of para-nitrotoluene and show how this method allows us to gather
      information about the dominant trends behind our achieved control.

PMID- 17020247
TI  - Metastable intermolecular charge-transfer complexes with a pentavalent carbon
      atom.
AB  - A novel type of metastable complexes of metal (such as Na) atoms with a super
      fluorinated carbon molecule is investigated, with a carbon atom exhibiting a
      unique, pentavalent character. It is induced by the charge transfer from the
      alkali metal component, followed by a geometric compression of the ion pair
      system. Analysis of the electron-density distribution confirms the real chemical
      nature of the extra C-F bond. Structure and stability of the system are
      characterized ab initio, and a spectrum of electronic perturbations is
      considered. The ways of forming the systems are discussed, and the spectroscopic
      parameters are predicted, facilitating their detection in experiments.

PMID- 17020248
TI  - Interface and molecular electronic structure vs tunneling characteristics of CH3-
      and CF3-terminated thiol monolayers on Au(111).
AB  - By means of density functional theory calculations, we investigate work
      functions, energy level alignments, charge transfers, and tunneling
      characteristics of CH3- and CF3-terminated alkane- and diphenylthiol monolayers
      on Au(111). While the alignments of the energy levels and the charge transfers at
      the metal-molecule interface are found to be determined by the value of the clean
      Au surface work function relative to the HOMO ionization potential (IP) at the
      thiolate end of the monolayer, the change of work function for the modified
      Au(111) surface is dominated by the properties of the thiolate monolayer,
      including the character, saturated or conjugated, of the molecule and the
      chemical nature and orientation of the terminal group. The tunneling currents
      through the adsorbed molecular monolayers are calculated using the Tersoff-Hamann
      approach. The computed difference between the I-V characteristics for the CH3-
      and CF3-terminated alkanethiol monolayers agree well with available experimental
      data. The energy barrier at the metal-molecule interface, the molecular
      electronic structure, and the IP of the terminal group are the key parameters
      which determine the tunneling properties.

PMID- 17020249
TI  - A possible union of chemical bonding, reactivity, and kinetics.
AB  - In this communication, we report for the first time the reactivity behavior at
      the transition state, the connection between the equireactivity configuration and
      the activation barrier, and a possible principle of reactivity conservation along
      the reaction paths of typical thermoneutral and exo (endo) thermic reactions.

PMID- 17020250
TI  - Time-dependent radiolytic yields of the solvated electrons in 1,2-ethanediol, 1,2
      propanediol, and 1,3-propanediol from picosecond to microsecond.
AB  - The absorption spectra of the solvated electron in 1,2-ethanediol (12ED), 1,2
      propanediol (12PD), and 1,3-propanediol (13PD) have been determined by nanosecond
      pulse radiolysis techniques. The maximum of the absorption band located at 570,
      565, and 575 nm for these three solvents, respectively. With 4,4'-bipyridine
      (44Bpy) as a scavenger, the molar extinction coefficients at the absorption
      maximum of the solvated electron spectrum have been evaluated to be 900, 970, and
      1000 mol-1 m2 for 12ED, 12PD, and 13PD, respectively. These values are two-thirds
      or three-fourths of the value usually reported in the literature. With these
      extinction coefficients, picosecond pulse radiolysis studies have allowed us to
      depict the radiolytic yield of the solvated electron in these solvents as a
      function of time from picosecond to microsecond. The radiolytic yield in these
      viscous solvents is found to be strongly different from that of water solution.

PMID- 17020251
TI  - Excited-state charge transfer at a conical intersection: effects of an
      environment.
AB  - The influence of a polar and polarizable environment on charge transfer processes
      at a conical intersection (CI) can be described by a diabatic free energy model
      yielding coupled surfaces as a function of both molecular coordinates and a
      solvent coordinate. We extend and apply this model for the S1-S0 CI in protonated
      Schiff bases, representing a model for retinal isomerization (Faraday Discuss.
      2004, 127, 395, 2004). A dielectric continuum description of the solvent is
      combined with a minimal, two-electron-two-orbital electronic structure model
      according to Bonacic-Koutecky, Koutecky, and Michl (Angew. Chem. 1987, 26, 170),
      which characterizes the charge translocation effects at the CI. The model
      predicts that the nonequilibrium solvent state resulting from the S0-->S1 Franck
      Condon transition can entail the disappearance of the CI, such that solvent
      motion is necessary to reach the CI seam. The concerted evolution of the
      intramolecular coordinates and the solvent coordinate is illustrated by an
      excited-state minimum energy path.

PMID- 17020252
TI  - Synthesis and photophysical investigation of new porphyrin derivatives with beta
      pyrrole ethynyl linkage and corresponding dyad with [60] fullerene.
AB  - Two new beta-substituted arylethynyl meso-tetraphenylporphyrins, 2-[(4'
      formyl)phenyl]ethynyl-5,10,15,20-tetraphenylporphyrin (system A) and 2-[(4'
      methyl)phenyl]ethynyl-5,10,15,20-tetraphenylporphyrin (system B) and their zinc
      derivatives were synthesized by palladium catalysis, using a synthetic approach
      that affords high yields of the target systems. Comparative ultraviolet-visible
      (UV-vis), NMR, and cyclic voltammetry studies of such macrocycles reveal the
      presence of an extensive conjugation between the tetrapyrrolic ring and the
      linker, through pi-pi orbital interaction. This interaction was observed in the
      form of a "push-pull" effect that moves the electronic charge between the
      porphyrin and the aldehyde group of system A. System B, bearing a methyl group
      instead of the formyl group, was synthesized in order to evaluate the effect of
      the substitution on the charge delocalization, which is necessary to corroborate
      the push-pull mechanism hypothesis. The new porphyrin, system A, was also used as
      a starting material for the synthesis of new porphyrin-fullerene dyads in which
      the [60]fullerene is directly linked to the tetrapyrrolic rings by
      ethynylenephenylene subunits. Fluorescence and transient absorption measurements
      of the new dyads reveal that ultrafast energy and electron transfer occur,
      respectively, in nonpolar and polar solvents, with high values of the rate
      constant. The UV-vis, NMR, and cyclic voltammetry results show that it is
      possible for both energy and electron transfer between porphyrin and fullerene to
      take place through the pi-bond interaction. Such results evidence that the
      coupling between the donor and acceptor moieties is strong enough for possible
      photovoltaic applications.

PMID- 17020253
TI  - Femtosecond spectroscopic studies of the one- and two-photon excited-state
      dynamics of 2,2,17,17-tetramethyloctadeca-5,9,13-trien-3,7,11,15-tetrayne: a
      trimeric oligodiacetylene.
AB  - The excited-state dynamics of an oligomer of polydiacetylene, 2,2,17,17
      tetramethyloctadeca-5,9,13-trien-3,7,11,15-tetrayne, dissolved in n-hexane have
      been studied by femtosecond fluorescence upconversion and polarized transient
      absorption experiments under one- and two-photon excitation conditions.
      Spectroscopically monitoring the population relaxation in the excited states in
      real time results in a distinct time separation of the dynamics. It has been
      concluded that the observed dynamics can be fully accounted for on the basis of
      the two lower excited states of the target molecule. The S1 (2(1)Ag) state, which
      cannot be excited from the ground state with one-photon absorption, is verified
      to be populated via internal conversion in 200+/-40 fs from the strong dipole
      allowed S2 (1(1)Bu) state. The population in the "hot" S1 state subsequently
      cools with a time constant of 6+/-1 ps and decays back to the ground state with a
      lifetime of 790+/-12 ps.

PMID- 17020254
TI  - Upconverted emission from pyrene and di-tert-butylpyrene using Ir(ppy)3 as
      triplet sensitizer.
AB  - Metal-to-ligand charge-transfer sensitized upconverted fluorescence in
      noncovalent triplet energy transfer assemblies is investigated using Ir(ppy)3 as
      the sensitizer (ppy=2-phenylpyridine) and pyrene or 3,8-di-tert-butylpyrene as
      the triplet acceptor/annihilator. Upconverted singlet fluorescence from pyrene or
      3,8-di-tert-butylpyrene resulting from triplet-triplet annihilation (TTA) is
      observed following selective excitation of Ir(ppy)3 in deaerated dichloromethane
      solutions using 450-nm laser pulses. In both systems, the TTA process is
      confirmed by the near quadratic dependence of the upconverted fluorescence
      intensity on incident light power, measured by integrating the upconverted
      delayed fluorescence kinetic traces as a function of incident excitation power.
      At the relatively high concentrations of pyrene that were utilized, pyrene
      excimer formation was detected by its characteristic broad emission centered near
      470 nm. In essence, selective excitation of Ir(ppy)3 ultimately resulted in the
      simultaneous sensitization of both singlet pyrene and pyrene excimers, and the
      latter degrades the energy stored in the pyrene singlet excited state.
      Furthermore, in the case of di-tert-butylpyrene/Ir(ppy)3, the formation of
      excimers is successfully blocked because of the presence of the sterically
      hindering tert-butyl groups. The current work demonstrates that sensitized TTA is
      indeed accessible to chromophore systems beyond those previously reported,
      suggesting the generality of the approach.

PMID- 17020255
TI  - Solvent effect on the photophysical properties of the anticancer agent
      ellipticine.
AB  - This paper investigates how solution conditions, especially solvent polarity and
      hydrogen bonding, affect the fluorescence of ellipticine, a natural plant
      alkaloid with anticancer activity. A total of 16 solvents that cover a wide range
      of polarities were tested. The ultraviolet (UV) absorption and fluorescence
      emission of ellipticine were found to be solvent dependent. The absorption and
      emission maximum shifted to higher wavelengths (red shift) with increased solvent
      polarity. The difference in absorption and emission maximum (Stokes' shift) was
      large, approximately 10,000-11,000 cm-1, in polar solvents (with orientation
      polarizability Deltaf>0.2) but unusually small, approximately 8900 cm-1, in
      nonpolar solvents (hexane and cyclohexane). Large Stokes' shifts were due to an
      intramolecular charge transfer (ICT), which was enabled by large solvent polarity
      and hydrogen bonding of ellipticine with the solvents. Two transitions were found
      in the Lippert-Mataga plot between (1) nonpolar and semipolar solvents and
      between (2) semipolar and polar solvents. The first transition reflected the
      formation of hydrogen bonds between ellipticine and the solvents whereas the
      second transition indicated that ellipticine underwent an ICT. In addition, the
      larger extinction coefficients and the longer lifetime of ellipticine obtained in
      protic solvents were attributed to the formation of stronger hydrogen bonds. The
      photophysical response of ellipticine to changes in solvent polarity and hydrogen
      bond formation could be used to infer the location of ellipticine in a
      heterogeneous medium, namely liposomes in aqueous solution. A relatively large
      red shift of emission in liposomes indicated that ellipticine may be in a more
      polar environment with respect to the lipid bilayer, possibly close to the
      hydrophilic interface.

PMID- 17020256
TI  - Theoretical investigation of luminescence behavior as a function of alkyl chain
      size in 4-aminobenzonitrile alicyclic derivatives.
AB  - There is still controversy about the structure of the intramolecular charge
      transfer (ICT) emitting species in pi-electron donor-acceptor systems that show
      dual fluorescence. Although the twisted ICT model is quite generally accepted,
      the planar ICT model is not ruled out because firm experimental evidence supports
      it. Among these it is the fact that some rigidized systems such as bicyclic 4
      aminobenzonitrile derivatives exhibit dual fluorescence. We present here an ab
      initio CASSCF/CASPT2 study of a series of these compounds with the alicyclic
      chain ranging from 5 to 7 carbon atoms and compare their ICT mechanism with the
      more flexible 4-aminobenzonitrile (ABN) and 4-(dimethylamino)benzonitrile
      (DMABN). We present the energetics, geometries, and valence bond structures of
      the critical points of the potential-energy surfaces of the ground, local excited
      (LE), and ICT states. Our results show that the photophysical differences of the
      studied systems may be rationalized by two factors: the position of the ICT and
      LE potential-energy surfaces at the first stages of the ICT reaction and the
      relative energies of the excited-state minima. Computational evidence is
      presented that a twisted ICT structure can be adopted in some molecules such as
      NXC6 and NXC7 and that the anomalous band of the fluorescence spectra of these
      systems is emitted from a twisted ICT species.

PMID- 17020257
TI  - Gas-phase NMR measurements, absolute shielding scales, and magnetic dipole
      moments of 29Si and 73Ge nuclei.
AB  - New gas-phase NMR measurements of the shielding constants of 29Si, 73Ge, and 1H
      nuclei in SiH4 and GeH4 are reported. The results, extrapolated to zero density,
      provide accurate isolated molecule values, best suited for comparison with
      theoretical calculations. Using the recent ab initio results for these molecules
      and the measured chemical shifts, we determine the absolute shielding scales for
      29Si and 73Ge. This allows us to provide new values of the nuclear magnetic
      dipole moments for these two nuclei; in addition, we examine the dipole moments
      of 13C and 119Sn.

PMID- 17020258
TI  - Vibrational spectroscopy and ab initio studies of lithium bis(oxalato)borate
      (LiBOB) in different solvents.
AB  - The effect of lithium ion coordination with the bis(oxalato)borate (BOB-)
      [B(C2O4)2]- anion in DMSO, PEG, PPG, and d-PPG has been studied in detail by IR
      and Raman spectroscopy. Ab initio calculations were performed to allow a
      consistent analysis of the experimental data. The main features observed in the
      IR and Raman spectra correspond to the presence of "free", un-coordinated, BOB-
      anions. Only with use of d-PPG as solvent a small amount of Li+...BOB- ion pairs
      were detected. The Raman spectra and the calculations together indicate that Li+
      coordinates bidentately with two end-oxygen atoms of the BOB- anion. The
      identification of ion pairs can be used to reveal limitations of LiBOB based
      electrolytes. The results for LiBOB are compared with literature on other Li
      salts.

PMID- 17020259
TI  - Time-resolved IR spectroscopy of N-methylthioacetamide: trans-->cis isomerization
      upon n-pi and pi-pi excitation and cis-->trans photoreaction.
AB  - Time-resolved infrared spectroscopy was used to study the photoisomerization of N
      Methylthioacetamide (NMTAA) in D2O in both the cis-->trans and the trans-->cis
      direction upon selective excitation of the n-pi (S1) and pi-pi (S2) electronic
      transitions. While isomerization and the return to the ground state takes place
      on two distinct time scales (<or=8 ps, approximately 250 ps) upon pi-pi
      excitation of both cis- and trans-NMTAA in D2O, ground state recovery is only
      observed on the slower time scale upon n-pi excitation. The quantum efficiency
      for trans-->cis isomerization is 30-40%, independent of the electronic state
      excited, while the cis-->trans isomerization proceeds with a 60-70% quantum
      efficiency. These results support a mechanism by which isomerization takes place
      via one common intermediate state independent of electronic excitation energy and
      initial conformation.

PMID- 17020260
TI  - UV photolysis products of propiolic acid in noble-gas solids.
AB  - Photolysis (193 nm) of propiolic acid (HCCCOOH) was studied with Fourier
      transform infrared spectroscopy in noble-gas (Ar, Kr, and Xe) solid matrixes. The
      photolysis products were assigned using ab initio quantum chemistry calculations.
      The novel higher-energy conformer of propiolic acid was efficiently formed upon
      UV irradiation, and it decayed back to the ground-state conformer on a time scale
      of approximately 10 min by tunneling of the hydrogen atom through the torsional
      energy barrier. In addition, the photolysis produced a number of matrix-isolated
      1:1 molecular complexes such as HCCH...CO2, HCCOH...CO, and H2O...C3O. The
      HCCH...CO2 complex dominated among the photolysis products, and the computations
      suggested a parallel geometry of this complex characterized by an interaction
      energy of -9.6 kJ/mol. The HCCOH...CO complex also formed efficiently, but its
      concentration was strongly limited by its light-induced decomposition. In this
      complex, the most probable geometry was found to feature the interaction of
      carbon monoxide with the OH group via the carbon atom, and the computational
      interaction energy was determined to be -18.3 kJ/mol. The formation of the strong
      H2O...C3O complex (interaction energy -21 kJ/mol) was less efficient, which might
      be due to the inefficiency of the involved radical reaction.

PMID- 17020261
TI  - Infrared spectra of the (AgCO)2 and AgnCO (n=2-4) molecules in rare-gas matrices.
AB  - Reactions of laser-ablated silver atoms with carbon monoxide molecules in solid
      argon and neon have been investigated using matrix-isolation IR spectroscopy.
      Small silver cluster carbonyls, (AgCO)2 and AgnCO (n=2-4), as well as mononuclear
      silver carbonyls, Ag(CO)2 and Ag(CO)3, are generated upon sample annealing in the
      argon experiments and are characterized on the basis of the isotopic
      substitution, the CO concentration change, and the comparison with theoretical
      predictions. However, these polynuclear carbonyls are absent from the neon
      experiments. Density functional theory calculations have been performed on these
      silver carbonyls and the corresponding ligand-free silver clusters, which support
      the identification of these silver carbonyls from the matrix IRspectrum. A
      terminal CO has been found in the most stable structures of (AgCO)2, Ag2CO,
      Ag3CO, and Ag4CO. Furthermore, a plausible reaction mechanism has been proposed
      to account for the formation of the (AgCO)2 and AgnCO (n=2-4) molecules.

PMID- 17020262
TI  - A collision theory-based derivation of semiempirical equations for modeling
      dispersive kinetics and their application to a mixed-phase crystal decomposition.
AB  - In recent works, the author has shown the utility of new, semiempirical kinetic
      model equations for treating dispersive chemical processes ranging from slow
      (minute/hour time scale) solid-state phase transformations to ultrafast
      (femtosecond) reactions in the gas phase. These two fundamental models (one for
      homogeneous/deceleratory sigmoidal conversion kinetics and the other for
      heterogeneous/acceleratory sigmoidal kinetics; isothermal conditions), based on
      the assumption of a "Maxwell-Boltzmann-like" distribution of molecular activation
      energies, provide a novel, quantum-based interpretation of the kinetics. As an
      extension to previous work, it is shown here that the derivation of these
      dispersive kinetic equations is supported by classical collision theory (i.e.,
      for gas-phase applications). Furthermore, the successful application of the
      approach to the kinetic modeling of the solid-state decomposition of a binary
      system, CO2.C2H2, is demonstrated. Finally, the models derived appear to explain
      some of the (solid-state) kinetic data collected using isoconversional techniques
      such as those often reported in the thermal analysis literature.

PMID- 17020263
TI  - Proton affinity of canavanine and canaline, oxyanalogues of arginine and
      ornithine, from the extended kinetic method.
AB  - The absolute proton affinities of the nonprotein amino acids canavanine and
      canaline have been determined using the extended kinetic method in an
      electrospray ionization quadrupole ion trap instrument. Canavanine results from
      the substitution of an oxygen atom for the delta-CH2 group in the side chain of
      the protein amino acid arginine, whereas canaline results from a similar
      substitution at the delta-CH2 group in the side chain of ornithine. Absolute
      proton affinities of 1001+/-9 and 950+/-7 kJ/mol are obtained for canavanine and
      canaline, respectively. For canaline, this proton affinity is in excellent
      agreement with theoretical predictions obtained using the hybrid density
      functional theory method B3LYP/6-311++G**//B3LYP/6-31+G*. For canavanine, theory
      predicts a somewhat larger proton affinity of 1015 kJ/mol. Oxygen atom
      substitution in these nonprotein amino acids results in a decrease in their
      proton affinities of 40-50 kJ/mol compared to arginine and ornithine.

PMID- 17020264
TI  - Experimental and theoretical studies of the kinetics of the reactions of OH
      radicals with acetic acid, acetic acid-d3 and acetic acid-d4 at low pressure.
AB  - The kinetics of the reactions of OH with acetic acid, acetic acid-d3 and acetic
      acid-d4 were studied from 2 to 5 Torr and 263-373 K using a discharge flow system
      with resonance fluorescence detection of the OH radical. The measured rate
      constants at 300 K for the reaction of OH with acetic acid and acetic acid-d4
      (CD3C(O)OD) were (7.42+/-0.12)x10(-13) and (1.09+/-0.18)x10(-13) cm3 molecule-1 s
      1 respectively, and the rate constant for the reaction of OH with acetic acid-d3
      (CD3C(O)OH) was (7.79+/-0.16)x10(-13) cm3 molecule-1 s-1. These results suggest
      that the primary mechanism for this reaction involves abstraction of the acidic
      hydrogen. Theoretical calculations of the kinetic isotope effect as a function of
      temperature are in good agreement with the experimental measurements using a
      mechanism involving the abstraction of the acidic hydrogen through a hydrogen
      bonded complex. The rate constants for the OH+acetic acid and OH+acetic acid-d4
      reactions display a negative temperature dependence described by the Arrhenius
      equations kH(T)=(2.52+/-1.22)x10(-14) exp((1010+/-150)/T) and kD(T)=(4.62+/
      1.33)x10(-16) exp((1640+/-160)/T) cm3 molecule-1 s-1 for acetic acid and acetic
      acid-d4, respectively, consistent with recent measurements that suggest that the
      lifetime of acetic acid at the low temperatures of the upper troposphere is
      shorter than previously believed.

PMID- 17020265
TI  - Reaction of hydroxyl radicals with azacytosines: a pulse radiolysis and
      theoretical study.
AB  - Pulse radiolysis and density functional theory (DFT) calculations at B3LYP/6
      31+G(d,p) level have been carried out to probe the reaction of the water-derived
      hydroxyl radicals (*OH) with 5-azacytosine (5Ac) and 5-azacytidine (5Acyd) at
      near neutral and basic pH. A low percentage of nitrogen-centered oxidizing
      radicals, and a high percentage of non-oxidizing carbon-centered radicals were
      identified based on the reaction of transient intermediates with 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonate), ABTS2-. Theoretical calculations suggests that
      the N3 atom in 5Ac is the most reactive center as it is the main contributor of
      HOMO, whereas C5 atom is the prime donor for the HOMO of cytosine (Cyt) where the
      major addition site is C5. The order of stability of the adduct species were
      found to be C6-OH_5Ac*>C4-OH_5Ac*>N3-OH_5Ac*>N5-OH_5Ac* both in the gaseous and
      solution phase (using the PCM model) respectively due to the additions of *OH at
      C6, C4, N3, and N5 atoms. These additions occur in direct manner, without the
      intervention of any precursor complex formation. The possibility of a 1,2
      hydrogen shift from the C6 to N5 in the nitrogen-centered C6-OH_5Ac* radical is
      considered in order to account for the experimental observation of the high yield
      of non-oxidizing radicals, and found that such a conversion requires activation
      energy of about 32 kcal/mol, and hence this possibility is ruled out. The
      hydrogen abstraction reactions were assumed to occur from precursor complexes
      (hydrogen bonded complexes represented as S1, S2, S3, and S4) resulted from the
      electrostatic interactions of the lone pairs on the N3, N5, and O8 atoms with the
      incoming *OH radical. It was found that the conversion of these precursor
      complexes to their respective transition states has ample barrier heights, and it
      persists even when the effect of solvent is considered. It was also found that
      the formation of precursor complexes itself is highly endergonic in solution
      phase. Hence, the abstraction reactions will not occur in the present case.
      Finally, the time dependent density functional theory (TDDFT) calculations
      predicted an absorption maximum of 292 nm for the N3-OH_5Ac* adduct, which is
      close to the experimentally observed spectral maxima at 290 nm. Hence, it is
      assumed that the addition to the most reactive center N3, which results the N3
      OH_5Ac* radical, occurs via a kinetically driven process.

PMID- 17020267
TI  - Density functional study of small neutral and charged silver cluster hydrides.
AB  - Small neutral, anionic, and cationic silver cluster hydrides AgnH and anionic
      HAgnH (n=1-7) have been studied using the PW91PW91 density functional method. It
      was found that the most stable structure of the AgnH complex (neutral or charged)
      does not always come from that of the lowest energy bare silver cluster plus an
      attached H atom. Among various possible adsorption sites, the bridge site is
      energetically preferred for the cationic and most cases of neutral Agn. For
      anionic Agn, the top site is preferred for smaller Agn within n<or=4 while the
      bridge site is preferred for bigger clusters. After binding of the second H atom,
      the obtained lowest energy structures HAgnH- are those with two H atoms shared
      with only one Ag atom in anionic clusters. Natural bond orbital analysis shows
      that, irrespective of the charge state, electrons always transfer from silver
      atoms to adsorbate. Significant odd-even alternation patterns that hydrogen atoms
      bind more strongly with odd-electron bare clusters than with even-electron bare
      clusters can be observed.

PMID- 17020266
TI  - First-principle computational study on the full conformational space of L
      threonine diamide, the energetic stability of cis and trans isomers.
AB  - First-principle computations were carried out on the conformational space of
      trans and cis peptide bond isomers of HCO-Thr-NH2. Using the concept of
      multidimensional conformational analysis (MDCA), geometry optimizations were
      performed at the B3LYP/6-31G(d) level of theory, and single-point energies as
      well as thermodynamic functions were calculated at the G3MP2B3 level of theory
      for the corresponding optimized structures. Two backbone Ramachandran-type
      potential energy surfaces (PESs) were computed, one each for the cis and trans
      isomers, keeping the side chain at the fully extended orientation
      (chi1=chi2=anti). Similarly, two side chain PESs for the cis and trans isomers
      were generated for the (phi=psi=anti) orientation corresponding to approximately
      the betaL backbone conformation. Besides correlating the relative Gibbs free
      energy of the various stable conformations with the number of stabilizing
      hydrogen bonds, the process of trans-->cis isomerization is discussed in terms of
      intrinsic stabilities as measured by the computed thermodynamic functions.

PMID- 17020268
TI  - Characterizing potential surface topographies through the distribution of saddles
      and minima.
AB  - Three related clusters of thirteen particles bound by pairwise Morse potentials
      with different ranges are the vehicles for relating the dynamics and kinetics of
      these clusters to the topographies of their energy landscapes. The analyses are
      based on the distributions of minima and saddles, on the asymmetries of the
      barriers and the kinetics of passage among the energy bands that the
      distributions of minima display. While all three of the examples are essentially
      structure-seekers, the extent of this character is clearly related to the range
      of the potential.

PMID- 17020269
TI  - Charge transfer in polypeptides: effect of secondary structures on charge
      transfer integral and site energies.
AB  - We have theoretically studied the charge transfer in glycine polypeptide using
      quantum mechanical models based on a tight-binding Hamiltonian approach. The
      charge-transfer integrals and site energies involved in the transport of positive
      charge through the peptide bond in glycine polypeptide have been calculated. The
      charge-transfer integrals and site energies have been calculated directly from
      the matrix elements of the Kohn-Sham Hamiltonian defined in terms of the
      molecular orbitals of the individual fragments of the glycine polypeptide. In
      addition to this, we have calculated the rate of charge transfer between a
      neighboring amino acid subgroup through the Marcus rate equation. These
      calculations have been performed for the different secondary structures of the
      glycine model peptide such as linear, alpha-helix, 3(10)-helix, and antiparallel
      beta-sheet by varying the dihedral angles omega, varphi, and psi along the Calpha
      carbon of amino acid subgroup. Present theoretical results confirm that the
      charge transfer through the peptide bond is strongly affected by the
      conformations of the oligopeptide.

PMID- 17020270
TI  - Theoretical characterization of end-on and side-on peroxide coordination in
      ligated Cu2O2 models.
AB  - The relative energetics of mu-eta1:eta1 (trans end-on) and mu-eta2:eta2 (side-on)
      peroxo isomers of Cu2O2 fragments supported by 0, 2, 4, and 6 ammonia ligands
      have been computed with various density functional, coupled-cluster, and
      multiconfigurational protocols. There is substantial disagreement between the
      different levels for most cases, although completely renormalized coupled-cluster
      methods appear to offer the most reliable predictions. The significant biradical
      character of the end-on peroxo isomer proves problematic for the density
      functionals, while the demands on active space size and the need to account for
      interactions between different states in second-order perturbation theory prove
      challenging for the multireference treatments. In the latter case, it proved
      impossible to achieve any convincing convergence.

PMID- 17020271
TI  - Analysis of electron delocalization in aromatic systems: individual molecular
      orbital contributions to para-delocalization indexes (PDI).
AB  - Our research group has recently defined two new aromaticity indexes based on the
      analysis of electron delocalization in aromatic species using the quantum theory
      of atoms-in-molecules. One of these indexes is the para-delocalization index
      (PDI) that measures the electronic delocalization between para-related carbon
      atoms in six-membered rings. In this paper, we show that this index can be
      partitioned into individual molecular orbital contributions. We have applied this
      PDI decomposition to several polycyclic aromatic hydrocarbons showing that this
      partitioning provides new insight into the origin of aromaticity.

PMID- 17020272
TI  - The sign and magnitude of 2hJ(F,F) and 1hJ(F,H) in FH...FH. A CLOPPA analysis of
      their distance dependence.
AB  - The sign change of the intermolecular (2h)J(F,F) coupling in the (HF)2 dimer as a
      function of the F-F distance is discussed by means of the CLOPPA method. It is
      found that it is due to the competition of positive and negative contributions
      involving the interaction of the sigma lone pair of the acceptor nucleus with
      vacant molecular orbitals localized in the F-H...F moiety and with other
      molecular orbitals localized in the donor molecule. The origin of the sign of
      each contribution is fully determined by analyzing the response of the electronic
      system to the magnetic perturbation at the acceptor F nucleus. (2h)J(F,F)
      coupling in the FH...F-, which is positive for all F-F distances, is also
      analyzed in order to look for the differences with the former case.

PMID- 17020273
TI  - Hartree-Fock-Heitler-London method. 2. First and second row diatomic hydrides.
AB  - The Hartree-Fock-Heitler-London, HF-HL, method is a new ab initio approach which
      variationally combines the Hartree-Fock, HF, and the Heitler-London, HL,
      approximations, yielding correct dissociation products. Furthermore, the new
      method accounts for nondynamical correlation and explicitly considers avoided
      crossing. With the HF-HL model we compute the ground-state potential energy
      curves for H2 [1Sigma+g], LiH [X 1Sigma+], BeH [2Sigma+], BH [1Sigma+], CH [2Pi],
      NH [3Sigma-], OH [2Pi], and FH [1Sigma+], obtaining in average 80% of the
      experimental binding energy with a correct representation of bond breaking.
      Inclusion of ionic configurations improves the computed binding energy. The
      computed dipole moment is in agreement with laboratory data. The dynamical and
      nondynamical correlation energies for atomic and molecular systems with 2-10
      electrons are analyzed. For BeH the avoided crossing of the two lowest [2Sigma+]
      states is considered in detail. The HF-HL function is proposed as the zero-order
      reference wave function for molecular systems. To account for the dynamical
      correlation energy a post-HF-HL technique based on multiconfiguration expansions
      is presented. We have computed the potential energy curves for H2 [1Sigma+g], HeH
      [2Sigma+], LiH [X1Sigma+], LiH [A1Sigma+], and BeH [2Sigma+]. The corresponding
      computed binding energies are 109.26 (109.48), 0.01 (0.01), 57.68 (58.00), 24.19
      (24.82), and 49.61 (49.83) kcal/mol, with the experimental values given in
      parentheses. The corresponding total energies are -1.1741, -3.4035, -8.0695, 
      7.9446, and -15.2452 hartrees, respectively, the best ab initio variational
      published calculations, H2 excluded.

PMID- 17020274
TI  - Radical trifluoromethylation of ketone silyl enol ethers by activation with
      dialkylzinc.
AB  - [reaction: see text] The radical trifluoromethylation of ketone silyl enol ethers
      gave alpha-CF(3) ketones in good yields with wide scope of the ketonic substrates
      including acyclic ketones and cyclopentanone. The use of dialkylzinc to activate
      the silyl enol ethers is the key to the efficient radical trifluoromethylation.

PMID- 17020275
TI  - Stylissadines A and B: the first tetrameric pyrrole-imidazole alkaloids.
AB  - [reaction: see text] Pyrrole-imidazole alkaloids are widely distributed in marine
      sponges of the orders Halichondrida and Agelasida. Chemical investigation of the
      Caribbean sponge Stylissa caribica led to the isolation of the first tetrameric
      pyrrole-imidazole alkaloids. The so-called stylissadines are the largest and most
      complex pyrrole-imidazole alkaloids discovered so far and are therefore a major
      challenge for the structure determination by NMR spectroscopy. Their isolation
      and structure elucidation are discussed in detail.

PMID- 17020276
TI  - Macrocyclic chiral receptors toward enantioselective recognition of naproxen.
AB  - [structure: see text] A macrocyclic receptor based on a bischromenylurea and an
      alpha,alpha'-(o,o'-dialkyl)diphenyl-p-xylylenediamine spacer provides a C(2)
      chiral cavity to associate carboxylates by H-bonds. The extent of the selectivity
      obtained for the racemic receptor 2 and enantiomerically pure (S)-naproxen is
      7.2:1. Steric repulsions close to the cavity are decisive for the chiral
      selectivity.

PMID- 17020277
TI  - Organocatalytic living ring-opening polymerization of cyclic carbosiloxanes.
AB  - [reaction: see text] An organocatalytic route to narrowly dispersed
      poly(carbosiloxanes) of predictable molecular weight and end group fidelity is
      described. N-Heterocyclic carbenes (NHC) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene
      (TBD) catalyze the ring opening of cyclic carbosiloxanes. The pK(b) of the
      catalyst is important in preventing adverse transetherification reactions and
      obtaining well-defined polymers. Mechanistic studies indicate that hydrogen
      bonding to TBD or the NHC activates alcohols or silanols for ring-opening
      reactions.

PMID- 17020278
TI  - New zinc(II)-based catalyst for asymmetric azomethine ylide cycloaddition
      reactions.
AB  - [reaction: see text] A new chiral aziridino alcohol ligand for zinc(II)-catalyzed
      azomethine ylide cycloadditions is described. In the presence of this catalyst, N
      arylidene glycine methyl esters react with a variety of dipolarophiles to give
      substituted pyrrolidines in very good to excellent chemical yields and up to 95%
      ee. The absolute sense of asymmetric induction appears to be dipolarophile
      dependent.

PMID- 17020279
TI  - Phenylalanine 445 within oxidosqualene-lanosterol cyclase from Saccharomyces
      cerevisiae influences C-Ring cyclization and deprotonation reactions.
AB  - [reaction: see text] We describe the Saccharomyces cerevisiae oxidosqualene
      lanosterol cyclase Phe445 site-saturated mutants that generate truncated
      tricyclic and altered deprotonation product profiles. Among these mutants, only
      polar side-chain group substitutions genetically complemented yeast viability and
      produced spatially related product diversity, supporting the Johnson model that
      cation-pi interactions between a carbocationic intermediate and an enzyme can be
      replaced by an electrostatic or polar side chain to stabilize the cationic
      intermediate, but with product differentiation.

PMID- 17020281
TI  - Donor-acceptor-donor-type liquid crystal with a pyridazine core.
AB  - [structure: see text] A new liquid crystalline material having an
      ethylenedioxythiophene-pyridazine-ethylenedioxythiophene (EDOT-PDZ-EDOT) core
      with two peripheral long alkyl chains was prepared. The designated donor-acceptor
      donor (D-A-D)-type core structure induced a distinct smectic liquid crystalline
      phase due to the strong intermolecular interaction. The photophysical property
      and the layer structure of the liquid crystal were investigated by differential
      scanning calorimetry, polarized light microscopy, X-ray diffraction, and cyclic
      voltammetry.

PMID- 17020280
TI  - Energetics of an n --> pi interaction that impacts protein structure.
AB  - [structure: see text] The trans/cis ratio of the amide bond in N-formylproline
      phenylesters correlates with electron withdrawal by a para substituent. The slope
      of the Hammett plot (rho = 0.26) is indicative of a substantial effect. This
      effect arises from a favorable n --> pi interaction between the amide oxygen and
      ester carbonyl. In a polypeptide chain, an analogous interaction can stabilize
      the conformation of trans peptide bonds, alpha-helices, and polyproline type-II
      helices.

PMID- 17020282
TI  - Synthesis of a new cross-linkable perfluorocyclobutane-based hole-transport
      material.
AB  - [reaction: see text] A new curable arylamine containing a perfluorocyclobutane
      (PFCB) structure without an acidic group was synthesized. The material was
      thermally cured on ITO after spin-coating. The polymer showed excellent solvent
      resistance, high thermal stability, high transparency, and good surface
      smoothness.

PMID- 17020283
TI  - Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation
      inhibitors as potential antitubercular agents.
AB  - [reaction: see text] The antitubercular nucleoside antibiotics 1 and 2 were
      recently described that inhibit the adenylate-forming enzyme MbtA and disrupt
      biosynthesis of the virulence-conferring siderophore known as mycobactin in
      Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor
      scaffold by replacing the labile acylsulfamate linkage (highlighted) with the
      more chemically robust beta-ketosulfonamide linkage of 3 and 4.

PMID- 17020284
TI  - Stereochemical control in the reduction of 2-chromanols.
AB  - [reaction: see text] Reduction of C5-substituted 2-hydroxychromans selectively
      provides 2,4-cis-chromans using large silane reductants and 2,4-trans-chromans
      using the smaller silane PhSiH(3). The stereochemical outcome has been
      rationalized on the basis of a Curtin-Hammett kinetic situation arising from
      hydride delivery to two different conformations of an intermediate oxocarbenium
      ion. This method provides a powerful way to control the relative stereochemistry
      of these substructures which are prevalent in bioactive natural products.

PMID- 17020285
TI  - Detection of Hg2+ in aqueous solutions with a foldamer-based fluorescent sensor
      modulated by surfactant micelles.
AB  - [structure: see text] A hybrid foldamer constructed from six cholate units and
      two methionines was labeled with a DANSYL (DNS) group. The foldamer was
      solubilized by surfactant micelles to allow its usage as a fluorescent sensor for
      mercury ions present in the micromolar range in aqueous solutions. Its
      sensitivity was largely independent of the concentration of nonionic surfactants
      but was strongly influenced by both the nature and the concentration of ionic
      surfactants.

PMID- 17020286
TI  - Identification and stereochemical assignment of the beta-hydroxytryptophan
      intermediate in the echinomycin biosynthetic pathway.
AB  - [reaction: see text] Little is known about how quinoxaline-2-carboxylic acid (QC)
      is synthesized in nature. On the basis of analysis of echinomycin biosynthetic
      gene clusters as well as feeding experiments with labeled precursors, we have
      proposed a biosynthetic pathway to QC and identified the (2S,3S)-beta
      hydroxytryptophan as a key intermediate.

PMID- 17020287
TI  - Sequential metal ion assembly in cyclic phenylazomethine.
AB  - [reaction: see text] Cyclic phenylazomethines with methylene spacers (CPA-M) are
      obtained by dehydration of diamine with diketone. During the titration of CPA-M
      4mer with FeCl(3), we observe two consecutive isosbestic points in the UV-vis
      spectra. We conclude that complexation occurs in two consecutive steps. Our
      analysis suggests that the stepwise metal ion assembly is caused by a difference
      in the basicity of the imine conformers. Metal ion binding first occurs at the Z
      imines followed by coordination to the E imine. Finally, metal ion assembly in
      this compound can be controlled electrochemically.

PMID- 17020288
TI  - Maoecrystal Z, a cytotoxic diterpene from Isodon eriocalyx with a unique
      skeleton.
AB  - [structure: see text] A novel diterpene with an unprecedented tetracyclic
      6,7:8,15-di-seco-7,20-olide-6,8-cyclo-ent-kaurane skeleton, named maoecrystal Z
      (1), has been isolated from the leaves of a Chinese medicinal herb, Isodon
      eriocalyx (Labiatae). Its structure was determined by comprehensive NMR and MS
      spectroscopic analysis coupled with single-crystal X-ray crystallographic
      diffraction. Compound 1 exhibited comparable inhibitory effect against human K562
      leukemia, MCF7 breast, and A2780 ovarian tumor cells with IC(50) = 2.90, 1.63,
      and 1.45 microg/mL and with camptothecin and paclitaxel as the positive controls.

PMID- 17020290
TI  - Macrocyclic scaffold for the collagen triple helix.
AB  - [structure: see text] Three strands of natural collagen are linked by covalent
      bonds prior to their folding into a triple helix. We report on a synthetic
      collagen in which the strands are pendent on a rigid macrocyclic scaffold of C(3)
      symmetry. The scaffold confers substantial conformational stability upon the
      collagen triple helix and makes its folding independent of concentration, both
      desirable attributes for exploring and exploiting synthetic collagens.

PMID- 17020291
TI  - Asymmetric [2 + 2] cycloaddition: total synthesis of (-)-swainsonine and (+)-6
      epicastanospermine.
AB  - [reaction: see text] An asymmetric total synthesis of (-)-swainsonine and (+)-6
      epicastanospermine is described from a common intermediate, which is obtained
      through diastereoselective [2 + 2] cycloaddition of dichloroketene to a chiral
      enol ether.

PMID- 17020289
TI  - Trisubstituted (E)-alkene dipeptide isosteres as beta-turn promoters in the
      gramicidin S cyclodecapeptide scaffold.
AB  - [reaction: see text] A concise synthesis of a gramicidin S analogue with
      trisubstituted (E)-alkene dipeptide isostere (TEADI) replacements at both d-Phe
      Pro positions was realized. Conformational analysis demonstrated that TEADIs can
      serve as type II beta-turn promoters in a cyclic scaffold and successfully mimic
      a proline residue.

PMID- 17020292
TI  - Axially chiral directly beta,beta-linked bisporphyrins: synthesis and
      stereostructure.
AB  - [reaction: see text] A novel type of "superbiaryl", the first porphyrin dimers
      with an intrinsically chiral structure, has been prepared. The atropo-enantiomers
      were configurationally assigned by HPLC-CD combined with quantum chemical CD
      calculations.

PMID- 17020293
TI  - From bifunctional nucleophilic behavior of DBU to a new heterocyclic fluorescent
      platform.
AB  - [structure: see text] An unexpected discovery of a novel cyclocondensation
      reaction of 1,8-diazabicyclo[5.4.0]undec-8-ene (DBU) with activated 1,2-dichloro
      compounds is described. The 2-aminopyrrole skeleton is generated through the
      concomitant formation of new nitrogen-carbon and carbon-carbon bonds. A new
      pentacyclic derivative formed upon the reaction of 2,3-dichloroquinoxaline with
      DBU exhibits strong fluorescence both in solutions (Phi in hexane = 0.4) and in
      the solid state.

PMID- 17020295
TI  - Desymmetrization of cyclohexa-2,5-dienes through a diastereoselective protonation
      hydroamination cascade.
AB  - [reaction: see text] Intramolecular hydroamination of cyclohexa-2,5-dienes led
      with high selectivity to the corresponding bicyclic allylic amines. This study
      demonstrates that the reaction does not proceed through a direct hydroamination
      of one of the diastereotopic olefins but more likely involves a
      diastereoselective protonation of a pentadienyl anion, followed by addition of a
      lithium amide across the double bond of the resulting 1,3-diene, and is concluded
      by a highly regioselective protonation of the final allylic anion.

PMID- 17020294
TI  - Stereochemical determination of Archazolid A and B, highly potent vacuolar-type
      ATPase inhibitors from the Myxobacterium Archangium gephyra.
AB  - [structure: see text] The relative and absolute stereochemistry of the
      structurally unique 24-membered myxobacterial macrolides archazolid A and B,
      highly potent vacuolar-type ATPase (V-ATPase) inhibitors in vitro and in vivo,
      was determined on the basis of a combination of extensive high-field NMR studies,
      including J-based configuration analysis, molecular modeling, and chemical
      methods.

PMID- 17020296
TI  - Ruthenium-catalyzed tandem olefin metathesis-oxidations.
AB  - [reaction: see text] The utility of Grubbs' 2nd generation metathesis catalyst
      has been expanded by the development of two tandem olefin metathesis/oxidation
      protocols. These ruthenium-catalyzed processes provide cis-diols or alpha-hydroxy
      ketones from simple olefinic starting materials.

PMID- 17020297
TI  - Efficient approach to the Azaspirane core of FR 901483.
AB  - [reaction: see text] An efficient approach to the azaspirane core of FR 901483 is
      described employing lithiated methoxyallene as a crucial C3 building block and a
      suitably protected enantiopure ketimine as the second component. The resulting
      dihydropyrrole derivative was smoothly converted into a spiro keto aldehyde which
      under acidic conditions provided a novel azanorbornane derivative 15. Under basic
      reaction conditions, the desired 5-azatricyclo[6.3.1.0(1,5)]dodecane skeleton 16
      was generated. The ratio of diastereomers strongly depends on the reaction
      conditions employed with l-proline in DMSO providing the highest selectivity in
      favor of one azaspirane product.

PMID- 17020298
TI  - Direct electrophilic alpha-fluorination of imines: efficient synthesis of mono-
      and difluoroimines.
AB  - [reaction: see text] A mild and efficient procedure to synthesize alpha-fluoro-
      and alpha,alpha-difluoroimines was developed. Various N-alkylimines derived from
      acetophenones were successfully monofluorinated using NFSI (N
      fluorobenzenesulfonimide) in a mixture of CH(3)CN and DMF at 0 degrees C.
      Alternatively, the same procedure without DMF gave rise to difluorinated imines
      when performed at room temperature. The obtained alpha- and alpha,alpha
      difluorinated imines were subsequently reduced to give the corresponding beta
      fluoro- and beta,beta-difluoroamines in good yield.

PMID- 17020299
TI  - Total synthesis of topopyrones B and D.
AB  - [reaction: see text] We describe a straightforward synthesis of topopyrones B and
      D, which are potent and selective inhibitors of topoisomerase I. The chemistry
      should be suitable for additional structure-activity relationship (SAR) work.

PMID- 17020300
TI  - A strategy for the total synthesis of dragmacidin E. Construction of the core
      ring system.
AB  - [reaction: see text] The construction of the dragmacidin core ring system by a
      route that features the application of a new indole annelation reaction sequence
      is described.

PMID- 17020301
TI  - A rapid divergent synthesis of highly substituted delta-lactones.
AB  - [reaction: see text] Nucleophilic 1,2-addition of (Z)-gamma-silyloxyvinylzinc
      reagents to ethyl glyoxylate followed by desilylation and cyclization affords 3,6
      dihydro-3-hydroxypyran-2-ones in good chemical yields. In situ formation of
      allylic phosphates followed by reaction with RCu(CN)Li reagents affords
      substituted 5,6-dihydropyran-2-ones. The parent compound, 3,6-dihydro-3
      hydroxypyran-2-one, undergoes allylic phosphate formation, cuprate-mediated
      allylic substitution, and 1,4-conjugate addition to afford trans-4,5
      disubstituted tetrahydropyran-2-ones in a one-pot process.

PMID- 17020302
TI  - Synthesis of 3-(aryl)alkenyl-beta-lactams by an efficient application of olefin
      cross-metathesis on solid support.
AB  - [reaction: see text] An efficient cross-metathesis on solid support for the
      synthesis of beta-lactam analogues of cholesterol absorption inhibitors is
      described. The applied strategy allows the introduction of diversity in positions
      3 and 4 of the beta-lactam ring with excellent 3,4-trans selectivity and complete
      E selectivity at the C-3 side chain.

PMID- 17020303
TI  - Optimization of the catalytic asymmetric addition of nitroalkanes to cyclic
      enones with trans-4,5-methano-L-proline.
AB  - [reaction: see text] The conjugate addition of symmetrical 2-nitroalkanes to 2
      cycloalkenones catalyzed by trans-4,5-methano-l-proline proceeds with >99% ee and
      excellent chemical yields. 1-Nitroalkanes afford diastereomeric syn/anti products
      that can be separated with good individual enantioselectivities. Proline
      hydroxamic acid and its trans-4,5-methano -l-proline hydroxamic acid are also
      effective organocatalysts in the addition of 2-nitropropane to 2-cyclohexenone
      (75% and 81% ee, respectively).

PMID- 17020304
TI  - Electrophilic allylations and benzylations of indoles in neutral aqueous or
      alcoholic solutions.
AB  - [reaction: see text] Indoles are allylated and benzylated in moderate to
      quantitative yield when stirred with allyl and benzyl halides in 80% aqueous
      acetone in the presence of NH(4)HCO(3) at room temperature.

PMID- 17020305
TI  - Synthesis of stable 2H-pyran-5-carboxylates via a catalyzed propargyl-Claisen
      rearrangement/oxa-6pi electrocyclization strategy.
AB  - [reaction: see text] The application of easily accessed propargyl vinyl ethers
      for the synthesis of monocyclic 2H-pyrans was achieved. Under the reaction
      conditions, highly substituted heterocycles were obtained in moderate to
      excellent yields. The one-pot sequence proceeds via a Ag(I)-catalyzed propargyl
      Claisen rearrangement, followed by a base-catalyzed isomerization, and 6pi
      oxaelectrocyclization, leading to the formation of stable 2H-pyrans.

PMID- 17020306
TI  - Rhodium-catalyzed multicomponent-coupling reactions involving a carborhodation
      cross-coupling sequence.
AB  - [reaction: see text] A rhodium-catalyzed multicomponent-coupling reaction has
      been developed that involves a cross-coupling with organohalides as part of the
      reaction sequence. Through several experiments toward mechanistic investigations,
      it has also been demonstrated that the reaction most likely proceeds via a
      carborhodation-oxidative addition-reductive elimination pathway, which clearly
      contrasts to the corresponding palladium-catalyzed processes.

PMID- 17020307
TI  - Stereoselective synthesis of novel 4,5-epoxy-1,2-oxazin-6-ones and alpha,beta
      epoxy-gamma-amino acids from beta-lithiated oxazolinyloxiranes and nitrones.
AB  - [reaction: see text] A stereoselective synthesis of 9,10-epoxy-1,6-dioxa-4,7
      diazaspiro[4,5]decanes has been developed on the basis of the addition of beta
      lithiated oxazolinyloxiranes to nitrones. Conversion of these spirocyclic
      derivatives into 4,5-epoxy-1,2-oxazin-6-ones and successively into alpha,beta
      epoxy-gamma-amino acids, alpha-hydroxy-gamma-amino acids, and gamma-butyrolactams
      is described.

PMID- 17020308
TI  - Fragmentation of 2,2,2-triphenylethoxychlorocarbene: evidence for ultrafast
      fragmentation-rearrangement in excited diazirines.
AB  - [reaction: see text] Photolysis of 3-(2,2,2-triphenylethoxy)-3-chlorodiazirine
      gives 2,2,2-triphenylethoxychlorocarbene which fragments with 1,2-phenyl
      migration and loss of CO and Cl(-) to yield the 1,1,2-triphenylethyl cation and
      thence 1,1,2-triphenylethene by proton loss. However, ps and fs laser flash
      photolysis provides evidence that up to 25% of the alkene product stems from
      carbocation that arises directly from excited diazirine rather than from the
      carbene.

PMID- 17020309
TI  - Novel alternative for the N-S bond formation and its application to the synthesis
      of benzisothiazol-3-ones.
AB  - [reaction: see text] The synthesis of a series of benzisothiazolone derivatives
      starting from the readily available methyl thiosalicylate is presented. The key
      cyclization step features the formation of a N-acylnitrenium ion, generated by
      the hypervalent iodine reagent PIFA, and its succeeding intramolecular trapping
      by the thiole moiety leading to the construction of the title compounds by
      formation of a new N-S bond.

PMID- 17020310
TI  - Application of the B-alkyl suzuki-miyaura cross-coupling reaction to the
      stereoselective synthesis of analogues of (3S)-oxidosqualene.
AB  - [reaction: see text] A general method is described for the direct and
      stereoselective synthesis of epoxypolyenes via Suzuki-Miyaura cross-coupling
      reaction of 1-iodoalkenes with B-alkylboron compounds. It allows for the
      straightforward and convergent assembly of compounds that are structurally
      similar to (3S)-oxidosqualene, an important intermediate in steroid biosynthesis.

PMID- 17020311
TI  - Synthetic studies on the MARDi cascade: stereoselective synthesis of heterocyclic
      seven-membered rings.
AB  - [reaction: see text] A versatile stereoselective synthesis of substituted and
      functionalized heterocyclic seven-membered rings is described. The approach
      involves a formal two-carbon ring expansion of heterocyclic cyclopentanones
      through a base-induced anionic domino three-component transformation named the
      MARDi cascade leading either to oxa-, aza-, or thiacycloheptanes bearing up to
      five contiguous stereogenic centers.

PMID- 17020312
TI  - Unexpected multifunctional effects of methylated cyclodextrins in a palladium
      charcoal-catalyzed Suzuki-Miyaura reaction.
AB  - [reaction: see text] Native and modified cyclodextrins (CDs) have shown
      polyvalent properties in a biphasic Pd/C-catalyzed Suzuki-Miyaura reaction. In
      addition to their mass transfer ability, the CDs favored the dispersion of the
      catalyst in water. With the randomly methylated CDs (RaMe-beta-CD), the gains of
      initial activities were multiplied by factors between 3.8 and 343 depending on
      the nature of the substrates. The reusability of the system was also
      demonstrated.

PMID- 17020313
TI  - Synthesis of polycyclic heterocycles via a one-pot ortho alkylation/direct
      heteroarylation sequence.
AB  - [reaction: see text] Polycyclic thiophenes and furans were synthesized using a
      one-pot ortho alkylation/direct heteroarylation reaction sequence. Under the
      optimized reaction conditions, aryl iodides were coupled with 3
      (bromoalkyl)thiophenes or -furans, affording six- and seven-membered annulated
      ring products via formation of two C-C bonds from two aryl C-H bonds.

PMID- 17020314
TI  - Regioselective entry to bromo-gamma-hydroxybutenolides: useful building blocks
      for assemblying natural product-like libraries.
AB  - [reaction: see text] We report a regioselective entry to 3-bromo- and 4-bromo-5
      hydroxy-5H-furan-2-ones by photooxidation of 3-bromofuran with a singlet oxygen
      in the presence of a suitable base. By this procedure, a variety of 3-substituted
      gamma-hydroxybutenolides have become for the first time easily accessible.
      Strategies employing these highly functionalized building blocks for the
      preparation of focused libraries of natural-like molecules are also discussed.

PMID- 17020315
TI  - Cyclobis(paraquat-p-phenylene)-based [2]catenanes prepared by kinetically
      controlled reactions involving alkynes.
AB  - [reaction: see text] Charged donor-acceptor [2]catenanes, in which the pi
      accepting cyclobis(paraquat-p-phenylene) acts as a tetracationic template for the
      threading-followed-by-clipping of acyclic oligoethers, incorporating centrally a
      pi-donating 1,5-dioxynaphthalene ring system and terminated either by acetylene
      units or by acetylene and azide functions, are the products of copper-mediated
      Eglinton coupling and Huisgen 1,3-dipolar cycloaddition, respectively.

PMID- 17020316
TI  - TiCl4/t-BuNH2-promoted hydroamination/annulation of delta-keto-acetylenes:
      synthesis of novel pyrrolo[1,2-a]indol-2-carbaldehydes.
AB  - [reaction: see text] An original TiCl(4)/t-BuNH(2)-mediated
      hydroamination/annulation domino reaction of delta-keto-acetylenes is described.
      The synthesis of pyrrolo[1,2-a]indole-2-carbaldehydes, starting from 2-carbonyl-1
      propargyl-1H-indoles runs under mild reaction conditions. A conceivable mechanism
      is also discussed. TiCl(4) has proved to be an effective multiactivity reagent:
      catalyst/Lewis acid/water scavenger. Some unpublished 2-carbonyl-1-propargyl-1H
      indoles are prepared by means of Suzuki- and Negishi-type reactions.

PMID- 17020317
TI  - Convenient method for the preparation of Weinreb amides via Pd-catalyzed
      aminocarbonylation of aryl bromides at atmospheric pressure.
AB  - [reaction: see text] The direct transformation of aryl bromides into the
      corresponding Weinreb amides via Pd-catalyzed aminocarbonylation at atmospheric
      pressure is reported.

PMID- 17020318
TI  - Effect of meso aryl substituents on the synthesis of core-modified expanded
      porphyrins.
AB  - [reaction: see text] Synthesis and characterization of core-modified
      [26]hexaphyrin (1.1.1.1.0.0). A meso aryl rubyrin isomer and a new 54pi-modified
      dodecaphyrin are reported.

PMID- 17020319
TI  - A new entry to Pd-H chemistry: catalytic asymmetric conjugate reduction of enones
      with EtOH and a highly enantioselective synthesis of warfarin.
AB  - [reaction: see text] We report here the catalytic asymmetric conjugate reduction
      of enones using ethanol as a hydride source. The reaction was carried out in the
      presence of a chiral Pd complex at ambient temperature in ethanol, and the
      desired products were obtained in high chemical yield and high
      enantioselectivity. We applied this novel reaction to the catalytic asymmetric
      synthesis of warfarin (96% ee), and on the basis of d-labeling experiments, the
      reaction mechanism is proposed.

PMID- 17020320
TI  - Synthesis and evaluation of coumermycin A1 analogues that inhibit the Hsp90
      protein folding machinery.
AB  - [structure: see text] The coumarin antibiotics are not only potent inhibitors of
      DNA gyrase but also represent the most effective C-terminal inhibitors of 90 kDa
      heat shock proteins (Hsp90) reported thus far. In contrast to the N-terminal ATP
      binding site, little is known about the Hsp90 C-terminus. In addition, very
      limited structure-activity relationships exist between this class of natural
      products and Hsp90. In this letter, the syntheses of dimeric coumarin analogues
      are presented along with their inhibitory values in breast cancer cell lines.

PMID- 17020321
TI  - Kinetic resolution of propargylic alcohols catalyzed by benzotetramisole.
AB  - [reaction: see text] Kinetic resolution of variously substituted secondary
      propargylic alcohols catalyzed by benzotetramisole (BTM) proceeds with
      selectivity factors up to 32, the highest ever achieved with nonenzymatic
      catalysts for this class of substrates.

PMID- 17020322
TI  - A versatile route to L-hexoses: synthesis of L-mannose and L-altrose.
AB  - [reaction: see text] An efficient route for the synthesis of orthogonally
      protected l-sugars has been opened up, starting from the heterocyclic
      homologating agent 1 and 2,3-O-isopropylidene-l-glyceraldehyde (2). Our synthetic
      path enables the synthesis of a 2,3-unsaturated-l-pyranoside, which can be
      suitably functionalized to afford the desired l-hexoses. In this paper, we report
      the synthesis of l-manno- and l-altro-pyranosides. Moreover, this strategy may be
      used to prepare all eight sugars and their derivatives in either enantiomeric
      form.

PMID- 17020323
TI  - Overcoming regioselectivity issues inherent in bis-Troger's base preparation.
AB  - [structure: see text] Bis-Troger's base derivatives are a new family of molecular
      tweezers. A major drawback to their study is a lack of commercially available
      precursors, ortho-nitrocarboxylic acids. A reverse synthetic strategy starting
      from known dinitrodicarboxylic acids, which circumvents this problem, is
      presented. Via this methodology regioisomeric bis-TB derivatives can be prepared
      selectively, using only common aromatic amines that are typically commercially
      available.

PMID- 17020324
TI  - A stereocontrolled access to ring-fused piperidines through a formal [2+2+2]
      process.
AB  - [reaction: see text] A formal [2+2+2] process has been devised that allows the
      stereocontrolled formation of ring-fused piperidines from allylsilanes possessing
      an oxime moiety. The cascade involves an intermolecular radical addition of an
      alpha-iodoacetate onto an allylsilane double bond, which is followed by a 5-exo
      trig cyclization onto an oxime and is completed by the formation of the amide
      bond by nucleophilic attack of the amine onto the ester function.

PMID- 17020325
TI  - Synthesis of bisbenzannulated spiroketals-model studies for a modular approach to
      rubromycins.
AB  - [reaction: see text] A highly flexible synthesis of bisbenzannulated spiroketals
      is described with additions of lithiated methoxyallene to aryl aldehydes and Heck
      reactions as key steps. Subsequent hydrogenations and ketalizations afforded the
      desired spiroketals in good yields and with predominating trans-configuration.
      With model compound 30, already bearing the fully substituted naphthyl core of
      rubromycins, the ketalization proceeded efficiently providing the expected
      product 31 and the isopropoxy compound 32. Both products are advanced model
      compounds of heliquinomycin.

PMID- 17020326
TI  - 1-naphthylpropargyl ether group: a readily cleaved and sterically minimal
      protecting system for stereoselective glycosylation.
AB  - [reaction: see text] The (1-naphthyl)propargyl group is introduced as a
      sterically unobtrusive alcohol protecting group that is cleaved in a single step
      by exposure to dichlorodicyanoquinone in wet dichloromethane. In conjunction with
      the 4,6-O-benzylidene protecting group, and the use of the sulfoxide
      glycosylation method, 3-O-naphthylpropargyl-protected mannosyl donors are
      extremely beta-selective.

PMID- 17020328
TI  - Copper-catalyzed beta-Boration of alpha,beta-unsaturated carbonyl compounds: rate
      acceleration by alcohol additives.
AB  - [reaction: see text] The efficient addition of bis(pinacolato)diboron to
      alpha,beta-unsaturated carbonyl compounds with a copper-diphosphine catalyst has
      been carried out. A dramatic rate acceleration of the reaction was realized by
      adding alcohol additives. With use of this procedure, a variety of alpha,beta
      unsaturated carbonyl compounds including conjugated substrates at the acid
      oxidation level such as esters and nitriles were reacted to give to the
      corresponding beta-boryl carbonyl compounds in high yields.

PMID- 17020327
TI  - Total synthesis of (+/-)-clavubicyclone.
AB  - [reaction: see text] The total synthesis of racemic clavubicyclone (1), which was
      isolated from Okinawan soft coral by our group, is described. The
      bicyclo[3.2.1]octane skeleton was prepared by Cope rearrangement of a
      divinylcyclopropane derivative. Three functional groups on the skeleton were
      constructed by Barton decarboxylation, Wittig reaction, and alkylation.

PMID- 17020329
TI  - Facile synthesis, fluorescence, and photochromism of novel helical pyrones and
      chromenes.
AB  - [reaction: see text] Aryl coumaryl ethylenes undergo oxidative photocyclization
      readily to yield helical pyrone-annulated condensed aromatics. The pyrones are
      conveniently converted to the corresponding photochromic
      diphenylpyrans/chromenes. Both pyrones and chromenes exhibit helicity-dependent
      fluorescence efficiency and persistence, respectively.

PMID- 17020330
TI  - Methylazacalix[4]pyridine: en route to Zn2+-specific fluoresence sensors.
AB  - [structure: see text] Owing to the electronic nature of the bridging nitrogen
      atoms which can adopt different hybridizations and form various conjugations with
      the adjacent pyridine(s), methylazacalix[4]pyridine underwent conformation and
      cavity preorganization to highly selectively bind the Zn(2+) ion. Rigidification
      and coplanarity of the macrocyclic ring led to a great enhancement of
      fluorescence of the intrinsic fluorescent host molecule.

PMID- 17020331
TI  - Stereodivergent total syntheses of precoccinelline, hippodamine, coccinelline,
      and convergine.
AB  - [structure: see text] A stereodivergent approach toward total syntheses of
      Coccinellidae defensive alkaloids is described. These syntheses feature a highly
      diastereoselective intramolecular aza-[3 + 3] annulation strategy, which
      represents a de novo approach to this family of natural products.

PMID- 17020332
TI  - Oxonitriles: a grignard addition-acylation route to enamides.
AB  - [reaction: see text] Sequential addition of three different Grignard reagents and
      pivaloyl chloride to 3-oxo-1-cyclohexene-1-carbonitrile installs four new bonds
      to generate a diverse array of cyclic enamides. Remarkably, formation of the C
      magnesiated nitrile intermediate is followed by preferential acylation by
      pivaloyl chloride rather than consumption by an in situ Grignard reagent. Rapid N
      acylation of the C-magnesiated nitrile generates an acyl ketenimine that reacts
      readily with Grignard reagents or a trialkylzincate, effectively assembling
      highly substituted, cyclic enamides.

PMID- 17020333
TI  - Metal-catalyzed regioselective oxy-functionalization of internal alkynes: an
      entry into ketones, acetals, and spiroketals.
AB  - [reaction: see text] Platinum(II) and an unusual cationic gold(I) complex were
      identified as mild catalysts for the room temperature cycloisomerization or
      tandem hydroalkoxylation/acetal formation of unactivated internal alkynols. Under
      the appropriate conditions, 5-endo, 5-exo, 6-endo, and 6-exo cycloisomerization
      modes are all available.

PMID- 17020335
TI  - Why 6-methylpentacene deconjugates but avoids the thermally allowed unimolecular
      mechanism.
AB  - [reaction: see text] Tautomeric equilibria involving hydrogen migration in
      methylacenes were explored computationally using DFT methods. As the aromatic
      system becomes more extended, the methylene isomer is predicted to become
      favored. Reasonable-looking pericyclic sigmatropic hydrogen shifts are found to
      be energetically prohibitive, and bimolecular mechanisms involving radical pair
      intermediates are energetically feasible.

PMID- 17020334
TI  - Organocatalytic highly enantioselective synthesis of secondary alpha
      hydroxyphosphonates.
AB  - [reaction: see text] The first organocatalytic cross aldol reaction of ketones
      and diethyl formylphosphonate hydrate has been realized by using readily
      available l-prolinamide as the catalyst. Secondary alpha-hydroxyphosphonates have
      been synthesized in high enantioselective (up to >99% ee) and good
      diastereoselectivity.

PMID- 17020336
TI  - Bidirectional synthesis of the central amino acid of chloptosin.
AB  - [reaction: see text] An efficient total synthesis of (2S,2'S,3aR,3'aR,8aR,8'aR)
      6,6'-dichloro-3a,3'a-dihydroxy-1,1',2,2',3,3a,3',3'a,8,8a,8',8'a-dodecahydro-5,5'
      bipyrrolo[2,3-b]indole-2,2'-dicarboxylic acid, the central amino acid component
      of chloptosin (1), is described. Starting from m-chloronitrobenzene, this C(2)
      symmetrical amino acid was synthesized by using a 14-step route, in which a Zinin
      benzidine rearrangement, intramolecular Heck reaction, and selenocyclization and
      oxidative deselenation served as key steps. The absolute stereochemistry of the
      target was confirmed by X-ray single-crystal studies on a key intermediate (17).

PMID- 17020337
TI  - Enecarbamates as imine surrogates: nucleophilic addition of 1,3-dicarbonyl
      compounds to enecarbamates.
AB  - [reaction: see text] Novel Mannich-type reactions of 1,3-dicarbonyl compounds
      with enecarbamates have been developed. Stable and storable enecarbamates work as
      surrogates of aliphatic aldehyde-derived imines, which are known to be difficult
      to isolate and store.

PMID- 17020338
TI  - Synthesis of 3-(diarylmethylenyl)oxindole by a palladium-catalyzed domino
      carbopalladation/C-H activation/C-C bond-forming process.
AB  - [reaction: see text] A highly efficient palladium-catalyzed synthesis of
      unsymmetrically substituted 3-(diarylmethylenyl)indolinones from readily
      accessible starting materials is developed. The domino reaction involves a
      sequence of intermolecular carbopalladation, C-H activation, and C-C bond
      formation. A plausible mechanistic pathway for the reaction is discussed on the
      basis of the kinetic isotope effect [K(H)/K(D) (intermolecular) = 1, K(H)/K(D)
      (intramolecular) = 2.7] as well as the electronic effect.

PMID- 17020339
TI  - Controlled conversion of isomers in a hybrid biphotochromic system.
AB  - [reaction: see text] The photochromic performance of a hybrid system connecting
      naphthopyran and dithienylethene was investigated, and the photochemistry of
      eight different isomers was explored by choosing an appropriate wavelength of
      light.

PMID- 17020340
TI  - Xylogranatins A-D: novel tetranortriterpenoids with an unusual 9,10-seco scaffold
      from marine mangrove Xylocarpus granatum.
AB  - [reaction: see text] Four novel tetranortriterpenoids, xylogranatins A-D (1-4),
      with an unusual 9,10-seco skeleton were isolated from the seeds of a Chinese
      marine mangrove Xylocarpus granatum. Their structures were determined by
      spectroscopic and chemical means. Xylogranatin A (1) featured by a unique 1,9
      oxygen bridge was confirmed by single-crystal X-ray diffraction, and xylogranatin
      D (4) with an unprecedented skeleton of C-30-C-9 linkage was postulated
      biogenetically from 3 via an alpha-hydroxyl ketone rearrangement and was
      chemically mimicked.

PMID- 17020341
TI  - Carboxylic acid catalyzed three-component aza-Friedel-Crafts reactions in water
      for the synthesis of 3-substituted indoles.
AB  - [reaction: see text] The carboxylic acid catalyzed three-component aza-Friedel
      Crafts reactions of aldehydes, primary amines, and indoles in water have been
      developed. The aza-Friedel-Crafts products could be easily transformed to various
      3-substituted indoles including biologically active compounds. This system offers
      a novel efficient method for the synthesis of 3-substituted indoles.

PMID- 17020342
TI  - Enantioselective beta-lactone formation from ketene and aldehydes catalyzed by a
      chiral oxazaborolidine.
AB  - [reaction: see text] A novel catalytic system has been developed for the
      enantioselective synthesis of beta-lactones from ketene and aldehydes.

PMID- 17020343
TI  - Ortho-arylation of benzamides.
AB  - [reaction: see text] A simple method for the direct ortho-arylation of benzoic
      acid amides has been developed. The palladium-catalyzed reactions proceed in
      trifluoroacetic acid and require the presence of stoichiometric silver acetate.
      This presents an alternative to the currently used ortho-lithiation strategies
      for the synthesis of arylated benzoic acid derivatives.

PMID- 17020344
TI  - Photoinduced cytotoxicity and thioadduct formation by a prodigiosin analogue.
AB  - [reaction: see text] The prodigiosin alkaloid 1 and the synthetic analogue 2 show
      photoinduced cytotoxicity against HL-60 cancer cells. Photoirradiation of 1 and 2
      causes photofading, photooxidation, and thioadduct formation. These results
      provide a model for the redox properties of prodigiosins that play a role in
      their biological activity and provide a new way to functionalize their
      pyrromethene entity with water-soluble thiol groups.

PMID- 17020345
TI  - The first total synthesis of (-) and (+)-2-hydroxy-24-oxooctacosanolide using an
      effective lactonization.
AB  - [structure: see text] An effective method for the total synthesis of 2-hydroxy-24
      oxooctacosanolide, a defensive salivary secretion of the African termite
      Pseudacanthotermes spiniger, has been developed. The key lactonization to form a
      29-membered ring lactone core is performed using 2-methyl-6-nitrobenzoic
      anhydride with a catalytic amount of 4-(dimethylamino)pyridine N-oxide.

PMID- 17020346
TI  - Concise assembly of the polycyclic frameworks associated with the hapalindole and
      fischerindole alkaloids.
AB  - [reaction: see text] Reaction of N-methylindole (4) with 6,6
      dibromobicyclo[3.1.0]hexane (5) in the presence of silver tetrafluoroborate
      affords conjugate 7 in 67% yield. This product can be readily elaborated to
      compounds 12b and 13b which embody the polycyclic frameworks associated with
      members of the hapalindole and fischerindole classes of alkaloids. The chiral
      auxiliary-substituted 6,6-dibromobicyclo[3.1.0]hexanes 21 and 22 react with
      indole to give adducts likely to be useful in the enantioselective total
      synthesis of the title alkaloids.

PMID- 17020347
TI  - Conformational product control in the low-temperature photochemistry of
      cyclopropylcarbenes.
AB  - [reaction: see text] Different conformers of two fused-ring
      cyclopropylchlorocarbenes are shown to undergo distinct, wavelength-selectable,
      photochemistry in low-temperature matrixes. Conformers with H and Cl syn give
      ring expansion predominantly, whereas those with H and Cl anti mainly fragment.

PMID- 17020348
TI  - Isolation and synthesis of (-)-(5S)-2-imino-1-methylpyrrolidine-5- carboxylic
      acid from Cliona tenuis: structure revision of pyrostatins.
AB  - [reaction: see text] (-)-(5S)-2-Imino-1-methylpyrrolidine-5-carboxylic acid (1),
      previously reported as the N-acetyl-beta-d-glucosaminidase inhibitor pyrostatin
      B, has been isolated from the organic extracts of the burrowing sponge Cliona
      tenuis. The structure of 1, including its absolute stereochemistry, was
      characterized from its spectral data and chemical transformations and confirmed
      by total synthesis. The synthesis of 1 reveals that the structure of pyrostatin B
      has been incorrectly assigned. Comparison of NMR spectral data strongly suggests
      that pyrostatins A and B are identical to 5-hydroxyectoine and ectoine,
      respectively.

PMID- 17020349
TI  - Total synthesis of (-)-5,6,11-trideoxytetrodotoxin and its 4-epimer.
AB  - [reaction: see text] The first total synthesis of 5,6,11-trideoxytetrodotoxin (1)
      and its 4-epimer were achieved. The synthesis is characterized by the
      stereoselective construction of the quaternary amino carbon center at C8a by an
      asymmetric transferring Strecker synthesis and the highly efficient conversion of
      cyanohydrin 4 to 1 via intramolecular cyclization reactions.

PMID- 17020350
TI  - A practical method for the synthesis of indolylaryl- and bisindolylmaleimides.
AB  - [reaction: see text] Indolylaryl and indolylheteroarylmaleimides, including
      bisindolylmaleimides, are easily prepared by the reaction of N-methylindole-3
      glyoxylamide with methyl aryl acetates in the presence of potassium tert-butoxide
      in THF.

PMID- 17020351
TI  - Room-temperature highly diastereoselective Zn-mediated allylation of chiral N
      tert-butanesulfinyl imines: remarkable reaction condition controlled
      stereoselectivity reversal.
AB  - [reaction: see text] An efficient method for the highly diastereoselective
      synthesis of chiral homoallylic amines by Zn-mediated allylation of chiral N-tert
      butanesulfinyl imines at room temperature was developed. By simply tuning the
      reaction conditions, the method allows the achievement of a highly remarkable
      opposite stereocontrol, affording the desired stereochemical outcome in good
      yield and with excellent diastereoselectivity (up to 98% dr). With N-sulfinyl
      ketimines, the corresponding quaternary carbon-containing chiral homoallylic
      amines could also be produced.

PMID- 17020355
TI  - Biography of Charles B. Harris.

PMID- 17020357
TI  - Publications of Charles B. Harris.

PMID- 17020358
TI  - Disorder-to-order transition of 1,4-dimethylnaphthalene: Formation of molecular
      complex with water and p-xylene on Al2O3 (0001).
AB  - Amorphous 1,4-dimethylnaphthalene, DMN, that can be prepared by vacuum deposition
      on Al2O3 exhibits relatively intense excimer fluorescence. Upon heating the
      surface, the adlayer undergoes a disorder-to-order transition, signaled by a
      decrease in excimer and an increase in monomer fluorescence. In a bilayer
      experiment, water, which has a lower desorption temperature than DMN, is vacuum
      deposited first, followed by DMN. When the surface is heated, water percolates
      through the DMN and forms a molecular H2O-DMN surface complex that desorbs
      simultaneously. The stoichiometric ratio of this complex was determined to be
      (DMN)(1.4+/-0.3).H2O. When the bilayer was formed with p-xylene, a complex of DMN
      p-xylene was observed that had the stoichiometry of (DMN)(7.9+/-1).p-xylene.

PMID- 17020359
TI  - Quantitative characterization of changes in dynamical behavior for single
      particle tracking studies.
AB  - Single-particle tracking experiments have been used widely to study the
      heterogeneity of a sample. Segments with dissimilar diffusive behaviors are
      associated with different intermediate states, usually by visual inspection of
      the tracking trace. A likelihood-based, systematic approach is presented to
      remove this incertitude. Maximum likelihood estimators are derived for the
      determination of diffusion coefficients. A likelihood ratio test is applied to
      the localization of the changes in them. Simulations suggest that the proposed
      procedure is statistically robust and is able to quantitatively recover time
      dependent changes in diffusion coefficients even in the presence of large
      measurement noise.

PMID- 17020361
TI  - Ultrafast hot-carrier dynamics at chemically modified Ge interfaces probed by
      SHG.
AB  - Time-resolved second-harmonic generation (SHG) was used to study the hot-carrier
      dynamics and nonlinear optical properties of S-terminated and Cl-terminated
      Ge(111) interfaces on the femtosecond time scale. The hot-carrier second-order
      nonlinear optical susceptibilities were determined to be 720 +/- 50 times greater
      than the valence-band second-order nonlinear optical susceptibilities for the
      Ge(111)-S system and 880 +/- 100 times greater in the Ge(111)-Cl system.
      Furthermore, the ground- and excited-state second-order nonlinear optical
      susceptibilities are suggested to be out of phase for Ge(111)-S and Ge(111)-Cl
      systems, leading to a pump-induced decrease in the SHG signal as opposed to the
      increase in the SHG signal observed in the Ge(111)-GeO2 system. Although the SHG
      response reaches a steady state in 415 +/- 90 fs in the Ge(111)-GeO2 system, a
      faster response is observed in the Ge(111)-S system, 220 +/- 85 fs, and in the
      Ge(111)-Cl system, 172 +/- 50 fs. This suggests significantly faster carrier
      cooling at the Ge(111)-Cl and Ge(111)-S interfaces, with significant implications
      for hot-carrier mediated device degradation, and migration to high-K dielectrics.

PMID- 17020360
TI  - Coherent electronic and nuclear dynamics for charge transfer in 1-ethyl-4
      (carbomethoxy)pyridinium iodide.
AB  - Although polaronic interactions and states abound in charge transfer processes
      and reactions, quantitative and separable determination of electronic and nuclear
      relaxation is still challenging. The present paper employs the amplitudes,
      polarizations, and phases of four-wave mixing signals to obtain unique dynamical
      information on relaxation processes following photoinduced charge transfer
      between iodide and 1-ethyl-4-(carbomethoxy)pyridinium ions. Pump-probe signal
      amplitudes reveal the coherent coupling of an underdamped 115 cm(-1) nuclear mode
      to the charge transfer excitation. Assignments of this recurrence to
      intramolecular vibrational modes of the acceptor and to modulation of the
      intermolecular donor-acceptor distance are discussed on the basis of a high-level
      density functional theory normal-mode analysis and previously observed wave
      packet dynamics of solvated molecular iodine. Nuclear relaxation of the acceptor
      induces sub-picosecond decay of the pump-probe polarization anisotropy from an
      initial value of 0.4 to an asymptotic value of -0.05. Electronic structure
      calculations suggest that relaxation along the torsional coordinate of the ethyl
      group is the origin of the anisotropy decay. Electric-field-resolved transient
      grating (EFR-TG) signal fields are obtained by spectral interferometry with a
      diffractive optic based interferometer. These measurements show that the signal
      phase and amplitude possess similar dynamics. Model calculations are used to
      demonstrate how the EFR-TG signal phase yields unique information on transient
      material resonances located outside the laser pulse spectrum. This effect can be
      rationalized in that the real and imaginary parts of the nonlinear polarization
      are related by the Kramers-Kronig transformation, which allows the dispersive
      component of the polarization response to exhibit spectral sensitivity over a
      larger frequency range than that defined by the absorption bandwidth.

PMID- 17020362
TI  - Molecular rotation at negatively charged surfactant/aqueous interfaces.
AB  - The effect of charge on the rotational dynamics of the molecular probe coumarin
      314 (C314) at air/water interfaces covered with the negatively charged surfactant
      sodium dodecyl sulfate (SDS) was investigated using femtosecond time-resolved
      second harmonic spectroscopy. The out-of-plane orientational time constant at the
      highest SDS surface coverage of 100 A2 per molecule is 383 +/- 9 ps. The
      rotational dynamics is slower than at the air/water interface where the out-of
      plane reorientational time constant is 336 +/- 6 ps. At the air/water interface
      the rotational dynamics is over three times slower than the bulk orientational
      diffusion time of 100 ps. The relatively small effect of the surfactant charge
      density on the C314 rotation time constant is surprising, considering the marked
      dependence of the C314 orientation, spectra, and surfactant phase diagram on
      surfactant density.

PMID- 17020363
TI  - Photoelectron spectroscopy and DFT calculations of easily ionized quadruply
      bonded Mo2(4+) compounds and their bicyclic guanidinate precursors.
AB  - A series of five bicyclic guanidinate compounds containing various combinations
      of five- and six-membered rings and substituted alkyl groups have been shown by
      photoelectron spectroscopy to be easily ionized, with the one having two six
      membered rings and four ethyl groups being the most easily ionized. The
      corresponding anions are capable of forming paddlewheel compounds having
      quadruply bonded Mo2(4+) units which are also easy to ionize. The most easily
      ionized compound is the ethyl-substituted Mo2(TEhpp)4 complex which has a broad
      first ionization band centered around 4.27 +/- 0.03 eV and an ionization onset at
      the very low energy of 3.93 +/- 0.03 eV. Even the compound with ligands
      containing two five-membered rings, which favors a long Mo-Mo separation because
      of the large ligand bite, has an ionization energy (4.78 eV) that is less than
      those of well-known organometallic reducing agents such as (eta5-C9Me7)2Co and
      (eta5-C5Me5)2Cr.

PMID- 17020364
TI  - Anisotropic diffusion of elongated and aligned polymer chains in a nematic
      solvent.
AB  - The translational diffusion constant, D, of a polymer solute in a single-domain,
      nematic liquid crystal solvent (5CB) is measured in directions parallel and
      perpendicular to the nematic director using a fluorescence two-beam, cross
      correlation technique. The solute under investigation is the stiff, conjugated
      polymer, MEH-PPV. The ratio D parallel/D perpendicular) of diffusion constants
      (parallel and perpendicular to the director) is observed to be 1.9 +/- 0.3. This
      is surprisingly small considering that MEH-PPV is known to be both elongated and
      highly aligned along the liquid crystal director of 5CB. We therefore argue that
      the structural order parameter of the solvent governs the anisotropy of the
      diffusion of the solute.

PMID- 17020365
TI  - High-resolution apertureless near-field optical imaging using gold nanosphere
      probes.
AB  - An apertureless near-field scanning optical microscope (ANSOM) that utilizes the
      enhanced field around a gold nanosphere, which is attached to the end of an
      atomic force microscope (AFM) tip, is used to image the local dielectric constant
      of the patterned metallic surfaces and local electric field around plasmonic
      nanosphere samples. A colloidal gold nanosphere (approximately 50 nm diameter) is
      linked to the extremity of the conventional etched-silicon probe. The scattering
      of laser radiation (633 or 532 nm) is modulated by the oscillating nanosphere
      functionalized silicon tip, and the scattered radiation is detected. The approach
      curve (scattering intensity as a function of the tip-sample distance), the
      polarization dependence (scattering intensity as a function of the excitation
      polarization direction), and ANSOM image contrast confirm that the spherical
      nanosphere attached to the silicon tip acts as a point dipole that interacts with
      the sample surface via a dipole-dipole coupling, in which the dipole created by
      the field at the tip interacts with its own image dipole in the sample. The image
      obtained with the nanoparticle functionalized tip provides a dielectric map of
      the sample surface with a spatial resolution better than 80 nm. In addition, we
      show that the functionalized tip is capable of imaging the local electric field
      distribution above the plasmonic nanosphere samples. Overall, the result shows
      that high-resolution ANSOM is possible without the aid of the lightning-rod
      effect. With an improved tip-fabrication method, we believe that the method can
      provide a versatile high-resolution chemical imaging that is not available from
      usual forms of ANSOM.

PMID- 17020366
TI  - Light-harvesting in carbonyl-terminated phenylacetylene dendrimers: The role of
      delocalized excited States and the scaling of light-harvesting efficiency with
      dendrimer size.
AB  - The photophysics of a family of conjugated phenylacetylene (PA) light-harvesting
      dendrimers are studied using steady-state and time-resolved optical spectroscopy.
      The dendrimers consist of a substituted PA core surrounded by meta-branched PA
      arms. The total number of PA moieties ranges from 3 (first generation) to 63
      (fifth generation). By using an alcohol/ketone substituent at the dendrimer core,
      we avoid through-space Forster transfer from the peripheral PA donors to the core
      acceptor (in this case, the carbonyl group), which simplifies the analysis of
      these molecules relative to the perylene-terminated molecules studied previously.
      The delocalized excited states previously identified in smaller dendrons are seen
      in these larger dendrimers as well, and their influence on the intersite
      electronic energy transfer (EET) is analyzed in terms of a point-dipole Forster
      model. We find that these new delocalized states can both enhance EET (by
      decreasing the spatial separation between donor and acceptor) and degrade it (by
      lowering the emission cross section and shifting the energy, resulting in poorer
      spectral overlap between donor and acceptor). The combination of these two
      effects leads to a calculated intersite transfer time of 6 ps, in reasonable
      agreement with the 5-17 ps range obtained from experiment. In addition to
      characterizing the electronic states and intersite energy transfer times, we also
      examine how the overall light-harvesting efficiency scales with dendrimer size.
      After taking the size dependence of other nonradiative processes, such as excimer
      formation, into account, the overall dendrimer quenching rate k(Q) is found to
      decrease exponentially with dendrimer size over the first four generations. This
      exponential decrease is predicted by simple theoretical considerations and by
      kinetic models, but the dependence on generation is steeper than expected based
      on those models, probably due to increased disorder in the larger dendrimers. We
      discuss the implications of these results for dendrimeric light-harvesting
      structures based on PA and other chemical motifs.

PMID- 17020367
TI  - Intramolecular hydrogen bonding in 1,8-dihydroxyanthraquinone, 1
      aminoanthraquinone, and 9-hydroxyphenalenone studied by picosecond time-resolved
      fluorescence spectroscopy in a supersonic jet.
AB  - We investigated spectroscopic and dynamic fluorescence properties of the S1 <--
      S0 transitions of three intramolecularly hydrogen-bonded molecules, 1,8
      dihydroxyanthraquinone (1,8-DHAQ), 1-aminoanthraquinone (1-AAQ), and 9
      hydroxyphenalenone (9-HPA), by determining their fluorescence excitation spectra
      and state-selective fluorescence lifetimes under supersonic jet conditions.
      Moreover, ab initio calculations were performed on one-dimensional hydrogen
      transfer potential energy curves in both the S0 and the S1 state and on S0 and S1
      minimum energy conformations and normal-mode frequencies at different levels of
      theory (HF/6-31G(d,p) and B3LYP/6-31G(d,p), CIS/6-31G(d,p) and TDDFT/6
      31G(d,p)//CIS/6-31G(d,p), respectively). In line with calculations based on the
      theory of "atoms in molecules" (AIM), we suggest that the fluorescence properties
      of 1-AAQ are associated with a single-minimum-type potential. The nonradiative
      relaxation mechanism is attributed to internal conversion to the S0 state. For
      1,8-DHAQ, we suggest in agreement with previous findings that the fluorescence
      bands below approximately 600 cm(-1) are due to transitions originating in the
      9,10-quinone well, whereas the bands above approximately 600 cm(-1) are due to
      transitions originating in the proton-transferred 1,10-quinone well, thus
      confirming the assumption that 1,8-DHAQ possesses a double-minimum-type S1
      potential. On the basis of our ab initio calculations, we suggest that the
      fluorescence originating in the 1,10-quinone well is due to vertical absorption
      into the 9,10-quinone well and subsequent fast ESIPT above the hydrogen transfer
      barrier. For 9-HPA, only the frequency-domain measurements give tentative
      evidence of the presence of a pronounced double-minimum-type potential. The rapid
      nonradiative relaxation mechanism as revealed by fluorescence lifetime
      measurements is attributed to intersystem crossing to a triplet state.

PMID- 17020368
TI  - Efficient CO oxidation at low temperature on Au(111).
AB  - The rate of CO oxidation to CO2 depends strongly on the reaction temperature and
      characteristics of the oxygen overlayer on Au(111). The factors that contribute
      to the temperature dependence in the oxidation rate are (1) the residence time of
      CO on the surface, (2) the island size containing Au-O complexes, and (3) the
      local properties, including the degree of order of the oxygen layer. Three
      different types of oxygen--defined as chemisorbed oxygen, a surface oxide, and a
      bulk oxide--are identified and shown to have different reactivity. The relative
      populations of the various oxygen species depend on the preparation temperature
      and the oxygen coverage. The highest rate of CO oxidation was observed for an
      initial oxygen coverage of 0.5 monolayers that was deposited at 200 K where the
      density of chemisorbed oxygen is maximized. The rate decreases when two
      dimensional islands of the surface oxide are populated and further decreases when
      three-dimensional bulk gold oxide forms. Our results are significant for
      designing catalytic processes that use Au for CO oxidation, because they suggest
      that the most efficient oxidation of CO occurs at low temperature--even below
      room temperature--as long as oxygen could be adsorbed on the surface.

PMID- 17020369
TI  - Generalized solvation heat capacities.
AB  - The partial molar heat capacity associated with a constant-pressure solvation
      process is extended to define a total of six generalized solvation heat
      capacities, each of which contain unique physical information. These arise from
      all the possible cross derivatives of the reversible heat of solvation (with
      respect to T and N), each evaluated at either constant pressure or constant
      volume. The resulting quantities may be interconverted using expressions that
      depend on the solvent equation of state and the solute partial molar volume.
      Moreover, contributions to each of the solvation heat capacities arising from the
      temperature dependence of the solute-solvent interaction energy and the solvent
      reorganization energy (at either constant pressure or constant volume) are
      formally identified. For the self-solvation of a molecule in its own pure fluid,
      the latter quantities may be extracted directly from experimental data, while for
      more general solvation processes additional input is required, either from
      computer simulation or from theoretical approximations. The results are used to
      experimentally quantify the generalized heat capacities pertaining to the self
      solvation of xenon, difluoromethane, n-hexane, and water, as well as the
      hydration of xenon, cyclohexane, and three hard sphere solutes (of about the same
      size as water, xenon, and cyclohexane).

PMID- 17020370
TI  - Effective Hamiltonian models and unimolecular decomposition.
AB  - Partitioning Hilbert space into two subspaces by using orthogonal projection
      operators yields compact forms for effective Hamiltonians for each of the
      subspaces. When one (the Q space) contains molecular bound states and the other
      (the P space) contains dissociative continua, a simple form for the non-Hermitian
      Q-space effective Hamiltonian, H(eff), can be obtained, subject to reasonable
      approximations. Namely, H(eff) = H0 - ivariant Planck's/2pi Gamma/2, where H0 is
      Hermitian, and the width operator variant Planck's/2pi Gamma accounts for
      couplings of the Q-space levels to the P-space continua. The P/Q partitioning
      procedure has been applied in many areas of atomic, molecular, and nuclear
      physics with widespread success. Inputting into this formalism ideas from random
      matrix theory in order to model independent open channels yields the random
      matrix H(eff) model. Despite numerous efforts, this model has failed to model
      satisfactorily the statistical transition-state theory of unimolecular
      decomposition (hereafter referred to as TST) in the regime of overlapping
      resonances, where nearly all such reactions occur. All statistical models of
      unimolecular decomposition are premised on rapid intramolecular vibrational
      redistribution (IVR) for a given set of good quantum numbers. The phase space
      thus accessed results in a threshold reaction rate of 1/h rho, and for K
      independent open channels, the rate is K/h rho. This reaction rate corresponds to
      a resonance width of K/2pi rho, and when K increases, the resonances (which are
      rho(-1) apart) overlap. In this regime, the random matrix H(eff) model fails
      because it does not introduce independent open channels. To illustrate the source
      of the problem, an analysis is carried out of a simple model that is obviously
      and manifestly inconsistent with TST. This model is solved exactly, and it is
      then put in the form of the random matrix H(eff) model, illustrating the one-to
      one correspondence. This reveals the deficiencies of the latter. In manipulating
      this model into the form H0 - ivariant Planck's/2pi Gamma/2, it becomes clear
      that the independent open channels in the random matrix H(eff) model are
      inconsistent with TST. Rather, this model is one of gateway states (i.e., bound
      states that are coupled to their respective continua as well as to a manifold of
      zero-order bound states, none of which are coupled directly to the continua).
      Despite the fact that the effective Hamiltonian method is, by itself, beyond
      reproach, the random matrix H(eff) model is flawed as a model of unimolecular
      decomposition in several respects, most notably, bifurcations of the
      distributions of resonance widths in the regime of overlapping resonances.

PMID- 17020371
TI  - Revisiting Bohr's semiclassical quantum theory.
AB  - Bohr's atomic theory is widely viewed as remarkable, both for its accuracy in
      predicting the observed optical transitions of one-electron atoms and for its
      failure to fully correspond with current electronic structure theory. What is not
      generally appreciated is that Bohr's original semiclassical conception differed
      significantly from the Bohr-Sommerfeld theory and offers an alternative
      semiclassical approximation scheme with remarkable attributes. More specifically,
      Bohr's original method did not impose action quantization constraints but rather
      obtained these as predictions by simply matching photon and classical orbital
      frequencies. In other words, the hydrogen atom was treated entirely classically
      and orbital quantized emerged directly from the Planck-Einstein photon
      quantization condition, E = h nu. Here, we revisit this early history of quantum
      theory and demonstrate the application of Bohr's original strategy to the three
      quintessential quantum systems: an electron in a box, an electron in a ring, and
      a dipolar harmonic oscillator. The usual energy-level spectra, and optical
      selection rules, emerge by solving an algebraic (quadratic) equation, rather than
      a Bohr-Sommerfeld integral (or Schroedinger) equation. However, the new
      predictions include a frozen (zero-kinetic-energy) state which in some (but not
      all) cases lies below the usual zero-point energy. In addition to raising
      provocative questions concerning the origin of quantum-chemical phenomena, the
      results may prove to be of pedagogical value in introducing students to quantum
      mechanics.

PMID- 17020372
TI  - Fifth-order Raman spectroscopy of liquid benzene: experiment and theory.
AB  - The heterodyned fifth-order Raman response of liquid benzene has been measured
      and characterized by exploiting the passive-phase stabilization of diffractive
      optics. This result builds on our previous work with liquid carbon disulfide and
      extends the spectroscopy to a new liquid for the first time. The all-parallel and
      Dutch Cross polarization tensor elements are presented for both the experimental
      results and a finite-field molecular dynamics simulation. The overall response
      characteristics are similar to those of liquid carbon disulfide: a complete lack
      of signal along the pump delay, an elongated signal along the probe delay, and a
      short-lived signal along the time diagonal. Of particular interest is the change
      in phase between the nuclear and electronic response along the probe delay and
      diagonal which is not seen in CS2. Good agreement is achieved between the
      experiment and the finite-field molecular dynamics simulation. The measurement of
      the low-frequency Raman two-time delay correlation function indicates the
      intermolecular modes of liquid benzene to be primarily homogeneously broadened
      and that the liquid loses its nuclear rephasing ability within 300 fs. This rapid
      loss of nuclear correlations indicates a lack of modal character in the low
      frequency motions of liquid benzene. This result is a validation of the general
      nature of the technique and represents an important step forward with respect to
      the use of nonlinear spectroscopy to directly access information on the
      anharmonic motions of liquids.

PMID- 17020373
TI  - Microsecond melting of a folding intermediate in a coiled-coil peptide, monitored
      by T-jump/UV Raman spectroscopy.
AB  - A truncated version of the GCN4 coiled-coil peptide has been studied by
      ultraviolet resonance Raman (UVRR) spectroscopy with 197 nm excitation, where
      amide modes are optimally enhanced. Although the CD melting curve could be
      satisfactorily described with a two-state transition having Tm = 30 degrees C,
      singular value decomposition of the UVRR data yielded three principal components,
      whose temperature dependence implicates an intermediate form between the folded
      and unfolded forms, with formation and melting temperatures of 10 and 40 degrees
      C. Two alpha-helical amide III bands, at 1340 and 1300 cm(-1), melted out
      selectively at 10 and 40 degrees C, respectively, and are assigned to hydrated
      and unhydrated helical regions. The hydrated regions are proposed to be melted in
      the intermediate form, while the unhydrated regions are intact. Time-resolved
      UVRR spectra following laser-induced temperature jumps revealed two relaxations,
      with time constants of 0.2 and 15 mus. These are suggested to reflect the melting
      times of hydrated and unhydrated helices. The unhydrated helical region may be
      associated with a 14-residue "trigger" sequence that has been identified in the C
      terminal half of GCN4. Dehydration of helices may be a key step in the folding of
      coiled-coils.

PMID- 17020374
TI  - Second harmonic generation and confined acoustic phonons in highly excited
      semiconductor nanocrystals.
AB  - The photo-induced enhancement of second harmonic generation and the effect of
      nanocrystal shape and pump intensity on confined acoustic phonons in
      semiconductor nanocrystals have been investigated with time-resolved scattering
      and absorption measurements. The second harmonic signal showed a sublinear
      increase of the second-order susceptibility with respect to the pump pulse
      energy, indicating a reduction of the effective one-electron second-order
      nonlinearity with increasing electron-hole density in the nanocrystals. The
      coherent acoustic phonons in spherical and rod-shaped semiconductor nanocrystals
      were detected in a time-resolved absorption measurement. Both nanocrystal
      morphologies exhibited oscillatory modulation of the absorption cross section,
      the frequency of which corresponded to their coherent radial breathing modes. The
      amplitude of the oscillation also increased with the level of photoexcitation,
      suggesting an increase in the amplitude of the lattice displacement as well.

PMID- 17020375
TI  - Conformations of N-acetyl-L-prolinamide by two-dimensional infrared spectroscopy.
AB  - Femtosecond two-dimensional infrared (2D IR) spectroscopy has been applied to
      study the conformations of a model dipeptide, N-acetyl-L-prolinamide (AcProNH2)
      in deuterated chloroform (CDCl3). Spectral features in the amide-I and -II
      regions are obtained by rephasing (R), nonrephasing (NR), and reverse photon echo
      (RPE) pulse sequences with two polarization conditions. The 2D spectra obtained
      by the RPE and NR sequences with (0, 0, 0, 0) polarization reveal new spectral
      features associated with the multiple conformers of AcProNH2 that are difficult
      to discern using R sequence and linear-IR spectroscopy. The high resolving power
      of the RPE sequence comes from destructive interference between the positive and
      negative peaks of nearby vibrators, similar to the NR sequence. The RPE response
      functions that are useful for 2D spectral simulations are evaluated, including
      the effects of vibrational frequency correlations. The 2D spectra obtained with
      (45, -45, 90, 0) polarization exhibit clear cross-peak patterns in the off
      diagonal region for the R and RPE sequences but in the diagonal region for the NR
      sequence. These patterns, free from strong diagonal contributions, are crucial
      for structure determination. DFT calculations, normal-mode analysis, Hessian
      matrix reconstruction, and vibrational exciton Hamiltonian diagonalization yield
      molecular parameters needed for quantitative simulations of 2D spectra: angles
      between transition dipoles, coupling constants, and off-diagonal anharmonicities
      of the amide-I and -II modes are obtained for solvated trans-C7 and cis
      structures and for gas-phase trans conformers in the region of phi = -120 degrees
      to 0 degrees and psi = -100 degrees to 180 degrees in the Ramachandran space.
      Systematic simulations based on a 4:1 population ratio of the solvated trans-C7
      and cis structures reproduce well the 2D spectral features obtained at both
      polarization conditions. However, better agreement between the experimental and
      simulated cross-peak patterns can be reached if the dihedral angles of the major
      trans conformer are close to (phi, psi) = (-80 degrees , 100 degrees ). Our
      results suggest that the major conformer of AcProNH2 in CDCl3 deviates from the
      gas-phase global minimum, the trans-C7 form, to an extended intermediate between
      the C7 and polyproline-II structure. These results are discussed in relationship
      with earlier findings obtained by NMR, transient IR studies, and MD simulations.

PMID- 17020376
TI  - On the electron transfer mechanism between cytochrome C and metal electrodes.
      Evidence for dynamic control at short distances.
AB  - Cytochrome c was coordinatively bound to self-assembled monolayers of pyridine
      terminated alkanethiols on Au and Ag electrodes. The mechanism of heterogeneous
      electron transfer of the immobilized protein was investigated by cyclic
      voltammetry and time-resolved surface-enhanced resonance Raman
      spectroelectrochemistry. The temperature, distance, and overpotential
      dependencies of the electron transfer rates indicate a change of mechanism from a
      tunneling controlled reaction at long distances (thicker films) to a
      solvent/protein friction controlled reaction at smaller distances (thinner
      films).

PMID- 17020377
TI  - Rotationally resolved electronic spectra of 2- and 3-methylanisole in the gas
      phase: a study of methyl group internal rotation.
AB  - Rotationally resolved fluorescence excitation spectra of several torsional bands
      in the S1 <-- S0 electronic spectra of 2-methylanisole (2MA) and 3-methylanisole
      (3MA) have been recorded in the collision-free environment of a molecular beam.
      Some of the bands can be fit with rigid rotor Hamiltonians; others exhibit
      perturbations produced by the coupling between the internal rotation of the
      methyl group and the overall rotation of the entire molecule. Analyses of these
      data show that 2MA and 3MA both have planar heavy-atom structures; 2MA has trans
      disposed methyl and methoxy groups, whereas 3MA has both cis- and trans-disposed
      substituents. The preferred orientations (staggered or eclipsed) in two of the
      conformers and the internal rotation barriers of the methyl groups in all three
      conformers change when they are excited by light. Additionally, the values of the
      barriers opposing their motion depend on the relative positions of the
      substituent groups, in both electronic states. In contrast, no torsional motions
      of the attached methoxy groups were detected. Possible reasons for these
      behaviors are discussed.

PMID- 17020378
TI  - Optical properties of Au-Ag nanoboxes studied by single nanoparticle
      spectroscopy.
AB  - The optical properties of two Au-Ag nanobox samples with average edge lengths of
      44 and 58 nm and wall thicknesses of 6 and 8 nm, respectively, have been studied
      by single particle spectroscopy. The measurements gave an average line width of
      Gamma = 306 +/- 7 meV with a standard deviation of sigma = 30 meV for the 44-nm
      boxes, and Gamma = 350 +/- 9 meV with sigma = 35 meV for the 58-nm boxes. These
      line widths are much broader than those of gold nanorods with comparable
      resonance energies. The increased broadening is attributed to a combination of
      surface scattering of electrons, as well as increased radiation damping for the
      nanoboxes. Discrete dipole approximation calculations have been performed with
      and without surface scattering of electrons to compare with the experimental
      spectra. The calculations confirm that both electron-surface scattering and
      radiation damping are important effects in this system.

PMID- 17020380
TI  - Synthesis, characterization, and tunable optical properties of hollow gold
      nanospheres.
AB  - Nearly monodisperse hollow gold nanospheres (HGNs) with tunable interior and
      exterior diameters have been synthesized by sacrificial galvanic replacement of
      cobalt nanoparticles. It is possible to tune the peak of the surface plasmon band
      absorption between 550 and 820 nm by carefully controlling particle size and wall
      thickness. Cobalt particle size is tunable by simultaneously changing the
      concentration of sodium borohydride and sodium citrate, the reducing and capping
      agent, respectively. The thickness of the gold shell can be varied by carefully
      controlling the addition of gold salt. With successful demonstration of ensemble
      as well as single HGN surface-enhanced Raman scattering, these HGNs have shown
      great potential for chemical and biological sensing applications, especially
      those requiring nanostructures with near-IR absorption.

PMID- 17020379
TI  - Magnetically assisted and accelerated self-assembly of strawberry-like
      nano/microparticles.
AB  - Precisely controlling multiple components of functional materials with well
      defined shapes and dimensions on the micro/nanometer scale promises to provide
      new electronic, magnetic, mechanical, and optical properties for novel sensors,
      circuits, and other materials application. Here for the first time we introduce a
      novel method to reliably pattern strawberry-like microspheres by employing
      magnetically directed and accelerated self-assembly of nano/microparticles in
      aqueous solution, without the use of a template (such as molds or grooves). The
      results show that 100-1000 nm paramagnetic "decorating particles" rapidly self
      assembled onto the surface of fluorescent 4-5 mum spherical magnetized "core
      particles", producing strawberry-like particles with stable and precisely
      arranged microstructures. Magnetic CrO2 nanorods, approximately 60 nm in diameter
      and 300 nm long, attached to the nonplanar surface of the 4-5 microm polystyrene
      core microspheres, serve as nanometer magnetic traps, so as to attract and
      confine paramagnetic decorating particles. The ease and speed, with which these
      particles can be fabricated with the aid of magnetic force, and the flexibility
      to tailor their chemical and physical properties through the choice of decorating
      particles, should facilitate their use for practical application in materials
      science, biology, and technology.

PMID- 17020381
TI  - Photoionization and photofragmentation of SF6 in helium nanodroplets.
AB  - The photoionization of He droplets doped with SF6 was investigated using tunable
      vacuum ultraviolet (VUV) synchrotron radiation from the Advanced Light Source
      (ALS). The resulting ionization and photofragmentation dynamics were
      characterized using time-of-flight mass spectrometry combined with photofragment
      and photoelectron imaging. Results are compared to those of gas-phase SF6
      molecules. We find dissociative photoionization to SF5+ to be the dominant
      channel, in agreement with previous results. Key new findings are that (a) the
      photoelectron spectrum of the SF6 in the droplet is similar but not identical to
      that of the gas-phase species, (b) the SF5+ photofragment velocity distribution
      is considerably slower upon droplet photoionization, and (c) fragmentation to
      SF4+ and SF3+ is much less than in the photoionization of bare SF6. From these
      measurements we obtain new insights into the mechanism of SF6 photoionization
      within the droplet and the cooling of the hot photofragment ions produced by
      dissociative photoionization.

PMID- 17020382
TI  - State preparation and excited electronic and vibrational behavior in hemes.
AB  - The temporally overlapping, ultrafast electronic and vibrational dynamics of a
      model five-coordinate, high-spin heme in a nominally isotropic solvent
      environment has been studied for the first time with three complementary
      ultrafast techniques: transient absorption, time-resolved resonance Raman Stokes,
      and time-resolved resonance Raman anti-Stokes spectroscopies. Vibrational
      dynamics associated with an evolving ground-state species dominate the
      observations. Excitation into the blue side of the Soret band led to very rapid
      S2 --> S1 decay (sub-100 fs), followed by somewhat slower (800 fs) S1 --> S0
      nonradiative decay. The initial vibrationally excited, non-Boltzmann S0 state was
      modeled as shifted to lower energy by 300 cm(-1) and broadened by 20%. On a
      approximately 10 ps time scale, the S0 state evolved into its room-temperature,
      thermal distribution S0 profile largely through VER. Anti-Stokes signals
      disappear very rapidly, indicating that the vibrational energy redistributes
      internally in about 1-3 ps from the initial accepting modes associated with S1 -
      > S0 internal conversion to the rest of the macrocycle. Comparisons of anti
      Stokes mode intensities and lifetimes from TRARRS studies in which the initial
      excited state was prepared by ligand photolysis [Mizutani, T.; Kitagawa, T.
      Science 1997, 278, 443, and Chem. Rec. 2001, 1, 258] suggest that, while
      transient absorption studies appear to be relatively insensitive to initial
      preparation of the electronic excited state, the subsequent vibrational dynamics
      are not. Direct, time-resolved evaluation of vibrational lifetimes provides
      insight into fast internal conversion in hemes and the pathways of subsequent
      vibrational energy flow in the ground state. The overall similarity of the model
      heme electronic dynamics to those of biological systems may be a sign that the
      protein's influence upon the dynamics of the heme active site is rather subtle.

PMID- 17020383
TI  - The rectified second law of thermodynamics.
AB  - Equilibrium thermodynamics is combined with Jarzynski's irreversible work theorem
      to quantify the excess entropy produced by irreversible processes. The resulting
      rectified form of the second law parallels the first law, in the sense that it
      facilitates the experimental measurement of excess entropy changes resulting from
      irreversible work and heat exchanges, just as the first law quantifies energy
      changes produced by either reversible or irreversible work and heat exchanges.
      The general form of the rectified second law is further applied to a broad class
      of quasi-static irreverisble (QSI) processes, for which all of the thermodynamic
      functions of both the system and surroundings remain continuously well-defined,
      thus facilitating excess entropy measurements by integrating exact differential
      functions along QSI paths. The results are illustrated by calculating the
      mechanical and thermal excess entropy produced by the irreversible unfolding of
      an RNA molecule.

PMID- 17020384
TI  - Adsorption energies, inter-adsorbate interactions, and the two binding sites
      within monolayer benzene on Ag(111).
AB  - The adsorption of monolayer and multilayer benzene on the Ag(111) surface was
      characterized using temperature programmed desorption (TPD). TPD spectra revealed
      two broad peaks at approximately 205 and approximately 150 K at submonolayer
      coverage and a sharper, multilayer peak at 140 K. Analysis of the coverage
      dependent shape and shift of the two submonolayer peaks has resulted in their
      assignment to desorption from two different binding geometries on threefold
      hollow sites with symmetries C(3v)(sigma d) and C(3v)(sigma v). The TPD peak
      analysis incorporated inter-adsorbate repulsive interaction that resulted from
      the local dipole moment at the adsorption site induced by the adsorbate-surface
      charge transfer bonding. The analysis has yielded desorption energies of 54.9 +/-
      0.8 and 50.4 +/- 0.4 kJ/mol for the C(3v)(sigma d) and C(3v)(sigma v)
      configurations, respectively. The interface dipole and polarizability of the
      benzene-silver complex have been determined to be 5.4 +/- 1.8 D and 14 +/- 10 A3,
      respectively. Repulsive interactions in the monolayer were found to lower the
      desorption energy from the zero-coverage value by 14.8 kJ/mol. Leading edge
      analysis of the multilayer peak yielded a desorption energy of 40.9 +/- 0.7
      kJ/mol.

PMID- 17020385
TI  - Analysis of titanium nanoparticles created by laser irradiation under liquid
      environments.
AB  - The results of studies of the formation of various titanium-based nanoparticles
      by laser ablation of a titanium rod in liquid environments comprised of water,
      ethanol, 2-propanol, and n-hexane are reported. The effect of fluence on
      nanoparticle characteristics was studied by ablation with a 532 nm Nd:YAG
      operating at 10 Hz, showing that mean particle size and the size distribution
      increase with increasing laser intensity. The solvent plays a crucial role in the
      nature of the nanoparticles, as solvent components are incorporated into the
      nanoparticles during formation. Titanium nanoparticles formed in oxygen-rich
      solvents incorporate oxygen, while those formed in a carbon-rich environment are
      found to contain carbon. The nanoparticles created in their respective liquid
      environments are very stable, maintain their character over time, and remain in
      solution for months after creation.

PMID- 17020386
TI  - Excitation of magnetization using a modulated radiation damping field.
AB  - In this work, pulsed-field gradients are used to modulate the radiation damping
      field generated by the detection coil in an NMR experiment in order that spins
      with significantly different chemical shifts can affect one another via the
      radiation damping field. Experiments performed on solutions of acetone/water and
      acetone/DMSO/water demonstrate that spins with chemical shift differences much
      greater than the effective radiation damping field strength can still be coupled
      by modulating the radiation damping field. Implications for applications in high
      field NMR and for developing sensitive magnetization detectors are discussed.

PMID- 17020387
TI  - Vibrational relaxation of CN stretch of pseudo-halide anions (OCN-, SCN-, and
      SeCN-) in polar solvents.
AB  - The vibrational relaxation dynamics of pseudo-halide anions XCN- (X = O, S, Se)
      in polar solvents were studied to understand the effect of charge on solute-to
      solvent intermolecular energy transfer (IET) and solvent assisted intramolecular
      vibrational relaxation (IVR) pathways. The T1 relaxation times of the CN stretch
      in these anions were measured by IR pump/IR probe spectroscopy, in which the 0-1
      transition was excited, and the 0-1 and 1-2 transitions were monitored to follow
      the recovery of the ground state and decay of the excited state. For these anions
      in five solvents, H2O, D2O, CH3OH, CH3CN, and (CH3)2SO, relaxation rates followed
      the trend of OCN- > SCN- > SeCN-. For these anions and isotopes of SCN-, the
      relaxation rate was a factor of a few (2.5-10) higher in H2O than in D2O. To
      further probe the solvent isotope effect, the relaxation rates of S12C14N-,
      S13C14N-, and S12C15N- in deuterated methanols (CH3OH, CH3OD, CH3OH, CD3OD) were
      compared. Relaxation rate was found to be affected by the change of solvent
      vibrational band at the CN- stretching mode (CD3 symmetric stretch) and lower
      frequency regions, suggesting the presence of both direct IET and solvent
      assisted IVR relaxation pathways. The possible relaxation pathways and mechanisms
      for the observed trends in solute and solvent dependence were discussed.

PMID- 17020388
TI  - Ultrafast two-dimensional infrared vibrational echo chemical exchange experiments
      and theory.
AB  - Ultrafast two-dimensional (2D) infrared vibrational echo experiments and theory
      are used to examine chemical exchange between solute-solvent complexes and the
      free solute for the solute phenol and three solvent complex partners, p-xylene,
      benzene, and bromobenzene, in mixed solvents of the partner and CCl4. The
      experiments measure the time evolution of the 2D spectra of the hydroxyl (OD)
      stretching mode of the phenol. The time-dependent 2D spectra are analyzed using
      time-dependent diagrammatic perturbation theory with a model that includes the
      chemical exchange (formation and dissociation of the complexes), spectral
      diffusion of both the complex and the free phenol, orientational relaxation of
      the complexes and free phenol, and the vibrational lifetimes. The detailed
      calculations are able to reproduce the experimental results and demonstrate that
      a method employed previously that used a kinetic model for the volumes of the
      peaks is adequate to extract the exchange kinetics. The current analysis also
      yields the spectral diffusion (time evolution of the dynamic line widths) and
      shows that the spectral diffusion is significantly different for phenol complexes
      and free phenol.

PMID- 17020389
TI  - Dynamics of surface catalyzed reactions; the roles of surface defects, surface
      diffusion, and hot electrons.
AB  - The mechanism that controls bond breaking at transition metal surfaces has been
      studied with sum frequency generation (SFG), scanning tunneling microscopy (STM),
      and catalytic nanodiodes operating under the high-pressure conditions. The
      combination of these techniques permits us to understand the role of surface
      defects, surface diffusion, and hot electrons in dynamics of surface catalyzed
      reactions. Sum frequency generation vibrational spectroscopy and kinetic
      measurements were performed under 1.5 Torr of cyclohexene
      hydrogenation/dehydrogenation in the presence and absence of H(2) and over the
      temperature range 300-500 K on the Pt(100) and Pt(111) surfaces. The structure
      specificity of the Pt(100) and Pt(111) surfaces is exhibited by the surface
      species present during reaction. On Pt(100), pi-allyl c-C6H9, cyclohexyl (C6H11),
      and 1,4-cyclohexadiene are identified adsorbates, while on the Pt(111) surface,
      pi-allyl c-C6H9, 1,4-cyclohexadiene, and 1,3-cyclohexadiene are present. A
      scanning tunneling microscope that can be operated at high pressures and
      temperatures was used to study the Pt(111) surface during the catalytic
      hydrogenation/dehydrogenation of cyclohexene and its poisoning with CO. It was
      found that catalytically active surfaces were always disordered, while ordered
      surface were always catalytically deactivated. Only in the case of the CO
      poisoning at 350 K was a surface with a mobile adsorbed monolayer not
      catalytically active. From these results, a CO-dominated mobile overlayer that
      prevents reactant adsorption was proposed. By using the catalytic nanodiode, we
      detected the continuous flow of hot electron currents that is induced by the
      exothermic catalytic reaction. During the platinum-catalyzed oxidation of carbon
      monoxide, we monitored the flow of hot electrons over several hours using a metal
      semiconductor Schottky diode composed of Pt and TiO2. The thickness of the Pt
      film used as the catalyst was 5 nm, less than the electron mean free path,
      resulting in the ballistic transport of hot electrons through the metal. The
      electron flow was detected as a chemicurrent if the excess electron kinetic
      energy generated by the exothermic reaction was larger than the effective
      Schottky barrier formed at the metal-semiconductor interface. The measurement of
      continuous chemicurrent indicated that chemical energy of exothermic catalytic
      reaction was directly converted into hot electron flux in the catalytic
      nanodiode. We found the chemicurrent was well-correlated with the turnover rate
      of CO oxidation separately measured by gas chromatography.

PMID- 17020390
TI  - Optical control of excited-state vibrational coherences of a molecule in
      solution: The influence of the excitation pulse spectrum and phase in LD690.
AB  - Spectral and phase shaping of femtosecond laser pulses is used to selectively
      excite vibrational wave packets on the ground (S0) and excited (S1) electronic
      states in the laser dye LD690. The transient absorption signals observed
      following excitation near the peak of the ground-state absorption spectrum are
      characterized by a dominant 586 cm(-1) vibrational mode. This vibration is
      assigned to a wave packet on the S0 potential energy surface. When the excitation
      pulse is tuned to the blue wing of the absorption spectrum, a lower frequency 568
      cm(-1) vibration dominates the response. This lower frequency mode is assigned to
      a vibrational wave packet on the S1 electronic state. The spectrum and phase of
      the excitation pulse also influence both the dephasing of the vibrational wave
      packet and the amplitude profiles of the oscillations as a function of probe
      wavelength. Excitation by blue-tuned, positively chirped pulses slows the
      apparent dephasing of the vibrational coherences compared with a transform
      limited pulse having the same spectrum. Blue-tuned negatively chirped excitation
      pulses suppress the observation of coherent oscillations in the ground state.

PMID- 17020391
TI  - Heterogeneous exciton dynamics revealed by two-dimensional optical spectroscopy.
AB  - We show that optical two-dimensional (2D) spectroscopy can recover ultrafast
      heterogeneous dynamics of closely spaced delocalized exciton states from a
      molecular exciton manifold characterized by a single absorption band. The
      complete experimental third-order nonlinear optical response from room
      temperature J-aggregates in liquid phase is reproduced for the first time with
      self-consistent Frenkel exciton theory combined with modified Redfield theory. We
      show that exciton relaxation between the exciton states and nuclear-motion
      induced exchange-narrowed energy fluctuations of individual delocalized exciton
      states can be distinguished because these two processes lead to a distinctively
      different evolution of the absolute 2D spectrum. Our technique also allows
      recovery of the variation of the exciton relaxation rates as well as the degree
      of exciton delocalization across the absorption band.

PMID- 17020392
TI  - Probing the local structure of liquid water by X-ray absorption spectroscopy.
AB  - It was recently suggested that liquid water primarily comprises hydrogen-bonded
      rings and chains, as opposed to the traditionally accepted locally tetrahedral
      structure (Wernet et al. Science 2004, 304, 995). This controversial conclusion
      was primarily based on comparison between experimental and calculated X-ray
      absorption spectra (XAS) using computer-generated ice-like 11-molecule clusters.
      Here we present calculations which conclusively show that when hydrogen-bonding
      configurations are chosen randomly, the calculated XAS does not reproduce the
      experimental XAS regardless of the bonding model employed (i.e., rings and chains
      vs tetrahedral). Furthermore, we also present an analysis of a recently
      introduced asymmetric water potential (Soper, A. K. J. Phys.: Condens. Matter
      2005, 17, S3273), which is representative of the rings and chains structure, and
      make comparisons with the standard SPC/E potential, which represents the locally
      tetrahedral structure. We find that the calculated XAS from both potentials is
      inconsistent with the experimental XAS. However, we also show the calculated
      electric field distribution from the rings and chains structure is strongly
      bimodal and highly inconsistent with the experimental Raman spectrum, thus
      casting serious doubt on the validity of the rings and chains model for liquid
      water.

PMID- 17020393
TI  - Molecular simulations of the pressure, temperature, and chemical potential
      dependencies of clay swelling.
AB  - A new method for the determination of clay swelling thermodynamics from computer
      simulation is discussed and evaluated. This method allows for the determination
      of temperature, pressure, and water chemical potential dependence of clay
      swelling from simulations at a single thermodynamic state point. The temperature
      dependence and pressure dependence of clay swelling are shown to be directly
      related to the composite system entropy and volume change, respectively, that
      accompany swelling. Expressions for the chemical potential dependence of clay
      swelling are used to determine constant pressure layer spacing and adsorption
      isotherms, quantities that are well suited for comparison with experimental
      measurements. This method is evaluated through grand isoshear ensemble
      simulations of Na-montmorillonite, a prototypical swelling clay. Approximations
      associated with all expressions are discussed with explicit calculations used to
      demonstrate their regimes of validity.

PMID- 17020394
TI  - Exploring the role of decoherence in condensed-phase nonadiabatic dynamics: a
      comparison of different mixed quantum/classical simulation algorithms for the
      excited hydrated electron.
AB  - Mixed quantum/classical (MQC) molecular dynamics simulation has become the method
      of choice for simulating the dynamics of quantum mechanical objects that interact
      with condensed-phase systems. There are many MQC algorithms available, however,
      and in cases where nonadiabatic coupling is important, different algorithms may
      lead to different results. Thus, it has been difficult to reach definitive
      conclusions about relaxation dynamics using nonadiabatic MQC methods because one
      is never certain whether any given algorithm includes enough of the necessary
      physics. In this paper, we explore the physics underlying different nonadiabatic
      MQC algorithms by comparing and contrasting the excited-state relaxation dynamics
      of the prototypical condensed-phase MQC system, the hydrated electron, calculated
      using different algorithms, including: fewest-switches surface hopping,
      stationary-phase surface hopping, and mean-field dynamics with surface hopping.
      We also describe in detail how a new nonadiabatic algorithm, mean-field dynamics
      with stochastic decoherence (MF-SD), is to be implemented for condensed-phase
      problems, and we apply MF-SD to the excited-state relaxation of the hydrated
      electron. Our discussion emphasizes the different ways quantum decoherence is
      treated in each algorithm and the resulting implications for hydrated-electron
      relaxation dynamics. We find that for three MQC methods that use Tully's fewest
      switches criterion to determine surface hopping probabilities, the excited-state
      lifetime of the electron is the same. Moreover, the nonequilibrium solvent
      response function of the excited hydrated electron is the same with all of the
      nonadiabatic MQC algorithms discussed here, so that all of the algorithms would
      produce similar agreement with experiment. Despite the identical solvent response
      predicted by each MQC algorithm, we find that MF-SD allows much more mixing of
      multiple basis states into the quantum wave function than do other methods. This
      leads to an excited-state lifetime that is longer with MF-SD than with any method
      that incorporates nonadiabatic effects with the fewest-switches surface hopping
      criterion.

PMID- 17020396
TI  - Antihypertensive medication is associated with less cognitive impairment in the
      very old with apolipoprotein-E epsilon4 allele.
AB  - BACKGROUND AND OBJECTIVES: High and low blood pressure and apolipoprotein (Apo)-E
      epsilon4 alleles have been shown to be associated with dementia of the
      Alzheimer's type. The aim of this study was to examine the relationship between
      Apo-E epsilon4 allele status and the effect of antihypertensive treatment on
      cognitive performance in persons > or =80 years of age. METHODS: A sample of 258
      individuals 80-102 years of age was studied. Associations between the Mini-Mental
      State Examination (MMSE) score and treatment with antihypertensive medication,
      blood pressure, Apo-E polymorphism, sex, age and education were assessed.
      Patients treated with antihypertensive drugs typically used two to ten different
      medications. RESULTS: Individuals with no Apo-E epsilon4 alleles who were not
      treated with antihypertensive medications had a significantly higher diastolic
      blood pressure than other participants in the study but no cognitive deficits.
      Participants who had at least one Apo-E epsilon4 allele who were not treated with
      antihypertensive medications scored significantly lower on the MMSE compared with
      other participants in the study. CONCLUSIONS: Individuals with an Apo-E epsilon4
      allele who were not treated with antihypertensive medication showed the poorest
      cognitive performance. This could suggest that individuals with the Apo-E
      epsilon4 allele may benefit cognitively from treatment with antihypertensive
      drugs.

PMID- 17020395
TI  - A review of the health-related quality of life and economic impact of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a chronic, neurodegenerative disease that places a
      substantial burden on patients, their families and carers, as well as on society
      as a whole. PD can severely affect the health-related quality of life (HR-QOL) of
      both patients and their carers and, as the disease progresses, HR-QOL
      deteriorates. This review aims to critically evaluate the literature on a number
      of important aspects that influence HR-QOL in relation to PD. Factors associated
      with a negative impact and ways to improve HR-QOL are highlighted, and tools for
      HR-QOL assessment reviewed. The economic impact of PD and related cost
      effectiveness studies are also reviewed. Over the course of the disease, patients
      with PD experience changes in their HR-QOL that are affected by factors such as
      depression, motor complications, education and surgery. However, a lack of
      uniformity in the choice of HR-QOL tools used in studies makes comparison of
      results difficult. Research on motor fluctuations and dyskinesias has shown
      conflicting results, whereas it is clear from the available data that depression
      needs to be more clearly recognised and treated. Inequality in the numbers of men
      and women receiving surgery still needs to be addressed and, again, in this area
      there is a lack of uniformity with respect to assessment for surgery. Education
      programmes have been shown to be successful in improving HR-QOL, although more
      research is needed about how to introduce such programmes to all PD patients. In
      particular, there has been little detailed research into young-onset PD and
      juvenile patients to assess the true impact of the disease on their HR-QOL. The
      literature has also shown that PD can affect the HR-QOL of the carer, which may
      have a 'knock-on' effect for the patient. The HR-QOL of carers needs more
      attention because these individuals can significantly reduce the burden that
      would otherwise fall on the health services in terms of cost and care. Research
      shows that the economic costs of PD are high, particularly for patients in
      advanced stages of the disease and those with motor complications. Although carer
      burden is a major source of costs, this is not factored into cost-effectiveness
      analyses. Furthermore, because too few studies use quality-adjusted life years as
      their health outcome, particularly in studies of the costs of surgery, comparison
      of costs of treatments is difficult. The review highlights the need for HR-QOL
      tools such as the EuroQol-5D to be used together with disease-specific tools to
      provide the most comprehensive picture of the costs and impact of PD.A recent
      upsurge in published literature on PD resulting from increased interest in HR-QOL
      issues has led to an at times overwhelming amount of new information. The present
      review assembles the most important points relating to HR-QOL in PD raised in the
      literature, adds value to previously covered issues, and examines areas of HR-QOL
      in PD that have not previously been reviewed, such as education, carer burden and
      surgery, highlighting where more research is warranted.

PMID- 17020397
TI  - Drug costs associated with non-adherence to cholesterol management guidelines for
      primary prevention of cardiovascular disease in an elderly population: the
      Rotterdam study.
AB  - BACKGROUND: In The Netherlands, costs of HMG-CoA reductase inhibitor (statin) use
      have recently increased sharply compared with costs of other drugs. However,
      several studies have established both undertreatment and non-guidelines-indicated
      treatment with statins, suggesting a suboptimal use of resources. OBJECTIVE: To
      estimate the drug costs associated with non-guidelines-indicated treatment and
      undertreatment with statins in an elderly population. PATIENTS AND SETTING: Data
      were obtained from the Rotterdam Study, a population-based prospective cohort
      study which began in 1990 with 7983 participants aged > or =55 years. Subjects
      with a history of cardiovascular disease (CVD) were excluded. Pharmacy records
      were used to assess patterns of medication use in daily medical practice. MAIN
      OUTCOME MEASURE: Non-guidelines-indicated treatment and undertreatment with
      statins were established in relation to Dutch cholesterol management guidelines
      for all participants. We calculated the costs of statin therapy associated with
      non-guidelines-indicated treatment, and the costs of statins if all those
      undertreated were to receive statins. The results were projected on to the Dutch
      population to determine the economic implications of non-adherence to cholesterol
      management guidelines in the elderly. RESULTS: Of the participants who started
      treatment with statins for the primary prevention of CVD during follow-up, 69%
      received non-guidelines-indicated treatment. More men (7.5%) were undertreated
      than women (1.6%) and more women (6.2%) received non-guidelines-indicated
      treatment than men (1.5%). Among the participants without CVD who were still
      alive at 1 January 2002, 14% were eligible for statin therapy but were untreated.
      After projection of the prevalence of non-guidelines-indicated treatment and
      undertreatment to the Dutch population, the absolute costs for non-guidelines
      indicated treatment with statins in 2005 were estimated to be approximately 23
      million euro(uncertainty limits [UL]: 19-28 million euro), while the cost to
      eliminate undertreatment was also 23 million euro (UL: 19-28 million euro).
      CONCLUSION: Reallocation of resources used for statin therapy from those
      receiving non-guidelines-indicated treatment to those being undertreated could
      lead to a more efficient use of resources.

PMID- 17020398
TI  - Inappropriate medication use in elderly lebanese outpatients: prevalence and risk
      factors.
AB  - BACKGROUND: Inappropriate use of medications has become an international cause
      for concern in geriatric patients, who are at high risk of drug-related
      morbidity. This study is the first attempt to determine the prevalence of
      inappropriate drug use in elderly Lebanese outpatients, using community pharmacy
      data, and to identify factors that predict potentially inappropriate drug intake
      in this population. METHODS: Records of elderly patients aged > or =65 years were
      selected from different community pharmacies. Each patient profile was reviewed
      and to confirm patient record information, in-person interviews were conducted
      with elderly patients between November 2004 and May 2005 by qualified
      pharmacists. Based on a literature review describing guidelines for the
      inappropriate use of medications in the elderly, courses of therapy were assessed
      and classified as either appropriate or inappropriate. Courses of therapy that
      were judged inappropriate were further classified according to the specific area
      of inappropriate use (i.e. Beers' criteria, duplicate therapy, indication, dose,
      dose frequency including missing doses, duration and discontinuation of therapy,
      adverse effects, drug-drug and/or drug-disease interactions, and poor memory).
      Statistical analyses were performed to estimate the prevalence of inappropriate
      medication use and to identify potentially predictive factors of such use arising
      from patients' sociodemographic characteristics, health factors and drug regimen
      intake. RESULTS: A total of 350 elderly patient profiles were reviewed, from
      which 277 evaluable records were obtained. More than half (59.6%) of the patients
      taking drugs at the time of the study were taking at least one inappropriate
      medication. Inappropriate medication use was most frequently identified in terms
      of Beers' criteria (22.4%), missing doses (18.8%) or incorrect frequency of
      administration of drugs (13.0%). Factors predicting potentially inappropriate
      drug intake included female sex (65.7% vs 53.3% for males, p = 0.03) and alcohol
      intake (p = 0.007). There were also significant associations between the
      likelihood of use of an inappropriate drug and (i) increased number of medical
      illnesses (p < 0.00002); and (ii) consumption of an over-the-counter drug (OTC)
      and/or prescription drug (p = 0.048 and p = 0.0035, respectively). The likelihood
      of use of an inappropriate drug was higher again when patients concurrently used
      both OTC and prescription drugs (p < 0.0002). CONCLUSION: The present study is
      the first to describe and assess inappropriate medication use by elderly
      outpatients in the Lebanese community setting. With increasing availability of
      newer and more appropriate medications, use of potentially inappropriate drugs
      may decrease. Pharmacists have a major role to play in counselling patients about
      the importance of appropriate drug use.

PMID- 17020399
TI  - Topical brimonidine 0.2%/timolol 0.5% ophthalmic solution: in glaucoma and ocular
      hypertension.
AB  - A fixed combination of brimonidine (a highly selective alpha(2)-adrenergic
      agonist) and timolol (a non-selective beta-blocker) [brimonidine 0.2%/timolol
      0.5% ophthalmic solution; brimonidine/timolol] is available for the topical
      treatment of glaucoma and ocular hypertension (OH). Brimonidine and timolol
      decrease elevated intraocular pressure (IOP) by complementary mechanisms of
      action and have an additive effect when coadministered to healthy volunteers and
      patients with glaucoma or OH. When assessed over a 3- or 12-month period in
      large, well designed clinical studies, brimonidine/timolol instilled twice daily
      (one drop in each eye) was superior to monotherapy with the individual components
      instilled two (brimonidine) or three (timolol) times daily, and noninferior to
      concomitant therapy with the individual components instilled twice daily, in
      lowering raised IOP in patients with glaucoma or OH. In small, randomised,
      comparative studies of 1 or 3 months' duration, the IOP-lowering effect of
      brimonidine/timolol twice daily was similar or superior to that of fixed
      combination dorzolamide 2%/timolol 0.5% ophthalmic solution (dorzolamide/timolol)
      twice daily (preliminary data). Brimonidine/timolol is generally well tolerated
      with a predictable local and systemic adverse event profile based on that of the
      individual components used alone and concomitantly. No unexpected or serious
      adverse events associated with the fixed combination were reported in key
      clinical trials. Brimonidine/timolol may be advantageous over dorzolamide/timolol
      with respect to ocular tolerability and comfort (preliminary data).

PMID- 17020400
TI  - Brimonidine/Timolol: a viewpoint by Richard Fiscella.

PMID- 17020401
TI  - Brimonidine/Timolol: a viewpoint by Robert M. Feldman.

PMID- 17020402
TI  - Brimonidine/Timolol: a viewpoint by Francisco J. Goni.

PMID- 17020404
TI  - Combining information from common type 2 diabetes risk polymorphisms improves
      disease prediction.
AB  - BACKGROUND: A limited number of studies have assessed the risk of common diseases
      when combining information from several predisposing polymorphisms. In most
      cases, individual polymorphisms only moderately increase risk (approximately
      20%), and they are thought to be unhelpful in assessing individuals' risk
      clinically. The value of analyzing multiple alleles simultaneously is not well
      studied. This is often because, for any given disease, very few common risk
      alleles have been confirmed. METHODS AND FINDINGS: Three common variants (Lys23
      of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been
      shown to predispose to type 2 diabetes mellitus across many large studies. Risk
      allele frequencies ranged from 0.30 to 0.88 in controls. To assess the combined
      effect of multiple susceptibility alleles, we genotyped these variants in a large
      case-control study (3,668 controls versus 2,409 cases). Individual allele odds
      ratios (ORs) ranged from 1.14 (95% confidence interval [CI], 1.05 to 1.23) to
      1.48 (95% CI, 1.36 to 1.60). We found no evidence of gene-gene interaction, and
      the risks of multiple alleles were consistent with a multiplicative model. Each
      additional risk allele increased the odds of type 2 diabetes by 1.28 (95% CI,
      1.21 to 1.35) times. Participants with all six risk alleles had an OR of 5.71
      (95% CI, 1.15 to 28.3) compared to those with no risk alleles. The 8.1% of
      participants that were double-homozygous for the risk alleles at TCF7L2 and
      Pro12Ala had an OR of 3.16 (95% CI, 2.22 to 4.50), compared to 4.3% with no
      TCF7L2 risk alleles and either no or one Glu23Lys or Pro12Ala risk alleles.
      CONCLUSIONS: Combining information from several known common risk polymorphisms
      allows the identification of population subgroups with markedly differing risks
      of developing type 2 diabetes compared to those obtained using single
      polymorphisms. This approach may have a role in future preventative measures for
      common, polygenic diseases.

PMID- 17020405
TI  - Tuberculosis recurrence and mortality after successful treatment: impact of drug
      resistance.
AB  - BACKGROUND: The DOTS (directly observed treatment short-course) strategy for
      tuberculosis (TB) control is recommended by the World Health Organization
      globally. However, there are few studies of long-term TB treatment outcomes from
      DOTS programs in high-burden settings and particularly settings of high drug
      resistance. A DOTS program was implemented progressively in Karakalpakstan,
      Uzbekistan starting in 1998. The total case notification rate in 2003 was
      462/100,000, and a drug resistance survey found multidrug-resistant (MDR)
      Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated
      patients. A retrospective, observational study was conducted to assess the
      capacity of standardized short-course chemotherapy to effectively cure patients
      with TB in this setting. METHODS AND FINDINGS: Using routine data sources, 213
      patients who were sputum smear-positive for TB, included in the drug resistance
      survey and diagnosed consecutively in 2001-2002 from four districts, were
      followed up to a median of 22 months from diagnosis, to determine mortality and
      subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of
      these patients. Mortality was high, with an average of 15% (95% confidence
      interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible
      cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99
      new cases were "successfully" treated, 25 (34%) of these patients were
      subsequently rediagnosed with recurrent TB (13 were smear-positive on
      rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to
      six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection
      and previous TB treatment predicted unsuccessful DOTS treatment, while initial
      drug resistance contributed substantially to both mortality and disease
      recurrence after successful DOTS treatment. CONCLUSIONS: These results suggest
      that specific treatment of drug-resistant TB is needed in similar settings of
      high drug resistance. High disease recurrence after successful treatment, even
      for drug-susceptible cases, suggests that at least in this setting, end-of
      treatment outcomes may not reflect the longer-term status of patients, with
      consequent negative impacts for patients and for TB control.

PMID- 17020406
TI  - A comparative analysis of influenza vaccination programs.
AB  - BACKGROUND: The threat of avian influenza and the 2004-2005 influenza vaccine
      supply shortage in the United States have sparked a debate about optimal
      vaccination strategies to reduce the burden of morbidity and mortality caused by
      the influenza virus. METHODS AND FINDINGS: We present a comparative analysis of
      two classes of suggested vaccination strategies: mortality-based strategies that
      target high-risk populations and morbidity-based strategies that target high
      prevalence populations. Applying the methods of contact network epidemiology to a
      model of disease transmission in a large urban population, we assume that vaccine
      supplies are limited and then evaluate the efficacy of these strategies across a
      wide range of viral transmission rates and for two different age-specific
      mortality distributions. We find that the optimal strategy depends critically on
      the viral transmission level (reproductive rate) of the virus: morbidity-based
      strategies outperform mortality-based strategies for moderately transmissible
      strains, while the reverse is true for highly transmissible strains. These
      results hold for a range of mortality rates reported for prior influenza
      epidemics and pandemics. Furthermore, we show that vaccination delays and
      multiple introductions of disease into the community have a more detrimental
      impact on morbidity-based strategies than mortality-based strategies.
      CONCLUSIONS: If public health officials have reasonable estimates of the viral
      transmission rate and the frequency of new introductions into the community prior
      to an outbreak, then these methods can guide the design of optimal vaccination
      priorities. When such information is unreliable or not available, as is often the
      case, this study recommends mortality-based vaccination priorities.

PMID- 17020407
TI  - Antidepressant prevention of postnatal depression.

PMID- 17020409
TI  - Five myths about the HIV epidemic in Asia.

PMID- 17020408
TI  - Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer.
AB  - BACKGROUND: Nuclear factor erythroid-2 related factor 2 (NRF2) is a redox
      sensitive transcription factor that positively regulates the expression of genes
      encoding antioxidants, xenobiotic detoxification enzymes, and drug efflux pumps,
      and confers cytoprotection against oxidative stress and xenobiotics in normal
      cells. Kelch-like ECH-associated protein 1 (KEAP1) negatively regulates NRF2
      activity by targeting it to proteasomal degradation. Increased expression of
      cellular antioxidants and xenobiotic detoxification enzymes has been implicated
      in resistance of tumor cells against chemotherapeutic drugs. METHODS AND
      FINDINGS: Here we report a systematic analysis of the KEAP1 genomic locus in lung
      cancer patients and cell lines that revealed deletion, insertion, and missense
      mutations in functionally important domains of KEAP1 and a very high percentage
      of loss of heterozygosity at 19p13.2, suggesting that biallelic inactivation of
      KEAP1 in lung cancer is a common event. Sequencing of KEAP1 in 12 cell lines and
      54 non-small-cell lung cancer (NSCLC) samples revealed somatic mutations in KEAP1
      in a total of six cell lines and ten tumors at a frequency of 50% and 19%,
      respectively. All the mutations were within highly conserved amino acid residues
      located in the Kelch or intervening region domain of the KEAP1 protein,
      suggesting that these mutations would likely abolish KEAP1 repressor activity.
      Evaluation of loss of heterozygosity at 19p13.2 revealed allelic losses in 61% of
      the NSCLC cell lines and 41% of the tumor samples. Decreased KEAP1 activity in
      cancer cells induced greater nuclear accumulation of NRF2, causing enhanced
      transcriptional induction of antioxidants, xenobiotic metabolism enzymes, and
      drug efflux pumps. CONCLUSIONS: This is the first study to our knowledge to
      demonstrate that biallelic inactivation of KEAP1 is a frequent genetic alteration
      in NSCLC. Loss of KEAP1 function leading to constitutive activation of NRF2
      mediated gene expression in cancer suggests that tumor cells manipulate the NRF2
      pathway for their survival against chemotherapeutic agents.

PMID- 17020412
TI  - Hereditary spastic paraplegia: clinical genomics and pharmacogenetic
      perspectives.
AB  - Hereditary spastic paraplegias (HSPs) are a group of single-gene disorders
      characterised by degeneration of the corticospinal tract axons, leading to
      bilateral, symmetrical, slowly-progressive spastic paraparesis, predominantly of
      the lower extremities. So far, ~ 30 different chromosomal HSP loci have been
      identified by genetic linkage analysis. Defects in intracellular trafficking and
      transport in myelination and abnormalities of mitochondrial proteins have been
      involved in HSP pathogenesis. At present, treatment of the HSPs is primarily
      directed symptomatically toward reducing muscle spasticity. Yet, recent
      progresses in the identification of HSP mutations are providing formidable tools
      to pharmacogenetic approaches of drug discovery, validation and prediction of
      individual response.

PMID- 17020410
TI  - Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.
AB  - Although compound heterozygosity, or the presence of two different mutant alleles
      of the same gene, is common in human recessive disease, its potential to impact
      disease outcome has not been well documented. This is most likely because of the
      inherent difficulty in distinguishing specific biallelic effects from differences
      in environment or genetic background. We addressed the potential of different
      recessive alleles to contribute to the enigmatic pleiotropy associated with XPD
      recessive disorders in compound heterozygous mouse models. Alterations in this
      essential helicase, with functions in both DNA repair and basal transcription,
      result in diverse pathologies ranging from elevated UV sensitivity and cancer
      predisposition to accelerated segmental progeria. We report a variety of
      biallelic effects on organismal phenotype attributable to combinations of
      recessive Xpd alleles, including the following: (i) the ability of homozygous
      lethal Xpd alleles to ameliorate a variety of disease symptoms when their
      essential basal transcription function is supplied by a different disease-causing
      allele, (ii) differential developmental and tissue-specific functions of distinct
      Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely
      reported at clinically relevant loci in mammals. Our data suggest a re-evaluation
      of the contribution of "null" alleles to XPD disorders and highlight the
      potential of combinations of recessive alleles to affect both normal and
      pathological phenotypic plasticity in mammals.

PMID- 17020411
TI  - tRNAs promote nuclear import of HIV-1 intracellular reverse transcription
      complexes.
AB  - Infection of non-dividing cells is a biological property of HIV-1 crucial for
      virus transmission and AIDS pathogenesis. This property depends on nuclear import
      of the intracellular reverse transcription and pre-integration complexes
      (RTCs/PICs). To identify cellular factors involved in nuclear import of HIV-1
      RTCs, cytosolic extracts were fractionated by chromatography and import activity
      examined by the nuclear import assay. A near-homogeneous fraction was obtained,
      which was active in inducing nuclear import of purified and labeled RTCs. The
      active fraction contained tRNAs, mostly with defective 3' CCA ends. Such tRNAs
      promoted HIV-1 RTC nuclear import when synthesized in vitro. Active tRNAs were
      incorporated into and recovered from virus particles. Mutational analyses
      indicated that the anticodon loop mediated binding to the viral complex whereas
      the T-arm may interact with cellular factors involved in nuclear import. These
      tRNA species efficiently accumulated into the nucleus on their own in a energy-
      and temperature-dependent way. An HIV-1 mutant containing MLV gag did not
      incorporate tRNA species capable of inducing HIV-1 RTC nuclear import and failed
      to infect cell cycle-arrested cells. Here we provide evidence that at least some
      tRNA species can be imported into the nucleus of human cells and promote HIV-1
      nuclear import.

PMID- 17020413
TI  - Clinical application of pharmacogenetics in gastrointestinal diseases.
AB  - As knowledge of the human genome grows, there will be a direct impact on the
      management of specific diseases. Within gastroenterology and hepatology, there
      has been a change in the understanding of how variations or mutations in genes
      involved in drug metabolism or disease pathophysiology affect response to
      therapy. This review discusses the application of clinical pharmacogenetics to
      the following diseases and disorders: inflammatory bowel disease, Helicobacter
      pylori infections, gastroesophageal reflux disease, irritable bowel syndrome,
      functional dyspepsia, liver transplantation and colon cancer. Although only a few
      genotyping tests are regularly used in clinical practice, it is anticipated that
      studies will propel the routine use of many of the tests described in this
      review, in the future.

PMID- 17020414
TI  - Review of antipsychotics in children and adolescents.
AB  - The use of antipsychotics in children and adolescents in the clinical setting is
      increasing. This article reviews 77 clinical trials published in the last 10
      years, investigating their efficacy, effectiveness, safety and pharmacokinetic
      data in paediatric populations. The diagnostic categories in which the
      antipsychotics are commonly used (schizophrenia, pervasive developmental
      disorders, Tourette's disorder, mental retardation/subaverage intelligence, mood
      disorders and disruptive behaviour disorders) were used in order to review the
      evidence and effectiveness. All randomised, double-blind, placebo-controlled
      trials from the past decade are also summarised. This review refers to recent
      relevant practice parameters, guidelines and reviews throughout the text.
      Consistent with previous reviews, it is concluded that the recent trend of
      increased use of antipsychotics in children and adolescents is not adequately
      supported by evidence. Specific suggestions have been provided on how to
      incorporate the existing evidence base into clinical decision making. The review
      ends with the authors' opinion on the clinical and research implications for the
      field and future directions.

PMID- 17020415
TI  - Hyperoxaluria and systemic oxalosis: current therapy and future directions.
AB  - Excessive urinary oxalate excretion, termed hyperoxaluria, may arise from
      inherited or acquired diseases. The most severe forms are caused by increased
      endogenous production of oxalate related to one of several inborn errors of
      metabolism, termed primary hyperoxaluria. Recurrent kidney stones and progressive
      medullary nephrocalcinosis lead to the loss of kidney function, requiring
      dialysis or transplantation, accompanied by systemic oxalate deposition that is
      termed systemic oxalosis. For most primary hyperoxalurias, accurate diagnosis
      leads to the use of therapies that include pyridoxine supplementation, urinary
      crystallisation inhibitors, hydration with enteral fluids and, in the near
      future, probiotic supplementation or other innovative therapies. These therapies
      have varying degrees of success, and none represent a cure. Organ transplantation
      results in reduced patient and organ survival when compared with national
      statistics. Exciting new approaches under investigation include the restoration
      of defective enzymatic activity through the use of chemical chaperones and
      hepatocyte cell transplantation, or recombinant gene therapy for enzyme
      replacement. Such approaches give hope for a future therapeutic cure for primary
      hyperoxaluria that includes correction of the underlying genetic defect without
      exposure to the life-long dangers associated with organ transplantation.

PMID- 17020416
TI  - Emerging strategies for lowering serum phosphorous in patients with end-stage
      renal disease.
AB  - Hyperphosphataemia is a major problem in patients with chronic kidney disease as
      it has been associated with increased morbidity and mortality. Over the last four
      decades, different modalities have been applied to treat hyperphosphataemia with
      varying degrees of success. Unfortunately, treatment strategies have led to
      unforeseen complications. These have prompted the development of new classes of
      medications with potentially better efficacy and few short-term and long-term
      side effects. This article reviews the causes, mechanism and management of
      hyperphosphataemia.

PMID- 17020417
TI  - Update in the treatment of paediatric ulcerative colitis.
AB  - Ulcerative colitis is an important disease in the paediatric population.
      Ulcerative colitis is one of the chronic inflammatory bowel diseases, and is
      medically incurable. However, the arsenal of medications has grown as knowledge
      of the pathogenesis of this disease advances. This review looks at the classical
      treatments for children with ulcerative colitis, including the 5
      aminosalicylates, corticosteroids and imunomodulators, as well as biological
      therapy and other, newer modalities.

PMID- 17020418
TI  - Update on the use of aromatase inhibitors in breast cancer.
AB  - Estrogens are biosynthesised from androgens by the CYP450 enzyme complex called
      aromatase. Aromatase is expressed in the ovary, placenta, brain, bone, adipose
      tissue and breast tissue. In breast cancer, intratumoural aromatase is the source
      for local estrogen production in the tissue. Inhibition of aromatase is an
      important approach for reducing growth stimulatory effects of estrogens in
      estrogen-dependent breast cancer. The potent and selective third-generation
      aromatase inhibitors anastrozole, letrozole and exemestane were introduced to the
      market as endocrine therapy in postmenopausal patients failing anti-estrogen
      therapy alone, or multiple hormonal therapies. Anastrozole and letrozole are both
      non-steroidal aromatase inhibitors that compete with the substrate for binding to
      the enzyme active site. Exemestane is a mechanism-based steroidal inhibitor that
      mimics the substrate, is converted by the enzyme to a reactive intermediate, and
      results in inactivation of aromatase. These third-generation aromatase inhibitors
      are currently approved as first-line therapy for the treatment of postmenopausal
      women with metastatic estrogen-dependent breast cancer. The use of an aromatase
      inhibitor as initial therapy, or after treatment with tamoxifen, is now
      recommended as adjuvant hormonal therapy for postmenopausal women with hormone
      dependent breast cancer. Several clinical studies of aromatase inhibitors focus
      on the use of these agents in the adjuvant setting, for the treatment of early
      breast cancer. Recently published results show improved responses with these
      agents compared with tamoxifen.

PMID- 17020419
TI  - Economic evaluation of the prevention and management of systemic fungal
      infections in neutropenic patients.
AB  - Systemic fungal infections in neutropenic patients remain a clinical problem that
      is associated with morbidity and mortality. Continuing efforts are being made to
      develop improved (i.e., more effective or safe) drugs, and several new treatments
      have recently become available. These have increased the therapeutic options
      available to clinicians to address the problem of systemic fungal infections.
      Therapeutic choices are difficult when taking into account aspects of efficacy,
      safety and costs that are associated with the available alternatives. This review
      summarises the present status of health economic knowledge of the standard
      therapies that have been available for many years, and also reports on the most
      recent health economic evidence available for the newly developed treatment
      alternatives.

PMID- 17020420
TI  - Candesartan for the management of heart failure: more than an alternative.
AB  - Candesartan is a long-acting angiotensin receptor antagonist that is well
      absorbed from the gastrointestinal tract, with insurmountable receptor binding
      abilities. Recent studies have shown candesartan to be an effective therapy for
      heart failure patients, producing a significant reduction in mortality and
      morbidity. Importantly, studies have demonstrated that candesartan is effective
      in heart failure patients who are intolerant to angiotensin-converting enzyme
      inhibitors, in patients already receiving angiotensin-converting enzyme
      inhibitors and for heart failure patients with preserved systolic function. The
      primary end point in the latter group failed to achieve statistical significance
      due to the small number of events. This paper will review the data supporting the
      use of candesartan to treat all heart failure patients, regardless of their
      ejection fraction.

PMID- 17020421
TI  - Nadifloxacin: a quinolone for topical treatment of skin infections and potential
      for systemic use of its active isomer, WCK 771.
AB  - Nadifloxacin is a potent, broad-spectrum, quinolone agent approved for topical
      use in acne vulgaris and skin infections in Japan. As exposure of pathogenic and
      colonising bacteria to antibiotics results in drug resistance, it is not
      desirable to use an important, broad-spectrum antibiotic, which belongs to a
      class of agents widely used systemically to treat a wide variety of infections,
      as a topically applied preparation. On this basis, nadifloxacin is not a good
      option for topical treatment of acne when other effective non-antibiotic
      treatments are available. Nadifloxacin has potential as a topical agent for short
      term treatment of skin infections. The arginine salt of its (-)-(S)-isomer is
      being developed as a parenteral agent based on its potency against methicillin
      and quinolone-resistant Staphylococcus aureus.

PMID- 17020422
TI  - Topical pimecrolimus for skin disease other than atopic dermatitis.
AB  - Pimecrolimus is an ascomycin macrolactam. It is a specific calcineurin inhibitor
      that allows topical application. The highly lipophilic nature of this compound
      reduces the risk of systemic absorption through normal and inflammed skin.
      Pimecrolimus shows activity not only against T-cell activation, but also against
      mast cells and pruritus. Pimecrolimus 1% cream is approved for atopic dermatitis,
      and also has a great potential in other inflammatory skin diseases. Clinical
      trials have been performed in contact- and seborrhoeic dermatitis, genital lichen
      sclerosus, intertriginous psoriasis and cutaneous lupus erythematosus. In other
      diseases, the available data are limited to small case series, or individual
      cases of graft-versus-host disease or Netherton's disease. Although the use of
      calcineurin inhibitors in the treatment of vitiligo is promising, detailed
      studies with pimecrolimus and ultraviolet-irradiation are necessary and there is
      a need for prospective randomised, double-blind controlled trials.

PMID- 17020423
TI  - Tiagabine in anxiety disorders.
AB  - GABA has been implicated in both the aetiology and treatment of anxiety.
      Tiagabine is currently the only selective GABA reuptake inhibitor available in US
      markets; it exerts its action via GAT-1 transporter blockade presynaptically,
      facilitating GABA neurotransmission. Preclinical studies and current human
      studies suggest tiagabine possesses anxiolytic properties. The anxiolytic
      properties of tiagabine have also been suggested in a number of case series, open
      label studies and placebo-controlled studies in patients with different anxiety
      disorders. Throughout these studies, tiagabine has been reasonably tolerated; the
      most commonly reported adverse events include dizziness, headache and nausea.
      Tiagabine may be a useful addition to currently available drugs for anxiety;
      however, the data from small open-label investigations remain to be confirmed in
      larger controlled studies.

PMID- 17020424
TI  - Rupatadine: pharmacological profile and its use in the treatment of allergic
      disorders.
AB  - Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with
      a strong antagonist activity towards both histamine H(1) receptors and platelet
      activating factor receptors. The use of rupatadine is indicated in adult and
      adolescent patients (> 12 years of age) suffering from intermittent and
      persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment
      of these diseases, rupatadine is at least as effective as ebastine, cetirizine,
      loratadine and desloratadine. A very good safety profile of rupatadine has been
      evidenced in various studies, including a long-term (1-year) safety study.
      Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine
      and lorazepam, but should not be administered concomitantly with known CYP3A4
      inhibitors.

PMID- 17020425
TI  - Recent evidence of sustained benefit with exenatide in Type 2 diabetes.
AB  - Exenatide has been shown to improve glycaemic control (over 30 weeks) in subjects
      with Type 2 diabetes. A recent extension study has shown that, in metformin
      treated subjects with Type 2 diabetes, exenatide remained beneficial at 82 weeks.
      For those subjects who completed the study, in addition to the 1% fall in
      glycosylated haemoglobin (HbA1c) at 30 weeks, there was another 0.2% fall in
      HbA1c by 82 weeks. The weight loss achieved was a mean of 3 kg after 30 weeks,
      and this increased to 5.3 kg after 82 weeks in the completer cohort. In another
      extension study, continued benefit with exenatide was shown in subjects treated
      with metformin and/or sulfonylureas. For those subjects who completed the study,
      in addition to the 0.9% fall in HbA(1c) at 30 weeks, there was another 0.2% fall
      in HbA(1c) by 82 weeks. The weight loss achieved was a mean of 1.6 kg after 30
      weeks, and this increased to 2.1 kg after 82 weeks in the completer cohort. The
      subjects taking exenatide with metformin had a greater weight loss (5.3 kg),
      compared with those treated with a sulfonylurea (3.9 kg) and those taking
      metformin and a sulfonylurea (4.1 kg). In conclusion, extension studies have
      confirmed that exenatide is an exciting new and useful medicine for Type 2
      diabetes.

PMID- 17020426
TI  - British Association for Psychopharmacology Summer Meeting: 23-26 July 2006,
      Oxford, United Kingdom.
AB  - The 2006 British Association for Psychopharmacology Summer Meeting was held in
      Oxford, UK. The British Association for Psychopharmacology is now one of the
      largest national psychopharmacology associations in the world with over 1000
      members, and 550 national and international delegates attended the summer
      meeting. This meeting provides an annual forum for scientists and clinical
      investigators from academia and the pharmaceutical industry to share information
      on many aspects of the psychopharmacology of psychiatric illness. In total, 292
      abstracts were accepted for presentation at the meeting. These were divided into
      57 oral and 235 poster presentations. Research areas covered all aspects of
      psychopharmacology from basic research to pharmaceutical development and clinical
      application. This report highlights selected presentations from the meeting,
      focusing on rapid tryptophan depletion, which is a dietary manipulation that is
      used to study central serotonin function and putative animal models of depression
      and schizophrenia.

PMID- 17020427
TI  - Disease-modifying drugs for multiple sclerosis: current and future aspects.
AB  - Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of
      the human CNS, affecting an estimated 2.5 million people in the world. Until the
      1990s, treatment was mainly symptomatic, but a new era began with the
      introduction of disease-modifying therapy that seems to alter the natural course
      of MS. Current drugs include three interferons (IFNs): IFN-beta1a (Avonex
      intramuscular; Biogen, Cambridge, USA; Rebif subcutaneous; Serono, Geneva,
      Switzerland), IFN-beta1b (Betaseron subcutaneous; Schering, Berlin, Germany) and
      glatiramer acetate (Copaxone subcutaneous; Teva, Petach Tikva, Israel). Ongoing
      research targeting a variety of mechanisms and processes means there is much
      promise for the future treatment of MS.

PMID- 17020428
TI  - The role of proton-pump inhibitor therapy in patients with gastroesophageal
      reflux disease and difficult-to-control asthma.
AB  - Difficult-to-control asthma is a frustratingly difficult condition to treat. Many
      factors contribute to this condition, including gastroesophageal reflux disease.
      Response to potent acid suppressive therapy with proton-pump inhibitors is less
      than universal or complete, and underlines the multifactorial nature of the
      disease. However, the authors of this paper feel strongly that, whereas
      gastroesophageal reflux disease can be reliably identified, patients with
      difficult-to-control asthma will experience an improvement in symptoms when
      treated with acid-suppressive therapy, while bearing in mind that other
      contributory factors may have to be eliminated at the same time.

PMID- 17020429
TI  - Cephalosporins for uncomplicated skin and skin structure infections in emerging
      community-acquired MRSA.
AB  - The treatment of community uncomplicated skin and skin structure infections
      (uSSSIs) mandates that treatment should be based on careful consideration of
      infection attributes and patient characteristics, particularly in this era of
      community-acquired MRSA as an emerging pathogen. However, as most uSSSIs in the
      community continue to be caused by methicillin-susceptible Staphylococcus aureus
      or streptococci, effective treatment against these key pathogens should aim to
      achieve prompt eradication, along with minimal risk of antimicrobial resistance.
      Cephalosporins are an effective broad-spectrum empirical treatment for uSSSIs,
      with considerable activity against methicillin-susceptible S. aureus. In
      addition, the use of antimicrobial agents in infective strains that may be
      resistant does not appear to be associated with adverse patient-reported
      outcomes, suggesting that cephalosporins may still be effective in treating
      community-acquired MRSA-associated SSSIs.

PMID- 17020430
TI  - Antiviral treatment of hepatitis C.
AB  - Therapy of hepatitis C virus (HCV) infection may prevent progression to
      cirrhosis, hepatocellular carcinoma and end-stage liver disease. The cornerstone
      of treatment has long been standard IFN-alpha, the use of which was associated
      with a sustained biochemical and viral response in only a small proportion of
      patients. More recently, the success of interferon-based regimens has
      substantially improved due to the combination with the guanosine analogue
      ribavirin and to the advent of pegylated interferon formulations. However, even
      the most up-to-date regimens fail to cure the infection in many cases and are
      limited by side effects and high costs. A better understanding of the HCV genomic
      organisation, the elucidation of the three-dimensional structures of virally
      encoded enzymes and the recent development of a HCV-replicon system in human
      hepatoma (Huh-7) cells have led to significant advances in the development of new
      antiviral compounds, many of which are under evaluation in clinical trials. The
      aim of this review is to trace a brief overview of the progress made by
      interferon-based treatments for hepatitis C since their introduction in the early
      1990s, and to highlight the results of recent clinical studies concerning new and
      emerging drugs.

PMID- 17020431
TI  - Management of sepsis in the critically ill patient: key aspects.
AB  - Severe sepsis is a major cause of morbidity and mortality in the critically ill
      patient. Management involves identification and treatment of the underlying
      causative infection, with antimicrobial agents and surgery where necessary,
      haemodynamic resuscitation with fluids and vasoactive agents, steroids (for
      septic shock) and immunomodulation with drotrecogin-alpha (activated), where not
      contraindicated. Every effort must be made to identify sepsis early so as to
      optimise the patient's chances of a good outcome.

PMID- 17020432
TI  - Economic evaluation of sustained sedation/analgesia in the intensive care unit.
AB  - Lorazepam, midazolam, propofol and opioids are the primary agents that are used
      for sustained sedation and analgesia of critically ill patients. The choice of
      agent depends on safety profiles, expected outcomes, cost, patient
      characteristics and clinical experience. Few studies have comparatively evaluated
      the sedatives in terms of cost. Many factors, aside from drug costs, influence
      the total cost of sedation in the intensive care unit. This article reviews the
      cost parameters of intensive care unit sedation that are specific to the
      characteristics of commonly used sedatives and analgesics, evaluates economic
      studies and cost models, summarises alternative methods of sedation and
      analgesia, and provides practical recommendations for methods of cost
      containment, including daily sedation interruption, sedation monitoring and
      protocol implementation.

PMID- 17020433
TI  - Breast cancer expression profiling: the impact of microarray testing on clinical
      decision making.
AB  - The available clinical prognostic tools show an obvious limitation in predicting
      the outcome of breast cancer patients, and pathological features cannot classify
      tumours accurately. Microarray-based molecular classification of breast tumours
      or selection of gene expression panels to improve risk prediction or treatment
      outcomes are thought to be theoretically superior to established clinical and
      pathological criteria, based on guidelines such as the St Gallen and National
      Institute of Health consensus, or which use specific prognostic tools, such as
      the Nottingham Prognostic Index or Adjuvant-Online algorithm. Although two
      diagnostic tests based on gene expression profiling of breast cancer are
      commercially available, a new molecular classification and molecular forecasting
      of breast cancer based on expression profiling cannot outperform the standard
      tumour diagnostic at present. This review focuses on some important problems in
      the practical application of molecular profiling of breast cancer for clinical
      purposes.

PMID- 17020434
TI  - Optimising stroke prevention in non-valvular atrial fibrillation.
AB  - Atrial fibrillation is associated with substantial morbidity and mortality.
      Pooled data from trials comparing antithrombotic treatment with placebo have
      shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone
      reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to
      aspirin in preventing strokes, with a relative risk reduction of 36%.
      Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as
      vitamin K antagonist drugs in the prevention of embolic events, but has been
      recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial
      Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events)
      study has demonstrated that warfarin is superior to platelet therapy (clopidogrel
      plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa
      inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin
      converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold
      promise in atrial fibrillation through cardiac remodelling. Preliminary studies
      suggest that statins could interfere with the risk of recurrence after electrical
      cardioversion. Finally, percutaneous methods for the exclusion of left atrial
      appendage are under investigation in high-risk patients.

PMID- 17020435
TI  - Management of Type 2 diabetes: the role of incretin mimetics.
AB  - Type 2 diabetes is characterised by insulin resistance and progressive beta-cell
      dysfunction (which leads to hyperglycaemia), the risk of progressive worsening of
      glycaemic control and an increased risk of both macrovascular and microvascular
      complications. Existing treatment strategies target deficient insulin secretion
      and insulin resistance, but do not generally address the underlying progressive
      beta-cell dysfunction that is common to Type 2 diabetes. Traditionally, Type 2
      diabetes is first treated with medical nutrition therapy (reduced food intake and
      increased physical activity), followed by stepwise addition of oral antidiabetes
      therapies and, ultimately, exogenous insulin, as required. Unfortunately, these
      approaches have not been shown to delay the need for additional therapies, nor do
      they generally prevent or delay the inexorable decline in beta-cell function.
      Patients with Type 2 diabetes commonly experience deterioration in glycaemic
      control, and may have substantial weight gain due to the diabetes therapies that
      contribute to worsening obesity. In addition, insulin-providing therapies, such
      as sulfonylureas and exogenous insulin, carry the risk of hypoglycaemia, and
      cannot fully address the complex hormonal irregularities that characterise Type 2
      diabetes, including the role of glucagon hypersecretion. New therapeutic
      approaches are being developed that couple durable glycaemic control with
      improved control of body weight. These approaches include development of the
      incretin mimetics, which are a novel class of agents that share several of the
      glucoregulatory effects of incretin hormones, such as glucagon-like hormone-1.
      Deficiency of glucagon-like hormone-1 secretion is known to be present in those
      with abnormal glucose tolerance. Agents that manipulate the physiological actions
      of incretin hormones, such as glucagon-like hormone-1, may significantly benefit
      patients with Type 2 diabetes.

PMID- 17020436
TI  - The newly developed inhaled corticosteroid ciclesonide for the treatment of
      asthma.
AB  - Ciclesonide is the most recently developed inhaled corticosteroid for the
      treatment of asthma to enter global markets. It has been formulated as an aerosol
      solution in a metered dose inhaler with hydrofluoralkane. The mass median
      aerodynamic diameter of aerosolised ciclesonide is 1 - 2 microm, providing
      excellent lung deposition characteristics. Ciclesonide can undergo reversible
      esterification in the lungs, possibly allowing once-daily dosing, and is highly
      protein bound, possibly leading to reduced systemic side effects. Clinical trials
      suggest that ciclesonide effectively controls asthma and has a favourable safety
      profile.

PMID- 17020437
TI  - Osmotic, controlled-release methylphenidate for the treatment of ADHD.
AB  - Methylphenidate (MPH) is the most commonly used and best-studied stimulant
      medication for attention-deficit hyperactivity disorder. However, its short
      duration of action usually results in a requirement to administer multiple daily
      doses in order to achieve optimal clinical benefit. Although a wax-matrix-based
      SR formulation of MPH has been available since the 1990s, it was not well
      accepted into clinical practice. The variable absorption profile and lack of an
      immediate-release component results in a slower onset of action compared with
      immediate-release MPH. Hence, there was a need to develop alternative longer
      lasting preparations of MPH that were as efficacious as IR MPH, but which also
      addressed the problems inherent in multiple daily dosing. An osmotic, controlled
      release (OROS) formulation of MPH HCl has been developed over the past 10 years
      for once-daily administration. OROS MPH has been widely accepted by clinicians
      and is now the most widely prescribed MPH product in North America. Clinical
      trials have shown OROS MPH to have a continued action over a 12-h period, to be
      superior to placebo and to be as effective as immediate-release MPH dosed three
      times daily, in reducing symptoms of attention-deficit hyperactivity disorder,
      with similar incidence of side effects. There have been a smaller number of
      trials comparing OROS MPH with non-stimulant treatments, such as atomoxetine.

PMID- 17020438
TI  - Pregabalin for the treatment of generalised anxiety disorder.
AB  - Pregabalin is a new anxiolytic that has been recently licensed for the treatment
      of generalised anxiety disorder (GAD) in Europe. Short-term efficacy is based on
      six positive placebo-controlled studies, all of which showed a significant early
      separation from placebo in all of the doses used (150-600 mg) at the first week,
      and the efficacy at the end of the treatment was comparable with the comparators
      used in four of these studies. Pregabalin was effective in more or less severe
      GAD, on psychic and somatic symptoms of GAD, and in treating the subsyndromal
      depressive symptoms of GAD. Efficacy in the elderly was shown in a separate
      placebo-controlled study. The effect on cognitive function was minimal and
      notably less than that observed with benzodiazepines. The discontinuation
      symptoms following abrupt treatment cessation were similar to the rates with
      serotonin-noradrenaline re-uptake inhibitors and lower than with benzodiazepines
      with no signals of tolerance or dependence.

PMID- 17020439
TI  - Cetrorelix in the treatment of female infertility and endometriosis.
AB  - The use of cetrorelix within ovarian-stimulation protocols demonstrates several
      advantages compared with gonadotropin-releasing hormone (GnRH) agonist-containing
      protocols, which include, for example, significantly less time for analogue
      treatment and a reduction in the amount of gonadotropins needed. Furthermore,
      fewer side effects can be expected. There is no difference regarding endometrium
      quality and hormone profiles, and the results of assisted reproduction cycles are
      comparable. Cetrorelix also seems to be useful in the treatment of endometriosis
      which, in most cases, is an estrogen-dependent disease. Furthermore, fewer side
      effects occur with this agent (e.g., postmenopausal symptoms) and no estradiol
      add-back is needed. In the future, new nonpeptic GnRH antagonists are expected to
      be available for oral administration. Although they are still under
      investigation, these agents have the potential to improve patients' comfort and
      compliance.

PMID- 17020440
TI  - Which treatment for alcohol dependence: naltrexone, acamprosate and/or
      behavioural intervention?
AB  - Alcoholism is the third leading cause of preventable mortality and morbidity in
      the US. In the COMBINE (Combined Pharmacotherapies and Behavioural Interventions)
      study, the co-primary end points were the percentage of days abstinent and the
      time to first heavy drinking day after 16 weeks, and 1 year. The biggest
      difference observed in COMBINE was that seen between combined behavioural
      intervention (CBI; percentage of abstinent days = 66.6%) and CBI and medical
      management with placebos (79.8%). This illustrated a major effect of the medical
      management of nine sessions and/or the placebo pills. Acamprosate had no effect
      alone or in combination with naltrexone. At 16 weeks with medical management,
      there were 75.1% of the patients who were abstinent for placebos, and this was
      improved by naltrexone, CBI, and naltrexone with CBI (80.6, 78.2 and 77.1%,
      respectively). There was a follow up after 1 year, which showed that, with
      medical management, the amount of those who were abstinent for placebos was
      61.4%, and this was improved by naltrexone, CBI, and naltrexone with CBI (66.2,
      66.6 and 67.3%, respectively), but this improvement no longer reached statistical
      significance. After 1 year, there was no difference between groups in the overall
      frequency of hospitalisation, emergency treatment for alcohol problems, use of
      medication for drinking or emotional problems and detoxification. Being part of a
      study for alcohol dependence is known to increase the percentage of abstinent
      days. In COMBINE, this percentage was high in the group having medical management
      and placebo pills, and naltrexone or additional behavioural therapy only had
      modest additional effects.

PMID- 17020448
TI  - Head and neck oncology: what the past decade has taught us.

PMID- 17020450
TI  - Role of fludarabine in hematological malignancies.
AB  - Fludarabine is a prodrug that is converted to the free nucleoside 9-beta-D
      arabinosyl-2-fluoroadenine (F-ara-A), which enters cells and accumulates mainly
      as the 5'-triphosphate, F-ara-ATP. F-ara-ATP has multiple mechanisms of action,
      which are mostly directed toward DNA. Collectively, these actions affect DNA
      synthesis, which is the major mechanism of F-ara-A-induced cytotoxicity.
      Secondarily, incorporation into RNA and inhibition of transcription has been
      shown in cell lines. As a single agent, fludarabine has been effective for
      indolent leukemia. Biochemical modulation strategies resulted in enhanced
      accumulation of cytarabine triphosphate and led to the use of fludarabine for the
      treatment of acute leukemia. The combination of fludarabine with DNA-damaging
      agents to inhibit DNA repair processes has been highly effective for indolent
      leukemia and lymphomas. Other strategies have incorporated fludarabine into
      preparative regimens for nonmyeloablative stem-cell transplantation.

PMID- 17020451
TI  - Sipuleucel-T (APC8015) for prostate cancer.
AB  - Sipuleucel-T (Provenge; APC8015; Dendreon Corp, WA, USA) is a novel
      immunotherapeutic cellular product, which includes autologous dendritic cells
      pulsed ex vivo with a recombinant fusion protein (PA2024) consisting of
      granulocyte macrophage colony-stimulating factor and prostatic acid phosphatase.
      Two Phase II trials in men with androgen-dependent biochemically relapsed
      prostate cancer have demonstrated a decrease in prostate-specific antigen and
      prolongation in prostate-specific antigen doubling time. In men with hormone
      refractory prostate cancer, clinical trials have demonstrated both biological
      activity and clinical response to sipuleucel-T. Data from two Phase III trials in
      men with asymptomatic, metastatic hormone-refractory prostate cancer demonstrated
      an improved median overall survival in men who received sipuleucel-T compared
      with placebo. Clinical trials are ongoing or are being developed to evaluate
      sipuleucel-T in various prostate cancer disease states and in combination with
      other treatment modalities.

PMID- 17020452
TI  - Capecitabine-docetaxel combination treatment.
AB  - Metastatic breast cancer develops in approximately 50% of women diagnosed with
      breast cancer. The optimal treatment for patients with metastatic breast cancer
      has yet to be defined, owing to the heterogeneity of this group and the available
      agents. Patients with metastatic breast cancer often receive single-agent
      treatment in sequence as it is unclear whether combination therapy with cytotoxic
      drugs offers an overall disease-free survival benefit and single agents may offer
      less toxicity. The advantages of combination cytotoxic therapies have included
      higher response rates. However, such trials have not stratified on rapidity of
      disease progression or on tumor bulk. In previous studies, docetaxel is one of
      the few cytotoxic agents to demonstrate a survival benefit in anthracycline
      resistant patients and thus it has become a vital component of cytotoxic therapy.
      Capecitabine is also an important oral drug and has demonstrated activity in
      patients pretreated with anthracyclines and taxanes. Recent preclinical and
      clinical trials of this combination have demonstrated an increased time to tumor
      progression and overall survival benefit. Paclitaxel combined with gemcitabine
      has been compared with docetaxel plus capecitabine, with similar response rates
      and survival benefits. As patients on these trials have not received uniform
      crossover to the other active agent, whether or not the combination therapy
      offers an advantage for the entire cohort of metastatic patients or may be
      indicated for specific subgroups remains uncertain. Combination treatments may be
      preferable to sequential therapy for patients requiring urgent reduction in their
      tumor burden. Combinations of cytotoxic agents in combination with biological
      agents are currently being defined.

PMID- 17020453
TI  - Targeting epidermal growth factor receptor signaling in the treatment of head and
      neck cancer.
AB  - In this review, key aspects of epidermal growth factor receptor (EGFR) biology
      and the fruitful translation of these fundamental findings into recent treatment
      advances in head and neck squamous cell cancer (HNSCC) are highlighted. In
      contrast to a number of contemporary reviews of the EGFR, many of which focus on
      colorectal and nonsmall cell lung cancer, this review discusses the EGFR as a
      validated therapeutic target in HNSCC. Recent data confirm a survival advantage
      for the addition of the anti-EGFR monoclonal antibody cetuximab to definitive
      radiation therapy in locoregionally advanced HNSCC patients, as well as
      palliative benefits for patients with incurable recurrent and metastatic HNSCC.
      Small-molecule EGFR tyrosine kinase inhibitors also show considerable promise in
      this disease, both alone and in combination with radiation and chemotherapy. Both
      classes of anti-EGFR agent are generally well tolerated, with side effects
      (notably skin rash) that are distinct from the toxicities of conventional
      chemotherapy. Ongoing clinical trials will more clearly define the role for EGFR
      inhibitors in all treatment phases of HNSCC.

PMID- 17020454
TI  - Role of cytokines in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma is one of the most frequent cancers and
      standard treatment has only marginally improved the 5-year survival rate of
      patients with this disease in the last few decades. It is supposed that cytokine
      alterations in immune, inflammatory and angiogenetic regulatory routes within the
      head and neck squamous cell carcinoma microenvironment play a critical role in
      tumor aggressiveness, its response to chemo- and radiation therapies, as well as
      the development of immune escape mechanisms.

PMID- 17020455
TI  - Induction chemotherapy in the management of squamous cell carcinoma of the head
      and neck.
AB  - Platinum-based chemotherapy administered concurrently with radiation has been
      adopted as the standard treatment for locally advanced head and neck squamous
      cell carcinoma. Historically, randomized trials using induction chemotherapy
      prior to radiation therapy alone have failed to demonstrate a clear survival
      advantage, and concurrent chemoradiation has delivered better results than
      previously obtained with radiation therapy alone, establishing the benefit of
      adding chemotherapy. This method of treatment, together with new modalities of
      therapy and novel agents, has reintroduced the question of induction chemotherapy
      before definitive chemoradiation. Systemic chemotherapy offers a better
      possibility of reducing systemic metastasis and improving cosmetic appearance.
      This article reviews developing trends using induction chemotherapy followed by
      chemoradiation in patients with head and neck squamous cell carcinoma.

PMID- 17020456
TI  - Surgery of lymph nodes in papillary thyroid cancer.
AB  - Optimal treatment for differentiated thyroid carcinoma is controversial with
      respect to the extent of thyroid resection, the extent and technique of nodal
      dissection and use of prophylactic radioiodine treatment. Postoperative
      complications, such as recurrent laryngeal nerve injury and definitive
      hypoparathyroidism, have carried great weight in the discussion regarding how
      radical the surgical treatment should be. The discussion of whether total
      thyroidectomy or lesser procedures should be the treatment for thyroid carcinomas
      has been protracted. Now, reasonable agreement exists that total thyroidectomy is
      the best treatment and the focus of the discussion has moved to the treatment of
      lymph nodes. At the time of diagnosis, node metastases are a common finding in
      patients with differentiated thyroid cancer, in particular papillary carcinoma.
      The argument supporting a radical approach to lymph node excision is that the
      presence of node metastases increases the recurrence rate. Advocates for the
      conservative approach believe that little association exists between node
      metastases and death from thyroid carcinoma. This paper reviews relevant medical
      literature published in the English language on surgery of lymph nodes in
      differentiated thyroid cancer with well-controlled trials. Searches were last
      updated in June 2006.

PMID- 17020457
TI  - Monoclonal antibodies in chronic lymphocytic leukemia.
AB  - Multiple options are now available for the treatment of chronic lymphocytic
      leukemia. Over the last 10 years, monoclonal antibodies have become an integral
      part of the management of this disease. Alemtuzumab has received approval for use
      in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab
      has been investigated extensively in chronic lymphocytic leukemia both as a
      single agent and in combination with chemotherapy and other monoclonal
      antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the
      early phase of clinical development. This article will review the monoclonal
      antibodies more commonly used to treat chronic lymphocytic leukemia, the results
      obtained with monoclonal antibodies as single agents and in combination with
      chemotherapy, and other biological agents and newer compounds undergoing clinical
      trials.

PMID- 17020458
TI  - Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma.
AB  - Immunomodulatory drugs, such as thalidomide, lenalidomide (Revlimid, CC-5013) and
      actimid (CC-4047), have a broad spectrum of activity and have shown remarkable
      responses in patients with multiple myeloma and related hematological diseases,
      such as myelodysplastic syndrome. They are currently being tested in other cancer
      types. This review will focus on the preclinical and clinical activity of
      thalidomide and its more potent immunomodulatory derivatives that are used to
      treat multiple myeloma. They represent a new class of antitumor agents that not
      only target the tumor cell directly, but also have significant activity within
      the bone marrow milieu. These agents have shown high responses in all phases of
      multiple myeloma, including the upfront setting, relapsed refractory stage and
      also as maintenance therapy for the disease. They have been used in combination
      with dexamethasone, chemotherapy and, more recently, with other novel agents,
      such as proteasome inhibitors. Thalidomide and lenalidomide in combination with
      dexamethasone have recently been approved by the US FDA for the treatment of
      multiple myeloma.

PMID- 17020459
TI  - Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs.
AB  - Anthracyclines are a well-known cause of cardiotoxicity, but a number of other
      drugs used to treat cancer can also result in cardiac and cardiovascular adverse
      effects. Cardiotoxicity can result in the alteration of cardiac rhythm, changes
      in blood pressure and ischemia, and can also alter the ability of the heart to
      contract and/or relax. The clinical spectrum of these toxicities can range from
      subclinical abnormalities to catastrophic life-threatening, and sometimes fatal,
      sequelae. These events may occur acutely or may only become apparent months or
      years following completion of oncological treatment. Ischemia and rhythm
      abnormalities are treated symptomatically in most cases. Knowledge of these
      toxicities can aid clinicians to choose the optimal and least toxic regimen
      suitable for an individual patient.

PMID- 17020460
TI  - Breast cancer metastasis progression as revealed by intravital videomicroscopy.
AB  - Metastasis is the spread of cells from a primary tumor to a distant site, where
      they arrest and grow to form a secondary tumor. Conventional metastasis models
      have focused primarily on analysis of end point tumor formation following
      inoculation with tumor cells. This approach can be used to measure the metastatic
      potential of cell lines, the morphology of metastases and their vasculature and
      the overall effectiveness of treatment strategies. However, it cannot, reveal the
      dynamics of metastatic progression, tumor cell interactions with host tissues or
      the characteristics of blood flow within the tumor microvasculature. Intravital
      videomicroscopy has been developed to visualize and quantify the movement of
      tumor cells and their interactions with host tissues as they travel through
      metastatic pathways within the body and arrest at secondary sites. Intravital
      videomicroscopy can also be used to quantify the morphology and functional
      capacity of tumor microvasculature, as well as the timing and dynamic effects of
      drugs targeted to disrupt tumor vasculaturization. With the development of new
      fluorescent probes and reporter genes, intravital videomicroscopy has the
      potential to provide evidence of the timing and location of metabolic processes
      within the metastatic cascade that may serve as specific targets for the
      treatment of breast cancer.

PMID- 17020461
TI  - Locoregional therapy of breast cancer: maximizing control, minimizing morbidity.
AB  - The goal of locoregional therapy in breast cancer has remained unchanged for a
      century: the eradication of all malignant cells from the breast and draining
      lymph nodes, hopefully prior to them having spread to distant organs. However,
      how we accomplish this goal has changed dramatically over this time period and
      our success in achieving this goal has been greatly enhanced by improvements in
      breast imaging and systemic therapies. The therapeutic importance of surgery and
      radiation has been underestimated in recent years and is thought to have minimal
      impact on long-term outcome. More recent data have reputed this contention and
      the relationship between local control and survival in breast cancer is becoming
      increasingly apparent. This article will review the importance of attaining
      optimum local control with minimum morbidity and examine where the future of
      locoregional therapy of breast cancer may lie.

PMID- 17020462
TI  - Recent improvements in the detection and treatment of nonmuscle-invasive bladder
      cancer.
AB  - In total, 70-80% of newly diagnosed bladder cancers are confined to the mucosa
      and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph
      nodes and metastasis classification. The standard treatment for these nonmuscle
      invasive bladder cancers is transurethral tumor resection with or without
      adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent
      follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers
      two main problems. First, approximately 10-20% of all tumors are not seen in
      standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are
      bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence
      guided cystoscopy has demonstrated significantly higher tumor detection rates and
      optimized patient treatment in recent Phase III studies. Second, routinely
      performed urine cytology is characterized by high specificity but low
      sensitivity. Today, several urine tests are available that may increase
      diagnostic accuracy and potentially prolong intervals of follow-up cystocopy.
      Owing to rather high recurrence rates after transurethral tumor resection in most
      tumors and high progression rates in poorly differentiated tumors, adjuvant
      intravesical chemotherapy or intravesical immunotherapy has gained widespread use
      in patients with nonmuscle-invasive bladder cancer. Only a few further
      immunomodulatory drugs, such as recombinant cytokines, have shown significant
      clinical effectiveness. Additional approaches, such as photodynamic therapy with
      different photosensitizers and thermotherapy in combination with intravesical
      chemotherapy, have been evaluated in Phase III studies.

PMID- 17020463
TI  - Use of APO2L/TRAIL with mTOR inhibitors in the treatment of glioblastoma
      multiforme.
AB  - The mammalian target of rapamycin (mTOR) plays a critical role in the regulation
      of cell growth, proliferation and survival. Components of the mTOR pathway are
      activated in a variety of tumors, including glioblastoma multiforme (GBM), and we
      have found that one surprising consequence of mTOR pathway activation is
      resistance of GBMs to the proapoptotic effects of agents such as APO2L/TRAIL.
      mTOR inhibition has become feasible following the development of rapamycin and
      comparable analogs with improved pharmacological properties, including CCI-779,
      RAD001 and AP23573. Numerous studies have also demonstrated promising
      proapoptotic activity, with relatively mild side effects, using rapamycin analogs
      in vitro and in vivo in conjunction with APO2L/TRAIL. These studies suggest that
      mTOR inhibitors can be combined with APO2L/TRAIL as a potential tumor-selective
      therapy.

PMID- 17020464
TI  - Monitoring standards for molecular genetic testing in the United Kingdom, the
      Netherlands, and Ireland.
AB  - Molecular genetic techniques have entered many areas of clinical practice. Public
      expectations from this technology are understandably high. To maintain confidence
      in this technology, laboratories must implement the highest standards of quality
      assurance (QA). External quality assessment (EQA) is recognized as an essential
      component of QA. The United Kingdom National External Quality Assessment Service
      (UKNEQAS) for Molecular Genetics, first set up in 1991, is currently the longest
      provider of EQA to molecular genetic testing laboratories in the UK, The
      Netherlands, and Ireland. Errors in the scheme are sporadic events. However,
      evidence from this and other EQA schemes suggests that a residual error rate
      persists, which should be taken into account in clinical practice. This EQA
      scheme has evolved from the respective scientific bodies of the constituent
      countries and retains a strong emphasis on collective peer review. It is
      essential that the steps taken to ensure quality in this rapidly expanding field
      are clear and transparent to participants and public alike. We describe the
      procedures developed and the governance imposed to monitor and improve analytical
      and reporting standards in participant laboratories and we compare our
      experiences with those of equivalent EQA services in the United States.

PMID- 17020465
TI  - Novel vasopressin type 2 (AVPR2) gene mutations in Brazilian nephrogenic diabetes
      insipidus patients.
AB  - Nephrogenic diabetes insipidus (NDI) is an inherited disorder characterized by
      renal resistance to the antidiuretic effect of arginine vasopressin (AVP),
      resulting in polyuria, polydipsia, and hypoosmolar urine. In the vast majority of
      cases, NDI is associated with germ-line mutations in the vasopressin receptor
      type 2 gene (AVPR2) and in about 8% of the cases with the water channel aquaporin
      2 gene (AQP-2) mutations. To date, approximately 277 families with 185 germ-line
      mutations in the AVPR2 gene have been described worldwide. In the present study,
      the AVPR2 gene was genotyped in eight unrelated Brazilian kindred with NDI. In
      five of these NDI families, novel mutations were noted (S54R, I130L, S187R,
      219delT, and R230P), whereas three seemingly unrelated probands were found to
      harbor previously described AVPR2 gene mutations (R106C, R137H, R337X).
      Additionally a novel polymorphism (V281V) was detected. In conclusion, although
      NDI is a rare disease, the findings of mutations scattered over the entire coding
      region of the AVPR2 gene are a valuable model to determine structure function
      relationship in G-protein-coupled receptor related diseases. Furthermore, our
      data indicate that in Brazil the spectrum of AVPR2 gene mutations is "family
      specific".

PMID- 17020466
TI  - Systematic analysis of sequence variability of the endothelin-1 gene: a
      prerequisite for association studies.
AB  - We analyzed allele frequencies and pairwise linkage disequilibria of 13 variants
      in the EDN1 gene of 298 young males, the majority of German ancestry. Our
      analysis comprises all common variants in the five exons and flanking intronic
      regions, as well as known polymorphisms in the promoter sequence. In addition to
      previously analyzed polymorphisms, our haplotype reconstruction included five
      recently described variants and was done by using three different algorithms to
      allow inference of result stability. More than 30 haplotypes were predicted. All
      haplotypes with frequencies > or = 1% were inferred by all three methods and can
      be described by seven haplotype tagging single-nucleotide polymorphisms (htSNPs),
      reducing the genotyping load to 65%. Three of these haplotypes with frequencies
      of about 11%, 9%, and 4% had been mistaken for one haplotype in the previous
      analysis, which included only six polymorphisms, some of them not being htSNPs.
      Systematic analysis of sequence variability and comprehensive haplotype analysis
      of the EDN1 gene determined a substantial part of its genetic variability for
      further association studies and helped to reduce the genotyping load for common
      phenotypes.

PMID- 17020467
TI  - Molecular basis of cystic fibrosis in Lithuania: incomplete CFTR mutation
      detection by PCR-based screening protocols.
AB  - Mutational analysis of the cystic fibrosis transmembrane regulator (CFTR) gene
      was performed in 98 unrelated CF chromosomes from 49 Lithuanian CF patients
      through a combined approach in which the p.F508del mutation was first screened by
      allele-specific PCR while CFTR mutations in nonp.F508del chromosomes have been
      screened for by denaturing gradient gel electrophoresis analysis. A CFTR mutation
      was characterized in 62.2% of CF chromosomes, two of which (2.0%) have been
      previously shown to carry a large gene deletion CFTRdele2,3(21 kb). The most
      frequent Lithuanian CF mutation is p.F508del (52.0%). Seven CFTR mutations,
      p.N1303K (2.0%), p.R75Q (1.0%), p.G314R (1.0%), p.R553X (4.2%), p.W1282X (1.0%),
      and g.3944delGT (1.0%), accounted for 10.1% of Lithuanian CF chromosomes. It was
      not possible to characterize 35.8% of the CF Lithuanian chromosomes. Analysis of
      intron 8 (TG)mTn and M470V polymorphic loci did not permit the characterization
      of the CFTR dysfunction underlying the CF phenotype in the patients for which no
      CFTR mutation was identified. Thus, screening of the eight CFTR mutations
      identified in this study and of the large deletion CFTRdele2,3(21 kb) allows the
      implementation of an early molecular or confirmatory CF diagnosis for 65% of
      Lithuanian CF chromosomes.

PMID- 17020468
TI  - Robust, easy, and dose-sensitive methylation test for the diagnosis of Prader
      Willi and Angelman syndromes.
AB  - We present a new method for differential diagnosis of Prader-Willi (PWS) and
      Angelman syndromes (AS) that requires only a small amount of DNA including that
      obtained from amniocentesis specimens. This method not only proved to be robust
      and rapid, but, most importantly, it can be dosage sensitive, supplying
      additional information useful for genetic counselling. After methylation
      dependent digestion of DNA with HpaII or McrBC, exon 1 of the SNRPN gene is
      amplified together with a sequence in the CpG island of the H19 gene. Given the
      similarities in sequence composition and methylation status between the amplified
      sequences, their co-amplification under semiquantitative conditions allows an
      easy discrimination between single dosage (present in deletions or chromosomal
      translocations) and a double-dosage state (uniparental disomy or imprinting
      error), when the appropriate controls are included. The method we have developed
      in combination with standard cytogenetic studies and segregation analysis of
      microsatellite markers offers a rapid and easy procedure to resolve most
      suspected cases of PWS and AS, and consequently to provide accurate genetic
      counselling.

PMID- 17020469
TI  - Frequency of CARD15 polymorphisms in patients with Crohn's disease from Toledo,
      Spain: genotype-phenotype correlation.
AB  - Crohn's disease (CD) presents a complex multifactorial etiology with genetic and
      environmental factors contributing to the disorder. Epidemiological studies have
      shown that three major CARD15 polymorphisms, R702W, G908R, and 1007fs, are
      associated with CD. We studied the frequencies of these three polymorphisms in
      patients from Toledo, Spain, and compared them with the frequencies found in
      studies of other populations. A total of 183 patients with CD and 172 healthy
      controls from Toledo, Spain, were included in this study. All of these
      individuals were genotyped for the three CARD15 polymorphisms R702W, G908R, and
      1007fs. Frequencies were analyzed to identify any genotype-phenotype
      associations. The control population exhibited frequencies of CARD15
      polymorphisms similar to the results of previous studies, 3.4%, 1.1%, and 2.0%
      for the R702W, G908R, and 1007fs polymorphisms, respectively, whereas CD patients
      had allele frequencies of 7.6%, 3.0%, and 4.6%, respectively. Significant
      associations were found between the presence of R702W and patients carrying two
      susceptibility variants with early age of onset and stricturing pattern.

PMID- 17020470
TI  - PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like
      phenotype.
AB  - Mutations in the PTPN11 gene are known to cause a large fraction of the cases of
      Noonan syndrome. The objective of this study was to determine the PTPN11 gene
      mutation rate in a cohort of clinically well-characterized Brazilian patients
      with Noonan or Noonan-like syndromes and to study the genotype-phenotype
      correlation. Fifty probands with Noonan syndrome ascertained according to well
      established diagnostic criteria, 3 with LEOPARD syndrome, 5 with Noonan
      like/multiple giant cell lesion syndrome, and 3 with neurofibromatosis/ Noonan
      were enrolled in this study. Mutational analysis was performed using denaturing
      high-performance liquid chromatography (DHPLC) followed by sequencing of
      amplicons with an aberrant elution profile. We detected missense mutations in the
      PTPN11 gene in 21 probands with Noonan syndrome (42%), in all 3 patients with
      LEOPARD syndrome, and in 1 case with Noonan-like/multiple giant cell lesion
      syndrome. One patient with neurofibromatosis-Noonan syndrome had a mutation in
      both the PTPN11 and NF1 genes. The only anomalies that reached statistical
      significance when comparing probands with and without mutations were the
      hematological abnormalities. Our data confirms that Noonan syndrome is a
      genetically heterogeneous disorder, with mutations in the PTPN11 gene responsible
      for roughly 50% of the cases. A definitive genotype-phenotype correlation has not
      been established, but the T73I mutation seems to predispose to a
      myeloproliferative disorder. Regarding Noonan-like syndromes, mutation of the
      PTPN11 gene is the main causal factor in LEOPARD syndrome, and it also plays a
      role in neurofibromatosis-Noonan syndrome. Noonan- like/multiple giant cell
      lesion syndrome, part of the spectrum of Noonan syndrome, is also heterogeneous.

PMID- 17020471
TI  - Different genes and polymorphisms affecting high-density lipoprotein cholesterol
      levels in Greek familial hypercholesterolemia patients.
AB  - Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high
      low-density lipoprotein cholesterol (LDL-C) concentrations that frequently gives
      rise to premature coronary artery disease. The clinical expression of FH is
      highly variable, even in patients carrying the same LDL receptor gene mutation.
      This variability may be due to environmental and other genetic factors. We
      investigated the effect of APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE
      Ser128Arg, SELE Leu554Phe, and ENaCa Ala663Thr polymorphisms on the HDL-C
      variations in 84 patients with FH. For ApoCIII T1100C, subjects with the TT
      genotype presented higher HDL-C levels than the other genotype groups (p =
      0.046). Similarly the presence of the Gln allele in ADRB2 27 Glu/Gln
      heterozygotes and ADRB2 27 Gln/Gln homozygotes was associated with higher HDL-C
      levels (p = 0.014). Among the other polymorphisms tested, none of them were
      associated with variations in HDL-C levels. The influence of each polymorphism on
      lipid concentrations was evaluated with linear regression analyses after
      adjustment for age and sex. Among the variables studied including total
      cholesterol, LDL-C, high-density lipoprotein (HDL)-C, triglycerides,
      apolipoprotein A (Apo-A) and B (Apo-B), and lipoprotein alpha (LP alpha), HDL-C
      concentration was significantly different in models applied for polymorphisms
      ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04,
      respectively). These results suggest that HDL-C levels in FH heterozygotes may be
      affected by several different genetic variants.

PMID- 17020472
TI  - The P1812A and P25T BRCA1 and the 5164del4 BRCA2 mutations: occurrence in high
      risk non-Ashkenazi Jews.
AB  - Founder mutations in the BRCA1 and BRCA2 genes have been discovered in the
      Ashkenazic Jewish population, but a founder mutation(s) has not been discovered
      among non-Ashkenazi Jews (NAJ). Two BRCA1 mutations (P1812A, P25T), and a BRCA2
      mutation (5164del4) have been detected in NAJ high-risk families. We studied the
      prevalence of these three mutations in 270 high-risk NAJ families, including 85
      from Iraq/Iran, 67 from North Africa, 27 from Yemen, 50 from the Balkan region,
      and 41 with mixed ancestry. The three mutations were detected only in individuals
      related to the original families. We conclude that the P1812A and P25T BRCA1 and
      5164del4 BRCA2 mutations are not likely to be founder mutations in NAJ high-risk
      families. We also assessed the pathogenicity of the BRCA1 P1812A mutation in
      vitro using reporter gene assays in yeast and mammalian cells. We found that the
      BRCA1 P1812A variant activity assays yielded a slightly reduced reporter gene
      activity. Thus, there is some uncertainty as to the pathogenicity of BRCA1
      P1812A.

PMID- 17020473
TI  - A frequent large rearrangement in the CFTR gene in cystic fibrosis patients from
      Reunion Island.
AB  - Reunion Island is a French province, 800 km east of Madagascar and 200 km west of
      Mauritius. On Reunion Island, the birth prevalence of cystic fibrosis (CF) is
      particularly high in the population of European origin, approximately 1:1000. In
      a previous study, we demonstrated that the screening of the 27 exons of the CF
      transmembrane conductance regulator (CFTR) gene by denaturing high-pressure
      liquid chromatography (DHPLC) in 114 CF families allowed the detection of about
      93% of the molecular defects present on Reunion Island. Unidentified CF mutations
      may lie in introns or in regulatory regions that are not routinely investigated,
      or may correspond to gene rearrangements such as large, heterozygous deletions
      that escape detection using current PCR-based techniques. Using a combination of
      different methods (such as multiplex ligation-dependent probe amplification), 6
      of the 13 unidentified CF alleles (46%) were found to harbor a deletion of 5288
      bp, spanning from exon 17a to 18. Identification and examination of the
      breakpoint sequences showed that this deletion is different from the
      3120+1kbdel8.6Kb previously found in the Palestinian Arabs. The chromosomes
      bearing IVS16+3316_IVS18+644del5288 did not have a common extragenic haplotype.
      Clinical evaluation of homozygotes (2 unrelated patients) and compound
      heterozygotes indicated that this deletion represents a severe mutation
      associated with positive sweat chloride test, pancreatic insufficiency, and early
      age at diagnosis.

PMID- 17020474
TI  - Quantitative multiplex real-time PCR for detection of PLP1 gene duplications in
      Pelizaeus-Merzbacher patients.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder of central
      nervous system (CNS) myelination typically affecting males. A genomic duplication
      of variable size at Xq22.2, containing the entire proteolipid protein 1 gene
      (PLP1), is responsible for approximately 60-70% of PMD cases. The aim of this
      study was to develop a rapid and robust method for determination of PLP1 gene
      dosage. We optimized two multiplex real-time quantitative PCR (Q-PCR) assays
      targeting exons 3 and 6 of the PLP1 gene, and then validated these assays by
      retrospective analysis of a set of genomic DNAs from 67 previously tested
      patients and 43 normal controls. Samples were analyzed in multiplex PCR reactions
      using TaqMan chemistry and the ABI Prism 7000 Sequence Detection System. PLP1
      dosage was determined by the relative quantitative comparative threshold cycle
      method (DeltaDeltaCt) using the human serum albumin gene as the endogenous
      reference gene. Three clearly non-overlapping ranges of results, corresponding to
      the presence of one, two, or three PLP1 copies, were detected in both assays. The
      results were completely concordant with gender and previous PLP1 gene dosage
      testing based on quantitative fluorescent multiplex PCR and analysis of a
      dinucleotide polymorphism in the first intron of the PLP1 gene. We conclude that
      multiplex real-time Q-PCR represents a fast and reliable tool for PLP1
      duplication testing in PMD families.

PMID- 17020475
TI  - Validity and utility of a LRRK2 G2019S mutation test for the diagnosis of
      Parkinson's disease.
AB  - The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's
      disease (PD), will soon be widely available as a molecular clinical test for PD.
      The objective of this study was to assess performance characteristics of G2019S
      as a clinical test for PD in the setting of typical movement disorder clinics in
      the United States. Subjects included 1,518 sequentially recruited PD patients
      from seven movement disorder clinics in the United States, and 1,733 unaffected
      subjects. All 3,251 subjects were genotyped for the G2019S mutation using a
      TaqMan assay, and mutations were verified by direct sequencing. Test validity
      estimates were calculated using standard methods. A total of 20/1518 patients and
      1/1733 controls carried the G2019S mutation. Specificity was 99.9% (95% CI, 99.6
      100%), sensitivity was 1.3% (0.8-2.1%), and the positive likelihood ratio was
      22.8. A positive family history of PD increased the positive likelihood ratio to
      82.5. Information on gender, age at disease onset, or age at testing did not
      improve test performance. The gene test was highly accurate in classifying
      mutation carriers as PD, but it performed poorly in predicting the phenotype of
      non-mutation carriers. A G2019S molecular test for PD would be highly specific,
      technically simple, and inexpensive. Test interpretation is straightforward when
      used for diagnosis of symptomatic individuals, but is more complex for risk
      assessment and predictive testing in asymptomatic individuals. Test results can
      have psychological, social, and economical ramifications; thus, proper counseling
      is essential.

PMID- 17020479
TI  - Diffusion tensor imaging in the corpus callosum in children after moderate to
      severe traumatic brain injury.
AB  - Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the
      microstructure of the cerebral white matter (WM) based on anisotropic diffusion
      (i.e., water molecules move faster in parallel to nerve fibers than perpendicular
      to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with
      myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in
      adults with traumatic brain injury (TBI). However, previous DTI studies of
      pediatric TBI were case reports without detailed outcome measures. Using mean FA
      derived from DTI fiber tractography, we compared DTI findings of the corpus
      callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe
      TBI and individually matched, uninjured children. Interexaminer and intraexaminer
      reliability in measuring FA was satisfactory. FA was significantly lower in the
      patients for the genu, body, and splenium of the corpus callosum. Higher FA was
      related to increased cognitive processing speed and faster interference
      resolution on an inhibition task. In the TBI patients, higher FA was related to
      better functional outcome as measured by the dichotomized Glasgow Outcome Scale
      (GOS). FA also increased as a function of the area of specific regions of the
      corpus callosum such as the genu and splenium, and FA in the splenium was reduced
      with greater volume of lesions in this region. DTI may be useful in identifying
      biomarkers related to DAI and outcome of TBI in children.

PMID- 17020478
TI  - In vivo characterization of traumatic brain injury neuropathology with structural
      and functional neuroimaging.
AB  - Quantitative neuroimaging is increasingly used to study the effects of traumatic
      brain injury (TBI) on brain structure and function. This paper reviews
      quantitative structural and functional neuroimaging studies of patients with TBI,
      with an emphasis on the effects of diffuse axonal injury (DAI), the primary
      neuropathology in TBI. Quantitative structural neuroimaging has evolved from
      simple planometric measurements through targeted region-of-interest analyses to
      whole-brain analysis of quantified tissue compartments. Recent studies converge
      to indicate widespread volume loss of both gray and white matter in patients with
      moderate-to-severe TBI. These changes can be documented even when patients with
      focal lesions are excluded. Broadly speaking, performance on standard
      neuropsychological tests of speeded information processing are related to these
      changes, but demonstration of specific brain-behavior relationships requires more
      refined experimental behavioral measures. The functional consequences of these
      structural changes can be imaged with activation functional neuroimaging.
      Although this line of research is at an early stage, results indicate that TBI
      causes a more widely dispersed activation in frontal and posterior cortices.
      Further progress in analysis of the consequences of TBI on neural structure and
      function will require control of variability in neuropathology and behavior.

PMID- 17020480
TI  - Magnetic resonance spectroscopy detects brain injury and predicts cognitive
      functioning in children with brain injuries.
AB  - Proton magnetic resonance spectroscopy (1H-MRS) and neuropsychological assessment
      were utilized in a longitudinal investigation of traumatic brain injury (TBI) in
      children. A spectroscopic imaging protocol was implemented, and neurometabolite
      ratios of NAA/Cre and Cho/Cre were calculated for anterior and posterior halves
      of a supraventricular slab of brain tissue. NAA/Cre was reduced and Cho/Cre
      increased in TBI patients as compared to controls, for both brain regions. Each
      ratio predicted aspects of neuropsychological performance, though the specific
      relationships varied somewhat by region and function. Anterior NAA/Cre increased
      and anterior Cho/Cre decreased from 3 to 21 weeks post-injury, suggesting
      neurometabolic recovery.

PMID- 17020481
TI  - Measurements and models of cerebral function in the severely injured brain.
AB  - We review the emerging applications of functional and structural neuroimaging
      techniques for the assessment of patients with disorders of consciousness.
      Measurements of brain function from patients in the vegetative state (VS) and
      minimally conscious state (MCS) are compared, and a conceptual organization is
      developed that suggests models of brain mechanisms associated with different
      functional levels of recovery. We emphasize developing strategies to place
      complex brain injuries on a more equal footing using global and regional
      quantification of resting or activated brain activity using functional imaging
      techniques alongside more detailed structural assessments of neuronal integrity
      and axonal connectivity now available. Preliminary studies from several
      investigative groups suggest that some MCS patients may harbor a functional
      reserve in the form of recruitable cerebral networks. These findings support
      developing systematic characterizations of the severely injured brain and suggest
      that some patients may benefit from improved diagnostic assessments.

PMID- 17020482
TI  - Mechanisms of working memory dysfunction after mild and moderate TBI: evidence
      from functional MRI and neurogenetics.
AB  - Cognitive complaints are a frequent source of distress and disability after mild
      and moderate traumatic brain injury (TBI). While there are deficits in several
      cognitive domains, many aspects of these complaints and deficits suggest that
      problems in working memory (WM) play an important role. Functional imaging
      studies in healthy individuals have outlined the neural substrate of WM and have
      shown that regions important in WM circuitry overlap with regions commonly
      vulnerable to damage in TBI. Use of functional MRI (fMRI) in individuals with
      mild and moderate TBI suggests that they can have problems in the activation and
      allocation of WM, and several lines of evidence suggest that subtle alterations
      in central catecholaminergic sensitivity may underlie these problems. We review
      the evidence from fMRI and neurogenetic studies that support the role of
      catecholaminergic dysregulation in the etiology of WM complaints and deficits
      after mild and moderate TBI.

PMID- 17020483
TI  - Guidelines for the pharmacologic treatment of neurobehavioral sequelae of
      traumatic brain injury.
AB  - There is currently a lack of evidence-based guidelines to guide the
      pharmacological treatment of neurobehavioral problems that commonly occur after
      traumatic brain injury (TBI). It was our objective to review the current
      literature on the pharmacological treatment of neurobehavioral problems after
      traumatic brain injury in three key areas: aggression, cognitive disorders, and
      affective disorders/anxiety/ psychosis. Three panels of leading researchers in
      the field of brain injury were formed to review the current literature on
      pharmacological treatment for TBI sequelae in the topic areas of
      affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A
      comprehensive Medline literature search was performed by each group to establish
      the groups of pertinent articles. Additional articles were obtained from
      bibliography searches of the primary articles. Group members then independently
      reviewed the articles and established a consensus rating. Despite reviewing a
      significant number of studies on drug treatment of neurobehavioral sequelae after
      TBI, the quality of evidence did not support any treatment standards and few
      guidelines due to a number of recurrent methodological problems. Guidelines were
      established for the use of methylphenidate in the treatment of deficits in
      attention and speed of information processing, as well as for the use of beta
      blockers for the treatment of aggression following TBI. Options were recommended
      in the treatment of depression, bipolar disorder/mania, psychosis, aggression,
      general cognitive functions, and deficits in attention, speed of processing, and
      memory after TBI. The evidence-based guidelines and options established by this
      working group may help to guide the pharmacological treatment of the person
      experiencing neurobehavioral sequelae following TBI. There is a clear need for
      well-designed randomized controlled trials in the treatment of these common
      problems after TBI in order to establish definitive treatment standards for this
      patient population.

PMID- 17020484
TI  - Aspects on decompressive craniectomy in patients with traumatic head injuries.
AB  - In patients with traumatic brain injury (TBI), intracranial hypertension
      secondary to cerebral edema is a major problem. A last-tier treatment in these
      cases is decompressive craniectomy. The aim of the present retrospective
      investigation was to (1) study the long-time outcome in patients with traumatic
      head injuries with intracranial hypertension treated with decompressive
      craniectomy; (2) examine the effects on intracranial pressure (ICP) by the
      craniectomy; and (3) investigate the possible relationship between the size of
      the removed bone-flap and the effects on ICP. Among the about 150 patients with
      severe TBI treated at our neurointensive care unit during 1997-2002, 19 patients
      were treated with decompressive craniectomy. All patients were young (mean 22 +/-
      11 years, range 7-46 years), and 68% were male. The mean ICP was reduced from
      29.2 +/- 3.5 before to 11.1 +/- 6.0 mm Hg immediately after the craniectomy; at
      24 h after the craniectomy, the mean ICP was 13.9 +/- 9.7 mm Hg. Paired-samples t
      test revealed a statistically significant decrease, both when comparing the
      preoperative values to the values immediately postoperative as well as to the
      values after 24 h (p < 0.01). A significant correlation between the size of the
      craniectomy and the decrease in ICP was found using Pearson regression analysis.
      The outcome of all patients could be assessed. The survival rate was 89%. Two
      patients died (both day 4 after the trauma); 68% of the patients had a favorable
      outcome (Glasgow Outcome Scale [GOS] score of 4 or 5); 16% were severely disabled
      (GOS score of 3); and one patient (5%) was left in a vegetative state.

PMID- 17020485
TI  - Percutaneous implantation of cerebral microdialysis catheters by twist-drill
      craniostomy in neurocritical patients: description of the technique and results
      of a feasibility study in 97 patients.
AB  - Cerebral microdialysis is increasingly used to monitor several types of
      neurocritical patients. This study presents the technique used in our unit for
      percutaneous implantation of cerebral microdialysis catheters using a small twist
      drill craniostomy that can be performed in the intensive care unit (ICU). We also
      present the results of this technique in 89 head-injured patients and in eight
      patients with a malignant middle cerebral artery (MCA) infarction. One hundred
      and twenty-two cerebral microdialysis catheters were implanted in the 97 patients
      included in this study. One cerebral microdialysis catheter was implanted in the
      less damaged hemisphere of 67 head-injured patients with a diffuse brain injury.
      An additional microdialysis catheter was inserted in the pericontusional
      parenchyma of 22 patients with brain contusions. In five of the eight patients
      with a malignant MCA infarction, only one microdialysis probe was inserted in the
      penumbral zone. In the remaining three patients, two cerebral microdialysis
      catheters were implanted in the same hemisphere (one in the ischemic core and the
      other in the penumbra). Technical problems were detected in 18 (15%) of the 122
      microdialysis catheters implanted and were more frequent during the initial
      period of using microdialysis in our unit. In four patients (3% of implanted
      catheters), follow-up computed tomography (CT) scans showed a small intracerebral
      blood collection (always <or=1 cc) around the microdialysis catheter. There were
      no microdialysis-related infections. In conclusion, percutaneous insertion of
      single or multiple microdialysis catheters in neurocritical patients by using
      twist drill craniostomy is feasible, fast, and safe.

PMID- 17020486
TI  - Decreased expression of glutamate transporters in astrocytes after human
      traumatic brain injury.
AB  - The primary mechanism for eliminating synaptically released glutamate is uptake
      by astrocytes. In the present study, we examined whether traumatic brain injury
      (TBI) affects the cellular expression of glutamate transporters EAAT1 and EAAT2.
      Morphometrical immunohistochemical analysis demonstrated a predominant expression
      of EAAT1 and EAAT2 in astrocytes of normal human neocortex (n = 10). Following
      traumatic injury of human brain (n = 55), the number of EAAT2-positive cells was
      decreased for a prolonged survival period within the traumatized neocortex and
      the pericontusional region. GFAP-positive astrocytes decreased in number within
      the first 24 h. Thereafter, the number of GFAP-positive astrocytes increased
      again, indicating formation of reactive gliosis. Double immunofluorescence
      examinations revealed a reduction in absolute numbers of GFAP-positive astrocytes
      coexpressing EAAT1 or EAAT2 at survival times up to 7 days. In addition, the
      relative fractions of astrocytes coexpressing glutamate transporters decreased
      following TBI. We conclude that the posttraumatic reduction in cellular EAAT 1
      and EAAT2 expression is predominantly due to degeneration of astrocytes and to
      downregulation in surviving astrocytes. Our results support the view that reduced
      glutamate uptake by astrocytes contributes to posttraumatic elevation of
      extracellular glutamate in humans.

PMID- 17020487
TI  - Traumatic brain injury produces delay-dependent memory impairment in rats.
AB  - Memory impairment following traumatic brain injury (TBI) is common in both humans
      and animals. A noteworthy feature of memory dysfunction in human TBI is impaired
      memory performance that is dependent on the delay between initial learning and
      recall of information. However, previous studies of TBI-induced memory impairment
      in animals have failed to control for the initial amount of learning between sham
      and injured animals. The present study demonstrates that experimental TBI in rats
      produces delay-dependent memory impairment, even when the initial degree of
      learning is controlled for. Animals were injured at a moderate level of lateral
      fluid percussion (LFP) injury (n = 10) or received a sham injury (n = 9), and
      then trained in a water T-maze version of the delayed-non-matching-to-place
      (DNMP) task beginning 10 days post-injury. Acquisition training consisted of 15
      trials per day on post-injury days 11-15 using a minimal (7-sec) delay between
      the sample and choice phases of the task. Following acquisition, the delay
      between the sample and choice phases of the task was progressively increased to
      15, 30, and 120 sec. Injured animals acquired the task at the same rate as sham
      animals and performed equally well at the 15-sec delay (p > 0.05). However, as
      the delay increased to 30 and 120 sec, the performance of the injured animals
      deteriorated (p < 0.05). These results indicate that LFP injury produces delay
      dependent memory impairments in rats. This is therefore a valid model of an
      important feature of memory impairment in human TBI, and should be a useful
      addition to the available methods for assessing memory impairment and the effect
      of therapeutic interventions after TBI.

PMID- 17020488
TI  - Nicotinamide treatment reduces behavioral impairments and provides cortical
      protection after fluid percussion injury in the rat.
AB  - This study examined the ability of nicotinamide (vitamin B3) to improve
      functional outcome in a dose-dependent manner following fluid percussion injury
      (FPI). Injured (duration of unconsciousness mean = 85.8 sec; apnea = 9.9 sec),
      rats were administered nicotinamide (500 or 50 mg/kg; ip) or saline at 15 min and
      24 h. Serum analysis of nicotinamide concentrations were conducted 1 h following
      the last injection. Sensorimotor and cognitive tests were conducted for 35 days
      following FPI. Both the 500 and 50 mg/kg doses of nicotinamide significantly
      facilitated recovery on the vibrissae-forelimb placing test compared to saline
      treatment, which showed chronic impairments. Both treatments also significantly
      improved performance on the bilateral tactile adhesive removal test. On the
      cognitive tests, the 500 mg/kg dose, but not the 50 mg/kg dose, improved
      performance on a working memory task in the Morris water maze (MWM). However,
      acquisition of a reference memory task in the MWM was not improved. Serum
      analysis showed that the 500 mg/kg dose significantly raised nicotinamide
      concentrations by 30-fold and the 50 mg/kg dose by 3-fold compared to the saline
      administration. This study demonstrated that raising nicotinamide concentrations
      resulted in the reduction of the behavioral impairments following FPI. In fact,
      the 500 mg/kg dose prevented the occurrence of the behavioral deficits on the
      bilateral tactile removal and working memory tests. Both doses significantly
      reduced tissue loss and glial fibrillary acid protein (GFAP) expression in the
      cortex. The 500 mg/kg dose reduced GFAP expression in the hippocampus. This data
      suggests that nicotinamide has substantial preclinical efficacy for TBI, and
      there appears to be some differences in the ability of the doses to improve
      performance in the MWM.

PMID- 17020489
TI  - Recovery of function after vagus nerve stimulation initiated 24 hours after fluid
      percussion brain injury.
AB  - Recent evidence from our laboratory demonstrated in laboratory rats that
      stimulation of the vagus nerve (VNS) initiated 2 h after lateral fluid percussion
      brain injury (FPI) accelerates the rate of recovery on a variety of behavioral
      and cognitive tests. VNS animals exhibited a level of performance comparable to
      that of sham-operated uninjured animals by the end of a 2-week testing period.
      The effectiveness of VNS was further evaluated in the present study in which
      initiation of stimulation was delayed until 24 h post-injury. Rats were subjected
      to a moderate FPI and tested on the beam walk, skilled forelimb reaching,
      locomotor placing, forelimb flexion and Morris water maze tasks for 2 weeks
      following injury. VNS (30 sec trains of 0.5 mA, 20.0-Hz biphasic pulses) was
      initiated 24 h post-injury and continued at 30-min intervals for the duration of
      the study, except for brief periods when the animals were detached for behavioral
      assessments. Consistent with our previous findings when stimulation was initiated
      2 h post-injury, VNS animals showed significantly faster rates of recovery
      compared to controls. By the last day of testing (day 14 post-injury), the FPI
      VNS animals were performing significantly better than the FPI-no-VNS animals and
      were not significantly different from shams in all motor and sensorimotor tasks.
      Performance in the Morris water maze indicated that the VNS animals acquired the
      task more rapidly on days 11-13 post-injury. On day 14, the FPI-VNS animals did
      not differ in the latency to find the platform from sham controls, whereas the
      injured controls did; however, the FPI-VNS animals and injured controls were not
      significantly different. Despite the lack of significant histological differences
      between the FPI groups, VNS, when initiated 24 h following injury, clearly
      attenuated the ensuing behavioral deficits and enhanced acquisition of the
      cognitive task. The results are discussed with respect to the norepinephrine
      hypothesis.

PMID- 17020490
TI  - Impact of additional extracranial injuries on outcome after mild traumatic brain
      injury.
AB  - Many patients with mild traumatic brain injury (MTBI) concurrently sustain
      extracranial injuries; however, little is known about the impact of these
      additional injuries on outcome. We assessed the impact of additional injuries on
      the severity of postconcussional symptoms (PCS) and functional outcome 6 months
      post-injury. A questionnaire (including the Rivermead Post-Concussion
      Questionnaire and SF-36) was sent to consecutive MTBI patients (hospital
      admission Glasgow Coma Score 13-15; age range 18-60 years) admitted to the
      emergency department of a level-I trauma center, and, to serve as a baseline for
      PCS, a control group of minor-injury patients (ankle or wrist distortion). Of the
      299 MTBI respondents (response rate 52%), 89 had suffered additional injuries
      (mean Injury Severity Score [ISS] of 14.5 +/- 7.4). After 6 months, 44% of the
      patients with additional injuries were still in some form of treatment, compared
      to 14% of patients with isolated MTBI and 5% of the controls. Compared to
      patients with isolated injury, MTBI patients with additional injuries had resumed
      work less frequently and reported more limitations in physical functioning.
      Overall, they did not report higher levels of PCS, despite somewhat more severe
      head injury. Regardless of the presence of additional injuries, patients that
      were still in treatment reported significantly more severe PCS, with highest
      rates in patients with isolated MTBI. In conclusion, many patients with
      additional extracranial injuries are still in the process of recovery at 6 months
      after injury. However, despite more severe impact to the head and inferior
      functional outcomes, these patients do not report more severe PCS.

PMID- 17020491
TI  - Computational studies of strain exposures in neonate and mature rat brains during
      closed head impact.
AB  - Traumatic brain injury (TBI) is the most common cause of death in childhood, and
      the majority of fatal cases are due to motor vehicle accidents, falls, sport
      related accidents, and child abuse. Rodents and particularly rats became a
      commonly used animal model of TBI in childhood as well as in adults, and
      different techniques are described in the literature to induce the brain injury.
      However, findings reported in the last decade regarding the increased stiffness
      of brain tissue in young animals, including rats, are not considered in
      experimental designs of TBI studies, and this may seriously bias the results when
      TBI effects are compared across different animal ages. In this study, we
      determined the strain and stress distributions in neonatal (post-natal-day [PND]
      13-17) and mature (PND 43 and 90) rat brains during a closed head injury, using
      age-specific finite element (FE) models. The FE simulations indicated that for
      identical cortical displacements, the neonatal brain may be exposed to larger
      peak stress magnitudes compared with a mature brain due to stiffer tissue
      properties in the neonate, as well as larger strain magnitudes due to its smaller
      size. The brain volume subjected to a certain strain level was greater in the
      neonate brain compared with the adult models for all indentation depths greater
      than 1 mm. In conclusion, our present findings allow better design of closed head
      impact experiments which involve an age factor. Additionally, the larger peak
      stresses and larger strain volumetric exposures observed in the neonatal brain
      support the hypothesis that the smaller size and stiffer tissue of the infant
      brain makes it more susceptible to TBI.

PMID- 17020493
TI  - T cell costimulation: a rational target in the therapeutic armamentarium for
      autoimmune diseases and transplantation.
AB  - T cells are central mediators of adaptive immunity. As such, they are involved in
      both normal immune responses (e.g., rejection of a transplanted organ) and
      abnormal ones (e.g., rheumatoid arthritis). T cells require both antigen-specific
      and costimulatory signals for their full activation. Advances in protein
      engineering and an increased understanding of the immune response have culminated
      in the evolution and creation of protein therapeutics that target specific
      costimulatory molecules. The selective costimulation modulator abatacept (CTLA
      4Ig) binds to CD80 and CD86, blocking interaction with CD28, and is approved for
      the treatment of moderate to severe rheumatoid arthritis. Belatacept, currently
      enrolling phase III trials in renal transplantation, was rationally designed from
      abatacept to bind with more avidity to CD86, providing the more potent
      immunosuppressive properties required for immunosuppression in transplantation.
      This review describes the relevant immunology and summarizes recent clinical
      findings on these two molecules. Although both inhibit the CD28 costimulatory
      pathway, they are tailored for specific disease states--abatacept for autoimmune
      diseases and belatacept for transplantation.

PMID- 17020494
TI  - Proceedings of the Intercultural Cancer Council's Ninth Biennial Symposium on
      Minorities, the Medically Underserved, and Cancer.

PMID- 17020496
TI  - Patient navigation: a community centered approach to reducing cancer mortality.
AB  - BACKGROUND: Profound advances in biomedical science have contributed to increased
      longevity and improved quality of life for many Americans. Despite this progress,
      a heavier burden of disease is borne by some population groups in the United
      States, particularly the poor and underserved. Landmark reports published since
      1973 have highlighted these health disparities, explored their causal factors,
      and outlined strategies to reduce them. More recent research studies underscore
      the results of these early reports that identify social position, economic
      status, culture, and environment as critical determinants of who develops and
      survives cancer and of the quality of life of cancer survivors. METHODS: The
      Patient Navigation Program was established in Harlem, New York, in 1990 to
      address the dramatic disparities in breast cancer mortality among minority women
      in the community. RESULTS AND CONCLUSIONS: The success of the Harlem Patient
      Navigation Program has provided the impetus for the development of many similar
      patient navigation programs across the country and for federal support for
      Patient Navigation research to address the critical need for effective
      interventions to eliminate cancer health disparities, particularly among
      minorities and the underserved.

PMID- 17020497
TI  - California American Indian and Alaska natives tribal groups' care access and
      utilization of care: policy implications.
AB  - Background. We used the 2001 California Health Interview Survey (CHIS) to examine
      differences in cancer care access and utilization by subgroups of American Indian
      and Alaskan Natives (AIAN). Methods. The CHIS 2001 includes over 55,000
      Californian households, with an oversampling of California American Indian, non
      California AIAN, and unknown AIAN tribal groups. Results. We found significant
      differences among the 3 tribal subgroups for various measures of health care
      coverage and utilization. Conclusions. AIAN must be disaggregated to provide
      appropriate data for public health and policy making.

PMID- 17020498
TI  - Population science is science only if you know the population.
AB  - BACKGROUND: Cancer control efforts have had limited effect in reducing the
      inequities for minorities and the medically underserved. One factor is the lack
      of theory-based conceptualization of the terms used to define race, ethnicity,
      and culture. METHOD: Guidelines are provided to develop more accurate use of the
      terms race, ethnicity, and culture to determine standards of comparability across
      studies of cancer incidence, survival, and quality of life in diverse populations
      rather than stereotypes. RESULTS AND CONCLUSIONS: Our ability to use
      theoretically based criteria to differentiate groups of people could increase our
      ability to more effectively eliminate these disparities.

PMID- 17020499
TI  - Racial and gender disparities in hereditary colorectal cancer risk assessment:
      the role of family history.
AB  - BACKGROUND: In this study, we aimed to examine racial/ethnic and gender
      differences in self-reported family cancer history knowledge in patients at high
      risk for hereditary colon cancer syndromes. METHODS: We performed retrospective
      analysis of all referrals to the University of Chicago High Risk Colon Cancer
      Clinic between 1995 and 2003. RESULTS: We found hereditary nonpolyposis
      colorectal cancer and familial adenomatous polyposis in 17% and 9% of Whites,
      respectively, and 6% and 0% of Blacks, respectively. Unknown paternal history was
      found in 6.5% of Whites and 18.9% of Blacks (23% men, 11% women). CONCLUSIONS:
      Blacks and men had significantly decreased rates of paternal history cancer
      knowledge.

PMID- 17020500
TI  - Self-reported sleep quality in family caregivers of gastric cancer patients who
      are receiving chemotherapy in Korea.
AB  - BACKGROUND: Shifting of cancer care from inpatient to outpatient in Korea can
      lead to negative outcomes for family caregivers. Little research has been
      performed on Korean family caregivers' sleep quality and its related symptoms:
      fatigue and depression. METHODS: We obtained data from a convenient sample of 103
      family caregivers. Family caregivers completed sleep, depression, fatigue, and
      quality of life questionnaires. RESULTS: Of family caregivers, 80% had poor sleep
      quality. Positive correlation existed among symptoms, but symptoms were
      negatively correlated with quality of life. CONCLUSIONS: Health professionals
      need to include family caregivers in the overall patient care plan.

PMID- 17020501
TI  - Assessing breast cancer knowledge, beliefs, and misconceptions among Latinas in
      Houston, Texas.
AB  - BACKGROUND: Limited breast cancer knowledge and beliefs, risk factors, screening
      procedures, and cultural barriers may keep Latinas from seeking health care.
      METHOD: We examined the breast cancer knowledge, beliefs, and misconceptions of
      63 Latinas residing in Houston, Texas. RESULTS: More than a third of participants
      held a negative or fatalistic view of breast cancer, 29% believed pain was a
      warning sign for the disease, and 11.1% had never heard of breast cancer.
      CONCLUSIONS: Our findings indicate this population holds many misconceptions
      about breast cancer, which may have a negative impact on preventive behaviors on
      this minority population.

PMID- 17020502
TI  - Native Hawaiian preferences for informed consent and disclosure of results from
      genetic research.
AB  - BACKGROUND: Informed consent is generally waived when using anonymous stored
      specimens in research because individual harm is minimal; however, group harm may
      arise if specimens contain ethnic identifiers. METHODS: We assessed preferences
      for informed consent and disclosure of results from genetic research through a
      survey (N = 429, 83.2% Native Hawaiian). RESULTS: Native Hawaiians were more
      likely than non-Hawaiians to require informed consent for genetic research using
      personally identified (81% vs 77.8%), anonymous (40.9% vs 34.7%), and ethnically
      identified specimens (51.3% vs 33.3%). Most respondents wanted results reported
      to them (87.6%) and to their physicians (79.0%). CONCLUSIONS: Recognizing
      community preferences for informed consent and disclosure of research results may
      alleviate concerns about group harms inherent in genetic research.

PMID- 17020503
TI  - Cancer, minorities, and the medically underserved: A call to action.
AB  - In an edited excerpt from her opening address delivered on March 24, 2004, at the
      Ninth Biennial Symposium on Minorities, the Medically Underserved, and Cancer in
      Washington, DC, former US Surgeon General Antonia C. Novello, MD, Dr. PH,
      encouraged health professionals to dispense with "age-old approaches" that have
      failed to eliminate health disparities affecting minorities and go in a "bold new
      direction." She urges new efforts focusing on the root causes of disparities
      including lack of health insurance, lack of access to culturally sensitive and
      language-appropriate health care, and institutional racism in health care.

PMID- 17020504
TI  - Breast and cervical cancer control among Pacific Islander and Southeast Asian
      Women: participatory action research strategies for baseline data collection in
      California.
AB  - BACKGROUND: No data exists on the breast and cervical cancer screening practices
      among Cambodian, Laotian, Thai, and Tongan women. In this article, we describe
      the efforts required to conduct a baseline survey among these non-English
      speaking women using the participatory action research (PAR) approach. METHODS:
      We tailored small population sampling techniques to each of the populations in
      partnership with Community Health Outreach workers. RESULTS: A total of 1825
      surveys were successfully conducted in 8 communities. CONCLUSION: PAR and the
      culturally based techniques used to conduct the survey proved successful in
      maintaining scientific rigor, developing true community-researcher partnership,
      and achieving over 99% participation.

PMID- 17020505
TI  - Disparities, cancer surveillance, and next steps.
AB  - BACKGROUND: Effective cancer surveillance is critical for understanding
      disparities in current cancer incidence and treatment. The years ahead will see
      significant changes in how surveillance can be done. METHODS: Scenarios developed
      for the Cancer Surveillance Futures Project identify 4 paths for the next decade
      (Growth--Advances in science and technology for health care and cancer control;
      Stagnation--Hard times, slow and unequal progress on many fronts; Choice-
      Creating a healthy marketplace for health care; and Transformation--Accelerating
      cancer control for all). RESULTS AND CONCLUSIONS: In terms of getting to near
      term and longer term success with cancer surveillance, the Intercultural Cancer
      Council and C-Change have made several recommendations including consistent
      collection of socioeconomic status, risk factors, and treatment information as
      well as community involvement in collecting cancer information and developing
      cancer control approaches, developing data standards, and broadening cancer
      surveillance to include treatment quality, risk factor data, and preneoplastic
      events.

PMID- 17020506
TI  - Illuminating cancer health disparities using ethnogenetic layering (EL) and
      phenotype segregation network analysis (PSNA).
AB  - BACKGROUND: Resolving cancer health disparities continues to befuddle simplistic
      racial models. The racial groups alluded to in biomedicine, public health, and
      epidemiology are often profoundly substructured. METHODS: EL and PSNA are
      computational assisted techniques that focus on microethnic group (MEG)
      substructure. RESULTS: Geographical variations in cancer may be due to
      differences in MEG ancestry or similar environmental exposures to a recognized
      carcinogen. Examples include breast and prostate cancers in the Chesapeake Bay
      region and Bight of Biafra biological ancestry, hypertension and stroke in the
      Carolina Coast region and Central African biological ancestry, and pancreatic
      cancer in the Mississippi Delta region and dietary/medicinal exposure to safrol
      from Sassafras albidum.

PMID- 17020507
TI  - Behavioral science and the task of resolving health disparities in cancer.
AB  - BACKGROUND: Behavioral scientists use health behavior theories to assess beliefs,
      feelings, and coping styles that predict cancer screening, choice of cancer
      treatments, or postcancer quality of life. METHODS: However, research testing
      these theories is typically based on middle-class, White populations. RESULTS:
      Research needs to be culturally appropriate and relevant for minority and
      underserved populations. CONCLUSIONS: The knowledge gained from such studies will
      help in designing and evaluating culturally sensitive interventions to reduce
      health disparities by modifying unhealthy behaviors such as poor diet, smoking,
      lack of regular physical activity, or failure to get timely cancer screening.

PMID- 17020508
TI  - Pacific island partnership: the Pacific Cancer Initiative.
AB  - BACKGROUND: Cancer is a leading cause of mortality in the US Associated Pacific
      Island Nations (USAPIN) due to few resources for prevention, screening, and
      treatment. METHODS: We describe the formation of the Pacific Cancer Initiative
      (PCI), and the Cancer Council of the Pacific Islands (CCPI)to address the rising
      cancer burden in USA PIN. Since their inception, PCI and CCPI have conducted
      cancer needs assessments, developed strategic cancer plans, and acquired
      additional cancer program funding for USAPIN. RESULTS: We emphasize the
      importance of international/regional partnerships and participatory development
      in assuring sustainability of cancer programs in USAPIN. CONCLUSIONS: The USAPIN
      speak with a unified voice.

PMID- 17020510
TI  - A community-driven action plan to eliminate breast and cervical cancer disparity:
      successes and limitations.
AB  - BACKGROUND: The objective of Alabama Racial and Ethnic Approaches to Community
      Health 2010 is to implement and evaluate a community action plan (CAP) developed
      by a diverse coalition to reduce breast and cervical cancer screening disparities
      between African American and White women. METHODS: The CAP entailed (1)
      establishing a core working group (CWG) in each county, (2) training CWG members
      to promote screenings, and (3) providing coalition members with technical
      assistance to write mini-grants. RESULTS: Overall, 241 CWG members were trained.
      They have conducted 2800 cancer screening surveys. A total of 8 coalition members
      received mini-grants. CONCLUSION: Community capacity building can lead to a sense
      of ownership and empowerment.

PMID- 17020511
TI  - "Have fun ... I hope you learn something".

PMID- 17020514
TI  - Teaching residents chronic disease management using the Flinders model.

PMID- 17020515
TI  - Distance learning for communicating cancer, culture, and literacy: a model for
      cancer control advancement.
AB  - BACKGROUND: Successful cancer control communications and research must reflect an
      understanding and appreciation of the importance of cultural, linguistic, and
      literacy needs of diverse audiences. The Cancer, Culture and Literacy Institute,
      a National Cancer Institute-funded R25 educational project, blends traditional
      learning approaches with distance learning methodologies to reach demographically
      dispersed cancer control researchers with new knowledge and skills on culture and
      literacy. We report here the distance learning component of the project. METHODS:
      A Web-based learning management system was developed that consisted of three
      elements: (1) educational modules, (2) communications, and (3) resources.
      RESULTS: Results from 64 doctorally prepared participants demonstrated high
      satisfaction with the content, high usefulness of materials, and very good to
      excellent stimulation of thinking. CONCLUSIONS: Distance learning offers a
      promising and appealing vehicle for communicating cancer control skills,
      interventions, and best practices, and thus has the potential to impact the
      appropriateness of cancer communications, research, and education.

PMID- 17020516
TI  - Health parties for African American study recruitment.
AB  - Innovative strategies are needed to increase minorities' research participation.
      Using existing social networks within the African American community, "home
      health parties" were tested as a way to recruit African American women to a
      breast cancer control study. Parties included social, educational, and
      recruitment components. All women attending health parties consented, completed a
      survey, and received the study's preliminary breast cancer risk assessment. There
      were no differences in rates of participation for subsequent study components
      between women recruited via parties versus other methods. Health parties are
      viable recruitment strategies, reduce barriers to participation, provide a
      supportive environment, and are relatively inexpensive.

PMID- 17020517
TI  - Cancer research training: the Southwest Oncology Group young investigator
      training program (YITP).
AB  - BACKGROUND: Recognizing the growing need for an infusion of new investigators
      into the cancer researchers, and realizing that well-trained cancer researchers
      are a dying breed, the Southwest Oncology Group (SWOG) initiated the Young
      Investigator Training Program (YITP) in 1999, supported by the Hope Foundation.
      The first author was one of four applicants accepted in 2004 and is reporting on
      this experience. METHODS: After a rigorous and competitive application process,
      four physicians beginning their career in Hematology-Oncology are chosen each
      year. Each investigator would have submitted an original research concept. Each
      class receives intensive training in statistical principles, data collection and
      analysis, critical decision making, and protocol development guidelines. Each
      investigator spends 4 days at the SWOG operations office in San Antonio, Texas,
      and 4 days at the statistical center in Seattle, Washington. RESULTS: As part of
      the training course, each investigator will design a clinical protocol that will
      be reviewed by the appropriate disease committees within SWOG. Once approved, it
      will be submitted to the National Cancer Institute for further review. The four
      investigators will receive a certificate at the successful completion of the
      training course and will be recognized at the group meeting. With the class of
      2004, 31 investigators will have joined the ranks of seasoned researchers.
      Fifteen protocols have been introduced and activated at institutions across the
      United States. Four other protocols are in various stages of the development and
      approval process. CONCLUSION: The Hope Foundation sponsored SWOG YITP is a unique
      opportunity. It allows participants to acquire a thorough understanding of the
      conduct of cancer clinical trials through SWOG. Large institutions are urged to
      continue sponsoring similar programs. This will build an infrastructure of well
      trained cancer researchers to foster and continue the progress achieved in cancer
      research.

PMID- 17020518
TI  - Using focus groups to develop interventions to promote colorectal cancer
      screening among Vietnamese Americans.
AB  - BACKGROUND: Colorectal cancer is the third most common cancer in Vietnamese
      Americans. Their colorectal screening rates are lower than the rates of whites.
      METHODS: Four focus groups were conducted to identify Vietnamese American sources
      and credibility of health information, media utilization, and intervention
      approaches. RESULTS: Vietnamese Americans trusted doctors and patient
      testimonials and had access to, and received most of their health information
      from, Vietnamese- language print and electronic media. Recommended intervention
      approaches include promoting doctors' recommendation of screening and using
      Vietnamese-language mass media, print materials, and oral presentations.
      CONCLUSIONS: Focus groups are useful in determining communication channels and
      intervention approaches.

PMID- 17020519
TI  - Physician and patient influences on the rate of colorectal cancer screening in a
      primary care clinic.
AB  - BACKGROUND: Colorectal cancer (CRC) screening rates remain low, despite
      widespread recommendations. The study purpose was to ascertain whether lack of
      CRC screening is attributable to physicians' failure to address CRC screening or
      to patients' failure to comply with physician recommendation. This relationship
      was also examined over time. METHODS: Retrospective chart review of 400
      preventive health visits. RESULTS: Physicians appropriately addressed screening
      16.5% of the time during 1998-1999 and 51% of the time during 2002-2003 (P <or=
      .001). The rate of test completion by patients was 53% in 1998-1999 and 31% in
      2002-2003, resulting in completed CRC screening rates of 5% and 16.5%,
      respectively (P <or= .001). CONCLUSIONS: Further education is needed, especially
      to target patient barriers to CRC screening test completion.

PMID- 17020520
TI  - The role of nutrition in oncology: a need for a change of attitude and
      curriculum.
AB  - BACKGROUND: The role of nutrition in cancer is poorly understood by Indian
      oncologists, who are exposed to minimal education on nutrition in their
      undergraduate and postgraduate careers. METHODS: A postal questionnaire survey,
      without reminder, assessed the knowledge and beliefs about nutrition of 120
      oncologists in India (response rate = 58%). RESULTS: There was a lack of teaching
      and understanding by surgeons and radiation and medical oncologists about the
      role of nutrition in prevention, carcinogenesis, treatment, and outcome.
      CONCLUSIONS: There needs to be much more emphasis in undergraduate and
      postgraduate education about the supportive role of nutrition in cancer.

PMID- 17020522
TI  - Breast cancer counts: numeracy in breast cancer information on the Web.
AB  - BACKGROUND: The purpose of this study was to determine the numeracy information
      included in three prominent breast cancer Web sites. METHODS: A content analysis
      was performed, grouping numeracy items into 15 categories. Interrater reliability
      was high. RESULTS: Of the 3,206 items identified, 14.3% were numbers, 33.9% were
      descriptive measures (e.g., many, lower), 27.3% were statistical terms (e.g.,
      predictive, risk), and 12.4% were temporal terms (e.g., before, always).
      CONCLUSIONS: Findings suggest that there is an abundance of numeric information
      presented in breast cancer Web sites, much of which may be conceptually too
      advanced for the intended audience.

PMID- 17020523
TI  - Developing an academic-community partnership for research in prostate cancer.
AB  - Community-based participatory research (CBPR) is an important strategy for
      reducing racial disparities in health outcomes. Academic-community partnerships
      are central to CBPR; however, there are few examples of how to develop these
      partnerships for prostate cancer research. This report describes the methods used
      to develop an academic-community partnership between investigators at the
      University of Pennsylvania and members of the Philadelphia chapter of the
      National Black Leadership Initiative on Cancer for CBPR on quality of life
      following prostate cancer diagnosis. Our experiences demonstrate that a
      significant investment of time is needed to identify a community partner for
      prostate cancer research and develop an effective partnership.

PMID- 17020524
TI  - Healing hearts: laughter and learning.
AB  - BACKGROUND: Cultural values of Alaska Native people acknowledge laughter as good
      medicine. It is heard in their words and stories. METHODS: To investigate how and
      in what ways laughter impacts learning from the learners' perspective, cancer
      education course evaluations were reviewed and a survey administered. RESULTS:
      94% (235/259) of Community Health Aides and Community Health Practitioners
      surveyed emphasized the importance of laughter to support adult learning. Written
      comments are grouped into three main themes: (1) supporting a comfortable
      learning community, (2) relieving stress, and (3) enhancing learning. DISCUSSION:
      This study demonstrates the value and significance of laughter to support people
      in their learning journey.

PMID- 17020527
TI  - Current animal models of bronchial asthma.
AB  - Human asthma is on the rise worldwide. The necessity to develop effective
      treatments against it requires an organized effort which covers every aspect of
      the disease from the pathological alterations via the genetic background to the
      use and development of active remedies. In these processes animal experiments
      have served an indispensable role. As asthma is not a natural disease in the
      animal kingdom the variety for artificially established animal models is quite
      wide. The possible selection ranges from the laboratory mouse to the horse, it
      includes ferret and sheep and even favorite pets such as cats and dogs. The large
      number of the models indicates that to some extent they might not be appropriate
      or it means that there is no generally accepted model of human asthma. Whatever
      the reason for this diversity animal models helped us to understand the detailed
      pathogenesis of some aspects of the disease, they helped us to develop compounds
      which are more active then previously used ones, and these models proved to us
      that human asthma is a unique, possibly species-specific disease the eradication
      of which requires a huge effort. This enormous task should include the
      collaboration of the clinical and basic research for the development of improved,
      advanced animal models, which in turn could strengthen our understanding about
      human asthma.

PMID- 17020528
TI  - Pharmacogenomics of asthma.
AB  - Patient response to asthma therapy is consistently observed to be heterogeneous.
      Pharmacogenomics is the study of inherited differences in interindividual drug
      disposition and effects, with the goal of selecting the optimal drug therapy and
      dosage for each patient. This review will cover selected examples of gene
      polymorphisms that influence the outcome of asthma therapy, and whole-genome
      expression studies using microarray technology that have shown tremendous
      potential for benefiting asthma pharmacogenomics. The utility of the mouse as an
      experimental system for pharmacogenomic discovery will also be discussed in the
      context of asthma therapy.

PMID- 17020529
TI  - Phosphodiesterase 7A: a new therapeutic target for alleviating chronic
      inflammation?
AB  - Over the last fifteen years there has been much excitement in the idea that
      targeting phosphodiesterase (PDE) 4 with small molecule inhibitors could lead to
      the discovery of novel, steroid-sparing compounds with utility in treating a
      multitude of diseases associated with chronic inflammation. However, dose
      limiting side effects, of which nausea and vomiting are the most common are
      worrisome, have hampered their clinical development. Indeed, a fundamental
      obstacle that still is to be overcome by the pharmaceutical industry is to make
      compounds that dissociate beneficial from the adverse events. Unfortunately, both
      of these activities of PDE4 inhibitors represents an extension of their
      pharmacology and improving the therapeutic ratio has proved to be a major
      challenge. Several strategies have been considered, with some degree of success,
      but compounds with an optimal pharmacophore still have not been reported. An
      alternative approach to targeting PDE4 is to inhibit other cAMP PDE families that
      are also expressed in immune and pro-inflammatory cells in the hope that the
      beneficial activity can be retained at the expense of side effects. One such
      candidate is PDE7A. In this article we review the literature on PDE7A and explore
      the possibility that selective small molecule inhibitors of this enzyme family
      could provide a novel approach to alleviate the inflammation that is associated
      with many inflammatory diseases including asthma, chronic obstructive pulmonary
      disease, atopic dermatitis, psoriasis, lupus, rheumatoid arthritis and multiple
      sclerosis.

PMID- 17020530
TI  - Nitric oxide in asthma therapy.
AB  - The discovery of the delicate role of endogenous nitric oxide in the homeostasis
      of various cellular functions and the dynamic behaviour of the airways, has led
      to a new, rapidly progressing area of physiological science, that has direct
      bearing for our understanding of multiple airway diseases. The potentially
      protective effects of nitric oxide include: neuromodulation by mediating
      inhibitory non-cholinergic non-adrenergic nerve activity; smooth muscle
      relaxation, attenuating airway hyperresponsiveness to bronchoconstrictor stimuli
      and immune-suppression. NO itself or SNO can be administered directly to the
      airways, and the development of gene transfer therapy seems to become a realistic
      approach in the treatment of airway diseases. However, NO has also harmful
      effects, especially when it interacts with other molecules. At present, there are
      novel opportunities to modulate nitric oxide-synthesis aimed to restore the
      balance between the protective and deleterious effects of nitric oxide. This is
      potentially beneficial in both airway and alveolar diseases. Such interventions
      might be targeted in various ways, e.g. by using selective reactive nitrogen- and
      oxygen- scavengers, selective NO donors and selective nitric oxide synthase
      inhibitors. The possible therapeutical opportunities are reviewed in this paper.
      Nitric oxide has already made it from the bench to the bedside, and it is likely
      that new developments in this area will drastically change respiratory medicine
      during the coming 5-10 years.

PMID- 17020531
TI  - Biopharmaceutical therapeutics for asthma remodeling.
AB  - Current asthma therapy is aimed at controlling disease symptoms. A subset of
      asthma patients remains symptomatic despite optimal therapy indicating that an
      unmet medical need exists for these patients. Innovative therapeutics are needed
      to treat the unmet need in asthma and biopharmaceutical approaches may provide an
      opportunity for identifying these agents. It is proposed that airway remodeling
      contributes to asthma symptoms and this feature of disease pathology may be a
      target for future therapies. The current review focuses on the contribution of
      one feature of airway remodeling, subepithelial fibrosis, towards disease and
      highlights some of the mechanisms that may contribute to this feature of airway
      remodeling. Further, some potential molecular targets are identified for
      consideration for therapeutic intervention.

PMID- 17020532
TI  - Corticosteroid design for the treatment of asthma: structural insights and the
      therapeutic potential of soft corticosteroids.
AB  - Inhaled and intranasal corticosteroids (ICSs) still are the most effective
      treatment available for allergic airway diseases and are likely to remain the
      cornerstone of managing persistent asthma/allergic rhinitis in the foreseeable
      future. Even if the therapeutic index of this class increased significantly with
      the introduction of newer corticosteroids, and even if new therapeutic potentials
      are beginning to emerge with our increasing understanding of the mechanisms of
      asthma, chronic obstructive pulmonary disease, and rhinitis, corticosteroid
      development still remains a very important field for drug designers. After a
      brief review of issues related to the structure-activity relationships of
      glucocorticoids and the main determinants of their receptor-binding affinity at
      the glucocorticoid receptor, the main focus of the present article will be on the
      development of soft corticosteroids, as they are particularly well suited to
      separate local activity from systemic side effects, which still is an important
      issue for ICSs. Design consideration required in the search for safe and
      effective soft drugs on one hand, and safe and effective ICSs on the other hand,
      will be briefly discussed and illustrated with a number of cases, in particular,
      with that of loteprednol etabonate and etiprednol dicloacetate, soft
      corticosteroids that are being developed for a full spectrum of therapeutic
      applications including asthma and allergic rhinitis.

PMID- 17020533
TI  - Advances in asthma and COPD treatment: combination therapy with inhaled
      corticosteroids and long-acting beta 2-agonists.
AB  - Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA)
      in addition to inhaled corticosteroids (ICS) in patients whose asthma is
      uncontrolled by ICS alone, thereby addressing two processes fundamental to
      asthma: bronchoconstriction and inflammation. Superior control--including a
      reduction in severe exacerbations--of asthma and COPD by ICS/LABA combination
      therapy has been demonstrated. Results from clinical studies suggest additive and
      potentially synergistic effects when the two agents are used in combination. No
      new safety-related issues have been identified with ICS/LABA compared with the
      monocomponents. The exact mechanisms for the enhanced efficacy of ICS/LABA
      combinations are under investigation but likely include drug interactions at the
      receptor level and interwoven signalling pathways, which may result in improved
      function of 2- adrenoceptors and steroid receptors. Data from preclinical studies
      provide evidence of additive, compensatory, complementary and synergistic effects
      of ICS and LABA in the control of inflammation and airway and lung remodelling.
      These effects may contribute to the improved efficacy seen when treating asthma
      and COPD with ICS/LABA combinations in clinical studies. Two ICS/LABA combination
      products are available: budesonide/formoterol (Symbicort) and
      salmeterol/fluticasone propionate (SeretideTM). An ICS/LABA combination in a
      single inhaler represent safe, effective and convenient treatment options for the
      management of patients with asthma and COPD. Clinical results also suggest that
      adjustable dosing with budesonide/formoterol provides better asthma control than
      fixed dosing. Further elucidation of the underlying mechanisms responsible for
      this superior disease control is needed.

PMID- 17020534
TI  - Immune stimulatory strategies for the prevention and treatment of asthma.
AB  - The severity and incidence of asthma has dramatically increased in the developed
      nations over the last decades. Although the reason for this development is
      unknown, epidemiological studies and experimental data have lead to the
      suggestion that this phenomenon is associated with the decline of infectious
      diseases, which induce T helper 1 and/or T regulatory responses. Supporting this
      view are recent publications showing that animals can be protected from
      developing asthma by using different immune stimulatory strategies. One approach
      is based on vaccinations using live or killed bacteria or their components, CpG
      ODNs or DNA vaccination, which all induce allergen-specific or unspecific Th1
      responses. Th1 responses lead to the production of IFN-gamma, IL-12, IL-18 and IL
      23, thereby inhibiting Th2 responses and thus the development of asthma. A
      further strategy both for the prevention and therapy of asthma is the induction
      of Tr cells. Tr cells have also been shown to suppress allergic Th2 responses,
      however, in contrast to Th1 cells through a cell/cell contact mediated mechanism
      or by the secretion of the anti-inflammatory cytokines IL-10 and/or TGF-beta.
      Furthermore, there is growing information on how to induce Tr cells both in
      animals and humans. Here we review the data showing that animals can be protected
      from developing asthma by immune stimulation leading to Th1 or Tr responses.
      Possible future human use and safety of the described strategies are also
      discussed.

PMID- 17020535
TI  - Treatment of allergic asthma by targeting transcription factors using nucleic
      acid based technologies.
AB  - There is considerable evidence that T-helper 2 (Th2) cells play a central role in
      the pathogenesis of allergic diseases such as bronchial asthma, hay fever or food
      allergy. The differentiation of naive T cells into Th2 cells producing a specific
      pattern of cytokines is tightly controlled and regulated by transcription
      factors. Thus down-regulation of mRNA-levels of a single transcription factor
      leads to a "knock-down" of several mediators simultaneously, representing an
      advantage compared to earlier approaches involving down-regulation of one
      intercellular inflammatory mediator, which is unlikely to influence all
      pathophysiological aspects of the disease. We review the impact of specific and
      master transcription factors involved in Th2 cell commitment and evaluate
      approaches for the down-regulation of these proteins by degradation of their mRNA
      using nucleic-acid based technologies including antisense oligonucleotides,
      ribozymes, DNAzymes, decoys oligonucleotides and RNA interference.

PMID- 17020536
TI  - Evidence that the mechanism of antibody-catalysed hydrolysis of arylcarbamates
      can be determined by the structure of the immunogen used to elicit the catalytic
      antibody.
AB  - A kinetically homogeneous anti-phosphate catalytic antibody preparation was shown
      to catalyse the hydrolysis of a series of O-aryl N-methyl carbamates containing
      various substituents in the 4-position of the O-phenyl group. The specific nature
      of the antibody catalysis was demonstrated by the adherence of these reactions to
      the Michaelis-Menten equation, the complete inhibition by a hapten analogue, and
      the failure of the antibody to catalyse the hydrolysis of the 2-nitrophenyl
      analogue of the 4-nitrophenylcarbamate substrate. Hammett sigma-rho analysis
      suggests that both the non-catalysed and antibody-catalysed reactions proceed by
      mechanisms in which development of the aryloxyanion of the leaving group is well
      advanced in the transition state of the rate-determining step. This is probably
      the ElcB (elimination-addition) mechanism for the non-catalysed reaction, but for
      the antibody-catalysed reaction might be either ElcB or B(Ac)2 (addition
      elimination), in which the elimination of the aryloxy group from the tetrahedral
      intermediate has become rate-determining. This result provides evidence of the
      dominance of recognition of phenolate ion character in the phosphate hapten in
      the elicitation process, and is discussed in connection with data from the
      literature that suggest a B(Ac)2 mechanism, with rate-determining formation of
      the tetrahedral intermediate for the hydrolysis of carbamate substrates catalysed
      by an antibody elicited by a phosphonamidate hapten in which phenolate anion
      character is minimized. The present paper contributes to the growing awareness
      that small differences in the structure of haptens can produce large differences
      in catalytic characteristics.

PMID- 17020537
TI  - Interaction of mammalian Hsp22 with lipid membranes.
AB  - Hsp22/HspB8 is a member of the small heat-shock protein family, whose function is
      not yet completely understood. Our immunolocalization studies in a human
      neuroblastoma cell line, SK-N-SH, using confocal microscopy show that a
      significant fraction of Hsp22 is localized to the plasma membrane. We therefore
      investigated its interactions with lipid vesicles in vitro. Intrinsic tryptophan
      fluorescence is quenched in the presence of lipid vesicles derived from either
      bovine brain lipid extract or purified lipids. Time-resolved fluorescence studies
      show a decrease in the lifetimes of the tryptophan residues. Both of these
      results indicate burial of some tryptophan residues of Hsp22 upon interaction
      with lipid vesicles. Membrane interactions also lead to increase in fluorescence
      polarization of Hsp22. Gel-filtration chromatography shows that Hsp22 binds
      stably with lipid vesicles; the extent of binding depends on the nature of the
      lipid. Hsp22 binds more strongly to vesicles made of lipids containing a
      phosphatidic acid, phosphatidylinositol or phosphatidylserine headgroup (known to
      be present in the inner leaflet of plasma membrane) compared with lipid vesicles
      made of a phosphatidylcholine head-group alone. Far-UV CD spectra reveal
      conformational changes upon binding to the lipid vesicles or in membrane-mimetic
      solvent, trifluoroethanol. Thus our fluorescence, CD and gel-filtration studies
      show that Hsp22 interacts with membrane and this interaction leads to stable
      binding and conformational changes. The present study therefore clearly
      demonstrates that Hsp22 exhibits potential membrane interaction that may play an
      important role in its cellular functions.

PMID- 17020538
TI  - The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex
      with the inhibitor Gly-Phe-CHN2.
AB  - hDDPI (human dipeptidyl peptidase I) is a lysosomal cysteine protease involved in
      zymogen activation of granule-associated proteases, including granzymes A and B
      from cytotoxic T-lymphocytes and natural killer cells, cathepsin G and neutrophil
      elastase, and mast cell tryptase and chymase. In the present paper, we provide
      the first crystal structure of an hDPPI-inhibitor complex. The inhibitor Gly-Phe
      CHN2 (Gly-Phe-diazomethane) was co-crystallized with hDPPI and the structure was
      determined at 2.0 A (1 A=0.1 nm) resolution. The structure of the native enzyme
      was also determined to 2.05 A resolution to resolve apparent discrepancies
      between the complex structure and the previously published structure of the
      native enzyme. The new structure of the native enzyme is, within the experimental
      error, identical with the structure of the enzyme-inhibitor complex presented
      here. The inhibitor interacts with three subunits of hDPPI, and is covalently
      bound to Cys234 at the active site. The interaction between the totally conserved
      Asp1 of hDPPI and the ammonium group of the inhibitor forms an essential
      interaction that mimics enzyme-substrate interactions. The structure of the
      inhibitor complex provides an explanation of the substrate specificity of hDPPI,
      and gives a background for the design of new inhibitors.

PMID- 17020539
TI  - Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion
      and improve glucose tolerance in female rats.
AB  - Pravastatin, irbesartan and captopril are frequently used in the treatment of
      patients with Type 2 diabetes. These drugs also exert beneficial metabolic
      effects, causing an improved glucose tolerance in patients, but the precise
      mechanisms by which this is achieved remain elusive. To this end, we have studied
      whether these drugs influence insulin secretion in vivo through effects on islet
      blood perfusion. Captopril (3 mg/kg of body weight), irbesartan (3 mg/kg of body
      weight) and pravastatin (0.5 mg/kg of body weight) were injected intravenously
      into anaesthetized female Wistar rats. Blood flow rates were determined by a
      microsphere technique. Blood glucose concentrations were measured with test
      reagent strips and serum insulin concentrations were measured by ELISA.
      Pancreatic blood flow was markedly increased by pravastatin (P<0.001), captopril
      (P<0.05) and irbesartan (P<0.01). Pancreatic islet blood flow was significantly
      and preferentially enhanced after the administration of captopril (P<0.01),
      irbesartan (P<0.01) and pravastatin (P<0.001). Kidney blood flow was enhanced
      significantly by pravastatin (P<0.01), irbesartan (P<0.05) and captopril
      (P<0.01). Captopril and pravastatin also enhanced late-phase insulin secretion
      and positively influenced glycaemia in intraperitoneal glucose tolerance tests.
      In conclusion, the present study suggests that a local pancreatic renin
      angiotensin system and pravastatin treatment may be selectively controlling
      pancreatic islet blood flow, augmenting insulin secretion and thereby improving
      glucose tolerance. Our findings indicate significant gender-related differences
      in the vascular response to these agents. Since statins and renin-angiotensin
      system inhibitors are frequently used by diabetic patients, the antidiabetic
      actions of these drugs reported previously might occur, in part, through the
      beneficial direct islet effects shown in the present study.

PMID- 17020540
TI  - Plasma concentration of Fas/Fas ligand and left ventricular function in response
      to metoprolol in conjunction with standard treatment.
AB  - Recent studies suggest that cardiac myocyte apoptosis contributes to the progress
      of CHF (congestive heart failure). In the present study, we tested the hypothesis
      that metoprolol in conjunction with the standard treatment regime for CHF [an ACE
      (angiotensin-converting enzyme) inhibitor, diuretics and digoxin] may
      significantly reduce the plasma concentrations of the apoptotic mediators sFas
      (soluble Fas) and sFasL (soluble Fas ligand) in patients with CHF. An ELISA was
      used to determine the plasma concentrations of sFas and sFasL in 106 patients
      with stable CHF at recruitment. Echocardiography was performed at baseline and
      after 1 year of treatment with metoprolol in conjunction with the standard
      treatment regime for CHF (i.e. an ACE inhibitor, diuretics and digoxin). The dose
      of metoprolol was doubled on a biweekly basis up to 50 mg twice a day or
      maintained at the maximum tolerated dose. Data after 1 year were available for 92
      patients and were analysed. The plasma concentrations of sFas and sFasL in
      patients with CHF decreased significantly (P<0.01) after 1 year of treatment with
      metoprolol in conjunction with the standard treatment regime compared with at
      baseline (5.4+/-0.2 compared with 3.2+/-0.1 ng/ml respectively for sFas, and
      52.1+/-2.3 compared with 26.7+/-1.0 pg/ml respectively for sFasL). Compared with
      baseline, after 1 year of treatment with metoprolol in conjunction with the
      standard treatment regime there were significant improvements in LV (left
      ventricular) ejection fraction (from 32.6+/-0.9 to 51.5+/-0.8%; P<0.01), LV end
      diastolic dimension (from 69.8+/-0.6 to 57.7+/-0.3 mm; P<0.01), LV end-systolic
      dimension (from 53.9+/-0.6 to 40.5+/-0.5 mm; P<0.01), LV end-diastolic volume
      (from 254.7+/-5.0 to 164.1+/-2.2 ml; P<0.01) and LV end-systolic volume (from
      142.0+/-4.2 to 72.2+/-2.0 ml; P<0.01). In addition, the distance walked in a 6
      min walk test increased markedly (P<0.01) from 260.3+/-5.2 m at baseline to
      440.9+/-5.7 m after 1 year of treatment. In conclusion, we have demonstrated that
      metoprolol in conjunction with an ACE inhibitor, diuretics and digoxin in
      patients with CHF can lead to a reverse in LV remodelling potentially through its
      anti-apoptotic effects.

PMID- 17020541
TI  - Comparison of extracellular matrix in skin and saphenous veins from patients with
      varicose veins: does the skin reflect venous matrix changes?
AB  - Varicose vein disease is a frequently occurring pathology with multifactorial
      causes and a genetic component. An intense remodelling of the varicose vein wall
      has been described and could be at the origin of its weakness and altered
      elasticity. We have described previously a dysregulation of collagen synthesis in
      cultured smooth muscle cells from saphenous veins and in dermal fibroblasts from
      the skin of patients with varicose veins, suggesting a systemic defect in their
      connective tissue. The present study describes comparative morphological and
      immunohistochemical data in both the skin and saphenous veins of eight control
      subjects (undergoing coronary bypass surgery) and eight patients with varicose
      veins. Histological staining of glycoproteins, the elastic fibre network and
      collagen bundles showed that the remodelling and fragmentation of elastic fibres
      observed in varicose veins were also present in the skin of the patients. When
      compared with control subjects, we observed in both the veins and skin of
      patients with varicose veins (i) an increase in the elastic network, as
      quantified by image analysis; (ii) an accumulation of collagen type I, fibrillin
      1 and laminin; and (iii) an overproduction of MMP (matrix metalloproteinase)-1,
      MMP-2 and MMP-3, analysed by immunohistochemistry, but normal levels of other
      MMPs (MMP-7 and MMP-9) and their inhibitors (TIMP-1, TIMP-2 and TIMP-3). An
      imbalance of extracellular matrix production/degradation was thus observed in
      veins as well as in the skin of the patients with varicose veins and, taken
      together, these findings show that remodelling is present in different organs,
      confirming systemic alterations of connective tissues.

PMID- 17020542
TI  - Cereal rust fungi genomics and the pursuit of virulence and avirulence factors.
AB  - Rust diseases cause significant reductions annually in yield of cereal crops
      worldwide. Traditional monoculture cropping systems apply significant selection
      pressure on the pathogen to cause rapid shifts in pathotypes. Plant breeders
      strive to stay ahead of the evolving pathogens by releasing new crop genotypes
      with new rust resistance genes or gene combinations. Owing to the limited number
      of known resistance genes and the lack of molecular understanding of the plant
      pathogen interaction, rusts remain challenging organisms to study, both at
      organismal and molecular levels. This review discusses recent progress by a
      number of laboratories towards better understanding the molecular component of
      rust disease resistance.

PMID- 17020543
TI  - Treatment of Streptococcus mutans with antisense oligodeoxyribonucleotides to
      gtfB mRNA inhibits GtfB expression and function.
AB  - We examined the effects of phosphorothioate-modified antisense
      oligodeoxyribonucleotides (PS-ODN) targeted to mRNA transcribed from gtfB, which
      encodes synthesis of water-insoluble glucans in Streptococcus mutans. Treatment
      of S. mutans with 10 muM antisense PS-ODNs inhibited gtfB mRNA transcription,
      GtfB expression and water-insoluble glucan synthesis. The architecture of
      biofilms formed by antisense PS-ODNs-treated S. mutans showed reduced biomass,
      more dispersed distribution with enlarged interspaces and fewer layers of
      attached cells. PS-ODN treatment had no effect on the growth of S. mutans. Our
      results indicated that it might be feasible to use antisense PS-ODN as a novel
      agent in caries prevention.

PMID- 17020544
TI  - A universal stress protein of Porphyromonas gingivalis is involved in stress
      responses and biofilm formation.
AB  - Porphyromonas gingivalis is recognized as one of the major periodontal pathogens
      in subgingival plaque, which is implicated in the progression of chronic
      periodontal disease. We analyzed the role of upsA in P. gingivalis 381 and its
      uspA-deficient mutant CW301 under various stress conditions. In general, the uspA
      mutant was less tolerant to a variety of environmental stresses relative to the
      parental strain. In addition, gene expression of uspA is upregulated during
      biofilm formation. Biofilm formation of the uspA mutant was also less than that
      of strain 381. In conclusion, the uspA gene affecting the stress responses of P.
      gingivalis is required for optimal biofilm formation.

PMID- 17020545
TI  - The unusual extended signal peptide region of the type V secretion system is
      phylogenetically restricted.
AB  - The plasmid encoded toxin, Pet, is a prototypical member of the serine protease
      autotransporters of the Enterobacteriaceae. In addition to the passenger and beta
      domains typical of autotransporters, in silico predictions indicate that Pet
      possesses an unusually long N-terminal signal sequence. The signal sequence can
      be divided into five regions termed N1 (charged), H1 (hydrophobic), N2, H2 and C
      (cleavage site) domains. The N1 and H1 regions, which we have termed the extended
      signal peptide region, demonstrate remarkable conservation. In contrast, the N2,
      H2 and C regions demonstrate significant variability and are reminiscent of
      typical Sec-dependent signal sequences. Despite several investigations, the
      function of the extended signal peptide region remains obscure and surprisingly
      it has not been proven that the extended signal peptide region is actually
      synthesized as part of the signal sequence. Here, we demonstrate that the
      extended signal peptide region is present only in Gram-negative bacterial
      proteins originating from the classes Beta- and Gammaproteobacteria, and more
      particularly only in proteins secreted via the Type V secretion pathway:
      autotransporters, TpsA exoproteins of the two-partner system and trimeric
      autotransporters. In vitro approaches demonstrate that the DNA region encoding
      the extended signal peptide region is transcribed and translated.

PMID- 17020546
TI  - Development of species-specific PCR primer sets for the detection of Leptospira.
AB  - Spirochetes of the genus Leptospira infect animals and humans and are the
      causative agents for the emerging infectious disease leptospirosis. Rapid and
      simple assays for the identification of individual Leptospira species are
      currently not available. For identification of individual Leptospira species, PCR
      primers that detect the ompL1 gene sequence for the majority of pathogenic
      leptospires were developed in this study. The primer pairs detect Leptospira
      interrogans, Leptospira borgpetersenii, Leptospira kirschneri, Leptospira
      santarosai, Leptospira weilii and Leptospira noguchii, without cross-reacting
      with other Leptospira species. The development of the primers revealed a
      divergence of the ompL1 gene within L. interrogans, splitting this species into
      two separate groups. The species-specific primers will be especially useful in
      epidemiological studies and disease outbreak investigations for the detection of
      Leptospira species in human, animal and environmental samples.

PMID- 17020547
TI  - Cloning, disruption and protein secretory phenotype of the GAS1 homologue of
      Pichia pastoris.
AB  - The aim of the study was the identification, cloning and disruption of the GAS1
      homologue of Pichia pastoris. Gas1p is a glycoprotein anchored to the outer layer
      of the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor. Gas1p
      is a beta-1,3-glucanosyltransglycosylase (EC 2.4.1.-). This cross-linking enzyme
      highly affects the structure and permeability of the yeast cell wall. The gene
      coding for the GAS1 homologue of P. pastoris was cloned by PCR, and its
      functionality was proven in a Saccharomyces cerevisiae GAS1 null mutant. Based on
      the nucleotide sequence information of the P. pastoris GAS1 homologue, a
      disruption cassette was constructed for the knockout of the GAS1 in P. pastoris.
      The morphology of DeltaGAS1 P. pastoris was identical to that of S. cerevisiae
      GAS1 mutants. Finally, the impact of GAS1 disruption on secretion of three
      recombinant model proteins in P. pastoris, human trypsinogen, human serum albumin
      and Rhizopus oryzae lipase, was evaluated. While the disruption had no effect on
      the secretion of trypsinogen and albumin, the amount of lipase released from the
      cells was doubled.

PMID- 17020548
TI  - Resistance to vanadium in Pseudomonas fluorescens ATCC 17400 caused by mutations
      in TCA cycle enzymes.
AB  - Vanadium inhibits the growth of Pseudomonas fluorescens ATCC 17400 in the low
      iron casamino acids medium and even more when iron is added to the medium.
      Analysis of transposon mutants allowed the isolation of two mutants with
      increased resistance to vanadium. One mutant had an insertion in the idh gene
      coding for the tricarboxylic acid enzyme isocitrate dehydrogenase. The second
      mutant had the transposon inserted into acnD, one out of three genes coding for a
      2-methyl-isocitrate dehydratase (aconitase). In this mutant, there was a higher
      level of acnB aconitase transcripts while the levels of acnA transcripts were
      unchanged. A nonpolar idh mutant was obtained, which showed the same level of
      resistance against vanadium as the original transposon mutant.

PMID- 17020549
TI  - New nematicidal azaphilones from the aquatic fungus Pseudohalonectria adversaria
      YMF1.01019.
AB  - Two new azaphilone metabolites, named pseudohalonectrin A (1) and B (2), were
      isolated from the culture of the aquatic fungus Pseudohalonectria adversaria
      YMF1.01019, originally separated from submerged wood in Yunnan Province, China.
      Pseudohalonectrin A and B were assessed for their nematicidal activity against
      the pine wood nematode Bursaphelenchus xylophilus and their structures were
      defined after spectral analysis. This is the first report of secondary
      metabolites from any member of the genus Pseudohalonectria.

PMID- 17020550
TI  - Inhibitory effects of sulfamic acid on three thiosulfate-oxidizing
      chemolithotrophs.
AB  - Sulfamate is an analogue of thiosulfate, and the sodium and potassium salts of
      sulfamic acid inhibited the chemolithoautotrophic growth on thiosulfate of
      Acidithiobacillus ferrooxidans and Halothiobacillus neapolitanus. The chemo
      organotrophic growth of Paracoccus versutus on sucrose was similarly inhibited by
      sulfamate. Thiosulfate oxidation by suspensions of H. neapolitanus was, however,
      unaffected by sulfamate, showing that sulfamate did not directly affect
      thiosulfate uptake, activation or oxidation. Inhibition of P. versutus was not
      relieved by cysteine and methionine, indicating that sulfate uptake and sulfur
      amino acid biosynthesis were not directly affected by sulfamate. Sulfamate was
      not degraded by any of the bacteria, and so could not serve as an alternative to
      thiosulfate as an energy-yielding substrate. Sulfamate is also an analogue of
      ammonia and might act like hydrazine by inhibiting ammonium uptake or an
      essential enzyme activity.

PMID- 17020551
TI  - The mshA gene encoding the glycosyltransferase of mycothiol biosynthesis is
      essential in Mycobacterium tuberculosis Erdman.
AB  - Mycothiol is the major low-molecular-weight thiol found in actinomycetes,
      including Mycobacterium tuberculosis, and has important antioxidant and
      detoxification functions. Gene disruption studies have shown that mycothiol is
      essential for the growth of M. tuberculosis. Because of mycothiol's unique
      characteristics, inhibitors directed against mycothiol biosynthesis have
      potential as drugs against M. tuberculosis. Four genes have been identified in
      mycobacteria that are involved in the biosynthesis of mycothiol. Two genes, mshB
      and mshD, are not essential for growth of M. tuberculosis. Mutants in these genes
      produce significant amounts of mycothiol or closely related thiol compounds. A
      targeted gene disruption in the mshC gene is lethal for M. tuberculosis,
      indicating that MshC is essential for growth. The remaining gene, mshA, encodes
      for a glycosyltransferase. In the present study, we attempted to produce a
      directed knock-out of the mshA gene in M. tuberculosis Erdman but found that this
      was only possible when a second copy of mshA was first incorporated into the
      chromosome. Bacteria with only a single copy of mshA that grew after mutagenesis
      produced normal levels of mycothiol. We therefore conclude that the mshA gene,
      like the mshC gene, is essential for the growth of M. tuberculosis.

PMID- 17020552
TI  - A novel ICE in the genome of Shewanella putrefaciens W3-18-1: comparison with the
      SXT/R391 ICE-like elements.
AB  - A novel R391-like ICE (integrating conjugative element) has been detected in the
      4.2 MB genome of Shewanella putrefaciens W3-18-1 located on three different
      contigs. Assembly of the ICE encoding contigs based on similarity with R391
      revealed a mosaic element of plasmid, phage and transposon-like sequences typical
      of SXT/R391 ICE-like elements. The element, which is 110 057 bp in length, was
      highly similar to R391 sequences, with most related ORFs showing >96% amino acid
      sequence identity. The element, designated ICESpuPO1, contained a number of
      inserts determining resistance to copper and other heavy metals and a broad
      spectrum RND efflux pump similar to antibiotic efflux systems. The element was
      integrated into the Shewanella prfC gene in a manner similar to related ICE-like
      elements. The chromosomal element junctions contained a 17-bp SXT/R391-like attL
      and attR site and an unannotated ORF between attL and the ICE integrase encoding
      a putative recombinational directional factor necessary for excision, with 100%
      amino acid identity to the R391 ORF4 product.

PMID- 17020553
TI  - Two type IV pili of Vibrio parahaemolyticus play different roles in biofilm
      formation.
AB  - Vibrio parahaemolyticus RIMD2210633 has two sets of type IV-A pilus genes. One
      set is similar to that found in other Gram-negative bacteria, such as Pseudomonas
      aeruginosa, Vibrio cholerae (chitin-regulated pilus; ChiRP), and Vibrio
      vulnificus. The other is homologous to the genes for the mannose-sensitive
      hemagglutinin (MSHA) pilus. In this study, we analyzed the effects of the
      deletions in the pilin genes for each type IV pilus (the ChiRP and the MSHA
      pilus) on biofilm formation. Although the MSHA pilin mutant formed aggregates,
      the number of bacteria that attached directly to the coverslip was reduced,
      suggesting that this pilus contributes to the bacterial attachment to the surface
      of the coverslip. In contrast, the ChiRP mutant attached to the surface of the
      coverslip, but did not form aggregates, suggesting that ChiRP plays a role in
      bacterial agglutination during biofilm formation. These results suggest that the
      two type IV pili of V. parahaemolyticus contribute to biofilm formation in
      different ways. Both mutants showed a lower fitness for adsorption onto chitin
      particles than that of the wild type. Collectively, these data suggest that the
      use of two type IV pili is a refined strategy of V. parahaemolyticus for survival
      in natural environments.

PMID- 17020554
TI  - Interaction of clinical isolates of Streptococcus pneumoniae with human
      complement factor H.
AB  - PspC recruits complement factor H (FH) to the pneumococcal surface. While there
      is differential expression of pspC during infection, detection of PspC on the
      surface of viable pneumococci is difficult due to variability among PspCs. We
      analyzed FH binding to detect PspC expression on the surface of pneumococcal
      isolates from different pathological sources. Using flow cytometry, we
      investigated FH-binding to 89 low-passage clinical isolates classified by disease
      manifestation (systemic, mucosal, or carriage). Carriage isolates recruited
      significantly more FH to their surfaces than either systemic or mucosal isolates,
      and this binding was independent of capsular serotype.

PMID- 17020555
TI  - Novel gene members in the Pho regulon of Escherichia coli.
AB  - The transcriptome profiles of the wild-type and the phoB mutant strains were
      compared at the time point showing the highest expression levels of the phoB and
      phoR genes under a P-limiting condition. Among the 18 new putative genes that
      were found to be under the control of the PhoB transcriptional regulator, five
      genes that contain the consensus Pho box were identified by sequence analysis. A
      reporter gene assay was carried out by fusing the upstream regions of these genes
      to the promoterless enhanced green fluorescent protein gene, followed by
      expression. It was found that the expressions of the amn (AMP nucleosidase), yibD
      (metal ion stress response gene) and ytfK (hypothetical protein) genes were
      activated by PhoB. These results indicate the additional roles of PhoB as a
      global regulator.

PMID- 17020556
TI  - An octameric prokaryotic glutamine synthetase from the haloarchaeon Haloferax
      mediterranei.
AB  - The glutamine synthetase (EC 6.3.1.2) from the haloarchaeon Haloferax
      mediterranei has been purified and characterized in order to understand the
      ammonium assimilation in haloarchaea. Based on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and gel-filtration chromatography, the enzyme
      consists of eight subunits of 51.7 kDa, suggesting that this enzyme belongs to
      the glutamine synthetase type II. The purified enzyme has been characterized with
      respect to its optimum temperature (45 degrees C) and pH value (8.0). The optimal
      NaCl or KCl concentrations for the reaction were 0.5 and 0.25 M, respectively.
      The effect of l-methionine-d, l-sulphoximine and different divalent metal ions
      has also been tested. The glutamine synthetase presented here is unusual; it
      shows the typical characteristic of eukaryotic and soil bacteria glutamine
      synthetases.

PMID- 17020557
TI  - Antimicrobial activities of amino acid derivatives of monascus pigments.
AB  - Amino acid derivatives of monascus pigments were produced by fermentation, and
      their antimicrobial activities were determined. Thirty-nine l- and d-forms of
      amino acids were added as a precursor to the fermentation medium for derivation
      of pigments. Derivatives with L-Phe, D-Phe, L-Tyr, and D-Tyr exhibited high
      activities against Gram(+) and Gram(-) bacteria with MIC values of c. 4-8 microg
      mL(-1). The control red pigment exhibited minimal inhibitory concentration (MIC)
      values higher than 32 microg mL(-1). Derivatives with L-Asp, D-Asp, L-Tyr, and D
      Tyr were effective against the filamentous fungi Aspergillus niger, Penicillium
      citrinum, and Candida albicans. Monascus derivatives of amino acids having a
      phenyl ring like Phe and Tyr derivatives showed high antimicrobial activities.
      Incubation of the l-Phe derivative with Bacillus subtilis caused cells to
      aggregate with formation of pellets. Easy adsorption of the L-Phe pigment
      derivative to the surface of Escherichia coli cells was observed via SEM and TEM.
      Addition of monascus pigment derivatives decreased the oxygen uptake rate of E.
      coli in culture. The antimicrobial activities of pigment derivatives are
      considered to be related to the reduced availability of oxygen for the cells
      adsorbed with pigment.

PMID- 17020558
TI  - Impaired polyhydroxybutyrate biosynthesis from glucose in Pseudomonas sp. 14-3 is
      due to a defective beta-ketothiolase gene.
AB  - Pseudomonas sp. 14-3 accumulates polyhydroxybutyrate (PHB) from octanoate, but
      not from glucose. To elucidate this unusual phenotype, genes responsible for the
      synthesis of PHB were cloned and analyzed. A PHB polymerase gene (phaC) was found
      downstream from genes coding for a beta-ketothiolase (phaA), an acetoacetyl
      coenzyme A reductase (phaB) and a putative transcriptional regulator (phaR). All
      genes were similar to pha genes from several related species, but differences
      were observed in the distal region of phaA. Complementation with heterologous
      beta-ketothiolase genes from Azotobacter sp. FA8 or Pseudomonas putida GPp104
      restored the capability of Pseudomonas sp. 14-3 to synthesize PHB from glucose,
      demonstrating that its beta-ketothiolase was nonfunctional. Analysis of the
      genome sequences of other Pseudomonas species has revealed the existence of
      putative beta-ketothiolase genes. The functionality of one of these thiolase
      genes, belonging to P. putida GPp104, was experimentally demonstrated.
      Pseudomonas sp. 14-3 is the first natural phaA mutant described, that despite
      this mutation accumulates high amounts of PHB when growing on fatty acids.

PMID- 17020559
TI  - Effect of postconditioning on coronary blood flow velocity and endothelial
      function and LV recovery after myocardial infarction.
AB  - OBJECTIVE: Postconditioning is a novel approach to myocardial protection during
      ischemia reperfusion. Our study observed the effect of postconditioning on
      coronary blood flow velocity and endothelial function in patients who underwent
      emergency percutaneous coronary intervention (PCI). METHODS: Ninety-four patients
      with their first acute myocardial infarction who underwent revascularization
      within 12 hours of onset by primary PCI were recruited in the study. All the
      patients were randomized to two groups, IR group (PCI without postconditioning)
      and Postcond group (PCI with postconditioning). Corrected TIMI frame count (CTFC)
      was used to evaluate velocity of coronary blood after PCI. Creatine phosphokinase
      (CK), CK-MB, and malondialdehyde (MDA) were measured before and after PCI.
      Arterial endothelial function was studied noninvasively by examination of
      brachial artery responses to endothelium-dependent and endothelium-independent
      stimuli by echo Doppler technique. Wall motion score index (WMSI) was assessed by
      two-dimensional echocardiography before and 8 weeks after angioplasty. RESULTS:
      There were no significant differences between the two groups with regard to age,
      sex, presence of angiographically visible collaterals, and elapsed time from the
      onset of symptoms until perfusion. Patients with postconditioning had much faster
      CTFC than patients without postconditioning (25.38 +/- 5.35 vs 29.23 +/- 5.54).
      After 8 weeks, the WMSI improved significantly in both groups, but the DeltaWMSI
      in Postcond group was significantly larger than that of IR group (1.20 +/- 0.30
      vs 1.04 +/- 0.36, P < 0.05). There was a significant negative correlation between
      DeltaWMSI and CTFC in IR group and Postcond group (r = -0.9032, P < 0.01; r = 
      0.7884, P < 0.01). The peaks of CK and CK-MB of Postcond group were much lower
      than that of IR group (1236.57 +/- 813.21 U/L vs 1697.36 +/- 965.74 U/L; 116.92
      +/- 75.83 U/L vs 172.41 +/- 92.64 U/L), and MDA-reactive products were
      significantly lower than that in the IR group at any same time after PCI. All
      patients with acute myocardial infarction had a depressed endothelium-dependent
      vasodilation function, while the endothelium-dependent vasodilation function was
      improved in Postcond group. CONCLUSION: Postconditioning is a simple, operative
      procedure for salvaging the coronary endothelial function and cardiomyocyte. It
      could be used widely in clinic and to better the prognosis of acute myocardial
      infarction.

PMID- 17020561
TI  - Age-based differences of percutaneous coronary intervention in the drug-eluting
      stent era.
AB  - INTRODUCTION: Limited data are available on contemporary percutaneous coronary
      intervention (PCI) practice patterns and outcomes in elderly patients. The
      objective of this study was to evaluate "real-world" PCI in elderly and
      nonelderly patients during the first year of availability of drug-eluting stents
      (DES) in the United States market (May 1, 2003-April 30, 2004). METHODS: One
      thousand one hundred sixty-six consecutive patients (272 elderly [age > or =75
      years] and 894 nonelderly [age <75 years]) having PCI for de novo coronary artery
      disease (CAD) at Dartmouth-Hitchcock Medical Center were included in this study.
      Primary outcome measures of this study were in-hospital major adverse cardiac
      events (MACE-death, new MI, urgent revascularization). Secondary end points
      included acute renal failure, respiratory failure, and vascular complications.
      RESULTS: Elderly patients had higher MACE (8.5% vs 1.5%, P < or = 0.001),
      unadjusted in-hospital mortality (7.4% vs 0.8%, P < or = 0.001), in-hospital
      cardiac arrest (1.5% vs 0.3%, P = 0.03), requirements for assisted blood pressure
      support (13.2% vs 7.0%, P = 0.0001), respiratory failure (2.2% vs 0.9%, P =
      0.08), acute renal failure (2.9% vs 0.8%, P = 0.005), and vascular complications
      (10.3% vs 5.5%, P = 0.005) than their nonelderly counterparts. Higher MACE rates
      persisted in the elderly despite correction for baseline differences using
      multivariate regression modeling. CONCLUSIONS: Advanced age remains a predictor
      of adverse outcomes attending PCI even in the contemporary era in which DES are
      available. This study highlights the need for further progress and investigation
      to optimize outcomes of PCI in the elderly.

PMID- 17020560
TI  - Predictors of recurrent in-stent restenosis after beta-radiation: An analysis
      from the START 40/20 trial.
AB  - OBJECTIVE: The purpose of this study was to identify potential predictors,
      including clinical, procedural, angiographic, and intravascular ultrasound (IVUS)
      parameters, for recurrent in-stent restenosis (ISR) following beta-radiation
      90Strontium/Yttrium (90Sr/Y) in a large multicenter trial. BACKGROUND: Although
      adjunct brachytherapy reduces recurrent ISR after primary catheter-based
      intervention, recurrence of stenosis after brachytherapy still occurs. METHODS:
      We analyzed 185 IVUS cohort patients in the STent And Restenosis Therapy (START)
      40/20 trial where a 40-mm, 90Sr/Y, radioactive source train was exclusively used
      for treatment of ISR to be treatable with a 20-mm balloon. RESULTS: Thirty-nine
      patients underwent target lesion revascularization. Preliminary univariate
      analysis showed that age, smoking, balloon/artery ratio, geographic miss, minimum
      lumen diameter, and diameter stenosis at baseline were associated with target
      lesion revascularization, while none of IVUS variables were (minimum lumen area,
      minimum stent area, or residual plaque burden). The multivariate logistic
      regression analysis showed that younger age, lower balloon/artery ratio, and
      presence of geographic miss were independent predictors of target lesion
      revascularization. CONCLUSIONS: Even with adjunct beta-radiation therapy, initial
      mechanical optimization, such as appropriate balloon sizing and positioning, may
      be critical for the prevention of recurrent ISR.

PMID- 17020562
TI  - The relationship of body mass index to outcomes after percutaneous coronary
      intervention.
AB  - OBJECTIVES: To evaluate the effect of body mass index (BMI) on in-hospital
      outcomes in patients undergoing percutaneous coronary intervention (PCI) at a
      tertiary care hospital center in Ontario, Canada. BACKGROUND: Obesity is present
      in a large population of patients undergoing revascularization with PCI. METHODS:
      Retrospective analysis of 4,631 patients aged 62.0 +/- 12 years, stratified by
      BMI into five groups: nonobese (<25 kg/m2); overweight (25-29.9 kg/m2); class I
      obese (30-34.9 kg/m2); class II obese (35-39.9 kg/m2); and class III obese (> or
      =40 kg/m2). RESULTS: A BMI >25 kg/m2 was present in 79% of patients, and 35% were
      obese (BMI > or =30 kg/m2). Obese patients, particularly the class III obese,
      were significantly younger and had higher prevalence of diabetes, hypertension,
      and dyslipidemia (P < 0.0001). After adjustment for several covariates, lower BMI
      was independently associated with higher risk of major bleeding requiring
      transfusion (adjusted odds ratio [OR]= 1.40, 95% confidence interval [CI] 1.04
      1.88, P = 0.025), and femoral hematoma (adjusted OR = 1.14, 95% CI 1.05-1.25, P =
      0.003) in lean (<20 kg/m2) and normal BMI (20-24.9 kg/m2) patients. Obesity was
      not associated with death, myocardial infarction, repeat PCI, coronary artery
      bypass grafting, or major adverse cardiac event. CONCLUSIONS: Obesity is not
      associated with increased risk of adverse postprocedural in-hospital outcomes.
      These findings, however, do not discount the need for sustained efforts in
      secondary prevention of obesity and its consequences.

PMID- 17020563
TI  - Proceedings of TCT: current status of catheter-based mitral valve repair
      therapies.
AB  - A variety of advances have recently facilitated development of methods to treat
      mitral regurgitation using catheter techniques via the percutaneous route. These
      include placing devices into the coronary sinus to support the mitral annulus and
      direct percutaneous leaflet repair. These approaches are already attractive for
      use in older patients and will hopefully make treatments available to many with
      no current options.

PMID- 17020564
TI  - Coronary venous capture of contrast during angiography.
AB  - Contrast-induced nephropathy (CIN) after angiographic procedures results in
      significant morbidity, mortality, and costs. Given the limitations of current
      prophylactic measures, we have tested the hypothesis that the majority of the
      contrast injected into a coronary artery can be captured from the coronary sinus
      before it enters the systemic circulation. The current study involves coronary
      venous capture after coronary angiography in dogs with determination of contrast
      capture using quantitative fluoroscopy. Venous contrast capture (VCC) was
      achieved with a balloon tipped through lumen catheter introduced into the
      coronary sinus via the superior vena cava. After selective injection of iohexol
      contrast into the left main coronary artery, the coronary sinus was balloon
      occluded in order to capture all contrast. The venous blood was subsequently
      withdrawn from the coronary sinus catheter, and then the balloon was deflated. By
      quantitative fluoroscopy we could demonstrate that an average 70 +/- 6% of the
      injected contrast could be captured without complications. Coronary sinus VCC is
      a novel approach to remove the majority of contrast selectively injected into
      coronary arteries. As an adjunct procedure in coronary angiography, VCC has the
      potential to significantly reduce the risk of CIN in patients at risk.

PMID- 17020565
TI  - Overview of pharmacology and clinical trials program with the zotarolimus-eluting
      endeavor stent.
AB  - Despite considerable benefits associated with current drug-eluting stents (DES),
      continued attention to the safety, efficacy, and deliverability of first
      generation DES has led to the development of new antiproliferative agents with
      alternative stent platforms and different drug carrier systems. Zotarolimus is a
      recently developed pharmacologic agent with both antiproliferative and anti
      inflammatory properties. The Endeavor drug-eluting stent (Medtronic Vascular,
      Santa Rosa, CA) represents the combination of zotarolimus, a low-profile cobalt
      alloy stent platform, and a biocompatible phosphorylcholine drug carrier system.
      At present, four clinical trials examining the safety and efficacy of the
      Endeavor stent have been performed. Although these studies have enrolled patients
      with similar clinical and angiographic characteristics, they have differed in
      trial design and study population size and have been performed across a broad
      geographic and physician distribution. Despite these differences, the results of
      these trials demonstrate consistently low rates of angiographic restenosis and
      repeat revascularization in addition to a favorable safety profile, with no
      occurrences of late stent thrombosis through 1 year of follow-up. This review
      describes the pharmacology and design on the Endeavor stent, summarizes results
      from recent clinical trials evaluating the Endeavor stent, and provides an
      overview of ongoing and future directions for clinical investigation.

PMID- 17020566
TI  - Update on bioabsorbable stents: from bench to clinical.
AB  - Permanent metallic stents are associated with limitations such as continued
      mechanical stress, transfer to the tissue, and continued biological interaction
      with the surrounding tissue. They are also associated with late stent thrombosis
      and artifacts when non-invasive technologies such as MRI and MSCT are used. The
      potential advantages of bioabsorbable polymeric or metallic stents are to leave
      no stent behind, they are fully compatible with MRI and MSCT imaging, and are not
      associated with late stent thrombosis. This review covers the different stent
      programs as they move from bench to bed and clinical trials. Bioabsorbable stents
      are considered the next frontier of stenting and we will discuss their potential
      to fulfill this promise in interventional cardiology.

PMID- 17020567
TI  - An overview of the TAXUS Express, paclitaxel-eluting stent clinical trial
      program.
AB  - Restenosis remains a problem following percutaneous coronary intervention in
      patients with coronary artery disease. Drug-eluting stents (DES), which combine
      mechanical and pharmacologic properties, have been shown to prevent or reduce
      neointimal growth after deployment. This review describes the TAXUS paclitaxel
      eluting stent clinical trial expansion program (TAXUS Express, Boston Scientific,
      Natick, MA). This program comprises the largest data set of randomized controlled
      trials (RCTs) of DES to date, with over 6,200 patients enrolled since 2000. The
      program includes treatment of de novo lesions, as well as higher-risk lesion and
      patient populations. In this review, we discuss the results from the TAXUS family
      of randomized clinical trials, and compare the findings with data from TAXUS
      registries. The data from the randomized clinical trials suggest that the
      paclitaxel-eluting stent provides consistent and durable benefits across multiple
      lesion and patient types. Evidence from peri-and post-approval registries, where
      patient populations are more heterogeneous than those eligible and included in
      the RCTs, corroborate these findings, with overall low rates of cardiac events,
      including reinterventions.

PMID- 17020568
TI  - Off-label use: an industry perspective on expanding use beyond approved
      indications.
AB  - The use of a medical device outside of its approved label is commonly referred to
      as "off-label use." Off-label use arises when physicians see the opportunity to
      leverage an approved therapy for an unmet patient need. This practice typically
      occurs on a case by case basis without clear documentation of indication,
      frequency, or outcomes. Sponsors have a responsibility to consider formal
      indication expansion depending on the actual use, how well the therapy fits the
      unmet need, product iteration cycles, adoption speed, resource demands, and the
      clinical risk to benefit ratio. This responsibility is particularly relevant for
      breakthrough technologies where adoption patterns can span a variety of uses. For
      Boston Scientific's drug-eluting stent program, a surveillance program was
      developed in collaboration with the FDA to compile information on practice
      patterns and safety outcomes for the TAXUS Express2 Paclitaxel-Eluting Coronary
      Stent System. The ARRIVE program has used a Web-based format to collect real-time
      data on TAXUS stent use. This >7,000 patient registry documents both on-label and
      off-label use and key safety measures for the TAXUS stent. This real-world
      registry has successfully provided a data-driven approach to BSC's product
      development strategy, including the initiation of formal label expansion
      programs. For complex or combination products, more innovative ways of capturing
      risk to benefit data are needed to define off-label use and to maximize the
      potential therapeutic utility as supported by safety data.

PMID- 17020569
TI  - Aspirin and clopidogrel resistance: consideration and management.
AB  - The efficacy with aspirin and clopidogrel treatment has been demonstrated in
      various clinical trials. Laboratory evaluation of platelet response in recent
      studies revealed that a distinctive response variability and
      nonresponsiveness/resistance in selected patients were associated with these
      antiplatelet agents. Moreover, some studies have correlated this
      nonresponsiveness/resistance phenomenon to the occurrence of thrombotic events.
      At this time there are no uniformly established methods to quantify exvivo
      platelet reactivity after clopidogrel and aspirin treatment of the extent of
      platelet inhibition by clopidogrel and aspirin. Therefore, specific treatment
      recommendations for patients exhibiting high platelet reactivity or poor platelet
      inhibition during clopidogrel or aspirin therapy are not established. A higher
      aspirin dose and strict compliance to therapy may overcome the occurrence of
      "aspirin resistance" in selected patients. A higher clopidogrel dose may be
      considered in patients exhibiting clopidogrel nonresponsiveness.

PMID- 17020570
TI  - The evolving role of glycoprotein IIb/IIIa inhibitor therapy in contemporary care
      of acute coronary syndrome patients.
AB  - Results from clinical trials of glycoprotein IIb/IIIa(GPIIb/IIIa) inhibitors
      during the past decade have established their current role in the treatment of
      non-ST-segment elevation acute coronary syndrome and in percutaneous coronary
      interventions. However, there are still unanswered questions on optimal use of
      GPIIb/IIIa inhibitors. Moreover, as new concomitant or alternative medications
      become available, the role of GPIIb/IIIa inhibitors must be reconsidered. This
      review discusses, in the light of clinical trials recently presented, what we
      know, what we are learning, and what we still need to learn.

PMID- 17020571
TI  - Debate of adjunctive pharmacology for percutaneous coronary intervention:
      anticoagulation and clopidogrel are not (always) enough.
AB  - Substantial controversy exists regarding the optimal pharmacologic cocktail for
      percutaneous coronary intervention (PCI). The most common approach typically
      includes aspirin, clopidogrel, unfractionated heparin (or enoxaparin), and
      (variably) a glycoprotein (GP) IIb/IIIa inhibitor. Some substitute bivalirudin
      with "bail-out" GP IIb/IIIa blockade for heparin and planned GP IIb/IIIa integrin
      blockade, an approach that necessarily includes aspirin and clopidogrel (for
      their antiplatelet effects). These shifts in adjunctive treatment paradigms
      should be examined in the context of available data from clinical studies.
      Several studies have demonstrated the phenomenon of clopidogrel resistance to be
      fairly prevalent; even in clopidogrel-responsive patients, steady state is
      achieved only 4-6 hours after a 600-mg loading dose. It would thus be anticipated
      that clopidogrel-resistant patients would benefit from GP IIb/IIIa blockade,
      particularly during the period immediately after intervention. Neither REPLACE-2
      nor the recent ACUITY trial demonstrated an efficacy advantage for bivalirudin as
      a substitute for heparin plus GP IIb/IIIa blockade; instead, any advantage
      appears to be limited to reducing the propensity for bleeding. As bleeding is
      directly correlated with the degree of anticoagulation and is further augmented
      by GP IIb/IIIa blockade, an alternative to the bivalirudin strategy is to simply
      reduce the amount of heparin anticoagulation during PCI. Finally, the benefit-to
      risk ratio of aggressive adjunctive antiplatelet/antithrombotic therapy might be
      further improved via risk stratification, with patients at higher risk for
      periprocedural events receiving intensive therapy and lower-risk patients being
      managed with less intensive regimens focused on minimizing the risk of bleeding.

PMID- 17020572
TI  - Debate of adjunctive pharmacology for percutaneous coronary intervention:
      thrombin inhibitors and clopidogrel are enough.
AB  - The role of adjunctive pharmacology for percutaneous coronary intervention (PCI)
      has been extensively studied, but controversy remains regarding the optimal
      regimen. While older studies suggest that glycoprotein IIb/IIIa inhibitors (GPI)
      should be routinely administered, much of this evidence was collected prior to
      the era of widespread stenting and thienopyridine use. There is now substantial
      clinical evidence that bivalirudin monotherapy is the optimal adjunctive
      pharmacology for the vast majority of patients undergoing elective or urgent
      percutaneous coronary intervention (PCI), including those presenting with an
      acute coronary syndrome (ACS). Bivalirudin monotherapy provides similar
      protection from ischemic complications with a reduced rate of major hemorrhage,
      resulting in a superior net clinical outcome compared with the use of GPI.

PMID- 17020574
TI  - Regulation of DNA synthesis in bacteria: Analysis of the Bates/Kleckner
      licensing/initiation-mass model for cell cycle control.
AB  - Bates and Kleckner have recently proposed that bacterial cell division is a
      licensing agent for a subsequent initiation of DNA replication. They also propose
      that initiation mass for DNA replication is not constant. These two proposals do
      not take into account older data showing that initiation of DNA replication can
      occur prior to the division event. This critical analysis is derived from
      measurements of DNA replication during the division cycle in cells growing at
      different, and more rapid, growth rates. Furthermore, mutants impaired in
      division can initiate DNA synthesis. The data presented by Bates and Kleckner do
      not support the proposal that initiation mass is variable, and the proposed
      pattern of DNA replication during the division cycle of the K12 cells analysed is
      not consistent with prior data on the pattern of DNA replication during the
      division cycle.

PMID- 17020575
TI  - Secretion by numbers: Protein traffic in prokaryotes.
AB  - Almost all aspects of protein traffic in bacteria were covered at the ASM-FEMS
      meeting on the topic in Iraklio, Crete in May 2006. The studies presented ranged
      from mechanistic analysis of specific events leading proteins to their final
      destinations to the physiological roles of the targeted proteins. Among the
      highlights from the meeting that are reviewed here are the molecular dynamics of
      SecA protein, membrane protein insertion, type III secretion needles and
      chaperones, type IV secretion, the two partner and autosecretion systems, the
      'secretion competent state', and the recently discovered type VI secretion
      system.

PMID- 17020576
TI  - The Escherichia coli chromosome is organized with the left and right chromosome
      arms in separate cell halves.
AB  - We have developed a system for the simultaneous labelling of two specific
      chromosomal sites using two different fluorescent ParB/parS systems. Using this,
      we demonstrate that the two chromosome arms are spatially arranged in newborn
      cells such that markers on the left arm of the chromosome lie in one half of the
      cell and markers on the right arm of the chromosome lie in the opposite half.
      This is achieved by reorganizing the chromosome arms of the two nucleoids in pre
      division cells relative to the cell quarters. The spatial reorganization of the
      chromosome arms ensures that the two replication forks remain in opposite halves
      of the cell during replication. The relative orientation of the two reorganized
      nucleoids in pre-division cells is not random. Approximately 80% of dividing
      cells have their nucleoids oriented in a tandem configuration.

PMID- 17020577
TI  - Investigating the role of calcium/calmodulin-dependent protein kinases in
      Stagonospora nodorum.
AB  - Three genes encoding different Ca2+/calmodulin-dependent protein kinases have
      been characterized in the wheat phytopathogenic fungus Stagonospora nodorum. The
      kinases were identified from the S. nodorum genome sequence on the basis of
      sequence homology to known Ca2+/calmodulin-dependent protein kinases. Expression
      analysis determined that each of the kinases was expressed during growth in vitro
      and also during infection. The onset of sporulation triggered increased
      transcript levels of each of the kinases, particularly CpkA where an 11-fold
      increase in expression was observed during sporulation in planta. The role of the
      kinases was further determined via a reverse genetics approach. The disruption of
      CpkA affected vegetative growth in vitro and also sporulation. The cpkA strains
      produced 20-fold less spores on complex media and were unable to sporulate on
      defined minimal media. Infection assays showed that CpkA was not required for
      lesion development but was essential for sporulation at the completion of the
      infection cycle. Microscopic analysis revealed that the disruption of CpkA
      resulted in Stagonospora nodorum being unable to differentiate the mycelial knot
      into immature pycnidia during sporulation. A metabolite analysis of infected
      leaves during sporulation excluded the possible involvement of mannitol, a
      compound previously shown to be involved in the sporulation of Stagonospora
      nodorum. The disruption of CpkB did not effect growth in vitro or pathogenicity.
      Stagonospora nodorum strains lacking CpkC appeared unaffected during growth in
      planta but showed delayed lesion development and sporulation during infection.

PMID- 17020578
TI  - The Escherichia coli UvrD helicase is essential for Tus removal during
      recombination-dependent replication restart from Ter sites.
AB  - Blocking replication forks in the Escherichia coli chromosome by ectopic Ter
      sites renders the RecBCD pathway of homologous recombination and SOS induction
      essential for viability. In this work, we show that the E. coli helicase II
      (UvrD) is also essential for the growth of cells where replication forks are
      arrested at ectopic Ter sites. We propose that UvrD is required for Tus removal
      from Ter sites. The viability of a SOS non-inducible Ter-blocked strain is fully
      restored by the expression of the two SOS-induced proteins UvrD and RecA at high
      level, indicating that these are the only two SOS-induced proteins required for
      replication across Ter/Tus complexes. Several observations suggest that UvrD acts
      in concert with homologous recombination and we propose that UvrD is associated
      with recombination-initiated replication forks and that it removes Tus when a
      PriA-dependent, restarted replication fork goes across the Ter/Tus complex.
      Finally, expression of the UvrD homologue from Bacilus subtilis PcrA restores the
      growth of uvrD-deficient Ter-blocked cells, indicating that the capacity to
      dislodge Tus is conserved in this distant bacterial species.

PMID- 17020579
TI  - Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes
      and can stabilize plasmids.
AB  - Vibrio cholerae codes for 13 toxin-antitoxin (TA) loci all located within the
      superintegron on chromosome II. We show here that the two higBA TA loci of V.
      cholerae encode functional toxins, HigB-1 and HigB-2, whose ectopic expression
      inhibits cell growth of Escherichia coli, and functional antitoxins, HigA-1 and
      HigA-2, which counteract the toxicity of the cognate toxins. Three hours of
      ectopic expression of the HigB toxins resulted in bacteriostasis without any
      detectable loss of cell viability. The HigB toxins inhibited translation by
      cleavage of mRNA. Efficient mRNA cleavage occurred preferentially within the
      translated part of a model mRNA and only when the mRNA was translatable. Promoter
      analysis in V. cholerae and E. coli showed that the two higBA loci are both
      transcribed into bi-cistronic mRNAs and that the higBA-2 mRNA is leaderless.
      Transcription of the two higBA loci was strongly induced by amino acid (aa)
      starvation in V. cholerae and E. coli, indicating that the regulatory mechanisms
      of transcriptional induction are conserved across the two species. Both higBA
      loci stabilized a test-plasmid very efficiently in E. coli, raising the
      possibility that the loci contribute to maintain genetic stability of the V.
      cholerae superintegron. Based on these results we discuss the possible biological
      functions of the TA loci of V. cholerae.

PMID- 17020580
TI  - Cell wall-inhibitory antibiotics activate the alginate biosynthesis operon in
      Pseudomonas aeruginosa: Roles of sigma (AlgT) and the AlgW and Prc proteases.
AB  - A bioassay was developed to identify stimuli that promote the transcriptional
      induction of the algD operon for alginate biosynthesis in Pseudomonas aeruginosa.
      Strain PAO1 carried the algD promoter fused to a chloramphenicol acetyl
      transferase cartridge (PalgD-cat), and > 50 compounds were tested for promoting
      chloramphenicol resistance. Most compounds showing PalgD-cat induction were cell
      wall-active antibiotics that blocked peptidoglycan synthesis. PalgD-cat induction
      was blocked by mutations in the genes for sigma22 (algT/algU) or regulators AlgB
      and AlgR. Anti-sigma factor MucA was the primary regulator of sigma22 activity. A
      transcriptome analysis using microarrays verified that the algD operon undergoes
      high induction by D-cycloserine. A similar sigma(E)-RseAB complex in Escherichia
      coli responds to envelope stress, which requires DegS protease in a regulated
      intramembrane proteolysis (RIP) cascade to derepress the sigma. Mutant phenotypic
      studies in P. aeruginosa showed that AlgW (PA4446) is likely to be the DegS
      functional homologue. A mutation in algW resulted in a complete lack of PalgD-cat
      induction by D-cycloserine. Overexpression of algW in PAO1 resulted in a mucoid
      phenotype and alginate production, even in the absence of cell wall stress,
      suggesting that AlgW protease plays a role in sigma22 activation. In addition, a
      mutation in gene PA3257 (prc), encoding a Prc-like protease, resulted in poor
      induction of PalgD-cat by D-cycloserine, suggesting that it also plays a role in
      the response to cell wall stress.

PMID- 17020581
TI  - Formation of active inclusion bodies in the periplasm of Escherichia coli.
AB  - To examine the relationship between folding and aggregation in the periplasm of
      Escherichia coli, we have analysed the cellular fates of exported proteins fused
      to either the wild-type maltose-binding protein (MalE) or the aggregation-prone
      variant MalE31. The propensity of fusion proteins to aggregate in the periplasm
      was determined by the intrinsic folding characteristics of the upstream protein.
      When beta-lactamase or alkaline phosphatase was linked to the C-terminus of
      MalE31, the resultant fusion proteins accumulated in an insoluble form, but
      retained their catalytic activity. In addition, these protein aggregates induced
      an extracytoplasmic stress response, similar to unfused MalE31. However, using a
      fluorescent substrate, we found that alkaline phosphatase activity was present
      inside periplasmic aggregates. These results suggest that periplasmic inclusion
      body formation may result in intermolecular interactions between participating
      proteins without loss of function of the fused enzymes.

PMID- 17020582
TI  - Role of Gal11, a component of the RNA polymerase II mediator in stress-induced
      hyperphosphorylation of Msn2 in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the Msn2 transcription factor is a key
      element in mediating the environmental stress response (ESR), leading to the
      induction of 100-200 genes through the cis-acting Stress Response Element (STRE)
      in response to various physico-chemical stresses and nutritional variations. This
      activation is accompanied by a stress-induced hyperphosphorylation of Msn2. By a
      systematic screening we identified two proteins essential in this process: (i)
      the cyclin-dependent Ssn3/Srb10 protein kinase, part of a module of the RNA
      polymerase II mediator, which has already been shown to be involved in
      hyperphosphorylation and degradation of Msn2 upon stress, and (ii) Gal11, a
      component of the mediator. In a gal11 mutant, stress-induced hyperphosphorylation
      of Msn2 is abolished, stress-induced transcription of Msn2-dependent genes is
      decreased and Msn2 degradation is impaired. Rgr1, another component of the
      mediator, is also critical for this hyperphosphorylation, indicating that the
      integrity of the mediator is required for this process. Moreover the
      transactivating region of Msn2 interacts in vitro with the N-terminal domain of
      Gal11. These results point out the role of the mediator, especially its Gal11
      subunit, in the hyperphosphorylation and degradation of Msn2 during stress
      response.

PMID- 17020583
TI  - Induction of expression of hfq by DksA is essential for Shigella flexneri
      virulence.
AB  - Hfq plays an important role in cellular physiology by regulating the expression
      of several genes. Hfq synthesis in Escherichia coli is subject to auto-repression
      at translational level. Studies with Shigella flexneri show that hfq
      transcription is regulated by a pleiotropic regulator, DksA. Comparison of gene
      expression profiles of wild type and dksA mutant S. flexneri determined that hfq
      expression was reduced in the dksA mutant. As DksA is required for stress
      resistance and plaque formation in cultured cell monolayers, a measure of
      virulence, we assessed the role of Hfq in the dksA virulence phenotype.
      Expression of hfq in the dksA mutant restored plaque formation, and an hfq mutant
      failed to form plaques. Thus, DksA plays a role in regulating hfq gene expression
      and this regulation is important for S. flexneri virulence. In an in vitro
      transcription assay, addition of DksA increased transcription of hfq and this
      effect was greatest with one of the known hfq promoters. Addition of ppGpp, a
      stringent response molecule, along with DksA in the in vitro transcription assay
      resulted in a further increase in transcription of hfq, indicating that DksA is
      required for maximal transcription of hfq during both exponential and stringent
      response growth conditions.

PMID- 17020584
TI  - Opposing signals differentially regulate transcript stability in Aspergillus
      nidulans.
AB  - A good model for gene regulation, requiring the organism to monitor a complex and
      changing environment and respond in a precise and rapid way, is nitrogen
      metabolism in Aspergillus nidulans. This involves co-ordinated expression of
      hundreds of genes, many dependent on the transcription factor AreA, which
      monitors the nitrogen state of the cell. AreA activity is in part modulated by
      differential degradation of its transcript in response to intracellular
      glutamine. Here we report that glutamine triggers synchronized degradation of a
      large subset of transcripts involved in nitrogen metabolism. Among these are all
      four genes involved in the assimilation of nitrate. Significantly, we show that
      two of these transcripts, niaD and niiA, are stabilized by intracellular nitrate,
      directly reinforcing transcriptional regulation. Glutamine-signalled degradation
      and the nitrate-dependent stabilization of the niaD transcript are effected at
      the level of deadenylation and are dependent on its 3' UTR. When glutamine and
      nitrate are both present, nitrate stabilization is predominant, ensuring that
      nitrate and the toxic intermediate nitrite are removed from the cell. Regulated
      transcript stability is therefore an integral part of the adaptive response. This
      represents the first example of distinct physiological signals competing to
      differentially regulate transcripts at the level of deadenylation.

PMID- 17020585
TI  - The small untranslated RNA SR1 from the Bacillus subtilis genome is involved in
      the regulation of arginine catabolism.
AB  - Whereas about 70 small non-coding RNAs have been found in the Escherichia coli
      genome, relatively little is known about regulatory RNAs from Gram-positive
      bacteria. Here, we demonstrate that the recently identified small untranslated
      RNA SR1 from the Bacillus subtilis genome is a regulatory RNA involved in fine
      tuning of arginine catabolism. 2D protein gel electrophoresis indicated three
      possible SR1 targets that are regulated by the transcriptional activator AhrC,
      which was shown to be the primary target of SR1. In vitro pairing studies and an
      in vivo reporter gene test demonstrated a specific interaction between SR1 and
      ahrC mRNA. This interaction did not lead to degradation of ahrC mRNA, but
      inhibited translation at a post-initiation stage. Our data show that the Hfq
      chaperone was not required for the stabilization of SR1 in vivo. The amount of
      SR1 was increased upon addition of l-arginine and l-ornithine, but not l
      citrulline or l-proline.

PMID- 17020586
TI  - The HD-GYP domain of RpfG mediates a direct linkage between the Rpf quorum
      sensing pathway and a subset of diguanylate cyclase proteins in the phytopathogen
      Xanthomonas axonopodis pv citri.
AB  - Bacteria use extracellular levels of small diffusible autoinducers to estimate
      local cell-density (quorum-sensing) and to regulate complex physiological
      processes. The quorum-sensing signal transduction pathway of Xanthomonas spp.
      phytopathogens has special features that distinguish it from that of other
      pathogens. This pathway consists of RpfF, necessary for the production of the
      unique autoinducer 'diffusible signalling factor' (DSF), and RpfC and RpfG, a two
      component system necessary for the DSF-dependent production of extracellular
      pathogenicity factors and cellular dispersion. Yeast two-hybrid and direct in
      vitro assays were used to identify interactions involving the Rpf group of
      proteins. We show that RpfC, a protein consisting of N-terminal transmembrane,
      histidine kinase, response-regulator and C-terminal histidine phosphotransfer
      domains interacts with both RpfG, a protein consisting of an N-terminal response
      regulator domain and a C-terminal HD-GYP domain, and with RpfF. We also show that
      RpfC interacts with the only known homologue of 'conditioned medium factor',
      which is involved in quorum-sensing in Dictyostelium discoideum under conditions
      of nutritional stress. Furthermore, RpfCG is shown to interact with a second two
      component system made up of NtrB and NtrC homologues. Finally we show that the
      recently characterized HD-GYP phosphodiesterase domain of RpfG interacts directly
      with diguanylate cyclase GGDEF domain-containing proteins coded by the
      Xanthomonas axonopodis pv. citri genome, which in other bacteria produce cyclic
      diGMP, an important second messenger involved in the regulation of complex
      bacterial processes including biofilm production, virulence and motility. These
      results demonstrate a direct physical linkage between quorum-sensing and cyclic
      diGMP signalling pathways in bacteria.

PMID- 17020587
TI  - YpdC determines site-1 degradation in regulated intramembrane proteolysis of the
      RsiW anti-sigma factor of Bacillus subtilis.
AB  - Genes of Bacillus subtilis controlled by the alternative extracytoplasmic
      function family sigma factor sigmaW constitute an antibiosis regulon. Its
      activity is modulated by RsiW, a transmembrane anti-sigma factor that sequesters
      and inactivates sigmaW. Upon a stress signal, RsiW is degraded by a mechanism of
      regulated intramembrane proteolysis. To identify genes which influence RsiW
      degradation, a transposon screen with a reporter fusion of the green fluorescent
      protein to RsiW was performed. Among several gene loci identified, the ypdC
      (prsW) gene displayed a strong effect on RsiW stability. In a ypdC null mutant,
      induction of sigmaW-controlled genes is abolished and site-1 proteolysis of RsiW
      is completely blocked. Transcriptional analysis revealed that ypdC is a
      monocistronic gene, and the defect of sigmaW induction of the null mutant was
      complemented by ectopically integrated ypdC under xylose control. Orthologues of
      YpdC can be found in a variety of different bacteria. Its membrane topology was
      analysed by alkaline phosphatase fusions, revealing that YpdC contains five
      transmembrane segments and two larger extracytoplasmic loops. In the first loop,
      two invariantly conserved glutamate residues can be found. In an Escherichia coli
      system, the cloned ypdC is the only determinant of efficient degradation of RsiW;
      however, YpdC does not display plain similarities to known proteases, suggesting
      that it either controls the activity of site-1 proteolysis of RsiW or represents
      a new type of protease.

PMID- 17020588
TI  - Regulated intramembrane proteolysis of FtsL protein and the control of cell
      division in Bacillus subtilis.
AB  - The small bitopic division protein FtsL is an essential part of the division
      machinery (divisome) in most eubacteria. In Bacillus subtilis FtsL is a highly
      unstable protein and the turnover has been implicated in regulation of division
      in response to DNA damage. N-terminal deletions and a domain swap experiment
      identified the short cytoplasmic domain of FtsL as being required for
      instability. We then identified a zinc metalloprotease, YluC, required for
      turnover, and likely sequence motifs involved in substrate recognition. YluC
      belongs to the site-2-protease (S2P) family of proteases involved in regulated
      intramembrane proteolysis (RIP), which plays a role in diverse regulatory
      phenomena from bacteria to man. The yluC mutant, and strains with N-terminal
      truncations of ftsL have a short cell phenotype, indicating that that FtsL is
      normally rate-limiting for division. Coexpression experiments of FtsL and YluC in
      Escherichia coli corroborated a model in which FtsL is directly cleaved by the
      membrane metalloprotease. The results shed new light on the regulation of cell
      division in B. subtilis and identify a novel class of targets for RIP.

PMID- 17020589
TI  - The carrier Msn5p/Kap142p promotes nuclear export of the hsp70 Ssa4p and
      relocates in response to stress.
AB  - Cytoplasmic hsp70s like yeast Ssa4p shuttle between nucleus and cytoplasm under
      normal growth conditions but accumulate in nuclei upon stress. This nuclear
      accumulation is only transient, and Ssa4p relocates to the cytoplasm when cells
      recover. We show here that Ssa4p nuclear export is independent of Xpol/Crm1 and
      identify the importin-beta family member Msn5p/Kap142p as the exporter for Ssa4p.
      In growing cells and in vitro, Msn5p and Ssa4p generate genuine export complexes
      that require Ran/Gsp1p-GTP. Furthermore, nucleoporin Nup82p, which plays a role
      in Msn5p-mediated transport, is necessary for efficient export of Ssa4p. In
      living cells, stress not only regulates Ssa4p localization, but also controls the
      distribution of Msn5p. Msn5p is concentrated in nuclei of unstressed cells, but
      appears in the cytoplasm upon exposure to ethanol, heat, starvation or severe
      oxidative stress. In addition, growth on non-fermentable carbon sources relocates
      a portion of Msn5p to the cytoplasm and leads to a partial nuclear accumulation
      of Ssa4p. Taken together, growth and stress conditions that localize the
      transporter Msn5p to the cytoplasm also induce the nuclear accumulation of its
      cargo Ssa4p.

PMID- 17020590
TI  - Molecular orchestration of the hepatic circadian symphony.
AB  - The circadian clock determines the rhythmic expression of many different genes
      throughout a 24-hour period. A recent study investigating the circadian
      regulation of liver proteins reveals multiple levels of regulation, including
      transcriptional, post-transcriptional and post-translational mechanisms.

PMID- 17020591
TI  - Regulatory RNAs and the demise of 'junk' DNA.

PMID- 17020593
TI  - Genomics and the bacterial species problem.
AB  - Whether or not bacteria have species is a perennially vexatious question. Given
      what we now know about variation among bacterial genomes, we argue that there is
      no intrinsic reason why the processes driving diversification and adaptation must
      produce groups of individuals sufficiently coherent in their genetic and
      phenotypic properties to merit the designation 'species'--although sometimes they
      might.

PMID- 17020594
TI  - AIP or ARDS? Not just semantics.

PMID- 17020595
TI  - Ethics roundtable debate: patients and surrogates want 'everything done'--what
      does 'everything' mean?
AB  - Highly complex and specialized care plans sometimes overwhelm the comprehension
      of patients and families. Many optimistic surrogates of critically ill patients
      err on the side of desiring that everything be done but with a nebulous idea of
      what 'everything' entails. Physicians must work closely to educate surrogates as
      to the benefits versus the risks of treatment. Our roundtable experts ponder the
      question of whether providers possess the authority to interpret unilaterally the
      nature of requests for everything.

PMID- 17020597
TI  - Organ donation after circulatory death: the forgotten donor?
AB  - Donation after circulatory death (DCD) can be performed on neurologically intact
      donors who do not fulfill neurologic or brain death criteria before circulatory
      arrest. This commentary focuses on the most controversial donor-related issues
      anticipated from mandatory implementation of DCD for imminent or cardiac death in
      hospitals across the USA. We conducted a nonstructured review of selected
      publications and websites for data extraction and synthesis. The recommended 5
      min of circulatory arrest does not universally fulfill the dead donor rule when
      applied to otherwise neurologically intact donors. Scientific evidence from
      extracorporeal perfusion in circulatory arrest suggests that the procurement
      process itself can be the event causing irreversibility in DCD. Legislative
      abandonment of the dead donor rule to permit the recovery of transplantable
      organs is necessary in the absence of an adequate scientific foundation for DCD
      practice. The designation of organ procurement organizations or affiliates to
      obtain organ donation consent introduces self-serving bias and conflicts of
      interest that interfere with true informed consent. It is important that donors
      and their families are not denied a 'good death', and the impact of DCD on
      quality of end-of-life care has not been satisfactorily addressed to achieve
      this.

PMID- 17020596
TI  - Arrestins: ubiquitous regulators of cellular signaling pathways.
AB  - In vertebrates, the arrestins are a family of four proteins that regulate the
      signaling and trafficking of hundreds of different G-protein-coupled receptors
      (GPCRs). Arrestin homologs are also found in insects, protochordates and
      nematodes. Fungi and protists have related proteins but do not have true
      arrestins. Structural information is available only for free (unbound) vertebrate
      arrestins, and shows that the conserved overall fold is elongated and composed of
      two domains, with the core of each domain consisting of a seven-stranded beta
      sandwich. Two main intramolecular interactions keep the two domains in the
      correct relative orientation, but both of these interactions are destabilized in
      the process of receptor binding, suggesting that the conformation of bound
      arrestin is quite different. As well as binding to hundreds of GPCR subtypes,
      arrestins interact with other classes of membrane receptors and more than 20
      surprisingly diverse types of soluble signaling protein. Arrestins thus serve as
      ubiquitous signaling regulators in the cytoplasm and nucleus.

PMID- 17020598
TI  - Malaria treatment failures after artemisinin-based therapy in three expatriates:
      could improved manufacturer information help to decrease the risk of treatment
      failure?
AB  - BACKGROUND: Artemisinin-containing therapies are highly effective against
      Plasmodium falciparum malaria. Insufficient numbers of tablets and inadequate
      package inserts result in sub-optimal dosing and possible treatment failure. This
      study reports the case of three, non-immune, expatriate workers with P.
      falciparum acquired in Africa, who failed to respond to artemisinin-based
      therapy. Sub-therapeutic dosing in accordance with the manufacturers'
      recommendations was the probable cause. METHOD: Manufacturers information and
      drug content included in twenty-five artemisinin-containing specialities were
      reviewed. RESULTS: A substantial number of manufacturers do not follow current
      WHO recommendations regarding treatment duration and doses. CONCLUSION: This
      study shows that drug packaging and their inserts should be improved.

PMID- 17020599
TI  - New PCR systems to confirm real-time PCR detection of Mycobacterium avium subsp.
      paratuberculosis.
AB  - BACKGROUND: Johne's disease, a serious chronic form of enteritis in ruminants, is
      caused by Mycobacterium avium subsp. paratuberculosis (MAP). As the organism is
      very slow-growing and fastidious, several PCR-based methods for detection have
      been developed, based mainly on the MAP-specific gene IS900. However, because
      this gene is similar to genes in other mycobacteria, there is a need for
      sensitive and reliable methods to confirm the presence of MAP. As described here,
      two new real-time PCR systems on the IS900 gene and one on the F57 gene were
      developed and carefully validated on 267 strains and 56 positive clinical faecal
      samples. RESULTS: Our confirmatory PCR systems on IS900 were found sensitive and
      specific, only yielding weak false positive reactions in one strain for each
      system. The PCR system on F57 did not elicit any false positives and was only
      slightly less sensitive than our primary IS900-system. DNA from both naturally
      infected and spiked faeces that tested positive with our primary system could be
      confirmed with all new systems, except one low-level infected sample that tested
      negative with the F57 system. CONCLUSION: We recommend using the newly
      constructed DH3 PCR system on the F57 gene as the primary confirmatory test for
      PCR positives, but should it fail due to its lower sensitivity, the DH1 and DH2
      PCR systems should be used.

PMID- 17020600
TI  - Early postoperative serum S100 beta levels predict ongoing brain damage after
      meningioma surgery: a prospective observational study.
AB  - INTRODUCTION: Elevated serum levels of S100beta, an astrocyte-derived protein,
      correlate with unfavourable neurological outcomes following cardiac surgery,
      neurotrauma, and resuscitation. This study evaluated whether pre-/postoperative
      serum S100beta levels correlate with unfavourable clinical and radiological
      findings in patients undergoing elective meningioma resection. METHODS: In 52
      consecutive patients admitted for meningioma surgery, serum S100beta levels were
      determined upon admission and immediately, 24 hours, and 48 hours after surgery.
      All patients underwent complete pre- and postoperative neurological examination
      and mini-mental state examination. Radiological evaluation included preoperative
      magnetic resonance imaging (MRI) and postoperative computed tomography. Tumour
      volume, brain edema, and bleeding volume were calculated using BrainSCAN
      software. RESULTS: Preoperative S100beta levels did not correlate with the tumour
      characteristics demonstrated by preoperative MRI (for example, tumour volume,
      edema volume, ventricular asymmetry, and/or midline shift). Preoperative serum
      S100beta levels (0.065 +/- 0.040 microg/l) were significantly lower than the
      levels measured immediately (0.138 +/- 0.081 microg/l), 24 hours (0.142 +/- 0.084
      microg/l), and 48 hours (0.155 +/- 0.119 microg/l) postoperatively (p < 0.0001).
      Significantly greater postcraniotomy S100beta levels were observed with prolonged
      surgery (p = 0.039), deterioration in the mini-mental state examination (p =
      0.005, 0.011, and 0.036 for pre versus immediate, 24 hours, and 48 hours
      postsurgery, respectively), and with postoperative brain computed tomography
      evidence of brain injury; bleeding was associated with higher serum S100beta
      levels at 24 and 48 hours after surgery (p = 0.046, 95% confidence interval [CI] 
      0.095 to -0.001 and p = 0.034, 95% CI -0.142 to -0.006, respectively) as was the
      presence of midline shift (p = 0.005, 95% CI -0.136 to -0.025 and p = 0.006, 95%
      CI -0.186 to -0.032, respectively). Edema was associated with higher serum
      S100beta levels immediately (p = 0.022, 95% CI -0.092 to -0.007) and at 48 hours
      after surgery (p = 0.017, 95% CI -0.142 to -0.026). The degree of elevation in
      S100beta levels at 24 and 48 hours after surgery also correlated with the
      severity of midline shift and edema. CONCLUSION: In patients with meningioma,
      serum S100beta levels perform poorly as an indicator of tumour characteristics
      but may suggest ongoing postcraniotomy injury. Serum S100beta levels may serve as
      a potentially useful early marker of postcraniotomy brain damage in patients
      undergoing elective meningioma resection.

PMID- 17020601
TI  - Elevated serum triglycerides is the strongest single indicator for the presence
      of metabolic syndrome in patients with type 2 diabetes.
AB  - BACKGROUND: Patients with diabetes already fulfill one diagnostic criterion for
      MS according to the existing classifications. Our aim was to identify one single
      clinical parameter, which could effectively predict the presence of MS in
      patients with type 2 diabetes. METHODS: We studied all patients with type 2
      diabetes who attended our Diabetes Outpatient Clinic during a three-month period.
      Waist circumference, blood pressure and serum lipids were measured. Establishment
      of MS diagnosis was based a) on National Cholesterol Education Program Adult
      Treatment Panel III (NCEP ATP III) criteria and b) on International Diabetes
      Federation (IDF) criteria. Receiver operating characteristic (ROC) analysis was
      applied in order to identify the clinical parameter with the highest predictive
      capability for MS. Among the 500 participating patients (231 males, 269 females),
      MS was diagnosed in 364 patients (72.8%) according to the NCEP ATP III criteria
      and in 408 patients (81.6%) according to the IDF criteria. RESULTS: For the NCEP
      ATP III classification, serum triglycerides (in the overall population), waist
      and HDL (in female population) demonstrated the highest predictive capability for
      MS (AUCs:0.786, 0.805 and 0.801, respectively). For the IDF classification, no
      single parameter reached an AUC > 0.800 in the overall population. In females,
      HDL displayed a satisfactory predictive capability for MS with an AUC which was
      significantly higher than the one in males (0.785 vs. 0.676, respectively, p <
      0.05). CONCLUSION: Elevated serum triglycerides strongly indicate the presence of
      MS in patients with type 2 diabetes. In female patients with type 2 diabetes,
      central obesity was the second stronger predictor of MS besides
      hypertriglyceridemia.

PMID- 17020602
TI  - Adaptive evolution of the spike gene of SARS coronavirus: changes in positively
      selected sites in different epidemic groups.
AB  - BACKGROUND: It is believed that animal-to-human transmission of severe acute
      respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak
      worldwide. The spike (S) protein is one of the best characterized proteins of
      SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and
      accomplishing interspecies transmission from animals to humans, suggesting that
      it may be the major target of selective pressure. However, the process of
      adaptive evolution of S protein and the exact positively selected sites
      associated with this process remain unknown. RESULTS: By investigating the
      adaptive evolution of S protein, we identified twelve amino acid sites (75, 239,
      244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under
      positive selective pressure. Based on phylogenetic tree and epidemiological
      investigation, SARS outbreak was divided into three epidemic groups: 02-04
      interspecies, 03-early-mid, and 03-late epidemic groups in the present study.
      Positive selection was detected in the first two groups, which represent the
      course of SARS-CoV interspecies transmission and of viral adaptation to human
      host, respectively. In contrast, purifying selection was detected in 03-late
      group. These indicate that S protein experiences variable positive selective
      pressures before reaching stabilization. A total of 25 sites in 02-04
      interspecies epidemic group and 16 sites in 03-early-mid epidemic group were
      identified under positive selection. The identified sites were different between
      these two groups except for site 239, which suggests that positively selected
      sites are changeable between groups. Moreover, it was showed that a larger
      proportion (24%) of positively selected sites was located in receptor-binding
      domain (RBD) than in heptad repeat (HR)1-HR2 region in 02-04 interspecies
      epidemic group (p = 0.0208), and a greater percentage (25%) of these sites
      occurred in HR1-HR2 region than in RBD in 03-early-mid epidemic group (p =
      0.0721). These suggest that functionally different domains of S protein may not
      experience same positive selection in each epidemic group. In addition, three
      specific replacements (F360S, T487S and L665S) were only found between 03-human
      SARS-CoVs and strains from 02-04 interspecies epidemic group, which reveals that
      selective sweep may also force the evolution of S genes before the jump of SARS
      CoVs into human hosts. Since certain residues at these positively selected sites
      are associated with receptor recognition and/or membrane fusion, they are likely
      to be the crucial residues for animal-to-human transmission of SARS-CoVs, and
      subsequent adaptation to human hosts. CONCLUSION: The variation of positive
      selective pressures and positively selected sites are likely to contribute to the
      adaptive evolution of S protein from animals to humans.

PMID- 17020603
TI  - Molecular phylogeny of the antiangiogenic and neurotrophic serpin, pigment
      epithelium derived factor in vertebrates.
AB  - BACKGROUND: Pigment epithelium derived factor (PEDF), a member of the serpin
      family, regulates cell proliferation, promotes survival of neurons, and blocks
      growth of new blood vessels in mammals. Defining the molecular phylogeny of PEDF
      by bioinformatic analysis is one approach to understanding the link between its
      gene structure and its function in these biological processes. RESULTS: From a
      comprehensive search of available DNA databases we identified a single PEDF gene
      in all vertebrate species examined. These included four mammalian and six non
      mammalian vertebrate species in which PEDF had not previously been described. A
      five gene cluster around PEDF was found in an approximate 100 kb region in
      mammals, birds, and amphibians. In ray-finned fish these genes are scattered over
      three chromosomes although only one PEDF gene was consistently found. The PEDF
      gene is absent in invertebrates including Drosophila melanogaster (D.
      melanogaster), Caenorhabditis elegans (C. elegans), and sea squirt (C.
      intestinalis). The PEDF gene is transcribed in all vertebrate phyla, suggesting
      it is biologically active throughout vertebrate evolution. The multiple actions
      of PEDF are likely conserved in evolution since it has the same gene structure
      across phyla, although the size of the gene ranges from 48.3 kb in X. tropicalis
      to 2.9 kb in fugu, with human PEDF at a size of 15.6 kb. A strong similarity in
      the proximal 200 bp of the PEDF promoter in mammals suggests the existence of a
      possible regulatory region across phyla. Using a non-synonymous/synonymous
      substitution rate ratio we show that mammalian and fish PEDFs have similar ratios
      of <0.13, reflecting a strong purifying selection of PEDF gene. A large number of
      repetitive transposable elements of the SINE and LINE class were found with
      random distribution in both the promoter and introns of mammalian PEDF.
      CONCLUSION: The PEDF gene first appears in vertebrates and our studies suggest
      that the regulation and biological actions of this gene are preserved across
      vertebrates. This comprehensive analysis of the PEDF gene across phyla provides
      new information that will aid further characterization of common functional
      motifs of this serpin in biological processes.

PMID- 17020604
TI  - Mortality and life expectancy of professional fire fighters in Hamburg, Germany:
      a cohort study 1950-2000.
AB  - BACKGROUND: The healthy worker effect may hide adverse health effects in
      hazardous jobs, especially those where physical fitness is required. Fire
      fighters may serve as a good example because they sometimes are severely exposed
      to hazardous substances while on the other hand their physical fitness and their
      strong health surveillance by far exceeds that of comparable persons from the
      general population. METHODS: To study this effect a historic cohort study was
      conducted to assess mortality and life expectancy of professional fire fighters
      of the City of Hamburg, Germany. Fire departments and trade unions questioned the
      validity of existing studies from outside Germany because of specific differences
      in the professional career. No mortality study had been conducted so far in
      Germany and only few in Europe. Information on all active and retired fire
      fighters was extracted from personnel records. To assure completeness of data the
      cohort was restricted to all fire fighters being active on January 1, 1950 or
      later. Follow up of the cohort ended on June 30th 2000. Vital status was assessed
      by personnel records, pension fund records and the German residence registries.
      Mortality of fire fighters was compared to mortality of the Hamburg and German
      male population by means of standardized mortality ratios. Life expectancy was
      calculated using life table analysis. Multivariate proportional hazard models
      were used to assess the effect of seniority, time from first employment, and
      other occupational characteristics on mortality. RESULTS: The cohort consists of
      4640 fire fighters accumulating 111,796 person years. Vital status could be
      determined for 98.2% of the cohort. By the end of follow up 1052 person were
      deceased. Standardized Mortality Ratio (SMR) for the total cohort was 0.79 (95%
      CI, 0.74-0.84) compared to Hamburg reference data and 0.78 (95% CI, 0.74-0.83)
      compared to National German reference data. Conditional life expectancy of a 30
      year old fire fighter was 45.3 years as compared to 42.9 year of a German male in
      normal population. Job tasks, rank status and early retirement negatively
      influenced mortality. For fire fighters with comparably short duration of
      employment the mortality advantage diminished with longer time since first
      employment. SMR of persons who retired early was 1.25 (95% CI, 1.13-1.60) in
      reference to the general German population and the SMR of 1.71 (1.18-2.50) in the
      multivariate regression model. CONCLUSION: A strong healthy worker effect was
      observed for the cohort, which diminished with longer time since first employment
      for fire fighters with shorter duration of employment, as expected. The negative
      effects on mortality of job tasks, rank status and in particular early retirement
      indicate the presence of undetermined and specific risks related to occupational
      hazards of fire fighters.

PMID- 17020605
TI  - Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs
      of DAF-2/insulin-like signaling.
AB  - BACKGROUND: In the nematode, Caenorhabditis elegans, a conserved insulin-like
      signaling pathway controls larval development, stress resistance and adult
      lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3
      kinases (PI3K) comprises the major known effector pathway downstream of the
      insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB
      kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation
      of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF
      16 to direct dauer larval arrest and promote long lifespan in adult animals. In
      order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we
      conducted a genetic screen for mutations that suppress the constitutive dauer
      arrest phenotype of age-1(mg109) animals. RESULTS: This report describes
      mutations recovered in a screen for suppressors of the constitutive dauer arrest
      (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf
      16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1,
      encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation,
      mg227, located on chromosome X, did not correspond to any known dauer genes,
      suggesting that mg227 may represent a new component of the insulin pathway.
      Genetic epistasis analysis by RNAi showed that reproductive development in age
      1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly,
      reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on
      akt-1. However, reproductive development in age-1(mg109); mg227 animals required
      only akt-1, and pdk-1 activity was dispensable in this background. Interestingly,
      while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long
      lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect
      lifespan or stress resistance, while both daf-16 alleles fully suppressed these
      phenotypes. CONCLUSION: A screen for suppressors of PI3K mutant phenotypes
      identified activating mutations in two known pathway components, providing
      insights into their regulation. In particular, the interdependence of akt-1 and
      pdk-1, even in activated forms, supports the existence of AGE-1-independent
      pathways for these phospholipid-dependent kinases. Phenotypic analysis of these
      alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable
      in these mutants.

PMID- 17020606
TI  - The PedsQL Present Functioning Visual Analogue Scales: preliminary reliability
      and validity.
AB  - BACKGROUND: The PedsQL Present Functioning Visual Analogue Scales (PedsQL VAS)
      were designed as an ecological momentary assessment (EMA) instrument to rapidly
      measure present or at-the-moment functioning in children and adolescents. The
      PedsQL VAS assess child self-report and parent-proxy report of anxiety, sadness,
      anger, worry, fatigue, and pain utilizing six developmentally appropriate visual
      analogue scales based on the well-established Varni/Thompson Pediatric Pain
      Questionnaire (PPQ) Pain Intensity VAS format. METHODS: The six-item PedsQL VAS
      was administered to 70 pediatric patients ages 5-17 and their parents upon
      admittance to the hospital environment (Time 1: T1) and again two hours later
      (Time 2: T2). It was hypothesized that the PedsQL VAS Emotional Distress Summary
      Score (anxiety, sadness, anger, worry) and the fatigue VAS would demonstrate
      moderate to large effect size correlations with the PPQ Pain Intensity VAS, and
      that patient" parent concordance would increase over time. RESULTS: Test-retest
      reliability was demonstrated from T1 to T2 in the large effect size range.
      Internal consistency reliability was demonstrated for the PedsQL VAS Total
      Symptom Score (patient self-report: T1 alpha = .72, T2 alpha = .80; parent proxy
      report: T1 alpha = .80, T2 alpha = .84) and Emotional Distress Summary Score
      (patient self-report: T1 alpha = .74, T2 alpha = .73; parent proxy-report: T1
      alpha = .76, T2 alpha = .81). As hypothesized, the Emotional Distress Summary
      Score and Fatigue VAS were significantly correlated with the PPQ Pain VAS in the
      medium to large effect size range, and patient and parent concordance increased
      from T1 to T2. CONCLUSION: The results demonstrate preliminary test-retest and
      internal consistency reliability and construct validity of the PedsQL Present
      Functioning VAS instrument for both pediatric patient self-report and parent
      proxy-report. Further field testing is required to extend these initial findings
      to other ecologically relevant pediatric environments.

PMID- 17020607
TI  - Detecting local establishment strategies of wild cherry (Prunus avium L.).
AB  - BACKGROUND: P. avium, a pioneer tree species that colonizes early forest
      successional stages, is assumed to require an effective strategy allowing stably
      repeatable rounds of local establishment, dispersal and local extinction.
      Consequently, the early replacement of cherry by climax tree species makes the
      establishment of several local generations very unlikely, especially in central
      European continuous cover forests. This has to be seen in connection with the
      mixed reproduction system involving asexual reproduction as a complementary
      adaptational strategy. Tests of the local establishment of wild cherry must
      therefore consider the possibility of first generation establishment via seedling
      recruitment potentially followed by an asexual generation (root suckering).
      Successful establishment can therefore be determined only among adult individuals
      with the option of detecting vegetative reproduction at these stages. To test the
      implied suggestion about local establishment strategies of wild cherry, nuclear
      microsatellites were used to analyse patterns of asexual propagation among adult
      stages that have been subjected to one of two major types of forest management.
      These management types, the historical "coppice with standards system" (CWS) and
      the "high forest system" (HFS), can be reasonably assumed to have affected the
      reproduction system of P. avium. RESULTS: Clear differences were found in the
      reproduction pattern between two stands representing the two forest management
      types: 1) Clonal propagation is observed in both management systems, but with a
      distinctly higher frequency in the CWS. Hence, sexual recruitment as a first
      local generation is followed by a second asexual generation in both, whereas in
      the CWS there is evidence for an additional clonal generation. 2) The estimation
      of amounts of clonal reproduction critically depends on the assumptions about
      multilocus gene associations. This is revealed by the application of newly
      developed methods of quantifying gene associations. 3) Haplotype diversities are
      higher in the CWS and found to be associated with a large degree of
      heterozygosity for the second largest clonal group. 4) Seed set was sparse over
      the last eight years of observation in the CWS stand. CONCLUSION: This study
      provides useful guidelines for more comprehensive investigations, particularly on
      the interrelationships between degrees of cloning and capacity of sexual
      reproduction, amounts of multilocus gene associations, effects of heterozygosity
      on cloning success, and sustainability of different forest management types.

PMID- 17020609
TI  - Bilateral spontaneous hemotympanum: case report.
AB  - BACKGROUND: The most common causes of hemotympanum are therapeutic nasal packing,
      epistaxis, blood disorders and blunt trauma to the head. Hemotympanum is
      characterized as idiopathic, when it is detected in the presence of chronic
      otitis media. A rare case of spontaneous bilateral hemotympanum in a patient
      treated with anticoagulants is presented herein. CASE PRESENTATION: A 72-year-old
      male presented with acute deterioration of hearing. In the patient's medical
      history aortic valve replacement 1 year before presentation was reported. Since
      then he had been administered regularly coumarinic anticoagulants, with INR
      levels maintained between 3.4 and 4.0. Otoscopy revealed the presence of
      bilateral hemotympanum. The audiogram showed symmetrical moderately severe mixed
      hearing loss bilaterally, with the conductive component predominating.
      Tympanograms were flat bilaterally with absent acoustic reflexes. A computerized
      tomography scan showed the presence of fluid in the mastoid and middle ear
      bilaterally. Treatment was conservative and consisted of a 10-day course of
      antibiotics, anticongestants and temporary interruption of the anticoagulant
      therapy. After 3 weeks, normal tympanic membranes were found and hearing had
      returned to previous levels. CONCLUSION: Anticoagulant intake should be included
      in the differential diagnosis of hemotympanum, because its detection and
      appropriate treatment may lead to resolution of the disorder.

PMID- 17020608
TI  - Complete plastid genome sequences of Drimys, Liriodendron, and Piper:
      implications for the phylogenetic relationships of magnoliids.
AB  - BACKGROUND: The magnoliids with four orders, 19 families, and 8,500 species
      represent one of the largest clades of early diverging angiosperms. Although
      several recent angiosperm phylogenetic analyses supported the monophyly of
      magnoliids and suggested relationships among the orders, the limited number of
      genes examined resulted in only weak support, and these issues remain
      controversial. Furthermore, considerable incongruence resulted in phylogenetic
      reconstructions supporting three different sets of relationships among magnoliids
      and the two large angiosperm clades, monocots and eudicots. We sequenced the
      plastid genomes of three magnoliids, Drimys (Canellales), Liriodendron
      (Magnoliales), and Piper (Piperales), and used these data in combination with 32
      other angiosperm plastid genomes to assess phylogenetic relationships among
      magnoliids and to examine patterns of variation of GC content. RESULTS: The
      Drimys, Liriodendron, and Piper plastid genomes are very similar in size at
      160,604, 159,886 bp, and 160,624 bp, respectively. Gene content and order are
      nearly identical to many other unrearranged angiosperm plastid genomes, including
      Calycanthus, the other published magnoliid genome. Overall GC content ranges from
      34-39%, and coding regions have a substantially higher GC content than non-coding
      regions. Among protein-coding genes, GC content varies by codon position with 1st
      codon > 2nd codon > 3rd codon, and it varies by functional group with
      photosynthetic genes having the highest percentage and NADH genes the lowest.
      Phylogenetic analyses using parsimony and likelihood methods and sequences of 61
      protein-coding genes provided strong support for the monophyly of magnoliids and
      two strongly supported groups were identified, the Canellales/Piperales and the
      Laurales/Magnoliales. Strong support is reported for monocots and eudicots as
      sister clades with magnoliids diverging before the monocot-eudicot split. The
      trees also provided moderate or strong support for the position of Amborella as
      sister to a clade including all other angiosperms. CONCLUSION: Evolutionary
      comparisons of three new magnoliid plastid genome sequences, combined with other
      published angiosperm genomes, confirm that GC content is unevenly distributed
      across the genome by location, codon position, and functional group. Furthermore,
      phylogenetic analyses provide the strongest support so far for the hypothesis
      that the magnoliids are sister to a large clade that includes both monocots and
      eudicots.

PMID- 17020610
TI  - Metabolic changes after polytrauma: an imperative for early nutritional support.
AB  - Major trauma induces marked metabolic changes which contribute to the systemic
      immune suppression in severely injured patients and increase the risk of
      infection and posttraumatic organ failure. The hypercatabolic state of polytrauma
      patients must be recognized early and treated by an appropriate nutritional
      management in order to avoid late complications. Clinical studies in recent years
      have supported the concept of "immunonutrition" for severely injured patients,
      which takes into account the supplementation of Omega-3 fatty acids and essential
      aminoacids, such as glutamine. Yet many aspects of the nutritional strategies for
      polytrauma patients remain controversial, including the exact timing, caloric and
      protein amount of nutrition, choice of enteral versus parenteral route, and
      duration. The present review will provide an outline of the pathophysiological
      metabolic changes after major trauma that endorse the current basis for early
      immunonutrition of polytrauma patients.

PMID- 17020612
TI  - Ethnomedicinal plants used by the people of Manang district, central Nepal.
AB  - BACKGROUND: The district of Manang (2000 - 6000 m) is located in the Central
      Himalayas, Nepal. The majority of local inhabitants of the area are Gurungs, of
      Tibetan origin. The remoteness of the region has resulted in continued use of
      plants as medicine in an area where the ethnobotany has sparsely been documented.
      METHODS: Interviews were conducted with amchi (Tibetan medicinal practitioners),
      local healers (including priests locally known as 'lamas'), plant traders, and
      knowledgeable villagers (including herders) regarding local plant names and their
      medicinal uses during several field visits (2002-2005). When convenient to the
      locals, a jungle or forest walk was done with the healers, allowing for both
      plant collection and detailed information gathering. RESULTS: This present
      research documented 91 ethnomedicinal plant species, belonging to 40 families
      under 73 genera, and 45 new ethnomedicinal plant species are added. These 91
      locally used medicinal plants are found to treat 93 ailments. This study provides
      information on 45 plant species previously unknown for their medicinal uses in
      Manang. The indication for use, mode of preparation, dose and administration of
      medicine are described in detail for each species. CONCLUSION: This wealth of
      ethnobotanical knowledge persists, and is being transferred to the next
      generation in some areas in upper Manang, in a country where this is often not
      the case. The senior amchi of the area (Karma Sonam Lama), who has been
      practicing Tibetan medicine for three generations, feels that it is of utmost
      importance to conserve the traditional healing system and to pass his knowledge
      on to the local community about the importance of medicinal plants. He hopes that
      this will lead to the conservation and sustainable management of medicinal plants
      in the villages. Over the duration of this research, the prices of several rare
      medicinal plants of Manang increased dramatically, highlighting both the scarcity
      and the quick disappearance of the species. This is only one example of a
      worrying trend of over harvesting of medicinal plants, and highlights the need
      for conservation and management of medicinal plants of Manang district.

PMID- 17020611
TI  - Confirmation of emergence of mutations associated with atovaquone-proguanil
      resistance in unexposed Plasmodium falciparum isolates from Africa.
AB  - BACKGROUND: In vitro and in vivo resistance of Plasmodium falciparum to
      atovaquone or atovaquone-proguanil hydrochloride combination has been associated
      to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and
      Tyr268Asn). However, little is known about the prevalence of codon-268 mutations
      in natural populations of P. falciparum without previous exposure to the drug in
      Africa. METHODS: The prevalence of codon-268 mutations in the cytb gene of
      African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone
      proguanil has not been introduced for treatment of malaria was assessed.
      Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR
      restriction fragment length polymorphism and confirmed by sequencing. RESULTS:
      295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully
      analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268
      or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However,
      Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates
      from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an
      additional cytb mutation leading to a Pro266Thr substitution inside the
      ubiquinone reduction site. CONCLUSION: No Tyr268Ser mutation is found in cytb of
      P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for
      the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from
      Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn
      mutation is a matter of serious concern. Continuous monitoring of atovaquone
      proguanil resistant P. falciparum in Africa is warranted for the rational use of
      this new antimalarial drug, especially in non-immune travelers.

PMID- 17020613
TI  - Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an
      oncolytic adenovirus that targets colon cancer cells.
AB  - BACKGROUND: The Wnt signaling pathway is activated by mutations in the APC and
      beta-catenin genes in many types of human cancer. beta-catenin is stabilized by
      these mutations and activates transcription in part by acting as a bridge between
      Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously
      described oncolytic adenoviruses with binding sites for Tcf/LEF transcription
      factors inserted into the early viral promoters. These viruses replicate
      selectively in cells with activation of the Wnt pathway. To increase the activity
      of these viruses we have fused the viral transactivator E1A to the BCL9 HD2
      domain. METHODS: Luciferase assays, co-immunoprecipitation and Western blotting,
      immunofluorescent cell staining and cytopathic effect assays were used to
      characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of
      subcutaneous SW620 colon cancer xenografts were used to characterize the virus in
      vivo. RESULTS: The E1A-HD2 fusion protein binds to beta-catenin in vivo and
      activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells
      with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear
      import of beta-catenin, mediated by the strong nuclear localization signal in
      E1A. Tcf-regulated viruses expressing the fusion protein show increased
      expression of viral proteins and a five-fold increase in cytopathic effect (CPE)
      in colorectal cancer cell lines. There was no change in viral protein expression
      or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for
      cells with activation of the Wnt signaling pathway. Despite increasing the
      cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not
      increase the burst size of the virus in vitro or the anti-tumor effect of the
      virus in an SW620 xenograft model in vivo. CONCLUSION: Despite an increase in the
      nuclear pool of beta-catenin, the effects on viral activity in colon cancer cells
      were small, suggesting that factors acting downstream of beta-catenin are
      limiting for viral replication and toxicity in these cells. The approach of
      fusing E1A to a protein domain implicated in oncogenic signaling could be used to
      selectively increase the activity of oncolytic viruses targeting several other
      pathways defective in cancer.

PMID- 17020614
TI  - Psychometric evaluation and predictive validity of Ryff's psychological well
      being items in a UK birth cohort sample of women.
AB  - BACKGROUND: Investigations of the structure of psychological well-being items are
      useful for advancing knowledge of what dimensions define psychological well-being
      in practice. Ryff has proposed a multidimensional model of psychological well
      being and her questionnaire items are widely used but their latent structure and
      factorial validity remains contentious. METHODS: We applied latent variable
      models for factor analysis of ordinal/categorical data to a 42-item version of
      Ryff's psychological well-being scales administered to women aged 52 in a UK
      birth cohort study (n = 1,179). Construct (predictive) validity was examined
      against a measure of mental health recorded one year later. RESULTS: Inter-factor
      correlations among four of the first-order psychological well-being constructs
      were sufficiently high (> 0.80) to warrant a parsimonious representation as a
      second-order general well-being dimension. Method factors for questions
      reflecting positive and negative item content, orthogonal to the construct
      factors and assumed independent of each other, improved model fit by removing
      nuisance variance. Predictive validity correlations between psychological well
      being and a multidimensional measure of psychological distress were dominated by
      the contribution of environmental mastery, in keeping with earlier findings from
      cross-sectional studies that have correlated well-being and severity of
      depression. CONCLUSION: Our preferred model included a single second-order
      factor, loaded by four of the six first-order factors, two method factors, and
      two more distinct first-order factors. Psychological well-being is negatively
      associated with dimensions of mental health. Further investigation of precision
      of measurement across the health continuum is required.

PMID- 17020615
TI  - Androgen receptor expression in metastatic adenocarcinoma in females favors a
      breast primary.
AB  - BACKGROUND: The differential diagnosis of metastatic mammary adenocarcinoma and
      adenocarcinomas from other primary sites can be challenging, particularly in
      tumors that are poorly differentiated and negative for Estrogen/Progesterone
      receptors (ER/PR). With progression of disease, Androgen receptors (AR) are
      preserved with higher frequency than ER/PR in metastatic mammary carcinoma. This
      study was undertaken to evaluate the diagnostic significance of AR expression in
      adenocarcinoma of breast and other morphologically similar adenocarcinomas.
      DESIGN: Formalin-fixed paraffin-embedded tissue sections of 113 primary
      adenocarcinoma of various sites [breast (34, all females), lung (23, M- 6, F-17),
      colon (9, M-2, F-7), stomach (6, M-4, F-2), liver and bile duct (11, M-5, F-6),
      pancreas (7, M-2, F-5), ovary (10), endometrium (7), and cervix (6)] were
      immunostained with monoclonal antibody for AR. Except for well differentiated
      lobular carcinoma of breast (5) and bronchoalveolar carcinoma of lung (10),
      majority of the tumors were moderately to poorly differentiated. Tumors
      immunoreactive for > or = 10% of nuclei were considered AR positive. However, AR
      immunoreactivity in the cytoplasm only was also recorded. RESULTS: 56% (19/34)
      mammary carcinoma and 20% (2/10) adenocarcinoma of ovary were positive for AR.
      Remaining 69 adenocarcinomas did not show nuclear immunoreactivity for AR in > or
      = 10% nuclei; however, 52% (36/69) showed variable cytoplasmic immunoreactivity.
      CONCLUSION: Significant proportion of mammary carcinomas and some ovarian
      carcinomas express AR in the nuclei of more than 10% tumor cells. If metastatic
      tumor with unknown primary in a female is AR positive, breast and ovary are the
      most likely primary sites. Cytoplasmic immunoreactivity alone without nuclear
      immunoreactivity for AR was non-specific for this differential diagnosis.

PMID- 17020616
TI  - Biomarkers in chronic adult hydrocephalus.
AB  - Awareness of the importance of chronic adult hydrocephalus has been raised again
      with the recent emergence of epidemiological studies. It is estimated that
      between 5 and 10% of patients suffering from dementia might, in fact, have
      chronic hydrocephalus. Although, surgical diversion of the cerebrospinal fluid
      (CSF) represents the only known procedure able to treat the symptoms of this
      condition, the selection of surgical patients has always been problematic. In the
      last 40 years, we have become wiser in using appropriate diagnostic tests for the
      selection of these patients; however, the area of biological markers has so far
      been overlooked in this condition, in contrast to that for other
      neurodegenerative disorders and dementias. Biomarkers are biological substances
      that may be used to indicate either the onset or the presence, and the
      progression of a clinical condition, being closely linked to its pathophysiology.
      In such a setting they might assist in the more appropriate selection of patients
      for shunt surgery. In this article, we have reviewed research carried out in the
      last 25 years regarding the identification of serum and CSF biomarkers for
      chronic hydrocephalus, discussed the potential for each one, and finally
      discussed the limitations for use, as well as future directions and possibilities
      in this field. It is concluded that tumour-necrosis factor, tau protein, lactate,
      sulfatide and neurofilament triple protein are the most promising CSF markers for
      chronic hydrocephalus. At present however, none of these meet the criteria
      required to justify a change clinical practice. In the future, collaborative
      multi-centre projects will be needed to obtain more substantial data that
      overcome the problems that arise from small individual and uncoordinated studies.

PMID- 17020617
TI  - The crystal structure of superoxide dismutase from Plasmodium falciparum.
AB  - BACKGROUND: Superoxide dismutases (SODs) are important enzymes in defence against
      oxidative stress. In Plasmodium falciparum, they may be expected to have special
      significance since part of the parasite life cycle is spent in red blood cells
      where the formation of reactive oxygen species is likely to be promoted by the
      products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have
      potential as anti-malarial compounds. As a step towards their development we have
      determined the crystal structure of the parasite's cytosolic iron superoxide
      dismutase. RESULTS: The cytosolic iron superoxide dismutase from P. falciparum
      (PfFeSOD) has been overexpressed in E. coli in a catalytically active form. Its
      crystal structure has been solved by molecular replacement and refined against
      data extending to 2.5 A resolution. The structure reveals a two-domain
      organisation and an iron centre in which the metal is coordinated by three
      histidines, an aspartate and a solvent molecule. Consistent with
      ultracentrifugation analysis the enzyme is a dimer in which a hydrogen bonding
      lattice links the two active centres. CONCLUSION: The tertiary structure of
      PfFeSOD is very similar to those of a number of other iron-and manganese
      dependent superoxide dismutases, moreover the active site residues are conserved
      suggesting a common mechanism of action. Comparison of the dimer interfaces of
      PfFeSOD with the human manganese-dependent superoxide dismutase reveals a number
      of differences, which may underpin the design of parasite-selective superoxide
      dismutase inhibitors.

PMID- 17020618
TI  - Migrating leukocytes are the source of peroxiredoxin V during inflammation in the
      airways.
AB  - BACKGROUND: We characterized changes in expression of the antioxidant protein
      Peroxiredoxin V (PRXV) during airway inflammation. METHODS: Studies in
      anesthetized rats and mice; PRXV expression determined by Western blot analyses
      and immunohistochemistry; PRXV m-RNA expression determined by Taq-Man RT-PCR.
      RESULTS: Bacterial lung inflammation did not change expression of PRXV in murine
      epithelia but produced massive influx of leukocytes highly expressing PRXV.
      Endotoxin and f-MLP induced leukocyte migration in rat trachea but did not change
      mRNA levels and PRXV protein expression in tracheal epithelial cells. In primary
      airway cell culture (cow), alveolar epithelial cells A549, or co-culture of A549
      with murine macrophages RAW264.7, exposure to live bacteria increased expression
      of PRXV, which required serum. PRXV was secreted in vitro by epithelial and
      immune cells. CONCLUSION: Inflammation increased expression of PRXV in airways by
      at least 2 mechanisms: cell population shift by massive influx of leukocytes
      expressing PRXV, and moderate post-transcriptional up-regulation of PRXV in
      epithelial cells.

PMID- 17020619
TI  - Angiolymphoid hyperplasia with eosinophilia: efficacy of isotretinoin?
AB  - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign but
      potentially disfiguring vascular lesion. It is usually characterized by dermal
      and subcutaneous nodules, primarily in the head and neck region. Spontaneous
      regression is common, but persistent or recurrent lesions may require treatment.
      Several treatments have been reported but surgery is the most efficient one.
      METHODS AND RESULTS: We report a 32-year-old man presenting with multiple nodules
      on the cheeks, preauricular region and the scalp and who received treatment with
      isotretinoin (0.5 mg/kg/day) for 1 year with complete resolution of one of his
      scalp nodules. The rest of the lesions remained stable and were treated with
      surgical excision without recurrence. CONCLUSION: Isotretinoin may play a role in
      the treatment of ALHE due to its antiangiogenic properties via a reduction of
      vascular endothelial growth factor (VEGF) production by keratinocytes.

PMID- 17020620
TI  - Randomized trial of exercise in sedentary middle aged women: effects on quality
      of life.
AB  - Increasing physical activity is currently considered to be a possible prevention
      strategy for cancer, obesity, and cardiovascular disease, either alone or in
      combination with dietary changes. This paper presents results of a randomized
      trial of moderate-to-vigorous intensity exercise in middle aged, sedentary women;
      specifically, we report changes in and correlates of quality of life and
      functional status of this exercise intervention program for both the short (three
      months) and longer term (12 months). The intervention group showed a significant
      increase in Mental Health score from baseline to 3 months (p < .01),
      significantly greater than the change in the control group at 3 months (p < .01).
      A similar trend among exercisers was observed for the General Health score (p <
      .01), and this finding was significantly greater than the change in control group
      at 3 months (p = .01). Change in Social Support - Affection were predictors of
      the changes in quality of life variables. This study documented improvements in
      quality of life and general functioning that occurred as a result of
      participating in an exercise intervention in sedentary middle-aged women.

PMID- 17020621
TI  - Comparison of proteomic profiles of serum, plasma, and modified media supplements
      used for cell culture and expansion.
AB  - BACKGROUND: The culture and expansion of human cells for clinical use requires
      the presence of human serum or plasma in culture media. Although these
      supplements have been extensively characterized in their chemical composition,
      only recently it has been possible to provide by high throughput protein
      analysis, a comprehensive profile of the soluble factors contributing to cell
      survival. This study analyzed and compared the presence of 100 proteins including
      chemokines, cytokines and soluble factors in six different types of media
      supplements: serum, plasma, recalcified plasma, heat inactivated serum, heat
      inactivated plasma and heat inactivated recalcified plasma. METHODS: Serum,
      plasma, recalcified plasma, and heat inactivated supplements were prepared from
      ten healthy subjects. The levels of 100 soluble factors were measured in each
      sample using a multiplexed ELISA assay and compared by Eisen hierarchical
      clustering analysis. RESULTS: A comparison of serum and plasma levels of soluble
      factors found that 2 were greater in plasma but 18 factors were greater in serum
      including 11 chemokines. The levels of only four factors differed between
      recalcified plasma and plasma. Heat inactivation had the greatest effect on
      soluble factors. Supervised Eisen hierarchical clustering indicated that the
      differences between heat inactivated supplements and those that were not were
      greater than the differences within these two groups. The levels of 36 factors
      differed between heat inactivated plasma and plasma. Thirty one of these factors
      had a lower concentration in heat inactivated plasma including 12 chemokines, 4
      growth factors, 4 matrix metalloproteases, and 3 adhesion molecules. Heat
      inactivated decalcified plasma is often used in place of heat inactivated serum
      and the levels of 19 soluble factors differed between these two supplements.
      CONCLUSION: Our report provides a comprehensive protein profile of serum, plasma
      recalcified plasma, and heat inactivated supplements. This profile represents a
      qualitative and quantitative database that can aid in the selection of the
      appropriate blood derived supplement for human cell cultures with special
      requirements.

PMID- 17020622
TI  - Depression in mothers of children with thalassemia or blood malignancies: a study
      from Iran.
AB  - BACKGROUND: Several studies have found that parents of children with chronic
      diseases or disabilities have higher depression scores than control parents.
      Mothers usually take on the considerable part of the extra care and support that
      these children need and thus are at markedly increased risks of suffering from
      psychological distress and depression. The main aim of the present study was to
      investigate if mothers of children with thalassemia or blood malignancies have
      higher scores of depression compared with a group of control mothers. METHODS AND
      MATERIALS: In this cross - sectional study, 294 mothers were recruited in three
      groups and assessed using the Beck Depression Inventory (BDI): mothers of
      children with thalassemia, mothers of children with blood malignancies and a
      control group. SPSS version 11.5 with chi square, ANOVA, linear and logistic
      regression were used for statistical analysis. RESULTS: The only variable bearing
      a statistically significant relationship with the depression score of mothers was
      the child's disease: for thalassemia with OR of 2.17 (95% CI = 1.16-4.0, P =
      0.015), for blood malignancies with OR of 2.71 (95% CI = 1.48-4.99, P = 0.001).
      DISCUSSION AND CONCLUSION: The results of this study can contribute to the
      development of a screening program for decreasing depression burden and promoting
      quality of life for mothers of children with thalassemia or blood malignancies.

PMID- 17020623
TI  - Smoking in film in New Zealand: measuring risk exposure.
AB  - BACKGROUND: Smoking in film is a risk factor for smoking uptake in adolescence.
      This study aimed to quantify exposure to smoking in film received by New Zealand
      audiences, and evaluate potential interventions to reduce the quantity and impact
      of this exposure. METHODS: The ten highest-grossing films in New Zealand for 2003
      were each analysed independently by two viewers for smoking, smoking references
      and related imagery. Potential interventions were explored by reviewing relevant
      New Zealand legislation, and scientific literature. RESULTS: Seven of the ten
      films contained at least one tobacco reference, similar to larger film samples.
      The majority of the 38 tobacco references involved characters smoking, most of
      whom were male. Smoking was associated with positive character traits, notably
      rebellion (which may appeal to adolescents). There appeared to be a low threshold
      for including smoking in film. Legislative or censorship approaches to smoking in
      film are currently unlikely to succeed. Anti-smoking advertising before films has
      promise, but experimental research is required to demonstrate cost effectiveness.
      CONCLUSION: Smoking in film warrants concern from public health advocates. In New
      Zealand, pre-film anti-smoking advertising appears to be the most promising
      immediate policy response.

PMID- 17020624
TI  - High fidelity medical simulation in the difficult environment of a helicopter:
      feasibility, self-efficacy and cost.
AB  - BACKGROUND: This study assessed the feasibility, self-efficacy and cost of
      providing a high fidelity medical simulation experience in the difficult
      environment of an air ambulance helicopter. METHODS: Seven of 12 EM residents in
      their first postgraduate year participated in an EMS flight simulation as the
      flight physician. The simulation used the Laerdal SimMantrade mark to present a
      cardiac and a trauma case in an EMS helicopter while running at flight idle.
      Before and after the simulation, subjects completed visual analog scales and a
      semi-structured interview to measure their self-efficacy, i.e. comfort with their
      ability to treat patients in the helicopter, and recognition of obstacles to care
      in the helicopter environment. After all 12 residents had completed their first
      non-simulated flight as the flight physician; they were surveyed about self
      assessed comfort and perceived value of the simulation. Continuous data were
      compared between pre- and post-simulation using a paired samples t-test, and
      between residents participating in the simulation and those who did not using an
      independent samples t-test. Categorical data were compared using Fisher's exact
      test. Cost data for the simulation experience were estimated by the
      investigators. RESULTS: The simulations functioned correctly 5 out of 7 times;
      suggesting some refinement is necessary. Cost data indicated a monetary cost of
      440 dollars and a time cost of 22 hours of skilled instructor time. The
      simulation and non-simulation groups were similar in their demographics and pre
      hospital experiences. The simulation did not improve residents' self-assessed
      comfort prior to their first flight (p > 0.234), but did improve understanding of
      the obstacles to patient care in the helicopter (p = 0.029). Every resident
      undertaking the simulation agreed it was educational and it should be included in
      their training. Qualitative data suggested residents would benefit from high
      fidelity simulation in other environments, including ground transport and for
      running codes in hospital. CONCLUSION: It is feasible to provide a high fidelity
      medical simulation experience in the difficult environment of the air ambulance
      helicopter, although further experience is necessary to eliminate practical
      problems. Simulation improves recognition of the challenges present and provides
      an important opportunity for training in challenging environments. However, use
      of simulation technology is expensive both in terms of monetary outlay and of
      personnel involvement. The benefits of this technology must be weighed against
      the cost for each institution.

PMID- 17020625
TI  - Unusual positron emission tomography findings in pulmonary amyloidosis: a case
      report.
AB  - Positron emission tomography (PET) has come to play an increasingly important
      role in the evaluation of pulmonary lesions, which are suspicious of malignancy.
      As is true for other techniques, PET gives false positive and negative results.
      We report a case of pulmonary amyloidosis with multiple pulmonary nodules showing
      different uptake of 18 F-fluorodeoxyglucose (FDG) on PET. There are limitations
      of specificity of FDG-PET in characterising pulmonary nodules and it is important
      to confirm a suspected malignancy with histology before potentially curative
      treatment is undertaken.

PMID- 17020626
TI  - Hierarchical decomposition of dichoptic multifocal visual evoked potentials.
AB  - Visual evoked responses to dichoptically presented multifocal stimuli were
      recorded for 92 eyes. Two stimulus variants were explored: temporally sparse and
      rapidly contrast reversing. We used hierarchical decomposition (HD) to represent
      the multifocal responses in terms of a small number of potentially unique
      component waveforms that are interrelated in a multivariate linear autoregressive
      (MLAR) relationship. The HD method exploits temporal correlations over a range of
      delays in the responses to estimate parallel, feedforward and feedback
      relationships between the HD components. Three HD components having temporal
      interrelationships constrained (at P < 0.05) to a moving approximately 20 ms
      window could describe the multifocal responses well (median r2-values up to 90%).
      HD components were similar for both stimulus types and the component waveforms
      were temporally correlated, especially the first and third components. The data
      set was large enough to estimate separate HD components for each multifocal
      stimulus region. The component waveforms differed somewhat by region but the MLAR
      relationships were similar. At short delays parallel processing dominated. At
      longer delays the proportion of response drives that were attributed to feedback
      and feedforward relationships grew. Overall HD analysis seems to provide an
      informed summary of multifocal responses and insights into their sources.

PMID- 17020627
TI  - Current source density analysis of contra- and ipsilateral isthmotectal
      connections of the frog.
AB  - The nucleus isthmi (NI) of the frog receives input from the ipsilateral optic
      tectum and projects back to both optic tecta. After ablation of NI, frogs display
      no visually elicited prey-catching or threat avoidance behavior. Neural
      mechanisms that underlie the loss of such important behavior have not been
      solved. Electrophysiological examination of the contralateral isthmotectal
      projection has proved that it contributes to binocular vision. On the other hand,
      there are very few physiological investigations of the ipsilateral isthmotectal
      projection. In this study, current source density (CSD) analysis was applied to
      contra- and ipsilateral isthmotectal projections. The contralateral projection
      produced monosynaptic sinks in superficial layers and in layer 8. The results
      confirmed former findings obtained by single unit recordings. The ipsilateral
      projection elicited a prominent monosynaptic sink in layer 8. Recipient neurons
      were located in layers 6-7. These results, combined with those from the former
      intracellular study, led to the following neuronal circuit. Afferents from the
      ipsilateral NI inhibit non-efferent pear shaped neurons in the superficial
      layers, and strongly excite large ganglionic neurons projecting to the descending
      motor regions. Thus feedback to the output neurons strengthens the visually
      elicited responses.

PMID- 17020628
TI  - The maximum range and timing of excitatory contextual modulation in monkey
      primary visual cortex.
AB  - Contextual modulations of receptive field properties by distal stimulus
      configurations have been shown for a variety of stimulus paradigms. A survey of
      excitatory contextual modulation data for V1 shows the maximum scale of
      interactions, measured in terms of distance in V1, to be between 10 mm and 30 mm.
      Different types of excitatory contextual modulation in V1 occur throughout the
      interval of 40-250 ms after stimulus delivery. This window provides opportunity
      for global propagation of visual contextual information to a subset of V1
      neurons, via several routes within the visual system. We propose a number of
      experiments and analyses to confirm the results from this empirical survey.

PMID- 17020629
TI  - Directional shifts in the barber pole illusion: effects of spatial frequency,
      spatial adaptation, and lateral masking.
AB  - We report the results of psychophysical experiments with the so-called barber
      pole stimulus providing new insights on the neuronal processes underlying the
      analysis of moving features such as terminators or line-endings. In experiment 1,
      we show that the perceived direction of a barber pole stimulus, induced by line
      ending motion, is highly dependent on the spatial frequency and contrast of the
      grating stimulus: perceived direction is shifted away from the barber pole
      illusion at high spatial frequency in a contrast dependent way, suggesting that
      line-ends are not processed at high spatial scales. In subsequent experiments, we
      use a contrast adaptation paradigm and a masking paradigm in an attempt to assess
      the spatial structure and location of the receptive fields that process line
      endings. We show that the adapting stimulus that weakens most the barber pole
      illusion is localized within the barber pole stimulus and not at line-endings'
      locations. Current models of line-endings' motion processing are discussed in the
      light of these psychophysical results.

PMID- 17020630
TI  - Dark rearing reveals the mechanism underlying stimulus size tuning of superior
      colliculus neurons.
AB  - Neurons in the superficial layers of the midbrain superior colliculus (SC)
      exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the
      geniculocortical visual pathway, most respond best to visual stimuli that are
      smaller than the classical receptive field (RF). The mechanism underlying this
      size selectivity may depend on the number and pattern of feedforward retinal
      inputs and/or the balance between inhibition and excitation within the RF. We
      have previously shown that chronic blockade of NMDA receptors (NMDA-R), which
      increases the convergence of retinal afferents onto SC neurons, does not alter
      size selectivity in the SC. This suggests that the number of retinal inputs does
      not determine size selectivity. Here we show, using single unit extracellular
      recordings from the SC of normal hamsters, that size selectivity in neurons
      selective for small stimulus size is correlated with the strength of inhibition
      within the RF. We also show that dark rearing causes concomitant reductions in
      both inhibition and size selectivity. In addition, dark rearing increases the
      percentage of neurons non-selective for stimulus size. Finally, we show that
      chronic blockade of NMDA-R, a procedure that does not alter size tuning, also
      does not change the strength of inhibition within the RF. Taken together, these
      results argue that inhibition within the RF underlies selectivity for small
      stimulus size and that inhibition must be intact for size tuning to be preserved
      after developmental manipulations of activity. In addition, these results suggest
      that regulation of the balance between excitation and inhibition within the RF
      does not require NMDA-R activity but does depend on visual experience. These
      results suggest that developmental experience influences neural response
      properties through an alteration of inhibitory circuitry.

PMID- 17020631
TI  - Temporal dynamics of 2D and 3D shape representation in macaque visual area V4.
AB  - We studied the temporal dynamics of shape representation in area V4 of the alert
      macaque monkey. Analyses were based on two large stimulus sets, one equivalent to
      the 2D shape stimuli used in a previous study of V2, and the other a set of
      stereoscopic 3D shape stimuli. As in V2, we found that information conveyed by
      individual V4 neurons about the stimuli tended to be maximal during the initial
      transient response and generally lower, albeit statistically significant,
      afterwards. The population response was substantially correlated from one
      stimulus to the next during the transients, and decorrelated as responses
      decayed. V4 responses showed significantly longer latencies than in V2,
      especially for the 3D stimulus set. Recordings from area V1 in a single animal
      revealed temporal dynamic patterns in response to the 2D shape stimuli that were
      largely similar to those in V2 and V4. Together with earlier results, these
      findings provide evidence for a distributed process of coarse-to-fine
      representation of shape stimuli in the visual cortex.

PMID- 17020632
TI  - The squirrel as a rodent model of the human visual system.
AB  - Over the last 50 years, studies of receptive fields in the early mammalian visual
      system have identified many classes of response properties in brain areas such as
      retina, lateral geniculate nucleus (LGN), and primary visual cortex (V1).
      Recently, there has been significant interest in understanding the cellular and
      network mechanisms that underlie these visual responses and their functional
      architecture. Small mammals like rodents offer many advantages for such studies,
      because they are appropriate for a wide variety of experimental techniques.
      However, the traditional rodent models, mice and rats, do not rely heavily on
      vision and have small visual brain areas. Squirrels are highly visual rodents
      that may be excellent model preparations for understanding mechanisms of function
      and disease in the human visual system. They use vision for navigating in their
      environment, predator avoidance, and foraging for food. Visual brain areas such
      as LGN, V1, superior colliculus, and pulvinar are particularly large and well
      elaborated in the squirrel, and the squirrel has several extrastriate cortical
      areas lateral to V1. Unlike many mammals, most squirrel species are diurnal with
      cone-dominated retinas, similar to the primate fovea, and have excellent
      dichromatic color vision that is mediated by green and blue cones. Owing to their
      larger size, squirrels are physiologically more robust than mice and rats under
      anesthesia, and some hibernating species are particularly tolerant of hypoxia
      that occurs during procedures such as brain slicing. Finally, many basic
      anatomical and physiological properties in the early visual system of squirrel
      have now been described, permitting investigations of cellular mechanisms. In
      this article, we review four decades of anatomical, behavioral, and physiological
      studies in squirrel and make comparisons with other species.

PMID- 17020634
TI  - Ocular dominance columns in strabismus.
AB  - During development, the projection from the lateral geniculate nucleus to striate
      cortex becomes segregated into monocular regions called ocular dominance columns.
      Prior studies in cats have suggested that experimental strabismus or alternating
      monocular occlusion increases the width and segregation of columns. In the
      squirrel monkey, strabismus has been reported to induce the formation of ocular
      dominance columns. However, these studies are difficult to interpret because no
      animal can serve as its own control and the degree of inter-individual
      variability among normal subjects is considerable. We have re-examined the effect
      of strabismus on ocular dominance columns in a large group of strabismic and
      normal squirrel monkeys. Five animals rendered strabismic at age one week had
      well-developed, widely spaced columns. Among 16 control animals, a wide spectrum
      of column morphology was encountered. Some control animals lacked ocular
      dominance columns, whereas others had columns similar to those observed in
      strabismic animals. Natural variation in column expression in normal squirrel
      monkeys, and potential uncontrolled genetic influences, made it impossible to
      determine if strabismus affects ocular dominance columns. It was evident however,
      that strabismus does not affect the binocular projection from the lateral
      geniculate nucleus to each CO patch in the upper layers. In strabismic monkeys,
      just as in normal animals, each patch received input from geniculate afferents
      serving both the left eye and the right eye. In addition, in strabismic monkeys,
      as in normal animals, patches were not aligned with ocular dominance columns.

PMID- 17020633
TI  - A high frequency resonance in the responses of retinal ganglion cells to rapidly
      modulated stimuli: a computer model.
AB  - Brisk Y-type ganglion cells in the cat retina exhibit a high frequency resonance
      (HFR) in their responses to large, rapidly modulated stimuli. We used a computer
      model to test whether negative feedback mediated by axon-bearing amacrine cells
      onto ganglion cells could account for the experimentally observed properties of
      HFRs. Temporal modulation transfer functions (tMTFs) recorded from model ganglion
      cells exhibited HFR peaks whose amplitude, width, and locations were
      qualitatively consistent with experimental data. Moreover, the wide spatial
      distribution of axon-mediated feedback accounted for the observed increase in HFR
      amplitude with stimulus size. Model phase plots were qualitatively similar to
      those recorded from Y ganglion cells, including an anomalous phase advance that
      in our model coincided with the amplification of low-order harmonics that
      overlapped the HFR peak. When axon-mediated feedback in the model was directed
      primarily to bipolar cells, whose synaptic output was graded, or else when the
      model was replaced with a simple cascade of linear filters, it was possible to
      produce large HFR peaks but the region of anomalous phase advance was always
      eliminated, suggesting the critical involvement of strongly non-linear feedback
      loops. To investigate whether HFRs might contribute to visual processing, we
      simulated high frequency ocular tremor by rapidly modulating a naturalistic
      image. Visual signals riding on top of the imposed jitter conveyed an enhanced
      representation of large objects. We conclude that by amplifying responses to
      ocular tremor, HFRs may selectively enhance the processing of large image
      features.

PMID- 17020635
TI  - Dissociated GABAergic retinal interneurons exhibit spontaneous increases in
      intracellular calcium.
AB  - Early in development, before the retina is responsive to light, neurons exhibit
      spontaneous activity. Recently it was demonstrated that starburst amacrine cells,
      a unique class of neurons that secretes both GABA and acetylcholine,
      spontaneously depolarize. Networks comprised of spontaneously active starburst
      cells initiate correlated bursts of action potentials that propagate across the
      developing retina with a periodicity on the order minutes. To determine whether
      other retinal interneurons have similar "pacemaking" properties, we have utilized
      cultures of dissociated neurons from the rat retina. In the presence of
      antagonists for fast neurotransmitter receptors, distinct populations of neurons
      exhibited spontaneous, uncorrelated increases in intracellular calcium
      concentration. These increases in intracellular calcium concentration were
      sensitive to tetrodotoxin, indicating they are mediated by spontaneous membrane
      depolarizations. By combining immunofluorescence and calcium imaging, we found
      that 44% of spontaneously active neurons were GABAergic and included starburst
      amacrine cells. Whole cell voltage clamp recordings in the absence of antagonists
      for fast neurotransmitters revealed that after 7 days in culture, individual
      retinal neurons receive bursts of GABA-A receptor mediated synaptic input with a
      periodicity similar to that measured in spontaneously active GABAergic neurons.
      Low concentrations of GABA-A receptor antagonists did not alter the inter-burst
      interval despite significant reduction of post-synaptic current amplitude,
      indicating that pacemaker activity of GABAergic neurons was not influenced by
      network interactions. Together, these findings indicate that spiking GABAergic
      interneurons can function as pacemakers in the developing retina.

PMID- 17020636
TI  - Processing of first-order motion in marmoset visual cortex is influenced by
      second-order motion.
AB  - We measured the responses of single neurons in marmoset visual cortex (V1, V2,
      and the third visual complex) to moving first-order stimuli and to combined first
      and second-order stimuli in order to determine whether first-order motion
      processing was influenced by second-order motion. Beat stimuli were made by
      summing two gratings of similar spatial frequency, one of which was static and
      the other was moving. The beat is the product of a moving sinusoidal carrier
      (first-order motion) and a moving low-frequency contrast envelope (second-order
      motion). We compared responses to moving first-order gratings alone with
      responses to beat patterns with first-order and second-order motion in the same
      direction as each other, or in opposite directions to each other in order to
      distinguish first-order and second-order direction-selective responses. In the
      majority (72%, 67/93) of cells (V1 73%, 45/62; V2 70%, 16/23; third visual
      complex 75%, 6/8), responses to first-order motion were significantly influenced
      by the addition of a second-order signal. The second-order envelope was more
      influential when moving in the opposite direction to the first-order stimulus,
      reducing first-order direction sensitivity in V1, V2, and the third visual
      complex. We interpret these results as showing that first-order motion processing
      through early visual cortex is not separate from second-order motion processing;
      suggesting that both motion signals are processed by the same system.

PMID- 17020637
TI  - Modulation of A-type potassium currents in retinal horizontal cells by
      extracellular calcium and zinc.
AB  - Extracellular Ca2+ and Zn2+ influence many aspects of retinal function. Here, we
      examined the effect of external Ca2+ and Zn2+ on potassium channels of retinal
      horizontal cells. When extracellular Ca2+ was lowered from 3 mM to 0.3 mM,
      horizontal cell transient outward currents elicited by voltage steps from resting
      membrane potential (-70 mV) were decreased by approximately 50%, whereas the
      sustained currents remained unchanged. This effect was due to a hyperpolarizing
      shift in the steady-state inactivation curve of A-type K+ currents when
      extracellular Ca2+ concentration was lowered. The mean half inactivation
      potential of the steady-state inactivation curves was hyperpolarized from -56.3
      +/- 4.7 mV in 3 mM Ca2+ to -76.4 +/- 3.9 mV in 0.3 mM Ca2+. Neither the state
      steady activation curve nor the kinetics of inactivation was significantly
      changed in low extracellular Ca2+. The addition of 30 microM Zn2+ restored peak
      outward currents in 0.3 mM Ca2+. The half inactivation voltages were depolarized
      from -70 +/- 2.8 mV in 0.3 mM Ca2+ to -56 +/- 2.6 mV in 0.3 mM Ca2+ plus 30
      microM Zn2+. Taken together, the results indicate that external Ca2+ and Zn2+
      maintain the activity of A-type potassium channels in retinal horizontal cells by
      influencing the voltage dependence of steady-state inactivation.

PMID- 17020638
TI  - In vivo development of retinal ON-bipolar cell axonal terminals visualized in
      nyx::MYFP transgenic zebrafish.
AB  - Axonal differentiation of retinal bipolar cells has largely been studied by
      comparing the morphology of these interneurons in fixed tissue at different ages.
      To better understand how bipolar axonal terminals develop in vivo, we imaged
      fluorescently labeled cells in the zebrafish retina using time-lapse confocal and
      two photon microscopy. Using the upstream regulatory sequences from the nyx gene
      that encodes nyctalopin, we constructed a transgenic fish in which a subset of
      retinal bipolar cells express membrane targeted yellow fluorescent protein
      (MYFP). Axonal terminals of these YFP-labeled bipolar cells laminated primarily
      in the inner half of the inner plexiform layer, suggesting that they are likely
      to be ON-bipolar cells. Transient expression of MYFP in isolated bipolar cells
      indicates that two or more subsets of bipolar cells, with one or two terminal
      boutons, are labeled. Live imaging of YFP-expressing bipolar cells in the
      nyx::MYFP transgenic fish at different ages showed that initially, filopodial
      like structures extend and retract from their primary axonal process throughout
      the inner plexiform layer (IPL). Over time, filopodial exploration becomes
      concentrated at discrete foci prior to the establishment of large terminal
      boutons, characteristic of the mature form. This sequence of axonal
      differentiation suggests that synaptic targeting by bipolar cell axons may
      involve an early process of trial and error, rather than a process of directed
      outgrowth and contact. Our observations represent the first in vivo visualization
      of axonal development of bipolar cells in a vertebrate retina.

PMID- 17020639
TI  - Nutrition in primary health care: using a Delphi process to design new
      interdisciplinary services.
AB  - PURPOSE: A modified Delphi process was used to identify key features of
      interdisciplinary nutrition services, including provider roles and
      responsibilities for Ontario Family Health Networks (FHNs), a family physician
      based type of primary care. METHODS: Twenty-three representatives from interested
      professional organizations, including three FHN demonstration sites, completed a
      modified Delphi process. Participants reviewed evidence from a systematic
      literature review, a patient survey, a costing analysis, and key informant
      interview results before undertaking the Delphi process. Statements describing
      various options for services were developed at an in-person meeting, which was
      followed by two rounds of e-mail questionnaires. Teleconference discussions were
      held between rounds. RESULTS: An interdisciplinary model with differing and
      complementary roles for health care providers emerged from the process.
      Additional key features addressing screening for nutrition problems, health
      promotion and disease prevention, team collaboration, planning and evaluation,
      administrative support, access to care, and medical directives/delegated acts
      were identified. Under the proposed model, the registered dietitian is the team
      member responsible for managing all aspects of nutrition services, from needs
      assessment to program delivery, as well as for supporting all providers'
      nutrition services. CONCLUSIONS: The proposed interdisciplinary nutrition
      services model merits evaluation of cost, effectiveness, applicability, and
      sustainability in team-based primary care service settings.

PMID- 17020640
TI  - Guest editorial dietitians in the right place at the right time for primary
      health care.

PMID- 17020641
TI  - Estimation of human resource needs and cost of adding registered dietitians to
      primary care networks.
AB  - PURPOSE: Information on human resources and costs is needed to plan for the
      addition of registered dietitian (RD) services to new models of primary health
      care (PHC). Estimates were developed, based on an analysis of an enhanced RD
      model of counselling and health promotion services in three Ontario Family Health
      Networks (FHNs). METHODS: Both direct and indirect costs were averaged over the
      three FHNs. Costs and RD activities were tracked throughout 2005. The FHN staff
      completed two questionnaires addressing communication, case management, and
      satisfaction with RD services. RESULTS: Actual and reported case management
      indicated that an estimated 1.3% to 2.4% of the 60,000 enrolled patients may
      require individual nutrition counselling in a year. If one full-time equivalent
      (FTE) RD can manage 380 new referrals, then one FTE RD is needed per 15,800 to
      29,000 patients. The estimated direct costs of adding one FTE RD (including
      expenses and fixed costs) is US dollars 78,169 to US dollars 80,169, when the RD
      is an independent contractor. CONCLUSIONS: Additional studies are needed to
      develop better estimates of human resource needs and costs of interdisciplinary
      nutrition services in all PHC settings. These estimates should be based on
      population characteristics and direct and indirect costs for all models of
      nutrition services in PHC settings.

PMID- 17020642
TI  - Promoting healthy lifestyles in Ontario Family Health Networks.
AB  - PURPOSE: Primary health care reform presents new opportunities for registered
      dietitians (RDs) to contribute to health promotion and disease prevention in
      family practices. Since this is an emerging area of RD practice, a health
      promotion specialist was contracted to conduct a needs assessment and develop a
      plan for implementing nutrition-focused healthy lifestyle activities. METHODS:
      The needs assessment was conducted as part of an Ontario-based demonstration
      project in three Family Health Networks (FHNs). RESULTS: The needs assessment
      revealed a lack of agreement about what types of activities should be undertaken,
      a lack of information on the population's needs, a lack of coordination with
      other agencies in the community, and barriers of time and resources. The health
      promotion specialist recommended that health care team members in each FHN
      develop a shared understanding of their goals, and undertake the entire planning
      and evaluation cycle. Specific strategies were suggested to increase awareness,
      to provide health education, and to improve environmental support. CONCLUSIONS: A
      significant need exists for conceptual development, planning, testing, and
      evaluation of disease prevention and health promotion in family physician-based
      primary health care organizations. The findings may be useful to others
      interested in increasing the focus on health promotion and disease prevention in
      such practices.

PMID- 17020643
TI  - Enhancing interdisciplinary collaboration in primary health care.
AB  - BACKGROUND: Dietitians of Canada has endorsed the Principles and Framework for
      Enhancing Interdisciplinary Collaboration in Primary Health Care (EICP) created
      by the EICP Initiative. The Initiative focused on the conditions required for
      health professionals to work together in the most effective and efficient way, so
      that they can produce the best health outcomes for individuals and their families
      -the patients, clients, and consumers of our national health system. The
      Initiative was spearheaded by a Steering Committee of 11 national health
      professional organizations, and brought together leaders, health professionals,
      and key stakeholders in Canada's primary health care system in a change process
      designed to facilitate more interdisciplinary collaboration. PRINCIPLES AND
      FRAMEWORK: In the context of the EICP Initiative, the Principles are values
      shared by stakeholders. They are critical to the establishment of collaboration
      and teamwork to achieve the best health outcomes. The elements of the Principles
      are patient/client engagement, a population health approach, the best possible
      care and services, access, trust and respect, and effective communication. The
      Framework builds upon these Principles and is composed of the structural and
      process elements required to support collaborative primary health care. The
      elements of the Framework are health human resources, funding, liability,
      regulation, information and communications technology, management and leadership,
      and planning and evaluation. CONCLUSIONS: The Boards of Directors of the ten
      health professions leading the EICP Initiative agreed upon the values and key
      structural and process elements that need to be put in place to enhance
      interdisciplinary collaboration in Primary Health Care in Canada. Dietitians of
      Canada will continue to seek opportunities to further the change process started
      by EICP. Approximately 40 research papers and a toolkit to help primary heath
      care providers work together have been produced.

PMID- 17020644
TI  - Primary health care, mental health, and the dietitian's role.
AB  - PURPOSE: Individuals with mental illness are at nutritional risk because of
      health, social, and economic factors. To address this problem, the Canadian
      Collaborative Mental Health Initiative (CCMHI) and Dietitians of Canada (DC)
      commissioned the development of a toolkit that outlines the role of the
      registered dietitian (RD) and advocates for RDs in primary health care (PHC)
      mental health programs. METHODS: The development of the toolkit followed a four
      stage process: a comprehensive literature review, a focus group discussion with a
      national working group, interviews with consumers about RD services, and
      evaluation of the toolkit. RESULTS: The costs of mental illness in Canada are at
      least US dollars 6.85 billion per year. Currently, little evidence exists on how
      RD services can reduce these expenses. The focus group identified accessibility
      as the predominant issue facing individuals with mental illness. To explain
      consumer experiences with RD services, a three-tier theory based on in-depth
      interviews was developed. Consumer experiences with RDs occur in five categories:
      financial concerns, perception of service, status of mental illness, engagement,
      and self-esteem (tier 1). These are further influenced by five individual and
      contextual factors, e.g., social environment, the mental illness (tier 2), which
      are weighed as benefits and barriers instrumental in determining actions (tier
      3). CONCLUSIONS: The evaluation of the final draft of the RD toolkit confirmed
      that it reflected the visions of PHC. The toolkit is intended to act as a
      blueprint for action. Dietitians are encouraged to use its contents to advocate
      for positions in mental health PHC settings.

PMID- 17020645
TI  - Building a vision of dietitian services in primary health care.
AB  - PURPOSE: Primary health care (PHC) reform, especially efforts to implement
      interdisciplinary teams, has implications for dietetic practice. A consistent,
      clear vision of the registered dietitian's (RD's) role in PHC is needed to
      develop a successful advocacy agenda. METHODS: The Dietitians of Canada (DC)
      Central and Southern Ontario Primary Health Care Action Group organized a four
      step process to engage dietitians in developing an advocacy agenda for RD PHC
      services in Ontario. Two facilitated workshops brought together dietitian opinion
      leaders to enhance the understanding of current roles, find common ground, and
      develop a shared vision. All DC members were invited to review the draft vision,
      and feedback was integrated into a revised vision. RESULTS: Registered dietitians
      saw PHC reform through many lenses, and were uncertain about how reforms would
      affect their practices. In a national review, the majority of reviewers
      (approximately 85% of 270) supported the draft vision; additional clarity was
      needed on resources and the breadth of services that RDs would provide.
      CONCLUSION: Development of a PHC vision for RDs should be helpful in advocating
      for dietitian services in PHC.

PMID- 17020646
TI  - Common ground: the canadian collaborative mental health initiative.
AB  - BACKGROUND: As one of 12 participating national health associations, Dietitians
      of Canada (DC) endorsed the Charter Principles and Commitments created by the
      Canadian Collaborative Mental Health Initiative (CCMHI). The Chair of the DC
      Board of Directors signed the Charter, committing DC to work collaboratively to
      uphold the Principles and actively endorse the Commitments. ACHIEVEMENTS: The
      Initiative's vision, making mental health care work--new places, new partners,
      new hope, provided the Steering Committee with a clear direction. The CCMHI
      Charter Principles cover promotion and prevention, a holistic approach,
      collaboration, partnership, respect, information exchange, and resources. In
      addition to the Charter, the CCMHI has produced a series of 12 toolkits and
      research papers. The toolkits are practical pieces that also contain ideas and
      other information. Dietitians of Canada has developed a toolkit that examines the
      dietitian's role in primary health care mental health programs. A set of reviews
      of the practice of collaborative mental health care in Canada covers a wide range
      of issues, from the attributes of effective collaborative care to a discussion of
      the barriers to collaboration. CONCLUSION: Communications between the 12 member
      organizations are ongoing, and the organizations await the establishment of the
      Canadian Mental Health Commission, which is expected to be up and running in fall
      2006.

PMID- 17020647
TI  - [Influence of different parameters on final height of boys with constitutional
      delay of growth and puberty].
AB  - BACKGROUND: Constitutional delay of growth and puberty (CDGP) is a variant of
      normal pattern of growth and development with strong familial impact. THE AIM of
      the study was to assess the influence of birth weight and length, parents'
      height, boys height and bone age at the age of 14-16 years and mutation age on
      their final height. MATERIAL AND METHODS: In 69 boys in the mean age of 14.9+/
      1.2 years, whose height fell below the 3rd percentile, CDGP was diagnosed. After
      completion of growth (at the age of 22.6+/-3.5 years) correlations of different
      parameters with final height were estimated. RESULTS: Statistically significant
      correlation between birth weight, parents' height, mutation age and final height
      was observed, but no association between birth length, height and bone age in the
      age group of 14-16 years and the final height was found. CONCLUSIONS: Adult
      height of boys with CDGP is directly proportional to birth weight, mutation age
      and parents' height.

PMID- 17020648
TI  - [The frequency of CTLA-4 gene polymorphism at position 49 exon 1 in children with
      Hashimoto's thyroiditis].
AB  - INTRODUCTION: The cytotoxic T lymphocyte antigen-4 (CTLA-4) is a molecule present
      on T cells that plays a critical role in the down regulation of antigen-activated
      immune responses. Its gene polymorphism is a strong candidate gene for conferring
      susceptibility to thyroid autoimmunity. THE AIM of the study was to analyse the
      frequency of CTLA-4 exon 1 polymorphism (A49G) in children with Hashimoto's
      thyroiditis. MATERIAL AND METHODS: Blood samples from 68 children were analysed:
      30 with Hashimoto's thyroiditis and 38 healthy, age-matched controls, mean age:
      13.6 years. CTLA-4 exon 1 polymorphism (A49G) was defined by the PCR method and
      single-strand conformational polymorphism analysis and confirmed by using BbvI
      enzyme. Statistical analysis was performed using the t- test and Chi-square test.
      RESULTS: Polymorphism analysis showed that statistically significant more
      patients with Hashimoto's thyroiditis were homozygous for G (Ala), and G allele
      frequency was significant higher than in the control group. CONCLUSION: The
      results confirmed the association between CTLA-4 exon 1 polymorphism (A49G) and
      Hashimoto's thyroiditis in polish children.

PMID- 17020649
TI  - [The surface CD152 (CTLA-4) expression on peripheral blood lymphocytes in
      children with Hashimoto's thyroiditis].
AB  - INTRODUCTION: The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a
      transmembrane molecule present on T cells that plays a critical role in the down
      regulation of antigen-activated immune response. Its gene polymorphism is a
      strong candidate gene for conferring susceptibility to thyroid autoimmunity. THE
      AIM of the study was to analyse the surface CTLA-4 (CD 152) expression on
      peripheral blood lymphocytes. MATERIAL AND METHODS: Blood samples from 66
      children were analysed: 36 with Hashimoto's thyroiditis and 30 healthy, age
      matched controls, mean age: 13.4 years. The percentages of peripheral blood
      lymphocyte subsets were analysed by evaluation of CD antigens surface expression
      with three colour flow cytometry using Coulter EPICS XL cytometer. CD28, CD152,
      CD4, CD8 antigens were evaluated. Statistical analysis was performed using t-
      test and other tests of the Statistica programme. P-value <0.05 was considered as
      statistically significant. RESULTS: In children with Hashimoto's thyroiditis the
      surface expression of CD8(+) CD152(+) T cells was statistically significant lower
      than in healthy controls. P-value was 0,02. Percentage of other CD examined in
      the study did not differ significantly in patients and in the control group.
      CONCLUSION: In children with Hashimoto's thyroiditis the surface expression of
      CTLA-4 (CD152) on peripheral blood lymphocytes CD8(+) was statistically
      significantly lower than in healthy controls.

PMID- 17020650
TI  - [Tumor necrosis factor alpha (TNF-alpha) gene G-308A polymorphism relationship to
      insulin resistance and lipid abnormalities in children with obesity].
AB  - INTRODUCTIONS: High levels of tumor necrosis factor (TNF-alpha)-cytokine produced
      by adipocytes, are involved in the development of obesity-related insulin
      resistance and metabolic syndrome. Therefore, we investigated whether the
      polymorphism of TNF-alpha-308 gene can predict the conversion from insulin
      resistance and obesity parameters in children with obesity. THE STUDY comprised
      72 children with obesity simplex (9-18 y.o). The following anthropometric
      parameters: weight, height, BMI, SDS for BMI, WHR, sum of 3, 10 skinfolds and
      percentage of body fat by Slaughter's equation were calculated. In each child,
      after 12 hour overnight fast, glucose, insulin, leptin and lipids: triglycerides
      (Tg), cholesterol total (Chol-T), cholesterol HDL (Chol-HDL), cholesterol LDL
      (Chol-LDL) were measured. The oral glucose tolerance test was performed and HOMA
      IR was calculated. RESULTS: Using the technique of PCR-RELP and SSCP, three
      variants of genotype TNF-alpha were obtained: G/G-68%, A/G-29%, A/A-3%.
      Statistical analysis of anthropometric, biochemical and leptin variables in
      groups G/G, vs. A/G +A/A, in boys and girls was performed. We did not find any
      significant differences between groups (G/G vs. A/G +A/A in all group, and
      between G/G girls, boys vs A/G +A/A girls, boys) Our data indicate that in
      smaller children studies, TNF-alpha polymorphism does not seem not to be
      associated with the degree of obesity and insulin resistance.

PMID- 17020651
TI  - [The influence of polymorphism the Gly972Arg variant insulin receptor substrate-1
      (IRS-1) gene, and G-308A TNF-alpha gene on obesity and insulin resistance in
      children with obesity].
AB  - Genetic factors play a role in the pathogenesis of insulin resistance in obese
      subjects. The insulin receptor substrate-1 (IRS-1) and IRS-2 are the most
      important elements of the insulin-signaling pathways, and mutations in this gene
      have been reported to play a role in determining insulin resistance, particulary
      in presence of obesity. The polymorpism of the TNF-a-308 gene is also involved in
      the development of obesity-related insulin resistance, therefore, we investigated
      whether the IRS-1 and TNF-a polymorphism can predict conversion to insulin
      resistance and obesity parameters in children with obesity. MATERIAL AND METHODS:
      The 70 children with obesity simplex were included in this study (9-18 y.o). The
      antropometric investigations: weight, height, BMI, SDS for BMI, WHR, sum of 3, 10
      skinfolds, and percent of body fat by Slaughter's equation was calculated. In
      each children after 12 hour overnight fast glucose, insulin, leptin and lipids:
      triglycerides (Tg), cholesterol total (Chol-T), cholesterol HDL (Chol-HDL),
      cholesterol LDL (Chol-LDL) were measured. The oral glucose tolerance test was
      performed and HOMA-IR was calculated. RESULTS: Two variants of genotypic IRS-1
      were obtained: C/C(85.7 %), A/C(14.3%), and 3 variants of TNF-a G/G 68 % A/G 29%
      A/A 3%. Statistical analysis of anthropometric and biochemical variables in
      groups C/C, vs A/C and variables between IRS and TNF (G/G, A/G + A/A) groups was
      performed. We did not find any significant differences between these groups in
      the t-Student test. The girls heterozygous for the A allele--A/C (IRS) had higher
      body weight than girls who were homozygous C/C (chi(2) =3.87, Pr>chi(2)=0,048).
      In smaller children studies, both polymorphism--IRS and TNF seems not to be
      associated with the degree of obesity and insulin resistance.

PMID- 17020652
TI  - [Selected matrix metalloproteinases (MMP-2, MMP-9) in obese children and
      adolescents].
AB  - INTRODUCTION: In the last years it has been proved that matrix metalloproteinases
      participate in the development of all stages of atherosclerotic process. It has
      been suggested that plasma levels of metalloproteinases can be a novel,
      inflammatory marker of atherosclerosis. THE AIM OF THE STUDY was to evaluate
      plasma levels of selected matrix metalloproteinases (MMP-2 and MMP-9) in obese
      children and adolescents. MATERIAL AND METHODS: We studied 45 children and
      adolescents with simple obesity aged 15+/-1.8 years. The control group comprised
      28 healthy, slim children aged 14.5 years. The obese children were studied
      according to coexistence of hypertension, hyperlipidemia, positive family history
      of cardiovascular diseases and insulin resistance. Levels of matrix
      metalloproteinases were assessed by use of ready ELISA kits (R&D Systems).
      RESULTS: MMP-9 level in the study group equaled 553.5+/-311 ng/ml and was
      significantly higher compared to the control group: 400.4+/-204 ng/ml, p=0.02.
      MMP-2 level in the study group was significantly lower compared to the control
      group: 211+/-37 ng/ml vs. 258+/-56 ng/ml, p<0,0001. In obese children with
      coexisting hypertension we found higher levels of MMP-9 when compared to children
      with obesity only: 635+/-308 ng/ml vs. 450+/-289 ng/ml (p=0,04), MMP-2 levels
      remained similar in both groups. CONCLUSIONS: Different levels of plasma matrix
      metalloproteinases in obese and hypertensive children compared to healthy, slim
      controls can indicate an altered metabolism of the extracellular matrix (ECM) of
      vessels and heart muscle. Changed metabolism of ECM may be of significant
      importance in enhancing the atherosclerotic process in this young patients.

PMID- 17020653
TI  - [Metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 levels
      in children and adolescents with type 1 diabetes].
AB  - INTRODUCTION: Abnormal activation of the matrix metalloproteinases (MMPs) in
      diabetes mellitus leads to extracellular matrix changes through the structural
      protein composition changes. The metalloproteinases inhibitors (TIMPs) are
      regulatory factors in this activity. Not all regulating mechanisms are completely
      known, especially in patients with type 1 diabetes. THE AIM OF STUDY: evaluation
      of MMP-2, MMP-9 and TIMP-1, TIMP-2 levels in children and adolescents with type 1
      diabetes. MATERIAL AND METHODS: 74 patients in the mean age 15 years (+/-3.0)
      suffering from type 1 diabetes for mean 6.6 years (+/-3.6) took part in the
      study. Patients were treated with flexible multiple daily insulin (n=54) and with
      continuous subcutaneous insulin infusion - personal insulin pump (n=20). MMP-2,
      MMP-9, TIMP-1 and TIMP-2 blood serum levels were measured in all patients. 45
      healthy persons matched for age, without atherosclerosis risk factors, with
      proper BMI and lipids levels were in the control group. RESULTS: MMP-2 level as
      well as TIMP-2 and TIMP-2 levels were significantly higher in patients with type
      1 diabetes in comparison to the control group (p respectively <0,01; <0,02;
      <0,001). We observed higher MMP-9 level in obese patients than in patients with
      BMI value below 90 pc for sex and age (p<0,02). We noted lower MMP-2 level in
      patients with chronic complications and/or arterial hypertension (n=24) in
      comparison to patients without that kind of complications (p<0,05). Positive
      correlation between TIMP-1 level and HbA1c level was noted. Age of patients as
      well as BMI negatively correlated with MMP-2 and TIMP-2 and positively with TIMP
      1. We observed a correlation between MMP-2, TIMP-2 and especially TIMP-1 with
      lipid levels. Strong positive correlation was noted between MMP-2 and TIMP-2
      (r=0.8; p<0,0001). CONCLUSIONS: 1. MMP-2, TIMP-1 and TIMP-2 levels are higher in
      patients with type 1 diabetes than in the control group. 2. Age, diabetes
      duration, metabolic control, BMI and lipids levels have influence on the
      MMPs/TIMPs system. 3. TIMP-1 is supposed to be the key marker of metabolic
      disturbances in type 1 diabetes.

PMID- 17020654
TI  - [The prevalence of thyro-peroxidase antibodies and thyroid function in Turner's
      syndrome].
AB  - INTRODUCTION: Higher frequency of autoimmune diseases in patients with Turner's
      syndrome (TS) compared with the general population has been described. 5 to 10%
      of cases occur before adolescence. The goal of the study was to determine the
      prevalence of thyro-peroxidase antibodies (TPO-Ab) in correlation with karyotype,
      clinical symptoms and hormonal thyroid function in TS patients. MATERIAL AND
      METHODS: 96 girls with TS, aged 0.5-19.8 years (mean age 12.3+/-5.0) and 58 girls
      matched for age and BMI (control group) were analysed. The diagnosis of TS was
      established basing on clinical features and karyotype analysis. 54 had X
      monosomy, 7--isochromosome, 1--other X chromosome aberration, 11--mosaicism
      45,X/46,XX, 3--45,X/47,XXX, 1--45,X/46,XX/47,XXX, 19--mosaicism with structural
      aberration: 12--45,X/46,X,i(Xq), 2--others, 5--with Y chromosome. In all children
      TSH, FT(4), FT(3), TPO-Ab, cholesterol, triglyceride levels, physical and
      ultrasonographic examination were performed. RESULTS: 25% of TS patients were
      positive for TPO-Ab. This frequency was significantly higher (p=0.0017) than that
      seen in the control group (5.2%). Positive titers of TPO-Ab were found: in 42% of
      girls with isochromosome (46,X,i(Xq) and 45,X/46,X,i(Xq)), 22.2% with X monosomy,
      and 17.4% with other karyotypes. The percentage of positive TPO-Ab titres
      increased with cumulative age of TS patients. It was 6.7% at the age of 10 years
      and almost doubled (12.1%) one year later. The next strong increase was observed
      at the age of 16 (up to 19.1%) and gradually rose to 20 years of age. Mean age of
      seronegative patients was significantly lower than that of seropositive patients
      (p=0.018). Only 2 patients manifested symptoms of hyperthyroidism requiring short
      period of antithyroid treatment. Others did not reveal any clinical features of
      thyroid dysfunction, although developed thyroid abnormalities such as elevated
      TSH (11.4%) or goiter (28%). Lack of correlation between TPO-Ab, thyroid hormones
      and lipid levels was associated with L-thyroxine supplementation, in patients
      with mildly elevated TSH, prior to the study. CONCLUSIONS: Patients with TS,
      especially with isochromosome, have antithyroid antibodies more frequently than
      their co-evals. Therefore, it is important to monitor TPO-Ab from about the age
      of 10 years even in asymptomatic patients. However, in routine clinical practice,
      both the thyroid examination and TSH level (even in asymptomatic patients) should
      be screened yearly for early detection of subclinical hypothyroidism and risk of
      more severe growth retardation in girls with TS.

PMID- 17020655
TI  - [Anti-Mullerian hormone (AMH) measurements in the assessment of testicular
      function in prepubertal boys and in sexual differentiation disorders].
AB  - In males AMH is produced by the testes from fetal life to puberty. The main role
      of AMH in the male fetus is to cause Mullerian duct regression, in prepubertal
      boys AMH is involved in testicular development and function. THE AIM OF THIS
      STUDY was to assess the use of a sensitive assay kit of AMH measurements in the
      diagnosis and management of children with abnormal sexual differentiation and
      cryptorchidism. We also compared the serum AMH levels with testosterone levels
      after hCG stimulation. METHODS: We assessed serum AMH levels in 79 prepubertal
      patients: gonadal dysgenesis (n=23), partial androgen insensitivity (n=4),
      scrotal hypospadiasis (n=16), bilateral cryptorchidism (n=20), anorchia (n=10)
      and unilateral cryptorchidism (n=6). Earlier hCG test was performed (one dose of
      2000 IU/m2 i.m.) and testosterone levels were determined. RESULTS: AMH level was
      not impaired in patients with unilateral cryptorchidism and partial androgen
      insensitivity (median 350 pmol/l). AMH was normal in most of boys with scrotal
      hypospadiasis (median 317 pmol/l). Significant differences were observed between
      AMH levels in boys with hypospadias and patients with gonadal dysgenesis (median
      174 pmol/l; p<0,001). In the cryptorchid group AMH level was normal in 50% of
      boys. There was a significant difference between AMH levels in cryptorchid boys
      (median 249.5 pmol/l) and patients with anorchia; (p<0,001). AMH levels were
      almost undetectable in boys with vanishing testes (median 1.0 pmol/l). The basal
      AMH levels were correlated with testosterone response to hCG. CONCLUSIONS: When
      testes are non-palpable a single measurement of serum AMH level can distinguish
      between cryptorchidism and anorchia. AMH determination can help in the diagnosis
      of intersex conditions. Our data demonstrated that basal AMH measurements
      correlate with testosterone response to hCG. Serum AMH concentration in
      prepubertal children is a marker of testicular function. Preoperative measurement
      of AMH can be useful in the management of children with cryptorchidism and
      intersex disorders.

PMID- 17020656
TI  - [Ultrasonographic evaluation of selected parameters of the endothelial function
      in brachial arteries and IMT measurements in carotid arteries in children with
      diabetes type 1 using personal insulin pumps--preliminary report].
AB  - INTRODUCTION: Type 1 diabetes is a known risk factor for arterial
      atherosclerosis. The first symptoms can be found even in childhood. The
      ultrasonographic measurements of intimal plus medial thickness in carotid
      arteries (IMT) and flow mediated dilatation (FMD) evaluated in brachial arteries,
      play a known role in the detection in these cases. The diabetes treatment
      intensification is an important factor in delaying early atherosclerotic changes.
      Currently, intensive treatment of children's diabetes with use of continuous
      subcutaneous insulin infusion with personal insulin pumps is gaining more and
      more popularity. THE AIM OF THIS STUDY was the evaluation of IMT and FMD indexes
      in children suffering from type 1 diabetes in the context of treatment
      intensification (multidose insulin injections v. personal insulin pumps).
      MATERIAL AND METHODS: We examined 64 children (29 boys and 35 girls) in the mean
      age 15.5 years treated with the multidose insulin injections method and 10
      children using personal insulin pumps (4 girls and 6 boys) in the mean age 14.5
      years. Using high resolution ultrasonography we evaluated IMT values in carotid
      arteries and FMD parameters in brachial arteries. In our analysis we estimated
      the blood concentration of lipid parameters, values of systolic and diastolic
      blood pressure, the age of diabetes onset, duration time of the illness and the
      values of HbA1c as a marker of metabolic control. RESULTS: We noticed
      significantly higher FMD values in patients treated with personal insulin pumps
      (13.7 vs. 5.5%, p=0.001). IMT values were similar in both groups (0.52 vs. 0.5
      mm, p=0. 41). The level of HDL cholesterol was higher and triglycerides lower in
      the group with treatment intensification. The metabolic control was the same in
      both groups. In patients treated by the multidose insulin injections IMT
      correlated with systolic blood pressure values. We didn't notice any correlation
      between IMT and FMD in any group. CONCLUSIONS: 1. Treatment intensification
      (personal insulin pumps) influences better vascular endothelial function in type
      1 diabetic children and seems to be a significant tool in delaying the
      atherosclerotic process. 2. We need more examinations to explain the role of
      treatment intensification in common carotid arteries wall morphology in type 1
      diabetic children. 3. The ultrasonographic detection of atherosclerotic changes
      in arterial vessels can help in the evaluation of the changes due to different
      methods of diabetes treatment.

PMID- 17020657
TI  - [Causes of menstrual disorders in adolescent girls--a retrospective study].
AB  - INTRODUCTION: Adolescent girls often visit the outpatient endocrinological clinic
      because of menstrual disorders. The problem arises whether to recognize the
      menstrual cycle irregularity as a physiology of the adolescence or to initiate
      diagnostic procedures to exclude pathology. Although irregular menses during
      first 3 years after menarche are usually symptoms of hypothalamus-pituitary-ovary
      axis immaturity, it does not exclude disorders to be subject of diagnosis and
      treatment. THE AIM OF THE STUDY was to evaluate causes of menstrual disorders in
      adolescent girls, who visited the outpatient clinic of the Department of
      Endocrinology and Diabetology for Children and Adolescents, Wroclaw Medical
      University, between 2001-2005. MATERIAL AND METHODS: The study comprised 76
      patients, who visited the outpatient endocrinological clinic because of menstrual
      disorders. Only the girls at least 2 years after menarche or with amenorrhoea
      primaria were included. The following parameters were analyzed: age, age of
      menarche, height and body mass, BMI, evidences of androgen excess, hormone
      levels, gynecological and ultrasound examination. RESULTS: Average age in the
      examined group was 16.2 years (min 12.5, max 20), average age of menarche was
      12.5 years. Evidence of androgens excess were found in 48 patients (63.2%). The
      girls were coming to the clinic most often because of rare menses, most rarely
      because of primary lack of menstruation. Depending on the type of disorders they
      were divided into five groups: group I--amenorrhoea primaria--4 patients (5.3%),
      group II--amenorrhoea secundaria--14 patients (18.4%), group III--oligomenorrhoea
      -38 patients (50%), group IV--polymenorhea--8 patients (10.5%), group V--mixed
      disorders--12 patients (15.8%). The causes of menstrual disorders depended on the
      group. CONCLUSIONS: 1. Menstruation cycles irregularity in the first years after
      menarche may be a symptom of pathology demanding diagnosis and treatment. 2. PCO
      should be taken into consideration as a frequent cause of menstrual disorders in
      adolescent girls.

PMID- 17020658
TI  - [Estimation of the correlation of insulin resistance and selected adipocytokines
      in children with simple obesity--preliminary study].
AB  - BACKGROUND: Insulin resistance--a key element of the metabolic syndrome--is
      observed in children with simple obesity. Adipose tissue is producing bioactive
      substances called adipocytokines. Some of them may play a role in the development
      of insulin resistance. AIM OF THE STUDY: Estimation of the frequency of insulin
      resistance and its correlation with leptin, adiponectin and resistin levels in
      children with simple obesity. MATERIAL AND METHODS: The 53 children (BMI>97
      centile), mean age 13.57 years. Mean BMI was +4.04 SDS. Oral glucose tolerance
      test (OGTT) was performed. Insulin levels at 0' < or = 15 microIU/mL and/or
      insulin peak during OGTT < or = 150 microIU/mL and/or peak at 120' < or =75
      microIU/mL were established as normal values. Homa ratio was calculated. Patients
      were divided into groups depending on the presence or absence of hyperinsulinemia
      / insulin resistance. Concentrations of adiponectin, leptin, resistin were
      measured. RESULTS: In 13.23 % children various types of hyperglycemia were
      diagnosed and hyperinsulinemia in OGTT was noted in 83.02 %. Severe insulin
      resistance (HOMA>3) was diagnosed in 71.82 %. In the hyperinsulinemia group
      higher glucose levels in OGTT were stated comparing to the non hyperinsulinemia
      group. In children with insulin resistance, higher BMI and SD BMI were observed.
      In this paper results of correlations of adipocytokines levels and anthropometric
      parameters or carbohydrates metabolism in children with / without insulin
      resistance are presented. CONCLUSIONS: In children with severe insulin resistance
      adiponectin concentrations correlate negatively with glucose levels, there is a
      positive correlation of adiponectin and glucose and insulin in a group without
      severe insulin resistance. In patients with insulin resistance leptin
      concentrations correlate positively with the degree of obesity and insulin levels
      in OGTT.

PMID- 17020659
TI  - [Role of apoptosis in autoimmune thyroid disorders].
AB  - Apoptosis, programmed cell death, is a physiological phenomenon, necessary for
      normal function of every organism. This is an active process, per-current with a
      participation of the cellular metabolism embracing the activation of genes and
      the synthesis of proteins. The signal to apoptosis can be started practically in
      every cell of our organism. Disturbances of the apoptosis regulation determine
      the essential link of the pathogenesis of many diseases, including autoimmune
      thyroid disorders. Such molecules as FasL, TNF (tumor necrosis factor), TRAIL
      (the ligand inducing apoptosis), inducing different apoptotic pathway can play
      the key-role in the pathogenesis of Graves' disease or Hashimoto's thyroiditis.
      Besides in the destructive thyroiditis an important role is also played by
      proteins from the bcl-2 family and the proinflammatory cytokines. The aim of this
      publication is to present the influence of different factors on the apoptosis and
      the role of programmed cells death in autoimmune thyroid diseases.

PMID- 17020660
TI  - [Obesity related complications in children and adolescents].
AB  - The epidemic of obesity concerns also children and adolescents. Excess weight
      increases the risk of metabolic complications, diabetes type 2, hypertension,
      cardiovascular disease, pulmonary and musculoskeletal disorders, psychosocial
      problems. Simple obesity leads to secondary endocrine disturbances. Long lasting
      insulin resistance and proinflammatory state induced by cytokines, which are
      produced in adipose tissue, play the main role in the development of obesity
      associated complications. Many disturbances can be reversed at the early stage,
      if even small weight loss is achieved.

PMID- 17020661
TI  - [Is arterial hypertension a significant problem in children and adolescents with
      type 1 diabetes?].
AB  - In the last two decades the problem of arterial hypertension in patients in the
      developmental age gained an increasing interest. The frequency of arterial
      hypertension in children was estimated at the level of 1-5% of the population. It
      was demonstrated that hypertension is observed in patients with type 1 diabetes
      over two-three times more frequently than in the general population. Arterial
      hypertension is a significant risk factor for cardio-vascular complications. The
      coexistence of diabetes type 1 and arterial hypertension predisposes to ischemic
      heart disease, stroke and premature death. Normal range of arterial tension for
      children was established during the Task Force on Blood Pressure Control study in
      children. Models depending on age and sex were created. Measurements above the 95
      percentile for age and sex were referred to as significant hypertension and above
      the 97 percentile as heavy hypertension. For the development of arterial
      hypertension in patients with type 1 diabetes, which is the dominant type in
      children and adolescents, apart from the genetic predisposition, the coexistence
      of nephropathy is important. In children and adolescents almost exclusively
      secondary nephrogenic hypertension is observed, which develops usually 2 years
      after microproteinuria. Seldom in children and adolescents with type 1 diabetes
      essential hypertension or hypertension of other causes, as for example
      contraction of the nephrotic artery, may be observed. A particular form of
      arterial hypertension is lack of pressure decrease during the night, with a
      maintenance of the normal rhythm during the day. Recently the state called "pre
      hypertension", considered as a precursor of hypertension and a predictor of
      excessive cardiovascular risk, has gained increasing interest. The
      pharmacological therapy of arterial hypertension in patients with diabetes type 1
      may be taylored individually, depending on the degree and form of diabetes, and
      also on its late complications. In case of an unfavourable course dialysis may be
      considered and transplantation of the kidney, as hemodialysis in children with
      type 1 diabetes is connected with frequent complications. It is crucial to
      consider the transplantation of the kidney at early stages, when the creatinine
      level is above 5 mg/dl. It has been proved that the results of transplantation in
      patients with diabetes are similar to those in patients without diabetes.

PMID- 17020662
TI  - [Normalisation of contralateral adrenal function after long-term mitotane therapy
      in a girl after surgical treatment of adrenocortical carcinoma].
AB  - The main method of treatment of adrenocortical tumours is surgery. The efficacy
      of the mitotane therapy is still controversial with many serious side effects of
      the therapy. Moreover, patients receiving mitotane should be carefully monitored
      for adrenal insufficiency and usually require long-term hormone replacement
      therapy. We present a rare case of normalisation of the contralateral adrenal
      function after long-term mitotane therapy as a post-surgical treatment of the
      adrenocortical tumour.

PMID- 17020663
TI  - [Is Crohn's disease an indication for growth hormone treatment?].
AB  - In this review we discuss contemporary opinions about the Lesniowski-Crohn
      disease in particular hormonal abnormalities including growth hormone resistance
      and the role of adipocytokines. The place of growth hormone in the treatment of
      chronic inflammatory bowel disease was also discussed.

PMID- 17020664
TI  - Venous thromboembolic disease. Clinical practice guidelines in oncology.

PMID- 17020665
TI  - Risk factors for the assessment of patients with pulmonary embolism.
AB  - Pulmonary embolism (PE) occurs frequently among cancer patients, with a spectrum
      ranging from small, clinically insignificant thrombi to life-threatening massive
      PE. It is fatal in as many as 14% of cancer patients, primarily by producing
      right ventricular heart failure and cardiogenic shock. PE diagnosis is difficult
      because the signs and symptoms imitate other commonly occurring diseases.
      Clinicians must be able to integrate a wide array of diagnostic imaging tools and
      laboratory tests to ensure rapid assessment and diagnosis. Risk stratification
      with the use of cardiac biomarkers and imaging tests to evaluate right
      ventricular function will identify treatment options. Hemodynamically stable
      patients can be treated effectively with anticoagulation alone, whereas those
      with right ventricular dysfunction require an aggressive strategy with
      thrombolysis, surgical embolectomy, or a catheter-based intervention. When
      anticoagulation is contraindicated, a vena caval filter may be deployed. PE
      treatment must be customized to the individual and consider the existing thrombus
      burden, presence of underlying cardiopulmonary disease and right side heart
      dysfunction, and cancer status of the patient. Clinicians should focus on
      providing adequate thromboprophylaxis in hospitalized cancer patients to avoid PE
      treatment.

PMID- 17020666
TI  - Inferior vena cava filters in the cancer patient: current use and indications.
AB  - Deep venous thrombosis and thromboembolism are significant health risks, with
      high rates of morbidity and mortality. Chronically ill and hospitalized patients,
      particularly those with cancer, have a high risk for developing these conditions.
      Mechanical inferior vena cava (IVC) filtration has been standard care for
      patients with these conditions in whom anticoagulation therapy is contraindicated
      or has failed. This article reviews caval filters and the current indications for
      using mechanical IVC filters, including retrievable versus permanent filters,
      focusing on their use in treating venous thromboembolism in cancer patients.

PMID- 17020667
TI  - Catheter-related thrombosis: risks, diagnosis, and management.
AB  - Symptomatic thromboembolic complications of central venous catheters (CVCs) occur
      in 5% or less of general oncology patients. Asymptomatic CVC-related thrombi are
      more common, but their clinical significance is unclear. Thrombotic risk may be
      increased by primary thrombophilic disorders, especially the factor V G1691A
      (Leiden) mutation, thrombogenic catheter material, larger catheter diameter and
      greater number of lumens, catheter tip malposition, left-sided placement,
      percutaneous or multiple insertion attempts, a previous CVC or preexisting venous
      obstruction, prothrombotic therapeutic agents, catheter-associated infections,
      and fibrinous catheter lumen occlusion. Three recent randomized, prospective,
      placebo-controlled trials observed no benefit of routine low-dose warfarin or low
      molecular-weight heparin in preventing catheter-associated thrombosis.
      Nevertheless, thromboprophylaxis may be appropriate and safe for selected high
      risk patients. Duplex ultrasound can accurately detect CVC-related thrombi
      involving the jugular, axillary, distal subclavian, and arm veins. Contrast
      venographic imaging is required for indeterminate duplex findings and to evaluate
      the deep central veins and pulmonary arteries. Therapeutic anticoagulation, with
      or without catheter removal, is indicated for patients with acute deep vein
      thrombosis (DVT) or pulmonary embolism who have no contraindications. Catheter
      removal alone, with close follow-up, may be sufficient when bleeding risk
      precludes safe anticoagulation. Approaches to managing catheter-associated
      thrombosis, including the use of thrombolytic agents, are guided by limited
      published experience and extrapolation from practices used for lower-extremity
      DVT. Prospective, randomized, controlled trials are needed to identify the safest
      and most effective anticoagulant agents, treatment durations, and alternative
      venous access strategies for cancer patients who develop catheter-associated
      thrombosis.

PMID- 17020668
TI  - Long-term therapy of venous thromboembolism in cancer patients.
AB  - Venous thromboembolism (VTE) is a common complication in cancer patients that
      results in significant morbidity and mortality. Long-term treatment options for
      cancer patients who experience VTE include vitamin K antagonists (VKAs), low
      molecular weight heparins (LMWHs), and inferior vena caval (IVC) filters. Cancer
      patients have a two- to fourfold higher risk for experiencing recurrent VTE and
      major bleeding during chronic VKA therapy than patients without malignancies.
      Recent randomized clinical trials have shown that LMWHs rather than oral VKAs are
      preferred for initial chronic treatment of VTE in patients with advanced cancer.
      One factor potentially limiting the broader use of LMWH for chronic therapy in
      the United States is its higher acquisition cost. Efficacy, cost, drug
      availability, patient comorbidities, and concomitant medications all need to be
      considered when selecting chronic VTE therapy. Cancer patients with VTE should be
      treated for as long as their disease is active to minimize the incidence of
      recurrence. Use of IVC filters should generally be reserved for patients at high
      risk for recurrent VTE who have contraindications to anticoagulation. Several new
      anticoagulants are being investigated that promise greater therapeutic choices
      and potentially better outcomes for cancer patients with VTE.

PMID- 17020669
TI  - Ovarian cancer. Clinical practice guidelines in oncology.

PMID- 17020670
TI  - Intraperitoneal chemotherapy for ovarian cancer: where are we now?
AB  - Patients with advanced epithelial ovarian cancer are conventionally treated with
      intravenous (IV) platinum- and taxane-based chemotherapy to try to eradicate
      residual disease after optimal cytoreductive surgery, resulting in a median
      overall survival of 49 months. The Gynecologic Oncology Group (GOG) conducted 3
      large randomized, phase III clinical trials of intraperitoneal (IP) chemotherapy
      (GOG 104, 114, and 172) that clearly showed superior progression-free and overall
      survival with IP chemotherapy compared with IV chemotherapy. All 3 clinical
      trials investigated IP cisplatin, with the last one adding IP paclitaxel. The
      most recent study (GOG 172) resulted in a median survival of 66 months for
      patients in the IP arm versus 50 months for those in the IV arm. Fewer patients
      in the IP arm than in the IV arm completed all 6 treatment cycles (42% vs. 83%,
      respectively) because of the toxic effects of chemotherapy and IP catheter
      related complications. Initially, patients in the IP arm reported significantly
      worse quality of life than those in the IV arm. However, at 12-month follow-up,
      the groups experienced no difference in quality of life, except that paresthesias
      were more likely to persist at moderate levels among patients in the IP arm.
      Based on these clinical trials, the National Cancer Institute issued a clinical
      announcement recommending that women with stage III ovarian cancer who undergo
      optimal surgical cytoreduction be considered for IP chemotherapy.

PMID- 17020671
TI  - Rational use of cytotoxic chemotherapy for recurrent ovarian cancer.
AB  - Ovarian cancer remains the leading cause of death among women with gynecologic
      malignancies, and the fifth leading cause of cancer mortality in women in the
      United States. Although many patients respond to first-line platinum-based
      therapy, most will experience disease recurrence. The role of further therapy in
      the setting of recurrent ovarian cancer is palliative, and large randomized phase
      III trials on treatment options for recurrent ovarian cancer are rare.
      Controversies exist as to the optimal timing and duration of treatment, and many
      issues regarding treatment of recurrent disease remain.

PMID- 17020672
TI  - Novel non-cytotoxic therapy in ovarian cancer: current status and future
      prospects.
AB  - Although significant improvements in standard therapy for ovarian carcinoma have
      been made over the past decade, current treatment is limited by the development
      of resistance to cytotoxic chemotherapy, and most women ultimately die of the
      disease. New knowledge of the biology of ovarian cancer has led to the
      identification of potential molecular targets that are differentially expressed
      in normal cells versus cancer cells, and advances in pharmacology have led to the
      development of novel agents that work differently from traditional cytotoxic
      chemotherapy by exploiting these targets. Many of these agents are being
      evaluated in clinical trials. This article discusses molecular targets that are
      important in ovarian carcinoma, including angiogenesis, tyrosine kinases, mitogen
      activated protein kinases, and phosphatidylinositol-like kinases such as
      mammalian target of rapamycin, and the proteosome. This article reviews novel non
      cytotoxic agents that target these pathways and are currently being evaluated in
      ovarian carcinoma treatment.

PMID- 17020673
TI  - [Presentation].

PMID- 17020675
TI  - [Implantation of a hospital registry of hereditary nonpolyposis colorectal
      cancer].
AB  - INTRODUCTION: Identification of patients with hereditary nonpolyposis colorectal
      cancer (HNPCC) can allow colorectal cancer (CRC) prevention through colonoscopy
      and polypectomies. The purpose of this study was to report the clinical
      characteristics of HNPCC families in our registry. PATIENTS AND METHOD: HNPCC was
      identified using the Amsterdam criteria. Familial clustering of CRC and
      extracolonic cancers were investigated in families. Individuals at risk were
      offered annual colonoscopy, starting from the age of 25 years. RESULTS: Twelve
      HNPCC families were identified. There were 46 cases of CRC in 38 patients. The
      mean age at diagnosis of CRC was 45.4 +/- 12.7 years (range 25-73 years). In
      patients with documented disease, right-sided tumors predominated. Eleven
      patients with extracolonic cancer were identified (six tumors located in the
      endometrium). Of 43 at-risk individuals, 29 accepted surveillance. CONCLUSIONS:
      Our data confirm the importance of the family history in identifying HNPCC. This
      study confirms previously described characteristics in HNPCC, namely, early age
      at onset of CRC, right-sided predominance, multiple synchronous and metachronous
      neoplasms, and increased extracolonic cancers. This is the first study of
      clinical data in a Spanish HNPCC registry.

PMID- 17020674
TI  - [The "Seville" Consensus Document on Alternatives to Allogenic Blood Transfusion.
      Sociedades espanolas de Anestesiologia (SEDAR), Medicina Intensiva (SEMICYUC),
      Hematologia y Hemoterapia (AEHH), Transfusion sanguinea (SETS) Trombosis y
      Hemostasia (SETH)].
AB  - The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has
      been drawn up by a panel of experts from 5 scientific societies. The Spanish
      Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units
      (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and
      Thrombosis and Hemostasis (SETH) have sponsored and participated in this
      Consensus Document. Alternatives to blood transfusion have been divided into
      pharmacological and non-pharmacological, with 4 modules and 12 topics. The main
      objective variable was the reduction of allogenic blood transfusions and/or the
      number of transfused patients. The extent to which this objective was achieved by
      each AABT was evaluated using the Delphi method, which classifies the grade of
      recommendation from A (supported by controlled studies) to E (non-controlled
      studies and expert opinion). The experts concluded that most of the indications
      for AABT were based on middle or low grades of recommendation, "C", "D", or "E",
      thus indicating the need for further controlled studies.

PMID- 17020676
TI  - [Liver biopsy in patients with chronic hepatitis C virus infection: experience in
      a district hospital].
AB  - INTRODUCTION: Liver biopsy is a highly useful tool in the evaluation of patients
      with chronic hepatitis C. However, the technique is not free of complications and
      presents a series of limitations (lack of representativity and interobserver
      variability in sample interpretation). Due to these limitations and the
      development of new noninvasive techniques, the role of liver biopsy is currently
      being reevaluated. MATERIAL AND METHOD: We performed a descriptive retrospective
      study of liver biopsies performed in patients with chronic hepatitis C virus
      (HCV) infection from January 2002 to January 2005. Age, gender, genotype,
      histology of the hepatic cylinder, and the percentage of patients who received
      treatment after liver biopsy was analyzed. The indications for biopsy in our
      patients and the reasons for nontreatment after biopsy were identified. We also
      analyzed whether the decision to start treatment was influenced by the
      histological grade of the lesion and whether there is any association between
      histological grade and transaminase levels. RESULTS: A total of 156 patients were
      included and 72% received treatment after biopsy. Transaminase levels were
      elevated in 86%. Alanine aminotransferase (ALT) levels were elevated in 92.30% of
      treated patients and in 66% of untreated patients. The most frequent cause of
      nontreatment after biopsy was fibrosis stage < 2. The histological results were
      as follows: G0 in 2%, G1 in 26.8%, G2 in 47.7%, G3 in 22.2% and G4 in 1.3%; stage
      of fibrosis was F0 in 7.2%, F1 in 30.1%, F2 in 37.9%, F3 in 19.6%, and F4 in
      5.2%. Fibrosis was advanced (F >= 2) in 41% of the patients with normal ALT
      levels and was mild (< F2) in 33% of those with elevated ALT levels. CONCLUSION:
      Liver biopsy could be useful in patients with indication for treatment but a high
      risk of treatment-related adverse effects, as well as in those with normal
      transaminase levels, in whom the degree of fibrosis observed could influence the
      therapeutic approach.

PMID- 17020677
TI  - [Gastrointestinal stromal tumors presenting as pelvic masses].
AB  - Gastrointestinal stromal tumors (GIST) appear in the abdominal cavity in less
      than 5% of patients. We present two cases of extraintestinal GIST attended in our
      service and treated with imatinib mesylate. We review the current treatment of
      these neoplasms with targeted therapies.

PMID- 17020678
TI  - [Persistent acute hepatitis in a patient with chronic hepatitis C].
AB  - We describe the case of a patient with chronic hepatitis C (CHC) who showed a
      progressive increase in aminotransferase level, reaching values of aspartate
      aminotransferase 1723 UI/L, alanine aminotransferase 1519 UI/L and gamma-glutamyl
      transpeptidase 296 with a bilirubin level of 6 mg/dL and direct bilirubin level
      of 4.6 mg/dL. One year previously, the patient had been diagnosed with CHC,
      genotype 1, and had an initial hepatitis C virus RNA load of 249,000 UI/mL. All
      the specific blood tests performed were negative except for antisoluble liver
      antigen (anti-SLA) antibodies, which were positive in two different
      determinations. A diagnosis of overlap syndrome CHC and autoimmune hepatitis was
      made. Steroid and azathioprine treatment was started with good response. The
      relationship between CHC and anti-SLA is not well characterized but has been
      described in these patients. We found no prior reports in the literature of CHC
      associated with positive anti-SLA in a patient with persistent acute hepatitis.

PMID- 17020679
TI  - [Approach to thoracic pain from the gastroenterologist's point of view].
AB  - Chest pain is common in medical consultations. One of the most frequent and
      serious causes is acute ischemic heart disease, which must be ruled out. The gold
      standard is coronary angiography. Noncardiac recurrent chest pain has a favorable
      prognosis. The most frequent cause is esophageal disease, with a prevalence of
      between 20% and 50%. The most frequent form is gastroesophageal reflux disease
      followed by esophageal motor disorders. Empirical treatment with high-dose proton
      pump inhibitors should be considered as a diagnostic-therapeutic test before
      performing exhaustive complementary investigations of esophageal function. Among
      complementary tests, manometry combined with 24-hour pH-metry has the highest
      diagnostic yield. Antidepressants are an acceptable therapeutic option in
      patients with esophageal visceral hyperalgesia.

PMID- 17020680
TI  - [Caroli's disease].

PMID- 17020681
TI  - [Clinical practice guideline for irritable bowel syndrome].

PMID- 17020682
TI  - [Fragility non-spinal fractures in a cohort of 5,201 women aged 65 years and
      older during a 3-year follow-up].
AB  - BACKGROUND AND OBJECTIVE: Low-trauma non-spinal fractures are a growing source of
      morbidity and mortality in the elderly. We aimed to evaluate the overall
      incidence of low-trauma non-spinal fractures and of the main skeletal sites in a
      cohort of women from Spain. PATIENTS AND METHOD: A total of 5,201 women, aged 65
      or older, were enrolled in a 3-year cohort study by non-probabilistic sampling of
      consecutive cases in 58 primary care centers in Spain, with 6-month visits. All
      radiological or surgically confirmed low trauma non-spinal fractures were
      collected. RESULTS: 311 women (6.0%) sustained a total of 363 fractures after a
      3.01-year median follow-up, and 14,999 women-year. The incidence rate of overall
      non-spinal fractures was 2,420 cases per 100,000 women-year. The incidence rates
      of hip, forearm and humeral fractures were 887,369 and 333 cases/100,000 women
      year respectively. CONCLUSIONS: Low-trauma non-spinal fractures are highly
      incident in Spain in women aged 65 years or older, similar to other western
      countries.

PMID- 17020683
TI  - [Factors related to the risk of thrombosis in patients with lupus and
      antiphospholipid antibodies].
AB  - BACKGROUND AND OBJECTIVE: Antiphospholipid antibodies (aPL) are frequently
      associated with eritematosus systemic lupus (SLE) and increases the risk of
      thrombosis. The aim of the study was to analize risk factors of thrombosis and
      its temporal profile in subjects with SLE. PATIENTS AND METHOD: One hundred and
      two SLE patients -mean age: 37.5 years (range: 8-85); 90 women; mean of follow
      up: 72 months (range: 9-324); 41 (40.2%) with aPL positive- were included in the
      study. Actuarial Kaplan-Meier curves were used to assess the thrombosis risk and
      Cox proportional hazard model was used to evaluate factors associated with the
      risk. RESULTS: 13 thrombotic events occurred in the group with aPL positive (mean
      of follow up: 83.5 months) and 5 events in aPL negative group (mean of follow up:
      72 months). The event-rates were 3.93 and 0.96/100 patients/year for each group,
      respectively. Survival curves showed a significantly higher risk of thrombotic
      events in the patients with positive aPL as compared to the aPL negative group,
      and the risk still present throughout the observational time. Activated partial
      thromboplastine time up to 37 s was significantly associated with thrombosis risk
      (p = 0.003). Furthermore, positivity of lupus anticoagulant and proteinuria > 2.5
      g/day tended to increase thrombotic risk, although they did not achieve
      statistical significance. CONCLUSIONS: In patients with SLE and aPL, risk of
      first thrombosis remains over the years, and a large activated partial
      thromboplastine time was the most important risk factor.

PMID- 17020684
TI  - [Comparison between phlebotomy and erythrocytapheresis of iron overload in
      patients with HFE gene mutations].
AB  - BACKGROUND AND OBJECTIVE: Large-volume erythrocytapheresis (EA) is an useful and
      speedy method to treat iron overload (IO). We assesed the efficacy of EA in
      patients with HFE gene mutations and IO compared to the classical phlebotomies.
      PATIENTS AND METHOD: Data from 9 patients with IO treated with EA, using a
      discontinuous flow cell separator as a single needle procedure, for a period of 2
      years, were compared to 9 matched patients who underwent conventional
      phlebotomies. RESULTS: The mean volume of red blood cells removed in each EA was
      275 ml, with a median reduction of 23 g/l for haemoglobin and 55 microg/l for
      serum ferritin levels (vs. 17 microg/l between phlebotomies). The liver function
      test returned to normal values in 4 out of 5 patients undergoing EA, but none of
      the phlebotomies. The time required to achieve iron depletion was 3 times shorter
      in EA group. CONCLUSIONS: EA is an effective and safe procedure that achieves
      iron depletion more quickly than manual phlebotomies. Nevertheless, to determine
      its cost-effectiveness, economical, prospective, randomized studies are
      warranted.

PMID- 17020685
TI  - [Osteoporotic fractures in Spanish women].

PMID- 17020686
TI  - [Review of the scientific evidence of the efficiency of erythropoietin use].

PMID- 17020687
TI  - [The last phase in the progressive neoplasic disease: care at the end-of-life,
      refractory symptoms and sedation].
AB  - End-of-life is one of the most stressful phases during course of a neoplasic
      disease. Frequently, death of patients with cancer comes after a continuous and
      progressive physical impairment. As death approaches, the medical team might
      redefine outcomes and treat as priority symptoms and relief suffering. That care
      encompasses the physical, psychological, social, spiritual, and existential needs
      of patients and their families. However, symptoms are frequently observed that
      are intolerable for the patient and which do not respond to usual palliative
      measures. The intolerable nature and being refractory to treatment indicates to
      the health-care team, on many occasions, the need for sedation of the patient.
      The medical team can take comfort in the knowledge that they did their best to
      provide safe passage to all their patients and that, although they did not always
      cure them, the patients often were healed.

PMID- 17020688
TI  - [Cervical pain and neurological symptoms in upper limbs in a 52-year-old man].

PMID- 17020689
TI  - [High incidence of type 1 diabetes in children under age 14 in Almeria, Spain,
      2001-2005].

PMID- 17020690
TI  - [Salmonella serotype Mbandaka food-borne outbreak].

PMID- 17020691
TI  - [TAFI plasma levels are not increased in patients with venous thromboembolic
      disease and factor V Leiden or prothrombin 20210A mutations].

PMID- 17020693
TI  - [Erroneus troponin T determination in immune diseases].

PMID- 17020692
TI  - [Pulmonary leukostasis as a first manifestation of an acute myeloid leukemia
      without hyperleukocitosis].

PMID- 17020694
TI  - [Pseodotumoral central nervous system vasculitis in rheumatoid arthritis].

PMID- 17020695
TI  - [Pancytopenia and acquired factor IX deficiency in patient with Sheehan's
      syndrome].

PMID- 17020696
TI  - [Time, space and frequency in ventricular fibrillation].

PMID- 17020697
TI  - [Intravascular ultrasound volumetric quantification: the current "gold standard"
      for characterization of coronary artery disease].

PMID- 17020698
TI  - [Cost-effectiveness of drug-eluting stents: implications for clinical practice
      and healthcare costs].

PMID- 17020699
TI  - [Time-frequency analysis of ventricular fibrillation. An experimental study].
AB  - INTRODUCTION AND OBJECTIVES: The analysis of frequency variability during
      ventricular fibrillation has yielded inconsistent results. We used an
      experimental model of ventricular fibrillation, with a short timescale, to
      analyze variations in frequency and their associated spatial distribution.
      METHODS: Epicardial recordings of ventricular fibrillation were made in 10
      perfused isolated rabbit heart preparations using a multiple electrode system
      (i.e., 240 unipolar electrodes). Both spectral and time-frequency analysis were
      used to derive the dominant frequency in the anterolateral wall of the left
      ventricle. RESULTS: Linear regression analysis showed that there was a good
      correlation between the dominant frequency obtained using the two signal analysis
      methods: frequency (spectral analysis) = 1.01 x frequency (time-frequency
      analysis) -- 0.4 (r=0.9; P< .0001; standard error of the estimate, 2.2 Hz). In
      all cases except one, the dominant frequency exhibited a significant temporal
      variation on a short timescale (time-frequency analysis); the coefficient of
      variation was between 0.19 (0.06) and 0.24 (0.07) (NS). In all cases, there were
      significant differences between regions. The location at which the frequency was
      highest varied according to the timepoint considered, though it was predominantly
      in the apical or anterior zone. CONCLUSIONS: In the absence of external
      modulating factors, the frequency of ventricular fibrillation exhibits temporal
      and spatial variations which can be observed at short timescales. In the free
      wall of the left ventricle, the dominant frequency is highest in the apical and
      anterior zones, and the maximum frequencies are most often found in these zones.

PMID- 17020700
TI  - [Development of software for three-dimensional reconstruction and automatic
      quantification of intravascular ultrasound images. Initial experience].
AB  - INTRODUCTION AND OBJECTIVES: Quantification of intravascular ultrasound (IVUS)
      images is essential in ischemic heart disease and interventional cardiology.
      Manual analysis is very slow and expensive. We describe an automated computerized
      method of analysis that requires only minimal initial input from a specialist.
      METHODS: This study was carried out by interventional cardiologists and
      biomedical engineers working in close collaboration. We developed software in
      which it was necessary only to identify the media-adventitia boundary in a few
      images taken from the whole sequence. A three-dimensional reconstruction was then
      generated from each sequence, from which measurements of areas and volumes could
      be derived automatically. In total, 2300 randomly selected images from video
      sequences of 11 patients were analyzed. RESULTS: Results obtained using the
      proposed method differed only minimally from those obtained with the manual
      method: for vessel area measurements, the variability was 0.08 (0.07) (mean
      absolute error [standard deviation] normalized to the actual value; this
      corresponds to an error of 0.08 mm(2) per mm(2) of vessel area); for lumen area,
      0.11 (0.11) (normalized), and for plaque volume, 0.5 (0.3) (normalized). Regions
      with severe lesions (<4 mm(2)) were correctly identified in more than 90% of
      cases. Specialist time needed for each reconstruction was 10 (8) minutes (vs 60
      [10] minutes for manual analysis; P< .0001). CONCLUSIONS: The computerized method
      used dramatically reduced the time and effort needed for IVUS sequence analysis,
      and the automated measurements obtained were very promising.

PMID- 17020701
TI  - [Economic impact of the taxus coronary stent: implications for the Spanish
      healthcare system].
AB  - INTRODUCTION AND OBJECTIVES: This article examines the cost impact associated
      with the utilization of the Taxus drug eluting stent versus a conventional bare
      metal stent for percutaneous coronary interventions in a Spanish hospital
      setting. METHODS: A decision analysis model has been developed to compare the
      intervention and re-hospitalization costs at 12 and 24 months post-intervention.
      The analysis considers the general patient population and a high-risk
      subpopulation (diabetes, small vessel, long lesion). The analysis simulates the
      results of the TAXUS-IV clinical trial, in a population with similar risks, with
      appropriate costs, and including budget impact analyses with alternative
      utilization scenarios. RESULTS: The expected average per patient hospital cost at
      12 months was 6934 euros with Taxus and 6756 euros with bare-metal stent (and
      increase of 2.6%). At 24 months, per patient hospital cost was 6,991 euros for
      Taxus and 6887 euros for bare-metal stent (an increase of 1.5%). In the high-risk
      subpopulation, Taxus was overall cost saving as compared to bare-metal stent both
      at 12 months (decrease of 3.0%) and 24 months (decrease of 4.7%). CONCLUSIONS:
      Use of Taxus in the overall population slightly raises treatment costs, while in
      patients with greater risk of restenosis the treatment cost is reduced. Given the
      decrease in the number of repeat revascularizations with this stent, the cost
      effectiveness relationship could be acceptable in the general patient population
      and is dominant in the high-risk subpopulation.

PMID- 17020702
TI  - [Safety and effectiveness of single-lead VDD pacing].
AB  - INTRODUCTION AND OBJECTIVES: Single-lead VDD pacing provides the physiological
      benefits of atrioventricular synchrony with the convenience of a single-lead
      system. However, concern remains about the method's safety and effectiveness.
      METHOD: In total, 700 patients with single-lead VDD pacemakers were evaluated
      retrospectively. The following parameters were recorded: age, sex, etiology, the
      symptoms and electrocardiographic diagnosis that justified pacemaker
      implantation, the venous access route used for implantation, atrial sensing at
      implantation, atrial undersensing at follow-up, the occurrence of
      supraventricular tachyarrhythmias, and final pacing mode. RESULTS: Third-degree
      atrioventricular block was the main indication for pacemaker implantation
      (66.4%). The most commonly used venous access route was via the right cephalic
      vein (49.1%). At implantation, the mean atrial signal was 1.8 (4 1.15) mV. During
      follow-up, significant atrial undersensing occurred in 7.7% of patients; in 1.9%,
      it could not be corrected by device reprogramming. Uncontrollable
      supraventricular arrhythmias were observed in 6.4% of patients. Symptomatic sinus
      node disease was rare. By the end of follow-up, 91.4% of patients were still on
      VDD pacing, while, in 8.3%, the pacemaker had to be reprogrammed to the VVI mode.
      Only 0.3% required atrial lead implantation for DDD pacing. Left-side venous
      access during implantation was a independent predictora of atrial undersensing at
      follow-up. Low values of atrial detection at implant did not reach statistical
      signification although it showed a remarkable trend. CONCLUSIONS: Single-lead VDD
      pacing seems to be safe and effective when appropriately indicated. Our findings
      are consistent with those of previously published studies.

PMID- 17020703
TI  - [Prognostic value of serial measurements of left ventricular function and
      exercise performance in chronic heart failure].
AB  - INTRODUCTION AND OBJECTIVES: The prognostic value of a single measurement of
      ejection fraction and peak oxygen uptake in chronic heart failure has been
      extensively investigated. The aim of our study was to evaluate the prognostic
      significance of serial changes in ejection fraction and exercise performance in
      moderate to severe chronic heart failure. METHODS: 182 patients (156 men, 53 [47
      58] years) underwent echocardiography and cardiopulmonary exercise testing at
      baseline and after 10 [8-12] months. Most patients had idiopathic dilated
      cardiomyopathy (69%) and all patients presented left ventricular ejection
      fraction <45%. Median follow-up was 21 [14-34] months; cardiac death and heart
      transplantation were the end-points. Hazard ratio (HR, per unit) is presented
      with its 95% confidence interval (CI). RESULTS: During follow-up 18 patients
      (9.9%) died and 14 (7.7%) underwent heart transplantation. Baseline ejection
      fraction (HR, 0.94, 95% CI, 0.89-0.98 P=.006) and mitral regurgitation (HR, 4.22,
      95% CI, 1.63-10.92, P=.003), and delta (second examination-baseline) ejection
      fraction (HR, 0.93, 95% CI, 0.88-0.98, P=.01) were the only significant variables
      at univariate analysis. Both ejection fraction and delta ejection fraction
      remained independently associated with events at multivariate analysis. The
      prognostic power significantly increased between a model including ejection
      fraction alone and another one including ejection fraction plus delta ejection
      fraction. CONCLUSIONS: In clinically stable patients with chronic heart failure,
      ejection fraction and its changes were independently associated with outcome; on
      the contrary, serial cardiopulmonary exercise testing did not provide significant
      prognostic value. Baseline plus changes in ejection fraction showed better
      prognostic performance than baseline ejection fraction alone.

PMID- 17020704
TI  - [Myocardial remodeling and immunologic activation in patients with heart
      failure].
AB  - INTRODUCTION AND OBJECTIVES: Immune response-mediated regulation of myocardial
      collagen remains poorly understood. Our objective was to investigate the
      relationship between ventricular remodeling and immunologic activation in
      patients with heart failure (HF) by comparing dilated and ischemic
      cardiomyopathy. METHODS: We studied 94 patients with HF and dilated
      cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left
      ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations
      of tumor necrosis factor alpha (TNFalpha), soluble TNFa receptor I (sTNF-RI),
      sTNF-RII, interleukin-6 (IL-6) and IL-10 were measured. The serum procollagen
      type-III amino-terminal propeptide (PIIINP) level was also obtained. RESULTS:
      Ventricular volumes were greater in the dilated cardiomyopathy than in the
      ischemic cardiomyopathy group (P< .05). However, sTNF-RI, sTNF-RII and PIIINP
      levels were higher in the ischemic group (P< .05). In this group, there were
      significant correlations between ventricular volumes and IL-10 and sTNF-RII
      levels. There was also a significant correlation between PIIINP and sTNF-RII
      levels (r=0.30; P< .05). In the dilated cardiomyopathy group, there was a
      significant correlation between ventricular volumes and IL-10 level, and between
      PIIINP level and IL-6 (r=0.32; P< .05) and sTNF-RII levels (r=0.32; P< .05).
      Multiple linear regression analysis, which included cytokine levels, age, sex and
      ventricular function, showed that the sTNF-RII level was an independent predictor
      of the PIIINP level (adjusted r(2)=0.16; P< .0001) and of ventricular volumes (LV
      end-systolic volume index, adjusted r(2)=0.034; P< .05; and LV end-diastolic
      volume index, adjusted r(2)=.048; P< .05) in both groups. CONCLUSIONS: In HF,
      there is an interaction between proinflammatory cytokines and the extracellular
      matrix. Immunologic implications vary according to disease etiology. The
      elevation in proinflammatory cytokine and PIIINP levels is greater in patients
      with ischemic cardiomyopathy. Multiple regression analysis showed that the sTNF
      RII level was an independent predictor of ventricular remodeling.

PMID- 17020705
TI  - [Pregnancy and heart disease].
AB  - Pregnancy and delivery are associated with substantial physiological changes that
      require adaptations in the cardiovascular system. These changes, well-tolerated
      in pregnant women without heart disease, expose woman with cardiovascular disease
      to serious risk. In fact, heart disease is the most frequent cause of maternal
      death, after psychiatric disorders, and the number of pregnant women with heart
      disease is expected to grow in the coming years. Preventing cardiovascular
      complications should be the main aim of every cardiologist involved in managing
      pregnant woman with congenital or acquired heart disease. Unfortunately, there is
      a lack of data which would help in the management of these patients during
      pregnancy and the clinical practice guidelines are often based on assumptions
      regarding how a specific substrate is going to respond to the physiological
      changes occurring due to pregnancy.

PMID- 17020706
TI  - [The double ring: a new technique for mitral repair].

PMID- 17020707
TI  - [Family medicine and emergency medicine: We continue together].

PMID- 17020708
TI  - [The secondary prevention of ischaemic heart disease in Spain. A systematic
      review of observational studies].
AB  - OBJECTIVE: To describe the use of ischaemic heart disease (IHD) secondary
      prevention measures in the Spanish National Health System. DESIGN: Systematic
      review of observational studies with information on the use of preventive
      treatment and measures in the prevention of secondary IHD. SETTING: Primary care
      and specialised out-patient clinics. DATA SOURCES: Medline search and
      complementary searches of studies published between 1995 and 2004 with a
      description of the use secondary prevention measures on hospital discharge or in
      the follow up after discharge. SELECTION OF STUDIES: A total of 125 references
      were found after the MEDLINE search, 13 of which were selected after an
      independent review by 2 researchers. The complementary sources provided 9 more
      studies giving a total of 22. DATA EXTRACTION: One researcher extracted
      information on the characteristics of the study and the results variables, which
      were independently verified by a second evaluator. RESULTS. In the 22 studies
      found, a high level of variation was shown in the different treatment rates: anti
      aggregants (at discharge, 72%-97.1%; follow-up, 46.4%-93.8%); beta-blockers (at
      discharge, 29%-68.3%; follow-up, 22.4%-59.0%); drugs with action on the renin
      angiotensin system (at discharge, 16.2%-52.2%; follow-up, 6.1%-53.1%); lipid
      lowering drugs (at discharge, 6.7%-88.7%; follow-up, 24.5%-89.5%). The treatment
      rates showed a progressive improvement over time during the period studied.
      CONCLUSIONS: In the period 1994-2003 treatment rates in the secondary prevention
      of IHD have increased, although there is still much room for improvement.

PMID- 17020709
TI  - [Secondary prevention of ischaemic cardiopathy in Spain. Quo vadis?].

PMID- 17020710
TI  - [Study of flu costs].
AB  - OBJECTIVE: To evaluate the costs of influenza epidemics in Spanish society.
      DESIGN: Observational, longitudinal, and multi-centre study of healthcare and non
      healthcare resource use associated with flu. SETTING: Two primary care centres, 3
      hospital emergency services, and the medical service at an old people's home.
      PARTICIPANTS: A total of 662 individuals diagnosed with flu who attended MAIN
      MEASUREMENTS: Direct and indirect costs of flu in Spanish society. RESULTS: The
      60.7% of diagnosed cases of flu included in the study came from hospital
      emergency services, 36.9% from primary health care centres, and 2.4% from an old
      people's home. During the epidemic period, flu in Spain costs about 1036.9
      million euros, taking incidence at 7.9%. Flu-derived costs are higher in over-65
      and chronic patients. CONCLUSIONS: Influenza costs fall mainly on hospitals and
      work through time off. The cost of flu is higher among patients considered to be
      risk groups.

PMID- 17020711
TI  - [Questionnaire to evaluate health web sites according to European criteria].
AB  - OBJECTIVES: To design a questionnaire to evaluate compliance with quality
      criteria on health web sites and to analyse its reliability. DESIGN: A
      descriptive study on the reliability of a questionnaire. PARTICIPANTS: Twenty web
      sites on health topics. SETTING: Internet. MAIN MEASUREMENTS: The questionnaire
      was based on analysis of content of the criteria of the e-Europe 2002 code of
      conduct, comparing these with the criteria underlying the AMA, the Summit code
      and the e-Health Code of Ethics regulations and current directives. The
      dimensions studied were transparency, absence of conflicts of interest,
      authorship, data protection, updating, accountability, and accessibility. A
      preliminary questionnaire was drawn up for a pilot test conducted by 3
      researchers for 20 web sites, its reliability was appraised, adjustments were
      made and the definitive questionnaire was designed. Reliability was evaluated
      again for 26 web sites evaluated by 3 researchers. To evaluate concordance in the
      answers of the participants, Cohen's Kappa index with a 95% confidence level was
      used. RESULTS: All the quality directives of e-Europe 2002, the European
      regulations and relevant points from other questionnaires were included in the
      questionnaire designed. Reliability was acceptable (kappa > or = 0.60) for 12 of
      the 18 quality criteria included. The least concordant aspects of the
      questionnaire were information update (kappa = 0.310) and accessibility (search
      for contents and access for persons with disability). CONCLUSIONS: Reliability of
      the questionnaire designed was acceptable.

PMID- 17020712
TI  - [Comparative study at 4 health centres of efficiency, measured on the basis of
      ambulatory care groups].
AB  - OBJECTIVE: To measure efficiency in the use of resources for the care lists of
      four primary care centres (PCC), by using ambulatory care Groups (ACGs). DESIGN:
      Retrospective, observational study. SETTING: Four PC teams. PARTICIPANTS: All
      patients attended during 2003. MEASUREMENTS: Dependent variables (costs per
      patient, between medical lists [family medicine, paediatrics] and PCCs) and case
      load variables. The model of costs for each patient was set by differentiating
      the semi-fixed and variable costs. The efficiency index (EI) was set as the
      quotient between the observed real cost and the expected cost on the basis of ACG
      distribution, by indirect standardization. The study population was 62,311
      patients seen, with an average of 4.8+/-3.2 episodes/patient/year. MAIN RESULTS:
      The total health care cost reached 24,135,236.62 euro, of which 65.2% was for
      prescription, 28.9% for semi-fixed costs, and 2.9% for cost of specialist
      referrals. The average total cost per patient/year was 387.34 euro+/-145.87 euro
      (average relative weight). The EI for each centre was: 0.93 (95% CI, 0.85-1.01),
      0.97 (95% CI, 0.89-1.05), 1.04 (95% CI, 0.96-1.12), and 1.05 (95% CI, 0.97-1.13),
      P < .0001. In addition, differences between the medical lists (rank, 0.63-1.56)
      and between the paediatrics lists (rank, 0.73-1.26) were found (P = .005).
      CONCLUSIONS: The ACGs enabled us to estimate the efficiency of our PCCs and care
      lists. Efficiency cannot be isolated from other dimensions of the quality of
      health care delivery. Study of the EI improved our understanding of the profile
      of professionals and health centres.

PMID- 17020713
TI  - [Evaluation and improvement in the quality of the program of preventive
      activities and health promotion].
AB  - OBJECTIVE: To confirm that the use of the programme of preventive activities and
      health promotion (PPAHP) for adults in a health district has improved over time.
      DESIGN: Retrospective and transversal descriptive study. SETTING: Primary care,
      Molina la Ribera Health District, Murcia, Spain. PATIENTS AND PARTICIPANTS: The
      target population was the health district s patients between 18 and 79 years old
      seen during the 2 periods of study: 16,236 from 1-05-1995 to 30-04-1996 and
      17,377 from 1-07-2003 to 30-06-2004. Randomised sampling stratified for age and
      sex of the clinical records of the target population gave these samples: 140 at
      the first evaluation and 250 at the second (95% CI). MEASUREMENTS: Two internal
      audit, retrospective evaluations were made, by means of review of clinical
      records by health professionals at the centre (peer review). The variables
      reviewed were activities of PPAHP for adults. RESULTS: The overall improvement
      attained was 64.45% (Pareto Diagram). All PPAHP activities (except Anamnesis for
      Metrorrhagia) showed significant improvement in compliance (P < .05). The PPAHP
      activity with the highest degree of improvement was Mammography, which went up
      from 3.70% (+/-7.12) of compliance (first evaluation) to 83.87% (+/-12.95)
      (second evaluation). CONCLUSIONS: Degree of compliance with PPAHP improved with
      time, except for anamnesis on metrorrhagia. The activity with the greatest degree
      of improvement was mammography.

PMID- 17020714
TI  - [Ethical problems in prescribing drugs of not very significant clinical
      effectiveness].

PMID- 17020715
TI  - [Doctor-induced demand: Applications of economic theory in clinical practice].

PMID- 17020716
TI  - [EVAN-50 study: Effectiveness of polysaccharide pneumococcus vaccine in
      preventing pneumococcal infections in the over-50 population].
AB  - OBJECTIVE: To assess the effectiveness of 23-valent polysaccharide vaccine in
      preventing severe pneumococcal infections in adults over 50 years old. DESIGN:
      Case-control study. SETTING: Primary Health Care Service, Tarragona, Spain.
      PATIENTS: A total of 270 patients >50 with severe pneumococcal disease (invasive
      pneumococcal disease and non-bacteraemic pneumococcal pneumonia) and 540 control
      patients randomized from the primary care Centres of the case patients. Case and
      control patients will be matched for age, sex, family physician, and level of
      risk for pneumonia. MAIN MEASUREMENTS: Odds ratio (OR) will be used to measure
      the vaccine effect. Multivariate logistical regression, adjusted for age, sex,
      and comorbidity, will be conducted. Vaccine effectiveness (VE) will be calculated
      by the formula, VE = 1-OR. Vaccine effectiveness will be distinguished for the
      various age groups and at each risk stratum. It will also be estimated by means
      of indirect cohort analysis, taking as cases the infection caused by vaccine
      serotypes and as controls infection caused by non-vaccine serotype. DISCUSSION:
      The study will give an answer in terms of effectiveness of the vaccine for
      several age and risk strata. It will contribute to taking a decision regarding
      the controversial question of the systematic indication, or otherwise, of this
      vaccine for the elderly.

PMID- 17020717
TI  - [Reduction in the prescription of antibiotics in pharyngoamygdalitis and
      sinusitis by means of an audit].

PMID- 17020718
TI  - [Managing cardiac failure in a peri-urban health centre: Adherence to treatment
      guidelines].

PMID- 17020719
TI  - [Active recruitment of young people with diagnosed hypertension who do not attend
      clinics. High cardiovascular profitability?].

PMID- 17020720
TI  - [Qualitative indicators in antibiotic prescription: Are they the most appropriate
      ones?].

PMID- 17020721
TI  - [Spaniards do not follow the mediterranean diet].

PMID- 17020722
TI  - [Breast cancer screening].

PMID- 17020723
TI  - [Sleep-related respiratory disorders in childhood].

PMID- 17020724
TI  - [Video-polysomnography in preterm infants with birth weight under 1,800 g].
AB  - INTRODUCTION: Neonatal video-polysomnography (VPSG) in preterm infants is
      indicated to rule out sleep-related respiratory disturbances before discharge
      from neonatal units and to study neonatal sleep patterns and associated
      pathologic conditions. OBJECTIVE: To study the presence of apnea, hypopnea, and
      periodic breathing in preterm infants with low birth weight (< 1,800 g) and to
      describe their cardio-respiratory variability, electroencephalogram (EEG)
      abnormalities, and brain maturity in connection with sleep stages. METHOD: We
      performed a cross-sectional, descriptive study through review of the clinical
      histories of preterm infants with a birth weight < 1,800 g who had undergone VPSG
      (2001-2003). The most common indication for VPSG was the presence of sleep apneas
      and oxygen desaturation. The data obtained were used for descriptive statistical
      analysis. RESULTS: Thirty-one infants were studied, with a mean gestational age
      of 27.8 weeks and a mean birth weight of 1,158 g. The most frequently associated
      condition was hyalin membrane disease (68 %). Cardiorespiratory impairment was
      detected in 65 %, altered sleep pattern in 6 %, immature EEG recording in 32 %,
      abnormal pattern in 13 %, and immature plus abnormal pattern in 3 %. Sixty-nine
      percent of the infants required home monitoring and 23 % needed oxygen at home.
      Four infants were readmitted on several occasions due to apnea. CONCLUSION: We
      wish to stress the importance of carrying out VPSG with suitable methodology in
      preterm infants with cardiorespiratory or neurological impairment in order to
      detect abnormalities on EEG and to assess brain maturity and sleep-related
      abnormal respiratory events.

PMID- 17020725
TI  - [Diagnostic utility of nocturnal in-home respiratory polygraphy].
AB  - INTRODUCTION: Sleep apnea-hypopnea syndrome (SAHS) is relatively frequent in
      children. The gold standard for diagnosis is polysomnography. However, because of
      technical difficulties and the cost of this method, new alternatives have become
      available, such as respiratory polygraphy (RP) performed at home or in hospital,
      which have provided satisfactory results in children with clinical suspicion of
      SAHS. OBJECTIVE: The aim of this study was to analyze the diagnostic utility of
      in-home RP in the diagnosis of SAHS in a sample of boys and girls referred to the
      pediatric respiratory care department for suspected sleep apnea, snoring, or
      both. MATERIAL AND METHODS: In all patients, a history and physical examination
      were performed; X-ray of the chest and cavum and RP were carried out. The
      following qualitative variables were analyzed: place where RP was performed, the
      result, sex, the reason for consulting, place of residence, results of
      otorhinolaryngological examination, and treatment. The quantitative variables
      analyzed were age, total number of apneas, total number of hypopneas, apnea
      index/hour, hypopnea index/hour, mean and minimum SpxO2, number of snores per
      hour and the snore index/hour. Statistical analysis was performed using Pearson's
      chi-square test and Student's t-test. RESULTS: A total of 132 patients were
      studied, 44 (33.3 %) through in-home RP (group 1) and 88 (66.6 %) through in
      hospital RP (group 2). In group 1, two recordings (4.5 %) were considered
      nonvalid. The mean age of the patients was 8.3 years (SD 3.02). The results
      [means (standard deviation)] of in-home RP were as follows: apnea-hypopnea index
      (AHI)/h: 3.4 (4.3); mean SpxO2: 97.3 (1.8); minimum SpxO2: 87.7 (10.3). In group
      2, four recordings (4.5 %) were nonvalid. The mean age of the patients was 7.4
      years (SD 3). The results of in-hospital RP were as follows: AHI/h: 4.45 (5.4);
      mean SpxO2: 96.8 (1.8); minimum SpxO2: 87 (11). No significant differences were
      found between the validity of in-home and in-hospital RP. Likewise, no
      significant differences were found between AHI/h, SpxO2 and in-home and in
      hospital RP. CONCLUSION: In conclusion, in our sample, the diagnostic utility of
      in-home RP was equal to that of in-hospital RP. In-home RP allows the possibility
      of performing a more physiological sleep study and, by eliminating the cost of
      hospitalization, is more cost-efficient. Therefore, in-home RP is a valid and
      reliable technique for the diagnosis of childhood SAHS.

PMID- 17020726
TI  - [The efficiency (cost-effectiveness) of palivizumab as prophylaxis against
      respiratory syncytial virus infection in premature infants with a gestational age
      of 32-35 weeks in Spain].
AB  - OBJECTIVES: To evaluate the efficiency (cost-effectiveness) of palivizumab in
      preventing severe respiratory syncytial virus (RSV) infection in premature
      infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk
      factors (RF) in Spain. METHODS:  DESIGN: decision tree model using data from the
      scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants
      with GA 32-35 and two or more RF who received palivizumab) sponsored by the
      Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life
      years (QALY) gained. PERSPECTIVES: the national health service (NHS), which
      includes direct costs (administration of palivizumab and hospital admissions),
      and the societal perspective, which also includes indirect costs (the child's
      future lost productivity). Discount: 3 % annually for effectiveness and indirect
      costs. Sensitivity analysis: construction of 37 scenarios modifying variables
      related to effectiveness and costs. RESULTS: Prophylaxis with palivizumab in
      premature infants with GA 32-35 and two or more RF produced an incremental cost
      effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an
      ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity
      analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most
      favorable scenario) to 23,276 euro/QALY (least favorable scenario). CONCLUSIONS:
      Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants
      with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective,
      since the cost of a QALY, even in the least favorable scenarios, is lower than
      the threshold of 30,000 Euro/QALY considered socially acceptable in Spain.

PMID- 17020727
TI  - [Incidence and cost of hospitalizations for bronchiolitis and respiratory
      syncytial virus infections in the autonomous community of Valencia in Spain (2001
      and 2002)].
AB  - OBJECTIVE: To assess the incidence and costs of hospitalizations for
      bronchiolitis and respiratory syncytial virus (RSV) infections the Autonomous
      Community of Valencia, Spain. METHODS: The minimum data set (MDS) of the
      Autonomous Community of Valencia was analyzed. Hospital discharges with the codes
      for bronchiolitis (with or without etiologic determination) and RSV infections
      occurring in 2001 and 2002 in children less than 2 years old were included.
      Second cases of bronchiolitis and RSV infections of possible nosocomial origin
      occurring during prolonged hospitalization were excluded. The average cost of
      hospitalization in a pediatric ward was estimated at euro 310.30 per day. To
      calculate the incidence, we assumed that 95 % of the hospitals reported to the
      MDS; the population used was that of the National Census, 2001. RESULTS: A total
      of 3,705 hospitalizations were obtained, of which 3,507 were coded as
      bronchiolitis and 42.2 % of these were RSV-positive. Virological assessment
      varied greatly among hospitals. Hospitalizations were most frequent between
      October and April, with no differences between the two years. The incidence of
      bronchiolitis hospitalization was 40.2 cases/1000 children < 1 year/year, with an
      average annual cost of 3,618 thousand Euros. CONCLUSIONS: The cost of
      bronchiolitis hospitalizations is high. Microbiological investigation is low in
      some hospitals, leading the economic impact of RSV on society to be
      underestimated.

PMID- 17020728
TI  - [Influenza vaccination in patients admitted to a tertiary hospital. Factors
      associated with coverage].
AB  - INTRODUCTION: Children aged less than 2 years old and those with chronic diseases
      have a high risk of complications and hospitalization due to influenza. Despite
      the broad consensus in the literature on the indication for annual immunization
      of these patients, less than 30 % of the children with high-risk underlying
      conditions are immunized each year. The aim of this study is to determine the
      influenza vaccine coverage in children with high-risk underlying conditions
      admitted to a university hospital. PATIENTS AND METHODS: We performed a cross
      sectional study of patients aged from 6 months to 18 years old with high-risk
      medical conditions and who had been hospitalized between January and May, 2005 in
      the Vall d'Hebron University Hospital (Barcelona). Influenza vaccine coverage,
      factors associated with immunization, and the reasons for nonvaccination were
      analyzed. RESULTS: Overall vaccine coverage was 23.5 %. The highest vaccination
      coverage was found in patients with congenital heart disease, chronic respiratory
      disease, and asthma (43.2 %, 42.9 % and 28.6 %, respectively). The factors most
      frequently associated with influenza vaccination were the type of underlying
      disease, having been immunized against influenza in the previous season, having
      received the pneumococcal vaccine, and age younger than 5 years. The main reason
      for nonvaccination was the lack of influenza vaccine recommendation by health
      professionals (95.3 %). CONCLUSIONS: Influenza vaccine coverage in children with
      high-risk conditions is low. Strategies to increase awareness among health
      professionals on the importance of recommending influenza immunization are
      required.

PMID- 17020729
TI  - [Prevalence of dental caries: comparison between immigrant and autochthonous
      children].
AB  - INTRODUCTION: Immigration to Spain has been high in recent years, especially in
      some autonomous communities. In both deciduous and permanent teeth, immigrant
      children have a higher number of dental caries and a lower number of restored
      teeth than autochthonous schoolchildren. Few studies have compared the prevalence
      of dental caries between immigrant and autochthonous children. OBJECTIVE: To
      determine the prevalence of dental caries in two groups of children: an immigrant
      group and an autochthonous group. MATERIAL AND METHOD: The study sample consisted
      of 600 children (235 immigrant children and 365 autochthonous children) aged
      between 6 and 10 years old who were living in the autonomous community of
      Valencia. The children were examined by two specialists, an odontologist and a
      pediatrician. RESULTS: The prevalence of dental caries was higher in immigrant
      children than in autochthonous children. In deciduous dentition, the prevalence
      of caries was 47.23 % and 32.05 % in immigrants and autochthonous children,
      respectively. In permanent dentition, the prevalence was 53.19 % and 35.34 %,
      respectively. CONCLUSIONS: The prevalence of dental caries was higher in
      immigrant children than in autochthonous children. Pediatricians and/or
      odontologists should aim to improve knowledge of good dental health care and
      habits among immigrant children and their parents.

PMID- 17020730
TI  - [Guidelines for the diagnosis and management of sleep apnea-hypoapnea syndrome in
      children].

PMID- 17020731
TI  - [Scrotal edema: a rare complication of percutaneous central venous atheters].
AB  - The use of percutaneous central venous catheters in neonatal intensive care units
      is becoming increasingly common. Numerous studies support the safety and
      effectiveness of the use of these catheters for the infusion of parenteral
      nutrition or medication. We describe a male patient with a gestational age of 32
      weeks who showed swelling of the external genitals during the fifth day of life.
      The etiology was initially thought to be infectious. A review of X-rays revealed
      the introduction of the silastic catheter to the spermatic vessels. When the
      catheter was withdrawn, the genital swelling disappeared in a few hours. The most
      frequently described complications associated with percutaneous central venous
      catheters are infectious. Other complications that have been described are
      thrombosis, embolism, and perforation of the catheter with leakage of fluid to
      the extravascular space. The case described herein is an unusual complication
      that has not been previously described and resulted from poor positioning of the
      catheter tip. Diagnostic delay can cause serious complications.

PMID- 17020732
TI  - [Aortic and cerebral trombosis caused by hypernatremic dehydration in an
      exclusively breast-fed infant].
AB  - Complete aortic thrombosis is rare in neonates. Because it carries high morbidity
      and mortality, this entity requires aggressive and early treatment. This report
      describes an 8-day-old healthy and exclusively breast-fed infant, without
      specific coagulopathy, who developed complete aortic and cerebral venous
      thrombosis, which was attributed to inadequate breast-feeding and severe
      hypernatremic dehydration. Early systemic anticoagulation and thrombolytic
      therapy allowed complete resolution of the problem.

PMID- 17020733
TI  - [Long-gap esophageal atresia: effect of the timing of extubation on outcome].

PMID- 17020734
TI  - [Bilateral palpebral coloboma: an infrequent ocular malformation].

PMID- 17020735
TI  - [Rickettsia slovaca infection alter a tick bite].

PMID- 17020736
TI  - [Complicated gingivoestomatitis].

PMID- 17020737
TI  - [Subcutaneous nodulus as the form of onset of hemophilia A in an infant].

PMID- 17020738
TI  - [Beckwith-Wiedemann syndrome and epilepsy].

PMID- 17020739
TI  - [Cutaneous hyperpigmentation of the distal phalanges in a newborn infant].

PMID- 17020740
TI  - [Pustular lymphomatoid papulosis].

PMID- 17020741
TI  - [Leukocyturia with negative urine culture].

PMID- 17020742
TI  - [Descriptive study of vascular complications secondary to antithrombotic agents
      and percutaneous cardiovascular interventionism in a coronary unit].
AB  - Administration of drugs in the patients diagnosed of acute coronary syndrome and
      treated with percutaneous transluminal coronary angioplasty (PTCA) has noticeably
      reduced morbidity-mortality and appearance of new ischemic events. However, these
      drug agents may cause bleeding problems secondary to therapeutic intervention.
      The objectives of this research are: to know the incidence of vascular
      complications developed in patients treated with antithrombotic drugs and
      percutaneous cardiovascular interventionism and describe variables that may be
      related with their appearance. A retrospective descriptive study was done on the
      registries of the clinical histories of 153 patients subjected to primary
      angioplasty and rescue treatment during the period ranging from October 1, 2001
      to October 31, 2002 in the Hospital Universitario Marques de Valdecilla. Mean age
      of the patients was 63 years, 75% diagnosed of acute myocardial infarction and
      71% subjected to primary angioplasty. Drugs used were anticoagulants,
      antiaggregants and fibrinolytics. Furthermore compression methods and arterial
      sheath duration time were analyzed. Complications appeared in 39% of the
      patients, the most frequent complication being the hematoma in 28%. It is
      concluded that when antithrombotic drugs are combined with PTCA, vascular
      complications appear in one third of the patients studied, the appearance of
      hematomas standing out in the first place and in the second place, femoral
      bleeding. The main study variables also contributing to their appearance are the
      permanence of the sheath and its removal.

PMID- 17020743
TI  - [Care plan versus care protocol. Comparative analysis in patients subjected to
      cardiac catheterism].
AB  - The nursing product marks the present and future of the nursing staff. The tools
      used in the nursing staff should be complete and favor their work. The importance
      of the cares, during the stay of the patients in the intensive care units, is
      justified by the obtaining of results and some levels of quality that are
      adequate for the health care setting. The project aims to know the efficacy of
      the registered nursing care procedure, care plan or care protocol in an intensive
      care unit, with a system of computerized clinical records. The resulting
      information shows a value for the time dedicated to work with the plan greater
      than that used with the protocol (p = 0.01). In turn, the quality indicators used
      in both systems are graded as acceptable, although they obtain better results in
      the care plan. The nursing staff that participate in the study consider that the
      utility of the care plan in the unit is limited or null for 42.9% and 21.4%,
      respectively. It should be remembered that the work system in forced in the unit
      for the nursing care is a care protocol In conclusion, we state that the care
      plan has better quality in the records than the care protocol, while it requires
      greater time to fill out the nursing records.

PMID- 17020744
TI  - [ Contact isolation and prevention of spreading of serious infections in an
      intensive care unit. Description of a protocol].
AB  - Hospital infection (HI) represents a serious care problem in critical patients.
      The presence of this complication is associated to an increase in the baseline
      seriousness of the patient, that is translated into greater care effort,
      multiplication of workload and greater mortality. This situation is clearly
      complicated when the causal agent of the infection is a multiresistant bacteria,
      since it also requires specific measures aimed at avoiding crossed transmission
      of the infection to other patients in addition to route treatment. The objective
      of the Nursing Note is to communicate our routine action in the face of this
      problem. From January 2003 to December 2004, 2420 patients were admitted to our
      Department. Of these 190 had some ICU hospital acquired infection (8.48%).
      Isolation steps were begun in 112 patients (4.62%) and also preventive measures
      as they were immunodepressed patients (inverse isolation) or patients at risk of
      presenting colonization or infection by multiresistant germs (preventive
      isolation) or due to suffering a demonstrated infection by said microorganisms.
      The mean seriousness, measured by the Simplified Acute Physiology Score (SAPS
      II), of the sample was 30+/-16 points. Those infected had a mean seriousness of
      44+/-15 points and those isolated 49+/-19 points. Nursing workloads, measured by
      Nine Equivalents of Nursing Manpower Use Score (NEMST) were 150+/-274 points for
      all the sample, while the infected patients had 737+/-460 and the isolated ones
      811+/-452 points. Global mortality in said period was 12.6%, while those infected
      had a mortality of 32% and the isolated ones 43%. The average costs per stay were
      5069 euro. Patients who suffered any infection during their stay in the ICU
      increased their stay cost up to 26,630 euro and those isolated up to 29,050 euro.
      Faced with this situation, it was decided to stress the Contact Isolation
      procedures to achieve correct fulfillment of the preventive measures and achieve
      reduction in the hospital infection rates and crossed transmission between
      patients by multiresistant pathogens.

PMID- 17020745
TI  - Functions of carotenoids in xanthorhodopsin and archaerhodopsin, from action
      spectra of photoinhibition of cell respiration.
AB  - The recent discovery of a carotenoid light-harvesting antenna in xanthorhodopsin,
      a retinal-based proton pump in Salinibacter ruber, made use of photoinhibition of
      respiration in whole cells to obtain action spectra [Balashov et al. Science 309,
      (2005) 2061-2064]. Here we provide further details of this phenomenon, and
      compare action spectra in three different systems where carotenoids have
      different functions or efficiencies of light-harvesting. The kinetics of light
      induced inhibition of respiration in Salinibacter ruber was determined with
      single short flashes, and the photochemical cross section of the photoreaction
      was estimated. These measurements confirm that the xanthorhodopsin complex
      includes no more than a few, and most likely only one, carotenoid molecule, which
      is far less than the core complex antenna of photosynthetic bacteria. Although
      the total cross-section of light absorption in the purple bacterium
      Rhodospirillum rubrum greatly exceeds that in Salinibacter, the cross-sections
      are roughly equivalent in the shared wavelength range. We show further that
      despite interaction of bacterioruberin with archaerhodopsin, another retinal
      based proton pump, there is no significant energy transfer from this carotenoid.
      This emphasizes the uniqueness of the salinixanthin-retinal interaction in
      xanthorhodopsin, and indicates that bacterioruberin in Halorubrum species has a
      structural or photoprotective rather than energetic role.

PMID- 17020746
TI  - Redox potentials of the blue copper sites of bilirubin oxidases.
AB  - The redox potentials of the multicopper redox enzyme bilirubin oxidase (BOD) from
      two organisms were determined by mediated and direct spectroelectrochemistry. The
      potential of the T1 site of BOD from the fungus Myrothecium verrucaria was close
      to 670 mV, whereas that from Trachyderma tsunodae was >650 mV vs. NHE. For the
      first time, direct electron transfer was observed between gold electrodes and
      BODs. The redox potentials of the T2 sites of both BODs were near 390 mV vs. NHE,
      consistent with previous finding for laccase and suggesting that the redox
      potentials of the T2 copper sites of most blue multicopper oxidases are similar,
      about 400 mV.

PMID- 17020747
TI  - Fronto-hippocampal function during temporal context monitoring in schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have difficulty using contextual
      information to recall the source of information. Given the importance of the
      hippocampus and prefrontal cortex (PFC) in this type of memory, we hypothesized
      that this cognitive deficit stemmed from aberrant fronto-hippocampal activation
      during memory retrieval. METHODS: Patients with schizophrenia (n = 16) and age
      matched comparison subjects (n = 16) underwent functional magnetic resonance
      imaging while performing a verbal memory task that requires intact use of
      temporal context. Blood oxygen-level dependent (BOLD) signal during correct
      memory decisions was compared between the two groups with statistical parametric
      mapping. RESULTS: Contrary to our hypotheses, patients with schizophrenia
      demonstrated nearly identical memory performance to that of the comparison
      subjects. Despite this, there were significant between-group BOLD signal
      differences, including a pattern of task-dependent hypofrontality or
      hyperfrontality. In addition, whereas the highest-performing subset of the
      comparison group demonstrated robust modulation of hippocampal activity, this
      pattern was not seen in the highest-performing patients with schizophrenia.
      CONCLUSIONS: Despite memory performance similar to that of comparison subjects,
      patients with schizophrenia activated different neural pathways to achieve this
      success. This might reflect underlying neuropathology in fronto-hippocampal
      circuitry, the use of an alternate cognitive strategy to accomplish task
      performance, or both.

PMID- 17020748
TI  - MAP kinase additively activates the mouse Per1 gene promoter with CaM kinase II.
AB  - In a previous study, we showed that the Ca2+/calmodulin-dependent protein kinase
      IIdelta (CaMKIIdelta) activates the mouse Per1 (mPer1) promoter through a 5'
      GAGGGG-3' motif near exon1B. Here we use luciferase reporter gene assays to
      document additive activation of the mPer1 promoter by CaMKIIdelta and mitogen
      activated protein kinase (MAPK) pathways. Transfection of constitutively active
      MEKK markedly increased mPer1 promoter activity in NB2A cells. Experiments using
      MAPK inhibitors and dominant-negative c-Jun NH2-terminal kinase 1 (JNK1) showed
      that extracellular signal-regulated kinase (ERK) accounts for MEKK-induced mPer1
      gene activation. We next defined the ERK-responsive region in the mPer1 promoter.
      A region from -1735 to -1721 was required for ERK-induced promoter activation. We
      also identified a CaMKII-responsive element near exon 1B. Although mutation of
      the CaMKII-responsive element has no effect on the ERK responsiveness,
      elimination of a GC-rich sequence downstream of the CaMKII-responsive region
      totally abolished ERK responsiveness. Finally, ERK-induced promoter activation
      was additively potentiated by co-transfection with active CaMKIIdelta. These
      results suggest that additive activation by ERK and CaMKII, most likely as a
      result of photic stimulation in the suprachiasmatic nucleus, plays a critical
      role in activating the mPer1 gene promoter.

PMID- 17020749
TI  - A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C
      protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has shown robust
      neuroprotective and neuroreparative activities in various animal models of
      Parkinson's Disease or amyotrophic lateral sclerosis (ALS). The successful use of
      GDNF as a therapeutic in humans, however, appears to have been hindered by its
      poor bioavailability to target neurons in the central nervous system (CNS). To
      improve delivery of exogenous GDNF protein to CNS motor neurons, we employed
      chemical conjugation techniques to link recombinant human GDNF to the neuronal
      binding fragment of tetanus toxin (tetanus toxin fragment C, or TTC). The
      predominant species present in the purified conjugate sample, GDNF:TTC, had a
      molecular weight of approximately 80 kDa as determined by non-reducing SDS-PAGE.
      Like GDNF, addition of GDNF:TTC to culture media of neuroblastoma cells
      expressing GFRalpha-1/c-RET produced a dose-dependent increase in cellular
      phospho-c-RET levels. Treatment of cultured midbrain dopaminergic neurons with
      either GDNF or the conjugate similarly promoted both DA neuron survival and
      neurite outgrowth. However, in contrast to mice treated with GDNF by
      intramuscular injection, mice receiving GDNF:TTC revealed intense GDNF
      immunostaining associated with spinal cord motor neurons in fixed tissue
      sections. That GDNF:TTC provided neuroprotection of axotomized motor neurons in
      neonatal rats further revealed that the conjugate retained its GDNF activity in
      vivo. These results indicate that TTC can serve as a non-viral vehicle to
      substantially improve the delivery of functionally active growth factors to motor
      neurons in the mammalian CNS.

PMID- 17020750
TI  - The growth compromised HSV-2 mutant DeltaRR prevents kainic acid-induced
      apoptosis and loss of function in organotypic hippocampal cultures.
AB  - We have previously shown that the HSV-2 anti-apoptotic protein ICP10PK is
      delivered by the replication incompetent virus mutant DeltaRR and prevents kainic
      acid (KA)-induced epileptiform seizures and neuronal cell loss in the mouse and
      rat models of temporal lobe epilepsy. The present studies used DeltaRR and the
      ICP10PK deleted virus mutant DeltaPK to examine the mechanism of neuroprotection.
      DeltaRR-infected neuronal cells expressed a chimeric protein in which ICP10PK is
      fused in frame to LacZ (p175) while retaining ICP10PK kinase activity. DeltaPK
      infected neuronal cells expressed a mutant ICP10 protein that is deleted in the
      PK domain and is kinase negative (p95). p175 and p95 were expressed in CA3 (86+/
      3%) and CA1 (69+/-7%) cells from DeltaRR or DeltaPK-infected organotypic
      hippocampal cultures (OHC) and 80-85% of the ICP10 positive cells co-stained with
      antibody to beta(III) Tubulin (neuronal marker). DeltaRR, but not DeltaPK,
      inhibited KA-induced cell death and caspase-3 activation in CA3 neurons, an
      inhibition seen whether DeltaRR was delivered 2 days before or 2 days after KA
      administration (95% neuroprotection). Neuroprotection was associated with ERK and
      Akt activation and was abrogated by simultaneous treatment with the MEK (U0126)
      and PI3-K (LY294002) inhibitors. DeltaRR-mediated neuroprotection was associated
      with increased expression of the anti-apoptotic protein Bag-1 and decreased
      expression of the pro-apoptotic protein Bad. The surviving neurons retained
      normal synaptic function potentially related to increased expression of the
      transcription factor CREB. The data indicate that DeltaRR is a promising platform
      for neuroprotection from excitotoxic injury.

PMID- 17020751
TI  - Cortical correlates of illusory hand movement perception in humans: a MEG study.
AB  - The present study aimed to investigate cortical activity associated with
      perception of illusory hand movements elicited by tendon vibration using
      magnetoencephalography (MEG) in humans. We compared MEG responses in two
      conditions of stimulation, "illusion" and "no illusion". In the "illusion"
      condition, covibration at different frequencies applied on the tendons of the
      right wrist flexor and extensor muscle groups evoked illusory movements of the
      hand. In the "no illusion" condition, covibration was delivered at the same
      frequency on both tendon groups and no movement was perceived. In both
      experimental conditions, equivalent current dipoles (ECD) were identified in each
      of four time windows: 0-200 ms, 200-400 ms, 400-600 ms and 600-800 ms. Our data
      showed similar activation in S1, superior parietal gyrus and supramarginal gyrus
      in both conditions, whereas the supplementary motor area, M1 and the left angular
      gyrus were found active in the "illusion" condition only. Our results confirmed
      the role of posterior parietal areas as well as motor areas in the arising of
      kinesthetic sensations. The hypothesis of an interaction between the angular
      gyrus and the primary motor area occurring about 400 ms after the beginning of
      the stimulation is discussed.

PMID- 17020752
TI  - The role of leptin in the development of the cortical neuron in mouse embryos.
AB  - Leptin is an obese gene product that decreases appetite and raises energy
      expenditure in adults. We previously reported that leptin was detected in the
      sera of mouse embryos and leptin receptors were expressed in the mouse embryonic
      cerebrum, suggesting that leptin plays a role in cerebral development. In this
      study, we injected leptin into the lateral ventricle of the cerebrum in leptin
      deficient ob/ob mouse embryos to investigate the function of leptin in cerebral
      development. When leptin was injected on embryonic day (E) 14, the ratio of the
      number of cells in the cortical plate (CP) to that in the intermediate zone (IZ)
      was higher in leptin-injected than in vehicle-injected ob/ob embryos on E16,
      although there was no significant difference in the number of cells in the
      ventricular zone (VZ), IZ, or CP between these groups. The number of postmitotic
      BrdU-positive CP cells was larger in leptin-injected than in vehicle-injected
      ob/ob embryos on E16 and E17 when BrdU labeling and leptin injection were
      performed on E14. By in situ hybridization, NPY mRNA expression in CP neurons on
      E18 was weaker in leptin-injected than in vehicle-injected ob/ob embryos when
      leptin was injected on E16. These results suggest that leptin promotes the
      migration of neuronal lineage cells to CP and that the leptin-NPY axis in neurons
      works in the cerebral cortex on E16.

PMID- 17020753
TI  - Molecular targets of tea polyphenols in the cardiovascular system.
AB  - Tea-derived polyphenols have attracted considerable attention in the prevention
      of cancer and cardiovascular diseases. In comparison to tumour cells, the
      elucidation of their molecular targets in cardiovascular relevant cells is still
      at the beginning. Although promising experimental and clinical data demonstrate
      protective effects for the cardiovascular system, little information is actually
      available on how these beneficial effects of tea polyphenols are mediated at the
      cellular level. By affecting the activity of receptor and signal transduction
      kinases, both catechins and theaflavins--the major ingredients of green and black
      tea, respectively--exert a variety of cardiovascular beneficial effects. In
      general, the number and positions of galloyl groups have major influence on the
      potency of polyphenols. Compared to their broad impact on cellular signal
      transduction, tea polyphenols reveal little transcriptional effects. However,
      more detailed and profound analysis of molecular actions in different cells of
      the cardiovascular system is necessary before safe clinical use of tea
      polyphenols for treatment of cardiovascular diseases will become possible.

PMID- 17020754
TI  - Arsenic trioxide eluting stent reduces neointima formation in a rabbit iliac
      artery injury model.
AB  - OBJECTIVE: In-stent restenosis is caused by the neointimal hyperplasia, which
      involves abnormal growth of vascular smooth muscle cells (VSMC). Arsenic trioxide
      (As2O3) is known to be a potent inhibitor of cell proliferation. We therefore
      studied the role of an As2O3 eluting stent in the prevention of restenosis in a
      rabbit iliac artery model. METHODS AND RESULTS: Bare stents, or stents coated
      with poly-L-lactic acid (PLLA) and either 40 microg of As2O3, 180 microg of
      paclitaxel or vehicle were implanted into the left proximal iliac arteries of New
      Zealand rabbits. The delivery of drugs from stents in vitro and in vivo was
      evaluated by atomic fluorescence spectrophotometry and high-performance liquid
      chromatography, respectively. Histomorphometric measurements at 7 or 28 days
      showed that, comparing to rabbits receiving the PLLA stent, in animals treated
      with As2O3 eluting or paclitaxel eluting stent neointima thickness was reduced by
      50% and 46%, the absolute neointimal area was reduced by 53% and 44%, while the
      absolute luminal area was increased by 46% and 43%, respectively. There were no
      significant differences in injury or inflammation scores among PLLA, As2O3
      eluting and paclitaxel eluting stents. As2O3 eluting stent induced more TUNEL
      positiv VSMC than the other stents. As2O3 levels measured in the arterial tissue
      were much higher than those in serum, which were nearly undetectable at 7 days
      after stent implantation. In in vitro studies, cultured rabbit arterial VSMC were
      stimulated with As2O3 or paclitaxel and analyzed for their cell cycle progression
      and apoptosis by flow cytometry and electron microscopy. As2O3 treatment resulted
      in a reduction of VSMC number in G1 phase with a concomitant increase in
      apoptosis of VSMC, whereas paclitaxel treatment led to blocking of VSMC in the
      G2/M phase. CONCLUSION: In a rabbit iliac artery model PLLA coated As2O3 eluting
      stent significantly suppressed in-stent restenosis by reducing proliferation and
      inducing apoptosis of VSMC.

PMID- 17020755
TI  - Variation of interleukin 8 -251 A>T polymorphism in worldwide populations and
      intra-ethnic differences in Japanese populations.
AB  - BACKGROUND: Interleukin-8 (IL8) is a member of the family of chemokines. The IL8
      gene has polymorphic variations, and the genotype of IL8 -251 A>T is associated
      with smoking behavior and cancer progression. METHOD: IL8 -251 A>T polymorphism
      were investigated in Japanese, from 5 different areas, in Ovambo, Turkish,
      Mongolian and Korean populations by PCR with confronting 2-pair primers (PCR
      CTPP) analysis. RESULTS: A subpopulation analysis of Japan revealed a north-to
      south increase in the frequency of the IL8 -251 T allele. Among the 5 groups, the
      Japanese showed the highest frequency of mutant allele followed by the Turks. The
      distribution pattern in the Japanese was different from those of Mongolians and
      Koreans. In the Ovambo population, no mutant allele homozygote subject was found
      and the frequency of mutant alleles was the lowest, similar to that in Gambians.
      CONCLUSION: The present study is the first to demonstrate the Japan population
      inter-prefecture differences in IL8 -251 A>T polymorphism as well as a certain
      genetic heterogeneity in the worldwide distribution of IL8 -251 A>T polymorphism.
      The distribution results may help define the true significance of IL8 -251 A>T
      polymorphism as a marker for smoking behavior in populations worldwide.

PMID- 17020756
TI  - Asymmetric dimethylarginine (ADMA) and hyperhomocysteinemia in patients with
      acute myocardial infarction.
AB  - OBJECTIVES: We sought to investigate the association between increased levels of
      asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase
      inhibitor, and total plasma homocysteinemia (tHcy) in patients with acute
      myocardial infarction (AMI). DESIGN AND METHODS: In 138 patients hospitalized for
      AMI <24 h on admission, serum levels of ADMA, its symmetric stereoisomer (SDMA)
      and tHcy were measured. RESULTS: ADMA was positively associated with SDMA
      (p<0.001) and tHcy (p=0.03) but not with estimated glomerular filtration rates
      (eGFR, p=0.96), while tHcy strongly correlated with eGFR (p=0.002) and SDMA
      (p<0.001). By multiple linear regression, SDMA but not ADMA was independently
      associated with tHcy (p=0.005). CONCLUSION: Our findings suggest that, in AMI
      patients, hyperhomocysteinemia is indirectly related to ADMA levels via renal
      function. Moreover, ADMA level was independent of traditional cardiovascular risk
      factors in AMI patients. Interestingly, our findings suggest that SDMA could be a
      good risk indicator for cardiovascular disease in AMI patients.

PMID- 17020757
TI  - Hyperhomocysteinemia is associated with deep venous thrombosis of the lower
      extremities in Tunisian patients.
AB  - OBJECTIVES: To test the association between hyperhomocysteinemia (HHC) and deep
      venous thrombosis (DVT) of lower extremities in Tunisians. DESIGN AND METHODS:
      This case-control study included 90 patients with DVT of the lower extremities
      and 160 healthy controls. Plasma homocysteine, vitamin B(12) and folate were
      determined using immunoenzymatic methods. Logistic regression models were
      performed to test whether the association between HHC and DVT is independent and
      to precise determinants of HHC in DVT patients. RESULTS: Plasma total
      homocysteine concentrations were significantly higher in patients with DVT
      (17.4+/-11.5 micromol/L) and in patients with idiopathic DVT (15.2+/-6.4
      micromol/L) as compared to controls (11.5+/-3.3 micromol/L). HHC was
      significantly associated (p<0.001) with all DVT (OR, 8.82; 95% CI, 3.96-19.6) as
      well as idiopathic DVT (OR, 7.40; 95% CI, 3.01-10.8). These associations
      persisted after adjustment for several thrombosis risk factors. In patients with
      DVT, HHC was related to folate and vitamin B(12) concentrations, but neither to
      the type of occurrence nor to the recurrence of DVT. CONCLUSION: HHC is
      independently associated with first DVT of lower extremities in Tunisians.
      Homocysteine should be assessed in patients with DVT and the effect of vitamin B
      supplementation should be tested among them.

PMID- 17020758
TI  - The Pax2/5/8 gene egl-38 coordinates organogenesis of the C. elegans egg-laying
      system.
AB  - Organogenesis requires coordinated development between different tissues and
      cells. The Pax family of transcription factors coordinates multiple developmental
      events in organs including the kidney, thyroid and the eye. Studying Pax factors
      in different organisms should identify unifying characteristics of organ
      development with implications to both development and disease. Here we
      investigate the function of the Pax2/5/8 transcription factor EGL-38 in
      coordinating development of the C. elegans egg-laying system. A functional egg
      laying system requires cell fate specification events in the epithelial cells of
      the vulva as well as the mesodermal cells in the uterus of the somatic gonad.
      Using gene expression studies, genetic mutant analysis and genetic mosaics, we
      show that egl-38 has functions in both tissues of the organ to promote its
      development. We incorporate these results together with previous results to
      propose that EGL-38 plays multiple roles in the development of the egg-laying
      system, acting to both promote cell fate and to coordinate the development
      between different cell types. As the Pax2 gene performs similar roles in the
      development of the mammalian kidney, we show that coordinating organogenesis is a
      conserved function for Pax2/5/8 transcription factors.

PMID- 17020759
TI  - Oxidized ATP decreases beta-actin expression and intracellular superoxide
      concentrations in RBA-2 type-2 astrocytes independently of P2X7 receptor.
AB  - Periodate-oxidized 2',3'-dialdehyde ATP (oxidized ATP) has been used extensively
      as a selective antagonist at P2X(7) receptors, although P2X(7)-independent
      actions on pro-inflammatory cytokine release have also been reported. Because
      P2X(7) receptors in astrocytes have been suggested as potential targets of anti
      inflammatory drug therapy, we examined the effect of oxidized ATP on beta-actin
      expression and superoxide production of RBA-2 type-2 astrocytes known to possess
      P2X(7) receptors. Oxidized ATP per se decreased beta-actin expression time and
      dose dependently. Treatment with oxidized ATP for 8 h caused an approximately 50%
      decrease in beta-actin expression whereas other P2 receptor antagonists,
      brilliant blue G (BBG), suramin and pyridoxal phosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS), were not effective. In addition, oxidized ATP per se
      decreased the intracellular superoxide concentration, whereas ATP and the P2X(7)
      receptor-selective agonist 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate
      (BzATP) stimulated intracellular superoxide production, an effect inhibited by
      oxidized ATP. In addition, oxidized ATP neither affected cellular viability nor
      affected interleukin-1beta, converting enzyme (ICE)-like protease activity in
      these astrocytes. To further elucidate the mechanism, the effects of oxidized ATP
      on intracellular superoxide concentration and beta-actin expression were examined
      in a P2X(7) receptor-negative astrocyte cell line, IA-1g1. Oxidized ATP-induced a
      time-dependent decrease in intracellular superoxide concentration whereas
      oxidized ATP had no effect on beta-actin expression. Nevertheless, oxidized ATP
      altered f-actin cytoskeleton arrangement in IA-1g1 astrocytes. Taken together,
      these results indicate that oxidized ATP per se caused a cell specific decrease
      in beta-actin expression in RBA-2 type-2 astrocytes. In addition, oxidized ATP
      decreased intracellular superoxide concentrations and altered f-actin
      cytoskeleton arrangement in both P2X(7) receptor-positive and -negative
      astrocytes. Thus, we conclude from these results that the effects of oxidized ATP
      on actin and superoxide are mediated through mechanisms that are at least in
      part, independent of P2X(7) receptors.

PMID- 17020760
TI  - Homocysteine regulates expression of Herp by DNA methylation involving the AARE
      and CREB binding sites.
AB  - Herp (homocysteine-induced endoplasmic reticulum protein) is an ER-resident
      membrane protein, which has a ubiquitin-like domain at its N-terminus. Expression
      of Herp protein is up-regulated in response to ER stress, including homocysteine.
      Herp stabilizes neuronal Ca(2+) homeostasis and is involved in improving the
      balance of the folding capacity and protein loading in the ER. In patients with
      alcoholism, we observed a significant decrease in Herp mRNA expression, and an
      increase of Herp promoter DNA methylation, which was associated with elevated
      homocysteine levels. Therefore, we studied the mechanism of Herp CpG islands
      regulation by luciferase assays and mRNA analysis in neuronal SH-SY5Y (human
      neuroblastoma cell line) and HEK 293T (human embryonic kidney 293T) cells. Acute
      homocysteine treatment caused transient demethylation of the Herp promoter and an
      increase in Herp mRNA level. Global DNA methylation was increased over the
      following 48 h period. We identified the transcription factor binding site AARE
      (amino acid response element) by mutational analysis involved in Herp induction
      in SH-SY5Y cells, and the more significant role of the CREB binding site (cyclic
      AMP response element-binding protein) compared to AARE in HEK 293T cells.
      Stimulation with SAM (S-adenosyl methionine) and homocysteine led to an increase
      in Herp promoter methylation, which correlated to an acute decrease in luciferase
      expression in SAM, but not in homocysteine stimulated cells. Complete methylation
      of the CpG islands resulted in suppressed gene expression.

PMID- 17020761
TI  - Female rats exhibit a conditioned place preference for nonpaced mating.
AB  - Paced, but not nonpaced, mating behavior is reported to induce a conditioned
      place preference (CPP) in female rats. Contrary to these previous findings,
      Experiment 1 showed that female rats that received 15 intromissions from a single
      male rat during each of five conditioning sessions exhibited a CPP for the
      compartment associated with mating when the intromissions were delivered via a
      paced or nonpaced paradigm. Experiment 2 demonstrated that nonpaced mating
      induced a CPP when a single male delivered the 15 intromissions but not when the
      male was replaced following ejaculation and a new male allowed to complete the
      requisite number of intromissions. These findings invite reevaluation of the
      reinforcing aspects of mating behavior in female rats.

PMID- 17020762
TI  - A one-step real-time PCR assay for detection of DQA1*05, DQB1*02 and DQB1*0302 to
      aid diagnosis of celiac disease.
AB  - Celiac disease is an autoimmune disorder that develops after dietary exposure of
      the small intestine to gluten peptides in cereals. Celiac disease has a strong
      genetic component associated with HLA-DQ2 and HLA-DQ8, and testing for absence of
      these genetic markers is useful when serological tests and biopsies are
      indeterminate, as it renders celiac disease highly unlikely. We have developed a
      new real-time PCR assay, using sequence-specific primers (PCR-SSP) and TaqMan
      probes, for detection of DQB1*05, DQB1*02 (coding for DQ2) and DQB1*0302 (coding
      for DQ8). PCR amplification and detection of DQ2 and DQ8 was accurately and
      unambiguously performed from genomic DNA isolated from cell lines and human DNA.
      Amplification was scored digitally, without laboratory manipulation of amplified
      PCR products and with a higher accuracy than PCR-SSP. This assay should increase
      accuracy and throughput, and reduce risks of contamination in laboratories where
      testing for HLA DQ2 and DQ8 is performed as part of diagnosis of celiac disease.

PMID- 17020763
TI  - Differential gene expression profiling in genetic and multifactorial
      cardiovascular diseases.
AB  - Gene expression profiling by microarray technologies has been successfully
      applied to study the transcriptional changes that occur in tissues such as heart,
      vessels and blood cells in different cardiovascular disorders. Such studies have
      been performed in human cardiovascular syndromes and in animal models with the
      aim of unraveling the complex molecular pictures underlying human
      pathophysiology. As already observed in cancer research, gene expression studies
      in humans may provide a finer molecular classification of patients with
      cardiovascular diseases and indicate new markers useful for prognostic and
      therapeutic strategies. In this paper, we present the findings obtained with
      microarray platforms to explore transcriptome alterations in cardiovascular
      diseases. To describe the potential of global expression profiling approach in
      this field, we have chosen to review the genomic findings obtained in some
      classic heart diseases with genetic transmission such as hyperthrophic
      cardiomyopathy and Fabry disease, together with findings obtained in common
      multifactorial cardiovascular disorders such as heart failure, atherosclerosis
      and infarction. Wherever feasible, we present the results obtained in patients
      together with those obtained in the corresponding animal and cellular models.

PMID- 17020764
TI  - Competition between acetate and oleate for the formation of malonyl-CoA and
      mitochondrial acetyl-CoA in the perfused rat heart.
AB  - We previously showed that, in the perfused rat heart, the capacity of n-fatty
      acids to generate mitochondrial acetyl-CoA decreases as their chain length
      increases. In the present study, we investigated whether the oxidation of a long
      chain fatty acid, oleate, is inhibited by short-chain fatty acids, acetate or
      propionate (which do and do not generate mitochondrial acetyl-CoA, respectively).
      We perfused rat hearts with buffer containing 4 mM glucose, 0.2 mM pyruvate, 1 mM
      lactate, and various concentrations of either (i) [U-(13)C]acetate, (ii) [U
      (13)C]acetate plus [1-(13)C]oleate, or (iii) unlabeled propionate plus [1
      (13)C]oleate. Using mass isotopomer analysis, we determined the contributions of
      the labeled substrates to the acetyl moiety of citrate (a probe of mitochondrial
      acetyl-CoA) and to malonyl-CoA. We found that acetate, even at low concentration,
      markedly inhibits the oxidation of [1-(13)C]oleate in the heart, without change
      in malonyl-CoA concentration. We also found that propionate, at a concentration
      higher than 1 mM, decreases (i) the contribution of [1-(13)C]oleate to
      mitochondrial acetyl-CoA and (ii) malonyl-CoA concentration. The inhibition by
      acetate or propionate of acetyl-CoA production from oleate probably results from
      a competition for mitochondrial CoA between the CoA-utilizing enzymes.

PMID- 17020765
TI  - Transmission electron microscopy reveals an optimal HIV-1 nucleocapsid
      aggregation with single-stranded nucleic acids and the mature HIV-1 nucleocapsid
      protein.
AB  - HIV-1 nucleocapsid protein (NCp7) condenses the viral RNA within the mature
      capsid. In a capsid-free system, NCp7 promotes an efficient mechanism of
      aggregation with both RNA and DNA. Here, we show an analysis of these
      macromolecular complexes by dark-field imaging using transmission electron
      microscopy. Thousands of mature NCp7 proteins co-aggregate with hundreds of
      single-stranded circular DNA molecules (ssDNA) within minutes, as observed with
      poly(rA). These co-aggregates are highly stable but dynamic structures, as they
      dissociate under harsh conditions, and after addition of potent ssDNA or NCp7
      competitive ligands. The N-terminal domain and zinc fingers of NCp7 are both
      required for efficient association. Addition of magnesium slightly increases the
      avidity of NCp7 for ssDNA, while it strongly inhibits co-aggregation with relaxed
      circular double-stranded DNA (dsDNA). This DNA selectivity is restricted to
      mature NCp7, compared to its precursors NCp15 and NCp9. Moreover, for NCp15, the
      linkage of NCp7 with the Gag C-terminal p6-peptide provokes a deficiency in ssDNA
      aggregation, but results in DNA spreading similar to prototypical SSB proteins.
      Finally, this co-aggregation is discussed in a dynamic architectural context with
      regard to the mature HIV-1 nucleocapsid. On the basis of the present data, we
      propose that condensation of encapsidated RNA requires the C-terminal processing
      of NCp. Subsequently, disassembly of the nucleocapsid should be favoured once
      dsDNA is produced by HIV-1 reverse transcriptase.

PMID- 17020767
TI  - Key role of coulombic interactions for the folding transition state of the cold
      shock protein.
AB  - The cold shock protein CspB shows a five-stranded beta-sheet structure, and it
      folds rapidly via a native-like transition state. A previous Phi value analysis
      showed that most of the residues with Phi values close to one reside in strand
      beta1, and two of them, Lys5 and Lys7 are partially exposed charged residues. To
      elucidate how coulombic interactions of these two residues contribute to the
      energetic organisation of the folding transition state we performed comparative
      folding experiments in the presence of an ionic denaturant (guanidinium chloride)
      and a non-ionic denaturant (urea) and a double-mutant analysis. Lys5 contributes
      6.6 kJ mol(-1) to the stability of the transition state, and half of it
      originates from screenable coulombic interactions. Lys7 contributes 5.3 kJ mol(
      1), and 3.4 kJ mol(-1) of it are screened by salt. In the folded protein Lys7
      interacts with Asp25, and the screenable coulombic interaction between these two
      residues is fully formed in the transition state. This suggests that long-range
      coulombic interactions such as those originating from Lys5 and Lys7 of CspB can
      be important for organizing and stabilizing native-like structure early in
      protein folding.

PMID- 17020766
TI  - Crystal structure of the human prostacyclin synthase.
AB  - Prostacyclin synthase (PGIS) catalyzes an isomerization of prostaglandin H(2) to
      prostacyclin, a potent mediator of vasodilation and anti-platelet aggregation.
      Here, we report the crystal structure of human PGIS at 2.15 A resolution, which
      represents the first three-dimensional structure of a class III cytochrome P450.
      While notable sequence divergence has been recognized between PGIS and other
      P450s, PGIS exhibits the typical triangular prism-shaped P450 fold with only
      moderate structural differences. The conserved acid-alcohol pair in the I helix
      of P450s is replaced by residues G286 and N287 in PGIS, but the distinctive
      disruption of the I helix and the presence of a nearby water channel remain
      conserved. The side-chain of N287 appears to be positioned to facilitate the
      endoperoxide bond cleavage, suggesting a functional conservation of this residue
      in O-O bond cleavage. A combination of bent I helix and tilted B' helix creates a
      channel extending from the heme distal pocket, which seemingly allows binding of
      various ligands; however, residue W282, placed in this channel at a distance of
      8.4 A from the iron with its indole side-chain lying parallel with the porphyrin
      plane, may serve as a threshold to exclude most ligands from binding.
      Additionally, a long "meander" region protruding from the protein surface may
      impede electron transfer. Although the primary sequence of the PGIS cysteine
      ligand loop diverges significantly from the consensus, conserved tertiary
      structure and hydrogen bonding pattern are observed for this region. The
      substrate-binding model was constructed and the structural basis for prostacyclin
      biosynthesis is discussed.

PMID- 17020768
TI  - Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium
      tuberculosis.
AB  - The structural mechanism of the catalytic functioning of shikimate kinase from
      Mycobacterium tuberculosis was investigated on the basis of a series of high
      resolution crystal structures corresponding to individual steps in the enzymatic
      reaction. The catalytic turnover of shikimate and ATP into the products shikimate
      3-phosphate and ADP, followed by release of ADP, was studied in the crystalline
      environment. Based on a comparison of the structural states before initiation of
      the reaction and immediately after the catalytic step, we derived a structural
      model of the transition state that suggests that phosphoryl transfer proceeds
      with inversion by an in-line associative mechanism. The random sequential binding
      of shikimate and nucleotides is associated with domain movements. We identified a
      synergic mechanism by which binding of the first substrate may enhance the
      affinity for the second substrate.

PMID- 17020769
TI  - Structure, dynamics and heparin binding of the C-terminal domain of insulin-like
      growth factor-binding protein-2 (IGFBP-2).
AB  - Insulin-like growth factor-binding protein-2 (IGFBP-2) is the largest member of a
      family of six proteins (IGFBP-1 to 6) that bind insulin-like growth factors I and
      II (IGF-I/II) with high affinity. In addition to regulating IGF actions, IGFBPs
      have IGF-independent functions. The C-terminal domains of IGFBPs contribute to
      high-affinity IGF binding, and confer binding specificity and have overlapping
      but variable interactions with many other molecules. Using nuclear magnetic
      resonance (NMR) spectroscopy, we have determined the solution structure of the C
      terminal domain of IGFBP-2 (C-BP-2) and analysed its backbone dynamics based on
      15N relaxation parameters. C-BP-2 has a thyroglobulin type 1 fold consisting of
      an alpha-helix, a three-stranded anti-parallel beta-sheet and three flexible
      loops. Compared to C-BP-6 and C-BP-1, structural differences that may affect IGF
      binding and underlie other functional differences were found. C-BP-2 has a longer
      disordered loop I, and an extended C-terminal tail, which is unstructured and
      very mobile. The length of the helix is identical with that of C-BP-6 but shorter
      than that of C-BP-1. Reduced spectral density mapping analysis showed that C-BP-2
      possesses significant rapid motion in the loops and termini, and may undergo
      slower conformational or chemical exchange in the structured core and loop II. An
      RGD motif is located in a solvent-exposed turn. A pH-dependent heparin-binding
      site on C-BP-2 has been identified. Protonation of two histidine residues, His271
      and His228, seems to be important for this binding, which occurs at slightly
      acidic pH (6.0) and is more significant at pH 5.5, but is largely suppressed at
      pH 7.4. Possible preferential binding of IGFBP-2 and its C- domain fragments to
      glycosaminoglycans in the acidic extracellular matrix (ECM) of tumours may be
      related to their roles in cancer.

PMID- 17020770
TI  - New findings regarding the significance of pavement skid resistance for road
      safety on Swiss freeways.
AB  - INTRODUCTION: The significance of the influence of poor pavement skid resistance
      values on accident frequency in wet pavement conditions has been the object of
      many studies over several years. The various investigations have produced very
      diverse findings. Only seldom, however, has detailed consideration been given to
      the central question of whether pavement skid resistance is a decisive parameter
      in the occurrence of local accident "black spots." Until now, the focus has been
      more on describing a relationship between pavement skid resistance and accident
      frequency. METHOD AND RESULTS: In the course of the network-wide survey of the
      states of pavements and of accident occurrence on Switzerland's freeways from
      1999 to 2003, it emerged that a relationship with inadequate pavement skid
      resistance was provable for only a small proportion of accident black spots.
      These findings were used to frame a guideline for authorities and highway
      operators about how to treat skid resistance when assessing pavements and
      accident occurrence on freeways.

PMID- 17020771
TI  - Fatal crashes involving young unlicensed drivers in the U.S.
AB  - INTRODUCTION: Young unlicensed drivers' involvement in fatal crashes is a
      recurrent problem in the United States. METHODS: This descriptive study extracted
      cross-sectional data on fatal crashes from the Fatality Analysis Reporting System
      from 1998 to 2002. Young unlicensed driver fatal crashes are examined by age,
      gender, and region. RESULTS: There were 2,452 young unlicensed driver fatal
      crashes representing 10.8% of all young drivers' fatal crashes. By age, 72.5% are
      over 15 years, males are involved in 74.5%, and southern and western states have
      a higher percent of young unlicensed driver fatal crashes. CONCLUSIONS: Subgroups
      of young people based on their age, gender, and region are over-represented in
      fatal crashes as unlicensed drivers. Further studies are needed to investigate
      the context and factors of young unlicensed drivers, essential to tailor
      interventions. IMPACT ON INDUSTRY: Young unlicensed drivers circumvent the
      established licensing process and pose a serious threat to themselves and other
      road users.

PMID- 17020772
TI  - Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of
      low-protein pregnancies.
AB  - We investigated the effect of fish oil (FO) treatment on cardiorenal structure of
      adult offspring from low-protein pregnancies. Three month old offspring were
      assigned to eight groups (four male groups and four female groups, n=8 each)
      (NP=normal-protein diet, LP=low-protein diet): NP, LP, NP plus FO, and LP plus
      FO. Left ventricle and kidney were analyzed with light microscopy and stereology.
      The both sexes of LP offspring showed 30% lower birth weights than the respective
      NP offspring and high blood pressure (BP) levels in adulthood which was
      efficiently reduced by FO treatment. In the heart, FO treated the cardiomyocyte
      hypertrophy, the vascularization impairment, and decreased the cardiomyocyte loss
      usually observed in adult LP offspring. In the kidney, FO treated, in the male,
      the imbalance of the cortex-to-medulla ratio observed in both sexes of LP
      offspring, and reduced the glomeruli loss in the LP offspring. The positive
      correlation between the number of cardiomyocyte nuclei later in life and the body
      mass (BM) at birth was significant only in both sexes of LP offspring and this
      correlation disappeared in LP plus fish oil offspring. The positive correlation
      between the number of glomeruli later in life and the BM at birth was significant
      in NP male offspring and in both sexes of LP offspring. In conclusion, FO
      supplement, which is a rich source of n-3 fatty acids (DHA and EPA), has
      beneficial effects on BP control and cardiac and renal adverse remodeling usually
      seen in offspring of the LP pregnancies.

PMID- 17020773
TI  - Up-regulation by zinc of FGF-2-induced VEGF release through enhancing p44/p42 MAP
      kinase activation in osteoblasts.
AB  - We previously reported that basic fibroblast growth factor (FGF-2) activates
      stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42
      mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular
      endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells. In
      the present study, we investigated whether zinc affects the VEGF release by FGF-2
      in MC3T3-E1 cells. The FGF-2-induced VEGF release was significantly enhanced by
      ZnSO(4) but not Na(2)SO(4). The enhancing effect of ZnSO(4) was dose-dependent
      between 1 and 100 muM. ZnSO(4) markedly enhanced the FGF-2-induced
      phosphorylation of p44/p42 MAP kinase while having little effect on the SAPK/JNK
      phosphorylation. PD98059 significantly reduced the amplification by ZnSO(4) of
      the FGF-2-stimulated VEGF release. Taken together, our findings strongly suggest
      that zinc enhances FGF-2-stimulated VEGF release resulting from up-regulating
      activation of p44/p42 MAP kinase in osteoblasts.

PMID- 17020774
TI  - Anxiolytic-like effect of group III mGlu receptor antagonist is serotonin
      dependent.
AB  - Literature data have provided evidence that antagonists of group I metabotropic
      glutamate receptors (mGluRs) and agonists of group II/III mGluRs show anxiolytic
      like properties in preclinical studies. However data reporting anxiolytic-like
      action of group III mGlu receptor antagonists were also published. In the present
      paper we investigated the anxiolytic-like activity of the group III mGlu receptor
      antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG). To examine its
      anxiolytic-like effects, the basolateral amygdala was chosen as an injection
      site, as this brain region is involved in the regulation of anxiety-related
      behavior. To detect anxiolytic-like activity, the Vogel conflict-drinking test in
      rats was used. Intra-amygdalar injections of CPPG exhibited dose-dependent,
      potent anxiolytic-like action at a dose of 75 nmol, which was blocked by a
      concomitant administration of the group III mGlu receptor agonist CI (S,3R,4S)-1
      aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I) at a dose of 7.5 nmol. The
      benzodiazepine receptor antagonist flumazenil (given intraperitoneally, 10 mg/kg)
      did not change the anxiolytic-like effect of CPPG, but that effect was abolished
      by the non-selective antagonist of 5-HT receptors metergoline and the antagonist
      of 5-HT2A/C receptors ritanserin (both given intraperitoneally at doses of 2 and
      0.5 mg/kg, respectively). These findings suggest that the blockade of group III
      mGlu receptors in the amygdala is responsible for anxiolysis and that
      serotonergic, but not the benzodiazepine recognition site of the GABA-ergic
      system are involved in the anxiolytic-like response induced by group III mGlu
      antagonist.

PMID- 17020775
TI  - Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal
      and synaptic vesicle accumulation and release of dopamine and noradrenaline in
      vitro in the rat brain.
AB  - D- and L-amphetamine sulphate isomers, methylphenidate and atomoxetine, are
      effective treatments for attention-deficit hyperactivity disorder (ADHD). This
      study provides a detailed comparison of their effects on the synaptosomal and
      vesicular accumulation of dopamine (DA) and noradrenaline (NA) and release in
      vitro in rat prefrontal cortex and striatum. D-amphetamine was more potent than L
      amphetamine at inhibiting accumulation of DA or NA in synaptosomes and vesicles.
      All drugs were weaker at inhibiting the accumulation of vesicular DA and NA
      compared to synaptosomal accumulation and more potently inhibited NA accumulation
      than DA. Methylphenidate was weak at inhibiting vesicular accumulation of DA and
      NA compared to its potent synaptosomal effects. The D-isomer had greater potency
      than the L-isomer on basal and electrically stimulated striatal DA release;
      however the L-isomer was 2-fold more potent than the D-isomer on basal fronto
      cortical NA release. The selective DA reuptake inhibitor, GBR-12909 and NA
      reuptake inhibitors, maprotiline and atomoxetine, had different release profiles
      both on the potency and magnitude of basal and stimulated DA and NA release
      compared to the amphetamine isomers. These results identify distinct
      pharmacological action by the amphetamine isomers on dopaminergic and
      noradrenergic neurotransmission, which may impact on their therapeutic effects in
      the treatment of ADHD.

PMID- 17020776
TI  - Mole-rats from higher altitudes have greater thermoregulatory capabilities.
AB  - Subterranean mammals (those that live and forage underground) inhabit a
      challenging microenvironment, with high levels of carbon dioxide and low levels
      of oxygen. Consequently, they have evolved specialised morphological and
      physiological adaptations. For small mammals that inhabit high altitudes, the
      effects of cold are compounded by low oxygen partial pressures. Hence,
      subterranean mammals living at high altitudes are faced with a uniquely demanding
      physiological environment, which presumably necessitates additional physiological
      adjustments. We examined the thermoregulatory capabilities of two populations of
      Lesotho mole-rat Cryptomys hottentotus mahali that inhabit a 'low' (1600 m) and a
      'high' (3200 m) altitude. Mole-rats from the high altitude had a lower
      temperature of the lower critical point, a broader thermoneutral zone, a lower
      thermal conductance and greater regulatory non-shivering thermogenesis than
      animals from the lower altitude. However, minimum resting metabolic rate values
      were not significantly different between the populations and were low compared
      with allometric predictions. We suggest that thermoregulatory costs may in part
      be met by animals maintaining a low resting metabolic rate. High-altitude animals
      may adjust to their cooler, more oxygen-deficient environment by having an
      increased non-shivering thermogenesis whilst maintaining low thermal conductance.

PMID- 17020777
TI  - DNA vaccines against dengue virus based on the ns1 gene: the influence of
      different signal sequences on the protein expression and its correlation to the
      immune response elicited in mice.
AB  - We analyzed four DNA vaccines based on DENV-2 NS1: pcENS1, encoding the C
      terminal from E protein plus the NS1 region; pcENS1ANC, similar to pcENS1 plus
      the N-terminal sequence from NS2a (ANC); pcTPANS1, coding the t-PA signal
      sequence fused to NS1; and pcTPANS1ANC, similar to pcTPANS1 plus the ANC
      sequence. The NS1 was detected in lysates and culture supernatants from pcTPANS1
      , pcENS1- and pcENS1ANC-transfected cells and not in cells with pcTPANS1ANC. Only
      the pcENS1ANC leads the expression of NS1 in plasma membrane, confirming the
      importance of ANC sequence for targeting NS1 to cell surface. High levels of
      antibodies recognizing conformational epitopes of NS1 were induced in mice
      immunized with pcTPANS1 and pcENS1, while only few pcENS1ANC-inoculated animals
      presented detectable anti-NS1 IgG. Protection against DENV-2 was verified in
      pcTPANS1- and pcENS1-immunized mice, although the plasmid pcTPANS1 induced slight
      higher protective immunity. These plasmids seem to activate distinct patterns of
      the immune system.

PMID- 17020778
TI  - Protein microarrays for the detection of biomarkers in head and neck squamous
      cell carcinomas.
AB  - Protein microarrays are of increasing importance for high-throughput screening of
      fresh tissues. In our study, protein microarrays were generated by printing
      antibodies onto membranes to characterize protein profiles expressed by head and
      neck squamous cell carcinomas (HNSCCs). Cellular proteomes of 30 matched normal
      squamous epithelial cells and carcinoma specimens were analyzed after tissue
      microdissection using microarrays composed of 83 different antibodies. As
      controls, Western blot analysis and tissue microarrays (TMAs) containing 98 HNSCC
      specimens were used. Of the 83 proteins examined, 14 showed differential
      expression between HNSCCs and normal epithelium. The protein microarray approach
      revealed an upregulation of 8 proteins and a downregulation of 6 proteins. Bag-1,
      Cox-2, Hsp-70, Stat3, pescadillo, MMP-7 (matrilysin), IGF-2, and cyclin D1 were
      identified to be significantly upregulated, whereas suppressor of cytokine
      signaling 1, thrombospondin, TGF-beta1, Jun, Fos, and Fra-2 were downregulated.
      The differential expression of these proteins was confirmed using Western blot
      and TMA. Upon correlation of differentially regulated proteins with the
      clinicopathologic data of our patients, MMP-7 (matrilysin) was found to be
      associated with survival in univariate, but not multivariate, analysis. These
      data indicate that our protein arrays provide protein information in a
      systematic, reproducible, and also high-throughput fashion.

PMID- 17020779
TI  - Prognostic value of humbug gene overexpression in stage II colon cancer.
AB  - Overexpression of aspartyl (asparaginyl) beta-hydroxylase (AAH) has been
      demonstrated in hepatocellular carcinoma, cholangiocarcinoma, and pancreatic
      carcinoma. AAH has an important role in regulating cell motility and
      invasiveness. Humbug is a truncated homolog of AAH, with a role in calcium
      regulation. The present study examines the prognostic use of AAH and humbug gene
      expression in stage II colon cancer. One hundred thirty cases of TNM stage II
      colon carcinoma were retrieved from the Rhode Island Hospital pathology archives.
      Tissue microarrays were immunostained with the FB50 and 15C7 monoclonal
      antibodies generated to recombinant AAH. However, FB50 also recognizes humbug. In
      addition, AAH and humbug expression was analyzed in samples of colon cancer and
      adjacent normal mucosa by real-time quantitative reverse transcriptase-polymerase
      chain reaction. Humbug (FB50) expression was localized to the tumor cytoplasm,
      whereas normal colonic epithelium did not exhibit significant immunoreactivity.
      Humbug staining was detected in 85% of the neoplasms, 23% of which stained
      strongly. Strong humbug immunoreactivity positively correlated with nuclear grade
      (P = .006) and inversely with survival (P = .027). In contrast to humbug, AAH
      (15C7) immunoreactivity was seen in normal and neoplastic epithelium. There was
      no correlation between AAH immunoreactivity and tumor grade, or survival.
      Correspondingly, reverse transcriptase-polymerase chain reaction studies
      demonstrated up-regulation of humbug but not AAH in 95% of colon carcinomas
      relative to adjacent colon cancer-free mucosa (P < .0001). This study
      demonstrates that high levels of humbug immunoreactivity in colon carcinomas
      correlate with histologic grade and tumor behavior, suggesting that humbug can
      serve as a prognostic biomarker of TNM stage II colon cancers. In addition,
      molecular studies demonstrated that the increased levels of FB50 detected were
      due to humbug, as opposed to AAH overexpression.

PMID- 17020780
TI  - Focal segmental glomerulosclerosis after membranous glomerulonephritis in
      remission: temporal diversity of glomerulopathy after bone marrow
      transplantation.
AB  - Heavy proteinuria after bone marrow transplantation (BMT) is rare. Pathology
      shows membranous glomerulonephritis (MGN) in most cases. After BMT, focal
      segmental glomerulosclerosis (FSGS) after resolution of MGN has not been
      reported. We describe a 13-year-old boy who had matched unrelated donor
      allogeneic BMT for relapsed acute lymphoblastic leukemia, complicated by chronic
      graft-versus-host disease. Nephrotic syndrome developed 1 year after BMT and
      renal biopsy revealed MGN. Immunosuppressive therapy achieved good clinical
      remission, and treatment was stopped after 15 months. He developed significant
      proteinuria 55 months later. The second renal biopsy showed FSGS without changes
      of MGN. This distinctive disease evolution gives inspiring implications. Complete
      morphological resolution of graft-versus-host disease-associated MGN, achieved in
      our case, has not been previously documented. Recurrent significant proteinuria
      after BMT is not necessarily due to previous renal lesion, and a repeat renal
      biopsy is indicated. The pathogenesis of MGN and FSGS are different, and
      different mechanisms of glomerular injury can interplay in a single patient after
      BMT. This case helps to expand our knowledge of the temporal morphological
      spectrum of renal lesions associated with BMT.

PMID- 17020781
TI  - Effects of higenamine and its 1-naphthyl analogs, YS-49 and YS-51, on platelet
      TXA2 synthesis and aggregation.
AB  - The effects of higenamine and its 1-naphthyl analogs, YS-49 and YS-51, on
      thromboxane A(2) (TXA(2)) formation from arachidonic acid (AA) and aggregation in
      platelets, were investigated. YS-49 and YS-51 (IC(50); 32.8 and 39.4 microM
      respectively) exhibited much stronger inhibitory effects on TXA(2) formation than
      higenamine (IC(50); 2.99 mM). The higher inhibitory potencies of YS-49 and YS-51
      (IC(50): 3.3 and 5.7 microM respectively) than higenamine (IC(50): 140 microM) on
      AA induced rat platelet aggregation was presumed to be the result of low
      inhibitory effect of higenamine than YS-49 and YS-51 on TXA(2) production from
      AA. Among the present three compounds, the more hydrophobic naphthylmethyl groups
      were supposed to be more favorable than p-hydroxybenzyl moiety, at 1-position of
      the tetrahydroisoquinoline ring, to display the inhibitory effects on TXA(2)
      production and AA induced aggregation of platelets. In addition, higenamine, YS
      49 and YS-51 were observed directly antagonistic on TXA(2) receptor (TP
      receptors) by displaying inhibitory effects to U46619 (TXA(2) mimetic) induced
      platelet aggregation, however all of the three compounds showed similar order of
      inhibitory potencies. The present results are suggestive that YS-49 and YS-51
      exert their inhibitory effects on AA-induced platelet aggregation partly by
      inhibiting the production of TXA(2) from AA and partly by directly blocking the
      TP receptor, in addition to the previously reported effects on alpha(2)
      adrenergic receptor. On the other hand, higenamine is supposed to antagonize AA
      induced platelet aggregation by mostly directly blocking the TP receptor.

PMID- 17020782
TI  - Antiphospholipid antibody ELISAs: survey on the performance of clinical
      laboratories assessed by using lyophilized affinity-purified IgG with
      anticardiolipin and anti-beta2-Glycoprotein I activity.
AB  - Lupus anticoagulant (LA) and anticardiolipin (aCL) antibodies are the classical
      tests used to diagnose the antiphospholipid syndrome (APS). Unfortunately, since
      these are nonspecific and standardization is lacking, the results of laboratory
      work-ups upon which diagnosis are made are often misleading. The performance of
      clinical laboratories in detecting LA using lyophilised affinity purified
      immunoglobulin has been previously reported. The same material was used to
      investigate the inter-laboratory variability of aCL and anti-beta(2)-Glycoprotein
      I (beta(2)-GPI) antibody measurements. Laboratories were asked to test normal
      plasma spiked with purified IgG or distilled water in order to obtain 3 samples
      positive for aCL and anti-beta(2)-GPI at different antibody concentration (A, B
      and C) and 3 samples of normal plasma. Thirty-five laboratories participated and
      interpreted their test results. All performed an ELISA for IgG aCL antibodies,
      while 17 also tested samples using IgG anti-beta(2)-GPI antibody ELISA.
      Sensitivity and specificity were calculated on the basis of the responses
      provided by each laboratory. Overall, 99/105 samples were correctly interpreted
      as positive and 97/101 as negative for the presence of IgG aCL, corresponding to
      a sensitivity and specificity of 94% and 96%, respectively. Likewise, 46/51
      samples were correctly defined as positive and 50/51 as negative for the presence
      of IgG anti-beta(2)-GPI corresponding to a sensitivity and specificity of 90% and
      98%, respectively. A wide variability in results pertaining to the positive
      samples was found for aCL-ELISA (coefficient of variation of 79%, 59%, and 53%
      for samples A, B, and C, respectively) as well as for abeta(2)-GPI-ELISA
      (coefficient of variation of 85%, 95%, and 50% for samples A, B, and C,
      respectively). This was confirmed when the analysis was restricted to those
      centres using the same commercial kit. Median antibody concentrations reported by
      centres for positive samples were consistent with the prolongation of coagulation
      tests assessing lupus anticoagulant (LA). Among these, dRVVT showed a good
      sensitivity and linear correlation with aCL antibody concentration. In
      conclusion, on the whole this survey found correct interpretation of positive and
      negative samples by both ELISAs. Nonetheless the high variability of reported
      data remains a major problem that only a consensus on the part of laboratories
      and manufacturers to utilize standard, uniform materials and procedures can hope
      to overcome.

PMID- 17020783
TI  - BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls,
      limitations, and validation.
AB  - Bromodeoxyuridine (BrdU) is a thymidine analog that incorporates DNA of dividing
      cells during the S-phase of the cell cycle. As such, BrdU is used for birth
      dating and monitoring cell proliferation. BrdU immunohistochemistry has been
      instrumental for the study of the development of the nervous system, and to
      confirm that neurogenesis occurs in the adult mammalian brain, including in
      human. However, the use of BrdU for studying neurogenesis is not without pitfalls
      and limitations. BrdU is a toxic and mutagenic substance. It triggers cell death,
      the formation of teratomas, alters DNA stability, lengthens the cell cycle, and
      has mitogenic, transcriptional and translational effects on cells that
      incorporate it. All of which have profound consequences on neurogenesis. BrdU is
      not a marker of the S-phase of the cell cycle. As a thymidine analog, it is a
      marker of DNA synthesis. Therefore, studying neurogenesis with BrdU requires
      distinguishing cell proliferation and neurogenesis from other events involving
      DNA synthesis, like DNA repair, abortive cell cycle reentry and gene duplication.
      BrdU labeling is currently the most used technique for studying adult
      neurogenesis in situ. However in many instances, appropriate controls have been
      overlooked and events reported as the generation of new neuronal cells in the
      adult brain misinterpreted, which makes BrdU labeling one of the most misused
      techniques in neuroscience.

PMID- 17020784
TI  - Determinants of early identification of suicidal ideation in patients treated
      with antidepressants or anxiolytics in general practice: a multilevel analysis.
AB  - BACKGROUND: General practitioners (GPs) play a key role in identifying and
      managing patients with suicidal tendencies. Few studies, however, examine both GP
      and patient characteristics and GP practices associated with suicide assessment.
      This article aims to evaluate 1) GPs' success in early identification of suicidal
      ideation (SI) in patients starting antidepressant or anxiolytic treatment, and 2)
      patient- and GP-related factors associated with this success. METHODS: Survey of
      144 GPs practising in southeastern France and of consecutive adults consulting
      them during June-October 2004 and prescribed antidepressant or anxiolytic
      treatment. Data were collected from GPs (consultation-questionnaires focusing on
      their prescription, diagnosis and detection of SI) and patients (self
      administered questionnaires including the Hospital Anxiety and Depression scale
      and social and demographic characteristics). We used multilevel logistic
      regression to analyse factors associated with SI detection. RESULTS: GPs
      completed consultation-questionnaires for 713 patients, 405 of whom completed
      self-administered questionnaires. Eighty-nine patients (22%) reported SI; in 43
      cases (48%) SI had not been detected by the GP. GPs detected SI more frequently
      when they had completed continuing medical education about depression, when
      patients had higher depressive symptom scores, and when consultations were
      relatively long. LIMITATIONS: Study limited to patients receiving initial
      prescriptions for antidepressants or anxiolytics. CONCLUSIONS: The percentage of
      undetected SI in this study population was high. Additional training of GPs
      increases the chances of detecting SI. Medical training and continuing medical
      education should include better instruction about SI risk factors and diagnosis,
      including non-major depressions, and stress that screening requires sufficient
      consultation time.

PMID- 17020785
TI  - Association analysis of the LAG3 and CD4 genes in multiple sclerosis in two
      independent populations.
AB  - We have investigated the genetic involvement of the CD4 and the LAG3 genes, two
      appealing candidates for MS due to their suggested role in MS pathology. We
      genotyped a Swedish case-control material consisting of 920 MS patients and 778
      controls in an initial study of CD4, three SNPs showed a significant association
      with MS. An independent material consisting of 1720 Nordic MS patients and 1416
      controls were used for confirmation of associated markers in CD4 and to do a
      confirmative study of the LAG3 gene from previous findings. The result, including
      a total of 2640 MS patients and 2194 controls shows no significant association
      with CD4 and LAG3 and MS. We conclude that these genes are of minor importance in
      regard of genetic predisposition to the MS.

PMID- 17020786
TI  - Targeting signals in peroxisomal membrane proteins.
AB  - Peroxisomal membrane proteins (PMPs) are encoded by the nuclear genome and
      translated on cytoplasmic ribosomes. Newly synthesized PMPs can be targeted
      directly from the cytoplasm to peroxisomes or travel to peroxisomes via the
      endoplasmic reticulum (ER). The mechanisms responsible for the targeting of these
      proteins to the peroxisomal membrane are still rather poorly understood. However,
      it is clear that the trafficking of PMPs to peroxisomes depends on the presence
      of cis-acting targeting signals, called mPTSs. These mPTSs show great variability
      both in the identity and number of requisite residues. An emerging view is that
      mPTSs consist of at least two functionally distinct domains: a targeting element,
      which directs the newly synthesized PMP from the cytoplasm to its target
      membrane, and a membrane-anchoring sequence, which is required for the permanent
      insertion of the protein into the peroxisomal membrane. In this review, we
      summarize our knowledge of the mPTSs currently identified.

PMID- 17020787
TI  - Daily worry is related to low heart rate variability during waking and the
      subsequent nocturnal sleep period.
AB  - Stress and anxiety are risk factors for cardiovascular (CV) disease. Worry might
      be a mediator of their risks by prolonging their cognitive representation and
      concomitant CV activity. We hypothesized that daily stressors and worry, and
      trait anxiety and trait worry would be associated with high heart rate (HR) and
      low heart rate variability (HRV) during waking and the subsequent nocturnal sleep
      period, and that worry would mediate the effects of daily stressors. Low HRV and
      high HR are physiological risk factors for CV disease. Using an hourly diary,
      stressors, worry frequency and duration, and biobehavioral variables were
      measured during one day in 52 healthy subjects. During this time and the
      subsequent nocturnal sleep period, ambulatory ECG was measured. Stressors, worry
      and traits were related to higher HR and lower HRV during waking, and the effects
      of stressors and worry were extended into the sleeping period. Worry duration
      mediated the effects of stressors. The results were largely independent of
      biobehavioral variables including sleep quality. The results support the notion
      that worry, by prolonging CV activity, is a mediator of the CV risks of stress.
      They also imply a role for unconscious cognitive representation of stress.

PMID- 17020788
TI  - In vitro fermentation studies for selection and evaluation of Bacillus strains as
      starter cultures for the production of okpehe, a traditional African fermented
      condiment.
AB  - Selected Bacillus and Enterococcus strains, isolated from traditional okpehe
      fermentations, were studied for their suitability as starter cultures in
      laboratory-scale fermentations of Prosopis africana seeds for the production of
      okpehe, a traditional fermented vegetable product of Nigeria. The strains were
      selected on the basis of highest proteolytic activity, as determined with the
      APIZYM (BioMerieux) test. The choice of starter strains was narrowed to Bacillus
      subtilis strains BFE 5301 and BFE 5372. These were determined as the best starter
      combination because of rapid growth, high amylolytic and proteolytic activities,
      high levels of polyglutamic acid production by strain BFE 5372, as well as
      bacteriocin production by strain BFE 5301. Other mixed culture fermentations did
      not yield sensorically acceptable products. Although a monoculture fermentation,
      using only B. subtilis strain BFE 5372, produced okpehe with very good sensory
      characteristics, the growth of B. cereus could be detected after 48 h
      fermentation, indicating that this starter did not sufficiently contribute to
      product safety. Mixed culture fermentation with the combination of bacteriocin
      producing starter B. subtilis BFE 5301 and the non-bacteriocin-producing B.
      subtilis BFE 5372, produced a product with good sensory characteristics, in which
      growth of B. cereus was delayed. The bacteriocin produced by B. subtilis strain
      BFE 5301 was identified as subtilisin, using subtilisin-specific primers and PCR
      amplification of the subtilisin gene. The bacteriocin was heat-stable at 100
      degrees C for 10 min and exhibited highest activity at pH values lower or equal
      to pH 6.0. The bacteriocin was sensitive to the proteolytic enzymes trypsin and
      alpha-chymotrypsin at concentrations of 10 mg/ml.

PMID- 17020789
TI  - Clinical experience with risperidone in the treatment of behavioral and
      psychological symptoms of dementia.
AB  - Dementia is a neuropsychiatric disorder characterized by cognitive impairment and
      behavioral and psychological symptoms. The efficacy and tolerability of
      risperidone for treating dementia-associated psychological and behavioral
      disturbances were evaluated in a study of 135 patients aged 60-85 years with DSM
      IV diagnoses of Alzheimer's disease. All were treated with risperidone at a
      starting dose of 0.5 mg once daily at bedtime. After the first 3 days of therapy
      the dosage was increased to 1 mg in 2 doses (morning and evening), then a further
      0.5 mg was added (alternatively in the morning and in the evening) every three
      days until attenuation of the psychiatric symptoms. The response to treatment was
      evaluated for a period of 12 weeks by the Neuropsychiatric Inventory (NPI) and
      the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Both
      NPI and BEHAVE-AD were administered at the baseline visit, and after 4 and 12
      weeks of therapy. Tolerability was assessed by the incidence of clinically
      evident side effects. The mean dose at endpoint was 1 mg/day of risperidone. The
      mean NPI score was 28.80+/-13.92 at start, 15.55+/-11.25 after 4 weeks and 8.30+/
      7.00 at endpoint. The reduction in mean scores at 4 and 12 weeks was
      statistically significant in most of the Neuropsychiatric Inventory items, except
      for appetite disorders (p<0.0001). The mean BEHAVE-AD score was 20.44+/-3.92 at
      start, 13.50+/-11.39 after 4 weeks and 8.03+/-7.80 at endpoint. All the items
      showed a statistically significant improvement after 4 and 12 weeks (p<0.0001).
      The results were better at 12 than at 4 weeks. In our elderly patients with
      dementia low-dose risperidone was well tolerated and associated with reductions
      in BPSD, in particular agitation, aggression, irritability, delusions, sleep
      disorders, anxiety and phobias.

PMID- 17020790
TI  - Carboxylated chitooligosaccharides (CCOS) inhibit MMP-9 expression in human
      fibrosarcoma cells via down-regulation of AP-1.
AB  - Matrix metalloproteinases (MMPs) play a fundamental role in invasion and
      metastasis of tumor and, recent advances in medicinal chemistry have approached
      designing of MMP inhibitors with desired structural properties, selectivity and
      bioavailability. In the present study, novel low-molecular-weight carboxylated
      chitooligosaccharides (CCOS) were evaluated for their MMP-9 inhibitory effect on
      human fibrosarcoma cell line (HT1080). In zymography experiments, a clear dose
      dependent inhibition on MMP-9 mediated gelatinolytic activities were observed in
      HT1080 cells following treatment with CCOS. Further, transfection studies carried
      out with MMP-9 and AP-1 reporter constructs suggested that the observed reduction
      in MMP-9 expression was due to down-regulation of MMP-9 transcription that
      mediated via inhibition of AP-1. Moreover, expression of c-Fos protein levels in
      cytoplasm and nucleus confirmed that CCOS could inhibit AP-1 expression but not
      its translocation. However, in the presence of CCOS, NF-kappaB and TIMP-1
      expression levels remained constant. More importantly, inhibition of MMP-9
      expression clearly led to inhibit tumor invasiveness that was studied with
      reconstituted basement membrane matrix proteins coated synthetic membranes. Taken
      together, this study discusses MMP-9 inhibition potential of CCOS and their
      involvement to demote degradation and cellular invasion of extracellular matrix
      (ECM) and basement membrane. Thus, control of MMP-9 expression by CCOS has
      considerable significance for the regulation of tumor progression.

PMID- 17020791
TI  - A computational prediction of isochores based on hidden Markov models.
AB  - Mammalian genomes are organised into a mosaic of regions (in general more than
      300 kb in length), with differing, relatively homogeneous G+C contents. The G+C
      content is the basic characteristic of isochores, but they have also been
      associated with many other biological properties. For instance, the genes are
      more compact and their density is highest in G+C rich isochores. Various ways of
      locating isochores in the human genome have been developed, but such methods use
      only the base composition of the DNA sequences. The present paper proposes a new
      method, based on a hidden Markov model, which takes into account several of the
      biological properties associated with the isochore structure of a genome. This
      method leads to good segmentation of the human genome into isochores, and also
      permits a new analysis of the known heterogeneity of G+C rich isochores: most
      (60%) of the G+C poor genes embedded in G+C rich isochores have UTR sequences
      characteristic of G+C rich genes. This genomic feature is discussed in the
      context of both evolution and genome function.

PMID- 17020792
TI  - Identification and characterization of endoplasmic reticulum-associated protein,
      ERp43.
AB  - Disposal of misfolded proteins from the lumen of the endoplasmic reticulum (ER)
      is one of the quality control mechanisms present in the protein secretory
      pathway. Through ER-associated degradation, misfolded substrates are targeted to
      the cytosol where they are degraded by proteasomes. Here we describe the
      identification of a human ER-associated 43-kD protein (ERp43) by sequencing of
      the subtraction suppression hybridization cDNA library from ER stress-treated
      cells. The ERp43 gene encodes a protein of 383 amino acid residues that contains
      a potential transmembrane domain. Analysis revealed that ERp43 is primarily
      located in the ER. Quantitative reverse transcriptase-polymerase chain reaction
      demonstrated that gene expression was relatively high in the neuronal tissues and
      in the kidney, with ERp43 protein highly expressed in the spinal cord and in the
      kidney. In cultured cells, overexpression of ERp43 accelerated cell growth and
      inhibited ER stress-induced cell death, while down-regulation of ERp43 expression
      decreased proliferation rate and enhanced this type of cell death. These findings
      indicate that ERp43 plays important roles in cell growth and ER stress-induced
      cell death.

PMID- 17020793
TI  - Diagnostic performance of tests based on Trypanosoma cruzi excreted-secreted
      antigens in an endemic area for Chagas' disease in Bolivia.
AB  - The diagnostic performance of Trypanosoma cruzi excreted-secreted antigen (TESA)
      based and conventional tests for Chagas' disease was evaluated in a field study
      with 742 sera from a population in an endemic area in the Department of
      Chuquisaca, Bolivia. Of the 742 samples, 329 (44.34 %) were positive in the TESA
      blot assay, which diagnosed 9 Trypanosoma cruzi-infected individuals missed by
      conventional serologic tests.

PMID- 17020794
TI  - Pacemaker infection due to Mycobacterium fortuitum: the role of universal 16S
      rRNA gene PCR and sequencing.
AB  - Rapidly growing mycobacteria are a rare cause of pacemaker infection. A low index
      of suspicion and conventional diagnostic methods may delay diagnosis. We present
      a review of the literature and report a case of pacemaker infection due to
      Mycobacterium fortuitum rapidly detected by universal 16S rRNA gene polymerase
      chain reaction and sequencing.

PMID- 17020795
TI  - External quality control results of urine dip-slide devices.
AB  - Urinary tract infections are frequently diagnosed by using urine dip-slide
      devices, especially in medical practices and small laboratories. We performed a
      retrospective analysis of more than 3000 results obtained by several urine dip
      slide devices during external quality control surveys. We found that an
      underestimation of bacterial counts and a difficulty in identifying mixed flora
      were relatively more frequent in medical practices than in specialized
      laboratories, and that regular participation in external quality control surveys
      correlates with better performances.

PMID- 17020796
TI  - Multiplex detection of Enterocytozoon bieneusi and Encephalitozoon spp. in fecal
      samples using real-time PCR.
AB  - A multiplex real-time polymerase chain reaction (PCR) method was developed for
      the simultaneous detection of Enterocytozoon bieneusi (n = 30) and
      Encephalitozoon spp. (n = 3) in stool samples. The multiplex PCR also included an
      internal control to detect inhibition of the amplification by fecal constituents
      in the sample. The assay was performed on species-specific DNA controls (n = 22)
      and a range of well-defined stool samples (n = 140), and it achieved 100%
      specificity and sensitivity. The use of this assay in a diagnostic laboratory
      offers the possibility of introducing DNA detection as a feasible technique in
      the routine diagnosis of intestinal microsporidian infections.

PMID- 17020797
TI  - Determination of Escherichia coli O types by allele-specific polymerase chain
      reaction: application to the O types involved in human septicemia.
AB  - Escherichia coli can be serotyped by determination of somatic (O), capsular (K),
      and flagellar (H) antigens, and clear associations exist between specific O
      antigens and pathogenic behavior. However, E. coli is very challenging to O type
      with traditional serologic methods, making new methods for E. coli somatic
      antigen detection highly desirable. Here, we describe a simple alternative
      molecular method for determination of the E. coli O type based on allele-specific
      polymerase chain reaction amplification of the 5' portion of the rfb locus. We
      present our application of this new method to the detection of the 12 principal O
      types (O1, O2, O4, O6, O7, O12, O15, O16, O18, O25, O75, and O157) found among
      bloodstream isolates of E. coli. This method allowed us to determine the O types
      of 153 strains previously typed using reference methods with an accuracy
      exceeding 90%. Moreover, some rough or nonagglutinating strains can be
      successfully typed.

PMID- 17020798
TI  - Emergence of serine carbapenemases (KPC and SME) among clinical strains of
      Enterobacteriaceae isolated in the United States Medical Centers: report from the
      MYSTIC Program (1999-2005).
AB  - Among 8885 Enterobacteriaceae tested in the 1999 to 2005 period as part of the
      USA Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program,
      51 strains with increased imipenem and meropenem MIC values (> or =2 microg/mL)
      were detected. bla(KPC) was identified from 28 Klebsiella pneumoniae from 3
      medical centers in the New York City area (8 ribotypes), 2 Klebsiella oxytoca
      from Arkansas (same ribotype), 7 Citrobacter freundii (6 from New York [5
      ribotypes] and 1 from Delaware), 4 Enterobacter spp. from New York (2 species,
      different ribotypes), 3 Escherichia coli (2 from New York and 1 from Ohio, same
      ribotype), and 1 Serratia marcescens (New York). Sequencing confirmed KPC-2 or -3
      in all of the strains. S. marcescens strains harboring SME-1 (2 isolates, same
      ribotype) and SME-2 (1 isolate) were identified from medical centers in Illinois
      and Washington state, respectively. Our results indicate that bla(KPC-2/3) has
      emerged widely (New York City area, Arkansas, Delaware, and Ohio) among
      Enterobacteriaceae isolated in the MYSTIC Program participant sites (2000-2005)
      and continues to be isolated from multiple species, as a result of clonal
      expansion and horizontal gene transfer. The escalating occurrence (0.35%) of
      serine carbapenemases could compromise the role of carbapenems and other beta
      lactams in USA clinical practice although observed in only a few locations to
      date.

PMID- 17020799
TI  - Detection and differentiation between pathogenic and saprophytic Leptospira spp.
      by multiplex polymerase chain reaction.
AB  - A multiplex polymerase chain reaction (PCR) was developed for diagnosing
      leptospirosis and differentiating pathogenic and saprophytic leptospires.
      Specific primers were designed to amplify 23S rDNA from pathogenic Leptospira and
      saprophytic Leptospira spp. PCR products from 27 pathogenic and 5 (including 1
      intermediate) saprophytic serovars were 615 and 316 base pairs (bp),
      respectively. After the restriction enzyme's digestion of PCR products, the
      fragments by SacI of pathogenic serovars and by PstI of saprophytic serovars were
      339 and 276 bp and 202 and 114 bp, respectively. The PCR primers enabled
      amplification of DNA from L. meyeri serovar Ranarum as a pathogenic Leptospira
      spp. The PCR assay could detect 1 to 2 cells of leptospires and not amplify DNA
      from other 18 bacterial species. The sensitivity and specificity of this PCR in
      rat kidney, using isolation as gold standard, were 98.6% and 100%, respectively.
      The most appropriate sample preparation of blood for detecting DNA was buffy
      coat. Among the sample preparations from 7 laboratory-confirmed leptospirosis
      cases, leptospiral DNA was detected in all 7 buffy coat preparations, whereas
      leptospiral DNA was detected in only 3 plasma or serum samples. The PCR assay may
      be useful as a diagnostic tool for leptospirosis.

PMID- 17020800
TI  - An association between anatomic site of Candida colonization and risk of invasive
      candidiasis exists also in preterm neonates in neonatal intensive care unit.

PMID- 17020801
TI  - Prospective randomized study evaluating an absorbable cyanoacrylate for use in
      vascular reconstructions.
AB  - BACKGROUND: An easy-to-use vascular sealant with good safety and efficacy is
      needed to prevent anastomotic bleeding in vascular surgery. This study evaluated
      the safety and efficacy of cyanoacrylate surgical sealant in establishing
      hemostasis of expanded polytetrafluoroethylene to arterial vascular anastomoses
      in arteriovenous (AV) grafts and femoral bypass grafts. METHODS: This
      multicenter, randomized, controlled, open-label study was conducted in a hospital
      setting at 12 sites: 10 in the United States and 2 in Europe. A total of 151
      patients undergoing femoral bypass procedures or AV shunt procedures for
      hemodialysis access using expanded polytetrafluoroethylene grafts were randomized
      2:1 to receive cyanoacrylate surgical sealant or the control (oxidized cellulose)
      between April 26, 2004, and January 18, 2005. Randomization was stratified by
      clinical site and type of procedure. After the anastomosis, cyanoacrylate
      surgical sealant or the control was applied to all anastomosis sites for patients
      undergoing femoral bypass procedures and to only the arterial anastomosis sites
      for patients undergoing AV shunt procedures. The primary end point was the
      elapsed time from clamp release to hemostasis. Secondary end points were the
      proportion of patients achieving hemostasis at t = 0 (immediate), 1, 5, or 10
      minutes after clamp release, use of additional adjunctive measures to achieve
      hemostasis, and occurrence of adverse events. RESULTS: Baseline demographics and
      clinical characteristics showed that the two treatment groups were similar at
      baseline. The mean time from clamp release to hemostasis was 119.3 seconds with
      cyanoacrylate surgical sealant vs 403.8 seconds with the control (P < .001).
      Immediate hemostasis was achieved in 54.5% of patients receiving cyanoacrylate
      surgical sealant and in 10% of those receiving the control. The proportion of
      patients requiring additional adjunctive measures was lower with cyanoacrylate
      surgical sealant, and the occurrence of adverse events was similar in both
      groups. CONCLUSIONS: This study demonstrates that cyanoacrylate surgical sealant
      is effective at reducing the time to hemostasis and achieving immediate
      hemostasis in AV shunt and femoral bypass procedures and that it is safe for
      internal use. Cyanoacrylate surgical sealant is an easy-to-use vascular sealant
      with good safety and efficacy that significantly decreases anastomotic bleeding
      in vascular surgery.

PMID- 17020802
TI  - Bruton's tyrosine kinase together with PI 3-kinase are part of Toll-like receptor
      2 multiprotein complex and mediate LTA induced Toll-like receptor 2 responses in
      macrophages.
AB  - Lipoteichoic acid (LTA) of Gram-positive bacteria initiates innate immune
      responses via Toll-like receptor-2 (TLR2), resulting in the activation of
      intracellular signaling and production of inflammatory cytokines in macrophages.
      Although Bruton's tyrosine kinase (Btk) is biologically important molecule
      implicated in immune regulation and recently in TLR signaling its importance for
      LTA-TLR2 mediated responses has not been evaluated. In this study, we detected
      Btk in the LTA signaling complex with TLR2 and PI 3-kinase (PI3K). The
      constitutive interaction of these proteins was mediated via PI3K Src homology
      (SH3) -domain. Both Btk and PI3K were activated by LTA stimulation and the LTA
      induced cytokine expression was differentially modulated by these kinases. LTA
      induced the activation of nuclear factor kappaB (NFkappaB), however, only Btk
      inhibition affected the LTA induced Ser536 phosphorylation and DNA-binding of
      NFkappaB. In conclusion, our results demonstrate that Btk and PI3K occupy
      important roles in TLR2-induced activation of macrophages, resulting in selective
      regulation of cytokines.

PMID- 17020803
TI  - Prevalence and correlates of adequate performance on a measure of abilities
      related to decisional capacity: differences among three standards for the MacCAT
      CR in patients with schizophrenia.
AB  - Despite the availability of structured decision-making capacity assessment tools,
      insufficient guidance exists for applying their results. Investigators often use
      cutpoints on these instruments to identify potential subjects in need of further
      assessment or education. Yet, information is lacking regarding the effects of
      different cutpoints on the proportion and characteristics of individuals
      categorized as possessing adequate or impaired decisional abilities for consent
      to research. To demonstrate the potential impact of different standards, we
      informed 91 individuals, aged 50 or older with a diagnosis of schizophrenia or
      schizoaffective disorder, about a hypothetical clinical trial, and assessed their
      decisional abilities with the MacArthur Competence Assessment Tool for Clinical
      Research (MacCAT-CR). Three published MacCAT-CR-based standards were applied to
      participants' scores to examine the rates and correlates of categorical
      determinations of adequate performance. The three standards ranged in stringency:
      the most stringent incorporated cutpoints on all three of the major MacCAT-CR
      subscales (Understanding, Appreciation, and Reasoning); the other two standards
      required threshold performance only on the Understanding subscale. The most
      stringent standard resulted in a 57% rate of impaired performance; the
      intermediate standard, 19%; and the least stringent standard, 8%. Nearly half of
      the participants (n=45) were classified as having performed adequately by the
      least stringent standard yet inadequately by the most stringent. The majority of
      these 45 were impaired on the Appreciation subscale (n=9), Reasoning (n=15), or
      both (n=18). Cognitive functioning was correlated with performance status for the
      more stringent standards. These findings underscore the need for refinement of
      capacity assessment procedures and for improvements in the use of capacity
      assessment tools for screening purposes and to assist in categorical capacity
      determinations.

PMID- 17020805
TI  - Genetic diversity in the mycoparasite Sphaerellopsis filum inferred from AFLP
      analysis and ITS-5.8S sequences.
AB  - Genetic diversity among 51 isolates of the mycoparasite Sphaerellopsis filum from
      Melampsora rusts on willow and poplar was examined using AFLP. Genetic variation
      was relatively low among the isolates (Nei & Li's similarities > or =90). Genetic
      diversity calculated using Shannon index was 0.119 at Loughgall, Northern
      Ireland, 0.109 at Markington, northern England, 0.039 at Craibstone, Scotland,
      and 0.015 at Long Ashton, southwest England. At Long Ashton, 14 out of 16
      isolates shared the same AFLP bands. Two genotypes were found at both Markington
      and Loughgall. The low genetic diversity and a high rate of clonality suggested
      that asexual reproduction plays a major role in S. filum epidemics. Sequence
      information was also obtained from the ITS-5.8S region of the ribosomal DNA from
      the S. filum isolates derived from willow and poplar rusts and six isolates
      derived from other sources. ITS sequences were identical among all the 51
      isolates from willow and poplar rusts. ITS analysis placed S. filum isolates from
      Melampsora spp. on willow and poplar, Puccinia coronata on grass and Melampsora
      sp. on Euphorbia sp. into one clade and the isolates from blackberry rust
      Phragmidium violaceum and larch rust Triphragmiopsis laricinum into another.
      Nucleotide sequence differences between the two groups were 8.4-10.4 %. The ITS
      5.8S sequences obtained in this study were compared with those deposited in the
      GenBank database.

PMID- 17020804
TI  - Brain lactate responses during visual stimulation in fasting and hyperglycemic
      subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased
      lactate during neural activation support a broader role for lactate in brain
      energy metabolism than was traditionally recognized. Proton MRS measures of brain
      lactate responses have been used to study regional brain metabolism in clinical
      populations. This study examined whether variations in blood glucose influence
      the lactate response to visual stimulation in the visual cortex. Six subjects
      were scanned twice, receiving either saline or 21% glucose intravenously. Using
      (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was
      visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased
      significantly from resting to visual stimulation. Hyperglycemia had no effect on
      this increase. The order of the slice-selective gradients for defining the
      spectroscopy voxel had a pronounced effect on the extent of contamination by
      signal originating outside the voxel. The results of this preliminary study
      demonstrate a method for observing a consistent activity-stimulated increase in
      brain lactate at 1.5 T and show that variations in blood glucose across the
      normal range have little effect on this response.

PMID- 17020806
TI  - RNA polymerase II gene (RPB2) encoding the second largest protein subunit in
      Phaeosphaeria nodorum and P. avenaria.
AB  - A 5586 bp sequence (accession no. DQ278491), which includes the RNA polymerase II
      gene (RPB2) encoding the second largest protein subunit (RPB2), was obtained from
      the wheat biotype Phaeosphaeria nodorum (PN-w) by PCR amplification. The 3841 bp
      full length RPB2 gene contains two exons and a 52 bp intron, and encodes a
      complete 1262 amino acid protein. Similar to the C-terminals of the beta subunits
      of prokaryotes and yeast RNA polymerases, the deduced RPB2 protein contained many
      structural features needed for gene transcription. Based on the phylogenetic
      analysis with the deduced RPB2 polypeptide sequences, the PN-w was closely
      related to the maize pathogen Cochliobolus heterostrophus. Size differences were
      found in the full length RPB2 gene of cereal Phaeosphaeria species, mainly due to
      differences in intron size. No nucleotide substitutions were found in homothallic
      P. avenaria f.sp. triticea (Pat1) and barley biotype P. nodorum (PN-b) isolates
      used in this study. The nucleotide and deduced amino acid sequences of the RPB2
      gene in Pat1 were closely related to that in PN-w.

PMID- 17020807
TI  - Cortical representation of taste-modifying action of miracle fruit in humans.
AB  - Red berries of a tropical plant called miracle fruit, Richadella dulcifica,
      reduce the sour and aversive taste of acids and add sweet and palatable taste. To
      elucidate the brain mechanism of this unique action of miracle fruit, we recorded
      taste-elicited magnetic fields of the human cerebral cortex. The initial taste
      responses were localized in the fronto-parietal opercular/insular cortex reported
      as the primary taste area. The mean latency of the response to citric acid after
      chewing miracle fruit was essentially the same as that for sucrose and was 250
      300 ms longer than that for citric acid. Since it is known that stimulation with
      acids after the action of miracle fruit induces both sweetness and sourness
      responses in the primate taste nerves, the present results suggest that the
      sourness component of citric acid is greatly diminished at the level of
      subcortical relays, and mostly sweetness information reaches the cortical primary
      taste area. We propose the idea that the qualitative aspect of taste is processed
      in the primary taste area and the affective aspect is represented by the pattern
      of activation among the different cortical areas.

PMID- 17020808
TI  - Imatinib mesylate (Gleevec) protects against streptozotocin-induced diabetes and
      islet cell death in vitro.
AB  - The tyrosine kinase inhibitor imatinib mesylate (Gleevec) has been demonstrated
      to protect various cell types from death by inhibition of Abelson tyrosine kinase
      (c-Abl). The aim of the present study was to establish whether imatinib protects
      the insulin producing beta-cell from the different apoptosis promoting agents in
      vitro and whether imatinib counteracts streptozotocin-induced diabetes in NMRI
      mice. We observe that imatinib attenuated the actions of several different death
      promoting substances. In addition, mice injected with streptozotocin did not
      develop diabetes when given imatinib. The beneficial effects of imatinib may be
      related to inhibition of the pro-apoptotic MAP kinase JNK. We conclude that
      imatinib protects against beta-cell death and that this may contribute to the
      previously reported anti-diabetic actions of imatinib.

PMID- 17020809
TI  - Angiogenic potential difference between two types of endothelial progenitor cells
      from human umbilical cord blood.
AB  - The hierarchy of endothelial progenitor cells (EPCs) in human umbilical cord
      blood has been disclosed. In this study we compare, for the first time, the
      angiogenic potential difference between two types of EPCs. We cultured
      mononuclear cells (MNCs) isolated from human umbilical cord blood using
      endothelial cell-conditioned medium and obtained two types of EPCs, referred to
      as circulating angiogenic cells (CACs) and high proliferative potential
      endothelial progenitor cells (HPP-EPCs). Both types of cells possess
      characteristics of EPCs, including expressing CD31, VE-cadherin, KDR and von
      Willebrand factor, uptake of Ac-LDL and binding to lectin. However, unlike CACs,
      which express CD14 but not CD133, HPP-EPCs express CD133 but not CD14. Also,
      unlike CACs, HPP-EPCs display stronger proliferation and clonogenic potential in
      vitro and show stronger ability to promote vascular growth in the hind-limb model
      of ischemia in mice (BALB/C-nu) in vivo.

PMID- 17020810
TI  - Seasonal variations in the intermediate metabolism of Aegla platensis (Crustacea,
      Aeglidae).
AB  - This study investigated the effects of circadian and seasonal fluctuations on the
      intermediate metabolism of the freshwater crustacean Aegla platensis. Individuals
      were collected each month, at 6:00 h, 12:00 h and 18:00 h, between August 1999
      and June 2002 in the Municipality of Taquara, Rio Grande do Sul, Brazil (29
      degrees 30'0.2''S and 50 degrees 46'50''W). Anomuran crabs were separated by sex,
      and samples of haemolymph, hepatopancreas, abdominal muscle, and gills were
      collected for quantification of glucose, proteins, lipids, triglycerides, and
      glycogen. No variations were observed in the analyzed metabolic parameters for
      the different tissues during the different times of day, either for males or
      females. However, the storage and use of the energetic substrates analyzed did
      fluctuate seasonally. These results suggest an increase in energy demand,
      possibly for the production of gametes during summer, incubation and egg laying
      during autumn and winter, and parental care during spring and summer,
      respectively. A similar pattern has been observed for other crustaceans.

PMID- 17020811
TI  - Cloning and characterization of alpha-amylase from Atlantic salmon (Salmo salar
      L.).
AB  - Amylase has a lower activity in carnivorous fish species, particularly in
      Atlantic salmon. We report the first cloning of a salmonid alpha-amylase cDNA
      from Atlantic salmon, a major species in aquaculture. By amino acid alignment of
      several species, we identified a seven amino acid deletion in one of the large
      loops of the enzyme in relatively close proximity to the active site, that could
      impair substrate binding. We also found the signal peptide to be less hydrophobic
      compared to other species. This may affect import into ER during protein
      synthesis. Active site residues were shown to be conserved. Amylase mRNA
      expression was shown in pancreatic tissue, liver, and in the heart. Using blocked
      p-nitrophenyl-maltoheptaoside as a substrate, we measured a low amylase activity
      in Atlantic salmon intestinal content, which was about half of the activity
      measured in Atlantic cod, whereas activity measured in rainbow trout was fourteen
      times higher. Amylase activities in all three species showed similar degree of
      reduction in hydrolytic activity in a dose-response trial with a wheat amylase
      inhibitor preparation. This indicates similar specific activity per amylase
      molecule.

PMID- 17020812
TI  - CvL, a lectin from the marine sponge Cliona varians: Isolation, characterization
      and its effects on pathogenic bacteria and Leishmania promastigotes.
AB  - CvL, a lectin from the marine sponge Cliona varians was purified by acetone
      fractionation followed by Sepharose CL 4B affinity chromatography. CvL
      agglutinated papainized treated human erythrocytes with preference for type A
      erythrocytes. The lectin was strongly inhibited by monosaccharide d-galactose and
      disaccharide sucrose. CvL is a tetrameric glycoprotein of 28 kDa subunits linked
      by disulphide bridges with a molecular mass of 106 kDa by SDS-PAGE and 114 kDa by
      Sephacryl S300 gel filtration. The lectin was Ca2+ dependent, stable up to 60
      degrees C for 60 min, with optimum pH of 7.5. CvL displays a cytotoxic effect on
      gram positive bacteria, such as Bacillus subtilis and Staphylococcus aureus.
      However, CvL did not affect gram negative bacteria, such as Escherichia coli and
      Pseudomonas aeruginosa. Leishmania chagasi promastigotes were agglutinated by CvL
      up to 2(8) titer. These findings are indicative of the physiological defense
      roles of CvL and its possible use in the antibiosis of bacteria and protozoa
      pathogenic.

PMID- 17020813
TI  - Intermediate metabolism during the ontogenetic development of Anastrepha
      fraterculus (Diptera: Tephritidae).
AB  - The fruit fly Anastrepha fraterculus is a major pest of native and exotic fruit
      trees in South America. Changes in weight, water content and metabolism were
      observed during its ontogenetic development in standard conditions (25 degrees C,
      RH=60% and 14 h:10 h photoperiod). The metabolic variables glycogen, total
      proteins, triglycerides and total lipids were measured by means of
      spectrophotometric methods. The results were correlated with pupae metamorphosis,
      temporal pattern, and beginning of adult life. Pupae were observed daily, and a
      sub-sample of 10 individuals was collected and maintained at -20 degrees C. The
      same procedure was performed with adults at 4 days after adult eclosion. Levels
      of total lipids and triglycerides were constant during pupal development, peaking
      in 312-h-old pupae. In 0-h-old pupae, glycogen levels were high, and decreased
      progressively until the insects were 312 h old. The peak in total proteins
      coincides with the post-histolysis period of the larval tissue (96-120 h). These
      results indicated that glycogen and proteins may be the principal sources of
      energy for metamorphosis. Total lipid and triglyceride contents remained steady
      during metamorphosis, and these were consumed in the first 4 days of adult life.

PMID- 17020814
TI  - Oxygen consumption and thermoregulatory responses in three species of South
      American marsupials.
AB  - Oxygen consumption (VO(2)), body temperature (T(b)) and wet thermal conductance
      (C(wet)), under resting conditions, exposure to low ambient temperature (T(a))
      and during sustained exercise (treadmill running) were measured in three
      phylogenetic related (same family; Didelphidae) South American marsupials
      possessing similar body masses: Caluromys philander (arboreal/fruit and insect
      eating), Philander opossum (terrestrial and arboreal/omnivore), and Metachirus
      nudicaudatus (terrestrial/omnivore). Our measurements of VO(2) and C(wet) under
      resting conditions agree with those previously reported for other marsupials. We
      expected that C. philander would show a lower maximal sustained VO(2), compared
      to the other two species, based on its more reduced skeletal muscle mass.
      However, the values obtained for C. philander were not statistically different
      (ANOVA) from those obtained for the other two species. When exposed to low
      ambient temperature (12 degrees C), differences among the three species were
      detected, i.e., M. nudicaudatus did not survive, while the other two species were
      able to reduce their T(b) under such conditions. C. philander gradually decreases
      its T(b) when cold exposed, and P. opossum shows a more pronounced T(b) drop only
      when exposure to low ambient temperatures occurs for a more prolonged period of
      time.

PMID- 17020815
TI  - Body fluid volume regulation in elasmobranch fish.
AB  - This review addresses an often overlooked aspect of elasmobranch osmoregulation,
      i.e., control of body fluid volume. More specifically the review addresses the
      impact of changes in blood volume in elasmobranchs exposed to different
      environmental salinities. Measurement of blood volume in the European lesser
      spotted dogfish, Scyliorhinus canicula, following acute and chronic exposure to
      80% and 120% seawater (SW) is reported. In 80%, 100% and 120% SW-adapted S.
      canicula, blood volume was 6.3+/-0.2, 5.6+/-0.2 and 4.6+/-0.2 mL 100 g(-1) body
      mass, respectively. Blood volume was significantly higher and lower in 80% and
      120% SW-acclimated animals compared to 100% SW controls. Comparisons are made
      between these results and previously published data. The role of drinking and
      volume regulation in elasmobranchs is discussed. For the first time measured
      water reabsorption rates and solute flux rates across the elasmobranch intestinal
      epithelia are presented. Water reabsorption rates did not differ between 100% SW
      adapted bamboo shark, Chiloscyllium plagiosum, and fish acutely transferred to
      140% SW. For the most part net solute flux rates and direction for both the 100%
      and 140% SW groups were the same with the exception of a net efflux of chloride
      and potassium in the 140% group and influx of these ions in the 100% adapted
      group. The significance of the intestine as part of the overall elasmobranch
      osmoregulatory strategy is discussed as is the role of the kidneys, rectal gland
      and gills in the regulation of body fluid volume in this class of vertebrates.

PMID- 17020816
TI  - Molecular cloning and characterization of Mn-superoxide dismutase from disk
      abalone (Haliotis discus discus).
AB  - The mitochondrial enzyme manganese superoxide dismutase (mitMn-SOD) is one of the
      antioxidant enzymes involved in cellular defense against oxidative stress and
      catalyzes the conversion of O(2)(-) into the stabler H(2)O(2). In this study, a
      putative gene encoding Mn-SOD from disk abalone (Haliotis discus discus, aMn-SOD)
      was cloned, sequenced, expressed in Escherichia coli K12(TB1) and the protein was
      purified using pMAL protein purification system. Sequencing resulted ORF of 681
      bp, which corresponded to 226 amino acids. The protein was expressed in soluble
      form with molecular weight of 68 kDa including maltose binding protein and pI
      value of 6.5. The fusion protein had 2781 U/mg activity. The optimum temperature
      of the enzyme was 37 degrees C and it was active in a range of acidic pH (from
      3.5 to 6.5). The enzyme activity was reduced to 50% at 50 degrees C and
      completely heat inactivated at 80 degrees C. The alignment of aMn-SOD amino acid
      sequence with Mn-SODs available in NCBI revealed that the enzyme is conserved
      among animals with higher than 30% identity. In comparison with human mitMn-SOD,
      all manganese-binding sites are also conserved in aMn-SOD (H28, H100, D185 and
      H189). aMn-SOD amino acid sequence was closer to that of Biomphalaria glabrata in
      phylogenetic analysis.

PMID- 17020817
TI  - Phospholipid-hydroperoxide glutathione peroxidase (GPx-4) localization in resting
      platelets, and compartmental change during platelet activation.
AB  - Seleno-glutathione peroxidases are an important family of antioxidant enzymes,
      that include the phospholipid hydroperoxide glutathione peroxidase (GPx-4), an
      enzyme that reduces lipid hydroperoxides in membranes. The essential
      characteristics of platelet GPx-4 were found to be the same as the GPx-4 from
      other tissues. To explore the subcellular expression of GPx-4 in human platelets,
      we first investigated both its activity and localization in subcellular
      fractions. About 47% of the total cell enzyme activity was found in the membrane
      fractions, 29% in the mitochondria and 23% in the cytosol fractions. The same
      subcellular distribution of GPx-4 protein was demonstrated in resting platelets.
      This distribution data was further established by confocal microscopy. Of major
      potential biological significance, this distribution changed when platelets were
      activated. Confocal immunofluorescence microscopy localized mainly GPx-4 to
      membranes in contrast to cytoplasm in the resting cells. Based on these results
      we propose that cytoplasmic GPx-4 could be moved to the membrane for protection
      during platelet activation. This enzyme would then be important to maintain the
      integrity of platelet function in vascular system stressed by oxidative
      reactions.

PMID- 17020818
TI  - Lack of association between FCRL3 and FcgammaRII polymorphisms in Japanese type 1
      autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized
      by chronic inflammation of the liver. Although the HLA-DRB1*0405 allele is
      associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains
      undefined. Recently, polymorphisms of Fcgamma receptors (FcgammaR) and Fc
      receptor-like gene 3 (FCRL3) were linked to a variety of autoimmune diseases, and
      may be at least partially responsible for susceptibility to AIH. In this study,
      we genotyped FcgammaRIIA, FcgammaRIIB, and four FCRL3 polymorphisms in 87
      Japanese patients with type 1 AIH and 97 ethnically matched controls using the
      TaqMan assay. Although we were able to detect significantly lower serum IgG
      concentrations in AIH patients specifically with the FCRL3-110A/A genotype, we
      observed no difference in the distribution of the genotypes between patients and
      controls, implying that susceptibility to type 1 AIH in Japanese patients is not
      influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms.

PMID- 17020819
TI  - Enzymatic antioxidant response of a labrid fish (Coris julis) liver to
      environmental caulerpenyne.
AB  - Exposure of marine animals to certain toxic compounds can enhance reactive oxygen
      species production with subsequent damage to macromolecules and alterations in
      oxidant defenses levels. Caulerpenyne is the major metabolite synthesized by
      Caulerpa species, used as chemical defense affecting several cellular and
      molecular targets. We assessed the changes produced by the presence of Caulerpa
      spp. in the activities of antioxidant enzymes as well as lipid peroxidation
      levels in liver of the teleost Coris julis. Fish were captured at two stations
      with Caulerpa species-Caulerpa taxifolia and Caulerpa prolifera-and at a region
      with the seagrass Posidonia oceanica as negative control. Caulerpenyne
      concentration was significantly higher in C. prolifera than in C. taxifolia
      (p<0.05). Glutathione S-transferase, glutathione peroxidase and glutathione
      reductase activities were significantly higher in both Caulerpa stations compared
      to the P. oceanica (p<0.05). No statistical difference (p>0.05) existed in
      catalase activity between groups. Glutathione reductase activity is significantly
      higher in C. prolifera station than in C. taxifolia (p<0.05). Despite the
      variations in the antioxidant enzyme activities, there was no significant
      difference in malondialdehyde concentration. In conclusion, the production of
      caulerpenyne by Caulerpa species could induce an antioxidant adaptation in the
      liver of C. julis in order to prevent oxidative damage.

PMID- 17020821
TI  - Metal accumulation and enzyme activities in gills and digestive gland of pearl
      oyster (Pinctada fucata) exposed to copper.
AB  - The effects of exposure to copper under laboratory-controlled conditions were
      investigated in the pearl oyster, Pinctada fucata. Metal accumulation and the
      activity of five enzymes were measured: two immune defense involved enzymes [acid
      phosphatase (AcPase) and phenoloxidase (PO)], two antioxidant enzymes [superoxide
      dismutase (SOD) and Se-dependent glutathione peroxidase (Se-GPx)] and one metal
      sensitive enzyme [alkaline phosphatase (ALP)]. Analyses were carried out in gills
      and digestive gland of oysters exposed to 0.05 microM and 0.5 microM copper,
      respectively, at 12, 24, 48 and 72 h of exposure. The digestive gland of P.
      fucata was the main copper accumulation organ when oysters were exposed to low
      concentrations, whereas gills became the target organ in oysters exposed to high
      concentrations. The adaptation and recovery of the oysters were observed in our
      study. Levels of the copper accumulation and the sensitivity to copper were the
      main, if not, part of the reasons for the various responses of the selected
      enzymes. Se-GPx may potentially be used as biomarkers in biotesting of marine
      heavy metal pollutions. The enzymatic responses were compared with those of other
      studies and the possible reasons were discussed.

PMID- 17020820
TI  - The zebrafish (Danio rerio) embryo as a model system for identification and
      characterization of developmental toxins from marine and freshwater microalgae.
AB  - The zebrafish (Danio rerio) embryo has emerged as an important model of
      vertebrate development. As such, this model system is finding utility in the
      investigation of toxic agents that inhibit, or otherwise interfere with,
      developmental processes (i.e. developmental toxins), including compounds that
      have potential relevance to both human and environmental health, as well as
      biomedicine. Recently, this system has been applied increasingly to the study of
      microbial toxins, and more specifically, as an aquatic animal model, has been
      employed to investigate toxins from marine and freshwater microalgae, including
      those classified among the so-called "harmful algal blooms" (HABs). We have
      developed this system for identification and characterization of toxins from
      cyanobacteria (i.e. "blue-green algae") isolated from the Florida Everglades and
      other freshwater sources in South and Central Florida. Here we review the use of
      this system as it has been applied generally to the investigation of toxins from
      marine and freshwater microalgae, and illustrate this utility as we have applied
      it to the detection, bioassay-guided fractionation and subsequent
      characterization of developmental toxins from freshwater cyanobacteria.

PMID- 17020822
TI  - For comparison: experience with a children's obesity camp.
AB  - BACKGROUND: The alarming rise in childhood obesity has resulted in a number of
      bariatric surgical initiatives. To interpret the outcomes, a comparison with a
      nonoperative approach is prudent. METHODS: In 2003, 2004, and 2005, we measured
      the outcomes produced by an isolated summer camp in North Carolina for 74, 99,
      and 89 obese children and adolescents with a mean age of 12.7 +/- 2.3, 13.0 +/-
      1.9, and 13.2 +/- 1.8 years and initial body mass index (BMI) of 33.1 +/- 5.7,
      33.4 +/- 6.4, and 32.9 +/- 7.0 kg/m2, respectively. The camp featured a 1700/d
      caloric diet, daily aerobic and resistance weight training exercise, nutrition
      classes, and weekly sessions with a psychologist. The changes in weight, BMI,
      body shape measurements, and fitness level were assessed. The average length of
      stay was 4.3, 4.2, and 4.4 weeks, respectively, in 2003, 2004, and 2005. RESULTS:
      The BMI, body shape, and weight change measures significantly improved during
      each of the summers. The campers lost 1.6, 2.0, and 1.8 kg/wk during each of the
      3 years. Their waist measurements decreased by 9.1 +/- 5.12 cm, 9.9 +/- 5.6 cm,
      and 8.1 +/- 5.8 cm. Significant improvements occurred in the timed sprints, .5
      mile (0.8-km) run, and vertical jump. Of those campers staying for two summers,
      4.4% continued to reduce their BMI despite growth, 56.5% maintained their BMI at
      less than the initial baseline measurement, and 39.1% increased their BMI to
      greater than the baseline. The co-morbidities also improved. One camper, aged 15
      years, weighing 211 kg, progressed from being able to walk 3 steps to managing
      the 100-yard (91-m) dash in 42 seconds after losing 35 kg in 8 weeks. CONCLUSION:
      Diets, exercise, and behavioral modification are useful approaches in severely
      obese children that can, in some, produce significant albeit expensive long-term
      results. Recidivism is a problem. Surgical outcomes must compare favorably with
      these outcomes.

PMID- 17020823
TI  - Endoscopy and upper gastrointestinal contrast studies are complementary in
      evaluation of weight regain after bariatric surgery.
AB  - BACKGROUND: To assess the utility of upper endoscopy (EGD) and upper
      gastrointestinal (UGI) contrast studies in the evaluation of weight regain after
      previous bariatric surgery. METHODS: We retrospectively reviewed the findings of
      EGD and UGI studies for patients referred to our center for weight regain after
      bariatric surgery. All patients received a dietary assessment concomitant with
      the anatomic evaluations. RESULTS: From January 2003 and March 2006, 30 patients
      qualified for the study (25 women and 5 men, average age 49 years). Of the 30
      patients, 16 had undergone gastroplasty and 14 open Roux-en-Y gastric bypass. Of
      the 30 patients, 27 (90%) had > or =1 abnormality detected on UGI study or EGD.
      Of these abnormalities, 10 were gastrogastric fistulas, 8 of which were detected
      with both UGI study and EGD; 11 dilated pouches were diagnosed by EGD but only 2
      were also diagnosed on the UGI study. An enlarged stoma size was diagnosed in 7
      patients (6 by EGD and 1 on the UGI study). Also, the UGI study diagnosed 1 Roux
      limb and 7 esophageal abnormalities not seen on EGD, and EGD diagnosed 4
      esophageal and 3 gastric abnormalities not seen on the UGI study. On the basis of
      these findings and the dietary evaluation, 23 patients (77%) were offered a
      revisional procedure. CONCLUSION: EGD and UGI contrast studies are complementary
      in the evaluation of patients with weight regain after bariatric surgery. The
      combination of the 2 studies detected all the gastrogastric fistulas present. EGD
      provided more useful pouch and stomal information, and the UGI study detected
      esophageal or Roux limb abnormalities that frequently require additional
      evaluation.

PMID- 17020824
TI  - Anastomotic stenosis after Roux-en-Y gastric bypass: A rational approach to
      treatment.
AB  - BACKGROUND: Anastomotic stenosis, a common sequela to Roux-en-Y gastric bypass,
      has a reported incidence of 1.6-27% and recurs in 17-33%. No universal guidelines
      for optimal treatment exist. The aim of this study was to develop guidelines to
      treat stenosis that achieve the lowest rate of recurrence while avoiding the
      complications of excessive dilation. METHODS: This prospective 2-part study
      enlisted consecutive patients undergoing Roux-en-Y gastric bypass who developed
      an anastomotic stenosis. In the first part, all patients, regardless of the grade
      of stenosis, underwent dilation to 12 mm and were followed up for recurrence. In
      the second part, patients underwent dilation according to the grade of stenosis
      (12 mm for low, 13.5 mm for medium, 15 mm for high) and were followed up for
      recurrence. RESULTS: Among 1345 consecutive Roux-en-Y gastric bypass patients,
      204 developed an anastomotic stenosis (15.2%). No differences were found in
      gender, mean age, preoperative body mass index, or weight loss at 1 year. In part
      1, the recurrence rate for low-, medium-, and high-grade stenosis was 2.6%,
      34.4%, and 35.9%. In part 2, the corresponding rates were 9.7%, 26.3%, and 43.6%.
      The corresponding mean number of additional dilations per patient with recurrence
      in part 1 was 1.0, 1.5, and 2.1 and, in part 2, were 1.0, 1.0 and 1.2.
      CONCLUSION: The results of this study have shown that the stenosis grade can
      predict the risk of recurrence and determine the optimal balloon size. Definitive
      treatment was achieved in >90% of patients with low-grade stenosis dilated to 12
      mm. Medium- and high-grade stenosis predicted > or =25% recurrence, but
      increasing the balloon size reduced the number of additional dilations required
      for patients with recurrence.

PMID- 17020826
TI  - Comparison of normal mode analyses on a small globular protein in dihedral angle
      space and Cartesian coordinate space.
AB  - Normal mode analyses on the protein, bovine pancreatic trypsin inhibitor, in
      dihedral angle space and Cartesian coordinate space are compared. In Cartesian
      coordinate space it is found that modes of frequencies lower than 30 cm(-1)
      contribute 80% of the total mean-square fluctuation and are represented almost
      completely by motions in the dihedral angles. Bond angle and length fluctuations
      dominate in modes above 200 cm(-1), but contribute less than 2% to the total mean
      square fluctuation. In the low-frequency modes a good correspondence between
      patterns of atomic displacements was found, but on average the root-mean-square
      fluctuations of the Cartesian coordinate modes are 13% greater than their
      dihedral angle counterparts. The main effect of fluctuations in the bond angles
      and lengths, therefore, is to allow the dihedral angles to become more flexible.
      As the important subspaces determined from the two methods overlap considerably,
      dihedral angle space analysis can be applied to proteins too large for Cartesian
      coordinate space analysis.

PMID- 17020825
TI  - Heterogeneity of protein conformation in solution from the lifetime of tryptophan
      phosphorescence.
AB  - The decay of Trp phosphorescence of proteins in fluid solutions was shown to
      provide a sensitive tool for probing the conformational homogeneity of these
      macromolecules in the millisecond to second time scale. Upon examination of 15
      single Trp emitting proteins multiexponential decays were observed in 12 cases, a
      demonstration that the presence of slowly interconverting conformers in solution
      is more the norm rather than an exception. The amplitude of preexponential terms,
      from which the conformer equilibrium is derived, was found to be a sensitive
      function of solvent composition (buffer, pH, ionic strength and glycerol
      cosolvent), temperature, and complex formation with substrates and cofactors. In
      many cases, raising the temperature, a point is reached at which the decay
      becomes practically monoexponential, meaning that conformer interconversion rates
      have become commensurate with the triplet lifetime. Estimation of activation free
      energy barriers to interconversion shows that the large values of DeltaG* are
      rather similar among polypeptides and that the protein substates involved are
      sufficiently long-lived to display individual binding/catalytic properties.

PMID- 17020827
TI  - Analysis of biochemical reactions in equilibrium: hydrolysis of penicillin and
      ampicillin.
AB  - A general equilibrium model for a class of biochemical reactions was formulated,
      using the formalism of binding polynomials for the evaluations of the various
      species. Thermodynamic equilibrium constant was obtained from the observed
      equilibrium total concentrations of reactants at specified pH and certain ligand
      concentrations. Results for the hydrolysis of penicillin and ampicillin were
      analyzed with this equilibrium model. Predicted fractions of hydrolysis products
      at various pH values were calculated.

PMID- 17020828
TI  - Spatial phase pattern in one-dimensional arrays of limit cycle oscillators with
      discrete coupling.
AB  - We present a model of limit cycle oscillators for collective oscillations in
      intracellular calcium concentration in cell communities. A phase-dependent
      discrete coupling between nearest neighbors is introduced into the model on the
      basis of the experimental observation that intercellular transmission of calcium
      or calcium mobilizing messenger is effected by gap junction and gap junctional
      permeability is affected by intracellular calcium concentration. The spatial
      phase pattern of several clusters in which oscillations are in phase is found
      with the phase-dependent discrete coupling.

PMID- 17020829
TI  - An oxygenation-sensitive dye binding to Carcinus maenas hemocyanin.
AB  - The interaction of 4',6-diamidino-2-phenylindole (DAPI) with Carcinus maenas
      hemocyanin has been investigated by steady state fluorescence, dynamic
      fluorescence and circular dichroism measurements. The dye binds to apohemocyanin
      (without copper) as well as to oxygenated hemocyanin and to deoxygenated
      hemocyanin with very similar affinities (kd approximately equal to 1 microM ) and
      number of binding sites (one per subunit). In contrast, the fluorescence quantum
      yield enhancement of DAPI bound to oxygenated hemocyanin is nearly 60% lower than
      that observed for deoxygenated and apo forms. The decrease of fluorescence of the
      dye bound to deoxygenated hemocyanin is a sigmoidal function of the oxygen
      partial pressure, specular to that observed by following the absorbance of the
      copper-oxygen charge transfer band at 340 nm. This result provides preliminary
      evidence that DAPI may be used as a functional probe to monitor the cooperative
      binding of oxygen to the protein. The higher fluorescence quantum yield of DAPI
      bound to either apohemocyanin or deoxygenated protein is characterized by a
      single fluorescence decay with lifetime of about 3 ns, while with the oxygenated
      protein two components of about 1 ns and 3.0 ns are observed. This result is
      interpreted assuming the existence of two rotamers of DAPI in solution (Szabo et
      al. Photochem. Photobiol. 44 (1986) 143-150) both able to interact with
      oxygenated hemocyanin but only one to deoxygenated and apo forms. We conclude
      that the different fluorescence behaviour of the dye induced by the presence of
      oxygen bound to the protein is probably due to a structural change of hemocyanin
      in cooperative interaction with oxygen. Furthermore, the interaction is confirmed
      by the induced negative ellipticity of DAPI bound to apohemocyanin and deoxy
      hemocyanin and by the increase of fluorescence anisotropy of DAPI bound to all
      forms of protein investigated.

PMID- 17020830
TI  - Ionization and binding equilibria of papaverine in ionic micelles studied by 1H
      NMR and optical absorption spectroscopy.
AB  - The binding of the vasodilator drug papaverine (PAV) to micelles of zwitterionic
      N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS), cationic
      cetyltrimethylammonium chloride (CTAC) and anionic sodium dodecylsulfate (SDS) in
      aqueous solution was studied by 1H NMR and electronic absorption spectroscopy. In
      the presence of HPS or CTAC, the apparent pK(a) of PAV decreased by about 2
      units, while it increased by about 2 units upon binding to SDS. However, the
      chemical shift patterns of both protonated (PAVH+) and deprotonated (PAV0) forms
      of PAV are not sensitive to the type of surfactant. The association constants
      were estimated as 5 +/- 2 M(-1) for PAVH+-CTAC, 8 +/- 3 M(-1) for PAVH+-HPS, (7
      +/- 2) x 10(5) M(-1) for PAVH+-SDS, and 1.5 x 10(3) to 3.0 x 10(3) M(-1) for the
      complexes of PAV0 with all three types of micelles. Using these data, an
      electrostatic potential difference on the micelle-water interface was calculated
      as 150 +/- 10 mV for CTAC, 140 +/- 10 mV for HPS and - 140 +/- 10 mV for SDS. The
      results suggest that PAV aromatic rings are located in the hydrophobic part of
      the micelle. The electrostatic attraction or repulsion of the protonated
      quinoline nitrogen and surfactant headgroups changes the affinity of PAV to
      micelles and, thus, shifts the ionization equilibrium of PAV. The electrostatic
      potential of HPS micellar surface is determined by the cationic dimethylammonium
      headgroup fragment, whereas the anionic sulfate fragment attenuates the effective
      charge of HPS headgroup.

PMID- 17020831
TI  - Influence of vesicle curvature on fluorescence relaxation kinetics of
      fluorophores.
AB  - The effect of membrane curvature on the fluorescence decay of 2-p-toluidinyl
      naphthalene-6-sulfonic acid (TNS), 2-(9-anthroyloxy) stearic acid (2-AS) and 12
      (9-anthroyloxy)-stearic acid (12-AS) was investigated for egg lecithin vesicles
      of average diameter dm = 22 nm and 250 nm. The biexponential fluorescence decay
      of TNS at the red edge of the emission spectrum was analysed according to the
      model of Gonzalo and Montoro [1]. Over the entire temperature range (1-40 degrees
      C) the small TNS labelled vesicles showed significantly shorter solvent
      relaxation times tau(r) than their larger counterparts (e.g. 1.3 ns compared with
      2.1 ns at 5 degrees C), indicating a higher mobility of the hydrated headgroups
      in the highly curved, small vesicles. The fluorescence decay of both AS
      derivatives is also biexponential. While the shorter decay times (1-3 ns) are
      practically identical for small and large vesicles, the longer decay times (5-14
      ns) are identical only for 12-AS but not for 2-AS. This indicates that the
      microenvironment is similar in small and large vesicles deep in the membrane in
      spite of the differences in curvature.

PMID- 17020832
TI  - The conformational equilibria of a renin inhibitor peptide in solution.
AB  - The conformational equilibrium of a decapeptide renin inhibitor (Renin Inhibitory
      Peptide (RIP), NH-P-H-P-F-H-F-F-V-Y-K-CO2H) in water, methanol and
      trifluoroethanol has been investigated. The value of a combined spectroscopic
      approach was apparent, with the need to define conformational states that were
      mixtures of conformational forms. Similarities between this study and that of the
      Melanin Concentrating Hormone (MCH) core peptide (5-14) are notable [1]. In
      water, two beta-turn conformations and an extended form were found to be in
      equilibrium, with cis/trans isomerism at Pro-3. Extended conformations associated
      with the P(II) helix and irregular forms were more favoured in aqueous
      environments. In MeOH and TFE, two beta-turn conformations associated with
      overlapping sequences and cis/trans isomerism at Pro-3 amide bond were seen to be
      in equilibrium. 2D ROESY and chemical-exchange cross-peaks were detected by 1H
      NMR and used to build up detailed models of the interconverting beta-turn
      conformations of RIP.

PMID- 17020833
TI  - Extended theoretical analysis of irreversible protein thermal unfolding.
AB  - The theoretical analysis of the protein denaturation model which includes an
      irreversible, exothermic and rate-limited step has been improved and applied to
      the DSC profile of Azurin. The two-step nature of the irreversible denaturation
      of globular proteins is usually depicted in the following simplified scheme: N <-
      > U <--> F, which is known as the Lumry and Eyring model. In most of the works
      concerning the thermal unfolding of proteins, it is usually assumed that the
      irreversible step of the process does not take place significantly during the
      short time the protein spends in the temperature range of the DSC transition, or
      if this is not the case, that this irreversible step occurs with a negligible
      thermal effect. As we will show, this last assumption cannot be accepted
      acritically; in fact we have found that in the case of Azurin an evident
      exothermic effect occurs at the end of the transition. In order to fit the
      experimental Cp(exc) profile of Azurin, we have analyzed a model in which the
      exothermic effects of the irreversible step and the variations of DeltaH with
      temperature are taken into account. Our model was first tested simulating a
      series of profiles and considering the effects of the variation of the parameters
      on the shape of the curves, and successfully used to fit the experimental
      calorimetric profile of Azurin.

PMID- 17020834
TI  - Cercospora beticola toxins. Part VI: preliminary studies of protonation and
      complexation equilibria.
AB  - The biological activity of Cercospora beticola toxins might be enhanced by the
      complex formation with magnesium. Therefore, protonation and complexation
      equilibria of beticolins were studied. Beticolins carry three dissociable
      functions (H3B) two of which dissociate at a physiological pH. In the presence of
      magnesium, the neutralisation and protonation curves provide evidence for the
      formation of complexes. At physiological pH, the uncharged complex, Mg2H2B2, is
      the predominant form. The nonionised forms of free beticolin-1 and -2 fluoresce
      in a 50% dioxan-water solution and their emission maxima shift to higher
      wavelengths in water. The dianion HB(2-) is non-fluorescent both in water and in
      less polar media. The formation of the Mg2H2B2 complex which strongly fluoresces
      in nonpolar media is confirmed by a marked increase in fluorescence at 520 nm and
      by a shift of the excitation maximum.

PMID- 17020835
TI  - Editor's overview.

PMID- 17020836
TI  - Image plate detectors for macromolecular neutron diffractometry.
AB  - Neutron diffraction studies of macromolecules require large position sensitive
      detectors. It is proposed that such a device can be based on image plate
      technology, which relies on re-usable photostimuable phosphors, combined with a
      neutron to gamma-ray converter. Design parameters such as the best wavelength for
      the neutron radiation and the optimum sample to detector distance are discussed,
      and a design for a cylindrical detector is outlined. Presently a prototype of
      such a detector is being built, and the very first test-recording of an X-ray
      diffraction pattern from a protein crystal is presented.

PMID- 17020837
TI  - Detergent organisation in solutions and in crystals of membrane proteins.
AB  - The use of neutron scattering in studying the organisation of detergents in pure
      micelles, in protein/detergent mixed micelles and in crystals of membrane
      proteins, is reviewed. Small angle scattering has been used to study the size,
      shape and composition of pure and mixed protein/detergent micelles as well as the
      effects of adding small amphiphiles. The technique of contrast variation applied
      to single crystals is described and its application to the determination of the
      organization of detergent in single crystals of membrane proteins is discussed. A
      better understanding of protein/detergent interactions should help in producing
      crystals of membrane proteins more easily as well as clues to the nature of
      protein/lipid interactions in vivo.

PMID- 17020838
TI  - The observation of structural transitions of a single protein molecule.
AB  - Coherent neutron scattering measurements of an amorphous, in vivo deuterated C
      phycocyanin are compared with a calculation of the individual protein molecule's
      coherent static structure factor. Both show the significant features associated
      with known structure factors of several amorphous materials, most notably, an
      unusually sharp first diffraction peak occurring near 1.4 A(-1). We show that in
      the protein, such a peak results from the product of a form factor associated
      with correlations of atoms within individual amino acids and a structural term
      expressing inter-amino-acid correlations. The measurement, interpreted through
      behavior of the first diffraction peak, indicates that inter-amino-acid
      correlations - a measure of the protein's medium-range structure - undergo
      transitions which are primarily related to hydration rather than to temperature.

PMID- 17020839
TI  - Small angle neutron scattering, total cross-sections and mass density
      measurements of concentrated NaCl and KCl solutions in H2O or D2O.
AB  - The mass densities, total cold neutron cross sections and small angle scattering
      of concentrated NaCl and KCl solutions in H2O or D2O (2H2O) were measured at 20
      degrees C. The partial specific volumes of both salts increase with salt
      concentration and are significantly smaller in D2O than in H2O, showing that
      these salt solutions cannot be considered as isomorphous in H2O and D2O. As salt
      concentration increases for both salts, the total coherent cross sections for
      neutrons of the solutions also increase while the coherent small angle scattering
      decreases-observations that are consistent, respectively, with increasing
      correlations involving the ion and water components and a decrease in the
      particle number density and/or concentration fluctuations, in the solutions.
      Changes in incoherent scattering with salt concentration are essentially those
      expected from the solution compositions and densities.

PMID- 17020840
TI  - Structure of dodecyl sulfate-protein complexes at subsaturating concentrations of
      free detergent.
AB  - Earlier neutron small-angle scattering experiments had revealed the low
      resolution structure of the complex between sodium dodecyl sulfate (SDS) and the
      single polypeptide (452 amino acid residues) of a water-soluble enzyme. The
      saturated complex consists of three globular micelles which are connected by
      short flexible polypeptide segments. New experiments, described here, were
      performed at subsaturating concentrations of free SDS in equilibrium with the
      complex. The data show a decrease in stoichiometry from one bound dodecyl sulfate
      (DS) anion per two amino acid residues near the critical micelle concentration
      (CMC) to one per four residues at half the CMC. At 0.3 CMC, a two-micelle complex
      is formed by the recombination of the small amino-terminal micelle with the
      middle one; and the center-to-center distance between the carboxyl-terminal
      micelle and the middle one decreases from 7.5 to 6.2 nm. These structural data
      allow us to better understand earlier results obtained with high-performance
      agarose gel chromatography of the same SDS-protein complexes.

PMID- 17020841
TI  - How random is a highly denatured protein?
AB  - There has been renewed interest in determining the physicochemical properties of
      denatured states of proteins. In many denatured states there is evidence for the
      existence of nonrandom configurational distributions. Here we examine the small
      angle neutron scattering profile of yeast phosphoglycerate kinase in the native
      state and in highly denaturing conditions. We show that the denatured protein
      scattering profile can be interpreted using a model developed for synthetic
      polymers in which the chain behaves as a random coil in a good solvent, i.e. with
      excluded volume interactions. The implications of this result for our
      appreciation of the protein folding process are discussed.

PMID- 17020842
TI  - Protein interactions and dynamics probed by quantum chemistry, computer
      simulations and neutron experiments.
AB  - We review some recent experiments and calculations on aspects of the structure
      and dynamics of proteins and related systems. The use of quantum chemical
      techniques to determine geometries and energies of supramolecular complexes of
      biological interest is illustrated, and the concomitant development of empirical
      energy functions for use in protein simulations outlined. We describe how
      simulations of crystalline peptides and amino-acids using an empirical force
      field can be combined with appropriate coherent and incoherent inelastic neutron
      scattering experiments to elucidate the characteristics of lattice vibrations and
      diffusive atomic motions in the crystals. The application of molecular dynamics
      simulations to the interpretation of incoherent neutron scattering experiments on
      proteins is examined and the resulting ideas on the general characteristics of
      protein motion discussed in terms of their functional implications.

PMID- 17020843
TI  - Water dynamics in charged and uncharged polysaccharide gels by quasi-elastic
      neutron scattering.
AB  - Using a microeV neutron spectrometer we have studied the mobility of water in
      gels formed by two polysaccharides: agarose and hyaluronic acid. Agarose is a
      nearly uncharged polysaccharide; its gels are fairly stiff, quasi-random networks
      of fibre bundles. Hyaluronic acid is a highly charged polysaccharide capable of
      retaining large amounts of water in entangled meshworks with unusual rheological
      properties. We have analysed sets of quasi-elastic lineshapes broadened by two
      proton populations with different degrees of freedom. The resulting microscopic
      mobility parameters and their temperature dependence reveal a complex behaviour.
      The overall effect of the biopolymer network is to increase translational as well
      as rotational relaxation times, but the changes observed are not dramatic and
      cannot fully account for the strikingly different macroscopic properties of these
      gels. Local electrostatic interactions (over 3 to 20 A) do not appear to
      influence significantly the rheological behaviour.

PMID- 17020844
TI  - Inelastic neutron-scattering study of the proton transfer dynamics in polyglycine
      I at 20 K.
AB  - Inelastic neutron-scattering (INS) spectra of three isotopic derivatives of
      polyglycine I (-COCH2NH-)n, (-COCD2NH-)n, and (-COCH2ND-)n at 20 K are presented
      from 30 to 4000 cm(-1). The band frequencies are compared to those observed in
      the infrared and Raman. Assignments in terms of group vibrations are proposed.
      These mostly resemble previous assignment schemes, except for the amide bands.
      The INS intensities reveal that the proton dynamics for the (N)H proton are
      totally different from those proposed previously. They are independent of the
      molecular frame and the valence bond approach is not consistent with observation.
      A phenomenological approach is proposed in terms of localized modes. The
      calculated intensities reveal that the (N)H stretching mode has two components at
      approximately 1377 and 1553 cm(-1). This is a dramatic change compared to all
      former assignments at approximately 3280 cm(-1) based on infrared and Raman data.
      These proton-dynamics are associated with a weakening of the NH bond due to the
      ionic character of the hydrogen bond (N(delta-)...H+...O(delta'-)) and proton
      transfer. The infrared and Raman spectra are re-examined and a new assignment
      scheme is proposed for the amide bands; the amide A and B bands are re-assigned
      to the overtones of the stretching modes. A symmetric double-minimum potential
      for the proton is consistent with all the observations.

PMID- 17020845
TI  - Self-association processes involving anthracene labeled phosphatidylcholines in
      model membrane.
AB  - When studying lipid-lipid or lipid-protein interaction in membranes, the correct
      interpretation of data obtained when using fluorescent phospholipid probes
      requires the best possible knowledge of probe behaviour in phospholipid
      membranes. Analysis of the translational dynamics and photochemical properties of
      the anthracene-labeled phosphatidylcholine (EAPC) shows that a self-association
      process occurs with this probe in the membrane at the ground state. This
      anthracene self-association is characterized and leads to a hypochromic effect
      which has been studied by means of ultraviolet absorption spectroscopy in
      unilamellar egg-yolk phosphatidylcholine (EggPC) vesicles. A model with
      indefinite linear self-association, in which each step has the same equilibrium
      constant, best describes the data. The equilibrium constant was found to be in
      the 300-500 M(-1) range and the complex lateral distribution pattern of EAPC in
      model membranes, which results from this self-association process, is
      characterized and seems to be mainly controlled by the amount of EAPC
      incorporated into the lipid bilayer.

PMID- 17020846
TI  - Effect of subzero incubation on fluoride binding by laccase.
AB  - We have refined a useful incubation method for preparing adducts of tree laccase
      with inhibitor anions; however, the technique should have wider application. The
      procedure involves incubating a previously frozen aqueous solution at subzero
      temperature. Factors influencing the amount of adduct that forms include the
      nature of the buffer, pH changes that occur at subzero temperatures and the
      presence of glycerol. In the absence of a glassing agent like glycerol, the phase
      separation and solute pooling that occur with ice formation help drive adduct
      formation. The results reveal several important factors to consider in designing
      or interpreting low-temperature spectroscopic investigations.

PMID- 17020847
TI  - Fit of the dielectric anomaly of squid axon membrane near heat-block temperature
      to the ferroelectric Curie-Weiss law.
AB  - In a 1969 experiment, Palti and Adelman reported that the capacitance of squid
      axon membrane rises sharply with temperature between 40 and 50 degrees C. This
      phenomenon is here explained by the ferroelectric-superionic transition
      hypothesis, which also explains channel gating and other phenomena observed in
      excitable membranes. According to this hypothesis gating in the Na channel is due
      to a first-order phase transition from a ferroelectric (closed) state to a
      superionic (open) state. From it, the dielectric permittivity of the Na channel,
      and hence the temperature-dependent component of membrane capacitance, is
      predicted to obey the ferroelectric Curie-Weiss law near the transition (heat
      block) temperature. The Palti-Adelman data are fitted accurately by the predicted
      relationship. The parameters obtained permit an estimate to be made of the Curie
      constant of the channel, approximately 6400 K, consistent with an order-disorder
      ferroelectric. The Na channel appears to be a ferroelectric polymer component of
      a lyotropic lamellar liquid crystal.

PMID- 17020848
TI  - Bistability and reaction thresholds in the phenol-inhibited peroxidase-catalyzed
      oxidation of indole-3-acetic acid.
AB  - A model mechanism for the phenol-inhibited peroxidase-catalyzed oxidation of
      indole-3-acetic acid (IAA) is proposed and analyzed. The model involves an
      autocatalytic free radical species that sustains IAA oxidation and the phenolic
      inhibitor acting as a free radical scavenger. Under a fixed set of parameter
      values, the model exhibits a coexistence of two stable steady states. This
      bistability phenomenon explains the origin of the experimentally observed
      threshold inhibitor concentrations above which IAA oxidation stops. The variation
      of the inhibitor threshold level with enzyme and substrate concentrations are
      reproduced by the model almost quantitatively.

PMID- 17020849
TI  - Interaction of calcium ion and maleic acid copolymer.
AB  - Interaction between Ca2+ ion and poly(styrene-alt-maleic acid) was studied by
      using a Ca2+ ion sensitive electrode. The Ca2+ activity had a peak at a degree of
      neutralization of 0.5 and decreased with increasing Ca(OH)2 concentration beyond
      it when the polymer solution was neutralized with Ca(OH)2. The decrease in the
      Ca2+ activity was not observed when the polymer concentration was very low. The
      counter ion condensation theory did not hold for this solution except in the case
      of an extremely dilute solution. The additivity rule for Ca2+ was confirmed for
      this solution. When the maleic acid copolymer was neutralized with both Ca(OH)2
      and KOH, the Ca2+ activity had a peak at a degree of neutralization of 0.5 when
      neutralization with KOH was less than 0.3 and the Ca2+ activity decreased more
      drastically than that neutralized with only Ca(OH)2. The appearance of the peak
      of the Ca2+ activity at a degree of neutralization of 0.5 was independent of the
      ratio of Ca2+ concentration to polymer concentration or absolute Ca2+
      concentration, but depended on the degree of ionization, i.e., linear electric
      charge density on the polymer because of ionization of the carboxyl groups.
      Interpretations of the behavior of the Ca2+ activity are discussed.

PMID- 17020850
TI  - Control in channelled pathways. A matrix method calculating the enzyme control
      coefficients.
AB  - The usual equations expressing the enzyme control coefficients (quantitative
      indicators of 'global' control properties of a pathway) via the elasticity
      coefficients (reflecting local kinetic properties of an enzyme reaction), cannot
      be applied to a variety of 'non-ideal' pathways, in particular to pathways with
      metabolic channelling. Here we show that the relationship between the control and
      elasticity coefficients can be obtained by considering such a metabolic pathway
      as a network of elemental chemical conversions (steps). To calculate the control
      coefficients of enzymes one should first determine the elasticity coefficients of
      such elemental steps and then take their appropriate combinations. Although the
      method is illustrated for a channelled pathway it can be used for any non-ideal
      pathway including those with high enzyme concentrations where the sequestration
      of metabolites by enzymes cannot be neglected.

PMID- 17020851
TI  - Enthalpy changes in the formation of the proton electrochemical potential and its
      components.
AB  - Enthalpy changes in the formation of a proton electrochemical potential (Delta mu
      H+) and its components, DeltapH (proton gradient) and Deltapsi (electrical
      potential), across two types of E. coli membrane vesicles were investigated. Flow
      dialysis experiments showed that in 0.1 M KPi, pH 6.6, E. coli GR19N membrane
      vesicles coupled with d-lactate exhibited 57 mV for DeltapH, 70 mV for Deltapsi,
      and 127 mV for Delta mu H+. Microcalorimetric measurements revealed that the
      corresponding enthalpy changes (DeltaH(pH), DeltaH(psi) and DeltaHm) were 3.5,
      3.3 and 6.9 kcal/mole, respectively. Moreover, in E. coli ML 308-225 membrane
      vesicles across which 120mV of Delta mu H+ was generated, values of DeltaH(pH)
      and DeltaH(psi) were determined as 7.0 and 6.6 kcal/mole, as compared with the
      previously reported 14.1 kcal/mole for DeltaH(m). Comparisons of these enthalpy
      data revealed that component enthalpies (DeltaH(pH) and DeltaH(psi)) essentially
      added up to the total enthalpy (DeltaHm), providing a self-consistent test for
      the obtained data. In both membranes, the ratio ofDeltaH(psi) to Deltapsi was
      comparable to that of DeltaH(pH) to DeltapH in the formation of Delta mu H+.
      These observations indicated that the process of the movement of H+ across the
      membranes was the major contributor to the observed energetic changes. Moreover,
      the enthalpy change in the formation of Delta mu H+ was compared with the
      membranes derived from GR19N and ML 308-225 and coupled with NADH and d-lactate.
      The results were discussed in terms of trans-membrane phenomena.

PMID- 17020852
TI  - Intrinsic binding effects in mixed counterionic polyelectrolyte systems:
      extension of condensation theory and comparison with voltammetric data.
AB  - Voltammetric speciation data for the potassium/zinc/polymethacrylate system,
      recently obtained for various charge densities of the polyelectrolyte (Diaz-Cruz
      et al., Anal. Chim. Acta, 264 (1992) 163) and for different concentrations of
      monovalent counterions (van den Hoop and van Leeuwen, Anal. Chim. Acta, 273
      (1993) 275), are compared with theoretical predictions computed according to a
      new thermodynamic model developed by Paoletti et al. (Biophys. Chem., 41 (1991)
      73) and recently extended by Benegas and Paoletti (in preparation). The model
      allows: (i) the simultaneous condensation of both monovalent and divalent
      counterions and (ii) can account for a certain specific affinity of the
      polyelectrolyte for one type of the counterion over the other. For various charge
      densities of the polyelectrolyte, experimentally obtained speciation data for the
      K/Zn/PMA system agree well with theoretical predictions by considering an extra
      reduced molar affinity energy of -4RT for the Zn(2+) polyelectrolyte binding. The
      agreement between experimental and theoretical values for the distribution of
      Zn(2+) ions over the free and bound state becomes less perfect for relatively
      high concentrations of monovalent counterions.

PMID- 17020853
TI  - Conformational transitions in polyelectrolyte adsorption.
AB  - The mole fraction X of nucleic acid chromophores, adsorbed on cationic and
      anionic exchange chromatography paper disks, was calculated [O.L. Horer and A.
      Grigorescu, Rev. Roum. Med. Virol., 43 (1992) 33] in terms of the standard Debye
      screening length D (in the 0.01 to 1.2 M ionic strength range), using data from
      MLSEA (multiple light scattering enhanced absorption) measurements. In contrast
      to the cases of mononucleotides or double-stranded and relatively rigid DNA
      structures, highly polymerized and single-stranded RNA shows sigmoidal-shaped X
      curves, suggesting that polymer adsorption may be regarded as a conformational
      transition from a three-dimensional statistical coil to a two-dimensional one.

PMID- 17020854
TI  - Molecular dynamics of amphotericin B I. Single molecule in vacuum and water.
AB  - Molecular dynamics simulations were performed for an antifungal polyene
      antibiotic amphotericin B (AMB). A single molecule of the AMB was modeled in
      vacuum as well as in water. In the latter case it was surrounded by 354 SPC water
      molecules and a periodic boundary condition was applied. An amino-sugar
      mycosamine ring was found to be rigid in the conditions studied. The mean
      orientation of this ring in relation to a macrolide ring was found to be common
      in both simulations and similar to that observed in a crystal of N-iodoacetyl
      derivative. A large flexibility of the amino-sugar orientation was observed in
      vacuum in contrast to water simulation. Several conformers of the macrolide ring
      were observed in vacuum as well as in water simulation. Interactions which may
      force these conformational transitions have been proposed. The structuring of the
      water molecules around polar and ionizable parts of the AMB molecule were
      analysed. The influence of the dynamic behavior of the AMB on structures of
      supramolecular complexes containing this antibiotic is discussed.

PMID- 17020855
TI  - Effect of methylation on the pyrimidine-pyrimidine stacking interaction studied
      by (1)H NMR chemical shift.
AB  - Mutually induced proton chemical shift changes were measured for the mixed
      solutions of pyrimidine and its methylated forms in deuterium oxide at 35 degrees
      C. The chemical shift vs. concentration profiles were analyzed using a three
      state decomposition model based on competitive self- and hetero-association dimer
      equilibria. The equilibrium constants show an increasing association tendency
      within the series pyrimidine-5-methyl-pyrimidine (0.23 +/- 0.02 M(-1)) <
      pyrimidine-4,6-dimethyl-pyrimidine (0.32 +/- 0.04 M(-1)) < 5-methyl-pyrimidine
      4,6-dimethyl-pyrimidine (0.51 +/- 0.04 M(-1)). The upfield dimer shifts suggest
      an offset stacked geometry for the structure of associations between the parent
      molecule of the pyrimidine nucleobases and its methylated derivatives in aqueous
      solution.

PMID- 17020856
TI  - Differential scanning calorimetric studies on binding of N-acetyl-D-glucosamine
      to lysozyme.
AB  - Differential scanning calorimetric (DSC) measurements were performed on the
      thermal denaturation of lysozyme and lysozyme complexed with N-acetyl-D
      glucosamine (GlcNAc) at pH 5.00 (acetate buffer), 4.25 and 2.25 (Gly-HCl buffer).
      DSC data have been analyzed to obtain denaturation temperature T(d), enthalpy of
      denaturation DeltaH(D), heat capacity of denaturation DeltaC(pd) and
      cooperativity index eta. From these thermodynamic parameters, the binding
      constant K(L) and enthalpy of binding DeltaH(L), for the weak binding of lysozyme
      with GlcNAc have been determined. The values of K(L) and DeltaH(L) at pH 5.00 and
      298 K are 42 +/- 4 M(-1) and -24 +/- 4 kJ mol(-1), respectively, and agree very
      well with the experimentally determined values from equilibrium and other
      studies. The binding constant has also been estimated by simulating the DSC curve
      with varying values of K(L) (T(d)) until it matches the experimental curve.

PMID- 17020857
TI  - Direct reconstitution of bacteriorhodopsin into planar phospholipid bilayers-
      detergent effect.
AB  - This paper describes how the structure and concentration level of a detergent
      used for substitution after bacteriorhodopsin (bR) solubilization affect the
      reconstitution of the bR into phospholipid planar bilayers. A direct insertion
      method was used for the bR reconstitution into the bilayers. Two detergents
      representing the two major types were used: sodium deoxycholate with a cholane
      ring structure, and octylglucoside with a linear (or chain) structure. We then
      characterized the reconstitution for the two detergents by considering the
      detergent separation profiles and the photocurrent variations upon addition of
      lanthanum chloride and the protonophore FCCP (carbonylcyanide-p
      trifluoromethoxyphenylhydrazone). We found that for successful transmembrane
      reconstitution of bR the detergent with the cholane-ring structure was preferable
      to that with the linear structure when the detergent concentration was above its
      critical micellar concentration. This preference was explained by the ease with
      which the detergent with the cholane-ring structure was removed from protein
      compared to that with the linear structure. Finally, we proposed a scheme for the
      reconstitution of the protein.

PMID- 17020858
TI  - Nonenzymatic hydrolysis of adenosinetriphosphate (ATP) at high temperatures and
      high pressures.
AB  - Marine organisms living in the deep sea near to hot wells show a fascinating
      tolerance to extremely high temperatures and pressures. Under the given
      conditions the synthesis and stability of biomolecules seem to be limiting facts
      for the basis of life. We studied the influence of high pressures and high
      temperatures on the hydrolysis of ATP, a universal component for the storage of
      energy in all known organisms and therefore an extremely interesting and
      important molecule. The hydrolysis of ATP, ADP and AMP was studied in unbuffered
      solutions at temperatures between 353 and 369 K at pH values between 3.4 and
      10.0. The pressure dependence was determined to p(max) = 220 MPa also at pH 5.
      All data can be explained by a proton catalyzed mechanism that removes in
      consecutive steps the final phosphate group. In none of the experiments could
      pyrophosphate be detected. The influence of phosphate and magnesium ions on the
      hydrolysis is discussed.

PMID- 17020860
TI  - Discontinuous formation and desorption of clusters during particles adsorption at
      surfaces.
AB  - A theoretical model was derived to describe the discontinuous formation and
      desorption of clusters during particle adsorption at surfaces. Two steps were
      investigated: (1) time-dependent adsorption, where we found that the initial
      slope and the limiting magnitude of an adsorption isotherm depend on the
      clusters' distribution. A higher magnitude of both the adsorption and desorption
      rates appear to contract the time scale and hence increase the initial slope.
      Decreasing the geometrical parameter, q, which represents the shape of an
      adsorbed cluster, enhances the growth of large clusters on the surface. (2) A
      concentration dependence model shows that the number of adsorbed molecules
      increases with increases in the value of n (nucleation capacity). Furthermore,
      higher rates of adsorption provide steeper initial slopes (higher affinity of,
      molecules to surface). Decreasing q from 2 to 1, i.e. from a circular to a linear
      cluster formation, slightly decreases the magnitude of the isotherms.

PMID- 17020861
TI  - Solution structure of glyceraldehyde-3-phosphate dehydrogenase from Haloarcula
      vallismortis.
AB  - The subunit molecular mass of glyceraldehyde-3-phosphate dehydrogenase from the
      extreme halophile Haloarcula vallismortis (hGAPDH) was determined by mass
      spectrometry to be 35990 +/- 80 daltons, similar to other GAPDHs. Complementary
      density, sedimentation and light scattering experiments showed the protein to be
      a tetramer that binds 0.18 +/- 0.10 gram of water and 0.07 +/- 0.02 gram of KCl
      per gram of protein, in multimolar KCl solutions. At low salt (below 1 M), the
      tetramer dissociated into unfolded monomers. This is the third halophilic protein
      for which solvent interactions were measured. The extent of these interactions
      depends on the protein, but all form an invariant particle, in multimolar NaCl or
      KCl solutions, that binds a high proportion of salt when compared to non
      halophilic proteins.

PMID- 17020862
TI  - Study of pH and temperature-induced transitions in urate oxidase (Uox-EC1.7.3.3)
      by microcalorimetry (DSC), size exclusion chromatography (SEC) and enzymatic
      activity experiments.
AB  - Purified recombinant urate oxidase (urate oxygen oxidoreductase EC 1.7.3.3. re
      Uox) has been studied by means of differential scanning calorimetry (DSC) in
      correlation with enzymatic activity measurements and size exclusion
      chromatography. Differential scanning calorimetry curves versus pH show two
      endothermal effects in the pH range 6-10. The first endotherm reveals a maximum
      stability between pH 7.25 and pH 9.5 corresponding to a temperature of transition
      T(m1) of 49.0 degrees C and an enthalpy of transition of 326 kJ mol(-1). This
      value dramatically decreases below pH 7.25. The behavior of the second endotherm
      is more complex but the temperature of transition T(m2) is constant between pH 9
      and 7.25 and a maximum for the corresponding enthalpy is obtained near pH 8 with
      DeltaH(2)=272 kJ mol(-1). An optimal pH of 8.0 for the stability of the enzymatic
      activity at elevated temperature was also found which was in good agreement with
      calorimetric results. Reversibility of the first endotherm is obtained from 20 to
      51.5 degrees C. The calorimetric result is correlated to enzymatic activity,
      purity by size exclusion chromatography (SEC) and protein concentration
      measurements. In contrast, for the second endotherm, after heating up to 68.9
      degrees C, no reversibility was found. Interaction with structural analogues of
      urate has been studied by DSC. 8-Azahyooxanthine has only a small effect and
      caffeine has no effect at all. With 8-azaxanthine, a rapid increase of the T(m1)
      function of the concentration is obtained. At high concentration T(m1) reached
      the T(m2) value which remained unaffected.

PMID- 17020863
TI  - Pre-steady-state kinetics and modelling of the oxygenase and cyclooxygenase
      reactions of prostaglandin endoperoxide synthase.
AB  - The pre-steady-state kinetics of the prostaglandin endoperoxide synthase
      oxygenase reaction with eicosadienoic acids and the cyclooxygenase reaction with
      arachidonic acid were investigated by stopped-flow spectrophotometry at 426 nm,
      an isosbestic point between native enzyme and compound I. A similar reaction
      mechanism for both types of catalysis is defined from combined kinetic
      experiments and numerical simulations. In the first step a fatty acid
      hydroperoxide reacts with the native enzyme to form compound I and the fatty acid
      hydroxide. In the second step the fatty acid reduces compound I to compound II
      and a fatty acid carbon radical is formed. This is followed by two fast steps:
      (1) the addition of either one molecule of oxygen (the oxygenase reaction) or two
      molecules of oxygen (the cyclooxygenase reaction) to the fatty acid carbon
      radical to form the corresponding hydroperoxyl radical, and (2) the reaction of
      the hydroperoxyl radical with compound II to form the fatty acid hydroperoxide
      and a compound I-protein radical. A unimolecular reaction of the compound I
      protein radical to reform the native enzyme is assumed for the last step in the
      cycle. This is a slow reaction not significantly affecting steps 1 and 2 under
      pre-steady-state conditions. A linear dependence of the observed pseudo-first
      order rate constant, k(obs), on fatty acid concentration is quantitatively
      reproduced by the model for both the oxygenase and cyclooxygenase reactions. The
      simulated second order rate constants for the conversion of native enzyme to
      compound I with arachidonic or eicosadienoic acids hydroperoxides as a substrate
      are 8 x 10(7) and 4 x 10(7) M(-1) s(-1), respectively. The simulated and
      experimentally obtained second-order rate constants for the conversion of
      compound I to compound II with arachidonic and eicosadienoic acids as a substrate
      are 1.2 x 10(5) and 3.0 x 10(5) M(-1) s(-1), respectively.

PMID- 17020864
TI  - Stability of emulsions stabilised by two physiological surfactants: L-alpha
      phosphatidylcholine and sodium taurocholate.
AB  - The emulsion phase formed within the stomach and duodenum during digestion of a
      fatty meal has been modelled using two physiological surfactants, the
      phospholipid L-alpha-phosphatidylcholine (PC) and the bile salt sodium
      taurocholate (NaT). Upon dilution of the phospholipid stabilised emulsions with a
      solution of NaT the bile salt became incorporated into the oil/water interface
      imparting a negative charge to the droplet surface. The magnitude of the droplet
      microelectrophoretic mobility for the mixed PC and NaT system was 47% of that
      found for emulsion droplets stabilised by NaT alone. But the electrostatic
      repulsion between droplets was not sufficient to account for the observed
      improvement in emulsion stability to coalescence. It is suggested that a residual
      liquid crystalline phospholipid interface is present imparting a significant
      steric component to the stabilisation of the emulsions droplets.

PMID- 17020866
TI  - Biophysical view of the role of interfaces in biomolecular recognition.
AB  - Molecular recognition plays a key role in life. Macromolecular interactions at
      and with interfaces are of paramount importance in this respect. It is therefore
      crucial to understand and quantify the forces near the surfaces of biological
      interest in sufficient detail. Specific binding of large molecules, such as
      antibodies, is affected by the proximity of polar surfaces, for example. On the
      one hand, the presence of the net surface charges may raise or lower the local
      macromolecular concentration depending on the relative sign of the charges
      involved. On the other hand, the ligands attached to strongly polar surfaces
      always attract and bind their corresponding antibodies less efficiently than the
      corresponding dissolved molecules. The reason for this is the non-Coulombic
      repulsion between the ligand-presenting polar surface and the approaching
      macromolecule. This force is promoted by the surface hydrophilicity and the width
      of the interfacial region. A simple, direct hydration force is seldom, if ever,
      seen in such systems. (This is owing to the very short range (Lambda (h ) reverse
      similar 0.1 nm ) of pure hydration force.) The non-specific adsorption of
      proteins to the lipid bilayer is also little affected by the overall repulsion
      between the macromolecule and the bilayer surface; such an adsorption is governed
      more by the number of defects and/or by the availability of the hydrophobic
      binding sites in the interfacial region. Artificial lipid membranes typically
      offer numerous such binding sites to the surrounding macromolecules. Multiple non
      specific protein adsorption, which results in partial macromolecular denaturation
      or complement activation, is therefore one of the main reasons for the rapid
      elimination of lipid vesicles from the blood stream in vivo. To promote the
      circulation time of an intravenously injected lipid suspension it is therefore
      necessary to modify the surfaces of their constituent lipid bilayers. Increasing
      the surface net charge density and/or increasing the bilayer surface
      hydrophilicity is of little use in this respect. In order to affect the non
      specific bilayer-protein interactions significantly, an optimal number of water
      soluble, short and sufficiently mobile polymers must be attached to the lipid
      head-groups. These polymers then increase the repulsive barrier of the membrane
      surface dramatically, due to the generation of a thick and mobile as well as
      strongly hydrated interface. Owing to this, the affinity for proteins of the
      resulting surface is lowered and the surface-induced protein denaturation or
      complement insertion is hampered. Polymer-coated liposomes, consequently, are not
      attractive for the phagocytic cells. Such liposomes, consequently, remain in the
      blood circulation much longer than simple lipid vesicles; the former,
      consequently, may spontaneously accumulate in tumors.

PMID- 17020867
TI  - The computer as a laboratory for the physical chemistry of membranes.
AB  - A mini-review is given of some recent advances in the use of computer-simulation
      approaches to the study of physico-chemical properties of lipid bilayers and
      biological membranes. The simulations are based on microscopic molecular
      interaction models as well as random-surface models of fluid membranes.
      Particular emphasis is put on those properties that are controlled by the many
      particle character of the lamellar membrane, i.e. correlations and fluctuations
      in density, composition and large-scale conformational structure. It is discussed
      how dynamic membrane heterogeneity arises and how it is affected by various
      molecular species interacting with membranes, such as cholesterol, drugs,
      insecticides, as well as polypeptides and integral membrane proteins. The
      influence of bending rigidity and osmotic-pressure gradients on large-scale
      membrane conformation and topology is described.

PMID- 17020868
TI  - On the hydrodynamic analysis of macromolecular conformation.
AB  - Hydrodynamics provides a powerful complementary role to the traditional "high
      resolution" techniques for the investigation of macromolecular conformation,
      especially in dilute solution, conditions which are generally inaccessible to
      other structural techniques. This paper describes the state of art of
      hydrodynamic representations for macromolecular conformation, in terms of (1)
      simple but straightforward ellipsoid of revolution modelling; (2) general
      triaxial ellipsoid modelling; (3) hydrodynamic bead modelling; (4) the ability,
      especially for polydisperse macromolecular systems, to distinguish between
      various conformation types; (5) analysis of macromolecular flexibility.

PMID- 17020869
TI  - A theoretical and experimental investigation of the electronic spectra and
      tautomerization of nucleobases.
AB  - The electronic structures of all possible tautomers of uracil, thymine, cytosine,
      adenine and guanine have been carefully examined within the MNDO-MO frame-work.
      Equilibrium geometries are determined and the relative stabilities are discussed.
      Allowance for solvent effect on the stabilities is made by assuming a tetrahedral
      solvent cage with the DNA base occupying its centre. The electronic absorption
      spectra of the studied DNA bases, in solvents of different polarities are
      recorded and discussed. Assignments of the observed bands are facilitated using
      MNDO-CI computations. It is suggested that in solution the DNA bases are in some
      statistical mixtures of the most stable tautomers, and the Watson-Crick (WC)
      structure cannot account for the observed spectra alone.

PMID- 17020870
TI  - Solution X-ray scattering study of reconstitution process of tobacco mosaic virus
      particle using low-temperature quenching.
AB  - The reconstitution process of tobacco mosaic virus (TMV) was investigated by the
      solution X-ray scattering measurements with the synchrotron radiation source
      using low-temperature quenching. TMV assembly in an aqueous solution is
      completely stopped below 5 degrees C. The TMV assembly was traced by the small
      angle X-ray scattering (SAXS) measurements at 5 degrees C on a series of
      solutions prepared by low-temperature quenching after incubation either at 15, 20
      or 25 degrees C for an appropriate interval between 0 and 60 min. The SAXS
      results were analyzed by the Guinier plot, the Kratky plot and the distance
      distribution function. In order to account the time course of SAXS profiles in
      terms of the elongation of TMV assembly, a model calculation was performed to
      simulate the Guinier plot, the Kratky plot and the distance distribution function
      by applying Glatter's multibody method using models that were constituted of the
      spheres representing a column of piled two-layer disks of TMV-protein. The three
      simulated functions thus obtained support the conclusion derived from the three
      functions calculated from the experimental results that the incubation of the RNA
      and protein of TMV began to reconstitute TMV instantly after mixing, proceeded
      steeply to a long rod, and then extended asymptotic to the full length of the TMV
      particle. This process is in good agreement with that obtained from electron
      microscopic studies.

PMID- 17020871
TI  - Partial molar heat capacities of the peptides glycylglycylglycine, glycyl-L
      alanylglycine and glycyl-DL-threonylglycine in aqueous solution over the
      temperature range 50 to 125 degrees C.
AB  - Partial molar heat capacities of the three tripeptides glycylglycylglycine,
      glycyl-L-alanylglycine and glycyl-DL-threonylglycine in aqueous solution at the
      temperatures 50, 75, 100 and 125 degrees C have been determined using
      differential flow calorimetry. The results have been used to estimate the
      contributions to the partial molar heat capacities of peptides of the alanyl and
      threonyl side-chains. These side-chain contributions are compared with those
      reported in the literature.

PMID- 17020872
TI  - Shock wave lithotripsy for ureteral stones in elderly male patients.
AB  - INTRODUCTION: Age has never been considered as a factor in the treatment of
      ureteral stones, but elderly male patients may suffer from concomitant illnesses
      that may affect SWL results, such as voiding difficulties and musculo-skeletal
      and cardio-vascular disorders. The aim of this study was to assess the success
      rate and complications of shock wave lithotripsy (SWL) for all size and location
      ureteral stones in patients older than 70 years of age. PATIENTS AND METHODS: We
      retrospectively reviewed the charts and radiology films of all patients who had
      undergone SWL for ureteral stones with the HM3 lithotriptor and compared the
      results of patients younger than 70 years to those older than 70 years. RESULTS:
      During 2000-2003, 238 consecutive male patients (23 older than 70 years)
      underwent SWL under regional anesthesia for all size and locations ureteral
      stones. Stone sizes, locations, opacity, and pre-operative drainage procedures
      matched in both groups. The overall stone-free rate was 91% for both groups.
      Complications were recorded in 1% of the older patients and 3.7% of the younger
      ones. No treatment-related mortality was recorded. CONCLUSIONS: Age itself has no
      effect on the success rate of SWL with the HM3 lithotripter for ureteral stones.
      In general, SWL treatment showed a high success rate with minimal morbidity and
      no treatment-related mortality.

PMID- 17020873
TI  - A case of acute promyelocytic leukemia during gefitinib treatment.

PMID- 17020874
TI  - Stored Ca2+ depletion-induced oligomerization of stromal interaction molecule 1
      (STIM1) via the EF-SAM region: An initiation mechanism for capacitive Ca2+ entry.
AB  - Stromal interaction molecule 1 (STIM1) has recently been identified as a key
      player in store-operated Ca2+ entry. Endoplasmic reticulum (ER) luminal Ca2+
      depletion results in STIM1 redistribution from ER membrane homogeneity to
      distinctly localized aggregates near the plasma membrane; these changes precede
      and are linked to cytoplasmic Ca2+ influx via Ca2+ release-activated channels
      (CRACs). The molecular mechanisms initiating ER STIM1 redistribution and plasma
      membrane CRAC activity are not well understood. We recombinantly expressed the
      Ca2+-sensing region of STIM1 consisting of the EF-hand together with the sterile
      alpha-motif (SAM) domain (EF-SAM) to investigate its Ca2+-related conformational
      and biochemical features. We demonstrate that Ca2+-loaded EF-SAM (holo) contains
      high alpha-helicity, whereas EF-SAM in the absence of Ca2+ (apo) is much less
      compact. Accordingly, the melting temperature (Tm) of the holoform is
      approximately 25 degrees C higher than apoform; heat and urea-derived
      thermodynamic parameters indicate a Ca2+-induced stabilization of 3.2 kcal mol(
      1). We show that holoEF-SAM exists as a monomer, whereas apoEF-SAM readily forms
      a dimer and/or oligomer, and that oligomer to monomer transitions and vice versa
      are at least in part mediated by changes in surface hydrophobicity. Additionally,
      we find that the Ca2+ binding affinity of EF-SAM is relatively low with an
      apparent dissociation constant (Kd) of approximately 0.2-0.6 mM and a binding
      stoichiometry of 1. Our results suggest that EF-SAM actively participates in and
      is the likely the molecular trigger initiating STIM1 punctae formation via large
      conformational changes. The low Ca2+ affinity of EF-SAM is reconciled with the
      confirmed role of STIM1 as an ER Ca2+ sensor.

PMID- 17020875
TI  - Effects of tryptophan photoproducts in the circadian timing system: searching for
      a physiological role for aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) mediates adverse effects of dioxins, but its
      physiological role remains ambiguous. The similarity between AhR and canonical
      circadian clock genes suggests potential involvement of AhR in regulation of
      circadian timing. Photoproducts of tryptophan (TRP), including 6-formylindolo[3,2
      b]carbazole (FICZ), have high affinity for AhR and are postulated as endogenous
      ligands. Although TRP photoproducts activate AhR signaling in vitro, their
      effects in vivo have not been investigated in mammals. Because TRP photoproducts
      may act as transducers of light, we examined their effects on the circadian
      clock. Intraperitoneal injection of TRP photoproducts or FICZ to C57BL/6J mice
      dose dependently induced AhR downstream targets, cytochrome P4501A1 (CYP1A1) and
      cytochrome P4501B1 mRNA expression, in liver. c-fos mRNA, a commonly used marker
      for light responses, was also induced with FICZ, and all responses were AhR
      dependent. A rat-immortalized suprachiasmatic nucleus (SCN) cell line, SCN 2.2,
      was used to examine the direct effect of TRP photoproducts on the molecular
      clock. Both TRP photoproducts and FICZ-increased CYP1A1 expression and prolonged
      FICZ incubation altered the circadian expression of clock genes (Per1, Cry1, and
      Cry2) in SCN 2.2 cells. Furthermore, FICZ inhibited glutamate-induced phase
      shifting of the mouse SCN electrical activity rhythm. Circadian light entrainment
      is critical for adjustment of the endogenous rhythm to environmental light cycle.
      Our results reveal a potential for TRP photoproducts to modulate light-dependent
      regulation of circadian rhythm through triggering of AhR signaling. This may lead
      to further understanding of toxicity of dioxins and the role of AhR in circadian
      rhythmicity.

PMID- 17020876
TI  - Bacterial bioreactors for high yield production of recombinant protein.
AB  - We developed a new bacterial expression system that utilizes a combination of
      attributes (low temperature, induction of an mRNA-specific endoribonuclease
      causing host cell growth arrest, and culture condensation) to facilitate stable,
      high level protein expression, almost 30% of total cellular protein, without
      background protein synthesis. With the use of an optimized vector, exponentially
      growing cultures could be condensed 40-fold without affecting protein yields,
      which lowered sample labeling costs to a few percent of the cost of a typical
      labeling experiment. Because the host cells were completely growth-arrested,
      toxic amino acids such as selenomethionine and fluorophenylalanine were
      efficiently incorporated into recombinant proteins in the absence of
      cytotoxicity. Therefore, this expression system using Escherichia coli as a
      bioreactor is especially well suited to structural genomics, large-scale protein
      expressions, and the production of cytotoxic proteins.

PMID- 17020877
TI  - Transmembrane segment 12 of the Glut1 glucose transporter is an outer helix and
      is not directly involved in the transport mechanism.
AB  - A model has been proposed for the exofacial configuration of the Glut1 glucose
      transporter in which eight transmembrane domains form an inner helical bundle
      stabilized by four outer helices. The role of transmembrane segment 12, predicted
      to be an outer helix in this hypothetical model, was examined by cysteine
      scanning mutagenesis and the substituted cysteine accessibility method using the
      membrane-impermeant, sulfhydryl-specific reagent, p-chloromercuribenzenesulfonate
      (pCMBS). A previously characterized functional cysteine-less Glut1 molecule was
      used to produce 21 Glut1 point mutants by changing each residue along helix 12 to
      a cysteine residue. These mutants were then expressed in Xenopus oocytes, and
      their protein levels, functional activities, and sensitivities to pCMBS were
      determined. Strikingly, in contrast to all nine other predicted Glut1
      transmembrane helices that have been previously examined by this method, none of
      the 21 helix 12 single-cysteine mutants exhibited significant inhibition of
      specific transport activity. Also unlike most other Glut1 transmembrane domains
      in which solvent-accessible residues lie along a single face of the helix,
      mutations in five consecutive residues predicted to lie close to the exofacial
      face of the membrane resulted in sensitivity to pCMBS-induced transport
      inhibition. These results suggest that helix 12 plays a passive stabilizing role
      in the structure of Glut1 and is not directly involved in the transport
      mechanism. Additionally, the pCMBS data indicate that the predicted exoplasmic
      end of helix 12 is completely exposed to the external solvent when the
      transporter is in its exofacial configuration.

PMID- 17020878
TI  - Actin filaments are required for fibripositor-mediated collagen fibril alignment
      in tendon.
AB  - Cells in tendon deposit parallel arrays of collagen fibrils to form a functional
      tissue, but how this is achieved is unknown. The cellular mechanism is thought to
      involve the formation of intracellular collagen fibrils within Golgi to plasma
      membrane carriers. This is facilitated by the intracellular processing of
      procollagen to collagen by members of the tolloid and ADAMTS families of enzymes.
      The carriers subsequently connect to the extracellular matrix via finger-like
      projections of the plasma membrane, known as fibripositors. In this study we have
      shown, using three-dimensional electron microscopy, the alignment of
      fibripositors with intracellular fibrils as well as an orientated cable of actin
      filaments lining the cytosolic face of a fibripositor. To demonstrate a specific
      role for the cytoskeleton in coordinating extracellular matrix assembly,
      cytochalasin was used to disassemble actin filaments and nocodazole or colchicine
      were used to disrupt microtubules. Microtubule disruption delayed procollagen
      transport through the secretory pathway, but fibripositor numbers were
      unaffected. Actin filament disassembly resulted in rapid loss of fibripositors
      and a subsequent disappearance of intracellular fibrils. Procollagen secretion or
      processing was not affected by cytochalasin treatment, but the parallelism of
      extracellular collagen fibrils was altered. In this case a significant proportion
      of collagen fibrils were found to no longer be orientated with the long axis of
      the tendon. The results suggest an important role for the actin cytoskeleton in
      the alignment and organization of the collagenous extracellular matrix in
      embryonic tendon.

PMID- 17020879
TI  - Correction of apolipoprotein A-I-mediated lipid efflux and high density
      lipoprotein particle formation in human Niemann-Pick type C disease fibroblasts.
AB  - Impaired cell cholesterol trafficking in Niemann-Pick type C (NPC) disease
      results in the first known instance of impaired regulation of the ATP-binding
      cassette transporter A1 (ABCA1), a lipid transporter mediating the rate-limiting
      step in high density lipoprotein (HDL) formation, as a cause of low plasma HDL
      cholesterol in humans. We show here that treatment of human NPC1(-/-) fibroblasts
      with the liver X receptor (LXR) agonist TO-901317 increases ABCA1 expression and
      activity in human NPC1(-/-) fibroblasts, as indicated by near normalization of
      efflux of radiolabeled phosphatidylcholine and a marked increase in efflux of
      cholesterol mass to apoA-I. LXR agonist treatment prior to and during apoA-I
      incubation resulted in reduction in filipin staining of unesterified cholesterol
      in late endosomes/lysosomes, as well as cholesterol mass, in NPC1(-/-) cells. HDL
      species in human NPC disease plasma showed the same pattern of diminished large,
      cholesterol-rich alpha-1 HDL particles as seen in isolated heterozygous ABCA1
      deficiency. Incubating NPC1(-/-) fibroblasts with the LXR agonist normalized the
      pattern of HDL particle formation by these cells. ABCG1, another LXR target gene
      involved in cholesterol efflux to HDL, also showed diminished expression in NPC1(
      /-) fibroblasts and increased expression upon LXR agonist treatment. These
      results suggest that NPC1 mutations can be largely bypassed and that NPC1 protein
      function is non-essential for the trafficking and removal of cellular cholesterol
      if the down-stream defects in ABCA1 and ABCG1 regulation in NPC disease cells are
      corrected using an LXR agonist.

PMID- 17020880
TI  - Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain.
AB  - The CIN85/CMS (human homologs of mouse SH3KBP1/CD2AP) family of endocytic adaptor
      proteins has the ability to engage multiple effectors and couple cargo
      trafficking with the cytoskeleton. CIN85 and CMS (Cas ligand with multiple Src
      homology 3 (SH3) domains) facilitate the formation of large multiprotein
      complexes required for an efficient internalization of cell surface receptors. It
      has recently been shown that c-Cbl/Cbl-b could mediate the formation of a ternary
      complex between one c-Cbl/Cbl-b molecule and two SH3 domains of CIN85, important
      for the ability of Cbl to promote epidermal growth factor receptor down
      regulation. To further investigate whether multimerization is conserved within
      the family of adaptor proteins, we have solved the crystal structures of the CMS
      N-terminal SH3 domain-forming complexes with Cbl-b- and CD2-derived peptides.
      Together with biochemical evidence, the structures support the notion that,
      despite clear differences in the interaction surface, both Cbl-b and CD2 can
      mediate multimerization of N-terminal CMS SH3 domains. Detailed analyses on the
      interacting surfaces also provide the basis for a differential Cbl-b molecular
      recognition of CMS and CIN85.

PMID- 17020881
TI  - Rho kinase differentially regulates phosphorylation of nonmuscle myosin II
      isoforms A and B during cell rounding and migration.
AB  - The actin-myosin cytoskeleton is generally accepted to produce the contractile
      forces necessary for cellular processes such as cell rounding and migration. All
      vertebrates examined to date are known to express at least two isoforms of non
      muscle myosin II, referred to as myosin IIA and myosin IIB. Studies of myosin IIA
      and IIB in cultured cells and null mice suggest that these isoforms perform
      distinct functions. However, how each myosin II isoform contributes individually
      to all the cellular functions attributed to "myosin II" has yet to be fully
      characterized. Using isoform-specific small-interfering RNAs, we found that
      depletion of either isoform resulted in opposing migration phenotypes, with
      myosin IIA- and IIB-depleted cells exhibiting higher and lower wound healing
      migration rates, respectively. In addition, myosin IIA-depleted cells
      demonstrated impaired thrombin-induced cell rounding and undertook a more motile
      morphology, exhibiting decreased amounts of stress fibers and focal adhesions,
      with concomitant increases in cellular protrusions. Cells depleted of myosin IIB,
      however, were efficient in thrombin-induced cell rounding, displayed a more
      retractile phenotype, and maintained focal adhesions but only in the periphery.
      Last, we present evidence that Rho kinase preferentially regulates
      phosphorylation of the regulatory light chain associated with myosin IIA. Our
      data suggest that the myosin IIA and IIB isoforms are regulated by different
      signaling pathways to perform distinct cellular activities and that myosin IIA is
      preferentially required for Rho-mediated contractile functions.

PMID- 17020882
TI  - Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in
      C2C12 cells.
AB  - Cell surface heparan sulfate proteoglycans (HSPGs) have been implicated in bone
      morphogenetic protein (BMP)-mediated morphogenesis by regulating BMP activity and
      gradient formation. However, the direct role of HSPGs in BMP signaling is poorly
      understood. Here we show that HSPGs directly regulate BMP2-mediated
      transdifferentiation of C2C12 myoblasts into osteoblasts. HSPGs sequester BMP2 at
      the cell surface and mediate BMP2 internalization. Depletion of cell surface
      HSPGs by heparinase III treatment or decreased glycosaminoglycan chain sulfation
      with sodium chlorate enhances BMP2 morpho-genetic bioactivity. The addition of
      exogenous heparin, a widely used anticoagulant, reduced BMP2 signaling. Our
      results suggest that cell surface HSPGs mediate BMP2 internalization and modulate
      BMP2 osteogenic activity.

PMID- 17020883
TI  - Sulfur mobilization in cyanobacteria: the catalytic mechanism of L-cystine C-S
      lyase (C-DES) from synechocystis.
AB  - Sulfur mobilization represents one of the key steps in ubiquitous Fe-S clusters
      assembly and is performed by a recently characterized set of proteins
      encompassing cysteine desulfurases, assembly factors, and shuttle proteins.
      Despite the evolutionary conservation of these proteins, some degree of
      variability among organisms was observed, which might reflect functional
      specialization. L-Cyst(e)ine lyase (C-DES), a pyridoxal 5'-phosphatedependent
      enzyme identified in the cyanobacterium Synechocystis, was reported to use
      preferentially cystine over cysteine with production of cysteine persulfide,
      pyruvate, and ammonia. In this study, we demonstrate that C-DES sequences are
      present in all cyanobacterial genomes and constitute a new family of sulfur
      mobilizing enzymes, distinct from cysteine desulfurases. The functional
      properties of C-DES from Synechocystis sp. PCC 6714 were investigated under pre
      steady-state and steady-state conditions. Single wavelength and rapid scanning
      stopped-flow kinetic data indicate that the internal aldimine reacts with cystine
      forming an external aldimine that rapidly decays to a transient quinonoid species
      and stable tautomers of the alpha-aminoacrylate Schiff base. In the presence of
      cysteine, the transient formation of a dipolar species precedes the selective and
      stable accumulation of the enolimine tautomer of the external aldimine, with no
      formation of the alpha-aminoacrylate Schiff base under reducing conditions.
      Effective sulfur mobilization from cystine might represent a mechanism that
      allows adaptation of cyanobacteria to different environmental conditions and to
      light-dark cycles.

PMID- 17020884
TI  - Structural basis for calcium-induced inhibition of rhodopsin kinase by recoverin.
AB  - Recoverin, a member of the neuronal calcium sensor branch of the EF-hand
      superfamily, serves as a calcium sensor that regulates rhodopsin kinase (RK)
      activity in retinal rod cells. We report here the NMR structure of Ca(2+)-bound
      recoverin bound to a functional N-terminal fragment of rhodopsin kinase (residues
      1-25, called RK25). The overall main-chain structure of recoverin in the complex
      is similar to structures of Ca(2+)-bound recoverin in the absence of target
      (<1.8A root-mean-square deviation). The first eight residues of recoverin at the
      N terminus are solvent-exposed, enabling the N-terminal myristoyl group to
      interact with target membranes, and Ca(2+) is bound at the second and third EF
      hands of the protein. RK25 in the complex forms an amphipathic helix (residues 4
      16). The hydrophobic face of the RK25 helix (Val-9, Val-10, Ala-11, Ala-14, and
      Phe-15) interacts with an exposed hydrophobic groove on the surface of recoverin
      lined by side-chain atoms of Trp-31, Phe-35, Phe-49, Ile-52, Tyr-53, Phe-56, Phe
      57, Tyr-86, and Leu-90. Residues of recoverin that contact RK25 are highly
      conserved, suggesting a similar target binding site structure in all neuronal
      calcium sensor proteins. Site-specific mutagenesis and deletion analysis confirm
      that the hydrophobic residues at the interface are necessary and sufficient for
      binding. The recoverin-RK25 complex exhibits Ca(2+)-induced binding to rhodopsin
      immobilized on concanavalin-A resin. We propose that Ca(2+)-bound recoverin is
      bound between rhodopsin and RK in a ternary complex on rod outer segment disk
      membranes, thereby blocking RK interaction with rhodopsin at high Ca(2+).

PMID- 17020885
TI  - Reversed functional organization of mouse and human APOBEC3 cytidine deaminase
      domains.
AB  - APOBEC3 proteins comprise a multigene family of antiviral cytidine deaminases
      that are active against human immunodeficiency virus, simian immunodeficiency
      virus, endogenous retroelements. The Vif protein of lentiviruses binds to
      specific APOBEC3 proteins, notably A3F and A3G, to induce their degradation by
      proteasomes. APOBEC3 proteins are of two types, those with a single deaminase
      domain such as human (h)A3A and hA3C and those with two cytidine deaminase
      domains (CDD) such as hA3G, hA3F, hA3B and the mouse APOBEC3, mA3. In hA3G, both
      active sites are required for antiviral function but serve separate functions.
      CDD2 mediates the C to U deamination of the human immunodeficiency virus type 1
      genome, whereas CDD1 binds the viral RNA to allow for virion packaging. Here we
      analyzed the role of the two domains in additional APOBEC3 family members. We
      analyzed APOBEC3 proteins in which either the critical glutamic acid residue or
      the Zn(2+) coordination amino acid residues in the active sites were mutated. The
      separation of function of the domains is maintained in hA3B and hA3F, but in the
      mouse protein mA3, the roles of the two domains are reversed. Deamination is
      mediated by CDD1, whereas encapsidation and dimerization are mediated by CDD2.
      Antiviral function of each of the APOBEC3 proteins was largely attributable to
      deaminase activity. Deaminase-independent antiviral activity of the active site
      mutants was minor. These findings suggest that the two active sites have
      different functions but that these functions can be interchanged in different
      APOBEC3 family members.

PMID- 17020886
TI  - A control switch for prothrombinase: characterization of a hirudin-like
      pentapeptide from the COOH terminus of factor Va heavy chain that regulates the
      rate and pathway for prothrombin activation.
AB  - Membrane-bound factor Xa alone catalyzes prothrombin activation following initial
      cleavage at Arg(271) and prethrombin 2 formation (pre2 pathway). Factor Va
      directs prothrombin activation by factor Xa through the meizothrombin pathway,
      characterized by initial cleavage at Arg(320) (meizo pathway). We have shown
      previously that a pentapeptide encompassing amino acid sequence 695-699 from the
      COOH terminus of the heavy chain of factor Va (Asp-Tyr-Asp-Tyr-Gln, DYDYQ)
      inhibits prothrombin activation by prothrombinase in a competitive manner with
      respect to substrate. To understand the mechanism of inhibition of thrombin
      formation by DYDYQ, we have studied prothrombin activation by gel
      electrophoresis. Titration of plasma-derived prothrombin activation by
      prothrombinase, with increasing concentrations of peptide, resulted in complete
      inhibition of the meizo pathway. However, thrombin formation still occurred
      through the pre2 pathway. These data demonstrate that the peptide preferentially
      inhibits initial cleavage of prothrombin by prothrombinase at Arg(320). These
      findings were corroborated by studying the activation of recombinant mutant
      prothrombin molecules rMZ-II (R155A/R284A/R271A) and rP2-II (R155A/R284A/R320A)
      which can be only cleaved at Arg(320) and Arg(271), respectively. Cleavage of rMZ
      II by prothrombinase was completely inhibited by low concentrations of DYDYQ,
      whereas high concentrations of pentapeptide were required to inhibit cleavage of
      rP2-II. The pentapeptide also interfered with prothrombin cleavage by membrane
      bound factor Xa alone in the absence of factor Va increasing the rate for
      cleavage at Arg(271) of plasma-derived prothrombin or rP2-II. Our data
      demonstrate that pentapeptide DYDYQ has opposing effects on membrane-bound factor
      Xa for prothrombin cleavage, depending on the incorporation of factor Va in
      prothrombinase.

PMID- 17020887
TI  - Resistance to nitric oxide-induced necrosis in heme oxygenase-1 overexpressing
      pulmonary epithelial cells associated with decreased lipid peroxidation.
AB  - Increased expression of heme oxygenase-1 (HO-1) increases NO resistance in
      several cell types, although the biochemical mechanism for this protection is
      unknown. To address this issue, we have measured different molecular markers of
      nitrosative stress in three stably transfected cell lines derived from the human
      lung epithelial line A549: two lines that overexpress rat HO-1 (L1 and A4), and a
      control line with the empty vector (Neo). Compared with the control Neo cells, L1
      and A4 cells had, respectively, 5.8- and 3.8-fold greater HO activity accompanied
      by increased resistance to NO-induced necrosis. Compared with the Neo control,
      the HO-1-overexpressing cells also showed significantly less lipid peroxide
      formation and decreased perturbation of transition metal oxidation and
      coordination states following a cytotoxic NO exposure. These effects were blocked
      by the HO-1 inhibitors Zn- and Sn-protoporphyrin IX. In contrast, HO-1
      overexpression did not significantly affect total reactive oxygen or nitrogen
      species, the levels of the nucleobase deamination products in DNA (xanthine,
      inosine, and uracil) following NO exposure, or NO-induced protein nitration.
      While increased HO-1 activity prevented NO-induced fluctuations in transition
      metal homeostasis, addition of an iron chelator decreased NO toxicity only
      slightly. Our results indicate that lipid peroxidation is a significant cause of
      NO-induced necrosis in human lung epithelial cells, and that the increased NO
      survival of L1 cells is due at least in part to decreased lipid peroxidation
      mediated by HO-1-generated biliverdin or bilirubin.

PMID- 17020888
TI  - Lymphocyte responses in acute coronary syndromes: lack of regulation spawns
      deviant behaviour.

PMID- 17020889
TI  - Mortality in randomized controlled trials comparing drug-eluting vs. bare metal
      stents in coronary artery disease: a meta-analysis.
AB  - AIMS: To evaluate the effect of drug-eluting vs. bare metal stents for the
      treatment of coronary artery disease on overall, cardiac, and non-cardiac
      mortalities. METHODS AND RESULTS: We conducted a systematic literature search to
      identify all randomized controlled trials comparing sirolimus or paclitaxel
      eluting stents with bare metal stents and reporting mortality data after at least
      1 year of follow-up. Trial data were reviewed and extracted independently by two
      investigators in an unblinded standardized manner. Seventeen trials including a
      total of 8221 patients were analysed. Peto's odds ratios (ORs) for total
      mortality after 1 (n=8221), 2 (n=4631), 3 (n=4105), and 4 (n=1293) years of
      follow-up were 0.94 [95% confidence interval (CI) 0.66-1.34], 1.11 (95% CI 0.76
      1.61), 1.25 (95% CI 0.91-1.73), and 1.46 (95% CI 0.92-2.31), respectively.
      Corresponding ORs for non-cardiac mortality were 1.07 (95% CI 0.64-1.80), 1.72
      (95% CI 1.01-2.94), 1.45 (95% CI 0.93-2.25), and 1.65 (95% CI 0.89-3.10). There
      was no difference in OR for cardiac mortality among all trials. In sensitivity
      analyses, sirolimus- but not paclitaxel-eluting stents were associated with an
      increase in non-cardiac mortality at 2 and 3 years of follow-up. CONCLUSION: Drug
      eluting stents for the treatment of coronary artery disease do not reduce total
      mortality when compared with bare metal stents. Preliminary evidence suggests
      that sirolimus- but not paclitaxel-eluting stents may lead to increased non
      cardiac mortality. Long-term follow-up and assessment of cause-specific deaths in
      patients receiving drug-eluting stents is mandatory to determine the long-term
      safety of these devices.

PMID- 17020890
TI  - Kommerell's aneurysm.

PMID- 17020891
TI  - Atypical presentation and unrecognized myocardial infarction.

PMID- 17020892
TI  - Coronary artery perforation complicated by cardiac rupture during conventional
      PCI.

PMID- 17020893
TI  - Chlamydia trachomatis and Neisseria gonorrhoeae infection and the sexual
      behaviour of men who have sex with men.
AB  - BACKGROUND: Rates of bacterial sexually transmitted infections (STIs) continue to
      rise among men who have sex with men (MSM) in the UK. OBJECTIVE: To evaluate
      factors associated with Chlamydia trachomatis and Neisseria gonorrhoeae among MSM
      attending a genitourinary medicine clinic in inner London. STUDY DESIGN: 599 MSM
      undergoing testing for STIs were recruited. Specimens for ligase chain reaction
      (LCR), strand displacement amplification (SDA) assay and culture were collected
      from the pharynx, urethra and rectum for the detection of C trachomatis and N
      gonorrhoeae. Details regarding demographics, symptoms, signs and sexual behaviour
      were recorded. Associations of these factors with each infection were tested,
      adjusting for other risk factors. RESULTS: The prevalence of C trachomatis and N
      gonorrhoeae was 11.0% and 16.0%, respectively. LCR and SDA performed well for the
      detection of C trachomatis and N gonorrhoeae from urethra and rectum. Using
      either method, compared with our current testing policy, over 18% of those with C
      trachomatis and N gonorrhoeae would not have had their infection diagnosed or
      treated. Age, sexual behaviour, urethral and rectal symptoms and signs were
      strongly associated with both infections. A total of 33.7% of men reported at
      least one episode of unprotected anal intercourse in the previous month. Men
      reporting multiple episodes were markedly more likely to be HIV positive.
      CONCLUSION: The prevalence of infection, rates of partner acquisition and
      unprotected anal intercourse reported among these MSM are alarming. Improved
      detection of C trachomatis and N gonorrhoeae using nucleic acid amplification
      tests has major public health implications for STI and possibly HIV transmission
      in this population.

PMID- 17020894
TI  - Long-term functional outcome of brachytherapy for carcinoma of the mobile tongue:
      focus on the atrophic change of irradiated tongue.
AB  - OBJECTIVE: To assess tongue atrophy and long-term functional outcome of mobile
      tongue cancer patients after interstitial radiotherapy. METHODS: Of 493 patients
      whose squamous cell carcinoma of the mobile tongue had been treated with low dose
      rate brachytherapy, there were 57 patients evaluated between July 2002 and April
      2004 whose tongue had not been modified by surgical procedures and who had no
      primary recurrence. The median time from treatment to evaluation was 96 months
      (range: 9-214 months). Almost all of the patients belonged to the early stage
      tongue cancer (T1/T2/T3/T4=30:24:3:0), and all had received interstitial
      radiotherapy with a single-plane implant. To evaluate the deformity of the
      tongue, we used a grading system that classified the atrophic changes of the
      tongue into four categories (G0-G3). RESULTS: Thirty-nine patients (70%) showed
      mild tongue hemiatrophy (G1 or G2) in the irradiated side. However, no patients
      showed severe atrophy where the tongue cannot be made to protrude beyond the
      incisors (G3). The length of time after brachytherapy was >72 months and the age
      of the patients at brachytherapy had the same statistical significance
      (P=0.0366). As for functional outcome, understandability of speech and a normal
      diet were preserved for almost all patients. CONCLUSION: The progression of
      atrophic change in the irradiated tongue occurred over a long term after
      brachytherapy. However, most patients could maintain their activities of daily
      life without severe restriction.

PMID- 17020895
TI  - Preoperative chemoradiotherapy for esophageal cancer enhances the postoperative
      systemic inflammatory response.
AB  - BACKGROUND: Chemoradiotherapy (CRT) has been established to improve the long-term
      survival in patients with esophageal carcinoma. However, little is known about
      whether preoperative CRT may affect the postoperative systemic response. METHODS:
      We investigated the postoperative clinical course in terms of the systemic
      inflammatory response syndrome (SIRS) in patients with preoperative CRT (CRT
      group) and surgery alone (SA group). RESULTS: Both the postoperative heart and
      respiratory rate in the CRT group were significantly higher than in the SA group.
      The duration and incidence of SIRS, as well as the number of positive criteria
      for SIRS, were significantly greater than those in the SA group. There was no
      difference in the postoperative morbidity and mortality between the two groups.
      CONCLUSIONS: Preoperative CRT was found to significantly enhance the
      postoperative SIRS, thus suggesting its potentially higher risk of complications.

PMID- 17020896
TI  - Inhibition of nuclear factor-kappa B activation attenuates hydrogen peroxide
      induced cytotoxicity in human lens epithelial cells.
AB  - AIMS: Hydrogen peroxide (H(2)O(2)) is the major oxidant involved in cataract
      formation. Lens epithelial cells have been suggested to be the first site of
      oxidative damage. The authors investigated the relationship between H(2)O(2)
      induced cytotoxicity and activation of nuclear factor kappa B (NF-kappaB) in
      human lens epithelial (HLE) cells. METHODS: HLE B-3 cells were stimulated by
      various concentrations of H(2)O(2) in the presence or absence of pyrrolidine
      dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB. H(2)O(2)-induced
      cytotoxicity was measured by lactate dehydrogenase cytotoxicity assay.
      Translocation of NF-kappaB was examined by Western blot and immunocytochemistry
      using anti-p65 antibody. RESULTS: H(2)O(2)-induced cytotoxicity increased in a
      concentration-dependent manner. PDTC treatment significantly suppressed the
      cytotoxicity induced by H(2)O(2). After stimulated with H(2)O(2), NF-kappaB was
      found translocated from cytoplasm into the nuclei. PDTC treatment also inhibited
      the translocation of NF-kappaB. CONCLUSIONS: NF-kappaB signal pathway may be
      important in the development of H(2)O(2)-induced damage in HLE cells that is
      involved in cataractogenesis.

PMID- 17020897
TI  - Observations on the management of Coats' disease: less is more.
AB  - BACKGROUND: In this article we share our experience of treating various
      severities of Coats' disease and focus on optimal therapy for advanced disease.
      METHODS: Retrospective chart review of 10 patients treated with varied techniques
      including intraocular surgery, cryopexy and/or laser photocoagulation. RESULTS:
      Nine patients were male. At presentation the average age was 4.6 years (range 21
      months-7 years), the average number of retinal quadrants involved with
      telangiectasia was 2.7 (range 1-4, median 3), eight of the 10 patients had
      retinal detachment, six of these being total, and all patients had macular
      involvement with either exudate or fibrosis. Average follow-up was 2.3 years
      (range 1-4.5 years). The best visual outcomes were observed in patients who
      presented with less severe disease. For example, the only four patients to
      maintain ambulatory vision all presented without total retinal detachment, two or
      fewer quadrants of retinal telangiectasia and a visual acuity better than light
      perception. No patient developed secondary angle closure glaucoma, and all
      patients have kept a cosmetically acceptable eye. CONCLUSION: In this limited
      series, visual outcomes in the setting of advanced Coats' disease are largely
      dependent on disease severity and visual status at the time of presentation.
      Minimally invasive surgery with vitreous infusion through the pars plana,
      combined with external drainage of subretinal fluid together with cryotherapy
      and/or laser photocoagulation is sufficient to effect retinal re-attachment and
      prevent loss of the eye.

PMID- 17020898
TI  - Invasive squamous cell carcinoma of the eyelids and periorbital region.
AB  - AIM: To review the clinical and histopathological features, treatment and
      outcomes of squamous cell carcinoma of the eyelids. METHODS: 76 patients with
      eyelid squamous cell carcinoma treated in an oncology referral hospital between
      1997 and 2006 were reviewed retrospectively. Age, sex, risk factors, duration of
      symptoms, size and location of lesion, previous recurrences, presence of
      perineural invasion (PNI) and orbital invasion, histological subtype,
      inflammatory response of peritumoral tissue were recorded and analysed. RESULTS:
      Mean (SD) lesion size was 2.4 (0.36) mm. 27 (35.5%) cases were previously
      recurrent. The most common histological subtype was well differentiated (59.2%).
      The rates of PNI and orbital invasion were 23.8% and 43.4%, respectively. 63
      patients underwent surgery, whereas others were treated with external
      radiotherapy or chemotherapy. Recurrence or presence of residual tumour rate was
      22.4%, most of them had orbital invasion. Regional lymph node metastasis was
      detected in 5 (6.6%) cases. CONCLUSIONS: Advanced deep local invasion was not
      rare in this study, as a result of treatment delay and previous inadequate
      treatments. Adverse prognostic factors associated with secondary orbital invasion
      are previous recurrences, longer duration of lesion, larger lesion size, and
      presence of PNI. Well-differentiated subtype and strong inflammatory response are
      good prognostic factors.

PMID- 17020899
TI  - Morphological characteristics of the limbal epithelial crypt.
AB  - AIM: In 2005 we reported the discovery of a novel anatomical structure at the
      limbus, which we termed the limbal epithelial crypt (LEC). The purpose of this
      study was to further evaluate the distribution, immunophenotypical, and ultra
      structural characteristics of the LEC as a putative niche of stem cells. METHODS:
      Sequential histological sections of human corneo-scleral limbal rims were
      examined for the presence and distribution of the LEC. Immunophenotypical
      characterisation of the LEC cells using a panel of antibodies of interest was
      undertaken. Transmission electron microscopy of the LEC was used to examine the
      ultra structural and morphometric features of cells within the LEC and adjacent
      limbus. RESULTS: A total of 74 LECs were identified in eight corneo-scleral rims.
      These varied in number, size and distribution within rims. Cells within the crypt
      demonstrated the following phenotype: CK3-/CK19+/CD 34-/Vimentin+/p63+/Connexin
      43+/MIB1 (Ki67)-. Presence of Cx43 was also demonstrated in the rete pegs
      adjacent to the LEC. Basal cells of the LEC were significantly smaller than basal
      cells found in adjacent rete pegs and also smaller than suprabasal limbal and
      central corneal epithelial cells (p<0.05). Morphologically they had a high
      nuclear:cytoplasmic ratio and were adherent to the underlying basement membrane
      by means of complex convolutions of cytoplasmic processes. CONCLUSIONS: LECs are
      sparse but a consistent finding in the human corneo-scleral limbus. The LEC
      contains a unique sub-population of cells expressing several characteristics that
      are consistent with it representing a putative stem cell niche.

PMID- 17020900
TI  - Inferring myopia over the lifecourse from uncorrected distance visual acuity in
      childhood.
AB  - AIM: To report the usefulness of uncorrected distance visual acuity (DVA) at 16
      years to "screen" for myopia status and to assess the lifetime risk of myopia,
      based on a national birth cohort. METHODS: 1867 members of the 1958 British birth
      cohort for whom there were data on acuity at 16 years had autorefraction, as part
      of a biomedical survey, at 45 years. Reduced uncorrected DVA at age 16 years
      (6/12 or worse in both eyes) was compared with adult refraction (spherical
      equivalent). RESULTS: Only a quarter of individuals in the population studied who
      had developed myopia by 45 years of age had reduced acuity at 16 years of age.
      Notably, half of all adults with moderate myopia (-2.99 to -5.99) and 31% (11/35)
      with severe myopia (> or =-6) had good uncorrected DVA in both eyes at 16 years
      of age. Thus, sensitivities were low, ranging from 16% for all myopia (cut-off
      point spherical equivalent -0.5) to 69% for severe myopia (cut-off point
      spherical equivalent -6). However, a high (91%) lifetime probability of primary
      myopia (spherical equivalent > or =-0.5) given a reduced uncorrected DVA at 16
      years was found. CONCLUSION: In this population, reduced uncorrected DVA in
      childhood is an inaccurate and inappropriate intermediate "phenotype" for
      capturing adult myopia status. However, our findings support assessment of DVA in
      secondary school children as an effective method of identifying refractive error
      (both myopia and hypermetropia).

PMID- 17020901
TI  - The use of the Newcastle Control Score in the management of intermittent
      exotropia.
AB  - AIM: To evaluate the use of the Newcastle Control Score (NCS) in the management
      of intermittent exotropia (X(T)). PARTICIPANTS AND METHODS: Children aged <11
      years with X(T) had an assessment of NCS as part of routine management. Other
      data collected included visual acuity, near and distance alignment with
      alternating prism cover test and near (Frisby test) and distance stereoacuity
      (Frisby Davis Distance Stereotest (FD2TM)). Analysis involved correlation between
      baseline NCS, angle and stereoacuity, examination of change over time and
      logistic regression to determine predictors of surgery. RESULTS: Baseline data
      were obtained on 272 children and follow-up data on 157. Mean (SD) age was 4
      (1.9) years. Complete NCSs were obtained for all except one child at baseline,
      and all children at follow-up. At baseline, total NCS and the home control
      component were correlated with near stereo (r = -0.22, p<0.01 and r = -0.19,
      p<0.02, respectively), near alignment (r = 0.34, p<0.001 and r = 0.19, p<0.02)
      and distance alignment (r = 0.30, p<0.001 and r = 0.26, p<0.001). The clinic near
      control component was correlated with near alignment (r = 0.39, p<0.001), but not
      near stereoacuity, and the clinic distance control with near alignment (r = 0.16,
      p<0.02), distance alignment (r = 0.27, p<0.001) and distance stereoacuity (r = 
      0.25, p<0.03). A high (poor) NCS (> or =4) at the latest follow-up predicted
      surgery (p<0.001, OR 29.3, 95% CI 6.2 to 138.7). CONCLUSION: The NCS is a useful
      measure of the clinical severity of X(T), can be used to serially assess
      improvement or deterioration and is a useful tool for the management of these
      patients.

PMID- 17020902
TI  - The suprabasal layer of corneal epithelial cells represents the major barrier
      site to the passive movement of small molecules and trafficking leukocytes.
AB  - AIMS: To investigate the site of barrier function to the passive diffusion of a
      small molecule (phalloidin) in the corneal epithelium in the mouse. METHODS:
      Penetration of phalloidin (molecular weight 1115 daltons) into the cornea was
      evaluated by studying fluorescent binding of phalloidin to actin in tissue
      sections, in whole mount preparations, and in the fixed intact globe by confocal
      microscopy. In addition, the location of tight junction proteins in the
      individual layers of the corneal epithelium was determined by
      immunohistochemistry. RESULTS: Phalloidin staining of corneal sections was
      positive in all corneal layers in tissue sections and in all layers of the
      corneal epithelium except the suprabasal layer in excised fixed whole mounts of
      the cornea. However, when phalloidin staining was attempted in intact fixed
      globes, before excision of the cornea for whole mount preparation, only the most
      superficial layer of cells was stained indicating that phalloidin could not
      penetrate the tissue beyond the suprabasal epithelial layer. Detergent (Triton X
      100) treatment of the excised cornea and the intact fixed globe, allowed
      penetration of phalloidin into the suprabasal epithelial layer. Tight junction
      proteins occludin, ZO-1 and claudin were present in most layers of the cornea but
      while ZO-1 and occludin were distributed in a typical pericellular pattern,
      claudin seemed to be particularly prominent in the suprabasal layer and appeared
      only as a discontinuous punctate pericellular pattern in the superficial layer.
      Intraepithelial leukocytes were detected in the superficial epithelium and the
      basal epithelium but not in the suprabasal epithelium. CONCLUSION: The suprabasal
      epithelium cell layer appears to represent the main barrier site to the passage
      of small molecules and cells in the mouse cornea and this property may be
      attributable to prominent claudin expression in this layer.

PMID- 17020903
TI  - Robotic ocular surgery.
AB  - BACKGROUND: Bimanual, three-dimensional robotic surgery has proved valuable for a
      variety of surgical procedures. AIMS: To examine the use of a commercially
      available surgical robot for ocular microsurgery. METHODS: Using a da Vinci
      surgical robot, ocular microsurgery was performed with repair of a corneal
      laceration in a porcine model. The experiments were performed on harvested
      porcine eyes placed in an anatomical position using a foam head on a standard
      operating room table. A video scope and two, 360 degrees -rotating, 8-mm, wrested
      end effector instruments were placed over the eye with three robotic arms. The
      surgeon performed the actual procedures while positioned at a robotic system
      console that was located across the operating room suite. Each surgeon placed
      three 10-0 sutures, and this was documented with still and video photography.
      RESULTS: Ocular microsurgery was successfully performed using the da Vinci
      surgical robot. The robotic system provided excellent visualisation, as well as
      controlled and delicate placement of the sutures at the corneal level.
      CONCLUSIONS: Robotic ocular microsurgery is technically feasible in the porcine
      model and warrants consideration for evaluation in controlled human trials to
      deploy functioning remote surgical centres in areas without access to state-of
      the-art surgical skill and technology.

PMID- 17020904
TI  - Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.
AB  - SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene
      identified for generalized epilepsy with febrile seizures plus (GEFS+). Only
      three families have been published with SCN1B mutations. Here, we present four
      new families with SCN1B mutations and characterize the associated phenotypes.
      Analysis of SCN1B was performed on 402 individuals with various epilepsy
      syndromes. Four probands with missense mutations were identified. Detailed
      electroclinical phenotyping was performed on all available affected family
      members including quantitative MR imaging in those with temporal lobe epilepsy
      (TLE). Two new families with the original C121W SCN1B mutation were identified;
      novel mutations R85C and R85H were each found in one family. The following
      phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile
      seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two
      unclassified and ten unaffected individuals. All individuals with confirmed TLE
      had the C121W mutation; two underwent temporal lobectomy (one with hippocampal
      sclerosis and one without) and both are seizure free. We confirm the role of
      SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with
      an SCN1B mutation is not a contraindication to epilepsy surgery.

PMID- 17020905
TI  - Molecular characterization of human adenomyosis.
AB  - Adenomyosis is a common gynaecological disorder characterized by the abnormal
      growth of endometrium into the myometrium and myometrial hypertrophy/hyperplasia.
      Uterine fibroids are benign neoplasms of the myometrium, and they represent a
      diagnostic pitfall for adenomyosis. In this study, we have used the genome-wide
      Affymetrix U133 Plus 2.0 microarray platform to compare the gene expression
      patterns of adenomyosis, uterine fibroids, normal endometrium and myometrium.
      Unsupervised principal component analysis (PCA) revealed that these four tissue
      types could be segregated from one another solely based on their gene expression
      profiles. Analysis of variance (ANOVA), followed by Tukey means separation test,
      significance analysis of microarrays (SAM) and 2-fold change threshold,
      identified 7415 probe sets as differentially expressed among the four groups of
      samples. Supervised cluster analysis based on these probe sets clustered
      adenomyosis most closely with endometrium and uterine fibroids with myometrium,
      consistent with the anatomic origin of these two diseases. The Tukey means
      separation post hoc testing found 2073 probe sets altered between adenomyosis and
      normal endometrium or myometrium, and 2327 probe sets altered in expression when
      comparing uterine fibroids with myometrium. Using Ingenuity Pathways Analysis
      (IPA), we found 9 highly significant functional networks in adenomyosis and 10 in
      uterine fibroids. Notably, the top network in both cases was associated with
      functions implicated in cancer and cell death. Finally, we compared the gene
      expression profiles of adenomyosis and uterine fibroids and identified 471
      differentially expressed probe sets that may represent potential biomarkers for
      the differential diagnosis of these diseases.

PMID- 17020906
TI  - Deficient expression of monoamine oxidase A in the endometrium is associated with
      implantation failure in women participating as recipients in oocyte donation.
AB  - Successful implantation depends both on the quality of the embryo and on the
      endometrial receptivity. The latter depends on progesterone-induced changes in
      gene expression, a process that has been characterized by microarray analysis.
      One of the genes whose transcription appears to be enhanced during the receptive
      period is monoamine oxidase A (MAO-A). Our first objective was to confirm the
      increased expression of MAO-A in the endometrium during the receptive phase of
      spontaneous normal cycles using real time PCR and immunofluorescence. The second
      objective was to examine the endometrial expression of MAO-A during the receptive
      phase induced by exogenous estradiol (E(2)) and progesterone in patients whose
      endometrium was shown to have been either receptive or non-receptive to embryo
      implantation in repeated cycles of oocyte donation. Results showed that MAO-A
      transcript levels increased between the pre-receptive (LH+3) and receptive phase
      (LH+7) in all spontaneous cycles examined, with a median increase of 25-fold.
      Immunofluorescent labelling demonstrated MAO-A localization to the glandular and
      luminal epithelium with an increasing positive score between LH+3 and LH+7.
      Conversely, prior failure of embryo implantation was associated with a 29-fold
      decrease in MAO-A mRNA levels and a substantial reduction in MAO-A protein
      immunofluorescent label score. These results show a strong association between
      endometrial receptivity and MAO-A expression in the endometrial epithelium,
      suggesting an important role for this enzyme in normal implantation.

PMID- 17020907
TI  - Factor XII autoantibodies as a novel marker for thrombosis and adverse obstetric
      history in patients with systemic lupus erythematosus.
AB  - AIM: To investigate the clinical significance of anti-factor XII (FXII) in a
      large cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND
      METHODS: This study comprised 127 patients with SLE. IgG and IgM anti-FXII were
      tested by an in-house ELISA. 123 healthy donors comprised the control group.
      RESULTS: 51 (40%) patients with SLE and 9 (7%) healthy controls were positive for
      anti-FXII. IgG and IgM anti-FXII were frequently found in patients with
      thrombosis (28% and 13%, respectively). Levels of IgG and IgM anti-FXII were
      higher in patients with thrombosis than in the control group (p<0.001 and
      p=0.005, respectively). Anti-FXII was more frequent in patients with arterial
      thrombosis (31% vs 4% for IgG and 14% vs 3% for IgM, respectively) and venous
      thrombosis than in controls (37% vs 4% for IgG). IgG anti-FXII were more frequent
      in patients with miscarriages and fetal death (35% and 40% vs 4% for IgM). The
      prevalence of IgM anti-FXII was not different between groups. CONCLUSION: Anti
      FXII are frequent in patients with SLE. Their presence is associated with
      thrombosis and adverse obstetric history, making these antibodies a novel marker
      for the antiphospholipid syndrome.

PMID- 17020908
TI  - GM-CSF neutralisation suppresses inflammation and protects cartilage in acute
      streptococcal cell wall arthritis of mice.
AB  - OBJECTIVE: The pathogenic involvement of granulocyte-macrophage colony
      stimulating factor (GM-CSF) in arthritis has been put forward. We have
      investigated the therapeutic effect of GM-CSF neutralisation in the streptococcal
      cell wall (SCW) arthritis model in mice. In this model, the pathogenic
      contribution of tumour necrosis factor (TNF)alpha is minor and is expressed only
      on joint swelling, whereas cartilage proteoglycan depletion is independent of
      this cytokine. METHODS: Acute monarthritis was induced by injection of SCW
      bacterial extracts to mouse knees. Treatments (mAb 22E9 at 300, 100, 30 microg;
      or Enbrel 300 microg) were given twice intraperitoneally 2 h before and 3 days
      after disease induction. Swelling was assessed by (99m)Tc uptake into knees on
      days 1 and 2. Local cytokine levels were determined in patellae washouts on day
      one. Proteoglycan loss from cartilage was scored on histological sections at
      termination on day four. RESULTS: Treatment with anti-GM-CSF mAb 22E9 showed a
      dose-related efficacy by decreasing swelling that was significant at the 300 and
      100 microg doses in comparison to isotype control, and comparable to
      dexamethasone (5 mg/ml). Proteoglycan loss from cartilage was also significantly
      reduced by mAb 22E9 300 microg (p=0.001). This reduced proteoglycan loss observed
      after GM-CSF neutralisation was not seen after TNFalpha-blockade with Enbrel.
      Similarly, levels of interleukin 1beta in joints were reduced after treatment
      with 22E9 mAb (p=0.003) but not in mice receiving Enbrel. CONCLUSIONS: Our
      findings show a pathogenic role for GM-CSF in this arthritis model, support the
      therapeutic potential of neutralising this cytokine, and may indicate therapeutic
      activity of an anti-GM-CSF mAb in TNFalpha-independent disease situations.

PMID- 17020909
TI  - Cardiac overexpression of metallothionein rescues chronic alcohol intake-induced
      cardiomyocyte dysfunction: role of Akt, mammalian target of rapamycin and
      ribosomal p70s6 kinase.
AB  - AIMS: Reduced insulin sensitivity following alcohol intake plays a role in
      alcohol-induced organ damage although its precise mechanism is undefined. This
      study was designed to examine the effect of cardiac overexpression of the
      antioxidant metallothionein on alcohol-induced cardiac contractile dysfunction
      and post-receptor insulin signaling. METHODS: FVB and metallothionein mice were
      fed a 4% alcohol diet for 16 weeks. Cardiomyocyte contractile function was
      evaluated including peak shortening (PS), time-to-PS (TPS), and time-to
      relengthening (TR(90)). Post-insulin receptor signaling molecules Akt, mammalian
      target of rapamycin (mTOR), and ribosomal p70s6 kinase (p70s6k) were evaluated
      using western blot analysis. Akt1 kinase activity was assayed with a
      phosphotransferase kit. RESULTS: Alcohol intake dampened whole body glucose
      tolerance, depressed PS, shortened TPS, and prolonged TR(90), which were
      abrogated by metallothionein with the exception of glucose intolerance. Our
      results revealed reduced expression of total Akt, phosphorylated mTOR, and
      phosphorylated p70s6k-to-p70s6k ratio as well as Akt1 kinase activity in alcohol
      consuming FVB mice. Phosphorylated Akt, total mTOR, and phosphorylated p70s6k
      were unaffected by alcohol. Metallothionein ablated reduced Akt protein and
      kinase activity without affecting any other proteins or their phosphorylation.
      CONCLUSION: In summary, our data suggest that chronic alcohol intake interrupted
      cardiac contractile function and Akt/mTOR/p70s6k signaling. Akt but unlikely mTOR
      and p70s6k may contribute to metallothionein-elicited cardiac protective
      response.

PMID- 17020910
TI  - Diazepam dose-dependently increases or decreases implicit priming of alcohol
      associations in problem drinkers.
AB  - AIMS: Words denoting negative affect (NEG) have been found to prime alcohol
      related words (ALC) on semantic priming tasks, and this effect is tied to
      severity of addiction. Previous research suggested that high doses of
      benzodiazepines may dampen NEG-ALC priming. The present study tested this
      possibility and the role of motivation for alcohol in this process. METHODS: A
      placebo-controlled, double blind, between-within, counterbalanced design was
      employed. Two groups of male problem drinkers (n = 6/group) received a high (15
      mg) or low (5-mg) dose of diazepam versus placebo on two identical test sessions.
      A lexical decision task assessed priming. RESULTS: Under placebo, significant NEG
      ->ALC priming emerged in each group. High-dose diazepam selectively reversed this
      effect, while low-dose selectively enhanced it. Correlations between NEG-->ALC
      priming and desire for alcohol provided further support that semantic priming of
      ALC concepts reflects a motivational process. The bi-directional effects found
      here parallel the effects of high- versus low-dose benzodiazepines on alcohol
      self-administration in animals. CONCLUSIONS: High-dose diazepam reduces prime
      induced activation of ALC concepts in problem drinkers. Low-dose diazepam
      facilitates this process, and cross-priming of motivation for alcohol appears to
      explain this effect. Neurochemical modulation of the alcohol memory network may
      contribute to the motivational effects of benzodiazepines in problem drinkers.

PMID- 17020911
TI  - Effect of breast feeding on intelligence in children: prospective study, sibling
      pairs analysis, and meta-analysis.
AB  - OBJECTIVE: To assess the importance of maternal intelligence, and the effect of
      controlling for it and other important confounders, in the link between breast
      feeding and children's intelligence. DESIGN: Examination of the effect of breast
      feeding on cognitive ability and the impact of a range of potential confounders,
      in particular maternal IQ, within a national database. Additional analyses
      compared pairs of siblings from the sample who were and were not breast fed. The
      results are considered in the context of other studies that have also controlled
      for parental intelligence via meta-analysis. SETTING: 1979 US national
      longitudinal survey of youth. SUBJECTS: Data on 5475 children, the offspring of
      3161 mothers in the longitudinal survey. MAIN OUTCOME MEASURE: IQ in children
      measured by Peabody individual achievement test. RESULTS: The mother's IQ was
      more highly predictive of breastfeeding status than were her race, education,
      age, poverty status, smoking, the home environment, or the child's birth weight
      or birth order. One standard deviation advantage in maternal IQ more than doubled
      the odds of breast feeding. Before adjustment, breast feeding was associated with
      an increase of around 4 points in mental ability. Adjustment for maternal
      intelligence accounted for most of this effect. When fully adjusted for a range
      of relevant confounders, the effect was small (0.52) and non-significant (95%
      confidence interval -0.19 to 1.23). The results of the sibling comparisons and
      meta-analysis corroborated these findings. CONCLUSIONS: Breast feeding has little
      or no effect on intelligence in children. While breast feeding has many
      advantages for the child and mother, enhancement of the child's intelligence is
      unlikely to be among them.

PMID- 17020912
TI  - Dosimetric properties of new cards with high-sensitivity MCP-N (LiF:Mg,Cu,P)
      detectors for Harshaw automatic reader.
AB  - A new configuration for a thermoluminescent dosimetric card has been developed
      through collaboration between the Institute of Nuclear Physics in Krakow and
      several commercial dosimetric companies. The card is based on high-sensitivity
      LiF:Mg,Cu,P circular pellets (MCP-N) welded inside synthetic foils. The basic
      configuration consists of two pellets of 3.6 mm diameter and thicknesses from
      0.25 up to 0.38 mm. The cards can be processed in a standard 6600 or 8800 Harshaw
      automatic TLD reader. The dosemeters demonstrate very high sensitivity, low
      background and good stability. This article presents results of the performance
      tests of the new dosimetric cards in the automatic TLD readers and a comparison
      of their properties.

PMID- 17020913
TI  - Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by
      affecting its DNA-binding.
AB  - Glutamate racemase (MurI) catalyses the conversion of l-glutamate to d-glutamate,
      an important component of the bacterial cell wall. MurI from Escherichia coli
      inhibits DNA gyrase in presence of the peptidoglycan precursor. Amongst the two
      glutamate racemases found in Bacillus subtilis, only one inhibits gyrase, in
      absence of the precursor. Mycobacterium tuberculosis has a single gene encoding
      glutamate racemase. Action of M.tuberculosis MurI on DNA gyrase activity has been
      examined and its mode of action elucidated. We demonstrate that mycobacterial
      MurI inhibits DNA gyrase activity, in addition to its precursor independent
      racemization function. The inhibition is not species-specific as E.coli gyrase is
      also inhibited but is enzyme-specific as topoisomerase I activity remains
      unaltered. The mechanism of inhibition is different from other well-known gyrase
      inhibitors. MurI binds to GyrA subunit of the enzyme leading to a decrease in DNA
      binding of the holoenzyme. The sequestration of the gyrase by MurI results in
      inhibition of all reactions catalysed by DNA gyrase. MurI is thus not a typical
      potent inhibitor of DNA gyrase and instead its role could be in modulation of the
      gyrase activity.

PMID- 17020914
TI  - PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing
      its retention in the nucleus.
AB  - Progesterone receptor (PR) plays a critical role in cell proliferation and
      differentiation, and its transcriptional activity is known to be modulated by
      cofactor proteins. In the present study, we demonstrated that in the presence of
      progesterone, protein inhibitor of activated STAT-3 (PIAS3) significantly
      inhibited the PR transcriptional activity and the expression of progesterone
      responsive genes. Reduction of endogenous PIAS3 by PIAS3 small-interfering RNA
      enhanced PR transactivation in a ligand-dependent manner. PIAS3 interacted with
      PR both in vitro and in vivo and the interaction was enhanced by progesterone.
      Furthermore, our findings suggested that PIAS3 strongly induced PRB sumoylation
      at three sites, Lys-7, Lys-388 and Lys-531. In addition, novel roles in PRB
      nuclear retention and transactivation were identified for these sites. Our data
      also suggested that PIAS3 was recruited in a largely hormone-dependent manner in
      response to a progesterone-responsive promoter. Finally, we demonstrated that
      PIAS3 inhibited the DNA-binding activity of PR and influenced its nuclear export
      as well as PR transactivation. Taken together, these data strongly suggested that
      PIAS3 played an important physiological role in PR function.

PMID- 17020915
TI  - Purification of the yeast Slx5-Slx8 protein complex and characterization of its
      DNA-binding activity.
AB  - SLX5 and SLX8 encode RING-finger proteins that were previously identified based
      on their requirement for viability in yeast cells lacking Sgs1 DNA helicase. Slx5
      and Slx8 proteins are known to be required for genome stability and to physically
      interact in yeast extracts; however, their biochemical functions are unknown. To
      address this question we purified and characterized recombinant Slx5 and Slx8
      proteins. Here we show that Slx5 and Slx8 form a heterodimeric complex with
      double-stranded DNA (dsDNA)-binding activity. Individually, only the Slx8 subunit
      displays this activity. Structure-function studies indicate that the DNA-binding
      activity requires only the N-terminal 160 amino acids of Slx8, but not its C
      terminal RING-finger domain. Alleles of SLX8 that express the RING-finger domain
      alone show almost complete complementation in yeast indicating that this DNA
      binding domain is not essential for this in vivo function. Consistent with these
      findings we show that Slx5 immunolocalizes to the nucleus and that a portion of
      the Slx8 protein co-fractionates with chromatin. These results suggest that Slx5
      Slx8 may act directly on DNA to promote genome stability.

PMID- 17020916
TI  - Assessing incomplete deprotection of microarray oligonucleotides in situ.
AB  - En masse analysis of gene structure and function by array technologies will have
      a lasting and profound effect on biology and medicine. This impact can be
      compromised by low quality of probes within arrays, which we show can be caused
      by incomplete removal of chemical protecting groups. To solve this quality
      control problem, we present a sensitive, specific and facile method to detect
      these groups in situ on arrays using monoclonal antibodies and existing
      instrumentation. Screening of microarrays with these monoclonal antibodies should
      guide the consideration given to data derived from these and should enhance the
      accuracy of the results obtained.

PMID- 17020917
TI  - Multiple signaling pathways regulate the transcriptional activity of the orphan
      nuclear receptor NURR1.
AB  - The orphan nuclear receptor nurr1 (NR4A2) is an essential transcription factor
      for the acquisition and maintenance of the phenotype of dopamine (DA)
      synthesizing neurons in the mesencephalon. Although structurally related to
      ligand-regulated nuclear receptors, nurr1 is functionally atypical due to its
      inability to bind a cognate ligand and to activate transcription following
      canonical nuclear receptor (NR) rules. Importantly, the physiological stimuli
      that activate this NR and the signaling proteins that regulate its
      transcriptional activity in mesencephalic neurons are unknown. We used an
      affinity chromatography approach and CSM14.1 cells of mesencephalic origin to
      isolate and identify several proteins that interact directly with nurr1 and
      regulate its transcriptional activity. Notably, we demonstrate that the mitogen
      activated protein kinases, ERK2 and ERK5, elevate, whereas LIM Kinase 1 inhibits
      nurr1 transcriptional activity. Furthermore, nurr1 recruits ERK5 to a NBRE
      containing promoter and is a potential substrate for this kinase. We have
      identified amino acids in the A/B domain of nurr1 important for mediating the
      ERK5 activating effects on nurr1 transcriptional activity. Our results suggest
      that nurr1 acts as a point of convergence for multiple signaling pathways that
      likely play a critical role in differentiation and phenotypic expression of
      dopaminergic (DAergic) neurons.

PMID- 17020918
TI  - Human sat III and Drosophila hsr omega transcripts: a common paradigm for
      regulation of nuclear RNA processing in stressed cells.
AB  - Exposure of cells to stressful conditions elicits a highly conserved defense
      mechanism termed the heat shock response, resulting in the production of
      specialized proteins which protect the cells against the deleterious effects of
      stress. The heat shock response involves not only a widespread inhibition of the
      ongoing transcription and activation of heat shock genes, but also important
      changes in post-transcriptional processing. In particular, a blockade in splicing
      and other post-transcriptional processing has been described following stress in
      different organisms, together with an altered spatial distribution of the
      proteins involved in these activities. However, the specific mechanisms that
      regulate these activities under conditions of stress are little understood. Non
      coding RNA molecules are increasingly known to be involved in the regulation of
      various activities in the cell, ranging from chromatin structure to splicing and
      RNA degradation. In this review, we consider two non-coding RNAs, the hsr(omega)
      transcripts in Drosophila and the sat III transcripts in human cells, that seem
      to be involved in the dynamics of RNA-processing factors in normal and/or
      stressed cells, and thus provide new paradigms for understanding transcriptional
      and post-transcriptional regulations in normal and stressed cells.

PMID- 17020919
TI  - Identification of multiple transcription initiation, polyadenylation, and splice
      sites in the Drosophila melanogaster TART family of telomeric retrotransposons.
AB  - The Drosophila non-long terminal repeat (non-LTR) retrotransposons TART and HeT-A
      specifically retrotranspose to chromosome ends to maintain Drosophila telomeric
      DNA. Relatively little is known, though, about the regulation of their expression
      and their retrotransposition to telomeres. We have used rapid amplification of
      cDNA ends (RACE) to identify multiple transcription initiation and
      polyadenylation sites for sense and antisense transcripts of three subfamilies of
      TART elements in Drosophila melanogaster. These results are consistent with the
      production of an array of TART transcripts. In contrast to other Drosophila non
      LTR elements, a major initiation site for sense transcripts was mapped near the
      3' end of the TART 5'-untranslated region (5'-UTR), rather than at the start of
      the 5'-UTR. A sequence overlapping this sense start site contains a good match to
      an initiator consensus for the transcription start sites of Drosophila LTR
      retrotransposons. Interestingly, analysis of 5' RACE products for antisense
      transcripts and the GenBank EST database revealed that TART antisense transcripts
      contain multiple introns. Our results highlight differences between transcription
      of TART and of other Drosophila non-LTR elements and they provide a foundation
      for testing the relationship between exceptional aspects of TART transcription
      and TART's specialized role at telomeres.

PMID- 17020920
TI  - Analysis of protein sequence and interaction data for candidate disease gene
      prediction.
AB  - Linkage analysis is a successful procedure to associate diseases with specific
      genomic regions. These regions are often large, containing hundreds of genes,
      which make experimental methods employed to identify the disease gene arduous and
      expensive. We present two methods to prioritize candidates for further
      experimental study: Common Pathway Scanning (CPS) and Common Module Profiling
      (CMP). CPS is based on the assumption that common phenotypes are associated with
      dysfunction in proteins that participate in the same complex or pathway. CPS
      applies network data derived from protein-protein interaction (PPI) and pathway
      databases to identify relationships between genes. CMP identifies likely
      candidates using a domain-dependent sequence similarity approach, based on the
      hypothesis that disruption of genes of similar function will lead to the same
      phenotype. Both algorithms use two forms of input data: known disease genes or
      multiple disease loci. When using known disease genes as input, our combined
      methods have a sensitivity of 0.52 and a specificity of 0.97 and reduce the
      candidate list by 13-fold. Using multiple loci, our methods successfully identify
      disease genes for all benchmark diseases with a sensitivity of 0.84 and a
      specificity of 0.63. Our combined approach prioritizes good candidates and will
      accelerate the disease gene discovery process.

PMID- 17020921
TI  - Alu elements as regulators of gene expression.
AB  - Alu elements are the most abundant repetitive elements in the human genome; they
      emerged 65 million years ago from a 5' to 3' fusion of the 7SL RNA gene and
      amplified throughout the human genome by retrotransposition to reach the present
      number of more than one million copies. Over the last years, several lines of
      evidence demonstrated that these elements modulate gene expression at the post
      transcriptional level in at least three independent manners. They have been shown
      to be involved in alternative splicing, RNA editing and translation regulation.
      These findings highlight how the genome adapted to these repetitive elements by
      assigning them important functions in regulation of gene expression. Alu elements
      should therefore be considered as a large reservoir of potential regulatory
      functions that have been actively participating in primate evolution.

PMID- 17020922
TI  - Controlling bacteriophage phi29 DNA-packaging motor by addition or discharge of a
      peptide at N-terminus of connector protein that interacts with pRNA.
AB  - Bacteriophage phi29 utilizes a motor to translocate genomic DNA into a preformed
      procapsid. The motor contains six pRNAs, an enzyme and one 12-subunit connector
      with a central channel for DNA transportation. A 20-residue peptide containing a
      His-tag was fused to the N-terminus of the connector protein gp10. This fusion
      neither interfered with procapsid assembly nor affected the morphology of the
      prolate-shaped procapsid. However, the pRNA binding and virion assembly activity
      were greatly reduced. Such decreased functions can be switched back on by the
      removal of the tag via protease cleavage, supporting the previous finding that
      the N-terminus of gp10 is essential for the pRNA binding. The DNA-packaging
      efficiency with dimeric pRNA was more seriously affected by the extension than
      with monomeric pRNA. It is speculated that the fusion of the tag generated
      physical hindrance to pRNA binding, with greater influence for the dimers than
      the monomers due to their size. These results reveal a potential to turn off and
      turn on the motor by attaching or removing, respectively, a component to outer
      part of the motor, and offers an approach for the inhibition of viral replication
      by using a drug or a small peptide targeted to motor components.

PMID- 17020923
TI  - Using DNA pools for genotyping trios.
AB  - The genotyping of mother-father-child trios is a very useful tool in disease
      association studies, as trios eliminate population stratification effects and
      increase the accuracy of haplotype inference. Unfortunately, the use of trios for
      association studies may reduce power, since it requires the genotyping of three
      individuals where only four independent haplotypes are involved. We describe here
      a method for genotyping a trio using two DNA pools, thus reducing the cost of
      genotyping trios to that of genotyping two individuals. Furthermore, we present
      extensions to the method that exploit the linkage disequilibrium structure to
      compensate for missing data and genotyping errors. We evaluated our method on
      trios from CEPH pedigree 66 of the Coriell Institute. We demonstrate that the
      error rates in the genotype calls of the proposed protocol are comparable to
      those of standard genotyping techniques, although the cost is reduced
      considerably. The approach described is generic and it can be applied to any
      genotyping platform that achieves a reasonable precision of allele frequency
      estimates from pools of two individuals. Using this approach, future trio-based
      association studies may be able to increase the sample size by 50% for the same
      cost and thereby increase the power to detect associations.

PMID- 17020924
TI  - Structural analysis of aligned RNAs.
AB  - The knowledge about classes of non-coding RNAs (ncRNAs) is growing very fast and
      it is mainly the structure which is the common characteristic property shared by
      members of the same class. For correct characterization of such classes it is
      therefore of great importance to analyse the structural features in great detail.
      In this manuscript I present RNAlishapes which combines various secondary
      structure analysis methods, such as suboptimal folding and shape abstraction,
      with a comparative approach known as RNA alignment folding. RNAlishapes makes use
      of an extended thermodynamic model and covariance scoring, which allows to reward
      covariation of paired bases. Applying the algorithm to a set of bacterial trp
      operon leaders using shape abstraction it was able to identify the two
      alternating conformations of this attenuator. Besides providing in-depth analysis
      methods for aligned RNAs, the tool also shows a fairly well prediction accuracy.
      Therefore, RNAlishapes provides the community with a powerful tool for structural
      analysis of classes of RNAs and is also a reasonable method for consensus
      structure prediction based on sequence alignments. RNAlishapes is available for
      online use and download at http://rna.cyanolab.de.

PMID- 17020925
TI  - The Arabidopsis SUVR4 protein is a nucleolar histone methyltransferase with
      preference for monomethylated H3K9.
AB  - Proteins containing the evolutionarily conserved SET domain are involved in
      regulation of eukaryotic gene expression and chromatin structure through their
      histone lysine methyltransferase (HMTase) activity. The Drosophila SU(VAR)3-9
      protein and related proteins of other organisms have been associated with gene
      repression and heterochromatinization. In Arabidopsis there are 10 SUVH and 5
      SUVR genes encoding proteins similar to SU(VAR)3-9, and 4 SUVH proteins have been
      shown to control heterochromatic silencing by its HMTase activity and by
      directing DNA methylation. The SUVR proteins differ from the SUVH proteins in
      their domain structure, and we show that the closely related SUVR1, SUVR2 and
      SUVR4 proteins contain a novel domain at their N-terminus, and a SUVR specific
      region preceding the SET domain. Green fluorescent protein (GFP)-fusions of these
      SUVR proteins preferably localize to the nucleolus, suggesting involvement in
      regulation of rRNA expression, in contrast to other SET-domain proteins studied
      so far. A novel HMTase specificity was demonstrated for SUVR4, in that
      monomethylated histone H3K9 is its preferred substrate in vitro.

PMID- 17020927
TI  - Systemic NO production during (septic) shock depends on parenchymal and not on
      hematopoietic cells: in vivo iNOS expression pattern in (septic) shock.
AB  - Septic shock is the leading cause of death in noncoronary intensive care units
      and the 10th leading cause of death overall. Several lines of evidence support an
      important role for the vasodilator NO in hypotension, a hallmark of septic shock.
      However, NO may also positively or negatively regulate inflammation, apoptosis,
      and oxidative stress. These dual effects of NO may relate to its isoform specific
      production but also to differences in cellular and/or temporal expression. Via
      bone marrow transplantations, we examined the contribution of hematopoietic cells
      to the dramatically elevated NO levels seen in (septic) shock. Surprisingly,
      hematopoietic cells are not responsible at all for the production of circulating
      NO after systemic tumor necrosis factor or lipopolysaccharide challenge and
      contribute only marginally in a bacteremic (Salmonella) model of septic shock.
      Immunohistochemistry identified the nonhematopoietic sources of NO as
      hepatocytes, paneth cells, and intestinal and renal epithelial cells. In
      contrast, during granulomatous Bacillus Calmette-Guerin inflammation, the
      hematopoietic cell population represents the sole source of systemic NO. These
      mouse data demonstrate that, in contrast to the general conjecture, the
      dramatically elevated levels of NO during (septic) shock are not produced by
      hematopoietic cells such as monocytes/macrophages but rather by parenchymal cells
      in liver, kidney and gut.

PMID- 17020926
TI  - Quantitative analysis of the oxidative DNA lesion, 2,2-diamino-4-(2-deoxy-beta-D
      erythro-pentofuranosyl)amino]-5(2H)-oxazolone (oxazolone), in vitro and in vivo
      by isotope dilution-capillary HPLC-ESI-MS/MS.
AB  - A major DNA oxidation product, 2,2-diamino-4-[(2-deoxy-beta-D-erythro
      pentofuranosyl)amino]-5(2H)-oxazolone (oxazolone), can be generated either
      directly by oxidation of dG or as a secondary oxidation product with an
      intermediate of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). Site-specific
      mutagenesis studies indicate that oxazolone is a strongly mispairing lesion,
      inducing approximately 10-fold more mutations than 8-oxo-dG. While 8-oxo-dG
      undergoes facile further oxidation, oxazolone appears to be a stable final
      product of guanine oxidation, and, if formed in vivo, can potentially serve as a
      biomarker of DNA damage induced by oxidative stress. In this study, capillary
      liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI
      MS/MS) methods were developed to enable quantitative analysis of both 8-oxo-dG
      and oxazolone in DNA from biological sources. Sensitive and specific detection of
      8-oxo-dG and oxazolone in enzymatic DNA hydrolysates was achieved by isotope
      dilution with the corresponding 15N-labeled internal standards. Both nucleobase
      adducts were formed in a dose-dependent manner in calf thymus DNA subjected to
      photooxidation in the presence of riboflavin. While the amounts of oxazolone
      continued to increase with the duration of irradiation, those of 8-oxo-dG reached
      a maximum at 20 min, suggesting that 8-oxo-dG is converted to secondary oxidation
      products. Both lesions were found in rat liver DNA isolated under carefully
      monitored conditions to minimize artifactual oxidation. Liver DNA of diabetic and
      control rats maintained on a diet high in animal fat contained 2-6 molecules of
      oxazolone per 10(7) guanines, while 8-oxo-dG amounts in the same samples were
      between 3 and 8 adducts per 10(6) guanines. The formation of oxazolone lesions in
      rat liver DNA, their relative stability in the presence of oxidants and their
      potent mispairing characteristics suggest that oxazolone may play a role in
      oxidative stress-mediated mutagenesis.

PMID- 17020928
TI  - Pneumocystis-mediated IL-8 release by macrophages requires coexpression of
      mannose receptors and TLR2.
AB  - Interaction with the unique fungus Pneumocystis (Pc) promotes IL-8 release by
      human alveolar macrophages (AM), although the receptor(s) mediating IL-8 release
      have not been identified. TLR2 recognizes fungal components and mediates release
      of host defense cytokines and chemokines, although whether TLR2 mediates
      signaling in response to Pc is not known. In the current study, Pc induced IL-8
      release by human AM, and AM pretreatment with anti-TLR2 neutralizing antibody
      reduced IL-8 release. However, in nonphagocytic human embryonic kidney (HEK)293
      cells transfected with human TLR2 cDNA, incubation with Pc did not induce IL-8
      release, whereas these same cells released IL-8 in response to the TLR2 agonist
      lipoteichoic acid. Targeted gene silencing of AM mannose receptors (MR;
      phagocytic receptors for Pc) using small interfering RNA also reduced Pc-mediated
      IL-8 release in human AM. However, HEK293 cells transfected with human MR cDNA
      alone did not release IL-8 in response to Pc. In contrast, HEK293 cells
      cotransfected with human TLR2 and human MR cDNA released IL-8 in response to Pc.
      In human AM, Pc promoted direct interaction of MR and TLR2, IL-8 release was
      reduced markedly upon simultaneous blocking of TLR2 and gene silencing of MR, and
      IL-8 release was dependent in part on transcription factor NF-kappaB and ERK1/2
      and JNK MAPKs. These studies demonstrate that Pc-mediated IL-8 release by human
      AM requires the coexpression of MR and TLR2 and further supports the concept that
      combinatorial interactions of macrophage innate receptors provide specificity of
      host defense cell responses to infectious challenge.

PMID- 17020929
TI  - The disconnect between animal models of sepsis and human sepsis.
AB  - Frequently used experimental models of sepsis include cecal ligation and
      puncture, ascending colon stent peritonitis, and the i.p. or i.v. injection of
      bacteria or bacterial products (such as LPS). Many of these models mimic the
      pathophysiology of human sepsis. However, identification of mediators in animals,
      the blockade of which has been protective, has not translated into clinical
      efficacy in septic humans. We describe the shortcomings of the animal models and
      reasons why effective therapy for human sepsis cannot be derived readily from
      promising findings in animal sepsis.

PMID- 17020930
TI  - Human rhinovirus induces robust IP-10 release by monocytic cells, which is
      independent of viral replication but linked to type I interferon receptor
      ligation and STAT1 activation.
AB  - Human rhinovirus (HRV)-induced respiratory infections are associated with
      elevated levels of IFN-gamma-inducible protein 10 (IP-10), which is an enhancer
      of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte
      number. Increased IP-10 expression is exhibited by airway epithelial cells
      following ex vivo HRV challenge and requires intracellular viral replication;
      however, there are conflicting reports regarding the necessity of type I IFN
      receptor ligation for IP-10 expression. Furthermore, the involvement of resident
      airway immune cells, predominantly bronchoalveolar macrophages, in contributing
      to HRV-stimulated IP-10 elaboration remains unclear. In this regard, our findings
      demonstrate that ex vivo exposure of human peripheral blood monocytes and
      bronchoalveolar macrophages (monocytic cells) to native or replication-defective
      HRV serotype 16 (HRV16) resulted in similarly robust levels of IP-10 release,
      which occurred in a time- and dose-dependent manner. Furthermore, HRV16 induced a
      significant increase in type I IFN (IFN-alpha) release and STAT1 phosphorylation
      in monocytes. Neutralization of the type I IFN receptor and inhibition of JAK or
      p38 kinase activity strongly attenuated HRV16-stimulated STAT1 phosphorylation
      and IP-10 release. Thus, this work supports a model, wherein HRV16-induced IP-10
      release by monocytic cells is modulated via autocrine/paracrine action of type I
      IFNs and subsequent JAK/STAT pathway activity. Our findings demonstrating robust
      activation of monocytic cells in response to native and/or replication-defective
      HRV16 challenge represent the first evidence indicating a mechanistic disparity
      in the activation of macrophages when compared with epithelial cells and suggest
      that macrophages likely contribute to cytokine elaboration following HRV
      challenge in vivo.

PMID- 17020931
TI  - Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex
      activities in cultured vascular endothelial cells.
AB  - There is evidence that nitric oxide (NO), superoxide (O(2)(*-)), and their
      associated reactive nitrogen species (RNS) produced by vascular endothelial cells
      (ECs) in response to hemodynamic forces play a role in cell signaling. NO is
      known to impair mitochondrial respiration. We sought to determine whether
      exposure of human umbilical vein ECs (HUVECs) to steady laminar shear stress and
      the resultant NO production modulate electron transport chain (ETC) enzymatic
      activities. The activities of respiratory complexes I, II/III, and IV were
      dependent on the presence of serum and growth factor supplement in the medium. EC
      exposure to steady laminar shear stress (10 dyn/cm(2)) resulted in a gradual
      inhibition of each of the complexes starting as early as 5 min from the flow
      onset and lasting up to 16 h. Ramp flow resulted in inhibition of the complexes
      similar to that of step flow. When ECs were sheared in the presence of the NO
      synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM), the
      NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c
      PTIO; 100 microM), or the peroxynitrite (ONOO(-)) scavenger uric acid (UA; 50
      microM), the flow-inhibitory effect on mitochondrial complexes was attenuated. In
      particular, L-NAME and UA abolished the flow effect on complex IV. Increased
      tyrosine nitration was observed in the mitochondria of sheared ECs, and UA
      blocked the shear-induced nitrotyrosine staining. In summary, shear stress
      induces mitochondrial RNS formation that inhibits the electron flux of the ETC at
      multiple sites. This may be a critical mechanism by which shear stress modulates
      EC signaling and function.

PMID- 17020932
TI  - High-throughput assays of phagocytosis, phagosome maturation, and bacterial
      invasion.
AB  - Ingestion of foreign particles by macrophages and neutrophils and the fate of the
      vacuole that contains the ingested material are generally monitored by optical
      microscopy. Invasion of host cells by pathogenic bacteria and their intracellular
      proliferation are similarly studied by microscopy or by plating assays. These
      labor-intensive and time-consuming methods limit the number of assays that can be
      performed. The effort required to test multiple reagents or conditions can be
      prohibitive. We describe high-throughput assays of phagocytosis and of phagosomal
      maturation. An automated fluorescence microscope-based platform and associated
      analysis software were used to study Fcgamma receptor-mediated phagocytosis of
      IgG-opsonized particles by cultured murine macrophages. Phagosomal acidification
      was measured as an index of maturation. The same platform was similarly used to
      implement high-throughput assays of invasion of mammalian cells by pathogenic
      bacteria. The invasion of HeLa cells by Salmonella and the subsequent
      intracellular proliferation of the bacteria were measured rapidly and reliably in
      large populations of cells. These high-throughput methods are ideally suited for
      the efficient screening of chemical libraries to select potential drugs and of
      small interference RNA libraries to identify essential molecules involved in
      critical steps of the immune response.

PMID- 17020933
TI  - Altered frequency-dependent inactivation and steady-state inactivation of
      polyglutamine-expanded alpha1A in SCA6.
AB  - Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease of the
      cerebellum and inferior olives characterized by a late-onset cerebellar ataxia
      and selective loss of Purkinje neurons. SCA6 arises from an expansion of the
      polyglutamine tract located in exon 47 of the alpha(1A) (P/Q-type calcium
      channel) gene from a nonpathogenic size of 4 to 18 glutamines (CAG(4-18)) to
      CAG(19-33) in SCA6. The molecular basis of SCA6 is poorly understood. To date,
      the biophysical properties studied in heterologous systems support both a gain
      and a loss of channel function in SCA6. We studied the behavior of the human
      alpha(1A) isoform, previously found to elicit a gain of function in disease,
      focusing on properties in which the COOH terminus of the channel is critical for
      function: we analyzed the current properties in the presence of beta(4)- and
      beta(2a)-subunits (both known to interact with the alpha(1A) COOH terminus),
      current kinetics of activation and inactivation, calcium-dependent inactivation
      and facilitation, voltage-dependent inactivation, frequency dependence, and
      steady-state activation and inactivation properties. We found that SCA6 channels
      have decreased activity-dependent inactivation and a depolarizing shift (+6 mV)
      in steady-state inactivation properties consistent with a gain of function.

PMID- 17020934
TI  - Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit
      ventricular myocytes.
AB  - The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for
      our understanding of heart disease associated with diabetes and design of its
      treatment. We induced diabetes characterized by hyperglycemia but no other major
      metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic
      rabbits and controls were voltage clamped and internally perfused with the whole
      cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising
      from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding
      current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most
      experiments. There was no effect of diabetes on I(p) recorded when myocytes were
      perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate
      intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a
      significant decrease in I(p) measured when pipette solutions contained 10 mmol/l
      Na(+). The decrease was independent of membrane voltage but dependent on the
      intracellular concentration of K(+). There was no effect of diabetes on the
      sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by
      restoration of euglycemia or by in vivo angiotensin II receptor blockade with
      losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump
      inhibition that can be reversed with pharmacological intervention.

PMID- 17020935
TI  - The mitochondrial energy transduction system and the aging process.
AB  - Aged mammalian tissues show a decreased capacity to produce ATP by oxidative
      phosphorylation due to dysfunctional mitochondria. The mitochondrial content of
      rat brain and liver is not reduced in aging and the impairment of mitochondrial
      function is due to decreased rates of electron transfer by the selectively
      diminished activities of complexes I and IV. Inner membrane H(+) impermeability
      and F(1)-ATP synthase activity are only slightly affected by aging. Dysfunctional
      mitochondria in aged rodents are characterized, besides decreased electron
      transfer and O(2) uptake, by an increased content of oxidation products of
      phospholipids, proteins and DNA, a decreased membrane potential, and increased
      size and fragility. Free radical-mediated oxidations are determining factors of
      mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and
      lifespan. Inner membrane enzyme activities, such as those of complexes I and IV
      and mitochondrial nitric oxide synthase, decrease upon aging and afford aging
      markers. The activities of these three enzymes in mice brain are linearly
      correlated with neurological performance, as determined by the tightrope and the
      T-maze tests. The same enzymatic activities correlated positively with mice
      survival and negatively with the mitochondrial content of lipid and protein
      oxidation products. Conditions that increase survival, as vitamin E dietary
      supplementation, caloric restriction, high spontaneous neurological activity, and
      moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain
      and liver. The pleiotropic signaling of mitochondrial H(2)O(2) and nitric oxide
      diffusion to the cytosol seems modified in aged animals and to contribute to the
      decreased mitochondrial biogenesis in old animals.

PMID- 17020936
TI  - Fat accumulation with altered inflammation and regeneration in skeletal muscle of
      CCR2-/- mice following ischemic injury.
AB  - Chemokines recruit inflammatory cells to sites of injury, but the role of the CC
      chemokine receptor 2 (CCR2) during regenerative processes following ischemia is
      poorly understood. We studied injury, inflammation, perfusion, capillary
      formation, monocyte chemotactic protein-1 (MCP-1) levels, muscle regeneration,
      fat accumulation, and transcription factor activation in hindlimb muscles of CCR2
      /- and wild-type (WT) mice following femoral artery excision (FAE). In both
      groups, muscle injury and restoration of vascular perfusion were similar.
      Nevertheless, edema and neutrophil accumulation were significantly elevated in
      CCR2-/- compared with WT mice at day 1 post-FAE and fewer macrophages were
      present at day 3. MCP-1 levels in post-ischemic calf muscle of CCR2-/- animals
      were significantly elevated over baseline through 14 days post-FAE and were
      higher than WT mice at days 1, 7, and 14. In addition, CCR2-/- mice exhibited
      impaired muscle regeneration, decreased muscle fiber size, and increased
      intermuscular adipocytes with similar capillaries/mm(2) postinjury. Finally, the
      transcription factors, MyoD and signal transducers of and activators of
      transcription-3 (STAT3), were significantly increased above baseline but did not
      differ significantly between groups at any time point post-FAE. These findings
      suggest that increases in MCP-1, and possibly, MyoD and STAT3, may modulate
      molecular signaling in CCR2-/- mice during inflammatory and regenerative events.
      Furthermore, alterations in neutrophil and macrophage recruitment in CCR2-/- mice
      may critically alter the normal progression of downstream regenerative events in
      injured skeletal muscle and may direct myogenic precursor cells in the
      regenerating milieu toward an adipogenic phenotype.

PMID- 17020937
TI  - Rac is a dominant regulator of cadherin-directed actin assembly that is activated
      by adhesive ligation independently of Tiam1.
AB  - Classic cadherins function as adhesion-activated cell signaling receptors. On
      adhesive ligation, cadherins induce signaling cascades leading to actin
      cytoskeletal reorganization that is imperative for cadherin function. In
      particular, cadherin ligation activates actin assembly by the actin-related
      protein (Arp)2/3 complex, a process that critically affects the ability of cells
      to form and extend cadherin-based contacts. However, the signaling pathway(s)
      that activate Arp2/3 downstream of cadherin adhesion remain poorly understood. In
      this report we focused on the Rho family GTPases Rac and Cdc42, which can signal
      to Arp2/3. We found that homophilic engagement of E-cadherin simultaneously
      activates both Rac1 and Cdc42. However, by comparing the impact of dominant
      negative Rac1 and Cdc42 mutants, we show that Rac1 is the dominant regulator of
      cadherin-directed actin assembly and homophilic contact formation. To pursue
      upstream elements of the Rac1 signaling pathway, we focused on the potential
      contribution of Tiam1 to cadherin-activated Rac signaling. We found that Tiam1 or
      the closely-related Tiam2/STEF1 was recruited to cell-cell contacts in an E
      cadherin-dependent fashion. Moreover, a dominant-negative Tiam1 mutant perturbed
      cell spreading on cadherin-coated substrata. However, disruption of Tiam1
      activity with dominant-negative mutants or RNA interference did not affect the
      ability of E-cadherin ligation to activate Rac1. We conclude that Rac1 critically
      influences cadherin-directed actin assembly as part of a signaling pathway
      independent of Tiam1.

PMID- 17020938
TI  - Is active glucose transport present in bovine ciliary body epithelium?
AB  - Hyperglycemia is a major risk factor for diabetic cataract formation. Effective
      regulation of glucose transport by the ciliary body epithelium (CBE) is pivotal
      to normal glycemic control in the anterior eye, which in turn affects the glucose
      level of the crystalline lens. The present study aimed to characterize the
      glucose transport mechanisms across the bovine blood-aqueous barrier (BAB)
      represented by the CBE. With an Ussing-type chamber, the glucose transport
      kinetics were measured and characterized in the presence and absence of various
      glucose transporter inhibitors. The saturation characteristics of the CBE to
      glucose were estimated from an Eadie-Hofstee plot. The mRNA expression of glucose
      transporters in specific regions of the bovine CBE was assessed using RT-PCR. The
      trans-CBE glucose flux was found to be sensitive to the glucose transporter
      inhibitors cytochalasin B, phloretin, and phlorizin. The transport system had a
      kinetic constant of 5.3 mM and a maximum velocity of 349.5 nmol.h(-1).cm(-2).
      Gene expression for GLUT1, GLUT3, GLUT4, GLUT5, and SGLT2 was observed in both
      the pars plana and pars plicata regions of the bovine CBE. This study
      demonstrates that glucose transport across the bovine CBE is primarily passive in
      nature. However, the novel findings of 1) the presence of a phlorizin-sensitive
      glucose flux and 2) gene expression for SGLT2 mean that a potential role for
      active glucose transport cannot be ruled out. The elucidation of the exact
      function of SGLT2 in the bovine CBE may shed important light on the glucose
      transport and physiology of the BAB and inform future studies of glycemic control
      in relation to diabetic cataract formation.

PMID- 17020939
TI  - Gene structure and expression of Kaposi's sarcoma-associated herpesvirus ORF56,
      ORF57, ORF58, and ORF59.
AB  - Though similar to those of herpesvirus saimiri and Epstein-Barr virus (EBV), the
      Kaposi's sarcoma-associated herpesvirus (KSHV) genome features more splice genes
      and encodes many genes with bicistronic or polycistronic transcripts. In the
      present study, the gene structure and expression of KSHV ORF56 (primase), ORF57
      (MTA), ORF58 (EBV BMRF2 homologue), and ORF59 (DNA polymerase processivity
      factor) were analyzed in butyrate-activated KSHV(+) JSC-1 cells. ORF56 was
      expressed at low abundance as a bicistronic ORF56/57 transcript that utilized the
      same intron, with two alternative branch points, as ORF57 for its RNA splicing.
      ORF56 was transcribed from two transcription start sites, nucleotides (nt) 78994
      (minor) and 79075 (major), but selected the same poly(A) signal as ORF57 for RNA
      polyadenylation. The majority of ORF56 and ORF57 transcripts were cleaved at nt
      83628, although other nearby cleavage sites were selectable. On the opposite
      strand of the viral genome, colinear ORF58 and ORF59 were transcribed from
      different transcription start sites, nt 95821 (major) or 95824 (minor) for ORF58
      and nt 96790 (minor) or 96794 (major) for ORF59, but shared overlapping poly(A)
      signals at nt 94492 and 94488. Two cleavage sites, at nt 94477 and nt 94469,
      could be equally selected for ORF59 polyadenylation, but only the cleavage site
      at nt 94469 could be selected for ORF58 polyadenylation without disrupting the
      ORF58 stop codon immediately upstream. ORF58 was expressed in low abundance as a
      monocistronic transcript, with a long 5' untranslated region (UTR) but a short 3'
      UTR, whereas ORF59 was expressed in high abundance as a bicistronic transcript,
      with a short 5' UTR and a long 3' UTR similar to those of polycistronic ORF60 and
      ORF62. Both ORF56 and ORF59 are targets of ORF57 and were up-regulated
      significantly in the presence of ORF57, a posttranscriptional regulator.

PMID- 17020940
TI  - Conformational changes in the VP1-unique region of native human parvovirus B19
      lead to exposure of internal sequences that play a role in virus neutralization
      and infectivity.
AB  - The unique region of the capsid protein VP1 (VP1u) of human parvovirus B19 (B19)
      elicits a dominant immune response and has a phospholipase A(2) (PLA(2))
      activity, which is necessary for the infection. In contrast to the rest of the
      parvoviruses, the VP1u of B19 is thought to occupy an external position in the
      virion, making this region a promising candidate for vaccine development. By
      using a monoclonal antibody against the most-N-terminal portion of VP1u, we
      revealed that this region rich in neutralizing epitopes is not accessible in
      native capsids. However, exposure of capsids to increasing temperatures or low pH
      led to its progressive accessibility without particle disassembly. Although
      unable to bind free virus or to block virus attachment to the cell, the anti-VP1u
      antibody was neutralizing, suggesting that the exposure of the epitope and the
      subsequent virus neutralization occur only after receptor attachment. The
      measurement of the VP1u-associated PLA(2) activity of B19 capsids revealed that
      this region is also internal but becomes exposed in heat- and in low-pH-treated
      particles. In sharp contrast to native virions, the VP1u of baculovirus-derived
      B19 capsids was readily accessible in the absence of any treatment. These results
      indicate that stretches of VP1u of native B19 capsids harboring neutralizing
      epitopes and essential functional motifs are not external to the capsid. However,
      a conformational change renders these regions accessible and triggers the PLA(2)
      potential of the virus. The results also emphasize major differences in the VP1u
      conformation between natural and recombinant particles.

PMID- 17020941
TI  - Human papillomavirus type 5 E6 oncoprotein represses the transforming growth
      factor beta signaling pathway by binding to SMAD3.
AB  - Mechanisms of cellular transformation associated with human papillomavirus type 5
      (HPV5), which is responsible for skin carcinomas in epidermodysplasia
      verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid
      screening and molecular and cellular biology experiments, we found that HPV5
      oncoprotein E6 interacts with SMAD3, a key component in the transforming growth
      factor beta1 (TGF-beta1) signaling pathway. HPV5 E6 inhibits SMAD3
      transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the
      degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV
      HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF
      beta1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.

PMID- 17020942
TI  - Analysis of the cytosolic domains of the hepatitis B virus envelope proteins for
      their function in viral particle assembly and infectivity.
AB  - The hepatitis B virus (HBV) envelope proteins have the ability to assemble three
      types of viral particles, (i) the empty subviral particles (SVPs), (ii) the
      mature HBV virions, and (iii) the hepatitis delta virus (HDV) particles, in cells
      that are coinfected with HBV and HDV. To gain insight into the function of the
      HBV envelope proteins in morphogenesis of HBV or HDV virions, we have
      investigated subdomains of the envelope proteins that have been shown or
      predicted to lie at the cytosolic face of the endoplasmic reticulum membrane
      during synthesis, a position prone to interaction with the inner core structure.
      These domains, referred to here as cytosolic loops I and II (CYL-I and -II,
      respectively), were subjected to mutagenesis. The mutations were introduced in
      the three HBV envelope proteins, designated small, middle, and large (S-HBsAg, M
      HBsAg, and L-HBsAg, respectively). The mutants were expressed in HuH-7 cells to
      evaluate their capacity for self-assembly and formation of HBV or HDV virions
      when HBV nucleocapsid or HDV ribonucleoprotein, respectively, was provided. We
      found that SVP-competent CYL-I mutations between positions 23 and 78 of the S
      domain were permissive to HBV or HDV virion assembly. One mutation (P29A) was
      permissive for synthesis of the S- and M-HBsAg but adversely affected the
      synthesis or stability of L-HBsAg, thereby preventing the assembly of HBV
      virions. Furthermore, using an in vitro infection assay based on the HepaRG cells
      and the HDV model, we have shown that particles coated with envelope proteins
      bearing CYL-I mutations were fully infectious, hence indicating the absence of an
      infectivity determinant in this region. Finally, we demonstrated that the
      tryptophan residues at positions 196, 199, and 201 in CYL-II, which were shown to
      exert a matrix function for assembly of HDV particles (I. Komla-Soukha and C.
      Sureau, J. Virol. 80:4648-4655, 2006), were dispensable for both assembly and
      infectivity of HBV virions.

PMID- 17020943
TI  - A-to-G hypermutation in the genome of lymphocytic choriomeningitis virus.
AB  - The interferon-inducible adenosine deaminase that acts on double-stranded RNA
      (ADAR1-L) has been proposed to be one of the antiviral effector proteins within
      the complex innate immune response. Here, the potential role of ADAR1-L in the
      innate immune response to lymphocytic choriomeningitis virus (LCMV), a widely
      used virus model, was studied. Infection with LCMV clearly upregulated ADAR1-L
      expression and activity. The editing activity of ADAR1-L on an RNA substrate was
      not inhibited by LCMV replication. Accordingly, an adenosine-to-guanosine (A-to
      G) and uracil-to-cytidine (U-to-C) hypermutation pattern was found in the LCMV
      genomic RNA in infected cell lines and in mice. In addition, two hypermutated
      clones with a high level of A-to-G or U-to-C mutations within a short stretch of
      the viral genome were isolated. Analysis of the functionality of viral
      glycoprotein revealed that A-to-G- and U-to-C-mutated LCMV genomes coded for
      nonfunctional glycoprotein at a surprisingly high frequency. Approximately half
      the GP clones with an amino acid mutation lacked functionality. These results
      suggest that ADAR1-L-induced mutations in the viral RNA lead to a loss of viral
      protein function and reduced viral infectivity. This study therefore provides
      strong support for the contribution of ADAR1-L to the innate antiviral immune
      response.

PMID- 17020944
TI  - A new group B adenovirus receptor is expressed at high levels on human stem and
      tumor cells.
AB  - CD46 is used by human group B adenoviruses (Ads) as a high-affinity attachment
      receptor. Here we show evidence that several group B Ads utilize an additional
      receptor for infection of human cells, which is different from CD46. We
      tentatively named this receptor receptor X. Competition studies with unlabeled
      and labeled Ads, recombinant Ad fiber knobs, and soluble CD46 and CD46 antibodies
      revealed three different subgroups of group B Ads, in terms of their receptor
      usage. Group I (Ad16, -21, -35, and -50) nearly exclusively uses CD46. Group II
      (Ad3, -7p, and -14) utilizes receptor X and not CD46. Group III (Ad11p) uses both
      CD46 and the alternative receptor X. Interaction of group II and III Ads with
      receptor X occurs via the fiber knob. Receptor X is an abundantly expressed
      glycoprotein that interacts with group II and III Ads at relatively low affinity
      in a Ca(2+)-dependent manner. This receptor is expressed at high levels on human
      mesenchymal and undifferentiated embryonic stem cells, as well as on human cancer
      cell lines. These findings have practical implications for stem cell and gene
      therapy.

PMID- 17020945
TI  - Proviral progeny of heterodimeric virions reveal a high crossover rate for human
      immunodeficiency virus type 2.
AB  - Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS in
      humans, exhibits a very high rate of recombination. Bearing in mind the
      significant epidemiological and clinical contrast between HIV-2 and HIV-1 as well
      as the critical role that recombination plays in viral evolution, we examined the
      nature of HIV-2 recombination. Towards this end, a strategy was devised to
      measure the rate of crossover of HIV-2 by evaluating recombinant progeny produced
      exclusively by heterodimeric virions. The results showed that HIV-2 exhibits a
      crossover rate similar to that of HIV-1 and murine leukemia virus, indicating
      that the extremely high rate of crossover is a common retroviral feature.

PMID- 17020946
TI  - Indolopyridones inhibit human immunodeficiency virus reverse transcriptase with a
      novel mechanism of action.
AB  - We have discovered a novel class of human immunodeficiency virus (HIV) reverse
      transcriptase (RT) inhibitors that block the polymerization reaction in a mode
      distinct from those of the nucleoside or nucleotide RT inhibitors (NRTIs) and
      nonnucleoside RT inhibitors (NNRTIs). For this class of indolopyridone compounds,
      steady-state kinetics revealed competitive inhibition with respect to the
      nucleotide substrate. Despite substantial structural differences with classical
      chain terminators or natural nucleotides, these data suggest that the nucleotide
      binding site of HIV RT may accommodate this novel class of RT inhibitors. To test
      this hypothesis, we have studied the mechanism of action of the prototype
      compound indolopyridone-1 (INDOPY-1) using a variety of complementary biochemical
      tools. Time course experiments with heteropolymeric templates showed "hot spots"
      for inhibition following the incorporation of pyrimidines (T>C). Moreover,
      binding studies and site-specific footprinting experiments revealed that INDOPY-1
      traps the complex in the posttranslocational state, preventing binding and
      incorporation of the next complementary nucleotide. The novel mode of action
      translates into a unique resistance profile. While INDOPY-1 susceptibility is
      unaffected by mutations associated with NNRTI or multidrug NRTI resistance,
      mutations M184V and Y115F are associated with decreased susceptibility, and
      mutation K65R confers hypersusceptibility to INDOPY-1. This resistance profile
      provides additional evidence for active site binding. In conclusion, this class
      of indolopyridones can occupy the nucleotide binding site of HIV RT by forming a
      stable ternary complex whose stability is mainly dependent on the nature of the
      primer 3' end.

PMID- 17020947
TI  - Adenovirus fiber shaft contains a trimerization element that supports peptide
      fusion for targeted gene delivery.
AB  - Adenoviral (Ad) vectors have been widely used in human gene therapy clinical
      trials. However, their application has frequently been restricted by the
      unfavorable expression of cell surface receptors critical for Ad infection.
      Infections by Ad2 and Ad5 are largely regulated by the elongated fiber protein
      that mediates its attachment to a cell surface receptor, coxsackie and adenovirus
      receptor (CAR). The fiber protein is a homotrimer consisting of an N-terminal
      tail, a long shaft, and a C-terminal knob region that is responsible for high
      affinity receptor binding and Ad tropism. Consequently, the modification of the
      knob region, including peptide insertion and C-terminal fusion of ligands for
      cell surface receptors, has become a major research focus for targeting gene
      delivery. Such manipulation tends to disrupt fiber assembly since the knob region
      contains a stabilization element for fiber trimerization. We report here the
      identification of a novel trimerization element in the Ad fiber shaft. We
      demonstrate that fiber fragments containing the N-terminal tail and shaft repeats
      formed stable trimers that assembled onto Ad virions independently of the knob
      region. This fiber shaft trimerization element (FSTE) exhibited a capacity to
      support peptide fusion. We showed that Ad, modified with a chimeric protein by
      direct fusion of the FSTE with a growth factor ligand or a single-chain antibody,
      delivered a reporter gene selectively. Together, these results indicate that the
      shaft region of Ad fiber protein contains a trimerization element that allows
      ligand fusion, which potentially broadens the basis for Ad vector development.

PMID- 17020948
TI  - Effect of adenovirus-mediated RNA interference on endogenous microRNAs in a mouse
      model of multidrug resistance protein 2 gene silencing.
AB  - RNA interference with viral vectors that express short hairpin RNAs (shRNAs) has
      emerged as a powerful tool for functional genomics and therapeutic purposes.
      However, little is known about shRNA in vivo processing, accumulation, functional
      kinetics, and side effects related to shRNA saturation of the cellular gene
      silencing machinery. Therefore, we constructed first-generation recombinant
      adenoviruses encoding different shRNAs against murine ATP-binding cassette
      multidrug resistance protein 2 (Abcc2), which is involved in liver transport of
      bilirubin to bile, and analyzed Abcc2 silencing kinetics. C57/BL6 mice injected
      with these viruses showed significant impairment of Abcc2 function for up to 3
      weeks, as reflected by increased serum bilirubin levels. The lack of Abcc2
      function correlated with a specific reduction of Abcc2 mRNA and with high levels
      of processed shRNAs targeting Abcc2. Inhibition was lost at longer times
      postinfection, correlating with a decrease in the accumulation of processed
      shRNAs. This finding suggests that a minimal amount of processed shRNAs is
      required for efficient silencing in vivo. This system was also used to evaluate
      the effect of shRNA expression on the saturation of silencing factors. Saturation
      of the cellular silencing processing machinery alters the accumulation and
      functionality of endogenous microRNAs (miRNAs) and pre-miRNAs. However,
      expression of functional exogenous shRNAs did not change the levels of endogenous
      miRNAs or their precursors. In summary, this work shows that adenoviral vectors
      can deliver sufficient shRNAs to mediate inhibition of gene expression without
      saturating the silencing machinery.

PMID- 17020949
TI  - Activation of microglia by borna disease virus infection: in vitro study.
AB  - Neonatal Borna disease virus (BDV) infection of the rat brain is associated with
      microglial activation and damage to the certain neuronal populations. Since
      persistent BDV infection of neurons in vitro is noncytolytic and noncytopathic,
      activated microglia have been suggested to be responsible for neuronal cell death
      in vivo. However, the mechanisms of activation of microglia in neonatally BDV
      infected rat brain have not been investigated. To address these issues,
      activation of primary rat microglial cells was studied following exposure to
      purified BDV or to persistently BDV-infected primary cortical neurons or after
      BDV infection of primary mixed neuron-glial cultures. Neither purified virus nor
      BDV-infected neurons alone activated primary microglia as assessed by the changes
      in cell shape or production of the proinflammatory cytokines. In contrast, in the
      BDV-infected primary mixed cultures, we observed proliferation of microglia cells
      that acquired the round morphology and expressed major histocompatibility complex
      molecules of classes I and II. These manifestations of microglia activation were
      observed in the absence of direct BDV infection of microglia or overt neuronal
      toxicity. In addition, compared to uninfected mixed cultures, activation of
      microglia in BDV-infected mixed cultures was associated with a significantly
      greater lipopolysaccharide-induced release of tumor necrosis factor alpha,
      interleukin 1beta, and interleukin 10. Taken together, the present data are the
      first in vitro evidence that persistent BDV infection of neurons and astrocytes
      rather than direct exposure to the virus or dying neurons is critical for
      activating microglia.

PMID- 17020950
TI  - RNA- and virus-independent inhibition of antiviral signaling by RNA helicase
      LGP2.
AB  - Antiviral innate immune responses can be triggered by accumulation of
      intracellular nucleic acids resulting from virus infections. Double-stranded RNA
      (dsRNA) can be detected by the cytoplasmic RNA helicase proteins RIG-I and MDA5,
      two proteins that share sequence similarities within a caspase recruitment domain
      (CARD) and a DExD/H box RNA helicase domain. These proteins are considered dsRNA
      sensors and are thought to transmit the signal to the mitochondrial adapter, IPS
      1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. IPS-1 coordinates
      the activity of protein kinases that activate transcription factors needed to
      induce beta interferon (IFN-beta) gene transcription. Another helicase protein,
      LGP2, lacks the CARD region and does not activate IFN-beta gene expression. LGP2
      mRNA is induced by interferon, dsRNA treatments, or Sendai virus infection and
      acts as a feedback inhibitor for antiviral signaling. Results indicate that LGP2
      can inhibit antiviral signaling independently of dsRNA or virus infection
      intermediates by engaging in a protein complex with IPS-1. Experiments suggest
      that LGP2 can compete with the kinase IKKi (also known as IKKepsilon) for a
      common interaction site on IPS-1. These results provide the first demonstration
      of protein interaction as an element of negative-feedback regulation of
      intracellular antiviral signaling by LGP2.

PMID- 17020951
TI  - Kaposi's sarcoma-associated herpesvirus ori-Lyt-dependent DNA replication: dual
      role of replication and transcription activator.
AB  - Lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential
      for viral propagation and pathogenicity. In Kaposi's sarcoma lesions, constant
      lytic replication plays a role in sustaining the population of latently infected
      cells that otherwise are quickly lost by segregation of latent viral episomes as
      spindle cells divide. Lytic DNA replication initiates from an origin (ori-Lyt)
      and requires trans-acting elements. Two functional ori-Lyts have been identified
      in the KSHV genome. Some cis-acting and trans-acting elements for ori-Lyt
      dependent DNA replication have been found. Among these, K8 binding sites, a
      cluster of C/EBP binding motifs, and a replication and transcription activator
      (RTA) responsive element (RRE) are crucial cis-acting elements. Binding of K8 and
      RTA proteins to these motifs in ori-Lyt DNA was demonstrated to be absolutely
      essential for DNA replication. In the present study, functional roles of RTA in
      ori-Lyt-dependent DNA replication have been investigated. Two distinct functions
      of RTA were revealed. First, RTA activates an ori-Lyt promoter and initiates
      transcription across GC-rich tandem repeats. This RTA-mediated transcription is
      indispensable for DNA replication. Second, RTA is a component of the replication
      compartment, where RTA interacts with prereplication complexes composed of at
      least six core machinery proteins and K8. The prereplication complexes are
      recruited to ori-Lyt DNA through RTA, which interacts with the RRE, as well as
      K8, which binds to a cluster of C/EBP binding motifs with the aid of C/EBP alpha.
      The revelation of these two functions of RTA, together with its role in
      initiation of a transcriptional cascade that leads to transcription of all viral
      lytic genes, shows that RTA is a critical initiator and regulator of KSHV lytic
      DNA replication and viral propagation.

PMID- 17020952
TI  - Strain fidelity of chronic wasting disease upon murine adaptation.
AB  - Chronic wasting disease (CWD), a prion disease of deer and elk, is highly
      prevalent in some regions of North America. The establishment of mouse-adapted
      CWD prions has proven difficult due to the strong species barrier between mice
      and deer. Here we report the efficient transmission of CWD to transgenic mice
      overexpressing murine PrP. All mice developed disease 500 +/- 62 days after
      intracerebral CWD challenge. The incubation period decreased to 228 +/- 103 days
      on secondary passage and to 162 +/- 6 days on tertiary passage. Mice developed
      very large, radially structured cerebral amyloid plaques similar to those of CWD
      infected deer and elk. PrP(Sc) was detected in spleen, indicating that murine CWD
      was lymphotropic. PrP(Sc) glycoform profiles maintained a predominantly
      diglycosylated PrP pattern, as seen with CWD in deer and elk, across all
      passages. Therefore, all pathological, biochemical, and histological strain
      characteristics of CWD appear to persist upon repetitive serial passage through
      mice. These findings indicate that the salient strain-specific properties of CWD
      are encoded by agent-intrinsic components rather than by host factors.

PMID- 17020953
TI  - The 2006 Bernard B. Brodie Award Lecture. Cyp2e1.
AB  - Bernard B. Brodie's laboratory was the first to examine the mechanisms of drug
      induced toxicity at the molecular level. They found that acetaminophen
      hepatotoxicity was due to the metabolic activation of the drug to a highly
      reactive toxic metabolite that depleted cellular glutathione and covalently bound
      to protein. Subsequent studies revealed that activation of acetaminophen to an
      active metabolite is primarily carried out by CYP2E1, an ethanol-inducible
      cytochrome P450 that was first suggested by characterization of the microsomal
      ethanol oxidation system. CYP2E1 is developmentally regulated, under liver
      specific control, and undergoes substrate-induced protein stabilization. It is
      also regulated by starvation and diabetes through insulin-dependent mRNA
      stabilization. In addition to acetaminophen, CYP2E1 metabolically activates a
      large number of low M(r) toxicants and carcinogens and thus is of great
      toxicological importance. The mechanism of regulation CYP2E1 and its role in
      acetaminophen toxicity will be discussed.

PMID- 17020954
TI  - PEGylated proteins: evaluation of their safety in the absence of definitive
      metabolism studies.
AB  - During the development of any PEGylated protein or peptide, toxicology in
      relevant species will be conducted prior to human exposure. Normally,
      comprehensive metabolism data accompany the toxicity studies for a small
      molecule. We have examined whether such studies would be relevant in the safety
      assessment of PEGylated material. Literature data indicate that the polyethylene
      glycol (PEG) associated with a biological molecule should provide no extra
      concern because the exposure-toxicity relationship of PEG in animals and humans
      has been thoroughly investigated and metabolism/excretion of PEG is well
      understood. Based on the comparisons of PEG exposure from PEGylated biological
      products and the exposure of PEG associated with toxicity in humans, the
      therapeutic index is large (approximately 600-fold or greater). Therefore,
      assuming that toxicological evaluation of a biological molecule of interest is
      complete and satisfactory therapeutic windows are achieved, the data contained in
      this review indicate that the PEG associated with a protein or other biological
      molecule does not represent an additional unquantified risk to humans.

PMID- 17020955
TI  - Identification of human cytochrome p450 isozymes involved in diphenhydramine N
      demethylation.
AB  - Diphenhydramine is widely used as an over-the-counter antihistamine. However, the
      specific human cytochrome P450 (P450) isozymes that mediate the metabolism of
      diphenhydramine in the range of clinically relevant concentrations (0.14-0.77
      microM) remain unclear. Therefore, P450 isozymes involved in N-demethylation, a
      main metabolic pathway of diphenhydramine, were identified by a liquid
      chromatography-mass spectrometry method developed in our laboratory. Among 14
      recombinant P450 isozymes, CYP2D6 showed the highest activity of diphenhydramine
      N-demethylation (0.69 pmol/min/pmol P450) at 0.5 microM. CYP2D6 catalyzed
      diphenhydramine N-demethylation as a high-affinity P450 isozyme, the K(m) value
      of which was 1.12 +/- 0.21 microM. In addition, CYP1A2, CYP2C9, and CYP2C19 were
      identified as low-affinity components. In human liver microsomes, involvement of
      CYP2D6, CYP1A2, CYP2C9, and CYP2C19 in diphenhydramine N-demethylation was
      confirmed by using P450 isozyme-specific inhibitors. In addition, contributions
      of these P450 isozymes estimated by the relative activity factor were in good
      agreement with the results of inhibition studies. Although an inhibitory effect
      of diphenhydramine on the metabolic activity of CYP2D6 has been reported
      previously, the results of the present study suggest that it is not only a potent
      inhibitor but also a high-affinity substrate of CYP2D6. Therefore, it is worth
      mentioning that the sedative effect of diphenhydramine might be caused by
      coadministration of CYP2D6 substrate(s)/inhibitor(s). In addition, large
      differences in the metabolic activities of CYP2D6 and those of CYP1A2, CYP2C9,
      and CYP2C19 could cause the individual differences in anti-allergic efficacy and
      the sedative effect of diphenhydramine.

PMID- 17020956
TI  - Organic anion transporting polypeptide 2B1 and breast cancer resistance protein
      interact in the transepithelial transport of steroid sulfates in human placenta.
AB  - The human placenta has both protective and nurturing functions for the fetal
      organism. Uptake and elimination of xenobiotics and endogenous substances are
      facilitated by various transport proteins from the solute carrier (SLC) and ABC
      families, respectively. A functional interaction of uptake and elimination, which
      is a prerequisite for vectorial transport across cellular barriers, has not been
      described for placenta. In this study, we examined expression of organic anion
      transporter (OAT) 4 (SLC22A11), organic anion transporting polypeptide (OATP) 2B1
      (SLCO2B1, OATP-B), and breast cancer resistance protein (BCRP) (ABCG2) in human
      placenta (n = 71) because all three proteins are involved in transmembranal
      transfer of estrone 3 sulfate (E3S; metabolic product) and dehydroepiandrosterone
      sulfate (DHEAS; precursor molecule). On the mRNA level, we found a significant
      correlation of OATP2B1 and BCRP (R(2) = 0.534; p < 0.01) but not between OAT4 and
      BCRP (R(2) = -0.104; p > 0.05). Localization studies confirmed basal expression
      of OATP2B1 and apical expression of BCRP. To study functional interactions
      between OATP2B1 and BCRP, we developed a Madin-Darby canine kidney cell model
      expressing both transport proteins simultaneously (OATP2B1 and BCRP in the basal
      and apical membrane, respectively). Using this cell model in a transwell system
      resulted in a significantly increased basal to apical transport of both E3S and
      DHEAS, when both transporters were expressed with no change of transfer in the
      apical to basal direction. Taken together, these data show the potential for a
      functional interaction of OATP2B1 and BCRP in transepithelial transport of
      steroid sulfates in human placenta.

PMID- 17020957
TI  - A novel model for the prediction of drug-drug interactions in humans based on in
      vitro cytochrome p450 phenotypic data.
AB  - Ketoconazole has generally been used as a standard inhibitor for studying
      clinical pharmacokinetic drug-drug interactions (DDIs) of drugs that are
      primarily metabolized by CYP3A4/5. However, ketoconazole at therapeutic, high
      concentrations also inhibits cytochromes P450 (P450) other than CYP3A4/5, which
      has made the predictions of DDIs less accurate. Determining the in vivo inhibitor
      concentration at the enzymatic site is critical for predicting the clinical DDI,
      but it remains a technical challenge. Various approaches have been used in the
      literature to estimate the human hepatic free concentrations of this inhibitor,
      and application of those to predict DDIs has shown some success. In the present
      study, a novel approach using cryopreserved human hepatocytes suspended in human
      plasma was applied to mimic the in vivo concentration of ketoconazole at the
      enzymatic site. The involvement of various P450s in the metabolism of compounds
      of interest was quantitatively determined (reactive phenotyping). Likewise, the
      effect of ketoconazole on various P450s was quantitated. Using this information,
      P450-mediated change in the area under the curve has been predicted without the
      need of estimating the inhibitor concentrations at the enzyme active site or the
      K(i). This approach successfully estimated the magnitude of the clinical DDI of
      an investigational compound, MLX, which is cleared by multiple P450-mediated
      metabolism. It also successfully predicted the pharmacokinetic DDIs for several
      marketed drugs (theophylline, tolbutamide, omeprazole, desipramine, midazolam,
      alprazolam, cyclosporine, and loratadine) with a correlation coefficient (r(2))
      of 0.992. Thus, this approach provides a simple method to more precisely predict
      the DDIs for P450 substrates when coadministered with ketoconazole or any other
      competitive P450 inhibitors in humans.

PMID- 17020958
TI  - Gender dictates the nuclear receptor-mediated regulation of CYP3A44.
AB  - The CYP3As are broad-spectrum drug-metabolizing enzymes that are collectively
      responsible for more than 50% of xenobiotic metabolism. Unlike other CYP3As,
      murine CYP3A44 is expressed predominantly in the female liver, with much lower
      levels in male livers and no detectable expression in brain or kidney in either
      gender. In this study, we examined the role of nuclear hormone receptors in the
      regulation of Cyp3a44 gene expression. Interestingly, we observed differential
      effects of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) 
      mediated activation of Cyp3a44 gene expression, which was gender-specific. For
      example, activation of PXR by pregnenolone-16alpha-carbonitrile (PCN) and
      dexamethasone (DEX) induced CYP3A44 mRNA levels in a PXR-dependent fashion in
      male mice, whereas no induction was detected in female mice. In contrast, PCN and
      DEX down-regulated CYP3A44 expression in female PXR null animals. Similar to PXR,
      CAR activation also showed a male-specific induction with no effect on CYP3A44
      levels in females. When PXR knockout mice were challenged with the CAR activator
      phenobarbital, a significant up-regulation of male CYP3A44 levels was observed,
      whereas levels in females remained unchanged. We conclude that gender has a
      critical impact on PXR- and CAR-mediated effects of CYP3A44 expression.

PMID- 17020960
TI  - Cancer stem cells and metastasis: lethal seeds.

PMID- 17020961
TI  - Monitoring targeted therapy: is fluorodeoxylucose uptake a marker of early
      response?

PMID- 17020962
TI  - Insulin-like growth factor-I axis as a pathway for cancer chemoprevention.

PMID- 17020963
TI  - Most early disseminated cancer cells detected in bone marrow of breast cancer
      patients have a putative breast cancer stem cell phenotype.
AB  - PURPOSE: The presence of disseminated tumor cells (DTC) in the bone marrow of
      breast cancer patients is an acknowledged independent prognostic factor. The
      biological metastatic potential of these cells has not yet been shown. The
      presence of putative breast cancer stem cells is shown both in primary tumors and
      distant metastases. These cells with a CD44(+)CD24(-/low) phenotype represent a
      minor population in primary breast cancer and are associated with self-renewal
      and tumorigenic potential. Recognizing the potential effect of prevalence of
      putative stem cells among DTC, we evaluated the bone marrow DTC. EXPERIMENTAL
      DESIGN: We employed the double/triple-staining immunohistochemistry protocol and
      modified the established bone marrow cytokeratin (CK) staining protocol by adding
      steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow
      specimens, previously categorized as CK(+) from early breast cancer patients.
      CK(+) cells were examined for CD44 and CD24 expression by light microscopy,
      fluorescence microscopy, and spectral imaging. RESULTS: We detected the putative
      stem cell-like phenotype in all CK(+) specimens. The mean prevalence of putative
      stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%)
      among the overall DTC per patient, compared with primary tumors where this
      phenotype is reported in <10% of cells. CONCLUSIONS: This is the first evidence
      of the existence of the putative stem-like phenotype within the DTC in bone
      marrow in early breast cancer patients. All patients had a putative stem cell
      phenotype among the DTC and most individual DTC showed such phenotype. Future
      molecular characterization of these cells is warranted.

PMID- 17020964
TI  - Magnitude of stromal hemangiogenesis correlates with histologic subtype of non
      Hodgkin's lymphoma.
AB  - PURPOSE: Tumor stromal microenvironment promotes neoplastic growth and
      angiogenesis. We have previously shown that recruitment of marrow-derived
      vascular endothelial growth factor receptor-1(+) (VEGFR-1(+)) proangiogenic
      hematopoietic progenitors contributes instructively and structurally to
      neoangiogenesis in mouse models. Here, we investigated whether stromal
      incorporation of CD68(+) hemangiogenic cells and alpha-smooth muscle actin(+)
      (alpha-SMA(+)) stromal cells correlates with neoangiogenesis and progression in
      human non-Hodgkin's lymphoma subtypes. EXPERIMENTAL DESIGN: Spatial localizations
      of vascular and stromal cells expressing CD34, VEGFR-1, alpha-SMA, and CD68 were
      examined by immunohistochemistry in 42 cases of non-Hodgkin's lymphoma, including
      diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, and chronic
      lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and compared with
      benign follicular hyperplasia. RESULTS: Compared with indolent lymphomas, there
      was a profound increase in recruitment of CD68(+) cells and VEGFR-1(+) neovessels
      in aggressive subtypes (including those transformed from indolent subtypes),
      where CD68(+) cells were localized to the perivascular region of neovessels as
      well as the stromal compartment. The perivascular CD68(+) cells expressed VEGFR-1
      and VEGF-A. In contrast, there was a diffuse increase in alpha-SMA incorporation
      throughout the stromal compartment of indolent subtype of CLL/SLL compared with
      the scant perivascular pattern in aggressive subtypes. Overall, there was no
      correlation between CD34(+) microvessel density and lymphoma histologic subtype.
      CONCLUSIONS: Heightened stromal hemangiogenesis as marked by infiltration of
      proangiogenic VEGFR-1(+)CD68(+)VEGF-A(+) cells and their paracrine cross-talk
      with neovasculature appears to be a distinct feature of aggressive lymphoma,
      providing novel targets for antiangiogenic therapy, whereas alpha-SMA(+) stromal
      vascular network may be differentially targeted in CLL/SLL.

PMID- 17020965
TI  - Gene expression profiling in cervical cancer: an exploration of intratumor
      heterogeneity.
AB  - PURPOSE: To explore intratumor heterogeneity in gene expression profiles from
      patients with cervical cancer. EXPERIMENTAL DESIGN: A total of 33 biopsies were
      obtained from 11 patients, sampling between two and five different areas for each
      tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0
      oligonucleotide chip. The variance of expression within a patient (W), between
      patients (B) and the total variance (T = W + B) were calculated for each
      ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity.
      Gene Ontology functional analysis was done to assess the function of genes that
      had high W/T (top 10%) and low W/T (bottom 10%) values. RESULTS: In total, 448
      ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor
      heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating
      high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher
      intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor
      heterogeneity were characterized by a statistically significant enrichment of
      immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity
      were characterized by a significant tendency towards nuclear localization and
      nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six
      biopsies would be required to minimize the intratumoral heterogeneity to <0.15;
      if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3,
      only two to three biopsies would be needed. CONCLUSION: Although the intratumor
      heterogeneity was low for the majority of the tested ProbeSets, for many genes,
      multiple biopsies are required to obtain a reliable estimate of gene expression.

PMID- 17020966
TI  - Expression of terminally glycosylated calcitonin receptor-like receptor in
      uterine leiomyoma: endothelial phenotype and association with microvascular
      density.
AB  - PURPOSE: The role for the hypoxia-inducible angiogenic factor adrenomedullin (AM)
      in tumor growth and progression has been suggested. Calcitonin receptor-like
      receptor (CL) is a G protein-coupled receptor (GPCR) that mediates effects of AM,
      but little information is available on its expression and functional state in
      human tumors. The present study attempted to determine CL potential for
      antiangiogenic therapy of uterine leiomyoma. EXPERIMENTAL DESIGN AND RESULTS:
      GPCR CL is transported to the cell surface and recognized by AM only when
      terminally/mature glycosylated. The presence and localization of this form of the
      receptor in tumor and surrounding myometrial tissues obtained from leiomyoma
      bearing uteri were examined using deglycosylation, immunoblotting, and
      immunofluorescence analysis. The mature CL glycoprotein was expressed in both
      tissues and localized exclusively in normal and tumor endothelium within
      leiomyoma-bearing uteri. The functionality of the receptor expressed in
      myometrial microvascular endothelial cells (MMVEC) was examined in vitro using
      receptor internalization and angiogenic assays. The mature CL glycoprotein
      expressed by primary MMVECs was functional because AM interacted with this GPCR
      and induced its internalization as well as angiogenic effects (proliferation and
      migration) in MMVECs in vitro. Finally, the levels of tissue-expressed mature CL
      glycoprotein as a functional form of this GPCR were analyzed by immunoblotting.
      The expression of this functional form of the receptor in vivo was significantly
      decreased (P = 0.01) in leiomyoma tissue, and this was concurrent with the
      decrease in microvascular density (measured by Chalkley counting) in tumor
      compared with surrounding myometrium (P = 0.031). CONCLUSIONS: Our findings
      suggest that GPCR CL mediates angiogenic effects of AM in myometrium and that
      further evaluation of the properties of the CL expressed in both normal and tumor
      endothelium in vivo may be essential before targeting this endothelial GPCR for
      antiangiogenic therapies.

PMID- 17020967
TI  - Monitoring tumor glucose utilization by positron emission tomography for the
      prediction of treatment response to epidermal growth factor receptor kinase
      inhibitors.
AB  - PURPOSE: The mechanisms underlying the sensitivity of non-small cell lung cancer
      to epidermal growth factor receptor (EGFR) kinase inhibitors are complex, and
      there are no established markers to accurately predict treatment outcome in
      individual patients. EXPERIMENTAL DESIGN: We investigated whether tumors
      responding to EGFR inhibitors can be identified by measuring treatment-induced
      changes in glucose utilization by positron emission tomography with the glucose
      analogue fluorodeoxyglucose (FDG-PET). We studied a panel of cell lines with a
      spectrum of sensitivity to EGFR kinase inhibitors. After incubation with the EGFR
      kinase inhibitor gefitinib for various time points, FDG uptake, glucose transport
      rates, and hexokinase activity were determined. FDG uptake in vivo was assessed
      by microPET imaging of tumor xenografts in mice. RESULTS: In gefitinib-sensitive
      cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after
      treatment. Immunoblots showed the translocation of glucose transporters (GLUT3)
      from the plasma membrane to the cytosol; glucose transport rates were reduced 2.6
      fold at this time. There was also a modest reduction of hexokinase activity.
      These metabolic alterations preceded changes in cell cycle distribution,
      thymidine uptake, and apoptosis. MicroPET studies showed an up to 55% decrease of
      tumor FDG uptake in sensitive xenografts within 48 hours. In contrast, gefitinib
      resistant cells exhibited no measurable changes in FDG uptake, either in cell
      culture or in vivo. CONCLUSION: Glucose metabolic activity closely reflects
      response to gefitinib therapy. FDG-PET may be a valuable clinical predictor,
      early in the course of treatment, for therapeutic responses to EGFR kinase
      inhibitors.

PMID- 17020968
TI  - Interphase fluorescence in situ hybridization analysis of chromosome 12p
      abnormalities is useful for distinguishing epidermoid cysts of the testis from
      pure mature teratoma.
AB  - PURPOSE: The distinction of epidermoid cyst of the testis from teratoma is of
      critical importance because the former is benign and the latter is a malignant
      tumor that may have associated metastasis of either teratomatous or non
      teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the
      vast majority of testicular germ cell tumors of adults and are present in all
      histologic subtypes. In this study, we investigated the clinical utility of
      interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p
      abnormalities for distinguishing epidermoid cysts of the testis from pure mature
      teratoma. EXPERIMENTAL DESIGN: Sixteen testicular epidermoid cysts and 17
      testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p
      overrepresentation using interphase FISH analysis. RESULTS: Neither i(12p) nor
      12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p)
      was detected in 76% of teratomas and 12p overrepresentation was identified in 29%
      of teratomas. Overall, 88% of testicular teratomas had chromosome 12p
      abnormalities. CONCLUSIONS: FISH identification of i(12p) and/or 12p
      overrepresentation in routinely processed surgical specimens is a useful
      ancillary diagnostic tool in distinguishing testicular epidermoid cysts from
      teratoma.

PMID- 17020969
TI  - Increased expression of Wiskott-Aldrich syndrome protein family verprolin
      homologous protein 2 correlated with poor prognosis of hepatocellular carcinoma.
AB  - PURPOSE: Because of its role in cell migration, the Wiskott-Aldrich syndrome
      protein family verprolin-homologous protein (WAVE) 2 has been implicated in
      cancer metastasis. Evidence to support such a role of WAVE2 in human cancer,
      however, is lacking. We thus examined the expression of WAVE2 in hepatocellular
      carcinoma (HCC) tissues to test whether the levels of WAVE2 expression correlated
      to the progression of HCC. EXPERIMENTAL DESIGN: Samples of 112 HCC patients were
      determined immunohistochemically for WAVE2 expression and the correlation of
      WAVE2 levels with prognosis was analyzed. Among the 112 cases, 31 paired HCC and
      paracarcinomatous liver tissue specimens were analyzed for WAVE2 levels by
      reverse transcription-PCR and Western blotting, respectively. RESULTS: Among 112
      cases of HCCs, the immunohistochemistry data indicated significant increase of
      WAVE2 expression levels in 71 cases. Importantly, the increased WAVE2 expression
      correlated with the multiple tumor nodules (P = 0.008), the absence of capsular
      formation (P = 0.035), Edmondson-Steiner grade (P = 0.009), vein invasion (P =
      0.023), and a shortened median survival time (326 versus 512 days; P = 0.003).
      Multivariable Cox regression analysis revealed the WAVE2 expression level was an
      independent factor for prognosis. The immunohistochemistry data were further
      confirmed by results of reverse transcription-PCR and Western analysis of 31 HCC
      cases, in which the WAVE2 mRNA and protein in HCC tissues were significantly
      elevated when compared with paracarcinomatous liver tissue (P < 0.001).
      CONCLUSIONS: WAVE2 expression is elevated in HCC tissues, which correlates with a
      poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC.

PMID- 17020970
TI  - Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma
      patients.
AB  - PURPOSE: Contribution of peripheral blood stem cell (PBSC) contaminating tumor
      cells to subsequent relapse and overall survival of neuroblastoma patients
      remains controversial. EXPERIMENTAL DESIGN: Neuroblastoma cell contamination of
      27 PBSC harvests from stage IV neuroblastoma patients was assessed by
      quantitative RT-PCR for both tyrosine hydroxylase (TH) and GD2 synthase (GD2-s).
      The effect of PBSC contamination on survival was then analyzed. RESULTS: Seven
      PBSC tested negative for both markers; 19 were positive for GD2-s, 6 for TH, with
      5 positive for both. Survival of the 20 patients with positive PBSC did not
      differ from that of the patients with negative PBSC (log-rank test, P = 0.134 and
      0.218 for event-free survival and overall survival, respectively). By considering
      the TH and GD2-s results independently, a borderline (P = 0.053) negative effect
      on event-free survival was observed in patients reinfused with GD2-s-positive
      PBSC. When the status at transplant was taken into account, only the event-free
      survival of the patients rescued when in complete remission with GD2-s-negative
      PBSC was better, although not significantly, than that of patients infused with
      GD2-s-positive PBSC. CONCLUSIONS: Our results obtained in a small cohort of
      homogeneously treated stage IV patients suggest that patient survival is not
      affected by PBSC contamination with the exception of a borderline negative effect
      on event-free survival in patients rescued when in complete remission.

PMID- 17020971
TI  - The GNAS1 T393C polymorphism is associated with disease progression and survival
      in chronic lymphocytic leukemia.
AB  - PURPOSE: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the
      accumulation of monoclonal mature B cells. The G protein Galphas subunit has been
      linked to proapoptotic processes in cancer cell lines. The TT genotype of the
      GNAS1 T393C polymorphism is associated with increased Galphas transcript levels
      and a more favorable clinical course in different solid cancers. EXPERIMENTAL
      DESIGN: We retrospectively genotyped 144 patients with B-CLL to examine a
      potential association between T393C genotypes with progression-free survival
      (time from diagnosis to initiation of chemotherapy) and overall survival.
      RESULTS: The C-allele frequency in the patient group was 0.57 and not
      significantly different from that of healthy blood donors. Median progression
      free survival was significantly different between genotypes (TT 130 months; TC
      100 months; CC 31 months; P = 0.0066). Multivariable analysis showed that besides
      of ZAP-70 (P = 0.005) and Binet stage (P < 0.001), the T393C polymorphism was an
      independent prognostic factor for progression-free survival [hazard ratio (HR) CC
      versus TT 2.7; P = 0.010]. In Binet A stages, ZAP-70-positive patients with CC
      genotypes had a HR of 4.4 to receive first therapy compared with ZAP-70-negative
      patients with T-alleles (P = 0.0001). Regarding overall survival, CC genotypes
      (median overall survival, 197 months) were at highest risk for death compared
      with T-alleles (median overall survival, 310 months) in both univariate (HR, 4.8;
      P < 0.0001) and multivariable analysis (HR, 5.6; P = 0.002). CONCLUSIONS: Here,
      we show that the GNAS1 T393C status is a novel independent prognostic marker in
      patients with B-CLL. These results could help to define patients who could
      benefit from an early individualized therapy.

PMID- 17020972
TI  - Does MYCN amplification manifested as homogeneously staining regions at diagnosis
      predict a worse outcome in children with neuroblastoma? A Children's Oncology
      Group study.
AB  - PURPOSE: MYCN amplification in neuroblastoma tumor cells is manifested primarily
      as double minutes (dmins), whereas in cell lines it often appears in the form of
      homogeneously staining regions (HSR), suggesting that HSRs are associated with a
      more aggressive tumor phenotype and worse clinical outcome. The aim of this study
      was to determine whether children with neuroblastoma in which MYCN oncogene
      amplification is manifested as HSRs at diagnosis have a worse prognosis than
      those whose tumors exhibit dmins. EXPERIMENTAL DESIGN: A retrospective analysis
      of primary neuroblastomas analyzed for MYCN amplification by the Children's
      Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification
      were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with
      currently used risk group stratification variables and patient outcome were
      assessed. RESULTS: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN
      amplification. Among the 677 tumors for which the pattern of amplification was
      known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs.
      Although MYCN amplification is associated with older age, higher stage, and
      unfavorable histology, whether the amplification occurred as dmins or HSRs did
      not significantly affect these risk factors. There were no differences in the
      event-free survival (EFS) or overall survival in patients with MYCN amplification
      manifested as either dmins or HSRs (5-year EFS, 35 +/- 3% versus 38 +/- 15%; P =
      0.59). Although the eight patients with dmins + HSRs fared worse than either of
      the individual subgroups (EFS, 18 +/- 16% versus 35 +/- 3% for dmins and 38 +/-
      15% for HSRs), these differences were not significant. CONCLUSIONS: MYCN
      amplification in any form (HSRs or dmins) is associated with a poor outcome.

PMID- 17020973
TI  - YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients
      with high-grade gliomas.
AB  - PURPOSE: Biomarkers can facilitate diagnosis, monitor treatment response, and
      assess prognosis in some patients with cancer. YKL-40 and matrix
      metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by
      malignant gliomas. We obtained prospective longitudinal serum samples from
      patients with gliomas to determine whether YKL-40 or MMP-9 could be used as serum
      markers. EXPERIMENTAL DESIGN: Serum samples were obtained concurrently with
      magnetic resonance imaging scans. YKL-40 and MMP-9 were determined by ELISA and
      the values correlated with the patient's radiographic status and survival.
      RESULTS: High-grade glioma patients who underwent a surgical resection of their
      tumor had transient increase of both YKL-40 and MMP-9 serum levels in the
      postoperative period. Glioblastoma multiforme (GBM) patients with no radiographic
      evidence of disease (n = 10 patients, 50 samples) had a significantly lower level
      of YKL-40 and MMP-9 than patients with active tumor (n = 66 patients, 209
      samples; P = 0.0003 and 0.0002, respectively). Anaplastic glioma patients with no
      radiographic evidence of disease (n = 32 patients, 107 samples) also had a
      significantly lower level of YKL-40 compared with those patients with active
      tumor (n = 48 patients, 199 samples; P = 0.04). There was a significant inverse
      association between YKL-40 and survival in GBM, hazard ratio (hazard ratio, 1.4;
      P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P = 0.05).
      CONCLUSIONS: YKL-40 and MMP-9 can be monitored in patients' serum and help
      confirm the absence of active disease in GBM and YKL-40 in anaplastic glioma
      patients. YKL-40 can be used as predictor of survival in patients with high-grade
      glioma. Longitudinal studies with a larger patient population are needed to
      confirm these findings.

PMID- 17020974
TI  - Gene expression profiles of primary breast carcinomas from patients at high risk
      for local recurrence after breast-conserving therapy.
AB  - PURPOSE: Several risk factors for local recurrence of breast cancer after breast
      conserving therapy (BCT) have been identified. The identification of additional
      risk factors would be very useful in guiding optimal therapy and also in
      improving understanding of the mechanisms underlying local recurrence. We used
      cDNA microarray analysis to identify gene expression profiles associated with
      local recurrence. EXPERIMENTAL DESIGN: Using 18K cDNA microarrays, gene
      expression profiles were obtained from 50 patients who underwent BCT. Of these 50
      patients, 19 developed a local recurrence; the remaining 31 patients were
      selected as controls as they were free of local recurrence at least 11 years
      after treatment. For 9 of 19 patients, the local recurrence was also available
      for gene expression profiling. Unsupervised and supervised methods of
      classification were used to separate patients in groups corresponding to disease
      outcome and to study the overall gene expression pattern of primary tumors and
      their recurrences. RESULTS: Hierarchical clustering of patients did not show any
      grouping reflecting local recurrence status. Supervised analysis revealed no
      significant set of genes that was able to distinguish recurring tumors from
      nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences
      showed a remarkable similarity in gene expression profile between primary tumors
      and their recurrences. CONCLUSIONS: No significant differences in gene expression
      between primary breast cancer tumors in patients with or without local recurrence
      after BCT were identified. Furthermore, analyses of primary tumors and local
      recurrences show a preservation of the overall gene expression pattern in the
      local recurrence, even after radiotherapy.

PMID- 17020975
TI  - RNASEL gene polymorphisms and the risk of prostate cancer: a meta-analysis.
AB  - PURPOSE: Studies revealing conflicting results on the role of RNASEL
      polymorphisms Glu265X, Arg462Gln, and Asp541Glu on prostate cancer risk led us to
      perform a meta-analysis to investigate the association of these polymorphisms and
      prostate cancer risk. EXPERIMENTAL DESIGN: Relevant studies were selected by
      searching PubMed from January 1996 to August 2005 using keywords "RNASEL gene AND
      prostate cancer." For each study, odds ratio (OR) with 95% confidence interval
      (95% CI) was calculated to estimate the gene effect. Pooled estimates of the OR
      were computed using the random effects model. RESULTS: Ten studies were included
      in the meta-analysis. The overall results suggested no major influence of these
      variants on prostate cancer risk. However, analysis of the Asp541Glu polymorphism
      by ethnic populations showed that Asp/Glu (familial cases versus control: OR,
      1.38; 95% CI, 1.04-1.82; sporadic cases versus control: OR, 1.26; 95% CI, 1.07
      1.48; prostate cancer versus control: OR, 1.29; 95% CI, 1.12-1.48) and Asp/Glu +
      Glu/Glu (familial cases versus control: OR, 1.37; 95% CI, 1.10-1.70; sporadic
      cases versus control: OR, 1.24; 95% CI, 1.07-1.44; prostate cancer versus
      control: OR, 1.27; 95% CI, 1.13-1.44) increased prostate cancer risk in
      Caucasians, thus suggesting a dominant model for the Glu variant. CONCLUSIONS:
      Compared with the genotype Asp/Asp, the Glu variant at the Asp541Glu polymorphism
      increases prostate cancer risk by <2-fold in Caucasians, regardless of family
      history of the disease. This suggests that genuine genetic effects of this
      polymorphism may account for only a part of prostate cancer in the Caucasian
      population.

PMID- 17020976
TI  - Expression of telomere-associated genes as prognostic markers for overall
      survival in patients with non-small cell lung cancer.
AB  - PURPOSE: Human telomeres, which are composed of long, repetitive sequences of
      TTAGGG and a variety of proteins, function as a protective structure capping the
      ends of chromosomes. Telomere dysfunction plays important roles in cancer
      initiation and progression. TRF1, TRF2, POT1, and RAP1 are four major telomere
      proteins that regulate telomere stability and telomere length. We hypothesized
      that the expression of these genes would have significant predictive value for
      cancer development and prognosis. EXPERIMENTAL DESIGN: We compared the mRNA
      expression level of TRF1, TRF2, POT1, and RAP1 between tumor and adjacent normal
      tissues from 148 patients with non-small cell lung cancer using real-time
      quantitative PCR. We then estimated the prognostic value of the mRNA expression
      of these genes in tumors. RESULTS: The expression level of TRF1 was significantly
      lower in tumor tissues than in adjacent normal tissues (P < 0.0001); no
      significant difference was found for TRF2, POT1, and RAP1. The expression of RAP1
      gene in tumors was highly predictive of overall survival. In the Cox proportional
      hazards model, patients with higher RAP1 expression were associated with a
      significantly better survival [hazard ratio (HR), 0.47; 95% confidence interval
      (95% CI), 0.24-0.91]. This improved survival was more prominent in men (HR, 0.45;
      95% CI, 0.22-0.996) and in ever smokers (HR, 0.50; 95% CI, 0.24-1.02). Kaplan
      Meier survival curves showed that patients with higher RAP1 expression had
      significantly longer median survival than patients with lower expression (median
      = 51.21 versus 15.34 months, P < 0.0009). The expressions of TRF2 in tumor
      tissues were significantly correlated with tumor grades (P = 0.0114).
      CONCLUSIONS: RAP1 expression may be a useful biomarker of tumor progression and
      survival.

PMID- 17020977
TI  - Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in
      nasopharyngeal cancer.
AB  - PURPOSE: Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma which is
      intimately associated with EBV. The latent presence of EBV affects the function
      of p53, Bcl-2, and survivin. We thus investigated the relationship between EBV
      status, p53, Bcl-2, and survivin in biopsy specimens from patients with primary
      NPC. EXPERIMENTAL DESIGN: Archival formalin-fixed, paraffin-embedded NPC biopsies
      were evaluated in 80 patients treated with curative radiation from a single
      institution. The presence of EBV was determined using EBER in situ hybridization,
      whereas p53, Bcl-2, and survivin were assessed using immunohistochemistry.
      RESULTS: The majority of NPC specimens in this patient cohort were EBER-positive
      (64 of 78, or 82%), which in turn, was significantly associated with ethnicity (P
      = 0.0007), and WHO subtype 2A/2B (P = 0.04). EBER-positive tumors were also
      associated with p53 (P = 0.002), Bcl-2 (P = 0.04), and nuclear survivin (P =
      0.03) expression. Patients with EBER-positive NPC fared better, with a 10-year
      overall survival of 68% versus 48% for EBER-negative patients (P = 0.03). For
      nuclear survivin, patients with either low or high nuclear survivin fared worse
      than patients with intermediate survivin expression (P = 0.05), suggesting that
      there is an optimal proportion of survivin-expressing cells for best function and
      clinical outcome. CONCLUSIONS: With an extended median follow-up time of 11.4
      years, EBV status remains a strong predictor for overall survival in NPC. EBV
      positive NPC has strong molecular associations with p53, Bcl-2, and survivin
      expression. Furthermore, we provide clinical data revealing the potentially dual
      nature of survivin in predicting clinical outcome.

PMID- 17020978
TI  - Extracellular pH and P-31 magnetic resonance spectroscopic variables are related
      to outcome in canine soft tissue sarcomas treated with thermoradiotherapy.
AB  - PURPOSE: The objective was to test whether tumor pH and (31)P magnetic resonance
      spectroscopic end points were related to treatment outcome in pet canine patients
      with spontaneous soft tissue sarcomas treated with thermoradiotherapy.
      EXPERIMENTAL DESIGN: Forty-two dogs with evaluable (31)P magnetic resonance
      spectroscopic end points and pH data were included in this study. Tumor variables
      (grade and volume), extracellular pH (pHe), T(2) relaxation times, intracellular
      pH, and selected phosphometabolite ratios were examined for correlation with
      clinical outcome. RESULTS: From 39 dogs, pHe was a predictor of metastasis-free
      survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS)
      with (HR, 0.36; P = 0.013). Tumor volume (>19 cm(3)) was related to MFS (HR,
      2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P
      = 0.03). There was no association between T(2) or intracellular pH and clinical
      outcome. Tumor grade (high versus low/intermediate) and phosphodiester/betaATP
      ratio were identified as significant predictors for MFS, with (HR, 2.66; P =
      0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR,
      2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The
      phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24;
      P = 0.017). CONCLUSIONS: pHe was predictive of metastasis and OS in canine
      spontaneous sarcomas. To our knowledge, this is the first time that pHe has been
      shown to be predictive of clinical outcome. The results suggest that additional
      studies should be considered evaluating the prognostic significance of this
      variable. Phospholipid resonances, related to membrane metabolism, were related
      to clinical outcome, confirming recent results reported in human patients with
      soft tissue sarcomas treated with thermoradiotherapy.

PMID- 17020979
TI  - Nuclear localization of nuclear factor-kappaB p65 in primary prostate tumors is
      highly predictive of pelvic lymph node metastases.
AB  - PURPOSE: Lymph node invasion (LNI) is associated with increased risk of prostate
      cancer progression. Unfortunately, pelvic lymph node dissections are fraught with
      a high rate of false-negative findings, emphasizing the need for highly accurate
      markers of LNI. Because nuclear factor-kappaB (NF-kappaB) is a candidate marker
      of prostate cancer progression, we tested the association between nuclear
      localization of NF-kappaB in radical prostatectomy specimens and the presence of
      LNI. EXPERIMENTAL DESIGN: NF-kappaB expression in radical prostatectomy specimens
      was assessed with a monoclonal NF-kappaB p65 antibody, in 20 patients with LNI
      and in 31 controls with no LNI and no biochemical relapse 5 years after radical
      prostatectomy. Univariate and multivariate logistic regression models were used.
      The accuracy of multivariate predictions with and without NF-kappaB was
      quantified with the area under the receiver operating characteristics curve and
      200 bootstrap resamples were used to reduce overfit bias. RESULTS: Univariate
      regression models showed a 7% increase in the odds of observing LNI for each 1%
      increase in NF-kappaB nuclear staining (odds ratio, 1.07; P = 0.003). In
      multivariate models, each 1% increase in NF-kappaB was associated with an 8%
      increase in the odds of LNI (odds ratio, 1.08; P = 0.03) and its statistical
      significance was only surpassed by the presence of seminal vesicle invasion (P =
      0.003). Addition of NF-kappaB to all other predictors increased the accuracy of
      LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001). CONCLUSION: This is the
      first study that shows that the extent of nuclear localization of NF-kappaB in
      primary prostate tumors is highly accurately capable of predicting the
      probability of locoregional spread of prostate cancer.

PMID- 17020980
TI  - Identification of alpha-enolase as an autoantigen in lung cancer: its
      overexpression is associated with clinical outcomes.
AB  - PURPOSE: Although existence of humoral immunity has been previously shown in
      malignant pleural effusions, only a limited number of immunogenic tumor
      associated antigens (TAA) have been identified and associated with lung cancer.
      In this study, we intended to identify more TAAs in pleural effusion-derived
      tumor cells. EXPERIMENTAL DESIGN: Using morphologically normal lung tissues as a
      control lysate in Western blotting analyses, 54 tumor samples were screened with
      autologous effusion antibodies. Biochemical purification and mass spectrometric
      identification of TAAs were done using established effusion tumor cell lines as
      antigen sources. We identified a p48 antigen as alpha-enolase (ENO1).
      Semiquantitative immunohistochemistry was used to evaluate expression status of
      ENO1 in the tissue samples of 80 patients with non-small cell lung cancer (NSCLC)
      and then correlated with clinical variables. RESULTS: Using ENO1-specifc
      antiserum, up-regulation of ENO1 expression in effusion tumor cells from 11 of 17
      patients was clearly observed compared with human normal lung primary epithelial
      and non-cancer-associated effusion cells. Immunohistochemical studies
      consistently showed high level of ENO1 expression in all the tumors we have
      examined thus far. Log-rank and Cox's analyses of ENO1 expression status revealed
      that its expression level in primary tumors was a key factor contributing to
      overall- and progression-free survivals of patients (P < 0.05). The same result
      was also obtained in the early stage of NSCLC patients, showing that tumors
      expressing relatively higher ENO1 level were tightly correlated with poorer
      survival outcomes. CONCLUSIONS: Our data strongly support a prognostic role of
      ENO1 in determining tumor malignancy of patients with NSCLC.

PMID- 17020981
TI  - A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered
      intravenously daily for 5 days every 2 weeks to patients with advanced cancer.
AB  - PURPOSE: Patients with advanced cancer received temsirolimus (Torisel, CCI-779),
      a novel inhibitor of mammalian target of rapamycin, i.v. once daily for 5 days
      every 2 weeks to determine the maximum tolerated dose, toxicity profile,
      pharmacokinetics, and preliminary antitumor efficacy. EXPERIMENTAL DESIGN: Doses
      were escalated in successive cohorts of patients using a conventional phase I
      clinical trial design. Samples of whole blood and plasma were collected to
      determine the pharmacokinetics of temsirolimus and sirolimus, its principal
      metabolite. RESULTS: Sixty-three patients were treated with temsirolimus (0.75-24
      mg/m(2)/d). The most common drug-related toxicities were asthenia, mucositis,
      nausea, and cutaneous toxicity. The maximum tolerated dose was 15 mg/m(2)/d for
      patients with extensive prior treatment because, in the 19 mg/m(2)/d cohort, two
      patients had dose-limiting toxicities (one with grade 3 vomiting, diarrhea, and
      asthenia and one with elevated transaminases) and three patients required dose
      reductions. For minimally pretreated patients, in the 24 mg/m(2)/d cohort, one
      patient developed a dose-limiting toxicity of grade 3 stomatitis and two patients
      required dose reductions, establishing 19 mg/m(2)/d as the maximum acceptable
      dose. Immunologic studies did not show any consistent trend toward
      immunosuppression. Temsirolimus exposure increased with dose in a less than
      proportional manner. Terminal half-life was 13 to 25 hours. Sirolimus-to
      temsirolimus exposure ratios were 0.6 to 1.8. A patient with non-small cell lung
      cancer achieved a confirmed partial response, which lasted for 12.7 months. Three
      patients had unconfirmed partial responses; two patients had stable disease for
      >/=24 weeks. CONCLUSION: Temsirolimus was generally well tolerated on this
      intermittent schedule. Encouraging preliminary antitumor activity was observed.

PMID- 17020982
TI  - Analysis of epidermal growth factor receptor gene mutation in patients with non
      small cell lung cancer and acquired resistance to gefitinib.
AB  - PURPOSE: Non-small cell lung cancers carrying activating mutations in the gene
      for the epidermal growth factor receptor (EGFR) are highly sensitive to EGFR
      specific tyrosine kinase inhibitors. However, most patients who initially respond
      subsequently experience disease progression while still on treatment. Part of
      this "acquired resistance" is attributable to a secondary mutation resulting in
      threonine to methionine at codon 790 (T790M) of EGFR. EXPERIMENTAL DESIGN: We
      sequenced exons 18 to 21 of the EGFR gene to look for secondary mutations in
      tumors with acquired resistance to gefitinib in 14 patients with adenocarcinomas.
      Subcloning or cycleave PCR was used in addition to normal sequencing to increase
      the sensitivity of the assay. We also looked for T790M in pretreatment samples
      from 52 patients who were treated with gefitinib. We also looked for secondary
      KRAS gene mutations because tumors with KRAS mutations are generally resistant to
      tyrosine kinase inhibitors. RESULTS: Seven of 14 tumors had a secondary T790M
      mutation. There were no other novel secondary mutations. We detected no T790M
      mutations in pretreatment specimens from available five tumors among these seven
      tumors. Patients with T790M tended to be women, never smokers, and carrying
      deletion mutations, but the T790M was not associated with the duration of
      gefitinib administration. None of the tumors had an acquired mutation in the KRAS
      gene. CONCLUSIONS: A secondary T790M mutation of EGFR accounted for half the
      tumors with acquired resistance to gefitinib in Japanese patients. Other drug
      resistant secondary mutations are uncommon in the EGFR gene.

PMID- 17020983
TI  - Randomized study of paclitaxel and tamoxifen deposition into human brain tumors:
      implications for the treatment of metastatic brain tumors.
AB  - PURPOSE: Drug resistance in brain tumors is partially mediated by the blood-brain
      barrier of which a key component is P-glycoprotein, which is highly expressed in
      cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This
      trial assessed, in primary and metastatic brain tumors, the differential
      deposition of paclitaxel and whether tamoxifen could increase paclitaxel
      deposition. EXPERIMENTAL DESIGN: Patients for surgical resection of their primary
      or metastatic brain tumors were prospectively randomized to prior paclitaxel
      alone (175 mg/m(2)/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central
      and peripheral tumor, surrounding normal brain and plasma, were analyzed for
      paclitaxel and tamoxifen. RESULTS: Twenty-seven patients completed the study.
      Based on a multivariate linear regression model, no significant differences in
      paclitaxel concentrations between the two study arms were found after adjusting
      for treatment group (tamoxifen versus control). However, in analysis for tumor
      type, metastatic brain tumors had higher paclitaxel concentrations in the tumor
      center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039)
      compared with primary brain tumors. Pharmacokinetic analyses showed comparable
      paclitaxel areas under the serum concentration between treatment arms.
      CONCLUSIONS: Paclitaxel deposition was not increased with this tamoxifen schedule
      as the low plasma concentrations were likely secondary to concurrent use of P-450
      inducing medications. However, the statistically higher paclitaxel deposition in
      the periphery of metastatic brain tumors provides functional evidence
      corroborating reports of decreased P-glycoprotein expression in metastatic versus
      primary brain tumors. This suggests that metastatic brain tumors may respond to
      paclitaxel if it has proven clinical efficacy for the primary tumor's
      histopathology.

PMID- 17020984
TI  - Phase I study of decitabine-mediated gene expression in patients with cancers
      involving the lungs, esophagus, or pleura.
AB  - PURPOSE: The DNA methylation paradox, manifested as derepression of cancer-testis
      antigens, and silencing of tumor suppressors during malignant transformation,
      provides the rationale for the utilization of chromatin remodeling agents for
      cancer therapy. A phase I trial was done to examine pharmacokinetics, toxicities,
      and gene expression mediated by 5-aza-2'-deoxycytidine (DAC) in patients with
      thoracic malignancies. EXPERIMENTAL DESIGN: Thirty-five patients with cancers
      refractory to standard therapy received continuous 72-hour DAC infusions using a
      phase I dose-escalation schema. Each full course of therapy consisted of two
      identical 35-day cycles. Plasma DAC levels were evaluated by liquid
      chromatography-mass spectrometry techniques. Quantitative reverse transcription
      PCR, methylation-specific PCR, and immunohistochemical techniques were used to
      evaluate NY-ESO-1, MAGE-3, and p16 expression in tumor biopsies. Long
      oligonucleotide arrays were used to evaluate gene expression profiles in laser
      captured tumor cells before and after DAC exposure. RESULTS: Thirty-five patients
      were evaluable for toxicities; 25 were evaluable for treatment response.
      Myelosuppression constituted dose-limiting toxicity. The maximum tolerated dose
      of DAC was 60 to 75 mg/m(2) depending on the number of prior cytotoxic
      chemotherapy regimens. No objective responses were observed. Plasma DAC
      concentrations approximated thresholds for gene induction in cultured cancer
      cells. Target gene induction was observed in 36% of patients. Posttreatment
      antibodies to NY-ESO-1 were detected in three patients exhibiting NY-ESO-1
      induction in their tumor tissues. Complex, heterogeneous gene expression profiles
      were observed in pretreatment and posttreatment tissues. CONCLUSION: Prolonged
      DAC infusions can modulate gene expression in primary thoracic malignancies.
      These findings support further evaluation of DNA-demethylating agents alone or in
      combination with other regimens targeting induced gene products for the treatment
      of these neoplasms.

PMID- 17020985
TI  - Pharmacogenetic screening of CYP3A and ABCB1 in relation to population
      pharmacokinetics of docetaxel.
AB  - PURPOSE: Despite the extensive clinical experience with docetaxel, unpredictable
      interindividual variability in efficacy and toxicity remain important limitations
      associated with the use of this anticancer drug. Large interindividual
      pharmacokinetic variability has been associated with variation in toxicity
      profiles. Genetic polymorphisms in drug-metabolizing enzymes and drug
      transporters could possibly explain the observed pharmacokinetic variability. The
      aim of this study was therefore to investigate the influence of polymorphisms in
      the CYP3A and ABCB1 genes on the population pharmacokinetics of docetaxel.
      EXPERIMENTAL DESIGN: Whole blood samples were obtained from patients with solid
      tumors and treated with docetaxel to quantify the exposure to docetaxel. DNA was
      collected to determine polymorphisms in the CYP3A and ABCB1 genes with DNA
      sequencing. A population pharmacokinetic analysis of docetaxel was done using
      nonlinear mixed-effect modeling. RESULTS: In total, 92 patients were assessable
      for pharmacokinetic analysis of docetaxel. A three-compartmental model adequately
      described the pharmacokinetics of docetaxel. Several polymorphisms in the CYP3A
      and ABCB1 genes were found, with allele frequencies of 0.54% to 48.4%. The
      homozygous C1236T polymorphism in the ABCB1 gene (ABCB1*8) was significantly
      correlated with a decreased docetaxel clearance (-25%; P = 0.0039). No other
      relationships between polymorphisms and pharmacokinetic variables reached
      statistical significance. Furthermore, no relationship between haplotypes of
      CYP3A and ABCB1 and the pharmacokinetics could be identified. CONCLUSIONS: The
      polymorphism C1236T in the ABCB1 gene was significantly related to docetaxel
      clearance. Our current finding may provide a meaningful tool to explain
      interindividual differences in docetaxel treatment in daily practice.

PMID- 17020986
TI  - Overexpression of caspase-3s splice variant in locally advanced breast carcinoma
      is associated with poor response to neoadjuvant chemotherapy.
AB  - PURPOSE: CASP-3 gene gives rise, by alternative splicing to a caspase-3s variant,
      to the antagonist apoptotic property of caspase-3. Deregulation of splicing in
      tumor cells favoring the expression of antiapoptotic variants has been reported
      to contribute to both tumorigenesis and chemoresistance. Thus, we investigated
      the role of caspase-3 and its splice variant in breast cancer cells. EXPERIMENTAL
      DESIGN: Breast tumor cell lines deficient (MCF-7) and proficient (HBL100) for
      CASP-3 gene were transfected with each transcript and were characterized for
      their apoptotic response to cyclophosphamide. Expression of the two transcripts
      were measured by reverse transcription-PCR in 130 breast carcinomas, including 90
      locally advanced tumors treated with neoadjuvant chemotherapy containing
      cyclophosphamide, epirubicine, and 5-fluorouracil. RESULTS: Overexpression of
      caspase-3s variant in caspase-3-transfected cell lines significantly inhibits
      apoptosis induced by cyclophosphamide (P < 0.0001 for both cell lines). In breast
      tissues, only caspase-3 levels were higher in carcinomas than in corresponding
      adjacent normal tissues (P = 0.0396). Locally advanced carcinomas with high
      levels of caspase-3 (P < 0.0001) and weak levels of caspase-3s (P = 0.0248) were
      more sensitive to treatment. Therefore, increase in caspase-3s/caspase3 ratio
      expression was significantly associated with chemoresistance (P = 0.01). Logistic
      univariate and multivariate analyses realized according to pathologic response
      confirm that increased caspase-3s expression was indicative of chemoresistance (P
      = 0.012 and P = 0.026, respectively). CONCLUSIONS: The results agree with an
      antagonist function between the two transcripts of caspase-3 and show that their
      ratio of expression levels may define a subset of locally advanced breast cancer
      patients who are more likely to benefit from neoadjuvant cyclophosphamide
      containing chemotherapy.

PMID- 17020987
TI  - Intralymphatic dendritic cell vaccination induces tumor antigen-specific, skin
      homing T lymphocytes.
AB  - PURPOSE: The identification of tumor antigens recognized by cytotoxic and T
      helper lymphocytes has led to the development of specific cancer vaccines.
      Immunization with tumor antigen-pulsed dendritic cells has proved effective at
      eliciting elevated levels of tumor antigen-specific T cells in patient blood, but
      objective clinical responses remain rare, suggesting that vaccine-induced T cells
      are not trafficking optimally to site(s) of tumor burden. Accumulating evidence
      from animal models suggests that route of immunization can have a substantial
      influence on the subsequent migration of primed, activated T cells in vivo.
      EXPERIMENTAL DESIGN: In a clinical trial designed to elicit more effective
      cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were
      immunized directly via a peripheral intralymphatic route with autologous
      dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide
      antigens derived from MART-1 and gp100. RESULTS: Within 10 days of intralymphatic
      dendritic cell vaccination, four of six patients developed dramatic and diffuse
      erythematous rashes in sun-exposed areas of skin that showed extensive T-cell
      infiltration. CTLs grown from rash biopsies were strongly enriched for tumor
      antigen-specific T cells that had elevated expression of cutaneous lymphocyte
      antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of
      note, the only patient in the study with cutaneously localized disease showed a
      significant regression of metastatic lesions following the development of a
      surrounding rash. CONCLUSIONS: The evidence presented here is consistent with
      immunization studies in animal models and supports the concept that T cells are
      "imprinted" in peripheral lymph node sites to express specific ligands and
      chemokine receptors that allow them to migrate to skin. Furthermore, the
      preferential migration of the T cells to sun-exposed cutaneous sites suggests
      that inflammation plays a critical role in this migration. These observations
      suggest that further study of the effects of immunization route and inflammation
      on T-cell migration in humans is warranted, and could lead to vaccination
      approaches that would more reliably direct trafficking of activated T cells to
      diverse sites of metastatic disease.

PMID- 17020988
TI  - Phase I study of bryostatin 1 and fludarabine in patients with chronic
      lymphocytic leukemia and indolent (non-Hodgkin's) lymphoma.
AB  - PURPOSE: Preclinical studies suggested that bryostatin 1 might potentiate the
      therapeutic effects of fludarabine in the treatment of hematologic malignancies.
      We undertook a phase I study to identify appropriate schedules and doses of
      bryostatin 1 and fludarabine to be used in phase II studies. EXPERIMENTAL DESIGN:
      Patients with chronic lymphocytic leukemia (CLL) or indolent lymphoma received
      fludarabine daily for 5 days and a single dose of bryostatin 1 via a 24-hour
      continuous infusion either before or after the fludarabine course. Doses were
      escalated in successive patients until recommended phase II doses for each
      sequence were identified on the basis of dose-limiting toxic events. RESULTS:
      Bryostatin 1 can be administered safely and tolerably with full dose fludarabine
      (25 mg/m(2)/d x 5). The recommended bryostatin 1 phase II dose is 50 microg/m(2)
      for both sequences, bryostatin 1 --> fludarabine and fludarabine --> bryostatin
      1. The combination is active against both CLL and indolent lymphomas with
      responses seen in patients who had been previously treated with fludarabine.
      Correlative studies do not support the hypothesis that bryostatin 1 potentiates
      fludarabine activity through down-regulation of protein kinase C in target cells.
      CONCLUSIONS: Bryostatin 1 can be administered with full dose fludarabine, and the
      combination is moderately active in patients with persistent disease following
      prior treatment. In view of the activity of monoclonal antibodies such as the
      anti-CD20 monoclonal antibody rituximab in the treatment of CLL and indolent
      lymphomas, the concept of combining bryostatin 1 and fludarabine with rituximab
      warrants future consideration.

PMID- 17020989
TI  - Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion
      channel protein in the mitochondrial membrane of head and neck squamous cell
      carcinoma: possible role in apoptosis.
AB  - PURPOSE: Cisplatin adducts to nuclear DNA (nDNA) are felt to be the molecular
      lesions that trigger apoptosis, but the mechanism linking nDNA adduct formation
      and cell death is unclear. Some literature in the last decade has suggested a
      possible direct effect of cisplatin on mitochondria independent of nDNA
      interaction. In this study, we define separately the sequelae of cisplatin
      interactions with nDNA and with mitochondria in head and neck squamous cell
      carcinoma (HNSCC) cell lines. EXPERIMENTAL DESIGN: Cisplatin binding to
      mitochondrial DNA (mtDNA) and proteins was analyzed by atomic absorption
      spectroscopy and other methods. RESULTS: Following 1 hour of exposure to
      cisplatin, platinum adducts to mtDNA were 300- to 500-fold more abundant than
      adducts to nDNA; these differences were not due to differences in rates of adduct
      repair. Whereas HNSCC cell cytoplasts free of nDNA retained the same dose
      dependent cisplatin sensitivity as parental cells, HNSCC rho(0) cells free of
      mtDNA were 4- to 5-fold more resistant to cisplatin than parental cells. Isolated
      mitochondria released cytochrome c within minutes of exposure to cisplatin, and
      ultrastructural analysis of intact HNSCC cells by electron microscopy showed
      marked mitochondrial disruption after 4 hours of cisplatin treatment, whereas the
      nucleus and other cellular structures remain intact. The very prompt release of
      cytochrome c from isolated mitochondria implies that apoptosis does not require
      alteration in mitochondrial gene transcription. Further, cisplatin binds
      preferentially to mitochondrial membrane proteins, particularly the voltage
      dependent anion channel. CONCLUSIONS: Cisplatin binding to nDNA is not necessary
      for induction of apoptosis in HNSCC, which can result from direct action of
      cisplatin on mitochondria.

PMID- 17020990
TI  - A mass balance and disposition study of the DNA methyltransferase inhibitor
      zebularine (NSC 309132) and three of its metabolites in mice.
AB  - PURPOSE: To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a
      DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment
      of cancer. EXPERIMENTAL DESIGN: Male, CD(2)F(1) mice were dosed i.v. with 100
      mg/kg 2-[(14)C]zebularine. At specified times between 5 and 1,440 minutes, mice
      were euthanized. Plasma, organs, carcass, urine, and feces were collected and
      assayed for total radioactivity. Plasma and urine were also analyzed for
      zebularine and its metabolites with a previously validated high-pressure liquid
      chromatography assay. A similar experiment was done with 2-[(14)C]uridine, the
      proposed primary metabolite of zebularine. RESULTS: Maximum plasma concentrations
      were 462, 306, 33.6, 21.7, and 11.5 mumol/L for total radioactivity, zebularine,
      uridine, uracil (each at 5 minutes), and dihydrouracil (at 15 minutes),
      respectively. Total radioactivity, zebularine, uridine, uracil, and dihydrouracil
      were rapidly eliminated from plasma, and after 45 minutes, none of the individual
      compounds could be quantitated by high-pressure liquid chromatography. Plasma
      data were consistent with sequential conversion of zebularine to uridine, uracil,
      and dihydrouracil. 2-Pyrimidinone was not observed. Prolonged retention of
      radioactivity, at concentrations higher than in plasma, was observed in tissues.
      Recovery of given radioactivity in urine (30.3% of dose), feces (0.4% of dose),
      cage wash (7.9% of dose), and tissues and carcass (6.1% of dose) after 24 hours
      implied that up to 55% of radioactivity was expired as (14)CO(2). Comparison of
      zebularine and uridine pharmacokinetic data indicated that approximately 40% of
      the zebularine dose was converted to uridine. CONCLUSIONS: Zebularine is
      extensively and rapidly metabolized into endogenous compounds that are unlikely
      to have effects at the concentrations observed.

PMID- 17020991
TI  - Vaccination with viable human umbilical vein endothelial cells prevents
      metastatic tumors by attack on tumor vasculature with both cellular and humoral
      immunity.
AB  - PURPOSE: Because tumor endothelium is rarely targeted by immunity but is
      critically important for tumor growth, the immunity against tumor endothelium is
      to be developed as a novel antitumor strategy. EXPERIMENTAL DESIGN: First, viable
      human umbilical vein endothelial cells (HUVEC) were immunized to C57BL/6 and
      BALB/c mice to evoke specific CTLs as well as antibodies against tumor
      endothelium. Lewis lung carcinoma or myeloma cells were subsequently inoculated
      to evaluate the effect on tumor growth by vaccination. Second, the effect on
      tumor metastasis by vaccination was studied using tumor-resected mice receiving
      HUVEC immunization 3 days after excision. Third, the immune sera and T
      lymphocytes from HUVEC-immunized mice were transferred to tumor-bearing mice and
      added to cultured HUVECs to investigate their antiproliferative effect. RESULTS:
      Viable HUVEC immunization showed potent antitumor effects in Lewis lung carcinoma
      and myeloma tumor models. Both immune sera and CTL inhibited tumor growth and
      specifically suppressed proliferation of HUVECs. Particularly, tumors entirely
      disappeared on day 90 after tumor inoculation in four of six tumor-bearing mice
      receiving CTL therapy. In a metastatic tumor model, we found that the HUVEC
      vaccination prolonged life span from 30.9 to 41.5 days after tumor resection
      compared with PBS-treated mice without apparent side effects. CONCLUSIONS:
      Vaccination with viable HUVECs evoked both humoral and cellular immunity against
      tumor microvasculature, and therefore significantly inhibited tumor growth and
      prolonged life span of tumor-resected mice. This may provide with a novel
      treatment for metastatic tumors. Moreover, we have established a convenient
      method to evoke specific CTL against tumor angiogenesis.

PMID- 17020992
TI  - Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope
      peptides derived from human vascular endothelial growth factor receptor 1.
AB  - PURPOSE: Antiangiogenic therapy is now considered to be one of promising
      approaches to treat various types of cancer. In this study, we examined the
      possibility of developing antiangiogenic cancer vaccine targeting vascular
      endothelial growth factor receptor 1 (VEGFR1) overexpressed on endothelial cells
      of newly formed vessels in the tumor. EXPERIMENTAL DESIGN: Epitope-candidate
      peptides were predicted from the amino acid sequence of VEGFR1 based on their
      theoretical binding affinities to the corresponding HLAs. The A2/Kb transgenic
      mice, which express the alpha1 and alpha2 domains of human HLA-A*0201, were
      immunized with the epitope candidates to examine their effects. We also examined
      whether these peptides could induce human CTLs specific to the target cells in
      vitro. RESULTS: The CTL responses in A2/Kb transgenic mice were induced with
      vaccination using identified epitope peptides restricted to HLA-A*0201. Peptide
      specific CTL clones were also induced in vitro with these identified epitope
      peptides from peripheral blood mononuclear cells donated by healthy volunteers
      with HLA-A*0201. We established CTL clones in vitro from human peripheral blood
      mononuclear cells with HLA-A*2402 as well. These CTL clones were shown to have
      potent cytotoxicities in a HLA class I-restricted manner not only against peptide
      pulsed target cells but also against target cells endogenously expressing VEGFR1.
      Furthermore, immunization of A2/Kb transgenic mice with identified epitope
      peptides restricted to HLA-A*0201 was associated with significant suppression of
      tumor-induced angiogenesis and tumor growth without showing apparent adverse
      effects. CONCLUSIONS: These results strongly suggest that VEGFR1 is a promising
      target for antiangiogenic cancer vaccine and warrants further clinical
      development of this strategy.

PMID- 17020993
TI  - Multiparametric flow cytometric analysis of signal transducer and activator of
      transcription 5 phosphorylation in immune cell subsets in vitro and following
      interleukin-2 immunotherapy.
AB  - PURPOSE: Treatment with interleukin (IL)-2 (Proleukin) yields a 10% to 20%
      response rate in patients with metastatic melanoma or metastatic renal cell
      carcinoma. IL-2 is known to activate distinct signals within lymphocytes,
      including the Janus-activated kinase-signal transducer and activator of
      transcription (STAT) pathway. We examined the phosphorylation of STAT5 (P-STAT5)
      in IL-2-stimulated immune cells of normal subjects and in patients receiving IL-2
      therapy using a novel flow cytometric assay to characterize the pattern and level
      of activation within immune subsets. EXPERIMENTAL DESIGN: Normal peripheral blood
      mononuclear cells (PBMC) were treated in vitro with IL-2 and analyzed for P-STAT5
      using an intracellular flow cytometric assay. PBMC were simultaneously evaluated
      for the induction of STAT5-regulated genes at the transcript level. PBMC were
      also obtained from patients immediately before and 1 hour after treatment with
      high-dose IL-2 and analyzed for the presence of P-STAT5 within immune cell
      subsets by dual-variable intracellular flow cytometry. RESULTS: In vitro IL-2
      treatment produced a rapid and dose-dependent increase in P-STAT5 within normal
      PBMC that correlated with the induction of transcript for the IL-2-responsive
      genes CIS, Pim-1, and SOCS1 (correlation coefficients 0.8628, 0.6667, and 0.7828,
      respectively). Dose-dependent induction of P-STAT5 was detected in PBMC for up to
      18 hours following in vitro pulse stimulation with IL-2. P-STAT5 was detected
      within a subset of normal donor CD4(+) T cells (52.2 +/- 15.0%), CD8(+) T cells
      (57.6 +/- 25.8%), and CD56(+) natural killer (NK) cells (54.2 +/- 27.2%), but not
      CD14(+) monocytes or CD21(+) B cells, following in vitro IL-2 treatment. The
      generation of P-STAT5 within immune cell subsets after the therapeutic
      administration of IL-2 varied significantly between individuals. NK cells were
      noticeably absent in the posttreatment sample, a finding that was consistent for
      all patients examined. Surprisingly, activated STAT5 persisted within CD4(+) and
      CD8(+) T lymphocytes, as well as CD56(+) NK cells, for up to 3 weeks post-IL-2
      treatment in three patients who exhibited a clinical response to therapy and in a
      fourth who exhibited a significant inflammatory response after 11 doses of
      therapy (first cycle). CONCLUSIONS: The flow cytometric assay described herein is
      a highly efficient and reliable method by which to assess the cellular response
      to IL-2 within PBMC and specific immune effector subsets, both in vitro and in
      the clinical setting. Assessment of P-STAT5 in patient PBMC in response to
      therapeutic IL-2 administration reveals disparate responses between immune cell
      subsets as well as interpatient variation. Persistent activation of STAT5 within
      NK and T cells was an unexpected observation and requires further investigation.

PMID- 17020994
TI  - Enhanced antitumor effect of oncolytic adenovirus expressing interleukin-12 and
      B7-1 in an immunocompetent murine model.
AB  - PURPOSE: We investigated whether an armed viral platform, where lytic property of
      a viral infection is coupled to viral-mediated delivery of therapeutic genes,
      could increase the therapeutic potential of a viral-based therapy. EXPERIMENTAL
      DESIGN: We generated interleukin (IL)-12-expressing oncolytic adenovirus (YKL-IL
      12) and IL-12- and B7-1-expressing (YKL-IL12/B7) oncolytic adenovirus.
      Therapeutic efficacy of these newly engineered adenoviruses was then evaluated in
      vivo using an immunocompetent mouse bearing murine melanoma B16-F10 tumors.
      Overall survival was assessed with the Kaplan-Meier method. The induction of
      immune cell cytotoxicity was assessed by CTL assay, IFN-gamma enzyme-linked
      immunospot assay, and immunohistochemical studies. RESULTS: YKL-IL12/B7 oncolytic
      adenovirus, expressing both IL-12 and B7-1, showed a higher incidence of complete
      tumor regression compared with the analogous oncolytic adenovirus, YKL-1, or IL
      12-expressing, YKL-IL12. Significant survival advantage was also seen in response
      to YKL-IL12/B7. Moreover, IL-12 and IFN-gamma levels produced in tumors treated
      with YKL-IL12/B7 was significantly greater than those treated with YKL-IL12. The
      enhanced survival advantage was mediated by the induction of immune cell
      cytotoxicity. In agreement with these results, massive infiltration of CD4(+) and
      CD8(+) T cells into tissues surrounding the necrotic area of the tumor was
      observed following in situ delivery of YKL-IL12/B7. CONCLUSION: Combination of
      oncolysis and the enhancement of antitumor immune response by oncolytic
      adenovirus expressing both IL-12 and B7-1 elicits potent antitumor effect and
      survival advantage.

PMID- 17020995
TI  - Cotreatment with vorinostat (suberoylanilide hydroxamic acid) enhances activity
      of dasatinib (BMS-354825) against imatinib mesylate-sensitive or imatinib
      mesylate-resistant chronic myelogenous leukemia cells.
AB  - PURPOSE: We determined the effects of vorinostat [suberoylanilide hydroxamic acid
      (SAHA)] and/or dasatinib, a dual Abl/Src kinase (tyrosine kinase) inhibitor, on
      the cultured human (K562 and LAMA-84) or primary chronic myelogenous leukemia
      (CML) cells, as well as on the murine pro-B BaF3 cells with ectopic expression of
      the unmutated and kinase domain-mutant forms of Bcr-Abl. EXPERIMENTAL DESIGN:
      Following exposure to dasatinib and/or vorinostat, apoptosis, loss of clonogenic
      survival, as well as the activity and levels of Bcr-Abl and its downstream
      signaling proteins were determined. RESULTS: Treatment with dasatinib attenuated
      the levels of autophosphorylated Bcr-Abl, p-CrkL, phospho-signal transducer and
      activator of transcription 5 (p-STAT5), p-c-Src, and p-Lyn; inhibited the
      activity of Lyn and c-Src; and induced apoptosis of the cultured CML cells.
      Combined treatment of cultured human CML and BaF3 cells with vorinostat and
      dasatinib induced more apoptosis than either agent alone, as well as
      synergistically induced loss of clonogenic survival, which was associated with
      greater depletion of Bcr-Abl, p-CrkL, and p-STAT5 levels. Cotreatment with
      dasatinib and vorinostat also attenuated the levels of Bcr-AblE255K and Bcr
      AblT315I and induced apoptosis of BaF3 cells with ectopic expression of the
      mutant forms of Bcr-Abl. Finally, cotreatment of the primary CML cells with
      vorinostat and dasatinib induced more loss of cell viability and depleted Bcr-Abl
      or Bcr-AblT315I, p-STAT5, and p-CrkL levels than either agent alone. CONCLUSIONS:
      As shown here, the preclinical in vitro activity of vorinostat and dasatinib
      against cultured and primary CML cells supports the in vivo testing of the
      combination in imatinib mesylate-sensitive and imatinib mesylate-resistant CML
      cells.

PMID- 17020996
TI  - Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to
      anthracycline: a role for tumor vascularization.
AB  - PURPOSE: To investigate whether dietary docosahexaenoic acid (DHA), a
      peroxidizable polyunsaturated omega-3 fatty acids, sensitizes rat mammary tumors
      to anthracyclines and whether its action interferes with tumor vascularization, a
      critical determinant of tumor growth. EXPERIMENTAL DESIGN: Female Sprague-Dawley
      rats were initiated by N-methylnitrosourea to develop mammary tumors and then
      assigned to a control group (n = 18), receiving a supplementation of palm oil, or
      to a DHA group (n = 54), supplemented with a microalgae-produced oil (DHASCO, 1.5
      g/d). The DHA group was equally subdivided into three subgroups with addition of
      different amounts of alpha-tocopherol. Epirubicin was injected weekly during 6
      weeks after the largest tumor reached 1.5 cm(2), and subsequent changes in the
      tumor surface were evaluated. Tumor vascularization was assessed by power Doppler
      sonography before and during chemotherapy. RESULTS: DHA and alpha-tocopherol were
      readily absorbed and incorporated into rat tissues. Epirubicin induced a 45%
      mammary tumor regression in the DHA-supplemented group, whereas no tumor
      regression was observed in the control group. In the DHA group, before
      chemotherapy was initiated, tumor vascular density was 43% lower than in the
      control group and remained lower during chemotherapy. Enhancement of epirubicin
      efficacy by DHA was abolished in a dose-dependent manner by alpha-tocopherol, and
      the same trend was observed for DHA-induced reduction in tumor vascular density.
      CONCLUSIONS: Dietary DHA supplementation led to a reduction in tumor
      vascularization before the enhancement of any response to anthracyclines,
      suggesting that DHA chemosensitizes mammary tumors through an inhibition of the
      host vascular response to the tumor.

PMID- 17020997
TI  - MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell
      growth in vitro and in vivo.
AB  - PURPOSE: The purpose of this study is to delineate the biological significance of
      IkappaB kinase (IKK) beta inhibition in multiple myeloma cells in the context of
      bone marrow stromal cells (BMSC) using a novel IKKbeta inhibitor MLN120B.
      EXPERIMENTAL DESIGN: Growth-inhibitory effect of MLN120B in multiple myeloma
      cells in the presence of cytokines [interleukin-6 (IL-6) and insulin-like growth
      factor-I (IGF-1)], conventional agents (dexamethasone, melphalan, and
      doxorubicin), or BMSC was assessed in vitro. In vivo anti-multiple myeloma
      activity of MLN120B was evaluated in severe combined immunodeficient (SCID)-hu
      model. RESULTS: MLN120B inhibits both baseline and tumor necrosis factor-alpha
      induced nuclear factor-kappaB activation, associated with down-regulation of
      IkappaBalpha and p65 nuclear factor-kappaB phosphorylation. MLN120B triggers 25%
      to 90% growth inhibition in a dose-dependent fashion in multiple myeloma cell
      lines and significantly augments tumor necrosis factor-alpha-induced cytotoxicity
      in MM.1S cells. MLN120B augments growth inhibition triggered by doxorubicin and
      melphalan in both RPMI 8226 and IL-6-dependent INA6 cell lines. Neither IL-6 nor
      IGF-1 overcomes the growth-inhibitory effect of MLN120B. MLN120B inhibits
      constitutive IL-6 secretion by BMSCs by 70% to 80% without affecting viability.
      Importantly, MLN120B almost completely blocks stimulation of MM.1S, U266, and
      INA6 cell growth, as well as IL-6 secretion from BMSCs, induced by multiple
      myeloma cell adherence to BMSCs. MLN120B overcomes the protective effect of BMSCs
      against conventional (dexamethasone) therapy. CONCLUSIONS: Our data show that the
      novel IKKbeta inhibitor MLN120B induces growth inhibition of multiple myeloma
      cells in SCID-hu mouse model. These studies provide the framework for clinical
      evaluation of MLN120B, alone and in combined therapies, trials of these novel
      agents to improve patient outcome in multiple myeloma.

PMID- 17020999
TI  - The combination of the rexinoid, LG100268, and a selective estrogen receptor
      modulator, either arzoxifene or acolbifene, synergizes in the prevention and
      treatment of mammary tumors in an estrogen receptor-negative model of breast
      cancer.
AB  - PURPOSE: We tested whether a selective estrogen receptor modulator (SERM) and a
      rexinoid are active for prevention and treatment in the mouse mammary tumor virus
      neu mouse model of estrogen receptor-negative breast cancer. EXPERIMENTAL DESIGN:
      For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz,
      20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination
      for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268
      (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3
      mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment
      studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks.
      RESULTS: The rexinoid 268 and the SERMs Arz and Acol, as individual drugs,
      delayed the development of estrogen receptor-negative tumors. Moreover, the
      combination of a SERM and 268 was strikingly synergistic, as no tumors developed
      in any mouse fed the combination of 268 and a SERM. Moreover, this drug
      combination also induced significant tumor regression when used therapeutically.
      These drugs did not inhibit transgene expression in vitro or in vivo, and the
      combination of Arz and 268 inhibited proliferation and induced apoptosis in the
      tumors. CONCLUSION: The combination of a rexinoid and SERM should be considered
      for future clinical trials.

PMID- 17020998
TI  - Vitamin D inhibits the formation of prostatic intraepithelial neoplasia in
      Nkx3.1;Pten mutant mice.
AB  - PURPOSE: Epidemiologic studies have shown that reduced levels of vitamin D
      represent a major risk factor for prostate cancer. In this report, we have
      examined the efficacy of 1alpha,25-dihydroxyvitamin D(3) (1,25 D(3)) as a
      chemopreventive agent using Nkx3.1; Pten mutant mice, which recapitulate stages
      of prostate carcinogenesis from prostate intraepithelial neoplasia (PIN) to
      adenocarcinoma. EXPERIMENTAL DESIGN: 1,25 D(3) (or vehicle) was delivered
      continuously to Nkx3.1; Pten mutant or control mice for a 4-month period
      beginning before (precancerous cohort) or after (cancerous cohort) these mice
      developed PIN. At the conclusion of the study, the mice were analyzed for the
      occurrence of PIN and/or cancer phenotypes by histologic analyses and
      immunostaining using known markers of cancer progression in these mice. RESULTS:
      We found that sustained delivery of 1,25 D(3) to the Nkx3.1; Pten mutant mice
      resulted in a significant reduction in the formation of PIN while having no
      apparent effect on the control mice. Furthermore, 1,25 D(3) was maximally
      effective when delivered before, rather than subsequent to, the initial
      occurrence of PIN. We further show that this 1,25 D(3)-mediated inhibition of PIN
      was coincident with up-regulation of vitamin D receptor expression in the
      prostatic epithelium of the mutant mice, as well as in CASP prostate epithelial
      cell lines developed from these mice, while having no effect on androgen receptor
      expression or androgen receptor signaling. CONCLUSION: Our findings show the
      value of chemoprevention studies using Nkx3.1; Pten mutant mice, particularly for
      evaluating the efficacy and underlying mechanisms of potential agents and to gain
      insights about the optimal timing of their delivery. In particular, our study
      predicts that vitamin D may have differential effects during early-stage versus
      late-stage disease and that it is more likely to be beneficial if delivered
      either before the overt manifestation of clinically detectable disease or during
      the earliest disease stages, rather than in advanced disease. Thus, our findings
      support the assessment of vitamin D analogues for chemoprevention in clinical
      trials targeting patients with early-stage disease and also establish molecular
      markers that can be used in such trials to determine biological activity and to
      optimize further clinical trials.

PMID- 17021001
TI  - Age determination by magnetic resonance imaging of the wrist in adolescent male
      football players.
AB  - BACKGROUND: In football there are established age-related tournaments for males
      and females to guarantee equal chances within the game for all the different age
      groups. To prevent participation in the incorrect age group, and owing to the
      fact that in some Asian and African countries registration at birth is not
      compulsory, other methods of age determination need to be available. Standard
      radiographs of the left wrist have been used for assessment of skeletal age for
      many years. This is, however, not ethical in the sporting environment. AIM: To
      study the possible use of magnetic resonance imaging (MRI), which has no
      radiation risk, in estimating the age of healthy adolescent football players.
      METHODS: The examination protocol was applied in four countries using, their
      respective MRI equipment using a 1-T or 1.5-T magnet and a wrist coil. 496
      healthy male adolescent football players between the ages of 14 and 19 years from
      Switzerland, Malaysia, Algeria and Argentina were selected for the study. The
      degree of fusion of the left distal radial physis was determined by three
      independent raters by a newly developed grading system which can be used in
      future MRI epiphysial fusion grading studies. RESULTS: The inter-rater
      reliability for grading was high (r = 0.91 and 0.92); all correlations were
      highly significant (p<0.001). The average age increased with a higher grading of
      fusion, and the correlation between age and grade of fusion was highly
      significant (r = 0.69, p<0.001). Only one player (0.8%) in the 16-year-old age
      group was graded as completely fused. CONCLUSION: MRI of the wrist offers an
      alternative as a non-invasive method of age determination in 14-19-year-old male
      adolescents. The grading system presented here clearly identifies the skeletal
      maturity by complete fusion in all MRI slices, which eliminates any risk
      associated with standard radiographic rating as determined by the International
      Atomic Energy Agency.

PMID- 17021000
TI  - Isodeoxyelephantopin, a novel sesquiterpene lactone, potentiates apoptosis,
      inhibits invasion, and abolishes osteoclastogenesis through suppression of
      nuclear factor-kappaB (nf-kappaB) activation and nf-kappaB-regulated gene
      expression.
AB  - PURPOSE: Deoxyelephantopin (ESD) and isodeoxyelephantopin (ESI) are two
      sesquiterpene lactones derived from the medicinal plant Elephantopus scaber Linn.
      (Asteraceae). Although they are used for the treatment of a wide variety of
      proinflammatory diseases, very little is known about their mechanism of action.
      Because most genes that control inflammation are regulated by activation of the
      transcription factor nuclear factor-kappaB (NF-kappaB), we postulated that ESD
      and ESI mediate their activities through modulation of the NF-kappaB activation
      pathway. EXPERIMENTAL DESIGN: We investigated the effect of ESI and ESD on NF
      kappaB activation by electrophoretic mobility shift assay and NF-kappaB-regulated
      gene expression by Western blot analysis. RESULTS: We found that ESI suppressed
      NF-kappaB activation induced by a wide variety of inflammatory agents, including
      tumor necrosis factor (TNF), interleukin-1beta, phorbol 12-myristate 13-acetate,
      and lipopolysaccharide. The suppression was not cell type specific, and both
      inducible and constitutive NF-kappaB activation was blocked. ESI did not
      interfere with the binding of NF-kappaB to DNA but rather inhibited IkappaBalpha
      kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65
      phosphorylation, and subsequent p65 nuclear translocation. ESI also suppressed
      the expression of TNF-induced NF-kappaB-regulated, proliferative, antiapoptotic,
      and metastatic gene products. These effects correlated with enhancement of
      apoptosis induced by TNF and suppression of TNF-induced invasion and receptor
      activator of NF-kappaB ligand-induced osteoclastogenesis. CONCLUSION: Our results
      indicate that ESI inhibits NF-kappaB activation and NF-kappaB-regulated gene
      expression, which may explain the ability of ESI to enhance apoptosis and inhibit
      invasion and osteoclastogenesis.

PMID- 17021002
TI  - Do circulating leucocytes and lymphocyte subtypes increase in response to brief
      exercise in children with and without asthma?
AB  - BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced
      long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways.
      The mechanisms linking exercise and health are not known, but may rest, partly,
      on the ability of exercise to increase circulating immune cells. Little is known
      about the effect of brief exercise, more reflective of naturally occurring
      patterns of physical activity in children, on immune cell responses. OBJECTIVES:
      To determine whether (1) a 6-min bout of exercise can increase circulating
      inflammatory cells in healthy children and (2) the effect of brief exercise is
      greater in children with a history of asthma. METHODS: Children with mild
      moderate persistent asthma and age-matched controls (n = 14 in each group, mean
      age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry
      was performed at baseline and after exercise. Blood was drawn before and after
      exercise, leucocytes were quantified and key lymphocyte cell surface markers were
      assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in
      children with asthma, but increased (p<0.001) most types of leucocytes (eg
      lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma,
      1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl;
      children with asthma, 88 (20) cells/microl)) to the same degree in both groups.
      Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl;
      children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes
      tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+
      RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these
      cell types was found in children with asthma. CONCLUSIONS: Exercise increased
      many circulating inflammatory cells in both children with asthma and controls.
      Circulating inflammatory cells did increase in children with asthma, but not to a
      greater degree than in controls. In fact, basophils and T helper lymphocyte
      memory transition cells did not increase in children with asthma, whereas they
      did increase in controls. Even brief exercise in children and adolescents
      robustly mobilizes circulating immune cells.

PMID- 17021003
TI  - Determining the intensity and energy expenditure during commuter cycling.
AB  - OBJECTIVES: To determine the intensity and energy expenditure during commuter
      cycling, and to investigate whether cycling to work at a self-chosen intensity
      corresponds to recommendations of the Centers for Disease Control and Prevention
      (CDC) and American College of Sports Medicine (ACSM) for health improvement and
      ACSM recommendations for fitness improvement. METHODS: 18 healthy, untrained
      middle-aged people, who did not cycle to work, underwent two maximal exercise
      tests (MT and MT2) in order to measure their maximal heart rate and oxygen
      consumption (VO(2)). MT2 was performed 24 weeks after MT. Participants were asked
      to cycle at least three times a week to their workplace over a one-way minimum
      distance of 2 km. Data on cycling were recorded in a diary. 12 weeks after MT, a
      field test was conducted, where participants had to cycle to or from their
      workplace. The same measurements were taken as during MT as markers of exercise
      intensity. Metabolic equivalents (METs) and energy expenditure were calculated.
      RESULTS: The intensity during the field test was >75% of their maximal aerobic
      capacity. The mean (SD) MET value was 6.8 (1.9). The energy expenditure during
      the field test was 220 (115) kcal or 540 (139) kcal/h and 1539 (892) kcal/week.
      Men consumed significantly (p<0.01) more energy per hour than women. CONCLUSION:
      Commuter cycling at a self-selected intensity meets the CDC and ACSM
      recommendations for health improvement and the ACSM recommendations for
      improvement of cardiorespiratory fitness. However, as the participants cycled
      faster during the field test than during daily cycling, the results should be
      interpreted with caution.

PMID- 17021004
TI  - How do respiratory state and measurement method affect bra size calculations?
AB  - OBJECTIVES: To investigate the effects of respiratory state and measurement
      method on bra size calculation. METHODS: The bra sizes of 16 large-breasted women
      were measured during two respiratory states, end voluntary inspiration and
      relaxed voluntary expiration, and using two sizing methods, which were compared
      against subject-reported bra sizes. RESULTS: Both respiratory state and
      measurement method significantly affected bra size estimations, whereby measuring
      chest circumference during inspiration increased both band and decreased cup
      size. However, whereas bra size calculated using the standard method differed
      significantly from subject-reported bra size, cup size calculated using the
      breast hemi-circumference method did not differ significantly from subject
      reported cup size. CONCLUSIONS: As respiratory state significantly affects bra
      sizes, it should be standardised during bra size measurements. A more valid and
      reliable bra sizing method should be developed, possibly using the breast hemi
      circumference method for cup size estimations and raw under-bust chest
      circumference values for band size.

PMID- 17021007
TI  - Physical activity exercise and cardiovascular health.

PMID- 17021008
TI  - Vulnerability of pulmonary capillaries during severe exercise.

PMID- 17021009
TI  - Gene driven power athletes? Genetic variation in muscular strength and power.

PMID- 17021010
TI  - Spontaneous pneumomediastinum in a marathon runner.
AB  - A previously healthy 19 year old male presented to the emergency department
      complaining of soreness in his neck, difficulty taking a deep breath, and a
      "crinkly feeling" in his neck and upper chest after running a marathon. He was
      diagnosed with spontaneous pneumomediastinum. He did not require any intervention
      or hospitalisation and made a full recovery.

PMID- 17021011
TI  - Heat stroke and 10K "fun runs": new safety measures are called for.

PMID- 17021013
TI  - Coactivator as a target gene specificity determinant for histone H3 lysine 4
      methyltransferases.
AB  - Activating signal cointegrator-2 (ASC-2), a coactivator of multiple transcription
      factors that include retinoic acid receptor (RAR), associates with histone H3-K4
      methyltranferases (H3K4MTs) MLL3 and MLL4 in mixed-lineage leukemia. Here, we
      show that mice expressing a SET domain mutant of MLL3 share phenotypes with
      isogenic ASC2+/- mice and that expression and H3-K4 trimethylation of RAR target
      gene RAR-beta2 are impaired in ASC-2-null mouse embryo fibroblasts (MEFs) or in
      MEFs expressing siRNAs against both MLL3 and MLL4. We also show that MLL3 and
      MLL4 are found in distinct ASC-2-containing complexes rather than in a common ASC
      2 complex, and they are recruited to RAR-beta2 by ASC-2. In contrast, RAR-beta2
      expression is intact in MEFs devoid of menin, a component of MLL1 and MLL2 H3K4MT
      complexes. These results suggest that ASC-2 confers target gene specificity to
      MLL3 and MLL4 H3K4MT complexes and that recruitment of H3K4MTs to their target
      genes generally involves interactions between integral components of H3K4MT
      complexes and transcription factors.

PMID- 17021014
TI  - Artificial evolution extends the spectrum of viruses that are targeted by a
      disease-resistance gene from potato.
AB  - A major class of disease-resistance (R) genes in plants encode nucleotide-binding
      site/leucine-rich repeat (LRR) proteins. The LRR domains mediate recognition of
      pathogen-derived elicitors. Here we describe a random in vitro mutation analysis
      illustrating how mutations in an R protein (Rx) LRR domain generate disease
      resistance specificity. The original Rx protein confers resistance only against a
      subset of potato virus X (PVX) strains, whereas selected mutants were effective
      against an additional strain of PVX and against the distantly related poplar
      mosaic virus. These effects of LRR mutations indicate that in vitro evolution of
      R genes could be exploited for enhancement of disease resistance in crop plants.
      Our results also illustrate how short-term evolution of disease resistance in
      wild populations might be toward broader spectrum resistance against multiple
      strains of the pathogen. The breadth of the disease-resistance phenotype from a
      natural R gene may be influenced by the tradeoff between the costs and benefits
      of broad-spectrum disease resistance.

PMID- 17021015
TI  - Protein complex formation by acetylcholinesterase and the neurotoxin fasciculin-2
      appears to involve an induced-fit mechanism.
AB  - Specific, rapid association of protein complexes is essential for all forms of
      cellular existence. The initial association of two molecules in diffusion
      controlled reactions is often influenced by the electrostatic potential. Yet, the
      detailed binding mechanisms of proteins highly depend on the particular system. A
      complete protein complex formation pathway has been delineated by using
      structural information sampled over the course of the transformation reaction.
      The pathway begins at an encounter complex that is formed by one of the apo forms
      of neurotoxin fasciculin-2 (FAS2) and its high-affinity binding protein,
      acetylcholinesterase (AChE), followed by rapid conformational rearrangements into
      an intermediate complex that subsequently converts to the final complex as
      observed in crystal structures. Formation of the intermediate complex has also
      been independently captured in a separate 20-ns molecular dynamics simulation of
      the encounter complex. Conformational transitions between the apo and liganded
      states of FAS2 in the presence and absence of AChE are described in terms of
      their relative free energy profiles that link these two states. The transitions
      of FAS2 after binding to AChE are significantly faster than in the absence of
      AChE; the energy barrier between the two conformational states is reduced by
      half. Conformational rearrangements of FAS2 to the final liganded form not only
      bring the FAS2/AChE complex to lower energy states, but by controlling transient
      motions that lead to opening or closing one of the alternative passages to the
      active site of the enzyme also maximize the ligand's inhibition of the enzyme.

PMID- 17021016
TI  - Diacylglycerol kinase delta regulates protein kinase C and epidermal growth
      factor receptor signaling.
AB  - Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate its
      signaling. To study DGKdelta, we disrupted its gene in mice and found that
      DGKdelta deficiency reduced EGF receptor (EGFR) protein expression and activity.
      Similar to EGFR knockout mice, DGKdelta-deficient pups were born with open
      eyelids and died shortly after birth. PKCs are activated by DAG and phosphorylate
      EGFR to reduce its expression and activity. We found DAG accumulation, increased
      threonine phosphorylation of EGFR, enhanced phosphorylation of other PKC
      substrates, and increased PKC autophosphorylation in DGKdelta knockout cells,
      indicating that DGKdelta regulates EGFR by modulating PKC signaling.

PMID- 17021017
TI  - Epizootics of wild fish induced by farm fish.
AB  - The continuing decline of ocean fisheries and rise of global fish consumption has
      driven aquaculture growth by 10% annually over the last decade. The association
      of fish farms with disease emergence in sympatric wild fish stocks remains one of
      the most controversial and unresolved threats aquaculture poses to coastal
      ecosystems and fisheries. We report a comprehensive analysis of the spread and
      impact of farm-origin parasites on the survival of wild fish populations. We
      mathematically coupled extensive data sets of native parasitic sea lice
      (Lepeophtheirus salmonis) transmission and pathogenicity on migratory wild
      juvenile pink (Oncorhynchus gorbuscha) and chum (Oncorhynchus keta) salmon. Farm
      origin lice induced 9-95% mortality in several sympatric wild juvenile pink and
      chum salmon populations. The epizootics arise through a mechanism that is new to
      our understanding of emerging infectious diseases: fish farms undermine a
      functional role of host migration in protecting juvenile hosts from parasites
      associated with adult hosts. Although the migratory life cycles of Pacific salmon
      naturally separate adults from juveniles, fish farms provide L. salmonis novel
      access to juvenile hosts, in this case raising infection rates for at least the
      first approximately 2.5 months of the salmon's marine life (approximately 80 km
      of the migration route). Spatial segregation between juveniles and adults is
      common among temperate marine fishes, and as aquaculture continues its rapid
      growth, this disease mechanism may challenge the sustainability of coastal
      ecosystems and economies.

PMID- 17021018
TI  - Responses of neurons in the medial superior temporal visual area to apparent
      motion stimuli in macaque monkeys.
AB  - Monkeys fixated a stationary spot during presentation of dot textures that moved
      in apparent motion defined by the spatial and temporal separations, Deltax and
      Deltat, between successive flashes of each dot. For each neuron, we assessed the
      speed tuning for smooth motion (Deltat = 2 or 4 ms) at speeds < or =128 degrees
      /s and the effect of varying the value of Deltat at speeds of 16 and 32 degrees
      /s. Many medial superior temporal (MST) neurons, like middle temporal (MT)
      neurons, were tuned for the speed of smooth motion and showed decreases in firing
      rate as the value of Deltat increased at a constant speed. A subset of MST
      neurons, however, showed monotonically increasing firing rates as a function of
      smooth stimulus speed and responses to apparent motion that paralleled a
      previously discovered illusion where estimates of target speed increase with the
      value of Deltat. Opponent firing rate, defined as the difference between
      responses for motion in the preferred and opposite directions, peaked at values
      of Deltat that were consistent with the behavioral illusion. Comparison with a
      new sample of MT neurons recorded with the same stimuli failed to reveal
      comparable effects. Attempts to map the population responses in MT and MST onto
      the behavioral illusion of increased speed succeeded by averaging the opponent
      response across MST neurons, but only by applying vector averaging to determine
      the preferred speed of the most active MT neurons. We suggest that a vector
      averaging computation transforms MT's place code for target speed into the rate
      code of some MST neurons.

PMID- 17021019
TI  - Temporal development of asymmetric reward-induced bias in macaques.
AB  - Time and expected outcome are two ubiquitous factors contributing to decision
      making. However, it is unclear how they interact to influence motor responses.
      When two differential reward outcomes are expected at the end of a waiting
      period, behavioral bias is consistently induced, manifested as shorter latencies
      for motor responses associated with the preferred reward. To examine how this
      bias develops in time during the waiting period, we manipulated the duration of
      the waiting period in an asymmetric reward saccade task in monkeys. We found that
      the bias increases with the duration of waiting period. Surprisingly, the bias
      resulted from gradual suppression of saccades to nonpreferred targets rather than
      from facilitation of saccades to preferred targets. These results have important
      implications on the neural correlates of reward-induced bias.

PMID- 17021020
TI  - Dynamics of receptive field size in primary visual cortex.
AB  - Recent studies have shown that the initial responses evoked by a stimulus in
      neurons of primary visual cortex are dominated by low spatial frequency
      information in the image, whereas finer spatial scales dominate later in the
      response. Such phenomena could arise from the dynamics of receptive field (RF)
      size at early stages of cortical processing. We measured changes in RF size in
      simple cells recorded from the primary visual cortex of anesthetized macaques by
      measuring their first-order spatio-temporal kernels and fitting them with two
      dimensional Gabor functions at different time slices. We found that the width and
      length of the RF envelope and the period of the carrier tend to decrease during
      the time-course of the response. The most pronounced changes are seen in the
      width and spatial period of the RFs, which decrease by 15% during the central 20
      ms of the response. These results show a novel form of spatio-temporal
      inseparability in simple cells and are consistent with the notion of a coarse-to
      fine processing of information in early visual cortex.

PMID- 17021021
TI  - Glucocorticoids specifically enhance L-type calcium current amplitude and affect
      calcium channel subunit expression in the mouse hippocampus.
AB  - Previous studies have shown that corticosterone enhances whole cell calcium
      currents in CA1 pyramidal neurons, through a pathway involving binding of
      glucocorticoid receptor homodimers to the DNA. We examined whether
      glucocorticoids show selectivity for L- over N-type of calcium currents.
      Moreover, we addressed the putative gene targets that eventually lead to the
      enhanced calcium currents. Electrophysiological recordings were performed in
      nucleated patches that allow excellent voltage control. Calcium currents in these
      patches almost exclusively involve N- and L-type channels. We found that L- but
      not N-type calcium currents were largely enhanced after treatment with a high
      dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage
      dependency and kinetic properties of the currents were unaffected by the hormone.
      Nonstationary noise analysis suggests that the increased current is not caused by
      a larger unitary conductance, but rather to a doubling of the number of
      functional channels. Quantitative real-time PCR revealed that transcripts of the
      Ca(v)1 subunits encoding for the N- or L-type calcium channels are not
      upregulated in the mouse CA1 area; instead, a strong, direct, and consistent
      upregulation of the beta4 subunit was observed. This indicates that the
      corticosteroid-induced increase in number of L-type calcium channels is not
      caused by a simple transcriptional regulation of the pore-forming subunit of the
      channels.

PMID- 17021022
TI  - Spatial representation of neural responses to natural and altered conspecific
      vocalizations in cat auditory cortex.
AB  - This study shows the neural representation of cat vocalizations, natural and
      altered with respect to carrier and envelope, as well as time-reversed, in four
      different areas of the auditory cortex. Multiunit activity recorded in primary
      auditory cortex (AI) of anesthetized cats mainly occurred at onsets (<200-ms
      latency) and at subsequent major peaks of the vocalization envelope and was
      significantly inhibited during the stationary course of the stimuli. The first
      200 ms of processing appears crucial for discrimination of a vocalization in AI.
      The dorsal and ventral parts of AI appear to have different roles in coding
      vocalizations. The dorsal part potentially discriminated carrier-altered meows,
      whereas the ventral part showed differences primarily in its response to natural
      and time-reversed meows. In the posterior auditory field, the different temporal
      response types of neurons, as determined by their poststimulus time histograms,
      showed discrimination for carrier alterations in the meow. Sustained firing
      neurons in the posterior ectosylvian gyrus (EP) could discriminate, among others,
      by neural synchrony, temporal envelope alterations of the meow, and time
      reversion thereof. These findings suggest an important role of EP in the
      detection of information conveyed by the alterations of vocalizations.
      Discrimination of the neural responses to different alterations of vocalizations
      could be based on either firing rate, type of temporal response, or neural
      synchrony, suggesting that all these are likely simultaneously used in processing
      of natural and altered conspecific vocalizations.

PMID- 17021023
TI  - Perceptual correlate of nociceptive long-term potentiation (LTP) in humans shares
      the time course of early-LTP.
AB  - As in neocortex and hippocampus, neurons in the dorsal horn of the spinal cord
      develop long-term potentiation of synaptic efficacy (LTP) on high-frequency
      stimulation (HFS) of their afferent input, although how long LTP lasts in this
      nociceptive relay nucleus has not yet been addressed. Here we studied neurogenic
      hyperalgesia, a perceptual correlate of nociceptive LTP, in 13 healthy subjects,
      after HFS (5 x 1 s at 100 Hz) of superficial cutaneous afferents. HFS led to a
      mean upward shift of the stimulus-response function for pinprick-evoked pain
      (punctate mechanical hyperalgesia) in all subjects by a factor of 2.5 (P < 0.001)
      that lasted undiminished for the initial 1-h observation period. Follow-up tests
      until the next day revealed that this type of neurogenic hyperalgesia decayed
      with a t(1/2) of 3.3 h (99% CI: 3.1-3.5 h) and disappeared completely within 25.4
      h (99% CI: 20.4-31.6 h). Touch-evoked pain (dynamic mechanical allodynia)
      developed in eight of 13 subjects, decayed with a t(1/2) of 2.9 h from the
      maximum and disappeared within 9.3 h. These findings suggest that a single HFS
      session induces nociceptive LTP in healthy subjects that corresponds to early-LTP
      (LTP1), implying primarily posttranslational mechanisms for this type of
      plasticity of human pain perception.

PMID- 17021024
TI  - Firing patterns of human genioglossus motor units during voluntary tongue
      movement.
AB  - The tongue participates in a range of complex oromotor behaviors, including
      mastication, swallowing, respiration, and speech. Previous electromyographic
      studies of the human tongue have focused on respiratory-related tongue muscle
      activities and their role in maintaining upper airway patency. Remarkably, the
      activities of human hypoglossal motor units have not been studied during the
      execution of voluntary maneuvers. We recorded single motor unit activity using
      tungsten microelectrodes in the genioglossus muscle of 10 healthy human subjects
      performing both slow tongue protrusions and a static holding maneuver.
      Displacement of the tongue was detected by an isotonic transducer coupled to the
      lingual surface through a customized lever arm. For protrusion trials, the firing
      rate at recruitment was 13.1 +/- 3 Hz and increased steeply to an average of 24
      +/- 6 Hz, often with very modest increases in tongue protrusion. For the static
      holding task, the average firing rate was 16.1 +/- 4 Hz, which is surprisingly
      high relative to limb motor units. The average coefficient of variation of
      interspike intervals was approximately 20% (range, 10-28%). These are the first
      recordings of their type obtained in human subjects and provide an initial
      glimpse into the voluntary control of hypoglossal motoneurons during tongue
      movements presumably instigated by activity in the motor cortex.

PMID- 17021025
TI  - Neural averaging in motor learning.
AB  - The capacity for skill development over multiple training episodes is fundamental
      to human motor function. We have studied the process by which skills evolve with
      training by progressively modifying a series of motor learning tasks that
      subjects performed over a 1-mo period. In a series of empirical and modeling
      studies, we show that performance undergoes repeated modification with new
      learning. Each in a series of prior training episodes contributes such that
      present performance reflects a weighted average of previous learning. Moreover,
      we have observed that the relative weighting of skills learned wholly in the past
      changes with time. This suggests that the neural substrate of skill undergoes
      modification after consolidation.

PMID- 17021026
TI  - Neural control and coordination of jumping in froghopper insects.
AB  - The thrust for jumping in froghopper insects is produced by a rapid, synchronous
      depression of both hind legs generated by huge, multipartite trochanteral
      depressor muscles in the thorax and smaller levator muscles in the coxae. A three
      phase motor pattern activates these muscles in jumping. First, a levation phase
      lasts a few hundred milliseconds, in which a burst of spikes in the trochanteral
      levator motor neurons moves the hind legs into their fully cocked position and
      thus engages a mechanical lock between a coxa and a femur. Second, a cocked phase
      lasts a few seconds, in which a trochanteral depressor motor neuron spikes
      continuously at a frequency gradually rising to 50 Hz, although the hind legs
      remain stationary. Levator motor spikes are sporadic. Third, the jump movement
      lasts <1 ms, in which the spikes in the depressors stop abruptly and the legs
      rapidly depress. This pattern may vary in the speed of the initial levation and
      in the duration of the cocked phase. Recordings from the depressor muscles on
      both sides showed remarkable synchrony of their motor spikes. In one 4.9-long
      cocked phase all 174 spikes were synchronous and in another 27 s period of
      continuous spiking all but one of 1,176 spikes were synchronous. When a single
      hind leg moves rapidly, these depressor spikes are nevertheless independent of
      those of the other leg. These features of the motor pattern and the coupling
      between motor neurons to the two hind legs ensure powerful movements to propel
      rapid jumping.

PMID- 17021027
TI  - Modulation of cellular and synaptic variability in the lamprey spinal cord.
AB  - Variability is increasingly recognized as a characteristic feature of cellular,
      synaptic, and network properties. While studies have traditionally focused on
      mean values, significant effects can result from changes in variance. This study
      has examined cellular and synaptic variability in the lamprey spinal cord and its
      modulation by the neuropeptide substance P. Cellular and synaptic variability
      differed in different types of cell and synapse. Substance P reduced the
      variability of subthreshold locomotor-related depolarizations and spiking in
      motor neurons during network activity. These effects were associated with a
      reduction in the variability of spiking in glutamatergic excitatory network
      interneurons and with a reduction in the variance of excitatory interneuron
      evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the
      variance of postsynpatic potentials (PSPs) from crossing inhibitory and
      excitatory interneurons, but it increased the variance of inhibitory postsynpatic
      potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the
      variance of different PSPs could occur with or without changes in the PSP
      amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs
      was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The
      NMDA dependence suggested that substance P was acting postsynaptically. This was
      supported by the reduced variability of postsynaptic responses to glutamate by
      substance P. However, ultrastructural analyses suggested that there may also be a
      presynaptic component to the modulation, because substance P reduced the
      variability of synaptic vesicle diameters in putative glutamatergic terminals.
      These results suggest that cellular and synaptic variability can be targeted for
      modulation, making it an additional source of spinal cord plasticity.

PMID- 17021028
TI  - Correlations between the same motor cortex cells and arm muscles during a trained
      task, free behavior, and natural sleep in the macaque monkey.
AB  - Traditionally, the neural control of movement has been studied by recording cell
      activity in restrained animals performing repetitive, highly trained tasks within
      a restricted workspace. However, the degree to which results obtained under these
      conditions are valid during natural, unconstrained behavior remains unknown.
      Using an autonomous, implantable recording system, we examined the relationships
      between the firing of motor cortex cells and forearm muscle activity in primates
      under three behavioral conditions: performance of a conventional torque-tracking
      task, unrestrained behavior, and natural sleep. We found strong correlations over
      long periods of daytime activity, suggesting a consistent relationship between
      cortex and muscles across the repertoire of awake behavior. The range of
      correlation values was comparable during task performance, but many individual
      cells exhibited significant differences across conditions. During the night,
      phases of sleep were associated with a cyclical pattern of cell and muscle
      activity. Across the population, the strength of cell-muscle correlations was
      related to preferred direction for daytime but not nighttime activity. The
      relationship of cells to behavior remained consistent over periods of several
      weeks. These findings extend the interpretation of results obtained under
      constrained conditions and are relevant to the development of neural prostheses
      for restoring natural movements to patients with motor deficits.

PMID- 17021029
TI  - Dissociation of dorsal root ganglion neurons induces hyperexcitability that is
      maintained by increased responsiveness to cAMP and cGMP.
AB  - Injury or inflammation affecting sensory neurons in dorsal root ganglia (DRG)
      causes hyperexcitability of DRG neurons that can lead to spontaneous firing and
      neuropathic pain. Recent results indicate that after chronic compression of DRG
      (CCD treatment), both hyperexcitability of neurons in intact DRG and behaviorally
      expressed hyperalgesia are maintained by concurrent activity in cAMP-protein
      kinase A (PKA) and cGMP-protein kinase G (PKG) signaling pathways. We report here
      that when tested under identical conditions, dissociation produces a pattern of
      hyperexcitability in small DRG neurons similar to that produced by CCD treatment,
      manifest as decreased action potential (AP) current threshold, increased AP
      duration, increased repetitive firing to depolarizing pulses, increased
      spontaneous firing and resting depolarization. A novel feature of this
      hyperexcitability is its early expression-as soon as testing can be conducted
      after dissociation (approximately 2 h). Both forms of injury increase the
      electrophysiological responsiveness of the neurons to activation of cAMP-PKA and
      cGMP-PKG pathways as indicated by enhancement of hyperexcitability by agonists of
      these pathways in dissociated or CCD-treated neurons but not in control neurons.
      Although inflammatory signals are known to activate cAMP-PKA pathways,
      dissociation-induced hyperexcitability is unlikely to be triggered by signals
      released from inflammatory cells recruited to the DRG because of insufficient
      time for recruitment during the dissociation procedure. Inhibition by specific
      antagonists indicates that continuing activation of cAMP-PKA and cGMP-PKG
      pathways is required to maintain hyperexcitability after dissociation. The
      reduction of hyperexcitability by blockers of adenylyl cyclase and soluble
      guanylyl cyclase after dissociation suggests a continuing release of autocrine
      and/or paracrine factors from dissociated neurons and/or satellite cells, which
      activate both cyclases and help to maintain acute, injury-induced
      hyperexcitability of DRG neurons.

PMID- 17021030
TI  - Beta-subunit-dependent modulation of hSlo BK current by arachidonic acid.
AB  - In this study, we examined the effect of arachidonic acid (AA) on the BK alpha
      subunit with or without beta-subunits expressed in Xenopus oocytes. In excised
      patches, AA potentiated the hSlo-alpha current and slowed inactivation only when
      beta2/3 subunit was co-expressed. The beta2-subunit-dependent modulation by AA
      persisted in the presence of either superoxide dismutase or inhibitors of AA
      metabolism such as nordihydroguaiaretic acid and eicosatetraynoic acid,
      suggesting that AA acts directly rather than through its metabolites. Other cis
      unsaturated fatty acids (docosahexaenoic and oleic acid) also enhanced hSlo-alpha
      + beta2 currents and slowed inactivation, whereas saturated fatty acids
      (palmitic, stearic, and caprylic acid) were without effect. Pretreatment with
      trypsin to remove the cytosolic inactivation domain largely occluded AA action.
      Intracellularly applied free synthetic beta2-ball peptide induced inactivation of
      the hSlo-alpha current, and AA failed to enhance this current and slow the
      inactivation. These results suggest that AA removes inactivation by interacting,
      possibly through conformational changes, with beta2 to prevent the inactivation
      ball from reaching its receptor. Our data reveal a novel mechanism of beta
      subunit-dependent modulation of BK channels by AA. In freshly dissociated mouse
      neocortical neurons, AA eliminated a transient component of whole cell K(+)
      currents. BK channel inactivation may be a specific mechanism by which AA and
      other unsaturated fatty acids influence neuronal death/survival in
      neuropathological conditions.

PMID- 17021031
TI  - Influence of electrotonic structure and synaptic mapping on the receptive field
      properties of a collision-detecting neuron.
AB  - The lobula giant movement detector (LGMD) is a visual interneuron of Orthopteran
      insects involved in collision avoidance and escape behavior. The LGMD possesses a
      large dendritic field thought to receive excitatory, retinotopic projections from
      the entire compound eye. We investigated whether the LGMD's receptive field for
      local motion stimuli can be explained by its electrotonic structure and the eye's
      anisotropic sampling of visual space. Five locust (Schistocerca americana) LGMD
      neurons were stained and reconstructed. We show that the excitatory dendritic
      field and eye can be fitted by ellipsoids having similar geometries. A passive
      compartmental model fit to electrophysiological data was used to demonstrate that
      the LGMD is not electrotonically compact. We derived a spike rate to membrane
      potential transform using intracellular recordings under visual stimulation,
      allowing direct comparison between experimental and simulated receptive field
      properties. By assuming a retinotopic mapping giving equal weight to each
      ommatidium and equally spaced synapses, the model reproduced the experimental
      data along the eye equator, though it failed to reproduce the receptive field
      along the ventral-dorsal axis. Our results illustrate how interactions between
      the distribution of synaptic inputs and the electrotonic properties of neurons
      contribute to shaping their receptive fields.

PMID- 17021032
TI  - A stochastic framework for evaluating seizure prediction algorithms using hidden
      Markov models.
AB  - Responsive, implantable stimulation devices to treat epilepsy are now in clinical
      trials. New evidence suggests that these devices may be more effective when they
      deliver therapy before seizure onset. Despite years of effort, prospective
      seizure prediction, which could improve device performance, remains elusive. In
      large part, this is explained by lack of agreement on a statistical framework for
      modeling seizure generation and a method for validating algorithm performance. We
      present a novel stochastic framework based on a three-state hidden Markov model
      (HMM) (representing interictal, preictal, and seizure states) with the feature
      that periods of increased seizure probability can transition back to the
      interictal state. This notion reflects clinical experience and may enhance
      interpretation of published seizure prediction studies. Our model accommodates
      clipped EEG segments and formalizes intuitive notions regarding statistical
      validation. We derive equations for type I and type II errors as a function of
      the number of seizures, duration of interictal data, and prediction horizon
      length and we demonstrate the model's utility with a novel seizure detection
      algorithm that appeared to predicted seizure onset. We propose this framework as
      a vital tool for designing and validating prediction algorithms and for
      facilitating collaborative research in this area.

PMID- 17021033
TI  - Comparison of shape encoding in primate dorsal and ventral visual pathways.
AB  - Ventral and dorsal visual pathways perform fundamentally different functions. The
      former is involved in object recognition, whereas the latter carries out spatial
      localization of stimuli and visual guidance of motor actions. Despite the
      association of the dorsal pathway with spatial vision, recent studies have
      reported shape selectivity in the dorsal stream. We compared shape encoding in
      anterior inferotemporal cortex (AIT), a high-level ventral area, with that in
      lateral intraparietal cortex (LIP), a high-level dorsal area, during a fixation
      task. We found shape selectivities of individual neurons to be greater in
      anterior inferotemporal cortex than in lateral intraparietal cortex. At the
      neural population level, responses to different shapes were more dissimilar in
      AIT than LIP. Both observations suggest a greater capacity in AIT for making
      finer shape distinctions. Multivariate analyses of AIT data grouped together
      similar shapes based on neural population responses, whereas such grouping was
      indistinct in LIP. Thus in a first comparison of shape response properties in
      late stages of the two visual pathways, we report that AIT exhibits greater
      capability than LIP for both object discrimination and generalization. These
      differences in the two visual pathways provide the first neurophysiological
      evidence that shape encoding in the dorsal pathway is distinct from and not a
      mere duplication of that formed in the ventral pathway. In addition to shape
      selectivity, we observed stimulus-driven cognitive effects in both areas.
      Stimulus repetition suppression in LIP was similar to the well-known repetition
      suppression in AIT and may be associated with the "inhibition of return" memory
      effect observed during reflexive attention.

PMID- 17021034
TI  - Profilin is an effector for Daam1 in non-canonical Wnt signaling and is required
      for vertebrate gastrulation.
AB  - Non-canonical Wnt signaling plays important roles during vertebrate embryogenesis
      and is required for cell motility during gastrulation. However, the molecular
      mechanisms of how Wnt signaling regulates modification of the actin cytoskeleton
      remain incompletely understood. We had previously identified the Formin homology
      protein Daam1 as an important link between Dishevelled and the Rho GTPase for
      cytoskeletal modulation. Here, we report that Profilin1 is an effector downstream
      of Daam1 required for cytoskeletal changes. Profilin1 interacted with the FH1
      domain of Daam1 and was localized with Daam1 to actin stress fibers in response
      to Wnt signaling in mammalian cells. In addition, depletion of Profilin1
      inhibited stress fiber formation induced by non-canonical Wnt signaling.
      Inhibition or depletion of Profilin1 in vivo specifically inhibited blastopore
      closure in Xenopus but did not affect convergent extension movements, tissue
      separation or neural fold closure. Our studies define a molecular pathway
      downstream of Daam1 that controls Wnt-mediated cytoskeletal reorganization for a
      specific morphogenetic process during vertebrate gastrulation.

PMID- 17021035
TI  - Cholangiocyte marker-positive and -negative fetal liver cells differ
      significantly in their ability to regenerate the livers of adult rats exposed to
      retrorsine.
AB  - We have used monoclonal antibodies against cell-surface developmental epitopes in
      combination with micromagnetic beads to isolate phenotypically defined
      subpopulations of cholangiocyte marker-positive fetal liver epithelial cells (CMP
      FLEC). Differentiation potential was evaluated by injecting cell isolates from
      dipeptidyl peptidase IV (DPPIV) positive (DPPIV+) Fischer donor rats into the
      spleen of partially hepatectomized, DPPIV negative (DPPIV-) Fischer host rats
      exposed to retrorsine. At various time points, liver tissue was harvested and
      cells in DPPIV+ colonies were phenotyped by immunofluorescence and histochemical
      protocols. Functional differentiation and liver replacement were determined by
      comparing donor and host hepatocyte protein expression patterns and DPPIV enzyme
      activity in extracts from livers of host rats receiving CMP-FLEC. Our results
      showed that bipotentiality was retained during differentiation and maturation of
      CMP-FLEC, indicating that the acquisition of ductal morphology and phenotype were
      not indicative of lineage commitment. CMP-FLEC transplanted into the adult rat
      liver lost ductal and gained hepatocyte markers, and acquired protein expression
      patterns in 2D gels with a close similarity (>75% spot match) to host hepatocytes
      but differing significantly from the transplanted CMP-FLEC cell isolate (<25%
      spot match). The average size of donor hepatocyte colonies increased with time so
      that by 1 year, up to 70% of the host rat liver was replaced by CMP-FLEC derived
      DPPIV+ hepatocytes. Depletion of CMP-FLEC from fetal liver isolates resulted in a
      marked decrease in adult liver colonization, suggesting that a high percentage of
      the hepatocyte colonies in animals receiving total fetal liver isolates are
      derived from CMP-FLEC.

PMID- 17021036
TI  - COUP-TFI is required for the formation of commissural projections in the
      forebrain by regulating axonal growth.
AB  - The transcription factor COUP-TFI (NR2F1), an orphan member of the nuclear
      receptor superfamily, is an important regulator of neurogenesis, cellular
      differentiation and cell migration. In the forebrain, COUP-TFI controls the
      connectivity between thalamus and cortex and neuronal tangential migration in the
      basal telencephalon. Here, we show that COUP-TFI is required for proper axonal
      growth and guidance of all major forebrain commissures. Fibres of the corpus
      callosum, the hippocampal commissure and the anterior commissure project
      aberrantly and fail to cross the midline in COUP-TFI null mutants. Moreover,
      hippocampal neurons lacking COUP-TFI have a defect in neurite outgrowth and show
      an abnormal axonal morphology. To search for downstream effectors, we used
      microarray analysis and showed that, in the absence of COUP-TFI, expression of
      various cytoskeleton molecules involved in neuronal morphogenesis is affected.
      Diminished protein levels of the microtubule-associated protein MAP1B and
      increased levels of the GTP-binding protein RND2 were confirmed in the developing
      cortex in vivo and in primary hippocampal neurons in vitro. Therefore, based on
      morphological studies, gene expression profiling and primary cultured neurons,
      the present data uncover a previously unappreciated intrinsic role for COUP-TFI
      in axonal growth in vivo and supply one of the premises for COUP-TFI coordination
      of neuronal morphogenesis in the developing forebrain.

PMID- 17021037
TI  - Compartmentalisation of Rho regulators directs cell invagination during tissue
      morphogenesis.
AB  - During development, small RhoGTPases control the precise cell shape changes and
      movements that underlie morphogenesis. Their activity must be tightly regulated
      in time and space, but little is known about how Rho regulators (RhoGEFs and
      RhoGAPs) perform this function in the embryo. Taking advantage of a new probe
      that allows the visualisation of small RhoGTPase activity in Drosophila, we
      present evidence that Rho1 is apically activated and essential for epithelial
      cell invagination, a common morphogenetic movement during embryogenesis. In the
      posterior spiracles of the fly embryo, this asymmetric activation is achieved by
      at least two mechanisms: the apical enrichment of Rho1; and the opposing
      distribution of Rho activators and inhibitors to distinct compartments of the
      cell membrane. At least two Rho1 activators, RhoGEF2 and RhoGEF64C are localised
      apically, whereas the Rho inhibitor RhoGAP Cv-c localises at the basolateral
      membrane. Furthermore, the mRNA of RhoGEF64C is also apically enriched, depending
      on signals present within its open reading frame, suggesting that apical
      transport of RhoGEF mRNA followed by local translation is a mechanism to
      spatially restrict Rho1 activity during epithelial cell invagination.

PMID- 17021038
TI  - The puromycin-sensitive aminopeptidase PAM-1 is required for meiotic exit and
      anteroposterior polarity in the one-cell Caenorhabditis elegans embryo.
AB  - In the nematode Caenorhabditis elegans, sperm entry into the oocyte triggers the
      completion of meiosis and the establishment of the embryonic anteroposterior (AP)
      axis. How the early embryo makes the transition from a meiotic to a mitotic
      zygote and coordinates cell cycle changes with axis formation remains unclear. We
      have discovered roles for the C. elegans puromycin-sensitive aminopeptidase PAM-1
      in both cell cycle progression and AP axis formation, further implicating
      proteolytic regulation in these processes. pam-1 mutant embryos exhibit a delay
      in exit from meiosis: thus, this peptidase is required for progression to mitotic
      interphase. In addition, the centrosomes associated with the sperm pronucleus
      fail to closely associate with the posterior cortex in pam-1 mutants, and the AP
      axis is not specified. The meiotic exit and polarity defects are separable, as
      inactivation of the B-type cyclin CYB-3 in pam-1 mutants rescues the meiotic exit
      delay but not the polarity defects. Thus PAM-1 may regulate CYB-3 during meiotic
      exit but presumably targets other protein(s) to regulate polarity. We also show
      that the pam-1 gene is expressed both maternally and paternally, providing
      additional evidence that sperm-donated gene products have important roles during
      early embryogenesis in C. elegans. The degradation of proteins through ubiquitin
      mediated proteolysis has been previously shown to regulate the cell cycle and AP
      axis formation in the C. elegans zygote. Our analysis of PAM-1 requirements shows
      that a puromycin-sensitive aminopeptidase is also required for proteolytic
      regulation of the oocyte to embryo transition.

PMID- 17021039
TI  - Pax2/5/8 proteins promote cell survival in C. elegans.
AB  - Programmed cell death, or apoptosis, plays an important role during normal
      development, and is disrupted in a range of disease states. Although the key
      molecular events that occur during apoptosis are well characterized, less is
      known about the regulatory inputs that influence whether a cell will live or die.
      Work in mouse and human cells has shown that Pax transcription factors can
      influence cell death and promote cell survival, but the mechanism for their
      activity is not clear. Here, we show that two Pax2/5/8-related genes (egl-38 and
      pax-2) influence both somatic and germline cell death in C. elegans. Using
      genetic and molecular experiments, we show that the Pax proteins act as
      transcriptional regulators of ced-9, the C. elegans bcl-2 gene. These results
      identify a mechanism for Pax2/5/8-mediated regulation of cell death, and
      underscore the importance of transcriptional regulation of core apoptotic pathway
      genes in influencing cell survival.

PMID- 17021040
TI  - Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo.
AB  - The mouse Kcnq1 imprinted domain is located on distal chromosome 7 and contains
      several imprinted genes that are paternally repressed. Repression of these genes
      is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally
      expressed. Maternal repression of Kcnq1ot1 is controlled by DNA methylation
      originating in the oocyte. Some genes in the region are imprinted only in the
      placenta, whereas others are imprinted in both extra-embryonic and embryonic
      lineages. Here, we show that Kcnq1ot1 is paternally expressed in preimplantation
      embryos from the two-cell stage, and that ubiquitously imprinted genes proximal
      to Kcnq1ot1 are already repressed in blastocysts, ES cells and TS cells.
      Repressive histone marks such as H3K27me3 are present on the paternal allele of
      these genes in both ES and TS cells. Placentally imprinted genes that are distal
      to Kcnq1ot1, by contrast, are not imprinted in blastocysts, ES or TS cells. In
      these genes, paternal silencing and differential histone marks arise during
      differentiation of the trophoblast lineage between E4.5 and E7.5. Our findings
      show that the dynamics during preimplantation development of gene inactivation
      and acquisition of repressive histone marks in ubiquitously imprinted genes of
      the Kcnq1 domain are very similar to those of imprinted X inactivation. By
      contrast, genes that are only imprinted in the placenta, while regulated by the
      same non-coding RNA transcript Kcnq1ot1, undergo epigenetic inactivation during
      differentiation of the trophoblast lineage. Our findings establish a model for
      how epigenetic gene silencing by non-coding RNA may depend on distance from the
      non-coding RNA and on lineage and differentiation specific factors.

PMID- 17021041
TI  - Myocardin is a direct transcriptional target of Mef2, Tead and Foxo proteins
      during cardiovascular development.
AB  - Myocardin is a transcriptional co-activator of serum response factor (Srf), which
      is a key regulator of the expression of smooth and cardiac muscle genes.
      Consistent with its role in regulating cardiovascular development, myocardin is
      the earliest known marker specific to both the cardiac and smooth muscle lineages
      during embryogenesis. To understand how the expression of this early
      transcriptional regulator is initiated and maintained, we scanned 90 kb of
      genomic DNA encompassing the myocardin gene for cis-regulatory elements capable
      of directing myocardin transcription in cardiac and smooth muscle lineages in
      vivo. Here, we describe an enhancer that controls cardiovascular expression of
      the mouse myocardin gene during mouse embryogenesis and adulthood. Activity of
      this enhancer in the heart and vascular system requires the combined actions of
      the Mef2 and Foxo transcription factors. In addition, the Tead transcription
      factor is required specifically for enhancer activation in neural-crest-derived
      smooth muscle cells and dorsal aorta. Notably, myocardin also regulates its own
      enhancer, but in contrast to the majority of myocardin target genes, which are
      dependent on Srf, myocardin acts through Mef2 to control its enhancer. These
      findings reveal an Srf-independent mechanism for smooth and cardiac muscle
      restricted transcription and provide insight into the regulatory mechanisms
      responsible for establishing the smooth and cardiac muscle phenotypes during
      development.

PMID- 17021043
TI  - Arabidopsis microRNA167 controls patterns of ARF6 and ARF8 expression, and
      regulates both female and male reproduction.
AB  - In flowering plants, diploid sporophytic tissues in ovules and anthers support
      meiosis and subsequent haploid gametophyte development. These analogous
      reproductive functions suggest that common mechanisms may regulate ovule and
      anther development. Two Arabidopsis Auxin Response Factors, ARF6 and ARF8,
      regulate gynoecium and stamen development in immature flowers. Wild-type pollen
      grew poorly in arf6 arf8 gynoecia, correlating with ARF6 and ARF8 expression in
      style and transmitting tract. ARF6 and ARF8 transcripts are cleavage targets of
      the microRNA miR167, and overexpressing miR167 mimicked arf6 arf8 phenotypes.
      Mutations in the miR167 target sites of ARF6 or ARF8 caused ectopic expression of
      these genes in domains of both ovules and anthers where miR167 was normally
      present. As a result, ovule integuments had arrested growth, and anthers grew
      abnormally and failed to release pollen. Thus, miR167 is essential for correct
      patterning of gene expression, and for fertility of both ovules and anthers. The
      essential patterning function of miR167 contrasts with cases from animals in
      which miRNAs reinforce or maintain transcriptionally established gene expression
      patterns.

PMID- 17021042
TI  - Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy
      related transcription factors.
AB  - Mutations in Notch2, Jagged1 or homologs of the Hairy-related transcriptional
      repressor Hey2 cause congenital malformations involving the non-chamber
      atrioventricular canal (AVC) and inner curvature (IC) regions of the heart, but
      the underlying mechanisms have not been investigated. By manipulating signaling
      directly within the developing chick heart, we demonstrated that Notch2, Hey1 and
      Hey2 initiate a signaling cascade that delimits the non-chamber AVC and IC
      regions. Specifically, misactivation of Notch2 signaling, or misexpression of
      either Hey1 or Hey2, repressed Bmp2. Because Jagged (also known as Serrate in non
      mammalian species) ligands were found to be present in prospective chamber
      myocardium, these data support the model that Notch2 and Hey proteins cause the
      progressive restriction of Bmp2 expression to within the developing AVC and IC,
      where it is essential for differentiation. Misactivation or inhibition of Notch2
      specifically induced or inhibited Hey1, respectively, but these manipulations did
      not affect Hey2, implicating Hey1 as the direct mediator of Notch2. Bmp2 within
      the developing AVC and IC has been shown to induce Tbx2, and we found that Tbx2
      misexpression inhibited the expression of both Hey1 and Hey2. Tbx2, therefore, is
      envisaged to constitute a feedback loop that sharpens the border with the
      developing AVC and IC by delimiting Hey gene expression to within prospective
      chamber regions. Analysis of the loss-of-function phenotype in mouse embryos
      homozygous for targeted disruption of Hey2 revealed an expanded AVC domain of
      Bmp2. Similarly, zebrafish gridlock (Hey2 homolog) mutant embryos showed ectopic
      expression of Bmp4, which normally marks AVC myocardium in this species. Thus,
      Hey pathway regulation of cardiac Bmp appears to be an evolutionarily conserved
      mechanism to delimit AVC and IC fate, and provides a potential mechanistic
      explanation for cardiac malformations caused by mutations in Serrate/Jagged1 and
      Notch signaling components.

PMID- 17021044
TI  - Chromatin assembly factor CAF-1 is required for cellular differentiation during
      plant development.
AB  - Chromatin assembly factor CAF-1 facilitates the formation of nucleosomes on newly
      replicated DNA in vitro. However, the role of CAF-1 in development is poorly
      understood because mutants are not available in most multicellular model
      organisms. Biochemical evidence suggests that FASCIATA1, FASCIATA2 and MSI1 form
      CAF-1 in Arabidopsis thaliana. Because fasciata mutants are viable, CAF-1 is not
      essential for cell division in plants. Arabidopsis CAF-1 mutants have defects in
      shoot apical meristems; in addition, CAF-1 is required to establish seedling
      architecture, leaf size and trichome differentiation. CAF-1 is needed to restrict
      branching of trichomes on rosette leaves. Increased trichome branching in CAF-1
      mutants is not strictly correlated with increased nuclear DNA content. In
      addition, fas2 glabra3 double mutants show an additive genetic interaction,
      demonstrating that CAF-1 acts genetically parallel to the GLABRA3-containing,
      endoreduplication-coupled trichome branching pathway. However, CAF-1 is often
      needed to restrict endoreduplication, because seedlings of most CAF-1 mutants
      have increased ploidy. Notably, in the Landsberg erecta background, loss of CAF-1
      does not affect ploidy, demonstrating that loss of CAF-1 can be compensated in
      some Arabidopsis accessions. These results reveal that the functions of FAS1,
      FAS2 and MSI1 are not restricted to meristems, but are also needed to control
      genome replication at multiple steps of development.

PMID- 17021045
TI  - The roles of cilia in developmental disorders and disease.
AB  - Cilia are highly conserved organelles that have diverse motility and sensory
      functions. Recent discoveries have revealed that cilia also have crucial roles in
      cell signaling pathways and in maintaining cellular homeostasis. As such, defects
      in cilia formation or function have profound effects on the development of body
      pattern and the physiology of multiple organ systems. By categorizing syndromes
      that are due to cilia dysfunction in humans and from studies in vertebrate model
      organisms, molecular pathways that intersect with cilia formation and function
      have come to light. Here, we summarize an emerging view that in order to
      understand some complex developmental pathways and disease etiologies, one must
      consider the molecular functions performed by cilia.

PMID- 17021046
TI  - Odd-skipped genes specify the signaling center that triggers retinogenesis in
      Drosophila.
AB  - Although many of the factors responsible for conferring identity to the eye field
      in Drosophila have been identified, much less is known about how the expression
      of the retinal ;trigger', the signaling molecule Hedgehog, is controlled. Here,
      we show that the co-expression of the conserved odd-skipped family genes at the
      posterior margin of the eye field is required to activate hedgehog expression and
      thereby the onset of retinogenesis. The fly Wnt1 homologue wingless represses the
      odd-skipped genes drm and odd along the anterior margin and, in this manner,
      spatially restricts the extent of retinal differentiation within the eye field.

PMID- 17021047
TI  - Suppression of C/EBPalpha expression in periportal hepatoblasts may stimulate
      biliary cell differentiation through increased Hnf6 and Hnf1b expression.
AB  - The expression of C/EBPalpha, which may govern transcription of mature hepatocyte
      marker genes, was suppressed in periportal hepatoblasts in mouse liver
      development, leading to biliary cell differentiation. This study was undertaken
      to analyze how inactivation of the Cebpa gene affects biliary cell
      differentiation and gene expression of the regulatory genes for that
      differentiation, including Hnf1b and Hnf6. In the knockout mouse liver at
      midgestation stages, pseudoglandular structures were abundantly induced in the
      parenchyma with elevated expression of Hnf6 and Hnf1b mRNAs. The wild-type liver
      parenchyma expressed mRNAs of these transcription factors at low levels, though
      periportal biliary progenitors had strong expression of them. These results
      suggest that expression of Hnf6 and Hnf1b is downstream of C/EBPalpha action in
      fetal liver development, and that the suppression of C/EBPalpha expression in
      periportal hepatoblasts may lead to expression of Hnf6 and Hnf1b mRNAs.
      Immunohistochemical studies with biliary cell markers in knockout livers
      demonstrated that differentiated biliary epithelial cells were confined to around
      the portal veins. The suppression of C/EBPalpha expression may result in
      upregulation of Hnf6 and Hnf1b gene expression, but be insufficient for biliary
      cell differentiation. When liver fragments of Cebpa-knockout fetuses, in which
      hepatoblasts were contained as an endodermal component, were transplanted in the
      testis of Scid (Prkdc) male mice, almost all hepatoblasts gave rise to biliary
      epithelial cells. Wild-type hepatoblasts constructed mature hepatic tissue
      accompanied by biliary cell differentiation. These results also demonstrate that
      the suppression of C/EBPalpha expression may stimulate biliary cell
      differentiation.

PMID- 17021048
TI  - Testosterone and progesterone rapidly attenuate plasma membrane Gbetagamma
      mediated signaling in Xenopus laevis oocytes by signaling through classical
      steroid receptors.
AB  - Many transcription-independent (nongenomic) steroid effects are regulated by G
      proteins. A well-established, biologically relevant example of steroid/G protein
      interplay is steroid-triggered oocyte maturation, or meiotic resumption, in
      Xenopus laevis. Oocyte maturation is proposed to occur through a release of
      inhibition mechanism whereby constitutive signaling by Gbetagamma and other G
      proteins maintains oocytes in meiotic arrest. Steroids (androgens in vivo, and
      androgens and progesterone in vitro) overcome this inhibition to promote meiotic
      resumption. To test this model, we used G protein-regulated inward rectifying
      potassium channels (GIRKs) as markers of Gbetagamma activity. Overexpression of
      GIRKs 1 and 2 in Xenopus oocytes resulted in constitutive potassium influx,
      corroborating the presence of basal Gbetagamma signaling in resting oocytes.
      Testosterone and progesterone rapidly reduced potassium influx, validating that
      steroids attenuate Gbetagamma activity. Interestingly, reduction of classical
      androgen receptor (AR) expression by RNA interference abrogated testosterone's
      effects on GIRK activity at low, but not high, steroid concentrations.
      Accordingly, androgens bound to the Xenopus progesterone receptor (PR) at high
      concentrations, suggesting that, in addition to the AR, the PR might mediate G
      protein signaling when androgens levels are elevated. In contrast, progesterone
      bound with high affinity to both the Xenopus PR and AR, indicating that
      progesterone might signal and promote maturation through both receptors,
      regardless of its concentration. In sum, these studies introduce a novel method
      for detecting nongenomic steroid effects on G proteins in live cells in real
      time, and demonstrate that cross talk may occur between steroids and their
      receptors during Xenopus oocyte maturation.

PMID- 17021049
TI  - Differential utilization of transcription activation subdomains by distinct
      coactivators regulates Pit-1 basal and Ras responsiveness.
AB  - The POU-homeodomain transcription factor Pit-1 governs ontogeny and cell-specific
      gene expression of pituitary lactotropes, somatotropes, and thyrotropes. The
      splice isoform, Pit-1beta, inserts a 26-amino acid (AA) repressor at AA48 in the
      Pit-1 transcription activation domain (TAD). The Pit-1 TAD contains a basal
      regulatory subregion, R1 (AA1-45), and a basal and Ras-responsive region, R2
      (AA46-80). To precisely map these activities, we generated GAL4-Pit-1/Pit
      1betaTAD fusions and, in full-length HA-Pit-1, a series of substitution mutants
      of R2. Analysis in GH4 cells identified an activation domain at AA50-70, followed
      by an overlapping, dual-function, Ras-responsive-inhibitory domain, located from
      AA60-80. In contrast, GAL4-Pit-1betaTAD repressed both basal and Ras-mediated TAD
      activity. To determine the functional interplay between TAD subregions and the
      beta-domain, we inserted the beta-domain every 10 AA across the 80-AA Pit-1 TAD.
      Like wild-type Pit-1beta, each construct retained transcriptional activity in
      HeLa cells and repressed the Ras response in GH4 cells. However, beta-domain
      insertion at AA61 and 71 resulted in greater repression of Ras responsiveness,
      defining a critical R2 TAD spanning AA61-71 of Pit-1. Furthermore, Ras activation
      is augmented by steroid receptor coactivator 1, whereas cAMP response element
      binding protein-binding protein is not a Ras mediator in this system. In summary,
      the Pit-1/Pit-1beta TADs are composed of multiple, modular, and transferable
      subdomains, including a regulatory R1 domain, a basal activation region, a
      selective inhibitory-Ras-responsive segment, and a beta-specific repressor
      domain. These data provide novel insights into the mechanisms by which the Pit-1
      TAD integrates DNA binding, protein partner interactions, and distinct signaling
      pathways to fine-tune Pit-1 activity.

PMID- 17021050
TI  - Functional studies of Akt isoform specificity in skeletal muscle in vivo;
      maintained insulin sensitivity despite reduced insulin receptor substrate-1
      expression.
AB  - The phosphoinositide 3-kinase/Akt pathway is thought to be essential for normal
      insulin action and glucose metabolism in skeletal muscle and has been shown to be
      dysregulated in insulin resistance. However, the specific roles of and signaling
      pathways triggered by Akt isoforms have not been fully assessed in muscle in
      vivo. We overexpressed constitutively active (ca-) Akt-1 or Akt-2 constructs in
      muscle using in vivo electrotransfer and, after 1 wk, assessed the roles of each
      isoform on glucose metabolism and fiber growth. We achieved greater than 2.5-fold
      increases in total Ser473 phosphorylation in muscles expressing ca-Akt-1 and ca
      Akt-2, respectively. Both isoforms caused hypertrophy of muscle fibers,
      consistent with increases in p70S6kinase phosphorylation, and a 60% increase in
      glycogen accumulation, although only Akt-1 increased glycogen synthase kinase
      3beta phosphorylation. Akt-2, but not Akt-1, increased basal glucose uptake (by
      33%, P = 0.004) and incorporation into glycogen and lipids, suggesting a specific
      effect on glucose transport. Consistent with this, short hairpin RNA-mediated
      silencing of Akt-2 caused reductions in glycogen storage and glucose uptake.
      Consistent with Akt-mediated insulin receptor substrate 1 (IRS-1) degradation, we
      observed approximately 30% reductions in IRS-1 protein in muscle overexpressing
      ca-Akt-1 or ca-Akt-2. Despite this, we observed no decrease in insulin-stimulated
      glucose uptake. Furthermore, a 68% reduction in IRS-1 levels induced using short
      hairpin RNAs targeting IRS-1 also did not affect glucose disposal after a glucose
      load. These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose
      metabolism and that moderate reductions in IRS-1 expression do not result in the
      development of insulin resistance in skeletal muscle in vivo.

PMID- 17021051
TI  - An intracellular multi-effector complex mediates somatostatin receptor 1
      activation of phospho-tyrosine phosphatase eta.
AB  - The receptor-like phosphotyrosine phosphatase eta (PTPeta) is an important
      intracellular effector of the cytostatic action of SST. Here we characterize, in
      Chinese hamster ovary-k1 cells, the intracellular pathway that from somatostatin
      receptor 1 (SSTR1), leads to the activation of PTPeta and that involves, in a
      multimeric complex and sequential activation, the tyrosine kinases Janus kinase
      (JAK) 2 and Src, and the cytosolic phosphotyrosine phosphatase SHP-2. We show
      that inhibitors of JAK2 and Src and dominant-negative mutants of SHP-2 and Src
      abolished the SSTR1-mediated PTPeta activation, suggesting that all these
      effectors participate in the activation of PTPeta. In basal conditions, JAK2
      forms a multimeric complex with SHP-2, Src and PTPeta. In response to SST, JAK2
      is activated in a G protein-dependent manner, dissociates from and phosphorylates
      SHP-2, increasing its activity. Subsequently, SHP-2 dissociates from Src,
      dephosphorylates the Src inhibitory tyrosine-529, and causes an autocatalytical
      increase of the phosphorylation of Src tyrosine 418, located inside its kinase
      activation loop. Active Src, in turn, controls the activity of PTPeta, via a
      direct interaction and phosphorylation of the phosphatase. These data for the
      first time depict an intracellular pathway involving a precise sequence of
      interactions and cross-activation among tyrosine phosphatases and kinases acting
      upstream of PTPeta. In particular the sequential activation of JAK2, SHP-2, and
      Src conveys the molecular signaling from SSTR1 to the activation of this
      phosphatase that is responsible for the final biological effects of SST.

PMID- 17021052
TI  - Hypermetabolism of fat in V1a vasopressin receptor knockout mice.
AB  - [Arg8]Vasopressin (AVP) has an antilipolytic action on adipocytes, but little is
      known about the mechanisms involved. Here, we examined the involvement of the V1a
      receptor in the antilipolytic effect of AVP using V1a receptor-deficient (V1aR-/
      ) mice. The levels of blood glycerol were increased in V1aR-/- mice. The levels
      of ketone bodies, such as acetoacetic acid and 3-hydroxybutyric acid, the
      products of the lipid metabolism, were increased in V1aR-/- mice under a fasting
      condition. Triacylglyceride and free fatty acid levels in blood were decreased in
      V1aR-/- mice. Furthermore, measurements with tandem mass spectrometry determined
      that carnitine and acylcarnitines in serum, the products of beta-oxidation, were
      increased in V1aR-/- mice. Most acylcarnitines were increased in V1aR-/- mice,
      especially in the case of 2-carbon (C2), C10:1, C10, C14:1, C16, C18:1, and
      hydroxy-18:1-carbon (OH-C18:1)-acylcarnitines under feeding rather than under
      fasting conditions. The analysis of tissue C2-acylcarnitine level showed that
      beta-oxidation was promoted in muscle under the feeding condition and in liver
      under the fasting condition. An in vitro assay using brown adipocytes showed that
      the cells of V1aR-/- mice were more sensitive to isoproterenol for lipolysis.
      These results suggest that the lipid metabolism is enhanced in V1aR-/- mice. The
      cAMP level was enhanced in V1aR-/- mice in response to isoproterenol. The
      phosphorylation of Akt by insulin stimulation was reduced in V1aR-/- mice. These
      results suggest that insulin signaling is suppressed in V1aR-/- mice. In
      addition, the total bile acid, taurine, and cholesterol levels in blood were
      increased, and an enlargement of the cholecyst was observed in V1aR-/- mice.
      These results indicated that the production of bile acid was enhanced by the
      increased level of cholesterol and taurine. Therefore, these results indicated
      that AVP could modulate the lipid metabolism by the antilipolytic action and the
      synthesis of bile acid via the V1a receptor.

PMID- 17021053
TI  - Focal subnuclear distribution of progesterone receptor is ligand dependent and
      associated with transcriptional activity.
AB  - The progesterone receptor (PR) is a critical mediator of progesterone action in
      the female reproductive system. Expressed in the human as two proteins, PRA and
      PRB, the receptor is a ligand-activated nuclear transcription factor that
      regulates transcription by interaction with protein cofactors and binding to
      specific response elements in target genes. We previously reported that PR was
      located in discrete subnuclear foci in human endometrium. In this study, we
      investigated the role of ligand in the formation of PR foci and their association
      with transcriptional activity. PR foci were detected in mouse uterus and normal
      human breast tissues and were more abundant when circulating progesterone was
      high. In human malignant tissues, PR foci were aberrant: foci were larger in
      endometrial cancers than in normal endometrium, and in breast cancers hormone
      dependence was decreased. Chromatin disruption also increased foci size and
      decreased ligand dependence, suggesting that altered nuclear architecture may
      contribute to the aberrant PR foci observed in endometrial and breast cancers. In
      breast cancer cells, movement of PR into foci required exposure to ligand and was
      blocked by transcriptional inhibitors and by prolonged inhibition of proteasomal
      degradation. Foci contained PR dimers, and fluorescence resonance energy transfer
      demonstrated that PR foci contained the highest concentration of receptor dimers
      in the nucleus. PR in foci colocalized with transcription factors and nascent RNA
      transcripts only in the presence of ligand, and inhibition of coactivator
      recruitment inhibited PR foci formation. The demonstration that focal
      distribution of PR within the nucleus is associated with transcription suggests a
      link between the subnuclear distribution of PR and its transcriptional activity
      that is likely to be important for normal cellular function of PR.

PMID- 17021054
TI  - Monitoring of stool microbiota in subjects with diarrhea indicates distortions in
      composition.
AB  - We utilized denaturing gradient gel electrophoresis profiling to survey stool
      microbiota in 175 persons with diarrhea and 113 asymptomatic persons in a
      diarrhea surveillance study. Compared with healthy controls, the microbiota
      profiles in diarrhea cases more frequently exhibited decreased diversity and
      strong bands indicating the overgrowth of selected bacteria or bacterial groups.

PMID- 17021056
TI  - Combined hepatitis C virus (HCV) antigen-antibody detection assay does not
      improve diagnosis for seronegative individuals with occult HCV infection.
AB  - A combined hepatitis C virus (HCV) antigen-antibody assay was evaluated for 115
      seronegative individuals with occult HCV infection. The assay was reactive in one
      patient and negative to weakly reactive in three others (all four gave
      indeterminate results by supplemental assay) but failed to detect HCV in the
      remaining patients. Despite increased sensitivity the combined assay does not
      improve serodiagnosis of occult HCV infection.

PMID- 17021055
TI  - Relationship between prevalent oral and cervical human papillomavirus infections
      in human immunodeficiency virus-positive and -negative women.
AB  - Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and
      cervical cancers, yet little is known about the interrelationship between oral
      and cervical HPV infections. Therefore, we compared the prevalences and type
      distributions of oral and cervical HPV infections and evaluated infection
      concordance in a cross-sectional study within the Women's Interagency HIV Study
      cohort. Oral rinse and cervical-vaginal lavage samples were concurrently
      collected from a convenience sample of 172 human immunodeficiency virus (HIV)
      positive and 86 HIV-negative women. HPV genomic DNA was detected by PGMY09/11 L1
      consensus primer PCR and type specified by reverse line blot hybridization for 37
      HPV types and beta-globin. Only 26 of the 35 HPV types found to infect the cervix
      were also found within the oral cavity, and the type distribution for oral HPV
      infections appeared distinct from that for cervical infections (P<0.001). Oral
      HPV infections were less common than cervical infections for both HIV-positive
      (25.2% versus 76.9%, P<0.001) and HIV-negative (9.0% versus 44.9%, P<0.001)
      women. Oral HPV infections were more common among women with a cervical HPV
      infection than those without a cervical HPV infection (25.5% versus 7.9%,
      P=0.002). The majority of women (207; 93.7%) did not have simultaneous oral and
      cervical infections by the same HPV type; however, the number of women who did
      (14; 6.3%) was significantly greater than would be expected by chance (P=0.0002).
      Therefore, the oral and cervical reservoirs for HPV infection are likely not
      entirely independent of one another.

PMID- 17021057
TI  - Determination of MICs of aminocandin for Candida spp. and filamentous fungi.
AB  - Candida and Aspergillus spp., as well as other filamentous molds, have
      increasingly been reported as the causes of severe invasive fungal infections. We
      evaluated the new echinocandin aminocandin (AMN) for its antifungal activities
      against a range of fungal pathogens by determination of the MICs for the
      organisms. The MICs of the comparator drugs amphotericin B, caspofungin,
      micafungin, and voriconazole were also determined. The MICs of AMN for 25 strains
      each of non-Candida albicans Candida spp. (including Candida parapsilosis,
      Candida krusei, Candida guilliermondii, and Candida tropicalis), Aspergillus
      fumigatus, Scedosporium spp., Fusarium spp., and zygomycetes (including Absidia,
      Mucor, and Rhizopus spp.) were determined by using the Clinical and Laboratory
      Standards Institute M27-A2 and M38-A methodologies for yeasts and filamentous
      molds, respectively. The MIC ranges of AMN for all yeasts were similar (0.03 to
      4.0 microg/ml), while the MIC ranges of AMN for filamentous fungi were species
      specific. AMN demonstrated potent antifungal activity against A. fumigatus,
      limited activity against Scedosporium spp., and no activity against zygomycetes
      or Fusarium spp. Our data showed that AMN demonstrated potent antifungal
      activities against all of the yeasts and Aspergillus isolates tested, suggesting
      that AMN could be an important addition to our arsenal of antifungals for the
      treatment of invasive fungal disease.

PMID- 17021058
TI  - Development of a serotype-specific DNA microarray for identification of some
      Shigella and pathogenic Escherichia coli strains.
AB  - Shigella and pathogenic Escherichia coli are major causes of human infectious
      diseases and are responsible for millions of cases of diarrhea worldwide every
      year. A convenient and rapid method to identify highly pathogenic serotypes of
      Shigella and E. coli is needed for large-scale epidemiologic study, timely
      clinical diagnosis, and reliable quarantine of the pathogens. In this study, a
      DNA microarray targeting O-serotype-specific genes was developed to detect 15
      serotypes of Shigella and E. coli, including Shigella sonnei; Shigella flexneri
      type 2a; Shigella boydii types 7, 9, 13, 16, and 18; Shigella dysenteriae types
      4, 8, and 10; and E. coli O55, O111, O114, O128, and O157. The microarray was
      tested against 186 representative strains of all Shigella and E. coli O
      serotypes, 38 clinical isolates, and 9 strains of other bacterial species that
      are commonly present in stool samples and was shown to be specific and
      reproducible. The detection sensitivity was 50 ng genomic DNA or 10(4) CFU per ml
      in mock stool specimens. This is the first report of a microarray for serotyping
      Shigella and pathogenic E. coli. The method has a number of advantages over
      traditional bacterial culture and antiserum agglutination methods and is
      promising for applications in basic microbiological research, clinical diagnosis,
      food safety, and epidemiological surveillance.

PMID- 17021059
TI  - Establishing clonal relationships between VIM-1-like metallo-beta-lactamase
      producing Pseudomonas aeruginosa strains from four European countries by
      multilocus sequence typing.
AB  - Ten multidrug-resistant Pseudomonas aeruginosa strains producing VIM-1-like
      acquired metallo-beta-lactamases (MBLs), isolated from four European countries
      (Greece, Hungary, Italy, and Sweden), were analyzed for genetic relatedness by
      several methodologies, including fliC sequence analysis, macrorestriction
      profiling of genomic DNA by pulsed-field gel electrophoresis (PFGE), random
      amplification of polymorphic DNA (RAPD), and multilocus sequence typing (MLST).
      The four approaches yielded consistent results overall but showed different
      resolution powers in establishing relatedness between isolates
      (PFGE>RAPD>MLST>fliC typing) and could usefully complement each other to address
      issues in the molecular epidemiology of P. aeruginosa strains producing acquired
      MBLs. In particular, the recently developed MLST approach was useful in revealing
      clonal relatedness between isolates when this was not readily apparent using RAPD
      and PFGE, and it suggested a common ancestry for some of the VIM-1-like MBL
      positive P. aeruginosa strains currently spreading in Europe. The MBL producers
      belonged in three clonal complexes/burst groups (BGs). Of these, one corresponded
      to the previously described BG4 and included serotype O12 strains from Hungary
      and Sweden, while the other two were novel and included serotype O11 or
      nonserotypable strains from Greece, Sweden, and/or Italy. Comparison of the
      integrons carrying blaVIM-1-like cassettes of various isolates revealed a
      remarkable structural heterogeneity, suggesting the possibility that multiple
      independent events of acquisition of different blaVIM-containing integrons had
      occurred in members of the same clonal lineage, although a contribution of
      integrase-mediated cassette shuffling or other recombination mechanisms during
      the evolution of similar strains could also have played a role in determining
      this variability.

PMID- 17021060
TI  - Assessing the genetic diversity of the aldolase genes of Plasmodium falciparum
      and Plasmodium vivax and its potential effect on performance of aldolase
      detecting rapid diagnostic tests.
AB  - Malaria-specific rapid diagnostic tests (RDTs) targeting aldolase show highly
      variable sensitivities. We assessed diversity in Plasmodium falciparum and P.
      vivax aldolases by sequencing the coding genes from parasites of various origins.
      The results show that aldolases are highly conserved, indicating that antigenic
      diversity is not a cause of variable RDT sensitivity.

PMID- 17021061
TI  - Laribacter hongkongensis isolated from a patient with community-acquired
      gastroenteritis in Hangzhou City.
AB  - We describe the isolation of Laribacter hongkongensis in Hangzhou City, People's
      Republic of China. One strain of bacterium, named LHHZ242, had many of the same
      phenotypic and genotypic characteristics as Laribacter hongkongensis described in
      previous publications. This discovery proves that Laribacter hongkongensis is
      also associated with community-acquired gastroenteritis outside Hong Kong.

PMID- 17021062
TI  - Rapid screening of topoisomerase gene mutations by a novel melting curve analysis
      method for early warning of fluoroquinolone-resistant Streptococcus pneumoniae
      emergence.
AB  - We developed a real-time PCR assay combined with melting curve analysis for
      rapidly genotyping quinolone resistance-determining regions (QRDR) of
      topoisomerase genes in Streptococcus pneumoniae. This assay was not only accurate
      for the screening of fluoroquinolone (FQ) resistance but also relevant as an
      early warning system for detecting preexisting single QRDR mutations.

PMID- 17021063
TI  - Blood culture contamination in Tanzania, Malawi, and the United States: a
      microbiological tale of three cities.
AB  - We conducted retrospective, comparative analyses of contamination rates for
      cultures of blood obtained in the emergency rooms of Muhimbili National Hospital
      (MNH) in Dar es Salaam, Tanzania; Lilongwe Central Hospital (LCH) in central
      Malawi; and the Duke University Medical Center (DUMC) in the United States. None
      of the emergency room patients had indwelling intravascular devices at the time
      that the blood samples for cultures were obtained. In addition, we reviewed the
      contamination rates for a cohort of patients already hospitalized in the DUMC
      inpatient medical service, most of whom had indwelling intravascular devices. The
      bloodstream infection rates among the patients at MNH (n=513) and LCH (n=486)
      were similar (approximately 28%); the contamination rates at the two hospitals
      were 1.3% (7/513) and 0.8% (4/486), respectively. Of 54 microorganisms isolated
      from cultures of blood collected in the DUMC emergency room, 26 (48%) were
      identified as skin contaminants. Cultures of blood collected in the DUMC
      emergency room were significantly more likely to yield growth of contaminants
      than the cultures of blood collected in the emergency rooms at MNH and LCH
      combined (26/332 versus 11/1,003; P<0.0001) or collected in the DUMC inpatient
      medical service (26/332 versus 7/283; P<0.01). For the MNH and LCH blood
      cultures, lower contamination rates were observed when skin was disinfected with
      isopropyl alcohol plus tincture of iodine rather than isopropyl alcohol plus
      povidone-iodine. In conclusion, blood culture contamination was minimized in sub
      Saharan African hospitals with substantially limited resources through scrupulous
      attention to aseptic skin cleansing and improved venipuncture techniques.
      Application of these principles when blood samples for culture are obtained in
      U.S. hospital emergency rooms should help mitigate blood culture contamination
      rates and the unnecessary microbiology workup of skin contaminants.

PMID- 17021064
TI  - Longitudinal study of the molecular epidemiology of methicillin-resistant
      Staphylococcus aureus at a university hospital.
AB  - Surveillance for methicillin-resistant Staphylococcus aureus (MRSA) at the
      University Hospital of Heidelberg revealed an increase in the numbers of newly
      detected MRSA isolates in recent years. We conducted a study to assess the
      dynamics of the changes in the MRSA population. Pulsed-field gel electrophoresis
      (PFGE) typing of MRSA isolates from all patients at the University Hospital of
      Heidelberg collected between 1993 and 2004 was performed. The microbiology
      database contained 1,807 entries for newly detected MRSA isolates from 1,301
      patients. A total of 1,252 isolates were available for PFGE typing. The isolates
      could be classified into 109 different PFGE types. Most PFGE types (n=70) were
      detected less than five times and showed no evidence of transmission (sporadic
      strains). They accounted for 8.7% of all isolates, with few variations in
      frequency over the time. Thirty-seven PFGE types were clustered by time of
      detection, and transmission of the strains was likely (local epidemic strains). A
      total of 37.3% of the isolates belonged to this group of strains. The remaining
      54.0% of the isolates belonged to only two further PFGE types (endemic strains).
      One endemic strain accounted for 5.0% of all isolates in 1994 and 68.2% in 2004.
      A second endemic strain was detected in 1.1% of all isolates in 1998 but in 12.4%
      in 2004. Statistical analysis of the associations between the kind of strain
      (sporadic, local epidemic, or endemic) and the patients' characteristics revealed
      a significant association for age and mode of acquisition. The remarkable
      increase in the rate of MRSA detection at the University Hospital of Heidelberg
      is mainly due to the dissemination of two different strains. Infection control
      measures seemed sufficient to prevent further transmission of some but not all of
      the strains.

PMID- 17021065
TI  - Comparison of mannitol salt agar and blood agar plates for identification and
      susceptibility testing of Staphylococcus aureus in specimens from cystic fibrosis
      patients.
AB  - Antimicrobial susceptibilities of Staphylococcus aureus strains can be determined
      accurately by using isolates from mannitol salt agar, and yellow isolates on
      mannitol salt agar at quantities of >1+ can be reported as S. aureus. These
      methods decrease the time to identification/antimicrobial susceptibility testing
      of S. aureus and decrease costs through eliminating additional testing.

PMID- 17021066
TI  - Two patients coinfected with Mycobacterium leprae and human immunodeficiency
      virus type 1 and naive for antiretroviral therapy who exhibited type 1 leprosy
      reactions mimicking the immune reconstitution inflammatory syndrome.
AB  - Two case reports of patients with human immunodeficiency virus type 1 (HIV-1)
      infection who developed leprosy are presented. Both developed type 1 leprosy
      reactions in the absence of antiretroviral therapy. Reactions have been described
      for a number of HIV-1- and Mycobacterium leprae-coinfected patients and have been
      considered to be part of an immune reconstitution inflammatory syndrome (IRIS)
      since the reactions were usually linked to the administration of highly active
      antiretroviral therapy. The reports of our two patients suggest that the type 1
      reactions in patients with leprosy and HIV may not always be an IRIS
      manifestation but may be akin to the classical reactional state described for the
      natural course of leprosy infection, which occurs in leprosy patients due to the
      fluctuations of the antimycobacterial immune response, whether they are
      coinfected with HIV or not.

PMID- 17021067
TI  - Simultaneous quantification and genotyping of hepatitis B virus for genotypes A
      to G by real-time PCR and two-step melting curve analysis.
AB  - Both the viral titer and the genotype significantly determine clinical outcomes
      and responses to antiviral treatment in chronic hepatitis B virus (HBV)
      infection. A method was developed for large-scale A-to-G genotyping with
      simultaneous viral quantification. The assay was run on a LightCycler instrument
      using hybridization probes. The genotype was determined from the melting points
      of the probes in a two-step manner. Set 1 amplicons differentiated genotypes B,
      E, and F from A, C, D, and G and simultaneously quantified viremia by real-time
      PCR. Melting curve analysis using the set 2-1 amplicon or the set 2-2 amplicon
      reaction mixture was then used to differentiate these genotype groups into single
      genotypes. HBV DNA quantification was consistent with that of the Amplicor assay
      and linear in a range from 10(2) to 10(13) copies/ml. By comparison with the
      restriction fragment length polymorphism method, 92.3% of 441 samples were
      accurately genotyped by the current assay. The method should be useful for
      genotyping and quantification of HBV DNA in areas where all genotypes exist.

PMID- 17021068
TI  - Candida pseudorugosa sp. nov., a novel yeast species from sputum.
AB  - Two yeast strains, strains XH 1026 and XH 1164, isolated from the sputum of an
      intensive care unit patient with acute pneumonia, were originally identified as
      Candida albicans and C. tropicalis, respectively. Sequence analysis of the 26S
      rRNA gene D1/D2 domain and the internal transcribed spacer (ITS) region indicated
      that the two strains represent a novel yeast species closely related to C.
      rogusa. The name Candida pseudorugosa sp. nov. is therefore proposed (type
      strain, AS 2.3107 [CBS 10433]). The new species is able to grow at 42 degrees C
      and is resistant or insusceptible to amphotericin B (MIC, 2 microg/ml),
      caspofungin (MIC, 64 microg/ml), itraconazole (MIC, 1 microg/ml), and nystatin
      (MIC, 16 microg/ml); dose-dependent susceptible to fluconazole (MIC, 16
      microg/ml); and susceptible to flucytosine (MIC, 0.125 microg/ml) and
      voriconazole (MIC, 0.125 to 0.25 microg/ml). The code for C. pseudorugosa sp.
      nov. provided by the API 20C AUX system is identical to that for C. rugosa. The
      colonies of the new species on CHROMagar Candida appear blue-green, similar to
      those of C. albicans. In addition to the molecular method based on D1/D2 domain
      or ITS region sequencing, use of the combination of the API system and CHROMagar
      Candida is helpful for the correct identification of C. pseudorugosa sp. nov.

PMID- 17021069
TI  - Home testing to detect human immunodeficiency virus: boon or bane?

PMID- 17021070
TI  - Genetic background and antibiotic resistance of Staphylococcus aureus strains
      isolated in the Republic of Georgia.
AB  - The genetic composition and antibiotic sensitivities of 50 clinical isolates of
      Staphylococcus aureus obtained from various clinics in the Republic of Georgia
      were characterized. S. aureus strains ATCC 700699 and ATCC 29737 were included as
      reference standards in all analyses. All 52 strains had identical 16S rRNA
      profiles. In contrast, pulsed-field gel electrophoresis (PFGE) identified 20
      distinct PFGE types among the 52 strains examined, which indicates that PFGE is
      more discriminating than is 16S rRNA sequence analysis for differentiating S.
      aureus strains. The results of our PFGE typing also suggest that multiple genetic
      subpopulations (related at the ca. 85% similarity level, based on their SmaI PFGE
      patterns) exist among the Georgian S. aureus strains. Twenty-two of the 50
      Georgian strains were methicillin resistant and PCR positive for mecA, and 5
      strains were methicillin sensitive even though they possessed mecA. None of the
      strains were vancomycin resistant or contained vanA. The nucleotide sequences of
      mecA fragments obtained from all mecA-containing strains were identical. Our data
      indicate that the population of S. aureus strains in Georgia is fairly
      homogeneous and that the prevalence of methicillin-resistant, mecA-positive
      strains is relatively high in that country.

PMID- 17021071
TI  - Common virulence factors and genetic relationships between O18:K1:H7 Escherichia
      coli isolates of human and avian origin.
AB  - Extraintestinal pathogenic (ExPEC) Escherichia coli strains of serotype O18:K1:H7
      are mainly responsible for neonatal meningitis and sepsis in humans and belong to
      a limited number of closely related clones. The same serotype is also frequently
      isolated from the extraintestinal lesions of colibacillosis in poultry, but it is
      not well known to what extent human and avian strains of this particular serotype
      are related. Twenty-two ExPEC isolates of human origin and 33 isolates of avian
      origin were compared on the basis of their virulence determinants, lethality for
      chicks, pulsed-field gel electrophoresis (PFGE) patterns, and classification in
      the main phylogenetic groups. Both avian and human isolates were lethal for
      chicks and harbored similar virulence genotypes. A major virulence pattern,
      identified in 75% of the isolates, was characterized by the presence of F1
      variant fimbriae; S fimbriae; IbeA; the aerobactin system; and genomic fragments
      A9, A12, D1, D7, D10, and D11 and by the absence of P fimbriae, F1C fimbriae, Afa
      adhesin, and CNF1. All but one of the avian and human isolates also belonged to
      major phylogenetic group B2. However, various subclonal populations could be
      distinguished by PFGE in relation to animal species and geographical origin.
      These results demonstrate that very closely related clones can be recovered from
      extraintestinal infections in humans and chickens and suggest that avian
      pathogenic E. coli isolates of serotype O18:K1:H7 are potential human pathogens.

PMID- 17021072
TI  - Mycobacterium barrassiae sp. nov., a Mycobacterium moriokaense group species
      associated with chronic pneumonia.
AB  - Three identical isolates of new rapidly growing mycobacteria (RGM) were recovered
      from the bronchial aspirate and sputum from a 49-year-old woman presenting with
      lung lesions. The case met the American Thoracic Society criteria for the
      diagnosis of nontuberculous mycobacterial infection. The three isolates grew in 3
      days at 24 to 42 degrees C. The 16S rRNA gene sequence analysis indicated that
      the sequences of the isolates were identical and shared 99.7% and 98.1%
      similarities with those of Mycobacterium moriokaense and Mycobacterium gadium,
      respectively. Partial 723-bp rpoB sequence analyses indicated that the sequences
      of the isolates shared 95.8% and 92.3% similarities with those of M. moriokaense
      and M. gadium, respectively. Polyphasic identification (including biochemical
      tests; antimicrobial susceptibility profiling; and hsp65, recA, and sodA gene
      sequence analyses, as well as G+C content determination and cell wall fatty acid
      composition analysis) supported the evidence that these isolates were
      representative of a new species. Phylogenetic analyses confirmed the close
      relationships of the isolates with M. moriokaense and the defined M. moriokaense
      group. These isolates were susceptible to the antimicrobials currently
      recommended for the treatment of RGM infections. These isolates differed from M.
      moriokaense by their susceptibility to vancomycin. We propose the name
      Mycobacterium barrassiae sp. nov. for this new species. The type strain is N7T
      (CIP 108545T and CCUG 50398T).

PMID- 17021074
TI  - Evaluation of the BD Phoenix automated microbiology system for identification and
      antimicrobial susceptibility testing of Enterobacteriaceae.
AB  - We evaluated the accuracy of the BD Phoenix system for the identification (ID)
      and antimicrobial susceptibility testing (AST) of 251 isolates of the family
      Enterobacteriaceae representing 31 species. Organisms were inoculated onto the
      Phoenix panel according to the manufacturer's instructions. The results from
      conventional biochemical tests were used for the reference method for ID. Agar
      dilution, performed according to the CLSI guidelines, was the reference AST
      method. Essential and categorical agreements were determined. The overall levels
      of agreement for the genus- and species-level identifications were 95.6% and
      94.4%, respectively. Fourteen isolates were incorrectly identified by the Phoenix
      system; 10 of these were incorrectly identified to the species level. Three of
      these were Enterobacter (Pantoea) species and four of these were Shigella spp.
      misidentified as Escherichia coli. For AST results, the essential and categorical
      agreements were 98.7% and 97.9%, respectively. The very major error, major error,
      and minor error rates were 0.38%, 0.33%, and 1.8%, respectively. Six isolates
      (three E. coli isolates and three Klebsiella isolates) were extended-spectrum
      beta-lactamase producers. All six were flagged by the Phoenix system expert
      rules. The Phoenix system compares favorably to traditional methods for ID and
      AST of Enterobacteriaceae.

PMID- 17021073
TI  - Molecular epidemiology of rotavirus diarrhea among children and adults in Nepal:
      detection of G12 strains with P[6] or P[8] and a G11P[25] strain.
AB  - In anticipation of a rotavirus vaccine in Nepal, this study was undertaken to
      determine the distribution of the G and P serotypes and electropherotypes of
      rotaviruses in order to examine if there is any emerging serotype or unusual
      strain circulating in children and adults in Nepal. Of 1,315 diarrheal stool
      specimens, rotavirus was detected by an enzyme-linked immunosorbent assay in 116
      (17%) of 666 patients less than 5 years of age, in 18 (7%) of 260 patients 5 to
      14 years of age, and in 19 (5%) of 358 patients 15 years of age and older.
      Approximately 75% of rotavirus diarrhea occurred in children less than 5 years of
      age. Approximately 70% of rotaviruses found in each of the three age groups
      belonged to serotype G1P[8]. Interestingly, there were 29 (20%) G12 rotaviruses
      carrying either P[8] or P[6] and one (0.7%) G11 rotavirus carrying an unusual
      P[25] genotype. RNA polyacrylamide gel electrophoresis discriminated 19 strains
      (electropherotypes), among which there were three codominant strains carrying
      G1P[8] and long RNA patterns. Five electropherotypes were discriminated among G12
      rotaviruses, all of which had long RNA patterns. The fact that 20% of rotaviruses
      were G12 strains carrying either P[8] or P[6] and had multiple electropherotypes
      suggest that G12 strains are not more rare strains but that they pose an emerging
      challenge to current and future vaccines. The presence of multiple strains as
      defined by electropherotypes suggests the richness of the rotavirus gene pool in
      Nepal, where unusual strains may continue to emerge.

PMID- 17021075
TI  - Species-specific identification of Leptospiraceae by 16S rRNA gene sequencing.
AB  - The genus Leptospira is classified into 13 named species and 4 genomospecies
      based upon DNA-DNA reassociation studies. Phenotypic tests are unable to
      distinguish between species of Leptospira, and there is a need for a simplified
      molecular approach to the identification of leptospires. 16S rRNA gene sequences
      are potentially useful for species identification of Leptospira, but there are a
      large number of sequences of various lengths and quality in the public databases.
      16S rRNA gene sequences of near full length and bidirectional high redundancy
      were determined for all type strains of the species of the Leptospiraceae. Three
      clades were identified within the genus Leptospira, composed of pathogenic
      species, nonpathogenic species, and another clade of undetermined pathogenicity
      with intermediate 16S rRNA gene sequence relatedness. All type strains could be
      identified by 16S rRNA gene sequences, but within both pathogenic and
      nonpathogenic clades as few as two or three base pairs separated some species.
      Sequences within the nonpathogenic clade were more similar, and in most cases <
      or =10 bp distinguished these species. These sequences provide a reference
      standard for identification of Leptospira species and confirm previously
      established relationships within the genus. 16S rRNA gene sequencing is a
      powerful method for identification in the clinical laboratory and offers a
      simplified approach to the identification of Leptospira species.

PMID- 17021076
TI  - Molecular identification of black-grain mycetoma agents.
AB  - Black-grain mycetomas are subcutaneous devastating chronic infections due to
      several dematiaceous fungi. They are diagnosed mostly in tropical countries.
      Identification of these fungi with standard mycological procedures is difficult
      because of their poor or delayed sporulation. The aim of this study was thus to
      assess the accuracy of molecular identification of these fungi. A total of 54
      strains, mostly of clinical origin, were used, including 15 Madurella
      mycetomatis, 6 Madurella grisea, 12 Leptosphaeria senegalensis, 4 Leptosphaeria
      tompkinsii, 6 Pyrenochaeta spp., 4 Curvularia lunata, and 7 Exophiala jeanselmei
      strains. The internal transcribed spacer 1 (ITS1)-5.8S-ITS2 DNA region was
      amplified by using universal fungal primers and sequenced. Both intra- and
      interspecies sequence similarities were assessed. Madurella mycetomatis appeared
      to be a homogeneous species. More intraspecies variations were found for C.
      lunata and E. jeanselmei, leading, in some instances, to changes in the initial
      identification. L. senegalensis and L. tompkinsii showed intraspecies
      similarities of >99%, but similarity between the two species was <88%.
      Intergenera and interspecies variations were important, with sequence homologies
      of <81% between genera. In contrast, Pyrenochaeta romeroi and M. grisea appeared
      to be heterogeneous, with intraspecies similarities of 40 to 100% and 53 to 100%,
      respectively, which suggest either erroneous identification or the need for
      taxonomic revision. Epidemiological and therapeutic studies could benefit from a
      precise identification of the fungi responsible for black-grain mycetoma based
      not only on phenotypical characteristics but also on ITS sequencing.

PMID- 17021077
TI  - Vancomycin-tolerant Streptococcus pneumoniae in Korea.
AB  - A nationwide surveillance study was undertaken to monitor antimicrobial
      resistance among clinical isolates of Streptococcus pneumoniae in Korea, with a
      special focus on vancomycin tolerance. For the 6-month period from March to
      August 2002, clinical isolates of S. pneumoniae were collected from 11 university
      hospitals and 1 reference laboratory. One-hundred eighty-eight isolates were
      measured for lysis rates after exposure to vancomycin for 4 h. Two vancomycin
      tolerant S. pneumoniae (VTSP) strains, S3 and H8, were isolated from sputum
      cultures of two patients, who had stayed in intensive-care units of different
      hospitals with long-term antibiotic therapy and were not treated for pneumococcal
      pneumonia. The penicillin, cefotaxime, and vancomycin MICs for S3 were 8
      microg/ml, >16 microg/ml, and 0.5 microg/ml, and those for H8 were 2 microg/ml, 2
      microg/ml, and 0.5 microg/ml, respectively. While S3 belonged to serotype 23F and
      was autolysin defective, H8 belonged to serotype 13F and had intact autolysin.
      These strains were not clonally related as determined by pulsed-field gel
      electrophoresis of chromosomal DNA. In agreement with previous reports, both
      isolates showed pairing of TIGR4 vex2 with R6 pep27 and had two identical amino
      acid substitutions, Q441K in vncS and N25D in vex2. These findings indicate that
      two VTSP strains have emerged independently in Korea, suggesting a prevalence
      rate of 1.1%. The emergence of VTSP would be a serious threat in Korea, where
      there are significant rates of penicillin resistance in S. pneumoniae. Monitoring
      of the prevalence of VTSP and further investigation of the clinical relevance of
      VTSP are warranted.

PMID- 17021078
TI  - Comparison of phenotypic with genotypic procedures for confirmation of coagulase
      negative Staphylococcus catheter-related bloodstream infections.
AB  - We sought here to review the present definition of catheter-related bloodstream
      infections (CR-BSI) due to coagulase-negative staphylococci (CNS) by comparing
      the routine phenotypic methods with a genotypic procedure that considers
      different morphotypes. Our phenotypic characterization of CNS isolates included
      routine identification with biotype and antibiotype. The genotypic diagnosis was
      based on longer incubation periods with the consideration of all morphotypes and
      molecular typing by pulsed-field gel electrophoresis techniques. We prospectively
      selected 61 episodes of suspected CR-BSI by CNS occurring during 1 year, based on
      the presence of a compatible clinical setting and the isolation of one or more
      CNS from blood and catheter tip. Of these episodes, 47 (77%) were identified as
      true episodes of CR-BSI based on the presence of microorganisms of the same
      genotype in the blood and on the catheter tip. The sensitivity, specificity,
      positive predictive, negative predictive, accuracy, positive likelihood ratio,
      and negative likelihood ratio values obtained by different phenotypic
      microbiological approaches to establish the diagnosis of CR-BSI were as follows:
      identity at species level (78.7%, 85.7%, 94.9%, 54.5%, 80.3%, 5.51, and 0.25,
      respectively); identity of species and biotype (59.6%, 92.9%, 96.6%, 40.6%,
      67.2%, 8.34, and 0.44, respectively); identity of species and antibiotype (61.7%,
      92.9%, 96.7%, 41.9%, 68.8%, 8.64, and 0.41, respectively); and identity of
      species, biotype, and antibiotype (48.9%, 92.9%, 95.8%, 35.1%, 59%, 6.85, and
      0.55, respectively). Our study demonstrates the inaccuracy of the diagnosis of
      CNS CR-BSI when the current definition based on conventional routine
      microbiological practice is followed. A new definition of CNS CR-BSI is
      necessary, at least as an epidemiological and research tool.

PMID- 17021079
TI  - Global surveillance of in vitro activity of micafungin against Candida: a
      comparison with caspofungin by CLSI-recommended methods.
AB  - Micafungin is an echinocandin antifungal agent that has recently been approved
      for the prevention of invasive fungal infection and the treatment of esophageal
      candidiasis. Prospective sentinel surveillance for the emergence of in vitro
      resistance to micafungin among invasive Candida sp. isolates is indicated. We
      determined the in vitro activity of micafungin against 2,656 invasive
      (bloodstream or sterile site) unique patient isolates of Candida spp. collected
      from 60 medical centers worldwide in 2004 and 2005. We performed antifungal
      susceptibility testing according to the Clinical and Laboratory Standards
      Institute (CLSI) M27-A2 method and used a 24-hour prominent inhibition endpoint
      for determination of the MIC. Caspofungin was tested in parallel against all
      isolates. Of 2,656 invasive Candida sp. isolates, species distribution was 55.6%
      Candida albicans, 14.4% Candida parapsilosis, 13.4% Candida glabrata, 10.1%
      Candida tropicalis, 2.4% Candida krusei, 1.7% Candida guilliermondii, 0.9%
      Candida lusitaniae, 0.6% Candida kefyr, and 0.9% other Candida species. Overall,
      micafungin was very active against Candida (MIC50/MIC at which 90% of the
      isolates tested are inhibited [MIC90], 0.015/1 microg/ml; 96% inhibited at a MIC
      of < or =1 microg/ml, 100% inhibited at a MIC of < or =2 microg/ml) and
      comparable to caspofungin (MIC50/MIC90, 0.03/0.25 mug/ml; 99% inhibited at a MIC
      of < or =2 microg/ml). Results by species, expressed as MIC50/MIC90 (micrograms
      per milliliter), were as follows: C. albicans, 0.015/0.03; C. glabrata,
      0.015/0.015; C. tropicalis, 0.03/0.06; C. krusei, 0.06/0.12; C. kefyr, 0.06/0.06;
      C. parapsilosis, 1/2; C. guilliermondii, 0.5/1; C. lusitaniae, 0.12/0.25; other
      Candida spp., 0.25/1. Although the species distribution varied considerably among
      the different geographic regions, there was no difference in micafungin activity
      across the regions. Micafungin has excellent in vitro activity against invasive
      clinical isolates of Candida from centers worldwide.

PMID- 17021080
TI  - Use of PCR and reverse line blot hybridization macroarray based on 16S-23S rRNA
      gene internal transcribed spacer sequences for rapid identification of 34
      mycobacterium species.
AB  - The aim of this study was to develop a PCR and reverse line blot hybridization
      (PCR-RLB) macroarray assay based on 16S-23S rRNA gene internal transcribed spacer
      sequences for the identification and differentiation of 34 mycobacterial species
      or subspecies. The performance of the PCR-RLB assay was assessed and validated by
      using 78 reference strains belonging to 55 Mycobacterium species, 219 clinical
      isolates which had been identified as mycobacteria by high-performance liquid
      chromatography or gas chromatography, three skin biopsy specimens from patients
      with suspected leprosy which had been shown to contain acid-fast bacilli, and
      isolates of 14 nonmycobacterial species. All mycobacteria were amplified in the
      PCR and hybridized with a genus-specific probe (probe MYC). The 34 species
      specific probes designed in this study hybridized only with the corresponding
      Mycobacterium species. The mycobacterial PCR-RLB assay is an efficient tool for
      the identification of clinical isolates of mycobacteria; it can reliably identify
      mixed mycobacterial cultures and M. leprae in skin biopsy specimens.

PMID- 17021081
TI  - Candida guilliermondii, an opportunistic fungal pathogen with decreased
      susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS
      DISK antifungal surveillance program.
AB  - Although a rare cause of invasive candidiasis, Candida guilliermondii has been
      reported to exhibit decreased susceptibility to antifungal agents. Aside from
      case reports and small surveys, there is little information regarding the
      epidemiology and antifungal susceptibility profile of C. guilliermondii. We
      report geographic and temporal trends in the isolation and antifungal
      susceptibilities of 1,029 C. guilliermondii clinical isolates collected from 127
      medical centers as part of the ARTEMIS DISK Antifungal Surveillance Program. In
      addition, we report the in vitro susceptibility of 132 bloodstream isolates of C.
      guilliermondii to caspofungin. C. guilliermondii represented 1.4% of the 75,761
      isolates collected from 2001 to 2003 and was most common among isolates from
      Latin America (3.7% versus 0.6 to 1.1%). Decreased susceptibility to fluconazole
      was noted (75% susceptible; range, 68 to 77% across regions), and voriconazole
      was more active in vitro against C. guilliermondii than fluconazole (91%
      susceptible; range, 88 to 93% across regions). Fluconazole was least active
      against isolates from dermatology (58%) and surgical (69%) services and against
      isolates associated with skin and soft tissue infection (68%, compared to 85%
      susceptible for bloodstream isolates). There was no evidence of increasing azole
      resistance over time among C. guilliermondii isolates tested from 2001 to 2003.
      Of 132 bloodstream isolates of C. guilliermondii tested against caspofungin, most
      were inhibited by < or =2 microg/ml (96%; MIC50/MIC90, 0.5/1.0 microg/ml). C.
      guilliermondii, a species that exhibits reduced susceptibility to fluconazole, is
      the sixth most frequently isolated Candida species from this large survey and may
      be an emerging pathogen in Latin America.

PMID- 17021082
TI  - Preparation of His-tagged armored RNA phage particles as a control for real-time
      reverse transcription-PCR detection of severe acute respiratory syndrome
      coronavirus.
AB  - Armored RNA has been increasingly used as both an external and internal positive
      control in nucleic acid-based assays for RNA virus. In order to facilitate
      armored RNA purification, a His6 tag was introduced into the loop region of the
      MS2 coat protein, which allows the exposure of multiple His tags on the surface
      during armored RNA assembly. The His-tagged armored RNA particles were purified
      to homogeneity and verified to be free of DNA contamination in a single run of
      affinity chromatography. A fragment of severe acute respiratory syndrome
      coronavirus (SARS-CoV) genome targeted for SARS-CoV detection was chosen for an
      external positive control preparation. A plant-specific gene sequence was chosen
      for a universal noncompetitive internal positive control preparation. Both
      controls were purified by Co2+ affinity chromatography and were included in a
      real-time reverse transcription-PCR assay for SARS-CoV. The noncompetitive
      internal positive control can be added to clinical samples before RNA extraction
      and enables the identification of potential inhibitive effects without
      interfering with target amplification. The external control could be used for the
      quantification of viral loads in clinical samples.

PMID- 17021083
TI  - Role of erythrocytes as a reservoir for ribavirin and relationship with adverse
      reactions in the early phase of interferon combination therapy for chronic
      hepatitis C virus infections.
AB  - We investigated the relationship between serum ribavirin concentrations and
      clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese
      patients with chronic hepatitis C virus infections treated with a 6-month course
      of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800
      mg/day) combination therapy. This randomized trial showed that the saturation of
      ribavirin uptake after taking ribavirin capsules does not occur within a dose
      range of 600 to 800 mg/day, which is a standard dosage used clinically in Japan.
      Serum ribavirin concentrations and clearance did not correlate with sustained
      virological response rates. Fourteen patients discontinued therapy because of
      adverse reactions, and sustained virological response rates were significantly
      reduced by discontinuation of therapy, while dose reduction of ribavirin did not
      alter the therapeutic effects. Ribavirin concentrations after 1 week and
      ribavirin clearance were significantly correlated with discontinuation of
      ribavirin; however, a multiple-regression analysis revealed that only hemoglobin
      concentration, but not ribavirin clearance, was a significant factor for
      discontinuation of therapy (odds ratio, 0.514; 95% confidence interval, 0.311 to
      0.85; P = 0.0095). It appears that peripheral erythrocytes may act as a reservoir
      for ribavirin and regulate serum ribavirin levels in the very early phase of
      treatment.

PMID- 17021084
TI  - Comparison of subtyping methods for differentiating Salmonella enterica serovar
      Typhimurium isolates obtained from food animal sources.
AB  - Molecular characterization (e.g., DNA-based typing methods) of Salmonella
      isolates is frequently employed to compare and distinguish clinical isolates
      recovered from animals and from patients with food-borne disease and nosocomial
      infections. In this study, we compared the abilities of different phenotyping and
      genotyping methods to distinguish isolates of Salmonella enterica serovar
      Typhimurium from different food animal sources. One hundred twenty-eight S.
      enterica serovar Typhimurium strains isolated from cattle, pigs, chickens, and
      turkeys or derived food products were characterized using pulsed-field gel
      electrophoresis (PFGE), repetitive element PCR (Rep-PCR), multilocus sequence
      typing (MLST), plasmid profiling, and antimicrobial susceptibility testing. Among
      the 128 Salmonella isolates tested, we observed 84 Rep-PCR profiles, 86 PFGE
      patterns, 89 MLST patterns, 36 plasmid profiles, and 38 susceptibility profiles.
      The molecular typing methods, i.e., PFGE, MLST, and Rep-PCR, demonstrated the
      best discriminatory power among Salmonella isolates. However, no apparent
      correlation was evident between the results of one molecular typing method and
      those of the others, suggesting that a combination of multiple methods is needed
      to differentiate S. enterica serovar Typhimurium isolates that genetically
      cluster according to one particular typing method.

PMID- 17021085
TI  - Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic
      and temporal trends from the ARTEMIS DISK antifungal surveillance program.
AB  - Candida rugosa is a fungus that appears to be emerging as a cause of infection in
      some geographic regions. We utilized the extensive database of the ARTEMIS DISK
      Antifungal Surveillance Program to describe the geographic and temporal trends in
      the isolation of C. rugosa from clinical specimens and the in vitro
      susceptibilities of 452 isolates to fluconazole and voriconazole. C. rugosa
      accounted for 0.4% of 134,715 isolates of Candida, and the frequency of isolation
      increased from 0.03% to 0.4% over the 6.5-year study period (1997 to 2003). C.
      rugosa was most common in the Latin American region (2.7% versus 0.1 to 0.4%).
      Decreased susceptibility to fluconazole (40.5% susceptible) was observed in all
      geographic regions; however, isolates from Europe and North America were much
      more susceptible (97 to 100%) to voriconazole than those from other geographic
      regions (55.8 to 58.8%). C. rugosa was most often isolated from blood and urine
      in patients hospitalized at the Medical and Surgical inpatient services. Notably,
      bloodstream isolates were the least susceptible to both fluconazole and
      voriconazole. C. rugosa should be considered, along with the established
      pathogens Candida krusei and Candida glabrata, as a species of Candida with
      reduced susceptibility to the azole antifungal agents.

PMID- 17021086
TI  - Longitudinal analysis of genotype distribution of influenza A virus from 2003 to
      2005.
AB  - Influenza A viruses cause yearly epidemics, in part, due to their ability to
      overcome immunity from previous infections through acquisition of mutations.
      Amino acid sequences encoded by genes 4 (HA), 6 (NA), 7 (M), and 8 (NS) from 77
      H3N2 influenza A isolates, collected between November 2003 and March 2005, were
      analyzed to determine the extent to which the viruses mutated within epidemic
      periods and between the epidemics. Nucleotide and amino acid sequences were
      stable throughout the epidemics but experienced substantial changes between
      epidemics. Major changes occurred in the HA gene in 5 to 7 amino acids and the NA
      gene in 11 to 13 amino acids and changes of 5 amino acids occurred in the M and
      NS genes. In the HA gene, changes occurred in sites known to be epitopes that
      determine the hemagglutination inhibition reactivity, and these were shown to be
      associated with a change of strain from A/Fujian/411/2002-like to
      A/California/7/2004-like viruses. Our findings indicate that genotype
      determination promises to be a rapid approach for detecting new strains of
      influenza A viruses in a population.

PMID- 17021087
TI  - Multiplex real-time PCR assay for simultaneous detection of Acanthamoeba spp.,
      Balamuthia mandrillaris, and Naegleria fowleri.
AB  - Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia
      mandrillaris occur throughout the world and pose many diagnostic challenges. To
      date, at least 440 cases of severe central nervous system infections caused by
      these amebas have been documented worldwide. Rapid and specific identification of
      these free-living amebas in clinical samples is of crucial importance for
      efficient case management. We have developed a triplex real-time TaqMan PCR assay
      that can simultaneously identify Acanthamoeba spp., B. mandrillaris, and N.
      fowleri in the same PCR vessel. The assay was validated with 22 well
      characterized amebic strains harvested from cultures and nine clinical specimens
      that were previously characterized by in vitro culture and/or immunofluorescence
      assay. The triplex assay demonstrated high specificity and a rapid test
      completion time of less than 5 h from the reception of the specimen in the
      laboratory. This assay was able to detect one single ameba per sample analyzed,
      as determined with cerebrospinal fluid spiked with diluted cultured amebas. This
      assay could become useful for fast laboratory diagnostic assessment of amebic
      infections (caused by free-living amebas) in laboratories with adequate
      infrastructure to perform real-time PCR testing.

PMID- 17021088
TI  - Enumeration of bacterial cell numbers and detection of significant bacteriuria by
      use of a new flow cytometry-based device.
AB  - A new, automated flow cytometry-based urine bacterium analyzer (UBA) was
      developed. We assessed the UBA for linearity of measurement, reproducibility of
      results, carryover rate, and correlation of measured results with those
      determined by urine culture. We also evaluated its ability to screen urine
      samples for significant bacteriuria. The UBA showed excellent linearity and a
      minor carryover rate. Results from the UBA were highly reproducible, and in
      between-run precision assays, the coefficients of variation for the UBA results
      were smaller than those for the urine culture results. Two hundred seventy-three
      urine specimens from patients attending the outpatient clinics of two university
      based hospitals were examined. The results for the UBA were compared with those
      for urine culture. The UBA detected significant bacteriuria with a sensitivity of
      96.6%, a specificity of 79.9%, a positive predictive value of 57.0%, a negative
      predictive value of 98.8%, a false-positive rate of 15.8%, a false-negative rate
      of 0.7%, and an accuracy of 83.5%. These results were comparable to or better
      than those obtained with previously reported screening procedures. The UBA can
      perform accurate enumeration of bacterial cells automatically in 90 seconds and
      can be used for the screening of significant bacteriuria.

PMID- 17021089
TI  - Expertise of laboratories in viral load quantification, genotyping, and precore
      mutant determination for hepatitis B virus in a multicenter study.
AB  - A national evaluation study was performed in 14 specialized laboratories with the
      objective of assessing their capacities to provide (i) hepatitis B virus (HBV)
      viral loads (VL), (ii) HBV genotypes, and(iii) identification of precore/core
      mutants. The panel consisted of 12 HBV DNA-positive samples with VLs from 2.8 to
      9.1 log(10) copies/ml, different HBV genotypes (A to F), and 3 mutant and 9 wild
      type samples at nucleotide 1896. The coefficients of variation of the mean VLs
      ranged from 2.4% to 10.4% with the Cobas HBV Monitor assay, from 1.8% to 5.5%
      with the Cobas TaqMan 48, from 1.5 to 26.2% with RealArt HBV PCR, and from 0 to
      7% with branched DNA (bDNA). The Cobas Monitor assay underestimated the VLs of
      genotype F samples, with differences ranging from 1.4 to 2.4 log(10) copies/ml.
      The accuracies of genotype determinations ranged from 33% to 100%, and those of
      precore mutant determinations ranged from 25 to 100%. This study showed some
      drawbacks of two widely used assays: (i) Cobas Monitor has a narrow dynamic range
      and underestimates genotype F sample VLs and (ii) bDNA shows poor sensitivity and
      may fail to identify patients with low VLs. With higher performance in terms of
      analytical sensitivity combined with a larger dynamic range and an ability to
      quantify the main genotypes equally, real-time PCR methods appear more
      appropriate for accurate monitoring of HBV DNA quantification. Furthermore, the
      clinical implications of HBV genotyping and the determination of precore/core
      mutants need to be clearly stated to justify the standardization of these
      methods.

PMID- 17021090
TI  - Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple
      hospitals in London and Southeast England.
AB  - From late 2003 to the end of 2005, the Health Protection Agency's national
      reference laboratories received approximately 1,600 referrals of Acinetobacter
      spp., including 419 and 58 examples, respectively, of two carbapenem-resistant
      Acinetobacter baumannii lineages, designated OXA-23 clones 1 and 2.
      Representatives of these clones were obtained from 40 and 8 hospitals,
      respectively, in London or elsewhere in Southeast England. Both clones had blaOXA
      23-like genes, as well as the intrinsic (but downregulated) blaOXA-51-like
      carbapenemase genes typical of A. baumannii. Both were highly multiresistant:
      only colistin and tigecycline remained active versus OXA-23 clone 1 isolates; OXA
      23 clone 2 isolates were also susceptible to amikacin and minocycline. These
      lineages increase the burden created by the southeast (SE) clone, a previously
      reported A. baumannii lineage with variable carbapenem resistance contingent on
      upregulation of the blaOXA-51-like gene. Known since 2000, the SE clone had been
      referred from over 40 hospitals by the end of 2005, with 627 representatives
      received by the reference laboratories. The OXA-23 clone 2 is now in decline, but
      OXA-23 clone 1 continues to be referred from new sites, as does the SE clone.
      Their spread is forcing the use of unorthodox therapies, principally colistin and
      tigecycline, although the optimal regimens remain uncertain.

PMID- 17021091
TI  - Denaturing gradient gel electrophoresis as a diagnostic tool in periodontal
      microbiology.
AB  - Bacteria play an important role in the initiation and progression of periodontal
      diseases and are part of a biofilm, which can contain over 100 different species.
      The aim of the present study was to show the potential of denaturing gradient gel
      electrophoresis (DGGE) as a tool for the detection of clinically relevant species
      and to compare the results of detection by DGGE with those by PCR and culturing.
      Hybridization of the bands from the DGGE profiles with species-specific probes
      was developed to confirm the band positions in the marker obtained with reference
      strains. The sensitivities of DGGE compared to those of cultivation for the
      detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, and Tannerella forsythensis were 100, 100, 88, and 100%,
      respectively; and the sensitivities of DGGE compared to those of PCR were 100,
      90, 88, and 96%, respectively. DGGE as a diagnostic tool could easily be extended
      to other species, as shown for Treponema denticola, which could be detected in
      48% of the samples. Three different groups of A. actinomycetemcomitans serotypes
      could be distinguished by DGGE (i.e., a group comprising serotypes a, d, e, and
      f; a group comprising serotype b; and a group comprising serotype c). Amplicons
      from P. gingivalis and T. denticola migrated to the same position in the gel, and
      P. intermedia produced multiple bands. In the present study we show that the DGGE
      profiles represent clinically relevant species which can be detected by
      hybridization with species-specific probes. With DGGE, large numbers of samples
      can be analyzed for different species simultaneously, and DGGE may be a good
      alternative in periodontal microbial diagnostics.

PMID- 17021092
TI  - Accuracy of cefoxitin disk testing for characterization of oxacillin resistance
      mediated by penicillin-binding protein 2a in coagulase-negative staphylococci.
AB  - The Clinical and Laboratory Standards Institute (CLSI) proposed, beginning in
      2004, the use of cefoxitin disks to predict resistance mediated by the mecA gene
      in all species of coagulase-negative staphylococci (CoNS). The aim of this work
      was to evaluate the efficiency of the cefoxitin disk and of oxacillin-salt agar
      screening (MHOX) to characterize the oxacillin resistance mediated by the mecA
      gene in CoNS. One hundred seven CoNS isolates from different clinical samples
      were studied. Detection of the mecA gene by PCR was considered the "gold
      standard." The susceptibility to oxacillin and cefoxitin was detected by the disk
      diffusion and agar dilution tests, as described by the CLSI. MHOX was also
      performed with 6 microg/ml of oxacillin and 4% NaCl. The sensitivities of the
      oxacillin and cefoxitin disks for all CoNS species were 88% and 80%,
      respectively, whereas the specificities were 63% and 100%, respectively. The
      sensitivities of the agar dilution test for oxacillin and cefoxitin (for proposed
      breakpoints of > or =4 microg/ml for resistance and < or =2 microg/ml for
      susceptibility) were 90% and 85%, respectively, whereas the specificities were
      76% and 98%, respectively. MHOX showed a sensitivity of 90% and a specificity of
      95% for all CoNS species. Both the MHOX and the cefoxitin disk results indicate
      that these are appropriate methods for the evaluation of oxacillin resistance
      mediated by the mecA gene in all CoNS species.

PMID- 17021093
TI  - Candida albicans strain maintenance, replacement, and microvariation demonstrated
      by multilocus sequence typing.
AB  - We typed 165 Candida albicans isolates from 44 different sources by multilocus
      sequence typing (MLST) and ABC typing of rRNA genes and determined their
      homozygosity or heterozygosity at the mating-type-like locus (MTL). The isolates
      represented pairs or larger sets from individual sources, which allowed the
      determination of strain diversity within patients. A comparison of replicate
      sequence data determined a reproducibility threshold for regarding isolates as
      MLST indistinguishable. For 36 isolate sets, MLST and ABC typing showed
      indistinguishable or highly related strain types among isolates from different
      sites or from the same site at different times from each patient. This
      observation included 11 sets with at least one isolate from a blood culture and a
      nonsterile site from the same patient. For one patient, strain replacement was
      evidenced in the form of two sets of isolates from different hospital admissions
      where the strain types within each set were nearly identical but where the two
      sets differed both by MLST and ABC typing. MLST therefore confirms the existing
      view of C. albicans strain carriage. Microvariation, evidenced as small
      differences between MLST types, resulted in most instances from a loss of
      heterozygosity at one or more of the sequenced loci. Among isolate sets that
      showed major strain type differences, some isolates could be excluded as likely
      examples of handling errors during storage. However, for a minority of isolates,
      intermittent differences in ABC type for tightly clustered MLST types and
      intermittent appearances of MTL homozygosity lead us to propose that some C.
      albicans isolates, or all isolates under yet-to-be-determined conditions,
      maintain a high level of genetic diversity by mechanisms such as recombination,
      gene conversion, or chromosomal ploidy change.

PMID- 17021094
TI  - Performance of the genotype MTBDR line probe assay for detection of resistance to
      rifampin and isoniazid in strains of Mycobacterium tuberculosis with low- and
      high-level resistance.
AB  - We assessed the performance of the Genotype MTBDR line probe assay that offers
      the simultaneous identification of Mycobacterium tuberculosis and its resistance
      to rifampin (RIF) and isoniazid (INH) by detecting the most commonly found
      mutations in the rpoB and katG genes. One hundred thirteen M. tuberculosis
      isolates were tested. The nucleotide sequences of the katG and inhA genes and the
      mabA-inhA promoter region were also determined. The MTBDR assay detected 100% and
      67% (n = 64) of the strains resistant to RIF and INH, respectively. Among the
      latter, 62 strains carried a Ser315Thr mutation in katG, 59 of them displaying a
      high level of resistance to INH. Two strains with a low level of INH resistance
      had a Ser315Asn mutation. No mutation was found by the MTBDR assay for 31 INH
      resistant strains (33%), of which 24 showed a low level of resistance. By DNA
      sequencing, we found among them various mutations in the KatG protein for 7
      strains, a C-->T mutation in position -15 of the mabA-inhA promoter in 17
      strains, and a Ser94Ala mutation in InhA for 7 strains. In conclusion, the MTBDR
      assay, which fits easily in the workflow of a routine laboratory, enabled the
      detection of 100% of the RIF-resistant strains and 89% of the INH-resistant
      strains with a high level of resistance but only 17% of the strains characterized
      by a low level of INH resistance, indicating that the test can be used as a rapid
      method to detect in the same experiment the rifampin-resistant and the high-level
      isoniazid-resistant strains of M. tuberculosis.

PMID- 17021095
TI  - Changes in periodontal health status are associated with bacterial community
      shifts as assessed by quantitative 16S cloning and sequencing.
AB  - The gingival sulcus contains a complex ecosystem that includes many uncultivated
      bacteria. Understanding the dynamics of this ecosystem in transitions between
      health and disease is important in advancing our understanding of the bacterial
      etiology of periodontitis. The objective of this longitudinal study was to
      examine the stability of bacterial colonization in the gingival crevice and to
      explore the relationship between shifts in microbial composition and changes in
      periodontal health status using a comprehensive, quantitative, culture
      independent approach. Subgingival plaque samples and periodontal data were
      collected from 24 subjects over 2 years. Baseline and 2-year plaque samples were
      analyzed using quantitative ribosomal 16S cloning and sequencing. Ten subjects
      remained periodontally healthy over 2 years, the periodontal health of seven
      subjects worsened, and seven subjects showed clinical improvement. Bacterial
      stability was greatest among healthy, clinically stable subjects and lowest for
      subjects whose periodontal status worsened (P = 0.01). Higher numbers of species
      lost or gained were also observed for subjects whose clinical status changed (P =
      0.009). This provides evidence that a change in periodontal status is accompanied
      by shifts within the bacterial community. Based on these data, measures of
      microbial stability may be useful in clinical diagnosis and prognosis. Regarding
      individual species, increases in levels of the uncultivated phylotype Veillonella
      sp. oral clone X042, a gram-negative bacterium and the most common member of the
      subgingival bacterial community, were associated with periodontal health (P =
      0.04), suggesting that this is an important beneficial species. Filifactor
      alocis, a gram-positive anaerobe, was found at higher levels in subjects with
      disease (P = 0.01).

PMID- 17021096
TI  - Development of an enzyme immunoassay for detection of sapovirus-specific
      antibodies and its application in a study of seroprevalence in children.
AB  - Sapoviruses (SVs) are an important cause of acute pediatric gastroenteritis. Due
      to the lack of appropriate diagnostic methods, the epidemiology of SV-associated
      illness remains poorly understood. Baculovirus and Escherichia coli expression
      systems were evaluated for the development of antibody detection enzyme
      immunoassays (EIA). Age-related antibody prevalence in children was studied using
      the new EIA. Because of the low yield of the baculovirus system, the E. coli
      expressed SV capsid proteins were used to develop the EIA. The antigenic
      specificities of the E. coli-expressed SV capsid proteins were demonstrated using
      hyperimmune antisera raised in animals and sera collected from patients. A high
      prevalence (>90%) of antibodies to both SV (strain Mex340) and norovirus (strain
      VA387) was observed in children involved in a birth cohort at 20 to 24 months of
      age; however, at 1 to 3 months of age, <25% of the children possessed anti-SV
      antibodies versus >90% with anti-NV antibodies. The E. coli-derived SV proteins
      are an excellent source of antigens for the EIA. SV infection is common in the
      first 2 years of life. The low prevalence of maternal antibodies detected in
      Mexican children against SVs in this study is unique and needs to be addressed in
      future studies.

PMID- 17021097
TI  - Cross-sectional comparison of an automated hybrid capture 2 assay and the
      consensus GP5+/6+ PCR method in a population-based cervical screening program.
AB  - In this cross-sectional study, clinical performances of the hybrid capture 2
      assay using an automated instrument (i.e., rapid capture system) (hc2-RCS) and
      the high-risk human papillomavirus GP5+/6+ PCR-enzyme immunoassay (EIA) test were
      compared using cervical scrape specimens from 8,132 women that participated in a
      population-based screening trial. The hc2-RCS test scored significantly more
      samples positive (6.8%) than the GP5+/6+ PCR-EIA (4.8%) (P < 0.0005). This could
      be attributed largely to a higher positivity rate by the hc2-RCS test for women
      with cytologically normal, borderline, or mild dyskaryosis. A receiver operator
      characteristics analysis of the semiquantitative hc2-RCS results in relation to
      different cytology categories revealed that these differences are owing to
      differences in assay thresholds. For women classified as having moderate
      dyskaryosis or worse who also had underlying histologically confirmed cervical
      intraepithelial neoplasia grade 3 or cervical cancer (> or =CIN3), the hc2-RCS
      scored 97% (31/32) of samples positive, versus 91% (29/32) by GP5+/6+ PCR-EIA.
      However, this difference was not significant (P = 0.25). After increasing the hc2
      RCS cutoff from 1.0 to 2.0 relative light units/cutoff value of the HPV16
      calibrator (RLU/CO), no additional CIN3 lesions were missed by hc2-RCS, but the
      number of test-positive women with normal, borderline, or mild dyskaryosis was
      significantly decreased (P < 0.0005). However, at this RLU/CO, the difference in
      test positivity between hc2-RCS and the GP5+/6+ PCR-EIA was still significant (P
      = 0.02). The use of an RLU/CO value of 3.0 revealed no significant difference
      between hc2-RCS and GP5+/6+ PCR-EIA results, and equal numbers of smears
      classified as > or =CIN3 (i.e., 29/32) were detected by both methods. In summary,
      both assays perform very well for the detection of >or =CIN3 in a population
      based cervical screening setting. However, adjustment of the hc2-RCS threshold to
      an RLU/CO value of 2.0 or 3.0 seems to produce an improved balance between the
      clinical sensitivity and specificity for > or =CIN3 in population-based cervical
      screening.

PMID- 17021098
TI  - Molecular epidemiology of G9 rotaviruses in Taiwan between 2000 and 2002.
AB  - Since the mid-1990s, novel G9 rotaviruses have been detected in many countries,
      suggesting that G9 is a globally important serotype. The molecular epidemiology
      of G9 rotaviruses in Taiwan from 2000 to 2002 was investigated in this study. G9
      rotavirus first appeared in 2000 with 4 cases and constituted 33.8% and 54.8% of
      the rotavirus-positive samples in 2001 and 2002, respectively. These G9 strains
      belonged to P[8]G9, subgroup II, and long electropherotype, except one belonged
      to P[4]G9, subgroup II, and short electropherotype. Nucleotide sequencing and
      phylogenetic analysis of 52 Taiwanese G9 rotaviruses showed that the VP7 genes
      shared a high degree of identity to overseas G9 rotaviruses detected after 1993
      and that the VP8* portions of the VP4 genes were more closely related to those of
      local rotaviruses of other G types. The two P[8]G9 strains with high nucleotide
      identities in the VP7 and the partial VP4 genes, 01TW591 of Taiwan from 2001 and
      95H115 of Japan from 1995, varied in four genes, genes 2, 3, 7, and 8, which was
      revealed by RNA-RNA hybridization. Representative strains for different RNA
      patterns were also analyzed in the partial VP2 and VP3 genes; the nucleotide
      identities were high between Taiwanese G9 strains and local G3 or G2 strains.
      These results suggested that Taiwanese G9 rotaviruses possibly had evolved
      through reassortment between overseas G9 strains and circulating rotaviruses of
      other G types.

PMID- 17021099
TI  - Molecular epidemiology of norovirus outbreaks in Norway during 2000 to 2005 and
      comparison of four norovirus real-time reverse transcriptase PCR assays.
AB  - During the period from January 2000 to August 2005 a total of 204 outbreaks of
      norovirus gastroenteritis were diagnosed at the Norwegian Institute of Public
      Health. A clear increase in the norovirus activity was seen in healthcare
      institutions during the winter seasons. Polymerase sequence analysis of norovirus
      strains from 122 outbreaks showed that 112 were caused by GII strains (91.8%).
      Two norovirus variants seen during the study period-GIIb and GII.4-were
      predominant between January 2000 and September 2002, whereas GII.4 was
      predominant from September 2002 onward. The highest norovirus activity was seen
      during the 2002-2003 and 2004-2005 seasons with the emergence of new GII.4
      variants. This study describes the molecular epidemiology of norovirus strains
      circulating in Norway during the five previous seasons and compares four
      norovirus real-time reverse transcriptase PCR assays. A suitable assay for
      routine diagnostics is suggested.

PMID- 17021100
TI  - Identification of virulence genes linked with diarrhea due to atypical
      enteropathogenic Escherichia coli by DNA microarray analysis and PCR.
AB  - The role of atypical enteropathogenic Escherichia coli (EPEC) in childhood
      diarrhea is controversial. The aim of the present study was to search for genes
      linked with diarrhea in atypical EPEC strains from a case-control study among
      Norwegian children. Using DNA microarray analysis, genomic DNAs from strains
      isolated from children with (n = 37) and without (n = 20) diarrhea were
      hybridized against 242 different oligonucleotide probes specific for 182
      virulence genes or markers from all known E. coli pathotypes. PCR was performed
      to test the strains for seven putative virulence genes not included in the
      microarray panel. The OI-122 gene efa1/lifA was the gene with the strongest
      statistical association with diarrhea (P = 0.0008). Other OI-122 genes (set/ent,
      nleB, and nleE) and genes with other locations (lpfA, paa, ehxA, and ureD) were
      also associated with diarrheal disease. The phylogenetic marker gene yjaA was
      negatively associated with diarrhea (P = 0.0004). Atypical EPEC strains could be
      classified in two main virulence groups based on their content of OI-122, lpfA,
      and yjaA genes. Among children with diarrhea, atypical EPEC isolates belonging to
      virulence group I (OI-122 and lpfA positive, yjaA negative) were the most common,
      while the majority of isolates from healthy children were classified as virulence
      group II strains (OI-122 negative, lpfA and yjaA positive; P < 0.001). In
      conclusion, using DNA microarray analysis to determine the virulence gene profile
      of atypical EPEC isolates, several genes were found to be significantly
      associated with diarrhea. Based on their composition of virulence genes, the
      majority of strains could be classified in two virulence groups, of which one was
      seen mainly in children with diarrhea.

PMID- 17021101
TI  - Staphylococcus aureus genotyping using novel real-time PCR formats.
AB  - One approach to microbial genotyping is to make use of sets of single-nucleotide
      polymorphisms (SNPs) in combination with binary markers. Here we report the
      modification and automation of a SNP-plus-binary-marker-based approach to the
      genotyping of Staphylococcus aureus and its application to 391 S. aureus isolates
      from southeast Queensland, Australia. The SNPs used were arcC210, tpi243,
      arcC162, gmk318, pta294, tpi36, tpi241, and pta383. These provide a Simpson's
      index of diversity (D) of 0.95 with respect to the S. aureus multilocus sequence
      typing database and define 61 genotypes and the major clonal complexes. The
      binary markers used were pvl, cna, sdrE, pT181, and pUB110. Two novel real-time
      PCR formats for interrogating these markers were compared. One of these makes use
      of "light upon extension" (LUX) primers and biplexed reactions, while the other
      is a streamlined modification of kinetic PCR using SYBR green. The latter format
      proved to be more robust. In addition, automated methods for DNA template
      preparation, reaction setup, and data analysis were developed. A single SNP-based
      method for ST-93 (Queensland clone) identification was also devised. The
      genotyping revealed the numerical importance of the "South West Pacific" and
      "Queensland" community-acquired methicillin-resistant S. aureus (MRSA) clones and
      the clonal complex 239 "Aus-1/Aus-2" hospital-associated MRSA. There was a strong
      association between the community-acquired clones and pvl.

PMID- 17021102
TI  - Use of a single-nucleotide polymorphism genotyping system to demonstrate the
      unique epidemiology of methicillin-resistant Staphylococcus aureus in remote
      aboriginal communities.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has
      emerged as a major public health problem in Australia, as in many other parts of
      the world. High rates of CA-MRSA skin and soft tissue infection have been
      reported from Aboriginal communities. We used a single-nucleotide polymorphism
      (SNP) genotyping typing system based on the multilocus sequence type (MLST)
      database to investigate the epidemiology of CA-MRSA and methicillin-sensitive S.
      aureus (MSSA) over a 12-month period in three remote Aboriginal communities of
      Northern Australia. This was supplemented by real-time PCR for Panton-Valentine
      leukocidin (PVL) genes, staphylococcal cassette chromosome mec (SCCmec) typing,
      and antimicrobial susceptibility testing. S. aureus was recovered from pyoderma
      lesions on 221 occasions and throat swabs on 44 occasions. The median monthly
      recovery rate of S. aureus from skin sores was 58% (interquartile range, 62 to
      78%), and there was no seasonal variation. Twenty-three percent of isolates were
      CA-MRSA; the proportion was similar across the communities and did not vary over
      the study period. Erythromycin resistance was found in 47% of CA-MRSA and 21% of
      MSSA. SNP-based typing identified 14 different clonal complexes (cc); however,
      cc75 was predominant, accounting for 71% of CA-MRSA isolates. These were
      confirmed as ST75-like by using an additional SNP and MLST of selected isolates.
      All but one of the cc75 isolates had SSCmec type IV (one had type V), and all
      were PVL negative. Monthly tracking of SNP-based cc types showed a highly dynamic
      process. ST75-MRSA-IV appears to be unique to the region and probably evolved de
      novo in remote Aboriginal communities.

PMID- 17021103
TI  - Use of a multiantigen detection algorithm for diagnosis of Kaposi's sarcoma
      associated herpesvirus infection.
AB  - The ability to readily and accurately diagnose Kaposi's sarcoma-associated
      herpesvirus (KSHV, or human herpesvirus 8) infection in individuals remains a
      demanding task. Among the available diagnostic methods, sensitivities and
      specificities range widely, and many are inadequate for large-scale screening
      studies. We examined a serological algorithm for detecting KSHV in human sera
      having high sensitivity and specificity. This method uses previously described
      open reading frame (ORF) K8.1 and ORF65 peptide-based enzyme-linked immunosorbent
      assays and a novel purified recombinant full-length LANA1 protein. We generated
      two multiantigen algorithms: one that maximized sensitivity and one that
      maximized specificity. These serological algorithms were then used to evaluate
      seroprevalence rates among populations of clinical and epidemiological
      importance. The serological algorithms yielded sensitivities of 96% and 93% and
      specificities of 94% and 98% for the more sensitive and specific algorithms,
      respectively. Among kidney donors, seroprevalence was low, 4.0% (2/50), and
      similar to that of blood donors (P = 0.46; odds ratio [OR], 1.4; confidence
      interval [CI], 0.14 to 7.9) using the highly specific algorithm. Using the
      sensitive algorithm, 8.0% (4/50) were infected compared to 6.4% (16/250) observed
      among blood donors (OR, 1.3; CI, 0.41 to 4.0; P = 0.43). Among subjects requiring
      bone marrow transplantation, seroprevalence rates were not elevated compared to
      those of blood donors (OR, 2.0; 95% CI, 0.10 to 122.9; P = 0.50). Because the
      need for high-quality KSHV detection methods are warranted and because questions
      remain about the optimal methods for assessing KSHV infection in individuals, we
      propose a systematic approach to standardize and optimize the assessment of KSHV
      infection rates using a combination of established and novel serological assays
      and methods.

PMID- 17021104
TI  - Novel method to identify source-associated phylogenetic clustering shows that
      Listeria monocytogenes includes niche-adapted clonal groups with distinct
      ecological preferences.
AB  - While phylogenetic and cluster analyses are often used to define clonal groups
      within bacterial species, the identification of clonal groups that are associated
      with specific ecological niches or host species remains a challenge. We used
      Listeria monocytogenes, which causes invasive disease in humans and different
      animal species and which can be isolated from a number of environments including
      food, as a model organism to develop and implement a two-step statistical
      approach to the identification of phylogenetic clades that are significantly
      associated with different source populations, including humans, animals, and
      food. If the null hypothesis that the genetic distances for isolates within and
      between source populations are identical can be rejected (SourceCluster test),
      then particular clades in the phylogenetic tree with significant
      overrepresentation of sequences from a given source population are identified
      (TreeStats test). Analysis of sequence data for 120 L. monocytogenes isolates
      revealed evidence of clustering between isolates from the same source, based on
      the phylogenies inferred from actA and inlA (P = 0.02 and P = 0.07, respectively;
      SourceCluster test). Overall, the TreeStats test identified 10 clades with
      significant (P < 0.05) or marginally significant (P < 0.10) associations with
      defined sources, including human-, animal-, and food-associated clusters.
      Epidemiological and virulence phenotype data supported the fact that the source
      associated clonal groups identified here are biologically valid. Overall, our
      data show that (i) the SourceCluster and TreeStats tests can identify
      biologically meaningful source-associated phylogenetic clusters and (ii) L.
      monocytogenes includes clonal groups that have adapted to infect specific host
      species or colonize nonhost environments.

PMID- 17021105
TI  - Genotyping of measles virus in clinical specimens on the basis of oligonucleotide
      microarray hybridization patterns.
AB  - An oligonucleotide microarray hybridization method for identification of most
      known measles virus (MV) genotypes was developed. Like the conventional
      genotyping method, the microarray relied on detecting sequence differences in the
      450-nucleotide region coding for the COOH-terminal 150 amino acids of the
      nucleoprotein (N). This region was amplified using PCR primers binding to all
      known MV genotypes. The microarray included 71 pairs of oligonucleotide probes
      (oligoprobes) immobilized on glass slides. Each pair consisted of a genotype
      specific oligoprobe, which matched the sequence of only one target genotype, and
      a control oligoprobe, which contained mismatches at the nucleotide positions
      unique to this genotype. A pattern recognition algorithm based on cluster
      analysis of the ratios of hybridization signals from specific and control
      oligoprobes was used to identify the specific MV genotype. Following the initial
      validation, the method was used for rapid genotyping of two panels of coded
      samples. The results of this study showed good sensitivity (90.7%), specificity
      (100%), and genotype agreement (91.8%) for the new method compared to the results
      of genotyping conducted using phylogenetic analysis of viral sequences of the C
      terminus of the N gene. In addition, the microarray demonstrated the ability to
      identify potential new genotypes of MV based on the similarity of their
      hybridization patterns with those of known MV genotypes.

PMID- 17021106
TI  - Evaluation of peptide nucleic acid-fluorescence in situ hybridization for
      identification of clinically relevant mycobacteria in clinical specimens and
      tissue sections.
AB  - With fluorescently labeled PNA (peptide nucleic acid) probes targeting 16S rRNA,
      we established a 3-h fluorescence in situ hybridization (FISH) procedure for
      specific visualization of members of the Mycobacterium tuberculosis complex, M.
      leprae, M. avium, and M. kansasii. Probe specificity was tested against a panel
      of 25 Mycobacterium spp. and 10 gram-positive organisms. After validation, probes
      were used to identify 52 mycobacterial culture isolates. Results were compared to
      conventional genotypic identification with amplification-based methods. All
      isolates (M. tuberculosis complex, n = 24; M. avium, n = 7; M. kansasii, n = 1)
      were correctly identified by FISH. In addition, the technique was used
      successfully for visualization of mycobacteria in biopsies from infected humans
      or animals. In conclusion, PNA-FISH is a fast and accurate tool for species
      specific identification of culture-grown mycobacteria and for direct
      visualization of these organisms in tissue sections. It may be used successfully
      for both research and clinical microbiology.

PMID- 17021108
TI  - Contemporary prevalence of BRO beta-lactamases in Moraxella catarrhalis: report
      from the SENTRY antimicrobial surveillance program (North America, 1997 to 2004).
AB  - A total of 7,860 community-acquired Moraxella catarrhalis isolates (SENTRY
      Antimicrobial Surveillance Program, 1997 to 2004) were tested by broth
      microdilution methods, and 399 randomly selected strains from North American
      sites were tested for BRO-1 and BRO-2 by PCR methods. Several antimicrobials
      remained very active, including amoxicillin-clavulanate (MIC90s, < or =0.25
      microg/ml), azithromycin (MIC90s, < or =0.12 microg/ml), ceftriaxone (MIC90s, 0.5
      microg/ml), and levofloxacin (MIC90s, < or =0.03 to 0.06 microg/ml). The BRO-2
      incidence rates by year were 3 to 4% overall (96 to 97% for BRO-1) and were the
      highest in Canada (7.9%), with the incidence in the United States being only
      2.0%.

PMID- 17021107
TI  - Design, construction, and evaluation of a specific chimeric antigen to diagnose
      chagasic infection.
AB  - Chagas' disease is routinely diagnosed by detecting specific antibodies (Abs)
      using serological methods. The methodology has the drawback of potential cross
      reactions with Abs raised during other infectious and autoimmune diseases (AID).
      Fusion of DNA sequences encoding antigenic proteins is a versatile tool to
      engineer proteins to be used as sensitizing elements in serological tests. A
      synthetic gene encoding a chimeric protein containing the C-terminal region of
      C29 and the N-terminal region of TcP2beta was constructed. A 236-serum panel,
      composed of 104 reactive and 132 nonreactive sera to Chagas' disease, was used to
      evaluate the performance of the chimera. Among the nonreactive sera, 65 were from
      patients with AID (systemic lupus erythematosus and rheumatoid arthritis) or
      patients infected with Leishmania brasiliensis, Brucella abortus, Streptococcus
      pyogenes, or Toxoplasma gondii. The diagnostic performances of the complete
      TcP2beta (TcP2betaFL) and its N-terminal region (TcP2betaN) were evaluated.
      TcP2betaFL showed unspecific recognition toward leishmaniasis (40%) and AID Abs
      (58%), while TcP2betaN showed no unspecific recognition. The diagnostic utility
      of the chimera was evaluated by analyzing reactivity and comparing the results
      with those obtained with TcP2betaN. The chimera reactivity was higher than that
      of the peptide fractions (0.874 versus 0.564 optical density, P = 0.0017). The
      detectability and specificity were both 100% for the whole serum panel tested. We
      conclude that the obtained chimera shows an improved selectivity and sensitivity
      compared with other ones previously reported, therefore displaying an optimized
      performance for Trypanosoma cruzi infection diagnosis.

PMID- 17021109
TI  - Identification of Borrelia burgdorferi ribosomal protein L25 by the phage surface
      display method and evaluation of the protein's value for serodiagnosis.
AB  - The phage surface display technique was used to identify Borrelia burgdorferi
      antigens. By affinity selection with immunoglobulin G from pooled sera of six
      Lyme borreliosis (LB) patients, the ribosomal protein L25 was identified. The
      diagnostic value of L25 was investigated by an enzyme-linked immunosorbent assay,
      using sera from 80 LB patients and 75 controls, and the use of the protein
      resulted in a specificity of 99% and a 23% sensitivity, which qualify L25 as a
      useful antigen when combined with others.

PMID- 17021110
TI  - Age dependence of adenovirus-specific neutralizing antibody titers in individuals
      from sub-Saharan Africa.
AB  - We assessed neutralizing antibody titers to adenovirus serotype 5 (Ad5) and six
      rare adenovirus serotypes, serotypes 11, 35, 50, 26, 48, and 49, in pediatric
      populations in sub-Saharan Africa. We observed a clear age dependence of Ad5
      specific neutralizing antibody titers. These data will help to guide the
      development of Ad vector-based vaccines for human immunodeficiency virus type 1
      and other pathogens.

PMID- 17021111
TI  - Detection of norovirus antigens from recombinant virus-like particles and stool
      samples by a commercial norovirus enzyme-linked immunosorbent assay kit.
AB  - The commercial norovirus enzyme-linked immunosorbent assay kit was evaluated for
      its reactivity to recombinant virus-like particles and the detection of natural
      viruses from stool samples of Japanese infants and children with sporadic acute
      gastroenteritis compared to reverse transcription-PCR. The kit had a sensitivity
      of 76.3% and a specificity of 94.9%. Our results clearly indicated that the kit
      allows the detection of the most prevalent genotype, GII/4. In order to increase
      the sensitivity of the kit, the reactivity with norovirus of GII/3 and GII/6
      genotypes needs to be improved.

PMID- 17021112
TI  - Unusually high prevalence of nosocomial Panton-Valentine leukocidin-positive
      Staphylococcus aureus isolates in Cape Verde Islands.
AB  - Characterization of nosocomial methicillin-susceptible Staphylococcus aureus
      isolates from Cape Verde showed that (i) Panton-Valentine leukocidin genes were
      present in 35% of the isolates and (ii) half of the collection had the same
      genetic background as methicillin-resistant pandemic clones. Introduction of the
      staphylococcal chromosome cassette mec (SCCmec) into virulent and epidemic
      isolates could pose serious threats to public health.

PMID- 17021113
TI  - Verification of the IDI-MRSA assay for detecting methicillin-resistant
      Staphylococcus aureus in diverse specimen types in a core clinical laboratory
      setting.
AB  - The IDI-MRSA assay has a sensitivity of 96% and a specificity of 96% when used to
      screen patients at extranasal sites. This verification study used previously
      unverified swabs and was undertaken in a core medical laboratory using
      nonmicrobiology technologists trained in sample processing, molecular laboratory
      work flow, and PCR practice.

PMID- 17021114
TI  - Comparative evaluation of three commercially available methodologies for
      hepatitis C virus genotyping.
AB  - We compared the performances of three hepatitis C virus genotyping methodologies
      supplied by Bayer, Abbott, and Third Wave Technologies. Genotypes were determined
      for 136 of 137 specimens by the Bayer method, 121 of 137 specimens by the Invader
      assay, and only 77 of 137 specimens by the Abbott assay. All reported genotypes
      were concordant by all three methods.

PMID- 17021115
TI  - Acquisition of Helicobacter pylori infection in rhesus macaques is most
      consistent with oral-oral transmission.
AB  - Socially housed rhesus monkeys rapidly acquired Helicobacter pylori infection,
      although the organism was rarely cultivated from saliva, feces, or the
      environment. Since the concentrations of H. pylori in vomit were compatible with
      what is known about the infectious dose, our results are most consistent with an
      oral-oral means of transmission.

PMID- 17021116
TI  - Comparison of PCR-based methods for typing Staphylococcus aureus isolates.
AB  - In this study, we compared the potentials of (i) a multiplex PCR-based multilocus
      variable-number tandem repeat (VNTR) assay; (ii) a triplex PCR coamplifying
      fragments of spa, coa, and the hypervariable region adjacent to the mecA gene;
      (iii) restriction profile analysis of the STAR repetitive element; (iv) randomly
      amplified polymorphic DNA analysis; (v) inter-IS256 PCR; and (vi) rep-MP3 PCR.
      Multilocus VNTR typing and triplex PCR (coa, spa, and hypervariable region)
      approaches showed excellent reproducibility and high discriminatory power;
      however, only multilocus VNTR typing could distinguish all pulsed-field gel
      electrophoresis and spa types. Multilocus VNTR typing appears to be the most
      useful PCR-based method for the rapid genotyping of Staphylococcus aureus
      strains.

PMID- 17021117
TI  - Molecular basis of resistance displayed by highly ciprofloxacin-resistant
      Salmonella enterica serovar Typhi in Bangladesh.
AB  - Highly ciprofloxacin-resistant (MIC, 512 microg/ml) strains of Salmonella
      enterica serovar Typhi were isolated from the blood of typhoid patients in Dhaka,
      Bangladesh. The strains were indistinguishable by their antibiograms, biotypes,
      and variable-number tandem repeat types and had matching point mutations at
      positions 83 and 87 of the gyrA gene. The isolation of these strains in an area
      of high endemicity indicates the need for continuous surveillance of antibiotic
      resistance of S. enterica serovar Typhi and for the rationalized use of
      ciprofloxacin.

PMID- 17021118
TI  - In vitro activities of daptomycin, ciprofloxacin, and other antimicrobial agents
      against the cells and spores of clinical isolates of Bacillus species.
AB  - Daptomycin inhibited 67 of 70 clinical isolates of Bacillus species at < or =1
      microg/ml and 100% of them at < or =2 microg/ml. It showed bactericidal activity
      similar to that of ciprofloxacin against vegetative cells but not against spores.
      For 2 strains, the ciprofloxacin MICs were >4 g/ml, and 10 strains were resistant
      to erythromycin.

PMID- 17021119
TI  - Evaluation of a multiplex PCR-based reverse line blot-hybridization assay for
      identification of serotype and surface protein antigens of Streptococcus
      agalactiae.
AB  - A 33-primer multiplex PCR-based reverse line blot (mPCR/RLB) assay was developed
      to identify Streptococcus agalactiae serotypes and surface protein antigen genes
      simultaneously. It was evaluated by using 551 clinical isolates. The mPCR/RLB
      assay was more sensitive than conventional serotyping, especially for protein
      antigen typing, but otherwise the results correlated well.

PMID- 17021120
TI  - Evaluation of molecular-Beacon, TaqMan, and fluorescence resonance energy
      transfer probes for detection of antibiotic resistance-conferring single
      nucleotide polymorphisms in mixed Mycobacterium tuberculosis DNA extracts.
AB  - The ability of fluorescence resonance energy transfer, molecular-beacon, and
      TaqMan probes to detect single nucleotide polymorphism (SNP) in the presence of a
      wild-type allele was evaluated using drug resistance-conferring SNPs in mixed
      Mycobacterium tuberculosis DNA. It was found that both the absolute quantity and
      the ratio of alleles determine the detection sensitivity of the probe systems.

PMID- 17021121
TI  - Treatment failure of nosocomial pertussis infection in a very-low-birth-weight
      neonate.
AB  - We describe a case of nosocomial maternal transmission of Bordetella pertussis to
      a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This
      case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates
      and in parents with clinical signs of pertussis and suggests that standard
      treatment may not be appropriate for VLBW neonates.

PMID- 17021122
TI  - Disseminated gonococcal infection in an immunocompetent patient caused by an
      imported Neisseria gonorrhoeae multidrug-resistant strain.
AB  - We herein report the microbiological features of a Neisseria gonorrhoeae strain
      isolated from an immunocompetent patient with disseminated gonococcal infection
      (DGI). The strain expressed the IA/IB serovar; was resistant to penicillin,
      tetracycline, and ciprofloxacin; and had presumably been acquired in Southeast
      Asia. To date, this is the first case reported in our country of DGI due to an
      imported multidrug-resistant strain.

PMID- 17021123
TI  - Osteomyelitis of the ulna caused by Porphyromonas gingivalis.
AB  - A 41-year-old man was provided with a jacket crown after a root end resection of
      a molar. Four months later, cortical destruction of the ulnar diaphysis with
      swelling and pain appeared in his forearm. No microorganism could be grown from
      an intraoperative tissue specimen, but bacterial 16S rRNA genes were detected by
      broad-range PCR, revealing Porphyromonas gingivalis as the causative agent of
      osteomyelitis.

PMID- 17021124
TI  - Shiga toxin 2-producing Acinetobacter haemolyticus associated with a case of
      bloody diarrhea.
AB  - We report the first Shiga toxin 2-producing Acinetobacter haemolyticus strain
      that was isolated from the feces of a 3-month-old infant with bloody diarrhea.
      Usual enteropathogenic bacteria were not detected. This finding suggests that any
      Shiga toxin-producing microorganism capable of colonizing the human gut may have
      the potential to cause illness.

PMID- 17021125
TI  - First isolation of Clostridium amygdalinum from a patient with chronic osteitis.
AB  - We describe a case of osteitis caused by a new and unusual Clostridium species,
      Clostridium amygdalinum, an environmental, moderately thermophilic bacterium.
      This is the first documented report of human infection caused by this organism.

PMID- 17021126
TI  - False-positive results obtained by following a commonly used reverse
      transcription-PCR protocol for detection of influenza A virus.

PMID- 17021127
TI  - Retroviremia in commercial pigs and its preliminary association with poor health.

PMID- 17021128
TI  - When is "abnormal" abnormal? Dealing with the slightly out of range laboratory
      result.

PMID- 17021129
TI  - Coeliac disease: an update for pathologists.
AB  - Coeliac disease is the manifestation of an immune hypersensitivity reaction
      towards gluten and related proteins, in genetically predisposed people. Although
      the precise pathogenesis of this condition remains to be fully elucidated, it is
      probably multifactorial in origin. The diagnosis of coeliac disease has
      traditionally depended on intestinal biopsies alone; nowadays, the diagnosis has
      been expanded to include an array of serological markers. This review is intended
      to offer pathologists an update of the relevant history and immunopathology
      pertaining to coeliac disease and also to offer recommendations on the ongoing
      responsibilities of the pathologist in the diagnosis and reporting of coeliac
      disease.

PMID- 17021130
TI  - Diagnosis and grading of dysplasia in Barrett's oesophagus.
AB  - This review focuses on the pathological features of dysplasia in Barrett's
      oesophagus. Two categorisation schemes are used for grading dysplasia in the
      gastrointestinal tract, including Barrett's oesophagus. The inflammatory bowel
      disease dysplasia morphology study group system is the one most commonly used in
      the USA. However, some European and most far Eastern countries use the Vienna
      classification system, which uses the term "non-invasive neoplasia" instead of
      low-grade dysplasia (LGD) or high-grade dysplasia (HGD) and also uses the term
      "suspicious for invasive carcinoma" for lesions that show equivocal cytological
      or architectural features of tissue invasion. The degree of dysplasia is based on
      a combination of cytological and architectural atypia. However, the precise
      number of HGD crypts that is necessary to upgrade a biopsy from LGD to HGD has
      never been investigated and varies widely among expert gastrointestinal
      pathologists. The extent of dysplasia, particularly LGD, has also been recognised
      recently as an important prognostic parameter in Barrett's oesophagus. Other
      problematic areas of dysplasia interpretation include differentiation of
      regenerating epithelium versus LGD and separating HGD from carcinoma. Dysplasia
      associated with macroscopically visible lesions, such as ulcers, nodules or
      polyps, carry a high risk of synchronous or metachronous adenocarcinoma.
      Recently, immunostaining for alpha-methylacyl-CoA-racemase has been shown to have
      a high degree of specificity for detection of dysplasia in Barrett's oesophagus
      and may be used to help distinguish negative from positive biopsies in this
      condition. In this review, the problematic areas in dysplasia interpretation are
      outlined and a specific approach to these issues is discussed.

PMID- 17021131
TI  - Patched homologue 1 mutations in four Japanese families with basal cell nevus
      syndrome.
AB  - AIM: To search for patched homologue 1 (PTCH1) mutations in four families with
      basal cell nevus syndrome (BCNS). METHODS: Mutation analysis of PTCH1 in
      unrelated Japanese families affected with BCNS was carried out by direct
      sequencing. RESULTS: Six novel PTCH1 mutations, 833G-->A in exon 6, 1415C-->A and
      1451G-->T in exon 10, 2798delC in exon 17, 2918-2925dupAGTTCCCT in exon 18 and
      3956C-->A in exon 23, were identified. CONCLUSIONS: Among the six PTCH1
      mutations, two frameshift mutations (2798delC and 2918-2925dupAGTTCCCT) and one
      nonsense mutation (833G-->A) are predicted to lead to premature termination of
      PTCH1 protein translation. Three simultaneous mutations, 1415C-->A (A472D) and
      1451G-->T (G484V) in exon 10, and 3956G-->A (R1319H) in exon 23, were found on
      one allele in only affected members in one family and none of them were found
      among 90 unrelated healthy Japanese. The three mutations on one chromosome may
      have resulted from errors in the recombinational repair process and this is the
      first report on the PTCH1 mutations due to such a mechanism.

PMID- 17021132
TI  - Pancreatic polypeptide cell hyperplasia of the pancreas.
AB  - A case of pancreatic polypeptide cell hyperplasia in a 76-year-old man who
      presented with subacute bowel pseudo-obstruction is reported. A computed
      tomography scan incidentally showed a pancreatic head lesion that was resected by
      pancreaticoduodenectomy. Histological examination showed expansion of the
      endocrine pancreas with increased numbers of pancreatic polypeptide cells in
      irregularly enlarged islets, ragged endocrine cell clusters, ductulo-insular
      complexes and microadenomas. The clinicopathological features of this rare and
      poorly understood condition are discussed.

PMID- 17021133
TI  - Peritoneal mucinous cystadenocarcinoma of probable urachal origin: a challenging
      diagnosis.
AB  - This report describes the case of a mucinous cystadenocarcinoma of probable
      urachal origin that presented with mass effect, precipitating deep venous
      thrombosis and pulmonary embolism. The patient presented with acute symptoms of
      leg swelling, pain and dyspnoea, and a vague awareness of lower abdominal
      distension. Computer tomography showed a cystic mass closely related to the
      anterior abdominal wall and the superior aspect of the bladder. A 1500 cm(3) cyst
      adherent to the dome of the urinary bladder was resected on laparotomy. Partial
      cystectomy was not carried out in the belief that the cyst represented a benign
      lesion. Subsequent imaging has shown cystic changes in the anterior bladder wall,
      and the patient has been referred for partial cystectomy.

PMID- 17021134
TI  - Worrisome histologic alterations following fine-needle aspiration of the
      parathyroid.
AB  - Fine-needle aspiration (FNA) is a procedure that is increasingly being performed.
      Artefacts occurring after FNA are reported to complicate the histological
      analysis of the tissue, mainly in the thyroid; WHAFFT (worrisome histologic
      alterations following FNA of thyroid) is well documented in the literature. The
      case of a male patient with hypercalcaemia who was subsequently found to have a
      nodule in the thyroid gland is reported here. He underwent FNA, followed by a
      total thyroidectomy and parathyroidectomy. The abnormality in the parathyroid
      gland showed worrisome histological changes that were suspicious of a malignant
      lesion, resembling the changes seen in the thyroid gland after FNA. Parathyroid
      cells were identified by a review of the previous FNA. The concept of WHAFFT,
      which can mimic the features of malignancy in the parathyroid gland, is therefore
      introduced.

PMID- 17021135
TI  - A new case of Carney triad: gastrointestinal stromal tumours and leiomyoma of the
      oesophagus do not show activating mutations of KIT and platelet-derived growth
      factor receptor alpha.
AB  - The Carney triad is a rare syndrome of unknown aetiology, with synchronous or
      metachronous appearance of rare neoplasms: gastrointestinal stromal tumours
      (GISTs), pulmonary chondromas and extra-adrenal paragangliomas. In most cases,
      the Carney triad is incomplete. The combination encountered typically, GISTs and
      pulmonary chondromas, was also seen in our patient, a 22-year-old woman. She was
      diagnosed with the triad after Billroth II gastrectomy for histologically proved
      gastric GISTs. The diagnosis of pulmonary chondromas was confirmed by
      transthoracic, computed tomography-guided needle biopsy. An oesophageal leiomyoma
      was resected 2 years after the initial diagnosis, on suspicion of paraganglioma.
      The clinical course of the patient has been uneventful since. The last follow-up
      was carried out 6 years after the initial diagnosis. On histological examination,
      the cells of gastric GIST were partly positive for CD34, whereas CD117 was
      expressed in all areas in variable intensity and S-100 protein was negative. The
      oesophageal tumour was classified as leiomyoma due to strong immunopositivity for
      smooth muscle actin and desmin, being negative for CD34 and CD117. Two different
      gastric GIST lesions as well as the oesophageal leiomyoma and normal tissue were
      analysed for activating mutations in common hot spots of KIT (exon 9 and 11) and
      platelet-derived growth factor receptor alpha (exon 18), but in all probes wild
      type sequences were found. These results are in accordance with the first
      published analyses of GIST lesions from Carney patients.

PMID- 17021136
TI  - Symptomatic colonic spirochaetosis in an immunocompetent patient.
AB  - Spirochaetes are organisms that can infect the colon of people with normal or
      compromised immune systems. Infected patients can present with a variety of
      gastrointestinal symptoms, including diarrhoea and rectal bleeding. However, some
      report a lack of association between specific symptoms and the presence of
      spirochaetes. It is therefore unclear whether the spirochaetes colonising the
      colon are true pathogens. Diagnosis is typically made by histological
      examination, with the biopsy specimen showing a band-like growth of spirochaetes
      adherent to the colonic luminal surface, giving an accentuated brush-border
      appearance. A course of metronidazole can eliminate the spirochaetes, but
      treatment might not lead to improvement of symptoms. Owing to the lack of a
      definite association between symptoms and the presence of spirochaetes,
      observation without specific antibiotic treatment can be pursued in most
      patients.

PMID- 17021137
TI  - e19a2 BCR-ABL fusion transcript in typical chronic myeloid leukaemia: a report of
      two cases.
AB  - This report describes two patients with chronic myeloid leukaemia (CML): one of
      them developed accelerated phase CML and died 8 years after diagnosis and the
      other is at the chronic phase. Sequence analysis of reverse transcription
      polymerase chain reaction products showed the presence of BCR-ABL fusion
      transcript e19a2. This finding suggests that CML carrying mu-BCR breakpoint may
      exhibit a clinical course similar to typical CML.

PMID- 17021139
TI  - Coexpression of an unusual form of the EWS-WT1 fusion transcript and interleukin
      2/15 receptor betamRNA in a desmoplastic small round cell tumour.
AB  - BACKGROUND: The beta chain of the interleukin 2/15 receptor (IL-2/15Rbeta) is
      induced by the expression of the EWS-WT1. A case of desmoplastic small round cell
      tumour (DSRCT) expressing only an unusual EWS-WT1 treated by us is reported here.
      AIM: To characterise an unusual form of EWS-WT1. METHODS: Frozen tissue sections
      of the axillary tumour were examined using a laser-assisted microdissection
      technique and reverse transcriptase polymerase chain reaction. RESULTS: The novel
      fusion of exon 8 of EWS and the defective exon 10 of WT1 (-KTS) was detected.
      Although it was an unusual form, the coexpression of the present EWS-WT1, IL
      2/15Rbeta and Janus kinase (JAK1) mRNA was detected in the tumour cells. IL-2 and
      signal transducers and activators of transcription (STAT5) mRNA were detected in
      both tumour and stromal cells. CONCLUSION: The induction of the IL-2/15 receptor
      signalling pathway may contribute to tumorigenesis in DSRCT through a paracrine
      or an autocrine system, even though the EWS-WT1 was an unusual form.

PMID- 17021138
TI  - Expression of calcitonin receptor-like receptor in human vascular tumours.
AB  - BACKGROUND: Vascular tumours such as Kaposi's sarcoma and capillary haemangioma
      are characterised by abnormal vascularisation and proliferation of endothelial
      cells or neoplastic cells. Adrenomedullin, a potent vasodilative peptide, and its
      receptor, calcitonin receptor-like receptor (CRLR), play an important part in
      angiogenesis. AIM: To establish whether this system also plays a part in vascular
      diseases, showing abnormal proliferation such as vascular tumours. METHODS: CRLR
      expression was investigated in several specimens of Kaposi's sarcoma and other
      vascular tumours, using immunohistochemical analysis with a previously described
      CRLR-specific polyclonal antibody and reverse transcriptase-polymerase chain
      reaction. RESULTS: Intense and specific CRLR-immunoreactive staining of
      neoplastic cells was observed in all specimens, which was of greater intensity
      than similar staining of adjacent normal endothelium. CONCLUSIONS: CRLR is
      expressed in vascular tumours and, with adrenomedullin, may have a role in
      neoplastic vascular growth.

PMID- 17021140
TI  - Splitting bone marrow trephines into frozen and fixed fragments allows parallel
      histological and molecular detection of B cell malignant infiltrates.
AB  - Clonality analysis of the immunoglobulin heavy chain (IgH) gene is helpful in
      identifying malignant B cell infiltrates in the bone marrow and is usually
      carried out on separate aspirates or on the same formalin-fixed decalcified bone
      marrow specimen. To determine whether the removal of the decalcification step
      would improve the molecular analysis, we first studied 12 bone marrow specimens
      with lymphoma infiltration split into a fixed and a small frozen fragment. Both
      the detection rate of IgH gene monoclonality and DNA quality were found to be
      superior in the frozen part than in the fixed part. Conversely, to evaluate
      whether the split would compromise histological analysis, we selected a series of
      134 bone marrow specimens obtained from patients with small B cell lymphoma and
      showing IgH monoclonality on the frozen part. The histological detection rate of
      infiltrated or suspicious infiltrates (95%) on the fixed part was not altered by
      saving a frozen part.

PMID- 17021141
TI  - Simplified detection of microsatellite instability in colorectal cancer without
      the need for corresponding germline DNA analysis.
AB  - A panel of five quasimonomorphic mononucleotide repeats that dispenses with the
      need to analyse corresponding germline DNA was proposed by Suraweera et al for
      the detection of high-frequency microsatellite instability (MSI) in colorectal
      cancer. Using this panel, a simplified and a more sensitive (compared with the
      original) algorithm (p<0.05) was developed to define the instability of each
      repeat by assessing the morphological shape of its plot and not its absolute
      length. 103 cases of colorectal tumours were investigated and the results
      compared with those obtained by the analysis of five consensus microsatellites
      (Bethesda reference panel). By the proposed method, a higher specificity, but no
      loss of sensitivity, was found. Thus, the use of the five mononucleotide repeats
      in combination with the modified assessment technique simplifies the assessment
      of MSI, while retaining the sensitivity of the Bethesda panel for the detection
      of high-frequency MSI.

PMID- 17021142
TI  - Writing the methods.

PMID- 17021143
TI  - Clinical habits and the psychiatrist: an adult developmental model focusing on
      the academic psychiatrist.
AB  - OBJECTIVE: The authors examine the development of the psychiatrist from an adult
      developmental perspective, focusing on the early development and consolidation of
      highly adaptive clinical and other professional habits. They place special
      emphasis on the professional development of the academic psychiatrist. METHOD:
      The authors review and use literature on adult psychological development as a
      formative template upon which a prototypical psychiatrist proceeds through a
      telescoping series of adult developmental stages. At each stage of clinical
      development, specific tasks are identified and outlined, and articles from the
      academic psychiatry literature are cited to provide content-specific examples of
      the development of academic and clinical habits of importance to those
      psychiatrists who then develop an academic career. RESULTS: The clinical
      development of the psychiatrist follows either a continuous or episodic process
      that parallels the broader themes of adult development, allowing for optimal
      integration of the interests and skills of the individual in a niche within the
      increasingly diverse field of psychiatry. For the academic psychiatrist, a
      continuation of this model applies to development as a clinical instructor and
      researcher. CONCLUSIONS: Optimum developmental attention to clinical habits and
      skills begins in medical school and proceeds sequentially throughout subsequent
      career stages, correlating with subsequent stages of adult development. The
      authors describe in functional terms strategies for successful navigation of
      these challenges in clinical habits development. At all stages, mentorship and
      supervision are highly encouraged, as is attention to macrolevel changes in the
      clinical and administrative milieu.

PMID- 17021144
TI  - Training in tobacco treatments in psychiatry: a national survey of psychiatry
      residency training directors.
AB  - OBJECTIVE: Nicotine dependence is the most prevalent substance abuse disorder
      among adult psychiatric patients and is a leading cause of death and disability.
      This study examines training in tobacco treatment in psychiatry residency
      programs across the United States. METHOD: The authors recruited training
      directors to complete a survey of their program's curriculum related to tobacco
      treatment, attitudes related to treating tobacco in psychiatry, and perceptions
      of residents' skills for addressing nicotine dependence in psychiatric patients.
      RESULTS: Respondents were representative of the national pool. Half of the
      programs provided training in tobacco treatments for a median duration of 1 hour.
      Content areas covered varied greatly. Programs with tobacco-related training
      expressed more favorable attitudes toward addressing tobacco in psychiatry and
      were more likely to report confidence in their residents' skills for treating
      nicotine dependence. Programs without tobacco training reported a lack of faculty
      expertise on tobacco treatments. Most training directors reported moderate to
      high interest in evaluating a model tobacco curriculum for psychiatry and stated
      they would dedicate an average of 4 hours of curriculum time. CONCLUSIONS: The
      findings demonstrate the need for and interest in a model tobacco treatment
      curriculum for psychiatry residency training. Training psychiatrists offers the
      potential of delivering treatment to one of the largest remaining groups of
      smokers: patients with mental disorders.

PMID- 17021145
TI  - Overcoming barriers in working with families.
AB  - OBJECTIVE: The Accreditation Council for Graduate Medical Education and the
      Residency Review Committee for psychiatry outline the expected competencies for
      residents. These competencies include working with families. This article
      describes barriers that residents face when working with families, and offers
      ways to overcome these barriers. METHOD: In 23 years of combined experience
      teaching family therapy to psychiatry residents, the authors have identified
      typical barriers that residents face when beginning to work with families.
      RESULTS: Six clinical vignettes, with the resident's concerns, the supervisor's
      intervention and the resident's response, illustrate these barriers. CONCLUSIONS:
      In order for residents to become skilled in working with families, barriers
      should be made explicit and ways of overcoming these barriers should be discussed
      clearly with residents.

PMID- 17021146
TI  - Implementing interpersonal psychotherapy in a psychiatry residency training
      program.
AB  - OBJECTIVE: Interpersonal psychotherapy (IPT) for depression is a brief, well
      researched treatment for acute major depression. This article describes the
      implementation of IPT as an evidence-based treatment for depression in a
      psychiatry residency program. METHOD: The authors tracked the implementation
      process over 5 years as interpersonal psychotherapy was systematically
      incorporated into residency training. RESULTS: The authors outline key
      ingredients for and challenges to effecting change. CONCLUSIONS: Implementation
      of interpersonal psychotherapy in psychiatry residency training was a cornerstone
      for learning evidence-based treatment approaches as well as for conveying core
      psychotherapy concepts.

PMID- 17021148
TI  - Determining, monitoring, and verifying patient-student involvement (ED-2) in a
      psychiatry clerkship: preliminary findings.
AB  - OBJECTIVE: This article describes the process and preliminary findings that a
      department of psychiatry developed to meet a new Liaison Committee on Medical
      Education (LCME) educational standard known as ED-2. METHOD: At an educational
      retreat, 92% of faculty and 56% of residents who attended developed the types of
      patient symptoms all students should see and document during a 6-week psychiatry
      rotation. Data from the first three rotations were collected, including the
      opinions of faculty and students. RESULTS: Both faculty and students found the
      system easy to use. Almost half (46%) of the encounters were met through
      observation with a range of 12% to 81%. There was a significant inverse
      correlation between students who met encounters through observation and Shelf
      examination scores. DISCUSSION: The Required Patient Encounter card tracks the
      patients whom students are seeing, thus enabling the clerkship to meet new LCME
      educational standards. Future directions will include evaluating whether the
      categories of symptoms need revision and whether there should be a maximum number
      of encounters that can be met through observation.

PMID- 17021147
TI  - Gender bias in the diagnosis of a geriatric standardized patient: a potential
      confounding variable.
AB  - BACKGROUND: Gender bias has been reported in the diagnosis and treatment of
      patients with a variety of illnesses. In the context of our 10-station fourth
      year Objective Structured Clinical Evaluation, we queried whether this could
      influence diagnosis in a geriatric case. Case writers hypothesized that, due to
      this bias, the female standardized patient may be diagnosed with depression more
      often than the male. METHOD: A male or female geriatric standardized patient
      protrayed a dysphoric widow with mild cognitive impairment. Students examined the
      patient and documented the clinical encounter and their differential diagnosis.
      RESULTS: Major depression was diagnosed in 93/107 female standardized patient
      encounters compared with 58/78 male exams, with the female students contributing
      most to this difference. DISCUSSION: The potential for gender bias in medical
      care and in education remains a concern. We need to be mindful of this when
      designing clinical skills assessments.

PMID- 17021149
TI  - Formal training in women's issues in psychiatry: a survey of psychiatry residency
      training directors.
AB  - OBJECTIVE: The authors describe the availability of formal residency training
      opportunities in women's issues in psychiatry and explore the potential
      relationships between the availability of training and characteristics of
      residency programs. METHOD: The authors surveyed psychiatry residency training
      directors to identify program characteristics and training opportunities.
      RESULTS: Certain didactic subjects were available in greater than 80% of
      residencies. Clinical training opportunities were less available and often not
      required. CONCLUSIONS: Selected didactic training in gender issues is commonly
      available in a majority of residencies. Nevertheless, general clinical
      instruction and didactic instruction in several important topics are less
      available.

PMID- 17021151
TI  - Consultation-liaison psychiatrists on bioethics committees: opportunities for
      academic leadership.
AB  - OBJECTIVE: This article briefly reviews the history of the relationship between
      psychiatry and the leadership of ethics committees as a background for examining
      appropriate educational initiatives to adequately prepare residents and early
      career psychiatrists to serve as leaders of ethics committees. METHOD: A Medline
      review of literature on psychiatry and ethics committees and consultation as well
      as recent survey data from the Academy of Psychosomatic Medicine indicate that
      psychosomatic medicine psychiatrists are particularly qualified and interested in
      serving as chairs of ethics committees. The authors compare knowledge and skills
      obtained in psychiatric training with the Society for Heath and Human Values and
      the Society for Bioethics Consultation Task Force on standards for ethics
      consultation proposed as core competencies for ethics committee leadership.
      RESULTS: Psychiatric residency and fellowship training in psychosomatic medicine
      can provide the knowledge and skill sets to meet the standards for ethics
      consultation. Further professional development through pursuit of formal ethics
      training, advance degrees in bioethics, mentoring, and residency and felloships
      focus on ethics and enhance competency, confidence, and the skills required for
      ethics committee leadership. CONCLUSIONS: Academic psychiatrists, particularly
      those in psychosomatic medicine, have historically made a significant
      contribution as chairs of ethics committees. Continuation and expansion of this
      leadership may require interested psychiatrists to obtain additional training in
      bioethics.

PMID- 17021150
TI  - A neural systems-based neurobiology and neuropsychiatry course: integrating
      biology, psychodynamics, and psychology in the psychiatric curriculum.
AB  - OBJECTIVE: Psychotherapy and biological psychiatry remain divided in psychiatry
      residency curricula. Behavioral neurobiology and neuropsychiatry provide a
      systems-level framework that allows teachers to integrate biology,
      psychodynamics, and psychology. METHOD: The authors detail the underlying
      assumptions and outline of a neural systems-based neuroscience course they teach
      at the National Capital Consortium Psychiatry Residency Program. They review
      course assessment reports and classroom observations. RESULTS: Self-report
      measures and teacher observations are encouraging. By the end of the course,
      residents are able to discuss both neurobiological and
      psychodynamic/psychological concepts of distributed biological neural networks.
      They verbalize an understanding that psychology is biology, that any distinction
      is artificial, and that both are valuable. CONCLUSIONS: A neuroscience curriculum
      founded on the underlying principles of behavioral neurobiology and
      neuropsychiatry is inherently anti-reductionistic and facilitates the acquisition
      of detailed information as well as critical thinking and cross-disciplinary
      correlations with psychological theories and psychotherapy.

PMID- 17021152
TI  - Through the golden chalkboard: twelve teaching pearls on the teaching-learning
      process in psychiatry.

PMID- 17021153
TI  - A concise conceptualization of formulation.

PMID- 17021155
TI  - Napoleon Dynamite: Asperger's disorder or Geek NOS?
AB  - Napoleon Dynamite, the quirky hit film from 2004, is a fascinating portrayal of a
      teenager with social difficulties. The character Napoleon provokes intriguing
      diagnostic questions in distinguishing between mental illness and the spectrum of
      normal behavior. He demonstrates several symptoms of Asperger's disorder, yet he
      also challenges the notion that children and adolescents with Asperger's spectrum
      disorders will not be accepted or understood. He forms genuine, connected
      friendships, and fans of the movie appear to celebrate his quirkiness rather than
      ridicule his oddities. The authors explore the extent to which cultural issues
      have an impact on psychiatric phenomenology, as well as the potential treatment
      issues for someone with his apparent social challenges. Finally, the authors
      offer possible explanations for Napoleon's immense popularity, especially among
      adolescents. With the rise of computer technology, our culture has fully embraced
      the idea of what has come to be called "geekdom," and the authors consider the
      idea that Napoleon's popularity may be a more rural equivalent for this
      phenomenon. The success of the movie appears to be related to a genuine
      celebration of Napoleon himself.

PMID- 17021156
TI  - P2BAT: a massive parallel implementation of PBAT for genome-wide association
      studies in R.
AB  - The software tool P2BAT provides a massive parallel and user friendly
      implementation of the PBAT-analysis tools for family-based association tests
      (FBATs) in large-scale studies, including genome-wide association studies with
      several thousand subjects. Built on the original PBAT-implementation of the Lange
      Van Steen algorithm to bypass the multiple testing problem in family-based
      association studies, P2BAT integrates all PBAT-analysis tools for binary and
      complex traits into R and makes them accessible through a user-friendly GUI. The
      genome-wide analysis tools are fully automated and can be ran massively parallel
      directly through the GUI. P2BAT is fully documented and contains graphical output
      tools for time-to-onset analysis. P2BAT also features the ability to test for
      gene and environment/drug interaction. AVAILABILITY: The P2BAT package is
      available as the R package 'pbatR' which can be downloaded from http://cran.r
      project.org/. The PBAT-software is available at
      http://www.biostat.harvard.edu/~clange/.

PMID- 17021157
TI  - Analysis of HIV-1 pol sequences using Bayesian Networks: implications for drug
      resistance.
AB  - Human Immunodeficiency Virus-1 (HIV-1) antiviral resistance is a major cause of
      antiviral therapy failure and compromises future treatment options. As a
      consequence, resistance testing is the standard of care. Because of the high
      degree of HIV-1 natural variation and complex interactions, the role of
      resistance mutations is in many cases insufficiently understood. We applied a
      probabilistic model, Bayesian networks, to analyze direct influences between
      protein residues and exposure to treatment in clinical HIV-1 protease sequences
      from diverse subtypes. We can determine the specific role of many resistance
      mutations against the protease inhibitor nelfinavir, and determine relationships
      between resistance mutations and polymorphisms. We can show for example that in
      addition to the well-known major mutations 90M and 30N for nelfinavir resistance,
      88S should not be treated as 88D but instead considered as a major mutation and
      explain the subtype-dependent prevalence of the 30N resistance pathway.

PMID- 17021158
TI  - TimeTree: a public knowledge-base of divergence times among organisms.
AB  - Biologists and other scientists routinely need to know times of divergence
      between species and to construct phylogenies calibrated to time (timetrees).
      Published studies reporting time estimates from molecular data have been
      increasing rapidly, but the data have been largely inaccessible to the greater
      community of scientists because of their complexity. TimeTree brings these data
      together in a consistent format and uses a hierarchical structure, corresponding
      to the tree of life, to maximize their utility. Results are presented and
      summarized, allowing users to quickly determine the range and robustness of time
      estimates and the degree of consensus from the published literature.
      AVAILABILITY: TimeTree is available at http://www.timetree.net

PMID- 17021159
TI  - CREMOFAC--a database of chromatin remodeling factors.
AB  - MOTIVATION: Chromatin-remodeling is an important event in the eukaryotic nucleus
      rendering nucleosomal DNA accessible for various transaction processes.
      Remodeling Factors facilitate the dynamic nature of chromatin through
      participation of the collective action of (i) ATP and (ii) Non-ATP dependent
      factors. Considering the importance of these factors in eukaryotes, we have
      developed, CREMOFAC, a dedicated and frequently updated web-database for
      chromatin-remodeling factors. RESULTS: The database harbors factors from 49
      different organisms reported in literature and facilitates a comprehensive search
      for them. In addition, it also provides in-depth information for the factors
      reported in the three widely studied mammals namely, human, mouse and rat.
      Further, information on literature, pathways and phylogenetic relationships has
      also been covered. The development of CREMOFAC as a central repository for
      chromatin-remodeling factors and the absence of such a pre-existing database
      heighten its utility thus making its presence indispensable. AVAILABILITY:
      http://www.jncasr.ac.in/cremofac/

PMID- 17021160
TI  - The tYNA platform for comparative interactomics: a web tool for managing,
      comparing and mining multiple networks.
AB  - Biological processes involve complex networks of interactions between molecules.
      Various large-scale experiments and curation efforts have led to preliminary
      versions of complete cellular networks for a number of organisms. To grapple with
      these networks, we developed TopNet-like Yale Network Analyzer (tYNA), a Web
      system for managing, comparing and mining multiple networks, both directed and
      undirected. tYNA efficiently implements methods that have proven useful in
      network analysis, including identifying defective cliques, finding small network
      motifs (such as feed-forward loops), calculating global statistics (such as the
      clustering coefficient and eccentricity), and identifying hubs and bottlenecks.
      It also allows one to manage a large number of private and public networks using
      a flexible tagging system, to filter them based on a variety of criteria, and to
      visualize them through an interactive graphical interface. A number of commonly
      used biological datasets have been pre-loaded into tYNA, standardized and grouped
      into different categories. AVAILABILITY: The tYNA system can be accessed at
      http://networks.gersteinlab.org/tyna. The source code, JavaDoc API and WSDL can
      also be downloaded from the website. tYNA can also be accessed from the Cytoscape
      software using a plugin.

PMID- 17021161
TI  - FoldUnfold: web server for the prediction of disordered regions in protein chain.
AB  - Identification of disordered regions in polypeptide chains is very important
      because such regions are essential for protein function. A new parameter, namely
      mean packing density of residues has been introduced to detect disordered regions
      in a protein sequence. We have demonstrated that regions with weak expected
      packing density would be responsible for the appearance of disordered regions.
      Our method (FoldUnfold) has been tested on datasets of globular proteins (559
      proteins) and long disordered protein segments (129 proteins) and showed improved
      performance over some other widely used methods, such as DISOPRED, PONDR VL3H,
      IUPred and GlobPlot. AVAILABILITY: The FoldUnfold server is available for users
      at http://skuld.protres.ru/~mlobanov/ogu/ogu.cgi. There is a link to our server
      through the web site of DisProt (http://www.disprot.org/predictors.php).

PMID- 17021162
TI  - Predicted function of the vaccinia virus G5R protein.
AB  - MOTIVATION: Of the approximately 200 proteins that have been identified for the
      vaccinia virus (VACV) genome, many are currently listed as having an unknown
      function, and seven of these are also found in all other poxvirus genomes that
      have been sequenced. The G5R protein of VACV is included in this list, and to
      date, very little is known about this essential and highly conserved protein.
      Conventional similarity searches of protein databases do not identify
      significantly similar proteins, and experimental approaches have been
      unsuccessful at determining protein function. RESULTS: Using HHsearch, a hidden
      Markov model (HMM) comparison search tool, the G5R protein was found to be
      similar to both human and archaeal flap endonucleases (FEN-1) with 96%
      probability. The G5R protein structure was subsequently successfully modeled
      using the Robetta protein structure prediction server with an archaeal FEN-1 as
      the template. The G5R model was then compared to the human FEN-1 crystal
      structure and was found to be structurally similar to human FEN-1 in both active
      site residues and DNA substrate binding regions.

PMID- 17021163
TI  - Open access and the future of the scientific research article.

PMID- 17021164
TI  - Starvation induces cAMP response element-binding protein-dependent gene
      expression through octopamine-Gq signaling in Caenorhabditis elegans.
AB  - The nervous system plays a critical role in adaptation to a new environment. In
      Caenorhabditis elegans, reduced access to food requires both changes in behavior
      as well as metabolic adaptation for survival, which is postulated to involve the
      bioamine octopamine. The transcription factor cAMP response element-binding
      protein (CREB) is generally activated by G-protein-coupled receptors (GPCRs) that
      activate G alpha(s) and is known to play an important role in long-term changes,
      including synaptic plasticity. We show that, in C. elegans, the CREB ortholog CRH
      1 (CREB homolog family member 1) activates in vivo a cAMP response element-green
      fluorescent protein fusion reporter in a subset of neurons during starvation.
      This starvation response is mediated by octopamine via the GPCR SER-3
      (serotonin/octopamine receptor family member 3) and is fully dependent on the
      subsequent activation of the G alpha(q) ortholog EGL-30 (egg-laying defective
      family member 30). The signaling cascade is only partially dependent on the
      phospholipase C beta (EGL-8) and is negatively regulated by G alpha(o) [GOA-1 (G
      protein, O, alpha subunit family member 1)] and calcium/calmodulin-dependent
      kinase [UNC-43 (uncoordinated family member 43)]. Nonstarved animals in a liquid
      environment mediate a similar response that is octopamine independent. The
      results show that the endogenous octopamine system in C. elegans is activated by
      starvation and that different environmental stimuli can activate CREB through G
      alpha(q).

PMID- 17021165
TI  - Preparatory delay activity in the monkey parietal reach region predicts reach
      reaction times.
AB  - To acquire something that we see, visual spatial information must ultimately
      result in the activation of the appropriate set of muscles. This sensory to motor
      transformation requires an interaction between information coding target location
      and information coding which effector will be moved. Activity in the monkey
      parietal reach region (PRR) reflects both spatial information and the effector
      (arm or eye) that will be used in an upcoming reach or saccade task. To further
      elucidate the functional role of PRR in visually guided movement tasks and to
      obtain evidence that PRR signals are used to drive arm movements, we tested the
      hypothesis that increased neuronal activity during a preparatory delay period
      would lead to faster reach reaction times but would not be correlated with
      saccade reaction times. This proved to be the case only when the type of movement
      and not the spatial goal of that movement was known in advance. The correlation
      was strongest in cells that showed significantly more activity on arm reach
      compared with saccade trials. No significant correlations were found during delay
      periods in which spatial information was provided in advance. These data support
      the idea that PRR constitutes a bottleneck in the processing of spatial
      information for an upcoming arm reach. The lack of a correlation with saccadic
      reaction time also supports the idea that PRR processing is effector specific,
      that is, it is involved in specifying targets for arm movements but not targets
      for eye movements.

PMID- 17021166
TI  - Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing
      benign familial neonatal-infantile seizures.
AB  - Mutations of voltage-gated Na+ channels are the most common cause of familial
      epilepsy. Benign familial neonatal-infantile seizures (BFNIS) is an epileptic
      trait of the early infancy, and it is the only well characterized epileptic
      syndrome caused exclusively by mutations of Na(V)1.2 Na+ channels, but no
      functional studies of BFNIS mutations have been done. The comparative study of
      the functional effects and the elucidation of the pathogenic mechanisms of
      epileptogenic mutations is essential for designing targeted and effective
      therapies. However, the functional properties of Na+ channels and the effects of
      their mutations are very sensitive to the cell background and thus to the
      expression system used. We investigated the functional effects of four of the six
      BFNIS mutations identified (L1330F, L1563V, R223Q, and R1319Q) using as
      expression system transfected pyramidal and bipolar neocortical neurons in short
      primary cultures, which have small endogenous Na+ current and thus permit the
      selective study of transfected channels. The mutation L1330F caused a positive
      shift of the inactivation curve, and the mutation L1563V caused a negative shift
      of the activation curve, effects that are consistent with neuronal
      hyperexcitability. The mutations R223Q and R1319Q mainly caused positive shifts
      of both activation and inactivation curves, effects that cannot be directly
      associated with a specific modification of excitability. Using physiological
      stimuli in voltage-clamp experiments, we showed that these mutations increase
      both subthreshold and action Na+ currents, consistently with hyperexcitability.
      Thus, the pathogenic mechanism of BFNIS mutations is neuronal hyperexcitability
      caused by increased Na+ current.

PMID- 17021167
TI  - Cdc42 and Rac1 signaling are both required for and act synergistically in the
      correct formation of myelin sheaths in the CNS.
AB  - The formation of myelin sheaths in the CNS is the result of a complex series of
      events involving oligodendrocyte progenitor cell (OPC) proliferation, directed
      migration, and the morphological changes associated with axon ensheathment and
      myelination. To examine the role of Rho GTPases in oligodendrocyte biology, we
      have used a conditional tissue-specific gene-targeting approach. Ablation of
      Cdc42 in cells of the oligodendrocyte lineage did not affect OPC proliferation,
      directed migration, or in vitro differentiation, but it led to the formation of a
      unique and stage-specific myelination phenotype. This was characterized by the
      extraordinary enlargement of the inner tongue of the oligodendrocyte process and
      concomitant formation of a myelin outfolding as a result of abnormal accumulation
      of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal
      accumulation of cytoplasm in the inner tongue of the oligodendrocyte process, and
      we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage
      dependent way to regulate myelination.

PMID- 17021168
TI  - Individual differences in amygdala activity predict response speed during working
      memory.
AB  - The human amygdala has classically been viewed as a brain structure primarily
      related to emotions and dissociated from higher cognition. We report here
      findings suggesting that the human amygdala also has a role in supporting working
      memory (WM), a canonical higher cognitive function. In a first functional
      magnetic resonance imaging (fMRI) study (n = 53), individual differences in
      amygdala activity predicted behavioral performance in a 3-back WM task.
      Specifically, higher event-related amygdala amplitude predicted faster response
      time (RT; r = -0.64), with no loss of accuracy. This relationship was not
      contingent on mood state, task content, or personality variables. In a second
      fMRI study (n = 21), we replicated the key finding (r = -0.47) and further showed
      that the correlation between the amygdala and faster RT was specific to a high
      working memory load condition (3-back) compared with a low working memory load
      condition (1-back). These results support models of amygdala function that can
      account for its involvement not only in emotion but also higher cognition.

PMID- 17021169
TI  - Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in
      transgenic mice with five familial Alzheimer's disease mutations: potential
      factors in amyloid plaque formation.
AB  - Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1,
      PS2) increase production of beta-amyloid 42 (Abeta42) and cause familial
      Alzheimer's disease (FAD). Transgenic mice that express FAD mutant APP and PS1
      overproduce Abeta42 and exhibit amyloid plaque pathology similar to that found in
      AD, but most transgenic models develop plaques slowly. To accelerate plaque
      development and investigate the effects of very high cerebral Abeta42 levels, we
      generated APP/PS1 double transgenic mice that coexpress five FAD mutations (5XFAD
      mice) and additively increase Abeta42 production. 5XFAD mice generate Abeta42
      almost exclusively and rapidly accumulate massive cerebral Abeta42 levels.
      Amyloid deposition (and gliosis) begins at 2 months and reaches a very large
      burden, especially in subiculum and deep cortical layers. Intraneuronal Abeta42
      accumulates in 5XFAD brain starting at 1.5 months of age (before plaques form),
      is aggregated (as determined by thioflavin S staining), and occurs within neuron
      soma and neurites. Some amyloid deposits originate within morphologically
      abnormal neuron soma that contain intraneuronal Abeta. Synaptic markers
      synaptophysin, syntaxin, and postsynaptic density-95 decrease with age in 5XFAD
      brain, and large pyramidal neurons in cortical layer 5 and subiculum are lost. In
      addition, levels of the activation subunit of cyclin-dependent kinase 5, p25, are
      elevated significantly at 9 months in 5XFAD brain, although an upward trend is
      observed by 3 months of age, before significant neurodegeneration or neuron loss.
      Finally, 5XFAD mice have impaired memory in the Y-maze. Thus, 5XFAD mice rapidly
      recapitulate major features of AD amyloid pathology and may be useful models of
      intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation.

PMID- 17021170
TI  - Dynamic synchrony of firing in the monkey prefrontal cortex during working-memory
      tasks.
AB  - Synchronized firing among neurons in the working brain is inferred to reflect
      coding by cell assemblies, which dynamically change their sizes and functional
      connections to encode various information. It therefore follows that, if
      synchronized firing reflects cell-assembly coding, it should show dynamic changes
      that depend on the tasks and events being processed and on the distance between
      the neurons. By using unique spike-sorting and multi-neuronal recording methods,
      we investigated such dynamics of synchrony in the prefrontal cortex of monkeys
      while they were successively performing two tasks in which working memory for
      either stimulus duration or color was required. Forty-eight percent of 1405
      neuronal pairs showed firing synchrony during the performance of the tasks.
      Almost half of such neuronal pairs showed fixed synchrony and constantly fired
      together in both tasks. However, some neuronal pairs showed task-dependent
      synchrony that appeared in only one of the tasks. Moreover, the other neuronal
      pairs showed event-task-dependent synchrony that appeared during stimulus or
      retention periods in the tasks, but the periods showing synchrony varied between
      the tasks. Fixed synchrony and task-dependent synchrony were mostly observed
      among neighboring neurons and showed little variation of spike timings; the event
      task-dependent synchrony, in contrast, was more often detected among distant
      neurons with larger variation of spike timings than the other two types of
      synchrony. These results suggest that some closely neighboring neurons have
      dynamic and sharp synchrony to represent certain situations (tasks), whereas some
      distant neurons show more dynamic and unstable synchronous firing to represent
      quickly changing events being processed in working memory.

PMID- 17021171
TI  - Combining priors and noisy visual cues in a rapid pointing task.
AB  - Statistical decision theory suggests that choosing an ideal action requires
      taking several factors into account: (1) prior knowledge of the probability of
      various world states, (2) sensory information concerning the world state, (3) the
      probability of outcomes given a choice of action, and (4) the loss or gain
      associated with those outcomes. In previous work, we found that, in many
      circumstances, humans act like ideal decision makers in planning a reaching
      movement. They select a movement aim point that maximizes expected gain, thus
      taking into account outcome uncertainty (motor noise) and the consequences of
      their actions. Here, we ask whether humans can optimally combine prior knowledge
      and uncertain sensory information in planning a reach. Subjects rapidly pointed
      at unseen targets, indicated with dots drawn from a distribution centered on the
      invisible target location. Target location had a prior distribution, the form of
      which was known to the subject. We varied the number of dots and hence target
      spatial uncertainty. An analysis of the sources of uncertainty impacting
      performance in this task indicated that the optimal strategy was to aim between
      the mean of the prior (the screen center) and the mean stimulus location
      (centroid of the dot cloud). With increased target location uncertainty, the aim
      point should have moved closer to the prior. Subjects used near-optimal
      strategies, combining stimulus uncertainty and prior information appropriately.
      Observer behavior was well modeled as having three additional sources of
      inefficiency originating in the motor system, calculation of centroid location,
      and calculation of aim points.

PMID- 17021172
TI  - Activity-independent regulation of dendrite patterning by postsynaptic density
      protein PSD-95.
AB  - Dendritic morphology determines many aspects of neuronal function, including
      action potential propagation and information processing. However, the question
      remains as to how distinct neuronal dendrite branching patterns are established.
      Here, we report that postsynaptic density-95 (PSD-95), a protein involved in
      dendritic spine maturation and clustering of synaptic signaling proteins, plays a
      novel role in regulating dendrite outgrowth and branching, independent of its
      synaptic functions. In immature neurons, overexpression of PSD-95 decreases the
      proportion of primary dendrites that undergo additional branching, resulting in a
      marked reduction of secondary dendrite number. Conversely, knocking down PSD-95
      protein in immature neurons increases secondary dendrite number. The effect of
      PSD-95 is activity-independent and is antagonized by cypin, a nonsynaptic protein
      that regulates PSD-95 localization. Binding of cypin to PSD-95 correlates with
      formation of stable dendrite branches. Finally, overexpression of PSD-95 in COS-7
      cells disrupts microtubule organization, indicating that PSD-95 may modulate
      microtubules to regulate dendritic branching. Whereas many factors have been
      identified which regulate dendrite number, our findings provide direct evidence
      that proteins primarily involved in synaptic functions can also play
      developmental roles in shaping how a neuron patterns its dendrite branches.

PMID- 17021173
TI  - Impaired volume regulation is the mechanism of excitotoxic sensitization to
      complement.
AB  - Previous work demonstrated that a brief, sublethal excitotoxic insult strikingly
      increased the sensitivity of cortical neurons to the cytotoxic effects of the
      terminal pathway of complement, a process termed "excitotoxic sensitization."
      Here, we sought to elucidate the cellular mechanism of excitotoxic sensitization
      in embryonic rat cortical neurons in vitro. Excitotoxic sensitization did not
      increase membrane attack complex deposition on cortical neurons and produced only
      a small reduction of membrane attack complex removal, because of a selective
      decrease of endocytic elimination. Membrane attack complexes and other osmotic
      stressors, namely hypotonic stress and glutamate, induced transient swelling of
      cortical neurons, followed by return to normal volume despite persistence of the
      stressor, a homeostatic response termed regulatory volume decrease (RVD). A
      minimal excitotoxic insult impaired this homeostatic response and sensitized
      neurons to cytotoxic effects of diverse osmotic stressors. Structurally distinct
      membrane-impermeable osmolytes, dextran and polyethylene glycol, prevented
      excitotoxic sensitization to diverse osmotic stressors including membrane attack
      complexes. Paraquat, a reactive oxygen species generator, alone was sufficient to
      impair RVD, and MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride], a
      reactive oxygen species scavenger, prevented excitotoxin-mediated impairment of
      RVD. Together, these findings demonstrate that impairment of RVD is the mechanism
      of excitotoxic sensitization, that reactive oxygen species alone are sufficient
      to impair RVD, and that reactive oxygen species are necessary for excitotoxic
      sensitization-mediated impairment of RVD.

PMID- 17021175
TI  - Age-independent synaptogenesis by phosphoinositide 3 kinase.
AB  - Synapses are specialized communication points between neurons, and their number
      is a major determinant of cognitive abilities. These dynamic structures undergo
      developmental- and activity-dependent changes. During brain aging and certain
      diseases, synapses are gradually lost, causing mental decline. It is, thus,
      critical to identify the molecular mechanisms controlling synapse number. We show
      here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number
      in both Drosophila larval motor neurons and adult brain projection neurons. The
      supernumerary synapses induced by PI3K overexpression are functional and elicit
      changes in behavior. Remarkably, PI3K activation induces synaptogenesis in aged
      adult neurons as well. We demonstrate that persistent PI3K activity is necessary
      for synapse maintenance. We also report that PI3K controls the expression and
      localization of synaptic markers in human neuroblastoma cells, suggesting that
      PI3K synaptogenic activity is conserved in humans. Thus, we propose that PI3K
      stimulation can be applied to prevent or delay synapse loss in normal aging and
      in neurological disorders.

PMID- 17021174
TI  - The chloride intracellular channel protein CLIC5 is expressed at high levels in
      hair cell stereocilia and is essential for normal inner ear function.
AB  - Although CLIC5 is a member of the chloride intracellular channel protein family,
      its association with actin-based cytoskeletal structures suggests that it may
      play an important role in their assembly or maintenance. Mice homozygous for a
      new spontaneous recessive mutation of the Clic5 gene, named jitterbug (jbg),
      exhibit impaired hearing and vestibular dysfunction. The jbg mutation is a 97 bp
      intragenic deletion that causes skipping of exon 5, which creates a translational
      frame shift and premature stop codon. Western blot and immunohistochemistry
      results confirmed the predicted absence of CLIC5 protein in tissues of jbg/jbg
      mutant mice. Histological analysis of mutant inner ears revealed dysmorphic
      stereocilia and progressive hair cell degeneration. In wild-type mice, CLIC5
      specific immunofluorescence was detected in stereocilia of both cochlear and
      vestibular hair cells and also along the apical surface of Kolliker's organ
      during cochlear development. Refined immunolocalization in rat and chicken
      vestibular hair cells showed that CLIC5 is limited to the basal region of the
      hair bundle, similar to the known location of radixin. Radixin immunostaining
      appeared reduced in hair bundles of jbg mutant mice. By mass spectrometry and
      immunoblotting, CLIC5 was shown to be expressed at high levels in stereocilia of
      the chicken utricle, in an approximate 1:1 molar ratio with radixin. These
      results suggest that CLIC5 associates with radixin in hair cell stereocilia and
      may help form or stabilize connections between the plasma membrane and the
      filamentous actin core.

PMID- 17021176
TI  - Bidirectional trafficking of prostaglandin E2 receptors involved in long-term
      potentiation in visual cortex.
AB  - Although prostaglandin E2 (PGE2) has a broad spectrum of biological activities
      that have been confirmed by previous studies, the roles of PGE2 in synaptic
      plasticity such as long-term potentiation (LTP) in the CNS have yet to be
      characterized in detail. The present results of electrophysiological and
      biochemical studies indicated that PGE2 is actually produced in acute visual
      cortex slices in response to theta-burst stimulation (TBS) and is involved
      postsynaptically in TBS-induced LTP. RNA interference (RNAi) for PGE2 receptor
      subtypes EP2 and EP3, which are known to upregulate and downregulate the level of
      cAMP, respectively, induced significant decreases and increases of LTP,
      respectively. Moreover, analysis of the localization of receptor subtypes at the
      membrane surface or cytosol showed that stimuli such as TBS regulate the
      trafficking of EP2 and EP3 between the membrane and cytosol of the postsynapses,
      rising up to and leaving the membrane, respectively, resulting in increased and
      decreased expression of EP2 and EP3 at the membrane, respectively. Increased
      activation of EP2 and decreased activation of EP3 by PGE2 synergistically induce
      an increase in cAMP level, which may induce LTP. This causes activation of CREB
      (cAMP response element-binding protein) in the postsynaptic cells, which may be
      involved in the maintenance of LTP. These observations indicate that in TBS
      induced LTP of the visual cortex, PGE2 is released from the postsynaptic cells
      and then activates PGE2 receptors at the postsynaptic membranes, which is
      regulated by trafficking of the differential PGE2 receptor subtypes in an
      activity-dependent bidirectional manner.

PMID- 17021177
TI  - Alterations in memory networks in mild cognitive impairment and Alzheimer's
      disease: an independent component analysis.
AB  - Memory function is likely subserved by multiple distributed neural networks,
      which are disrupted by the pathophysiological process of Alzheimer's disease
      (AD). In this study, we used multivariate analytic techniques to investigate
      memory-related functional magnetic resonance imaging (fMRI) activity in 52
      individuals across the continuum of normal aging, mild cognitive impairment
      (MCI), and mild AD. Independent component analyses revealed specific memory
      related networks that activated or deactivated during an associative memory
      paradigm. Across all subjects, hippocampal activation and parietal deactivation
      demonstrated a strong reciprocal relationship. Furthermore, we found evidence of
      a nonlinear trajectory of fMRI activation across the continuum of impairment.
      Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus
      compared with controls, whereas more impaired MCI subjects demonstrated
      significant hypoactivation, similar to the levels observed in the mild AD
      subjects. We found a remarkably parallel curve in the pattern of memory-related
      deactivation in medial and lateral parietal regions with greater deactivation in
      less-impaired MCI and loss of deactivation in more impaired MCI and mild AD
      subjects. Interestingly, the failure of deactivation in these regions was also
      associated with increased positive activity in a neocortical attentional network
      in MCI and AD. Our findings suggest that loss of functional integrity of the
      hippocampal-based memory systems is directly related to alterations of neural
      activity in parietal regions seen over the course of MCI and AD. These data may
      also provide functional evidence of the interaction between neocortical and
      medial temporal lobe pathology in early AD.

PMID- 17021178
TI  - Sparse representation in the human medial temporal lobe.
AB  - Recent experiments characterized individual neurons in the human medial temporal
      lobe with remarkably selective, invariant, and explicit responses to images of
      famous individuals or landmark buildings. Here, we used a probabilistic analysis
      to show that these data are consistent with a sparse code in which neurons
      respond in a selective manner to a small fraction of stimuli.

PMID- 17021179
TI  - Genetic contributions to human brain morphology and intelligence.
AB  - Variation in gray matter (GM) and white matter (WM) volume of the adult human
      brain is primarily genetically determined. Moreover, total brain volume is
      positively correlated with general intelligence, and both share a common genetic
      origin. However, although genetic effects on morphology of specific GM areas in
      the brain have been studied, the heritability of focal WM is unknown. Similarly,
      it is unresolved whether there is a common genetic origin of focal GM and WM
      structures with intelligence. We explored the genetic influence on focal GM and
      WM densities in magnetic resonance brain images of 54 monozygotic and 58
      dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used
      structural equation modeling and voxel-based morphometry. To explore the common
      genetic origin of focal GM and WM areas with intelligence, we obtained cross
      trait/cross-twin correlations in which the focal GM and WM densities of each twin
      are correlated with the psychometric intelligence quotient of his/her cotwin.
      Genes influenced individual differences in left and right superior
      occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum
      (0.82, 0.80), optic radiation (0.69, 0.79), corticospinal tract (0.78, 0.79),
      medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80),
      superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left
      postcentral cortex (0.83), left posterior cingulate cortex (0.83), right
      parahippocampal cortex (0.69), and amygdala (0.80, 0.55). Intelligence shared a
      common genetic origin with superior occipitofrontal, callosal, and left optical
      radiation WM and frontal, occipital, and parahippocampal GM (phenotypic
      correlations up to 0.35). These findings point to a neural network that shares a
      common genetic origin with human intelligence.

PMID- 17021180
TI  - A new compartment at stereocilia tips defined by spatial and temporal patterns of
      myosin IIIa expression.
AB  - Class III myosins are motor proteins that contain an N-terminal kinase domain and
      a C-terminal actin-binding domain. We show that myosin IIIa, which has been
      implicated in nonsyndromic progressive hearing loss, is localized at stereocilia
      tips. Myosin IIIa progressively accumulates during stereocilia maturation in a
      thimble-like pattern around the stereocilia tip, distinct from the cap-like
      localization of myosin XVa and the shaft localization of myosin Ic.
      Overexpression of deletion mutants for functional domains of green fluorescent
      protein (GFP)-myosin IIIa shows that the motor domain, but not the actin-binding
      tail domain, is required for stereocilia tip localization. Deletion of the kinase
      domain produces stereocilia elongation and bulging of the stereocilia tips. The
      thimble-like localization and the influence myosin IIIa has on stereocilia shape
      reveal a previously unrecognized molecular compartment at the distal end of
      stereocilia, the site of actin polymerization as well as operation of the
      mechanoelectrical transduction apparatus.

PMID- 17021181
TI  - M-like K+ currents in type I hair cells and calyx afferent endings of the
      developing rat utricle.
AB  - Type I vestibular hair cells have large K+ currents that, like neuronal M
      currents, activate negative to resting potential and are modulatable. In rodents,
      these currents are acquired postnatally. In perforated-patch recordings from rat
      utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had
      a steady-state K+ conductance (g(-30)) with a half-activation voltage (V1/2) of 
      30 mV. The size and activation range did not change in maturing type II cells,
      but, by P16, type I cells had added a K conductance that was on average fourfold
      larger and activated much more negatively. This conductance may comprise two
      components: g(-60) (V1/2 of -60 mV) and g(-80) (V1/2 of -80 mV). g(-80) washed
      out during ruptured patch recordings and was blocked by a protein kinase
      inhibitor. M currents can include contributions from KCNQ and ether-a-go-go
      related (erg) channels. KCNQ and erg channel blockers both affected the K+
      currents of type I cells, with KCNQ blockers being more potent at younger than P7
      and erg blockers more potent at older than P16. Single-cell reverse transcription
      PCR and immunocytochemistry showed expression of KCNQ and erg subunits. We
      propose that KCNQ channels contribute to g(-30) and g(-60) and erg subunits
      contribute to g(-80). Type I hair cells are contacted by calyceal afferent
      endings. Recordings from dissociated calyces and afferent endings revealed large
      K+ conductances, including a KCNQ conductance. Calyx endings were strongly
      labeled by KCNQ4 and erg1 antisera. Thus, both hair cells and calyx endings have
      large M-like K+ conductances with the potential to control the gain of
      transmission.

PMID- 17021182
TI  - NMDA-dependent, but not group I metabotropic glutamate receptor-dependent, long
      term depression at Schaffer collateral-CA1 synapses is associated with long-term
      reduction of release from the rapidly recycling presynaptic vesicle pool.
AB  - Postsynaptic alterations have been suggested to account for NMDA receptor (NMDAR)
      dependent long-term depression (LTD) and long-term potentiation of synaptic
      strength, although there is substantial evidence supporting changes in
      presynaptic release. Direct chemical activation of either NMDA or group I
      metabotropic glutamate receptor (mGluR1) elicits LTD of similar magnitudes, but
      it is unknown whether they share common expression mechanisms. Using dual-photon
      laser-scanning microscopy of FM1-43 [N-(3-triethylammoniumpropyl)-4-(4
      (dibutylamino)styryl)pyridinium dibromide] to directly visualize presynaptic
      vesicular release from the rapidly recycling vesicle pool (RRP) at Schaffer
      collateral terminals in field CA1 of rat hippocampal slices, we found that a
      persistent reduction in vesicular release from the RRP is induced by NMDA-LTD but
      not by mGluR1-LTD. Variance-mean analyses of Schaffer collateral release
      probability (P(r)) at varying extracellular calcium concentrations confirmed that
      NMDA-LTD was associated with reduced P(r), whereas mGluR1-LTD was not.
      Pharmacological isolation of NMDAR-dependent and mGluR-dependent forms of
      stimulus-evoked LTD revealed that both are composed of a combination of
      presynaptic and postsynaptic alterations. However, when group I mGluR-dependent
      LTD was isolated by combining an NMDAR blocker with a group II mGluR antagonist,
      this form of LTD was purely postsynaptic. The nitric oxide synthase inhibitor N
      omega-nitro-L-arginine blocked the induction of NMDA-LTD but did not alter mGluR
      LTD, consistent with a selective role for nitric oxide as a retrograde messenger
      mediating NMDA-LTD. These data demonstrate that single synapses can express
      multiple forms of LTD with different sites of expression, that NMDA-LTD is a
      combination of presynaptic and postsynaptic alterations, but that group I mGluR
      LTD appears to be expressed entirely postsynaptically.

PMID- 17021183
TI  - Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity
      in cell culture and intracerebral hemorrhage in mice.
AB  - The rapid loss of neurons is a major pathological outcome of intracerebral
      hemorrhage (ICH). Several mechanisms may produce the neurotoxicity observed in
      ICH, and these include proteolytic enzymes such as thrombin and matrix
      metalloproteinase-9 (MMP-9). We tested the hypothesis that thrombin and MMP-9
      combine to injure neurons in culture and that they interact to promote the acute
      neurotoxicity that occurs in ICH in vivo. We report that human fetal neurons die
      when exposed to thrombin or MMP-9 in isolation and that a combination of these
      two enzymes increased neurotoxicity. The toxicity of thrombin involved protease
      activated receptor-1 and the conversion of proMMP-9 to active MMP-9. In ICH,
      which was induced in mice by the intracerebral injection of autologous blood,
      significant areas of brain damage, neuronal death, microglia/macrophage
      activation, and neutrophil accumulation occurred by 24 h of injury. Importantly,
      these neuropathological features were reduced in MMP-9 null mice compared with
      wild-type controls, and the concordant antagonism of thrombin using hirudin also
      alleviated the injury found in MMP-9 null mice. Our collective results
      demonstrate that thrombin and MMP-9 collaborate to promote neuronal death in
      culture and in ICH. To improve the prognosis of ICH, the neurotoxic actions of
      thrombin and MMP-9 must be inhibited early and simultaneously after injury.

PMID- 17021184
TI  - Neuronal activity of histaminergic tuberomammillary neurons during wake-sleep
      states in the mouse.
AB  - Using extracellular single-unit recordings alone and in combination with
      neurobiotin juxtacellular labeling and histamine immunohistochemistry, we have
      identified, for the first time in nonanesthetized, head-restrained mice,
      histamine neurons in the tuberomammillary nuclei of the posterior hypothalamus.
      They are all characterized by triphasic broad action potentials. They are active
      only during wakefulness, and their activity is related to a high level of
      vigilance. During waking states, they display a slow (<10 Hz) tonic, repetitive,
      irregular firing pattern. Their activity varies in the different waking states,
      being lowest during quiet waking, moderate during active waking, and highest
      during attentive waking. They cease firing during quiet waking before the onset
      of EEG synchronization, the EEG sign of sleep (drowsy state), and remain silent
      during slow-wave sleep and paradoxical (or rapid eye movement) sleep. They
      exhibit a pronounced delay in firing during transitions from sleep to wakefulness
      or remain quiescent during the same transitions if the animals are not fully
      alert. They either respond with a long delay, or do not respond, to an arousing
      stimulus if the stimulus does not elicit an overt alert state. These data support
      the view that the activity of histaminergic tuberomammillary neurons plays an
      important role, not in the induction of wakefulness per se, but in the
      maintenance of the high level of vigilance necessary for cognitive processes.
      Conversely, cessation of their activity may play an important role in both the
      initiation and maintenance of sleep.

PMID- 17021185
TI  - Establishment of a rodent model of HIV-associated sensory neuropathy.
AB  - Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most
      common neurological complication of HIV infection in the current highly active
      antiretroviral therapy era. The painful sensory neuropathy is associated with the
      use of dideoxynucleoside antiretrovirals, and its development limits the choice
      of antiretroviral drugs in affected patients. There are presently no effective
      therapies for HIV-SN, and moreover there has been no robust animal model of HIV
      SN in which candidate therapeutic agents can be tested. In this paper, we show
      that we have established a rodent model of HIV-SN by oral administration of a
      dideoxynucleoside drug, didanosine, to transgenic mice expressing the HIV coat
      protein gp120 under a GFAP promoter. The neuropathy in these rodents is
      characterized by distal degeneration of unmyelinated sensory axons, similar to
      the "dying back" pattern of C-fiber loss seen in patients with HIV-SN. This model
      will be useful in examining mechanisms of distal axonal degeneration and testing
      potential neuroprotective compounds that may prevent development of the sensory
      neuropathy.

PMID- 17021186
TI  - Expression of Phox2b by brainstem neurons involved in chemosensory integration in
      the adult rat.
AB  - Central congenital hypoventilation syndrome is caused by mutations of the gene
      that encodes the transcription factor Phox2b. The syndrome is characterized by a
      severe form of sleep apnea attributed to greatly compromised central and
      peripheral chemoreflexes. In this study, we analyze whether Phox2b expression in
      the brainstem respiratory network is preferentially associated with neurons
      involved in chemosensory integration in rats. At the very rostral end of the
      ventral respiratory column (VRC), Phox2b was present in many VGlut2 (vesicular
      glutamate transporter 2) mRNA-containing neurons. These neurons were functionally
      identified as the respiratory chemoreceptors of the retrotrapezoid nucleus (RTN).
      More caudally in the VRC, many fewer neurons expressed Phox2b. These cells were
      not part of the central respiratory pattern generator (CPG), because they were
      typically cholinergic visceral motor neurons or catecholaminergic neurons
      (presumed C1 neurons). Phox2b was not detected in serotonergic neurons, in the
      A5, A6, and A7 noradrenergic cell groups nor within the main cardiorespiratory
      centers of the dorsolateral pons. Phox2b was expressed by many solitary tract
      nucleus (NTS) neurons including those that relay peripheral chemoreceptor
      information to the RTN. These and previous observations by others suggest that
      Phox2b is expressed by an uninterrupted chain of neurons involved in the
      integration of peripheral and central chemoreception (carotid bodies,
      chemoreceptor afferents, chemoresponsive NTS neurons projecting to VRC, RTN
      chemoreceptors). The presence of Phox2b in this circuit and its apparent absence
      from the respiratory CPG could explain why Phox2b mutations disrupt breathing
      automaticity during sleep without causing major impairment of respiration during
      waking.

PMID- 17021187
TI  - Functional role of GABAergic innervation of the cochlea: phenotypic analysis of
      mice lacking GABA(A) receptor subunits alpha 1, alpha 2, alpha 5, alpha 6, beta
      2, beta 3, or delta.
AB  - The olivocochlear efferent system is both cholinergic and GABAergic and
      innervates sensory cells and sensory neurons of the inner ear. Cholinergic
      effects on cochlear sensory cells are well characterized, both in vivo and in
      vitro; however, the robust GABAergic innervation is poorly understood. To explore
      the functional roles of GABA in the inner ear, we characterized the cochlear
      phenotype of seven mouse lines with targeted deletion of a GABA(A) receptor
      subunit (alpha1, alpha2, alpha5, alpha6, beta2, beta3, or delta). Four of the
      lines (alpha1, alpha2, alpha6, and delta) were normal: there was no cochlear
      histopathology, and cochlear responses suggested normal function of hair cells,
      afferent fibers, and efferent feedback. The other three lines (alpha5, beta2, and
      beta3) showed threshold elevations indicative of outer hair cell dysfunction.
      Alpha5 and beta2 lines also showed decreased effects of efferent bundle
      activation, associated with decreased density of efferent terminals on outer hair
      cells: although the onset of this degeneration was later in alpha5 (>6 weeks)
      than beta2 (<6 weeks), both lines shows normal efferent development (up to 3
      weeks). Two lines (beta2 and beta3) showed signs of neuropathy, either decreased
      density of afferent innervation (beta3) or decreased neural responses without
      concomitant attenuation of hair cell responses (beta2). One of the lines (beta2)
      showed a clear sexual dimorphism in cochlear phenotype. Results suggest that the
      GABAergic component of the olivocochlear system contributes to the long-term
      maintenance of hair cells and neurons in the inner ear.

PMID- 17021188
TI  - Intrauterine administration of autologous peripheral blood mononuclear cells
      promotes implantation rates in patients with repeated failure of IVF-embryo
      transfer.
AB  - BACKGROUND: There are few effective approaches to infertile patients with
      repeated failure in IVF-embryo transfer therapy. Since recent evidence suggests
      that some populations of maternal immune cells positively support embryo
      implantation, we have developed a new approach using peripheral blood mononuclear
      cells (PBMCs). METHODS: Patients who had not experienced successful pregnancy
      despite four or more IVF-embryo transfer sessions were enrolled in this study (n
      = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte
      retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly
      isolated from patients again, combined with cultured PBMC and then administered
      to the intrauterine cavity of the patients. Blastocyst transfer was performed on
      day 5, and the success of implantation in the PBMC-treated group was compared
      with that in the non-treated group. RESULTS: Clinical pregnancy rate,
      implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and
      35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in
      the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively).
      CONCLUSION: Intrauterine administration of autologous PBMC may be an effective
      approach to improve embryo implantation in patients with repeated IVF failures.

PMID- 17021189
TI  - Practitioner reporting of birth defects in children born following assisted
      reproductive technology: Does it still have a role in surveillance of birth
      defects?
AB  - BACKGROUND: National assisted reproductive technology (ART) data collections that
      rely on practitioners' reports of birth defects have consistently reported lower
      proportions of children with birth defects than record linkage studies that link
      ART infants to birth and malformation registers. METHODS: We compared the birth
      defect data reported to the national Australian Assisted Conception Data
      Collection (ACDC) by practitioners at three Western Australian ART clinics with
      the birth defect data identified on the Western Australian Birth Defects Registry
      (WABDR) through record linkage of all the pregnancies conceived at these clinics
      to the WABDR. Cases are reported to the WABDR by multiple statutory and voluntary
      sources. RESULTS: We found that the national ACDC significantly underestimated
      the prevalence of birth defects in WA-born ART infants. Less than one-third of
      ART children identified with a major birth defect on the WABDR were reported to
      the ACDC. CONCLUSIONS: Although national ART data collections provide valuable
      information on pregnancy rates and short-term pregnancy outcomes such as multiple
      birth and birth weight, we strongly recommend that birth defect information used
      for patient counselling is preferentially drawn from large studies that have used
      record linkage to high-quality birth defect registers.

PMID- 17021190
TI  - Quality sample collection, handling, and preservation for an effective microbial
      forensics program.

PMID- 17021191
TI  - Pleiotropic role of quorum-sensing autoinducer 2 in Photorhabdus luminescens.
AB  - Bacterial virulence is an integrative process that may involve quorum sensing. In
      this work, we compared by global expression profiling the wild-type
      entomopathogenic Photorhabdus luminescens subsp. laumondii TT01 to a luxS
      deficient mutant unable to synthesize the type 2 quorum-sensing inducer AI-2. AI
      2 was shown to regulate more than 300 targets involved in most compartments and
      metabolic pathways of the cell. AI-2 is located high in the hierarchy, as it
      controls the expression of several transcriptional regulators. The regulatory
      effect of AI-2 appeared to be dose dependent. The luxS-deficient strain exhibited
      decreased biofilm formation and increased type IV/V pilus-dependent twitching
      motility. AI-2 activated its own synthesis and transport. It also modulated
      bioluminescence by regulating the synthesis of spermidine. AI-2 was further shown
      to increase oxidative stress resistance, which is necessary to overcome part of
      the innate immune response of the host insect involving reactive oxygen species.
      Finally, we showed that the luxS-deficient strain had attenuated virulence
      against the lepidopteran Spodoptera littoralis. We concluded that AI-2 is
      involved mainly in early steps of insect invasion in P. luminescens.

PMID- 17021192
TI  - Differences in microbial activity and microbial populations of peat associated
      with suppression of damping-off disease caused by Pythium sylvaticum.
AB  - The microbiological characteristics associated with disease-suppressive peats are
      unclear. We used a bioassay for Pythium sylvaticum-induced damping-off of cress
      seedlings to identify conducive and suppressive peats. Microbial activity in
      unconditioned peats was negatively correlated with the counts of P. sylvaticum at
      the end of the bioassay. Denaturing gradient gel electrophoresis (DGGE) profiling
      and clone library analyses of small-subunit rRNA gene sequences from two
      suppressive and two conducive peats differed in the bacterial profiles generated
      and the diversity of sequence populations. There were also significant
      differences between bacterial sequence populations from suppressive and conducive
      peats. The frequencies of a number of microbial groups, including the Rhizobium
      Agrobacterium group (specifically sequences similar to those for the genera
      Ochrobactrum and Zoogloea) and the Acidobacteria, increased specifically in the
      suppressive peats, although no single bacterial group was associated with disease
      suppression. Fungal DGGE profiles varied little over the course of the bioassay;
      however, two bands associated specifically with suppressive samples were
      detected. Sequences from these bands corresponded to Basidiomycete yeast genera.
      Although the DGGE profiles were similar, fungal sequence diversity also increased
      during the bioassay. Sequences highly similar to those of Cryptococcus increased
      in relative abundance during the bioassay, particularly in the suppressive
      samples. This study highlights the importance of using complementary approaches
      to molecular profiling of complex populations and provides the first report that
      basidiomycetous yeasts may be associated with the suppression of Pythium-induced
      diseases in peats.

PMID- 17021193
TI  - Biochemical and molecular characterization of tetracycline-resistant Aeromonas
      veronii isolates from catfish.
AB  - Eighty-one tetracycline-resistant Aeromonas sp. strains were isolated from farm
      raised catfish. Morphological and biochemical characteristics indicated that 23
      of the 81 aeromonads were Aeromonas hydrophila, 7 isolates were Aeromonas trota,
      6 isolates were Aeromonas caviae, 42 isolates were Aeromonas veronii, and 3
      isolates were Aeromonas jandaei. However, the AluI and MboI restriction fragment
      length polymorphism (RFLP) patterns of the PCR-amplified 1.4-kb 16S rRNA gene
      from all 81 tetracycline-resistant aeromonads from catfish were identical to the
      RFLP banding patterns of A. veronii ATCC 35626, indicating that all 81 isolates
      were strains of A. veronii. A multiplex PCR assay successfully amplified the 5
      tetracycline-resistant genes (tetA to E) from the genomic DNA of all 81 isolates.
      The assay determined that tetE was the dominant gene occurring in 73/81 (90.0%)
      of the aeromonads. Plasmids (2.0 to 20 kb) were isolated from 33 of the 81
      isolates. Dendrogram analysis of the SpeI pulsed-field gel electrophoresis
      identified 15 distinct macrorestriction patterns among the isolates. Our results
      indicate the need for use of 16S rRNA in the identification of Aeromonas spp. and
      the prevalence of catfish as a reservoir of tet genes.

PMID- 17021194
TI  - Manganese(IV) oxide production by Acremonium sp. strain KR21-2 and extracellular
      Mn(II) oxidase activity.
AB  - Ascomycetes that can deposit Mn(III, IV) oxides are widespread in aquatic and
      soil environments, yet the mechanism(s) involved in Mn oxide deposition remains
      unclear. A Mn(II)-oxidizing ascomycete, Acremonium sp. strain KR21-2, produced a
      Mn oxide phase with filamentous nanostructures. X-ray absorption near-edge
      structure (XANES) spectroscopy showed that the Mn phase was primarily Mn(IV). We
      purified to homogeneity a laccase-like enzyme with Mn(II) oxidase activity from
      cultures of strain KR21-2. The purified enzyme oxidized Mn(II) to yield suspended
      Mn particles; XANES spectra indicated that Mn(II) had been converted to Mn(IV).
      The pH optimum for Mn(II) oxidation was 7.0, and the apparent half-saturation
      constant was 0.20 mM. The enzyme oxidized ABTS [2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid)] (pH optimum, 5.5; Km, 1.2 mM) and
      contained two copper atoms per molecule. Moreover, the N-terminal amino acid
      sequence (residues 3 to 25) was 61% identical with the corresponding sequence of
      an Acremonium polyphenol oxidase and 57% identical with that of a Myrothecium
      bilirubin oxidase. These results provide the first evidence that a fungal
      multicopper oxidase can convert Mn(II) to Mn(IV) oxide. The present study
      reinforces the notion of the contribution of multicopper oxidase to microbially
      mediated precipitation of Mn oxides and suggests that Acremonium sp. strain KR21
      2 is a good model for understanding the oxidation of Mn in diverse ascomycetes.

PMID- 17021195
TI  - Stabilization of frozen Lactobacillus delbrueckii subsp. bulgaricus in glycerol
      suspensions: Freezing kinetics and storage temperature effects.
AB  - The interactions between freezing kinetics and subsequent storage temperatures
      and their effects on the biological activity of lactic acid bacteria have not
      been examined in studies to date. This paper investigates the effects of three
      freezing protocols and two storage temperatures on the viability and
      acidification activity of Lactobacillus delbrueckii subsp. bulgaricus CFL1 in the
      presence of glycerol. Samples were examined at -196 degrees C and -20 degrees C
      by freeze fracture and freeze substitution electron microscopy. Differential
      scanning calorimetry was used to measure proportions of ice and glass transition
      temperatures for each freezing condition tested. Following storage at low
      temperatures (-196 degrees C and -80 degrees C), the viability and acidification
      activity of L. delbrueckii subsp. bulgaricus decreased after freezing and were
      strongly dependent on freezing kinetics. High cooling rates obtained by direct
      immersion in liquid nitrogen resulted in the minimum loss of acidification
      activity and viability. The amount of ice formed in the freeze-concentrated
      matrix was determined by the freezing protocol, but no intracellular ice was
      observed in cells suspended in glycerol at any cooling rate. For samples stored
      at -20 degrees C, the maximum loss of viability and acidification activity was
      observed with rapidly cooled cells. By scanning electron microscopy, these cells
      were not observed to contain intracellular ice, and they were observed to be
      plasmolyzed. It is suggested that the cell damage which occurs in rapidly cooled
      cells during storage at high subzero temperatures is caused by an osmotic
      imbalance during warming, not the formation of intracellular ice.

PMID- 17021196
TI  - Characterization of a highly hop-resistant Lactobacillus brevis strain lacking
      hop transport.
AB  - Resistance to hops is a prerequisite for lactic acid bacteria to spoil beer. In
      this study we analyzed mechanisms of hop resistance of Lactobacillus brevis at
      the metabolism, membrane physiology, and cell wall composition levels. The beer
      spoiling organism L. brevis TMW 1.465 was adapted to high concentrations of hop
      compounds and compared to a nonadapted strain. Upon adaptation to hops the
      metabolism changed to minimize ethanol stress. Fructose was used predominantly as
      a carbon source by the nonadapted strain but served as an electron acceptor upon
      adaptation to hops, with concomitant formation of acetate instead of ethanol.
      Furthermore, hop adaptation resulted in higher levels of lipoteichoic acids (LTA)
      incorporated into the cell wall and altered composition and fluidity of the
      cytoplasmic membrane. The putative transport protein HitA and enzymes of the
      arginine deiminase pathway were overexpressed upon hop adaptation. HorA was not
      expressed, and the transport of hop compounds from the membrane to the
      extracellular space did not account for increased resistance to hops upon
      adaptation. Accordingly, hop resistance is a multifactorial dynamic property,
      which can develop during adaptation. During hop adaptation, arginine catabolism
      contributes to energy and generation of the proton motive force until a small
      fraction of the population has established structural improvements. This acquired
      hop resistance is energy independent and involves an altered cell wall
      composition. LTA shields the organism from accompanying stresses and provides a
      reservoir of divalent cations, which are otherwise scarce as a result of their
      complexation by hop acids. Some of the mechanisms involved in hop resistance
      overlap with mechanisms of pH resistance and ethanol tolerance and as a result
      enable beer spoilage by L. brevis.

PMID- 17021197
TI  - General model, based on two mixed weibull distributions of bacterial resistance,
      for describing various shapes of inactivation curves.
AB  - Cells of Listeria monocytogenes or Salmonella enterica serovar Typhimurium taken
      from six characteristic stages of growth were subjected to an acidic stress (pH
      3.3). As expected, the bacterial resistance increased from the end of the
      exponential phase to the late stationary phase. Moreover, the shapes of the
      survival curves gradually evolved as the physiological states of the cells
      changed. A new primary model, based on two mixed Weibull distributions of cell
      resistance, is proposed to describe the survival curves and the change in the
      pattern with the modifications of resistance of two assumed subpopulations. This
      model resulted from simplification of the first model proposed. These models were
      compared to the Whiting's model. The parameters of the proposed model were stable
      and showed consistent evolution according to the initial physiological state of
      the bacterial population. Compared to the Whiting's model, the proposed model
      allowed a better fit and more accurate estimation of the parameters. Finally, the
      parameters of the simplified model had biological significance, which facilitated
      their interpretation.

PMID- 17021198
TI  - Babesia spp. identified by PCR in ticks collected from domestic and wild
      ruminants in southern Switzerland.
AB  - Concurrent infections with vector-borne pathogens affected a cattle herd in
      Switzerland, and one of the pathogens was identified as Babesia bigemina, which
      had never been observed in this country before. Therefore, a survey of the
      occurrence of ruminant Babesia spp. and their tick vectors in Switzerland was
      conducted. A total of 2,017 ticks were collected from sheep, goats, cattle, and
      wild ruminants (deer, roe deer, and chamois) in southern parts of Switzerland and
      identified morphologically. The vast majority of the ticks (99.2%) were Ixodes
      ricinus, but 14 ticks from sheep and goats were identified as Dermacentor
      marginatus and two ticks from wild ruminants were identified as Hemaphysalis
      punctata. PCR analyses of 700 ticks revealed the presence of Babesia divergens (n
      = 6), Babesia sp. genotype EU1 (n = 14), and B. major (n = 2), whose suggested
      occurrence was confirmed in this study by molecular analysis, and the presence of
      novel Babesia sp. genotype CH1 (n = 4), which is closely related to B. odocoilei
      and to Babesia sp. genotype RD61 reported from North America. The identification
      of B. divergens and B. major in ticks collected from wild ruminants cast doubt on
      the postulated strict host specificity of these bovine Babesia species.
      Furthermore, the zoonotic Babesia sp. genotype EU1 was detected in ticks
      collected from domestic animals but was obtained predominantly from ticks
      collected from wild ruminants. More than one tick containing DNA of different
      Babesia spp. were collected from two red deer. Hence, the role of these game
      animals as reservoir hosts of Babesia spp. seems to be important but requires
      further investigation.

PMID- 17021199
TI  - Differential effects of temperature and starvation on induction of the viable-but
      nonculturable state in the coral pathogens Vibrio shiloi and Vibrio tasmaniensis.
AB  - We compared induction of the viable-but-nonculturable (VBNC) state in two Vibrio
      spp. isolated from diseased corals by starving the cells and maintaining them in
      artificial seawater at 4 and 20 degrees C. In Vibrio tasmaniensis, isolated from
      a gorgonian octocoral growing in cool temperate water (7 to 17 degrees C), the
      VBNC state was not induced by incubation at 4 degrees C after 157 days. By
      contrast, Vibrio shiloi, isolated from a coral in warmer water (16 to 30 degrees
      C), was induced into the VBNC state by incubation at 4 degrees C after 126 days.
      This result is consistent with reports of low-temperature induction in several
      Vibrio spp. A large proportion of the V. tasmaniensis population became VBNC
      after incubation for 157 days at 20 degrees C, and V. shiloi became VBNC after
      incubation for 126 days at 20 degrees C. Resuscitation of V. shiloi cells from
      cultures at both temperatures was achieved by nutrient addition, suggesting that
      starvation plays a major role in inducing the VBNC state. Our results suggest
      that viable V. shiloi could successfully persist in the VBNC state in seawater
      for significant periods at the lower temperatures that may be experienced in
      winter conditions, which may have an effect on the seasonal incidence of coral
      bleaching. For both species, electron microscopy revealed that prolonged
      starvation resulted in transformation of the cells from rods to cocci, together
      with profuse blebbing, production of a polymer-like substance, and increased
      membrane roughness. V. shiloi cells developed an increased periplasmic space and
      membrane curling; these features were absent in V. tasmaniensis.

PMID- 17021200
TI  - Dissimilatory arsenate and sulfate reduction in sediments of two hypersaline,
      arsenic-rich soda lakes: Mono and Searles Lakes, California.
AB  - A radioisotope method was devised to study bacterial respiratory reduction of
      arsenate in sediments. The following two arsenic-rich soda lakes in California
      were chosen for comparison on the basis of their different salinities: Mono Lake
      (approximately 90 g/liter) and Searles Lake (approximately 340 g/liter). Profiles
      of arsenate reduction and sulfate reduction were constructed for both lakes.
      Reduction of [73As]arsenate occurred at all depth intervals in the cores from
      Mono Lake (rate constant [k] = 0.103 to 0.04 h(-1)) and Searles Lake (k = 0.012
      to 0.002 h(-1)), and the highest activities occurred in the top sections of each
      core. In contrast, [35S]sulfate reduction was measurable in Mono Lake (k = 7.6
      x10(4) to 3.2 x 10(-6) h(-1)) but not in Searles Lake. Sediment DNA was
      extracted, PCR amplified, and separated by denaturing gradient gel
      electrophoresis (DGGE) to obtain phylogenetic markers (i.e., 16S rRNA genes) and
      a partial functional gene for dissimilatory arsenate reduction (arrA). The
      amplified arrA gene product showed a similar trend in both lakes; the signal was
      strongest in surface sediments and decreased to undetectable levels deeper in the
      sediments. More arrA gene signal was observed in Mono Lake and was detectable at
      a greater depth, despite the higher arsenate reduction activity observed in
      Searles Lake. A partial sequence (about 900 bp) was obtained for a clone (SLAS-3)
      that matched the dominant DGGE band found in deeper parts of the Searles Lake
      sample (below 3 cm), and this clone was found to be closely related to SLAS-1, a
      novel extremophilic arsenate respirer previously cultivated from Searles Lake.

PMID- 17021201
TI  - The homologue of het-c of Neurospora crassa lacks vegetative compatibility
      function in Fusarium proliferatum.
AB  - For two fungal strains to be vegetatively compatible and capable of forming a
      stable vegetative heterokaryon they must carry matching alleles at a series of
      loci variously termed het or vic genes. Cloned het/vic genes from Neurospora
      crassa and Podospora anserina have no obvious functional similarity and have
      various cellular functions. Our objective was to identify the homologue of the
      Neurospora het-c gene in Fusarium proliferatum and to determine if this gene has
      a vegetative compatibility function in this economically important and widely
      dispersed fungal pathogen. In F. proliferatum and five other closely related
      Fusarium species we found a few differences in the DNA sequence, but the changes
      were silent and did not alter the amino acid sequence of the resulting protein.
      Deleting the gene altered sexual fertility as the female parent, but it did not
      alter male fertility or existing vegetative compatibility interactions.
      Replacement of the allele-specific portion of the coding sequence with the
      sequence of an alternate allele in N. crassa did not result in a vegetative
      incompatibility response in transformed strains of F. proliferatum. Thus, the
      fphch gene in Fusarium appears unlikely to have the vegetative compatibility
      function associated with its homologue in N. crassa. These results suggest that
      the vegetative compatibility phenotype may result from convergent evolution.
      Thus, the genes involved in this process may need to be identified at the species
      level or at the level of a group of species and could prove to be attractive
      targets for the development of antifungal agents.

PMID- 17021202
TI  - Effect on components of the intestinal microflora and plasma neuropeptide levels
      of feeding Lactobacillus delbrueckii, Bifidobacterium lactis, and inulin to adult
      and elderly rats.
AB  - The aim of this study was to compare the effects of the mixture of Lactobacillus
      delbrueckii subsp. rhamnosus strain GG, Bifidobacterium lactis Bb12, and inulin
      on intestinal populations of lactobacilli, bifidobacteria, and enterobacteria in
      adult and elderly rats fed the same (in quality and quantity) diet. The portal
      plasma levels of two neuropeptides, neuropeptide Y (NPY) and peptide YY (PYY),
      were also evaluated to assess the physiological consequences of the synbiotic
      treatment for the gastrointestinal (GI) tracts of rats of different ages. Adult
      (n = 24) and elderly (n = 24) male rats were fed the AIN-93 M maintenance diet.
      After 2 weeks of adaptation, the diet of 12 rats of each age group was
      supplemented with 8% inulin and with strains GG and Bb12 to provide 2.2 x 10(9)
      CFU of each strain g(-1) of the diet. Blood and different regions of the GI tract
      were sampled from all rats after 21 days of the treatment. Treatment with the
      mixture of strain GG, strain BB12, and inulin induced significantly different
      changes in the numbers of lactobacilli, bifidobacteria, and enterobacteria of the
      stomach, small intestine, cecum, and colon microflora. Moreover, the GG, BB12,
      and inulin mixture increased the concentrations of NPY and PYY for adult rats.
      For the elderly animals, the PYY concentration was not changed, while the NPY
      concentration was decreased by treatment with the GG, BB12, and inulin mixture.
      The results of the present study indicate that the physiological status of the GI
      tract, and not just diet, has a major role in the regulation of important groups
      of the GI bacteria community, since even the outcome of the dietary modification
      with synbiotics depends on the ages of the animals.

PMID- 17021203
TI  - Alteration of the canine small-intestinal lactic acid bacterium microbiota by
      feeding of potential probiotics.
AB  - Five potentially probiotic canine fecal lactic acid bacterium (LAB) strains,
      Lactobacillus fermentum LAB8, Lactobacillus salivarius LAB9, Weissella confusa
      LAB10, Lactobacillus rhamnosus LAB11, and Lactobacillus mucosae LAB12, were fed
      to five permanently fistulated beagles for 7 days. The survival of the strains
      and their potential effects on the indigenous intestinal LAB microbiota were
      monitored for 17 days. Denaturing gradient gel electrophoresis (DGGE)
      demonstrated that the five fed LAB strains survived in the upper gastrointestinal
      tract and modified the dominant preexisting indigenous jejunal LAB microbiota of
      the dogs. When the LAB supplementation was ceased, DGGE analysis of jejunal chyme
      showed that all the fed LAB strains were undetectable after 7 days. However, the
      diversity of the intestinal indigenous microbiota of the dogs, as characterized
      from jejunal chyme plated on Lactobacillus selective medium without acetic acid,
      was reduced and did not return to the original level during the study period. In
      all but one dog, an indigenous Lactobacillus acidophilus strain emerged as the
      dominant LAB strain. In conclusion, strains LAB8 to LAB12 have potential as
      probiotic strains for dogs as they survive in and dominate the jejunal LAB
      microbiota during feeding and have the ability to modify the intestinal
      microbiota.

PMID- 17021205
TI  - Generation of useful insertionally blocked sterol degradation pathway mutants of
      fast-growing mycobacteria and cloning, characterization, and expression of the
      terminal oxygenase of the 3-ketosteroid 9alpha-hydroxylase in Mycobacterium
      smegmatis mc(2)155.
AB  - Integration of the pCG79 temperature-sensitive plasmid carrying Tn611 was used to
      generate libraries of mutants with blocked sterol-transforming ability of the
      sterol-utilizing strains Mycobacterium smegmatis mc(2)155 and Mycobacterium phlei
      M51-Ept. Of the 10,000 insertional mutants screened from each library, 4 strains
      with altered activity of the sterol-degrading enzymes were identified. A blocked
      4-androstene-3,17-dione-producing M. phlei mutant transformed sitosterol to 23,24
      dinorcholane derivatives that are useful starting materials for corticosteroid
      syntheses. A recombinant plasmid, pFJ92, was constructed from the genomic DNA of
      one of the insertional mutants of M. smegmatis, 10A12, which was blocked in 3
      ketosteroid 9alpha-hydroxylation and carrying the transposon insertion and
      flanking DNA sequences, and used to isolate a chromosomal fragment encoding the
      9alpha-hydroxylase. The open reading frame encodes the 383-amino-acid terminal
      oxygenase of 3-ketosteroid 9alpha-hydroxylase in M. smegmatis mc(2)155 and has
      domains typically conserved in class IA terminal oxygenases. Escherichia coli
      containing the gene could hydroxylate the steroid ring at the 9alpha position.

PMID- 17021204
TI  - Pheromone-responsive conjugative vancomycin resistance plasmids in Enterococcus
      faecalis isolates from humans and chicken feces.
AB  - The drug resistances and plasmid contents of a total of 85 vancomycin-resistant
      enterococcus (VRE) strains that had been isolated in Korea were examined. Fifty
      four of the strains originated from samples of chicken feces, and 31 were
      isolated from hospital patients in Korea. Enterococcus faecalis KV1 and KV2,
      which had been isolated from a patient and a sample of chicken feces,
      respectively, were found to carry the plasmids pSL1 and pSL2, respectively. The
      plasmids transferred resistances to vancomycin, gentamicin, kanamycin,
      streptomycin, and erythromycin to E. faecalis strains at a high frequency of
      about 10(-3) per donor cell during 4 hours of broth mating. E. faecalis strains
      containing each of the pSL plasmids formed clumps after 2 hours of incubation in
      broth containing E. faecalis FA2-2 culture filtrate (i.e., the E. faecalis sex
      pheromone), and the plasmid subsequently transferred to the recipient strain in a
      10-min short mating in broth, indicating that the plasmids are responsive to E.
      faecalis pheromones. The pSL plasmids did not respond to any of synthetic
      pheromones for the previously characterized plasmids. The pheromone specific for
      pSL plasmids has been designated cSL1. Southern hybridization analysis showed
      that specific FspI fragments from each of the pSL plasmids hybridized with the
      aggregation substance gene (asa1) of the pheromone-responsive plasmid pAD1,
      indicating that the plasmids had a gene homologous to asa1. The restriction maps
      of the plasmids were identical, and the size of the plasmids was estimated to be
      128.1 kb. The plasmids carried five drug resistance determinants for vanA, ermB,
      aph(3'), aph(6'), and aac(6')/aph(2'), which encode resistance to vancomycin,
      erythromycin, kanamycin, streptomycin, and gentamicin/kanamycin, respectively.
      Nucleotide sequence analyses of the drug resistance determinants and their
      flanking regions are described in this report. The results described provide
      evidence for the exchange of genetic information between human and animal
      (chicken) VRE reservoirs and suggest the potential for horizontal transmission of
      multiple drug resistance, including vancomycin resistance, between farm animals
      and humans via a pheromone-responsive conjugative plasmid.

PMID- 17021206
TI  - Blooms of single bacterial species in a coastal lagoon of the southwestern
      Atlantic Ocean.
AB  - We investigated seasonal differences in community structure and activity (leucine
      incorporation) of the planktonic bacterial assemblage in the freshwater and
      brackish-water zones of a shallow coastal lagoon of the southwestern Atlantic
      Ocean. Alphaproteobacteria formed the dominant microbial group in both zones
      throughout the sampling period. After an intrusion of marine water, members of
      the SAR11 lineage became abundant in the brackish-water zone. These bacteria were
      apparently distributed over the lagoon during the following months until they
      constituted almost 30% of all prokaryotic cells at both sampling sites. At the
      first sampling date (March 2003) a single alphaproteobacterial species unrelated
      to SAR11, Sphingomonas echinoides, dominated the microbial assemblages in both
      zones of the lagoon concomitantly with a bloom of filamentous cyanobacteria.
      Pronounced maxima of leucine incorporation were observed once in each zone of the
      lagoon. In the freshwater zone, this highly active microbial assemblage was a mix
      of the typical bacteria lineages expected in aquatic systems. By contrast, a
      single bacterial genotype with >99% similarity to the facultative pathogen
      gammaproteobacterial species Stenotrophomonas maltophilia formed >90% of the
      bacterial assemblage (>10(7) cell ml(-1)) in the brackish-water zone at the time
      point of highest bacterial leucine incorporation. Moreover, these bacteria were
      equally dominant, albeit less active, in the freshwater zone. Thus, the pelagic
      zone of the studied lagoon harbored repeated short-term blooms of single
      bacterial species. This finding may have consequences for environmental
      protection.

PMID- 17021207
TI  - The AauR-AauS two-component system regulates uptake and metabolism of acidic
      amino acids in Pseudomonas putida.
AB  - Pseudomonas putida KT2440 metabolizes a wide range of carbon and nitrogen
      sources, including many amino acids. In this study, a sigma54-dependent two
      component system that controls the uptake and metabolism of acidic amino acids
      was identified. The system (designated aau, for acidic amino acid utilization)
      involves a sensor histidine kinase, AauS, encoded by PP1067, and a response
      regulator, AauR, encoded by PP1066. aauR and aauS deletion mutants were unable to
      efficiently utilize aspartate (Asp), glutamate (Glu), and glutamine (Gln) as sole
      sources of carbon and nitrogen. Growth of the mutants was partially restored when
      the above-mentioned amino acids were supplemented with glucose or succinate as an
      additional carbon source. Uptake of Gln, Asp, and asparagine (Asn) by the aauR
      mutant was moderately reduced, while Glu uptake was severely impaired. In the
      absence of glucose, the aauR mutant even secreted Glu into the medium.
      Furthermore, disruption of aauR affected the activities of several key enzymes of
      Glu and Asp metabolism, leading to the intracellular accumulation of Glu and
      greatly reduced survival times under conditions of nitrogen starvation. By a
      proteomics approach, four major proteins were identified that are downregulated
      during growth of the aauR mutant on Glu. Two of these were identified as
      periplasmic glutaminase/asparaginase and the solute-binding protein of a Glu/Asp
      transporter. Transcriptional analysis of lacZ fusions containing the putative
      promoter regions of these genes confirmed that their expression is indeed
      affected by the aau system. Three further periplasmic solute-binding proteins
      were strongly expressed during growth of the aauR deletion mutant on Glu but
      downregulated during cultivation on glucose/NH4+. These systems may be involved
      in amino acid efflux.

PMID- 17021208
TI  - Synthetic statistical approach reveals a high degree of richness of microbial
      eukaryotes in an anoxic water column.
AB  - Molecular surveys suggest that communities of microbial eukaryotes are remarkably
      rich, because even large clone libraries seem to capture only a minority of
      species. This provides a qualitative picture of protistan richness but does not
      measure its real extent either locally or globally. Statistical analysis can
      estimate a community's richness, but the specific methods used to date are not
      always well grounded in statistical theory. Here we study a large protistan
      molecular survey from an anoxic water column in the Cariaco Basin (Caribbean
      Sea). We group individual 18S rRNA gene sequences into operational taxonomic
      units (OTUs) using different cutoff values for sequence similarity (99 to 50%)
      and systematically apply parametric models and nonparametric estimators to the
      OTU frequency data to estimate the total protistan diversity. The parametric
      models provided statistically sound estimates of protistan richness, with
      biologically meaningful standard errors, maximal data usage, and extensive model
      diagnostics and were preferable to the available nonparametric tools. Our clone
      library exceeded 700 clones but still covered only a minority of species and less
      than half of the larger protistan clades. Our estimates of total protistan
      richness portray the target community as very rich at all OTU levels, with
      hundreds of different populations apparently co-occurring in the small (3-liter)
      volume of our sample, as well as dozens of clades of the highest taxonomic order.
      These estimates are among the first for microbial eukaryotes that are obtained
      using state-of-the-art statistical methods and can serve as benchmark numbers for
      the local diversity of protists.

PMID- 17021210
TI  - Immunoquantitative real-time PCR for detection and quantification of
      Staphylococcus aureus enterotoxin B in foods.
AB  - A real-time immunoquantitative PCR (iqPCR) method for detection of Staphylococcus
      aureus enterotoxin B (SEB) was developed and evaluated using both pure cultures
      and foods. The assay consisted of immunocapture of SEB and real-time PCR
      amplification of the DNA probe linked to the detection antibody. iqPCR was
      compared to an in-house enzyme-linked immunosorbent assay (ELISA) using the same
      couple of capture-detection antibodies and to commercial kits for detection of S.
      aureus enterotoxins (SE). The iqPCR was approximately 1,000 times more sensitive
      (<10 pg ml(-1)) than the in-house ELISA and had a dynamic range of approximately
      10 pg ml(-1) to approximately 30,000 pg ml(-1). iqPCR was not inhibited by any of
      the foods tested and was able to detect SEB present in these foods. No cross
      reactivity with SE other than SEB was observed. Application of iqPCR for
      detection of SEB in cultures of S. aureus revealed the onset of SEB production
      after 4 h of incubation at 22, 37, and 42 degrees C, which was in the first half
      of the exponential growth phase. The total amounts of SEB produced by the two
      strains tested were larger at 42 degrees C than at 37 degrees C and were strain
      dependent.

PMID- 17021209
TI  - Occurrence of sep insecticidal toxin complex genes in Serratia spp. and Yersinia
      frederiksenii.
AB  - Some strains of Serratia entomophila and S. proteamaculans cause amber disease of
      the grass grub Costelytra zealandica (Coleoptera: Scarabaeidae). Three genes
      required for virulence, sepABC, are located on a large plasmid, pADAP. Sequence
      analysis suggests that the sepABC gene cluster may be part of a horizontally
      mobile region. This study presents evidence for the putative mobility of the sep
      genes of pADAP. Southern blot analysis showed that orthologues of the sep genes
      reside on plasmids within S. entomophila, S. liquefaciens, S. proteamaculans, and
      a plasmid from Yersinia frederiksenii. Three plasmids hybridized to the pADAP sep
      virulence-associated region but not the pADAP replication and conjugation
      regions. Subsequent DNA sequence analysis of the Y. frederiksenii sep-like genes,
      designated tcYF1 and tcYF2, showed that they had 88% and 87% DNA identity to sepA
      and sepB, respectively. These results indicate that the sep genes are part of a
      discrete horizontally mobile region.

PMID- 17021211
TI  - Photolyase confers resistance to UV light but does not contribute to the
      symbiotic benefit of bioluminescence in Vibrio fischeri ES114.
AB  - Recent reports suggest that the selective advantage of bioluminescence for
      bacteria is mediated by light-dependent stimulation of photolyase to repair DNA
      lesions. Despite evidence for this model, photolyase mutants have not been
      characterized in a naturally bioluminescent bacterium, nor has this hypothesis
      been tested in bioluminescent bacteria under natural conditions. We have now
      characterized the photolyase encoded by phr in the bioluminescent bacterium
      Vibrio fischeri ES114. Consistent with Phr possessing photolyase activity, phr
      conferred light-dependent resistance to UV light. However, upon comparing ES114
      to a phr mutant and a dark Delta luxCDABEG mutant, we found that bioluminescence
      did not detectably affect photolyase-mediated resistance to UV light. Addition of
      the light-stimulating autoinducer N-3-oxo-hexanoyl homoserine lactone appeared to
      increase UV resistance, but this was independent of photolyase or
      bioluminescence. Moreover, although bioluminescence confers an advantage for V.
      fischeri during colonization of its natural host, Euprymna scolopes, the phr
      mutant colonized this host to the same level as the wild type. Taken together,
      our results indicate that at least in V. fischeri strain ES114, the benefits of
      bioluminescence during symbiotic colonization are not mediated by photolyase, and
      although some UV resistance mechanism may be coregulated with bioluminescence, we
      found no evidence that light production benefits cells by stimulating photolyase
      in this strain.

PMID- 17021212
TI  - Coping with polychlorinated biphenyl (PCB) toxicity: Physiological and genome
      wide responses of Burkholderia xenovorans LB400 to PCB-mediated stress.
AB  - The biodegradation of polychlorinated biphenyls (PCBs) relies on the ability of
      aerobic microorganisms such as Burkholderia xenovorans sp. LB400 to tolerate two
      potential modes of toxicity presented by PCB degradation: passive toxicity, as
      hydrophobic PCBs potentially disrupt membrane and protein function, and
      degradation-dependent toxicity from intermediates of incomplete degradation. We
      monitored the physiological characteristics and genome-wide expression patterns
      of LB400 in response to the presence of Aroclor 1242 (500 ppm) under low
      expression of the structural biphenyl pathway (succinate and benzoate growth) and
      under induction by biphenyl. We found no inhibition of growth or change in fatty
      acid profile due to PCBs under nondegrading conditions. Moreover, we observed no
      differential gene expression due to PCBs themselves. However, PCBs did have a
      slight effect on the biosurface area of LB400 cells and caused slight membrane
      separation. Upon activation of the biphenyl pathway, we found growth inhibition
      from PCBs beginning after exponential-phase growth suggestive of the accumulation
      of toxic compounds. Genome-wide expression profiling revealed 47 differentially
      expressed genes (0.56% of all genes) under these conditions. The biphenyl and
      catechol pathways were induced as expected, but the quinoprotein methanol
      metabolic pathway and a putative chloroacetaldehyde dehydrogenase were also
      highly expressed. As the latter protein is essential to conversion of toxic
      metabolites in dichloroethane degradation, it may play a similar role in the
      degradation of chlorinated aliphatic compounds resulting from PCB degradation.

PMID- 17021213
TI  - A homolog of Bacillus subtilis trigger factor in Listeria monocytogenes is
      involved in stress tolerance and bacterial virulence.
AB  - Molecular chaperones play an essential role in the folding of nascent chain
      polypeptides, as well as in the refolding and degradation of misfolded or
      aggregated proteins. They also assist in protein translocation and participate in
      stress functions. We identified a gene, designated tig, encoding a protein
      homologous to trigger factor (TF), a cytosolic ribosome-associated chaperone, in
      the genome of Listeria monocytogenes. We constructed a chromosomal Delta tig
      deletion and evaluated the impact of the mutation on bacterial growth in broth
      under various stress conditions and on pathogenesis. The Delta tig deletion did
      not affect cell viability but impaired survival in the presence of heat and
      ethanol stresses. We also identified the ffh gene, encoding a protein homologous
      to the SRP54 eukaryotic component of the signal recognition particle. However, a
      Delta ffh deletion was not tolerated, suggesting that Ffh is essential, as it is
      in Bacillus subtilis and Escherichia coli. Thus, although dispensable for growth,
      TF is involved in the stress response of L. monocytogenes. The Delta tig mutant
      showed no or very modest intracellular survival defects in eukaryotic cells.
      However, in vivo it showed a reduced capacity to persist in the spleens and
      livers of infected mice, revealing that TF has a role in the pathogenicity of L.
      monocytogenes.

PMID- 17021214
TI  - Genetic and phenotypic variability among Salmonella enterica serovar Typhimurium
      isolates from California dairy cattle and humans.
AB  - Fifty-six human and 24 adult dairy cattle isolates of Salmonella enterica serovar
      Typhimurium from a single county in California were compared using ribotyping,
      insertion sequence typing (IS200), pulsed-field gel electrophoresis, plasmid
      typing, phage typing, and antimicrobial resistance testing. The majority of the
      isolates fell into one of two groups which were phage types DT104 and DT193.
      Combining the information from all typing methods, a total of 45 different
      "clusters" were defined, with 35 of those including only a single isolate. The
      library of isolates had a high degree of variability, but antibiotic resistance
      and plasmid typing each defined single clusters in which human or bovine isolates
      predominated (chi2, P < 0.05).

PMID- 17021215
TI  - Molecular comparisons of freshwater and marine isolates of the same morphospecies
      of heterotrophic flagellates.
AB  - Heterotrophic flagellates are key components of all ecosystems. Understanding the
      patterns of biodiversity of these organisms is thus particularly important. Here
      we analyzed the intraspecific diversity of 10 morphospecies of heterotrophic
      flagellates comprising representatives of the Apusozoa (2 morphospecies) and
      Kinetoplastea (8 morphospecies), all belonging to the most common flagellates
      with worldwide distribution. Most morphospecies showed a mixing of lineages
      isolated from diverse habitats, indicating that some lineages of these
      morphospecies had been able to colonize different habitats several times.
      Furthermore, our results revealed remarkable levels of genetic divergence within
      most of the morphospecies studied, underlining the difficulty of correctly
      determining species by means of morphology alone. Many cryptic or pseudocryptic
      species seem to occur. Our results revealed clear divergence between marine and
      freshwater lineages of the morphospecies Ancyromonas sigmoides, showing that
      freshwater lineages have not been able to colonize marine environments and marine
      lineages have not been able to colonize freshwater environments for a long time.

PMID- 17021216
TI  - Combinatorial biosynthesis of antitumor deoxysugar pathways in Streptomyces
      griseus: Reconstitution of "unnatural natural gene clusters" for the biosynthesis
      of four 2,6-D-dideoxyhexoses.
AB  - Combinatorial biosynthesis was applied to Streptomyces deoxysugar biosynthesis
      genes in order to reconstitute "unnatural natural gene clusters" for the
      biosynthesis of four D-deoxysugars (D-olivose, D-oliose, D-digitoxose, and D
      boivinose). Expression of these gene clusters in Streptomyces albus 16F4 was used
      to prove the functionality of the designed clusters through the generation of
      glycosylated tetracenomycins. Three glycosylated tetracenomycins were generated
      and characterized, two of which (D-digitoxosyl-tetracenomycin C and D-boivinosyl
      tetracenocmycin C) were novel compounds. The constructed gene clusters may be
      used to increase the capabilities of microorganisms to synthesize new deoxysugars
      and therefore to produce new glycosylated bioactive compounds.

PMID- 17021217
TI  - Complete sequence of the enterocin Q-encoding plasmid pCIZ2 from the multiple
      bacteriocin producer Enterococcus faecium L50 and genetic characterization of
      enterocin Q production and immunity.
AB  - The locations of the genetic determinants for enterocin L50 (EntL50A and
      EntL50B), enterocin Q (EntQ), and enterocin P (EntP) in the multiple bacteriocin
      producer Enterococcus faecium strain L50 were determined. These bacteriocin genes
      occur at different locations; entL50AB (encoding EntL50A and EntL50B) are on the
      50-kb plasmid pCIZ1, entqA (encoding EntQ) is on the 7.4-kb plasmid pCIZ2, and
      entP (encoding EntP) is on the chromosome. The complete nucleotide sequence of
      pCIZ2 was determined to be 7,383 bp long and contains 10 putative open reading
      frames (ORFs) organized in three distinct regions. The first region contains
      three ORFs: entqA preceded by two divergently oriented genes, entqB and entqC.
      EntqB shows high levels of similarity to bacterial ATP-binding cassette (ABC)
      transporters, while EntqC displays no significant similarity to any known
      protein. The second region encompasses four ORFs (orf4 to orf7), and ORF4 and
      ORF5 display high levels of similarity to mobilization proteins from E. faecium
      and Enterococcus faecalis. In addition, features resembling a transfer origin
      region (oriT) were found in the promoter area of orf4. The third region contains
      three ORFs (orf8 to orf10), and ORF8 and ORF9 exhibit similarity to the
      replication initiator protein RepE from E. faecalis and to RepB proteins,
      respectively. To clarify the minimum requirement for EntQ synthesis, we subcloned
      and heterologously expressed a 2,371-bp fragment from pCIZ2 that encompasses only
      the entqA, entqB, and entqC genes in Lactobacillus sakei, and we demonstrated
      that this fragment is sufficient for EntQ production. Moreover, we also obtained
      experimental results indicating that EntqB is involved in ABC transporter
      mediated EntQ secretion, while EntqC confers immunity to this bacteriocin.

PMID- 17021218
TI  - Prevalence of a non-male-killing spiroplasma in natural populations of Drosophila
      hydei.
AB  - Male-killing phenotypes are found in a variety of insects and are often
      associated with maternally inherited endosymbiotic bacteria. In several species
      of Drosophila, male-killing endosymbionts of the genus Spiroplasma have been
      found at low frequencies (0.1 to 3%). In this study, spiroplasma infection
      without causing male-killing was shown to be prevalent (23 to 66%) in Japanese
      populations of Drosophila hydei. Molecular phylogenetic analyses showed that D.
      hydei was infected with a single strain of spiroplasma, which was closely related
      to male-killing spiroplasmas from other Drosophila species. Artificial-transfer
      experiments suggested that the spiroplasma genotype rather than the host genotype
      was responsible for the absence of the male-killing phenotype. Infection
      densities of the spiroplasma in the natural host, D. hydei, and in the artificial
      host, Drosophila melanogaster, were significantly lower than those of the male
      killing spiroplasma NSRO, which was in accordance with the hypothesis that a
      threshold infection density is needed for the spiroplasma-induced male-killing
      expression.

PMID- 17021219
TI  - Virulence factor gene profiles of Escherichia coli isolates from clinically
      healthy pigs.
AB  - Nonpathogenic, intestinal Escherichia coli (commensal E. coli) supports the
      physiological intestinal balance of the host, whereas pathogenic E. coli with
      typical virulence factor gene profiles can cause severe outbreaks of diarrhea. In
      many reports, E. coli isolates from diarrheic animals were classified as putative
      pathogens. Here we describe a broad variety of virulence gene-positive E. coli
      isolates from swine with no clinical signs of intestinal disease. The isolation
      of E. coli from 34 pigs from the same population and the testing of 331 isolates
      for genes encoding heat-stable enterotoxins I and II, heat-labile enterotoxin I,
      Shiga toxin 2e, and F4, F5, F6, F18, and F41 fimbriae revealed that 68.6% of the
      isolates were positive for at least one virulence gene, with a total of 24
      different virulence factor gene profiles, implying high rates of horizontal gene
      transfer in this E. coli population. Additionally, we traced the occurrence of
      hemolytic E. coli over a period of 1 year in this same pig population. Hemolytic
      isolates were differentiated into seven clones; only three were found to harbor
      virulence genes. Hemolytic E. coli isolates without virulence genes or with only
      the fedA gene were found to be nontypeable by slide agglutination tests with OK
      antisera intended for screening live cultures against common pathogenic E. coli
      serogroups. The results appear to indicate that virulence gene-carrying E. coli
      strains are a normal part of intestinal bacterial populations and that high
      numbers of E. coli cells harboring virulence genes and/or with hemolytic activity
      do not necessarily correlate with disease.

PMID- 17021220
TI  - Cultivation-independent examination of horizontal transfer and host range of an
      IncP-1 plasmid among gram-positive and gram-negative bacteria indigenous to the
      barley rhizosphere.
AB  - The host range and transfer frequency of an IncP-1 plasmid (pKJK10) among
      indigenous bacteria in the barley rhizosphere was investigated. A new flow
      cytometry-based cultivation-independent method for enumeration and sorting of
      transconjugants for subsequent 16S rRNA gene classification was used. Indigenous
      transconjugant rhizosphere bacteria were collected by fluorescence-activated cell
      sorting and identified by cloning and sequencing of 16S rRNA genes from the
      sorted cells. The host range of the pKJK10 plasmid was exceptionally broad, as it
      included not only bacteria belonging to the alpha, beta, and gamma subclasses of
      the Proteobacteria, but also Arthrobacter sp., a gram-positive member of the
      Actinobacteria. The transfer frequency (transconjugants per donor) from the
      Pseudomonas putida donor to the indigenous bacteria was 7.03 x 10(-2) +/- 3.84 x
      10(-2). This is the first direct documentation of conjugal transfer between gram
      negative donor and gram-positive recipient bacteria in situ.

PMID- 17021221
TI  - Mineralization of paraoxon and its use as a sole C and P source by a rationally
      designed catabolic pathway in Pseudomonas putida.
AB  - Organophosphate compounds, which are widely used as pesticides and chemical
      warfare agents, are cholinesterase inhibitors. These synthetic compounds are
      resistant to natural degradation and threaten the environment. We constructed a
      strain of Pseudomonas putida that can efficiently degrade a model
      organophosphate, paraoxon, and use it as a carbon, energy, and phosphorus source.
      This strain was engineered with the pnp operon from Pseudomonas sp. strain
      ENV2030, which encodes enzymes that transform p-nitrophenol into beta
      ketoadipate, and with a synthetic operon encoding an organophosphate hydrolase
      (encoded by opd) from Flavobacterium sp. strain ATCC 27551, a phosphodiesterase
      (encoded by pde) from Delftia acidovorans, and an alkaline phosphatase (encoded
      by phoA) from Pseudomonas aeruginosa HN854 under control of a constitutive
      promoter. The engineered strain can efficiently mineralize up to 1 mM (275
      mg/liter) paraoxon within 48 h, using paraoxon as the sole carbon and phosphorus
      source and an inoculum optical density at 600 nm of 0.03. Because the organism
      can utilize paraoxon as a sole carbon, energy, and phosphorus source and because
      one of the intermediates in the pathway (p-nitrophenol) is toxic at high
      concentrations, there is no need for selection pressure to maintain the
      heterologous pathway.

PMID- 17021223
TI  - Metschnikowia strains isolated from botrytized grapes antagonize fungal and
      bacterial growth by iron depletion.
AB  - Noble-rotted grapes are colonized by complex microbial populations. I isolated
      pigment-producing Metschnikowia strains from noble-rotted grapes that had
      antagonistic activity against filamentous fungi, yeasts, and bacteria. A red
      maroon pigment was formed from a diffusible colorless precursor released by the
      cells into the medium. The conversion of the precursor required iron and could
      occur both in the cells (red colonies) and in the medium (red halos around
      colonies). The intensity of pigmentation was correlated with the intensity of the
      antimicrobial activity. Mutants that did not form pigment also lacked antifungal
      activity. Within the pigmented halos, conidia of the sensitive fungi did not
      germinate, and their hyphae did not grow and frequently lysed at the tips.
      Supplementation of the medium with iron reduced the size of the halos and the
      inhibition zones, while it increased the pigment accumulation by the colonies.
      The iron-binding agent tropolone had a similar effect, so I hypothesize that
      pigmented Metschnikowia isolates inhibit the growth of the sensitive
      microorganisms by pigment formation, which depletes the free iron in the medium.
      As the pigment is a large nondiffusible complex produced in the presence of both
      low and high concentrations of ferric ions, the proposed mechanism is different
      from the mechanisms operating in microbes that release siderophores into the
      environment for iron acquisition.

PMID- 17021224
TI  - Use of flow cytometry to follow the physiological states of microorganisms in
      cider fermentation processes.
AB  - The flow cytometry (FC) technique used with certain fluorescent dyes (ChemChrome
      V6 [CV6], DRAQ5, and PI) has proven useful to label and to detect different
      physiological states of yeast and malolactic bacterium starters conducting cider
      fermentation over time (by performing sequential inoculation of microorganisms).
      First, the technique was tested with pure cultures of both types of
      microorganisms grown in synthetic media under different induced stress
      conditions. Metabolically active cells detected by FC and by the standard plate
      counting method for both types of microorganisms in fresh overnight pure cultures
      gave good correlations between the two techniques in samples taken at this stage.
      Otherwise, combining the results obtained by FC and plating during alcoholic and
      malolactic fermentation over time in the cider-making process, different
      subpopulations were detected, showing significant differences between the
      methods. A small number of studies have applied the FC technique to analyze
      fermentation processes and mixed cultures over time. The results were used to
      postulate equations explaining the different physiological states in cell
      populations taken from fresh, pure overnight cultures under nonstress conditions
      or cells subjected to stress conditions over time, either under a pure-culture
      fermentation process (in this work, corresponding to alcoholic fermentation) or
      under mixed-fermentation conditions (for the malolactic-fermentation phase), that
      could be useful to improve the control of the processes.

PMID- 17021222
TI  - Culture-independent analysis of indomethacin-induced alterations in the rat
      gastrointestinal microbiota.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for a
      variety of inflammatory conditions; however, the benefits of this class of drugs
      are accompanied by deleterious side effects, most commonly gastric irritation and
      ulceration. NSAID-induced ulceration is thought to be exacerbated by intestinal
      microbiota, but previous studies have not identified specific microbes that
      contribute to these adverse effects. In this study, we conducted a culture
      independent analysis of approximately 1,400 bacterial small-subunit rRNA genes
      associated with the small intestines and mesenteric lymph nodes of rats treated
      with the NSAID indomethacin. This is the first molecular analysis of the
      microbiota of the rat small intestine. A comparison of clone libraries and
      species-specific quantitative PCR results from rats treated with indomethacin and
      untreated rats revealed that organisms closely related to Enterococcus faecalis
      were heavily enriched in the small intestine and mesenteric lymph nodes of the
      treated rats. These data suggest that treatment of NSAID-induced ulceration may
      be facilitated by addressing the microbiological imbalances.

PMID- 17021225
TI  - Multiparameter assessments to determine the effects of sugars and antimicrobials
      on a polymicrobial oral biofilm.
AB  - Clinical studies indicate relationships between dental plaque, a naturally formed
      biofilm, and oral diseases. The crucial role of nonmicrobial biofilm constituents
      in maintaining biofilm structure and biofilm-specific attributes, such as
      resistance to shear and viscoelasticity, is increasingly recognized. Concurrent
      analyses of the diverse nonmicrobial biofilm components for multiparameter
      assessments formed the focus of this investigation. Comparable numbers of
      Actinomyces viscosus, Streptococcus sanguinis, Streptococcus mutans, Neisseria
      subflava, and Actinobacillus actinomycetemcomitans cells were seeded into
      multiple wells of 96-well polystyrene plates for biofilm formation. Quantitative
      fluorescence and confocal laser scanning microscopy (CLSM) examined the
      influences of dietary sugars, incubation conditions, ingredients in oral hygiene
      formulations, and antibiotics on biofilm components. Biofilm extracellular
      polymeric substances (EPS) were examined with an optimized mixture of fluorescent
      lectins, with biofilm proteins, lipids, and nucleic acids detected with specific
      fluorescent stains. Anaerobic incubation of biofilms resulted in significantly
      more biofilm EPS and extractable carbohydrates than those formed under aerobic
      conditions (P < 0.05). Sucrose significantly enhanced biofilm EPS in comparison
      to fructose, galactose, glucose, and lactose (P < 0.05). CLSM demonstrated
      thicker biofilms under sucrose-replete conditions, along with significant
      increases in biofilm EPS, proteins, lipids, and nucleic acids, than under
      conditions of sucrose deficiency (P < 0.05). Agents in oral hygiene formulations
      (chlorhexidine, ethanol, and sodium lauryl sulfate), a mucolytic agent (N-acetyl
      L-cysteine), and antibiotics with different modes of action (amoxicillin,
      doxycycline, erythromycin, metronidazole, and vancomycin) inhibited biofilm
      components (P < 0.05). Multiparameter analysis indicated a dose-dependent
      inhibition of biofilm EPS and protein by chlorhexidine and sodium lauryl sulfate,
      along with distinctive inhibitory patterns for subinhibitory concentrations of
      antibiotics. Collectively, these results highlight multiparameter assessments as
      a broad platform for simultaneous assessment of diverse biofilm components.

PMID- 17021226
TI  - Eukaryotic lipid body proteins in oleogenous actinomycetes and their targeting to
      intracellular triacylglycerol inclusions: Impact on models of lipid body
      biogenesis.
AB  - Bacterial neutral lipid inclusions are structurally related to eukaryotic lipid
      bodies. These lipid inclusions are composed of a matrix of triacylglycerols
      (TAGs) or wax esters surrounded by a monolayer of phospholipids. Whereas the
      monolayers of lipid bodies from animal and plant cells harbor specific classes of
      proteins which are involved in the structure of the inclusions and lipid
      homoestasis, no such proteins are known to be associated with bacterial lipid
      inclusions. The present study was undertaken to reveal whether the mammalian
      lipid body proteins perilipin A, adipose differentiation-related protein, and
      tail-interacting protein of 47 kDa (TIP47), which comprise the so called PAT
      family proteins, and the maize (Zea mays L.) oleosin are targeted to prokaryotic
      TAG bodies in vivo. When fused to enhanced green fluorescent protein, all
      proteins except the oleosin were mainly located at the surfaces of lipid
      inclusions when heterologously expressed in the recombinant actinomycetes
      Rhodococcus opacus PD630 and Mycobacterium smegmatis mc(2)155. A more detailed
      intracellular distribution analysis of TIP47 in recombinant R. opacus cells by
      immunocytochemical labeling of ultrathin cryosections and freeze fracture
      replicas revealed a substantial amount of TIP47 protein also pervading the cores
      of the inclusions. We discuss the impact of these results on the current model of
      lipid body biogenesis in prokaryotes.

PMID- 17021227
TI  - Natural genetic transformation: A novel tool for efficient genetic engineering of
      the dairy bacterium Streptococcus thermophilus.
AB  - Streptococcus thermophilus is widely used for the manufacture of yoghurt and
      Swiss or Italian-type cheeses. These products have a market value of
      approximately 40 billion dollars per year, making S. thermophilus a species that
      has major economic importance. Even though the fermentation properties of this
      bacterium have been gradually improved by classical methods, there is great
      potential for further improvement through genetic engineering. Due to the recent
      publication of three complete genome sequences, it is now possible to use a
      rational approach for designing S. thermophilus starter strains with improved
      properties. Progress in this field, however, is hampered by a lack of genetic
      tools. Therefore, we developed a system, based on natural transformation, which
      makes genetic manipulations in S. thermophilus easy, rapid, and highly efficient.
      The efficiency of this novel tool should make it possible to construct food-grade
      mutants of S. thermophilus, opening up exciting new possibilities that should
      benefit consumers as well as the dairy industry.

PMID- 17021228
TI  - Bdellovibrio predation in the presence of decoys: Three-way bacterial
      interactions revealed by mathematical and experimental analyses.
AB  - Bdellovibrio bacteriovorus is a small, gram-negative, motile bacterium that preys
      upon other gram-negative bacteria, including several known human pathogens. Its
      predation efficiency is usually studied in pure cultures containing solely B.
      bacteriovorus and a suitable prey. However, in natural environments, as well as
      in any possible biomedical uses as an antimicrobial, Bdellovibrio is predatory in
      the presence of diverse decoys, including live nonsusceptible bacteria,
      eukaryotic cells, and cell debris. Here we gathered and mathematically modeled
      data from three-member cultures containing predator, prey, and nonsusceptible
      bacterial decoys. Specifically, we studied the rate of predation of planktonic
      late-log-phase Escherichia coli S17-1 prey by B. bacteriovorus HD100, both in the
      presence and in the absence of Bacillus subtilis nonsporulating strain 671, which
      acted as a live bacterial decoy. Interestingly, we found that although addition
      of the live Bacillus decoy did decrease the rate of Bdellovibrio predation in
      liquid cultures, this addition also resulted in a partially compensatory
      enhancement of the availability of prey for predation. This effect resulted in a
      higher final yield of Bdellovibrio than would be predicted for a simple inert
      decoy. Our mathematical model accounts for both negative and positive effects of
      predator-prey-decoy interactions in the closed batch environment. In addition, it
      informs considerations for predator dosing in any future therapeutic applications
      and sheds some light on considerations for modeling the massively complex
      interactions of real mixed bacterial populations in nature.

PMID- 17021229
TI  - Host PGRP gene expression and bacterial release in endosymbiosis of the weevil
      Sitophilus zeamais.
AB  - Intracellular symbiosis (endosymbiosis) with gram-negative bacteria is common in
      insects, yet little is known about how the host immune system perceives the
      endosymbionts and controls their growth and invasion without complete bacterial
      clearance. In this study, we have explored the expression of a peptidoglycan
      recognition protein gene of the weevil Sitophilus zeamais (wPGRP); an ortholog in
      Drosophila (i.e., PGRP-LB) was recently shown to downregulate the Imd pathway (A.
      Zaidman-Remy, M. Herve, M. Poidevin, S. Pili-Floury, M. S. Kim, D. Blanot, B. H.
      Oh, R. Ueda, D. Mengin-Lecreulx, and B. Lemaitre, Immunity 24:463-473, 2006).
      Insect challenges with bacteria have demonstrated that wPGRP is induced by gram
      negative bacteria and that the level of induction depends on bacterial growth.
      Real-time reverse transcription-PCR quantification of the wPGRP gene transcript
      performed at different points in insect development has shown a high steady-state
      level in the bacteria-bearing organ (the bacteriome) of larvae and a high level
      of wPGRP up-regulation in the symbiotic nymphal phase. Concomitantly, during this
      stage fluorescence in situ hybridization has revealed an endosymbiont release
      from the host bacteriocytes. Together with the previously described high
      induction level of endosymbiont virulence genes at the nymphal phase (C. Dale, G.
      R. Plague, B. Wang, H. Ochman, and N. A. Moran, Proc. Natl. Acad. Sci. USA
      99:12397-12402, 2002), these findings indicate that insect mutualistic
      relationships evolve through an interplay between bacterial virulence and host
      immune defense and that the host immunity engages the PGRP gene family in that
      interplay.

PMID- 17021230
TI  - Introducing SONS, a tool for operational taxonomic unit-based comparisons of
      microbial community memberships and structures.
AB  - The recent advent of tools enabling statistical inferences to be drawn from
      comparisons of microbial communities has enabled the focus of microbial ecology
      to move from characterizing biodiversity to describing the distribution of that
      biodiversity. Although statistical tools have been developed to compare community
      structures across a phylogenetic tree, we lack tools to compare the memberships
      and structures of two communities at a particular operational taxonomic unit
      (OTU) definition. Furthermore, current tests of community structure do not
      indicate the similarity of the communities but only report the probability of a
      statistical hypothesis. Here we present a computer program, SONS, which
      implements nonparametric estimators for the fraction and richness of OTUs shared
      between two communities.

PMID- 17021231
TI  - Phylogenetic diversity, localization, and cell morphologies of members of the
      candidate phylum TG3 and a subphylum in the phylum Fibrobacteres, recently
      discovered bacterial groups dominant in termite guts.
AB  - Recently we discovered two novel, deeply branching lineages in the domain
      Bacteria from termite guts by PCR-based analyses of 16S rRNA (Y. Hongoh, P.
      Deevong, T. Inoue, S. Moriya, S. Trakulnaleamsai, M. Ohkuma, C. Vongkaluang, N.
      Noparatnaraporn, and T. Kudo, Appl. Environ. Microbiol. 71:6590-6599, 2005).
      Here, we report on the specific detection of these bacteria, the candidate phylum
      TG3 (Termite Group 3) and a subphylum in the phylum Fibrobacteres, by
      fluorescence in situ hybridization in the guts of the wood-feeding termites
      Microcerotermes sp. and Nasutitermes takasagoensis. Both bacterial groups were
      detected almost exclusively from the luminal fluid of the dilated portion in the
      hindgut. Each accounted for approximately 10% of the total prokaryotic cells,
      constituting the second-most dominant groups in the whole-gut microbiota. The
      detected cells of both groups were in undulate or vibroid forms and apparently
      resembled small spirochetes. The cell sizes were 0.2 to 0.4 by 1.3 to 6.0 microm
      and 0.2 to 0.3 by 1.3 to 4.9 microm in the TG3 and Fibrobacteres, respectively.
      Using PCR screenings with specific primers, we found that both groups are
      distributed among various termites. The obtained clones formed monophyletic
      clusters that were delineated by the host genus rather than by the geographic
      distance, implying a robust association between these bacteria and host termites.
      TG3 clones were also obtained from a cockroach gut, lake sediment, rice paddy
      soil, and deep-sea sediments. Our results suggest that the TG3 and Fibrobacteres
      bacteria are autochthonous gut symbionts of various termites and that the TG3
      members are also widely distributed among various other environments.

PMID- 17021232
TI  - Microbial community in black rust exposed to hot ridge flank crustal fluids.
AB  - During Integrated Ocean Drilling Program Expedition 301, we obtained a sample of
      black rust from a circulation obviation retrofit kit (CORK) observatory at a
      borehole on the eastern flank of Juan de Fuca Ridge. Due to overpressure, the
      CORK had failed to seal the borehole. Hot fluids from oceanic crust had
      discharged to the overlying bottom seawater and resulted in the formation of
      black rust analogous to a hydrothermal chimney deposit. Both culture-dependent
      and culture-independent analyses indicated that the black-rust-associated
      community differed from communities reported from other microbial habitats,
      including hydrothermal vents at seafloor spreading centers, while it shared
      phylotypes with communities previously detected in crustal fluids from the same
      borehole. The most frequently retrieved sequences of bacterial and archaeal 16S
      rRNA genes were related to the genera Ammonifex and Methanothermococcus,
      respectively. Most phylotypes, including phylotypes previously detected in
      crustal fluids, were isolated in pure culture, and their metabolic traits were
      determined. Quantification of the dissimilatory sulfite reductase (dsrAB) genes,
      together with stable sulfur isotopic and electron microscopic analyses, strongly
      suggested the prevalence of sulfate reduction, potentially by the Ammonifex group
      of bacteria. Stable carbon isotopic analyses suggested that the bulk of the
      microbial community was trophically reliant upon photosynthesis-derived organic
      matter. This report provides important insights into the phylogenetic,
      physiological, and trophic characteristics of subseafloor microbial ecosystems in
      warm ridge flank crusts.

PMID- 17021233
TI  - Applications of a rapid endospore viability assay for monitoring UV inactivation
      and characterizing arctic ice cores.
AB  - We have developed a rapid endospore viability assay (EVA) in which endospore
      germination serves as an indicator for viability and applied it to (i) monitor UV
      inactivation of endospores as a function of dose and (ii) determine the
      proportion of viable endospores in arctic ice cores (Greenland Ice Sheet Project
      2 [GISP2] cores; 94 m). EVA is based on the detection of dipicolinic acid (DPA),
      which is released from endospores during germination. DPA concentrations were
      determined using the terbium ion (Tb3+)-DPA luminescence assay, and germination
      was induced by L-alanine addition. The concentrations of germinable endospores
      were determined by comparison to a standard curve. Parallel EVA and phase
      contrast microscopy experiments to determine the percentage of germinable spores
      yielded comparable results (54.3% +/- 3.8% and 48.9% +/- 4.5%, respectively),
      while only 27.8% +/- 7.6% of spores produced CFU. EVA was applied to monitor the
      inactivation of spore suspensions as a function of UV dose, yielding reproducible
      correlations between EVA and CFU inactivation data. The 90% inactivation doses
      were 2,773 J/m2, 3,947 J/m2, and 1,322 J/m2 for EVA, phase-contrast microscopy,
      and CFU reduction, respectively. Finally, EVA was applied to quantify germinable
      and total endospore concentrations in two GISP2 ice cores. The first ice core
      contained 295 +/- 19 germinable spores/ml and 369 +/- 36 total spores/ml (i.e.,
      the percentage of germinable endospores was 79.9% +/- 9.3%), and the second core
      contained 131 +/- 4 germinable spores/ml and 162 +/- 17 total spores/ml (i.e.,
      the percentage of germinable endospores was 80.9% +/- 8.8%), whereas only 2
      CFU/ml were detected by culturing.

PMID- 17021234
TI  - Analysis of the collar-whisker structure of temperate lactococcal bacteriophage
      TP901-1.
AB  - Proteins homologous to the protein NPS (neck passage structure) are widespread
      among lactococcal phages. We investigated the hypothesis that NPS is involved in
      the infection of phage TP901-1 by analysis of an NPS- mutant. NPS was determined
      to form a collar-whisker complex but was shown to be nonessential for infection,
      phage assembly, and stability.

PMID- 17021235
TI  - Effect of octamethylcyclotetrasiloxane on methylation of bismuth by
      Methanosarcina barkeri.
AB  - Octamethylcyclotetrasiloxane (OMCTS), a common constituent of household products,
      triggers the transformation of bismuth to the volatile toxic derivative
      trimethylbismuth by Methanosarcina barkeri, which is a representative member of
      the sewage sludge microflora. Comparative studies with the ionophores monensin
      and lasalocid, which induce effects similar to those observed for OMCTS,
      indicated that the stimulation of bismuth methylation is not specific for the
      siloxane and suggested that the stimulation observed is mainly due to facilitated
      membrane permeation of the metal ion.

PMID- 17021236
TI  - Mycobacteria and fungi in moisture-damaged building materials.
AB  - In contrast to the growth of fungi, the growth of mycobacteria in moisture
      damaged building materials has rarely been studied. Environmental mycobacteria
      were isolated from 23% of samples of moisture-damaged materials (n = 88). The
      occurrence of mycobacteria increased with increasing concentrations of fungi.
      Mycobacteria may contribute to indoor exposure and associated adverse health
      effects.

PMID- 17021237
TI  - Endopeptidase and glycosidase activities of the bacteriophage B30 lysin.
AB  - Synthetic peptides corresponding to portions of group B streptococcal
      peptidoglycan were used to show that the endopeptidase activity of bacteriophage
      B30 lysin cleaves between D-Ala in the stem peptide and L-Ala in the cross bridge
      and that the minimal peptide sequence cleaved is DL-gamma-Glu-Lys-D-Ala-Ala-Ala.
      The only glycosidase activity present is that of N-acetyl-beta-D-muramidase.

PMID- 17021239
TI  - Establishment of a gene expression system in Ochrobactrum anthropi.
AB  - Genetic studies of Ochrobactrum anthropi are hindered by the lack of a suitable
      gene expression system. We constructed a set of vectors containing several
      promoters and a His tag fusion in the N terminus to facilitate protein detection
      and purification. The new vectors should significantly enhance the genetic
      manipulation and characterization of O. anthropi.

PMID- 17021238
TI  - Molecular evidence for the broad distribution of anaerobic ammonium-oxidizing
      bacteria in freshwater and marine sediments.
AB  - Previously available primer sets for detecting anaerobic ammonium-oxidizing
      (anammox) bacteria are inefficient, resulting in a very limited database of such
      sequences, which limits knowledge of their ecology. To overcome this limitation,
      we designed a new primer set that was 100% specific in the recovery of
      approximately 700-bp 16S rRNA gene sequences with >96% homology to the
      "Candidatus Scalindua" group of anammox bacteria, and we detected this group at
      all sites studied, including a variety of freshwater and marine sediments and
      permafrost soil. A second primer set was designed that exhibited greater
      efficiency than previous primers in recovering full-length (1,380-bp) sequences
      related to "Ca. Scalindua," "Candidatus Brocadia," and "Candidatus Kuenenia."
      This study provides evidence for the widespread distribution of anammox bacteria
      in that it detected closely related anammox 16S rRNA gene sequences in 11
      geographically and biogeochemically diverse freshwater and marine sediments.

PMID- 17021240
TI  - Phylogeny of acetate-utilizing microorganisms in soils along a nutrient gradient
      in the Florida Everglades.
AB  - The consumption of acetate in soils taken from a nutrient gradient in the
      northern Florida Everglades was studied by stable isotope probing. Bacterial and
      archaeal 16S rRNA gene clone libraries from eutrophic and oligotrophic soil
      microcosms strongly suggest that a significant amount of acetate is consumed by
      syntrophic acetate oxidation in nutrient-enriched soil.

PMID- 17021241
TI  - Whole-genome reciprocal BLAST analysis reveals that planctomycetes do not share
      an unusually large number of genes with Eukarya and Archaea.
AB  - The genome sequences of Rhodopirellula baltica, formerly Pirellula sp. strain 1,
      Blastopirellula marina, Gemmata obscuriglobus, and Kuenenia stuttgartiensis were
      used in a series of pairwise reciprocal best-hit analyses to evaluate the
      contested evolutionary position of Planctomycetes. Contrary to previous reports
      which suggested that R. baltica had a high percentage of genes with closest
      matches to Archaea and Eukarya, we show here that these Planctomycetes do not
      share an unusually large number of genes with the Archaea or Eukarya, compared
      with other Bacteria. Thus, best-hit analyses may assign phylogenetic affinities
      incorrectly if close relatives are absent from the sequence database.

PMID- 17021242
TI  - Abundance and population structure of ammonia-oxidizing bacteria that inhabit
      canal sediments receiving effluents from municipal wastewater treatment plants.
AB  - A polyphasic, culture-independent study was conducted to investigate the
      abundance and population structure of ammonia-oxidizing bacteria (AOB) in canal
      sediments receiving wastewater discharge. The abundance of AOB ranged from 0.2 to
      1.9% and 1.6 to 5.7% of the total bacterial fraction by real-time PCR and
      immunofluorescence staining, respectively. Clone analysis and restriction
      endonuclease analysis revealed that the AOB communities influenced by the
      wastewater discharge were dominated by Nitrosomonas, were similar to each other,
      and were less diverse than the communities outside of the immediate discharge
      zone.

PMID- 17021243
TI  - Caution on interpretation of legionella results obtained using real-time PCR for
      environmental water samples.

PMID- 17021244
TI  - Possible errors in the interpretation of ethidium bromide and PicoGreen DNA
      staining results from ethidium monoazide-treated DNA.

PMID- 17021245
TI  - Development of novel immunoglobulin G (IgG), IgA, and IgM enzyme immunoassays
      based on recombinant Puumala and Dobrava hantavirus nucleocapsid proteins.
AB  - Human infections with Asian and European hantaviruses can result in hemorrhagic
      fever with renal syndromes of differing severities characterized by renal
      dysfunction and sometimes by pulmonary symptoms. For the serological detection of
      human infections by hantaviruses relevant for Europe, we developed monoclonal
      antibody capture immunoglobulin G (IgG) and IgA enzyme-linked immunosorbent
      assays (ELISAs) based on yeast-expressed nucleocapsid proteins of Puumala and
      Dobrava hantaviruses. Moreover, for diagnosis of acute infections, mu-capture IgM
      ELISAs were established with nucleocapsid proteins expressed in Drosophila
      melanogaster Schneider S2 cells. The cutoff values of the ELISAs were determined
      by investigation of up to 500 human anti-hantavirus-negative serum samples. The
      specificities of the Puumala and Dobrava virus-specific IgM, IgA, and IgG ELISAs
      were found to be 100%. The sensitivities of these ELISAs were determined to be
      100% with panels of characterized anti-Puumala or anti-Dobrava virus-positive
      human serum samples. In most cases, Puumala and Dobrava virus infections could be
      differentiated by ELISA reactivity alone, i.e., endpoint titration with
      homologous and heterologous antigens.

PMID- 17021246
TI  - Antibodies specific for the high-molecular-weight adhesion proteins of
      nontypeable Haemophilus influenzae are opsonophagocytic for both homologous and
      heterologous strains.
AB  - The HMW1/HMW2-like adhesion proteins of nontypeable Haemophilus influenzae (NTHI)
      are expressed by 75% of NTHI strains. Antibodies directed against these proteins
      are opsonophagocytic in vitro and are protective in an animal model of infection.
      The objective of the present study was to determine the opsonophagocytic activity
      of high-titer anti-HMW1/HMW2 immune sera against both homologous and heterologous
      NTHI strains. Chinchillas were immunized with purified HMW1/HMW2-like proteins
      from five prototype NTHI strains. Serum opsonophagocytic activity was monitored
      in an assay that uses a human promyelocytic cell line, HL-60, as the source of
      phagocytic cells. Preimmune sera did not demonstrate opsonophagocytic killing of
      any strains. In contrast, the immune sera demonstrated killing of the five
      homologous NTHI strains at titers ranging from 1:320 to 1:640. The immune sera
      also demonstrated killing of eight heterologous NTHI strains that express
      HMW1/HMW2-like proteins at titers ranging from 0 to 1:640. Killing of
      heterologous strains sometimes demonstrated a prozone phenomenon. None of the
      immune sera killed NTHI strains that did not express HMW1/HMW2-like proteins.
      Adsorption of immune sera with HMW1/HMW2-like proteins purified from either
      homologous or heterologous NTHI strains eliminated opsonophagocytic killing of
      homologous strains in most cases. These data demonstrate that antibodies produced
      following immunization with the HMW1/HMW2-like proteins are opsonophagocytic for
      both homologous and heterologous NTHI and strongly suggest that common epitopes
      recognized by functionally active antibodies exist on the HMW1/HMW2-like proteins
      of unrelated NTHI strains. The results argue for the continued investigation of
      the HMW1/HMW2-like proteins as potential vaccine candidates for the prevention of
      NTHI disease.

PMID- 17021247
TI  - Use of the immunodominant 18-kiloDalton small heat shock protein as a serological
      marker for exposure to Mycobacterium ulcerans.
AB  - While it is well established that proximity to wetlands is a risk factor for
      contracting Buruli ulcer, it is not clear what proportion of a population living
      in an area where the etiologic agent, Mycobacterium ulcerans, is endemic is
      actually exposed to this disease. Immunological cross-reactivity among
      mycobacterial species complicates the development of a specific serological test.
      Among immunodominant proteins recognized by a panel of anti-M. ulcerans
      monoclonal antibodies, the M. ulcerans homologue of the M. leprae 18-kDa small
      heat shock protein (shsp) was identified. Since this shsp has no homologues in M.
      bovis and M. tuberculosis, we evaluated its use as a target antigen for a
      serological test. Anti-18-kDa shsp antibodies were frequently found in the sera
      of Buruli ulcer patients and of healthy household contacts but rarely found in
      controls from regions where the infection is not endemic. The results indicate
      that only a small proportion of M. ulcerans-infected individuals contract the
      clinical disease.

PMID- 17021248
TI  - Repression of human GSTA1 by interleukin-1beta is mediated by variant hepatic
      nuclear factor-1C.
AB  - Down-regulation of glutathione transferase A1 (GSTA1) expression has profound
      implications in cytoprotection against toxic by-products of lipid peroxidation
      produced during inflammation. We investigated the role of hepatic nuclear factor
      1 (HNF-1) in repression of human GSTA1 expression by interleukin (IL)-1beta in
      Caco-2 cells. In luciferase reporter assays, overexpression of HNF-1alpha
      increased GSTA1 transcriptional activity via an HNF-1 response element (HRE) in
      the proximal promoter. In addition, constitutive mRNA levels of GSTA1 and HNF
      1alpha rose concurrently in Caco-2 cells with increasing stage of confluence. IL
      1beta reduced GSTA1 mRNA levels at all stages of confluence; however, HNF-1alpha
      mRNA levels were not altered. IL-1beta repressed GSTA1 transcriptional activity,
      an effect that was abolished by mutating the HRE. Similar results were observed
      in HT-29 and HepG2 cells. Overexpression of HNF-1alpha did not counteract IL
      1beta-mediated repression of GSTA1 transcription either in reporter assays or at
      the mRNA level. Involvement of the transdominant repressor C isoform of variant
      HNF-1 (vHNF-1C) in GSTA1 repression was demonstrated, because vHNF-1C
      overexpression significantly reduced GSTA1 transcriptional activity. Finally, IL
      1beta caused concentration-related up-regulation of vHNF-1C mRNA levels and
      increased binding of vHNF-1C protein to the HRE, whereas HNF-1alpha-HRE complex
      formation was reduced. These findings indicate that IL-1beta represses GSTA1
      transcription via a mechanism involving overexpression of vHNF-1C.

PMID- 17021249
TI  - c-Abl kinase regulates curcumin-induced cell death through activation of c-Jun N
      terminal kinase.
AB  - Curcumin, a natural phenolic compound found in turmeric (Curcuma longa) exhibits
      anticancer properties, attributed to its antiproliferative and apoptosis-inducing
      activity. The ubiquitously expressed nonreceptor tyrosine kinase c-Abl regulates
      stress responses induced by oxidative agents such as ionizing radiation and H2O2.
      In this study, we show that c-Abl is an important component of the cell death
      response activated by curcumin and that Abl mediates this response partly through
      activation of c-Jun N-terminal kinase (JNK). Therefore, inhibition of Abl by
      STI571 [imatinib (Gleevec)] treatment or down-regulation of Abl expression
      through Abl-specific short-hairpin RNA (shRNA) diminished cell death induction
      and JNK activation. Highlighting the interdependent nature of the Abl and JNK
      signaling in the curcumin-induced cell death response, a JNK inhibitor
      [anthra(1,9-cd)pyrazol-6(2H)-one-1,9-pyrazoloanthrone (SP600125)] caused very
      little cell death inhibition in STI571-pretreated cells and in Abl shRNA
      expressing cells. Moreover, treatment with Abl and JNK inhibitor alone or
      together caused similar levels of cell death inhibition. Although p53 induction
      in response to curcumin treatment is dependent on Abl, we found that Abl-->p53
      signaling is not necessary for curcumin-induced cell death. Taken together, the
      results demonstrate the differential roles played by Abl-->p53 and Abl-->JNK
      signaling events in modulating the cell death response to curcumin.

PMID- 17021250
TI  - Atg22 recycles amino acids to link the degradative and recycling functions of
      autophagy.
AB  - In response to stress conditions (such as nutrient limitation or accumulation of
      damaged organelles) and certain pathological situations, eukaryotic cells use
      autophagy as a survival mechanism. During nutrient stress the main purpose of
      autophagy is to degrade cytoplasmic materials within the lysosome/vacuole lumen
      and generate an internal nutrient pool that is recycled back to the cytosol. This
      study elucidates a molecular mechanism for linking the degradative and recycling
      roles of autophagy. We show that in contrast to published studies, Atg22 is not
      directly required for the breakdown of autophagic bodies within the
      lysosome/vacuole. Instead, we demonstrate that Atg22, Avt3, and Avt4 are
      partially redundant vacuolar effluxers, which mediate the efflux of leucine and
      other amino acids resulting from autophagic degradation. The release of
      autophagic amino acids allows the maintenance of protein synthesis and viability
      during nitrogen starvation. We propose a "recycling" model that includes the
      efflux of macromolecules from the lysosome/vacuole as the final step of
      autophagy.

PMID- 17021251
TI  - PER1 is required for GPI-phospholipase A2 activity and involved in lipid
      remodeling of GPI-anchored proteins.
AB  - Glycosylphoshatidylinositol (GPI) anchors are remodeled during their transport to
      the cell surface. Newly synthesized proteins are transferred to a GPI anchor,
      consisting of diacylglycerol with conventional C16 and C18 fatty acids, whereas
      the lipid moiety in mature GPI-anchored proteins is exchanged to either
      diacylglycerol containing a C26:0 fatty acid in the sn-2 position or ceramide in
      Saccharomyces cerevisiae. Here, we report on PER1, a gene encoding a protein that
      is required for the GPI remodeling pathway. We found that GPI-anchored proteins
      could not associate with the detergent-resistant membranes in per1Delta cells. In
      addition, the mutant cells had a defect in the lipid remodeling from normal
      phosphatidylinositol (PI) to a C26 fatty acid-containing PI in the GPI anchor. In
      vitro analysis showed that PER1 is required for the production of lyso-GPI,
      suggesting that Per1p possesses or regulates the GPI-phospholipase A2 activity.
      We also found that human PERLD1 is a functional homologue of PER1. Our results
      demonstrate for the first time that PER1 encodes an evolutionary conserved
      component of the GPI anchor remodeling pathway, highlighting the close connection
      between the lipid remodeling of GPI and raft association of GPI-anchored
      proteins.

PMID- 17021252
TI  - A eukaryotic capsular polysaccharide is synthesized intracellularly and secreted
      via exocytosis.
AB  - Cryptococcus neoformans, which causes fatal infection in immunocompromised
      individuals, has an elaborate polysaccharide capsule surrounding its cell wall.
      The cryptococcal capsule is the major virulence factor of this fungal organism,
      but its biosynthetic pathways are virtually unknown. Extracellular
      polysaccharides of eukaryotes may be made at the cell membrane or within the
      secretory pathway. To test these possibilities for cryptococcal capsule
      synthesis, we generated a secretion mutant in C. neoformans by mutating a
      Sec4/Rab8 GTPase homolog. At a restrictive temperature, the mutant displayed
      reduced growth and protein secretion, and accumulated approximately 100-nm
      vesicles in a polarized manner. These vesicles were not endocytic, as shown by
      their continued accumulation in the absence of polymerized actin, and could be
      labeled with anti-capsular antibodies as visualized by immunoelectron microscopy.
      These results indicate that glucuronoxylomannan, the major cryptococcal capsule
      polysaccharide, is trafficked within post-Golgi secretory vesicles. This strongly
      supports the conclusion that cryptococcal capsule is synthesized intracellularly
      and secreted via exocytosis.

PMID- 17021253
TI  - Transition of galactosyltransferase 1 from trans-Golgi cisterna to the trans
      Golgi network is signal mediated.
AB  - The Golgi apparatus (GA) is the organelle where complex glycan formation takes
      place. In addition, it is a major sorting site for proteins destined for various
      subcellular compartments or for secretion. Here we investigate beta1,4
      galactosyltransferase 1 (galT) and alpha2,6-sialyltransferase 1 (siaT), two trans
      Golgi glycosyltransferases, with respect to their different pathways in monensin
      treated cells. Upon addition of monensin galT dissociates from siaT and the GA
      and accumulates in swollen vesicles derived from the trans-Golgi network (TGN),
      as shown by colocalization with TGN46, a specific TGN marker. We analyzed various
      chimeric constructs of galT and siaT by confocal fluorescence microscopy and time
      lapse videomicroscopy as well as Optiprep density gradient fractionation. We show
      that the first 13 amino acids of the cytoplasmic tail of galT are necessary for
      its localization to swollen vesicles induced by monensin. We also show that the
      monensin sensitivity resulting from the cytoplasmic tail can be conferred to
      siaT, which leads to the rapid accumulation of the galT-siaT chimera in swollen
      vesicles upon monensin treatment. On the basis of these data, we suggest that
      cycling between the trans-Golgi cisterna and the trans-Golgi network of galT is
      signal mediated.

PMID- 17021254
TI  - The WD repeat-containing protein IFTA-1 is required for retrograde intraflagellar
      transport.
AB  - The assembly and maintenance of cilia require intraflagellar transport (IFT), a
      microtubule-dependent bidirectional motility of multisubunit protein complexes
      along ciliary axonemes. Defects in IFT and the functions of motile or sensory
      cilia are associated with numerous human ailments, including polycystic kidney
      disease and Bardet-Biedl syndrome. Here, we identify a novel Caenorhabditis
      elegans IFT gene, IFT-associated gene 1 (ifta-1), which encodes a WD repeat
      containing protein with strong homology to a mammalian protein of unknown
      function. Both the C. elegans and human IFTA-1 proteins localize to the base of
      cilia, and in C. elegans, IFTA-1 can be observed to undergo IFT. IFTA-1 is
      required for the function and assembly of cilia, because a C. elegans ifta-1
      mutant displays chemosensory abnormalities and shortened cilia with prominent
      ciliary accumulations of core IFT machinery components that are indicative of
      retrograde transport defects. Analyses of C. elegans IFTA-1 localization/motility
      along bbs mutant cilia, where anterograde IFT assemblies are destabilized, and in
      a che-11 IFT gene mutant, demonstrate that IFTA-1 is closely associated with the
      IFT particle A subcomplex, which is implicated in retrograde IFT. Together, our
      data indicate that IFTA-1 is a novel IFT protein that is required for retrograde
      transport along ciliary axonemes.

PMID- 17021255
TI  - Staphylococcus aureus fibronectin binding protein-A induces motile attachment
      sites and complex actin remodeling in living endothelial cells.
AB  - Staphylococcus aureus fibronectin binding protein-A (FnBPA) stimulates
      alpha5beta1-integrin signaling and actin rearrangements in host cells. This
      eventually leads to invasion of the staphylococci and their targeting to
      lysosomes. Using live cell imaging, we found that FnBPA-expressing staphylococci
      induce formation of fibrillar adhesion-like attachment sites and translocate
      together with them on the surface of human endothelial cells (velocity
      approximately 50 microm/h). The translocating bacteria recruited cellular actin
      and Rab5 in a cyclic and alternating manner, suggesting unsuccessful attempts of
      phagocytosis by the endothelial cells. Translocation, actin recruitment, and
      eventual invasion of the staphylococci was regulated by the fibrillar adhesion
      protein tensin. The staphylococci also regularly produced Neural Wiskott-Aldrich
      syndrome protein-controlled actin comet tails that further propelled them on the
      cell surface (velocity up to 1000 microm/h). Thus, S. aureus FnBPA produces
      attachment sites that promote bacterial movements but subvert actin- and Rab5
      reorganization during invasion. This may constitute a novel strategy of S. aureus
      to postpone invasion until its toxins become effective.

PMID- 17021256
TI  - Noncore components of the fission yeast gamma-tubulin complex.
AB  - Relatively little is known about the in vivo function of individual components of
      the eukaryotic gamma-tubulin complex (gamma-TuC). We identified three genes,
      gfh1+, mod21+, and mod22+, in a screen for fission yeast mutants affecting
      microtubule organization. gfh1+ is a previously characterized gamma-TuC protein
      weakly similar to human gamma-TuC subunit GCP4, whereas mod21+ is novel and shows
      weak similarity to human gamma-TuC subunit GCP5. We show that mod21p is a bona
      fide gamma-TuC protein and that, like gfh1Delta mutants, mod21Delta mutants are
      viable. We find that gfh1Delta and mod21Delta mutants have qualitatively normal
      microtubule nucleation from all types of microtubule-organizing centers (MTOCs)
      in vivo but quantitatively reduced nucleation from interphase MTOCs, and this is
      exacerbated by mutations in mod22+. Simultaneous deletion of gfh1p, mod21p, and
      alp16p, a third nonessential gamma-TuC protein, does not lead to additive
      defects, suggesting that all three proteins contribute to a single function.
      Coimmunoprecipitation experiments suggest that gfh1p and alp16p are codependent
      for association with a small "core" gamma-TuC, whereas mod21p is more
      peripherally associated, and that gfh1p and mod21p may form a subcomplex
      independently of the small gamma-TuC. Interestingly, sucrose gradient analysis
      suggests that the major form of the gamma-TuC in fission yeast may be a small
      complex. We propose that gfh1p, mod21p, and alp16 act as facultative "noncore"
      components of the fission yeast gamma-TuC and enhance its microtubule-nucleating
      ability.

PMID- 17021257
TI  - Therapeutic potential of phosphatidylinositol 3-kinase inhibitors in inflammatory
      respiratory disease.
AB  - The phosphoinositide 3-kinase(s) (PI3K) are a family of proteins that catalyze
      the phosphorylation of the 3-OH position of phosphoinositides and generate lipids
      that control a wide variety of intracellular signaling pathways. They are
      classified into three families according to their structure and substrate
      specificity and are thought to have distinct biological roles. Recent studies
      suggested that numerous components of the PI3K pathway play a crucial role in the
      expression and activation of inflammatory mediators, inflammatory cell
      recruitment, immune cell function, airway remodeling, and corticosteroid
      insensitivity in chronic inflammatory respiratory disease. Selective PI3K
      inhibitors have been developed that reduce inflammation and some characteristics
      of disease in experimental animal models. Targeting specific PI3K isoforms that
      may be overexpressed or overactive in disease should allow for selective
      treatment of respiratory diseases. Encouraging data from animal models, primary
      cells and clinical studies in other diseases suggest that inhibitors of PI3K/Akt
      may prove to be useful novel therapies in the treatment of asthma and chronic
      obstructive pulmonary disease.

PMID- 17021258
TI  - Nicotinamide reverses neurological and neurovascular deficits in streptozotocin
      diabetic rats.
AB  - In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)
      is an important effector of oxidative-nitrosative injury, which contributes to
      the development of experimental diabetic peripheral neuropathy (DPN). However,
      the potential toxicity of complete PARP inhibition necessitates the utilization
      of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide
      (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can
      improve energy status and inhibit cell death in ischemic tissues. We report the
      dose-dependent effects of nicotinamide in an established model of early DPN.
      Control and streptozotocin-diabetic rats were treated with 200 to 400 mg/kg/day
      nicotinamide (i.p.) for 2 weeks after 2 weeks of untreated diabetes. Sciatic
      endoneurial nutritive blood flow was measured by microelectrode polarography and
      hydrogen clearance, and sciatic motor and hind-limb digital sensory nerve
      conduction velocities and thermal and mechanical algesia were measured by
      standard electrophysiological and behavioral tests. Malondialdehyde plus 4
      hydroxyalkenal concentration in the sciatic nerve and amino acid-(4)
      hydroxynonenal adduct and poly(ADP-ribosyl)ated protein expression in human
      Schwann cells were assessed by a colorimetric method with N-methyl-2-phenyl
      indole and Western blot analysis, respectively. Nicotinamide corrected increased
      sciatic nerve lipid peroxidation in concert with nerve perfusion deficits and
      dose-dependently attenuated nerve conduction slowing, as well as mechanical and
      thermal hyperalgesia. Nicotinamide (25 mM) prevented high (30 mM) glucose-induced
      overexpression of amino acid-(4)-hydroxynonenal adducts and poly(ADP-ribosyl)ated
      proteins in human Schwann cells. In conclusion, nicotinamide deserves
      consideration as an attractive, nontoxic therapy for the treatment of DPN.

PMID- 17021259
TI  - Group III metabotropic glutamate receptor agonists selectively suppress
      excitatory synaptic currents in the rat prefrontal cortex induced by 5
      hydroxytryptamine2A receptor activation.
AB  - Activation and blockade of prefrontal cortical 5-hydroxytryptamine2A (5-HT2A)
      receptors have been linked to the action of hallucinogenic and
      antidepressant/antipsychotic drugs; these effects may involve modulation of
      glutamate release from thalamocortical afferents. Although activation of
      metabotropic glutamate 2 (mGlu2) receptors may suppress 5-HT-induced excitatory
      postsynaptic currents (EPSCs), group III mGlu receptors (mGlu4/7/8) also are
      expressed in the thalamus and may suppress 5-HT-induced EPSCs. We have found by
      intracellular recordings from layer V pyramidal cells of the medial prefrontal
      cortex (mPFC) that group III mGlu receptor agonists (R,S)-4
      phosphonophenylglycine (PPG), L-4-phosphono-2-aminobutyric acid (L-AP4), L-serine
      O-phosphate (L-SOP), and (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4)
      preferentially suppress 5-HT-induced EPSCs compared with excitatory postsynaptic
      potentials evoked by electrical stimulation of the white matter. A number of
      pharmacological features [e.g., the rank order of agonist potency; MAP4 partial
      agonist action; differential potency for the group III mGlu receptor antagonist
      (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) in blocking the
      suppressant action of PPG or MAP4; and a relatively low potency of 2S-2-amino-2
      (1S,2S-2-carboxycycloprop-1-yl)-3(xanthy-9-yl)propanoic acid (LY341495) in
      blocking the suppressant action of PPG or L-SOP] suggest that activation of both
      mGlu4 and mGlu8 receptors may play a role in suppressing 5-HT-induced EPSCs.
      Furthermore, L-SOP did not alter the synaptic currents or steady-state inward
      current induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid.
      Thus, although both group III and group II mGlu receptor agonists suppress the
      frequency of 5-HT-induced EPSCs in the mPFC, they differ in that the group III
      mGlu receptor agonists appear to have relatively minimal effects on glutamate
      released by sources other than thalamocortical afferents.

PMID- 17021260
TI  - Inhibition of nicotine metabolism by methoxysalen: Pharmacokinetic and
      pharmacological studies in mice.
AB  - Studies were undertaken to examine whether methoxsalen (9-methoxyfuro[3,2
      g][1]benzopyran-7-one), a specific and relatively selective inhibitor of human
      CYP2A6, inhibited CYP2A5-mediated nicotine metabolism in vitro. Furthermore,
      studies were performed in vivo to determine whether methoxsalen would modulate
      acute nicotine pharmacokinetics and pharmacological effects (antinociception and
      hypothermia) in the ICR mouse. Our results demonstrated that methoxsalen
      competitively inhibits in vitro nicotine metabolism in mice. The inhibition was
      potent, as seen in human inhibition studies, with a Ki of 0.32 microM. In
      addition, we found that administration of methoxsalen significantly increased the
      plasma half-life of nicotine (approximately doubled) and increased its area under
      the curve compared with saline treatment. There was a dose-dependent enhancement
      in the pharmacological effects of nicotine (body temperature and analgesia) after
      methoxsalen treatment. Methoxsalen prolonged the duration of nicotine-induced
      antinociception and hypothermia (2.5 mg/kg) for periods up to 180 min
      postnicotine administration. Furthermore, this prolongation in nicotine's effects
      after methoxsalen was associated with a parallel prolongation of nicotine plasma
      levels in mice. These data strongly suggest that variation in the rates of
      nicotine metabolic inactivation substantially alter nicotine's pharmacological
      effects. In conclusion, these results confirmed that methoxsalen did indeed
      inhibit the conversion of nicotine to cotinine both in vitro and in vivo. They
      also suggest that mice may represent a suitable model for studying variation in
      nicotine metabolism and its impact on mechanisms of nicotine dependence,
      including the use of inhibitors to reduce nicotine metabolism.

PMID- 17021261
TI  - Sex differences in steroid modulation of ethanol withdrawal in male and female
      rats.
AB  - We investigated the actions of the neuroactive steroid, pregnanolone [corrected]
      and the ovarian steroid, 17beta-estradiol, on seizure expression during two time
      points of ethanol withdrawal (EW). Both steroids can exert rapid, nongenomic
      actions on the brain that include modulation of seizure activity. Because their
      basal levels differ in adult males and females and a major symptom of EW is
      increased seizure risk, we wanted to determine whether these steroids were
      anticonvulsant during EW. Rats were made ethanol-dependent by administration of
      6% ethanol in a nutritionally complete liquid diet for 14 days. After removal of
      the ethanol-containing diet, EW and paired control rats were tested at 1 or 3
      days for seizure responses to pentylenetetrazol. Consistent with previous
      reports, females seemed to have recovered from EW more quickly than males. We
      observed significant sex differences in responses to the steroids, primarily at 3
      days EW. Pregnanolone afforded protection against seizures with larger effects
      during EW than in control conditions and greater effects in female than male
      rats. In contrast, effects of estradiol were mixed. Some responses of
      ovariectomized female rats were similar to intact females, whereas other
      responses were more similar to males. Our behavioral findings are consistent with
      observed EW-induced changes in plasma corticosterone levels, showing persistent
      elevations in male but not female rats. These results support and extend earlier
      findings suggesting that although the hormonal milieu influences EW, innate
      differences in brain structure between the sexes also contribute to sex
      differences in EW.

PMID- 17021262
TI  - Anemia after kidney transplantation: time for action.

PMID- 17021263
TI  - ACE2: a new target for prevention of diabetic nephropathy?

PMID- 17021264
TI  - Who Wins the Competition: TRPV5 or Calbindin-D28K?

PMID- 17021265
TI  - Increased apoptosis in cystinotic fibroblasts and renal proximal tubule
      epithelial cells results from cysteinylation of protein kinase Cdelta.
AB  - Cystinosis is a rare genetic disease characterized by defective lysosomal cystine
      transport and increased lysosomal cystine. How lysosomal cystine causes the
      lethal nephropathic phenotype is unknown. It was shown recently that cultured
      fibroblasts and renal proximal tubule epithelial cells whose lysosomes are
      cystine-loaded display a two-fold or greater increase in apoptosis after both
      intrinsic and extrinsic stimuli. The mechanism for the increased apoptosis is
      unknown. Protein kinase Cdelta (PKCdelta) is a proapoptotic protein kinase that
      has been shown in vitro to be activated via cysteinylation. This report now shows
      that PKCdelta forms disulfide bonds specifically with cystine that is released
      from lysosomes in cultured fibroblasts and renal proximal tubule epithelial cells
      during apoptosis. PKCdelta in cystinotic fibroblasts and renal proximal tubule
      epithelial cells have a four- to six-fold greater association with its substrate,
      lamin B, and a 2.5-fold increase in specific activity after TNF-alpha exposure.
      Both RNA inhibition and chemical inhibition of PKCdelta resulted in a significant
      decrease in apoptosis in cystinotic cells but not in normal cells. It is proposed
      that abnormally increased apoptosis plays a role in evolution of the cystinotic
      phenotype.

PMID- 17021266
TI  - Glomerular localization and expression of Angiotensin-converting enzyme 2 and
      Angiotensin-converting enzyme: implications for albuminuria in diabetes.
AB  - Angiotensin-converting enzyme 2 (ACE2) expression has been shown to be altered in
      renal tubules from diabetic mice. This study examined the localization of ACE and
      ACE2 within the glomerulus of kidneys from control (db/m) and diabetic (db/db)
      mice and the effect of chronic pharmacologic ACE2 inhibition. ACE2 co-localized
      with glomerular epithelial cell (podocyte) markers, and its localization within
      the podocyte was confirmed by immunogold labeling. ACE, by contrast, was seen
      only in glomerular endothelial cells. By immunohistochemistry, in glomeruli from
      db/db mice, strong ACE staining was found more frequently than in control mice
      (db/db 64.6 +/- 6.3 versus db/m 17.8 +/- 3.4%; P < 0.005). By contrast, strong
      ACE2 staining in glomeruli from diabetic mice was less frequently seen than in
      controls (db/db 4.3 +/- 2.4 versus db/m 30.6 +/- 13.6%; P < 0.05). For
      investigation of the significance of reduced glomerular ACE2 expression, db/db
      mice were treated for 16 wk with a specific ACE2 inhibitor (MLN-4760) alone or
      combined with telmisartan, a specific angiotensin II type 1 receptor blocker. At
      the end of the study, glomerular staining for fibronectin, an extracellular
      matrix protein, was increased in both db/db and db/m mice that were treated with
      MLN-4760. Urinary albumin excretion (UAE) increased significantly in MLN-4760
      treated as compared with vehicle-treated db/db mice (743 +/- 200 versus 247 +/-
      53.9 microg albumin/mg creatinine, respectively; P < 0.05), and the concomitant
      administration of telmisartan completely prevented the increase in UAE associated
      with the ACE2 inhibitor (161 +/- 56; P < 0.05). It is concluded that ACE2 is
      localized in the podocyte and that in db/db mice glomerular expression of ACE2 is
      reduced whereas glomerular ACE expression is increased. The finding that chronic
      ACE2 inhibition increases UAE suggests that ACE2, likely by modulating the levels
      of glomerular angiotensin II via its degradation, may be a target for therapeutic
      interventions that aim to reduce albuminuria and glomerular injury.

PMID- 17021267
TI  - Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis
      patients with deranged nutritional status.
AB  - Decreased dietary protein intake and hemodialysis (HD)-associated protein
      catabolism predispose chronic HD (CHD) patients to deranged nutritional status,
      which is associated with poor clinical outcome in this population. Intradialytic
      parenteral nutrition (IDPN) reverses the net negative whole-body and skeletal
      muscle protein balance during HD. IDPN is costly and restricted by Medicare and
      other payers. Oral supplementation (PO) is a more promising, physiologic, and
      affordable intervention in CHD patients. Protein turnover studies were performed
      by primed-constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5))
      phenylalanine in eight CHD patients with deranged nutritional status before,
      during, and after HD on three separate occasions: (1) with IDPN infusion, (2)
      with PO administration, and (3) with no intervention (control). Results showed
      highly positive whole-body net balance during HD for both IDPN and PO (4.43 +/-
      0.7 and 5.71 +/- 1.2 mg/kg fat-free mass per min, respectively), compared with a
      neutral balance with control (0.25 +/- 0.5 mg/kg fat-free mass per min; P = 0.002
      and <0.001 for IDPN versus control and PO versus control, respectively). Skeletal
      muscle protein homeostasis during HD also improved with both IDPN and PO (50 +/-
      19 and 42 +/- 17 microg/100 ml per min) versus control (-27 +/- 13 microg/100 ml
      per min; P = 0.005 and 0.009 for IDPN versus control and PO versus control,
      respectively). PO resulted in persistent anabolic benefits in the post-HD phase
      for muscle protein metabolism, when anabolic benefits of IDPN dissipated (-53 +/-
      25 microg/100 ml per min for control, 47 +/- 41 microg/100 ml per min for PO [P =
      0.039 versus control], and -53 +/- 24 microg/100 ml per min for IDPN [P = 1.000
      versus control and 0.039 versus PO]). Long-term studies using intradialytic oral
      supplementation are needed for CHD patients with deranged nutritional status.

PMID- 17021268
TI  - Survival by dialysis modality in critically ill patients with acute kidney
      injury.
AB  - Among critically ill patients, acute kidney injury (AKI) requiring dialysis is
      associated with mortality rates generally in excess of 50%. Continuous renal
      replacement therapies (CRRT) often are recommended and widely used, although data
      to support its superiority over intermittent hemodialysis (IHD) are lacking. Data
      from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter
      observational study of AKI, were analyzed. Among 398 patients who required
      dialysis, the risk for death within 60 d was examined by assigned initial
      dialysis modality (CRRT [n = 206] versus IHD [n = 192]) using standard Kaplan
      Meier product limit estimates, proportional hazards ("Cox") regression methods,
      and a propensity score approach to account for selection effects. Crude survival
      rates were lower for patients who were treated with CRRT than IHD (survival at 30
      d 45 versus 58%; P = 0.006). Adjusted for age, hepatic failure, sepsis,
      thrombocytopenia, blood urea nitrogen, and serum creatinine and stratified by
      site, the relative risk for death associated with CRRT was 1.82 (95% confidence
      interval 1.26 to 2.62). Further adjustment for the propensity score did not
      materially alter the association (relative risk 1.92; 95% confidence interval
      1.28 to 2.89). Among critically ill patients with AKI, CRRT was associated with
      increased mortality. Although the results could reflect residual confounding by
      severity of illness, these data provide no evidence for a survival benefit
      afforded by CRRT. Larger, prospective, randomized clinical trials to compare CRRT
      and IHD in severe AKI are needed.

PMID- 17021269
TI  - Role of parathyroid hormone in the downregulation of liver cytochrome P450 in
      chronic renal failure.
AB  - Chronic renal failure (CRF) is associated with a decrease in drug metabolism
      secondary to a decrease in liver cytochrome P450 (P450). The predominant theory
      to explain this decrease is the presence of factors in the blood of uremic
      patients. This study tested the hypothesis that parathyroid hormone (PTH) could
      be this factor. The objectives of this study were to determine (1) the role of
      PTH in the downregulation of hepatocyte P450 induced by rat uremic serum, (2) the
      role of PTH in the downregulation of liver P450 in rats with CRF, and (3) the
      effects of PTH on P450 in hepatocytes. For this purpose, (1) hepatocytes were
      incubated with serum from rat with CRF that was depleted with anti-PTH antibodies
      or with serum from parathyroidectomized (CRF-PTX) rat with CRF, (2) the effect of
      PTX on liver P450 was evaluated in rats with CRF, and (3) the effects of PTH on
      P450 in hepatocytes were determined. The depletion of PTH from CRF serum
      completely reversed the downregulating effect of CRF serum on P450 in
      hepatocytes. Addition of PTH (10(-9) M) to depleted CRF serum induced a decrease
      in P450 similar to nondepleted CRF serum. The serum of CRF-PTX rats had no effect
      on P450 in hepatocytes compared with CRF serum. Adding PTH to CRF-PTX serum
      induced a similar decrease in P450 as obtained with CRF serum. Finally, PTX
      prevented the decrease of liver P450 in rats with CRF. In summary, PTH is the
      major mediator implicated in the downregulation of liver P450 in rats with CRF.

PMID- 17021270
TI  - Heat preconditioning attenuates renal injury in ischemic ARF in rats: role of
      heat-shock protein 70 on NF-kappaB-mediated inflammation and on tubular cell
      injury.
AB  - Although heat preconditioning has been known to be protective in various types of
      injury, the precise molecular mechanism for this is unclear. Recent observations
      that indicate that previous heat shock has an anti-inflammatory, antiapoptotic
      effect led to this investigation of the in vivo effect of heat preconditioning on
      NF-kappaB activation and inflammation and also on tubular cell injury in ischemic
      acute renal failure (ARF). Heat preconditioning provided marked functional
      protection and also reduced histologic evidence of tubular necrosis.
      Ischemia/reperfusion-induced NF-kappaB activation was suppressed by heat
      preconditioning with a subsequent decrease in monocyte chemoattractant protein-1
      expression and inflammatory cell infiltration. Heat preconditioning also
      suppressed the accumulation of phosphorylated inhibitory kappaBalpha
      (IkappaBalpha) with a resultant depletion of cytoplasmic IkappaBalpha, indicating
      that heat preconditioning blocked the activation of the IkappaB kinase complex.
      Tubular cell apoptosis, determined by terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling staining, also was decreased by heat
      preconditioning, and this was accompanied by decreased caspase 3 activation.
      Among several heat-shock proteins (HSP), HSP-70 was induced primarily by heat
      preconditioning. Inhibition of HSP-70 by quercetin almost completely reversed the
      functional protection that was provided by heat preconditioning. These data
      provide evidence that HSP-70 affords protection via inhibition of NF-kappaB
      mediated inflammation and also inhibition of the cell death pathway in ischemic
      ARF. Further elucidation of the cytoprotective mechanism of stress proteins could
      facilitate new target or drug development in the treatment of ARF.

PMID- 17021271
TI  - EUROCARE study underestimated the curability of breast cancer in Poland.

PMID- 17021272
TI  - A hitherto unreported high incidence of zoledronic acid-induced acute phase
      reaction in patients with cancer treatment-induced bone loss.

PMID- 17021273
TI  - Skill improvement among coalition members in the California Healthy Cities and
      Communities Program.
AB  - Community-driven, collaborative approaches to health promotion have the potential
      to enhance skills among community members and, in turn, increase community
      capacity. This study uses data from an evaluation of the California Healthy
      Cities and Communities (CHCC) Program to examine whether, and how, community
      problem-solving and collaboration skills are improved among coalition members and
      local coordinators in 20 participating communities. Methods include semi
      structured interviews with coordinators and mailed surveys with coalition members
      (n=330 in planning phase and n=243 in implementation phase). The largest number
      of coordinators reported skill improvement in defining health broadly and
      assessing needs and assets. Similarly, coalition members reported greatest skill
      improvement for defining health broadly, assessing needs and assets and setting
      priorities and developing action plans. Modest correlations were observed between
      number of roles played in the local healthy cities and communities project and
      each skill area assessed. Time committed to the local CHCC coalition and its
      activities was not meaningfully correlated with any of the skills. Types of skill
      building opportunities may be more important than number of hours devoted to
      meetings and activities in strengthening community problem-solving and
      collaboration skills among coalition members.

PMID- 17021274
TI  - Silicosis in Turkish denim sandblasters.
AB  - BACKGROUND: Sandblasting of jeans in small Turkish workshops has recently been
      recognized as a cause of silicosis. CASE SERIES: Between August 2004 and March
      2006, we admitted 16 young men with a history of working in small workplaces
      producing sandblasted jeans. Of these, 14 presented with respiratory symptoms and
      the remaining two through awareness of their work colleagues. In the first two
      cases, open-lung biopsy was required to confirm the diagnosis of silicosis. Later
      cases were diagnosed through a combination of their work history and the clinical
      and radiological findings. The mean age at presentation was 23 years with mean
      duration of employment as a sandblaster being 3 years. The first two cases died
      and the remainder, except two, are still receiving treatment. CONCLUSION: The
      production of sandblasted jeans in small uncontrolled workplaces may entail
      significant exposure to silica and the development of rapidly fatal silicosis.
      Urgent action is required to prevent further cases and mortality.

PMID- 17021275
TI  - Functional interaction between matrix metalloproteinase-3 and semaphorin-3C
      during cortical axonal growth and guidance.
AB  - In the developing cortex, axons and dendrites extend progressively in response to
      environmental cues attracting or repelling growing processes. Recent evidence
      suggests the existence of a functional link between guidance molecules and
      metalloproteinases. Here, we analyzed the putative functional interaction of
      matrix metalloproteinases (MMPs) with guidance cues of the semaphorin family
      during growth and guidance of cortical axons. Our results demonstrate that the
      expression pattern and the proteolytic activity of MMP-3 are consistent with a
      role of this particular MMP during cortical axon outgrowth. We found that MMP-3
      is required for an optimal axon extension and is involved in the Sema3C-dependent
      chemoattraction of cortical axons by modulating both the growth capacity and the
      orientation of growth. Interestingly, the inhibitory Sema3A decreased both the
      expression and activity of MMP-3. Taken together, our results reveal a molecular
      interaction between MMPs and semaphorins providing new insight into the molecular
      mechanism allowing axonal growth cone to respond to environmental guidance cues
      in the context of cortical development.

PMID- 17021276
TI  - Selective constraints on codon usage of nuclear genes from Arabidopsis thaliana.
AB  - Highly expressed nuclear genes from Arabidopsis thaliana show an increased
      frequency of codons that match abundant tRNAs, and it has been suggested that
      this reflects a selective pressure to increase translation efficiency. Here we
      explore the possibility that the difference in codon usage between highly
      expressed genes and other Arabidopsis genes is not the result of selection but,
      rather, arises from mutation biases. Specifically, we explore the possibility
      that an influence of transcription level on mutational properties coupled with a
      context dependency of mutations, both of which have been observed in various
      organisms, contribute to variation in codon-usage bias across genes. Using
      noncoding sites immediately flanking both high- and low-expression-coding
      sequences to infer context-dependent composition biases, we analyze codon-usage
      bias across genes. The data show that mutation bias cannot explain codon usage of
      high-expression genes in Arabidopsis and, surprisingly, also indicate that even
      low-expression genes are under selective constraints. In addition, the data
      indicate that the general preference for certain codons is context dependent; the
      composition of the 3' nucleotide, that is, the first position of the next codon,
      is correlated with what codon is found at an increased frequency in highly
      expressed genes. This context dependency indicates that selective pressure on
      codon usage is more complex than previously thought. Overall, the study supports
      previous suggestions that selection plays a significant role in determining codon
      usage of nuclear genes in A. thaliana.

PMID- 17021277
TI  - Estimating and modeling the cure fraction in population-based cancer survival
      analysis.
AB  - In population-based cancer studies, cure is said to occur when the mortality
      (hazard) rate in the diseased group of individuals returns to the same level as
      that expected in the general population. The cure fraction (the proportion of
      patients cured of disease) is of interest to patients and is a useful measure to
      monitor trends in survival of curable disease. There are 2 main types of cure
      fraction model, the mixture cure fraction model and the non-mixture cure fraction
      model, with most previous work concentrating on the mixture cure fraction model.
      In this paper, we extend the parametric non-mixture cure fraction model to
      incorporate background mortality, thus providing estimates of the cure fraction
      in population-based cancer studies. We compare the estimates of relative survival
      and the cure fraction between the 2 types of model and also investigate the
      importance of modeling the ancillary parameters in the selected parametric
      distribution for both types of model.

PMID- 17021278
TI  - Cancer outlier differential gene expression detection.
AB  - We study statistical methods to detect cancer genes that are over- or down
      expressed in some but not all samples in a disease group. This has proven useful
      in cancer studies where oncogenes are activated only in a small subset of
      samples. We propose the outlier robust t-statistic (ORT), which is intuitively
      motivated from the t-statistic, the most commonly used differential gene
      expression detection method. Using real and simulation studies, we compare the
      ORT to the recently proposed cancer outlier profile analysis (Tomlins and others,
      2005) and the outlier sum statistic of Tibshirani and Hastie (2006). The proposed
      method often has more detection power and smaller false discovery rates.
      Supplementary information can be found at
      http://www.biostat.umn.edu/~baolin/research/ort.html.

PMID- 17021279
TI  - Academic landscapes: one futuristic perspective.

PMID- 17021280
TI  - A special care dentistry specialty: sounds good, but . . .

PMID- 17021281
TI  - Dental student enrollment and graduation: a report by state, census division, and
      region.
AB  - The purpose of this study is to provide descriptive data on the presence of
      dental schools, dental school graduates, instate enrollment, and interstate
      dental education agreements for U.S. states, districts, and regions. This
      information may be helpful in deciding to open or maintain a dental school. Data
      from the American Dental Association (ADA), American Dental Education Association
      (ADEA), and U.S. Census Bureau were used to conduct cross-sectional comparisons
      for states, census divisions, and regions for 2000. In 2000, there were fifty
      four dental schools in thirty-two states and the District of Columbia. Total
      graduation across 1990-2000 was 43,289 dentists. Over half (56 percent) of the
      graduates were from public schools. The distribution of schools and graduates
      differed by geographic region. Alaska, Utah, Hawaii, and Nebraska were outliers
      with respect to high and low numbers of dental schools in states, in-state
      enrollment, and dentists to population. U.S. states, districts, and regions vary
      widely on the number of dental schools, dentists to population, first-year dental
      school enrollees, and dental school graduates. Further assessment on additional
      factors such as dental health provider shortage areas, state oral health status,
      and attractiveness of locations to dentists is needed to more fully understand
      the impact of these factors.

PMID- 17021282
TI  - How do social-psychological concerns impede the delivery of care to people with
      HIV? Issues for dental education.
AB  - Oral health is an essential aspect of the overall medical care for patients with
      HIV. However, fear of status disclosure is a significant barrier to access to
      care. Preparing future oral health care providers to maintain all aspects of
      confidentiality and to understand the role stigma plays in the lives of HIV
      positive individuals are critical issues that must be addressed by dental
      education. To provide important perspectives regarding HIV-related stigma and
      confidentiality, data from the HAART (Highly Active Antiretroviral Therapy)
      Project is presented. This study is a five-year National Institute of Allergy and
      Infectious Disease (NIAID)-funded longitudinal qualitative study of sero-positive
      African Americans' adherence to antiretroviral therapy (N=137). The current
      literature regarding HIV patient confidentiality and student attitudes regarding
      HIV/AIDS is also reviewed. Findings suggest that dental student attitudes may be
      improved by providing more comprehensive experiences and information and that
      procedures in place in dental clinics should be continuously monitored to ensure
      that patient confidentiality is maintained. Strategies for addressing these
      important issues in dental education are presented. Ensuring that dental school
      graduates are well prepared to maintain confidentiality with sensitivity to the
      role stigma plays in HIV disease has the potential to enhance access to health
      care.

PMID- 17021283
TI  - Nonacademic characteristics of dental school applicants.
AB  - The purpose of this study was to characterize the average dental school
      applicant's participation in four nonacademic areas: shadowing, extracurricular
      activities, volunteer experiences, and research. Demographic, academic, and
      nonacademic information was compared for 12 percent of all applicants to U.S.
      dental schools in 2005. Applicants had an average GPA of 3.23 and DAT Academic
      Average of 18.6. Applicants participated in an average of 3.7 extracurricular
      activities, 3.2 volunteer experiences, and 0.8 research projects. The average
      nondental employee applicant shadowed 172 hours. As shadowing hours increased,
      GPA declined. While academically similar, women reported significantly greater
      (p<.05) participation in all four nonacademic areas than males. Overall, Hispanic
      students reported the most shadowing hours and had the greatest percentage of
      parents as dentists, while black students had the least in both areas. Black
      students reported the most extracurricular activities. More than 90 percent of
      all applicants participated in three or four of the major nonacademic areas.
      Participation in extracurricular activities, volunteer experiences, and research
      projects was correlated; however, there was no relationship between shadowing
      hours and the other areas. Applicants with the most shadowing tended to be less
      academically qualified. The typical applicant reported a total of approximately
      eight extracurricular, volunteer, and research endeavors and 170 or more hours of
      shadowing. Results of this study can assist dental admissions committees in
      making qualitative comparisons between applicants with similar academic
      qualifications and aid health career counselors in advising predental students.

PMID- 17021284
TI  - Dental students' knowledge about careers in academic dentistry.
AB  - The purposes of this study were to determine the knowledge of fourth-year dental
      students regarding certain issues related to an academic career and to ascertain
      their intent to pursue such a career. Factors contributing to the students'
      intent to pursue academia were assessed, including the effect of dental school
      programs designed to educate students about a career in dental education. Surveys
      were sent to twelve U.S. dental schools that reported having either a mandatory
      or elective academic career educational program or no program at all. The surveys
      were completed by fourth-year dental students who were queried as to their
      knowledge of selected academic issues. Surveys were returned by 561 students from
      eleven of the twelve selected dental schools. Knowledge level of academic issues
      among respondents was overwhelmingly low. Factors contributing to the intent to
      pursue some form of faculty career were gender, plans to specialize, knowledge of
      academic issues, having a parent in higher education, and personal teaching
      experience. The results of this study suggest that dental students in general do
      not possess the knowledge and information necessary to make an informed decision
      regarding a career in dental education.

PMID- 17021285
TI  - Radiographs associated with one episode of orthodontic therapy.
AB  - Obtaining lifetime diagnostic radiation histories in head and neck cancer studies
      is often challenging due to the almost universal lack of centralized registries
      on X-ray utilization in medicine and dentistry. Both the common nature of
      orthodontics and the young age at which orthodontics typically occurs make it
      important to quantify what diagnostic radiographs are typically taken during
      orthodontic therapy. The aim of this study was to assess the number and type of
      radiographic films associated with one episode of orthodontic therapy in an
      educational setting. Charts stored in an orthodontic clinic at one academic
      setting were randomly sampled, and the type and number of radiographic
      examinations were tallied for the 325 individuals who were in orthodontic therapy
      for at least one year. Being under orthodontic therapy for one or more years was
      associated with a median number of seven extra-oral radiographs and twenty-four
      intra-oral radiographic films. The extra-oral radiographs included three
      panoramic radiographs and three cephalometric radiographs. Less than 10 percent
      of the variability was explained by factors such as age, gender, calendar year,
      surgical orthodontic therapy, and duration of therapy. Head and neck cancer
      etiology studies should take into account the ionizing radiation during episodes
      of orthodontic care. The substantial variability in radiographic practices in
      orthodontics could be reduced by research into clinical utility and by
      establishing guidelines.

PMID- 17021286
TI  - Increasing dentists' capacity for secondary prevention of eating disorders:
      identification of training, network, and professional contingencies.
AB  - The incidence of eating disorders has increased substantially over the last forty
      years. Primary care physicians and dentists share a parallel challenge for
      secondary prevention of anorexia nervosa and bulimia nervosa. The dentist, in
      particular, has a uniquely important and valuable role with respect to assessment
      of oral and physical manifestations, patient communication, referral, case
      management, and restorative care. Despite this crucial role, few dentists are
      engaged in eating disorder-specific secondary prevention. The purpose of this
      study was to explore beliefs, attitudes, and experiences of general dentists
      regarding eating disorder-specific secondary prevention behaviors using focus
      group methodology. Three ninety-minute focus groups were conducted with twenty
      one general dentists (seventeen male, four female) recruited from the 2004
      Academy of General Dentistry Leadership Conference. Data from the focus groups
      were analyzed to identify two over-arching themes and associated subthemes with
      regard to supports and barriers to eating disorder-specific secondary prevention
      practices. Analysis of data revealed that training, network, and dental
      professional contingencies emerged as places of influence for increasing capacity
      among dentists with regard to secondary prevention of eating disorders. This
      exploratory assessment identifies leverage points where strategic interventions
      including curriculum development, policies, and practices can be developed to
      support and sustain secondary preventive clinical behaviors among dentists.

PMID- 17021287
TI  - Competencies for the beginning dental practitioner in Canada: a validity survey.
AB  - As part of the recommended review of the national competencies for beginning
      general dentists in Canada, a validation survey was distributed to 731 dentists.
      The survey asked participants to supply demographic information and rate each of
      the forty-six competencies on a 5-point Likert scale. The response rate was 43.1
      percent (315 total usable responses). Self-reported demographic data was used to
      create respondent subgroups. The participants rated all of the competencies quite
      high with thirty-six of the forty-six receiving rankings averaging 4.0 or higher
      on the 5-point scale. No competency received a ranking averaging lower than 3.0.
      Competencies rated as most important by the entire sample were also rated as most
      important by all respondent subgroups. The results of this validation survey
      provide evidence of content validity and reinforce the value of a national
      competency document that can serve as a reference for curriculum management,
      program accreditation, and development of certification examinations.

PMID- 17021288
TI  - Student occupational exposure incidence: perception versus reality.
AB  - Reports of clinical injuries made to a dental school Office of Occupational
      Health and Safety at the time of their occurrence were compared to self-reports
      on a survey for dental students in five classes at various times over their
      educational careers. The majority of injuries were from needlesticks and mishaps
      with hand instruments. Underreporting at the time of injury was approximately one
      third in the first clinical year and one-half in the final clinical year of the
      three-year program. Students reported a greater perceived likelihood of injury
      later in their education than at the beginning but a decreased fear of such
      injuries. Female students reported more needlesticks and a greater fear of injury
      than did male students. It is hypothesized that a personal interpretation of the
      meaning of clinical injuries influences reporting behavior.

PMID- 17021289
TI  - Injury reports in a dental school: a two-year overview.
AB  - As teaching institutions, it is vital for dental schools to collect data on
      accidental injuries to identify potential problems, improve the quality of care
      of patients, and educate future practitioners about risk management. Our data
      reveal important trends concerning such injuries. These data were compiled over a
      two-year period (2001-03) from accident reports at one dental school. We
      categorized the accidents as follows: source (instrument causing the injury),
      recipient of injury, time of day, location within the dental school where the
      injury occurred, and body part injured. The population examined in this study
      consisted of predoctoral and postdoctoral dental students, staff, faculty, and
      patients of the dental school. The majority of injuries occurred in the
      predoctoral clinic toward the middle to the end of the scheduled clinic periods.
      The instrument most likely involved was a needle, and the body part most commonly
      injured was a finger. The collection and analysis of injury data may be used to
      identify trends that will aid in the prediction and prevention of these injuries
      and, at a national level, serve as a benchmark that other dental schools can
      employ to assess their relative frequency of injury.

PMID- 17021290
TI  - Survival analysis of complete veneer crowns vs. multisurface restorations: a
      dental school patient population.
AB  - The purpose of this study was to compare the longevity of crowns versus large
      multisurface restorations in posterior teeth. The investigation used the
      treatment database at Virginia Commonwealth University School of Dentistry. The
      inclusion criteria for the final data set used for analysis were: only one
      restored tooth per patient, premolars with three or more restored surfaces,
      molars with four or more restored surfaces, molars and premolars restored with
      complete veneer metal crowns, or crowns veneered with metal and porcelain. The
      Kaplan-Meier approach was used to visualize the survival curves, and the Cox
      proportional hazards model was used for analysis of predictor variables. The
      investigation indicates crowns survive longer than large restorations and
      premolar restorations survive longer than molar restorations. The median survival
      for crowns exceeded 16.6 years, with the median survival of premolar restorations
      being 4.4 years and molar restorations 1.3 years. An interaction between age and
      treatment was discovered, with overall survival decreasing as patient age
      increases. The doctor supervising the treatment also affected survival with
      treatment supervised by specialists lasting longer than treatment supervised by
      nonspecialists.

PMID- 17021291
TI  - An NHS at the mercy of freakonomics.

PMID- 17021292
TI  - The alienating language of health care.

PMID- 17021294
TI  - Response to 'Lapses at the NEJM'.

PMID- 17021295
TI  - Patients, clients or just people?

PMID- 17021296
TI  - Measuring healthcare outcomes--a race to utopia?

PMID- 17021297
TI  - Performance pay remuneration for consultants in the NHS: is the current system
      fair and fit for purpose?

PMID- 17021298
TI  - Assuming the mantle: the balancing act facing the new WHO Director-General.

PMID- 17021299
TI  - The Global Fund at five: what next for universal access for HIV/AIDS, TB and
      malaria?

PMID- 17021300
TI  - Meckel's diverticulum: a systematic review.
AB  - Meckel's diverticulum is the most common congenital malformation of
      gastrointestinal tract. It can cause complications in the form of ulceration,
      haemorrhage, intussusception, intestinal obstruction, perforation and, very
      rarely, vesicodiverticular fistulae and tumours. These complications, especially
      bleeding, are more common in the paediatric age group than in adults; however it
      is not uncommon to miss the diagnosis of Meckel's diverticulum in adults. Here,
      we reviewed the literature regarding the complications of this forgotten clinical
      entity in adults with potential diagnostic difficulties and management
      strategies.

PMID- 17021302
TI  - Appraisal, assessment and career development for doctors in training: the Mersey
      Deanery personal development portfolio.
AB  - OBJECTIVES: To develop a robust valid and exportable appraisal and assessment
      process for doctors in training which is portfolio based and works at all
      hospitals within the deanery. It is called the personal development portfolio.
      DESIGN: For every senior house officer, there was a recorded meeting with his or
      her supervisor, at the beginning, midterm and at the end of the post. An outside
      assessor witnessed the exit assessment meeting. SETTING: The Wirral Hospital, a
      District General Hospital with 72 senior house officers in 10 different
      specialties was used as a pilot site to develop the process. Then the process was
      exported and implemented at the other 12 trusts of the deanery. MAIN OUTCOME
      MEASURES: Records were kept of the induction, midterm and exit assessment
      meetings. A record was kept of the number of senior house officers succeeding and
      failing at their exit assessments. Also, the number promoted to the specialist
      registrar grade was recorded. RESULTS: The process was performed every 6 months
      on 11 occasions between 2000 and 2005. It involved 72 senior house officers in 10
      different specialties. On each occasion, participation usually exceeded 70%: 623
      were appraised and assessed and 609 of them (97.8%) had satisfactory exit
      assessments. For 14 doctors (2.2%), the process identified a cause for concern,
      which was usually accepted by the doctor and sometimes allowed remedial action to
      be taken. Twenty-six (4.2%) were promoted to the specialist registrar grade in
      this period. The process also identified the strengths and weaknesses of the
      senior house officer posts in the 10 different specialties that had such posts,
      and was used to encourage good medical teaching practice in them. Over 4 years,
      we exported the process to all the other 12 Trusts in the Mersey Deanery. Once
      established, the process was easy to use for both trainees and trainers, although
      it was time consuming. CONCLUSIONS: It was possible to develop and implement a
      portfolio based appraisal and assessment process, which was accepted by senior
      house officers and their trainers in all specialties at all hospitals within the
      deanery. Now that the senior house officer grade has been superseded by the
      Foundation and the training grade years, the principles of the personal
      development portfolio are being used to appraise and assess doctors in these
      grades too.

PMID- 17021303
TI  - A young stroke: the need for vigilance.

PMID- 17021301
TI  - Interventions for the treatment, management and rehabilitation of patients with
      chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review.
AB  - OBJECTIVES: To determine whether any particular intervention or combination of
      interventions is effective in the treatment, management and rehabilitation of
      adults and children with a diagnosis of chronic fatigue syndrome / myalgic
      encephalomyelitis (CFS/ME). DESIGN: Substantive update of a systematic review
      published in 2002. Randomized (RCTs) and non-randomized controlled trials of any
      intervention or combination of interventions were eligible for inclusion. Study
      participants could be adults or children with a diagnosis of CFS/ME based on any
      criteria. We searched eleven electronic databases, reference lists of articles
      and reviews, and textbooks on CFS/ME. Additional references were sought by
      contact with experts. RESULTS: Seventy studies met the inclusion criteria.
      Studies on behavioural, immunological, pharmacological and complementary
      therapies, nutritional supplements and miscellaneous other interventions were
      identified. Graded exercise therapy and cognitive behaviour therapy appeared to
      reduce symptoms and improve function based on evidence from RCTs. For most other
      interventions, evidence of effectiveness was inconclusive and some interventions
      were associated with significant adverse effects. CONCLUSIONS: Over the last five
      years, there has been a marked increase in the size and quality of the evidence
      base on interventions for CFS/ME. Some behavioural interventions have shown
      promising results in reducing the symptoms of CFS/ME and improving physical
      functioning. There is a need for research to define the characteristics of
      patients who would benefit from specific interventions and to develop clinically
      relevant objective outcome measures.

PMID- 17021304
TI  - The MRC randomized trial of streptomycin and its legacy: a view from the clinical
      front line.

PMID- 17021305
TI  - Philip Montagu D'arcy Hart (1900-2006).

PMID- 17021306
TI  - Curb your enthusiasm: undignified examinations.

PMID- 17021307
TI  - Tuberculosis in humans and animals: are we a threat to each other?

PMID- 17021308
TI  - Varying response to escalating the dose of imatinib in patients with CML who
      "acquire" a BCR-ABL M244V mutant allele.

PMID- 17021309
TI  - High-throughput screening of RNA polymerase inhibitors using a fluorescent UTP
      analog.
AB  - RNA polymerase (RNAP) is a well-validated target for the development of
      antibacterial and antituberculosis agents. Because the purification of large
      quantities of native RNA polymerase from pathogenic mycobacteria is hazardous and
      cumbersome, the primary screening was carried out using Escherichia coli RNAP.
      The authors have developed a high-throughput screening (HTS) assay to screen for
      novel inhibitors of RNAP. In this assay, a fluorescent analog of UTP, gamma-amino
      naphthalene sulfonic acid (gamma-AmNS) UTP, was used as one of the nucleotide
      substrates. Incorporation of UMP in RNA results in the release of gamma-AmNS-PPi,
      which has higher intrinsic fluorescence than (gamma-AmNS) UTP. The assay was
      optimized in a 384-well format and used to screen 670,000 compounds at a
      concentration of 10 microM. About 0.1% of the compounds showed more than 60%
      inhibition in the primary HTS. All the primary actives tested for dose response
      using the same assay had an EC(50) below 100 microM. Eighty percent of the
      primary HTS actives obtained using E. coli RNAP showed comparable activity
      against Mycobacterium smegmatis RNAP in the conventional radioactive assay.
      Activity of hits selected for the hit-to-lead optimization was also confirmed
      against Mycobacterium bovis RNAP which has >99% sequence identity with
      Mycobacterium tuberculosis RNAP subunits.

PMID- 17021310
TI  - Posterolateral knee reconstruction with an anatomical bone-patellar tendon-bone
      reconstruction of the fibular collateral ligament.
AB  - BACKGROUND: The authors have long advocated a graft reconstruction of the fibular
      collateral ligament, believing that direct suture repair or augmentation
      procedures do not provide a stable construct. PURPOSE: To describe an operative
      technique and determine the clinical outcome of a bone-patellar tendon-bone graft
      anatomical replacement of the fibular collateral ligament in a consecutive series
      of knees. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A consecutive
      group of knees undergoing anatomical posterolateral reconstruction that included
      a fibular collateral ligament reconstruction with a bone-patellar tendon-bone
      graft was prospectively followed to determine the functional outcome and failure
      rate. Thirteen patients (14 posterolateral reconstructions) were observed 2 to
      13.7 years postoperatively. All major posterolateral structures were surgically
      restored. The procedure represented a primary reconstruction in 7 patients and a
      revision in 6 patients. Anterior cruciate ligament ruptures were found in 7
      patients and bicruciate ruptures in 5 patients, all of which were reconstructed.
      The rehabilitation protocol allowed immediate knee motion from 0 degrees to 90
      degrees but included protection against lateral joint loads to prevent graft
      stretching and failure. The results were determined by a knee examination, stress
      radiography, KT-2000 arthrometer, the Cincinnati Knee Rating System, and the
      International Knee Documentation Committee Rating System. RESULTS: Significant
      improvements were found at follow-up for pain (P = .0001), swelling (P = .02),
      patient rating of the overall knee condition (P < .001), walking (P < .05), and
      stair climbing (P < .05). Thirteen of the 14 (93%) reconstructions restored
      normal or nearly normal lateral joint opening and external tibial rotation and 1
      failed. The anterior cruciate ligament reconstructions were normal or nearly
      normal in 11 knees and abnormal in 1 knee. CONCLUSIONS: The anatomical
      posterolateral procedure was effective in restoring normal limits to lateral
      joint opening and external tibial rotation, allowed immediate knee motion, and
      appeared to protect other soft tissue repairs.

PMID- 17021311
TI  - Clinical examination and ultrasound of self-reported snapping hip syndrome in
      elite ballet dancers.
AB  - BACKGROUND: Although snapping hip syndrome is commonly reported in ballet
      dancers, the prevalence, impact, and underlying mechanism of this condition have
      not been formally studied within a cohort of dancers. PURPOSE: To determine the
      prevalence, associated factors, and mechanisms of snapping hip and to investigate
      self-reported snapping with physical and ultrasound examination. STUDY DESIGN:
      Cross-sectional study; Level of evidence, 3. METHODS: A snapping hip
      questionnaire was completed by 87 unselected elite ballet dancers at 2
      institutions. Twenty-six of the dancers (50 hips) who were able to voluntarily
      snap their hips were selected from this group for further physical examination by
      2 clinicians to determine whether there was a palpable snap, and each underwent
      an ultrasound examination of his or her hips. RESULTS: Ninety-one percent of
      dancers reported snapping hip, of which most (80%) had bilateral symptoms. Fifty
      eight percent had pain associated with the snap, and 7% had taken time off dance
      because of this condition. Sixty percent of the dancers could voluntarily snap
      their hip. One or more of 3 dance movements elicited the snapping in 81%. The
      clinicians could palpate 46 of the 50 self-reported snapping hips. Ultrasound
      showed a snapping iliopsoas tendon in 59% of the hips and the iliotibial band
      snapping in 4%. In one third of cases, ultrasound was not helpful in identifying
      the cause of the snapping. CONCLUSION: Snapping hip is extremely common in ballet
      dancers. Some dancers have significant pain, yet many are asymptomatic. Self
      reported snapping is likely to be palpable by the clinician. Iliotibial band
      snapping is evident by physical examination and ultrasound. Iliopsoas snapping
      was most common and required ultrasonic confirmation.

PMID- 17021312
TI  - Competitive surfing injuries: a prospective study of surfing-related injuries
      among contest surfers.
AB  - BACKGROUND: Surfing is a sport that has been growing rapidly in popularity, yet
      little is known about surfing injuries. PURPOSE: To calculate an accurate injury
      rate for competitive surfing and to describe the relative frequency, mechanisms,
      and risk factors for acute surfing injuries. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: This prospective study of acute competitive surfing
      injuries was carried out at 32 professional and amateur surfing contests
      worldwide between 1999 and 2005. All acute injuries sustained during competition
      were recorded by on-site medical personnel. The wave size, type of seafloor, and
      number of surfing heats were also recorded for each day. The total number of
      injuries was divided by the total number of athlete exposures to determine injury
      rates. A multiple logistic regression was used to determine risk factors for
      injury. RESULTS: There were 116 injuries documented, 89 of which occurred during
      competition. There were 15,675 athlete exposures, yielding an injury rate of 5.7
      per 1000 athlete exposures, or 13 per 1000 hours of competitive surfing. There
      were 6.6 significant injuries per 1000 hours of competitive surfing. Risk of
      injury was 2.4 (95% confidence interval, 1.5-3.9) times greater when surfing in
      waves overhead or bigger relative to smaller waves and 2.6 (95% confidence
      interval, 1.3-5.2) times greater when surfing over a rock or reef bottom relative
      to a sandy bottom. CONCLUSION: There were 13 acute surfing injuries per 1000
      hours of competitive surfing. The risk of injury was more than doubled when
      surfing in large waves or over a hard seafloor.

PMID- 17021313
TI  - Promotion of service integration among home visiting programs and community
      coalitions working with low-income, pregnant, and parenting women.
AB  - This study assessed service integration promoted by home visitors and community
      coalitions in Baltimore's Comprehensive Family Support Strategy. The study first
      assessed home visitors' coordination of services for their clients. Two yearly
      home visitors surveys (n = 32) assessed changes in their perceptions of 11
      community resources' availability, service quality, and referrals made to those
      resources. There were statistically significant increases in the percentage of
      home visitors who (a) reported availability of seven resources, (b) gave high
      service quality ratings for six resources, and (c) referred clients to all 11
      resources. The study also assessed six community coalitions' actions to promote
      service integration during 1 year through observation of coalition meetings.
      Coalitions discussing more service integration exhibited greater increases in
      home visitors' perceptions of high service quality and referrals. Home visiting
      practitioners should consider including coalitions as part of their program
      models in order to better link clients to appropriate community resources.

PMID- 17021314
TI  - Images in clinical medicine. Arteriovenous fistula on CT angiography.

PMID- 17021316
TI  - Tracing atrial fibrillation--100 years.

PMID- 17021315
TI  - The price of sight--ranibizumab, bevacizumab, and the treatment of macular
      degeneration.

PMID- 17021317
TI  - An aging un-American.

PMID- 17021318
TI  - Ranibizumab for neovascular age-related macular degeneration.
AB  - BACKGROUND: Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that
      neutralizes all active forms of vascular endothelial growth factor A--has been
      evaluated for the treatment of neovascular age-related macular degeneration.
      METHODS: In this multicenter, 2-year, double-blind, sham-controlled study, we
      randomly assigned patients with age-related macular degeneration with either
      minimally classic or occult (with no classic lesions) choroidal
      neovascularization to receive 24 monthly intravitreal injections of ranibizumab
      (either 0.3 mg or 0.5 mg) or sham injections. The primary end point was the
      proportion of patients losing fewer than 15 letters from baseline visual acuity
      at 12 months. RESULTS: We enrolled 716 patients in the study. At 12 months, 94.5%
      of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost
      fewer than 15 letters, as compared with 62.2% of patients receiving sham
      injections (P<0.001 for both comparisons). Visual acuity improved by 15 or more
      letters in 24.8% of the 0.3-mg group and 33.8% of the 0.5-mg group, as compared
      with 5.0% of the sham-injection group (P<0.001 for both doses). Mean increases in
      visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg
      group, as compared with a decrease of 10.4 letters in the sham-injection group
      (P<0.001 for both comparisons). The benefit in visual acuity was maintained at 24
      months. During 24 months, presumed endophthalmitis was identified in five
      patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab.
      CONCLUSIONS: Intravitreal administration of ranibizumab for 2 years prevented
      vision loss and improved mean visual acuity, with low rates of serious adverse
      events, in patients with minimally classic or occult (with no classic lesions)
      choroidal neovascularization secondary to age-related macular degeneration.
      (ClinicalTrials.gov number, NCT00056836 [ClinicalTrials.gov].).

PMID- 17021319
TI  - Ranibizumab versus verteporfin for neovascular age-related macular degeneration.
AB  - BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal
      antibody Fab that neutralizes all active forms of vascular endothelial growth
      factor A--with photodynamic therapy with verteporfin in the treatment of
      predominantly classic neovascular age-related macular degeneration. METHODS:
      During the first year of this 2-year, multicenter, double-blind study, we
      randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal
      injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or
      monthly sham injections plus active verteporfin therapy. The primary end point
      was the proportion of patients losing fewer than 15 letters from baseline visual
      acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given
      0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters,
      as compared with 64.3% of those in the verteporfin group (P<0.001 for each
      comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg
      group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin
      group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters
      in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a
      decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison).
      Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis
      occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS:
      Ranibizumab was superior to verteporfin as intravitreal treatment of
      predominantly classic neovascular age-related macular degeneration, with low
      rates of serious ocular adverse events. Treatment improved visual acuity on
      average at 1 year. (ClinicalTrials.gov number, NCT00061594
      [ClinicalTrials.gov].).

PMID- 17021320
TI  - Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic
      rhinitis.
AB  - BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens
      offers a new approach to allergen immunotherapy that reduces acute allergic
      responses. METHODS: We conducted a randomized, double-blind, placebo-controlled
      phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen,
      conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory
      sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients
      received six weekly injections of the AIC or placebo vaccine before the first
      ragweed season and were monitored during the next two ragweed seasons. RESULTS:
      There was no pattern of vaccine-associated systemic reactions or clinically
      significant laboratory abnormalities. AIC did not alter the primary end point,
      the vascular permeability response (measured by the albumin level in nasal-lavage
      fluid) to nasal provocation. During the first ragweed season, the AIC group had
      better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak
      season daily nasal symptom diary scores (P=0.02), and midseason overall quality
      of-life scores (P=0.05) than the placebo group. AIC induced a transient increase
      in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1
      specific IgE antibody. A reduction in the number of interleukin-4-positive
      basophils in AIC-treated patients correlated with lower rhinitis visual-analogue
      scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the
      subsequent ragweed season, with improvements over placebo in peak-season rhinitis
      visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores
      (P=0.02). The seasonal specific IgE antibody response was again suppressed, with
      no significant change in IgE antibody titer during the ragweed season (P=0.19).
      CONCLUSIONS: In this pilot study, a 6-week regimen of the AIC vaccine appeared to
      offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis.
      (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).

PMID- 17021321
TI  - Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion.
AB  - BACKGROUND: Severe, often refractory anemia is characteristic of the
      myelodysplastic syndrome associated with chromosome 5q31 deletion. We
      investigated whether lenalidomide (CC5013) could reduce the transfusion
      requirement and suppress the abnormal 5q31- clone in patients with this disorder.
      METHODS: One hundred forty-eight patients received 10 mg of lenalidomide for 21
      days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes
      were assessed after 24 weeks of treatment by an intention-to-treat analysis.
      RESULTS: Among the 148 patients, 112 had a reduced need for transfusions (76%;
      95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74)
      no longer required transfusions, regardless of the karyotype complexity. The
      response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1
      to 49) and sustained; the median duration of transfusion independence had not
      been reached after a median of 104 weeks of follow-up. The maximum hemoglobin
      concentration reached a median of 13.4 g per deciliter (range, 9.2 to 18.6), with
      a corresponding median rise of 5.4 g per deciliter (range, 1.1 to 11.4), as
      compared with the baseline nadir value before transfusion. Among 85 patients who
      could be evaluated, 62 had cytogenetic improvement, and 38 of the 62 had a
      complete cytogenetic remission. There was complete resolution of cytologic
      abnormalities in 38 of 106 patients whose serial bone marrow samples could be
      evaluated. Moderate-to-severe neutropenia (in 55% of patients) and
      thrombocytopenia (in 44%) were the most common reasons for interrupting treatment
      or adjusting the dose of lenalidomide. CONCLUSIONS: Lenalidomide can reduce
      transfusion requirements and reverse cytologic and cytogenetic abnormalities in
      patients who have the myelodysplastic syndrome with the 5q31 deletion.
      (ClinicalTrials.gov number, NCT00065156 [ClinicalTrials.gov].).

PMID- 17021322
TI  - Clinical practice. Prevention of meningococcal disease.

PMID- 17021323
TI  - Age-related macular degeneration.

PMID- 17021324
TI  - Images in clinical medicine. Yellow palms and soles in diabetes mellitus.

PMID- 17021325
TI  - Clinical problem-solving. Lost in transcription.

PMID- 17021326
TI  - A very effective treatment for neovascular macular degeneration.

PMID- 17021327
TI  - Inhaled carbon and lung function in children.

PMID- 17021328
TI  - N-acetylcysteine and contrast-induced nephropathy.

PMID- 17021329
TI  - Iodine nutrition--more is better.

PMID- 17021330
TI  - More on case 7-2006.

PMID- 17021331
TI  - The new era of medical imaging.

PMID- 17021332
TI  - Culture of T. whipplei from the stool of a patient with Whipple's disease.

PMID- 17021333
TI  - Penile oxygen saturation in the flaccid and erect penis in men with and without
      erectile dysfunction.
AB  - It is believed that a chronic state of corporal oxygen desaturation or hypoxemia
      secondary to the loss of nocturnal erections is a fundamental pathophysiological
      cause of erectile dysfunction (ED). Limited invasive blood gas measurements in
      human models have shown decreased oxygen tension in vasculogenic impotence.
      Normative data on flaccid and erect oxygen saturation (StO(2)) levels are lacking
      due to the invasive nature of blood gas determinations. Our objective was to
      determine StO(2) in the flaccid and erect penis in men with and without ED using
      a tissue oximeter. This FDA-approved instrument provides instantaneous,
      noninvasive, painless local tissue StO(2) measurements, which highly correlate to
      blood gas data. The study population included 171 men (18-90 years) who presented
      to one andrologist. They completed the Sexual Health Inventory for Men (SHIM)
      based on pharmacologically unassisted erectile function and had penile StO(2)
      measurements taken. 64 of these men had repeat measurements after PGE-1 induced
      erections. There are significant differences (P<.001) in corporal and glanular
      StO(2) in the flaccid (right corpora, 45.23%; left corpora, 52.50%) and erect
      state (right corpora, 76.58; left corpora, 80.42). Men with ED (right corpora,
      45.04% vs 53.58%; P=.02; and left corpora, 50.95% vs 58.78%; P=.03) have
      significantly lower corporal penile StO(2). Future prospective data collection
      can correlate penile StO(2) in specific populations, such as diabetics and RRP
      patients. This may help further elucidate the relationship between corporal
      hypoxia and the development and progression of ED and possibly its treatment and
      prevention.

PMID- 17021334
TI  - First steps in the development of a functional assay for human sperm using pig
      oocytes.
AB  - The use of mammalian oocytes to assess human sperm functionality could be a
      helpful tool with potential applications in clinical and research programs. In an
      attempt to develop the pig model, the aim of the present work was to study the
      interaction between human spermatozoa and pig oocytes at the zona pellucida (ZP),
      the oolemma, and the ooplasm levels. In vitro matured pig oocytes and human
      spermatozoa from fertile and low-fertility donors were employed. The induction of
      the acrosome reaction by the ZP, the ability of the sperm to penetrate the oocyte
      after coincubation, and the male pronuclear formation after ICSI were evaluated.
      Human spermatozoa can bind to pig ZP and undergo the acrosome reaction (15% to
      58%, depending on the individual); they are not able to fuse with the oolemma but
      they can decondense and form a male pronucleus (40%-100%) when injected into pig
      oocytes. In conclusion, this study shows that pig oocytes can be a useful model
      to assess human sperm functionality.

PMID- 17021335
TI  - Change of sexual function in patients before and after Ho:YAG laser enucleation
      of the prostate.
AB  - The aim of this study is to evaluate the effect of Ho:YAG laser enucleation of
      the prostate (HOLEP) to the sexual function of patients with benign prostatic
      hyperplasia (BPH). In the course of the study, 108 patients with BPH were
      recruited and accepted treatment with HOLEP. The effectiveness of treatment was
      evaluated by flow rate and the International Prostate Symptom Score (IPSS) before
      HOLEP and 6 months afterwards. Meanwhile, the sexual functions were evaluated
      with the Danish Prostate Symptom Score Sexual Function Questionnaire (DanPSS
      Sex). Before and 6 months after HOLEP treatment, the mean residual urine volume
      was reduced from 106.0 +/- 51.7 mL to 5.6 +/- 1.7 mL (P<.01), maximum flow rate
      was improved from 7.2 +/- 3.9 mL/s to 21.7 +/- 1.3 mL/s (P<.01), nocturia
      frequency was reduced from 5.5 to 1.5 (P<.01), and the mean IPSS score was
      decreased from 19.4 +/- 5.6 to 7.4 +/- 2.6 (P<.01). The proportion of patients
      satisfied with their libido was 55% before HOLEP and 57% 6 months afterwards,
      while 23.5% of the patients had no libido before and after HOLEP; 37% of the
      patients were satisfied with their erection before HOLEP and 40% after 6 months;
      30% of the patients had completely satisfactory sex life before HOLEP, and 32%
      did 6 months later. The corresponding percentages of fully impotent patients
      increased from 33% before the procedure to 35% 6 months postoperation. Early
      morning erections were reported by 45% of the patients before the procedure and
      by 62% 6 months later (P<.01). In 70% of the patients with normal sex life,
      ejaculation was retrograde 6 months after HOLEP (P<.01). HOLEP does not affect
      the sexual function of patients with BPH but does did improve the ability of
      early morning erection, while causing retrograde ejaculation.

PMID- 17021336
TI  - The analysis of meiotic segregation patterns and aneuploidy in the spermatozoa of
      father and son with translocation t(4;5)(p15.1;p12) and the prediction of the
      individual probability rate for unbalanced progeny at birth.
AB  - Reciprocal chromosomal translocations (RCT) have long been recognized as
      important etiological factors in reproductive failure. In the present study, the
      meiotic segregation patterns of the spermatozoa of two related t(4;5)(p15.1;p12)
      carriers (proband and his father) were compared to the empirical data from a
      three-generation pedigree for risk assessment. Cytogenetic analysis of the
      metaphase chromosomes was performed, and triple color fluorescence in situ
      hybridization (FISH) was applied to the sperm heads. Similar patterns of meiotic
      segregation were observed for both carriers, despite the finding of
      teratozoospermia in the proband but not in his father. In addition, an increase
      of aneuploidy in chromosome 15 in the proband and aneuploidy of chromosomes X and
      Y in the father were observed. The high rate of miscarriages (6/10 pregnancies
      and 4/7 pregnancies after ascertainment correction) in this family could be
      explained by the genetically unbalanced karyotype and fertilization mediated by
      the unbalanced spermatozoa observed for both men at a frequency of more than 60%.
      The risk assessment for unfavorable pregnancy outcomes was predicted as 1.6% for
      unbalanced progeny at birth and about 30% for miscarriage. These figures may be
      used as guidelines for the genetic counseling of families with similar RCT.

PMID- 17021339
TI  - Interviews with andrologists (part 1). Interview by Katja Wolski.

PMID- 17021337
TI  - Effects of the chemotherapy cocktail used to treat testicular cancer on sperm
      chromatin integrity.
AB  - The incidence of testicular cancer has increased dramatically over the past 50
      years. Advances in treatment, which include the coadministration of bleomycin,
      etoposide, and cis-platinum (BEP), have brought the cure rate to over 90%. After
      treatment, most patients go through a temporary period of azoo/oligozoospermia.
      Although the sperm concentration in approximately 80% of the patients returns to
      at least 10 million/mL, little is known about the integrity of the chromatin of
      their germ cells. Using an animal model, we assessed DNA integrity in the
      spermatozoa of male rats treated for 3, 6 or 9 weeks with BEP at doses, adjusted
      for surface area, equivalent to 0X, 1/3X, 2/3X, or 1X of the human dose. We did
      not observe any difference in protamination content, as assessed by the
      chromomycin A3 (CMA3) assay. After 9 weeks of 1X treatment, the susceptibility of
      DNA to denaturation evaluated by the sperm chromatin structure assay
      (SCSA/acridine orange assay (AO) was increased, as well as the number of single
      and double DNA strand breaks measured by the TUNEL and COMET assays. Parameters
      obtained from the AO and TUNEL assays were highly correlated with the motility of
      the spermatozoa, suggesting that conventional sperm analysis parameters can serve
      as a good indicator of chromatin integrity and vice versa. Correlation studies
      also suggested that the parameters obtained with the different assays do not
      overlap, but complement each other. Thus, BEP treatment altered spermatozoal
      chromatin quality, and these alterations may impact adversely on progeny outcome.

PMID- 17021340
TI  - Spermatozoa have decreased antioxidant enzymatic capacity and increased reactive
      oxygen species production during aging in the Brown Norway rat.
AB  - As the proportion of aged males attempting to reproduce continues to rise, so
      does the concern regarding the quality of spermatozoa from aged men. An imbalance
      between the generation of reactive oxygen species (ROS) and cellular antioxidant
      defenses, as occurs in aging, ultimately leads to decreased protein, lipid, and
      DNA quality. Spermatozoa are highly susceptible to oxidative damage, and thus an
      age-related shift in redox status may have serious implications for fertility.
      Therefore, we examined the effect of age on antioxidant enzymatic activity, ROS
      production, and extent of lipid peroxidation in both caput and cauda epididymal
      spermatozoa from young (4-month-old) and old (21-month-old) Brown Norway rats.
      Glutathione peroxidase (Gpx1, Gpx4) and superoxide dismutase (SOD) enzymes had
      decreased activity in aging spermatozoa. Immunofluorescence studies indicated
      that Gpx4 expression was decreased in both the head and midpiece regions of
      spermatozoa in aged animals. The decrease in nuclear Gpx4 points to a novel
      potential mechanism that may explain the previously noted decreased levels of
      protamine disulfide bonds in aged sperm nuclei. Further, hydrogen peroxide (H2O2)
      and superoxide (O2(.-)) production were increased significantly in aging
      spermatozoa. Finally, lipid peroxidation was found to be drastically increased in
      aged spermatozoa. Taken together, these results suggest a decreased capacity for
      aged spermatozoa to handle oxidative stress and provide a potential basis for
      understanding the underlying cause of decreased quality of spermatozoa during
      aging.

PMID- 17021341
TI  - Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation
      of testicular function in immature male rats.
AB  - We investigated the effects of 3-methyl-4-nitrophenol (4-nitro-m-cresol, PNMC)
      isolated from diesel exhaust particles (DEP) on the reproductive functions of
      male rats. Twenty-eight-day-old rats were injected subcutaneously with PNMC (1,
      10, or 100 mg/kg) daily for 5 days. The weights of the epididymis, seminal
      vesicle, and Cowper gland were significantly decreased in rats treated with 10
      mg/kg PNMC. The plasma concentrations of luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) were significantly increased by PNMC at 100 mg/kg.
      However, the plasma concentrations of testosterone and immunoreactive (ir)
      inhibin were significantly decreased by PNMC at 100 mg/kg. The testosterone
      content of the testicles was significantly decreased in the group treated with
      100 mg/kg PNMC compared with the control group. Furthermore, testicular
      concentration of ir-inhibin was significantly decreased by PNMC at 1 mg/kg or 100
      mg/kg. To investigate the direct effects of PNMC on the secretion of LH and FSH
      from the anterior pituitary gland, and on the secretion of testosterone from the
      testes, we exposed cultured anterior pituitary and interstitial Leydig cells to
      PNMC (10(-6), 10(-5), 10(-4) M) with or without gonadotropin-releasing hormone
      (GnRH; 10 nM) (for the LH and FSH tests) and human chorionic gonadotropin (hCG;
      0.1 IU/mL) (for the testosterone test) for 24 hours. PNMC did not change either
      the basal or GnRH-stimulated levels of FSH and LH secretion. However, PNMC
      significantly inhibited both basal and hCG-stimulated testosterone production.
      These findings suggest that PNMC has a direct effect on the testes of immature
      male rats, causing a reduction in testosterone secretion.

PMID- 17021342
TI  - Transmission of mouse minute virus (MMV) but not mouse hepatitis virus (MHV)
      following embryo transfer with experimentally exposed in vivo-derived embryos.
AB  - The present study investigated the presence and location of fluorescent
      microspheres having the size of mouse hepatitis virus (MHV) and of mouse minute
      virus (MMV) in the zona pellucida (ZP) of in vivo-produced murine embryos, the
      transmission of these viruses by embryos during embryo transfer, and the time of
      seroconversion of recipients and pups. To this end, fertilized oocytes and
      morulae were exposed to different concentrations of MMVp for 16 h, while 2-cell
      embryos and blastocysts were coincubated for 1 h. In addition, morulae were
      exposed to MHV-A59 for 16 h. One group of embryos was washed, and the remaining
      embryos remained unwashed before embryo transfer. Serological analyses were
      performed by means of ELISA to detect antibodies to MHV or MMV in recipients and
      in progeny on Days 14, 21, 28, 42, and 63 and on Days 42, 63, 84, 112, 133, and
      154, respectively, after embryo transfer. Coincubation with a minimum of 10(5)/ml
      of fluorescent microspheres showed that particles with a diameter of 20 nm but
      not 100 nm crossed the ZP of murine blastocysts. Washing generally led to a 10
      fold to 100-fold reduction of MMVp. Washed MMV-exposed but not MHV-exposed
      embryos led to the production of antibodies independent of embryonic stage and
      time of virus exposure. Recipients receiving embryos exposed to a minimum of
      10(7) mean tissue culture infective dose (TCID(50))/ml of MHV-A59 and 10(2)
      TCID(50)/ml of MMVp seroconverted by Day 42 after embryo transfer. The results
      indicate that MMV but not MHV can be transmitted to recipients even after washing
      embryos 10 times before embryo transfer.

PMID- 17021343
TI  - Leukemia inhibitory factor enhances formation of germ cell colonies in neonatal
      mouse testis culture.
AB  - Spermatogonial stem cells continuously divide in the testis to support
      spermatogenesis throughout the life of adult male animals. Although very few
      spermatogonial stem cells are present in vivo, we recently succeeded in expanding
      these cells in vitro. Germ cells from postnatal testes were able to proliferate
      in the presence of several types of cytokines, and they formed uniquely shaped
      colonies of spermatogonia (germline stem or GS cells). These cells reinitiated
      normal spermatogenesis when transplanted into seminiferous tubules. However, much
      remains unknown about the contributions of cytokines to successful stem cell
      culture. In the present study, we examined the role of leukemia inhibitory factor
      (LIF) in GS cell culture. We found that the addition of LIF to newborn testis
      cell culture enhances the formation of germ cell colonies. Ciliary neurotrophic
      factor, but not oncostatin M, had the same effect, although they both bind to the
      IL-6ST (gp130) receptor. On the other hand, GS cells could be established from
      pup or adult testes in the absence of LIF. No phenotypic or functional difference
      was found between GS cells established from different stages, and normal
      offspring were born from pup-derived GS cells that had been maintained in the
      absence of LIF, indicating that LIF per se is not involved in the self-renewal of
      GS cells. These results demonstrate that LIF is useful in the initiation of GS
      cell culture and suggest that LIF or a related cytokine is involved in the
      maturation of gonocytes into spermatogonia.

PMID- 17021344
TI  - The proximal Gata4 promoter directs reporter gene expression to sertoli cells
      during mouse gonadal development.
AB  - The GATA4 transcription factor is an important developmental determinant for many
      organs, such as the heart, gut, and testis. Despite this pivotal role, our
      understanding of the transcriptional mechanisms that control the proper
      spatiotemporal expression of the GATA4 gene remains limited. We have generated
      transgenic mice expressing a green fluorescent protein (GFP) marker under the
      control of rat Gata4 5' flanking sequences. Several GATA4-expressing organs
      displayed GFP fluorescence, including the heart, intestine, and pancreas. In the
      gonads, while GATA4 is expressed in pregranulosa, granulosa, and theca ovarian
      cells, and Sertoli, Leydig, and peritubular testicular cells, the first 5 kb of
      Gata4 regulatory sequences immediately upstream of exon 1 were sufficient to
      direct GFP reporter expression only in testis and, specifically, in Sertoli
      cells. Onset of GFP expression occurred after Sertoli cell commitment and was
      maintained in these cells throughout development to adulthood. In vitro studies
      revealed that the first 118 bp of the Gata4 promoter is sufficient for full basal
      activity in several GATA4-expressing cell lines. Promoter mutagenesis and DNA
      binding experiments identified two GC-box motifs and, particularly, one E-box
      element within this -118-bp region that are crucial for its activity. Further
      analysis revealed that members of the USF family of transcription factors,
      especially USF2, bind to and activate the Gata4 promoter via this critical E-box
      motif.

PMID- 17021345
TI  - Decidual stromal cell response to paracrine signals from the trophoblast:
      amplification of immune and angiogenic modulators.
AB  - During the invasive phase of implantation, trophoblasts and maternal decidual
      stromal cells secrete products that regulate trophoblast differentiation and
      migration into the maternal endometrium. Paracrine interactions between the
      extravillous trophoblast and the maternal decidua are important for successful
      embryonic implantation, including establishing the placental vasculature,
      anchoring the placenta to the uterine wall, and promoting the immunoacceptance of
      the fetal allograph. To our knowledge, global crosstalk between the trophoblast
      and the decidua has not been elucidated to date, and the present study used a
      functional genomics approach to investigate these paracrine interactions. Human
      endometrial stromal cells were decidualized with progesterone and further treated
      with conditioned media from human trophoblasts (TCM) or, as a control, with
      control conditioned media (CCM) from nondecidualized stromal cells for 0, 3, and
      12 h. Total RNA was isolated and processed for analysis on whole-genome, high
      density oligonucleotide arrays containing 54,600 genes. We found that 1374 genes
      were significantly upregulated and that 3443 genes were significantly
      downregulated after 12 h of coincubation of stromal cells with TCM, compared to
      CCM. Among the most upregulated genes were the chemokines CXCL1 (GRO1) and
      IL8,CXCR4, and other genes involved in the immune response (CCL8 [SCYA8],
      pentraxin 3 (PTX3), IL6, and interferon-regulated and -related genes) as well as
      TNFAIP6 (tumor necrosis factor alpha-induced protein 6) and metalloproteinases
      (MMP1, MMP10, and MMP14). Among the downregulated genes were growth factors,
      e.g., IGF1, FGF1, TGFB1, and angiopoietin-1, and genes involved in Wnt signaling
      (WNT4 and FZD). Real-time RT-PCR and ELISAs, as well as immunohistochemical
      analysis of human placental bed specimens, confirmed these data for
      representative genes of both up- and downregulated groups. The data demonstrate a
      significant induction of proinflammatory cytokines and chemokines, as well as
      angiogenic/static factors in decidualized endometrial stromal cells in response
      to trophoblast-secreted products. The data suggest that the trophoblast acts to
      alter the local immune environment of the decidua to facilitate the process of
      implantation and ensure an enriched cytokine/chemokine environment while limiting
      the mitotic activity of the stromal cells during the invasive phase of
      implantation.

PMID- 17021346
TI  - Leptin promotes cell proliferation and survival of trophoblastic cells.
AB  - Leptin, the 16-kDa protein product of the obese gene, was originally considered
      as an adipocyte-derived signaling molecule for the central control of metabolism.
      However, leptin has been suggested to be involved in other functions during
      pregnancy, particularly in placenta. In the present work, we studied a possible
      effect of leptin on trophoblastic cell proliferation, survival, and apoptosis.
      Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines
      showed a stimulatory effect on cell proliferation up to 3 and 2.4 times,
      respectively, measured by (3)H-thymidine incorporation and cell counting. These
      effects were time and dose dependent. Maximal effect was achieved at 250 ng
      leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by
      inhibiting endogenous leptin expression with 2 microM of an antisense
      oligonucleotide (AS), cell proliferation was diminished. We analyzed cell
      population distribution during the different stages of cell cycle by fluorescence
      activated cell sorting, and we found that leptin treatment displaced the cells
      towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression,
      one of the key cell cycle-signaling proteins. Since proliferation and death
      processes are intimately related, the effect of leptin on cell apoptosis was
      investigated. Treatment with 2 microM leptin AS increased the number of apoptotic
      cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium
      iodide staining, and the caspase-3 activity was increased more than 2 fold. This
      effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we
      provide evidence that suggests that leptin is a trophic and mitogenic factor for
      trophoblastic cells by virtue of its inhibiting apoptosis and promoting
      proliferation.

PMID- 17021347
TI  - Epigenetic marks in cloned rhesus monkey embryos: comparison with counterparts
      produced in vitro.
AB  - Until now, no primate animals have been successfully cloned to birth with somatic
      cell nuclear transfer (SCNT) procedures, and little is known about the molecular
      events that occurred in the reconstructed embryos during preimplantation
      development. In many SCNT cases, epigenetic reprogramming of the donor nuclei
      after transfer into enucleated oocytes was hypothesized to be crucial to the
      reestablishment of embryonic totipotency. In the present study, we focused on two
      major epigenetic marks, DNA methylation and histone H3 lysine 9 (H3K9)
      acetylation, which we examined by indirect immunofluorescence and confocal laser
      scanning microscopy. During preimplantation development, 67% of two-cell- and 50%
      of eight-cell-cloned embryos showed higher DNA methylation levels than their in
      vitro fertilization (IVF) counterparts, which undergo gradual demethylation until
      the early morula stage. Moreover, whereas an asymmetric distribution of DNA
      methylation was established in an IVF blastocysts with a lower methylation level
      in the inner cell mass (ICM) than in the trophectoderm, in most cloned
      blastocysts, ICM cells maintained a high degree of methylation. Finally, two
      donor cell lines (S11 and S1-04) that showed a higher level of H3K9 acetylation
      supported more blastocyst formation after nuclear transfer than the other cell
      line (S1-03), with a relatively low level of acetylation staining. In conclusion,
      we propose that abnormal DNA methylation patterns contribute to the poor quality
      of cloned preimplantation embryos and may be one of the obstacles to successful
      cloning in primates.

PMID- 17021348
TI  - Production of recombinant orange-spotted grouper (Epinephelus coioides)
      luteinizing hormone in insect cells by the baculovirus expression system and its
      biological effect.
AB  - The cDNA sequence encoding orange-spotted grouper lhb (LHbeta) and cga (GTHalpha)
      subunits were cocloned into baculovirus transfer vectors and expressed in insect
      Sf9 cells. The results showed that two bands of 15.6 kDa and 11.4 kDa could be
      detected by SDS-PAGE and a band of 30 kDa could be detected by native PAGE. The
      recombinant grouper Lh (rgLh) could stimulate the secretion of testosterone (T)
      and estradiol-17beta (E2) from the gonad in a static incubation system in a time
      dependent, but not a dose-dependent, manner. Using in vivo bioassay, the mRNA
      levels of two aromatases (cyp19a1a [P450aromA] and cyp19a1b [P450aromB]), gnrh
      (GnRH), lhb, and cga in the pituitary, gonad, and hypothalamus were determined in
      different groups of orange-spotted groupers treated respectively with rgLh, human
      chorionic gonadotropin (hCG), and a culture medium of insect cells transformed
      with an expression vector without lhb and cga subunits. The mRNA levels of
      cyp19a1a and cyp19a1b rose dramatically after injecting rgLh intraperitoneally,
      which was consistent with the secretion of sex steroid hormones. Interestingly,
      the mRNA levels of gnrh dropped in the pituitary, hypothalamus, and gonad, and
      the mRNA levels of lhb and cga in the pituitary of the experimental group
      expressed at a higher level than that of the hCG group. These results are in
      accord with the long positive feedback loop of Lh on gonad sex steroid hormones
      and the short negative feedback loop of Lh on gnrh mRNA levels. These results
      indicate that the rgLh is successfully expressed by the baculovirus-insect
      expression system and that the rgLh has biological activity.

PMID- 17021349
TI  - Not the time to abandon the food frequency questionnaire: counterpoint.

PMID- 17021351
TI  - Not the time to abandon the food frequency questionnaire: point.

PMID- 17021350
TI  - Cotinine concentration in smokers from different countries: relationship with
      amount smoked and cigarette type.
AB  - This four-country study examined salivary cotinine as a marker for nicotine
      intake and addiction among smokers in relation to numbers and types of cigarettes
      smoked. Smoking characteristics of cigarette smokers in Brazil, China, Mexico,
      and Poland were identified using a standard questionnaire. Cotinine concentration
      was measured using a saliva sample from each participant; its relationship with
      numbers and types of cigarettes smoked was quantified by applying regression
      techniques. The main outcome measure was salivary cotinine level measured by gas
      chromatography. In all four countries, cotinine concentration increased linearly
      with cigarettes smoked up to 20 per day [11.3 ng/mL (95% confidence interval,
      10.5-12.2)] and then stabilized as the number of cigarettes exceeded 20 [6.8
      ng/mL per cigarette (95% confidence interval, 6.3-7.4) for up to 40 cigarettes].
      On average, smokers of regular cigarettes consumed more cigarettes and had higher
      cotinine levels than light cigarette smokers. Cotinine concentration per
      cigarette smoked did not differ between regular and light cigarette smokers.
      Results suggest a saturation point for daily nicotine intake and minimal or no
      reduction in nicotine intake by smoking light cigarettes.

PMID- 17021352
TI  - Reproducibility and expression of skin biomarkers in sun-damaged skin and actinic
      keratoses.
AB  - OBJECTIVES: To explore p53 and proliferating cell nuclear antigen (PCNA)
      expression and polyamine content as biomarkers in skin cancer chemoprevention
      trials, we evaluated their expression in early stages of UV-induced squamous cell
      tumorigenesis. METHODS: Biopsies were collected from three groups: 78 subjects
      with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32
      with previous squamous cell carcinoma. Participants with sun damage were
      randomized to sunscreen or no sunscreen. RESULTS: We found significant
      differences in p53 and polyamines in forearms from the sun-damaged group (11.5 +/
      1.2% for p53, 65.5 +/- 1.9 nmol/g for putrescine, and 187.7 +/- 3.3 nmol/g for
      spermidine) compared with the group with sun damage plus AK (20.9 +/- 2.3% for
      p53, P = 0.0001; 81.7 +/- 3.9 nmol/g for putrescine, P = 0.0001; 209.4 +/- 8.2
      nmol/g for spermidine, P < 0.06). PCNA was not different. When lesion histology
      was considered, there was a stepwise significant increase in p53 in biopsies
      without characteristics of AK compared with early AK (P = 0.02) and AK (P =
      0.0006) and a similar pattern for PCNA with the only significant difference
      between early AK and AK. There was a stepwise increase in putrescine and
      spermidine in normal, sun-damaged forearm, forearm from subjects with AK, and the
      AK lesion itself (P < 0.0001). No significant differences in p53 or polyamines
      were seen in 3-month biopsies or, as a result of sunscreen use, although PCNA in
      the sun-damaged group not using sunscreen decreased significantly. CONCLUSIONS:
      p53 expression and polyamines in skin were elevated in early stages of skin
      tumorigenesis and were not affected by sunscreen, adding validity to their use as
      biomarkers in skin cancer chemoprevention trials.

PMID- 17021354
TI  - Looking at the acinus with function tests: can you believe it?

PMID- 17021353
TI  - BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer
      before age 50.
AB  - BACKGROUND: Understanding the effect of oral contraceptives on risk of breast
      cancer in BRCA1 or BRCA2 mutation carriers is important because oral
      contraceptive use is a common, modifiable practice. METHODS: We studied 497 BRCA1
      and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been
      diagnosed with breast cancer. Case-control analyses were conducted using
      unconditional logistic regression with adjustments for family history and
      familial relationships and were restricted to subjects with a reference age under
      50 years. RESULTS: For BRCA1 mutation carriers, there was no significant
      association between risk of breast cancer and use of oral contraceptives for at
      least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12]
      or duration of oral contraceptive use (P(trend) = 0.62). For BRCA2 mutation
      carriers, there was no association with use of oral contraceptives for at least 1
      year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated
      risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08
      3.94) and with duration of use (OR(trend) per year of use, 1.08; P = 0.008).
      Similar results were obtained when we considered only use of oral contraceptives
      that first started in 1975 or later. CONCLUSIONS: We found no evidence overall
      that use of oral contraceptives for at least 1 year is associated with breast
      cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2
      mutation carriers, use of oral contraceptives may be associated with an increased
      risk of breast cancer among women who use them for at least 5 years. Further
      studies reporting results separately for BRCA1 and BRCA2 mutation carriers are
      needed to resolve this important issue.

PMID- 17021355
TI  - Biomarkers in acute exacerbation of chronic obstructive pulmonary disease: among
      the blind, the one-eyed is king.

PMID- 17021356
TI  - Just a spoonful of technology makes the protocol go down.

PMID- 17021357
TI  - Biomass fuels and health: the gap between global relevance and research activity.

PMID- 17021358
TI  - An official ATS statement: hepatotoxicity of antituberculosis therapy.
AB  - Drug-induced liver injury (DILI) is a problem of increasing significance, but has
      been a long-standing concern in the treatment of tuberculosis (TB) infection. The
      liver has a central role in drug metabolism and detoxification, and is
      consequently vulnerable to injury. The pathogenesis and types of DILI are
      presented, ranging from hepatic adaptation to hepatocellular injury. Knowledge of
      the metabolism of anti-TB medications and of the mechanisms of TB DILI is
      incomplete. Understanding of TB DILI has been hampered by differences in study
      populations, definitions of hepatotoxicity, and monitoring and reporting
      practices. Available data regarding the incidence and severity of TB DILI
      overall, in selected demographic groups, and in those coinfected with HIV or
      hepatitis B or C virus are presented. Systematic steps for prevention and
      management of TB DILI are recommended. These include patient and regimen
      selection to optimize benefits over risks, effective staff and patient education,
      ready access to care for patients, good communication among providers, and
      judicious use of clinical and biochemical monitoring. During treatment of latent
      TB infection (LTBI) alanine aminotransferase (ALT) monitoring is recommended for
      those who chronically consume alcohol, take concomitant hepatotoxic drugs, have
      viral hepatitis or other preexisting liver disease or abnormal baseline ALT, have
      experienced prior isoniazid hepatitis, are pregnant or are within 3 months
      postpartum. During treatment of TB disease, in addition to these individuals,
      patients with HIV infection should have ALT monitoring. Some experts recommend
      biochemical monitoring for those older than 35 years. Treatment should be
      interrupted and, generally, a modified or alternative regimen used for those with
      ALT elevation more than three times the upper limit of normal (ULN) in the
      presence of hepatitis symptoms and/or jaundice, or five times the ULN in the
      absence of symptoms. Priorities for future studies to develop safer treatments
      for LTBI and for TB disease are presented.

PMID- 17021359
TI  - Tuberculosis diagnostic tests: sensitivity, specificity, and comparing apples
      with apples.

PMID- 17021361
TI  - Computed tomography: a new gold standard for the clinical assessment of
      emphysema.

PMID- 17021362
TI  - Rapid measurement of deuterium-labeled long-chain fatty acids in plasma by HPLC
      ESI-MS.
AB  - Imbalanced fatty acid metabolism contributes significantly to the increased
      incidence of metabolic disorders. Isotope-labeled fatty acids (2H, 13C) provide
      efficient means to trace fatty acid metabolism in vivo. This study reports a new
      and rapid method for the quantification of deuterium-labeled fatty acids in
      plasma by HPLC-MS. The sample preparation protocol developed required only
      hydrolysis, neutralization, and quenching steps followed by high-performance
      liquid chromatography-electrospray ionization-mass spectrometry analysis in
      negative ion mode using single ion monitoring. Deuterium-labeled stearic acid (d7
      C18:0) was synthesized to reduce matrix interference observed with d5 analog,
      which improved the limit of detection (LOD) significantly, depending on the
      products analyzed. Linearity > 0.999 between the LOD (100 nM) and 30 microM,
      accuracy > 90%, precision > 88%, and adequate recovery in the dynamic range were
      obtained for d7-C18:0 and d7-oleic acid (C18:1). Upon oral dosing of d7-C18:0 in
      rats, the parent compound and its desaturation and beta-oxidation products, d7
      C18:1 and d7-C16:0, were circulating with a maximal concentration ranging from
      0.6 to 2.2 microM, with significant levels of d7-fatty acids detected for up to
      72 h.

PMID- 17021363
TI  - The neurobiology of obesity. Proceedings of the 7th International Symposium,
      Quebec City, Canada, November 4-5, 2005.

PMID- 17021364
TI  - What makes people fat? View from the chair.

PMID- 17021365
TI  - Central regulation of energy homeostasis intelligent design: how to build the
      perfect survivor.
AB  - The perfect survivor must be able to eat and store as many calories as possible
      when food is readily available as a buffer against periods of scarcity. He must
      also reduce energy expenditure when food is scarce and efficiently and accurately
      restore lost adipose stores when food is again available. These processes are
      dependent on information relayed to a distributed central network of metabolic
      sensing neurons through hard-wired neural, metabolic, and hormonal signals from
      the periphery. These sensing neurons engage neuroendocrine, autonomic, and motor
      processes involved in arousal, motor activity, and the ingestion, absorption,
      assimilation, storage, and expenditure of calories. A raised threshold in these
      metabolic sensors for detecting inhibitory signals from increasing adipose stores
      allows continued intake of excess calories when they are readily available.
      Unfortunately, this mechanism for surviving periods of feast and famine
      predisposes the perfect survivor to become obese when highly palatable, energy
      dense foods are readily available at low energetic cost. It further assures that
      raised adipose stores are metabolically defended against attempts to lower them.
      Thus, effective treatment of obesity will only come with a better understanding
      of the physiological, metabolic, and neurochemical processes that ensure this
      defense of an elevated body weight.

PMID- 17021366
TI  - Homeostatic and non-homeostatic pathways involved in the control of food intake
      and energy balance.
AB  - A neural network sensitive to leptin and other energy status signals stretching
      from the hypothalamus to the caudal medulla has been identified as the
      homeostatic control system for the regulation of food intake and energy balance.
      While this system is remarkably powerful in defending the lower limits of
      adiposity, it is weak in curbing appetite in a world of plenty. Another extensive
      neural system that processes appetitive and rewarding aspects of food intake is
      mainly interacting with the external world. This non-homeostatic system is
      constantly attacked by sophisticated signals from the environment, ultimately
      resulting in increased energy intake in many genetically predisposed individuals.
      Recent findings suggest a role for accumbens-hypothalamic pathways in the
      interaction between non-homeostatic and homeostatic factors that control food
      intake. Identification of the neural pathways that mediate this dominance of
      cortico-limbic processes over the homeostatic regulatory circuits in the
      hypothalamus and brainstem will be important for the development of behavioral
      strategies and pharmacological therapies in the fight against obesity.

PMID- 17021367
TI  - Fatty acid metabolism, the central nervous system, and feeding.
AB  - A potential role for fatty acid metabolism in the regulation of energy balance in
      the brain or in the periphery has been considered only recently. Fatty acid
      synthase (FAS) catalyzes the synthesis of long-chain fatty acids, whereas the
      breakdown of fatty acids by beta-oxidation is regulated by carnitine
      palmitoyltransferase-1, the rate-limiting enzyme for the entry of fatty acids
      into the mitochondria for oxidation. While the question of the physiological role
      of fatty acid metabolism remains to be resolved, studies indicate that inhibition
      of FAS or stimulation of carnitine palmitoyltransferase-1 using cerulenin or
      synthetic FAS inhibitors reduces food intake and incurs profound and reversible
      weight loss. Several hypotheses regarding the mechanisms by which these small
      molecules mediate their effects have been entertained. Centrally, these compounds
      alter the expression of hypothalamic neuropeptides, generally reducing the
      expression of orexigenic peptides. Whether through central, peripheral, or
      combined central and peripheral mechanisms, these compounds also increase energy
      consumption to augment weight loss. In vitro and in vivo studies indicate that at
      least part of C75's effects is mediated by modulation of adenosine monophosphate
      activated protein kinase, a member of an energy-sensing kinase family. These
      compounds, with chronic treatment, also alter gene expression peripherally to
      favor a state of enhanced energy consumption. Together, these effects raise the
      possibility that pharmacological alterations in fatty acid synthesis/degradation
      may serve as a target for obesity therapeutics.

PMID- 17021368
TI  - Leptin receptor signaling and action in the central nervous system.
AB  - The increasing incidence of obesity in developed nations represents an ever
      growing challenge to health care by promoting diabetes and other diseases. The
      discovery of the hormone, leptin, a decade ago has facilitated the acquisition of
      new knowledge regarding the regulation of energy balance. A great deal remains to
      be discovered regarding the molecular and anatomic actions of leptin, however.
      Here, we discuss the mechanisms by which leptin activates intracellular signals,
      the roles that these signals play in leptin action in vivo, and sites of leptin
      action in vivo. Using "reporter" mice, in which LRb-expressing (long form of the
      leptin receptor) neurons express the histological marker, beta-galactosidase,
      coupled with the detection of LRb-mediated signal transducer and activator of
      transcription 3 signaling events, we identified LRb expression in neuronal
      populations both within and outside the hypothalamus. Understanding the
      regulation and physiological function of these myriad sites of central leptin
      action will be a crucial next step in the quest to understand mechanisms of
      leptin action and energy balance.

PMID- 17021369
TI  - Circuitries involved in the regulation of energy homeostasis: view from the
      chair.

PMID- 17021370
TI  - Distributed neural control of energy balance: contributions from hindbrain and
      hypothalamus.
AB  - Data are reviewed that support the hypothesis that the neural control of energy
      expenditure is distributed among several brain sites. This view contrasts with
      that expressed most commonly in literature, that a single site-the arcuate
      hypothalamic nucleus-receives and integrates signals of relevance to energy
      status assessment and engages the effector circuits that orchestrate responses
      that maintain energy balance. The data reviewed support a contribution from
      medullary neurons, including those of the nucleus of the solitary tract, in the
      integration of signals of relevance to energy balance and in the issuing of
      commands to local behavioral and autonomic effectors. Experimental evidence is
      discussed that supports the following specific conclusions: hindbrain neurons
      integrate oral and gastrointestinal signals and issue commands to local motor
      circuits that control meal size; leptin's effect on food intake may be mediated,
      in part, by a direct action on the hindbrain neurons that respond to gastric
      distention; deprivation signals, such as the fall in leptin level, affect gene
      expression outside of the hypothalamus with reductions in proglucagon and
      proopiomelanocortin message seen in nucleus of the solitary tract-rich tissue;
      and that hindbrain neurons contribute to the control of energy expenditure seen
      with food deprivation and increases in expenditure after cold exposure or
      starvation. Future work is needed to define how the nucleus of the solitary tract
      and arcuate nodes of the central energy balance control network interact to
      collectively, or separately, influence specific aspects of energy balance control
      in the intact brain.

PMID- 17021371
TI  - Genetic dissection of neuronal pathways controlling energy homeostasis.
AB  - Recent research has identified a number of genes playing critical roles in the
      central regulation of energy homeostasis. Subsequently, models of the
      neurocircuitry regulating energy balance have been suggested, although their
      physiological relevance remains mostly untested. Using the Cre/loxP system, we
      can now genetically dissect these neurocircuits and establish the specific roles
      of these genes in small neuronal subpopulations. Here we focus on two receptors
      shown to be critical in the central regulation of energy homeostasis: leptin
      (LepR) and melanocortin-4 receptors (MC4R). Mice and humans deficient in either
      leptin or melanocortin signaling are severely obese. A prominent model of leptin
      action places the arcuate nucleus of the hypothalamus, and in particular arcuate
      proopiomelanocortin (POMC) neurons, at the center stage of energy balance
      regulation. By deleting LepR specifically from POMC neurons in mice, we showed
      that LepR on POMC neurons are required but not solely responsible for leptin's
      regulation of body weight homeostasis. Thus, LepR on other neurons must also be
      critically important in leptin-mediated regulation of body weight homeostasis.
      Data from MC4R-deficient mice have shown that MC4Rs regulate both sides of the
      energy intake/energy expenditure balance. Our recent experiments used MC4R
      deficient mice with restored MC4R expression only in the paraventricular
      hypothalamus and a subpopulation of amygdala neurons. We showed that MC4Rs in the
      paraventricular hypothalamus and/or amygdala are sufficient to control food
      intake but that MC4Rs elsewhere control energy expenditure, thereby discovering
      the novel concept of functional and anatomical divergence of MC4Rs.

PMID- 17021372
TI  - Synaptic plasticity in energy balance regulation.
AB  - Leptin regulates energy balance, in part, by modulating the activity of
      neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic
      arcuate nucleus. Leptin-deficient (ob/ob) mice differ from wild-type mice in the
      number of excitatory and inhibitory post-synaptic densities and currents onto NPY
      and POMC neurons. When leptin was delivered to ob/ob mice, the synaptic density
      rapidly normalized, an effect detectable within 6 hours, several hours before
      leptin's effect on food intake. Synaptic currents were also shifted toward wild
      type values in leptin-replaced ob/ob mice. These data suggest that leptin
      mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's
      behavioral effects. In an effort to determine whether the observed synaptic
      plasticity is leptin specific, we analyzed the effects of an orexigenic hormone,
      ghrelin, and anorexigenic hormone, estradiol. Ghrelin rearranged synapses in wild
      type animals to support suppressed POMC tone, whereas the estradiol triggered a
      robust increase in the number of excitatory, glutamate inputs of POMC neurons.
      The rearrangement of synapses by estradiol was leptin independent, because it was
      also evident in leptin- (ob/ob) and leptin receptor-deficient (db/db) mice and
      was paralleled with decreased food intake and increased energy expenditure in
      these mutant, obese animals. Such plasticity was also observed in other
      hypothalamic regions and extrahypothalamic sites. These observations raise the
      notion that synaptic plasticity is a major way through which peripheral metabolic
      hormones influence brain functions.

PMID- 17021373
TI  - Blood-brain barrier and energy balance.
AB  - The blood-brain barrier (BBB) plays a critical role in the transduction of
      signals between the central nervous system and peripheral tissues. It does so
      through several mechanisms, including the direct transport of peptides and
      regulatory proteins such as insulin and leptin. Another mechanism that may be
      important is the secretion by brain endothelial cells of substances that affect
      feeding, such as proinflammatory cytokines and NO. We have recently shown that
      the BBB is capable of receiving an input from one side and secreting a substance
      into the other. Additionally, BBB secretions can be modulated by substances that
      affect feeding, such as adiponectin and lipopolysaccharide.

PMID- 17021374
TI  - From fat to full: peripheral and central mechanisms controlling food intake and
      energy balance: view from the chair.

PMID- 17021375
TI  - Adipose tissue as an endocrine organ.
AB  - Adipose tissue plays a critical role in energy homeostasis, not only in storing
      triglycerides, but also responding to nutrient, neural, and hormonal signals and
      secreting adipokines that control feeding, thermogenesis, immunity, and
      neuroendocrine function. A rise in leptin signals satiety to the brain through
      receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine
      kinase, Janus kinase 2, and signal transducer and activator of transcription 3,
      leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte
      stimulating hormone and cocaine- and amphetamine-regulated transcript, and
      inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related
      peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin
      resistance, partly caused by induction of suppressor of cytokine signaling-3.
      Leptin falls rapidly during fasting and potently stimulates appetite, reduces
      thermogenesis, and mediates the inhibition of thyroid and reproductive hormones
      and activation of the hypothalamic-pituitary-adrenal axis. These actions are
      integrated by the paraventicular hypothalamic nucleus. Leptin also decreases
      glucose and stimulates lipolysis through central and peripheral pathways
      involving AMP-activated protein kinase (AMPK). Adiponectin is secreted
      exclusively by adipocytes and has been linked to glucose, lipid, and
      cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been
      associated with reduced adiponectin levels, whereas adiponectin treatment
      reverses these abnormalities partly through activation of AMPK in liver and
      muscle. Administration of adiponectin in the brain recapitulates the peripheral
      actions to increase fatty acid oxidation and insulin sensitivity and reduce
      glucose. Although putative adiponectin receptors are widespread in peripheral
      organs and brain, it is uncertain whether adiponectin acts exclusively through
      these targets. As with leptin, adiponectin requires the central melanocortin
      pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces
      glucose and lipids, at least in part, by activating AMPK in muscle and liver.

PMID- 17021376
TI  - Gut peptide signaling in the controls of food intake.
AB  - During a meal and after a meal, ingested nutrients alter the release of a variety
      of gut peptides that have the potential to modulate food intake. Such feedback
      peptide signaling can be conceptualized as having three outcomes: meal
      termination, inhibitory modulation of intake in subsequent meals, and orexigenic
      modulation. Cholecystokinin, pancreatic glucagons, and amylin are examples of
      peptides involved in meal termination. They are released rapidly with the onset
      of feeding and have short durations of action. Peptide YY(3-36) and glucagon-like
      peptide 1 are peptides for which longer-term feeding inhibitory actions have been
      proposed. They are released from the distal intestine and have longer durations
      of actions. Ghrelin is a gastric peptide that stimulates food intake after its
      exogenous administration. Plasma ghrelin levels fall with feeding and rise with
      food deprivation. All of these gut peptides have vagal or dorsal hindbrain
      mediation. Their potential as targets for the development of anti-obesity
      treatments is under study.

PMID- 17021377
TI  - Leptin resistance and obesity.
AB  - The prevalence of obesity, and the human and economic costs of the disease,
      creates a need for better therapeutics and better understanding of the
      physiological processes that balance energy intake and energy expenditure. Leptin
      is the primary signal from energy stores and exerts negative feedback effects on
      energy intake. In common obesity, leptin loses the ability to inhibit energy
      intake and increase energy expenditure; this is termed leptin resistance. This
      review discusses the evidence in support of leptin resistance in mouse models and
      humans and the possible mechanisms of leptin resistance.

PMID- 17021378
TI  - Rapid glucocorticoid actions in the hypothalamus as a mechanism of homeostatic
      integration.
AB  - The hypothalamic paraventricular nucleus (PVN) is a major integrative site for
      the control of homeostasis, including energy balance, through coordinated
      regulation of neuroendocrine and autonomic outputs. However, cross-talk
      regulation of PVN neuroendocrine and preautonomic systems is poorly understood.
      The stress response invokes the coordinated control of motor, hormonal, and
      vegetative systems to establish homeostasis after an environmental perturbation.
      Elevated stress levels of circulating glucocorticoids give rise to multiple,
      complex physiological effects. The complexity of the glucocorticoid actions is
      caused by the wide range of glucocorticoid target tissues and to the broad time
      scale over which the actions occur. Recent studies have revealed rapid
      glucocorticoid actions in the hypothalamus that may provide an integrative signal
      linking stress with the regulation of energy and fluid homeostasis.
      Glucocorticoids inhibit PVN and supraoptic nucleus neurons by stimulating a rapid
      synthesis and retrograde release of endocannabinoids, which suppress synaptic
      excitation through presynaptic CB1 receptor activation. The glucocorticoid
      induced endocannabinoid synthesis is mediated apparently by a novel membrane
      associated glucocorticoid receptor found in multiple subpopulations of
      hypothalamic neuroendocrine cells. It may, therefore, represent a mechanism for
      rapid glucocorticoid control of activity among different neuroendocrine systems
      to coordinate a global response to stress. In support of this, leptin, a
      circulating adipose signal that regulates food intake and energy expenditure
      through central actions, blocks the glucocorticoid-mediated endocannabinoid
      release in the PVN. This represents a means by which the regulation of stress and
      feeding may interface in the PVN, thus providing a possible mechanism for the
      integration of multiple homeostatic functions.

PMID- 17021379
TI  - Consensus features in amyloid fibrils: sheet-sheet recognition via a (polar or
      nonpolar) zipper structure.
AB  - Amyloid fibrils characterized as highly intractable thread-like species are
      associated with many neurodegenerative diseases. Although neither the mechanism
      of amyloid formation nor the origin of amyloid toxicity is currently completely
      understood, the detailed three-dimensional atomic structures of the yeast protein
      Sup35 and Abeta amyloid protein determined by recent experiments provide the
      first and important step towards the comprehension of the pathogenesis and
      aggregation mechanisms of amyloid diseases. By analyzing these two amyloid
      peptides which have available crystal structures and other amyloid sequences with
      proposed structures using computational simulations, we delineate three common
      features in amyloid organizations and amyloid structures. These could contribute
      to an improved understanding of the molecular mechanism of amyloid formation, the
      nature of the aggregation driving forces that stabilize these structures and the
      development of potential therapeutic agents against amyloid diseases.

PMID- 17021380
TI  - Molecular dynamics simulations of folding processes of a beta-hairpin in an
      implicit solvent.
AB  - Computer simulations of beta-hairpin folding are relatively difficult, especially
      those based on the explicit water model. This greatly limits the complete
      analysis and understanding of their folding mechanisms. In this paper, we use the
      generalized Born/solvent accessible implicit solvent model to simulate the
      folding processes of a nine-residue beta-hairpin. We find that the beta-hairpin
      can fold into its native structure very easily, even using the traditional
      molecular dynamics method. This allows us to extract 21 complete folding events
      and investigate the folding process sufficiently. Our results show that there
      exist four most stable states on the free energy landscape of the short peptide,
      one native state and three intermediates. We find that two of the non-native
      stable states have almost the same potential energy as the native state but with
      lower entropy. This suggests that the native state can be stabilized
      entropically. Furthermore, we find that the folding processes of this peptide
      have common features: to fold into its native state, the peptide undergoes a
      continuous collapsing-extending-recollapsing process to adjust the positions of
      the side chains in order to form the native middle inter-strand hydrogen bonds.
      The formations of these bonds are the key step of the folding process. Once these
      bonds are formed, the peptide can fold into the native state quickly.

PMID- 17021381
TI  - Dynamics of protein distributions in cell populations.
AB  - A population of cells exhibits wide phenotypic variation even if it is
      genetically homogeneous. In particular, individual cells differ from one another
      in the amount of protein they express under a given regulatory system under fixed
      conditions. Here we study how protein distributions in a population of the yeast
      S. cerevisiae are shaped by a balance of processes: protein production--an
      intracellular process--and protein dilution due to cell division--a population
      process. We measure protein distributions by employing reporter green
      fluorescence protein (gfp) under the regulation of the yeast GAL system under
      conditions where it is metabolically essential. Cell populations are grown in
      chemostats, thus allowing control of the environment and stable measurements of
      distribution dynamics over many generations. Despite the essential functional
      role of the GAL system in a pure galactose medium, steady-state distributions are
      found to be universally broad, with exponential tails and a large standard
      deviation-to-mean ratio. Under several different perturbations the dynamics of
      the distribution is observed to be asymmetric, with a much longer time to build a
      wide expression distribution from below compared with a fast relaxation of the
      distribution toward steady state from above. These results show that the main
      features of the protein distributions are largely determined by population
      effects and are less sensitive to the intracellular biochemical noise.

PMID- 17021382
TI  - Optimal gene partition into operons correlates with gene functional order.
AB  - Gene arrangement into operons varies between bacterial species. Genes in a given
      system can be on one operon in some organisms and on several operons in other
      organisms. Existing theories explain why genes that work together should be on
      the same operon, since this allows for advantageous lateral gene transfer and
      accurate stoichiometry. But what causes the frequent separation into multiple
      operons of co-regulated genes that act together in a pathway? Here we suggest
      that separation is due to benefits made possible by differential regulation of
      each operon. We present a simple mathematical model for the optimal distribution
      of genes into operons based on a balance of the cost of operons and the benefit
      of regulation that provides 'just-when-needed' temporal order. The analysis
      predicts that genes are arranged such that genes on the same operon do not skip
      functional steps in the pathway. This prediction is supported by genomic data
      from 137 bacterial genomes. Our work suggests that gene arrangement is not only
      the result of random historical drift, genome re-arrangement and gene transfer,
      but has elements that are solutions of an evolutionary optimization problem. Thus
      gene functional order may be inferred by analyzing the operon structure across
      different genomes.

PMID- 17021383
TI  - Morphology matters in immune cell chemotaxis: membrane asymmetry affects
      amplification.
AB  - A key mediator of eukaryotic chemotaxis is the asymmetric accumulation of
      phosphatidylinositol-3,4,5-triphosphate (PIP3) on the cell membrane. Recent work
      has focused on understanding how a shallow external gradient of chemoattractant
      leads to an amplified internal gradient of PIP3. In this paper we dissect what
      fraction of this amplification is derived biochemically by the signal
      transduction network and how much arises entirely from the effects of cell
      morphology. Here we identify and formalize the role of morphology in signal
      detection and demonstrate its effects through simulation and experiments. Our key
      result is that an asymmetric distribution of membrane accounts for approximately
      one-half of the measured amplification from ligand concentration to PIP3
      production. We also show that the underlying biochemical network behaves as a
      linear amplifier in the micropipette assay.

PMID- 17021384
TI  - Stochastic model of transcription factor-regulated gene expression.
AB  - We consider a stochastic model of transcription factor (TF)-regulated gene
      expression. The model describes two genes, gene A and gene B, which synthesize
      the TFs and the target gene proteins, respectively. We show through analytic
      calculations that the TF fluctuations have a significant effect on the
      distribution of the target gene protein levels when the mean TF level falls in
      the highest sensitive region of the dose-response curve. We further study the
      effect of reducing the copy number of gene A from two to one. The enhanced TF
      fluctuations yield results different from those in the deterministic case. The
      probability that the target gene protein level exceeds a threshold value is
      calculated with the knowledge of the probability density functions associated
      with the TF and target gene protein levels. Numerical simulation results for a
      more detailed stochastic model are shown to be in agreement with those obtained
      through analytic calculations. The relevance of these results in the context of
      the genetic disorder haploinsufficiency is pointed out. Some experimental
      observations on the haploinsufficiency of the tumour suppressor gene, Nkx 3.1,
      are explained with the help of the stochastic model of TF-regulated gene
      expression.

PMID- 17021385
TI  - Contribution of whole-cell optimization via cell body rolling to polarization of
      T cells.
AB  - Directed secretion of cytotoxins or cytokines by T cells during immune response
      depends on migration of the centrosome in the T cell to the interface with the
      target cell. The mechanism of the centrosome translocation has been elusive. The
      presented computational analysis demonstrates that the centrosome should be
      positioned at the interface if the T cell attempts simultaneously (a) to minimize
      its surface area, (b) to maximize the interface area, (c) to maintain the cell
      volume and (d) to straighten the microtubules. Live three-dimensional microscopy
      and measurements show that the optimal position of the centrosome is achieved in
      large part (by about 40%) via rolling of the entire T cell body on the target
      surface; this movement appears to entrain the centrosome. The theoretical and
      experimental results draw attention to the previously unrecognized role of the
      whole-cell structure and whole-cell movements in the T cell polarization.

PMID- 17021386
TI  - On the use of magnets to disrupt the physiological compass of birds.
AB  - Behavioral researchers have attached magnets to birds during orientation
      experiments, assuming that such magnets will disrupt their ability to obtain
      magnetic information. Here, we investigate the effect of an attached magnet on
      the ability to derive directional information from a radical-pair based compass
      mechanism. We outline in some detail the geometrical symmetries that would allow
      a bird to identify magnetic directions in a radical-pair based compass. We show
      that the artificial field through an attached magnet will quickly disrupt the
      birds' ability to distinguish pole-ward from equator-ward headings, but that much
      stronger fields are necessary to disrupt their ability to detect the magnetic
      axis. Together with estimates of the functional limits of a radical-pair based
      compass, our calculations suggest that artificial fields of comparable size to
      the geomagnetic field are not generally sufficient to render a radical-pair based
      compass non-functional.

PMID- 17021387
TI  - Cancer-testis antigens in tumor biology and immunotherapy.

PMID- 17021388
TI  - Antidepressant-like properties of the anti-Parkinson agent, piribedil, in
      rodents: mediation by dopamine D2 receptors.
AB  - The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist,
      piribedil, is used clinically as monotherapy and as an adjunct to L-3,4
      dihydroxyphenylalanine in the treatment of Parkinson's disease. As it appears to
      improve mood, we examined its actions in rodent models of antidepressant
      properties, in comparison with the prototypical anti-Parkinson agent,
      apomorphine, the D2/D3 receptor agonist, quinpirole, and the antidepressants,
      imipramine and fluvoxamine. In the mouse forced-swim test, acute administration
      of imipramine, fluvoxamine, apomorphine or quinpirole decreased immobility time,
      actions dose dependently mimicked by piribedil (2.5-10.0 mg/kg, subcutaneously).
      In rats, acute and subchronic administration of piribedil similarly reduced
      immobility (0.63-10.0 mg/kg, subcutaneously) and apomorphine, quinpirole and
      imipramine were also active in this test, whereas fluvoxamine was inactive. Both
      in mice and in rats, the D2/D3 receptor antagonist, raclopride, and the D2
      receptor antagonist, L741,626, dose dependently blocked the antidepressant
      properties of piribedil, whereas the selective D3 receptor antagonists, S33084
      and SB277,011, were ineffective. In a chronic mild stress model in rats,
      piribedil (2.5-40.0 mg/kg, subcutaneously) restored sucrose intake in stressed
      animals exerting its actions more rapidly (by week 1) than imipramine.
      Imipramine, fluvoxamine, apomorphine, quinpirole and piribedil dose dependently
      (0.63-10.0 mg/kg, subcutaneously) suppressed aggressive and marble-burying
      behaviour in mice. In the latter procedure, raclopride and L741,626, but not
      S33084, attenuated the actions of piribedil. Over a dose range (0.63-10.0 mg/kg,
      subcutaneously) equivalent to those active in models of antidepressant activity,
      piribedil did not stimulate locomotor behaviour. In conclusion, principally via
      recruitment of D2 receptors, piribedil exerts robust and specific antidepressant
      like actions in diverse rodent models.

PMID- 17021389
TI  - The effects of chronic administration of ethosuximide on learning and memory: a
      behavioral and biochemical study on nonepileptic rats.
AB  - Long-term use of antiepileptic drugs is common in the treatment of epilepsy.
      Clinical reports exist of cognitive impairment attributed to antiepileptic drugs.
      Hence, this study evaluates the effect of chronic administration of one
      antiepileptic drug, ethosuximide, on spatial and fear learning and memory in
      nonepileptic rats. High performance liquid chromatography with electrochemical
      detection was used for quantification of glutamate, glycine, taurine, gamma
      aminobutyric acid, dopamine, and serotonin in the frontal cortex and hippocampus
      to elucidate the neurobiological basis of the effect of ethosuximide on learning
      and memory. We found that 21 days of ethosuximide treatment produced negative
      effects on fear memory (passive avoidance) at all doses (100, 200 and 250 mg/kg
      body weight), but had no effect on spatial learning (T-maze). Fear memory
      impairment was associated with decreased hippocampal dopamine levels.
      Ethosuximide (at all doses) had a minimal effect on the GABAergic and
      glutamatergic systems in all brain regions studied, with the exception of
      elevated levels of gamma-aminobutyric acid in the frontal cortex with the 250
      mg/kg body weight dose. We have shown that long-term administration of
      ethosuximide adversely affects fear memory, but does not affect spatial learning
      and memory.

PMID- 17021390
TI  - Modeling anxiety-like states: pharmacological characterization of the chick
      separation stress paradigm.
AB  - While previous research has sought to validate the chick separation stress
      paradigm as an anxiolytic screening assay, it is unknown whether the paradigm
      better models a nonspecific anxiety-like state or something similar to panic
      disorder or generalized anxiety disorder. To characterize the anxiety model
      pharmacologically, cockerels were administered drug probes that were either: (1)
      only effective for treating panic disorder (phenelzine 3.125-25.0 mg/kg), (2)
      effective for treating both panic disorder and generalized anxiety disorder
      (alprazolam 0.065-0.5 mg/kg; clonidine 0.1-0.25 mg/kg; imipramine 1.0-15.0
      mg/kg), (3) only effective for treating generalized anxiety disorder (buspirone
      2.5-10.0 mg/kg; trazodone 0.1-3.0 mg/kg) or (4) capable of exacerbating symptoms
      of panic disorder in humans (yohimbine 0.1-3.0 mg/kg). At 7 days after hatch,
      chicks received either vehicle or drug probe intramuscularly 15 min prior to
      social separation under a mirror (low-stress) or no-mirror (high-stress)
      condition for a 180-s observation period. Dependent measures were distress
      vocalizations to index separation stress and sleep-onset latency to index
      sedation. Phenelzine, alprazolam, imipramine and clonidine were able to attenuate
      distress vocalizations (at doses without significant sedation) whereas buspirone
      and trazodone did not. Paradoxically, yohimbine modestly attenuated distress
      vocalizations. These results suggest that the chick separation stress paradigm
      better models panic disorder than generalized anxiety disorder as an anxiolytic
      screen.

PMID- 17021391
TI  - Involvement of dorsolateral periaqueductal gray N-methyl-D-aspartic acid
      glutamate receptors in the regulation of risk assessment and inhibitory avoidance
      behaviors in the rat elevated T-maze.
AB  - The involvement of the dorsolateral periaqueductal gray in the regulation of fear
      related behaviors such as escape and freezing is well established. It is still a
      matter of investigation, however, whether this midbrain area may have a relevant
      role in the modulation of more subtle defensive responses associated with anxiety
      such as risk assessment and inhibitory avoidance. By stimulating N-methyl-D
      aspartic acid glutamate receptors located in the dorsolateral periaqueductal gray
      with its prototypical agonist N-methyl-D-aspartic acid (50 pmol), we report here
      an increase in both risk assessment and inhibitory avoidance behaviors of male
      Wistar rats tested in the elevated T-maze. These results are indicative of an
      anxiogenic-like effect. The selective N-methyl-D-aspartic acid receptor
      antagonist DL-2-amino-7-phosphonoheptanoic acid (2.0 and 4.0 nmol) had the
      opposite effect on both defensive tasks. Pretreatment with an ineffective dose of
      DL-2-amino-7-phosphonoheptanoic acid (1.0 nmol) prevented the N-methyl-D-aspartic
      acid anxiogenic-like effect. At the dose range of DL-2-amino-7-phosphonoheptanoic
      acid and/or N-methyl-D-aspartic acid tested, neither the escape response from one
      of the elevated T-maze open arms nor the general exploratory activity as assessed
      in the open-field test was affected. The present results suggest that the
      dorsolateral periaqueductal gray column is also involved in the regulation of
      defensive behaviors related to anxiety, and N-methyl-D-aspartic acid glutamate
      receptors are recruited for this action.

PMID- 17021392
TI  - Effects of environmental enrichment on extinction and reinstatement of
      amphetamine self-administration and sucrose-maintained responding.
AB  - The current experiments aimed to determine whether differential rearing alters
      extinction and/or reinstatement of amphetamine self-administration or sucrose
      maintained responding. Male Sprague-Dawley rats were raised in either an enriched
      condition or an isolated condition. Rats were then trained to lever press on a
      continuous reinforcement schedule across either 15 daily amphetamine self
      administration sessions or 15 sucrose-reinforced sessions, followed by 10
      sessions of extinction. After the extinction sessions, priming doses of
      amphetamine (0, 0.25 or 1.0 mg/kg) were administered 15 min before the session,
      or sucrose (one or 10 pellets) was delivered non-contingently at the beginning of
      the session. Enriched condition rats showed greater extinction for amphetamine
      and sucrose-maintained responding than isolated condition rats. When primed with
      amphetamine, isolated condition rats reinstated responding following 0.25 mg/kg
      of amphetamine, whereas enriched condition rats only reinstated responding after
      1.0 mg/kg of amphetamine. Isolated condition rats failed to reinstate responding
      following sucrose delivery, while enriched condition rats reinstated responding
      following the delivery of 10 sucrose pellets. These results indicate that
      environmental enrichment enhanced the extinction of both amphetamine and sucrose
      maintained responding. Environmental enrichment also raised the reinstatement
      threshold specific to the amphetamine prime, suggesting a reduction in the
      incentive motivational effect of amphetamine.

PMID- 17021393
TI  - Two-choice reaction time performance in Sprague-Dawley rats exposed to alcohol
      during adolescence or adulthood.
AB  - Adolescent alcohol abusers display subtle attention impairments. This study used
      a two-choice reaction time task to examine the effects of ethanol on sustained
      attention following adult or adolescent exposure. Sprague-Dawley rats were
      exposed to ethanol vapor for 14 days starting on postnatal day 30 (adolescence)
      or 60-64 (adulthood) and were then trained to perform the two-choice reaction
      time task. Ethanol exposure resulted in blood ethanol levels averaging 215 mg/dl.
      Behavior following adult ethanol exposure was characterized by increased accuracy
      and omissions during the two-choice reaction time task, reduced fixed ratio lever
      pressing, and reductions in the highest fixed ratio completed on a progressive
      ratio schedule. Adolescent ethanol exposure transiently increased two-choice
      reaction time accuracy and slightly reduced fixed ratio lever presses. Improved
      accuracy was unexpected, but might be related to ethanol-induced increases in
      central nervous system arousal and/or mild behavioral perseveration. Increased
      omissions, reduced lever pressing, and reductions in the highest fixed ratios
      completed most likely reflect decreased 'motivation to work' and index
      generalized anhedonia. This study is the first to demonstrate that rats exposed
      to ethanol during adulthood are more sensitive to the effects of ethanol on
      sustained attention than rats exposed to ethanol during adolescence and to
      ethanol-induced anhedonia, as indexed by two-choice reaction time performance.

PMID- 17021394
TI  - Catha edulis extract and its active principle cathinone induce ipsilateral
      rotation in unilaterally lesioned rats.
AB  - Catha edulis extract, a natural psychostimulant, and its active component, S-(-)
      cathinone, were evaluated for their rotational effects in unilaterally lesioned
      rats. In our earlier study, we demonstrated that commercially available S-(-)
      cathinone, the active principle of C. edulis extract, reverses haloperidol
      induced catalepsy. In the current study, we evaluated the effect of C. edulis
      extract or its active principle, cathinone, in 6-hydroxydopamine unilaterally
      lesioned rats. Evaluation of the rotational behaviour induced by this natural
      psychostimulant was made upon acute and repeated oral administration. The data
      show that C. edulis extract or S-(-)-cathinone induced ipsilateral rotation in 6
      hydroxydopamine unilaterally lesioned rats. The ipsilateral rotation produced by
      commercially available S-(-)-cathinone was more marked than the response produced
      by oral administration of lyophilized C. edulis extract at the dose and periods
      specified. In addition, upon repeated administration, the effect was more
      pronounced (i.e. there was sensitization). In conclusion, the results demonstrate
      that the plant induces ipsilateral rotation, like its close relative amphetamine.

PMID- 17021395
TI  - Theophylline inhibits tolerance and sensitization induced by morphine: a
      conditioned place preference paradigm study in female mice.
AB  - The effect of theophylline on reward properties of morphine was examined in the
      present study. A biased conditioned place preference paradigm was used to study
      the effects of theophylline on the development of conditioned place preference by
      morphine in sensitized and tolerant female mice. Subcutaneous injection of
      morphine (0.5-10 mg/kg) induced conditioned place preference in mice, while
      intraperitoneal administration of theophylline (2.5-100 mg/kg) did not induce
      conditioned place preference or conditioned place aversion. Theophylline (2.5-100
      mg/kg) in combination with morphine (5 mg/kg), during conditioning sessions,
      decreased the acquisition of morphine conditioned place preference dose
      independently. Administration of theophylline (2.5-100 mg/kg) before testing also
      caused a significant reduction of the expression of morphine-induced conditioned
      place preference in a dose-independent manner. Administration of morphine (12.5,
      25 or 50 mg/kg) daily, for 3 days, produced tolerance to conditioned place
      preference induced by the drug (5 mg/kg). Administration of theophylline (2.5 and
      10 mg/kg) 1 h before morphine (12.5, 25 mg/kg), during development of tolerance,
      abolished morphine tolerance. A higher dose of theophylline (100 mg/kg), however,
      did not alter morphine tolerance. In addition, theophylline (2.5, 10 and 100
      mg/kg) failed to reduce tolerance to a higher dose of morphine (50 mg/kg). Daily
      administration of morphine (5 mg/kg) for 3 days followed by a 5-day interval
      caused sensitization to morphine place conditioning. When theophylline was
      administered (2.5, 10 and 100 mg/kg) 1 h before morphine (5 mg/kg), during
      development of sensitization, inhibition of morphine-induced sensitization was
      demonstrated. The effect of theophylline was dose independent. It is concluded
      that while theophylline has no effect by itself, it reduced both the acquisition
      and expression of morphine conditioned place preference. In addition,
      theophylline reduced the acquisition of morphine conditioned place preference in
      morphine-sensitized and morphine-tolerant mice.

PMID- 17021396
TI  - Effects of ultra-low doses of nicotine on the expression of morphine-induced
      conditioned place preference in mice.
AB  - In the present study, the effects of acute administration of nicotine, as well as
      nicotinic and muscarinic acetylcholine receptor antagonists, on the expression of
      morphine-induced conditioned place preference, have been investigated in male
      Swiss-Webster mice. Animals received different doses of morphine 5 days after
      surgical cannulation in the lateral ventricle. Subcutaneous injections of
      morphine (2-5 mg/kg) in mouse produced place preference in a dose-dependent
      manner. Furthermore, both intraperitoneal (0.0006-0.1 mg/kg) and
      intracerebroventricular (0.007-25 ng) nicotine administration significantly
      reduced the expression of morphine-induced place preference, in a dose-dependent
      manner. Nicotine, however, was effective over narrow ultra-low dose ranges
      (0.0012, 0.0025, 0.005 and 0.01 mg/kg; intraperitoneal) and (0.03, 0.1, 0.3 and
      0.6 ng/mouse; intracerebroventricular). In addition, locomotor activity was
      reduced when higher doses of nicotine [both intraperitoneal (0.02, 0.03 and 0.1
      mg/kg) and intracerebroventricular (10 and 24 ng/mouse)] were used. Nicotine
      alone, however, did not cause motivational effects. Intracerebroventricular
      injection of hexamethonium (0.03, 0.1 and 0.3 mug/mouse; 10 min before nicotine)
      diminished the effects of nicotine on morphine-induced conditioned place
      preference. This effect could neither be obtained by intraperitoneal
      administration of hexamethonium (1, 5 and 10 mg/kg; 30 min before nicotine), nor
      be reproduced after either intracerebroventricular or intraperitoneal injection
      of atropine (a muscarinic receptor antagonist). The antagonists, themselves, did
      not show any motivational effects when used alone and were unable to affect the
      expression of morphine-induced conditioned place preference. It appears that
      ultra-low doses of nicotine can reduce the expression of morphine-induced place
      preference, and that central nicotinic acetylcholine receptors play a role in
      this regard.

PMID- 17021397
TI  - Role of serotonin type 1A receptors in fluvoxamine-induced inhibition of marble
      burying behavior in mice.
AB  - This study examined the roles of presynaptic and postsynaptic serotonin type 1A
      receptors in fluvoxamine-induced inhibition of marble-burying behavior in mice.
      The effect of fluvoxamine was attenuated by the serotonin type 1A receptor
      antagonist WAY100635 at 1 mg/kg, while it was enhanced by the antagonist at 0.1
      mg/kg. Fluvoxamine (30 mg/kg) and WAY100635 (0.1 and 1 mg/kg) did not affect
      spontaneous locomotor activity. These results suggest that the effect of
      fluvoxamine is mediated by postsynaptic serotonin type 1A receptors and it is
      enhanced by an inhibition of presynaptic serotonin type 1A receptors.

PMID- 17021398
TI  - Immunohistochemical analysis of metastatic neoplasms of the central nervous
      system.
AB  - Metastatic neoplasms to the central nervous system are often encountered in the
      practice of surgical neuropathology. It is not uncommon for patients with
      systemic malignancies to present to medical attention because of symptoms from a
      brain metastasis and for the tissue samples procured from these lesions to
      represent the first tissue available to study a malignancy from an unknown
      primary. In general surgical pathology, the evaluation of a metastatic neoplasm
      of unknown primary is a very complicated process, requiring knowledge of numerous
      different tumor types, reagents, and staining patterns. The past few years,
      however, have seen a remarkable refinement in the immunohistochemical tools at
      our disposal that now empower neuropathologists to take an active role in
      defining the relatively limited subset of neoplasms that commonly metastasize to
      the central nervous system. This information can direct imaging studies to find
      the primary tumor in a patient with an unknown primary, clarify the likely
      primary site of origin in patients who have small tumors in multiple sites
      without an obvious primary lesion, or establish lesions as late metastases of
      remote malignancies. Furthermore, specific treatments can begin and additional
      invasive procedures may be prevented if the neuropathologic evaluation of
      metastatic neoplasms provides information beyond the traditional diagnosis of
      "metastatic neoplasm." In this review, differential cytokeratins, adjuvant
      markers, and organ-specific antibodies are described and the immunohistochemical
      signatures of metastatic neoplasms that are commonly seen by neuropathologists
      are discussed.

PMID- 17021399
TI  - Opioid preconditioning induces opioid receptor-dependent delayed neuroprotection
      against ischemia in rats.
AB  - We have shown that exposure of neurons to opioid immediately before ischemia
      induces ischemia tolerance. This phenomenon is called acute opioid
      preconditioning. In this study, we test the hypothesis that opioids induce
      delayed neuropreconditioning (from hours to days after opioid exposure). Exposure
      to morphine, an agonist for delta-, mu-, and kappa-opioid receptors, or Tan-67, a
      selective delta1-receptor agonist, for 30 minutes at 24 hours before a 35-minute
      oxygen-glucose deprivation (OGD, to simulate ischemia in vitro) dose-dependently
      reduced the OGD-induced neuronal death in the CA1 region of the rat organotypic
      hippocampal slice cultures. The morphine preconditioning-induced neuroprotection
      was inhibited by beta-funaltrexamine, a mu-opioid receptor antagonist, but not by
      7-benzylidenenaltrexone, a delta1-receptor antagonist, or nor-binaltorphimine, a
      kappa-receptor antagonist. The Tan-67 preconditioning-induced neuroprotection was
      inhibited by 7-benzylidenenaltrexone. The combination of morphine and Tan-67 did
      not induce a better preconditioning effect than did morphine or Tan-67 alone.
      Application of morphine and Tan-67 at 24 hours before permanent right middle
      cerebral arterial occlusion reduced brain infarct volume and improved neurologic
      functional outcome assessed 24 hours after the occlusion in adult male rats.
      These results suggest that morphine and Tan-67 induce a delayed preconditioning
      effect in the brain under in vivo and in vitro conditions. Whereas the delayed
      phase of morphine preconditioning may involve mu-opioid receptors, Tan-67
      preconditioning may be mediated by delta1-opioid receptors. Morphine and Tan-67
      may activate a shared intracellular signaling pathway to induce the delayed
      preconditioning effects in the brain.

PMID- 17021400
TI  - LRRK2 expression in normal and pathologic human brain and in human cell lines.
AB  - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently
      identified in families with autosomal-dominant late-onset Parkinson disease. We
      report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2
      is expressed in soluble extracts of human brain, liver, and heart and in cultured
      human astrocytes, microglia, and oligodendroglia as well as in human
      neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody
      of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal
      residues 2,511-2,527 that an apparent full-length protein and several of its
      fractions are expressed in soluble extracts of normal human brain. By
      immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes
      and microglia, in normal brain tissue. It intensely labels Lewy bodies in
      Parkinson disease and related neurodegenerative disorders. It also labels a
      subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism
      dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and
      oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple
      system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions
      in Huntington disease; and intraneuronal and glial inclusions in amyotrophic
      lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and
      also in glial cells of human brain. It strongly associates with pathological
      inclusions in several neurodegenerative disorders.

PMID- 17021401
TI  - Adenosine A1 receptor protein levels and activity is increased in the cerebral
      cortex in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy
      infected bovine-PrP mice.
AB  - Prion diseases are characterized by neuronal loss, astrocytic gliosis, spongiform
      change, and abnormal protease-resistant prion protein (PrP) deposition.
      Creutzfeldt-Jakob disease (CJD) is the most prevalent human prion disease,
      whereas scrapie and bovine spongiform encephalopathy (BSE) are the most common
      animal prion diseases. Several candidates have been proposed as mediators of
      degeneration in prion diseases, one of them glutamate. Recent studies have shown
      reduced metabotropic glutamate receptor/phospholipase C signaling in the cerebral
      cortex in CJD, suggesting that this important neuromodulator and neuroprotector
      pathway is attenuated in CJD. Adenosine is involved in the regulation of
      different metabolic processes under physiological and pathologic conditions.
      Adenosine function is mediated by adenosine receptors, which are categorized into
      4 types: A1, A2A, A2B, and A3. A1Rs are G-protein-coupled receptors that induce
      the inhibition of adenylyl cyclase activity. The most dramatic inhibitory actions
      of adenosine receptors are on the glutamatergic system. For these reasons, we
      examined the levels of A1Rs in the frontal cortex of 12 patients with CJD and 6
      age-matched controls and in BSE-infected bovine-PrP transgenic mice (BoPrP-Tg110
      mice) at different postincubation times to address modifications in A1Rs with
      disease progression. A significant increase in the protein levels of A1Rs was
      found in the cerebral cortex in CJD and in the murine BSE model at advanced
      stages of the disease and coincidental with the appearance of PrP expression. In
      addition, the activity of A1Rs was analyzed by in vitro assays with isolated
      membranes of the frontal cortex in CJD. Increased activity of the receptor, as
      revealed by the decreased forskolin-stimulated cAMP production in response to the
      A1R agonists cyclohexyl adenosine and cyclopentyl adenosine, was observed in CJD
      cases when compared with controls. Finally, mRNA A1R levels were similar in CJD
      and control cases, thus suggesting abnormal A1R turnover or dysregulation of raft
      associated signaling pathways in CJD. These results show, for the first time,
      sensitization of A1Rs in prion diseases.

PMID- 17021402
TI  - Plaque-associated overexpression of insulin-degrading enzyme in the cerebral
      cortex of aged transgenic tg2576 mice with Alzheimer pathology.
AB  - It was proposed that insulin-degrading enzyme (IDE) participates in the clearance
      of amyloid beta (Abeta) in the brain, and its low expression or activity may be
      relevant for the progression of Alzheimer disease. We performed a longitudinal
      study of brain level, activity, and distribution of IDE in transgenic mice
      (Tg2576) expressing the Swedish mutation in human Abeta precursor protein. At 16
      months of age, Tg2576 showed a significant 2-fold increment in IDE protein level
      as compared with 4.5- and 11-month-old animals. The peak of IDE was in synchrony
      with the sharp accumulation of sodium dodecyl sulfate-soluble Abeta and massive
      Abeta deposition into plaques. At this stage, IDE appeared surrounding Abeta
      fibrillar deposits within glial fibrillar acidic protein-positive astrocytes,
      suggesting that it was locally overexpressed during the Abeta-mediated
      inflammation process. When primary astrocytes were exposed to fibrillar Abeta in
      vitro, IDE protein level increased as compared with control, and this effect was
      reduced by the addition of U0126, a specific inhibitor of the ERK1/2 mitogen
      activated protein kinase cascade. We propose that in Tg2576 mice and in contrast
      to its behavior in Alzheimer brains, active IDE increases with age around plaques
      as a component of astrocyte activation as a result of Abeta-triggered
      inflammation.

PMID- 17021403
TI  - Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests
      mechanism of concurrent 1p and 19q loss.
AB  - Deletions of portions of chromosomes 1p and 19q are closely associated with the
      oligodendroglioma histologic phenotype. In most cases, 1p and 19q are codeleted,
      yet the mechanism of dual loss is unexplained. We report 5 cases (World Health
      Organization grade III) in which metaphase cytogenetics identified a derivative
      chromosome consisting of what appears to be the whole arms of 1q and 19p forming
      a der(1;19)(q10;p10). Metaphase fluorescent in situ hybridization (FISH)
      confirmed the derivative chromosome was composed of 1q and 19p material in 3
      cases; in 2 cases with few metaphases, FISH confirmed 19p material on the
      derivative chromosome. In all cases, interphase FISH showed net loss of 1p and
      19q in 77% to 92% of cells, and microsatellite studies were consistent with 1p
      and 19q loss. We hypothesize the following: occurrence of a balanced whole-arm
      translocation between chromosomes 1 and 19 forming 2 derivative chromosomes, one
      composed of 1q and 19p, the other of 1p and 19q. Subsequent loss of the
      der(1;19)(p10;q10) then results in the simultaneous 1p and 19q loss observed in
      oligodendroglioma with retention of the der(1;19)(q10;p10) seen in these cases.

PMID- 17021404
TI  - Limb-girdle muscular dystrophy in the United States.
AB  - Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7
      autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To
      determine the distribution of subtypes among patients in the United States, 6
      medical centers evaluated patients with a referral diagnosis of LGMD. Muscle
      biopsies provided histopathology and immunodiagnostic testing, and their protein
      abnormalities along with clinical parameters directed mutation screening. The
      diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289
      unrelated patients, 266 had muscle biopsies sufficient for complete microscopic
      evaluation; 121 also underwent Western blotting. From this combined evaluation,
      the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy,
      15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes
      distributed among 2 dominant and 7 recessive subtypes have been determined for 83
      patients. This study of a large racially and ethnically diverse population of
      patients with LGMD indicates that establishing a putative subtype is possible
      more than half the time using available diagnostic testing. An efficient approach
      to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed
      mutational analysis. The most common LGMDs in the United States are
      calpainopathies, dysferlinopathies, sarcoglycanopathies, and
      dystroglycanopathies.

PMID- 17021405
TI  - Prognosis and histopathologic features in papillary tumors of the pineal region:
      a retrospective multicenter study of 31 cases.
AB  - Papillary tumor of the pineal region (PTPR) is a recently described tumor entity
      thought to arise from the specialized ependyma of the subcommissural organ.
      Whereas histologic features of PTPR are well defined, data on the prognostic
      value of PTPR remain scarce. We therefore investigated clinicopathologic
      features, including data on progression-free survival and overall survival, in a
      retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged
      from 5 to 66 years (median age, 29 years). Histologically, all tumors were
      characterized by an epithelial-like growth pattern in which the vessels were
      covered by layers of columnar or cuboidal tumor cells forming perivascular
      pseudorosettes. Most of the tumor cells showed strong expression of neuron
      specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin.
      Most PTPRs examined also expressed microtubule-associated protein-2. Expression
      of synaptophysin, epithelial membrane antigen, transthyretin, neural cell
      adhesion molecule, and nestin was encountered in some tumors. Gross total
      resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy
      on resection of the primary tumor. Nevertheless, the majority of patients
      experienced recurrences; 5-year estimates for overall survival and progression
      free survival were 73% and 27%, respectively. To conclude, the clinical course of
      PTPR is characterized by frequent local recurrence, and the value of radiotherapy
      on disease progression will need to be investigated in future prospective trials.

PMID- 17021406
TI  - Decreased expression and activity of neprilysin in Alzheimer disease are
      associated with cerebral amyloid angiopathy.
AB  - Neprilysin (NEP) degrades amyloid-beta (Abeta) and is thought to contribute to
      its clearance from the brain. In Alzheimer disease (AD), downregulation of NEP
      has been suggested to contribute to the development of cerebral amyloid
      angiopathy (CAA). We examined the relationship among NEP, CAA, and APOE status in
      AD and elderly control cases. NEP was most abundant in the tunica media of
      cerebrocortical blood vessels and in pyramidal neurons. In homogenates of the
      frontal cortex, NEP protein levels were reduced in AD but not significantly; NEP
      enzymatic activity was significantly reduced in AD. Immunohistochemistry revealed
      a reduction of both vascular and parenchymal NEP. The loss of vessel-associated
      NEP in AD was inversely related to the severity of CAA, and analysis of cases
      with severe CAA showed that levels of vascular NEP were reduced to the same
      extent in Abeta-free and Abeta-laden vessels, strongly suggesting that the
      reduction in NEP is not simply secondary to CAA. Possession of APOE epsilon4 was
      associated with significantly lower levels of both parenchymal and vascular NEP.
      Colinearity of epsilon4 with the presence of moderate to severe CAA precluded
      assessment of the independence of this association from NEP levels. However,
      logistic regression analysis showed low NEP levels to be a significant
      independent predictor of moderate to severe CAA.

PMID- 17021407
TI  - Latency of alpha-herpes viruses is accompanied by a chronic inflammation in human
      trigeminal ganglia but not in dorsal root ganglia.
AB  - The immune response to latent herpesvirus infections was compared in human
      trigeminal ganglia (TG) and dorsal root ganglia (DRG) of 15 dead individuals. On
      the basis of our previous findings, we hypothesized that T-cells would be
      attracted to sensory neurons latently infected with herpes simplex virus type 1
      (HSV-1), but not to those harboring latent varicella zoster virus (VZV). We
      showed that the TG contain a positive hybridization signal for HSV-1 latency
      associated transcript (LAT), whereas the DRG from the same individuals lack
      detectable LAT. In contrast, immunohistochemistry revealed that latent VZV
      protein 62 stained positive in the vast majority of all tested TG and DRG. T-cell
      infiltrates prominently surrounded individual neurons in the TG but not in the
      DRG. TaqMan polymerase chain reaction also showed higher expression of CD8 and
      RANTES transcripts in the TG versus DRG. Only the infiltrates in the TG, but not
      in the DRG, produced RANTES at the protein level. Because it has been shown that
      RANTES protein is produced only after T-cell receptor stimulation, we assume that
      T-cell infiltration is associated with antigen recognition in the TG but not in
      the DRG.

PMID- 17021408
TI  - Early clinical and radiologic outcomes of cervical arthroplasty with Bryan
      Cervical Disc prosthesis.
AB  - Among 61 patients underwent disc replacement with the Bryan prosthesis, 47
      patients were followed more than 3 months and their clinical and radiologic data
      were retrospectively analyzed to clarify very early clinical and radiologic
      outcomes and complications of disc arthroplasty with the Bryan Cervical Disc
      prosthesis during the learning period. Mean follow-up period was 6 months. Mean
      age was 45.6 years. Single-level procedure was done in 39 patients and 2-level in
      8; a total of 55 levels replaced. Neck disability index improved from 59.8% to
      22.9%. Visual analog pain score (VAS) of the neck improved from 8.4 to 1.6. VAS
      of shoulder/arm pain improved from 8.8 to 2.4. Mean patients' subjective
      improvement rate of symptoms was 71.1%. According to improvement in the neck
      disability index and VAS (over 50% improvement rate in each parameter), patients'
      subjective improvement rate (over 50%), and patients' satisfaction, the surgical
      success was achieved in 39 patients (83%). Eight patients (17%) showed failure.
      Mean segmental angle became more kyphotic after surgery from -0.7 degree of
      kyphosis (-11 to 7.7 degrees) to -1.3 degrees (-32 to 20.9 degrees) without
      statistical significance (P=0.55). Among 24 segments that showed preoperative
      kyphosis, 13 (54.2%) showed aggravated kyphosis, 7 (29.1%) showed decreased
      kyphosis and 4 (16.7%) recovered to lordosis. Among 31 segments that showed
      preoperative lordosis, 19 (61.3%) showed loss of lordosis and 12 (38.7%) showed
      increased lordosis. Mean range of motion increased significantly after surgery
      (6.7 to 8.5 degrees, P=0.04). Preoperative and postoperative segmental kyphosis
      was not related to clinical success. Cervical arthroplasty with the Bryan
      Cervical Disc prosthesis failed to restore segmental lordotic angle. A concern
      arises because it is well known that the fusion in kyphotic curvature causes more
      frequent problems on adjacent levels in anterior cervical discectomy and fusion.
      For the present, it seems preferable to exclude the patient who already has
      significant segmental kyphosis from disc arthroplasty with Bryan Cervical Disc
      prosthesis.

PMID- 17021409
TI  - Video-assisted ALIF with cage and anterior plate fixation for L5-S1
      spondylolisthesis.
AB  - INTRODUCTION: Spondylolysis and spondylolisthesis grade 0, 1, and 2 are mainly
      asymptomatic but with aging process and different factors some back pain can
      occur and lead to chronic low back pain. The conservative treatment with
      physiotherapy and steroid injection is the gold standard but in some cases is not
      efficient enough and a surgical treatment is proposed. OBJECTIVES: The goal of
      this study is to propose a new technique to treat grade 0, 1, and 2
      spondylolisthesis with an anterior video-assisted fusion and stabilization.
      METHODS: Twenty patients with chronic low back pain since more than 2 years and
      resistant to conservative therapy were included in this protocol. Clinical signs
      and radicular pain were noted. They were evaluated preoperatively and
      postoperatively until the last follow up using Oswestry score and visual analog
      score (VAS) for leg and back pain. X-rays showed grade 0 (8 cases), 1 (10 cases),
      and 2 (2 cases) spondylolisthesis according to Meyerding classification with disc
      collapse (bulging disc). MRI showed in all cases a disc degeneration with at
      least black disc and/or endplates changes with Modic I or II. All patients were
      operated using an anterior video-assisted retroperitoneal approach, with
      discectomy and fusion using an anterior impacted cage filled with autologous
      cancellous bone from the iliac crest and an anterior fixation with a triangular
      plate (Pyramid, Medtronic, Memphis). The follow up at 3, 6, 12, and 24 months was
      done with clinical and radiologic evaluation. In case of problem a computed
      tomography scan was performed. RESULTS: There were 11 women and 9 men, with and
      average age of 39 years old and a BMI of 25.6. All spondylolistheses occurred at
      level L5. The average slippage was 19%. All L5S1 discs were black, 8 had a Modic
      I changes in the endplates and 2 had Modic II. The shape of L5 vertebra was
      abnormal (trapezoidal) in 7 cases. All anterior approaches were performed without
      vascular, urologic, or digestive complication. Blood loss was inferior to 100 mL.
      All patients had a soft brace for 8 weeks postoperatively. There was no
      retrograde ejaculation for the 9 men and no sexual dysfunction reported by the
      women. One patient had no pain relief and was reoperated for posterior pedicular
      screw fixation. It was obvious that there was a pseudarthrosis even after the
      posterior fixation and an anterior transperitoneal revision was performed with
      the removal of the interbody device and iliac crest bone graft packing alone. A
      propioni bacterium acnes germ was found responsible for the anterior nonunion.
      This revision surgery with antibiotics treatment was successful. One of the
      patients with grade 2 had an additional posterior screw fixation with a minimally
      invasive pedicle screw system (Sextant, Medtronic, Memphis). Nineteen patients
      had a good fusion at 2 years follow-up (95%), mean Oswestry score improved from
      74% preoperative to 21% postoperative at the last follow-up. Visual analog score
      (VAS) for back pain improved from 6.5 to 2.7 and VAS for leg pain improved from
      6.2 to 3.4. Satisfaction rate was 90%. All active patients except two, were back
      to work at an average of 5.5 months (6 wk to 1 y). The 2 patients still not
      working were the nonunion and a work compensation. CONCLUSIONS: The results of
      this technique compare favorably with posterior stabilization and fusion
      (posterior lumbar interbody fusion and postero-lateral fusion) reported in the
      literature. Unlike posterior lumbar interbody fusion, however, it seems that the
      complication rate due to the approach is much lower, the fusion rate is similar.
      Grade 2 SPL is the limitation of the technique. The main advantage of the
      technique is to avoid posterior muscle damage and a quick recovery with no blood
      loss. Preservation of adjacent level disease can be assessed only after long-term
      follow-up.

PMID- 17021410
TI  - Agreement between orthopedic surgeons and neurosurgeons regarding a new algorithm
      for the treatment of thoracolumbar injuries: a multicenter reliability study.
AB  - INTRODUCTION: Considerable variability exists in the management of thoracolumbar
      (TL) spine injuries. Although there are many influences, one significant factor
      may be the treating surgeon's specialty and training (ie, orthopedic surgery vs.
      neurosurgery). Our objective was to assess the agreement between spinal
      orthopedic and neurologic surgeons in rating the severity of TL spine injuries
      with a new treatment algorithm. This information could be important in
      establishing consensus-based protocols for managing these challenging injuries.
      METHODS: Twenty-eight spinal surgeons (8 neurosurgeons and 20 orthopedic
      surgeons) reviewed 56 TL injury case histories. Each case was classified and
      scored according to the TL injury severity score (TLISS). The case histories were
      reordered and the physicians repeated the exercise 3 months later. At both
      intervals the surgeons were asked if they agreed with the final treatment
      recommendation of the TLISS algorithm. The reliability and decision validity of
      the TLISS was compared. RESULTS: Between-group interrater reliability was similar
      to within group reliabilities. Intrarater reliability was also similar between
      groups. The between speciality interrater reliability of the TLISS management
      recommendation was moderate (74% agreement, kappa=0.532). Orthopedic and
      neurosurgeons agreed with the TLISS management recommendation 91.4% and 94.4% of
      the time, respectively. CONCLUSIONS: The TLISS demonstrated good reliability in
      terms of intraobserver and interobserver agreement on the algorithmic treatment
      recommendations. The recommendation for operation seems to be consistent between
      fellowship-trained orthopedic and neurosurgical spine surgeons. This type of
      classification system may reduce the existing variability and initial management
      decision for treatment of TL injuries.

PMID- 17021411
TI  - Vertebral bone resorption after transforaminal lumbar interbody fusion with bone
      morphogenetic protein (rhBMP-2).
AB  - OBJECTIVE: Bone morphogenetic protein (rhBMP-2) has demonstrated an increased
      rate of interbody fusion when placed in the intervertebral space. Owing to this
      advantage, rhBMP-2 is being implanted with increasing frequency in the lumbar
      spine. The purpose was to quantify and describe the presence of bone resorption
      within the vertebral body after transforaminal lumbar interbody fusion with
      placement of rhBMP-2 within the disc space. METHODS: Twenty-six patients were
      selected from a clinical database. Patients included in the study had undergone a
      transforaminal lumbar interbody fusion with BMP. Interbody implants included
      allograft dowels or interbody cages augmented with autograft or allograft bone. A
      computed tomography study of the lumbar spine a minimum of 3-month
      postoperatively was another inclusion criterion. Osteolytic defects were grouped
      into 3 categories on the basis of the size and extent of involvement in the
      vertebral body. RESULTS: A total of 32 lumbar levels were reviewed. Fourteen
      males and 12 females with an average age of 46.0 years were included in the
      study. Bone resorption defects were noted in 22 of the 32 levels reviewed (69%).
      The defects were characterized as mild in 50% (11 of 22), moderate in 18% (4 of
      22), and severe in 31% (7 of 22). CONCLUSIONS: The benefit of rhBMP-2 to promote
      interbody fusion in the lumbar spine has been well documented. BMP has
      demonstrated an increased fusion rate and the ability to produce a robust fusion
      mass. rh-BMP-2's osseous remodeling potential may lead to bone resorption within
      the vertebral body.

PMID- 17021412
TI  - Wedge osteotomy for treating post-traumatic kyphosis at thoracolumbar and lumbar
      levels.
AB  - Local post-traumatic kyphosis may impair spinal sagittal balance and result in
      severe disability. The goal of this study is to evaluate posterior closing wedge
      osteotomy at the level of injury, by comparing thoracolumbar (T12-L1) and lumbar
      (L2-4) spinal levels. Thirteen consecutive patients had surgery in an average 13
      months after the initial injury. There were 8 thoracolumbar and 5 lumbar
      deformities. Nine patients already had posterior fixation. Eight patients had
      preoperative neurological deficits. Sagittal correction was assessed in terms of
      regional angulation (RA) and effective regional deformity (ERD), which was
      defined as the difference between the actual RA and the physiological RA for the
      level. The average follow up was 2.1 years. The average RA passed from 43.8
      degrees (31 to 55) to 2.2 degrees (-5 to 7) after surgery. It was 5.3 degrees (-4
      to 12), at follow-up. RA and surgical correction were not significantly different
      between thoracolumbar and lumbar groups. The average ERD was 47.2 degrees (24 to
      66) preoperatively and 8.6 degrees (-5 to 37) at follow-up. The ERD passed from
      41.8 degrees (24 to 54) to 0.5 degrees (-5 to 6) in the thoracolumbar group, and
      from 55.8 degrees (50 to 66) to 21.6 degrees (17 to 37) in the lumbar group. The
      ERD was significantly different initially (P=0.014) and after surgery (P=0.06).
      The anatomical result was complete in the thoracolumbar group, because the
      correction of the deformity at this level does not require more than correction
      of the vertebral body kyphosis. On the contrary, due to adjacent disc damage, the
      technique did not fully restore the physiological regional lordosis at lower
      levels.

PMID- 17021413
TI  - Positional MRI changes in supine versus sitting postures in patients with
      degenerative lumbar spine.
AB  - INTRODUCTION: Back pain is associated with a degree of alteration in the
      alignment and movement of the lumbar spine. The purpose of this study is to
      investigate how the degree of lumbar segmental degeneration affects sagittal
      changes in the lumbar spine as it shifts from the supine to the sitting (load
      bearing) posture. MATERIALS AND METHODS: Thirty patients with chronic low back
      pain were enrolled (14 male and 16 female patients); mean age 44.5 years. Their
      lumbar spines were initially investigated by conventional supine magnetic
      resonance imaging (MRI) followed later by positional MRI in the seated posture.
      Of the 150 discs studied, 87 were classified as healthy grade 1, 16 as grade 2,
      34 as grade 3, and 13 as grade 4. RESULTS: As the lumbar spine was loaded from
      the supine to the sitting position, the end-plate angles were decreased
      significantly as the degeneration was increased. There were also significant
      changes in the anterior and middle disc heights between the supine and the
      sitting postures irrespective of the degree of degeneration. The overall lumbar
      lordosis did not significantly change between the two postures. CONCLUSIONS: We
      have found that the changes in the segmental motion were related to the degree of
      degeneration. With positional MRI, we were able to demonstrate changes in healthy
      and degenerative discs in the weight-bearing position. More similar studies are
      needed to understand the complex kinematics of the lumbar spine.

PMID- 17021414
TI  - Measurement of lumbar lordosis: inter-rater reliability, minimum detectable
      change and longitudinal variation.
AB  - STUDY DESIGN: Repeated measures design to examine reliability and longitudinal
      variation of lumbar lordosis measurement. OBJECTIVES: To determine the interrater
      reliability, minimum detectable change (MDC) and longitudinal variation of the
      Cobb method for measuring lumbar lordosis using standardized rules. SUMMARY OF
      BACKGROUND DATA: The reliability of the 4-line Cobb method for measuring lumbar
      lordosis was not examined when standardized rules were instituted for drawing the
      lines. METHODS: A random sample of participants was selected from the Pittsburgh
      clinic of the multicenter Study of Osteoporotic Fractures for radiographic
      measurement of lumbar lordosis reliability (n=48) and stability (n=109). A
      standardized version of the 4-line Cobb method was used for all measurements of
      lordosis. The Intraclass Correlation Coefficient (ICC) was used to calculate
      interrater reliability for lordosis and to measure the stability of this measure
      over an approximate 2-year-time period. The standard error of measurement and MDC
      were calculated for lordosis measurement based on the ICC value. RESULTS: The
      interrater reliability coefficient for lumbar lordosis was in the excellent range
      (ICC=0.98; 95% CI: 0.95, 0.99). The MDC based on measurements between raters was
      3.90 degrees. The ICC value for the stability, or reliability from time 1 to time
      2, of lordosis measurement over time was 0.81 (95% CI: 0.74, 0.87). CONCLUSION:
      This study demonstrates that the 4-line Cobb method can be a highly reliable and
      precise method for measuring lumbar lordosis if standardized procedures are used.
      The Cobb method has an MDC that is appropriate for clinical use. Also, there is
      minimal longitudinal variation in lordosis measurements over a 2-year period.

PMID- 17021415
TI  - Computerized assessment of sagittal curvatures of the spine: comparison between
      Cobb and tangent circles techniques.
AB  - OBJECTIVE: The tangent circles technique has been proposed as an alternative to
      the Cobb angle technique to assess sagittal curves of the spine. However, it has
      never been compared directly to the Cobb technique. This study compares the
      reproducibility and clinical relevance of the maximum Cobb angle and tangent
      circles techniques. METHOD: Standing sagittal radiographs of the spine of 10
      adolescents with idiopathic scoliosis, 10 adolescents with spondylolisthesis, and
      10 healthy adolescents were used. Thoracic kyphosis (TK) and lumbar lordosis (LL)
      were measured by 3 observers using the maximum Cobb angle and the tangent circles
      techniques. Intra- and interobserver intraclass correlation coefficients (ICCs)
      were calculated. RESULT: Intra- and interobserver ICCs for TK were 0.88 and 0.85,
      respectively, for the maximum Cobb angle technique, and 0.94 and 0.83,
      respectively, for the tangent circles technique. Intra- and interobserver ICCs
      for LL were 0.97 and 0.77, respectively, for the maximum Cobb angle technique,
      and 0.88 and 0.94, respectively, for the tangent circles technique. The 2
      techniques were highly correlated for the measurement of the TK (r=0.93) and LL
      (r=0.88). CONCLUSION: Both techniques provide excellent intra- and interobserver
      reproducibility. Tangent circles technique may be a good alternative to the Cobb
      angle technique because it allows the evaluation of the global geometry of
      sagittal spinal curves, especially when there is limited visibility of bony
      structures on radiographs.

PMID- 17021416
TI  - Comprehensive analysis of cantilever, translational, and modular corrective
      techniques in adults with scoliosis treated with surgery to the sacropelvis.
AB  - BACKGROUND: The treatment of adults with scoliosis has been the source of debate
      over the last several decades. Pain associated with curve progression and
      decompensation is the most common presenting scenario and surgical management is
      often indicated. Correction of these deformities may involve long segment fusions
      to the sacrum and pelvis. Most authors have reported high rates of complications
      associated with this procedure. There remains little consensus with regard to the
      treatment of this challenging condition. PURPOSE: The purpose of this study was
      to evaluate the clinical and radiographic outcomes of patients treated with long
      fusions to the sacrum and pelvis using third generation instrumentation
      techniques. These included the use of cantilever, translational, and modular
      corrective techniques. METHODS: Inpatient and outpatient charts were reviewed for
      97 patients (89 women and 8 men). The average age was 55 years (27 to 78 y). The
      information obtained included patient age, sex, comorbidities, perioperative
      complications, and long-term clinical outcome. Standing radiographic coronal and
      sagittal measurements were recorded preoperatively, immediately postoperatively,
      and at the most recent follow-up visit. RESULTS: Eighty-nine patients underwent
      combined anterior and posterior surgery, whereas 8 patients were treated with
      posterior-only procedures. Two patients had fixation to the sacrum without
      extension into the ilium. Structural curves averaged 53 degrees preoperatively,
      32 degrees postoperatively, and 33 degrees at follow-up. Thoracic kyphosis
      averaged +36 degrees preoperatively, +39 degrees postoperatively, and +46 degrees
      at follow-up. Lumbar lordosis averaged -41 degrees preoperatively, -48 degrees
      postoperatively, and -48 degrees at follow-up. Coronal imbalance averaged 2.9 cm
      preoperatively, 2.4 cm postoperatively, and 2.3 cm at follow-up. Sagittal
      imbalance averaged 6.8 cm preoperatively, 2.9 cm postoperatively, and 3.6 cm at
      follow-up. Major complications included pseudarthrosis (10%), deep infection
      (13%), painful iliac fixation (20%), neurologic injury (6%), need for some form
      of revision surgery (39%), chronic severe pain (2%), pulmonary embolism (2%), and
      deep venous thrombosis (2%). There were no permanent neurologic injuries or
      deaths related to the surgery.

PMID- 17021417
TI  - Morphometric determinants of the sagittal dimensions of the cervical spinal canal
      in achondroplasia: an analysis of the reliability of the Torg ratio.
AB  - This study was undertaken to evaluate the accuracy of the Torg ratio for
      predicting the spinal canal stenosis in achondroplasia, by trying to establish
      its correlation with the corresponding effective sagittal canal diameter (ESCD)
      and dural sac ratio (DSR) on the MRI of the cervical spine. Lateral radiographs
      and the sagittal and axial MRI study of the cervical spine from C3 to C7 level
      were carried out in 18 asymptomatic achondroplasia subjects. A total of 90 levels
      were evaluated on the lateral radiographs and on the mid sagittal T2 MR images.
      On statistic analysis, the highest correlation coefficient for the Torg ratio
      compared with the ESCD was 0.74 at C6 level and the least was 0.45 at the C5
      level. The highest correlation coefficient between the Torg ratio and the DSR was
      0.79 at C3 level and the least was 0.42 at the C5 level. The highest coefficient
      of determination for the ESCD was 54% at C6 which translates into a poor
      correlation. The highest coefficient of determination for the DSR was 62 at C3
      level, indicating a variable correlation. These results clearly show that the
      Torg ratio is of limited value in the assessment of the true sagittal spinal
      canal diameter in achondroplasia and its reliability as an indicator of severe
      cervical canal stenosis is questionable.

PMID- 17021418
TI  - Confusion regarding mechanisms of injury in the setting of thoracolumbar spinal
      trauma: a survey of The Spine Trauma Study Group (STSG).
AB  - The Spine Trauma Study Group (STSG) developed the thoracolumbar injury severity
      score to direct the management of thoracolumbar spine injuries. The original
      system is based on 3 variables: the mechanism of injury as determined by imaging
      studies, the integrity of the posterior ligamentous complex, and the neurologic
      status of the patient. Considerable controversy exists among treating physicians
      in classifying injury mechanisms. The purpose of this study was to survey the
      STSG on case examples related to the mechanism of thoracolumbar injury. A 2
      question survey regarding thoracolumbar injury mechanisms and scoring was
      distributed to members of the STSG. A total of 27 STSG members completed surveys
      on defining and scoring thoracolumbar injury mechanisms. Data from these
      completed surveys were analyzed using a 2-tailed Fisher exact test on a chi2
      contingency table. Sixty-seven percent of physicians preferred a definition
      incorporating posterior ligamentous complex disruption without posterior
      vertebral body retropulsion over the location of the axis of rotation in
      differentiating flexion-distraction from advanced stage flexion-compression
      injuries, representing a statistically significant difference (P=0.0285). There
      was no statistical consensus on the scoring emphasizing a primary and secondary
      mechanism of injury in complex injury patterns. Despite the statistical consensus
      to 1 survey question, there seems to be no dominating opinion on distinguishing
      thoracolumbar injury mechanisms. Perhaps identifying objective findings on
      imaging studies and clinical examination in place of guessing injury mechanisms
      may allow for a more reliable and valid thoracolumbar injury classification
      system.

PMID- 17021419
TI  - Cervical meningocele causing symptoms in adulthood: case report and review of the
      literature.
AB  - Simple meningoceles are infrequent forms of dysraphism and are often benign.
      These lesions are usually associated with other congenital spinal anomalies, and
      are typically diagnosed in childhood. Most become symptomatic in childhood
      because of progressive spinal cord or nerve root tethering. This article
      describes the case of a 47-year-old man who presented with a sac in his posterior
      cervical region that had been leaking colorless fluid for 3 months. He was also
      having difficulty walking and complained of stiffness in his lower extremities.
      Cervical magnetic resonance imaging revealed a cystic mass in the region of the
      C4 to C5 laminae. Partial laminectomies were performed (lower portion C4 lamina,
      upper portion C5 lamina), the sac was totally excised, and tissue tethering the
      spinal cord were cut. There was no recurrence of symptoms in 12 months of follow
      up. Although in cases where a cervical meningocele-myelomeningocele is detected
      at any time, early treatment is essential to eliminate the high risk of future
      neurological impairment. This is the first report of an untreated cervical
      meningocele manifesting symptoms in adulthood.

PMID- 17021420
TI  - A large adolescent idiopathic scoliosis curve in a skeletally immature patient:
      is early surgery the correct approach? Overview of available evidence.
AB  - The goal of this study was to determine whether the available studies provide
      enough evidence that, in a borderline case of adolescent idiopathic scoliosis
      with a large (35 to 50 degrees) curve in a skeletally immature patient (Risser 0
      to 2) with significant growth potential left, a conservative line of management
      in the form of bracing can be considered, rather than to rush into a potentially
      unnecessary major spinal surgery. We reviewed the literature spanning the last 20
      years for the results of bracing in this specific group of patients. From the 9
      studies selected, a group-specific data extraction was carried out. Three hundred
      and five patients with a 36 to 50 degrees scoliosis curve and Risser stages 0 to
      2 were treated by bracing and the treatment was termed successful in 160
      patients. Thus, more than half (52.5%) of the patients were successfully managed
      with a brace and were spared surgery. The current trend for management of these
      curves is early surgical intervention, the rationale being the ineffectiveness of
      bracing in preventing the progression of such a large curve and the difficulty in
      obtaining satisfactory correction by postponing surgery to a later date. On the
      basis of our results, we propose a conservative line of management for these
      curves, in contrast with current views, rather than to rush into a major spine
      surgery, expecting a favorable outcome with a well-supervised bracing program. If
      the curve progresses, surgery can always be considered later, keeping in mind the
      excellent correction obtained with the pedicle screw systems even for large
      curves of 70 to 100 degrees.

PMID- 17021421
TI  - Sentinel lymph node biopsy in differentiated thyroid cancer: standard of care or
      experimental tool?

PMID- 17021422
TI  - Efficacy of milk versus water to reduce interfering infra-cardiac activity in
      99mTc-sestamibi myocardial perfusion scintigraphy.
AB  - OBJECTIVE: Interference from infra-cardiac radionuclide activity prevents
      accurate interpretation of true myocardial perfusion. The study aim was to
      compare the efficacy of milk versus water in reducing infra-cardiac activity in
      myocardial perfusion scintigraphy. METHODS: We prospectively randomized 198
      patients undergoing stress-rest (99m)Tc-sestamibi SPECT with exercise or
      pharmacological stress to drink 300 ml of water or milk prior to imaging. A semi
      quantitative grading of the relative intensity of infra-cardiac activity compared
      to the myocardial activity and a qualitative assessment of the effect on the
      overall interpretation was performed. RESULTS: For stress images, there was no
      infra-cardiac activity in 37.9%, less intense infra-cardiac activity in 40.8%,
      equal in 11.7% and greater than infra-cardiac activity in 9.7% with milk,
      compared with 20.0%, 49.5%, 20.0% and 10.5%, respectively, with water (P=0.038).
      For rest images, there was also less intense infra-cardiac activity with milk
      compared to water (P=0.014). However, no change in subsequent image
      interpretation was seen. CONCLUSION: Administration of milk resulted in a
      significant decrease in the intensity of infra-cardiac activity compared to
      water. However, this did not translate into an improvement in image
      interpretation.

PMID- 17021423
TI  - The value of registration correction in the attenuation correction of myocardial
      SPECT studies using low resolution computed tomography images.
AB  - BACKGROUND: Artifacts caused by tissue attenuation create problems in the
      interpretation of myocardial perfusion studies. In a previous study we evaluated
      attenuation correction using 'Hawkeye' and noted that the incidence of
      anterior/apical defects increased after attenuation correction. This increased
      incidence appeared to be associated with mis-registration between emission and
      transmission images. The main aim of this study was to determine whether
      correction of mis-registration between emission and transmission scans reduced
      the incidence of these anterior/apical defects. METHODS: Ninety-four patients (64
      men, 30 women) underwent stress/rest myocardial perfusion imaging using (99m)Tc
      tetrofosmin (188 studies). Bull's-eye perfusion plots were created using
      proprietary software (QPS). RESULTS: The marked reduction in defect size,
      particularly obvious in male patients, in the inferior wall after attenuation
      correction was not significantly changed by the addition of registration
      correction. In the anterior and apical walls attenuation correction produced a
      confusing pattern particularly in females with an overall tendency to increase
      the defect size. After registration correction fewer anterior/apical defects were
      created. CONCLUSION: Attenuation correction using 'Hawkeye' reduces the incidence
      of inferior myocardial perfusion defects but can create anterior and/or apical
      artifacts. It is essential to evaluate registration carefully in three dimensions
      before reporting the images. Correction of mis-registration reduces the incidence
      of anterior/apical defects and can restore the appearance of the anterior/apical
      area to pre-correction levels.

PMID- 17021424
TI  - X-ray-based attenuation correction of myocardial perfusion scans: practical
      feasibility and diagnostic impact.
AB  - OBJECTIVES: This study describes the practical implementation of X-ray-based
      attenuation correction (AC) of myocardial perfusion scans in a large teaching
      hospital, characterizes the impact of AC on the diagnostic confidence of the
      interpreter and tries to predict which patients are likely to benefit from the
      technique. METHODS: One hundred and seven consecutive patients underwent a 2 day
      (99m)Tc-tetrofosmin protocol with adenosine stress using GE Millennium VG with AC
      and ECG-gated acquisition (ECG-g). The diagnostic impact of AC/ECG-g was judged
      by a panel of three observers. RESULTS: AC was not achieved in 46 patients.
      Individual observers rated AC 'essential' in 37 scans and 'helpful' in 68 scans.
      For ECG-g, this applied to 12 and 78 scans, respectively. The rating for AC was
      better than that for ECG-g in 57 scans, and vice versa in 31 scans. Equal ratings
      were recorded in 41 scans, and neither technique was needed in 54 scans.
      Diagnostic interpretation of abnormal scans was significantly more likely to
      benefit from either AC or ECG-g than interpretation of normal scans. Patients in
      whom AC was considered useful had a significantly higher body mass and chest
      circumference, but the overlap was large. CONCLUSIONS: In practice, AC was not
      feasible in a significant proportion of our patients. AC received better ratings
      from observers more often than ECG-g. Interpreter confidence with AC was
      significantly greater in scans with perfusion defects than in normal scans. Body
      mass and chest circumference cannot be used to predict which patients will
      benefit from AC.

PMID- 17021425
TI  - Acceleration of hepatobiliary excretion by lemon juice on 99mTc-tetrofosmin
      cardiac SPECT.
AB  - BACKGROUND: We sought to determine whether drinking lemon juice reduces extra
      cardiac activity and improves image quality on (99m)Tc-tetrafosmin myocardial
      single photon emission computed tomography (SPECT). METHODS: Eighty male patients
      were enrolled in this study and divided into four groups with 20 patients in each
      group. Each patient received 259-333 MBq tetrofosmin. Ten minutes after injection
      no action was taken for group 1 (G1), patients in group 2 (G2) each drank 250 ml
      of water, patients in group 3 (G3) each drank 250 ml of whole milk, and patients
      in group 4 (G4) each drank 250 ml diluted lemon juice. Myocardial perfusion
      imaging without attenuation correction was performed after a 1 day rest-stress
      protocol. Both rest and stress images were aligned at corresponding slices for
      comparison. Interfering activity was determined visually on reconstructed images,
      and the heart-to-liver (H/L) ratios were calculated with planar images at 25-30
      min and at 45-50 min. RESULTS: Interfering activity was seen in 80% of G1, 70% of
      G2, 60% of G3, and 35% of G4 (G4 vs. G1, P=0.006) on rest images, and in 70% of
      G1, 60% of G2, 55% of G3, and 30% of G4 (G4 vs. G1, P=0.014) on stress images at
      25-30 min. It was also observed in 60% of G1, 50% of G2, 45% of G3, and 15% of G4
      (G4 vs. G1, P=0.006) on rest images, and in 50% of G1, 45% of G2, 40% of G3, and
      10% of G4 (G4 vs. G1, P=0.011) on stress images at 45-50 min. The mean H/L ratios
      of rest images were 0.47+/-0.13 for G1, 0.71+/-0.17 for G2, 0.65+/-0.12 for G3,
      and 0.93+/-0.23 for G4 at 25-30 min, and 0.63+/-0.14 for G1, 0.73+/-0.14 for G2,
      0.85+/-0.25 for G3, and 1.15+/-0.25 for G4 at 45-50 min. On stress images, they
      were 0.49+/-0.11 for G1, 0.74+/-0.16 for G2, 0.69+/-0.11 for G3, and 0.98+/-0.22
      for G4 at 25-30 min, and 0.66+/-0.15 for G1, 0.77+/-0.11 for G2, 0.89+/-0.26 for
      G3, and 1.21+/-0.19 for G4 at 45-50 min. CONCLUSION: Drinking 250 ml of diluted
      lemon juice accelerates the transit of tetrofosmin through the liver parenchyma
      and improves image quality on (99m)Tc-tetrafosmin myocardial SPECT.

PMID- 17021426
TI  - Clinical value of planar and tomographic dual-isotope scintigraphy using 99mTc
      methylene diphosphonate and 131I in patients with thyroid cancer.
AB  - PURPOSE: (131)I whole-body scintigraphy is a highly sensitive method for the
      detection of differentiated thyroid tumours and metastases. However, a lack of
      anatomical landmarks and the physiological excretion of the tracer complicates
      the evaluation of the images. Therefore, we determined whether additional bone
      scintigraphy in combination with (131)I scintigraphy, simultaneously acquired via
      planar and tomographic techniques, positively contributes to the treatment plan
      in patients with non-conclusive (131)I images. METHODS: Twenty-one patients with
      differentiated thyroid cancer and known metastases or unclear findings in the
      (131)I whole-body scan underwent dual-isotope scintigraphy (DIS) within 2-7 days
      after application of 5000-8000 MBq (131)I. Dual-energy planar and tomographic
      data were acquired simultaneously and the results compared with other imaging
      modalities. RESULTS: In 48% of the cases (10 of 21), DIS supplied important
      additional information that either altered the treatment plan or staging of the
      patients. In 28% (six of 21), DIS provided new information that was not known
      before, but did not change the staging of the patients. In five cases (24%), DIS
      did not add any new data regarding the extent of the disease. CONCLUSIONS: The
      simultaneous acquisition of (131)I and (99m)Tc-methylene diphosphonate provides
      clear landmarks and facilitates the localization of functioning metastases from
      differentiated thyroid cancer as well as improves the fusion with morphological
      images. It can be performed easily and also transferred to other isotope
      combinations.

PMID- 17021427
TI  - Clinical importance of anti-thyroglobulin auto-antibodies in patients with
      differentiated thyroid carcinoma: comparison with 99mTc-MIBI scans.
AB  - AIMS: (1) To investigate whether elevated serum anti-thyroglobulin antibody (ATG)
      reflects the recurrence of cancer in patients with differentiated thyroid
      carcinoma (DTC) in whom thyroglobulin was undetectable after radioiodine
      ablation. (2) To assess the sensitivity of disease detection for (99m)Tc-MIBI
      whole-body scans (WBSs) in these patients and investigate the correlation between
      MIBI WBS results and high serum ATG levels. MATERIALS AND METHODS: In this
      retrospective study, we evaluated 14 patients (13 women and 1 man; mean age 44 +/
      19 years) with DTC who underwent total or near-total thyroidectomy followed by
      an ablative dose of I at various time intervals. According to histopathological
      findings, 10 patients (71.4%) who were diagnosed as having papillary carcinoma
      and four patients (28.6%) as having follicular cell carcinoma, had high serum ATG
      concentrations (> 40 IU x ml(-1); range, 62-2000 IU x ml(-1)), but low serum
      thyroglobulin concentrations (< 1.6 ng x ml). Post-therapeutic and diagnostic
      (131)I WBSs and (99m)Tc-MIBI WBSs were performed. Scans were visually evaluated
      for detecting recurrence. If necessary, bone scans, chest X-rays, computerized
      tomography, ultrasonography and histopathological evaluation were performed.
      RESULTS: Recurrent and/or persistent disease was found in 12 of the patients.
      This was confirmed pathologically in four patients and by using other imaging
      methods in eight (bone scans, computerized tomography, ultrasonography). The
      sensitivity and specificity of disease detection for MIBI WBSs was 66.7% and
      100%, respectively. For (131)I WBSs, the sensitivity of disease detection was
      55.6%. Among these 12 patients, 10 responded to treatment (three underwent
      surgery, seven received radioiodine therapy, and two had surgery + radioiodine
      therapy). ATG levels decreased in eight of the 10 patients, but remained
      persistently elevated in two despite treatment. CONCLUSIONS: (1) Persistently
      elevated ATG levels appear to serve as a useful marker for recurrent or
      persistent DTC in patients with undetectable serum tyroglobulin levels. Thus, the
      routine measurement of ATG antibody in such patients is of great value. (2) In
      these patients, (99m)Tc-MIBI has a relatively high sensitivity in the diagnosis
      of a recurrence of thyroid cancer or metastases. So, in patients with elevated
      ATG but undetectable serum thyroglobulin levels, (99m)Tc-MIBI can be used to
      determine whether there is a recurrence of DTC or metastases.

PMID- 17021428
TI  - A report on the incidence of intestinal 99mTc-methylene diphosphonate uptake of
      bone scans and a review of the literature.
AB  - BACKGROUND: In addition to well-known specific conditions for soft-tissue uptake
      of bone-seeking radiotracers, there is a limited number of reports on intestinal
      uptake of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) on bone scans. AIM: To
      describe the incidence of intestinal accumulation of (99m)Tc-MDP on bone scans in
      adult patients, define the patterns of this unusual finding and review the
      literature on its causes. METHODS: Two thousand, one hundred and forty-four
      consecutive patients have been evaluated for intestinal (99m)Tc-MDP uptake on
      bone scans. Intestinal uptake was observed visually 3-4 h after the
      administration of the radiopharmaceutical. A whole-body bone scan and various
      spot views of the abdomino-pelvic region were obtained with a dual-headed gamma
      camera to evaluate the intestinal uptake. Delayed scans were also obtained as
      well as co-relative imaging and/or colonoscopic studies in some of intestinal
      uptake patients. Six patients had delayed scans of the abdomino-pelvic region.
      Fourteen patients had comparable scans either a year before or a year later. The
      positive intestinal uptake scans were further grouped according to the
      localization and intensity (mild uptake: lower than iliac bone; moderate uptake:
      equal to iliac bone; significant uptake: higher than iliac bone). RESULTS: Twenty
      two (17 female, five male) patients out of 2144 with a mean age of 57 years
      showed intestinal (99m)Tc-MDP uptake. The localization was mainly (20/22) in the
      right abdomino-pelvic region projecting on and in the configuration of ascending
      colon while one patient showed intestinal uptake all over the abdomen and one
      displayed diffuse intestinal radioactivity in his right hemithorax. The majority
      of the cases showed moderate to intense intestinal uptake (18/22). Six patients
      showed a decrease, disappearance or alteration in the intestinal uptake on the
      delayed images. Re-evaluation bone scans in five patients 1 year later showed no
      intestinal uptake this time. Among nine patients with prior bone scans 1 year
      before, intestinal uptake was negative in seven at that time. No significant
      pathology was obtained on the correlative images. CONCLUSION: (99m)Tc-MDP uptake
      can be observed in the intestines in 1% of bone scans with a prominent
      localization in the ascending colon and rarely all over the intestines or in
      thorax due to Chilaiditi's syndrome, as well. The mechanism of intestinal uptake
      is still unclear in some of the patients. Delayed imaging, additional spot views
      and SPECT studies help in the differentiation of this finding from possible
      misinterpretation. Intestinal (99m)Tc-MDP uptake on bone scan could be an
      intermittent process and should be included among other well-known reasons of
      soft-tissue uptake.

PMID- 17021429
TI  - Usefulness of 99mTc-Technegas and 133Xe dynamic SPECT in ventilatory impairment.
AB  - AIM: To assess the usefulness of SPECT images using (99m)Tc-Technegas (Technegas)
      and (133)Xe dynamic single photon emission computed tomography (SPECT) (Xe gas)
      and high-resolution computed tomography (HRCT), as compared with pathological
      assessment in the detection of small-airway disease including pulmonary
      emphysema. METHODS: Seventeen patients with lung cancer were studied. All
      patients who had undergone both Technegas and Xe gas and CT prior to surgery were
      examined. SPECT and HRCT results were compared with the results of pathological
      findings. Histopathological analysis was performed in an area distant from cancer
      in lobectomy specimens obtained at surgery. Pathological analysis was performed
      in relation to bronchitis, bronchiolitis, fibrosis of the alveoli and disruption
      in walls of the alveoli. RESULTS: Pathological abnormality (mild-to-moderate
      abnormal change) was seen in all 17 cases. Three patients showed low attenuation
      areas on CT, and abnormal patterns in SPECT images. In 11 of 14 patients who
      showed normal findings on CT, SPECT imaging depicted abnormal findings. The
      remaining three patients had no abnormal findings on CT and both SPECT imaging.
      CONCLUSION: Technegas and (133)Xe SPECT imaging is useful for evaluating small
      airway disease including pulmonary emphysema. Furthermore, SPECT imaging is more
      useful than morphological HRCT imaging in the evaluation of small-airway disease
      including pulmonary emphysema.

PMID- 17021430
TI  - Pre-surgical identification of epileptogenic areas in temporal lobe epilepsy by
      123I-iomazenil SPECT: a comparison with IMP SPECT and FDG PET.
AB  - OBJECTIVES: The aim of this study was to evaluate the usefulness of (123)I
      iomazenil (IMZ) single photon emission computed tomography (SPECT) for the pre
      surgical identification of epileptogenic areas in patients with temporal lobe
      epilepsy and to compare the results with those of (123)I-IMP SPECT and
      (18)Fluorodeoxyglucose positron emission tomography (FDG PET). METHODS: We
      examined seven patients with medically refractory temporal lobe epilepsy (five
      men and two women; mean age, 28 years) with no remarkable findings on magnetic
      resonance imaging. Before surgery, IMZ SPECT, IMP SPECT and FDG PET were all
      performed in the interictal state. Then, visual assessment and region-of-interest
      (ROI) analysis were performed on each image. Final definitions of the
      epileptogenic areas were made by electrocorticography and histopathology.
      RESULTS: By IMZ SPECT, a decreased IMZ uptake in the ipsilateral temporal lobe
      was found in all patients, while a similar decrease in the contralateral temporal
      lobe was also found in one patient. In comparison to IMP SPECT, the extent of the
      abnormal area on IMZ SPECT was equal to that on IMP SPECT in one patient while it
      was more restricted to the epileptogenic area in five patients. In comparison to
      FDG PET, the extent of the abnormal area on IMZ SPECT was equal to that on FDG
      PET in three patients while it was more restricted in the epileptogenic area in
      four patients. In ROI analysis, decreases of IMZ, IMP and FDG uptake were
      observed in the epileptogenic area, although they were not statistically
      significant. CONCLUSIONS: IMZ SPECT was considered to be useful for pre-surgical
      determination of the epileptogenic areas in temporal lobe epilepsy with no
      remarkable MRI findings, and it was also found to be superior to IMP SPECT and
      FDG PET for this purpose.

PMID- 17021431
TI  - Characterization of septal penetration in 511 keV SPECT.
AB  - BACKGROUND: Single photon emission computed tomography (SPECT) with 511 keV
      photons is a challenging modality and collimators for this purpose require trade
      offs among resolution, sensitivity and septal penetration. While PET is the
      modality of choice for imaging at 511 keV, there are some procedures, e.g., dual
      isotope imaging, in which 511 keV SPECT has a role. AIM: To measure the imaging
      properties of a VPC-93 SPECT collimator designed for imaging at 511 keV and to
      isolate the effects of septal penetration. METHODS: NaI gamma camera projection
      images of (18)F (511 keV) and (99m)Tc (140 keV) point sources were measured and
      the corresponding modulation transfer functions calculated. The projection images
      were reconstructed via filtered back-projection to obtain the tomographic three
      dimensional (3-D) point spread function. Differences between the 511 and 140 keV
      results were attributed mainly to septal penetration. Contrast measurements were
      made separately using (18)F and (99m)Tc of a 20 cm phantom containing hot spheres
      and a warm background. Both isotopes were also used in imaging studies of a 3-D
      Hoffman brain phantom. RESULTS: Reconstructed 511 keV point source images were
      spatially extended with more than half of the total reconstructed counts
      appearing away from the point source region. The number of false counts contained
      in the image as a function of distance from the true source location remains
      approximately constant for large distances out to at least 14 cm. Septal
      penetration results in a rapid roll-off with spatial frequency of collimator
      response. The response of the collimator to 511 keV photons falls to half of its
      0-frequency response at 0.03 cm(-1). For 140 keV photons this value is 0.20 cm(
      1). A result is reduced image contrast as measured in the phantom sphere studies.
      Septal penetration causes image degradation through large-scale blurring. Image
      noise characteristics are modified and correlations are extended into many
      transaxial planes. CONCLUSIONS: Both 2-D and 3-D point spread functions for 511
      and 140 keV photons using the VPC-93 collimator have been measured. Septal
      penetration unfavourably affects image resolution and changes image noise
      characteristics. Without compensation, the effects of septal penetration are
      readily apparent in images of real objects.

PMID- 17021432
TI  - Scintimammographic detection of usual ductal breast hyperplasia with increased
      proliferation rate at risk for malignancy.
AB  - OBJECTIVES: To estimate whether breast uptake of (99m)Tc-(V)DMSA and (99m)Tc
      sestamibi in usual ductal epithelial breast hyperplasia (UDH) and apocrine
      metaplasia is related to cell proliferation rate (Ki-67) and oestrogen receptor
      (ER) expression, both of which are associated with the potential risk of evolving
      to malignancy. METHODS: Among patients referred for suspicious breast findings on
      palpation and/or mammography and evaluated preoperatively with both
      radiopharmaceuticals, we retrospectively studied 17 (10 with UDH: group I; and
      seven with apocrine metaplasia: group II). Lesion-to-background (L/B) ratios in
      early and late acquisitions were calculated for both radiotracers in both groups,
      as well as their retention ratios. Ki-67 and oestrogen receptor expression were
      determined immunohistochemically. The late L/B ratios between the two tracers
      were compared, as were the late ratios for each tracer between Ki-67 < or = 3%
      and > 3%, and between ER < or = 15% and > 15%. Linear regression analysis was
      also performed between L/B and retention ratios and Ki-67 expression. RESULTS:
      There was a significant increase of the (99m)Tc-(V)DMSA L/B ratio in late images
      as compared to the early images in group I (P<0.05), while in group II it was not
      significantly increased (P=0.084). (99m)Tc-sestamibi ratios did not demonstrate
      variability over time in either group (P=0.156 and 0.274, respectively).
      Significant coefficient correlation was found between the (99m)Tc-(V)DMSA
      L/B(late) ratios and retention ratios and Ki-67 levels only for group I (r=0.889,
      P<0.001 and r=0.802, P<0.01, respectively). The (99m)Tc-(V)DMSA L/B(late) ratios
      in group I were significantly higher when Ki-67 > 3% than when Ki-67 < or = 3%
      (P=0.016) but did not differ considerably between ER > 15% and < or = 15%
      (P=0.732). CONCLUSION: (99m)Tc-(V)DMSA uptake in UDH correlates with Ki-67
      expression. This could prove useful in identifying women with benign but high
      risk breast pathologies who might benefit from chemoprophylaxis.

PMID- 17021433
TI  - Incidence and radio-uptake patterns of femoral head avascular osteonecrosis at 1
      year after renal transplantation: a prospective study with planar bone
      scintigraphy.
AB  - OBJECTIVES: We prospectively investigated the incidence of femoral head avascular
      osteonecrosis (AVN) and radio-uptake patterns of femoral heads on bone
      scintigraphy at 1 year after renal transplantation. METHODS: A total of 237
      subjects (473 femoral heads) were included. A bone scintigraphy was performed at
      12 +/- 1.1 months after renal transplantation, and 17 hips were painful at the
      time of bone scintigraphy. We graded the radioactivity in each femoral head as
      normal (grade 0), mildly increased (grade I), and definitely increased (grade
      II). Typical photon defects in the upper lateral femoral heads were evaluated
      separately. AVN was confirmed with clinical follow-up of more than 1 year and MRI
      and/or plain radiography findings. RESULTS: Femoral head AVN was detected in 15
      of the 237 patients and 23 of the 473 femoral heads. When grade I and II
      activities were used as positive criteria, bone scintigraphy had a sensitivity of
      91.3% (100% with pain) and specificity of 74.0% (100% with pain) for AVN
      diagnosis. When only grade II activity was considered positive, the rates were
      56.5% (80.0% with pain) and 99.5% (100% with pain), respectively. The presence of
      a typical photon defect had a low sensitivity of 47.8%, although the specificity
      was high (99.1%). CONCLUSIONS: The incidence of femoral head AVN was low among a
      prospective cohort of renal transplantation recipients at the time of 1 year
      after engraftment. Planar bone scintigraphy is sufficient to diagnose AVN in
      symptomatic patients at risk for femoral head AVN using grade I and II activities
      as positive criteria.

PMID- 17021435
TI  - Research in cardiovascular anesthesia: preparing the subspecialty for a bright
      future.

PMID- 17021436
TI  - Angiogenesis therapies for cardiovascular disease.
AB  - PURPOSE OF REVIEW: The purpose was to summarize the findings of the proangiogenic
      clinical trials using protein and gene therapy, with analysis of the problems and
      an interpretation of the results. RECENT FINDINGS: Recent findings include
      several new large clinical trials, using both gene and protein therapies. There
      has been development of new basic science concepts, especially with regard to
      endothelial activation and stabilization of newly formed microvessels. This
      review provides a critical analysis of the most recent clinical trials, both in
      efforts to understand the pitfalls of earlier clinical trials, and also to focus
      on requirements for future studies. SUMMARY: This article reviews many of the
      clinical trials utilizing proangiogenic therapy, assesses the pitfalls seen
      within the current trials, and discusses the conclusions drawn and the future of
      angiogenesis therapy.

PMID- 17021437
TI  - Intraoperative assessment of diastolic function: utility of echocardiography.
AB  - PURPOSE OF REVIEW: This review discusses the current and future applications of
      different echocardiographic modalities in evaluating diastolic function
      intraoperatively. RECENT FINDINGS: Normal diastolic function is required for
      optimal cardiac performance. There is sufficient evidence to support the
      significant prevalence of preoperative diastolic dysfunction and its incidence
      following cardiac surgery, however controversy still exists regarding the impact
      of diastolic dysfunction on adverse outcomes. Echocardiography provides a
      relatively safe, practical and noninvasive means to evaluate perioperative
      diastolic function, however conventional measures may be limited by the impact of
      changes in heart rate, rhythm and loading conditions. Newer echocardiographic
      modalities are reportedly less sensitive to acute changes in loading conditions,
      and may therefore complement the use of conventional echocardiographic techniques
      in the perioperative period. SUMMARY: The availability of effective technology
      for diagnosing the presence and progression of perioperative diastolic function
      should assist in the identification of high-risk cardiac surgical patients who
      may benefit from appropriate triaging and therapeutic intervention.

PMID- 17021438
TI  - Oxygen therapeutics (blood substitutes) in cardiac surgery.
AB  - PURPOSE OF REVIEW: Discuss and summarize recent published literature related to
      the use of 'blood substitutes' in cardiac surgery patients. RECENT FINDINGS:
      Concerns about safety, inventory and the cost of allogenic blood transfusion have
      led to the continued interest to find an ideal oxygen carrier 'blood substitute'
      for cardiac surgery patients. Two classes of oxygen therapeutics 'blood
      substitutes' are being investigated: (1) perfluorocarbons are synthetic
      fluorinated hydrocarbons which increase dissolved oxygen in the fluid phase and
      (2) hemoglobin-based oxygen carriers, modified to improve oxygen dissociation
      properties and side effects profiles of free hemoglobin. Hemoglobin-based oxygen
      carriers from bovine and human sources are being tested in phase III trials in
      cardiac surgery patients as well as a variety of other surgical and nonsurgical
      settings. Recombinant human hemoglobin and encapsulated hemoglobins of any source
      are emerging. Safety and cost effectiveness are being evaluated for their use as
      an alternative to blood transfusion or along with other strategies of blood
      conservation in cardiac surgery. SUMMARY: One hemoglobin-based oxygen carrier
      (Hemopure) has been approved for use in humans in South Africa as well as another
      hemoglobin-based oxygen carrier (Gelenpol) and a perfluorocarbon (Perfluoron) in
      Russia. Phase III trials in Europe and North America will be concluded very soon.
      We anticipate seeing one or two products approved in North America and Europe by
      the year 2003/2004.

PMID- 17021439
TI  - Advances in cardiopulmonary bypass circuitry.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present developments in
      cardiopulmonary bypass circuitry, and to give the authors' opinions on the causes
      of the potentially harmful processes that are initiated by cardiopulmonary
      bypass, and how they may be attenuated. RECENT FINDINGS: Much of the recently
      published work investigates the effect of various forms of biocompatible
      circuitry, either heparin bonded, or polymer coated. The increasing number of
      patients having off-pump coronary surgery allows comparison of such patients with
      those that have had surgery using the various forms of cardiopulmonary bypass
      circuitry. SUMMARY: Recent developments of biocompatible circuits are promising
      in terms of their potential for reducing the perioperative inflammatory response.
      The use of such circuitry, however, is likely to be of benefit only when included
      as part of an overall strategy to control triggers of the inflammatory response
      during and after cardiac surgery, particularly in the high-risk patient.

PMID- 17021440
TI  - Ventricular assist devices.
AB  - PURPOSE OF REVIEW: Recent advances in technology as well as new indications for
      implantation have appeared in the field of ventricular assist devices. Progress
      has also been made in the understanding of the underlying mechanisms of
      myocardial recovery after ventricular assist device support. RECENT FINDINGS:
      Technological progress includes the development of fully implantable pulsatile
      and continuous flow pumps, either axial flow or centrifugal, for left ventricular
      and total heart assistance. Among the new indications for ventricular assist
      device support, the most important is the use of the device as permanent
      treatment for end-stage cardiac failure patients. Increased knowledge has been
      acquired regarding the effects of mechanical assistance and of unloading of the
      heart on haemodynamics, as well as on the cellular, molecular and
      electrophysiological characteristics of the failing heart. All these findings
      suggest that depressed myocardial function can sometimes recover with ventricular
      assist device therapy. Ventricular assist device support, however, still carries
      a high rate of complications: the device itself can fail, bleeding and
      thromboembolism are common, immunity is disturbed and the incidence of infection
      remains high. SUMMARY: In patients with end-stage heart failure, ventricular
      assist devices can be used as a bridge to transplantation or to recovery, but
      they are now also considered as a long-term myocardial replacement therapy. Which
      device is the most appropriate for each indication, however, remains to be
      defined. Even if the underlying mechanisms of myocardial recovery are
      progressively clarified, the use of ventricular assist devices as a bridge to
      recovery still has limited clinical success. Clinical trials with the fully
      implantable devices are in their early stages, but these pumps appear promising
      in terms of efficacy, reliability and complication rate, as well as being easy to
      implant. Because more patients will benefit from ventricular assist device
      placement in the future, anaesthesiologists must be prepared to manage patients
      undergoing ventricular assist device placement or presenting for noncardiac
      surgery while under ventricular assist device support.

PMID- 17021441
TI  - Renal dysfunction after vascular surgery.
AB  - PURPOSE OF REVIEW: The purpose of this review is to focus on the static incidence
      of renal dysfunction, the lack of evidence of benefit of traditional
      renoprotective strategies, and newer techniques that may provide an insight into
      the mechanisms of acute perioperative renal injury associated with vascular
      surgery. RECENT FINDINGS: Recent studies that have investigated the long-term
      results of aortic surgery still report a significant incidence of postoperative
      renal dysfunction. This finding remains consistent in several reports. However,
      less invasive techniques such as endovascular repair seem to be associated with
      reduced inflammation and postoperative renal dysfunction. The possible
      association between genetic heterogeneity and renal dysfunction in vascular
      surgical patients is an exciting new area of research. SUMMARY: Renal dysfunction
      after major vascular surgery remains a significant problem. New insights into the
      mechanisms of acute renal injury and less invasive techniques of vascular repair
      may help reduce the incidence of renal dysfunction in this patient population.
      The lack of a truly 'renoprotective' agent has hampered our efforts in preventing
      this major complication of vascular surgery.

PMID- 17021442
TI  - Surgical treatment of end-stage emphysema: current status?

PMID- 17021443
TI  - Modulating the pulmonary circulation: an update.
AB  - PURPOSE OF REVIEW: Disorders of the pulmonary circulation might develop as a
      primary disease process of the pulmonary vascular bed or, more often, as the
      acute or chronic consequence of pulmonary or cardiac pathologies. For the
      anaesthesiologist and intensivist it is particularly interesting to gain insight
      into the regulation of the pulmonary circulation since pulmonary hypertension and
      concomitant right heart failure contribute to high perioperative mortality rates
      in patients at risk, especially after cardiac surgery. Therefore, modulation of
      the pulmonary circulation may be a life-saving therapy in patients suffering from
      acute or chronic pulmonary circulatory disorders. Furthermore, routinely
      performed intra-operative interventions such as the use of volatile anaesthetics
      or cardiopulmonary bypass systems may have relevant side effects on the pulmonary
      circulation. RECENT FINDINGS: This review focuses on new insights into the
      modulation of pulmonary circulation during general anaesthesia with volatile
      anaesthetics and anaesthesiological management during cardiopulmonary surgery.
      Recent publications in the field of cardiopulmonary bypass surgery, one-lung
      ventilation and heart and lung transplantation are discussed. Furthermore, the
      role of conventional and experimental therapeutic strategies to modulate
      pulmonary circulation in intensive care medicine is reviewed. SUMMARY: Despite
      the performance of a large number of clinical and experimental studies, the
      pathophysiology of pulmonary circulatory disorders is not completely understood.
      Therefore, any new therapy has to be carefully evaluated as a therapeutic option.
      Several formerly experimental therapeutic interventions such as inhaled
      vasodilators, however, appear to have found their way into clinical practice for
      selected indications.

PMID- 17021444
TI  - Anesthesia for pulmonary stent insertion.
AB  - PURPOSE OF REVIEW: To familiarize anesthesiologists with recent advances in
      endoscopic pulmonary stenting. These interventions have replaced surgical
      procedures for the relief of central airway obstructions. RECENT FINDINGS: A
      pulmonary stent can provide immediate relief of symptoms and improvement in
      pulmonary function for both intrinsic and extrinsic airway lesions. The current
      indications for the use of both silicone-rubber stents and expandable metal
      stents are reviewed. Considerations for the anesthetic management of patients
      undergoing pulmonary stent placement are also discussed. SUMMARY: Tracheo
      bronchial stenting procedures are being employed with increasing frequency. The
      practicing anesthesiologist must be familiar with the management of patients
      undergoing airway stenting procedures.

PMID- 17021445
TI  - Preload indexes in thoracic anesthesia.
AB  - PURPOSE OF THE REVIEW: An adequate cardiac preload is essential in the treatment
      of critically ill patients. During anesthesia for thoracic surgery, volume and
      vasoactive therapy to optimize cardiac output, oxygen delivery (tissue perfusion)
      and to avoid pulmonary edema is a central therapeutic aspect. Cardiac preload has
      been estimated with different techniques in clinical practice, even though
      studies performed on thoracic anesthesia are lacking. RECENT FINDINGS: We analyze
      the conventional pulmonary artery catheter, transesophageal echocardiography and
      the transpulmonary indicator dilution technique as preload monitoring devices
      with their indications and limits in thoracic anesthesia. SUMMARY: The pulmonary
      artery catheter is confirmed as a fundamental device particularly in patients
      with pulmonary hypertension. For transesophageal echocardiography monitoring, the
      dependency on operator experience, the low repeatability and the high costs limit
      its interpretation and diffusion in clinical practice. During lung
      transplantation, Swan Ganz catheter monitoring is recommended. The optimization
      of fluid balance and vasoactive drug administration based on volumetric
      monitoring makes the transpulmonary indicator dilution technique a new option as
      an effective monitoring system during anesthesia for thoracic surgery when
      intravascular volume management is a primary objective.

PMID- 17021446
TI  - Current world literature.

PMID- 17021447
TI  - Treatment of sepsis and septic shock: is there a light at the end of the tunnel?
AB  - PURPOSE OF REVIEW: For years, the field of sepsis research was extremely active;
      the net result, however, was rather disappointing. Sepsis is still a major
      problem in intensive care units worldwide. Frustratingly, sepsis is characterized
      by a high morbidity and mortality. Although multiple (animal) studies with
      promising results have been published, the clinical situation has changed only a
      little. However, the recent 2 or 3 years of sepsis research brought significant
      results that will have a significant impact on clinical routine. RECENT FINDINGS:
      In the last 2 years, three big randomized controlled clinical trials were
      published on treatment of sepsis, each leading to a significant improvement in
      outcome: administration of activated protein C, administration of low dose
      corticosteroids, and maintenance of strict normoglycemia. SUMMARY: A breakthrough
      in sepsis research was long awaited. Recent clinical studies demonstrated that an
      improvement in outcome can be achieved even with simple means. This review
      focuses on these new therapeutic concepts, hopefully helping to transfer
      scientific advantages into everyday clinical routine.

PMID- 17021448
TI  - Extracorporeal life support for severe adult respiratory failure.
AB  - PURPOSE OF REVIEW: The past 35 years have provided a wealth of evidence that
      mechanical ventilation, although potentially life saving, can injure the lungs.
      Recent evidence suggests that limiting ventilating gas volumes can reduce patient
      mortality, but may result in progressive parenchymal derecruitment and alveolar
      hypoventilation, potentially aggravating systemic hypercarbia and hypoxemia. This
      review summarizes the current recommendations on a controversial, invasive
      technique termed 'extracorporeal life support' as a means to provide temporary
      pulmonary support during 'lung-protective' strategies. RECENT FINDINGS:
      Extracorporeal life support has been implemented since the origins of
      cardiopulmonary bypass in the 1950s, but differs in several important ways from
      cardiopulmonary bypass, including its prolonged duration of application. Because
      extracorporeal life support serves only to supplement physiological derangements
      and is not therapeutic, patient selection critically impacts results. Whereas
      reversible neonatal processes such as meconium aspiration and persistent fetal
      circulation have fostered clinical trials demonstrating the efficacy of
      extracorporeal life support, adult cardiopulmonary failure extracorporeal life
      support trials have proved less compelling. Despite two prospective randomized
      trials that failed to demonstrate its efficacy, adult extracorporeal life support
      continues in limited centers of excellence. Adult extracorporeal life support
      survival rates for respiratory failure average 50% when strict criteria are met,
      but it remains unclear whether these results represent improved outcomes.
      SUMMARY: Extracorporeal life support is an invasive technique that can provide
      support to the failing lung. Clinical trials have demonstrated its efficacy in
      neonatal and pediatric patients, but data in adults are less clear. An ongoing
      trial in the UK will soon address this important issue.

PMID- 17021449
TI  - Sedation and analgesia in the intensive care unit.
AB  - PURPOSE OF REVIEW: Sedation and analgesia are important means of providing care
      for the critically ill patient. RECENT FINDINGS: It is now clear that
      posttraumatic stress disorders resulting from an intensive care unit stay may be
      prevented by the right level of sedation. New drug developments but also recent
      findings in new ventilation strategies allow for a sedation management that is
      better tailored to an individual's need. Most importantly, regular definition of
      the appropriate level of sedation and analgesia as well as monitoring of the
      desired level will help to avoid over- and undersedation and may ultimately
      improve the outcome of the patient and reduce costs. SUMMARY: Sedation and
      analgesia are now regarded as an integral part of treatment on the intensive care
      unit instead of being an unpleasant but necessary and minor issue. The importance
      of monitoring the level of sedation and analgesia has only recently been
      realized. It remains to be shown that new management strategies including an
      evaluation of the patient, planned interventions and the choice of drugs will
      further improve the care for the critically ill.

PMID- 17021450
TI  - Postoperative pulmonary complications.
AB  - PURPOSE OF REVIEW: Postoperative pulmonary complications, including pneumonia,
      bronchospasm, respiratory failure and prolonged mechanical ventilation, occur
      commonly and are a significant source of morbidity and mortality. This review
      will discuss the etiology of postoperative pulmonary complications and the
      interventions that reduce their risk. RECENT FINDINGS: General anesthesia and
      surgery produce changes in the respiratory system and are responsible, along with
      underlying conditions, for postoperative pulmonary complications. Risk factors
      include upper abdominal or thoracic surgery, cigarette smoking, chronic
      respiratory disease, emergency surgery, anesthetic time of 180 min or more, age
      greater than 70 years, renal failure, poor nutritional status, and significant
      intraoperative blood loss. The inhibition of phrenic nerve output results in
      postoperative diaphragmatic dysfunction. Sleep-disordered breathing occurs after
      surgery even in patients without obstructive sleep apnea, but patients with
      obstructive sleep apnea may have a worsening of their disease after surgery. A
      clear advantage of one anesthetic technique over another in reducing
      postoperative pulmonary complications has not been demonstrated. Conflicting
      results have been obtained regarding the value of epidural analgesia in
      preventing postoperative pulmonary complications. Incentive spirometry decreases
      rates of postoperative pulmonary complications and hospital lengths of stay.
      SUMMARY: Understanding risk factors for the development of postoperative
      pulmonary complications allows targeted interventions aimed at reducing their
      frequency and severity. Further research is needed to define the role of regional
      analgesic and anesthetic techniques in reducing postoperative pulmonary
      complications, and also to define the nature of risk factors and develop better
      predictive models of patients at risk of developing postoperative pulmonary
      complications.

PMID- 17021451
TI  - Trauma resuscitation: what have we learned in the last 50 years?

PMID- 17021452
TI  - Drowning.
AB  - PURPOSE OF REVIEW: To summarize current knowledge on pathophysiology and
      treatment of drowning accidents. Studies and case reports were searched using the
      keywords drowning, near-drowning, asphyxia, hypoxia and hypothermia in
      conjunction with organ systems and specific treatment options. RECENT FINDINGS:
      Drowning is defined as death by suffocation in a liquid. In contrast, near
      drowning is defined as survival beyond 24 h after a drowning accident. Drowning
      is a frequent preventable accident with a significant morbidity and mortality in
      a mostly healthy population. In the majority of patients the primary injury is
      pulmonary, resulting in severe arterial hypoxemia and secondary damage to other
      organs. Damage to the central nervous system is most critical in terms of patient
      survival and subsequent quality of life. Therefore, prompt resuscitation and
      aggressive respiratory and cardiovascular treatment are crucial for optimal
      survival. Immediate interruption of hypoxia, aggressive treatment of hypothermia
      and cardiovascular failure are the cornerstones of correct medical treatment.
      Unfortunately, accurate neurologic prognosis cannot be predicted from initial
      clinical presentation, laboratory, radiological or electrophysiological
      examinations. SUMMARY: Several case studies have convincingly demonstrated that
      drowning victims may survive neurologically intact even after prolonged
      submersion times, in particular in cold water. Therefore, aggressive initial
      therapeutic efforts are indicated in most near-drowning victims.

PMID- 17021453
TI  - Patients on party drugs undergoing anesthesia.
AB  - PURPOSE OF REVIEW: Drug abuse, especially with designer drugs, continues to grow,
      involving a wide demographic range. Consequently, anesthesiologists may be
      involved in the care of patients under the acute and chronic influence of a
      myriad of substances. In addition to the usual physiological damage to vital
      organs (heart, lungs, kidneys, and immune system) new evidence of permanent
      damage in regions of the brain responsible for memory and pain mediation is
      emerging. As drug use continues to increase, anesthesiologists must learn to
      detect drug abusing patients and avoid known interactions. This article will
      attempt to review the recent literature on this subject. RECENT FINDINGS:
      Cocaine, marijuana, ethanol, and heroin top the list of abused drugs, alone and
      in combination. The combined effects of these drugs can be synergistic in
      creating cardiovascular instability and toxicity. Because combinations create
      synergy in dopamine and serotonin transmission, addiction is possibly faster,
      more entrenched, and more difficult to treat. Anesthesiologists are now becoming
      involved in many of the rapid detoxification procedures to combat/treat
      addiction. Only limited research has addressed the newer designer drugs, but case
      reports regarding hyperthermia, cerebral edema, cerebral vasospasm, and lethal
      interactions with commonly used medications such as beta-blockers implicate the
      need for awareness in anesthesia personnel. SUMMARY: Drug abuse continues to be a
      major problem facing our society. Anesthesiologists encounter emergency cases in
      which 'party drugs' have clearly been used, and may also be anesthetizing
      patients in whom abuse is present but unrecognized. Understanding how illicit
      drugs interact with anesthetic agents is of paramount importance.

PMID- 17021454
TI  - Helicopter trauma transport: an overview of recent outcomes and triage
      literature.
AB  - PURPOSE OF REVIEW: The purpose of this review is to assess literature pertinent
      to outcomes benefits accrued by the use of helicopter emergency medical services
      for trauma transport. A previous annotated bibliography assessed literature
      published between 1980 and 2000. The goal of this paper is to address
      developments since fall 2001, and to cast recent studies in the light of earlier
      work in an attempt to provide a long-range overview of the relevant literature.
      RECENT FINDINGS: In the year covered by this review, we identified four papers
      that directly assessed the association between the helicopter emergency medical
      services utilization and trauma outcome, and three that addressed the closely
      related issue of the helicopter emergency medical services triage
      appropriateness. An Italian study found no benefit associated with advanced
      prehospital care for patients with severe head injury. A US multicenter trial
      assessing blunt trauma transports found a substantial mortality reduction
      associated with helicopter use. Two other US studies, characterized by a similar
      'natural experiment' design of assessing mortality changes on either side of a
      timepoint at which the helicopter emergency medical services availability ceased,
      reached opposite conclusions about the benefits of the service. Recent studies
      addressing the helicopter emergency medical services utilization in terms of
      triage were characterized by varying levels of agreement with the widely held
      belief that this service is characterized by overtriage. SUMMARY: The
      preponderance of recent and previously extant evidence supports an argument that
      the helicopter emergency medical services transport is associated with
      significant benefit for some injured patients. The primary challenges at this
      time include the determination of which patients benefit and the elucidation of
      which aspects of the helicopter emergency medical services are responsible for
      any salutary effects of its utilization.

PMID- 17021455
TI  - Vasopressin in shock states.
AB  - PURPOSE OF REVIEW: There is growing evidence that in end-stage shock or during
      cardiac arrest, inappropriately low endogenous vasopressin plasma levels may be
      responsible for pathologic vasodilatation, inadequate organ perfusion, and poor
      outcome. The purpose of this article is to review recent publications featuring
      arginine vasopressin as a potent vasoconstrictor in various shock states such as
      systemic vasodilatation, severe hypovolemia, or cardiac arrest. RECENT FINDINGS:
      Several retrospective investigations give evidence that vasopressin at a dosage
      of 2-6 U/h is effective in reversing catecholamine-resistant vasodilatory shock
      due to sepsis or after cardiopulmonary bypass, but prospective randomized
      controlled trials are warranted. In experimental hypovolemic cardiac arrest or
      therapy-resistant (irreversible) hypovolemic shock, vasopressin may be an
      intriguing therapy, although human evidence is not available. Animal data gives
      strong evidence that vasopressin given during cardiopulmonary resuscitation
      improves both return of spontaneous circulation and neurological outcome.
      Clinical experience on the use of vasopressin for in-hospital cardiopulmonary
      resuscitation with short response time showed equipotency with epinephrine; in
      patients with out-of-hospital ventricular fibrillation, vasopressin showed
      improved 24 h survival in comparison with epinephrine. After the large European
      multicenter study completed in summer 2002, we will hopefully be able to better
      determine the role of vasopressin versus epinephrine in the management of adult
      cardiac arrest. SUMMARY: Vasopressin administration is emerging as a rational and
      promising therapy in the management of various shock states and cardiac arrest.

PMID- 17021456
TI  - Resuscitation and anaesthesia for penetrating trauma.
AB  - PURPOSE OF REVIEW: The worldwide burden of trauma is increasing, but is unequal
      between nations. Trauma targets the young and productive in society and imposes a
      major burden on the health infrastructure. This review provides a distillation of
      practice in a busy urban trauma centre dealing with large volumes of penetrating
      trauma. RECENT FINDINGS: The anaesthetist holds a pivotal role in the management
      of penetrating injury; the requirements of prompt airway control, early delivery
      to theatre and control of a physiologically brittle patient can be challenging.
      Recognition that attempts at definitive surgery in exsanguinating patients may do
      more harm than good has made surgery a tool of resuscitation rather than an end
      in itself. SUMMARY: Depending on where they practice, clinicians are more or less
      likely to encounter patients with gunshot wounds. However, adherence to basic
      principles and attention to the details of temperature control, invasive
      haemodynamic monitoring, blood product therapy and effective communication should
      translate to improved outcomes for patients after penetrating trauma.

PMID- 17021457
TI  - Ensuring quality in prehospital airway management.
AB  - PURPOSE OF REVIEW: Ensuring quality in prehospital airway management is
      challenging because the out-of-hospital setting is a fast-paced and unpredictable
      environment. The first step in meeting this challenge is the recognition by
      emergency medical service leaders that prehospital airway management is prone to
      error. Quality core values such as safety, effectiveness, timeliness, efficiency,
      and equity for prehospital airway management, specifically endotracheal
      intubation, will be discussed. RECENT FINDINGS: Controlled studies in prehospital
      airway management are few. In those that have evaluated the use of endotracheal
      intubation in this setting, safety issues, increased scene time, and lack of
      effectiveness to improve outcome have been revealed. SUMMARY: Emergency medical
      service administrators must critically evaluate the quality of prehospital airway
      management that they are providing to patients within their system by collecting
      the data necessary to identify quality issues and developing strategies to
      implement change. Research into other techniques that can provide ventilation and
      oxygenation to patients in the prehospital environment and that are safe and
      effective, such as laryngeal mask airway, need to be performed.

PMID- 17021458
TI  - Burn injuries.
AB  - PURPOSE OF REVIEW: To summarize new advances and research findings that relate to
      the treatment of burn victims. RECENT FINDINGS: Recent advances in burn
      resuscitation and critical care reflect a better understanding of the acute phase
      pathophysiology of severe burns. Aggressive management of the unstable burn
      airway is always the most important clinical priority. Emphasis has been placed
      on the early identification of inhalation injury and its impact on fluid
      resuscitation, as well as on a protective lung strategy to reduce the development
      of pulmonary edema, acute lung injury and pneumonia, and to reduce the risk of
      barotrauma. New blood markers, such as serum cholinesterase and inflammatory
      cytokines, have been introduced to assist in the prognosis of morbidity and
      mortality, beyond the traditional vital signs. At this time, however, these are
      available only for research purposes. Finally, early burn wound excision and
      coverage with new biodegradable materials results in less pain and more rapid
      healing for the patient. SUMMARY: The combination of innovative approaches and a
      dedicated burn team is expected to continue to improve survival in the next few
      years even in the most severe cases.

PMID- 17021459
TI  - Managing mass casualties.
AB  - PURPOSE OF REVIEW: The issue of mass casualty associated with terrorism has
      gained tremendous public interest, but only modest medical interest, in the past
      2 years. This review examines recent medical literature and outlines a practical
      approach to managing the mass casualty situation on the basis of a doctrine
      developed and extensively practised in Israeli hospitals. RECENT FINDINGS: A
      large portion of recently published articles deal with the preparedness for
      'conventional', biological or chemical mass casualty situations. Accounts of past
      events reveal serious discrepancies between well-designed contingency plans and
      the disappointing management of actual mass casualty situations. The 'Israeli
      doctrine' is a general 'master plan' for managing mass casualty situations that
      is adjusted by every hospital to its specific characteristics. Its major
      principles and features, as well as practical 'tips' are described. SUMMARY: The
      world medical community, being in the forefront of any natural or man-made
      disaster, should prepare itself for its effective management. Contingency plans
      should be comprehensive, and should follow certain general guidelines, but should
      be specific for different causes of mass casualty situations and be adjusted to
      each medical system or hospital. Medical personnel should become familiar with
      these plans through repeated drills. Experience gained in actual mass casualty
      events should be analysed and published to improve contingency plans and their
      implementation.

PMID- 17021460
TI  - Role of the anaesthetist in developing and implementing readiness of hospital to
      mass casualty incidents.
AB  - PURPOSE OF REVIEW: A mass casualty incident is usually short and resolves itself.
      To minimize the risks to patients during mass casualty incidents, planning is
      essential. We hereby provide our experience with a recent literature review of
      the steps to provide the hospital with an efficient plan to overcome mass
      casualty situations of a traumatic nature, with special implications for the
      anaesthetist's role. RECENT FINDINGS: Preparation of the hospital starts with an
      accepting master plan and guidelines for creating local standing orders for this
      scenario. The hospital should work step by step in adjusting the master plan to
      its local requirements and infrastructure. During this work, one will find that
      it is not only technical or logistic but should address medical issues, with
      pertinent information from clinicians of different specialities. After
      authorization of the preparedness plan, it should be tested in limited scale
      drills, and then implemented in the hope that it will never need to be used.
      Periodic adjustments according to threats and new concepts and equipment should
      be made. SUMMARY: As a result of recent events, a major effort is considered to
      improve the preparedness plan of the hospital for mass casualty incidents.
      However, common surveyors report their unease with the current ability to cope
      with disasters. The involvement of medical teams in the process is mandatory to
      lessen the effects of the first wave of casualties and to be able to cope with
      the second wave.

PMID- 17021461
TI  - Informed consent for children.
AB  - PURPOSE OF REVIEW: Consent has always been an essential element in the physician
      child/parent relationship, more importantly as an ethical duty than as a legal
      requirement, and continues to represent the most important form of communication
      between children and parents and physicians. RECENT FINDINGS: The main themes
      described in this review - the age of competence to give consent and the role of
      the parents in giving consent - constitute the complex situation of consent in
      paediatrics. Refusal by children and parents and consent by children for
      participation in clinical research studies are also discussed. SUMMARY: This
      review supports the moral viewpoint that minors with decision-making capacity,
      regardless of their age, should be involved in their healthcare decisions, even
      if the law is to have consent from parents or legal guardians.

PMID- 17021462
TI  - Should do-not-resuscitate orders be suspended for surgical cases?
AB  - PURPOSE OF REVIEW: There are significant misunderstandings about the management
      of perioperative do-not-resuscitate orders. This paper reviews some of the
      difficulties generated by the halting acceptance and inconsistent implementation
      of an ethically appropriate perioperative do-not-resuscitate policy that mandates
      reconsideration of existing do-not-resuscitate orders. It also offers strategies
      for empowerment of such a policy. RECENT FINDINGS: Recent advances in the ethical
      practice of anesthesiology have centered on determining and correcting why
      perioperative do-not-resuscitate policies are poorly accepted, and how to
      establish a hospital-wide adherence to such policies. Barriers to ethically
      appropriate application of perioperative do-not-resuscitate orders include
      differing values and misunderstandings between physicians and their patients -
      and also between anesthesiologists and other physicians - as well as medicolegal
      concerns. Policies should be designed and implemented at the level of the
      healthcare institution, and they must be sufficiently flexible to permit the
      tailoring of the perioperative do-not-resuscitate order to the autonomous choice
      of the patient. Such policies should state unambiguously that existing do-not
      resuscitate orders are to be reevaluated, delineate responsibilities for
      reconsidering the do-not-resuscitate order, state available options, define
      necessary documentation, and list resources for help. SUMMARY: A well written
      perioperative do-not-resuscitate policy is essential for surmounting obstacles to
      a well functioning perioperative do-not-resuscitate system.

PMID- 17021463
TI  - Ethical issues and the role of anesthesiologists in non-heart-beating organ
      donation.
AB  - PURPOSE OF REVIEW: Demand for vital organs for transplantation continues to
      increase, and the supply of organs has not kept up with demand. The use of organs
      harvested immediately after death from patients who have requested withdrawal of
      life support may be one way to increase supply. Anesthesiologists frequently
      become involved with such 'non-heart-beating' organ donations when they are asked
      to withdraw life support from patients in the operating room and monitor them,
      providing terminal care, until death ensues. RECENT FINDINGS: Despite thorough
      debate in the literature and reviews by the Institute of Medicine, ethical
      controversies remain concerning the use of non-heart-beating donors. Further, non
      heart-beating organ donation has failed to produce the windfall of vital organs
      for transplant predicted by optimistic early estimates. There is agreement in the
      medical specialties of palliative care, intensive care medicine, internal
      medicine, and family practice that competency in end-of-life care requires
      specialty training. Most anesthesiologists are poorly qualified to carry out the
      tasks involved in non-heart-beating donation, and may even potentially compromise
      care. SUMMARY: Ethical controversies in the use of non-heart-beating donors
      remain despite thorough review. No physician should be involved in withdrawal of
      life support in non-heart-beating donors, unless specialty trained in end-of-life
      care. Most anesthesiologists should not be involved in non-heart-beating organ
      donations; potential exceptions include those with specialty training or
      experienced in palliative care or intensive care medicine.

PMID- 17021465
TI  - Current world literature.

PMID- 17021464
TI  - End-of-life decisions during intensive care treatment.
AB  - PURPOSE OF REVIEW: End-of-life decisions play an important role in the intensive
      care unit. This review discusses the most important studies on end-of-life
      decisions published from October 2001 to October 2002. RECENT FINDINGS: Refusal
      of admission to the intensive care unit in itself is frequently an end-of-life
      decision. However, some patients survive rejection. The main end-of-life
      decisions during intensive care unit stay are withholding or withdrawal of
      therapy. Some patients have do-not-resuscitate orders on admittance to a unit.
      The effect of family participation and involvement of other caregivers in such
      decisions has been extensively studied. Such participation can lead to anxiety
      and depression in the family. A procedural guideline for decision making is of
      clinical interest. The background of physicians plays an important role. Terminal
      sedation and analgesia play an important role in execution of end-of-life
      decisions. During intensive care unit admission there is a continuous change in
      circumstances, which causes continuous differences in the wishes of the patients
      and relatives. The small contribution of the cost of the last days of life to
      total healthcare cost was reconfirmed. SUMMARY: The new studies put emphasis on
      the facts that all care providers should participate in the decision and that
      communication with surrogates is of extreme importance. Many valid points from
      other medical fields also apply to the intensive care unit situation.

PMID- 17021466
TI  - Management of hypotension in obstetric anesthesia: is it time to re-write the
      textbooks?

PMID- 17021467
TI  - Fetal assessment: do newer technologies offer better assessment and outcomes?
AB  - PURPOSE OF THE REVIEW: The present manuscript reviews recent data on fetal
      intrapartum surveillance with special attention to new technologies. RECENT
      FINDINGS: Continuous fetal heart-rate monitoring, fetal blood sampling,
      intrapartum stimulation tests, fetal pulse oximetry and fetal electrocardiography
      will be reviewed. SUMMARY: From the available data it appears that to date the
      analysis of the sinus tachycardia segment of the fetal electrocardiography used
      in conjunction with continuous fetal heart-rate monitoring is the method of
      choice.

PMID- 17021468
TI  - Amniotic fluid embolus: can we affect the outcome?
AB  - PURPOSE OF REVIEW: Amniotic fluid embolism is a rare catastrophe unique to
      pregnancy. Its mortality rate remains high despite efforts at prompt and
      aggressive management protocols, highlighting the need to maintain a high index
      of suspicion. RECENT FINDINGS: The intrusion of amniotic fluid into the maternal
      bloodstream may lead in certain women to a complex series of physiological
      reactions mimicking those seen in human anaphylaxis or sepsis, negating the
      purely embolic phenomenon theory as previously understood. The clinical picture
      is the sudden onset of cardiovascular collapse, cyanosis, haemorrhage or
      disseminated intravascular coagulopathy, during or soon after delivery. SUMMARY:
      The mainstay of a successful outcome remains the identification of high-risk
      patients, as well as early clinical diagnosis and management.

PMID- 17021469
TI  - Pregnancy, delivery and the intensive care unit: need, outcome and management.
AB  - PURPOSE OF REVIEW: Increasing numbers of sick pregnant and peripartum women are
      cared for in the intensive care unit. This review looks at the current mortality,
      the disease severity of admitted patients and the current need for intensive care
      unit and high dependency unit beds to cater for these women. It also looks at
      some recent advances in the treatment of some specific disease entities
      encountered in the intensive care unit in pregnant women and parturients which
      have been covered in the 2001-2002 literature. RECENT FINDINGS: There has been a
      substantial fall in intensive care unit mortality in the last decade and there is
      a definite place for these women in intensive care unit. They represent a
      subgroup of severely ill patients with a need for intensive treatment and
      monitoring and who are worth the investment in time and money because they often
      recover from their acute illness to return to full productivity. SUMMARY: The
      high dependency unit and intensive care unit and their role in the service to the
      pregnant woman and parturient are the main focus of this review which looks at
      the last 2 years' literature to determine the critical care services' worth and
      efficacy. In almost all countries, even in the smaller regional hospitals, the
      intensive care units and high dependency units have reduced maternal mortality
      and morbidity. The neonatal high dependency units have done much the same for the
      newborn but the neonatal literature is not reviewed for the purposes of this
      symposium.

PMID- 17021470
TI  - Backaches related to pregnancy: the risk factors, etiologies, treatments and
      controversial issues.
AB  - PURPOSE OF REVIEW: There is no clear documentation in either the anesthetic/pain
      or obstetric literatures regarding the management of backache related to
      pregnancy. Backache can occur during pregnancy, in labor, and postpartum;
      different stages should be managed differently. The purpose of this review is to
      discuss the different types of backache, to provide an overview of diagnosis and
      treatment options, and to address several controversial issues related to
      pregnancy-related backaches. RECENT FINDINGS: Gestational backache is a
      substantial problem and can have a significant impact on a pregnant woman's daily
      activities. Non-pharmacological/complementary treatments such as posture
      adjustment, acupuncture, physical therapy, physiotherapy, yoga, and chiropractic
      may become the first line of treatment options. In labor backache the posture of
      the parturient can have an effect in decreasing the intensity of pain. Allopathic
      medicine, regional techniques (epidural), and complementary interventions are
      routinely given to parturients. However, there is a major perception of
      differences among midwives, obstetricians and anesthesiologists in terms of the
      risks and benefits of labor epidural analgesia. Postpartum backache is usually
      self-limited, but for some mothers the pain can last from a few months to several
      years. Early literature suggested that this problem was associated with the use
      of epidurals, but recent data in the literature deny such an association.
      SUMMARY: Overall, backache related to pregnancy is a significant problem.
      Education is still the first line of intervention for preventing backaches
      related to pregnancy. Both allopathic and complementary medicines are frequently
      used as treatments for backache related to pregnancy.

PMID- 17021471
TI  - Chronic pelvic pain in women of childbearing age.
AB  - PURPOSE OF REVIEW: The purpose of this article is to summarize new findings in
      the area of chronic pelvic pain in women of childbearing age. RECENT FINDINGS:
      Particular attention over the past few years has been paid to the
      multidisciplinary approach in diagnosing and treating chronic pelvic pain,
      because it is common knowledge that different medical specialties very often deal
      with patients affected by this condition. SUMMARY: A classification of chronic
      pelvic pain is presented, along with the recommended evaluation, diagnostic
      investigations, and treatment of this condition, based on recent reports in the
      literature.

PMID- 17021472
TI  - Ontogeny of receptors relevant to anesthesiology.

PMID- 17021473
TI  - Propofol in paediatric anaesthesia.
AB  - PURPOSE OF REVIEW: In this review we intend to ascertain trends in propofol
      administration for paediatric anaesthesia and sedation. RECENT FINDINGS: Propofol
      is being 'discovered' by non-anaesthesiologist practitioners of paediatric
      sedation. However it appears that the drug is not infrequently administered alone
      for painful procedures, necessitating large doses that result in uncontrolled
      general anaesthesia with a high potential for adverse events. An elegant
      technique comprises small doses of short-acting opioid (e.g. fentanyl 1 mug/kg)
      with low-dose propofol infusion. This does not result in worsening of pre
      existing right-to-left intracardiac shunts. The dilemma is to educate non
      anaesthesiologists about propofol pharmacokinetics and pharmacodynamics and in
      particular about the advantages of combined drug therapy. A paediatric target
      controlled system for propofol has undergone preliminary clinical evaluation and
      it is hoped that administration according to pharmacokinetic principles will
      refine administration to infants and children. Sporadic cases of the propofol
      infusion syndrome in patients receiving prolonged sedation in intensive care
      units continue to be reported (characterized by metabolic acidosis,
      rhabdomyolysis and myocardial failure). It appears that one mechanism may be a
      deficiency of mitochondrial oxidative processes possibly induced by a dialyzable
      substance, perhaps a propofol metabolite. Propofol has been used with some
      success in treating postoperative laryngospasm and for tracheal intubation
      without muscle relaxants. SUMMARY: Propofol should be used with extreme caution
      for prolonged sedation in intensive care unit patients, at dose rates of below 5
      mg/kg per h, while maintaining extreme vigilance for signs of developing propofol
      infusion syndrome. If used correctly propofol is a suitable drug for sedation
      outside the operating room.

PMID- 17021474
TI  - Central venous catheter techniques in infants and children.
AB  - PURPOSE OF REVIEW: The placement of central venous catheters is often necessary
      to facilitate optimal anaesthetic and perioperative management or for the long
      term management of chronic underlying diseases. Insertion may be a challenge in
      selected patients, and the risk of infection, thrombosis, and other complications
      may result in significant risk factors. RECENT FINDINGS: Ultrasound visualization
      of the cervical veins with Valsalva manoeuvres significantly increases the rate
      and safety of central venous cannulation, and decreases needle passes in
      paediatric patients even with experienced operators. Pericardial effusion with
      tamponade is a more frequent phenomenon than generally realized, and accurate
      location of the catheter-tip position is essential. The femoral venous approach
      has proved to be safe even in premature babies. Clear guidelines for infection
      control and the prevention of intravascular catheter-related infections in
      children have been established; however, the high incidence of nosocomial
      catheter-related infections requires effective prevention strategies. The impact
      of antimicrobial-impregnated central venous catheters on the prevention of
      bloodstream infections in children is not yet clear. Routine use of prophylactic
      antibiosis (i.e. vancomycin) to prevent catheter-related infection cannot be
      recommended. Thrombolytic therapy with recombinant tissue plasminogen activator
      is safe, efficient, well tolerated and effective for lysis of catheter-induced
      intravascular and intracardiac thrombi even in neonates. Embolized catheter
      fragments can be retrieved in neonates and children by non-surgical interventions
      using standard procedures applied by paediatric cardiologists. SUMMARY: Despite a
      variety of new techniques, the major problem of central venous catheterization in
      neonates and children remains the prevention of catheter-related infection and
      infection control.

PMID- 17021475
TI  - Ropivacaine in infants and children.
AB  - PURPOSE OF REVIEW: Ropivacaine is considered less toxic than bupivacaine. In
      addition, at the low concentrations used for providing postoperative analgesia,
      ropivacaine seems to produce less motor blockade than bupivacaine. These two
      properties are of particular interest in paediatric practice. RECENT FINDINGS: In
      paediatric practice regional anaesthesia is usually performed under general
      anaesthesia, and postoperative analgesia was until recently the major concern for
      most practitioners. The question now is: what is the right concentration to
      provide adequate intraoperative anaesthesia when ropivacaine is used in
      combination with volatile anaesthetic agents? The low concentration of
      ropivacaine used for postoperative analgesia seems to provide adequate
      intraoperative anaesthesia when general anaesthesia with a 0.5 minimum
      concentration of volatile anaesthetic is used in combination. However, potential
      toxicity is still the subject of debate because ropivacaine clearance is low in
      infancy and early childhood. Ropivacaine has a longer absorption process than
      bupivacaine, which leads to a lower maximum peak concentration with ropivacaine
      than with bupivacaine either after central or peripheral blocks, thus increasing
      the safety of the drug. The addition of adjuvant drugs also permits lower
      concentrations of ropivacaine, while providing excellent analgesia. The addition
      of adrenaline at very low concentrations has recently been found to increase the
      quality of epidural analgesia. SUMMARY: Ropivacaine is now the reference drug for
      regional anaesthesia in paediatric patients, mainly because it is considered less
      toxic than bupivacaine and provides excellent postoperative analgesia even when
      used at low concentrations.

PMID- 17021476
TI  - Postoperative analgesia in infants and children.
AB  - PURPOSE OF REVIEW: Although postoperative analgesia in infants and children
      should be an integral part of the perioperative management, undertreatment of
      pain is not rare in clinical practice and may influence outcome and long term
      behaviour. Therefore, this review summarizes results of recent papers and
      discusses actual trends and future perspectives concerning postoperative
      pharmacologic pain therapy in infants and children. RECENT FINDINGS: A multimodal
      approach using locoregional anesthesia and systemic analgesics is a widely
      accepted technique. New developments include new local anesthetics with a wider
      margin of safety and more experience with adjuvants, catheter techniques and
      systemic analgesics. Replacement of bupivacaine with ropivacaine may be prudent
      especially for prolonged epidural infusion, use in neonates, impaired hepatic
      metabolic function, and anesthetic techniques requiring large dosage of local
      anesthetic. The limited duration of analgesia after single blocks can be
      prolonged by use of adjuvants (clonidine, ketamine), catheter techniques or early
      use of systemic analgesics. Non-opioids (acetaminophen, non-steroidal anti
      inflammatory drugs) are appropriate for patients with mild to moderate pain or as
      a component of multimodal pain therapy. Patient- and nurse-controlled analgesia
      are convenient ways for opioid administration in infants and children. SUMMARY:
      The reviewed studies suggest that there are many reliable agents and techniques
      available to provide a safe and effective postoperative analgesia even in
      neonates and small infants.

PMID- 17021478
TI  - Airway expert or expert in airway management?

PMID- 17021477
TI  - Awake spinal or caudal anaesthesia in preterms for herniotomies: what is the
      evidence based benefit compared with general anaesthesia?
AB  - PURPOSE OF REVIEW: Postoperative apnoea is known to threaten preterm and ex
      preterm infants undergoing surgery for inguinal hernia. Awake regional
      anaesthesia, initially spinal and later caudal anaesthesia have been suggested as
      effective techniques to avoid these complications. However, most herniotomies in
      this group of patients are still performed under general anaesthesia without
      deleterious consequences. Whereas some experts continue to claim advantages for
      awake regional over general anaesthesia for preterm infants, others consider
      awake regional anaesthesia to be an exclusive, technically difficult and
      unreliable technique of unconfirmed benefit. RECENT FINDINGS: It is appropriate
      to weigh the scarce available evidence that has been accumulated since 1984, and
      put it into perspective with new developments in paediatric general anaesthesia.
      The actual clinical significance of postoperative apnoea and improvements in
      neonatal and perioperative care and monitoring must also be reconsidered.
      SUMMARY: The available evidence does not allow unequivocal conclusions to be
      drawn or recommendations to be made. Awake regional anaesthesia for herniotomies
      in preterm infants has been found to be superior in most studies; however, it
      requires technical expertise and dedication on the part of the anaesthetist and
      surgeon. When light general anaesthesia with modern anaesthetic agents such as
      sevoflurane or desflurane is combined with a caudal block, postoperative apnoea
      is very rare, and can easily be recognized and managed with good postoperative
      monitoring and therapy.

PMID- 17021479
TI  - Anaesthetic considerations in patients with chronic pulmonary disease.
AB  - PURPOSE OF REVIEW: Chronic pulmonary diseases are getting more important in daily
      anaesthetic practice, because prevalence is increasing and improved anaesthetic
      techniques have led to the abandonment of previous contraindications to
      anaesthesia. It is therefore essential for the anaesthetist to be up to date with
      current clinical concepts and their impact on the conduction of anaesthesia as
      well as new insights into how to anaesthetise these patients safely. RECENT
      FINDINGS: If patients are treated adequately, open and minimally invasive
      operations can be safely performed under regional and general anaesthesia. The
      management of acute exacerbations remains challenging, and first-line medical
      treatment should be supported by non-invasive ventilation. In controlled
      mechanical ventilation, parameters should be set to avoid dynamic hyperinflation.
      SUMMARY: Assessing the functional status of patients admitted for surgery remains
      a difficult task, and in patients identified as being at risk by clinical
      examination additional spirometry and blood gas measurements may be helpful. If
      there are flow limitations and signs of respiratory failure, the anaesthetist
      should be highly alarmed and monitor the patient closely and invasively, yet
      there is no reason to deny any patient a substantially beneficial operation.

PMID- 17021480
TI  - Recent advances in the treatment of pulmonary hypertension.
AB  - PURPOSE OF REVIEW: Pulmonary hypertension is a debilitating life-threatening
      disease of all ages. The long-term prognosis can be dismal despite maximal
      medical therapy. There have been significant advances in our understanding of the
      pathobiology and genetics of this disease, and novel pharmacological approaches
      appear to offer promising alternatives to conventional therapy. Anesthesiologists
      have been instrumental in the development and widespread clinical introduction of
      inhaled nitric oxide. Unfortunately, despite early optimism, inhaled nitric oxide
      has several significant limitations related to its cost, toxicity, required
      complex technology, and occasional therapeutic failure. Therefore, there is a
      need for an effective alternative pulmonary vasodilator. The early diagnosis and
      treatment of pulmonary hypertension are crucial if improvements are to be
      realized. This review will present recent work in this field in an attempt to
      increase anesthesiologists' awareness of potential new treatment options. RECENT
      FINDINGS: Emerging data concerning the genetics of certain pulmonary hypertension
      variants have provided insight into the pathobiology of this disease and may lead
      to advances in the early detection or new treatment options. New pharmacological
      approaches include drugs such as nitric oxide donors, phosphodiesterase
      inhibitors, endothelin antagonists, and prostacyclin analogues. Attention has
      also been focused on the use of combinations of drugs of different classes.
      SUMMARY: The clinical outcome of pulmonary hypertension is dependent upon early
      detection and therapy. Increased awareness of current therapeutic options will
      facilitate earlier effective treatment.

PMID- 17021481
TI  - Cerebrovascular disease.
AB  - PURPOSE OF REVIEW: Carotid endarterectomy remains the preferred surgical
      intervention for the prevention of stroke among patients with extracranial
      cerebrovascular disease. Subgroup analyses of the results of several multicentre
      trials have contributed substantially to our understanding of the appropriate
      selection of patients and the perioperative risk associated with this procedure.
      RECENT FINDINGS: This review describes recent advances in our understanding of
      the appropriate use of carotid endarterectomy, and outlines recent developments
      and strategies that are likely to influence the perioperative care of these
      patients. SUMMARY: As current clinical guidelines for the use of carotid
      endarterectomy unfold, anaesthesiologists can expect to care more frequently for
      older patients and those at increased risk of complications. The perioperative
      management of co-existing diseases, particularly the control of hypertension and
      the strategies aimed at reducing the risk of cardiac complications, will
      contribute substantially to reducing perioperative morbidity and mortality.

PMID- 17021483
TI  - Current world literature.

PMID- 17021482
TI  - Carcinoid tumor and carcinoid syndrome.
AB  - PURPOSE OF REVIEW: Carcinoid tumors secrete many different types of substances
      (e.g. serotonin, bradykinin) that may produce potentially fatal intraoperative
      reactions such as hypotension and bronchoconstriction. The most effective
      treatment for the deleterious cardiovascular and pulmonary effects of serotonin
      and bradykinin is octreotide, a somatostatin analogue. Carcinoid heart disease,
      which develops in the majority of patients with carcinoid syndrome, presents the
      anesthesiologist with more diagnostic and therapeutic dilemmas. RECENT FINDINGS:
      The incidence of carcinoid tumors is much greater than previously recognized. New
      diagnostic techniques permit identification and localization of carcinoid tumors
      with greater accuracy. Short term and long term therapy with octreotide
      significantly improves survival and reduces the severity of 'carcinoid crises'.
      Echocardiographic studies have demonstrated a very high incidence of carcinoid
      heart disease (tricuspid and pulmonary insufficiency) in patients with carcinoid
      syndrome. Cardiac valve surgery is, consequently, becoming much more common in
      patients with carcinoid syndrome. SUMMARY: More patients with carcinoid tumors
      and carcinoid syndrome are requiring anesthesia and surgery. Specific therapy
      with somatostatin analogues (octreotide) has replaced older less specific drugs
      (e.g. antihistamines) for the treatment of adverse effects caused by products of
      carcinoid tumors.

PMID- 17021484
TI  - Remifentanil: an update.
AB  - PURPOSE OF REVIEW: Remifentanil has now reached maturity, as reflected by the
      increasing number of clinical papers relating to its use. Its position among
      anaesthetic drugs is now better understood, and this review will attempt to place
      it in the context of current clinical practice. RECENT FINDINGS AND SUMMARY:
      Propofol reduces the initial distribution of remifentanil, leading to higher
      concentrations during induction. Propofol and remifentanil administered together
      at sedative doses display a major synergistic interaction on the respiratory
      drive. Remifentanil accelerates the penetration of sevoflurane to its site of
      effect. The risk of intraoperative awareness seems to be low when remifentanil is
      associated to very low concentrations of hypnotic drugs, but this field warrants
      further investigation. Acute tolerance to opioids and its prevention remain
      controversial. SUMMARY: Remifentanil is the opioid of choice for tracheal
      intubation without muscle relaxants. It provides an alternative to regional
      anaesthesia in labour pain control. Target-controlled infusion may further
      improve the administration of remifentanil.

PMID- 17021485
TI  - Implication of aging on anesthetic drugs.
AB  - PURPOSE OF REVIEW: The elderly population is increasing in number each year, and
      more patients are presenting for anesthesia and surgery. One of the key areas for
      improving the care of the elderly is a better understanding of the influence of
      aging on drug pharmacokinetics and dynamics. RECENT FINDINGS: We now know more
      about the effects of risk factors on the occurrence of postoperative
      complications, and strategies to improve outcome after anesthesia and surgery.
      Two such strategies include the role of perioperative beta-adrenoceptor blockade
      in obtunding cardiovascular responses and myocardial ischaemia, and the provision
      of effective perioperative analgesia. Both topics have featured in key
      publications during the past year. Cognitive dysfunction following surgery occurs
      in about 10% of elderly patients; possible etiologies include a decline in
      central nervous system cholinergic function. One major disease of the elderly is
      Parkinson's disease, which offers challenges to the anesthesiologist both with
      regard to alterations of physiology and in choice of anesthetic drugs and
      techniques. SUMMARY: The effects of comorbidity and intercurrent medications may
      alter the normal anesthetic practice of the clinician's care of the elderly
      patient. Further studies in these key areas may lead to improved outcomes.

PMID- 17021486
TI  - Should a patient's gender alter the anesthetic plan?
AB  - PURPOSE OF REVIEW: A significant effort has been made in the past few years to
      determine whether a patient's gender has a significant effect on their anesthetic
      requirements or outcome. It remains unclear whether there is sufficient evidence
      to alter an anesthetic regimen based on a patient's gender. RECENT FINDINGS: In
      well-controlled studies, subtle pharmacokinetic differences between the sexes can
      be observed. Pharmacodynamic differences have also been observed between the
      sexes, particularly for muscle relaxants and opioids. Outcome studies have
      revealed that women are also more likely to experience adverse side-effects such
      as postoperative nausea. SUMMARY: There are subtle differences between men and
      women. However, these differences are of a similar magnitude to those that may
      exist between other commonly encountered factors, such as smoking versus non
      smoking, occasional versus regular ethanol consumption, or perhaps, most
      importantly, the increased age of the patient. If these are combined with pre
      existing medical conditions and other patient variables, such as ethnicity, the
      potential gender effect on anesthesia may easily be overshadowed.

PMID- 17021487
TI  - Optimizing intraoperative fluid therapy.
AB  - PURPOSE OF REVIEW: Correcting the fluid status of the surgical patient is an
      integral part of good anaesthetic practice. There have been few areas in
      anaesthesia and perioperative medicine as controversial as fluid resuscitation.
      Uncertainties still exist as to what the best solution to give is, whether it be
      a colloid or a crystalloid, and how and when to give it. As well as increasing
      awareness of the different properties of various colloids, there has been
      interest in the nature of the carrier solutions, essentially a choice between
      saline or Ringer's lactate (compound sodium lactate or Hartmann's solution). In
      this article we review recent studies involving crystalloids, the 'new colloids',
      and on the amount and timing of fluid therapy. RECENT FINDINGS: Saline based
      fluids (including most colloids) are associated with a hyperchloremic metabolic
      acidosis, and a hypocoagulable state, although these may not necessarily harm the
      patient. Saline may have deleterious effects on renal function. Colloids in
      solutions similar to Ringer's lactate ('balanced solutions') may avoid these
      effects although few are currently available. Several studies that have used
      fluids (along with other therapies) to improve organ perfusion around the time of
      surgery have been associated with a better outcome. SUMMARY: Compared with
      Ringer's lactate, saline, and saline-based colloids are associated with a
      hyperchloremic metabolic acidosis, and a hypocoagulable state although they may
      not be associated with adverse patient outcomes. Increasing awareness of the
      'Stewart hypothesis' has led to new ways of managing hyperchloremic metabolic
      acidosis. The 'crystalloid-colloid debate' continues, and has led to an awareness
      that these different fluids, along with their carrier solutions are drugs with
      different effects. Several studies, in which patients have received more fluid in
      the protocol group, have found better clinical outcomes in the 'optimized'
      patients.

PMID- 17021488
TI  - Brachial plexus blocks: infusions and other mechanisms to provide prolonged
      analgesia.
AB  - PURPOSE OF REVIEW: Regional anesthesia has numerous benefits for upper extremity
      surgery such as improved analgesia, opioid sparing and reduced side effects.
      However, many of these advantages are lost after block regression. Recently,
      several strategies such as continuous ambulatory local anesthetic infusions and
      adjuvants that may potentiate analgesia after a brachial plexus block have been
      described and investigated. This review will highlight and place in context this
      recent work. RECENT FINDINGS: Current investigations have demonstrated that
      brachial plexus analgesia can be extended by combining existing solutions and
      technology. This has been most evident in the use of ambulatory continuous
      peripheral nerve blocks such as the interscalene, infraclavicular and axillary
      approaches. Accomplishing this safely in an outpatient setting requires the use
      of basic infusion pumps, patient education and a mechanism for follow-up after
      discharge. This strategy has prolonged pain relief and facilitated major
      operations on an outpatient basis. An alternative to this strategy is to combine
      adjuvants such as opioids, clonidine, ketamine and neostigmine to potentiate the
      effects of local anesthetics. These additives have had mixed results. The most
      promising solutions are the alpha-2-adrenergic agonists but further investigation
      is necessary to confirm their efficacy and quantify their appropriate dose and
      side effects. SUMMARY: The advances and techniques recently described demonstrate
      that prolonging analgesia after brachial plexus blocks is possible. This may be
      accomplished via several different approaches and mechanisms resulting in
      improved patient analgesia and side effects.

PMID- 17021489
TI  - The anaesthesiologist in the intensive care unit.
AB  - PURPOSE OF REVIEW: This review focuses on recent knowledge in areas of
      anaesthesia expertise which are indispensable to intensive care unit management,
      including airway management, vascular access, regional analgesia and the
      treatment of status asthmaticus and status epilepticus. RECENT FINDINGS:
      Etomidate as the sole agent for intubation in the intensive care unit has a 90%
      success rate, while in a prehospital setting, the addition of succinylcholine to
      etomidate results in a 99% success rate. In determining successful intubation,
      capnography and laryngoscopic/fibreoptic visualization are superior to
      auscultation, while auscultation is as effective as the self-inflating bulb or
      transillumination with the lightwand. The dorsalis pedis artery is an effective
      alternative to radial artery cannulation, while arterial cannulation itself can
      result in major adverse effects if complications arise. Ultrasound guidance in
      the placement of central catheters results in an improved insertion success rate.
      Internal jugular and subclavian lines have similar risk of haemothorax or
      pneumothorax, while subclavian lines are associated with the lowest incidence of
      infection. Midazolam, thiopentone and propofol have all been found to be
      efficacious in terminating refractory status epilepticus, with thiopentone
      resulting in a lower incidence of breakthrough seizures or treatment failure but
      an increased incidence of hypotension. Inhalational anaesthesia using isoflurane
      or desflurane has also been found to be successful in refractory status
      epilepticus. In the management of status asthmaticus, limiting minute volume
      while tolerating hypercapnia and acidosis as well as the use of inhalational
      anesthesia have proven effective strategies in a number of refractory cases.
      SUMMARY: The anaesthesiologist's unique knowledge and skills are ideally suited
      to the practical management of patients in a critical care setting as well as in
      the treatment of the critical phases of many illnesses.

PMID- 17021490
TI  - Challenges facing the anesthesiologist in the emergency department.
AB  - PURPOSE OF REVIEW: This review focuses on developments in airway management and
      concious sedation/analgesic techniques employed by anesthesiologists in the
      emergency department. RECENT FINDINGS: Emergency medicine physicians routinely
      employ airway devices and techniques that were previously reserved for
      anesthesiologists. An understanding of the uses and limitations of these devices
      are essential for successful outcomes. Anesthesiologists responding to the
      emergency department may be faced with soiled or traumatized airways. The use of
      newer devices in cervical trauma and the difficult airway is reviewed. Consious
      sedation in the emergency department is also reviewed. There are no published
      recommendations demonstrating the advantage of specific agents for sedation in
      the emergency department. A wide variety of medications and techniques are
      currently being employed. Studies indicate that the incidence of adverse effects
      from these agents range from less than 1% to almost 30%. Various organizations
      have published guidelines detailing the appropriate protocols and equipment that
      must be present in the emergency department to monitor patients undergoing
      conscious sedation. These recommendations have not been universally implemented,
      and several recent studies suggest that a substantial number of emergency
      departments may have major deficiencies. SUMMARY: The consultant anesthesiologist
      responding to a critical airway may face a variety of challenges, including
      traumatized or soiled airways, patients with cervical spine fractures, and
      patients who have undergone sedation techniques that may have progressed to deep
      and general anesthesia. Anesthesiologists may also face the challenge of
      responding to these emergent situations without all the equipment or adequately
      trained support staff necessary to handle those emergencies safely.

PMID- 17021491
TI  - Interventional neuroradiology.
AB  - PURPOSE OF THE REVIEW: The aim of this review is to give a general overview of
      anesthetic management, technical considerations and specific complications of
      interventional neuroradiology based on the most recent literature. RECENT
      FINDINGS: In more and more services anesthetists become an integrated part in the
      management of patients treated with endovascular neurosurgery. More and more
      centers opt for general anesthesia using less invasive monitoring than with
      common neurosurgery. SUMMARY: Interventional neuroradiology is challenging
      because of the location and the sudden and acutely life-threatening complications
      that may occur.

PMID- 17021493
TI  - Current world literature. Drugs in anaesthesia.

PMID- 17021492
TI  - Advances in office-based anesthesia.
AB  - PURPOSE OF REVIEW: The practice of office-based anesthesia is quickly emerging as
      an important field for the anesthesia provider. The number of procedures being
      done in offices around the country has steadily increased, as has the
      invasiveness of these procedures. This creates new anesthetic considerations. To
      date most training programs have not addressed this area of practice. As
      practitioners enter the field, however, they should have information as to how to
      provide quality care in a location where very often they are completely alone.
      Many of the safety mechanisms we as anesthesia providers take for granted in a
      hospital setting are often not present in a surgical office, and it becomes our
      responsibility to help in establishing standards. RECENT FINDINGS: Some questions
      exist as to the 'safety' of many surgical offices in which anesthesia care is
      provided. Many medical professional societies have begun issuing recommendations
      as to the standards of care that should exist. Different anesthetic techniques
      are also emerging that are appropriate to the office setting. SUMMARY: As office
      based anesthesia continues to mature as a specialty, we the anesthesia providers
      must be proactive in establishing guidelines and recommendations to make the
      practice safe. We should be informed of the rules and regulations that exist in
      our states, and we should provide a voice for the patients who put their faith in
      us.

PMID- 17021494
TI  - Neuronal apoptosis following cerebral ischaemia: pathophysiology and possible
      therapeutic implications.
AB  - PURPOSE OF REVIEW: Neuronal apoptosis following cerebral ischaemia has become an
      issue of extraordinary scientific interest in the past decade. Besides necrosis,
      this highly relevant pathomechanism has been shown to be markedly involved in the
      pathogenesis of delayed postischaemic neuronal damage. As a result, a variety of
      possible neuroprotective strategies and therapeutic options subsequent to
      cerebral ischaemia have emerged. This article provides an overview of the
      pathophysiologic mechanisms underlying delayed neuronal apoptotic degeneration
      after cerebral ischaemia. Based on these facts, selected therapeutic implications
      are discussed in detail. RECENT FINDINGS: Recent findings from experimental
      studies have demonstrated a new therapeutic neuroprotective potential of
      pharmaceutical blockade of death-inducing ligands (e.g. Fas/CD95 ligand),
      enhancement of survival signal transduction with endogenous ligands (e.g.
      erythropoietin) and therapeutically modulating the balance between intracellular
      anti- and proapoptotic Bcl proteins with intriguing molecular techniques after
      cerebral ischaemia. SUMMARY: Neuronal apoptosis is highly relevant in the
      pathophysiology of neurodegenerative disorders, neurotrauma and cerebral
      ischaemia/reperfusion. Within the past few years, a variety of therapeutic
      strategies have emerged based on our increasing knowledge of the pathophysiology
      of apoptosis. Whereas inhibition of single factors in apoptotic cascades (e.g.
      proteases) has produced rather unsatisfying results, new opportunities have
      emerged at the molecular level due to advances in molecular medicine. These
      approaches offer promising opportunities for neuroprotective therapeutic
      strategies subsequent to cerebral ischaemia. It is tempting to speculate that a
      combination ('cocktail') of these antiapoptotic interventions might even increase
      their neuroprotective potential.

PMID- 17021495
TI  - Ischemic preconditioning in the brain.
AB  - PURPOSE OF REVIEW: Brain ischemia is responsible for significant morbidity and
      mortality associated with cardiovascular surgery, and is the end result of
      multiple disease states, including cardiac arrest, stroke, and traumatic brain
      injury. Despite significant resources dedicated to developing neuroprotective
      strategies, little progress has been made in this regard. Neuronal ischemic
      preconditioning is an endogenous neuroprotective strategy that provides sustained
      and robust ischemic tolerance. Identification of the mechanisms responsible for
      mediating the preconditioning response may offer novel therapeutic targets and
      further our understanding of the natural adaptations to brain injury. RECENT
      FINDINGS: Recent research efforts have elucidated many intracellular signaling
      pathways that ultimately lead to ischemic tolerance after a preconditioning
      stimulus. Most of these are associated with glutamate receptor signal
      transduction, the intracellular kinases, and several transcription regulators.
      Microarray analysis has identified several gene families that warrant further
      investigation to identify novel candidates for neuroprotective therapies. These
      include genes involved in synaptic architecture and signal propagation, cell
      cycle and transcription regulators, and mediators of apoptosis such as the heat
      shock proteins and anti-apoptotic mitochondrial proteins. SUMMARY: Neuronal
      ischemic preconditioning is an endogenous mechanism that leads to robust
      neuroprotection from ischemia. Identification of the upstream pathways that
      initiate preconditioning and candidate genes that mediate this phenomenon may
      offer novel therapeutic targets, with applicability to a variety of disease
      states and perioperative complications.

PMID- 17021496
TI  - Regional anaesthesia techniques provide beneficial analgesia in surgical and
      obstetric patients.

PMID- 17021497
TI  - Complications and local anaesthetic toxicity in regional anaesthesia.
AB  - PURPOSE OF REVIEW: Local anaesthetic agents are administered every day in
      clinical practice. These agents are relatively safe when administered in proper
      dosages at appropiate anatomical sites. However, when excessive dosages are
      administered or the incorrect site of administration is used there is a potential
      for toxic reactions. Ropivacaine, a pure S-enantiomer, and levobupivacaine, a
      single isomer of bupivacaine, have been introduced as new long-acting local
      anaesthetic agents with a potentially reduced toxicity compared with bupivacaine.
      The present review deals with recent knowledge about systemically induced local
      anaesthetic toxicity and localized toxicity. RECENT FINDINGS: Studies have
      compared cardiotoxicity directly between ropivacaine and levobupivacaine in
      intracoronary injection in sheep and pigs, in small mammals, and arrhythmias and
      resuscitation in dogs. Direct left coronary arterial infusions of local
      anaesthetics in a conscious sheep model precludes central nervous system actions.
      Intracoronary studies showed similar toxicity for levobupivacaine and
      ropivacaine. When comparing and interpreting in-vivo animal studies of local
      anaesthetic toxicity, species variations, differences in the mode and site of
      local anaesthetic administration, and whether the animal is under the influence
      of anaesthesia must all be considered. Stereoselectivity may play a role in the
      lengthening of the atrioventricular conduction time for bupivacaine. In-vitro
      studies have revealed that intracellular calcium concentrations may contribute to
      myotoxicity. SUMMARY: Current evidence suggests that ropivacaine is slightly less
      toxic than levobupivacaine; however, the difference in potency between the two
      agents is greater. The new local anaesthetic agents can be regarded as 'safer',
      but must not be regarded as safe.

PMID- 17021498
TI  - Neuraxial blocks for anaesthesia and analgesia in children.
AB  - PURPOSE OF REVIEW: The use of regional techniques in paediatric anaesthesia has
      increased dramatically. Our aim is to produce a comprehensive review of the
      recent literature on neuraxial blockade in infants and children, focusing on
      three topics: choice of local anaesthetic and adjunct drugs, technical aspects
      and complications. RECENT FINDINGS: The current literature shows a trend towards
      using the single isomers (levobupivacaine or ropivacaine) rather than racemic
      bupivacaine. In addition, opioids as adjuncts are being challenged by clonidine
      and ketamine, which have more benign side effects. The spread of radiopaque dye
      within the epidural space (which may mimic that of local anaesthetic solutions)
      appears to be highly variable, although distribution is related to the volume
      injected. Recent techniques (e.g. ultrasound or stimulating catheters) have been
      developed to accurately identify the position of epidural catheters. In contrast
      to adults, neuraxial blockade using local anaesthetic solutions is associated
      with stable cardiovascular variables, even in children with congenital heart
      disease. Although the incidence of complications associated with paediatric
      neuraxial blockade is low, the potential risks must always be considered.
      SUMMARY: It is likely that the use of epidural ketamine or clonidine as adjuncts
      to local anaesthetics will grow. Alternatives, such as midazolam, may offer
      advantages in particular circumstances, although rigorous evaluation of the
      safety of these solutions when injected along the neuraxis and the development of
      formulations without preservatives are needed. The use of stimulating caudal
      catheters or ultrasound-guided techniques appears to offer promising options for
      the future to more accurately position catheters.

PMID- 17021499
TI  - Regional anaesthesia in ambulatory surgery.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present recent research into
      the clinical use of regional anaesthesia techniques in ambulatory surgery.
      Further, to put into an ambulatory perspective some of the issues recently
      discussed on the basis and practice of regional anaesthesia in general. RECENT
      FINDINGS: Early discharge with long-acting peripheral nerve blockade seems safe,
      and discharge of patients who have not voided after surgery is possible under
      specified terms. The spinal anaesthesia technique may be improved in terms of
      better and faster recovery characteristics if the dose of local anaesthesia is
      reduced by adding a small dose of opioid. SUMMARY: Loco-regional techniques are
      well suited for ambulatory surgery due to less postoperative nausea and pain and
      possibly less cognitive dysfunction. The different techniques are continuously
      being refined in order to provide fast discharge readiness, while still
      maintaining the benefits.

PMID- 17021500
TI  - Clinically useful adjuvants in regional anaesthesia.
AB  - PURPOSE OF REVIEW: In this review, emphasis is placed on adjuvant drugs that are
      already in clinical use. The list of adjuvants studied during the review period
      includes adrenaline, clonidine, ketamine, neostigmine, nondepolarizing muscle
      relaxants, and nonsteroidal antiinflammatory drugs. Some future aspects are
      considered in a couple of experimental studies on slow-release local anaesthetic
      formulations. RECENT FINDINGS: Adrenaline not only acts as a vasoconstrictor, it
      may also produce analgesia through an alpha2-adrenergic mechanism. Adrenaline may
      facilitate the uptake of the local anaesthetic into nerves. The addition of
      adrenaline to a mixture of ropivacaine and fentanyl clearly improves thoracic
      epidural analgesia. Several recent studies have shown a synergism of clonidine
      with local anaesthetics in various types of blocks, as well as with spinal
      opioids. Bradycardia and hypotension may be associated with the use of clonidine.
      Neostigmine may cause antinociception both in the spinal cord and in peripheral
      nerves. Neostigmine has been found to potentiate the effect of spinal opioids,
      but gastrointestinal side effects are frequent. Biodegradable microcapsules
      containing bupivacaine and dexamethasone have been tested in humans and found to
      produce analgesia for several days (intercostal block). Local inflammatory
      reactions and paraesthesias, however, were observed in 30% of cases. SUMMARY:
      Adrenaline and opioids may be regarded as the best investigated and most
      important adjuvants in regional anaesthesia. Other drugs, such as clonidine and
      neostigmine, may prolong analgesia in various regional anaesthetic techniques,
      but possible side effects may limit their clinical application. Further
      development is needed concerning extra-long acting analgesic formulations.

PMID- 17021501
TI  - Epidural anaesthesia and analgesia for surgery: still going strong?
AB  - PURPOSE OF REVIEW: The discussion on the value of epidural anaesthesia and
      analgesia for surgery is fuelled by current controversies regarding effects on
      postoperative morbidity and mortality, potential benefits for outcome and the
      fear of rare, but catastrophic neurological complications. This review of the
      most recent publications on the topic since April 2002 illustrates some of the
      aspects contributing to the ongoing discussion. RECENT FINDINGS: In contradiction
      to previous meta-analyses, recent trials could not demonstrate significant
      improvements of overall morbidity or mortality by epidural anaesthesia and
      analgesia. However, the technique was shown again to provide superior analgesia
      and a reduction of perioperative stress response and respiratory complications.
      Analysis of the current literature strongly supports that epidural anaesthesia
      and analgesia remains a safe practice with a low rate of severe complications, in
      particular in paediatric surgery. Several developments in equipment, techniques
      and especially drugs have been reported, resulting in improved balanced
      anaesthesia and analgesia and contributing to the safety of this technique.
      SUMMARY: In an era of evidence-based medicine, further meta-analyses and well
      planned large randomized trials have to address the controversial issues of
      epidural anaesthesia and analgesia and postoperative outcome. In the context of a
      more holistic 'rehabilitative' management of the perioperative period, this
      technique might well represent a key factor to improve outcome, reduce hospital
      stay and thereby healthcare costs. Recent innovations and developments in
      techniques and drugs as well as established guidelines should further minimize
      potential errors and harmful complications.

PMID- 17021502
TI  - Peripheral nerve blocks for anaesthesia and postoperative analgesia.
AB  - PURPOSE OF REVIEW: Perioperative analgesia is a major concern for the patient and
      for the anesthesiologist, whose task is to avoid pain and all related
      complications on immediate outcome and healing. Regional anesthesia, alone or
      combined with general anesthesia, is becoming a preferred technique in a variety
      of surgical procedures. There is increasing interest in peripheral nerve blocks,
      single or continuous, mainly for perioperative treatment of unilateral surgery.
      Specificity of analgesic area combined with decreased complications, including
      spinal or epidural hematoma, urinary retention, or hemodynamic alterations, are
      advantages of the peripheral nerve block over more central neural blocks. RECENT
      FINDINGS: Insertion of catheters near neural plexuses or in the vicinity of
      single nerves are being continuously developed and improved. The appearance of
      new techniques and devices is increasing. Percutaneous electrode guidance,
      ultrasonographic localization of neural structures, and the use of stimulating
      catheters represent the newest advances in this area. Use of enantiomeric local
      anesthetic drugs permits a safer and wider range of postoperative treatment,
      which includes continuous analgesia administered in the patient's home. Use of
      patient-controlled analgesia, through electronic or elastomeric pumps, is
      recommended for postoperative pain control. Peripheral nerve block is the
      standard for anesthesia or analgesia in ambulatory surgery. Complications of the
      technique have been examined in large clinical studies which have recently been
      published. Results of such studies highlight the effectiveness and safety of
      peripheral blocks. These results have given new strength to arguments for
      regional anesthesia and analgesia and led to the increase in popularity of
      regional techniques. The articles considered below have, in summary, the main
      purpose of enhancing safety, as well as dissemination and education regarding
      regional anesthetic techniques. SUMMARY: Possibilities afforded by the use of
      peripheral nerve blocks mainly consist of prolonged analgesia, selective area of
      action, and fewer collateral effects when compared with general anesthesia or
      more central neural blockade. Introduction of new devices and new techniques are
      increasing, as evidenced by the large number of studies which have appeared in
      the literature during the past year.

PMID- 17021503
TI  - Obstetric spinal analgesia and anesthesia.
AB  - PURPOSE OF REVIEW: The present overview will try to summarize the most important
      recent studies performed on spinal analgesia for labor pain treatment and spinal
      anesthesia for Cesarean section. RECENT FINDINGS: Attention is focused on
      pharmacological and technical topics. The interest in demonstrating the benefits
      of the new local anesthetics over bupivacaine seems to have faded. The search for
      other adjuvant drugs continues, but it is not clear whether opioids need to be
      replaced or combined with other adjuvants. A large number of studies are still
      dealing with vasopressor treatment of hypotension during Cesarean section. There
      is growing evidence that ephedrine is no longer the vasopressor drug of choice
      and that phenylephrine should take its place. In technical studies, discussion on
      combined spinal-epidural versus epidural continues, but it remains difficult to
      provide definitive evidence that combined spinal-epidural is more advantageous.
      Also the increased possibility of ambulation has not resulted in benefits other
      than enhanced maternal satisfaction. Finally, spinal techniques seem to have lost
      their reputation as being a dangerous choice in patients with severe preeclampsia
      or cardiac disease. SUMMARY: The new local anesthetics have established their
      position in obstetric regional anesthesia, but it remains difficult to
      demonstrate a superior outcome as compared with bupivacaine. The same is true for
      combined spinal-epidural and ambulation. Phenylephrine seems to have become the
      vasopressor of choice in the treatment of hypotension following spinal
      anesthesia. A more appropriate treatment of hypotension combined with a low-dose
      technique may enhance the safety of spinal anesthesia in preeclamptic patients or
      cases of severe cardiac disease.

PMID- 17021504
TI  - Is immunomodulation by opioid drugs of clinical relevance?
AB  - PURPOSE OF REVIEW: There has been a growing interest in elucidating the immune
      consequences of opioid administration for the management of pain. Several studies
      in vitro and in vivo have demonstrated an immunomodulating effect of opioids. The
      neuro-endocrine interactions observed after opioid application contribute to this
      effect as well as direct alterations of immune effector cells. Opioid-induced
      immunomodulation is mediated by opioid receptors found on immunocytes and in the
      central nervous system. This review will elucidate the molecular mechanisms of
      central and peripheral immunomodulation by opioids with special emphasis on the
      clinical significance of these findings. RECENT FINDINGS: Recent research has
      focused on the cellular signaling cascades associated with opioid receptor
      activation. The crosstalk between chemokine and opioid receptors on leukocytes
      has opened new insights into the molecular mechanisms involved in opioid-induced
      immunomodulation. Heterologous desensitization and phosphorylation of chemokine
      receptors by opioids may not only mediate the immunosuppressive effects of
      opioids but may also modulate the perception of pain. SUMMARY: Although
      immunomodulating effects of opioids are well established, a final statement
      regarding the clinical relevance cannot be made, since the existing clinical and
      experimental data are preliminary and inconclusive. Therefore, further clinical
      studies are mandatory to elucidate the influence of opioid treatment on immune
      regulation in different clinical settings. Further investigations may help to
      provide sufficient analgesia by application of opioids, as well as assessing the
      advantages and disadvantages on immune function.

PMID- 17021505
TI  - New insights into placebo analgesia.
AB  - PURPOSE OF REVIEW: The placebo effect is a widespread phenomenon in medicine,
      both in clinical trials and in routine medical practice. Most of our knowledge
      about the underlying psychological and physiological mechanisms comes from the
      study of placebo analgesia. RECENT FINDINGS: When the correct methodological
      approach is used, striking placebo effects can be detected and these can be
      mediated by conscious anticipatory processes or unconscious conditioning
      mechanisms. However, it should be stressed that many improvements observed after
      the administration of a placebo are not real placebo effects, but different
      phenomena such as spontaneous remission, regression to the mean and symptom
      detection ambiguity. Both neuropharmacological studies and brain imaging
      investigations show that placebo analgesia is mediated by endogenous opioids.
      Moreover, we also know that during placebo analgesia other systems change their
      functions, like the respiratory centres and the cardiovascular system. The
      placebo effect has also been approached from a different perspective by
      administering analgesics covertly. The results show that hidden medical
      treatments are less effective than open ones. SUMMARY: The understanding of the
      placebo effect may lead to better design of clinical trials and better medical
      practice. For example, it can be used in therapeutic protocols aimed at reducing
      drug intake.

PMID- 17021506
TI  - Novel molecular targets in pain control.
AB  - PURPOSE OF REVIEW: The complexity of pain processing in clinical pain conditions
      and in animal models has revealed many time-related changes and an abundance of
      molecular drug targets. There continues to be insecurity, however, about new
      target validation in clinical pain and thus most analgesia development is of high
      risk for evolving new pain therapies. The present review highlights a number of
      molecular targets being pursued for pain control. RECENT FINDINGS: Many pain
      targets are critically dependent on the pain model/lesion type. Neural and glial
      plasticity, ranging from changes in molecular expression and receptor
      phosphorylation to profound morphological reorganization, has been described
      under these conditions. Pain modulation has been shown to involve all major
      families of regulatory proteins such as the G-protein coupled receptors, ion
      channels, regulatory enzymes, neurotrophins, and kinases, offering an abundance
      of targets and therapeutic opportunities for symptomatic pain relief. SUMMARY:
      Many molecular targets have been highlighted with some being the focus of current
      analgesia research. Some of these (e.g. vanilloid receptor 1, cannabinoid
      receptor 1, sodium channel NaV 1.8) have been evaluated in animal studies and in
      preliminary clinical studies, but others are highly novel and riskier analgesia
      pain targets (e.g. metabotropic glutamate receptors, sensory neurone specific
      receptors, kinase inhibitors).

PMID- 17021507
TI  - Pro-algesic versus analgesic actions of immune cells.
AB  - PURPOSE OF REVIEW: When tissue is destroyed, pain arises. Tissue destruction is
      associated with an inflammatory reaction. This leads to activation of
      nociceptors. The following review will concentrate on pro-algesic and analgesic
      mediators, which arise from immune cells or resident cells in the periphery or
      the circulation during inflammation. RECENT FINDINGS: In early inflammation
      endogenous hyperalgesic mediators are produced, including cytokines, chemokines,
      nerve growth factor as well as bradykinin, prostaglandins and ATP.
      Simultaneously, analgesic mediators are secreted: opioid peptides, somatostatin,
      endocannabinoids and certain cytokines. Inflammation increases the expression of
      peripheral opioid receptors on sensory nerve terminals and enhances their signal
      transduction, as well as the amount of opioid peptides in infiltrating immune
      cells. Interference with the recruitment of opioid-containing immune cells into
      inflamed tissue by blockade of adhesion molecules or by intrathecal morphine
      injection reduces endogenous analgesia. SUMMARY: Inflammatory pain is the result
      of the interplay between pro-algesic and analgesic mediators. To avoid central
      side effects, future analgesic therapy should be targeted at either selectively
      blocking novel pro-algesic mediators or at enhancing endogenous peripheral
      analgesic effects.

PMID- 17021508
TI  - New models for visceral pain.
AB  - PURPOSE OF REVIEW: After the initial use of unspecific stimuli, scientists have
      recently put a lot of effort into the development of new visceral pain models.
      These models will help to study physiological and pharmacological questions
      closely related to clinically treated visceral pain. The aim of this review is to
      provide an overview of the new models published most recently and encourage
      further studies in this field. RECENT FINDINGS: Four rodent and three human
      models have been introduced. Each of these models addresses specific types of
      visceral pain, related to the urogenital tract (n=3), to the gastrointestinal
      tract (n=3), and to visceral organs (n=1). Mechanical distension as a brief
      stimulus was used mainly, but chemical stimuli resulting in intermediate to
      prolonged duration of pain were also investigated. SUMMARY: Developments in the
      scientific visceral pain field are encouraging. Growing interest in studying
      aetiology, physiology and pharmacology of visceral pain proves the clinical
      importance of this pain entity. However, these new models need further
      evaluation. Future studies will show which of these new models will become a
      standard scientific tool.

PMID- 17021509
TI  - Peripherally restricted opioid drugs: advances and retreats.
AB  - PURPOSE OF REVIEW: The aim of this article is to familiarize anesthesiologists
      with recent research investigating peripheral opioid analgesia. The review
      focuses on studies of peripheral receptor distribution in humans and clinical
      data that support the hypothesis of peripheral analgesia that have been published
      over the past 2 years. RECENT FINDINGS: Recent anatomical studies using human
      tissue have detected the presence of mu-opioid receptors in epidermal and dermal
      layers of normal skin, although expression was not altered in certain dermal
      clinical conditions. Nerve fibers of human dental pulp also contained detectable
      mu-opioid receptors. A survey of the clinical literature on peripherally mediated
      mu analgesia suggests that under conditions of inflammation, the onset of
      analgesia is typically delayed, but once initiated, is of long duration. A
      peripherally selective kappa agonist was efficacious in relieving the pain
      associated with chronic pancreatitis. SUMMARY: Peripheral analgesia mediated
      through the mu-opioid receptor has been demonstrated in a variety of clinical
      settings, with the preponderance of data generated with arthroscopic procedures.
      Receptor localization studies using human tissue have corroborated the presence
      of the mu-opioid receptor in the periphery. Future research is needed to
      investigate the clinical utility of kappa and delta-opioid receptor agonists in
      the peripheral setting.

PMID- 17021510
TI  - Experimental gene therapy of chronic pain.
AB  - PURPOSE OF REVIEW: During the past few years novel gene-based approaches emerged
      attempting to treat chronic pain experimentally in animal models. This review
      will discuss some of the most recent developments in this area with special
      emphasis on vector-mediated targeted transfer of DNA at the spinal level. RECENT
      FINDINGS: Local overexpression of precursors of opioid peptides, mainly at the
      spinal level, induces antihyperalgesic effects in various animal models of
      persistent pain. Different techniques enabling the in vivo transfer of these
      precursors have been described. Virus-derived vectors appear as potent systems,
      providing targeted and sustained overproduction of opioid peptides.
      Interestingly, overexpression of proenkephalin A in primary sensory neurones
      induced antinociceptive effects in persistent pain of inflammatory, neuropathic
      and cancerous origins. Targeted overproduction of many other proteins may be
      relevant to the relief of ongoing pain. For instance, local overproduction of
      brain derived neurotrophic factor in the spinal cord has been reported to treat
      neuropathic pain induced by chronic constrictive injury of the sciatic nerve.
      SUMMARY: Gene-based techniques may contribute to the search for a better
      management of chronic pain. In this respect, tempting data were obtained in
      animal models of persistent pain using viral vector-mediated overproduction of
      opioid peptides and neurotrophins. Gene-based protocols targeting some molecules
      involved in pain induction and perpetuation also raise the interesting
      possibility of blocking the development of chronic pain, rather than relieving
      it. Apart from the 'gene therapy' of chronic pain, the clinical application of
      which still remains to be established, these techniques might help in evaluating
      the potential interest of some recently identified molecules involved in pain
      transduction mechanisms or sensory nerve sensitization. They might finally lead
      to the development of new classical pharmacological tools.

PMID- 17021511
TI  - Current world literature. Neuroanaesthesia.

PMID- 17021512
TI  - Peripheral nerve block for ambulatory surgery and postoperative analgesia.
AB  - PURPOSE OF REVIEW: With this article we intend to increase the awareness of the
      efficiency and efficacy of peripheral nerve block as a treatment option for
      outpatient surgical anesthesia and postoperative home-based analgesia. RECENT
      FINDINGS: Current investigations have demonstrated that peripheral nerve block is
      associated with a superior outcome (reduced pain, nausea and vomiting) and more
      efficient patient turnover than general anesthesia. Continuous peripheral nerve
      block and patient controlled peripheral nerve block lead to further improvement
      in postoperative analgesia and patient satisfaction. SUMMARY: The recent advances
      and techniques described indicate that peripheral nerve block is both a valid and
      frequently a preferred option for ambulatory surgery.

PMID- 17021513
TI  - Management of postoperative vomiting in pediatric patients.
AB  - PURPOSE OF REVIEW: Postoperative vomiting remains a common complication of
      general anesthesia and occurs more frequently in children than adults.
      Prophylactic antiemetics have limited efficacy and have a potential for side
      effects. The new 5 HT3 antagonists are effective but expensive, while the older
      less expensive drugs such as droperidol have come under disrepute because of the
      potential for serious, life-threatening, cardiac arrhythmias. This review
      examines the literature to aid practicing anesthesiologists in the choice of
      patient who will benefit from prophylactic antiemetics. RECENT FINDINGS: In this
      review we discuss the factors associated with postoperative vomiting that are and
      are not under the control of the anesthesiologist. The Consensus Panel
      recommendations for reducing the risks of postoperative vomiting and for the
      rational use of prophylactic antiemetics in selected cases are reviewed. The
      controversy over the 'black box warning' on the use of droperidol is discussed.
      Finally, the evidence supports the importance of choosing a drug from another
      class for rescue therapy when prophylaxis with one drug has failed. SUMMARY:
      Anesthesiologists should practice evidence-based medicine in reducing the common
      anesthetic complication of postoperative vomiting by an individualized approach
      that balances the choice of drugs with the expected risk of postoperative
      vomiting for cost-effective management.

PMID- 17021515
TI  - Reducing medical error: recommendations from residents - they 'say the darndest
      things'.

PMID- 17021514
TI  - Anesthesiologists on ambulances: where do we stand?
AB  - PURPOSE OF REVIEW: This manuscript provides a critical review of the literature
      regarding the staffing of emergency medical services, with particular emphasis on
      anesthesiologists. RECENT FINDINGS: Significant anesthesiology contributions to
      prehospital care include introduction of new airway management tools and improved
      physiological monitoring. Contributions to quality of care include patient
      benefit in terms of life years gained and a specific reduction in mortality from
      acute myocardial infarction. Intuitive concepts regarding the advantage of
      anesthesiologists in intubation mishaps and management of the failed airway have
      yet to be proven. Personnel limitations may be regional, necessitating local
      evaluation of anesthesiologist availability to staff ambulances. Since a major
      part of cost-effectiveness research is performed in the US where only paramedics
      staff ambulances, insufficient data exist regarding the financial implications of
      such practice. Burnout may be an important factor for deciding whether
      anesthesiologists should work in the operating room or ambulances or on an
      alternate basis. SUMMARY: Further research should be performed to evaluate the
      clinical and financial implications of staffing ambulances with anesthesiologists
      or other physicians. Randomized controlled studies using standardized intubation
      techniques are necessary to examine whether prehospital airway management is
      improved when delivered by anesthesiologists.

PMID- 17021516
TI  - Professionalism: identifying current themes.
AB  - PURPOSE OF REVIEW: This review analyzes the literature on medical professionalism
      in order to inform further study, educational activity, and reflective practice
      for all phases of a physician's professional development from medical school
      through practice. RECENT FINDINGS: Several themes emerged from an analysis of the
      writing about medical professionalism during the past year. A number of authors
      attempted to identify concrete behaviors associated with attributes and
      characteristics used to define professionalism. These behaviors in turn became
      the focus of teaching and assessment activities primarily conducted with medical
      students and residents. Educators who attempted to assess professionalism
      achieved some modest success in reporting valid and reliable results of their
      efforts. Each of these activities points to a systemic component of
      professionalism that includes five broad categories of relationships in which
      physicians engage. All five categories are important to understanding and acting
      on the values and attitudes required by professionalism in medicine. SUMMARY:
      Competence to practice medicine includes the ability of physicians to demonstrate
      professionalism in all the relationships in which they engage. The attributes and
      characteristics used to define professionalism contribute to recognizing the
      behaviors that should be apparent not only in the physician-to-patient
      relationship which is at its core, but also in relationships with other
      physicians, colleagues in the health care system, society, and oneself. All these
      relationships must be appropriately aligned with the values and attitudes that
      form a collective understanding of professionalism that has emerged within the
      profession.

PMID- 17021517
TI  - Resident work hours.
AB  - PURPOSE OF REVIEW: The Accreditation Council for Graduate Medical Education has
      mandated new requirements for work hours for all US resident physicians that
      became effective in July 2003. Member countries of the European Union are also
      implementing a reduction in work hours for trainee physicians as per the European
      Work Time Directives. The following review provides a summary of the basis of
      limiting work hours for residents, steps taken towards limiting the working hours
      for resident doctors, and implications to residents, institutions, and states.
      RECENT FINDINGS: Reduction of work hours for physicians in training is a much
      awaited and necessary change. Though the framework for such a reduction is in
      place in most countries, implementation of the policies has been slow thus far,
      mainly due to financial and manpower constraints. Setting of deadlines for
      compliance and legislation to penalize the defaulting institutions and programs
      may help to put the recommendations on work hours into practice. SUMMARY: Long
      work hours contribute to stress, fatigue, and mood changes in trainee physicians
      that are potentially deleterious to the physician and patients. Recommendations
      have been made across the globe to reduce resident doctor work hours and
      legislation is in place to monitor institutional compliance with these
      recommendations. Once these regulations are complied with, follow-up studies will
      be needed to evaluate their effects on physician well-being and patient care.

PMID- 17021518
TI  - Scavenging in the operating room.
AB  - PURPOSE OF REVIEW: The use of inhalation general anesthetic gases has led to
      contamination of the operating room environment. Chronic exposure to these agents
      has been associated with a number of adverse health effects. Controversy remains
      with regard to these health effects, and whether further reducing the level of
      operating room contamination should be a high priority. Current methods are
      outlined by which anesthetic waste gases contaminate and are removed from the
      operating room. These controversies are explored in the light of recent research.
      RECENT FINDINGS: Recent work employing genotoxicity studies suggests that
      National Institute for Occupational Safety and Health recommendations may be
      appropriate to protect healthcare workers. New developments over the past year
      include the suggestion of employing devices such as the Anesthetic Scavenging
      Hood (ASH), SiBI tube connector and mask stopper. The use of these devices, in
      concert with efficient anesthesia machine scavenging, may further reduce
      operating room contamination. SUMMARY: The National Institute for Occupational
      Safety and Health calls for lower levels of exposure when compared with those
      found in European standards. It may be appropriate for European guidelines to be
      re-addressed; however, more conclusive studies need to be undertaken to identify
      the precise effects of these agents at a given exposure level. It may also be
      appropriate to expand the arena of monitoring and scavenging to all areas where
      inhalation anesthetics are used or emitted, such as in the post-anesthesia care
      unit and research laboratory settings.

PMID- 17021519
TI  - Operating room utilization: information management systems.
AB  - PURPOSE OF REVIEW: Advances during the past year in operational decision making
      using information management systems data have been predominantly in better
      understanding of how to allocate operating room time based on operating room
      efficiency, not just operating room utilization. RECENT FINDINGS: Each quarter,
      operating room allocations based on maximizing operating room efficiency can be
      calculated with 6-10 months of data. Analysis can be performed using operating
      room or anesthesia information management system data. Uncertainty in knowing the
      operating rooms in which cases were performed (i.e. in knowing turnover times)
      has little effect on operating room allocations or efficiency. It is important,
      however, that when a service has filled its allocated operating room time and has
      a new case to schedule, the case be scheduled into the operating room time of
      another service. The service whose operating room time is released can be the
      service with the largest difference between allocated and scheduled operating
      room time at the time when the new case is scheduled. If optimal operating room
      allocations and case scheduling based on maximizing operating room efficiency are
      not implemented, the resulting increase in anesthesia group labor costs can be
      used in negotiations as a statistically sound estimate for the increased labor
      cost to the group. SUMMARY: During the last couple of years there has been
      continual advancement in our understanding of how to analyze operating room
      information system data based on operating room efficiency. Work has expanded
      from operating room allocations to case scheduling, releasing allocated operating
      room time, and addressing implementation challenges including poor data quality
      or lack of interest in change.

PMID- 17021520
TI  - Current world literature. Ambulatory anaesthesia.

PMID- 17021522
TI  - Double-lumen tube position should be confirmed by fiberoptic bronchoscopy.
AB  - PURPOSE OF REVIEW: This review is part of Pro and Contra use of fiberoptic
      bronchoscopy to confirm the position of a double lumen tube. The purpose of this
      review is to highlight the circumstances where fiberoptic bronchoscopy should be
      used in conjunction with lung separation, right sided double-lumen tube
      positioning, and to identify fine malposition for generally missed by clinical
      signs. RECENT FINDINGS: Until several years ago, confirmation of a double-lumen
      tube (DLT) position was limited to inspection and auscultation. Fiberoptic
      bronchoscopes were usually only available in the bronchoscope suite for the
      exclusive use of the pulmonary personnel. Today, in most institutions, fiberoptic
      bronchoscopes of different diameters are available in the operating room for use
      by the anesthesia personnel. SUMMARY: Advances in technology and improved quality
      of the endoscopes image make the technique easy to use with a relatively simple
      learning curve. In fact, fiberoptic workshops, thoracic workshops and difficult
      airway workshops are offered in nearly all important anesthesia meetings.

PMID- 17021523
TI  - Fiberoptic bronchoscopy need not be a routine part of double-lumen tube
      placement.
AB  - PURPOSE OF REVIEW: The debate continues as to whether a fiberoptic bronchoscope
      must be used to position a double-lumen tube. This review supports the argument
      that although bronchoscopy is extremely helpful, it is not always needed for the
      routine placement of left double-lumen tubes. RECENT FINDINGS: Several recent
      clinical reports have demonstrated that an experienced anesthesiologist can
      safely and consistently position double-lumen tubes without bronchoscopic
      assistance. In order to do so several important factors must be considered. These
      include the appropriate choice of tube (left or right), size of tube, and
      endpoint for the depth of insertion. SUMMARY: Although bronchoscopy is useful, no
      double-lumen tube positioning method is fail-safe. The choice of which approach
      to use, 'blind' versus fiberoptic bronchoscope-assisted, is influenced by many
      factors. Operator experience with any method increases the likelihood of success.
      A fiberoptic bronchoscope is not always needed for left double-lumen tube
      placement.

PMID- 17021524
TI  - Gene therapy in heart and lung disease.
AB  - PURPOSE OF REVIEW: Gene therapy utilizes viral and non-viral vectors to transfer
      genetic material into a host in the hope of treating disease. This article will
      review the potential applications of gene therapy in the treatment of cardiac and
      pulmonary diseases. RECENT FINDINGS: The results from several phase I and II
      clinical trials have recently been published. In patients with ischemic heart
      disease, evidence of coronary revascularization has been observed after the
      delivery of angiogenic factors. Several trials have demonstrated a reduction in
      anginal symptoms, increases in exercise tolerance, and objective improvements in
      myocardial perfusion. Evidence of the transfer of therapeutic genes has been
      observed in human trials of inherited pulmonary diseases. Unfortunately, there
      has been little evidence of clinical efficacy in these studies. A variety of gene
      therapy strategies are being explored in the treatment of thoracic malignancies.
      Partial antitumor responses have occurred in some of the subjects enrolled in
      these studies. SUMMARY: Significant progress has been made in the field of gene
      therapy in the past decade. Data from these early animal and human clinical
      trials will provide important information to guide future studies.

PMID- 17021526
TI  - New perspectives for an old cure: a glucose-insulin-potassium revival in cardiac
      surgery?

PMID- 17021525
TI  - Obesity, sleep apnea, the airway and anesthesia.
AB  - PURPOSE OF REVIEW: Recent articles indicate that at the present time disastrous
      respiratory outcomes during the perioperative management of patients with
      obstructive sleep apnea are a major problem for the anesthesia community. RECENT
      FINDINGS: A recent review of the literature indicates that disastrous respiratory
      outcomes are due to intubation failure, respiratory obstruction soon after
      extubation, and respiratory arrest after narcotic and sedative medication. In
      obese patients, the basic problem is deposition of adipose tissue in the pharynx.
      The excessive adipose tissue in the pharynx causes both the intubation and
      respiratory obstruction soon after extubation problems. Finally, opioid
      administration in the postoperative period adds the insults of depression of
      ventilation in general and depression of arousal to obstructed breathing during
      the sleep in specific, which creates in turn, the potential for the arrest of
      spontaneous ventilation, especially in unmonitored patients. SUMMARY: Adult obese
      patients with suspected or sleep test confirmed obstructive sleep apnea present a
      formidable challenge throughout the perioperative period. Tracheal intubation and
      extubation decisions in obese patients with either a presumptive or sleep study
      diagnosis of obstructive sleep apnea must be made within the context that there
      may be excess tissue in the pharynx. If opioids are used in the extubated
      postoperative obese patient with sleep apnea, then one must seriously consider
      the need for continuous visual and electronic monitoring. Institutional and
      national society guidelines on these matters are badly needed.

PMID- 17021527
TI  - New strategies to control the inflammatory response in cardiac surgery.
AB  - PURPOSE OF REVIEW: To present and interpret data from recent clinical studies
      (July 2002-August 2003) of strategies to control the inflammatory response after
      cardiac surgery. RECENT FINDINGS: Off-pump coronary artery bypass techniques,
      which avoid the need for extracorporeal circulation, attenuate the inflammatory
      response and appear to confer clinical benefit. Concerns regarding the quality of
      the revascularization after off-pump coronary artery bypass appear to have been
      allayed. At present, ventricular assist devices do not enhance the efficacy of
      off-pump coronary artery bypass. In patients undergoing cardiopulmonary bypass,
      heparin-coated circuits, hypothermic pulmonary perfusion, normoxic reperfusion
      after aortic unclamping, and modified ultrafiltration hold promise. Strategies to
      maintain perioperative haemodynamic stability, such as enoximone therapy, may be
      beneficial, particularly in elderly patients. Aprotinin may have important
      beneficial anti-inflammatory actions in higher-risk adult and paediatric
      patients. The therapeutic potential of corticosteroids, particularly when
      administered in multiple dosages is increasingly clear. Direct anti-mediator
      therapies that focus upon key effector molecules and pathways of the inflammatory
      response offer future therapeutic options. SUMMARY: The potential for strategies
      that inhibit the inflammatory response to improve outcome after cardiac surgery
      is clear. Large-scale multicentre trials investigating the most promising
      strategies, including off-pump coronary artery bypass, heparin-coated circuits,
      and perioperative corticosteroid and aprotinin therapy, are urgently needed.
      These trials need to be restricted to the high-risk patient groups most likely to
      experience benefit. In the interim, the optimal strategy to minimize the
      inflammatory response to cardiac surgery will remain elusive.

PMID- 17021528
TI  - Clinical utility of biomarkers in myocardial injury.
AB  - PURPOSE OF REVIEW: This review will focus on recent developments in biomarkers of
      myocardial injury. We will discuss the clinical utility of cardiac-specific
      troponin in the post-operative setting and highlight some of the most promising
      new biomarkers under development. RECENT FINDINGS: Troponin I and T, measured in
      the post-operative setting, have been recently shown to have strong short- and
      long-term prognostic information in cardiac and vascular surgery patients. This
      ability of troponins to risk stratify post-operative patients occurs independent
      of clinical factors and other biomarkers. Additionally, brain natriuretic peptide
      has garnered significant interest as a biomarker of neurohormonal activation and
      appears to yield independent prognostic information from troponins. Recent
      studies have introduced two new biomarkers, soluble CD40 ligand and ischemia
      modified albumin, which may aid in both diagnostic and prognostic decision
      making. SUMMARY: The current data strongly supports the use of troponin I and T
      in post-operative non-cardiac and cardiac surgical patients to assist in
      identifying those patients at high risk for short- and long-term complications.
      Several promising new biomarkers are currently under development but further
      studies are warranted to define their role in the post-operative setting.

PMID- 17021529
TI  - Cardioprotection with volatile anesthetics: clinical relevance.
AB  - PURPOSE OF REVIEW: Increasing experimental evidence is indicating that volatile
      anesthetic agents may exert direct cardioprotective effects. They have been shown
      to directly precondition or indirectly enhance ischemic preconditioning. This
      results in protection against reversible and irreversible ischemic myocardial
      damage. In addition, volatile anesthetics also decrease the extent of the
      reperfusion injury when administered only during the reperfusion period. The
      implementation of these properties during clinical anesthesia might provide an
      additional tool in the treatment and prevention of ischemic cardiac dysfunction
      in the perioperative period. RECENT FINDINGS: In clinical practice, these effects
      should be associated with improved cardiac function, ultimately resulting in a
      better outcome in patients with coronary artery disease. This potential
      application of anesthetic agents has only recently been explored and its
      applicability in clinical practice is the subject of ongoing research. SUMMARY:
      This review will summarize the current knowledge in this field and also discuss
      the potential mechanisms involved in cardioprotection by anesthetic agents.

PMID- 17021530
TI  - Atrial fibrillation and cardiac surgery.
AB  - PURPOSE OF REVIEW: To discuss the pathophysiology, risk factors, and treatments
      for atrial fibrillation occurring after cardiac surgery. RECENT FINDINGS: Atrial
      fibrillation occurs frequently after cardiac surgery and it may lead to patient
      morbidity. Many variables have been suggested to be associated with this
      arrhythmia, but only advanced patient age can consistently identify risk for this
      complication. Immediate electrical cardioversion is indicated when the arrhythmia
      leads to hemodynamic instability or myocardial ischemia. Otherwise treatment is
      aimed at heart rate control, elective cardioversion with drugs or electrical
      means, and anticoagulation when the arrhythmia persists. Multiple investigations
      have evaluated methods for preventing postoperative atrial fibrillation, but only
      beta-adrenergic receptor blocking drugs have been consistently shown to be
      effective, and then not in all patients. Surgical treatments are increasingly
      being considered as a therapeutic means for ameliorating chronic atrial
      fibrillation. The use of these procedures has been simplified with the
      development of devices that can generate linear scars in the atrium and around
      the pulmonary vein orifices. These simplifications will allow for broader
      application of these techniques to patients undergoing other cardiac surgery
      (e.g. mitral valvular surgery). SUMMARY: Atrial fibrillation is one of the most
      common complications of cardiac surgery. There are three major aims for treating
      atrial fibrillation: conversion to sinus rhythm, heart rate control, and
      anticoagulation. Only beta-blockers can be recommended for prophylaxis against
      postoperative atrial fibrillation. Further refinements in surgical treatments for
      atrial fibrillation may allow for wider applications of this therapy with lower
      rates of complications.

PMID- 17021531
TI  - Anticoagulation of patients with heparin-induced thrombocytopenia in cardiac
      surgery.
AB  - PURPOSE OF REVIEW: The hazards of heparin-induced thrombocytopenia in patients
      undergoing cardiac surgery are increasingly being appreciated. Decision-making in
      favor of an alternative anticoagulation strategy in the complex perioperative
      setting of cardiac surgery, however, remains a predicament. The aim of this
      review is to provide an overview of the current strategies for the treatment of
      patients with heparin-induced thrombocytopenia in this setting. RECENT FINDINGS:
      With the introduction of the direct thrombin inhibitors, approved alternative
      anticoagulants for pre- and postoperative thrombosis prophylaxis are available.
      Regarding intraoperative anticoagulation, convincing evidence suggests that, if
      no heparin-induced thrombocytopenia antibodies are present, anticoagulation
      during cardiopulmonary bypass can be safely performed with unfractionated
      heparins when the administration of heparin is restricted to the short period of
      cardiopulmonary bypass. If antibodies are present and surgery cannot be
      postponed, however, an alternative anticoagulation strategy must be employed. All
      the currently used strategies, such as administration of direct thrombin
      inhibitors or the combination of unfractionated heparin with antiplatelet agents,
      involve three problems: (1) strategies are 'off-label' in this indication; (2) no
      antidote is available, implying the potential risk of severe hemorrhagic
      complications; and (3) assays for point-of-care monitoring are not approved or
      available. SUMMARY: If possible, surgery should be delayed until antibody titers
      are negative. However, if antibodies are present and surgery cannot be postponed,
      in a synoptic approach, the anticoagulation protocol and the surgical strategy
      must be adjusted to the condition of the patient and the experience of the center
      in order to reduce the risk of these 'off-label' strategies.

PMID- 17021533
TI  - Current world literature.

PMID- 17021532
TI  - Current status of cardiac resynchronization therapy.
AB  - PURPOSE OF REVIEW: Cardiac resynchronization therapy with biventricular pacing
      has rapidly emerged as an indispensable treatment option in patients with
      moderate-to-advanced heart failure and left bundle branch block. New findings on
      the pathophysiology of cardiac resynchronization therapy and its clinical effects
      are reviewed. RECENT FINDINGS: Several randomized trials have evaluated the
      effects of cardiac resynchronization therapy on cardiac haemodynamics and
      clinical parameters in selected heart failure patients with left bundle branch
      block. The effects of cardiac resynchronization therapy on mechanical synchrony
      have been evaluated by different imaging modalities, such as echocardiography and
      radionuclide angiography. Cardiac resynchronization therapy leads to improved
      haemodynamics at a diminished energy cost, and improves functional mitral
      regurgitation. This haemodynamic improvement is associated with a significantly
      better quality of life, improved exercise capacity, and less frequent
      hospitalization. Recent preliminary data suggest a positive effect on cardiac
      mortality. However, approximately a third of implanted patients do not benefit
      from cardiac resynchronization therapy, and therefore additional criteria for the
      identification of mechanical dyssynchrony are needed to identify those patients
      who will respond before implantation. SUMMARY: Many randomized trials have
      confirmed the benefits of cardiac resynchronization therapy in selected heart
      failure patients. The successful resynchronization of the ventricular activation
      contraction sequence is the major determinant of acute haemodynamic and long-term
      clinical improvement. The diagnostic sensitivity and specificity of the non
      invasive identification of mechanical dyssynchrony may be improved by
      echocardiography, but further research is needed to identify the optimal strategy
      for patient identification.

PMID- 17021535
TI  - Differential gene expression: a (new) topic in the intensive care unit.

PMID- 17021536
TI  - Sepsis in 2003: are we still in the middle of nowhere?
AB  - PURPOSE OF REVIEW: Although enthusiasm of intensivists has been raised during the
      last 2-3 years due to several successful clinical trials, severe sepsis and
      septic shock still have an increasing incidence with more or less unchanged
      mortality. Within the last 12 months, the progress in sepsis research covering
      definitions, epidemiology, pathophysiology, diagnosis, standard and adjunctive
      therapy, as well as experimental approaches is encouraging. In this review, state
      of-the-art publications of 2003 are presented to elucidate the possible impact on
      clinical routine. RECENT FINDINGS: The rationale for using a new definition based
      on the PIRO system has been widely acknowledged, although it is not yet
      applicable in clinical practice. This includes genomic information for
      stratifying subgroups of patients, and a broader field of laboratory diagnostics
      due to clinical studies and basic research on the cellular mechanisms of
      inflammation and organ dysfunction. Early diagnosis is important for a fast
      implementation of specific therapies, and it has been confirmed that the time
      until the start of therapy has an impact on patient outcome. Thorough data
      analysis of successful trials with activated protein C has revealed encouraging
      details on long-term outcome and subgroup effects. Together with new findings on
      low-dose hydrocortisone, this stresses the relevance of adjunctive therapy in
      severe sepsis and septic shock. SUMMARY: Scientific progress in areas of sepsis
      has been continuing throughout 2003, although the challenges are still enormous.
      The identification of more specific markers and new therapeutic approaches will
      hopefully improve the diagnosis, monitoring of therapy, and outcome in the septic
      patient.

PMID- 17021537
TI  - Monitoring oxygen transport and tissue oxygenation.
AB  - PURPOSE OF REVIEW: To review recent publications in the field of oxygen delivery
      and tissue oxygenation. With few exceptions, we restricted our selection to
      clinical studies published in the English literature. RECENT FINDINGS: No major
      breakthroughs have occurred in the past decade in the diagnosis or treatment of
      tissue hypoxia. There is renewed interest in goal-directed resuscitation when
      applied early in the course of treatment. Monitoring metabolic markers of tissue
      hypoxia continues to hold great clinical interest, in particular, tissue PCO2,
      near infrared spectroscopy, base deficit and blood lactate concentration.
      Technical issues, however, seem to restrict the widespread use of many of these
      techniques. SUMMARY: There is an urgent need to develop methods to accurately and
      rapidly identify patients with tissue hypoxia. Perhaps the combination of gastric
      tonometry, near-infrared spectroscopy, urinary PO2 and continuous measures of
      mixed (or central) venous O2 saturation may provide the answer. An even more
      formidable task is that of developing effective therapy to correct tissue hypoxia
      while avoiding harm to the patient.

PMID- 17021538
TI  - New aspects of acid-base balance in intensive care.
AB  - PURPOSE OF REVIEW: For 20 years, an alternative view of the universe has been
      available for acid-base physiology. The Stewart approach emphasizes
      mathematically independent and dependent variables. With the Stewart approach
      bicarbonate and hydrogen ions are dependent variables that represent the effects
      rather than the causes of acid-base derangements. Neither bicarbonate nor pH can
      be regulated directly; rather they are controlled by the independent variables.
      In plasma there are three independent variables: the partial pressure of carbon
      dioxide, strong ion difference, and weak acids. In plasma, sodium and chloride
      are the principal strong ions, and albumin is the principal weak acid. Critically
      ill patients often have changes in these variables. RECENT FINDINGS: Recent
      studies have examined various aspects of the Stewart approach, including the
      effects of buffers and haemofiltration as well as bedside assessment of a
      patient's acid-base status. While sodium bicarbonate increases the strong ion
      difference by increasing plasma sodium, tris-hydroxymethyl aminomethane acts by
      increasing plasma weak base concentration and weak cations. Several studies
      support correcting the anion gap for changes in albumin (and even phosphate). One
      study raises a cautionary note on the poor agreement between central laboratory
      and point-of-care measurements of important biochemical variables, including
      plasma sodium and chloride. SUMMARY: The Stewart approach to acid-base physiology
      continues to develop as a comprehensive method to diagnose and manage acid-base
      disorders.

PMID- 17021539
TI  - Disseminated intravascular coagulation and coagulation disorders.
AB  - PURPOSE OF REVIEW: An update on recent developments in diagnosis and treatment of
      disseminated intravascular coagulation. RECENT FINDINGS: Disseminated
      intravascular coagulation is defined as a typical disease condition with
      laboratory findings indicating massive coagulation activation and reduction in
      procoagulant capacity. Clinical syndromes associated with the condition are
      consumption coagulopathy, sepsis-induced purpura fulminans, and viral hemorrhagic
      fevers. Consumption coagulopathy is observed in patients with sepsis, aortic
      aneurysms, acute promyelocytic leukemia, and other disseminated malignancies.
      Sepsis-induced purpura fulminans is characterized by microvascular occlusion
      causing hemorrhagic necrosis of the skin and organ failure. Viral hemorrhagic
      fevers result in massively increased tissue factor production in monocytes and
      macrophages, inducing microvascular thrombosis and consumption of platelets and
      coagulation factors. Current scoring systems do not distinguish between patients
      with asymptomatic disseminated intravascular coagulation, consumption
      coagulopathy and thrombotic syndromes. Patients with sepsis may be identified by
      activated partial thromboplastin time waveform analysis performed as part of
      routine coagulation testing. Drotrecogin alpha (activated) reduces mortality in
      patients with severe sepsis with and without disseminated intravascular
      coagulation and has been used in patients with sepsis-induced purpura fulminans.
      Tifacogin does not reduce mortality in severe sepsis associated with impaired
      coagulation. Patients with heterozygous factor V Leiden mutation and severe
      sepsis showed a lower 28-day mortality than patients without this mutation,
      supporting the assumption that an enhanced level of coagulation activation may be
      beneficial in patients with severe sepsis. SUMMARY: Whereas antithrombin and
      tifacogin failed to improve clinical outcome in severe sepsis, drotrecogin alpha
      (activated) increased the chances of survival of patients with severe sepsis with
      and without disseminated intravascular coagulation.

PMID- 17021541
TI  - The cost of preparedness.

PMID- 17021540
TI  - Stress and stress disorders during and after intensive care.
AB  - PURPOSE OF REVIEW: We provide an overview of the multilevel/multidimensional
      approach to stress and stress disorders, and integrate research findings into the
      intensive care context. Recent findings are discussed within the context of well
      studied biopsychological theories of stress and stress disorders. RECENT
      FINDINGS: The stress response must be viewed as a process. It should be discussed
      in terms of perception, immediate response and prolonged manifestations. There
      are correlations with biological principles, in that neurotransmitters can be
      distinguished on the basis of speed of response, duration of action and range of
      activity. Nevertheless, discussions on vulnerability to stress and the ability to
      cope with stressors are important. Findings regarding the influence of chronic
      stress and dysfunction of the hypothalamo-pituitary axis on stress disorders
      after intensive care encourage us to consider preoperative interventions that
      reduce chronic stress and therefore re-establish proper function of the
      hypothalamo-pituitary axis. SUMMARY: Stress disorders can be viewed as a
      consequence either of the action of humoral substances or of failure to recover.
      Studies on the process of psychophysiological recovery in the intensive care unit
      are urgently needed. Patient factors such as type of illness, age and sex should
      be considered modifiers of the stress response. In addition, the interaction
      between molecular mechanisms of the tissue healing process and the
      psychophysiological stress response require more intensive study.

PMID- 17021542
TI  - Blood substitutes.
AB  - PURPOSE OF REVIEW: Risk of disease transmission and limitations in the ability to
      transfuse in the prehospital or combat setting have stimulated research in the
      field of oxygen therapeutics. Several products have completed safety trials and
      are presently undergoing investigation for their efficacy. In the near future,
      the clinician will likely employ these products in the management of a variety of
      patient populations. Though similar in their oxygen carrying capacity, each agent
      possesses distinct physiologic effects. Understanding of the benefits and
      shortcomings of the various compounds is essential in order to optimally utilize
      them in various clinical settings. This review provides an overview of recent
      developments in the field of oxygen therapeutics and highlights results of
      clinical trials. RECENT FINDINGS: Modified hemoglobin solutions of human or
      bovine origin and perfluorochemical-based emulsions are in advanced stages of
      clinical testing. Bovine hemoglobin-based solutions have been associated with
      vascular reactivity, methemoglobin formation and development of antibodies.
      Larger safety trials are necessary before they can find widespread use.
      Polymerized human hemoglobin solutions have a favorable safety profile in early
      trials and have been effective as a resuscitation fluid in circumstances when red
      cells may be unavailable. Unfortunately, outdated human blood, the substrate for
      this product, is itself in short supply. Perfluorocarbons similarly reduce the
      need for allogeneic transfusion, but the need for high-inspired oxygen levels
      currently limits use. Recombinant, polymer-encapsulated and additional forms of
      chemically modified hemoglobins are being developed and are undergoing testing in
      animal models SUMMARY: Oxygen carriers offer a viable alternative to allogeneic
      transfusion. All oxygen therapeutic agents are not clinically equivalent. Optimal
      utilization requires a thorough understanding of the therapeutic potentials and
      adverse effects of the solution being considered for use.

PMID- 17021543
TI  - Trauma in the pregnant patient.
AB  - PURPOSE OF REVIEW: Trauma is the leading overall cause of death in the age group
      under 40 years of age in the United States. Women of reproductive age are
      considered the population at greatest risk of trauma. A Medline search for recent
      articles highlighting anesthetic, obstetric and surgical considerations for
      pregnant trauma victims was performed, and current guidelines (recommendations)
      are discussed in this review article. RECENT FINDINGS: Trauma in pregnancy is
      currently a leading cause of non-pregnancy-related maternal death, and maternal
      death remains the most common cause of fetal demise. The most common etiologies
      of trauma in pregnancy include transportation accidents, falls, violent assaults,
      and burn injuries. Head and neck injuries and hemorrhagic shock account for most
      maternal deaths secondary to trauma. SUMMARY: Pregnancy must always be suspected
      in any female trauma patient of childbearing age. The pregnant trauma victim
      presents a unique spectrum of challenges to the healthcare team. Expeditious
      maternal resuscitation is the most effective method of fetal resuscitation.
      Adequate management of pregnant trauma victims requires the anesthesiologist to
      consider and understand the unique changes in anatomy and physiology that take
      place during pregnancy.

PMID- 17021544
TI  - Management of blast injuries and shock lung.
AB  - PURPOSE OF REVIEW: Blast injuries have always occurred both in civilian life and
      as acts of war or terrorism. Nowadays, the risk of being involved in an explosion
      has increased even for those living in countries with no previous experience of
      such events. It is our intention that this review is of assistance to those
      providing emergency/critical care to patients who have sustained blast injuries.
      RECENT FINDINGS: Exposure to blast may indirectly produce physiological insults
      such as bradycardia, hypotension, tissue hypoxia and oxidative stress. The use of
      early goal-directed therapy might be important in minimizing such insults.
      Explosions in an enclosed environment are associated with increased risk of
      pulmonary blast injury and also air and fat embolism. Mechanical ventilation
      after pulmonary blast injury is associated with barotrauma and the use of lung
      protective strategies previously recommended in acute lung injury may be
      beneficial. SUMMARY: The potential for blast to cause injury depends on the
      nature of the explosive and environment in which the blast occurs. Soft tissue
      injury with environmental contamination is frequent. Optimal antimicrobial cover
      and strategies such as selective digestive decontamination may be advantageous.
      Early surgery should follow the principles of 'damage control'. Blast injury
      often leads to severe sepsis/systemic inflammatory response, multiple organ
      dysfunction and prolonged critical illness. In this clinical scenario, recent
      studies have shown improved outcome with the use of activated protein C, steroid
      replacement and aggressive control of blood glucose but have been less convincing
      regarding the use of immuno-nutrition.

PMID- 17021545
TI  - Use of recombinant factor VIIa, Novo Seven, in the management of acute
      haemorrhage.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to propose the use of factor VIIa
      in treating severely bleeding patients. RECENT FINDINGS: Recombinant factor VIIa
      was developed in 1988 to treat patients with haemophilia A or B and antibodies
      against factors VIII and IX, or patients with a spontaneous inhibitor against
      factors VIII and IX. Since then factor VIIa has been shown to be very effective
      in treating many other bleeding disorders, such as diverse thrombocytopathias,
      antibodies against other coagulation proteins like factor V, and bleeding as a
      result of oral anticoagulation. SUMMARY: Recombinant factor VIIa may be the
      universal haemostatic agent, but further studies are needed to prove this.

PMID- 17021546
TI  - Management of trauma in the geriatric patient.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine recent evidence on
      the role and significance of anesthesiologists in caring for elderly patients
      suffering from severe trauma. RECENT FINDINGS: Recent findings suggest that early
      aggressive resuscitation and medical management interventions may lead to
      improved outcomes in elderly trauma patients. SUMMARY: Data suggest that
      anesthesiologists should actively participate in the resuscitation and critical
      care management of patients soon after they have suffered significant trauma.
      Further research is needed to delineate specific areas of focus and intervention
      to allow for optimal care and outcomes.

PMID- 17021547
TI  - Payment for procedural sedation.
AB  - PURPOSE OF REVIEW: As surgical procedures become less invasive and medical
      procedures become more invasive, the role of procedural sedation has become more
      important. The resulting proliferation of settings for procedural sedation and
      providers rendering sedation has brought attention to the economics of this
      service from nonanesthesia specialists and payers. Rapidly escalating
      expenditures for sedation have led to scrutiny from public and private insurance
      carriers. The review will summarize these trends and predict changes in coding
      and payment for procedural sedation. RECENT FINDINGS: Changes in coding for
      sedation by proceduralists have raised questions about the value of procedural
      sedation that have implications for anesthesiologists and other specialists
      administering sedatives for their own or others' procedures. The emerging
      literature on the role of registered nurses in administering new sedative agents
      has led to a re-examination of the role of anesthesiologists and other physicians
      in providing this care. Workforce projections demonstrating an ongoing shortage
      of anesthesia and nursing personnel have created a dilemma about the availability
      of professionals to meet the growing need for sedation. A proliferation of
      Medicare medical necessity rules may limit the availability of payment for
      monitored anesthesia care in many settings. SUMMARY: Coding, payment rules and
      fees for procedural sedation are likely to change in the coming 2-5 years. Those
      responsible for providing such services must consider the economic, clinical and
      workforce issues underlying these changes when planning to undertake or expand a
      commitment to sedation.

PMID- 17021548
TI  - Informed consent: ethical implications in clinical practice.
AB  - PURPOSE OF REVIEW: The concept of involving pediatric patients in medical
      decision-making, in both clinical and research anesthesia and surgical care, has
      support from specialists involved in pediatric care. Production pressure in the
      workplace creates conflict between ethical anesthesia practice - such as
      obtaining informed consent - and time efficiency. Specialized documentation of
      anesthesia consent may increase efficiency but could weaken the consent process.
      Concerns with cost containment have led to interventional quality improvement
      activities that may constitute research and therein require informed consent.
      This review discusses these three consent issues as they relate to anesthesia
      care. RECENT FINDINGS: Children are more capable of participating in medical
      decision-making than previously thought. Despite the call for physicians to
      involve children in decision-making regarding their medical care, few physicians
      or parents do so. Quality improvement research potentially harmful to patients,
      achieved without patient knowledge or consent, may violate the Nuremberg Code.
      Opinions differ about the potential advantages and pitfalls of specific and
      separate anesthesia consent forms. SUMMARY: Anesthesiologists have ethical
      obligations to involve children in the medical decision-making process as much as
      the child's capacity allows, and to place patient advocacy in the informed
      consent process above production pressures. While a specific and separate
      anesthesia informed consent form may be useful, it should not undermine the
      process of informed consent or relegate the consent process to non-physician
      personnel. The informed consent process for anesthesia care remains the province
      and responsibility of the individual anesthesiologist.

PMID- 17021549
TI  - Carotid endarterectomy, carotid artery shunting and outcome: an historical
      perspective.
AB  - PURPOSE OF REVIEW: Carotid endarterectomy is now celebrating its 50th
      anniversary! Yet, despite millions of these operations having been performed,
      there is little agreement about the best methods of surgical technique, cerebral
      protection, anesthetic technique and monitoring methods. In this time of evidence
      based medicine, carotid endarterectomy fares badly, with only the indications for
      the surgery having been subjected to the appropriate methodology of clinical
      trials and biostatistics for proper evaluation. This review is designed to look
      back over the history of carotid endarterectomy in order to understand the
      evolution of current practices. RECENT FINDINGS: Within the past 5 years, despite
      the publication of many papers dealing with issues surrounding carotid shunting,
      no randomized controlled trials evaluating this aspect of carotid artery surgery
      have appeared. One must probe further into the past to understand how so much can
      be written yet so little learned! SUMMARY: Current evidence is not able to
      support the hypothesis that shunting during carotid artery surgery reduces the
      risk of perioperative stroke or death or that its use is associated with an
      increase in perioperative or long-term complications. Routine, selective or no
      shunting protocols during carotid artery surgery remain a matter of local custom
      and tradition.

PMID- 17021550
TI  - Current world literature.

PMID- 17021552
TI  - Nitrous oxide: the passing of a gas?

PMID- 17021553
TI  - Recent developments in paediatric regional anaesthesia.
AB  - PURPOSE OF REVIEW: This review will focus on recently published data concerning
      side effects and complications of paediatric regional anaesthesia, putting into
      perspective the currently used techniques. RECENT FINDINGS: Penile block is
      clearly a technique with a very large benefit and minimal side effects.
      Ilioinguinal nerve block, on the other hand, quite commonly leads to
      complications. Single-shot caudal anaesthesia is considered a safe and effective
      technique; however, even with this widely used block, complications such as
      sacral osteomyelitis can occur. Recent review articles have focussed on the role
      of additives for prolonging the duration of paediatric caudal anaesthesia. The
      use of ketamine or s-ketamine as an additive appears to be most promising for the
      future. SUMMARY: Paediatric regional anaesthesia is now widely used for
      postoperative pain relief in children. However, a careful risk-benefit analysis
      is always mandatory before such medical interventions are undertaken.

PMID- 17021554
TI  - The paediatric upper airway: anaesthetic aspects and conclusions.
AB  - PURPOSE OF REVIEW: Paediatric airway problems are among the most challenging
      clinicians will face throughout their career. Clinicians unaccustomed to dealing
      with children tend to approach paediatric airway problems with a disproportionate
      amount of fear that is often engendered by inexperience, and this fear can
      interfere with performance. Understanding the differences between the infant
      upper airway and the airway in older children is important to properly manage the
      airway. RECENT FINDINGS: Airway manoeuvres and the important tools used for
      airway management, such as the laryngeal mask airway, the fibreoptic bronchoscope
      and the new intubating fibreoptic stylets for managing the difficult paediatric
      airway, have been elucidated in the literature. SUMMARY: Planning, preparation,
      and teamwork are essential, and must include an awareness of problems that might
      occur in the recovery period. Special clinical situations such as management of
      the child with impending airway obstruction are discussed.

PMID- 17021555
TI  - Recent developments in the pharmacologic approach to pediatric critical care.
AB  - PURPOSE OF REVIEW: There is new information supporting a resurgence of targeted
      use of older medications. These therapies include hydrocortisone and vasopressin.
      In addition to these older drugs, newer drugs, drotrecogin alpha (activated
      protein C) and activated factor VII concentrate (NovoSeven), have been used and
      may improve outcome in the treatment of critically ill patients. This review
      summarizes the recent experience of these agents in the adult and pediatric
      critically ill populations. RECENT FINDINGS: Preliminary findings are encouraging
      in selected septic children and adults for human recombinant activated protein C
      and protein C concentrate. Plasma vasopressin levels in pediatric septic shock
      and their importance have not yet been adequately studied. Recent evidence
      supports physiologic replacement of corticosteroids in specific adult
      populations. Further investigations are warranted to establish the role of
      activated factor VIIa in the treatment of critically ill children. SUMMARY: The
      limited experience of protein C manipulation in critically ill septic pediatric
      patients makes it difficult to define its role in their care. Although it has
      been associated with improved outcomes, its risk profile warrants judicious use.
      Further prospective pediatric clinical trials are needed to define the role of
      vasopressin in the treatment of pediatric shock and cardiac arrest. The role of
      corticosteroids in the treatment of septic shock in adults and children continues
      to be debated. Activated factor VIIa administration to adult and pediatric
      patients without primary bleeding disorders has been increasing. Further
      investigations are warranted to establish the role of activated factor VIIa in
      the treatment of critically ill children.

PMID- 17021556
TI  - Bispectral index monitoring in pediatric anesthesia.
AB  - PURPOSE OF REVIEW: Anesthetic management guided by bispectral index monitoring
      has been demonstrated to facilitate earlier recovery in adults. Recent
      preliminary data also suggest that titration of drugs to achieve a specific
      bispectral index value may reduce the incidence of intraoperative awareness in
      high-risk adults. It is unclear, however, if this technology will benefit
      children as it is based on an algorithm developed from adults. This article
      reviews the literature on the use of the bispectral index monitor in children.
      RECENT FINDINGS: In recent studies, bispectral index scores were shown to
      correlate well with sedation scores during conscious and deep sedation in
      pediatric patients, and also with end-tidal concentrations of inhalation agents
      in children, although bispectral index values may differ with equipotent doses of
      different agents. Other studies have shown that titrating anesthetic agents to a
      specific bispectral index value during general anesthesia in the pediatric age
      group is associated with the use of lower amounts of anesthetic agents and faster
      recovery from anesthesia in children over 2 years old. However, the utility of
      bispectral index monitoring in infants, particularly those less than 6 months
      old, is questionable, as there is little correlation between bispectral index
      values and other measures of the depth of anesthesia in this subset of patients.
      SUMMARY: Bispectral index monitoring may be used to guide anesthetic
      administration in older children, but its use as a tool for guiding sedation in
      the younger pediatric patient needs further investigation. It may be necessary to
      develop a different bispectral index algorithm for children in the younger age
      groups.

PMID- 17021557
TI  - Fetal surgery, anaesthesiological considerations.
AB  - PURPOSE OF REVIEW: Refined techniques and skills have enabled sophisticated
      prenatal diagnosis in utero and resulted in the newly evolving specialty of fetal
      surgery in a few centres worldwide. Most of the procedures performed today have
      been preceded by extensive experimental research in animals, whereas fetal
      anaesthesia is mainly based on clinical experience and a few studies performed in
      pregnant sheep. RECENT FINDINGS: Major limitations of fetal surgery include the
      high frequency of preterm labour and delivery which may offset any fetal benefit
      of the surgical procedure. The development of more potent tocolytic drugs than
      the drugs currently available may thus be compared to the meaning of potent
      immunosuppressive agents in organ transplantation. Fetal mortality and maternal
      morbidity consequently lead to a more cautious way of treatment, as with the
      development of endoscopic fetal surgery. SUMMARY: The invasive fetal surgery is
      still considered as being in a research stage in most cases. Therefore most
      procedures are performed as minimally invasive, avoiding substantial risks by
      accessing the uterus through minimal openings. Some new devices are under
      investigation for monitoring the myometrial electrical activity and mechanical
      contractility and the fetal electroencephalogram, the continuous monitoring of
      the fetal arterial oxygen saturation, PO2 and PCO2, and for monitoring fetal
      cerebral oxygenation, blood volume and blood flow by near infrared spectroscopy.

PMID- 17021558
TI  - Advances in postoperative care of pediatric cardiac patients.
AB  - PURPOSE OF REVIEW: The past two decades have seen tremendous technological
      advances in the care of infants and children with congenital and acquired heart
      disease. Recent advances in postoperative management have made it possible to
      support smaller and more fragile infants, extended the capabilities of
      extracorporeal circulation, and have brought new and innovative monitoring
      capabilities to the intensive care unit. RECENT FINDINGS: We chose to focus our
      review on four main themes: management of pulmonary hypertension, mechanical
      support of the myocardium, near infrared spectroscopy, and heparin-induced
      thrombocytopenia. SUMMARY: As operative and cardiopulmonary bypass techniques
      have evolved, early complete repair in neonates and repair of more complex
      lesions is now possible, creating new challenges for postoperative care in the
      intensive care unit. Additionally, recognition and management of newly
      appreciated complications is essential.

PMID- 17021559
TI  - Pediatric sedation.
AB  - PURPOSE OF REVIEW: Pediatric sedation continues to evolve. It is an area of
      practice that involves a variety of pediatric subspecialties, the practitioners
      of many of which are not fully aware of what is being done by others involved in
      this care. The purpose of this review is to consider the current status of
      pediatric sedation in general and to discuss the most recent literature
      concerning this practice. Specifically we will discuss the use of new medications
      for pediatric sedation, issues concerning fasting status, issues surrounding the
      effectiveness of sedation, and discharge criteria after sedation. RECENT
      FINDINGS: Propofol sedation is growing rapidly outside of the operating room
      environment. Emergency-medicine and intensive-care providers are regularly
      employing propofol for procedural sedation and reporting its effective use in
      their hands. Also in the emergency-medicine field, evidence is emerging that
      fasting status is not a particularly important factor in the genesis of critical
      events during sedation. Anesthesiologists are evaluating the use of
      dexmedetomidine for sedation of children and new reports describe the advantages
      of deep sedation and anesthesia over moderate sedation for painful procedures.
      Finally an important study shows that a patient's condition on discharge after
      sedation can be improved through the implementation of specific criteria using
      objective scoring techniques. SUMMARY: Anesthesiologists and those outside of
      anesthesiology are employing new potent sedative hypnotic agents to accomplish
      effective pediatric sedation. At the same time, the consensus-generated sedation
      guidelines--particularly with respect to fasting guidelines--are being
      questioned. All of this is occurring in the face of mounting evidence that
      sedation depth needs to be adequate to provide optimal operating conditions and
      patient satisfaction. Regardless of sedation method used, recovery criteria need
      to be carefully considered in order to optimize patient safety.

PMID- 17021560
TI  - Chronic and cancer pain management.
AB  - PURPOSE OF REVIEW: Chronic pain management in children is not recognized and
      treated adequately. The purpose of this review is to recognize some common
      chronic pain problems in children and offer guidelines for their management.
      RECENT FINDINGS: This points to newer research in understanding complex regional
      pain syndromes-type 1 in children. This review will also discuss some recent
      findings regarding pain management techniques in children particularly the use of
      intravenous regional anesthesia for sympathetic blockade for complex regional
      pain syndromes-type 1. Cancer pain and headache with a logical step ladder
      management will be discussed. SUMMARY: Although the under-treatment of chronic
      pain in children is still prevalent, it is important to understand the mechanisms
      and management of common pain problems in children and adolescents.

PMID- 17021561
TI  - How dead is death?

PMID- 17021562
TI  - New and re-emerging infectious diseases: epidemics in waiting.
AB  - PURPOSE OF REVIEW: New and emerging diseases, combined with the rapid spread of
      pathogens resistant to antibiotics and of disease-carrying insects resistant to
      insecticides, are daunting challenges to human health. RECENT FINDINGS: The new
      diseases of recent months are West Nile virus conquering the American continent,
      the introduction of monkeypox in the USA, the emergence of the severe acute
      respiratory syndrome worldwide, and avian influenza which crossed the species
      barrier again to claim several victims. SUMMARY: Emerging infectious diseases are
      almost instantaneously a global concern because of the speed with which people,
      animals and products move around the world. In order to adapt to these new
      threats, there is a need for timely identification and reporting, the need to
      consider health problems from a global perspective, and the need to incorporate
      practising physicians in the process as much as possible.

PMID- 17021563
TI  - Anesthetic complications of gross obesity.
AB  - PURPOSE OF REVIEW: The number of obese patients undergoing anesthesia and surgery
      is increasing. This article aims to present recent achievements in the management
      of gross and morbidly obese patients in order to improve safety. RECENT FINDINGS:
      Current investigations have demonstrated that the type of anesthesia (total
      intravenous anesthesia or volatile) and the anesthetics used have an important
      influence on the perioperative period, especially on postanesthesia recovery and
      respiratory failure during the postoperative period. These findings were compared
      with previous publications. Practical advice is also presented for performing
      successful intubation and mechanical ventilation in the morbidly obese patient,
      as well as describing drug dosage and administration. SUMMARY: The progress in
      anesthesia techniques and modern drugs allows for safe management of obese
      patients, with mortality decreasing in this group of patients.

PMID- 17021564
TI  - Anaesthesia in patients with dementia.
AB  - PURPOSE OF REVIEW: The next couple of decades will be characterized by an
      increase in life expectancy, leading to an older population. As the incidence of
      Alzheimer's dementia and vascular dementia is rising with age, the future
      anaesthesiologist will be increasingly confronted with perioperative care of
      patients with impaired cognitive function. This paper tries to highlight some
      topics specifically related to demented patients. RECENT FINDINGS: Psychometric
      testing and behaviour vary according to the type of dementia. Neuroanatomical and
      biochemical correlates for different types of dementia are more precise and
      better documented. Evidence exists that cognition may be impaired for weeks after
      anaesthesia, but the mental capacities of those who have undergone surgery are
      comparable to those of age controls in the long term. Most research efforts are
      focused on improving the daily functioning of people with cognitive impairment.
      Several new anticholinesterases are being evaluated. It is advantageous to keep
      cognition optimal throughout the perioperative period. Neuroleptics may be badly
      tolerated and, most importantly, pain pathways may be differentially affected in
      dementia. SUMMARY: Anaesthesia in the demented patient may be complicated by a
      number of potential problems, including the comorbid pathology, the concomitant
      anticholinesterase activity, the need for normoventilation, monitoring of
      anaesthesia depth and the evaluation of postoperative pain. Anaesthesia in
      variant Creutzfeldt-Jakob disease is aimed at preventing the spread of the
      causing prion. There is a broad consensus that early return to the preoperative
      level of cognition is to be pursued, with the help of short-acting drugs and loco
      regional anaesthesia.

PMID- 17021565
TI  - Living-related liver transplantation: implication for the anaesthetist.
AB  - PURPOSE OF REVIEW: Living donor liver transplantation, originally introduced
      about a decade ago to overcome paediatric cadaveric organ shortage, has rapidly
      gained acceptance within the transplant community and is nowadays almost
      routinely applied to the growing number of adult and paediatric patients awaiting
      a live-saving liver transplantation. In fact its introduction has contributed to
      a continuing decrease of waiting list deaths. RECENT FINDINGS: The risk of
      potential complications and even death for the donor increases with the extent of
      liver tissue resected. Better preoperative evaluation of suitability, refinement
      of surgical technique and smarter anaesthetic management, based on extended
      knowledge of underlying pathophysiology, have made the procedure safer for
      donors, with low morbidity and even lower mortality rates, tending towards zero
      in experienced centres. Despite these improvements, a certain risk is inherent.
      Yet from an ethical point of view it has to remain unacceptable especially
      because donors are otherwise healthy people and their only motives are
      altruistic. The procedure of living donor liver transplantation like conventional
      liver transplantation involves various disciplines, each of which contributes in
      a specific manner. There is a broad scope of issues that anaesthetists are
      responsible for and these largely depend on the department and hospital
      requirements. These issues may range from perioperative anaesthetic management
      and pain relief, to--and there are definite continental differences--the
      coordination of donor evaluation, intensive care management, postoperative
      complication management, as well as psychological support for donors, recipients
      and their relatives. SUMMARY: In this paper we review and summarize the potential
      impact of findings and advances made in this particular field as described by the
      most important articles published during the past year.

PMID- 17021566
TI  - Current world literature.

PMID- 17021568
TI  - Obstetric anaesthesia: are times changing?

PMID- 17021569
TI  - Low-dose spinal anaesthesia for caesarean section.
AB  - PURPOSE OF REVIEW: The literature on the appropriate dose of local anaesthetic
      and combinations with opioids for spinal anaesthesia for caesarean section in
      patients without comorbid conditions is reviewed. The controversial issue of
      spinal anaesthesia in severe preeclampsia is also addressed. RECENT FINDINGS:
      Recent comparisons with ropivacaine and levobupivacaine suggest that bupivacaine
      remains the best agent for spinal anaesthesia for caesarean section. The addition
      of various combinations of opioids has allowed a reduction in the dose of
      bupivacaine. Intrathecal diamorphine has been extensively investigated and
      appears to have a favourable pharmacokinetic and pharmacodynamic profile. In
      severe preeclampsia, spinal anaesthesia may be associated with less hypotension
      than in healthy parturients, where similar doses of local anaesthetic are used.
      SUMMARY: Low-dose spinal anaesthesia has been advocated in the interests of
      improving cardiovascular stability. However, current sophistication of knowledge
      concerning spinal anaesthetic technique makes cardiovascular instability easy to
      prevent. Therefore this review emphasizes the importance of adequate surgical
      anaesthesia during caesarean section, and makes suggestions as to the optimal
      pharmacological agents for intraoperative anaesthesia and postoperative
      analgesia. Spinal anaesthesia is safe in severe preeclampsia, provided there are
      no contraindications to regional anaesthesia.

PMID- 17021570
TI  - Fetal effects of maternal supplementary oxygen during Caesarean section.
AB  - PURPOSE OF REVIEW: This review summarises the current issues, knowledge and
      research on the effects of maternal supplementary oxygen therapy on the fetus
      during Caesarean section. This is a controversial subject since supplementary
      oxygen has the potential to confer both benefits and also harm to the fetus,
      depending on the circumstances. RECENT FINDINGS: For elective Caesarean section,
      breathing room air under regional anaesthesia or 30% oxygen under general
      anaesthesia is not associated with either maternal or fetal hypoxia. A prolonged
      uterine-incision-to-delivery (U-D) interval of up to 310 s is not a major factor
      per se for development of fetal hypoxia or acidosis, and no benefits could be
      derived from breathing supplementary oxygen in this situation. Although it
      appears rational to provide supplementary oxygen in the presence of a hypoxic or
      compromised fetus, to achieve meaningful increases in fetal oxygenation, a very
      high inspired oxygen fraction (FiO2) is required. However, it still remains
      unclear whether this is beneficial for the fetus. The process of damage to the
      hypoxic fetus is one of oxidative stress mediated by free radicals generated
      during reperfusion (ischaemia-reperfusion injury). Independently, hyperoxia from
      breathing supplementary oxygen also induces formation of free radicals by direct
      mitochondrial electron transfer. Although hyperoxia could lessen the severity of
      fetal hypoxia, there is also a theoretical risk of an enhanced reperfusion
      injury. This issue has not been resolved in a clinical study, but an animal study
      reported enhanced formation of free radicals after an episode of fetal hypoxia in
      the group receiving supplementary oxygen. SUMMARY: For elective Caesarean
      section, current evidence suggests that supplementary oxygen is unnecessary. For
      emergency Caesarean section, further data are required before a conclusion can be
      made for its beneficial and adverse effects. Improvement of fetal oxygenation
      should be the primary objective, and this is achievable in the short term by
      using a very high FiO2. Although there is also a possibility of an enhanced
      reperfusion injury, particularly in the preterm and non-labouring patients,
      further data are necessary before a conclusion can be made.

PMID- 17021571
TI  - Fetoscopic surgery: where are we today?
AB  - PURPOSE OF REVIEW: Since the early 1990s, advances in endoscopic equipment and
      the commercial availability of micro-catheters, mini-balloons, tiny laser fibers
      and other ingenious tools have set the trend toward the development of minimally
      invasive fetoscopic surgical techniques for the treatment of some congenital
      malformations that progress in severity over the course of gestation and may
      destroy entire organ systems of the unborn. The purpose of this review is to
      provide a state-of-the-art overview of these new procedures for the
      anesthesiologist. RECENT FINDINGS: Procedures like diagnostic fetoscopies, laser
      coagulation of inter-twin placental vascular connections in twin-twin transfusion
      syndrome, fetal tracheal balloon occlusion in diaphragmatic hernia, laser
      perforation of posterior urethral valves, vocal cord division in congenital high
      airway obstruction syndrome and most recently even coverage of spina bifida
      aperta can be performed entirely percutaneously using minimally invasive
      fetoscopic techniques. Careful selection of anesthetic methods and intensive
      maternal monitoring by the anesthesiology team are paramount to the success of
      these procedures, particularly in hemodynamically unstable fetuses or procedures
      that employ gas insufflation of the amniotic cavity. SUMMARY: An increasing
      spectrum of congenital malformations can be treated by fetoscopic surgery.
      Compared to open fetal surgery, fetoscopic surgery results in significantly less
      maternal trauma. Like the open procedures, the efficacy of the fetoscopic
      procedures to improve fetal outcome over postnatal treatment strategies will have
      to be assessed in further studies under close supervision of committees for human
      research.

PMID- 17021572
TI  - Morbidity and mortality related to anaesthesia outside the operating room.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide information related
      to morbidity and mortality associated with anaesthesia outside the operating
      room. RECENT FINDINGS: There is an increasing demand for anaesthesia at remote
      locations. Because of its specific characteristics, resulting from the location
      and the patient, morbidity and mortality rates of remote location anaesthesia
      could differ from conventional operating room anaesthesia. However, no studies
      are currently available. On the basis of morbidity and mortality data from
      conventional operating room anaesthesia, we reached some important conclusions
      with regard to the safety of anaesthesia outside the operating room. A well
      equipped anaesthesia machine, standard monitoring (electrocardiogram, oxygen
      saturation and non-invasive blood pressure), trained personnel and adequate
      planning should be standard for all out of the operating room procedures. When
      all these are in place, the incidence of morbidity or mortality should be
      comparable to that of anaesthesia provided in the operating room. SUMMARY: There
      is certainly a need for studies concerning morbidity and mortality at remote
      location anaesthesia. Special care for the prevention of hypothermia should be
      given to those patients undergoing long-lasting diagnostic procedures, e.g.
      magnetic resonance imaging scans or cardiological investigations.

PMID- 17021573
TI  - New developments in the transcatheter treatment of congenital heart disease.
AB  - PURPOSE OF REVIEW: This review summarizes recent developments in the field of
      interventional paediatric cardiology. This is a rapidly evolving field with many
      new techniques that have been optimized or introduced during the past few years.
      RECENT FINDINGS: Important new data have emerged on the device closure of atrial
      septal defects, ventricular septal defects and patent ductus arteriosus. The
      technology has been improved further and more results on complications and
      problems have become available. New technical developments in the treatment of
      stenosis of the pulmonary arteries and the aorta, such as the use of cutting
      balloons and (covered) stents, have resulted in new treatment options for
      congenital disorders that were not considered suitable for percutaneous
      treatment. Fascinating emerging technologies such as percutaneous aortic and
      pulmonary valve implantations have been introduced and the first results have
      been reported. Changes in imaging technology such as intracardiac
      echocardiography and magnetic resonance imaging affect interventional cardiology.
      These changes result in a new approach to congenital heart disease in which
      hybrid surgical and interventional procedures are used to treat complex disease.
      SUMMARY: Interventional congenital cardiology is a rapidly growing field that
      offers new treatment options for patients with congenital heart disease.

PMID- 17021574
TI  - Anaesthesia for children with congenital heart disease undergoing diagnostic and
      interventional procedures.
AB  - PURPOSE OF REVIEW: Anaesthesiologists are often asked to administer sedation and
      anaesthesia to infants and children with congenital heart disease undergoing
      diagnostic and interventional procedures. A number of issues are pertinent to a
      safe and effective provision of care for these patients. The anaesthetic should
      ensure haemodynamic stability, provide real-life circumstances to ensure
      diagnostic accuracy, should be easy and reliable to titrate in order to cope with
      rapidly changing loading conditions and intense but short-lived haemodynamic
      disturbances. The anaesthetic drugs should not interfere with
      electrophysiological processes in the cardiac conduction system, and above all
      anaesthetic recovery should be swift and devoid of side-effects. RECENT FINDINGS:
      In recent years, new agents have been introduced in the anaesthetic care of these
      patients. One has studied the haemodynamic and electrophysiological properties of
      agents such as remifentanil, desflurane, sevoflurane and propofol and their use
      in children with congenital heart disease. New and older drugs have been combined
      in balanced techniques to decrease the side-effects associated with monotherapy.
      Besides these anaesthetic concerns, the controversy about the presence of an
      anaesthesiologist versus a non-anaesthesiologist still continues. SUMMARY: The
      newer anaesthetic agents, such as desflurane, remifentanil, sevoflurane and
      propofol are an integral part of our armamentarium to care for children with
      congenital heart disease. The combination of these and older drugs allow us to
      provide anaesthetic care in an effective and efficient way.

PMID- 17021575
TI  - Anesthesia for magnetic resonance imaging.
AB  - PURPOSE OF REVIEW: This review focuses on the technological principles, safety
      considerations, monitors and equipment, patient issues, and a general overview of
      the anesthetic management of both conventional and intraoperative magnetic
      resonance imaging based on the most recent literature. RECENT FINDINGS: As a
      diagnostic imaging modality, magnetic resonance imaging remains unparalleled in
      its diagnostic and clinical value. The clinical applications for magnetic
      resonance imaging continue to evolve, and include its latest use in minimally
      invasive procedures as well as in the operating room. Intraoperative magnetic
      resonance imaging is steadily gaining acceptance for neurosurgical procedures.
      The safety considerations, monitor and equipment issues for intraoperative
      magnetic resonance imaging are similar to the conventional setting. However, they
      differ in their focus on anesthesia management. Most monitoring compatible with
      magnetic resonance imaging has been available for many years. In the USA, the
      newest available monitoring option during magnetic resonance imaging is for
      temperature. This option has been available in other countries for a number of
      years. A fiberoptic surface sensor provides a safe and accurate monitor of adult,
      pediatric, and neonatal body temperature. SUMMARY: The magnetic resonance imaging
      suite is a challenging environment for the anesthesiologist, and carries inherent
      risks. Several factors account for this, including the remote location, the
      unique features of the magnetic resonance imaging scanner, and patient-related
      factors. Understanding the implications of the magnetic resonance imaging
      environment will facilitate ensuring the safety of the patient and personnel.

PMID- 17021576
TI  - Current world literature.

PMID- 17021578
TI  - Low birth weight and endocrine dysfunction in postnatal life.
AB  - Small size at birth has long been recognized as a factor increasing neonatal
      morbidity and mortality. During the last decade, reduced growth in early life has
      also been strongly linked with a number of endocrine dysfunctions. Included among
      the most important alterations are insulin insensitivity, gonadal and
      somatotropic axis abnormalities and premature adrenarche. These have been
      associated with an escalating prevalence of T2DM and CHD abnormal gonads and
      genitalia, growth hormone resistance and decreased growth as well as early
      puberty. The usual hypothesis proposed to explain the development of these long
      term alterations relates to the thrifty phenotype as an adaptive response to in
      utero malnutrition and modifications thereof; called "Fetal Origins" and updated
      to "Developmental Origins" which include the additional contributions of the
      patterns of growth in infancy and childhood. In this paper the factors that
      participate in the programming of the fetus and infants that lead to endocrine
      dysfunction in postnatal life is reviewed.

PMID- 17021579
TI  - Children born small for gestational age (SGA) who fail to achieve catch up growth
      by 2-8 years of age are short from infancy to adulthood. Data from a cross
      sectional study of 486 Spanish children.
AB  - AIMS AND METHODS: Postnatal growth was evaluated in a cross-sectional study of
      486 Spanish children, 241 girls and 245 boys, born small for gestational age
      (SGA), without height catch-up growth between the ages of 2 and 8 years [height <
      2SD of age- and sex-matched controls born appropriate for gestational age (AGA)].
      SGA was defined as birth weight and/or length values <-2SD of those of the born
      AGA control population. Weight and height values were grouped in 0.5+/-0.15-year
      intervals from birth to adult height and compared with those of age- and sex
      matched controls born AGA. A total of 1,985 height measurements were recorded in
      girls and 2,113 in boys. Adult or near-adult height was reached in 50 girls and
      42 boys. Mean, SD and mean Z-score values at each age interval were calculated.
      Dysmorphic syndromes and chronic illnesses were excluded. RESULTS: Mean height Z
      score values ranged from -5.56 to -3.12 during the first two years of life and
      remained between -5.25 and -2.42 thereafter until adult height, and mean weight Z
      score values ranged from -3.66 to -2.26 from birth to two years of age and
      remained between -3.05 and -0.94 thereafter until adult height. Mean Z-score
      values of near-adult or adult height were -2.83 in girls (n=50) and -2.74 in boys
      (n=42). Midparental adult height corrected for sex was -1.45 +/- 0.5 in girls
      (n=150) and -1.60 +/-0.6 in boys (n=185). Height +2SD values of SGA children were
      similar to -2SD values of age- and sex-matched AGA controls (non statistically
      significant). CONCLUSIONS: Our data show that short children born SGA are shorter
      than children born AGA from the age of two years onwards and that their adult
      height is below that of their corresponding midparental height by more than 1 SD.

PMID- 17021580
TI  - Inactivating mutations of LH and FSH receptors--from genotype to phenotype.
AB  - The pituitary glycoprotein hormones, LH and FSH, and their receptors are
      essential for normal reproductive function in both sexes. Over the past 10 years,
      several inactivating mutations of the gonadotropin receptors have been described
      in rare forms of human primary gonadal disorders. Homozygous or compound
      heterozygous inactivating mutations of the LH receptor were associated with a
      rare autosomal recessive form of male pseudohermaphroditism (Leydig cell
      hypoplasia), micropenis and hypergonadotropic hypogonadism in genetic males. In
      addition, these mutations caused primary or secondary amenorrhea and infertility
      in women who were sisters of male pseudohermaphrodites. Similarly, FSH receptor
      inactivating mutations were associated with partial or complete phenotypes of
      premature ovarian failure in women. These inactivating mutations corroborate and
      extend our knowledge of clinical consequences of gonadotropin resistance and
      inappropriate gonadotropin action. In addition, the characterization of the
      molecular basis of gonadal resistance can be useful for directing therapy and for
      genetic counseling.

PMID- 17021582
TI  - Osteogenesis imperfecta and its molecular diagnosis by determination of mutations
      of type I collagen genes.
AB  - Osteogenesis Imperfecta is a genetic disorder of increased bone fragility and low
      bone mass. Most cases are caused by a mutation in one of the two genes coding for
      the type I collagen protein. The correct clinical diagnosis of OI can be
      difficult sometimes, because of the wide phenotypic range. Therefore collagen I
      genes mutation identification can be helpful. We screened 23 patients by direct
      sequencing of the exons encoding the collagen protein. We identified 18 different
      mutations, while 5 cases were negative because of an uncertain clinical diagnosis
      or an atypical form of OI not related to collagen I genes. The current medical
      and pharmaceutical treatments are only symptomatic and do not alter the course of
      collagen mutations. Cells and gene therapies as potential treatments for OI have
      therefore to be actively investigated.

PMID- 17021581
TI  - Adrenocortical tumors and hyperplasias in childhood--etiology, genetics, clinical
      presentation and therapy.
AB  - Adrenocortical tumors are rare in children and are associated with a poor
      prognosis when malignant. The fund of knowledge regarding etiology, presentation
      and clinical outcomes remains limited. Evaluation of genetic disorders associated
      with the development of adrenocortical disorders has allowed researchers to
      identify a number of mutations that may be involved in tumorigenesis, including
      alterations in the GNAS1, PRKAR1A, TP53 and IGF2 genes. Clinical presentation in
      children is associated most commonly with young age, female gender and symptoms
      of virilization. Most children have localized disease at presentation which may
      be associated with a better prognosis when compared to adults. Surgical resection
      remains the only potentially curative treatment and mitotane, the most frequently
      used chemotherapeutic agent, has a poor response rate and is highly toxic.
      Broader participation in multi-center research, such as the International
      Pediatric Adrenocortical Tumor Registry, is needed to collect sufficient data to
      better guide our clinical management.

PMID- 17021583
TI  - Quality of life in aphasia: Greek adaptation of the stroke and aphasia quality of
      life scale - 39 item (SAQOL-39).
AB  - AIM: Health-related quality of life (HRQL) measures are becoming increasingly
      popular in evaluating health care interventions and services. The stroke and
      aphasia quality of life scale-39 item (SAQOL-39) is an English questionnaire that
      measures HRQL in people with aphasia. There is currently no measure to assess the
      HRQL of Greek-speaking people with aphasia. This study began the cross-cultural
      adaptation of the SAQOL-39 into Greek, by translating and linguistically
      validating the instrument. METHODS: The Mapi approach to linguistic validation
      was followed. The SAQOL-39 was forward translated into Greek and back-translated
      into English. The pilot version was produced by comparing the forward and
      backward translations. The resulting instrument was then reviewed by an expert
      professional and pilot tested with a sample of 10 people with aphasia. RESULTS:
      Sixty-seven percent of back-translated items matched those in the original
      instrument. Only 20% of the items in the consensus version needed amendments for
      the pilot version. The pilot testing showed that the SAQOL-39 had good
      accessibility (no missing data), acceptability (maximum endorsement frequencies,
      MEF=or>70%; 9 out of 10 participants had no difficulty) and content validity (8
      participants had nothing to add to the questionnaire). CONCLUSIONS: By employing
      the Mapi approach to linguistic validation, a close matching between the original
      and the Greek version of the SAQOL-39 was ensured. The Greek SAQOL-39 is
      accessible and acceptable to people with aphasia. Further research is needed on
      the psychometric properties of the Greek SAQOL-39 and on its appropriateness as a
      clinical outcome measure.

PMID- 17021584
TI  - Functional outcome of botulinum toxin injection of gastrocnemius and adductors in
      spastic hemiplegic cerebral palsied children.
AB  - AIM: The aim of this paper was to compare between the various effects of
      botulinum toxin type A (BT-A) when it is injected at gastrocnemius or adductors
      or at both sites in ambulant spastic hemiplegic cerebral palsy (CP) children.
      METHODS: Sixty ambulant CP children with spastic hemiplegia were chosen. They
      were divided into 4 equal homogenous groups. Study groups (A, B, and C) received
      3 successive injections of BT-A at 3 to 4 months interval. The injection sites
      were as follows: gastrocnemius for group A; adductors for group B; gastrocnemius
      and adductors for group C. Group D received no injections and was considered as a
      control group. Muscle tone and gait evaluation were conducted for every child in
      the BT-A groups at his entry and 6 months after the last injection dose. Also,
      the same evaluation protocol was conducted for every child in the control group
      at his entry and after 6 month's period. RESULTS: When BT-A groups were compared
      to the control group, results showed significant improvement in muscle tone
      following injection in all BT-A groups. A statistically significant increase of
      the unaffected step length and decrease of step width and foot angle was noted in
      gastrocnemius group (P=0.04, P=0.003, P=0.002) respectively, as well as in
      gastrocnemius/adductors group (P=0.006, P=0.002, P=0.003), respectively. However,
      the cadence and speed of walking showed significant increase in the
      gastrocnemius/adductors group; only P=0.03, P=0.004 respectively. Comparing
      between BT-A groups, there was significant improvement in all parameters between
      adductors and gastrocnemius/adductors groups in favor of the last group.
      Moreover, there was significant improvement in muscle tone (P=0, cadence P=0.04),
      and speed of walking P=0.01 between gastrocnemius and gastrocnemius/adductors
      groups in favor of the last group; however, there was no significant difference
      between these 2 groups in respect to the step width P=0.96 and the foot angle
      P=0.92. CONCLUSIONS: Our findings indicate that, in spastic hemiplegic CP,
      botulinum toxin has a better effect on tone reduction and improvement of gait
      parameters when it is given at the gastrocnemius and adductors muscles
      collectively.

PMID- 17021585
TI  - The use of desmopressin in the management of nocturnal enuresis in patients with
      spinal cord injury.
AB  - AIM: The aim of this study is to evaluate the use of desmopressin acetate (DDAVP)
      in the management of nocturnal enuresis in patients with spinal cord injury
      (SCI), as well as arginine vasopressin (AVP) daily production, urine output,
      urine osmolarity and clean intermittent catheterization (CIC) before and after
      the use of desmopressin. METHODS: We studied 11 patients with SCI (7 men 4
      women). All patients attended a rehabilitation program and used a wheelchair for
      locomotion. To improve bladder function and achieve socially acceptable
      continence all patients were placed on a regimen of anticholinergic drugs
      (oxybutynin 5 mg, 1x3 daily), evening antibiotic prophylaxis and CIC. The
      subjects were also on night CIC in order to avoid nocturnal incontinence. DDAVP
      was given intranasally (20 mg before bedtime) in association with other standard
      therapy. Urine samples were collected under sterile conditions from all patients
      at 6:00 a.m. and 6:00 p.m. Urine volume was measured and the amount of urine per
      hour was calculated. Blood samples were also taken to measure serum AVP, urea,
      creatinine and serum electrolyte. RESULTS: Our data suggest that nocturnal
      polyuria in SCI patients occurs due to a lack of diurnal variation of
      antidiuretic hormone (ADH) secretion. The use of desmopressin produced a
      statistically significant increase in urine production rate during the day (56.2
      vs 81.2 mL/h, P<0.001) and a decrease in nocturnal urine production (59.2 vs 27.7
      mL/h, P<0.001). Desmopressin treatment reflects also on urine osmolarity, which
      did not change during the day (496 vs 489 mOsm/mL, P>0.5) but showed a
      significant increase during the night (385 vs 862 mOsm/mL, P<0.001). There was a
      significant decrease in night CIC. No serious adverse effects were observed.
      CONCLUSION: Our results suggest that desmopressin administration is an beneficial
      treating option for patients with SCI when fluid restriction and other preventive
      measures are not able to control abnormal nocturnal polyuria.

PMID- 17021586
TI  - European physical and rehabilitation medicine organisms--origins and
      developments.

PMID- 17021587
TI  - Increase of the heat pain threshold during and after high-frequency
      transcutaneous peripheral nerve stimulation in a group of normal subjects.
AB  - AIM: Transcutaneous electrical nerve stimulation (TENS) is used worldwide for
      pain relief, but its mechanisms of action are not completely understood. High
      frequency transcutaneous peripheral nerve stimulation (HF-TPNS) is a term
      describing a type of TENS where a peripheral nerve is stimulated
      transcutaneously. The aim of the investigation was to verify the hypothesis that
      HF-TPNS increases the heat pain threshold in the skin territory of the stimulated
      nerve, during and after stimulation. METHODS: Eighteen volunteers (8 men, 10
      women) participated in 2 sessions conducted on different days. In each session
      their heat pain thresholds were measured in basal conditions and after 5, 10, 15,
      25, 40, 70 min. In one session, HF-TPNS was delivered for 10 min immediately
      after basal evaluation (HF-TPNS session). In the other session the heat pain
      thresholds only were measured (control session). The superficial radial nerve was
      stimulated at the wrist (frequency of 100 Hz, pulse duration of 0.1 ms). The heat
      pain threshold was studied using a contact thermode (surface of 12.5 cm(2))
      placed in the cutaneous area of the stimulated nerve at the site where the
      paresthesia evoked by electrical stimulation could be felt. RESULTS: HF-TPNS
      significantly increased the heat pain threshold both during and after
      stimulation. CONCLUSION: This study confirms that HF-TPNS induces an important
      hypoalgesic effect. The prolonged duration of poststimulation hypoalgesia (60
      min) indicates that continuous stimulation is probably unnecessary. Further
      studies are needed to test the hypothesis that intermittent HF-TPNS is able to
      maintain its hypoalgesic effectiveness over time.

PMID- 17021588
TI  - Assessment and correlation between clinical patterns, disability and health
      related quality of life in patients with low back pain.
AB  - AIM: Low back pain (LBP) is the main symptom of most lumbar spine diseases. This
      symptom, due to physical, psychological and social factors, is correlated to a
      real disability which can affect the quality of life (QoL.) The aim of this study
      is to evaluate the QoL and the disability in patients with LBP and to correlate
      them to clinical patterns. METHODS: In this prospective multidimensional study,
      108 patients underwent the following protocol: 1. collection of patient-oriented
      and disability data with the use of SF-36 and North American Spine Society
      (NASS); 2. collection of clinical, anamnestic and instrumental data (MRI, CT)
      with the use of DOVAC files; 3. assessment of disability with the use of Barthel
      index (BI) and deambulation index (DI). RESULTS: A significant correlation was
      found between the BI and the physical composite score (PCS), but no significant
      correlation was noticed between BI and the mental composite score (MCS). DI was
      not correlated to the SF-36. A positive Lasegue and the absence of the osteo
      tendinous reflexes are significantly correlated to the disability and QoL.
      CONCLUSIONS: This study shows that there is no simple, linear correlation between
      QoL and disability.

PMID- 17021589
TI  - Gait rehabilitation: a new biofeedback device for monitoring and enhancing weight
      bearing over the affected lower limb.
AB  - AIM: Gait rehabilitation programs often require either partial weight-bearing
      (PWB) or encourage full weight-bearing (FWB) on the affected limb. Until
      recently, there was no objective and practical way to measure correct weight
      bearing during ambulation. The present study evaluates a new in-shoe device
      (SmartStep, Andante Medical Devices Ltd.) for measuring the amount of weight on
      the affected limb and for biofeedback gait training. METHODS: The first part of
      the study aimed to establish the validity of the SmartStep by comparing the
      results obtained from this device with the results obtained from a force plate.
      The second part aimed to evaluate the effectiveness of the SmartStep as a
      biofeedback method in patients who have been referred for FWB gait
      rehabilitation. Analysis was based on independent samples t-test and chi squared
      test for evaluating statistically significant differences between the 2 gait
      rehabilitation modes. RESULTS: The SmartStep could repeat the same results with
      0.53 kg error of mean. Statistically significant correlation was found between
      results obtained from the SmartStep and from the force plate (R2=0.9067 and
      P=0.004). The use of the SmartStep auditory biofeedback, significantly
      (P=0.00031) improved patients' weight-bearing over the affected limb in the
      experimental group (7.9 kg +/-5.28) as compared to the control group (0.7+/-2.41
      kg). CONCLUSIONS: The SmartStep proved to be very reliable since it generated
      significant repeatable results which correlated significantly with those obtained
      from a force plate. Patients recommended for FWB gait can significantly improve
      body weight loading over the affected limb by the use of the SmartStep auditory
      biofeedback.

PMID- 17021590
TI  - Childhood influenza vaccination coverage--United States, 2004-05 influenza
      season.
AB  - Children aged <2 years are at increased risk for influenza-related
      hospitalizations, and children aged 24-59 months are more likely than older
      children to visit a clinic, hospital, or emergency department with influenza
      associated illness. In 2002, the Advisory Committee on Immunization Practices
      (ACIP) encouraged annual influenza vaccinations for children aged 6-23 months
      (and for household contacts of and out-of-home caregivers for children aged <2
      years). For the 2004-05 influenza season, ACIP strengthened its encouragement to
      a full recommendation. For the upcoming 2006-07 influenza season, ACIP has
      further extended its recommendation to include all children aged 6-59 months (and
      their household contacts and out-of-home caregivers). Others recommended to
      receive influenza vaccination include children aged 6-18 years who have certain
      high-risk medical conditions, are on chronic aspirin therapy, or who are
      household contacts of persons at high risk for influenza complications. This
      report provides an assessment of influenza vaccination coverage among children
      aged 6-23 months during the 2004-05 influenza season. The findings demonstrate
      that vaccination coverage in that age group approximately doubled from the 2003
      04 influenza season, with substantial variability among states and urban areas.
      However, the percentage of fully vaccinated children remained low, underscoring
      the need for increased measures to improve pediatric vaccination coverage and
      ongoing monitoring of coverage among young children and their close contacts.

PMID- 17021591
TI  - Influenza and pneumococcal vaccination coverage among persons aged > or = 65
      years--United States, 2004-2005.
AB  - Vaccination of persons at increased risk for complications from influenza and
      pneumococcal disease is a key public health strategy in the United States. During
      the 1990-1999 influenza seasons, approximately 36,000 deaths were attributed
      annually to influenza infection, with approximately 90% of deaths occurring among
      adults aged > or = 65 years. In 1998, an estimated 3,400 adults aged > or = 65
      years died as a result of invasive pneumococcal disease. One of the Healthy
      People 2010 objectives is to achieve 90% coverage of noninstitutionalized adults
      aged > or = 65 years for both influenza and pneumococcal vaccinations (objective
      14-29). To assess progress toward this goal, this report examines vaccination
      coverage for persons interviewed in the 2004 and 2005 Behavioral Risk Factor
      Surveillance System (BRFSS) surveys. The 2004-05 influenza season was
      characterized by an influenza vaccine shortage. As a result, the Advisory
      Committee on Immunization Practices (ACIP) issued recommendations that influenza
      vaccine be reserved for persons in priority groups, including persons aged > or =
      65 years, and that others should defer vaccination until supply was sufficient.
      The results of this assessment indicated that, overall, influenza vaccination
      coverage was lower in the 2005 survey year than in 2004, whereas pneumococcal
      vaccination coverage was nearly unchanged from 2004 to 2005. In both years,
      influenza and pneumococcal vaccination coverage varied from state to state.
      Continued measures are needed to increase the proportion of older adults who
      receive influenza and pneumococcal vaccines; health-care providers should offer
      pneumococcal vaccine all year and should continue to offer influenza vaccine
      during December and throughout the influenza season, even after influenza
      activity has been documented in the community.

PMID- 17021592
TI  - Outbreaks of multidrug-resistant Shigella sonnei gastroenteritis associated with
      day care centers--Kansas, Kentucky, and Missouri, 2005.
AB  - Infection with Shigella sonnei that is resistant to antibiotics commonly used in
      pediatric practice has become more common during the past decade. In 2005,
      Kansas, Kentucky, and Missouri reported increases in shigellosis cases associated
      with day care centers caused predominantly by multidrug-resistant (MDR) (i.e.,
      resistant to ampicillin and trimethoprim-sulfamethoxazole [TMP/SMX]) strains of
      S. sonnei. Pulsed-field gel electrophoresis (PFGE) patterns for isolates from
      Kansas and Missouri were similar, suggesting a common outbreak in the Kansas City
      area, whereas isolates from Kentucky had a different pattern. This report
      describes the investigation of two outbreaks of MDR shigellosis associated with
      day care centers and reviews measures for prevention and control of S. sonnei
      infection in these settings. Given the current rates of resistance to antibiotics
      available to treat children with shigellosis safely, public health measures
      initiated during shigellosis outbreaks should focus on promoting appropriate
      handwashing and diapering practices in day care centers.

PMID- 17021593
TI  - CDC's 60th anniversary. Director's perspective--William H. Foege, M.D., M.P.H.,
      1977-1983.
AB  - Modern public health began 210 years ago, in 1796, when Edward Jenner, using
      material from a cowpox lesion on the hand of Sarah Nelmes, vaccinated James
      Phipps. A later attempt to give Phipps smallpox demonstrated his immunity, and
      the vaccination era had begun. Although Jenner lacked our understanding of
      viruses, the immune system, or vaccinology, his clinical observations had
      convinced him that milkmaids were protected from smallpox because of their
      previous exposure to cowpox, and he acted to see if nature could be replicated.

PMID- 17021594
TI  - Monitoring progress toward achieving Maternal and Infant Healthy People 2010
      objectives--19 states, Pregnancy Risk Assessment Monitoring System (PRAMS), 2000
      2003.
AB  - PROBLEM/CONDITION: Certain modifiable maternal behaviors and experiences before,
      during, and after pregnancy are associated with adverse health outcomes for the
      mother and her infant (e.g., physical abuse, insufficient folic acid consumption,
      smoking during pregnancy, and improper infant sleep position). Information about
      these behaviors and experiences is needed to monitor trends in maternal and
      infant health, enhance understanding of the relation between maternal behaviors
      and infant health outcomes, plan and evaluate maternal and infant health
      programs, direct policy decisions, and monitor progress toward achieving the
      national Healthy People 2010 [HP 2010] objectives (US Department of Health and
      Human Services. Healthy people 2010. 2nd ed. With understanding and improving
      health and objectives for improving health [2 vols.]. Washington, DC: US
      Department of Health and Human Services; 2000). REPORTING PERIOD COVERED: 2000
      2003. DESCRIPTION OF SYSTEM: The Pregnancy Risk Assessment Monitoring System
      (PRAMS) is an ongoing, state- and population-based surveillance system designed
      to monitor selected maternal behaviors and experiences that occur before, during,
      and after pregnancy among women who deliver live-born infants. PRAMS employs a
      mixed mode data-collection methodology; up to three self-administered surveys are
      mailed to a sample of mothers; nonresponders are followed up with telephone
      interviews. Self-reported survey data are linked to selected birth certificate
      data and weighted for sample design, nonresponse, and noncoverage to create
      annual PRAMS analysis data sets that can be used to produce statewide estimates
      of perinatal health behaviors and experiences among women delivering live
      infants. This report summarizes data for 2000-2003 from 19 states (Alabama,
      Alaska, Arkansas, Colorado, Florida, Hawaii, Illinois, Louisiana, Maine,
      Nebraska, New Mexico, New York, North Carolina, Ohio, Oklahoma, South Carolina,
      Utah, Washington, and West Virginia) that measured progress toward achieving HP
      2010 objectives for eight perinatal indicators: 1) pregnancy intention, 2)
      multivitamin use, 3) physical abuse, 4) cigarette smoking during pregnancy, 5)
      cigarette smoking cessation, 6) drinking alcohol during pregnancy, 7)
      breastfeeding initiation, and 8) infant sleep position. RESULTS: In 2003,
      prevalence of intended pregnancy among women having a live birth ranged from
      48.1% in Louisiana to 66.5% in Maine; during 2000-2003, no state experienced a
      statistically significant (p< or =0.05) increase in prevalence of intended
      pregnancy, and one state experienced a significant decrease. In 2003, prevalence
      of multivitamin use at least four times per week during the month before
      pregnancy ranged from 23.0% in Arkansas to 45.2% in Maine; during 2000-2003,
      multivitamin use increased significantly in three states (Illinois, North
      Carolina, and Utah). In 2003, prevalence of physical abuse by a husband or
      partner during the 12 months before pregnancy ranged from 2.2% in Maine to 7.6%
      in New Mexico; during 2000-2003, significant decreases were recorded in three
      states (Alaska, Hawaii, and Nebraska). In 2003, prevalence of abstinence from
      cigarette smoking during the last 3 months of pregnancy ranged from 72.5% in West
      Virginia to 96.1% in Utah; during 2000-2003, a significant increase was recorded
      in Utah. In 2003, prevalence of smoking cessation during pregnancy ranged from
      30.2% in West Virginia to 65.8% in Utah; during 2000-2003, a significant increase
      was recorded in Utah. In 2003, prevalence of abstinence from alcohol during the
      last 3 months of pregnancy ranged from 91.3% in Colorado to 98.0% in Utah; during
      2000-2003, abstinence increased significantly in Louisiana and Utah but decreased
      significantly in Florida and Nebraska. In 2003, prevalence of mothers who
      breastfed their babies in the early postpartum period ranged from 51.2% in
      Louisiana to 90.3% in Alaska; during 2000-2003, significant increases were
      recorded in six states (Arkansas, Illinois, Louisiana, Nebraska, North Carolina,
      and South Carolina). In 2003, prevalence of healthy full-term infants who were
      placed to sleep on their backs ranged from 50.0% in Arkansas to 78.7% in
      Washington; during 2000-2003, significant increases were recorded in eight states
      (Alaska, Colorado, Illinois, Louisiana, Maine, Nebraska, North Carolina, and West
      Virginia). In 2003, all 19 states achieved or exceeded the HP 2010 objective for
      smoking cessation during pregnancy, and 16 states achieved the HP 2010 objective
      for abstinence from alcohol during the last 3 months of pregnancy. In addition,
      nearly half of the states achieved the objectives for breastfeeding in the early
      postpartum period and infant back sleep position. However, no state achieved the
      HP 2010 objectives for intended pregnancy, multivitamin use before pregnancy,
      absence of physical abuse before pregnancy, or abstinence from smoking during
      pregnancy. INTERPRETATION: PRAMS data indicate variability among states regarding
      progress toward achieving HP 2010 objectives in the area of maternal and child
      health. More progress has been made in achieving objectives focused on the period
      during and after pregnancy (e.g., smoking cessation and proper infant sleep
      position); less progress has been made in achieving objectives related to
      behaviors and experiences in the preconception period (e.g., pregnancy intention
      and multivitamin use). PUBLIC HEALTH ACTION: State maternal and child health
      programs can use these state- and population-based data to monitor progress
      toward achieving HP 2010 objectives, identify indicators to target for
      intervention, and plan and evaluate programs that promote positive maternal and
      infant health behaviors, experiences, and outcomes. These data also can be used
      to guide policy decisions that could affect the health of mothers and infants.

PMID- 17021595
TI  - Cardiorespiratory fitness and abdominal adiposity in youth.
AB  - The purpose of this study was to determine whether cardiorespiratory fitness
      (CRF) is associated with lower abdominal adiposity in youth. Subjects included
      healthy 61 African-American and 52 white children and adolescents (age: 8-17
      years). Body composition was measured by dual-energy X-ray absorptiometry and
      computed tomography. CRF (VO(2max)) was assessed using a graded maximal treadmill
      test. CRF was inversely related (P<0.05) to total adiposity, waist circumference,
      and visceral and abdominal subcutaneous adipose tissue (AT) independent of race.
      These findings remained significant (P<0.05) after adjusting for age, gender and
      pubertal status. Multiple regression analyses revealed that CRF is an independent
      contributor (P<0.05) of waist circumference, and visceral and abdominal
      subcutaneous AT after accounting for age, pubertal status, gender and body mass
      index percentile. Our observation suggest that in youth, CRF is associated with
      lower visceral and abdominal subcutaneous AT, and reinforces the notion that
      youth should engage in regular physical activity to improve aerobic fitness and
      reduce abdominal adiposity.

PMID- 17021596
TI  - Malnutrition among gynaecological cancer patients.
AB  - OBJECTIVE: To assess the nutritional status of patients with gynaecological
      cancer. DESIGN: A prospective study assessing the nutritional status of
      gynaecological patients with suspected or proven gynaecological cancer. SETTING:
      Queensland Centre for Gynaecological Cancer, Brisbane, Australia; a tertiary
      referral centre for gynaecological cancer. SUBJECTS: One hundred forty-five
      patients with suspected or proven gynaecological cancer aged 20-91 years.
      INTERVENTION: Scored patient-generated subjective global assessment (PG-SGA) and
      serum albumin before treatment. RESULTS: One hundred and sixteen (80%) patients
      were categorized as PG-SGA class A, 29 (20%) patients were PG-SGA B and none of
      the patients were PG-SGA C. Ovarian cancer patients had significantly lower serum
      albumin levels (P=0.003) and higher PG-SGA scores (P<0.001) than patients with
      other types of cancer and benign conditions. Sixty-seven per cent of patients
      with ovarian cancer were classified as PG-SGA B. After adjusting for patient's
      age, body mass index and albumin level, ovarian cancer patients were 19 times
      more likely to be categorized as PG-SGA class B compared to patients with benign
      conditions (95% confidence interval: 3.03-129.8; P=0.002). CONCLUSION:
      Malnutrition in gynaecological cancer patients is a significant problem,
      especially among those patients diagnosed with ovarian cancer.

PMID- 17021597
TI  - Breastfeeding practices and associated factors among children under 24 months of
      age in Timor-Leste.
AB  - OBJECTIVE: To describe breastfeeding practices and to assess the sociodemographic
      factors associated with selected breastfeeding indicators. DESIGN AND SETTING:
      The 2003 Demographic and Health Survey was a multi-stage cluster sample survey of
      4320 households from four different geographic areas in Timor-Leste. SUBJECTS: A
      total of 2162 children aged 0-23 months. RESULTS: A high proportion (97.6%) of
      infants had been ever breastfed, but only 46.1% had initiated breastfeeding
      within the first hour of birth. Seventy-eight percent of children <24 months were
      currently breastfed, 30.7% of infants <6 months were exclusively breastfed and
      12.5% of infants <12 months were bottle-fed. A high proportion of infants of 6-9
      months (82.0%) were receiving complementary food in addition to breast milk.
      Multivariate analysis revealed that exclusive breastfeeding was significantly
      lower in the rural west region (odds ratio (OR)=3.15) compared to the urban
      region, and among those from richest households (OR=1.90) compared to poorest.
      Mothers with primary education were significantly more likely to exclusively
      breastfeed than mothers with no education (OR=0.62). Increasing age of the infant
      was associated with significantly less current (OR=1.23) and exclusive (OR=1.35)
      breastfeeding. Continuation of breastfeeding at the end of the first year was
      significantly lower in non-working mothers (OR=1.58) compared to working mothers,
      and among infants born in health-care facilities (OR=2.16) than those born at
      home. CONCLUSIONS: Breastfeeding practices in Timor-Leste were satisfactory,
      except the exclusive breastfeeding at 6 months. However, more socioeconomically
      privileged groups demonstrated a poorer breastfeeding performance than
      disadvantaged groups. Further breastfeeding promotion programmes are needed
      across all population groups, and should include health-care providers and
      maternity institutions.

PMID- 17021598
TI  - Urinary excretion of equol by postmenopausal women consuming soymilk fermented by
      probiotic bifidobacteria.
AB  - OBJECTIVE: To study the effects of consuming isoflavone aglycone-enriched soymilk
      fermented by bifidobacteria on urinary excretion of equol with respect to
      fermentation, daidzein dose, supplementation duration and background diet.
      DESIGN: Double-blind crossover pilot study comprising three 14-day
      supplementation periods separated by a washout. SETTING: Victoria University,
      Melbourne, Australia. SUBJECTS: Sixteen postmenopausal women. INTERVENTION:
      SUBJECTS randomized into two groups consuming either fermented (FS) or non
      fermented soymilk (NFS), ingested three daily dosages of daidzein via soymilk and
      collected pooled urine specimens. Daidzein and equol were quantified using high
      performance liquid chromatography. RESULTS: After 14-days supplementation six
      women (38%) excreted equol (>1 micromol equol/day), including four from the FS
      group, two of whom were classified as non-producers at day 4. Bifidobacteria
      ingestion, composition of daidzein and its glucosides, and carbohydrate intake
      appeared to influence equol formation among equol producers. CONCLUSIONS: Pilot
      study group mean urinary equol excretion results provided insufficient evidence
      (P>0.05) that FS consumption instigates equol production in women predetermined
      as non-producers.

PMID- 17021599
TI  - The altered fluid distribution in obesity may reflect plasma hypertonicity.
AB  - OBJECTIVE: This study explored whether the increased extracellular relative to
      intracellular fluid (ECF/ICF) ratio in obesity might reflect osmotic effects of
      elevated plasma solute concentrations. DESIGN: Cross-sectional, epidemiological
      survey. SETTING AND SUBJECTS: The present analysis used nationally representative
      data from the Third National Health and Nutrition Examination Survey on community
      dwelling adults (aged 40-59 years) in the US without evidence of glucose
      dysregulation or chronic disease (n=1285). INTERVENTION: Body mass index (BMI)
      was estimated from measured height and weight. Total body reactance, an index of
      body fluid distribution, was determined by bioelectrical impedance analysis.
      Plasma tonicity (the cumulative index of osmotically effective plasma solute) was
      estimated from plasma glucose, sodium and potassium. Sex-specific relative odds
      of lower reactance (<or=50 Omega/m for women, <or=40 Omega/m for men) and plasma
      hypertonicity (tonicity >or=295 mmol/l) associated with overweight (25<or=BMI
      <30) and obesity (BMI>or=30) were estimated using logistic regression models that
      controlled for sociodemographic variables, smoking, leisure-time physical
      activity, total energy intake, serum creatinine, plasma insulin and glucose.
      Multinomial logistic regression models tested for associations between weight
      status and specific serum solute. RESULTS: Independent of covariates, in men and
      women, overweight and obesity were associated with increased odds of lower
      reactance and hypertonicity. Overweight and obese individuals with lower
      reactance had significantly higher serum sodium than normal weight individuals.
      CONCLUSIONS: Elevated plasma solute concentrations are associated with obesity in
      free-living adults. Physicians and researchers should be alert to a possible link
      between hypertonicity and obesity. SPONSORSHIP: Grants from the NIH, Nestle
      Waters.

PMID- 17021600
TI  - ELMO1 increases expression of extracellular matrix proteins and inhibits cell
      adhesion to ECMs.
AB  - We have previously identified the engulfment and cell motility 1 (ELMO1) as a
      susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in
      the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in
      the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus
      anti-Thy1.1 antibody [E30] injection). We found that the expression of the Elmo1
      was significantly increased in the renal cortex and glomeruli of
      uninephrectomized rats injected with E30 compared to controls. By in situ
      hybridization, the expression of Elmo1 was shown to be elevated in the diseased
      kidney, especially in glomerular epithelial cells. In COS cells, the
      overexpression of ELMO1 resulted in a substantial increase in fibronectin
      expression, whereas the depletion of the ELMO1 by small interfering RNA (siRNA)
      targeting ELMO1 significantly suppressed the fibronectin expression in ELMO1
      overexpressing and control cells. We also found that the expression of integrin
      linked kinase (ILK) was significantly increased in ELMO1 overexpressing cells,
      and the ELMO1-induced increase in fibronectin was partially, but significantly,
      inhibited by siRNA targeting ILK. Furthermore, we identified that the cell
      adhesion to ECMs was considerably inhibited in cells overexpressing ELMO1. These
      results suggest that the ELMO1 contributes to the development and progression of
      chronic glomerular injury through the dysregulation of ECM metabolism and the
      reduction in cell adhesive properties to ECMs.

PMID- 17021601
TI  - Genome-wide scan for type 1 diabetic nephropathy in the Finnish population
      reveals suggestive linkage to a single locus on chromosome 3q.
AB  - Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in
      patients with type 1 as well as type 2 diabetes, and accounts for 40% of end
      stage renal disease in the Western world. Familial clustering of DN suggests
      importance of genetic factors in the development of the disease. In the present
      study, we performed a two-stage genome-wide scan to search for chromosomal loci
      containing susceptibility genes for nephropathy in patients with type 1 diabetes.
      In total, 83 discordant sib pairs (DSPs), sibs concordant for type 1 diabetes but
      discordant for nephropathy, were collected from Finland, a homogeneous population
      with one of the highest incidences of type 1 diabetes. To map loci for DN, we
      applied DSP analysis to detect linkage. In the initial scan, 73 DSPs were typed
      using 900 markers with an average intermarker distance of approximately 4 cM.
      Multipoint DSP analysis identified five chromosome regions (3q, 4p, 9q, 16q, and
      22p) with maximum logarithm of odds (LOD) score (MLS) >or=1.0 (corresponding to a
      nominal P-value <or=0.015). In the second stage, additional 43 markers flanking
      these five loci were genotyped in all 83 DSPs. Using simulations, we determined
      the empirical threshold with LOD score of 1.76 and 3.12 for suggestive and
      significant linkage, respectively. No locus reached the genome-wide significance
      of 5%. However, one locus on 3q reached suggestive linkage with MLS of 2.67
      (P=4.4 x 10(-4)). These results, together with data from others, suggest that the
      locus on 3q most likely has a susceptibility gene for DN.

PMID- 17021602
TI  - Hepatitis B treatment: Lessons for the nephrologist.
AB  - Hepatitis B affects approximately 350 million people worldwide, and an estimated
      1.25 million people in the United States. Although most people infected with the
      virus do not develop significant hepatic disease from hepatitis B, 15-40% will
      develop serious complications. These complications include cirrhosis, the
      development of hepatocellular carcinoma , and hepatic decompensation. Patients
      with renal failure have increased risk of acquiring the virus through blood
      transfusions and contact with bodily fluids at hemodialysis centers, and of
      developing complications from hepatitis B virus infection. Renal transplant
      patients are at increased risk for exacerbations of hepatitis B with
      immunosuppression. Thus, it is crucial for the nephrologist to have a clear
      understanding of the natural history and treatment of hepatitis B, both pre- and
      post-renal transplant.

PMID- 17021603
TI  - Hydroxyproline ingestion and urinary oxalate and glycolate excretion.
AB  - Endogenous synthesis of oxalate is an important contributor to calcium oxalate
      stone formation and renal impairment associated with primary hyperoxaluria.
      Although the principal precursor of oxalate is believed to be glyoxylate,
      pathways in humans resulting in glyoxylate synthesis are not well defined.
      Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate
      precursor. We have investigated the contribution of dietary hydroxyproline
      derived from gelatin to urinary oxalate and glycolate excretion. Responses to the
      ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate
      diets. The time course of metabolism of a 10 g gelatin load was determined as
      well as the response to varying gelatin loads. Urinary glycolate excretion was
      5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate
      excretion was 43% higher. Significant changes in plasma hydroxyproline and
      urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but
      not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen
      turnover and hydroxyproline intake suggests that hydroxyproline metabolism
      contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate
      derived from endogenous synthesis. Our results also revealed that the kidney
      absorbs significant quantities of hydroxyproline and glycolate, and their
      metabolism to oxalate in this tissue warrants further consideration.

PMID- 17021604
TI  - Regulation of kidney acid excretion by endothelins.
AB  - Endothelin (ET) is a potent vasoconstrictor that is now known to modulate kidney
      tubule transport, including kidney tubule acidification. Animals undergoing an
      acid challenge to systemic acid-base status and with some models of chronic
      metabolic acidosis have increased kidney ET production. Increased ET
      production/activity contributes to enhanced kidney tubule acidification that
      facilitates kidney acid excretion in response to an acid challenge to systemic
      acid-base status. The data to date support a physiologic role for ET in mediating
      enhanced kidney acidification in response to acid challenges, but do not support
      an ET role in maintaining kidney tubule acidification in control, non-acid
      challenged states. ET increases acidification in both the proximal and distal
      nephron and appears to exert its effects both directly and indirectly, the latter
      through modulating the levels and/or activity or other mediators of kidney tubule
      acidification. ET also contributes to enhanced kidney acidification in some
      pathophysiologic states and might contribute to some untoward outcomes associated
      with these conditions. Whether ET should be a therapeutic target in treating
      and/or preventing some of these untoward outcomes remains an open question. This
      review supports continued research into the physiologic and possibly
      pathophysiologic role of ET in settings of increased kidney tubule acidification.

PMID- 17021605
TI  - Cellular focal segmental glomerulosclerosis: Clinical and pathologic features.
AB  - Five pathologic variants of idiopathic focal segmental glomerulosclerosis (FSGS)
      are recognized: collapsing (COLL), cellular (CELL), glomerular tip lesion (GTL),
      perihilar, and not otherwise specified (NOS). The prognostic significance of CELL
      FSGS has not been determined. We compared the presenting clinical and pathologic
      characteristics in 225 patients with CELL (N=22), COLL (N=56), GTL (N=60), and
      NOS (N=87) variants of idiopathic FSGS. CELL, COLL, and tip lesion all showed
      greater frequency and severity of nephrotic syndrome, and shorter time to biopsy
      compared to NOS. Predictors of end-stage renal disease (ESRD) for all FSGS
      patients included initial serum creatinine, % global sclerosis, % COLL lesions,
      chronic tubulo-interstitial injury score, and lack of remission response. COLL
      FSGS had the highest rate of renal insufficiency at presentation, most extensive
      glomerular involvement and chronic tubulo-interstitial disease, fewest remissions
      (13.2%), and highest rate of ESRD (65.3%). GTL patients were older and showed the
      highest remission rate (75.8%) and lowest rate of ESRD (5.7%). CELL variant
      showed intermediate rates of remission (44.5%) and ESRD (27.8%) compared to COLL
      and tip lesion. CELL variant may include cases of unsampled tip or COLL lesion,
      underscoring the importance of adequate sampling. Our data support the view that
      CELL and COLL FSGS are not equivalent and validates an approach to pathologic
      classification that distinguishes between COLL, CELL, and tip lesion variants of
      FSGS.

PMID- 17021606
TI  - Estradiol increases proteinuria and angiotensin II type 1 receptor in kidneys of
      rats receiving L-NAME and angiotensin II.
AB  - Prospective, placebo-controlled clinical trials suggest that estrogen may have
      adverse effects on the vascular system in women. The goal of this study was to
      determine if 17beta-estradiol (E2) would have adverse effects on the
      renovasculature in a rat model of renal injury characterized by low nitric oxide
      (NO) and high angiotensin II (AngII). We studied female Wistar rats that were
      sham-operated (sham), ovariectomized (OVX), or ovariectomized and replaced with
      E2 (OVX/E2). All rats were maintained on a high salt diet and renovascular injury
      was caused by treating rats with an inhibitor of NO synthase, N(omega)-nitro-L
      arginine-methyl-ester (L-NAME), for 14 days, plus AngII on days 11 through 14. L
      NAME/AngII treatment, as compared to placebo, caused proteinuria, glomerular
      injury, and fibrinoid necrosis of renal arterioles in sham-operated rats.
      Ovariectomy reduced L-NAME/AngII-induced renal damage, whereas E2 treatment
      increased L-NAME/AngII-induced damage in OVX rats. In rats treated with L
      NAME/AngII, levels of AngII type 1 receptor (AT(1)R) protein were higher in the
      renal cortex of sham and OVX/E2 rats than in OVX rats. AT(1)R protein correlated
      with renal injury. E2 treatment also increased expression of AT(1)R mRNA. Thus,
      under conditions of low NO and high AngII, E2 exacerbated renal injury. E2
      mediated increases in renal cortical AT(1)R expression may represent a novel
      mechanism for the adverse renovascular effects of estrogen.

PMID- 17021607
TI  - Metabolic consequences of body size and body composition in hemodialysis
      patients.
AB  - Small body mass index is associated with increased mortality in chronic
      hemodialysis patients. The reasons for this observation are unclear but may be
      related to body composition. This study aimed to investigate the body composition
      in chronic hemodialysis patients. The difference between body mass and the sum of
      muscle, bone, subcutaneous, and visceral adipose tissue masses, measured by whole
      body magnetic resonance imaging, was defined as the high metabolic rate
      compartment representing the visceral mass. Protein catabolic rate was calculated
      from urea kinetics. Forty chronic hemodialysis patients (mean age 54.7 years;
      87.5% African Americans; 45% females) were studied. High metabolic rate
      compartment expressed in percent of body weight was inversely related to body
      weight (r=-0.475; P=0.002) and body mass index (r=-0.530; P<0.001). In a multiple
      linear regression model, protein catabolic rate was significantly correlated only
      with high metabolic rate compartment (r=0.616; P<0.001). Assuming that protein
      catabolic rate in addition to protein intake reflects urea and uremic toxin
      generation, it follows that high metabolic rate compartment is the major
      compartment involved in their generation. Consequently, uremic toxin production
      rate may be relatively higher in patients with low body weight and low body mass
      index as compared to their heavier counterparts. The poorer survival observed in
      smaller dialysis patients may be related to these relative differences.

PMID- 17021608
TI  - Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for
      detecting acute kidney injury.
AB  - Urinary exosomes containing apical membrane and intracellular fluid are normally
      secreted into the urine from all nephron segments, and may carry protein markers
      of renal dysfunction and structural injury. We aimed to discover biomarkers in
      urinary exosomes to detect acute kidney injury (AKI), which has a high mortality
      and morbidity. Animals were injected with cisplatin. Urinary exosomes were
      isolated by differential centrifugation. Protein changes were evaluated by two
      dimensional difference in gel electrophoresis and changed proteins were
      identified by mass spectrometry. The identified candidate biomarkers were
      validated by Western blotting in individual urine samples from rats subjected to
      cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion;
      and intensive care unit (ICU) patients with and without AKI. We identified 18
      proteins that were increased and nine proteins that were decreased 8 h after
      cisplatin injection. Most of the candidates could not be validated by Western
      blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before
      serum creatinine increase and tubule damage) and remained elevated 51.5-fold at
      day 5 (peak renal injury) after cisplatin injection. By immunoelectron microscopy
      and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin
      A was increased 31.6-fold in the early phase (2-8 h) of I/R, but not in prerenal
      azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI
      compared to the patients without AKI. We conclude that (1) proteomic analysis of
      urinary exosomes can provide biomarker candidates for the diagnosis of AKI and
      (2) urinary Fetuin-A might be a predictive biomarker of structural renal injury.

PMID- 17021610
TI  - Beta blockers in the management of chronic kidney disease.
AB  - The sympathetic nervous system modulates renal function through its receptors
      namely beta1 (cardiac output and renin release), alpha1 (systemic and
      renovascular constriction), and beta2 renovascular dilation. Sympathetic
      overactivity is commonly seen in chronic kidney disease (CKD) and is an important
      contributor to increasing the risk of cardiovascular events as well as increasing
      renal disease progression. Recent evaluations of drug use in people with CKD
      shows a remarkably low percentage of patients receiving beta-blockers, especially
      in more advanced stage CKD when cardiovascular risk is higher. This is in large
      part due to tolerability of these agents. Moreover, water-soluble beta-blockers
      such as atenolol and metoprolol are dialyzable and require supplementation to
      avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta
      blockers have better tolerability and different effects on renal hemodynamics as
      well as metabolic variables. These effects are related to the relative alpha1
      blocking effect of agents such as carvedilol and labetolol, with carvedilol
      having relatively greater alpha-blocking effects. Few studies evaluate beta
      blockers on cardiovascular risk in CKD patients. Studies with carvedilol
      demonstrate attenuated increases in albuminuria as well as reduction in
      cardiovascular events in CKD patients with hypertension. This paper reviews the
      animal and clinical trial data that evaluate beta-blockers in CKD highlighting
      the vasodilating beta-blockers. It is apparent that greater use of this drug
      class for blood pressure control would further enhance reduction of risk of heart
      failure, the most common cause of death in the first year of starting dialysis.

PMID- 17021609
TI  - Mortality risk among hemodialysis patients receiving different vitamin D analogs.
AB  - Intravenous vitamin D is standard therapy for secondary hyperparathyroidism in
      hemodialysis (HD) patients. In for-profit dialysis clinics, mortality was higher
      for patients on calcitriol compared to paricalcitol. Doxercalciferol, a second
      vitamin D2 analog, is currently available. We assessed mortality associated with
      each vitamin D analog and with lack of vitamin D therapy in patients who began HD
      at Dialysis Clinic Inc. (DCI), a not-for-profit dialysis provider. During the
      1999-2004 study period we studied 7731 patients (calcitriol: n=3212;
      paricalcitol: n=2087; doxercalciferol: n=2432). Median follow-up was 37 weeks.
      Mortality rates (deaths/100 patient-years) were identical in patients on
      doxercalciferol (15.4, 95% confidence interval (13.6-17.1)) and paricalcitol
      (15.3 (13.6-16.9)) and higher in patients on calcitriol (19.6 (18.2-21.1))
      (P<0.0001). In all models mortality was similar for paricalcitol versus
      doxercalciferol (hazard ratios=1.0). In unadjusted models, mortality was lower in
      patients on doxercalciferol (0.80 (0.66, 0.96)) and paricalcitol (0.79 (0.68,
      0.92)) versus calcitriol (P<0.05). In adjusted models, this difference was not
      statistically significant. In all models mortality was higher for patients who
      did not receive vitamin D versus those who did (1.2 (1.1-1.3)). Mortality in
      doxercalciferol- and paricalcitol-treated patients was virtually identical.
      Differences in survival between vitamin D2 and D3 may be smaller than previously
      reported.

PMID- 17021611
TI  - Symptoms of depression, prescription of benzodiazepines, and the risk of death in
      hemodialysis patients in Japan.
AB  - Many hemodialysis patients in Japan have symptoms of depression, but whether
      those patients are treated appropriately is unknown. As part of the Dialysis
      Outcomes and Practice Patterns Study, data on symptoms of depression, physician
      diagnosed depression, prescribed medications, and death were collected
      prospectively in cohorts in Japan (n=1603) and 11 other countries (n=5872).
      Symptoms of depression were as prevalent in Japan as elsewhere, but in Japan a
      much smaller percentage of patients had physician-diagnosed depression: only 2%
      in Japan vs 17% elsewhere. Antidepressants were much less commonly prescribed in
      Japan: only 1% in Japan vs 17% elsewhere for patients with many and frequent
      symptoms of depression, and 16% in Japan vs 34% elsewhere for patients with
      physician-diagnosed depression. In Japan, symptoms of depression were associated
      with prescription of benzodiazepines (without antidepressants), and patients with
      physician-diagnosed depression were twice as likely to be given benzodiazepines:
      32% in Japan vs 16% elsewhere. Benzodiazepine monotherapy was associated with
      death (relative risk 1.56, 95% confidence interval (CI), 1.25-1.94), even after
      adjustments for 13 likely confounders (relative risk 1.27, 95% CI, 1.01-1.59).
      Hemodialysis patients in Japan with symptoms of depression are given not
      antidepressants but benzodiazepines, a practice associated with higher mortality.

PMID- 17021612
TI  - Biometrical genetic analysis of luteovirus transmission in the aphid Schizaphis
      graminum.
AB  - The aphid Schizaphis graminum is an important vector of the viruses that cause
      barley yellow dwarf disease. We studied the genetic architecture of virus
      transmission by crossing a vector and a non-vector genotype of S. graminum. F1
      and F2 hybrids were generated, and a modified line-cross biometrical analysis was
      performed on transmission phenotype of two of the viruses that cause barley
      yellow dwarf: Cereal yellow dwarf virus (CYDV)-RPV and Barley yellow dwarf virus
      (BYDV)-SGV. Our aims were to (1) determine to what extent differences in
      transmission ability between vectors and non-vectors is due to net additive or
      non-additive gene action, (2) estimate the number of loci that determine
      transmission ability and (3) examine the nature of genetic correlations between
      transmission of CYDV-RPV and BYDV-SGV. Only additive effects contributed
      significantly to divergence in transmission of both CYDV-RPV and BYDV-SGV. For
      each luteovirus, Castle-Wright's estimator for the number of effective factors
      segregating for transmission phenotype was less than one. Transmission of CYDV
      RPV and BYDV-SGV was significantly correlated in the F2 generation, suggesting
      that there is a partial genetic overlap for transmission of these luteoviruses.
      Yet, 63% of the F2 genotypes transmitted CYDV-RPV and BYDV-SGV at significantly
      different rates. Our data suggest that in S. graminum, the transmission
      efficiency of both CYDV-RPV and BYDV-SGV is regulated by a major gene or set of
      tightly linked genes, and the transmission efficiency of each virus is influenced
      by a unique set of minor genes.

PMID- 17021613
TI  - Mendelian segregation for two-factor apomixis in Erigeron annuus (Asteraceae).
AB  - The inheritance of asexual seed development (apomixis) in Erigeron annuus
      (Asteraceae) was evaluated in a triploid (2n=3x=27) population resulting from a
      cross between an apomictic tetraploid (2n=4x=36) pollen parent and a sexual
      diploid (2n=2x=18) seed parent. Diplospory (unreduced female gametophyte
      formation) and autonomous development (embryo and endosperm together) segregated
      independently in the population yielding four distinct phenotype classes: (1)
      apomictic plants combining diplospory and autonomous development, (2)
      diplosporous plants lacking autonomous development, (3) meiotic plants with
      autonomous (though abortive) development and (4) meiotic plants lacking
      autonomous development. Each class was represented by approximately one-quarter
      of the population (n=117), thus corresponding to a two-factor genetic model with
      no linkage (chi(2)=2.59, P=0.11). Observations demonstrate that autonomous embryo
      and endosperm development (jointly) may occur in either reduced or unreduced egg
      cells. The cosegregation of the traits is attributed to tight linkage or
      pleiotropy. The data are consistent with the hypothesis that autonomous
      development in E. annuus is regulated by a single fertilization factor, F, which
      initiates development of both the embryo and the endosperm in the absence of
      fertilization.

PMID- 17021614
TI  - Antagonistic pleiotropy may help population-level selection in maintaining
      genetic polymorphism for transmission rate in a model phytopathogenic fungus.
AB  - It has been shown theoretically that the conditions for the maintenance of
      polymorphism at pleiotropic loci with antagonistic effects on fitness components
      are rather restrictive. Here, we use a metapopulation model to investigate
      whether antagonistic pleiotropy could help maintain polymorphism involving common
      deleterious alleles in the phytopathogenic fungus Microbotryum violaceum. This
      fungus causes anther smut disease of the Caryophyllaceae. A previous model has
      shown that the sex-linked deleterious alleles can be maintained under a
      metapopulation structure, when intra-tetrad selfing (mating between products of
      the same meiosis) is high, due to founder effects and selection at the population
      level. Here, we add two types of pleiotropic advantages to the metapopulation
      model. A competitive advantage for strains carrying the sex-linked deleterious
      alleles did not facilitate their maintenance because competitive situations were
      too rare. In contrast, higher spore production did facilitate the maintenance of
      the deleterious alleles at low intra-tetrad mating rates and with a large
      advantage for spore production. These results show that antagonistic pleiotropy
      may promote the persistence of genetic variation, in combination with other
      selective forces.

PMID- 17021615
TI  - Evolution of allelic dimorphism in malarial surface antigens.
AB  - The extensive sequence variation in most surface antigens of Plasmodium
      falciparum is one of the major factors why clinical immunity to malaria develops
      only after repeated infections with the same species over several years. For some
      P. falciparum surface antigens, all observed alleles clearly fall into two
      allelic classes, with divergence between classes dwarfing divergence within
      classes. We discuss the ways in which such allelic dimorphism deviates from the
      expected shape of the genealogy of genes under either neutral evolution or
      standard balancing selection, and present a simple test, based on coalescent
      theory, to detect this deviation in samples of DNA sequences. We review previous
      hypotheses for the origin and evolution of allelic dimorphism in malarial
      antigens and discuss the difficulties of explaining the available data under
      these proposals. We conclude by offering several possible classes of explanations
      for allelic dimorphism, which are worthy of further theoretical and empirical
      exploration.

PMID- 17021617
TI  - Antibiotic blocks mRNA path on the ribosome.

PMID- 17021618
TI  - CUT it out: silencing of noise in the transcriptome.

PMID- 17021619
TI  - Transmembrane signaling by asymmetry.

PMID- 17021621
TI  - Convergent evolution of clamp-like binding sites in diverse chaperones.
AB  - Molecular chaperones have evolved diverse tertiary and quaternary structures to
      stabilize non-native polypeptides and facilitate their transition to the native
      state. Indeed, different families of chaperones lack sequence similarity, and few
      are represented ubiquitously in all three domains of life. Despite their discrete
      evolutionary paths, recent crystal structures reveal that many chaperones use
      seemingly convergent strategies to bind non-native proteins. This
      crystallographic evidence shows, or strongly suggests, that chaperones including
      prefoldin, Skp, trigger factor, Hsp40 and Hsp90 have clamp-like structural
      features used to grip substrate proteins. We explore the notion that clamp-like
      structures are evolutionarily favored by both ATP-dependent and ATP-independent
      molecular chaperones. Presumably, clamps present a multivalent binding surface
      ideal for protecting unstable protein conformers until they reach the native
      state or are transferred to another component of the folding machinery.

PMID- 17021622
TI  - Fused radioimmunoscintigraphy for treatment planning.
AB  - Advances in imaging technologies, including computerized tomography (CT) and
      single-photon emission tomography (SPECT), are improving the role of imaging in
      prostate cancer diagnosis and treatment. Hybrid (SPECT/CT) imaging, in
      particular, shows an increased sensitivity for identification of prostate cancer.
      Published studies have also recently proposed a new paradigm in the
      administration of radiation therapy for prostate cancer, favoring dose-escalation
      strategies to improve tumor control for localized disease. Conventional dose
      escalation protocols have previously relied primarily on margin extension to the
      entire prostate gland to achieve dose-escalation; extending increased risk to
      radiosensitive normal structures. A newer strategy proposes use of advanced
      imaging to confine dose-escalation to biological target volumes identified on
      capromab pendetide SPECT/CT -fused image sets or image-guided radiation therapy
      (IGRT). This strategy defines a shift in radiation dosimetry and planning from
      uniform glandular prescription dosing with dose-escalation applied generically to
      the peripheral regions and margin extension; to dose-escalation confinement to
      discrete regions of known disease as defined by focal uptake on
      radioimmunoscintigraphy fusion with anatomic image sets, with minimal margin
      extension. The introduction of advanced imaging for IGRT in prostate cancer has
      also introduced an improved capability for the early-identification of patients
      at risk for metastatic disease, where more aggressive therapeutic interventions
      may prove beneficial.

PMID- 17021623
TI  - The emergence of radioimmunoscintigraphy for prostate cancer.
AB  - The ability to label tissue-specific antibodies has long been of interest for
      improving detection and guidance for therapeutic applications. The most studied
      target for prostate cancer is the prostate-specific membrane antigen, which is
      upregulated in prostate cancer, hormone-refractive disease, and prostate cancer
      metastases. Investigations using radioimmunoscintigraphy with the radiolabeled
      7E11 antibody capromab pendetide have significantly improved sensitivity for
      prostate cancer detection compared with standard cross-sectional imaging, based
      on tissue confirmation of pathologic results. Over the past 5 years,
      significantly greater image resolution from improved camera technology and the
      use of co-registration to fuse functional and anatomic (computerized tomography
      and magnetic resonance imaging) images have dramatically enhanced prostate cancer
      localization. Outcomes data from several sources have spurred a resurgence in
      interest in this imaging modality.

PMID- 17021624
TI  - Contrast-enhanced ultrasound imaging of prostate cancer.
AB  - Ultrasound imaging of the prostate is commonly used to assess the size of the
      gland and for needle placement during systematic biopsy. Ultrasound evaluation of
      prostate cancer is limited by difficulty in distinguishing benign from malignant
      tissue. Although Doppler techniques may provide some improvement in the detection
      of prostate cancer, targeted biopsy based on conventional ultrasound with Doppler
      is not sufficient to replace systematic biopsy. Contrast-enhanced ultrasound
      imaging techniques that employ microbubble contrast agents represent an
      innovative approach to imaging of the neovascularity associated with prostate
      cancer. This review describes the application of contrast-enhanced ultrasound to
      improve detection and assessment of prostate cancer.

PMID- 17021625
TI  - Magnetic resonance imaging and spectroscopy of prostate cancer.
AB  - Magnetic resonance imaging may improve the staging of prostate cancer compared
      with clinical evaluation alone, computerized tomography, or transrectal
      ultrasound, and it allows simultaneous and detailed evaluation of prostatic,
      periprostatic, and pelvic anatomy. Endorectal magnetic resonance imaging and
      magnetic resonance spectroscopic imaging (endoMRI/MRSI) allow better
      visualization of the zonal anatomy of the prostate and better delineation of
      tumor location, volume, and extent (stage). Metabolic criteria used to identify
      and localize prostate cancer with endoMRI/MRSI have been standardized, thus
      improving the accuracy of the examination and limiting interobserver variations
      in interpretation. Evidence is now emerging that endoMRI/MRSI may also be helpful
      in assessing response to prostate cancer treatment, most commonly with radiation
      and/or androgen-deprivation therapy.

PMID- 17021626
TI  - Erectile function outcomes in the current era of anatomic nerve-sparing radical
      prostatectomy.
AB  - The contemporary use of anatomic nerve-sparing radical prostatectomy, which
      entails preserving the autonomic nerve supply to the penis required for penile
      erection, has led to improved erectile function outcomes compared with what has
      been seen historically. However, delay of postoperative recovery of erection for
      as long as 2 years is common, such that dysfunctional erection status lingers as
      a major postoperative problem. Several possible strategies to improve overall
      recovery rates and to hasten postoperative recovery of erectile function are
      currently being advanced. These include pharmacologic rehabilitation therapy and
      neuromodulatory therapy. Rigorous basic scientific investigation and clinical
      assessment of these new strategic approaches are critically important to
      establish their actual therapeutic benefits.

PMID- 17021627
TI  - Pathologic guidelines for orthotopic urinary diversion in women with bladder
      cancer: a review of the literature.
AB  - Orthotopic lower urinary tract reconstruction to the native intact urethra
      following radical cystectomy for bladder cancer was slower to gain clinical
      acceptance for women than for men. Until the 1990s, little was known about the
      natural history of urethral involvement by urothelial carcinoma in women with
      primary bladder cancer. The increasing availability of pathologic data to define
      the incidence of and risks for urethral involvement in women sparked an
      increasing interest in orthotopic diversion in female patients. Pathologic
      guidelines have been suggested to identify women suitable for orthotopic
      diversion. Preoperative involvement of the bladder neck is a significant risk
      factor for secondary tumor of the urethra, but is not an absolute
      contraindication, as long as full-thickness, intraoperative frozen-section
      analysis demonstrates no tumor involvement of the proximal urethra. Although less
      common, anterior vaginal wall tumor involvement may be a significant risk factor
      for urethral tumor involvement. Other pathologic parameters, including tumor
      multifocality, carcinoma in situ of the bladder, and tumor grade and stage, do
      not seem to be absolute contraindications. Long-term follow-up is critical for
      all patients. Women undergoing orthotopic reconstruction, if appropriately
      selected, should be assured of an oncologically sound operation and good function
      with their neobladder.

PMID- 17021628
TI  - Treatment of upper tract urothelial carcinoma: a review of surgical and adjuvant
      therapy.
AB  - Upper tract urothelial carcinoma is a disease entity that has not been as
      extensively studied and reviewed as carcinoma of the bladder. Recent advances in
      technology and adjuvant therapy have changed the treatment armamentarium of
      oncologists and urologists. A literature review was conducted that focused on
      newer surgical techniques, including laparoscopy and endoscopic management of
      upper tract disease. Adjuvant therapy including immunotherapy, chemotherapy, and
      radiation is also reviewed. Nephroureterectomy with removal of a bladder cuff
      still remains the gold standard of treatment. However, laparoscopic
      nephroureterectomy is quickly becoming popular, with equivalent recurrence rates.
      Because of the relatively recent introduction of laparoscopy into the urologic
      field, long-term data with respect to recurrence rates and survival rates are not
      yet available. Immunotherapy has also shown promise, but with higher recurrence
      rates than surgery. Chemotherapy and radiation also show some improvement in
      recurrence rates, but there have been no randomized, prospective trials.
      Endoscopic management is acceptable in patients with severe medical comorbidities
      or solitary kidneys but requires rigorous and close follow-up. Adjuvant therapy
      with either chemotherapy or radiation is still debated but does offer some
      improvement in disease-specific survival. Randomized, prospective, placebo
      controlled studies are required but are difficult to perform because of the
      relatively low incidence and prevalence of this disease.

PMID- 17021629
TI  - The business of urology-your first job.
AB  - Young doctors nearing the end of their residency must begin to consider how to
      chart the course of their careers. Most residents will go into private practice.
      This requires a huge leap, from academia into the business world of medicine.
      Young doctors, long preoccupied with the clinical and academic aspects of
      medicine, are frequently ill-prepared for this process, having no insight as to
      what they can do to match themselves to the right practice or multi-specialty
      group. This article discusses the stages of this process, from initial geographic
      decisions to securing interviews, to assessing the health of a given practice, to
      the details of contract negotiation.

PMID- 17021630
TI  - A gathering of urologists and urogynecologists in montreal: a report from the
      35th annual meeting of the international continence society, august 28-september
      2, 2005, montreal, quebec, Canada.

PMID- 17021631
TI  - Endourology: a basic science and clinical update: highlights from the 23rd world
      congress on endourology and the shockwave lithotripsy 21st basic research
      symposium, august 23-26, 2005, amsterdam, the Netherlands.

PMID- 17021632
TI  - Sperm health in the aging male.

PMID- 17021633
TI  - Enhancement of sperm motility in assisted reproduction.

PMID- 17021634
TI  - Translation research in prostate cancer.

PMID- 17021635
TI  - Is estrogen for urinary incontinence good or bad?

PMID- 17021636
TI  - What is the Effect of Overactive Bladder Medication on Sleep?

PMID- 17021637
TI  - Treatment of localized prostate cancer.
AB  - This article provides an overview of treatment of localized prostate cancer,
      which was discussed in detail in the second scientific session of the 16th
      International Prostate Cancer Update. The role of radical prostatectomy in
      localized disease was presented by Bob Djavan, MD. Benefits and risks of radical
      prostatectomy were addressed by Gerald Chodak, MD. Robert E. Donohue, MD,
      presented the role of radical prostatectomy in Gleason grade 8, 9, and 10 tumors.
      Impact of positive margins on outcomes after radical prostatectomy was presented
      by James A. Eastham, MD. E. David Crawford, MD, provided an overview of the role
      of targeted therapy. Indications and results of brachytherapy were presented by
      Mack Roach, III, MD. Finally, Michael J. Manyak, MD, described the evolution of
      radioimmunoscintigraphy and clinical outcomes data.

PMID- 17021638
TI  - New techniques and management options for localized prostate cancer.
AB  - Prostate cancer is diagnosed in younger men who want treatment that does not
      compromise their quality of life, take time away from work, or cause worrisome
      side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic
      radical prostatectomy, and third-generation cryotherapy are modifications of
      previously used techniques in the treatment of prostate cancer and are presented
      in this article. Although some or all of the outcomes might be expected to change
      in the future, the urologic surgeon is left to select an approach, presumably on
      the basis of the experience, level of training, and care pathways at his or her
      institution.

PMID- 17021639
TI  - Prostate cancer: epidemiology, screening, and biomarkers.
AB  - Carcinoma of the prostate continues to be a major health problem in the United
      States. Beginning in 1988, a marked increase in detection of prostate cancer
      occurred due to the development of a test for prostate-specific antigen (PSA).
      Controversy exists, however, about the value of PSA as a tumor marker. Although
      it has prognostic significance both before and after definitive therapy for
      prostate cancer, it is unclear whether routine PSA screening will translate into
      a survival advantage for patients. Because of its limitations, PSA may not
      ultimately be a good enough marker to be used as a screening tool. However,
      molecular biology has led to a rapid rise in the number of potential new prostate
      tumor markers, which may eventually overcome the weaknesses of PSA. Considerable
      progress has occurred in the diagnosis and management of prostate cancer: more is
      understood about the risk factors for the disease, possible ways to prevent it,
      and new ways to diagnose and monitor it. These developments have already
      translated into better patient care, while also identifying where further
      improvements are needed.

PMID- 17021640
TI  - Monitoring response, prediction methodology, staging, and imaging in prostate
      cancer.
AB  - The predictive values of various tests and examinations are assessed as they
      relate to prostate cancer progression and treatment. The usefulness of post
      treatment biopsy specimens is greatest 2 years after radiation therapy
      completion. Gleason grading is not reliable in the setting of hormonal ablation
      therapy. For patients with extracapsular extension, the survival curves separate
      depending on whether positive or negative surgical margins are obtained. Prostate
      specific antigen doubling time is increasingly used as an indicator of disease
      recurrence after local therapy and prostate cancer-specific survival.

PMID- 17021641
TI  - Hormonal therapy for prostate cancer.
AB  - Updates on hormonal therapy in the treatment of prostate cancer are presented.
      The most common therapy is to reduce testosterone to castrate levels. A dosage of
      1 mg diethylstilbestrol daily prolonged survival in patients with advanced
      prostate cancer. The leuteinizing hormone-releasing hormone agonists have
      essentially replaced surgical orchiectomy in the vast majority of clinical
      settings; however, a major problem with the leuteinizing hormone- releasing
      hormone agonists has been the surge and flare of testosterone levels. If hormonal
      therapy is initiated early, the risk of major complications is significantly
      decreased. Combined androgen blockade is better than monotherapy, although there
      is only a small clinical benefit. When androgen deprivation is used for a short
      time and the normal androgen milieu is re-established, the side effects and
      toxicity of androgen deprivation are decreased. The major complications of
      androgen deprivation include hot flushes, reduction of bone mineral density,
      osteoporosis, and anemia. Intermittent androgen blockade might have the same
      benefits of total androgen suppression with fewer side effects, increased
      duration of androgen dependence, and less cost. The 10 steps to take when
      advising patients about initiation of androgen deprivation therapy are reviewed.

PMID- 17021642
TI  - The treatment of hormone-refractory prostate cancer: docetaxel and beyond.
AB  - Two randomized clinical trials demonstrated a survival benefit of 20% to 24% with
      docetaxel-based therapy when compared with survival with mitoxantrone and
      prednisone after failure of androgen ablation therapy. These studies supported
      the approval of docetaxel-based therapy for the treatment of metastatic hormone
      refractory prostate cancer by the US Food and Drug Administration in May 2005.
      Clinical trials in hormone-refractory prostate cancer are now focused on building
      on the survival improvement seen with docetaxel-based therapy. This article
      presents a summary of some of the more promising treatments and regimens for
      advanced prostate cancer.

PMID- 17021644
TI  - Prevention, complementary therapies, and new scientific developments in the field
      of prostate cancer.
AB  - Prostate cancer prevention and therapies were reviewed in a recent update.
      Finasteride, a 5alpha reductase inhibitor, shows promise as a preventative;
      however, it may increase the incidence of high-grade cancer. There are ongoing
      studies regarding the positive effects of antioxidant therapy (vitamin E,
      selenium, and lycopene) on the prevention of prostate cancer; initial results are
      promising. Lipid-lowering drugs are associated with a statistically significant
      reduction in prostate cancer incidence, a 46% reduction in risk of high-grade or
      high-stage prostate cancer, and a 66% reduction in mortality from prostate
      cancer. Overexpression of transcription factors is caused by translocation of the
      promoter of the TMPRSS2 gene, which may be a primary event in prostate cancer.
      Immunomic profiling with use of autoantibodies directed against prostate-specific
      antigens may be used to identify cases of prostate cancer.

PMID- 17021643
TI  - Treatment- and disease-related complications of prostate cancer.
AB  - One of the highlights of the 16th International Prostate Cancer Update was a
      session on treatment- and disease-related complications of prostate disease. It
      began with presentation of a challenging case of rising prostate-specific antigen
      levels after radical prostatectomy, followed by an overview of the use of
      zoledronic acid in prostate cancer, a review of side effects of complementary
      medicines, an overview of complications of cryotherapy, an assessment of
      complications of brachytherapy and external beam radiation therapy, and a
      comparison of laparoscopy versus open prostatectomy.

PMID- 17021645
TI  - Practical management strategies for diaper dermatitis.
AB  - Common diaper dermatitis is an irritant contact diaper dermatitis (IDD) created
      by the combined influence of moisture, warmth, urine, feces, friction, and
      secondary infection. It is difficult to completely eradicate these predisposing
      factors in a diapered child. Thus, IDD presents an ongoing therapeutic challenge
      for parents, family physicians, pediatricians, and dermatologists. This article
      will focus on practical management strategies for IDD.

PMID- 17021646
TI  - Plasma skin regeneration technology.
AB  - Plasma skin regeneration (PSR) technology uses energy delivered from plasma
      rather than light or radiofrequency. Plasma is the fourth state of matter in
      which electrons are stripped from atoms to form an ionized gas. The plasma is
      emitted in a millisecond pulse to deliver energy to target tissue upon contact
      without reliance on skin chromophores. The technology can be used at varying
      energies for different depths of effect, from superficial epidermal sloughing to
      deeper dermal heating. With the Portrait PSR device (Rhytec, Inc.) there are
      three treatment guidelines termed PSR1, PSR2, and PSR3. The PSR1 protocol uses a
      series of low-energy treatments (1.0,1.2 Joules) spaced 3 weeks apart. The PSR2
      protocol uses one high-energy pass (3.0, 4.0 Joules) performed in a single
      treatment, and the PSR3 protocol uses two high-energy passes (3.0 4.0 Joules)
      performed in a single treatment. All protocols improve fine lines, textural
      irregularities, and dyspigmentation; however, skin tightening is probably more
      pronounced with the high-energy treatments.

PMID- 17021648
TI  - Aorto-enteric fistula: CT findings.
AB  - The objective of this pictorial essay is to present the different CT findings
      encountered in patients with aorto-enteric fistulas (AEFs). An AEF is a rare and
      sometimes disastrous occurrence, responsible for intermittent or massive
      gastrointestinal hemorrhage and hematemesis. CT provides fast and effective
      evaluation in hemodynamically stable patients suspected of having an AEF.

PMID- 17021647
TI  - Molecular imaging in radiology: the latest fad or the new frontier?

PMID- 17021651
TI  - Diagnosis and treatment of an intramedullary cavernoma in a young male with an
      implanted cardiac pacemaker.

PMID- 17021652
TI  - Synthesis, conformation and biological activity of centrally modified
      pseudopeptidic analogues of For-Met-Leu-Phe-OMe.
AB  - For-Met-betaAlapsi[CSNH]-Phe-OMe (3), For-Met-betaAlapsi[CH2NH]-Phe-OMe (5), For
      Met-NH-pC6H4-SO(2-Phe-OMe 8a), For-Met-NH-mCH4-SO2-Phe-OMe (8b) and the
      corresponding N-Boc precursors (2, 4, 7a, b) have been synthesized and their
      activity towards human neutrophils has been evaluated in comparison with that
      shown by the reference tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe). Chemotaxis,
      lysozyme release and superoxide anion production have been measured. (1)H NMR
      titration experiments and IR spectra have been discussed in order to ascertain
      the preferred solution conformation adopted by the tripeptide 3 with particular
      reference to the presence of a folded conformation centred at the centrally
      positioned thionated beta-residue.

PMID- 17021653
TI  - Nefopam is more potent than carbamazepine for neuroprotection against veratridine
      in vitro and has anticonvulsant properties against both electrical and chemical
      stimulation.
AB  - Nefopam (NEF) is a known analgesic that has recently been shown to be effective
      in controlling both neuropathic pain and convulsions in rodents. In this study we
      compared nefopam to carbamazepine (CBZ), a reference antiepileptic drug (AED),
      for their ability to protect cerebellar neuronal cultures from neurodegeneration
      induced by veratridine (VTD). Furthermore, we tested nefopam for protection
      against both, maximal electroshock-induced seizures (MES), and isoniazid-induced
      seizures in mice. Both NEF and CBZ were effective in preventing both signs of
      excitotoxicity and neurodegeneration following exposure of cultures to 5 microM
      veratridine for 30 min and 24 h, respectively. Concentrations providing full
      neuroprotection were 500 microM CBZ and 50 microM NEF, while the concentration
      providing 50% neuroprotection was 200 microM for CBZ and 20 microM for NEF.
      Neither NEF nor CBZ reduced excitotoxicity following direct exposure of cultures
      to glutamate, but CBZ failed to reduce increases in intracellular calcium
      following stimulation of L-type voltage sensitive calcium channels. In vivo, NEF
      (20 mg/kg i.p.) significantly reduced MES and fully prevented MES-induced
      terminal clonus (TC). In comparison, NEF was significantly more effective than
      CBZ in preventing MES, although both drugs were equally effective against MES
      induced TC. Furthermore, nefopam provided protection against isoniazid-induced
      seizures at doses similar to those protecting against MES.

PMID- 17021654
TI  - The apoptotic effect of intercalating agents on HPV-negative cervical cancer C
      33A cells.
AB  - Cervical cancer is one of the leading causes of female cancer death worldwide
      with about 500,000 deaths per year. Both mitomycin C and cisplatin are alkylating
      agents, which bind and intercalate DNA, and thus used as anti-cancer drugs. In
      these studies, we focused on investigating the apoptotic effects of intercalating
      agents on HPV-negative cervical cancer C-33A cells. Accordingly, C-33A cells were
      treated with carboplatin, mitomycin C or cisplatin. Cell cycle analysis revealed
      that treatment with mitomycin C and cisplatin but not with carboplatin resulted
      in apoptosis. Both mitomycin C and cisplatin induced apoptosis in C-33A cells via
      caspase-8 and -3 processing in a Fas/FasL-dependent manner and also suppressed IL
      18 expression, while they down-regulated IkappaB expression and up-regulated p65
      expression. These results suggest that both mitomycin C and cisplatin induce
      apoptosis, not only via the caspase-8 and -3 dependent Fas/FasL pathway, but also
      via the regulation of NF-kappaB activity and IL-18 expression in HPV-negative
      cervical cancer C-33A cells.

PMID- 17021655
TI  - Detecting oxidative post-translational modifications in proteins.
AB  - Oxidative stress induces various post-translational modifications (PTM); some are
      reversible in vivo via enzymatic catalysis. The present paper reviews specific
      procedures for the detection of oxidative PTM in proteins, most of them including
      electrophoresis. Main topics are carbonylated and glutathionylated proteins as
      well as modification of selected amino acids (Cys, Tyr, Met, Trp, Lys).

PMID- 17021656
TI  - Isolation and characterization of mammalian D-aspartyl endopeptidase.
AB  - The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging
      has been implicated in the pathogenesis of Alzheimer's disease (AD), cataracts
      and arteriosclerosis. Here, we identified a specific lactacystin-sensitive
      endopeptidase that cleaves the D-Asp-containing protein and named it D-aspartyl
      endopeptidase (DAEP). DAEP has a multi-complex structure (MW: 600 kDa) and is
      localized in the inner mitochondrial membrane. However, DAEP activity was not
      detected in E. coli, S. cerevisiae, and C. elegans. A specific inhibitor for
      DAEP, i-DAEP: (benzoyl-L-Arg-L-His-[D-Asp]-CH(2)Cl; MW: 563.01), was newly
      synthesized and inhibited DAEP activity (IC(50), 3 microM), a factor of ten
      greater than lactacystin on DAEP. On the other hand, i-DAEP did not inhibit
      either the 20S or 26S proteasome. And we identified succinate dehydrogenase and
      glutamate dehydrogenase 1 as components of DAEP by affinity label using
      biotinylated i-DAEP. In the long life span of mammals, DAEP may serve as a
      scavenger against accumulation of racemized proteins in aging. Insights into DAEP
      will provide the foundation for developing treatments of diseases, such as AD, in
      which accumulation of D-Asp-containing proteins are implicated.

PMID- 17021657
TI  - Novel chemolithotrophic, thermophilic, anaerobic bacteria Thermolithobacter
      ferrireducens gen. nov., sp. nov. and Thermolithobacter carboxydivorans sp. nov.
AB  - Three thermophilic strains of chemolithoautotrophic Fe(III)-reducers were
      isolated from mixed sediment and water samples (JW/KA-1 and JW/KA-2(T): Calcite
      Spring, Yellowstone N.P., WY, USA; JW/JH-Fiji-2: Savusavu, Vanu Levu, Fiji). All
      were Gram stain positive rods (approximately 0.5 x 1.8 microm). Cells occurred
      singly or in V-shaped pairs, and they formed long chains in complex media. All
      utilized H(2) to reduce amorphous iron (III) oxide/hydroxide to magnetite at
      temperatures from 50 to 75 degrees C (opt. approximately 73 degrees C). Growth
      occurred within the pH(60C) range of 6.5-8.5 (opt. pH(60C) 7.1-7.3). Magnetite
      production by resting cells occurred at pH(60C) 5.5-10.3 (opt. 7.3). The iron
      (III) reduction rate was 1.3 mumol Fe(II) produced x h(-1) x ml(-1) in a culture
      with 3 x 10(7) cells, one of the highest rates reported. In the presence or
      absence of H(2), JW/KA-2(T) did not utilize CO. The G + C content of the genomic
      DNA of the type strain is 52.7 +/- 0.3 mol%. Strains JW/KA-1 and JW/KA-2(T) each
      contain two different 16S rRNA gene sequences. The 16S rRNA gene sequences from
      JW/KA-1, JW/KA-2(T), or JW/JH-Fiji-2 possessed >99% similarity to each other but
      also 99% similarity to the 16S rRNA gene sequence from the anaerobic,
      thermophilic, hydrogenogenic CO-oxidizing bacterium 'Carboxydothermus restrictus'
      R1. DNA-DNA hybridization between strain JW/KA-2(T) and strain R1(T) yielded 35%
      similarity. Physiological characteristics and the 16S rRNA gene sequence analysis
      indicated that the strains represent two novel species and are placed into the
      novel genus Thermolithobacter within the phylum 'Firmicutes'. In addition, the
      levels of 16S rRNA gene sequence similarity between the lineage containing the
      Thermolithobacter and well-established members of the three existing classes of
      the 'Firmicutes' is less than 85%. Therefore, Thermolithobacter is proposed to
      constitute the first genus within a novel class of the 'Firmicutes',
      Thermolithobacteria. The Fe(III)-reducing Thermolithobacter ferrireducens gen.
      nov., sp. nov. is designated as the type species with strain JW/KA-2(T) (ATCC
      700985(T), DSM 13639(T)) as its type strain. Strain R1(T) is the type strain for
      the hydrogenogenic, CO-oxidizing Thermolithobacter carboxydivorans sp. nov. (DSM
      7242(T), VKM 2359(T)).

PMID- 17021658
TI  - The phosphofructokinase-B (MJ0406) from Methanocaldococcus jannaschii represents
      a nucleoside kinase with a broad substrate specificity.
AB  - Recently, unusual non-regulated ATP-dependent 6-phosphofructokinases (PFK) that
      belong to the PFK-B family have been described for the hyperthermophilic archaea
      Desulfurococcus amylolyticus and Aeropyrum pernix. Putative homologues were found
      in genomes of several archaea including the hyperthermophilic archaeon
      Methanocaldococcus jannaschii. In this organism, open reading frame MJ0406 had
      been annotated as a PFK-B sugar kinase. The gene encoding MJ0406 was cloned and
      functionally expressed in Escherichia coli. The purified recombinant enzyme is a
      homodimer with an apparent molecular mass of 68 kDa composed of 34 kDa subunits.
      With a temperature optimum of 85 degrees C and a melting temperature of 90
      degrees C, the M. jannaschii nucleotide kinase represents one of the most
      thermoactive and thermostable members of the PFK-B family described so far. The
      recombinant enzyme was characterized as a functional nucleoside kinase rather
      than a 6-PFK. Inosine, guanosine, and cytidine were the most effective phosphoryl
      acceptors. Besides, adenosine, thymidine, uridin and xanthosine were less
      efficient. Extremely low activity was found with fructose-6-phosphate. Further,
      the substrate specificity of closely related PFK-Bs from D. amylolyticus and A.
      pernix were reanalysed.

PMID- 17021660
TI  - Protein biosensors based on the principle of fluorescence resonance energy
      transfer for monitoring cellular dynamics.
AB  - Genetically-coded, fluorescence resonance energy transfer (FRET) biosensors are
      widely used to study molecular events from single cells to whole organisms. They
      are unique among biosensors because of their spontaneous fluorescence and
      targeting specificity to both organelles and tissues. In this review, we discuss
      the theoretical basis of FRET with a focus on key parameters responsible for
      designing FRET biosensors that have the highest sensitivity. Next, we discuss
      recent applications that are grouped into four common biosensor design patterns-
      intermolecular FRET, intramolecular FRET, FRET from substrate cleavage and FRET
      using multiple colour fluorescent proteins. Lastly, we discuss recent progress in
      creating fluorescent proteins suitable for FRET purposes. Together these advances
      in the development of FRET biosensors are beginning to unravel the interconnected
      and intricate signalling processes as they are occurring in living cells and
      organisms.

PMID- 17021659
TI  - Cloning and characterization of dihydrofolate reductase from a facultative
      alkaliphilic and halotolerant bacillus strain.
AB  - Elucidation of the molecular basis of the stability of enzymes from extremophilic
      organisms is of fundamental importance for various industrial applications. Due
      to the wealth of structural data from various species, dihydrofolate reductase
      (DHFR, EC 1.5.1.3) provides an excellent model for systematic investigations. In
      this report, DHFR from alkaliphilic Bacillus halodurans C-125 was cloned and
      expressed in E. coli. Functional analyses revealed that BhDHFR exhibits the most
      alkali-stable phenotype of DHFRs characterized so far. Optimal enzyme activity
      was observed in a slightly basic pH region ranging from 7.25 to 8.75. Alkali
      stability is associated with a remarkable resistance to elevated temperatures
      (half-life of 60 min at 52.5 degrees C) and to high concentrations of urea (up to
      3 M). Although the secondary structure shows distinct similarities to those of
      mesophilic DHFR molecules, BhDHFR exhibits molecular features contributing to its
      alkaliphilic properties. Interestingly, the unique phenotype is diminished by C
      terminal addition of a His-tag sequence. Therefore, His-tag-derivatized BhDHFR
      offers the opportunity to obtain deeper insights into the specific mechanisms of
      alkaliphilic adaption by comparison of the three dimensional structure of both
      BhDHFR molecules.

PMID- 17021661
TI  - Adsorption of human IgG on to poly(N-isopropylacrylamide)-based polymer
      particles.
AB  - Thermosensitive poly(N-isopropylacrylamide)-based polymer particles were
      synthesised, and screened for the adsorption of human immunoglobulin G (hIgG). At
      pH 9 the adsorption on microgel particles was strongly affected by temperature,
      approximately 40 mg hIgG/g support (90% of initial hIgG) being adsorbed at 40
      degrees C but only 10% of initial hIgG at 25 degrees C. At pH 5 the maximum
      adsorbed amount (20 mg hIgG/g support) was similar for both temperatures. The
      adsorption of hIgG on to charged poly(methyl methacrylate)/poly(N
      isopropylacrylamide) core-shell latexes was negligible (5-10 mg hIgG/g support)
      at the same temperature and pH conditions. The lower adsorption of hIgG onto the
      core-shell particles is explained by steric interactions due to the small size of
      the shell.

PMID- 17021662
TI  - Phase partition of gaseous hexane and surface hydrophobicity of Fusarium solani
      when grown in liquid and solid media with hexanol and hexane.
AB  - The filamentous fungus, Fusarium solani, was grown in liquid and solid culture
      with glucose, glycerol, 1-hexanol and n-hexane. The partition coefficient with
      gaseous hexane (HPC) in the biomass was lower when grown in liquid medium with 1
      hexanol (0.4) than with glycerol (0.8) or glucose (1) The HPC for surface growth
      were 0.2 for 1-hexanol, 0.5 for glycerol, 0.6 for glucose, and 0.2 for F. solani
      biomass obtained from a biofilter fed with gaseous n-hexane. These values show a
      200-fold increase in n-hexane solubility when compared to water (HPC = 42). Lower
      HPC values can be partially explained by increased lipid accumulation with 1
      hexanol, 10.5% (w/w) than with glycerol (8.5% w/w) or glucose (7.1% w/w). The
      diameter of the hyphae diminished from 3 microm to 2 microm when F. solani was
      grown on solid media with gaseous n-hexane thereby doubling the surface area for
      gaseous substrate exchange. The surface hydrophobicity of the mycelia increased
      consistently with more hydrophobic substrates and the contact angle of a drop of
      water on the mycelial mat was 113 degrees when grown on n-hexane as compared to
      75 degrees with glucose. The fungus thus adapts to hydrophobic conditions and
      these changes may explain the higher uptake of gaseous hydrophobic substances by
      fungi in biofilters.

PMID- 17021663
TI  - Cutaneous leukocytoclastic vasculitis associated with mycobacterial and
      salmonella infection.
AB  - We describe the clinical and laboratory features, treatment, and outcome of five
      children with cutaneous leukocytoclastic vasculitis associated with salmonella
      infection seen at our hospital.

PMID- 17021664
TI  - The effect of gallium arsenide aluminum laser therapy in the management of
      cervical myofascial pain syndrome: a double blind, placebo-controlled study.
AB  - The efficacy of low-level laser therapy (LLLT) in myofascial pain syndrome (MPS)
      seems controversial. A prospective, double-blind, randomized controlled trial was
      conducted in patients with chronic MPS in the neck to evaluate the effects of low
      level 830-nm gallium arsenide aluminum (Ga-As-Al) laser therapy. The study group
      consisted of 64 MPS patients. The patients were randomly assigned into two
      groups. In group 1 (n = 32), Ga-As-Al laser treatment was applied over three
      trigger points bilaterally for 2 min over each point once a day for 15 days
      during a period of 3 weeks. In group 2 (n = 32), the same treatment protocol was
      given, but the laser instrument was switched off during applications. All
      patients in both groups performed daily isometric exercise and stretching
      exercises for cervical region. Parameters were measured at baseline and after 4
      weeks. All patients were evaluated with respect to pain (at rest, movement, and
      night) and assessed by visual analog scale, measurement of active range of motion
      using an inclinometer and a goniometer, and the neck disability index. In both
      groups, statistically significant improvements were detected in all outcome
      measures compared with baseline (p < 0.05). However, no significant differences
      were obtained between the two groups (p > 0.05). In conclusion, although the
      laser therapy has no superiority over placebo groups in this study, we cannot
      exclude the possibility of effectivity with another treatment regimen including
      different laser wavelengths and dosages (different intensity and density and/or
      treatment interval).

PMID- 17021665
TI  - Response to one infusion predicts subsequent improvement as well as the rate of
      relapse of ankylosing spondylitis infused with three pulses of infliximab.
AB  - The objective of this study was to evaluate if there are early clinical
      parameters in AS patients treated with three standard infusions of infliximab,
      which would predict whether a patient will derive a significant improvement at
      the tenth week, or whether there will be a lengthy clinical response after
      discontinuing the infusions. Sixty three AS patients were given three infusions
      of 5 mg/kg of infliximab at weeks 0, 2, and 6 and evaluated serially before each
      infusion and also at week 10. Afterwards, patients were followed up by telephone
      interview until their disease activities were >60% of the baseline values. At
      that point, disease was considered to have relapsed. Clinical parameters at
      baseline as well as at week 2 were used for analysis to identify factors that
      might predict an improvement at week 10, or predict a delayed relapse. A
      predictor is regarded as being useful if the area under the curve (AUC) when
      analyzed by receiver operator calculations (ROC) exceeds 0.75. No parameters at
      baseline have sufficient predictive values. However, ASAS20 (Assessment in
      Ankylosing Spondylitis International Working Group criteria) at week 2 predicts
      improvement at week 10, and also duration of clinical response after
      discontinuing the infliximab at week 6. The response to one pulse of infliximab
      is the best predictor of subsequent response as well as rate of relapse after
      discontinuing the infliximab.

PMID- 17021666
TI  - Standardization is essential for a more rigorous comparison of rates: comment on
      the reply by Gilgil, Kacar, and Tuncer.

PMID- 17021667
TI  - Influence of corticosteroid treatment on MRI findings in giant cell arteritis.
AB  - Giant cell arteritis (GCA) remains a diagnostic challenge. With the use of a high
      resolution MRI protocol, visualization of the superficial cranial arteries is
      feasible and mural inflammation can be assessed noninvasively. Until today, it is
      not known how soon inflammatory signals in diagnostic MR imaging vanish after
      initiation of treatment. Here, we report sequential MR imaging findings during
      the initial weeks of corticosteroid treatment in a 79-year-old female patient
      with histologically proven GCA. Mural inflammatory changes decreased within the
      first 2 weeks and have almost entirely vanished after 2 1/2 months of continued
      treatment. Moreover, MR angiography revealed sequential stenoses of the
      subclavian artery, which improved in variable extent with some residuals despite
      high dose steroid medication. This report underlines the value of high-resolution
      MRI in diagnosis and follow-up of GCA and illustrates the potential of MRI to
      detect and monitor intra- and extra-cranial involvement patterns of GCA in high
      detail.

PMID- 17021668
TI  - Clinical features, prognostic and risk factors of central nervous system
      infections in patients with systemic lupus erythematosus.
AB  - The purpose of this study is to describe the etiology, characteristics and
      outcomes of central nervous system (CNS) infections in patients with systemic
      lupus erythematosus (SLE), while also identifying prognostic and risk factors.
      Thirty-eight SLE patients with CNS infections were identified from review of all
      charts of patients with SLE hospitalized from January 1995 to June 2005. These
      patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non
      TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS
      infections, TB was identified in 19 patients, Listeria monocytogenes in 3
      patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient,
      Gram's stain positive bacteria in 1 patient, Cryptococcus neoformans in 12
      patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome
      in patients with fungal infection was lower than in patients with TB (P=0.028)
      and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS
      infections had a more insidious or atypical clinical presentation. Compared to
      SLE patients without CNS infections, those with CNS infections were more likely
      to have low serum albumin levels (P=0.048) and have been receiving higher doses
      of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of
      prednisolone within the previous year (P=0.039). In conclusion, low levels of
      serum albumin and higher doses of received prednisolone are important risk
      factors for the development of CNS infections in SLE patients.

PMID- 17021669
TI  - Influence of intraarticular corticosteroid administration on serum cytokines in
      rheumatoid arthritis.
AB  - Though the efficacy of intraarticular (IA) corticosteroid administration in the
      therapeutic management of rheumatoid arthritis (RA) has been well documented, its
      immunomodulatory effects have not been defined. Categorization of these effects
      is important to develop safe derivative therapeutic strategies with a more
      targeted mechanism of action as they relate to the pathophysiology of RA. We
      describe here a broad spectrum immune response to inflammation as evidenced by
      rapid transient systemic inhibitory effects on key inflammatory regulators
      induced by the effects of IA administration of triamcinolone acetonide in a case
      of active RA who failed to respond to methotrexate.

PMID- 17021670
TI  - Increased seropositivity of Helicobacter pylori cytotoxin-associated gene-A in
      Behcet's disease.
AB  - Behcet's disease is a systemic vasculitic syndrome with unknown etiology. The aim
      of the present study was to compare the Helicobacter pylori seropositivity and
      cytotoxin associated gene-A status in patients with Behcet's disease. Ninety-one
      patients with Behcet's disease and 83 age- and sex-matched persons with or
      without any gastrointestinal complaints were included in the study. Demographic
      characteristics and H. pylori IgG, IgM, and cytotoxin-associated gene-A IgG
      status of the Behcet's disease and the control groups were analyzed. The
      influence of eradication therapy on clinical findings was also determined. The
      prevalence of H. pylori IgG seropositivity was slightly but not significantly
      higher in patients with Behcet's disease compared to the controls [72 (79.1%) vs
      56 (67.5%), (p = 0.082)]. The prevalence of cytotoxin-associated gene A
      positivity was significantly higher in Behcet's disease compared to the controls
      [59 (64.8.%) vs 32 (38.5%), respectively, (p = 0.002)]. Eradication of H. pylori
      has significantly decreased clinical manifestations such as oral and genital
      ulceration, arthritis/arthralgia, and cutaneous findings of Bahcet's disease. Our
      study indicates that H. pylori may be involved in the pathogenesis of Behcet's
      disease or disease activity might be enhanced due to induced inflammation or
      altered immunity.

PMID- 17021671
TI  - Association of acute anterior uveitis with disease activity, functional ability
      and physical mobility in patients with ankylosing spondylitis: a cross-sectional
      study of Chinese patients in Taiwan.
AB  - Acute anterior uveitis (AAU) is the most frequently extra-articular manifestation
      of ankylosing spondylitis (AS). To investigate whether AAU has an association
      with disease activity, functional ability and physical mobility in AS patients,
      146 Chinese AS patients in Taiwan were enrolled in a cross-sectional study. These
      patients fulfilled the 1984 modified New York criteria and visited the Outpatient
      Department of the Veterans General Hospital-Taipei from April 2004 to July 2005.
      Patients completed questionnaires assessing disease activity [Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI)], functional ability [Bath Ankylosing
      Spondylitis Functional Index (BASFI)] and patient's global assessment [Bath
      Ankylosing Spondylitis Patient Global Score (BAS-G)]. Meanwhile, physical
      examinations were performed, including Schober test, finger-to-floor, lateral
      spinal flexion, occiput-to-wall and chest expansion. The history of AAU was
      accepted only if diagnosed by an ophthalmologist. The prevalence of AAU in this
      Chinese AS cohort was 15.8% (23/146). Patients with AAU had a significantly
      higher BASDAI than those without [absolute differences=0.96, 95% confidence
      intervals (CI): 0.35-1.88]. Additionally, patients with AAU had significantly
      increased BASFI than those without (absolute differences=1.46, 95% CI: 0.33
      2.59). Moreover, there was advanced limitation of physical motility in patients
      with AAU, including finger-to-floor, occiput-to-wall distances and Schober test,
      (95% CI: 3.89-16.95 and p=0.046, respectively). Disease duration mildly
      correlated with BASFI (r=0.24, p=0.003) but not with BASDAI (p=0.838). There was
      no difference of disease duration between patients with and without AAU
      (p=0.343). These results suggested that the presence of AAU in AS patients may be
      associated with higher disease activity, poor functional ability and advanced
      physical impairment.

PMID- 17021672
TI  - Pelvic arterial embolization in the setting of acute hemorrhage as a result of
      the anterior Prolift procedure.
AB  - Acute hemorrhage following pelvic reconstructive surgery is a complication
      requiring immediate evaluation and treatment. Therapeutic options include fluid
      resuscitation, tamponade techniques, exploratory surgical intervention, and, more
      recently, pelvic vessel embolization. New approaches to pelvic organ prolapse
      have been evolving rapidly with little reported on safety and efficacy. We
      present a 77-year-old female who had a life-threatening acute pelvic hemorrhage
      from an anterior Prolift procedure successfully treated with pelvic artery
      embolization.

PMID- 17021675
TI  - Laparoscopic cure of small ventral hernias with composite mesh.
AB  - BACKGROUND: The use of mesh is recommended to reduce the rate of recurrence after
      the curing of ventral hernias. METHODS: A multicentre prospective trial was
      conducted to assess the laparoscopic cure of small ventral hernias with a
      composite mesh. RESULTS: Around 222 patients entered the trial and received
      laparoscopic repair for ventral hernias of less than 5 cm. There was one
      conversion. The mean length of post-operative hospitalisation was 2.5 days. At 1
      year, the recurrence rate was 2%. Two meshes were removed due to infection, 3% of
      the patients were using analgesics and 86.1% of the patients described no pain on
      EVA scoring. CONCLUSION: The laparoscopic cure of small ventral hernias with
      composite mesh is efficient. Further technical progress is warranted to reduce
      the rate of seroma formation.

PMID- 17021673
TI  - Collagen metabolism and recurrent hiatal hernia: cause and effect?
AB  - Hiatus hernia (HH) is a condition characterized by herniation of the intra
      abdominal organs into the thorax. Of the several types that have been identified,
      the most common is type I (sliding) HH. Congenital predisposition and acquired
      factors, for example trauma and iatrogeny, have been identified as causative
      factors. There is a strong association between gastroesophageal reflux disease
      and HH-the prevalence of reflux in HH may reach 94%. Many methods have been used
      to treat reflux disease and HH, among which are laparoscopic techniques, which
      gained popularity as a safe method of treatment. Primary crural repair without
      mesh application was found to have a recurrence rate of up to 42%. This led to
      the introduction of mesh in HH repair, which was associated with a significant
      decrease in recurrence rate. Collagen and its relation to hernia have been
      investigated for several decades. Collagen has mechanical properties sufficient
      to enable it to support healed scars and other tissues. Nineteen distinct types
      of collagen have been recognized, the most common of which are types I and III.
      Type III collagen is the major constituent of early granulation tissue whereas
      type I predominates as healing proceeds. Collagen fibers are imbedded in
      extracellular matrix (ECM), which is in continuous process of synthesis and
      degradation under the action of matrix metalloproteinases. Many authors have
      studied the role of collagen in ventral hernia and have even defined hernia as a
      disease of the ECM. The relationship between collagen and HH, and its recurrence,
      is not fully understood and needs further investigation.

PMID- 17021677
TI  - Nicotine induces oxidative stress and activates nuclear transcription factor
      kappa B in rat mesencephalic cells.
AB  - Cigarette smoke is a complex mixture of more than 4700 chemical compounds
      including free radicals and oxidants. Toxicity exhibited by cigarette smoke may
      be due to combined action of these compounds inducing many cellular processes
      mediated through reactive oxygen species (ROS). Major player probably nicotine as
      it is present in tobacco, in higher concentrations. The compounds that induce
      intracellular oxidative stress recognized as the important agents involved in the
      damage of biological molecules. Experiments using animal and cell culture model
      systems suggested that moderately higher concentrations of some forms of ROS like
      NO and H(2)O(2) can act as signal transducing agents. Nuclear transcription
      factor kappaB (NF-kappaB) an inducible transcription factor detected in neurons
      found to be involved in many biological processes such as inflammation, innate
      immunity, development, apoptosis, and antiapoptosis. Our present study
      demonstrates that nicotine induces ROS levels in a dose dependent manner in rat
      mesencephalic cells. Electro mobility shift analysis showed that nicotine
      activates inducible NF-kappaB by binding to consensus sequence of DNA. Nicotine
      added to cell culture stimulates the degradation of IkappaB-alpha subunit in 2 h.
      Further activation of c-Jun terminal kinase indicates that nicotine induces
      oxidative stress leading to activation of stress dependent NF-kappaB pathway in
      mesencephalic cells.

PMID- 17021678
TI  - Genetics and heritability of coronary artery disease and myocardial infarction.
AB  - A positive family history is frequently reported by patients with coronary artery
      disease (CAD) or myocardial infarction. For risk stratification, it is crucial to
      distinguish between accidental reoccurrence of sporadic cases and cases with a
      true heritable component of the conditions. A familial predisposition is assumed
      when a myocardial infarction is diagnosed by a male first degree relative before
      the 55th year of life or a female first degree relative before the 65th year of
      life. The current manuscript reviews major studies from which a familial risk of
      CAD or myocardial infarction can be inferred. Moreover, a brief overview
      summarizes the current results of molecular genetic research on chromosomal loci
      and genes relevant for CAD and myocardial infarction.

PMID- 17021679
TI  - Opposite effects of vascular irradiation on inflammatory response and apoptosis
      induction in the vessel wall layers via the peroxynitrite-poly(ADP-ribose)
      polymerase pathway.
AB  - PURPOSE: We investigated in a surgical rat model of vascular injury the potential
      role of the peroxynitrite - poly(ADPribose) polymerase (PARP) pathway in
      inflammatory response and apoptosis induction after vascular gamma irradiation.
      METHODS: Male Sprague-Dawley rats underwent left carotid endarterectomy with
      removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or
      20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10).
      Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n =
      10) to distinguish between primary effects of vascular injury and secondary
      effects due to irradiation. RESULTS: After 21 days, neointima formation was
      significantly suppressed after irradiation (control: 0.07 mm(2) +/- 0.04 mm(2),
      15 Gy: 0.003 mm(2) +/- 0.004 mm(2), 20 Gy: 0.001 mm(2) +/- 0.0006 mm(2), P<
      0.0001). However, a significant inflammation of the vessel wall with focal wall
      necrosis was detected (control: 0.2 +/- 0.15, 15 Gy: 0.82 +/- 1.2, 20 Gy: 1.25 +/
      0.86, P= 0.003). Immunohistochemistry showed significant staining for
      nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing
      factor in the neointima of the control group. In the irradiated groups these
      stainings were significantly higher in the media and adventitia compared to the
      non-irradiated groups. CONCLUSION: Activation of the peroxynitrite-PARP pathway
      was demonstrated during neointima proliferation in a rat model of surgical
      vascular injury. Vascular irradiation suppressed neointima formation, but induced
      significant activation of the peroxynitrite - PARP pathway in the outer vessel
      wall layers concomitant to inflammation and focal wall necrosis. This may
      contribute to adverse effects of vascular irradiation such as fibrosis and
      constrictive remodeling.

PMID- 17021680
TI  - Pulmonary regurgitation is a powerful factor influencing QRS duration in patients
      after surgical repair of tetralogy of Fallot. A magnetic resonance imaging (MRI)
      study.
AB  - AIMS: QRS prolongation is a negative prognostic factor for the development of
      ventricular arrhythmia after repair of tetralogy of Fallot (TOF). In this MRI
      study, we performed a multivariate analysis to determine the influence of
      volumetric and functional parameters as well as time factors on QRS duration.
      METHODS AND RESULTS: Sixty-seven patients after surgical repair of TOF were
      studied using a 1.5T MRI. Measurement of the ventricles was performed with a
      multislice-multiphase sequence. Left and right ventricular volumes, ejection
      fractions (EF) and myocardial masses were determined. Pulmonary regurgitant
      fraction (PRF) was quantified by velocity encoded flow measurement in the main
      pulmonary artery. Maximum QRS duration was taken from a 12-channel ECG. Mean
      maximum QRS duration was 132 ms (+/- 29 ms). Mean PRF was 29.2% (+/- 13.4%). QRS
      duration correlated significantly with PRF (r = 0.49; p < 0.01; n = 54) and with
      right ventricular enddiastolic volume index (RVEDVI) (r = 0.29; p < 0.05; n =
      67). Multivariate analysis revealed that the combination of PRF, postoperative
      period, age at surgical repair, and left ventricular (LV) enddiastolic volume are
      correlated with QRS prolongation. CONCLUSION: In patients after repair of TOF,
      pulmonary regurgitation is related to QRS prolongation. Furthermore, even LV size
      plays a role in the enlargement of the QRS complex.

PMID- 17021681
TI  - A 12-year follow-up study of malpractice claims against radiologists in Italy.
AB  - PURPOSE: Malpractice claims filed against radiologists have become a relevant
      phenomenon in Italy and are a real risk in the radiologists' professional
      activity. MATERIALS AND METHODS: Insurance claims of Italian radiologists over
      the 1993-2004 period were anonymously assessed. A total of 990 insurance claims
      were classified according to cause: (1) missed diagnosis, (2) complications of
      the radiological procedure, (3) failure to order further radiological
      examinations, (4) radiation treatment, (5) slip-and-fall injuries, (6)
      miscellaneous causes. RESULTS: A total of 990 claims were filed during the
      period, with most claims being filed a considerable time after the event. As a
      consequence, the estimated incidence may be 44 per 1,000. In other words, 44% of
      Italian radiologists have received, or will receive, a summons regarding their
      professional activity of the past 10 years. Misdiagnosis made up the first and
      most important claim category. Missed abnormalities on breast radiographs
      accounted for the greatest percentage of cases. Missed bone abnormalities were
      the following most common diagnostic errors. Complications following
      interventional procedures accounted for 10% of all cases. A few cases resulted
      from the radiologist's failure to order further diagnostic examinations. Lastly,
      radiologists were frequently named as one of multiple defendants, together with
      medical (or surgical) doctors, in cases of patient death in roughly 6% of all
      cases. CONCLUSIONS: The risk of medical malpractice litigation for Italian
      radiologists is by now comparable to that for American radiologists. Strict
      adherence to radiological standards may be a means of reducing the risk of legal
      action and obviating litigation.

PMID- 17021682
TI  - Role of SPECT/CT in the preoperative assessment of hyperparathyroid patients.
AB  - PURPOSE: Our purpose was to assess the clinical value and additional benefit of
      fusion single-photon computed tomography (SPECT) and computed tomography (CT)
      images in locating the parathyroids in a selected group of patients affected by
      primary (PHP) and secondary hyperparathyroidism (SHP). MATERIALS AND METHODS:
      Sixteen patients (11 women and five men; age range 35-80 years) with severe
      hyperparathyroidism (HP) (ten PHP, six SHP) were studied by ultrasound (US), and,
      after i.v. injection of 370 MBq of 99mTc-sestamibi, by planar parathyroid
      scintigraphy, SPECT and SPECT/CT using a dual-detector scintillation camera GE
      Infinia Hawkeye. All patients underwent parathyroidectomy. RESULTS: US findings
      were inconclusive in 12/16 patients affected by multinodular goitre, and two
      probable eutopic parathyroid glands were identified. "Double phase" parathyroid
      scintigraphy identified 14 probable parathyroid glands, SPECT 23 (14 ectopic and
      nine eutopic) and SPECT/CT confirmed all 23 probable parathyroid lesions,
      offering more precise localisation and an evident improvement in diagnostic
      accuracy. Sixteen of these foci of increased uptake were hyperplastic parathyroid
      glands, six were adenomas, one was a parathyroid carcinoma and one was a thyroid
      follicular carcinoma. Surgical detection of the 23 sestamibi-positive lesions was
      correctly matched with 100% of SPECT/CT images and 61% of SPECT data alone.
      Hybrid imaging thus provided additional data in 39% of lesions, and in three
      patients with retrotracheal glands, it modified the surgical approach.
      CONCLUSIONS: We believe 99mTc-sestamibi SPECT/CT to be a more reliable
      presurgical method to study a patient subgroup affected by PHP or SHP in whom
      conventional US and other scintigraphic methods have failed for intrinsic reasons
      due to the concomitant presence of multinodular goitre or ectopic parathyroid
      gland. The additional practical benefit derived from this methodology was
      evident. In fact, anatomical information provided by CT enables precise
      localisation of the functional abnormalities highlighted by SPECT, and both are
      essential to a correct surgical approach.

PMID- 17021683
TI  - Incidentally discovered thyroid nodules: incidence, and greyscale and colour
      Doppler pattern in an adult population screened by real-time compound spatial
      sonography.
AB  - PURPOSE: Our aim was to assess the incidence and ultrasound features of thyroid
      nodules in an adult population screened by means of high-resolution
      ultrasonography (HRUS) and to evaluate the contribution of real-time spatial
      compound sonography (CS) in terms of image quality. MATERIALS AND METHODS: A
      total of 704 consecutive patients (400 women, 304 men) without thyroid disease
      underwent HRUS and CS examination of the thyroid gland. Number, size, location,
      echotexture and colour Doppler pattern of detected nodules were assessed. Two
      radiologists also assessed image quality of the two techniques. RESULTS: Seven
      hundred and eleven thyroid nodules (size range 0.18-4.1 cm; mean: 1.1 cm) were
      detected in 233 subjects (33.1%). Of these, 416 (58.5%) were found in 143 women
      whereas 295 (41.5%) were detected in 90 men. In both genders, the number of
      detected nodules increased with age, with the highest prevalence in the seventh
      decade (p<0.001). There were 461/711 (64.9%) thyroid nodules that were
      hypoechoic, and 449/711 (63.1%) had peripheral vascularity only (p<0.001). Fine
      needle aspiration (FNA) revealed no malignancies. CS was graded better than HRUS
      in 621/711 (87.3%) cases (p<0.001). CONCLUSIONS: The prevalence of benign, small,
      hypoechoic thyroid nodules with peripheral vascularity was high in our series,
      thus suggesting a conservative approach. CS provided better image quality
      compared with HRUS.

PMID- 17021684
TI  - Role of CT and MRI in the preoperative evaluation of auditory brainstem
      implantation in patients with congenital inner ear pathology.
AB  - PURPOSE: The purpose of this study was to evaluate the reliability of computed
      tomography (CT) and magnetic resonance imaging (MRI) in characterising cochlear
      nerve anomalies in auditory brainstem implant candidates with congenital hearing
      loss. MATERIALS AND METHODS: Seventeen patients affected by congenital
      sensorineural hearing loss were examined by CT and MRI. Inner ear malformations
      eligible for auditory brainstem implants were classified according to the
      Casselman classification. All patients subsequently received auditory brainstem
      implants. RESULTS: Suspected congenital anomalies were confirmed by CT and MRI in
      all 17 patients. There were 5/17 bilateral cochlear nerve aplasias and 12/17
      cochleovestibular anomalies. Of these, 5/12 patients had a common
      cochleovestibular cavity, 2/12 had bilateral cochlear aplasia and cochlear nerve
      agenesis, 1/12 had type I incomplete partition, 2/12 had type II incomplete
      partition and 2/12 had cochlear hypoplasia. CONCLUSIONS: Preoperative CT and MRI
      assessment of patients with sensorineural hearing loss is reliable. MRI provided
      additional information, identifying the possible absence of cochlear nerve and
      excluding other central nervous system (CNS) diseases.

PMID- 17021685
TI  - Conventional and diffusion-weighted MRI in progressive multifocal
      leukoencephalopathy: new elements for identification and follow-up.
AB  - PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a serious disorder
      that primarily affects individuals with a suppressed immune system. Few
      semiological elements help clearly distinguish PML from other diseases included
      in the differential diagnosis. Moreover, the clinical course of disease may be
      chronic or rapidly progressive, with different magnetic resonance imaging (MRI)
      patterns. The purpose of this study was to confirm the diagnostic value of
      conventional MRI sequences combined with diffusion-weighted imaging (DWI) in PML
      to identify those patients with worst prognosis. MATERIALS AND METHODS: We used
      both conventional MRI sequences and DWI to monitor four male patients aged
      between 40 and 50 years affected by PML. In two patients, the disease rapidly led
      to death whereas the other two patients presented a chronic course. RESULTS:
      Conventional MRI sequences enable detection of the extension of white matter
      lesions. DWI permits more accurate differentiation of the disease progression
      front, which exhibits low signal intensity in apparent diffusion coefficient
      (ADC) maps, from the central gliotic area of demyelinisation, characterised by
      high ADC values. Patients with rapidly evolving PML have a clear progression
      front on DWI, which seems to be very tenuous, if not absent, during the quiescent
      phases of the disease. CONCLUSIONS: The addition of DWI sequences to conventional
      MRI seems to be a valid method for accurately diagnosing PML and establishing the
      degree of disease progression.

PMID- 17021686
TI  - Management and endovascular treatment of symptomatic abdominal aortic aneurysms.
AB  - PURPOSE: Our aim is to verify the feasibility and effectiveness of endovascular
      treatment for symptomatic abdominal aortic aneurysms (AAAs) in urgencies and
      emergencies. MATERIALS AND METHODS: Over the past 51 months, we treated 38
      symptomatic AAAs with endovascular exclusion. In 23 haemodynamically stable
      patients, computed tomography (CT) angiography was performed before treatment,
      and AAA exclusion was carried out as an urgent procedure; 15 patients with
      haemorrhagic shock were examined by ultrasound (US) only in the emergency room
      whereas the procedure was carried out in emergency and planned using angiography.
      Time from presentation to treatment was 100 min on average (range: 50-150 min).
      We used 27 Excluder (Gore) and 11 Zenith (Cook) stentgrafts. The follow-up was
      performed with CT angiography after 1, 3, 6 and 12 months and yearly thereafter.
      RESULTS: The immediate technical success rate was 100%, and the perioperative
      mortality rate was 10.5%. At follow-up completed in 34 patients (range: 1-48
      months, mean: 19.2), we observed five endoleaks (14%) (four type 2: two
      thrombosed spontaneously and two were under observation at the time of writing;
      one type 3, treated with stent-graft extension) and one occlusion of a stentgraft
      leg (treated by femorofemoral bypass). CONCLUSIONS: Endovascular treatment of
      AAAs is a good therapeutic alternative even in urgency and emergency conditions
      where correct planning ensures technical results comparable with those obtained
      under elective conditions.

PMID- 17021687
TI  - Endovascular treatment of steno-occlusions of the infrarenal abdominal aorta.
AB  - PURPOSE: Our aim is to report our experience in the endovascular treatment of
      steno-occlusions of the infrarenal abdominal aorta. MATERIALS AND METHODS: We
      selected 19 patients (mean age 66.3 years, range 45-80): five with complete
      occlusion of the infrarenal aorta and both common iliac arteries (CIAs), four of
      which were associated with occlusion of the external iliac arteries (EIAs); three
      with complete occlusion and three with severe stenosis of the distal aorta with
      occlusion or stenosis of the CIAs and EIAs; and eight with focal severe stenosis
      of the infrarenal aorta. All patients were treated with direct stenting. RESULTS:
      Immediate technical success was 94.7% (18/19 cases). We observed two cases of
      distal embolism treated with thrombolysis, one case of mild renal failure and one
      case of transient angina abdominis. During the follow-up (mean 19.6 months; range
      6-48), 2/18 (11.1%) occlusions of an iliac stent occurred 1 and 3 months after
      the procedure (treated with local intra-arterial thrombolysis). The primary
      patency rate was 88.8% and the secondary patency rate was 100%. CONCLUSIONS:
      Direct stenting is a feasible and safe option for the treatment of infrarenal
      abdominal aortic steno-occlusions, especially in patients at high surgical risk,
      with good early and late clinical results.

PMID- 17021688
TI  - Morphological and functional modifications of the aneurysm-endograft complex
      following endoluminal treatment of abdominal aortic aneurysms.
AB  - PURPOSE: The aim of the study was to evaluate quantitatively the main
      morphological changes of the abdominal aortic aneurysm (AAA)-endograft (EG)
      complex following endovascular repair of infrarenal AAA and to evaluate the
      functional consequences of these changes in terms of rate of complications
      (endoleaks and thrombosis). We also assessed whether these morphological and
      functional changes were related to the size of the AAA and to the type of EG
      used. MATERIALS AND METHODS: Eighty-five patients (M/F=82/3; mean age at time of
      operation 70.5+/-3.5 years, range 49.9-89.6 years) who underwent endovascular
      treatment of infrarenal AAA between April 1997 and October 2004 with a follow-up
      of at least 1 month were considered. All images of 408 preoperative and
      postoperative computed tomography (CT) studies were reviewed. Statistical
      analysis was performed with log-rank test on the 85 patients grouped according to
      AAA diameter <50 mm or < or =50 mm, and on 75 patients grouped according to EG
      device used (AneuRx, Talent or Excluder). RESULTS: Morphological and dimensional
      changes involved the diameter (six cases) and length (14 cases) of AAA proximal
      neck, diameter (36 cases) and length (51 cases) of the aneurysm sac and shape of
      the stent-graft (47 cases). The prevalence of endoleaks was 37.6% whereas
      endoluminal thrombosis was observed in 27.1% of patients. AAA growth was
      significantly correlated (p=0.002) with the preprocedural diameter of the
      aneurysm sac whereas shrinkage was significantly correlated (p=0.0005) with the
      EG used. CONCLUSIONS: AAA growth was correlated with the diameter of the aneurysm
      sac while shrinkage was correlated with the EG used. During follow-up after
      endovascular repair, patients require careful evaluation of the morphological and
      dimensional features of the AAA and EG to promptly identify any changes that can
      anticipate major complications and even conversion to conventional surgery.

PMID- 17021689
TI  - Characterisation of carotid atherosclerotic plaque: comparison between magnetic
      resonance imaging and histology.
AB  - PURPOSE: The aim of this study was to identify and characterise by magnetic
      resonance imaging (MRI) carotid plaque constituents such as lipid-rich necrotic
      core, intraplaque haemorrhage and calcification in patients treated with carotid
      endarterectomy (CEA) using histological evaluation as the reference standard.
      MATERIALS AND METHODS: Nineteen patients (13 men and six women) scheduled for CEA
      between March and August 2004 were imaged on a 1.5-T scanner (Magnetom Symphony,
      Siemens, Erlangen, Germany). The protocol included four types of sequences [T1,
      T2, proton density (PD) and three-dimensional time of flight (3D-TOF)]. Images
      were reviewed for integrity of the fibrous cap, presence of lipid-rich necrotic
      core, intraplaque haemorrhage and calcification. Signal intensity was assessed
      relative to the adjacent sternocleidomastoid muscle. Four cross-sections for each
      lesion were compared with the corresponding histological specimens and
      independently reviewed by two radiologists and one pathologist. RESULTS: MRI
      detected lipid-rich necrotic core with a sensitivity and specificity of 91.6% and
      95.0%, respectively, whereas it defined intraplaque haemorrhage alone with a
      sensitivity and specificity of 91.6% and 100%, respectively. Calcification was
      recognised with a sensitivity and specificity of 80% and 93.7%, respectively.
      CONCLUSIONS: MRI is able to identify signs of carotid plaque instability with a
      high sensitivity and specificity. Therefore, it may be useful in evaluating and
      guiding the treatment of haemodynamically nonsignificant stenoses with a
      potential embolic risk and, in the future, to assess coronary plaque.

PMID- 17021690
TI  - Single-versus multidetector-row CT: comparison of sedation rates, conventional
      angiograms and motion artefacts in young children following liver
      transplantation.
AB  - PURPOSE: The aim of this study was to determine whether the use of multidetector
      computed tomography (MDCT) is associated with decreased sedation, frequency of
      motion artefacts and conventional angiograms compared with single-detector CT
      (SDCT). MATERIALS AND METHODS: CT examinations performed in young children
      between January 1993 and June 2005 were reviewed retrospectively. Prior to
      September 2000, SDCT was used; after that period, MDCT was used. The examinations
      obtained during these two periods were compared for the frequency of sedation,
      motion artefacts, and conventional angiograms. Statistical comparison between the
      two groups was determined by using the chi(2) test. RESULTS: A total of 126
      infants and children younger than 6 years of age underwent 134 CT examinations.
      Eighty-eight were obtained with a SDCT (65%) (group 1) and 46 with a MDCT (35%)
      (group 2). Sedation was required in 31/88 (35%) CT examinations in group 1 and in
      6/46 (13%) in group 2. Conventional angiography was performed in 20/88 (22%)
      cases in group 1 and in 6/46 (13%) in group 2. Motion artefacts were present in
      8/88 (9%) CT examinations in group 1 and in 4/46 (8%) in group 2. There was
      significant statistical difference with regard to sedation and angiography rates
      between the two groups (p<0.001) whereas there was no significant difference with
      regard to motion artefacts (p>1). CONCLUSIONS: MDCT can reduce the need for
      sedation and conventional angiography in children after liver transplantation.
      There is no effect on patient motion artefacts.

PMID- 17021691
TI  - Traumatic lesions of adrenal glands in paediatrics: about three cases.
AB  - Pediatric adrenal injuries, in blunt thoracoabdominal trauma, are rare and
      usually associated with traumatic liver and kidney lesions. This paper aims to
      present imaging findings and possible adrenal involvement in blunt abdominal
      traumas in childhood. We report three cases of thoracoabdominal trauma with
      adrenal involvement. Two patients were polytraumatised in car accidents. The
      third case was unusual because of the mild trauma. The adrenals lesions were
      right-sided in all cases. Post-traumatic adrenal contusion/haematoma may arise
      not only because of a direct trauma but also as a consequence of a sudden
      increase in the pressure in the inferior vena cava system-adrenal veins. This is
      why adrenal haemorrhage is not directly proportional to the trauma: compression
      of the inferior vena cava leads to increased pressure in the adrenal venous
      circulation, which supports the parenchymal lesion. The right adrenal gland is
      more frequently injured than the left gland: it can be easily compressed between
      the liver, spine and kidney, and its venous drainage flows directly into the
      inferior vena cava.

PMID- 17021692
TI  - Dynamic sonography of the forefoot in Morton's syndrome: correlation with
      magnetic resonance and surgery.
AB  - PURPOSE: The aim of this paper is to demonstrate the efficacy of the dynamic
      study of the forefoot during lateral compression of the metatarsal heads
      (Mulder's manoeuvre) in the visualisation of Morton's neuroma. The data were
      compared with clinical signs, conventional ultrasound (US), magnetic resonance
      (MR) and surgical findings. MATERIALS AND METHODS: Forty forefeet in 38 patients
      were investigated with conventional and dynamic US using a 10-MHz linear probe
      (Esaote Technos). MR was performed in 26 forefeet with a 0.2-T scanner (Esaote
      Artoscan). Twenty intermetatarsal spaces in 18 forefeet were explored surgically.
      RESULTS: Thirty-seven intermetatarsal masses were identified through dynamic US
      in the 40 forefeet investigated (two double localisations). This method was
      clearly more effective than conventional US, which could only locate 25. In those
      forefeet investigated with MR, it was possible to confirm dynamic US findings in
      16 out of 22. In one of the six cases unconfirmed by MR, a neuroma was removed
      following surgery. Twenty masses (19 neuromas and one synovial ganglion) were
      found in the 18 forefeet treated by surgery. CONCLUSIONS: Clinical evaluation,
      which is fundamental for accurate diagnosis, can make use of dynamic US in the
      first instance in order to confirm clinical signs and identify the correct site
      and number of masses. In our opinion, MR maintains a primary role in differential
      diagnosis with other diseases (mainly stress fractures, bursitis, ganglion cysts
      or tendon tumour sheaths).

PMID- 17021693
TI  - Pouch diverticula after vertical-banded gastroplasty.
AB  - PURPOSE: Diverticula of the proximal gastric pouch are rare after vertical-banded
      gastroplasty (VBG) for morbid obesity. We report the radiographic findings
      observed in a series of 12 patients with pouch diverticula. MATERIALS AND
      METHODS: Lesions were found along the posteromedial wall of the proximal gastric
      pouch and ranged in size from 10 to 25 mm. Only two patients were symptomatic at
      the time of diagnosis; in most cases, diverticula were discovered during studies
      performed as part of the standard follow-up protocol. Diverticula were followed
      up in 7/12 cases, and four showed slight enlargement over a period ranging from
      14 to 53 months. RESULTS: The presence of diverticula was not correlated with
      symptoms, postoperative weight loss, or clinical history, and no differences in
      long-term complications were demonstrated between VBG patients with diverticula
      and those without them. CONCLUSIONS: We do not believe these lesions to be
      clinically important; at present, our patients are no longer followed up for this
      problem and undergo diagnostic examinations only if and when they develop
      symptoms.

PMID- 17021694
TI  - Functional MRI in the evaluation of oesophageal motility: feasibility, MRI
      patterns of normality, and preliminary experience in subjects with motility
      disorders.
AB  - PURPOSE: The aim of this study was to introduce functional magnetic resonance
      imaging (fMRI) with T1-weighted turbo fast low-angle shot (FLASH) sequences in
      the evaluation of oesophageal motility and morphology, to formulate MRI patterns
      of normality in healthy subjects and to demonstrate the feasibility of the method
      by obtaining a preliminary experience in the study of subjects affected by
      oesophageal motility disorders. MATERIALS AND METHODS: Thirty healthy volunteers
      and seven patients with radiological and manometric diagnoses of oesophageal
      motility disorders underwent fMRI with dynamic T1- weighted turbo-FLASH (TFL)
      sequences during the administration of oral contrast material. RESULTS:
      Evaluation of oesophageal function and morphology proved possible in all
      subjects, as well as the formulation of normality patterns. In patients with
      motility disorders, fMRI correctly visualised the typical alterations in
      agreement with radiological and manometric findings. CONCLUSIONS: Functional MRI
      sequences acquired during the administration of oral contrast material can
      evaluate oesophageal transit, providing information on motility and morphology;
      furthermore, this modality can properly visualise the typical functional and
      morphological alterations of motility disorders.

PMID- 17021698
TI  - N-acetyl-cysteine protects liver from apoptotic death in an animal model of
      fulminant hepatic failure.
AB  - BACKGROUND: This work was undertaken to investigate whether treatment with N
      acetyl-cysteine (NAC) prevents oxidative stress and inhibits the apoptotic
      pathways in an animal model of fulminant hepatic failure. METHODS: Rabbits were
      experimentally infected with 2x10(4) hemagglutination units of a rabbit
      hemorrhagic disease virus isolate. RESULTS: The spontaneous mortality rate of
      infected animals was 67% at 36 h post infection (pi) and 90% at 48 h pi. This
      percentage decreased significantly in animals receiving an i.p. injection of NAC
      (150 mg/kg body way/daily), for 7 days prior to infection. From 36 h pi marked
      increases were detected in blood levels of transaminases, lactate dehydrogenase,
      bilirubin and the oxidised/reduced glutathione ratio. All these effects were
      significantly prevented by NAC treatment. The Bax to Bcl-2 relative expression,
      the expression of FasL, cytochrome c and PARP-1, and the activity of caspase 3
      were significantly increased at 36 and 48 h pi in infected animals. These changes
      were markedly reduced in animals treated with NAC, with the exception of FasL.
      CONCLUSION: Our results suggest a potential hepatoprotective role of NAC in
      fulminant hepatic failure, mediated partially through the modulation of the
      intrinsic pathway of apoptosis.

PMID- 17021699
TI  - Gradient-enhanced volume rendering: an image processing strategy to facilitate
      whole small bowel imaging with MRI.
AB  - MRI of the small bowel with positive contrast from orally administered contrast
      agent is a promising non-invasive imaging method. The aim of our study was to
      introduce small bowel MRI in a display format that clinicians are accustomed to
      and that maximizes the amount of information visualized on a single image. Twelve
      healthy volunteers, median age 32 years (range 18-49 years) participated in the
      study. A mixture of 20 ml Gd-DOTA (Dotarem), 0.8 g/kg body weight psyllium fibre
      (Metamucil) and 1.2 l water were sequentially administered over a period of 4 h.
      Imaging was performed on a 1.5 T unit (Philips Gyroscan, Intera). Fat-saturated,
      3D, gradient echo imaging was performed while the patient was in apnea (30 s).
      Bowel motion was reduced with 40 mg intravenously administered scopolamine
      (Buscopan). A 3D, gradient-enhanced, volume rendering technique was applied to
      the 3D data sets. Standard projections [left anterior oblique (LAO), right
      anterior oblique (RAO), supine and prone] resembling conventional enteroclysis
      were successfully generated within fewer than 10 min processing time.
      Reconstructions were reproducible and provided an entire overview of the small
      bowel. In addition thin-slab volume rendering allowed an overlap-free display of
      individual structures. Positive contrast from orally administered contrast agent,
      combined with a gradient enhanced volume rendering method, allows the
      reconstruction of the small bowel in a pattern resembling conventional double
      contrast enteroclysis. Segmental display without overlay is possible.

PMID- 17021700
TI  - Pancreatic adenocarcinoma.
AB  - Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head
      of the pancreas in 60-70% of cases. By the time of diagnosis, at least 80% of
      tumors are unresectable. Helical computed tomography (CT) is very effective in
      detecting and staging adenocarcinoma, with a sensitivity of up to 90% for
      detection and an accuracy of 80-90% for staging, but it has limitations in
      detecting small cancers. Moreover, it is not very accurate for determining
      nonresectability because small liver metastases, peritoneal carcinomatosis, and
      subtle signs of vascular infiltration may be missed. Multidetector-row CT (MDCT)
      has brought substantial improvements with its inherent ability to visualize
      vascular involvement in three dimensions. MDCT has been found to be at least
      equivalent to contrast-enhanced magnetic resonance imaging (MRI) for detecting
      adenocarcinoma. MRI can be used as a problem-solving tool in equivocal CT: MRI
      may help rule out pitfalls, such as inflammatory pseudotumor, focal lipomatosis,
      abscess, or cystic tumors. Mangafodipir-enhanced MRI reveals a very high tumor
      pancreas contrast, which helps in diagnosing small cancers. Endosonography is, if
      available, also a very accurate tool for detecting small cancers, with a
      sensitivity of up to 98%. It is the technique of choice for image-guided biopsy
      if a histologic diagnosis is required for further therapy.

PMID- 17021701
TI  - Computer assisted detection software for CT colonography: effect of sphericity
      filter on performance characteristics for patients with and without fecal
      tagging.
AB  - The aim of this study is to investigate the effect of changing sphericity filter
      values on performance of a computer assisted detection (CAD) system for CT
      colonography for data with and without fecal tagging. Colonography data from 138
      patients with 317 validated polyps were divided into those with (86) and without
      (52) fecal tagging. Polyp coordinates were established by three observers and
      datasets analysed subsequently by a proprietary CAD system used at four discrete
      sphericity filter settings. Prompts were compared with the known coordinates in
      order to determine sensitivity and specificity. Sensitivity was highest at low
      sphericity; of 164 polyps 6 mm or more, 144 (87.8%) were detected at sphericity
      0.3, and 132 (80.1%) at sphericity 0.9. Of 42 polyps measuring 10 mm or more, 40
      (95.2%) were detected at sphericity 0.3, and 36 (85.7%) at sphericity 0.9. There
      was no significant difference in sensitivity for tagged and un-tagged data but
      specificity was reduced in tagged data at low sphericity and significantly
      reduced in untagged data at high sphericity. CAD had a sensitivity of 95.2% for
      polyps measuring 1 cm or more and 87.8% for polyps 6 mm or more when used at a
      sphericity setting of 0.3. Higher sphericity settings increased specificity while
      reducing sensitivity. The bowel preparation used significantly impacts on
      specificity.

PMID- 17021702
TI  - Imaging features of musculoskeletal involvement in systemic sclerosis.
AB  - This article describes the radiographic, sonographic and magnetic resonance (MR)
      features of musculoskeletal involvement in patients with systemic sclerosis
      (SSc). Conventional radiography is the traditional method of detecting digital
      calcifications, but ultrasonography (US) is also able to detect such
      calcifications before they appear on radiographs. MR imaging can be used to
      diagnose overlapping conditions (i.e., SSc and myositis or SSc and rheumatoid
      arthritis), and less frequently, to reveal neurologic complications of SSc. In
      patients with vascular ulcers, MR angiography is able to depict decreased flow
      within collateral digital arteries.

PMID- 17021703
TI  - Thyroid dose from common head and neck CT examinations in children: is there an
      excess risk for thyroid cancer induction?
AB  - This study was conducted to estimate thyroid dose and the associated risk for
      thyroid cancer induction from common head and neck computed tomography (CT)
      examinations during childhood. The Monte Carlo N-particle transport code was
      employed to simulate the routine CT scanning of the brain, paranasal sinuses,
      inner ear and neck performed on sequential and/or spiral modes. The mean thyroid
      dose was calculated using mathematical phantoms representing a newborn infant and
      children of 1year, 5 years, 10 years and 15 years old. To verify Monte Carlo
      results, dose measurements were carried out on physical anthropomorphic phantoms
      using thermoluminescent dosemeters (TLDs). The scattered dose to thyroid from
      head CT examinations varied from 0.6 mGy to 8.7 mGy depending upon the scanned
      region, the pediatric patient's age and the acquisition mode used. Primary
      irradiation of the thyroid gland during CT of the neck resulted in an absorbed
      dose range of 15.2-52.0 mGy. The mean difference between Monte Carlo calculations
      and TLD measurements was 11.8%. Thyroid exposure to scattered radiation from head
      CT scanning is associated with a low but not negligible risk of cancer induction
      of 4-65 per million patients. Neck CT can result in an increased risk for
      development of thyroid malignancies up to 390 per million patients.

PMID- 17021704
TI  - Image-guided radiofrequency ablation of renal cell carcinoma.
AB  - The incidence of renal cell carcinoma is rising with the increased number of
      incidental detection of small tumours. During the past few years, percutaneous
      imaging-guided radiofrequency ablation has evolved as a minimally invasive
      treatment of small unresectable renal tumours offering reduced patient morbidity
      and overall health care costs. In radiofrequency ablation, thermal energy is
      deposited into a targeted tumour by means of a radiofrequency applicator. In
      recent studies, radiofrequency ablation was shown to be an effective and safe
      modality for local destruction of renal cell carcinoma. Radiofrequency applicator
      navigation can be performed via ultrasound, computed tomography or magnetic
      resonance guidance; however, ultrasound seems less favourable because of the
      absence of monitoring capabilities during ablation. On-line monitoring of
      treatment outcome can only be performed with magnetic resonance imaging giving
      the possibility of eventual applicator repositioning to ablate visible residual
      tumour tissue. Long-term follow-up is crucial to assess completeness of tumour
      ablation. New developments in ablation technology and radiological equipment will
      further increase the indication field for radiofrequency ablation of renal cell
      carcinoma. Altogether, radiofrequency ablation seems to be a promising new
      modality for the minimally invasive treatment of renal cell carcinoma, which was
      demonstrated to exhibit high short-term effectiveness.

PMID- 17021705
TI  - Management of infracentimetric thyroid nodules with respect to ultrasonographic
      features.
AB  - An assumed indolent course of thyroid microcarcinomas and concerns about the cost
      effectiveness of treatment raise management issues. As various studies have
      reported controversial results, management remains unclear. The purpose of this
      study was to examine the use of ultrasonography (US) in detecting malignancies in
      a series of 589 infracentimetric nodules. Results of fine-needle aspiration
      biopsies (FNAB) revealed 503 nodules with adequate cytology. Of these, 473 (94%)
      were benign, 13 (2.6%) were suspicious for malignancy, 13 (2.6%) were malignant,
      and 4 (0.8%) were follicular neoplasms. Hypoechogenicity and accompanying
      lymphadenopathy were the independently significant features in detecting
      malignancies. Certain combinations of US features increase the significance and
      predictive value for malignant cytology particularly in the presence of
      lymphadenopathy. When the postoperative histological results of ten patients with
      a final diagnosis of papillary carcinoma were evaluated for extent of disease,
      seven (70%) had one or more of the findings of multifocality, metastatic lymph
      nodes, or extracapsular involvement, thus proving their clinical significance.
      Our results indicate that thyroid microcarcinomas should be taken seriously if
      there are possible signs of malignancy on US. With respect to the high benign
      nature of the micronodules (94%), the number of interventional procedures should
      be lowered by making assessments based on a combination of US features including
      lymphadenopathy.

PMID- 17021706
TI  - MR imaging of therapy-induced changes of bone marrow.
AB  - MR imaging of bone marrow infiltration by hematologic malignancies provides non
      invasive assays of bone marrow cellularity and vascularity to supplement the
      information provided by bone marrow biopsies. This article will review the MR
      imaging findings of bone marrow infiltration by hematologic malignancies with
      special focus on treatment effects. MR imaging findings of the bone marrow after
      radiation therapy and chemotherapy will be described. In addition, changes in
      bone marrow microcirculation and metabolism after anti-angiogenesis treatment
      will be reviewed. Finally, new specific imaging techniques for the depiction of
      regulatory events that control blood vessel growth and cell proliferation will be
      discussed. Future developments are directed to yield comprehensive information
      about bone marrow structure, function and microenvironment.

PMID- 17021707
TI  - Management of an incidentally discovered pulmonary nodule.
AB  - The incidental finding of a pulmonary nodule on computed tomography (CT) is
      becoming an increasingly frequent event. The discovery of such a nodule should
      evoke the possibility of a small bronchogenic carcinoma, for which excision is
      indicated without delay. However, invasive diagnostic procedures should be
      avoided in the case of a benign lesion. The objectives of this review article
      are: (1) to analyze the CT criteria defining benign nodules, nodules of high
      suspicion of malignancy and indeterminate nodules, (2) to analyze the diagnostic
      performances and limitations of complementary investigations requested to
      characterize indeterminate lung nodules, (3) to review the criteria permitting to
      assess the probability of malignancy of indeterminate nodules and (4) to report
      on the new guidelines provided by the Fleischner Society for the management of
      small indeterminate pulmonary nodules, according to their prior probability of
      malignancy.

PMID- 17021708
TI  - Image-guided core-needle biopsy of peripheral lymph nodes allows the diagnosis of
      lymphomas.
AB  - It is commonly admitted that the diagnosis of lymphomas can be assessed by the
      image-guided needle biopsy (IGNB) of deep lymph nodes. However, when peripheral
      lymph nodes are present, surgical dissection remains the standard strategy. The
      aim of this study was to evaluate the diagnostic yield of IGNB of peripheral
      lymph nodes in patients with suspected lymphomas. The records of 180
      multisampling IGNBs of peripheral lymph nodes in 180 patients were reviewed. One
      hundred and twenty-three IGNBs were observed at first diagnosis and 57 at
      progression using large-cutting core-biopsy needles ranging between 18 G and 14 G
      in size. Immunohistochemistry studies were performed in all cases and at least
      one biopsy was systematically frozen. A diagnosis of lymphoma with sufficient
      information such that a therapeutic decision could be made was obtained in 146 of
      the 152 patients with lymphoproliferative disorders (96%). IGNB was equally
      effective in making the correct diagnosis of lymphoma at the time of original
      diagnosis than at relapse. The results did not depend on the biopsy site, lymph
      nodes size, or needle type. We recommend that IGNB may be performed as an initial
      procedure for the diagnosis of lymphomas either in the presence of peripheral or
      deep lymph nodes, as it avoids surgery.

PMID- 17021709
TI  - Multi-detector row CT urography on a 16-row CT scanner in the evaluation of
      urothelial tumors.
AB  - The purpose of this study was to assess the role of multi-detector row CT
      urography (MDCTU), on a 16-row CT scanner in the evaluation of patients with
      painless hematuria, with emphasis placed in the detection of urothelial tumors.
      We retrospectively reviewed the MDCT urographies of 75 patients, referred for
      painless hematuria. The CT protocol included unenhanced images, obtained with a
      detector configuration of 16x1.5 mm and pitch of 1.2, nephrographic and excretory
      phase images, obtained with a detector collimation of 16x0.75 mm and pitch of
      1.2. Axial and coronal reformatted images were evaluated. Three-dimensional
      reformation of the excretory-phase images was performed using the volume
      rendering technique. The standard of reference included clinical and imaging
      follow-up, cystoscopic, surgical and histologic findings. In 55 (73%) of 75
      patients, the cause of hematuria was identified on MDCTU; the most common cause
      was urothelial cancer, including seven tumors with a diameter equal or smaller
      than 0.5 cm in diameter. Sixteen-row MDCTU provided satisfactory results in the
      investigation of patients with painless hematuria. The main advantage of the
      technique is its ability to detect uroepithelial malignancies.

PMID- 17021710
TI  - MR-guided breast biopsy and hook wire marking using a low-field (0.23 T) scanner
      with optical instrument tracking.
AB  - The purpose of this study was to evaluate the technical feasibility of MR-guided
      percutaneous breast biopsy (LCNB) and breast hook wire marking in a low-field
      (0.23 T) MRI system with optical instrument tracking. MR-guided core biopsy
      and/or hook wire marking was performed on 13 lesions observable at MR imaging
      only. Seven breast LCNBs and 10 hook wire markings were performed under MR
      guidance on 11 patients. The diagnosis was confirmed by excision biopsy or
      mastectomy in 12 lesions and with histopathological and cytological diagnosis and
      12-month clinical follow-up in one lesion. All lesions seen in the high-field
      scanner were also successfully identified and targeted in the low-field scanner.
      The following procedures were typically technically successful. There were
      difficulties due to unsatisfactory functioning of some core biopsy guns. Detailed
      description of low-field MR guidance and optical tracking in breast biopsies is
      provided. The procedure seems accurate and safe and provides means to obtain a
      histological diagnosis of a breast lesion only seen with MRI. The low-field
      biopsy system is comparable to the high-field MRI system. MR-compatible biopsy
      guns need to be improved.

PMID- 17021711
TI  - Coronary vessel-wall and lumen imaging using radial k-space acquisition with MRI
      at 3 Tesla.
AB  - This study investigates the feasibility of imaging the coronary lumen and vessel
      wall, using MRI with a radial k-space trajectory at 3 T. Such radial trajectories
      offer the advantage of greater vessel sharpness than traditional Cartesian
      trajectories. This field strength offers an increased signal-to-noise ratio (SNR)
      compared with 1.5 T, which compensates for the slight SNR reduction due to the
      radial sequence. Images of the coronary lumen were acquired for seven healthy
      volunteers. In ten volunteers the vessel wall was scanned, with blood suppression
      using oblique-slab adiabatic re-inversion. Scans were performed during free
      breathing, using prospective respiratory navigator-gating. Coronary lumen scans
      had SNR of 16.0+/-1.9 and contrast-to-noise ratio (CNR) of 10.3+/-2.1, showing
      acceptable image quality. Vessel wall images showed good image quality, with mean
      SNR of 16.6+/-2.0/5.8+/-2.8/10.1+/-2.2 for vessel wall/lumen/epicardial fat. The
      wall-blood CNR was 10.7+/-2.7, and wall-fat CNR was 6.5+/-2.5. It is concluded
      that radial gradient-echo imaging at 3 T is a promising method for coronary
      vessel-wall imaging, and is also feasible for imaging the coronary lumen.

PMID- 17021712
TI  - Relationship between the severity of enthesitis and clinical and laboratory
      parameters in patients with ankylosing spondylitis.
AB  - In this study, we evaluated the relationship between the severity of enthesitis
      and outcome of measurement indices, clinical and laboratory parameters in
      patients with ankylosing spondylitis (AS). Thirty-three patients who fulfilled
      the modified New York criteria for AS were included in this study. Patients were
      asked to record the severity of current pain, night pain and morning stiffness on
      a 10-cm visual analogue scale. Stoke Enthesitis Index (SEI) was used to measure
      the severity of enthesitis. Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath
      Ankylosing Spondylitis Metrology Index (BASMI) were calculated. SEI was
      correlated positively only with BASDAI (r = 0.370, P = 0.034). There was no
      relation between SEI and laboratory parameters (Erythrocyte Sedimentation Rate
      and C Reactive Protein). Our data suggest that using an enthesitis index such as
      SEI can be a valuable tool in the evaluation of disease activity in patients with
      AS. However, evaluation of enthesitis severity is based on information given by
      patient and should be combined with objective parameters such as spinal
      measurements when assessing disease activity.

PMID- 17021713
TI  - Combination of intravenous pulses of cyclophosphamide and methylprednizolone in
      patients with systemic sclerosis and interstitial lung disease.
AB  - The purpose of the study was to examine prospectively the efficacy and safety of
      the combination of intravenous pulses of cyclophosphamide and methylprednizolone,
      in the treatment of scleroderma lung disease. Thirteen patients were treated with
      the above combination for up to 24 months. Prior to this treatment, they
      underwent a pulmonary function evaluation and high resolution computed tomography
      (HRCT). Carbon monoxide diffusion lung capacity and forced vital capacity were
      repeated at 6, 12, 24 and 48 months. HRCT was repeated at the end of the
      treatment period, but in between and afterwards in some patients, as well. A
      significant percentage of patients (66.6%) showed stabilization or improvement of
      their pulmonary function. Patients with already seriously compromised function,
      before treatment, were the least likely to exhibit this evolution pattern. There
      was a tendency in some individuals to deteriorate on later evaluations, off
      treatment, although they had stabilized at the end of the treatment. There was
      rather a poor correlation between functional evolution and HRCT appearance.
      Finally, the regimen was well tolerated. Our results suggest that the employed
      combination is safe and effective, mainly in stabilizing the respiratory function
      of the patients. This goal is more realistic when treatment is given before
      significant functional compromise has ensued. The need for long-term
      immunosuppression to maintain the initial favorable response is suggested.

PMID- 17021714
TI  - Adenosine and cytokine levels following treatment of rheumatoid arthritis with
      dipyridamole.
AB  - Adenosine can suppress the release of tumour necrosis factor-alpha (TNF-alpha)
      from activated monocytes and macrophages, and may contribute to the anti
      inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits
      the cellular uptake and metabolism of adenosine and we have, therefore, examined
      the effects of dipyridamole in patients with rheumatoid arthritis in an attempt
      to alleviate their symptoms. Forty patients aged 18-75 years were randomised to
      receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline
      and at monthly intervals for 6 months. Purines were determined by HPLC and
      cytokines by ELISA. After 3 months of treatment there were significant reductions
      in neopterin levels and in the modified Health Assessment Questionnaire score,
      but these were not maintained. Dipyridamole had no effect on disease severity or
      the levels of purine metabolites, interleukin-1beta (IL-1beta), IL-6, TNF-alpha,
      lipid peroxidation products, erythrocyte sedimentation rate or C-reactive
      protein. In conclusion, rheumatoid arthritis patients showed no clinical
      improvement following treatment with dipyridamole for 6 months.

PMID- 17021715
TI  - Primary antiphospholipid nephropathy beginning during pregnancy.
AB  - We describe a 29-year-old pregnant woman at 16 weeks gestation and
      antiphospholipid antibodies who developed nephrotic syndrome with massive
      hematuria. Renal biopsy evidenced chronic glomerular lesions of ischemic nature
      without proliferative changes and immune deposits suggestive of lupus nephritis.
      Anticoagulation was initiated, along supportive measures, and the patient
      recovered completely. This case demonstrates that chronic renal lesions of
      antiphospholipid syndrome may present with marked clinical manifestation
      including hypertension, massive proteinuria and hematuria, resembling the course
      of acute thrombotic microangiopathy and/or lupus nephritis.

PMID- 17021717
TI  - Pantothenate kinase 2 mutation without 'eye-of-the-tiger' sign.

PMID- 17021716
TI  - Harmonic US imaging of appendicitis in children.
AB  - BACKGROUND: Harmonic imaging (HI), a relatively new ultrasound modality, was
      initially reported to be of use only in obese adult patients. HI increases the
      contrast and spatial resolution resulting in artefact-free images, and has been
      shown in adults to significantly improve abdominal sonography. Regarding its
      application in paediatric patients, just a handful reports exist and these do not
      encompass its use in intestinal sonography. OBJECTIVE: To compare the
      sonomorphological image quality of HI and fundamental imaging (FI, conventional
      grey-scale imaging) in the diagnosis of histologically confirmed appendicitis in
      children. MATERIALS AND METHODS: For this prospective comparative study, 50
      children (male/female 25/25; mean age 9.9 years) suspected of having appendicitis
      were recruited. In all patients US examination of the appendix and
      periappendiceal region was performed preoperatively and appendectomy carried out.
      The final diagnosis was based on histological examination of the appendix. Both
      FI and HI were used in the US examination (tissue harmonic imaging, THI; Sonoline
      Elegra, Siemens; 7.5 MHz linear transducer). A detailed comparison of the images
      from FI and HI was performed using a scoring system. The parameters compared
      included delineation of the appendiceal contour, wall, mucosa, contents of the
      appendix and surrounding tissues. Furthermore, periappendiceal findings such as
      mesenteric echogenicity, free fluid, lymph nodes and adjacent bowel wall
      thickening were compared. RESULTS: In 43 children (86%) acute appendicitis was
      histologically confirmed. The inflamed appendix could be depicted in the HI and
      FI modes in 93% and 86%, respectively. HI was found to be significantly better
      for the depiction of the outer contour, wall, mucosa and contents of the appendix
      (P<0.01). This was also true for the demonstration of free fluid, mesenteric
      lymph nodes, adjacent bowel walls and mesenteric echogenicity. CONCLUSION: HI
      should be the preferred modality for scanning the right lower abdomen in
      suspected acute appendicitis. The diagnosis of acute appendicitis can then be
      more definitely ascertained.

PMID- 17021718
TI  - Isolated tubal torsion: a rare cause of pelvic pain at menarche. Sonographic and
      MR findings.
AB  - Isolated torsion of the fallopian tube is a rare clinical entity, especially in
      adolescents and at menarche. The diagnosis is essentially made at laparoscopy or
      at laparotomy because of nonspecific clinical signs. We present a case of
      isolated tubal torsion in a 12-year-old girl a few days after menarche,
      highlighting the sonographic and MR findings. Both techniques demonstrated the
      enlarged and tortuous fallopian tube with normal ovaries and uterus, but MR was
      also able to characterize contained blood and absent vascular supply. Although
      this condition is uncommon it should be considered as a cause of acute pelvic
      pain in adolescents because of the possibility of salvage surgery with early
      diagnosis. Sonography and MRI have a complementary role in this diagnosis.

PMID- 17021719
TI  - Non-enhancing pilocytic astrocytoma of the spinal cord.
AB  - Pilocytic astrocytomas are among the most common intramedullary spinal cord
      tumors in the pediatric age group. The presence of contrast enhancement is a
      major factor used to distinguish these tumors from other spinal cord lesions. We
      present a case of histologically proved non-enhancing intramedullary spinal cord
      pilocytic astrocytoma in a 12-year-old girl. This case represents an exception to
      the conventional wisdom that pediatric spinal neoplasms enhance with
      administration of intravenous contrast material.

PMID- 17021720
TI  - Combination DNA plus protein HIV vaccines.
AB  - A major challenge in developing an HIV vaccine is to identify immunogens and
      delivery methods that will elicit balanced humoral and cell mediate immunities
      against primary isolates of HIV with diverse sequence variations. Since the
      discovery of using protein coding nucleic acids (mainly DNA but also possible
      RNA) as a means of immunization in the early 1990s, there has been rapid progress
      in the creative use of this novel approach for the development of HIV vaccines.
      Although the initial impetus of using DNA immunization was for the induction of
      strong cell-mediated immunity, recent studies have greatly expanded our
      understanding on the potential role of DNA immunization to elicit improved
      quality of antibody responses. This function is particularly important to the
      development of HIV vaccines due to the inability of almost every previous attempt
      to develop broadly reactive neutralizing antibodies against primary HIV-1
      isolates. Similar to the efforts of developing cell mediated immunity by using a
      DNA prime plus viral vector boost approach, the best antibody responses with DNA
      immunization were achieved when a protein boost component was included as part of
      the immunization schedule. Current experience has suggested that a combination
      DNA plus protein vaccination strategy is able to utilize the benefits of DNA and
      protein vaccines to effectively induce both cell-mediated immunity and antibody
      responses against invading organisms.

PMID- 17021722
TI  - The role of diffusion-weighted magnetic resonance imaging in pediatric brain
      tumors.
AB  - OBJECTIVES: Diffusion-weighted imaging (DWI) may enhance the radiographic
      diagnosis of pediatric brain tumors. This study reviews the DWI properties of
      pediatric brain tumors at our institution and examines their relationship to
      tumor grade and type. MATERIALS AND METHODS: The preoperative DWI and apparent
      diffusion coefficient (ADC) characteristics of brain tumors in 41 children were
      compared with histologic diagnosis. Signal characteristics on DWI and ADC maps
      correlated well with tumor grade. High-grade lesions were hyperintense on DWI and
      hypointense on ADC maps. Sensitivity, specificity, positive predictive value, and
      negative predictive value were 70, 100, 100, and 91%, respectively. Signal
      characteristics did not differ among different tumors of the same grade. All
      primitive neuroectodermal tumors showed diffusion restriction whereas none of the
      ependymomas did. CONCLUSIONS: The signal characteristics on DWI and ADC maps
      appeared to be strongly correlated to grade in pediatric brain tumors and they
      may assist with preoperative diagnostic predictions.

PMID- 17021721
TI  - Unraveling the genetics of systemic lupus erythematosus.
AB  - The capacity to locate polymorphisms on a virtually complete map of the human
      genome coupled with the ability to accurately evaluate large numbers (by
      historical standards) of genetic markers has led to gene identification in
      complex diseases, such as systemic lupus erythematosus (SLE or lupus). While this
      is a phenotype with enormous clinical variation, the twin studies and the
      observed familial aggregation, along with the genetic effects now known, suggest
      a strong genetic component. Unlike type 1 diabetes, lupus genetics is not
      dominated by the powerful effect of a single locus. Instead, there are at least
      six known genetic association effects in lupus of smaller magnitude (odds ratio
      <2), and at least 17 robust linkages (established and arguably confirmed
      independently) defining potentially responsible genes that largely remain to be
      discovered. The more convincing genetic associations include the human leukocyte
      antigen region (with multiple genes), C1q, PTPN22, PDCD1, Fc receptor-like 3,
      FcgammaRIIA, FcgammaRIIIA, interferon regulatory factor 5, and others. How they
      contribute to disease risk remains yet to be clarified, beyond the obvious
      speculation derived from what has previously been learned about these genes.
      Certainly, they are expected to contribute to lupus risk independently and in
      combination with each other, with genes not yet identified, and with the
      environment. A substantial number of genes (>10) are expected to be identified to
      contribute to lupus or in its many subsets defined by clinical and laboratory
      features.

PMID- 17021723
TI  - Segmental spinal dysgenesis: report of four cases and proposed management
      strategy.
AB  - INTRODUCTION: Segmental spinal dysgenesis, a rare developmental malformation,
      usually manifests during pregnancy or at birth. The resulting gross spinal
      instability necessitates spinal stabilization, which is inherently challenging in
      neonates. METHODS: We report four cases of segmental dysgenesis: three in the
      thoracolumbar region and one at the cervicothoracic junction. The latter was
      maintained in a custom orthosis that restricted all craniospinal motion while
      allowing routine care. Two neonates underwent surgical stabilization. The fourth
      patient will remain in a brace until 12-14 months old when fusion is planned.
      RESULTS: Fusion with rib autografts failed in the two neonates. One patient has
      been followed for 13 years and is paraplegic. The second patient was lost to
      follow up. The patient with the cervicothoracic dysgenesis maintained normal
      neurologic function until his death at 8 months of cardiac failure. The fourth
      patient is 12 months old and has been maintained in a thoracolumbar orthosis with
      stable neurologic function. CONCLUSION: Several factors contribute to the
      challenge of creating a stable fusion in neonates. Incomplete ossification of the
      vertebral bodies and poor results with allograft materials restrict fusion
      options. Neurologic deficits often prevent ambulation and decrease the axial
      loading forces that enhance fusion. To allow children to grow and develop, we
      advocate rigid spinal immobilization for 12-18 months before spinal fusion
      (preferably, rib or fibular autograft). Given the already narrow spinal canal,
      the use of instrumentation is controversial. We advocate the use of
      instrumentation in infants only when a sound construct cannot be obtained with
      the graft alone.

PMID- 17021724
TI  - The child with the varus foot.

PMID- 17021725
TI  - Chiari I malformation, caudal regression syndrome, and Pierre Robin Syndrome: a
      previously unreported combination.
AB  - CASE: The authors report a child born with a constellation of findings including
      Chiari I malformation, Pierre Robin syndrome, and caudal regression syndrome. In
      addition, this child was found to have a fatty-infiltrated filum terminale and a
      low conus medullaris. DISCUSSION AND CONCLUSION: In isolation, the Chiari I
      malformation has been reported in patients with caudal regression and Pierre
      Robin syndrome. Speculation has been given to the possibility of a common insult
      to early mesodermal development and each of these pathological entities. To our
      knowledge, this is the first report of a single patient that possessed all three
      entities (i.e., Chiari I malformation, Pierre Robin syndrome, and caudal
      regression syndrome). Further case reports as this may shed light on the
      dysembryology that results in each of these diagnoses.

PMID- 17021726
TI  - Unusual split cord with neurenteric cyst and cerebellar heterotopia over spinal
      cord.
AB  - OBJECTIVE: To report a case of splitting of a cord, which could neither be
      classified as type I nor type II according to Pang's classification. The child
      had associated neurenteric cyst and cerebellar tissue heterotopia. CASE REPORT: A
      3-year-old girl presented with a tuft of hair and dermal sinus at her upper
      dorsal spine. She had splitting of cord into two halves by two intradural horny
      osseocartilaginous spurs leaving a gap of 3 mm in between (two spurs and two
      halves of cords). A neurenteric cyst was seen passing from the anterior to
      posterior aspect of the cords through this gap. An associated heterotopic
      cerebellar tissue mass was encountered over the dorsum of cord proximal to
      splitting. The dermal sinus, neurenteric cyst, and spurs were excised to detether
      the cord. The heterotopic tissue was biopsied. The child had no neurological
      deficit at 2.5 years follow-up. CONCLUSION: An unusual splitting of cord by
      unusual spurs may leave a gap between two spurs and two halves of cords to pass a
      neurenteric cyst. Rarely, heterotopic tissue may be associated with split cord
      syndrome. A dermal sinus may lead into underlying neurenteric cyst (rather than
      dermoid).

PMID- 17021727
TI  - Diffuse high-grade gliomas as second malignant neoplasms after radio-chemotherapy
      for pediatric malignancies.
AB  - OBJECTS: Diffuse high-grade gliomas are known to develop in children after
      cranial irradiation for other malignancies. Here, clinicopathological
      characteristics are outlined. METHODS: Nine children received cranial irradiation
      and chemotherapy for medulloblastoma (n=2) or acute lymphoblastic leukemia (n=7).
      They developed a high-grade glioma 7-14 years thereafter. Clinical charts,
      radiologic findings, and pathologic specimens were reviewed. Archival material
      was stained immunohistochemically. CONCLUSION: Gliomas evolving as second
      malignant neoplasms show peculiarities and differ in some aspects from their
      "spontaneous" counterparts. Most are supratentorial, contrast-enhancing, space
      occupying lesions. They are composed mainly of small undifferentiated cells,
      which are mainly negative for glial fibrillary acidic protein and positive for
      microtubule associated proteins 2 (MAP2). Epidermal growth factor receptor
      labeling could not be detected in any of them. Ki67-labeling was usually high,
      whereas p53- and h-ras p21-staining was variable. The median survival was only 12
      months despite intensive treatment.

PMID- 17021728
TI  - Long-term outcome and neurologic development after endoscopic third
      ventriculostomy versus shunting during infancy.
AB  - INTRODUCTION: Infants with obstructive hydrocephalus who were under 9 months old
      were initially treated by neuroendoscopic third ventriculostomy (ETV) after
      evaluation with magnetic resonance imaging (MRI). The clinical course and long
      term outcome of these infants were examined. The outcome was also compared with
      that of similar infants who received ventriculoperitoneal shunting. METHODS: The
      patients were divided into three groups based on MRI findings: Group I was made
      up of six patients in whom mainly the frontal horns of the lateral ventricles
      were enlarged and the morphology of the cerebral cortex was normal; group II was
      made up of 13 patients in whom the entire lateral ventricle was enlarged
      bilaterally and the morphology of the cerebral cortex relatively normal; and
      group III was made up of six patients in whom the entire lateral ventricle was
      markedly enlarged bilaterally and there was periventricular leakage of
      cerebrospinal fluid. RESULTS: In group I, two patients were treated
      conservatively and four patients were treated with ETV. All of the patients in
      this group showed virtually normal development at 4 years of age. In group II,
      development was still delayed in six patients at 1 year after ETV, and two of
      these patients underwent shunting. All of the patients in this group showed near
      normal development at 5 to 6 years of age. In group III, all of the patients
      underwent shunting within 1 year after ETV because there was no appreciable
      improvement of development at 6 months after the initial procedure. CONCLUSIONS:
      In infants with obstructive hydrocephalus in whom the cerebral cortex is intact,
      adequate development can be achieved with ETV alone, although catch-up tends to
      be slow. In infants in whom cerebral development is inadequate or in whom the
      cerebrum has already been affected by hydrocephalus, sufficient improvement of
      development cannot be achieved with ETV alone, even if the intracranial pressure
      is controlled. It seems that early shunting is more useful for achieving cerebral
      recovery in this patient group.

PMID- 17021729
TI  - Evaluation of the lumbar and ventricular infusion test in the diagnostic strategy
      of pediatric hydrocephalus and the therapeutic implications.
AB  - AIM: To evaluate the infusion test as a diagnostic tool behind the choice of
      intervention in pediatric hydrocephalus. MATERIALS AND METHODS: Intracranial
      pressure (ICP) measurement and infusion test were performed intraventricularly,
      by lumbar route, or combined in 40 consecutive children as a part of the standard
      diagnostic program in 1996-1999. RESULTS: The median age was 18.5 months, ranging
      from 2 weeks to 13 years. In the subgroup of patients with radiological
      aqueductal stenosis (N=14), mean lumbar/intraventricular ICP was 13 (3-35)/10 (2
      27). Mean lumbar/ventricular R(out) were 18 (4-49)/17 (6-37). For patients with
      radiological communication between the third and fourth ventricles (N=14), the
      mean lumbar/intraventricular ICP was 11 (7-17)/9 (1-16). Mean lumbar/ventricular
      R(out) were 8 (3-11)/8 (4-12). A total of 13 patients had a shunt insertion, 10
      had an endoscopic third ventriculostomy (ETV), 5 had endoscopic fenestration of a
      cyst, and 12 had no surgery. Of the patients initially treated with EVT, 50% had
      a shunt insertion shortly after. For communicating hydrocephalus, 75% of the
      patients initially not operated based on normal R(out) values ended up having a
      shunt insertion. DISCUSSION: R(out) has doubtful value as an indicator for
      conducting an operation or not and in the choice between EVT and shunt in
      children. This should be interpreted in the light of a growing understanding of
      hydrocephalus on a molecular level.

PMID- 17021730
TI  - Birth trauma and development of growing fracture after coronal suture disruption.
AB  - INTRODUCTION: A growing fracture is a rare complication of skull fractures
      characterized by progressive diastatic enlargement of the fracture line. Growing
      skull fractures related to birth trauma were only occasionally reported. As far
      as we know, only one previous case of a neonatal growing fracture secondary to
      coronal suture disruption has been reported. CASE REPORT: We present the case of
      a full-term infant born after a nontraumatic, forceps-assisted spontaneous
      delivery, who developed an increasing cystic swelling over the left
      frontoparietal area that crossed over coronal and sagittal sutures. The lesion
      was initially misinterpreted as cephalhematoma. Clinical and radiological follow
      up established the correct diagnosis of leptomeningeal cyst. OUTCOME: The
      collection was initially tapped. Surgical treatment was undertaken thereafter,
      consisting of decompression and resection of the cyst and dural repair. Two
      months after follow-up, the patient remains asymptomatic and the porencephalic
      cavity remains isolated from the extradural space, with no evidence of new fluid
      collections.

PMID- 17021731
TI  - An unusual case of cervical clear-cell meningioma in pediatric age.
AB  - INTRODUCTION AND BACKGROUND: A 4-year-old girl was admitted with complaints of
      diplegia, right lower limb monoplegia, and left lower limb monoparesia. Cervical
      magnetic resonance imaging revealed an intradural-extramedullary tumor at the
      level of C1-C2. The tumor was resected totally. Histopathologic diagnosis
      revealed clear-cell meningioma. DISCUSSION: Intraspinal clear-cell meningioma
      (ICCM) is a rare aggressive variant of meningioma. There are only 25 cases
      reported to date, and only 13 of them are in pediatric age group. Of these 25
      ICCM cases, only two are at cervical region. This report is the first ICCM case
      at upper cervical region (C1-C2) in both adult and pediatric age populations.

PMID- 17021732
TI  - A novel brainstem tumor model: functional and histopathological characterization.
AB  - INTRODUCTION: Diffuse pontine gliomas remain a challenging and frustrating
      disease to treat. The survival rates for these high-grade brainstem tumors (BSTs)
      is dismal and optimal therapy has yet to be determined. The development of a
      satisfactory brainstem tumor model is necessary for testing new therapeutic
      paradigms that may prolong survival. MATERIALS AND METHODS: We report the
      surgical technique, functional testing, and histopathological features of a novel
      brainstem tumor model in rats. Female Fischer 344 rats (n=45) were randomized to
      receive an injection of either 3 microl of 9L gliosarcoma cells (100,000 cells,
      n=), 3 microl of F98 glioma cells (100,000 cells, n=10), or 3 microl of medium
      (Dulbecco's modified eagle medium) into the pontine tegmentum. Using a cannulated
      guide screw system, implanted in the skull of the animal, we injected each group
      at coordinates 1.4 mm right of the sagittal and 1.0 mm anterior of the lambdoid
      sutures, at a depth of 7.0 mm from the dura. The head was positioned 5 degrees
      from horizontal before injection. The rats were post-operatively evaluated for
      neurological deficits using an automated test. Kaplan-Meier curves were generated
      for survival and disease progression, and brains were processed postmortem for
      histopathology. RESULTS AND DISCUSSION: 9L and F98 tumor cells grew in 100% of
      animals injected and resulted in a statistically significant mean onset of
      hemiparesis of 16.5+/-0.56 days (P=0.001, log-rank test), compared to animals in
      the control group which lacked neurological deficits by day 60. The animals with
      tumor cells implanted demonstrated significant deterioration of function on the
      automated rod testing. Animals in the control group showed no functional or
      pathological signs of tumor. Progression to hemiparesis was consistent in all
      tumor-injected animals, with predictable onset of symptoms occurring
      approximately 17 days post-surgery. The histopathological characteristics of the
      9L and F98 BSTs were comparable to those of aggressive human BSTs. CONCLUSION:
      The establishment of this animal tumor model will facilitate the testing of new
      therapeutic paradigms for the treatment of BSTs.

PMID- 17021733
TI  - Multifocal Langerhans cell histiocytosis of the pediatric spine: a case report
      and literature review.
AB  - CASE REPORT: An 11-month-old boy presented with a 3-month history of lower
      extremity weakness. CT and MRI of the spine revealed an enhancing epidural mass,
      extending from T1 through T5 and exiting through multiple foramina. The largest
      extraspinal extent was located at the T3 vertebral level and was accompanied by
      complete T3 vertebral collapse. A second lytic lesion at the L2 vertebral body
      without an obvious enhancing mass was also noted. Open biopsy and decompression
      of the spinal cord were performed, and histopathological analysis revealed a
      mixed inflammatory lesion with abundant S-100 and CD1a immunoreactive Langerhans
      cells consistent with the diagnosis of Langerhans cell histiocytosis (LCH).
      DISCUSSION: The authors present a very rare pediatric case of spinal LCH causing
      spinal cord compression. Possible clues to early detection, consideration of
      differential diagnoses, and a brief literature review are presented.

PMID- 17021734
TI  - Invasive intracerebral schwannoma mimicking meningioma in a child.
AB  - CASE REPORT: An 8-year-old boy presented to the emergency department after a
      generalized tonic-clonic seizure that lasted for 5 min. Magnetic resonance
      imaging showed a 2x2 cm, intraaxial, contrast-enhanced cortical lesion in the
      posterior right frontal lobe. On several images the lesion appeared to be dural
      based and was presumed to be a meningioma. The patient was placed on dilantin and
      returned 1 month later for elective surgical resection. OUTCOME: At surgery, a
      rim of intact pia was identified between the dura and the tumor. Although initial
      frozen-section analysis was consistent with meningioma, subsequent
      immunohistochemical staining and review at an outside institution established the
      diagnosis of intracerebral schwannoma. The patient's postoperative course was
      uncomplicated and he remains seizure-free with no sign of recurrence at 18
      months. CONCLUSION: Intracerebral schwannomas are uncommon cortical lesions in
      children. Imaging characteristics alone can be misleading; neuropathological
      support is essential for accurate diagnosis.

PMID- 17021735
TI  - Improvement in the quality of life using both Bianchi's procedure and the closure
      of a jejunostomy in a case with short bowel syndrome.
AB  - In cases with short bowel syndrome (SBS), intestinal adaptation often requires a
      long time. In addition, the quality of life in SBS is not especially good due to
      some complications, including growth impairment, severe diarrhea, complications
      of parenteral nutrition (PN), and so on. We herein report an adolescent boy with
      SBS secondary to midgut volvulus. He suffered mainly from both severe high output
      syndrome, which caused a large amount of enteric fluid to flow out from the
      jejunostomy, and growth impairment, although PN continued after the occurrence of
      SBS. As a result, he thereafter could not continue his daily school life.
      Therefore, he was introduced to our department at 6 months after the operation. A
      closure of the jejunostomy combined with longitudinal intestinal lengthening
      using Bianchi's procedure was performed. Thereafter, the above-described symptoms
      disappeared. He was discharged and thereafter was again able to attend school
      with an improvement in his growth within 2 months after the second operation.
      Home PN was discontinued at 15 months after the second operation. Based on our
      experience, in cases of SBS without intestinal functional disorder, an early
      closure of the jejunostomy combined with Bianchi's procedure might therefore
      possibly lead to an early improvement in the complications related to SBS.

PMID- 17021736
TI  - Congenital diaphragmatic hernia: onset of respiratory distress and size of the
      defect: analysis of the outcome in 104 neonates.
AB  - The purpose of this study was to evaluate the outcome in neonates with congenital
      diaphragmatic hernia (CDH) either presenting within the first 24 h of life or
      diagnosed prenatally. The study was particularly focused on the time of onset of
      respiratory distress and on the use of the Gore-Tex (GT) patch for diaphragmatic
      reconstruction. Records of 104 neonates with CDH were retrospectively reviewed.
      The data were analyzed by ANOVA, Kruskal-Wallis test or chi (2) test as
      appropriate. The result showed that the overall survival rate was 73.1% (76/104).
      Survival of operated neonates was 91.6% (76/83). Postnatally diagnosed neonates
      with the onset of respiratory distress within the first minute of life survived
      in 67%, with the onset between 2 and 10 min survived in 89%, whilst neonates with
      the onset of respiratory distress after l0 min survived in 100% (P = 0.007).
      Birth weight, gestational age, time of onset of respiratory distress and Apgar
      score significantly differed between survivors and nonsurvivors. Primary closure
      of the diaphragmatic defect was performed in 62 patients while the GT patch was
      used in 21 patients. The survival of patients with a large defect treated with a
      GT patch was lower (76.2 vs. 96.8%, P = 0.003). There was only one case of
      recurrence in our series with the GT patch. Survival depends on the time of onset
      of respiratory distress and size of the defect, both of which correlate with the
      degree of pulmonary hypoplasia. The term high-risk CDH is appropriate only for
      children with respiratory distress within the first 10 min of life and those
      diagnosed prenatally. The GT patch is a suitable material for the diaphragmatic
      reconstruction; we suppose that the recurrence is caused by incorrect attachment
      of the patch to the thoracic wall.

PMID- 17021737
TI  - The role of sphincteroplasty in adverse effect of anomalous pancreaticobiliary
      duct union in an animal model.
AB  - Anomalous union between the pancreatic and biliary systems (APBDU) has been
      reported to produce choledochal cyst. The aim of this experiment was to evaluate
      the role of sphincteroplasty to adverse effect of APBDU in an animal model.
      Twelve mongrel puppies were randomly divided into a control group (n = 5) and an
      experimental group (n = 7). A well-established model of APBDU was produced in
      both groups. Transduodenal sphincteroplasty was performed only on the
      experimental group. For all animals, serial chemical analyses of serum were
      performed, and biliary tree sizes were measured by magnetic resonance
      cholangiography 2.5 months after the experimental surgery. At the time of animal
      sacrifice, 3 months after the experimental surgery, operative cholangiography was
      performed, and bile juice and tissues were obtained for chemical analysis and
      histologic examination. Dilatation of the bile duct and thickening of the wall of
      the bile duct were observed less frequently in the experimental group than in the
      control group. There were no significant differences found in pancreatic enzyme
      activity in the bile juice between the two groups. Denudation of the mucosa was
      the predominant mucosal change seen in the experimental group, while epithelial
      hyperplasia was the predominant mucosal change found in the control group. Our
      experiment shows that sphincteroplasty is not effective to prevent the
      pancreaticobiliary reflux, but may be effective to reduce the degree of both bile
      duct dilatation and mural thickening in the APBDU puppy model.

PMID- 17021738
TI  - The risk of medullary thyroid carcinoma in patients with Hirschsprung's disease.
AB  - Hirschsprung's disease (HD) can be associated with the development of
      neuroendocrine tumours such as medullary thyroid carcinoma (MTC). The RET proto
      oncogene is the major gene responsible for both HD and MTC. Mutations in exon 10
      (codons 609, 611, 618, 620) were found in patients with co-occurrence of HD and
      MTC. The aim of the study was to screen the MTC risk in patients with HD. The
      prospective and retrospective genetic analyses comprised 56 HD patients (41
      males, 15 females, aged 0-47). The prospective subgroup of patients consisted of
      34 patients (25 boys, 9 girls) operated on between June 2003 and December 2005.
      The retrospective subgroup comprised 22 patients (16 boys, 6 girls) of 194
      patients who were operated on between December 1979 and May 2003, non
      systematically chosen preferably for total colonic aganglionosis (TCA). DNAs were
      isolated from blood and resected segments of aganglionic bowel. The HD patients
      and nine available family members (2 HD) were tested for RET mutations in exons
      10, 11, 13, 14, 15 and 16. Direct double-stranded fluorescent sequencing revealed
      typical germline heterozygous MTC risk RET mutations in 3/56 (5.4%) female HD
      patients: Cys609Tyr, Cys620Arg (both exon 10) and Tyr791Phe (exon 13). Two of
      these patients had TCA and one patient had classical type of HD. One TCA patient
      developed clinical stage of MTC and underwent total thyroidectomy (TTE). The
      other two RET positive HD patients (aged 7 and 25 years) are screened for
      calcitonin level and they are without TTE till now. Two family members (mothers
      of TCA patients) with detected RET mutation underwent prophylactic TTE with MTC
      finding. Results showed the benefit of systematic RET mutation screening in HD
      patients in order to identify the risk of MTC in preclinical stage of the disease
      in patients with HD and their family members. We recommend to investigate not
      only exon 10 but also exon 13.

PMID- 17021739
TI  - Biliary atresia associated with multiple unrelated anomalies: what about it?
AB  - The prognosis of extrahepatic biliary atresia (EHBA) and multiple apparently not
      linked anomalies has never been disclosed. We reported a rare case affected by
      biliary, anorectal and esophageal atresia, and collected the uncommon
      associations of EHBA with multiple unrelated congenital defects to make known the
      prognosis. An elevated rate of hepatic failure despite surgery and an early poor
      outcome were found in the above-mentioned associations. A liver transplantation
      at the first months of life could be considered to improve outcome.

PMID- 17021740
TI  - Could adding magnesium as adjuvant to ropivacaine in caudal anaesthesia improve
      postoperative pain control?
AB  - Recently, most studies reported magnesium as a N-methyl-D-aspartate receptor
      antagonist and its analgesic and perioperative anaesthetic effects have been
      discussed with central desensitization pathway. We investigated the effects of
      caudal ropivacaine plus magnesium and compared with ropivacaine alone on
      postoperative analgesia requirements. After hospital ethic committee's consent,
      60 patients (ASA I-II, 2-10 years old) who had lower abdominal or penoscrotal
      surgery were enrolled in the study. After general anaesthesia induction, caudal
      blockage was applied. Patients were randomly assigned in two groups. Ropivacaine
      0.25% was administered to Group R (n=37), ropivacaine 0.25% plus 50 mg magnesium
      to Group RM (n=23) in 0.5 ml kg-1 volume. Postoperative analgesia level was
      recorded at 15 min and 1, 2, 3, 4, 6 h by using Paediatric Objective Pain Scale
      (POPS) and The Children's Hospital of Eastern Ontoria Pain Scale (CHEOPS).
      Postoperative motor blocks were evaluated with Modified Bromage Motor Block
      Scale. According to demographic characteristics, there were no significant
      differences between the two groups (P>0.05). POPS, CHEOPS, Bromage Motor Scales,
      analgesia duration and adverse effects were similar in Group R and Group RM. It
      has been shown that addition of magnesium as an adjuvant agent to local
      anaesthetics for caudal analgesia has no effect on postoperative pain and
      analgesic need.

PMID- 17021741
TI  - Oesophageal substitution with free and pedicled jejunum: short- and long-term
      outcomes.
AB  - In children, the indications for oesophageal substitution are principally, long
      gap oesophageal atresia (OA), severe anastomotic disruption following primary
      repair of OA and severe caustic or peptic strictures. We present an outcome
      review of eight cases who underwent oesophageal substitution with jejunum at our
      institution between 1986 and 2001. The purpose of this study was to evaluate our
      experience with free/pedicled jejunal grafts and its long-term outcome as an
      oesophageal substitute. Operative and postoperative outcome with free and
      pedicled jejunal grafts in four cases of pure OA, two cases of OA and distal
      tracheo-oesophageal fistula (TOF), one patient with a high retrolaryngeal
      oesophageal web and one case of severe caustic oesophageal stricture. Six
      patients had an oesophagostomy and a gastrostomy fashioned previously. Eleven
      free jejunal grafts were performed in six patients (three intraoperative redo
      interpositions for immediate graft loss, three separate grafts in one patient and
      two free grafts in two patients). One patient's pedicled jejunal graft proximally
      required microvascular anastomosis while the other had a pedicled graft without
      microvascular anastomosis. Early postoperative complications included four upper
      anastomotic leaks (three free grafts, one pedicled with microvascular support),
      pneumothorax requiring prolonged ventilation and Horner's syndrome. Recurrent
      laryngeal nerve injury occurred in the patient who had a high retrolaryngeal
      oesophageal web. During follow up (5-18 years) late complications of upper
      anastomotic stricture in four patients and graft redundancy with subsequent
      kinking of the lower anastomosis were observed in one patient. Three patients
      established a complete oral diet; a further three patients relied on supplemental
      gastrostomy feeds and one patient is entirely gastrostomy fed. There were two
      late deaths, one from aspiration and the other from a severe asthmatic attack (5
      and 7 months postoperatively, respectively). Our results indicate that there are
      significant complications related to the use of free jejunal grafts. Early
      recognition and treatment are of paramount importance in the ultimate achievement
      of a successful technical outcome.

PMID- 17021742
TI  - Intussusception in children: 11-year experience in Vladivostok.
AB  - Idiopathic intussusception is an important abdominal emergency in infancy and
      childhood. The nonoperative management by air enema has always been the standard
      of care in Russia. Our purpose is to assess our reduction rate and the rate of
      complications. We performed a retrospective analysis of all intussusception cases
      seen at the Department of Paediatric Surgery from 1994 to 2005. The data obtained
      included age, sex, clinical presentation, diagnostic procedures, mode of
      treatment, and results. Patients included 280 children from 1 month to 14 years
      of age. Eighty-one percent of children were under age 1 year old, 61% were boys.
      The duration of symptoms before treatment was less than 18 h in 65%, 18-24 h in
      21%, and more than 24 h in 14% of patients. The successful reduction rate was
      86.1%. One patient with a duration of symptoms more than 24 h experienced colon
      perforation. Thirty-nine patients underwent surgery and, among these,
      abnormalities in the intestinal wall required resection in 12 cases. An
      association between the duration of symptoms and the outcome of the non-surgical
      treatment was present; non-surgical reduction was successful in 97.3% in the
      group with the duration of symptoms less than 18 h, 86.4% in 12-24 h, and 33.3%
      in more than 24 h. Air enema is a safe and effective approach for uncomplicated
      intussusception reduction with a high success rate, but the duration of symptoms
      directly increases the complication rate.

PMID- 17021743
TI  - Conservative treatment of infantile hypertrophic pyloric stenosis with
      intravenous atropine sulfate does not replace pyloromyotomy.
AB  - Pyloromyotomy as described by Weber and Ramstedt has been the standard therapy
      for infantile hypertrophic pyloric stenosis since the 1960's and conservative
      therapy has been abandoned. The objective of this study was to test the
      effectiveness of systemic atropine applied intravenously for 7 days as a
      conservative therapeutic strategy and as an alternative to primary operation.
      Forty-two consecutive term infants with infantile hypertrophic pyloric stenosis
      were enrolled in the study over a period of 5 years. After confirmation of the
      diagnosis they all received intravenous atropine at a dose of 0.04 mg/(kg day)
      and increased by 0.01 mg/(kg day) up to 0.12 mg/(kg day), given as 6-8 single
      doses per/day. Nine pairs of parents requested that their child should be
      operated before completing the 7 days of medical therapy. Surgery was necessary
      in 8 of the remaining 33 infants (24,.2%) who did not improve after 7 days of
      conservative treatment. Successful treatment with i.v. atropine sulfate was
      achieved only in 25/33 term infants at an average maximal dose of 0.11 mg/(kg
      day), without any major side effects. Intravenous atropine sulfate has been
      considered as a potential alternative therapeutic strategy in the treatment of
      infantile hypertrophic pyloric stenosis. Clinical improvement however was often
      not seen before the 6th or 7th day of intravenous treatment. A success rate for
      the conservative approach of only 75% at day 7 in our study does not favour
      atropine therapy, in view of success rates above 95% with surgical repair.

PMID- 17021744
TI  - Right-sided Bochdalek hernia with intrathoracic kidney.
AB  - Bochdalek hernias are usually congenital and are seen with much greater frequency
      on the left side. Intrathoracic kidney is a very rare congenital anomaly, with
      only about 50 cases reported in the world literature. The incidence of
      intrathoracic kidney with Bochdalek hernias was reported to be less than 0.25%. A
      22-month-old boy was admitted to our clinic with recurrent pulmonary infections.
      A chest X-ray, intravenous urogram, computed tomography, and magnetic resonance
      angiography revealed a right-sided Bochdalek hernia with dilated colon loops and
      right kidney within right hemithorax. Under a thoracotomy, a direct closure of
      the hernia was performed after the colon and kidney were returned to the abdomen.
      We report the second case, which has a diagnosis of a right Bochdalek hernia with
      intrathoracic kidney. Clinical correlations among this unusual combination are
      discussed.

PMID- 17021745
TI  - Distinct molecular patterns based on proximal and distal sporadic colorectal
      cancer: arguments for different mechanisms in the tumorigenesis.
AB  - BACKGROUND AND AIMS: Colorectal cancer (CRC) ranks as the fourth most frequently
      diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic
      flexure show differences in epidemiologic incidence, morphology, and molecular
      alterations, suggesting the existence of two categories of CRC based on the site
      of origin. The aim of the present work is to investigate the histological and
      molecular differences between CRCs located proximally and distally to the splenic
      flexure, and their potential involvement in tumor prognosis and therapeutic
      strategies. METHODS: We evaluated 120 patients affected by sporadic CRC for
      clinicopathologic features, microsatellite instability (MSI), loss of
      heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated
      for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining. RESULTS: The mucinous
      histotype was more frequent in the proximal than in the distal CRCs (p<0.004).
      The frequency of MSI phenotype was higher in proximal than in distal tumors
      (p<0.001); moreover, reduced or absent hMlh1, Fhit, p27 immunohistochemical
      expressions were more frequent in proximal than in distal tumors (p<0.001 and
      0.01 for p27). In contrast, the frequency of LOH in 18q was higher in distal than
      in proximal tumors (p=0.002). No significant differences were observed between
      proximal and distal tumors in the frequency of LOH in 8p and altered expression
      of hMsh2 and p53 protein. CONCLUSION: These different features may reflect
      different genetic pathways of carcinogenesis and support the hypothesis of a
      different mechanism of cancer development between the proximal and the distal
      colon, with potential implications in the therapeutic approach.

PMID- 17021746
TI  - Different matrix micro-environments in colon cancer and diverticular disease.
AB  - BACKGROUND AND AIMS: The extracellular matrix and the interactive signalling
      between its components are thought to play a pivotal role for tumour development
      and metastasis formation. An altered matrix composition as potential underlying
      pathology for the development of colorectal cancer was hypothesized. METHODS: In
      a retrospective study of patients with colon cancer, the extracellular matrix in
      tumour-free bowel specimen was investigated in comparison with non-infected bowel
      specimen from patients operated on for colonic diverticulosis. The following
      matrix parameters with known associations to tumour formation, cell
      proliferation, invasion and metastasis were analysed by immunohistochemistry and
      quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1,
      p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles
      and correlations were calculated. RESULTS: The comparison of the two groups
      revealed a significantly decreased immunostaining for CD117 and TGF-beta in the
      cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively),
      whereas PAI scores were significantly higher than in patients with diverticular
      disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix
      parameters indicated pronounced differences between tumour-free tissue in cancer
      patients compared with patients with diverticular disease. CONCLUSIONS: Our
      results indicate distinct differences in the colonic tissue architecture between
      cancer patients and patients with diverticulitis that support the notion of an
      altered matrix composition predisposing to the development of colon cancer.

PMID- 17021748
TI  - Stapled transanal rectal resection versus stapled anopexy in the cure of
      hemorrhoids associated with rectal prolapse. A randomized controlled trial.
AB  - PURPOSE: A remarkable incidence of failures after stapled axopexy (SA) for
      hemorrhoids has been recently reported by several papers, with an incomplete
      resection of the prolapsed tissue, due to the limited volume of the stapler
      casing as possible cause. The stapled transanal rectal resection (STARR) was
      demonstrated to successfully cure the association of rectal prolapse and
      rectocele by using two staplers. The aim of this randomized study was to evaluate
      the incidence of residual disease after SA and STARR in patients affected by
      prolapsed hemorrhoids associated with rectal prolapse. METHODS: Sixty-eight
      patients were selected on the basis of validated constipation and continence
      scorings, clinical examination, colonoscopy, anorectal manometry, and
      defecography and randomized: 34 underwent a SA and 34 a STARR operation. The
      operated patients were followed-up with clinical examination, visual analog scale
      for postoperative pain, a satisfaction index, and defecography. RESULTS: At a
      mean follow-up of 8.1+/-2.0 and 7.9+/-1.8 months for the SA and STARR groups,
      respectively, the incidence of residual disease was significantly higher in the
      first group (29.4 vs 5.9 in the STARR group, p=0.007), while a significantly
      lower incidence of residual skin-tags was found after STARR (23.5% vs 58.8 after
      SA, p=0.03). All patients with residual disease showed prolapsed tissue over half
      the length of the anal dilator at the time of the operation. Operative time and
      incidence of transient fecal urgency were significantly higher in the STARR group
      (with p=0.001 and 0.08, respectively), while SA was followed by a significantly
      higher incidence of poor results at the overall patient satisfaction index
      (p=0.04). No significant differences were found in hospital stay, operative
      complications, postoperative pain, time to return to normal activity, continence,
      and constipation scores. All the defecographic parameters significantly improved
      after STARR, while SA was followed only by a trend to a reduction of rectal
      prolapse. CONCLUSIONS: STARR provides a more complete resection of the prolapsed
      tissue than SA in patients with association of prolapsed hemorrhoids and rectal
      prolapse with equal morbidity and significantly lower incidence of residual
      disease and skin-tags. The anal dilator can be used for selecting the surgical
      technique.

PMID- 17021747
TI  - Rectal prolapse.
AB  - INTRODUCTION: Rectal prolapse, or procidentia, is defined as a protrusion of the
      rectum beyond the anus. It commonly occurs at the extremes of age. Rectal
      prolapse frequently coexists with other pelvic floor disorders, and patients have
      symptoms associated with combined rectal and genital prolapse. Few patients, a
      lack of randomized trials and difficulties in the interpretation of studies of
      anorectal physiology have made the understanding of this disorder difficult.
      METHODS OF TREATMENT: Surgical management is aimed at restoring physiology by
      correcting the prolapse and improving continence and constipation, whereas in
      patients with concurrent genital and rectal prolapse, an interdisciplinary
      surgical approach is required. Operation should be reserved for those patients in
      whom medical treatment has failed, and it may be expected to relieve symptoms.
      Numerous surgical procedures have been suggested to treat rectal prolapse. They
      are generally classified as abdominal or perineal according to the route of
      access. However, the controversy as to which operation is appropriate cannot be
      answered definitively, as the extent of a standardized diagnostic assessment and
      the types of surgical procedures have not been identified in published series.
      LITERATURE REVIEW: This review encompasses rectal prolapse, including aetiology,
      symptoms and treatment. The English-language literature about rectal prolapse was
      identified using Medline, and additional cited works not detected in the initial
      search were obtained. Articles reporting on prospective and retrospective
      comparisons and case reports were included.

PMID- 17021750
TI  - Pull-through procedure as treatment for coloanal anastomotic dehiscence following
      laparoscopic total mesorectal excision.

PMID- 17021749
TI  - p53 protein accumulation as a prognostic marker in sporadic colorectal cancer.
AB  - BACKGROUND AND AIMS: p53 protein plays a crucial role in the pathogenesis of a
      large number of malignancies. In this study, our goal was to elucidate the
      prognostic role of p53 overexpression and its relationship to clinicopathological
      variables in colorectal cancer. MATERIALS AND METHODS: Between 1999 and 2004,
      surgical specimens of 258 patients who received surgical treatment for colorectal
      cancer at the Veterans General Hospital, Taipei were collected. p53 expression in
      tumor tissue was evaluated by immunohistochemical analysis using the human p53
      specific mouse monoclonal antibody, PAb 1801. RESULTS: Of the 258 patients, 97
      (37.6%) had overexpression of p53 in tumor tissues. The accumulation of p53
      protein in tumor tissues did not correlate with age, gender, preoperative serum
      carcinoembryonic antigen (CEA) level, mucin content, nodal status, and tumor
      stage. A statistically significant correlation was found between p53
      overexpression and location of the tumor in the rectum (p=0.038). Well to
      moderately differentiated tumors had significantly higher frequency of p53
      overexpression than poorly differentiated tumors (40.0 vs 20.0%, p=0.050). Each
      patient was followed up for a minimum of 2 years (median 35 months). In
      univariate analysis, 3-year cancer-specific survival rate was significantly
      higher in patients with tumor p53 overexpression (88.2%) than in patients without
      overexpression (log rank test, p=0.037). However, in multivariate analysis, the
      tumour node metastasis stage remained the most significant independent prognostic
      factor. CONCLUSION: The accumulation of p53 protein might have a favorable
      prognostic value in colorectal cancer, but it is not an independent prognostic
      factor.

PMID- 17021751
TI  - Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina
      bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido
      nigral degeneration.
AB  - We report the case of a 54-year-old woman with mental retardation who developed
      frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium.
      She presented with dementia at age 48, and motor neuron signs developed at age
      53. She had no family history of dementia or ALS. Postmortem examination
      disclosed histopathological features of ALS, including pyramidal tract
      degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive
      for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this
      case included severe neuronal loss in the substantia nigra and medial globus
      pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well
      preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal,
      temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus
      coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum,
      hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic
      plaques were found. Tau immunostaining demonstrated many pretangles rather than
      NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal
      cortices. This glial tau pathology predominantly developed in the middle to deep
      layers in the primary motor cortex, and was frequently associated with the walls
      of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific
      antibodies against tau, respectively. Although the pathophysiological
      relationship between tau pathology and the selective involvement of motor
      neurons, substantia nigra, and globus pallidus was unclear, we considered that it
      might be more than coincidental.

PMID- 17021752
TI  - D2-40 functions as an effective chondroid marker distinguishing true chondroid
      tumors from chordoma.
AB  - Chordomas and low-grade chondrosarcomas of the central nervous system share many
      histological features, generating, at times, considerable diagnostic difficulty
      and, not infrequently, requiring immunohistochemical analysis for appropriate
      classification. While both chordomas and chondrosarcomas stain positively for
      S100, only chordomas typically express epithelial antigens like cytokeratins and
      epithelial membrane antigen. Positive or negative staining with these latter two
      markers currently represents the only immunohistochemical technique that
      effectively distinguishes chordomas from chondrosarcomas. A marker that is
      reliably positive in chondrosarcomas and negative in chordomas has, to date, not
      been reported. D2-40 is a monoclonal antibody initially developed against M2A, a
      fetal testis-related antigen now known as podoplanin (aggrus), which has been
      found to stain a diverse collection of both benign and malignant tissues. In this
      study, we systematically investigated D2-40 immunoreactivity in a series of 22
      chordomas, 20 chondrosarcomas, and 12 enchondromas, in conjunction with
      cytokeratin and S100 immunostaining. We found that D2-40 robustly and reliably
      immunostains low-grade chondroid neoplasms (100% of enchondromas and 94% of
      grades I and II chondrosarcomas), but not chordomas. By contrast, we observed
      generally strong and diffuse cytokeratin positivity in all cases of chordoma, but
      not in cases of enchondroma or low-grade chondrosarcoma. Thus, we show that D2-40
      behaves as a chondroid marker differentiating true chondroid neoplasms from
      chordoma. We also demonstrate D2-40 immunoreactivity in two cases of chordoid
      meningioma and, in doing so, tentatively provide a means to distinguish this
      tumor from chordoma.

PMID- 17021753
TI  - Presence of binucleate neurons in the spinal cord of young and senile rats.
AB  - The presence of binucleate cells constitutes a normal feature of some animal
      tissues but is rare in the normal brain and has not been documented in the spinal
      cord. We assessed different segments of the rat spinal cord in order to determine
      the frequency and distribution of binucleate neurons in this structure as well as
      the impact of aging on this neuronal population. Young (4-5 months) and senile
      (32 months) female Sprague-Dawley rats were used. Sections from cervical,
      thoracic and lumbar segments were histochemically and immunohistochemically
      (NeuN) stained and the frequency and distribution of binucleate neurons was
      determined by manual counting. The frequency of binucleate neurons in all of the
      analysed segments was comparable between young and senile animals. Binucleate
      neurons were particularly frequent in the C5 and C6 segments. The overall
      distribution of binucleate neurons in the different laminae assessed was, Lm-III
      = 19%; Lm-VI = 17%; Lm-VII = 39%; LmVIII = 8%; Lm-IX = 11%; Lm-X = 6%, and was
      comparable between young and senile rats. We conclude that binucleate neurons
      occur as a normal feature of the rat spinal cord and that their frequency and
      distribution does not change with aging.

PMID- 17021754
TI  - Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration:
      classification and relation to clinical phenotype.
AB  - We have investigated the extent and pattern of immunostaining for ubiquitin
      protein (UBQ) in 60 patients with frontotemporal lobar degeneration (FTLD) with
      ubiquitin-positive, tau-negative inclusions (FTLD-U), 37 of whom were ascertained
      in Manchester UK and 23 in Newcastle-Upon-Tyne, UK. There were three distinct
      histological patterns according to the form and distribution of the UBQ
      pathology. Histological type 1 was present in 19 patients (32%) and characterised
      by the presence of a moderate number, or numerous, UBQ immunoreactive neurites
      and intraneuronal cytoplasmic inclusions within layer II of the frontal and
      temporal cerebral cortex, and cytoplasmic inclusions within granule cells of the
      dentate gyrus; neuronal intranuclear inclusions (NII) of a "cat's eye" or
      "lentiform" appearance were present in 17 of these patients. In histological type
      2 (16 patients, 27%), UBQ neurites were predominantly, or exclusively, present
      with few intraneuronal cytoplasmic inclusions within layer II of the cerebral
      cortex, while in histological type 3 (25 patients, 42%), UBQ intraneuronal
      cytoplasmic inclusions either within the cortical layer II or in the granule
      cells of the dentate gyrus, with few or no UBQ neurites, were seen. In neither of
      these latter two groups were NII present. The influence of histological type on
      clinical phenotype was highly significant with type 1 histology being associated
      clinically with cases of frontotemporal dementia (FTD) or progressive non-fluent
      aphasia (PNFA), type 2 histology with semantic dementia (SD), and type 3
      histology with FTD, or FTD and motor neurone disease (MND).

PMID- 17021755
TI  - Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic
      plaques and neurofibrillary tangles.
AB  - The role of intracranial atherosclerosis in Alzheimer's disease (AD) has been a
      subject of debate since the first decade of the last century. The initial
      "vascular hypothesis" of AD was rejected after a series of mid-twentieth century
      gross anatomical postmortem studies that showed an inconstant relationship
      between intracranial atherosclerosis and senile dementia. These early studies did
      not utilize statistical methods, however, and the investigators did not appear to
      consider the possibility that intracranial atherosclerosis might have a
      probabilistic, rather than an absolute, effect on AD risk. Recent studies by
      three independent groups have found a significant statistical association between
      postmortem measures of circle of Willis atherosclerosis and AD. The present study
      was undertaken to further address the validity of this association in a large
      autopsy series, including cases diagnosed neuropathologically with vascular
      dementia (VaD) and non-AD dementias. Postmortem gross anatomical grading of
      circle of Willis atherosclerosis was performed in 397 subjects classified by
      neuropathological diagnosis, including 92 non-demented elderly controls, 215 with
      AD, 30 with VaD and 60 with non-AD dementias. Circle of Willis atherosclerosis
      was more severe in subjects with AD and VaD than in control subjects, while it
      was equivalent between control subjects and subjects with non-AD dementias.
      Increasing atherosclerotic grade increased the odds ratios (OR) for the diagnoses
      of both AD and VaD and also increased the ORs for both increased neuritic plaque
      density and higher Braak neurofibrillary tangle stage. The significance of these
      associations was retained after consideration of the effects of age, gender and
      the apolipoprotein E-epsilon4 allele. The results suggest that the statistical
      association between intracranial atherosclerosis and AD is not an artifact of
      diagnostic misclassification or of unequal distribution of the apolipoprotein E
      epsilon4 allele.

PMID- 17021756
TI  - Acute but not chronic stimulation of glial cells in rat spinal cord by systemic
      injection of lipopolysaccharide is associated with hyperalgesia.
AB  - We have analyzed development of mechanical hyperalgesia after repeated systemic
      lipopolysaccharide (LPS) injections and correlated these findings with
      stimulation of astrocytes and microglia in spinal cord. Male Lewis rats received
      a single or seven intraperitoneal injections of LPS. Mechanical hyperalgesia was
      measured as rat hindpaw withdrawal thresholds (PWTs). We observed that a single
      LPS injection elicited a specific change of PWTs while stimulated spinal glial
      activation was identified by immunoreactivities of specific markers, ED1, P2X4
      receptor, endothelial monocyte activating polypeptide II (EMAP II) and glial
      fibrillary acidic protein (GFAP), respectively; multiple LPS treatments induced
      tolerance to mechanical hyperalgesia, whereas expression of ED1 and GFAP were
      further increased. In conclusion, we have demonstrated that the number of
      activated spinal glial cells was increased as an acute effect of LPS correlating
      with increased sensitivity to mechanical stimulation. However chronic exposure to
      LPS can develop a tolerance to mechanical hyperalgesia despite ongoing signs of
      CNS glial activation.

PMID- 17021757
TI  - Compartment syndrome in the hand due to extravasation of contrast material.
AB  - Extravasation of contrast material is a well-recognized complication of contrast
      enhanced imaging studies. Most extravasations result only in minimal swelling or
      erythema; however, severe skin necrosis, ulceration and compartment syndrome may
      occur with extravasation of large volumes. This article presents a patient in
      whom extravasation developed after computed tomography (CT) contrast material was
      injected intravenously in the dorsum of the hand. Compartment syndrome was
      diagnosed, and the patient underwent fasciotomy. In follow-up, the patient
      regained full use of the hand. Although the use of contrast material has
      significantly improved the diagnostic accuracy of CT, anaphylaxis and contrast
      material extravasation are important complications. Selection of non-ionic
      contrast material, careful evaluation of the intravenous administration site and
      close monitoring of the patient during contrast material injection may help
      minimize or prevent extravasation injuries.

PMID- 17021758
TI  - Posterior stability in fixed-bearing versus mobile-bearing total knee
      replacement: a radiological comparison of two implants.
AB  - INTRODUCTION: Posterior tibial translation in total knee replacement (TKR) could
      be one major factor for PE wear, delamination and loosening of the tibial
      component due to increased shear forces and component-to-bone interface stress.
      The aim of this study was to assess the posterior stability of two different
      designs of posterior cruciate ligament (PCL) substituting TKR. METHOD: In this
      non-randomised consecutive study 43 patients underwent TKR for primary
      osteoarthritis. Twenty-six patients in group FB received a deep-dished fixed
      bearing Duracon TKR (Howmedica, Rutherford, NJ, USA) and 17 patients in group MB
      a deep-dished rotating mobile-bearing Duracon TKR. In both groups the PCL was
      resected. All patients had pre- and postoperative kneeling stress radiographs and
      were clinically evaluated with the Knee Society Score. Posterior tibial
      translation was measured by tracing a line along the posterior tibial cortex in
      relationship to the posterior edge of Blumensaat's line. RESULTS: The average
      follow-up was 13 months for group FB and 11 months for group MB. Both groups
      demonstrated a statistical significant increase of the mean posterior tibial
      translation on kneeling stress X-ray of 4.1 mm (group FB) (P < 0.001) and of 6.6
      mm (group MB) (P < 0.001) compared to pre-operative. Group MB showed a
      significant higher posterior draw (P < 0.008). Clinical assessment using the Knee
      Society Score showed comparable short-term results. CONCLUSION: The deep-dished
      fixed-bearing TKR as well as the deep-dished rotating mobile-bearing TKR
      demonstrated significant posterior tibial translation on kneeling stress X-ray.
      It remains to be determined what amount of joint play is optimal for clinical
      function and to minimise shear forces and PE wear. Moreover the amount of
      posterior tibial translation was significantly higher with the mobile-bearing
      insert, which could be directly related to the asymmetric rotational mobility of
      the tibial insert. A long-term follow-up is necessary to investigate whether our
      findings correlate with the survival-rate of these specific implants.

PMID- 17021759
TI  - Fractures of the sternum: the influence of non-invasive cardiac monitoring on
      management.
AB  - Management of sternal fractures often involves a protracted hospital stay. This
      is often based on serial electrocardiography (ECG) and cardiac enzyme measurement
      (AST, CK, LDH). This retrospective study examined all cases of sternal fracture
      presenting to our institution between October 1998 and February 2003. Seventy-two
      cases were identified, 52 of which had isolated sternal fractures. Of these, 11
      (21%) patients had an elevation in all cardiac enzymes. Twenty-three (44%) had an
      increase in some but not all. A single patient with ECG changes had no elevation
      in cardiac enzymes. Those patients with elevated cardiac enzymes had a
      significantly longer stay of 5.5 days compared with 3.7 days (P < 0.05). No
      adverse outcome was recorded in either group. We conclude that ECG and estimation
      of cardiac enzymes in these patients are of limited benefit and, when abnormal,
      appear to be associated with a significantly protracted and probably unnecessary
      hospitalisation.

PMID- 17021760
TI  - Free functional gracilis muscle transfer for reconstruction of massive ectopic
      calcification following a lower extremity fracture: a case report and overview of
      the literature.
AB  - We present a patient with massive posttraumatic ectopic calcification in the
      lower extremity. The patient complained of an increasing tender soft tissue mass
      with signs of acute inflammation and foot dorsiflexion weakness following a
      tibial fracture for 34 years. A large radiopaque mass was resected and
      reconstructed using a free functional gracilis muscle transfer, resulting in
      recovery of stable soft tissue and foot dorsiflexion. The resected material
      showed highly fibrosed soft tissue with extensive dystrophic calcifications.
      There were no sign of recurrence at 18-month follow-up.

PMID- 17021761
TI  - The importance of disease associations and concomitant therapy for the long-term
      management of psoriasis patients.
AB  - It is well established that several inflammatory-type conditions, such as
      arthritis, diabetes, cardiovascular disease, and irritable bowel disease exist
      comorbidly and at an increased incidence in patients with psoriasis. Psoriasis
      and other associated diseases are thought to share common inflammatory pathways.
      Conditions such as these, with similar pathogenic mechanisms involving cytokine
      dysregulation, are referred to as immune-mediated inflammatory diseases (IMIDs).
      Considerable evidence for the genetic basis of comorbidities in psoriasis exists.
      The WHO has reported that the occurrence of chronic diseases, including IMIDs,
      are a rising global burden. In addition, conditions linked with psoriasis have
      been associated with increasing rates of considerable morbidity and mortality.
      The presence of comorbid conditions in psoriasis patients has important
      implications for clinical management. QoL, direct health care expenditures and
      pharmacokinetics of concomitant therapies are impacted by the presence of
      comorbid conditions. For example, methotrexate is contraindicated in hepatic
      impairment, while patients on cyclosporin should be monitored for kidney
      function. In addition, some agents, such as beta blockers, lithium, synthetic
      antimalarial drugs, NSAIDs and tetracycline antibiotics, have been implicated in
      the initiation or exacerbation of psoriasis. Consequently, collaboration between
      physicians in different specialties is essential to ensuring that psoriasis
      treatment benefits the patient without exacerbating associated conditions.

PMID- 17021762
TI  - Abnormal expression of interleukin-23 in mycosis fungoides/Sezary syndrome
      lesions.
AB  - Progression of mycosis fungoides (MF) to Sezary syndrome (SS) is accompanied by a
      shift from a T(H)1 to a T(H)2 cytokine profile. Interleukin (IL)-23 is a novel
      cytokine that shares a common p40 subunit with the T(H)1 inducer, IL-12. IL-23
      induces a third profile, T(H)IL-17, that is dominant in inflammation and
      autoimmunity. Although IL-23 induces an eczematous-like skin reaction in mice,
      and is expressed in T(H)1-mediated skin disorders such as psoriasis, it has not
      been evaluated in MF/SS. To study the role of IL-23 in MF/SS development, 40
      MF/SS lesions of all stages were immunohistochemically analyzed with a novel anti
      human IL-23 antibody raised against full-length human IL-23. IL-23 was detected
      with the catalyzed signal amplification system. The intensity and frequency of IL
      23 staining were semi-quantitatively graded in both the dermal infiltrate and the
      epidermis. Increased expression of IL-23 was observed throughout the epidermal
      keratinocytes and in dermal lymphocytes compared to normal skin. IL-23 intensity
      did not differ significantly among the stages of MF/SS; however, in stage IVB
      patients, we observed lower frequency of IL-23 expression in dermal lymphocytes
      than in other stage patients [P = 0.13, analysis of variance (ANOVA)].
      Interestingly, clusters of atypical lymphocytes, especially the epidermotropic
      tumor cells, demonstrated weak or absent IL-23 staining in 18 of 40 (45%)
      lesions. This finding was present in 4 of 5 (80%) of the stage IVB lesions and 7
      of 11 (64%) of the lesions from Sezary patients. These findings indicate that
      abnormal IL-23 expression may play a role in the pathogenesis and progression of
      MF/SS.

PMID- 17021763
TI  - Increased prevalence of the metabolic syndrome in patients with moderate to
      severe psoriasis.
AB  - The role of chronic inflammation causing metabolic and vascular disorders is
      increasingly recognized. It is hypothesized that proinflammatory cytokines
      contribute to atherogenesis, peripheral insulin resistance, and the development
      of hypertension and type II diabetes. Psoriasis as a chronic inflammatory skin
      disorder is characterized by a variety of immunologic and inflammatory changes
      and may similarly predispose for those disorders. The objective of this study was
      to elucidate the association of psoriasis with chronic vascular and metabolic
      disorders. We investigated a total of 581 adult patients hospitalised for plaque
      type psoriasis as compared to 1,044 hospital-based controls. A distinct pattern
      of chronic disorders was found to be significantly associated with psoriasis,
      including diabetes mellitus type II [odds ratio (OR)=2.48], arterial hypertension
      (OR = 3.27), hyperlipidemia (OR = 2.09), and coronary heart disease (OR = 1.95).
      The combined presence of these conditions together with obesity, known as the
      metabolic syndrome, was clearly more prevalent in psoriasis patients (OR = 5.29).
      In addition, psoriasis patients were significantly more likely to be smokers (OR
      = 2.96) and to have a regular or heavy consumption of alcohol (OR = 3.33 and
      3.61, respectively). In conclusion, psoriasis patients appear to be at higher
      risk for diabetes mellitus and cardiovascular disease. This could likely be due
      to the effects of chronic inflammatory changes, in particular the secretion of
      proinflammatory cytokines. The risk of late term cardiovascular complications
      might support the use of systemic treatment in psoriasis.

PMID- 17021764
TI  - N-linked neutral oligosaccharides in the stratum corneum of normal and ichthyotic
      skin.
AB  - N-Glycan oligosaccharides are thought to play multiple, important roles in a
      variety of biological events. However, N-glycan profiles in the stratum corneum
      of human skin have not yet been studied in detail. To clarify the N-glycan
      profiles in the stratum corneum of normal and ichthyotic epidermis, N-glycan
      profiles were studied by high-performance liquid chromatography using normal
      human epidermal samples and scales from hyperkeratotic skin of ichthyosis
      patients. Chromatograms of patient scale samples showed unique alterations in
      three peaks eluted at 15.8, 18.8 and 26.9 min. The N-glycan profiles were
      significantly altered in ichthyotic hyperkeratotic skin compared with normal non
      hyperkeratotic controls. These findings indicate the reduction of N
      acetylglucosaminyltransferase II and fucosyltransferase 8 activities. Alteration
      of N-glycan structures in hyperkeratotic skin suggests the biological role of N
      glycans in keratinization.

PMID- 17021765
TI  - Identification of two novel DSRAD mutations in two Chinese families with
      dyschromatosis symmetrica hereditaria.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a hereditary skin disease
      characterized by the presence of hyperpigmented and hypopigmented macules on face
      and dorsal aspects of the extremities that appear in infancy or early childhood.
      Genetic studies have identified mutations in the double-stranded RNA-specific
      adenosine deaminase (DSRAD) gene, encoding double-stranded RNA-specific adenosine
      deaminase, to be responsible for this disorder. Here, we report two novel
      mutations c.2116 G > A (E706K) and c.2848 C > T (Q950X) in the DSRAD gene
      identified in two Chinese pedigrees with DSH. This study should be useful for
      genetic counseling and prenatal diagnosis for affected families and in expanding
      the database on DSRAD gene mutations in DSH.

PMID- 17021766
TI  - In vivo levels of IL-4, IL-10, TGF-beta1 and IFN-gamma mRNA of the peripheral
      blood mononuclear cells in patients with alopecia areata in comparison to those
      in patients with atopic dermatitis.
AB  - Alopecia areata (AA) has been considered to be supported by an aberrant
      expression of IFN-gamma as a result of antigen dependent immune response. On the
      other hand, AA sometimes concurs with atopic diseases, although the mechanism of
      the concurrence is not clear. This study was designed to elucidate the immune
      status of AA and the similarity between AA and atopic dermatitis (AD) by analysis
      of in vivo levels of mRNA of Th1, Th2, and suppressive cytokines of peripheral
      blood mononuclear cells (PBMC). Using semiquantitative RT-PCR, the levels of
      cytokine mRNA were measured in freshly isolated PBMC of 47 patients with AA, 15
      patients with AD, and 12 healthy controls (HC). The levels of IL-4, IFN-gamma,
      and TGF-beta1 mRNA were lower in patients with AA than those in HC. The levels of
      IL-10 mRNA in AA were comparable with those in HC. Decreased levels of IFN-gamma
      and TGF-beta1 were also shown in patients with AD. These results indicated a
      similarity (decreased levels of IFN-gamma and TGF-beta1) between AD and AA based
      on the cytokine profile. In addition, decreased levels of IL-4 mRNA in AA might
      also explain the experience that the severity of atopic disease coincident with
      AA is mild in the most of cases. Next, we compared the levels of these cytokine
      mRNA among the three subgroups of AA that were categorized based on the severity
      of the symptoms: mild, severe and totalis. Although there was no significant
      difference between any combinations of the subgroups, there was a tendency to
      increase the levels of IFN-gamma mRNA and to decrease the levels of IL-4 mRNA
      according to the severity of alopecia. However, the levels of IFN-gamma mRNA in
      any subgroups were less than those of HC. These results suggest that IFN-gamma is
      therefore involved in the pathogenesis of AA, although the information from PBMC
      is limited. In conclusion, AA might be induced by an aberrant expression of IFN
      gamma in individuals whose PBMC produce low amounts of IFN-gamma and TGF-beta1.
      Further analysis is therefore required to investigate the phenotypes of the
      population in PBMC with or without reference to regulatory T cells.

PMID- 17021767
TI  - Association of HLA loci alleles and antigens in Saudi patients with vitiligo.
AB  - HLA complex is composed of several closely linked loci, each containing several
      alleles, yielding a high expression of polymorphism. Vitiligo, a commonly
      acquired dermatological disorder, has been associated with different HLA antigens
      in different ethnic groups. In this study, HLA classes I (HLA-A, B, and C) and II
      (HLA-DR, DQ) antigens/alleles were analyzed in a group of 80 Saudi subjects
      consisting of vitiligo patients (40) and matched controls (40). The frequency of
      antigens of various HLA loci was tested using two-stage microcytotoxicity assays,
      while the frequency of alleles of HLA-DR was screened by polymerase chain
      reaction/sequence specific primers (PCR/SSP) method. The frequencies of HLA-B7,
      B15, Bw6, Cw6, Cw7, and DRB4*010101 were found to be significantly higher in
      vitiligo patients compared to controls [P = 0.029, 0.015, 0.033, 0.009, 0.043,
      and 0.015, respectively, with relative risk (RR) > or = 3, etiologic fraction
      (EF) > or = 0.4]. On the other hand, HLA-A9, B5, DQ1, and DRB3*010101 were
      significantly decreased in vitiligo patients compared to healthy Saudis [P =
      0.008, 0.004, 0.028, and 0.04, respectively, with RR < 1 and preventive fraction
      (PF) < 0.5]. Among the patients, the highest allele frequency was noted for
      DRB4*010101(70%), while in controls it was for DRB3*010101 (72.5%). These results
      for antigens and allele frequency of various HLA Loci in vitiligo patients and
      control subjects suggested that HLA-B7, Bw6, Cw6, Cw7, and DRB4*010101 could be
      susceptible to vitiligo, while HLA-A9, B5, DQ1, and DRB3*010101 might be
      negatively associated with the development of vitiligo in Saudis.

PMID- 17021768
TI  - The incidence of arthropathy adverse events in efalizumab-treated patients is low
      and similar to placebo and does not increase with long-term treatment: pooled
      analysis of data from Phase III clinical trials of efalizumab.
AB  - A large-scale, pooled analysis of safety data from five Phase III clinical trials
      (including open-label extensions of two of these studies) and two Phase III open
      label clinical trials of efalizumab was conducted to explore whether arthropathy
      adverse events (AEs) were associated with efalizumab treatment in patients with
      moderate-to-severe chronic plaque psoriasis. Data from patients who received
      subcutaneous injections of efalizumab or placebo were stratified for analysis
      into phases according to the nature and duration of treatment. These included:
      the 'first treatment' phase (0-12-week data from patients who received either
      efalizumab, 1 mg/kg once weekly, or placebo in the five placebo-controlled
      studies); the 'extended treatment' phase (13-24-week data from seven trials for
      all efalizumab-treated patients); and the 'long-term treatment' phase (data from
      efalizumab-treated patients who received treatment for up to 36 months in two
      long-term trials). Descriptive statistics were performed and the incidence of
      arthropathy AEs per patient-year was calculated using 95% confidence intervals
      (CIs). During the first treatment phase, a similar proportion of patients had an
      arthropathy AE in the efalizumab group (3.3%; 58/1740 patients) compared with the
      placebo group (3.5%; 34/979 patients); the incidence of arthropathy AEs per
      patient-year was 0.15 in the efalizumab group (95% CI 0.11-0.19) and 0.16 in the
      placebo group (95% CI 0.11-0.22). Analysis of first treatment phase data from one
      study (n = 793) showed that the incidence of psoriatic arthropathy per patient
      year was lower in efalizumab-treated patients (0.10; 95% CI 0.05-0.18) than in
      those given placebo (0.17; 95% CI 0.08-0.30). During the extended treatment
      phase, the incidence of arthropathy remained low (0.17; 95% CI 0.14-0.22). Data
      from two long-term studies showed that there was no increase in the incidence of
      arthropathy AEs over time in patients treated with efalizumab for up to 36
      months. Patients who had an arthropathy AE during treatment with efalizumab
      appeared to be more likely to have a history of arthropathy prior to treatment.
      Efalizumab does not appear to increase the risk of arthropathy AEs compared with
      placebo.

PMID- 17021769
TI  - Female sterilization by tubal ligation: a re-appraisal of factors influencing
      decision making in a tropical setting.
AB  - BACKGROUND: Female sterilization by tubal ligation is the most commonly used
      method of fertility regulation. However, in some lesser-developed countries like
      Nigeria, it has not been accepted as a popular method of contraception.
      OBJECTIVE: To assess the pattern of female sterilization and determine factors
      that may influence its acceptability. METHOD: A retrospective study of 102 cases
      of tubal ligation (TL) performed between January 1999 and December 2004. RESULT:
      Of the 102 patients/clients, 60 (58.8%) had TL at caesarean section, 28 (27.5%)
      had TL with repair of ruptured uterus and 14 (13.7%) clients had TL alone on
      request. In the reproductive age group, the rate of TL increased with age. In the
      group that had TL at caesarean section, the highest incidence of TL (65%) was
      recorded against parity 4. However, in the groups that had TL with repair of
      ruptured uterus and TL alone, the highest proportion of TL was recorded against
      parity 6, with rates of 46.3 and 57.1%, respectively. The rates of TL increased
      with the level of literacy. In the group that had TL alone, 92.9% of the clients
      were in a monogamous union. On the contrary, 89.3% of patients that had TL with
      repair of uterine rupture were in a polygamous union. There was relative
      distribution of patients/clients amongst the two religions and five ethnic
      grouping. In 55 of the 102 patients/clients, the indication for TL was completion
      of family size, though 41 of the 55 patients had TL at caesarean section.
      CONCLUSION: Demand for TL alone was low. A greater percentage of the patients had
      TL in conjunction with another surgical procedure.

PMID- 17021770
TI  - Live birth after laparotomy for concurrent heterotopic pregnancy and appendicitis
      in a 6 weeks IVF pregnancy.
AB  - BACKGROUND: A term delivery after concurrent appendectomy and salpingectomy at 6
      weeks in an appendicitis coexisting with a heterotopic pregnancy after in vitro
      fertilization (IVF) treatment is reported. METHODS: Case report. RESULTS: The
      patient presented with severe low abdominal pain at 6 weeks of pregnancy after
      IVF and had explorative laparotomy for appendicitis, during which she had
      appendectomy and salpingectomy for an undiagnosed concurrent heterotopic
      pregnancy. The patient delivered a 3,960 g healthy infant at 38 weeks.
      CONCLUSION: In patients with severe abdominal pain after IVF, appendicitis and
      heterotopic pregnancy should be included in the differential diagnosis. A dual
      pathology is possible and when treated appropriately it can result in survival of
      the precious intrauterine pregnancy. This is the second and earliest ever
      reported case of that resulted in live birth. It shows that explorative surgery
      must be performed timely in acute abdomen in pregnancy.

PMID- 17021771
TI  - Telemetric monitoring of tracheal pressure after tracheal occlusion for treatment
      of severe congenital diaphragmatic hernia.
AB  - INTRODUCTION: Prenatal tracheal occlusion using endoscopic techniques obstructs
      the normal egress of lung fluid during pulmonary development and stimulates lung
      growth in cases of congenital diaphragmatic hernia (CDH). Although FETO might be
      an effective strategy for treatment of CDH, the mechanism especially due to the
      supposed increasing transpulmonary pressure is unknown. OBJECTIVE: The purpose of
      this study was to monitor the pressure below the attached balloon in the fetal
      lamb telemetrically. METHODS: Four time-dated pregnant Merino ewes underwent
      fetal and maternal surgery. A special prepared silicone catheter was placed below
      the epiglottis by laryngoscopy on day 110 or 140 of gestation. The tracheal
      pressure below the fixed catheter could be monitored telemetrically using the
      Data Sciences TA11-PA-C40 pressure device. Hundred and twenty measurement points
      were recorded over a period of 2 min. RESULTS: A maximum of lung pressure rate
      was found immediately after implantation (23.7 +/- 4.6 mm Hg). During the first
      hour, the pressure decreased to an average value of 16.9 mmHg. About 70 h after
      the block, this value decreased to a minimum level of 8.3 +/- 0.4 mmHg.
      CONCLUSION: Decreasing pressure variation might indicate that lung growth has
      stopped and that the ideal point of time to remove the balloon is achieved.
      Increasing pressure has to be related to the morphometric analysis of the lung's
      structural development and maturation, comparing the efficacy of FETO in
      preventing or reversing pulmonary hypoplasia. Further investigation of continuous
      telemetric monitoring of tracheal pressure in the fetal lamb is required.

PMID- 17021772
TI  - Chronic abdominal pregnancy following rupture from a bicornuate uterus.
AB  - The authors report a rare occurrence of a chronic abdominal pregnancy secondary
      to a ruptured bicornuate uterus. It is unusual in that rupture of the uterine
      horn probably occurred 2 weeks prior to diagnosis. Management was laparotomy to
      remove the fetus with resection and repair of the uterus. Uterine anomalies,
      their imaging and diagnosis, as well as the patient's subsequent reproductive
      prognosis are discussed.

PMID- 17021773
TI  - Epidural anaesthesia for labour: does it influence the mode of delivery?
AB  - BACKGROUND: Epidural anaesthesia (EDA) is an effective method to lower labour
      pain. EDA might have an impact on instrumental delivery rates and on caesarean
      section rates. The present study compares the mode of delivery in women who were
      either receiving EDA or not. The indication for EDA was pain relief only in order
      to switch off a selection bias. METHODS: During a 1-year duration, we included a
      total of 1,452 cases. Exclusion criteria were factors that could influence the
      mode of delivery, independent from EDA, as well as obstetrical indications for
      administering EDA. 530 women remained in the analysis. The primary outcome
      variable was the mode of delivery. RESULTS: We detected in both nullipara and
      multipara a statistically significant accumulatin in patients with EDA and
      caesarean section combined. Most importantly, the majority of the women without
      EDA (57% of nullipara and 60% of multipara) delivered within the median timeframe
      from admission until administration of EDA. CONCLUSIONS: It seems to be obvious
      to conclude that EDA as performed in our study results in a higher rate of
      caesarean sections. It is important though to take into consideration that
      between the period from admission to the delivery ward and administration of EDA
      most of the parturients without EDA had already delivered. Our results make
      evident, that the administration of EDA exclusively used for reducing labour pain
      is a result of a complex collaboration of temporal conditions of labour as well
      as psychological conditions and also of the mother's wish.

PMID- 17021774
TI  - Interstitial cystitis.
AB  - Interstitial cystitis is an enigmatic and frustrating condition to manage as a
      physician and to cope with as a patient. Traditionally, it has been defined as a
      chronic sterile inflammatory disease of the bladder of unknown aetiology.
      However, the International Continence Society prefers the term painful bladder
      syndrome and it has been decided to follow this terminology and refer to the
      disease as painful bladder syndrome/interstitial cystitis (PBS/IC). The condition
      is characterized by bladder pain, urinary frequency, urgency and nocturia. The
      quality of life of patients with PBS/IC is significantly degraded. Its aetiology
      is unknown, but might involve microbiologic, immunologic, mucosal, neurogenic and
      other yet unidentified agents. History, physical examination, urine analysis and
      culture as well as cystoscopy and hydrodistension are useful diagnostic tools but
      the final diagnosis tends to be a diagnosis of exclusion. This article will
      review the major theories of aetiology for PBS/IC and discuss diagnosis as well
      as the current treatment options with relevance to the proposed aetiologies.

PMID- 17021775
TI  - Menopausal symptoms and associated risk factors among postmenopausal women
      screened for the metabolic syndrome.
AB  - BACKGROUND: Although the frequency of menopausal symptoms may vary according to
      the studied population, in general severe intensity has been related to lower
      quality of life. OBJECTIVE: To assess the frequency of menopausal symptoms and
      involved risk factors in an Ecuadorian postmenopausal population. METHODS:
      Postmenopausal women that participated in a metabolic syndrome screening program
      were interviewed with the Menopause-specific quality of life questionnaire
      (MENQOL) in order to determine the most frequently presenting menopausal symptoms
      and correlate these symptoms with socio-demographic data and the main results of
      the screening program. RESULTS: Three hundred and twenty-five postmenopausal
      women (n = 325) were surveyed with the MENQOL. Mean age of participants was 55.9
      +/- 8.1 years (median: 54 years). The most frequently presenting symptoms were:
      hot flushes (53.3%), sweating (49.2%), poor memory (80.6%), feeling depressed
      (67.4%), aching in muscles and joints (84%), drying of their skin (85.5%),
      avoiding intimacy (76.2%) and change in their sexual desire (76.5%). Multivariate
      analysis determined that abdominal obesity was a significant risk factor for
      presenting hot flushes, depression and muscle and joint pain. High triglyceride
      levels were associated to higher rates of sweating and depression. While women
      with basal hyperglycemia were associated to dry skin and changes in sexual desire
      in a higher proportion, those who were older and with more years of menopause
      onset were related less frequently to vasomotor symptoms. Older age was also
      significantly associated in a higher rate to dry skin. CONCLUSION: In this
      postmenopausal Ecuadorian population, the frequency of menopausal symptoms, as
      assessed with the MENQOL, was found to be relatively similar to other Latin and
      non-Latin American populations and associated to age, hormonal status and related
      metabolic conditions.

PMID- 17021776
TI  - Normative data for the "Sniffin' Sticks" including tests of odor identification,
      odor discrimination, and olfactory thresholds: an upgrade based on a group of
      more than 3,000 subjects.
AB  - "Sniffin' Sticks" is a test of nasal chemosensory function that is based on pen
      like odor dispensing devices, introduced some 10 years ago by Kobal and co
      workers. It consists of tests for odor threshold, discrimination, and
      identification. Previous work established its test-retest reliability and
      validity. Results of the test are presented as "TDI score", the sum of results
      obtained for threshold, discrimination, and identification measures. While
      normative data have been established they are based on a relatively small number
      of subjects, especially with regard to subjects older than 55 years where data
      from only 30 healthy subjects have been used. The present study aimed to remedy
      this situation. Now data are available from 3,282 subjects as compared to data
      from 738 subjects published previously. Disregarding sex-related differences, the
      TDI score at the tenth percentile was 24.9 in subjects younger than 15 years,
      30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6
      for subjects older than 55 years. Because the tenth percentile has been defined
      to separate hyposmia from normosmia, these data can be used as a guide to
      estimate individual olfactory ability in relation to subject's age. Absolute
      hyposmia was defined as the tenth percentile score of 16-35 year old subjects.
      Other than previous reports the present norms are also sex-differentiated with
      women outperforming men in the three olfactory tests. Further, the present data
      suggest specific changes of individual olfactory functions in relation to age,
      with odor thresholds declining most dramatically compared to odor discrimination
      and odor identification.

PMID- 17021777
TI  - Esophagus atresia after cervical spine surgery: case report and literature
      review.
AB  - We report on a case of esophageal atresia following cervical spine surgery. A
      swallowing examination was performed using fibre-optic endoscopy and
      videofluoroscopy. There was scar tissue fixation of the larynx and esophagus to
      the cervical spine. Operative mobilization of the larynx and esophagus and
      formation of a sliding layer using a platysma-fascia flap was done. The PEG and
      tracheal cannula were removed; oral nutrition was initiated after 3 months.
      Swallowing disorders following operations on the upper cervical spine should be
      investigated. Careful preparation that preserves the layers should be carried
      out. Fixation of tissues as a result of scarring should be treated with a sliding
      layer.

PMID- 17021778
TI  - Tuberculous otitis media developing as a complication of tympanostomy tube
      insertion.
AB  - Primary tuberculous otitis media of which infection focus cannot be found
      elsewhere in the body is a rare disease. Route of the infection has been
      hypothesized as Eustachian tube or external auditory canal with tympanic membrane
      perforation but it is hard to ascertain in the patient. We present a case of an 8
      year-old child who suffered chronic otorrhea after tympanostomy tube insertion.
      The radiological and histopathological findings revealed tuberculous otitis
      media, which occurred as a complication of tympanostomy tube insertion.

PMID- 17021779
TI  - The relationship between nasopharyngeal carcinoma tumor volume and TNM T
      classification: a quantitative analysis.
AB  - Recent findings show that tumor volume is a significant prognostic factor for the
      treatment of nasopharyngeal carcinoma (NPC). The inclusion of tumor volume as an
      additional prognostic factor in the UICC TNM classification system was suggested;
      however, how tumor volume could possibly be incorporated is still unexplored. In
      this paper, we report a quantitative analysis on the relationship between NPC
      tumor volume and T-classification, using the data from 206 NPC patients. By T
      classification and semi-automatic tumor volume measurement, the difference in
      tumor volumes among the various TNM T-classification groups was examined. In
      addition, a statistics-based analysis scheme, which used the T-classification as
      the "gold standard", was proposed to classify NPC tumors into volume-based groups
      to explore the possible links. The results show that NPC tumor volume has
      positive correlation with advancing T-classification groups and significant
      difference existed in the distribution of T-classification among various volume
      based groups (P < 0.001). By the proposed statistical scheme, tumor volume could
      be included as an additional prognostic factor in the TNM framework, following
      validation studies.

PMID- 17021780
TI  - Tonsillotomy or tonsillectomy?--a prospective study comparing histological and
      immunological findings in recurrent tonsillitis and tonsillar hyperplasia.
AB  - We evaluated the differences in histological and immunological findings in
      children with recurrent tonsillitis and tonsillar hyperplasia and assessed the
      risk for relapsing tonsillar hyperplasia or recurrent tonsillitis after
      tonsillotomy in a prospective clinical study. Sixty-four children with recurrent
      tonsillitis underwent traditional (total) blunt dissection tonsillectomy between
      October 2003 and July 2004. Partial tonsillectomy (tonsillotomy) using CO(2)
      laser technique was performed on 49 children with tonsillar hyperplasia and no
      history of recurrent tonsillitis between August 2003 and March 2005. The present
      study compares preoperative serum anti-streptolysin-O antibody and immunoglobulin
      levels (IgG, IgA and IgM), C-reactive protein levels (CRP) and blood leukocyte
      counts of the two study groups. Additionally the tonsillar tissue removed by
      tonsillotomy or tonsillectomy was histologically examined in order to determine
      the grade of hyperplasia, chronic inflammation and fibrosis. Furthermore, the
      grade of fresh inflammation within the tonsillar crypts of the specimens was
      analysed. The parents of 40 patients treated by laser tonsillotomy were surveyed
      in average 16 months. There was no statistically significant difference in
      preoperative serum anti-streptolysin-O antibody and immunoglobulin levels, C
      reactive protein levels and blood leukocyte counts between the two study groups.
      All specimens showed the histological picture of hyperplasia. There was no
      statistically significant difference in the grades of hyperplasia between the two
      study groups. Signs of fresh but mild inflammation within the tonsillar crypts
      could be found in over 70% of both study groups. Fibrosis only occurred in
      children with recurrent tonsillitis (9%). In all specimens signs of chronic
      inflammation could be detected. The histological examinations of specimens from
      children with repeated throat infections more frequently showed a moderate
      chronic inflammation of the tonsillar tissue. Two of forty patients treated by
      tonsillotomy required a subsequent tonsillectomy due to a recurrence of tonsillar
      hyperplasia but no recurrent tonsillitis occurred. Tonsillotomy with CO(2)-laser
      technique is an effective surgical procedure with a long-lasting effect in
      patients with tonsillar hyperplasia. The benefits over conventional tonsillectomy
      are a lower risk for postoperative haemorrhage, reduced postoperative morbidity
      and accelerated recovery. Even in children with no history of recurrent
      tonsillitis signs of chronic inflammation histologically can be found in
      specimens after tonsillotomy. The occurrence of recurrent tonsillitis after
      tonsillotomy is rare, however. A low incidence of relapsing tonsillar hyperplasia
      after tonsillotomy should be expected. Preoperative laboratory investigations
      show few differences in patients with tonsillar hyperplasia and recurrent
      tonsillitis. Components of the antimicrobial defense system are also produced by
      chronically infected tonsils. Therefore tonsillotomy with CO(2)-laser could also
      be an option in some patients with mild symptoms of recurrent tonsillitis.

PMID- 17021781
TI  - Oral tongue carcinoma and its treatment in Finland.
AB  - Management of oral tongue squamous cell cancer (OTSCC) remains a challenge. This
      nationwide study reports the used treatment approach and the outcome of OTSCC in
      Finland. Retrospective study of OTSCC patients in 1995-1999 with a 5-year follow
      up. The corresponding data from 1980 to 1989 is also included. About 235 patients
      (125 M, 110 F; mean age 61.6 years; range 24-90 years) were included, 77% had SCC
      of lateral border of the tongue and 25% were N+. Treatment with curative intent
      was given to 224 (95%) patients. Surgery of the primary tumour was performed in
      218 (97%) patients and with a reconstruction in 69 (31%) patients. A neck
      dissection was performed ipsilaterally in 114 (51%) and bilaterally in 9 (4%)
      cases. Irradiation was given to 131 (58%) patients. The rate for locoregional
      recurrence was 28%. The 3- and 5-year overall survival (OS) rates were 66 and
      47%, respectively. The corresponding disease specific survival (DSS) rates were
      74 and 64%, respectively. The mean DSS for patients younger than 40 years and
      older than 40 years was 111 and 88 months, respectively (P < 0.02). The 3- and 5
      year DSS rates were: Stage I, 88 and 74%; Stage II, 74 and 62%; Stage III, 79 and
      71% and Stage IV, 36 and 33%, respectively. In the present study the surgical
      treatment approach seems effective in controlling early stage OTSCC but the
      modest survival, in spite of combination of radiotherapy and surgery, points out
      the need to consider new strategies in the management of advanced stage disease.

PMID- 17021782
TI  - Pharyngocutaneous fistula following total laryngectomy: a single institution's 10
      year experience.
AB  - The etiology of postoperative pharyngocutaneous fistula (PCF) formation following
      major head and neck surgery is multifactorial and the incidence varies greatly.
      We reviewed retrospectively the records of 108 consecutive patients who underwent
      a total laryngectomy during the period from December 1992 to December 2002 at the
      Helsinki University Central Hospital, Helsinki, Finland. PCF occurred
      postoperatively in 19 (18%) patients. Two additional patients (2%) developed a
      PCF later than 30 days after laryngectomy. Nineteen percent of these patients
      with fistula formation had received previous radiation therapy and laryngectomy
      was performed for local recurrence. Eighteen (86%) of the all fistulae closed
      spontaneously and surgical closure of the fistula was performed in three (14%)
      cases. We conclude that the PCFs in our patient population occurred both in
      radiated and nonirradiated patients. Although most fistulae close spontaneously
      without surgical intervention this complication leads to prolonged
      hospitalization and increased patient morbidity.

PMID- 17021783
TI  - Sinonasal involvement as a rare extraintestinal manifestation of Crohn's disease.
AB  - Crohn's disease is a chronic idiopathic slowly developing transmural inflammation
      of the digestive system. It usually involves the small intestine and/or the area
      around the anus but can also affect the entire gastrointestinal tract anywhere
      from the mouth to the anus. Extra intestinal manifestations occur frequently and
      multiple organ systems may be affected: the skin, joints, spine, eyes, liver and
      bile ducts. In contrast, nasal manifestations are extremely rare and only a few
      cases have been reported up to date in the worldwide literature. The authors
      report two cases with nasal manifestations concomitant to intestinal Crohn's
      disease and go over the relevant literature on such an association.

PMID- 17021784
TI  - The use of trichloroacetic acid in the treatment of acute external otitis.
AB  - The purpose of this study was to evaluate the effectiveness of 5% trichloroacetic
      acid (TCA) in the treatment of acute external otitis (AEO) in comparison with a
      standard clinical treatment. All patients who consecutively presented in our
      emergencies with AEO during the summer months of the previous year were included
      in the study. They were randomly divided into two groups: the study group
      included 117 patients treated with TCA and the control group included 98 patients
      treated with ear drops containing antibiotic and corticosteroid. Occasionally, an
      antibiotic was administered orally for 7 days, in severe cases of AEO. All
      patients were evaluated on days 1, 3, 5, 7 and 10, whereas another review
      appointment was given 20 days later. Outcome measures included evaluation of
      efficacy using a six-step infection score and tolerability by visual analogue
      scale. Additionally, adverse reactions, complications and recurrencies were
      recorded. Treatment was successful for all patients of the study group, whereas 8
      failures were found in the control group. The infection score improved faster in
      the study group than in the control group, resulting in an earlier clinical cure
      (mean 4.1 and 8.6 days, respectively). Tolerability was significantly better in
      the study group, on all points of evaluation. Complications and adverse reactions
      were minimal on both groups. Our results show that TCA is a very effective and
      nontoxic agent for the treatment of AEO. Rapid pain relief and prevention of
      recurrencies are its main advantages.

PMID- 17021785
TI  - Safety concerns related to magnetic field exposure.
AB  - The recent development of superconducting magnets has resulted in a huge increase
      in human exposure to very large static magnetic fields of up to several teslas
      (T). Considering the rapid advances in applications and the great increases in
      the strength of magnetic fields used, especially in magnetic resonance imaging,
      safety concerns about magnetic field exposure have become a key issue. This paper
      points out some of these safety concerns and gives an overview of the findings
      about this theme, focusing mainly on mechanisms of magnetic field interaction
      with living organisms and the consequent effects.

PMID- 17021786
TI  - Scaling skeletal muscle function to mass in patients with moderate-to-severe
      COPD.
AB  - Skeletal muscle performance and muscle mass are commonly reduced in patients with
      advanced chronic obstructive pulmonary disease (COPD). It is currently unclear,
      however, whether negative changes in muscle structure and function are
      proportionately related to each other in these patients. In a cross-sectional
      study, 39 patients (post-bronchodilator FEV1=49.7+/-15.5% pred) and 17 controls
      were submitted to knee isokinetic dynamometry [peak torque (PT), isometric
      strength (IS), and total work (TW)] and dual energy X-ray absorptiometry for the
      evaluation of leg muscle mass (LMM). Muscle function (F) was normalised for LMM
      by using ratio standards (F.LMM-1), power function ratios (F.LMM-b, where b is
      usually not equal 1), and analysis of covariance (ANCOVA). Patients with COPD
      presented with reduced PT, IS, TW, and LMM as compared to controls: there were
      significant linear correlations among these variables in both groups (P<0.05).
      Ratio standards of PT.LMM-1 and TW.LMM-1 were, on average, 14% lower in patients
      than controls (P<0.01). The coefficients for allometric correction of IS and TW
      were significantly higher in patients as compared to controls (0.975 vs. 0.603
      and 1.471 vs. 0.824, respectively, P<0.05), i.e. more LMM was needed to generate
      a given functional output in patients than normal subjects. In addition, adjusted
      means of muscle function variables by ANCOVA were 11-18% lower for patients than
      controls with LMM as the covariate (P<0.05). We conclude that factors other than
      simple atrophy (i.e. mass-independent mechanisms) might play a role in explaining
      the COPD-related skeletal muscle dysfunction.

PMID- 17021787
TI  - Influence of climbing style on physiological responses during indoor rock
      climbing on routes with the same difficulty.
AB  - The objectives of this study were to (1) continuously assess oxygen uptake and
      heart rate; (2) quantify the extent to which maximal whole-body cardiorespiratory
      capacity is utilized during climbing on four routes with the same difficulty but
      different steepness and/or displacement. Fifteen expert climbers underwent a
      maximal graded exercise test (MT), on a treadmill, in order to assess their
      maximal physiological capacity. After MT, four sport routes, equal in difficulty
      rating but different in steepness and/or displacement, were climbed. Oxygen
      uptake and heart rate were continuously measured. Respiratory exchange ratio
      (RER) was calculated. Blood lactate concentration and rating of perceived
      exertion (RPE) were taken before and directly after climbing. Data were expressed
      as peak values (HRpeak, VO2peak and RERpeak) and as averages over the entire
      climb (HRavg, VO2avg and RERavg). During climbing, higher HRpeak and HRavg were
      found in routes with a vertical upward displacement in comparison to traversing
      routes with a horizontal displacement. The average absolute and relative oxygen
      uptake was significantly lower in the traversing route in comparison with the
      three other routes. The traverse is done at a lower percent of the running
      maximum. Comparing four routes with the same difficulty but different steepness
      and/or displacement shows that (1) routes with an upward displacement causes the
      highest peak and average heart rate; (2) routes with a vertical displacement on
      overhanging wall is physiologically the most demanding; (3) the traverse is
      physiologically the less demanding.

PMID- 17021789
TI  - Implantation of parathyroid carcinoma along fine needle aspiration track.
AB  - INTRODUCTION: Fine needle aspiration cytology is not a commonly employed
      diagnostic modality in the diagnosis of parathyroid tumors. CASE REPORT: A 28
      year old lady being followed-up for 5 years after en bloc resection of a
      parathyroid carcinoma presented with a nodule in the lower neck, away from the
      parathyroidectomy scar. The 1 cm isolated nodule was located in the muscular and
      subcutaneous plane and corresponded to the needle track of FNA performed on a
      neck nodule before the parathyroidectomy. On evaluation, she had mild
      hypercalcemia and high normal serum parathyroid hormone levels. FNAC and
      histology including immunohistochemistry for Chromogranin A after local excision
      of the nodule confirmed the nodule to be a recurrent parathyroid carcinoma along
      the needle track. DISCUSSION: To the best of the authors' knowledge, this is only
      the second case of needle track implantation after FNA in parathyroid carcinoma
      reported to date. This case highlights the risk of engraftment of parathyroid
      tissue after FNA and cautions against the use of FNA as a preoperative diagnostic
      modality for the evaluation of parathyroid lesions.

PMID- 17021788
TI  - Therapeutic strategies for the management of delayed gastric emptying after
      pancreatic resection.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is one of the most troublesome
      postoperative complications following pancreatic resection. Not only does it
      contribute considerably to prolonged hospitalization, but it is also associated
      with increased postoperative morbidity and mortality. METHODS: We performed an
      electronic and manual search of the international literature for studies dealing
      with the treatment of DGE following pancreatic resection using the Medline
      database. The search items used were "delayed gastric emptying,"
      "pancreaticoduodenectomy," "Whipple procedure," "pylorus-preserving
      pancreaticoduodenectomy," and "complications following pancreatic resection" in
      various combinations. RESULTS: A number of studies were identified regarding
      possible therapeutic alternatives for the treatment of DGE. From the class of
      prokinetic regimens, most studies seem to support the use of erythromycin.
      However, its use has not gained wide acceptance. Regarding the operative
      technique, both standard Whipple and pylorus-preserving pancreatic resection
      carry similar rates of DGE. Billroth II type-like gastrointestinal reconstruction
      is the most widely accepted method and is associated with lower rates of DGE.
      Reoperations for managing severe DGE were very rarely reported. CONCLUSIONS: The
      incidence of DGE in high-volume centers specialized in pancreatic surgery is well
      below 20%, thus following the improved rates that have been reported in the last
      decade regarding mortality and length of hospital stay after pancreatic surgery.
      DGE mandates a uniform definition and method of evaluation to achieve homogeneity
      among studies. Standardization of the operative technique, as well as
      "centralizing" pancreatic resections in high-volume centers, should aid to
      improve the occurrence of this bothersome postoperative complication.

PMID- 17021790
TI  - True smooth muscle neoplasms of the gastrointestinal tract: morphological
      spectrum and classification in a series of 85 cases from a single institute.
AB  - BACKGROUND AND AIM: True smooth-muscle neoplasms of the GI tract have been only
      rarely studied in the KIT era. Their incidence among other GI mesenchymal tumours
      and their clinicopathological spectrum have not been sufficiently analysed.
      MATERIALS AND METHODS: We reviewed all GI mesenchymal lesions at the Pathology
      Institute of the Nuremberg Clinic Centre from 1994 through 2005. RESULTS: Among
      262 lesions, there were 142 GISTs (54%) and 85 true smooth muscle neoplasms
      (32%). Smooth muscle neoplasms comprised 72 polypoid leiomyomas (78%, 5
      oesophageal and 67 colorectal), 10 intramural leiomyomas (11%, 5 oesophageal, 4
      gastric and one ileal), two intramural leiomyosarcomas in the sigmoid colon and
      ileum (2%) and one polypoid leiomyosarcoma involving the stomach, descending
      colon and the retroperitoneum concurrently. None of the leiomyomas with available
      follow-up have recurred or metastasised. CONCLUSION: Smooth muscle neoplasms are
      the second most common mesenchymal neoplasms in the GI tract after GISTs. They
      may arise either from the muscularis mucosae or proper muscle layer forming
      polypoid and intramural lesions, respectively. Polypoid leiomyomas are more
      common in the rectosigmoid, while intramural ones mainly arise in the vicinity of
      the oesophagogastric junction. Polypoid leiomyomas are sufficiently treated by
      endoscopic resection, and local surgical excision is the treatment of choice for
      intramural leiomyomas. Intramural leiomyosarcomas are rare high-grade sarcomas
      that commonly have infiltrated into the surrounding tissue or metastasised by the
      time of diagnosis.

PMID- 17021791
TI  - The advantage of near-total thyroidectomy to avoid postoperative
      hypoparathyroidism in benign multinodular goiter.
AB  - BACKGROUND: In recent years, total or near-total thyroidectomy has emerged as a
      surgical option to treat patients with multinodular goiter, especially in endemic
      iodine-deficient regions. The aim of this study was to compare the complication
      rates of total and near-total thyroidectomy in multinodular goiter and the
      incidence of thyroid cancer requiring radioactive iodine ablation and completion
      thyroidectomy between groups. STUDY DESIGN: Patients with euthyroid multinodular
      goiter without any preoperative suspicion of malignancy, history of familial
      thyroid cancer, or previous exposure to radiation were randomized (according to a
      random table) to total thyroidectomy (group 1, n = 104) and near-total
      thyroidectomy leaving less than 2 g (group 2, n = 112). RESULTS: There were no
      persistent complications. The incidence of transient hypoparathyroidism in group
      1 (26%) was significantly higher than in group 2 (9.8%) (p < 0.001). The rate of
      asymptomatic hypocalcemia in group 2 (7.4%) was lower than in group 1 (27%) (p <
      0.001). The incidence of papillary cancer was 9.6% in group 1 and 12.5% in group
      2 (p > 0.05). None of the patients underwent completion thyroidectomy before
      ablative therapy. Ten patients were found to have the histological criteria for
      radioactive iodine ablation. Of these 10 patients, four were in group 1 and six
      were in group 2 (p > 0.05). CONCLUSION: In conclusion, we recommend near-total
      thyroidectomy in multinodular goiter instead of total or subtotal thyroidectomy.
      While near-total thyroidectomy and total thyroidectomy obviate the need for
      completion thyroidectomy in incidentally found thyroid cancer, and while there is
      no difference in the rate of recurrent laryngeal nerve palsy between the two
      methods, near-total thyroidectomy causes a significantly lower rate of
      hypoparathyroidism compared to total thyroidectomy.

PMID- 17021792
TI  - Predictors of morbidity and mortality in the surgical management of hydatid cyst
      of the liver.
AB  - BACKGROUND/AIMS: Surgery for hydatid cyst of the liver is widely practiced
      worldwide; this type of management is still associated with high mortality and
      morbidity. The aim of this study is to find out possible predictors for this high
      mortality and morbidity. MATERIALS AND METHODS: The medical records of 169
      patients who underwent surgery for hydatid cyst of the liver were retrospectively
      reviewed. The mortality and the morbidity rates were assessed as well as the
      following eight potential predictors of mortality and morbidity: age of the
      patients, size of the cyst, number of cysts, other organs involved by the
      disease, the presence of preoperative complications, the type of surgery
      performed (radical or conservative), whether the disease was new or recurrent,
      and when surgery was performed in the first period (1973-1986) or in the second
      period (1987-1999). Cross-tabulation and logistic regression between mortality
      and morbidity (dependent variable) and the above-mentioned eight potential
      predictors (independent variables) were carried out. RESULTS: Of the 169
      patients, 112 were female subjects and 57 male subjects, the age range was from 5
      to 85 years (mean=39.2 years), the mortality rate was 6.5% (n=11), and the
      overall morbidity rate was 53.8% (n=91), while specific complications of liver
      hydatid cyst surgery were seen in 32% (n=54). Patients of age >40 years, with a
      cyst diameter of >10 cm, who presented with pre-operative complications, who had
      conservative surgery, and who had surgery before 1987 were having a significantly
      higher mortality and morbidity rate. CONCLUSION: Age, size of the cyst, the
      presence of pre-operative complications particularly cyst-biliary communication,
      and type of surgical procedure performed (conservative or radical) represent as
      significant predictors of mortality and morbidity of surgery for liver hydatid
      cyst.

PMID- 17021793
TI  - Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle
      fibres.
AB  - We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel
      disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined
      how this mutation, Gly159Asp, affects contractile regulation when incorporated
      into muscle fibres. Endogenous troponin in rabbit skinned psoas fibres was
      partially replaced by recombinant human cardiac troponin containing either wild
      type or Gly159Asp TnC. We measured both the force-pCa relationship of these
      fibres and the activation rate using the caged-Ca(2+) compound nitrophenyl-EGTA.
      Gly159Asp TnC had no significant effect on either the Ca(2+) sensitivity or
      cooperativity of force generation when compared to wild type. However, the
      mutation caused a highly significant (ca. 50%) decrease in the rate of
      activation. This study shows that whilst not affecting the force-pCa
      relationship, the mutation Gly159Asp causes a significant decrease in the rate of
      force production and a change in the relationship between the rate of force
      production and generated force. In vivo, this mutation may cause both a slowing
      of force generation and reduction in total systolic force. This represents a
      novel mechanism by which a cardiomyopathy-causing mutation can affect
      contractility.

PMID- 17021794
TI  - Aquaporin expression and cell volume regulation in the SV40 immortalized rat
      submandibular acinar cell line.
AB  - The amount of aquaporins present and the cellular ability to perform regulatory
      volume changes are likely to be important for fluid secretions from exocrine
      glands. In this work these phenomena were studied in an SV40 immortalized rat
      submandibular acinar cell line. The regulatory cell volume characteristics have
      not previously been determined in these cells. Cell volume regulation following
      hyposmotic exposure and aquaporin induction was examined with Coulter counter
      methodology, radioactive efflux studies, fura-2 fluorescence, and polymerase
      chain reaction and Western blot techniques. Cell volume regulation was inhibited
      by the K(+) channel antagonists quinine and BaCl(2) and the Cl(-) channel blocker
      5-nitro-2-(3-phenypropylamino)benzoic acid. A concomitant increase in cellular
      (3)H-taurine release and Ca(2+) concentration was also observed. Chelation of
      both intra- and extracellular Ca(2+) with EGTA and the Ca(2+) ionophore A23187
      did not, however, affect cell volume regulation. Aquaporin 5 (AQP5) mRNA and
      protein levels were upregulated in hyperosmotic conditions and downregulated upon
      return to isosmotic solutions, but were reduced by the mitogen-activated ERK
      activating kinase (MEK) inhibitor U0126. A 24-h MEK inhibition also diminished
      hyposmotically induced cell swelling and cell volume regulation. In conclusion,
      it was determined that regulatory volume changes in this immortalized cell line
      are due to KCl and taurine efflux. In conditions that increased AQP5 levels, the
      cells showed a faster cell swelling and a more complete volume recovery following
      hyposmotic exposure. This response could be overturned by MEK inhibition.

PMID- 17021795
TI  - Differentiation-dependent alterations in the extracellular ATP-evoked calcium
      fluxes of cultured skeletal muscle cells from mice.
AB  - Although extracellular adenosine triphosphate (ATP) has been generally accepted
      as the regulator of cellular differentiation, the relative contribution of the
      various purinoreceptor subtypes to purinergic signalling at distinct stages of
      skeletal muscle differentiation is still poorly understood. Here we measured
      extracellular ATP-evoked changes in intracellular calcium concentration and
      surface membrane ionic currents (I (ATP)), calculated the calcium flux (FL)
      entering the myoplasmic space and compared these parameters at different stages
      of differentiation on cultured mouse myotubes. The ATP-evoked FL displayed an
      early peak and then declined to a steady level. With differentiation, the early
      peak became separated from the maintained component and was absent on mature
      myotubes. Repeated ATP applications caused desensitization of the response in
      both immature and differentiated myotubes, owing mainly to the reduction of the
      early peak of FL in the former and to a decline of both components in the latter
      group of cells. Depolarization of the cell or removal of external calcium
      suppressed the early peak. I (ATP) showed no inactivation, and its voltage
      dependence displayed strong inward rectification. The concentration dependence of
      I (ATP) can be fitted using a Hill equation, yielding an EC(50) of 56 microM.
      Results are consistent with the parallel activation of both P2X and P2Y
      receptors.

PMID- 17021796
TI  - CFTR (ABCC7) is a hydrolyzable-ligand-gated channel.
AB  - As the product of the gene mutated in cystic fibrosis, the most common genetic
      disease of Caucasians, CFTR is an atypical ABC protein. From an evolutionary
      perspective, it is apparently a relatively young member of the ABC family,
      present only in metazoans where it plays a critical role in epithelial salt and
      fluid homeostasis. Functionally, the membrane translocation process it mediates,
      the passive bidirectional diffusion of small inorganic anions, is simpler than
      the vectorial transport of larger more complex substrates ("allocrites") by most
      ABC transporters. However, the control of the permeation pathway which cannot go
      unchecked is necessarily more stringent than in the case of the transporters.
      There is tight regulation by the phosphorylation/dephosphorylation of the unique
      CFTR R domain superimposed on the basic ABC regulation mode of ATP binding and
      hydrolysis at the dual nucleotide binding sites. As with other ABCC subfamily
      members, only the second of these sites is hydrolytic in CFTR. The
      phosphorylation and ATP binding/hydrolysis events do not strongly influence each
      other; rather, R domain phosphorylation appears to enable transduction of the
      nucleotide binding allosteric signal to the responding channel gate. ATP
      hydrolysis is not required for either the opening or closing gating transitions
      but efficiently clears the ligand-binding site enabling a new gating cycle to be
      initiated.

PMID- 17021797
TI  - Extracellular zinc stimulates a calcium-activated chloride conductance through
      mobilisation of intracellular calcium in renal inner medullary collecting duct
      cells.
AB  - We have used the perforated patch clamp and fura-2 fluorescence techniques to
      study the effect of extracellular Zn(2+) on whole-cell Ca(2+)-activated Cl(-)
      currents (I (CLCA)) in mouse inner medullary collecting duct cells (mIMCD-3). I
      (CLCA) was spontaneously active in 74% of cells under basal conditions and
      displayed time and voltage-independent kinetics and an outwardly rectifying
      current/voltage relationship (I/V). Addition of zinc chloride (10-400 microM) to
      the bathing solution resulted in a dose-dependent increase in I (CLCA) with
      little change in Cl(-) selectivity or biophysical characteristics, whereas
      gadolinium chloride (30 microM) and lanthanum chloride (100 microM) had no
      significant effect on the whole-cell current. Using fura-2-loaded mIMCD-3 cells,
      extracellular Zn(2+) (400 microM) stimulated an increase in intracellular Ca(2+)
      to an elevated plateau. The Zn(2+)-stimulated [Ca(2+)](i) increase was inhibited
      by thapsigargin (200 nM), the IP(3) receptor antagonist 2-aminoethoxydiphenyl
      borate (10 microM) and removal of bath Ca(2+). Pre-exposure to Zn(2+) (400
      microM) markedly attenuated the ATP (100 microM)-stimulated [Ca(2+)](i) increase.
      These data are consistent with the hypothesis that extracellular Zn(2+)
      stimulates an increase in [Ca(2+)](i) by a release of calcium from
      thapsigargin/IP(3) sensitive stores. A possible physiological role for a divalent
      metal ion receptor, distinct from the extracellular Ca(2+)-sensing receptor, in
      IMCD cells is discussed.

PMID- 17021798
TI  - Cells move when ions and water flow.
AB  - Cell migration is a process that plays an important role throughout the entire
      life span. It starts early on during embryogenesis and contributes to shaping our
      body. Migrating cells are involved in maintaining the integrity of our body, for
      instance, by defending it against invading pathogens. On the other side,
      migration of tumor cells may have lethal consequences when tumors spread
      metastatically. Thus, there is a strong interest in unraveling the cellular
      mechanisms underlying cell migration. The purpose of this review is to illustrate
      the functional importance of ion and water channels as part of the cellular
      migration machinery. Ion and water flow is required for optimal migration, and
      the inhibition or genetic ablation of channels leads to a marked impairment of
      migration. We briefly touch cytoskeletal mechanisms of migration as well as cell
      matrix interactions. We then present some general principles by which channels
      can affect cell migration before we discuss each channel group separately.

PMID- 17021799
TI  - Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of
      chronic beta3-adrenoceptor deficiency.
AB  - This study investigated the influence of chronic beta(3)-adrenoceptor deficiency
      on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins,
      SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild
      type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7).
      Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No
      alterations were observed for the protein expression of the ryanodine receptor or
      phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and
      phospholamban phosphorylation were significantly increased. These changes were
      accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in
      phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)
      adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO.
      Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the
      Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for
      mitochondrial function since the protein expressions of cytochrome c, uncoupling
      protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO.
      The conclusion is that depression of beta(3)-adrenergic stimulation may modulate
      the protein expression of SERCA 2a and phospholamban phosphorylation, thereby
      improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic
      depression may be a therapeutic aim in situations of impaired SERCA 2a activity,
      e.g. for the treatment of heart failure.

PMID- 17021801
TI  - Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes.
AB  - ATP-sensitive potassium (K(ATP)) channels, composed of pore-forming Kir6.2 and
      regulatory sulphonylurea receptor (SUR) subunits, play an essential role in
      insulin secretion from pancreatic beta cells. Binding of ATP to Kir6.2 inhibits,
      whereas interaction of Mg-nucleotides with SUR, activates the channel.
      Heterozygous activating mutations in Kir6.2 (KCNJ11) are a common cause of
      neonatal diabetes (ND). We assessed the functional effects of six novel Kir6.2
      mutations associated with ND: H46Y, N48D, E227K, E229K, E292G, and V252A. K(ATP)
      channels were expressed in Xenopus oocytes and the heterozygous state was
      simulated by coexpression of wild-type and mutant Kir6.2 with SUR1 (the beta cell
      type of SUR). All mutations reduced the sensitivity of the K(ATP) channel to
      inhibition by MgATP, and enhanced whole-cell K(ATP) currents. Two mutations
      (E227K, E229K) also enhanced the intrinsic open probability of the channel,
      thereby indirectly reducing the channel ATP sensitivity. The other four mutations
      lie close to the predicted ATP-binding site and thus may affect ATP binding. In
      pancreatic beta cells, an increase in the K(ATP) current is expected to reduce
      insulin secretion and thereby cause diabetes. None of the mutations substantially
      affected the sensitivity of the channel to inhibition by the sulphonylurea
      tolbutamide, suggesting patients carrying these mutations may respond to these
      drugs.

PMID- 17021802
TI  - Expression of a modified ADP-glucose pyrophosphorylase large subunit in wheat
      seeds stimulates photosynthesis and carbon metabolism.
AB  - ADP-glucose pyrophosphorylase (AGP) is the rate-limiting step in seed starch
      biosynthesis. Expression of an altered maize AGP large subunit (Sh2r6hs) in wheat
      (Triticum aestivum L.) results in increased AGP activity in developing seed
      endosperm and seed yield. The yield phenotype involves increases in both seed
      number and total plant biomass. Here we describe stimulation of photosynthesis by
      the seed-specific Sh2r6hs transgene. Photosynthetic rates were increased in
      Sh2r6hs-expressing plants under high light but not low light growth conditions,
      peaking at roughly 7 days after flowering (DAF). In addition, there were
      significant increases in levels of fructose, glucose, and sucrose in flag leaves
      at both 7 and 14 DAF. In seeds, levels of carbon metabolites at 7 and 14 DAF were
      relatively unchanged but increases in glucose, ADP-glucose, and UDP-glucose were
      observed in seeds from Sh2r6hs positive plants at maturity. Increased
      photosynthetic rates relatively early in seed development appear to be key to the
      Sh2r6hs enhanced yield phenotype as no yield increase or photosynthetic rate
      changes were found when plants were grown in a suboptimal light environment.
      These findings demonstrate that stimulation of biochemical events in both source
      and sink tissues is associated with Sh2r6hs expression.

PMID- 17021803
TI  - Differential expression of the ascorbate oxidase multigene family during fruit
      development and in response to stress.
AB  - Ascorbate oxidase (AO, EC 1.10.3.3) is a member of the multicopper oxidases
      family. It catalyzes the oxidation of ascorbic acid (AA) to dehydroascorbic acid
      (DHA) via monodehydroascorbate (MDHA), with the concomitant reduction of
      molecular oxygen to water. In melon (Cucumis melo), ascorbate oxidase is encoded
      by a multigene family comprising at least four genes. Here, we present the
      detailed characterization of two melon AO genes, CmAO1 and CmAO4. Gene-specific
      expression studies of the AO gene family in melon revealed that only CmAO1 and
      CmAO4 are transcriptionally active and differentially regulated dependent on
      tissue, developmental stage and external stimuli. Transcripts of the CmAO1 gene
      are present in floral and fruit tissues, whereas CmAO4 mRNA preferentially
      accumulates in vegetative tissues. CmAO genes were not detected in melon seeds,
      but CmAO4 expression is activated upon germination. CmAO4 mRNA steady-state
      levels are also regulated in response to wounding and heat stress, by hormones
      (abscisic acid, salicylic acid and jasmonates), AA and copper. These findings
      suggest that AO gene expression is transcriptionally regulated during fruit
      development and in response to hormonal cues associated with the control of cell
      growth and the stress response.

PMID- 17021800
TI  - Twenty odd years of stretch-sensitive channels.
AB  - After formation of the giga-seal, the membrane patch can be stimulated by
      hydrostatic or osmotic pressure gradients applied across the patch. This feature
      led to the discovery of stretch-sensitive or mechanosensitive (MS) channels,
      which are now known to be ubiquitously expressed in cells representative of all
      the living kingdoms. In addition to mechanosensation, MS channels have been
      implicated in many basic cell functions, including regulation of cell volume,
      shape, and motility. The successful cloning, overexpression, and crystallization
      of bacterial MS channel proteins combined with patch clamp and modeling studies
      have provided atomic insight into the working of these nanomachines. In
      particular, studies of MS channels have revealed new understanding of how the
      lipid bilayer modulates membrane protein function. Three major membrane protein
      families, transient receptor potential, 2 pore domain K(+), and the epithelial
      Na(+) channels, have been shown to form MS channels in animal cells, and their
      polymodal activation embrace fields far beyond mechanosensitivity. The discovery
      of new drugs highly selective for MS channels ("mechanopharmaceutics") and the
      demonstration of MS channel involvement in several major human diseases
      ("mechanochannelopathies") provide added motivation for devising new techniques
      and approaches for studying MS channels.

PMID- 17021804
TI  - Comparison of the effects of mechanical and osmotic pressures on the collagen
      fiber architecture of intact and proteoglycan-depleted articular cartilage.
AB  - One of the functions of articular cartilage is to withstand recurrent pressure
      applied in everyday life. In previous studies, osmotic pressure has been used to
      mimic the effects of mechanical pressure. In the present study, the response of
      the collagen network of intact and proteoglycans (PG)-depleted cartilage to
      mechanical and osmotic pressures is compared. The technique used is one
      dimensional (2)H double quantum filtered spectroscopic MRI, which gives
      information about the degree of order and the density of the collagen fibers at
      the different locations throughout the intact tissue. For the nonpressurized
      plugs, the depletion had no effect on these parameters. Major differences were
      found in the zones near the bone between the effects of the two types of
      application of pressure for both intact and depleted plugs. While the order is
      lost in these zones as a result of mechanical load, it is preserved under osmotic
      pressure. For both intact and PG-depleted plugs under osmotic stress most of the
      collagen fibers become disordered. Our results indicate that different modes of
      strain are produced by unidirectional mechanical load and the isotropic osmotic
      stress. Thus, osmotic stress cannot serve as a model for the effect of load on
      cartilage in vivo.

PMID- 17021805
TI  - Quantitative detection of the ligand-dependent interaction between the androgen
      receptor and the co-activator, Tif2, in live cells using two color, two photon
      fluorescence cross-correlation spectroscopy.
AB  - Two-photon, two-color fluorescence cross-correlation spectroscopy (TPTCFCCS) was
      used to directly detect ligand-dependent interaction between an eCFP-fusion of
      the androgen receptor (eCFP-AR) and an eYFP fusion of the nuclear receptor co
      activator, Tif2 (eYFP-Tif2) in live cells. As expected, these two proteins were
      co-localized in the nucleus in the presence of ligand. Analysis of the cross
      correlation amplitude revealed that AR was on average 81% bound to Tif2 in the
      presence of agonist, whereas the fractional complex formation decreased to 56% in
      the presence of antagonist. Residual AR-Tif2 interaction in presence of
      antagonist is likely mediated by its ligand-independent activation function.
      These studies demonstrate that using TPTCFCCS it is possible to quantify ligand
      dependent interaction of nuclear receptors with co-regulator partners in live
      cells, making possible a vast array of structure-function studies for these
      important transcriptional regulators.

PMID- 17021806
TI  - Theoretical evaluation of a possible nature of the outer membrane potential of
      mitochondria.
AB  - A possibility of generation of the outer membrane potential in mitochondria has
      been suggested earlier in the literature, but the potential has not been directly
      measured yet. Even its nature, metabolic impact and a possible range of
      magnitudes are not clear, and require further theoretical and experimental
      analysis. Here, using simple mathematical model, we evaluated a possible
      contribution of the Donnan and metabolically derived potentials to the outer
      membrane potential, concluding that the superposition of both is most probable;
      exclusively Donnan origin of the potential is doubtful because unrealistically
      high concentrations of charged macromolecules are needed for maintaining its
      relatively high levels. Regardless of the mechanism(s) of generation, the maximal
      possible potential seems to be less than 30 mV because significant osmotic
      gradients, created at higher values, increase the probability of the outer
      membrane rupture. New experimental approaches for direct or indirect
      determination of true value of the outer membrane potential are suggested here to
      avoid a possible interference of the surface electrical potential of the inner
      membrane, which may change as a result of the extrusion of matrix protons under
      energization of mitochondria.

PMID- 17021807
TI  - Detection of 99mTc-sestamibi uptake in brown adipose tissue with SPECT-CT.

PMID- 17021808
TI  - Bone involvement in patients with lymphoma: the role of FDG-PET/CT.
AB  - PURPOSE: To evaluate the diagnostic impact and clinical significance of FDG-avid
      bone lesions detected by FDG-PET/CT in patients with lymphoma. METHODS: The study
      population comprised 50 consecutive patients (mean age 41.7+/-15.5 years; 27
      female, 23 male; 41 staging, 9 restaging) with Hodgkin's disease (n=22) or
      aggressive non-Hodgkin's lymphoma (n=28) in whom FDG-avid bone lesions were
      detected by FDG-PET/CT. All patients had either direct biopsy of the FDG-avid
      bone lesion (n=18), standard bone marrow biopsy at the iliac crest (BMB; n=43) or
      both procedures (n=11). In 15 patients, additional MRI of the bone lesions was
      performed. All patients underwent FDG-PET/CT after the end of treatment. All CT
      images of FDG-PET/CT scans were analysed independently regarding morphological
      osseous changes and compared with FDG-PET results. RESULTS: In the 50 patients,
      193 FDG-avid lesions were found by PET/CT. The mean standardised uptake value was
      6.26 (+/-3.22). All direct bone biopsies (n=18) of the FDG-avid lesions proved
      the presence of lymphomatous infiltration. BMB (n=43) was positive in 12 patients
      (27.9%). In CT, 32 of 193 (16.6%) lesions were detected without the PET
      information. No additional morphological bone infiltration was detected on CT
      compared with FDG-PET. All morphological bone alterations on CT scans persisted
      after the end of therapy. Additional PET/CT information regarding uni- or
      multifocal bone involvement resulted in lymphoma upstaging in 21 (42%) patients
      compared with the combined information provided by CT and BMB. CONCLUSION: In
      patients with FDG-avid bone lesions, FDG-PET is superior to CT alone or in
      combination with unilateral BMB in detecting bone marrow involvement, leading to
      upstaging in a relevant proportion of patients.

PMID- 17021809
TI  - Myocardial sympathetic innervation in patients with chronic coronary artery
      disease: is reduction in coronary flow reserve correlated with sympathetic
      denervation?
AB  - PURPOSE: Higher sensitivity of sympathetic nerves to ischaemia in comparison with
      myocytes has been observed and has been claimed to contribute to poor prognosis
      in patients with coronary artery disease (CAD). The aim of this study was to
      evaluate the dependency of myocardial sympathetic innervation on restrictions in
      coronary flow reserve (CFR). METHODS: We analysed 27 non-diabetic patients with
      advanced CAD. We determined quantitative myocardial blood flow using (13)N
      ammonia PET, myocardial viability with (18)F-FDG PET and cardiac innervation with
      (11)C-HED PET. Scarred segments were excluded from analysis. We investigated the
      relationship between regional HED retention, blood flow and CFR. RESULTS: There
      was no correlation between rest perfusion and HED retention within a flow range
      from approximately 30 to 120 ml/(100 ml x min). A slight correlation was observed
      between stress perfusion values and HED retention (p<0.001), and between CFR and
      HED retention (p<0.001). CONCLUSION: In non-diabetic CAD patients, HED retention
      in vital myocardium does not correlate with myocardial rest perfusion over a
      large flow range. The observed relation between HED retention and CFR indicates
      that sympathetic innervation can be preserved even when there is major impairment
      of myocardial blood supply. Most probably the occurrence of denervation depends
      not only on reductions in CFR, but also on the duration and severity of resulting
      ischaemic episodes.

PMID- 17021810
TI  - FDG PET as a predictor of response to resynchronisation therapy in patients with
      ischaemic cardiomyopathy.
AB  - PURPOSE: Although resynchronisation therapy (CRT) is a promising addition to
      heart failure therapy, a substantial number of patients do not respond to CRT. As
      FDG PET has routinely been used for prediction of improvement after
      revascularisation in ischaemic cardiomyopathy, it was hypothesised that there is
      also a relationship between the extent of viable tissue and improvement as a
      result of CRT. METHODS: Thirty-nine patients with ischaemic cardiomyopathy
      (ejection fraction 27 +/- 9%) and a wide QRS complex underwent temporary pacing
      to determine the optimal pacing combination, i.e. that with the highest increase
      in cardiac index (CI) compared with baseline (measured by Doppler
      echocardiography). All patients also underwent FDG PET imaging. In 19 patients,
      CI measurements were repeated 10-12 weeks after permanent biventricular pacemaker
      implantation. RESULTS: Echocardiography (13-segment model) showed a mean of 9.8
      +/- 1.6 dyssynergic segments, with preserved FDG uptake in 4.1 +/- 2.4 segments.
      CI improvement at the optimal pacing site was 20 +/- 9%. There was a linear
      relationship between the extent of viable tissue and CI improvement during pacing
      (p < 0.001). Using a cut-off value of more than three viable segments (ROC
      analysis), FDG PET had a sensitivity of 72% and a specificity of 71% for
      detection of the presence of haemodynamic improvement (i.e. a CI improvement
      >15%). The relation between CI improvement and viable tissue was similar at
      follow-up. CONCLUSION: A correlation was found between the extent of viable
      tissue and the haemodynamic response to CRT in patients with ischaemic
      cardiomyopathy, suggesting that FDG PET imaging may be useful to discriminate
      between responders and non-responders to CRT.

PMID- 17021811
TI  - Change in the intrathyroidal kinetics of radioiodine under continued and
      discontinued antithyroid medication in Graves' disease.
AB  - PURPOSE: This study evaluated the thyroidal kinetics of radioiodine in Graves'
      disease under continued thiamazole medication and after discontinuation of
      thiamazole for 1-2 days, with a view to keeping the period of discontinuation as
      short as possible and to exploring the underlying mechanism of a postulated
      radioprotective effect of antithyroid drugs. METHODS: In 316 patients, diagnostic
      and therapeutic radioiodine kinetics were followed up for 2 days by ten uptake
      measurements each and were defined mathematically by a two-compartment model.
      RESULTS: Without thiamazole or when thiamazole was discontinued for at least 2
      days, all uptake curves could be fitted perfectly by a simple in- and output
      function; the mean square error (mse) was 0.38 (test) and 0.28 (therapy). Under
      continued thiamazole medication (11.0+/-7.0 mg/day), the energy dose delivered to
      the thyroid was lowered by factor of 2.5. Uptake curves were deformed (mse: 1.06,
      test and 0.86, therapy) and appeared two peaked, suggesting coexistence of
      follicles with blocked and follicles with intact hormone synthesis and hence
      heterogeneous radioiodine uptake in the thyroid. In patients with maximally
      altered uptake curves, the success rate was as low as 31%. One day after
      discontinuation of thiamazole, mse was still increased (0.78, test), while 2 days
      afterwards it had normalised (0.36, test) and 3 days afterwards (mse: 0.24,
      therapy) the success rate was 87%. CONCLUSION: Efficacy of radioiodine therapy
      under continued thiamazole medication is reduced not only by a lower uptake and
      shorter half-life of radioiodine, but also by a heterogeneous energy dose
      distribution in the thyroid. Discontinuation of thiamazole (but probably not of
      propylthiouracil) for at least 2 days is required to restore the efficacy of
      radioiodine.

PMID- 17021812
TI  - Long-term toxicity of [(177)Lu-DOTA (0),Tyr (3)]octreotate in rats.
AB  - PURPOSE AND METHODS: Studies on peptide receptor radionuclide therapy (PRRT)
      using radiolabelled somatostatin analogues have shown promising results with
      regard to tumour control. The efficacy of PRRT is limited by uptake and retention
      in the proximal tubules of the kidney, which might lead to radiation nephropathy.
      We investigated the long-term renal toxicity after different doses of [(177)Lu
      DOTA(0),Tyr(3)]octreotate and the effects of dose fractionation and lysine co
      injection in two tumour-bearing rat models. RESULTS: Significant renal toxicity
      was detected beyond 100 days after start of treatment as shown by elevated serum
      creatinine and proteinuria. Microscopically, tubules were strongly dilated with
      flat epithelium, containing protein cylinders. Creatinine levels rose
      significantly after 555 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate, but were
      significantly lower after 278 MBq (single injection) or two weekly doses of 278
      MBq. Renal damage scores were maximal after 555 MBq and significantly lower in
      the 278 and 2x278 MBq groups. Three doses of 185 MBq [(177)Lu
      DOTA(0),Tyr(3)]octreotate with intervals of a day, a week or a month
      significantly influenced serum creatinine (469+/-18, 134+/-70 and 65+/-15
      micromol/l, respectively; p<0.001). Renal histological damage scores were not
      significantly influenced by dose fractionation. Lysine co-administration with
      three weekly treatments of 185 MBq significantly lowered serum creatinine and
      proteinuria. CONCLUSION: Injection of high doses of [(177)Lu
      DOTA(0),Tyr(3)]octreotate resulted in severe renal damage in rats as indicated by
      proteinuria, elevated serum creatinine and histological damage. This damage was
      dose dependent and became overt between 100 and 200 days after treatment. Dose
      fractionation had significant beneficial effects on kidney function. Also, lysine
      co-injection successfully prevented functional damage.

PMID- 17021813
TI  - Distribution of the 5-HT(1A) receptor antagonist [ (18)F]FPWAY in blood and brain
      of the rat with and without isoflurane anesthesia.
AB  - PURPOSE: To determine whether brain and plasma equilibrium of a proposed PET
      tracer for 5-HT(1A), [(18)F]FPWAY, can be achieved in a sufficiently short time
      for practical use of the brain to plasma equilibrium distribution ratio (DR) to
      monitor receptor availability with and without isoflurane anesthesia. METHODS:
      Awake (n=4) and isoflurane-anesthetized (n=4) rats were administered a continuous
      60 min intravenous infusion of [(18)F]FPWAY with timed arterial blood sampling.
      Brains of the isoflurane-anesthetized rats were scanned with the ATLAS small
      animal PET scanner; awake rats were not. All rats were killed at 60 min and
      scanned postmortem for 15 min, followed by brain slicing for autoradiography.
      Several regions of interest (ROIs) were defined in the PET images as well as in
      the autoradiographic images. Regional DRs were calculated as total activity in
      the brain ROI divided by plasma [(18)F]FPWAY activity. RESULTS: DRs in the
      anesthetized animals were constant between 30 and 60 min, indicating that near
      equilibrium between brain and plasma had been achieved by approximately 30 min.
      DRs determined from postmortem PET data were higher in the isoflurane
      anesthetized rats by 24% (not significant) and 33% (p=0.065) in whole brain and
      hippocampus, respectively. DRs determined from autoradiographic data were greater
      in isoflurane-anesthetized rats in medial hippocampus, lateral hippocampus, and
      cerebellum by 33% (p=0.054), 63% (p<0.01), and 32% (p<0.05), respectively.
      CONCLUSION: [(18)F]FPWAY could be an appropriate ligand for monitoring changes in
      receptor availability in the serotonergic system using a bolus/infusion paradigm.
      One possible explanation for higher DRs in anesthetized rats may be a reduction
      in endogenous 5-HT secretion under isoflurane anesthesia.

PMID- 17021814
TI  - Reproducibility of whole-body 131I scan and serum thyrotropin and stimulated
      thyroglobulin values in patients studied twice after injection of recombinant
      human thyrotropin.
AB  - PURPOSE: Recombinant human TSH (rhTSH) is used to increase radioiodine uptake
      during imaging of thyroid cancer, obviating the need to render the patient
      hypothyroid. We assessed the reproducibility of radioiodine uptake, serum
      thyrotropin (TSH), and stimulated serum thyroglobulin (Tg) levels after rhTSH
      administration. METHODS: A retrospective review was performed of patients at
      Stanford who underwent whole-body (131)I scanning for surveillance of thyroid
      cancer twice after thyroidectomy and (131)I ablation, with rhTSH prior to each
      scan. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum
      Tg levels for each study were recorded. Paired t tests and correlation analysis
      were used to assess interexamination repeatability. RESULTS: Twenty-three
      patients underwent two scintiscans with rhTSH, for a total of 46 exams. There was
      no significant difference between percent uptake at 48 h in the paired exams
      (p=0.40). Serum TSH level was measured in 45 of 46 exams; TSH exceeded 50 mIU/l
      in all cases, and there was no significant difference between paired TSH levels
      (p=0.93). All patients had stimulated serum Tg levels measured, with no
      significant difference between paired Tg levels (p=0.40); after excluding one
      patient whose Tg changed from 15.8 ng/ml to undetectable between scans without
      interval treatment, the p value rose to 0.95. There was a strong correlation
      among paired uptake values (r=0.85, p<0.0001), peak serum TSH (r=0.69, p=0.0003),
      and stimulated Tg levels (r=0.81, p<0.0001). No discordant scan interpretations
      were reported. CONCLUSION: Forty-eight hour radioiodine uptake, peak serum TSH,
      and stimulated serum Tg levels after administration of rhTSH are repeatable
      between studies, demonstrating reproducibility of diagnostic results without
      rendering patients hypothyroid.

PMID- 17021815
TI  - Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted
      mice.
AB  - PURPOSE: Pretargeting with phosphorodiamidate morpholino oligomers (MORFs)
      involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as
      a pretargeting agent before that of the radiolabeled complementary MORF (cMORF)
      as the effector. The dosages of the pretargeting agent and effector, the
      pretargeting interval, and the detection time are the four pretargeting
      variables. The goal of this study was to develop a semiempirical description
      capable of predicting the biodistribution of the radiolabeled effector in
      pretargeted mice and then to compare predictions with experimental results from
      pretargeting studies in tumored animals in which the pretargeting interval and
      the detection time were both fixed but the dosages of both the effector and the
      pretargeting agent were separately varied. METHODS: Pretargeting studies in
      LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated
      with MORF and the cMORF radiolabeled with (99m)Tc. A description was developed
      based on our previous observations in the same mouse model of the blood and tumor
      levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor
      accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the
      kidney accumulation of labeled cMORF. The predicted values were then compared
      with the experimental values. RESULTS: The predicted biodistribution of the
      radiolabeled effector and the experimental data were in gratifying agreement in
      normal organs, suggesting that the description of the pretargeting process was
      reliable. The tumor accumulations occasionally fell outside two standard
      deviations of that predicted, but after tumor size correction, good agreement
      between predicted and experimental values was observed here as well. CONCLUSION:
      A semiempirical description of the biodistribution of labeled cMORF was capable
      of predicting the biodistribution of the radiolabeled effector in the pretargeted
      tumored mouse model, demonstrating that the underlying pretargeting concepts are
      correct. We believe that the approach described herein may be applied to any of
      the alternative pretargeting approaches and animal tumor models currently under
      investigation. Furthermore, appreciation of the concepts may provide a rationale
      for selecting dosages and timings in human pretargeting studies as an alternative
      to pure empirical means.

PMID- 17021816
TI  - PET imaging of apoptosis with (64)Cu-labeled streptavidin following pretargeting
      of phosphatidylserine with biotinylated annexin-V.
AB  - PURPOSE: In vivo detection of apoptosis is a diagnostic tool with potential
      clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV)
      is an ideal probe for in vivo apoptosis detection owing to its strong affinity
      for phosphatidylserine (PS), the molecular flag on the surface of apoptotic
      cells. Most clinical studies performed to visualize apoptosis have used (99m)Tc
      anxV; however, its poor distribution profile often compromises image quality. In
      this study, tumor apoptosis after therapy was visualized by positron emission
      tomography (PET) using (64)Cu-labeled streptavidin (SAv), following pre-targeting
      of apoptotic cells with biotinylated anxV. METHODS: Apoptosis was induced in
      tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as
      photosensitizers, and red light. After PDT, mice were injected i.v. with
      biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h
      with (64)Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h
      after PDT. RESULTS: PET images delineated apoptosis in treated tumors as early as
      30 min after (64)Cu-DOTA-biotin-SAv administration, with tumor-to-background
      ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the
      administration of biotinylated anxV or the avidin chase failed to provide a clear
      PET image, confirming that all three steps are essential for adequate
      visualization of apoptosis. Furthermore, differences in action mechanisms between
      photosensitizers that target tumor cells directly or via initial vascular stasis
      were clearly recognized through differences in tracer uptake patterns detecting
      early or delayed apoptosis. CONCLUSION: This study demonstrates the efficacy of a
      three-step (64)Cu pretargeting procedure for PET imaging of apoptosis. Our data
      also confirm the usefulness of small animal PET to evaluate cancer treatment
      protocols.

PMID- 17021817
TI  - Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL.
AB  - PURPOSE: To evaluate the feasibility of using (99m)Tc-glutamate peptide-estradiol
      in functional imaging of estrogen receptor-positive [ER(+)] diseases. METHODS: 3
      Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP
      EDL. Cellular uptake studies of (99m)Tc-GAP-EDL were conducted in ER(+) cell
      lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP
      kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells.
      Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h.
      Each rat was administered (99m)Tc-GAP-EDL. Two animal models (rats and rabbits)
      were created to ascertain whether tumor uptake of (99m)Tc-GAP-EDL was via an ER
      mediated process. In the tumor model, breast tumor-bearing rats were pretreated
      with diethylstilbestrol (DES) 1 h prior to receiving (99m)Tc-GAP-EDL. In the
      endometriosis model, part of the rabbit uterine tissue was dissected and grafted
      to the peritoneal wall. The rabbit was administered with (99m)Tc-GAP-EDL.
      RESULTS: There was a 10-40% reduction in uptake of (99m)Tc-GAP-EDL in cells
      treated with DES or tamoxifen compared with untreated cells. Western blot
      analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution
      studies showed that tumor uptake and tumor-to-muscle count density ratio in
      (99m)Tc-GAP-EDL groups were significantly higher than those in (99m)Tc-GAP groups
      at 4 h. Among (99m)Tc-GAP-EDL groups, region of interest analysis of images
      showed that tumor-to muscle ratios were decreased in blocking groups. In the
      endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc
      GAP-EDL. CONCLUSION: Cellular or tumor uptake of (99m)Tc-GAP-EDL occurs via an ER
      mediated process. (99m)Tc-GAP-EDL is a useful agent for imaging functional ER(+)
      disease.

PMID- 17021818
TI  - 123I-labeled HIV-1 tat peptide radioimmunoconjugates are imported into the
      nucleus of human breast cancer cells and functionally interact in vitro and in
      vivo with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).
AB  - PURPOSE: To evaluate the internalization and nuclear translocation of (123)I-tat
      peptide radioimmunoconjugates in MDA-MB-468 breast cancer cells and their ability
      to interact with the cyclin-dependent kinase inhibitor, p21(WAF-1/Cip-1).
      METHODS: Peptides [GRKKRRQRRRPPQGYGC] harboring the nuclear-localizing sequence
      from HIV tat domain were conjugated to anti-p21(WAF-1/Cip-1) antibodies.
      Immunoreactivity was assessed by Western blot using lysate from MDA-MB-468 cells
      exposed to EGF to induce p21(WAF-1/Cip-1). Internalization and nuclear
      translocation were measured. The ability of tat-anti-p21(WAF-1/Cip-1) to block
      G(1)-S phase arrest in MDA-MB-468 cells caused by EGF-induced p21(WAF-1/Cip-1)
      was evaluated. Tumor and normal tissue uptake were determined at 48 h p.i. in
      athymic mice implanted s.c. with MDA-MB-468 xenografts injected intratumorally
      with EGF. RESULTS: There was 13.4+/-0.2% of radioactivity internalized by MDA-MB
      468 cells incubated with (123)I-tat-anti-p21(WAF-1/Cip-1) and 34.6+/-3.1%
      imported into the nucleus. Tat-anti-p21(WAF-1/Cip-1)(8 muM) decreased the
      proportion of EGF-treated cells in G(1) phase from 81.9+/-0.7% to 46.1+/-0.7%
      (p<0.001), almost restoring the G(1) phase fraction to that of unexposed cells
      (25.8+/-0.2%). Non-specific tat-mouse IgG did not block EGF-induced G(1)-S phase
      arrest. Tumor uptake of radioactivity was higher in mice injected with EGF to
      induce p21(WAF-1/Cip-1) than in mice not receiving EGF (3.1+/-0.4% versus 1.8+/
      0.2% ID/g; p=0.04). Western blot analysis of tumors revealed a threefold increase
      in the p21(WAF-1/Cip-1)/beta-actin ratio. CONCLUSION: We conclude that
      intracellular and nuclear epitopes in cancer cells can be functionally targeted
      with tat-radioimmunoconjugates to exploit many more epitopes for imaging and
      radiotherapeutic applications than have previously been accessible.

PMID- 17021819
TI  - Class III beta-tubulin is a marker of paclitaxel resistance in carcinomas of
      unknown primary site.
AB  - PURPOSE: In this study, we determine the prevalence and the prognostic value of
      the class III beta-tubulin microtubule protein examined immunohistochemically, in
      tumors of 40 patients with carcinomas of unknown primary site treated with
      paclitaxel-based chemotherapy. METHODS: Immunohistochemical intensity of staining
      and percentage of cells were quantified. Clinical characteristics, response to
      chemotherapy, progression-free survival, and overall survival were assessed for
      relationships with the expression of class III beta-tubulin. RESULTS: The
      response rate was 17.9% (seven partial responses among 39 valuable patients),
      while eleven patients had a stable disease (28.2%) and 21 patients progressed on
      therapy (53.8%). Patients with high class III beta-tubulin expression were more
      resistant to taxane-based chemotherapy, defined as progression under treatment,
      while patient characteristics were not found to be correlated with response to
      chemotherapy. Patients whose tumors expressed high levels of class III beta
      tubulin isotype had shorter overall survival, while there was a trend for an
      association with progression free survival. Multivariate analysis showed that
      class III beta-tubulin expression was independently correlated with progression
      free survival and overall survival. CONCLUSIONS: These findings suggest that a
      high level of expression of class III beta-tubulin in tumor cells is associated
      with resistance to paclitaxel and decreased survival in patients with carcinomas
      of unknown primary receiving paclitaxel-based chemotherapy.

PMID- 17021820
TI  - Platinum drug effects on the expression of genes in the polyamine pathway: time
      course and concentration-effect analysis based on Affymetrix gene expression
      profiling of A2780 ovarian carcinoma cells.
AB  - PURPOSE: As a follow-up to our previous findings that platinum drugs induce a key
      enzyme in polyamine catabolism, gene expression profiling and mathematical
      modeling were used to define the effects of cisplatin and oxaliplatin on the
      expression of polyamine metabolic pathway genes in A2780 human ovarian carcinoma
      cells. METHODS: Time-course and concentration-effect experiments were each
      carried out with cisplatin or oxaliplatin in two separate experiments and cells
      subjected to gene expression profiling using Affymetrix array technology. Time
      course data were modeled using exponential increase and decrease models.
      Concentration-effect data were modeled using a four parameter Hill model.
      RESULTS: Gene expression profiling of human ovarian carcinoma A2780 cells after
      exposure to either cisplatin or oxaliplatin indicates that the expression of
      several genes involved in polyamine pathway is affected by the platinum drugs.
      Mathematical/Statistical modeling of the data from time-course and concentration
      effect experiments of gene expression from nine polyamine pathway genes
      represented on the HGU95Av2 chip, indicates that three biosynthetic pathway genes
      (SAMDC, ODC1 and SRM) are down-regulated and one catabolic pathway gene (SSAT) is
      up-regulated. Expression changes were similar for different probesets for a given
      gene on the array. Studies on the induction of SSAT by platinum drugs suggested
      by the Affymetrix data have been previously validated from this laboratory
      (Hector et al. in Mol Cancer Ther 3:813-822, 2004). Here, the effects of
      oxaliplatin exposure on SAMDC and ODC observed by Affymetix are validated with
      real time QRT-PCR. CONCLUSION: The data indicate a concerted effect of platinum
      drugs on the polyamine metabolic pathway with down-regulation in the expression
      of several enzyme genes involved in biosynthesis and many-fold up-regulation in
      expression of SSAT, an acetylating enzyme gene that is critically involved in
      polyamine catabolism and export.

PMID- 17021821
TI  - Oral vinorelbine/paclitaxel combination treatment of metastatic breast cancer: a
      phase I study.
AB  - PURPOSE: Intravenous (i.v.) vinorelbine (VRL) generally given on days 1 and 8 of
      an every three-week cycle in combination with paclitaxel (PTX) is an effective
      option for the treatment of metastatic breast cancer (MBC). In an effort to
      improve both patient and chemotherapy unit convenience, oral VRL was used at
      equivalent doses of i.v. VRL. PATIENTS AND METHODS: The maximal tolerated dose
      (MTD) was determined during the first cycle of oral VRL given on days 1 and 8 or
      15 and PTX infused over 3 h on day 1 every 3 weeks, maximum of 6 cycles. The dose
      of oral VRL was escalated from 60 to 80 mg/m2 in 10 mg/m2 increments. Paclitaxel
      was administered at 110 and then 135 mg/m2. The combination regimen was given as
      first-line chemotherapy of MBC. Three to six patients per cohort were treated.
      RESULTS: Twenty-two patients were treated in the first four cohorts (oral
      VRL/PTX): 60/110, 70/110, 80/110 and 80/135. In cohort 4, seven patients were
      treated, one patient being non-evaluable for MTD, three of them presented a dose
      limiting toxicity (DLT) consisting of febrile neutropenia and neutropenic
      infection. Therefore 80/135 was the MTD. Because 36% of oral VRL administrations
      on day 8 were delayed to day 15 at 80/110, two additional cohorts were tested: in
      cohort 5, oral VRL 60 mg/m2 on days 1 and 15 and PTX 135 mg/m2 on day 1 and in
      cohort 6, oral VRL 80 mg/m2 on days 1 and 15 and PTX 110 mg/m2 on day 1, every 3
      weeks. In cohort 5, six out of eight patients had DLTs: omission of oral VRL on
      day 15 for five patients, grade 4 neutropenia>7 days for another one. Therefore
      the recommended dose (RD) for further clinical testing was oral VRL 80 mg/m2 on
      days 1 and 15 and PTX 110 mg/m2 on day 1 of an every 3-week cycle. Two of the
      three evaluable patients treated at the RD had a partial response. The
      pharmacokinetics of VRL and PTX is being analysed and will be further presented
      in a separate publication. CONCLUSIONS: This phase I study has determined the
      doses of oral VRL and PTX to be used in combination for the benefit of the
      patient and of the chemotherapy unit in term of nurse's workload. The recommended
      regimen of oral VRL 80 mg/m2 on days 1 and 15 and PTX 110 mg/m2 on day 1 given
      every 3 weeks will be further tested in phase II.

PMID- 17021822
TI  - Pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid (AS1404), a novel
      vascular disrupting agent, in phase I clinical trial.
AB  - PURPOSE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) (AS1404) is a novel
      antitumour agent that selectively disrupts tumour vasculature and induces
      cytokines. The purpose of this study was to determine the pharmacokinetics (PK)
      of DMXAA in cancer patients enrolled in a phase I clinical trial. METHODS: DMXAA
      was administered as a 20-min i.v. infusion every 3 weeks and doses were escalated
      in cohorts of patients according to a predefined schema. PK samples were taken
      over the first 24 h of at least the first cycle. RESULTS: DMXAA was administered
      to 63 patients at 19 dose levels from 6 to 4,900 mg m(-2), and 3,700 mg m(-2) was
      established as the maximum tolerated dose. The PK observed over the dose range
      showed a non-linear fall in clearance from 16.1 to 1.42 l h(-1) m(-2) and
      resultant increase in the area under the concentration-time curve (AUC) from 1.29
      to 12,400 microM h. In contrast, the increase in peak plasma concentrations from
      2.17 to 1,910 microM approximated linearity. DMXAA was highly protein-bound to
      albumin (>99%) until saturation occurred at higher doses, leading to a rapid
      increase in the free fraction (up to 20%) and greater concentrations of DMXAA
      bound to non-albumin proteins. However, the main determinant of the non-linearity
      of the PK appeared to be sequential saturation of elimination mechanisms, which
      include hydroxylation, glucuronidation and perhaps hepatic transport proteins.
      This resulted in an exaggerated non-linear increase in free DMXAA plasma
      concentrations and AUC compared to total drug. CONCLUSIONS: The PK of DMXAA are
      well-defined, with a consistent degree of non-linearity across a very large dose
      range.

PMID- 17021823
TI  - Treatment options for BCG failures.

PMID- 17021824
TI  - Association of EMMPRIN and fascin expression in renal cell carcinoma: correlation
      with clinicopathological parameters.
AB  - EMMPRIN and fascin are important factors in tumor invasion and progression. We
      tested the hypothesis that expression of EMMPRIN and fascin correlate with
      clinicopathological parameters of renal cell carcinoma (RCC). Immunohistochemical
      analysis of EMMPRIN and fascin were performed in tissue microarrays of 100
      surgical specimens, including 35 clear-cell RCC (CRCC), 21 clear-cell RCC with
      granular differentiation (GRCC), 12 chromophobe RCC (ChRCC), 8 papillary RCC
      (PRCC), 9 carcinoma of the collecting duct of Bellini (CDC), 10 clear-cell RCC
      with sarcomatoid differentiation (SRCC), and 6 metastatic RCC. Average
      immunoscores of EMMPRIN were 100.8 in CRCC, 195.2 in GRCC, 298.4 in ChRCC, 219.2
      in PRCC, 186.1 in CDC, 226.9 in SRCC, and 151.7 in metastatic RCC. Among all
      included cases, average EMMPRIN immunoscores were 84.6 in grade I, 130.4 in grade
      II, 184.3 in grade III, and 223.5 in grade IV. Additionally, average
      immunostaining scores of fascin were 53.6 in CRCC, 289.3 in GRCC, 193.3 in ChRCC,
      151.8 in PRCC, 181.3 in CDC, 275.4 in SRCC, and 131.7 in metastatic RCC. Average
      fascin immunoscores were 59.3 in grade I, 91.6 in grade II, 130.2 in grade III,
      and 194.7 in grade IV. Higher EMMPRIN and fascin immunoscores also correlated
      significantly with TNM stages and survival rates in RCC. Significant correlation
      was found between EMMPRIN and fascin expression. In conclusion, higher expression
      of EMMPRIN and fascin correlate significantly with histological grades, clinical
      stages, and survival rates of RCC.

PMID- 17021825
TI  - False-positive lesions detected by fluorescence cystoscopy: any association with
      p53 and p16 expression?
AB  - To determine p53 and p16 status as molecular markers of bladder cancer, in
      histologically proven benign bladder biopsies, obtained from lesions suspect for
      malignancy as judged by fluorescence cystoscopy. Immunohistochemical (IHC)
      staining was performed for p53 and p16, using the antibodies DO-7 and AB-4,
      respectively. The tissue sections were scored in percentages of nuclear staining
      for p53 and p16. Of 247 biopsies, 41/49 lesions appeared suspicious on
      fluorescence cystoscopy, but were histopathologically benign. 2/40 (5%) were > or
      =20% p53 positive as compared to 7/128 (5.5%) of all histopathologically benign
      biopsies. 24/37 (64.9%) were p16 negative (<5% positive cells) as compared to
      84/125 (67.2%) of all benign biopsies. Most biopsies had a moderate to high
      degree of chronic cystitis. False positive lesions of fluorescence cystoscopy did
      not differ from benign lesions detected by standard white light cystoscopy with
      regard to p53 and p16 immunoreactivity. Little evidence remains for these lesions
      to be pre-malignant.

PMID- 17021826
TI  - Chemopreventive property of dietary ginger in rat urinary bladder chemical
      carcinogenesis.
AB  - The modifying potential of ginger on the development of preneoplasia and tumors
      in the male Wistar rat urinary bladder was investigated in a 36-week-long
      initiation-promotion assay for chemical carcinogenesis. Groups G1 to G3 were
      given 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in drinking water for 5
      weeks and a 3% uracil meal for the subsequent 3 weeks. Groups G4 and G5 were
      treated with 3% uracil only for the same period. After these steps, groups G2,
      and G3 and G4 were fed for 26 weeks a ginger extract mixed at 0.5 and 1.0% in a
      basal diet, respectively. Thirty six weeks after the beginning of the experiment
      all rats were killed. The multiplicity of urothelial lesions (hyperplasia and
      neoplasia) was significantly lower (P = 0.013) in group G3 than in groups G1 and
      G2. The results suggest that 1.0% ginger meal exerts a protective effect on the
      post-initiation stage of rat chemically-induced urothelial carcinogenesis.

PMID- 17021827
TI  - Local visual homing by matched-filter descent in image distances.
AB  - In natural images, the distance measure between two images taken at different
      locations rises smoothly with increasing distance between the locations. This
      fact can be exploited for local visual homing where the task is to reach a goal
      location that is characterized by a snapshot image: descending in the image
      distance will lead the agent to the goal location. To compute an estimate of the
      spatial gradient in the distance measure, its value must be sampled at three
      noncollinear points. An animal or robot would have to insert exploratory
      movements into its home trajectory to collect these samples. Here we suggest a
      method based on the matched-filter concept that allows one to estimate the
      gradient without exploratory movements. Two matched filters--optical flow fields
      resulting from translatory movements in the horizontal plane--are used to predict
      two images in perpendicular directions from the current location. We investigate
      the relation to differential flow methods applied to the local homing problem and
      show that the matched-filter approach produces reliable homing behavior on image
      databases. Two alternative methods that only require a single matched filter are
      suggested. The matched-filter concept is also applied to derive a home-vector
      equation for a Fourier-based parameter method.

PMID- 17021828
TI  - Principal dynamic mode analysis of action potential firing in a spider
      mechanoreceptor.
AB  - The encoding of mechanical stimuli into action potentials in two types of spider
      mechanoreceptor neurons is modeled by use of the principal dynamic modes (PDM)
      methodology. The PDM model is equivalent to the general Wiener-Bose model and
      consists of a minimum set of linear dynamic filters (PDMs), followed by a
      multivariate static nonlinearity and a threshold function. The PDMs are obtained
      by performing eigen-decomposition of a matrix constructed using the first-order
      and second-order Volterra kernels of the system, which are estimated by means of
      the Laguerre expansion technique, utilizing measurements of pseudorandom
      mechanical stimulation (input signal) and the resulting action potentials (output
      signal). The static nonlinearity, which can be viewed as a measure of the
      probability of action potential firing as a function of the PDM output values, is
      computed as the locus of points of the latter that correspond to output action
      potentials. The performance of the model is assessed by computing receiver
      operating characteristic (ROC) curves, akin to the ones used in decision theory
      and quantified by computing the area under the ROC curve. Three PDMs are revealed
      by the analysis. The first PDM exhibits a high-pass characteristic, illustrating
      the importance of the velocity of slit displacement in the generation of action
      potentials at the mechanoreceptor output, while the second and third PDMs exhibit
      band-pass and low-pass characteristics, respectively. The corresponding three
      input nonlinearity exhibits asymmetric behavior with respect to its arguments,
      suggesting directional dependence of the mechanoreceptor response on the
      mechanical stimulation and the PDM outputs, in agreement to our findings from a
      previous study (Ann Biomed Eng 27:391-402, 1999). Differences between the Type A
      and B neurons are observed in the zeroth-order Volterra kernels (related to the
      average firing), as well as in the magnitudes of the second and third PDMs that
      perform band-pass and low-pass processing of the input signal, respectively.

PMID- 17021829
TI  - Response linearity determined by recruitment strategy in detailed model of
      nictitating membrane control.
AB  - Many models of eyeblink conditioning assume that there is a simple linear
      relationship between the firing patterns of neurons in the interpositus nucleus
      and the time course of the conditioned response (CR). However, the complexities
      of muscle behaviour and plant dynamics call this assumption into question. We
      investigated the issue by implementing the most detailed model available of the
      rabbit nictitating membrane response (Bartha and Thompson in Biol Cybern 68:135
      143, 1992a and in Biol Cybern 68:145-154, 1992b), in which each motor unit of the
      retractor bulbi muscle is represented by a Hill-type model, driven by a non
      linear activation mechanism designed to reproduce the isometric force
      measurements of Lennerstrand (J Physiol 236:43-55, 1974). Globe retraction and NM
      extension are modelled as linked second order systems. We derived versions of the
      model that used a consistent set of SI units, were based on a physically
      realisable version of calcium kinetics, and used simulated muscle cross-bridges
      to produce force. All versions showed similar non-linear responses to two basic
      control strategies. (1) Rate-coding with no recruitment gave a sigmoidal relation
      between control signal and amplitude of CR, reflecting the measured relation
      between isometric muscle force and stimulation frequency. (2) Recruitment of
      similar strength motor units with no rate coding gave a sublinear relation
      between control signal and amplitude of CR, reflecting the increase in muscle
      stiffness produced by recruitment. However, the system response could be
      linearised by either a suitable combination of rate-coding and recruitment, or by
      simple recruitment of motor units in order of (exponentially) increasing
      strength. These plausible control strategies, either alone or in combination,
      would in effect present the cerebellum with the simplified virtual plant that is
      assumed in many models of eyeblink conditioning. Future work is therefore needed
      to determine the extent to which motor neuron firing is in fact linearly related
      to the nictitating membrane response.

PMID- 17021830
TI  - Sensitivity to interaural time difference and representation of azimuth in
      central nucleus of inferior colliculus in the barn owl.
AB  - Standard electrophysiology and virtual auditory stimuli were used to investigate
      the influence of interaural time difference on the azimuthal tuning of neurons in
      the core and the lateral shell of the central nucleus of the inferior colliculus
      of the barn owl. The responses of the neurons to virtual azimuthal stimuli
      depended in a periodic way on azimuth. Fixation of the interaural time
      difference, while leaving all other spatial cues unchanged, caused a loss of
      periodicity and a broadening of azimuthal tuning. This effect was studied in more
      detail in neurons of the core. The azimuthal range tested and the frequency
      selectivity of the neurons were additional parameters influencing the changes
      induced by fixating the interaural time difference. The addition of an interaural
      time difference to the virtual stimuli resulted in a shift of the tuning curves
      that correlated with the interaural time difference added. In this condition,
      tuning strength did not change. These results suggest that interaural time
      difference is an important determinant of azimuthal tuning in all neurons of the
      core and lateral shell of the central nucleus of the inferior colliculus, and is
      the only determinant in many of the neurons from the core.

PMID- 17021831
TI  - Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa.
AB  - Although chemotaxis has been proposed to guide sperm to egg throughout the animal
      kingdom, sperm attractants released from mammalian eggs have not been identified.
      Since the G protein subunit alpha-gustducin is accepted as a marker of
      chemosensitive cells, attempts were made to explore whether alpha-gustducin is
      also expressed in spermatozoa of mammals. Immunohistochemical approaches using an
      anti-alpha-gustducin-specific antibody revealed the most intense immunoreactivity
      in differentiating spermatids. Further evidence for the alpha-gustducin
      expression was obtained analyzing testicular and sperm-derived tissue
      preparations in western blot analyses. To elucidate whether alpha-gustducin is
      retained in mature spermatozoa, epididymal mouse and rat sperm were subjected to
      immunocytochemistry as well as immunogold electron microscopy. A specific
      staining was obtained within the circumference of the midpiece-localized
      mitochondria, on the axoneme and the outer dense fibers surrounding the
      microtubules of this region, whereas no labeling was detectable in the end piece
      regions. The analysis of ejaculated bovine and human sperm revealed a comparable
      segmental distribution pattern for alpha-gustducin. Although a possible function
      for alpha-gustducin has yet to be determined, the axonemal-associated
      localization within the midpiece and principal piece of different mammalian
      spermatozoa raises the possibility that this G protein alpha-subunit may process
      intracellular signals controlling sperm motility.

PMID- 17021832
TI  - GABA and glutamate specifically induce contractions in the sponge Tethya
      wilhelma.
AB  - Sponges (Porifera) are nerve- and muscleless. Nevertheless, they react to
      external stimuli in a coordinated way, by body contraction, oscule closure or
      stopping pumping activity. The underlying mechanisms are still unknown, but
      evidence has been found for chemical messenger-based systems. We used the sponge
      Tethya wilhelma to test the effect of gamma-aminobutyric acid (GABA) and
      glutamate (L: -Glu) on its contraction behaviour. Minimal activating
      concentrations were found to be 0.5 microM (GABA) and 50 microM (L: -Glu),
      respectively. Taking maximum relative contraction speed and minimal relative
      projected body area as a measure of the sponge's response, a comparison of the
      dose-response curves indicated a higher sensitivity of the contractile tissue for
      GABA than for L: -Glu. The concentrations eliciting the same contractile response
      differ by about 100-fold more than the entire concentration range tested. In
      addition, desensitising effects and spasm-like reactions were observed.
      Presumably, a GABA/L: -Glu metabotropic receptor-based system is involved in the
      regulation of contraction in T. wilhelma. We discuss a coordination system for
      sponges based on hypothetical chemical messenger pathways.

PMID- 17021833
TI  - Analysis of methodological deficiencies of studies reporting surgical outcome
      following cemented total-joint arthroplasty of trapezio-metacarpal joint of the
      thumb.
AB  - Cemented total-joint arthroplasty has been increasingly used in the treatment of
      end stage arthritis of the thumb trapeziometacarpal joint. Evidence supporting
      its use in the treatment of trapeziometacarpal disorders in the literature is
      very limited. Most hand surgeons agree that there are concerns about the
      methodological quality of the limited literature available. In this study, we
      analysed the methodological quality of the outcome studies on cemented total
      joint arthroplasty of the thumb. We included all the outcome studies published in
      the English literature on cemented total-joint arthroplasty of the
      trapeziometacarpal joint of thumb. We analysed these studies for methodological
      deficiencies and quality of outcome reporting based on the recommendations given
      by Coleman et al. Our study revealed that there were no uniform standards of
      outcome reporting. The mean Coleman score for the studies dealing with cemented
      total-joint arthroplasty of the thumb was 42.9. Major deficiencies were
      identified in areas like subject selection criteria (0/15), type of study
      (5.7/15), description of surgical procedure (3.7/5), description of the
      rehabilitation protocol (2/10), outcome measures (4.4/10) and outcome assessment
      (3.9/15). The methodological quality of the studies published within the last 10
      years (49.9+/-9.7) was found to be slightly better than the studies published
      over 10 years ago (39.7+/-7.8). Our study highlights the need for more evidence
      in the form of randomised controlled prospective studies conducted with good
      methodological quality, comparing the cemented total-joint arthroplasty of the
      thumb to other procedures available for the treatment of disorders of the thumb.
      Further, to improve the standards of reporting, journal editors should try to
      standardise the outcome of the reporting by following the surgical procedures on
      the thumb.

PMID- 17021834
TI  - Imaging strategies in intramuscular haemangiomas: an analysis of 20 cases.
AB  - The purpose of this study was to review the correlation between the imaging
      studies and the histological findings in the diagnosis of this disease. We
      retrospectively reviewed 21 lesions in 20 patients (median age, 23.7 years old)
      who had been diagnosed with cavernous haemangiomas (n=11), capillary (n=6), and
      mixed (n=3) types. The imaging studies were obtained with plain film radiography
      (n=20), Tc-99 m bone scans (n=5), angiography (n=7) and magnetic resonance
      imaging (MRI; n=20). All the patients underwent marginal to wide excision. Based
      on the imaging studies, the rate of accurate prediction of intramuscular
      haemangioma using MRI in our study was 90%. Using the preoperative imaging
      studies and surgical excisions, only one (5%) local recurrence happened 2 years
      after marginal excision. The remaining patients were free of disease. For the
      avoidance of recurrence, wide excision is necessary with the help of the imaging
      studies, which can provide more specific information, making possible the
      preoperative identification of characteristic features of the tumuor.

PMID- 17021835
TI  - Long term results of surgical intervention for osteoarthritis of the
      trapeziometacarpal joint : comparison of resection arthroplasty, trapeziectomy
      with tendon interposition and trapezio-metacarpal arthrodesis.
AB  - Trapeziometacarpal osteoarthritis is a common entity, often bilateral and
      predominantly affecting postmenopausal women. In the case of failure of
      conservative treatment, surgery is a good option. The aim of this study was to
      compare three surgical procedures. 63 patients (74 thumbs) with osteoarthritis of
      the trapezio-metacarpal joint were surgically treated; 54 patients were seen for
      follow-up, 7 had died and 2 were lost to follow-up. The patients were stratified
      according to treatment; resection arthroplasty (the joint surface's of the
      metacarpal and the trapezium are resected) (18 thumbs), trapeziectomy with tendon
      interposition (17 thumbs) or trapezio-metacarpal arthrodesis (28 thumbs).
      Baseline characteristics were comparable in the three groups for mean age at
      operation, Eaton classification, left right distribution and dominant hands
      operated. The average follow-up was 13 years for the resection group, 8 years for
      the trapeziectomy group and 9 years for the arthrodesis group. No statistically
      significant difference between the three groups was found for the visual analogue
      pain and satisfaction scale, pain frequency nor DASH score. Patients in the
      trapeziectomy group had significantly less pain compared to the arthrodesis group
      (p=0.025). Statistically, radial abduction was significantly better after
      trapeziectomy compared to resection arthroplasty (p<0.01) or arthrodesis
      (p=0.01). There was no difference among the three groups in grip and tip pinch
      strength nor in pain on palpation. None of the patients in the trapeziectomy
      group needed a re-operation, one patient in the resection arthroplasty group had
      a re-operation, and 22 patients in the arthrodesis group had one or more re
      operations for hardware removal or because of a complication. This study shows
      that the resection arthroplasty has equally good long term results compared to
      trapeziectomy combined with tendon interposition or arthrodesis. Resection
      arthroplasty is performed through a single incision and is technically simple. In
      our clinic resection arthroplasty is therefore the preferred technique for the
      treatment of osteoarthritis of the trapeziometacarpal joint.

PMID- 17021837
TI  - Memory processes in multiple-target visual search.
AB  - Gibson, Li, Skow, Brown, and Cooke (Psychological Science, 11, 324-327, 2000) had
      participants carry out a search task in which they were required to detect the
      presence of one or two targets. In order to successfully perform such a multiple
      target visual search task, participants had to remember the location of the first
      target while searching for the second target. In two experiments we investigated
      the cost of remembering this target location. In Experiment 1, we compared
      performance on the Gibson et al. task with performance on a more conventional
      present-absent search task. The comparison suggests a substantial performance
      cost as measured by reaction time, number of fixations and slope of the search
      functions. In Experiment 2, we looked in detail at refixations of distractors,
      which are a direct measure of attentional deployment. We demonstrated that the
      cost in this multiple-target visual search task was due to an increased number of
      refixations on previously visited distractors. Such refixations were present
      right from the start of the search. This change in search behaviour may be caused
      by the necessity of having to remember a target-allocating memory for the
      upcoming target may consume memory capacity that may otherwise be available for
      the tagging of distractors. These results support the notion of limited capacity
      memory processes in search.

PMID- 17021836
TI  - Laterally focused attention modulates asymmetric coupling in rhythmic interlimb
      coordination.
AB  - Peters (J Motor Behav 21:151-155, 1989; Interlimb coordination: neural, dynamical
      and cognitive constraints, Academic, Orlando, pp 595-615, 1994) suggested that
      expressions of handedness in bimanual coordination may be reflections of an
      inherent attentional bias. Indeed, previous results indicated that focusing
      attention on one of the limbs affected the relative phasing between the limbs in
      a manner comparable to the effects of hand dominance. The present study extended
      the comparison between the effects of attentional focus and handedness by testing
      their impact on the interactions between the limbs. Both left-handed and right
      handed participants performed rhythmic bimanual coordination tasks (in-phase and
      antiphase coordination), while directing attention to either limb. Using brief
      mechanical perturbations, the degree to which the limbs were influenced by each
      other was determined. The results revealed that the non-dominant limb was more
      strongly affected by the dominant limb than vice versa and that, in line with
      Peters' proposition, this handedness-related asymmetry in coupling strength was
      reduced when attention was focused on the non-dominant limb, thereby highlighting
      the potential relation between inherent (handedness-related) asymmetries and
      voluntary attentional asymmetries. In contrast to previous findings, the
      (commonly observed) phase lead of the dominant limb was attenuated (rather than
      accrued) when attention was focused on this limb. This unexpected result was
      explained in terms of the observed attention-related difference in amplitude
      between the limbs.

PMID- 17021838
TI  - Acute fulminant myocarditis after allogeneic peripheral blood stem cell
      transplantation with reduced-intensity conditioning for acute myelogenous
      leukemia.

PMID- 17021839
TI  - Unsuspected FDG-PET findings in the follow-up of patients with lymphoma.
AB  - 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) plays an increasing
      role in the management of patients with lymphoma, for which it is successfully
      used for staging and treatment monitoring. We report seven patients with a
      history of lymphoma who presented a positive FDG-PET suggestive of lymphoma
      relapse and for which FDG-PET oriented biopsies revealed alternative diagnoses.
      Early in lymphoma follow-up, persistence of focal increased FDG activity
      corresponded to inflammatory or infectious lesions in two patients: one
      aspergillosis and one sarcoidosis. Later in the follow-up, five cases of
      secondary malignancies were identified (three lung cancers, one epidermoid
      carcinoma, and one villous tumor) in this particularly exposed population. The
      routine use of FDG PET to evaluate lymphoma significantly increases the
      probability of detecting unexpected diseases. These cases illustrate the
      potential pitfalls in PET follow-up. Because FDG is not lymphoma-specific, a
      relapse suspected only on FDG-PET imaging requires biopsy, as alternative
      diagnoses--infectious or malignant--are possible. Our data draws clinician's
      attention to potential false-positive FDG-PET findings, which may lead to
      therapeutic mistakes. Our data also suggests that FDG-PET might be a new imaging
      modality for long-term monitoring of late effects, especially second cancer
      occurrence.

PMID- 17021840
TI  - Risk factors associated with airway allergic diseases from exposure to laboratory
      animal allergens among veterinarians.
AB  - OBJECTIVES: Investigate the risk factors for the development of occupational
      airway allergy (OAA) from exposure to laboratory animal allergens (LAA) among
      Polish veterinarians. METHODS: Two hundred veterinarians responded to the
      questionnaire and were subjected to skin prick test (SPT) to common allergens and
      LAA (rat, mouse, hamster, guinea pig, rabbit). Evaluation of total serum IgE
      level and specific IgE against occupational allergens was performed. In addition,
      bronchial hyperreactivity (BHR) and peak expiratory flow rate (PEFR) were
      measured before and after specific challenge testing (SCT) only in the subjects
      with work-related symptoms suggestive of occupational asthma (OA). RESULTS: The
      prevalence of asthmatic and ocular symptoms was statistically more prevalent in
      the group of veterinarians sensitised to LAA versus non-sensitised subjects. The
      most frequent occupational allergens of skin and serum reactivity were LAA (44.5
      and 31.5%, respectively). In 41 (20.5%) and in 22 (11%) subjects out of 200
      veterinarians, serum specific IgE to natural rubber latex (NRL) allergens and
      disinfectants was also found. Serum sensitisation to cat allergens and daily
      contact with laboratory animals (LA) increased the risk for developing isolated
      occupational rhinitis. Furthermore, working time of more than 10 years and daily
      contact with LA were also significant risk factors for the development of OAA.
      Measuring PEFR and BHR before and after SCT is a useful method to confirm the
      presence of OA. CONCLUSIONS: Allergy to LAA is an important health problem among
      veterinary medicine practitioners in Poland.

PMID- 17021841
TI  - Prevalence and host determinants of occupational bronchial asthma in animal
      shelter workers.
AB  - OBJECTIVE: We examined the risk factors for the development of airway allergy in
      animal shelter workers. METHODS: The study population comprised 88 animal shelter
      workers occupationally exposed to cats and dogs. They responded to a
      questionnaire concerning the history of exposure to animal allergens and job
      characteristics and were subjected to skin prick test (SPT) to common and
      occupational allergens (cat and dog), and determination of total serum IgE level
      and specific IgE. In addition, SPT with rat and mouse allergens were performed.
      Bronchial hyperreactivity and peak expiratory flow rate were measured at work and
      off work only in workers with work-related symptoms suggestive of occupational
      asthma (OA). RESULTS: The prevalence of OA was 9.1%. Sensitization to dog
      allergens was higher than to cats. The multivariate logistic regression analysis
      revealed a significant role of positive family history of atopy and having a dog
      as pet in the past for the development of occupational airway allergy (OR 5.9;
      95% CI 1.76, 20.00; P = 0.003; OR 6.47; 95% CI 1.90, 22.02; P = 0.002,
      respectively). In the multivariate logistic regression analysis, the risk for
      developing OA was most clearly associated with growing up in the country (OR
      7.59; 95% CI 1.25, 45.9; P = 0.025). CONCLUSIONS: Allergic disease is a serious
      occupational health concern for subjects who have occupational contact with cats
      and dogs.

PMID- 17021842
TI  - Allergy in bakers' apprentices and factors associated to non-participation in a
      cohort study of allergic sensitization.
AB  - OBJECTIVE: To describe the prevalence of atopy and respiratory symptoms among
      baker apprentices at the start of the education and factors associated with non
      participation in the study. METHODS: A total of 346 students, 22.1(0.6) years of
      age, mean (SD), from the food production programme of technical colleges in
      Denmark were invited to participate in a 3 year study. Of the students, 187
      agreed to participate and filled in a physician-administered questionnaire. The
      presence of atopy was determined by skin prick test (SPT) and serum allergen
      specific IgE (SpIgE). Bronchial hyper responsiveness to methacholine (PD(20) <or=
      1,440 microg) was determined. RESULTS: Prevalence of atopy was 32%. The
      prevalence of symptoms from the lungs and nose was 19.8 and 25.5%, respectively.
      Significantly, more SPT reactions were seen in males compared to females (39 vs.
      22%, P < 0.05). Sensitization towards flour was significantly more frequent if
      determined as SpIgE (7.3%) compared to SPT (0.5%). We found a positive
      association between atopy and lung symptoms OR 6.1 (2.8-13.2 SD) and nasal
      symptoms OR 3.7 (1.8-7.5 SD). The major reason for non-participation was fear of
      blood sampling (25.5%). CONCLUSION: The prevalence of atopy in bakers'
      apprentices was of the same magnitude in the general Danish population.
      Significantly, more male bakers' apprentices had atopy. This finding has major
      impact on the diagnostic procedures of occupational allergy in bakery workers
      emphasizing the need for standardization of the clinical tests. The main reasons
      for non-participation were, fear of blood-sampling (57%) and the 3 years
      commitment to the follow-up study (39%).

PMID- 17021843
TI  - Inhalation and dermal exposure to eight antineoplastic drugs in an industrial
      laundry facility.
AB  - OBJECTIVES: The aims of the study were to quantify levels of dermal and
      inhalation exposure to antineoplastic drugs in an industrial laundry service in
      the Netherlands and to test the removal efficiency of the washing procedure for
      removal of antineoplastic drugs. METHODS: During four workdays dermal and
      inhalation exposure to eight frequently used antineoplastic drugs
      (cyclophosphamide, ifosfamide, methotrexate, 5-fluorouracil, etoposide,
      cytarabine, gemcitabine and chlorambucil) were measured for all job titles
      involved in handling unwashed laundry. To test the removal efficiency of the
      washing procedure, 10 x 10 cm sections were excised before and after the washing
      procedure. These sections were taken from 15 bed sheets that were collected in
      hospitals of patients who were treated with one of the selected antineoplastic
      drugs. RESULTS: During none of the four measurement days, detectable levels of
      any of the eight antineoplastic drugs (cyclophosphamide, ifosfamide,
      methotrexate, 5-fluorouracil, etoposide, cytarabine, gemcitabine, or
      chlorambucil) were found on workers' skin of hands or in any of the air samples.
      Only four out of the 15 bed sheets from patients that were treated with
      antineoplastic drugs appeared to be contaminated with detectable levels of
      antineoplastic drugs before the washing procedure (range 13.0-3,060 ng/100
      cm(2)). After the pre-washing and after the complete washing procedure, no
      detectable levels of any of the eight antineoplastic drugs were found anymore in
      the selected bed sheets. CONCLUSIONS: The implementation of guidelines for
      working with antineoplastic drugs seems to be successful in reducing exposure to
      antineoplastic drugs of workers in this laundry facility to an acceptable, non
      detectable level and to remove antineoplastic drug contamination from bed linen.

PMID- 17021844
TI  - Effects of mercury vapor exposure on neuromotor function in Chinese miners and
      smelters.
AB  - OBJECTIVES: Current risk assessment of elemental mercury vapor is based on the
      tremor toxicity. To clarify the neuromotor effects of occupational exposure to
      mercury vapor, hand tremor and postural sway were measured in 27 miners and
      smelters (i.e., exposed workers) and 52 unexposed subjects. METHODS: Urine
      samples were collected and total mercury and creatinine concentrations were
      determined. Data of the tremor and postural sway were analyzed using the fast
      Fourier transformation. RESULTS: The geometric means of the urinary mercury level
      (UHg) were 228 (range 22.6-4,577) microg/g creatinine for the exposed workers and
      2.6 (1.0-17.4) microg/g creatinine for the unexposed subjects. Total tremor
      intensity and frequency-specific tremor intensities at 1-6 and 10-14 Hz were
      significantly larger in the exposed workers than in the unexposed subjects (P <
      0.05), but they were not significantly related to the UHg among the exposed
      workers (P > 0.05). In contrast, there were no significant differences in any
      postural sway parameters between the above two groups (P > 0.05), but the
      transversal sway with eyes open was positively related to the UHg among the
      exposed workers in using multiple regression analysis (P < 0.05). CONCLUSIONS:
      These findings suggest that postural sway, as well as hand tremor, may be
      affected by elemental mercury vapor exposure, but the former test seems to be
      less sensitive to mercury than the latter one.

PMID- 17021845
TI  - Occupational respiratory health of New Zealand horse trainers.
AB  - OBJECTIVES: To confirm that working with horses is an occupational respiratory
      hazard and observed associations are not attributable to confounding. METHODS: A
      postal survey of the respiratory health of 659 horse trainers and a comparison
      group of 506 vegetable growers was conducted. Data were analysed using logistic
      regression. RESULTS: Relative to vegetable growers, horse trainers reported
      higher rates of chronic bronchitis [odds ratio (OR) = 6.8, 95% confidence
      interval (CI): 2.2-21.4] and organic dust toxic syndrome/farmers' lung (ODTS/FL)
      (OR = 3.5, 95% CI: 1.8-6.8). Grinding oats, spreading hay, and using powdered
      feed supplements were associated with increased respiratory symptoms among
      trainers. Associations between symptoms and working with horses increased for
      full-time workers. CONCLUSIONS: This study found evidence that working with
      horses is a risk factor for ODTS/FL and bronchitis. The associations did not
      appear to be explained by bias, including confounding. However, the possibility
      of confounding cannot be entirely ruled out, and confirmatory studies are needed.
      Future studies should consider inorganic dust exposures.

PMID- 17021846
TI  - Modeling the euglycemic hyperinsulinemic clamp by stochastic differential
      equations.
AB  - The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental
      procedure for the determination of insulin sensitivity. In the present study, 16
      subjects with BMI between 18.5 and 63.6 kg/m(2) have been studied with a long
      duration (5 hours) EHC. In order to explain the oscillations of glycemia
      occurring in response to the hyperinsulinization and to the continuous glucose
      infusion at varying speeds, we first hypothesized a system of ordinary
      differential equations (ODEs), with limited success. We then extended the model
      and represented the experiment using a system of stochastic differential
      equations (SDEs). The latter allow for distinction between (i) random variation
      imputable to observation error and (ii) system noise (intrinsic variability of
      the metabolic system), due to a variety of influences which change over time. The
      stochastic model of the EHC was fitted to data and the system noise was estimated
      by means of a (simulated) maximum likelihood procedure, for a series of different
      hypothetical measurement error values. We showed that, for the whole range of
      reasonable measurement error values: (i) the system noise estimates are non
      negligible; and (ii) these estimates are robust to changes in the likely value of
      the measurement error. Explicit expression of system noise is physiologically
      relevant in this case, since glucose uptake rate is known to be affected by a
      host of additive influences, usually neglected when modeling metabolism. While in
      some of the studied subjects system noise appeared to only marginally affect the
      dynamics, in others the system appeared to be driven more by the erratic
      oscillations in tissue glucose transport rather than by the overall glucose
      insulin control system. It is possible that the quantitative relevance of the
      unexpressed effects (system noise) should be considered in other physiological
      situations, represented so far only with deterministic models.

PMID- 17021847
TI  - Successful genetic transformation of Chinese cabbage using phosphomannose
      isomerase as a selection marker.
AB  - A mannose selection system was adapted for use in the Agrobacterium-mediated
      transformation of Chinese cabbage. This system makes use of the pmi gene that
      encodes phosphomannose isomerase, which converts mannose-6-phosphate to fructose
      6-phosphate. Hypocotyl explants from 4-5-day-old seedlings of Chinese cabbage
      inbred lines were pre-cultured for 2-3 days and then infected with Agrobacterium.
      Two genes (L: -guluno-gamma-lactone oxidase, GLOase, and jasmonic methyl
      transferase, JMT) were transformed into Chinese cabbage using the transformation
      procedure developed in this study. We found that supplementing the media with 7 g
      l(-1) mannose and 2% sucrose provides the necessary conditions for the selection
      of transformed plants from nontransformed plants. The transformation rates were
      1.4% for GLOase and 3.0% for JMT, respectively. The Southern blot analysis
      revealed that several independent transformants (T (0)) were obtained from each
      transgene. Three different inbred lines were transformed, and most of the T (1)
      plants had normal phenotypes. The transformation method presented here for
      Chinese cabbage using mannose selection is efficient and reproducible, and it can
      be useful to introduce a desirable gene(s) into commercially useful inbred lines
      of Chinese cabbage.

PMID- 17021848
TI  - Ultrasonic treatment stimulates multiple shoot regeneration and explant
      enlargement in recalcitrant squash cotyledon explants in vitro.
AB  - Ultrasonic treatment (0.5-2 min) stimulated multiple shoot regeneration to high
      levels in vitro from recalcitrant cotyledon explants of commercial squash
      (Cucurbita pepo L.) cultivars Ma'yan and Bareqet, on Murashige and Skoog [Physiol
      Plant 15:473-497, 1962] (regeneration) medium augmented with 4.4 microM
      benzyladenine. At this stage, unsonicated control explants regenerated only a few
      very small shoots or bud-like structures. Ultrasound also stimulated massive
      explant growth. Ultrasound treatment resulted in further multiple shoot
      production (five times greater than control) after explant transfer to elongation
      medium (Murashige and Skoog [Physiol Plant 15:473-497, 1962] medium with 0.44
      microM benzyladenine and 2.9 microM gibberellic acid). Longer ultrasonic
      treatments (5 or 10 min) promoted multiple shoot regeneration and explant growth
      accompanied by hyperhydration. Scanning electron microscope observations showed
      that 2 min ultrasound changed the joint area between epidermal cells and removed
      some of the surface from the cotyledon epidermal cells, without gross surface
      injury to the explants. Longer periods of ultrasound (5-10 min) caused further
      surface erosion. Rubbing the explant contact surface with chloroform or sandpaper
      emulated the effect of sonication on shoot regeneration and explant growth,
      demonstrating that ultrasound exerts its morphogenic influence by surface
      removal. Sonication of explants from other batches of squash seeds (of cultivars
      Ma'yan and True French), that regenerated without such treatment, reduced
      regeneration and caused hyperhydration. This is the first report of stimulation
      of in vitro regeneration by ultrasound treatment.

PMID- 17021849
TI  - Regulation of the beta-hydroxyacyl ACP dehydratase gene of Picea mariana by
      alternative splicing.
AB  - The gene for beta-hydroxyacyl ACP dehydratase, a de novo fatty acid biosynthetic
      enzyme, was cloned from Picea mariana (black spruce) and consists of five exons
      and four introns. The first intron of the beta-hydroxyacyl ACP dehydratase mRNA
      is alternatively spliced. Retention of intron 1 in splice variants results in
      truncation of the beta-hydroxyacyl ACP dehydratase ORF at a premature termination
      codon. In addition, splicing of intron 1 was found to be associated with cold
      temperature. mRNAs retaining intron 1 increase with seed imbibition at 22 degrees
      C but not 4 degrees C, whereas, splicing of intron 1 increases in winter weeks
      with temperatures below freezing. These results provide evidence that alternative
      splicing may also contribute to regulation of lipid biosynthesis in Picea
      mariana.

PMID- 17021850
TI  - Incomplete sister chromatid separation of long chromosome arms.
AB  - Chromosome segregation ensures the equal partitioning of chromosomes at mitosis.
      However, long chromosome arms may pose a problem for complete sister chromatid
      separation. In this paper we report on the analysis of cell division in primary
      cells from field vole Microtus agrestis, a species with 52 chromosomes including
      two giant sex chromosomes. Dual chromosome painting with probes specific for the
      X and the Y chromosomes showed that these long chromosomes are prone to mis
      segregate, producing DNA bridges between daughter nuclei and micronuclei.
      Analysis of mitotic cells with incomplete chromatid separation showed that
      reassembly of the nuclear membrane, deposition of INner CENtromere Protein
      (INCENP)/Aurora B to the spindle midzone and furrow formation occur while the two
      groups of daughter chromosomes are still connected by sex chromosome arms. Late
      cytokinetic processes are not efficiently inhibited by the incomplete segregation
      as in a significant number of cell divisions cytoplasmic abscission proceeds
      while Aurora B is at the midbody. Live-cell imaging during late mitotic stages
      also revealed abnormal cell division with persistent sister chromatid
      connections. We conclude that late mitotic regulatory events do not monitor
      incomplete sister chromatid separation of the large X and Y chromosomes of
      Microtus agrestis, leading to defective segregation of these chromosomes. These
      findings suggest a limit in chromosome arm length for efficient chromosome
      transmission through mitosis.

PMID- 17021851
TI  - Dactylorhin B reduces toxic effects of beta-amyloid fragment (25-35) on neuron
      cells and isolated rat brain mitochondria.
AB  - beta-amyloid is strongly implicated in Alzheimer's pathology, and mitochondria
      play an important role in neurodegenerative disorders. Dactylorhin B [short for
      bis(4-beta-D-glucopyranosyloxybenzyl)-2-beta-D-glucopyranosyl-2-isobutyltartrate
      (DHB)] is an active compound isolated from Coeloglossum viride. (L.) Hartm. var.
      bracteatum (Willd.) and may have neuroprotective effects. In the present study,
      we investigated the damage of rat brain mitochondrial function induced by beta
      amyloid and the protective effect of DHB. Isolated rat brain mitochondria were
      incubated with amyloid-beta peptide (Abeta)(25-35) alone or together with DHB.
      reactive oxygen species production, pyruvate dehydrogenase complex activity,
      alpha-ketoglutarate dehydrogenase complex activity, cytochrome c oxidase
      activity, mitochondrial swelling, mitochondrial membrane potential and the
      release of cytochrome c from mitochondria were measured. Data showed that
      Abeta(25-35) directly disrupted mitochondrial function, inhibited the key enzymes
      and contributed to apoptosis and the deficiency of energy metabolism. Co
      incubation of DHB attenuated Abeta(25-35)-induced pathological changes. The
      significance of DHB in the management of mitochondria-related disorders is
      discussed.

PMID- 17021852
TI  - Calcineurin and Erk1/2-signaling pathways are involved in the antiapoptotic
      effect of cyclosporin A on astrocytes exposed to simulated ischemia in vitro.
AB  - The present study focused on mechanisms involved in the anti-apoptotic effect of
      cyclosporin A (CsA) towards ischemic injured astrocytes in vitro [under combined
      oxygen glucose deprivation (OGD)]. We investigated whether this action might be
      mediated through activation of extracellular signal regulated kinases 1 and 2
      (Erk1/2) or attenuation of calcineurin (CaN) by immunosuppressant in ischemic
      astrocytes. Additionally, the influence of CsA on phosphorylation of Akt kinase
      was determined. After 21 days of in vitro culture, astrocytes were subjected to
      OGD (for 8 h) and CsA (0.25-10 microM); 0.25 microM CsA distinctly stimulated the
      Erk1/2 pathway in astrocytes exposed to OGD. This protective effect of CsA was
      strongly associated with CaN inhibition, increased expression of anti-apoptotic
      factors such as Bcl-X(L) and NF-kappaB, as well as suppression of caspase-3
      activity. Maximum p-Akt kinase expression was observed following treatment with 1
      microM CsA. Finally, we also demonstrated that the beneficial effect of CsA at a
      concentration of 10 microM is related mainly to strong CaN inhibition. The
      results obtained suggest that, depending on the concentration used, CsA might act
      as a protective agent towards ischemia-injured astroglial cells through
      alternative intracellular pathways associated with increased p-Erk1/2 and p-Akt
      expression or CaN inactivation.

PMID- 17021853
TI  - Treatment of the overactive bladder syndrome with muscarinic receptor
      antagonists: a matter of metabolites?
AB  - Antagonists of muscarinic acetylcholine receptors, such as darifenacin,
      oxybutynin, propiverine, solifenacin, tolterodine, and trospium, are the mainstay
      of the treatment of the overactive bladder syndrome. Fesoterodine is a newer drug
      awaiting regulatory approval. We briefly review the pharmacological activity of
      their metabolites and discuss how active metabolites may contribute to their
      efficacy and tolerability in vivo. Except for trospium, and perhaps solifenacin,
      all of the above drugs form active metabolites, and their presence and activity
      need to be taken into consideration when elucidating relationships between
      pharmacokinetics and pharmacodynamics of these drugs. Moreover, the ratios
      between parent compounds and metabolites may differ depending on genotype of the
      metabolizing enzymes, concomitant medication, and/or drug formulation.
      Differential generation of active metabolites of darifenacin or tolterodine are
      unlikely to influence the overall clinical profile of these drugs in a major way
      because the active metabolites exhibit a similar pharmacological profile as the
      parent compound. In contrast, metabolites of oxybutynin and propiverine may
      behave quantitatively or even qualitatively differently from their parent
      compounds and this may have an impact on the overall clinical profile of these
      drugs. We conclude that more comprehensive studies of drug metabolites are
      required for an improved understanding of their clinical effects.

PMID- 17021855
TI  - Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement
      in patients with advanced colorectal cancer. Effects on nutritional and
      inflammatory status: a phase II trial.
AB  - GOALS: The aim of the study was to assess the impact of an eicosapentanoic acid
      containing protein and energy dense oral nutritional supplement (EPA-ONS) on
      nutritional and inflammatory status, quality of life (QOL), plasma phospholipids
      (PPL) and cytokine profile, tolerance of irinotecan-containing chemotherapy and
      EPA-ONS in patients with advanced colorectal cancer (CRC) receiving chemotherapy.
      MATERIALS AND METHODS: Patients with advanced CRC having one prior chemotherapy
      regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing
      chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and
      continued for 3 cycles of treatment (9 weeks). All assessments including weight,
      body composition, C-reactive protein (CRP), QOL, dietary intake, PPL and cytokine
      analyses were performed at baseline, 3 and 9 weeks. RESULTS: Twenty-three
      patients were enrolled, 20 completed 3 weeks, and 15 completed 9 weeks. The mean
      EPA-ONS intake was 1.7 tetrapaks (408 ml) daily. There was a significant increase
      in mean weight (2.5 kg) at 3 weeks (p=0.03). Lean body mass (LBM) was maintained.
      Protein and energy intake significantly decreased after the commencement of
      chemotherapy (protein p=0.003, energy p=0.02). There was a significant increase
      in energy levels (p=0.03), whilst all other QOL measures were maintained. PPL EPA
      levels increased significantly over the first 3 weeks. Mean CRP increased by 14.9
      mg/L over the first 3 weeks (p=0.004), but decreased to baseline levels by the
      end of the trial. There was a significant correlation between plasma IL-6 and IL
      10 concentrations and survival, and between IL-12 and toxicity. CONCLUSION:
      Dietary counseling and the provision of EPA-ONS may result in maintenance of
      nutritional status and QOL, however randomized trials are required to evaluate
      the impact of EPA on toxicity from chemotherapy.

PMID- 17021856
TI  - Factors associated with place of death of cancer patients in the Mexico City
      Metropolitan area.
AB  - OBJECTIVE: To improve the care of cancer patients by understanding the factors
      associated with the place of death. PATIENTS AND METHODS: We conducted a
      retrospective study of death certificates registered in Mexico during 2003. Adult
      cases were included if the underlying cause of death was cancer, death location
      was in the Mexico City Metropolitan Area (MCMA), and information was available on
      sociodemographic characteristics and place of death (home or medical unit). MAIN
      RESULTS: Of the 10,561 cases meeting the inclusion criteria, 54% died at home.
      More women (55%) than men died of cancer and at a younger age (63 vs 64 years,
      respectively; p<0.001). Multivariate analysis indicated that patients diagnosed
      with leukemia and lymphoma were 3.6 times more likely to die in hospitals than
      patients diagnosed with other cancers (p<0.001). Compared with patients who died
      at home, patients who died in hospitals were significantly more educated,
      younger, and residents of counties with more hospital beds density (p<0.001,
      p<0.001, and p=0.003, respectively). Certificates for in-hospital deaths were
      more likely to be signed by other physician or health professional than were
      those for at-home deaths (p<0.001). Cases with usual residency located outside
      the study area were 27 times more likely to die in hospitals than were
      metropolitan-area residents (p<0.001). CONCLUSIONS: Patients dying at home tended
      to be of older age, less educated, diagnosed with prostate, urinary tract or
      gastrointestinal cancers, and residents of the MCMA. Health planners should
      consider determinants of place of death when allocating hospital or home-based
      palliative care units.

PMID- 17021857
TI  - Factors related to posttraumatic stress in adolescent survivors of childhood
      cancer and their parents.
AB  - GOALS OF WORK: The purpose of this study was to investigate factors related to
      severe posttraumatic stress symptoms (PTSS) in adolescent survivors of childhood
      cancer and their parents. MATERIALS AND METHODS: Eighty-nine families (88
      adolescent survivors of childhood cancer, 87 mothers, 72 fathers) completed a
      self-report questionnaire. Multivariate logistic regression analyses were
      performed using the following risk factors for severe PTSS: trait anxiety, family
      functioning, demographic and medical variables. MAIN RESULTS: Severe PTSS were
      reported by 10.9% (n=9) of the survivors, 20.7% (n=18) of the mothers, and 22.2%
      (n=16) of the fathers. Preliminary analyses found significant correlations of
      PTSS between mother-survivor (Spearman's gamma=0.377, p<0.01) and mother-father
      (Spearman's gamma=0.483, p<0.01). The results of multivariate analyses indicated
      that higher trait anxiety [odds ratio (OR):1.16; 95% confidence interval (CI):
      1.03-1.31; p<0.05] and having medical sequelae (OR: 5.85; 95% CI:1.02-33.72;
      p<0.05) were significant factors related to PTSS for survivors. For mothers, the
      significant PTSS-related factors were: higher trait anxiety (OR:1.13; 95% CI:1.04
      1.23; p<0.01); 5- to 9-year interval from the first diagnosis to the present
      investigation, compared to more than a 10-year interval (OR: 6.45; 95% CI:1.67
      24.89; p<0.01); and a relatively lower rating on "roles" of family functioning
      (OR: 12.34; 95% CI:1.11-136.97; p<0.05). For fathers, trait anxiety was a
      significant related factor (OR: 1.07; 95% CI:1.01-1.14; p<0.05). CONCLUSIONS:
      Survivors and their parents suffered from PTSS after long interval from
      completion of treatment, and PTSS-related factors varied for each family member.
      Appropriate allocation of responsibility for family functioning may promote the
      ability to decrease PTSS, especially for mothers.

PMID- 17021858
TI  - Aberrant expression of HLA-B*3565Q is associated with a disrupted disulfide bond.
AB  - The identification of expression variants is a challenge in HLA diagnostics. We
      here describe the identification of the novel allele HLA-B*3565Q. The serological
      HLA class I type, as determined by a lymphocytotoxicity test, was A11,24; B38;
      Bw4; Cw-; whereas PCR-sequence-specific primers resulted in A*11,*24, B*35,*38;
      Cw*12, thus suggesting the presence of a nonexpressed B*35 allele. To clarify the
      lack of serological HLA-B35 reactivity, exons 2 and 3 were sequenced following
      haplotype-specific amplification. At position 564 from the beginning of the
      coding region (exon 3), a transversion (C-->G) was observed, which, at the amino
      acid level, results in a substitution from cysteine to tryptophane at position
      164 of the mature polypeptide. Because this position is essential for the
      formation of a disulfide bond linking the cysteine residues at positions 101 and
      164, which is strongly conserved in functional class I molecules of vertebrates,
      the disruption of this bond is very likely to be the reason for the lack of
      serological detectability. We later found the same novel allele in a second
      unrelated individual, of whom we were able to establish a lymphoblastoid cell
      line (B-LCL). Serological testing of this B-LCL indicated a very low aberrant
      expression of HLA-B*3565Q, which cannot be expected to be detected by standard
      serology techniques.

PMID- 17021859
TI  - Molecular study of Mhc-DRB in wild chacma baboons reveals high variability and
      evidence for trans-species inheritance.
AB  - The MHC class II genes of many primate species were investigated extensively in
      recent years. However, while Mhc-DRB genes were studied in Old World monkeys such
      as rhesus macaques, the Mhc-DRB of baboons was only studied in a limited way.
      Because of their close anatomical and physiological relationship to humans,
      baboons are often used as models for reproduction and transplantation research.
      Baboons are also studied as a model species in behavioural ecology. Thus,
      identification of MHC genes would provide a foundation for studies of Mhc,
      biology and behaviour. Here, we describe the use of PCR, cloning, denaturing
      gradient gel electrophoresis (DGGE) and sequencing to identify Mhc-DRB sequences
      in wild chacma baboons (Papio ursinus). We amplified the highly variable second
      exon of baboon Mhc-DRB sequences using generic DRB primers. To validate and
      optimize the DGGE protocol, four DNA samples were initially studied using cloning
      and sequencing. Clones were screened using a novel RFLP approach to increase the
      number of clones identified for each individual. Results from cloning and
      sequencing were used to optimise DGGE conditions for Mhc-DRB genotyping of the
      remaining study subjects. Using these techniques, we identified 16 Paur-DRB
      sequences from 30 chacma baboons. On the basis of phylogenetic tree analyses,
      representatives of the Mhc-DRB1 and Mhc-DRB5 loci, and 13 different DRB lineages
      were identified. Evidence for trans-species inheritance of some Mhc-DRB sequences
      comes from high identity between the new Paur-DRB sequences and sequences from
      Papio cynocephalus, Macaca mulatta and possibly Galago moholi.

PMID- 17021860
TI  - Reassignment of the murine 3'TRDD1 recombination signal sequence.
AB  - T cell receptor genes are assembled in developing T lymphocytes from discrete V,
      D, and J genes by a site-specific somatic rearrangement mechanism. A flanking
      recombination signal, composed of a conserved heptamer and a semiconserved
      nonamer separated by 12 or 23 variable nucleotides, targets the activity of the
      rearrangement machinery to the adjoining V, D, and J genes. Following the
      rearrangement of V, D, or J genes, their respective recombination signals are
      ligated together. Although these signal joints are allegedly invariant, created
      by the head-to-head abuttal of the heptamers, some do exhibit junctional
      diversity. Recombination signals were initially identified by comparison and
      alignment of germ-line sequences with the sequence of rearranged genes. However,
      their overall low level of sequence conservation makes their characterization
      solely from sequence data difficult. Recently, computational analysis unraveled
      correlations between nucleotides at several positions scattered within the spacer
      and recombination activity, so that it is now possible to identify putative
      recombination signals and determine and predict their recombination efficiency.
      In this paper, we analyzed the variability introduced in signal joints generated
      after rearrangement of the TRDD1 and TRDD2 genes in murine thymocytes. The
      recurrent presence of identical nucleotides inserted in these signal joints led
      us to reconsider the location and sequence of the TRDD1 recombination signal. By
      combining molecular characterization and computational analysis, we show that the
      functional TRDD1 recombination signal is shifted inside the putative coding
      sequence of the TRDD1 gene and, consequently, that this gene is shorter than
      indicated in the databases.

PMID- 17021861
TI  - IL-1 Receptor antagonist as a positional candidate gene in a murine model of
      allergic asthma.
AB  - Interleukin-1 receptor antagonist (IL-1ra) is an inhibitor of the proinflammatory
      IL-1. The IL-1ra gene (Il1rn) maps near the allergen-induced bronchial hyper
      responsiveness-1 locus, Abhr1, which we previously mapped to murine chromosome 2
      using A/J (asthma susceptible) and C3H/HeJ (asthma resistant) mice. We evaluated
      the role of Il1rn in our mouse model by comparing its genomic sequence between
      A/J and C3H/HeJ mice as well as assessing strain-specific RNA and protein
      production in response to allergen. We identified no functional sequence
      variations in the Il1rn gene between A/J and C3H/HeJ mice. Il1rn mRNA and protein
      were induced by ovalbumin (OVA) exposure in both strains, but to a greater extent
      in A/J mice at the earlier time points. We examined other IL-1 family members
      (Il1a, Il1b, Il1f9, and Il1r2) and found OVA-induced expression increases at 6 h,
      yet only Il1b and Il1f9 had strain-specific differences. Of these, only Il1f9 is
      located within Abhr1, and we found several non-coding polymorphisms in the Il1f9
      gene between A/J and C3H/HeJ mice. Our results exclude Il1rn as the gene for
      Abhr1 and indicate that Il1f9 warrants further investigation based on genetic and
      expression differences observed in our mouse model of allergic asthma.

PMID- 17021862
TI  - Sequence variant in the laminin gamma1 (LAMC1) gene associated with familial
      pelvic organ prolapse.
AB  - Pelvic organ prolapse is a common condition, affecting up to a third of women
      throughout their lifetime. Genetic factors are believed to account for about 30%
      of the incidence, and are the least understood component of the disorder.
      Familial cases, particularly those in which prolapse manifests in young women,
      are especially valuable in the effort to find the genes involved. We recently
      reported autosomal dominant transmission as the most likely mode of inheritance,
      based on a collection of families with high incidence of prolapse. Of greatest
      interest was a family in which three generations of female relatives suffered
      from prolapse at a very young age. A genome-wide linkage scan performed using the
      Affymetrix GeneChip Human mapping 10K array identified ten regions with a LOD
      score of 1.5, the maximum possible for this family. Candidate genes within those
      regions were analyzed for expression in vaginal tissue by RT-PCR. Of the genes
      confirmed to be expressed, LAMC1 was further evaluated by sequencing and select
      single nucleotide polymorphism (SNP) genotyping for causative sequence variants
      in affected family members. We identified one such SNP, rs10911193. The rare T
      variant segregating with the condition is present at a frequency of 4.9% in the
      general population and 22% among probands from our cohort of families. It affects
      the binding site for NFIL3, a transcription factor that we verified to be co
      expressed in vaginal tissue. Altogether these data suggest that a polymorphism in
      the promoter of LAMC1 may increase the susceptibility to early-onset pelvic organ
      prolapse.

PMID- 17021863
TI  - The Macrostomum lignano EST database as a molecular resource for studying
      platyhelminth development and phylogeny.
AB  - We report the development of an Expressed Sequence Tag (EST) resource for the
      flatworm Macrostomum lignano. This taxon is of interest due to its basal
      placement within the flatworms. As such, it provides a useful comparative model
      for understanding the development of neural and sensory organization. It was
      anticipated on the basis of previous studies [e.g., Sanchez-Alvarado et al.,
      Development, 129:5659-5665, (2002)] that a wide range of developmental markers
      would be expressed in later-stage macrostomids, and this proved to be the case,
      permitting recovery of a range of gene sequences important in development. To
      this end, an adult Macrostomum cDNA library was generated and 7,680 Macrostomum
      ESTs were sequenced from the 5' end. In addition, 1,536 of these aforementioned
      sequences were sequenced from the 3' end. Of the roughly 5,416 non-redundant
      sequences identified, 68% are similar to previously reported genes of known
      function. In addition, nearly 100 specific clones were obtained with potential
      neural and sensory function. From these data, an annotated searchable database of
      the Macrostomum EST collection has been made available on the web. A major
      objective was to obtain genes that would allow reconstruction of embryogenesis,
      and in particular neurogenesis, in a basal platyhelminth. The sequences recovered
      will serve as probes with which the origin and morphogenesis of lineages and
      tissues can be followed. To this end, we demonstrate a protocol for combined
      immunohistochemistry and in situ hybridization labeling in juvenile Macrostomum,
      employing homologs of lin11/lim1 and six3/optix. Expression of these genes is
      shown in the context of the neuropile/muscle system.

PMID- 17021864
TI  - PDZ-domain-binding sites are common among cadherins.
AB  - Cadherins are Ca(2+)-dependent cell adhesion molecules that play fundamental
      roles in animal development and homeostasis. A number of cadherins contain
      conserved binding sites for catenins in their cytoplasmic region that are
      important for the adhesive function of these cadherins by mediating their
      interaction to the cytoskeleton. However, most cadherins lack apparent binding
      sites for catenins and their cytoplasmic interacting partners are mostly unknown.
      In this paper, we show, using bioinformatics, that a number of insect and
      vertebrate cadherins lacking catenin-binding sites contain conserved consensus
      sequences for C-terminal PSD-95/Discs-large/ZO-1 (PDZ)-domain-binding sites. This
      suggests that PDZ-domain-containing proteins are common cytoplasmic interacting
      partners for cadherins lacking catenin-binding sites.

PMID- 17021865
TI  - Embryological ontogeny of aromatase gene expression in Chrysemys picta and
      Apalone mutica turtles: comparative patterns within and across temperature
      dependent and genotypic sex-determining mechanisms.
AB  - Although the role of aromatase in many estrogen-dependent reproductive and
      metabolic functions is well documented in vertebrates, its involvement in the
      ovarian development of species exhibiting temperature-dependent sex determination
      (TSD) is incompletely understood. This is partly due to the conflicting temporal
      and spatial pattern of aromatase expression and activity across taxa. To help
      resolve this ongoing debate, we compared for the first time the embryological
      ontogeny of aromatase expression in turtles possessing genotypic sex
      determination (GSD) (Apalone mutica) and TSD (Chrysemys picta) incubated under
      identical conditions. As anticipated, we found no significant thermal differences
      in aromatase expression at any stage examined (prior to until the end of the
      thermosensitive period) in A. mutica. Surprisingly, the same was true for C.
      picta. When placed in a phylogenetic context, our results suggest that aromatase
      expression is evolutionarily plastic with respect to sex determination in
      reptiles, and that differences between reptilian TSD and GSD are not aromatase
      driven. Further research across TSD and GSD species is warranted to fully
      decipher the evolution of functional differences among sex-determining
      mechanisms.

PMID- 17021866
TI  - Polarised expression of FoxB and FoxQ2 genes during development of the hydrozoan
      Clytia hemisphaerica.
AB  - We have characterised the expression of four genes coding for Forkhead box
      containing ('Fox') transcription factors identified from the hydrozoan
      (Leptomedusa) Clytia hemisphaerica. Phylogenetic analyses including all available
      non-bilaterian Fox sequences placed these genes in subfamilies B, Q2 (two genes)
      and O, and indicated that at least 17 Fox subfamilies were present in the common
      cnidarian/bilaterian ancestor, with multiple subsequent losses in cnidarian
      lineages. Chordate FoxB and FoxQ2A subfamily genes show polarised expression in
      early embryos. Correspondingly, Clytia CheFoxB expression was localised around
      the gastrulation site (future oral pole) at blastula and gastrula stages, with
      CheFoxQ2a expressed in a complementary aboral domain, maintained through larval
      development. Distinct later expression domains were observed for CheFoxB in the
      larval endoderm region, and in the statocyst, gonad and tentacle bulb of the
      medusa. A second Clytia FoxQ2 gene, CheFoxQ2b, not expressed in the embryo, larva
      or polyp, was detected uniquely in the gonads of the medusa. In contrast,
      CheFoxO, whose sequence indicates regulation by the PI3-Kinase/PKB signalling
      pathway consistent with known roles in bilaterian developmental regulation, was
      detected throughout the Clytia life cycle. CheFoxO expression was enhanced in
      regions associated with growth control including larval poles, gonad and the
      margin of the medusa bell. These results support the idea that an early embryonic
      patterning system involving FoxB and FoxQ2 family genes has been evolutionary
      conserved and indicate that Fox family genes have also acquired distinct roles
      during other phases of the hydrozoan life cycle.

PMID- 17021867
TI  - Is the prevalence of Stenotrophomonas maltophilia isolation and nosocomial
      infection increasing in intensive care units?
AB  - The study presented here was conducted over a period of 4 years (2001-2004) to
      investigate changes in the number of S. maltophilia isolates detected per 1,000
      patient days and to look at the incidence density of nosocomial infections caused
      by S. maltophilia. The analysis was based on data provided by 34 German intensive
      care units participating continuously in the national project "Surveillance of
      Antimicrobial Use and Resistance in ICUs"; 31 of these ICUs reported nosocomial
      infections to the German infection surveillance system, KISS, during the study
      period.

PMID- 17021869
TI  - Toxicogenomic analysis of sodium hypochlorite antimicrobial mechanisms in
      Pseudomonas aeruginosa.
AB  - Sodium hypochlorite (bleach) is routinely used in hospitals and health care
      facilities for surface sterilization; however, the mechanism of action by which
      this disinfectant kills and the extent to which Pseudomonas aeruginosa is
      resistant to sodium hypochlorite have not been elucidated. Consequently,
      nosocomial infections from P. aeruginosa result in considerable casualties and
      economic hardship. We report the genome-wide transcriptome response of P.
      aeruginosa to sodium hypochlorite-induced oxidative stress via the use of DNA
      microarrays. In addition to a general oxidative stress response, our data
      revealed a downregulation of virtually all genes related to oxidative
      phosphorylation and electron transport and an upregulation of many organic sulfur
      transport and metabolism genes.

PMID- 17021868
TI  - Effect of fermentation temperature on hydrogen production from cow waste slurry
      by using anaerobic microflora within the slurry.
AB  - We examined hydrogen production from a dairy cow waste slurry (13.4 g of volatile
      solids per liter) by batch cultures in a temperature range from 37 to 85 degrees
      C, using microflora naturally present within the slurry. Without the addition of
      seed bacteria, hydrogen was produced by simply incubating the slurry, using the
      microflora within the slurry. Interestingly, two peaks of fermentation
      temperatures for hydrogen production from the slurry were observed at 60 and 75
      degrees C (392 and 248 ml H2 per liter of slurry, respectively). After the
      termination of the hydrogen evolution, the microflora cultured at 60 degrees C
      displayed hydrogen-consuming activity, but hydrogen-consuming activity of the
      microflora cultured at 75 degrees C was not detected, at least for 24 days. At
      both 60 and 75 degrees C, the main by-product was acetate, and the optimum pH of
      the slurry for hydrogen production was around neutral. Bacteria related to
      hydrogen-producing moderate and extreme thermophiles, Clostridium thermocellum
      and Caldanaerobacter subterraneus, were detected in the slurries cultured at 60
      and 75 degrees C, respectively, by denaturing gradient gel electrophoresis
      analyses, using the V3 region of 16S rDNA.

PMID- 17021870
TI  - Microbial transformation of benzene to cis-3,5-cyclohexadien-1,2-diols by
      recombinant bacteria harboring toluene dioxygenase gene tod.
AB  - Toluene dioxygenase (TDO) catalyzes asymmetric cis-dihydroxylation of aromatic
      compounds. To achieve high efficient biotransformation of benzene to benzene cis
      diols, Pseudomonas putida KT2442, Pseudomonas stutzeri 1317, and Aeromonas
      hydrophila 4AK4 were used as hosts to express TDO gene tod. Plasmid pSPM01, a
      derivative of broad-host plasmid pBBR1MCS-2 harboring tod from plasmid pKST11,
      was constructed and introduced into the above three strains. Their abilities to
      catalyze the biotransformation of benzene to benzene cis-diols, namely, cis-3,5
      cyclohexadien-1,2-diols abbreviated as DHCD, were examined. In shake-flask
      cultivation under optimized culture media and growth condition, benzene cis-diols
      production by recombinant P. putida KT2442 (pSPM01), P. stutzeri 1317 (pSPM01),
      and A. hydrophila 4AK4 (pSPM01) were 2.68, 2.13, and 1.17 g/l, respectively. In
      comparison, Escherichia coli JM109 (pSPM01) and E. coli JM109 (pKST11) produced
      0.45 and 0.53 g/l of DHCD, respectively. When biotransformation was run in a 6-l
      fermenter, DHCD production in P. putida KT2442 (pSPM01) was approximately 60 g/l;
      this is the highest DHCD production yield reported so far.

PMID- 17021871
TI  - Adsorption of bisphenol A by lactic acid bacteria, Lactococcus, strains.
AB  - Ten strains of the genus Lactococcus were examined for their ability to remove
      bisphenol A [2, 2-bis(4-hydroxyphenyl)propane; BPA], which is known as an
      endocrine disrupter. Nine strains of the lactococci tested could remove BPA from
      media during growth, although the removal ratio was below 9%. When BPA was
      incubated with lyophilized cells of lactococci for 1 h, the concentration of BPA
      in the media was decreased by 9-62%. Especially, the highest removal ratio of BPA
      was observed for Lactococcus lactis subsp. lactis 712. The lactococci could
      adsorb BPA but not degrade it, because the lactococci maintained the ability to
      remove BPA from the medium after autoclaving. When the lyophilized cells of L.
      lactis subsp. lactis 712 were also incubated with six analogues of BPA, they
      effectively adsorbed hydrophobic compounds such as 2, 2'-diphenylpropane and
      bisphenol A dimethylether. The BPA-adsorbing ability of lactococci could be due
      to the hydrophobic binding effect. The removal ratio of BPA by L. lactis subsp.
      lactis 712 was increased after treatment with sodium dodecyl sulfate and
      decreased after digestion with trypsin. These results suggest that the
      hydrophobic proteins on cell surface may be involved in the BPA-adsorbing ability
      of lactococci.

PMID- 17021872
TI  - Cryopreservation of transgenic rice suspension cells producing recombinant
      hCTLA4Ig.
AB  - Transgenic suspension cells of Oryza sativa L. cv. Dongjin utilized as a host for
      producing recombinant human cytotoxic T-lymphocyte antigen 4-immunoglobulin
      (hCTLA4Ig) were preserved in liquid nitrogen (-196 degrees C) after slow
      prefreezing in a deep freezer (-70 degrees C). The development of an optimal
      procedure for long-term storage was investigated by the addition of various
      concentrations of cryoprotectant mixture and osmoticum in preculture media before
      cooling. A pre-deep-freezing time of 120 min was the most effective for
      maintaining cell viability. Compared with mannitol, sorbitol, trehalose, and NaCl
      under the same osmotic conditions, 0.5 M sucrose was found to be the best
      osmoticum for preculture media. The cryoprotectant comprising sucrose, glycerol,
      and dimethylsulfoxide (DMSO) was applied to the precultured cells, and a
      combination of 1 M sucrose, 1 M glycerol, and 1 M DMSO provided the best result.
      The viability with this optimized condition was 88% after cryocell-banking for 1
      day. The expression of hCTLA4Ig in recovered callus from cryopreservation was
      also kept stable, and the production level was similar to that observed in
      noncryopreserved cultures.

PMID- 17021873
TI  - Cloning and functional expression of thermostable beta-glucosidase gene from
      Thermoascus aurantiacus.
AB  - A thermostable beta-glucosidase (BGLI) was purified from Thermoascus aurantiacus
      IFO9748, and the gene (bgl1) encoding this enzyme was cloned and expressed in
      yeast Pichia pastoris. The deduced amino acid sequence encoded by bgl1 showed
      high similarity with the sequence of glycoside hydrolase family 3. The
      recombinant enzyme was purified and subjected to enzymatic characterization.
      Recombinant BGLI retained more than 70% of its initial activity after 1 h of
      incubation at 60 degrees C and was stable in the pH range 3-8. The optimal
      temperature for enzyme activity was about 70 degrees C and the optimal pH was
      about 5. P. pastoris expressing recombinant BGLI became able to utilize
      cellobiose as a carbon source.

PMID- 17021874
TI  - Overexpressing GLT1 in gpd1Delta mutant to improve the production of ethanol of
      Saccharomyces cerevisiae.
AB  - To improve ethanol production in Saccharomyces cerevisiae, two yeast strains were
      constructed. In the mutant, KAM-4, the GPD1 gene, which encodes a glycerol 3
      phosphate dehydrogenase of S. cerevisiae to synthesize glycerol, was deleted. The
      mutant KAM-12 had the GLT1 gene (encodes glutamate synthase) placed under the
      PGK1 promoter while harboring the GPD1 deletion. Notably, overexpression of GLT1
      by the PGK1 promoter along with GPD1 deletion resulted in a 10.8% higher ethanol
      production and a 25.0% lower glycerol formation compared to the wild type in
      anaerobic fermentations. The growth rate of KAM-4 was slightly lower than that of
      the wild type under the exponential phase whereas KAM-12 and the wild type were
      indistinguishable in the biomass concentration at the end of growth period.
      Meanwhile, dramatic reduction of formation of acetate and pyruvic acid was
      observed in all the mutants compared to the wild type.

PMID- 17021875
TI  - Agrobacterium-mediated transformation (AMT) of Trichoderma reesei as an efficient
      tool for random insertional mutagenesis.
AB  - Filamentous fungus Trichoderma reesei QM9414 was successfully transformed with
      Agrobacterium tumefaciens AGL-1 for random integration of transforming DNA (T
      DNA). Co-cultivation of T. reesei conidia or protoplasts with A. tumefaciens in
      the presence of acetosyringone resulted in the formation of hygromycin B
      resistant fungal colonies with high transformation frequency. Nine randomly
      selected resistant clones were proved to be stable through mitotic cell division.
      The integration of the hph gene into T. reesei genome was determined by PCR and
      dot blot analysis. Transgenic T. reesei strains were analyzed using TAIL-PCR for
      their T-DNA contents. The results showed that T-DNA inserts occurred evidently by
      fusing DNA at T-DNA borders via random recombination, which suggests that
      Agrobacterium-mediated transformation is a potentially powerful tool towards
      tagged mutagenesis and gene transfer technology for T. reesei.

PMID- 17021876
TI  - Effects of environmental settings on MTBE removal for a mixed culture and its
      monoculture isolation.
AB  - A mixed culture was utilized to evaluate methyl tert-butyl ether (MTBE) removal
      under various conditions and to isolate a MTBE-degrading pure culture. The
      results showed that high MTBE removal efficiencies can be reached even in the
      presence of other substrates. The biodegradation sequence of the target compounds
      by the mixed culture, in order of removal rate, was toluene, ethyl benzene, p
      xylene, benzene, MTBE, ethyl ether, tert-amyl methyl ether, and ethyl tert-butyl
      ether. In addition, preincubation of the mixed cultures with benzene and toluene
      showed no negative effect on MTBE removal; on the contrary, it could even
      increase the degradation rate of MTBE. The kinetic behavior showed that the
      maximum specific growth rate and the saturation constant of the mixed culture
      degrading MTBE are 0.000778 h(-1) and 0.029 mg l(-1), respectively. However, a
      high MTBE concentration (60 mg l(-1)) was slightly inhibiting to the growth of
      the mixed culture. The pure culture isolated from the enrichments in the bubble
      air bioreactor showed better efficiency in MTBE removal than the mixed culture;
      whereas, tert-butyl alcohol was formed as a metabolic intermediate during the
      breakdown of MTBE.

PMID- 17021877
TI  - Determination of copper binding in Pseudomonas putida CZ1 by chemical
      modifications and X-ray absorption spectroscopy.
AB  - Previously performed studies have shown that Pseudomonas putida CZ1 biomass can
      bind an appreciable amount of Cu(II) and Zn(II) ions from aqueous solutions. The
      mechanisms of Cu- and Zn-binding by P. putida CZ1 were ascertained by chemical
      modifications of the biomass followed by Fourier transform infrared and X-ray
      absorption spectroscopic analyses of the living or nonliving cells. A dramatic
      decrease in Cu(II)- and Zn(II)-binding resulted after acidic methanol
      esterification of the nonliving cells, indicating that carboxyl functional groups
      play an important role in the binding of metal to the biomaterial. X-ray
      absorption spectroscopy was used to determine the speciation of Cu ions bound by
      living and nonliving cells, as well as to elucidate which functional groups were
      involved in binding of the Cu ions. The X-ray absorption near-edge structure
      spectra analysis showed that the majority of the Cu was bound in both samples as
      Cu(II). The fitting results of Cu K-edge extended X-ray absorption fine structure
      spectra showed that N/O ligands dominated in living and nonliving cells.
      Therefore, by combining different techniques, our results indicate that carboxyl
      functional groups are the major ligands responsible for the metal binding in P.
      putida CZ1.

PMID- 17021878
TI  - The construction and characterization of a bifunctional EGFP/sAPRIL fusion
      protein.
AB  - A fusion protein of enhanced green fluorescent protein (EGFP) and soluble domain
      of human a proliferation-inducing ligand (sAPRIL) was efficiently expressed in
      Escherichia coli BL 21 (DE3). The soluble EGFP/sAPRIL, around 43 kDa, was
      purified in milligram amounts using metal chellate affinity chromatography and
      detected with anti-His(6) and anti-hsAPRIL monoclonal antibody. The chimeric
      protein exhibited similar fluorescence spectra with free EGFP. In vitro, purified
      EGFP/sAPRIL specifically bound receptor B cell maturation antigen (BCMA) detected
      by enzyme linked immunosorbent assay (ELISA) and receptors [including heparan
      sulfate proteoglycan (HSPGs)]-positive cell lines analyzed by fluorescence
      activated cell sorting (FACS). Confocal laser microscopy images visibly showed
      the HSPGs'-dependent binding of EGFP/sAPRIL to NIH-3T3 cell. In addition, the
      chimera retained the bioactivity to stimulate/co-stimulate proliferation of NIH
      3T3 and Jurkat cell/human B cell in vitro. Therefore, the fusion protein shows a
      readily obtainable source of biologically active sAPRIL which has considerable
      potential for single-step fluorescence detection assay in the study of APRIL and
      its receptors.

PMID- 17021879
TI  - Metabolic pathways and biotechnological production of L-cysteine.
AB  - L-Cysteine is an important amino acid both biologically and commercially.
      Although most amino acids are commercially produced by fermentation, cysteine is
      mainly produced by protein hydrolysis. However, synthetic or biotechnological
      products have been preferred in the market. Biotechnological processes for
      cysteine production, both enzymatic and fermentative processes, are discussed.
      Enzymatic process, the asymmetric hydrolysis of DL-2-amino-Delta(2)-thiazoline-4
      carboxylic acid to L-cysteine, has been developed and industrialized. The L
      cysteine biosynthetic pathways of Escherichia coli and Corynebacterium
      glutamicum, which are used in many amino acid production processes, are also
      described. These two bacteria have basically same L-cysteine biosynthetic
      pathways. L-Cysteine-degrading enzymes and L-cysteine-exporting proteins both in
      E. coli and C. glutamicum are also described. In conclusion, for the effective
      fermentative production of L-cysteine directly from glucose, the combination of
      enhancing biosynthetic activity, weakening the degradation pathway, and
      exploiting the export system seems to be effective.

PMID- 17021880
TI  - A direct and efficient PAGE-mediated overlap extension PCR method for gene
      multiple-site mutagenesis.
AB  - A simple, two-step efficient method to perform multiple-site mutagenesis of a
      gene from bacterial genome was developed. The method was named polyacrylamide gel
      electrophoresis (PAGE)-mediated overlap extension polymerase chain reaction (PCR)
      (POEP). The first step involves synthesis of individual fragments containing
      mutant sites with 15- to 25-bp overlap between two adjacent fragments. Mutations
      were introduced into the overlapping oligonucleotide primers which ensured the
      particular primer-template annealing. PAGE was used to remove contaminating
      parental templates, mispriming fragments, and leftover primers. The second step
      involves synthesis of the mutant full-length fragment. All purified PCR products
      from the first step were combined and used as the template for a second PCR using
      high-fidelity DNA polymerase, with the two outermost flanking oligonucleotides as
      primers. Using the POEP method, we have successfully introduced eight EcoRI sites
      into the Escherichia coli beta-galactosidase (Lac Z) gene. The overall rate of
      obtaining the multiple mutant sites was 100%. The POEP method is simple,
      involving only two steps, and reliable for multiple-site mutagenesis and is
      promising to be widely used in gene modification.

PMID- 17021882
TI  - In vitro evaluation of the prebiotic activity of a pectic oligosaccharide-rich
      extract enzymatically derived from bergamot peel.
AB  - The prebiotic effect of a pectic oligosaccharide-rich extract enzymatically
      derived from bergamot peel was studied using pure and mixed cultures of human
      faecal bacteria. This was compared to the prebiotic effect of fructo
      oligosaccharides (FOS). Individual species of bifidobacteria and lactobacilli
      responded positively to the addition of the bergamot extract, which contained
      oligosaccharides in the range of three to seven. Fermentation studies were also
      carried out in controlled pH batch mixed human faecal cultures and changes in gut
      bacterial groups were monitored over 24 h by fluorescent in situ hybridisation, a
      culture-independent microbial assessment. Addition of the bergamot
      oligosaccharides (BOS) resulted in a high increase in the number of
      bifidobacteria and lactobacilli, whereas the clostridial population decreased. A
      prebiotic index (PI) was calculated for both FOS and BOS after 10 and 24 h
      incubation. Generally, higher PI scores were obtained after 10 h incubation, with
      BOS showing a greater value (6.90) than FOS (6.12).

PMID- 17021884
TI  - [Dolasetron and shivering. A prospective randomized placebo-controlled pharmaco
      economic evaluation].
AB  - BACKGROUND AND GOAL: Forced by the current economical situation, German hospitals
      have to reconsider their clinical productivity. When caregivers introduce new
      therapeutic concepts medical quality should either be improved without increasing
      costs or when reducing costs medical quality should be maintained. In the
      surgical field postoperative shivering reduces both patient comfort and medical
      quality. We therefore investigated the clinical pathway prevention of shivering
      with dolasetron in a prospective, randomized, placebo-controlled analysis of cost
      effectiveness. MATERIAL AND METHODS: After written informed consent we randomized
      40 patients scheduled for lumbar disc hernia repair or head and neck surgery into
      two groups: patients of group D received dolasetron 1 mg/kg body weight during
      surgery whereas patients of group K received 100 ml saline as placebo. Primary
      endpoints were the incidence of shivering, the length of stay in the
      postanesthesia care unit and process-associated costs. Secondary endpoint was the
      influence on perioperative thermoregulation. RESULTS: We observed postanesthetic
      shivering in 5 patients belonging to group D in comparison to 15 patients
      receiving the placebo (p<0.05). The length of stay in the postanesthesia care
      unit was shorter in patients allocated to dolasetron (mean+/-SD; group D: 43+/-16
      min, group K 62+/-18 min, p<0.05). There was a significant saving in process
      associated personnel costs (personnel costs in group D EUR 41.26+/-14, personnel
      costs in group K EUR 53.15+/-15) but in contrast the process-associated material
      costs were significantly increased (group D EUR 17.16+/-3, group K EUR 0.73+/-1,
      p<0.05). CONCLUSIONS: The optimization of the clinical process and medical
      quality induced by a prophylaxis against shivering and postoperative nausea and
      vomiting compensates for the increased use of pharmaceutical resources in our
      setting.

PMID- 17021885
TI  - [Public access defibrillation. Limited use by trained first responders and
      laymen].
AB  - As ventricular fibrillation is the most frequent initial heart rhythm causing out
      of-hospital sudden cardiac arrest, defibrillation is of essential significance.
      Automated external defibrillators (AEDs) have been available for some years and
      as a result defibrillation can be carried out by individuals other than
      physicians and healthcare providers such as trained first responders and
      untrained lay rescuers. This so-called public access defibrillation nourished
      hope of progress in the treatment of sudden cardiac arrest. However, several
      limitations exist, such as low frequency of sudden cardiac arrest in public, rare
      use of publicly placed AEDs, low cost effectiveness, legal requirements and
      insufficient public willingness to help. Due to these restrictions of public
      access defibrillation other measures are more promising than the attempt at
      general distribution of AEDs. These measures are primary or secondary prophylaxis
      of sudden cardiac arrest, general knowledge of adequate activation of emergency
      medical services, implementation of first responder teams equipped with AEDs and
      particularly a better education in and application of the well-established
      principles of cardiopulmonary resuscitation.

PMID- 17021886
TI  - [Oxygen therapy in diving accidents].
AB  - Diving accidents represent a departure from the routine practice of emergency
      physicians. The incidence of non-fatal diving accidents is reported as 1-2 per
      10,000 dives. Apart from adequate intravenous hydration, oxygen is the only
      medication with a proven effect in the treatment of diving accidents. After a
      typical diving accident, administration of oxygen at an inspired concentration
      (F(I)O(2) 1.0) as high as possible is recommended. Many divers bring along their
      own oxygen administration systems to the diving sites and these are often better
      suited for the treatment of diving accidents than the oxygen systems of many
      emergency responders. Pressure regulators supplying low constant flow oxygen,
      nasal prongs and inhalation masks are inappropriate. When using artificial
      ventilation bags with face masks, an oxygen flow of at least 15 l/min should be
      used. Demand regulators are simple to use and able to deliver a F(I)O2 of 1.0.
      Their ease of use has earned them high marks in the emergency management of
      diving accidents and their similarity to standard diving equipment has also aided
      relatively widespread acceptance. Circulation breathing systems are more
      technologically complex oxygen delivery systems which permit CO2 absorption and
      re-breathing at low oxygen flow. In contrast to the demand modules, the
      likelihood of mistakes during their usage is higher. In diving accidents, the
      administration of normobaric oxygen, already begun in the field, is the most
      important therapy and should not be interrupted. Presented with an inadequate
      supplemental oxygen supply, the inspired oxygen concentration should not be
      decreased, rather the duration of the oxygen administration should be reduced.
      Hyperbaric oxygen therapy should be the mainstay of further treatment.

PMID- 17021881
TI  - Large-scale identification of transcripts expressed in a symbiotic fungus
      (Termitomyces) during plant biomass degradation.
AB  - Fungus-growing termites have a symbiotic relationship with the basidiomycetes of
      the genus Termitomyces. This symbiotic system is able to degrade dead plant
      material efficiently. We conducted expressed sequence tag (EST) analysis of a
      symbiotic Termitomyces fungus degrading plant material in a field nest of the
      termite Macrotermes gilvus. A subtractive cDNA library was also investigated to
      facilitate the discovery of genes expressed specifically under the symbiotic
      conditions. A total of 2,613 ESTs were collected and resulted in 1,582
      nonredundant tentative consensus sequences, of which approximately 59% showed
      significant similarity to known protein sequences. A number of homologous
      sequences to genes involved in plant cell wall degradation were identified and a
      majority of them encoded putative pectinolytic enzymes. Real-time quantitative
      reverse transcriptase polymerase chain reaction analyses confirmed significant
      upregulation of putative stress response genes under symbiotic conditions. The
      present ESTs database provides a valuable resource for molecular biological study
      of plant material degradation in the symbiosis between termites and fungi.

PMID- 17021887
TI  - [Echocardiography during acute hemodynamic instability].
AB  - In light of the growing proportion of illness in the general population, the
      complexity of modern surgery requires precise perioperative hemodynamic
      monitoring. Echocardiography has emerged over the past 15 years as an especially
      valuable diagnostic instrument for intensive medicine. No other monitoring
      technique provides in such a short time, with so little invasiveness, so much
      additional anatomic information for determining the cause of acute hemodynamic
      instability. There is of course the possibility of proceeding transthoracally at
      first, with poor imaging quality but noninvasively, or transesophageally.
      However, perioperative hemodynamic monitoring allows even less experienced
      operators to detect the various differential diagnoses of acute hemodynamic
      instability with an easily managed number of standard images. Starting from the
      first standard settings, depending on pathology the imaging should continue
      selectively with transthoracal echocardiography in the short parasternal axis or
      transesophageal echocardiography in the transgastral short midpapillary axis.

PMID- 17021888
TI  - [Propofol infusion syndrome].
AB  - The propofol infusion syndrome is a rare but potentially lethal complication
      resulting from a prolonged continuous administration of propofol. It was first
      described in the beginning of the 1990's and in recent years there have been
      frequent reports of problems in association with the use of propofol sedation.
      The cardinal signs and symptoms of the propofol infusion syndrome are metabolic
      acidosis, rhabdomyolysis, renal failure, cardiac arrhythmias and a progressive,
      often therapy-resistant cardiac failure. The pathophysiology of this syndrome
      appears to involve a disturbance of mitochondrial metabolism induced by propofol.
      Our report involves a case of propofol infusion syndrome in a patient having
      undergone cardiac surgery.

PMID- 17021889
TI  - Clinical, social and relational determinants of paediatric ambulatory drug
      prescriptions due to respiratory tract infections in Italy.
AB  - OBJECTIVES: Collecting information on patterns of drug prescriptions and on
      factors influencing prescribing decisions is fundamental for supporting the
      rational use of drugs. This study was aimed at investigating patterns of drug
      prescription in paediatric outpatients and at evaluating determinants of
      prescriptions for respiratory tract infections (RTIs). METHODS: We conducted a
      national cross-sectional survey involving primary care paediatricians and
      parents. Diagnoses and prescriptions made at each consultation were described.
      Poisson regression models were used to analyse determinants of drug and
      antibiotic prescriptions for visits due to RTIs. RESULTS: A total of 4,302
      physician and parent questionnaires were analysed. These corresponded to 2,151
      visits, 792 of which were due to RTIs. Drugs were prescribed in 83.4% of RTI
      visits, while antibiotics were prescribed in 40.4%. According to paediatricians'
      perceptions, 84.2% of parents of children with a RTI expected to receive a drug
      prescription. Paediatricians' perception of parental expectations was the
      strongest determinant for prescription of drugs and specifically of antibiotics
      [adjusted relative risk (RR): 1.7 and 3.6, respectively; P < 0.001]. However, in
      77.1% of RTI visits, paediatricians judged themselves as not being influenced at
      all by parents' expectations in their decision to prescribe. CONCLUSIONS: This
      study underscores that relational factors, in particular perceived parental
      expectations, are one of the leading factors of drug prescriptions in paediatric
      ambulatory care settings, reinforcing the opinion that communication between
      physicians and parents can affect prescription patterns.

PMID- 17021890
TI  - Are computerised monitoring systems of value to improve pharmacovigilance in
      paediatric patients?
AB  - OBJECTIVE: The aim of the present study was to evaluate a computerised monitoring
      system (CMS) based on laboratory test results for the detection of adverse drug
      reactions (ADRs) on a paediatric ward. METHODS: A prospective, 6-month
      pharmacoepidemiological survey was performed on a 22-bed paediatric isolation
      ward. ADRs were identified by intensive chart review. In addition to spontaneous
      reporting by the treating physician, automatic laboratory signals generated by a
      CMS were evaluated for their association with ADRs. ADRs were classified by the
      affected target organs according to the WHO-ART system organ classes. RESULTS: A
      total of 73 ADRs were identified in 439 admissions (396 patients) by chart
      review. The CMS alerted 31 (42.4%) ADRs while 23 (31.5%) ADRs were found solely
      by treating physicians. Eight ADRs were detected by both approaches resulting in
      a total detection rate of 74% (compared with intensive pharmacovigilance). Out of
      a total of 27,434 laboratory tests performed routinely, 1,563 were classified as
      abnormal by the predefined CMS and used as the basis of alerts. The sensitivity
      of the system with respect to patients alerted was 90.3% and the specificity only
      19.6%. CONCLUSION: This study demonstrates that, using CMS, a different kind of
      mild adverse events were detected compared to the observation by the treating
      physician. The system presented appears to be sufficiently sensitive, but the
      specificity is too low to make it acceptable for physicians in daily practice. In
      children, clinically important ADRs can be detected best by intensified
      surveillance.

PMID- 17021891
TI  - Heroin-using drivers: importance of morphine and morphine-6-glucuronide on late
      clinical impairment.
AB  - OBJECTIVE: To evaluate the relationship between major heroin metabolites
      (morphine, morphine-6-glucoronide), pattern of drug use, and late impairment of
      psychomotor functions. METHODS: From the database of the Norwegian Institute of
      Public Health, Oslo, blood morphine concentration in samples from heroin users
      (n=70) containing only morphine were correlated with results of the clinical test
      for impairment (CTI). For comparison, test results were explored in individuals
      without any positive analytical finding in blood samples (n=79) selected from the
      same database. RESULTS: In the "no drug" cases, 86% were judged as not impaired
      and 14% as impaired. In the morphine only cases, 20% were judged as not impaired,
      and 80% as impaired. Both daily users and non-daily users had the same proportion
      of impaired cases. Median blood morphine concentration (M) was 0.09 micromol/l in
      the "not impaired" group and 0.15 micromol/l in the "impaired" group (P=0.067).
      For morphine-6-glucuronide (M6G), the median blood concentration was 0.09
      micromol/l in the "not impaired" group and 0.14 micromol/l in the "impaired"
      group (P=0.030). A significant correlation between concentration quartiles and
      number of cases determined as "impaired" was found for M6G (P=0.018) and for the
      sum M+M6G (P=0.013). CONCLUSION: In our population of heroin-drugged drivers,
      blood concentrations of M6G and the sum M+M6G appeared to have concentration
      dependent effects on the CNS that may lead to impairment as judged from a CTI.
      Variations in pattern of use did not seem to have any bearing on the judgement of
      impairment.

PMID- 17021892
TI  - Medicines for children licensed by the European Medicines Agency (EMEA): the
      balance after 10 years.
AB  - OBJECTIVE: The 1995-2005 balance of EMEA activities in the field of paediatric
      medicines was evaluated, taking into account the number both of drugs authorised
      for children and paediatric studies supporting the Marketing Authorisation (MA).
      METHODS: Data on drugs authorised by EMEA were extracted from EPARs (European
      Public Assessment Reports). Active substance, year of approval, anatomical,
      therapeutic and chemical (ATC) code, indication, orphan status, ages, and
      registrative clinical studies characteristics were assessed. RESULTS: The
      percentage of authorised substances for paediatrics is 33.3%. This percentage
      decreased or increased when different subsets of medicines were considered
      [medicines for children under 2 years (23.4%), N-ATC code drugs (6%) and orphan
      drugs (46.4%)]. A total of 165 trials were included in the MA dossiers of 51
      drugs at the time of approval, and additional 22 studies were added to the
      dossiers of 12 active substances submitted for paediatric variations. PK and
      Efficacy/Safety studies were performed for 32 (52%) active substances, while
      either one PK or one Efficacy/Safety study was carried out for 43 (69%) and 45
      (73%) substances, respectively. CONCLUSIONS: This report demonstrates that the
      total number of paediatric medicines approved by EMEA is stable over the 10-year
      period, while an increase in drugs to treat serious or orphan diseases has been
      observed. In addition, under the Centralised Procedure, a valuable number of
      paediatric trials have been submitted to support drug approval.

PMID- 17021893
TI  - Auditory biofeedback substitutes for loss of sensory information in maintaining
      stance.
AB  - The importance of sensory feedback for postural control in stance is evident from
      the balance improvements occurring when sensory information from the vestibular,
      somatosensory, and visual systems is available. However, the extent to which also
      audio-biofeedback (ABF) information can improve balance has not been determined.
      It is also unknown why additional artificial sensory feedback is more effective
      for some subjects than others and in some environmental contexts than others. The
      aim of this study was to determine the relative effectiveness of an ABF system to
      reduce postural sway in stance in healthy control subjects and in subjects with
      bilateral vestibular loss, under conditions of reduced vestibular, visual, and
      somatosensory inputs. This ABF system used a threshold region and non-linear
      scaling parameters customized for each individual, to provide subjects with pitch
      and volume coding of their body sway. ABF had the largest effect on reducing the
      body sway of the subjects with bilateral vestibular loss when the environment
      provided limited visual and somatosensory information; it had the smallest effect
      on reducing the sway of subjects with bilateral vestibular loss, when the
      environment provided full somatosensory information. The extent that all subjects
      substituted ABF information for their loss of sensory information was related to
      the extent that each subject was visually dependent or somatosensory-dependent
      for their postural control. Comparison of postural sway under a variety of
      sensory conditions suggests that patients with profound bilateral loss of
      vestibular function show larger than normal information redundancy among the
      remaining senses and ABF of trunk sway. The results support the hypothesis that
      the nervous system uses augmented sensory information differently depending both
      on the environment and on individual proclivities to rely on vestibular,
      somatosensory or visual information to control sway.

PMID- 17021894
TI  - Motor sequence consolidation: constrained by critical time windows or competing
      components.
AB  - Skill improvements may develop between practice sessions during memory
      consolidation. Skill enhancement within an egocentric coordinate frame develops
      over wake, whereas skill enhancement in an allocentric coordinate frame develops
      over a night of sleep. We tested whether both types of improvement could develop
      over two different 24-h intervals: 8 am to 8 am or from 8 pm to 8 pm. We found
      that for each 24 h interval, only one type of skill improvement was seen. Despite
      passing through wake and a night of sleep participants only showed skill
      improvements commensurate with either a night of sleep or a day awake. The nature
      of the off-line skill enhancement was determined by when consolidation occurred
      within the normal sleep-wake cycle. We conclude that motor sequence consolidation
      is constrained either by having critical time windows or by a competitive
      interaction in which improvements within one co-ordinate frame actively block
      improvements from developing in the alternative co-ordinate frame.

PMID- 17021895
TI  - Motion sickness, body movement, and claustrophobia during passive restraint.
AB  - Standing participants were passively restrained and exposed to oscillating visual
      motion. Thirty-nine percent of participants reported motion sickness. Despite
      passive restraint, participants exhibited displacements of the center of
      pressure, and prior to the onset of motion sickness the evolution of these
      displacements differed between participants who later became sick and those who
      did not. Claustrophobia occurred during restraint, but only among participants
      who became motion sick. The results are consistent with the postural instability
      theory of motion sickness. We discuss the possible relation between
      claustrophobia symptoms, postural movements and motion sickness incidence.

PMID- 17021897
TI  - Cutting crime: the analysis of the "uniqueness" of saw marks on bone.
AB  - Witness marks produced on bone by the use of saws have traditionally been
      examined using stereomicroscopy. The marks are typically found on the kerf wall
      or floor and give important information about the implement that made them. This
      paper describes a new approach to the analysis of witness marks left on kerf
      walls and floors from crimes involving dismemberment. Previously, two types of
      marks have been identified: deep furrows formed during the pull stroke and fine
      striations formed on the push stroke. These types of striation allow the class of
      saw to be identified, but not an individual saw. With the advent of environmental
      scanning electron microscopy (ESEM), insulating materials can now be examined
      without the need for conductive coatings to be applied. This allows materials to
      be examined at higher magnifications than those available with stereomicroscopy.
      Here we report on a new, third type of striation that is visible at higher
      magnifications on ESEM images. These striations are formed from the imperfections
      on the cutting teeth of saws and give real possibilities of uniquely identifying
      whether or not a particular saw was used to cause the mark. In blind trials
      conducted on sawing of nylon 6.6, different individual saws could be successfully
      identified even if different people used the saw. We discuss ways in which these
      results can be extended to bone and how this may assist in the investigation of
      the act of dismemberment.

PMID- 17021896
TI  - Space motion sickness.
AB  - Motion sickness remains a persistent problem in spaceflight. The present review
      summarizes available knowledge concerning the incidence and onset of space motion
      sickness and aspects of the physiology of motion sickness. Proposed etiological
      factors in the elicitation of space motion sickness are evaluated including fluid
      shifts, head movements, visual orientation illusions, Coriolis cross-coupling
      stimulation, and otolith asymmetries. Current modes of treating space motion
      sickness are described. Theoretical models and proposed ground-based paradigms
      for understanding and studying space motion sickness are critically analyzed.
      Prediction tests and questionnaires for assessing susceptibility to space motion
      sickness and their limitations are discussed. We conclude that space motion
      sickness does represent a form of motion sickness and that it does not represent
      a unique diagnostic entity. Motion sickness arises when movements are made during
      exposure to unusual force backgrounds both higher and lower in magnitude than 1 g
      earth gravity.

PMID- 17021898
TI  - Aconitine involvement in an unusual homicide case.
AB  - We describe a homicide complicated by an aconitine poisoning, which was initially
      thought to be a strangulation case. Routine toxicological analyses demonstrated
      only a small amount of alcohol in the blood and the urine. The case could not be
      clarified until 5 years after the event. A new element in the investigation made
      the wife the prime suspect, and finally, after thorough interrogation, she
      confessed her crime. She had mixed a decoction of three plants of Aconitum with
      red wine. Additional toxicological analyses, using the liquid chromatography
      tandem mass spectrometry (LC-MS-MS) technique demonstrated 810 ng/ml of aconitine
      in urine, 6.5 ng/g in liver and 1.3 ng/g in the kidneys. Even though aconitine
      poisoning is still rare in Europe, it should be taken into account in suicides
      and homicides, particularly in unclarified cases.

PMID- 17021900
TI  - [Tetanus vaccination in the accident and emergency department].
AB  - While tetanus is a rare disease in industrialized countries, this infectious
      disease is still responsible for up to 1,000,000 deaths per year in the
      developing world. In Germany, the introduction of a country-wide vaccination
      program (STIKO) has led to a decrease in the frequency of tetanus infection from
      115 cases per year in the 1960s to fewer than 15 cases per year in the years from
      1990 to 2000. In spite of all the treatment now available, tetanus infection
      still has a lethal outcome in up to 40% of cases. The Robert-Koch Institute
      recommends active or passive vaccination depending on the wound classification
      and the patient's current vaccination status. Since when patients have multiple
      trauma the emphasis while they are being treated for shock is on stabilisation
      and diagnosis, there is a real risk of underestimating the size and the level of
      contamination of existing wounds. Since it is not possible to ascertain the
      patient's vaccination status in most cases, we recommend simultaneous
      immunization of polytraumatized patients with skin lesions using Tetanol-Tetagam
      early in the course of the diagnostic procedures while the patients are still in
      the emergency room.

PMID- 17021899
TI  - Medicolegal aspects of tetrazepam metabolism.
AB  - The benzodiazepine tetrazepam is primarily muscle relaxant with comparably lower
      central sedating effects and is therefore commonly prescribed for muscle spasms
      of different origins. To evaluate tetrazepam metabolism, a study was conducted
      with ten healthy volunteers. Blood and urine samples were regularly collected
      after the intake of 50 mg tetrazepam. Toxicological analyses revealed that
      tetrazepam is also metabolized to diazepam and further to nordazepam, which has
      not yet been reported. Tetrazepam and diazepam could be detected in urine samples
      at least 72 h after intake, the diazepam concentration being 33% (+/-14% SD), on
      average, of the tetrazepam concentration. On the basis of three case histories,
      the importance of the detection of these newly described metabolites is shown as
      necessary to prevent false accusations and potential negative legal consequences
      for examined persons.

PMID- 17021901
TI  - Tuberculous bicipitoradial bursitis: a case report.
AB  - An 76-year-old man with an indolent soft tissue mass on the volar aspect of the
      left elbow was referred to our institution with a diagnosis of a soft tissue
      tumor. He had a history of lung tuberculosis since the age of 30. The mass was
      adjacent to the biceps brachi tendon. It demonstrated homogeneous low-signal
      intensity on T1-weighted magnetic resonance (MR) images and heterogeneous
      relatively high signal intensity with scattered low and high signal intensity
      areas on T2-weighted MR images. An excision was performed after needle biopsy
      with presumptive diagnosis of bicipitoradial bursitis. The histological specimen
      revealed an epithelioid cell granuloma with central necrosis. While the
      occurrence of tuberculous bicipitoradial bursitis has never been reported, this
      case demonstrates that it can be considered to be among the causes of a cystic
      lesion around the elbow joint.

PMID- 17021902
TI  - Distal clavicular osteolysis: MR evidence for subchondral fracture.
AB  - PURPOSE: To investigate the association between distal clavicular osteolysis and
      subchondral fractures of the distal clavicle at MRI. MATERIALS AND METHODS: This
      study was approved by the hospital human research committee, which waived the
      need for informed consent. Three radiologists retrospectively analyzed 36
      shoulder MR examinations in 36 patients with imaging findings of distal
      clavicular osteolysis. The presence of a subchondral fracture of the distal
      clavicle, abnormalities of the acromioclavicular joint, rotator cuff tears and
      labral tears were assessed by MRI. These cases were then compared with 36 age
      matched controls. RESULTS: At MRI, 31 of 36 patients (86%) had a subchondral line
      within the distal clavicular edema, consistent with a subchondral fracture. Of
      the 36 patients, 32 (89%) had fluid in the acromioclavicular joint, while 27 of
      36 patients (75%) had cysts or erosions in the distal clavicle. There were 13
      patients (36%) with associated labral tears, while eight patients (22%) had
      partial-thickness rotator cuff tears. In the control group one of 36 (3%) had a
      subchondral line (P<0.05), while ten of 36 (28%) had rotator cuff tears and 13 of
      36 (36%) had labral tears. These latter two were not statistically significant
      between the groups. CONCLUSION: A distal clavicular subchondral fracture is a
      common finding in patients with imaging evidence of distal clavicular osteolysis.
      These subchondral fractures may be responsible for the propensity of findings
      occurring on the clavicular side of the acromioclavicular joint.

PMID- 17021903
TI  - Preliminary experience with transarterial chemoembolization (TACE) in liver
      metastases of uveal malignant melanoma: local tumor control and survival.
AB  - PURPOSE: To evaluate results in the palliative treatment of patients with liver
      metastases of uveal malignant melanoma using transarterial chemoembolization
      (TACE). MATERIALS AND METHODS: Superselective TACE was repeatedly performed in 12
      patients with liver metastases of uveal malignant melanoma. Six patients
      presented with solitary liver metastases (6-12 cm in size) and six patients with
      oligonodular metastases (n < or = 6). The embolization suspension consisted of a
      maximum of 10 mg/m(2) Mitomycin C, 10 ml Lipiodol, and an injection of 200-450 mg
      resorbable microspheres for vascular occlusion. In the follow-up, magnetic
      resonance imaging was performed in 3-month intervals. RESULTS: The TACE procedure
      was well tolerated in all patients without any relevant side effects. Three
      patients responded to TACE with a size reduction of more than 50% (partial
      response), five patients with stable disease, and four patients with progressive
      disease with an increase in volume of more than 25%. Mean survival following
      primary tumor treatment was 32.9 months, and after first embolization 19.5
      months. Lower survival rates were recorded for the progressive group (16.5
      months). CONCLUSION: Repeated TACE offers a palliative treatment option in
      patients with oligonodular liver metastases of uveal malignant melanoma.

PMID- 17021904
TI  - Concurrent use of vinorelbine and gefitinib induces supra-additive effect in head
      and neck squamous cell carcinoma cell lines.
AB  - PURPOSE: Squamous cell carcinoma of the head and neck (HNSCC) remains a clinical
      challenge because of the high rate of locoregional disease recurrence. Standard
      treatment includes surgery, radiation, chemoradiation or a combination of these
      approaches. New therapies are needed to achieve improved survival, quality of
      life and organ function in these patients. A novel molecular targeted therapy
      incorporated into our current treatment strategies may have a significant role in
      the treatment of HNSCC. The aim of this study was to evaluate the sensitivity of
      HNSCC cell lines to vinorelbine combined with gefitinib in vitro. METHODS: Six
      recently established cell lines were used: UT-SCC-9, -11, -19A, -29 and -34
      (laryngeal SCC) and UT-SCC-33 (oral cavity SCC). Chemosensitivity was tested
      using the 96-well plate clonogenic assay. The vinorelbine concentrations used
      varied between 0.4 and 1.0 nM and the gefitinib concentrations varied between
      0.05 and 1.6 muM. Survival data were fitted to the LQ model, and the area under
      the curve (AUC) value was obtained with numerical integration. The type of
      interaction was determined by comparing the AUC ratio of the two drugs to the
      survival fraction (SF) of gefitinib alone. RESULTS: In the current study the
      combination of vinorelbine and gefitinib had a clear supra-additive or additive
      cytotoxic effect on the HNSCC cell lines. CONCLUSIONS: This finding is
      encouraging as a proof of the possible benefit of combing an EGFR targeting
      compound with a cell cycle specific drug and warrants further studies of
      available combinations in vitro.

PMID- 17021905
TI  - [Managing the side effects of angiogenetic inhibitors in metastatic renal cell
      carcinoma].
AB  - Sunitinib and Sorafenib are both effective angiogenetic inhibitors for the
      treatment of renal cell carcinoma. With these drugs of a new class of chronic
      therapy is performed. During chronic treatment, the inherent side effects may
      necessitate stopping the application of these drugs thus preventing the required
      effective therapy. Most of the effects can be avoided or attenuated by
      prophylaxis. In this paper the published data are reviewed and added with our
      experience in 138 patients over up to two and a half years.

PMID- 17021906
TI  - Light and alcohol evoked electro-oculograms in cystic fibrosis.
AB  - Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane
      conductance regulator (CFTR) which is a chloride channel. CFTR is expressed in
      the retinal pigment epithelium (RPE) where it is believed to be important in
      generating the fast oscillations (FOs) and potentially contributing to the light
      electro-oculogram (EOG). The role of CFTR in the alcohol-EOG is unknown. We
      recruited six individuals with CF (three homozygotes for Delta508 and three
      heterozygous for Delta508) and recorded the light- and alcohol-EOGs as well as
      the FOs and compared them to a control group. The results showed that in the CF
      group the amplitude of the alcohol- and light-EOGs were normal. However, the time
      to peak of the light- and alcohol-rises were significantly faster than in the
      control group. We conclude that CFTR is not primarily responsible for the alcohol
      or light-rises but is involved in altering the timing of these responses. The
      FOs showed differences between the homozygotes, heterozygotes and the controls.
      The amplitudes were significantly higher and the time to the dark troughs were
      significantly slower in the heterozygote group compared to both controls and the
      homozygotes. In contrast, the homozygotes did not differ in either amplitude or
      the timing of the FOs compared to the controls.

PMID- 17021907
TI  - The changing face of prostate cancer: can gains in epigenetic knowledge translate
      into improvements in clinical care?

PMID- 17021908
TI  - Thioredoxin in the cardiovascular system.
AB  - The thioredoxin (TRX) system (TRX, TRX reductase, and NADPH) is a ubiquitous
      thiol oxidoreductase system that regulates cellular reduction/oxidation (redox)
      status. The impairment of cell redox state alters multiple cell pathways, which
      may contribute to the pathogenesis of cardiovascular disorders including
      hypertension, atherosclerosis, and heart failure. In this manuscript, we review
      the essential roles that TRX plays by limiting oxidative stress directly via
      antioxidant effects and indirectly by protein-protein interactions with key
      signaling molecules such as thioredoxin interacting protein (TXNIP). TRX and its
      endogenous regulators may represent important future targets to develop clinical
      therapies for diseases associated with oxidative stress.

PMID- 17021909
TI  - [Chronic critical ischemia of the lower leg: pretherapeutic imaging and methods
      for revascularization].
AB  - Each year 1-2% of patients with peripheral arterial occlusive disease (pAOD)
      develop critical limb ischemia (CLI), characterized by rest pain and peripheral
      ulcer or gangrene. This aggravation of the disease is accompanied by an increase
      of the 1-year mortality rate up to 25% and a similarly increased frequency of
      major amputation. We can choose between conservative, endovascular, and surgical
      procedures for an adequate therapy of the underlying vascular stenoses or
      occlusions. Yet, clear therapeutic recommendations only exist for suprapopliteal
      lesions. However, in a number of cases, especially in diabetics, target lesions
      have an infrapopliteal location. Since endovascular procedures have undergone
      significant improvement in the last few years, the following review discusses
      methods for infrapopliteal revascularization taking into consideration the newest
      publications on this topic.

PMID- 17021910
TI  - [CTA and MRA in peripheral arterial disease--is DSA out?].
AB  - New developments in technique and postprocessing have led to further improvement
      in diagnosing and evaluating peripheral arterial disease (PAD) by noninvasive
      computed tomographic angiography (CTA) and magnetic resonance angiography (MRA).
      Under clinical conditions diagnostic conventional angiography (DSA) will be
      increasingly replaced by CTA and MRA. The radiologist has to become familiar with
      the field of indications, the different techniques, postprocessing tools, and
      effective visualization. In consideration of the current literature some
      methodological aspects and the role of CTA and MRA in PAD will be discussed.

PMID- 17021911
TI  - [Absorptiometry].
AB  - This article is an introduction to dual X-ray absorptiometry (DXA), the most
      widely used method today for diagnosis of osteoporosis. DXA can be used to assess
      projective bone mineral density at the lumbar spine, the proximal hip, and the
      whole body as well as the skeletal periphery at the forearm, the hand, and the
      heel. The prominent area of application of DXA is the diagnosis and monitoring of
      osteoporosis and its treatment. Because of its high accuracy, precision, and
      ability to predict osteoporotic fracture as well as its relatively low cost, DXA
      has prevailed over alternative methods. This article discusses the underlying X
      ray physics and technological aspects, acquisition protocols, quality
      characteristics, and sources of error and their relevance. It also describes the
      various skeletal regions accessible to measurement, details on precision, nominal
      results, usability to predict fracture risk, and results of influential clinical
      trials.

PMID- 17021912
TI  - [Introduction to the topic: diagnosis of osteoporosis - a paradigm shift].

PMID- 17021913
TI  - Effect of tunnel inclination on digging energetics in the tuco-tuco, Ctenomys
      talarum (Rodentia: Ctenomyidae).
AB  - Burrows play an important role for many species, providing them with shelter and
      access to food resources. For subterranean rodents, living underground imposes
      constraints on morphology and physiology. The convergence in burrow architecture
      among subterranean rodents has been related to the energy demands imposed by the
      cost of constructing an entire system. The low frequency of tunnels with downward
      angles steeper than 40 degrees appears to be a common feature in burrow design.
      In the subterranean habitat, movements through the soil are expensive and gravity
      can exert important restrictions on digging energetics when individuals push out
      the soil removed in steeper digging angles. The aim of this study was to
      determine the effect of digging angle on digging energetics in Ctenomys talarum.
      The mass of the removed soil and burrowing speed were similar while digging
      metabolic rate and net cost of transport were higher in individuals digging in
      tunnels with angles >40 degrees than in those digging tunnels with angles <40
      degrees . The cost of constructing a burrow in the horizontal plane differed by
      20% from others in which the natural representation of tunnels >40 degrees was
      considered. Even given that tunnels >40 degrees represented only 6% of the total
      burrow length, burrow architecture appears to be constrained by the high
      energetic cost of constructing in steeper angles.

PMID- 17021914
TI  - Taphonomic evidence for high-speed adapted fins in thunniform ichthyosaurs.
AB  - Ichthyosaurs have been compared with the fast-swimming thunniform groups of
      marine vertebrates, tuna, lamnid sharks, and dolphins, based on similarity of
      shape of the body and locomotory organs. In addition to shape, high-tensile
      stiffness of the control surfaces has been shown to be essential in maximizing
      hydrodynamic efficiency in extant thunniform swimmers. To date, there has been no
      evidence of a stiffening support system for the dorsal fin and dorsal lobe of the
      caudal fin in ichthyosaurs, the sole stiffening structure of the ventral lobe
      being an extension of the vertebral column along its leading edge. Stenopterygius
      SMF 457 is arguably the best soft-tissue preserved ichthyosaur specimen known.
      Here, we examine soft-tissue preservation in this specimen in the control
      surfaces and provide the first evidence of a complex architecture of stiff fibers
      in the dorsal and caudal fins. We find by comparisons and by analogy that these
      fibers provided a remarkable mechanism for high tensile stiffness and efficiency
      of the locomotory organs virtually identical to that of the great white shark,
      Carcharodon carcharias. It is the first mechanostructural study of the control
      surfaces of a Jurassic ichthyosaur that adds essential evidence in support of the
      view that these forms were high-speed thunniform swimmers.

PMID- 17021915
TI  - Honeybees learn floral odors while receiving nectar from foragers within the
      hive.
AB  - Recent studies showed that nectar odors brought back by honeybee foragers can be
      learned associatively inside the hive. In the present study, we focused on the
      learning abilities of bees, which directly interact via trophallaxis with the
      incoming nectar foragers: the workers that perform nectar-receiving tasks inside
      the hive. Workers that have received food directly from foragers coming back from
      a feeder offering either unscented or scented sugar solution [phenylacetaldehyde
      (PHE) or nonanal diluted] were captured from two observational hives, and their
      olfactory memories were tested using the proboscis extension response paradigm.
      Bees that have received scented solution from incoming foragers showed
      significantly increased response frequencies for the corresponding solution odor
      in comparison with those that have received unscented solution. No differences in
      the response frequencies were found between food odors and colonies. The results
      indicate that first-order receivers learn via trophallaxis the association
      between the scent and the sugar solution transferred by incoming foragers. The
      implications of these results should be considered at three levels: the
      operational cohesion of bees involved in foraging-related tasks, the information
      propagation inside the hive related to the floral type exploited, and the
      putative effect of these memories on future preferences for resources.

PMID- 17021916
TI  - [Digital slide training portal. Training slides available on the Internet from
      the German division of the IAP].
AB  - Alternatively to sending glass slides via mail order, the German division of the
      IAP established a digital slide training portal on the Internet. Following the
      principle of virtual microscopy, histology slides were scanned completely in high
      resolution, stored on a server, and can be accessed over the Internet. The slide
      training portal can be used with current Internet browsers without additional
      plugins. Working on digital slides with the virtual microscope is easy but
      flexible. Loading a detail image using image streaming technologies takes about
      500 ms with the German research network (DFN) and about 3 s with DSL. The digital
      slide training portal of the German IAP provides a clear choice and is always
      available for every member. Despite the little experience some users had with the
      Internet and diagnostics at the monitor, image quality and usability were rated
      as good.

PMID- 17021917
TI  - [Amyloid diagnostics in rheumatic diseases].
AB  - Amyloid is a pathological protein deposit in tissue which has a red eosin color
      when the slice preparation is stained with traditional hematoxylin and eosin and
      after Congo red staining under polarized light exhibits a characteristic apple
      green polarization color. Over 26 different autologous physiological proteins
      have been described that can form amyloid. In surgical pathology, immunoglobulin
      light chain-associated AL amyloidosis is the most frequent generally occurring
      amyloidosis, followed by hereditary and nonhereditary ATTR amyloidosis and AA
      amyloidosis. AA amyloidosis mostly develops subsequent to chronic infectious or
      inflammatory underlying disease and can represent a potentially life threatening
      complication. The spectrum of causes for AA amyloidosis has changed in the past
      few decades and is now determined by chronic rheumatic diseases and hereditary
      periodic fever syndromes. Early diagnosis of an amyloidosis and its correct
      classification continue to pose a great challenge. Precise classification of the
      amyloid and amyloidosis is essential for prognosis assessment and treatment
      planning. In addition to anti-inflammatory management of AA amyloidosis, specific
      treatment strategies may possibly become available in the future.

PMID- 17021918
TI  - Ethnicity modifies the association between diabetes mellitus and ischaemic heart
      disease in Chinese, Malays and Asian Indians living in Singapore.
AB  - AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of
      ischaemic heart disease (IHD) associated with diabetes mellitus differs between
      ethnic groups. METHODS: Registry linkage was used to identify IHD events in 5707
      Chinese, Malay and Asian Indian participants from three cross-sectional studies
      conducted in Singapore between the years 1984 and 1995. The study provided a
      median of 10.2 years of follow-up with 240 IHD events experienced. We assessed
      the interaction between diabetes mellitus and ethnicity in relation to the risk
      of IHD events using Cox proportional hazards regression. RESULTS: Diabetes
      mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was
      associated with a greater risk of IHD in Asian Indians. The hazard ratio when
      comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77
      7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for
      interaction). Differences in the levels of established IHD risk factors among
      diabetics from the three ethnic groups did not appear to explain the differences
      in IHD risk. CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to
      the development of diabetes mellitus than Chinese and Malays. When Asian Indians
      do develop diabetes mellitus, the risk of IHD is higher than for Chinese and
      Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic
      group is particularly important for the prevention of IHD in Asia, especially
      given the size of the population at risk. Elucidation of the reasons for these
      ethnic differences may help us understand the pathogenesis of IHD in those with
      diabetes mellitus.

PMID- 17021919
TI  - Diabetes mellitus and risk of bladder cancer: a meta-analysis.
AB  - AIMS/HYPOTHESIS: Epidemiological evidence indicates that individuals with
      diabetes mellitus have an increased risk of several cancers. We performed a
      systematic review with meta-analysis to evaluate the association between diabetes
      and risk of bladder cancer. METHODS: Pertinent studies were identified by
      searching MEDLINE (from January 1966 to July 2006) and by reviewing the reference
      lists of retrieved articles. We included case-control and cohort studies
      reporting relative risk (RR) estimates with 95% CIs (or data to calculate them)
      of bladder cancer associated with diabetes. Studies of type 1 diabetes were not
      included. Summary RRs were calculated using a random-effects model. RESULTS: A
      total of 16 studies (seven case-control studies, three cohort studies and six
      cohort studies of diabetic patients) fulfilled the inclusion criteria. Analysis
      of all studies showed that diabetes was associated with an increased risk of
      bladder cancer, compared with no diabetes (RR = 1.24, 95% CI 1.08-1.42). There
      was strong evidence of heterogeneity among these studies (p < 0.0001).
      Stratification by study design found that diabetes was associated with an
      increased risk of bladder cancer in case-control studies (RR = 1.37, 95% CI 1.04
      1.80, p (heterogeneity) = 0.005) and cohort studies (RR = 1.43, 95% CI 1.18-1.74,
      p (heterogeneity) = 0.17), but not in cohort studies of diabetic patients (RR =
      1.01, 95% CI 0.91-1.12, p (heterogeneity) = 0.35). CONCLUSIONS/INTERPRETATION:
      Findings from this meta-analysis suggest that individuals with diabetes may have
      a modestly increased risk of bladder cancer.

PMID- 17021920
TI  - Pancreas transplant alone has beneficial effects on retinopathy in type 1
      diabetic patients.
AB  - AIMS/HYPOTHESIS: The effects of successful pancreas transplant alone (PTA) on
      chronic complications of diabetes, in particular diabetic retinopathy, remain
      disputed. We prospectively studied the course of diabetic retinopathy in PTA
      recipients and in non-transplanted (non-PTA) type 1 diabetic patients. METHODS:
      The PTA and non-PTA groups consisted respectively of 33 (follow-up: 30 +/- 11
      months) and 35 patients (follow-up: 28 +/- 10 months). Best corrected visual
      acuity, slit lamp examination, intraocular pressure measurement, ophthalmoscopy,
      retinal photographs, and in selected cases angiography were performed. Diabetic
      retinopathy and its improvement/deterioration were assessed according to criteria
      proposed by the Eurodiab Study. RESULTS: At baseline, 9% of PTA and 6% of non-PTA
      patients had no diabetic retinopathy, 24 and 29% had non-proliferative diabetic
      retinopathy (NPDR), whereas 67 and 66% had laser-treated and/or proliferative
      diabetic retinopathy (LT/PDR), respectively. No new case of diabetic retinopathy
      occurred in either group during follow-up. In the NPDR PTA group, 50% of patients
      improved by one grading, and 50% showed no change. In the LT/PDR PTA,
      stabilisation was observed in 86% of cases, whereas worsening of retinopathy
      occurred in 14% of patients. In the NPDR non-PTA group, diabetic retinopathy
      improved in 20% of patients, remained unchanged in 10%, and worsened in the
      remaining 70%. In the LT/PDR non-PTA group, retinopathy did not change in 43% and
      deteriorated in 57% of patients. Overall, the percentage of patients with
      improved or stabilised diabetic retinopathy was significantly higher in the PTA
      group. No differences were found between the two groups with regard to cataract
      lesions and intraocular pressure values. CONCLUSIONS/INTERPRETATION: Despite a
      relatively short follow-up, our study shows that successful PTA can positively
      affect the course of diabetic retinopathy.

PMID- 17021921
TI  - The PEA15 gene is overexpressed and related to insulin resistance in healthy
      first-degree relatives of patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Overexpression of the gene encoding phosphoprotein enriched in
      astrocytes 15 (PEA15), also known as phosphoprotein enriched in diabetes (PED),
      causes insulin resistance and diabetes in transgenic mice and has been observed
      in type 2 diabetic individuals. The aim of this study was to investigate whether
      PEA15 overexpression occurs in individuals at high risk of diabetes and whether
      it is associated with specific type 2 diabetes subphenotypes. SUBJECTS AND
      METHODS: We analysed PEA15 expression in euglycaemic first-degree relatives (FDR)
      of type 2 diabetic subjects. RESULTS: The expression of PEA15 in peripheral blood
      leucocytes (PBLs) paralleled that in fat and skeletal muscle tissues. In PBLs
      from the FDR, PEA15 expression was two-fold higher than in euglycaemic
      individuals with no family history of diabetes (control subjects), both at the
      protein and the mRNA level (p < 0.001). The expression of PEA15 was comparable in
      FDR and type 2 diabetic subjects and in each group close to one-third of the
      subjects expressed PEA15 levels more than 2 SD higher than the mean of control
      subjects. Subjects with IFG with at least one type 2 diabetes-affected FDR also
      overexpressed PEA15 (p < 0.05). In all the groups analysed, PEA15 expression was
      independent of sex and unrelated to age, BMI, waist circumference, systolic and
      diastolic BP, and fasting cholesterol, triacylglycerol and glucose levels.
      However, in euglycaemic FDR of type 2 diabetic subjects, PEA15 expression was
      inversely correlated with insulin sensitivity (r = -557, p = 0.01).
      CONCLUSIONS/INTERPRETATION: We conclude that PEA15 overexpression represents a
      common defect in FDR of patients with type 2 diabetes and is correlated with
      reduced insulin sensitivity in these individuals.

PMID- 17021922
TI  - Comparison of different definitions of the metabolic syndrome in relation to
      cardiovascular mortality in European men and women.
AB  - AIMS/HYPOTHESIS: We estimated cardiovascular disease (CVD) mortality in
      individuals with the metabolic syndrome on the basis of different definitions.
      METHODS: We collaboratively analysed data from 4,715 men and 5,554 women, who
      were aged 30 to 89 years, had a maximum follow-up of 7 to 16 years, and were
      drawn from nine European population-based cohorts. Cox regression analysis with
      age as time scale was performed to estimate hazard ratio (HR) for mortality,
      adjusting for cohort, serum total cholesterol and smoking. RESULTS: The
      prevalence of the metabolic syndrome according to definitions of WHO, the
      National Cholesterol Education Program (NCEP), NCEP revised and the International
      Diabetes Federation (IDF) was 27.0%, 25.9%, 32.2% and 35.9% respectively in men
      and 19.7%, 23.4%, 28.5% and 34.1% respectively in women. The corresponding HRs
      (95% CIs) for CVD mortality were 2.09 (1.59-2.76), 1.74 (1.31-2.30), 1.72 (1.31
      2.26) and 1.51 (1.15-1.99) in men, and 1.60 (1.01-2.51), 1.39 (0.89-2.18), 1.09
      (0.70-1.69) and 1.53 (0.99-2.36) in women. The paired homogeneity test showed
      that in men the HR was higher with the WHO definition than with the IDF
      definition (p=0.03). In women the HR was lower with the revised NCEP definitions
      than with either the WHO (p=0.02) or the IDF (p=0.01) definitions. With a few
      exceptions, HRs for full definitions of the syndrome were not significantly
      different from those for their single components. CONCLUSIONS/INTERPRETATION:
      Metabolic syndrome by the four definitions predicted CVD mortality in men, but
      the prediction was weak in women. Further research is required on the utility of
      definitions of the metabolic syndrome above and beyond that of its single
      components and in individual CVD risk stratification, particularly with regard to
      sex difference in the prediction.

PMID- 17021923
TI  - Kinetic and crystallographic studies of a redesigned manganese-binding site in
      cytochrome c peroxidase.
AB  - Manganese peroxidase (MnP) from the white rot fungus Phanerochaete chrysosporium
      contains a manganese-binding site that plays a critical role in its function.
      Previously, a Mn(II)-binding site was designed into cytochrome c peroxidase (CcP)
      based on sequence homology (Yeung et al. in Chem. Biol. 4:215-222, 1997;
      Gengenbach et al. in Biochemistry 38:11425-11432, 1999). Here, we report a
      redesign of this site based on X-ray structural comparison of MnP and CcP. The
      variant, CcP(D37E, V45E, H181E), displays 2.5-fold higher catalytic efficiency (k
      (cat)/K (M)) than the variant in the original design, mostly due to a stronger K
      (M) of 1.9 mM (vs. 4.1 mM). High-resolution X-ray crystal structures of a metal
      free form and a form with Co(II) at the designed Mn(II) site were also obtained.
      The metal ion in the engineered metal-binding site overlays well with Mn(II)
      bound in MnP, suggesting that this variant is the closest structural model of the
      Mn(II)-binding site in MnP for which a crystal structure exists. A major
      difference arises in the distances of the ligands to the metal; the metal-ligand
      interactions in the CcP variant are much weaker than the corresponding
      interactions in MnP, probably owing to partial occupancy of metal ion at the
      designed site, difference in the identity of metal ions (Co(II) rather than
      Mn(II)) and other interactions in the second coordination sphere. These results
      indicate that the metal ion, the ligands, and the environment around the metal
      binding site play important roles in tuning the structure and function of
      metalloenzymes.

PMID- 17021924
TI  - Impairments in water maze learning of aged rats that received dextromethorphan
      repeatedly during adolescent period.
AB  - RATIONALE: Dextromethorphan (DM), an over-the-counter cough suppressant, has been
      recently used as a drug of abuse by teenage groups in some countries, such as the
      United States, Canada, and Korea. We previously showed that repeated
      administration of DM, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)
      receptors, impairs spatial learning performance in adolescent rats. OBJECTIVES:
      In the present study, long-term adverse effects of repetitive DM use at
      adolescence were examined in rats. METHODS: Male and female Sprague-Dawley rat
      pups received either intraperitoneal DM (40 mg/kg) or saline daily during
      postnatal days 28-37, and were then subjected to the Morris water maze task at
      the age of 18 months. Expression levels of NMDAR1, functional subunit of NMDA
      receptors, in the prefrontal cortex and the hippocampus were examined by Western
      blot analysis. Changes in plasma corticosterone levels responding to stress were
      determined by radioimmunoassay. RESULTS: DM-experienced male rats exhibited
      deficits in the probe trial, and female rats in the initial learning and the
      reversal training, in water maze performance. Expression levels of NMDAR1 in the
      brain regions were significantly increased in DM-experienced rats, compared to
      control rats. Stress-induced increases in plasma corticosterone levels were
      blunted both in male and female DM rats. CONCLUSIONS: The results suggest that
      repeated administration of DM at high doses during adolescent period may induce
      permanent deficits in cognitive function and that increased expression of NMDAR1
      in the prefrontal cortex and the hippocampus may take a role in DM-induced memory
      deficits.

PMID- 17021926
TI  - Fractal analysis of contours of breast masses in mammograms.
AB  - Fractal analysis has been shown to be useful in image processing for
      characterizing shape and gray-scale complexity. Breast masses present shape and
      gray-scale characteristics that vary between benign masses and malignant tumors
      in mammograms. Limited studies have been conducted on the application of fractal
      analysis specifically for classifying breast masses based on shape. The fractal
      dimension of the contour of a mass may be computed either directly from the 2
      dimensional (2D) contour or from a 1-dimensional (1D) signature derived from the
      contour. We present a study of four methods to compute the fractal dimension of
      the contours of breast masses, including the ruler method and the box counting
      method applied to 1D and 2D representations of the contours. The methods were
      applied to a data set of 111 contours of breast masses. Receiver operating
      characteristics (ROC) analysis was performed to assess and compare the
      performance of fractal dimension and four previously developed shape factors in
      the classification of breast masses as benign or malignant. Fractal dimension was
      observed to complement the other shape factors, in particular fractional
      concavity, in the representation of the complexity of the contours. The
      combination of fractal dimension with fractional concavity yielded the highest
      area (A ( z )) under the ROC curve of 0.93; the two measures, on their own,
      resulted in A ( z ) values of 0.89 and 0.88, respectively.

PMID- 17021925
TI  - Intact discrimination reversal learning but slowed responding to reward
      predictive cues after dopamine D1 and D2 receptor blockade in the nucleus
      accumbens of rats.
AB  - RATIONALE: The prediction error hypothesis of dopamine action states that
      dopamine signals are necessary for the brain to update the predictive
      significance of cues. Yet, little is known whether D1 or D2 receptor-mediated
      signals in the nucleus accumbens core (AcbC) are required to learn a reversal of
      the predictive significance of cues. OBJECTIVE: Here we examined the effects of a
      selective D1 or D2 receptor blockade in the AcbC on learning a reversal of
      previously acquired cue-reward magnitude contingencies. MATERIALS AND METHODS:
      Rats were trained on a reaction time (RT) task demanding conditioned lever
      release with discriminative visual cues signalling in advance the upcoming reward
      magnitude (one or five food pellets). After acquisition, RTs were guided by cue
      associated reward magnitudes, i.e. RTs of responses were significantly shorter
      for expected high vs low reward. Thereafter, cue-reward magnitude contingencies
      were reversed. Reversal learning was tested for 12 daily sessions with intra-AcbC
      micro-infusions being given on sessions 1-6. Subjects received pre-trial
      infusions of the selective D1 or D2 receptor antagonists, SCH23390 (0.5, 2 microg
      per side) or raclopride (1, 4 microg per side), or vehicle (0.5 microl). RESULTS:
      Intra-AcbC infusion of SCH23390 (0.5, 2 microg) or raclopride (1, 4 microg) did
      not inhibit discrimination reversal learning, but the higher dose of each drug
      increased RTs of instrumental responses. CONCLUSIONS: In a visual discrimination
      task as used here, D1 and D2 receptor-mediated signals in the AcbC seem to be
      unnecessary in updating the reward-predictive significance of cues, rather, they
      serve to activate instrumental behaviour.

PMID- 17021927
TI  - Standardize and compare contrast-enhanced ultrasonographic digital images
      obtained with different technologies: how to overcome the subjectivity.
AB  - OBJECTIVE: This study was conducted to compare digital images obtained with
      cadence contrast pulse sequencing (CPS) and coherent contrast imaging (CCI)
      technologies for contrast-enhanced ultrasonography (CEUS). METHODS: A CEUS study
      on 17 focal liver lesions was performed using CPS and CCI technologies with a
      second-generation contrast media. The lesion/liver ratio and conspicuity index
      were then calculated and compared with Adobe Photoshop 6.0. RESULTS: Lesion/liver
      ratio and conspicuity index using CCI ranged from 1.3 to 7.1 (mean value, 3) and
      19 to 127 (mean value, 58), respectively; by using CPS, we obtained results
      ranging from 2 to 19.1 (mean value, 8.9) and 57 to 164 (mean value, 109.2).
      Lesion/liver ratio and the conspicuity index for the lesions using CPS showed
      significantly (p < 0.0001) superior results than those obtained using CCI.
      CONCLUSION: The computed analysis with standardization allows an objective
      evaluation of digital images of CEUS. CPS technology resulted in better lesion
      conspicuity compared to CCI during CEUS study on focal liver lesions.

PMID- 17021928
TI  - Relaxed selection among duplicate floral regulatory genes in Lamiales.
AB  - Polyploidization is a prevalent mode of genome diversification within plants.
      Most gene duplicates arising from polyploidization (paralogs) are typically lost,
      although a subset may be maintained under selection due to dosage, partitioning
      of gene function, or acquisition of novel functions. Because they experience
      selection in the presence of other duplicate loci across the genome, interactions
      among genes may also play a significant role in the maintenance of paralogs
      resulting from polyploidization. Previously, we identified duplicates of the
      genes LFY/FLO and AP3/DEF that directly interact in a floral regulatory pathway
      and are thought to be the result of ancient polyploidization in the Lamiales (>
      50 mya). Although duplicates of MADS box genes including AP3/DEF are common
      throughout the angiosperm lineage, LFY/FLO duplicates in Lamiales are the first
      reported outside of tetraploid taxa. In order to explore hypotheses for the joint
      preservation of these interacting floral regulatory genes including novel LFY/FLO
      paralogs, here we clone FLO and DEF duplicates from additional Lamiales taxa and
      apply codon substitution models to test how selection acts on both genes
      following duplication. We find acceleration in the ratio of nonsynonymous-to
      synonymous nucleotide substitutions for one (FLO) or both (DEF) paralogs that
      appears to be due to relaxed purifying selection as opposed to positive selection
      and shows a different pattern among functional domains of these genes. Several
      mechanisms are discussed that might be responsible for preservation of co
      orthologs of FLO and DEF in Lamiales, including interactions among the genes of
      this regulatory pathway.

PMID- 17021929
TI  - Protein superfamily evolution and the last universal common ancestor (LUCA).
AB  - By exploiting three-dimensional structure comparison, which is more sensitive
      than conventional sequence-based methods for detecting remote homology, we have
      identified a set of 140 ancestral protein domains using very restrictive criteria
      to minimize the potential error introduced by horizontal gene transfer. These
      domains are highly likely to have been present in the Last Universal Common
      Ancestor (LUCA) based on their universality in almost all of 114 completed
      prokaryotic (Bacteria and Archaea) and eukaryotic genomes. Functional analysis of
      these ancestral domains reveals a genetically complex LUCA with practically all
      the essential functional systems present in extant organisms, supporting the
      theory that life achieved its modern cellular status much before the main kingdom
      separation (Doolittle 2000). In addition, we have calculated different
      estimations of the genetic and functional versatility of all the superfamilies
      and functional groups in the prokaryote subsample. These estimations reveal that
      some ancestral superfamilies have been more versatile than others during
      evolution allowing more genetic and functional variation. Furthermore, the
      differences in genetic versatility between protein families are more attributable
      to their functional nature rather than the time that they have been evolving.
      These differences in tolerance to mutation suggest that some protein families
      have eroded their phylogenetic signal faster than others, hiding in many cases,
      their ancestral origin and suggesting that the calculation of 140 ancestral
      domains is probably an underestimate.

PMID- 17021930
TI  - Proteasome-related HslU and HslV genes typical of eubacteria are widespread in
      eukaryotes.
AB  - Many eubacteria contain an ATP-dependent protease complex, which is built by
      multiple copies of the HslV and HslU proteins and is therefore called HslVU. HslU
      proteins are AAA + ATPases, while HslV proteins are proteases that show highly
      significant similarity to beta subunits of proteasomes. Therefore, the HslVU
      complex has been envisaged as a precursor or ancestral type of proteasome. Here
      we show that species of most of the main eukaryotic lineages have HslU and HslV
      genes very similar to those found in proteobacteria. We have detected them in
      amoebozoa, plantae, chromoalveolata, rhizaria, and excavata species. Phylogenetic
      analyses suggest that these genes have been obtained by endosymbiosis from the
      proteobacterial ancestor that gave rise to eukaryotic mitochondria. The products
      encoded by these eukaryotic genes adopt, according to modeling based on the known
      crystal structures of prokaryotic HslU and HslV proteins, conformations that are
      compatible with their being fully active, suggesting that functional HslVU
      complexes may be present in many eukaryotic species.

PMID- 17021931
TI  - Distance-based genome rearrangement phylogeny.
AB  - Evolution operates on whole genomes through direct rearrangements of genes, such
      as inversions, transpositions, and inverted transpositions, as well as through
      operations, such as duplications, losses, and transfers, that also affect the
      gene content of the genomes. Because these events are rare relative to nucleotide
      substitutions, gene order data offer the possibility of resolving ancient
      branches in the tree of life; the combination of gene order data with sequence
      data also has the potential to provide more robust phylogenetic reconstructions,
      since each can elucidate evolution at different time scales. Distance corrections
      greatly improve the accuracy of phylogeny reconstructions from DNA sequences,
      enabling distance-based methods to approach the accuracy of the more elaborate
      methods based on parsimony or likelihood at a fraction of the computational cost.
      This paper focuses on developing distance correction methods for phylogeny
      reconstruction from whole genomes. The main question we investigate is how to
      estimate evolutionary histories from whole genomes with equal gene content, and
      we present a technique, the empirically derived estimator (EDE), that we have
      developed for this purpose. We study the use of EDE on whole genomes with
      identical gene content, and we explore the accuracy of phylogenies inferred using
      EDE with the neighbor joining and minimum evolution methods under a wide range of
      model conditions. Our study shows that tree reconstruction under these two
      methods is much more accurate when based on EDE distances than when based on
      other distances previously suggested for whole genomes.

PMID- 17021932
TI  - Evolutionary conservation of protein backbone flexibility.
AB  - Internal protein dynamics is essential for biological function. During evolution,
      protein divergence is functionally constrained: properties more relevant for
      function vary more slowly than less important properties. Thus, if protein
      dynamics is relevant for function, it should be evolutionary conserved. In
      contrast with the well-studied evolution of protein structure, the evolutionary
      divergence of protein dynamics has not been addressed systematically before,
      apart from a few case studies. X-Ray diffraction analysis gives information not
      only on protein structure but also on B-factors, which characterize the
      flexibility that results from protein dynamics. Here we study the evolutionary
      divergence of protein backbone dynamics by comparing the C(alpha) flexibility (B
      factor) profiles for a large dataset of homologous proteins classified into
      families and superfamilies. We show that C(alpha) flexibility profiles diverge
      slowly, so that they are conserved at family and superfamily levels, even for
      pairs of proteins with nonsignificant sequence similarity. We also analyze and
      discuss the correlations among the divergences of flexibility, sequence, and
      structure.

PMID- 17021933
TI  - What is a 'novel' mtDNA mutation--and does 'novelty' really matter?
AB  - The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled by
      the seeming novelty of mutations that are either nonsynonymous or affect the
      protein synthesis machinery in patients. In order to determine the novelty of a
      detected mutation, the working geneticist nearly always consults MITOMAP--often
      exclusively. By reanalyzing some case studies of refractory anemia with ring
      sideroblasts, prostate cancer, and hearing impairment, we demonstrate that the
      practice of solely relying on MITOMAP can be most misleading. A notorious example
      is the T1243C mutation, which was assessed to be novel and deemed to be
      associated with some (rare) disease simply because researchers did not realize
      that T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majority
      of 'novel' mutations suspected of being pathogenic are in actual fact known (and
      presumably neutral) polymorphisms (although unknown to MITOMAP), and this becomes
      glaringly evident when proper database searches and straightforward Internet
      queries are carried out.

PMID- 17021934
TI  - Role of microtubules in tip growth of fungi.
AB  - Polarized cell growth is observed ubiquitously in all living organisms. Tip
      growth of filamentous fungi serves as a typical model for polar growth. It is
      well known that the actin cytoskeleton plays a central role in cellular growth.
      In contrast, the role of microtubules in polar growth of fungal tip cells has not
      been critically addressed. Our recent study, using a green fluorescent protein
      (GFP)-labeled tubulin-expressing strain of the filamentous fungus Aspergillus
      nidulans and treatment with an anti-microtubule reagent, revealed that
      microtubules are essential for rapid hyphal growth. Our results indicated that
      microtubule organization contributes to continuous tip growth throughout the cell
      cycle, which in turn enables the maintenance of an appropriate mass of cytoplasm
      for the multinucleate system. In filamentous fungi, the microtubule is an
      essential component of the tip growth machinery that enables continuous and rapid
      growth. Recent research developments are starting to elucidate the components of
      the tip growth machinery and their functions in many organisms. This recent
      knowledge, in turn, is starting to enhance the importance of fungal systems as
      simple model systems to understand the polar growth of cells.

PMID- 17021935
TI  - Cd-induced growth reduction in the halophyte Sesuvium portulacastrum is
      significantly improved by NaCl.
AB  - The effects of Cd(2+) and NaCl, applied together or separately, on growth and
      uptake of Cd(2+) were determined for the halophyte Sesuvium portulacastrum L.
      Seedlings were cultivated in the presence of 50 or 100 micromol L(-1) Cd(2+)
      alone or combined with 100 or 400 mmol L(-1) NaCl. Data showed that alone, Cd(2+)
      induced chlorosis, necrosis, and inhibited growth. Addition of NaCl to Cd(2+)
      containing medium restored growth and alleviated the toxicity, however. NaCl also
      enhanced the amounts of Cd(2+) accumulated in the shoots. All Cd(2+) treatment
      reduced K(+) and Ca(2+) uptake and transport to the shoots. Accumulation of Na(+)
      in the shoots was not affected by Cd(2+), however. Thus S. portulacastrum
      maintained its halophytic characteristics in the presence of Cd(2+). We suggest
      this halophyte could be used for phytoextraction of Cd(2+) from salt-contaminated
      sites.

PMID- 17021936
TI  - Developmental morphology of branching flowers in Nymphaea prolifera.
AB  - Nymphaea and Nuphar (Nymphaeaceae) share an extra-axillary mode of floral
      inception in the shoot apical meristem (SAM). Some leaf sites along the
      ontogenetic spiral are occupied by floral primordia lacking a subtending bract.
      This pattern of flower initiation in leaf sites is repeated inside branching
      flowers of Nymphaea prolifera (Central and South America). Instead of fertile
      flowers this species usually produces sterile tuberiferous flowers that act as
      vegetative propagules. N. prolifera changes the meristem identity from
      reproductive to vegetative or vice versa repeatedly. Each branching flower first
      produces some perianth-like leaves, then it switches back to the vegetative
      meristem identity of the SAM with the formation of foliage leaves and another set
      of branching flowers. This process is repeated up to three times giving rise to
      more than 100 vegetative propagules. The developmental morphology of the
      branching flowers of N. prolifera is described using both microtome sections and
      scanning electron microscopy.

PMID- 17021937
TI  - Streptomyces gulbargensis sp. nov., isolated from soil in Karnataka, India.
AB  - During the course of screening for industrially important microorganisms, an
      alkali-tolerant and thermotolerant actinomycete, strain DAS 131T, was isolated
      from a soil sample collected from the Gulbarga region, Karnataka province, India.
      The strain was characterized by a polyphasic approach that showed that it
      belonged to the genus Streptomyces. Growth was observed over a wide pH range (pH
      6-12) and at 45 degrees C. The 16S rRNA gene sequence of strain DAS 131T was
      deposited in the GenBank database under the accession number DQ317411. 16S rRNA
      gene sequence analysis revealed that strain DAS 131T was most closely related to
      Streptomyces venezuelae ISP 5230T (AY999739) with a sequence similarity of 99.5%
      (8 nucleotide differences out of 1,477). Despite this very high sequence
      similarity, strain DAS 131T was phenetically distinct from S. venezuelae. The DNA
      relatedness between these strains was 54%, indicating that strain DAS 131T is a
      distinct genomic species. On the basis of phenetic and genetic analyses, strain
      DAS 131T is classified as a new species in the genus Streptomyces, for which we
      propose the name Streptomyces gulbargensis sp. nov.

PMID- 17021938
TI  - Protein expression in Escherichia coli S17-1 biofilms: impact of indole.
AB  - Bacteria undergo significant changes during adherence to surfaces and biofilm
      development. Cell-to-cell signalling molecules are known to be involved in these
      phenotypic adaptations to the sessile mode of life. We demonstrated previously
      that indole can act as an extracellular signal to regulate biofilm formation in
      E. coli. To identify proteins over- or under-expressed in response to E. coli
      biofilm formation and indole signalling, we compared the proteomes of the E. coli
      S17-1 wild-type and 3714 (S17-1 tnaA::Tn5) tryptophanase-negative mutant cells
      (which don't produce indole) grown as suspensions or biofilms in the presence or
      absence of exogenous indole. From computer-assisted image analysis, 407 spots
      were discriminated on two-dimensional electropherograms. Principal component
      analysis (PCA) of the electropherograms did not discriminate between the
      proteomes of the wild-type and mutant cells grown as suspensions indicating that
      indole has a limited impact onto protein expression of planktonic cells. The
      first principal component extracted by PCA, after standardization of the
      observations, opposed planktonic and biofilm cells confirming the existence of
      changes in protein expression during E. coli biofilm formation. Among proteins
      over- or under-expressed by both sessile wild-type and mutant cells, we
      identified metabolic enzymes, transporters, proteins involved in the translation
      and transcription machinery, stress response and regulation, and signalling
      proteins. The wild-type and mutant strains grown as biofilms in the presence of
      indole were discriminated by the second component. The role of some proteins
      whose expression was altered in biofilm bacteria compared to suspended
      counterparts is discussed.

PMID- 17021939
TI  - Viability and physiological state transitions of Rhizopus oligosporus
      sporangiospores in tempe starter culture.
AB  - The viability and various physiological characteristics of individual
      sporangiospores of Rhizopus oligosporus in tempe starter cultures that had been
      stored for 8, 10, 16 and 30 months were examined by flow cytometry in combination
      with fluorescent dyes. Besides live, dead, and dormant spores we distinguished a
      category of sublethally damaged spores. Results indicated that the shelf-life of
      tempe starters was not limited by the death of spores, but by sublethal damage to
      spores as well as by dormancy which can be overcome by resuscitation, respiratory
      activation. During storage, the number of dormant and sublethally damaged spores
      increased: the longer the starter cultures were stored, the less dormant spores
      could still be activated. In contrast, the transition from sublethally damaged
      (spores that are not able to transform cFDA and emit green fluorescence except by
      activation treatment) to activated spores did not decrease with longer storage.
      However, after very long (30 months) storage, sublethally damaged spores could
      still be activated but could not germinate anymore. The shelf-life of spores in
      tempe starter is related to the physiological state of spores being sublethally
      damaged; a mechanism of physiological state transitions of R. oligosporus
      sporangiospores is proposed.

PMID- 17021940
TI  - "Microbiology is my hobby"--a short biography of Prof. J. Gijs Kuenen, Professor
      of Microbiology in Delft.

PMID- 17021942
TI  - Spontaneous aortic dissection limited to sinus of Valsalva and involving the left
      main coronary artery.
AB  - Aortic dissection limited to one sinus of Valsalva has been described exclusively
      as an iatrogenic complication during catheterization interventions. This life
      threatening subtype had a very small area of dissection, when coronary ostia are
      frequently involved. We report a 43-year-old man with dissection limited to left
      sinus of Valsalva, involving the left main coronary artery and causing non-ST
      myocardial infarction, including severe reversible ST-depression, maximum of 9 mm
      in V5 lead. Dissection was suggested by cineangiography, transesophageal
      echocardiogram, and contrast-enhanced multidetector computed tomography. Surgical
      treatment was successful. There were not any associated diseases in the sinuses
      of Valsalsa, aortic valve or coronary arteries. Unlike previous reported cases of
      aortic dissection with such limited localization, the present case was
      spontaneous, and not iatrogenic.

PMID- 17021941
TI  - Wheat Dof transcription factor WPBF interacts with TaQM and activates
      transcription of an alpha-gliadin gene during wheat seed development.
AB  - Wheat prolamin-box binding factor (WPBF), a DOF transcription factor previously
      was isolated from wheat endosperm and suggested to function as an activator of
      prolamin gene expression during seed development. In this study, we showed that
      WPBF is expressed in all wheat tissues analyzed, and a protein, TaQM, was
      identified from a wheat root cDNA library, to interact with the Dof domain of
      WPBF. The specific interaction between WPBF and TaQM was confirmed by pull-down
      assay and bimolecular fluorescence complementation (BiFC) experiment. The
      expression patterns of TaQM gene are similar with that of WPBF. The GST-WPBF
      expressed in bacteria binds the Prolamin box (PB) 5'-TGTAAAG-3', derived from the
      promoter region of a native alpha-gliadin gene encoding a storage protein.
      Transient expression experiments in co-transfected BY-2 protoplast cells
      demonstrated that WPBF trans-activated transcription from native alpha-gliadin
      promoter through binding to the intact PB. When WPBF and TaQM are co-transfected
      together the transcription activity of alpha-gliadin gene was six-fold higher
      than when WPBF was transfected alone. Furthermore, the promoter activities of
      WPBF gene were observed in the seeds and the vascular system of transgenic
      Arabidopsis, which was identical to the expression profiles of WPBF in wheat.
      Hence, we proposed that WPBF functions not only during wheat seed development but
      also during other growth and development processes.

PMID- 17021943
TI  - NMR solution structure of the acylphosphatase from Escherichia coli.
AB  - The solution structure of Escherichia coli acylphosphatase (E. coli AcP), a small
      enzyme catalyzing the hydrolysis of acylphosphates, was determined by (1)H and
      (15)N NMR and restrained modelling calculation. In analogy with the other members
      of AcP family, E. coli AcP shows an alpha/beta sandwich domain composed of four
      antiparallel and one parallel beta-strand, assembled in a five-stranded beta
      sheet facing two antiparallel alpha-helices. The pairwise RMSD values calculated
      for the backbone atoms of E. coli and Sulfolobus solfataricus AcP, Bovine common
      type AcP and Horse muscle AcP are 2.18, 5.31 and 5.12 A, respectively. No
      significant differences are present in the active site region and the catalytic
      residue side chains are consistently positioned in the structures.

PMID- 17021944
TI  - The spinal curvature irregularity index independently identifies vertebral
      fractures.
AB  - INTRODUCTION AND HYPOTHESIS: The spinal curvature irregularity index (SCII) is a
      quantitative measure of the irregularity of the spinal curvature. We evaluated
      the predictive ability of SCII to identify subjects with vertebral fractures
      (VF). METHODS: Vertebral heights were measured by quantitative vertebral
      morphometry in 461 Lebanese women 20-89 years of age and VFs were ascertained by
      the grade 1 Eastell method. SCII scores were log-transformed and expressed as Z
      SCII, the number of standard deviations above or below the mean ln(SCII) of young
      patients without VF. Univariate and multivariate binary logistic regression
      models were used to identify clinical predictors of VF. RESULTS: Women with a
      higher SCII were more likely to have prevalent VF. A higher SCII was associated
      with a greater prevalence of VF within each category of femoral neck BMD (normal,
      osteopenia, osteoporosis). In univariate analysis, predictors of VF included Z
      SCII (odds ratio, OR: 2.21, 95% CI: 1.80-2.71) and femoral neck T-score (OR:
      1.35, 95% CI: 1.12-1.63). In multivariate analysis, predictors of VF were: Z-SCII
      (OR: 1.54, 95% CI: 1.02-2.32), femoral neck T-score (OR: 1.41, 95% CI: 1.11-1.78)
      and age(3) (OR: 1.40, 95% CI 1.10-1.82). At a cutoff SCII of 9.5%, the
      sensitivity and specificity of SCII for VF were 71 and 64% respectively, and
      higher SCII cutoffs identified VFs with greater specificity. CONCLUSION: The SCII
      is a robust, simple and independent indicator of the presence of VFs.

PMID- 17021945
TI  - Compliance with osteoporosis drug therapy and risk of fracture.
AB  - INTRODUCTION: Patient compliance with osteoporosis drug therapy is often poor in
      clinical practice and may be associated with higher risk of fracture. METHODS: A
      nested case-control study was undertaken using a US health insurance claims
      database. The source population included all women aged >or=45 years who began
      drug therapy for osteoporosis. Cases consisted of those who experienced an
      osteoporosis-related fracture; they were matched to controls without osteoporosis
      related fracture. Compliance with osteoporosis drug treatment was assessed in
      terms of the number of therapy-days received and medication possession ratio
      (MPR). Conditional logistic regression was employed to examine the relationship
      between compliance and fracture risk. RESULTS: A total of 453 women with
      osteoporosis-related fracture were identified and matched to 2,160 controls.
      Fracture risk was significantly lower for patients with >180 days of therapy [181
      360 days: odds ratio (OR) = 0.70, 95% CI = 0.49-0.99; >360 days: OR = 0.65, 95%
      CI = 0.43-0.99) versus those with <or=30 days. Risk was also lower for patients
      with MPR >or=90% (OR = 0.70, 95% CI = 0.52-0.93) versus those with MPR <30%.
      Fracture risk decreased as compliance increased (p(trend) < 0.05). CONCLUSION:
      Among women initiating drug therapy for osteoporosis, better compliance is
      associated with reduced risk of fracture.

PMID- 17021947
TI  - Anatomical pitfalls in the technique for total extra peritoneal laparoscopic
      repair for inguinal hernias.
AB  - PURPOSE: The totally extraperitoneal laparoscopic approach for the treatment of
      inguinal hernia is a well-recognized technique with proven efficacy, low failure
      rate, and reduced post-operative pain. This laparoscopic technique is reputed to
      be a more difficult procedure to learn and practice than a laparoscopic trans
      abdomino-pre-peritoneal procedure: we hope this is because many surgeons don't
      well know extra-peritoneal anatomy of groin. So we proposed a "step by step"
      anatomical analysis, with pitfalls to avoid, of a totally extraperitoneal
      laparoscopic approach for treatment of inguinal hernia. METHODS: Our experience
      with totally extraperitoneal laparoscopic inguinal hernia repair with regard to
      the morphology of the inguinal-femoral region concerns 23 cadaver dissection and
      more than 400 surgical procedures, now permits clarification of a surgical
      technique that has hitherto not been well known. CONCLUSION: Photographic
      representations of surgical views are displayed, and detailed descriptions
      applicable to anatomical structures are presented.

PMID- 17021946
TI  - COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in
      Spanish postmenopausal women.
AB  - INTRODUCTION AND HYPOTHESIS: Genetic studies of osteoporosis have focused on
      analysing single polymorphisms in individual genes - with inconclusive results.
      An alternative approach may involve haplotypes and gene-gene interactions. The
      aim of the study was to test the association between the COL1A1, ESR1, VDR and
      TGFB1 polymorphisms or haplotypes and bone mineral density (BMD) in Spanish
      postmenopausal women. METHODS: Sixteen polymorphisms were analysed in 719
      postmenopausal women. ANOVA, ANCOVA and Xi2 tests were used to perform the
      statistical analysis. RESULTS: COL1A1 -1997G > T (p=0.04) and TGFB1 Leu10Pro
      (p=0.02) were found to be associated with adjusted lumbar spine (LS) BMD.
      Interactions were observed between: the COL1A1 -1997 G/T and Sp1 polymorphisms (p
      < 0.01 for LS BMD) and the COL1A1 -1663 indelT and VDR ApaI polymorphisms (p <
      0.01 for femoral neck (FN) BMD). The COL1A1 GDs and ESR1 LPX haplotypes were
      associated with FN BMD (p=0.03 and p=0.03). CONCLUSIONS: Polymorphisms at COL1A1
      and TGFB1 and haplotypes at COL1A1 and ESR1 were found to be associated with BMD
      in a cohort of postmenopausal Spanish women. Moreover, COL1A1 polymorphisms
      showed significant interactions among them and with the VDR 3' polymorphisms.

PMID- 17021948
TI  - Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse
      model of amyotrophic lateral sclerosis.
AB  - The purpose of this study is to evaluate neuroprotective effects of (-)
      Epigallocatechin-3-gallate (EGCG) in a transgenic mouse model of Amyotrophic
      lateral sclerosis (ALS). SOD1-G93A transgenic mice and wild-type mice were
      randomly divided into EGCG-treated groups (10 mg/kg, p.o) and vehicle-treated
      control groups. Rotarod measurement was performed to assess the motor function of
      mice starting at the age of 70 days. Nissl staining to examine the number of
      motor neurons and CD11b immunohistochemical staining to evaluate activation of
      microglia in the lumbar spinal cords were conducted at the age of 120 days. In
      addition, for further observation of regulation of cell signaling pathways by
      EGCG, we used immunohistochemical analysis for nuclear factor kappa B (NF-kappaB)
      and cleaved caspase-3 as well as western blot analysis to determine the
      expression of nitric oxide synthase (iNOS) and NF-kappaB in the spinal cord. This
      study demonstrated that oral administration of EGCG beginning from a pre
      symptomatic stage significantly delayed the onset of disease, and extended life
      span. Furthermore, EGCG-treated transgenic mice showed increased number of motor
      neurons, diminished microglial activation, reduced immunohistochemical reaction
      of NF-kappaB and cleaved caspase-3 as well as reduced protein level of iNOS and
      NF-kappaB in the spinal cords. In conclusion, this study provides further
      evidences that EGCG has multifunctional therapeutic effects in the mouse model of
      ALS.

PMID- 17021949
TI  - Complex glutamate labeling from [U-13C]glucose or [U-13C]lactate in co-cultures
      of cerebellar neurons and astrocytes.
AB  - Glutamate metabolism was studied in co-cultures of mouse cerebellar neurons
      (predominantly glutamatergic) and astrocytes. One set of cultures was superfused
      (90 min) in the presence of either [U-(13)C]glucose (2.5 mM) and lactate (1 mM)
      or [U-(13)C]lactate (1 mM) and glucose (2.5 mM). Other sets of cultures were
      incubated in medium containing [U-(13)C]lactate (1 mM) and glucose (2.5 mM) for 4
      h. Regardless of the experimental conditions cell extracts were analyzed using
      mass spectrometry and nuclear magnetic resonance spectroscopy. (13)C labeling of
      glutamate was much higher than that of glutamine under all experimental
      conditions indicating that acetyl-CoA from both lactate and glucose was
      preferentially metabolized in the neurons. Aspartate labeling was similar to that
      of glutamate, especially when [U-(13)C]glucose was the substrate. Labeling of
      glutamate, aspartate and glutamine was lower in the cells incubated with [U
      (13)C]lactate. The first part of the pyruvate recycling pathway, pyruvate
      formation, was detected in singlet and doublet labeling of alanine under all
      experimental conditions. However, full recycling, detectable in singlet labeling
      of glutamate in the C-4 position was only quantifiable in the superfused cells
      both from [U-(13)C]glucose and [U-(13)C]lactate. Lactate and alanine were mostly
      uniformly labeled and labeling of alanine was the same regardless of the labeled
      substrate present and higher than that of lactate when superfused in the presence
      of [U-(13)C]glucose. These results show that metabolism of pyruvate, the
      precursor for lactate, alanine and acetyl-CoA is highly compartmentalized.

PMID- 17021950
TI  - Cell type specific signalling by hematopoietic growth factors in neural cells.
AB  - Correct timing and spatial location of growth factor expression is critical for
      undisturbed brain development and functioning. In terminally differentiated cells
      distinct biological responses to growth factors may depend on cell type specific
      activation of signalling cascades. We show that the hematopoietic growth factors
      thrombopoietin (TPO) and granulocyte colony-stimulating factor (GCSF) exert cell
      type specific effects on survival, proliferation and the degree of
      phosphorylation of Akt1, ERK1/2 and STAT3 in rat hippocampal neurons and cortical
      astrocytes. In neurons, TPO induced cell death and selectively activated ERK1/2.
      GCSF protected neurons from TPO- and hypoxia-induced cell death via selective
      activation of Akt1. In astrocytes, neither TPO nor GCSF had any effect on cell
      viability but inhibited proliferation. This effect was accompanied by activation
      of ERK1/2 and inhibition of STAT3 activity. A balance between growth factors,
      their receptors and signalling proteins may play an important role in regulation
      of neural cell survival.

PMID- 17021951
TI  - Marginal regression models with a time to event outcome and discrete multiple
      source predictors.
AB  - Information from multiple informants is frequently used to assess
      psychopathology. We consider marginal regression models with multiple informants
      as discrete predictors and a time to event outcome. We fit these models to data
      from the Stirling County Study; specifically, the models predict mortality from
      self report of psychiatric disorders and also predict mortality from physician
      report of psychiatric disorders. Previously, Horton et al. found little
      relationship between self and physician reports of psychopathology, but that the
      relationship of self report of psychopathology with mortality was similar to that
      of physician report of psychopathology with mortality. Generalized estimating
      equations (GEE) have been used to fit marginal models with multiple informant
      covariates; here we develop a maximum likelihood (ML) approach and show how it
      relates to the GEE approach. In a simple setting using a saturated model, the ML
      approach can be constructed to provide estimates that match those found using
      GEE. We extend the ML technique to consider multiple informant predictors with
      missingness and compare the method to using inverse probability weighted (IPW)
      GEE. Our simulation study illustrates that IPW GEE loses little efficiency
      compared with ML in the presence of monotone missingness. Our example data has
      non-monotone missingness; in this case, ML offers a modest decrease in variance
      compared with IPW GEE, particularly for estimating covariates in the marginal
      models. In more general settings, e.g., categorical predictors and piecewise
      exponential models, the likelihood parameters from the ML technique do not have
      the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal
      models for its flexibility, ease of interpretation and comparable efficiency to
      ML in the presence of missing data.

PMID- 17021952
TI  - Case managers' experiences of personal growth: learning from consumers.
AB  - This study examines aspects of case managers' perceived personal growth in their
      work with consumers. Using a sample of 98 case managers, the psychometric
      properties of a brief self-report measure of personal growth of case managers
      were examined. The Case Manager Personal Growth Scale (CMPG) showed good
      reliability and construct validity as evidenced by negative correlations with
      scores on professional burnout and positive correlations with personal
      accomplishment and job satisfaction scores. CMPG scores were unrelated to social
      desirability scores or caseload size and positively related to age and tenure in
      the mental health system. Results suggest the strong relevance of the construct
      of personal growth for case managers.

PMID- 17021953
TI  - Are the Health of the Nation Outcome Scales a valid and practical instrument to
      measure outcomes in North America? A three-site evaluation across Nova Scotia.
AB  - We tested the usability, sensitivity and validity of the Health of the Nation
      Outcome Scales (HoNOS) in routine clinical practice in North America. Three pilot
      sites provided ratings on all inpatient and outpatient referrals over 4 months
      using versions covering children and adolescents (HoNOSCA), working-age adults
      and the over-65s. Data were entered using the routine administrative data system.
      Sixty-one percent of eligible patients had at least one HoNOS rating (n = 485).
      Following the initial rating, subsequent completion rates reached 80%. Ratings
      were sensitive to time and setting, with significantly higher scores in
      inpatients than outpatients. Individual diagnoses had different patterns of
      scores, further supporting validity.

PMID- 17021955
TI  - Lhermitte-Duclos disease.
AB  - A 46-year-old female patient with previously recognized Graves' ophthalmopathy,
      underwent total thyroidectomy. After thyroid surgery exophthalmos worsened and
      signs unsteadiness of gait appeared. Magnetic resonance imaging showed a lesion
      in the basal portion of the left cerebellar hemisphere. Therefore, the patient
      underwent surgery. Pathological examination revealed dysplastic gangliocytoma of
      the cerebellum (Lhermitte-Duclos disease).

PMID- 17021954
TI  - Postpartum stress as a predictor of women's minor psychiatric morbidity.
AB  - The purpose of this study was to predict women's minor psychiatric morbidity
      after they had childbirth as measured repeatedly at the first, the third, and the
      fifth weeks of the postpartum period. The Chinese Health Questionnaire, the
      Postpartum Stress Scale, the Zung's Self-rating Depression Scale and Anxiety
      Scale, and the Social Support Scale were used at the three points of time. A
      total of 526 women in Taiwan participated in the study. The results indicated
      that postpartum stress and anxiety are important predictors for postpartum
      women's minor psychiatric morbidity at three points in time.

PMID- 17021956
TI  - Factors relating to organizational commitment of older male employees in Japan.
AB  - Recently, an increasing number of employers have provided employment
      opportunities for older adults. Yet, few studies pay attention to older
      employees' perceptions of their employment. Using a Japanese national sample of
      995 male employees aged 55 to 64, this study examined whether the existing
      research on organizational commitment applies to older employees, whether
      measures that are unique to older employees have significant relationships to
      their organizational commitment, and whether the effects of these factors differ
      by retirement status. The results of hierarchical multiple regression analyses
      showed significant relationships between employee organizational commitment and
      employment security, personal relationships in workplaces and job
      characteristics. Negative ageism and employer-sponsored programs for older
      employees also had significant relationships to organizational commitment. The
      effects of salary, job autonomy, job demands, and employer-sponsored programs
      differed by retirement status. While the study was consistent with the existing
      research, it also suggested the importance of measures that are unique to older
      employees.

PMID- 17021957
TI  - Aging and health status of elderly in Latin America and the Caribbean:
      preliminary findings.
AB  - Aging in Latin America and the Caribbean will not proceed along known paths
      already followed by more developed countries. In particular, the health profile
      of the future elderly population is less predictable due to factors associated
      with their demographic past that may haunt them for a long time and make them
      more vulnerable, even if economic and institutional conditions turn out to be
      better than what they are likely to be. This paper answers a set of questions
      regarding the nature and determinants of health status among the elderly in Latin
      America and the Caribbean using SABE (Survey on Health and Well-Being of Elders),
      a cross-sectional representative sample of over 10,000 elderly aged 60 and above
      in private homes in seven major cities in Latin America and the Caribbean. We
      examine health outcomes such as self-reported health, functional limitations
      Activities of Daily Living (ADL's) and Instrumental Activities of Daily Living
      (IADL's), obesity (ratio of weight in kilograms to the square of height in
      centimeters), and self-reported chronic conditions (including diabetes). The
      findings include: (a) Countries differ in self-reported health but exhibit much
      less differences in terms of functional limitations. The number of chronic
      conditions increase with age and is higher among females than among males; (b) On
      average SABE countries display levels of self-reported diabetes (and obesity)
      that are as high if not higher than those found in the US; (c) There is evidence,
      albeit weaker than expected, suggesting deteriorated health and functional status
      in the region; (d) There is important evidence pointing toward rather strong
      inequalities (by education and income) in selected health outcomes. Preliminary
      findings from SABE confirm that Latin America and the Caribbean display
      peculiarities in the health profile of elderly, particularly with regard to
      diabetes and obesity. It is important that new policy initiatives begin to
      seriously target the region's elderly, especially with an emphasis on the
      prevention and treatment of diabetes and obesity.

PMID- 17021958
TI  - Profile information matrix for nonlinear transformation models.
AB  - For semiparametric models, interval estimation and hypothesis testing based on
      the information matrix for the full model is a challenge because of potentially
      unlimited dimension. Use of the profile information matrix for a small set of
      parameters of interest is an appealing alternative. Existing approaches for the
      estimation of the profile information matrix are either subject to the curse of
      dimensionality, or are ad-hoc and approximate and can be unstable and numerically
      inefficient. We propose a numerically stable and efficient algorithm that
      delivers an exact observed profile information matrix for regression coefficients
      for the class of Nonlinear Transformation Models [A. Tsodikov (2003) J R Statist
      Soc Ser B 65:759-774]. The algorithm deals with the curse of dimensionality and
      requires neither large matrix inverses nor explicit expressions for the profile
      surface.

PMID- 17021959
TI  - An alternative competing risk model to the Weibull distribution for modelling
      aging in lifetime data analysis.
AB  - A simple competing risk distribution as a possible alternative to the Weibull
      distribution in lifetime analysis is proposed. This distribution corresponds to
      the minimum between exponential and Weibull distributions. Our motivation is to
      take account of both accidental and aging failures in lifetime data analysis.
      First, the main characteristics of this distribution are presented. Then, the
      estimation of its parameters are considered through maximum likelihood and
      Bayesian inference. In particular, the existence of a unique consistent root of
      the likelihood equations is proved. Decision tests to choose between an
      exponential, Weibull and this competing risk distribution are presented. And this
      alternative model is compared to the Weibull model from numerical experiments on
      both real and simulated data sets, especially in an industrial context.

PMID- 17021960
TI  - A phase II study of bosentan, a dual endothelin receptor antagonist, as
      monotherapy in patients with stage IV metastatic melanoma.
AB  - There is no effective systemic therapy for disseminated metastatic melanoma. Data
      suggest that endothelin may play a role in pathophysiology of melanoma and that
      the dual endothelin receptor antagonist bosentan may have anti-tumor activity.
      This multicenter, open-label, single-arm, prospective, proof-of-concept study
      assessed the effects of bosentan monotherapy (500 mg oral tablets, bid) on tumor
      response in patients with stage IV metastatic melanoma. Patients were treated
      until disease progression, death or serious adverse event leading to premature
      study drug discontinuation. Tumor response was assessed at 6-weekly intervals
      using the Response Evaluation Criteria in Solid Tumors (RECIST). Among the 35
      patients included in this study with stage IV metastatic melanoma, 21 (60%) were
      stage M1C, 10 (29%) stage M1B and 4 (11%) stage M1A (American Joint Committee on
      Cancer [AJCC] classification). Nine patients (26%) had received prior therapy for
      stage IV melanoma. Disease stabilization was observed in 6 of the 32 patients
      analyzed per protocol at week 6 with confirmatory evaluation at week 12, 5 of
      whom were still stable at > or =24 weeks. Of the 6 patients with disease
      stabilization, 2 were stage M1A, 1 was stage M1B and the remaining 3 were stage
      M1C. Partial or complete response was not observed. Progressive disease was
      observed in 17 (49%) patients at week 12 and in 25 (71%) patients at the end of
      the study (data base closure). The most frequent adverse events were typical for
      the underlying disease or known to be associated with bosentan: headache (43%),
      fatigue (34%), nausea (31%), back pain (23%) and abnormal hepatic function (23%).
      Bosentan might have benefit in disease stabilization in certain patients with
      metastatic melanoma and deserves further investigation in combination with other
      anticancer drugs.

PMID- 17021961
TI  - Ecotoxicological assessment of effluents in the Basque country (Northern Spain)
      by acute and chronic toxicity tests using Daphnia magna straus.
AB  - Acute pass/fail, multi-concentration tests, and 3-brood chronic toxicity tests
      with Daphnia magna Straus (Cladocera, Crustacea) were used to characterise
      industrial and municipal effluents from various sources. The effluents that
      "passed" the pass/fail tests had 48-h EC50 values >100% and reproduction No
      Observed Effect Concentration (NOECs) > or =100%, except for one effluent that
      had a reproduction NOEC of 31.6%. The acute multi-concentration toxicity tests
      allowed a rapid classification of effluents from Very Toxic (48-h EC50 < 25%), to
      Non-Toxic (48-h EC50 >100%). The acute-to-chronic ratio (ACR: 48-h EC50 divided
      by the NOEC for reproduction) in the studied effluents ranged from 5 to about
      100. From these results, we propose a step-wise protocol for assessing effluent
      toxicity. First, effluent is evaluated by means of simple and rapid pass/fail
      acute toxicity tests, to discriminate Non-Toxic from potentially Toxic effluents,
      thus facilitating the establishment of priority actions. Second, 48-h ECx is
      estimated to classify effluents on a toxicity scale from Non-Toxic to Very Toxic.
      Third, chronic multi-concentration tests are used to calculate reproduction
      NOECs. These parameters combined with data on effluent chemical composition,
      chemical and hydrological characteristics of receiving waters, and biological
      quality criteria can be jointly used for more rational regulatory practices and
      risk assessment of effluents.

PMID- 17021962
TI  - Impact of adenoma size in distal colon on risk for advanced adenoma of the
      proximal colon.
AB  - Adenomas of the rectosigmoid colon are considered markers of risk for advanced
      adenomas of the proximal colon. However, studies report a wide variation in risk.
      This study was designed to determine the risk for advanced adenomas in the
      proximal colon in patients from a large, homogeneous population with an advanced
      or nonadvanced adenoma of the distal colon. We designed a prospective study of
      7157 patients who were evaluated for neoplasia by flexible sigmoidoscopy and,
      when adenomas were found, by colonoscopy. Adenomas were considered advanced if
      they were > or =10 mm in size or had villous or dysplastic features. Ninety-seven
      patients had an advanced adenoma of the distal colon (Group A) and were compared
      with 183 patients who had a nonadvanced adenoma (Group B). Seven patients (7.2%)
      in Group A had an advanced adenoma of the proximal colon, compared with four
      patients (2.2%) in Group B (P < 0.05, relative risk = 3.3). When patients with
      adenomas of the distal colon >5 mm (Group C) were compared to patients with
      adenomas < or =5 mm (Group D), the prevalence of advanced adenomas of the
      proximal colon remained at 7% (10/143) for Group C but fell to 0.73% (1/137) for
      Group D (P = 0.011, relative risk = 9.6). By expanding the criteria for risk from
      adenomas of the distal colon to include all adenomas >5 mm, the relative risk for
      advanced adenoma of the proximal colon was increased threefold.

PMID- 17021963
TI  - Analysis of amorphous and nanocrystalline solids from their X-ray diffraction
      patterns.
AB  - PURPOSE: The purpose of this paper is to provide a physical description of the
      amorphous state for pharmaceutical materials and to investigate the
      pharmaceutical implications. Techniques to elucidate structural differences in
      pharmaceutical solids exhibiting characteristic X-ray amorphous powder patterns
      are also presented. MATERIALS AND METHODS: The X-ray amorphous powder diffraction
      patterns of microcrystalline cellulose, indomethacin, and piroxicam were measured
      with laboratory XRPD instrumentation. Analysis of the data were carried out using
      a combination of direct methods, such as pair distribution functions (PDF), and
      indirect material modeling techniques including Rietveld, total scattering, and
      amorphous packing. RESULTS: The observation of X-ray amorphous powder patterns
      may indicate the presence of amorphous, glassy or disordered nanocrystalline
      material in the sample. Rietveld modeling of microcrystalline cellulose (Avicel
      PH102) indicates that it is predominantly disordered crystalline cellulose Form
      Ibeta with some amorphous contribution. The average crystallite size of the
      disordered nanocrystalline cellulose was determined to be 10.9 nm. Total
      scattering modeling of ground samples of alpha, gamma, and delta crystal forms of
      indomethacin in combination with analysis of the PDFs provided a quantitative
      picture of the local structure during various stages of grinding. For all three
      polymorphs, with increased grinding time, a two-phase system, consisting of
      amorphous and crystalline material, continually transformed to a completely
      random close packed (RCP) amorphous structure. The same pattern of transformation
      was detected for the Form I polymorph of piroxicam. However, grinding of Form II
      of piroxicam initially produced a disordered phase that maintained the local
      packing of Form II but over a very short nanometer length scale. The initial
      disordered phase is consistent with continuous random network (CRN) glass
      material. This initial disordered phase was maintained to a critical point when a
      transition to a completely amorphous RCP structure occurred. CONCLUSIONS:
      Treating X-ray amorphous powder patterns with different solid-state models,
      ranging from disordered nanocrystalline to glassy and amorphous, resulted in the
      assignment of structures in each of the systems examined. The pharmaceutical
      implications with respect to the stability of the solid are discussed.

PMID- 17021964
TI  - [MALT lymphoma of the lung: radiological diagnosis].

PMID- 17021974
TI  - [Recent trends in cardiovascular imaging as reflected in RoFo].

PMID- 17021975
TI  - [Mammography screening in Germany: how, when and why?].
AB  - It is well-known from several large randomized trials that regular mammography
      screening can reduce breast cancer mortality. While in many countries mammography
      screening programs have been in existence for quite some time, an organized
      population-based screening program is only now being implemented in Germany. In
      this review article, the different elements of a mammography screening program
      and their effect on the cost-benefit ratio are discussed and the planned German
      screening program is compared to the international programs.

PMID- 17021976
TI  - [Radiological diagnostics and follow-up of rectal carcinoma].
AB  - Rectal carcinoma is one of the most frequent malignant tumors in adulthood. Not
      only after total resection but also after partial resection of the tumor with
      postoperative radiochemotherapy a sufficient follow-up is necessary to diagnose
      recurrent rectal cancer as early as possible. Various guidelines suggest
      different intervals for physical examinations and diagnostic methods depending on
      the initial tumor stage. In addition to routine examinations, the physician can
      choose between CT, MRI, endosonography and functional imaging techniques such as
      PET and immunoscintigraphy for further evaluation if a recurrent rectal cancer is
      suspected. Multiple studies and meta-analyses show the differences in the
      specificity and sensitivity of the diagnostic methods in the detection of lymph
      nodes, metastases, and local tumor infiltration. Endosonography and endorectal
      MRI show very good results in staging local tumor infiltration. However,
      obstructive lesions can inhibit an adequate examination. CT provides prompt and
      convincing results in the evaluation of the metastases. Most of the time the
      tumor can be identified but the lack of detailed imaging makes it hard to perform
      sufficient staging. Additionally image-guided biopsy can be performed.
      Immunoscintigraphy and PET have a high specificity because they take advantage of
      the tumor's metabolism. The introduction of the PET-CT has eliminated the
      disadvantage of low image resolution. In addition to the detection of small
      nodular pulmonary metastases, MRI with its "phased-array" coils is another
      excellent tool for the diagnosis of recurrent rectal cancer and search for
      metastases. This review shows the advantages and disadvantages of each diagnostic
      method in the visualization of recurrent rectal cancer.

PMID- 17021977
TI  - [Clinical and histopathological results after local chemoembolization of oral and
      oropharyngeal carcinoma--comparison with intraarterial chemoperfusion].
AB  - PURPOSE: Retrospective analysis of clinical and histopathological results after
      neoadjuvant intraarterial chemoembolization (iaCE) as compared to intraarterial
      chemoperfusion (iaCP) in patients with oral and oropharyngeal squamous cell
      cancer (SCC). MATERIALS AND METHODS: 289 patients (mean age 60 years, 68 % male)
      with SCC of the oral cavity or the oropharynx (WHO stage I-IV) received (1)
      neoadjuvant iaCE (n = 103) with a crystalline suspension of cisplatin (150
      mg/m(2), solution ratio 5 mg cisplatin ad 1 ml NaCl 0.9 %, total volume 40 - 60
      ml) or (2) iaCP (n = 186) using high-dose cisplatin infusions (150 mg/m(2), 1 mg
      cisplatin ad 1 ml NaCl 0.9 %, 400 - 500 ml). The decision for iaCE or iaCP was
      made individually for each patient based on tumor localization and expected
      vascular supply. Four weeks after local chemotherapy, the treatment response was
      evaluated according (1) to WHO criteria and (2) to histopathological TNM-grading
      after tumor resection. RESULTS: The overall treatment response was 72.5 % after
      iaCE and 47 % after iaCP (p < 0.001). A stable disease was found in 24 % and 48
      %, respectively, and tumor progression was found in 3 % for both modalities.
      Histopathological examination of resected tumors revealed complete remission in
      20 % after iaCE and 13 % after iaCP. The percentage of complete remissions was
      highest in local T1 and T2 tumors after iaCE (42.9 versus 22.4 % after iaCP, p =
      0.031). Local side effects were significantly more frequent after iaCE than after
      iaCP (p < 0.001), especially in obese patients with extended carcinoma of the
      oral floor or the tongue base. CONCLUSION: Compared to iaCP, clinical and
      histopathological remission rates are significantly higher after iaCE, especially
      in early stages of local tumor growth. However, in view of the higher risk of
      regional complications, indication for iaCE should be considered cautiously and
      its application should be limited to small tumors of the oral floor and the oral
      tongue.

PMID- 17021978
TI  - [Quantification of pulmonary emphysema in multislice-CT using different software
      tools].
AB  - PURPOSE: The data records of thin-section MSCT of the lung with approx. 300
      images are difficult to use in manual evaluation. A computer-assisted pre
      diagnosis can help with reporting. Furthermore, post-processing techniques, for
      instance, for quantification of emphysema on the basis of three-dimensional
      anatomical information might be improved and the workflow might be further
      automated. MATERIALS AND METHODS: The results of 4 programs (Pulmo, Volume, YACTA
      and PulmoFUNC) for the quantitative analysis of emphysema (lung and emphysema
      volume, mean lung density and emphysema index) of 30 consecutive thin-section
      MSCT datasets with different emphysema severity levels were compared. The
      classification result of the YACTA program for different types of emphysema was
      also analyzed. RESULTS: Pulmo and Volume have a median operating time of 105 and
      59 minutes respectively due to the necessity for extensive manual correction of
      the lung segmentation. The programs PulmoFUNC and YACTA, which are automated to a
      large extent, have a median runtime of 26 and 16 minutes, respectively. The
      evaluation with Pulmo and Volume using 2 different datasets resulted in
      implausible values. PulmoFUNC crashed with 2 other datasets in a reproducible
      manner. Only with YACTA could all graphic datasets be evaluated. The lung volume,
      emphysema volume, emphysema index and mean lung density determined by YACTA and
      PulmoFUNC are significantly larger than the corresponding values of Volume and
      Pulmo (differences: Volume: 119 cm(3)/65 cm(3)/1 %/17 HU, Pulmo: 60 cm(3)/96
      cm(3)/1 %/37 HU). Classification of the emphysema type was in agreement with that
      of the radiologist in 26 panlobular cases, in 22 paraseptalen cases and in 15
      centrilobular emphysema cases. CONCLUSION: The substantial expenditure of time
      obstructs the employment of quantitative emphysema analysis in the clinical
      routine. The results of YACTA and PulmoFUNC are affected by the dedicated
      exclusion of the tracheobronchial system. These fully automatic tools enable not
      only fast quantification without manual interaction, but also a reproducible
      measurement without user dependence.

PMID- 17021979
TI  - [Acute pulmonary embolism: prediction of cor pulmonale and short-term patient
      survival from assessment of cardiac dimensions in routine multidetector-row CT].
AB  - PURPOSE: Evaluation of the prognostic value of morphological cardiac parameters
      in patients with suspected and incidental acute pulmonary embolism (PE) using
      multidetector-row chest CT (MSCT). MATERIALS AND METHODS: 2335 consecutive MSCT
      scans were evaluated for the presence of PE. The arterial enhancement and
      analysability of pulmonary arteries and the heart were assessed as parameters of
      the scan quality. The diastolic right and left ventricular short axes (RV (D), LV
      (D)) and the interventricular septal deviation (ISD) were measured in all PE
      positive patients and the echocardiography reports were reviewed. The clinical
      data assessment included cardio-respiratory and other co-morbidities, systemic
      anticoagulant therapy (ACT), and the 30-day outcome. Predictors of acute cor
      pulmonale and the short-term outcome were calculated by univariate and
      multivariate logistic regressions including odds ratios (OR) and ROC analyses
      using positive (PPV) and negative predictive values (NPV). RESULTS: 90 patients
      with acute PE were included (36 with clinically suspected PE, 54 with incidental
      PE). 26 patients had cardio-respiratory co-morbidities. Four patients underwent
      systemic thrombolysis, 43 underwent anticoagulation in therapeutic doses, 19
      underwent anticoagulation in prophylactic doses, and 24 patients did not undergo
      ACT. 15 of 41 patients had echocardiographic evidence of acute cor pulmonale. 8
      patients died within 30 days. The RV (D) was the best independent predictor of
      acute cor pulmonale (p = 0,002, OR = 9.16, PPV = 0.68, NPV = 1 at 4.49 cm cut
      off) and short-term outcome (p = 0,0005, OR = 2.82, PPV = 0.23, NPV = 0.98 at
      4.75 cm cut off). The RV (D)/LV (D) ratio had a PPV of 0.85 for cor pulmonale.
      CONCLUSION: The RV (D) and RV (D)/LV (D) ratio were suitable for identifying
      patients with acute cor pulmonale and for benign short-term prognosis. Further
      studies should prospectively address the combined use of CT-morphological and
      clinical parameters for the prediction of patient outcome.

PMID- 17021980
TI  - [Quantification of right ventricular function in congenital heart disease:
      correlation of 3D echocardiography and MRI as complementary methods].
AB  - PURPOSE: In congenital heart disease, the exact determination of the right
      ventricular function is of high importance for therapeutic and especially
      surgical planning. The aim of this study was to correlate the parameters of the
      right ventricular function in MRI and 3D echocardiography to determine the
      agreement of both modalities. MATERIALS AND METHODS: In 18 patients suffering
      from congenital heart disease, 3D echocardiography was performed using a Philips
      Sonos 7500 system. In MRI short axis slices with a 4-mm distance were acquired
      using an SSFP sequence on a Siemens Sonata or Symphony System. Volumetry for both
      modalities was performed on an external workstation (Tomtec) using the EchoView
      software. RESULTS: Enddiastolic and endsystolic volumes showed a highly
      significant correlation with coefficients of 0.996 and 0.990, respectively. In
      echocardiography there was a systematic slight underestimation of enddiastolic
      volumes and overestimation of endsystolic volumes. The Wilcoxon test did not show
      significant differences between the volumes and ejection fractions assessed by
      both modalities. CONCLUSION: There is an excellent correlation in the
      quantification of right ventricular volumes in MRI and 3D echocardiography, which
      allows a comparison of acquired volumes in clinical follow-up.

PMID- 17021981
TI  - [16-Row multidetector CT of the pelvis after iliosacrally inserted osteosynthetic
      screws: experimental study of dose adjustment on preserved human cadaver
      specimens].
AB  - PURPOSE: The study was performed to assess the necessity of dose adjustment (kV
      or mAs (eff.)) in 16-slice CT (MDCT) in postoperative controls of iliosacrally
      inserted osteosynthetic screws (OS) on preserved human cadaver specimens. The
      minimal tube settings for diagnostic imaging of the pelvic bone were analyzed and
      the effective doses and important organ doses were calculated. MATERIALS AND
      METHODS: 16 preserved human cadaver specimens with transiliac osteosynthetic
      screws were scanned on a 16-slice CT (collimation 16 x 0.75 mm, pitch 0.7) with
      10 different tube settings (35, 50, 75, 100, 150 mAs (eff.) and 120 and 140 kV).
      32 datasets (blinded for name and scan parameters) with and without OS were
      independently evaluated by four observers. The 10 series were sorted by
      subjective image quality (image noise, contours, artifacts), and the series with
      the lowest but still diagnostic quality was selected. The statistical analysis
      included multi-rater-kappa-test and Wilcoxon test for paired samples. RESULTS:
      The multi-reader agreements for sorting the series were fair (kappa = 0.38). The
      agreements in comparing the lowest diagnostic image qualities were slight to fair
      (kappa = 0.08-0.23). The paired sample test comparing the lowest diagnostic image
      quality with and without OS showed no statistical significance (p = 0.29). 87.5 %
      of the readouts (n = 64 [16 examinations, 4 readers]) with OS and 78.1 % of those
      without OS could be adequately diagnosed using the three series with the lowest
      effective doses (0.9-1.4 mSv for men, 1.4-2.0 mSv for women; 120 kV-35 mAs
      (eff.), 120-50, 140-35). CONCLUSION: MSCT scans of the pelvic bone can be
      performed with very low effective doses. It is not necessary to adjust tube
      settings when imaging bones with osteosynthetic screws. If the concept for the
      control of the pelvic osteosynthetic screw position includes more than 2
      conventional films (for example anterioposterior view with additional inlet and
      outlet views), a low dose CT is preferable to conventional radiography.

PMID- 17021982
TI  - [Increasing iron accumulation of the adenohypophysis in the framework of a
      hemochromatosis--characteristic depiction using magnetic resonance tomography].

PMID- 17021983
TI  - [Position paper of Bavarian radiologists on mammographic screening].

PMID- 17021987
TI  - [Screening for diabetes: yes! but how?].

PMID- 17021988
TI  - [Detection of a previously unrecognized type 2 diabetes using a risk
      questionnaire. Efficiency for general population screening].
AB  - BACKGROUND AND OBJECTIVE: The detection of unknown cases of diabetes mellitus is
      of great medical and public health interest. In the present study a stepwise
      screening procedure was used to examine the effectiveness of a diabetes-risk
      questionnaire at a population level. PATIENTS AND METHODS: 58,254 insured persons
      (34,179 men and 24,075 women (55 years and older) enrolled in the Health
      Insurance "Techniker Krankenkasse" of Thuringia and the Duesseldorf area were
      contacted per mail to participate. 21,218 returned the questionnaire. They were
      contacted again and encouraged to participate in a medical check-up for early
      detection of diabetes. RESULTS: Data of 4,314 individuals (20.3%) who
      participated in the medical check-up were analysed. Their fasting blood glucose
      was measured (FBG, n=3,888) and, if necessary, they underwent an additional oral
      glucose tolerance test (OGTT, n=2,048). In 192 cases (4.5%) the general
      practitioner (GP) diagnosed manifest diabetes mellitus. In an additional 393
      patients (9.1%) an impaired glucose tolerance was found. Analysis of documented
      blood glucose measurements suggested a manifest diabetes mellitus in 3.5% (by
      OGTT) and 10.3% (by FBG), as well as an impaired glucose tolerance in 16.1% (by
      OGTT) and 36.6% (by FBG). CONCLUSIONS: These results demonstrate good
      effectiveness of the screening procedure among the participants of a medical
      check-up programme for early detection of diabetes mellitus and its precursors.
      However, the effectiveness of population-based diabetes screening with only a
      mailing of a risk questionnaire was unsatisfactory.

PMID- 17021989
TI  - [A 56-year-old female patient with Raynaud's syndrome, increased liver enzymes
      and neuropsychiatric symptoms].
AB  - CASE HISTORY: A 56-year-old woman presented with increased liver enzymes (GPT,
      GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration.
      FINDINGS AND DIAGNOSIS: Serology and liver biopsy indicated chronic hepatitis C
      infection (HCV) and viral-induced liver cirrhosis with unremarkable liver
      synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high
      elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical
      serological parameters of mixed tissue collagenous (Sharp}s disease), were
      detectable. Magnetic resonance spectroscopy (H-MRS) was performed to
      differentiate between cerebral vasculitis and mild hepatic encephalopathy. This
      detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is
      specific for HE. TREATMENT AND COURSE: After onset of an antiviral therapy
      (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l
      aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV
      RNA PCR became negative. Unfortunately, after cessation of antiviral treatment
      the patient had a relapse of HCV with a worsening of the arthralgia and the
      Raynaud symptoms (HCV-triggered Sharp}s disease). CONCLUSION: Even in patients
      with mildly abnormal liver function and liver cirrhosis it is important to
      consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

PMID- 17021990
TI  - [Antibiotics, purpura and ulcers: a leukocytoclastic vasculitis after
      clarithromycin].
AB  - HISTORY AND CLINICAL FINDINGS: A 47- year-old woman presented with palpable
      purpura of both lower limbs after taking six tablets of clarithromycin for
      pneumonia. INVESTIGATIONS: Apart from mild microhematuria there were no other
      signs of organ involvement. Histology of a skin biopsy revealed a
      hypersensitivity vasculitis. TREATMENT AND COURSE: A hypersensitivity vasculitis
      due to clarithromycin was the cause of the purpura. The course of this
      hypersensitivity vasculitis was severe and protracted over weeks with formation
      of deep ulcerative skin lesions. CONCLUSION: Clarithromycin may be the cause of a
      hypersensitivity vasculitis: often the course of the disease is mild, but it may
      also lead to severe local complications. The diagnosis of hypersensitivity
      vasculitis can be made in a patient over 16 years of age if there is the
      combination of a triggering substance, purpura and leukocytoclastic vasculitis.
      The most important step is immediate withdrawal of the causative agent. A
      beneficial effect of treatment with steroids on prognosis is not proven.

PMID- 17021992
TI  - [Mechanical ventilation of patients with sepsis].

PMID- 17021993
TI  - [Bronchoscopic diagnosis of peripheral pulmonary foci].
AB  - Flexible fibreoptic bronchoscopy is frequently performed in patients with
      endoscopically not visible lesions, especially for establishing a diagnosis in
      patients with peripheral lung cancer. The usual method for obtaining material for
      histological analysis is transbronchial forceps biopsy. To gain material for
      cytological examination transbronchial needle aspiration, transbronchial catheter
      aspiration or bronchial brushing and bronchial washing can be used. The size of
      the lesion and its location influence the diagnostic accuracy of bronchoscopy.
      The reliability of cytological procedures has found general acceptance: the
      endoscopic investigation can be guided by the results of on-site cytology. The
      combination of transbronchial forceps biopsy and cytological methods increases
      the diagnostic yield. In a direct comparison, cytological examination of material
      from transbronchial needle aspiration and transbronchial catheter aspiration has
      been found to have a significantly higher diagnostic sensitivity than
      transbronchial forceps biopsy in peripheral bronchial carcinoma. While
      transbronchial needle aspiration makes it possible to obtain tissue from
      extrabronchial region, catheter aspiration provides material of a larger area of
      the bronchial mucosa. There is thus no need for an exact positioning of the
      catheter tip inside the lesion under fluoroscopic guidance.

PMID- 17021994
TI  - [Feasibility and humanity in modern medicine. The ethics of progress].

PMID- 17021995
TI  - Effect of five triterpenoid compounds from the buds of Aralia elata on stimulus
      induced superoxide generation, tyrosyl phosphorylation and translocation of
      cytosolic compounds to the cell membrane in human neutrophils.
AB  - The buds of Aralia elata (Miq.) Seem (Japanese angelica tree) have long been used
      as a tonic, antiarthritic and antidiabetic agent in China and Japan. We have
      isolated five triterpenoids, congmuyanosides A, C, D, echinocystic acid and 3-O
      [beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-hederagenin from the buds of
      Aralia elata , and investigated their effects on stimulus-induced superoxide
      generation in human neutrophils. Congmuyanoside A, echinocystic acid and 3-O
      [beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-hederagenin suppressed the
      superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP)
      in a concentration-dependent manner. Congmuyanosides C, D and echinocystic acid
      significantly suppressed the superoxide generation induced by phorbol 12
      myristate 13-acetate (PMA) and arachidonic acid (AA). The compounds also
      suppressed fMLP- and AA-induced tyrosyl or PMA-induced serine/threonine
      phosphorylation and translocation of cytosolic compounds, p47 (phox), p67 (phox)
      and Rac to the cell membrane.

PMID- 17021997
TI  - The inhibition of bone resorption in rats treated with (-)-menthol is due to its
      metabolites.
AB  - (-)-Menthol, a monoterpene from Mentha species (Lamiaceae), has been shown to
      inhibit bone resorption in vivo by an unknown mechanism. In the present study,
      plasma and urine profiling in rats determined by GC/MS demonstrate that (-)
      menthol is extensively metabolized, mainly by hydroxylation and carboxylation,
      and excreted in the urine, in part as glucuronides. In plasma, very low
      concentrations of (-)-menthol metabolites were detected after a single dose of (
      )-menthol, whereas after repeated treatment, several times higher concentrations
      and long residence times were measured. In contrast, the elimination of unchanged
      (-)-menthol was increased by repeated treatment. (-)-Menthol, at concentrations
      found in plasma, did not inhibit bone resorption in cultured mouse calvaria
      (skull). However, the neutral metabolites of (-)-menthol, extracted from urine of
      rats fed with (-)-menthol, inhibited bone resorption in vitro, the concentrations
      being at plasma level or higher. These results suggest that not (-)-menthol
      itself, but one or several of its neutral metabolites inhibit the bone resorbing
      cells in vivo.

PMID- 17021999
TI  - Year-and-a-half old, dried Echinacea roots retain cytokine-modulating
      capabilities in an in vitro human older adult model of influenza vaccination.
AB  - Alcohol tinctures prepared from aged Echinacea roots are typically taken for
      preventing or treating upper respiratory infections, as they are purported to
      stimulate immunity in this context. The effects of long-term (> 1 year) dry
      storage on the capabilities of Echinacea spp. roots from mature individuals to
      modulate cytokine production are unknown. Using an older human adult model of
      influenza vaccination, we collected peripheral blood mononuclear cells from
      subjects 6 months post-vaccination and stimulated them in vitro with the two Type
      A influenza viruses contained in the trivalent 2004-2005 vaccine with a 50 %
      alcohol tincture prepared from the roots of one of seven Echinacea species: E.
      angustifolia, E. pallida, E. paradoxa, E. purpurea, E. sanguinea, E. simulata,
      and E. tennesseensis. Before being processed into extracts, all roots had been
      stored under dry conditions for sixteen months. Cells were cultured for 48 hours;
      following incubation, supernatants were collected and assayed for interleukin-2,
      interleukin-10, and interferon-gamma production, cytokines important in the
      immune response to viral infection. Four species ( E. angustifolia, E. purpurea,
      E. simulata, E. tennesseensis) augmented IL-10 production, diminished IL-2
      production, and had no effect on IFN-gamma production. Echinacea pallida
      suppressed production of all cytokines; E. paradoxa and E. sanguinea behaved
      similarly, although to a lesser extent. The results from these in vitro
      bioactivity assays indicate that dried Echinacea roots stored for sixteen months
      maintain cytokine-modulating capacities. Our data support and extend previous
      research and indicate that tinctures from different Echinacea species have
      different patterns of immune modulation; further, they indicate that certain
      species may be efficacious in the immune response to viral infection.

PMID- 17022001
TI  - The inhibitory effect of triterpenoid glycosides originating from Sanguisorba
      officinalis on tissue factor activity and the production of TNF-alpha.
AB  - We examined the inhibitory effects of novel triterpene glycoside compounds [ziyu
      glycoside II (ZY-II) and its methyl ester (ZYM-201)], which originated from the
      roots of sanguisorba officinalis L. (Rosaceae), on tissue factor (TF) activity
      and tumor necrosis factor (TNF)-alpha production. In in vitro TF activity tests,
      ZY-II but not ZYM-201 strongly blocked lung TF activity with an IC50 value of
      0.46 microM. By contrast, only ZYM-201 dose-dependently inhibited in vivo TF
      activity with an ED50 value of 1.7 mg/kg, when orally administered. Furthermore,
      ZYM-201 diminished both in vitro and in vivo TNF-alpha production with IC50 or
      ED50 values of 69.4 microM and 87.4 mg/kg, respectively. Therefore, these results
      suggest either that ZYM-201 may be developed as a potent inhibitor of both TF-
      and TNF-alpha-mediated diseases such as atherosclerosis and septic shock, or it
      may be a lead compound to be derivatized for further improvement of its curative
      efficacy.

PMID- 17022003
TI  - Characterization of 3alpha-acetyl-11-keto-alpha-boswellic acid, a pentacyclic
      triterpenoid inducing apoptosis in vitro and in vivo.
AB  - 3Alpha-acetyl-11-keto-alpha-boswellic acid (3alpha-acetoxy-11-oxo-olean-12-en-24
      oic acid, 1) was synthesized by a radical-type reaction using bromine and 3alpha
      acetyl-alpha-boswellic acid isolated from the oleo-gum-resin of Boswellia
      carterii. 1D and 2D NMR (COSY, HMBC, ROESY) at 500 MHz were used for shift
      assignments and structure verification. The compound investigated is present in a
      herbal preparation extracted from Boswellia serrata oleo-gum-resin, it inhibits
      the growth of chemotherapy-resistant human PC-3 prostate cancer cells in vitro
      and induces apoptosis as shown by activation of caspase 3 and the induction of
      DNA fragmentation. In addition, compound 1 is active IN VIVO as shown by
      inhibition of proliferation and induction of apoptosis in PC-3 prostate cancer
      cells xenotransplanted onto the chick chorioallantoic membrane.

PMID- 17022004
TI  - Ginkgo biloba leaf extract reverses amyloid beta-peptide-induced isoprostane
      production in rat brain in vitro.
AB  - Isoprostanes are prostaglandin (PG) isomers generated from oxygen radical
      peroxidation of arachidonic acid, which are reliable markers of membrane
      oxidative damage. Aging is characterized by an imbalance between the generation
      of reactive oxygen species and antioxidant detoxification pathways. Ginkgo biloba
      leaf extract is reputed as a neuroprotective antioxidant agent. We have tested
      the effects of a Ginkgo biloba extract {containing 24.1 % flavonoids and 181 %
      terpene lactones [bilobalide (0.542 %), ginkgolide A (0.570 %), ginkgolide B
      (0.293 %), ginkgolide C (0.263 %), and ginkgolide J (0.138 %)]} on the production
      of 8-iso-PGF2alpha from rat brain synaptosomes obtained from young (3 months old)
      or aged (12 and 24 months old) rats, both in the basal state and after oxidative
      stress induced by either hydrogen peroxide or amyloid beta-peptide. Our findings
      show that Ginkgo biloba extract pretreatment is able to completely reverse both
      basal and hydrogen peroxide-stimulated isoprostane production (IC50 of 81.92
      microM and 31.89 microM, respectively). Amyloid beta-peptide-induced isoprostane
      production was also inhibited, both in young and aged rats, to a level even lower
      than that in unstimulated synaptosomes. This suggests that the oxygen radical
      scavenging properties of the Ginkgo biloba extract are fully effective in young,
      as well as in old rats, showing a greater inhibition of isoprostane production in
      the latter.

PMID- 17022005
TI  - Bioactive terpenes from the roots of Chloranthus henryi.
AB  - 12,15-Epoxy-5alpha H,9beta H-labda-8(17),13-dien-19-oic acid (1) and 14-methoxy
      15,16-dinor-5alpha H,9alpha H-labda-13(E),8(17)-dien-12-one (2), two new labdane
      type diterpenes, and 1alpha-hydroxy-8,12-epoxyeudesma-4,7,11-triene-6,9-dione
      (3), one new eudesmane-type sesquiterpene, were isolated from Chloranthus henryi
      Hemsl, along with two known compounds, 8beta H-eudesma-4(14),7(11)-dien-12,8
      olide (4) and 8beta-hydroxyeudesma-4(14),7(11)-dien-12,8-olide (5). Their
      structures were established by a combination of 1D- and 2D-NMR spectroscopic
      techniques. The new compounds 2, 3 and the known compound 4 exhibited antitumor
      activities against Hela and K562 human tumor cell lines.

PMID- 17022006
TI  - Analysis of the essential oil of Origanum dubium growing wild in Cyprus.
      Investigation of its antioxidant capacity and antimicrobial activity.
AB  - The volatile composition of Origanum dubium in two different maturation stages
      has been studied. The essential oils were obtained by hydrodistillation in a
      modified Clevenger-type apparatus, and their analyses were performed by GC and GC
      MS. Identification of the components was made by comparison of mass spectra and
      retention indices with literature records and by co-chromatography with authentic
      compounds. Carvacrol was shown to be the main constituent. The essential oils
      were evaluated for antimicrobial activity and proved to be active against all
      tested microorganisms. Furthermore, their potential antioxidant activity was
      investigated and found to be significant in scavenging O2-. The samples were
      further evaluated for inhibition of soybean lipoxygenase LOX and showed high
      inhibitory activity.

PMID- 17022008
TI  - Anti-inflammatory and cytotoxic diterpenes from formosan Polyalthia longifolia
      var. pendula.
AB  - A new clerodane diterpenoid 16-hydroxycleroda-13-ene-15,16-olide-3-one (1) was
      isolated from the bark of Polyalthia longifolia var. pendula, along with 23 known
      compounds and phytosteroids. Among these compounds, 5 - 7, 10, and 24 were
      obtained for the first time from the family Annonaceae . The structures of the
      isolated compounds were determined by mass and spectroscopic analysis. The
      clerodane diterpenoids, 2 - 4, showed significant cytotoxicity towards Hep G2 and
      Hep 3B hepatoma cell lines. Furthermore, compound 5 exhibited potent anti
      inflammatory activity towards formyl-L-methionyl-L-leucyl-L
      phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide generation by
      neutrophils with IC50 = 0.60 +/- 0.09 microg/mL.

PMID- 17022009
TI  - Third-party prospective evaluation of patient outcomes after dynamic
      graciloplasty.
AB  - BACKGROUND: Dynamic graciloplasty (DGP) is a complex procedure designed to
      improve bowel function in patients with end-stage faecal incontinence. Outcomes
      of DGP were examined in comparison with stoma formation or continued medical
      management. METHODS: This third-party evaluation comprised a prospective case
      comparison study of patient-based and clinical outcomes at a London hospital.
      Forty-nine patients who underwent DGP during 5 years from 1997 were compared with
      87 patients with similar bowel disorders who did not undergo DGP. Outcome
      measures were quality of life (QoL), symptoms, anxiety and depression. RESULTS:
      At 2 years after surgery, bowel-related QoL and continence had improved by more
      than 20 per cent compared with the preoperative status for two-thirds of patients
      who had DGP (P < 0.001). Two-thirds were continent all or most of the time,
      although one-third experienced disordered bowel evacuation. Large deteriorations
      on the Nottingham Health Profile pain score occurred in 11 of 34 patients who had
      DGP, compared with seven of 57 patients in comparison groups (P = 0.027).
      Patients in comparison groups experienced no significant changes in measured
      outcomes over the 2 years of follow-up. CONCLUSION: Although DGP is associated
      with a high level of morbidity, it deserves consideration as an alternative to
      life with severe and refractory faecal incontinence or stoma formation in people
      in whom conventional treatments have failed.

PMID- 17022011
TI  - Management of severe ischaemia of the leg.

PMID- 17022010
TI  - Expression of cyclo-oxygenase 1 and 2, prostaglandin E synthase and transforming
      growth factor beta1, and their relationship with vascular endothelial growth
      factors A and C, in primary adenocarcinoma of the small intestine.
AB  - BACKGROUND: Primary adenocarcinomas of the small intestine are rare. The
      prostaglandin biosynthetic pathway plays a major role in carcinogenesis and is
      linked with angiogenesis in various tumours. Promotion of tumour growth by
      transforming growth factor (TGF) beta may be mediated through the prostaglandin
      pathway. METHODS: Expression of cyclo-oxygenase (COX) 1 and 2, prostaglandin E
      synthase (PGES), TGF-beta1 and vascular endothelial growth factor (VEGF) A and C
      genes was analysed in 54 primary adenocarcinomas of the small intestine and
      corresponding normal intestinal mucosa. All patients had undergone surgical
      resection without previous antineoplastic therapy. Target gene expression was
      analysed at the mRNA level by reverse transcriptase-polymerase chain reaction and
      correlated with clinicopathological parameters as well as survival. COX-2 protein
      expression was examined by immunohistochemistry. RESULTS: Expression of COX-2
      protein was detected immunohistochemically in 98 per cent of the carcinomas. COX
      1, COX-2, VEGF-A, VEGF-C, PGES and TGF-beta1 mRNA expression varied markedly in
      different tumours, but all were overexpressed compared with levels in normal
      intestinal mucosa. There were significant associations between levels of COX-1,
      COX-2, TGF-beta1 and PGES mRNAs and those of VEGF-A and VEGF-C. CONCLUSION:
      Correlations between levels of mRNA for COX-1, COX-2, TGF-beta1 and PGES and
      those for proangiogenic factors VEGF-A and VEGF-C suggest a role for these
      factors in the propagation of primary adenocarcinomas of the small intestine.

PMID- 17022012
TI  - Impact of highly active antiretroviral therapy on outcome of cholecystectomy in
      patients with human immunodeficiency virus infection.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) reduces virus
      proliferation and significantly decreases the rate of septic and opportunistic
      complications in patients infected with human immunodeficiency virus (HIV).
      Although surgery is performed routinely on patients receiving HAART, the effect
      of this treatment on surgical outcome has not been examined in detail. METHODS:
      This retrospective study reviewed 54 consecutive patients with HIV infection who
      underwent surgical cholecystectomy: 31 patients were on HAART, 13 on nucleoside
      analogue reverse transcriptase inhibitors (NRTIs) and ten were receiving no
      specific therapy. Characteristics of HIV-1 infection, laboratory investigations,
      characteristics of the gallbladder disease, type of operation, postoperative
      course, morbidity and mortality were recorded. Univariable analysis and
      unconditional logistic regression were performed to determine factors related to
      postoperative complications and death. RESULTS: The three groups were similar in
      terms of HIV-1 infection characteristics. In univariable analysis HAART and
      laparoscopic cholecystectomy were associated with a significantly lower
      complication rate, whereas only HAART was shown to be protective by logistic
      regression analysis. A low HIV RNA load and a high CD4(+) cell count were
      significant predictors of uncomplicated surgical outcomes. CONCLUSION: HAART
      significantly reduces the risk of complications after cholecystectomy in patients
      with HIV infection or acquired immune deficiency syndrome.

PMID- 17022013
TI  - Clinical significance of splanchnic artery stenosis.
AB  - BACKGROUND: The clinical relevance of splanchnic artery stenosis is often
      unclear. Gastric exercise tonometry enables the identification of patients with
      actual gastrointestinal ischaemia. A large group of patients with splanchnic
      artery stenosis was studied using standard investigations, including tonometry.
      METHODS: Patients referred with possible intestinal ischaemia were analysed
      prospectively, using duplex imaging, conventional abdominal angiography and
      tonometry. All results were discussed within a multidisciplinary team. RESULTS:
      Splanchnic stenoses were found in 157 (49.7 percent) of 316 patients; 95 patients
      (60.5 percent) had one-vessel, 54 (34.4 percent) two-vessel and eight (5.1
      percent) had three-vessel disease. Chronic splanchnic syndrome was diagnosed in
      107 patients (68.2 percent), 54 (57 percent) with single-vessel, 45 (83 percent)
      with two-vessel and all eight with three-vessel stenoses. Treatment was
      undertaken in 95 patients, 62 by surgery and 33 by endovascular techniques. After
      a median follow-up of 43 months, 84 percent of patients were symptom free.
      CONCLUSION: Gastric exercise tonometry proved crucial in the evaluation of
      possible intestinal ischaemia. Comparing patients with single- and multiple
      vessel stenoses, there were significant differences in clinical presentation and
      mortality rates.

PMID- 17022014
TI  - Outcome and cost analysis of sacral nerve stimulation for faecal incontinence.
AB  - BACKGROUND: Sacral nerve stimulation (SNS) may be successful in treating
      incapacitating faecal incontinence. The technique is expensive, and no cost
      analysis is currently available. The aim of this study was to assess clinical
      outcome and analyse cost-effectiveness. METHODS: Thirty-six consecutive patients
      underwent a two-stage SNS procedure. Outcome parameters and real costs were
      assessed prospectively. RESULTS: SNS was tested successfully in 33 of 36
      patients, and 31 patients were stimulated permanently. In the first stage, eight
      of 36 patients reported minor complications (pain, infection or electrode
      dislocation), resulting in a cost of euro 4053 (range euro 2838-7273) per
      patient. For the second stage (permanent stimulation), eight of 33 patients had
      an infection, pain or loss of effectiveness, resulting in a cost of euro 11,292
      (range euro 7406-20,274) per patient. Estimated costs for further follow-up were
      euro 997 per year. The 5-year cumulative cost for SNS was euro 22,150 per
      patient, compared with euro 33,996 for colostomy, euro 31,590 for dynamic
      graciloplasty and euro 3234 for conservative treatment. CONCLUSION: SNS is a
      highly cost-effective treatment for faecal incontinence. Options for further
      reduction of SNS costs include strict patient selection, treatment in an
      outpatient setting and using cheaper devices.

PMID- 17022015
TI  - Online acid barrage stacking anti-salt injection for capillary electrophoresis of
      9-fluorenylmethylchloroformate-derivatized amino acids in high ionic strength
      solutions by UV detection.
AB  - An acid barrage stacking (ABS) method has been shown to be feasible for online
      anti-salt injection in CE of 9-fluorenylmethyl chloroformate (FMOC)-labeled amino
      acids (AAs) detected by common UV absorption. The operation was performed on
      normal polar CE by sucking in an extra plug of acid following a sample zone,
      serving as a selective acid barrage to block the backward migration of weak
      anionic analytes due to a sudden mobility reduction via acid-base reaction which
      does not affect strong co-ions such as Cl(-) to penetrate the barrage freely. By
      CE-UV of FMOC-AAs in various NaCl solutions, the effectiveness of ABS was firmly
      validated, able to stand up to 500 mM NaCl and to stack analytes by 10(3)-fold
      calculated from the UV detection limits, that is 0.01 microM for ABS and 10
      microM for non-stacking injection. The method was also validated by determining
      trace Glu and Asp in real samples of rat brain microdialysate, rat serum and
      human saliva. The intraday RSDs were 0.33-4.9% for migration time and 1.8-9.6%
      for peak area. The recoveries measured by spiking technique were 82-115% for Glu
      and 86-116% for Asp. Working equations were obtained by plotting peak height vs.
      concentration at 0.1-50 microM, with correlation coefficients of >0.999. The
      contents of Glu and Asp were thus found at 0.26-0.83 microM and 0.24-0.64 microM
      respectively, in rat brain microdialyste; 37-40 microM and 8.4-10 microM,
      respectively, in rat serum; and 3.5-5.8 microM and 1.0-4.1 microM, respectively
      in human saliva. They were consistent with the data from other methods.

PMID- 17022016
TI  - Analysis of triazines by capillary electrochromatography/electrospray ionization
      mass spectrometry using a low-flow sheath liquid interface.
AB  - CEC-MS has been used for the analysis of eight-triazine herbicides. It showed
      significantly better S/N ratio than reversed EOF CE-MS and MEKC-MS, due to the
      lack of a surfactant in the separation buffer. By optimizing the pH, the organic
      content of the running buffer, and the separation potential, optimal separation
      was achieved within 18 min using a running buffer of pH 7.0, containing 70% v/v
      ACN, and an applied voltage of 17 kV. Gradient CEC showed superior separation
      when compared with isocratic elution. The combination of a tapered CEC column and
      a low-flow interface confers several advantages including better sensitivity, low
      dead volume, and independent control of the conditions used for CEC separation
      and ESI analysis.

PMID- 17022017
TI  - Microchip-based CEC of nitroaromatic and nitramine explosives using silica-based
      sol-gel stationary phases from methyl- and ethyl-trimethoxysilane precursors.
AB  - Microchip-based CEC of nitroaromatic and nitramine explosives with UV absorbance
      detection is described. The stationary phase was deposited in the microchip using
      the sol-gel process. Unique to this work, is the exclusive use of alkylated
      trimethoxysilane precursors in the gel solution. Using alkylated precursors
      allows for the synthesis of a hydrophobic stationary phase in a single step.
      Three sol-gel formulations of increasing hydrophobicity and suitable for the
      separation of explosives are established from methyl- and ethyl-trimethoxysilane
      precursors. Increasing the alkyl-chain length improved the resolution
      significantly, allowing for the separation of up to seven analytes. Direct
      injection onto the head of the stationary phase for long injection times, results
      in sub-mg/L detection limits with little effect on separation efficiency.

PMID- 17022018
TI  - Delta-cyclodextrin as novel chiral probe for enantiomeric separation by
      electromigration methods.
AB  - Native delta-CD has been employed as chiral selector in CE and MEKC. To
      investigate the potential of the enantiodiscriminating properties of delta-CD,
      negatively charged 5-dimethylamino-1-naphthalene-sulfonyl (dansyl)-, 2,4
      dinitrophenyl (DNP)- and FMOC-derivatives of several amino acids, 1,1'-binaphthyl
      2,2'-diylhydrogenphosphate, flavanones and three positively charged drugs have
      been selected as testing samples. Enantioresolution factors up to 4.82 have been
      observed. The results were compared with those achieved by the conventional
      running buffer additives alpha-, beta- and gamma-CDs. For several examples a
      steady increase of enantioresolution with increasing degree of oligomerization
      has been detected.

PMID- 17022019
TI  - CZE of human alpha-1-acid glycoprotein for qualitative and quantitative
      comparison of samples from different pathological conditions.
AB  - Alpha-1-acid glycoprotein (AGP) presents different forms, which may arise from
      differences in the amino acid sequence and/or in the glycosidic part of the
      protein. Changes in forms of AGP have been described in literature as a possible
      tumor marker. While most previous works have approached the study of
      glycopeptides and/or glycans obtained after fragmentation of the protein, in this
      work, a CZE method is developed to separate up to eleven peaks of intact forms of
      AGP. A computer program developed in our laboratory is used to select the
      migration parameters that make possible an accurate assignment of AGP peaks.
      Electropherograms of AGP samples purified from sera of cancer patients and
      healthy donors are qualitatively and quantitatively compared. Percentages of
      correct assignment of AGP peaks close to 100% are achieved by using either the
      migration time of each peak relative to that of the EOF marker or the effective
      electrophoretic mobility of the peaks. The computer program permits to select,
      among different hypotheses for peak allotment, that one providing the highest
      accuracy of assignment. In this way, some peaks with different charge-to-mass
      ratio and a different distribution of area percentage of AGP forms are observed
      when comparing samples from sick and healthy individuals. Thus, a method that
      permits to compare AGP forms existing in sera of individuals with different
      pathophysiological situations has been developed. A potential for using AGP forms
      analyzed by CZE as a disease marker and for using this technique for screening
      purposes is envisaged.

PMID- 17022020
TI  - Anti-cancer properties of anthraquinones from rhubarb.
AB  - Rhubarb has been used as a traditional Chinese medicine since ancient times and
      today it is still present in various herbal preparations. In this review the
      toxicological and anti-neoplastic potentials of the main anthraquinones from
      Rhubarb, Rheum palmatum, will be highlighted. It is interesting to note that
      although the chemical structures of various anthraquinones in this plant are
      similar, their bioactivities are rather different. The most abundant
      anthraquinone of rhubarb, emodin, was capable of inhibiting cellular
      proliferation, induction of apoptosis, and prevention of metastasis. These
      capabilities are reported to act through tyrosine kinases, phosphoinositol 3
      kinase (PI3K), protein kinase C (PKC), NF-kappa B (NF-kappaB), and mitogen
      activated protein kinase (MAPK) signaling cascades. Aloe-emodin is another major
      component in rhubarb found to have anti-tumor properties. Its anti-proliferative
      property has been demonstrated to be through the p53 and its downstream p21
      pathway. Our recent proteomic study also suggests that the molecular targets of
      these two anthraquinones are different. However, both components were found to be
      able to potentiate the anti-proliferation of various chemotherapeutic agents.
      Rhein is the other major rhubarb anthraquinone, although less well studied. This
      compound could effectively inhibit the uptake of glucose in tumor cells, caused
      changes in membrane-associated functions and led to cell death. Interestingly,
      all three major rhubarb anthraquinones were reported to have in vitro phototoxic.
      This re-evaluation of an old remedy suggests that several bioactive
      anthraquinones of rhubarb possess promising anti-cancer properties and could have
      a broad therapeutic potential.

PMID- 17022021
TI  - Coupling of acetonitrile deproteinization and salting-out extraction with
      acetonitrile stacking for biological sample clean-up and the enrichment of
      hydrophobic compounds (porphyrins) in capillary electrophoresis.
AB  - A new sample pretreatment approach in CE was developed for concurrent biological
      sample clean-up and the concentration of hydrophobic compounds based on the
      combination of ACN deproteinization with salting-out extraction. Further
      enhancement in concentration detection sensitivity was achieved by coupling
      (offline) salting-out extraction with an online CE sample enrichment technique
      known as "ACN stacking". By optimizing the pH of salting-out extraction, a number
      of model compounds (hydrophobic porphyrins with clinical significances), i.e.
      zinc-protoporphyrin, protoporphyrin, and coproporphyrin (CP) III and I, can be
      efficiently extracted from the aqueous sample into a smaller volume organic
      solvent (ACN) phase and an enrichment factor of ca. 100 can be obtained. The
      pressure injection of the enriched ACN phase (containing ca.1% NaCl) into the CE
      capillary at 10% capillary volume resulted in additional concentration of the
      various hydrophobic porphyrins, allowing for a combined enrichment factor of
      ca.1000 to be obtained. Calibration curves obtained for the determination of a
      pair of positional isomers with significant diagnostic value, urinary CPIII and
      CPI, were found to be linear between 10-300 ng/mL (with R2 = 0.999), and LODs
      (absorbance detection at 400 nm) were ca. 0.8 ng/mL (1.1 nmol/L of CPIII or CPI).
      Based on a single salting-out extraction, intraday precisions (nine consecutive
      injections) for both CPIII and CPI (at spiked concentrations of 10-300 ng/mL into
      urine) in terms of migration time and peak area were found to be within the range
      of 0.2-0.5 and 0.8-2.9%, respectively.

PMID- 17022022
TI  - An unusual formation of the deep palmar arch.

PMID- 17022024
TI  - Bilateral accessory renal arteries with retroaortic left renal vein: report of an
      elderly cadaver case.

PMID- 17022023
TI  - Potential association between infertility and spinal neural tube defects in
      offspring.
AB  - BACKGROUND: We examined the possible association between infertility and spinal
      neural tube defects (NTDs). METHODS: This is a nested case-control study within
      the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among
      a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997,
      we electronically identified cases of spinal NTDs and confirmed the diagnosis by
      chart review. Controls (n = 1,608) were randomly selected from the birth
      population. History of infertility was defined as: (1) physician diagnosis of
      infertility; (2) prescription for an infertility medication noted in the KPMCP
      pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern
      California. RESULTS: Eighteen infants diagnosed with spinal NTDs (prevalence
      1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida
      occulta. Case mothers were more likely to have a history of infertility (4/18 vs.
      96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene
      citrate within the window spanning 60 days before to 15 days after conception
      (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8). CONCLUSION: This exploratory study
      suggests that infertility may be associated with an increased risk of spinal NTDs
      among liveborn, term infants.

PMID- 17022025
TI  - Reduction of all-trans-retinoic acid-induced teratogenesis in the rat by glycine
      administration.
AB  - BACKGROUND: Prenatal rat embryo exposure to retinoids induces severe
      malformations in various organs; the most active and teratogenic metabolite is
      all-trans-retinoic acid (atRA). The mechanisms of this embryopathy are only
      partly known. In the present study, the influence of glycine on the
      teratogenicity of atRA was investigated. METHODS: Embryos from 5 groups of white
      rats were studied: Group 1 remained untreated; Group 2 received glycine 2% in
      drinking water ad libitum from the first gestational day (GD 1); Group 3 was
      administered vehicle (corn oil); Group 4 was treated with atRA (50 mg/kg of body
      weight) injected (IP); and Group 5 was treated with atRA (50 mg/kg of body weight
      IP) plus glycine 2% in drinking water ad libitum from GD 1. atRA was
      administrated daily from GD 8-10. Dams were killed on the 21st day of pregnancy,
      and their fetuses were examined to detect external, visceral, and skeletal
      malformations. RESULTS: The results show that the atRA-administered dose is not
      toxic for the dams, and that although fetal death was not observed, it produced
      abnormalities in the fetuses. Glycine reduced atRA-induced teratogenic effects
      (external and skeletal defects). CONCLUSIONS: The results indicate that glycine
      effectively reduces the teratogenic effects of atRA. Thus, glycine might be
      useful for the prevention of vitamin A teratogenicity.

PMID- 17022026
TI  - Anatomic variations of the musculotendinous junction of the soleus muscle and its
      clinical implications.
AB  - The soleus muscle, like the gastrocnemius, is a powerful plantarflexor muscle in
      the lower limb. The soleus muscle joins the aponeurosis of the gastrocnemius
      muscle to form the calcaneal (Achilles) tendon. While the basic anatomy of the
      soleus muscle has been previously described, no study has addressed the
      anatomical variations of its distal attachment. We found considerable anatomic
      variation in the distance between this musculotendinous junction and the most
      proximal point of the proximal edge. This distal measuring point was defined as
      the most proximal point of the proximal edge of the posterior surface of the
      calcaneal tuberosity. Eighty human cadaver specimens were preserved according to
      Thiel's method; we examined one limb from each cadaver, studying 80 lower
      extremities in total. Following careful dissection of the lower limb, we measured
      the distance between the distal point of attachment of the soleus muscle fibers
      (the musculotendinous junction) and the designated measuring point. Our findings
      were divided into three groups: Group 1 (10 cases, 12.5%), where the distance
      between the musculotendinous junction and the designated point on the calcaneal
      tuberosity was between 0 and 1 inches; Group 2 (56 cases, 70%), where the
      distance was between 1 and 3 inches; and Group 3 (14 cases, 17.5%), where the
      distance was greater than 3 inches. Detailed knowledge of the anatomic variations
      of the soleus muscle at its insertion point onto the calcaneal tendon has
      clinical implications in calcaneal tendon repair following rupture and in the
      planning of reconstructive surgery using soleus muscle flaps.

PMID- 17022027
TI  - Musculocutaneous nerve: histotopographic study and clinical implications.
AB  - Surgical reconstruction of severe brachial plexus injuries includes nerve
      grafting and neurotization techniques of the musculocutaneous nerve (MCN) to
      recover elbow flexion. In treating recurrent anterior shoulder instability,
      knowledge of the topography of the MCN is important for the margin of safety
      available during dissection. The present study evaluates the origin and course of
      the MCN and its branches, and their relationships to bone landmarks. Twelve
      unembalmed cadavers (50-82 years old) were dissected. A histological study of the
      MCN and the coracobrachialis muscle (CB) was also carried out. The mean distance
      (+/-SD) of the MCN from the coracoid process to the origin, points of entry to,
      and exit from the CB were 2.9 +/- 0.5 cm, 7.7 +/- 2.5 cm, and 11.6 +/- 0.8 cm,
      respectively. The first two findings were also validated during surgical
      approaches to the shoulder in 59 subjects. The mean distance of the MCN from the
      acromion to the origin, points of entry to, and exit from the CB were 6.4 +/- 0.3
      cm, 7.7 +/- 0.8 cm, and 10.4 +/- 1.9 cm, respectively. The mean length of the MCN
      from its origin to the points of entry to and exit from the CB were 6.7 +/- 1.6
      cm and 11.0 +/- 1.0 cm, respectively. The mean length of the MCN inside the
      muscle was 4.4 +/- 1.9 cm. The distance from the coracoid process to the point of
      entry to the CB and the length of the MCN inside the muscle were inversely
      related (P < 0.05). The distance from the coracoid process to the point of exit
      of the MCN was positively correlated with the length of the nerve within the CB
      (P < 0.05). Histology showed that, during the intramuscular course of the MCN,
      the epineurium is composed of 4-5 concentrically arranged lamina of connective
      tissue which shows different dispositions along the circumference of the nerve
      trunk. On the ventral and dorsal aspects of the nerve the lamina are closely
      packed, but on the medial and lateral sides they are separated by thin layers of
      adipose tissue. This uneven disposition of the adipose tissue gives the
      epineurium an oval profile in transverse section (mean circular factor 0.8). The
      arrangement of the fibroadipose tissue sheaths may be compared to a "telescope"
      and may allow compliance between variations of length of CB and the constant
      course of the MCN. Clinically, a decrease in this "sliding system" may expose the
      nerve to mechanical effects of muscle contraction, with the possibility of a
      compression syndrome.

PMID- 17022028
TI  - Chemical modification of therapeutic drugs or drug vector systems to achieve
      targeted therapy: looking for the grail.
AB  - Most therapeutic drugs distribute to the whole body, which results in general
      toxicity and poor acceptance of the treatments by patients. The targeted delivery
      of chemotherapeutics to defined cells, either stromal or cancer cells in cancer
      lesions, or defined inflammatory cells in immunological disorders, is one of the
      main challenges and a very active field of research in the development of
      treatment strategies to minimize side-effects of drugs. Disease-associated cells
      express molecules, including proteases, receptors, or adhesion molecules, that
      are different or differently expressed than their normal counterparts. Therefore
      one goal in the field of targeted therapies is to develop chemically derivatized
      drugs or drug vectors able to target defined cells via specific recognition
      mechanisms and also able to overcome biological barriers. This article will
      review the approaches which have been explored to achieve these goals and will
      discuss in more detail three examples (i) the use of nanostructures to take
      advantage of increased vascular permeability in some human diseases, (ii) the
      targeting of therapeutic drugs to an organ, the brain, protected against foreign
      molecules by the blood-brain barrier, and (iii) the use of the folate receptor to
      target either tumor cells or activated macrophages.

PMID- 17022029
TI  - Surgical anatomy of the external branch of the superior laryngeal nerve.
AB  - Palsy of the external branch of the superior laryngeal nerve (EBSLN) during
      thyroid surgery is an important complication reported with varying frequency.
      This study was carried out to investigate the relationship between the EBSLN, the
      upper part of the thyroid gland and the inferior constrictor muscle of the
      pharynx (IC), and also to define consistent landmarks for identifying and
      preserving the EBSLN. Forty neck halves of 20 cadavers were dissected.
      Measurements were obtained between the crossing point of the EBSLN with the
      superior thyroid artery (STA) and the upper pole of the thyroid gland, the point
      where EBSLN penetrates the IC and the inferior thyroid tubercle, and the middle
      point of the oblique line of the thyroid cartilage, and the EBSLN. In 22.5%, the
      EBSLN crossed the STA more than 1 cm above the upper pole of the thyroid gland
      (Type I of Cernea et al. [1992a] Head Neck 14:380-383). In 60%, the EBSLN crossed
      the STA less than 1 cm above the upper pole of the thyroid gland (Type IIa of
      Cernea et al. [1992a] Head Neck 14:380-383). In 17.5%, the EBSLN crossed the STA
      under the upper pole of the thyroid gland (Type IIb of Cernea et al. [1992a],
      Head Neck 14:380-383). In 22.5%, the full course of the nerve was superficial to
      the IC (Type 1 of Friedman et al. [2002] Arch Otolaryngol Head Neck Surg 128:296
      303). In 67.5%, the nerve penetrated the IC (Type 2 of Friedman et al. [2002]
      Arch Otolaryngol Head Neck Surg 128:296-303). In 10%, the nerve could not be
      identified at the lateral side of the IC (Type 3 of Friedman et al. [2002] Arch
      Otolaryngol Head Neck Surg 128:296-303). In conclusion, it is possible to
      identify the nerve superficial to the IC in 90% of specimens on average.
      Knowledge of the relationship between the EBSLN, IC, inferior thyroid tubercle,
      oblique line of the thyroid cartilage and the sternothyroid muscle will be useful
      for the surgeon in avoiding unexpected complications.

PMID- 17022030
TI  - Racial differences in infant mortality attributable to birth defects in the
      United States, 1989-2002.
AB  - BACKGROUND: The objective is to study racial differences in infant mortality
      attributable to birth defects (IMBD) in the United States. METHODS: We analyzed
      1989-1991 and 1995-2002 linked birth/death files for trends and racial
      differences in IMBD by selected categories of birth defects for infants of non
      Hispanic white, non-Hispanic black, and Hispanic mothers. RESULTS: In 1989-2002,
      the IMBD rates declined. However, the decline in postneonatal mortality
      attributable to birth defects (PMBD) rate was significantly slower than that of
      overall postneonatal mortality. The adjusted rate ratio for non-Hispanic black
      and Hispanic versus non-Hispanic white for neonatal mortality attributable to
      birth defects (NMBD) remained unchanged from 1989-1991 through 2000-2002. For
      PMBD, it increased from 0.97 (95% confidence interval [CI], 0.90-1.13) in 1989
      1991 to 1.12 (95% CI, 1.04-1.21) in 2001-2002 and from 1.08 (95% CI, 1.00-1.16)
      to 1.18 (95% CI, 1.10-1.27) for non-Hispanic black and Hispanic, respectively.
      Infant mortality due to cardiovascular and central nervous system defects were
      the main contributors to the increased racial disparities in PMBD rates.
      CONCLUSIONS: The disparity in PMBD between infants of non-Hispanic black and
      Hispanic mothers and infants of non-Hispanic white mothers increased
      significantly from 1989-1991 to 2000-2002. Further studies are needed to assess
      the extent to which delays in care or lack of access to care for infants with
      birth defects might be contributing to the disparity in IMBD.

PMID- 17022031
TI  - A case of an atypical radial artery.

PMID- 17022032
TI  - Intervention with bacterial adhesion by multivalent carbohydrates.
AB  - Bacterial adhesion is often a prelude to infection. In many cases, this process
      is governed by protein-carbohydrate interactions. Intervention at this early
      stage of infection is a conceptually highly attractive alternative to
      conventional antibiotics that are increasingly prone to resistance. The lack of
      high-affinity inhibitors of adhesion has proven to be a hurdle for further
      exploitation of this concept; however, new developments indicate a positive
      change. Structure-based design at the monovalent level and also evaluation of
      glycodendrimers and glycopolymers have yielded structures of high affinity. In
      addition to the development of inhibitors, topics of this review include
      available structural information of adhesion proteins, carbohydrate specificities
      of the various pathogens and their adhesion proteins. Other new developments
      aimed at affecting bacterial adhesion and the use of the adhesins for bacterial
      detection are also discussed.

PMID- 17022033
TI  - Anatomical considerations on Sudeck's critical point and its relevance to
      colorectal surgery.
AB  - Sudeck's critical point at the rectosigmoid junction is described as the point of
      origin of the last sigmoid arterial branch, originating from the inferior
      mesenteric artery (IMA). There is controversy on the importance of Sudeck's
      point, and the frequency in which the anastomosis is found. Furthermore, the
      diameter of the anastomosis, if present, may also impact on the viability of the
      caudal stump. This study aimed to determine the frequency in which a macroscopic
      anastomosis occurs, between the superior rectal artery and the last sigmoidal
      branch, in a cadaver population; the diameter of this anastomosis and the
      distance from the origin of the IMA to Sudeck's point. Sixty-four cadavers were
      included in the study, excluding those with previous surgery to the rectosigmoid
      junction. Sudeck's point was carefully identified and dissected to establish the
      presence of an anastomosis. Subsequent measurements were performed using a
      digital caliper (accuracy = 0.01 mm). A macroscopic anatomosis was absent in
      three cases (4.7%). The mean diameter of the anastomosis when present was 1.9 mm
      (SD: 0.5 mm), and the distance from the origin of the IMA to Sudeck's point was
      55.5 mm (SD: 14.6 mm). Although an anastomosis is present in the majority of
      cases, the vessel is very small in diameter, and may not be sufficient to meet
      the demands of the caudal stump. The distance from the origin of the IMA to
      Sudeck's point is sufficient enough to allow for ligation of the IMA proximal to
      Sudeck's point.

PMID- 17022034
TI  - A clinicoanatomical study of the novel nerve fibers linked to stress urinary
      incontinence: the first morphological description of a nerve descending properly
      along the anterior vaginal wall.
AB  - When performing anterior colporrhaphy for cystocele, most pelvic surgeons have
      not considered the neuroanatomy that contributes to urethral function. The aim of
      the study was to anatomically identify nerve fibers located in the anterior
      vagina associated with the pathogenesis of incontinence and pelvic organ
      prolapse. Anterior vaginal specimens were obtained from 17 female cadavers and 33
      cases of clinical cystocele by anterior vaginal resection. The specimens were
      step-sectioned and stained with hematoxylin-eosin, S100 antibody, and tyrosine
      hydroxylase antibody. As a result, descending nerves 50-200 microm in thickness
      were identified between the urethra and vagina. They were located more than 10 mm
      medially from a cluster of nerves found almost along the lateral edge of the
      vagina and stained with S100 and tyrosine hydroxylase antibody, originated from
      the cranial part of the pelvic plexus, and appeared to terminate at the urethral
      smooth muscles. The authors classified the density of S100 positive nerve fibers
      in the anterior vaginal wall obtained from clinically operated cases of cystocele
      into three grades (Grade 1, nothing or a few thin nerves less than 20 microm in
      diameter; Grade 2, thick nerves more than 50 microm in diameter and thin nerves;
      Grade 3, more than 3 thick nerves in one field at an objective magnification of
      40x). Mean urethral mobility (Q-tip) values (28.1 degrees +/-+/- 19.6 degrees )
      observed in the Grade 3 cases was significantly lower than those (50.0 degrees +/
      +/- 27.4 degrees and 59.4 degrees +/-+/- 19.9 degrees ) in Grade 2 and Grade 1,
      respectively. In addition, the presence of preoperative or postoperative stress
      urinary incontinence in the cases of Grade 1 was significantly higher than those
      of the cases with S100 positive stained nerves. In conclusion, the novel nerve
      fibers immunohistochemically identified in the anterior vaginal wall are
      different from those of the common nervous system or the pelvic floor and are
      associated with the pathogenesis of urethral hypermobility.

PMID- 17022035
TI  - Aplastic patella tissue in a patient with isolated patella aplasia-hypoplasia.

PMID- 17022036
TI  - Cationic liposomes as non-viral carriers of gene medicines: resolved issues, open
      questions, and future promises.
AB  - The clinical success of gene therapy is critically dependent on the development
      of efficient and safe gene delivery reagents, popularly known as "transfection
      vectors." The transfection vectors commonly used in gene therapy are mainly of
      two types: viral and non-viral. The efficiencies of viral transfection vectors
      are, in general, superior to their non-viral counterparts. However, the myriads
      of potentially adverse immunogenic aftermaths associated with the use of viral
      vectors are increasingly making the non-viral gene delivery reagents as the
      vectors of choice. Among the existing arsenal of non-viral gene delivery
      reagents, the distinct advantages associated with the use of cationic
      transfection lipids include their: (a) robust manufacture; (b) ease in handling
      and preparation techniques; (c) ability to inject large lipid:DNA complexes; and
      (d) low immunogenic response. The present review highlights the major
      achievements in the area of designing efficacious cationic transfection lipids,
      some of the more recent advances in the field of cationic liposomes-mediated gene
      transfer and targeted gene delivery, some unresolved issues and challenges in
      liposomal gene delivery, and future promises of cationic liposomes as gene
      carriers in non-viral gene therapy.

PMID- 17022037
TI  - Role of potassium channels in Abeta(1-40)-activated apoptotic pathway in cultured
      cortical neurons.
AB  - Potassium channel dysfunction has been implicated in Alzheimer's disease (AD). In
      the present study, by using potassium channel blocker tetraethylammonium (TEA),
      we investigated the relationship between the enhancement of potassium currents
      and the alteration of apoptotic cascade in the neuronal apoptotic model induced
      by beta-amyloid peptide 1-40(Abeta(1-40)). Cortical neurons exposed to Abeta(1
      40) 5 muM developed a specific increase in the delayed rectifier potassium
      current (I(K)), but not the transient outward potassium currents (I(A)), before
      the appearance of neuronal apoptosis. Abeta(1-40) induced various apoptotic
      features such as chromatin condensation, a decrease in the amount of Bcl-2
      protein, an increase in the amount of Bax protein, cytochrome c release from
      mitochondria, and caspase-3 activation. Potassium channel blocker 5 mM TEA
      attenuated Abeta(1-40)-induced neuronal death and prevented the alterations of
      all above mentioned apoptotic indicators. The study indicates that I(K)
      enhancement might play an important role in certain form of programmed cell death
      induced by beta-amyloid peptide (Abeta). Increased potassium channel activity
      might trigger the activation of apoptosis cascade in Abeta(1-40)-treated rat
      cortical neurons.

PMID- 17022038
TI  - Degeneration of neuronal cell bodies following axonal injury in Wld(S) mice.
AB  - The phenotype of Wld(S) ("slow Wallerian degeneration") mice demonstrates
      prolonged survival of injured axons. However, whether the Wld(S) mutation delays
      degeneration of the neuronal cell body following axonal injury is unclear. We
      used a retrograde model of axonal transport failure in Wld(S) mice to test
      whether the mutant Wld(S) protein has any beneficial effect on the neuronal cell
      body. Retrograde axonal transport was physically blocked by optic nerve crush and
      confirmed by the absence of Fluoro-Gold labeling in wild-type and in Wld(S) mice.
      After this axonal injury, there was marked protection of axonal degeneration in
      the Wld(S) phenotype, as confirmed by immunohistochemistry and electron
      microscopy. However, the Wld(S) protein, localized in the nucleus of retinal
      ganglion cells, did not prevent or delay degeneration of the retinal ganglion
      cell body, confirmed by TUNEL staining and Fluoro-Gold labeling. These results
      imply that, after axonal injury, Wallerian degeneration of axons and degeneration
      of the neuronal cell body have different mechanisms, which are autonomous and
      independent of each other. Although the Wld(S) phenotype can be used to
      demonstrate stable enucleate axons, the mutation is unlikely to protect neurons
      in neurodegenerative diseases in which there is failure of retrograde transport.

PMID- 17022039
TI  - Pituitary adenylate cyclase-activating polypeptide-induced differentiation of
      embryonic neural stem cells into astrocytes is mediated via the beta isoform of
      protein kinase C.
AB  - We have found previously that pituitary adenylate cyclase-activating polypeptide
      (PACAP) increases the number of astrocytes generated from cultured mouse neural
      stem cells (NSCs) via a mechanism that is independent of the cyclic AMP/protein
      kinase A pathway (Ohno et al., 2005). In the present study, the signaling pathway
      involved in the differentiation process was further investigated. PACAP-induced
      differentiation was inhibited by the phospholipase C inhibitor, U73122, the
      protein kinase C (PKC) inhibitor, chelerythrine, and the intracellular calcium
      chelator, BAPTA-AM, and was mimicked by phorbol 12-myristate 13-acetate (PMA),
      but not by 4alpha-PMA. These results suggest that the PACAP-generated signal was
      mediated via the PACAP receptor, PAC1 stimulated heterotrimeric G-protein,
      resulting in activation of phospholipase C, followed by calcium- and phospholipid
      dependent protein kinase C (cPKC). To elucidate the involvement of the different
      isoforms of cPKC, their gene and protein expression were examined. Embryonic NSCs
      expressed alpha and betaII PKC, but lacked PKCgamma. When NSCs were exposed to 2
      nM PACAP, protein expression levels of the betaII isoform transiently increased
      two-fold before differentiation, returning to basal levels by Day 4, whereas the
      level of PKCalpha increased linearly up to Day 6. Overexpression of PKCbetaII
      with adenovirus vector synergistically enhanced differentiation in the presence
      of 1 nM PACAP, whereas expression of the dominant-negative mutant of PKCbetaII
      proved inhibitory. These results indicate that the beta isoform of PKC plays a
      crucial role in the PACAP-induced differentiation of mouse embryonic NSCs into
      astrocytes.

PMID- 17022040
TI  - Jean Casimir Felix Guyon--urologist and anatomist.

PMID- 17022041
TI  - Combined unusual anatomical variations of the superior mesenteric and right renal
      arteries.

PMID- 17022042
TI  - Anatomic study of the synovial folds of the occipito-atlanto-axial joints.
AB  - This study was performed to observe and measure synovial folds of the occipito
      atlanto-axial joints and to explore their clinical significance. Two hundred
      ninety eight occipito-atlanto-axial joints from 30 embalmed cadavers of children
      and 20 of adults were dissected to find the incidence, quantity, distribution,
      forms, dimension, and histology of synovial folds. Synovial folds were found in
      most joints in both groups except for the posterior median atlantoaxial joints.
      Most of synovial folds were crescent-shaped, distributed on the superior aspects
      of the anterior median atlantoaxial joints, or in the antero-lateral aspects of
      the atlantooccipital joints and the lateral atlantoaxial joints. Compared to the
      adult group, the child group had a higher incidence of synovial folds (72.5%
      joints). The adult incidence was found to be 58.5%. 54.3% of the synovial folds
      in child were medium size or large size, but only 30.1% of the synovial folds in
      adult were medium size and there were no large ones. Microscopically, there were
      three histologic types synovial folds in these cervical joints, and 78.9% of them
      belonged to adipose type or fibro-adipose type in child, but only 45.8% belonged
      to the two types in adult. Our data suggest that the larger synovial folds in
      children may predispose them to an increased rate of entrapment with resultant
      edema and subluxation of the associated joint complex. This may be the cause why
      some cervical spine diseases preferentially take place in children rather than in
      adult, such as benign paroxysmal torticollis'atlantoaxial rotatory deformity and
      Grisel's syndrome.

PMID- 17022043
TI  - Right atrial aneurysm.

PMID- 17022044
TI  - An anatomic variation of the mental nerve and foramina: a case report.

PMID- 17022045
TI  - Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia.
AB  - We describe an extremely rare case of megakaryocytic blast crisis as first
      presentation of chronic myeloid leukemia. The patient had a very high platelet
      count and developed an ischemic stroke with seizures. She was treated with
      hydroxyurea, platelet apheresis, ARA-C, and idarubicin in order to obtain a
      prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The
      therapy induced a complete hematological remission with a resolution of
      neurological signs within 4 weeks.

PMID- 17022046
TI  - Superwarfarin poisoning: a report of two cases and review of the literature.
AB  - Superwarfarins are anticoagulant rodenticides similar to warfarin, but which have
      various substituted phenyl groups replacing the terminal methyl group, resulting
      in a fat-soluble, long-acting anticoagulant that is nearly 100 times more potent
      than the parent compound. Since their development, many accidental and
      intentional cases of consumption have been reported. We describe two cases of
      consumption, one related to unknown etiology, and the other related to
      utilization of the superwarfarin to potentiate a drug of abuse. The clinical
      manifestations including bleeding symptoms and abnormal coagulation assays are
      discussed. The differential diagnosis is quite broad, and includes all causes of
      vitamin K deficiency, factor deficiency or inhibitor, disseminated intravascular
      coagulation (DIC), and liver disease. Differentiating superwarfarin ingestion
      from the other causes can be quite difficult, but extremely important, as
      management requires prolonged administration of vitamin K. Other treatment
      options are discussed as well including, fresh frozen plasma (FFP), and
      recombinant factor VIIa. Finally, the significance of "lacing" drugs of abuse
      with superwarfarin to potentiate their effect is discussed, as well as the
      complications that could develop from such a habit.

PMID- 17022047
TI  - Multiple myeloma presented as acute interstitial nephritis and rheumatoid
      arthritis-like polyarthritis.
AB  - Acute interstitial nephritis and rheumatoid arthritis (RA) or RA-like
      polyarthritis are among the very rare paraneoplastic manifestations of multiple
      myeloma (MM). A 47-year-old man with acute renal failure due to interstitial
      nephritis was admitted to our university hospital and successfully treated with
      corticosteroid. He later developed a symmetric distal polyarthritis with morning
      stiffness mimicking RA. On follow-up, the patient had a rise in serum creatinine,
      hypercalcemia, anemia, and a monoclonal spike (Bence Jones protein) on the urine
      protein electrophoresis. Bone marrow biopsy demonstrated a diffuse neoplastic
      plasma cell infiltration. Diagnosis of MM was made and the patient received
      chemotherapy. After four-course chemotherapy, the patient's articular
      manifestations resolved, urine monoclonal spike disappeared, and serum creatinine
      returned to a near normal level. We hypothesize that in this case, immunologic
      hypersensitivity reactions to the light-chain molecules or other tumoral antigens
      deposited within the kidney or joint spaces, in the context of MM cytokine milieu
      may have resulted in this unusual presentation. Ultimately, clinicians and
      pathologists should consider MM in the differential diagnosis of the acute
      interstitial nephritis and RA-like polyarthritis.

PMID- 17022048
TI  - The prevalence of low hemoglobin values among new infantry recruits and nonlinear
      relationship between hemoglobin concentration and physical fitness.
AB  - There is limited information regarding the optimal hemoglobin level for physical
      activity and most studies followed relatively few participants. The object of
      this study was to assess iron storage levels in a population of healthy young
      males and their impact on physical fitness. Blood samples were drawn from 358
      consenting infantry recruits for hemoglobin, iron, ferritin, transferrin, folic
      acid, and B(12) levels. A detailed medical and nutritional history was noted.
      Recruits performed a field fitness test including a 2,000-m run. Mean hemoglobin
      was 13.8 +/- 1.0 g/dl. Level of hemoglobin lower than 14 and 12 g/dl were found
      in 53.6% and 4.5% of the recruits, respectively. Mean ferritin was 57 +/- 34
      ng/ml, with 15% of the recruits under 25 ng/ml. On multivariate analysis, after
      adjusting for pre-induction sports activity (P < 0.001), intermediate pre
      induction hemoglobin level (12-14 g/dl) was associated with significantly faster
      2,000-m running time (530 +/- 69 s, n = 176) than both the lower hemoglobin group
      (570 +/- 77 s, n = 16) and the higher hemoglobin group (552 +/- 86 s, n = 166, P
      < 0.05). The subjects in this study were non-athletic healthy young men. The high
      rate of abnormally low hemoglobin and ferritin values probably indicates a
      nutritional deficit in this population. The slower running results in the group
      with hemoglobin below 12 g/dl are in line with previous work, indicating the need
      for iron supplementation. The decrease in running ability with increased
      hemoglobin above 14 g/dl is surprising and will need further evaluation.

PMID- 17022049
TI  - Treatment and outcomes of post-transplant lymphoproliferative disease: a single
      institution study.
AB  - Post-transplant lymphoproliferative disorders (PTLD) complicate up to 10% of
      solid organ transplants. This retrospective study was conducted to review the
      PTLD experience among 2,300 recipients of solid organ or allogeneic bone marrow
      transplants from a single institution. Twenty-seven cases of PTLD were
      identified, leading to an overall incidence of 1.2%. Polymorphic B cell
      hyperplasia/lymphoma was the most common type. The median time to development of
      PTLD was 8.4 months. Ten patients had localized (stage I or II) disease, and 12
      patients presented with B symptoms. Nine patients each were treated with systemic
      chemotherapy or surgical resection as part of the initial therapy. After a median
      follow-up duration of 2.6 years, the median survival has not been reached. There
      were no late relapses of PTLD, and 17 patients remain alive. Age, sex, organ
      source, LDH, stage, presence of extranodal disease, or presentation with B
      symptoms did not influence overall survival when examined by Cox proportional
      hazard model. Thirteen patients retained their graft function throughout PTLD
      treatment. This study confirms the ability to treat a significant proportion of
      PTLD patients with chemotherapy or surgical resection (depending on
      presentation), without sacrificing graft function in those receiving
      chemotherapy.

PMID- 17022051
TI  - Role of substrate material in failure of crown-like layer structures.
AB  - The role of substrate modulus on critical loads to initiate and propagate radial
      cracks to failure in curved brittle glass shells on compliant polymeric
      substrates is investigated. Flat glass disks are used to drive the crack system.
      This configuration is representative of dental crown structures on dentin support
      in occlusal contact. Specimens are fabricated by truncating glass tubes and
      filling with epoxy-based substrate materials, with or without alumina filler for
      modulus control. Moduli ranging from 3 to 15 GPa are produced in this way.
      Critical loads for both initiation and propagation to failure increase
      monotonically with substrate modulus, by a factor of two over the data range.
      Fracture mechanics relations provide a fit to the data, within the scatter bands.
      Finite element analysis is used to determine stress distributions pertinent to
      the observed fracture modes. It is suggested that stiffer substrate materials
      offer potential for improved crown lifetime in dental practice.

PMID- 17022050
TI  - Biochemical markers of bone turnover in diagnosis of myeloma bone disease.
AB  - This study was designed to explore the value of markers of bone turnover,
      macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the
      diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and
      untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density
      matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy
      terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline
      (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase
      (BALP) were assessed in both groups. Twenty-two of the patients had bone
      involvement documented by skeletal surveys and lumbar spinal magnetic resonance
      imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly
      higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx
      levels were elevated in 90.9% of patients with MM and 40.9% of controls
      (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of
      the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were
      significantly correlated with beta2-microglobulin and lactate dehydrogenase
      levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of
      bone disease in MM, and higher than normal values suggest presence of bone
      disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha
      needs to be further investigated.

PMID- 17022052
TI  - Effects on microstrain and conversion of flowable resin composite using different
      curing modes and units.
AB  - The flowable resin composite, Tetric Flow, was used to measure microstrain and
      degree of conversion after hardening with each of three curing machines:
      XL3000(XL) for 10, 20, 30, and 40 s; Optilux 501 using conventional mode (OC) for
      10, 20, 30, and 40 s, as well as Optilux boost (OB, 10 s) and ramp modes (OR, 20
      s); and LEDemetron (LEDe) for 10, 20, 30, and 40 s. The emitted power density and
      spectral distribution of the three light curing units were also measured. The
      LEDe output energy spectrum was centralized between 425 and 490 nm, which
      encompasses the excited wavelength of camphorquinone. The microstrain produced by
      the curing process is as a second-degree polynomial for each light source. The OB
      microstrain was highest, while the OR microstrain was lower. The ranking in order
      of degree of monomer conversion was as follows: XL10 <or=<or= OC10 <or=<or= LED
      10 = OR = XL 20 = OC 20 = XL 30 <or=<or= LED 20 <or=<or= OC30 = LED 40 = XL 40 =
      OC40 = LED 30 <or= OB. The degree of conversion cured with OB was significant
      higher than other curing modes except OC30, OC40, LEDe30, LEDe40, and XL40. The
      conversion value of XL10 was the lowest. The LEDe produced higher conversion for
      the same emitted energy compared to the two halogen units.

PMID- 17022053
TI  - Nanoleakage and microshear bond strength in deproteinized human dentin.
AB  - This study evaluated the influence of dentin deproteinization with NaOCl on the
      microshear bond strength (microSBS) and the nanoleakage patterns of three dentin
      bonding systems (DBS). Occlusal dentin surfaces, obtained from extracted
      noncarious human molars, were divided into two experimental groups, according to
      dentin surface treatment: Group I-37% H(3)PO(4)/15s and Group II-37%
      H(3)PO(4)/15s + 10% NaOCl/1 min. The dentin surfaces were bonded with one of the
      following DBS: Scotchbond Multipurpose-SBMP, Prime & Bond NT-PB and Clearfil SE
      Bond-SE. After 1 week storage in water at 37 degrees C, the specimens were
      subjected to the microSBS test. The data were analyzed by two-way ANOVA and
      Student-Newman-Keuls' test (p = 0.05). The nanoleakage was evaluated using
      scanning electron microscopy (SEM) in backscattered electron imaging regime. No
      significant difference in microSBS between dentin treatments was found for SBMP.
      For PB, microSBS increased after NaOCl dentin treatment. SE showed a reduction in
      microSBS in deproteinized specimens. SEM analysis showed different nanoleakage
      patterns for each DBS. Irrespective of dentin treatments, all SBMP specimens
      showed nanoleakage. SE did not show nanoleakage with the two dentin treatments.
      PB showed nanoleakage within the hybrid layer only in acid-etched specimens. The
      influence of dentin deproteinization was dependent on the dentin bonding system
      formulation.

PMID- 17022054
TI  - Morphological and X-ray diffraction studies of crystalline hydroxyapatite
      reinforced polycaprolactone.
AB  - Morphological and mechanical properties of hydroxyapatite (HAP)-reinforced
      polycaprolactone (PCL) were studied. The objective was to examine how
      morphological features alter the bulk mechanical properties in our laboratory
      synthesized HAP-reinforced PCL. HAP crystals were synthesized by hydrolysis of
      mixtures of calcium and phosphate salts in the laboratory with wet chemical
      methods. The properties of the commercially available hydroxyapatite (HAP(1)) are
      compared with that of laboratory-synthesized hydroxyapatite (HAP(2)). The HAP
      crystals and composition were characterized using X-ray diffraction, scanning
      electron microscopy, transmission electron microscopy, and Fourier transform
      infrared spectrometry (FTIR). The HAP(1) and HAP(2) crystals were dispersed into
      polymers to examine the mechanical behavior of bioactive composites, and the
      interfacial interactions between the polymer and HAP crystals are addressed. The
      FTIR results confirmed that the two forms of HAP crystals are consistent in terms
      of the functional chemical groups. The wide angle X-ray diffraction study was
      performed to determine the crystallinity of the bioactive composites. It was
      observed that the crystallinty of HAP-filled PCL steadily increased as the filler
      concentration increased. Generally, HAP(2) has a particle size considerably
      smaller than HAP(1) and the composite derived had higher modulus than
      conventional HAP-filled polymers. This increase in modulus is attributed to
      better interfacial interaction. Bioresorbability tests performed on HAP particles
      found that the synthesized HAP had higher resorption rates. It is clear that the
      mechanical properties are influenced by the particle size and therefore by the
      processing method used.

PMID- 17022055
TI  - In vitro cytotoxicity of dental composites based on new and traditional
      polymerization chemistries.
AB  - The biological response to dental restorative polymer composites is mediated by
      the release of unpolymerized residual monomers. Several new composite
      formulations claim to reduce unpolymerized residual mass. The current study
      assessed the cytotoxic responses to several of these new formations and compared
      them with more traditional formulations. Our hypothesis predicted that if these
      new polymerization chemistries reduce unpolymerized residual mass, the
      cytotoxicity of these materials also should be reduced relative to traditional
      formulations. METHODS: Materials (HerculiteXRV, Premise, Filtek Supreme,
      CeramxDuo, Hermes, and Quixfil) were tested in vitro in direct contact with Balb
      mouse fibroblasts, initially, then after aging in artificial saliva for 0, 1, 3,
      5, or 8 weeks. The toxicity was determined by using the MTT assay to the estimate
      SDH activity. Knoop hardness of the materials also was measured at 0 and 8 weeks
      to determine whether surface breakdown of the materials in artificial saliva
      contributed to cytotoxic responses. RESULTS: Materials with traditional
      methacrylate chemistries (Herculite, Premise, Filtek Supreme) were severely
      (>50%) cytotoxic throughout the 8-week interval, but materials with newer
      chemistries or filling strategies (Hermes, CeramXDuo, and Quixfil) improved over
      time of aging in artificial saliva. Hermes showed the least cytotoxicity at 8
      weeks, and was statistically equivalent to Teflon negative controls. Hardness of
      the materials was unaffected by exposure to artificial saliva. CONCLUSIONS: Newer
      polymerization and filling strategies for dental composites show promise for
      reducing the release of unpolymerized components and cytotoxicity.

PMID- 17022056
TI  - Micromechanical versus chemical bonding between CoCr alloys and methacrylate
      resins.
AB  - INTRODUCTION: As adhesive systems for bonding to metals have developed in
      dentistry, considerable importance is attached to the preparation of the metal
      alloy for both mechanical and chemical bonding. Different grit sizes when
      sandblasting Cobalt Chromium (CoCr) will provide a different three-dimensional
      surface for bonding. Previous reports have shown that 4-Methacryloyloxyethyl
      trimellitic anhydride (4-Meta) resins offer high bond strengths to CoCr alloy,
      with various surface preparations providing varying bond strengths. The relevance
      of this to bond strength was assessed. OBJECTIVES: The aim of the study was to
      evaluate the importance of grit size of alumina in the preparation of CoCr alloy
      and to determine the effect on the tensile bond strength of four different
      acrylic resins to the CoCr alloy. METHODS: Ten specimens were prepared within
      each group of four resins. Four grit sizes were assessed, 50, 110, 250 microm,
      and a range from 180 to 330 microm. The specimens were tested both within one day
      of production after storing at 37 degrees C in phosphate-buffered saline for
      seven days and after thermocycling. RESULTS: Grit size resulted in a change in
      average contact surface area available for bonding. A significant difference (p <
      0.01) existed in bond strengths between each of the materials, but no significant
      difference (p = 0.0673) was determined when different grit sizes were included.
      SIGNIFICANCE: It was concluded that grit size determined the available contact
      surface area of CoCr alloy for bonding but did not determine the bond strength
      that could be achieved between acrylic resins and CoCr alloy as a result of the
      poor adaptation of the resin to the complex surface topography.

PMID- 17022057
TI  - Percutaneous vertebroplasty and kyphoplasty for the stand-alone augmentation of
      osteoporosis-induced vertebral compression fractures: present status and future
      directions.
AB  - Enormous research efforts are being expended on two minimally invasive
      procedures: percutaneous vertebroplasty (VP) and kyphoplasty (KP). The present
      report, which is a detailed critical review of VP and KP that emphasizes their
      biomechanics aspects, is divided into six parts. In the first two parts, succinct
      descriptions are given of osteoporosis-induced vertebral body (VB) compression
      fractures as the underlying pathology to be treated with VP and KP, the theory of
      VP and KP, and the techniques used in performing these procedures. Concerns about
      VP and KP, such as the high radiation exposure burden that may be imposed on both
      patient and medical personnel and extravasation of the injectable bone cement,
      are discussed in the third part. Detailed discussions of fourteen
      issues/questions, such as the extent to which VP or KP affects various
      biomechanical measures of the augmented VB and those adjacent to it and the
      appropriate volume of the cement to use, are presented in the fourth part. Ideas
      for future research, such as development of a new generation of injectable bone
      cements and identification of an appropriate animal model, are covered in the
      fifth part. The final section contains a summary of the most salient
      points/observations made in the report.

PMID- 17022058
TI  - Histological biocompatibility of new, non-absorbable glaucoma deep sclerectomy
      implant.
AB  - We performed this study to compare the intrascleral biocompatibility of three
      materials: non-absorbable hydrogel contact lens polymer, non-absorbable silicone
      rubber, and absorbable cross-linked sodium hyaluronate. Intrascleral implantation
      of three different materials was performed in 13 healthy, pigmented rabbits.
      Implants of methacrylic hydrogel, silicone rubber, and cross-linked sodium
      hyaluronate were implanted in 10, 8, and 8 eyes, respectively. The animals were
      euthanized at 7, 30, 180, and 360 days post implantation. The eyes were
      enucleated and immediately fixed in 10% buffered formalin. Semithin sections were
      cut and stained with hematoxylin-eosin. Light microscope analysis of the
      specimens was performed. The least severe inflammatory reaction was observed with
      cross-linked sodium hyaluronate implants. The number of inflammatory cells in
      proximity to methacrylic hydrogel and silicone implants at all periods of follow
      up was similar. The thickest fibrous capsule was observed with silicone implants
      (average, 28.38 +/- 11.17 microm). This area was thinner with methacrylic
      hydrogel implants (average, 14.90 +/- 5.57 microm) and was thinnest around sodium
      hyaluronate implants (average, 7.21 +/- 2.33 microm). For each type of implant,
      the wall on the conjunctival side of the fibrous capsule was significantly
      thicker than the wall on the choiroidal side. The space between the implant,
      scleral flap, and bed was filled soon after surgery with connective tissue rich
      in vessels. In our study, cross-linked sodium hyaluronate had the highest
      intrascleral biocompatibility. Although the inflammatory responses of the sclera
      to methacrylic hydrogel and silicone rubber were similar in nature, a thicker
      fibrous capsule was generated around silicone implants.

PMID- 17022059
TI  - Passivating protein coatings for implantable glucose sensors: evaluation of
      protein retention.
AB  - The long-term function of implantable biosensors is limited by the foreign-body
      reaction (FBR). Since the acute phase of the FBR involves macrophage attachment
      mediated by adsorbed fibrinogen, preadsorption, and retention of other proteins
      might reduce the FBR. The retention of preadsorbed albumin, hemoglobin, von
      Willebrand's factor, and high-molecular-weight kininogen was therefore measured
      after exposure to plasma. The retention of preadsorbed proteins after incubation
      with monocyte cultures and implantation in rats was also measured. Fibrinogen
      adsorption from plasma to the preadsorbed surfaces was also measured. Hemoglobin
      adsorption was higher than that for other proteins, and it also had the greatest
      retention after exposure to blood plasma. When surfaces preadsorbed with
      hemoglobin were incubated with monocytes, more of the hemoglobin was displaced
      than that after incubation in plasma, while still more hemoglobin was displaced
      when the surfaces were implanted in vivo. Protein preadsorption on polystyrene
      greatly reduced fibrinogen adsorption. However, polyurethane surfaces used for
      glucose sensors had low fibrinogen adsorption compared with polystyrene, and this
      low level was not further reduced by preadsorption with other proteins.
      Preadsorbed proteins on polymers appear to be removed by passive exchange and/or
      displacement by plasma proteins and by proteases released by monocytes.

PMID- 17022060
TI  - Influence of anti-washout agents on the rheological properties and injectability
      of a calcium phosphate cement.
AB  - Anti-washout-type calcium phosphate cement (aw-CPC) was prepared by introducing
      chitosan, sodium alginate, or modified starch into the powder phase of CPC,
      respectively. The results showed that these cements cannot be washed out and set
      within approximately 10-30 min even if the pastes were immersed in distilled
      water immediately and were shaken in a shaker after mixing and moulding. To our
      knowledge, it is the first report about the influence of the content of these
      anti-washout additives on the rheological properties and injectability of the
      cement. Moreover, novel approach of yield stress measurement was used to evaluate
      the injectability of the pastes. A modified starch was originally used as anti
      washout agent for CPC. This study provided a convenient way to use the injectable
      CPC with good anti-washout performance when the paste was exposed to blood. The
      aw-CPC had potential prospects for the wider applications in surgery such as
      orthopaedics, oral, and maxillofacial surgery.

PMID- 17022061
TI  - Blood cell separation using amphiphilic copolymers containing N,N
      dimethylacrylamide.
AB  - To develop leukocyte removal filters effective for whole blood, amphiphilic
      copolymers based on N,N-dimethylacrylamide were synthesized and evaluated as
      coating materials for poly(ethylene terephthalate) filters. The copolymers with
      methyl methacrylate or 2-hydroxypropyl methacrylate as a comonomer showed higher
      platelet permeation ratios (more than 90%) than that of the copolymer with n
      butyl methacrylate, though the logarithmic reductions of leukocytes by these
      copolymers were less than four. An increase in the platelet permeation for whole
      blood tended to increase the leukocyte permeation. The permeation of both
      platelets and leukocytes increased with the amount of copolymer coated on the
      filters because of the change in the physical properties such as the average pore
      size, total surface area, and total pore volume of coated filters. These results
      confirm that both the chemical and physical properties of the filters play
      important roles to control the permeation behavior.

PMID- 17022062
TI  - Influence of hernioplastic implants on male fertility in rats.
AB  - This study explored the vulnerability of the ductus deferens due to mesh induced
      inflammation and shrinkage after hernia repair in the rodent model. Two commonly
      used types of hernioplastic implants (Prolene and Vypro II) were surgically
      wrapped around the ductus deferentes on both sides in 20 juvenile and 20 adult
      Sprague-Dawley rats. Twenty male rats underwent sham surgeries as controls. After
      3 months, each male was mated with 2-3 adult females, which were subsequently
      sacrificed and oocytes or embryos were flushed and counted. Histochemical
      investigations of the implants and the ductus recovered surgically 4 weeks after
      implantation (one side) and after the fertility test (second side) were
      conducted. All groups exhibited 1-3 males with decreased or restricted fertility
      but there was no difference between groups. Histochemical analysis of the
      implants and the ductus recovered 4 weeks and 4 months after implantation
      revealed some sperm granulomes due to lesions of the spermatic cord caused by the
      implant in the Prolene group. There was no inflammatory reaction in the mucosa or
      blockage of the spermatic cord visible. Both types of hernioplastic implants
      tested in this investigation do not give an indication of a negative influence on
      male fertility in juvenile or adult rats.

PMID- 17022063
TI  - Characterization and in vivo evaluation of sol-gel derived hydroxyapatite
      coatings on Ti6Al4V substrates.
AB  - Hydroxyapatite (HAP) based coatings on titanium alloy Ti6Al4V were attempted by
      sol-gel process. Precursor sol was dip-coated onto the substrates and the
      formation of HAP as the main phase was ensured after the sintering of coatings at
      900 degrees C, as confirmed by the characterization studies involving XRD, FT-IR,
      Raman, and SEM-EDXS analysis. The biocompatibility of HAP-based coated titanium
      implants was tested by implantation studies in rabbit's tibia for a period of 8
      weeks. Bone remodelling and inflammatory responses of the implants were studied
      during the implantation period. The better tissue-implant interaction of the
      coated implants with respect to the uncoated implants was observed after a defect
      healing period of 8 weeks. A coated implant with no evidence of rejection is a
      further advantage of the sol-gel derived HAP coating.

PMID- 17022064
TI  - Polymer scaffolds with interconnected spherical pores and controlled architecture
      for tissue engineering: fabrication, mechanical properties, and finite element
      modeling.
AB  - A method is proposed in which the geometric properties of 3D scaffolds with
      application in tissue engineering can be tailored: porosity, pore size, and
      interconnection throat size. The architecture of the fabricated scaffolds is
      analyzed by scanning electron microscopy. The mechanical properties of these
      structures are discussed on the basis of compression stress-strain measurements.
      Moreover, the mechanical properties of the scaffolds are estimated by means of
      finite element modeling (FEM) in which the compression stress-strain test is
      simulated on an ideal structure based on the crystalline face centered cubic
      system. The elastic properties of the constructs are explained on the basis of
      the FEM model that supports the main mechanical conclusion of the experimental
      results: the compressive modulus in the first linear region does not depend on
      the geometric characteristics of the pore (pore size, interconnection throat
      size) but only on the total porosity of the scaffold.

PMID- 17022065
TI  - Hydroxyapatite formed on/in agarose gel induces activation of blood coagulation
      and platelets aggregation.
AB  - We reported earlier that hydroxyapatite (HA) formed on/in agarose gels
      (HA/agarose) produced by alternate soaking process is a bone-filling material
      possessing osteoconductive and hemostatic effects. This process could allow us to
      make bone-like apatite that was formed on/in organic polymer hydrogel matrices.
      Here, we investigated the mechanism of hemostasis induced by HA/agarose and found
      that HA/agarose, but not agarose or HA powder, significantly shortened activated
      partial thromboplastin time (APTT). While HA/agarose did not show significant
      platelet aggregation, it markedly enhanced adenosine diphosphate (ADP)-induced
      platelet aggregation. Moreover, Western blot analysis revealed selective
      adsorption of vitronectin onto HA/agarose. We also observed marked differences
      between HA powder and HA/agarose in their XRD patterns. The crystallinity of HA
      powder was much higher compared to that of HA/agarose. Furthermore, 50-100 nm of
      tube-form aggregations was observed in HA powder on the other hand 100-200 nm of
      particles was observed in HA/agarose by SEM observation. Thus 100-200 nm of low
      crystallized particles on the surface structure of HA/agarose may play an
      important role in hemostasis. Our results demonstrated a crucial role of
      HA/agarose in the mechanism of hemostasis and suggested a potential role for
      HA/agarose as a bone-grafting material.

PMID- 17022066
TI  - Preparation and characterization of poly(L-lactic acid)-chitosan hybrid scaffolds
      with drug release capability.
AB  - Novel poly(L-lactic acid) (PLLA)-chitosan hybrid scaffolds were developed in
      order to be used as tissue-engineering scaffolds and drug release carriers. The
      incorporation of chitosan into the PLLA porous structure allows for producing
      chitosan-based scaffold devices with interesting damping and stiffness aimed at
      being used in tissue engineering of bone or cartilage. The pore structure of the
      hybrid scaffolds was influenced by the concentration of the chitosan solution
      introduced into the PLLA scaffold. For lower concentrations, chitosan was mainly
      deposited onto the PLLA surface, whereas for higher concentration chitosan formed
      also microfibrilar structures within the pore walls of the PLLA foam that may act
      as additional soft anchorage sites for cells. Equilibrium water uptakes up to
      about 110% were achieved in 24 h. An anti-inflammatory drug, ketoprofen, was
      loaded within the chitosan component of the hybrid scaffolds by immersing the
      scaffolds in a drug-ethanol solution. The drug was released sharply within the
      initial periods ( approximately 2-4 h), but the rate decreased further, showing a
      sustained release. The drug release rate can be controlled by the chitosan
      content and cross-link densities, suggesting the effectiveness of the hybrid
      scaffold as a drug delivery system.

PMID- 17022067
TI  - Microarray-based comparative genomic hybridization analysis of Wolf-Hirschhorn
      syndrome in a fetus with deletion of 4p15.3 to 4pter.
AB  - BACKGROUND: Wolf-Hirschhorn syndrome (WHS), caused by the deletion of a segment
      in chromosome 4, is characterized by mental and developmental defects. Clinical
      manifestations of WHS include intrauterine growth restriction, failure to thrive
      in the neonatal period that is present simultaneously with hypotonia, typical
      "Greek helmet" facial appearance, cleft lip and palate, mental deficiency, and
      seizures. CASE: We present a case of WHS with prenatal conventional cytogenetics
      of 46,XY,der(4)t(4;13)(p15.3;p11.2)pat. High-resolution mapping using microarray
      based comparative genomic hybridization (array-CGH), including Affymetrix 10K
      arrays and cDNA microarrays, confirmed the loss of genes in the deleted region.
      CONCLUSIONS: The correlation between these candidate genes and the phenotypes of
      WHS may expand our understanding of the defective development caused by 4p
      deletion.

PMID- 17022068
TI  - Strategies for the prevention of microbial biofilm formation on silicone rubber
      voice prostheses.
AB  - Total laryngectomy, a surgical treatment for extensive cancer of larynx, which
      alters swallowing and respiration in patients, is followed up with a surgical
      voice restoration procedure comprising tracheoesophageal puncture techniques with
      insertion of a "voice prosthesis" to improve successful voice rehabilitation.
      However, microbial colonization is a major drawback of these devices.
      Antimicrobials are usually used to prevent the colonization of silicone rubber
      voice prostheses by microorganisms. However, long-term medication induces the
      development of resistant strains with all associated risks and the development of
      alternative prophylactic and therapeutic agents, including probiotics and
      biosurfactants, have been suggested. The inhibition of microbial growth on
      surfaces can also be achieved by several other techniques involving the
      modification of physicochemical properties of the biomaterial surface or the
      covalently binding of antimicrobial agents to the biomaterial surface. An
      overview of the different approaches investigated to date and future perspectives
      to reduce the frequent replacements of voice prostheses in laryngectomized
      patients through microbial biofilm retardation is presented and discussed.

PMID- 17022069
TI  - Modification of the natural history of adult-onset acid maltase deficiency by
      nutrition and exercise therapy.
AB  - Adult-onset acid maltase deficiency is an inherited lysosomal skeletal-muscle
      disease characterized by progressive myopathy and respiratory failure, for which
      there is no known therapy. In an uncontrolled, prospective study, we evaluated
      whether adherence to high-protein and low-carbohydrate nutrition and exercise
      therapy (NET) can slow the progressive deterioration of muscle function in this
      disease. Thirty-four patients have been treated with NET for periods of 2-10
      years (mean 4.5 +/- 2.5). Pre-NET rate of muscle function deterioration, as
      measured by the Walton scale, was compared to post-NET rate. Twenty-six patients
      were deemed to be consistently compliant with NET. Difference between pre-NET
      slope of muscle function deterioration to that of post-NET slope in compliant
      patients was -0.29 (95% CI -0.19, 0.39) (P < 0.0001). We conclude that compliance
      with NET can slow deterioration of muscle function and improve the natural
      history of adult-onset acid maltase deficiency. Muscle Nerve, 2006.

PMID- 17022070
TI  - Recurrent pancreatitis in mitochondrial cytopathy.
AB  - Diabetes mellitus and exocrine insufficiency are the commonest pancreatic
      manifestations of mitochondrial diseases. In contrast, pancreatitis has rarely
      been described in mitochondrial syndromes. We report on a patient with Kearns
      Sayre syndrome and recurrent episodes of acute pancreatitis for which no
      explanation could be found other than the associated mitochondrial dysfunction.
      Interestingly, pharmacological disruption of mitochondrial metabolism in various
      models as well as in patients can cause pancreatitis, further supporting this
      association. A diagnosis of pancreatitis should be considered in any patients
      with mitochondrial disease and recurrent abdominal pain.

PMID- 17022071
TI  - Diagnostic yield of chromosome analysis in patients with developmental delay or
      mental retardation who are otherwise nondysmorphic.
AB  - There is a standard recommendation that chromosomes be obtained in any patient
      who presents with developmental delay (DD) or mental retardation (MR) regardless
      of whether or not they have dysmorphic features. Increasingly, if patients are
      physically well-formed, the option to perform a karyotype is questioned because
      of the presumed low yield of a chromosomal abnormality. We hypothesize that
      patients with DD/MR who are non-dysmorphic do not have abnormal chromosomes at a
      rate high enough to warrant obtaining a karyotype on all patients in this
      population. A retrospective analysis of patients with DD/MR who were non
      dysmorphic was performed. The total number of subjects was 134. Of these, 120
      patients were recommended to have high-resolution chromosomes performed, among
      whom seven were lost to follow-up. In the remaining 113 patients, all had normal
      karyotypes. Three subjects were found to have fragile X syndrome, accounting for
      3% of the males. One subject had a pathological mutation in MECP2. Our yield of
      chromosome analysis in non-dysmorphic patients with DD/MR is less than that
      previously described. The role of array-comparative genomic hybridization (array
      CGH) as an auxiliary or alternative procedure in this patient population will be
      discussed.

PMID- 17022072
TI  - Oculo-oto-facial dysplasia (OOFD) versus Burn-McKeown syndrome.

PMID- 17022073
TI  - Trisomy 18: changes in sex ratio during intrauterine life.

PMID- 17022074
TI  - RE: Correspondence from Wieczorek & Gillessen-Kaesbach and Hing & Parisi.

PMID- 17022076
TI  - ADHD symptoms in children with FXS.
AB  - Parent- and teacher-report of attention-deficit/hyperactivity disorder (ADHD)
      symptoms were examined using problem behavior and DSM-IV symptom inventory
      questionnaires for 63 children with full mutation fragile X syndrome (FXS) and 56
      children without disabilities matched on mental age (MA). Prevalence rates of
      ADHD symptoms varied depending on type of measure (problem behavior or DSM-IV
      criteria), subscale (ADHD-inattentive or ADHD-hyperactive), scoring method
      (continuous T-scores or categorical scores based on DSM-IV algorithm), and rater
      (parent or teacher). Overall, 54-59% of boys with FXS met diagnostic behavioral
      criteria for either ADHD-inattentive type only, ADHD-hyperactive type only, or
      ADHD-combined type based on parent or teacher report. Boys with FXS were rated as
      having clinically high scores or met diagnostic criteria at higher rates than
      expected for the general population and had higher raw scores than their MA
      matched peers. Parent ratings of boys with FXS resulted in higher ADHD
      inattentive type and ADHD-hyperactive type T-scores than teachers. Boys who were
      rated as meeting DSM-IV criteria were more likely to be taking psychotropic
      medication and to have younger mental ages. Parents were substantially more
      likely than teachers to rate boys as meeting DSM-IV criteria for ADHD-inattentive
      type, while teachers were only slightly more likely than parents to rate boys as
      meeting DSM-IV criteria for ADHD-hyperactive type. Teachers were more likely than
      parents to rate boys as meeting DSM-IV criteria for ADHD when boys had lower
      levels of FMRP.

PMID- 17022077
TI  - Terminal 14q32.33 deletion: genotype-phenotype correlation.
AB  - We report on a female infant presenting with psychomotor retardation and facial
      dysmorphism. Cytogenetic studies showed an abnormal chromosome 14 with ectopic
      NOR sequences at the extremity of the long arm with a terminal 14q32.33 deletion.
      Review of the eight cases with pure terminal 14q32.3 deletions described to date
      documented that our observation is the smallest terminal 14q deletion ever
      reported. Thus, genotype-phenotype correlation allows us to delimit the critical
      region for mental retardation, hypotonia, epi-telecanthus, short bulbous nose,
      long philtrum, thin upper lip, and small mouth observed in 14 qter deletions to
      the subtelomeric 1.6 Mb of chromosome 14.

PMID- 17022078
TI  - Trends and racial disparities in muscular dystrophy deaths in the United States,
      1983-1998: an analysis of multiple cause mortality data.
AB  - To identify trends and patterns associated with muscular dystrophy (MD)
      associated deaths, we analyzed population-based data from death certificates in
      the Multiple Cause Mortality Files compiled by the National Center for Health
      Statistics. From 1983 to 1998, 14,499 deaths in the United States were associated
      with ICD-9 codes for MD. The mortality rate for MD in the general U.S. population
      over this time period was 0.365 per 100,000 persons per year. Stratification by
      age at death revealed a trimodal distribution with peaks at 0, 17, and 62 years.
      The male-to-female ratio varied with age at death, a pattern consistent with a
      mixture of autosomal and X-linked MDs with different prognoses. Deaths related to
      MD appeared to be equally divided between presumed autosomal and X-linked MDs.
      The mortality rate was higher in Whites than in Blacks, for both autosomal and X
      linked MDs. The median age at death was lower in Blacks than Whites for both
      males and females. Cardiac complications were more commonly noted among MD
      associated deaths in Blacks (38.9%) than Whites (28.6%). Respiratory infections
      were noted in about 20% of MD-associated deaths and were more common in winter
      than summer months. Potential reasons for the racial differences include
      differences in prevalence rates, rates of diagnosis, and reporting on death
      certificates. Additional studies are needed to resolve these issues. Challenges
      in the interpretation of these data include the lack of ICD-9 codes specific for
      individual MDs and potential recording biases in underlying cause of death and
      contributing factors. We also present a method for estimating autosomal and X
      linked contributions to the overall mortality rate of a genetically heterogeneous
      condition such as MD.

PMID- 17022079
TI  - Attitudes and beliefs of pediatricians and genetic counselors regarding testing
      and screening for CF and G6PD: implications for policy.
AB  - There is wide variability in conditions included in state newborn screening (NBS)
      panels. The American College of Medical Genetics (ACMG) was commissioned by
      Health Resources and Services Administration to develop a uniform NBS panel.
      Based on survey data, the ACMG committee proposed a panel that included cystic
      fibrosis (CF) and glucose-6-phosphate dehydrogenase deficiency (G6PD), although
      G6PD was excluded from their final recommendations. We examine the attitudes of
      pediatricians and genetic counselors concerning screening for these two
      conditions. Data were collected as part of two different studies. Koopmans and
      Ross surveyed a random sample of 600 pediatricians from four states based on
      their NBS panels. Hiraki et al. surveyed genetic counselors who were members of
      the National Society of Genetic Counselors (NSGC) listserv. For this analysis, we
      compare the health care professionals' (HCPs') attitudes toward a universal NBS
      program for CF and G6PD, and how their support is influenced by state policy and
      personal interest in testing their own children. Two hundred twenty-three
      pediatricians and 267 genetic counselors provided partial or complete responses.
      Pediatricians are more likely to support NBS for both CF (84%) and G6PD (58%)
      than genetic counselors (56%, P < 0.001 and 39%, P < 0.001, respectively). Both
      pediatricians and genetic counselors' attitudes toward screening correlate with
      interest in screening their own children (P < 0.001). Interest in CF screening
      also correlates with state policy (pediatricians, P < 0.001; genetic counselors,
      P < 0.025). The correlation of professional recommendations with state policies
      and personal preferences reinforces the need for systematic evidence-based
      reviews rather than reliance on stakeholder opinions for developing national
      guidelines.

PMID- 17022080
TI  - Sensenbrenner syndrome: a new member of the hepatorenal fibrocystic family.
AB  - Cranioectodermal dysplasia (CED, Sensenbrenner syndrome; OMIM #218330) is an
      autosomal recessive disorder reported only in 15 cases, which is characterized by
      dolichocephaly, rhizomelic dwarfism, dental and nail dysplasia, and progressive
      tubulo-interstitial nephritis (TIN) leading to end-stage renal failure. Herein,
      we describe a new patient with cranio-ectodermal dysplasia. Unlike previously
      reported cases, this 4-year-old child presented with tubulo-interstitial
      nephropathy associated with liver cystic disease and elevated liver enzymes. The
      liver biopsy demonstrated congenital hepatic fibrosis secondary to ductal plate
      malformation. The coexistence of a chronic tubulo-interstitial renal disease with
      lesions associated to malformations of the hepatic ductal plate indicates that
      CED as a new member of the congenital hepatorenal fibrocystic syndromes.

PMID- 17022082
TI  - Core binding factor beta (CBFB) haploinsufficiency due to an interstitial
      deletion at 16q21q22 resulting in delayed cranial ossification, cleft palate,
      congenital heart anomalies, and feeding difficulties but favorable outcome.
AB  - The core binding factor beta gene (CBFB), essential to bone morphogenesis, is
      located at 16q22.1. Homozygous deficiency of CBFB leads to ossification defects
      in mice. CBFB forms a heterodimer with RUNX2 (CBFA1) during embryonic bone
      development. RUNX2 mutations lead to cleidocranial dysplasia in humans. We
      describe an infant boy with an interstitial deletion of 16q21q22, delayed skull
      ossification, cleft palate, and heart anomalies who had a difficult course in
      infancy but eventually improved and is healthy. He was found to have CBFB
      haploinsufficiency, but did not have mutations in RUNX2. We suggest that 16q21q22
      deletion be considered when there are antenatal or postnatal findings of enlarged
      cranial sutures with or without cleft palate. The finding of CBFB
      haploinsufficiency in our case and the similarity of cranial ossification defects
      with a mouse model of CBFB deletion suggest a role for CBFB in cranial bone
      development in humans.

PMID- 17022081
TI  - Head circumference and height in autism: a study by the Collaborative Program of
      Excellence in Autism.
AB  - Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in
      Autism were combined to study the distribution of head circumference and
      relationship to demographic and clinical variables. Three hundred thirty-eight
      probands with autism-spectrum disorder (ASD) including 208 probands with autism
      were studied along with 147 parents, 149 siblings, and typically developing
      controls. ASDs were diagnosed, and head circumference and clinical variables
      measured in a standardized manner across all sites. All subjects with autism met
      ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of
      standardized head circumference in autism is normal in shape, and the mean,
      variance, and rate of macrocephaly but not microcephaly are increased. Head
      circumference tends to be large relative to height in autism. No site, gender,
      age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In
      addition to autism itself, standardized height and average parental head
      circumference were the most important factors predicting head circumference in
      individuals with autism. Mean standardized head circumference and rates of
      macrocephaly were similar in probands with autism and their parents. Increased
      head circumference was associated with a higher (more severe) ADI-R social
      algorithm score. Macrocephaly is associated with delayed onset of language.
      Although mean head circumference and rates of macrocephaly are increased in
      autism, a high degree of variability is present, underscoring the complex
      clinical heterogeneity of the disorder. The wide distribution of head
      circumference in autism has major implications for genetic, neuroimaging, and
      other neurobiological research.

PMID- 17022083
TI  - Calcium-binding and temperature induced transitions in equine lysozyme: new
      insights from the pCa-temperature "phase diagrams".
AB  - The most universal approach to the studies of metal binding properties of single
      site metal binding proteins, i.e., construction of a "phase diagram" in
      coordinates of free metal ion concentration-temperature, has been applied to
      equine lysozyme (EQL). EQL has one relatively strong calcium binding site and
      shows two thermal transitions, but only one of them is Ca(2+)-dependent. It has
      been found that the Ca(2+)-dependent behavior of the low temperature thermal
      transition (I) of EQL can be adequately described based upon the simplest four
      states scheme of metal- and temperature-induced structural changes in a protein.
      All thermodynamic parameters of this scheme were determined experimentally and
      used for construction of the EQL phase diagram in the pCa-temperature space.
      Comparison of the phase diagram with that for alpha-lactalbumin (alpha-LA), a
      close homologue of lysozyme, allows visualization of the differences in
      thermodynamic behavior of the two proteins. The thermal stability of apo-EQL
      (transition I) closely resembles that for apo-alpha-LA (mid-temperature 25
      degrees C), while the thermal stabilities of their Ca(2+)-bound forms are almost
      indistinguishable. The native state of EQL has three orders of magnitude lower
      affinity for Ca(2+) in comparison with alpha-LA while its thermally unfolded
      state (after the I transition) has about one order lower (K = 15M(-1)) affinity
      for calcium. Circular dichroism studies of the apo-lysozyme state after the first
      thermal transition show that it shares common features with the molten globule
      state of alpha-LA.

PMID- 17022085
TI  - Identification of new claudin family members by a novel PSI-BLAST based approach
      with enhanced specificity.
AB  - In an attempt to develop a novel strategy for the identification of new members
      of protein families by in silico approaches, we have developed a semi-automated
      procedure of consecutive PSI-BLAST (Position-Specific-Iterated Basic Local
      Alignment Search Tool) searches incorporating identificiation as well as
      subsequent validation of putative candidates. For a proof of concept study we
      chose the search for novel members of the claudin family. The initial step was an
      iterated PSI-BLAST search starting with the PMP22_Claudin domain of each known
      member of the claudin family against the human part of the RefSeq Database.
      Putative new claudin domains derived from the converged list were evaluated by a
      validating PSI-BLAST in which each sequence was assessed for finding back the
      starting set of known claudin domains. The local PSI-BLAST searches and
      validation were automated by a set of PERL scripts. With this strategy a total of
      three additional putative claudin domains in three different proteins were
      identified. One of them was subjected to further characterization and was shown
      to exhibit claudin-like features in terms of protein structure and expression
      pattern. The strategy we present is an efficient and versatile tool to identify
      novel members of domain-sharing protein families. Low rates of false positives
      achieved by inclusion of a validation step into the in silico procedure make this
      strategy particularly attractive to select candidates for subsequent labor
      intensive wet bench characterization.

PMID- 17022084
TI  - Crystal structures of vegetative soybean lipoxygenase VLX-B and VLX-D, and
      comparisons with seed isoforms LOX-1 and LOX-3.
AB  - The lipoxygenase family of lipid-peroxidizing, nonheme iron dioxygenases form
      products that are precursors for diverse physiological processes in both plants
      and animals. In soybean (Glycine max), five vegetative isoforms, VLX-A, VLX-B,
      VLX-C, VLX-D, VLX-E, and four seed isoforms LOX-1, LOX-2, LOX-3a, LOX-3b have
      been identified. In this study, we determined the crystal structures of the
      substrate-free forms of two major vegetative isoforms, with distinct enzymatic
      characteristics, VLX-B and VLX-D. Their structures are similar to the two seed
      isoforms, LOX-1 and LOX-3, having two domains with similar secondary structural
      elements: a beta-barrel N-terminal domain containing highly flexible loops and an
      alpha-helix-rich C-terminal catalytic domain. Detailed comparison of the
      structures of these two vegetative isoforms with the structures of LOX-1 and LOX
      3 reveals important differences that help explain distinct aspects of the
      activity and positional specificity of these enzymes. In particular, the shape of
      the three branches of the internal subcavity, corresponding to substrate-binding
      and O(2) access, differs among the isoforms in a manner that reflects the
      differences in positional specificities.

PMID- 17022086
TI  - Functional outcomes and donor site morbidity following circumferential
      pharyngoesophageal reconstruction using an anterolateral thigh flap and salivary
      bypass tube.
AB  - BACKGROUND: This study reports our experience with fasciocutaneous reconstruction
      of circumferential pharyngoesophageal defects using an anterolateral thigh flap
      wrapped around a salivary bypass tube. METHODS: The charts of 14 patients were
      reviewed. All patients who had reconstruction of a pharyngoesophageal defect
      using an anterolateral thigh flap with a salivary bypass tube between 2001 and
      2005 were included. RESULTS: There were 10 men and 4 women (mean age, 61 years).
      There were no fistulae reported, and the stricture rate was 14%. Eleven patients
      achieved oral diet sufficient to have the gastrostomy or jejunal tube removed.
      The patients who had tracheoesophageal puncture for voice developed functional
      speech. There were no flap losses. However, problems with salivary tube migration
      in the early cases have led to technique refinement. CONCLUSIONS: The low
      complication rates and the excellent functional outcomes make the anterolateral
      thigh flap in combination with a salivary bypass tube a viable option for
      reconstruction of these difficult defects.

PMID- 17022087
TI  - Role of mitomycin in upper digestive tract stricture.
AB  - BACKGROUND: Mitomycin C is an anti-fibroblast chemotherapeutic agent that has
      demonstrated promise in the treatment of head and neck cancer-related cervical
      stenosis. The present study investigates whether the application of mitomycin C
      at the time of dilation is both safe and effective in the treatment of head and
      neck cancer-related upper digestive tract stricture. METHODS: Twelve patients
      with progressive dysphagia and video-fluoroscopic evidence of upper digestive
      tract stricture after head and neck cancer treatment were dilated by Maloney or
      Savory dilators followed by the application of mitomycin C (0.2 mg/0.4 mL saline)
      to the stenotic segment for 5 minutes. Outcome measures included complication
      rate, improvement in baseline dietary consistency, and improvement in swallowing
      related quality of life as measured by the M. D. Anderson Dysphagia Inventory.
      RESULTS: All patients experienced improvement in their baseline dietary
      consistency (p = .002) and M. D. Anderson Dysphagia Inventory composite score (p
      = .001) after a mean follow-up time of 19 months. No complications from mitomycin
      use were observed. CONCLUSION: Mitomycin application appears to be a safe and
      potentially effective treatment for head and neck cancer-related upper digestive
      tract stricture. Given the small sample size and limited follow-up time, a
      randomized, controlled trial is needed to determine whether mitomycin application
      offers additional benefit over standard dilation therapy.

PMID- 17022088
TI  - Juvenile recurrent respiratory papillomatosis: still a mystery disease with
      difficult management.
AB  - Juvenile recurrent respiratory papillomatosis (RRP) is the most common benign
      neoplastic disease of the larynx in children and adolescents and has a
      significant impact on patients and the health care system with a cost ranging
      from $60,000 to $470,000 per patient. The aim of this paper is to review the
      current literature on RRP and summarize the recent advances. RRP is caused by
      human papillomavirus (HPV; mainly by types 6 and 11). Patients suffer from wart
      like growths in the aerodigestive tract. The course of the disease is
      unpredictable. Although spontaneous remission is possible, pulmonary spread and
      malignant transformation have been reported. Surgical excision, including new
      methods like the microdebrider, aims to secure an adequate airway and improve and
      maintain an acceptable voice. Repeated recurrences are common and thus
      overenthusiastic attempts to eradicate the disease may cause serious
      complications. When papillomas recur, old and new adjuvant methods may be tried.
      In addition, recent advances in immune system research may allow us to improve
      our treatment modalities and prevention strategies. A new vaccine is under trial
      to prevent HPV infection in women; the strongest risk factor for juvenile RRP is
      a maternal history of genital warts (transmitted from mother to child during
      delivery). Better understanding of the etiology of the disease and the knowledge
      of all available therapies is crucial for the best management of the affected
      patients.

PMID- 17022089
TI  - Transoral resection of thyroid cancer metastasis to lateral retropharyngeal
      nodes.
AB  - BACKGROUND: Lymph node metastasis from differentiated thyroid carcinoma may occur
      outside of the basins at greatest risk of spread, such as the lateral
      retropharyngeal lymph nodes. The extensive surgery of traditional approaches to
      the retropharyngeal space are rarely justified in the treatment of metastatic
      differentiated thyroid cancer. Therefore, a less invasive surgical approach is
      advantageous in resection of metastatic lateral retropharyngeal nodes. METHODS:
      To assess feasibility and safety, we report transoral excision guided by
      preoperative ultrasonography in a series of 3 consecutive patients with
      differentiated thyroid cancer metastatic to the retropharyngeal space. RESULTS:
      In all cases, the metastatic lateral retropharyngeal lymph node was successfully
      removed by transoral retropharyngotomy without complications. CONCLUSIONS: We
      advocate a transoral approach guided by preoperative ultrasonography for
      resection of differentiated thyroid cancer metastatic to the retropharyngeal
      lymph nodes. The approach is feasible, minimally invasive, and safe in achieving
      the goals in management of regionally metastatic disease.

PMID- 17022090
TI  - Association of sonographically detected calcification with thyroid carcinoma.
AB  - BACKGROUND: Calcification can be detected in both benign and malignant nodules
      and is often neglected by clinical physicians. The purpose of this study was to
      investigate the association of thyroid nodule calcification detected on
      ultrasound with thyroid carcinoma. METHODS: One hundred seven cases of thyroid
      carcinoma and 215 cases of benign thyroid nodules were selected from the records
      of inpatients of our hospital who had high-resolution ultrasonography
      preoperatively and pathologic diagnosis postoperatively between 2001 and 2004.
      The case numbers and percentage of calcification, fine stippled psammomatous
      (FSP), and non-FSP calcification in benign nodules and thyroid carcinoma, sex,
      and age groups (<45 years and >or=45 years) were retrospectively reviewed.
      Statistical analysis was performed using chi-square test and odds ratio.
      Sensitivity and specificity of calcification and FSP calcification on
      ultrasonography were also calculated. RESULTS: The incidence of calcification,
      non-FSP calcification, and FSP calcification were significantly higher in thyroid
      carcinoma than in the benign group (p < .001, p = .03, and p < .001,
      respectively). However, FSP calcification was more significant than the non-FSP
      calcification (p = .001) for predicting thyroid cancer. The incidence of non-FSP
      calcification and FSP calcification did not differ significantly between the
      sexes (p = .50 and p = .83, respectively). The relative risk of malignancy
      incidence was significantly higher in those younger than 45 years old with FSP
      calcification (p < .001). The incidence of non-FSP calcification was
      significantly higher in the older group (p = .03). The sensitivity of
      calcification and FSP calcification for the detection of malignancy was 63.55%
      and 24.30%, respectively; the specificity was 69.77% and 96.77%, respectively.
      CONCLUSIONS: The detection of calcification on ultrasonography should increase
      the clinical index of suspicion for thyroid carcinoma and alert the physician.
      FSP calcification is valuable and has a very high specificity for predicting
      thyroid carcinoma, particularly for those younger than 45 years old or with
      calcified regional lymph nodes. To increase the sensitivity for the diagnosis of
      thyroid carcinoma, tests such as fine-needle aspiration cytology should also be
      performed. The use of these modalities could result in earlier detection of
      thyroid carcinoma. The use of ultrasound to detect calcification and FSP
      calcification is as efficient as thyroid papillary macrocarcinoma in predicting
      microcarcinoma.

PMID- 17022091
TI  - A comparison of direct infusion MS and GC-MS for metabolic footprinting of yeast
      mutants.
AB  - Recent technical advances in mass spectrometry (MS) have propelled this
      technology to the forefront of methods employed in metabolome analysis. Here, we
      compare two distinct analytical approaches based on MS for their potential in
      revealing specific metabolic footprints of yeast single-deletion mutants.
      Filtered fermentation broth samples were analyzed by GC-MS and direct infusion
      ESI-MS. The potential of both methods in producing specific and, therefore,
      discriminant metabolite profiles was evaluated using samples from several yeast
      deletion mutants grown in batch-culture conditions with glucose as the carbon
      source. The mutants evaluated were cat8, gln3, ino2, opi1, and nil1, all with
      deletion of genes involved in nutrient sensing and regulation. From the analysis,
      we found that both methods can be used to classify mutants, but the
      classification depends on which metabolites are measured. Thus, the GC-MS method
      is good for classification of mutants with altered nitrogen regulation as it
      primarily measures amino acids, whereas this method cannot classify mutants
      involved in regulation of phospholipids metabolism as well as the direct infusion
      MS (DI-MS) method. From the analysis, we find that it is possible to discriminate
      the mutants in both the exponential and stationary growth phase, but the data
      from the exponential growth phase provide more physiological relevant
      information. Based on the data, we identified metabolites that are primarily
      involved in discrimination of the different mutants, and hereby providing a link
      between high-throughput metabolome analysis, strain classification, and
      physiology.

PMID- 17022092
TI  - Dual-syringe reactive electrospinning of cross-linked hyaluronic acid hydrogel
      nanofibers for tissue engineering applications.
AB  - A facile fabrication of a cross-linked hyaluronic acid (HA) hydrogel nanofibers
      by a reactive electrospinning method is described. A thiolated HA derivative,
      3,3'-dithiobis(propanoic dihydrazide)-modified HA (HA-DTPH), and poly(ethylene
      glycol) diacrylate (PEGDA) are selected as the cross-linking system. The cross
      linking reaction occurs simultaneously during the electrospinning process using a
      dual-syringe mixing technique. Poly(ethylene oxide) (PEO) is added into the
      spinning solution as a viscosity modifier to facilitate the fiber formation and
      is selectively removed with water after the electrospinning process. The
      nanofibrous structure of the electrospun HA scaffold is well preserved after
      hydration with an average fiber diameter of 110 nm. A cell morphology study on
      fibronectin (FN)-adsorbed HA nanofibrous scaffolds shows that the NIH 3T3
      fibroblasts migrate into the scaffold through the nanofibrous network, and
      demonstrate an elaborate three-dimensional dendritic morphology within the
      scaffold, which reflects the dimensions of the electrospun HA nanofibers. These
      results suggest the application of electrospun HA nanofibrous scaffolds as a
      potential material for wound healing and tissue regeneration. [image: see text]
      Laser scanning confocal microscopy demonstrates that the NIH3T3 fibroblast
      develops an extended 3D dendritic morphology within the fibronectin-adsorbed
      electrospun HA nanofibrous scaffold.

PMID- 17022093
TI  - Effects of pH of fermentation medium on biosynthesis of poly[(3-hydroxybutyrate)
      co-(3-mercaptopropionate)] by Wautersia eutropha.
AB  - A series of P(3HB-co-3MP)s with different 3MP unit content was biosynthesized by
      the fermentation of W. eutropha in a medium containing sodium gluconate and DTDP
      as carbon sources at different pH conditions ranging from pH 6.0 to 8.0. The
      P(3HB-co-3MP) samples were fractioned using the solvent/nonsolvent mixed solvent
      chloroform/heptane and the comonomer unit composition was investigated. It was
      found that W. eutropha produces P(3HB-co-3MP)s with extremely different 3MP unit
      content ranging from 3.6 to 70.0 mol-%, depending on the pH value of the
      fermentation medium. The copolyester samples produced in mild basic medium have a
      considerably narrower compositional distribution than the samples from acidic
      medium. The highest polymer yield was obtained at pH 8.0.DSC diagram for P(3HB-co
      3MP)s biosynthesized in different pH medium. [graph: see text] DSC diagram for
      P(3HB-co-3MP)s biosynthesized in different pH medium.

PMID- 17022094
TI  - Regioselective grafting of poly(ethylene glycol) onto chitosan and the properties
      of the resulting copolymers.
AB  - PEG was grafted onto chitosan regioselectively at the hydroxyl groups with
      phthaloylchitosan as an intermediate. After the graft reaction, the phthaloyl
      groups were deprotected to give chitosan-g-PEG copolymers with free amino groups.
      The chemical structure of the graft copolymers was confirmed by FT-IR, (1)H and
      (13)C NMR spectroscopy. The resulting graft copolymers showed improved thermal
      stability compared to the original chitosan, and showed a lower thermal
      transition temperature at around 185 degrees C. Chitosan-g-PEG exhibited a high
      affinity not only for aqueous acid but also for some organic solvents because of
      the presence of abundant free amino groups and PEG branches, and it exhibited
      higher hygroscopicity and moisture retention ability than chitosan. [structure:
      see text]

PMID- 17022095
TI  - Effect of the electrolyte concentration on cation binding in aqueous surfactant
      solutions.
AB  - Electrospray ionisation mass spectrometry (ESI-MS) is used for the qualitative
      and quantitative study of ion binding to interfaces. The ESI-MS measurements are
      carried out in aqueous solutions of sodium dodecyl sulphate (SDS) in the presence
      of NaCl, NH(4)ClO(4) , KCl, or Mg(ClO(4))(2) . The effect of the electrolyte
      concentration on the fractions, y(cation(+) ), of the DS(-) monomers bound to the
      cations is shown. Moreover, the binding stability of different cations with DS(-)
      monomers is determined versus the electrolyte concentration. This stability and
      the y(Na(+) ) values (the Na(+) ions derived from SDS), estimated in the presence
      of a given electrolyte, are quantitatively correlated with the electrolyte cation
      effect on the water structure. We also present calibration curves from which the
      molar concentrations of the sodium ions (derived from SDS) and of the other
      cations (derived from the electrolyte), bound to the SDS-micelle surface at a
      given electrolyte concentration, can be obtained. Besides, specific ion effects
      (Hofmeister effects) are considered for 1:1 electrolytes.

PMID- 17022096
TI  - Chirality amplification of porphyrin assemblies exclusively constructed from
      achiral porphyrin derivatives.
AB  - Two achiral porphyrin derivatives, 5,10,15,20-tetrakis(4-methoxyphenyl)-21H,23H
      porphine (TPPOMe) and 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine
      (TPPOH), were spread onto an air/water interface. The spreading films were
      transferred onto solid substrates by the Langmuir-Schaefer (LS) method. Although
      both of the porphyrin derivatives are achiral species, the transferred LS
      multilayer films shows macroscopic supramolecular chirality, which is suggested
      to be due to the spontaneous symmetry breaking that occurs at the air/water
      interface. A strong CD signal is observed from the as-deposited TPPOH LS film,
      while a relatively weak CD signal is detected from that of TPPOMe. Interestingly,
      when the TPPOMe LS film was annealed in high vacuum, a significant amplification
      of the supramolecular chirality is observed. Atomic force microscopy observations
      confirm that TPPOMe form more ordered aggregates upon annealing. It is suggested
      that the small amount of chiral assemblies formed in the as-deposited LS film
      grow into larger ones following the "sergeants and soldiers" principle during the
      annealing process.

PMID- 17022097
TI  - Serum, liver, and kidney proteomic analysis for the alloxan-induced type I
      diabetic mice after insulin gene transfer of naked plasmid through
      electroporation.
AB  - Gene therapy has been reported to be effective in treating diabetes mellitus
      (DM), while little has been found out about the functional protein changes since.
      The liver and kidney play important roles in glucose absorption, metabolism, and
      excretion. Changes in the two organs may reflect pathologic alterations during
      DM, while the serum has a direct connection with most organs and pathological
      changes. We used alloxan to induce diabetic mice, electrotranferred the insulin
      gene into their sural muscles, and discovered that their blood glucose decreased
      to normal level. Consequently, proteomic approaches were applied to evaluate
      protein changes in the liver, kidney, and serum of normal, diabetic, and gene
      transferred mice. Forty-three proteins were found either up-regulated or down
      reglulated in the liver, kidney, and serum of the alloxan-induced type I diabetic
      mice. Only five proteins in the liver, five proteins in the kidney, and seven
      proteins in the serum of diabetic mice were found to be back-regulated to normal
      levels after gene transfer. These back-regulated proteins are involved in lipid
      and glucose metabolism, associated with phosphorylation, signal transduction,
      oxidation, and immune inflammation. Our findings might promote a better
      understanding for the mechanism of DM, and provide novel targets for estimating
      the effects of gene therapy.

PMID- 17022098
TI  - Proteomic search for potential diagnostic markers and therapeutic targets for
      ovarian clear cell adenocarcinoma.
AB  - Clear cell adenocarcinoma (CCA) has a highly malignant potential in human
      epithelial ovarian cancer. The serum CA-125 is widely used as a marker for
      ovarian cancer, but the level is relatively low in CCA. Therefore, new sensitive
      biomarkers are required. In this report, we describe a promising proteomic
      analysis that is differentially expressed in CCA when compared to mucinous
      adenocarcinoma, using the ovarian cultured cell lines OVISE, OVTOKO, and MCAS.
      The disease-associated proteins were identified by 2-D differential gel
      electrophoresis (2-D DIGE) and MS. In this analysis, 18 up-regulated and 31 down
      regulated spots were observed that had at least two-fold differences in the two
      CCA cell lines than in MCAS as control cells. Some of the proteins differentially
      expressed in CCA were previously observed as alternative expression levels in
      ovarian and/or other cancers in clinical samples. In a subsequent preliminary
      differential study using surgical specimens from patients with CCA, it was
      demonstrated that the identified proteins were expressed differentially in actual
      tissues, as well as in the CCA culture cells. The results from this investigation
      show the potentiality of a proteomic approach for identifying disease-associated
      proteins, which may eventually serve as diagnostic markers or therapeutic targets
      in CCA.

PMID- 17022099
TI  - Protein expression of lymphocytes in HLA-DR transgenic pigs by a proteomic
      approach.
AB  - Matching donor and recipient human leucocyte antigen (HLA-II) could conquer cell
      mediated rejection following transplantation. Transgenic pigs carrying HLA genes
      that "humanize" porcine organs, tissues, and cells were successfully generated.
      This study further clarifies the effect of HLA-DR transgenes on lymphocyte
      protein expression, via a proteomic approach. Lymphocytes were isolated from two
      HLA-DR transgenic pigs and three nontransgenic littermates on 157 d after birth.
      Soluble protein of 1x10(7) cells was separated using 2-DE. In total, 301
      colloidal CBB-stained protein spots detected on all five 2-D gels were
      quantified. Thirty-three proteins were differentially expressed by a factor of
      1.5. These proteins were subsequently identified by MALDI-TOF MS and MALDI
      TOF/TOF MS/MS. These proteins were sorted into the following categories:
      chaperones, T-lymphocyte function, DNA/RNA processing, cytoskeleton-associated
      proteins, signal transduction, enzymes, and unknown. Previous studies have
      suggested that some of the identified proteins are associated with lymphocyte
      activation/proliferation. The identities of the unidentified spots and the
      systematic effect of these up- and down-regulated proteins on T-cell function in
      HLA-DR transgenic pigs require further exploration.

PMID- 17022100
TI  - The ROP2 family of Toxoplasma gondii rhoptry proteins: proteomic and genomic
      characterization and molecular modeling.
AB  - Four rhoptry proteins (ROP) of Toxoplasma gondii previously identified with mAb
      have been affinity purified and analyzed by MS; the data obtained allowed the
      genomic sequences to be assigned to these proteins. As previously suggested for
      some of them by antibody crossreactivity, these proteins were shown to belong to
      a family, the prototype of which being ROP2. We describe here the proteins ROP2,
      4, 5, and 7. These four proteins correspond to the most abundant products of a
      gene family that comprises several members which we have identified in genomic
      and EST libraries. Eight additional sequences were found and we have cloned four
      of them. All members of the ROP2 family contain a protein-kinase-like domain, but
      only some of them possess a bona fide kinase catalytic site. Molecular modeling
      of the kinase domain demonstrates the conservation of residues critical for the
      stabilization of the protein-kinase fold, especially within a hydrophobic segment
      described so far as transmembrane and which appears as an helix buried inside the
      protein. The concomitant synthesis of these ROPs by T. gondii tachyzoites
      suggests a specific role for each of these proteins, especially in the early
      interaction with the host cell upon invasion.

PMID- 17022101
TI  - Proteomic analysis of the mouse mammary gland is a powerful tool to identify
      novel proteins that are differentially expressed during mammary development.
AB  - After lactation, the mouse mammary gland undergoes apoptosis and tissue
      remodelling as the gland reverts to its prepregnant state. This complex change
      was investigated using 2-DE. An integrated database was produced from lactation
      and involution proteomes. Forty-four molecular cluster indexes (MCIs) that showed
      altered expression from lactation to involution were selected for MS analysis. Of
      these, 32 gave protein annotations, 18 of which were unequivocal proteins.
      Selected proteins were then studied across all of development, including
      pregnancy, using data integrated from another proteome database. Two proteins,
      the RNA polymerase B transcription factor 3 (BTF3) and the minichromosome
      maintenance protein 3 (MCM3), although initially selected on the basis of the
      lactation/involution criteria, had expression profiles that indicated an
      additional role in mammary development and were further analysed. BTF3, a
      transcription factor previously not described in the mammary gland, was up
      regulated strongly in pregnancy, indicating an involvement in alveolar growth.
      MCM3's expression was greatest in pregnancy and late involution, decreasing
      through lactation. Immunohistochemistry localised MCM3 to the mammary epithelium,
      where a greater proportion of cells stained than for the proliferation marker
      Ki67. MCM3 expression during lactation may identify cells that are licensed to
      repopulate the gland during cell loss in lactation and following involution.

PMID- 17022102
TI  - Identification of proteins of potential diagnostic value for bovine
      paratuberculosis.
AB  - Previously we showed that Mycobacterium paratuberculosis culture filtrates (CFs)
      contain more antigens that react with sera from infected cattle than do cellular
      extracts of the organism. The goal of the present study was to identify proteins
      of potential diagnostic value among these CF proteins. Proteins of potential
      interest were first separated by 2-DE. Roughly 240 CF protein spots were detected
      on CBB-stained gels using Phoretix 2D software. Of these, 83% reacted with serum
      from M. paratuberculosis-infected cattle in immunoblots. When bovine serum was
      absorbed with M. phlei antigens, however, only 37 of these antigenic protein
      spots were reactive. Twenty-four of these spots were selected for identification
      based on their immunoblot staining intensity and differences in pI and mass. A
      total of 14 proteins were ultimately identified by MS and BLAST searches as ModD,
      PepA, ArgJ, CobT, Antigen 85C, and nine hypothetical proteins. N-terminal peptide
      analysis of PepA, Antigen 85C, ModD, MAP1693c, MAP2168c, and MAP1022c showed that
      each protein has 27-39 amino acids that may function as a signal sequence
      suggesting they are secreted through a Sec-dependent pathway. These 14 proteins
      from M. paratuberculosis CF are strong candidates for use as antigens for
      improved serodiagnostic tests for bovine paratuberculosis.

PMID- 17022103
TI  - Optimization of paper bridge loading for 2-DE analysis in the basic pH region:
      application to the mitochondrial subproteome.
AB  - Separation of basic proteins with 2-DE presents technical challenges involving
      protein precipitation, load limitations, and streaking. Cardiac mitochondria are
      enriched in basic proteins and difficult to resolve by 2-DE. We investigated two
      methods, cup and paper bridge, for sample loading of this subproteome into the
      basic range (pH 6-11) gels. Paper bridge loading consistently produced improved
      resolution of both analytical and preparative protein loads. A unique benefit of
      this technique is that proteins retained in the paper bridge after loading basic
      gels can be reloaded onto lower pH gradients (pH 4-7), allowing valued samples to
      be analyzed on multiple pH ranges.

PMID- 17022104
TI  - Proteomic-based analysis of nuclear signaling: PLCbeta1 affects the expression of
      the splicing factor SRp20 in Friend erythroleukemia cells.
AB  - An extensive body of evidence links inositide-specific phospholipase C (PLC) to
      the nucleus and the main isoform located in the nucleus is PLCbeta(1).
      Constitutive overexpression of nuclear PLCbeta(1) has been previously shown to
      inhibit Friend erythroleukemia cells differentiation and to induce cell cycle
      progression targeting cyclin D3. The aim of this study was to identify new
      proteins regulated by PLCbeta(1) overexpression, given the role exerted by its
      signaling in the nucleus during cell growth and differentiation. To identify
      novel downstream effectors of nuclear PLCbeta(1)-dependent signaling in Friend
      erythroleukemia cells, we performed the high-resolution 2-DE-based proteomic
      analysis. Using a proteomic approach we found that SRp20, a member of the highly
      conserved SR family of splicing regulators, was down-regulated in cells
      overexpressing nuclear PLCbeta(1) as compared with wild-type cells. Reduction in
      SRp20 was confirmed by 2-D Western blotting. Moreover, we have shown that nuclear
      PLCbeta(1) is bound to the SRp20 splicing factor. Indeed, by immunoprecipitation
      and subcellular fractioning, we have demonstrated that endogenous PLCbeta(1) and
      SRp20 physically interact in the nucleus. Here we show the existence of a
      PLCbeta(1)-specific target, the splicing factor SRp20, whose expression is
      specifically down-regulated by the nuclear signaling evoked by PLCbeta(1).

PMID- 17022105
TI  - Taming a functional group: creating air-stable, chiral primary phosphanes.

PMID- 17022106
TI  - The presence of a ferrocenyl unit on an estrogenic molecule is not always
      sufficient to generate in vitro cytotoxicity.
AB  - We recently reported the dual (antihormonal and cytotoxic) functionality of
      ferrocifens, which are organometallic complexes derived from hydroxytamoxifen,
      the standard molecule in the treatment of hormone-dependent breast cancers. To
      test the hypothesis that the presence of a ferrocenyl substituent on molecules
      with an affinity for the estrogen receptor is sufficient to give them cytotoxic
      properties in vitro, we prepared complexes derived from estradiol with a
      ferrocenyl substituent at positions 7alpha and 17alpha. The complexes thus
      obtained retain a satisfactory level of affinity for the estrogen receptor (RBA
      values higher than 12 %). At low concentrations (0.1-1 microM) the complexes show
      an estrogenic effect in vitro equivalent to that of estradiol on hormone
      dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone
      independent (MDA-MB-231) breast cancer cells. At high concentrations (up to 50
      microM) the 17alpha-ethynylferrocenyl estradiol and 7alpha-ferrocenylmethylthio
      estradiol become cytotoxic (IC(50)=13.2 microM and 18.8 microM, respectively)
      while the 17alpha-ferrocenylestradiol remains non toxic. The low toxicity of
      these compounds support our hypothesis that electronic communication between the
      ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key
      parameter in the generation of cytotoxic effects at submicromolar concentrations.

PMID- 17022107
TI  - The 'natural' endpoint of dementia: death from cachexia or dehydration following
      palliative care?
AB  - OBJECTIVES: To investigate the causes of death in nursing home patients with
      dementia, and to compare causes of death in patients who survive until the final
      phase of dementia with those who die before reaching that phase, adjusted for
      potential confounders. DESIGN: Observational analysis of a cohort of patients
      with a prospective follow-up. SETTING: Psychogeriatric nursing home 'Joachim en
      Anna' in Nijmegen, the Netherlands. PARTICIPANTS: Eight hundred and ninety
      dementia patients admitted between 1980 and 1989. All patients were followed
      until death. MEASUREMENTS: The final phase of dementia was defined as total
      impairment on 20 items of a functional status questionnaire. Immediate causes of
      death (part 1a of the Dutch death certificate) were classified by the
      International Classification of Health Problems in Primary Care. RESULTS: The
      three most important reported immediate causes of death were cachexia/dehydration
      (35.2%), cardio-vascular disorders (20.9%) and acute pulmonary diseases (20.1%),
      mainly pneumonia. Cachexia/dehydration was particularly common as a cause of
      death of patients who survived to the final phase (53.2%); survival to the final
      phase of dementia was an independent predictor of cachexia/dehydration as an
      immediate cause of death with reference to cardiovascular disorders in
      multinomial regression adjusted for age at death, gender, and type of dementia.
      CONCLUSION: Patients who survive to the final phase of dementia are more likely
      to die from cachexia or dehydration than those who die before. The findings
      contribute to a debate on what should be reported as the immediate cause of death
      in dementia including perspectives from a palliative care viewpoint.

PMID- 17022108
TI  - High interleukin-6 plasma levels are associated with functional impairment in
      older patients with vascular dementia.
AB  - In older individuals, inflammatory mechanisms have been linked to the
      pathogenesis of both dementia and functional impairment. In this cross-sectional
      study we have investigated the possible association between some markers of
      systemic inflammation and functional status, in a sample of one hundred and forty
      older demented patients including 60 patients with late onset Alzheimer's disease
      (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by
      Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total
      autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6,
      Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among
      the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p <
      0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to
      II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple
      regression analysis, IL-6 was associated with BI in the whole sample and in VD,
      but not in LOAD, independent of age, gender, smoking, alcohol consumption,
      hypertension, diabetes, coronary heart disease, previous stroke, and mini mental
      state examination score. Our study suggests the existence of an independent and
      negative relationship between IL-6 plasma levels and functional status in older
      individuals with vascular dementia. This finding might contribute to explain the
      'excess of disability' phenomenon described in older demented patients.

PMID- 17022109
TI  - Comparison of the diagnostic accuracy of the Cognitive Performance Scale (Minimum
      Data Set) and the Mini-Mental State Exam for the detection of cognitive
      impairment in nursing home residents.
AB  - OBJECTIVE: To compare the diagnostic accuracy of an outcome measurement scale of
      the Minimum Data Set of the Resident Assessment Instrument for nursing homes
      (MDS/RAI-NH), the Cognitive Performance Scale (CPS) and the Mini-Mental State
      Exam (MMSE) for the detection of cognitive impairment. The Cambridge Examination
      for Mental Disorders of the Elderly--Revised (CAMDEX-R) was used as the reference
      standard. STUDY DESIGN AND SETTING: This study was part of a larger prospective
      study (QUALIDEM) involving a diagnostic procedure and two-year follow-up on the
      quality of primary care for demented patients. CAMDEX-R and MDS/RAI-NH were
      administered to 198 residents, aged 65 or more, living in 42 low and high care
      institutions for aged people. MAIN OUTCOME MEASURES: Indicators of diagnostic
      accuracy: sensitivity, specificity, predictive values, likelihood ratios, odds
      ratio and area under receiver operating characteristics curve (AUC). RESULTS: The
      CAMDEX-based prevalence of cognitive impairment was 75%. The diagnostic values of
      a CPS score of two or more for the detection of cognitive impairment were:
      sensitivity = 0.81; specificity = 0.80; PPV = 0.92; NPV = 0.57. The diagnostic
      values of a MMSE score of less than or equal 23 were: sensitivity = 0.97;
      specificity = 0.59; PPV = 0.88; NPV = 0.85. For CPS, the area under the receiver
      operating characteristic (ROC) curve was 0.87 (95% CI, 0.81-0.91), and not
      significantly different (p = 0.63) from the MMSE score, 0.88 (0.83-0.93).
      CONCLUSIONS: CPS and MMSE demonstrated similar performance to detect cognitive
      impairment in nursing home residents.

PMID- 17022110
TI  - Parallel PTS systems.

PMID- 17022112
TI  - Diversity for diversity's sake.

PMID- 17022111
TI  - Simple analytical expression for the extent of transcellular diffusion gradients.
      Addendum to "Stationary diffusion gradients..." [J. Theor. Biol. 224, 385-397
      (2003)].

PMID- 17022113
TI  - HIV treatment regimens can benefit refugees.

PMID- 17022114
TI  - New York senators oppose HIV funding changes.

PMID- 17022115
TI  - SSI. Disability benefits denied HIV-positive man.

PMID- 17022116
TI  - HIV drugs. Drug breakthroughs announced at International AIDS conference.

PMID- 17022117
TI  - Testing. Veterans study: rapid tests effective tool in HIV/AIDS war.

PMID- 17022118
TI  - Disability. Benefits denied HIV-positive Boy Scout employee.

PMID- 17022119
TI  - Prisons. Court: double-ceiling HIV-positive inmates is constitutional.

PMID- 17022121
TI  - Prevention. Church leaders support condoms, alternatives to ABC.

PMID- 17022120
TI  - Prisons. Long hair ban upheld in light of HIV, disease exposure.

PMID- 17022122
TI  - Trans fat begone!

PMID- 17022123
TI  - Insulin therapy for type 2 diabetes. Why it's often necessary.

PMID- 17022124
TI  - Treating gastroparesis.

PMID- 17022125
TI  - Bariatric surgery. Lifestyle changes for before and after.

PMID- 17022126
TI  - Eating across America. Cuisine of the Pacific Northwest.

PMID- 17022127
TI  - Sports & fitness. The great blood glucose balancing act.

PMID- 17022128
TI  - Strategies for weight management.

PMID- 17022129
TI  - Diabetes resources. Resources for the newly diagnosed.

PMID- 17022130
TI  - Supermarket smarts. Pasta.

PMID- 17022131
TI  - Diabetes basics. Navigating your way to optimal health.

PMID- 17022132
TI  - Diabetes quiz. How much do you know about heart attacks?

PMID- 17022133
TI  - Alcoholism clinical trials.

PMID- 17022134
TI  - [Pediatric primary care. Restless children].

PMID- 17022135
TI  - Abstracts from the Tenth Scientific Conference of the Charles University, Faculty
      of Medicine and University Hospital. January 24, 2006. Hradec Kralove, Czech
      Republic.

PMID- 17022136
TI  - Napoleone Ferrara wins 2006 GM Cancer Research Award.

PMID- 17022137
TI  - Causation in biomedical sciences. Proceedings of a workshop. June 17-19, 2005.
      Puidoux, Switzerland.

PMID- 17022138
TI  - "Dr Beetroot" sidelined in South Africa.

PMID- 17022139
TI  - XVI International AIDS Conference.

PMID- 17022140
TI  - [Primary prevention of cancer from industrial and environmental exposures in
      modern society. Proceedings of a workshop, November 2004, Genova, Italy].

PMID- 17022141
TI  - How's business?

PMID- 17022142
TI  - Abstracts of the 24th Conference of the European Society for Microcirculation,
      Amsterdam, The Netherlands, August 30-September 2, 2006.

PMID- 17022143
TI  - Involvement of mismatch repair in transcription-coupled nucleotide excision
      repair.
AB  - Nucleotide excision repair (NER) is a versatile repair pathway to remove a
      variety of DNA distorting lesions. NER operate via two subpathways, that are
      global genome repair (GGR) and transcription coupled nucleotide excision repair
      (TCR). GGR removes DNA damage from the genome over all, whilst TCR is selectively
      directed to DNA lesions in the transcribed strand of expressed genes. The damage
      recognition step in GGR and TCR is also different. In GGR, the XPC-HR23B complex
      is an essential factor to recruit proteins for subsequent process. In TCR, a
      stalled RNA polymerase II is a presumed trigger to initiate TCR machinery in
      concert with Cockayne syndrome (CS) proteins. Mismatch repair (MMR) keeps
      fidelity of DNA replication through correcting replication errors. A distinctive
      feature of MMR pathway is that this repair is directed exclusively to the newly
      synthesized strand. This characteristic contributes to mediation of cytotoxity by
      methylating agents, and MMR deficient cells are more resistant to methylating
      agents than MMR proficient cells. The interaction between MMR and NER has been
      reported by several investigators. However, the most controversial problem is the
      role of MMR in TCR TCR in E. coli requires the participation of the MutS and MutL
      MMR proteins. On the contrary, TCR in yeast is independent of the yeast MutS and
      MutL homologues. To date, in mammalian cells, there are conflicting evidences for
      the association of MMR with TCR pathway. The aim of this article is to provide a
      brief overview of the recent literature on this subject.

PMID- 17022144
TI  - A new turning point in glycosphingolipid research.
AB  - Research on glycosphingolipids has advanced with the finding of their involvement
      in sphingolipidoses, blood group- and differentiation-related antigens, and
      receptors for bacteria and viruses. Recently, the molecular cloning of genes for
      the synthesis of glycosphingolipids has been performed extensively, and mice
      without sugar transferase-genes have been generated. These transferase-null mice
      have shown that the complex carbohydrate structures of glycosphingolipids are not
      essential for the embryogenesis, morphogenesis or development of animals, but
      that the accumulation of an intermediate, such as GM3 or ceramide, causes
      significant failure of neural development in knockout mice as to the GM2, GD3 and
      GlcCer synthase genes. On the other hand, the nonreducing terminal carbohydrates
      in either glycosphingolipids or glycoproteins have been confirmed to be related
      to carbohydrate-mediated phenomena using the same gene-manipulation technique,
      indicating that glycosphingolipids are some of the carriers for functionally
      important carbohydrates. Glycosphingolipids are certainly small molecules with
      hydrophobic ceramides, which carry both donor and acceptor groups of the hydrogen
      bonding region with the potential ability to interact with several proteins on
      the raft structure in biomembranes, and their dynamic movement in the membranes
      was revealed by the flip-flop regulation of their synthesis in the Golgi
      apparatus and the transformation-associated alteration in the reactivity of the
      carbohydrate moiety with several ligands. Thus, research on the functional
      significance of glycosphingolipids should be carried out again regarding their
      physicochemical properties.

PMID- 17022145
TI  - Derivation and induction of the differentiation of animal ES cells as well as
      human pluripotent stem cells derived from fetal membrane.
AB  - We succeeded in the derivation and maintenance of pluripotent embryonic stem (ES)
      cells from equine and bovine blastocysts. These cells expressed markers that are
      characteristics of mouse ES cells, namely, alkaline phosphatase, stage-specific
      embryonic antigen 1, STAT 3 and Oct 4. We confirmed the pluripotential ability of
      these cells, which were able to undergo somatic differentiation in vitro to
      neural progenitors and to endothelial or hematopoietic lineages. We were able to
      use bovine ES cells as a source of nuclei for nuclear transfer and we generated
      cloned cattle with a higher frequency of pregnancies to term than has been
      achieved with somatic cells. On the other hand, we established human fetal
      membrane derived stem cell lines by the colonial cloning techniques using
      MEMalpha culture medium containing 10 ng/ml of EGF, 10 ng/ml of LIF and 10% fetal
      bovine serum (FBS). These cells appeared to maintain normal karyotype in vitro
      and expressed markers characteristics of stem cells. Furthermore, these cells
      contributed to the formation of chimeric murine embryoid bodies and gave rise to
      all three germ layers in vitro. Results from animal ES cells and human fetal
      membrane derived stem cells clearly demonstrate that these cells might be used
      for providing different types of cells for regenerative medicine as well as used
      for targeted genetic manipulation of the genome.

PMID- 17022146
TI  - Establishment and characterization of the RMG-V cell line from human ovarian
      clear cell adenocarcinoma.
AB  - A cell line, designated as RMG-V, was established from a patient with clear cell
      adenocarcinoma of the ovary. The cell line has grown without interruption and has
      been propagated continuously by serial passaging (more than 36 times) over 5
      years. The cells are spindle-shaped, display neoplastic and pleomorphic features,
      and grow in a jigsaw puzzle-like arrangement while forming monolayers without
      contact inhibition. These cells proliferate rapidly, and the population doubling
      time is about 15.5 hours. The number of chromosomes ranges between 77 and 85,
      with a modal number of 83.

PMID- 17022147
TI  - Loss of integrin alpha3 expression associated with acquisition of invasive
      potential by ovarian clear cell adenocarcinoma cells.
AB  - Among various types of surface epithelial ovarian carcinoma, clear cell
      adenocarcinoma often has a particularly poor prognosis even when diagnosed in
      stage I. It is resistant to existing anticancer drugs and appears to have
      different biological properties to other histological types of ovarian cancer.
      The present study was conducted using cell lines derived from ovarian clear cell
      adenocarcinoma in order to identify genes associated with the acquisition of
      malignant potential by this type of cancer. Two cell lines derived from ovarian
      clear cell adenocarcinoma (RMG-I and RMG-V), with different levels of invasive
      potential in an invasion assay, were used. DNA fragments were extracted from the
      band showing differences in the level of expression by RT-PCR with fluorescent
      differential display. A total of 56 different DNA base sequences were determined
      by direct sequencing. Primers were established using these base sequences and the
      level of expression in each cancer cell line was determined by real-time PCR.
      Integrin a3, the gene of which is present on chromosome 17q, was identified. It
      was also detected by a microarray analysis as one of the molecules showing a
      different level of expression between the two cell lines. Then the pattern of
      integrin a3 expression was investigated using immunocytochemical staining, and
      was found to differ between the two cell lines. The findings obtained using these
      cell lines derived from ovarian clear cell adenocarcinoma indicate that integrin
      alpha3 may associated with the acquisition of malignant potential by clear cell
      adenocarcinoma.

PMID- 17022148
TI  - Histopathological changes of the hypophysis in malnutrition in elderly subjects.
AB  - Major objectives in forensic gerontology are physical and mental disorders during
      aging, which can be caused by various factors involving nutrition and stress,
      often accompanied by dysfunction in the neuroendocrine systems including the
      hypophysis. The objective of the present study was to investigate the
      histopathological changes in the adenohypophysis in elderly subjects using
      autopsy materials. Hypophyses with a scaphoid shape (group S: 16 males and 4
      females; mean age, 78.6 years) and a normal one (group C: 30 males and 20
      females; mean age, 65.2 years) were compared. Incidence of the scaphoid-shaped
      hypophysis mildly increased with age, being 17% in the elderly over 65 years of
      age. The weight of the pituitary gland in group S (0.42 +/- 0.1 g) was lower than
      that of group C (0.65 +/- 0.2 g). The degree of fibrosis was higher in group S
      (31.6% +/- 5.4%) than in group C (18.3% +/- 6.3%). Immunohistochemical staining
      showed no significant differences in the proportion of the ACTH cells and the TSH
      cells between the two groups (p > 0.05). However, there was an increase in the
      proportion of gonadotrophs, prolactin cells, and S-100-containing cells in group
      S and a decrease in that of GH cells (p < 0.05). These findings may be associated
      with reduced anabolic, gonadal and hepatic functions due to malnutrition.

PMID- 17022149
TI  - Establishment and characterization of a human thyroid carcinoma cell line (HOTHC)
      producing colony stimulating factor.
AB  - A cell line designated HOTHC was established from an anaplastic carcinoma (giant
      cell type) of the thyroid gland of 80-year-old woman. The HOTHC line grew rapidly
      in multilayer without contact inhibition, and more than 120 serial passages were
      made within 27 months. The cells were spindle or polygonal in shape and revealed
      neoplastic and pleomorphic features. These cells were characterized as containing
      coloid droplets and poorly developed rough-endoplasmic reticulum in the
      cytoplasm. Doubling time was about 24 hours and plating efficiency was about 70%.
      The karyotype exhibits hyperploidy and marker chromosomes, and the modal
      chromosome number ranged between 77-90. The HOTHC cells were transplanted into
      the subcutis of BALB/c nude mice and produced anaplatic carcinomas (giant cell
      type) resembling the original tumor. The HOTHC cells produced colony stimulating
      factor (CSF) and caused granulocytosis in the mice.

PMID- 17022150
TI  - New chemosensitivity test using a thermo-reversible gelation polymer for
      recurrent gynecologic cancer patients and a preliminary study of mechanisms of
      anticancer drug resistance.
AB  - OBJECTIVES: TGP (thermo-reversible gelation polymer) is a high molecular compound
      that has so-gel transmitting temperature of 221C Since solid cancer tissue grows
      in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is
      suitable for chemosensitivity assays for solid tumors. In this study, a
      chemosensitivity test using TGP was applied to recurrent gynecologic cancer
      patients in order to evaluate its utility and efficacy. In some ovarian cancer
      cases, expression of anticancer drug resistance-related proteins was also
      analyzed. METHODS: Recurrent tumor tissues were surgically obtained with informed
      consent. After these tissues were minced and incubated for 4 days with CDDP,
      mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against
      these drugs was estimated. Western blotting was performed in 8 recurrent ovarian
      cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST
      pi. RESULTS: The total evaluability rate of this assay was 90.6% (29/32).
      Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of
      3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of
      chemotherapy determined by these results was 50.0%. There were significant
      correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that
      of 5-FU and MRP 2. CONCLUSIONS: Although this was a preliminary study, the
      chemosensitivity test using this new material appears to be useful for designing
      'made-to order' salvage chemotherapy for pretreated recurrent gynecologic
      patients. In order to overcome multidrug resistance, the mechanisms of multidrug
      resistance should be further investigated.

PMID- 17022151
TI  - [The use of TachoComb for the rhinorrhea repair in pituitary transsphenoidal
      surgery].
AB  - The transsphenoidal pituitary tumors surgery is often connected with
      intraoperative rhinorrhea. This complication might be serious if occurs again in
      the postoperative period. The aim of this study is to evaluate the sella
      reconstruction methods in patients with intraoperative rhinorrhea and comparing
      of their efficiency. MATERIAL AND METHODS: In the group of 259 consecutive cases
      operated on at the Neurosurgery Department in Cracow using the transsphenoidal
      approach, in 40 occured intraoperatively observed rhinorrhea. In the 26 cases we
      used Surgicel, artificial dura or fascia and Tissucol (I group), and in 14
      TachoComb with Tissucol but in 5 also fascia or artificial dura (II group).
      RESULTS: Out of the 26 patients from the I group (without TachoComb) in 5 cases
      occurred postoperatively rhinorrhea (3-36 days after surgery). 4 patients were
      reoperated, 1 patient died due to the meningitis. 2 patients suffered from the
      visual disturbances due to the sella overpacking (7,7%), what was visualized in
      the control imaging studies. In 14 cases from the II group in 2 postoperative
      rhinorrhea was observed (in the 7 and the 30 day after operation)--14,2%. There
      were no signs of meningitis, and no fatal cases. The visual disturbances as well
      as overpacking of the sella were not observed. CONCLUSIONS: Using of the
      TachoComb in reconstructive surgery of the sella reduces the risk of the post
      operative CSF leak and eliminates the features of the sella overpacking and
      visual deterioration.

PMID- 17022152
TI  - [The use of the fibrin glue in the peripheral nerves reconstructions].
AB  - In this study we presented essential historical data about application of the
      fibrin glue in microsurgical reconstructions of the peripheral nerves. The
      technique of the preparation of the fibrin glue and the most important aspects of
      the clinical practice were described. We presented also our own experience in the
      use of the fibrin glue (Tissucol Kit firmy Baxter AG, Beriplast P firmy Behring),
      in microsurgical reconstructions of the brachial plexus and peripheral nerves.
      The basic principles of management were emphasized and a few clinical cases were
      presented. Microsurgical reconstructions of the nerves with using of the fibrin
      glue are atraumatic and don't cause inflammation and granuloma formation. These
      methods allowed to while away the time of surgical procedure and allowed to
      perform a microsurgical reconstruction in difficult conditions. Microsurgical
      reconstructions of the nerves with fibrin glue application may be used
      individually or in connection with suture materials.

PMID- 17022153
TI  - Polyoxyethylene fatty acid esters as potential promotors of transdermal
      absorption for morphine hydrochloride and sulphate.
AB  - The presence of opioid receptors mu in pathologically changed skin and mucosa
      justifies application of preparations with morphine salts to obtain topical
      analgesic activity. Numerous factors associated with the vehicle and therapeutic
      agent physiochemical properties affect the capability and rate of penetration of
      a therapeutic substance in the form of a drug into dermis. Promotors of
      transcutaneous absorption, which weaken the integrity of epidermal corneal layer
      and thus, increase therapeutic substance penetration play more and more important
      role. In this study non-ionic macromolecular surface active compounds from
      Rokacets group were suggested as potential promotors of transdermal absorption
      for morphine sulphate and hydrochloride. The aim of the study was to work out
      prescription composition of ointment with morphine salts of optimal rheological
      and morphological parameters and high pharmaceutical availability of the
      therapeutic agent (morphine sulphate, hydrochloride). Three model emulsive
      ointment vehicles were prepared and selected promoters of transdermal absorption
      were introduced into them. On the basis of the formed vehicles ointments were
      made with morphine sulphate and hydrochloride. The obtained vehicles and ointment
      preparations were subjected to rheological tests. Spreadness was determined by
      extensometric method and viscosity with digital cone-plate rheometer.
      Morphological parameters of the vehicles and ointments, such as: pH and
      pharmacopeal density were estimated. Carrying out direct diffusion from the
      surface of the preparation to acceptor fluid (to water), the amount of the
      released therapeutic substance in time function was determined by
      spectrophotometric method. The performed tests demonstrated that the investigated
      vehicles and ointments are non-Newtonian systems, viscoelastic and highly
      thixotropic. The kind of morphine salt affects the spreadness and viscosity of
      model ointments. Preparations with morphine hydrochloride have higher spreadness
      than viscosity and more alkaline pH. From among the investigated non-ionic
      surface active compounds Rokacet R-40 appeared to be the most beneficial promotor
      of transdermal absorption for both pharmacopeal morphine salts. Pharmaceutical
      availability of morphine sulphate and hydrochloride is the highest from ointments
      with its content in the vehicle prescription.

PMID- 17022154
TI  - [Computer modeling the concentration characteristics of the membrane potential
      for polymeric membrane, separated non-homogeneous electrolyte solutions].
AB  - The influence of the concentration boundary layers on membrane potential
      (deltapsis) in a single-membrane system on basis of the Kedem-Katchalsky
      equations was described in cases of horizontally mounted neutral polymeric
      membrane separates non-homogeneous (mechanically unstirred) binary electrolytic
      solutions at different concentrations. Results of calculations of deltapsis as a
      function of ratio solution concentrations (Ch/Cl) at constant values of:
      concentration Rayleigh number (Rc), concentration polarization coefficient
      (zetas) and hydrostatic pressure (deltaP) were presented. Calculations were made
      for the case where on a one side of the membrane aqueous solution of NaCl at
      steady concentration 10(-3) mol x l(-1) (Cl) was placed and on the other aqueous
      solutions of NaCl at concentrations from 10(-3) mol x l(-1) to 2 x 10(-2) mol x
      l(-1) (Ch). Their densities were greater than NaCl solution's at 10(-3) mol x l(
      1). It was shown that membrane potential depends on hydrodynamic state of a
      complex concentration boundary layer-membrane-concentration boundary layer, what
      is controlled by deltaP, Ch/Cl, Rc and zetas.

PMID- 17022155
TI  - [Computer modeling the hydrostatic pressure characteristics of the membrane
      potential for polymeric membrane, separated non-homogeneous electrolyte
      solutions].
AB  - On the basis of model equation depending the membrane potential deltapsis, on
      mechanical pressure difference (deltaP), concentration polarization coefficient
      (zetas), concentration Rayleigh number (RC) and ratio concentration of solutions
      separated by membrane (Ch/Cl), the characteristics deltapsis =
      f(deltaP)zetas,RC,Ch/Cl for steady values of zetas, RC and Ch/Cl in single
      membrane system were calculated. In this system neutral and isotropic polymeric
      membrane oriented in horizontal plane, the non-homogeneous binary electrolytic
      solutions of various concentrations were separated. Nonhomogeneity of solutions
      is results from creations of the concentration boundary layers on both sides of
      the membrane. Calculations were made for the case where on a one side of the
      membrane aqueous solution of NaCl at steady concentration 10(-3) mol x l(-1) (Cl)
      was placed and on the other aqueous solutions of NaCl at concentrations from 10(
      3) mol x l(-1) to 2 x 10(-2) mol x l(-1) (Ch). Their densities were greater than
      NaCl solution's at 10(-3) mol x l(-1). It was shown that membrane potential
      depends on hydrodynamic state of a complex concentration boundary layer-membrane
      concentration boundary layer, what is controlled by deltaP, Ch/Cl, RC and zetas.

PMID- 17022156
TI  - Study of the electromotive force of electrochemical cell with polymeric membrane
      oriented in horizontal plane.
AB  - In order to characterize processes proceeded in concentration boundary layers
      (CBLs), divided by neutral and horizontally mounted membrane, the electromotive
      force (EMF) during and after turning off mechanical stirring of aqueous KCl
      solutions was measured. The EMF was measured by means of Ag / AgCl electrodes and
      electrometer connected with a microcomputer. Aqueous solutions of KCl with fixed
      and lower concentration Cl = 10(-5) mol x l(-1) was over the membrane, while KCl
      concentration under the membrane Ch > Cl was changed. Such configuration of
      membrane system caused stable reconstruction of CBLs after turning off mechanical
      stirring of solutions in electrochemical cell. On the basis of time dependencies
      of EMF the concentration dependencies were performed and it was stated that
      dependencies of EMF = f(Ch/Cl) are nonlinear. It was found that maximal value of
      EMF, equal to 175 mV, was observed during mechanical stirring of solutions for
      Ch/Cl = 400. In order to interpret experimental results, the model of EMF changes
      in time after turning off mechanical stirring was elaborated on the basis of
      Kedem-Katchalsky model equations for transport of electrolytes through the
      membrane. The transport number of K+ ions (t+), appointed for the membrane,
      depended nonlinearly on Ch/Cl and for Ch/Cl = 50 was maximal and amounted to
      t(+max) = 0.7. Besides, concentration dependence of relaxation time of CBLs
      reconstruction after turning off mechanical stirring was appointed. For Ch/Cl <
      500, increase of Ch/Cl caused considerable decrease of relaxation time, while for
      Ch/Cl > 500 the relaxation time was small and did not change considerably with
      increase of Ch/Cl, in this range.

PMID- 17022157
TI  - Treatment of intermittent exotropia.

PMID- 17022158
TI  - What's your diagnosis? Steroid-induced glaucoma.

PMID- 17022159
TI  - The active pulley hypothesis.

PMID- 17022160
TI  - Risk factors for the development of aphakic glaucoma after congenital cataract
      surgery.
AB  - BACKGROUND: It is well-known that lensectomy surgery during the first year of
      life increases one's risk of aphakic glaucoma. However, it is controversial
      whether there is a specific time period during the first year of life after which
      performing lensectomy surgery has a lower risk of aphakic glaucoma development.
      PATIENTS AND METHODS: A retrospective chart review was performed of all patients
      seen by a pediatric glaucoma specialist from 1970 to 2003. Patients were included
      in the study if they underwent congenital cataract surgery. Cataracts were
      defined as congenital if they were identified within the first 6 months of life,
      were dominantly inherited, or were of the lamellar type. Aphakic glaucoma was
      defined as having repeated intraocular pressures > 25 mm Hg after congenital
      cataract surgery. Patients were excluded if they had any conditions that were
      independently associated with glaucoma. RESULTS: A total of 368 eyes of 258
      patients were included in the study. Of these, 216 (58.7%) eyes of 150 patients
      developed aphakic glaucoma. Risk factors of greatest significance (P < .0001)
      included having lensectomy within the first year of life and the development of
      postoperative complications. CONCLUSIONS: No specific age for lensectomy during
      the first year of life was associated with a decreased risk for development of
      aphakic glaucoma. Surgery for congenital cataracts should not be delayed if the
      only reason for delay is to prevent the development of aphakic glaucoma.

PMID- 17022161
TI  - A comparison of the effectiveness of four biostains in enhancing visualization of
      the vitreous.
AB  - PURPOSE: To compare the effectiveness of four biostains in vitreous staining as a
      means to facilitate clean anterior vitrectomy. MATERIALS AND METHODS: Four
      biostains (fluorescein, indocyanine green, trypan blue, and triamcinolone
      acetonide) were used to stain the transparent vitreous of human cadaver and
      monkey cadaver eyes. Results were compared and recorded by digital photography
      and videography. RESULTS: Of the four biostains, triamcinolone acetonide best
      highlighted the vitreous. Although fluorescein, indocyanine green, and trypan
      blue also produced acceptable vitreous staining, the surrounding ocular
      structures were slightly stained as well. CONCLUSION: All four biostains enhanced
      visualization of the vitreous. However, triamcinolone acetonide best highlighted
      the vitreous.

PMID- 17022162
TI  - The factors influencing visual development in blepharophimosis-ptosis-epicanthus
      inversus syndrome.
AB  - PURPOSE: To investigate the factors influencing visual development in
      blepharophimosis-ptosis-epicanthus inversus syndrome. MATERIALS AND METHODS: The
      study population comprised 20 patients with blepharophimosis-ptosis-epicanthus
      inversus syndrome who were referred for an oculoplastic opinion. The ocular
      examination included measurement of Snellen visual acuity, cycloplegic
      refraction, ocular movements and alignment, and the presence of amblyopia.
      Patients were treated with spectacle correction, occlusion therapy, strabismus
      surgery, and oculoplastic surgery if necessary. Minimum follow-up was 2 years.
      RESULTS: Nine (45%) patients had amblyopia; 5 (25%) of these patients had
      unilateral amblyopia and 4 (20%) had bilateral amblyopia. Six (67%) patients with
      amblyopia had a significant coexisting strabismus. A significant strabismus was
      present in 11 (55%) patients; 6 (55%) of these patients had unilateral or
      bilateral amblyopia. Patients with strabismus were more likely to have amblyopia
      than those without. A total of 14 (70%) patients had refractive error; 6 (43%) of
      these patients had amblyopia. CONCLUSIONS: Patients with blepharophimosis-ptosis
      epicanthus inversus syndrome had a high rate of amblyopia, especially bilateral
      amblyopia. Patients with strabismus were more likely to have amblyopia than those
      without. Patients also had a high incidence of refractive errors.

PMID- 17022163
TI  - Evidence against mobile pulleys on the rectus muscles and inferior oblique
      muscle: central nervous system controls ocular kinematics.
AB  - PURPOSE: To provide evidence against the existence of orbital pulleys. METHODS:
      Interpretation of magnetic resonance imaging (MRI) scans; video eye tracking;
      ocular motor nerve stimulations; and clinical observations. RESULTS: No pulleys
      or planes splitting the extraocular muscles into layers were noted on MRI scans.
      Smooth muscle does not antagonize striate muscle. There is no physiological
      evidence that human rectus pulleys shift the ocular rotational axes to attain
      commutative behavior. In the monkey and humans, the axes of rotation are not
      determined by eye position. Operations on the extraocular muscles reveal no
      pulleys. CONCLUSIONS: The somatosensory system of the central nervous system
      controls the extraocular muscles. The autonomic nervous and the hormonal systems
      control the infrastructure of the orbit vital for the function of the extraocular
      muscles. The three systems are integrated and controlled by the central nervous
      system. Neural circuits are necessary to compensate for extraocular muscle
      abnormalities. There are no pulleys.

PMID- 17022165
TI  - Iridocorneal endothelial syndrome in a child.
AB  - The iridocorneal endothelial syndrome is an important and unusual cause of
      acquired glaucoma in adults. We report its occurrence in a child who presented
      with glaucoma. The patient required glaucoma surgery, and a goniotomy and
      trabeculectomy were performed. The patient's clinical findings and the results of
      surgeries are described.

PMID- 17022164
TI  - Evidence supporting extraocular muscle pulleys: refuting the platygean view of
      extraocular muscle mechanics.
AB  - BACKGROUND: Late in the 20th century, it was recognized that connective tissue
      structures in the orbit influence the paths of the extraocular muscles and
      constitute their functional origins. Targeted investigations of these connective
      tissue "pulleys" led to the formulation of the active pulley hypothesis, which
      proposes that pulling directions of the rectus extraocular muscles are actively
      controlled via connective tissues. PURPOSE: This review rebuts a series of
      criticisms of the active pulley hypothesis published by Jampel, and Jampel and
      Shi, in which these authors have disputed the existence and function of the
      pulleys. METHODS: This article reviews published evidence for the existence of
      orbital pulleys, the active pulley hypothesis, and physiological tests of the
      active pulley hypothesis. Magnetic resonance imaging in a living subject and
      histological examination of a human cadaver directly illustrate the relationship
      of pulleys to extraocular muscles. RESULTS: Strong scientific evidence is cited
      that supports the existence of orbital pulleys and their role in ocular motility.
      The criticisms of the hypothesis have ignored mathematical truisms and strong
      scientific evidence. CONCLUSIONS: Actively control led orbital pulleys play a
      fundamental role in ocular motility. Pulleys profoundly influence the neural
      commands required to control eye movements and binocular alignment. Familiarity
      with the anatomy and physiology of the pulleys is requisite for a rational
      approach to diagnosing and treating strabismus using emerging methods.
      Conversely, approaches that deny or ignore the pulleys risk the sorts of errors
      that arise in geography and navigation from incorrect assumptions such as those
      of a flat ("platygean") earth.

PMID- 17022166
TI  - Buphthalmos following systemic steroid treatment.
AB  - Corticosteroid-induced glaucoma is a well-recognized phenomenon in adults, but
      not children. We describe an infant who developed juvenile glaucoma with
      buphthalmos while receiving systemic steroid treatment. The intraocular pressure
      normalized several months following discontinuation of treatment.

PMID- 17022167
TI  - Retinoblastoma in an eye with features of Coats' disease.
AB  - A 44-month-old girl developed retinal detachment with extensive telangiectasia
      and "light bulb" aneurysms suggestive of Coats' disease. However, underlying and
      within the retina was diffuse retinoblastoma. Diffuse infiltrative retinoblastoma
      can manifest features of Coats' disease and could lead to diagnostic confusion.

PMID- 17022168
TI  - Extraocular muscle pathway displacement in myopic strabismus fixus.

PMID- 17022169
TI  - MGOS: A resource for studying Magnaporthe grisea and Oryza sativa interactions.
AB  - The MGOS (Magnaporthe grisea Oryza sativa) web-based database contains data from
      Oryza sativa and Magnaporthe grisea interaction experiments in which M. grisea is
      the fungal pathogen that causes the rice blast disease. In order to study the
      interactions, a consortium of fungal and rice geneticists was formed to construct
      a comprehensive set of experiments that would elucidate information about the
      gene expression of both rice and M. grisea during the infection cycle. These
      experiments included constructing and sequencing cDNA and robust long-serial
      analysis gene expression libraries from both host and pathogen during different
      stages of infection in both resistant and susceptible interactions, generating
      >50,000 M. grisea mutants and applying them to susceptible rice strains to test
      for pathogenicity, and constructing a dual O. sativa-M. grisea microarray. MGOS
      was developed as a central web-based repository for all the experimental data
      along with the rice and M. grisea genomic sequence. Community-based annotation is
      available for the M. grisea genes to aid in the study of the interactions.

PMID- 17022170
TI  - Priming: getting ready for battle.
AB  - Infection of plants by necrotizing pathogens or colonization of plant roots with
      certain beneficial microbes causes the induction of a unique physiological state
      called "priming." The primed state can also be induced by treatment of plants
      with various natural and synthetic compounds. Primed plants display either
      faster, stronger, or both activation of the various cellular defense responses
      that are induced following attack by either pathogens or insects or in response
      to abiotic stress. Although the phenomenon has been known for decades, most
      progress in our understanding of priming has been made over the past few years.
      Here, we summarize the current knowledge of priming in various induced-resistance
      phenomena in plants.

PMID- 17022171
TI  - Microbial endoxylanases: effective weapons to breach the plant cell-wall barrier
      or, rather, triggers of plant defense systems?
AB  - Endo-beta-1,4-xylanases (EC 3.2.1.8) are key enzymes in the degradation of xylan,
      the predominant hemicellulose in the cell walls of plants and the second most
      abundant polysaccharide on earth. A number of endoxylanases are produced by
      microbial phytopathogens responsible for severe crop losses. These enzymes are
      considered to play an important role in phytopathogenesis, as they provide
      essential means to the attacking organism to break through the plant cell wall.
      Plants have evolved numerous defense mechanisms to protect themselves against
      invading pathogens, amongst which are proteinaceous inhibitors of cell wall
      degrading enzymes. These defense mechanisms are triggered when a pathogen-derived
      elicitor is recognized by the plant. In this review, the diverse aspects of
      endoxylanases in promoting virulence and in eliciting plant defense systems are
      highlighted. Furthermore, the role of the relatively recently discovered cereal
      endoxylanase inhibitor families TAXI (Triticum aestivum xylanase inhibitor) and
      XIP (xylanase inhibitor protein) in plant defense is discussed.

PMID- 17022172
TI  - Genetic suppressors of the Lotus japonicus har1-1 hypernodulation phenotype.
AB  - Lotus japonicus har1 mutants respond to inoculation with Mesorhizobium loti by
      forming an excessive number of nodules due to genetic lesions in the HAR1
      autoregulatory receptor kinase gene. In order to expand the repertoire of mutants
      available for the genetic dissection of the root nodule symbiosis (RNS), a screen
      for suppressors of the L. japonicus har1-1 hypernodulation phenotype was
      performed. Of 150,000 M2 plants analyzed, 61 stable L. japonicus double-mutant
      lines were isolated. In the context of the har1-1 mutation, 26 mutant lines were
      unable to form RNS, whereas the remaining 35 mutant lines carried more subtle
      symbiotic phenotypes, either forming white ineffective nodules or showing reduced
      nodulation capacity. When challenged with Glomus intraradices, 18 of the 61
      suppressor lines were unable to establish a symbiosis with this arbuscular
      mycorrhiza fungus. Using a combined approach of genetic mapping, targeting
      induced local lesions in genomics, and sequencing, all non-nodulating mutant
      lines were characterized and shown to represent new alleles of at least nine
      independent symbiotic loci. The class of mutants with reduced nodulation capacity
      was of particular interest because some of them may specify novel plant functions
      that regulate nodule development in L. japonicus. To facilitate mapping of the
      latter class of mutants, an introgression line, in which the har1-1 allele was
      introduced into a polymorphic background of L. japonicus ecotype MG20, was
      constructed.

PMID- 17022173
TI  - WtsE, an AvrE-family effector protein from Pantoea stewartii subsp. stewartii,
      causes disease-associated cell death in corn and requires a chaperone protein for
      stability.
AB  - The pathogenicity of Pantoea stewartii subsp. stewartii to sweet corn and maize
      requires a Hrp type III secretion system. In this study, we genetically and
      functionally characterized a disease-specific (Dsp) effector locus, composed of
      wtsE and wtsF, that is adjacent to the hrp gene cluster. WtsE, a member of the
      AvrE family of effector proteins, was essential for pathogenesis on corn and was
      complemented by DspA/E from Erwinia amylovora. An intact C-terminus of WtsE,
      which contained a putative endoplasmic reticulum membrane retention signal, was
      important for function of WtsE. Delivery of WtsE into sweet corn leaves by an
      Escherichia coli strain carrying the hrp cluster of Erwinia chrysanthemi caused
      water-soaking and necrosis. WtsE-induced cell death was not inhibited by
      cycloheximide treatment, unlike the hypersensitive response caused by a known Avr
      protein, AvrRxol. WtsF, the putative chaperone of WtsE, was not required for
      secretion of WtsE from P. stewartii, and the virulence of wtsF mutants was
      reduced only at low inoculum concentrations. However, WtsF was required for full
      accumulation of WtsE within the bacteria at low temperatures. In contrast, WtsF
      was needed for efficient delivery of WtsE from E. coli via the Erwinia
      chrysanthemi Hrp system.

PMID- 17022174
TI  - Molecular basis of ergosterol-induced protection of grape against botrytis
      cinerea: induction of type I LTP promoter activity, WRKY, and stilbene synthase
      gene expression.
AB  - Type I lipid transfer proteins (LTPs) are basic, 9-kDa cystein-rich proteins
      believed to be involved in plant defense mechanisms. A 2,100-bp fragment
      containing the coding region of Vitis vinifera lipid transfer protein 1 (VvLTP1)
      and 1,420-bp of its promoter region was isolated by screening a grape genomic
      library. In silico analysis revealed several putative, defense-related, cis
      regulatory elements such as W- and MYB-boxes, involved in the binding of WRKY and
      MYB transcription factors, respectively. The 5'-truncated versions of the VvLTP1
      promoter were generated, cloned in front of the beta-glucuronidase (GUS) reporter
      gene, and introduced in tobacco plants and grapevine cell suspensions using
      Agrobacterium spp. Single MYB- and the W-boxes identified on the 0.250-kbp
      fragment were sufficient to induce GUS activity in transgenic tobacco plants
      after transient expression of MYB and WRKY. Ergosterol, a nonspecific fungal
      elicitor, induced GUS activity in transgenic grapevine cell suspensions
      transformed with the 1,420- and 750-bp promoter containing a palindromic
      arrangement of two W-boxes but not the 650- or 250-bp fragment, where only one W
      box was present. Moreover, ergosterol triggered WRKY, VvLTP1, and stilbene
      synthase gene expression in grape plantlets and enhanced protection against
      Botrytis cinerea. The molecular basis of ergosterol-induced protection is
      discussed.

PMID- 17022175
TI  - Biological characterization of white line-inducing principle (WLIP) produced by
      Pseudomonas reactans NCPPB1311.
AB  - The biological activities of the lipodepsipeptides (LDP) white line-inducing
      principle (WLIP), produced by Pseudomonas reactans NCPPB1311, and tolaasin I,
      produced by R tolaasii NCPPB2192, were compared. Antimicrobial assays showed that
      both LDP inhibited the growth of fungi-including the cultivated mushrooms
      Agaricus bisporus, Lentinus edodes, and Pleurotus spp.--chromista, and gram
      positive bacteria. Assays of the two LDP on blocks of Agaricus bisporus showed
      their capacity to alter the mushrooms' pseudo-tissues though WLIP was less active
      than that of tolaasin I. Contrary to previous studies, tolaasin I was found to
      inhibit the growth of gram-negative bacteria belonging to the genera Escherichia,
      Erwinia, Agrobacterium, Pseudomonas, and Xanthomonas. The only gram-negative
      bacterium affected by WLIP was Erwinia carotovora subsp. carotovora. Both WLIP
      and tolaasin I caused red blood cell lysis through a colloid-osmotic shock
      mediated by transmembrane pores; however, the haemolytic activity of WLIP was
      greater than that of tolaasin I. Transmembrane pores, at a concentration
      corresponding to 1.5 x C50, showed a radius between 1.5 and 1.7 +/- 0.1 nm for
      WLIP and 2.1 +/- 0.1 nm for tolaasin I. The antifungal activity of WLIP together
      with the finding that avirulent morphological variants of P. reactans lack WLIP
      production suggests that WLIP may play an important role in the interaction of
      the producing bacterium P. reactans and cultivated mushrooms.

PMID- 17022176
TI  - Effects of the tomato pathogen Fusarium oxysporum f. sp. radicis-lycopersici and
      of the biocontrol bacterium Pseudomonas fluorescens WCS365 on the composition of
      organic acids and sugars in tomato root exudate.
AB  - The effects of the pathogenic fungus Fusarium oxysporum f. sp. radicis
      lycopersici and of the bacterial biocontrol strain Pseudomonas fluorescens
      WCS365, and of both microbes, on the amounts and composition of root exudate
      components of tomato plants grown in a gnotobiotic stonewool substrate system
      were studied. Conditions were selected under which introduction of F. oxysporum
      f. sp. radicis-lycopersici caused severe foot and root rot, whereas inoculation
      of the seed with P. fluorescens WCS365 decreased the percentage of diseased
      plants from 96 to 7%. This is a much better disease control level than was
      observed in potting soil. Analysis of root exudate revealed that the presence of
      F. oxysporum f. sp. radicis-lycopersici did not alter the total amount of organic
      acids, but that the amount of citric acid decreased and that of succinic acid
      increased compared with the nontreated control. In contrast, in the presence of
      the P. fluorescens biocontrol strain WCS365, the total amount of organic acid
      increased, mainly due to a strong increase of the amount of citric acid, whereas
      the amount of succinic acid decreased dramatically. Under biocontrol conditions,
      when both microbes are present, the content of succinic acid decreased and the
      level of citric acid was similar to that in the nontreated control. The amount of
      sugar was approximately half that of the control sample when either one of the
      microbes was present alone or when both were present. Analysis of the
      interactions between the two microbes grown together in sterile tomato root
      exudate showed that WCS365 inhibited multiplication of F. oxysporum f. sp.
      radicis-lycopersici, whereas the fungus did not affect the number of CFU of the
      bacterium.

PMID- 17022177
TI  - Inducible overexpression of a rice allene oxide synthase gene increases the
      endogenous jasmonic acid level, PR gene expression, and host resistance to fungal
      infection.
AB  - Many studies in dicotyledonous plants have shown that jasmonates, including
      jasmonic acid (JA) and methyl jasmonate, are important signal molecules involved
      in induced resistance to pathogen infection and insect herbivory. However, very
      little genetic and molecular evidence is available to demonstrate their role in
      host defense response of rice and other economically important monocot plants. In
      this study, we have shown that exogenous application of JA was able to activate
      defense gene expression and local induced resistance in rice seedlings against
      the rice blast fungus (Magnaporthe grisea). Furthermore, we have characterized a
      pathogen-inducible rice OsAOS2 gene (which encodes allene oxide synthase, a key
      enzyme in the JA biosynthetic pathway) and examined the role of endogenous JA in
      rice defense response through transgenic manipulation of the JA biosynthesis.
      Sequence analysis indicated that OsAOS2 contains four common domains of the
      cytochrome P450 enzyme, but does not have the signal peptide for chloroplast
      targeting. The basal level of OsAOS2 expression is very low in leaves but
      relatively high in the sheath, culm, and flower of rice plants. Interestingly,
      the expression of OsAOS2 in rice leaves can be induced significantly upon M.
      grisea infection. Transgenic rice lines carrying the OsAOS2 transgene under the
      control of a strong, pathogen-inducible PBZ1 promoter accumulated abundant OsAOS2
      transcripts and higher levels of JA, especially after the pathogen infection.
      These transgenic lines also exhibited enhanced activation of pathogenesis-related
      (PR) genes such as PR1a, PR3, and PR5 and increased resistance to M. grisea
      infection. Our results suggest that JA plays a significant role in PR gene
      induction and blast resistance in rice plants.

PMID- 17022178
TI  - Yeast increases resistance in Arabidopsis against Pseudomonas syringae and
      Botrytis cinerea by salicylic acid-dependent as well as -independent mechanisms.
AB  - Cell-wall and glucopeptide components of yeast have been reported to exhibit
      elicitor activity. The mode of action of defense activation by yeast is not known
      so far. In this study, we used the model plant Arabidopsis to investigate the
      activation of defense responses by yeast, the effect on resistance against
      different pathogens, and the mode of action. Treatment of Arabidopsis plants with
      an autoclaved yeast suspension induced the expression of systemic acquired
      resistance-related genes and accumulation of the phytoalexin camalexin. Symptom
      development and bacterial growth after infection with a virulent strain of the
      pathogen Pseudomonas syringae was reduced in yeast-pretreated plants. No
      protection was detectable in mutants affected in the salicylate pathway, while
      mutants in the jasmonate or camalexin pathway were protected by yeast, indicating
      that the salicylate pathway is necessary for the yeast-induced resistance against
      P. syringae. Yeast also reduced symptom development after challenge with Botrytis
      cinerea. This protection was detectable in all mutants tested, indicating that it
      is independent of the salicylate, jasmonate, and camalexin pathway.

PMID- 17022179
TI  - [Who is best suited for medical career? A combination of admission criteria for
      better selection].

PMID- 17022180
TI  - [Misleading about cartilage transplantation].

PMID- 17022181
TI  - [High blood glucose in diabetics a risk factor in acute myocardial infarction.
      Intensive insulin therapy--an interesting but not functioning idea].

PMID- 17022182
TI  - [Thunderclap headache--mostly a benign condition. Investigation guidelines-
      subarachnoid hemorrhage should be excluded].

PMID- 17022183
TI  - [Still uncertainty about the usefulness of perioperative beta-blockade.
      Conclusive studies concerning patients with cardiovascular risk factors not
      available].

PMID- 17022184
TI  - [Peripheral arterial disease in primary health care. Occurrence and care].

PMID- 17022185
TI  - [Virus-like particles as cancer vaccine. Great expectations--not only for
      papillomavirus associated cancer].

PMID- 17022186
TI  - [Traumatic tracheobronchial rupture in children--an unusual and life-threatening
      injury].

PMID- 17022187
TI  - [Stilnoct and sleepwalking].

PMID- 17022188
TI  - [Abortion tourism and human dignity].

PMID- 17022189
TI  - [Future of forensic psychiatry: don't underestimate the penal code principles!].

PMID- 17022190
TI  - [The Swedish Institute of Infectious Disease Control starts a registry for follow
      up of vaccination against human papillomavirus].

PMID- 17022191
TI  - [Insufficient controllable, measuring data in a debate article on alcohol
      ignition interlock].

PMID- 17022192
TI  - Evaluation of a barrier dental sealant in dogs.

PMID- 17022193
TI  - Collagen fiber architecture of the periodontal ligament in equine cheek teeth.
AB  - The objective of this study was to examine the spatial arrangement of the fiber
      apparatus of the equine periodontium which is supposed to meet two contrary
      requirements: (1) to attach the tooth firmly and elastically to the alveolar
      bone; and, to be appropriately remodeled and reconstructed in order to facilitate
      the prolonged eruption of the tooth. Specimens of periodontal ligament were
      obtained from the buccal and lingual/palatal aspects of the first molars from the
      maxilla and mandible of 12 horses. The animals were assigned to three age groups.
      Histological sections were prepared from three specific horizontal levels of the
      periodontal ligament and examined with conventional and polarized-light
      microscopy. At the gingival level, collagen fascicles (diameter > 200 microm)
      were densely packed. Their spatial alignment was the same in all age groups. The
      architecture of the collagen fiber apparatus differed at the middle and apical
      levels in the three age groups. There was a clear distinction between fibers,
      bundles, and fascicles. Bundling of collagen fibers, density of the fiber
      arrangement, and collagen fascicles with an alveolo-cemental orientation
      increased with age. The collagen fiber apparatus of the equine periodontal
      ligament is highly adaptive, responding continuously to the dynamic changes in
      the periodontal environment. Site-specific arrangements and age-dependent
      structural variations are assumed to maintain tooth support as the reserve crown
      gradually decreases in length with progressive dental attrition. Most of the age
      dependent changes to the periodontal ligament in teeth examined in this study
      occurred at the apical level. The apical region of young teeth had no periodontal
      attachment, while the roots of older teeth were firmly attached to the alveolus.
      When evaluating periodontal ligament development, the individual tooth's 'dental
      age' should be considered rather than the animal's age to account for individual
      tooth eruption times.

PMID- 17022194
TI  - Root canal treatment in dogs and cats.

PMID- 17022195
TI  - Greater palatine island axial pattern flap for repair of oronasal fistula related
      to eosinophilic granuloma.
AB  - A Greyhound presented with eosinophilic granuloma lesions of the soft palate and
      oronasal fistula. Since other siblings had been known to also have oral
      eosinophilic granuloma, it was suspected that the dog reported here had a
      familial predisposition to develop the disease. Preoperative medical management
      consisting of anti-inflammatory and immunosuppressive therapy was required before
      surgical repair of the oronasal fistula. Multiple surgical techniques, including
      a greater palatine island axial pattern flap, were used to repair the oronasal
      fistula.

PMID- 17022196
TI  - Surgical extraction of impacted teeth in a dog.

PMID- 17022197
TI  - Bur basics.

PMID- 17022198
TI  - Mucoperiosteal flap for extraction of multiple teeth in the maxillary quadrant of
      the cat.

PMID- 17022199
TI  - Point/Counterpoint. The best radiotherapy for the treatment of prostate cancer
      involves hypofractionation.

PMID- 17022200
TI  - Automated lung segmentation of diseased and artifact-corrupted magnetic resonance
      sections.
AB  - Segmentation of the lungs within magnetic resonance (MR) scans is a necessary
      step in the computer-based analysis of thoracic MR images. This process is often
      confounded by image acquisition artifacts and disease-induced morphological
      deformation. We have developed an automated method for lung segmentation that is
      insensitive to these complications. The automated method was applied to 23
      thoracic MR scans (413 sections) obtained from 10 patients. Two radiologists
      manually outlined the lung regions in a random sample of 101 sections (n=202
      lungs), and the extent to which disease or artifact confounded lung border
      visualization was evaluated. Accuracy of lung regions extracted by the automated
      segmentation method was quantified by comparison with the radiologist-defined
      lung regions using an area overlap measure (AOM) that ranged from 0 (disjoint
      lung regions) to 1 (complete overlap). The AOM between each observer and the
      automated method was 0.82 when averaged over all lungs. The average AOM in the
      lung bases, where lung segmentation is most difficult, was 0.73.

PMID- 17022201
TI  - Radiation induced currents in parallel plate ionization chambers: measurement and
      Monte Carlo simulation for megavoltage photon and electron beams.
AB  - Polarity effects in ionization chambers are caused by a radiation induced
      current, also known as Compton current, which arises as a charge imbalance due to
      charge deposition in electrodes of ionization chambers. We used a phantom
      embedded extrapolation chamber (PEEC) for measurements of Compton current in
      megavoltage photon and electron beams. Electron contamination of photon beams and
      photon contamination of electron beams have a negligible effect on the measured
      Compton current. To allow for a theoretical understanding of the Compton current
      produced in the PEEC effect we carried out Monte Carlo calculations with a
      modified user code, the COMPTON/ EGSnrc. The Monte Carlo calculated COMPTON
      currents agree well with measured data for both photon and electron beams; the
      calculated polarity correction factors, on the other hand, do not agree with
      measurement results. The conclusions reached for the PEEC can be extended to
      parallel-plate ionization chambers in general.

PMID- 17022202
TI  - Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship
      between aerobic and hypoxic linear-quadratic (LQ) model parameters.
AB  - The poor treatment prognosis for tumors with high levels of hypoxia is usually
      attributed to the decreased sensitivity of hypoxic cells to ionizing radiation.
      Mechanistic considerations suggest that linear quadratic (LQ) survival model
      radiosensitivity parameters for hypoxic (H) and aerobic (A) cells are related by
      alphaH = alphaA/oxygen enhancement ratio (OER) and
      (alpha/beta)H=OER(alpha/beta)A. The OER parameter may be interpreted as the ratio
      of the dose to the hypoxic cells to the dose to the aerobic cells required to
      produce the same number of DSBs per cell. The validity of these expressions is
      tested against survival data for mammalian cells irradiated in vitro with low-
      and high-LET radiation. Estimates of hypoxic and aerobic radiosensitivity
      parameters are derived from independent and simultaneous least-squares fits to
      the survival data. An external bootstrap procedure is used to test whether
      independent fits to the survival data give significantly better predictions than
      simultaneous fits to the aerobic and hypoxic data. For low-LET radiation,
      estimates of the OER derived from the in vitro data are between 2.3 and 3.3 for
      extreme levels of hypoxia. The estimated range for the OER is similar to the
      oxygen enhancement ratios reported in the literature for the initial yield of
      DSBs. The half-time for sublethal damage repair was found to be independent of
      oxygen concentration. Analysis of patient survival data for cervix cancer
      suggests an average OER less than or equal to 1.5, which corresponds to a pO2 of
      5 mm Hg (0.66%) in the in vitro experiments. Because the OER derived from the
      cervix cancer data is averaged over cells at all oxygen levels, cells irradiated
      in vivo under extreme levels of hypoxia (<0.5 mm Hg) may have an OER
      substantially higher than 1.5. The reported analyses of in vitro data, as well as
      mechanistic considerations, provide strong support for the expressions relating
      hypoxic and aerobic radiosensitivity parameters. The formulas are also useful for
      the analysis of clinical data because the number of radiosensitivity parameters
      that need to be determined is reduced from four to three without a substantial
      decrease in the ability of the LQ to accurately predict the surviving faction.
      The relationships among radiosensitivity parameters imply that the dose to the
      hypoxic subvolume of the tumor needs to be escalated by a factor of the OER to
      achieve the same level of tumor control as in well oxygenated tumor regions.

PMID- 17022203
TI  - Relation of external surface to internal tumor motion studied with cine CT.
AB  - The accuracy of delivering gated-radiation therapy to lung tumors using an
      external respiratory surrogate relies on not only interfractional and
      intrafractional reproducibility, but also a strong correlation between external
      motion and internal tumor motion. The purpose of this work was to use the cine
      images acquired by four-dimensional computed tomography acquisition protocol to
      study the relation between external surface motion and internal tumor motion. The
      respiratory phase information of tumor motion and chest wall motion was measured
      on the cine images using a proposed region-of-interest (ROI) method and compared
      to measurement of an external respiratory monitoring device. On eight lung
      patient data sets, the phase shifts were measured between (1) the signal of a
      real-time positioning-management (RPM) respiratory monitoring device placed in
      the abdominal region and four surface locations on the chest wall, (2) the RPM
      signal in the abdominal region and tumor motions, and (3) chest wall surface
      motions and tumor motions. Respiratory waveforms measured at different surface
      locations during the same respiratory cycle often varied and had significant
      phase shifts. Seven of the 8 patients showed the abdominal motion leading chest
      wall motion. The best correlation (smallest phase shift) was found between the
      abdominal motion and the superior-inferior (S-I) tumor motion. A wide range of
      phase shifts was observed between external surface motion and tumor anterior
      posterior (A-P)/lateral motion. The result supported the placement of the RPM
      block in the abdominal region and suggested that during a gated therapy utilizing
      the RPM system, it is necessary to place the RPM block at the same location as it
      is during treatment simulation in order to reduce potential errors introduced by
      the position of the RPM block. Correlations between external motions and
      lateral/A-P tumor motions were inconclusive due to a combination of patient
      selection and the limitation of the ROI method.

PMID- 17022204
TI  - Study of noise propagation and the effects of insufficient numbers of projection
      angles and detector samplings for iterative reconstruction using planar-integral
      data.
AB  - A rotating slat collimator can be used to acquire planar-integral data. It
      achieves higher geometric efficiency than a parallel-hole collimator by accepting
      more photons, but the planar-integral data contain less tomographic information
      that may result in larger noise amplification in the reconstruction. Lodge
      evaluated the rotating slat system and the parallel-hole system based on noise
      behavior for an FBP reconstruction. Here, we evaluate the noise propagation
      properties of the two collimation systems for iterative reconstruction. We extend
      Huesman's noise propagation analysis of the line-integral system to the planar
      integral case, and show that approximately 2.0(D/dp) SPECT angles, 2.5(D/dp) self
      spinning angles at each detector position, and a 0.5dp detector sampling interval
      are required in order for the planar-integral data to be efficiently utilized.
      Here, D is the diameter of the object and dp is the linear dimension of the
      voxels that subdivide the object. The noise propagation behaviors of the two
      systems are then compared based on a least-square reconstruction using the ratio
      of the SNR in the image reconstructed using a planar-integral system to that
      reconstructed using a line-integral system. The ratio is found to be proportional
      to the square root of F/D, where F is a geometric efficiency factor. This result
      has been verified by computer simulations. It confirms that for an iterative
      reconstruction, the noise tradeoff of the two systems is not only dependent on
      the increase of the geometric efficiency afforded by the planar projection
      method, but also dependent on the size of the object. The planar-integral system
      works better for small objects, while the line-integral system performs better
      for large ones. This result is consistent with Lodge's results based on the FBP
      method.

PMID- 17022205
TI  - Multiview-based computer-aided detection scheme for breast masses.
AB  - In this study, we developed and tested a new multiview-based computer-aided
      detection (CAD) scheme that aims to maintain the same case-based sensitivity
      level as a single-image-based scheme while substantially increasing the number of
      masses being detected on both ipsilateral views. An image database of 450 four
      view examinations (1800 images) was assembled. In this database, 250 cases
      depicted malignant masses, of which 236 masses were visible on both views and 14
      masses were visible only on one view. First, we detected suspected mass regions
      depicted on each image in the database using a single-image-based CAD. For each
      identified region (with detection score > or = 0.55), we then identified a
      matching strip of interest on the ipsilateral view based on the projected
      distance to the nipple along the centerline. By lowering CAD operating threshold
      inside the matching strip, we searched for a region located inside the strip and
      paired it with the original region. A multifeature-based artificial neural
      network scored the likelihood of the paired "matched" regions representing true
      positive masses. All single (unmatched) regions except for those either with very
      high detection scores (> or = 0.85) or those located near the chest wall that
      cannot be matched on the other view were discarded. The original single-image
      based CAD scheme detected 186 masses (74.4% case-based sensitivity) and 593 false
      positive regions. Of the 186 identified masses, 91 were detected on two views
      (48.9%) and 95 were detected only on one view (51.1%). Of the false-positive
      detections, 54 were paired on the ipsilateral view inside the corresponding
      matching strips and the remaining 485 were not, which represented 539 case-based
      false-positive detections (0.3 per image). Applying the multiview-based CAD
      scheme, the same case-based sensitivity was maintained while cueing 169 of 186
      masses (90.9%) on both views and at the same time reducing the case-based false
      positive detection rate by 23.7% (from 539 to 411). The study demonstrated that
      the new multiview-based CAD scheme could substantially increase the number of
      masses being cued on two ipsilateral views while reducing the case-based false
      positive detection rate.

PMID- 17022206
TI  - A simple method for labeling CT images with respiratory states.
AB  - A method is described for labeling CT images with their respiratory state by a
      needle, connected to the patient's chest/abdomen. By means of a leverage the
      needle follows the abdominal respiratory motion. The needle is visible as a
      blurred spot in every CT slice. The method was tested with nine patients. A
      series of volume scans during free breathing was performed. The detected
      positions of the moving needle in every single slice were compared to each other
      thus enabling respiratory state assignment. The tool is an inexpensive
      alternative to complex respiratory measuring tools for four dimensional (4D) CT
      and was greatly accepted in the clinic due to its simplicity.

PMID- 17022207
TI  - Accuracy of patient dose calculation for lung IMRT: A comparison of Monte Carlo,
      convolution/superposition, and pencil beam computations.
AB  - The accuracy of dose computation within the lungs depends strongly on the
      performance of the calculation algorithm in regions of electronic disequilibrium
      that arise near tissue inhomogeneities with large density variations. There is a
      lack of data evaluating the performance of highly developed analytical dose
      calculation algorithms compared to Monte Carlo computations in a clinical
      setting. We compared full Monte Carlo calculations (performed by our Monte Carlo
      dose engine MCDE) with two different commercial convolution/superposition (CS)
      implementations (Pinnacle-CS and Helax-TMS's collapsed cone model Helax-CC) and
      one pencil beam algorithm (Helax-TMS's pencil beam model Helax-PB) for 10
      intensity modulated radiation therapy (IMRT) lung cancer patients. Treatment
      plans were created for two photon beam qualities (6 and 18 MV). For each dose
      calculation algorithm, patient, and beam quality, the following set of clinically
      relevant dose-volume values was reported: (i) minimal, median, and maximal dose
      (Dmin, D50, and Dmax) for the gross tumor and planning target volumes (GTV and
      PTV); (ii) the volume of the lungs (excluding the GTV) receiving at least 20 and
      30 Gy (V20 and V30) and the mean lung dose; (iii) the 33rd percentile dose (D33)
      and Dmax delivered to the heart and the expanded esophagus; and (iv) Dmax for the
      expanded spinal cord. Statistical analysis was performed by means of one-way
      analysis of variance for repeated measurements and Tukey pairwise comparison of
      means. Pinnacle-CS showed an excellent agreement with MCDE within the target
      structures, whereas the best correspondence for the organs at risk (OARs) was
      found between Helax-CC and MCDE. Results from Helax-PB were unsatisfying for both
      targets and OARs. Additionally, individual patient results were analyzed. Within
      the target structures, deviations above 5% were found in one patient for the
      comparison of MCDE and Helax-CC, while all differences between MCDE and Pinnacle
      CS were below 5%. For both Pinnacle-CS and Helax-CC, deviations from MCDE above
      5% were found within the OARs: within the lungs for two (6 MV) and six (18 MV)
      patients for Pinnacle-CS, and within other OARs for two patients for Helax-CC
      (for Dmax of the heart and D33 of the expanded esophagus) but only for 6 MV. For
      one patient, all four algorithms were used to recompute the dose after replacing
      all computed tomography voxels within the patient's skin contour by water. This
      made all differences above 5% between MCDE and the other dose calculation
      algorithms disappear. Thus, the observed deviations mainly arose from differences
      in particle transport modeling within the lungs, and the commissioning of the
      algorithms was adequately performed (or the commissioning was less important for
      this type of treatment). In conclusion, not one pair of the dose calculation
      algorithms we investigated could provide results that were consistent within 5%
      for all 10 patients for the set of clinically relevant dose-volume indices
      studied. As the results from both CS algorithms differed significantly, care
      should be taken when evaluating treatment plans as the choice of dose calculation
      algorithm may influence clinical results. Full Monte Carlo provides a great
      benchmarking tool for evaluating the performance of other algorithms for patient
      dose computations.

PMID- 17022208
TI  - Resolution at oblique incidence angles of a flat panel imager for breast
      tomosynthesis.
AB  - Oblique incidence of x rays on an imaging detector causes blurring that reduces
      spatial resolution. For simple projection imaging this effect is small and often
      ignored. However, for breast tomosynthesis, the incidence angle can be larger
      (>20 degrees), leading to increased blur for some of the projections. The
      modulation transfer function (MTF) is measured for a typical phosphor-coupled
      flat-panel detector versus angular incidence of the x-ray beam for two x-ray
      spectra: 26 kV Mo/Mo and 40 kV Rh/Al. At an incidence angle of 40 degrees the MTF
      at 5 mm(-1) falls by 35% and 40% for each spectrum, respectively (and 65%/80% at
      8 mm(-1)). Increasing the detector absorber thickness to achieve improved quantum
      efficiency will cause the blurring effect due to beam obliquity to become
      greater. The impact of this blur is likely to cause misregistration and increased
      relative noise in tomosynthesis reconstructed images.

PMID- 17022209
TI  - Dosimetric characteristics of a newly designed grid block for megavoltage photon
      radiation and its therapeutic advantage using a linear quadratic model.
AB  - Grid radiation therapy with megavoltage x-ray beam has been proven to be an
      effective technique for management of large, bulky malignant tumors. The clinical
      advantage of GRID therapy, combined with conventional radiation therapy, has been
      demonstrated using a prototype GRID block [Mohiuddin, Curtis, Grizos, and
      Komarnicky, Cancer 66, 114-118 (1990)]. Recently, a new GRID block design with
      improved dosimetric properties has become commercially available from Radiation
      Product Design, Inc. (Albertive, MN). This GRID collimator consists of an array
      of focused apertures in a cerrobend block arranged in a hexagonal pattern having
      a circular cross-section with a diameter and center-to-center spacing of 14.3 and
      21.1 mm, respectively, in the plane of isocenter. In this project, dosimetric
      characteristics of the newly redesigned GRID block have been investigated for a
      Varian 21EX linear accelerator (Varian Associates, Palo Alto, CA). These
      determinations were performed using radiographic films, thermoluminescent
      dosimeters in Solid Water phantom materials, and an ionization chamber in water.
      The output factor, percentage depth dose, beam profiles, and isodose
      distributions of the GRID radiation as a function of field size and beam energy
      have been measured using both 6 and 18 MV x-ray beams. In addition, the
      therapeutic advantage obtained from this treatment modality with the new GRID
      block design for a high, single fraction of dose has been calculated using the
      linear quadratic model with alpha/beta ratios for typical tumor and normal cells.
      These biological characteristics of the new GRID block design will also be
      presented.

PMID- 17022210
TI  - Evaluation of two methods of predicting MLC leaf positions using EPID
      measurements.
AB  - In intensity modulated radiation treatments (IMRT), the position of the field
      edges and the modulation within the beam are often achieved with a multileaf
      collimator (MLC). During the MLC calibration process, due to the finite accuracy
      of leaf position measurements, a systematic error may be introduced to leaf
      positions. Thereafter leaf positions of the MLC depend on the systematic error
      introduced on each leaf during MLC calibration and on the accuracy of the leaf
      position control system (random errors). This study presents and evaluates two
      methods to predict the systematic errors on the leaf positions introduced during
      the MLC calibration. The two presented methods are based on a series of
      electronic portal imaging device (EPID) measurements. A comparison with film
      measurements showed that the EPID could be used to measure leaf positions without
      introducing any bias. The first method, referred to as the "central leaf method,"
      is based on the method currently used at this center for MLC leaf calibration. It
      mimics the manner in which leaf calibration parameters are specified in the MLC
      control system and consequently is also used by other centers. The second method,
      a new method proposed by the authors and referred to as the "individual leaf
      method," involves the measurement of two positions for each leaf (-5 and +15 cm)
      and the interpolation and extrapolation from these two points to any other given
      position. The central leaf method and the individual leaf method predicted leaf
      positions at prescribed positions of -11, 0, 5, and 10 cm within 2.3 and 1.0 mm,
      respectively, with a standard deviation (SD) of 0.3 and 0.2 mm, respectively. The
      individual leaf method provided a better prediction of the leaf positions than
      the central leaf method. Reproducibility tests for leaf positions of -5 and +15
      cm were performed. The reproducibility was within 0.4 mm on the same day and 0.4
      mm six weeks later (1 SD). Measurements at gantry angles of 0 degrees, 90
      degrees, and 270 degrees for leaf positions of -5 and +15 cm showed no
      significant effect of gravity. The individual leaf method could be used in
      various applications to improve the accuracy of radiotherapy treatment from
      planning to delivery. Three cases are discussed: IMRT beam verification, MLC
      calibration and dose calculation.

PMID- 17022211
TI  - X-ray imaging with amorphous selenium: pulse height measurements of avalanche
      gain fluctuations.
AB  - Avalanche multiplication in amorphous selenium (a-Se) can provide a large,
      adjustable gain for active matrix flat panel imagers (AMFPI), enabling quantum
      noise limited x-ray imaging during both radiography and fluoroscopy. In the case
      of direct conversion AMFPI, the multiplication factor for each x ray is a
      function of its depth of interaction, and the resulting variations in gain can
      reduce the detective quantum efficiency (DQE) of the system. An experimental
      method was developed to measure gain fluctuations by analyzing images of
      individual x rays that were obtained using a video camera with an a-Se target
      operated in avalanche mode. Pulse height spectra (PHS) of the charge produced per
      x ray were recorded for monoenergetic 30.9, 49.4, and 73.8 keV x-ray sources. The
      rapid initial decay and long tail of each PHS can be explained by a model in
      which positive charge dominates the initiation of avalanche. The Swank
      information factor quantifies the effect of gain fluctuation on DQE and was
      calculated from the PHS. The information factor was found to be 0.5 for a 25
      microm a-Se layer with a maximum gain of approximately 300. Changing the energy
      of the incident x ray influenced the range of the primary photoelectron and
      noticeably affected the tail of the experimental PHS, but did not significantly
      change the avalanche Swank factor.

PMID- 17022212
TI  - Three-dimensional imaging of xenograft tumors using optical computed and emission
      tomography.
AB  - The physical basis and preliminary applications of optical computed tomography
      (optical-CT) and optical emission computed tomography (optical-ECT) are
      introduced, as new techniques with potential to provide unique 3D information on
      a variety of aspects of tumor structure and function. A particular focus here is
      imaging tumor micro-vasculature, and the spatial distribution of viable tumor
      cells, although the techniques have the potential for much wider application. The
      principle attractiveness of optical-CT and optical-ECT are that high resolution
      (<20 microm) and high contrast co-registered 3D images of structure and function
      can be acquired for relatively large intact samples. The unique combination of
      high contrast and resolution offers advantages over micro-CT and micro-MRI, and
      the lack of requirement for sectioning offers advantages over confocal
      microscopy, conventional microscopy, and histological sectioning techniques.
      Optical-CT/ECT are implemented using in-house custom apparatus and a commercial
      dissecting microscope capable of both transmission and fluorescence imaging.
      Basic studies to characterize imaging performance are presented. Negligible
      geometrical distortion and accurate reconstruction of relative attenuation
      coefficients was observed. Optical-CT and optical-ECT are investigated here by
      application to high resolution imaging of HCT116 xenograft tumors, about 1 cc in
      dimension, which were transfected with constitutive red fluorescent protein
      (RFP). Tumor microvasculature was stained in vivo by tail vein injection of
      either passive absorbing dyes or active fluorescent markers (FITC conjugated
      lectin). Prior to imaging, the tumors were removed (ex vivo) and optically
      cleared in a key process to make the samples amenable to light transmission. The
      cleared tumors were imaged in three modes (i) optical-CT to image the 3D
      distribution of microvasculature as indicated by absorbing dye, (ii) optical-ECT
      using the FITC excitation and emission filter set, to determine microvasculature
      as indicated by lectin-endothelial binding, and (iii) optical-ECT using the
      DSRed2 filter set to determine the 3D distribution of viable tumor as indicated
      by RFP emission. A clear correlation was observed between the independent
      vasculature imaging modes (i) and (ii) and postimaging histological sections,
      providing substantial validation of the optical-CT and optical-ECT techniques.
      Strong correlation was also observed between the RFP imaging of mode iii, and
      modes i and ii, supporting the intuitive conclusion that well-perfused regions
      contain significant viable tumor. In summary, optical-CT and optical-ECT, when
      combined with new optical clearing techniques, represent powerful new imaging
      modalities with potential for providing unique information on the structure and
      function of tumors.

PMID- 17022213
TI  - Finding corresponding regions of interest in mediolateral oblique and
      craniocaudal mammographic views.
AB  - In this paper we present a method to link potentially suspicious mass regions
      detected by a Computer-Aided Detection (CAD) scheme in mediolateral oblique (MLO)
      and craniocaudal (CC) mammographic views of the breast. For all possible
      combinations of mass candidate regions, a number of features are determined.
      These features include the difference in the radial distance from the candidate
      regions to the nipple, the gray scale correlation between both regions, and the
      mass likelihood of the regions determined by the single view CAD scheme. Linear
      Discriminant Analysis (LDA) is used to discriminate between correct and incorrect
      links. The method was tested on a set of 412 cancer cases. In each case a
      malignant mass, architectural distortion, or asymmetry was annotated. In 92% of
      these cases the candidate mass detections by CAD included the cancer regions in
      both views. It was found that in 82% of the cases a correct link between the true
      positive regions in both views could be established by our method. Possible
      applications of the method may be found in multiple view analysis to improve CAD
      results, and for the presentation of CAD results to the radiologist on a
      mammography workstation.

PMID- 17022214
TI  - A comparison of techniques for simulating set-up error and uncertainty in head
      and neck IMRT.
AB  - We have compared four computational methods for quantifying the effect of set-up
      error and uncertainty on delivered doses to targets and organs at risk in the
      intensity modulated radiation therapy treatment of head and neck cancer. These
      four methods were direct simulation, simple convolution, plus two modified
      convolution approaches. Discrepancies of up to 20% in the equivalent uniform dose
      (EUD) between direct simulation and simple convolution were estimated for the
      relatively superficial parotid gland at a systematic set-up error of 6 mm
      standard deviation and a random uncertainty of 2 mm standard deviation. Truncated
      convolution agreed with direct simulation to within 6% for all situations
      studied. However, of the four methods, only direct simulation can quantify the
      range of outcomes (EUD) associated with a finite number of courses and fractions.
      Our results are particularly relevant to the design of dose escalation studies in
      head and neck cancer.

PMID- 17022215
TI  - The importance of applicator design for intraluminal brachytherapy of rectal
      cancer.
AB  - An important aspect of designing an applicator for radiation treatment of rectal
      cancer is the ability to minimize dose to the mucosa and noninvolved parts of the
      rectum wall. For this reason we investigated a construction of a flexible
      multichannel applicator with several channels placed along the periphery of a
      cylinder and a construction of a rigid cylinder with a central channel and
      interchangeable shields. Calculations of the dose gradient, dose homogeneity in
      the tumor, and shielding ability were performed for the two applicators in
      question. Furthermore, the influence on dose distribution around a flexible
      multichannel applicator from an unintended off-axis positioning of the source
      inside a bent channel was investigated by film measurements on a single bent
      catheter. Calculations showed that a single-channel applicator with
      interchangeable shields yields a higher degree of shielding and has a better dose
      homogeneity in the tumor volume than that of a multi-channel applicator. A single
      channel applicator with interchangeable shields was manufactured, and the
      influence of different size of shield angle on dose rate in front of and behind
      the shields was measured. While dose rate in front of the shield and shielding
      ability are closely independent of the size of the shield angle when measured 1
      cm from the applicator surface, dose rate in more distant volumes will to some
      extent be influenced by shield angle due to volume scatter conditions.

PMID- 17022216
TI  - Experimental determination of the radial dose function of 90Sr/90Y IVBT sources.
AB  - A series of measurements were undertaken using both high sensitivity radiochromic
      film and new lithium fluoride thermoluminescent dosimeters in a liquid water
      medium to define the radial dose function of 90Sr/90Y beta emitting intravascular
      brachytherapy sources more accurately. These measurements of a single 5 French
      source pellet served to verify current Monte Carlo transport models and
      extrapolation chamber measurements of the radial dose function, thus providing
      the recommended independent published measurements for g(r) of these sources. A
      slight deviation in the published radial dose function at depth leads the authors
      to recommend that treatment planning be performed using updated g(r) values from
      current Monte Carlo transport models verified by measurements such as those shown
      in this investigation.

PMID- 17022217
TI  - A realistic phantom for brain-shift simulations.
AB  - Validation of techniques that characterize and correct for brain shift for image
      guided surgery requires a realistic anthropomorphic phantom for use as a gold
      standard. The purpose of this study was to determine the characteristics of a
      deformable brain phantom made of polyvinyl alcohol cryogel (PVAc). The phantom
      was made of three layers of PVAc with inserted plastic tubes to simulate blood
      vessels. A catheter with an inflatable balloon was placed under the phantom in
      order to deform it in a nonlinear manner. The reproducibility of the elastic
      deformation was evaluated using MR imaging and surface measurements. Our
      experiments show that the phantom is well suited for MR and ultrasound imaging (B
      mode and Doppler) with sub-millimeter reproducibility for the deformations.

PMID- 17022218
TI  - Basic nonlinear acoustics: an introduction for radiological physicists.
AB  - Presented is a brief introduction to nonlinear acoustics, a topic of increasing
      importance in modern diagnostic ultrasound. Specifically treated is shock wave
      and harmonic production in lossless media. We also present a description of
      linear attenuation mechanisms in soft tissue and finally nonlinear propagation in
      soft tissue.

PMID- 17022219
TI  - Determination of dosimetrical quantities used in microbeam radiation therapy
      (MRT) with Monte Carlo simulations.
AB  - Microbeam radiation therapy (MRT) is being performed by using an array of narrow
      rectangular x-ray beams (typical beam sizes 25 microm X 1 cm), positioned close
      to each other (typically 200 microm separation), to irradiate a target tissue.
      The ratio of peak-to-valley doses (PVDR's) in the composite dose distribution has
      been found to be strongly correlated with the normal tissue tolerance and the
      therapeutic effect of MRT. In this work a Monte Carlo (MC) study of the depth-
      and lateral-dose profiles in water for single x-ray microbeams of different
      shapes and energies has been performed with the MC code PENELOPE. The
      contributions to the dose deposition from different interaction types have been
      determined at different distances from the center of the microbeam. The
      dependence of the peak dose, in a water phantom, on the microbeam field size used
      in the preclinical trials, has been demonstrated. Composite dose distributions
      for an array of microbeams were obtained using superposition algorithms and
      PVDR's were determined and compared with literature results obtained with other
      Monte Carlo codes. The dependence of the PVDR's on microbeam width, x-ray energy
      used, and on the separation between adjacent microbeams has been studied in
      detail.

PMID- 17022220
TI  - Dosimetric characterization of radionuclides for systemic tumor therapy:
      influence of particle range, photon emission, and subcellular distribution.
AB  - Various radionuclides have been proposed for systemic tumor therapy. However, in
      most dosimetric analysis of proposed radionuclides the charged particles are
      taken into consideration while the potential photons are ignored. The photons
      will cause undesirable irradiation of normal tissue, and increase the probability
      of toxicity in, e.g., the bone marrow. The aim of this study was to investigate
      the dosimetric properties according to particle range, photon emission, and
      subcellular radionuclide distribution, of a selection of radionuclides used or
      proposed for radionuclide therapy, and to investigate the possibility of dividing
      radionuclides into groups according to their dosimetric properties. The absorbed
      dose rate to the tumors divided by the absorbed dose rate to the normal tissue
      (TND) was estimated for different tumor sizes in a mathematical model of the
      human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres
      of different sizes (1 ng-100 g). The radionuclides were either assumed to be
      uniformly distributed throughout the entire tumor and normal tissue, or located
      in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of
      the normal cells. Fifty-nine radionuclides were studied together with
      monoenergetic electrons, positrons, and alpha particles. The tumor and normal
      tissue were assumed to be of water density. The activity concentration ratio
      between the tumor and normal tissue was assumed to be 25. The radionuclides
      emitting low-energy electrons combined with a low photon contribution, and the
      alpha emitters showed high TND values for most tumor sizes. Electrons with higher
      energy gave reduced TND values for small tumors, while a higher photon
      contribution reduced the TND values for large tumors. Radionuclides with high
      photon contributions showed low TND value for all tumor sizes studied. The
      radionuclides studied could be divided into four main groups according to their
      TND values: beta emitters, Auger electron emitters, photon emitters, and alpha
      emitters. The TND values of the beta emitters were not affected by the
      subcellular distribution of the radionuclide. The TND values of the Auger
      electron emitters were affected by the subcellular radionuclide distribution. The
      photon emitters showed low TND values that were only slightly affected by the
      subcellular radionuclide distribution. The alpha emitters showed high TND values
      that were only slightly affected by the subcellular radionuclide distribution.
      This dosimetric characterization of radionuclides may be valuable in choosing the
      appropriate radionuclides for specific therapeutic applications.

PMID- 17022221
TI  - Monte Carlo study of backscatter in a flattening filter free clinical
      accelerator.
AB  - In conventional linear accelerators, the flattening filter provides a uniform
      lateral dose profile. In intensity modulated radiation therapy applications,
      however, the flatness of the photon field and hence the presence of a flattening
      filter, is not necessary. Removing the filter may provide some advantages, such
      as faster treatments and smaller out-of-field doses to the patients. In clinical
      accelerators the backscattered radiation dose from the collimators must be taken
      into account when the dose to the target volume in the patient is being
      determined. In the case of a conventional machine, this backscatter is known to
      great precision. In a flattening filter free accelerator, however, the amount of
      backscatter may be different. In this study we determined the backscatter
      contribution to the monitor chamber signal in a flattening filter free clinical
      accelerator (Varian Clinac 21EX) with Monte Carlo simulations. We found that with
      the exception of very small fields in the 18-MV photon mode, the contribution of
      backscattered radiation to the monitor signal did not differ from that of
      conventional machines with a flattening filter. Hence, a flattening filter free
      clinical accelerator would not necessitate a different backscatter correction.

PMID- 17022222
TI  - Tomographic physical phantom of the newborn child with real-time dosimetry I.
      Methods and techniques for construction.
AB  - A tomographic phantom representing a newborn female patient was constructed using
      tissue-equivalent materials previously developed at the University of Florida.
      This phantom was constructed using contoured images from an actual patient data
      set, a whole-body computed tomography of a newborn cadaver previously described
      by Nipper et al. [Phys. Med. Biol. 47, 3143-1364 (2002)]. Four types of material
      are incorporated in the phantom: soft tissue, bone tissue, lung tissue, and air.
      The phantom was constructed on a slice-by-slice basis with a z-axis resolution of
      5 mm, channels for dosimeters (thermoluminescent dosimeter (TLD), metal-oxide
      semiconductor field-effect transistor, or gated fiber-optic-coupled dosimeter
      (GFOC)) were machined into slices prior to assembly, and the slices were then
      fixed together to form the complete phantom. The phantom will be used in
      conjunction with an incorporated dosimetry system to calculate individual organ
      and effective doses delivered to newborn patients during various diagnostic
      procedures, including, but not limited to, projection radiography and computed
      tomography. Included in this paper are images detailing the construction process,
      and images of the completed phantom.

PMID- 17022223
TI  - A tomographic physical phantom of the newborn child with real-time dosimetry. II.
      Scaling factors for calculation of mean organ dose in pediatric radiography.
AB  - Following the recent completion of a tomographic physical newborn dosimetry
      phantom with incorporated metal-oxide-semiconductor field effect transistor
      (MOSFET) dosimetry system, it was necessary to derive scaling factors in order to
      calculate organ doses in the physical phantom given point dose measurements via
      the MOSFET dosimeters (preceding article in this issue). In this study, we
      present the initial development of scaling factors using projection radiograph
      data. These point-to-organ dose scaling factors (SF(POD)) were calculated using a
      computational phantom created from the same data set as the physical phantom, but
      which also includes numerous segmented internal organs and tissues. The creation
      of these scaling factors is discussed, as well as the errors associated when
      using only point dose measurements to calculate mean organ doses and effective
      doses in physical phantoms. Scaling factors for various organs ranged from as low
      as 0.70 to as high as 1.71. Also, the ability to incorporate improvements in the
      computational phantom into the physical phantom using scaling factors is
      discussed. An comprehensive set of SF(POD) values is presented in this article
      for application in pediatric radiography of newborn patients.

PMID- 17022224
TI  - Properties of preprocessed sinogram data in x-ray computed tomography.
AB  - The accurate determination of x-ray signal properties is important to several
      computed tomography (CT) research and development areas, notably for statistical
      reconstruction algorithms and dose-reduction simulation. The most commonly used
      model of CT signal formation, assuming monoenergetic x-ray sources with quantum
      counting detectors obeying simple Poisson statistics, does not reflect the actual
      physics of CT acquisition. This paper describes a more accurate model, taking
      into account the energy-integrating detection process, nonuniform flux profiles,
      and data-conditioning processes. Methods are developed to experimentally measure
      and theoretically calculate statistical distributions, as well as techniques to
      analyze CT signal properties. Results indicate the limitations of current models
      and suggest improvements for the description of CT signal properties.

PMID- 17022225
TI  - A deformable image registration method to handle distended rectums in prostate
      cancer radiotherapy.
AB  - In image-guided adaptive radiotherapy, it is important to have the capability to
      automatically and accurately delineate the rectal wall, which is a major dose
      limiting organ in prostate cancer radiotherapy. As image registration is a
      process to find the spatial correspondence between two images, a major challenge
      in intensity-based deformable image registration is to deal with the situation
      where no correspondence exists for some objects between the two images to be
      registered. One example is the variation of rectal contents due to the presence
      and absence of bowel gas. The intensity-based deformable image registration
      methods alone cannot create the correct spatial transformation if there is no
      correspondence between the source and target images. In this study we implemented
      an automatic image intensity modification procedure to create artificial gas
      pockets in the planning computed tomography (CT) images. A diffusion-based
      deformable image registration algorithm was developed to use an adaptive
      smoothing algorithm to better handle large organ deformations. The process was
      tested in 15 prostate cancer cases and 30 daily CT images containing the largest
      distended rectums. The manually delineated rectums agreed well with the
      autodelineated rectums when using the image-intensity modification procedure.

PMID- 17022226
TI  - Compact multileaf collimator for conformal and intensity modulated fast neutron
      therapy: electromechanical design and validation.
AB  - The electromechanical properties of a 120-leaf, high-resolution, computer
      controlled, fast neutron multileaf collimator (MLC) are presented. The MLC
      replaces an aging, manually operated multirod collimator. The MLC leaves project
      5 mm in the isocentric plane perpendicular to the beam axis. A taper is included
      on the leaves matching beam divergence along one axis. The 5-mm leaf projection
      width is chosen to give high-resolution conformality across the entire field. The
      maximum field size provided is 30 x 30 cm2. To reduce the interleaf transmission
      a 0.254-mm blocking step is included. End-leaf steps totaling 0.762 mm are also
      provided allowing opposing leaves to close off within the primary radiation beam.
      The neutron MLC also includes individual 45 degrees and 60 degrees automated
      universal tungsten wedges. The automated high-resolution neutron collimation
      provides an increase in patient throughput capacity, enables a new modality,
      intensity modulated neutron therapy, and limits occupational radiation exposure
      by providing remote operation from a shielded console area.

PMID- 17022227
TI  - A computer simulated phantom study of tomotherapy dose optimization based on
      probability density functions (PDF) and potential errors caused by low
      reproducibility of PDF.
AB  - Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can
      be converted to a probability density function (PDF), which describes the
      probability of the tumor at a certain position, for PDF based treatment planning.
      Using this method in simulated sequential tomotherapy, we study the dose
      reduction of normal tissues and more important, the effect of PDF reproducibility
      on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained
      from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The
      first PDF was accumulated from a 300 s scan and the second PDF was calculated
      from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam
      fluences based on the second PDF were delivered to the hypothetical gross target
      volume (GTV) of a lung phantom that moved following the first PDF The
      reproducibility between two PDFs varied from low (78%) to high (94.8%) when the
      second scan time increased from 5 s to 300 s. When a highly reproducible PDF was
      used in optimization, the dose coverage of GTV was maintained; phantom lung
      receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom
      lung dose was reduced by 9.6%. However, optimization based on PDF with low
      reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased
      nearly exponentially as the PDF error increased. Therefore, although the dose of
      the tumor surrounding tissue can be theoretically reduced by PDF based treatment
      planning, the reliability and applicability of this method highly depend on if a
      reproducible PDF exists and is measurable. By correlating the dosimetric error
      and PDF error together, a useful guideline for PDF data acquisition and patient
      qualification for PDF based planning can be derived.

PMID- 17022228
TI  - A time of opportunity in the education of medical physicists: Report of a multi
      organizational summit on the education of medical physicists.

PMID- 17022229
TI  - Investigation of tilted dose kernels for portal dose prediction in a-Si
      electronic portal imagers.
AB  - The effect of beam divergence on dose calculation via Monte Carlo generated dose
      kernels was investigated in an amorphous silicon electronic portal imaging device
      (EPID). The flat-panel detector was simulated in EGSnrc with an additional 3.0 cm
      water buildup. The model included details of the detector's imaging cassette and
      the front cover upstream of it. To approximate the effect of the EPID's rear
      housing, a 2.1 cm air gap and 1.0 cm water slab were introduced into the
      simulation as equivalent backscatter material. Dose kernels were generated with
      an incident pencil beam of monoenergetic photons of energy 0.1, 2, 6, and 18 MeV.
      The orientation of the incident pencil beam was varied from 0 degrees to 14
      degrees in 2 degrees increments. Dose was scored in the phosphor layer of the
      detector in both cylindrical (at 0 degrees) and Cartesian (at 0 degrees - 14
      micro) geometries. To reduce statistical fluctuations in the Cartesian geometry
      simulations at large radial distances from the incident pencil beam, the voxels
      were first averaged bilaterally about the pencil beam and then combined into
      concentric square rings of voxels. Profiles of the EPID dose kernels displayed
      increasing asymmetry with increasing angle and energy. A comparison of the
      superposition (tilted kernels) and convolution (parallel kernels) dose
      calculation methods via the chi-comparison test (a derivative of the gamma
      evaluation) in worst-case-scenario geometries demonstrated an agreement between
      the two methods within 0.0784 cm (one pixel width) distance-to-agreement and up
      to a 1.8% dose difference. More clinically typical field sizes and source-to
      detector distances were also tested, yielding at most a 1.0% dose difference and
      the same distance-to-agreement. Therefore, the assumption of parallel dose
      kernels has less than a 1.8% dosimetric effect in extreme cases and less than a
      1.0% dosimetric effect in most clinically relevant situations and should be
      suitable for most clinical dosimetric applications. The resulting time difference
      for the parallel kernel assumption versus the tilted kernels was 10.5 s vs 18 h
      (a factor of approximately 6000), dependent on existing hardware and software
      details.

PMID- 17022230
TI  - On the accuracy of techniques for obtaining the calibration coefficient N(K) of
      192Ir HDR brachytherapy sources.
AB  - The accuracy of interpolation or averaging procedures for obtaining the
      calibration coefficient N(K) for 192Ir high-dose-rate brachytherapy sources has
      been investigated using the EGSnrc Monte Carlo simulation system. It is shown
      that the widely used two-point averaging procedure of Goetsch et al. [Med. Phys.
      18, 462 (1991)] has some conceptual problems. Most importantly, they recommended,
      as did the IAEA, averaging A(wall)N(K) values whereas one should average 1/N(K)
      values. In practice this and other issues are shown to have little effect except
      for Goetsch et al.'s methods for determining A(wall) values. Their method of
      generalizing the A(wall) values measured in one geometry to other geometries is
      incorrect by up to 2%. However, these errors in A(wall) values cause systematic
      errors of only 0.3% in 192Ir calibration coefficients. It is shown that A(wall)
      values need not be included in the averaging technique at all, thereby
      simplifying the technique considerably. It is demonstrated that as long as ion
      chambers with a flat response are used and/or very heavily filtered 250 kV (or
      higher) beams of x rays are used in the averaging, then almost all techniques can
      provide adequate accuracy.

PMID- 17022231
TI  - A continuous 4D motion model from multiple respiratory cycles for use in lung
      radiotherapy.
AB  - Respiratory motion causes errors when planning and delivering radiotherapy
      treatment to lung cancer patients. To reduce these errors, methods of acquiring
      and using four-dimensional computed tomography (4DCT) datasets have been
      developed. We have developed a novel method of constructing computational motion
      models from 4DCT. The motion models attempt to describe an average respiratory
      cycle, which reduces the effects of variation between different cycles. They
      require substantially less memory than a 4DCT dataset, are continuous in space
      and time, and facilitate automatic target propagation and combining of doses over
      the respiratory cycle. The motion models are constructed from CT data acquired in
      cine mode while the patient is free breathing (free breathing CT - FBCT). A
      "slab" of data is acquired at each couch position, with 3-4 contiguous slabs
      being acquired per patient. For each slab a sequence of 20 or 30 volumes was
      acquired over 20 seconds. A respiratory signal is simultaneously recorded in
      order to calculate the position in the respiratory cycle for each FBCT.
      Additionally, a high quality reference CT volume is acquired at breath hold. The
      reference volume is nonrigidly registered to each of the FBCT volumes. A motion
      model is then constructed for each slab by temporally fitting the nonrigid
      registration results. The value of each of the registration parameters is related
      to the position in the respiratory cycle by fitting an approximating B spline to
      the registration results. As an approximating function is used, and the data is
      acquired over several respiratory cycles, the function should model an average
      respiratory cycle. This can then be used to calculate the value of each degree of
      freedom at any desired position in the respiratory cycle. The resulting nonrigid
      transformation will deform the reference volume to predict the contents of the
      slab at the desired position in the respiratory cycle. The slab model predictions
      are then concatenated to produce a combined prediction over the entire region of
      interest. We have performed a number of experiments to assess the accuracy of the
      nonrigid registration results and the motion model predictions. The individual
      slab models were evaluated by expert visual assessment and the tracking of easily
      identifiable anatomical points. The combined models were evaluated by calculating
      the discontinuities between the transformations at the slab boundaries. The
      experiments were performed on five patients with a total of 18 slabs between
      them. For the point tracking experiments, the mean distance between where a
      clinician manually identified a point and where the registration results located
      the point, the target registration error (TRE), was 1.3 mm. The mean distance
      between a manually identified point and the models prediction of the point's
      location, the target model error (TME), was 1.6 mm. The mean discontinuity
      between model predictions at the slab boundaries, the Continuity Error, was 2.2
      mm. The results show that the motion models perform with a level of accuracy
      comparable to the slice thickness of 1.5 mm.

PMID- 17022232
TI  - Magnitude and effects of x-ray scatter in a 256-slice CT scanner.
AB  - We developed a prototype 256-slice CT scanner that employs continuous rotation of
      a cone-beam with a larger cone angle than conventional multidetector CTs (MDCT)
      to ensure a wide field of view. However, a larger cone angle may result in image
      deterioration due to increased x-ray scatter. Scattered radiation causes the
      detected signals to deviate from the true measurement of primary x-ray intensity
      and may result in artifacts (e.g., cupping and streak artifacts), quantitative
      inaccuracy in reconstructed CT number, and degradation of contrast-to-noise ratio
      (CNR). To reduce the effects of scatter, the 256-slice scanner incorporates an
      antiscatter collimator. Here, we estimated the magnitude of x-ray scatter in the
      prototype 256-slice CT scanner under clinical scan conditions and quantified the
      effects of this scatter on CT number accuracy, image noise, uniformity, and low
      contrast detectability. Although most experiments were performed with the
      antiscatter collimator, we also estimated the magnitude of x-ray scatter without
      the collimator to evaluate the scatter rejection efficiency of the collimator.
      The scatter-to-primary energy fluence ratio (SPR) without the collimator
      increased as cone angle increased, with estimated values of 49.7% for a 138 mm
      beam width with a phantom of 200 mm diameter, and 78.5% for a 320 mm diameter
      phantom. Estimated SPR was drastically decreased with the collimator, with an SPR
      reduction rate (ratio of SPR with and without the collimator) of 12.7% and 16.8%
      for the 200 and 320 mm diameter phantoms, respectively. The reduction in x-ray
      scatter by the collimator resulted in a considerable reduction in scatter
      effects. The measured uniformity was good and was independent of scatter amount.
      Although scatter still affected CT number accuracy, this could be corrected by
      rescaling. Further, although the CNR was decreased, in theory at least, the
      change was so subtle that it had no substantial effect on low-contrast
      detectability.

PMID- 17022233
TI  - Three-dimensional portal image-based dose reconstruction in a virtual phantom for
      rapid evaluation of IMRT plans.
AB  - A new method for rapid evaluation of intensity modulated radiation therapy (IMRT)
      plans has been developed, using portal images for reconstruction of the dose
      delivered to a virtual three-dimensional (3D) phantom. This technique can replace
      an array of less complete but more time-consuming measurements. A reference dose
      calculation is first created by transferring an IMRT plan to a cylindrical
      phantom, retaining the treatment gantry angles. The isocenter of the fields is
      placed on or near the phantom axis. This geometry preserves the relative
      locations of high and low dose regions and has the required symmetry for the dose
      reconstruction. An electronic portal image (EPI) is acquired for each field,
      representing the dose in the midplane of a virtual phantom. The image is
      convolved with a kernel to correct for the lack of scatter, replicating the
      effect of the cylindrical phantom surrounding the dose plane. This avoids the
      need to calculate fluence. Images are calibrated to a reference field that
      delivers a known dose to the isocenter of this phantom. The 3D dose matrix is
      reconstructed by attenuation and divergence corrections and summed to create a
      dose matrix (PI-dose) on the same grid spacing as the reference calculation.
      Comparison of the two distributions is performed with a gradient-weighted 3D dose
      difference based on dose and position tolerances. Because of its inherent
      simplicity, the technique is optimally suited for detecting clinically
      significant variances from a planned dose distribution, rather than for use in
      the validation of IMRT algorithms. An analysis of differences between PI-dose and
      calculation, delta PI, compared to differences between conventional quality
      assurance (QA) and calculation, delta CQ, was performed retrospectively for 20
      clinical IMRT cases. PI-dose differences at the isocenter were in good agreement
      with ionization chamber differences (mean delta PI = -0.8%, standard deviation
      sigma = 1.5%, against delta CQ = 0.3%, sigma = 1.0%, respectively). PI-dose plane
      differences had significantly less variance than film plane differences (sigma =
      1.1 and 2.1%, respectively). Twenty-two further cases were evaluated using 3D EPI
      dosimetry alone. The mean difference delta over volumes with doses above 80% of
      the isocenter value was delta = -0.3%, sigma(delta) = 0.7%, and standard
      deviations of the distributions ranged from 1.0 to 2.0%. Verification time per
      plan, from initial calculation, delivery, dose reconstruction to evaluation,
      takes less than 1.5 h and is more than four times faster than conventional QA.

PMID- 17022234
TI  - Monte Carlo dose voxel kernel calculations of beta-emitting and Auger-emitting
      radionuclides for internal dosimetry: A comparison between EGSnrcMP and EGS4.
AB  - Dose-point kernels (DPKs) can be widely applied to therapeutic nuclear medicine
      to obtain more accurate absorbed dose assessments in internal dosimetry assuming
      a spherical geometry. Recently, EGSnrc-the latest in the family of EGS Monte
      Carlo codes--has been tested for isotropic monoenergetic electrons and Y-90 beta
      spectrum in spherical geometry. The availability of SPECT images allows one to
      take into account heterogeneities in activity distribution within tumors, and to
      perform dose calculations using voxel dosimetry based on Monte Carlo simulations
      in a Cartesian geometry. The purpose of this study is to evaluate the differences
      of dose distributions scored in Cartesian voxels also known as Dose Voxel Kernels
      (DVKs) for five beta-emitting (131I, 89Sr, 153Sm, 186Re, and 90Y) and Auger
      emitting (111In) radionuclides, when their computation is made using these two
      Monte Carlo codes from the same family to check if the new physics in EGSnrc
      simulation system produces DVK very different from those calculated with EGS4. We
      have calculated the DVKs for point and voxel sources in Cartesian scoring grids
      of different spatial resolutions. Our results for the point source, scored in the
      finer spatial resolution, show a poor agreement between EGSnrc and EGS4 (up to
      about 20%) for voxels closer to the origin, and a better agreement (below 5%) for
      longer distances for all radionuclides. For the voxel source, where doses were
      scored in the coarser spatial resolution, dose deposition in the central voxel is
      in good agreement for all the radionuclides; while surrounding voxels exhibit a
      slightly worse agreement.

PMID- 17022235
TI  - Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to
      account for respiratory motion.
AB  - To effectively deliver radiation dose to lung tumors, respiratory motion has to
      be considered in treatment planning. In this paper we first present a new lung
      IMRT planning algorithm, referred as the dose shaping (DS) method, that shapes
      the dose distribution according to the probability distribution of the tumor over
      the breathing cycle to account for respiratory motion. In IMRT planning a dose
      based convolution method was generally adopted to compensate for random organ
      motion by performing 4-D dose calculations using a tumor motion probability
      density function. We modified the CON-DOSE method to a dose volume histogram
      based convolution method (CON-DVH) that allows nonuniform dose distribution to
      account for respiratory motion. We implemented the two new planning algorithms on
      an in-house IMRT planning system that uses the Eclipse (Varian, Palo Alto, CA)
      planning workstation as the dose calculation engine. The new algorithms were
      compared with (1) the conventional margin extension approach in which margin is
      generated based on the extreme positions of the tumor, (2) the dose-based
      convolution method, and (3) gating with 3 mm residual motion. Dose volume
      histogram, tumor control probability, normal tissue complication probability, and
      mean lung dose were calculated and used to evaluate the relative performance of
      these approaches at the end-exhale phase of the respiratory cycle. We recruited
      six patients in our treatment planning study. The study demonstrated that the two
      new methods could significantly reduce the ipsilateral normal lung dose and
      outperformed the margin extension method and the dose-based convolution method.
      Compared with the gated approach that has the best performance in the low dose
      region, the two methods we proposed have similar potential to escalate tumor
      dose, but could be more efficient because dose is delivered continuously.

PMID- 17022236
TI  - Approximating convex pareto surfaces in multiobjective radiotherapy planning.
AB  - Radiotherapy planning involves inherent tradeoffs: the primary mission, to treat
      the tumor with a high, uniform dose, is in conflict with normal tissue sparing.
      We seek to understand these tradeoffs on a case-to-case basis, by computing for
      each patient a database of Pareto optimal plans. A treatment plan is Pareto
      optimal if there does not exist another plan which is better in every measurable
      dimension. The set of all such plans is called the Pareto optimal surface. This
      article presents an algorithm for computing well distributed points on the
      (convex) Pareto optimal surface of a multiobjective programming problem. The
      algorithm is applied to intensity-modulated radiation therapy inverse planning
      problems, and results of a prostate case and a skull base case are presented, in
      three and four dimensions, investigating tradeoffs between tumor coverage and
      critical organ sparing.

PMID- 17022237
TI  - Accuracy of treatment planning based on stereolithography in computer assisted
      surgery.
AB  - Three-dimensional stereolithographic models (SL models), made of solid acrylic
      resin derived from computed-tomography (CT) data, are an established tool for
      preoperative treatment planning in numerous fields of medicine. An innovative
      approach, combining stereolithography with computer-assisted point-to-point
      navigation, can support the precise surgical realization of a plan that has been
      defined on an SL model preoperatively. The essential prerequisites for the
      application of such an approach are: (1) The accuracy of the SL models (including
      accuracy of the CT scan and correspondence of the model with the patient's
      anatomy) and (2) the registration method used for the transfer of the plan from
      the SL model to the patient (i.e., whether the applied registration markers can
      be added to the SL model corresponding to the markers at the patient with an
      accuracy that keeps the "cumulative error" at the end of the chain of errors, in
      the order of the accuracy of contemporary navigation systems). In this study, we
      focus on these two topics: By applying image-matching techniques, we fuse the
      original CT data of the patient with the corresponding CT data of the scanned SL
      model, and measure the deviations of defined parameter (e.g., distances between
      anatomical points). To evaluate the registration method used for the planning
      transfer, we apply a point-merge algorithm, using four marker points that should
      be located at exactly corresponding positions at the patient and at connective
      bars that are added to the surface of the SL model. Again, deviations at defined
      anatomical structures are measured and analyzed statistically. Our results prove
      sufficient correspondence of the two data sets and accuracy of the registration
      method for routine clinical application. The evaluation of the SL model accuracy
      revealed an arithmetic mean of the relative deviations from 0.8% to 5.4%, with an
      overall mean deviation of 2.2%. Mean deviations of the investigated anatomical
      structures ranged from 0.8 mm to 3.2 mm. An overall mean (comprising all
      structures) of 2.5 mm was found. The fiducial registration error of the point
      merge algorithm ranged from 1.0 mm to 1.4 mm. The evaluated chain of errors
      showed a mean deviation of 2.5 mm. This study verifies that preoperative planning
      on SL models and intraoperative transfer of this plan with computer assisted
      navigation is a suitable and sufficiently reliable method for clinical
      applications.

PMID- 17022238
TI  - Dose uncertainties in photon pencil kernel calculations at off-axis positions.
AB  - The purpose of this study was to investigate the specific problems associated
      with photon dose calculations in points located at a distance from the central
      beam axis. These problems are related to laterally inhomogeneous energy fluence
      distributions and spectral variations causing a lateral shift in the beam
      quality, commonly referred to as off-axis softening (OAS). We have examined how
      the dose calculation accuracy is affected when enabling and disabling explicit
      modeling of these two effects. The calculations were performed using a pencil
      kernel dose calculation algorithm that facilitates modeling of OAS through
      laterally varying kernel properties. Together with a multi-source model that
      provides the lateral energy fluence distribution this generates the total dose
      output, i.e., the dose per monitor unit, at an arbitrary point of interest. The
      dose calculation accuracy was evaluated through comparisons with 264 measured
      output factors acquired at 5, 10, and 20 cm depth in four different megavoltage
      photon beams. The measurements were performed up to 18 cm from the central beam
      axis, inside square fields of varying size and position. The results show that
      calculations including explicit modeling of OAS were considerably more accurate,
      up to 4%, than those ignoring the lateral beam quality shift. The deviations
      caused by simplified head scatter modeling were smaller, but near the field edges
      additional errors close to 1% occurred. When enabling full physics modeling in
      the dose calculations the deviations display a mean value of -0.1%, a standard
      deviation of 0.7%, and a maximum deviation of -2.2%. Finally, the results were
      analyzed in order to quantify and model the inherent uncertainties that are
      present when leaving the central beam axis. The off-axis uncertainty component
      showed to increase with both off-axis distance and depth, reaching 1% (1 standard
      deviation) at 20 cm depth.

PMID- 17022239
TI  - New methods of MR image intensity standardization via generalized scale.
AB  - Image intensity standardization is a post-acquisition processing operation
      designed for correcting acquisition-to-acquisition signal intensity variations
      (non-standardness) inherent in Magnetic Resonance (MR) images. While existing
      standardization methods based on histogram landmarks have been shown to produce a
      significant gain in the similarity of resulting image intensities, their weakness
      is that in some instances the same histogram-based landmark may represent one
      tissue, while in other cases it may represent different tissues. This is often
      true for diseased or abnormal patient studies in which significant changes in
      image intensity characteristics may occur. In an attempt to overcome this
      problem, in this paper, we present two new intensity standardization methods
      based on two scale concepts developed in Madabhushi et al. [Computer Vision Image
      Understanding 101, 100-121 (2006)] for image processing applications. These scale
      concepts are utilized in this paper to accurately determine principal tissue
      regions within MR images. Landmarks derived from these regions are used to
      perform intensity standardization. The new methods were qualitatively and
      quantitatively evaluated on a total of 67 clinical three dimensional (3D) MR
      images corresponding to four different protocols and to normal, Multiple
      Sclerosis (MS), and brain tumor patient studies. The new scale-based methods were
      found to be better than the existing methods, with a significant improvement
      observed for severely diseased and abnormal patient studies.

PMID- 17022240
TI  - Reverse mapping of normal tissue complication probabilities onto dose volume
      histogram space: the problem of randomness of the dose volume histogram sampling.
AB  - A very important issue in contemporary inverse treatment radiotherapy planning is
      the specification of proper dose-volume constraints limiting the treatment
      planning algorithm from delivering high doses to the normal tissue surrounding
      the tumor. Recently we have proposed a method called reverse mapping of normal
      tissue complication probabilities (NTCP) onto dose-volume histogram (DVH) space,
      which allows the calculation of appropriate biologically based dose-volume
      constraints to be used in the inverse treatment planning. The method of reverse
      mapping requires random sampling from the functional space of all monotonically
      decreasing functions in the unit square. We develop, in this paper, a random
      function generator for the purpose of the reverse mapping. Since the proposed
      generator is based on the theory of random walk, it is therefore designated in
      this work, as a random walk DVH generator. It is theoretically determined that
      the distribution of the number of monotonically decreasing functions passing
      through a point in the dose volume histogram space follows the hypergeometric
      distribution. The proposed random walk DVH generator thus simulates, in a random
      fashion, trajectories of monotonically decreasing functions (finite series) that
      are situated in the unit square [0, 1] X [1,0] using the hypergeometric
      distribution. The DVH generator is an important tool in the study of reverse NTCP
      mapping for the calculation of biologically based dose-volume constraints for
      inverse treatment planning.

PMID- 17022241
TI  - A theoretical approach to the problem of dose-volume constraint estimation and
      their impact on the dose-volume histogram selection.
AB  - This paper outlines a theoretical approach to the problem of estimating and
      choosing dose-volume constraints. Following this approach, a method of choosing
      dose-volume constraints based on biological criteria is proposed. This method is
      called "reverse normal tissue complication probability (NTCP) mapping into dose
      volume space" and may be used as a general guidance to the problem of dose-volume
      constraint estimation. Dose-volume histograms (DVHs) are randomly simulated, and
      those resulting in clinically acceptable levels of complication, such as NTCP of
      5 +/- 0.5%, are selected and averaged producing a mean DVH that is proven to
      result in the same level of NTCP. The points from the averaged DVH are proposed
      to serve as physical dose-volume constraints. The population-based critical
      volume and Lyman NTCP models with parameter sets taken from literature sources
      were used for the NTCP estimation. The impact of the prescribed value of the
      maximum dose to the organ, D(max), on the averaged DVH and the dose-volume
      constraint points is investigated. Constraint points for 16 organs are
      calculated. The impact of the number of constraints to be fulfilled based on the
      likelihood that a DVH satisfying them will result in an acceptable NTCP is also
      investigated. It is theoretically proven that the radiation treatment
      optimization based on physical objective functions can sufficiently well restrict
      the dose to the organs at risk, resulting in sufficiently low NTCP values through
      the employment of several appropriate dose-volume constraints. At the same time,
      the pure physical approach to optimization is self-restrictive due to the
      preassignment of acceptable NTCP levels thus excluding possible better solutions
      to the problem.

PMID- 17022242
TI  - Experimental determination of subjective similarity for pairs of clustered
      microcalcifications on mammograms: observer study results.
AB  - Presentation of images of lesions similar to that of an unknown lesion might be
      useful to radiologists in distinguishing between benign and malignant clustered
      microcalcifications on mammograms. Investigators have been developing
      computerized schemes to select similar images from large databases. However,
      whether selected images are really similar in appearance is not examined for most
      of the schemes. In order to retrieve images that are useful to radiologists, the
      selected images must be similar from radiologists' diagnostic points of view.
      Therefore, in this study, the data of radiologists' subjective similarity for
      pairs of clustered microcalcification images were obtained from a number of
      observers, and the intra- and inter-observer variations and the intergroup
      correlations were determined to investigate whether reliable similarity ratings
      by human observers can be determined. Nineteen images of clustered
      microcalcifications, each of which was paired with six other images, were
      selected for the observer study. Thus, subjective similarity ratings for 114
      pairs of clustered microcalcifications were determined by each observer. Thirteen
      breast, ten general, and ten nonradiologists participated in the observer study;
      some of them completed the study multiple times. Although the intraobserver
      variations for the individual readings and the interobserver variations for pairs
      of observers were not small, the interobserver agreements were improved by taking
      the average of readings by the same observers. When the similarity ratings by a
      number of observers were averaged among the groups of breast, general, and
      nonradiologists, the mean differences of the ratings between the groups
      decreased, and good concordance correlations (0.846, 0.817, and 0.785) between
      the groups were obtained. The result indicates that reliable similarity ratings
      can be determined by use of this method, and the average similarity ratings by
      breast radiologists can be considered meaningful and useful for the development
      and evaluation of a computerized scheme for selection of similar images.

PMID- 17022243
TI  - Comparison of two portable solid state detectors with an improved collimation and
      alignment device for mammographic x-ray spectroscopy.
AB  - We describe a portable system for mammographic x-ray spectroscopy, based on a 2 X
      2 X 1 mm3 cadmium telluride (CdTe) solid state detector, that is greatly improved
      over a similar system based on a 3 X 3 X 2 mm3 cadmium zinc telluride (CZT) solid
      state detector evaluated in an earlier work. The CdTe system utilized new pinhole
      collimators and an alignment device that facilitated measurement of mammographic
      x-ray spectra. Mammographic x-ray spectra acquired by each system were
      comparable. Half value layer measurements obtained using an ion chamber agreed
      closely with those derived from the x-ray spectra measured by either detector.
      The faster electronics and other features of the CdTe detector allowed its use
      with a larger pinhole collimator than could be used with the CZT detector.
      Additionally, the improved pinhole collimator and alignment features of the
      apparatus permitted much more rapid setup for acquisition of x-ray spectra than
      was possible on the system described in the earlier work. These improvements in
      detector technology, collimation and ease of alignment, as well as low cost, make
      this apparatus attractive as a tool for both laboratory research and advanced
      mammography quality control.

PMID- 17022244
TI  - A new real time filter for local exposure correction in panoramic radiographs.
AB  - A new real time filter for local exposure correction in panoramic radiographs is
      presented here. The filter, called PaRSEC, allows eliminating the exposure
      artifacts, mainly introduced by Automatic Exposure Control (AEC) systems. These
      artifacts reduce the image readability and its diagnostic utility. The PaRSEC
      filter operates a local exposure equalization, based on a reliable estimate of
      the column mean gray level. Qualitative and quantitative results are reported for
      typical panoramic radiographs. They show a complete removal of the artifacts. The
      method compares favorably with other classical methods targeted to exposure
      correction.

PMID- 17022246
TI  - The influence of noise in full Monte Carlo ML-EM and dual matrix reconstructions
      in positron emission tomography.
AB  - Monte Carlo (MC) simulations in positron emission tomography (PET) play an
      important role in detector modeling and algorithm testing. Whereas the
      simulations are widely used in a forward projection manner to accomplish this
      task, ideally they should be included into the reconstruction process itself. It
      is therefore desirable to investigate the convergence properties and the
      propagation of MC noise of these kinds of reconstruction algorithms. MC
      simulations were integrated into the maximum likelihood expectation maximization
      (ML-EM) algorithm in two different ways. In the full matrix approach the system
      matrix was calculated by running MC simulations, including scatter. This matrix
      was used in both the projector and the backprojector. In the dual matrix (DM)
      approach, MC simulations were used to incorporate scatter in the projector,
      whereas the backprojector only comprised attenuation. Repeated reconstructions
      with different MC seeds allowed a statistical analysis of the error at each
      iteration step and made it possible to investigate separately the propagation of
      the MC noise that was introduced by the sinogram, by the projector, and by the
      matrix. Both approaches resulted in similar images, but the DM approach with
      unmatched projector and backprojector yielded a faster initial convergence when
      compared to the ideal full matrix approach. The analysis of the noise sources for
      the modeled single ring scanner in full matrix reconstruction showed that the
      noise introduced by the matrix became comparable to the noise introduced by the
      sinogram when using a matrix that was simulated with 10,000 emissions/voxel.

PMID- 17022245
TI  - Low-dose megavoltage cone-beam computed tomography for lung tumors using a high
      efficiency image receptor.
AB  - We report on the capabilities of a low-dose megavoltage cone-beam computed
      tomography (MV CBCT) system. The high-efficiency image receptor consists of a
      photodiode array coupled to a scintillator composed of individual CsI crystals.
      The CBCT system uses the 6 MV beam from a linear accelerator. A synchronization
      circuit allows us to limit the exposure to one beam pulse [0.028 monitor units
      (MU)] per projection image. 150-500 images (4.2-13.9 MU total) are collected
      during a one-minute scan and reconstructed using a filtered backprojection
      algorithm. Anthropomorphic and contrast phantoms are imaged and the contrast-to
      noise ratio of the reconstruction is studied as a function of the number of
      projections and the error in the projection angles. The detector dose response is
      linear (R2 value 0.9989). A 2% electron density difference is discernible using
      460 projection images and a total exposure of 13 MU (corresponding to a maximum
      absorbed dose of about 12 cGy in a patient). We present first patient images
      acquired with this system. Tumors in lung are clearly visible and skeletal
      anatomy is observed in sufficient detail to allow reproducible registration with
      the planning kV CT images. The MV CBCT system is shown to be capable of obtaining
      good quality three-dimensional reconstructions at relatively low dose and to be
      clinically usable for improving the accuracy of radiotherapy patient positioning.

PMID- 17022247
TI  - A fourier analysis on the maximum acceptable grid size for discrete proton beam
      dose calculation.
AB  - We developed an analytical method for determining the maximum acceptable grid
      size for discrete dose calculation in proton therapy treatment plan optimization,
      so that the accuracy of the optimized dose distribution is guaranteed in the
      phase of dose sampling and the superfluous computational work is avoided. The
      accuracy of dose sampling was judged by the criterion that the continuous dose
      distribution could be reconstructed from the discrete dose within a 2% error
      limit. To keep the error caused by the discrete dose sampling under a 2% limit,
      the dose grid size cannot exceed a maximum acceptable value. The method was based
      on Fourier analysis and the Shannon-Nyquist sampling theorem as an extension of
      our previous analysis for photon beam intensity modulated radiation therapy [J.
      F. Dempsey, H. E. Romeijn, J. G. Li, D. A. Low, and J. R. Palta, Med. Phys. 32,
      380-388 (2005)]. The proton beam model used for the analysis was a near
      monoenergetic (of width about 1% the incident energy) and monodirectional
      infinitesimal (nonintegrated) pencil beam in water medium. By monodirection, we
      mean that the proton particles are in the same direction before entering the
      water medium and the various scattering prior to entrance to water is not taken
      into account. In intensity modulated proton therapy, the elementary intensity
      modulation entity for proton therapy is either an infinitesimal or finite sized
      beamlet. Since a finite sized beamlet is the superposition of infinitesimal
      pencil beams, the result of the maximum acceptable grid size obtained with
      infinitesimal pencil beam also applies to finite sized beamlet. The analytic
      Bragg curve function proposed by Bortfeld [T. Bortfeld, Med. Phys. 24, 2024-2033
      (1997)] was employed. The lateral profile was approximated by a depth dependent
      Gaussian distribution. The model included the spreads of the Bragg peak and the
      lateral profiles due to multiple Coulomb scattering. The dependence of the
      maximum acceptable dose grid size on the orientation of the beam with respect to
      the dose grid was also investigated. The maximum acceptable dose grid size
      depends on the gradient of dose profile and in turn the range of proton beam. In
      the case that only the phantom scattering was considered and that the beam was
      aligned with the dose grid, grid sizes from 0.4 to 6.8 mm were required for
      proton beams with ranges from 2 to 30 cm for 2% error limit at the Bragg peak
      point. A near linear relation between the maximum acceptable grid size and beam
      range was observed. For this analysis model, the resolution requirement was not
      significantly related to the orientation of the beam with respect to the grid.

PMID- 17022248
TI  - Surface preparation and coupling in plastic scintillator dosimetry.
AB  - One way to improve the performance of scintillation dosimeters is to increase the
      light-collection efficiency at the coupling interfaces of the detector system. We
      performed a detailed study of surface preparation of scintillating fibers and
      their coupling with clear optical fibers to minimize light loss and increase the
      amount of light collected. We analyzed fiber-surface polishing with aluminum
      oxide sheets, coating fibers with magnesium oxide, and the use of eight different
      coupling agents (air, three optical gels, an optical curing agent, ultraviolet
      light, cyanoacrylate glue, and acetone). We prepared 10 scintillating fiber and
      clear optical fiber light guide samples to test different coupling methods. To
      test the coupling, we first cut both the scintillating fiber and the clear
      optical fiber. Then, we cleaned and polished both ends of both fibers. Finally,
      we coupled the scintillating fiber with the clear optical fiber in either a
      polyethylene jacket or a V-grooved support depending on the coupling agent used.
      To produce more light, we used an ultraviolet lamp to stimulate scintillation. A
      typical series of similar couplings showed a standard deviation in light
      collection efficiency of 10%. This can be explained by differences in the surface
      preparation quality and alignment of the scintillating fiber with the clear
      optical fiber. Absence of surface polishing reduced the light collection by
      approximately 40%, and application of magnesium oxide on the proximal end of the
      scintillating fiber increased the amount of light collected from the optical
      fiber by approximately 39%. Of the coupling agents, we obtained the best results
      using one of the optical gels. Because a large amount of the light produced
      inside a scintillator is usually lost, better light-collection efficiency will
      result in improved sensitivity.

PMID- 17022249
TI  - Delay differential equations and the dose-time dependence of early radiotherapy
      reactions.
AB  - The dose-time dependence of early radiotherapy reactions impacts on the design of
      accelerated fractionation schedules--oral mucositis, for example, can be dose
      limiting for short treatments designed to avoid tumor repopulation. In this paper
      a framework for modeling early reaction dose-time dependence is developed.
      Variation of stem cell number with time after the start of a radiation schedule
      is modeled using a first-order delay differential equation (DDE), motivated by
      experimental observations linking the speed of compensatory proliferation in
      early reacting tissues to the degree of tissue damage. The modeling suggests that
      two types of early reaction radiation response are possible, stem cell numbers
      either monotonically approaching equilibrium plateau levels or overshooting
      before returning to equilibrium. Several formulas have been derived from the
      delay differential equation, predicting changes in isoeffective total radiation
      dose with schedule duration for different types of fractionation scheme. The
      formulas have been fitted to a wide range of published animal early reaction
      data, the fits all implying a degree of overshoot. Results are presented
      illustrating the scope of the delay differential model: most of the data are
      fitted well, although the model struggles with a few datasets measured for
      schedules with distinctive dose-time patterns. Ways of extending the current
      model to cope with these particular dose-time patterns are briefly discussed. The
      DDE approach is conceptually more complex than earlier descriptive dose-time
      models but potentially more powerful. It can be used to study issues not
      addressed by simpler models, such as the likely effects of increasing or
      decreasing the dose-per-day over time, or of splitting radiation courses into
      intense segments separated by gaps. It may also prove useful for modeling the
      effects of chemoirradiation.

PMID- 17022250
TI  - Measurement of LINAC 90 degrees head leakage radiation TVL values.
AB  - One of the key components in modern LINAC room shielding design is the amount of
      90 degrees head leakage radiation levels. With the general clinical acceptance of
      intensity-modulated radiation therapy (IMRT) technique, accurate knowledge of
      this quantity has become even more important. Measurement of 90 degrees head
      leakage radiation of medical linear accelerators can be technically challenging
      due to the low dose rate causing poor signal-to-noise ratios in most detectors.
      90 degrees leakage tenth-value layer (TVL) values in concrete have not been
      reported for the Elekta linear accelerators. This report describes our
      measurements of 90 degrees leakage TVL values for 6, 10, and 18 MV x-ray beams
      for an Elekta Precise Treatment System. A large-volume (1000 cm3) unpressurized
      ionization chamber and a high sensitivity electrometer, together with a separate
      chamber bias power supply, were used in these measurements in order to maximize
      the signal-to-noise ratio. A lead enclosure, of minimum thickness 10 cm, was
      constructed inside the treatment room to house the ion chamber to reduce the
      influence of room-scattered radiation. A square aperture of 10 X 10 cm2 area was
      left in the shield and aimed towards the accelerator head. Measurements were
      performed with the chamber placed at approximately 2 m from the accelerator
      isocenter. Concrete slabs with individual dimensions of approximately 40 X 40 cm2
      cross-sectional area and 5 cm thickness were placed between the accelerator head
      and the ion chamber for these measurements. The measurements were performed with
      total concrete thickness of up to 80 cm, so that values up to the third TVL were
      measured. These measurements showed thatthe first concrete TVL values are 22, 23,
      and 28 cm (8.6, 9.1, and 10.5 in.) for 6, 10, and 18 MV beams, while the average
      of the first 3 TVL's were 25, 26, and 29 cm (9.9, 10.2, and 11.5 in.). Measured
      values agreed to within 10% of previously reported values for Varian linear
      accelerators for equivalent radiation beam qualities.

PMID- 17022251
TI  - Relevance of 2D radiographic texture analysis for the assessment of 3D bone micro
      architecture.
AB  - Although the diagnosis of osteoporosis is mainly based on dual x-ray
      absorptiometry, it has been shown that trabecular bone micro-architecture is also
      an important factor in regard to fracture risk. In vivo, techniques based on high
      resolution x-ray radiography associated to texture analysis have been proposed to
      investigate bone micro-architecture, but their relevance for giving pertinent 3D
      information is unclear. Thirty-three calcaneus and femoral neck bone samples
      including the cortical shells (diameter: 14 mm, height: 30-40 mm) were imaged
      using 3D-synchrotron x-ray micro-CT at the ESRF. The 3D reconstructed images with
      a cubic voxel size of 15 microm were further used for two purposes: (1)
      quantification of three-dimensional trabecular bone micro-architecture, (2)
      simulation of realistic x-ray radiographs under different acquisition conditions.
      The simulated x-ray radiographs were then analyzed using a large variety of
      texture analysis methods (co-occurrence, spectral density, fractal, morphology,
      etc.). The range of micro-architecture parameters was in agreement with previous
      studies and rather large, suggesting that the population was representative. More
      than 350 texture parameters were tested. A small number of them were selected
      based on their correlation to micro-architectural morphometric parameters. Using
      this subset of texture parameters, multiple regression allowed one to predict up
      to 93% of the variance of micro-architecture parameters using three texture
      features. 2D texture features predicting 3D micro-architecture parameters other
      than BV/TV were identified. The methodology proposed for evaluating the
      relationships between 3D micro-architecture and 2D texture parameters may also be
      used for optimizing the conditions for radiographic imaging. Further work will
      include the application of the method to physical radiographs. In the future,
      this approach could be used in combination with DXA to refine osteoporosis
      diagnosis.

PMID- 17022252
TI  - Analysis of the kinestatic charge detection system as a high detective quantum
      efficiency electronic portal imaging device.
AB  - Megavoltage x-ray imaging suffers from reduced image quality due to low
      differential x-ray attenuation and large Compton scatter compared with
      kilovoltage imaging. Notwithstanding this, electronic portal imaging devices
      (EPIDs) are now widely used in portal verification in radiotherapy as they offer
      significant advantages over film, including immediate digital imaging and
      superior contrast range. However video-camera-based EPIDs (VEPIDs) are limited by
      problems of low light collection efficiency and significant light scatter,
      leading to reduced contrast and spatial resolution. Indirect and direct detection
      based flat-panel EPIDs have been developed to overcome these limitations. While
      flat-panel image quality has been reported to exceed that achieved with portal
      film, these systems have detective quantum efficiency (DQE) limited by the thin
      detection medium and are sensitive to radiation damage to peripheral read-out
      electronics. An alternative technology for high-quality portal imaging is
      presented here: kinesatic charge detection (KCD). The KCD is a scanning tri
      electrode ion-chamber containing high-pressure noble gas (xenon at 100 atm) used
      in conjunction with a strip-collimated photon beam. The chamber is scanned across
      the patient, and an external electric field is used to regulate the cation drift
      velocity. By matching the scanning velocity with that of the cation (i.e., ion)
      drift velocity, the cations remain static in the object frame of reference,
      allowing temporal integration of the signal. The KCD offers several advantages as
      a portal imaging system. It has a thick detector geometry with an active
      detection depth of 6.1 cm, compared to the sub-millimeter thickness of the
      phosphor layer in conventional phosphor screens, leading to an order of magnitude
      advantage in quantum efficiency (>0.3). The unique principle of and the use of
      the scanning strip-collimated x-ray beam provide further integration of charges
      in time, reduced scatter, and a significantly reduced imaging dose, enhancing the
      imaging signal-to-noise ratio (SNR) and leading to high DQE. While thick
      detectors usually suffer from reduced spatial resolution, the KCD provides good
      spatial resolution due to high gas pressure that limits the spread of scattered
      electrons, and a strip-collimated beam that significantly reduces the inclusion
      of scatter in the imaging signal. A 10 cm wide small-field-of-view (SFOV)
      prototype of the KCD is presented with a complete analysis of its imaging
      performance. Measurements of modulation transfer function (MTF), noise power
      spectrum (NPS), and DQE were in good agreement with Monte Carlo simulations.
      Imaging signal loss from recombination within the KCD chamber was measured at
      different gas pressures, ion drift velocities, and strip-collimation widths.
      Image quality for the prototype KCD was also observed with anthropomorphic
      phantom imaging in comparison with various commercial and research portal imaging
      systems, including VEPID, flat-panel imager, and conventional and high contrast
      film systems. KCD-based imaging provided very good contrast and good spatial
      resolution at very low imaging dose (0.1 cGy per image). For the prototype KCD,
      measurements yielded DQE(0)=0.19 and DQE(1 cy/mm)=0.004.

PMID- 17022253
TI  - Comparison of synchrotron radiation and conventional x-ray microcomputed
      tomography for assessing trabecular bone microarchitecture of human femoral
      heads.
AB  - Microcomputed tomography (microCT) produces three-dimensional (3D) images of
      trabecular bone. We compared conventional microCT (CmicroCT) with a polychromatic
      x-ray cone beam to synchrotron radiation (SR) microCT with a monochromatic
      parallel beam for assessing trabecular bone microarchitecture of 14 subchondral
      femoral head specimens from patients with osteoarthritis (n=10) or osteoporosis
      (n=4). SRmicroCT images with a voxel size of 10.13 microm were reconstructed from
      900 2D radiographic projections (angular step, 0.2 degrees). CmicroCT images with
      a voxel size of 10.77 microm were reconstructed from 205, 413, and 825
      projections obtained using angular steps of 0.9 degrees, 0.45 degrees, and 0.23
      degrees, respectively. A single threshold was used to binarize the images. We
      computed bone volume/ tissue volume (BV/TV), bone surface/bone volume (BS/BV),
      trabecular number (Tb.N), trabecular thickness (Tb.Th and Tb.Th*), trabecular
      spacing (Tb.Sp), degree of anisotropy (DA), and Euler density. With the 0.9
      degrees angular step, all CmicroCT values were significantly different from
      SRmicroCT values. With the 0.23 degrees and 0.45 degrees rotation steps, BV/TV,
      Tb.Th, and BS/BV by CmicroCT differed significantly from the values by SRmicroCT.
      The error due to slice matching (visual site matching +/- 10 slices) was within
      1% for most parameters. Compared to SRmicroCT, BV/TV, Tb.Sp, and Tb.Th by
      CmicroCT were underestimated, whereas Tb.N and Tb. Th* were overestimated. A
      Bland and Altman plot showed no bias for Tb.N or DA. Bias was -0.8 +/- 1.0%, +5.0
      +/- 1.1 microm, -5.9 +/- 6.3 microm, and -5.7 +/- 29.1 microm for BV/TV, Tb.Th*,
      Tb.Th, and Tb.Sp, respectively, and the differences did not vary over the range
      of values. Although systematic differences were noted between SRmicroCT and
      CmicroCT values, correlations between the techniques were high and the
      differences would probably not change the discrimination between study groups.
      CmicroCT provides a reliable 3D assessment of human defatted bone when working at
      the 0.23 degrees or 0.45 degrees rotation step; the 0.9 degrees rotation step may
      be insufficiently accurate for morphological bone analysis.

PMID- 17022254
TI  - Ballistics projectile image analysis for firearm identification.
AB  - This paper is based upon the observation that, when a bullet is fired, it creates
      characteristic markings on the cartridge case and projectile. From these
      markings, over 30 different features can be distinguished, which, in combination,
      produce a "fingerprint" for a firearm. By analyzing features within such a set of
      firearm fingerprints, it will be possible to identify not only the type and model
      of a firearm, but also each and every individual weapon just as effectively as
      human fingerprint identification. A new analytic system based on the fast Fourier
      transform for identifying projectile specimens by the line-scan imaging technique
      is proposed in this paper. This paper develops optical, photonic, and mechanical
      techniques to map the topography of the surfaces of forensic projectiles for the
      purpose of identification. Experiments discussed in this paper are performed on
      images acquired from 16 various weapons. Experimental results show that the
      proposed system can be used for firearm identification efficiently and precisely
      through digitizing and analyzing the fired projectiles specimens.

PMID- 17022255
TI  - Optimal spatial adaptation for patch-based image denoising.
AB  - A novel adaptive and patch-based approach is proposed for image denoising and
      representation. The method is based on a pointwise selection of small image
      patches of fixed size in the variable neighborhood of each pixel. Our
      contribution is to associate with each pixel the weighted sum of data points
      within an adaptive neighborhood, in a manner that it balances the accuracy of
      approximation and the stochastic error, at each spatial position. This method is
      general and can be applied under the assumption that there exists repetitive
      patterns in a local neighborhood of a point. By introducing spatial adaptivity,
      we extend the work earlier described by Buades et al. which can be considered as
      an extension of bilateral filtering to image patches. Finally, we propose a
      nearly parameter-free algorithm for image denoising. The method is applied to
      both artificially corrupted (white Gaussian noise) and real images and the
      performance is very close to, and in some cases even surpasses, that of the
      already published denoising methods.

PMID- 17022256
TI  - Discriminative analysis of lip motion features for speaker identification and
      speech-reading.
AB  - There have been several studies that jointly use audio, lip intensity, and lip
      geometry information for speaker identification and speech-reading applications.
      This paper proposes using explicit lip motion information, instead of or in
      addition to lip intensity and/or geometry information, for speaker identification
      and speech-reading within a unified feature selection and discrimination analysis
      framework, and addresses two important issues: 1) Is using explicit lip motion
      information useful, and, 2) if so, what are the best lip motion features for
      these two applications? The best lip motion features for speaker identification
      are considered to be those that result in the highest discrimination of
      individual speakers in a population, whereas for speech-reading, the best
      features are those providing the highest phoneme/word/phrase recognition rate.
      Several lip motion feature candidates have been considered including dense motion
      features within a bounding box about the lip, lip contour motion features, and
      combination of these with lip shape features. Furthermore, a novel two-stage,
      spatial, and temporal discrimination analysis is introduced to select the best
      lip motion features for speaker identification and speech-reading applications.
      Experimental results using an hidden-Markov-model-based recognition system
      indicate that using explicit lip motion information provides additional
      performance gains in both applications, and lip motion features prove more
      valuable in the case of speech-reading application.

PMID- 17022257
TI  - Oriented wavelet transform for image compression and denoising.
AB  - In this paper, we introduce a new transform for image processing, based on
      wavelets and the lifting paradigm. The lifting steps of a unidimensional wavelet
      are applied along a local orientation defined on a quincunx sampling grid. To
      maximize energy compaction, the orientation minimizing the prediction error is
      chosen adaptively. A fine-grained multiscale analysis is provided by iterating
      the decomposition on the low-frequency band. In the context of image compression,
      the multiresolution orientation map is coded using a quad tree. The rate
      allocation between the orientation map and wavelet coefficients is jointly
      optimized in a rate-distortion sense. For image denoising, a Markov model is used
      to extract the orientations from the noisy image. As long as the map is
      sufficiently homogeneous, interesting properties of the original wavelet are
      preserved such as regularity and orthogonality. Perfect reconstruction is ensured
      by the reversibility of the lifting scheme. The mutual information between the
      wavelet coefficients is studied and compared to the one observed with a separable
      wavelet transform. The rate-distortion performance of this new transform is
      evaluated for image coding using state-of-the-art subband coders. Its performance
      in a denoising application is also assessed against the performance obtained with
      other transforms or denoising methods.

PMID- 17022258
TI  - Asymptotic global confidence regions for 3-D parametric shape estimation in
      inverse problems.
AB  - This paper derives fundamental performance bounds for statistical estimation of
      parametric surfaces embedded in R3. Unlike conventional pixel-based image
      reconstruction approaches, our problem is reconstruction of the shape of binary
      or homogeneous objects. The fundamental uncertainty of such estimation problems
      can be represented by global confidenceregions, which facilitate geometric
      inference and optimization ofthe imaging system. Compared to our previous work on
      global confidence region analysis for curves [two-dimensional (2-D) shapes],
      computation of the probability that the entire surface estimate lies within the
      confidence region is more challenging because a surface estimate is an
      inhomogeneous random field continuously indexed by a 2-D variable. We derive an
      asymptotic lower bound to this probability by relating it to the exceedence
      probability of a higher dimensional Gaussian random field, which can, in turn, be
      evaluated using the tube formula due to Sun. Simulation results demonstrate the
      tightness of the resulting bound and the usefulness of the three-dimensional
      global confidence region approach.

PMID- 17022259
TI  - Fusion of Hidden Markov Random Field models and its Bayesian estimation.
AB  - In this paper, we present a Hidden Markov Random Field (HMRF) data-fusion model.
      The proposed model is applied to the segmentation of natural images based on the
      fusion of colors and textons into Julesz ensembles. The corresponding
      Exploration/ Selection/Estimation (ESE) procedure for the estimation of the
      parameters is presented. This method achieves the estimation of the parameters of
      the Gaussian kernels, the mixture proportions, the region labels, the number of
      regions, and the Markov hyper-parameter. Meanwhile, we present a new proof of the
      asymptotic convergence of the ESE procedure, based on original finite time bounds
      for the rate of convergence.

PMID- 17022260
TI  - Robust and efficient image alignment based on relative gradient matching.
AB  - In this paper, we present a robust image alignment algorithm based on matching of
      relative gradient maps. This algorithm consists of two stages; namely, a learning
      based approximate pattern search and an iterative energy-minimization procedure
      for matching relative image gradient. The first stage finds some candidate poses
      of the pattern from the image through a fast nearest-neighbor search of the best
      match of the relative gradient features computed from training database of
      feature vectors, which are obtained from the synthesis of the geometrically
      transformed template image with the transformation parameters uniformly sampled
      from a given transformation parameter space. Subsequently, the candidate poses
      are further verified and refined by matching the relative gradient images through
      an iterative energy- minimization procedure. This approach based on the matching
      of relative gradients is robust against nonuniform illumination variations.
      Experimental results on both simulated and real images are shown to demonstrate
      superior efficiency and robustness of the proposed algorithm over the
      conventional normalized correlation method.

PMID- 17022261
TI  - Color demosaicing using variance of color differences.
AB  - This paper presents an adaptive demosaicing algorithm. Missing green samples are
      first estimated based on the variances of the color differences along different
      edge directions. The missing red and blue components are then estimated based on
      the interpolated green plane. This algorithm can effectively preserve the details
      in texture regions and, at the same time, it can significantly reduce the color
      artifacts. As compared with the latest demosaicing algorithms, the proposed
      algorithm produces the best average demosaicing performance both objectively and
      subjectively.

PMID- 17022262
TI  - An optimal fuzzy system for color image enhancement.
AB  - A Gaussian membership function is proposed to fuzzify the image information in
      spatial domain. We introduce a global contrast intensification operator (GINT),
      which contains three parameters, viz., intensification parameter t, fuzzifier fh,
      and the crossover point mu(c), for enhancement of color images. We define fuzzy
      contrast-based quality factor Qf and entropy-based quality factor Qe and the
      corresponding visual factors for the desired appearance of images. By minimizing
      the fuzzy entropy of the image information with respect to these quality factors,
      the parameters t, fh, and mu(c) are calculated globally. By using the proposed
      technique, a visible improvement in the image quality is observed for under
      exposed images, as the entropy of the output image is decreased. The terminating
      criterion is decided by both the visual and quality factors. For over exposed and
      under plus over exposed images, the proposed fuzzification function needs to be
      modified by taking maximum intensity as the fourth parameter. The type of the
      images is indicated by the visual factor which is less than 1 for under exposed
      images and more than 1 for over exposed images.

PMID- 17022263
TI  - Linear, worst-case estimators for denoising quantization noise in transform coded
      images.
AB  - Transform-coded images exhibit distortions that fall outside of the assumptions
      of traditional denoising techniques. In this paper, we use tools from robust
      signal processing to construct linear, worst-case estimators for the denoising of
      transform compressed images. We show that while standard denoising is
      fundamentally determined by statistical models for images alone, the distortions
      induced by transform coding are heavily dependent on the structure of the
      transform used. Our method, thus, uses simple models for the image and for the
      quantization error, with the latter capturing the transform dependency. Based on
      these models, we derive optimal, linear estimators of the original image that are
      optimal in the mean-squared error sense for the worst-case cross correlation
      between the original and the quantization error. Our construction is transform
      agnostic and is applicable to transforms from block discrete cosine transforms to
      wavelets. Furthermore, our approach is applicable to different types of image
      statistics and can also serve as an optimization tool for the design of
      transforms/quantizers. Through the interaction of the source and quantizer
      models, our work provides useful insights and is instrumental in identifying and
      removing quantization artifacts from general signals coded with general
      transforms. As we decouple the modeling and processing steps, we allow for the
      construction of many different types of estimators depending on the desired
      sophistication and available computational complexity. In the low end of this
      spectrum, our lookup table based estimator, which can be deployed in low
      complexity environments, provides competitive PSNR values with some of the best
      results in the literature.

PMID- 17022264
TI  - Bayesian restoration using a new nonstationary edge-preserving image prior.
AB  - In this paper, we propose a class of image restoration algorithms based on the
      Bayesian approach and a new hierarchical spatially adaptive image prior. The
      proposed prior has the following two desirable features. First, it models the
      local image discontinuities in different directions with a model which is
      continuous valued. Thus, it preserves edges and generalizes the on/off (binary)
      line process idea used in previous image priors within the context of Markov
      random fields (MRFs). Second, it is Gaussian in nature and provides estimates
      that are easy to compute. Using this new hierarchical prior, two restoration
      algorithms are derived. The first is based on the maximum a posteriori principle
      and the second on the Bayesian methodology. Numerical experiments are presented
      that compare the proposed algorithms among themselves and with previous
      stationary and non stationary MRF-based with line process algorithms. These
      experiments demonstrate the advantages of the proposed prior.

PMID- 17022265
TI  - Multidimensional multichannel FIR deconvolution using Grobner bases.
AB  - We present a new method for general multidimensional multichannel deconvolution
      with finite impulse response (FIR) convolution and deconvolution filters using
      Grobner bases. Previous work formulates the problem of multichannel FIR
      deconvolution as the construction of a left inverse of the convolution matrix,
      which is solved by numerical linear algebra. However, this approach requires the
      prior information of the support of deconvolution filters. Using algebraic
      geometry and Grobner bases, we find necessary and sufficient conditions for the
      existence of exact deconvolution FIR filters and propose simple algorithms to
      find these deconvolution filters. The main contribution of our work is to extend
      the previous Grobner basis results on multidimensional multichannel deconvolution
      for polynomial or causal filters to general FIR filters. The proposed algorithms
      obtain a set of FIR deconvolution filters with a small number of nonzero
      coefficients (a desirable feature in the impulsive noise environment) and do not
      require the prior information of the support. Moreover, we provide a complete
      characterization of all exact deconvolution FIR filters, from which good FIR
      deconvolution filters under the additive white noise environment are found.
      Simulation results show that our approaches achieve good results under different
      noise settings.

PMID- 17022266
TI  - Estimation of two-dimensional affine transformations through polar curve matching
      and its application to image mosaicking and remote-sensing data registration.
AB  - This paper presents a new and effective method for estimating two-dimensional
      affine transformations and its application to image registration. The method is
      based on matching polar curves obtained from the radial projections of the image
      energies, defined as the squared magnitudes of their Fourier transforms. Such
      matching is formulated as a simple minimization problem whose optimal solution is
      found with the Levenberg-Marquardt algorithm. The analysis of affine
      transformations in the frequency domain exploits the well-known property whereby
      the translational displacement in this domain can be factored out and separately
      estimated through phase correlation after the four remaining degrees of freedom
      of the affine warping have been determined. Another important contribution of
      this paper, emphasized through one example of image mosaicking and one example of
      remote sensing image registration, consists in showing that affine motion can be
      accurately estimated by applying our algorithm to the shapes of macrofeatures
      extracted from the images to register. The excellent performance of the algorithm
      is also shown through a synthetic example of motion estimation and its comparison
      with another standard registration technique.

PMID- 17022267
TI  - Three-dimensional nonlinear invisible boundary detection.
AB  - The human vision system can discriminate regions which differ up to the second
      order statistics only. We present an algorithm designed to reveal "hidden"
      boundaries in gray level images, by computing gradients in higher order
      statistics of the data. We demonstrate it by applying it to the identification of
      possible "hidden" boundaries of glioblastomas as manifest themselves in three
      dimensional (3-D) MRI scans, using a model driven approach. We also demonstrate
      the method using a nonmodel driven approach where we have no prior information
      about the location of possible boundaries. In this case, we use 3-D MRI data
      concerning schizophrenic patients and normal controls.

PMID- 17022268
TI  - Hierarchical stochastic image grammars for classification and segmentation.
AB  - We develop a new class of hierarchical stochastic image models called spatial
      random trees (SRTs) which admit polynomial-complexity exact inference algorithms.
      Our framework of multitree dictionaries is the starting point for this
      construction. SRTs are stochastic hidden tree models whose leaves are associated
      with image data. The states at the tree nodes are random variables, and, in
      addition, the structure of the tree is random and is generated by a probabilistic
      grammar. We describe an efficient recursive algorithm for obtaining the maximum a
      posteriori estimate of both the tree structure and the tree states given an
      image. We also develop an efficient procedure for performing one iteration of the
      expectation-maximization algorithm and use it to estimate the model parameters
      from a set of training images. We address other inference problems arising in
      applications such as maximization of posterior marginals and hypothesis testing.
      Our models and algorithms are illustrated through several image classification
      and segmentation experiments, ranging from the segmentation of synthetic images
      to the classification of natural photographs and the segmentation of scanned
      documents. In each case, we show that our method substantially improves accuracy
      over a variety of existing methods.

PMID- 17022269
TI  - Local image registration by adaptive filtering.
AB  - We propose a new adaptive filtering framework for local image registration, which
      compensates for the effect of local distortions/displacements without explicitly
      estimating a distortion/displacement field. To this effect, we formulate local
      image registration as a two-dimensional (2-D) system identification problem with
      spatially varying system parameters. We utilize a 2-D adaptive filtering
      framework to identify the locally varying system parameters, where a new block
      adaptive filtering scheme is introduced. We discuss the conditions under which
      the adaptive filter coefficients conform to a local displacement vector at each
      pixel. Experimental results demonstrate that the proposed 2-D adaptive filtering
      framework is very successful in modeling and compensation of both local
      distortions, such as Stirmark attacks, and local motion, such as in the presence
      of a parallax field. In particular, we show that the proposed method can provide
      image registration to: a) enable reliable detection of watermarks following a
      Stirmark attack in nonblind detection scenarios, b) compensate for lens
      distortions, and c) align multiview images with nonparametric local motion.

PMID- 17022270
TI  - Image and texture segmentation using local spectral histograms.
AB  - We present a method for segmenting images consisting of texture and nontexture
      regions based on local spectral histograms. Defined as a vector consisting of
      marginal distributions of chosen filter responses, local spectral histograms
      provide a feature statistic for both types of regions. Using local spectral
      histograms of homogeneous regions, we decompose the segmentation process into
      three stages. The first is the initial classification stage, where probability
      models for homogeneous texture and nontexture regions are derived and an initial
      segmentation result is obtained by classifying local windows. In the second
      stage, we give an algorithm that iteratively updates the segmentation using the
      derived probability models. The third is the boundary localization stage, where
      region boundaries are localized by building refined probability models that are
      sensitive to spatial patterns in segmented regions. We present segmentation
      results on texture as well as nontexture images. Our comparison with other
      methods shows that the proposed method produces more accurate segmentation
      results.

PMID- 17022271
TI  - A fast and effective model for wavelet subband histograms and its application in
      texture image retrieval.
AB  - This paper presents a novel, effective, and efficient characterization of wavelet
      subbands by bit-plane extractions. Each bit plane is associated with a
      probability that represents the frequency of 1-bit occurrence, and the
      concatenation of all the bit-plane probabilities forms our new image signature.
      Such a signature can be extracted directly from the code-block code-stream,
      rather than from the de-quantized wavelet coefficients, making our method
      particularly adaptable for image retrieval in the compression domain such as
      JPEG2000 format images. Our signatures have smaller storage requirement and lower
      computational complexity, and yet, experimental results on texture image
      retrieval show that our proposed signatures are much more cost effective to
      current state-of-the-art methods including the generalized Gaussian density
      signatures and histogram signatures.

PMID- 17022272
TI  - The nonsubsampled contourlet transform: theory, design, and applications.
AB  - In this paper, we develop the nonsubsampled contourlet transform (NSCT) and study
      its applications. The construction proposed in this paper is based on a
      nonsubsampled pyramid structure and nonsubsampled directional filter banks. The
      result is a flexible multiscale, multidirection, and shift-invariant image
      decomposition that can be efficiently implemented via the a trous algorithm. At
      the core of the proposed scheme is the nonseparable two-channel nonsubsampled
      filter bank (NSFB). We exploit the less stringent design condition of the NSFB to
      design filters that lead to a NSCT with better frequency selectivity and
      regularity when compared to the contourlet transform. We propose a design
      framework based on the mapping approach, that allows for a fast implementation
      based on a lifting or ladder structure, and only uses one-dimensional filtering
      in some cases. In addition, our design ensures that the corresponding frame
      elements are regular, symmetric, and the frame is close to a tight one. We assess
      the performance of the NSCT in image denoising and enhancement applications. In
      both applications the NSCT compares favorably to other existing methods in the
      literature.

PMID- 17022273
TI  - Motion compensation via redundant-wavelet multihypothesis.
AB  - Multihypothesis motion compensation has been widely used in video coding with
      previous attention focused on techniques employing predictions that are diverse
      spatially or temporally. In this paper, the multihypothesis concept is extended
      into the transform domain by using a redundant wavelet transform to produce
      multiple predictions that are diverse in transform phase. The corresponding
      multiple-phase inverse transform implicitly combines the phase-diverse
      predictions into a single spatial-domain prediction for motion compensation. The
      performance advantage of this redundant-wavelet-multihypothesis approach is
      investigated analytically, invoking the fact that the multiple-phase inverse
      involves a projection that significantly reduces the power of a dense-motion
      residual modeled as additive noise. The analysis shows that redundant-wavelet
      multihypothesis is capable of up to a 7-dB reduction in prediction-residual
      variance over an equivalent single-phase, single-hypothesis approach.
      Experimental results substantiate the performance advantage for a block-based
      implementation.

PMID- 17022274
TI  - Embedded multiple description coding of video.
AB  - Real-time delivery of video over best-effort error-prone packet networks requires
      scalable erasure-resilient compression systems in order to 1) meet the users'
      requirements in terms of quality, resolution, and frame-rate; 2) dynamically
      adapt the rate to the available channel capacity; and 3) provide robustness to
      data losses, as retransmission is often impractical. Furthermore, the employed
      erasure-resilience mechanisms should be scalable in order to adapt the degree of
      resiliency against transmission errors to the varying channel conditions. Driven
      by these constraints, we propose in this paper a novel design for scalable
      erasure-resilient video coding that couples the compression efficiency of the
      open-loop architecture with the robustness provided by multiple description
      coding. In our approach, scalability and packet-erasure resilience are jointly
      provided via embedded multiple description scalar quantization. Furthermore, a
      novel channel-aware rate-allocation technique is proposed that allows for shaping
      on-the-fly the output bit rate and the degree of resiliency without resorting to
      channel coding. As a result, robustness to data losses is traded for better
      visual quality when transmission occurs over reliable channels, while erasure
      resilience is introduced when noisy links are involved. Numerical results clearly
      demonstrate the advantages of the proposed approach over equivalent codec
      instantiations employing 1) no erasure-resilience mechanisms, 2) erasure
      resilience with nonscalable redundancy, or 3) data-partitioning principles.

PMID- 17022275
TI  - Uncertainty estimation by convolution using spatial statistics.
AB  - Kriging has proven to be a useful tool in image processing since it behaves,
      under regular sampling, as a convolution. Convolution kernels obtained with
      kriging allow noise filtering and include the effects of the random fluctuations
      of the experimental data and the resolution of the measuring devices. The
      uncertainty at each location of the image can also be determined using kriging.
      However, this procedure is slow since, currently, only matrix methods are
      available. In this work, we compare the way kriging performs the uncertainty
      estimation with the standard statistical technique for magnitudes without spatial
      dependence. As a result, we propose a much faster technique, based on the
      variogram, to determine the uncertainty using a convolutional procedure. We check
      the validity of this approach by applying it to one-dimensional images obtained
      in diffractometry and two-dimensional images obtained by shadow moire.

PMID- 17022276
TI  - Improvement of color video demosaicking in temporal domain.
AB  - Color demosaicking is critical to the image quality of digital still and video
      cameras that use a single-sensor array. Limited by the mosaic sampling pattern of
      the color filter array (CFA), color artifacts may occur in a demosaicked image in
      areas of high-frequency and/or sharp color transition structures. However, a
      color digital video camera captures a sequence of mosaic images and the temporal
      dimension of the color signals provides a rich source of information about the
      scene via camera and object motions. This paper proposes an inter-frame
      demosaicking approach to take advantage of all three forms of pixel correlations:
      spatial, spectral, and temporal. By motion estimation and statistical data fusion
      between adjacent mosaic frames, the new approach can remove much of the color
      artifacts that survive intra-frame demosaicking and also improve tone
      reproduction accuracy. Empirical results show that the proposed inter-frame
      demosaicking approach consistently outperforms its intra-frame counterparts both
      in peak signal-to-noise measure and subjective visual quality.

PMID- 17022277
TI  - High-quality MRC document coding.
AB  - The mixed raster content (MRC) model can be used to implement highly effective
      document compression algorithms. MRC document coders are typically based on the
      use of a binary mask layer that efficiently encodes the text and graphic content.
      However, while many MRC-based methods can yield much higher compression ratios
      than conventional color image compression methods, the binary representation
      tends to distort fine document details, such as thin lines and text edges. In
      this paper, we propose a method for encoding and decoding the binary mask layer
      that substantially improves the decoded document fidelity of text and graphics at
      a fixed bit rate. This method, which we call resolution-enhanced rendering (RER),
      works by adaptively dithering the encoded binary mask, and then applying a
      nonlinear predictor to decode a gray level mask at the same resolution. Both the
      dithering and nonlinear prediction algorithms are jointly optimized to produce
      the minimal distortion rendering. In addition, we introduce a second method,
      interpolative RER (IRER), which incorporates interpolation into the MRC decoder.
      The IRER method increases the compression ratio by allowing a high-resolution
      document to be coded at lower resolutions. We present experimental results
      illustrating the performance of our RER/IRER methods and comparing them to some
      existing MRC-based compression algorithms.

PMID- 17022278
TI  - Generalized manifold-ranking-based image retrieval.
AB  - In this paper, we propose a general transductive learning framework named
      generalized manifold-ranking-based image retrieval (gMRBIR) for image retrieval.
      Comparing with an existing transductive learning method named MRBIR [12], our
      method could work well whether or not the query image is in the database; thus,
      it is more applicable for real applications. Given a query image, gMRBIR first
      initializes a pseudo seed vector based on neighborhood relationship and then
      spread its scores via manifold ranking to all the unlabeled images in the
      database. Furthermore, in gMRBIR, we also make use of relevance feedback and
      active learning to refine the retrieval result so that it converges to the query
      concept as fast as possible. Systematic experiments on a general-purpose image
      database consisting of 5,000 Corel images demonstrate the superiority of gMRBIR
      over state-of-the-art techniques.

PMID- 17022279
TI  - A deformable grid-matching approach for microarray images.
AB  - A fundamental step of microarray image analysis is the detection of the grid
      structure for the accurate location of each spot, representing the state of a
      given gene in a particular experimental condition. This step is known as gridding
      and belongs to the class of deformable grid matching problems which are well
      known in literature. Most of the available microarray gridding approaches require
      human intervention; for example, to specify landmarks, some points in the spot
      grid, or even to precisely locate individual spots. Automating this part of the
      process can allow high throughput analysis. This paper focuses on the development
      of a fully automated procedure for the problem of automatic microarray gridding.
      It is grounded on the Bayesian paradigm and on image analysis techniques. The
      procedure has two main steps. The first step, based on the Radon transform, is
      aimed at generating a grid hypothesis; the second step accounts for local grid
      deformations. The accuracy and properties of the procedure are quantitatively
      assessed over a set of synthetic and real images; the results are compared with
      well-known methods available from the literature.

PMID- 17022280
TI  - Multiscale fragile watermarking based on the Gaussian mixture model.
AB  - In this paper, a new multiscale fragile watermarking scheme based on the Gaussian
      mixture model (GMM) is presented. First, a GMM is developed to describe the
      statistical characteristics of images in the wavelet domain and an expectation
      maximization algorithm is employed to identify GMM model parameters. With wavelet
      multiscale subspaces being divided into watermarking blocks, the GMM model
      parameters of different watermarking blocks are adjusted to form certain
      relationships, which are employed for the presented new fragile watermarking
      scheme for authentication. An optimal watermark embedding method is developed to
      achieve minimum watermarking distortion. A secret embedding key is designed to
      securely embed the fragile watermarks so that the new method is robust to
      counterfeiting, even when the malicious attackers are fully aware of the
      watermark embedding algorithm. It is shown that the presented new method can
      securely embed a message bit stream, such as personal signatures or copyright
      logos, into a host image as fragile watermarks. Compared with conventional
      fragile watermark techniques, this new statistical model based method modifies
      only a small amount of image data such that the distortion on the host image is
      imperceptible. Meanwhile, with the embedded message bits spreading over the
      entire image area through the statistical model, the new method can detect and
      localize image tampering. Besides, the new multiscale implementation of fragile
      watermarks based on the presented method can help distinguish some normal image
      operations such as JPEG compression from malicious image attacks and, thus, can
      be used for semi-fragile watermarking.

PMID- 17022281
TI  - B-spline image model for energy minimization-based optical flow estimation.
AB  - Robust estimation of the optical flow is addressed through a multiresolution
      energy minimization. It involves repeated evaluation of spatial and temporal
      gradients of image intensity which rely usually on bilinear interpolation and
      image filtering. We propose to base both computations on a single pyramidal cubic
      B-spline model of image intensity. We show empirically improvements in
      convergence speed and estimation error and validate the resulting algorithm on
      real test sequences.

PMID- 17022282
TI  - Minimal stochastic complexity image partitioning with unknown noise model.
AB  - We present a generalization of a new statistical technique of image partitioning
      into homogeneous regions to cases where the family of the probability laws of the
      gray-level fluctuations is a priori unknown. For that purpose, the probability
      laws are described with step functions whose parameters are estimated. This
      approach is based on a polygonal grid which can have an arbitrary topology and
      whose number of regions and regularity of its boundaries are obtained by
      minimizing the stochastic complexity of the image. We demonstrate that efficient
      homogeneous image partitioning can be obtained when no parametric model of the
      probability laws of the gray levels is used and that this approach leads to a
      criterion without parameter to be tuned by the user. The efficiency of this
      technique is compared to a statistical parametric technique on a synthetic image
      and is compared to a standard unsupervised segmentation method on real optical
      images.

PMID- 17022283
TI  - Level set segmentation with multiple regions.
AB  - The popularity of level sets for segmentation is mainly based on the sound and
      convenient treatment of regions and their boundaries. Unfortunately, this
      convenience is so far not known from level set methods when applied to images
      with more than two regions. This communication introduces a comparatively simple
      way how to extend active contours to multiple regions keeping the familiar
      quality of the two-phase case. We further suggest a strategy to determine the
      optimum number of regions as well as initializations for the contours.

PMID- 17022285
TI  - On the number of rectangular tilings.
AB  - Adaptive multiscale representations via quadtree splitting and two-dimensional (2
      D) wavelet packets, which amount to space and frequency decompositions,
      respectively, are powerful concepts that have been widely used in applications.
      These schemes are direct extensions of their one-dimensional counterparts, in
      particular, by coupling of the two dimensions and restricting to only one
      possible further partition of each block into four subblocks. In this paper, we
      consider more flexible schemes that exploit more variations of multidimensional
      data structure. In the meantime, we restrict to tree-based decompositions that
      are amenable to fast algorithms and have low indexing cost. Examples of these
      decomposition schemes are anisotropic wavelet packets, dyadic rectangular
      tilings, separate dimension decompositions, and general rectangular tilings. We
      compute the numbers of possible decompositions for each of these schemes. We also
      give bounds for some of these numbers. These results show that the new
      rectangular tiling schemes lead to much larger sets of 2-D space and frequency
      decompositions than the commonly-used quadtree-based schemes, therefore bearing
      the potential to obtain better representation for a given image.

PMID- 17022284
TI  - A technique for producing scalable color-quantized images with error diffusion.
AB  - To reliably and efficiently deliver media information to diverse clients over
      heterogeneous networks, the media involved must be scalable. In this paper, a
      color quantization algorithm for generating scalable color-indexed images is
      proposed based on a multiscale error diffusion framework. Images of lower
      resolutions are embedded in the outputs such that a simple down-sampling process
      can extract images of any desirable resolutions. Images possessing this scalable
      property support transmission over the Internet which contains clients with
      different display resolutions, systems with different caching resources and
      networks with varying bandwidths and QoS capabilities. Unlike most of the color
      halftoning algorithms available nowadays, the proposed algorithm is not dedicated
      for printing applications but for color-indexed displays. It works with any
      arbitrary palettes of different size.

PMID- 17022286
TI  - Background adjustment and saturation enhancement in ancient Chinese paintings.
AB  - This work presents a color enhancement scheme to virtually restore ancient
      Chinese paintings in electronic form. Two degradations result in color contrast
      loss in ancient Chinese paintings: paper aging and pigment fading. The proposed
      enhancement scheme comprises two subsequent methods: background adjustment and
      saturation enhancement. The former method, based on the Von Kries color
      conversion in the CIE xyY color space, retrieves the original color of the paint
      paper by modifying colors based on their similarity to the background color. The
      proposed saturation enhancement method makes colors more vivid and bright, and
      also improves the image contrast.

PMID- 17022287
TI  - Are billing disputes reported to the National Practitioner Data Bank?

PMID- 17022288
TI  - News about the minimum wage and its impact.

PMID- 17022289
TI  - Are you having fun at work?

PMID- 17022290
TI  - Diabetes on the rise; one-third don't know they have it.

PMID- 17022291
TI  - Lousy collections can cost you a bundle!

PMID- 17022292
TI  - An ethical imperative.

PMID- 17022293
TI  - Another option.

PMID- 17022294
TI  - Advances, understanding help alleviate fear.

PMID- 17022295
TI  - Use of osseointegrated implants in the restoration of head and neck defects.
AB  - Osseointegrated implants can be applied to facilitate retention, stability, and
      support for facial and intraoral prostheses used to restore head and neck
      defects. At the University of California, Los Angeles, Maxillofacial Prosthetics
      Clinic, retrospective studies have indicated that in nonirradiated maxillectomy
      patients, implant survival rates are 82.6 percent. In mandibles reconstructed
      with fibula free flaps, survival rates are 94.6 percent. Similarly, high implant
      survival rates have been observed for most sites used to support facial
      prostheses. Cumulative six-year survival rates for auricular sites exceed 95
      percent and for floor of nose sites, success rates exceed 87 percent. However,
      survival rates are low (53 percent) for implants placed in the frontal bone for
      retention of orbital prostheses and even lower for irradiated bone sites ranging
      from 63 percent in the maxilla to 27 percent in the orbit.

PMID- 17022296
TI  - Using implants for the growing child.
AB  - The use of implants for the growing child is not routinely recommended. The
      concerns about placing implants for patients in this age group are related to jaw
      growth. However, not all children with missing teeth need to wait for growth to
      be completed prior to implant placement. In this paper, the authors will discuss
      the indications for implant placement in the growing child. The decision for
      implant placement is based not only on growth, but also the number and location
      of the missing teeth.

PMID- 17022297
TI  - Prosthodontic treatment of patients with hypodontia.
AB  - Hypodontia is a relatively rare occurrence that can have a significant impact on
      treatment planning for those patients with the condition. This paper will
      describe the forms of hypodontia, as well as associated dental issues. Treatment
      planning considerations for children, adolescents, and adults will be presented.

PMID- 17022298
TI  - Dental management of chemoradiation patients.
AB  - The utilization of combined chemoradiation therapy has recently increased in the
      treatment of head and neck cancers. This patient population is significantly more
      prone to various oral complications during and after medical therapy. Oral
      complications and long-term effects include mucositis, xerostomia, alterations in
      taste, vascular compromise, mucosal thinning and increased risk of rampant caries
      and periodontal disease. The most serious oral complication that can arise is
      osteoradionecrosis. Managing patients properly prior to medical treatment can
      help decrease these potential complications during and after treatment. This
      purpose of this article is to review the different radiation and chemotherapy
      regimens used to treat patients with head and neck cancers, as well as protocols
      in the dental management of these patients before, during, and after medical
      treatment.

PMID- 17022299
TI  - Intensity-modulated radiation therapy and xerostomia.
AB  - Conformal radiation with intensity-modulated radiation therapy, IMRT, is a
      radiation technique that potentially can minimize the dose to salivary glands and
      thereby decrease the incidence of xerostomia. Precise target determination and
      delineation is most important when using salivary gland-sparing techniques of
      IMRT. The reduction of xerostomia may be achieved by sparing the salivary glands
      on the noninvolved oral cavity and keeping the mean parotid gland dose of < 26-30
      Gy if the treatment of disease is not compromised and parotid function
      preservation is desired.

PMID- 17022300
TI  - The her-story of toothpaste.

PMID- 17022301
TI  - [Neutrophil participation in early control and immune activation during
      experimental pulmonary tuberculosis].
AB  - BACKGROUND: Macrophages and neutrophils are professional phagocytes that
      participate in the control of mycobacterial infection. OBJECTIVE: We compared the
      pro-inflammatory cytokine production of both cell types during early pulmonary
      tuberculosis. MATERIAL AND METHODS: Balb/c mice were infected by intratracheal
      route with the H37Rv virulent strain, and bronchial washing cells were studied by
      cytofluorometry. RESULTS: A higher number of neutrophils with immunoreactivity
      against interleukin 1, interleukin 8 and tumor necrosis factor alpha were
      observed during the first week of infection. After, macrophages were the
      predominant cell type. In a second part of the study, infected mice were treated
      with the RB6-8C5 anti-neutrophil monoclonal antibody, and the course of the
      infection was observed. In comparison with controls, neutropenic mice showed
      higher bacillary loads in lungs and spleen, lower inflammatory infiltrate,
      smaller granulomas and lesser cutaneous delayed type hypersensitivity.
      CONCLUSIONS: These results show that neutrophils are the most abundant
      inflammatory cell type during early murine pulmonary tuberculosis, and they
      participate in the lung bacilli clearance and prevention of blood dissemination.
      Neutrophils are also an important source of proinflammatory cytokines,
      contributing to the early recruitment and activation of macrophages and
      lymphocytes, favoring cell mediated immunity against mycobacterial infection.

PMID- 17022302
TI  - [Predisposing risk factors that participate in neonatal sepsis mortality rate].
AB  - BACKGROUND: Neonatal sepsis is a frequent diagnosis in neonatal intensive care
      units and has been associated with a high mortality rate. OBJECTIVE: To determine
      the possible association between various risk factors and neonatal sepsis
      mortality rate. DESIGN: Cohort case control. MATERIAL AND METHODS: Two hundred
      medical records of newborns discharged from a neonatology unit, from January 1998
      to June 2002, with a neonatal sepsis diagnosis were reviewed. RESULTS: There was
      significance in birth weight of 1000 g or less, vein dissection for insertion of
      central venous catheter, gestational age of 30 weeks or less, and presence of
      mechanical ventilatory assistance (p < 0.01). Total parenteral nutrition also
      reached significance but as protective factor (OR: 0.15, CI 95% 0.07 - 0.31) (p <
      0.001). The multivariate analysis displayed similar results, except birth weight
      (p < 0.01). CONCLUSIONS: The above mentioned risk factors should be prevented in
      as much as possible. A factor to prevent mortality is total parenteral nutrition
      which should be always employed in cases where this is feasible.

PMID- 17022303
TI  - [Experience with the use of positron emission tomography (PET) in Mexico].
AB  - BACKGROUND: Positron Emission Tomography (PET) is a non-invasive imaging
      diagnostic tool that allows the study of specific biochemical processes using
      labeled molecules that closely mimic endogenous molecules. The two
      radiopharmaceuticals used in our facility are 13N-Ammonia and 18F-2-deoxy-2 fluor
      D-glucose (18F-FDG). 18F-FDG is the most common radiopharmaceutical used both at
      our Unit as well as worldwide, as it allows the study of tumor activity, the
      heart's metabolic activity, distinguish viable from non-viable myocardium and
      assess cerebral metabolism, among others. OBJECTIVES: Describe the experience in
      the use of PET scan in our country in the fields of oncology, cardiology and
      neuropsychiatry. METHODS: We performed an observational, retrospective, cross
      sectional, and descriptive study. RESULTS: We analyzed a total of 1,154 studies
      performed at the UNAM-PET-Cyclotron Unit belonging to the Faculty of Medicine at
      the National Autonomous University of Mexico (UNAM). From the studies, 72.1%
      (832) corresponded to oncology, whereas 18.5% (213) and 9.4% (109) belonged to
      cardiology and neuropsychiatry, respectively. CONCLUSIONS: The studies performed
      at the UNAM-PET-Cyclotron Unit places it as the site with the largest PET
      experience in our country.

PMID- 17022304
TI  - [Frequency of the metabolic syndrome among overweight and obese patients in a
      primary health care facility in northern Mexico].
AB  - OBJECTIVE: Assess the frequency of the metabolic syndrome (MS) among overweight
      and obese subjects attending a primary health care clinic in Tijuana, Baja
      California, Mexico. METHODS: Male and female patients over 20 years of age
      attending a primary health care setting during April-Sept 2004 were selected to
      participate in the study. Metabolic syndrome was defined using the Adult
      Treatment Panel III criteria (NCEP III). RESULTS: Three-hundred twenty one
      patients with a mean age 47.9 years were assessed. The MS frequency was 44% for
      those patients without previous history of diabetes mellitus or hypertension (n =
      281). The MS was present in 30% and 53% of overweight and obese patients
      respectively. Being an older male who had not been born in Baja California State
      were significantly associated with the presence of MS. CONCLUSIONS: The frequency
      of MS in a selected group of patients was common and higher than the national
      prevalence. The high frequency of MS in our study could be associated with a high
      prevalence of diabetes and obesity in the northwest population of Mexico.

PMID- 17022305
TI  - [Knowledge and perceptions of glaucoma among adults living in an urban area].
AB  - OBJECTIVE: To assess knowledge and opinions on glaucoma among subjects screened
      in a campaign for ocular disease detection in western Mexico. METHODS: Cross
      sectional, comparative and descriptive study. During a two-week period, adults of
      at least 40 years of age underwent a comprehensive ophthalmic examination. A
      questionnaire containing general and demographic data, as well as a set of
      questions related to both general and ocular health status were administered to
      all participants; specific questions assessing the level of knowledge and
      awareness on glaucoma were also included. A comprehensive battery of functional
      and structural tests was administered. Comparisons among subgroups according to
      different demographic characteristics were carried out. RESULTS: 492 subjects
      were screened, 389 (79.1%) completed all tests; 166 participants (42.6%) reported
      having completed grade school education; 174 subjects (44.7%) identified
      glaucoma, but 52 (29.9%) were unable to describe it correctly. Four (14.3%) out
      of 28 glaucomatous subjects were not able to correctly describe glaucoma.
      CONCLUSIONS: The level of knowledge and awareness of glaucoma is low among adults
      assessed in an urban region in western Mexico. Low levels of schooling among
      participants seem to have an impact on glaucoma knowledge and awareness.

PMID- 17022306
TI  - [Strengths and weaknesses of home management of diarrhea].
AB  - OBJECTIVE: The aim of the study was to analyze mothers home practices among
      children with acute diarrhea. METHODS: A cross sectional study was carried out in
      a group of 260 mothers of children with diarrhea. Mothers were requested to
      answer the "verbal biopsy" questionnaire to assess their practices concerning
      effective diarrhea management at home according to the World Health Organization
      and corresponding to the Norma Oficial Mexicana recommendations. Descriptive
      statistics and Chi square for differences were used. RESULTS: Two groups of
      mothers' were identified: those who had consulted a physician before attending
      the hospital (n = 191), and those who came to the hospital as their first choice
      (n = 69). The first group used antibiotics, antiemetics, breast-feeding and Oral
      Hydration Therapy more frequently than the second group (p < 0.05). CONCLUSIONS:
      The "verbal biopsy " instrument was useful to assess home management of children
      with diarrhea. This questionnaire was also useful to detect medical malpractice
      (unjustified prescription of antibiotics and antiemetics) as well as to identify
      best practices (continued breast feeding and oral hydration).

PMID- 17022307
TI  - [History of clinical studies on hypothalamic hormone analogs in Mexico].
AB  - Early clinical trials in Mexico with analogs of luteinizing hormone-releasing
      hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were
      reviewed. Extensive clinical studies were carried out at IMSS with agonists of LH
      RH, both in men and woman. All subjects responded to LH-RH agonists with a
      release of LH and FSH, but repeated administration of these analogs, initially
      aimed at stimulation of fertility (thought to stimulate fertility), was later
      shown to result in inhibition due to desensitization of pituitary gland and
      downregulation of LH-RH receptors. Various clinical investigations with LH-RH
      antagonists were also carried out. This included the first demonstration that LH
      RHantagonists can suppress LH and FSH and sex steroid secretion in men and women.
      Various studies in Mexico with early LH-RH antagonists aimed at the development
      of new contraceptive methods were reviewed. Modern LH-RH antagonist Cetrorelix
      was shown to be effective in men and women and useful in treatment of uterine
      leiomyomas and benign prostatic hyperplasia. Major oncological studies were also
      carried out with agonist D-Trp6-LH-RH and antagonist Cetrorelix in men with
      prostate cancer, which demonstrated therapeutic efficacy of both types of
      analogs. Some endocrine studies with early analogs of somatostatin were also
      cited and a clinical trial with somatostatin analog vapreotide in patients with
      relapsed prostate cancer was reviewed. All these studies played a major role in
      introducing analogs of hypothalamic-releasing hormones into clinical medicine.

PMID- 17022308
TI  - [Pharmacological treatment of acromegaly].
AB  - Acromegaly is an endocrine disorder usually due to a growth hormone (GH)
      secreting pituitary adenoma. This deforming disease is associated with several
      metabolic abnormalities and results in an elevated cardiovascular mortality.
      Pituitary transsesphenoidal surgery has been considered the treatment of choice,
      however, even in the most experienced hands this procedure succeeds in curing
      only 50 to 60% of the patients. Therefore, close to 50% of patients require an
      adjunctive form of treatment such as radiation therapy or the use of diverse
      medications that modulate GH secretion (somatostatin analogues) or action (GH
      receptor antagonists). The present review summarizes the clinical experience with
      these novel medications.

PMID- 17022309
TI  - [A fifty-six year old woman with painful nodules and skin ulcers].

PMID- 17022310
TI  - [Toxic epidermal necrolysis].
AB  - Toxic epidermal necrolysis is the prototype of a proapoptotic disease
      characterized by system CD95 dysrregulation. Drugs constitute the main antigenic
      triggers. Hystopatologically it is characterized by epidermis detachment and
      necrosis with apoptotic keratinocytes. Clinical presentation includes
      erithematous-ampullous lesions in the skin and mucous membranes. It is associated
      with serious complications such as severe sepsis and septic shock. The management
      in the intensive care unit includes support treatment and specific treatment with
      immunoglobulins that alter disease course. Recombinant activated Factor VII is
      effective to control the associated microvascular haemorraghe.

PMID- 17022311
TI  - [Case study of diffuse hemangiomatosis of the liver].
AB  - In adults, diffuse haemangiomatosis of the liver is a very rare condition. The
      aetiology and clinical evolution are not well understood, and the literature
      records isolated cases with different behaviours and treatments. Here we present
      the case of a 45-year-old patient with haemangiomatose lesions in both lobes of
      the liver, causing moderate to intense abdominal pain and a bloated sensation in
      the presence of an abdominal mass, but with hepatic and haematological functions
      remaining largely intact. Conventional ultrasound and CAT scan revealed diffuse
      lesions in both hepatic lobes, and this required the performance of a diagnostic
      laparoscopy to rule out hepatic metasteses or multiple liver abscess. As the
      findings consisted of large blue-black spongy masses involving both lobes of the
      liver, radical treatment of a resective type was not possible. After two years of
      follow-up, the patient still complains of diffuse abdominal pain of varying
      intensity, which is being treated with analgesics. Liver function tests have
      demonstrated a gradual increase in both liver enzymes and alkaline phosphatase,
      but without frank clinical evidence of clinical liver insufficiency.

PMID- 17022312
TI  - [Donato G Alarcon, founder of institutions devoted to respiratory diseases in
      Mexico].
AB  - Dr. Donato G. Alarcon was the founder director of the National Institute of
      Respiratory Diseases recently named "Ismael Cosio Villegas ", officially
      established on December 31, 1935. He was also the first president of the Mexican
      Society of Tuberculosis Studies, and the first director of its journal: the
      Mexican Journal of Tuberculosis and Respiratory Diseases, both starting in 1939
      and the first general director of the National Committee of Fight Against
      Tuberculosis. In Mexico only Dr. Donato G. Alarcon, in the respiratory diseases,
      and Dr. Ignacio Chavez, in the cardiovascular diseases, took the initial
      responsability of the three equivalent institutions: the National Institute, the
      Society of Specialists and the journal of the specialty. He was also the first
      pulmonologist elected director of the National Academy of Medicine of Mexico and
      director of the Faculty of Medicine of the National Autonomous University of
      Mexico.

PMID- 17022313
TI  - [Case study of a ruptured intracraneal dermoid tumor].

PMID- 17022314
TI  - [Recently sequenced human chromosomes].

PMID- 17022315
TI  - [Reflections on the board of occupational medicine in Mexico].
AB  - In January 2005, the National Normative Committee of Medical Specialties Boards
      withdrew their certification to the Mexican Board of Occupational Medicine. The
      Mexican Board of Occupational Medicine declared they did not need recognition
      from the National Normative Committee of Medical Specialties Boards and could
      operate independently. The implications of this state of affairs are critical in
      that they affect aspects beyond awarding diplomas and acknowledging professional
      competence in the fields of quality of medical attention, educational standards,
      law and ethics.

PMID- 17022316
TI  - [Factors participating in the variability of glycosylated hemoglobin levels].
AB  - Glycated hemoglobin values are a good indicator of metabolic control of the
      diabetic patients; however the levels can be influenced by analytic, clinic and
      biological variability. In the first, it is important to know that the variation
      coefficient between-laboratory should be < 3-4%; the second, depends on the
      metabolic control of the patients, while the third is determined by internal and
      external factors. Family studies had shown that genetic factors are involved in
      the biological variability of glycated hemoglobin. In order to have a correct
      interpretation of the glycated hemoglobin levels, it is important to know the
      causes of variability.

PMID- 17022317
TI  - Interview with Senator John Thune. Interview by Val J Halamandaris.

PMID- 17022318
TI  - Maximizing your investment: Recruitment and retention of speech-language
      pathologists in home care.

PMID- 17022319
TI  - Brand intergrity as a management strategy.

PMID- 17022320
TI  - Using process management to attack the cost quality paradox in home care.

PMID- 17022321
TI  - A marketing magic bullet?

PMID- 17022322
TI  - Technology meets private duty.

PMID- 17022323
TI  - Telehealth--A P4P tool for quality based reimbursement: its impact on quality
      care and customer service.

PMID- 17022324
TI  - Home health care nurses should follow case management standards to achieve
      patient outcomes.

PMID- 17022325
TI  - Managing urban speech therapy caseloads successfully by using telehealth.

PMID- 17022326
TI  - Home health care and hospice training is just a click away.

PMID- 17022327
TI  - Hospices and advance beneficiary notices.

PMID- 17022328
TI  - Technology makes good dollars and cents for home care: NAHC annual meeting can
      help prepare you.

PMID- 17022329
TI  - Passion, ethics and sales.

PMID- 17022330
TI  - Sittin' in the ritz.

PMID- 17022331
TI  - It's time for your mid-year checkup.

PMID- 17022332
TI  - Save money, improve quality, increase staff retention.

PMID- 17022333
TI  - Quick bites.

PMID- 17022335
TI  - Home care makes sense--dollars and cents.

PMID- 17022334
TI  - Apple pie and curry.

PMID- 17022336
TI  - The use of infant seating devices in child care centers.
AB  - OBJECTIVE: The purpose of this study was to compare the duration of time that
      infants in child care centers were placed in infant seating devices to the
      duration of time spent on the floor or being held by child care providers.
      METHOD: Thirty-eight infants who were typically developing (mean age = 4.5
      months) from eight child care centers were observed minute-by-minute for a
      consecutive 120 min, targeting the amount of time each infant spent in seating
      devices, on the floor, or being held by child care providers. RESULTS: The amount
      of time the infants spent in seating devices was significantly longer than on the
      floor (p= .0001) or being held by child care providers (p= .0001). CONCLUSION:
      All infants spent more time in seating devices than on the floor or being held by
      child care providers. Future research should explore seating device use in
      infants identified as at-risk or as having special needs, particularly how child
      care routines for these infants may influence seating device use, as well as the
      impact of this practice on these infants' motor development.

PMID- 17022337
TI  - Maternal attitudes and self-definition as related to perceptions of infant
      temperament.
AB  - Maternal childbearing attitudes and self-definition as related to maternal
      perceptions of infant temperament were investigated in a pilot study. Maternal
      attitudes, self-definition, and perceptions of infant temperament were determined
      through mothers' self-report. Results indicated that maternal attitudes-including
      self-confidence and feelings toward infants and children-were positively related
      to maternal perceptions of infant temperament. That is, mothers who reported low
      self-confidence and negative feelings toward infants and children in general also
      rated their infants' temperament as more negative. In addition, maternal work
      experience involving children was inversely related to maternal perceptions of
      infant temperament, in that those mothers who had more work experience with
      children rated their infants as being more difficult. The findings are consistent
      with Sameroff's transactional model of development (Sameroff & Chandler, 1975)
      wherein both the psychological and behavioral aspects of mother and infant create
      the milieu for further development.

PMID- 17022338
TI  - Integration and application of a home treatment program: a study of parents and
      occupational therapists.
AB  - The purpose of this article is to describe parental adherence to home treatment
      programs. A qualitative exploratory study with six parents and eight occupational
      therapists who used the brushing and compression technique (Wilbarger Protocol)
      was conducted. Participants were interviewed one or two times, exploring their
      experiences in adhering to the protocol. Data analysis focused on facilitators
      and hindrances to parental adherence and on occupational therapists' strategies
      used to encourage it. Parents identified their children's responses to brushing,
      its perceived efficacy, and interaction of the protocol with family daily
      schedules, as factors influencing their adherence. Occupational therapists
      identified only family daily schedules as influencing parental adherence. The
      findings are discussed in the context of the ecocultural theory of family
      accommodations.

PMID- 17022339
TI  - Critiquing the logic of the domain section of the Occupational therapy practice
      framework: domain and process.
AB  - The Occupational Therapy Practice Framework: Domain and Process (also known as
      the Framework), an official document of the American Occupational Therapy
      Association, advocates terminology and a classification system for concepts that
      are central to the profession of occupational therapy. Its use has been advocated
      in practice, research, education, and communications with those who wish to know
      more about occupational therapy. Given its importance to the profession and to
      society, the Framework deserves intense scrutiny and sustained scholarly inquiry.
      This article investigates the logic of Occupational Therapy Practice Framework:
      Domain and Process, with a focus on domain. Are definitions and classifications
      within the domain logically coherent? The Framework repeatedly violates two rules
      of logical definitions: (a) a unique term must be applicable to certain
      particulars and must not be applicable to others (the rule of precision); and (b)
      the particulars assigned to one term must not be assignable to another term
      unless there is a logical explanation (the rule of parsimony). The Framework also
      repeatedly violates two rules of logical classification: (a) a lower-level
      category must be classifiable only within its assigned higher-level category (the
      rule of exclusivity); and (b) all relevant particulars must be classifiable (the
      rule of exhaustiveness). The profession of occupational therapy needs one or more
      logically coherent conceptual frameworks, but the Framework is not recommended as
      a logical basis for practice, education, research, and external communications.
      Specific recommendations are made in support of the development of a logical
      framework and the refinement of existing frameworks.

PMID- 17022340
TI  - Searches and content of the OTseeker database: informing research priorities.
AB  - BACKGROUND: A strategic and prioritized approach to occupational therapy research
      is needed, particularly given the limited research funding available. Comparing
      occupational therapists' information needs with the research evidence available
      can potentially inform research debate within the profession. This study aimed to
      identify research topics most often sought by users of the OTseeker database and
      to compare these with the quantity of topics available in the database. METHOD: A
      random sample of keyword search terms submitted to OTseeker (n= 4,500) was coded
      according to diagnostic and intervention categories, and compared with the amount
      of research contained in OTseeker in 2004. RESULTS: Most frequently sought topics
      were relevant to the diagnostic categories of pediatric conditions (19%),
      neurology and neuromuscular disorders (17%), and mental health (17%). Most
      frequently sought intervention topics included modes of service delivery, sensory
      interventions, and physical modalities. Although many frequently sought topics
      had a correspondingly high volume of research in OTseeker, a few areas had very
      little content (e.g., fine motor skill acquisition, autistic spectrum disorder).
      This information is offered to inform discussions about research priorities and
      resource allocation for research within occupational therapy.

PMID- 17022341
TI  - A phenomenological study exploring the meaning of a seminar on spirituality for
      occupational therapy students.
AB  - There are many unanswered questions about the concept of spirituality and its
      relationship to occupational performance. The role of occupational therapists in
      addressing clients' spiritual needs is unclear, and the inclusion of spirituality
      as a topic in the educational curricula of occupational therapy students requires
      further attention. Focus groups and surveys were used in this phenomenological
      study to explore the lived experiences of 11 occupational therapy students
      participating in a 3-month graduate seminar entitled "Spirituality in
      Occupational Therapy Practice." The study was designed to help occupational
      therapy faculty better understand how students experience the relationship
      between occupational therapy and spirituality, and how educational programs can
      better prepare students to translate theoretical frameworks into practice.
      Findings explored the students' evolving belief systems, and began to reveal a
      diversity of beliefs and practices in the occupational therapy community related
      to spirituality. Implications for theory and practice are offered.

PMID- 17022342
TI  - National status of the entry-level doctorate in occupational therapy (OTD).
AB  - A multifaceted survey was conducted to identify the factors that academic
      occupational therapy (OT) programs were considering in making decisions as to
      whether the entry-level clinical doctorate (OTD) is a viable alternative for
      their institutions. The survey was sent in the summer of 2004 to program
      directors of all (150) occupational therapy programs in the United States.
      Responses were received from 111 programs (response rate of 74%). Quantitative
      (demographic) and qualitative (factor identification) data were compiled and
      analyzed. Supporting factors for the development of entry-level OTD programs
      included (a) coexistence of physical therapy doctorate program, (b) enhanced
      preparation of graduates, and (c) improved student recruitment. Impeding factors
      included (a) limited resources, (b) philosophical objections, and (c) lack of
      demand. In addition, results suggested that overall there is greater support for
      the OTD as a postprofessional degree. The study provided a historical record of
      current decision making in occupational therapy academic programs. In addition,
      the results of the study suggest a need for the development of national consensus
      regarding the place of the OTD in occupational therapy education.

PMID- 17022343
TI  - Beyond active learning: a case study of teaching practices in an occupation
      centered curriculum.
AB  - Although occupation-centered curricula are highly promoted, the teaching
      processes that convey such designs remain unclear. This case study elucidated
      occupation-centered teaching practices. Interview and observational data were
      collected over 8 weeks, and analysis involved coding transcriptions, data
      matrices, concept maps, journaling, and writing. Participants augmented active
      learning strategies with strategies that linked course topics to the subject of
      occupation. The use of linking strategies suggested that: (a) course content was
      treated as two-tiered; (b) neither content nor instructional processes were
      inherently occupation-centered; and (c) subject-centered education strengthens
      social learning theories. Although curricula may appear occupation-centered based
      on a curriculum description and course content, ultimately "linking
      opportunities" in the classroom constitute an essential feature that demarcates a
      program as occupation-centered.

PMID- 17022344
TI  - Outcomes of selected cases from the American Occupational Therapy Foundation's
      curriculum mentoring project.
AB  - This study investigated the outcomes of a yearlong formal curriculum-mentoring
      project sponsored by the American Occupational Therapy Foundation. Five
      occupational therapy faculty groups were selected through a competitive
      application process and paired with mentors to assist in curriculum change. The
      experiences of each of the teams were studied using multiple methods of data
      collection, including semistructured interviews conducted in person and via
      telephone, a mailed questionnaire, and bimonthly electronic journal entries. The
      process and outcomes of two representative cases are reported in this
      qualitative, critical case study analysis. Overall, the faculty groups in each of
      the two teams seemed to benefit from mentoring in differing degrees as a result
      of their participation in this curriculum mentoring project. An important finding
      was that a well-focused mentoring plan with clearly outlined expectations needs
      to be established at the onset of any formal mentoring project. Additionally, a
      systematic, strategic plan agreed on by both mentors and participants, with a
      clear outline of responsibilities, will enhance the outcomes of a mentoring
      relationship.

PMID- 17022345
TI  - Personal preference and quality of reach in healthy adult women.
AB  - OBJECTIVE: A common practice in occupational therapy is to have clients choose an
      object that they prefer to be used during treatment. This practice assumes that a
      preference for chosen items will hold greater meaning and result in higher
      quality of movement. Little research has been conducted that specifically
      addresses the effect that preference has on quality of movement. Therefore, the
      purpose of this study was to contribute to the knowledge by determining whether
      preference affects quality of movement. METHOD: Forty-three healthy right-hand
      dominant adult women between the ages of 18 and 60 years in Northwest Ohio
      engaged in this study. Each participant rank-ordered 15 magazines from most
      preferred to least preferred. The participant then reached for her most
      preferred, neutrally preferred, and least preferred magazines. RESULTS: When
      participants reached for the neutrally preferred magazines, movement time was
      significantly slower and movement units were significantly greater (less smooth)
      than when they reached for a magazine perceived as being the least preferred (p <
      .017). No differences were found between the three conditions in terms of
      displacement, peak velocity, or percentage of time to peak velocity, nor between
      the most preferred and the other two preferences. CONCLUSION: This study has
      shown that preference may not be an influential factor when performing simple
      reaches for magazines. Although there was a difference between the neutrally
      preferred and least preferred conditions, the goal when reaching during the
      neutrally preferred condition may have been different (i.e., to glean more
      information from the magazine cover) than when reaching in the least preferred
      condition (e.g., to reach for and discard the magazine as quickly as possible).
      These results reflect the complexity involved in the formation of meaning, of
      which preference is a part. Further exploration of individual preferences as well
      as personal goal formation and their impact on success in occupations of daily
      living is needed.

PMID- 17022346
TI  - Occupational factors and characteristics of the social network in people with
      persistent mental illness.
AB  - Associations between occupational factors and characteristics of the social
      network in people with persistent mental illness were investigated. Participant
      groups (N= 103) representing three types of daily occupations--working or
      studying, visiting community-based activity centers, and having no regular daily
      occupation--were selected for the study. Participants were assessed regarding
      social interaction and on the occupational factors of time spent in productive
      occupations, activity level, satisfaction with daily occupations, and perceived
      occupational value. The groups based on daily occupation did not differ in social
      interaction. Associations were found mainly between the subjective estimations of
      occupation--satisfaction and perceived value--and characteristics of the social
      network. In conclusion, experiential aspects of occupation were more closely
      related to social interaction than actual circumstances, such as type of daily
      occupation or time spent in productive occupations. The results suggest that
      occupational therapists should focus their attention on the patient's
      participation in a supportive social network because it may be related to valued
      and satisfying occupations.

PMID- 17022347
TI  - Associate editor's note--seeking integration, seeking coherence.

PMID- 17022348
TI  - Professional identity and workplace integration.

PMID- 17022349
TI  - "If I can't have you, no one can": development of a Relational Entitlement and
      Proprietariness Scale (REPS).
AB  - Relational proprietariness and entitlement have been theoretically related to
      partner violence following the threat of relationship dissolution. To date,
      however, no measure has been employed to verify such accounts. A multistage item
      pool development and refinement strategy was employed, resulting in a 32-item
      measure with strong construct validity. An online survey administered to 279
      students resulted in an interpretable factor structure of sexual proprietariness
      and entitlement, consisting of social, behavioral, and information control, and a
      potential factor of face threat reactivity. These factors added unique variance
      to the prediction of instrumental and expressive aggression, were related to self
      esteem and attachment, and were not contaminated by social desirability.
      Recommendations for bolstering the face threat reactivity factor and future
      studies are suggested. This measure provides a new tool that contributes to the
      prediction of intimate partner violence.

PMID- 17022350
TI  - Intimate partner violence, women, and work: coping on the job.
AB  - Intimate partner violence is a significant health problem for women, with
      consequences extending to work as well as society at large. This article
      describes workplace interference tactics, how women cope with violence at work,
      and workplace supports for a sample of recently employed women with domestic
      violence orders (DVO; n = 518). Results indicate that violent partners used a
      wide range of work interference tactics, that women were more likely to tell
      someone at work about the victimization than they were to hide the information,
      and that coworkers and supervisors provided a range of supports to women who did
      disclose their situation. Implications for further research and practice are
      discussed.

PMID- 17022351
TI  - An examination of sheltered battered women's perpetration of stalking and other
      unwanted pursuit behaviors.
AB  - In the current study, sheltered battered women (n = 105) self-reported whether
      they had perpetrated stalking or other unwanted pursuit behaviors (e.g.,
      harassment, threat) during relationship separations from their abuser. Results
      indicated that sheltered battered women who admitted perpetrating stalking
      behavior (about 25% of the sample) had more self-blame, depression, and a greater
      tendency to leave the shelter within the first week (45%) than did battered women
      who did not report perpetrating stalking behaviors. The majority of battered
      women who reported perpetrating stalking behavior also reported being victimized
      by stalking behaviors (bidirectional stalking). Although these women reported
      similarly high levels of fear toward their abuser as did unidirectionally stalked
      women, bidirectionally stalking women were less likely to perceive that their
      abuser was using his violence to obtain control over them and were more depressed
      and self-blaming. Directions for future research, recommendations for shelter
      staff, and the potential treatment implications of these findings are discussed.

PMID- 17022352
TI  - Peer and family influences on adolescent anger expression and the acceptance of
      cross-gender aggression.
AB  - Past research has examined the relative impact of family and peers on adolescent
      behavior, but very little research has examined it in relation to youth dating
      violence. Eight hundred and sixty-five adolescents, primarily urban Latino youth,
      completed self-administered surveys at school. Multivariate analyses indicated
      that exposure to prior family violence was not significantly associated with
      adolescents' aggressive expression of anger or their acceptance of cross-gender
      aggression. However, current conflict--either family or peer--was associated with
      adolescent behavior and attitudes, with the exception that current peer conflict
      was not significantly associated with adolescents' acceptance of male on female
      aggression. Parental monitoring and attachment were not found to be moderators of
      these relationships. Implications for dating violence interventions and future
      directions for research are explored.

PMID- 17022353
TI  - What do battered women want? Victims' opinions on prosecution.
AB  - Prosecutors have increasingly adopted mandatory prosecution in domestic violence
      criminal cases. There is little empirical evidence, however, that the policy is a
      good match for victims' needs. Interviews with 94 battered women, whose cases
      were randomly selected from prosecutors' files, focused on their opinions of
      prosecuting. A logistic regression explores the factors that predict whether
      victims favor or oppose prosecution. Open-ended responses are coded into themes
      using the goals of sentencing literature as a framework. Previous published works
      are also tentatively grouped into the same themes to look for trends in the
      field. The most frequent reason why victims oppose prosecution is that the crime
      is too minor to justify a penalty.

PMID- 17022354
TI  - Trends in the prevalence and characteristics of sexual violence: a cohort
      analysis.
AB  - Although recent statistics hint that rates of reported rape and child sexual
      abuse began to decline in the 1990s, little is known about changes in the
      characteristics of victimizations over time or about the implications of these
      changes for policy and services. This investigation uses data from a general
      population survey to examine sexual assault trends in two ways: by age cohort and
      by historical era in which a first sexual assault experience occurred. Findings
      suggest that the lifetime prevalence of sexual assault has not significantly
      changed across cohorts of women in their 20s to 50s. Characteristics of women's
      experiences across cohorts may be shifting, however, with early childhood
      experiences of sexual victimization showing a slight decline, accompanied by
      increases in assault rates during adolescence. Additionally, although help
      seeking among victims has increased, women's perceptions of their community's
      responsiveness have worsened slightly. Research and intervention implications are
      discussed.

PMID- 17022355
TI  - Factors associated with attitudes toward intimate partner violence: a study of
      women in Zambia.
AB  - Demographic, social, and empowerment factors associated with attitudes toward
      intimate partner violence (IPV) were investigated in a random sample of women (n
      = 5,029) aged 15-49 years in Zambia. Data was retrieved from the Zambia
      Demographic and Health Survey 2001-2002 (2003). The findings indicated
      demographic, social, and structural differences in attitudes toward IPV.
      Married/previously married and less educated women, employees in the agricultural
      sector, and women with a history of IPV were more likely to tolerate IPV. In
      addition, structurally disempowered women (i.e., women lacking access to
      information and autonomy in household decisions) were more likely to justify IPV
      than more-empowered peers. Most variables remained significant even when possible
      confounding was adjusted for using a logistic regression. The findings are
      discussed and implications for prevention as well as methodological issues
      considered.

PMID- 17022356
TI  - An integrated relapse prevention and relationship safety intervention for women
      on methadone: testing short-term effects on intimate partner violence and
      substance use.
AB  - This study tests the feasibility, safety, and short-term preliminary effects of a
      relapse prevention and relationship safety (RPRS) intervention in reducing drug
      use and the experience of intimate partner violence (IPV) among women on
      methadone. For this randomized controlled trial, 34 women who met IPV and drug
      use criteria were randomly assigned to either the RPRS condition (n = 16) or a
      one-session informational control (IC) condition (n = 18). RPRS participants were
      more likely than IC participants to report a decrease in minor physical or sexual
      IPV (OR = 7.1, p = .05), minor psychological IPV (OR = 5.3, p = .03) and severe
      psychological IPV (OR = 6.07, p = .03) at the 3-month follow-up. Data suggest
      that RPRS participants were also more likely than IC participants to report a
      decrease in any drug use at 3 months (OR = 3.3, p = .08). This study provides
      preliminary evidence that the RPRS intervention is effective in reducing IPV and
      drug use among women on methadone.

PMID- 17022357
TI  - ECG of the month. Repeated hospitalizations for dyspnea and edema. Dilated
      cardiomyopathy.

PMID- 17022358
TI  - Radiology case of the month Increasing elbow pain and swelling in a 14-year-old
      baseball pitcher. Medial humeral epicondylar avulsion fracture.

PMID- 17022359
TI  - Pathology case of the month. Thirty-year-old man with a right adrenal mass.
      Adrenocortical carcinoma with lung and right renal hilar metastases.

PMID- 17022360
TI  - Clinical case of the month. A 64-year-old man with postprandial epigastric pain.
      Chronic mesenteric ischemia.

PMID- 17022361
TI  - Splenic vein thrombosis presenting as Fusobacterium nucleatum bacteremia.

PMID- 17022362
TI  - Cutaneous manifestations due to Streptococcus pneumoniae bacteremia.

PMID- 17022363
TI  - Disseminated actinomycosis with multifocal muscular involvement.
AB  - We present a case of thoracic actinomycosis with hematogenous spread to the
      contralateral para-spinal muscles and ipsilateral lower extremity causing
      extensive myositis of the thigh. Aspiration secondary to chronic alcoholism and
      poor dentition were responsible for thoracic actinomycosis with subsequent
      hematogenous dissemination.

PMID- 17022364
TI  - PET imaging today: contribution to the initial staging and prognosis of patients
      with non-Hodgkin's lymphomas.
AB  - Malignant non-Hodgkin lymphomas (NHLs) are commonly staged according to the Ann
      Arbor staging system developed for Hodgkin's lymphoma. Recently, new staging
      modalities including metabolic imaging by positron emission tomography (PET)
      using F-18 fluorodeoxy-glucose (FDG) have been developed. In the present study,
      we investigated 77 untreated patients with different histologies of NHL both with
      conventional imaging techniques and FDG-PET. The patients were classified
      according to the World Health Organization classification and came from 2 major
      PET imaging centers in Louisiana and Texas. Seventy-six of 77 cases of NHLs were
      positive by PET imaging. PET imaging resulted, both in high/intermediate grade
      and indolent NHLs, in a higher stage in more than 20% of cases. In the subtype of
      high grade NHL diffuse large B cell lymphoma, upstaging by PET appears to be
      clinically relevant as a marker for a more aggressive tumor. In low grade NHL,
      stage changes were less pronounced. PET imaging did not reliably detect all cases
      of bone marrow involvement (especially in indolent lymphomas). However, even in
      low-grade NHL, clear indications exist for performing PET imaging. The value, the
      clinical relevance, and new developments in PET imaging for the different types
      of NHLs are discussed in detail.

PMID- 17022365
TI  - In vivo comparison of the efficacy of DIAGNOdent by visual inspection and
      radiographic diagnostic techniques in the diagnosis of occlusal caries.
AB  - OBJECTIVE: The purpose of this study was to compare in vivo the efficacy of
      DIAGNOdent measurements in the diagnosis of occlusal caries with conventional
      diagnostic methods (visual inspection and radiographic methods). METHODOLOGY: A
      total of 187 molar teeth in 161 individuals (87 female, 74 male) between the ages
      of 18 and 25, who were admitted to the Ondokuz Mayis University Faculty of
      Dentistry, Department of Restorative Dentistry, were included in this study. The
      study was evaluated by Ondokuz Mayis University Faculty of Medicine Ethical
      Committee and approved as ethically applicable. In the diagnostic phase of the
      study, all subjects' teeth were evaluated by two observers sequentially by visual
      inspection, radiography, and using DIAGNOdent. Carious lesions on the occlusal
      surfaces of molar teeth, which were evaluated by visual inspection, radiography
      and DIAGNOdent, were removed by using rotational cutting devices. Resulting
      cavities following caries removal were visually evaluated, and the level of
      caries was determined. RESULTS: Statistically significant differences were found
      when the visual inspection results, radiographic evaluation results, and
      DIAGNOdent evaluation results of two observers were compared for cavity depths.
      CONCLUSION: Although DIAGNOdent is an important diagnostic device, particularly
      for diagnosing hidden carious lesions in the dentine layer, it should be used
      along with visual examination in clinical practice, as DIAGNOdent is not superior
      to visual examination in detecting early stages of carious lesions.

PMID- 17022366
TI  - Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal
      examinations.
AB  - OBJECTIVE: The purpose of this study was to describe the utility of oral
      chemiluminescent lighting (FDA-cleared ViziLite) as an adjunct to standard visual
      examination (SVE) to enhance visualization of mucosal lesions, particularly those
      "clinically suspicious" for oral pre-cancer or cancer. Subjects were considered
      at risk for oral cancer or pre-cancer if they have no a priori knowledge of the
      presence or absence of an oral lesion at the time of examination. METHODOLOGY:
      Five-hundred and one consecutive consenting subjects, over 40 years of age and
      with a positive tobacco history, received a standard visual examination with
      conventional incandescent lighting, followed by chemiluminescent lighting. All
      lesions were recorded, and for lesions detected by both screening modalities,
      comparisons were made of the subjective parameters of lesion brightness,
      sharpness, surface texture, and relative size. RESULTS: A total of 410 epithelial
      lesions were detected in 270 subjects by standard visual examination, of which
      127 were clinically "suspicious" for oral cancer and pre-cancer. Ninety-eight
      lesions were also visualized by chemiluminescent lighting as "aceto-white" (CL+),
      in addition to six lesions not previously seen by standard visual examination.
      Seventy-seven of the CL+ lesions (78.5%) were clinically suspicious; all
      "suspicious" lesions with an ulcerative component and ulcerated lesions
      consistent with trauma were CL+. Leukoplakias were significantly more likely to
      be CL+ than erythroplakias (p < 0.01). Overall, those lesions illuminated by
      chemiluminescent lighting appeared brighter, sharper, and smaller compared to
      incandescent illumination. CONCLUSION: The results of this study suggest that
      oral chemiluminescent lighting, when used as a screening adjunct following the
      standard visual oral examination, provides additional visual information.
      Leukoplakias may be more readily visualized by chemiluminescence. Studies are
      underway to explore the clinical significance and predictive value of oral
      chemiluminescent lighting.

PMID- 17022367
TI  - Sealing ability of a new experimental "cold ceramic" material compared to glass
      ionomer.
AB  - OBJECTIVE: The purpose of this study was to compare the sealing ability of a new
      experimental material named "cold ceramic" with glass ionomer using an
      electrochemical method. METHODOLOGY: Forty extracted human teeth were used in
      this study. The crowns were removed at the cemento-enamel junction. The roots
      were prepared, the apical 3 to 4 mm of each root was resected, and a class 1
      cavity of 2 mm depth was prepared. After application of nail polish to the
      external surface of the roots, the samples were randomly divided into two groups,
      each with 20 roots. Each sample was filled with one of the two materials. After
      24 hours, to allow complete setting, the roots were immersed in normal saline
      solution for 10 days. Microleakage was measured by an electrochemical method.
      RESULTS: The results indicated that there is a statistically significant
      difference in the microleakage between the two materials (p = 0.0001), with the
      cold ceramic providing a better seal than the glass ionomer. CONCLUSION: Cold
      ceramic has proper sealing ability and reduced initial setting time that
      demonstrate its potential as a root end filling material.

PMID- 17022368
TI  - Clinical and microbiological effects of subgingival irrigation with Streblus
      asper leaf extract in chronic periodontitis.
AB  - OBJECTIVE: To determine the clinical and microbiological effects of subgingival
      irrigation of Streblus asper leaf extract (SAE) solution as an adjunct to scaling
      and root planing (SRP) in chronic periodontitis patients. METHODOLOGY: Forty-two
      subjects were included and treated with SRP at baseline (week 0), followed by
      subgingival irrigation with saline (control group, n=21) or SAE (test group,
      n=21) solution (80 mg/ml) at weeks zero, one, two, three, and four. Clinical
      parameters, including gingival index (GI), plaque index (PI), probing depth (PD),
      and relative attachment level (RAL) were measured at weeks zero, six, and 12.
      Microbiological parameters were measured at weeks zero, one, two, three, four,
      six, and 12. RESULTS: The SAE solution significantly reduced the GI compared with
      saline solution (p < 0.01). However, a reduction in PI, PD, and RAL was noted for
      both groups, with no statistically significant intergroup differences. The
      reduction in the number ofA. actinomycetemcomitans and/or P. gingivalis was
      maintained throughout the study period after subgingival irrigation with SAE
      solution, while an initial reduction and subsequent rebound were observed after
      saline irrigation. However, the mean number and mean percentages of sites with 10
      times the reduction in number of these bacteria were not significantly different
      between the two groups. CONCLUSION: Subgingival irrigation with SAE solution as
      an adjunct to SRP is effective at reducing gingival inflammation, but not PD,
      RAL, and the number of A. actinomycetemcomitans and/or P. gingivalis.

PMID- 17022369
TI  - Effects of hydrogen peroxide bleaching strips on tooth surface color, surface
      microhardness, surface and subsurface ultrastructure, and microchemical (Raman
      spectroscopic) composition.
AB  - OBJECTIVE: This study examined the effects of hydrogen peroxide tooth bleaching
      strips on the surface hardness and morphology of enamel and the ultrastructure
      and chemical composition of enamel and dentin in vitro. METHODOLOGY: Sound human
      molars were ground and polished to prepare a uniform substrate for bleaching
      treatments. A cycling treatment methodology was employed which alternated ex vivo
      human salivary exposures with bleaching treatments under conditions of controlled
      temperature and durations of treatment. Bleaching treatments included commercial
      Crest Whitestrips bleaching strips, which utilize hydrogen peroxide in a gel as
      the in situ bleaching source at 6.0 and 6.5% concentrations of H2O2. Control
      treatments included an untreated group. Crest Whitestrips bleaching included
      treatment exposures simulating 2x the recommended clinical exposures (28 hours
      bleaching). Surface color measurements were taken prior to and following
      bleaching to ensure tooth bleaching activity. The effects of bleach on physical
      properties of enamel were assessed with microhardness measures. Ultrastructural
      effects were classified by surface and subsurface confocal laser scanning
      microscopy (CLSM) and scanning electron microscopy (SEM) techniques. In addition,
      the effects of bleaching on tooth microchemical composition was studied in
      different tooth regions by coincident assessment of Raman spectroscopic
      signature. RESULTS: Color assessments confirmed significant ex vivo tooth
      bleaching by Whitestrips. Surface microhardness and SEM measures revealed no
      deleterious effects on the enamel surfaces. CLSM micromorphological assessments
      supported the safety of hydrogen peroxide bleaching strips both on surface and
      subsurface enamel, DEJ, and dentin ultrastructure. Raman spectroscopy analysis
      demonstrated no obvious effects of bleaching treatments on the microchemical
      composition of enamel and dentin. CONCLUSION: These results confirm that tooth
      bleaching with hydrogen peroxide whitening strips does not produce changes in
      surface/subsurface histomorphology or in surface microhardness and ultrastructure
      of treated teeth. In addition, for the first time, these results confirm the
      safety of hydrogen peroxide bleaching strips to tooth microchemical composition
      as measured by Raman spectroscopy.

PMID- 17022370
TI  - Interproximal gingivitis and plaque reduction by four interdental products.
AB  - OBJECTIVE: The study was conducted to compare the performance of three
      interdental products to dental floss in the control and removal of plaque, and in
      the reduction of gingivitis. METHODOLOGY: One-hundred and twenty subjects were
      screened for the presence of interproximal sites of a size suitable for a GUMO Go
      Betweens cleaner, and for being in compliance with inclusion and exclusion
      criteria. They were then assessed with the Plaque, Gingivitis, and Eastman
      Interdental Bleeding Indices (EIBI) at baseline, given a prophylaxis, randomly
      assigned to one of four products (Glide dental floss, Butler flossers, GUM Go
      Betweens cleaners, and GUM Soft-Picks cleaners), and given product use
      instructions. Subjects returned at three weeks for a compliance review and at six
      weeks for a final visit. Plaque was assessed at the final visit before and after
      using the assigned products. Plaque, gingivitis, and bleeding scores were
      evaluated by analysis of covariance using the baseline measurements as the
      covariate. RESULTS: All four interdental products significantly reduced
      interdental plaque from baseline to before-use at the final visit (after six
      weeks) employing baseline plaque as a covariate. Reductions were 16% to 24%.
      Similarly, use of the products at the final visit resulted in 26% to 31%
      reductions in plaque with the before-use plaque as a covariate. Interdental
      gingivitis scores showed a reduction both lingually and buccally, with reductions
      ranging from 27% to 36% for the former and 34% to 53% for the latter (baseline
      was the covariate). No statistical differences were found between the products on
      the lingual interdental sites. The Go-Betweens cleaners showed a statistically
      greater reduction in the Gingival Index score buccally than the other three
      products. No differences were noted among the products for the EIBI. CONCLUSION:
      In this study, dental floss, the recognized "gold standard" for gingivitis
      reduction, was matched in performance by flossers and an interdental cleaner with
      small elastomeric fingers, and surpassed by an interdental brush. All products
      performed comparably for plaque reduction and removal.

PMID- 17022371
TI  - Mechanisms of telomerase binding to telomeres.
AB  - There are essentially two alternative mechanisms for the binding of telomerase to
      telomeres, assuming that a protective component is initially bound to the
      telomerase binding region on the telomeres. Either the protective (or blocking)
      agent first dissociates and telomerase binds thereafter, or telomerase binds
      first and the protective agent then dissociates from the ternary complex. In the
      limit, this second possibility permits the ternary complex to become a transition
      complex (creating another possible mechanism). Numerical simulation of both rapid
      mixing and chemical relaxation is used to study these alternatives. We aim to
      determine how the mechanisms may be distinguished experimentally and identify an
      appropriate experimental design. We show that rapid mixing experiments are better
      than chemical relaxation experiments, since the latter are more affected by the
      statistics of single molecule kinetics. However, hidden fast steps can only be
      revealed by chemical relaxation. The detection of mechanistic changes hinges on
      linking fluorescence reporters to the reaction components, either directly
      (chemically) or indirectly (via an indicator reaction). Fluorescence is excited
      by two-photon absorption in a small reaction volume. Various detection strategies
      and design issues are examined, including limitations imposed by diffusion.
      Constant rather than stopped flow is shown to be preferable.

PMID- 17022372
TI  - Effects of post low-dose X-ray irradiation on carbon tetrachloride-induced
      acatalasemic mice liver damage.
AB  - The catalase activities in the blood and organs of the acatalasemic (C3H/AnLCsb
      Csb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCSa-Csa)
      mouse. We examined the effects of post low-dose (0.5 Gy) X-ray irradiation which
      reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in
      acatalasemic or normal mice. As a result, the 0.5 Gy irradiation after carbon
      tetrachloride administration decreased the glutamic oxaloacetic and glutamic
      pyruvic transaminase activity in the acatalasemic mouse blood to a level similar
      to that of the acatalasemic mouse blood not treated with carbon tetrachloride;
      this is in contrast to a high-dose (15 Gy) irradiation. In the same manner,
      pathological disorder was improved by 0.5 Gy irradiation. The fat degeneration in
      normal mice was quickly reduced, in contrast to acatalasemic mice. These findings
      suggest that low-dose irradiation after carbon tetrachloride administration
      accelerates the rate of recovery and that catalase plays an important role in the
      recovery from hepatopathy induced by carbon tetrachloride, in contrast to high
      dose irradiation.

PMID- 17022373
TI  - Water and electrolyte changes in skeletal and cardiac muscles of rats during
      prolonged hypokinesia.
AB  - The objective of this study was to show that hypokinesia (diminished movement)
      could affect differently water and electrolyte content in muscles having minimum
      differences in their function and morphology. To this end, we studied water and
      electrolyte content in skeletal and cardiac muscles, fluid excretion, electrolyte
      absorption, and electrolyte levels in plasma, urine and feces of rats during
      prolonged hypokinesia (HK). Studies were conducted on one-hundred-twenty-six 13
      weeks old male Wister rats during a pre-hypokinetic period and a hypokinesia
      period. Animals were equally divided into two groups: vivarium control rats (VCR)
      and hypokinetic rats (HKR). Hypokinetic animals were kept in small individual
      cages which restricted their movements in all directions without hindering food
      and water intake. Control rats were housed in individual cages under vivarium
      control conditions. Sodium (Na+) and potassium (K+) absorption, electrolyte and
      water content in cardiac muscles (right and left ventricle), thigh extensor
      (quadriceps femoris muscle) and long muscle of the back (biceps femoris muscle),
      urine volume, and electrolyte levels in plasma and urine and feces did not change
      in VCR when compared to their pre-hypokinetic levels. The absorption of Na+ and
      K+, water and electrolyte content in cardiac and skeletal muscles decreased
      significantly, while urine volume, plasma electrolyte levels and urine and fecal
      electrolyte excretion increased significantly in HKR compared with their pre-HK
      values and with their respective vivarium control (VCR). Water and electrolyte
      content decreased more significantly in skeletal than in cardiac muscles. Water
      and electrolyte levels decreased more in the thigh extensor and in the right
      ventricle than in the long muscle of the back, the left ventricle or the septum.
      Muscles suffering from higher water and electrolyte loss against the background
      of lower water and electrolyte content show lower water and electrolyte
      deposition. Lower electrolyte and water content in skeletal than in cardiac
      muscle shows that water and electrolyte content decreases more in skeletal than
      cardiac muscles. Skeletal muscle showed lower water and electrolyte content than
      cardiac muscle indicating that the risk for decreased muscle water and
      electrolyte content is inversely related to the muscle function and morphology,
      i.e., the more weight-bearing supporting function and morphology muscles have,
      the higher the risk for lower muscle water and electrolyte content. It was
      concluded that the greater muscle function and morphology, the lower electrolyte
      and water deposition, the higher water and electrolyte losses, and the lower
      water and electrolyte content.

PMID- 17022374
TI  - What befalls the proteins and water in a living cell when the cell dies?
AB  - The solvency of solutes of varying molecular size in the intracellular water of
      freshly-killed Ehrlich carcinoma cells fits the same theoretical curve that
      describes the solvency of similar solutes in a 36% solution of native bovine
      hemoglobin--a protein found only in red blood cells and making up 97.3% of the
      red cell's total intracellular proteins. The merging of the two sets of data
      confirms the prediction of the AI Hypothesis that key intracellular protein(s) in
      dying cells undergo(es) a transition from: (1) one in which the polypeptide NHCO
      groups assume a fully-extended conformation with relatively strong power of
      polarizing and orienting the bulk-phase water in multilayers; to (2) one in which
      most of the polypeptide NHCO groups are engaged in alpha-helical and other
      "introvert" conformations (see below for definition) with much weaker power in
      polarizing-orienting multilayers of bulk-phase water. This concordance of the two
      sets of data also shows that what we now call native hemoglobin--supposedly
      denoting hemoglobin found in its natural state in living red blood cells--, in
      fact, more closely resembles the water-polarizing, and -orienting intracellular
      proteins in dead cells. Although in the dead Ehrlich carcinoma cells as well as
      in the 36% solution of native hemoglobin, much of the protein's polypeptide NHCO
      groups are engaged in alpha-helical and other "introvert" conformation (Perutz
      1969; Weissbluth 1974), both systems produce a weak but nonetheless pervasive and
      "long-range" water polarization and orientation. It is suggested that in both the
      dead Ehrlich carcinoma ascites cells and in the 36% native bovine hemoglobin
      solution, enough polypeptide NHCO groups assume the fully-extended conformation
      to produce the weak but far-reaching multilayer water polarization and
      orientation observed.

PMID- 17022375
TI  - Predictors of failure of endovascular therapy for peripheral arterial disease.
AB  - The objective of this study was to assess the usefulness of a comparison of
      clinical failure and restenosis rates of endovascular procedures at 1 year in
      patients with peripheral arterial disease. The resulting comparison is presented
      as "clinical failure/restenosis coordinate." The authors screened 171 papers
      describing the outcome of lower extremity angioplasty or stent placement. In 20
      of them, authors reported detailed outcomes of interest, including baseline
      demographic measurements, location of arterial occlusive lesions, a measure of
      restenosis (measured by ankle-brachial indices, ultrasonography, or angiography),
      and clinical outcomes (mortality, repeat percutaneous transluminal angioplasty,
      or amputation). An overview of these 20 angioplasty papers was performed. Besides
      the usual meta-analyses of each end point separately, data were also plotted as
      coordinates of clinical failure versus restenosis. The clinical failure-to
      restenosis coordinate was calculated and reported for percutaneous transluminal
      angioplasty of the aortoiliac and femoropopliteal distributions. Clinically
      reported outcomes in the literature were used to calculate the clinical
      failure/restenosis coordinate. This value was significantly different for various
      locations of the angioplasty and various baseline angiographic characteristics. A
      numeric coordinate pair of clinical failure and restenosis is identifiable in
      patients undergoing endovascular treatment of peripheral arterial disease. The
      varying coordinates may be important in elucidating the incidence and mechanisms
      of clinical failure after endovascular treatment. The coordinate reported in this
      article is hypothesis-generating about mechanisms of endovascular treatment
      failure. This coordinate is important in determining the role of restenosis in
      the clinical failure of endovascular therapy of peripheral arterial disease.

PMID- 17022376
TI  - Optimal duration of treatment in surgical patients with calf venous thrombosis
      involving one or more veins.
AB  - The aim of this study was to evaluate different durations of treatment in
      patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The
      authors studied 2 groups of patients with postsurgical CVT diagnosed by echo
      color Doppler. The first group consisted of 68 patients with CVT involving a
      single vein, and the second group consisted of 124 patients with CVT involving 2
      or more veins. Immediately after diagnosis, all patients were treated with
      nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5-6
      days of treatment, when the international normalized ratio (INR) was stabilized
      between 2 and 3. Each group was divided into 2 subgroups receiving
      anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was
      proximal extension of the thrombotic lesion, defined as the extension of the
      thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT
      there was no significant difference between the 2 subgroups, whereas in patients
      with CVT involving 2 or more vessels, a statistically significant difference was
      observed, the number of cases showing proximal extension of the thrombus being
      higher among patients treated for 6 weeks. Twelve weeks of anticoagulation
      treatment is better than 6 weeks only in patients with postsurgical CVT involving
      2 or more veins.

PMID- 17022377
TI  - The effect of walking with high-heeled shoes on the leg venous pressure.
AB  - It is common belief that the use of high-heeled shoes is deleterious to venous
      return, by impairing the efficiency of the muscular calf pump. Ambulatory venous
      pressure obtained with dorsal foot venipuncture is the gold standard in the
      evaluation of venous pressure during walking, but it is not routinely used in
      clinical practice. The objective of the present study was to determine the
      variations in leg venous pressure obtained with a new noninvasive method, in
      individuals without venous disease, walking without shoes and wearing high-heeled
      shoes. A new method of evaluation of the venous pressure by means of air
      plethysmography was applied to 10 volunteers (20 limbs). The patients were
      evaluated while standing, with orthostatic flexion and extension foot movements,
      and while walking on a treadmill barefooted and wearing high-heeled shoes. It was
      found that the variation on the cuff pressure during walking with high-heeled
      shoes was higher than the variation on the cuff pressure walking barefooted (52.2
      +/- 8.89 X 26.65 +/- 6.7 mm Hg, p < 0.0001), and the final hydrostatic venous
      pressure was lower (51.5 +/- 12.78 X 61.5 +/- 8.44 mm Hg). The use of high-heeled
      shoes increases muscular effort during walking and diminishes the leg venous
      pressure compared with barefooted.

PMID- 17022378
TI  - Improvement of diabetic microangiopathy with pycnogenol: A prospective,
      controlled study.
AB  - The aim of this study was to investigate the clinical efficacy of oral Pycnogenol
      (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy.
      Patients without a history of diabetic ulcerations were treated with Pycnogenol.
      Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of
      150 mg daily for 4 weeks). A group of 30 patients was included (severe
      microangiopathy); 30 comparable patients were observed as controls (no treatment
      during the observation period). All patients (age, 59 years; range, 55-68 years;
      male:female = 18:12) included in the treatment group completed the 4-week study.
      Also, all controls completed the follow-up period. There were no drop-outs. All
      included subjects had signs and symptoms of diabetic microangiopathy. The
      duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD
      = 3). After 4 weeks, microcirculatory and clinical evaluations showed a
      progressive decrease in skin flux at rest in the foot (indicating an improvement
      in the level of microangiopathy), a significant decrease in capillary filtration,
      and a significant improvement in the venoarteriolar response in all treated
      subjects. There were no visible effects in controls except a slight reduction in
      skin flux at rest in the foot. Treatment was well tolerated in both groups. In
      conclusion, this study confirms the clinical efficacy of Pycnogenol in patients
      with diabetic microangiopathy. The study indicates the clinical role of
      Pycnogenol in the management, treatment, and control of this common clinical
      problem. The treatment may be also useful to prevent diabetic ulcerations by
      controlling the level of microangiopathy.

PMID- 17022379
TI  - Cardiac function, inflammatory mediators and mortality in critical limb ischemia.
AB  - Patients with critical limb ischemia (CLI) have a high frequency of concomitant
      coronary heart disease and congestive heart failure. The aim of the study was to
      evaluate cardiac function in relation to inflammatory markers and 1-year
      mortality rate among patients with CLI. The authors investigated 232 consecutive
      patients with CLI by means of electrocardiogram (ECG), and measurements of
      endothelin (ET)-1, tumor necrosis factor alpha (TNF)alpha, interleukin (IL)-6,
      neopterin, CD40 ligand, and 8-epi-prostaglandin (PG)F2alpha in plasma.
      Echocardiography (echo) was performed in 88 (38%) patients. One-year mortality
      rate was assessed after prospective follow-up. One hundred and eighty-six (80%)
      patients had sinus rhythm (SR), 36 (16%) had atrial fibrillation or flutter (AF),
      and 10 (4%) pacemaker rhythm. Ischemic ECG changes occurred in 143 (62%)
      patients. Patients with AF showed higher IL-6 (p = 0.0296) and neopterin (p =
      0.0494) concentrations. Patients with ischemic ECG changes showed higher ET-1 (p
      = 0.0303), 8-epi-PGF2alpha (p = 0.0027), neopterin (p = 0.0004) concentrations
      and 1-year mortality rate (p = 0.0105). The difference in ET-1 remained in
      logistic regression (p = 0.0152). Internal diameter of the left ventricle on echo
      correlated with IL-6 (r = 0.345, p = 0.0017), TNFalpha (r = 0.240, p = 0.0273),
      and neopterin (r = 0.327, p = 0.0028). Internal diameter of the left atrium
      correlated with TNFalpha (r = 0.384, p = 0.0092) and neopterin (r = 0.526, p =
      0.0004), and ejection fraction (EF) correlated inversely with IL-6 (r = -0.380, p
      = 0.0015) and neopterin (r = -0.346, p = 0.0038). Patients with EF <40% showed
      higher (p = 0.0462) 1-year mortality rate than patients with EF >40%. In
      conclusion, in critical limb ischemia, cardiac rhythm disturbances and ischemic
      ECG changes were related to inflammatory mediators and predicted 1-year mortality
      rate. The inflammatory mediators correlated with echocardiographic signs of
      congestive heart failure.

PMID- 17022380
TI  - Cutting balloon angioplasty for the treatment of in-stent restenosis in
      diabetics: A matched comparison of 6 months' outcome with conventional balloon
      angioplasty.
AB  - Ranging from 24% to 55%, angiographic in-stent restenosis (ISR) rates in
      diabetics are higher than the 17% to 28% rates observed in nondiabetics. There
      are controversies regarding optimal treatment for ISR. Recently, cutting balloon
      angioplasty (CBA) emerged as a tool in management. The authors assessed the
      hypothesis that CBA has advantages over conventional percutaneous transluminal
      balloon angioplasty (PTCA) in treatment of ISR in diabetics. CBA or PTCA was
      applied to 165 diabetics (267 ISR lesions) in their institution. With a computer
      algorithm, an attempt was made to match each lesion in the CBA group with a
      corresponding lesion in the PTCA group. The lesion pairs should match with
      respect to the patients' age and gender, type of target vessel and stent,
      reference vessel diameter, and baseline minimal lumen diameter (MLD). Following
      the matching process, 55 ISR lesion pairs were identified. Baseline patient
      characteristics were similar among the groups (p = NS). There was no difference
      in the in-hospital major adverse cardiac events (MACE) between the groups,
      whereas MACE at follow up was significantly lower in the CBA group compared to
      the PTCA group (CBA, 20.0% vs PTCA, 43.6%, p<0.05). The recurrent ISR rate was
      significantly lower in the CBA group compared to the PTCA group (CBA, 27.3% vs
      PTCA, 49.1%; p < 0.05). Also, a diffuse pattern of recurrence was more common in
      lesions treated with PTCA, whereas a focal pattern of recurrence was more common
      in the CBA group. The minimal luminal diameter at follow-up, the acute gain, and
      net gain were significantly higher in the group of lesions treated with CBA than
      in the PTCA group. In addition, a significantly higher late loss and loss index
      at follow-up were observed in the PTCA group compared to the CBA group. CBA has
      advantages over PTCA in treatment of diabetic patients with ISR, with better
      immediate and follow-up angiographic outcomes, and better follow-up clinical
      outcome.

PMID- 17022381
TI  - Comparison of direct stenting versus conventional stent implantation on blood
      flow in patients with ST-segment elevation myocardial infarction.
AB  - As compared with balloon angioplasty, stent implantation in treatment of acute
      myocardial infarction (AMI) reduces abrupt vessel closure, restenosis, and
      reocclusion rate. However, a few studies have demonstrated the safety and
      feasibility of direct stenting compared to conventional stent implantation
      technique. This study was designed to compare possible advantages of direct
      stenting with conventional stent implantation on immediate coronary blood flow
      and short-term clinical benefits in patients with AMI. Fifty patients with AMI
      who underwent mechanical revascularization were eligible for the study. The
      patients were randomly assigned to undergo either direct stenting (n = 25) or
      conventional stent implantation (n = 25). Before and after the procedure
      thrombolysis in myocardial infarction (TIMI) flow and postprocedural corrected
      TIMI frame count (cTFC) of the infarct-related artery were measured. There was no
      difference in TIMI flow distribution at baseline between the 2 groups. TIMI 3
      flow rate significantly increased after procedure in both groups compared to
      baseline (p < 0.05). Postprocedural cTFC was found significantly lower in the
      direct stent arm compared to conventional stenting (p < 0.001). Both during and
      after the procedure the complication rate and procedural time were lower in the
      direct stenting arm. Direct stenting provides better immediate coronary blood
      flow and is a safe and feasible method compared with conventional stenting in
      patients with AMI. Improvement in coronary blood flow measured by the corrected
      TIMI frame count method may suggests a significant reduction of microvascular
      injury.

PMID- 17022382
TI  - Systemic versus coronary levels of inflammation in acute coronary syndromes.
AB  - To address a possible link between systemic and coronary inflammation in the
      setting of acute coronary syndromes, the authors examined both levels of 3
      inflammatory mediators such as high sensitive C-reactive protein (hs-CRP),
      interleukin (IL)-6, and matrix metalloproteinase (MMP)-9 in patients with the
      early phase of acute myocardial infarction (AMI). In total, 20 patients with AMI
      showing minimal elevation of cardiac enzymes were studied. Before angioplasty,
      peripheral blood and culprit coronary thrombus were sampled to compare systemic
      and coronary levels of hs-CRP, IL-6, and MMP-9. Relation of systemic levels of hs
      CRP and IL-6 to culprit coronary morphology was also evaluated by the use of
      intravascular ultrasound. Systemic and coronary levels of hs-CRP were nearly
      equivalent (4.3 +/- 5.0 vs 4.7 +/- 5.4 mg/L, p = 0.279), whereas IL-6 and MMP-9
      showed higher in coronary levels than in systemic levels (169 +/- 154 vs 93 +/-
      107 microg/mL, p = 0.002 and 164 +/- 116 vs 103 +/- 94 ng/mL, p = 0.018,
      respectively). Systemic levels of hs-CRP were correlated with coronary levels of
      IL-6 (r = 0.566, p = 0.009). Culprit coronary plaque area demonstrated a positive
      relation with systemic levels of hs-CRP (r = 0.466, p = 0.038) and also IL-6 (r =
      0.707, p <0.001). The present study may provide an important insight into the
      link between systemic and coronary levels of inflammation, which is also
      associated with vulnerable coronary morphology in the setting of acute coronary
      syndromes.

PMID- 17022383
TI  - Isolated and significant left main coronary artery disease: demographics,
      hemodynamics and angiographic features.
AB  - Left main coronary artery disease carries a poor prognosis. The etiology of
      isolated and significant left main coronary artery (ILMCA) disease is not well
      understood. Studies so far were limited by small numbers. The authors identified
      46 patients with ILMCA disease from their database over 10 years (group I) and
      compared them with 83 consecutive patients undergoing catheterization (group II).
      They also compared patients with ostial vs distal ILMCA disease. Group I
      represented 0.1% of catheterization patients. The demographic profile and
      atherosclerotic risk factor profile of the 2 groups as well as ostial and distal
      ILMCA disease were compared. This is the largest study of ILMCA disease. Risk
      factors for atherosclerosis were commonly seen. Nonatherosclerotic causes of
      ILMCA disease were not seen. This study suggests coronary atherosclerosis as the
      predominant cause of ILMCA disease. ILMCA disease is more common in women.
      Diabetes is more commonly associated with distal ILMCA lesion. There is a trend
      suggesting that ostial ILMCA lesion is more common in smokers and women.

PMID- 17022384
TI  - Increased carotid artery stiffness without atherosclerotic change in patients
      with aortic dissection.
AB  - The arterial properties and pathogenesis of aortic dissection remain obscure. To
      examine the arterial properties of patients with aortic dissection, the authors
      studied the ultrasonographic characteristics of the carotid artery in patients
      with an aortic dissection (AD, n = 86), and compared these findings with data of
      patients suffering from arteriosclerosis obliterans (ASO, n = 151), coronary
      artery disease (CAD, n = 163), and with healthy controls (HC, n = 77).
      Atherosclerotic intimal changes, such as intima-media thickness (IMT) and plaque
      formation, were milder in AD than in ASO or CAD (IMT: 0.83 +/- 0.16 vs 0.93 +/-
      0.20/0.86 +/- 0.17 mm, p < 0.05; plaque number: 0.6 +/- 1.1 vs 2.7 +/- 2.4/2.5 +/
      2.1, p <0.05). Luminal diameter in AD, ASO, and CAD was significantly higher
      than in HC. The luminal distensibility in AD was decreased compared with HC but
      was the same as in ASO and CAD. Intra-AD group analysis showed that in patients
      with an intramural hematoma (IMH) or a dissection with a thrombosed false lumen
      (TLF) the IMT was higher than in patients with a classic dissection. In addition,
      plaque formation was more severe in AD patients with a coexisting abdominal
      aortic aneurysm (AAA). Reduced distensibility without severe intimal disease was
      found in AD. These findings suggest that patients with AD may have several
      arterial alterations, including structural abnormalities. Patients with IMH, TFL,
      or coexisting AAA may differ from patients who have a classic type of dissection
      or who do not have AAA, in terms of arterial characteristics including intimal
      disease and wall elastic property, and the initiating cause of the dissection.

PMID- 17022385
TI  - Predicting the risk of rupture of abdominal aortic aneurysms by utilizing various
      geometrical parameters: revisiting the diameter criterion.
AB  - The authors estimated noninvasively the wall stress distribution for actual
      abdominal aortic aneurysms (AAAs) in vivo on a patient-to-patient basis and
      correlated the peak wall stress (PWS) with various geometrical parameters. They
      studied 39 patients (37 men, mean age 73.7 +/- 8.2 years) with an intact AAA
      (mean diameter 6.3 +/- 1.7 cm) undergoing preoperative evaluation with spiral
      computed tomography (CT). Real 3-dimensional AAA geometry was obtained from image
      processing. Wall stress was determined by using a finite-element analysis. The
      aorta was considered isotropic with linear material properties and was loaded
      with a static pressure of 120.0 mm Hg. Various geometrical parameters were used
      to characterize the AAAs. PWS and each of the geometrical characteristics were
      correlated by use of Pearson's rank correlation coefficients. PWS varied from
      10.2 to 65.8 N/cm2 (mean value 37.1 +/- 9.9 N/cm2). Among the geometrical
      parameters, the PWS was well correlated with the mean centerline curvature, the
      maximum centerline curvature, and the maximum centerline torsion of the AAAs. The
      correlation of PWS with maximum diameter was nonsignificant. Multiple regression
      analysis revealed that the mean centerline curvature of the AAA was the only
      significant predictor of PWS and subsequent rupture risk. This noninvasive
      computational approach showed that geometrical parameters other than the maximum
      diameter are better indicators of AAA rupture.

PMID- 17022386
TI  - The relationship between beta-receptor sensitivity and nocturnal blood pressure
      and heart rate recovery in normotensive people.
AB  - This study examined the relationship between nocturnal blood pressure (BP)
      dipping and chronotropic dose25 (CD25) as an indicator of beta-adrenergic
      receptor functioning in normotensive people. In addition, the authors evaluated
      the influence of beta-receptor functioning on heart rate recovery after exercise.
      The sample consisted of 41 participants (18 men, 23 women). Ambulatory BP
      monitoring took place in each patient's home. On a separate occasion, beta
      adrenergic receptor sensitivity was determined by response to isoproterenol
      infusion. Heart rate (HR) recovery was defined as the change from peak HR to that
      measured after 1 and 2 minutes of recovery. Relationships between dipping and
      CD25 were found such that participants with higher CD25 values had less nocturnal
      decline in systolic BP, diastolic BP, and mean arterial pressure (r = -0.445, 
      0.533, -0.510, respectively; p < 0.004, 0.001, 0.001, respectively). Heart rate
      recovery at 1 and 2 minutes after exercise was 28.8 +/- 5 and 49.9 +/- 6
      beats/minute, respectively. Participants with higher CD25 values had more heart
      rate decline during the first 2 minutes of recovery (r = 0.407, p < 0.008). In
      addition, heart rate recovery was inversely related to systolic, diastolic, and
      mean nocturnal blood pressure dipping (r = -0.348, -0.432, -0.408, respectively,
      p<0.028, 0.005, 0.009, respectively). Normotensive people with an abnormal
      circadian pattern of blood pressure may have desensitized beta-adrenergic
      receptors. This desensitization may contribute to blunted nocturnal blood
      pressure and increased heart rate recovery as measured at 2 minutes following
      exercise testing.

PMID- 17022387
TI  - Unusual retrograde aortic arch dissection during percutaneous coronary
      intervention: A case report.
AB  - Coronary dissection is one of the most frequently occurring complications during
      coronary interventional procedures. However, extensive coronary dissection
      retrograde to the coronary sinus of Valsalva and to the arch of aorta is very
      rarely observed. The authors report a case of retrograde coronary dissection
      extending into the arch of aorta. Management and coronary angiography at 6-month
      follow-up are discussed.

PMID- 17022388
TI  - Rupture of a nonaneurysmal aorta secondary to Staphylococcus aortitis.
AB  - Infectious aortitis has become increasingly uncommon and, when diagnosed,
      typically occurs in an immunocompromised elderly male with a history of
      Staphylococcus or Salmonella infection and underlying atheromatous cardiovascular
      disease. The authors report a case of a 74-year-old man with aortitis complicated
      by rupture secondary to Staphylococcus aureus infection. The patient presented
      with worsening abdominal pain and fever after being discharged from the emergency
      room 2 weeks before with back pain and leukocytosis diagnosed as urinary tract
      infection and bronchitis. Computed tomography (CT) imaging of the retroperitoneum
      on the first visit appeared normal. Repeat CT scan on the subsequent visit
      revealed a contained rupture of a nonaneurysmal aorta at the level of the
      diaphragm. The patient was taken to the operating room emergently for repair. An
      infected periaortic hematoma and a 1 cm perforation in the posterior aorta were
      found. The aorta was excised and the area debrided. Revascularization was
      performed using a 22 mm extruded polytetrafluoroethylene (ePTFE) interposition
      graft placed in situ. This case demonstrates that a high index of suspicion is
      required in diagnosing infectious aortitis and that the diagnosis may be delayed
      in many cases. Additionally, it may not be uncommon for the infected aorta to
      rupture without prior aneurysm formation.

PMID- 17022389
TI  - Lipoma of the interatrial septum in a patient with chronic atrial fibrillation: A
      case report.
AB  - The authors report on a 70-year-old woman with chronic atrial fibrillation that
      was hospitalized for digitalis intoxication and incidentally was found to have an
      interatrial lipoma. The diagnosis was established by transesophageal
      echocardiography, computed tomography (CT) scanning, and magnetic resonance
      imaging (MRI). Owing to the asymptomatic character and the benign nature of the
      tumor, a decision for conservative management was made.

PMID- 17022390
TI  - Sarcomatous pleural mesothelioma metastatic to left ventricular endocardium.
AB  - A 71-year-old man, a cigarette smoker with long-term asbestos exposure, developed
      multifocal malignant sarcomatous pleural mesothelioma that metastasized to the
      left ventricular endocardium without invading pericardium, myocardium, or the
      contiguous pulmonary vein. This is the first reported case of malignant pleural
      mesothelioma to metastasize in such a manner.

PMID- 17022391
TI  - Beneficial effect of gabexate mesilate on microscopic polyangiitis with renal
      dysfunction and pulmonary hemorrhage: A case report.
AB  - Corticosteroids and cyclophosphamide are the mainstay of the treatment of
      microscopic polyangiitis involving pulmonary hemorrhage or rapidly progressive
      glomerulonephritis. However, patients with advanced age are unable to tolerate
      this combined therapy, because of a relatively high incidence of side effects
      including infection, hemorrhagic cystitis, and bone marrow suppression. The
      authors encountered an 80-year-old patient with pulmonary hemorrhage and renal
      dysfunction ascribed to microscopic polyangiitis and achieved successful
      treatment by employing gabexate mesilate in addition to corticosteroids. The
      present case suggests that gabexate mesilate may be a therapeutic option for
      microscopic polyangiitis with progressive renal failure and pulmonary hemorrhage.

PMID- 17022392
TI  - Use of gadolinium-based angiography for renal artery stenting in a patient with
      renal insufficiency: A case report.
AB  - The number of percutaneous diagnostic and interventional procedures performed
      continues to increase. Despite the use of various methods to reduce the incidence
      of contrast-induced nephropathy, the development of renal failure remains a
      significant problem with iodinated-based contrast agents. Patients with a
      baseline renal insufficiency are at considerably higher risk of permanent renal
      deterioration following exposure to iodinated contrast. The authors report a
      successful case of percutaneous stenting of the renal artery using a gadolinium
      based contrast agent in a high-risk patient with renal insufficiency.

PMID- 17022393
TI  - Dynamic modeling of food-chain accumulation of brominated flame retardants in
      fish from the Ebro River Basin, Spain.
AB  - Since the 1980s, brominated flame retardants (BFRs) have been detected in air,
      sewage sludge, sediment, fish, shellfish, birds, and mammals, including humans.
      However, model studies regarding BFR food-chain accumulation are scarce. In the
      present study, the accumulation of hexabromocyclododecane and brominated diphenyl
      ethers (BDEs) 47, 153, 154, and 183 in benthivorous barbel (Barbus graellsii) and
      pelagic bleak (Alburnus alburnus) from four locations in the Ebro river basin in
      Spain was modeled using a first-order, one-compartment model with sediment
      interaction. The model accounted for BFR uptake from water, ingested sediment,
      and food; release via water and feces; growth; and in situ binding of BFRs to
      black carbon. Rate constants were derived from allometric regressions. For most
      BFRs, dynamically modeled biota-sediment accumulation factors (BSAFs) were close
      to measured values, whereas steady-state model BSAFs were too high, especially
      for BDEs 153, 154, and 183. Differences between BSAFs for individual fish were
      explained by differences in age, growth, and feeding behavior. On average,
      modeled BSAFs for barbel were 50% higher than those for bleak because of extra
      BFR uptake through sediment ingestion and older age of barbel specimens.

PMID- 17022394
TI  - Laboratory persistence and fate of fluoxetine in aquatic environments.
AB  - The persistence and fate of fluoxetine, a selective serotonin reuptake inhibitor,
      has been investigated in laboratory-scale experiments, including studies with
      various aqueous solutions, water/sediment systems, and activated sludge-amended
      medium. The samples were placed in the dark and/or in a growth chamber fitted
      with fluorescent lamps simulating the ultraviolet output of sunlight. Over a
      period of 30 d, fluoxetine was hydrolytically and photolytically stable in all
      aqueous solutions except synthetic humic water (pH 7), in which the degradation
      rate was increased by approximately 13-fold in comparison with buffered solutions
      at the same pH. Fluoxetine rapidly dissipated from the aqueous phase in
      water/sediment systems, primarily because of distribution to sediments. The
      dissipation rate from the aqueous phase was similar between light and dark
      systems, indicating a low contribution of photodegradation to the dissipation of
      fluoxetine in this system. The potential impact of fluoxetine in aquatic
      environments would be decreased because of adsorption to sediments. Based on
      results of ready-biodegradability investigations, fluoxetine would not be
      expected to rapidly biodegrade in wastewater treatment plants. A photoproduct was
      detected only in a sample of synthetic humic water and was identified as
      norfluoxetine formed by demethylation. Results indicate that fluoxetine is
      relatively recalcitrant to hydrolysis, photolysis, and microbial degradation and
      that it is rapidly removed from surface waters by adsorption to sediment, where
      it appears to be persistent.

PMID- 17022395
TI  - Concentrations and partitioning of polychlorinated biphenyls in the surface
      waters of the southern Baltic Sea-seasonal effects.
AB  - In the marine environment, the partitioning of hydrophobic organic contaminants,
      such as polychlorinated biphenyls (PCBs), between the dissolved and suspended
      matter phases in the water column plays a fundamental role in determining
      contaminant fate (e.g., air-water exchange or food-chain uptake). Despite the
      pronounced seasonality in physical, chemical, and biological conditions in
      temperate marine ecosystems, little is known about the seasonality in organic
      contaminant partitioning behavior. Surface water from the western Baltic Sea was
      sampled regularly during an 18-month period between February 2003 and July 2004.
      The concentrations of seven PCB congeners were determined in the dissolved and
      particulate organic carbon (POC) phases. An inverse relationship was found
      between K(POC) (i.e., the ratio between the POC-normalized PCB concentration
      [pg/kg POC] and the dissolved concentration [pg/L]) and temperature. The decrease
      in the water temperature of 20 degrees C between summer and winter resulted in an
      increase in K(POC) by a factor of approximately five. The POC-normalized PCB
      concentrations were higher in winter than in summer by a factor of 9 to 20. This
      reflected the higher K(POC) and somewhat greater PCB concentrations in the
      dissolved phase, and it could have consequences for bioaccumulation of these
      chemicals in aquatic food webs. The results demonstrate a clear seasonality in
      contaminant partitioning in the temperate marine environment that should be
      accounted for when interpreting field data or modeling contaminant fate.

PMID- 17022396
TI  - Evaluation of potential toxicity and bioavailability of chromium in sediments
      associated with chromite ore processing residue.
AB  - Recent studies by researchers at the U.S. Environmental Protection Agency and
      U.S. Geological Survey have evaluated the toxicity of Cr in freshwater and marine
      sediments, primarily during laboratory studies in which clean sediments were
      spiked with Cr. Results of those studies showed that Cr is relatively insoluble
      and nontoxic when present in the trivalent form, Cr(III), rather than in the more
      soluble and more toxic hexavalent form, Cr(VI). The studies concluded that Cr
      toxicity should be low in sediments with measurable concentrations of acid
      volatile sulfide (AVS), because AVS is formed only in anoxic sediments and Cr(VI)
      is thermodynamically unstable under such conditions. The present study evaluates
      the toxicity and bioavailability of Cr in sediments associated with chromite ore
      processing residue (COPR). Ten stations were sampled in the Hackensack River (NJ,
      USA) to represent a wide range of total Cr concentrations (199-3,970 mg/kg) with
      minimal interference from potentially toxic, co-occurring chemicals. Sediment
      toxicity was evaluated using two amphipod tests: The 10-d Ampelisca abdita test
      (survival as endpoint), and the 28-d Leptocheirus plumulosus test (survival and
      biomass as endpoints). Measurable concentrations of AVS were present at eight
      stations, and nearly all Cr was present as Cr(III). In addition, results of
      electron-microprobe analyses showed that most Cr was associated with phases in
      which Cr has limited bioavailability (i.e., chromite and iron oxide). Sediment
      toxicity showed no correlation with concentrations of total Cr, and the maximum
      no-effect concentration for total Cr was estimated as 1,310 mg/ kg. These results
      indicate that Cr can be present in sediments associated with COPR at highly
      elevated concentrations without causing sediment toxicity.

PMID- 17022397
TI  - Sorption of p-nitrophenol on two Chinese soils as affected by copper.
AB  - Heavy metals and organic contaminants often coexist in soils. However, very
      little information is available regarding the effect of metals on the sorption of
      organic contaminants onto soils and/or of organic contaminants on metal sorption.
      In the present study, the effect of Cu on the sorption of p-nitrophenol on two
      Chinese soils was investigated using a batch-equilibration method for three
      conditions: Copper and p-nitrophenol were sorbed simultaneously, either Cu orp
      nitrophenol was sorbed previously, or the soil colloidal phase was removed in
      part previously. The results suggested that Cu suppressed the sorption ofp
      nitrophenol on soils, whereas p-nitrophenol had little effect on Cu sorption
      because of the higher affinity of Cu for soils. Mechanisms of the Cu suppression
      effect were suggested by the results. First, large hydrated Cu occupy the
      siloxane surface of soils and prevent nonspecific interaction between p
      nitrophenol and soils. Second, the soil colloidal phase is an effective adsorbent
      of p-nitrophenol; thus, more p-nitrophenol is retained in the aqueous phase. In
      addition, the aggregation of the colloidal particles may occur, which blocks soil
      pores, thereby decreasing the sorption of p-nitrophenol on the solid soil phase.
      Third, x-ray absorption spectroscopy revealed that Cu forms inner-sphere
      complexes with the carboxyl and hydroxyl functional moieties of the soil
      particles (clay minerals and organic matter). Fourier-transform infrared
      spectroscopy study indicated that these groups also react with p-nitrophenol
      through H-bond formation. These results suggested that Cu and p-nitrophenol have
      common sorption sites, at least in the soil organic matter domain, which is
      partially responsible for the observed overall Cu suppression effect.

PMID- 17022398
TI  - Temporal changes of ethoxyresorufin-o-deethylase (EROD) activities and lysosome
      accumulation in intestine of fish on chronic exposure to dietary benzo[a]pyrene:
      linking erod induction to cytological effects.
AB  - Temporal changes of intestinal and hepatic ethoxyresorufin-O-deethylase (EROD)
      activities and quantitative changes of secondary and tertiary (e.g., 2 degrees/3
      degrees) lysosomes in enterocytes were compared for the juvenile grouper
      (Epinephelus coioides) on chronic exposure to foodborne benzo[a]pyrene (BaP) at
      two environmentally realistic levels (0.25 and 12.5 microg/g fish/d) over a four
      week exposure and four-week depuration period. Intestinal EROD induction was
      rapid (within 3 d) and sustained in the BaP-exposed fish, while a fast recovery
      (within one week) was observed on withdrawal of BaP intake. A dose-response
      relationship was demonstrated between intestinal EROD activities and the levels
      of foodborne BaP. Conversely, hepatic EROD induction was weak and subsided
      rapidly in the exposed fish, signifying that hepatic EROD activity is not a good
      indicator of oral intake of BaP. Significant increase of 2 degrees/3 degrees
      lysosomes, as measured by Vv(lysosome, mucosa), was detected in young enterocytes
      of fish in the high-dosing group (12.5 microg/g fish/d) at exposure day 3 and
      persisted until recovery week 2. Importantly, intestinal EROD activity was
      significantly correlated to 2 degrees/3 degrees lysosome accumulation in
      enterocytes (r = 0.571, p < 0.001). These results further corroborate our earlier
      findings that induction of EROD activities in fish do not merely indicate
      exposure to BaP but also are correlated to harmful biological effects. We
      recommend the use of these two biochemical and cytological changes in intestines
      as specific biomarkers to indicate current and recent exposure of fish to BaP via
      oral intake.

PMID- 17022399
TI  - An evaluation of cause-effect relationships between polychlorinated biphenyl
      concentrations and sediment toxicity to benthic invertebrates.
AB  - Cause-effect sediment-quality benchmarks for the protection of benthic
      invertebrates are needed for polychlorinated biphenyls (PCBs) to support
      predictive risk assessments and retrospective evaluations of the causes of
      observed sediment toxicity. An in-depth evaluation of PCB aquatic toxicity and
      organic carbon partitioning was conducted to predict sediment effect
      concentrations using the equilibrium partitioning (EqP) approach. This evaluation
      was limited to invertebrate toxicity data, because PCBs may exert toxicity to
      invertebrates and fish via different toxicological mechanisms. As a result of
      differences in organic carbon partitioning among PCBs of differing levels of
      chlorination, the estimated EqP benchmarks increase with increasing degree of
      chlorination for various commercial and environmental PCB mixtures. Studies of
      spiked sediment toxicity using PCBs were reviewed, and their results generally
      were consistent with EqP predictions. Additionally, toxicity and benthic
      community data were reviewed for eight PCB-contaminated sites; these data also
      showed agreement with EqP predictions. None of these lines of evidence supports
      previously proposed, empirical sediment-quality guidelines for PCBs. Reasons for
      the lack of agreement between cause-effect and association-based benchmarks are
      discussed, and areas of future research to further refine EqP predictions for
      PCBs are identified.

PMID- 17022400
TI  - Evaluating cytochrome p450 in lesser scaup (Aythya affinis) and tree swallow
      (Tachycineta bicolor) by monooxygenase activity and immunohistochemistry:
      possible nonlethal assessment by skin immunohistochemistry.
AB  - Six-month-old lesser scaup (Aythya affinis) and nestling tree swallows
      (Tachycineta bicolor) were injected intraperitoneally with beta-naphthoflavone
      (BNF) in corn oil or in vehicle alone. Liver samples were taken and stored at -80
      degrees C until microsome preparation and monooxygenase assay. Skin samples were
      placed in buffered formalin for subsequent immunohistochemical (IHC) analysis for
      cytochrome P4501A (CYP1A). Lesser scaup treated with BNF at 20 or 100 mg/kg body
      weight showed approximately 6- to 18-fold increases in four monooxygenases
      (benzyloxyresorufin-O-dealkylase, ethoxyresorufin-O-dealkylase, methoxyresorufin
      O-dealkylase, and pentoxyresorufin-O-dealkylase). No IHC response was observed
      for CYP1A in the skin of vehicle-injected ducks, whereas in the skin from BNF
      treated ducks, the positive IHC response was of similar magnitude for both dose
      levels of BNF. Tree swallows injected with BNF at 100 mg/kg, but not at 20 mg/kg,
      showed significant increases (approximately fivefold) in hepatic microsomal O
      dealkylase activities. Cytochrome P4501A was undetectable by IHC response in skin
      from corn oil-treated swallows, but positive IHC responses were observed in the
      skin of one of five swallows at 20 mg/kg and four of five swallows at 100 mg/kg.
      Although these data do not allow construction of significant dose-response
      curves, the IHC responses for CYP1A in skin support the possible use of this
      nonlethal approach for biomonitoring contaminant exposure of birds. In addition,
      the CYP1A signal observed at the bases of emerging feathers suggest that these
      might provide less invasive sampling sites for IHC analysis of CYP1A.

PMID- 17022401
TI  - Selenium absorption, distribution, and excretion in white sturgeon orally dosed
      with l-selenomethionine.
AB  - The usefulness of a newly developed, combined technique consisting of esophageal
      intubation, dorsal aortic cannulation, and urinary catheterization to deliver Se
      orally and to monitor Se uptake, accumulation, and excretion in white sturgeon
      (Acipenser transmontanus) was explored. Groups of five yearling sturgeon (1-2 kg)
      each were intubated with 0 (sham), 250, 500, or 1,000 microg Se/kg body weight in
      the form of L-selenomethionine, an ecologically relevant organic form of Se.
      Selenium concentrations in whole blood, plasma, and red blood cells did not
      change in the sham group but began to rise within 2 h postintubation in the other
      groups, and levels remained near maximum concentrations throughout the 48-h
      sampling period. Average urinary Se excretion rates over the entire 48-h period
      were 0.05, 0.46, 0.61, and 2.15 microg Se/kg/h in sturgeon intubated with 0, 250,
      500, and 1,000 microg Se/kg, respectively. Selenium excretion rates were highest
      within the first 6 h in all treatment groups except the sham group. Selenium
      concentrations in the liver were positively correlated with the intubated Se
      dosage.

PMID- 17022402
TI  - Kinetics of ptaquiloside hydrolysis in aqueous solution.
AB  - Ptaquiloside (PTA) is a well-known toxin produced by the bracken fern (Pteridium
      aquilinum (L.) Kuhn). It is proposed that PTA from bracken stands can leach
      through soil and sediments into drinking-water reservoirs, thus representing a
      concern for human health. To predict the persistence of the toxin, a full
      understanding of the PTA degradation in aqueous environments is important. The
      kinetics of PTA hydrolysis was examined at 22 degrees C in aqueous buffered
      solutions (pH 2.88-8.93). The reaction was found to follow first-order kinetics
      with respect to PTA at all pH and temperature conditions. At pH lower than 4.43
      (+/- 0.32), the reaction is acid-mediated, whereas the reaction is base-mediated
      at pH higher than 6.39 (+/- 0.28). The rate constants for the acid-catalyzed,
      base-catalyzed, and neutral hydrolysis are 25.70 (+/- 0.96), 4.83 (+/- 0.03) X
      10(4), and 9.49 (+/- 6.02) x 10(-4) h(-1), respectively. The PTA hydrolysis at pH
      4.46 is strongly dependent on temperature, with an activation energy of 74.4 (+/-
      2.6) kJ mol(-1). Stoichiometric calculations, reaction kinetics, and ultraviolet
      visible spectrophotometry strongly indicates the formation of an intermediary
      compound at pH 5.07 and 6.07 via a mechanism comprising two first-order
      consecutive reactions. Ptaquiloside has the lowest rate of hydrolysis at slightly
      acidic pH and low temperatures. Therefore, because PTA is not sorbed in soil,
      slightly acidic sandy soils in cold climates are most prone to PTA leaching to
      deeper soil layers and aquifers.

PMID- 17022403
TI  - Degradation of btex compounds under iron-reducing conditions in contaminated
      aquifer microcosms.
AB  - The potential for benzene, toluene, ethylbenzene, and xylenes (BTEX) degradation
      was investigated in microcosms inoculated with sediment and groundwater from a
      polluted iron-reducing aquifer. Benzene, toluene, and each of the three xylene
      isomers were degraded by the intrinsic microorganisms under iron-reducing
      conditions, but there was no removal of ethylbenzene. This work provides the
      first evidence for para-xylene degradation by dissimilatory iron-reducing
      bacteria. Microcosms adapted to benzene, toluene, or m-xylene were subsequently
      exposed to a different BTEX compound, which was degraded without lag phase,
      suggesting that the same group of bacteria could be involved in the removal of
      more than one BTEX compound. Furthermore, when microcosms were exposed to a
      mixture of BTEX, concurrent degradation of benzene and toluene, but not of meta
      xylene and ethylbenzene, was observed. These results suggest that, under the
      influence of the plume of pollution, an iron-reducing microbial community able to
      degrade multiple aromatic compounds has developed.

PMID- 17022404
TI  - Can highly hydrophobic organic substances cause aquatic baseline toxicity and can
      they contribute to mixture toxicity?
AB  - Effect concentrations for aquatic baseline toxicity generally decrease with
      increasing log octanol-water partition co-efficient (Kow) values of up to 5 to 6,
      whereas less is known about the baseline toxicity of organic chemicals with log
      Kow values above 6. A physicochemical analysis of the dissolution process for
      organic chemicals was combined with reported baseline toxicity data, leading to
      the following conclusions. First, no absolute hydrophobicity cutoff exists for
      baseline toxicity at a log Kow value of 6, because aquatic baseline toxicity for
      fish and algae was observed for chemicals with log Kow values greater than 6.5
      and with effect concentrations less than 10 microg/L. Second, the baseline
      toxicity of hydrophobic organic substances was exerted at a relatively constant
      chemical activity of 0.01 to 0.1. Finally, organic chemicals with high melting
      points cannot provide sufficient chemical activity to exert baseline toxicity
      when considered as individual, pure chemicals. However, such substances are still
      expected to contribute to baseline toxicity when part of a complex mixture.

PMID- 17022405
TI  - Neuropharmaceuticals in the environment: mianserin-induced neuroendocrine
      disruption in zebrafish (Danio rerio) using cDNA microarrays.
AB  - Because of their environmental occurrence and high biological activity, human
      pharmaceuticals have received increasing attention from environmental and health
      agencies. A major bottleneck in their risk assessment is the lack of relevant and
      specific effect data. We developed an approach using gene expression analysis in
      quantifying adverse effects of neuroendocrine pharmaceuticals in the environment.
      We studied effects of mianserin on zebrafish (Danio rerio) gene expression using
      a brain-specific, custom microarray, with real-time polymerase chain reaction as
      confirmation. After exposure (0, 25, and 250 microg/L) for 2, 4, and 14 d, RNA
      was extracted from brain tissue and used for microarray hybridization. In
      parallel, we investigated the impact of exposure on egg production,
      fertilization, and hatching. After 2 d of exposure, microarray analysis showed a
      clear effect of mianserin on important neuroendocrine-related genes (e.g.,
      aromatase and estrogen receptor), indicating that antidepressants can modulate
      neuroendocrine processes. This initial neuroendocrine effect was followed by a
      "late gene expression effect" on neuronal plasticity, supporting the current
      concept regarding the mode of action for antidepressants in mammals. Clear
      adverse effects on egg viability were seen after 14 d of exposure at the highest
      concentration tested. Based on the specific molecular impact and the effects on
      reproduction, we conclude that further investigation of the adverse effects on
      the brain-liver-gonad axis is needed for a correct ecological risk assessment of
      antidepressants.

PMID- 17022406
TI  - Subacute effects of transgenic crylab bacillus thuringiensis corn litter on the
      isopods Trachelipus rathkii and armadillidium nasatum.
AB  - Laboratory studies were conducted to investigate the subacute effects of
      transgenic Cry1Ab corn leaf material containing Bacillus thuringiensis (Bt)
      protein on the terrestrial isopods Trachelipus rathkii and Armadillidium nasatum.
      Survival and growth were measured for eight weeks in isopods fed leaf material of
      two Bt11 corn varieties, two Monsanto 810 (Mon810) corn varieties, and the
      isolines of each. Total lipid and protein content of the organisms was measured
      to examine effects on energetic reserves. Armadillidium nasatum individuals in
      all treatments responded similarly. For T. rathkii, no statistically significant
      effect of Bt was observed, but statistical differences were observed in growth
      between hybrids. Protein and sugar content of the food were found to be
      correlated with the differences in growth for T. rathkii. Total protein content
      was higher in T. rathkii and A. nasatum fed material with higher protein and
      sugar content. A trend toward less growth in T. rathkii on Bt corn varieties
      versus their isolines triggered a concentration-response assay with purified
      Cry1Ab protein. No adverse effects of purified Bt protein were observed. These
      results indicate that little hazard to T. rathkii and A. nasatum from Bt corn
      leaf material from these hybrids exists. However, nutritional differences in corn
      hybrids contributed to differences in isopod growth.

PMID- 17022407
TI  - Interlaboratory evaluation of Hyalella azteca and Chironomus tentans short-term
      and long-term sediment toxicity tests.
AB  - Methods for assessing the long-term toxicity of sediments to Hyalella azteca and
      Chironomus tentans can significantly enhance the capacity to assess sublethal
      effects of contaminated sediments through multiple endpoints. Sublethal tests
      allow us to begin to understand the relationship between short-term and long-term
      effects for toxic sediments. We present an interlaboratory evaluation with long
      term and 10-d tests using control and contaminated sediments in which we assess
      whether proposed and existing performance criteria (test acceptability criteria
      [TAC]) could be achieved. Laboratories became familiar with newly developed, long
      term protocols by testing two control sediments in phase 1. In phase 2, the 10-d
      and long-term tests were examined with several sediments. Laboratories met the
      TACs, but results varied depending on the test organism, test duration, and
      endpoints. For the long-term tests in phase 1, 66 to 100% of the laboratories
      consistently met the TACs for survival, growth, or reproduction using H. azrteca,
      and 70 to 100% of the laboratories met the TACs for survival and growth,
      emergence, reproduction, and hatchability using C. tentans. In phase 2, fewer
      laboratories participated in long-term tests: 71 to 88% of the laboratories met
      the TAC for H. azteca, whereas 50 to 67% met the TAC for C. tentans. In the 10-d
      tests with H. azteca and C. tentans, 82 and 88% of the laboratories met the TAC
      for survival, respectively, and 80% met the TAC for C. tentans growth. For the 10
      d and long-term tests, laboratories predicted similar toxicity. Overall, the
      interlaboratory evaluation showed good precision of the methods, appropriate
      endpoints were incorporated into the test protocols, and tests effectively
      predicted the toxicity of sediments.

PMID- 17022408
TI  - Multistep bioassay to predict recolonization potential of emerging parasitoids
      after a pesticide treatment.
AB  - Neurotoxic pyrethroid insecticides are widely used for crop protection, and
      lethal and sublethal perturbations can be expected in beneficial insects. Under
      laboratory conditions, the lethal and sublethal effects of deltamethrin on the
      aphid parasitoid Diaeretiella rapae M'Intosh (Hymenoptera: Braconidae) were
      studied at the mummy stage and in emerging adults. Following a multistep
      bioassay, analyses were aimed at evaluating the effects of deltamethrin at
      various crucial steps in the recolonization process following a deltamethrin
      treatment: Parasitoid pupal development (emergence from the mummies), adult
      survival, and host-searching capacity. A four-armed olfactometer was used to
      investigate the effect of deltamethrin on host-searching behavior (a range of
      concentrations causing 0.4-79.4% mortality was tested), and a Potter tower was
      used to test the deltamethrin effect with a realistic application method (four
      concentrations were tested: 0.5, 5.0, 6.25, and 50 g active ingredient
      [a.i.]/ha). Deltamethrin reduced the percentage of emergence from mummies, but
      only when exposed to the 50 g a.i./ha concentration. However, for all
      concentrations tested, the insecticide induced a decrease in longevity after
      emergence from sprayed mummies and significant adult mortality when parasitoids
      walked on fresh residues on leaves. Indices were defined and predicted a high
      mortality and, thus, reduction of recolonization capacities. However,
      deltamethrin had no effect on orientation behavior toward aphid-infested plants
      for adults that survived a residual exposure to the insecticide. The impact of
      deltamethrin on recolonization via pupal emergence and interest in the
      methodology used are discussed.

PMID- 17022409
TI  - Toxicity of ozonated seawater to marine organisms.
AB  - Ballast water transport of nonindigenous species (NIS) is recognized as a
      significant contributor to biological invasions and a threat to coastal
      ecosystems. Recently, the use of ozone as an oxidant to eliminate NIS from
      ballast while ships are in transit has been considered. We determined the
      toxicity of ozone in artificial seawater (ASW) for five species of marine
      organisms in short-term (< or = 5 h) batch exposures. Larval topsmelt (Atherinops
      affinis) and juvenile sheepshead minnows (Cyprinodon variegatus) were the most
      sensitive to oxidant exposure, and the mysid shrimp (Americamysis bahia) was the
      most sensitive invertebrate. Conversely, benthic amphipods (Leptocheirus
      plumulosus and Rhepoxinius abronius) were the least sensitive of all species
      tested. Mortality from ozone exposure occurred quickly, with median lethal times
      ranging from 1 to 3 h for the most sensitive species, although additional
      mortality was observed 1 to 2 d following ozone exposure. Because ozone does not
      persist in seawater, toxicity likely resulted from bromide ion oxidation to
      bromine species (HOBr and OBr-), which persist as residual toxicants after at
      least 2 d of storage. Total residual oxidant (TRO; as Br2) formation resulting
      from ozone treatment was measured in ASW and four site-specific natural
      seawaters. The rate of TRO formation correlated with salinity, but dissolved
      organic carbon and total dissolved nitrogen did not affect TRO concentrations.
      Acute toxicity tests with each water over 48 h using mysid shrimp, topsmelt, and
      sheepshead minnows yielded results similar to those of batch exposure. Addition
      of sodium thiosulfate (Na2S2O3) to ozonated waters resulted in TRO elimination
      and survival of all organisms. Our results provide necessary information for the
      optimization of an efficacious ozone ballast water treatment system.

PMID- 17022410
TI  - Selenium bioaccumulation in Chlamydomonas reinhardtii and subsequent transfer to
      Corbicula fluminea: role of selenium speciation and bivalve ventilation.
AB  - The uptake of Se by the freshwater alga Chlamydomonas reinhardtii and the
      subsequent transfer to the Asiatic clam Corbicula fluminea was investigated. The
      objective was to investigate the bioavailability of algal-bound Se for C.
      fluminea while taking into account Se speciation and bivalve ventilation. First,
      uptake rates of waterborne Se (selenite, selenate, and selenomethionine) in the
      algae during a 1-h exposure period were determined for a range of concentrations
      up to 2,000 microg/L. Fluxes for selenite uptake were constant in the range of
      concentrations tested, whereas fluxes for selenate and selenomethionine uptake
      decreased with increasing concentrations, suggesting a saturated transport system
      at high concentrations (approximately 1,000 microg/L for selenate and 100
      microg/L for selenomethionine). These data were used to set the algal
      contamination for the study of trophic transfer to the clam. Three parameters
      were studied: The Se form, the algal density, and the Se burden in the algae. The
      results show that for a fixed algal density, an Se-contaminated algal diet does
      not modify ventilation. In this case, the driving factor for ventilation is the
      algal density, with ventilation being enhanced for low algal densities. On the
      basis of ventilatory flow rate measurements and Se burdens in algae, it was found
      that bioaccumulation of Se in C. fluminea was proportional to the total quantity
      of Se passing through the whole organism, but with a lesser extraction
      coefficient for selenomethionine than for the inorganic forms. These results
      underline the importance of both physiological factors and speciation in
      understanding the trophic transfer of Se.

PMID- 17022411
TI  - Contamination by polybrominated diphenyl ethers and persistent organochlorines in
      catfish and feed from Mekong River Delta, Vietnam.
AB  - Commercial feeds for aquaculture and catfish samples were collected from the
      Mekong River Delta, Vietnam, for determination of polybrominated diphenyl ethers
      (PBDEs) and selected persistent organochlorines, including polychlorinated
      biphenyls (PCBs), DDT and its metabolites (DDTs), chlordane-related compounds
      (CHLs), hexachlorocyclohexane isomers (HCHs), and hexachlorobenzene (HCB). The
      most abundant contaminants were DDTs, with concentrations ranging from 10 to 700
      ng/g lipid weight, followed by PCBs (1.0-80 ng/g), CHLs (<0.01-8.2 ng/g), PBDEs
      (0.12-3.7 ng/g), HCHs (<0.03-5.1 ng/g), and HCB (<0.07-3.2 ng/g). Polybrominated
      diphenyl ethers were detected in all samples, suggesting their widespread
      contamination in the region. However, PBDE contamination levels in the present
      catfish specimens were low in comparison to levels worldwide. Interestingly,
      residue levels of all the contaminants were significantly higher in catfish
      collected near a municipal dumping site compared to farmed catfish. This suggests
      that runoffs from the dumping site during floods and rains may have brought
      pollutants to the surrounding areas. Contamination pattern in aquaculture feeds
      revealed elevated levels of PCBs and PBDEs in samples from foreign companies,
      perhaps implying their higher residues in some imported ingredients. Congener
      profiles of PBDEs and PCBs demonstrated similarity between the farmed catfish and
      the aquaculture feeds, suggesting these feeds as a major source of pollution to
      the farmed catfish. On the other hand, the PBDE and PCB profiles in the dumpsite
      catfish are clearly different from those of the farmed catfish, revealing their
      exposure to different sources. Risk assessment showed significantly higher intake
      of the contaminants by people who eat catfish cultured near the dumping areas.
      Further investigation regarding fate and occurrence of the contaminants in
      dumping sites is necessary.

PMID- 17022412
TI  - Body mass and caloric value of the ground beetle (Pterostichus oblongopunctatus)
      (Coleoptera, Carabidae) along a gradient of heavy metal pollution.
AB  - At five sites located along a metal-pollution gradient in southern Poland, we
      collected, during the spring and summer of 2000, more than 1,200 individuals of
      the ground beetle (Pterostichus oblongopunctatus) to examine the relationship
      between pollution level and body mass. Animals from one additional sampling in
      May 2001 were used to measure body caloric value to verify whether metal
      pollution has an effect on the energy content of the body. The study sites were
      located in an area with a history of zinc and lead mining and smelting dating
      back to medieval times. Metal concentrations in the humus layer ranged from 200
      to 9,600 mg/kg of zinc, 120 to 1,600 mg/kg of lead, and 3 to 82 mg/kg of cadmium.
      We found a significant increase in body mass with increasing pollution level. The
      beetles from all sites collected near the end of the season were lighter.
      However, no statistically significant trend in body caloric value was detected.
      We suggest that the high metal tolerance of the species, combined with altered
      interspecies competition at the polluted sites, is responsible for the positive
      correlation between soil metal concentration and body mass.

PMID- 17022413
TI  - Effects of exposure to the water-soluble fraction of crude oil on the swimming
      performance and the metabolic and ionic recovery postexercise in Pacific herring
      (Clupea pallasi).
AB  - The swimming performance and recovery from exercise were determined in juvenile
      Pacific herring (Clupea pallasi) following exposure to the water-soluble fraction
      (WSF) of North Slope crude oil for more than eight weeks. Total polycyclic
      aromatic hydrocarbon concentrations (mean +/- standard error) at the beginning of
      exposures were as follows: control, 0.2 +/- 0.1 microg/L; low, 9.6 +/- 2.5
      microg/L; medium, 40.7 +/- 6.9 microg/L; and high, 120.2 +/- 11.4 microg/L.
      Biological availability of hydrocarbons was confirmed by a significant induction
      of hepatic cytochrome P450 content and ethoxyresorufin-O-deethylase activity.
      Critical swimming speed (Ucrit) was significantly reduced in fish exposed to the
      highest concentration of WSF for 96 h (11% +/- 3.7% reduction) and at the two
      highest concentrations at four weeks (16% +/- 3.6% and 29% +/- 5.4% reductions)
      and eight weeks (11% +/- 3.8% and 40% +/- 5.7% reductions). Mortality occurred in
      all groups 24 h following Ucrit swim trials, with significantly higher
      mortalities observed in fish exposed to WSF in a concentration- and time
      dependent manner (maximum mortality of 72.2% +/- 5.5% in the eight-week, high
      exposure group). Burst swimming alone resulted in increased plasma cortisol,
      lactate, Na+, and Cl- concentrations and decreased muscle glycogen levels that
      returned to baseline values by 24 h. An interpretation of the effect of WSF
      exposure on postexercise metabolic recovery was complicated by pre-exercise
      alterations in several parameters. The time courses and magnitudes of several key
      postexercise parameters, including plasma cortisol, lactate, and muscle glycogen,
      were significantly altered by exposure to WSE The present study clearly shows
      that hydrocarbon exposure can reduce the swimming ability of fish and their
      ability to recover from exhaustive exercise.

PMID- 17022414
TI  - Hexavalent chromium reduces larval growth and alters gene expression in mummichog
      (Fundulus heteroclitus).
AB  - Hexavalent chromium [Cr(VI)] is a common bioavailable metal ion that causes
      oxidative stress, DNA adducts, and perturbs gene expression. Changes in gene
      expression are useful biomarkers of toxicant exposure that provide information
      about an organism's health, adaptability, and toxicant-specific effects.
      Therefore, we developed a cDNA array for the estuarine sentinel species mummichog
      (Fundulus heteroclitus). Mummichog larvae were exposed to concentrations ranging
      from 0 to 24 mg/L (462 microM) of Cr(VI) for 30 d, and growth was measured to
      determine the no-observable-effect concentration (1.5 mg/L) and the lowest
      observable-effect concentration (3 mg/L). Body burdens from Cr(VI)-exposed fish
      showed a dose-dependent increase and were inversely correlated to body weight.
      Mummichog larvae exposed to Cr(VI) differentially expressed 16 genes in a dose
      dependent manner, including GLUT-2, L-FABP, ATPase synthase 8, type II keratin,
      TBT-binding protein, and complement component C3-2. Many of these genes are
      involved in energy metabolism or growth, which is consistent with the reduced
      growth observed. In subsequent experiments, adults were exposed to Cr(VI) for 7 d
      at 0, 1.5, or 3 mg/L, because adult mummichog are used in monitoring Superfund
      sites. Hexavalent chromium altered the expression of 10 genes in adult liver,
      including HGFA, H-FABP, and complement component C3-2. Many of these genes also
      are involved in energy metabolism. The mummichog arrays provide a potential
      mechanism for the effects of Cr(VI) on growth. We anticipate using these arrays
      and the data they provide to monitor effects at polluted sites, to assess the
      bioavailability of chromium at these sites, and to investigate the efficacy of
      remediation in chromium-polluted estuaries.

PMID- 17022415
TI  - Vitellogenin 1 mRNA as an early molecular biomarker for endocrine disruption in
      developing zebrafish (Danio rerio).
AB  - Contemporary ecotoxicology is faced with the challenge of mechanistic
      understanding, a prerequisite for advanced risk assessment where acute toxicity
      is not the main issue. To achieve this, bioassay systems that are fast and
      biologically integrating and that detect a multitude of effects on a molecular
      level are needed. We present here the concept of such a novel test system that is
      built on the Danio rerio teratogenicity (DarT) assay but is extended in time and
      is based on testing molecular effects in the subacute toxicity range, named
      MolDarT. As proof of principle, we show the use of measuring vitellogenin 1 gene
      (vtg1) mRNA levels as a molecular marker for estrogenicity in developing
      zebrafish, a first module of MolDarT. Fertilized zebrafish eggs were exposed to
      100, 1,000, and 2,000 ng/L (6.75 nM) 17 alpha-ethinylestradiol (EE2), and total
      RNA was isolated every 24 h up to 120 h postfertilization (hpf). Abundance of
      vtg1 mRNA was detected using reverse transcription real-time polymerase chain
      reaction and normalized to beta-actin mRNA abundance. Between 48 and 120 hpf,
      beta-actin mRNA levels were constant, making this gene a suitable reference gene
      for normalization. A significant up-regulation of vtg1 expression was detected at
      48 hpf for 1,000 and 2,000 ng/L EE2. At 72, 96, and 120 hpf, vtg1 was
      significantly induced for all EE2 concentrations. Expression of vtg1 was also
      measured in unexposed developing zebrafish. At 24 hpf and at all later time
      points, zebrafish embryos contained vtg1 transcripts. These findings show that
      vtg1 is regularly expressed in developing zebrafish and that it is inducible by
      EE2. We propose the use of vtg1 as molecular target for estrogenicity in the
      MolDarT.

PMID- 17022416
TI  - Comparison of response to 17 beta-estradiol and 17 beta-trenbolone among three
      small fish species.
AB  - Three small fish species, medaka (Oryzias latipes), fathead minnow (Pimephales
      promelas), and zebrafish (Danio rerio), were exposed to an estrogen, 17 beta
      estradiol (E2), and an androgen, 17 beta-trenbolone (TB), for 21 d under flow
      through conditions to compare the susceptibility among these three small fish
      species to the substances. Effects on gross morphology, including secondary sex
      characteristics and gonadosomatic index, as well as on blood or liver
      vitellogenin (VTG) levels were assessed. In E2 exposures, significant increases
      in estrogenic activity were observed in both sexes of all three fish species. The
      lowest-observed-effect concentrations (LOECs) of E2 for VTG induction in males of
      medaka, fathead minnow, and zebrafish were less than or equal to 8.94, 28.6, and
      85.9 ng/L, respectively. In TB exposures, we observed masculinization of
      secondary sex characteristics in females as a result of the androgenic activity
      of TB in medaka with a LOEC of 365 ng/L and in fathead minnow with a LOEC of 401
      ng/ L. We also found VTG reduction in females of all three fish species. These
      results suggest that the susceptibility of medaka to estrogenic chemicals may be
      higher than those of fathead minnow and zebrafish and that the susceptibility of
      medaka to androgenic chemicals may be almost equal to that of fathead minnow in
      the 21-d fish assay.

PMID- 17022417
TI  - Stimulation of reproductive growth in rainbow trout (Oncorhynchus mykiss)
      following exposure to treated sewage effluent.
AB  - Rainbow trout (Oncorhynchus mykiss) were exposed to 1.5 and 15% v/v secondary
      treated sewage effluent for 32 weeks in flow-through mesocosms. The exposure
      encompassed the full period of reproductive development for rainbow trout. Trout
      did not show any evidence of a dose-dependent change in growth. Fish exposed to
      15% effluent were the only group to show mortality (5%) over the duration of the
      experiment. Trout at the highest effluent concentration had significantly higher
      liver size than reference water fish. Both male and female trout in the 15%
      exposure group also exhibited significantly higher gonad weight than the
      reference group. In female trout, this gonad size increase could be explained by
      higher egg numbers. Female and male trout both displayed a significant increase
      in plasma 17 beta-estradiol levels after exposure to 15% effluent, while neither
      sex had dose-dependent differences in plasma testosterone. Male trout displayed
      elevated vitellogenin levels and reduced plasma 11-ketotestosterone concentration
      after exposure to 15% effluent. Chemical examination of steroidal compounds,
      including both estrogens and androgens, in the wastewater revealed that only
      estrone was detectable at a mean concentration of 4.5 ng/L. It is assumed that
      the effects observed in trout exposed to 15% effluent were consistent with
      stimulation of reproductive development due to very low levels of estrogens.
      Overall, long-term exposure to treated sewage effluent containing low levels of
      estrogen did not have significant negative implications for reproductive
      development in rainbow trout.

PMID- 17022418
TI  - Use of the oligochaete, Lumbricuilus variegatus, as a prey organism for toxicant
      exposure of fish through the diet.
AB  - The oligochaete, Lumbriculus variegatus, has several characteristics that make it
      desirable as a prey organism for conducting dietary exposure studies with fish.
      We conducted 21- and 30-d experiments with young fathead minnows (Pimephales
      promelas) and rainbow trout (Oncorhynchus mykiss), respectively, to determine
      whether a diet consisting solely of L. variegatus would support normal growth and
      to compare performance with standard diets (Artemia nauplii, frozen brine shrimp,
      or trout chow). All diets were readily accepted, and fish survived and grew well.
      Food conversion in both fathead minnows and rainbow trout was as high as or
      higher for the oligochaete diet compared with others, although this comparison is
      influenced by differences in ration, ingestion rate, or both. The oligochaete
      diet had gross nutritional analysis similar to the other diets, and meets fish
      nutrition guidelines for protein and essential amino acids. Methodologies and
      practical considerations for successfully using oligochaetes as an experimental
      diet are discussed. Considering their ready acceptance by fish, their apparent
      nutritional sufficiency, the ease of culturing large numbers, and the ease with
      which they can be loaded with exogenous chemicals, we believe that L. variegatus
      represents an excellent choice of exposure vector for exposing fish to toxicants
      via the diet.

PMID- 17022419
TI  - Toxicity of glyphosate as Glypro and LI700 to red-eared slider (trachemys scripta
      elegans) embryos and early hatchlings.
AB  - More than 8.2 billion ha of cropland, gardens, and forests are treated with the
      herbicide glyphosate each year. Whereas the toxicity of glyphosate and associated
      adjuvants has been measured in other vertebrates, few, if any, studies have
      looked at their effects in reptiles. In some instances, management of turtle
      habitat requires control of successional stages through application of
      herbicides. Adults and juvenile turtles may be exposed directly, whereas embryos
      may contact the chemicals through the soil. In the present study, we exposed eggs
      of red-eared sliders (Trachemys scripta elegans) to single applications of
      herbicide ranging from 0 to 11,206 ppm wet weight of glyphosate in Glypro and 0
      to 678 ppm of the surfactant, LI700. Hatching success at the highest
      concentration was significantly lower (73%) than in other treatments (80-100%).
      At hatch, turtles at the highest concentration weighed less than those at other
      concentrations. During a 14-d holding period, we observed dose-response
      relationships in the ability of hatchlings to right themselves when turned on
      their backs. At the end of the holding period, hatchlings at the highest dose
      level were still lighter, and somatic indices were lower, than those in other
      treatments. Genetic damage, as measured by flow cytometry, increased with
      treatment concentration except for the highest dose. We conclude that because of
      the high concentrations needed to produce effects and the protection offered by
      several centimeters of soil or sediment, glyphosate with LI700 poses low levels
      of risk to red-eared slider embryos under normal field operations with regards to
      the endpoints measured in the present study. Carelessness in handling glyphosate
      or failure to follow label directions may produce adverse effects. There also is
      a risk that the health of turtle embryos may be affected in ways not measured in
      the present study.

PMID- 17022420
TI  - Influences of aging on the bioavailability of sediment-bound Cd and Zn to deposit
      feeding sipunculans and soldier crabs.
AB  - The radiotracer technique was used to assess the influences of sediment-metal
      contact time or aging (up to two years) on the bioavailability and geochemical
      speciation of Cd and Zn in sediments. Bioavailability was quantified by measuring
      the assimilation efficiency of metals in two deposit-feeding invertebrates
      (sipunculans and soldier crabs) and the extraction by the sipunculans' gut
      juices. Sediment aging generally did not significantly affect the Cd speciation
      in the sediments, Cd assimilation, and Cd extraction. In contrast, sediment aging
      significantly affected the Zn distribution in different geochemical phases and
      the Zn bioavailability. With increasing aging, the Zn distributed in the
      carbonate phase decreased, whereas that in the reducible phase increased.
      Accordingly, the Zn gut-juice extraction decreased significantly. Two years of
      aging were not sufficient for Zn to be associated with the organic and residual
      phases. A significant positive correlation was found between Cd gut-juice
      extraction and assimilation efficiency. Gut-juice extraction of Cd and Zn
      generally increased with metal distribution in the exchangeable and carbonate
      phases but decreased with that in the reducible phase. Our results suggest that
      different metals are influenced by sediment aging differently and that
      geochemical speciation analysis is useful in studying the bioavailability of
      sediment-bound metals. This study may have implications for designing sediment
      toxicity tests using spiking techniques and for understanding the fates of
      anthropogenically derived metals in sediments.

PMID- 17022421
TI  - Effects of hardness and alkalinity in culture and test waters on reproduction of
      Ceriodaphnia dubia.
AB  - Ceriodaphnia dubia were cultured in four reconstituted water formulations with
      hardness and alkalinity concentrations ranging from soft to the moderately hard
      water that is required by whole-effluent toxicity (WET) testing methods for
      culturing test organisms. The effects of these culture formulations alone and in
      combination with two levels of Cl-, SO4(2-), and HCO3- on reproduction of C.
      dubia were evaluated with the standard three-brood test. Reproduction was
      significantly reduced when test waters had lower hardness than culture waters.
      However, reproduction was not significantly different when animals cultured in
      low-hardness waters were exposed to moderately hard waters. The hardness of the
      culture water did not significantly affect the sensitivity of C. dubia to the
      three anions. Conversely, increased hardness in test waters significantly reduced
      the toxicities of Cl- and SO4(2-), with HCO3- toxicity following the same
      pattern. Alkalinity exhibited no consistent effect on Cl- and SO4(2-) toxicity.
      The physiological stress of placing animals cultured in moderately hard water
      into softer test waters might contribute to marginal failures of otherwise
      nontoxic effluents. The standard WET protocol should be revised to allow the
      culture of C. dubia under lower hardness conditions to better represent local
      surface water chemistries.

PMID- 17022422
TI  - Embryonic exposure to o,p'-DDT causes eggshell thinning and altered shell gland
      carbonic anhydrase expression in the domestic hen.
AB  - The mechanism for contaminant-induced eggshell thinning in wild birds remains to
      be clarified. It is generally assumed, however, that it results from exposure of
      the adult laying female. We have reported that embryonic exposure to the
      synthetic estrogen ethynylestradiol (EE2) results in eggshell thinning in the
      domestic hen. The objective of this study was to investigate whether eggshell
      thinning can be induced following in ovo exposure to a bioaccumulating estrogenic
      environmental contaminant, o,p'-DDT. Ethynylestradiol was used as a positive
      control. Domestic hens exposed in ovo to o,p'-DDT (37 or 75 microg/g egg) or EE2
      (60 ng/g egg) laid eggs with thinner shells than the control birds. The hens from
      these exposure groups also had a significantly reduced frequency of shell gland
      capillaries with carbonic anhydrase (CA) activity, a key enzyme in eggshell
      formation. The decreased number of capillaries with CA activity suggests that a
      developmentally induced disruption of CA expression in the shell gland was
      involved in the eggshell thinning found in this study. Egg laying was not
      affected in hens exposed embryonically to 37 or 75 microg o,p'-DDT/g egg, whereas
      it was inhibited in hens exposed to higher doses. Decreased lengths of the left
      oviduct and its infundibulum were seen after embryonic treatment with o,p'-DDT or
      EE2. In addition, o,p'-DDT exposure resulted in right oviduct retention. The
      results support our hypothesis that eggshell thinning in avian wildlife can
      result from a functional malformation in the shell gland, induced by embryonic
      exposure to estrogenic substances.

PMID- 17022424
TI  - Environmental temperature changes uptake rate and bioconcentration factors of
      bisphenol a in tadpoles of Rana temporaria.
AB  - Toxicokinetics of radiolabeled (14C) bisphenol A was studied in the common frog
      (Rana temporaria) at two experimental temperatures (7 and 19 degrees C). The
      growth rate of the tadpoles during the 96-h experiment was very slow at 7 degrees
      C, but the weight of tadpoles almost tripled at 19 degrees C. At all tested
      exposure concentrations (0.2, 1.5, 10, and 100 microg/L), conditional uptake rate
      constants (ku) were 69 to 82%, and elimination rates (ke) 79 to 90% lower, at 7
      degrees C than at 19 degrees C. On the contrary, bioconcentration factors (BCFs)
      were higher at 7 degrees C than at 19 degrees C. Total accumulated bisphenol A
      per individual was higher at 19 degrees C, which is in agreement with higher k,
      at 19 degrees C. Exposure concentrations did not have any constant effect on BCFs
      at the two temperatures. The results of the current experiment suggest that
      higher temperature increases uptake and total amount of chemical in frog tadpoles
      but does not necessarily lead to higher BCFs. High temperature may have increased
      the growth rate more than the uptake rate, resulting in a net dilution of
      bisphenol A in tadpole tissues. The observed difference in BCFs also could be a
      result of temperature-induced changes in allometric relationships (increased
      surface area to volume ratio) and/or more effective elimination in more developed
      tadpoles at high temperature.

PMID- 17022423
TI  - Evaluation of genotoxic effects of heavy metals and arsenic in wild nestling
      white storks (Ciconia ciconia) and black kites (Milvus migrans) from southwestern
      Spain after a mining accident.
AB  - Studies of birds from Donana (southwestern Spain) after the Aznalcollar mining
      accident (April 1998) have reported high levels of genetic damage when compared
      to conspecifics from reference areas. However, potential relationships between
      DNA damage and metal pollution have not yet been reported. The aim of the present
      study was to investigate the current levels of Zn, Pb, As, Cu, and Cd and to
      determine if they were associated with the genetic damage observed in free
      living, nestling white storks (Ciconia ciconia) and black kites (Milvus migrans)
      born in the Donana area after the mining spill. Blood concentrations of heavy
      metals and of As were quantified and DNA damage (comet assay) was determined in
      258 storks and 132 kites monitored during a four-year period (1999-2002).
      Correlations between these elements and genetic damage varied between species and
      throughout years within species. Some elements did not show any relationship with
      DNA damage (e.g., Pb), whereas others had a significant correlation (e.g., As in
      storks, and Cu and Cd in kites) or only marginal statistical effects (e.g., Zn
      and Cd in storks, and As in kites) in some years but not in others. These results
      suggest that nestling white storks and black kites were affected, in part, by the
      elements studied, but they alone do not satisfactorily explain the observed DNA
      damage. Moreover, our results show that species-specific differences should be
      carefully considered when planning schemes for pollution monitoring, and
      highlight the need for including the temporal scale into the study of the
      pollutants effects in the wild.

PMID- 17022425
TI  - Changes in juvenile coho salmon electro-olfactogram during and after short-term
      exposure to current-use pesticides.
AB  - For anadromous salmonids, olfaction is a critical sense, enabling return
      migration. In recent years, several pesticides have been identified that
      interfere with salmonid olfaction at concentrations in the microg/L range; thus,
      they may pose a risk to species longevity. In the present study, we investigated
      the acute effects of five agricultural pesticides on juvenile coho salmon
      (Oncorhynchus kisutch) olfaction using the electro-olfactogram (EOG), a measure
      of odorant-evoked field potentials. Electro-olfactogram responses to the odorant
      L-serine were measured during and following a 30-min exposure of the left
      olfactory rosette to chlorothalonil, endosulfan, glyphosate acid, iodocarb
      (IPBC), trifluralin, and 2,4-dichlorophenoxyacetic acid. With the relatively
      insoluble pesticides endosulfan and trifluralin, decreases in EOG amplitude were
      only apparent at relatively high concentrations (100 and 300 microg/L,
      respectively) following 20 min of exposure and were absent for chlorothalonil (1
      mg/L). With the water-soluble herbicide glyphosate, significant EOG reductions
      occurred within 10 min of exposure to 1 mg/L and more rapidly with higher
      concentrations. Recovery of EOG post-glyphosate exposure was concentration
      dependent, and complete recovery was not observed with some concentrations at 60
      min postexposure. Dichlorophenoxyacetic acid only affected EOG at high
      concentration (100 mg/L), where it eliminated EOG within 2 min of exposure. With
      IPBC, EOG was decreased at 25 min of exposure to 1 microg/L; higher
      concentrations caused decreases to occur more rapidly. Excluding IPBC and
      glyphosate, all EOG reductions occurred at concentrations greater than the
      current Canadian water-quality guidelines and reported 96-h lethality values. Our
      results show that olfactory neurons can be impaired rapidly by some current-use
      pesticides, even at exposures in the low-microg/L range.

PMID- 17022426
TI  - Affordable medications in India.

PMID- 17022427
TI  - Precertification, denials and appeals.

PMID- 17022428
TI  - Coding & documentation.

PMID- 17022429
TI  - ICD-9 changes: the new codes are here.

PMID- 17022430
TI  - In search of a super superbill.

PMID- 17022431
TI  - Providing consistent care with standardized admission orders.

PMID- 17022432
TI  - The FPM encounter forms collection: 'paper automation' of your progress.

PMID- 17022433
TI  - Improving communication with older patients: tips from the literature.

PMID- 17022434
TI  - Why I never had an Atari video game system.

PMID- 17022435
TI  - Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent
      induced encephalopathy.
AB  - In the present study, we investigate whether genetic polymorphism in enzymes
      involved in the metabolism of organic solvents influences susceptibility to
      chronic solvent encephalopathy (CSE), which is one of the major effects of long
      term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1,
      CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male
      CSE patients (N=97) and controls (N=214). The selection of the patients was based
      on a standard diagnostic protocol, including interviews, neuropsychological tests
      and questionnaires directed to somatic, cognitive and mood symptoms and exposure,
      in combination with well-defined decision rules. As controls, healthy workers of
      similar socio-economic background, without memory problems and with no known
      exposure to organic solvents, were included in the study. Comparing patients and
      controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR:
      5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17
      0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele
      had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that
      genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing
      CSE.

PMID- 17022436
TI  - Evaluation of toxicity of methyl tert-butyl ether (MTBE) on mouse spermatogenic
      cells in vitro.
AB  - As a synthetic organic chemical, methyl tert-butyl ether (MTBE) is the most
      common fuel oxygenate. The increasing use of MTBE has raised concern over its
      safety. Previous studies in vivo revealed that MTBE could alter the male
      reproduction system. Therefore, the current experiments were designed to evaluate
      whether isolated mice spermatogenic cells in vitro were sensitive to exposure to
      MTBE at environmental levels, and to evaluate whether spermatogenic cells had
      undergone changes in morphologic, activity and viability parameters after
      exposure to MTBE. Spermatogenic cells in vitro were incubated with medium alone
      (control), 100 ppb, 10 ppm, 1000 ppm, 3000 ppm MTBE, respectively, for 6, 12, 18
      h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo liumbromide) assay,
      staining with fluorescein diacetate (FDA) and propidium iodide (PI), and flow
      cytometric analyses were used to assess MTBE toxicity on cells and DNA. The
      results showed that there were no significant differences between control and
      treatments of < or = 1000 ppm MTBE at the same time point. Although 3000 ppm MTBE
      could exert toxic effects directly on spermatogenic cells, environmental levels
      of MTBE did not exert toxic effects on cultured spermatogenic cells.

PMID- 17022437
TI  - Toxicological assessment of industrial solvents using human cell bioassays:
      assessment of short-term cytotoxicity and long-term genotoxicity potential.
AB  - There is an increasing demand for simple toxicological screening methods to
      assess the human health risk associated with exposure to environmental toxicants.
      Such screening tools should allow for risk evaluation in terms of both short
      term/acute toxicity and longer-term genetic damage, which may lead to
      mutagenicity and carcinogenicity. We employed a battery of human cell bioassays
      using the human hepatoma cell-line, HepG2, to assess the cytotoxic and genotoxic
      potential of environmental pollutants. Here, we demonstrate direct application of
      these human cell bioassays to the toxicological assessment of a number of
      industrial solvents that are in common use worldwide. HepG2 cells were exposed to
      various solvents at concentrations ranging from 25 to 500 ppm. The cells were
      then analysed using specific protocols for four different adverse effects: cell
      death/acute cytotoxicity using a neutral red uptake assay, altered enzyme
      function (often an indicator of cell stress) using the ethoxyresorufin O
      deethylase (EROD) bioassay, DNA single strand breaks (SSB), and DNA repair
      induction, which evaluates mutagenic activity. Using the positive controls,
      linear dose-response curves were achieved for all four bioassays. The high
      sensitivity of the tests allowed for environmentally meaningful assessments, and
      precision studies showed excellent reproducibility for all four bioassays.
      Comparing the results of the four bioassays on each of 16 industrial solvents
      allowed for ranking of the anticipated relative human toxicity of these solvents,
      which were comparable with data from standard toxicity tests and human
      occupational data. Overall, the study clearly supports the application of the
      HepG2 cell bioassay system for rapid toxicological screening of many candidate
      toxicants for both short- and long-term toxicity potential.

PMID- 17022438
TI  - Health benefits of herbs and spices: the past, the present, the future.
AB  - Herbs and spices have a traditional history of use, with strong roles in cultural
      heritage, and in the appreciation of food and its links to health. Demonstrating
      the benefits of foods by scientific means remains a challenge, particularly when
      compared with standards applied for assessing pharmaceutical agents.
      Pharmaceuticals are small-molecular-weight compounds consumed in a purified and
      concentrated form. Food is eaten in combinations, in relatively large, unmeasured
      quantities under highly socialised conditions. The real challenge lies not in
      proving whether foods, such as herbs and spices, have health benefits, but in
      defining what these benefits are and developing the methods to expose them by
      scientific means. CULTURAL ASPECTS: The place of herbs and spices in the diet
      needs to be considered in reviewing health benefits. This includes definitions of
      the food category and the way in which benefits might be viewed, and therefore
      researched. Research may focus on identifying bioactive substances in herbs and
      spices, or on their properties as a whole food, and/or be set in the context of a
      dietary cuisine. THE ROLE OF HERBS AND SPICES IN HEALTH: The antioxidant
      properties of herbs and spices are of particular interest in view of the impact
      of oxidative modification of low-density lipoprotein cholesterol in the
      development of atherosclerosis. There is level III-3 evidence (National Health
      and Medical Research Council [NHMRC] levels of evidence) that consuming a half to
      one clove of garlic (or equivalent) daily may have a cholesterol-lowering effect
      of up to 9%. There is level III-1 evidence that 7.2 g of aged garlic extract has
      been associated with anticlotting (in-vivo studies), as well as modest reductions
      in blood pressure (an approximate 5.5% decrease in systolic blood pressure). A
      range of bioactive compounds in herbs and spices have been studied for
      anticarcinogenic properties in animals, but the challenge lies in integrating
      this knowledge to ascertain whether any effects can be observed in humans, and
      within defined cuisines. Research on the effects of herbs and spices on mental
      health should distinguish between cognitive decline associated with ageing and
      the acute effects of psychological and cognitive function. There is level I and
      II evidence for the effect of some herbal supplements on psychological and
      cognitive function. There is very limited scientific evidence for the effects of
      herbs and spices on type 2 diabetes mellitus, with the best evidence being
      available for the effect of ginseng on glycaemia, albeit based on four studies.
      More research is required, particularly examining the effects of chronic
      consumption patterns. With increasing interest in alternatives to non-steroidal
      anti-inflammatory agents in the management of chronic inflammation, research is
      emerging on the use of food extracts. There is level II evidence for the use of
      ginger in ameliorating arthritic knee pain; however, the improvement is modest
      and the efficacy of ginger treatment is ranked below that of ibuprofen. More
      definitive research is required. PUBLIC HEALTH AND DIETARY IMPLICATIONS:
      Recommendations for intakes of food in the Australian guide to healthy eating do
      not yet include suggested intakes of herbs and spices. Future consideration
      should be given to including more explicit recommendations about their place in a
      healthy diet. In addition to delivering antioxidant and other properties, herbs
      and spices can be used in recipes to partially or wholly replace less desirable
      ingredients such as salt, sugar and added saturated fat in, for example,
      marinades and dressings, stir-fry dishes, casseroles, soups, curries and
      Mediterranean-style cooking. Vegetable dishes and vegetarian options may be more
      appetising when prepared with herbs and spices. FUTURE DIRECTIONS: As several
      metabolic diseases and age-related degenerative disorders are closely associated
      with oxidative processes in the body, the use of herbs and spices as a source of
      antioxidants to combat oxidation warrants further attention. Immediate studies
      should focus on validating the antioxidant capacity of herbs and spices after
      harvest, as well as testing their effects on markers of oxidation. This will work
      in parallel with clinical trials that are aiming to establish antioxidants as
      mediators of disease prevention. From a dietary perspective, the functionality of
      herbs and spices will be exposed through consideration of their properties as
      foods. As with most foods, the real benefits of including them in the diet are
      likely to emerge with a better understanding of the attributes of health that are
      best supported by food, and in methodological developments addressing the
      evidence base for their effects. These developments are well underway through
      evidence-based frameworks for substantiating health claims related to foods. At
      present, recommendations are warranted to support the consumption of foods rich
      in bioactive components, such as herbs and spices. With time, we can expect to
      see a greater body of scientific evidence supporting the benefits of herbs and
      spices in the overall maintenance of health and protection from disease.

PMID- 17022439
TI  - [Topology of cleavage in light of the Pierre Curie principle].
AB  - The stages of radial, spiral, and bilateral cleavage, including blastula, are
      considered as polyhedrons and projections of polyhedrons onto a plane: Wenn,
      Schlegel, and Euler projections. The blastula spatial organization is
      characterized by face numerals and Euler characteristics, as well by symmetry
      groups. The classes of equivalence of polyhedrons have been considered: duality
      and eqicomposition. The correspondence between different types of cleavage has
      been established by shift transformation on Schlegel projections and turn on a
      spherical noneuclidean surface. Determination of the prospective significance of
      blastomeres during cleavage was compared with the dichotomous division of the
      general notion in logic. This in view, the Wenn diagram of four figures has been
      reflected onto the sphere surface. Blastula faceting is interpreted as a
      reflection of hereditary information about the prospective significance of
      blastomeres onto a spherical surface. Topologically, the reflection represents a
      transformation of the linear orderliness of information contained in the genome
      into a two-dimensional orderliness of prospective properties on the blastula
      noneuclidean surface. Therefore, the elements of blastula symmetry can be
      considered as self in the sense of Pierre Curie principle.

PMID- 17022440
TI  - [Evolutionary reorganizations of ontogenesis in related species of coenobial
      volvocine algae].
AB  - The evolutionary aspects of ontogenesis in green volvocine algae have been
      considered on the basis of the author's and published data, as well as the
      information on taxonomy, phylogeny, and ecology of this group. Analysis of the
      rate, diurnal rhythm, and light/dark control of cell divisions in various
      species, as well as experiments with the nucleic acid and protein synthesis
      inhibitors made it possible to elucidate cellular mechanisms underlying
      evolutionary rearrangements of asexual development in the genus Volvox.

PMID- 17022441
TI  - [A study of quantitative dynamics of F-actin during oocyte maturation in the
      starfish Asterias amurensis].
AB  - We studied the actin cytoskeleton state in Asterias amurensis oocytes within 30
      min after the 1-methyladenine-induced maturation until the germinal vesicle
      breakdown. The total amount of actin remained unchanged during oocyte maturation.
      In immature oocytes, the major part of actin is not a part of filaments, but in
      the presence of 1-methyladenine massive actin polymerization began already within
      20 min. Electron immunocytochemistry methods demonstrated joint localization of
      actin and alpha-protein in the cytoplasm. They were redistributed from the cortex
      to the cytoplasm in the presence of 1-methyladenine. A possible involvement of
      actin cytoskeleton in transmembrane transduction of the hormonal signal at the
      postreceptor stages is discussed.

PMID- 17022442
TI  - [Role of seasonal factors in pre- and postnatal ontogenesis for etiology of type
      1 diabetes mellitus].
AB  - Type 1 diabetes mellitus is a chronic disease characterized by autoimmune
      degradation of insulin-producing beta-cells. It was shown in a number of
      epidemiological studies of seasonality of birth in children with type 1 diabetes
      that the autoimmune process began during fetal and postnatal development. No such
      studies were carried out in the former Soviet Union countries. The aim of the
      present study is to compare the seasonal birth month pattern in patients with
      type 1 diabetes (10780 men and 9337 women) born in 1960-2002 to that in the total
      population of Ukraine (14 785601 men and 13 911370 women) born during the same
      period. Significant differences were found between these two populations: chi
      squared = 103.97, p < 0.0001 and 135.17, p < 0.0001 in men and women,
      respectively. The results of cosinor analysis showed similar sinusoidal birth
      patterns of patients with type 1 diabetes in all sub-groups, irrespective of the
      age of clinical disease expression: 0-9, 10-19, or 20-29 years. In all cases, the
      highest and lowest predispositions to type 1 diabetes were inherent in the people
      born in spring and autumn, respectively. We propose that seasonal differences in
      the birth pattern in the two above populations could be due to long-term
      programming of glucose-insulin metabolism determined by the effect of certain
      seasonal factors during early ontogenesis.

PMID- 17022443
TI  - [Dynamics of apoptosis and proliferation in the rat thymus and spleen during
      perinatal development].
AB  - The levels of spontaneous apoptosis and proliferation of the rat thymic and
      spleen cells, as well as their regulation by the hypothalamo-hypophysial system
      were studied during perinatal development. The apoptotic and proliferating cells
      in the thymus and spleen were assayed using flow cytometry with the DNA-specific
      dye propidium iodide. The level of apoptosis in the thymus reached 25% on day 18
      of embryogenesis (E 18) and decreased to 5% thereafter. In the spleen, the level
      of apoptosis gradually increased from 15 to 37% during the period of E18 to day
      30 of postnatal development (P30). The level of dividing cells in the thymus was
      20-25% at all developmental stages studied. In the spleen, it was at a maximum on
      E18 (32%) and decreased almost twice on E21 (17%). On P7, the amount of
      proliferating cells again increased to 22% and then gradually decreased to 7% by
      P30. The surgical ablation of hypothalamus in utero on E18 did not affect cell
      apoptosis or proliferation in the thymus and spleen. The surgical ablation of
      both hypothalamus and pituitary led a twofold decrease of the level of apoptosis
      in the spleen and insignificant increase of the level of proliferation in the
      thymus. Thus, the numbers of cells in the embryonic thymus is regulated not only
      by the thymus itself, but also by the hypothalamo-hypophysial system. The
      programmed cell death in the embryonic spleen appears to be regulated by the
      hypothalamo-hypophysial system as well.

PMID- 17022444
TI  - [Cultivation and transplantation of boar type A spermatogonia].
AB  - A cell population enriched with type A spermatogonia has been isolated from the
      boar testes. Cell types occurring during isolation were morphologically
      characterized, factors maintaining the cultured spermatogonia in the
      undifferentiated state were studied, and these cells were transferred to sterile
      recipients preliminarily treated with busulfan. The cells of spermatogenic
      epithelium cultivated in vitro for 24 h were used for transfer experiments. The
      transfer efficiency was estimated within 27 and 29 days according to the
      histological picture of the testes and the isolated cultures. Spermatogenic cells
      at various developmental stages and a few Sertoli ells and spermatozoa were found
      on sections and in cell suspensions. Sperm samples could be taken from recipient
      boars within nine months after the transfer. Microsatellite analysis of DNA
      showed the endogenous pattern of spermatogenesis. Thus, it was shown that
      spermatogenic donor cells can restore and maintain spermatogenesis of a recipient
      for at least 30 days. However, the donor cells were fully forced by the recipient
      reserve cells, type A0 spermatogonia, within eight to nine months.

PMID- 17022445
TI  - [Conference "Biology of Stem Cells: Fundamental Aspects"].

PMID- 17022446
TI  - [Aerobic processing of the organic wastes into compost].
AB  - The review is devoted to modern achievement in area of the aerobic processing of
      the organic wastes in compost for improvement of an ecological condition of the
      environment and purposeful use at intensification of an agriculture. The methods
      of reception and characteristic of products of microbiological transformation
      household, agricultural and industrial wastes are considered.

PMID- 17022447
TI  - [Modification of a catalase by glutaraldehyde].
AB  - Polycondensation of a catalase (EC 1.11.1.6) with glutaraldehyde in order to
      stabilize the quaternary structure of an enzyme, maintain its activity, and
      protect it from thermal denaturation was studied. Synthesis showed a
      superequivalent utilization of the aldehyde groups relative to the catalase amine
      groups, as a result of the formation of glutaraldehyde oligomers linked to the
      enzyme.

PMID- 17022448
TI  - [Dependence of equilibrium and kinetic parameters of erythromycin: a sorption on
      the structural characteristics of the biosorbent].
AB  - The use of special synthetic sorbents with surface carboxyl groups allowed us to
      increase fourfold the effective diffusion coefficient for erythromycin. The
      maximum sorption capacity for the antibiotic exceeded twofold that observed in
      experiments with a macroporous sulfocation exchanger MN-500. The sorption of the
      antibiotic was completely reversible upon treatment with a combined eluant that
      competitively interacts with the sorbent and does not impair the structural
      characteristics of erythromycin.

PMID- 17022449
TI  - [Carbohydrate specificity of lectins from luminescent bacteria].
AB  - The presence of lectins on a cell surface was demonstrated for 70 cultures of
      luminescent bacteria using hemagglutination reactions. It was shown that
      hemagglutination of luminescent bacteria is inhibited by glucose, maltose,
      fructose, mannose, and N-acetyl-D-glucosamine. The differences in the inhibition
      of hemagglutination of luminescent and nonluminescent (spontaneous mutants)
      symbiotic cultures by N-acetyl-D-galactosamine were revealed. The fact that N
      acetyl-D-galactosamine inhibits hemagglutination of the luminescent symbiotic
      bacteria but does not inhibit hemagglutination of the symbiotic cultures lacking
      luminescence suggests that lectins with N-acetyl-D-galactosamine specificity are
      possibly involved in the formation and functioning of the symbiosis of
      luminescent bacteria with marine animals possessing luminous organs.

PMID- 17022450
TI  - Physiological changes induced in four bacterial strains following oxidative
      stress.
AB  - In order to study the behaviour and resistance of bacteria under extreme
      conditions, physiological changes associated with oxidative stress were monitored
      using flow cytometry. The study was conducted to assess the maintenance of
      membrane integrity and potential as well as the esterase activity, the
      intracellular pH and the production of superoxide anions in four bacterial
      strains (Ralstonia metallidurans, Escherichia coli, Shewanella oneidensis and
      Deinococcus radiodurans). The strains were chosen for their potential usefulness
      in bioremediation. Suspensions of R. metallidurans, E. coli, S. oneidensis and D.
      radiodurans were submitted to 1 h oxidative stress (H2O2 at various
      concentrations from 0 to 880 mM). Cell membrane permeability (propidium iodide)
      and potential (rhodamine-123, 3,3'-dihexyloxacarbocyanine iodide), intracellular
      esterase activity (fluorescein diacetate), intracellular reactive oxygen species
      concentration (hydroethidine) and intracellular pH (carboxyflurorescein diacetate
      succinimidyl ester (5(6)) were monitored to evaluate the physiological state and
      the overall fitness of individual bacterial cells under oxidative stress. The
      four bacterial strains exhibited varying sensitivities towards H2O2. However, for
      all bacterial strains, some physiological damage could already be observed from
      13.25 mM H2O2 onwards, in particular with regard to their membrane permeability.
      Depending on the bacterial strains, moderate to high physiological damage could
      be observed between 13.25 mM and 220 mM H2O2. Membrane potential, esterase
      activity, intracellular pH and production of superoxide anion production were
      considerably modified at high H2O2 concentrations in all four strains. In
      conclusion, we show that a range of significant physiological alterations occurs
      when bacteria are challenged with H2O2 and fluorescent staining methods coupled
      with flow cytometry are useful for monitoring the changes induced not only by
      oxidative stress but also by other stresses like temperature, radiation,
      pressure, pH, etc....

PMID- 17022451
TI  - [A positive effect of Propionibacterium freudenreichii on the growth of
      Saccharomyces cerevisiae during their cocultivation].
AB  - The growth pattern of Saccharomyces cerevisiae and Propionibacterium
      freudenreichii ssp. shermanii (P. shermanii; propionic acid bacteria, PABs)
      during cocultivation in liquid media depended on the ratio of the cells in the
      inoculum. An increase in the growth rate of S. cerevisiae was observed at a PAB
      to yeast ratio of approximately 3 : 1; higher ratios exerted adverse effects on
      yeast growth. The culture liquid of 18- to 24-h (young) cultures of PABs
      stimulated yeast growth. Although yeast growth-stimulating exometabolites of PABs
      were not high-molecular-weight compounds, they were thermolabile. When present in
      the medium at concentrations of up to 1.5%, the antimicrobial agent sodium
      propionate did not interfere with S. cerevisiae growth; however, it completely
      inhibited the growth of B. subtilis at a concentration of 0.2%.

PMID- 17022452
TI  - Stability study on the nitrile hydratase of Nocardia sp. 108: from resting cell
      to crude enzyme preparation.
AB  - In recent years, nitrile hydratases (NHases) have drawn increasing attentions due
      to their critical roles in organic synthesis. In present paper, extensive
      investigation on the stability and activity of the NHase from Nocardia sp. 108,
      which is succeed in the industrial application in China, were conducted by the
      bioconversion of acrylonitrile to acrylamide in a batch manner. Cultivation study
      demonstrated that biosynthesis of NHase changed significantly with culture time,
      and the optimal NHase biosynthesis phase was 45 h after inoculation with NHase
      activity of 1209.8 U/g of biomass. Stability study indicated that crude enzyme
      preparation both exhibit a good stability when exposed to the pH 7.2 tris-HCl
      buffer at 4 degrees C for 4 h.

PMID- 17022453
TI  - [Effect of argillaceous minerals on the growth of phosphate-mobilizing bacteria
      Bacillus subtilis].
AB  - It was shown that the argillaceous minerals montmorillonite and palygorskite at
      concentrations within 0.2-1.0% considerably accelerate the growth of phosphate
      mobilizing bacteria Bacillus subtilis grown in media with hardly soluble
      Ca3(PO4)2 as the sole source of phosphorus. The most notable effect of these
      minerals was recorded at concentrations within 0.5-1.0%. The effect of
      argillaceous minerals in the colloidal form on bacterial growth was more
      pronounced than that of the powdered ones. An increase in montmorillonite or
      palygorskite concentrations to 2% is accompanied by the inhibition of the growth
      of the phosphate-mobilizing strain. At such concentrations the minerals adsorb
      ca. 22% of the glucose and 11.3% of the phosphate added to the nutrition medium.

PMID- 17022454
TI  - [Catalysis of the biodegradation of unusable medicines by alkanotrophic
      rhodococci].
AB  - Experiments on the biodegradation of unusable medicines containing a phenolic
      hydroxy group by actinobacteria of the genus Rhodococcus were performed. Six
      species and sixty-four strains were tested. It was found that rhodococci could
      degrade paracetamol, and some R. ruber strains showed high levels of its
      degradation. An efficient method for the identification and quantification of
      paracetamol and the products of its conversion (p-aminophenol, pyrocatechol, and
      hydroquinone) immediately in the culture liquid was developed. Conditions for the
      complete biodegradation of paracetamol dosage forms (pills) were optimized. The
      experimental results can be applied for the development of biotechnological
      methods for degrading medicines: faked, rejected, or those that are expired.

PMID- 17022455
TI  - [Improvement of the process of fluorene degradation by Rhodococcus rhodochrous
      strain 172].
AB  - The ability of Rhodococcus rhodochrous strain 172 to consume fluorene as the sole
      source of carbon and energy in a liquid medium was successfully increased by an
      addition of polycapramide fiber to the medium and preliminary adaptation of cells
      on fluorene agar. A combination of these approaches allowed complete degradation
      of fluorene without an accumulation of intermediates.

PMID- 17022456
TI  - [Cooxidation of phenol and 4-aminoantipyrin, catalyzed by polymers and copolymers
      of horseradish root peroxidase and Penicillium funiculosum 46.1 glucose oxidase].
AB  - Polymers and copolymers of horseradish root peroxidase (HRP) and Penicillium
      funiculosum 46.1 glucose oxidase (GO) have been synthesized and their catalytic
      properties have been characterized (free and immobilized forms of each enzyme
      were studied). The cooxidation reaction of phenol and 4-aminoantipyrin (4-AAP),
      performed in an aqueous medium in the presence of equimolar amounts of GO and
      HRP, was characterized by effective K(M) and k(cat) of 0.58 mM and 20.9 s(-1)
      (for phenol), and 14.6 mM and 18.4 s(-1) (glucose), respectively. The catalytic
      efficiency of polymerization products (PPs) of GO (GO-PPs) depended on the extent
      of their aggregation. The combinations GO + HRP-PP and HRP + GO-PP, as well as
      the copolymer HRP*-GO-PP, proved promising as reagents for enzyme-based
      analytical systems. When adsorbed on aluminum hydroxide gels, GO-PPs exhibited
      higher catalytic activity than the non-polymeric enzyme. Maximum retention of GO
      PP activity on the inorganic carrier was observed in the case of GO-PP copolymers
      with an activated HRP. Polymerization of HRP in the presence of a zinc hydroxide
      gel, paralleled by HRP-PP immobilization onto the gel, increased both the
      activity of the enzyme and its operational stability.

PMID- 17022457
TI  - [The effect of thaumatin gene overexpression on the properties of H(+)-ATPase
      from the plasmalemma of potato tuber cells].
AB  - The introduction of the thaumatin gene into potato plants was accompanied by a
      decrease in the activity of H(+)-ATPase in the plasmalemma (PL) of tuber cells.
      When tubers were released from dormancy, the enzyme was activated in the tuber
      cells of both the original and transgenic plants. Experiments performed in vitro
      demonstrated that sensitivities to ambiol (AM) and jasmonic acid (JA) of H(+)
      ATPase in the PL of tubers from the original plants were lower after the release
      from a period of deep dormancy. In preparations from the tubers of transgenic
      plants, the situation was reversed. The differences between the activities of
      H(+)-ATPase in the PL preparations produced from the original and transgenic
      tubers that sprouted under the action of AM and JA were detected. Thus, the
      overexpression of the thaumatin gene in potato plants changed the properties of
      H(+)-ATPase from PL.

PMID- 17022458
TI  - [Increase of the detoxification potential of basidiomycetes by induction of
      laccase biosynthesis].
AB  - The effect of oxidoreductase inducers guaiacol and syringaldazine on the ability
      of Coriolus hirsutus, Coriolopsis fulvocinerea, Cerrena maxima, and cocultivated
      Coriolus hirsutus/Cerrena maxima to degrade atrazine in submerged cultures was
      studied. All the basidiomycetes reduced atrazine concentration with and without
      syringaldazine or guaiacol. The degree of atrazine degradation was higher in
      induced cultures (77-98% vs. 68-94% without induction). Of the four cultures, the
      highest detoxifying potential was observed in Coriolopsis fulvocinerea with and
      without an inducer (98% with guaiacol), and the lowest was in Cerrena maxima.
      Inducers decreased the residual atrazine concentration differently in the
      different cultures. A long-term increase of laccase production was observed in
      both induced and uninduced cultures, whereas the activity of Mn-peroxidase
      decreased. The results indicate that laccase plays a larger role in atrazine
      biodegradation than Mn-peroxidase.

PMID- 17022459
TI  - [Regulatory role of elements in the formation and accumulation of alkaloids in
      Papaver somniferum L. seedlings].
AB  - The effects of 12 elements on the formation and accumulation of isoquinolines
      were studied in opium poppy seedlings (Papaver somniferum L.). Three types of
      concentration dependences of the effects of the elements under study were
      determined. The elements served as activators (Co, Mo, W, Cr, and Cu) or
      inhibitors of these processes (B, Fe, V, Mn, and Ca). The molecular mechanisms of
      action of these regulators are discussed. The optimum concentrations of Co and Mo
      were tested under combined treatment conditions with these elements.

PMID- 17022460
TI  - [Identification of AGR2 protein, a novel potential cancer marker, using
      proteomics technologies].
AB  - A comparative analysis of the proteins in prostate tissues of the patients
      operated for hyperplasia (n = 7) or cancer (n = 5) was performed aiming to search
      for protein diagnostic markers. Differences in several minor proteins were
      detected using two-dimensional electrophoresis according to O'Farrel; among them,
      an additional protein with a molecular weight of 19 kDa and an isoelectric point
      of 9.0 was observed in four of the cancer cases. Mass spectrometry allowed this
      protein to be identified as the androgen-induced secreted protein AGR2. The
      possibility of using AGR2 as a diagnostic marker of prostate cancer is discussed.

PMID- 17022461
TI  - [Accuracy of a real-time polymerase-chain-reaction assay for a quantitative
      estimation of genetically modified sources in food products].
AB  - The accuracy of a real-time polymerase-chain-reaction assay for genetically
      modified sources in food products was determined using two official test systems
      (kits) of primers and samples. These kits were recommended by the Federal Center
      of State Sanitary and Epidemiological Surveillance (Russian Ministry of Health)
      and the European Commission. We used the following three models of thermocyclers:
      iCycler iQ (BioRad, United States), Rotor-Gene 3000 (Corbett Research,
      Australia), and DT-322 (DNA-Technology, Russia). Studies of samples that
      contained 1% genetically modified sources showed that the error of a quantitative
      assay for genetically modified sources in food products corresponds to 20-30% and
      does not depend on the kit type and the thermocycler model used.

PMID- 17022463
TI  - [The Eighth International Seminar presentation of Innovation Research Projects
      "Biotechnology-2005"].

PMID- 17022462
TI  - [Collagenolytic activity in several species of deuteromycetes under various
      storage conditions].
AB  - The ability of deuteromycetes of the genera Penicillium, Aspergillus, and
      Botrytis to retain collagenolytic activity was studied after both 2 and 10 years
      of storage on a Czapek medium under a layer of mineral oil at 4 degrees C, as
      well as in silica gel granules at 20 and -60 degrees C. The enzymatic activity of
      several species, including Botrytis terrestris, Penicillium janthinellum,
      Penicillium chrysogenum, and Penicillium citrinum, was retained under both
      conditions of storage. Aspergillus repens retained enzymatic activity only if
      stored under a layer of mineral oil. The viability of conidia and the
      collagenolytic activity of Botrytis terrestris, P. janthinellum, P. chrysogenum,
      and Penicillium citrinum, maintained on silica gel for 10 years, depended on the
      storage temperature. The viability of the test strains improved after storage on
      a silica gel at -60 degrees C. A strain of Aspergillus repens lost its ability to
      dissolve collagen at various storage temperatures on the silica gel. The index of
      lysis for three strains of Penicillium deuteromycetes (Penicillium janthinellum,
      Penicillium chrysogenum, and Penicillium citrinum) increased after a 10-year
      storage on silica gel at -60 degrees C.

PMID- 17022464
TI  - [Neurobiological studies of gamma-band bioelectrical activity in humans].
AB  - The modem literature data were observed, which dedicated to the study of
      neurobiological studies of gamma-rhythm mechanisms, providing the cognitive
      functions in hymans: state of readiness and attention, providing of sensory
      indentification, perception and memorizations, decision-making, management of
      psychomotor response, emotional and semantic processing of an information. It was
      shown that synchronous gamma-activity is at integrative activity, which in
      deteriorated in pathology of thinking. Literature data were analysed concerning
      ot the changes of gamma-activity (spontaneous, evoked, provoked by
      photostimulation etc.) in a number of neuropsychiatric disorders: epilepsy,
      schizophrenia, Alzheimer's disease, attention deficit hyperactivity disorder,
      stroke etc. as compared with norm. The data observed testify to high significance
      of gamma-activity in the brain functioning.

PMID- 17022465
TI  - [Respiratory function of pharyngeal muscles].
AB  - This article reviews experimental studies of pharyngeal muscles with emphasis on
      m. genioglossus as a major muscle dilating pharynx and discusses neuromuscular
      mechanisms that maintains patency of upper airway. Mechanisms of inspiratory
      activation of genioglossus muscle in comparative with diaphragm are also
      discussed. Experimental data suggesting that upper airway muscles have a
      significant role in compensation of added inspiratory load are presented. It
      allows to regard pharyngeal dilating muscles as accessory muscles of respiration.
      Activation of m. genioglossus (together with others muscles dilating the pharynx)
      decreases airway resistance and thereby facilitates the load compensation
      function of "pumping" muscles. Similar to diaphragm involvement of the pharynx
      dilating muscles in the load compensatory response is resulted from a complex
      integration of several influences originating from mechano- and chemoreceptors.

PMID- 17022466
TI  - [Adaptation of myocardium to ischemia. The early phase of ischemic
      preconditioning].
AB  - It has been systematized modem data on the early phase of ischemic
      preconditioning and cardiac resistance to pathogenic action of ischemia and
      reperfusion. It has been performed an analysis published works on the important
      role of alteration of myocardium energy metabolism in the development of
      adaptation resistance of the heart to ischemia. It has been shown that adenosine,
      bradykinin and opioid peptides and also signalling cascade involved phospholipase
      C and D, protein kinase C, tyrosine kinase and mitochondrial ATP-sensitive
      potassium channel play a key role in the mechanism of cardioprotective action of
      ischemic preconditioning.

PMID- 17022467
TI  - [Estimation and prediction of functional changes in organisms in space flight].
AB  - The article is devoted to theoretical and applied problems of estimation of the
      organism functional state and a level of health. Transitive states between health
      and illness, between norm and a pathology, so-called prenosological states are
      considered. The level of health is determined by adaptable opportunities of an
      organism, a degree of regulatory systems tension and their functional reserve. As
      the basic methodical approach to an estimation of a degree of regulatory systems
      tension the method of heart variability analysis is described. The applied aspect
      of a considered problem is submitted by results of the researches which have been
      carried out in conditions of space flight. Changes of organism functional state
      at different stages of adaptation to conditions of long weightlessness are
      described. The mathematical model of functional states is submitted. Four types
      of the vegetative regulation, differing on the adaptive reactions in conditions
      of space flight are allocated. Results of researches of crew members of the
      International space station are submitted.

PMID- 17022469
TI  - [The report on scientific-organizational activity of Section of physiology of
      Branch of biological science RAS in 2005].

PMID- 17022468
TI  - [Influence of cholinergic and adrenergic agents of the electric activity of the
      brain and the heart under hypoxia].
AB  - Injection of adrenergic and cholinergic agents to animals in the normal
      athmospheric conditions did not tigger drastic changes on the electric activity
      of the brain and heart. Acutehipoxia demands high adaptability from the body. In
      such conditions stimulation of reticular formation and hypothalamus produces
      different changes in the EEG and ECG activity whith injecting adrenergic and
      cholinergic agents. It was determined that cholinergic influence are effective in
      the regulation of electrical brain activity while adrenergics are more important
      for the realization of descending influences of the truncus cerebri vegetative
      centers and are less active in the modulation of the cerebral cortex activity.

PMID- 17022470
TI  - [Mikhail Nikolaevich Livanov (on his 100th anniversary of his scientific,
      scientific-organizational, pedagogical and public activities].

PMID- 17022471
TI  - [Hypothesis of "immunological testing" of partners--systems of "friend and foe"
      recognition in historical prospect].
AB  - The hypothesis of "autoimmune testing" of mating partners assumes formation of
      individual system of perception on the basis of an immunologic principle, i.e. by
      lifetime selection of "direct" or "reverse casts" of own key antigens or signal
      molecules. Such system provides the coordinated change of signaling systems and
      system of their perception at formation of new adaptations that leads to
      automatic formation of reproductive isolation within the limited number of
      generations. Presence of the "friend-foe" recognition systems practically in all
      living organisms assumes formation of potential mating partners "autoimmune
      testing" mechanisms at the earliest evolution stages. In this article we analyze
      possible mechanisms of a "friend and foe" discrimination with MHC-proteins and
      their homologues in historical prospect--from bacteria to the lower Chordates.

PMID- 17022472
TI  - [Equations describing changing of mass and intensity of oxygen consumption during
      post-embryonal animal development].
AB  - Equations fitting changing of mass and mass specific rate of oxygen consumption
      during post-embryonal animal development are deduced from formulae of
      thermodynamics of linear irreversible processes. Requirements of applicability of
      the equations as well as requirements allowing to reduce the growth equation to
      Bertalanffi's equation and changing of mass specific rate of oxygen consumption
      with body mass to allometric dependence are described.

PMID- 17022473
TI  - [Chemical signaling in plant microspore cells].
AB  - Chemical signal transduction from the cell surface to organelles was studied in
      unicellular vegetative (Equisetum arvense) and generative (Hippeastrum hybridum
      pollen) microspores of plants. Neurotransmitters acetylcholine, dopamine, and
      serotonin, their agonists and antagonists, Na+, K+, and Ca2+ channel blockers, as
      well as forskolin and theophylline (agents increasing the intracellular level of
      cyclic adenosine monophosphate) were used as chemical signals. Both types of
      microspores exposed to neurotransmitters, their agonists, forskolin, and
      theophylline demonstrated growth activation, while neurotransmitter antagonists
      and ion channel blockers inhibited this process. No stimulating effects of
      neurotransmitters were observed for cells pretreated with the antagonists and ion
      channel blockers. Pretreatment with ion channel blockers and then by
      anticontractile agents (cytochalasin B or colchicine) either had no effect or
      increased the inhibition of microspore growth. Pathways of chemical signal
      transduction from the cell surface to organelles are discussed.

PMID- 17022474
TI  - [Analysis of expression of regulatory genes Pax6, Prox1, and Pitx2 in
      differentiating eye cells in human fetus].
AB  - Expression of transcription factors PAX6, PROX1, and PITX2 was evaluated in eye
      tissues after 9.5 and 22.0 weeks of human fetus development using polymerase
      chain reaction. Pax6, Prox1 and Pitx2 expression has been revealed in the cornea,
      lens, retina, and eye membranes (total preparation of the pigment epithelium,
      choroid, and sclera) after 9.5 weeks of prenatal development with the maximum
      expression of Pax6 gene in all studied tissues. After 22.0 weeks of development,
      Pax6 expression increased in the retina and lens but decreased in the cornea.
      Insignificant levels of Pax6 transcription have been detected in the eye
      membranes. Prox1 expression was apparent in the cornea, lens, retina, and eye
      membranes after 9.5 weeks. After 22.0 weeks, Prox1 expression increased in the
      lens and retina, decreased in the cornea, and was undetectable in the eye
      membranes. High level of Pitx2 expression has been revealed in all studied eye
      tissues after 9.5 weeks with the lowest transcription level observed in the
      retina. After 22.0 weeks, Pitx2 expression notably decreased in the lens and
      cornea and became undetectable in the retina and eye membranes. The differential
      pattern of Pax6, Prox1 and Pitx2 expression in developing human eye tissues after
      9.5 and 22.0 weeks of development agrees with our histological data.

PMID- 17022475
TI  - [Subcellular localization, purification, and various catalitic properties of
      aspartate aminotransferase from Spirodela polyrhiza].
AB  - Intracellular distribution of aspartate aminotransferase (AAT) in Spirodela
      polyrhiza (Lemnaceae), strain SJ, has been studied by differential
      centrifugation. The bulk of the enzyme (73% of total cellular content) was
      localized in the cytoplasm and 24% activity was localized in chloroplasts.
      Purified cytoplasmic and chloroplastic isozymes differed by their affinity for
      substrates. The reaction balance was shifted towards direct and reverse
      transamination in the cytoplasm and chloroplast, respectively. Competitive
      inhibition of AAT by excessive substrates and enzyme affinity modulation by
      certain intermediates of the tricarboxylic acid cycle (isocitrate, succinate, and
      citrate) were observed. Possible involvement of AAT isozymes in the coordination
      of carbon and nitrogen metabolism through the regulation of 2-oxoglutarate
      synthesis and utilization in different cellular compartments is discussed.

PMID- 17022476
TI  - [Interspecies polymorphism of peroxidase genes, localized on chromosome 5 of
      Arabidopsis thaliana].
AB  - Comparative analysis of nucleotide sequences in five peroxidase genes AtPrx52
      AtPrx56 located in the left arm of chromosome 5 was performed by using six
      Arabidopsis thaliana ecotypes and lines (Columbia, Dijon-M, Blanes-M, Enkheim-M,
      Ler, K-156). Significal differences (up to 20 times) in the levels of nucleotide
      variation between these genes were detected: tandem duplicated genes AtPrx53 and
      AtPrx54 have the highest and the AtPrx56 gene has the lowest level of nucleotide
      diversity. The genes AtPrx53 and AtPrx54 were characterized by allelic
      dimorphism; the nonrandom association between nucleotide polymorphic sites within
      the AtPrx54 was shown. The connection between gaplotype of these genes and the
      mobility of anionic peroxidase izoforms was detected. Since two gaplotypes of
      AtPrx53 were coding proteins, which differed by two significant amino acid
      substitutions, we supposed that differences in mobility of anionic peroxidase
      izoforms caused by the diallelic polymorphism in amino acid sequence of AtPrx53
      protein.

PMID- 17022478
TI  - [Interactions between dopamine, serotonin and other internal reinforcement
      factors].
AB  - The big volume of odd literature data (period 1960-2005) was investigated for
      analysis and estimation of interactions between dopamine (DA), serotonin (5-HT),
      reward factors and basic members of regulatory peptide (RP) families. Database,
      which includes information about physiological effect directions, doses and
      administration types of RP and biological active compounds, organism types, organ
      tissues systems and receptor mechanisms was created. The complex cascade
      interactions between DA, 5-HT, reward factors and RP were investigated and
      systemized. Based on analysis of correlated functiong of DA and 5-HT-systems, the
      opponent-reciprocal interactions were established and their integrative
      characteristics were estimated.

PMID- 17022477
TI  - [Morphophysiological monitoring of winter wheat at spring in connection with
      problem of global climate change].
AB  - Data on morphophysiological monitoring of winter wheat (Triticum aestivum L.)
      cultivar Mironovskaya 808 grown in Hoagland and Arnon solution in a greenhouse
      and transferred to natural conditions in March-April 2004 with the mean daily
      temperature of 0.6 +/- 0.7 degrees C within the exposure period of 42 days are
      presented. Water content, dry weight of plants and their organs, frost hardiness
      of plants, degree of tissue damage by frost, CO2 metabolism (photosynthesis and
      respiration), concentrations of sugars in tissues and proportions between
      different sugar forms, and activities of soluble and insoluble acid and alkaline
      phosphatases were monitored. Monitoring was carried out for three experimental
      variants simulating different microclimatic conditions in spring: after snow
      melting (experiment I), under ice crust (experiment II), and under snow cover
      (experiment III). Plants in experiments III and II demonstrated a higher water
      content in tissues, lower frost hardiness, higher rates of biomass loss, lower
      concentration of sugars and lower di- to monosaccharide ratio in tissues, and
      higher total invertase activity, particularly, cell wall-associated acid
      invertase activity. The dark respiration rates at 0 degrees C did not
      significantly differ between experimental variants. The photosynthetic capacity
      at this measurement temperature was maintained in all experimental variants being
      most pronounced in experiment II with the most intense photoinhibition under
      natural conditions. Comparison of experiments III and II with experiment I is
      used to discuss the negative effect of changes in certain microclimatic variables
      associated with global warming and leading to plant extortion and death from
      frost in spring.

PMID- 17022479
TI  - [Seasonal variation in the content of free reducing sugars in body fluids of
      freshwater mollusk Lymnaea stagnalis].
AB  - Accumulation of certain mono- and disaccharides in body fluids of ectotherms in
      autumn and winter suggests their protective role in adaptation to near-zero
      temperatures. In this context, the effect of seasonal temperature variation on
      the content of free reducing sugars was studied in freshwater snail Lymnaea
      stagnalis. The summer and autumn carbohydrate spectrum essentially featured high
      concentrations of fructose and glucose. After 2.5-month hypobiosis (4 degrees C),
      the concentration of fructose and glucose decreased 35 and 12 times,
      respectively. Maltose and other disaccharides (presumably cellobiose)
      undetectable in summer became detectable in autumn before hypobiosis started. The
      subsequent level of maltose increased to almost reach the sharply decreased
      glucose level and to exceed the fructose level after 2.5-month hypobiosis. The
      involvement of maltose in the mechanisms of L. stagnalis adaptation to near-zero
      temperatures as a membrane protectant is proposed.

PMID- 17022480
TI  - [Effect of prenatal hypoxia during organogenesis on albino rat behavior during
      postnatal period].
AB  - The survival rate, physical development, and spontaneous behavior has been
      evaluated in pups of albino rats exposed to acute hypobaric hypoxia on the 9-10th
      day of gestation corresponding to the onset of organogenesis. Prenatal hypoxia
      increased the mortality among the offspring, delayed their physical development,
      and affected their spontaneous behavior up to the age of 2 months. The females
      exposed to intrauterine hypoxia proved to be more sensitive to hypoxia than
      males.

PMID- 17022481
TI  - [Ecological description of the ground beetle population (Coleoptera, Carabidae)
      in northern taiga meadows of Arkhangel'sk Region].
AB  - Species composition and ecological structure of ground beetle population was
      studied in northern taiga meadows of the Arkhangelsk Region. Meadows in the
      northern forest zone proved to harbor 91 ground beetle species. Carabid complexes
      formed in the intrazonal biocenoses of the northern forest zone can be as rich as
      the topical groups of the family in the southern forest zone by the number of
      species and ecological diversity. Ecological properties of the fauna and ground
      beetle population proved similar in different parts of the forest zone. The
      proportion of stenobiotic meadow species proved to decrease while that of
      ecologically plastic ones increased from south to north. The proportion of the
      genus Harpalus decreased in the ground beetle population while the number of
      Amara species remained unaltered and their abundance increased. The changes in
      the species composition caused no transformation of the ecological structure of
      ground beetle population since they are limited to a single life form or guild.

PMID- 17022482
TI  - [Use of micromycetes Trichoderma for soil bioremediation in tree nurseries].
AB  - Data were obtained on the improvement of soil microbiocenoses in artificial
      ecosystems after the introduction of micromycetes Trichoderma. Application of
      biologically active substances released by some of aboriginal microbial strains
      can solve bioremediation problems in a given region at a low cost.

PMID- 17022483
TI  - [Number and structure of actinomycetes complexes in the rhizosphere winter rye,
      oat and red clover].
AB  - The actinomycetes complexes in the rhizosphere of three agricultural plants by
      using the methods of luminescense microscopy and cup sowing were investigated. It
      was established, that concentration of prokaryotic biomass and biomass of
      actinomycetes mycelium in rhizosphere of plants is higher than in free from the
      radicals to soil. Rhizosphera of the oat (Avena sativa L.) and red clover
      (Trifolium pratense L.) is colonized by Streptomyces, Micromonospora and
      olygospore species. Dominante actinomycetes of winter rye (Secale cereale L.) are
      classified into the genera Micromonospora. It was shown that numbers and biomass
      of actinomycetes mycelium were fond to decreased, diversity of actinomycetes in
      contrast is increased in the series: "winter rye--oat--red clover". In connection
      with ecological safety the capability of increase with prokaryotes naturally
      disease suppressive soil and stability of plants to pathogen is discussed.

PMID- 17022484
TI  - [Effect of tobacco mosaic virus strains on the ultrastructure of parenchymal
      tobacco leaf cells].
AB  - It is shown that considerable amount of virus particles accumulates in the
      parenchymal cells infected with any of strains of tobacco mosaic virus (TMV)
      isolated from affected plants of papper (TMV-p), tomato (TMV-t), eggplant (TMV
      e). Along with normal, abnormal (swolled and "thin") virions were found that
      testifies to their destruction. In reply to infection, activation of the
      lysosomal compartment was observed in the cells that expressed in the formation
      of cytoplasmic vacuoles, dyctiosomes, smooth endoplasmic reticulum elements,
      different vesicles, mitochondria with invaginations, multivesicular bodies. It is
      established that the investigating strains, in dependence on degree of
      stimulation of lysosomal compartment and development of intracellular lytic
      processes causing the destruction of virus particles and cellular structures, may
      be arranged as follows: TMV-p, TMV-e, TMV-t.

PMID- 17022485
TI  - [Fractal structures in living beings and the evolutionary process ].
AB  - Fractal structures of living beings are discussed in the aspect of the
      directionality, i.e., programmed nature, of the evolutionary process. These
      theses are substantiated by analyzing the alternative views of Darwinism and
      Nomogenesis on the nature of biological evolution, in the context of the
      interdisciplinary approach, using the fractal concept, as well as based on the
      nature of the chaotic (fractal) attractors bearing non-random order-generating
      sequences. Apparently, along with the influence of natural selection representing
      the adaptive stage of evolution, the non-random order-generating sequences are
      the governing factor of the directionality and the programmed nature of
      biological evolution, thus representing its progressive form. A number of
      questionable and complicated problems and phenomena of the evolution of organic
      world that are difficult to explain by Darwinism, Nomogenetic theory, or by the
      Synthetic Theory of Evolution are discussed from this viewpoint. These are, in
      particluar, the nature of polymorphic series in plants and animals, M. Eigen's
      hypercycles, and Vavilov's homologous series in hereditary variation.

PMID- 17022486
TI  - [Evolutionary saltations and evolution].
AB  - The term saltation is a composite notion covering different categories of
      supposed saltational evolutionary changes. One can distinguish interspecies,
      macroevolutionary and morphofunctional saltations corresponding to saltational
      arising of a new species, of general Bauplans of new macrotaxons, and of large
      scale morphofunctional alterations (irrelevant to any taxonomic aspects). Current
      data confirm the possibility of interspecies and mophofunctional saltations as
      relatively rare modes of evolutionary changes. Morphofunctional saltations result
      in the arising of macromorphoses that can sometimes stimulate the beginning of
      macroevolutionary typogenesis. Saltationism extremely exaggerates the
      evolutionary role of saltations, considering these to be the main factor of
      speciation and macroevolution. However, saltations are only peculiar and
      relatively rare form of hereditary variability representing elementary
      evolutionary material. Natural selection is the principal evolutionary mechanism
      that produces new adaptations and integrates different systems of the organism in
      the process of typogenesis. The arising of general Bauplans of new macrotax by
      means of macroevolutionary saltations seems to be improbable.

PMID- 17022487
TI  - [Formation of passerine (Passeriformes) vocalization in ontogeny: the current
      state of the problem].
AB  - It the acoustic signal system of birds, songs and calls are distinguished. Up to
      the late 1970s, the attention of researchers was focused primarily on studying
      the process of song formation; the patterns of the call system formation remained
      virtually unstudied. In this field, the prevailing notion was that, since all
      calls are hereditary, their formation in the repertoire of all birds is similar.
      This notion was based on non-passerine birds, for which calls constitute most of
      the vocal communication. Most calls can, indeed, be formed without learning, even
      in nestlings raised in isolation. Yet some calls remain and are transferred in
      populations only through learning. The stages of sound repertoire development
      reflect crucial reorganizations of the acoustic behaviour of nestlings and are
      distinctly recognizable in most of the studied birds. The first three stages
      coincide with the periods of postnatal development of altricial birds
      distinguished by researchers from other fields (based on morphological,
      behavioural, and physiological characters). These are the early nestling, later
      nestling, and post-nestling periods. Two more periods may, however, be
      distinguished in the formation of vocalization: the fourth, confined to the
      period of hormonal reorganization of the organism during the autumn moult, and
      the fifth, coinciding with the beginning of the first reproductive cycle of the
      young bird. The formation of calls in representatives of different systematic
      groups (to families inclusive) can follow three principal paths: independent,
      successive, or explosive. Data on the development of the specific repertoire of
      acoustic signals in ontogeny can serve as a reliable taxonomic criterion,
      assisting in reconstructing and specifying phylogenetic relationships between
      different bird lineages.

PMID- 17022488
TI  - [Population genetic structure of the char species of the Northern Kuril Islands
      and the rank of the Dolly Varden Char in the system of the genus Salvelinus
      (Salmonidae: Teleostei)].
AB  - Analysis of the taxonomic position of most species and forms of the char (genus
      Salvelinus, Salmonidae: Teleostei) was made based on RAPD-PCR. The material was
      represented by samples from 29 populations from the Kuril Islands, coast of the
      Sea of Okhotsk, Kamchatka, Chukotka, Taymyr, Transbaikalia, the Kola Peninsula,
      Svalbard, Finland, and North America. It was shown that the genus Salvelinus
      splits into three well-justified clusters: (1) all the forms assigned to the
      Salvelinus alpinus--S. malma complex; (2) two samples of the White-Spotted Char
      from the Southern Kuril Islands and from Kamchatka; (3) two North American
      species, S. fontinalis and S. namaycush (samples of the North American species S.
      confluentis were absent from the collection). Analysis of the absolute values of
      genetic disctances of the S. alpinus--S. malma forms relative to S. leucomaenis,
      S. fontinalis, and S. namaycush revealed distances approaching the species rank
      between the following isolates: Frolikh Char, Mountain Char, Black Lake Char,
      Goggle-Eyed Char, and Neyva Char. Samples of Dolly Varden currently considered as
      "S. malma", do not constitute a separate cluster, falling within the group of the
      Arctic char S. alpinus. This conclusion is supported by the analysis of the
      results of three series of experiments by R. Phillips on ITS1 ribosome genes
      (Pleute et al., 1992; Phillips et al., 1995; Phillips et al., 1999). This
      indicates the infraspecific rank of malma within S. alpinus. Isolated populations
      of "Salvethymus svetovidovi" from the lake Elgygytgyn (Chukotka Peninsula) and of
      the char from the lake Chyornoye (Onekotan Island), recently described as S.
      gritzenkoi (Vasil'eva, Stygar, 2000), fell withing the S. alpinus--S. malma
      complex, the Onekotan char grouped together with another isolate from the same
      island. Comparison of genetic distances between the samples showed that the
      differences between the two isolated of Onekotan and migratory forms of the Kuril
      Islands are approximately equal, yet the homogeneity of the Chyornoye sample is
      higher than that of the other samples. The revealed 330-nucleotide diagnostic
      sequence of the Onekotan lake isolate showed identity of part of the fragment
      with a section of expressed DNA from the library of EST clones derived from the
      gills of Salmo salar, this possibly indicates the adaptive character of the
      evolution.

PMID- 17022489
TI  - [Quantitative estimation of the dynamics of adventive flora (by the example of
      the Tula region)].
AB  - The rate of enrichment of the Tula region flora with adventive species was
      quantitatively estimated taking into account the changes of their degree of
      naturalization during the last 200 years. Numerical score of degree of the
      naturalization for each species was used to compile the initial database: "0",
      species absent from the territory; "1", ephemerophyte; "2", colonophyte; "3",
      epecophyte; "4", argiophyte; "?", lack of data. Non-interpolated integral index
      of the dynamics of adventive flora NI(t) was calculated from this database. This
      index displays the sum of the degrees of naturalization of all the adventive
      species in the flora in some particular year. The interpolation of the initial
      database, aimed at minimizing the influence of random factors (e.g., gaps in
      observations or different activity of the researchers in different years), was
      performed by substituting the "?" symbol by a series of intermediate values based
      on studies of the data for adjacent territories. Interpolated integral indices
      I(t) were calculated from the interpolated database. These indices were then
      leveled out with Morlet wavelets, in order to distinguish random spikes (lasting
      less than 50 years) from the analyzed signal, and thus approximate the index
      dynamics to the objective trend that represents the dynamics of the flora and not
      the rate of activity of the researchers. The dynamics of the adventive flora of
      the Tula region revealed with this method shows the following facts: 1) average
      rate of the enrichment of the adventive flora with strange species has been
      constant for these 200 years and amounted to 15 species per decade; 2) average
      rate of naturalization was relatively low and constant, amounting to 5 species
      per decade; 3) fluctuations of the composition and naturalization degree of the
      Tula region adventive flora species were not shown to be dependant directly on
      the changes in the territory's economic development during the last two
      centuries; 4) no periodicity was recorded in the advent of new species, and the
      fluctuations of the number of adventive species can be attributed to the
      fluctuations of research intensity.

PMID- 17022490
TI  - [The continuity and discontinuity of the living cover: problem of the scale].
AB  - The reply to B.M. Mirkin's critical remarks (2005) concerning my paper
      "Continuity and discontinuity of the geomerida: the bionomic and biotic aspects"
      (Kafanov, 2005a) is given. The relationship between continuity and discontinuity
      of the living cover depends on the scale of study. The continuum mainly belongs
      to regularities of topological order. At regional, subglobal and global scale,
      the continuum of biochores is rather rare. The objective evidences of relative
      discontinuity of the living cover are determined by significant alterations of
      taxonomic richness at regional, subglobal and global scale.

PMID- 17022491
TI  - [IGT].

PMID- 17022492
TI  - [IFG].

PMID- 17022493
TI  - [Postprandial hyperglycemia].

PMID- 17022494
TI  - [Type 1 diabetes mellitus].

PMID- 17022495
TI  - [Slowly progressive insulin-dependent (type 1) diabetes mellitus].

PMID- 17022496
TI  - [Fulminant type 1 diabetes].

PMID- 17022497
TI  - [Type 2 diabetes mellitus].

PMID- 17022498
TI  - [Gestational diabetes mellitus].

PMID- 17022499
TI  - [MODY].

PMID- 17022500
TI  - [Mitochondrial diabetes mellitus].

PMID- 17022501
TI  - [Type A or type B syndrome of insulin resistance].

PMID- 17022502
TI  - [Diabetes mellitus due to exocrine pancreatic diseases].

PMID- 17022503
TI  - [Diabetes secondary to endocrinopathies].

PMID- 17022504
TI  - [Diabetes mellitus in chronic liver disease].

PMID- 17022505
TI  - [Diabetes mellitus induced by drugs and chemical agents].

PMID- 17022506
TI  - [Diabetes associated with infection].

PMID- 17022507
TI  - [Soft drink ketosis].

PMID- 17022508
TI  - [Leprechaunism (Donohue syndrome)].

PMID- 17022509
TI  - [Aceruloplasminemia (hereditary ceruloplasmin deficiency) and diabetes mellitus].

PMID- 17022510
TI  - [Myotonic dystrophy].

PMID- 17022511
TI  - [Lipoatrophic diabetes].

PMID- 17022512
TI  - [Ataxia-telangiectasia].

PMID- 17022513
TI  - [Down syndrome].

PMID- 17022514
TI  - [Herrmann syndrome].

PMID- 17022515
TI  - [Rabson-Mendenhall syndrome].

PMID- 17022516
TI  - [Stiff-Man syndrome].

PMID- 17022517
TI  - [Werner's syndrome].

PMID- 17022518
TI  - [Wolfram syndrome].

PMID- 17022519
TI  - [Diabetic ketoacidosis].

PMID- 17022520
TI  - [Hyperglycemic hyperosmolar non-ketotic coma].

PMID- 17022521
TI  - [Diabetic lactic acidosis].

PMID- 17022522
TI  - [Diabetic neuropathy].

PMID- 17022523
TI  - [Diabetic retinopathy-state of arts of diagnosis and treatment].

PMID- 17022524
TI  - [Diabetic nephropathy].

PMID- 17022525
TI  - [Diabetic skin disorders].

PMID- 17022526
TI  - [Neonatal hypoglycemia].

PMID- 17022527
TI  - [Ketotic hypoglycemia in childhood].

PMID- 17022528
TI  - [Drug-induced hypoglycemia].

PMID- 17022529
TI  - [Insulinoma].

PMID- 17022531
TI  - [Insulin autoimmune syndrome].

PMID- 17022530
TI  - [Non-islet cell tumor hypoglycemia (NICTH)].

PMID- 17022532
TI  - [Ectopic insulin secretion].

PMID- 17022533
TI  - [Hypoglycemia due to endocrine deficiencies].

PMID- 17022535
TI  - [Hereditary fructose intolerance].

PMID- 17022534
TI  - [Galactosemia].

PMID- 17022536
TI  - [Postprandial hypoglycemia].

PMID- 17022537
TI  - [Idiopathic reactive hypoglycemia].

PMID- 17022538
TI  - [Congenital leptin deficiency].

PMID- 17022539
TI  - [Clinical and biological consequences of leptin receptor mutation].

PMID- 17022540
TI  - [Prohormone convertase 1 (PC1) gene mutation].

PMID- 17022541
TI  - [POMC gene mutations in human].

PMID- 17022542
TI  - [Melanocortin-4 receptor gene mutations associated with obesity].

PMID- 17022543
TI  - [Mutations and polymorphisms in adiponectin gene].

PMID- 17022544
TI  - [Ectopic neurotensin-producing tumors].

PMID- 17022545
TI  - [Ectopic ACTH syndrome].

PMID- 17022546
TI  - [Ectopic GHRH (growth hormone-releasing hormone) producing tumor].

PMID- 17022547
TI  - [Ectopic erythropoietin-producing tumor].

PMID- 17022548
TI  - [Ectopic calcitonin-producing tumor].

PMID- 17022549
TI  - [Ectopic thyroid hormone producing tumor].

PMID- 17022550
TI  - [Ectopic ADH-producing tumor].

PMID- 17022551
TI  - [Human chorionic gonadotropin in non-trophoblastic cancer].

PMID- 17022553
TI  - [Ectopic prolactin-producing tumor].

PMID- 17022552
TI  - [Ectopic growth hormone-producing tumor].

PMID- 17022554
TI  - [Ectopic renin-producing tumor].

PMID- 17022555
TI  - [PTH-related protein producing tumor].

PMID- 17022556
TI  - [Serotonin producing tumors (carcinoid tumors and carcinoid syndrome)].

PMID- 17022557
TI  - [Paraneoplastic endocrine syndrome].

PMID- 17022558
TI  - [Multiple endocrine neoplasia type I].

PMID- 17022559
TI  - [Multiple endocrine neoplasia type IIa (MEN2A)].

PMID- 17022560
TI  - [Multiple endocrine neoplasia type IIb].

PMID- 17022561
TI  - [Von Recklinghausen's disease].

PMID- 17022562
TI  - [Von Hippel-Lindau disease].

PMID- 17022563
TI  - [PPoma].

PMID- 17022564
TI  - [Vasoactive intestinal peptide-producing tumor (ViPoma)].

PMID- 17022565
TI  - [Gastrinoma].

PMID- 17022566
TI  - [Glucagonoma].

PMID- 17022567
TI  - [Somatostatinoma].

PMID- 17022569
TI  - [Breast cancer].

PMID- 17022568
TI  - [Paraneuroma (APUDoma)].

PMID- 17022570
TI  - [Endometrial carcinoma].

PMID- 17022571
TI  - [Prostate cancer].

PMID- 17022572
TI  - [Aarskog-Scott syndrome].

PMID- 17022573
TI  - [Biemond syndrome].

PMID- 17022574
TI  - [Bloom syndrome].

PMID- 17022575
TI  - [Borjeson-Forssman-Lehmann syndrome].

PMID- 17022576
TI  - [Cockayne syndrome].

PMID- 17022577
TI  - [Crouzon syndrome].

PMID- 17022578
TI  - [Fanconi's pancytopenia syndrome].

PMID- 17022579
TI  - [Goltz syndrome].

PMID- 17022580
TI  - [Leri-Weill syndrome].

PMID- 17022581
TI  - [Multiple pterygium syndrome].

PMID- 17022582
TI  - [Russell-Silver syndrome].

PMID- 17022583
TI  - [Williams syndrome].

PMID- 17022584
TI  - [Familial short stature].

PMID- 17022585
TI  - [Fetal alcohol syndrome (FAS)].

PMID- 17022586
TI  - [CHARGE syndrome].

PMID- 17022587
TI  - [Denys-Drash syndrome].

PMID- 17022588
TI  - [LEOPARD syndrome].

PMID- 17022589
TI  - [Lowe syndrome].

PMID- 17022590
TI  - [Martsolf syndrome].

PMID- 17022591
TI  - [Oliver-McFarlane syndrome].

PMID- 17022592
TI  - [Rothmund-Thomson syndrome].

PMID- 17022593
TI  - [Rud syndrome].

PMID- 17022594
TI  - [Smith-Lemli-Opitz syndrome].

PMID- 17022596
TI  - [Steroid sulphatase deficiency].

PMID- 17022595
TI  - [Sohval-Soffer syndrome].

PMID- 17022597
TI  - [Endocrine diseases with hypertension].

PMID- 17022598
TI  - [Estrogen-induced hypertension].

PMID- 17022599
TI  - [Pregnancy induced hypertension].

PMID- 17022601
TI  - [Juxtaglomerular cell tumor].

PMID- 17022600
TI  - [Erythropoietin-induced hypertension].

PMID- 17022602
TI  - [Low renin hypertension].

PMID- 17022603
TI  - [Endocrine disorders associated with hypokalemia and hyperkalemia].

PMID- 17022604
TI  - [Endocrine disorders producing hyponatremia or hypernatremia].

PMID- 17022605
TI  - [Endocrine diseases presenting with hypo- or hypercalcemia].

PMID- 17022606
TI  - [Endocrine diseases accompanied by hypophosphatemia or hyperphosphatemia].

PMID- 17022607
TI  - [Endocrine diseases with hypomagnesemia].

PMID- 17022608
TI  - [PADAM].

PMID- 17022609
TI  - [Autoimmune polyglandular syndrome (type 1, 2, 3, 4)].

PMID- 17022610
TI  - [Renal failure and endocrine insufficiency].

PMID- 17022611
TI  - [Radiation-induced endocrinopathy].

PMID- 17022612
TI  - [Lisosomal disease with endocrine abnormality].

PMID- 17022613
TI  - [Familial tall stature/constitutional tall stature].

PMID- 17022614
TI  - [Beckwith-Wiedemann syndrome].

PMID- 17022615
TI  - [Hall syndrome (Pallister-Hall syndrome)].

PMID- 17022616
TI  - [Hutchinson-Gilford syndrome].

PMID- 17022617
TI  - [Kearns-Sayre syndrome].

PMID- 17022618
TI  - [POEMS syndrome (Crow-Fukase syndrome)].

PMID- 17022619
TI  - [WAGR syndrome].

PMID- 17022620
TI  - [Primary hemochromatosis as a disease provoked by hepcidin deficiency?].

PMID- 17022622
TI  - The implausibility of systemic genotoxic effects measured by the comet assay in
      rats exposed to formaldehyde.
AB  - A recent publication reported genotoxic effects in the alkaline comet assay in
      lymphocytes and liver cells of rats exposed to formaldehyde (FA) by inhalation
      (Im,H.; et al. J. Proteome Res. 2006, 5, 1354-1366). Rats were exposed to 5 and
      10 ppm FA for 2 weeks in inhalation chambers. A similar dose-related increase in
      DNA migration was measured in both cell types. These results are inconsistent
      with published data concerning FA toxicity: (i) Systemic genotoxic effects are
      reported, whereas previous animal experiments indicated only local effects. (ii)
      Similar effects were observed in liver cells and lymphocytes despite
      administration by inhalation. (iii) Increased DNA migration was measured, whereas
      FA-induced DNA-protein cross-links (DPX) should reduce DNA migration. These three
      aspects are critically discussed, and the plausibility of the results published
      by Im and colleagues is questioned.

PMID- 17022623
TI  - Evaluation of toxicological monitoring markers using proteomic analysis.
AB  - In our study, we chose three different concentrations of FA (0, 5, and 10 ppm),
      and cytotoxic (lipid peroxidation and protein oxidation) and genotoxic assays
      (DNA damage) were carried out on plasma, blood, and liver cells of rats subjected
      to FA-inhalation treatment. The profiles of plasma protein changes determined
      using 2-DE analysis were also evaluated to identify potential toxicological
      monitoring markers in FA-exposed rats. Concern was raised that our genotoxic
      analyses did not follow previously published research data and that the results
      of our rat plasma proteomic studies were difficult to interpret because we did
      not directly determine the plasma concentration of FA. However, we had already
      determined the concentration of FA using HPLC in an exposure chamber to monitor
      FA inhalation concentrations. We suggest that our experimental design was
      suitable to determine the FA effects on rat using an inhalation chamber system.
      For the similarity of genotoxic effects in lymphocytes and liver cells, we chose
      to present our data on the general cytological toxic effects on lipid
      peroxidation and protein oxidation which revealed a similarity between plasma and
      liver cells of FA-exposed rats. We have shown strong correlations between
      genotoxicity and lipid peroxidation, and lipid peroxidation is known to mediate
      DNA damage in many in vitro, and in vivo studies. We are well aware of the
      'implausibility' of leukemia induction by FA, but for precisely this reason, we
      feel the need for further study to prove the systemic genotoxic effects of FA.

PMID- 17022621
TI  - Nanotools for megaproblems: probing protein misfolding diseases using
      nanomedicine modus operandi.
AB  - Misfolding and self-assembly of proteins in nanoaggregates of different sizes and
      morphologies (nanoensembles, primary nanofilaments, nanorings, filaments,
      protofibrils, fibrils, etc.) is a common theme unifying a number of human
      pathologies termed protein misfolding diseases. Recent studies highlight
      increasing recognition of the public health importance of protein misfolding
      diseases, including various neurodegenerative disorders and amyloidoses. It is
      understood now that the first essential elements in the vast majority of
      neurodegenerative processes are misfolded and aggregated proteins. Altogether,
      the accumulation of abnormal protein nanoensembles exerts toxicity by disrupting
      intracellular transport, overwhelming protein degradation pathways, and/or
      disturbing vital cell functions. In addition, the formation of inclusion bodies
      is known to represent a major problem in the production of recombinant
      therapeutic proteins. Formulation of these therapeutic proteins into delivery
      systems and their in vivo delivery are often complicated by protein association.
      Thus, protein folding abnormalities and subsequent events underlie a multitude of
      human pathologies and difficulties with protein therapeutic applications. The
      field of medicine therefore can be greatly advanced by establishing a fundamental
      understanding of key factors leading to misfolding and self-assembly responsible
      for various protein folding pathologies. This article overviews protein
      misfolding diseases and outlines some novel and advanced nanotechnologies,
      including nanoimaging techniques, nanotoolboxes and nanocontainers, complemented
      by appropriate ensemble techniques, all focused on the ultimate goal to establish
      etiology and to diagnose, prevent, and cure these devastating disorders.

PMID- 17022624
TI  - Sub-speciating Campylobacter jejuni by proteomic analysis of its protein
      biomarkers and their post-translational modifications.
AB  - We have identified several protein biomarkers of three Campylobacter jejuni
      strains (RM1221, RM1859, and RM3782) by proteomic techniques. The protein
      biomarkers identified are prominently observed in the time-of-flight mass spectra
      (TOF MS) of bacterial cell lysate supernatants ionized by matrix-assisted laser
      desorption/ionization (MALDI). The protein biomarkers identified were: DNA
      binding protein HU, translation initiation factor IF-1, cytochrome c553, a
      transthyretin-like periplasmic protein, chaperonin GroES, thioredoxin Trx, and
      ribosomal proteins: L7/L12 (50S), L24 (50S), S16 (30S), L29 (50S), and S15 (30S),
      and conserved proteins similar to strain NCTC 11168 proteins Cj1164 and Cj1225.
      The protein biomarkers identified appear to represent high copy, intact proteins.
      The significant findings are as follows: (1) Biomarker mass shifts between these
      strains were due to amino acid substitutions of the primary polypeptide sequence
      and not due to changes in post-translational modifications (PTMs). (2) If
      present, a PTM of a protein biomarker appeared consistently for all three
      strains, which supported that the biomarker mass shifts observed between strains
      were not due to PTM variability. (3) The PTMs observed included N-terminal
      methionine (N-Met) cleavage as well as a number of other PTMs. (4) It was
      discovered that protein biomarkers of C. jejuni (as well as other thermophilic
      Campylobacters) appear to violate the N-Met cleavage rule of bacterial proteins,
      which predicts N-Met cleavage if the penultimate residue is threonine. Two
      protein biomarkers (HU and 30S ribosomal protein S16) that have a penultimate
      threonine residue do not show N-Met cleavage. In all other cases, the rule
      correctly predicted N-Met cleavage among the biomarkers analyzed. This exception
      to the N-Met cleavage rule has implications for the development of bioinformatics
      algorithms for protein/pathogen identification. (5) There were fewer biomarker
      mass shifts between strains RM1221 and RM1859 compared to strain RM3782. As the
      mass shifts were due to the frequency of amino acid substitutions (and thus
      underlying genetic variations), this suggested that strains RM1221 and RM1859
      were phylogenetically closer to one another than to strain RM3782 (in addition, a
      protein biomarker prominent in the spectra of RM1221 and RM1859 was absent from
      the RM3782 spectrum due to a nonsense mutation in the gene of the biomarker).
      These observations were confirmed by a nitrate reduction test, which showed that
      RM1221 and RM1859 were C. jejuni subsp. jejuni whereas RM3782 was C. jejuni
      subsp. doylei. This result suggests that detection/identification of protein
      biomarkers by pattern recognition and/or bioinformatics algorithms may easily
      subspeciate bacterial microorganisms. (6) Finally, the number and variation of
      PTMs detected in this relatively small number of protein biomarkers suggest that
      bioinformatics algorithms for pathogen identification may need to incorporate
      many more possible PTMs than suggested previously in the literature.

PMID- 17022625
TI  - Evaluation of D10-Leu metabolic labeling coupled with MALDI-MS analysis in
      studying the response of the yeast proteome to H2O2 challenge.
AB  - An efficient D10-Leu metabolic-labeling method combined with isotope-ratio
      quantitation by MALDI-TOF MS was used to probe the response of the yeast proteome
      to H2O2. Control cultures correct for effects not associated with H2O2 challenge.
      A stress-response index to H2O2 (SRIH2O2) is defined, and values are reported for
      seven proteins at 45-225 min following exposure to 0.4 mM H2O2. The time course
      of protein accumulation in unstressed cells following the H10- to D10-SCD switch
      suggests that proteome responses at <45 min could be monitored by addition of
      excess D10-Leu to H10-cultures.

PMID- 17022626
TI  - Evaluation of the application of sodium deoxycholate to proteomic analysis of rat
      hippocampal plasma membrane.
AB  - Detergents have been widely used for the solubilization of membrane proteins and
      the improvement of their digestion. In this paper, we have evaluated the
      application of sodium deoxycholate (SDC) to the solubilization and digestion of
      rat hippocampal plasma membrane (PM) proteins. For in-solution digestion, rat
      hippocampal PM fraction from sucrose-density gradient centrifugation was
      solubilized by boiling in 1.0% SDC, and directly digested without dilution.
      During the in-gel digestion of the hippocampal PM proteins separated by SDS-PAGE,
      0.1% SDC was added. Before analysis of peptide mixture by liquid chromatography
      and electrospray mass spectrometry, SDC in the tryptic digests was removed by
      centrifugation following acidification. Use of 1.0% SDC in solubilization and in
      solution digestion of rat PM proteins had led to 77 PM or membrane-associated
      proteins identified, a more than 2-fold increase over that by use of SDS. The
      addition of 0.1% SDC to the in-gel digestion of SDS-PAGE-resolved membrane
      proteins remarkably enhanced the coverage of tryptic peptides and the number of
      hydrophobic membrane proteins identified. Being a cheaper and more tractable acid
      insoluble detergent, SDC could be used at higher concentration in the
      solubilization and tryptic digestion of proteins including PM proteins with the
      purpose of enhancing the protein solubility and at the same time making no
      interference with trypsin activity and subsequent analyses.

PMID- 17022627
TI  - Age-related changes in human crystallins determined from comparative analysis of
      post-translational modifications in young and aged lens: does deamidation
      contribute to crystallin insolubility?
AB  - We have employed recently developed blind modification search techniques to
      generate the most comprehensive map of post-translational modifications (PTMs) in
      human lens constructed to date. Three aged lenses, two of which had moderate
      cataract, and one young control lens were analyzed using multidimensional liquid
      chromatography mass spectrometry. In total, 491 modification sites in lens
      proteins were identified. There were 155 in vivo PTM sites in crystallins: 77
      previously reported sites and 78 newly detected PTM sites. Several of these sites
      had modifications previously undetected by mass spectrometry in lens including
      carboxymethyl lysine (+58 Da), carboxyethyl lysine (+72 Da), and an arginine
      modification of +55 Da with yet unknown chemical structure. These new
      modifications were observed in all three aged lenses but were not found in the
      young lens. Several new sites of cysteine methylation were identified indicating
      this modification is more extensive in lens than previously thought. The results
      were used to estimate the extent of modification at specific sites by spectral
      counting. We tested the long-standing hypothesis that PTMs contribute to age
      related loss of crystallin solubility by comparing spectral counts between the
      water-soluble and water-insoluble fractions of the aged lenses and found that the
      extent of deamidation was significantly increased in the water-insoluble
      fractions. On the basis of spectral counting, the most abundant PTMs in aged
      lenses were deamidations and methylated cysteines with other PTMs present at
      lower levels.

PMID- 17022628
TI  - Effect of 2MEGA labeling on membrane proteome analysis using LC-ESI QTOF MS.
AB  - One of the challenges associated with large-scale proteome analysis using tandem
      mass spectrometry (MS/MS) and automated database searching is to reduce the
      number of false positive identifications without sacrificing the number of true
      positives found. In this work, a systematic investigation of the effect of 2MEGA
      labeling (N-terminal dimethylation after lysine guanidination) on the proteome
      analysis of a membrane fraction of an Escherichia coli cell extract by 2
      dimensional liquid chromatography MS/MS is presented. By a large-scale comparison
      of MS/MS spectra of native peptides with those from the 2MEGA-labeled peptides,
      the labeled peptides were found to undergo facile fragmentation with enhanced a1
      or a1-related (a(1)-17 and a(1)-45) ions derived from all N-terminal amino acids
      in the MS/MS spectra; these ions are usually difficult to detect in the MS/MS
      spectra of nonderivatized peptides. The 2MEGA labeling alleviated the biased
      detection of arginine-terminated peptides that is often observed in MALDI and ESI
      MS experiments. 2MEGA labeling was found not only to increase the number of
      peptides and proteins identified but also to generate enhanced a1 or a1-related
      ions as a constraint to reduce the number of false positive identifications. In
      total, 640 proteins were identified from the E. coli membrane fraction, with each
      protein identified based on peptide mass and sequence match of one or more
      peptides using MASCOT database search algorithm from the MS/MS spectra generated
      by a quadrupole time-of-flight mass spectrometer. Among them, the subcellular
      locations of 336 proteins are presently known, including 258 membrane and
      membrane-associated proteins (76.8%). Among the classified proteins, there was a
      dramatic increase in the total number of integral membrane proteins identified in
      the 2MEGA-labeled sample (153 proteins) versus the unlabeled sample (77
      proteins).

PMID- 17022629
TI  - A new approach for the detection and identification of protein impurities using
      combinatorial solid phase ligand libraries.
AB  - We propose a novel method for detection of protein impurities present in plasma
      derived and recombinant purified injectable biopharmaceuticals by enhancing the
      concentration of protein impurities, in essence "amplifying" their presence to
      detectable levels. The method is based on the capture of proteins using a
      combinatorial solid-phase hexapeptides ligand library previously described for
      the reduction of protein concentration difference in biological fluids. Three
      proteins have been investigated: Staphylococcus aureus Protein A, expressed in
      Escherichia coli and supplied as 99% pure, recombinant human albumin, expressed
      in Pichia pastoris and certified as 95% pure, and therapeutic albumin supplied as
      96-98% pure injectable solution. In all cases, after treatment with the ligand
      libraries, a number of additional polypeptide chains, not visible in the control,
      could be detected and obtained in sufficient amounts for MS analysis. In the
      cases of the two recombinant proteins, it could be demonstrated that a number of
      these polypeptide chains were host cell proteins still present in the purified
      product. In addition, a substantial number of these spots were found to be
      cleavage products of the original recombinant DNA species. Such cleavage products
      were particularly abundant in the recombinant human albumin preparation. From
      pure injectable serum albumin, a number of human plasma protein impurities were
      also identified by LC-MS/MS analysis. Treatment with ligand libraries of purified
      proteins is thus seen as a very powerful method of capture and concentration of
      host proteins and cleaved products for further analysis to control better the
      quality of industrial biotechnology products.

PMID- 17022630
TI  - Differential expression of defense/stress-related marker proteins in leaves of a
      unique rice blast lesion mimic mutant (blm).
AB  - We analyzed a unique rice (Oryza sativa L.) blast lesion mimic (blm) mutant for
      differentially expressed proteins in leaves of one- and two-week-old seedlings
      manifesting the lesion mimic phenotype. Gel-based one- and two-dimensional
      electrophoresis (1- and 2-DGE) was performed using leaves (blm and wild-type, WT)
      before (stage 1, S1) and after (stage 2, S2) lesion formation. 1-DGE
      immunoblotting revealed potent increase in the expression of a key pathogenesis
      related (PR) marker biosynthetic enzyme, naringenin 7-O-methyltransferase,
      involved in rice phytoalexin sakuranetin biosynthesis, and three oxidative-stress
      related marker proteins, catalase, ascorbate peroxidase (APX), and superoxide
      dismutase (SOD) in leaves of the blm mutant. 2-D gel immunoblotting analysis with
      anti-APX and anti-SOD antibodies revealed newly appearing cross-reacting protein
      spots in blm. 2-DGE analysis detected 50 Coomassie brilliant blue-stained protein
      spots differentially expressed in blm. A total of 23 and 44 protein spots was
      excised for analysis by N-terminal amino acid sequencing and nano-electrospray
      ionization liquid chromatography mass spectrometry, respectively; 26 nonredundant
      proteins were identified. The pathogenesis-related class 5 and 10 proteins,
      including a new OsPR10d protein, were significantly induced in blm. The OsPR5
      protein spot was stained with Pro-Q Diamond phosphoprotein gel stain suggesting
      OsPR5 to be a putative phosphoprotein. Surprisingly, protein spot 20, a leaf
      OsPR10b, showed identity to a rice root-specific PR-10 (RSOsPR10). To resolve
      this discrepancy, we checked its expression in leaves of blm and WT (S1 and S2),
      respectively, using gene-specific primers and reverse transcriptase-polymerase
      chain reaction; RSOsPR10 mRNA was found to express in the leaves.

PMID- 17022631
TI  - Secreted proteome profiling in human RPE cell cultures derived from donors with
      age related macular degeneration and age matched healthy donors.
AB  - Age-related macular degeneration (AMD) is characterized by progressive loss of
      central vision, which is attributed to abnormal accumulation of macular deposits
      called "drusen" at the interface between the basal surface of the retinal pigment
      epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits
      are accompanied by the growth of new blood vessels that breach the RPE layer and
      invade photoreceptors. In this study, we hypothesized that RPE secreted proteins
      are responsible for drusen formation and choroidal neovascularization. We used
      stable isotope labeling by amino acids in cell culture (SILAC) in combination
      with LC-MS/MS analysis and ZoomQuant quantification to assess differential
      protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD
      donors (diagnosed by histological examinations of the macula and genotyped for
      the Y402H-complement factor H variant) and age-matched healthy control donors. In
      general, RPE cells were found to secrete a variety of extracellular matrix
      proteins, complement factors, and protease inhibitors that have been reported to
      be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE
      cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein,
      fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived
      factor than RPE cells from age-matched healthy donors. Conversely, secreted
      protein acidic and rich in cysteine (SPARC) was found to be down regulated by 2
      fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis
      grouped these differentially secreted proteins into two groups; those involved in
      tissue development and angiogenesis and those involved in complement regulation
      and protein aggregation such as clusterin. Overall, these data strongly suggest
      that RPE cells are involved in the biogenesis of drusen and the pathology of AMD.

PMID- 17022632
TI  - Statistical analysis of the experimental variation in the proteomic
      characterization of human plasma by two-dimensional difference gel
      electrophoresis.
AB  - The complexity of human plasma presents a number of challenges to the efficient
      and reproducible proteomic analysis of differential expression in response to
      disease. Before individual variation and disease-specific protein biomarkers can
      be identified from human plasma, the experimental variability inherent in the
      protein separation and detection techniques must be quantified. We report on the
      variation found in two-dimensional difference gel electrophoresis (2-D DIGE)
      analysis of human plasma. Eight aliquots of a human plasma sample were subjected
      to top-6 highest abundant protein depletion and were subsequently analyzed in
      triplicate for a total of 24 DIGE samples on 12 gels. Spot-wise standard
      deviation estimates indicated that fold changes greater than 2 can be detected
      with a manageable number of replicates in simple ANOVA experiments with human
      plasma. Mixed-effects statistical modeling quantified the effect of the dyes, and
      segregated the spot-wise variance into components of sample preparation, gel-to
      gel differences, and random error. The gel-to-gel component was found to be the
      largest source of variation, followed by the sample preparation step. An improved
      protocol for the depletion of the top-6 high-abundance proteins is suggested,
      which, along with the use of statistical modeling and future improvements in gel
      quality and image processing, can further reduce the variation and increase the
      efficiency of 2-D DIGE proteomic analysis of human plasma.

PMID- 17022633
TI  - Proteome analysis of responses to ascochlorin in a human osteosarcoma cell line
      by 2-D gel electrophoresis and MALDI-TOF MS.
AB  - Ascochlorin is a prenyl-phenol compound that was isolated from the fungus
      Ascochyta viciae. Ascochlorin reduces serum cholesterol and triglyceride levels,
      suppresses hypertension and tumor development, and ameliorates type I and II
      diabetes. Here, to better understand the mechanisms by which ascochlorin
      regulates physiological or pathological events and induces responses in the
      pharmacological treatment of cancer, we performed differential analysis of the
      proteome of the human osteosarcoma cells U2OS in response to ascochlorin. In
      addition, we established the first two-dimensional map of the U2OS proteome. The
      U2OS cell proteomes with and without treatment with ascochlorin were compared
      using two-dimensional electrophoresis, matrix-assisted laser
      desorption/ionization mass spectrometry and bioinformatics. The largest
      differences in expression were observed for the epidermal growth factor receptor
      (4-fold decrease), ribulose-5-phosphate-epimerase (13-fold decrease), ATP
      dependent RNA helicase (8-fold decrease), and kelch-like ECH-associated protein 1
      (6-fold decrease). The abundance of heterogeneous nuclear ribonucleoprotein L and
      minichromosome maintenance protein 7 increased 12- and 8.2-fold, respectively. In
      addition, Erk 2 was increased 3-fold in U2OS cells treated with ascochlorin. The
      expression of some selected proteins was confirmed by western blotting,
      zymography and RT-PCR analysis.

PMID- 17022634
TI  - Quantification of membrane and membrane-bound proteins in normal and malignant
      breast cancer cells isolated from the same patient with primary breast carcinoma.
AB  - More than 50% of all major drug targets are membrane proteins, and their role in
      cell-cell interaction and signal transduction is a vital concern. By culturing
      normal and malignant breast cancer cells with light or heavy isotopes of amino
      acids (SILAC), followed by cell fractionation, 1D gel separation of crude
      membrane proteins, and analysis of the digests using nanoelectrospray LC-MS/MS,
      we have quantified 1600 gene products that group into 997 protein families with
      approximately 830 membrane or membrane-associated proteins; 100 unknown, unnamed,
      or hypothetical proteins; and 65 protein families classified as ribosomal, heat
      shock, or histone proteins. A number of proteins show increased expression levels
      in malignant breast cancer cells, such as autoantigen p542, osteoblast-specific
      factor 2 (OSF-2), 4F2 heavy chain antigen, 34 kDa nucleolar scleroderma antigen,
      and apoptosis inhibitor 5. The expression of other proteins, such as membrane
      alanine aminopeptidase (CD13), epididymal protein, macroglobulin alpha2,
      PZP_HUMAN, and transglutaminase C, decreased in malignant breast cancer cells,
      whereas the majority of proteins remained unchanged when compared to the
      corresponding nonmalignant samples. Downregulation of CD13 and upregulation of
      OSF-2 were confirmed by immunohistochemistry using human tissue arrays with
      breast carcinomas. Furthermore, at least half the gene products displaying an
      expression change of 5-fold or higher have been described previously in the
      literature as having an association with cancerous malignancy. These results
      indicate that SILAC is a powerful technique that can be extended to the discovery
      of membrane-bound antigens that may be used to phenotype diseased cells.

PMID- 17022635
TI  - Statistically integrated metabonomic-proteomic studies on a human prostate cancer
      xenograft model in mice.
AB  - A novel statistically integrated proteometabonomic method has been developed and
      applied to a human tumor xenograft mouse model of prostate cancer. Parallel 2D
      DIGE proteomic and 1H NMR metabolic profile data were collected on blood plasma
      from mice implanted with a prostate cancer (PC-3) xenograft and from matched
      control animals. To interpret the xenograft-induced differences in plasma
      profiles, multivariate statistical algorithms including orthogonal projection to
      latent structure (OPLS) were applied to generate models characterizing the
      disease profile. Two approaches to integrating metabonomic data matrices are
      presented based on OPLS algorithms to provide a framework for generating models
      relating to the specific and common sources of variation in the metabolite
      concentrations and protein abundances that can be directly related to the disease
      model. Multiple correlations between metabolites and proteins were found,
      including associations between serotransferrin precursor and both tyrosine and 3
      D-hydroxybutyrate. Additionally, a correlation between decreased concentration of
      tyrosine and increased presence of gelsolin was also observed. This approach can
      provide enhanced recovery of combination candidate biomarkers across multi-omic
      platforms, thus, enhancing understanding of in vivo model systems studied by
      multiple omic technologies.

PMID- 17022636
TI  - Proteomic analysis of the genotoxicant methylazoxymethanol (MAM)-induced changes
      in the developing cerebellum.
AB  - The genotoxicant methylazoxymethanol (MAM) is a widely used developmental
      neurotoxin, and its glucoside is an etiological factor for western Pacific
      amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS/PDC).
      Identification of global protein expression changes that occur in response to MAM
      in the developing cerebellum could provide valuable insight into the potential
      mechanisms involved in the neurodegeneration process. We have utilized
      fluorescence 2-dimensional differential gel electrophoresis (2D-DIGE), to
      determine the protein expression changes that occur during normal cerebellar
      development and in response to MAM. Three day-old postnatal C57BL/6 mice (PND3)
      received a single injection of MAM, and the cerebella of postnatal day 4 (PND4)
      and day 22 (PND22) were analyzed. Approximately, 1400 unique spots were matched
      and quantified in all samples. Comparison of PND4 and PND22 developing cerebellum
      showed that a significant fraction of the proteome (approximately 68%) changes at
      this stage. The immediate response of the developing cerebellum to MAM was
      minimal (approximately 10%). However, significant differences (27%) were noted 14
      days after MAM exposure. In contrast, the transcriptome changes were more
      pronounced at 24 h compared to 14 days. MAM targeted several proteins networks
      including transport (e.g., alpha-synuclein), cytoskeletal (e.g., beta-tubulin,
      vimentin), and mitochondrial (e.g., Atp5b) proteins. Immunochemistry confirmed
      several of the changes in protein expression (alpha-synuclein). Comparison with
      gene expression changes revealed that the temporal changes observed in the
      transcriptome and proteome are not correlative. These studies demonstrate for the
      first time the potential networks involved during neuronal development and
      neurodegenerative processes that are perturbed by MAM.

PMID- 17022637
TI  - Proteomics characterization of protein adsorption onto hemodialysis membranes.
AB  - Protein-adsorptive properties are a key feature of membranes used for
      hemodialysis treatment. Protein adsorption is vital to the biocompatibility of a
      membrane material and influences membrane's performance. The object of the
      present study is to investigate membrane biocompatibility by correlating the
      adsorbed proteome repertoire with structural feature of the membrane surfaces.
      Minidialyzers of identical structural characteristics composed of either
      cellulose diacetate or ethylenevinyl alcohol materials were employed to develop
      an ex vivo apparatus to investigate protein adsorption. Adsorbed proteins were
      eluted by a strong chaotropic buffer condition and investigated by 2-DE coupled
      to both MALDI-TOF mass spectrometry (MS) mass fingerprinting and fragmentation
      analysis on a nanoLC-MS/MS hybrid instrument. Membrane surface characterization
      included evaluation of roughness (atomic force microscopy), elemental chemical
      composition (X-ray-photoelectron-spectroscopy), and hydrophilicity (pulsed
      nuclear magnetic resonance). The present study identifies a number of different
      proteins as common or characteristic of filter material interaction, showing that
      proteomic techniques are a promising approach for the investigation of proteins
      surface-adsorbed onto hemodialysis membrane. Proteomic analysis enables the
      characterization of protein layers of unknown composition.

PMID- 17022638
TI  - An integrated metabonomic approach to describe temporal metabolic disregulation
      induced in the rat by the model hepatotoxin allyl formate.
AB  - The time-related metabolic events in rat liver, plasma, and urine following
      hepatotoxic insult with allyl formate (75 mg/kg) were studied using a combination
      of high-resolution liquid state and magic angle spinning (MAS) nuclear magnetic
      resonance (NMR) spectroscopic methods together with pattern recognition analysis.
      The metabonomics results were compared with the results of conventional plasma
      chemistry and histopathological assessments of liver damage. Various degrees of
      liver damage were observed in different animals, and this variation was reflected
      in all of the analyses. Furthermore, each analysis revealed a high degree of
      functional and structural recovery by the end of the study. The allyl formate
      induced changes included hepatocellular necrosis, hepatic lipidosis, decreased
      liver glycogen and glucose, decreased plasma lipids, increased plasma creatine
      and tyrosine, increased urinary taurine and creatine, and decreased urinary TCA
      cycle intermediates. The observed reductions in hepatic glycogen and glucose
      suggest increased glucose utilization and are consistent with the expected
      depletion of hepatic ATP following mitochondrial impairment, assuming that there
      is a consequent increase in energy production from glycolysis. The increase in
      plasma tyrosine is consistent with impaired protein synthesis, a known
      consequence of ATP depletion. Partial least squares-based cross-correlation of
      the variation in the liver and plasma NMR profiles indicated that the allyl
      formate-induced increase in liver lipids correlated with the decrease in plasma
      lipids. This suggests disruption in lipid transport from the liver to plasma,
      which could arise through impaired apolipoprotein synthesis, as with ethionine.

PMID- 17022639
TI  - Characterization of apolipoprotein M isoforms in low-density lipoprotein.
AB  - Apo M is a recently discovered human lipoprotein thought to be involved in the
      metabolism of lipids and lipoprotein particles. Here, a proteomic approach was
      applied to examine the glycosylation pattern of apo M in human LDL. We treated
      LDL proteins with N-glycosidase or neuraminidase, studied mobility shifts of Apo
      M by two-dimensional gel electrophoresis, and different isoforms were then
      identified with mass spectrometry. This way, we demonstrated the presence of five
      isoforms of apo M in LDL: three that are both N-glycosylated and sialylated, one
      that is N-glycosylated but not sialylated, and one that is neither N-glycosylated
      nor sialylated. As judged from the examination of LDL from 20 healthy human
      subjects, the three N-glycosylated and sialylated forms are most abundant (80
      100% of the total apo M in LDL) whereas the unsialylated and unglycosylated
      variants constitute at most 20%. Comparative analysis showed that the same five
      isoforms of apo M are also present in HDL. Further studies aiming at elucidating
      the role of apo M in health and disease will have to take this polymorphism of
      apo M proteins into account.

PMID- 17022640
TI  - Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular
      carcinoma: a glycoproteomic approach.
AB  - Increased serum haptoglobin concentration and changes in its glycosylation have
      been reported in certain cancer types. Information for hepatocellular carcinoma
      (HCC) has not yet been available. In this study, we aimed to carry out a
      systematic analysis of serum concentrations of haptoglobin (Hp) and its
      glycoforms in the patients with HCC and noncancer patients only with chronic
      liver diseases (CLD) and to examine their clinical values. This study was divided
      into two major parts, (1) measurement of serum Hp concentration, and
      investigation of its value in the diagnosis of HCC, and (2) quantitative analysis
      of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by
      using lectin affinity purification and 2D gel electrophoresis and investigation
      of their relationships with tumor stage. The concentrations of serum Hp in HCC
      patients were significantly higher than those in noncancer patients with CLD.
      With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic
      regression (LR) model was developed from the training data set and used to
      classify the validation cases. At a specificity of 95%, the sensitivity for HCC
      detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S
      Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests
      that purification of S-Hp and F-Hp could enrich the glycosylation variants
      associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18
      glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated
      fucosylated and hyposialylated fucosylated species was found in the HCC patients.
      Serum concentrations of these glycoproteins were significantly higher in the
      patients with advanced tumors, suggesting their tumor-specific nature. We have
      shown that serum Hp is a potential biomarker in the diagnosis of HCC. The
      combined use of Hp and AFP could greatly improve the diagnostic accuracy. A
      unique pattern of Hp glycoforms with altered sialylation and fucosylation is
      specific to HCC and associated tumor progression.

PMID- 17022641
TI  - Differential analysis of membrane proteins in mouse fore- and hindbrain using a
      label-free approach.
AB  - The ability to quantitatively compare protein levels across different regions of
      the brain to identify disease mechanisms remains a fundamental research
      challenge. It requires both a robust method to efficiently isolate proteins from
      small amounts of tissue and a differential technique that provides a sensitive
      and comprehensive analysis of these proteins. Here, we describe a proteomic
      approach for the quantitative mapping of membrane proteins between mouse fore-
      and hindbrain regions. The approach focuses primarily on a recently developed
      method for the fractionation of membranes and on-membrane protein digestion, but
      incorporates off-line SCX-fractionation of the peptide mixture and nano-LC-MS/MS
      analysis using an LTQ-FT-ICR instrument as part of the analytical method.
      Comparison of mass spectral peak intensities between samples, mapping of peaks to
      peptides and protein sequences, and statistical analysis were performed using in
      house differential analysis software (DAS). In total, 1213 proteins were
      identified and 967 were quantified; 81% of the identified proteins were known
      membrane proteins and 38% of the protein sequences were predicted to contain
      transmembrane helices. Although this paper focuses primarily on characterizing
      the efficiency of this purification method from a typical sample set, for many of
      the quantified proteins such as glutamate receptors, GABA receptors, calcium
      channel subunits, and ATPases, the observed ratios of protein abundance were in
      good agreement with the known mRNA expression levels and/or intensities of
      immunostaining in rostral and caudal regions of murine brain. This suggests that
      the approach would be well-suited for incorporation in more rigorous, larger
      scale quantitative analysis designed to achieve biological significance.

PMID- 17022642
TI  - Detection of noncovalent complexes in biological samples by intensity fading and
      high-mass detection MALDI-TOF mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has not yet
      contributed widely to the study of intact noncovalent biomolecular complexes,
      because MALDI is known to cause dissociation of the interaction partners and
      induce formation of nonspecific aggregates. Here, we present a new strategy to
      circumvent this problem. It is based on intensity fading (in the low m/z range)
      and high-mass detection MALDI mass spectrometry (MS), using a cryodetector (in
      the high m/z range), with and without chemical cross-linking of the interaction
      partners. The study focuses on noncovalent interactions between the human enzyme
      carboxypeptidase A (hCPA) and three protease inhibitors (PCI, TCI, and LCI)
      present in heterogeneous mixtures of other nonbinding molecules derived from a
      biological source, an extract from leech (Hirudo medicinalis). Another example
      involves an extract of the sea anemone Stichodactyla helianthus, which is used
      without previous fractionation to detect the specific complex between the enzyme
      trypsin and the endogenous SphI-1 inhibitor. The results give insight into the
      mechanism of intensity fading MS and demonstrate that the specificity of binding
      is greatly favored when the overall concentrations of the analytes (nonbinding
      molecules, protease inhibitor and target enzyme) present in a biological sample
      of interest are kept at low concentrations, in the sub-micromolar range. Higher
      concentrations may lead to unspecific interactions and the formation of
      aggregates both during the MALDI process and during reaction with the cross
      linking reagents. This strategy is expected to advance the field of high
      throughput affinity-based approaches, by taking advantage of a new generation of
      high mass detectors for MALDI-TOF instruments.

PMID- 17022643
TI  - A proteomic approach toward the selection of proteins with enhanced intrinsic
      conformational stability.
AB  - A detailed understanding of the molecular basis of protein folding and stability
      determinants partly relies on the study of proteins with enhanced conformational
      stability properties, such as those from thermophilic organisms. In this study,
      we set up a methodology aiming at identifying the subset of cytosolic hyperstable
      proteins using Sulfurispharea sp., a hyperthermophilic archaeon, able to grow
      between 70 and 97 degrees C, as a model organism. We have thermally and
      chemically perturbed the cytosolic proteome as a function of time (up to 96 h
      incubation at 90 degrees C), and proceeded with analysis of the remaining
      proteins by combining one- and two-dimensional gel electrophoresis, liquid
      chromatography fractionation, and protein identification by N-terminal sequencing
      and mass spectrometry methods. In total, 14 proteins with enhanced stabilities
      which are involved in key cellular processes such as detoxification, nucleic acid
      processing, and energy metabolism were identified including a superoxide
      dismutase, a peroxiredoxin, and a ferredoxin. We demonstrate that these proteins
      are biologically active after extensive thermal treatment of the proteome. The
      relevance of these and other targets is discussed in terms of the organism's
      ecology. This work thus illustrates an experimental approach aimed at mining a
      proteome for hyperstable proteins, a valuable tool for target selection in
      protein stability and structural studies.

PMID- 17022644
TI  - Quantitative proteomic and genomic profiling reveals metastasis-related protein
      expression patterns in gastric cancer cells.
AB  - Gastric cancer is a leading cause of death worldwide, and patients have an
      overall 5-year survival rate of less than 10%. Using quantitative proteomic
      techniques together with microarray chips, we have established comprehensive
      proteome and transcriptome profiles of the metastatic gastric cancer TMC-1 cells
      and the noninvasive gastric cancer SC-M1 cell. Our qualitative protein profiling
      strategy offers the first comprehensive analysis of the gastric cancer cell
      proteome, identifying 926 and 909 proteins from SC-M1 and TMC-1 cells,
      respectively. Cleavable isotope-coded affinity tagging analysis allows
      quantitation of a total of 559 proteins (with a protein false-positive rate of
      <0.005), and 240 proteins were differentially expressed (>1.3-fold) between the
      SC-M1 and TMC-1 cells. We identified numerous proteins not previously associated
      with gastric cancer. Notably, a large subset of differentially expressed proteins
      was associated with tumor metastasis, including proteins functioning in cell-cell
      and cell-extracellular matrix (cell-ECM) adhesion, cell motility, proliferation,
      and tumor immunity. Gene expression profiling by DNA microarray revealed
      differential expression (of >2-fold) of about 1000 genes. The weak correlation
      observed between protein and mRNA profiles highlights the important
      complementarities of DNA microarray and proteomics approaches. These comparative
      data enabled us to map the disease-perturbed cell-cell and cell-ECM adhesion and
      Rho GTPase-mediated cytoskeletal pathways. Further validation of a subset of
      genes suggests the potential use of vimentin and galectin 1 as markers for
      metastasis. We demonstrate that combining proteomic and genomic approaches not
      only provides a rapid, robust, and sensitive platform to elucidate the molecular
      mechanisms underlying gastric cancer metastasis but also may identify candidate
      diagnostic markers and therapeutic targets.

PMID- 17022645
TI  - Proteomics-based strategy to identify biomarkers and pharmacological targets in
      leukemias with t(4;11) translocations.
AB  - Translocations and other aberrations involving the MLL (mixed lineage leukemia)
      gene result in aggressive forms of leukemias. Heterogeneity in partner genes, in
      chromosomal breakpoints, in MLL itself, and in the different partner genes
      results in heterogeneous fusion transcripts that can be alternatively spliced,
      which complicates deciphering a unifying mechanism of leukemogenesis. However,
      recent microarray studies completed with clinical leukemia specimens have
      uncovered several distinct mRNA signatures within MLL leukemia that differ from
      other types of leukemia. A global proteomics strategy using MV4-11 and RS4:11
      cells in culture was employed to investigate possible protein signatures common
      to different MLL leukemias and to identify disease biomarkers and protein targets
      for pharmacological intervention. Initial proteomics screening experiments with
      two-dimensional differential in-gel electrophoresis revealed heat shock protein
      90 alpha (HSP90alpha) as a potential target for pharmacological inhibition and
      nucleoside diphosphate kinase (nm23) as a biomarker for measuring treatment
      efficacy. Using a modified stable isotope labeling of amino acids in cell culture
      (SILAC) approach, coupled with two-dimensional liquid chromatography tandem mass
      spectrometry (2D-LC-MS/MS), changes in abundance for over 500 proteins were
      measured. In addition, decreased expression of the novel biomarker nm23 was
      observed during HSP90 inhibition with 17-allylamino-17-demethoxygeldanamycin (17
      AAG) in the MV4-11 cell line. The present study validates the use of a global
      proteomics strategy to uncover novel biomarkers and pharmacological targets for
      leukemias with MLL translocations. Additionally, several proteins were found to
      be expressed in concordance with microarray studies of mRNA expression in
      specimens from patients showing the value in comparing mRNA transcript and
      proteomic profiles. This work represents one of the most comprehensive proteomics
      screens of MLL leukemias that have been conducted to date.

PMID- 17022646
TI  - The proteomic reactor: a microfluidic device for processing minute amounts of
      protein prior to mass spectrometry analysis.
AB  - Gel-free proteomics has emerged as a complement to conventional gel-based
      proteomics. Gel-free approaches focus on peptide or protein fractionation, but
      they do not address the efficiency of protein processing. We report the
      development of a microfluidic proteomic reactor that greatly simplifies the
      processing of complex proteomic samples by combining multiple proteomic steps.
      Rapid extraction and enrichment of proteins from complex proteomic samples or
      directly from cells are readily performed on the reactor. Furthermore, chemical
      and enzymatic treatments of proteins are performed in 50 nL effective volume,
      which results in an increased number of generated peptides. The products are
      compatible with mass spectrometry. We demonstrated that the proteomic reactor is
      at least 10 times more sensitive than current gel-free methodologies with one
      protein identified per 440 pg of protein lysate injected on the reactor.
      Furthermore, as little as 300 cells can be directly introduced on the proteomic
      reactor and analyzed by mass spectrometry.

PMID- 17022647
TI  - Proteome analysis of Myxococcus xanthus by off-line two-dimensional
      chromatographic separation using monolithic poly-(styrene-divinylbenzene) columns
      combined with ion-trap tandem mass spectrometry.
AB  - Myxobacteria are potent producers of secondary metabolites exhibiting diverse
      biological activities and pharmacological potential. The proteome of Myxococcus
      xanthus DK1622 was characterized by two-dimensional chromatographic separation of
      tryptic peptides from a lysate followed by tandem mass spectrometric
      identification. The high degree of orthogonality of the separation system
      employing polymer-based strong cation-exchange and monolithic reversed-phase
      stationary phases was clearly demonstrated. Upon automated database searching,
      1312 unique peptides were identified, which were associated with 631 unique
      proteins. High-molecular polyketide synthetases and nonribosomal peptide
      synthetases, known to be involved in the biosynthesis of various secondary
      metabolites, were readily detected. Besides the identification of gene products
      associated with the production of known secondary metabolites, proteins could
      also be identified for six gene clusters, for which no biosynthetic product has
      been known so far.

PMID- 17022648
TI  - Identification of glycoproteins in human cerebrospinal fluid with a complementary
      proteomic approach.
AB  - Biomarkers are pressingly needed to assist with the clinical diagnosis of
      neurodegenerative diseases and/or the monitoring of disease progression.
      Glycoproteins are enriched in bodily fluids such as human cerebrospinal fluid
      (CSF), an ideal source for discovering biomarkers due to its proximity to the
      central nervous system (CNS), and consequently can serve as diagnostic and/or
      therapeutic markers for CNS diseases. We report here an in-depth identification
      of glycoproteins in human CSF using a complementary proteomic approach which
      integrated hydrazide chemistry and lectin affinity column for glycoprotein
      enrichment, followed by multidimensional chromatography separation and tandem
      mass spectrometric analysis. Using stringent criteria, a total of 216
      glycoproteins, including many low-abundance proteins, was identified with high
      confidence. Approximately one-third of these proteins was already known to be
      relevant to the CNS structurally or functionally. This investigation, for the
      first time, not only categorized many glycoproteins in human CSF but also
      expanded the existing overall CSF protein database.

PMID- 17022649
TI  - Susceptibility of human metabolic phenotypes to dietary modulation.
AB  - Dietary composition has been shown to influence metabolism and to impact on the
      prevalence and risk for certain diseases, but hitherto, there have been no
      systematic studies on the effects of dietary modulation of human metabolic
      phenotype (metabotype). Here, we have applied 1H NMR spectroscopy in combination
      with multivariate statistical analysis to characterize the effects of three
      diets: "vegetarian", "low meat", and "high meat" on the metabotype signature of
      human participants. Twelve healthy male participants (age range of 25-74 years)
      consumed each of these diets, in a randomized order, for continuous 15-day
      periods with an intervening washout period between each diet of 7 days duration.
      Each participant provided three consecutive 24-hour urine collections on days 13,
      14, and 15 of each dietary period, and 1H NMR spectra were acquired on all
      samples. Pattern recognition analysis allowed differentiation of the
      characteristic metabolic signatures of the diets with creatine, carnitine,
      acetylcarnitine, and trimethylamine-N-oxide (TMAO) being elevated in the high
      meat consumption period. Application of orthogonal projection to latent structure
      discriminant analysis (O-PLS-DA) allowed the low-meat diet and vegetarian diet
      signatures to be characterized, and p-hydroxyphenylacetate (a microbial mammalian
      cometabolite) was higher in the vegetarian than meat diet samples, signaling an
      alteration of the bacterial composition or metabolism in response to diet. This
      work shows the potential for the routine use of metabonomics in nutritional and
      epidemiological studies, in characterizing and predicting the metabolic effects
      and the influence of diet on human metabotypes.

PMID- 17022650
TI  - Improved immobilized metal affinity chromatography for large-scale
      phosphoproteomics applications.
AB  - Dysregulated protein phosphorylation is a primary culprit in multiple
      physiopathological states. Hence, although analysis of signaling cascades on a
      proteome-wide scale would provide significant insight into both normal and
      aberrant cellular function, such studies are simultaneously limited by sheer
      biological complexity and concentration dynamic range. In principle, immobilized
      metal affinity chromatography (IMAC) represents an ideal enrichment method for
      phosphoproteomics. However, anecdotal evidence suggests that this technique is
      not widely and successfully applied beyond analysis of simple standards, gel
      bands, and targeted protein immunoprecipitations. Here, we report significant
      improvements in IMAC-based methodology for enrichment of phosphopeptides from
      complex biological mixtures. Moreover, we provide detailed explanation for key
      variables that in our hands most influenced the outcome of these experiments. Our
      results indicate 5- to 10-fold improvement in recovery of singly- and multiply
      phosphorylated peptide standards in addition to significant improvement in the
      number of high-confidence phosphopeptide sequence assignments from global
      analysis of cellular lysate. In addition, we quantitatively track phosphopeptide
      recovery as a function of phosphorylation state, and provide guidance for
      impedance-matching IMAC column capacity with anticipated phosphopeptide content
      of complex mixtures. Finally, we demonstrate that our improved methodology
      provides for identification of phosphopeptide distributions that closely mimic
      physiological conditions.

PMID- 17022651
TI  - A new computer program (GlycoX) to determine simultaneously the glycosylation
      sites and oligosaccharide heterogeneity of glycoproteins.
AB  - A new computer program, GlycoX, was developed to aid in the determination of the
      glycosylation sites and oligosaccharide heterogeneity in glycoproteins. After
      digestion with the nonspecific protease, each glycan at a specific glycosylation
      site contains a small peptide tag that identifies the location of the glycan.
      GlycoX was developed in MATLAB requiring the entry of the exact masses of the
      glycopeptide and the glycan spectra in the form of a mass-intensity table and
      taking advantage of the accurate mass capability of the mass analyzer, in this
      case a Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer. This
      program computes not only the glycosylation site but also the composition of the
      glycans at each site. Several glycoproteins were used to determine the efficacy
      of GlycoX. These glycoproteins range from the simple, with one site of
      glycosylation, to the more complex, with multiple (three) sites of glycosylation.
      The results obtained using the computer program were the same as those determined
      manually. Model glycoproteins yielded the correct results, and new glycoproteins
      with unknown glycosylation were examined with the site of glycosylation and the
      corresponding glycans determined. Furthermore, other functions in GlycoX,
      including an auto-isotope filter to identify monoisotopic peaks and an
      oligosaccharide calculator to obtain the oligosaccharide composition, are
      demonstrated.

PMID- 17022652
TI  - Proteomic analysis of the silkworm (Bombyx mori L.) hemolymph during
      developmental stage.
AB  - We utilized the proteomic approach to investigate the proteome of the fifth
      instar hemolymph during growth and development, and to improve the understanding
      of this important bioprocess and gene expression situation. A total of 25 microL
      of hemolymph was used for 2D analysis, and the separated proteins were visualized
      by silver staining and analyzed using the ImageMaster 2D software. The report
      showed as many as 241 of protein spots were expressed in the beginning of the
      fifth instar. Among them, most were concentrated in pI 3.5-6.5, which reached 76%
      of the total protein spots. As for the protein molecular sizes, 182 protein spots
      concentrated between 35 and 90 kDa, which comes to 75% of the total spots. When
      the larvae grow to the seventh day (total fifth instar duration was 9 days), 298
      protein spots were visualized through 2D electrophoresis. Fifty-seven spots were
      newly expressed compared to the image of the first day in fifth instar. The
      results implied that these proteins are related to biosynthesis of silk protein
      and metamorphosis preparation from larva to pupa. In total, 19 protein spots
      including 6 special spots expressed in seventh day were analyzed through MALDI
      TOF-MS. The relations between proteins and growth and development of silkworm
      were discussed.

PMID- 17022653
TI  - Proteomics analysis reveals insight into the mechanism of H-Ras-mediated
      transformation.
AB  - We implemented a proteomics approach to the systematical analysis of the
      alterations in the proteome of NIH3T3 cells transformed by oncogenic H-RasV12.
      Forty-four proteins associated with Ras-mediated transformation have been
      identified, and 28 proteins were not previously reported. RT-PCR analysis showed
      that approximately 44% of target proteins identified showed concomitant changes
      in mRNA abundance. A principal finding was the up-regulation of gankyrin, which
      was the first evidence to show that gankyrin pathway was implicated in Ras
      activated transformation.

PMID- 17022654
TI  - Simple urinary sample preparation for proteomic analysis.
AB  - Since the completion of the human genome sequence, attention has now focused on
      establishing reference maps of body fluids such as plasma and urine for detecting
      diagnostic markers of disease. Although some progress has been made, challenges
      still remain in the development of an optimal sample preparation method for
      proteomic analysis of urine. We have developed a simple and efficient urine
      preparation method for two-dimensional (2-D) gel electrophoresis which involves
      precipitation of proteins with simultaneous desalting. Acetonitrile precipitation
      produced 2-D gel separations with the highest resolution and the greatest number
      of protein spots compared to precipitation by other organic solvents. The method
      was applied to observe changes in the urinary proteome over a 6 week period and
      to establish a reference map of a healthy subject. A total of 339 proteins from
      159 genes was identified from healthy male urine by peptide mass fingerprinting.
      The profiles of the urinary proteome at three times in 1 day and on four
      different days were compared and were found to vary in number and spatial
      location of the proteins on the map. The method was also shown to be applicable
      to the higher concentrations of protein found in the urine of an ovarian cancer
      subject. We have developed a facile and robust method for preparing urine for 2-D
      gels that will encourage further use of urine.

PMID- 17022655
TI  - Proteomic studies of the intrinsically unstructured mammalian proteome.
AB  - Intrinsically unstructured proteins (IUPs) represent an important class of
      proteins primarily involved in cellular signaling and regulation. The aim of this
      study was to develop methodology for the enrichment and identification of IUPs.
      We show that heat treatment of NIH3T3 mouse fibroblast cell extracts at 98
      degrees C selects for IUPs. The majority of these IUPs were cytosolic or nuclear
      proteins involved in cell signaling or regulation. These studies represent the
      first large-scale experimental investigation of the intrinsically unstructured
      mammalian proteome.

PMID- 17022656
TI  - GAPP: a fully automated software for the confident identification of human
      peptides from tandem mass spectra.
AB  - This paper introduces the genome annotating proteomic pipeline (GAPP), a totally
      automated publicly available software pipeline for the identification of peptides
      and proteins from human proteomic tandem mass spectrometry data. The pipeline
      takes as its input a series of MS/MS peak lists from a given experimental sample
      and produces a series of database entries corresponding to the peptides observed
      within the sample, along with related confidence scores. The pipeline is capable
      of finding any peptides expected, including those that cross intron-exon
      boundaries, and those due to single nucleotide polymorphisms (SNPs), alternate
      splicing, and post-translational modifications (PTMs). GAPP can therefore be used
      to re-annotate genomes, and this is supported through the inclusion of a
      Distributed Annotation System (DAS) server, which allows the peptides identified
      by the pipeline to be displayed in their genomic context within the Ensembl
      genome browser. GAPP is freely available via the web, at www. gapp.info.

PMID- 17022657
TI  - Novel strategy of high-abundance protein depletion using multidimensional liquid
      chromatography.
AB  - In this study, for the first time, a comprehensive two-dimensional (2D) liquid
      phase separation system, coupling strong cation exchange chromatography (SCX) to
      reversed-phase high performance liquid chromatography (RPLC), instead of
      specificity depletion method, was developed at the intact protein level for
      depletion of high-abundance proteins from rat liver. Proteins were
      prefractionated by SCX in the first dimensional separation, followed by RPLC with
      high resolution separation. UV absorption intensity was used to differentiate
      high-abundance proteins. The proteins with the absorbance intensity above 0.1 AU
      were defined as high abundance proteins and depleted. After removal of high
      abundance proteins; other proteins were pooled, digested, and subsequently
      separated by capillary liquid chromatography coupled with MALDI-TOF/TOF mass
      spectrometry analysis. The high efficiency of the strategy was demonstrated by
      analyzing the soluble protein extracted from rat liver tissue. In total, 77 high
      abundance proteins were depleted in one experiment flow. The ratio of depleted
      content of high-abundance proteins to that of total proteins was about 34.5%. In
      total, 1530 proteins were identified using the depletion strategy. Quantitative
      estimation of high-abundance proteins through liquid chromatography combined with
      UV absorption spectra was achieved. On the basis of the reproducible experimental
      results, a rapid and high-throughput depletion protocol was put forward. Along
      with depletion of the most (79.1%) high-abundance proteins and the separation of
      digested peptides, the total separation time could be less than 30 h. This
      strategy has no bias for depleting high-abundance proteins and enhances the
      number of identified proteins; therefore, it can be widely used in the global
      proteins analysis.

PMID- 17022658
TI  - Improved mass spectrometric proteomic profiling of the secretome of rat vascular
      endothelial cells.
AB  - Serum albumin contamination of cells cultured in vitro significantly impedes the
      mass spectrometric analysis of proteins secreted by the cells. Here we report a
      novel washing and culturing technique for rat vascular endothelial cells that
      considerably reduces the concentration of the commonly used additive for cell
      culture, bovine serum albumin (BSA), in the secretome of these cells. Cells are
      rinsed stringently and cultured for 24 h in serum-free media without appreciably
      impeding cell growth or viability. The percentage of BSA scans identified by
      tandem mass spectrometry (LC-MS/MS) in stringently rinsed cells (average 13.2%)
      was significantly lower than either the moderately rinsed or no rinse cell
      treatments (average 35.2% and 45.2% respectively). Furthermore, the stringent
      wash treatment allowed the confident identification of a larger portion of the
      secretome of rat endothelial cells by LC-MS/MS.

PMID- 17022659
TI  - Unravelling carbon metabolism in anaerobic cellulolytic bacteria.
AB  - Carbon metabolism in anaerobic cellulolytic bacteria has been investigated
      essentially in Clostridium thermocellum, Clostridium cellulolyticum, Fibrobacter
      succinogenes, Ruminococcus flavefaciens, and Ruminococcus albus. While cellulose
      depolymerization into soluble sugars by various cellulases is undoubtedly the
      first step in bacterial metabolisation of cellulose, it is not the only one to
      consider. Among anaerobic cellulolytic bacteria, C. cellulolyticum has been
      investigated metabolically the most in the past few years. Summarizing metabolic
      flux analyses in continuous culture using either cellobiose (a soluble
      cellodextrin resulting from cellulose hydrolysis) or cellulose (an insoluble
      biopolymer), this review aims to stress the importance of the insoluble nature of
      a carbon source on bacterial metabolism. Furthermore, some general and specific
      traits of anaerobic cellulolytic bacteria trends, namely, the importance and
      benefits of (i) cellodextrins with degree of polymerization higher than 2, (ii)
      intracellular phosphorolytic cleavage, (iii) glycogen cycling on cell
      bioenergetics, and (iv) carbon overflows in regulation of carbon metabolism, as
      well as detrimental effects of (i) soluble sugars and (ii) acidic environment on
      bacterial growth. Future directions for improving bacterial cellulose degradation
      are discussed.

PMID- 17022660
TI  - Optimization of fed-batch Saccharomyces cerevisiae fermentation using dynamic
      flux balance models.
AB  - We developed a dynamic flux balance model for fed-batch Saccharomyces cerevisiae
      fermentation that couples a detailed steady-state description of primary carbon
      metabolism with dynamic mass balances on key extracellular species. Model-based
      dynamic optimization is performed to determine fed-batch operating policies that
      maximize ethanol productivity and/or ethanol yield on glucose. The initial volume
      and glucose concentrations, the feed flow rate and dissolved oxygen concentration
      profiles, and the final batch time are treated as decision variables in the
      dynamic optimization problem. Optimal solutions are generated to analyze the
      tradeoff between maximal productivity and yield objectives. We find that for both
      cases the prediction of a microaerobic region is significant. The optimization
      results are sensitive to network model parameters for the growth associated
      maintenance and P/O ratio. The results of our computational study motivate
      continued development of dynamic flux balance models and further exploration of
      their application to productivity optimization in biochemical reactors.

PMID- 17022661
TI  - Optimization of the human adenosine A2a receptor yields in Saccharomyces
      cerevisiae.
AB  - G-protein coupled receptors (GPCRs) have been implicated in many human diseases
      and have emerged as important drug targets. Despite their medical relevance,
      knowledge about GPCR structure is limited, mainly due to difficulties associated
      with producing large amounts of functional protein and isolating this protein in
      functional form. However, our previous results indicate that when the human
      adenosine A(2)a receptor (A(2)aR) is expressed in Saccharomyces cerevisiae, high
      yields can be achieved. In light of these initial results and in anticipation of
      future purification efforts, experiments were conducted to optimize the system
      for maximum total protein yield. Emphasis was placed on not only producing large
      quantities of A(2)aR in each cell but also achieving high cell density in batch
      culture. Therefore, temperature, media pH, inducer concentration in the media,
      and induction cell density were tested for their effects on both cell growth (as
      measured by optical density, OD(600)) and per cell A(2)aR expression levels. For
      these studies, the A(2)aR expression levels were determined using a previously
      described A(2)aR-green fluorescent protein (GFP) fusion, so that expression could
      be monitored by fluorescence. Overall the data indicate that at late times (
      approximately 60 h of expression) approximately 75% higher total batch protein
      yields can be achieved using lower expression temperatures or 60% higher using
      elevated induction cell density. The highest yields correspond to approximately
      28 mg per liter of culture of total A(2)aR. Amounts of functional receptor were
      shown to increase on a per cell basis by decreasing expression temperature up to
      25 h of expression, but at late time points ( approximately 60 h) functional
      yields did not appreciably improve. When compared to other reports of GPCR
      expression in yeast it is clear that this system is among those producing the
      highest GPCR protein yields per culture both before and after optimization.

PMID- 17022662
TI  - Localization effect on the metal biosorption capability of recombinant mammalian
      and fish metallothioneins in Escherichia coli.
AB  - In this study, we examined the expression of mammalian and fish metallothioneins
      (MTs) in Escherichia coli as a strategy to enhance metal biosorption efficiency
      of bacterial biosorbents for lead (Pb), copper (Cu), cadmium (Cd), and zinc (Zn).
      In addition, MT proteins were expressed in either the cytoplasmic or periplasmic
      compartment of host cells to explore the localization effect on metal
      biosorption. The results showed that MT expression led to a significant increase
      (5-210%) in overall biosorption efficiency (eta(ads)), especially for biosorption
      of Cd. The MT-driven improvement in metal biosorption relied more on the increase
      in the biosorption rates (r(2), a kinetic property) than on the equilibrium
      biosorption capacities (q(max), a thermodynamic property), despite a 10-45% and
      30-80% increase in q(max) of Cd and Zn, respectively. Periplasmic expression of
      MTs appeared to be more effective in facilitating the metal-binding ability than
      the cytoplasmlic MT expression. Notably, disparity of the impacts on biosorption
      ability was observed for the origin of MT proteins, as human MT (MT1A) was the
      most effective biosorption stimulator compared to MTs originating from mouse
      (MT1) and fish (OmMT). Moreover, the overall biosorption efficiency (eta(ads)) of
      the MT-expressing recombinant biosorbents was found to be adsorbate-dependent:
      the eta(ads) values decreased in the order of Cd > Cu > Zn > Pb.

PMID- 17022663
TI  - Construction and characterization of ack deleted mutant of Clostridium
      tyrobutyricum for enhanced butyric acid and hydrogen production.
AB  - Clostridium tyrobutyricum produces butyrate, acetate, H(2), and CO(2) as its main
      fermentation products from glucose and xylose. To improve butyric acid and
      hydrogen production, integrational mutagenesis was used to create a metabolically
      engineered mutant with inactivated ack gene, encoding acetate kinase (AK)
      associated with the acetate formation pathway. A non-replicative plasmid
      containing the acetate kinase gene (ack) fragment was constructed and introduced
      into C. tyrobutyricum by electroporation. Integration of the plasmid into the
      homologous region on the chromosome should inactivate the target ack gene and
      produce ack-deleted mutant, PAK-Em. Enzyme activity assays showed that the AK
      activity in PAK-Em decreased by approximately 50%; meanwhile,
      phosphotransacetylase (PTA) and hydrogenase activities each increased by
      approximately 40%. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) results showed that the expression of protein with approximately 32
      kDa molecular mass was reduced significantly in the mutant. Compared to the wild
      type, the mutant grew more slowly at pH 6.0 and 37 degrees C, with a lower
      specific growth rate of 0.14 h(-1) (vs 0.21 h(-1) for the wild type), likely due
      to the partially impaired PTA-AK pathway. However, the mutant produced 23.5% more
      butyrate (0.42 vs 0.34 g/g glucose) at a higher final concentration of 41.7 g/L
      (vs 19.98 g/L) as a result of its higher butyrate tolerance as indicated in the
      growth kinetics study using various intial concentrations of butyrate in the
      media. The mutant also produced 50% more hydrogen (0.024 g/g) from glucose than
      the wild type. Immobilized-cell fermentation of PAK-Em in a fibrous-bed
      bioreactor (FBB) further increased the final butyric acid concentration (50.1
      g/L) and the butyrate yield (0.45 g/g glucose). Furthermore, in the FBB
      fermentation at pH 5.0 with xylose as the substrate, only butyric acid was
      produced by the mutant, whereas the wild type produced large amounts of acetate
      (0.43 g/g xylose) and lactate (0.61 g/g xylose) and little butyrate (0.05 g/g
      xylose), indicating a dramatic metabolic pathway shift caused by the ack deletion
      in the mutant.

PMID- 17022664
TI  - Spectroscopic characterization and electrochemistry of poly(ethylene oxide)
      modified myoglobin in organic solvents.
AB  - Myoglobin (Mb) was chemically modified with activated poly(ethylene oxide) (PEO)
      (average molecular weight of 2000) to solubilize it in various organic solvents.
      UV-vis, circular dichroism, and Raman spectroscopy were used to characterize the
      structure correlated with the electron-transfer reactions of PEO-modified Mb (PEO
      Mb). Spectroscopic data indicated changes in heme coordination geometry for PEO
      Mb in various organic solvents that are different from that in water. The Raman
      spectrum showed the characteristics of PEO-Mb in PEO oligomer (average MW of 200)
      in the five-coordinate high-spin state, which facilitates fast electron-transfer
      reactions between protein and the glassy carbon electrode. These results suggest
      heme environment effects on the properties of proteins in organic solvents.

PMID- 17022665
TI  - Co2+, Cu2+, and Zn2+ accumulation by cyanobacterium Spirulina platensis.
AB  - The Spirulina platensis biomass was characterized for its metal accumulation as a
      function of pH, external metal concentration, equilibrium isotherms, kinetics,
      effect of co-ions under free (living cells, lyophilized, and oven-dried) and
      immobilized (Ca-alginate and polyacrylamide gel) conditions. The maximum metal
      biosorption by S. platensis biomass was observed at pH 6.0 with free and
      immobilized biomass. The studies on equilibrium isotherm experiments showed
      highest maximum metal loading by living cells (181.0 +/- 13.1 mg Co(2+)/g, 272.1
      +/- 29.4 mg Cu(2+)/g and 250.3 +/- 26.4 mg Zn(2+)/g) followed by lyophilized
      (79.7 +/- 9.6 mg Co(2+)/g, 250.0 +/- 22.4 mg Cu(2+)/g and 111.2 +/- 9.8 mg
      Zn(2+)/g) and oven-dried (25.9 +/- 1.9 mg Co(2+)/g, 160.0 +/- 14.2 mg Cu(2+)/g
      and 35.1 +/- 2.7 mg Zn(2+)/g) biomass of S. platensis on a dry weight basis. The
      polyacrylamide gel (PAG) immobilization of lyophilized biomass found to be
      superior over Ca-alginate (Ca-Alg) and did not interfere with the S. platensis
      biomass biosorption capacity, yielding 25% of metal loading after PAG entrapment.
      The time-dependent metal biosorption in both the free and immobilized form
      revealed existence of two phases involving an initial rapid phase (which lasted
      for 1-2 min) contributing 63-77% of total biosorption, followed by a slower phase
      that continued for 2 h. The metal elution studies conducted using various
      reagents showed more than 90% elution with mineral acids, calcium salts, and
      Na(2)EDTA with free (lyophilized or oven-dried) as well as immobilized biomass.
      The experiments conducted to examine the suitability of PAG-immobilized S.
      platensis biomass over multiple cycles of Co(2+), Cu(2+), and Zn(2+) sorption and
      elution showed that the same PAG cubes can be reused for at least seven cycles
      with high efficiency.

PMID- 17022666
TI  - Proteomic analysis for the assessment of different lots of fetal bovine serum as
      a raw material for cell culture. Part IV. Application of proteomics to the
      manufacture of biological drugs.
AB  - Fetal bovine serum (FBS) is the most widely used growth supplement for cell
      cultures, primarily because of its high levels of growth stimulatory factors and
      low levels of growth inhibitory factors. Maintaining successful and consistent
      cell fermentations can be difficult, as FBS is a complex natural product and may
      vary from lot to lot even from a single manufacturer. The quality and
      concentration of both bulk and specific proteins can affect cell growth. Quality
      control tools for FBS are relatively primitive and expensive given the complexity
      of the sample and the large amounts of FBS used. We undertook this study to
      examine whether proteomics could be used as a tool to analyze the variability of
      different fermentation processes. We hypothesized that inconsistent cell growth
      in fermentations could be due to the quality of FBS and that different lots of
      FBS had varying concentrations of proteins such as growth stimulatory factors,
      growth inhibitory factors, and/or other proteins that may correlate with cellular
      growth rate. To investigate whether this was the case, we grew three batches of
      adult retinal pigment epithelial cells (ARPE-19) using three different lots of
      fetal bovine serum (FBS-Ia, FBS-Ib, and FBS-II). We found that the growth rate of
      the culture was significantly and consistently higher in the FBS-II lot. To
      determine why the other lots promoted different growth properties, we used
      proteomic techniques to analyze the protein composition of the three lots. We
      then performed a time course study to monitor specific changes in individual
      proteins in the fermentation medium. The amount of several extracellular matrix
      and structural proteins, which are indicators of cell growth, increased over
      time. Alternatively, components supplied by the FBS addition, such as nutritional
      related and cell-spreading-related proteins, decreased over time.

PMID- 17022667
TI  - Asymmetric reduction of o-chloroacetophenone with Candida pseudotropicalis 104.
AB  - The asymmetric reduction of o-chloroacetophenone 1 with Candida pseudotropicalis
      104 produced the corresponding (S)-1-(2-chloro-phenyl)-ethanol 2 with the
      enantiomeric excess (ee >99%) without addition of any cosolvent. The cell could
      tolerate high ketone 1 concentration of 233.8 mmol/L (i.e., 36 g/L) with
      considerable reduction activity in this method. The product 2 concentration
      achieved 38.9 and 58.4 mmol/L with cells of 40 and 60 g(DCW) (dry cell weight)/L,
      respectively, in 24 h. The optimum reaction time, the effect of substrate
      concentration, cosubstrate type and concentration, and cell concentration in the
      reaction were investigated in this paper.

PMID- 17022668
TI  - Investigations of reaction kinetics for immobilized enzymes--identification of
      parameters in the presence of diffusion limitation.
AB  - A method is proposed for identification of kinetic parameters when diffusion of
      substrates is limiting in reactions catalyzed by immobilized enzymes. This method
      overcomes conventional sequential procedures, which assume immobilization does
      not affect the conformation of the enzyme and, thus, consider intrinsic and
      inherent kinetics to be the same. The coupled equations describing intraparticle
      mass transport are solved simultaneously using numerical methods and are used for
      direct estimation of kinetic parameters by fitting modeling results to time
      course measurements in a stirred tank reactor. While most traditional procedures
      were based on Michaelis-Menten kinetics, the method presented here is applicable
      to more complex kinetic mechanisms involving multiple state variables, such as
      ping-pong bi-bi. The method is applied to the kinetic resolution of (R/S)-1
      methoxy-2-propanol with vinyl acetate catalyzed by Candida antarctica lipase B. A
      mathematical model is developed consisting of irreversible ping-pong bi-bi
      kinetics, including competitive inhibition of both enantiomers. The kinetic
      model, which fits to experimental data over a wide range of both substrates (5
      95%) and temperatures (5-56 degrees C), is used for simulations to study typical
      behavior of immobilized enzyme systems.

PMID- 17022669
TI  - Effect of temperature and high pressure on the activity and mode of action of
      fungal pectin methyl esterase.
AB  - Pectin was de-esterified with purified recombinant Aspergillus aculeatus pectin
      methyl esterase (PME) during isothermal-isobaric treatments. By measuring the
      release of methanol as a function of treatment time, the rate of enzymatic pectin
      conversion was determined. Elevated temperature and pressure were found to
      stimulate PME activity. The highest rate of PME-catalyzed pectin de
      esterification was obtained when combining pressures in the range 200-300 MPa
      with temperatures in the range 50-55 degrees C. The mode of pectin de
      esterification was investigated by characterizing the pectin reaction products by
      enzymatic fingerprinting. No significant effect of increasing pressure (300 MPa)
      and/or temperature (50 degrees C) on the mode of pectin conversion was detected.

PMID- 17022670
TI  - Hydrolysis kinetics of trisaccharides consisting of glucose, galactose, and
      fructose residues in subcritical water.
AB  - The hydrolysis kinetics of trisaccharides consisting of glucose, galactose, and
      fructose residues with different glycosidic bonds, 1-kestose, d-melezitose, d
      raffinose, and lactosucrose, in subcritical water were conducted over the
      temperature range of 150-230 degrees C and at a constant pressure of 10 MPa. The
      hydrolysis of trisaccharides in subcritical water proceeded consecutively, i.e.,
      one cleavage of the two bonds antedated the other. The preceding cleavage was not
      expressed by the first-order kinetics, but by the kinetics considering the
      concentration of the acidic compounds, which were produced by the degradation of
      the constituent monosaccharides. The hydrolysis of the constituent disaccharides,
      except sucrose composed of the alpha-Glc-(1-->2)-beta-Fru bond, obeyed first
      order kinetics. All of the rate constants of the hydrolytic kinetics were
      determined, and the values were found to depend on the type of bond.

PMID- 17022671
TI  - Hydrogenogenic CO conversion in a moderately thermophilic (55 degrees C) sulfate
      fed gas lift reactor: competition for CO-derived H(2).
AB  - Thermophilic (55 degrees C) sulfate reduction in a gas lift reactor fed with CO
      gas as the sole electron donor was investigated. The reactor was inoculated with
      mesophilic granular sludge with a high activity of CO conversion to hydrogen and
      carbon dioxide at 55 degrees C. Strong competition for H(2) was observed between
      methanogens and sulfate reducers, while the homoacetogens present consumed only
      small amounts of H(2). The methanogens appeared to be more sensitive to pH and
      temperature shocks imposed to the reactor, but could not be completely
      eliminated. The fast growth rates of the methanogens (generation time of 4.5 h)
      enabled them to recover fast from shocks, and they rapidly consumed more than 90%
      of the CO-derived H(2). Nevertheless, steep increases in sulfide production in
      periods with low methane production suggests that once methanogenesis is
      eliminated, sulfate reduction with CO-rich gas as electron donor has great
      potential for thermophilic biodesulfurization.

PMID- 17022672
TI  - Development of a highly productive and scalable plasmid DNA production platform.
AB  - With the applications of DNA vaccines extending from infectious diseases to
      cancer, achieving the most efficient, reproducible, robust, scalable, and
      economical production of clinical grade plasmid DNA is paramount to the medical
      and commercial success of this novel vaccination paradigm. A first generation
      production process based on the cultivation of Escherichia coli in a chemically
      defined medium, employing a fed-batch strategy, delivered reasonable volumetric
      productivities (500-750 mg/L) and proved to perform very well across a wide range
      of E. coli constructs upon scale-up at industrial scale. However, the presence of
      monosodium glutamate (MSG) in the formulation of the cultivation and feed
      solution was found to be a potential cause of process variability. The
      development of a second generation process, based on a defined cultivation medium
      and feed solution excluding MSG, was undertaken. Optimization studies, employing
      a plasmid coding for the HIV gag protein, resulted in cultivation conditions that
      supported volumetric plasmid titers in excess of 1.2 g/L, while achieving
      specific yields ranging from 25 to 32 microg plasmid DNA/mg of dry cell weight.
      When used for the production of clinical supplies, this novel process
      demonstrated applicability to two other constructs upon scale-up in 2,000-L
      bioreactors. This second generation process proved to be scalable, robust, and
      highly productive.

PMID- 17022673
TI  - Purification of densonucleosis virus by tangential flow ultrafiltration.
AB  - Purification at commercial scale of viruses and virus vectors for gene therapy
      applications and viral vaccines is a major separations challenge. Tangential flow
      ultrafiltration has been developed for protein purification. Here tangential flow
      ultrafiltration of parvoviruses has been investigated. Because these virus
      particles are small (18-26 nm), removal of host cell proteins will be
      challenging. The results obtained here indicate that 30, 50, and 100 kDa
      membranes reject the virus particles, whereas 300 kDa membranes allow some virus
      particles to pass into the permeate. The decrease in permeate flux for the 300
      kDa ultrafiltration membrane is much greater than for the 30, 50, and 100 kDa
      membranes, indicating possible entrapment of virus particle in the membrane
      pores. The permeate flux and level of protein rejection is strongly affected by
      the cell culture growth medium. The results indicate that when developing a new
      process, it is essential that the cell culture and purification operations be
      developed in parallel.

PMID- 17022674
TI  - Lipase-mediated purification of methyl nonactate, an important natural product
      building block for diversity-oriented synthesis.
AB  - Methyl nonactate is a valuable starting material for the production of natural
      product-like combinatorial libraries and ketide amino acids, a series of novel
      conformationally constrained amino acid analogues. Fermentation of Streptomyces
      griseus generates high titers of macrotetrolide antibiotics from which methyl
      nonactate can be generated by methanolysis. Unfortunately, this approach
      generates mixtures of homologues that are not economically separable. We report a
      specific lipase-mediated hydrolysis of nonactate derivatives that discriminates
      between homologues and is the foundation of an economically tractable preparation
      of methyl nonactate in scale.

PMID- 17022675
TI  - Design of adsorptive columns for specific pathogen removal: application to
      staphylococcal enterotoxin B.
AB  - The removal of pathogens such as toxins, viruses, bacteria, and prions in human
      blood, mammalian cell culture media, fermentation broths, food items, and water
      streams has gained increasing importance in ensuring product safety and in
      combatting acts of terrorism. Adsorption processes can play an important role in
      removing such pathogens from solution without affecting other desirable
      components. Adsorptive columns that can remove specific families of pathogens
      would need to achieve a reduction of several logs in pathogen concentration. This
      requirement is much more stringent than the normal yield requirements associated
      with adsorptive separations aimed at product recovery and purification in a
      process stream. This paper considers the design of an adsorptive column aimed at
      reducing the concentration of infectious agents from a known volume of solution
      by several logs in a fixed amount of time. The general rate (GR) model of
      chromatography is used in the analysis, including all major transport and kinetic
      steps in the adsorption process. The theory, with no adjustable parameters, is
      shown to predict with great accuracy the effect of residence time on the log
      removal of staphylococcal enterotoxin B (SEB) from solution using an affinity
      resin with a small peptide (YYWLHH) that has been found to bind specifically to
      this toxin.

PMID- 17022676
TI  - Alkane utilization by Rhodococcus strain NTU-1 alone and in its natural
      association with Bacillus fusiformis L-1 and Ochrobactrum sp.
AB  - Linear (n-hexadecane) and branched (pristane) alkanes were degraded by a mixed
      culture isolated from an oil-contaminated field. The degradation was accompanied
      by formation of biofloccules. The culture was composed of Rhodococcus strain NTU
      1, Bacillus fusiformis L-1, and Ochrobactrum sp. Rhodococcus strain NTU-1 carried
      out the degradation of the alkane via a hydroxylase. Bacillus fusiformis L-1 and
      Ochrobactrum sp. did not degrade the alkanes but aided the flocculation by
      forming more rigid bacterial aggregates that enhanced the trapping of alkanes. In
      batch cultures, transformation and removal of the linear and branched alkanes was
      achieved within 66 h with more than 95% efficiency.

PMID- 17022677
TI  - Targeted oxygen delivery within hepatic hollow fiber bioreactors via
      supplementation of hemoglobin-based oxygen carriers.
AB  - Hepatic hollow fiber bioreactors are considered a promising class of
      bioartificial liver assist device (BLAD). Unfortunately, limited oxygen (O(2))
      transport to hepatocytes within this device hinders further development.
      Hepatocytes in vivo (in the liver sinusoid) experience a wide range of oxygen
      tensions (pO(2) = 25-70 mmHg), which is important for development of proper
      differentiated function (zonation). Previously, we observed that bovine red blood
      cell (bRBC) supplementation of the circulating media stream enhanced oxygenation
      of cultured C3A hepatoma cells compared to a culture with no O(2) carrier
      (Gordon, J.; Palmer, A. F. Artif. Cells, BloodSubstitutes, Biotechnol. 2006, 33
      (3), 297-306). Despite this success, the cells were not exposed to the desired in
      vivo O(2) spectrum (Sullivan, J.; Gordon, J.; Palmer, A. Biotechnol. Bioeng.
      2006, 93 (2) 306-317). We hypothesize that altering the kinetics of O(2)
      binding/release to/from hemoglobin-based O(2) carriers (HBOCs) could potentially
      target O(2) delivery to cell cultures. High P(50) (low O(2) affinity) HBOCs
      preferentially targeted O(2) delivery at high inlet pO(2) values. Conversely, low
      P(50) (high O(2) affinity) HBOCs targeted O(2) delivery at low inlet pO(2)
      values. Additionally, inlet pO(2), flow rate, and HBOC concentration were varied
      to find optimal bioreactor operating conditions. Our results demonstrate that
      HBOCs can enhance O(2) delivery to cultured hepatocytes, while exposing them to
      in vivo-like O(2) tensions, which is critical to create a fully functional BLAD.

PMID- 17022678
TI  - Micropatterning of porous silicon films by direct laser writing.
AB  - In this study, we demonstrate that porous silicon films can be ablated by the
      pulsed nitrogen laser of a commercial MALDI mass spectrometer. The extent of
      laser-induced ablation was found to depend on the doping level and surface
      chemistry of the porous silicon film. Using direct laser writing with or without
      a mask, micropatterns were generated on the porous silicon surface. These
      micropatterns were subsequently used to guide the growth of mammalian cells
      including neuroblastoma. Excellent selectivity of cell growth toward the laser
      ablated regions was established.

PMID- 17022679
TI  - Plasmid DNA delivery by D-alanine-deficient Listeria monocytogenes.
AB  - Optimal DNA vaccine efficacy requires circumventing several obstacles, including
      low immunogenicity, a need for adjuvant, and the costs of purifying injection
      grade plasmid DNA. Bacterial delivery of plasmid DNA may provide an efficient and
      low-cost alternative to plasmid purification and injection. Also, the bacterial
      vector may exhibit potential as an immune adjuvant in vivo. Thus, we elected to
      examine the use of cell-wall-deficient Listeria monocytogenes as a DNA delivery
      vehicle in vitro. First, the D-alanine-deficient (Deltadal-dat) L. monocytogenes
      strain DP-L3506, which undergoes autolysis inside eukaryotic host cells in the
      absence of D-alanine, was transformed with a plasmid encoding green fluorescent
      protein (GFP) under control of the CMV promoter (pAM-EGFP). Then COS-7 and MC57G
      cell lines were infected with the transformed DP-L3506 at various multiplicities
      of infection (MOI) in the presence or absence of D-alanine. Subsequent GFP
      expression was observed in both cell lines by 24 h post-infection with DP
      L3506(pAM-EGFP). Notably, no GFP positive cells were observed when D-alanine was
      omitted. Although transfection efficiency initially increased as a result of D
      alanine supplementation, high concentration or long-term supplementation led to
      sustained bacterial growth that killed the infected host cells, resulting in
      fewer GFP-expressing cells. Thus, efficient DNA delivery by transformed bacteria
      must balance bacterial invasion and survival with target cell health and
      survival.

PMID- 17022680
TI  - Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for
      articular cartilage.
AB  - The prevalence of suboptimal outcome for surgical interventions in the treatment
      of full-thickness articular cartilage damage suggests that there is scope for a
      materials-based strategy to deliver a more durable repair. Given that the
      superficial layer of articular cartilage creates and sustains the tribological
      function of synovial joints, it is logical that candidate materials should have
      surface viscoelastic properties that mimic native articular cartilage. The
      present paper describes force spectroscopy analysis by nano-indentation to
      measure the elastic modulus of the surface of a novel poly(vinyl alcohol)
      hydrogel with therapeutic potential as a joint implant. More than 1 order of
      magnitude decrease in the elastic modulus was detected after adsorption of a
      hyaluronic acid layer onto the hydrogel, bringing it very close to previously
      reported values for articular cartilage. Covalent derivatization of the hydrogel
      surface with fibronectin facilitated the adhesion and growth of cultured rat
      tibial condyle chondrocytes as evidenced morphologically and by the observance of
      metachromatic staining with toluidine blue dye. The present results indicate that
      hydrogel materials with potential therapeutic benefit for injured and diseased
      joints can be engineered with surfaces with biomechanical properties similar to
      those of native tissue and are accepted as such by their constituent cell type.

PMID- 17022681
TI  - Microengineered surface topography facilitates cell grafting from a prototype
      hydrogel wound dressing with antibacterial capability.
AB  - Skin wounds derive therapeutic benefit from redeployment of dermal tissues,
      whether as split-thickness allo- and autografts or as biological dressings
      comprising cultured cells. However, the clinical outcome is strongly influenced
      by the techniques used for cell/tissue grafting and also the microbiological
      status of the wound. Here we report that microtopography incorporated into the
      surface of a novel polymeric material, derivatized with fibronectin to promote
      attachment and encourage motility, improved the efficiency of cell transfer onto
      de-epithelialized human skin ex vivo. The microtopography had two functions,
      first as a conduit for migrating cells to cross between the vehicle and recipient
      surface and second to shield adherent cells from destruction by mechanical
      shearing during handling and application. Quantitative analysis showed that
      topographic projections (columns) rather than recesses (pits) in the hydrogel
      surface achieved the highest efficiency of cell transfer. In order to address the
      crucial relevance of microbiological contamination to the success of wound
      grafting, the effect of iodine on several common bacterial pathogens was examined
      using an XTT+C(Q10) kinetic cell viability assay. Increasing concentrations of
      iodine initially stressed and after 0.5% v/v were subsequently bacteriocidal for
      Gram-negative Pseudomonas aeruginosa and Escherichia coli and Gram-positive
      Bacillus subtillis and Staphylococcus aureus. Slightly higher doses of iodine
      (approx 1-1.5% v/v) were required to kill HaCaT cells outright, but for both pro-
      and eukaryotes the major determinant of cytotoxicity was absolute dose rather
      than duration of exposure. Iodine delivered by the hydrogel at low concentration
      was bacteriostatic but not apparently cytotoxic to epithelial cells as measured
      by MTT end-point cell viability assay. Zone of inhibition studies confirmed that
      bacteriocidal quantities of neomycin, phenol red, and silver could also be
      delivered using the same hydrogel. This research suggests that grafting cell
      based biological dressings to wounds using a topographically modified hydrogel
      dressing capable of simultaneous reducing the microbiological threat to a
      successful outcome may be a realistic clinical proposition.

PMID- 17022682
TI  - Kinetic measurements of protein conformation in a microchip.
AB  - This paper presents a microchip-based system for collecting kinetic time-based
      information on protein refolding and unfolding. Dynamic protein conformational
      change pathways were studied in microchannel flow using a microfluidic device. We
      present a protein-conserving approach for quantifying refolding by dynamically
      varying the concentration of the chemical denaturants, guanidine hydrochloride
      and urea. Short diffusion distances in the microchannel result in rapid
      equilibrium between protein and titrating solutions. Dilutions on the chip were
      tightly regulated using pressure controls rather than syringe-based flow, as
      verified with extensive on-chip tracer dye controls. To validate this protein
      assay method, folding transition experiments were performed using two well
      characterized proteins, human serum albumin (HSA) and bovine carbonic anhydrase
      (BCA). Transition events were monitored through fluorescence intensity shifts of
      the protein dye 8-anilino-1-naphthalenesulfonic acid (ANS) during dilutions of
      protein from urea or guanidine hydrochloride solutions. The enzymatic activity of
      refolded BCA was measured by UV absorption through the conversion of p
      nitrophenyl acetate (p-NPA). The microchip protein refolding transitions using
      ANS were well-correlated with conventional plate-based experiments. The
      microfluidic platform enables refolding studies to identify rapidly the optimal
      folding strategy for a protein using small quantities of material.

PMID- 17022683
TI  - Cell detachment model for an antibody-based microfluidic cancer screening system.
AB  - We consider cells bound to the floor of a microfluidic channel and present a
      model of their flow-induced detachment. We approximate hydrodynamic force and
      cell elastic response using static finite-element simulation of a single cell.
      Detachment is assumed to occur when hydrodynamic and adhesive forces are roughly
      equal. The result is extended to multiple cells at the device level using a
      sigmoidal curve fit. The model is applied to a microfluidic cancer-screening
      device that discriminates between normal epithelial cells and cells infected with
      human papillomavirus (HPV), on the basis of increased expression of the
      transmembrane protein alpha6 integrin in the latter. Here, the cells to be tested
      are bound to a microchannel floor coated with anti alpha6 integrin antibodies. In
      an appropriate flow rate range, normal cells are washed away while HPV-infected
      cells remain bound. The model allows interpolation between data points to choose
      the optimal flow rate and provides insight into interaction of cell mechanical
      properties and the flow-induced detachment mechanism. Notably, the results
      suggest a significant influence of cell elastic response on detachment.

PMID- 17022684
TI  - Integrated sampling procedure for metabolome analysis.
AB  - Metabolome analysis, the analysis of large sets of intracellular metabolites, has
      become an important systems analysis method in biotechnological and
      pharmaceutical research. In metabolic engineering, the integration of metabolome
      data with fluxome and proteome data into large-scale mathematical models promises
      to foster rational strategies for strain and cell line improvement. However, the
      development of reproducible sampling procedures for quantitative analysis of
      intracellular metabolite concentrations represents a major challenge,
      accomplishing (i) fast transfer of sample, (ii) efficient quenching of
      metabolism, (iii) quantitative metabolite extraction, and (iv) optimum sample
      conditioning for subsequent quantitative analysis. In addressing these
      requirements, we propose an integrated sampling procedure. Simultaneous quenching
      and quantitative extraction of intracellular metabolites were realized by short
      time exposure of cells to temperatures < or =95 degrees C, where intracellular
      metabolites are released quantitatively. Based on these findings, we combined
      principles of heat transfer with knowledge on physiology, for example, turnover
      rates of energy metabolites, to develop an optimized sampling procedure based on
      a coiled single tube heat exchanger. As a result, this sampling procedure enables
      reliable and reproducible measurements through (i) the integration of three unit
      operations into a one unit operation, (ii) the avoidance of any alteration of the
      sample due to chemical reagents in quenching and extraction, and (iii)
      automation. A sampling frequency of 5 s(-)(1) and an overall individual sample
      processing time faster than 30 s allow observing responses of intracellular
      metabolite concentrations to extracellular stimuli on a subsecond time scale.
      Recovery and reliability of the unit operations were analyzed. Impact of sample
      conditioning on subsequent IC-MS analysis of metabolites was examined as well.
      The integrated sampling procedure was validated through consistent results from
      steady-state metabolite analysis of Escherichia coli cultivated in a chemostat at
      D = 0.1 h(-)(1).

PMID- 17022685
TI  - In situ monitoring of cell concentration in a photobioreactor using image
      analysis: comparison of uniform light distribution model and artificial neural
      networks.
AB  - Light intensity is a very important factor that determines the growth of
      photosynthetic cells. In this study, the light distribution in a photobioreactor
      was analyzed by processing the images captured with a digital camera. The contour
      images obtained by filtering the original images clearly showed the effects of
      the cell concentration and external light intensity on the light distribution.
      Image-processing techniques were then applied to predict the cell density in the
      photobioreactor. To correlate the cell concentration with the light intensity in
      the photobioreactor, the captured images were processed using two different
      approaches. The first method involved the use of an average gray value after
      deriving a simplified model equation that could be related to the cell density.
      The second method involved the use of local points instead of a representative
      value. In this case, an artificial neural network model was adopted to infer the
      cell density from the information of the local points. By using these two
      methods, it was possible to relate the image data to the cell concentration.
      Finally, we compared these two methods with regard to their accuracy, easiness,
      and effectiveness.

PMID- 17022686
TI  - Regulating expression of pyruvate kinase in Bacillus subtilis for control of
      growth rate and formation of acidic byproducts.
AB  - Our prior work has shown that a pyk mutant of Bacillus subtilis exhibited
      diminished acidic byproduct accumulation, dramatically elevated
      phosphoenolpyruvate (PEP) pool, and reduced growth rate. To determine if a low
      acetate-producing but fast-growing strain of B. subtilis could be developed, we
      placed the expression of the pyk gene under the control of an inducible promoter.
      Enzyme measurements proved that PYK activity of the inducible PYK mutant (iPYK)
      increases with the isopropyl-beta-d-thiogalactopyranoside concentration. Batch
      growth experiments showed that growth rate and acid formation are closely related
      to the induction level of pyk. Measurements of cell growth rate and acetate
      formation of the iPYK mutant at different induction levels revealed that a PYK
      activity of about 12% of wild-type allows for good growth rate (0.4 h(-)(1)
      versus 0.63 h(-)(1) of wild-type) and low acetate production (0.26 g/L versus
      1.05 g/L of wild-type). This is the first report to our knowledge of a
      metabolically engineered B. subtilis strain that allows good growth rate and low
      acid production in batch cultures. Finally, it was found that, by varying the pyk
      induction level, intracellular PEP concentration can be controlled over a wide
      range. The intracellular PEP concentration is intimately connected to the
      regulation of the transport of phosphotransferase system (PTS) sugars in the
      presence of glucose. Because there is no other method for modulating
      intracellular PEP levels, this finding represents a major advance in one's
      ability to dissect the function of the PTS and sugar metabolism in bacteria.

PMID- 17022687
TI  - On-line measurement of gas production rates.
AB  - Gas evolution rates represent an important variable to track in biological and
      certain electrochemical processes. Accurate gas flow rate sensors exist for gas
      streams possessing a pressure head, such as when pressurized air or oxygen is
      delivered to a fermentation process. However, these devices impose pressure heads
      that can inhibit gas production and, therefore, yield false measurements.
      Examples of effected processes would include electrochemical production of a gas
      at the electrode (e.g., electrolysis) or anaerobic fermentation (e.g., anaerobic
      production of methane). In this work, we present an on-line gas measurement
      technique that measures on-line gas production from an anaerobic microbial
      process that is continuously fed simulated food waste over a 6-month period.
      Commentary is given on the sensor's accuracy and ease of use within the context
      of long-term operation, ability to measure both low and high gas production
      rates, as well as its potential for process control and system-health monitoring.

PMID- 17022688
TI  - Rapid and direct quantitative RT-PCR method to measure promoter activity.
AB  - This Note describes a novel rapid and direct quantitative method for examining
      the activity of genetic response elements. This method will provide an
      alternative to the classically used "reporter gene" activity assays. We show that
      a transfected genetic cis-regulatory element that responds to the transcription
      factor p53 gives a quantitative read-out at the RNA level that parallels that of
      an endogenous p53 responsive gene, p21 waf1/cip1. The correlation between the
      endogenous p21 gene expression in response to p53 and the transfected cis element
      is remarkable. This method is more direct and potentially faster than traditional
      promoter-reporter assays.

PMID- 17022690
TI  - Whole genome expression analysis for biologic rational pathway modeling:
      application in cancer prognosis and therapy prediction.
AB  - Using semi-quantitative microarray technology, almost every one of the
      approximately 30 000 human genes can be analyzed simultaneously with a low rate
      of false-positives, a high specificity, and a high quantification accuracy. This
      is supported by data from comparative studies of microarrays and reverse
      transcription PCR for established cancer genes including those for epidermal
      growth factor receptor (EGFR), human epidermal growth factor receptor-2
      (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase
      type plasminogen activator (PLAU), and plasminogen activator inhibitor-1
      (SERPINE1). As such, semi-quantitative expression data provide an almost
      completely comprehensive background of biological knowledge that can be applied
      to cancer diagnostics. In clinical terms, expression profiling may be able to
      provide significant information regarding (i) the identification of high-risk
      patients requiring aggressive chemotherapy; (ii) the pathway control of therapy
      predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for
      biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv)
      additional support for decisions about switching therapy; (v) target discovery;
      and (vi) the prediction of the course of new therapies in clinical trials. In
      conclusion, whole genome expression analysis might be able to determine important
      genes related to cancer progression and adjuvant chemotherapy resistance,
      especially in the context of new approaches involving primary systemic
      chemotherapy. In this review, we will survey the current progress in whole genome
      expression analyses for cancer prognosis and prediction. Special emphasis is
      given to the approach of combining biostatistical analysis of expression data
      with knowledge of biochemical and genetic pathways.

PMID- 17022691
TI  - Plasma and cerebrospinal fluid-based protein biomarkers for motor neuron disease.
AB  - Motor neuron diseases (MNDs) and, in particular, amyotrophic lateral sclerosis
      (ALS), are a heterogeneous group of neurologic disorders characterized by the
      progressive loss of motor function. In ALS, a selective and relentless
      degeneration of both upper and lower motor neurons occurs, culminating in
      mortality typically within 5 years of symptom onset. However, survival rates vary
      among individual patients and can be from a few months to >10 years from
      diagnosis. Inadequacies in disease detection and treatment, along with a lack of
      diagnostic and prognostic tools, have prompted many to turn to proteomics-based
      biomarker discovery efforts. Proteomics refers to the study of the proteins
      expressed by a genome at a particular time, and the proteome can respond to and
      reflect the status of an organism, including health and disease states. Although
      an emerging field, proteomic applications promise to uncover biomarkers critical
      for differentiating patients with ALS and other MNDs from healthy individuals and
      from patients affected by other diseases. Ideally, these studies will also
      provide mechanistic information to facilitate identification of new drug targets
      for subsequent therapeutic development. In addition to proper experimental
      design, standard operating procedures for sample acquisition, preprocessing, and
      storage must be developed. Biological samples typically analyzed in proteomic
      studies of neurologic diseases include both plasma and cerebrospinal fluid (CSF).
      Recent studies have identified individual proteins and/or protein panels from
      blood plasma and CSF that represent putative biomarkers for ALS, although many of
      these proteins are not unique to this disease. Continued investigations are
      required to validate these initial findings and to further pursue the role of
      these proteins as diagnostic biomarkers or surrogate markers of disease
      progression. Protein biomarkers specific to ALS will additionally function to
      evaluate drug efficacy in clinical trials and to identify novel targets for drug
      design. It is hoped that proteomic technologies will soon integrate the basic
      biology of ALS with mechanistic disease information to achieve success in the
      clinical setting.

PMID- 17022693
TI  - Determination of complement factor H functional polymorphisms (V62I, Y402H, and
      E936D) using sequence-specific primer PCR and restriction fragment length
      polymorphisms.
AB  - BACKGROUND: Complement factor H (CFH; HF) is an essential regulatory protein that
      plays a critical role in the homeostasis of the complement system in plasma.
      Several polymorphisms and mutations in the complement factor H gene (CFH; HF1)
      have been identified. These have revealed interesting associations with hemolytic
      uremic syndrome and age-related macular degeneration. METHODS AND RESULTS: The
      aim of this study was to develop a rapid and reliable assay for determining
      genotypic variants of the CFH gene. Sequence-specific primer PCR and restriction
      fragment length polymorphism techniques were chosen for the analysis of CFH
      polymorphisms. The assays detected the following published single nucleotide
      polymorphisms of CFH in our Caucasian population (n = 271): rs800292, 257G-->A
      (V62I); rs1061170, 1277T-->C (Y402H); and rs1065489, 2881G-->T (E936D). The
      allele frequencies (257G = 0.850, 1277T = 0.574, and 2881G = 0.839) that we
      obtained from a healthy Hungarian population were consistent with previously
      published results. CONCLUSION: These analytical methods are simple, reliable, and
      rapid to perform, and are amenable to automation. Therefore, they could
      facilitate large-scale genotypic analyses of the CFH gene in various diseases,
      such as hemolytic-uremic syndrome, age-related macular degeneration, and
      cardiovascular diseases.

PMID- 17022694
TI  - Detection of acquired Janus kinase 2 V617F mutation in myeloproliferative
      disorders by fluorescence melting curve analysis.
AB  - BACKGROUND: The genetic lesion underlying the pathogenesis of chronic
      myeloproliferative disorders (MPDs) has been identified in the Janus kinase 2
      (JAK2) gene. A point mutation in codon 617 causes a valine to phenylalanine
      substitution (V617F) in the JH2 autoinhibitory region of the protein, resulting
      in constitutive activation of the tyrosine kinase. The high prevalence of this
      conserved mutation in MPD makes it an excellent candidate as a diagnostic
      molecular marker. METHODS AND RESULTS: We report here the development and
      validation of a single oligonucleotide probe-based PCR approach using
      fluorescence melting curve analysis for point mutation detection in DNA derived
      from unfractionated peripheral blood samples. Using this assay and serial
      dilutions of an erythroleukemia cell line harboring the homozygous JAK2 V617F
      mutation, we successfully detected the mutation within a background of wild type
      sequences at a sensitivity of 2.5%. Our novel fluorescence probe-based assay was
      compared with allele-specific PCR-gel assay and sequencing techniques. Using the
      single probe assay, we examined 70 cases with a presumptive diagnosis of MPD, of
      which 38 (54%) yielded positive results for the presence of the JAK2 V617F
      mutation, and 92 follicular lymphoma cases, which were negative for the JAK2
      V617F mutation. Additionally, the probe-based assay detected a previously
      unreported T>C base substitution at nucleotide 2342 (JAK2, codon 616), which was
      not detected by an allele-specific PCR assay. CONCLUSION: The single fluorescent
      probe-based assay described here is a rapid, homogeneous, and robust method for
      the detection of the JAK2 V617F mutation with favorable performance
      characteristics that make it advantageous for clinical diagnosis.

PMID- 17022692
TI  - Targeted therapy for cystic fibrosis: cystic fibrosis transmembrane conductance
      regulator mutation-specific pharmacologic strategies.
AB  - Cystic fibrosis (CF) results from the absence or dysfunction of a single protein,
      the CF transmembrane conductance regulator (CFTR). CFTR plays a critical role in
      the regulation of ion transport in a number of exocrine epithelia. Improvement or
      restoration of CFTR function, where it is deficient, should improve the CF
      phenotype. There are >1000 reported disease-causing mutations of the CFTR gene.
      Recent investigations have afforded a better understanding of the mechanism of
      dysfunction of many of these mutant CFTRs, and have allowed them to be classified
      according to their mechanism of dysfunction. These data, as well as an enhanced
      understanding of the role of CFTR in regulating epithelial ion transport, have
      led to the development of therapeutic strategies based on pharmacologic
      enhancement or repair of mutant CFTR dysfunction. The strategy, termed 'protein
      repair therapy', is aimed at improving the regulation of epithelial ion transport
      by mutant CFTRs in a mutation-specific fashion. The grouping of CFTR gene
      mutations, according to mechanism of dysfunction, yields some guidance as to
      which pharmacologic repair agents may be useful for specific CFTR mutations.
      Recent data has suggested that combinations of pharmacologic repair agents may be
      necessary to obtain clinically meaningful CFTR repair. Nevertheless, such
      strategies to improve mutant CFTR function hold great promise for the development
      of novel therapies aimed at correcting the underlying pathophysiology of CF.

PMID- 17022695
TI  - Broad-range bacterial and fungal DNA amplification on vitreous humor from
      suspected endophthalmitis patients.
AB  - BACKGROUND: Prompt and accurate diagnosis of infectious endophthalmitis is
      crucial for rapid and effective treatment. By identifying whether the causative
      pathogen is bacterial or fungal, a rational approach for the use of
      antibacterials or corticosteroids, respectively, can be followed. AIM: To assess
      the clinical utility of broad-range bacterial and fungal DNA amplification in the
      detection of endophthalmitis (postoperative, posttraumatic, and endogenous).
      METHODS: In a prospective study, vitreous humor samples from 70 patients with the
      clinical diagnosis of presumed endophthalmitis, and from 30 patients undergoing
      surgery for non-infectious causes, were subjected to routine microbiologic and
      molecular investigation. DNA extracted from a 50 microL sample was amplified by
      primers targeting the conserved 16S and 18S ribosomal RNA gene sequences of
      bacteria and fungi, respectively. Reagents for bacterial DNA amplification were
      decontaminated of endogenous DNA using 8-methoxypsoralen and long wave UV
      treatment. RESULTS AND DISCUSSION: A total of 35 specimens were positive for
      bacteria or fungi by culture. Of these, Gram-positive organisms were isolated in
      19 specimens, Gram-negative organisms in 13 specimens and fungi in 3 specimens.
      Pseudomonas species, coagulase-negative Staphylococcus, and Streptococcus species
      were the main etiological agents isolated. Bacterial DNA amplification resulted
      in 49 positive specimens, compared with 32 positive specimens by culture; and
      fungal DNA amplification resulted in 11 positive specimens, compared with 3
      positive specimens by culture. All control specimens were negative for both
      culture and DNA amplification. CONCLUSION: DNA extracted using a single
      extraction protocol from 50 microL of vitreous humor and amplified with broad
      range bacterial and fungal primers will enable the rapid differentiation (within
      14 hours) between bacterial and fungal endophthalmitis and allow tailoring of
      therapy to individual patients.

PMID- 17022696
TI  - Enhanced detection of microsatellite instability and mismatch repair gene
      expression in cutaneous squamous cell carcinomas.
AB  - BACKGROUND: Microsatellite instability (MSI) is a phenotypic characteristic of
      tumors with biallelic inactivation of mismatch repair genes, such as MSH2 or
      MLH1, and contributes to malignant transformation. AIMS: The aim of this study
      was to examine the prevalence of MSI in cutaneous squamous cell carcinoma (SCC)
      using a PCR and fluorescent-based detection system. These methods of analysis
      offer several advantages over the use of silver staining and autoradiographic
      techniques. We also aimed to determine if MSI status correlated with expression
      of the MSH2 and MLH1 mismatch repair proteins in these cutaneous SCC samples.
      METHODS: The MSI status of 22 histologically confirmed invasive cutaneous SCC
      samples were analyzed at five microsatellite markers (the National Cancer
      Institute's Bethesda panel of two mononucleotide and three dinucleotide markers)
      using a PCR and fluorescent-based detection system. Immunohistochemical analysis
      of MSH2 and MLH1 protein expression was also carried out on the SCC samples.
      RESULTS: Only one case of cutaneous SCC displayed MSI. This was found at just one
      of five markers, and thus was low frequency MSI. All 22 cutaneous SCC cases
      strongly expressed MSH2 protein. Eighteen (82%) of the cutaneous SCC cases showed
      moderate to strong expression of MLH1 protein. The remaining four cases of
      cutaneous SCC were negative for MLH1 protein. Therefore, the majority of the SCC
      patients analyzed showed a correlation between absence of MSI and expression of
      MSH2 and MLH1 proteins. CONCLUSIONS: MSI is uncommon in cutaneous SCC. In
      addition, MSH2 was strongly expressed in all SCC samples analyzed and appeared to
      be upregulated when compared with the corresponding normal tissue. MLH1 protein
      was not detected in 4 of 22 SCC cases, although it was expressed in the
      corresponding normal tissue, suggesting that inactivation of MLH1 may be a late
      event in a subset of invasive SCC cases.

PMID- 17022697
TI  - Laparoscopic management of gastric cancer.

PMID- 17022699
TI  - Effect of Helicobacter pylori eradication therapy in rosacea patients.
AB  - OBJECTIVE: The causal relation between rosacea and Helicobacter pylori infection
      is discussed. We evaluated the clinical evolution of rosacea after infection
      eradication. PATIENTS AND METHODS: We have prospectively studied 44 patients
      diagnosed with rosacea. Helicobacter pylori infection was determined, and
      infected patients were treated with eradication therapy. The evolution of
      dermatological symptoms in a subgroup of 29 infected patients in whom eradication
      had been achieved was followed during 16.8 (+/- 17.8) months. Median age was 50.6
      (+/- 14.1) years for 22 women (75.9%) and 7 men (24.1%). Clinical response
      according to gender and clinical subtype of rosacea was evaluated. RESULTS:
      Complete improvement was observed in 10 patients (34.5%; 95% CI: 18.6-54.3%),
      relevant improvement in 9 (31.1%; 95% CI: 16-51%), poor improvement in 5 (17.2%;
      95% CI: 6.5-36.4%), and absence of improvement in 5 cases (17.2%; 95% CI: 6.5
      36.4%). No significant differences in dermatological evolution according to sex
      were observed. Regarding subtype of rosacea there was a relevant improvement in
      83.3% (95% CI: 64.1-93.8%) of cases with papulopustular type as opposed to 36.5%
      (95% CI: 20-56.1%) of cases with erythematous predominance, p = 0.02.
      CONCLUSIONS: Based on these results, the relation between Helicobacter pylori and
      rosacea is supported, and infection should be investigated in these patients
      because an appreciable percentage of patients diagnosed with rosacea and
      Helicobacter pylori infection can benefit from eradication therapy, mainly in the
      papulopustular subtype.

PMID- 17022698
TI  - Laparoscopic gastrectomy for gastric adenocarcinoma. Long-term results.
AB  - BACKGROUND: The objective of our paper is to report on the long-term results of
      patients with gastric cancer treated by mini-invasive surgery with "intention-to
      treat" laparoscopy. PATIENTS AND METHODS: Between June 1993 and January 2006, 130
      patients comprising 94 men and 36 women with gastric adenocarcinoma were
      prospectively selected by two surgical teams in three hospitals based on a prior
      agreement (CHU Charleroi, Belgium, Centre Hospitalier de Luxembourg and Zumarraga
      Hospital, Spain). Patients with adenocarcinoma of the cardia were excluded. Mean
      age of patients was 68 years (range, 37-85 years). RESULTS: Post-operative
      mortality within 60 days of operation was 6 patients; 109 patients were therefore
      properly followed up for an average of 49 months (range, 2-153 months).Average
      survival time for 10 non-resected patients was 4.5 months. Average survival rate
      for all 14 palliatively resected patients was 6.9 months. Actuarial 5-year
      survival rate for R0-type surgery was 35%. Global actuarial 5-year survival rate
      after resective surgery was 31%. CONCLUSIONS: Laparoscopic gastrectomy with any
      kind of lymphadenectomy is a major but safe operation with acceptable mortality
      and morbility rates in patients with advanced gastric cancer, usually in poor
      general condition. Laparoscopic gastrectomy for locally advanced cancers is
      equivalent to laparotomy as far as long-term oncological results are concerned.

PMID- 17022700
TI  - Extraintestinal manifestations of Crohn's disease: prevalence and related
      factors.
AB  - BACKGROUND: Patients with inflammatory bowel disease may suffer one or more
      extraintestinal manifestations during the course of their condition, these being
      more frequent in Crohn s disease. The aim of our study was to evaluate the
      prevalence of extraintestinal manifestations in patients with Crohn s disease in
      our healthcare area, and to assess the relationship between its presence and
      diverse clinical-evolutionary variables. MATERIAL AND METHODS: Extraintestinal
      manifestations in 157 patients diagnosed with Crohn s disease in our center were
      retrospectively studied. The clinical-evolutionary characteristics of this
      population were compared with respect to the presence or absence of different
      extraintestinal manifestations. RESULTS: Seventy-two patients (46%) presented at
      least with one extraintestinal manifestation. Thirty-one percent were colitis
      related manifestations (22% rheumatologic, 13% muco-cutaneous, 4%
      ophthalmologic), 11% cholelithiasis, 8% nephrolithiasis, 3% thromboembolic
      illness, and other manifestations were less frequent. Fourteen percent presented
      with more than one extraintestinal manifestation. Rheumatologic and muco
      cutaneous manifestations were significantly more frequent in patients with
      disease confined to the colon. Cholelithiasis was significantly associated to
      those over 40 and also to males. Nephrolithiasis was also significantly
      associated to those over 40, and thromboembolic illness was linked to females.
      CONCLUSIONS: forty-six percent of patients with Crohn s disease presented at
      least with one extraintestinal manifestation. Thirty-one percent presented with
      colitis-related manifestations, rheumatologic and muco-cutaneous manifestations
      being the most frequent, whereas hepatic manifestations were infrequent.
      Rheumatologic and muco-cutaneous manifestations were more frequent in patients
      with disease confined to the colon.

PMID- 17022701
TI  - Impact of gastroesophageal reflux symptoms on health resource usage and work
      absenteeism in Spain.
AB  - OBJECTIVES: To estimate the impact of gastroesophageal reflux (GER) symptoms on
      the utilization of healthcare services and work absenteeism in Spain. METHODS: A
      cross-sectional study on 2,500 subjects representative of the Spanish population
      from 40 to 79 years of age. Data were collected via a telephone interview in
      January 2002 using Locke s questionnaire after its cross-cultural adaptation and
      validation for telephone use in Spain. RESULTS: GER is responsible for 296.8
      doctor consultations (95% CI: 245.3-348.7) per 1,000 inhabitants per year, for 24
      esophagogastrointestinal radiographic studies per 1,000 inhabitants per year (95%
      CI: 18-30), for 32.4 (95% CI: 25.5-39.3) high digestive endoscopies per 1,000
      inhabitants per year, and for the loss of 201 (95% CI: 0-411.1) working days per
      1,000 employed inhabitants with GER per year. In relation to medication intake,
      GER resulted in 4,092 (95% CI: 3,300-5,133) treatment days with H2 antagonists
      per 1,000 inhabitants per year, 9,030 (95% CI: 7,846-10,332) treatment days with
      proton pump inhibitors per 1,000 inhabitants per year, and 1,082 (95% CI: 519
      1,549) treatment days with prokinetics per 1,000 inhabitants per year.
      CONCLUSIONS: GER has a large impact on the utilization of healthcare resources
      and work absenteeism in Spain, in contrast to the widespread belief that it is an
      illness of little importance.

PMID- 17022702
TI  - Gastric angiogenesis and Helicobacter pylori infection.
AB  - The formation of new blood vessels seen in conditions commonly associated with
      Helicobacter pylori (H. pylori) infection, including gastritis, peptic ulcer, and
      gastric carcinoma, prompts consideration of a potential relationship between
      mucosal colonization by this organism and the angiogenic process. H. pylori
      directly or indirectly damages endothelial cells, which induces a number of
      changes in the microvasculature of the gastric mucosa. In H. pylori-associated
      conditions, that is, in gastritis, peptic ulcer and gastric carcinoma, there is
      an increased concentration of angiogenic factors, and subsequently a formation of
      new blood vessels. However, this early angiogenesis -which is activated to repair
      the gastric mucosa- is subsequently inhibited in patients with peptic ulcer, and
      ulcer healing is thus delayed. This may be due to the antiproliferative action of
      this organism on endothelial cells. While the angiogenic process becomes
      inhibited in infected patients with peptic ulcer, it remains seemingly active in
      those with gastritis or gastric cancer. This fact is in support of the notion
      suggested by various studies that peptic ulcer and gastric cancer are mutually
      excluding conditions. In the case of gastric cancer, neoangiogenesis would
      enhance nutrient and oxygen supply to cancer cells, and thus tumor growth and
      metastatic spread.

PMID- 17022703
TI  - Is the string test a useful alternative to gastroscopy with biopsy for H. pylori
      identification?

PMID- 17022704
TI  - Massive hepatic amyloidosis with fatal hepatic failure.

PMID- 17022705
TI  - [Acute pancreatitis and protein C deficiency as a cause of mesenteric venous
      thrombosis].

PMID- 17022706
TI  - [Blue rubber bled nevus syndrome diagnosed bu capsule endoscopy].

PMID- 17022707
TI  - [Spontaneous pneumococcal peritonitis in a cirrhotic patient without respiratory
      focus].

PMID- 17022708
TI  - [Biliary actinomycosis. A case report].

PMID- 17022709
TI  - [Unusual complication of spider angiomas: hemorrhagic diathesis controlled with
      antihormonal therapy (tamoxifen)].

PMID- 17022710
TI  - [Acute fulminant colitis caused by intestinal amebiasis].

PMID- 17022711
TI  - [Getting ready for a potential avian influenza pandemics. The contribution of
      hospital pharmacy].

PMID- 17022712
TI  - [Avian influenza pandemics: reality or fiction?].

PMID- 17022713
TI  - [The European Union in favor of children].

PMID- 17022714
TI  - [Pharmacoeconomic assessment of taxanes as first-line therapy for advanced or
      metastatic non-microcytic lung cancer].
AB  - OBJECTIVE: The goal of this study was to determine the effectiveness of taxane
      containing regimens versus non-taxane-containing regimens using a metanalysis and
      its subsequent pharmacoeconomic assessment to define the role of taxanes as first
      line therapy for non micro-cytic lung cancer. METHOD: A search of the MEDLINE
      database from 2000 to June 2005 was performed. The search was restricted to phase
      III clinical trials, and 29 papers were selected. Effectivity measures considered
      included: objective response, 1- and 2-year survival. Maentel-Haenszel combined
      odds ratio (OR) was estimated in the metanalysis. The statistical analysis of
      effectiveness across categories was performed using a one-way analysis of
      variance (ANOVA). Differences were statistically considered for p values = 0.01.
      All results obtained were weighted according to number of patients. RESULTS: OR
      estimates for the various effectiveness variables showed statistically
      significant differences when 2-year survival was considered both for taxanes in
      general and docetaxel specifically versus non-taxane regimens. These same results
      are seen when the effectiveness analysis is performed using ANOVA. For the
      pharmacoeconomic analysis taxane-free regimens were considered as reference, this
      being of choice for comparisons versus paclitaxel-containing regimens whereas the
      selection of docetaxel-containing schemes represents additional costs per extra
      effectiveness unit that oscillate between 26,559 and 96,527 (2-year survival and
      objective response, respectively) versus taxane-free regimens. The sensitivity
      analysis ultimately confirmed our study s results. CONCLUSIONS: To conclude,
      taxane-containing schemes are valid therapeutic options, but at a very high cost.

PMID- 17022715
TI  - [Effectiveness and safety of adalimumab and etanercept for rheumatoid arthritis
      in a third-level hospital].
AB  - OBJECTIVE: To assess the effectiveness of adalimumab and etanercept at 6 and 12
      months after therapy onset using DAS28, EULAR (European League Against
      Rheumatism), and ACR (American College of Rheumatology) criteria, and to analyze
      safety. METHOD: A prospective, 12-month, observational study of a patient cohort
      diagnosed with rheumatoid arthritis who were started on adalimumab or etanercept
      at the Rheumatology Department between January 2003 and December 2004. DAS28,
      EULAR, and ACR criteria were examined at 6 and 12 months. An intention-to-treat
      analysis was performed, and adverse reactions were quantitized. RESULTS: Ninety
      nine patients were included - 50 on adalimumab and 49 on etanercept. Of these, 30
      and 20%, respectively, received monotherapy. No differences in effectiveness were
      seen between both drugs during the studied periods of time according to DAS28.
      EULAR response to adalimumab at 6 and 12 months was: good 28 and 38%; moderate 40
      and 36%; nil 10 and 4%; regarding etanercept at 6 and 12 months: good 29 and 43%;
      moderate 31 and 24%; nil 18 and 10%. As regards adalimumab at 6 and 12 months:
      ACR20: 64 and 62%; ACR50: 44 and 46%; ACR70: 22 and 26%; as regards etanercept at
      6 and 12 months: ACR20: 61 and 65%; ACR50: 41 and 45%; ACR70: 16 and 24%. Eleven
      patients discontinued therapy in each group. CONCLUSIONS: Adalimumab and
      etanercept had a similar effectiveness in our population. Criteria of use may
      condition results, and thus awareness of other hospitals experience is
      encouraged.

PMID- 17022716
TI  - [Effectiveness and safety of imatinib in seven gastrointestinal stromal tumor
      cases].
AB  - OBJECTIVE: To measure the effectiveness and safety of imatinib for
      gstrointestinal stromal tumors (GISTs). METHOD: A retrospective study from 1993
      through June 2005 by identifying all patients diagnosed with GIST by the
      Pathology Department. The medical records of those treated with imatinib were
      reviewed. Demographic, diagnostic, therapeutic, and outcome-related data were
      collected. RESULTS: Twenty-five patients were identified, 7 of them treated with
      imatinib. Total responses were 4/7; 2/7 cases were complete responses, and 2/7
      were partial responses. Mean actuarial disease-free survival was 10 months, and
      overall survival was 44 months. Adverse reactions (ARs) reported included: 33%
      (5) gastrointestinal events, 40% (6) dermatologic events and/or edema, 14% (2)
      blood toxicity, and 13% (2) asthenia. In all, 2/7 patients experienced no
      imatinib-related toxicity. CONCLUSIONS: In our experience, imatinib is an
      effective, well tolerated therapy for malignant [c-Kit (CD117)-positive], non
      resectable and/or metastatic GIST.

PMID- 17022717
TI  - [Medication errors in two Brazilian hospitals].
AB  - OBJECTIVE: To determine medication errors in a public and in a private hospital.
      METHOD: Cross-sectional. 638 dosis opportunities for errors (administered dosis +
      omitted dosis) were assessed in January, 2005. Medication error was defined as
      any given dose different from a legible prescription on patient chart. The error
      rate was calculated by the following equation: number of dosis/error
      opportunities. The errors were classified according to the categories: omission,
      unordered dose, extra-dose, wrong dose, wrong route, wrong form, wrong time.
      RESULTS: Out of 638 opportunities of error, 209 (32,9%) were wrong in some way.
      When wrong time errors were excluded, this rate decreased to 156 (25%). The most
      frequent types of errors were omission and unordered dosis, 67 (10,5%) and 65
      (10,2%), respectively. There was no significant difference on the total error
      rate according to the type of hospital (public or private). CONCLUSIONS: The
      public hospital showed a double-fold unordered dose error rate as compared to the
      private hospital. Inversely, the private hospital showed a double-fold wrong time
      error rate than the public hospital.

PMID- 17022718
TI  - [Clinical pharmacogenomics for CYP2C8 and CYP2C9: general concepts and
      application to the use of NSAIDs].
AB  - OBJECTIVE: To study the major mutations in genes CYP2C8 and CYP2C9, their
      frequency in populations of diverse ethnical descent, their analysis methods, and
      the major drugs with affected metabolism, with a special emphasis on NSAIDs.
      METHOD: Repeated searches of Pubmed (January 1966-January 2006) and Scholar
      Google were performed. All searches were restricted to studies in humans, and
      papers not written in Spanish or English were excluded. RESULTS: Ten allelic
      variants of CYP2C8 and 24 of CYP2C have been reported. Not all of them exert a
      relevant effect on drug metabolism. In Caucasians 22% of CYP2C8 genes and 31% of
      CYP2C9 genes have mutations. In Asians fewer than 1% and nearly 3% are mutated,
      respectively. Major identification methods include endonuclease digestion, PCR,
      pyrosequencing, and microarrays. Not all NSAIDs are exclusive substrates for
      CYP2C8/9. The usefulness of allelic variant analysis varies with each individual
      drug. The risk for digestive hemorrhage associated with the CYP2C9 genotype is
      particularly relevant when using aceclofenac, celecoxib, diclofenac, ibuprofen,
      indomethacin, lornoxicam, piroxicam, or naproxen. CONCLUSIONS: Although CYP2C8/9
      activity plays an essential role in the metabolism of and clinical response to
      many NSAIDs, the use of pharmacogenomic techniques is not equally useful for all
      these drugs.

PMID- 17022719
TI  - [Pharmacovigilance in a paediatric intensive care unit].
AB  - OBJECTIVE: To analyze suspected drug-related adverse events as reported by
      pharmacists in a pediatric intensive care unit. METHOD: Suspected drug-related
      adverse events were recorded as reported by pharmacists in an intensive care unit
      during hospital rounds (these were neither systematic nor continued) or patient
      visits to our clinic (April 2004-May 2005). Later on, the pharmacovigilance
      subcommittee prospectively analyzed such suspected events in order to confirm
      them and classify them according to their rules. RESULTS: Nineteen suspected
      adverse events were reported for 17 patients; 15 were confirmed (78%). In six
      cases the pharmacist suggested the way the adverse event was eventually treated.
      Three cases required admission to an ICU. Drug classes most commonly involved
      included antimicrobials, anti-epileptic drugs, and immunosuppressants. Severity
      was: fatal 20%, serious 34%, moderate 13%, mild 33%. Causality was definitely
      established for 13%, probable for 54%, and possible for 33% of patients; 20% of
      events were considered avoidable. CONCLUSIONS: Adverse events reported by
      pharmacists were few, as they could not attend hospital rounds on a regular
      basis. Imputability was difficult due to critical patient conditions. Most
      suspected events were later confirmed. Treatment involved therapy adjustments
      according to individual patient characteristics.

PMID- 17022720
TI  - [Desensitization to cotrimoxazole, rifampicin and penicillin G in nine patients
      with prior hypersensitivity].
AB  - OBJECTIVE: To present a protocol for the administration and development technique
      of the desensitization regimens for cotrimoxazole, rifampicin and penicillin G
      hypersensibility. METHOD: A review of the available desensitization protocols for
      these antibiotics and a retrospective study of desensitization processes
      undertaken in the center from 1998. A development technique of the antibiotic
      dosages was designed. RESULTS: Desensitization regimens for cotrimoxazole,
      rifampicin and penicillin G undertaken in the center in 9 patients came from a
      protocol by Glucksteins et al., Holland et al. and Wendal et al., respectively.
      After the literature review and the satisfactory results that allowed subsequent
      antibiotic administration in the 9 cases, these regimens were established as
      protocols of the center. CONCLUSIONS: Dosage development and patient
      administration have a practical application and can help to decrease the
      potential mistakes related to the complexity of the process.

PMID- 17022721
TI  - [Subacute cardiomyopathy and liposomal amphotericin B].

PMID- 17022722
TI  - [Neuroleptic malignant syndrome in association with tricyclic antidepressants].

PMID- 17022723
TI  - [Ocular toxicity by the use of ethambutol].

PMID- 17022724
TI  - Results of an Aboriginal community-based renal disease management program
      incorporating point of care testing for urine albumin:creatinine ratio.
AB  - INTRODUCTION: There has been a significant increase in the burden of renal
      disease among Aboriginal Australians over the past 15 years. Urine
      albumin:creatinine ratio (ACR) is a well-established marker of microalbuminuria
      and can be conveniently performed on the DCA 2000 point-of-care testing (POCT)
      analyser (Bayer Australia; Melbourne, VIC, Australia) with an on-site result
      available in 7 min. The application of the urine ACR POCT for renal disease risk
      assessment was pioneered by our group in the Umoona Kidney Project. This article
      describes the results of the management arm of the Umoona Kidney Project, which
      used point-of-care urine ACR testing for the first time within a management
      framework to monitor albuminuria in patients at highest risk of renal disease.
      The article also examines the analytical quality of POCT results and overall
      community acceptance of the Umoona Kidney Project. METHODS: Adults clinically
      assessed by Flinders Medical Centre renal specialists as being at greatest risk
      for renal disease were offered the ACE inhibitor (ACEI) perindopril on a
      voluntary basis. Selected renal markers, including POCT urine ACR (conducted on
      site by Umoona's Aboriginal health worker team), plasma electrolytes, urea,
      creatinine, calculated glomerular filtration rate and blood pressure were
      measured six monthly. Regular quality control testing was undertaken to monitor
      the analytical performance of the POCT analyser. A culturally appropriate
      questionnaire was designed and implemented to assess community satisfaction with
      the project. RESULTS: In all, 231 patient management consultations were conducted
      over a two year period, with over 70% of patients having four or more (up to a
      maximum of eight) consultations; 35 patients (mean age 49.2 [+/-2.3] years, 54%
      males) participated voluntarily in the management arm. All were overtly
      hypertensive, hypertensive with other risk factors or had diabetes. The renal
      status of these patients was followed for a mean of 63 +/- 4.5 weeks. In total,
      111 POCT urine ACR tests were performed for patient management (mean 3.2 tests
      per patient). There was no significant difference in POCT urine ACR in the study
      period with a median (and inter-quartile range) of 5.7 mg/mmol (1.2-15.2) pre
      ACEI and 4.3 mg/mmol (1.3-16.7) post-ACEI treatment (p = 0.50, Wilcoxon signed
      ranks test). The calculated glomerular filtration rate altered from 110 to 118
      mL/min (p = 0.019, paired t-test). There was no change in the group plasma
      potassium, urea and creatinine. Collectively these results indicate a
      stabilisation in renal function among the management group. Blood pressure (both
      lying and standing) fell significantly in the study period. The imprecision for
      urine ACR quality control POCT conducted during the management program was within
      nationally and internationally accepted precision goals for urine albumin,
      creatinine and ACR. Fifty community members completed the satisfaction
      questionnaire. Three-quarters of respondents felt there were no cultural barriers
      in providing a urine sample for urine ACR POCT. CONCLUSIONS: The management arm
      of the Umoona Kidney Project was effective in stabilising the renal function and
      improving the blood pressure of community members identified to be at greatest
      risk of kidney disease. POCT urine ACR testing can be utilised, not only for
      community risk assessment, but also for patient management. The Umoona Kidney
      Project was well accepted by the health service and community members.

PMID- 17022732
TI  - NK cell function in HIV-1 infection.
AB  - NK cells are critical effector cells of the innate immune response to malignancy
      and infection. These cells have a wide array of direct antiviral activities and
      have been critically implicated in the regulation and induction of an effective
      adaptive immune response. Although the pivotal role of this cell subset in the
      context of a number of viral infections is well established, the role of NK cells
      in HIV-1 infection is less well understood. Recent data has demonstrated the
      association between an NK cell receptor, KIR3DS1, and it's ligand, HLA-Bw4 with
      an isoleucine at position 80, and slower disease progression. This data suggests
      that NK cells may play an essential role in the control of HIV-1 disease, and has
      provided the impetus to begin to better understand the role of this cell subset
      in the context of HIV-1 infection, replication, and pathogenesis. Here we present
      a review of the literature pertaining to both the effect of HIV-1 infection on NK
      cell activity and the potential role that this subset of cells may play in
      controlling HIV-1 disease.

PMID- 17022733
TI  - Immunological tolerance using synthetic peptides--basic mechanisms and clinical
      application.
AB  - Dysregulation of T lymphocyte function underpins the development of autoimmune
      and allergic diseases. These autoantigen-, or allergen-reactive pathogenic T
      cells are rare within the entire immune repertoire and it is therefore desirable
      to develop more specific therapies than are currently in use to directly target
      these cells and avoid adverse side effects. The obvious approach is to use the
      antigens that are recognized to impose a state of T cell tolerance. T cells
      recognize antigens as peptide fragments and we can therefore produce the relevant
      antigens as synthetic peptides. It has been known for many years that the
      decision of the T cell to mount a productive response (immunity) or to remain
      silent (tolerance) is controlled by the form in which the antigen is
      administered. Antigen with adjuvant leads to immunity, whereas soluble antigen
      without adjuvant leads to tolerance. This paradigm has been used successfully to
      induce tolerance with soluble peptides, preventing several animal models of
      autoimmune and allergic disease. These findings obviously have exciting potential
      for translation to human diseases. However, the basic immune mechanisms that lead
      to tolerance versus immunity are only beginning to be unravelled. The "effector"
      phase of tolerance also remains controversial with evidence for T cell death,
      anergy and the development of immunoregulatory function. This latter possibility
      of specifically generating autoantigen- or allergen-reactive regulatory T cells
      is particularly attractive. Here we review recent advances in our understanding
      of the requirements for tolerance induction and the potential for establishing
      dominant immune-regulation with peptide therapy.

PMID- 17022734
TI  - Early genetic changes involved in low-grade astrocytic tumor development.
AB  - Astrocytomas represent the most common form of glial tumors. The most malignant
      grade of these tumors, glioblastoma multiforme, may arise as a malignant
      progression from low-grade astrocytoma through anaplastic astrocytoma to
      secondary GBM, or else it may arise "de novo" as primary GBM. Both types of
      glioblastoma are usually histologically indistinguishable. However, distinct
      molecular alterations have been described between them that potentially allow
      differentiation between the two mechanisms of origin. Since malignant
      transformation is a multistep process, we summarize in this review the earliest
      genetic changes that seem to be involved in the appearance and development of low
      grade astrocytic tumors, where early detection and treatment could be possible.

PMID- 17022735
TI  - Biomedical applications and potential health risks of nanomaterials: molecular
      mechanisms.
AB  - Nanotechnologies, defined as techniques aimed to conceive, characterize and
      produce material at the nanometer scale, represent a fully expanding domain, and
      one can predict without risk that production and utilization of nanomaterials
      will increase exponentially in the coming years. Applications of nanotechnologies
      are numerous, in constant development, and their potential use in the medical
      field as diagnosis and therapeutics tools is very attractive. The size
      particularity of these nanomaterials gives them novel properties, allowing them
      to adopt new comportments because of the laws of quantum physics that exist at
      this scale. However, worries are expressed regarding the exact properties that
      make these nanomaterials attractive, and questions are raised regarding their
      potential toxicity, their long-term secondary effects or their biodegradability,
      particularly when thinking of their use in the (nano)medical field. These
      questions are justified by the knowledge of the toxic effects of atmospheric
      pollution micrometric particles on health, and the fear to get an amplification
      of these effects because of the size of the materials blamed. In this paper, we
      first expose the sensed medical applications of nanomaterials, and the
      physicochemical and molecular determinants potentially responsible for
      nanomaterials biological effects. Finally, we present a synthesis of the actual
      knowledge regarding toxicological effects of nanomaterials. It is clear that, in
      regard to the almost empty field of what is known on the subject, there's an urge
      to better understand biological effects of nanomaterials, which will allow their
      safe use, in particular in the nanomedicine field.

PMID- 17022736
TI  - Molecular pathogenesis of chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is unique among malignancies since it
      represents an accumulation of B-lymphocytes resistant to apoptosis. Several
      factors are thought to confer this unusual feature to a CLL B-cell. Misbalance
      between cytoplasmic pro-survival and pro-death molecules, such as Bcl-2, Mcl-1
      and alike, appears to be one of the key factors defining B-cell longevity.
      Autocrine pathways, such as vascular endothelial growth factor-receptor pathway,
      also contribute to survival. The role of B-cell receptor (BCR) is less
      straightforward. In the last decade it became clear that CLL does not constitute
      a uniform disease, but, based on the prevalence of mutations in the BCR heavy
      chain (IgVH), can be classified into two distinct subgroups. Several molecular
      markers correlate with IgVH mutations. Some of them, like zeta-chain associated
      protein kinase, are also involved in BCR signaling and influence cell cycle. Yet
      the primary pathogenic event leading to increased proliferation and survival in
      CLL is difficult to ascertain. Molecules involved in BCR signaling pathways and
      cytoplasmic pro-survival players probably act in concert to confer resistance to
      apoptosis. In this respect, the role of the B-CLL environment, which includes
      nurse-like cells and T-cells, cannot be underestimated. Nurse-like cells provide
      stimuli necessary for perpetuation of life in CLL. On the other hand, abnormal T
      cell function, whether it is excessive immunosuppression delivered by regulatory
      T-cells or insufficient anti-tumor immunity rendered by T-helpers, allows
      malignant CLL cells to go unnoticed by the cellular immune system.

PMID- 17022737
TI  - Cannabinoid drugs and enhancement of endocannabinoid responses: strategies for a
      wide array of disease states.
AB  - The endogenous cannabinoid system has revealed potential avenues to treat many
      disease states. Medicinal indications of cannabinoid drugs including compounds
      that result in enhanced endocannabinoid responses (EER) have expanded markedly in
      recent years. The wide range of indications covers chemotherapy complications,
      tumor growth, addiction, pain, multiple sclerosis, glaucoma, inflammation, eating
      disorders, age-related neurodegenerative disorders, as well as epileptic
      seizures, traumatic brain injury, cerebral ischemia, and other excitotoxic
      insults. Indeed, a great effort has led to the discovery of agents that
      selectively activate the cannabinoid system or that enhance the endogenous
      pathways of cannabinergic signaling. The endocannabinoid system is comprised of
      three primary components: (i) cannabinoid receptors, (ii) endocannabinoid
      transport system, and (iii) hydrolysis enzymes that break down the endogenous
      ligands. Two known endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol
      (2-AG), are lipid molecules that are greatly elevated in response to a variety of
      pathological events. This increase in endocannabinoid levels is suggested to be
      part of an on-demand compensatory response. Furthermore, activation of signaling
      pathways mediated by the endogenous cannabinoid system promotes repair and cell
      survival. Similar cell maintenance effects are elicited by EER through inhibitors
      of the endocannabinoid deactivation processes (i.e., internalization and
      hydrolysis). The therapeutic potential of the endocannabinoid system has yet to
      be fully determined, and the number of medical maladies that may be treated will
      likely continue to grow. This review will underline studies that demonstrate
      medicinal applications for agents that influence the endocannabinoid system.

PMID- 17022738
TI  - Molecular aspects of stromal-parenchymal interactions in malignant neoplasms.
AB  - Carcinomas are composed of parenchymal and stromal elements, and the malignant
      behavior is principally dictated by the cancer cells. However, the malignant
      tumors not merely grow into a preexisting interstitial tissue, but they actively
      form a new stroma and modify their composition. Thus, the tumor stroma is
      significantly different from that of the neighboring tissues. Cancer cells may
      alter their stroma by cell-to-cell contact, soluble factors or by modification of
      the extracellular matrix (ECM), they induce myofibroblast differentiation and
      govern the desmoplastic stroma reaction. On the other hand, the stromal cells
      (especially the myofibroblasts) are able to modify the phenotype, invasiveness,
      metastatic capacity of carcinomas, typically promoting the progression. Regarding
      pancreatic cancer, the pancreatic stellate cells (PSCs) seem to be the key
      elements in the cross-talk between the parenchymal cells and the desmoplastic
      stroma. The tumor stroma is also rich in tumor-associated macrophages (TAM), but
      their role in the malignant process is contradictory and may be different in
      various tumor types, but most studies suggest a negative impact on the tumor
      growth. The relationship between the parenchymal and stromal elements is highly
      complex, they mutually alter their characteristics. Because the neostroma of the
      carcinomas largely seems to promote the invasiveness of the malignant tumors,
      novel therapeutic strategies are being evaluated targeting the stromal elements,
      with some encouraging, but still fragmentary results.

PMID- 17022739
TI  - Network theory to understand microarray studies of complex diseases.
AB  - Complex diseases, such as allergy, diabetes and obesity depend on altered
      interactions between multiple genes, rather than changes in a single causal gene.
      DNA microarray studies of a complex disease often implicate hundreds of genes in
      the pathogenesis. This indicates that many different mechanisms and pathways are
      involved. How can we understand such complexity? How can hypotheses be formulated
      and tested? One approach is to organize the data in network models and to analyze
      these in a top-down manner. Globally, networks in nature are often characterized
      by a small number of highly connected nodes, while the majority of nodes have few
      connections. The highly connected nodes serve as hubs that affect many other
      nodes. Such hubs have key roles in the network. In yeast cells, for example,
      deletion of highly connected proteins is associated with increased lethality,
      compared to deletion of less connected proteins. This suggests the biological
      relevance of networks. Moving down in the network structure, there may be sub
      networks or modules with specific functions. These modules may be further
      dissected to analyze individual nodes. In the context of DNA microarray studies
      of complex diseases, gene-interaction networks may contain modules of co
      regulated or interacting genes that have distinct biological functions. Such
      modules may be linked to specific gene polymorphisms, transcription factors,
      cellular functions and disease mechanisms. Genes that are reliably active only in
      the context of their modules can be considered markers for the activity of the
      modules and may thus be promising candidates for biomarkers or therapeutic
      targets. This review aims to give an introduction to network theory and how it
      can be applied to microarray studies of complex diseases.

PMID- 17022742
TI  - [Efalizumab--therapy of moderately severe to severe plaque-psoriasis in the
      dermatologist's practice].
AB  - Psoriasis is a chronic immune-mediated skin disease with highly variable patterns
      of presentation, both between patients and in individuals over time. Its course
      can be influenced by various triggers. Since there is no cure for psoriasis,
      patients with moderate-to-severe plaque-type psoriasis often require lifelong
      therapy to control their disease. Traditional approaches such as cyclosporine or
      methotrexate are problematic for long-term use because of organ toxicity, other
      side effects, drug interactions and a loss of efficacy over time. Efalizumab is a
      recombinant monoclonal IgG1-antibody, approved in Germany for the management of
      moderate-to-severe plaque-type psoriasis. Its efficacy and safety have been
      demonstrated in clinical trials with thousands of patients,especially with regard
      to long-term therapy. Therefore, a change of paradigm from the traditional
      therapy of inflammatory episodes to continuous control of psoriasis seems
      possible. This supplement deals with practical aspects of using efalizumab in the
      outpatient setting.

PMID- 17022744
TI  - Hypoalbuminemia is an important risk factor of hypotension during hemodialysis.
AB  - Hypotension during hemodialysis (HD) is an important problem in patients on HD.
      To investigate the risk factors that contribute to the hypotension during HD, we
      compared background factors of hypotensive (HP) patients during HD. Among 58
      patients undergoing HD in Tamura Memorial Hospital, 12 patients could not
      continue full HD because of hypotension. We compared the data of ultrafiltration
      volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea
      nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood
      glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP
      patients (HP group; n=12) and sex- and age-matched control patients (NP group;
      n=12). There were no significant differences of age, sex, and duration of HD
      between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP
      group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%,
      p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP
      group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP
      3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of
      ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2
      groups. There is a significant negative correlation between changes of systolic
      blood pressure (delta systolic blood pressure) and serum albumin in these
      patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia
      is a major risk factor of hypotension during HD.

PMID- 17022745
TI  - Intradialytic changes of serum magnesium and their relation to hypotensive
      episodes in hemodialysis patients on different dialysates.
AB  - Magnesium is a crucial mineral, involved in many important physiological
      processes. Magnesium plays a role of maintaining myocardial electrical stability
      in hemodialysis patients. Intradialytic hypotension is a common complication of
      dialysis and it is more common with acetate dialysate. The significance of the
      intradialytic changes of magnesium and their relation to parathyroid hormone
      (PTH) level and calcium changes during dialysis, and their relation to
      hypotensive episodes during dialysis are interesting. The aim of this work is to
      investigate the intradialytic changes of serum magnesium in chronic hemodialysis
      patients with different hemodialysis modalities and the relation to other
      electrolytes and to PTH, and also the relation to intradialytic hypotension. The
      present study was conducted on 20 chronic renal failure patients. All patients
      were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate
      (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate
      based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH
      during a hemodialysis session, the same patients were shifted to bicarbonate
      dialysis (group II). All patients were subjected to full history and clinical
      examination, predialysis laboratory assessment of blood urea nitrogen (BUN),
      serum creatinine, albumin, and hemoglobin, serial assessment of magnesium,
      calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis
      session, 2 hr later, and at the end of the session, blood pH, and
      electrocardiogram (ECG) presession and postsession. All patients were urged to
      fix their dry weight, diet, and current medications. None of the patients had
      diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on
      magnesium-containing drugs or previously parathyroidectomized. Hemodialysis
      sessions were performed by volumetric dialysis machines using the same
      electrolyte composition. Magnesium level significantly increased in the
      bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1,
      and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased
      in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33
      mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate
      group (p=0.024) but not in the acetate group. Phosphorus level significantly
      decreased in both acetate and bicarbonate groups. PTH level did not significantly
      change in either group, p value > or =0.05. Blood pH significantly increased,
      changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG
      showed no significant changes during sessions with either type of dialysate.
      Hypotension was significantly higher in group I compared with group II (p=0.01),
      and this hypotension was positively correlated with a decrease in serum magnesium
      level in group I. Intradialytic changes in serum magnesium have no correlation
      with intradialytic changes in serum calcium or with PTH level. However, it was
      significantly correlated with hypotension during the dialysis session, especially
      with acetate dialysate. Further investigations are needed to determine whether or
      not this is true in patients using bicarbonate dialysis.

PMID- 17022746
TI  - Coagulation cascade.
AB  - The coagulation cascade is now recognized to be a series of proteolytic events
      mainly localized to the surface of activated platelets. Once platelets become
      activated by exposure to activated endothelium, they release mediators such as P
      selectin and von Willebrand factor that promote microvesicle formation and
      platelet adherence. The microvesicles fuse with the activated platelet membrane,
      providing tissue factor and its ligand, factor VIIa. Clotting factors bind to
      adjacent receptors on the membrane, enabling the cascading proteolytic cleavages
      of zymogens to active enzymes, culminating in thrombin generation. Fibrin
      formation thus occurs in the sheltered environment of the platelet membrane,
      where it is localized to the site of injury and protected from circulating
      inhibitors.

PMID- 17022747
TI  - Achieving targets for bone and mineral metabolism: the impact of cinacalcet HCl
      in clinical practice.
AB  - Achieving the K/DOQI targets for bone and mineral metabolism has proven difficult
      with the use of vitamin D analogues and phosphate binders. The introduction of
      cinacalcet HCl provided a new tool with a novel therapeutic mechanism of action.
      The purpose of this study was to evaluate the effect of the introduction of
      combination algorithm for managing secondary hyperparathyroidism (SHPT) on
      phosphorus, calcium, and biointact parathyroid hormone (PTH). The 61 patients who
      dialyzed in the facility from January 2004 (baseline) and who remained in the
      facility as of April 2005 (follow-up) were included in the study. In the baseline
      period, 37 (61%) of the patients received paricalcitol at some time during the 3
      month observation period. In the follow-up period, 19% or 31% of the patients
      received cinacalcet HCl. Of those not receiving cinacalcet HCl, 67% had PTH at or
      below target, 17% were felt to be noncompliant with oral meds, 7% had low
      calcium, and 10% either could not get the medication or were not switched to the
      combination pathway. Compared with the baseline period, the percent of patients
      who met the PTH target increased from 19.7% to 37.7%, p<0.05. The percent of
      patients meeting all 4 targets increased from 14.8% to 24.6%, although this did
      not reach statistical significance. The introduction of cinacalcet HCl into a
      treatment algorithm for management of SHPT resulted in a significant increase in
      the percentage of patients achieving the PTH target while maintaining the other
      mineral metabolism targets.

PMID- 17022748
TI  - Effect of supportive extracorporeal treatment in liver transplantation recipients
      and advanced liver failure patients.
AB  - Recently, continuous venovenous hemodiafiltration (CVVHDF) and plasmapheresis
      (PF) were suggested as supportive therapy options in combination with standard
      treatment in advanced liver failure. The aim of this study was to analyze the
      effects of supportive extracorporeal treatment (SET) in a group of patients with
      advanced hepatic failure. A total of 25 patients (7 women, 18 men; mean age,
      39.3+/-15.4 years; 13 were transplant recipients [6 women, 7 men; mean age,
      37.7+/-16.9 years]) were included. All patients were in hepatic coma and
      receiving standard coma and liver failure management when they received SET.
      Number of SET sessions; levels of serum blood urea nitrogen, creatinine, albumin,
      calcium, phosphorus, ammonia, alanine and aspartate aminotransferase, and
      total/conjugated bilirubin; and prothrombin times (PTT) before and after SET were
      recorded retrospectively. 7.7+/-7.9 SET sessions were performed. Thirteen liver
      transplant recipients required SET for an average of 9.7+/-8.3 days after
      transplantation. Serum ammonia and bilirubin levels were lower after termination
      of supportive therapy when compared with initial levels (p<0.0001 and p<0.005
      respectively). During follow-up, hepatic encephalopathy and liver failure
      resolved in 11 patients, while 14 patients (7 transplant recipients) died. There
      was no significant difference between patients in either group except that PTT
      was shorter in patients who survived (p<0.01). Further analyses revealed that in
      surviving patients, ammonia clearance was higher (p<0.01). In patients with
      advanced liver failure, or liver transplants, CVVHDF and/or PF could be
      supportive options combined with standard treatment.

PMID- 17022750
TI  - In search of an advance directive that works for end-stage renal disease
      patients.
AB  - Although loss, disability, and death are constant possibilities for any end-stage
      renal disease patient, very few have planned for the last of life. Currently
      available Advance Directives (ADs) are refusal of specific therapies in only
      specific but nebulous circumstances. They fail to provide positive guidance for a
      patient's remaining time. Without addressing goals, quality of life,
      reversibility of medical problems, and desired end-of-life (EOL) care, such ADs
      are useless. End-stage renal disease providers are generally untrained and
      unsupported in offering guidance. Financial, emotional, and structural factors
      collude to justify ignoring EOL planning. Several alternative ADs are offered,
      along with a goal-directed approach to EOL counseling for patients and staff.

PMID- 17022749
TI  - Cystatin C in critically ill patients treated with continuous venovenous
      hemofiltration.
AB  - Assessment of residual renal function in critically ill patients with acute renal
      failure (ARF) treated with continuous venovenous hemofiltration (CVVH) is
      difficult. Cystatin C (CysC) is a low-molecular-weight protein (13.3 kDa) removed
      from the body by glomerular filtration. Its serum concentration has been
      advocated for assessment of renal function in patients with kidney disease. To
      investigate whether the removal of CysC by CVVH is likely to influence its serum
      concentration, concentrations of CysC were measured in 3 consecutive samples in
      18 patients with oliguric ARF treated with CVVH (2 L/hr). Samples were taken from
      the afferent and efferent blood lines and from the ultrafiltrate line.
      Concentrations of CysC did not change during the time interval studied. The mean
      serum concentrations of CysC were 2.25+/-0.45 mg/L in the afferent and 2.19+/
      0.56 mg/L in the efferent samples (NS); ultrafiltrate concentrations of CysC were
      1.01+/-0.45 mg/L. The sieving coefficient of CysC was 0.52+/-0.20; the clearance
      of CysC was 17.3+/-6.6 mL/min; and the quantity of CysC removed averaged 2.13
      mg/hr. During CVVH (2 L/hr), the quantity of CysC removed is less than 30% of its
      production and no rapid changes in its serum concentration are observed.
      Therefore, CVVH (2 L/hr) is unlikely to influence serum concentrations of CysC
      significantly, which suggests that it can be used to monitor residual renal
      function during CVVH.

PMID- 17022751
TI  - What, me grieve? Grieving and bereavement in daily dialysis practice.
AB  - We seldom consider the terms "grieving" or "bereavement" until faced with an
      empty dialysis chair. But loss (bereavement) and the process we go through to
      heal from that loss (grieving) begin with a patient's first puff of edema or
      abnormal creatinine, and continue throughout the course of an illness. By
      recognizing the symptoms and developing the tools to deal with loss, we will
      enrich the value of our practice for ourselves and those with whom we work.

PMID- 17022752
TI  - Comparisons of Kt/V evaluated using an online method and calculated from urea
      measurements in patients on intermittent hemodialysis.
AB  - Kt/V(urea) (Kt/V) depends on the method applied for its evaluation. Our aim was
      to compare Kt/V obtained using the conductivity online method and that calculated
      from urea measurements. Studies were carried out in 40 patients. A stable
      dialysis schedule was maintained during the study. Online Kt/V was measured every
      week or 4 consecutive months. Single pool Kt/V (spKt/V) was calculated from urea
      estimations in the fourth week of the first month and in the last week of the
      fourth month of studies, using the formulas: (1)spKt/V = -ln(Ct/Co), where Ct is
      the postdialysis urea concentration obtained at the end of dialysis, Co the
      predialysis urea concentration obtained before the start of the blood pump;
      (2)spKt/V = -ln(R - 0.008 x t - f x UF/W), where R is the Ct/Co, t the duration
      of HD session, f=1.0, UF is the ultrafiltration volume (l), W is the body weight
      after the HD session; and (3)spKt/V + -ln(R - 0.008 x t) + (4 - 3.5 x R) x UF/W.
      The equilibrated Kt/V (eKt/V) was calculated as (3)spKt/V - {0.47 x
      [(3)spKt/V]/t} + 0.02. Correlation analysis was performed between all obtained
      Kt/V. Weekly online Kt/V was stable during 4 months of studies. In the first
      month, the respective values of online Kt/V, (1)spKt/V, (2)spKt/V, (3)spKt/V, and
      eKt/V were 1.15+/-0.14, 1.16+/-0.14, 1.38+/-0.17, 1.36+/-0.20, and 1.22+/-0.13.
      In the fourth month, these values were 1.17+/-0.14, 1.16+/-0.17, 1.38+/-0.22,
      1.35+/-0.20, and 1.22+/-0.18. The respective values of Kt/V, estimated in the
      first and fourth month, were not different and showed a positive correlation: the
      highest one occurred between online Kt/V estimated at the indicated study periods
      (r=0.713, p=0.0000). Online Kt/V was significantly lower than (2)spKt/V,
      (3)spKt/V, and eKt/V. Correlation coefficients between online Kt/V, spKt/V, and
      urea reduction ratio did not exceed 0.490. Our studies show that Kt/V obtained
      using online monitoring indicates a lower intermittent hemodialysis adequacy that
      those calculated from urea measurements. This difference has to be remembered in
      application of results to clinical practice.

PMID- 17022753
TI  - Metastatic pulmonary calcification in a dialysis patient: case report and a
      review.
AB  - A 19-year-old male presented with chest pain and dyspnea. He was anephric
      following nephrectomy for focal segmental glomerulosclerosis, had a subsequent
      failed transplant, and had been dialysis dependent for 3 years. Workup revealed
      hyperparathyroidism and an abnormal chest X-ray and computed tomography scan,
      significant for massive extra-skeletal pulmonary calcification. A markedly
      abnormal Technitium99 methylene diphosphonate (Tc99m-MDP) bone scan confirmed the
      clinical suspicion of metastatic pulmonary calcification. Metastatic pulmonary
      calcification (MPC) is common, occurring in 60% to 80% of dialysis patients on
      autopsy and bone scan series. It may lead to impaired oxygenation and restrictive
      lung disease. Typically, the calcium crystal is whitlockite rather than
      hydroxyapatite, which occurs in vascular calcification. Four major predisposing
      factors may contribute to MPC in dialysis patients. First, chronic acidosis
      leaches calcium from bone. Second, intermittent alkalosis favors deposition of
      calcium salts. Third, hyperparathyroidism tends to cause bone resorption and
      intracellular hypercalcemia. Finally, low glomerular filtration rate can cause
      hyperphosphatemia and an elevated calcium-phosphorus product. There may be other
      factors. Some authors suggest that the incidence of MPC in recent years may be
      lower due to improved dialysis techniques. The diagnosis is confirmed by biopsy,
      but can be suspected by typical findings on a Tc99m-MDP bone scan. Therapy is
      limited to ensuring adequate dialysis, correcting calcium-phosphorus product, and
      hyperparathyroidism; discontinuing vitamin D analogues may help. Conflicting
      reports show that transplantation may either improve or worsen the situation. MPC
      should be considered in dialysis patients who have characteristic abnormal chest
      radiography and/or pulmonary symptoms.

PMID- 17022754
TI  - [Diagnostics of fungal infections of the eye and of its adnexa].
AB  - The spectrum of fungal infections of the eye and of its adnexa is presented with
      respect to their clinical pictures as well as to their laboratory diagnostic
      monitoring. The various types of localisation are different in their
      symptomatologies, in their risk factors and in their aetiology.

PMID- 17022755
TI  - [Keratomycosis due to Cylindrocarpon lichenicola].
AB  - Two independent males acquired keratomycosis at a few months interval. The
      culturally proven pathogen was Cylindrocarpon lichenicola (C. Massal) D.
      Hawksworth. For one patient Clematis plants were suspected of source of
      infection. Both patients did not remember traumata; they had no contact with each
      other, and their residences were far apart. One patient was treated with
      voriconazole locally and systemically for 12 weeks, the other patient with
      amphotericin B locally for 6 weeks. Both treatment regimens were successful.
      Cylindrocarpon lichenicola is characterised by keratinolytic properties.
      Following molecular-genetic studies the pathogen was recently reclassified as
      Fusarium lichenicola.

PMID- 17022756
TI  - [Optical brighteners in fungal diagnostics].
AB  - Fluorescent staining using optical brighteners (diaminostilbenes) affords the
      semispecific and rapid detection of fungal elements in clinical specimens. After
      yielding a first hint of mycosis, the identification of the involved fungal genus
      is often desirable in cases when culture proves unsuccessful. In such cases,
      immunohistochemistry or in situ hybridisation may further the diagnosis with
      respect to establish an appropriate therapy.

PMID- 17022757
TI  - [Impact of antifungal prophylaxis on the gastrointestinal yeast colonisation in
      patients with haematological malignancies].
AB  - Patients with haematological malignancies are at high risk for developing
      invasive Candida infections. They are often colonised with Candida spp. in the
      gastrointestinal (GI) tract. In order to prevent infection, the prophylactic use
      of antifungal agents has been established. The widespread use of fluconazole may
      lead to the emergence of resistant Candida isolates. We studied the yeast
      colonisation of the GI tract in patients with haematological malignancies
      receiving antifungal prophylaxis (AP) in comparison with healthy controls. The
      study cohort included 46 neutropenic patients with 52 stool samples under 52
      episodes of AP and 110 healthy controls. The patients received amphotericin B
      orally (n = 8), amphotericin B and fluconazole (n = 7), amphotericin B and
      itraconazole (n = 5), fluconazole orally (n = 15) and itraconazole orally (n =
      17). Yeasts were cultured from the stool samples of 63.5% of the patients and 60%
      of the controls with a mean yeast load of 1.6 x 10(3) and 0.4 x 10(3) cfu g(-1),
      respectively (P = 0.045). Patients and controls had a low faecal yeast load of
      10(3) to 10(4) cfu g(-1) in 19.3% and 37.3%, respectively (P = 0.021), and yeast
      overgrowth of >10(5) cfu g(-1) in 28.9% and 10.9%, respectively (P = 0.004). The
      rate of Candida albicans was 32.6% and 54.1% in the patients and controls,
      respectively (P = 0.021). The rates of fluconazole-resistant yeast species were
      higher in the patient group than in the control group: C. glabrata 20.9% vs.
      11.7% (P = 0.168), C. krusei 25.6% vs. 4.7% (P = 0.001). Not a single patient
      under AP suffered from proven or probable invasive candidosis. In conclusion,
      oral AP in haematological patients resulted in a higher colonisation rate with
      fluconazole-resistant Candida species but efficiently prevented invasive
      candidosis.

PMID- 17022758
TI  - [Ultrastructural characters defining the terms 'yeast cell', 'pseudomycelium' and
      'true mycelium' in Candida albicans].
AB  - The discrimination of the morphological elements, 'yeast cell', 'pseudomycelium'
      and 'true mycelium' is indispensable in the mycological and histopathological
      diagnostics of fungal infections caused by Candida albicans. However, precisely
      defined distinctive criteria are lacking in the medical mycological literature.
      Such criteria based upon electron microscopical studies of the cell wall, are
      described.

PMID- 17022759
TI  - Zeocin resistance as a dominant selective marker for transformation and targeted
      gene deletions in Candida glabrata.
AB  - Many of the genetic tools used to generate gene knockouts in Candida glabrata
      exploit auxotrophic markers but this is not suitable for use with clinical
      strains. Antibiotic resistance markers, however, allow one to target genes to be
      deleted without any prior genetic manipulation of clinical isolates. Such
      antibiotic selection markers have been widely reported for the manipulation of
      Saccharomyces cerevisiae. However, very few antibiotic resistance markers have
      been shown to be useful in C. glabrata. Here, we report the use of Zeocin
      resistance (ZeoR), encoded by the ble gene from Streptoalloteichus hindustanus,
      as a new positive selection marker for the genetic manipulation of C. glabrata
      including clinical strains that we show are significantly more sensitive to
      Zeocin than to G418. The potential of the ZeoR marker for targeted gene
      disruption in C. glabrata was confirmed by constructing deletions of the ADE2 in
      both a laboratory and a clinical strain of C. glabrata, using both short (90 bp)
      and long (400 bp) homology cassettes.

PMID- 17022760
TI  - Study of the ITS region in an atypical isolate and comparison with six species of
      Microsporum.
AB  - Microsporum species are a frequent cause of cutaneous mycoses in humans. Atypical
      strains of Microsporum can sometimes be difficult to identify with conventional
      methods. Recently, we have obtained a Microsporum isolate with atypical
      morphology and special nutritional requirements (Microsporum CHUS-126-02). As
      several molecular techniques have been developed for the identification of fungi,
      we analysed six Microsporum species (M. canis, M. gypseum, M. gallinae, M. nanum,
      M. ferrugineum and M. persicolor) in order to compare them with our isolate, by
      using polymerase chain reaction-restriction enzyme analysis (PCR-REA). We studied
      the nucleotide sequence of the internal transcribed spacer regions from the
      nuclear DNA encoding for the ribosomal domain. Digestion with MvaI and EcoRI
      endonucleases obtained specific patterns for M. gypseum, M. gallinae, M. nanum
      and M. persicolor. Microsporum canis, M. ferrugineum and Microsporum CHUS-126-02
      yielded the same patterns. Based on these results and phenotypic criteria, we
      classified our atypical isolate as M. canis.

PMID- 17022761
TI  - Fluconazole and itraconazole susceptibilities of Candida spp. isolated from
      oropharyngeal specimens and blood cultures of paediatric haematology/oncology
      patients.
AB  - This study examined the in vitro susceptibilities to fluconazole and itraconazole
      of isolates of Candida spp. from surveillance oropharyngeal specimens and blood
      cultures from paediatric patients with malignancy. The species distribution of
      100 isolates from oropharyngeal specimens was C. albicans 86%, C. glabrata 7%, C.
      lusitaniae 4%, C. parapsilosis 2% and C. tropicalis 1%. From a total of nine
      isolates from blood cultures the species distribution was C. albicans 33.3%, C.
      parapsilosis 33.3 % and C. guilliermondii 33.3%. Only three of the oropharyngeal
      isolates were resistant to fluconazole (MIC > or = 64 mg l(-1)) and only two were
      resistant to itraconazole (MIC > or = 1 mg l(-1)). None of the blood culture
      isolates was resistant to either agent. At this centre, C. albicans is the
      predominant species from oropharyngeal specimens, but non-albicans Candida
      species predominate in blood cultures. Although resistance to fluconazole and
      itraconazole is rare at present, continued surveillance is warranted to monitor
      trends in species distribution and antifungal susceptibility.

PMID- 17022762
TI  - Torsade de pointes induced by systemic antifungal agents: lessons from a
      retrospective analysis of published case reports.
AB  - Torsade de pointes (TdP) is a potentially fatal arrhythmia that might be
      associated with systemic antifungal agent (SAFAs) administration. The objective
      of this study was to investigate all published reports on TdP induced by SAFAs in
      order to characterise this association. Each original report was analysed for the
      presence of risk factors for TdP: female gender, structural heart disease,
      electrolyte imbalance, concomitant use of a QT interval prolonging agent which
      SAFA inhibits its liver metabolism, liver cirrhosis, renal failure and more.
      Naranjo probability scale for adverse drug reactions was applied for every full
      report. Twenty-one reports on 28 patients were analysed. All patients survived.
      Most patients (25/28; 89.2%) used one or more agents that might have prolonged
      the QT interval and their liver metabolism might have been inhibited by SAFA.
      Female gender was the second most common risk factor for TdP (20/28; 71.4%). All
      patients, including female patients, had one or more risk factors for TdP prior
      to SAFA administration. According to Narajno probability scale, there was no
      definite association between TdP and SAFA in any report. SAFA alone might seldom
      trigger TdP. We wish to raise the level of awareness of risk factors for TdP
      prior to SAFA administration and for concomitant use of other dysrhythmogenic
      agents in particular.

PMID- 17022763
TI  - A 5-year (2000-2004) epidemiological survey of Candida and non-Candida yeast
      species causing vulvovaginal candidiasis in Graz, Austria.
AB  - Vulvovaginal candidasis (VVC) is a common disease. The majority of cases is
      caused by Candida albicans, but in recent years an increase has been observed in
      the frequency of non-albicans Candida infections, especially due to C. glabrata
      and C. tropicalis. The aim of the study was to assess the prevalence of non
      albicans Candida infections in patients suffering from VVC. Therefore, the
      statistical data of culture-confirmed VVC ascertained at the Institute of Hygiene
      (Medical University Graz) have been studied. Altogether, 10,463 samples from
      patients with vulvovaginal complaints were analysed in the years 2000-2004, a
      number of 3184 proved to be culture-positive for yeast. Candida albicans was the
      most prevalent cause in 87.9% of all cases. Non-albicans Candida yeast were
      detected in 12.1%, mainly C. glabrata and Saccharomyces cerevisiae. During a 1
      year period 185 patients showed more than one episode of VVC. Patients aged 21-40
      years were significantly more prone to suffer from VVC compared with other age
      related groups.

PMID- 17022764
TI  - Perniosis-like tinea corporis caused by Trichophyton verrucosum in cold-exposed
      individuals.
AB  - Trichophyton verrucosum is a zoophilic infectious agent causing 98% of the
      dermatophytic infections of cattle. Transmission to humans has, until recently,
      been rare. One reason for an increase of infection in humans and animals seems to
      be the decrease in immunisation of cattle. We report on three cases of pertinent
      human infections with disseminated, sharply defined, bluish red, partly
      oedematous nodules and plaques in particular not only on the thighs, but also on
      the trunk and arms. Two of our patients work with farm animals. The third one
      works as an assistant in a butcher shop, but lives on a cow farm. All three
      patients are often exposed to the cold. In all three cases T. verrucosum was
      detected by culture. Tinea corporis was histologically confirmed in two patients.
      Based on the microbiological results, we began a combined systemic and local
      antimycotic therapy with fluconazole 50 mg day(-1) in two patients, itraconazole
      100 mg day(-1) in one patient p.o. combined with topical ciclopiroxolamine. All
      patients were cured. Dermatophytosis caused by T. verrucosum can, under certain
      circumstances, such as frequent exposure to cold or a long-term corticosteroid
      therapy, mimic the characteristic clinical picture of perniosis, as we
      demonstrate here.

PMID- 17022765
TI  - Tinea capitis among rural school children of the district of Magude, in Maputo
      province, Mozambique.
AB  - The study was carried out in two rural primary schools of the District of Magude,
      the largest district of Maputo Province in 2001. The prevalence of tinea capitis
      in each school was 11.6% (49/422) and 6.8% (18/263) and affected predominantly
      male children. The most common dermatophytes isolated from both schools were
      Microsporum audouinii. However, Trichophyton mentagrophytes was also found to be
      an important causal agent of tinea capitis in the District of Magude. Although
      the prevalence of tinea capitis found in our study is relatively high compared to
      previous cross-sectional studies carried out in Mozambique, it is still closely
      related to the prevalence rates reported for African countries. Tinea capitis
      continues to be an important public health issue in Mozambique, particularly in
      primary school setting.

PMID- 17022766
TI  - Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive
      Care Unit.
AB  - The use of oral nystatin to prevent fungal colonisation and infection in neonates
      in the Neonatal Intensive Care Unit (NICU) is still an open question and not yet
      recommended as a standard of care. To determine whether prophylactic oral
      nystatin results in a decreased incidence of invasive candidiasis in the newborn
      infants, a total of 3991 infants were divided randomly into two groups. Group A
      infants (n = 1995), only those neonates who were identified as yeast carriers
      (oral moniliasis) were treated with oral nystatin. Group B infants, all neonates
      who were admitted to the unit received oral nystatin, was routinely administered
      three times a day. Group A was divided into groups A1 and A2 (who were treated
      only if identified as yeast carriers). Urine and rectal cultures were taken on
      admission and then weekly thereafter. There were 215 (14.2%), 27 (5.6%) and 36
      (1.8%) patients positive for invasive candidiasis in groups A1, A2 and B
      respectively. Oral nystatin prophylaxis significantly reduced the invasive
      candidiasis (P = 0.004) in extremely low-birth weight (ELBW) and very low-birth
      weight (VLBW) infants. Prophylactic administration of oral nystatine to the ELBW
      and VLBW infants results in a decreased risk of invasive candidiasis.

PMID- 17022767
TI  - Respiratory allergies in Venezuela: are fungi responsible?
AB  - Exposure to fungi in the indoor environment may trigger hypersensitivity to a
      variety of fungi and is known to be an influencing factor in allergic rhinitis
      and asthma. A wide list of airborne fungal spores and dust containing fungi have
      been described for different environments; however, their clinical relevance is
      seldom clear. In this survey we measure levels of fungi indoor and outdoor of
      domestic dwellings of 10 patients with known chronic allergic respiratory disease
      to fungi. To measure hypersensitivity to fungi, Prick (sensitivity to fungi),
      RAST (specific serum IgE levels) and PAR (persistent allergic rhinitis) severity
      are assessed in relation to fungal load in the environment. Only association of
      PAR and indoor fungal load were found to be significant (P = 0.1648). No direct
      causality with sensitivity to the amount of exposure, or a hypersensitivity to a
      specific fungal genus could be established. There is still no consensus on the
      most relevant methods for measuring personal exposure and 'no safe levels' have
      been established yet.

PMID- 17022768
TI  - Prevalence of dermatophytosis in junior secondary schoolchildren in Ogun State,
      Nigeria.
AB  - A total of 2772 randomly selected junior secondary school pupils (aged 8-14) from
      60 schools were examined for dermatophytic infections by direct microscopy and
      culture-based laboratory diagnostic methods. Of these, 641 (23.21%) had
      dermatophytosis. Out of these, 376 (13.56%) were male while 265 (9.56%) were
      female. Aetiological agents identified with infection were Microsporum canis
      (30.19%), Microsporum audouinii (32.92%), Trichophyton interdigitale (14.37%),
      Trichophyton soudanense (9.73%) and Trichophyton tonsurans (12.05%). Most of the
      dermatophytes encountered were anthropophilic species. Microsporum canis was the
      only zoophilic dermatophyte. Differences were not observed in infection pattern
      for all the different geo-political zones that make up the state. The head and
      the skin of the students were more frequently infected than the nails and toes.
      Infection frequency increased steadily up to age 11 after which it drastically
      decreased.

PMID- 17022769
TI  - Isolation of Exophiala dermatitidis from endotracheal aspirate of a cancer
      patient.
AB  - Exophiala (Wangiella) dermatitidis is a melanised (darkly pigmented) yeast-like
      organism that has been reported from the environment and wild animals. The
      organism is a frequent coloniser of lungs of patients with cystic fibrosis and
      causes occasional disseminated phaeohyphomycosis and fungaemia. Exophiala
      dermatitidis is distributed worldwide, but cerebral cases are restricted to East
      Asia. We report a case of 54-year-old Qatari female patient with a known history
      of cancer, suffering from pulmonary disorder. Culture of endotracheal aspirate
      revealed the growth of E. dermatitidis concomitant with Candida krusei. The final
      diagnosis of E. dermatitidis and attribution to genotype B was achieved by
      sequencing the rDNA internal transcribed spacer (ITS) region. The present case
      concerns a pulmonary colonisation by E. dermatitidis, similar to that commonly
      seen in cystic fibrosis patients. For the detection of E. dermatitidis in
      clinical specimens culturing techniques are required. The patient finally expired
      with persistent cancer and C. krusei fungaemia. Review of literature and listing
      of E. dermatitidis cases published after 1992 show a sharp increase in clinical
      cases during the 1990s.

PMID- 17022770
TI  - Yeast associated with human infections in south-eastern Nigeria.
AB  - A total of 1921 specimens from nine clinical sources were examined by direct
      microscopy and culture to recover yeast associated with human infection.
      Identification of yeast was based on their carbon assimilation patterns, using
      API 20C AUX and ID 32 C (bioMerieux, France) commercial kits. A total of 178
      specimens (9.3%) were positive for yeast. Most of the yeast isolates were
      recovered from urine samples and genital swabs. Prevalence was significantly
      higher in women (14.7%) than in men (1.4%) (P < 0.05). The age group 21-30 years
      recorded the highest prevalence of yeast infection (65.2%) followed by age group
      11-20 years (16.9%) and > 40 years (9.0%). When genital samples were considered,
      prevalence was significantly higher in the age group 21-30 years than that in
      older ones (P < 0.05). Isolates recovered included seven species of Candida and
      Trichosporon inkin. C. albicans accounted for the highest number of isolates
      (128) followed by C. tropicalis (23) and C. parapsilosis (9). Two isolates each
      of C. famata and C. norvegensis were recorded and are reported for the first time
      in Nigeria. The two isolates of T. inkin were recovered from perianal lesions and
      are also reported for the first time from Nigeria. C. albicans, C. glabrata, C.
      parapsilosis and C. krusei were found to be the most common yeast species that
      act as agents of human disease in south-eastern Nigeria.

PMID- 17022771
TI  - Absence of sunburn in lesions of pityriasis versicolor alba.

PMID- 17022772
TI  - Pityriasis versicolor prevalence by age and gender.

PMID- 17022773
TI  - Chronic refractory phaeohyphomycosis: successful treatment with posaconazole.

PMID- 17022774
TI  - Detection of Candida species by PCR in self-collected vaginal swabs of women
      after taking antibiotics.
AB  - Women undergoing antibiotic treatment can develop vulvovaginal candidiasis. This
      study evaluated polymerase chain reaction (PCR) for the detection of Candida
      species in comparison with the conventional laboratory culture methods in samples
      from women with and without symptoms of postantibiotic candidiasis. The self
      collected vaginal swabs from 90 women, with no recent symptoms of vulvovaginal
      candidiasis (VVC), who were prescribed antibiotics for non-genital infection were
      evaluated 8 days after completion of antibiotics and/or at the time of developing
      symptoms of VVC. Broad-spectrum fungal PCR was performed on extracted DNA from
      each sample. Overall PCR detected four additional Canidida albicans, three
      Candida parapsilosis and one Candida tropicalis when compared with culture. All
      but one case additionally detected by PCR were found in patients with no VVC
      symptoms. PCR, although more sensitive than conventional culture methods, in this
      small number of cases, has not been able to detect Candida species in
      significantly more patients with symptoms suggestive of candidiasis. The results
      of this study may indicate that other agents including other yeast species may be
      responsible for symptoms of postantibiotic vulvovaginitis.

PMID- 17022776
TI  - Anosognosia after stroke: assessment, occurrence, subtypes and impact on
      functional outcome reviewed.
AB  - PURPOSE: This review provides an update on recent research findings concerning
      the methods used in the assessment of anosognosia, the occurrence and subtypes of
      anosognosia, the association between anosognosia and neglect, and the impact of
      anosognosias on functional outcome. METHODS: A systematic review covering the
      period from 1995 to 2005 was carried out on reports drawn from electronic
      databases (MEDLINE, PSYCHLIT) and identified from the references in these
      reports. Twenty-seven articles met the selection criteria. RESULTS: The results
      of this review are in line with previous findings in the following respects:
      anosognosia was more often associated with right hemisphere damage, neglect and
      anosognosia co-occurred, and anosognosia had predictive value on poor functional
      outcome. The variation in the methods used in the assessment of anosognosia,
      patient samples and assessment times influence the occurrence rates and the
      predictive value of anosognosia, which might undermine the generalizability of
      the results. CONCLUSIONS: More homogeneous patient samples and consistency in the
      assessment methods and evaluation times would facilitate comparisons of the
      occurrence and the impact of anosognosia on functional outcome. New methods need
      to be developed for the assessment of anosognosia. These new methods should take
      account of the subtypes of anosognosia both at verbal and at non-verbal levels.

PMID- 17022777
TI  - Total direct cost, length of hospital stay, institutional discharges and their
      determinants from rehabilitation settings in stroke patients.
AB  - BACKGROUND: Length of hospital stay (LOHS) is the largest determinant of direct
      cost for stroke care. Institutional discharges (acute care and nursing homes)
      from rehabilitation settings add to the direct cost. It is important to identify
      potentially preventable medical and non-medical reasons determining LOHS and
      institutional discharges to reduce the direct cost of stroke care. AIM: The aim
      of the study was to ascertain the total direct cost, LOHS, frequency of
      institutional discharges and their determinants from rehabilitation settings.
      METHODOLOGY: Observational study was conducted on 200 stroke patients in two
      rehabilitation settings. The patients were examined for various socio
      demographic, neurological and clinical variables upon admission to the
      rehabilitation hospitals. Information on total direct cost and medical
      complications during hospitalization were also recorded. The outcome variables
      measured were total direct cost, LOHS and discharges to institutions (acute care
      and nursing home facility) and their determinants. RESULTS: The mean and median
      LOHS in our study were 34 days (SD = 18) and 32 days respectively. LOHS and the
      cost of hospital stay were significantly correlated. The significant variables
      associated with LOHS on multiple linear regression analysis were: (i) severe
      functional impairment/functional dependence Barthel Index < or = 50, (ii) medical
      complications, (iii) first time stroke, (iv) unplanned discharges and (v)
      discharges to nursing homes. Of the stroke patients 19.5% had institutional
      discharges (22 to acute care and 17 to nursing homes). On multivariate analysis
      the significant predictors of discharges to institutions from rehabilitation
      hospitals were medical complications (OR = 4.37; 95% CI 1.01-12.53) and severe
      functional impairment/functional dependence. (OR = 5.90, 95% CI 2.32-14.98).
      CONCLUSION: Length of hospital stay and discharges to institutions from
      rehabilitation settings are significantly determined by medical complications.
      Importance of adhering to clinical pathway/protocol for stroke care is further
      discussed.

PMID- 17022778
TI  - ApoE genotype and cognition after subarachnoid haemorrhage: a longitudinal study.
AB  - OBJECTIVES: To investigate the effect of the apolipoprotein epsilon4 allele on
      cognitive functions after aneurysmal subarachnoid haemorrhage (SAH) in a
      longitudinal study. MATERIALS AND METHODS: Performances of 19 patients with and
      27 patients without the epsilon4 allele were compared on eight cognitive test
      variables measured 1-4.5 years and 12-15 years after SAH. RESULTS: In the
      baseline examination, epsilon4 patients scored worse than non-epsilon4 patients
      on verbal fluency (P < 0.05). In the follow-up, a visual memory task and
      interference in colour naming showed more pronounced impairments from baseline in
      epsilon4 carriers than in non-carriers. CONCLUSION: Presence of the epsilon4
      allele poses a minor risk for late cognitive impairment after the subacute phase
      of aneurysmal SAH.

PMID- 17022779
TI  - ACE I/D polymorphism in different etiologies of ischemic stroke.
AB  - OBJECTIVES: Data concerning an association between angiotensin-converting enzyme
      (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain
      inconsistent. Results of some studies suggest that DD genotype may be a risk
      factor for small vessel disease (SVD) stroke. Here, we investigated whether this
      polymorphism is associated with IS of different etiologies in a Polish
      population. SUBJECTS AND METHODS: Ischemic stroke etiology was established
      according to the TOAST criteria. We studied 92 stroke patients with large vessel
      disease and their 184 matched controls; 96 stroke patients with SVD and 192
      controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D
      polymorphism was determined using the polymerase chain reaction method. RESULTS:
      The distribution of ACE genotypes and alleles was essentially the same in all
      analyzed IS subtypes and their matched controls. CONCLUSIONS: We failed to find
      an association between ACE polymorphism and etiological subtypes of IS in a
      Polish population.

PMID- 17022780
TI  - ApoE polymorphism and acute stroke: a study with diffusion- and perfusion
      weighted MRI and MR angiography.
AB  - OBJECTIVES: We examined whether the apolipoprotein E (ApoE) allele epsilon4
      influences imaging findings in stroke as assessed by diffusion- (DWI) and
      perfusion-weighted (PWI) magnetic resonance imaging, and MR angiography (MRA).
      METHODS: Eight ApoE epsilon4 carriers and 15 non-carriers with acute ischemic
      stroke in the anterior circulation underwent DWI, PWI, and MRA within 24 h of
      stroke. DWI and PWI were repeated a week later. The apparent diffusion
      coefficient, relative cerebral volume (rCBV), relative cerebral blood flow (rCBF)
      and relative mean transit time were measured in three subregions on day one.
      RESULTS: In the ischemic core and the area of infarct growth, rCBV values were
      significantly higher in the epsilon4 carriers compared with the non-carriers.
      Based on the MRA findings, collateral blood flow was better in the epsilon4
      carriers than in the non-carriers. Under the comparable severity of
      hypoperfusion, the hypoperfused area proceeded to infarction later or did not
      proceed to infarction at all in the non-carriers. CONCLUSION: These preliminary
      data suggest that in the ApoE allele epsilon4 carriers the threshold for the
      brain tissue to survive hypoperfusion versus to proceed to infarction seems to be
      different from that of the non-carriers.

PMID- 17022781
TI  - Long-term memory following transient global amnesia: an investigation of episodic
      and semantic memory.
AB  - BACKGROUND: Several studies noted persistence of memory impairment following an
      episode of transient global amnesia (TGA) with standard tests. AIM: To specify
      long-term memory impairments in a group of patients selected with stringent
      criteria. METHODS: Both retrograde and anterograde memory were investigated in 32
      patients 13-67 months after a TGA episode with original tasks encompassing
      retrograde semantic memory (academic, public and personal knowledge), retrograde
      episodic memory (autobiographical events) and anterograde episodic memory.
      RESULTS: Patients had preserved academic and public knowledge. Pathological
      scores were obtained in personal verbal fluency for the two most recent periods,
      and patients produced less autobiographical events than controls. However, when
      they were provided time to detail, memories were as episodic as in controls
      regardless of their remoteness. Anterograde episodic tasks revealed a mild but
      significant impairment of the capacity of re-living the condition of encoding,
      i.e. the moment at which words were presented. CONCLUSIONS: Patients who have
      suffered from an episode of TGA manifest deficits of memory focused on the
      retrieval of both recent semantic information and episodic memories and
      especially the capacity of re-living. These deficits may not result from a
      deterioration of memory per se but rather from difficulties in accessing
      memories.

PMID- 17022782
TI  - Hemicrania with massive autonomic manifestations and circumscribed eyelid
      erythema.
AB  - OBJECTIVES: To describe a unilateral headache that in addition to the typical
      shortlasting unilateral neuralgiform headache attacks with conjunctival
      injection, tearing, sweating and rhinorrhea (SUNCT) syndrome - traits with
      excessive and ipsilateral autonomic phenomena - had circumscribed eyelid erythema
      and adjacent ocular redness. OBSERVATIONS: A 60-year-old female had excessive,
      right-sided lacrimation and local pain at 15 years of age. Due to steadily
      increasing discomfort, with lacrimation and swelling over the outer part of the
      upper eyelid, the right lacrimal gland was removed at 20 years of age, with a
      suspicion of lacrimal gland adenoma. Preoperatively, symptomatic side mild-degree
      eyelid erythema/rhinorrhea were integral parts of the attack. After years with
      minor complaints, she, in the mid-twenties, experienced more long-lasting pain
      attacks, and pain soon became the main problem. A marked, distinct erythema on
      the lateral part of the right-sided eyelids and marked, localized 'eye redness'
      in the adjacent area were main ingredients of the attacks together with eyelid
      edema and viscous rhinorrhea. There were visible vessels below the eye, and
      telangiectasia of the upper eyelid. CONCLUSIONS: This headache has many
      similarities with SUNCT - but has several, grossly deviating traits: the temporal
      aspects, excruciatingly intense pain attacks, and above all marked, lateral eye
      lid erythema, and adjacent, massive ocular reddening. This constellation probably
      alienates it from SUNCT.

PMID- 17022783
TI  - Evaluation of neuromuscular transmission by using monopolar needle electrode.
AB  - OBJECTIVE: To evaluate the value of single-fibre electromyography (SFEMG) with
      monopolar electrode (MNPE) in revealing neuromuscular transmission dysfunction.
      MATERIAL AND METHODS: We examined the extensor digitorum communis muscle by using
      single-fibre electrode (SFE) and MNPE sequentially, in randomly assigned 20
      healthy volunteers and in 17 patients with known myasthenia gravis (MG). The high
      pass filter setting was 3 kHz for MNPE. Ten individual jitter values were
      calculated for each electrode in every muscle. Repetitive nerve stimulation (RNS)
      test on trapezius muscle was performed on 15 patients. RESULTS: In controls, the
      mean jitter values were 27 +/- 9 (10-59) micro s with SFE, and 21 +/- 7.2 (9-56)
      micro s with MNPE (P = 0.001). In the MG group, the mean jitter values were 52.4
      +/- 38 (12-221) micro s with SFE, and 51.8 +/- 34.7 (12-179) micro s with MNPE.
      Both electrodes identified junction dysfunction in 14 patients. RNS revealed
      decrement in four patients but 11. CONCLUSION: SFEMG with SFE is still the gold
      standard; however, SFEMG with MNPE is superior to RNS like SFEMG with SFE.

PMID- 17022785
TI  - Novel mitochondrial mutation in the ND4 gene associated with Leigh syndrome.
AB  - We analyzed the complete mitochondrial genome of a 3-month-old female child with
      basal ganglionic lesions and other clinical features suggestive of Leigh
      syndrome, which is caused by variations in mitochondrial and nuclear genes. Our
      study revealed a novel, homoplasmic T11984C missense mutation in ND4 gene, which
      replaces a highly conserved amino acid tyrosine with histidine. Computational
      analysis showed that this mutation alters the secondary structure of ND4 subunit.
      As the mutation observed in this study was novel and homoplasmic, we speculate
      that there could be interplay of this mitochondrial mutation along with nuclear
      gene(s) in the pathogenesis.

PMID- 17022784
TI  - Raised prolactin levels in myasthenia gravis: two case reports and a study of two
      patient populations.
AB  - OBJECTIVES: To describe two patients with myasthenia gravis (MG) and prolactinoma
      and analyze the associations between MG and prolactin (PRL) levels. DESIGN: Two
      case reports and a case-control study of PRL levels in 192 patients with MG.
      PARTICIPANTS: The Immunological Research Laboratory, Center for Molecular
      Medicine, Department of Medicine and the Department of Neurology, Karolinska
      Institutet, Stockholm, Sweden; St Petersburg Medical Academy for Postgraduate
      Studies, and St Petersburg State Medical Pediatric Academy, Russia. RESULTS: Two
      women with MG and thymic hyperplasia accompanied by prolactinomas are described.
      The levels of plasma PRL were raised in 101 women with MG, but not in 91 men.
      There was an association between high PRL levels and high levels of
      autoantibodies against the acetylcholine receptor. CONCLUSIONS: There is an
      association of MG with raised levels of PRL in women. PRL has stimulating effects
      on immune activation and the increased levels might thus be implied in the
      pathophysiology of MG.

PMID- 17022786
TI  - The yield of expanding the therapeutic time window for tPA.
AB  - OBJECTIVES: Intravenous thrombolysis with recombinant tissue plasminogen
      activator (tPA) for acute ischemic stroke has been proved to be effective when
      given within 3 h of onset of stroke symptoms. Partly due to this time limit, less
      than 10% of stroke patients are treated with tPA. This study assessed the
      potential for increased tPA utilization with a theoretical time limit of 6 h.
      MATERIALS AND METHODS: A total of 117 patients admitted with a diagnosis of acute
      cerebrovascular disease were prospectively registered over a 3-month period, with
      emphasis on timing and criteria for tPA treatment. RESULTS: Eighty-eight of 117
      patients (75%) had an acute ischemic stroke. Of these, 23% arrived within 3 h, 8%
      within 3-6 h, and 69% later than 6 h after symptom onset. Of the seven patients
      in the 3-6 h group, only one had time delay as the only contraindication to tPA.
      CONCLUSIONS: This study suggests that reducing patient delay, rather than
      increasing the time limit for thrombolytic treatment, may increase the frequency
      of tPA utilization. Changing time limits for thrombolysis may reduce time delay
      from stroke onset to arrival in hospital due to more rapid handling of patients
      by the emergency medical services.

PMID- 17022787
TI  - TIA associated with over-the-counter cold preparation.

PMID- 17022788
TI  - Depression in Parkinson's disease - a review.

PMID- 17022789
TI  - Positive findings for negative symptoms of schizophrenia: no longer untreatable?

PMID- 17022790
TI  - Prejudice and schizophrenia: a review of the 'mental illness is an illness like
      any other' approach.
AB  - OBJECTIVE: Many anti-stigma programmes use the 'mental illness is an illness like
      any other' approach. This review evaluates the effectiveness of this approach in
      relation to schizophrenia. METHOD: The academic literature was searched, via
      PsycINFO and MEDLINE, to identify peer-reviewed studies addressing whether public
      espousal of a biogenetic paradigm has increased over time, and whether biogenetic
      causal beliefs and diagnostic labelling are associated with less negative
      attitudes. RESULTS: The public, internationally, continues to prefer psychosocial
      to biogenetic explanations and treatments for schizophrenia. Biogenetic causal
      theories and diagnostic labelling as 'illness', are both positively related to
      perceptions of dangerousness and unpredictability, and to fear and desire for
      social distance. CONCLUSION: An evidence-based approach to reducing
      discrimination would seek a range of alternatives to the 'mental illness is an
      illness like any other' approach, based on enhanced understanding, from multi
      disciplinary research, of the causes of prejudice.

PMID- 17022791
TI  - The treatment of negative symptoms and deficit states of chronic schizophrenia:
      olanzapine compared to amisulpride and placebo in a 6-month double-blind
      controlled clinical trial.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy of olanzapine (5 and
      20 mg/day) over a 6-month period in chronic schizophrenic patients experiencing
      predominantly negative symptoms. METHOD: Two hundred and forty-four patients
      participated in a 6-month multicenter double-blind trial of placebo (n = 34),
      olanzapine 5 mg/day (n = 70), olanzapine 20 mg/day (n = 70), or amisulpride 150
      mg/day (n = 70). Primary measure was the scale for the assessment of negative
      symptoms. RESULTS: Olanzapine 5 mg/day showed significantly greater improvement
      than placebo in negative symptoms and in the Positive and Negative Syndrome Scale
      total score. Baseline positive symptoms were low at baseline and changed
      minimally. The neurological tolerance of olanzapine, amisulpride and placebo were
      comparable. CONCLUSION: Olanzapine 5 mg/day was effective in treating negative
      symptoms in a group of schizophrenic with predominantly negative symptoms during
      the stabilization phase. Improvement in positive symptoms or extrapyramidal
      symptoms (EPS) was unlikely to explain this result while improvement in
      depression may have partially contributed.

PMID- 17022792
TI  - Two years of continued early treatment for recent-onset schizophrenia: a
      randomised controlled study.
AB  - OBJECTIVE: This random-controlled study evaluated benefits derived from continued
      integrated biomedical and psychosocial treatment for recent-onset schizophrenia.
      METHOD: Fifty cases of schizophrenia of less than 2 years duration were allocated
      randomly to integrated or standard treatment (ST) for 2 years. ST comprised
      optimal pharmacotherapy and case management, while IT also included cognitive
      behavioural family treatment, that incorporated skills training, cognitive
      behavioural strategies for residual psychotic and non-psychotic problems and home
      based crisis management. Psychopathology, functioning, hospitalisation and
      suicidal behaviours were assessed two monthly and a composite index, reflecting
      overall clinical outcome was derived. RESULTS: IC proved superior to ST in
      reducing negative symptoms, minor psychotic episodes and in stabilising positive
      symptoms, but did not reduce hospital admissions or major psychotic recurrences.
      The composite index showed that significantly more IC patients (53%) had
      excellent 2-year outcomes than ST (25%). CONCLUSION: Evidence-based treatment
      achieves greater clinical benefits than pharmacotherapy and case management alone
      for recent-onset schizophrenia.

PMID- 17022793
TI  - Treated incidence of first-episode psychosis in the catchment area of EPPIC
      between 1997 and 2000.
AB  - OBJECTIVE: To identify the treated incidence of psychosis in catchment of the
      Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia.
      METHOD: Cases were aged 15-29 years with a first episode of a psychotic disorder
      accepted into EPPIC between 1997 and 2000. Age- and sex-specific incidence rates
      per 10,000 person-years were calculated in 5 year age bands. Rate ratios were
      used for age group comparisons. RESULTS: The age-specific treated incidence of
      first-episode psychosis in 15-29-year old individuals was 16.7 per 10,000 person
      years in males, and 8.1 per 10,000 person-years in females. The incidence was
      highest in 20-24-year-old males and in 15-19-year-old females. For both sexes,
      incidence rates were significantly lower in the 25-29-year age group.
      CONCLUSIONS: The incidence of psychosis in the catchment of EPPIC was higher than
      previously reported, especially in female teenagers. Peak rates in 15-24 year
      olds suggest a youth model approach to early psychosis may be indicated.

PMID- 17022794
TI  - MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in
      antipsychotic-naive schizophrenia.
AB  - OBJECTIVE: To examine the volumetric and metabolic correlates of caudate nucleus
      in antipsychotic-naive schizophrenia patients in comparison with healthy
      controls. METHOD: Twelve antipsychotic-naive schizophrenia patients and 13
      healthy controls underwent (31)P magnetic resonance spectroscopy of basal
      ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using
      scion image software. RESULTS: Patients had significantly smaller caudate volume
      than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total
      adenosine tri-phosphate ratios of both caudate nuclei were significantly lower in
      patients than controls. Significant negative correlation was found between the
      left caudate volume and left PCr/total phosphorus ratio in the patients. Age at
      onset of psychosis had i) significant negative correlation with right and left
      caudate volumes and ii) significant positive correlation with left PCr/total
      phosphorus ratio. CONCLUSION: The metabolic and volumetric abnormalities of
      caudate nucleus in antipsychotic-naive schizophrenia patients support
      neurodevelopmental etiopathogenesis.

PMID- 17022795
TI  - Cerebellar and other neurological soft signs in antipsychotic-naive
      schizophrenia.
AB  - OBJECTIVE: Cerebellar neurological abnormalities in schizophrenia have been
      associated with severe negative symptoms, cognitive deficits, and smaller
      cerebellar volume. This study assessed the comparative discriminant validity
      between Cerebellar Soft Signs (CSS) vs. other neurological soft signs (ONSS) [in
      discriminating between schizophrenia patients and healthy controls] as well as
      the relationship between the soft signs and psychopathology. METHOD:
      Antipsychotic-naive schizophrenia patients (n = 32) and healthy subjects (n = 32)
      were examined using International Co-Operative Ataxia Rating Scale and
      Neurological Evaluation Scale. RESULTS: Mean CSS scores, ONSS total score, and
      Sensory Integration Signs sub-score were significantly higher in patients.
      Discriminant analysis revealed two CSS sub-scores (but none of the ONSS scores)
      to be significant (P < 0.0001) accounting for 78% of classification. CSS total
      score, Posture sub-score, and Oculomotor sub-score had significant positive
      correlation with negative syndrome score. CONCLUSION: Findings support intrinsic
      cerebellar dysfunction in schizophrenia. The observations are discussed in
      relationship with cognitive dysmetria.

PMID- 17022796
TI  - Good school performance is a risk factor of suicide in psychoses: a 35-year
      follow up of the Northern Finland 1966 Birth Cohort.
AB  - OBJECTIVE: Our aim was to analyse the relationship between good school
      performance and risk of suicide in the Northern Finland 1966 Birth Cohort,
      especially in psychoses. METHOD: A total of 11,017 cohort members who were alive
      at the age of 16 years were followed up to the age of 35 years. School
      performance was measured by the school marks given at age 16 at the end of
      comprehensive school. School, diagnostic and mortality data were based on
      national registers. RESULTS: For psychotic persons having good school performance
      (highest 20%), the adjusted hazard ratio (HR) for suicide was 3.56 (0.97-13.05)
      compared with the remaining 80%. In the non-psychotic population (97% without
      psychiatric hospitalization), accordingly, adjusted HR was 0.28 (0.07-1.16).
      Interaction (school performance x psychiatric diagnosis) was significant (P =
      0.01) even when adjusted with gender, social class and age of onset of illness.
      CONCLUSION: Good school performance at age 16 years is associated with increased
      risk of suicide (before age 35 years) in persons who develop psychosis, whereas
      in persons who do not develop psychosis, it is associated with lower suicide
      risk.

PMID- 17022797
TI  - The impact of caregivers' characteristics, patients' conditions and regional
      differences on family burden in schizophrenia: a longitudinal analysis.
AB  - OBJECTIVE: Impact of caregiver characteristics, patient variables, and regional
      differences on family burden. METHOD: Two hundred and eighteen schizophrenia
      patients and key-relatives of an urban and a rural area were examined five times
      over 30 months. Patients' psychopathology, service utilization; relatives'
      burden, coping abilities and contact duration with the patients were recorded.
      Effects of interpersonal differences and intrapersonal changes over time were
      analyzed with regression models. RESULTS: Interpersonal differences (patients'
      positive and negative symptoms, relatives' coping abilities, and patient contact)
      and intrapersonal changes (relatives' coping abilities, patients' negative
      symptoms and utilization of community care) predicted family burden. CONCLUSION:
      Family education programs should help caregivers to improve their coping
      strategies. Therapy solutions must address negative symptoms just as much as
      positive symptoms, as these especially impact caregivers. Intensified community
      based care can reduce burden, but provision alone is not sufficient.
      Psychiatrists and caregivers should motivate patients to take advantage of such
      offers.

PMID- 17022798
TI  - Frontal lobe syndrome or adolescent-onset schizophrenia? A case report.
AB  - OBJECTIVE: To highlight the difficulties that abound in making a clinical
      distinction between early-onset schizophrenia (EOS) and juvenile frontal dementia
      early in the course of illness. METHOD: Clinical information and data from
      investigations in single case was collated and reviewed. RESULTS: A 15-year-old
      girl was admitted to our psychiatric unit because of cognitive decline and formal
      thought disorder with echopraxia, echolalia and palilalia, and a lack of
      flexibility in the use of cognitive and motor strategies that culminated in
      psychosis. A single photon emission computerized tomography scan showed marked
      frontal lobe hypoperfusion; however, on proton spectroscopy there was no
      differential in N-acetyl aspartate levels. CONCLUSION: Hypofrontality in EOS is
      well established and the association of frontal functional alterations,
      neuropsychological impairment and psychotic symptomatology is suggestive of
      frontal lobe prodrome that precedes the onset of psychosis.

PMID- 17022803
TI  - The BiSearch web server.
AB  - BACKGROUND: A large number of PCR primer-design softwares are available online.
      However, only very few of them can be used for the design of primers to amplify
      bisulfite-treated DNA templates, necessary to determine genomic DNA methylation
      profiles. Indeed, the number of studies on bisulfite-treated templates
      exponentially increases as determining DNA methylation becomes more important in
      the diagnosis of cancers. Bisulfite-treated DNA is difficult to amplify since
      undesired PCR products are often amplified due to the increased sequence
      redundancy after the chemical conversion. In order to increase the efficiency of
      PCR primer-design, we have developed BiSearch web server, an online primer-design
      tool for both bisulfite-treated and native DNA templates. RESULTS: The web tool
      is composed of a primer-design and an electronic PCR (ePCR) algorithm. The
      completely reformulated ePCR module detects potential mispriming sites as well as
      undesired PCR products on both cDNA and native or bisulfite-treated genomic DNA
      libraries. Due to the new algorithm of the current version, the ePCR module
      became approximately hundred times faster than the previous one and gave the best
      performance when compared to other web based tools. This high-speed ePCR analysis
      made possible the development of the new option of high-throughput primer
      screening. BiSearch web server can be used for academic researchers at the
      http://bisearch.enzim.hu site. CONCLUSION: BiSearch web server is a useful tool
      for primer-design for any DNA template and especially for bisulfite-treated
      genomes. The ePCR tool for fast detection of mispriming sites and alternative PCR
      products in cDNA libraries and native or bisulfite-treated genomes are the unique
      features of the new version of BiSearch software.

PMID- 17022804
TI  - Comparative proteomic analysis of high cell density cultivations with two
      recombinant Bacillus megaterium strains for the production of a heterologous
      dextransucrase.
AB  - High cell density cultivations were performed under identical conditions for two
      Bacillus megaterium strains (MS941 and WH320), both carrying a heterologous
      dextransucrase (dsrS) gene under the control of the xylA promoter. At
      characteristic points of the cultivations (end of batch, initial feeding, before
      and after induction) the proteome was analyzed based on two dimensional gel
      electrophoresis and mass spectrometric protein identification using the protein
      database "bmegMEC.v2" recently made available. High expression but no secretion
      of DsrS was found for the chemical mutant WH320 whereas for MS 941, a defined
      protease deficient mutant of the same parent strain (DSM319), not even expression
      of DsrS could be detected. The proteomic analysis resulted in the identification
      of proteins involved in different cellular pathways such as in central carbon and
      overflow metabolism, in protein synthesis, protein secretion and degradation, in
      cell wall metabolism, in cell division and sporulation, in membrane transport and
      in stress responses. The two strains exhibited considerable variations in
      expression levels of specific proteins during the different phases of the
      cultivation process, whereas induction of DsrS production had, in general, little
      effect. The largely differing behaviour of the two strains with regard to DsrS
      expression can be attributed, at least in part, to changes observed in the
      proteome which predominantly concern biosynthetic enzymes and proteins belonging
      to the membrane translocation system, which were strongly down-regulated at high
      cell densities in MS941 compared with WH320. At the same time a cell envelope
      associated quality control protease and two peptidoglycan-binding proteins
      related to cell wall turnover were strongly expressed in MS941 but not found in
      WH320. However, to further explain the very different physiological responses of
      the two strains to the same cultivation conditions, it is necessary to identify
      the mutated genes in WH320 in addition to the known lacZ. In view of the results
      of this proteomic study it seems that at high cell density conditions and hence
      low growth rates MS941, in contrast to WH320, does not maintain a vegetative
      growth which is essential for the expression of the foreign dsrS gene by using
      the xylA promoter. It is conceivable that applications of a promoter which is
      highly active under nutrient-limited cultivation conditions is necessary, at
      least for MS941, for the overexpression of recombinant genes in such B.
      megaterium fed-batch cultivation process. However to obtain a heterologous
      protein in secreted and properly folded form stills remains a big challenge.

PMID- 17022805
TI  - Epidemiology and clinical outcome of virus-positive respiratory samples in
      ventilated patients: a prospective cohort study.
AB  - INTRODUCTION: Respiratory viruses are a major cause of respiratory tract
      infections. The prevalence of a virus-positive respiratory sample and its
      significance in patients requiring mechanical ventilation remain unknown.
      METHODS: We conducted a cohort study in all consecutive adults ventilated for
      more than 48 hours admitted to a 22-bed medical intensive care unit during a 12
      month period. Respiratory samples at the time of intubation were assessed by
      culture, by indirect immunofluorescence assay or by molecular methods in
      systematic tracheobronchial aspirates. Patients with a virus-negative respiratory
      sample at the time of intubation were considered unexposed and served as the
      control group. RESULTS: Forty-five viruses were isolated in 41/187 (22%)
      patients. Rhinovirus was the most commonly isolated virus (42%), followed by
      herpes simplex virus type 1 (22%) and virus influenza A (16%). In multivariate
      analysis controlling for the Acute Pathophysiology and Chronic Health Evaluation
      II score, patients with respiratory disorder at admission (adjusted odds ratio,
      2.1; 95% confidence interval, 0.8-5.1; P = 0.12), with chronic obstructive
      pulmonary disease/asthma patients (adjusted odds ratio, 3.0; 95% confidence
      interval, 1.3-6.7; P = 0.01) and with admission between 21 November and 21 March
      (adjusted odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P = 0.008) were
      independently associated with a virus-positive sample. Among the 122 patients
      admitted with respiratory disorder, a tracheobronchial aspirate positive for
      respiratory viruses at the time of intubation (adjusted hazard ratio, 0.273; 95%
      confidence interval, 0.096-0.777; P < 0.006) was independently associated with
      better survival, controlling for the Simplified Acute Physiology Score II and
      admission for cardiogenic shock or cardiac arrest. Among the remaining 65
      patients, a virus-positive sample on intubation did not predict survival.
      CONCLUSION: We confirmed the pathogenic role of respiratory viruses in the
      intensive care unit, particularly rhinovirus. We suggest, however, that the
      prognostic value of virus-associated respiratory disorder is better than that of
      other causes of respiratory disorder.

PMID- 17022806
TI  - Activation of chloride transport in CF airway epithelial cell lines and primary
      CF nasal epithelial cells by S-nitrosoglutathione.
AB  - BACKGROUND: It has been suggested that low microM concentrations of S
      nitrosoglutathione (GSNO), an endogenous bronchodilator, may promote maturation
      of the defective cystic fibrosis (CF) transmembrane conductance regulator (CFTR).
      Because nitric oxide (NO) and GSNO levels appear to be low in the CF airway,
      there is an interest in the possibility that GSNO replacement could be of
      therapeutic benefit in CF. METHODS: The effect of GSNO on chloride (Cl-)
      transport was investigated in primary nasal epithelial cells obtained from CF
      patients homozygous for the delF508 mutation, as well as in two CF cell lines
      (CFBE and CFSME), using both a fluorescent Cl- indicator and X-ray microanalysis.
      Maturation of delF508 CFTR was determined by immunoblotting. RESULTS: Treatment
      with 60 microM GSNO for 4 hours increased cAMP-induced chloride efflux in nasal
      epithelial cells from 18 out of 21 CF patients, but did not significantly affect
      Cl- efflux in cells from healthy controls. This Cl- efflux was confirmed by
      measurements with a fluorescent Cl- indicator in the CFBE and CFSME cell lines.
      The effect of GSNO on Cl- efflux in CFBE cells could be inhibited both by a
      specific thiazolidinone CFTR inhibitor (CFTRinh-172) and by 4,4'
      diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (H2DIDS). X-ray
      microanalysis showed that, following 4 hours incubation with 60 microM GSNO, cAMP
      agonists caused a decrease in the cellular Cl- concentration in CFBE cells,
      corresponding to Cl- efflux. GSNO exposure resulted in an increase in the protein
      expression and maturation, as shown by immunoblot analysis. GSNO did not increase
      the cytosolic Ca2+ concentration in cultured airway epithelial cells. CONCLUSION:
      Previous studies have suggested that treatment with GSNO promotes maturation of
      delF508-CFTR, consistent with our results in this study. Here we show that GSNO
      increases chloride efflux, both in the two CF cell lines and in primary nasal
      epithelial cells from delF508-CF patients. This effect is at least in part
      mediated by CFTR. GSNO may be a candidate for pharmacological treatment of the
      defective chloride transport in CF epithelial cells.

PMID- 17022807
TI  - The role of diagnostic VATS in penetrating thoracic injuries.
AB  - BACKGROUND: Penetrating chest injuries account for 1-13% of thoracic trauma
      hospital admissions and most of these are managed with a conservative approach.
      Nevertheless, 18-30% of cases managed only with tube thoracostomy have residual
      clotted blood, considered the major risk factor for the development of
      fibrothorax and empyema. In addition, 4-23% of chest injury patients present
      persistent pneumothorax and 15-59% present an injury to the diaphragm, which is
      missed in 30% of cases. In order to make a correct diagnosis, reduce the number
      of missed injuries, chronic sequelae and late mortality we propose performing
      surgical exploration of all patients with a penetrating injury of the pleural
      cavity. METHODS: 1270 patients who sustained thoracic trauma were admitted to our
      hospital between 1994 and 2004. Of these, 16 patients had penetrating injuries:
      thirteen were surgically explored by means of Video Assisted Thoracic Surgery
      (VATS), and 3 with thoracotomy due to hemodynamic instability or suspected lesion
      of the heart or great vessels. RESULTS: In the 13 patients who underwent VATS, 5
      injuries to the diaphragm, 3 lesions to an intercostal artery, and 1 lesion to
      the diaphragmatic artery were detected. In 12 of these patients a laceration of
      the pulmonary parenchyma was also present. A conversion to thoracotomy was
      necessary due to a broad laceration of the diaphragm and due to hemostasis of an
      intercostal artery. In all but one case, which was later converted, diagnostic
      imaging missed the diagnosis of laceration of the diaphragm. There was no intra-
      or postoperative mortality, and average hospital stay was five days. CONCLUSION:
      VATS is a safe and effective way to diagnose and manage penetrating thoracic
      injuries, and its extensive use leads to a reduction in the number of missed,
      potentially fatal lesions as well as in chronic sequelae.

PMID- 17022808
TI  - Feature selection using Haar wavelet power spectrum.
AB  - BACKGROUND: Feature selection is an approach to overcome the 'curse of
      dimensionality' in complex researches like disease classification using
      microarrays. Statistical methods are utilized more in this domain. Most of them
      do not fit for a wide range of datasets. The transform oriented signal processing
      domains are not probed much when other fields like image and video processing
      utilize them well. Wavelets, one of such techniques, have the potential to be
      utilized in feature selection method. The aim of this paper is to assess the
      capability of Haar wavelet power spectrum in the problem of clustering and gene
      selection based on expression data in the context of disease classification and
      to propose a method based on Haar wavelet power spectrum. RESULTS: Haar wavelet
      power spectra of genes were analysed and it was observed to be different in
      different diagnostic categories. This difference in trend and magnitude of the
      spectrum may be utilized in gene selection. Most of the genes selected by earlier
      complex methods were selected by the very simple present method. Each earlier
      works proved only few genes are quite enough to approach the classification
      problem 1. Hence the present method may be tried in conjunction with other
      classification methods. The technique was applied without removing the noise in
      data to validate the robustness of the method against the noise or outliers in
      the data. No special software or complex implementation is needed. The qualities
      of the genes selected by the present method were analysed through their gene
      expression data. Most of them were observed to be related to solve the
      classification issue since they were dominant in the diagnostic category of the
      dataset for which they were selected as features. CONCLUSION: In the present
      paper, the problem of feature selection of microarray gene expression data was
      considered. We analyzed the wavelet power spectrum of genes and proposed a
      clustering and feature selection method useful for classification based on Haar
      wavelet power spectrum. Application of this technique in this area is novel,
      simple, and faster than other methods, fit for a wide range of data types. The
      results are encouraging and throw light into the possibility of using this
      technique for problem domains like disease classification, gene network
      identification and personalized drug design.

PMID- 17022809
TI  - M-GCAT: interactively and efficiently constructing large-scale multiple genome
      comparison frameworks in closely related species.
AB  - BACKGROUND: Due to recent advances in whole genome shotgun sequencing and
      assembly technologies, the financial cost of decoding an organism's DNA has been
      drastically reduced, resulting in a recent explosion of genomic sequencing
      projects. This increase in related genomic data will allow for in depth studies
      of evolution in closely related species through multiple whole genome
      comparisons. RESULTS: To facilitate such comparisons, we present an interactive
      multiple genome comparison and alignment tool, M-GCAT, that can efficiently
      construct multiple genome comparison frameworks in closely related species. M
      GCAT is able to compare and identify highly conserved regions in up to 20 closely
      related bacterial species in minutes on a standard computer, and as many as 90
      (containing 75 cloned genomes from a set of 15 published enterobacterial genomes)
      in an hour. M-GCAT also incorporates a novel comparative genomics data
      visualization interface allowing the user to globally and locally examine and
      inspect the conserved regions and gene annotations. CONCLUSION: M-GCAT is an
      interactive comparative genomics tool well suited for quickly generating multiple
      genome comparisons frameworks and alignments among closely related species. M
      GCAT is freely available for download for academic and non-commercial use at:
      http://alggen.lsi.upc.es/recerca/align/mgcat/intro-mgcat.html.

PMID- 17022810
TI  - Overexpression of Eag1 potassium channels in clinical tumours.
AB  - BACKGROUND: Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1)
      are associated with the production of tumours in patients and in animals. We have
      now studied the expression pattern of the Eag1 channel in a large range of normal
      and tumour tissues from different collections utilising molecular biological and
      immunohistochemical techniques. RESULTS: The use of reverse transcription real
      time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that
      expression of the channel is normally limited to specific areas of the brain and
      to restricted cell populations throughout the body. Tumour samples, however,
      showed a significant overexpression of the channel with high frequency (up to 80%
      depending on the tissue source) regardless of the detection method (staining with
      either one of the antibodies, or detection of Eag1 RNA). CONCLUSION: Inhibition
      of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may
      therefore represent a promising target for the tailored treatment of human
      tumours. Furthermore, as normal cells expressing Eag1 are either protected by the
      blood-brain barrier or represent the terminal stage of normal differentiation,
      Eag1 based therapies could produce only minor side effects.

PMID- 17022811
TI  - Ether a go-go potassium channel expression in soft tissue sarcoma patients.
AB  - BACKGROUND: The expression of the human Eag1 potassium channel (Kv10.1) is
      normally restricted to the adult brain, but it has been detected in both tumour
      cell lines and primary tumours. Our purpose was to determine the frequency of
      expression of Eag1 in soft tissue sarcoma and its potential clinical
      implications. RESULTS: We used specific monoclonal antibodies to determine the
      expression levels of Eag1 in soft tissue sarcomas from 210 patients by
      immunohistochemistry. Eag1 was expressed in 71% of all tumours, with frequencies
      ranging from 56% (liposarcoma) to 82% (rhabdomyosarcoma). We detected differences
      in expression levels depending on the histological type, but no association was
      seen between expression of this protein and sex, age, grade or tumour size. Four
      cell lines derived from relevant sarcoma histological types (fibrosarcoma and
      rhabdomyosarcoma) were tested for Eag1 expression by real-time RT-PCR. We found
      all four lines to be positive for Eag1. In these cell lines, blockage of Eag1 by
      RNA interference led to a decrease in proliferation. CONCLUSION: Eag1 is
      aberrantly expressed in over 70% sarcomas. In sarcoma cell lines, inhibition of
      Eag1 expression and/or function leads to reduced proliferation. The high
      frequency of expression of Eag1 in primary tumours and the restriction of normal
      expression of the channel to the brain, suggests the application of this protein
      for diagnostic or therapeutic purposes.

PMID- 17022812
TI  - Limited proteolysis of human histone deacetylase 1.
AB  - BACKGROUND: Histone deacetylase (HDAC) proteins are associated with cell
      proliferation, differentiation, apoptosis, and cancer. Specifically, HDAC1 is
      linked with cell growth, a hallmark of cancer formation. HDAC1 is a
      phosphoprotein and phosphorylation at S421 and S423 promotes HDAC1 enzymatic
      activity and protein association. While single and double point mutants of HDAC1
      at S421 and S423 appear functionally similar, the evidence suggests that HDAC1 is
      phosphorylated simultaneously at both S421 and S423 in vivo. Additional
      experiments are necessary to probe the role of double phosphorylation of HDAC1 at
      S421 and S423. RESULTS: To characterize HDAC1 phosphorylation at S421 and S423,
      limited proteolysis of HDAC1 was performed for the first time. HDAC1 degraded
      without production of discrete fragments. By performing concentration-dependent
      proteolysis, HDAC1 double point mutants with disrupted phosphorylation at S421
      and S423 displayed different trypsin sensitivities compared to wild type HDAC1.
      Unexpectedly, HDAC1 single point mutants with disrupted phosphorylation at either
      S421 or S423 demonstrated protease sensitivity similar to the wild type HDAC1.
      CONCLUSION: Concentration-dependent proteolysis experiments provide evidence that
      phosphorylation of S421 and S423 individually contribute to HDAC1 function. In
      addition, the limited proteolysis experiments support a model where associated
      proteins promote HDAC1 enzymatic activity, reinforcing the importance of protein
      interactions in HDAC1 structure and function. Finally, because HDAC1 does not
      display distinct regions of protease sensitivity, the proteolysis studies suggest
      that HDAC1 comprises inter-related structural regions.

PMID- 17022813
TI  - Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of
      patients with psoriatic arthritis after therapy with anti-TNF-alpha.
AB  - BACKGROUND: Inflammation represents an early and key event in the development of
      both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences
      indicate that the production of TNF-alpha plays a central role in psoriasis by
      sustaining the inflammatory process in the skin as well as in the joints. Among
      the multiple effects produced by TNF-alpha on keratinocytes, the induction of
      matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint
      inflammatory arthritis which acts as an angiogenesis promoting factor, might
      represent a key mechanism in the pathogenesis of the disease. Aims of the present
      study were to investigate a) the role of MMP-9 in the development of psoriasis by
      assessing the presence of MMP-9 in lesional skin and in sera of psoriatic
      patients; b) the association of MMP-9 with the activity of the disease; c) the
      relationship between MMP-9 and TNF-alpha production. METHODS: Eleven psoriatic
      patients, clinically presenting joint symptoms associated to the cutaneous
      disease, were included in a therapeutic protocol based on the administration of
      anti-TNF-alpha monoclonal antibody (Infliximab). Sera and skin biopsies were
      collected before treatment and after 6 weeks of therapy. Tissues were kept in
      short term cultures and production soluble mediators such as TNF-alpha, MMP-9,
      MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the
      development of plaque psoriasis, were measured in the culture supernatants by
      immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations
      were also measured in the sera. The cutaneous activity of disease was evaluated
      by the Psoriasis Area and Severity Index (PASI). RESULTS: Clinical and laboratory
      assessment indicated that all but one patients had a significant improvement of
      the PASI score after three months of therapy. The clinical amelioration was
      associated to a significant decrease of MMP-9 (P = 0.017), TNF-alpha (P = 0.005)
      and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies
      before and after therapy. In addition, significant correlations were found
      between the PASI measurements and TNF-alpha (r2 = 0.33, P = 0.005), MMP-9 (r2 =
      0.25, P = 0.017), E-selectin (r2 = 0.24, P = 0.018) production. MMP-9 levels were
      significantly correlated with those of TNF-alpha (r2 = 0.30, P = 0.008). A
      significant decrease of MMP-9 in the sera, associated to the clinical improvement
      was also found. CONCLUSION: Our findings show the existence of a direct
      relationship between MMP-9 and TNF-alpha production strongly suggesting that MMP
      9 may play a key role in the skin inflammatory process in psoriasis.

PMID- 17022814
TI  - The use of the SF-36 questionnaire in adult survivors of childhood cancer:
      evaluation of data quality, score reliability, and scaling assumptions.
AB  - BACKGROUND: The SF-36 has been used in a number of previous studies that have
      investigated the health status of childhood cancer survivors, but it never has
      been evaluated regarding data quality, scaling assumptions, and reliability in
      this population. As health status among childhood cancer survivors is being
      increasingly investigated, it is important that the measurement instruments are
      reliable, validated and appropriate for use in this population. The aim of this
      paper was to determine whether the SF-36 questionnaire is a valid and reliable
      instrument in assessing self-perceived health status of adult survivors of
      childhood cancer. METHODS: We examined the SF-36 to see how it performed with
      respect to (1) data completeness, (2) distribution of the scale scores, (3) item
      internal consistency, (4) item-discriminant validity, (5) internal consistency,
      and (6) scaling assumptions. For this investigation we used SF-36 data from a
      population-based study of 10,189 adult survivors of childhood cancer. RESULTS:
      Overall, missing values ranged per item from 0.5 to 2.9 percent. Ceiling effects
      were found to be highest in the role limitation-physical (76.7%) and role
      limitation-emotional (76.5%) scales. All correlations between items and their
      hypothesised scales exceeded the suggested standard of 0.40 for satisfactory item
      consistency. Across all scales, the Cronbach's alpha coefficient of reliability
      was found to be higher than the suggested value of 0.70. Consistent across all
      cancer groups, the physical health related scale scores correlated strongly with
      the Physical Component Summary (PCS) scale scores and weakly with the Mental
      Component Summary (MCS) scale scores. Also, the mental health and role limitation
      emotional scales correlated strongly with the MCS scale score and weakly with the
      PCS scale score. Moderate to strong correlations with both summary scores were
      found for the general health perception, energy/vitality, and social functioning
      scales. CONCLUSION: The findings presented in this paper provide support for the
      validity and reliability of the SF-36 when used in long-term survivors of
      childhood cancer. These findings should encourage other researchers and health
      care practitioners to use the SF-36 when assessing health status in this
      population, although it should be recognised that ceiling effects can occur.

PMID- 17022815
TI  - Economic evaluation of the artificial liver support system MARS in patients with
      acute-on-chronic liver failure.
AB  - BACKGROUND: Acute-on-chronic liver failure (ACLF) is a life threatening acute
      decompensation of a pre-existing chronic liver disease. The artificial liver
      support system MARS is a new emerging therapeutic option possible to be
      implemented in routine care of these patients. The medical efficacy of MARS has
      been demonstrated in first clinical studies, but economic aspects have so far not
      been investigated. Objective of this study was to estimate the cost-effectiveness
      of MARS. METHODS: In a clinical cohort trial with a prospective follow-up of 3
      years 33 ACLF-patients treated with MARS were compared to 46 controls. Survival,
      health-related quality of life as well as direct medical costs for in- and
      outpatient treatment from a health care system perspective were determined. Based
      on the differences in outcome and indirect costs the cost-effectiveness of MARS
      expressed as incremental costs per life year gained and incremental costs per
      QALY gained was estimated. RESULTS: The average initial intervention costs for
      MARS were 14600 EUR per patient treated. Direct medical costs over 3 years follow
      up were overall 40000 EUR per patient treated with MARS respectively 12700 EUR in
      controls. The 3 year survival rate after MARS was 52% compared to 17% in
      controls. Kaplan-Meier analysis of cumulated survival probability showed a highly
      significant difference in favour of MARS. Incremental costs per life-year gained
      were 31400 EUR; incremental costs per QALY gained were 47200 EUR. CONCLUSION: The
      results after 3 years follow-up of the first economic evaluation study of MARS
      based on empirical patient data are presented. Although high initial treatment
      costs for MARS occur the significantly better survival seen in this study led to
      reasonable costs per live year gained. Further randomized controlled trials
      investigating the medical efficacy and the cost-effectiveness are recommended.

PMID- 17022816
TI  - New patient-oriented summary measure of net total gain in certainty for
      dichotomous diagnostic tests.
AB  - OBJECTIVES: To introduce a new, patient-oriented predictive index as a measure of
      gain in certainty. STUDY DESIGN: Algebraic equations. RESULTS: A new measure is
      suggested based on error rates in a patient population. The new Predictive
      Summary Index (PSI) reflects the true total gain in certainty obtained by
      performing a diagnostic test based on knowledge of disease prevalence, i.e., the
      overall additional certainty. We show that the overall gain in certainty can be
      expressed in the form of the following expression: PSI = PPV+NPV-1. PSI is a more
      comprehensive measure than the post-test probability or the Youden Index (J). The
      reciprocal of J is interpreted as the number of persons with a given disease who
      need to be examined in order to detect correctly one person with the disease. The
      reciprocal of PSI is suggested as the number of persons who need to be examined
      in order to correctly predict a diagnosis of the disease. CONCLUSION: PSI
      provides more information than J and the predictive values, making it more
      appropriate in a clinical setting.

PMID- 17022817
TI  - Establishment of endolithic populations of extremophilic Cyanidiales
      (Rhodophyta).
AB  - BACKGROUND: Cyanidiales are unicellular extremophilic red algae that inhabit
      acidic and high temperature sites around hot springs and have also adapted to
      life in endolithic and interlithic habitats. Comparative genomic analysis of
      Cyanidioschyzon merolae and Galdieria sulphuraria predicts that the latter may be
      more broadly distributed in extreme environments because its genome contains
      membrane transporters involved in the uptake of reduced carbon compounds that are
      absent from C. merolae. Analysis of an endolithic site in the Phlegrean Fields
      near Naples, Italy is consistent with this prediction showing this population to
      be comprised solely of the newly described lineage Galdieria-B and C. merolae to
      be limited to humid habitats. Here, we conducted an environmental PCR survey of
      another extreme environment in Tuscany, Italy and contrasted Cyanidiales
      population structure at endolithic and interlithic habitats in Naples and
      Tuscany. RESULTS: We find a second Galdieria lineage (Galdieria-A) in endolithic
      and interlithic habitats in Tuscany but surprisingly Cyanidium was also present
      at these sites. The photoautotrophic Cyanidium apparently survives below the rock
      surface where sufficient light is available for photosynthesis. C. merolae is
      absent from all endolithic and interlithic sites in Tuscany. Population genetic
      analyses of a partial calmodulin gene fragment suggest a recent establishment or
      recurrent gene flow between populations in Tuscany, whereas the highly structured
      Galdieria-B population in Naples likely originated from 2-3 founder events. We
      find evidence of several recombination events across the calmodulin gene,
      potentially indicating the presence of sexual reproduction in the Tuscany
      populations. CONCLUSION: Our study provides important data regarding population
      structure in extreme endolithic environments and insights into how Cyanidiales
      may be established in and adapt to these hostile environments.

PMID- 17022818
TI  - Selecting patients for randomized trials: a systematic approach based on risk
      group.
AB  - BACKGROUND: A key aspect of randomized trial design is the choice of risk group.
      Some trials include patients from the entire at-risk population, others accrue
      only patients deemed to be at increased risk. We present a simple statistical
      approach for choosing between these approaches. The method is easily adapted to
      determine which of several competing definitions of high risk is optimal. METHOD:
      We treat eligibility criteria for a trial, such as a smoking history, as a
      prediction rule associated with a certain sensitivity (the number of patients who
      have the event and who are classified as high risk divided by the total number
      patients who have an event) and specificity (the number of patients who do not
      have an event and who do not meet criteria for high risk divided by the total
      number of patients who do not have an event). We then derive simple formulae to
      determine the proportion of patients receiving intervention, and the proportion
      who experience an event, where either all patients or only those at high risk are
      treated. We assume that the relative risk associated with intervention is the
      same over all choices of risk group. The proportion of events and interventions
      are combined using a net benefit approach and net benefit compared between
      strategies. RESULTS: We applied our method to design a trial of adjuvant therapy
      after prostatectomy. We were able to demonstrate that treating a high risk group
      was superior to treating all patients; choose the optimal definition of high
      risk; test the robustness of our results by sensitivity analysis. Our results had
      a ready clinical interpretation that could immediately aid trial design.
      CONCLUSION: The choice of risk group in randomized trials is usually based on
      rather informal methods. Our simple method demonstrates that this decision can be
      informed by simple statistical analyses.

PMID- 17022819
TI  - Explanations of socioeconomic differences in changes in physical function in
      older adults: results from the Longitudinal Aging Study Amsterdam.
AB  - BACKGROUND: This study examines the association between socioeconomic status and
      changes in physical function in younger- (aged 55-70 years) and older-old (aged
      70-85 years) adults and seeks to determine the relative contribution of diseases,
      behavioral, and psychosocial factors in explaining this association. METHODS:
      Data were from 2,366 men and women, aged 55-85 years, participating in the
      Longitudinal Aging Study Amsterdam (LASA). Two indicators of socioeconomic status
      were used: education and income. Physical function was measured by self-reported
      physical ability over nine years of follow-up. RESULTS: In older adults, low
      socioeconomic status was related to a poorer level of physical function during
      nine years of follow-up. In subjects who were between 55 and 70 years old, there
      was an additional significant socioeconomic-differential decline in physical
      function, while socioeconomic differentials did not further widen in subjects 70
      years and older. Behavioral factors, mainly BMI and physical activity, largely
      explained the socioeconomic differences in physical function in the youngest age
      group, while psychosocial factors reduced socioeconomic status differences most
      in the oldest age group. CONCLUSION: The findings indicate age-specificity of
      both the pattern of socioeconomic status differences in function in older persons
      and the mechanisms underlying these associations.

PMID- 17022820
TI  - Genetic background determines response to hemostasis and thrombosis.
AB  - BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular
      diseases, the leading cause of mortality and morbidity in Western countries. Two
      inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility
      to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how
      these diverse genetic backgrounds influence pathways known to regulate thrombosis
      and hemostasis. The objective of this study was to evaluate thrombosis and
      hemostasis in these two inbred strains and determine the phenotypic response of
      A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were
      evaluated for differences in thrombosis and hemostasis. A thrombus was induced in
      the carotid artery by application of the exposed carotid to ferric chloride and
      blood flow measured until the vessel occluded. Bleeding and rebleeding times, as
      surrogate markers for thrombosis and hemostasis, were determined after clipping
      the tail and placing in warm saline. Twenty-one chromosome substitution strains,
      A/J chromosomes in a C57BL/6J background, were screened for response to the tail
      bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the
      A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two
      strains, but rebleeding time was markedly increased in the A/J mice compared to
      C57BL/6J mice. Coagulation times and tail morphology were similar, but tail
      collagen content was higher in A/J than C57BL/6J mice. Three chromosome
      substitution strains, B6-Chr5A/J, B6-Chr11A/J, and B6-Chr17A/J, were identified
      with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic
      for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when
      these two chromosome substitution strains, B6-Chr5A/J and B6-Chr17A/J, were
      crossed, the A/J phenotype was restored in these doubly heterosomic progeny.
      CONCLUSION: These results indicate that susceptibility to arterial thrombosis and
      haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome
      substitution strains were identified that expressed a phenotype similar to A/J
      for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the
      combination of two A/J QTL could restore the phenotype. The diverse genetic
      backgrounds and differences in response to vascular injury induced thrombosis and
      the tail bleeding assay, suggest the potential for identifying novel genetic
      determinants of thrombotic risk.

PMID- 17022821
TI  - Infection of human cytomegalovirus in cultured human gingival tissue.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection in the oral cavity plays an
      important role in its horizontal transmission and in causing viral-associated
      oral diseases such as gingivitis. However, little is currently known about HCMV
      pathogenesis in oral mucosa, partially because HCMV infection is primarily
      limited to human cells and few cultured tissue or animal models are available for
      studying HCMV infection. RESULTS: In this report, we studied the infection of
      HCMV in a cultured gingival tissue model (EpiGingival, MatTek Co.) and
      investigated whether the cultured tissue can be used to study HCMV infection in
      the oral mucosa. HCMV replicated in tissues that were infected through the apical
      surface, achieving a titer of at least 300-fold at 10 days postinfection.
      Moreover, the virus spread from the apical surface to the basal region and
      reduced the thickness of the stratum coreum at the apical region. Viral proteins
      IE1, UL44, and UL99 were expressed in infected tissues, a characteristic of HCMV
      lytic replication in vivo. Studies of a collection of eight viral mutants provide
      the first direct evidence that a mutant with a deletion of open reading frame
      US18 is deficient in growth in the tissues, suggesting that HCMV encodes specific
      determinants for its infection in oral mucosa. Treatment by ganciclovir abolished
      viral growth in the infected tissues. CONCLUSION: These results suggest that the
      cultured gingival mucosa can be used as a tissue model for studying HCMV
      infection and for screening antivirals to block viral replication and
      transmission in the oral cavity.

PMID- 17022823
TI  - Interest of major serum protein removal for Surface-Enhanced Laser
      Desorption/Ionization - Time Of Flight (SELDI-TOF) proteomic blood profiling.
AB  - BACKGROUND: Surface-Enhanced Laser Desorption/Ionization - Time Of Flight (SELDI
      TOF) has been proposed as new approach for blood biomarker discovery. However,
      results obtained so far have been often disappointing as this technique still has
      difficulties to detect low-abundant plasma and serum proteins. RESULTS: We used a
      serum depletion scheme using chicken antibodies against various abundant proteins
      to realized a pre-fractionation of serum prior to SELDI-TOF profiling. Depletion
      of major serum proteins by immunocapture was confirmed by 1D and 2D gel
      electrophoresis. SELDI-TOF analysis of bound and unbound (depleted) serum
      fractions revealed that this approach allows the detection of new low abundant
      protein peaks with satisfactory reproducibility. CONCLUSION: The combination of
      immunocapture and SELDI-TOF analysis opens new avenues into proteomic profiling
      for the discovery of blood biomarkers.

PMID- 17022822
TI  - Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival
      in patients with osteosarcoma.
AB  - BACKGROUND: Osteosarcoma is a very aggressive tumor with a propensity to
      metastasize and invade surrounding tissue. Identification of the molecular
      determinants of invasion and metastatic potential may guide the development of a
      rational strategy for devising specific therapies that target the pathways
      leading to osteosarcoma. METHODS: In this study, we used pathway-focused low
      density expression cDNA arrays to screen for candidate genes related to tumor
      progression. Expression patterns of the selected genes were validated by real
      time PCR on osteosarcoma patient tumor samples and correlated with clinical and
      pathological data. RESULTS: THBS3, SPARC and SPP1 were identified as genes
      differentially expressed in osteosarcoma. In particular, THBS3 was expressed at
      significantly high levels (p = 0.0001) in biopsies from patients with metastasis
      at diagnosis, which is a predictor of worse overall survival, event-free survival
      and relapse free survival at diagnosis. After chemotherapy, patients with tumors
      over-expressing THBS3 have worse relapse free survival. High SPARC expression was
      found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and
      correlated with the worst event-free survival (p = 0.03) and relapse free
      survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%)
      osteosarcomas correlating with better overall survival, event-free survival and
      relapse free survival at diagnosis. CONCLUSION: In this study three genes were
      identified with pattern of differential gene expression associated with a
      phenotypic role in metastasis and invasion. Interestingly all encode for proteins
      involved in extracellular remodeling suggesting potential roles in osteosarcoma
      progression. This is the first report on the THBS3 gene working as a stimulator
      of tumor progression. Higher levels of THBS3 maintain the capacity of
      angiogenesis. High levels of SPARC are not required for tumor progression but are
      necessary for tumor growth and maintenance. SPP1 is not necessary for tumor
      progression in osteosarcoma and may be associated with inflammatory response and
      bone remodeling, functioning as a good biomarker.

PMID- 17022824
TI  - Rank-statistics based enrichment-site prediction algorithm developed for
      chromatin immunoprecipitation on chip experiments.
AB  - BACKGROUND: High density oligonucleotide tiling arrays are an effective and
      powerful platform for conducting unbiased genome-wide studies. The ab initio
      probe selection method employed in tiling arrays is unbiased, and thus ensures
      consistent sampling across coding and non-coding regions of the genome. Tiling
      arrays are increasingly used in chromatin immunoprecipitation (IP) experiments
      (ChIP on chip). ChIP on chip facilitates the generation of genome-wide maps of in
      vivo interactions between DNA-associated proteins including transcription factors
      and DNA. Analysis of the hybridization of an immunoprecipitated sample to a
      tiling array facilitates the identification of ChIP-enriched segments of the
      genome. These enriched segments are putative targets of antibody assayable
      regulatory elements. The enrichment response is not ubiquitous across the genome.
      Typically 5 to 10% of tiled probes manifest some significant enrichment.
      Depending upon the factor being studied, this response can drop to less than 1%.
      The detection and assessment of significance for interactions that emanate from
      non-canonical and/or un-annotated regions of the genome is especially
      challenging. This is the motivation behind the proposed algorithm. RESULTS: We
      have proposed a novel rank and replicate statistics-based methodology for
      identifying and ascribing statistical confidence to regions of ChIP-enrichment.
      The algorithm is optimized for identification of sites that manifest low levels
      of enrichment but are true positives, as validated by alternative biochemical
      experiments. Although the method is described here in the context of ChIP on chip
      experiments, it can be generalized to any treatment-control experimental design.
      The results of the algorithm show a high degree of concordance with independent
      biochemical validation methods. The sensitivity and specificity of the algorithm
      have been characterized via quantitative PCR and independent computational
      approaches. CONCLUSION: The algorithm ranks all enrichment sites based on their
      intra-replicate ranks and inter-replicate rank consistency. Following the
      ranking, the method allows segmentation of sites based on a meta p-value, a
      composite array signal enrichment criterion, or a composite of these two
      measures. The sensitivities obtained subsequent to the segmentation of data using
      a meta p-value of 10-5, an array signal enrichment of 0.2 and a composite of
      these two values are 88%, 87% and 95%, respectively.

PMID- 17022825
TI  - Coloring the Mu transpososome.
AB  - BACKGROUND: Tangle analysis has been applied successfully to study proteins which
      bind two segments of DNA and can knot and link circular DNA. We show how tangle
      analysis can be extended to model any stable protein-DNA complex. RESULTS: We
      discuss a computational method for finding the topological conformation of DNA
      bound within a protein complex. We use an elementary invariant from knot theory
      called colorability to encode and search for possible DNA conformations. We apply
      this method to analyze the experimental results of Pathania, Jayaram, and Harshey
      (Cell 2002). We show that the only topological DNA conformation bound by Mu
      transposase which is biologically likely is the five crossing solution found by
      Pathania et al (although other possibilities are discussed). CONCLUSION: Our
      algorithm can be used to analyze the results of the experimental technique
      described in Pathania et al in order to determine the topological conformation of
      DNA bound within a stable protein-DNA complex.

PMID- 17022826
TI  - Highly active antiretroviral therapy and hospital readmission: comparison of a
      matched cohort.
AB  - BACKGROUND: Despite the known efficacy of highly active antiretroviral therapy
      (HAART), a large proportion of potentially-eligible HIV-infected patients do not
      access, and may stand to benefit from this treatment. In order to quantify these
      benefits in terms of reductions in hospitalizations and hospitalization costs, we
      sought to determine the impact of HAART on hospital readmission among HIV
      infected patients hospitalized at St. Paul's Hospital (SPH) in Vancouver, BC,
      Canada. METHODS: All patients admitted to a specialized HIV/AIDS ward at SPH
      (Apr. 1997-Oct. 2002) were selected and classified as being on HAART or not on
      HAART based upon their initial admission. Patients were then matched by their
      propensity scores, which were calculated based on patients' sociodemographics
      such as age, gender, injection drug use (IDU) status, and AIDS indication, and
      followed up for one year. Multivariate logistic regression was used to estimate
      the difference in the odds of hospital readmission between patients on and not on
      HAART. RESULTS: Out of a total 1084 patients admitted to the HIV/AIDS ward
      between 1997 and 2002, 662 were matched according to their propensity score; 331
      patients each on and not on HAART. Multivariate logistic regression revealed that
      patients on HAART had lower odds of AIDS hospital readmission (OR, 0.61; 95% CI,
      0.42-0.89) compared to patients not on HAART. Odds of readmission among patients
      on HAART were also significantly lower for non-IDU related readmission (OR, 0.73;
      95% CI, 0.53-0.99) and overall readmission (OR, 0.72; 95% CI, 0.53-0.98).
      CONCLUSION: Propensity score matching allowed us to reliably estimate the
      association between exposure (on or not on HAART) and outcome (readmitted to
      hospital). We found that HIV-infected patients who were potentially eligible for,
      but not on HAART had higher odds of being readmitted to hospital compared to
      those on HAART. Given the low level of uptake (31%) of HAART observed in our pre
      matched hospitalized cohort, a large potential to achieve clinical benefits,
      reduce hospitalization costs and possibly slow disease progression from improved
      HAART uptake still exists.

PMID- 17022827
TI  - Feasibility and validity of International Classification of Diseases based case
      mix indices.
AB  - BACKGROUND: Severity of illness is an omnipresent confounder in health services
      research. Resource consumption can be applied as a proxy of severity. The most
      commonly cited hospital resource consumption measure is the case mix index (CMI)
      and the best-known illustration of the CMI is the Diagnosis Related Group (DRG)
      CMI used by Medicare in the U.S. For countries that do not have DRG type CMIs,
      the adjustment for severity has been troublesome for either reimbursement or
      research purposes. The research objective of this study is to ascertain the
      construct validity of CMIs derived from International Classification of Diseases
      (ICD) in comparison with DRG CMI. METHODS: The study population included 551
      acute care hospitals in Taiwan and 2,462,006 inpatient reimbursement claims. The
      18th version of GROUPER, the Medicare DRG classification software, was applied to
      Taiwan's 1998 National Health Insurance (NHI) inpatient claim data to derive the
      Medicare DRG CMI. The same weighting principles were then applied to determine
      the ICD principal diagnoses and procedures based costliness and length of stay
      (LOS) CMIs. Further analyses were conducted based on stratifications according to
      teaching status, accreditation levels, and ownership categories. RESULTS: The
      best ICD-based substitute for the DRG costliness CMI (DRGCMI) is the ICD
      principal diagnosis costliness CMI (ICDCMI-DC) in general and in most categories
      with Spearman's correlation coefficients ranging from 0.938-0.462. The highest
      correlation appeared in the non-profit sector. ICD procedure costliness CMI
      (ICDCMI-PC) outperformed ICDCMI-DC only at the medical center level, which
      consists of tertiary care hospitals and is more procedure intensive. CONCLUSION:
      The results of our study indicate that an ICD-based CMI can quite fairly
      approximate the DRGCMI, especially ICDCMI-DC. Therefore, substituting ICDs for
      DRGs in computing the CMI ought to be feasible and valid in countries that have
      not implemented DRGs.

PMID- 17022828
TI  - fMRI-compatible rehabilitation hand device.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) has been widely used in
      studying human brain functions and neurorehabilitation. In order to develop
      complex and well-controlled fMRI paradigms, interfaces that can precisely control
      and measure output force and kinematics of the movements in human subjects are
      needed. Optimized state-of-the-art fMRI methods, combined with magnetic resonance
      (MR) compatible robotic devices for rehabilitation, can assist therapists to
      quantify, monitor, and improve physical rehabilitation. To achieve this goal,
      robotic or mechatronic devices with actuators and sensors need to be introduced
      into an MR environment. The common standard mechanical parts can not be used in
      MR environment and MR compatibility has been a tough hurdle for device
      developers. METHODS: This paper presents the design, fabrication and preliminary
      testing of a novel, one degree of freedom, MR compatible, computer controlled,
      variable resistance hand device that may be used in brain MR imaging during hand
      grip rehabilitation. We named the device MR_CHIROD (Magnetic Resonance Compatible
      Smart Hand Interfaced Rehabilitation Device). A novel feature of the device is
      the use of Electro-Rheological Fluids (ERFs) to achieve tunable and controllable
      resistive force generation. ERFs are fluids that experience dramatic changes in
      rheological properties, such as viscosity or yield stress, in the presence of an
      electric field. The device consists of four major subsystems: a) an ERF based
      resistive element; b) a gearbox; c) two handles and d) two sensors, one optical
      encoder and one force sensor, to measure the patient induced motion and force.
      The smart hand device is designed to resist up to 50% of the maximum level of
      gripping force of a human hand and be controlled in real time. RESULTS:
      Laboratory tests of the device indicate that it was able to meet its design
      objective to resist up to approximately 50% of the maximum handgrip force. The
      detailed compatibility tests demonstrated that there is neither an effect from
      the MR environment on the ERF properties and performance of the sensors, nor
      significant degradation on MR images by the introduction of the MR_CHIROD in the
      MR scanner. CONCLUSION: The MR compatible hand device was built to aid in the
      study of brain function during generation of controllable and tunable force
      during handgrip exercising. The device was shown to be MR compatible. To the best
      of our knowledge, this is the first system that utilizes ERF in MR environment.

PMID- 17022829
TI  - Treatment in the pediatric emergency department is evidence based: a
      retrospective analysis.
AB  - BACKGROUND: Our goal was to quantify the evidence that is available to the
      physicians of a pediatric emergency department (PED) in making treatment
      decisions. Further, we wished to ascertain what percentage of evidence for
      treatment provided in the PED comes from pediatric studies. METHODS: We conducted
      a retrospective chart review of randomly selected patients seen in the PED
      between January 1 and December 31, 2002. The principal investigator identified a
      primary diagnosis and primary intervention for each chart. A thorough literature
      search was then undertaken with respect to the primary intervention. If a
      randomized control trial (RCT) or a systematic review was found, the intervention
      was classified as level I evidence. If no RCT was found, the intervention was
      assessed by an expert committee who determined its appropriateness based on face
      validity (RCTs were unanimously judged to be both unnecessary and, if a placebo
      would have been involved, unethical). These interventions were classified as
      level II evidence. Interventions that did not fall into either above category
      were classified as level III evidence. RESULTS: Two hundred and sixty-two patient
      charts were reviewed. Of these, 35.9% did not receive a primary intervention. Of
      the 168 interventions assessed, 80.4% were evidence-based (level I), 7.1% had
      face validity (level II) and 12.5% had no supporting evidence (level III). Of the
      evidence-based interventions, 83.7% were supported by studies with mostly
      pediatric patients. CONCLUSION: Our study demonstrates that a substantial
      proportion of PED treatment decisions are evidence-based, with most based on
      studies in pediatric patients. Also, a large number of patients seen in the PED
      receive no intervention.

PMID- 17022830
TI  - The PTI1-like kinase ZmPti1a from maize (Zea mays L.) co-localizes with callose
      at the plasma membrane of pollen and facilitates a competitive advantage to the
      male gametophyte.
AB  - BACKGROUND: The tomato kinase Pto confers resistance to bacterial speck disease
      caused by Pseudomonas syringae pv. tomato in a gene for gene manner. Upon
      recognition of specific avirulence factors the Pto kinase activates multiple
      signal transduction pathways culminating in induction of pathogen defense. The
      soluble cytoplasmic serine/threonine kinase Pti1 is one target of Pto
      phosphorylation and is involved in the hypersensitive response (HR) reaction.
      However, a clear role of Pti1 in plant pathogen resistance is uncertain. So far,
      no Pti1 homologues from monocotyledonous species have been studied. RESULTS: Here
      we report the identification and molecular analysis of four Pti1-like kinases
      from maize (ZmPti1a, -b, -c, -d). These kinase genes showed tissue-specific
      expression and their corresponding proteins were targeted to different cellular
      compartments. Sequence similarity, expression pattern and cellular localization
      of ZmPti1b suggested that this gene is a putative orthologue of Pti1 from tomato.
      In contrast, ZmPti1a was specifically expressed in pollen and sequestered to the
      plasma membrane, evidently owing to N-terminal modification by myristoylation
      and/or S-acylation. The ZmPti1a:GFP fusion protein was not evenly distributed at
      the pollen plasma membrane but accumulated as an annulus-like structure which co
      localized with callose (1,3-beta-glucan) deposition. In addition, co-localization
      of ZmPti1a and callose was observed during stages of pollen mitosis I and pollen
      tube germination. Maize plants in which ZmPti1a expression was silenced by RNA
      interference (RNAi) produced pollen with decreased competitive ability. Hence,
      our data provide evidence that ZmPti1a plays an important part in a signalling
      pathway that accelerates pollen performance and male fitness. CONCLUSION: ZmPti1a
      from maize is involved in pollen-specific processes during the progamic phase of
      reproduction, probably in crucial signalling processes associated with regions of
      callose deposition. Pollen-sporophyte interactions and pathogen induced HR show
      certain similarities. For example, HR has been shown to be associated with cell
      wall reinforcement through callose deposition. Hence, it is hypothesized that
      Pti1 kinases from maize act as general components in evolutionary conserved
      signalling processes associated with callose, however during different
      developmental programs and in different tissue types.

PMID- 17022831
TI  - Relevance of cyclin D1b expression and CCND1 polymorphism in the pathogenesis of
      multiple myeloma and mantle cell lymphoma.
AB  - BACKGROUND: The CCND1 gene generates two mRNAs (cyclin D1a and D1b) through an
      alternative splicing at the site of a common A/G polymorphism. Cyclin D1a and b
      proteins differ in their C-terminus, a region involved in protein degradation and
      sub-cellular localization. Recent data have suggested that cyclin D1b could be a
      nuclear oncogene. The presence of cyclin D1b mRNA and protein has been studied in
      two hemopathies in which cyclin D1 could be present: multiple myeloma (MM) and
      mantle cell lymphoma (MCL). The A/G polymorphism of CCND1 has also been verified
      in a series of patients. METHODS: The expression of cyclin D1 mRNA isoforms has
      been studied by real-time quantitative PCR; protein isoforms expression,
      localization and degradation by western blotting. The CCND1 polymorphism was
      analyzed after sequencing genomic DNA. RESULTS: Cyclin D1 mRNA isoforms a and b
      were expressed in mantle cell lymphoma (MCL) and multiple myeloma (MM). Cyclin
      D1b proteins were present in MCL, rarely in MM. Importantly, both protein
      isoforms localized the nuclear and cytoplasmic compartments. They displayed the
      same short half-life. Thus, the two properties of cyclin D1b recognized as
      necessary for its transforming activity are missing in MCL. Moreover, CCND1
      polymorphism at the exon/intron boundary had no influence on splicing regulation
      in MCL cells. CONCLUSION: Our results support the notion that cyclin D1b is not
      crucial for the pathogenesis of MCL and MM.

PMID- 17022832
TI  - The quality of telemedicine research.

PMID- 17022833
TI  - Satellite communications for supporting medical care in the aftermath of
      disasters.
AB  - At present, mobile phones are not a useful tool for medical control during a
      disaster. We have estimated the number of satellite channels that would be needed
      for telemedicine in a major disaster using the Erlang B equation. This indicated
      that 29 satellite channels would be sufficient for the operation of a
      telemedicine system for hospital-to-hospital communications during a major
      disaster in Japan. Governments at local and national levels in Japan, as well as
      private organizations, require an independent satellite telecommunication
      infrastructure to deal with the aftermath of disasters.

PMID- 17022834
TI  - Defining the needs of a telemedicine service.
AB  - While telemedicine programme objectives, technologies and even philosophies will
      differ, certain common factors that enhance programme success can be identified.
      For example, a programme design which is driven by technological imperatives is
      likely to fail. It must also be recognized that telemedicine programmes cannot
      force remote sites to use their services. Thus developers must assess the needs
      for the proposed telemedicine service from a clinical, economic and technical
      perspective. From a clinical perspective, it is important to remember that
      certain clinical services can be provided via telemedicine while others cannot.
      Programme developers must recognize the significant role of the remote team in
      sustaining services; the on-site presenter is essential for the successful
      practice of telemedicine. Evaluating a telemedicine programme should be viewed as
      an integral step in its design and implementation. One site may define
      effectiveness in terms of access to services while another may measure success by
      cost savings. The success of future telemedicine programmes will be strongly
      related to their ability to recognize that they should be used to enhance current
      health-care delivery rather than to replace it.

PMID- 17022835
TI  - Telepsychiatry improves paediatric behavioural health care in rural communities.
AB  - In the US, children with special health care needs are underserved by both the
      medical and educational systems. This problem is especially serious in rural
      states. Telemedicine is a technique that can reduce these gaps in service and
      help connect the two systems. The technology required has become cheaper and more
      accessible. Progress on reimbursement for such services has also been made. For
      some years, we have provided telepsychiatry for children in Washington State
      using videoconferencing. Interviews with families and service providers were
      conducted in Washington and Missouri. Some parents reported that their child
      actually preferred telepsychiatry to conventional consultation. The
      telepsychiatry service model was built on the existing system of outreach
      clinics, thus involving specialists who were familiar with the community and who
      were known and trusted by the community. Before starting, we ensured that all
      relevant service delivery agencies and providers were comfortable about using
      videoconferencing as a method of service delivery. In the 18-month period ending
      in March 2003, three providers in Seattle saw 159 patients by telepsychiatry and
      210 patients face-to-face at the hospital clinic. The main barrier to further
      growth of the telepsychiatry service is the absence of reimbursement for
      telepsychiatry.

PMID- 17022836
TI  - A systematic review of the methodology of telemedicine evaluation in patients
      with postural and movement disorders.
AB  - We reviewed the methodology used in telemedicine research concerning patients
      with postural and movement disorders. Literature searches were performed using
      various computerized databases through to October 2005. Twenty-two studies met
      the criteria for review. Two broad models of telemedicine delivery were
      represented in the literature: (1) telemedicine between health-care professionals
      at each telemedicine site (n=16) and (2) telemedicine between health-care
      professionals and a patient at a remote site (n=6). Disparate research
      methodologies were used to investigate these two models. Most studies were
      limited to investigating the technical feasibility and acceptability of a
      telemedicine service rather than focusing on the overall effect of introducing
      the telemedicine service into routine health care. Nonetheless, it is possible to
      conclude that telemedicine is acceptable for both patients and professionals when
      used in rehabilitation. Since the two models of telemedicine evaluation tend to
      explore different outcomes (diagnostic accuracy versus health status), it is
      recommended that separate methodologies should be used. In contrast to
      evaluations of telemedicine model 2, randomized controlled trials appear to be
      less valuable for telemedicine model 1.

PMID- 17022837
TI  - Performance of a wireless telemedicine system in a hospital accident and
      emergency department.
AB  - We developed a mobile, wireless videoconferencing system suitable for use in a
      hospital accident and emergency (A&E) department. Four consultants, eight junior
      doctors and 11 nurses working in the A&E department tested the system.
      Transmission of three types of data (audio, still images and video) was tested.
      The audio for the breath and heart sounds was judged to have some disturbance.
      One consultant rated the diagnostic quality as good and one rated it as fair. The
      quality of the still images was judged to be from fair to excellent. The quality
      of the video was rated as good. Possible interference between the wireless local
      area network and various medical devices in the A&E department were examined, but
      none was detected. The four consultants who tested the system were very positive
      in their initial comments. Eight of the 11 nurses remained sceptical about its
      use. Of a total of 20 patients who answered a survey, 13 were slightly anxious
      about the use of the system to transmit their data to a distant point. Overall,
      the performance of the system was satisfactory for use in the A&E role.

PMID- 17022838
TI  - Consultation times in emergency telemedicine using realtime videoconferencing.
AB  - We reviewed 2135 consecutive emergency teleconsultations, which were received at
      an academic emergency department from state correctional facilities. During the
      52-week study period, an average of 5.8 video-consultations per day were
      performed. A total of 1522 consultations (71%) had complete start and end
      consultation times, and were included in the analysis. Of these, 923 were managed
      primarily by emergency medicine residents and physician assistants, while the
      remaining 599 were managed by attending physicians alone. Following consultation,
      the disposition of the patients included 940 who were transported to the
      emergency department, 351 who were discharged to the general facility population
      and 193 who were admitted to the local infirmary. Overall, 38% of patients
      avoided a journey to the emergency department. The average consultation time was
      17 min (95% confidence interval [CI], 10-24). The average consultation time for
      residents and physician assistants was 16 min (95% CI, 8-24) and it was 19 min
      (95% CI, 11-27) for attending physicians. Consultation time for patients not
      transported to the emergency room was 21 min (95% CI, 13-29), while for patients
      transferred to an emergency department, consultation time was 15 min (95% CI, 9
      21). These results may assist in planning the workforce requirements for
      emergency department-based telemedicine services.

PMID- 17022839
TI  - Patient-nurse-doctor interaction in general practice teleconsultations--a
      qualitative analysis.
AB  - We analysed the interaction in doctor-nurse-patient teleconsultations in primary
      care. A qualitative analysis was performed of 30 primary care teleconsultations
      in northeastern Finland. The male doctor was the same in all consultations. One
      of the trained nurses appeared in 27 consultations. The analysis followed the
      methodological principles of the grounded theory approach. The interaction in the
      doctor-nurse-patient triad was complex. The doctor had to concentrate on many
      things at the same time and undivided attention to the patient was not always
      possible. The nurse assumed an active role and was a facilitator of the
      interaction, an advocate for the patient, a secretary for the doctor and a
      mediator of the doctor's therapeutic influence. The patients frequently turned to
      the nurse for information. The role of interpersonal dynamics in telemedical
      encounters is important. Both the doctor and the nurse need to learn new skills
      to perform teleconsultations jointly.

PMID- 17022840
TI  - An analysis of 46 static telecytology cases over a period of two years.
AB  - We analysed 46 telecytology cases sent from two rural hospitals about 500 km from
      a tertiary cancer centre. The cases were submitted for second opinion over a
      period of two years and evaluated using a static store and forward telecytology
      approach. A total of 715 digital images were studied (average 15 per case). Forty
      one of the 46 cases (89%) were reported within 3 days and 54% of cases were
      reported within one working day. The aspiration smears and images were found to
      be of diagnosable quality in 89 and 93% of the cases, respectively. The
      diagnostic concordance was assessed by comparing the telecytology diagnosis,
      glass slide diagnosis and final histopathology diagnosis (when available). A
      clinically useful diagnosis was rendered in 91% cases with 74% complete
      concordance. Five out of 46 cases (11%) were deferred for glass slide review.
      Store and forward telecytology using the Internet is a rapid and effective method
      of providing expert diagnosis in cytology.

PMID- 17022841
TI  - Validation of 12-lead tele-electrocardiogram transmission in the real-life
      scenario of acute coronary syndrome.
AB  - A 12-lead electrocardiogram (ECG) recorded in patients with acute coronary
      syndrome (ACS) was transmitted to a call centre via telephone (tele-ECG). In 120
      patients (mean age 64 years) referred to hospitals because of ACS, a standard 12
      lead ECG and a tele-ECG recorded at the same time were compared by two
      cardiologists and one internist independently and blindly. Conduction times
      exhibited very good agreement between standard and tele-ECG with reliability
      coefficients (R) of 0.91, 0.86 and 0.89 for the PQ-, QRS- and QT interval,
      respectively. Rhythm analysis was correct in 99% of the cases. Negative T waves,
      ST-segment elevation and depression were detected with very high agreement in the
      tele-ECG exhibiting kappa (kappa) coefficients between 0.75 and 0.96. The correct
      ECG diagnosis of ST-elevation myocardial infarction (STEMI) was possible with
      excellent agreement between standard and tele-ECG, showing kappa coefficients of
      0.96, 0.99 and 0.99, respectively, for three investigators. The 12-lead tele-ECG
      recorder proved accurate for the detection of acute STEMI.

PMID- 17022842
TI  - Telecytology--are we ready?

PMID- 17022843
TI  - Satellite applications for telehealth in the developing world.

PMID- 17022844
TI  - Efficacy and tolerability of ropinirole in patients with restless legs syndrome
      and a baseline IRLS total score > or = 24 points--data from the ropinirole
      clinical trial programme.
AB  - OBJECTIVE: Results from one of the largest clinical trial programmes to date of a
      dopamine agonist in patients with primary restless legs syndrome (RLS) have
      demonstrated that ropinirole, 0.25-4.0 mg once daily 1-3 hours before bedtime, is
      associated with significant improvements in RLS symptoms, sleep parameters and
      quality-of-life measures, compared with placebo. Analyses were conducted in a
      subpopulation of patients with a baseline score on the International Restless
      Legs Scale (IRLS) of at least 24 points. RESEARCH DESIGN AND METHODS: Data was
      pooled from four, 12-week, pivotal studies: RESET PLM and TREAT RLS 1, 2 and US.
      MAIN OUTCOME MEASURES: Covariate analysis demonstrated that the magnitude of
      treatment difference between ropinirole and placebo for change in IRLS total
      score (a measure of RLS symptom severity) increased with increasing baseline IRLS
      total score. Mean treatment difference was > 3 points in patients with a baseline
      total score > or = 24. Among this population, ropinirole treatment was associated
      with significant reduction in RLS symptom severity compared with placebo, along
      with significant improvements in global symptoms and sleep measures. A treatment
      benefit was also observed for measures of quality of life. Ropinirole is well
      tolerated in this patient population. CONCLUSIONS: Patients with primary RLS and
      baseline IRLS total score > or = 24 gain clinically meaningful benefits from
      ropinirole treatment. As with the overall population in the ropinirole clinical
      trial programme, ropinirole was associated with improvements in RLS symptoms,
      global symptoms, sleep and quality of life and was well tolerated in patients
      with a baseline IRLS total score > or = 24.

PMID- 17022845
TI  - Clinical spectrum of the osmotic-controlled release oral delivery system (OROS),
      an advanced oral delivery form.
AB  - BACKGROUND: The osmotic-controlled release oral delivery system, OROS, is an
      advanced drug delivery technology that uses osmotic pressure as the driving force
      to deliver pharmacotherapy, usually once-daily, in several therapeutic areas.
      OBJECTIVE: The purpose of this review is to discuss the evolution of OROS
      technology and examine the many therapeutic areas where OROS products are being
      used. METHODS: A search of Medline and EMBASE were performed using the keywords
      'OROS' and 'osmotic delivery' for the period January 1990 to June 2005. Data were
      also obtained from the manufacturers' websites and associated publications.
      RESULTS: OROS technology has evolved over the last 30 years, resulting in four
      systems: the elementary osmotic pump; the two-layer osmotic push-pull tablet; the
      advanced longitudinally compressed tablet multilayer formulation; and, the L-OROS
      system. OROS technology is employed for drug delivery in many therapeutic areas
      including: cardiovascular medicine, endocrinology, urology, and central nervous
      system (CNS) therapeutics. Two calcium channel blockers utilizing OROS technology
      for the treatment of hypertension are nifedipine and verapamil. Glipizide
      extended-release is used for the treatment of type 2 diabetes. Doxazosin is used
      for the treatment of benign prostatic hyperplasia, and oxybutynin for overactive
      bladder. Most recent developments are with drugs that affect the CNS, including
      the use of methylphenidate for treatment of attention deficit hyperactivity
      disorder, paliperidone extended-release and OROS hydromorphone, which are under
      clinical development for schizophrenia and chronic pain, respectively.
      CONCLUSIONS: Drug delivery using the various OROS products can result in an
      improved safety profile, stable drug concentrations, uniform drug effects, and
      reduced dosing frequency. OROS technology has also enabled the use of an
      effective starting dose, without the need for dose titration, which allows the
      achievement of symptom control much earlier than that observed with immediate
      release preparations. Such attributes can enhance patient compliance and
      convenience, thereby ensuring efficacy and improving patient outcomes.

PMID- 17022846
TI  - A pharmacokinetic study investigating the rate of absorption of a 500 mg dose of
      a rapidly absorbed paracetamol tablet and a standard paracetamol tablet.
AB  - OBJECTIVE: A rapidly absorbed tablet formulation of paracetamol containing sodium
      bicarbonate (PS) has been previously shown to be absorbed at least twice as fast
      as a standard paracetamol tablet (P) at a 1 g dose. In South America and Asia it
      is customary for patients to take a 500 mg dose of analgesic. The objective of
      this pharmacokinetic study was to compare the rate of absorption of PS versus P
      at a 500 mg dose. RESEARCH DESIGN AND METHODS: An open, randomized, single dose,
      cross-over study. Thirty Hispanic healthy volunteers randomly received a 500 mg
      dose taken orally with 50 mL of water 2 h after a standard breakfast. Blood
      samples were taken up to 10 h post-dose. Plasma concentrations of paracetamol
      were determined by HPLC with UV detection. MAIN OUTCOME MEASURES: AUC(0-30 min),
      C(plasma 30 min) and T(max) were analyzed non-parametrically by the Wilcoxon's
      rank sum test. A linear mixed effects model was used to analyze the
      logarithmically transformed AUC(0-alpha) and C(max). Bioequivalence was accepted
      if the 90% confidence intervals (CI) for the ratio of the means of the primary
      pharmacokinetic variable AUC(0-alpha) lay completely within the range 0.80-1.25.
      RESULTS: AUC(0-30 min) and C(plasma 30 min) were significantly greater and T(max)
      was significantly shorter (all p < 0.0001) for PS versus P. The formulations were
      bioequivalent for AUC(0-alpha) (90% CI 0.99:1.05) and no statistical difference
      was seen for C(max) (95% CI 0.91:1.14). CONCLUSIONS: Paracetamol was absorbed at
      least twice as fast from PS compared to P at a 500 mg dose. The extent of
      absorption was equivalent for both formulations.

PMID- 17022847
TI  - Comments on The cost-effectiveness of bimatoprost, latanoprost and timolol in
      treatment of primary open angle glaucoma in five European countries.

PMID- 17022848
TI  - Assessing the total costs of blood delivery to hospital oncology and haematology
      patients.
AB  - OBJECTIVE: To determine direct costs associated with a blood transfusion session
      in two hospital settings. RESEARCH DESIGN AND METHODS: The study was conducted in
      two United Kingdom hospital sites during April 2004. Transfusion sessions for
      patients receiving units of red blood cells within either haematology or oncology
      departments were followed using time and motion techniques to measure the direct
      costs. Other data were collected from the centres to calculate the cost of
      disposables, blood wastage and blood bank machines. RESULTS: Total mean staff
      cost per transfusion of 2 units was 37.24 pounds sterling (9.68 pounds sterling
      for blood bank and 27.56 pounds sterling for ward procedures). The mean cost of
      disposables was 13.25 pounds sterling and the mean cost for blood products was
      287.56 pounds sterling. The mean cost of wastage was 11.86 pounds sterling per
      transfusion. After including other derived costs, such as hospital stay, the mean
      cost for a transfusion of 2 units of blood was estimated to be 546.12 pounds
      sterling. CONCLUSION: This study estimates the cost of an average blood
      transfusion of 2 units to be 546.12 pounds sterling. It should be noted that
      significant indirect costs, such as those incurred by patients, their carers and
      societal costs, have not been considered. Against the background of finite blood
      resources and other factors such as patient quality of life, blood transfusion
      may not represent the best choice for patient care. Alternative treatments should
      be considered.

PMID- 17022849
TI  - painDETECT: a new screening questionnaire to identify neuropathic components in
      patients with back pain.
AB  - OBJECTIVE: Nociceptive and neuropathic components both contribute to pain. Since
      these components require different pain management strategies, correct pain
      diagnosis before and during treatment is highly desirable. As low back pain (LBP)
      patients constitute an important subgroup of chronic pain patients, we addressed
      the following issues: (i) to establish a simple, validated screening tool to
      detect neuropathic pain (NeP) components in chronic LBP patients, (ii) to
      determine the prevalence of neuropathic pain components in LBP in a large-scale
      survey, and (iii) to determine whether LBP patients with an NeP component suffer
      from worse, or different, co-morbidities. METHODS: In co-operation with the
      German Research Network on Neuropathic Pain we developed and validated the
      painDETECT questionnaire (PD-Q) in a prospective, multicentre study and
      subsequently applied it to approximately 8000 LBP patients. RESULTS: The PD-Q is
      a reliable screening tool with high sensitivity, specificity and positive
      predictive accuracy; these were 84% in a palm-top computerised version and 85%,
      80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire. In
      an unselected cohort of chronic LBP patients, 37% were found to have
      predominantly neuropathic pain. Patients with NeP showed higher ratings of pain
      intensity, with more (and more severe) co-morbidities such as depression,
      panic/anxiety and sleep disorders. This also affected functionality and use of
      health-care resources. On the basis of given prevalence of LBP in the general
      population, we calculated that 14.5% of all female and 11.4% of all male Germans
      suffer from LBP with a predominant neuropathic pain component. CONCLUSION:
      Simple, patient-based, easy-to-use screening questionnaires can determine the
      prevalence of neuropathic pain components both in individual LBP patients and in
      heterogeneous cohorts of such patients. Since NeP correlates with more intense
      pain, more severe co-morbidity and poorer quality of life, accurate diagnosis is
      a milestone in choosing appropriate therapy.

PMID- 17022850
TI  - Effect of gliclazide modified release on adiponectin, interleukin-6, and tumor
      necrosis factor-alpha plasma levels in individuals with type 2 diabetes mellitus.
AB  - OBJECTIVE: The aim of the study was to evaluate the effect of gliclazide modified
      release (MR) treatment on adiponectin, interleukin 6 (IL-6), and tumor necrosis
      factor-alpha (TNF-alpha) plasma concentrations in type 2 diabetic patients.
      RESEARCH DESIGN AND METHODS: 24 randomly selected type 2 diabetic patients, aged
      61.2 +/- 15.4 years, with poorly controlled glucose level (mean glycated
      hemoglobin [HbA1c] 7.6 +/- 1.1%) despite treatment with diet and/or oral
      hypoglycemic agents, were included in the study. All of the patients, after a 2
      week run-in period, were given gliclazide MR for 12 weeks. At baseline, and after
      gliclazide MR treatment, HbA(1c) and plasma concentrations of IL-6, TNF-alpha,
      and adiponectin were measured. RESULTS: Gliclazide MR treatment produced
      significant reductions in fasting plasma glucose (from 7.6 +/- 1.4 to 6.6 +/- 1.2
      mmol/L, p < 0.01), HbA(1c) (from 7.6 +/- 1.1 to 6.9 +/- 0.8%, p < 0.01), and
      plasma IL-6 concentrations (from 2.5 +/- 1.8 to 1.8 +/- 1.2 pg/mL, p < 0.05). A
      significant increase in plasma adiponectin level was noted (from 6.4 +/- 3.3 to
      7.6 +/- 4.4 mug/mL, p < 0.05). Plasma TNF-alpha concentrations and homeostasis
      model assessment of insulin resistance (HOMA-IR) decreased after treatment, but
      these changes did not reach statistical significance. CONCLUSIONS: Gliclazide MR
      improves glycemic control and, in addition, has a positive influence on the
      plasma level of some inflammatory markers and adiponectin. Increased plasma
      adiponectin and decreased plasma IL-6, and TNF-alpha levels may explain, at least
      in part, the anti-atherogenic action of this drug reported elsewhere.

PMID- 17022851
TI  - Comments on Initial experience with teriparatide in the United States.

PMID- 17022852
TI  - Relationship between hemoglobin level and quality of life in anemic patients with
      chronic kidney disease receiving epoetin alfa.
AB  - OBJECTIVES: To evaluate the relationship between hemoglobin (Hb) level and
      quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease
      receiving epoetin alfa. PATIENTS AND METHODS: A post-hoc analysis using data from
      a multicenter, open-label, prospective study of epoetin alfa for anemia in
      patients with chronic kidney disease not on dialysis was conducted. The
      relationship between Hb and QOL was analyzed using correlation and longitudinal
      analyses, the latter adjusting for sample selection bias. The Linear Analog Scale
      Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used
      to measure QOL. The impact of an incremental 1 g/dL increase in Hb level on LASA
      and KDQ scores was determined using an incremental analysis. RESULTS: A total of
      1183 and 1044 patients formed the study populations for the LASA and KDQ
      analyses, respectively. There was a positive and significant relationship between
      Hb levels and QOL (p < 0.05). Using non-linear regression analysis, we
      characterized the sigmoid-shape of the relationship between Hb levels and QOL
      scores. Hemoglobin change was a statistically significant determinant of QOL
      improvement for both LASA and KDQ scales (p < 0.05). The model predicted that,
      based on a 2 unit change in Hb, the greatest incremental QOL improvement per unit
      of Hb increase occurred when Hb was in the range of 11 to 12 g/dL. CONCLUSIONS:
      This study demonstrates that, beyond the well-known relationship between Hb
      increases and QOL improvements, the maximal incremental gain in QOL occurred when
      Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non
      dialysis chronic kidney disease until their Hb level reaches 12 g/dL will result
      in the greatest QOL improvement per Hb unit increase. The analyses were conducted
      based on an open-label study of epoetin alfa and could be further validated using
      a randomized, controlled trial, comparing incremental gains in QOL associated
      with treatment initiation at varying levels of Hb across arms.

PMID- 17022853
TI  - Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4
      inhibitor sitagliptin when co-administered in patients with type 2 diabetes.
AB  - OBJECTIVE: As part of the clinical development of sitagliptin, a dipeptidyl
      peptidase-4 inhibitor, for the treatment of type 2 diabetes, the potential for
      pharmacokinetic interactions with other antihyperglycemic agents used in managing
      patients with type 2 diabetes are being carefully evaluated. The purposes of this
      study were to evaluate the tolerability of co-administered sitagliptin and
      metformin and effects of sitagliptin on metformin pharmacokinetics as well as
      metformin on sitagliptin pharmacokinetics under steady-state conditions. METHODS:
      This placebo-controlled, multiple-dose, crossover study in patients with type 2
      diabetes assessed the tolerability of co-administered sitagliptin (50 mg b.i.d.)
      with metformin (1000 mg b.i.d.). Patients received, in a randomized crossover
      manner, three treatments (each of 7 days duration): 50 mg sitagliptin twice daily
      and placebo to metformin twice daily; 1000 mg of metformin twice daily and
      placebo to sitagliptin twice daily; concomitant administration of 50 mg of
      sitagliptin twice daily and 1000 mg of metformin twice daily. Following dosing on
      Day 7 of each treatment period, these pharmacokinetic parameters were determined
      for plasma sitagliptin and metformin: area under the plasma concentrations-time
      curve over the dosing interval (AUC(0-12h)), maximum observed plasma
      concentrations (C(max)), and time of occurrence of maximum observed plasma
      concentrations (T(max)). Renal clearance was also determined for sitagliptin.
      RESULTS: In this study, no adverse experiences were reported by 11 of 13
      patients. Two patients had adverse experiences, which were not related to study
      drugs as determined by the investigators. The mean metformin plasma concentration
      time profiles were nearly identical with or without sitagliptin co-administration
      [metformin AUC(0-12h) geometric mean ratio (GMR; [metformin +
      sitagliptin]/metformin)] was 1.02 (90% CI 0.95, 1.09). Similarly metformin
      administration did not alter the plasma sitagliptin pharmacokinetics [sitagliptin
      AUC(0-12 h) GMR ([sitagliptin + metformin]/sitagliptin)] was 1.02 (90% CI 0.97,
      1.08) or renal clearance of sitagliptin. No efficacy measurements (glycosylated
      hemoglobin or fasting plasma glucose) were obtained during this study. Urinary
      pharmacokinetics for metformin were not determined due to the lack of effect of
      sitagliptin on plasma metformin pharmacokinetics. CONCLUSIONS: In this study, co
      administration of sitagliptin and metformin was generally well tolerated in
      patients with type 2 diabetes and did not meaningfully alter the steady-state
      pharmacokinetics of either agent.

PMID- 17022854
TI  - Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative
      analgesia after surgery for breast cancer.
AB  - OBJECTIVE: To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g
      on a 24-h dosing schedule in this randomised, double-blinded study of 40 ASA I
      III (American Society of Anesthesiologists classification of physical status)
      patients undergoing surgery for breast cancer. RESEARCH DESIGN AND METHODS:
      General anaesthesia using remifentanil and propofol was performed for surgery.
      The patients were randomly allocated to two groups, receiving infusions of
      paracetamol 1 g/100 mL (Para Group) or of dipyrone 1 g/100 mL (Dipy Group) 30 min
      before arrival in the recovery area and every 6 h up to 24 h postoperatively. All
      patients had unrestricted access to opioid rescue medication via an IV patient
      controlled analgesia (PCA) device. MAIN OUTCOME MEASURES: The primary variables
      for clinical equivalence were the differences between the mean values for pain
      scores at rest and pain scores on coughing over 30 h postoperatively. The
      equivalence margin was determined as +/-10 mm on the visual analogue scale (VAS).
      RESULTS: Regarding pain scores at rest, the 90% CI of the mean differences
      between the treatment groups over 30 h postoperatively was found to be within the
      predefined equivalence margin [+7.5/-6.2], and the CI values for pain scores on
      coughing [+7.3/-9.0] were similar. The two groups did not differ in cumulative
      opioid rescue consumption (Dipy-Group 14.8 +/- 17.7 mg vs. Para Group 12.1 +/-
      8.8 mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 +/- 2.8 mg vs.
      Para Group 1.3 +/- 2.8 mg, p = 0.545). Five patients in the Dipy Group
      experienced hypotension in contrast to none in the Para Group (p = 0.047). There
      were no significant between-treatment differences for other adverse events,
      patient satisfaction scores (p = 0.4) or quality of recovery scores (p = 0.3).
      CONCLUSION: IV paracetamol 1 g is clinically equivalent to IV dipyrone 1 g for
      postoperative analgesia after surgery for breast cancer.

PMID- 17022855
TI  - Effect on blood pressure control of switching from valsartan monotherapy to
      losartan/hydrochlorothiazide in Asian patients with hypertension: results of a
      multicentre open-label trial.
AB  - STUDY DESIGN: An open-label, multicentre study was conducted to evaluate the
      antihypertensive efficacy of a 4-week course of losartan 50 mg plus
      hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose
      blood pressure had previously been treated with but not controlled by valsartan
      80 mg. METHODS: A total of 237 eligible patients with mean trough sitting
      diastolic blood pressure (SiDBP) 95-115 mmHg and a mean trough sitting systolic
      blood pressure (SiSBP) < 190 mmHg entered the baseline period of treatment with
      valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90 mmHg
      and who were not excluded for other reasons were then switched to a single-tablet
      formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily
      for a further 4 weeks. RESULTS: Mean SiDBP (study primary endpoint) at the end of
      combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study
      secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions
      after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5
      mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (p < or = 0.001
      for both outcomes). The goal of SiDBP < or = 90 mmHg was attained in 72% of the
      patients previously not controlled to the same level by valsartan 80 mg/day.
      Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally
      well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5
      mg combination was > 99%. CONCLUSION: These results demonstrate that in Asian
      patients who do not reach the goal of mean trough SiDBP < or = 90 mmHg with
      valsartan monotherapy at 80 mg once-daily, switching to a single-tablet
      combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well
      tolerated, provides effective control of blood pressure and is an excellent
      choice to achieve blood pressure reduction goals.

PMID- 17022856
TI  - Evaluating hospital costs in type 2 diabetes care: does the choice of the model
      matter?
AB  - BACKGROUND: Awareness of the economic burden of diabetes has led to a number of
      studies on economic issues. However, comparison among cost-of-illness studies is
      problematic because different methods are used to arrive at a final cost
      estimate. OBJECTIVE: The aim of the study is to show how estimates of
      hospitalisation costs for diabetic patients can vary significantly in relation to
      the statistical method adopted in the analysis. RESEARCH DESIGN AND METHODS: The
      study analyses diabetic patients' costs as a function of demographic and clinical
      covariates, by applying the following statistical survival models: the parametric
      survival model assuming Weibull distribution, the Cox proportional hazard (PH)
      model and the Aalen additive regression for modelling costs. The Aalen approach
      is robust both for the non proportionality in hazard and for departures from
      normality. In addition it is able to easily model the effect of covariates on the
      extreme costs. This cost analysis is based on data collected for a retrospective
      observational study analysing repeated hospitalisations (N = 4816) in a cohort of
      3892 diabetic patients. RESULTS: There is agreement in all models with the
      effects of the considered covariates (age, sex, duration of disease and presence
      of other pathologies). An effect of over- or under-estimation, according to the
      chosen model due to arguably inappropriate model fitting, was observed, being
      more evident for some specific profiles of the patients, and overall accounting
      for as much as 20% of the estimated effect. The Aalen model was able to cope with
      all the other models in furnishing unbiased estimates with the advantage of a
      greater flexibility in representing the covariates' effect on the cost process.
      CONCLUSIONS: An appropriate choice of the model is crucial in avoiding
      misinterpretation of cost determinants of type 2 diabetes care. For our data set
      the Aalen model proved itself to be a realistic and informative way to
      characterise the effect of covariates on costs.

PMID- 17022857
TI  - Effect of growth hormone treatment on trunk fat accumulation in adult GH
      deficient Japanese patients: a randomised, placebo-controlled trial.
AB  - OBJECTIVE: Patients with growth hormone deficiency (GHD), both Japanese and
      Caucasian, have an abnormal body composition with pronounced abdominal obesity.
      This study aimed to evaluate changes in trunk fat with GH treatment. DESIGN:
      Double-blind, placebo-controlled study. PATIENTS AND MEASUREMENTS: Sixty-one
      Japanese adult GH deficient patients (mean age 37 years) were randomised to
      either GH, titrated to 0.012 mg/kg/day, (n = 30) or placebo (n = 31) for 24
      weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated
      at a central laboratory for trunk fat, total body fat and lean body mass. Serum
      lipid levels were also determined centrally. RESULTS: At baseline, 26 (42.6%)
      patients had a body mass index (BMI) > or = 25 kg/m(2), the threshold for obesity
      related complications for Japanese subjects. Median trunk fat mass (FM) was > or
      = 9.0 kg for each treatment and gender group, higher than the cut-off for
      increased age-adjusted risk for cardiovascular complications reported in the
      normal Japanese population. After 24 weeks of GH treatment, the change in
      percentage trunk FM was -3.4 +/- 0.6%, versus 0.4 +/- 0.6% with placebo (p <
      0.001). Change in total body FM was -2.8 +/- 0.5% with GH and 0.0 +/- 0.5% with
      placebo, indicating that the decrease in trunk fat was more pronounced than for
      total body fat. Total and low density lipoprotein (LDL)-cholesterol were both
      significantly (p < 0.001) decreased compared with placebo. One patient
      discontinued due to a subdural haematoma and one had GH dose reduced due to
      hyperglycaemia. CONCLUSIONS: Japanese patients with GHD have abnormal central fat
      accumulation, which is reduced by GH treatment over 24 weeks. This may reduce
      cardiovascular risk but the GH dose should be individualised to maintain IGF-I in
      the normal range.

PMID- 17022858
TI  - Patient experience with follitropin alfa prefilled pen versus previously used
      injectable gonadotropins for ovulation induction in oligoanovulatory women.
AB  - OBJECTIVE: To evaluate patient satisfaction with the follitropin alfa prefilled
      pen (Gonal-f RFF Pen), compared with previously used injectable gonadotropins
      (vial/ampoules and syringe), in women undergoing ovulation induction (OI).
      RESEARCH DESIGN AND METHODS: Women aged 18-40 years undergoing OI for
      oligoanovulatory infertility were enrolled from nine US fertility centers in this
      prospective, open-label clinical trial. Participants received recombinant
      follitropin alfa using a prefilled pen. Patient satisfaction was determined using
      a pre-treatment questionnaire to assess gonadotropin treatments undertaken within
      6 months of study initiation and an in-treatment questionnaire to assess
      satisfaction with the prefilled pen. MAIN OUTCOME MEASURES: The primary endpoint
      was the proportion of patients who preferred the prefilled pen compared to
      previous injectable gonadotropin therapies. Efficacy and safety were also
      assessed. RESULTS: Seventy-three subjects were screened for the study; 62
      enrolled, were treated with the follitropin alfa pre-filled pen, and 61 completed
      the in-treatment questionnaire. Sixty-one of 61 patients who stated a preference
      preferred the prefilled pen to previous injectable gonadotropin therapies (61/61;
      100%; 95% confidence interval: [94.1-100.0%]). One patient did not state a
      preference. Of these 61 patients, 54 (89%) found that the prefilled pen
      instructions were easy to understand compared to 17 of 59 (29%) who thought
      instructions for the conventional syringes were easy to understand. When
      preparing their dose, significantly fewer patients contacted their healthcare
      provider two or more times during the treatment cycle when receiving treatment
      with the prefilled pen (2/61, 3%) than during the first treatment cycle with
      prior gonadotropin treatment, 11/59 (19%, p = 0.007). The pen interfered slightly
      or not at all with patients' normal daily activities in 61 of 61 patients (100%)
      versus 50 of 59 patients (85%) who had this opinion regarding injections during
      their prior treatment cycles (p = 0.003). All 61 patients who stated a method of
      injection preference found the prefilled pen less stressful to use than syringes
      and would recommend the pen to another woman considering gonadotropin treatment.
      A total of 10/62 (16%) subjects reported 18 treatment-emergent adverse events
      (AEs). Two cases of ovarian hyperstimulation syndrome occurred post-treatment and
      one serious AE occurred (post-treatment ectopic pregnancy). Injection site
      reactions were generally mild to moderate, with mild itching (6 patients, 9.7%)
      and moderate redness in one patient. Fifteen patients reported mild redness
      (24.2%). Mild bruising (21.0%), mild pain (33.9%), and mild burning (32.3%) were
      also reported by patients. Seven patients (11.3%) had moderate pain. CONCLUSIONS:
      In this open-label, non-comparative study, patients undergoing OI preferred
      administering gonadotropins using the follitropin alfa prefilled pen compared to
      their prior use of vials/ampoules and a syringe. Patients using the prefilled pen
      found it less stressful, easier to use and more convenient than a conventional
      syringe and would recommend the pen to another woman considering gonadotropin
      treatment.

PMID- 17022859
TI  - Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in
      clinical trials for the treatment of respiratory infections.
AB  - OBJECTIVE: To compare safety data with levofloxacin 500 mg and 750 mg from
      clinical trials for the treatment of respiratory infections. METHODS: We compared
      adverse event data for levofloxacin 500 mg and 750 mg from clinical trials in
      acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis,
      and community-acquired pneumonia. Adverse events occurring after the initiation
      of therapy were classified as treatment-emergent adverse events (TEAE); drug
      related adverse events (DRAE) were TEAE assessed by the clinical investigator as
      definitely/very likely or probably related to levofloxacin therapy. RESULTS:
      Overall, the safety profile of the two doses was similar but not identical. TEAE
      occurred in 49.0% (1601/3268) of those treated with 500 mg and in 45.5%
      (519/1141) of those treated with 750 mg (p = 0.042); the corresponding rates of
      DRAE were 7.6% (248/3268) and 8.0% (91/1141) (p = 0.699). There was no
      statistically significant difference in terms of overall TEAE and DRAE rates
      within each of the three infectious conditions, but there were in specific
      events, all of which are expected with levofloxacin therapy. The limitations of
      this analysis include that it utilized a subset of available safety data, that it
      includes data only from clinical trials, and that we report primarily on events
      occurring in > or = 2% of patients. CONCLUSIONS: Given similar adverse event
      profiles and the advantages of higher dose therapy, including shorter courses of
      therapy and potential impact on preventing resistance, clinicians should consider
      utilizing the 750 mg dose of levofloxacin when choosing between dosage strengths
      for treatment of indicated infections.

PMID- 17022860
TI  - Exogenous endoscopy-related infections, pseudo-infections, and toxic reactions:
      clinical and economic burden.
AB  - OBJECTIVES: The objective of this study was to analyze the characteristics and
      costs of exogenous endoscopy-related infections, pseudo-infections, and toxic
      reactions in the US. METHODS: A systematic review of the scientific literature
      published between 1966 and 2005 was conducted in Medline. Data collection was
      based on a prospective protocol developed by the authors. RESULTS: The literature
      review included 70 outbreaks described in 64 scientific articles. Bronchoscopy
      accounted for half of all reported outbreaks. Inadequate decontamination
      practices were the leading cause of contamination; equipment malfunction became
      the second leading cause of contamination during the period 1990-2004. More than
      91% of the infections identified could be prevented by health care providers if
      quality control systems are improved and implemented. The available economic
      information concerning exogenous endoscope related events is very limited. A
      model for the analysis of the economic burden of exogenous endoscopy-related
      events is proposed. CONCLUSIONS: Proper decontamination practices, the use of
      protective sheaths, and the improvement of surveillance systems could reduce the
      clinical and economic burdens associated with exogenous endoscopy-related events.

PMID- 17022861
TI  - Preference for monthly darbepoetin alfa dosing in patients with chronic kidney
      disease not receiving dialysis.
AB  - OBJECTIVE: To determine patient preference for once-weekly Epoetin alfa versus
      once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD)
      not receiving dialysis. METHODS: AMPS (Aranesp Monthly Preference Study)
      consisted of two studies of similar design, each with a 2-week screening/baseline
      period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up
      period. Patients aged > or = 18 years had a nephrologist-reported diagnosis of
      CKD but were not receiving dialysis, and were required to have at least two
      hemoglobin levels within 10-12 g/dL and to have been receiving a stable dose (<
      25% change) of once-weekly or once-every-other-weekly Epoetin alfa for at least 8
      weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back
      to their previous Epoetin alfa regimen. The primary analysis assessed patient
      preference at week 21 for QM darbepoetin alfa versus previous once-weekly Epoetin
      alfa. RESULTS: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian,
      and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on
      study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161)
      preferred darbepoetin alfa QM, and of all patients who expressed a preference,
      regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM
      darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to
      mean hemoglobin at baseline (for those who completed the study and were receiving
      QM darbepoetin alfa at week 29: 11.2 [1.1] g/dL at week 29 versus 11.4 [0.7] g/dL
      at baseline). QM darbepoetin alfa was well tolerated. CONCLUSION: These data show
      that the majority of study patients preferred QM darbepoetin alfa to more
      frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels
      at week 29 and was well tolerated over the study period. The single-item
      questionnaire could be a potential limitation of this study and further
      investigation with a multi-question instrument may be helpful in confirming these
      results.

PMID- 17022862
TI  - Repetitive dihydroergotamine nasal spray for treatment of refractory headaches:
      an open-label pilot study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a repetitive intranasal (IN)
      dihydroergotamine (DHE) burst protocol for treatment of refractory headaches.
      RESEARCH DESIGN AND METHODS: Patients with refractory headaches were enrolled in
      a prospective, open-label, pilot study. Patients were instructed to self
      administer IN DHE every 8 hours for 3 days; each IN DHE dose consisted of one 0.5
      mg spray in each nostril that was repeated 15 minutes later, for a total of 2.0
      mg DHE per dose. Follow-up visits were scheduled approximately 3 weeks later.
      MAIN OUTCOME MEASURES: Efficacy and safety measurements were collected during
      patient interviews. Primary efficacy measures were the change in headache
      frequency, duration, and severity (rated from 0 [none] to 5 [extremely severe])
      between the initial and follow-up visits. Safety was assessed at the follow-up
      visits through the occurrence of adverse events (AEs). RESULTS: Twenty-six
      patients were enrolled in the study. Follow-up visits were completed by 24
      patients whose mean headache frequency at study entry was 6.6 d/wk. The IN DHE
      burst protocol was associated with significant mean decreases in headache
      frequency (2.6 d/wk, p < 0.001), duration (5.8 hours, p = 0.03), and severity
      (1.2 units, p < 0.001) between study entry and the follow-up visit. One patient
      discontinued IN DHE use early because of an AE (nasal stuffiness); two additional
      patients each reported one AE (fatigue and increased headache) that was
      attributed to IN DHE. CONCLUSIONS: The results of this pilot study suggest that
      the IN DHE burst protocol may be an effective and safe treatment for refractory
      headaches; interpretation of these results is limited by the open-label,
      uncontrolled design and the small number of patients. The development of a double
      blind, placebo-controlled study to further evaluate this treatment regimen is
      warranted.

PMID- 17022863
TI  - Ezetimibe/simvastatin single tablet versus rosuvastatin in patients with
      hypercholesterolemia.
AB  - Recent guidelines recommend strict goals for low density lipoprotein cholesterol
      (LDL-C) (70-100 mg/dL; 1.8-2.6 mmol/L). These goals were set following the
      publication of several trials. In the current issue of the journal, a study
      compares different doses of the combination tablet (ezetimibe/simvastatin) with
      statin monotherapy (rosuvastatin). In keeping with previous literature, the
      combination therapy was more effective in achieving LDL-C goals. This editorial
      comments on the potential disadvantages of using monotherapy with high-dose
      statins and considers the issue of statin-induced proteinuria. Combination
      therapy may need to be increasingly used to achieve the LDL-C targets set by
      recent guidelines.

PMID- 17022865
TI  - Economic implications of growth hormone use in patients with short bowel
      syndrome.
AB  - OBJECTIVE: Short bowel syndrome is a rare, life-threatening condition that can
      result in nutritional malabsorption. Parenteral nutrition provides life-saving
      support but can lead to complications and affect quality of life. Recombinant
      human growth hormone, somatropin (rDNA origin), has been shown to significantly
      reduce dependence on nutritional support (p < 0.05). This study evaluates the
      economic impact of somatropin use in the management of short bowel syndrome.
      METHODS: A discrete event simulation (DES) model was developed to estimate the
      benefits and costs associated with somatropin use. Risks of treatment
      complications and of disease-related events were modeled in identical patient
      pairs--one receiving parenteral nutrition alone, the other receiving 4 weeks of
      somatropin--for 2 years following initiation of treatment. Life expectancy was
      assumed equivalent. Risk functions were estimated from the literature and one
      randomized clinical trial. Total and component costs associated with each
      strategy were determined. The distribution of patients reducing parenteral
      nutrition need and the final parenteral nutrition frequency were also estimated.
      Sensitivity analyses were completed for key inputs. Direct medical costs are
      reported in US 2004 dollars. RESULTS: The model predicted that 96.0% of patients
      receiving somatropin reduce or eliminate parenteral nutrition within 6 weeks:
      average use was reduced by 2.8 days and one-third weaned completely. Based on 1.9
      L of parenteral nutrition per day, estimated costs were 118,098 dollars in year
      one and 132,935 dollars in year two. With somatropin, costs dropped to 84,309
      dollars in year one--despite the 17,459 dollars cost of somatropin treatment--and
      81,250 dollars in year two. Over 2 years savings totaled 85,474 dollars.
      LIMITATIONS: Insufficient data required that assumptions be made for some inputs.
      DES is new in pharmacoeconomics and may be perceived as a limitation.
      CONCLUSIONS: Somatropin use improves quality of life by reducing the need for
      parenteral nutrition and results in health care cost savings.

PMID- 17022864
TI  - Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus
      rosuvastatin in hypercholesterolemic patients.
AB  - OBJECTIVE: To assess the lipid-altering efficacy and safety of
      ezetimibe/simvastatin single tablet product compared with rosuvastatin at the
      approved usual starting, next highest, and maximum doses. RESEARCH DESIGN AND
      METHODS: Double-blind, multicenter, 6-week, parallel-group study in
      hypercholesterolemic patients (n = 2959). Patients were randomized based on
      stratification by low-density lipoprotein cholesterol (LDL-C) levels to
      ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20
      or 10 mg/day), the next highest (10/40 or 20 mg/day), and maximum doses (10/80 or
      40 mg/day). RESULTS: At all doses and across doses, ezetimibe/simvastatin reduced
      LDL-C levels significantly more (52-61%) than rosuvastatin (46-57%; p < or =
      0.001). Significantly greater percentages of all patients (p < 0.001) and high
      risk patients (p < or = 0.005) attained LDL-C levels < 70 mg/dL (1.8 mmol/L)
      following ezetimibe/simvastatin treatment compared with rosuvastatin at the
      prespecified doses and across doses. Ezetimibe/simvastatin also produced
      significantly greater reductions in total cholesterol (p < 0.001), non-high
      density lipoprotein cholesterol (p < 0.001), lipid ratios (p < or = 0.003), and
      apolipoprotein B (p < 0.05). Reductions in triglycerides were significantly
      greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (p =
      0.004) and next highest (p = 0.006) doses, and across all doses (p < 0.001).
      Increases in high-density lipoprotein cholesterol, and decreases in high
      sensitivity C reactive protein (hsCRP) were similar between treatment groups.
      Safety profiles were comparable for both treatments; however, the percent of
      patients with proteinuria was significantly higher following rosuvastatin
      treatment than ezetimibe/simvastatin, respectively at 10 mg versus 10/20 mg/day
      (p = 0.004) and 40 mg versus 10/80 mg/day (p < 0.001). CONCLUSION:
      Ezetimibe/simvastatin was more effective than rosuvastatin in LDL-C lowering, and
      provided greater or comparable improvements in other lipid measures and hsCRP at
      the approved usual starting, next highest, and maximum doses in
      hypercholesterolemic patients. Although the doses compared in this study were not
      equivalent on a milligram basis, the results provide clinically relevant
      information regarding the use of these drugs for initial therapy and for
      subsequent use at higher doses when appropriate. Both treatments were generally
      well-tolerated; however, this study was not powered nor of sufficient duration to
      assess the prevalence of rare clinical adverse effects. Overall,
      ezetimibe/simvastatin offers an effective and tolerable treatment option for
      lipid management. An assessment of its full clinical benefit awaits evaluation in
      longer-term clinical studies.

PMID- 17022867
TI  - Acute reactions to chemotherapy agents.
AB  - Acute reactions occur infrequently with chemotherapy agents. However, selected
      drugs have been known to be associated with severe hypersensitivity reactions,
      infusion reactions and other acute adverse events. The British Columbia Cancer
      Agency recently updated the list of selected drugs associated with
      hypersensitivity reactions and the minimum time that immediate physician coverage
      is needed.

PMID- 17022866
TI  - The effect of moxifloxacin on the normal human cornea.
AB  - OBJECTIVE: To investigate the effects of moxifloxacin on the cornea of normal
      human eyes using confocal microscopy and slit-lamp biomicroscopy. METHODS: This
      study enrolled adult volunteers who had a normal baseline ophthalmic examination.
      The dose regimen, similar to that of patients undergoing cataract extraction, was
      one drop of moxifloxacin in one eye four times a day for 3 days. The untreated
      fellow eye served as the control. Subjects had a baseline examination (Visit 1),
      started moxifloxacin the next day, and were examined 24 h (Visit 2) and 72 h
      (Visit 3) after starting medication. At each visit, visual acuity and adverse
      effects were recorded, slit-lamp examination with fluorescein was used to measure
      tear break-up time, and endothelial and epithelial cell counts were determined
      using confocal microscopy. RESULTS: Fifteen volunteers (mean age 37 +/- 7 years)
      enrolled. No significant difference in visual acuity, tear break-up time,
      endothelial or epithelial cell counts was noted between the treated and fellow
      eye. Subjects experienced no significant decrease in visual acuity, tear break-up
      time, or endothelial cell counts during the 3-day treatment period in either eye.
      Epithelial cell counts were stable at Visits 1 and 2, and decreased similarly in
      the treated and control eye at Visit 3. CONCLUSIONS: Moxifloxacin was safe for
      use during the 3-day treatment period. Moxifloxacin causes no significant
      epithelial or endothelial toxicity, and has no effect on visual acuity or ocular
      surface integrity in healthy subjects treated using a dosing regimen that
      simulated prophylactic use following cataract surgery.

PMID- 17022868
TI  - Management of hand-foot syndrome induced by capecitabine.
AB  - INTRODUCTION: Capecitabine (Xeloda) is a systemic prodrug of 5-fluorouracil (5
      FU), which is administered in an oral formulation. Hand-foot syndrome (HFS) has
      proven to be a chronic dose-limiting toxicity of capecitabine, leading to
      significant morbidity in patients receiving this agent. The purpose of this
      review is to define the pathophysiology, risk factors, incidence and management
      of capecitabine-induced HFS. METHODS: Literature for this review article was
      collected from the following databases: PubMed, CINAHL, and the proceedings of
      the American Society of Clinical Oncology (ASCO) confined to the years 1995-2006.
      The following key terms were used in the search: hand-foot syndrome, palmar
      plantar erythrodysesthesia, capecitabine, Xeloda, colorectal cancer, and
      metastatic breast cancer. RESULTS: HFS associated with capecitabine is a serious
      dose-limiting toxicity. Incidence of grade 3/4 toxicity is of extreme
      significance, and introduces the need for dose reductions and/or interruptions in
      capecitabine therapy. Drug-related therapies studied include topical emollients
      and creams, systemic and topical corticosteroids, nicotine patch, vitamin E,
      pyridoxine, and COX-2 inhibitors. However, due to the lack of randomized,
      controlled trials with these therapies, the current mainstay of treatment for the
      management of this toxicity is interruption of therapy and, if necessary, dose
      reduction. CONCLUSION: Treatment interruption or dose reduction remain the only
      methods shown to effectively manage HFS, but supportive measures to reduce pain
      and discomfort and prevent secondary infection are very important. Many other
      prophylactic and treatment strategies have been investigated, with pyridoxine and
      COX-2 inhibitors being the most promising in case reports and retrospective
      studies; therefore, prospective, randomized, controlled trials are needed to
      prove their efficacy.

PMID- 17022869
TI  - Evaluation of vaccine dosing in patients with solid tumors receiving
      myelosuppressive chemotherapy.
AB  - OBJECTIVE: To provide oncology healthcare providers with information on current
      vaccine recommendations and discuss the proper timing of vaccination in relation
      to chemotherapy, to allow for an adequate, protective antibody response. DATA
      SOURCES: In this review, we have attempted to include all available literature as
      well as the current recommendations. The National Library of Medicine, PubMed
      online database was searched using the keywords: chemotherapy, influenza,
      vaccine, cancer, immunosuppression. In addition, the Center for Disease Control
      (CDC) guidelines were reviewed and incorporated into the recommendations. DATA
      SYNTHESIS: There were several limitations to the literature available. To date,
      most of the literature was completed in the 1970s and 1980s, and definitions of
      protective immunity regarding influenza vaccines have changed over time, as well
      as improved study design. These studies have also been completed in a variety of
      disease states, hence, it is difficult to make comparisons between trials. The
      recommendations in this review are consistent with the current CDC Guidelines
      and, until further clinical trials are carried out, are the most conservative
      recommendations in favor of patient safety, health care costs, and resource
      utilization. CONCLUSION: Patients on cancer chemotherapy should receive
      vaccination at least 2 weeks before initiation of treatment. Providers should
      avoid administering vaccination during chemotherapy or active radiation treatment
      because of suboptimal responses to vaccines. Active immunization has been shown
      to confer protective immunity to several infections in cancer patients at similar
      rates to healthy individuals.

PMID- 17022870
TI  - Fatigue in cancer patients treated with cytotoxic drugs.
AB  - STUDY OBJECTIVES: Cancer-related fatigue is a significant and distressing problem
      for the cancer patient, affecting their physical and psychosocial function
      negatively, and reducing their quality of life. The aims of this study were to
      assess frequency, severity, and the consequence of fatigue in cancer outpatients
      receiving cytotoxic drugs, using an existing international fatigue scale applied
      for Swedish use. METHODS: The study used a non-randomized, prospective design to
      evaluate fatigue and its impact on quality of life in outpatients receiving
      cytotoxic drugs. Once a week, 147 cancer patients, in an outpatient ward for
      cytotoxic drug administration, filled out questionnaires containing 13 items from
      the Fatigue Symptom Inventory (FSI), and five additional questions. RESULTS:
      Prevalence of fatigue was 92% in the week after all patients had received
      cytotoxic drugs, and patients were statistically significantly more fatigued
      during than before treatment. The degree of fatigue was highest the week after
      treatment, and declined over the following week. Other symptoms, especially
      depressed mood, showed a strong correlation with cancer and cytotoxic-induced
      fatigue. Lung and breast cancer patients experienced the highest degree of
      fatigue. Some cytotoxic drug regimens were, apart from the underlying disease,
      associated with high fatigue scores, eg, those with cyclophosphamide or
      gemcitabine. Patients not receiving first line treatment scored significantly
      higher fatigue with more influence on daily living. CONCLUSION: The study
      verified that fatigue is a common side effect, and affects quality of life
      negatively, even for outpatients receiving cytotoxic drugs. The clinical oncology
      pharmacist must inform patients that a severe tiredness, fatigue, may follow
      cytotoxic drug administration.

PMID- 17022871
TI  - Dose conversion and cost effectiveness of erythropoietic therapies in
      chemotherapy-related anemia: a Canadian application.
AB  - OBJECTIVE: To determine the dose-conversion ratio (DCR) between epoetin alfa and
      darb-epoetin alfa in cancer patients and compare the treatment costs of both
      agents at the estimated DCRs. METHODS: A comprehensive search of the literature
      was carried out on clinical trials evaluating patients with chemotherapy-related
      anemia treated with epoetin alfa or darbepoetin alfa. A multivariate meta
      analysis regression was conducted to determine the relative doses of these two
      agents at which they were equally effective. The effectiveness measure used was
      the area under the hemoglobin change curve. Using the estimated DCR for each
      dosing regimen, the relative cost of epoetin alfa and darbepoetin alfa treatments
      in Canada was evaluated. RESULTS: Twenty-nine study arms, evaluating 12,923
      patients (10,582 treated with epoetin alfa and 2341 treated with darbepoetin
      alfa), were eligible for this study. Results comparing specific dosing regimens
      indicated that the DCRs were systematically lower than 200:1. The cost premium
      associated with darbepoetin alfa weekly drug cost was between 37 and 44% above
      epoetin alfa for the same level of effectiveness. CONCLUSION: Based on the
      evidence from this meta-analysis, epoetin alfa appeared to be more cost-effective
      compared to darbepoetin alfa in Canada for cancer patients.

PMID- 17022872
TI  - Development of daptomycin resistance in a bone marrow transplant patient with
      vancomycin-resistant Enterococcus durans.
AB  - Daptomycin has demonstrated antibacterial activity against several antibiotic
      resistant strains, including vancomycin-resistant enterococci. A paucity of data
      exists concerning in vivo development of daptomycin resistance of enterococci. We
      describe an allogeneic bone marrow transplant patient, who was found to have
      vancomycin-resistant Enterococcus durans bacteremia, which subsequently developed
      resistance to daptomycin.

PMID- 17022873
TI  - A few thoughts on reflective testing.

PMID- 17022874
TI  - Cardiovascular disease prevention: the new Joint British Societies' guidelines.
AB  - The Joint British Societies' recommendations for coronary heart disease (CHD)
      prevention have been updated in the light of recent developments. Key features of
      the new guidelines include focusing on cardiovascular disease (CVD) prevention
      rather than CHD and adopting strategies that target high-risk groups, with equal
      priority being given to all those with established CVD or diabetes mellitus.
      Subjects without CVD but with a risk factor profile resulting in an absolute risk
      of developing CVD>or=20% over 10 years should be included in these strategies and
      CVD prevention should also be applied to subjects with particularly unfavourable
      single risk factors including familial dyslipidaemias, such as familial
      hypercholesterolaemia, hypercholesterolaemia when the total cholesterol:HDL
      cholesterol ratio is >or=7.0, hypertension when the blood pressure (BP)>or=160
      mmHg systolic or >or=100 mmHg diastolic or lesser degrees of hypertension when
      there is end-organ damage. The optimal target for total cholesterol is <4.0
      mmol/L and for LDL cholesterol<2.0 mmol/L, or a reduction of 25% in total
      cholesterol and a 30% reduction in LDL cholesterol, whichever achieves the lower
      absolute level. The optimal BP target is <140 mmHg systolic and <85 mmHg
      diastolic pressure with lower targets in subjects with CVD, diabetes or chronic
      renal failure. If these conditions are present, treatment should aim to achieve
      <130 mmHg systolic and <80 mmHg diastolic pressures.

PMID- 17022875
TI  - Gilbert's syndrome: an overview for clinical biochemists.
AB  - Gilbert's syndrome (GS) is a benign and inherited state characterized by mild,
      lifelong, unconjugated hyperbilirubinaemia in the absence of haemolysis or
      evidence of liver disease. Its molecular basis, mutations in the TATA box
      upstream of the uridine diphosphoglucose glucuronyltransferase gene, leads to
      impaired bilirubin glucuronidation. This synopsis outlines the pathophysiology
      and investigation appropriate for this innocent anomaly.

PMID- 17022876
TI  - Human circadian rhythms: physiological and therapeutic relevance of light and
      melatonin.
AB  - Ocular light plays a key role in human physiology by transmitting time of day
      information. The production of the pineal gland hormone melatonin is under the
      control of the light-dark cycle. Its profile of secretion defines biological
      night and it has been called the 'darkness hormone'. Light mediates a number of
      non-visual responses, such as phase shifting the internal circadian clock,
      increasing alertness, heart rate and pupil constriction. Both exogenous melatonin
      and light, if appropriately timed, can phase shift the human circadian system.
      These 'chronobiotic' effects of light and melatonin have been used successfully
      to alleviate and correct circadian rhythm disorders, such as those experienced
      following travel across time zones, in night shift work and in circadian sleep
      disorders. The effectiveness of melatonin and light are currently being optimized
      in terms of time of administration, light intensity, duration and wavelength, and
      melatonin dose and formulation. The aim of this review is not to replicate
      information that has been reported in a number of reviews of the human circadian
      timing system and the role of melatonin and light, but rather to extract findings
      relevant to the field of clinical biochemistry.

PMID- 17022877
TI  - Reflective testing--what do our service users think?
AB  - BACKGROUND: Reflective testing incorporates the clinical judgement, knowledge and
      experience of an individual biochemist to request additional tests appropriate to
      the clinical scenario. Despite being vigorously debated within the biochemistry
      profession, little is known about how the clinicians directly involved in patient
      care feel about it. We have conducted a survey to elicit our service users'
      opinion of reflective testing. METHODS: Ten clinical scenarios, each involving
      the possible addition of a specific test, were circulated to 520 hospital doctors
      and 152 general practitioners. The four response options were to add further
      tests, phone and discuss the case, add a comment to the original results or do
      nothing. RESULTS: A total of 216 (32%) responses were received. Overall, the
      majority were in favour of 'adding on' free triiodothyronine (86%), gamma
      glutamyltransferase (78%), lipid profile (59%), thyroid peroxidase antibodies
      (63%), pituitary hormones (58%), troponin (55%) and serum electrophoresis (68%)
      in the given scenarios. However, only 30% would like a pregnancy test added and
      only 45% a prostate-specific antigen added without prior consultation. The
      response differed according to grade and specialty. CONCLUSIONS: Reflective
      testing is generally welcomed by our service users, provided the nature and
      implications of the specific test is considered in addition to the full clinical
      scenario.

PMID- 17022878
TI  - Reflective testing: what do patients think?
AB  - INTRODUCTION: Reflective testing refers to the practice of adding on tests by
      laboratory staff. Little is known about what patients think of this practice.
      METHODS: We surveyed patients attending a general practice surgery and patients
      attending hospital outpatient clinics. We sought their views about the practice
      of adding on tests and about the information they received from requesting
      clinicians about their investigations. RESULTS: In both groups of patients, large
      majorities favoured an approach in which relevant additional tests are performed
      without consulting the requesting clinician or patient first. Most patients also
      felt that the requesting clinicians had provided a satisfactory explanation about
      what tests were to be performed and why. CONCLUSION: Most patients are content to
      let NHS professionals add on relevant tests if this is felt to be in their
      interest.

PMID- 17022879
TI  - Outcomes of discretionary laboratory requesting of serum protein electrophoresis.
AB  - BACKGROUND: Discretionary laboratory requesting of serum protein electrophoresis
      (SPE) is widespread throughout the UK despite limited evidence to support
      clinical usefulness. We aimed to examine the clinical usefulness of discretionary
      SPE requesting on serum samples with globulins>45 g/L by documenting the number
      of discretionary tests performed and the number of paraproteins identified in an
      audit period, by determining if such findings led to further
      investigation/specialty referral, and by identifying the final diagnosis and
      subsequent management of these patients. METHODS: A retrospective one-year audit
      from July 2002 to June 2003 was carried out using information from biochemistry
      databases and review of medical records. RESULTS: Of 1332 discretionary SPEs
      performed in one year, 72 paraproteins were identified (5.4%). Further clinical
      information could be obtained in 66 cases. Appropriate follow-up occurred in 84%
      of cases. The most common diagnosis was monoclonal gammopathy of undetermined
      significance (56%). Eighteen percent of patients with an identified paraprotein
      were diagnosed with B-cell malignancies that warranted treatment. A further 6%
      progressed to requiring treatment during follow-up. CONCLUSION: Using screening
      criteria of serum globulins>45 g/L, one in 20 discretionary laboratory requests
      resulted in a clinically relevant finding. These results suggest such requesting
      is worthwhile and should aid future debate on the appropriateness of this
      practice.

PMID- 17022880
TI  - The evaluation of a novel conductometric device for the diagnosis of cystic
      fibrosis.
AB  - BACKGROUND: We evaluated the diagnostic discrimination of a new micro-flow cell
      device (Nanoduct) which measures sweat conductivity in situ at a regional
      referral centre for cystic fibrosis (CF). METHODS: The device was evaluated in
      comparison to the measurement of sweat chloride with the established quantitative
      pilocarpine iontophoresis test (QPIT) and extended in a number of patients to
      conductivity measurements in liquid sweat collected with the Macroduct system.
      Sweat testing was conducted simultaneously on patients referred for diagnostic
      sweat testing, on patients known to have CF and on adult volunteers. The intra
      individual variability, the failure rate and diagnostic accuracy were determined.
      RESULTS: A total of 110 tests were performed on 100 individuals, 36 of whom had
      classical CF and six of whom had non-classical CF. The Nanoduct system produced a
      false negative result in one quarter of the patients with classical CF. Moreover,
      conductivity was negatively biased compared with chloride in this group. Repeat
      testing of the false negatives using a new batch of sensors and/or measuring
      conductivity in liquid sweat collected with the Macroduct device gave accurate
      diagnostic discrimination indicating that the original sensors were faulty.
      Photographic examination confirmed that a batch of sensors were defective.
      CONCLUSIONS: Our experience suggests that the prototype microflow cell
      conductometric device cannot be used for the diagnosis of CF due to the high
      false negative rate. As a consequence of this study, the manufacturers have
      implemented a pre-testing system to quality control the sensors prior to issue.

PMID- 17022881
TI  - The measurement of whole blood pre-treatment cyclosporine A: metabolite ratios
      predicts the onset of renal dysfunction in recipients of allogeneic stem cell
      transplantation.
AB  - BACKGROUND: In the context of post-transplant immunosuppression, cyclosporine A
      (CSA) is dose adjusted in accordance with whole blood drug monitoring. While
      currently available immunoassay systems primarily target the parent drug, cross
      reactivity results in the detection of the major circulating CSA metabolites,
      though their contribution to both immunosuppression and toxicity remain unclear.
      This study examines the relationship of CSA metabolites to hepatic and renal
      dysfunction and the incidence of graft-versus-host disease (GvHD) through
      parallel assaying of parent drug and drug/metabolites expressed as a metabolite
      ratio (Cp:mR). METHOD: Sequential pre-treatment (trough) whole blood samples
      (n=527) were collected from 31 allo-stem cell transplantation (SCT) recipients.
      Both parent drug and drug/metabolite levels were determined using the Abbott
      fluorescence polarization immunoassay. RESULTS: The average mean Cp:mR was
      significantly higher in patients with hepatic (P=0.004) and renal dysfunction
      (P=0.004) than in those without. Significantly higher Cp:mR were also found in
      patients with grades II-IV GvHD (P=0.001) than were observed in patients who did
      not experience significant GvHD. When measured prospectively, an increasing Cp:mR
      predated the rise in serum creatinine concentration by a median of two weeks.
      CONCLUSIONS: This study demonstrates a clinically useful CSA metabolite ratio
      that shows association with hepatic and renal dysfunction and with GvHD. The
      measure can be used to predict those patients on CSA therapy who are likely to
      develop renal dysfunction.

PMID- 17022882
TI  - Determining urinary calcium/creatinine cut-offs for the paediatric population
      using published data.
AB  - BACKGROUND: The purpose of this study was to determine a cut-off above which a
      result is considered abnormal for 'spot' calcium-to-creatinine ratio (Ca/Cr) in
      urine in the paediatric age group. While the cut-offs are not well established,
      there are many published reports of urine Ca/Cr excretion ratio in the
      literature. Rather than undertaking a difficult, time-consuming, expensive, and
      ultimately redundant study, an analysis of these published works was undertaken
      to determine urine Ca/Cr cut-offs for the laboratory. METHODS: Fourteen studies
      reporting urine Ca/Cr ratio available in the literature were reviewed. Each study
      was abstracted for several characteristics. The data were plotted and the line of
      best fit describing the data was determined. Using the function describing the
      line, cut-offs by pertinent age were recalculated. These cut-offs were then
      compared to the original data and to in-house data. RESULTS: The function
      describing the line of best fit was y=-0.3175 ln(x) +1.46 (y=Ca/Cr in mmol/mmol
      and x=age in years), r2=0.85. After consultation with the paediatric
      nephrologists and comparison with our in-house data, cut-offs for age groups of
      <1, 1-<2, 2-<5, 5-<10, and 10-18 years in mmol/mmol of 1.50, 1.25, 1.00, 0.70,
      and 0.60, respectively, were derived. CONCLUSIONS: Using data from 14 published
      studies, suitable spot urine Ca/Cr cut-offs from birth to 18 years of age were
      determined.

PMID- 17022883
TI  - Urine free cortisol analysis by automated immunoassay and high-performance liquid
      chromatography for the investigation of Cushing's syndrome.
AB  - BACKGROUND: We compared a widely used immunoassay method for urine free
      corticoids with a high-performance liquid chromatography (HPLC) method for the
      investigation of Cushing's syndrome. METHODS: Urine free corticoid analysis using
      an Immulite:2000 automated immunoassay analyser and urine free cortisol analysis
      by a specific HPLC method on 39 patients with an elevated baseline immunoassay 24
      h urine free corticoid result who were referred from 2000 to 2004. RESULTS:
      Reference ranges for urine free corticoids by immunoassay and for urine free
      cortisol by HPLC were <900 and <170 nmol/day, respectively. Of the 39 patients
      with an elevated immunoassay urine free corticoid result, Cushing's syndrome was
      surgically proven in 22 patients, giving a positive predictive value of 56%.
      Cushing's syndrome was excluded in 12 of the remaining 17 patients by applying
      the specific HPLC method and at least one of the following: a clinical evaluation
      which was not suggestive or adequate suppression of plasma cortisol following
      dexamethasone. Urine free cortisol analysis by HPLC gave a positive predictive
      value of 81% for Cushing's syndrome. CONCLUSIONS: Although immunoassay has a low
      specificity for urine cortisol, it is a widely available test which serves as a
      valid initial investigation of Cushing's syndrome.

PMID- 17022884
TI  - Evaluation of four portable self-monitoring blood glucose meters.
AB  - Self-monitoring of blood glucose (SMBG) is a cornerstone of diabetes care.
      However, the effectiveness of any glucose-monitoring programme depends on the
      ability to integrate SMBG into a program of self-care and therapeutic decision
      making. Because the accuracy of SMBG is instrument dependent, we analysed 45
      heparinized whole blood specimens using four marketed portable glucose meters to
      evaluate whether their precision and accuracy would be efficient and safe for
      clinical use. All measurements were standardized and performed by a single expert
      health-care professional at the same clinical chemistry laboratory. Results were
      compared with those obtained on the same plasma samples by the hexokinase method
      on a secondary reference analyser and further analysed according to the error
      tolerance criteria and the current American Diabetes Association (ADA), Clinical
      Laboratory Improvement Amendments (CLIA), and National Committee for Clinical
      Laboratory Standards (NCCLS) guidelines. The within-run imprecision ranged from
      2.2% to 3.2%. Passing and Bablok regression analysis yielded slope values from
      0.93 to 1.07 and correlation coefficients between 0.994 and 0.998. When compared
      with the secondary reference analyser, mean variations were between -4.9% and
      14.1%, fulfilling in three out of four cases the 5.5% current desirable
      analytical quality specifications for total error. Nevertheless, when considering
      the two standard deviations level of this bias, several results exceeded this
      limit. Although three out of four devices tested achieved or came closer to the
      NCCLS C30-A2, CLIA and error tolerance targets, none of them met the current
      analytical ADA thresholds. Despite the acceptable analytical performances, we
      demonstrated that standardization and harmonization of results in SMBG have not
      been fully achieved.

PMID- 17022885
TI  - Acute intermittent porphyria associated with hyperthyroidism.
AB  - The differential diagnosis of abdominal pain with associated hyponatraemia should
      include acute intermittent porphyria. Development of hyperthyroidism in a patient
      with latent porphyria may precipitate an acute attack and increase disease
      severity. Treatment of hyperthyroidism may prevent recurrent episodes.

PMID- 17022886
TI  - Interpretation of the short Synacthen test in the presence of low cortisol
      binding globulin: two case reports.
AB  - CONTEXT: Ten percent of serum total cortisol (TC) is unbound; the remainder is
      bound to cortisol-binding globulin (CBG) and, to a lesser extent, albumin. CBG
      concentrations can drop significantly, particularly in critical illness,
      resulting in a low TC although the free, active, cortisol may be normal or
      increased. In the context of a low CBG, the diagnosis of pituitary-adrenal
      insufficiency with measurements of TC is difficult. OBJECTIVE: To remind
      clinicians of the difficulty in interpreting TC when the CBG is low, the
      circumstances when CBG concentrations may decrease and that measurement of CBG
      and calculation of the free cortisol index can help in the assessment of
      pituitary-adrenal reserve. CASE: We present two patients at risk of primary and
      secondary adrenal insufficiency with a poor response to 250 microg Synacthen. In
      both cases we confirmed low CBG concentrations but a normal free cortisol index
      (FCI), confirming normal pituitary-adrenal reserve. INTERVENTION: In case one, we
      have been able to avoid long-term steroid replacement therapy. We continue to
      reduce the steroid dose in case 2 but have been limited by the need for high-dose
      steroid treatment for exacerbations of the patient's airways disease. CONCLUSION:
      The use of TC in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis
      may give rise to misleading results if the CBG concentration is low. The FCI may
      be a better marker of pituitary-adrenal reserve in these subjects. Clinicians
      should be cautious when interpreting abnormal cortisol results and we emphasize
      the importance of good clinical assessment.

PMID- 17022887
TI  - Differences of prostate-specific antigen assays: a small light at the end of the
      tunnel?

PMID- 17022888
TI  - Accuracy assessment of PSA methods must be based on clinical instead of
      artificial samples--a response to AW Roddam et al., Ann Clin Biochem 2006; 43: 35
      48.

PMID- 17022891
TI  - [Critical medicine in obstetrics: a new specialty].

PMID- 17022892
TI  - [Laryngeal cancer in patients younger than 40 years].
AB  - BACKGROUND: We undertook this study to report demographic data of laryngeal
      cancer patients <40 years old and treatment results. METHODS: In a retrolective
      study we reviewed the clinical records of 500 patients with laryngeal cancer in
      the period from 1989 to 2004 and included those patients<40 years of age.
      RESULTS: We found 15 patients, representing 4.4% of the series. Nine (60%) were
      men and six (40%) were women, with a 1.5:1 ratio. Average group age was 35 years
      (range 21-40 and median of 37 months). Average time of evolution at the time of
      diagnosis was 14.4 months (range 0-36 and median of 12 months); 60% of the
      patients were smokers and 40% admitted to drinking alcohol; dysphonia was the
      main symptom found in 87% of the patients. The most frequent location was the
      glottis in 11 (73%) patients. Well-differentiated tumors represented 53% of the
      cases. Initial treatment was surgery in four (27%) patients; radiotherapy in five
      (33%) patients receiving an average of 63.44 Gy; concomitant chemoradiotherapy in
      one patient (7%) using gemcitabine; four (27%) patients were treated with
      neoadjuvant chemotherapy followed by radiotherapy; and one patient did not
      receive treatment. The average time in which the patients relapsed after the
      first treatment was 19.57 months (range 2-63) and four were classified as
      persistent. Survival time was 32 months (range 2-106 and median 27 months).
      Finally, organ preservation rate was obtained in 28.5%. CONCLUSIONS: Squamous
      cell carcinoma of the larynx is rare in patients<40 years old in our study.
      Gender relation seems to be equal, although a slight predominance of men does
      still exist. Classical risk factors were present in 60% of the cases. Prognosis
      for these patients was determined by the initial clinical stage.

PMID- 17022893
TI  - [Qualitative determination of markers for myocardiac necrosis during pre-hospital
      admission for acute coronary syndrome].
AB  - OBJECTIVE: We measured the diagnostic value of troponin I (TnI), mioglobin (Miog)
      and creatine kinase MB (CPK-MB) in patients with thoracic pain during the period
      of preadmission to the hospital. METHODS: We included patients who requested
      prehospital attention with intensive therapy ambulance or who were in the first
      hours of hospitalization for thoracic pain. A 12-lead electrocardiogram was
      carried out in the ambulance or in the emergency room. The levels of total
      creatine phosphokinase were determined (as reference pattern). Five study groups
      were included: group I, 13 patients with acute myocardial infarction without
      elevation of the ST segment; group II, 11 patients with unstable angina; group
      III, 14 patients with atypical thoracic pain for angina; group IV, five healthy
      patients; and group V, five patients with acute myocardial infarction with
      elevation of the ST segment. A qualitative evaluation was made with an automatic
      device for quick interpretation of TnI, Miog and CPK-MB. RESULTS: Forty eight
      patients were studied with an average age of 55+/-18 years, 25 men (52%) and 23
      women (48%), average time of symptom evolution was 3.5 h (quartiles 2 and 6 h).
      Total level of CPK was taken as a reference pattern. Sensitivity of TnI, Miog,
      and CPK-MB was 100%, specificity was 94, 91 and 94%, respectively. Positive
      predictive value was 89, 84 and 89%, respectively. Negative predictive value was
      100%. Likelihood of probability was 8.7, 5.5 and 8.7, respectively. CONCLUSIONS:
      TnI, Miog and CPK-MB have high diagnostic value in acute coronary syndrome (ACS)
      from the time of prehospital admission. Determination is advisable as part of the
      diagnostic protocol, which is of great importance in order to plan the
      hospitalization and treatment in this group of patients.

PMID- 17022894
TI  - [Withdrawal of chest tubes without water seal vs. negative continuous suction
      after closed cardiovascular surgery procedures in children].
AB  - BACKGROUND: We undertook this study to compare the frequency and type of
      complications, as well as the length of hospital stay, in children who underwent
      closed cardiovascular surgery with chest tube drainage during the postsurgical
      period with children in whom the drainage was withdrawn with continuous suction,
      once thoracotomy was completed. METHODS: A retrospective, descriptive and
      analytic study was performed at the IMSS Hospital de Pediatria, located at the
      XXI Century National Medical Center in Mexico City. Eighty eight children who
      underwent closed cardiovascular surgery (Group I) without chest tubes and 42 with
      chest tubes (Group II) were studied. RESULTS: In Group I the frequency of
      complications was 27.3% and in group II 59.5%. Complications were as follows:
      subcutaneous emphysema was seen in 13.6% (n=12) of group I and in 45.2% (n=19) of
      group II (p=0.0001); pneumothorax in 13.6% (n=12) vs. 28.6% (n=12), p=0.04; and
      chylothorax in 2.3% (n=2) vs. 2.4% (n=1), p=1.0, respectively. The median time of
      hospital stay in group I was 3 days and in group II was 6 days (p=0.0001).
      CONCLUSIONS: In children, in some closed cardiovascular surgeries, withdrawal of
      chest tube drainage with negative suction when thoracotomy is completed may
      decrease the frequency of pneumothorax, subcutaneous emphysema and length of
      hospital stay, in comparison with patients in whom chest tube drainage is left
      during the postoperative period.

PMID- 17022895
TI  - [Mean airway pressure during pressure-controlled ventilation with static vs.
      dynamic positive end-expiratory pressure].
AB  - BACKGROUND: Positive end-expiratory pressure increases mean airway pressure (Paw)
      in patients with mechanical ventilation. We undertook this study to compare mean
      airway pressure (Paw) generated with static PEEP (sPEEP) vs. dynamic PEEP (dPEEP)
      at the same level of total PEEP (tPEEP) in the same patient with pressure
      controlled mechanical ventilation (PC). METHODS: We conducted a prospective
      clinical trial at the Intensive Care Unit of a university-affiliated hospital.
      Consecutive patients in PC with SaO2>90%; FiO2<50%; sPEEP of 4 cm H2O and
      inspiration-expiration ratio (I:E ratio) 1:2 were included in the study. After a
      basal period of time of 15 min, Paw was registered (phase one of the study
      protocol). In phase 2 with the ventilator settings constant, only the I:E ratio
      was switched to 2:1 to generate dPEEP, and after 15 min Paw and total PEEP
      (tPEEP) were registered (tPEEP=sPEEP+dPEEP). In phase 3, the I:E ratio was
      switched back to 1:2 substituting the dPEEP generated in the second phase of the
      study by sPEEP to maintain the same level of tPEEP of phase 2. After 15 min, Paw
      was again registered. Friedman and Wilcoxon's test were used, p value<0.05 was
      considered statistically significant. RESULTS: Thirty eight patients were
      admitted to the study protocol, tPEEP was 4, 8 and 8 cm H2O and median of the Paw
      8.7, 13.8, and 11.4 cm H2O, respectively, with a p value<0.05 in the first,
      second and third phases of the study. CONCLUSIONS: During pressure control
      ventilation, mean airway pressure is affected by the level of total PEEP and its
      composition. Paw is higher when dynamic PEEP participates in the composition of
      total PEEP.

PMID- 17022896
TI  - [Hidradenitis suppurativa].
AB  - BACKGROUND: Hidradenitis suppurativa is an inflammatory, chronic and recurrent
      disease of appocrine glands, located in inguinal, axillar, perineal, perianal
      areas and scalp. OBJECTIVE: To determine the frequency and therapeutic
      management. METHODS: A retrospective, transverse, and descriptive study was
      carried out. All patients with hidradenitis suppurativa, and who were managed by
      the Coloproctology Unit from the Gastroenterology Service of the General Hospital
      of Mexico City from January 1995 to December 2004, were included. RESULTS: We
      reviewed 12,689 files and identified 15 patients (0.12%) with hidradenitis
      suppurativa; nine fulfilled inclusion criteria. CONCLUSIONS: This is a complex
      disease with a diagnostic and therapeutic challenge.

PMID- 17022897
TI  - [Dyspareunia after total abdominal hysterectomy. Anatomical relation].
AB  - BACKGROUND: We undertook this study to determine whether anatomic changes after
      total abdominal hysterectomy are a cause of dyspareunia in premenopausal women.
      METHODS: This is a comparative, prospective and longitudinal study in 50
      premenopausal women with benign uterine disease without dyspareunia treated with
      total abdominal hysterectomy. Primary variable was presence of postsurgical
      dyspareunia. Secondary variables are presurgical and assessment 3 months after
      surgery of left, right, anterior and posterior vaginal longitude (VLL, VRL, VAL
      and VPL, respectively) expressed in centimeters, as well as of the vaginal volume
      (VV). Statistical analysis for mean, central tendency and t-test. Group 1 (G1) is
      comprised of patients with postsurgical dyspareunia and Group 2 (G2) is comprised
      of patients without dyspareunia. RESULTS: In G1, three patients (mean age: 42
      years) had dyspareunia, pre- and postsurgical mean values were VV 146.6 and 100,
      VLL 8 and 7.3, VPL 9.16 and 7.3, VLL 8 and 7.3, VRL 8 and 7.3. In G2, 47 patients
      (mean age: 40.36 years) were without dyspareunia, pre- and postsurgical values
      were VV 150.6 and 121.57, VLL 8.81 and 8.12, VPL 9.7 and 8.69, VLL 9.24 and 8.3,
      VRL 9.28 and 8.33. We did not find significant differences between the groups.
      Two of the three patients with dyspareunia had a vaginal granuloma, but the third
      case did not show an anatomical cause. CONCLUSIONS: There is no relationship
      between total abdominal hysterectomy in premenopausal women and anatomical
      vaginal changes after surgery as assessed by vaginal volume and longitude.
      Presence of vaginal granuloma was responsible for dyspareunia in 4% of cases.
      Dyspareunia was found in 2% of premenopausal women without posthysterectomy
      anatomical cause.

PMID- 17022898
TI  - [Biosimulator training and its impact on skill in laparoscopic cholecystectomy].
AB  - OBJECTIVE: We undertook this study to determinate the educational impact of
      training in an inanimate biosimulator in terms of effectiveness, time and
      complications in performing laparoscopic cholecystectomy. METHODS: We used a
      comparative, experimental cohort, prospective and longitudinal. Three first
      postgraduate-year residents and one pre-grade internship physician were trained
      and assessed in basic laparoscopic skills using a biosimulator (fiberglass
      "dummy" where animal organs are introduced ex-vivo). The participants acted as
      their own control, performing a procedure to determine surgical time,
      complications and effectiveness. Later they observed a short video demonstrating
      the suitable development of laparoscopic cholecystectomy. The video defined the
      specific deviations from the ideal cholecystectomy, which were considered as
      errors. Every procedure was videotaped, beginning with the careful dissection of
      cystic structures and clipping them, continuing with the dissection of the
      gallbladder from the liver with the standardized method. Each participant
      performed ten procedures. RESULTS: There were no differences in baseline
      assessment of basic skills. All participants completed all proposed procedures.
      Surgical time was 61% faster at the end of the study (p<0.001), as well as
      demonstrating a lower rate of complications of 0.67% (p<0.009). CONCLUSIONS:
      Skills training in endoscopic surgery by means of an inanimate biosimulator is
      superior to traditional training because it decreases surgical time and surgical
      complications without ethical considerations and the effect of a learning curve
      in the operating room.

PMID- 17022899
TI  - [Fibromatosis infantile. Report of an aggressive disease].
AB  - This rare entity is characterized by multiple nodular lesions largely composed of
      collagen-forming spindle cells and involving the subcutis, skeletal muscle, bone
      and viscera of newborns and infants that occurs in either a solitary or
      multicentric form. The clinical course of a case is presented. The patient is a 2
      year-old male who was brought to our hospital because of a large cervical mass.
      On physical examination a firm, subcutaneous, immobile painless mass measuring
      4.5x6 cm was palpated at right side of neck. After the first admission, 13
      complete surgical resections were performed. This patient is the eleventh
      familial case in the literature. The patient died 10 years after the first
      surgery.

PMID- 17022900
TI  - [Appendiceal mucocele and gangrenous cholecystitis].
AB  - OBJECTIVE: We present a case report of appendiceal mucocele and gangrenous
      cholecystitis. SETTING: Hospital de Especialidades, Centro Medico Nacional Siglo
      XXI, Mexico, D.F. CLINICAL CASE: An 80-year-old man was admitted to the hospital
      with diagnosis of acute cholecystitis and abdominal tumor under study, with
      complaints of abdominal pain for 10 days located in the right upper quadrant,
      without fever or significant weight loss. Laboratory analyses revealed moderate
      leucocytosis. CT of the abdomen revealed thickening of the gallbladder wall and
      acute local inflammation, as well as the presence of abdominal tumor in the right
      lower quadrant. The patient was surgically explored with the following findings:
      gangrenous cholecystitis and appendiceal tumor of 20 cm length. Cholecystectomy
      and appendectomy was performed. The postoperative period was normal. The final
      histological report was appendiceal mucocele and the patient was discharged after
      5 days. The patient is currently without complaints at 5 months postoperatively.

PMID- 17022901
TI  - [Ileocecal valve lipoma. Case report and review of the literature].
AB  - BACKGROUND: Lipomas are the most frequent benign tumors of the digestive tract
      and 50% are localized in the colon. Most are found submucosally and may vary in
      their incidence, localization, symptoms and pathogenesis, making diagnosis
      difficult. We undertook this study to learn the different presentations of an
      ileocecal valve (ICV) lipoma and conduct a review of the literature due to this
      uncommon location. CASE PRESENTATION: We present the case of a 78-year-old female
      with intermittent small bowel occlusion, abdominal distention and constipation.
      Colonoscopy showed a submucous tumor at the ICV, CT scan showed a tumor at the
      ICV with fat density. Laparotomy was performed with primary resection of the
      lesion by cecotomy, frozen section was reported as nonmalignant so a primary
      closure without ICV involvement was achieved. Definitive pathology revealed a
      benign lipoma. CONCLUSION: It is important to know the different presentations of
      these benign tumors because if there is mucosal ulceration they can be mistaken
      for a malignant lesion and lead to greater resections. Resection is necessary if
      they are symptomatic or >2 cm.

PMID- 17022902
TI  - [Zenker diverticuli. Report of two cases].
AB  - We present two cases of Zenker's diverticuli (or hypopharyngeal diverticuli),
      diagnosed and operated on in the Servicio de Cirugia General del Hospital General
      Docente "Martin Chang Puga" de Nuevitas. We classify the diverticuli, as well as
      the different diagnostic and surgical procedures. Both of the cases are male, in
      their 30s, with basic symptoms of dysphagia with solid foods and also with
      respiratory symptoms. Patients were surgically intervened, with a satisfactory
      postoperative evolution during a 2-year follow-up.

PMID- 17022903
TI  - [Head and neck cancer. Risk factors and prevention].
AB  - The frequency of squamous cell carcinoma originating in head and neck mucosae has
      increased worldwide in the last decade, particularly in countries with emerging
      economies; oral cavity cancer is ranked in 6th place for all neoplasias. We
      conducted a literature review related to epidemiology and risk factors in head
      and neck cancer in order to analyze the most significant etiological factors and
      to emphasize prevention of carcinoma originating in head and neck mucosae. The
      prognosis in head and neck cancer patients depends on the clinical stage at time
      of diagnosis; therefore, identification of high-risk populations, precancerous
      lesions and early diagnosis decrease mortality. Nevertheless, the major effort
      must be on primary prevention.

PMID- 17022904
TI  - [PET/CT tomography. Usefulness in oncology].
AB  - In order to have optimum results in oncological patients, precise evaluation,
      diagnosis and staging of the patient is necessary. Positron emission tomography
      (PET) yields a high negative predictive value through exploration of the entire
      body. It diagnoses the benign or malignant state of a neoplasm that has been
      detected by other imaging methods and establishes an extensive diagnosis previous
      to therapeutic treatment of a known cancer. It identifies residual tumor and
      changes produced after surgery, chemotherapy or radiotherapy and locates
      suspicious residual tumor clinically or by elevation of the tumor markers. It
      allows for a new extension study or re-staging after diagnosis of recurrence and
      permits early evaluation of response to a therapeutic regime and permits the
      search for a primary tumor in patients with metastasis of unknown origin. PET
      leads to a molecular functional imaging of cancer in the entire body.

PMID- 17022905
TI  - Information sharing.

PMID- 17022906
TI  - Cervical cancer in Canada: a response to the release of the CCS/NCIC Cancer
      Statistics 2006.

PMID- 17022907
TI  - Prenatal multivitamin supplementation and rates of congenital anomalies: a meta
      analysis.
AB  - BACKGROUND: The use of folic acid-fortified multivitamin supplements has long
      been associated with decreasing the risk of neural tube defects. Several studies
      have also proposed the effectiveness of these supplements in preventing other
      birth defects; however, such effects have never been systematically examined.
      OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the
      protective effect of folic acid-fortified multivitamin supplements on other
      congenital anomalies. METHODS: We searched Medline, PubMed, EMBASE, Toxline,
      Healthstar, and Cochrane databases for studies describing the outcome of
      pregnancies in women using multivitamin supplements that were published in all
      languages from January 1966 to July 2005. The references from all collected
      articles were reviewed for additional articles. Two independent reviewers who
      were blinded to the source and identity of the articles extracted data based on
      predetermined inclusion and exclusion criteria. Using a random effects model,
      rates of congenital anomalies in babies born to women who were taking
      multivitamin supplements were compared with rates in the offspring of controls
      who were not. RESULTS: From the initial search, 92 studies were identified; 41 of
      these met the inclusion criteria. Use of multivitamin supplements provided
      consistent protection against neural tube defects (random effects odds ratio[OR]
      0.67, 95% confidence intervals [95% CI] 0.58-0.77 in case control studies; OR
      0.52, 95% CI 0.39-0.69 in cohort and randomized controlled studies),
      cardiovascular defects (OR 0.78, 95% CI 0.67-0.92 in case control studies; OR
      0.61, 95% CI 0.40-0.92 in cohort and randomized controlled studies), and limb
      defects (OR 0.48, 95% CI 0.30-0.76 in case control studies; OR 0.57, 95% CI 0.38
      0.85 in cohort and randomized controlled studies). For cleft palate, case control
      studies showed OR 0.76 (95% CI 0.62-0.93), and cohort and randomized controlled
      studies showed OR 0.42 (95% CI 0.06-2.84); for oral cleft with or without cleft
      palate, case control studies showed OR 0.63 (95% CI 0.54-0.73), and cohort and
      randomized controlled studies showed OR 0.58 (95% CI 0.28-1.19); for urinary
      tract anomalies, case control studies showed OR 0.48 (95% CI 0.30-0.76), and
      cohort and randomized controlled studies showed OR 0.68 (95% CI 0.35-1.31); and
      for congenital hydrocephalus case control studies showed OR 0.37 (95% CI 0.24
      0.56), and cohort and randomized controlled studies showed OR 1.54 (95% CI 0.53
      4.50). No effects were shown in preventing Down syndrome, pyloric stenosis,
      undescended testis, or hypospadias. CONCLUSION: Maternal consumption of folic
      acid-containing prenatal multivitamins is associated with decreased risk for
      several congenital anomalies, not only neural tube defects. These data have major
      public health implications, because until now fortification of only folic acid
      has been encouraged. This approach should be reconsidered.

PMID- 17022908
TI  - The importance of a postpartum 75 g oral glucose tolerance test in women with
      gestational diabetes.
AB  - OBJECTIVE: To compare the ability of the fasting plasma glucose (FPG) level with
      the ability of the 2-hour oral glucose tolerance test (OGTT) to identify women
      with any form of glucose intolerance within the first six postpartum months.
      METHODS: In a retrospective, observational analysis, the predictive ability of
      the FPG level was compared with that of the 2-hour OGTT in 275 women followed for
      gestational diabetes who returned for postpartum testing. RESULTS: With use of
      the FPG level alone, 4.4% of the women were found to have an FPG 7.0 mmol/L,
      identifying diabetes mellitus (DM); 2.5% had an FPG in the range 6.1-6.9 mmol/L,
      identifying impaired fasting glucose (IFG); and 93% had an FPG 6.0 mmol/L, i.e.,
      within the normal range. Using the 2-hour 75g OGTT, 5% of women were found to
      have either an FPG 7.0 mmol/L or a 2-hour plasma glucose (PG) 11.1 mmol/L,
      identifying DM; 2.5% had an FPG of 6.1-6.9 mmol/L, identifying IFG; and 32% had a
      2-hour PG of 7.8-11.0 mmol/L, identifying impaired glucose tolerance (IGT). Of
      the women with any glucose abnormality postpartum, an FPG level alone detected
      15.8%, the post-glucose load level detected 97.5%, and an OGTT detected 100% of
      the women. An FPG level alone in 39% of cases failed to detect either IGT or DM
      and in 54% of cases, type 2 DM. CONCLUSION: In view of the potential for early,
      effective prevention of DM, the optimal method for detecting glucose
      abnormalities in women within six months post partum is a 2-hour OGTT.

PMID- 17022909
TI  - Prevalence and correlates of cervical cancer screening among injection drug
      users.
AB  - OBJECTIVE: Access to cervical cancer screening may be lower among lower income
      and socially disadvantaged populations. However, few studies have specifically
      examined factors associated with cervical cancer screening among socially
      marginalized populations, especially in settings with free health care systems.
      METHODS: The present study was conducted to examine the prevalence and correlates
      of cervical cancer screening among injection drug users. We examined rates of
      Papanicolaou (Pap) smear testing among female participants in the Vancouver
      Injection Drug Users Study (VIDUS). Univariate and logistic regression analyses
      were used to evaluate factors associated with cervical cancer screening. RESULTS:
      During the period from December 2004 to May 2005, 297 female injection drug users
      were seen. In logistic regression analyses, age (adjusted odds ratio [AOR]=0.70;
      95% confidence intervals [CI] 0.53, 0.92, P=0.010), HIV infection (AOR=2.46; 95%
      CI 1.41,4.26, P=0.001), hepatitis C infection (AOR=0.25; 95% CI 0.09,0.71,
      P=0.010), and having visited a family physician in the prior six months (OR=3.10;
      95% CI 1.58, 6.07, P=0.001) were independently associated with recent cervical
      cancer screening. CONCLUSIONS: After adjustment for regular physician visits, HIV
      infection was associated with elevated rates of cervical screening. This is
      reassuring, given the elevated risk of cervical cancer among this population.
      Interventions may be required to improve uptake of screening among older
      injection drug users and drug users infected with hepatitis C.

PMID- 17022910
TI  - A survey of Canadian websites providing information about female urinary
      incontinence.
AB  - OBJECTIVE: Urinary incontinence (UI) is a prevalent health issue that has
      significant detrimental effects on quality of life. The Internet offers a unique
      vehicle for incontinent women to access information that could facilitate
      conservative self-help therapy. An evaluation of Canadian websites offering
      female UI information was conducted to determine their quality and readability.
      METHODS: We evaluated websites using published general quality criteria for
      health sites and a quality assessment tool compiled by the authors for specific
      UI information derived from published, peer-reviewed clinical practice
      guidelines. Three health care professionals reviewed sites for quality, Canadian
      content, and interactivity. The readability of health information was also
      evaluated. RESULTS: Fifty-six Canadian sites (18 professional, 22 organizational,
      16 commercial) were evaluated. Significant agreement was found among the raters'
      evaluations on all measures. For all sites, the mean scores were general quality,
      9/14; specific UI quality, 30/122; reading ease, 37/100; grade level, 10.9. The
      median score for Canadian content was high, but for interactivity it was low. The
      only significant difference between site types was for general quality (F
      [2,165]=3.38, P=0.036). Post hoc Tukey's tests showed a significant difference
      between organizational and commercial sites, with organizational sites having
      higher general quality. CONCLUSION: Canadian websites providing female UI
      information have moderately high general quality, low specific UI information
      quality, minimal interactivity, and more than minimal Canadian content. The
      reading level of most sites is too high for average consumers. A webliography of
      the best sites has been developed to guide patients.

PMID- 17022911
TI  - Postpartum uterine wound dehiscence: a case report.
AB  - INTRODUCTION: Late postpartum hemorrhage following a Caesarean section (CS) is
      uncommon. A partial or complete dehiscence of the lower segment CS incision is a
      rare but possible cause. CASE: A 33-year-old woman underwent a lower segment CS
      for chorioamnionitis and failure to progress in labour at 40 weeks and 5 days of
      gestation. On the 43rd postpartum day, she developed heavy vaginal bleeding.
      Emergency laparotomy revealed a complete dehiscence of the lower uterine segment
      incision. A subtotal hysterectomy was performed to control the bleeding, and the
      postoperative course was uneventful. CONCLUSION: Dehiscence of a lower uterine
      segment incision is a rare but potentially dangerous cause of late postpartum
      hemorrhage.

PMID- 17022912
TI  - Fat-soluble vitamin deficiency in pregnancy: a case report and review of
      abetalipoproteinemia.
AB  - BACKGROUND: Abetalipoproteinemia (ABL) is a metabolic disorder resulting in poor
      absorption of fat-soluble vitamins. CASE: Two pregnancies in a woman with ABL are
      reported, contrasting outcomes with subtherapeutic and normal vitamin levels.
      CONCLUSION: Fat-soluble vitamin levels in pregnancy are critical for many aspects
      of fetal development. This report details a congenital ophthalmologic finding
      that may be associated with vitamin A deficiency.

PMID- 17022913
TI  - Pregnancy with uterine vascular malformations associated with hemorrhagic
      hereditary telangiectasia: a case report.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal
      dominant condition. It is rarely seen in pregnancy and even more rarely has
      uterine manifestations. CASE: A 29-year-old primigravid woman with HHT was noted
      to have vascular manifestations of her disease in the lower uterus, distal
      rectum, pelvis, and bladder before pregnancy. Prior to delivery, a case
      conference was held, involving representatives of the departments of vascular
      surgery, hematology, radiology, anaesthesiology, maternal-fetal medicine,
      neonatology, and laboratory medicine, and other appropriate health professionals.
      A successful elective Caesarean section was performed at term, with a good
      outcome for both mother and child. CONCLUSION: regnancies in women with HHT and
      associated uterine vascular manifestations have been rarely reported, and
      published information is minimal. We present a case of a successful operative
      delivery following careful multidisciplinary antepartum care.

PMID- 17022914
TI  - Breast self-examination.
AB  - OBJECTIVE: To examine the value of teaching regular breast self-examination
      (BSE). OUTCOME: Reduction of benign biopsy rates. BENEFITS: To provide better
      advice for women about the risks and benefits of BSE, and to ensure that women
      who choose to practise BSE are taught to perform it proficiently. SUMMARY
      STATEMENT: Routine teaching of BSE does not reduce mortality and likely increases
      benign biopsy rates. (I) RECOMMENDATIONS: 1. Breast self-examination should not
      be routinely taught to women. (ID) 2. A full discussion of breast self
      examination, including risks, should be provided for the woman who requests it.
      (IIIA) 3. If a woman makes an informed decision to practise BSE, care providers
      should ensure she is taught the skills and that she performs self-examination
      proficiently. (IIIA) VALIDATION: This committee opinion was developed by the
      Breast Disease Committee of the Society of Obstetricians and Gynaecologists of
      Canada. It was approved by the Executive and Council of the Society of
      Obstetricians and Gynaecologists of Canada. SPONSOR: The Society of Obstetricians
      and Gynaecologists of Canada.

PMID- 17022915
TI  - Ruminative worrying during pregnancy: a case series.
AB  - BACKGROUND: Most women worry to some extent during pregnancy about exposure to
      agents that might harm their babies. CASES: We describe three women who worried
      excessively throughout pregnancy about harming their babies because of exposure
      to agents including, but not limited to, psychotropic drugs. These women were
      extremely resistant to reassurances that their babies would not be adversely
      affected, and it is likely there are more women in the community who fit this
      profile. We have described a number of management strategies that we found
      effective in caring for these women during pregnancy. CONCLUSION: A collaborative
      effort between caregivers in psychiatry and obstetrics, as well as other health
      professionals, is required to provide management for these women during
      pregnancy.

PMID- 17022916
TI  - Planning for the future.

PMID- 17022917
TI  - The Ottawa Hospital's Clinical Practice Guideline for the Second Stage of Labour.
AB  - The management of the second stage of labour remains controversial, and there are
      very few comprehensive evidence-based clinical practice guidelines to assist care
      providers. We describe an approach to developing a local clinical practice
      guideline that included extensive review of the literature; use of a guideline
      appraisal instrument to assess methodological rigour, content, clarity and
      applicability; use of a recommendation matrix; drafting a local guideline;
      obtaining formal feedback; making revisions; and designing an implementation and
      evaluation plan. Recommendations from this guideline include timelines for the
      total length of second stage, waiting time, and pushing time. Positioning of the
      woman, use of oxytocin, and fetal assessment are also discussed. This guideline
      is not intended to be used for women with multiple gestation and women attempting
      vaginal birth after Caesarean (VBAC) or in clinical situations where little
      evidence on best practice exists and management is individualized. We advocate an
      approach to the second stage of labour that enhances patient safety through team
      planning, communication, and documentation.

PMID- 17022918
TI  - Pre-conception practices among family physicians and obstetrician-gynaecologists:
      results from a national survey.
AB  - OBJECTIVE: To determine the pre-conception practices among obstetrician
      gynaecologists and family physicians in Canada. METHODS: Between October 2001 and
      May 2002, a survey was mailed to a national random sample of obstetricians and
      gynaecologists (n = 539) and family physicians (n = 2378) who were current
      members of the College of Family Physicians of Canada or the Society of
      Obstetricians and Gynaecologists of Canada. RESULTS: Response rates were 41.7%
      among obstetrician-gynaecologists and 31.1% among family physicians. More than
      85% of physicians frequently discussed birth control and Pap testing with women
      of childbearing age, but fewer than 60% frequently obtained a detailed history of
      alcohol use. Fewer than 50% of physicians frequently discussed the following with
      women of childbearing age: weight management, workplace stress, mental health,
      addiction history, or the risks of substance use during pregnancy. Fewer than 15%
      enquired about a history of sexual or emotional abuse. Family physicians were
      significantly more likely than obstetrician-gynaecologists to discuss mental
      health (41.1% vs. 28.1%), depression (44.5% vs. 29.0%), and history of alcohol
      use (59.8% vs. 47.9%) with women of childbearing age (all P < 0.05). Obstetrician
      gynaecologists were significantly more likely than family physicians to discuss
      folic acid (57.8% vs. 47.2%), sexual abuse (18.2% vs. 10.8%), smoking (56.0% vs.
      46.1%), and drug use (45.8% vs. 35.9%) (all P < 0.05) with women of childbearing
      age who were not pregnant. CONCLUSION: There are missed opportunities in pre
      conception screening to identify women with suboptimal reproductive health status
      who are at risk for adverse conception, pregnancy, and birth outcomes. Physician
      training in identification of women at risk would allow for increased primary and
      secondary prevention efforts through referral to appropriate treatment and
      resources.

PMID- 17022919
TI  - Short-term morbidity and long-term recurrence rate of ovarian dermoid cysts
      treated by laparoscopy versus laparotomy.
AB  - OBJECTIVE: To compare the short-term morbidity and the long-term recurrence rate
      of ovarian dermoid cysts in women treated conservatively by laparoscopy with the
      outcomes in women treated by laparotomy. METHODS: This retrospective multicentre
      cohort study compared the outcomes of removal of dermoid cysts by laparoscopy
      with removal by laparotomy. All specimens were confirmed histologically as
      dermoid cysts. We reviewed all medical records and identified all surgical
      interventions for dermoid cysts over a 10-year period (1993-2003) in two academic
      centres in Quebec City. Of the 299 women treated for ovarian dermoid cysts, 167
      were treated by laparotomy and 132 were treated by laparoscopy. To compare short
      term morbidity, we excluded those who had undergone ophorectomy or any
      concomitant surgery, and we consequently reviewed the records of 98 patients in
      the laparotomy group and 100 patients in the laparoscopy group. To compare long
      term recurrence rates we excluded only those patients who had had oophorectomy.
      In total, 245 women with available follow-up were identified as having ovarian
      cystectomy (95 in the laparoscopy group and 150 in the laparotomy group). Two
      tailed Fisher exact test was used for analysis of categorical variables, and
      Student t test or Wilcoxon rank test were used for analysis of continuous
      variables comparing the two groups. Life table analysis using the Kaplan-Meier
      method was performed to assess the risk of long-term recurrence. RESULTS: The
      mean diameter of the cyst in women who had a laparotomy was significantly larger
      than in women who had laparoscopy (8.27 cm vs. 5.94 cm), and significantly more
      women in the laparotomy group had bilateral cysts (16% vs. 5% in the laparoscopy
      group). In women who had laparoscopy, operating time was greater (P = 0.0363),
      but blood loss was less (P < 0.0001) and duration of hospital stay (P < 0.0001)
      was shorter. Spillage of the cyst's contents occurred in 18% of cases in the
      laparoscopy group and in 1% in the laparotomy group. Conversions of laparoscopy
      to laparotomy occurred in 11% of cases, mainly because of cyst size.
      Postoperative complication rates were similar in the two groups. Reintervention
      rate was 4.2% in the laparoscopy group and 0% in the laparotomy group (P =
      0.0217). Using life table analysis, the probability of recurrence at two years
      was 7.6% (95% confidence intervals 2.9, 19.2) in the laparoscopy group and 0% in
      the laparotomy group. CONCLUSION: Ovarian cystectomy performed by laparoscopy is
      associated with a higher incidence of intra-abdominal spillage than laparotomy,
      but this not associated with any increase in morbidity. Laparoscopic treatment
      results in a shorter hospital stay and less intraoperative blood loss than
      laparotomy, but it is associated with a significantly higher risk of recurrence.

PMID- 17022920
TI  - Assessment of costs associated with outpatient total laparoscopic hysterectom.
AB  - OBJECTIVE: To assess the costs associated with the performance of outpatient
      total laparoscopic hysterectomy. METHODS: This was a retrospective cohort study
      involving 224 consecutive patients undergoing total laparoscopic hysterectomy
      (TLH) by a single surgeon in the Regina General Hospital. Outcomes included costs
      associated with the initial procedure as well as those associated with any
      intraoperative or postoperative complications. RESULTS: The mean age of the
      patients was 42.7 years. The mean uterine weight was 205 grams (range 69-1163 g),
      the mean operating time was 79 minutes, and the mean blood loss was 89 cc. The
      mean postoperative stay in the day surgery unit (DSU) was 354 minutes. Ten
      patients required admission from the DSU, and nine patients were admitted more
      than 24 hours after surgery. The total number of admission days was 24, which
      cost 21,900 US dollars. The total cost of all disposables was 127,373 US dollars
      and the cost associated with the stays in day surgery was 89,600 US dollars. The
      total cost for the 224 TLH procedures was 238,573 US dollars, and the average
      cost per TLH was 1065 US dollars. CONCLUSION: Outpatient TLH can be completed
      safely and with costs that are lower than those incurred by patients having short
      stay vaginal hysterectomy in our institution. Outpatient TLH offers the
      opportunity to save health care costs and a procedure with excellent results.

PMID- 17022921
TI  - Guidelines for the number of embryos to transfer following in vitro
      fertilization.
AB  - OBJECTIVE: To review the effect of the number of embryos transferred on the
      outcome of in vitro fertilization (IVF), to provide guidelines on the number of
      embryos to transfer in IVF-embryo transfer (ET) in order to optimize healthy live
      births and minimize multiple pregnancies. OPTIONS: Rates of live birth, clinical
      pregnancy, and multiple pregnancy or birth by number of embryos transferred are
      compared. OUTCOMES: Clinical pregnancy, multiple pregnancy, and live birth rates.
      EVIDENCE: The Cochrane Library and MEDLINE were searched for English language
      articles from 1990 to April 2006. Search terms included embryo transfer (ET),
      assisted reproduction, in vitro fertilization (IVF), ntracytoplasmic sperm
      injection (ICSI), multiple pregnancy, and multiple gestation. Additional
      references were identified through hand searches of bibliographies of identified
      articles. VALUES: Available evidence was reviewed by the Reproductive
      Endocrinology and Infertility Committee and the Maternal-Fetal Medicine Committee
      of the Society of Obstetricians and Gynaecologists of Canada and the Board of the
      Canadian Fertility and Andrology Society, and was qualified using the Evaluation
      of Evidence Guidelines developed by the Canadian Task Force on the Periodic
      Health Exam. BENEFITS, HARMS, AND COSTS: This guideline is intended to minimize
      the occurrence of multifetal gestation, particularly high-order multiples (HOM),
      while maintaining acceptable overall pregnancy and live birth rates following IVF
      ET.

PMID- 17022922
TI  - Can complementary and alternative medicine clinical cancer research be
      successfully accomplished? The Mayo Clinic-North Central Cancer Treatment Group
      experience.
AB  - Some critics question whether research on complementary and alternative
      modalities for patients with cancer can be done efficiently in traditional
      clinical settings. This article reviews a program of complementary medicine
      research that has been done in a traditional clinical setting over the past 30
      years. Trials using complementary therapies for both symptom management and
      cancer treatment done by the Mayo Clinic and the North Central Cancer Treatment
      Group are reviewed. Twenty-seven studies have been developed using complementary
      therapies, addressing such issues as mucosal and epidermal toxicity, hot flashes,
      lymphedema, anorexia and cachexia, insomnia, cognitive dysfunction, fatigue, and
      cancer treatment. Nineteen of them have been completed and have had results
      published in peer-reviewed clinical journals, whereas two manuscripts are in
      press. Two other trials have recently completed accrual, and the data are being
      analyzed so that manuscripts can be prepared. In addition, four clinical trials
      are actively accruing patients. The data presented in this article demonstrate
      that complementary and alternative medicine research can be done in a
      scientifically sound manner. Well-designed and adequately powered studies can be
      implemented, and large numbers of patients can be accrued. The resulting research
      evaluations can be published in peer-reviewed medical journals.

PMID- 17022923
TI  - Intravenous nutrient therapy eliminated androgen deprivation therapy-induced hot
      flashes in two men with prostate cancer.
AB  - Androgen deprivation therapy (ADT) is commonly used for the treatment of prostate
      cancer. For many undergoing ADT, hot flashes can affect and significantly reduce
      quality of life. Traditional medications for hot flashes are limited by both
      clinical effectiveness and side effects. In two case reports, ADT-induced hot
      flashes quickly resolved after a short course of a specific intravenous
      combination of vitamins and minerals. This therapeutic approach may have
      potential for the treatment of ADT-induced hot flashes.

PMID- 17022924
TI  - Breast cancer patients' perspectives on and use of complementary and alternative
      medicine: a study by the Susan G. Komen Breast Cancer Foundation.
AB  - The purpose of this study was to examine patterns and predictors of complementary
      and alternative medicine (CAM) among breast cancer patients. A review of the
      existing survey literature on CAM use for breast cancer was conducted with a
      series of eight focus groups (N = 67) to further examine the perspectives of
      breast cancer patients on CAM. The rates of CAM use varied from 17 to 75%, with a
      mean of 45%. Vitamins and minerals and herbs were the most frequently cited
      categories. Users tended to be younger, more educated, and more likely to have
      used CAM prior to their diagnosis. Focus group data indicate that breast cancer
      patients use a wide array of CAM for a variety of reasons, including symptom
      management, improving quality of life, and enhancing immune function. Although
      women rely on a variety of resources for information, they frequently experience
      frustration owing to the absence or conflicting nature of such information.
      Communication with conventional providers about CAM is frequently experienced as
      either unsupportive or not helpful by many patients. The results point to the
      value of developing better evidence-based informational resources related to CAM
      and cancer and the need for physicians to become better educated about CAM and
      how to communicate more effectively with their breast cancer patients about it.

PMID- 17022925
TI  - Evidence-based systematic review of saw palmetto by the Natural Standard Research
      Collaboration.
AB  - Here presented is an evidence-based systematic review including written and
      statistical analysis of scientific literature, expert opinion, folkloric
      precedent, history, pharmacology, kinetics/dynamics, interactions, adverse
      effects, toxicology, and dosing.

PMID- 17022926
TI  - Lifestyle, biomechanical, and bioenergetic complementary therapies in pediatric
      oncology.
AB  - After the diagnosis of cancer in a child is made, many families complement
      conventional medical care with lifestyle changes including diet, exercise,
      environment, and mind-body therapies. Biomechanical, bioenergetic, and other
      therapies are also sometimes sought. These include massage, chiropractic,
      acupuncture/acupressure, therapeutic touch, Reiki, homeopathy, and prayer. Some
      of these complementary therapies have well-established roles in cancer therapy
      for children, whereas others are controversial and require more research.

PMID- 17022927
TI  - How to randomize.
AB  - Randomized trials are an important method for deciding whether integrative
      oncology therapies do more good than harm. Many investigators do not pay
      sufficient attention to randomization procedures, and several studies have shown
      that only a fraction of trial reports describe randomization adequately. The
      purpose of randomization is to prevent selection bias: randomization procedures
      must therefore ensure that researchers are unable to predict the group to which a
      patient will be randomized until the patient is unambiguously registered on
      study; moreover, researchers must be unable to change a patient's allocation
      after the patients are registered. The use of telephone randomization and opaque
      envelopes has been suggested as a good randomization method, but both can be
      subverted. Randomization should be conducted either by a pharmaceutical company,
      which sends blinded medication to the hospital pharmacy, or by a secure, password
      protected database system. Computer randomization can easily incorporate
      extensions of randomization, such as blocking, stratification, and minimization,
      which can help ensure balance between groups.

PMID- 17022928
TI  - Noni (Morinda citrifolia).

PMID- 17022929
TI  - The prevalence and reliability of visibility aid and other risk factor data for
      uninjured cyclists and pedestrians in Edmonton, Alberta, Canada.
AB  - This study was conducted to determine the prevalence and reliability of risk
      factors collected on uninjured cyclists-pedestrians in Edmonton, Alberta, and
      what characteristics predict cyclist-pedestrian visibility. At randomly selected
      locations from July 2004 to August 2004, two independent observers recorded
      cyclist-pedestrian characteristics such as age, sex, clothing color, use of
      reflectors, flags, helmets, and a subjective impression of visibility. Data were
      collected on 836 individuals; most were either walking/jogging (approximately
      63%) or cycling (approximately 33%). For non-cyclists, the prevalence of bright
      colored clothing on the trunk ranged from 12.7 to 14.7%. Few people used any kind
      of reflective strips. Inter-observer agreement (Kappa) ranged from 0.37
      (visibility assessment) to 0.99 (sex). For cyclists, 17-19% of headgear was
      brightly colored, and 13-14% was white. Approximately one-fourth had a front
      light; half had a rear reflector. Few cyclists used a flag and just over half
      used spoke reflectors. Kappa ranged from 0.35 (observer assessed speed) to 0.95
      (head gear and sex). A major trunk color of orange, red, yellow or white resulted
      in a higher visibility rating for both cyclists and pedestrians. The results
      indicate a low prevalence of visibility aid use among cyclists and pedestrians,
      but there appears to be acceptable inter-observer reliability for most data
      collected. Further work is required before an overall visibility rating can be
      used in place of component scores.

PMID- 17022930
TI  - Top-down influences make saccades deviate away: the case of endogenous cues.
AB  - We tested a recent hypothesis suggesting that the eye deviates away from a
      location when top-down preparation can influence target selection. Participants
      had to make an eye movement to a peripheral target. Before the upcoming target, a
      central cue indicated the likely target location. Results show that when the
      target was presented at a location different from that indicated by the cue, eye
      movements to the target deviated away from the cued location. Because central
      cues are under top-down control, the present results are in line with a
      determining role of top-down preparation on saccade direction. These results
      contrast with the findings reported in a similar paradigm executed with hand
      movements, in which the movements were mostly initiated in the direction of the
      cued location. Therefore, we conclude that inhibitory effects typically observed
      when executing eye movements may not be observed when executing hand movements in
      similar conditions.

PMID- 17022931
TI  - Pallor as a sign of anaemia in small Tanzanian children at different health care
      levels.
AB  - BACKGROUND: Anaemia is a major complication of Plasmodium falciparum malaria
      among small children in sub-Saharan Africa. We studied the performance of the
      Integrated Management of Childhood Illness (IMCI) recommended assessment of
      no/some/severe pallor as predictor of anaemia in health surveys at community
      level and in clinical practice in an out patient department (OPD) and in a
      hospital ward in rural Tanzania. METHODS: The study was undertaken among 6-36
      months old children. Pallor was evaluated as a combined assessment of
      conjunctiva, tongue and palms and categorised as no, some or severe pallor.
      Packed cell volume (PCV) was measured and related to pallor. FINDINGS: A total of
      740 examinations were performed at village, OPD and in the hospital ward. The
      prevalences of severe pallor were 0%, 1.5% and 7% respectively. The prevalences
      of any pallor were 14%, 41% and 86%. The prevalences of severe anaemia (PCV<21%)
      were 1%, 5% and 81% and of any anaemia (PCV<33%) 68%, 73% and 98%. Severe pallor
      could not detect severe anaemia. The sensitivities were only 0%, 0% and 8%. The
      sensitivities of any pallor to detect severe anaemia were however 86% and 98% for
      children at the health care facility level, but still of relatively poor
      predictive values since the specificities were only 61% and 68%. INTERPRETATION:
      Division of pallor into some or severe degrees was of no use at any health care
      level. The identification of any pallor was of no use at village level, but it
      may possibly be of some value as a screening test for severe anaemia at health
      care facilities, if additional assessment is included in view of the low
      specificity and positive predictive value of the finding.

PMID- 17022932
TI  - Algorithm for the diagnosis of anaemia without laboratory facilities among small
      children in a malaria endemic area of rural Tanzania.
AB  - BACKGROUND: Anaemia among small children in tropical Africa is common and often
      caused by infection with Plasmodium falciparum. The diagnosis of anaemia is
      difficult without a laboratory estimation of haemoglobin. The aim of this study
      was to examine if clinical findings related to malaria and anaemia would help to
      detect moderate and/or severe anaemia in children in rural Tanzania. METHODS:
      Children between 6 and 36 months were examined by health workers in an Out
      Patient Department (OPD) to detect severe anaemia (packed cell volume, PCV< or
      =20%) and in a cross sectional survey at village level to identify moderate
      anaemia (PCV 21-25%). History of recent fever and treatments was recorded and a
      clinical examination was performed. FINDINGS: In the survey, comparison of 65
      moderately anaemic children with 373 mild/non anaemic children revealed no
      differences in history of fever or in the clinical examination. In the OPD
      comparison of 100 severely anaemic children with 116 non-severely anaemic control
      children revealed that pallor, respiratory rate, number of fever days last week,
      deteriorated general condition, heart rate, age, splenomegaly, low body weight
      and elevated body temperature were all indicators of severe 'anaemia, only
      pallor, respiratory rate, fever days and palpable spleen however, remained
      associated with severe anaemia in multiple regression analysis. The combination
      of any pallor and either respiratory rate >55/min or fever >3 days, could predict
      severe anaemia with a sensitivity of 96% and a specificity of 71%. This was
      better than the currently recommended signs of severe pallor or an approximation
      of the Integrated Management of Childhood Illness (IMCI) criteria's for referral
      of children. INTERPRETATION: At primary health care level detection of severe
      anaemia can be improved by information about fever duration and determination of
      respiratory rate in children with pallor.

PMID- 17022933
TI  - Polarization model for poorly-organized interfacial water: hydration forces
      between silica surfaces.
AB  - The main goal of this paper is to review the theoretical models which can be used
      to describe the interactions between silica surfaces and to show that a model
      proposed earlier by the authors (the polarization model), which accounts
      concomitantly for double layer and hydration forces, can be adapted to explain
      recent experiments in this direction. When the water molecules near the interface
      were considered to have an ice-like structure, a strong coupling between the
      double layer and hydration forces (described by the correlation length between
      neighboring dipoles, lambda(m)) generates long range interactions, larger than
      the experimentally determined interactions between silica surfaces. Arguments are
      brought that a gel layer is likely to be formed on the surface of silica, which,
      by generating disorder in the interfacial water layers, can decrease strongly the
      value of lambda(m). Since the prediction of lambda(m) involves a choice for the
      microscopic structure of water, which is often unknown, the polarization model is
      also presented here as a phenomenological theory, in which lambda(m) is used as a
      fitting parameter. Two extreme cases are considered. In one of them, the water
      molecules near the interface are considered to have an ice-like structure,
      whereas in the other they are considered randomly distributed. In the first case,
      the dipole correlation length lambda(m)=14.9 Angstrom. In the second limiting
      case, lambda(m) can be of the order of 1 Angstrom. It is shown that, for
      lambda(m)=4 Angstrom, a more than qualitative agreement with the experiment could
      be obtained, for reasonable values of the parameters involved (e.g. surface
      dipole strength and density, dipole location, surface charge).

PMID- 17022934
TI  - Cold acclimation and oxygen consumption in the thymus.
AB  - Mitochondrial uncoupling protein 1 is usually associated with brown adipose
      tissue but has recently been discovered in rat and mouse thymus. We wished to
      establish whether there was a thermogenic role for UCP 1 in thymus and thus
      examined the effect of 5 weeks cold-acclimation on rat thymus tissue abundance,
      thymocyte oxygen consumption, thymus mitochondrial abundance, uncoupling protein
      1 expression and function. We found that thymocytes from cold-acclimated rats had
      oxygen consumption rates 8 times less than those from rats held at room
      temperature and that thymocytes from cold-acclimated rats or rats kept at room
      temperature were noradrenaline insensitive. In addition, we found that thymus
      tissue or mitochondrial abundance was not increased after cold-acclimation.
      However uncoupling protein 1 expression per unit mass of mitochondria was
      increased after cold-acclimation, as determined by immunoblotting (approximately
      1.7-fold) and GDP binding (approximately 1.5-fold). Consistent with our protein
      expression data, we also observed an increased, state 4 (approximately 1.5-fold),
      GDP-inhibitable (approximately 1.3-fold) and palmitate activatable (approximately
      1.6-fold) oxygen consumption rates in isolated thymus mitochondria. However,
      extrapolation of our data showed that cold-acclimation only increased the amount
      of UCP 1 per gram of thymus tissue approximately 1.2-fold. Taken together, we
      conclude that UCP 1 does not have a thermogenic role in thymus.

PMID- 17022936
TI  - Structural analyses of O-glycan sugar chains on IgA1 hinge region using SELDI
      TOFMS with various lectins.
AB  - The aim of the study was to develop a simple and precise method for identifying
      glycosylation of the IgA hinge region using surface-enhanced laser
      desorption/ionization (SELDI)-TOFMS with a lectin-coupled ProteinChip array.
      Serum IgA was isolated using an anti-IgA antibody column. Following reduction,
      alkylation, and trypsin digestion, the IgA fragments were applied on the
      ProteinChip coupled with jacalin, peanut agglutinin (PNA), or Vilsa villosa
      lectin (VVL). The SELDI-TOFMS peaks corresponding to the fragments containing
      IgA1 hinge glycopeptides trapped by each lectin were compared. The jacalin-, PNA
      , and VVL-immobilized ProteinChips detected 13, 4, and 2 peaks, respectively. One
      major peak was confirmed as a glycopeptide by MS/MS analysis. These results
      suggest that a lectin-immobilized ProteinChip assay can be used to simplify the
      procedures for the analyses of the O-glycans in IgA1 hinge. This method
      potentially makes it possible to identify a disease-specific glycoform by
      selecting the appropriate ligand-coupled ProteinChip array.

PMID- 17022935
TI  - Relationship between glycogen accumulation and the laforin dual specificity
      phosphatase.
AB  - Laforin, encoded by the EPM2A gene, is a dual specificity protein phosphatase
      that has a functional glycogen-binding domain. Mutations in the EPM2A gene
      account for around half of the cases of Lafora disease, an autosomal recessive
      neurodegenerative disorder, characterized by progressive myoclonus epilepsy. The
      hallmark of the disease is the presence of Lafora bodies, which contain
      polyglucosan, a poorly branched form of glycogen, in neurons and other tissues.
      We examined the level of laforin protein in several mouse models in which muscle
      glycogen accumulation has been altered genetically. Mice with elevated muscle
      glycogen have increased laforin as judged by Western analysis. Mice completely
      lacking muscle glycogen or with 10% normal muscle glycogen had reduced laforin.
      Mice defective in the GAA gene encoding lysosomal alpha-glucosidase (acid
      maltase) overaccumulate glycogen in the lysosome but did not have elevated
      laforin. We propose, therefore, that laforin senses cytosolic glycogen
      accumulation which in turn determines the level of laforin protein.

PMID- 17022937
TI  - Analyzing the cellular contribution of bone marrow to fracture healing using bone
      marrow transplantation in mice.
AB  - The bone marrow is believed to play important roles during fracture healing such
      as providing progenitor cells for inflammation, matrix remodeling, and cartilage
      and bone formation. Given the complex nature of bone repair, it remains difficult
      to distinguish the contributions of various cell types. Here we describe a mouse
      model based on bone marrow transplantation and genetic labeling to track cells
      originating from bone marrow during fracture healing. Following lethal
      irradiation and engraftment of bone marrow expressing the LacZ transgene
      constitutively, wild type mice underwent tibial fracture. Donor bone marrow
      derived cells, which originated from the hematopoietic compartment, did not
      participate in the chondrogenic and osteogenic lineages during fracture healing.
      Instead, the donor bone marrow contributed to inflammatory and bone resorbing
      cells. This model can be exploited in the future to investigate the role of
      inflammation and matrix remodeling during bone repair, independent from
      osteogenesis and chondrogenesis.

PMID- 17022938
TI  - Myosin II activity is not essential for recruitment of myosin II to the furrow in
      dividing HeLa cells.
AB  - To elucidate whether phosphorylation of myosin II regulatory light chain (MRLC)
      is essential for myosin II recruitment to the furrow during cytokinesis, HeLa
      cells transfected with three types of GFP-tagged recombinant MRLCs, wild-type
      MRLC, non-phosphorylated form of MRLC, and phosphorylated form of MRLC, were
      examined. Living cell-imaging showed that both phosphorylated and non
      phosphorylated form of MRLCs were recruited to the equator at the same time after
      anaphase onset, suggesting that phosphorylation of MRLC is not responsible for
      recruitment of myosin II to the equator. Moreover, the treatment with an
      inhibitor of myosin II activity, blebbistatin, induced no effect on recruitment
      of those three recombinant MRLCs. During cytokinesis, phosphorylated but not non
      phosphorylated form of MRLC was retained in the equator. These results suggest
      that phosphorylation of MRLC is essential for retainment of myosin II in the
      furrow but not for initial recruitment of myosin II to the furrow in dividing
      HeLa cells.

PMID- 17022939
TI  - Characterization of genes encoding ABA 8'-hydroxylase in ethylene-induced stem
      growth of deepwater rice (Oryza sativa L.).
AB  - Ethylene and submergence enhance stem elongation of deepwater rice, at least in
      part, by reducing in the internode the endogenous abscisic acid (ABA) content and
      increasing the level of gibberellin A1 (GA1). We cloned and characterized the
      CYP707A5 and CYP707A6 genes, which encode putative ABA 8'-hydroxylase, the enzyme
      that catalyzes the oxidation of ABA. Expression of CYP707A5 was upregulated
      significantly by ethylene treatment, whereas that of CYP707A6 was not altered.
      Recombinant proteins from both genes expressed in yeast cells showed activity of
      ABA 8'-hydroxylase. This finding indicates that CYP707A5 may play a role in ABA
      catabolism during submergence- or ethylene-induced stem elongation in deepwater
      rice. Taken together, these results provide links between the molecular
      mechanisms and physiological phenomena of submergence- and ethylene-induced stem
      elongation in deepwater rice.

PMID- 17022940
TI  - Identification of pH-sensitive regions in the mouse prion by the cysteine
      scanning spin-labeling ESR technique.
AB  - We analyzed the pH-induced mobility changes in moPrP(C) alpha-helix and beta
      sheets by cysteine-scanning site-directed spin labeling (SDSL) with ESR. Nine
      amino acid residues of alpha-helix1 (H1, codon 143-151), four amino acid residues
      of beta-sheet1 (S1, codon 127-130), and four amino acid residues of beta-sheet2
      (S2, codon 160-163) were substituted for by cysteine residues. These recombinant
      mouse PrP(C) (moPrP(C)) mutants were reacted with a methane thiosulfonate
      sulfhydryl-specific spin labeling reagent (MTSSL). The 1/deltaH of the central
      (14N hyperfine) component (M(I) = 0) in the ESR spectrum of spin-labeled moPrP(C)
      was measured as a mobility parameter of nitroxide residues (R1). The mobilities
      of E145R1 and Y149R1 at pH 7.4, which was identified as a tertiary contact site
      by a previous NMR study of moPrP, were lower than those of D143R1, R147R1, and
      R150R1 reported on the helix surface. Thus, the mobility in the H1 region in the
      neutral solution was observed with the periodicity associated with a helical
      structure. On the other hand, the values in the S2 region, known to be located in
      the buried side, were lower than those in the S1 region located in the surface
      side. These results indicated that the mobility parameter of the nitroxide label
      was well correlated with the 3D structure of moPrP. Furthermore, the present
      study clearly demonstrated three pH-sensitive sites in moPrP, i.e., (1) the N
      terminal tertiary contact site of H1, (2) the C-terminal end of H1, and (3) the
      S2 region. In particular, among these pH-sensitive sites, the N-terminal tertiary
      contact region of H1 was found to be the most pH-sensitive one and was easily
      converted to a flexible structure by a slight decrease of pH in the solution.
      These data provided molecular evidence to explain the cellular mechanism for
      conversion from PrP(C) to PrP(Sc) in acidic organelles such as the endosome.

PMID- 17022942
TI  - Ephrin A5 expression promotes invasion and transformation of murine fibroblasts.
AB  - Emerging evidence suggests involvement of the ephrin/Eph receptor system in
      tumourigenesis. Research on this new role has centred on the contribution of Eph
      receptors. In contrast, we focused on the elucidation of the role of ephrins,
      specifically ephrin A5. Results indicated an increase in invasive potential of
      ephrin A5-expressing murine fibroblasts, which was abolished by addition of a Src
      family kinase inhibitor. Furthermore, anchorage-independent growth was increased
      in ephrin A5-expressing cells. Stimulation with EphA5-Fc receptor increased
      colony size, but not colony number in ephrin A5 transfectants. Moreover, we
      observed morphogenetic transformation of ephrin A5-expressing 3T3 cells into a
      branching network when plated onto Matrigel. This behaviour was specific to
      ephrin A5 transfectants, as 3T3 cells expressing ephrin B1 displayed a phenotype
      similar to control 3T3 cells. We conclude that ectopic expression of ephrin A5 in
      murine fibroblasts elevates oncogenic potential, including increased invasive
      behaviour, anchorage-independent growth, and morphological transformation.

PMID- 17022941
TI  - Correct and incorrect nucleotide incorporation pathways in DNA polymerase beta.
AB  - Tracking the structural and energetic changes in the pathways of DNA replication
      and repair is central to the understanding of these important processes. Here we
      report favorable mechanisms of the polymerase-catalyzed phosphoryl transfer
      reactions corresponding to correct and incorrect nucleotide incorporations in the
      DNA by using a novel protocol involving energy minimizations, dynamics
      simulations, quasi-harmonic free energy calculations, and mixed quantum
      mechanics/molecular mechanics dynamics simulations. Though the pathway proposed
      may not be unique and invites variations, geometric and energetic arguments
      support the series of transient intermediates in the phosphoryl transfer pathways
      uncovered here for both the G:C and G:A systems involving a Grotthuss hopping
      mechanism of proton transfer between water molecules and the three conserved
      aspartate residues in pol beta's active-site. In the G:C system, the rate
      limiting step is the initial proton hop with a free energy of activation of at
      least 17 kcal/mol, which corresponds closely to measured k(pol) values. Fidelity
      discrimination in pol beta can be explained by a significant loss of stability of
      the closed ternary complex of the enzyme in the G:A system and much higher
      activation energy of the initial step of nucleophilic attack, namely
      deprotonation of terminal DNA primer O3'H group. Thus, subtle differences in the
      enzyme active-site between matched and mismatched base pairs generate significant
      differences in catalytic performance.

PMID- 17022943
TI  - Adrenomedullin in adipocyte differentiation of human mesenchymal stem cells.
AB  - Expression of adrenomedullin (AM), a potent vasodilator peptide, was studied
      during adipocyte differentiation of human mesenchymal stem cells (hMSCs).
      Immunoreactive AM levels in the medium were increased at day 4 and 8 of the
      adipocyte differentiation. Northern blot analysis showed increased expression of
      AM mRNA in hMSCs-derived adipocytes at day 4, 8, 12, and 18. Transient
      transfection assay showed that the promoter activity was higher in hMSCs-derived
      adipocytes than in hMSCs, when cells were transfected with plasmids containing a
      cis-acting region (-70/-29) of the human AM gene. Electrophoretic mobility shift
      assay showed that specific bands bound to the region (-70/-29) in hMSCs-derived
      adipocytes but not in hMSCs, and were abolished by the stimulatory protein 1
      (Sp1) antibody. The present study has shown that AM expression is up-regulated
      during adipocyte differentiation of hMSCs probably via the interaction between
      Sp1 or Sp1-related factor(s) and the AM promoter region (-70/-29).

PMID- 17022944
TI  - Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated
      by adiponectin and fenofibric acid in hepatocytes in vitro.
AB  - Adiponectin protects the liver from steatosis caused by obesity or alcohol and
      therefore the influence of adiponectin on human hepatocytes was analyzed.
      GeneChip experiments indicated that recombinant adiponectin downregulates
      aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR
      and immunoblot. AOX1 is a xenobiotic metabolizing protein and produces reactive
      oxygen species (ROS), that promote cell damage and fibrogenesis. Adiponectin and
      fenofibric acid activate peroxisome proliferator-activated receptor-alpha (PPAR
      alpha) and both suppress AOX1 protein and this is blocked by the PPAR-alpha
      antagonist RU486. Obesity is associated with low adiponectin, reduced hepatic
      PPAR-alpha activity and fatty liver, and AOX1 was found induced in the liver of
      rats on a high-fat diet when compared to controls. Free fatty acids and leptin,
      that are elevated in obesity, failed to upregulate AOX1 in vitro. The current
      data indicate that adiponectin reduces AOX1 by activating PPAR-alpha whereas
      fatty liver disease is associated with elevated hepatic AOX1. High AOX1 may be
      associated with higher ROS well described to induce fibrogenesis in liver tissue
      but may also influence drug metabolism and activity.

PMID- 17022945
TI  - Characterization of the type 3 fimbriae with different MrkD adhesins: possible
      role of the MrkD containing an RGD motif.
AB  - Four novel mrkD alleles namely mrkD(V1), mrkD(V2), mrkD(V3), and mrkD(V4) were
      identified in seventeen Klebsiella pneumoniae meningitis strains using PCR-RFLP
      and sequence determination. Comparative analysis revealed a most variable region
      containing an RGD motif in the receptor domain of MrkD(V3). In order to determine
      if the sequence confers the K. pneumoniae mrkD(V3) the highest level of the
      fimbrial activity, a type 3 fimbriae display system was constructed in
      Escherichia coli. The E. coli JM109[pmrkABCD(V3)F] displaying meshwork-like
      fimbriae also had the most fimbrial activity, supporting a possible role of the
      varied sequences. In a dose-dependent manner, the GRGDSP hexapeptide appeared to
      inhibit the adhesion of the E. coli JM109[pmrkABCD(V3)F] to HCT-8, an ileocecal
      epithelial cell line. In addition, the adhesion activity was reduced by the
      addition of anti-alpha5beta1 integrin monoclonal antibody, indicating that the
      RGD containing region in MrkD(V3) is responsible for the binding of type 3
      fimbriae to integrin.

PMID- 17022946
TI  - Characterization of the desensitization properties of five dopamine receptor
      subtypes and alternatively spliced variants of dopamine D2 and D4 receptors.
AB  - Proper regulation of brain dopaminergic activity is essential for maintaining
      normal mental functions. In this study, the regulatory properties of five
      different dopamine receptor subtypes and alternative splicing variants of
      dopamine D2 and D4 were examined. The stimulation of D1R, D2R, D5R but not D3R,
      D4R caused the robust translocation of beta-arrestin to the plasma membrane. When
      D1R or D3R were co-expressed with D2R, D1R significantly inhibited the
      sequestration of D2R, suggesting that the inhibitory effects of D1R on the D2R
      sequestration could explain the synergistic activity between two receptors. The
      sequestration of alternatively spliced isoforms of D2R was differently regulated
      by GRKs and beta-arrestins. Three alternative splicing variants of D4R produced a
      similar level of beta-arrestin translocation, and the studies with the deletion
      mutants of D4R within the third cytoplasmic loop revealed that the regions
      containing the SH3-binding domains are responsible for the beta-arrestin
      translocation.

PMID- 17022947
TI  - Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis.
AB  - Osteopetrotic mice lacking functional macrophage-colony stimulating factor (M
      CSF) recover with ageing, suggesting that alternative osteoclastogenesis pathways
      exist. Hepatocyte growth factor (HGF) and M-CSF signal through tyrosine kinase
      receptors and phosphorylate common transducers and effectors such as Src, Grb2,
      and PI3-Kinase. HGF is known to play a role in osteoclast formation, and in this
      study we have determined whether HGF could replace M-CSF to support human
      osteoclastogenesis. We found that the HGF receptor, c-Met, is expressed by the
      CD14(+) monocyte fraction of human peripheral blood mononuclear cells (PBMC). HGF
      was able to support monocyte-osteoclast differentiation in the presence of
      receptor activator for nuclear factor kappaB ligand as evidenced by the formation
      of numerous multinucleated tartrate-resistant acid phosphatase and vitronectin
      receptor positive cells which formed F-actin rings and were capable of lacunar
      resorption. The addition of a neutralising antibody to M-CSF did not inhibit
      osteoclast differentiation. HGF is a well-established survival factor and
      viability assays and live/dead staining showed that it promoted the survival and
      proliferation of monocytes and osteoclasts in a manner similar to M-CSF. Our
      findings indicate that HGF can substitute for M-CSF to support human osteoclast
      formation.

PMID- 17022948
TI  - Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF
      expression and phosphorylation of CREB.
AB  - Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao
      san, which has been used to effectively manage stress and depression-related
      disorders in China. Curcumin is the active component of curcuma longa, and its
      antidepressant effects were described in our prior studies in mouse models of
      behavioral despair. We hypothesized that curcumin may also alleviate stress
      induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis
      dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5
      and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of
      depression in rats and examined what its molecular targets may be. We found that
      subjecting animals to the chronic stress protocol for 20days resulted in
      performance deficits in the shuttle-box task and several physiological effects,
      such as an abnormal adrenal gland weight to body weight (AG/B) ratio and
      increased thickness of the adrenal cortex as well as elevated serum
      corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression.
      These changes were reversed by chronic curcumin administration (5 or 10 mg/kg,
      p.o.). In addition, we also found that the chronic stress procedure induced a
      down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and
      reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB)
      to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed
      rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were
      also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These
      results provide compelling evidence that the behavioral effects of curcumin in
      chronically stressed animals, and by extension humans, may be related to their
      modulating effects on the HPA axis and neurotrophin factor expressions.

PMID- 17022949
TI  - Brain distribution of cytokine mRNA induced by systemic administration of
      interleukin-1beta or tumor necrosis factor alpha.
AB  - Brain cytokine mRNA levels are impacted by systemic cytokines. For example,
      systemic interleukin-1beta (IL1beta) increases brain IL1beta mRNA;
      subdiaphragmatic vagotomy blocks this effect. To localize which brain regions
      respond to intraperitoneal cytokines, we measured mRNA levels in selected brain
      regions for a variety of cytokines and growth factors, IL1beta, TNFalpha,
      interleukin-6 (IL-6), interleukin-10 (IL10), nerve growth factor (NGF) and brain
      derived neurotrophic factor (BDNF). Relative to saline administration, IL1beta
      increased IL1beta, TNFalpha and IL6 mRNAs in the nucleus tractus solitarius
      (NTS), hypothalamus, hippocampus and somatosensory cortex (SSctx), but did not
      induce any changes in IL10. TNFalpha also increased TNFalpha and IL1beta mRNAs in
      the hypothalamus, hippocampus and SSctx. TNFalpha increased TNFalpha, IL1beta and
      IL10 mRNAs in the NTS, but did not induce any changes in IL-6 mRNA. In the
      amygdala, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNAs. In the
      insular cortex, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNA.
      TNFalpha administration increased NGF mRNA in the SSctx but decreased NGF and
      BDNF mRNA levels in the insular cortex. Both IL1beta and TNFalpha decreased BDNF
      mRNA in the amygdala. We also verified the IL1beta-induced increases in TNFalpha
      mRNA within the NTS using in situ hybridization. These results support the
      hypothesis that somnogenic doses of IL1beta and TNFalpha enhance their own mRNA
      levels as well as affect mRNA levels for other sleep-promoting substances.

PMID- 17022950
TI  - Increased nitric oxide levels and nitric oxide synthase isoform expression in the
      cerebellum of the taiep rat during its severe demyelination stage.
AB  - We have previously reported progressive reactive astrocytes in the cerebellum of
      taiep rats, one of the most regions affected by demyelination, and activation of
      cerebellar glial cells in vitro. Based on the hypothesis that activated glial
      cells produce high levels of reactive nitrogen intermediates, we assessed the
      production of nitric oxide (NO) and the expression of the three NO synthases
      (NOS) in the cerebellum of 6-month-old taiep rats. A significant 40% increase of
      NO levels was measured in taiep rats when compared with controls. The protein and
      mRNA levels of the three NOS isoforms were also significantly increased. In
      contrast to controls, immunostaining assays against nNOS or iNOS showed an
      increased number of immunoreactive glial cells in the granular layer (nNOS) and
      Purkinje layer (iNOS) of cerebellum of taiep rats. Microglia-macrophages and both
      CD4- and CD8-immunoreactive cells were observed in cerebellar white matter of
      taiep rats only, thus suggesting other possible cell sources of those NOSs.
      Differences in the cellular location for eNOS immunoreactivity were not observed.
      The enhanced levels of NO, NOS proteins, mRNAs, and NOS immunoreactivities in
      glial cells and microglia strongly suggest glial activation together with the
      professional immune cells can aggravate the demyelination of aged taiep rats.

PMID- 17022951
TI  - Postnatal onset cortical dysplasia associated with infarction of white matter.
AB  - On MRI at 35 weeks of a boy born at 25 weeks, focal disorganization of the cortex
      was observed near a frontal venous infarct developed in the first week.
      Disruption of the final steps of cell migration, injury to the subplate and/or
      disruption of corticospinal axons are possible mechanisms behind it. Preterms
      with white matter lesions at or below 25 weeks postconceptional age should be
      scrutinized for cortical dysplasia.

PMID- 17022952
TI  - Ultraviolet irradiation-induced apoptosis does not trigger nuclear fragmentation
      but translocation of chromatin from nucleus into cytoplasm in the microglial cell
      line, BV-2.
AB  - Chromatin condensation, decrease of nuclear volume, and nuclear fragmentation are
      key features of apoptosis (programmed cell death) in many eukaryotic cells. How
      chromatin is redistributed in a continuously shrinking nucleus is an intriguing
      question. To evaluate this interesting spatial problem, we studied the
      ultrastructural distribution of chromatin in distinct stages of apoptosis using
      the microglial cell-line, BV-2, as a model and UV irradiation as a trigger of
      apoptosis. During apoptosis, condensed chromatin accumulated initially at the
      nuclear periphery and, subsequently, occupied almost the entire nucleus.
      Surprisingly, nuclei did not fragmentize, but apoptotic cells showed condensed
      chromatin in the nucleus as well as in the nucleus-attached cytoplasm. During
      apoptosis, the nuclear envelope dilated and decreased in extension by formation
      of numerous electron lucent vesicles, which accumulated in the cytoplasm.
      Furthermore, we observed in BV-2 cells well-known apoptotic features, like
      increased caspase-3/7 activity and annexin V labeling, as well as a sequence of
      cell morphological alterations, including cell shrinkage, zeiosis, and formation
      of apoptotic bodies. Thus, our findings suggest that UV-induced chromatin
      degradation is not restricted to the nucleus but may also take place in the
      cytoplasm in BV-2 cells.

PMID- 17022953
TI  - G501C polymorphism of oxidized LDL receptor gene (OLR1) and ischemic stroke.
AB  - The human lectin-like oxidized low-density lipoprotein receptor 1 (OLR1/LOX-1) is
      the major endothelial scavenger receptor against oxidized low-density lipoprotein
      (Ox-LDL), which has been implicated in the pathogenesis of atherosclerosis. We
      investigated the G501C mutation in the OLR1 gene in 235 Japanese patients with
      ischemic cerebrovascular disease (CVD) and 274 age- and sex-matched healthy
      controls using single nucleotide primer extension analysis (SNuPe). There was no
      significant difference in the polymorphism between patients with ischemic CVD and
      controls (GC+CC versus GG, p=0.48). The C allele was not significantly different
      between the patients and controls (C versus G, p=0.91). Our results show that the
      OLR1 gene polymorphism has little effect on an increased risk for ischemic CVD in
      the Japanese population.

PMID- 17022954
TI  - Oddball and incongruity effects during Stroop task performance: a comparative
      fMRI study on selective attention.
AB  - The aim of this fMRI study was to investigate and compare the neural mechanisms
      of selective attention during two different operationalizations of competition
      between task-relevant and task-irrelevant information: Stroop-incongruity and
      oddballs. For this purpose, we employed a Stroop-like oddball task in which
      subjects responded to the font size of presented word stimuli. Stroop-incongruity
      was created by (response-)incongruent word information while oddballs comprised
      low-frequency events in a task-irrelevant, unattended dimension. Thereby, in
      order to elucidate the influence of processing domain from which competition
      emanates, oddball conditions were created in two different attribute dimensions,
      color and word meaning. Either oddball condition was expected to evoke an
      orienting response, which participants would have to override in order to
      maintain adequate performance. Incongruent Stroop trials were expected to produce
      Stroop-interference so that subjects would have to override the predominant
      tendency to read and respond to word meaning. All competition conditions
      exhibited significantly prolonged reaction times compared to control trials,
      demonstrating that our experimental manipulation was indeed effective. fMRI data
      analyses delineated two discriminative components of competition: one component
      mainly related to motor preparation and another, primarily attentional component.
      Regarding the first, Stroop-interference increased activation mainly in regions
      implicated in motor control or response preparation. Regarding the second, Word
      oddballs increased activation in a frontoparietal "attention network".
      Furthermore, Word-oddballs and Color-oddballs exhibited striking activation
      overlap mainly in prefrontal regions but also in posterior processing areas.
      Here, the data emphasized a prominent role of posterior lateral PFC in
      implementing top-down attentional control.

PMID- 17022955
TI  - Nogo A, B and C expression in schizophrenia, depression and bipolar frontal
      cortex, and correlation of Nogo expression with CAA/TATC polymorphism in 3'-UTR.
AB  - Schizophrenia may result from altered gene expression leading to abnormal
      neurodevelopment. In a search for genes with altered expression in schizophrenia,
      our previous work on human frontal cerebral cortex found the mRNA of Nogo, a
      myelin-associated protein which inhibits the outgrowth of neurites and nerve
      terminals, to be overexpressed in schizophrenia. Because those earlier results
      did not examine tissues for the separate Nogo A, B and C isoforms from age- and
      sex-matched individuals, we repeated the study for all three isoforms, using a
      new set of tissues from matched individuals, and using the more accurate method
      of quantitative real-time PCR (polymerase chain reaction). We found Nogo C to be
      overexpressed by 26% in the schizophrenia tissues, which is in accordance with
      our earlier results. The expression of Nogo B was statistically significantly
      reduced by 17% in the frontal cortices from individuals who had been diagnosed as
      having had severe depression. Furthermore, we show that there is a direct
      correlation between the expression of Nogo A and C and the presence of alleles
      with a CAA insert, irrespective of disease status. While upregulation of Nogo C
      expression may play a role in schizophrenia, altered Nogo B may contribute to the
      clinical condition of depression. Nogo A showed a statistically non-significant
      increase in expression in schizophrenia.

PMID- 17022956
TI  - Preparation of ethylenediamine-anchored cellulose and determination of
      thermochemical data for the interaction between cations and basic centers at the
      solid/liquid interface.
AB  - Cellulose was first modified with thionyl chloride, giving 99% substitution at
      C6, and then reacted with ethylene-1,2-diamine to produce 6-(2'-aminoethylamino)
      6-deoxy-cellulose. From the 8.5% of nitrogen incorporated in the polysaccharide
      backbone, the amount of ethylene-1,2-diamine anchored per gram of modified
      cellulose was determined to be 3.03+/-0.01mmol. This chemically immobilized
      surface was characterized by FTIR, TG, (13)C NMR, and SEM techniques. The
      available basic nitrogen centers covalently bonded to the biopolymer skeleton
      were studied for copper, cobalt, nickel, and zinc adsorption from aqueous
      solutions and the respective thermal adsorption effects were determined by
      calorimetric titration. The ability to adsorb cations gave a capacity order of
      Co(2+)>Cu(2+)>Zn(2+)>Ni(2+) with affinities of 1.91+/-0.07, 1.32+/-0.07, 1.31+/
      0.02, and 1.08+/-0.04mmol/g, respectively. The net thermal effects obtained from
      calorimetric titration measurements were adjusted to a modified Langmuir equation
      and the enthalpy of the interaction was calculated to give the following
      exothermic values: -20.8+/-0.05, -11.72+/-0.03, -7.32+/-0.01, and -6.27+/
      0.02kJ/mol for Co(2+), Cu(2+), Zn(2+), and Ni(2+), respectively. With the
      exception of the entropic value for copper, the other thermodynamic data for
      these systems are favorable for cation adsorption from aqueous solutions at the
      solid/liquid interface, suggesting the use of this anchored biopolymer for cation
      removal from the environment.

PMID- 17022957
TI  - Anthracycline glycosides of 2,6-dideoxy-2-fluoro-alpha-L-talopyranose.
AB  - The methyl beta-glycoside of the title sugar, obtained from 2-deoxy-2-fluoro-beta
      D-glucopyranose tetraacetate by a sequence with detailed characterization of all
      intermediates, was converted by acetolysis-bromination into 3,4-di-O-acetyl-2,6
      dideoxy-2-fluoro-alpha-L-talopyranosyl bromide, coupling of which with (7S,9S)-4
      demethoxydaunomycinone afforded the 3,4-diacetate of 4-demethoxy-9-O-(2,6-dideoxy
      2-fluoro-alpha-L-talopyranosyl)daunomycinone (19). The antitumor-active 19 was
      converted by way of its 14-bromo derivative into the 14-hydroxy analogue, the
      antitumor-active 4-demethoxyadriamycinone glycoside 21.

PMID- 17022958
TI  - Catecholamines and development of cardiac pacemaking: an intrinsically intimate
      relationship.
AB  - A generation ago, a melding of imagination and experimental evidence led to the
      hypothesis that catecholamines were essential in establishing basal cardiac
      pacemaking rhythm. Subsequent discoveries of depolarizing "pacemaker" currents
      and viable adult catecholamine-deficient animals raised serious doubts about the
      necessity of catecholamines in pacemaking. However, the findings that
      catecholamines are produced in pacemaking regions prior to innervation, and that
      they are required for embryonic survival during a defined "critical period" of
      embryonic development have revitalized the original hypothesis. Recent results
      have further suggested that intrinsic cardiac adrenergic cells can differentiate
      into pacemaking myocytes, and that protein kinase A, a prominent downstream
      mediator of beta-adrenergic signaling, is required for pacemaking activity. Here,
      we discuss how catecholamines and the intrinsic cardiac adrenergic cells that
      produce them may influence ontological development of cardiac pacemaking.

PMID- 17022959
TI  - Stability of IMMULITE 2000 plasma NT-proBNP in tubes with separator gel stored at
      room temperature.

PMID- 17022960
TI  - FGF8/17/18 functions together with FGF9/16/20 during formation of the notochord
      in Ciona embryos.
AB  - Fibroblast growth factor (FGF) signalling has been implicated in the generation
      of mesoderm and neural fates in chordate embryos including ascidians and
      vertebrates. In Ciona, FGF9/16/20 has been implicated in both of these processes.
      However, in FGF9/16/20 knockdown embryos, notochord fate recovers during later
      development. It is thus not clear if FGF signalling is an essential requirement
      for notochord specification in Ciona embryos. We show that FGF-MEK-ERK signals
      act during two distinct phases to establish notochord fate. During the first
      phase, FGF signalling is required during an asymmetric cell division to promote
      notochord at the expense of neural identity. Consistently, ERK1/2 is specifically
      activated in the notochord precursors following this cell division. Sustained
      activation of ERK1/2 is then required to maintain notochord fate. We demonstrate
      that FGF9/16/20 acts solely during the initial induction step and that,
      subsequently, FGF8/17/18 together with FGF9/16/20 is involved in the following
      maintenance step. These results together with others' show that the formation of
      a large part of the mesoderm cell types in ascidian larvae is dependent on
      signalling events involving FGF ligands.

PMID- 17022961
TI  - Partial rescue of defects in Cited2-deficient embryos by HIF-1alpha
      heterozygosity.
AB  - Hypoxia inducible factor-1 (HIF-1) initiates key cellular and tissue responses to
      physiological and pathological hypoxia. Evidence from in vitro and structural
      analyses supports a critical role for Cited2 in down-regulating HIF-1-mediated
      transcription by competing for binding with oxygen-sensitive HIF-1alpha to
      transcriptional co-activators CBP/p300. We previously detected elevated
      expression of HIF-1 target genes in Cited2(-/-) embryonic hearts, indicating that
      Cited2 inhibits HIF-1 transactivation in vivo. In this study, we show for the
      first time that highly hypoxic cardiac regions in mouse embryos corresponded to
      the sites of defects in Cited2(-/-) embryos and that defects of the outflow
      tract, interventricular septum, cardiac vasculature, and hyposplenia were largely
      rescued by HIF-1alpha haploinsufficiency. The hypoxia of the outflow tract and
      interventricular septum peaked at E13.5 and dissipated by E15.5 in wild-type
      hearts, but persisted in E15.5 Cited2(-/-) hearts. The persistent hypoxia and
      abnormal vasculature in the myocardium of interventricular septum in E15.5
      Cited2(-/-) hearts were rescued with decreased HIF-1alpha gene dosage.
      Accordingly, mRNA levels of HIF-1-responsive genes were reduced in Cited2(-/-)
      embryonic hearts by HIF-1alpha heterozygosity. These findings suggest that a
      precise level of HIF-1 transcriptional activity critical for normal development
      is triggered by differential hypoxia and regulated through feedback inhibition by
      Cited2.

PMID- 17022962
TI  - Branching morphogenesis of the ureteric epithelium during kidney development is
      coordinated by the opposing functions of GDNF and Sprouty1.
AB  - Branching of ureteric bud-derived epithelial tubes is a key morphogenetic process
      that shapes development of the kidney. Glial cell line-derived neurotrophic
      factor (GDNF) initiates ureteric bud formation and promotes subsequent branching
      morphogenesis. Exactly how GDNF coordinates branching morphogenesis is unclear.
      Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty1
      (Spry1) results in irregular branching morphogenesis characterized by both
      increased number and size of ureteric bud tips. Deletion of Spry1 specifically in
      the epithelium is associated with increased epithelial Wnt11 expression as well
      as increased mesenchymal Gdnf expression. We propose that Spry1 regulates a
      Gdnf/Ret/Wnt11-positive feedback loop that coordinates mesenchymal-epithelial
      dialogue during branching morphogenesis. Genetic experiments indicate that the
      positive (GDNF) and inhibitory (Sprouty1) signals have to be finely balanced
      throughout renal development to prevent hypoplasia or cystic hyperplasia.
      Epithelial cysts develop in Spry1-deficient kidneys that share several molecular
      characteristics with those observed in human disease, suggesting that Spry1 null
      mice may be useful animal models for cystic hyperplasia.

PMID- 17022964
TI  - Cardiac function and remodeling is attenuated in transgenic rats expressing the
      human kallikrein-1 gene after myocardial infarction.
AB  - Bradykinin coronary outflow, left ventricular performance and left ventricular
      dimensions of transgenic rats harboring the human tissue kallikrein-1 gene
      TGR(hKLK1) were investigated under basal and ischemic conditions. Bradykinin
      content in the coronary outflow of buffer-perfused, isolated hearts of controls
      and TGR(hKLK1) was measured by specific radioimmunoassay before and after global
      ischemia. Left ventricular function and left ventricular dimensions were
      determined in vivo using a tip catheter and echocardiography 6 days and 3 weeks
      after induction of myocardial infarction. Left ventricular type I collagen mRNA
      expression was analyzed by RNase protection assay. Compared to controls, basal
      bradykinin outflow was 3.5 fold increased in TGR(hKLK1). Ischemia induced an
      increase of bradykinin coronary outflow in controls but did not induce a further
      increase in TGR(hKLK1). However, despite similar unchanged infarction sizes, left
      ventricular function and remodeling improved in TGR(hKLK1) after myocardial
      infarction, indicated by an increase in left ventricular pressure (+34%; P<0.05),
      contractility (dp/dt max. +25%; P<0.05), and in ejection fraction (+20%; P<0.05)
      as well as by a reduction in left ventricular enddiastolic pressure (-49%,
      P<0.05), left ventricular enddiastolic diameter (-20%, P<0.05), and collagen mRNA
      expression (-15%, P<0.05) compared to controls. A chronically activated
      transgenic kallikrein kinin system with expression of human kallikrein-1 gene
      counteracts the progression of left ventricular contractile dysfunction after
      experimental myocardial infarction. Further studies have to show whether these
      results can be caused by other therapeutically options. Long acting bradykinin
      receptor agonists might be an alternative option to improve ischemic heart
      disease.

PMID- 17022963
TI  - Selective degradation of transcripts during meiotic maturation of mouse oocytes.
AB  - There is massive destruction of transcripts during the maturation of mouse
      oocytes. The objective of this project was to identify and characterize the
      transcripts that are degraded versus those that are stable during the
      transcriptionally silent germinal vesicle (GV)-stage to metaphase II (MII)-stage
      transition using a microarray approach. A system for oocyte transcript
      amplification using both internal and 3'-poly(A) priming was utilized to minimize
      the impact of complex variations in transcript polyadenylation prevalent during
      this transition. Transcripts were identified and quantified using the Affymetrix
      Mouse Genome 430 v2.0 GeneChip. The significantly changed and stable transcripts
      were analyzed using Ingenuity Pathways Analysis and GenMAPP/MAPPFinder to
      characterize the biological themes underlying global changes in oocyte
      transcripts during maturation. It was concluded that the destruction of
      transcripts during the GV to MII transition is a selective rather than
      promiscuous process in mouse oocytes. In general, transcripts involved in
      processes that are associated with meiotic arrest at the GV-stage and the
      progression of oocyte maturation, such as oxidative phosphorylation, energy
      production, and protein synthesis and metabolism, were dramatically degraded. In
      contrast, transcripts encoding participants in signaling pathways essential for
      maintaining the unique characteristics of the MII-arrested oocyte, such as those
      involved in protein kinase pathways, were the most prominent among the stable
      transcripts.

PMID- 17022965
TI  - Possible expression of a particular gamma-aminobutyric acid transporter isoform
      responsive to upregulation by hyperosmolarity in rat calvarial osteoblasts.
AB  - Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the brain,
      but widely distributed in different peripheral organs. We have previously shown
      the functional expression of GABA(B) receptors required for GABAergic signal
      input by cultured rat calvarial osteoblasts. This study focused on the possible
      functional expression of the machinery required for GABAergic signal termination
      such as GABA transporters. In rat calvarial osteoblasts cultured for 7 days,
      [(3)H]GABA accumulation was observed in a temperature-, sodium- and chloride
      dependent manner, consisting of a single component with a K(m) value of 789.6+/
      9.0 microM and a V(max) value of 4.4+/-0.1 nmol/min/mg protein, respectively.
      Both nipecotic and L-2,4-diaminobutyric acids significantly inhibited [(3)H]GABA
      accumulation in a concentration-dependent manner. Constitutive expression was
      seen with mRNA for the betaine/GABA transporter-1 (BGT-1) and taurine transporter
      (TauT), while hyperosmotic cultivation led to significant increases in both
      [(3)H]GABA accumulation and BGT-1 mRNA expression without affecting TauT mRNA
      expression. Highly immunoreactive cells were detected for the BGT-1 isoform at
      the surface of trabecular bone of neonatal rat tibias. Sustained exposure to GABA
      significantly inhibited alkaline phosphatase (ALP) activity, but not cellular
      viability, at concentrations above 0.1 mM in osteoblasts cultured for 3 to 28
      days. Nipecotic acid not only decreased ALP activity alone, but also further
      decreased ALP activity in osteoblasts cultured in the presence of GABA. These
      results suggest that the BGT-1 isoform may be functionally expressed by rat
      calvarial osteoblasts to play a hitherto unidentified role in mechanisms
      underlying hyperosmotic regulation of osteoblastogenesis.

PMID- 17022966
TI  - The suppressant effect of GEA3162 on spontaneous serotonin release from human
      colonic mucosa in vitro.
AB  - The effect of a lipophilic nitric oxide (NO)-releasing compound 5-amino-3-(3,4
      dichlorophenyl) 1,2,3,4-oxatriazolium (GEA3162) on the spontaneous release of 5
      hydroxytryptamine (5-HT) from human colonic mucosa was investigated in vitro. In
      the presence of tetrodotoxin, spontaneous outflow of 5-HT from the human colonic
      mucosa was measured by high-performance liquid chromatography with
      electrochemical detection. GEA3162 concentration-dependently suppressed the 5-HT
      outflow, but neither the NO-activated soluble guanylate cyclase inhibitor 1H
      [1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) nor peroxynitrite scavenger
      ebselen affected the suppressant effect of GEA3162. Moreover, neither the L-type
      calcium channel blocker nicardipine, NO synthase inhibitor l-N(G)-nitroarginine
      methyl ester nor guanylate cyclase activator guanylin affected the spontaneous 5
      HT outflow. These results indicate that human colonic mucosa is capable of
      eliciting tetrodotoxin-resistant and nicardipine-insensitive 5-HT release, and
      that GEA3162 can suppress the 5-HT release via an action on colonic mucosa
      through mechanism independent of ODQ-sensitive cyclic GMP system or peroxynitrite
      generation.

PMID- 17022967
TI  - Influence of ATP-sensitive potassium channels on lithium state-dependent memory
      of passive avoidance in mice.
AB  - The effects of ATP-sensitive potassium channels on lithium induced state
      dependent memory of passive avoidance task were examined in mice. The pre
      training (5 mg/kg) and pre-test (5 mg/kg) injection of lithium impaired memory
      retrieval on the test day. Impairment of pre-training lithium was restored by pre
      test administration of lithium (5 mg/kg), diazoxide, an ATP-sensitive potassium
      channel opener, (15, 30 and 60 mg/kg) or glibenclamide, an ATP-sensitive
      potassium channel blocker, (6 and 18 mg/kg). Pre-test administration of inactive
      doses of lithium (2.5 and 10 mg/kg) plus lower and inactive dose of glibenclamide
      (2 mg/kg) or diazoxide (1.5 mg/kg) also reversed the amnesia induced by pre
      training lithium (5 mg/kg). In conclusion, the ATP-sensitive potassium channel
      opener or blocker not only mimicked the effect of lithium in state-dependent
      learning in the absence of lithium on the test day, but also potentiated the
      effect of low dose of lithium in restoration of memory. Therefore, ATP-sensitive
      potassium channels may have a modulatory influence on lithium response.

PMID- 17022968
TI  - Baclofen-induced suppression of alcohol deprivation effect in Sardinian alcohol
      preferring (sP) rats exposed to different alcohol concentrations.
AB  - This study investigated the effect of the gamma-aminobutyric acid(B) (GABA(B))
      receptor agonist, baclofen, on alcohol deprivation effect (the transient increase
      in alcohol intake occurring after a period of alcohol abstinence) in Sardinian
      alcohol-preferring (sP) rats exposed to 4 bottles containing water and 10%, 20%,
      and 30% (v/v) alcohol, respectively. Acute administration of baclofen (1 mg/kg,
      i.p.) suppressed both aspects of alcohol deprivation effect: the extra-intake of
      alcohol and the selection of the highest concentrated alcohol solution. These
      results suggest that the GABA(B) receptor is part of the neural substrate
      mediating alcohol deprivation in sP rats.

PMID- 17022969
TI  - Involvement of 5-hydroxytryptamine1A receptors in Delta9-tetrahydrocannabinol
      induced catalepsy-like immobilization in mice.
AB  - The present study investigated the involvement of 5-hydroxytryptamine(1A) (5
      HT(1A)) receptors in Delta(9)-tetrahydrocannabinol (THC)-induced catalepsy-like
      immobilization in mice. THC (10 mg/kg, i.p.) induced catalepsy-like
      immobilization but had no effect on motor coordination in the rota-rod test. The
      selective cannabinoid CB(1) receptor antagonist rimonabant (3 mg/kg, i.p.)
      completely antagonized THC-induced catalepsy-like immobilization. The 5-HT(1A)/5
      HT(7) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 0.3
      and 1 mg/kg, i.p.) and 5-HT(1A) receptor partial agonist buspirone (0.06 and 0.1
      mg/kg, i.p.) inhibited this THC-induced catalepsy-like immobilization. Moreover,
      the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl) cyclohezane carboxamide dihydrochloride
      (WAY100635; 0.3 or 1 mg/kg, i.p.) reversed the inhibition of THC-induced
      catalepsy-like immobilization by 8-OH-DPAT (1 mg/kg) or buspirone (0.06 mg/kg).
      In contrast, the selective 5-HT(7) receptor antagonist (R)-3-[2-[2-(4
      methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970)
      had no effect on this inhibitory effect of 8-OH-DPAT. On the other hand,
      WAY100635 (0.3 and 1 mg/kg, i.p.) enhanced the catalepsy-like immobilization
      induced by THC (6 mg/kg, i.p.). These findings suggest that the 5-HT(1A)
      receptors are involved in THC-induced catalepsy-like immobilization.

PMID- 17022970
TI  - Effects of genetic background and null mutation of 5-HT1A receptors on basal and
      stress-induced body temperature: modulation by serotonergic and GABAA-ergic
      drugs.
AB  - The stress-induced hyperthermia procedure, in which effects of drugs on basal
      (T(1)) and stress-induced body temperature (T(2)) are measured, predicts
      anxiolytic drug effect. Serotonergic drugs alter these responses and here, we
      studied the role of 5-HT(1A) receptors in stress-induced hyperthermia by using 5
      HT(1A) receptor knockout mice. Three strains (129/Sv, Swiss Webster and C57Bl6)
      were used because genetic background can significantly modulate the null
      phenotype. We found that GABA-ergic drugs with an anxiolytic profile and
      stimulate alpha(2) subunit containing GABA(A) receptors, including diazepam and
      L838,417, result in reduced DeltaT (DeltaT=T(2)-T(1)). The alpha(1) subunit
      containing GABA(A) receptor was found to be primarily involved in regulation of
      basal body temperature T(1) and its stimulation can induce hypothermia. In
      addition, stimulation of 5-HT(1A) receptors by buspirone results in a reduced
      DeltaT, while stimulation of 5-HT(7) receptors primarily results in hypothermia.
      The null mutation of 5-HT(1A) receptors resulted in differences in drug
      sensitivity that was further modulated by the genetic background. In particular,
      the null mutation on the SW and C57Bl6 backgrounds resulted in differential
      diazepam/L838,417 and 5-CT responses respectively. This indicates an interaction
      between the 5-HT(1A) receptor and genetic background and demonstrates the
      importance of selecting the background strain in a receptor knockout model.

PMID- 17022971
TI  - Immunohistochemical and ultrastructural analysis of a poorly differentiated
      pediatric age Sertoli-Leydig cell tumor.
AB  - Ovarian Sertoli-Leydig cell tumors (SLCT) are rare in young women. They are
      divided into six categories based on the degree of differentiation and the
      presence of heterologous elements. Less than 15% of these tumors are poorly
      differentiated. A 14-year-old obese African-American girl presented with
      amenorrhea, progressive abdominal pain, and increasing abdominal girth. Pelvic CT
      revealed a 10 x 9 x 9 cm right adnexal mass which was resected successfully. The
      gross appearance was dark tan and red with central hemorrhage and necrosis.
      Microscopically, this was poorly differentiated with compact aggregates of
      moderate size oval to elongated cells separated by zones of edematous stroma
      containing scattered spindle shape cells. Areas of ill-formed tubules and
      primitive cords were present. Clusters of Leydig cells were observed. The oval
      and spindle cells showed multiple mitoses and were diffusely positive for inhibin
      and patchy but strong positivity for calretinin. Both preoperative and
      postoperative studies revealed no metastases. Serum alpha-fetal protein (AFP),
      androgen, and dihydroepiandrosterone sulfate (DHEA-S) were elevated.

PMID- 17022972
TI  - Bone morphogenetic protein-2 promotes the haptotactic migration of murine
      osteoblastic and osteosarcoma cells by enhancing incorporation of integrin beta1
      into lipid rafts.
AB  - Cell migration is essential for both organogenesis and tumor progression. Bone
      morphogenetic proteins (BMPs) are reported to be critical for not only bone
      formation but also tumor invasion. Here, we found that treatment with recombinant
      human BMP-2 (rhBMP-2) enhanced the haptotactic response of murine osteoblastic
      MC3T3-E1 and osteosarcoma Dunn cells to various extracellular matrix (ECM)
      components, including fibronectin, type I collagen, and laminin-1. Function
      blocking antibody against integrin alpha5beta1 partially inhibited haptotaxis to
      fibronectin, suggesting that the response was propagated via these integrins.
      rhBMP-2 slightly increased the expression level of integrin beta1, and enhanced
      the speed of cell spreading on fibronectin, focal adhesion formation and
      phosphorylation of focal adhesion kinase (FAK) at Tyr397. By means of sucrose
      gradient flotation, incorporation of integrin beta1 in fractions of detergent
      (CHAPS) resistant membrane was increased when the cells were treated with rhBMP
      2. Further, treatment with methyl-beta-cyclodextrin to deplete membrane
      cholesterol abrogated the effect of rhBMP-2 on haptotaxis, and exogenously added
      cholesterol reversed this inhibitory effect. Collectively, these results provide
      insights into the mechanism by which BMP signaling enhances cell migration by
      modulating fibronectin-integrin beta1 signaling via cholesterol enriched membrane
      microdomains, lipid rafts.

PMID- 17022973
TI  - Actin-based modeling of a transcriptionally competent nuclear substructure
      induced by transcription inhibition.
AB  - During transcription inactivation, the nuclear bodies in the mammalian cells
      often undergo reorganization. In particular, the interchromatin granule clusters,
      or IGCs, become colocalized with RNA polymerase II (RNAP II) upon treatment with
      transcription inhibitors. This colocalization has also been observed in untreated
      but transcriptionally inactive cells. We report here that the reorganized IGC
      domains are unique substructure consisting of outer shells made of SC35, ERK2,
      SF2/ASF, and actin. The apparently hollow holes of these domains contain clusters
      of RNAP II, mostly phosphorylated, and the splicing regulator SMN. This class of
      complexes are also the sites where prominent transcription activities are
      detected once the inhibitors are removed. Furthermore, actin polymerization is
      required for reorganization of the IGCs. In connection with this,
      immunoprecipitation and immunostaining experiments showed that nuclear actin is
      associated with IGCs and the reorganized IGC domains. The study thus provides
      further evidence for the existence of an actin-based nuclear skeleton structure
      in association with the dynamic reorganization processes in the nucleus. Overall,
      our data suggest that mammalian cells have adapted to utilize the reorganized,
      uniquely shaped IGC domains as the temporary storage sites of RNAP II
      transcription machineries in response to certain transient states of
      transcription inactivation.

PMID- 17022974
TI  - Analysis of cerebellar Purkinje cells using EAAT4 glutamate transporter promoter
      reporter in mice generated via bacterial artificial chromosome-mediated
      transgenesis.
AB  - The EAAT4 glutamate transporter helps regulate excitatory neurotransmission and
      prevents glutamate-mediated excitotoxicity in the cerebellum.
      Immunohistochemistry and in situ hybridization have previously defined a
      cerebellar cell population expressing this protein. These methods, however, are
      not well suited for evaluating the dynamic regulation of the transporter and its
      gene-especially in living tissues. To better study EAAT4 expression and
      regulation, we generated bacterial artificial chromosome (BAC) promoter eGFP
      reporter transgenic mice. Histological analysis of the transgenic mice revealed
      that the EAAT4 promoter is active predominantly in Purkinje cells, but can also
      be modestly detected in other neurons early postnatally. EAAT4 promoter activity
      was not present in non-neuronal cells. Cerebellar organotypic slice cultures
      prepared from BAC transgenic mice provided a unique reagent to study transporter
      and Purkinje cell expression and regulation in living tissue. The correlation of
      promoter activity to protein expression makes the EAAT4 BAC promoter reporter a
      valuable tool to study regulation of EAAT4 expression.

PMID- 17022975
TI  - Phosphorylation of Numb regulates its interaction with the clathrin-associated
      adaptor AP-2.
AB  - Numb is thought to participate in clathrin-dependent endocytosis by directly
      interacting with the clathrin-associated adaptor complex AP-2, although the
      underlying mechanisms are unknown. Numb is also known to be phosphorylated at
      Ser(264)in vitro and in vivo. Here, we found that Numb is phosphorylated in vitro
      by Ca(2+)/calmodulin-dependent protein kinase I on Ser(283). This phosphorylation
      was also observed in transfected COS-7 cells, indicating its physiological
      relevance. Pull-down experiments showed that the phosphorylation of Numb impaired
      its binding to the AP-2 complex and simultaneously recruited 14-3-3 proteins in
      vitro. Based on experiments using Numb mutants, both the initial phosphorylation
      of Ser(264) and the subsequent phosphorylation of Ser(283) are sufficient to
      abolish the binding of Numb to AP-2 and to promote the interaction with 14-3-3
      protein. These findings suggest a novel mechanism for the regulation of Numb
      mediated endocytosis, namely through direct phosphorylation.

PMID- 17022976
TI  - Characterization of novel imidazole derivative, JM-8686, a potent inhibitor of
      allene oxide synthase.
AB  - The inhibitory properties of a first synthetic jasmonic acid biosynthesis
      inhibitor, JM-8686, were investigated. Steady-state kinetic analysis indicates
      that the compound is a competitive inhibitor of allene oxide synthase (AOS) with
      a K(i) value of approximate 0.62+/-0.15 microM. Dialysis experiment indicates
      that AOS inactivation by JM-8686 is reversible. The optical difference
      spectroscopy analysis of JM-8686 and AOS interaction indicates that JM-8686
      induced type II binding spectra with a K(d) value of approximate 1.6+/-0.2
      microM, suggesting that JM-8686 binds to the prosthetic heme iron of AOS.
      Comparison of the inhibitory potency of the compound against HPL (CYP74B) from
      tomato revealed that JM-8686 was a highly selective inhibitor for AOS.

PMID- 17022977
TI  - Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor
      involved in the virus life cycle.
AB  - Influenza virus matrix protein 1 (M1) has been shown to play a crucial role in
      the virus replication, assembly and budding. We identified heat shock cognate
      protein 70 (Hsc70) as a M1 binding protein by immunoprecipitation and MALDI-TOF
      MS. The C terminal domain of M1 interacts with Hsc70. We found that Hsc70 does
      not correlate with the transport of M1 to the nucleus, however, it does inhibit
      the nuclear export of M1 and NP, thus resulting in the inhibition of viral
      production. This is the first demonstration that Hsc70 is directly associated
      with M1 and therefore is required for viral production.

PMID- 17022979
TI  - Compositional properties of human cDNA libraries: practical implications.
AB  - The strikingly wide and bimodal gene distribution exhibited by the human genome
      has prompted us to study the correlations between EST-counts (expression levels)
      and base composition of genes, especially since existing data are contradictory.
      Here we investigate how cDNA library preparation affects the GC distributions of
      ESTs and/or genes found in the library, and address consequences for expression
      studies. We observe that strongly anomalous GC distributions often indicate
      experimental biases or deficits during their preparation. We propose the use of
      compositional distributions of raw ESTs from a cDNA library, and/or of the genes
      they represent, as a simple and effective tool for quality control.

PMID- 17022978
TI  - PHI-1 interacts with the catalytic subunit of myosin light chain phosphatase to
      produce a Ca(2+) independent increase in MLC(20) phosphorylation and force in
      avian smooth muscle.
AB  - In avian smooth muscles, GTPgammaS produces a Rho kinase mediated increase in PHI
      1 phosphorylation and force, but whether this correlation is causal is unknown.
      We examined the effect of phosphorylated PHI-1 (P-PHI-1) on force and myosin
      light chain (MLC(20)) phosphorylation at a constant [Ca(2+)]. P-PHI-1, but not
      PHI-1, increased MLC(20) phosphorylation and force, and phosphorylation of PHI-1
      increased the interaction of PHI-1 with PP1c. Microcystin induced a dose
      dependent reduction in the binding of PHI-1 to PP1c. These results suggest PHI-1
      inhibits myosin light chain phosphatase by interacting with the active site of
      PP1c to produce a Ca(2+) independent increase in MLC(20) phosphorylation and
      force.

PMID- 17022980
TI  - Endothelin-1 inhibits adipogenesis: role of phosphorylation of Akt and ERK1/2.
AB  - In adipogenesis, growth factors play a crucial role. Using serum depleted
      condition, we studied the causal role of endothelin-1 (ET-1) and epidermal growth
      factor (EGF), separately or together, in adipocyte differentiation of 3T3-L1
      cells. ET-1 stimulation caused an anti-adipogenic response and this effect was
      potentiated upon treatment with EGF. Co-treatment with EGF and ET-1 blocked the
      expression of C/EBPalpha and PPARgamma, the adipogenic markers. The inhibition of
      adipogenesis was preceded by a biphasic (early and late) attenuation of Akt
      phosphorylation. We suggest that treatment with ET-1 and EGF together induce a
      more potent anti-adipogenic response, involving increased Erk1/2 phosphorylation
      and biphasic attenuation of Akt phosphorylation.

PMID- 17022981
TI  - High-resolution X-ray microtomography for three-dimensional visualization of
      human stem cell muscle homing.
AB  - In the perspective of clinical translation of stem cell research, it would be
      advantageous to develop new techniques to detect donor cells after
      transplantation to track their fate and thus better understand their role in
      regeneration of damaged and diseased tissues. In this study we use X-ray computed
      microtomography for three-dimensional visualization of stem cells that were
      labeled with magnetic nanoparticles and transplanted via intra-arterial infusion.
      We show that X-ray computed microtomography offers the possibility to detect with
      high definition and resolution human cells after transplantation, and opens new
      possibilities for both experimental stem cell research.

PMID- 17022982
TI  - Validation of a prediction model for the follicle-stimulating hormone response
      dose in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To validate a published model for the prediction of the individual FSH
      response dose for gonadotropin induction of ovulation in polycystic ovary
      syndrome (PCOS). DESIGN: Structured, complete, and carefully monitored patient
      based data collection to test the external validity of the prediction model.
      SETTING: Twenty-nine hospitals in The Netherlands. PATIENT(S): Eighty-five
      clomiphene citrate (CC)-resistant women with PCOS. INTERVENTION(S): Ovulation
      induction in a chronic low-dose step-up FSH regimen. MAIN OUTCOME MEASURE(S):
      Predicted individual FSH response dose, defined as follicle growth >10 mm in
      diameter on ultrasound. RESULT(S): The model, using the women's body mass index,
      CC response, initial serum FSH level, and initial serum insulin-to-glucose ratio
      was studied in the validation sample. Overall, the FSH response dose predicted by
      the model was higher than the observed response dose. The predictive performance
      of the model was poor, with an R(2) of 0.11, and the average prediction error was
      35 IU. CONCLUSION(S): The external validity of the model predicting the
      individual FSH response dose was inadequate in women with CC-resistant PCOS
      undergoing ovulation induction with recombinant FSH in a low-dose step-up
      regimen.

PMID- 17022984
TI  - Testosterone and its effects on courtship in golden-collared manakins (Manacus
      vitellinus): seasonal, sex, and age differences.
AB  - Male golden-collared manakins gather on leks and perform an acrobatic display to
      attract females. In temperate breeding species, testosterone (T) activation of
      courtship displays has been well studied. Few studies have examined T activation
      of displays in tropical species; even fewer have explored the activational role
      of T in elaborate courtship displays such as in the manakin. In some tropical
      species, including manakins, territorial aggression or song behavior are
      uncoupled from T. We have previously shown that T activates display behavior in
      manakin males when endogenous T levels are low in the non-courtship season. To
      understand how T functions in breeding birds, we examined T levels in a large
      group of manakins sampled during the courtship and non-courtship season. In
      addition, during the courtship season, we gave T implants to adult males,
      juvenile males, and females. We found that T levels were low during the non
      courtship season and comparatively higher on average during the courtship season.
      However, T levels were low in many adult males during the courtship season,
      especially when compared to temperate breeding species. Regardless of initial
      endogenous T levels during the courtship season, T implants did not increase the
      display frequency of adult males. T-treated females and juvenile males did
      display under similar conditions. Our data suggest that the effects of T on
      manakin display vary with season, sex, and age and that high T is not necessary
      for display.

PMID- 17022983
TI  - Pineal-dependent and -independent effects of photoperiod on immune function in
      Siberian hamsters (Phodopus sungorus).
AB  - Siberian hamsters (Phodopus sungorus) exhibit reproductive and immunological
      responses to photoperiod. Short (<10-h light/day) days induce gonadal atrophy,
      increase leukocyte concentrations, and attenuate thermoregulatory and behavioral
      responses to infection. Whereas hamster reproductive responses to photoperiod are
      dependent on pineal melatonin secretion, the role of the pineal in short-day
      induced changes in immune function is not fully understood. To examine this,
      adult hamsters were pinealectomized (PINx) or sham-PINx, and transferred to short
      days (9-h light/day; SD) or kept in their natal long-day (15-h light/day; LD)
      photoperiod. Intact and PINx hamsters housed in LD maintained large testes over
      the next 12 weeks; sham-PINx hamsters exhibited gonadal regression in SD, and
      PINx abolished this effect. Among pineal-intact hamsters, blood samples revealed
      increases in leukocyte, lymphocyte, CD62L+ lymphocyte, and T cell counts in SD
      relative to LD; PINx did not affect leukocyte numbers in LD hamsters, but
      abolished the SD increase in these measures. Hamsters were then treated with
      bacterial lipopolysaccharide (LPS), which induced thermoregulatory (fever),
      behavioral (anorexia, reductions in nest building), and somatic (weight loss)
      sickness responses in all groups. Among pineal-intact hamsters, febrile and
      behavioral responses to LPS were attenuated in SD relative to LD. PINx did not
      affect sickness responses to LPS in LD hamsters, but abolished the ameliorating
      effects of SD on behavioral responses to LPS. Surprisingly, PINx failed to
      abolish the effect of SD on fever. In common with the reproductive system, PINx
      induces the LD phenotype in most aspects of the immune system. The pineal gland
      is required for photoperiodic regulation of circulating leukocytes and neural
      immune interactions that mediate select aspects of sickness behaviors.

PMID- 17022985
TI  - The impact on mothers of bringing up a child with intellectual disabilities: a
      cross-cultural study.
AB  - BACKGROUND: Most research into the impact on mothers of having a child with an
      intellectual disability has been done in Western cultures. These mothers are at
      increased risk of stress, along with poorer health and weakened family
      relationships. Nurses are well placed to support these mothers. OBJECTIVES: (1)
      To describe across three different cultures-Irish, Taiwanese and Jordanian-the
      inter-relationships among three indicators of maternal well-being. (2) To
      identify the coping strategies of mothers and the professional and informal
      supports available to them. (3) To identify the variables that have a negative
      impact on maternal well-being and possible moderating influences on them. DESIGN:
      A survey approach with three groups of self-selected mothers. PARTICIPANTS: The
      characteristics of the child determined the inclusion criteria; namely aged 5-18
      years with a diagnosis of intellectual disability of such severity that the
      children attended special schools or centres. In each country, the special
      services within particular geographical areas were approached and all families
      known to them were given the opportunity to participate. In all 206 mothers
      agreed to participate. METHODS: Mothers were interviewed individually at home or
      in the day centre attended by their child. They completed various rating scales
      of known reliability and validity. In addition they described in their own words,
      the impact the child had on their lives and how they coped. RESULTS: In all three
      countries, mothers experienced poor mental health, increased levels of child
      related stress and poorer family functioning which the qualitative data further
      illuminated. Their child's behaviour problems were a major factor in this. The
      impacts on mothers' well-being were not alleviated by access to professional
      supports or use of coping strategies. CONCLUSIONS: Health professionals need to
      adopt family-centred approaches that embrace the support needs of mothers.
      Similar strategies would apply across all cultures although they must be
      responsive to individual need.

PMID- 17022986
TI  - L5, the most electronegative subfraction of plasma LDL, induces endothelial
      vascular cell adhesion molecule 1 and CXC chemokines, which mediate mononuclear
      leukocyte adhesion.
AB  - We have previously reported that L5, the most negatively charged subfraction of
      plasma low-density lipoprotein (LDL), induces mononuclear leukocyte (MNC)
      adhesion under flow conditions in vitro when endothelial cells are incubated with
      L5. The present study was undertaken to identify responsible adhesion molecules
      and chemokines. LDL isolated from patients with homozygous familial
      hypercholesterolemia was separated into five distinct subfractions by high
      capacity ion-exchange chromatography. Differentially expressed mRNA between human
      umbilical vein endothelial cells (HUVEC) incubated (for 22h) with the earliest
      subfraction (L1: 20 microg/ml) and the latest and most negatively charged
      subfraction (L5: 20 microg/ml) was identified by DNA microarray analysis using
      three independent sets of RNA. mRNA consistently upregulated by L5 included VCAM
      1 (2.3-fold) and CXC chemokines GRO-alpha (2.3), GRO-beta (4.6), IL-8 (2.5), ENA
      78 (2.3), GRO-gamma (1.6) and GCP-2 (1.5). These results were validated by
      Northern analysis, semi-quantitative RT-PCR or ELISA. Blocking studies using
      monoclonal antibodies revealed that both primary capture and stable adhesion of
      MNC to HUVEC and human aortic endothelial cells (HAEC) incubated with L5 was
      mediated by VCAM-l/alpha4 integrin, whereas GRO and its receptor CXCR2 were
      involved in the stable adhesion of MNC to L5-treated HAEC.

PMID- 17022987
TI  - Determination of phthalates in water samples using polyaniline-based solid-phase
      microextraction coupled with gas chromatography.
AB  - A simple solid-phase microextraction (SPME) device, coupled with gas
      chromatography-flame ionization detection (GC-FID), was developed to detect trace
      levels of phthalates in environmental water samples. Polyaniline (PANI) was
      chosen as the sorbent for the SPME device and was electrochemically deposited on
      a stainless steel wire to achieve high thermal and mechanical stability. The
      porous structure of the PANI film, characterized by scanning electron microscopy
      (SEM), suggested large extraction capability. Key parameters were optimized and
      five phthalates were selected to evaluate the SPME-GC procedures. The method was
      also applied to the analysis of lake and river water samples. Control experiments
      were carried out using commercial polyacrylate (PA) fiber. The new PANI-SPME-GC
      method offers high accuracy, precision and sensitivity and low detection limits.
      Thus, the method developed could be used as a new way to monitor the trace levels
      of phthalates in water medium. A possible extraction mechanism was investigated
      using electrochemical impedance spectroscopy (EIS).

PMID- 17022988
TI  - Characterization of discontinuous buffer junctions using pH indicators in
      capillary electrophoresis for protein preconcentration.
AB  - An effective sample preconcentration technique for proteins and peptides was
      recently developed using capillary electrophoresis (CE) with discontinuous
      buffers [C.A. Nesbitt, J.T.-M. Lo, K.K.-C. Yeung, J. Chromatogr. A 1073 (2005)
      175]. Two buffers of different pH created a junction to trap the sample molecules
      at their isoelectric points and resulted in over 1000-fold preconcentration for
      myoglobin within 30 min. To study the formation of pH junctions in CE, a pH
      indicator, bromothymol blue, is used in this work to reveal the pH changes at the
      discontinuous buffer boundary. Bromothymol blue (BTB) exhibits a drastic change
      in its visible absorption spectrum (300-600 nm) going from the acidic to basic pH
      conditions, and is therefore ideal for visualizing the changes in pH at the
      junctions created by various buffer combinations. Preconcentration of myoglobin
      was performed in discontinuous buffers containing BTB. Major differences in the
      BTB absorption profiles were identified from buffer systems that differ
      significantly in preconcentration performance, which in turn, allowed for the
      identification of ideal buffers for sample preconcentration. Up to 2000-fold
      preconcentrations of myoglobin were achieved in the buffer systems studied in
      this work. In addition, the role of the electroosmotic flow (EOF) on the
      preconcentration performance was investigated. A low EOF was found to be
      desirable, as the pH junction could stay longer in the capillary for accumulation
      of proteins. The pH junction also displayed characteristics to resist
      bandbroadening. Potential laminar flow resulted from the mismatched residual EOFs
      under the two pH conditions within the discontinuous buffers appeared to have
      minimal effect on the preconcentration. In fact, external applied pressure can be
      used to control the migration of the pH junction without compromising the protein
      preconcentration.

PMID- 17022989
TI  - Phase behavior and the partitioning of caveolin-1 scaffolding domain peptides in
      model lipid bilayers.
AB  - The membrane binding and model lipid raft interaction of synthetic peptides
      derived from the caveolin scaffolding domain (CSD) of the protein caveolin-1 have
      been investigated. CSD peptides bind preferentially to liquid-disordered domains
      in model lipid bilayers composed of cholesterol and an equimolar ratio of
      dioleoylphosphatidylcholine (DOPC) and brain sphingomyelin. Three caveolin-1
      peptides were studied: the scaffolding domain (residues 83-101), a water
      insoluble construct containing residues 89-101, and a water-soluble construct
      containing residues 89-101. Confocal and fluorescence microscopy investigation
      shows that the caveolin-1 peptides bind to the more fluid cholesterol-poor phase.
      The binding of the water-soluble peptide to lipid bilayers was measured using
      fluorescence correlation spectroscopy (FCS). We measured molar partition
      coefficients of 10(4) M(-1) between the soluble peptide and phase-separated lipid
      bilayers and 10(3) M(-1) between the soluble peptide and bilayers with a single
      liquid phase. Partial phase diagrams for our phase-separating lipid mixture with
      added caveolin-1 peptides were measured using fluorescence microscopy. The water
      soluble peptide did not change the phase morphology or the miscibility transition
      in giant unilamellar vesicles (GUVs); however, the water-insoluble and full
      length CSD peptides lowered the liquid-liquid melting temperature.

PMID- 17022991
TI  - Fabrication of CdSe composite by using the amphiphilic block copolymer as
      template.
AB  - CdSe nanoparticles of improved stability against aggregation were synthesized by
      using amphiphilic block copolymer polyacrylonitrile-block-poly(ethylene glycol)
      block-polyacrylonitrile (PAN-b-PEG-b-PAN, PEA). The products were characterized
      by X-ray diffraction (XRD), high-resolution transmission electron microscopic
      (HRTEM). The optical properties were characterized by UV-vis spectrophotometer
      and the room temperature photoluminescence (PL). The results revealed that the
      CdSe nanoparticles have been uniformly distributed throughout the copolymer with
      diameters of 6-7 nm and the produced novel hybrid nanocomposites displayed
      obviously quantum size effects and interesting fluorescence features. FTIR
      results provided the information on the interaction between the copolymer and the
      nanoparticles. The TGA revealed that the thermal property of the copolymer
      enhanced due to the interaction of the nanoparticles and the groups of the
      copolymer.

PMID- 17022990
TI  - Experimental investigation of nanoparticle dispersion by beads milling with
      centrifugal bead separation.
AB  - A new type of beads mill for dispersing nanoparticles into liquids has been
      developed. The bead mill utilizes centrifugation to separate beads from
      nanoparticle suspensions and allows for the use of small sized beads (i.e. 15-30
      microm in diameter). The performance of the beads mill in dispersing a suspension
      of titanium dioxide nanoparticle with 15 nm primary particles was evaluated
      experimentally. Dynamic light scattering was used to measure titania particle
      size distributions over time during the milling process, and bead sizes in the 15
      100 microm range were used. It was found that larger beads (50-100 microm) were
      not capable of fully dispersing nanoparticles, and particles reagglomerated after
      long milling times. Smaller beads (15-30 microm) were capable of dispersing
      nanoparticles, and a sharp peak around 15 nm in the titania size distribution was
      visible when smaller beads were used. Because nanoparticle collisions with
      smaller beads have lower impact energy, it was found by X-ray diffraction and
      transmission electron microscopy that changes in nanoparticle crystallinity and
      morphology are minimized when smaller beads are used. Furthermore, inductively
      coupled plasma spectroscopy was used to determine the level of bead contamination
      in the nanoparticle suspension during milling, and it was found that smaller
      beads are less likely to fragment and contaminate nanoparticle suspensions. The
      new type of beads mill is capable of effectively dispersing nanoparticle
      suspensions and will be extremely useful in future nanoparticle research.

PMID- 17022992
TI  - Conductometric evidence for intact polyion-induced liposome clusters.
AB  - In this note, we present a set of electrical conductivity measurements of polyion
      induced liposome aggregate aqueous suspensions that supports evidence for the
      existence of a cluster phase in low-density colloidal systems. Heavily NaCl
      loaded liposomes, dispersed in a low-conductivity aqueous solution, are forced by
      electrostatic interactions with oppositely charged polyions to build up into
      individual aggregates, where the single vesicles maintain their integrity and,
      upon an external force, are able to release their ionic content. The conductivity
      data, within the effective medium approximation theory for heterogeneous systems,
      are in agreement with the picture of a suspension built up by clusters of
      vesicles which are able to preserve their content from the external medium. This
      finding opens new possibilities in multicompartment drug delivery techniques.

PMID- 17022993
TI  - Decoration carbon nanotubes with Pd and Ru nanocrystals via an inorganic reaction
      route in supercritical carbon dioxide-methanol solution.
AB  - This work describes a method to decorate carbon nanotubes (CNTs) with metallic Pd
      and Ru nanocrystals via inorganic reactions in supercritical (SC) CO2-methanol
      solutions. In this route, PdCl2 or RuCl3.3H2O dissolved in SC CO2-methanol
      solution acted as a metal precursor and CNTs functioned as a template to direct
      the deposition of produced nanoparticles. Methanol served as the reductant for
      the precursors as well as cosolvent to enhance the dissolution of precursors in
      SC CO2. Dry products were readily obtained through in situ extraction with SC CO2
      after reactions. The products were characterized by X-ray diffraction, X-ray
      photoelectron spectroscopy, and transmission electron microscopy. It was
      demonstrated that the loading content and particle size of the nanoparticles
      deposited on CNTs could be tuned by changing the weight ratio of the precursor to
      CNTs. This simple and efficient approach may also be utilized to synthesize other
      high-purity materials using inorganic salt precursors in SC CO2-based solution.

PMID- 17022995
TI  - Filtration of deformable emulsion droplets.
AB  - Oil-in-water (o/w) emulsions of different droplet size were filtered on membranes
      of various pore sizes to investigate the growth and behaviour of o/w filter
      cakes. The cake desorptivity S and the filter membrane resistance R were measured
      at various filtration pressures P. The variation of S with P shows that filter
      cake oil droplets of radius a are effectively rigid for P << gamma/a and fully
      deformable for P >> gamma/a, where gamma is the oil-water interfacial tension.
      For the largest P, when S became P-independent, the filter cake remained water
      permeable as expected from theory.

PMID- 17022994
TI  - Influence of 4-cyano-4'-biphenylcarboxylic acid on the orientational ordering of
      cyanobiphenyl liquid crystals at chemically functionalized surfaces.
AB  - We report two methods that involve tailoring of the chemical composition of the
      nematic liquid crystal 4-cyano-4'-pentylbiphenyl to achieve control over the
      orientational ordering of the liquid crystal on chemically functionalized
      surfaces. The first method involves the direct addition of 4-cyano-4'
      biphenylcarboxylic acid to 4-cyano-4'-pentylbiphenyl. The second method involves
      exposure of 4-cyano-4'-pentylbiphenyl to ultraviolet light and photochemical
      generation of a range of products, including 4-cyano-4'-biphenylcarboxylic acid.
      The addition of the acid or exposure to ultraviolet light accelerated the rate at
      which the liquid crystal exhibited an orientational transition from planar to
      perpendicular (homeotropic) alignment on surfaces presenting ammonium groups. The
      appearance of the homeotropic orientation of the UV-treated 4-cyano-4'
      pentylbiphenyl on ammonium-terminated surfaces was dependent on the thickness of
      the film of liquid crystal (13-50 mum), consistent with a dipolar coupling
      between the liquid crystal and the electric field associated with an electrical
      double layer generated at the ammonium surface. Although the addition of 4-cyano
      4'-biphenylcarboxylic acid or UV treatment of the liquid crystal also promoted
      homeotropic orientations on surfaces presenting hydroxyl groups, the orientations
      of the UV-treated liquid crystal on the hydroxyl-terminated surface did not
      change with thickness of the film of liquid crystal in the manner observed on the
      ammonium-terminated surfaces. The latter result indicates that the mechanism
      leading to homeotropic anchoring on hydroxyl-terminated surfaces is distinct from
      that on ammonium-terminated surfaces. Measurements performed using polarization
      modulation infrared reflection-absorption spectroscopy suggest that hydrogen
      bonding between the 4-cyano-4'-biphenylcarboxylic acid and the hydroxyl
      terminated surface is responsible for the homeotropic anchoring on the surface.
      Finally, the orientation of the liquid crystal on methyl-terminated surfaces was
      not influenced by the addition of 4-cyano-4'-biphenylcarboxylic acid nor UV
      treatment. These results illustrate how the chemical composition of liquid
      crystals can be manipulated to achieve control over their ordering on surfaces
      that possess chemical functionality relevant to the development of liquid crystal
      based sensors and diagnostic tools. We illustrate the utility of this approach by
      using the tailored liquid crystal to amplify and optically transduce the presence
      of proteins arrayed on ammonium-terminated surfaces.

PMID- 17022996
TI  - Antigens for the selection of pan-variable number of tandem repeats motif
      specific human antibodies against Mucin-1.
AB  - Epitopes found on Mucin-1 are differentially expressed on tumour versus normal
      tissue. Such epitopes have also been shown to have a potential in immunotherapy
      and tumour detection. The major epitope explored in this context is located
      within the variable number of tandem repeats. It has however recently been
      demonstrated that this epitope exists in several sequence variants. The standard
      sequence is highly antigenic while the most common sequence variant is much less
      so. We have now explored routes employing defined synthetic antigens to ensure
      the development of human recombinant antibody specificities targeting both
      sequence variants of this epitope. These antibodies may serve as a platform for
      the development of human antibodies for efficient targeting of Mucin-1 in human
      disease.

PMID- 17022997
TI  - Interaction of the bacteria Xenorhabdus nematophila (Enterobactericeae) and
      Bacillus subtilis (Bacillaceae) with the hemocytes of larval Malacosoma disstria
      (Insecta: Lepidoptera: Lasiocampidae).
AB  - Malacosoma disstria larvae are a pest of deciduous trees. Little is known on the
      interaction of bacteria with the immediate hemocytic antimicrobial responses of
      these insects. Incubating dead Xenorhabdus nematophila and Bacillus subtilis with
      a mixture of serum-free granular cells and plasmatocytes in vitro revealed
      differential bacterial-hemocyte adhesion and differential discharge of lysozyme
      and phenoloxidase but not total protein. Although active phenoloxidase adhered
      equally to both bacterial species, X. nematophila limited enzyme activation
      whereas B. subtilis enhanced activation. Serum with active phenoloxidase (as
      opposed to tropolone-inhibited phenoloxidase) and purified insect lysozyme
      increased bacterial-hemocyte adhesion of both bacterial species. An apolipophorin
      III-like protein when incubated with hemocytes, limited their responses to glass
      slides and bacterial adhesion. However, initial binding of the protein to both
      bacteria increased granular cell levels with bacteria while lowering the
      plasmatocyte levels with adhering procaryotes. The protein also increased
      lysozyme and phenoloxidase activities. Although B. subtilis in vivo elicited a
      nodulation-based decline in total hemocyte counts and did not affect hemocyte
      viability, dead X. nematophila elevated hemocyte counts and damaged the hemocytes
      as lipopolysaccharide levels increased and X. nematophila emerged into the
      hemolymph. Apolipophorin-III-like protein once bound to the bacteria slowed their
      removal from the hemolymph.

PMID- 17022998
TI  - Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate
      interaction and transcriptional synergy with the pancreatic islet LIM HD
      transcription factor Isl1.
AB  - The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co
      expressed in pancreatic beta-cells and are required for the differentiation and
      function of these endocrine cells. HNF4alpha activates numerous genes and
      mutations in its gene are associated with maturity onset diabetes of the young.
      Cofactors and transcription factors that interact with HNF4alpha are crucial to
      modulate its transcriptional activity, since the latter is not regulated by
      conventional ligands. These transcriptional partners interact mainly through the
      HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2
      module. Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation
      of transcription of the HNF1alpha, PPARalpha and insulin I promoters. Isl1
      interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy
      terminal F domain for optimal interaction and transcriptional synergy. More
      specifically, we found that naturally occurring HNF4alpha isoforms, differing
      only in their F domain, exhibited different abilities to interact and synergize
      with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha
      F domain. HNF4alpha interacted with both the homeodomain and the first LIM domain
      of Isl1. We found that the transcriptional synergy between HNF4alpha and Isl1
      involved an increase in HNF4alpha loading on promoter. The effect was more
      pronounced on the rat insulin I promoter containing binding sites for both
      HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding
      site. Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2
      resulting in a further transcriptional enhancement of the HNF1alpha promoter
      activity.

PMID- 17022999
TI  - The beta4-beta8 groove is an ATP-interactive site in the alpha crystallin core
      domain of the small heat shock protein, human alphaB crystallin.
AB  - The site for ATP interactions in human alphaB crystallin, the archetype of small
      heat-shock proteins, was identified and characterized to resolve the
      controversial role of ATP in the function of small heat-shock proteins.
      Comparative sequence alignments identified the alphaB crystallin sequence,
      (82)KHFSPEELKVKVLGD(96) as a Walker-B ATP-binding motif that is found in several
      ATP-binding proteins, including five molecular chaperones. Fluorescence resonance
      energy transfer and mass spectrometry using a novel fluorescent ATP analog, 8
      azido-ATP-[gamma]-1-naphthalenesulfonic acid-5(2-aminoethylamide) (azido-ATP
      EDANS) and a cysteine mutant of human alphaB crystallin (S135C) conjugated with a
      fluorescent acceptor, eosin-5-maleimide (EMA) identified the beta4-beta8 groove
      as the ATP interactive site in alphaB crystallin. A 44% decrease in the emitted
      fluorescence of azido-ATP-EDANS at the absorption maximum of S135C-EMA and a
      corresponding 50% increase in the fluorescence emission of S135C-EMA indicated a
      close spatial relationship between azido-ATP-EDANS and the center of the beta8
      strand ((131)LTITSSLS(138)). Liquid chromatography, electrospray ionization mass
      spectrometry identified two peptide fragments of the alphaB crystallin Walker-B
      motif photo-affinity-labeled with azido-ATP-EDANS confirming the beta4-beta8
      groove as an ATP interactive site. The results presented here clearly establish
      the beta4-beta8 groove as the ATP interactive region in alphaB crystallin, and
      are in contrast to the existing paradigm that classifies small heat-shock
      proteins as ATP-independent chaperones.

PMID- 17023000
TI  - DBC2 is essential for transporting vesicular stomatitis virus glycoprotein.
AB  - DBC2 is a tumor suppressor gene linked to breast and lung cancers. Although DBC2
      belongs to the RHO GTPase family, it has a unique structure that contains a Broad
      Complex/Tramtrack/Bric a Brac (BTB) domain at the C terminus instead of a typical
      CAAX motif. A limited number of functional studies on DBC2 have indicated its
      participation in diverse cellular activities, such as ubiquitination, cell-cycle
      control, cytoskeleton organization and protein transport. In this study, the role
      of DBC2 in protein transport was analyzed using vesicular stomatitis virus
      glycoprotein (VSVG) fused with green fluorescent protein. We discovered that DBC2
      knockdown hinders the VSVG transport system in 293 cells. Previous studies have
      demonstrated that VSVG is transported via the microtubule motor complex. We
      demonstrate that DBC2 mobility depends also on an intact microtubule network. We
      conclude that DBC2 plays an essential role in microtubule-mediated VSVG transport
      from the endoplasmic reticulum to the Golgi apparatus.

PMID- 17023001
TI  - Hippocampal volume reduction and HPA-system activity in major depression.
AB  - Structural imaging studies investigating hippocampal volumes in patients
      suffering from major depression have yielded mixed results. Here, 24 unipolar
      depressed in-patients and 14 healthy controls carefully matched for age, gender,
      and years of education underwent quantitative magnetic resonance imaging (MRI).
      Saliva cortisol was measured at 0800 and 1600 h in patients during a one-week
      wash-out and the following 4 weeks. Hippocampal volumes were significantly
      reduced in the patient group even after adjusting for intracranial brain volume
      (ICV) and age. Across groups, age was significantly negatively correlated with
      uncorrected hippocampal volumes. In patients, severity of disease (baseline HAMD
      scores) and baseline cortisol levels were not related to hippocampal volumes.
      However, there was a negative association between duration of the index episode
      before hospitalization and hippocampal volumes. Additionally, hippocampal volumes
      were significantly negatively correlated with duration of illness. Finally, we
      observed a trend for higher hippocampal volumes in those patients who showed a
      subsequent decrease in cortisol levels under pharmacotherapy.

PMID- 17023002
TI  - Molecular pathogenesis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common life-threatening
      malignancies in the world. This cancer generally arises within the boundaries of
      well-defined causal factors, of which viral hepatitis infection, aflatoxin
      exposure, chronic alcohol abuse, and nonalcoholic steatohepatitis are the major
      risk factors. Despite the identification of these etiological agents,
      hepatocarcinogenesis remains poorly understood. The molecular mechanisms leading
      to the development of HCC appear extremely complex and only recently have begun
      to be elucidated. Currently, surgical resection or liver transplantation offer
      the best chance of cure for the patient with HCC; however, these therapies are
      hindered by inability of many of these patients to undergo liver resection, by
      tumor recurrence and by donor shortages. A lack of suitable therapeutic
      strategies has led to a greater focus on prevention of HCC using antiviral agents
      and vaccination. Overall, the current outlook for patients with HCC is bleak;
      however, a better understanding of the molecular and genetic basis of this cancer
      should lead to the development of more efficacious therapies.

PMID- 17023003
TI  - Up-regulated L-type high voltage-gated calcium channels cause increase in
      diazepam binding inhibitor induced by sustained morphine exposure in mouse
      cerebrocortical neurons.
AB  - Mechanisms of increase in diazepam binding inhibitor (DBI) mRNA expression in
      mouse cerebrocortical neurons after sustained morphine exposure were
      investigated. Increases in DBI and its mRNA expressions induced by sustained
      morphine (0.3 microM) exposure for 3 days were completely abolished by naloxone
      and nifedipine, but not by omega-agatoxin VIA and omega-conotoxin GIVA. Increase
      in [(3)H]diltiazem binding to the particulate fractions from the morphine-treated
      neurons was due to increased B(max) value with no changes in K(d) value. Western
      blot analysis on L-type high voltage-gated calcium channel (HVCC) subunits
      revealed the increased expressions of alpha1C, alpha1D, and alpha2/delta1
      subunits and decreased of beta4 subunit expression, whereas expression of N- and
      P/Q-type HVCC subunits was not changed. These results indicate that morphine
      induced increase in DBI mRNA expression is mediated via increased Ca(2+) entry
      through up-regulated L-type HVCCs.

PMID- 17023004
TI  - Genotoxic potential of medroxyprogesterone acetate in cultured human peripheral
      blood lymphocytes.
AB  - Medroxyprogesterone acetate was studied at three different concentrations (1, 5
      and 10 microM), for its genotoxic effects in human peripheral blood lymphocyte
      culture using chromosomal aberrations and sister chromatid exchanges as
      parameters. Duplicate peripheral blood cultures were treated with three different
      concentrations (1, 5 and 10 microM) of medroxyprogesterone acetate. The study was
      carried out both in the absence as well as in the presence of metabolic
      activation (S9 mix) with and without NADP. Medroxyprogesterone acetate was found
      genotoxic at 5 and 10 microM in the presence of S9 mix with NADP. To study the
      possible mechanism of the genotoxicity of medroxyprogesterone acetate, superoxide
      dismutase and catalase at different doses were used separately and in combination
      with 10 microM of medroxyprogesterone at different doses in the presence of S9
      mix with NADP. Superoxide dismutase treatment results in an increase of the
      genotoxic damage but catalase treatment reduce the genotoxic damage of
      medroxyprogesterone acetate. Catalase treatment in combination with superoxide
      dismutase also results in the further reduction of the genotoxic damage. The
      results of the present study reveal that medroxyprogesterone acetate is genotoxic
      only in the presence of metabolic activation (S9 mix) with NADP. Treatments with
      superoxide dismutase and catalase suggests the possible generation of reactive
      oxygen species by redox cycling of various forms of quinones, similar to
      estrogens, that are the results of aromatic hydroxylation by cytochrome P450s.

PMID- 17023005
TI  - AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in
      post-myocardial infarction remodeling.
AB  - There are two subtypes of angiotensin (Ang) II receptors, AT1R and AT2R. It is
      established that clinical use of specific AT1R blocker (ARB) improves the long
      term prognosis of heart failure. However, scientific basis for such effects of
      ARB is incompletely understood. The present study was designed to determine
      whether ARB inhibits the left ventricular (LV) remodeling that occurs early after
      myocardial infarction (MI) and whether the benefit of ARB is mediated by blockade
      of AT1R itself or by stimulation of AT2R resulting from AT1R blockade. MI was
      induced in AT2R-knockout mice and wild-type mice. Administration of valsartan, an
      ARB, or vehicle was started soon after the surgery and continued for two weeks.
      Infarction caused significant increase in end diastolic and end systolic LV
      dimensions, LV/body weight ratio, and myocyte cross-sectional area (MCSA) in both
      strains to a similar extent. Lung/body weight ratio, an index of pulmonary
      congestion, was also significantly increased in both strains, but the magnitude
      of increase was significantly larger in knockout mice. Valsartan significantly
      reduced LV dimensions, LV/body weight ratio, MCSA, and lung/body weight ratio in
      wild-type mice. In knockout mice, however, valsartan failed to inhibit the
      increases in LV dimensions and LV/body weight ratio. After the treatment,
      lung/body weight ratio in the mutant strain was significantly larger than that in
      the wild-type mice. Valsartan attenuates acute phase post-infarction remodeling
      and ameliorates heart failure, and a large part of its cardioprotective effect
      was mediated by AT2R.

PMID- 17023006
TI  - The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and
      fracture healing in rat tibias.
AB  - Local and systemic release of transforming growth factor beta 1 (TGF-beta1) is
      known to increase during the process of fracture healing and this cytokine
      stimulates bone healing. The majority of the non steroidal anti inflammatory
      drugs (NSAIDs) inhibit fracture healing. Granulocyte colony stimulating factor (G
      CSF) is a hematopoietic growth factor that stimulates bone marrow. In this study,
      the effects of the NSAID naproxen sodium, G-CSF, and both of them in combination
      on the TGF-beta1 serum level in rats with tibia fractures were measured and
      fracture healing was evaluated by histopathologic and radiologic examination. The
      TGF-beta1 serum levels obtained on day one (24 h after fracture but before
      administration of naproxen or G-CSF) were found to be similar in all of the five
      groups (p > 0.05). At the end of the first week, TGF-beta1 levels were
      significantly lower in naproxen-treated rats than those of the other groups
      excluding control (p = 0.002). Similar changes in TGF-beta1 levels were found at
      the end of the second and fourth weeks. TGF-beta1 levels were significantly
      higher in G-CSF-treated rats at the end of the first, second and fourth weeks (p
      < 0.05). Fracture healing scores measured with histopathological and radiological
      methods were higher in G-CSF-treated rats than in naproxen-treated ones. When
      both naproxen and G-CSF were given, the scores resumed to normal. The results
      point to the negative effect of naproxen sodium on fracture healing is due to its
      decreasing effect on the level of TGF-beta1, which may be a new possible
      mechanism. Moreover, this negative effect can be inhibited by the use of G-CSF.

PMID- 17023007
TI  - High fat and high fructose diet induced intracranial atherosclerosis and enhanced
      vasoconstrictor responses in non-human primate.
AB  - The present study examined the effect of high fat and high fructose (HFF) diet on
      the development of atherosclerosis and vascular contractile responses in the
      cerebral artery and thoracic aorta in non-human primates. Female cynomolgus
      monkeys (age: 3 to 4 years) were divided into normal control diet (N=5) and HFF
      diet groups (N=5). Twenty-eight weeks after feeding the HFF diet, total
      cholesterol and low-density lipoprotein-cholesterol in serum were significantly
      increased in the HFF diet group compared to the control group. The
      ultrastructural analyses of the basilar artery and aorta demonstrated the
      infiltration of lipid-laden foam cells and the appearance of lipid droplet-filled
      smooth muscle cells in the monkeys fed with the HFF diet. In terms of vascular
      reactivity, there was significantly greater vasoconstriction of the aorta and
      basilar artery in response to 5-hydroxytryptamine in the HFF diet group compared
      to the normal diet-fed group. In addition, KCl-induced vasoconstriction of the
      basilar arteries was also significantly enhanced in the HFF diet group compared
      to the normal diet-fed monkeys. In all, our present study has demonstrated that
      changes in the vascular responsiveness of the cerebral artery and its cellular
      architecture may manifest into cerebrovascular complications consistent with a
      pathological state normally observed with the onset and progression of
      atherosclerosis.

PMID- 17023008
TI  - Ipsilateral corticospinal projections do not predict congenital mirror movements:
      a case report.
AB  - Congenital mirror movements (CMMs) are involuntary, symmetric movements of one
      hand during the production of voluntary movements with the other. CMMs have been
      attributed to a range of physiological mechanisms, including excessive
      ipsilateral projections from each motor cortex to distal extremities. We examined
      this hypothesis with an individual showing pronounced CMMs. Mirror movements were
      characterized for a set of hand muscles during a simple contraction task.
      Transcranial magnetic stimulation (TMS) was then used to map the relative input
      to each muscle from both motor cortices. Contrary to our expectations, CMMs were
      most prominent for muscles with the strongest contralateral representation rather
      than in muscles that were activated by stimulation of either hemisphere. These
      findings support a bilateral control hypothesis whereby CMMs result from the
      recruitment of both motor cortices during intended unimanual movements.
      Consistent with this hypothesis, bilateral motor cortex activity was evident
      during intended unimanual movements in an fMRI study. To assess the level at
      which bilateral recruitment occurs, motor cortex excitability during imagined
      unimanual movements was assessed with TMS. Facilitory excitation was only
      observed in the contralateral motor cortex. Thus, the bilateral recruitment of
      the hemispheres for unilateral actions in individuals with CMMs appears to occur
      during movement execution rather than motor planning.

PMID- 17023009
TI  - Chronic restraint or variable stresses differently affect the behavior,
      corticosterone secretion and body weight in rats.
AB  - Organisms are constantly subjected to stressful stimuli that affect numerous
      physiological processes and activate the hypothalamo-pituitary-adrenal (HPA)
      axis, increasing the release of glucocorticoids. Exposure to chronic stress is
      known to alter basic mechanisms of the stress response. The purpose of the
      present study was to compare the effect of two different stress paradigms
      (chronic restraint or variable stress) on behavioral and corticosterone release
      to a subsequent exposure to stressors. Considering that the HPA axis might
      respond differently when it is challenged with a novel or a familiar stressor we
      investigated the changes in the corticosterone levels following the exposure to
      two stressors: restraint (familiar stress) or forced novelty (novel stress). The
      changes in the behavioral response were evaluated by measuring the locomotor
      response to a novel environment. In addition, we examined changes in body,
      adrenals, and thymus weights in response to the chronic paradigms. Our results
      showed that exposure to chronic variable stress increased basal plasma
      corticosterone levels and that both, chronic restraint and variable stresses,
      promote higher corticosterone levels in response to a novel environment, but not
      to a challenge restraint stress, as compared to the control (non-stressed) group.
      Exposure to chronic restraint leads to increased novelty-induced locomotor
      activity. Furthermore, only the exposure to variable stress reduced body weights.
      In conclusion, the present results provide additional evidence on how chronic
      stress affects the organism physiology and point to the importance of the chronic
      paradigm and challenge stress on the behavioral and hormonal adaptations induced
      by chronic stress.

PMID- 17023010
TI  - Acute effects of knowledge-based work on feeding behavior and energy intake.
AB  - The aim of this study was to evaluate the impact of knowledge-based work (KBW) on
      feeding behavior and spontaneous energy intake with the use of a repeated
      measures/within-subjects design. We used a two-session protocol including an ad
      libitum buffet preceded by either rest in a sitting position for 45 min or a
      cognitive task (reading a document and writing a summary of 350 words using a
      computer) over the same time period. In this regard, 15 healthy Laval University
      female students (mean age = 24.1+/-2.2 years, mean BMI = 24.0+/-4.3 kg/m2) were
      recruited to participate in this study. Anthropometric variables, energy
      expenditure, heart rate, blood pressure, food intake (dietary record), and
      appetite sensation markers were measured at each testing session, and two
      questionnaires [Three-Factor Eating Questionnaire (TFEQ) and State-Trait Anxiety
      Inventory (STAI)] were administered. In addition, a buffet-type meal was used to
      measure spontaneous energy intake and macronutrient preferences. We found that
      the mean energy expenditure of the two conditions was about comparable
      (difference of 13 kJ between the two tasks) whereas the mean ad libitum energy
      intake after the KBW task exceeded that measured after rest by 959 kJ (p < 0.01).
      Although a higher absolute energy intake was observed for the three
      macronutrients after the KBW task (p < 0.05), no specific preference was
      detected, as reflected by the comparable percent of energy from each
      macronutrient in the two conditions. No significant difference in appetite
      sensation markers was observed between the two conditions, although the subjects
      ate more in the buffet-type meal after the KBW task. Furthermore, the subjects
      did not compensate by decreasing food intake for the rest of the day, suggesting
      a net caloric surplus. We also observed negative correlations between cognitive
      dietary restraint (TFEQ) and spontaneous energy intake in both conditions. In
      conclusion, our results demonstrate that mental work solicited by KBW has the
      potential to induce a higher spontaneous energy intake. This also raises the
      possibility that KBW adds a new component to sedentariness that might further
      accentuate the positive energy balance that is more likely to occur when one is
      inactive.

PMID- 17023011
TI  - Consecutive pathological and immunological alterations during experimentally
      induced swine dysentery - a study performed by repeated endoscopy and biopsy
      samplings through an intestinal cannula.
AB  - The development of intestinal lesions after inoculation with Brachyspira
      hyodysenteriae was followed by repeated endoscopy and biopsy sampling through a
      caecal cannula. Seven eight-week-old pigs were cannulated and inoculated, two
      were cannulated but not inoculated, and two pigs were inoculated but not
      cannulated. Endoscopy, biopsy, and blood sampling to determine SAA (serum amyloid
      A), haptoglobin, cortisol, and WBC counts were performed at scheduled time
      points. At the third day of disease, endoscopy showed a hyperaemic, perturbed
      mucosa and excessive amount of mucus. Histologically, crypt hyperplasia,
      depletion of goblet cell mucus, and erosions were noted. Simultaneously, elevated
      acute phase proteins and circulating monocytes, and decreased number of
      intraepithelial CD3(+) cells were observed. After five days the pigs recovered.
      Intestinal lesions were demarcated and interspersed among apparently normal
      mucosa and blood parameters returned to initial values. Endoscopy through an
      intestinal cannula made it possible to follow the development of intestinal
      alterations in vivo and describe the sequential events during the course of swine
      dysentery. The number of animals used in a study could thus be minimised and the
      precision of the experiment increased.

PMID- 17023012
TI  - The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal:
      a common and potentially hazardous practice.
AB  - Many women of childbearing age from sub-Saharan Africa use topical skin
      lighteners, some of which present a risk of toxic systemic effects. The goals of
      this study were to evaluate, in this environment, the frequency of this practice
      during pregnancy, as well as eventual consequences on pregnancy. Ninety-nine
      women from 6 to 9 months pregnant were randomly selected among those attending a
      standard maternal centre in Dakar for a prenatal visit. Investigations consisted
      of questions about the use of skin lighteners, a standard clinical examination,
      follow-up until delivery and a morning blood sample for plasma cortisol levels.
      Sixty-eight of the 99 selected women used skin lighteners during their current
      pregnancy, the main active ingredients being hydroquinone and highly potent
      steroids (used by 64 and 28 women, respectively). No difference in the main
      outcomes of pregnancy were found between skin-lightener users and the others;
      however, women using highly potent steroids, when compared with those who did
      not, had a statistically significant lower plasma cortisol level and a smaller
      placenta, and presented a higher rate of low-birth-weight infants. Skin
      lightening is a common practice during pregnancy in Dakar, and the use of
      steroids may result in consequences in the mother and her child.

PMID- 17023014
TI  - Inhibition of iridovirus protein synthesis and virus replication by antisense
      morpholino oligonucleotides targeted to the major capsid protein, the 18 kDa
      immediate-early protein, and a viral homolog of RNA polymerase II.
AB  - Frog virus 3 (FV3) is a large DNA virus that encodes approximately 100 proteins.
      Although the general features of FV3 replication are known, the specific roles
      that most viral proteins play in the virus life cycle have not yet been
      elucidated. To address the question of viral gene function, antisense morpholino
      oligonucleotides (asMOs) were used to transiently knock-down expression of
      specific viral genes and thus infer their role in virus replication. We designed
      asMOs directed against the major capsid protein (MCP), an 18 kDa immediate-early
      protein (18K) that was thought to be a viral regulatory protein, and the viral
      homologue of the largest subunit of RNA polymerase II (vPol-IIalpha). All three
      asMOs successfully inhibited translation of the targeted protein, and two of the
      three asMOs resulted in marked phenotypic changes. Knock-down of the MCP resulted
      in a marked reduction in viral titer without a corresponding drop in the
      synthesis of other late viral proteins. Transmission electron microscopy (TEM)
      showed that in cells treated with the anti-MCP MO assembly sites were devoid of
      viral particles and contained numerous aberrant structures. In contrast,
      inhibition of 18K synthesis did not block virion formation, suggesting that the
      18K protein was not essential for replication of FV3 in fathead minnow (FHM)
      cells. Finally, consistent with the view that late viral gene expression is
      catalyzed by a virus-encoded or virus-modified Pol-II-like protein, knock-down of
      vPol-IIalpha triggered a global decline in late gene expression and virus yields
      without affecting the synthesis of early viral genes. Collectively, these results
      demonstrate the utility of using asMOs to elucidate the function of FV3 proteins.

PMID- 17023013
TI  - Complete genomic sequences, a key residue in the spike protein and deletions in
      nonstructural protein 3b of US strains of the virulent and attenuated
      coronaviruses, transmissible gastroenteritis virus and porcine respiratory
      coronavirus.
AB  - Transmissible gastroenteritis virus (TGEV) isolates that have been adapted to
      passage in cell culture maintain their infectivity in vitro but may lose their
      pathogenicity in vivo. To better understand the genomic mechanisms for viral
      attenuation, we sequenced the complete genomes of two virulent TGEV strains and
      their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller
      M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the
      ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally
      occurring TGEV deletion mutant with an altered respiratory tropism and reduced
      virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa)
      levels between virulent and attenuated TGEV strains identified a common change in
      nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa
      position 585 of the spike proteins of the attenuated TGEV strains. Alanine was
      also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine
      to alanine mutation resides in the region of the major antigenic site A/B (aa 506
      706) that elicits neutralizing antibodies and within the domain mediating the
      cell surface receptor aminopeptidase N binding (aa 522-744). Comparison of the
      predicted polypeptide products of ORF3b showed significant deletions in the
      naturally attenuated PRCV-ISU-1 and TGEV Miller M60; these deletions occurred at
      a common break point, suggesting a related mechanism of recombination that may
      affect viral virulence or tropism. Sequence comparisons at both genomic and
      protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV
      Miller strains than Purdue strains. Phylogenetic analyses showed that virulence
      is an evolutionarily labile trait in TGEV and that TGEV strains as a group share
      a common ancestor with PRCV.

PMID- 17023015
TI  - Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of
      T cell costimulatory molecules: direct effect of Vpr on T cell activation and
      immune function.
AB  - Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal
      host cellular immune pathways thus exploiting the cellular machinery for
      replication, survival and to escape host immune attack. Here we evaluated the
      direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr
      specifically downregulated the expression of CD28 and increased the expression of
      CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR
      was observed. Interferon gamma (IFN-gamma) production in T cells was evaluated as
      a measure of the downstream effector functions. Results indicate that Vpr
      significantly inhibited IFN-gamma production and this may, in part, due to Vpr's
      ability to inhibit the nuclear translocation of NF-kappaB, and its
      transcriptional regulation. Together these results support that HIV-1 Vpr
      selectively dysregulates the immune functions at multiple levels and exerts its
      inhibitory effects in the presence of other viral proteins.

PMID- 17023016
TI  - Structures required for poly(A) tail-independent translation overlap with, but
      are distinct from, cap-independent translation and RNA replication signals at the
      3' end of Tobacco necrosis virus RNA.
AB  - Tobacco necrosis necrovirus (TNV) RNA lacks both a 5' cap and a poly(A) tail but
      is translated efficiently, owing in part to a Barley yellow dwarf virus (BYDV)
      like cap-independent translation element (BTE) in its 3' untranslated region
      (UTR). Here, we identify sequence downstream of the BTE that is necessary for
      poly(A) tail-independent translation in vivo by using RNA encoding a luciferase
      reporter gene flanked by viral UTRs. Deletions and point mutations caused loss of
      translation that was restored by adding a poly(A) tail, and not by adding a 5'
      cap. The two 3'-proximal stem-loops in the viral genome contribute to poly(A)
      tail-independent translation, as well as RNA replication. For all necroviruses,
      we predict a conserved 3' UTR secondary structure that includes the BTE at one
      end of a long helical axis and the stem-loops required for poly(A) tail
      independent translation and RNA replication at the other end. This work shows
      that a viral genome can harbor distinct cap- and poly(A) tail-mimic sequences in
      the 3' UTR.

PMID- 17023018
TI  - Amino acid substitutions that specifically impair the transcriptional activity of
      papillomavirus E2 affect binding to the long isoform of Brd4.
AB  - The E2 protein of papillomaviruses binds to specific sites in the viral genome to
      regulate its transcription, replication and segregation in mitosis. Amino acid
      substitutions in the transactivation domain (TAD) of E2, of Arg37 and Ile73, have
      been shown previously to impair the transcriptional activity of the protein but
      not its ability to support viral DNA replication. To understand the biochemical
      basis of this defect, we have used the TADs of a low-risk (HPV11) and a high-risk
      (HPV31) human papillomavirus (HPV) as affinity ligands to capture proteins from
      whole cell extracts that can associate with these domains. The major TAD-binding
      protein was identified by mass spectrometry and western blotting as the long
      isoform of Brd4. Binding to Brd4 was also demonstrated for the E2 TADs of other
      papillomaviruses including cutaneous and animal types. For HPV11, HPV31 and CRPV
      E2, we found that binding to Brd4 is significantly reduced by substitutions of
      Arg37 and Ile73. Since these amino acids are located near each other in the 3
      dimensional structure of the TAD, we suggest that they define a conserved surface
      involved in binding Brd4 to regulate viral gene transcription.

PMID- 17023017
TI  - Sequence and annotation of the 314-kb MT325 and the 321-kb FR483 viruses that
      infect Chlorella Pbi.
AB  - Viruses MT325 and FR483, members of the family Phycodnaviridae, genus
      Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like
      green alga, Chlorella Pbi. The 314,335-bp genome of MT325 and the 321,240-bp
      genome of FR483 are the first viruses that infect Chlorella Pbi to have their
      genomes sequenced and annotated. Furthermore, these genomes are the two smallest
      chlorella virus genomes sequenced to date, MT325 has 331 putative protein
      encoding and 10 tRNA-encoding genes and FR483 has 335 putative protein-encoding
      and 9 tRNA-encoding genes. The protein-encoding genes are almost evenly
      distributed on both strands, and intergenic space is minimal. Approximately 40%
      of the viral gene products resemble entries in public databases, including some
      that are the first of their kind to be detected in a virus. For example, these
      unique gene products include an aquaglyceroporin in MT325, a potassium ion
      transporter protein and an alkyl sulfatase in FR483, and a dTDP-glucose
      pyrophosphorylase in both viruses. Comparison of MT325 and FR483 protein-encoding
      genes with the prototype chlorella virus PBCV-1 indicates that approximately 82%
      of the genes are present in all three viruses.

PMID- 17023019
TI  - Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein.
AB  - The cellular E3 ubiquitin ligase E6AP (UBE3A) interacts with the cancer
      associated HPV E6 oncoproteins, where together with the viral E6 oncoprotein it
      binds and targets the degradation of the p53 tumor suppressor. We find that the
      HPV-11E6 protein also associates with E6AP in vivo, and thereby can target the
      degradation of an E6-associated protein. Mutation of an E6-binding LXXLL peptide
      motif on E6AP eliminated the association, revealing a common mode of interaction
      between high- and low-risk E6 proteins and E6AP. E6AP was required for the in
      vivo degradation of DLG1 by both HVP-18 E6 and a chimeric HPV-11E6. The common
      functional interaction of both cancer-associated and non-cancer-associated E6
      proteins with E6AP establishes a common mechanism for E6 proteins trophic to
      mucosal squamous epithelium.

PMID- 17023020
TI  - Dissolved organic nitrogen removal during water treatment by aluminum sulfate and
      cationic polymer coagulation.
AB  - Coagulation of three surface waters was conducted with aluminum salt and/or
      cationic polymer to assess dissolved organic nitrogen (DON) removal. Coagulation
      with aluminum sulfate removed equal or slightly lower amounts of DON as compared
      to dissolved organic carbon (DOC). At aluminum sulfate dosages up to 5mg per mg
      DOC, the cationic polymer improved DON removal by an additional 15% to 20% over
      aluminum sulfate alone. At very high aluminum sulfate dosages (>8 mg aluminum
      sulfate per mg DOC), however, the cationic polymer addition negligibly increased
      DON removal. Molecular weight fractionation before and after coagulation
      experiments indicated that cationic polymer addition can increase the removal of
      all molecular weight fractions of DON with the highest molecular weight fraction
      (>10,000 Da) being preferentially removed. Results indicated that the DON added
      as part of the cationic polymer was almost completely removed at optimum aluminum
      sulfate and polymer doses.

PMID- 17023021
TI  - A method for determining pyrene in mucus using synchronous fluorimetry with
      multiple standard additions.
AB  - A new method was proposed to determine pyrene in mucus, which combined the
      synchronous fluorimetry with the multiple standard addition method (SFMSA). The
      method was used to determine pyrene in mucus directly without pretreatment. The
      method detection limit (MDL) for pyrene in mucus was measured as 0.47 ng/ml with
      a relative standard deviation of 12.7% (n = 7). The standard addition graph was
      linear in the range 0.05-50.00 ng/ml (r(2) = 0.9989). SFMSA was validated using a
      GC/MS method as a reference method, and nice agreement was found. The pyrene in
      mucus can be directly monitored by SFMSA without solvent extraction of samples.
      This indicates that SFMSA is more timesaving, less laborious and cheaper than the
      GC/MS method with solvent extraction. SFMSA has lower MDL and higher average
      recovery than the GC/MS method.

PMID- 17023022
TI  - Exposure to specific polychlorinated biphenyls and some chlorinated pesticides
      via breast milk in Poland.
AB  - The aim of our study was to obtain the data on the exposure of breast-fed infants
      to polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs)
      in the Wielkopolska province (Poland). The levels of indicator PCBs, and selected
      OCPs, including two DDT metabolites (HCB, p,p'-DDT, p,p'-DDD, p,p'-DDE and
      alpha,beta,gamma-HCH) were determined in 27 human milk samples, collected in 2000
      2001, according to WHO protocol. Estimated daily intakes (EDIs) of all analytes
      were calculated. Our results were compared with those obtained by an analysis of
      human milk samples from other European and non-European countries, collected in
      the same period time. We have stated that median exposure of Wielkopolska first
      breast-fed infants to OCPs is comparable (EDI(HCB) = 0.086 microg/kgbw/day;
      EDI(beta-HCH)=0.063 microg/kgbw/day) or higher (EDI(p,p'-DDE) = 3.495
      microg/kgbw/day) than in other European countries, while exposure to PCBs
      (EDI(Sigma7PCB) = 0.364 microg/kgbw/day) is situated at the low end of the intake
      of these xenobiotics by breast-fed infants from different regions of Europe.

PMID- 17023023
TI  - Monitoring of polychlorinated dibenzo-p-dioxins and dibenzofurans, dioxin-like
      PCBs and polycyclic aromatic hydrocarbons in food and feed samples from Ismailia
      city, Egypt.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
      polychlorinated biphenyl (PCBs) and polycyclic aromatic hydrocarbons (PAHs) have
      been determined using GC/HRMS in food (butter, seafood and meat) and feed samples
      (chicken, cattle and fish) purchased from Ismailia city, Egypt. PCDD/F
      concentrations in food samples ranged between 0.12 and 3.35 pg WHO TEQ/g wet w,
      while those in feed samples were between 0.08 and 0.2 pg WHO TEQ/g dry w. Levels
      of PCB TEQ ranged from 0.14 to 3.2 pg/g wet w in the food samples. The feed
      samples have an average of 0.35 pg PCB TEQ /g dry w. In this study, butter
      samples showed the highest contamination levels of PCDD/Fs and PCBs. The PCBs
      contribution to the total TEQ was on average 63% in seafood and on average 49%
      for meat and butter. The highest contamination levels of PCDD/Fs and PCBs were
      found in butter samples. The butter TEQ content is several times higher than that
      reported in all EU countries and exceeded the EU limits, while the PCDD/F levels
      in seafood and the feed samples is far below the current EU limit. Generally,
      congener profiles in the food samples reflect the non-industrialized nature of
      the city and suggest solid waste burning as a significant source of emission.
      Nevertheless, the profiles for butter suggest an impact from various sources. In
      the case of the sum of 16 PAH contamination levels in food samples were in the
      range of 11.7-154.3 ng/g wet w and feed samples had a range of 116-393 ng/g dry
      w. Benzo(a)pyrene (BaP) has been detected in the range of 0.05-3.29 ng/g wet w in
      the food samples; butter showed the highest contamination which exceeded the EU
      standard set for fats and oil. Fingerprints of PAHs suggested both petrogenic and
      pyrolytic sources of contamination.

PMID- 17023024
TI  - Changes in lead availability affect bacterial community structure but not basal
      respiration in a microcosm study with forest soils.
AB  - This study investigates the effects of Pb during time on the bacterial
      communities of forest soils using water-extractable Pb concentrations in the soil
      solution as predictors of Pb bioavailability. In a microcosm experiment we
      applied increasing concentrations of Pb(NO(3))(2) solutions (0.5, 2, 8, 32 mM) to
      5 forest soils of pH<5 and to a calcareous soil of pH>6.5. Sampling of the
      microcosms was performed after 3, 30 and 90 days of incubation. Community
      analysis included basal respiration rates and changes in the structure of the
      bacterial communities through T-RFLP fingerprinting. We also investigated
      functional stability in terms of resistance, expressed as the effects on basal
      respiration after 3 days of incubation, and of resilience, expressed as the
      recovery of bacterial community structure and of respiration rates after 90 days
      of incubation. Water-extractable Pb increased with time in most of the soils, in
      parallel with an increase of water-extractable dissolved organic carbon (DOC).
      The increased concentrations slightly affected bacterial community structure,
      although OTU (operational taxonomic unit) richness was not significantly reduced
      with Pb concentrations in any of the soils. The highest Pb treatment (32 mM)
      caused significant effects on basal respiration in some of the acidic soils, but
      no clear trend was observed in relation to increased Pb bioavailability with
      time. Resistance to Pb additions was evident in five of the six soils, but only
      two showed resilience after 90 days. This is the first study showing the effects
      of time on Pb bioavailability in soils and on the resulting reactions of the soil
      microbial communities.

PMID- 17023025
TI  - Dynamics of methane emissions from a freshwater marsh of northeast China.
AB  - In this paper, CH(4) flux was measured from Nov. 2002 to Oct. 2005, to estimate
      CH(4) emissions in winter and during freeze-thaw period, and interannual
      variation in CH(4) emissions in freshwater marsh in northeast China. The results
      showed that there was an obvious CH(4) emission (0.1-2.3 mg m(-2) h(-1)) in the
      freshwater marsh in winter. Flux of CH(4) in winter (November to March the next
      year) was about 3.8%, 5.5%, and 2.2% of the whole year in 2003, 2004, and 2005,
      respectively. Emission of CH(4) significantly increased during the freeze-thaw
      period (April-June), and was about 30.8%, 20.9%, and 20.6% of the whole year in
      2003, 2004, and 2005, respectively. Standing water depth greatly governed
      interannual variation of CH(4) emissions from marshes during the thaw-freeze
      period. Interannual variation of CH(4) emissions was significant during the
      growing season (p<0.05). Standing water depth during April to June was a primary
      factor, which affected the interannual variation of CH(4) flux during the growing
      season. Precipitation during the preceding non-growing season affected CH(4)
      emission indirectly via standing water depth.

PMID- 17023026
TI  - Bioaccessible arsenic in the home environment in southwest England.
AB  - Samples of household dust and garden soil were collected from twenty households
      in the vicinity of an ex-mining site in southwest England and from nine
      households in a control village. All samples were analysed by ICP-MS for pseudo
      total arsenic (As) concentrations and the results show clearly elevated levels,
      with maximum As concentrations of 486 microg g(-1) in housedusts and 471 microg
      g(-1) in garden soils (and mean concentrations of 149 microg g(-1) and 262 microg
      g(-1), respectively). Arsenic concentrations in all samples from the mining area
      exceeded the UK Soil Guideline Value (SGV) of 20 microg g(-1). No significant
      correlation was observed between garden soil and housedust As concentrations.
      Bioaccessible As concentrations were determined in a small subset of samples
      using the Physiologically Based Extraction Test (PBET). For the stomach phase of
      the PBET, bioaccessibility percentages of 10-20% were generally recorded. Higher
      percentages (generally 30-45%) were recorded in the intestine phases with a
      maximum value (for one of the housedusts) of 59%. Data from the mining area were
      used, together with default values for soil ingestion rates and infant body
      weights from the Contaminated Land Exposure Assessment (CLEA) model, to derive
      estimates of As intake for infants and small children (0-6 years old). Dose
      estimates of up to 3.53 microg kg(-1) bw day(-1) for housedusts and 2.43 microg
      kg(-1) bw day(-1) for garden soils were calculated, compared to the index dose
      used for the derivation of the SGV of 0.3 microg kg(-1) bw day(-1) (based on
      health risk assessments). The index dose was exceeded by 75% (18 out of 24) of
      the estimated As doses that were calculated for children aged 0-6 years, a group
      which is particularly at risk from exposure via soil and dust ingestion. The
      results of the present study support the concerns expressed by previous authors
      about the significant As contamination in southwest England and the potential
      implications for human health.

PMID- 17023028
TI  - Imposex in the golden apple snail Pomacea canaliculata in Taiwan.
AB  - The golden apple snail Pomacea canaliculata (Lamarck, 1822) was introduced into
      Taiwan intentionally in the early 1980s and has become a recurring pest that
      seriously threatens aquatic crops. In this study, a field description of imposex
      with a developed penis sheath and penis in female golden apple snails from
      crop/domestic wastewater drainage sites and a six-order river is presented for
      the first time. Based on the five field collections and the aquarium group, the
      vas deferens sequence (VDS) of P. canaliculata in imposex development was
      categorized into four stages, i.e., stage 0: without male genital system; stage
      1: with rudimentary penis; stage 2: with rudimentary penis and penis sheath; and
      stage 3: the rudimentary penis developing into penis pouch and penis. The VDS
      indices varied between 1.07 and 2.82 and were lowest in the aquarium group and
      Yuanlin2. Regarding the severity of imposex, the aquarium group was less
      pronounced, as illustrated by the length of penis sheath and penis length, than
      the field collections (p<0.05). In respect of the penis length, males of the most
      imposex-affected site were up to 15% shorter than that of the aquarium group.
      Negative correlations between male penis length and female imposex characters
      (i.e., penis length and penis sheath length) were also observed.

PMID- 17023027
TI  - Labile substrates quality as the main driving force of microbial mineralization
      activity in a poplar plantation soil under elevated CO2 and nitrogen
      fertilization.
AB  - Soil carbon (C) long term storage is influenced by the balance among ecosystem
      net primary productivity (NPP), the rate of delivery of new organic matter to
      soil pools and the decomposition of soil organic matter (SOM). The increase of
      NPP under elevated CO(2) can result in a greater production and higher turnover
      of fine roots or root exudation and, in turn, in an increase of labile C
      belowground. The aim of this work was to detect if changes in labile C substrates
      influenced the organic C storage in soils, verifying (i) whether treatments with
      elevated CO(2) and N fertilization induced changes in the amount and quality of
      labile C pools and in microbial C immobilization and (ii) whether these changes
      provoked modifications in the microbial C mineralization activity, and therefore
      changes in soil C losses. The effect of elevated CO(2) was a significant increase
      in both seasons (June and October 2004), of all labile C fractions: microbial
      biomass C (MBC), K(2)SO(4) extractable C (ExC), and water soluble C (WSC). The
      C/N ratio of the microbial biomass and of the K(2)SO(4) extractable SOM presented
      a seasonal fluctuation showing higher values in June, whereas the elevated CO(2)
      increased significantly the C/N ratio of these fractions independent of the
      season and the N addition, indicating a lower quality of labile SOM. Microbial
      respiration was more than doubled in October compared to June, confirming that
      changes in substrate quality and nutrient availability, occurring in the
      plantation at the beginning and at the end of the vegetative period, influenced
      the microbial activity in the bulk soil. Furthermore, the microbial respiration
      response to N fertilization was dependent on the season, with an opposite effect
      between June and October. The kinetic parameters calculated according to the
      first-order equation C(m)=C(0)(1-e(-kt)) were unaffected by elevated CO(2)
      treatment, except C(0)k and MR(basal), that showed a significant reduction,
      ascribable to (i) a lower quality of labile pools, and (ii) a more efficient
      microbial biomass in the use of available substrates. The C surplus found in
      elevated CO(2) soils was indeed immobilized and used for microbial growth, thus
      excluding a priming effect mechanism of elevated CO(2) on SOM decomposition.

PMID- 17023029
TI  - Self-monitoring versus standard monitoring of oral anticoagulation.

PMID- 17023030
TI  - An alternative pathway for fibrinolysis is activated in patients who have
      undergone cardiopulmonary bypass surgery and major abdominal surgery.
AB  - INTRODUCTION: We conducted this prospective study in order to investigate the
      hypotheses that an alternative pathway for fibrinolysis is activated in patients
      who have undergone cardiopulmonary bypass (CPB) surgery and major abdominal
      surgery and that the levels of fibrin degradation products digested by
      polymorphonuclear neutrophil elastase (elastase-XDP) and the D-dimer increase in
      the patients' plasma. MATERIALS AND METHODS: We studied a total of 77 patients
      who were scheduled to undergo either CPB surgery (36 patients) or major abdominal
      surgery (41 patients) and then measured the elastase-XDP and D-dimer levels at
      several time points both during and after the surgeries. The CPB surgery was
      divided into surgery for aortic dissection (AD) and cardiac surgery. The major
      abdominal surgery consists of hepatic resection and esophagectomy. RESULTS: The
      elastase-XDP and D-dimer levels significantly increased in the patients who
      underwent both CPB surgery and major abdominal surgery. The elastase-XDP levels
      in AD surgery showed highest values at the end of the CPB, while the levels in
      the other surgeries reached their peak on the day after the surgery. Statistical
      difference was seen in the levels of elastase-XDP among the three subgroups
      undergoing a hepatic resection. While we found significant correlations between
      the levels of elastase-XDP and D-dimer in patients undergoing CPB surgery and a
      subsegmentectomy of a cirrhotic liver, the correlation coefficients were markedly
      low in comparison to those of the other surgeries. CONCLUSIONS: Our findings
      demonstrated that the elastase-mediated pathway of fibrinolysis is activated to
      varying degrees depending on the surgery performed. Variations in the correlation
      coefficients between the levels of elastase-XDP and D-dimer may suggest that
      elastase-mediated fibrinolysis play a different role from the physiological
      fibrinolysis mediated by plasmin.

PMID- 17023031
TI  - Mesonephric adenocarcinoma of the cervix: a case report and review of the
      literature.
AB  - BACKGROUND: Malignant mesonephric tumor arising in the uterine cervix is an
      exceedingly uncommon variant of cervical adenocarcinoma with only 30 well
      documented cases in the literature. CASE: We present a case of a 54-year-old
      woman with postmenopausal vaginal bleeding who was found to have a stage IB
      mesonephric adenocarcinoma of the cervix. CONCLUSION: At present there is no
      consensus on a standardized treatment protocol for malignant mesonephric tumors
      of the cervix. The present case suggests that a favorable outcome may be achieved
      for patients with stage IB tumors with aggressive initial therapy.

PMID- 17023032
TI  - A high nuclear basal level of ERK2 phosphorylation contributes to the resistance
      of cisplatin-resistant human ovarian cancer cells.
AB  - OBJECTIVE: The aim of this study was to elucidate the role of ERK1/2 on cisplatin
      resistance in human ovarian cancer cells. METHODS: The relationship between
      nuclear levels of ERK2 and cisplatin-induced apoptosis in human ovarian carcinoma
      cell line, OVCAR-3, and in cells of the cisplatin-resistant subclone, OVCAR
      3/CDDP, was examined using immunoblotting and immunocytochemistry. RESULTS:
      Cisplatin treatment resulted in the activation of ERK2, both in OVCAR-3 and OVCAR
      3/CDDP cells. However, considerable levels of activated ERK2 existed in the
      nuclei of OVCAR-3/CDDP cells during serum starvation and in the early period (1-3
      h) after cisplatin treatment. Conversely, phospho-ERK2 was marginally detected in
      the nuclei of OVCAR-3 cells prior to cisplatin treatment. These phenomena were
      confirmed by immunofluorescence staining of the phosphorylated ERK2 in the nuclei
      of both cells. High basal phospho-ERK2 in the nuclei of OVCAR-3/CDDP cells
      contributed to cisplatin resistance, and was supported by several observations;
      (1) treatment of U0126, an inhibitor of MEK/ERK signaling pathway, partially
      sensitized OVCAR-3/CDDP cells to cisplatin; (2) pretreatment of OVCAR-3 cells
      with phorbol 12-myristate 13-acetate (PMA), an activator of ERK, induced nuclear
      translocation of activated ERK2, which led to the suppression of cisplatin
      induced apoptosis. CONCLUSIONS: These results collectively indicate that
      prelocalization of activated ERK2 in the nuclei contribute to cisplatin
      resistance in OVCAR-3/CDDP cells.

PMID- 17023033
TI  - Is time to chemotherapy a determinant of prognosis in advanced-stage ovarian
      cancer?
AB  - OBJECTIVES: Clinicians often question when to start chemotherapy after patients
      undergo surgery for ovarian cancer. A major unproven concern is whether a long
      postoperative delay reduces the benefits of an extensive procedure and leads to
      disease progression. Our objectives were to evaluate the correlation between
      clinical and pathologic variables and to evaluate the effect of the "time to
      chemotherapy" (TTC) interval on survival. METHODS: We retrospectively studied
      data from 218 patients with International Federation of Gynecology and Obstetrics
      stage IIIC or IV ovarian cancer (TNM stage T3c or T4) who were consecutively
      treated between January 1, 1994, and December 31, 1998. RESULTS: Mean age at
      diagnosis was 64 years (range, 24-87 years; median, 65 years), and 206 patients
      received postoperative platinum-based chemotherapy. Mean TTC interval was 26 days
      (range, 7-79 days; median, 25 days). No correlation was found between operative
      time and TTC interval length (P=0.99). Age and performance of rectosigmoidectomy
      were correlated with longer TTC interval (P=0.009 and P=0.005, respectively), but
      TTC was not a predictor of overall survival (odds ratio, 1.00; 95% confidence
      interval, 0.98-1.01; P=0.85). Differences in TTC interval length (< or =17 days,
      18-26 days, 27-33 days, or > or =34 days) did not affect survival (P=0.93). Even
      after categorizing patients by residual disease (<1 cm or > or =1 cm), no
      statistically significant effect of TTC on prognosis was identified. CONCLUSIONS:
      Concerns about the TTC interval should not be used to justify spending less time
      in the operative arena or using a more conservative approach for patients with
      advanced ovarian cancer.

PMID- 17023034
TI  - Preoperative serum YKL-40 is a marker for detection and prognosis of endometrial
      cancer.
AB  - OBJECTIVE: YKL-40 is a secreted glycoprotein of the chitinase family that has
      been previously described as a diagnostic and prognostic marker for a number of
      cancers, including epithelial ovarian cancer. In this study, we examined the
      frequency of serum elevation as well as the diagnostic and prognostic
      significance of this serum marker in endometrial cancer. MATERIALS AND METHODS:
      Preoperative serum levels of YKL-40 and CA125 were evaluated by enzyme-linked
      immunosorbent assay (ELISA) for all endometrial cancer patient samples (34)
      available in the Memorial Sloan-Kettering Cancer Center Gynecology Service Tissue
      Bank between the years 1987 and 2002, and compared to a cohort of normal
      individuals. A YKL-40 value of 61 ng/mL has previously been determined to
      represent the upper limit of normal. YKL-40 values were correlated with clinical
      characteristics, including patient age, tumor grade, histology, clinical stage,
      and clinical outcome (progression-free survival [PFS] and overall survival [OS]).
      RESULTS: YKL-40 was elevated (>61 ng/mL) in 26 (76%) of 34 endometrial cancer
      patients compared with elevations of CA125 in 21 (62%) of 34 patients (P=0.09).
      Twenty-eight (82%) of all 34 patients had elevations of either CA125 or YKL-40 or
      both; 16 (89%) of 18 advanced-stage endometrial cancer patients had elevation of
      at least one of these two markers. Median preoperative YKL-40 value was 137 ng/mL
      (range, 22-1738 ng/mL) for endometrial cancer patients compared with 28 ng/mL
      (range, 15-72 ng/mL) for normal healthy subjects (P<0.0001). There was no
      statistically significant association of YKL-40 with patient age, tumor grade,
      histology, or stage. Elevation of YKL-40 (>80 ng/mL) was correlated with poor
      clinical outcome in univariate analysis, but was not demonstrated in multivariate
      analysis. At 5 years' follow-up, the PFS rate was 80% for patients with YKL-40<80
      ng/mL compared with 43% for patients with YKL-40>80 ng/mL (P=0.004). The 5-year
      OS rate for patients with YKL-40<80 ng/mL was 79% compared with 48% for patients
      with YKL-40>80 ng/mL (P=0.047). CONCLUSION: Preoperative serum YKL-40 is
      frequently elevated and may represent a novel marker for the detection of
      endometrial cancer and the identification of high-risk subsets of patients with
      worse clinical outcome. Further investigation of this promising endometrial
      cancer marker in larger studies is warranted.

PMID- 17023036
TI  - Common polymorphism in interleukin 6 influences survival of women with ovarian
      and peritoneal carcinoma.
AB  - OBJECTIVES: The IL6 -174 promoter polymorphism impacts serum cytokine levels
      through transcriptional regulation. The objective of our study was to determine
      if -174 IL6 genotype influences survival in ovarian cancer. METHODS: The IL6 -174
      polymorphism was assessed by direct DNA sequencing in lymphocyte DNA from 160
      women with invasive ovarian, or peritoneal cancers. IL6 levels were measured in
      ascites and plasma in a subset of cases using colorimetric sandwich ELISA
      procedure. Overall survival was calculated according to the method of Kaplan and
      Meier. Cox regression analysis was used to evaluate the significance of
      individual variables in multivariate analysis. Chi-square or Fishers Exact was
      used to assess the significance of contingency tables. RESULTS: The IL6 -174
      genotype frequencies of CC (19%), CG (50%), and GG (31%) were in Hardy-Weinberg
      equilibrium and were similar to published frequencies in Caucasian controls.
      There were no associations with IL6 -174 genotype and age, stage or optimal
      cytoreduction. Stage had a significant impact on survival (p=0.003). The IL6 -174
      GG genotype was significantly associated with longer overall survival (median 131
      months) compared to CC or CG (median 28 months, p=0.0007). In cox regression
      analysis using the covariates genotype (p=0.006) and stage (p=0.02), both were
      independently significant. Furthermore, there was no association found between
      IL6 levels in ascites or plasma, and genotype, stage, or overall survival.
      CONCLUSIONS: The IL6 -174 GG genotype has a strong, independent, and favorable
      impact on survival for women with ovarian, and peritoneal carcinoma.

PMID- 17023037
TI  - Nicotine and smoker status moderate brain electric and mood activation induced by
      ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist.
AB  - As the increased smoking prevalence in schizophrenics may be interpreted as an
      adaptive response to an underlying biological defect, investigations into
      nicotine's actions within N-methyl-d-aspartate (NMDA) antagonist drug models of
      schizophrenia may improve our understanding of the role of glutamatergic
      neurotransmission in initiating and maintaining nicotine dependence in this
      disorder. In this double-blind, placebo-controlled, randomized study, the
      electroencephalographic (EEG) and subjective response to a sub-psychotomimetic
      intravenous dose of the NMDA antagonist ketamine was examined in 20 regular
      smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although
      nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain
      activation (decreased slow wave power) and sedation (decreased fast wave power
      and frequency), which were not affected by nicotine pretreatment and were evident
      only in non-smokers. Ketamine increased a number of self-report indices of
      subjective arousal, some of which were attenuated and potentiated by nicotine in
      smokers and non-smokers, respectively. These findings suggest that long-term
      (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine
      exposure may alter NMDA receptor-mediated arousal and mood systems in a way that
      promotes nicotine dependence in smokers, and addresses neurobiological
      deficiencies in smokers with schizophrenia.

PMID- 17023038
TI  - Sulfated steroids as endogenous neuromodulators.
AB  - Central nervous system function is critically dependent upon an exquisitely tuned
      balance between excitatory synaptic transmission, mediated primarily by
      glutamate, and inhibitory synaptic transmission, mediated primarily by GABA.
      Modulation of either excitation or inhibition would be expected to result in
      altered functionality of finely tuned synaptic pathways and global neural
      systems, leading to altered nervous system function. Administration of positive
      or negative modulators of ligand-gated ion channels has been used extensively and
      successfully in CNS therapeutics, particularly for the induction of sedation and
      treatment of anxiety, seizures, insomnia, and pain. Excessive activation of
      excitatory glutamate receptors, such as in cerebral ischemia, can result in
      neuronal damage via excitotoxic mechanisms. The discovery that neuroactive
      steroids exert rapid, direct effects upon the function of both excitatory and
      inhibitory neurotransmitter receptors has raised the possibility that endogenous
      neurosteroids may play a regulatory role in synaptic transmission by modulating
      the balance between excitatory and inhibitory neurotransmission. The sites to
      which neuroactive steroids bind may also serve as targets for the discovery of
      therapeutic neuromodulators.

PMID- 17023039
TI  - Smoking among adults with coronary heart disease.

PMID- 17023040
TI  - Artificial insemination in black-handed spider monkey (Ateles geoffroyi).
AB  - Artificial insemination (AI) was performed in spider monkeys; these primates are
      vulnerable to extinction and usually do not reproduce spontaneously in captivity.
      Uterine cycles were followed by daily assessment of vaginal cytology, and
      corroborated a posteriori by concentrations of 17-beta estradiol and
      progesterone, measured by radioimmunoassay (RIA), in fecal samples collected once
      daily. Five females between 13 to 27 years old were inseminated intravaginally
      (with fresh semen) twice each during the periovulatory phase (Days 9-12 of the
      menstrual cycle; Day 0, first day of menstrual bleeding), from September to the
      first 3 weeks of November (most fertile months). Transcervical AI was not useful
      in this primate because the liquid portion of the semen completely solidified
      instead of liquefying as in other primates. Pregnancies were apparently achieved
      in 5 of 14 attempts. One female became pregnant after the first round of
      inseminations, delivered a healthy infant, was inseminated and got pregnant again
      (subsequently aborted). One female aborted, apparently due to an intramural
      uterine leiomyoma. Another two females stopped menstruating for a few months,
      then restarted menstruating (these females may have been pregnant and aborted).
      In conclusion, in spider monkeys: (1) captivity-induced stress did not inhibit
      reproduction; (2) fecal steroid hormones were useful to assess cyclicity; (3) the
      semen coagulum, which apparently is a tightly packed and large reservoir of
      spermatozoa, must not be discarded but used in AI; (4) old female spider monkeys
      did not have cessation of reproductive function.

PMID- 17023041
TI  - Hydrodynamic properties of DNA and DNA-lipid complex in an elongational flow
      field.
AB  - The aim of this study was to determine the difference between hydrodynamic
      properties of DNA-cetyltrimethylammonium (CTA) complex and those of DNA, which
      may be related to the difference in fibre-forming ability of DNA-CTA from that of
      DNA. Responses of DNA and DNA-CTA complex to an elongational flow field were
      investigated. In both solution systems, results suggesting a coil-stretch
      transition were obtained. From a critical strain rate value, the radius of
      gyration of DNA-CTA molecules in ethanol-glycerol solution was revealed to be 0.3
      0.5 times of that of DNA in aqueous NaCl solution. Shear viscosity of DNA-CTA
      solution was much smaller than that of DNA solution, also suggesting a smaller
      size of DNA-CTA in ethanol-glycerol solution than that of DNA in aqueous NaCl
      solution. The plateau birefringence value of the DNA-CTA system, a parameter that
      indicates the local molecular conformation and the molecular arrangement, was
      only about 1/10 of that of the DNA system. There is an empirically determined
      molecular model of DNA-CTA complex in which a DNA molecule is sheathed by a
      cylindrical crust made of CTA chains. This structure reduces the DNA molecular
      density in a pure elongational flow field region but cannot explain the observed
      reduction of birefringence intensity. The small plateau birefringence value of
      DNA-CTA compared with that of DNA was attributed to the reduced molecular
      polarizability by the particular conformation of DNA molecules and CTA chains in
      the DNA-CTA system such as that expected by the conformational models.

PMID- 17023042
TI  - Surface-textured PEG-based hydrogels with adjustable elasticity: Synthesis and
      characterization.
AB  - Poly(ethylene glycol)-dimethacrylate (PEGDMA)-based hydrogels with adjustable
      shear modulus within the range of 10kPa to 1MPa and precisely predefinable
      surface textures on a micro-scale were made. It was observed that the volume of
      all hydrogels after preparation almost exactly matched the volume of the
      precursor solution and that there were only slight volume changes upon
      equilibration in excess solvent. This characteristic swelling behavior enables
      the preparation of textures on the hydrogel's surface with precisely predefinable
      dimensions. The behavior can be modeled with the Flory-Huggins theory assuming a
      concentration-dependent polymer-solvent interaction parameter. Additionally,
      activation of the hydrogels by electrophilic oxirane groups creates reactive
      sites that will enable the later grafting of the hydrogel's surface with various
      specific nucleophiles, e.g. biomolecules. Thus, these hydrogels are particularly
      suitable as biomaterials for systematic investigations of cellular response to
      surface topography and elasticity of the substrate, both in vivo and in vitro.

PMID- 17023044
TI  - Calcium gradients and the Golgi.
AB  - Changes in intracellular free calcium regulate many intracellular processes. With
      respect to the secretory pathway and the Golgi apparatus, changes in calcium
      concentration occurring either in the adjacent cytosol or within the lumen of the
      Golgi act to regulate Golgi function. Conversely, the Golgi sequesters calcium to
      shape cytosolic calcium signals as well as initiate them by releasing calcium via
      inositol-1,4,5-triphosphate (IP(3)) receptors, located on Golgi membranes. Local
      calcium transients juxtaposed to the Golgi (arising from release by the Golgi or
      other organelles) can activate calcium dependent signalling molecules located on
      or around the Golgi. This review focuses on the reciprocal relationship between
      the cell biology of the Golgi apparatus and intracellular calcium homeostasis.

PMID- 17023043
TI  - The Mu class glutathione transferase is abundant in striated muscle and is an
      isoform-specific regulator of ryanodine receptor calcium channels.
AB  - Members of the glutathione transferase (GST) structural family are novel
      regulators of cardiac ryanodine receptor (RyR) calcium channels. We present the
      first detailed report of the effect of endogenous muscle GST on skeletal and
      cardiac RyRs. An Mu class glutathione transferase is specifically expressed in
      human muscle. An hGSTM2-2-like protein was isolated from rabbit skeletal muscle
      and sheep heart, at concentrations of approximately 17-93 microM. When added to
      the cytoplasmic side of RyRs, hGSTM2-2 and GST isolated from skeletal or cardiac
      muscle, modified channel activity in an RyR isoform-specific manner. High
      activity skeletal RyR1 channels were inactivated at positive potentials or
      activated at negative potentials by hGSTM2-2 (8-30 microM). Inactivation became
      faster as the positive voltage was increased. Channels recovered from
      inactivation when the voltage was reversed, but recovery times were significantly
      slowed in the presence of hGSTM2-2 and muscle GSTs. Low activity RyR1 channels
      were activated at both potentials. In contrast, hGSTM2-2 and GSTs isolated from
      muscle (1-30 microM) in the cytoplasmic solution, caused a voltage-independent
      inhibition of cardiac RyR2 channels. The results suggest that the major GST
      isoform expressed in muscle regulates Ca2+ signalling in skeletal and cardiac
      muscle and conserves Ca2+ stores in the sarcoplasmic reticulum.

PMID- 17023045
TI  - Regulation of RUNX1/AML1 during the G2/M transition.
AB  - The acute myeloid leukemia 1 (AML1, RUNX1) transcription factor is a key
      regulator of hematopoietic differentiation both in embryonic stem cells and
      mature hematopoietic progenitors. The RUNX1 protein is thought to play a role in
      the control of progression through the cell cycle. We have shown that post
      transcriptional regulation of RUNX1 activity occurs, in part, through
      phosphorylation. To investigate whether transit through the cell cycle is
      associated with changes in the phosphorylation of RUNX1, we have derived phospho
      specific antibodies against three of the five major phosphorylation sites in the
      transcriptional activation domain of RUNX1, S276, S303 and S462. Using these
      antibodies we demonstrate that treatment of Jurkat T-cells with nocodazole, a
      G2/M blocking compound, causes an increase in phosphorylation of these three
      amino acids. By elutriating the Jurkat cells, we are able to demonstrate that
      these amino acids are normally phosphorylated at the G2/M phase of the cell
      cycle. Using in vivo inhibitors and in vitro assays this phosphorylation appears
      to be dependent on Cdk1. We find that RUNX1 degradation occurs at the G2/M-G1
      transition and is regulated by both Cdc20 and phosphoryation, suggesting that the
      anaphase promoting complex plays a role in modifying the level of this protein.
      Regulation of the extent of phosphorylation of RUNX1 may play a role in
      controlling the degradation of the protein, implying that additional E3 ligases
      may also be involved.

PMID- 17023046
TI  - Influence of genetic polymorphisms on the risk of developing leukemia and on
      disease progression.
AB  - BACKGROUND: Recent studies have provided evidence that common genetic variations
      with low penetrance could account for a proportion of leukemia and could also
      influence disease outcome, although the results obtained are still controversial.
      MATERIAL AND METHODS: We reviewed 54 recent reports focused on the contribution
      of genetic polymorphisms to the risk of developing leukemia and to disease
      progression. The polymorphisms of genes encoding drug-metabolising enzymes (CYP
      family, NQO1, GSTT1, GSTM1, GSTP1), enzymes involved in folate metabolism (MTHFR,
      TYMS, SHMT1, MTRR), and DNA repair enzymes (XPD, XPG, RAD51, XRCC1, XRCC3, CHEK2,
      ATM) were considered in the review. RESULTS: There was a good agreement on the
      influence of NQO1*2 polymorphism and those of the enzymes involved in DNA repair
      with the increased risk of therapy-related leukemia/myelodysplastic syndrome.
      Most studies found a strong association between the polymorphisms MTHFR, C677T or
      A1298C, and NQO1*2 or *3 and the risk of acute lymphoblastic leukemia (ALL). In
      addition, most of the studies reported an association between GSTT1 deletions and
      an increased risk of de novo acute myeloid leukemia. In ALL, polymorphisms in the
      genes of folate metabolism are associated with poor prognosis, and the 3R3R TYMS
      polymorphism in particular is associated with methotrexate resistance.
      CONCLUSION: The reports reviewed support the hypothesis that several low
      penetrance genes with multiplicative effects together with dietary effects,
      ambient exposition, and individual immune system responses, may account for the
      risk of leukaemia.

PMID- 17023047
TI  - Various domains of the B-cell regulatory molecule CD72 has diverged at different
      rates in mammals: cloning, transcription and mapping of porcine CD72.
AB  - We report the cloning of the porcine B-cell co-receptor CD72, as well as genomic
      mapping and examination of transcription. The B-cell receptor (BCR) complex
      mediates signalling upon antigen recognition by the membrane bound BCR. Several
      co-receptors modulate this signal positively or negatively. CD72 has been shown
      to be a negatively regulating BCR co-receptor. We isolated and sequenced three
      porcine CD72 transcript variants. Using a pig radiation hybrid panel we found the
      porcine CD72 gene to be located on chromosome 1q21-28 in a region syntenic to
      human chromosome 9. The porcine CD72 gene is highly transcribed in lymph node,
      thymus and lung tissues as well as in pulmonary alveolar macrophages. The
      predicted porcine CD72 polypeptide shows conservation of immunoreceptor tyrosine
      based inhibitory motifs and an extracellular C-type lectin domain. Compared to
      CD72 sequences from other mammals as well as from chicken, the polypeptide is
      highly conserved in the intracellular part and much less conserved in the
      extracellular part. We suggest that this difference might be due to the different
      nature of ligands and the constrains on these to co-evolve.

PMID- 17023048
TI  - Enhanced T-cell activation and T-cell-dependent IL-2 production by CD83+,
      CD25high, CD43high human monocyte-derived dendritic cells.
AB  - Although standardized protocols are widely used for the generation of monocyte
      derived immunostimulatory dendritic cells (DC(ims)), the inducibility of Th1
      cells by DC(ims) may considerably differ. As a measure for the quality of DC(ims)
      generated from an individual donor at a certain time point, CD83 is used in
      combination with HLA-DR and CD86 to assess DC maturation. When phenotypically
      analyzing DC(ims), we identified a subpopulation ( approximately 60%) of CD83+,
      CD86+, and HLA-DR+ DC(ims) that co-expressed CD25. DC within a given DC(ims)
      preparation identified by lower expression of CD83 and by selective expression of
      CD14, however, did not co-express CD25. In order to establish CD25 as an
      additional maturation marker of DC(ims), we studied the DC phenotype of these
      cells as well as the DC-dependent T-cell proliferation and T-cell cytokine
      production profile after co-incubation with sorted CD25(high) and CD25(low)
      subpopulations of CD83+, HLA-DR+, CD86+ DC(ims). CD25(high) DC(ims) showed
      significant up-regulation of the DC activation molecule CD43 and induced
      increased levels of IL-2 secretion in allogeneic T-cells (170.7+/-86.7pg/mL) as
      compared to T-cells coincubated with CD25(low) DC(ims) (86.6+/-37.6pg/mL)
      [p=0.0224]. This was reflected by a significantly lower T-cell stimulatory
      capacity of CD25(low) DC(ims) (84.0% of CD25(high) DC(ims), 1:10 ratio; p=0.014)
      whereas the T-cell stimulatory capacity of CD25(low) DC(ims) was much higher when
      compared to IL-10 induced regulatory DC (55.3% of CD25(high) DC(ims); 1:10
      ratio). With regard to cancer vaccination protocols, we propose to use CD25 and
      CD43 as additional markers for DC quality control, assessment of maturational
      status, and positive selection.

PMID- 17023050
TI  - Contribution of noninvasive cortical stimulation to the study of memory
      functions.
AB  - In the memory domain, a large body of experimental evidence about subsystems of
      memory has been collected from classic lesion studies and functional brain
      imaging. Animal studies have provided information on molecular mechanisms of
      memory formation. Compared to this work, transcranial magnetic stimulation and
      transcranial direct current stimulation have made their own unique contribution.
      Here, we describe how noninvasive brain stimulation has been used to study the
      functional contribution of specific cortical areas during a given memory task,
      how these techniques can be used to assess LTP- and LTD-like plasticity in the
      living human brain, and how they can be employed to modulate memory formation in
      humans, suggesting an adjuvant role in neurorehabilitative treatments following
      brain injury.

PMID- 17023049
TI  - Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C
      exhibits heightened sensitivity to dysregulation by non-coplanar 2,2',3,5',6
      pentachlorobiphenyl (PCB 95).
AB  - Malignant hyperthermia (MH) susceptibility is conferred by inheriting one of >60
      missense mutations within the highly regulated microsomal Ca(2+) channel known as
      ryanodine receptor type 1 (RyR1). Although MH susceptible patients lack overt
      clinical signs, a potentially lethal MH syndrome can be triggered by exposure to
      halogenated alkane anesthetics. This study compares how non-coplanar 2,2',3,5',6
      pentachlorobiphenyl (PCB 95), a congener identified in environmental and human
      samples, alters the binding properties of [(3)H]ryanodine to RyR1 in vitro.
      Junctional sarcoplasmic reticulum (SR) was isolated from skeletal muscle
      dissected from wild type pigs ((Wt)RyR1) and pigs homozygous for MH mutation
      R615C ((MH)RyR1), a mutation also found in humans. Although the level of (Wt)RyR1
      and (MH)RyR1 expression is the same, (MH)RyR1 shows heightened sensitivity to
      activation and altered regulation by physiological cations. We report here that
      (MH)RyR1 shows more pronounced activation by Ca(2+), and is less sensitive to
      channel inhibition by Ca(2+) and Mg(2+), compared to (Wt)RyR1. In a buffer
      containing 100nM free Ca(2+), conditions typically found in resting cells, PCB 95
      (50-1000nM) enhances the activity of (MH)RyR1 whereas it has no detectable effect
      on (Wt)RyR1. PCB 95 (2microM) decreases channel inhibition by Mg(2+) to a greater
      extent in (MH)RyR1 (IC(50) increased nine-fold) compared to (Wt)RyR1 (IC(50)
      increased by 2.5-fold). PCB95 reduces inhibition by Ca(2+) two-fold more with
      (MH)RyR1 than (Wt)RyR1. Our data suggest that non-coplanar PCBs are more potent
      and efficacious toward (MH)RyR1 than (Wt)RyR1, and have more profound effects on
      its cation regulation. Considering the important roles of Ca(2+) and Mg(2+) in
      regulating Ca(2+) signals involving RyR channels, these data provide the first
      mechanistic evidence that a genetic mutation known to confer susceptibility to
      pharmacological agents also enhances sensitivity to an environmental contaminant.

PMID- 17023051
TI  - Quality of life in unaffected twins discordant for affective disorder.
AB  - BACKGROUND: The disability and hardship associated with affective disorder is
      shared by the family members of affective patients and might affect the family
      member's quality of life. METHOD: In a cross-sectional, high-risk, case-control
      study, monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and
      without (the control group/Low-Risk twins) a co-twin history of affective
      disorder were identified through nationwide registers. The aim of the present
      study was to investigate the hypothesis that a genetic liability to affective
      disorder is associated with a lower perception of quality of life. RESULTS:
      Univariate analyses showed that quality of life in all domains was impaired for
      the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression
      analyses, the differences remained significant after adjustment for sex, age,
      marital status and years of education. Adjusted for the effect of subclinical
      anxiety and depressive symptoms, the differences were significant on the domain
      environment and total WHOQoL-BREF and marginally significant on the domain
      physical health and overall quality of life. LIMITATIONS: It is not possible from
      the cross-sectional analyses to distinguish between subsyndromal state and trait
      scores. CONCLUSIONS: Perceived health related quality of life might share common
      familial vulnerability with affective disorders. Having a co-twin with affective
      disorder seem to have a negative influence on quality of life of the healthy co
      twin and this influence might be due to the genetic liability to affective
      disorder. These findings need to be replicated in future family studies.

PMID- 17023052
TI  - Association of increased serum heat shock protein 70 and C-reactive protein
      concentrations and decreased serum alpha(2)-HS glycoprotein concentration with
      the syndrome of hemolysis, elevated liver enzymes, and low platelet count.
AB  - The primary aim of this study was to determine serum Hsp70 concentrations in
      HELLP syndrome. We measured also the serum concentrations of three acute phase
      proteins: C-reactive protein (CRP), alpha(2)-macroglobulin (AMG) and alpha(2)-HS
      glycoprotein (AHSG). Ten severe preeclamptic patients with HELLP syndrome, 20
      severe preeclamptic patients without HELLP syndrome and 20 normotensive, healthy
      pregnant women were included in this case-control study. Serum concentrations of
      Hsp70, CRP, AMG and AHSG were measured using an enzyme-linked immunosorbent assay
      (Hsp70), particle-enhanced immunoturbidimetric assay (CRP) and radial
      immunodiffusion (AMG, AHSG). The serum Hsp70 and CRP concentrations were
      significantly higher, whereas the serum AHSG concentration was significantly
      lower in the HELLP group (H) than the severe preeclamptic (P) and control (C)
      groups (median (25-75 percentile); Hsp70: 2.02 ng/ml (0.76-2.23) (H) versus 0.54
      ng/ml (0.47-0.79) (P), p<0.01, and 0.30 ng/ml (0.27-0.33) (C), p<0.001; CRP: 43.9
      mg/l (27.1-84.5) (H) versus 6.5 mg/l (2.7-10.7) (P), p<0.001, and 2.5 mg/l (1.1
      6.7) (C), p<0.001; AHSG: 588 microg/ml (492-660) (H) versus 654 microg/ml (576
      768) (P), p<0.05, and 738 microg/ml (666-804) (C), p<0.01, respectively). The
      serum AMG concentration did not differ between the study groups. In the HELLP
      group, there was a statistically significant negative correlation between serum
      Hsp70 concentration and platelet count (Spearman R=-0.69, p=0.026). In
      conclusion, serum Hsp70 and CRP concentrations are increased, whereas serum AHSG
      concentration is decreased, in HELLP syndrome. The maternal systemic inflammation
      seems to be more pronounced in HELLP syndrome than preeclampsia without HELLP
      syndrome, as suggested by the alterations in serum CRP and AHSG levels. However,
      it requires further investigation to determine whether these changes are causes
      or consequences of the disease.

PMID- 17023053
TI  - Long-term evolution of anti-ganglioside antibody levels in patient with chronic
      dysimmune neuropathy under IVIg therapy.
AB  - The authors retrospectively examined the anti-ganglioside antibody (AGA) IgM
      level changes from 14 patients with chronic dysimmune neuropathy (5 with
      multifocal motor neuropathy and 9 with chronic inflammatory demyelinating
      polyneuropathy) treated with maintenance doses of intravenous immunoglobulins
      (IVIg). The median follow-up was 5 years. At last follow-up, 93% of the patients
      had an increment of AGA levels, and five patients with initial AGA values within
      normal range became positive during follow-up. Overall, median AGA titers
      significantly increased from the first to the last samples, despite a substantial
      clinical stability after the initial improvement with IVIg. The AGA increment
      rate was inversely correlated with IVIg infusions interval necessary to maintain
      therapeutic efficacy. Thus, antibody testing in the follow-up of patients with
      dysimmune neuropathies may be helpful to predict the decline of IVIg efficacy and
      to identify those patients who eventually take advantage from an increase in
      infusion frequency.

PMID- 17023054
TI  - Frequency analysis of HLA-B7-restricted Epstein-Barr virus-specific cytotoxic T
      lymphocytes in patients with multiple sclerosis and healthy controls.
AB  - The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple
      sclerosis (MS), however, the mechanisms by which EBV may be involved in MS are
      unknown. We here have investigated the frequency of EBV-specific cytotoxic T
      lymphocytes (CTL) in human leukocyte antigen (HLA)-B7(+) patients with MS and
      healthy controls using enzyme-linked immunospot assays and seven previously
      characterized HLA-B7-restricted immunogenic EBV peptides. Overall, there were no
      significant differences in the frequency of EBV-specific CTL between both groups.
      These data do not support the hypothesis that EBV could play a role in MS by
      inducing quantitatively altered EBV-specific CTL responses. Other pathogenic
      mechanisms for EBV in MS remain to be elucidated.

PMID- 17023056
TI  - Neurotoxicity of vincristine on the medial olivocochlear bundle.
AB  - OBJECTIVE: Vincristine is a well known neurotoxic chemotherapeutic agent. Dose
      dependent and cumulative peripheral neuropathy is the main dose limiting side
      effect of chemotherapy with vincristine. The mechanisms responsible for the
      neurotoxic effects of vincristine have not yet been fully understood. This
      prospective study was directed at determining whether vincristine treatment
      interferes with the function of the medial olivocochlear bundle. DESIGN: Fifteen
      children suffering from leukemia were subjected to tympanogram, stapedial muscle
      reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs)
      in the absence and presence of contralateral white noise on day 1 and on day 22
      of treatment with vincristine. The function of the medial olivocochlear bundle
      was assessed by the phenomenon of suppression of otoacoustic emissions by
      contralateral application of white noise. RESULTS: The study revealed a
      statistically significant decrease of contralateral suppression amplitudes in all
      cases after three sessions of chemotherapy with vincristine. On the contrary no
      alterations were observed in pure tone audiometry thresholds. A non-significant
      decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by
      frequency, however, this decrease reached the level of statistical significance
      at two frequencies. CONCLUSION: Vincristine treatment seems to exert a neurotoxic
      effect on the efferent olivocochlear system, which takes place early in the
      course of chemotherapy. This is a new aspect to be added to the possible
      mechanisms underlying the toxicity of vincristine in the auditory periphery.
      Whether changes in efferent function might contribute to understanding the
      mechanisms of neurotoxicity caused by vincristine, or find any clinical
      application as a predictor or early detector of neurological side effects of
      vincristine still remains to be seen.

PMID- 17023055
TI  - Neurokinin 1 receptor signaling mediates sex differences in mu and kappa opioid
      induced enhancement of contact hypersensitivity.
AB  - Contact hypersensitivity (CHS) is a type of cutaneous inflammation that is
      exacerbated by neurogenic factors. Both mu- and kappa-opioids enhance CHS to a
      greater extent in females than males. It was hypothesized that potentiated
      neurokinin 1 (NK1) receptor signaling following opioid treatment accounts for sex
      differences in the magnitude of CHS. Following morphine or spiradoline treatment
      the NK1 receptor antagonist SR140,333 significantly attenuated the magnitude of
      CHS in females but not males. By contrast, the NK2 antagonist SR48968 had no
      effect on morphine modulation of CHS. Taken together, these data indicate that
      NK1 receptor signaling is a key mediator of sex differences in opioid-induced
      enhancement of CHS.

PMID- 17023057
TI  - Preliminary evidence of improved gaze stability following exercise in two
      children with vestibular hypofunction.
AB  - Despite impaired gaze stability and reading in children with sensorineural
      hearing loss (SNHL) and vestibular hypofunction (VH), there are no reports of
      intervention. We examined the effect of visual-vestibular exercises in two
      children on dynamic visual acuity (DVA), critical print size (CPS) and reading
      acuity (RA) using an ABA design. Improvement in CPS and RA was seen in both
      subjects. DVA improved only in the subject with acquired versus congenital VH.
      These results suggest that although exercise improves reading acuity, age at the
      time of lesion affects the improvement of DVA in children with SNHL and BVH.

PMID- 17023058
TI  - Bovine lactoferrin inhibits echovirus endocytic pathway by interacting with viral
      structural polypeptides.
AB  - Lactoferrin, an 80 kDa bi-globular iron-binding glycoprotein belonging to the
      transferrin family, is a pleiotropic factor with potent antimicrobial and
      immunomodulatory activities, present in breast milk, in mucosal secretions, and
      in the secondary granules of neutrophils. Recently, we have shown that bovine
      lactoferrin prevents the early phases of echovirus infection and also acts as a
      survival factor inhibiting viral-induced apoptosis. In the present research we
      investigated the mechanism of bovine lactoferrin anti-echoviral effect
      demonstrating that echovirus enters susceptible cells by an endocytic pathway and
      that lactoferrin treatment is able to prevent viral genome delivery into the
      cytoplasm. It is likely that lactoferrin interaction with echovirus capsid
      proteins induces alterations that stabilize the conformation of the virion making
      it resistant to uncoating. Taken together, the results of our study show that the
      inhibition of echovirus 6 infectivity by lactoferrin is dependent on its
      interaction not only with cell surface glycosaminoglycan chains but also with
      viral structural proteins demonstrating that this glycoprotein targets the virus
      entry process.

PMID- 17023059
TI  - Maternal adrenal hormone secretion mediates behavioural alterations induced by
      prenatal stress in male and female rats.
AB  - Prenatal stress in rats has been shown to impair the regulation of the
      hypothalamic pituitary adrenal (HPA) axis and predispose to anxiogenic and
      depressive-like behaviour. In a previous study, abolition of excess
      corticosterone (COR) release during stress by maternal adrenalectomy prevented
      the dysregulation of the HPA axis. In the present study, we determined whether
      excess maternal COR is also responsible for the alterations in offspring
      behaviour. Pregnant Wistar rats were adrenalectomized or sham-operated on day 11
      of gestation and subjected once daily to mild restraint for 30 min on days 14-21
      of gestation. An undisturbed group of pregnant females served as controls. All
      experiments were performed in male and female offspring. Pup weight and
      anogenital distance of males were measured after birth; anxiogenic behaviour was
      assessed in the elevated plus maze (EPM) at the age of 5 weeks and spatial memory
      in the Morris water maze in littermates at 3-4 months. Prenatally stressed (PS)
      males did not show a reduction in anogenital distance, and their increase in
      anxiogenic behaviour in the EPM was less than that in PS females. On the other
      hand, impairment of spatial learning was only seen in PS males. Both the
      anxiogenic behaviour of PS males and females and the learning deficit in males
      were completely abolished by adrenalectomy. These data show that excess stress
      induced COR can alter the programming of the foetal brain and predispose it to
      alterations in behaviour that are gender specific.

PMID- 17023060
TI  - Appetitive sensitization by amphetamine does not reduce its ability to produce
      conditioned taste aversion to saccharin.
AB  - Previous exposure to amphetamine attenuates its ability to induce conditioned
      taste aversion (CTA). Because amphetamine, unlike emetic agents like LiCl,
      possesses appetitive properties that sensitize when it is administered
      repeatedly, the present study assessed the contribution of sensitization to this
      US-pre-exposure effect (US-PEE). It was found that not all sensitizing regimens
      of systemic amphetamine injections produce a US-PEE. In addition, previous
      exposure to amphetamine in the VTA, where it acts to induce sensitization but not
      CTA, did not produce a US-PEE. It is concluded that amphetamine sensitization
      alone does not modulate this drug's ability to produce CTA. Implications of these
      findings for anatomically based associative and non-associative models of CTA and
      the US-PEE are discussed.

PMID- 17023061
TI  - Effects of unpredictable chronic mild stress on anxiety and depression-like
      behavior in mice.
AB  - The widely accepted stress-diathesis hypothesis of depression postulates that
      genetic factors contribute to biological vulnerability. Based on this concept,
      the unpredictable chronic mild stress (UCMS) animal model was developed. Most
      effects of UCMS can be reversed by antidepressant agents, illustrating a strong
      predictive validity. In rodents, UCMS also has good face validity as it can
      elicit depression-like symptoms. While abundant for rats, the UCMS literature on
      mice is relatively limited. Reports sometimes are contradictory, making it
      difficult to establish a clear profile of stress-induced depression-like
      behaviors in mice. As different groups often use different strains for their
      experiments, differential strain susceptibility to UCMS may provide at least a
      partial explanation of these discrepancies. Moreover, differences in testing
      methodology add another level of complexity. Very little is known about the role
      of genetic factors and their interactions with the environment in the development
      of stress-induced behavioral changes relevant to depression, though recent
      studies unequivocally demonstrated the effects of specific gene polymorphisms on
      stress-induced depressive symptoms, as well as the effects of stress on gene
      expression. In the present study, we investigated the effects of UCMS on a
      battery of different tests measuring anxiety and depression-like behaviors in
      three behaviorally and genetically distinct inbred strains. The goals of these
      experiments are to obtain a clearer behavioral profile of
      genetically/phenotypically distant mouse strains after UCMS treatment and to
      evaluate the limitations and strengths of the UCMS model in mice.

PMID- 17023062
TI  - Patterns of gene expression in carp liver after exposure to a mixture of
      waterborne and dietary cadmium using a custom-made microarray.
AB  - Gene expression changes in carp liver tissue were studied after acute (3 and 24h)
      and subchronic (7 and 28 days) exposure to a mixture of waterborne (9, 105 and
      480 microg/l) and dietary (9.5, 122 and 144 microg/g) cadmium, using a custom
      made microarray. Suppression subtractive hybridization-PCR (SSH-PCR) was applied
      to isolate a set of 643 liver genes, involved in multiple biological pathways,
      such as energy metabolism (e.g. glucokinase), immune response (e.g. complement
      C3) and stress and detoxification (e.g. cytochrome P450 2F2, glutathione-S
      transferase pi). These genes were subsequently spotted on glass-slides for the
      construction of a custom-made microarray. Resulting microarray hybridizations
      indicated a highly dynamic response to cadmium exposure. At low exposure
      concentrations (9 microg/l through water and 9.5 microg/g dry weight through
      food) mostly energy-related genes (e.g. glucokinase, elastase) were influenced,
      while a general stress response was obvious through induction of several stress
      related genes, including hemopexin and cytochrome P450 2F2, at high cadmium
      concentrations. In addition, fish exposed to the highest cadmium concentrations
      showed liver damage after 7 days of exposure, as measured by elevated alanine
      transaminase activity in plasma and increased liver water content (wet-to-dry
      weight ratio). Moreover, decreased hematocrit and growth were found at the end of
      the experiment. Altogether this study clearly demonstrated the importance of
      varying exposure conditions for the characterization of the molecular impact of
      cadmium and showed that microarray results can provide important information,
      required to unravel the molecular events and responses related to cadmium
      exposure.

PMID- 17023063
TI  - Lipids and lipid domains in the peroxisomal membrane of the yeast Yarrowia
      lipolytica.
AB  - Biological membranes have unique and highly diverse compositions of their lipid
      constituents. At present, we have only partial understanding of how membrane
      lipids and lipid domains regulate the structural integrity and functionality of
      cellular organelles, maintain the unique molecular composition of each organellar
      membrane by orchestrating the intracellular trafficking of membrane-bound
      proteins and lipids, and control the steady-state levels of numerous signaling
      molecules generated in biological membranes. Similar to other organellar
      membranes, a single lipid bilayer enclosing the peroxisome, an organelle known
      for its essential role in lipid metabolism, has a unique lipid composition and
      organizes some of its lipid and protein components into distinctive assemblies.
      This review highlights recent advances in our knowledge of how lipids and lipid
      domains of the peroxisomal membrane regulate the processes of peroxisome assembly
      and maintenance in the yeast Yarrowia lipolytica. We critically evaluate the
      molecular mechanisms through which lipid constituents of the peroxisomal membrane
      control these multistep processes and outline directions for future research in
      this field.

PMID- 17023064
TI  - Protein oxidation and cellular homeostasis: Emphasis on metabolism.
AB  - Reactive oxygen species (ROS) are generated as the result of a number of
      physiological and pathological processes. Once formed ROS can promote multiple
      forms of oxidative damage, including protein oxidation, and thereby influence the
      function of a diverse array of cellular processes. This review summarizes the
      mechanisms by which ROS are generated in a variety of cell types, outlines the
      mechanisms which control the levels of ROS, and describes specific proteins which
      are common targets of ROS. Additionally, this review outlines cellular processes
      which can degrade or repair oxidized proteins, and ultimately describes the
      potential outcomes of protein oxidation on cellular homeostasis. In particular,
      this review focuses on the relationship between elevations in protein oxidation
      and multiple aspects of cellular metabolism. Together, this review describes a
      potential role for elevated levels of protein oxidation contributing to cellular
      dysfunction and oxidative stress via impacts on cellular metabolism.

PMID- 17023065
TI  - The significance of peroxisomes in methanol metabolism in methylotrophic yeast.
AB  - The capacity to use methanol as sole source of carbon and energy is restricted to
      relatively few yeast species. This may be related to the low efficiency of
      methanol metabolism in yeast, relative to that of prokaryotes. This contribution
      describes the details of methanol metabolism in yeast and focuses on the
      significance of compartmentalization of this metabolic pathway in peroxisomes.

PMID- 17023066
TI  - Metabolic functions of glycosomes in trypanosomatids.
AB  - Protozoan Kinetoplastida, including the pathogenic trypanosomatids of the genera
      Trypanosoma and Leishmania, compartmentalize several important metabolic systems
      in their peroxisomes which are designated glycosomes. The enzymatic content of
      these organelles may vary considerably during the life-cycle of most
      trypanosomatid parasites which often are transmitted between their mammalian
      hosts by insects. The glycosomes of the Trypanosoma brucei form living in the
      mammalian bloodstream display the highest level of specialization; 90% of their
      protein content is made up of glycolytic enzymes. The compartmentation of
      glycolysis in these organelles appears essential for the regulation of this
      process and enables the cells to overcome short periods of anaerobiosis.
      Glycosomes of all other trypanosomatid forms studied contain an extended
      glycolytic pathway catalyzing the aerobic fermentation of glucose to succinate.
      In addition, these organelles contain enzymes for several other processes such as
      the pentose-phosphate pathway, beta-oxidation of fatty acids, purine salvage, and
      biosynthetic pathways for pyrimidines, ether-lipids and squalenes. The enzymatic
      content of glycosomes is rapidly changed during differentiation of mammalian
      bloodstream-form trypanosomes to the forms living in the insect midgut. Autophagy
      appears to play an important role in trypanosomatid differentiation, and several
      lines of evidence indicate that it is then also involved in the degradation of
      old glycosomes, while a population of new organelles containing different enzymes
      is synthesized. The compartmentation of environment-sensitive parts of the
      metabolic network within glycosomes would, through this way of organelle renewal,
      enable the parasites to adapt rapidly and efficiently to the new conditions.

PMID- 17023067
TI  - Peroxisome biogenesis: where Arf and coatomer might be involved.
AB  - The present review summarizes recent observations on binding of Arf and COPI coat
      to isolated rat liver peroxisomes. The general structural and functional features
      of both Arf and coatomer were considered along with the requirements and
      dependencies of peroxisomal Arf and coatomer recruitment. Studies on the
      expression of mammalian Pex11 proteins, mainly Pex11alpha and Pex11beta,
      intimately related to the process of peroxisome proliferation, revealed a
      sequence of individual steps including organelle elongation/tubulation, formation
      of membrane and matrix protein patches segregating distinct proteins from each
      other, development of membrane constrictions and final membrane fission. Based on
      the similarities of the processes leading to cargo selection and concentration on
      Golgi membranes on the one hand and to the formation of peroxisomal protein
      patches on the other hand, an implication of Arf and COPI in distinct processes
      of peroxisomal proliferation is hypothesized. Alternatively, peroxisomal Arf/COPI
      might facilitate the formation of COPI-coated peroxisomal vesicles functioning in
      cargo transport and retrieval from peroxisomes to the ER. Recent observations
      suggesting transport of Pex3 and Pex19 during early steps of peroxisome
      biogenesis from the ER to peroxisomes inevitably propose such a retrieval
      mechanism, provided the ER to peroxisome pathway is based on transporting
      vesicles.

PMID- 17023068
TI  - Proteolytic cleavage of annexin 1 by human leukocyte elastase.
AB  - Annexin 1 has been shown to participate through its unique N-terminal domain in
      the recruitment and activation of leukocytes at sites of inflammation. Peptides
      derived from this domain are true mimetics of the annexin 1 action in all
      inflammation models tested and most likely serve as the active entities generated
      at sites of inflammation. To elucidate mechanisms underlying peptide generation
      we used isolated blood leukocytes and endothelial cell monolayers. We show that
      following endothelial adhesion, annexin 1 was externalized from leukocytes and
      rapidly cleaved. Addition of purified annexin 1 to degranulating leukocytes
      resulted in the truncation of annexin 1, which seemed to depend on the
      proteolytic activity of human leukocyte elastase (HLE). The capacity of elastase
      to proteolytically cleave annexin 1 was confirmed using both purified annexin 1
      and HLE. The identification of annexin 1 as a substrate for HLE supports the
      model in which annexin 1 participates in regulating leukocyte emigration into
      inflamed tissue through N-terminal peptides generated at inflammatory sites.

PMID- 17023069
TI  - The evolution of calcium biochemistry.
AB  - The role of calcium in evolution is best understood from a perspective based on
      its intrinsic value as a divalent cation able to bind and precipitate inorganic
      and organic anions rapidly. This binding can be useful or inhibitory. Now
      treatment of binding or precipitation has two different interests in biological
      cells. The first is thermodynamic, that is the stress is on systems biology and
      the second is structure, that is molecular biology. In evolution both have equal
      weight being connected through exchange. This paper outlines first the systems
      biology of the evolution of calcium functions from prokaryotes to animals with
      brains. The calcium ion was the only good available candidate in the environment
      for the functions it performs. The second section of the paper describes the
      evolution of the proteins which allow the messenger function. We have discussed
      elsewhere the structure/function relationships of the proteins. Overall the
      evolving and increasing involvement of calcium as possibly the major control
      messenger of events outside cells to action inside them is an inevitable feature
      of the nature of ecological, that is environmental/organism, evolution.

PMID- 17023070
TI  - Warfarin interaction with herbal drugs and food.

PMID- 17023071
TI  - Pregnancy and delivery in patient after Fontan's operation due to common
      ventricle of left ventricular morphology.
AB  - Five pregnancies in a woman with functionally single ventricle of left ventricle
      morphology after Fontan's operation were described. Two pregnancies resulted in
      delivery of healthy, mature neonate. The patient's clinical status remained
      unchanged.

PMID- 17023072
TI  - Influence of high homocysteine and low folate plasmatic levels in medium-term
      prognosis after acute coronary syndromes.
AB  - BACKGROUND: To test prospectively whether moderate hyperhomocysteinemia and low
      folate levels could have an influence in the prognosis of 155 patients who
      presented with an acute coronary syndrome. METHODS AND RESULTS: After a mean
      follow-up of 13.4+/-7.4 months, patients with low folate levels had higher
      percentages of cardiovascular death and major cardiovascular events (33% vs. 5%,
      p<0.001; 44% vs. 22%, p<0.05) and patients with high homocysteine levels had a
      higher percentage of major cardiovascular events (31% vs. 14.5%, p<0.03). Kaplan
      Meier survival estimates analysis showed that patients with low folate levels had
      a significantly higher probability of cardiovascular death and lower free-of
      events survival (log rank statistic: 21.17, p<0.001 and 6.59, p=0.01). Patients
      with high homocysteine levels had a lower free-of-events survival (log rank
      statistic: 4.95, p=0.02). Different survival multivariate analysis model showed
      that the presence of low folate levels was an independent predictor of
      cardiovascular death (hazard ratio 8.85, 95% confidence interval 2.6-29.3,
      p<0.000) and high homocysteine levels was identified as independent predictor of
      major cardiovascular events (hazard ratio 2.34, 95% confidence interval 1.07
      5.12, p<0.03). CONCLUSIONS: Low folate levels and moderate hyperhomocysteinemia
      were identified as independent predictors of cardiovascular events in the follow
      up.

PMID- 17023073
TI  - Noncontact three-dimensional mapping guides catheter ablation of difficult
      atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most
      common supraventricular tachycardia in adulthood. Although selective ablation of
      the slow AV nodal pathway can cure AVNRT, accidental AV block may occur. The
      details on the electrophysiologic characteristics, quantitative data on the
      voltage inside Koch's triangle, and the use of three-dimensional noncontact
      mapping to facilitate the catheter ablation of AVNRT associated with a high-risk
      for AV block or other arrhythmias have been limited. METHODS AND RESULTS: Nine
      patients (M/F=5/4, 34+/-23 years, range 17-76) with clinically documented AVNRT
      were included. All patients had undergone previous sessions for slow AV nodal
      pathway ablation but they had failed, because of repetitive episodes of complete
      AV block during the RF energy applications. Further, one patient had a complex
      anatomy and 4 patients were associated with other tachycardias, respectively. The
      electrophysiologic studies revealed that 4 patients had the slow-fast, 4 the slow
      intermediate and one the fast-intermediate form of AVNRT. Noncontact mapping
      demonstrated two types of antegrade AV nodal conduction, markedly differing sites
      of the earliest atrial activation during retrograde VA conduction, and a lower
      range of voltage within Koch's triangle. The lowest border of the retrograde
      conduction region was defined on the map, and the application of the RF energy
      was delivered below that border to prevent the occurrence of AV block. The
      distance between the successful ablation lesions and the lowest border of the
      retrograde conduction region was significantly shorter in the patients with the
      slow-intermediate form of AVNRT than in those with the slow-fast form (5.5+/-3.4
      vs. 15+/-7.6 mm; p<0.05). After the ablation procedure, either rapid pacing or
      extrastimulation could not induce any tachycardia, and there was no recurrence
      during the follow-up (10.3+/-5.4, 2 to 22 months). CONCLUSIONS: Noncontact
      mapping could effectively demonstrate the antegrade and retrograde atrionodal
      conduction patterns, electrophysiologic characteristics of Koch's triangle, and
      guide the successful catheter ablation in difficult AVNRT cases.

PMID- 17023074
TI  - Long-term prognosis after coronary bypass surgery depends on interleukin 6
      polymorphism and past acute infections.
AB  - We were seeking for a mutual link between the -174G>C IL6 promoter polymorphism,
      history of the past acute respiratory infections and the long-term post-coronary
      artery bypass grafting (CABG) major adverse cardiovascular events (MACE)
      incidence. Two hundred thirty seven post-CABG patients have been followed up for
      a median period of 36 months. We found that past acute infections, influenza-like
      illness and lack of vaccination against influenza confer a significant risk of
      the post-CABG MACE incidence in the -174G allele carrying patients.

PMID- 17023075
TI  - Circulating Chlamydia pneumoniae DNA and advanced coronary artery disease.
AB  - BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) has been linked to
      atherosclerosis. Detection of this pathogen in peripheral blood cells may be
      valuable in the diagnosis of disease state. This study aimed to evaluate the
      prevalence of circulating C. pneumoniae DNA and its relationship with severity
      and extent of coronary artery disease (CAD). METHODS: Blood samples from 269
      patients undergoing coronary angiography were collected. The presence of
      circulating C. pneumoniae DNA was determined by real-time PCR assay. Data
      regarding coronary risk factors and severity and extent of CAD were collected.
      Severity and extent of CAD was defined by the number of major epicardial coronary
      arteries with >50% stenosis and by the Duke jeopardy score. RESULTS: Sixteen of
      269 specimens (5.9%) from the study cohort were positive for C. pneumoniae DNA.
      Thirteen specimens among 149 samples from patients with multi-vessel disease
      (8.7%) were positive for C. pneumoniae DNA compared with 3 of 120 (2.5%) among
      patients without multi-vessel CAD. The prevalence of circulating C. pneumoniae
      DNA was significantly associated with multi-vessel disease. The odds ratio was
      5.1 (P=0.02) after adjustment for conventional risk factors. CONCLUSIONS:
      Presence of circulating C. pneumoniae DNA is associated with advanced CAD,
      suggesting C. pneumoniae infection as a contributing factor to progression of
      coronary atherosclerosis.

PMID- 17023076
TI  - A randomised controlled trial of cardiac rehabilitation after revascularisation.
AB  - BACKGROUND: It is unclear if psycho-education on top of physical training is of
      additional value regarding quality of life in revascularised patients. DESIGN:
      Prospective randomised study comparing two types of cardiac rehabilitation:
      exercise based versus a more comprehensive approach including psychological
      therapy. METHODS: One hundred and thirty-seven male patients who underwent an
      uncomplicated coronary revascularisation procedure and who were mentally in a
      good condition, were randomised to one of two types of cardiac rehabilitation:
      physical training plus information about their disease ('Fit' program) during 6
      weeks or comprehensive cardiac rehabilitation which, on top of the Fit-program,
      included weekly psycho-education sessions and relaxation therapy ('Fit-Plus'
      program) for 8 weeks. One hundred and four patients were analysed. Quality of
      life was measured by the 'Leiden Quality of Life questionnaire' and by the RAND
      36 (quality of life) questionnaire. RESULTS: Quality of life improved in both
      treatment groups in the course of time up to 9 months after cardiac
      rehabilitation and there was no difference between the two types of cardiac
      rehabilitation. Exercise capacity improved likewise, blood lipid profile was
      unaffected and energy intake decreased in each treatment group but, again, there
      were no inter-group differences. CONCLUSION: After an uncomplicated
      revascularisation procedure, physical training plus information results in a
      comparable outcome on quality of life when compared to a more comprehensive
      program including additional psycho-education and relaxation therapy.

PMID- 17023077
TI  - Homocysteine and outcome in young patients with acute coronary syndromes.
AB  - BACKGROUND: Despite the well-known pro-thrombotic and pro-inflammatory plasma
      homocysteine effects, it remains uncertain whether these effects can be
      associated with an adverse cardiac outcome in young patients admitted with acute
      coronary syndromes. METHODS: Homocysteine levels were determined within 24 h
      after admission in 244 consecutive patients aged less than 56 years who presented
      with an acute coronary syndrome. We evaluated the relationship between
      homocysteine and both short-term (death, myocardial [re]infarction), and long
      term prognosis (death, recurrent acute coronary syndrome and/or ischemic stroke),
      after 3.4+/-1.7 years of follow-up. RESULTS: Homocysteine levels were similar in
      patients both with and without in-hospital event: 8.65 (5.36-10.48) vs. 8.98
      (7.38-11.13) micromol/l, p=NS. However, patients who presented with the combined
      event during follow-up had higher homocysteine levels than those free of the
      event: 10.54 (7.90-11.76) micromol/l vs. 8.52 (7.11-10.23) micromol/l, p=0.001.
      Patients who either died (13.78 vs. 8.87 micromol/l, p=0.012) or had a myocardial
      infarction (10.75 vs. 8.76 micromol/l, p=0.006) or unstable angina (10.46 vs.
      8.76, p=0.006) during follow-up had higher homocysteine levels. According to the
      Cox regression analysis: age [hazard ratio 1.05, CI 95%, 0.99-1.10], left
      ventricular ejection fraction < or =40% [hazard ratio 1.93, CI 95%, 0.98-3.79],
      and homocysteine tertile 3 [hazard ratio 2.05, CI 95%, 1.13-3.71] were the
      significant determinants of the combined adverse event during follow-up. Although
      41 (18%) of patients presented the TT genotype of the methylen-tetrahydrofolate
      reductase thermolabile variant mutation, its occurrence had a neutral effect on
      morbid-mortality. CONCLUSIONS: High homocysteine levels at admission strongly
      predict late cardiac events in young patients with acute coronary syndromes.

PMID- 17023078
TI  - Lack of association between the platelet glycoprotein Ia C807T gene polymorphism
      and coronary artery disease: a meta-analysis.
AB  - BACKGROUND: The platelet-collagen receptor, glycoprotein (GP) la/lla plays a
      crucial role in the adhesion of platelets to fibrillar collagen, an event
      contributing to the pathogenesis of thrombosis. The C807T polymorphism of the
      GPla gene is considered a genetic marker of the platelet GPla/lla density. The
      importance of the GPla gene C807T polymorphism as a genetic risk factor for
      coronary artery disease (CAD) remains controversial. To assess this association,
      we performed a meta-analysis of published data. METHODS: A comprehensive meta
      analysis of 19 studies, with a total sample of 13835 subjects using random
      effects models. RESULTS: The C versus T allele contrast gave an OR of 0.998 with
      95% Cl 0.937-1.064. Similarly, comparing the C homozygotes with the T
      homozygotes, the CC genotype versus the others and the TT genotype versus the
      rest, no evidence of any gene-disease association was obtained. Furthermore, the
      meta-regression analysis did not disclose any variable that could modify the role
      of this polymorphism in the development of CAD. CONCLUSION: Our findings support
      the view that C807T polymorphism of the GPla gene is not a significant risk
      factor for CAD, either alone or in combination with other major cardiovascular
      risk factors.

PMID- 17023079
TI  - Cardiologic and neurologic findings in left ventricular
      hypertrabeculation/noncompaction relating to echocardiographic indication.
AB  - BACKGROUND: Left-ventricular hypertrabeculation/noncompaction (LVHT) is
      characterized by prominent trabeculations and intertrabecular recesses. LVHT is
      usually diagnosed if a patient is referred for echocardiography. The study
      assessed if cardiologic and neurologic findings differ relating to indication for
      echocardiography. METHODS: Included were patients in whom LVHT was diagnosed in
      one echocardiographic laboratory between June 1995 and December 2005. All
      patients underwent a cardiologic examination and were invited for a neurological
      investigation. RESULTS: LVHT was diagnosed in 93/35,181 patients (26 female, 53+/
      15 years). Heart failure was the most frequent indication (n=49), followed by
      chest pain (n=21), syncope (n=8), search for cardiac involvement in myopathy
      (n=7), stroke or embolism (n=3), arterial hypertension (n=3) and screening of
      LVHT patients' relatives (n=2). Patients with the indication "heart failure" were
      older than patients with other indications (59.4+/-13.1 versus 44.9+/-12.9 years,
      p<0.001), had more often a neuromuscular disorder of unknown etiology (53% versus
      32%, p<0.05), exertional dyspnoea (96% versus 32%, p<0.001), edema (25% versus
      7%, p<0.05) and advanced heart failure (NYHA III: 41% versus 11%, p<0.01; NYHA
      IV: 29% versus 9%, p<0.05), suffered less often from arterial hypertension (22%
      versus 41%, p<0.05), angina pectoris (14% versus 34%, p<0.05) and palpitations or
      syncope (10% versus 30%, p<0.05). Patients with the indication "heart failure"
      had less frequent normal ECG than patients with other indications (2% versus 18%,
      p<0.01), had more frequent > or = 2 ECG abnormalities (57% versus 36%, p<0.05),
      left bundle branch block (29% versus 9%, p<0.05), a larger left-ventricular
      enddiastolic diameter (69.9+/-9.7 versus 57.4+/-12.2 mm, p<0.001), a lower left
      ventricular fractional shortening (16.9+/-6.1% versus 31.1+/-11.5%, p<0.001) and
      more often valvular abnormalities (76% versus 30%, p<0.001). Location and
      extension of LVHT did not differ between indication groups. CONCLUSION:
      Echocardiographers should be aware of LVHT in any indication for
      echocardiography.

PMID- 17023080
TI  - Beta1-adrenergic receptor polymorphisms, QTc interval and occurrence of symptoms
      in type 1 of long QT syndrome.
AB  - BACKGROUND: The most prevalent LQT1 form of inherited long QT syndrome is caused
      by mutations of the KCNQ1 gene resulting repolarizing I(Ks) potassium current to
      decrease and the QT interval to prolong. As abrupt sympathetic activation
      triggers ventricular arrhythmias that may cause syncopal attacks and sudden death
      in LQT1 patients, we investigated whether two known beta1-adrenergic receptor
      polymorphisms were associated with the duration of QT interval or history of
      symptoms in LQT1. METHODS: We determined beta1-adrenergic receptor polymorphisms
      (Ser49Gly and Arg389Gly) in 168 LQT1 patients. We also reviewed each patient's
      clinical records on the history of long QT syndrome-related symptoms and measured
      QT intervals from baseline ECG in each subject and from an exercise test ECG in
      55 LQT1 patients. RESULTS: Patients with the homozygous Arg389Arg genotype tended
      to have shorter and those with the Ser49Ser genotype longer QT intervals than
      patients with other genotypes, but neither polymorphism studied alone affected
      the risk of symptoms. In contrast, adjusted odds ratio for the history of
      symptoms was 4.9 (95% CI 1.18 to 20.3) in patients homozygous for both Ser49 and
      Arg389. These double homozygous patients showed similar QT intervals as the rest
      of the LQT1 cohort. CONCLUSIONS: In this relatively small study, double
      homozygosity for Arg389 and Ser49 of the human beta1-adrenergic receptor
      associated with the risk of symptoms in LQT1. The association between these beta1
      adrenergic receptor polymorphisms and the symptom history in LQT1 is not mediated
      via QT interval duration.

PMID- 17023081
TI  - Leukocytosis and clinical outcomes in acute inferior myocardial infarction.

PMID- 17023082
TI  - Severe coronary artery disease in the setting of Henoch-Schoenlein purpura.

PMID- 17023083
TI  - A multi-level representation paradigm for handwriting stroke generation.
AB  - The study of rapid strokes is a direct or indirect prerequisite in many
      fundamental research projects, as well as in the design of many practical
      applications dealing with handwriting. This paper outlines a family of models,
      derived from the Kinematic Theory of Human Movements. It explains how the nested
      models in this family can be used coherently, in the context of a multi-level
      representation paradigm, to analyze both the trajectory and the velocity of
      strokes with a progressive amount of detail. In the context of a comprehensive
      survey of previously published work, this paper highlights many new features of
      stroke production, when the vectorial version of the theory is fully exploited.
      In this perspective, the Kinematic Theory is depicted as a potential tool to
      facilitate communications among researchers working in the multi-disciplinary
      field of Graphonomics.

PMID- 17023084
TI  - Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from
      patients co-infected with human immunodeficiency virus type 1.
AB  - The hepatitis C virus (HCV) genotype 4 is spreading among southern European
      intravenous drug users, who are frequently co-infected with human
      immunodeficiency virus type 1 (HIV-1). Response to interferon (IFN) alpha-based
      therapies in HIV-1 positive patients co-infected with HCV genotype 4 is poor,
      similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes
      2 and 3. The lack of sequence data related to HCV of genotype 4 prompted us to
      sequence the complete genome of two genotype 4 variants isolated from two HIV-1
      co-infected patients (24 and 25). Our aim was to investigate the evolutionary
      relationships of the former variants with other genotypes and/or genotype 4
      subtypes. Sequence alignments and phylogenetic analysis from genomic regions
      5'NC, core-E1 and NS5B revealed that the variants isolated from patients 24 and
      25 (both subtyped 4c/4d by INNO-LIPA II HCV) belong to subtypes 4d and 4a,
      respectively. When looking at the complete genome sequence one of the variants
      showed a new genotype 4 subtype. Interestingly, sequence length differences in
      the interferon sensitivity determining region coding regions were observed when
      compared with sequences from other genotypes. Similarly, when the catalytic
      efficiency of the NS3/4 protease from patients 24 and 25 samples were determined,
      they displayed 70.6+/-7.7 and 23.5+/-3.4%, respectively, of the activity shown by
      genotype 1 NS3/4 proteases. Overall, pairwise comparison and phylogenetic
      analysis of nucleotide sequences of the complete genome or the different protein
      encoding regions showed that genotype 4 sequences were more closely related to
      genotype 1 sequences. The description of new HCV genome variants may help our
      understanding of the HCV biology as well as the role of different genotypes in
      HCV treatment and therapy response.

PMID- 17023086
TI  - Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic
      patients.
AB  - OBJECTIVE: Osteoprotegerin (OPG) regulates osteoclast and immune functions and
      appears to represent a protective factor for vascular system. However, the role
      of OPG in endothelial dysfunction of type 1 diabetic patients has not been
      evaluated. The purpose of this study was to investigate the relationship between
      plasma OPG levels and endothelium-dependent arterial dilation in type 1 diabetic
      patients. RESEARCH DESIGN AND METHODS: This study subjects included 22 newly
      diagnosed type 1 diabetic patients and 28 healthy subjects. All patients were
      then given insulin therapy for 6 months. Plasma OPG concentration was measured in
      duplicate by a sandwich ELISA method, and high-resolution ultrasound was used to
      measure brachial artery diameter at rest, after reactive hyperemia and after
      sublingual glyceryltrinitrate (GTN). RESULTS: Plasma OPG level in patients before
      treatment was 3.09+/-0.70 ng/L, which was significantly higher than that in
      control (2.07+/-0.75 ng/L) (p<0.001). After 6 months treatment, OPG levels
      decreased markedly (2.58+/-0.59 ng/L) (p<0.001). The flow-mediated endothelium
      dependent arterial dilation in patients before treatment was 3.35+/-0.67%, which
      was significantly lower than that in control (5.17+/-0.83%) (p<0.001), and
      improved markedly after 6 months treatment (4.27+/-0.63%) (p<0.001). In
      multivariate analysis, OPG was significantly associated with endothelium
      dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c),
      and ultra sensitive C-reactive protein (CRP) at baseline (p<0.01). The absolute
      changes in OPG showed significant correlation with the changes in endothelium
      dependent arterial dilation, FBG, HbA1c, and CRP in diabetic patients during the
      course of treatment (p<0.01). CONCLUSION: This study shows that plasma OPG levels
      are elevated in newly diagnosed type 1 diabetic patients, and that plasma OPG
      levels are significantly associated with endothelial function.

PMID- 17023085
TI  - Positively charged polyethylenimines enhance nasal absorption of the negatively
      charged drug, low molecular weight heparin.
AB  - This study tests the hypothesis that positively charged polyethylenimines (PEIs)
      enhance nasal absorption of low molecular weight heparin (LMWH) by reducing the
      negative surface charge of the drug molecule. Physical interactions between PEIs
      and LMWH were studied by Fourier transform infrared (FTIR) spectroscopy, particle
      size analysis, conductivity measurements, zeta potential analysis, and azure A
      assay. The efficacy of PEIs in enhancing nasal absorption of LMWH was studied by
      administering LMWH formulated with PEI into the nose of anesthetized rats and
      monitoring drug absorption by measuring plasma anti-factor Xa activity. The
      metabolic stability of LMWH was evaluated by incubating the drug in rat nasal
      mucosal homogenates. FTIR spectra of the LMWH-PEI formulation showed a shift in
      peak position compared to LMWH or PEI alone. Decreases in conductivity, zeta
      potential and the amount of free LMWH in the PEI-LMWH formulation, as revealed by
      azure A assay, suggest that PEIs possibly neutralize the negative surface charge
      of LMWH. The efficacy of PEI in enhancing the bioavailability of nasally
      administered LMWH can be ranked as PEI-1000 kDa>or=PEI-750 kDa>PEI-25 kDa. When
      PEI-1000 kDa was used at a concentration of 0.25%, there was a 4-fold increase in
      both the absolute and relative bioavailabilities of LMWH compared to the control
      formulation. Overall, these results indicate that polyethylenimines can be used
      as potential carriers for nasally administered LMWHs.

PMID- 17023087
TI  - Averting iatrogenic hypoglycemia through glucose prediction in clinical practice:
      progress towards a new procedure in diabetes.
AB  - BACKGROUND: Hypoglycemia is a risk factor common to all insulin therapy. The
      hypothesis is that efforts to reduce or prevent this adverse side effect may fail
      because providers generally lack the resources to predict not only future blood
      glucose levels but also future risks of hypoglycemia. This lack has been
      remedied. A controlled study was undertaken to test the hypothesis. METHODS:
      Twenty-two insulin dependent subjects suffering more than one (1) episode/week of
      hypoglycemia with similar insulin regimens, similar diabetes education and
      similar self-management training participated in this study. For all subjects, a
      remote monitoring resource (registry and database) was used to capture daily SMBG
      and afford a return path for provider interventions and decision support.
      Identical telemedical methods were used which differed only for the provider
      either by the presence (prediction group) or by the absence (control group) of an
      on-screen, visual display of predicted glycemia and predicted risks of
      hypoglycemia. The study lasted 2 months. RESULTS: Over an average of 41 days from
      baseline to follow up and while using the glycemic prediction resource, providers
      intervened more effectively in the prediction group reducing rates of
      hypoglycemia nine-fold (P<0.0001) and insulin therapy by just -9 U/day (P<0.01).
      Mean pre-meal glycemia was not compromised. Over 61 days from baseline to final
      follow up but without glycemic predictions in the control group, providers'
      interventions were less effective and resulted in no net changes in rates of
      hypoglycemia, daily insulin therapy, or mean pre-meal glycemia. CONCLUSIONS:
      Given knowledge of future glycemia and future risks of hypoglycemia, providers in
      clinical practice can now avert iatrogenic hypoglycemia in less than 2 months. A
      shared diabetes data center furnishing remote data capture and decision support
      is fundamental to the implementation of this as a new clinical procedure in
      diabetes.

PMID- 17023088
TI  - Effect of a viscous fiber-containing nutrition bar on satiety of patients with
      type 2 diabetes.
AB  - To assess the satiety-promoting effect of a novel viscous fiber-containing
      nutrition bar, overweight and obese adult subjects with type 2 diabetes (n=99)
      were randomized into a double blind, crossover study. They were fed a 300kcal
      lunch consisting of viscous fiber-containing nutrition bars (VF) or commercial
      nutrition control bars designed for people with diabetes (CH). VF resulted in a
      27.1% increase in fullness (p<0.05), a 15.8% decrease in prospective consumption
      (p<0.001), and a 14.2% decrease in hunger (p<0.001) in the 120-240min post-lunch
      areas under the curve (AUC) compared to CH, but no differences were observed for
      nausea or thirst (p>0.05). Similar results were noted for 0-300min AUC values. VF
      were associated with greater frequencies and intensities of abdominal distention
      (p<0.001) and flatulence (p<0.001), and greater frequency of stools (p<0.001)
      compared to CH, but there were no differences in mean or maximum (loosest) stool
      consistency (p>0.05). Overall, these results suggest that VF could be a useful
      tool in weight management of type 2 diabetes.

PMID- 17023089
TI  - Inhaled cytokines and cytokine antagonists.
AB  - Cytokine and cytokine antagonist have provided novel and effective therapies for
      many human diseases. A number of approved cytokines including the interferons
      (alpha, beta and gamma), interleukin-2 (IL-2), granulocyte macrophage colony
      stimulating factor (GM-CSF) as well as novel cytokine antagonists have been
      administered by the pulmonary route for both local lung disease and as a non
      invasive method for systemic delivery. We review the published clinical
      experience of inhaled cytokines and cytokine antagonists. We discuss the
      limitations of the existing data and the type of clinical data desired to
      establish the advantages and safety of inhaled cytokines and cytokine
      antagonists.

PMID- 17023090
TI  - Axonal transports of tripeptidyl peptidase II in rat sciatic nerves.
AB  - Axonal transport of tripeptidyl peptidase II, a putative cholecystokinin
      inactivating serine peptidase, was examined in the proximal, middle, and distal
      segments of rat sciatic nerves using a double ligation technique. Enzyme activity
      significantly increased not only in the proximal segment but also in the distal
      segment 12-72h after ligation, and the maximal enzyme activity was found in the
      proximal and distal segments at 72h. Western blot analysis of tripeptidyl
      peptidase II showed that its immunoreactivities in the proximal and distal
      segments were 3.1- and 1.7-fold higher than that in the middle segment. The
      immunohistochemical analysis of the segments also showed an increase in
      immunoreactive tripeptidyl peptidase II level in the proximal and distal segments
      in comparison with that in the middle segment, indicating that tripeptidyl
      peptidase II is transported by anterograde and retrograde axonal flow. The
      results suggest that tripeptidyl peptidase II may be involved in the metabolism
      of neuropeptides in nerve terminals or synaptic clefts.

PMID- 17023091
TI  - Decreased serum and red blood cell kynurenic acid levels in Alzheimer's disease.
AB  - Kynurenine aminotransferases (KAT I and KAT II) are responsible for the
      transamination of kynurenine (KYN) to form kynurenic acid (KYNA), an excitatory
      amino acid receptor antagonist. Since these members of the kynurenine pathway
      (KP) are proposed to be involved in the pathogenesis of Alzheimer's dementia
      (AD), the activities of these enzymes and the levels of these metabolites were
      measured in the plasma and red blood cells (RBCs) of AD and control subjects
      together with the inheritance of the apolipoprotein (APOE) epsilon4 allele. KYNA
      levels were significantly decreased both in the plasma and in the RBCs in AD, but
      the levels of KYN and the activities of KAT I and KAT II remained unchanged. No
      association has been found with the possession of the epsilon4 allele. These
      findings indicate an altered peripheral KP in AD regardless of the APOE status of
      the probands.

PMID- 17023092
TI  - Apolipoprotein E polymorphism and dendritic shape in hippocampal interneurons.
AB  - The apolipoprotein E genetic polymorphism exerts a well described influence on
      Alzheimer's disease (AD) risk, although the pathogenetic mechanism is still not
      clear. Increasing evidence points to a diminished neuroplasticity in
      apolipoprotein E varepsilon4-allele carriers. But, alternatively or additionally,
      developmental differences in dendritic geometry may be associated with the
      polymorphism. We morphometrically examined the dendritic ramification of CA1
      Parvalbumin-positive GABAergic hippocampal neurons (n=571) in matched pairs of
      aged non-demented individuals with different apolipoprotein E genotype. We chose
      Parvalbumin-positive interneurons since they lack potentially confounding AD-like
      cytoskeletal changes. To minimize the risk of transneuronal dendritic changes due
      to significant deafferentation we focused on non-demented individuals. In this
      chosen paradigm, neither the disease-associated apolipoprotein E varepsilon4
      allele nor the apolipoprotein E varepsilon2-allele had a significant impact on
      dendritic shape when compared to the most common allelic variant apolipoprotein E
      varepsilon3/3. At least with respect to the studied cell type, the data suggest
      that the apolipoprotein E polymorphism does not modulate the original formation
      of dendrites in vivo, contrary to conclusions drawn from in vitro studies on
      neurite outgrowth.

PMID- 17023093
TI  - Neuron-specific susceptibility to apolipoprotein E4.

PMID- 17023094
TI  - Aging in the CNS: comparison of gray/white matter volume and diffusion tensor
      data.
AB  - This study investigated the global and regional effects of aging on brain volume,
      mean diffusivity (MD), and fractional anisotropy (FA) in 73 normal female
      subjects using voxel-based analysis. On a global scale, gray matter volume and FA
      were negatively correlated, whereas MD was positively correlated with age. Voxel
      wise analyses showed brain volume and FA were negatively correlated predominantly
      in anterior structures, whereas MD was positively correlated in the cortical gray
      matter and periventricular white matter. Volume preservation was observed in the
      cingulate gyrus and subjacent white matter. FA increase was observed in the
      putamen. Voxel-based direct comparisons of volume and diffusion properties showed
      FA was more strongly negatively correlated in the fronto-temporal white matter,
      compared with volume and MD. Stronger positive correlation of MD was observed in
      the thalamus, caudate nucleus, and midbrain and stronger negative correlation of
      brain volume was observed in the frontal lobe and basal ganglia, compared with
      the other. These results indicate that diffusion properties and brain volume are
      complementary markers to the effects of aging.

PMID- 17023095
TI  - Long-term immunogenicity and efficacy of a 9-valent conjugate pneumococcal
      vaccine in human immunodeficient virus infected and non-infected children in the
      absence of a booster dose of vaccine.
AB  - The long-term immunogenicity and vaccine efficacy (VE) of a 9-valent conjugate
      pneumococcal vaccine was studied in HIV infected and HIV non-infected children.
      VE against vaccine-serotype invasive pneumococcal disease following 6.16 years of
      follow-up persisted in HIV non-infected children (77.8%; 95% CI 34.4-92.5
      compared to 83% after 2.3 years of follow-up), and declined from 65% to 38.8%
      (95% CI -7.8 to 65.2) in HIV infected children. HIV non-infected vaccinees had
      equal (serotypes 4, 6B, 14, 19F) or greater (serotypes 9V, 18C, 23F) proportions
      of serotype-specific antibody concentrations of > or =0.2microg/ml to vaccine
      serotypes analyzed compared to HIV infected vaccinees at 5.3 years of age.

PMID- 17023096
TI  - Plasmodium falciparum anti-MSP1-19 antibodies induced by MSP1-42 and MSP1-19
      based vaccines differed in specificity and parasite growth inhibition in terms of
      recognition of conserved versus variant epitopes.
AB  - The C-terminal 42 kDa fragment (MSP1-42) and its smaller 19 kDa subfragment (MSP1
      19) of the Plasmodium falciparum merozoite surface protein, MSP1, are leading
      candidate malaria vaccines. Since the targets of protective immunity lie within
      the MSP1-19, we compared the anti-MSP1-19 antibodies induced by vaccination with
      recombinant MSP1-42 and MSP1-19. The specificities of the antibody responses were
      analyzed using five recombinant MSP1-19s expressing different naturally occurring
      variant amino acid residues. We observed dramatic differences in the
      specificities of the anti-MSP1-19 antibodies induced by the two vaccines. MSP1-42
      consistently induced crossreactive antibodies; whereas the antibodies induced by
      recombinant MSP1-19 were highly variable among animals in terms of recognition of
      conserved versus variant epitopes. Of the variant residues examined, only a
      subset significantly contributed as part of immunogenic B epitopes. MSP1-42
      consistently induced potent growth inhibitory antibodies that recognized
      conserved epitopes, leading to efficient inhibition of heterologous parasites. In
      contrast, MSP1-19 induced strong inhibitory antibody responses in only a subset
      of animals studied. In some of the MSP1-19 immunized animals, inhibition of
      homologous parasites may be due to recognition of inhibitory epitopes associated
      with the homologous variant residues, and the induction of antibodies to
      conserved inhibitory epitopes may not be efficiently achieved. These data suggest
      an advantage of using MSP1-42 over MSP1-19 based vaccines.

PMID- 17023097
TI  - Radiology quality assurance in a developing country setting: the 11-valent
      pneumococcal conjugate vaccine trial, Bohol, Philippines.
AB  - The endpoint used for a phase 3 pneumococcal conjugate vaccine (PCV) trial in
      Bohol, Philippines was radiographic consolidation. Only one (Bohol Regional
      Hospital, BRH) of the four surveillance hospitals had a quality control/quality
      assurance program (QC/QA) prior to the trial. QC/QA was initiated in the three
      private hospitals. Radiologists from BRH evaluated radiographs from all hospitals
      based on recommended standards. Four thousand nine hundred and eighty nine films
      were analyzed. In 2000, the proportion of good quality films was 65% and 29% in
      BRH and private hospitals, respectively. By 2004, these increased to 92% and 79%,
      respectively. Poor film quality was commonly due to absence of collimation and
      poor contrast. The regular QC/QA implementation was necessary to improve film
      quality and was particularly important in our PCV trial that used X-ray proven
      consolidation as an endpoint.

PMID- 17023098
TI  - Immunogenicity of a combination vaccine containing pneumococcal conjugates and
      meningococcal PorA OMVs.
AB  - The pre-clinical immunogenicity of a combination vaccine containing 13-valent
      pneumococcal conjugate (13vPnC) vaccine (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V,
      14, 18C, 19A, 19F and 23F conjugated to CRM197) and nine-valent meningococcal B
      PorA vaccine (NonaMen; serosubtypes P1.7,16; P1.5-1,2-2; P1.19,15-1; P1.5-2,10;
      P1.12-1,13; P1.7-2,4; P1.22,14; P1.7-1,1 and P1.18-1,3,6), and any potential
      immunological interference between pneumococcal and MenB components of the
      vaccine were evaluated. NIH mice were immunized twice subcutaneously with the
      vaccines combined in one syringe, or given individually. Combining 13vPnC vaccine
      with NonaMen vaccine in one syringe had no negative effect on the induced
      antibody response against any MenB serosubtypes compared to separate injection of
      the vaccines, and the anti-pneumococcal antibody responses were enhanced.
      Furthermore, co-administration of the combination vaccine with a combined
      diphtheria/tetanus/acellular pertussis/inactivated poliomyelitis
      vaccine/Haemophilus influenzae type b-TT conjugate (DTaP/IPV-Hib) vaccine to New
      Zealand white rabbits at a different injection site did not affect the anti
      pneumococcal polysaccharide and anti-PorA antibody titres. We conclude that no
      immunological interference was observed by combined administration of
      pneumococcal conjugate and meningococcal B vaccines in one syringe.

PMID- 17023100
TI  - Botulinum toxin A for treating muscular contractures in cephalic tetanus.
AB  - OBJECTIVE: This study reports the use of botulinum toxin for treatment of muscle
      contractures in a patient with cephalic tetanus. METHOD: Case report. RESULTS: An
      80-year-old woman was diagnosed with cephalic tetanus, with contractures of the
      masseter, sternocleidomastoid, trapezius, and levator scapulae muscles. After one
      month of conventional treatment good recovery was observed, but with persistence
      of the contractures of the sternocleidomastoid, trapezius and levator scapulae.
      These contractures were treated with botulinum toxin A (75IU in the right
      sternocleidomastoid, 25IU in the right trapezius; one month later 50IU in the
      left levator scapulae, 50IU in the right levator scapulae, 75IU in the left
      sternocleidomastoid; two months later 25IU in the left trapezius). Full recovery
      was observed. CONCLUSIONS: Local infiltration with botulinum toxin A appears to
      be an effective treatment for persistent muscle contracture in cephalic tetanus.

PMID- 17023101
TI  - An unreported variation of the course of peroneal artery during fibula flap
      harvest.
AB  - We describe a previously unreported anatomical variant of the peroneal artery
      that was found both on preoperative angiography and at operation to be related to
      the fibula only in its distal third. In contrast to previously reported
      variations, the artery began descending on the medial aspect of the fibula about
      26cm from the fibular head.

PMID- 17023099
TI  - Immune suppression of challenged vaccinates as a rigorous assessment of sterile
      protection by lentiviral vaccines.
AB  - We previously reported that an experimental live-attenuated equine infectious
      anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided
      protection from disease and detectable infection after virulent virus (EIAV(PV))
      challenge [Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, et al. A live
      attenuated equine infectious anemia virus proviral vaccine with a modified S2
      gene provides protection from detectable infection by intravenous virulent virus
      challenge of experimentally inoculated horses. J Virol 2003;77(13):7244-53;
      Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, et al. Discerning an
      effective balance between equine infectious anemia virus attenuation and vaccine
      efficacy. J Virol 2005;79(5):2666-77]. To determine if attenuated EIAV vaccines
      actually prevent persistent infection by challenge virus, we employed a 14-day
      dexamethasone treatment of vaccinated horses post-challenge to suppress host
      immunity and amplify replication levels of any infecting EIAV. At 2 months post
      challenge the horses were all protected from virulent-virus challenge, evidenced
      by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune
      suppression, 6/12 horses displayed clinical EIA. Post-immune suppression
      characterizations demonstrated that the attenuated vaccine evidently prevented
      detectable challenge virus infection in 50% of horses. These data highlight the
      utility of post-challenge immune suppression for evaluating persistent viral
      vaccine protective efficacy.

PMID- 17023102
TI  - Inflammatory papillary hyperplasia of the palate: treatment with carbon dioxide
      laser, followed by restoration with an implant-supported prosthesis.
AB  - Inflammatory papillary hyperplasia of the palate is a persistant non-neoplastic
      lesion that is normally caused by poorly fitting dentures and Candida infection.
      We describe a case that was managed primarily with topical miconazole, and
      complete removal of the old acrylic denture. A multidisciplinary approach between
      surgeon and prosthodontist was used that combined carbon dioxide laser followed
      by substitution of the old removable denture for a new implant-supported screw
      retained prosthesis. This avoided direct support of the prosthesis by the palatal
      mucosa and made oral hygiene easier. The treatment has resulted in complete
      remission and there has been no recurrence occurred during 3 years of follow-up.

PMID- 17023103
TI  - Osteochondroma of the glenoid fossa--a case report.
AB  - Osteochondroma of the facial skeleton is a rare tumour that is usually managed by
      maxillofacial surgeons. In countries where this service is not available, or is
      provided by inexperienced surgeons, the management is difficult. We describe a
      case of osteochondroma of the glenoid fossa that was managed by surgeons with
      experience in temporomandibular surgery.

PMID- 17023104
TI  - Corlett loop for microvascular reconstruction in a neck depleted of vessels.
AB  - Free tissue transfer has revolutionised reconstruction of the head and neck and
      there are currently few local factors that preclude its use. These include a lack
      of suitable recipient vessels in the area for microvascular anastomosis. We
      describe the use of a Corlett loop in which a temporary arteriovenous fistula
      (AVF) is created with a transposed cephalic vein to enable reconstruction of a
      mandibular defect with a fibular free flap.

PMID- 17023105
TI  - Preservation of the superficial lobe with tumours of the deep-lobe of the
      parotid.

PMID- 17023106
TI  - Rewarding effects of 3,4-methylenedioxymethamphetamine ("Ecstasy") in dominant
      and subordinate OF-1 mice in the place preference conditioning paradigm.
AB  - We tested the ability of 3,4-methylenedioxymethamphetamine (MDMA) to induce
      conditioned place preference (CPP) in dominant and subordinate OF-1 mice
      subjected to cohabitation and repeated sessions of agonistic confrontation, as
      well as in non-confronted mice. We selected doses of MDMA (2, 6, 10 mg/kg)
      previously reported to induce CPP in mice and we measured expression of c-Fos
      evoked by the treatments in non-confronted mice. MDMA induced c-Fos protein in
      several corticolimbic regions involved in drug-induced reward. Mice were exposed
      to brief sessions of agonistic confrontation on 5 consecutive days.
      Determinations of circulating hormones and drug conditioning tests were carried
      out on completion of the encounters. The results of hormone assays indicated that
      dominant mice had higher serum concentrations of testosterone, but lower levels
      of corticosterone, than submissive mice. Post-conditioning tests after drug
      conditioning (4 injections of MDMA or saline on alternate days) showed that MDMA
      significantly produced CPP at doses of 2 and 6 mg/kg, but not at 10 mg/kg, an
      inverted U-shaped pattern of conditioning that was invariable in non-confronted,
      dominant and subordinate mice. These results demonstrate that the endocrine and
      behavioural correlates linked to social status and social stress in mice are not
      paralleled by significant changes in the rewarding efficacy of MDMA in the CPP
      paradigm under the specific conditions tested.

PMID- 17023107
TI  - Effects of chlorpromazine on plasma membrane permeability and fluidity in the rat
      brain: a dynamic positron autoradiography and fluorescence polarization study.
AB  - Antipsychotic drugs have been widely used in psychiatry for the treatment of
      various mental disorders, but the underlying biochemical mechanisms of their
      actions still remain unclear. Although phenothiazine antipsychotic drugs have
      been reported to directly interact with the peripheral plasma membrane, it is not
      known whether these drugs actually affect plasma membrane integrity in the
      central nervous system. To clarify these issues, we investigated the effect of
      chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, on plasma
      membrane permeability in fresh rat brain slices using a dynamic positron
      autoradiography technique and [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) as a
      tracer. Treatment with CPZ (> or =100 microM) resulted in the leakage of
      [(18)F]FDG-6-phosphate, but not [(18)F]FDG, suggesting that the [(18)F]FDG-6
      phosphate efflux was not mediated by glucose transporters, but rather by plasma
      membrane permeabilization. The leakage of [(18)F]FDG-6-phosphate was followed by
      slower leakage of cytoplasmic lactate dehydrogenase, suggesting that CPZ could
      initially induce small membrane holes that enlarged with time. Furthermore, the
      addition of CPZ (> or =100 microM) caused a decrease in 1,6-diphenyl-1,3,5
      hexatriene fluorescence anisotropy, which implies an increase in membrane
      fluidity. CPZ loading dose-dependently increased both membrane permeability and
      membrane fluidity, which suggested the involvement of a perturbation of membrane
      order in the mechanisms of membrane destabilization induced by antipsychotic
      drugs.

PMID- 17023108
TI  - Haemodynamic effects of adrenaline (epinephrine) depend on chest compression
      quality during cardiopulmonary resuscitation in pigs.
AB  - BACKGROUND: Adrenaline (epinephrine) is used during cardiopulmonary resuscitation
      (CPR) based on animal experiments without supportive clinical data. Clinically
      CPR was reported recently to have much poorer quality than expected from
      international guidelines and what is generally done in laboratory experiments. We
      have studied the haemodynamic effects of adrenaline during CPR with good
      laboratory quality and with quality simulating clinical findings and the
      feasibility of monitoring these effects through VF waveform analysis. METHODS AND
      RESULTS: After 4 min of cardiac arrest, followed by 4 min of basic life support,
      14 pigs were randomised to ClinicalCPR (intermittent manual chest compressions,
      compression-to-ventilation ratio 15:2, compression depth 30-38 mm) or LabCPR
      (continuous mechanical chest compressions, 12 ventilations/min, compression depth
      45 mm). Adrenaline 0.02 mg/kg was administered 30 s thereafter. Plasma adrenaline
      concentration peaked earlier with LabCPR than with ClinicalCPR, median (range),
      90 (30, 150) versus 150 (90, 270) s (p = 0.007), respectively. Coronary perfusion
      pressure (CPP) and cortical cerebral blood flow (CCBF) increased and femoral
      blood flow (FBF) decreased after adrenaline during LabCPR (mean differences (95%
      CI) CPP 17 (6, 29) mmHg (p = 0.01), FBF -5.0 (-8.8, -1.2) ml min(-1) (p = 0.02)
      and median difference CCBF 12% of baseline (p = 0.04)). There were no significant
      effects during ClinicalCPR (mean differences (95% CI) CPP 4.7 (-3.2, 13) mmHg (p
      = 0.2), FBF -0.2 (-4.6, 4.2) ml min(-1)(p = 0.9) and CCBF 3.6 (-1.8, 9.0)% of
      baseline (p = 0.15)). Slope VF waveform analysis reflected changes in CPP.
      CONCLUSION: Adrenaline improved haemodynamics during laboratory quality CPR in
      pigs, but not with quality simulating clinically reported CPR performance.

PMID- 17023109
TI  - Interview with Professor Ulf Tunn: LHRHa: What's new? Interview by Christine
      McKillop.

PMID- 17023110
TI  - The use of fish community structure as a measure of ecological degradation: a
      case study in two tropical rivers of India.
AB  - Fish community structure and water chemistry of two tropical rivers of West
      Bengal, an eastern province of India, were studied for two annual cycles (January
      2003-December 2004) and a higher degree of pollution was found in one river (the
      Churni) than in the other river (the Jalangi). This was reflected in the water
      quality as well as in fish community structure of the rivers. We observed that
      63.6% of fish species appeared to have been eliminated from the polluted Churni
      river since 1983 in 20 years. For the protection of fish biodiversity and
      enhancement of fish production, a rational management program should be
      implemented for the Churni river.

PMID- 17023111
TI  - Estrogen receptor beta (ERbeta) and inhibition of prostate cancer cell
      proliferation: studies on the possible mechanism of action in DU145 cells.
AB  - Estrogen receptor beta (ERbeta) plays a protective role against uncontrolled cell
      proliferation. ERbeta is lost during prostate cancer (CaP) progression suggesting
      its direct involvement in contrasting tumor proliferation in this disease;
      however, the molecular mechanism at the basis of this effect has not been clearly
      defined yet. Possible molecular targets of ERbeta were assessed in DU145 cells, a
      CaP cell line expressing only ERbeta. Cells treated from 1 to 9 days with
      different doses of estradiol or diarylpropionitrile (DPN, an ERbeta-selective
      agonist) show a time-dependent decrease in cell proliferation. The reduced
      proliferation rate is accompanied by the stimulation of ERbeta expression and the
      increase of cyclin-dependent kinase inhibitor p21. We demonstrate that the
      endogenous ERbeta is one of the mediator of the antiproliferative action of
      estrogens enhancing the synthesis of molecules such as p21 that control cell
      cycle, an effect amplified by the autoregulation of ERbeta expression. Our
      observations suggest that CaP, when expressing a functional ERbeta, might be
      sensitive to the antiproliferative action of estrogens; therefore, ERbeta
      specific agonists might be valid candidates for new pharmacological approaches to
      this disease.

PMID- 17023112
TI  - Influence of leachate recirculation on aerobic and anaerobic decomposition of
      solid wastes.
AB  - In this study, the effect of leachate recirculation on aerobic and anaerobic
      degradation of municipal solid wastes is determined by four laboratory-scale
      landfill reactors. The options studied and compared with the traditional
      anaerobic landfill are: leachate recirculation, landfill aeration, and aeration
      with leachate recirculation. Leachate quality is regularly monitored by the means
      of pH, alkalinity, total dissolved solids, conductivity, oxidation-reduction
      potential, chloride, chemical oxygen demand, ammonia, and total Kjeldahl
      nitrogen, in addition to generated leachate quantity. Aerobic leachate
      recirculated landfill appears to be the most effective option in the removal of
      organic matter and ammonia. The main difference between aerobic recirculated and
      non-recirculated landfill options is determined at leachate quantity.
      Recirculation is more effective on anaerobic degradation of solid waste than
      aerobic degradation. Further studies are going on to determine the optimum
      operational conditions for aeration and leachate recirculation rates, also with
      the operational costs of aeration and recirculation.

PMID- 17023113
TI  - Application of several advanced oxidation processes for the destruction of
      terephthalic acid (TPA).
AB  - Terephthalic acid (TPA) is widely applied as a raw material in making polyester
      fiber, polyethylene terephthalate (PET) bottles, polyester films, etc. TPA is
      toxic and is known to act as endocrine disruptor. TPA wastewater is traditionally
      treated by biological process and this study aims to evaluate the effectiveness
      of several advanced oxidation processes on TPA removal. The oxidation processes
      studied were: UV-TiO(2), UV-H(2)O(2), UV-H(2)O(2)-Fe, O(3), O(3)/Fe, O(3)/TiO(2),
      UV-O(3)-H(2)O(2)-Fe and UV-O(3)-H(2)O(2)-Fe-TiO(2). The results indicate that the
      time required for the complete destruction of 50 ppm of TPA can be minimized from
      10h using UV-TiO(2) system, to less than 10 min by UV-H(2)O(2)-Fe-O(3) system.
      Some of the likely organic intermediates identified during TPA destruction
      include, benzoquinone, benzene, maleic acid and oxalic acid. Possible destruction
      pathway of TPA has been proposed. TPA degradation by various systems was also
      analyzed based on the reaction kinetics and operating costs.

PMID- 17023114
TI  - Quenching of superoxide radicals by green fluorescent protein.
AB  - Green fluorescent proteins (GFP) are widely used in vivo molecular markers. These
      proteins are particularly resistant, and maintain function, under a variety of
      cellular conditions such as pH extremes and elevated temperatures. Green
      fluorescent proteins are also abundant in several groups of marine invertebrates
      including reef-forming corals. While molecular oxygen is required for the post
      translational maturation of the protein, mature GFPs are found in corals where
      hyperoxia and reactive oxygen species (ROS) occur due to the photosynthetic
      activity of algal symbionts. In vitro spin trapping electron paramagnetic
      resonance and spectrophotometric assays of superoxide dismutase (SOD)-like enzyme
      activity show that wild type GFP from the hydromedusa, Aequorea victoria,
      quenches superoxide radicals (O2*-)) and exhibits SOD-like activity by competing
      with cytochrome c for reaction with O2*-. When exposed to high amounts of O2*-
      the SOD-like activity and protein structure of GFP are altered without
      significant changes to the fluorescent properties of the protein. Because of the
      distribution of fluorescent proteins in both the epithelial and gastrodermal
      cells of reef-forming corals we propose that GFP, and possibly other fluorescent
      proteins, can provide supplementary antioxidant protection.

PMID- 17023115
TI  - Cytochrome P450--redox partner fusion enzymes.
AB  - The cytochromes P450 (P450s) are a broad class of heme b-containing mono
      oxygenase enzymes. The vast majority of P450s catalyse reductive scission of
      molecular oxygen using electrons usually derived from coenzymes (NADH and NADPH)
      and delivered from redox partner proteins. Evolutionary advantages may be gained
      by fusion of one or more redox partners to the P450 enzyme in terms of e.g.
      catalytic efficiency. This route was taken by the well characterized
      flavocytochrome P450(BM3) system (CYP102A1) from Bacillus megaterium, in which
      soluble P450 and cytochrome P450 reductase enzymes are covalently linked to
      produce a highly efficient electron transport system for oxygenation of fatty
      acids and related molecules. However, genome analysis and ongoing enzyme
      characterization has revealed that there are a number of other novel classes of
      P450-redox partner fusion enzymes distributed widely in prokaryotes and
      eukaryotes. This review examines our current state of knowledge of the diversity
      of these fusion proteins and explores their structural composition and
      evolutionary origins.

PMID- 17023117
TI  - Computerized lifelong mentoring support using robot for autistic individuals.
AB  - Developmental diversity in childhood is transformed into personality variation in
      adulthood. This view is now revalued through an ongoing paradigm shift in the
      field of developmental conditions, the transition from the qualitative dichotomy
      perspective to the quantitative concept. In the quantitative concept, autism is
      not a disease nor a developmental qualitative disorder, but a behavioral extreme
      in individual variation. Although the traditional qualitative view cannot
      interpret the recent worldwide prevalence of autism, the increase in the reported
      number of cases with autism and border cases can be easily explained by a
      dimensional exploration in which the primary autistic phenotype is regarded as an
      evolutional superiority. Therefore, the only suitable intervention is mentoring
      which provides a powerful lifelong support for higher social achievement in
      individuals with autism. Here, we hypothesize the coming mentoring circumstances
      for autistic individuals in the near future. Ongoing progress in robot and
      computer technology might allow the guardians to leave the major part of
      mentoring support to an individualized robot, and the 'folk physics' tendency in
      individuals with autism could facilitate the spread of the mentoring support
      system. The development of the robot mentor software may be simple because of the
      uniformity and stereotypy of the behavior patterns in individuals with autism.
      With the help of the robot mentor and under its guidance, autistic people might
      enjoy their social life and contribute to the prosperity of the human society to
      the maximum degree. Because the future population ratio of autistics/non
      autistics might be reversed according to the current trend of the prevalence,
      mentoring robot programs for autistic individuals should be developed without
      delay as a novel preliminary activity in the Jiminy Cricket movement, which is a
      campaign to reverse the estrangement of the present majority from autism and to
      increase the number of mentors for autistic individuals. In this article,
      prerequisites for the mentoring program of the robot mentor are expected and
      discussed.

PMID- 17023116
TI  - Purification, properties and cDNA cloning of neoverrucotoxin (neoVTX), a
      hemolytic lethal factor from the stonefish Synanceia verrucosa venom.
AB  - A proteinaceous toxin with hemolytic and lethal activities, named neoverrucotoxin
      (neoVTX), was purified from the venom fluid of stonefish Synanceia verrucosa and
      its primary structure was elucidated by a cDNA cloning technique. NeoVTX is a
      dimeric 166 kDa protein composed of alpha-subunit (702 amino acid residues) and
      beta-subunit (699 amino acid residues) and lacks carbohydrate moieties. Its
      hemolytic activity is inhibited by anionic lipids, especially potently by
      cardiolipin. These properties are comparable to those of stonustoxin (SNTX)
      previously purified from S. horrida. Alignment of the amino acid sequences also
      reveals that the neoVTX alpha- and beta-subunits share as high as 87 and 95%
      sequence identity with the SNTX alpha- and beta-subunits, respectively. The
      distinct differences between neoVTX and SNTX are recognized only in the numbers
      of Cys residues (18 for neoVTX and 15 for SNTX) and free thiol groups (10 for
      neoVTX and 5 for SNTX). In contrast, neoVTX considerably differs from
      verrucotoxin (VTX), a tetrameric 322 kDa glycoprotein, previously purified from
      S. verrucosa. In addition, the sequence identity of the neoVTX beta-subunit with
      the reported VTX beta-subunit is 90%, being lower than that with the SNTX beta
      subunit.

PMID- 17023118
TI  - Oral given Mepacrine could increase the resistance to heat environment injury.

PMID- 17023119
TI  - The role of triiodothyronine-induced substrate cycles in the hepatic response to
      overnutrition: thyroid hormone as an antioxidant.
AB  - Overnutrition, by generating reactive oxygen species (ROS), produces oxidative
      stress - an important cause of cellular injury. In the liver, overnutrition
      begins in the perivenous hepatocytes. To prevent injury, cells must protect
      themselves against ROS accumulation. Overnutrition also activates the enzyme
      deiodinase-1 (D1), which catalyzes the conversion of T4 to T3. D1 is primarily
      located in the PV region of the liver. Thyroid hormone is known to generate
      substrate cycling. The hypothesis of this paper is that a nutrient-induced
      increase in intracellular T3 acts as an antioxidant by inducing substrate cycles
      that reduce ROS accumulation. These cycles do this by: (i) reducing ROS formation
      by hydrolyzing excess ATP, thus enhancing oxidative phosphorylation and reducing
      the proton motive force on the electron transport chain (ETC), and; (ii)
      enhancing the removal (reduction) of ROS by producing the NADPH required for
      regeneration of reduced glutathione, a potent endogenous antioxidant. Oxidative
      stress is an important factor in the etiology of a number of hepatic injuries,
      including nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. In the
      latter, the frequency of mutations in thyroid hormone receptors (TRs) supports
      the concept that thyroid hormone acts as a tumor suppressor by reducing oxidative
      stress. This paper reviews the substrate cycles involved in this process. It also
      describes other mechanisms that permit rapid availability of T3 to cells
      undergoing oxidative stress.

PMID- 17023120
TI  - Pathogenesis of septal fibrosis of the liver. (An experimental study with a new
      model.).
AB  - Septal fibrosis is an important, frequent, and non-specific type of fibrosis
      associated with chronic liver diseases, but its pathogenesis is still poorly
      understood. An interesting model of septal fibrosis occurs in rats infected with
      the nematode Capillaria hepatica. This model was used to investigate the
      pathogenesis, site of origin, structure, and cell-types of septal fibrosis. Forty
      young adult Wistar rats were inoculated with 800 embryonated eggs of C. hepatica.
      Daily liver samples were obtained from the 20th to the 39th day after inoculation
      to cover the critical period when septal fibrosis usually starts. Routine
      histology, electron microscopy, immunohistochemistry, and indirect
      immunofluorescence were applied to the study of liver sections. Septal blood
      vessels were demonstrated by India ink perfusion of the portal vein system.
      Prominent angiogenesis was observed to precede collagen deposition. Besides
      angiogenesis and mesenchymal-cell mobilization, septal fibrosis was seen to
      originate from portal spaces and to course through acinar zone I in between
      sinusoids, inducing no alterations in them, with no evident participation of
      stellate hepatic cells. Septal fibrosis appeared as an adaptative type of
      response of the liver to chronic injury, which resulted in a new structure that
      is normal to other species and creates accessory vessels that drain portal blood
      into hepatic sinusoids.

PMID- 17023121
TI  - [Towards new antibacterial drugs. Interest of para-guanidinoethylcalix[4]arene].
AB  - We present here the results concerning the antibacterial properties evaluation of
      para-guanidinoethylcalix[4]arene, compared with its constitutive monomer, the
      para-guanidinoethylphenol, and hexamidine (Hexomedine), an antiseptic from the
      diamidine family widely used in therapeutic, chosen as a reference in this study
      for its resemblance in terms of functional groups. Antibacterial activities of
      those three compounds were evaluated by microdilution methods, in Mueller Hinton
      broth, onto 5 bacterial strains: Escherichia coli ATCC 25922, Pseudomonas
      aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 & ATCC 29213 and
      Enterococcus faecalis ATCC 29212, according to CA-SFM and CLSI (formerly NCCLS)
      approved standards. In parallel, the effects of these three compounds on MRC-5
      eukaryotic cell viability were evaluated with MTT assay. The results obtained
      here confirm a lack of activity for the monomer compound (MIC> or =512 mg/l) and
      a real antibacterial activity for the calixarene, comparable to hexamidine. This
      activity is expressed, both on Gram+and Gram- bacteria (MIC=4 mg/l for E. coli, 8
      mg/l on both S. aureus strains) and at a lesser degree on E. faecalis and P.
      aeruginosa (MIC=32 mg/l). Similarly, both compounds, monomer and calixarene,
      slightly induce any modification on MRC-5 cells viability, and this until 168 h
      of treatment for concentrations reaching 10(-4) mol/L while hexamidine
      demonstrates a significant and increasing effect during the time of experiment
      and this for 100 to 1000 times lower concentrations. Thus, this study tends to
      confirm the significance of the organization of the para-guanidinoethylphenol
      monomer into its cyclic calixarenic tetramer for the gain of an antibacterial
      activity, similar to a widely used antiseptic one.

PMID- 17023122
TI  - Impulsive responding on the peak-interval procedure.
AB  - The pattern of responding on a peak-interval timing task allows one to make
      inferences regarding the sources of variation that contribute to interval timing
      behavior. Non-temporal factors such as impulsivity may impact the validity of
      these inferences. Rats were trained on a 15s peak-interval procedure (PI) or a
      mixed 15s behaviorally dependent variable-interval, 15s peak-interval procedure
      (bdVIPI) for an extended number of sessions. Extended training on the PI revealed
      a bi-modal distribution in the times at which subjects started responding for
      temporally predictable reinforcement, suggesting that multiple processes
      contribute to the behavioral pattern obtained in this procedure. Training on the
      bdVIPI eliminated the early mode of this bi-modal distribution, thereby
      decreasing the variation in start times. These results suggest that alternative
      response options can modulate the influence of impulsivity in timing tasks.

PMID- 17023124
TI  - Requirements for polyadenylation at the 3' end of LINE-1 elements.
AB  - LINE-1 (L1) is the only active, autonomous, non-LTR, human retroelement. There
      are about 5x10(5) L1 copies in the human genome, the majority of which are
      truncated at their 5' ends. Both truncated and full-length L1 insertions contain
      a polyadenylation (polyA) signal at their 3' ends. A typical polyA site consists
      of the three main cis-acting elements: a conserved hexamer, cleavage site, and a
      GU-rich downstream region. A newly inserted L1 copy contains the conserved AATAAA
      hexamer at the end of its sequence. However, the GU-rich downstream region has to
      be provided by the neighboring genomic sequences and therefore it would vary for
      every L1 copy. Using northern blot analysis of transiently transfected L1
      expression vectors we demonstrate that L1 element contain sequence that allow
      efficient polyadenylation at the L1 3' end upon retrotransposition into a new
      genomic location independent of the base composition downstream of the insertion
      site. The strategy of polyadenylation at the 3' end of L1 parallels the approach
      the element employs at its 5'UTR by having an unusual internal polymerase II
      promoter, making new insertions less dependent on the properties of the flanking
      sequences at the new locus.

PMID- 17023123
TI  - Training and fidelity monitoring of behavioral interventions in multi-site
      addictions research.
AB  - AIMS: Methods for the training and fidelity monitoring of behavioral
      interventions in multi-site addictions research are reviewed, including five
      published studies and seven ongoing studies sponsored by the National Institute
      on Drug Abuse-funded Clinical Trials Network. METHODS: Methods are categorized
      and reviewed consistent with a technology model of treatment delivery. Topics
      include: therapist selection, training, certification, and supervision;
      selection, training, and certification of supervisors; scales and processes used
      for monitoring of the quality of treatment; and processes followed to provide new
      training for replacement staff once trials have begun. RESULTS: The review
      reveals both a wide array of procedures and emerging standards for multi-site
      trials. Methodological weakness was observed with respect to limited empirical
      support for many adherence scales, little or no evaluation of supervisory
      processes, and no evaluation of re-training practices. CONCLUSIONS: Methods used
      in multi-site trials are important not only to ensure validity of those trials,
      but also to inform the wider dissemination of empirically based treatment into
      community agencies. Studies examining noted weaknesses are needed. Training and
      fidelity models that delegate responsibility to participating sites appear most
      relevant for establishing best practices for dissemination of behavioral
      interventions. The effectiveness of these distributed training and supervision
      models should be subjected to empirical study at a level of rigor comparable to
      the evaluation of their corresponding treatments.

PMID- 17023125
TI  - Pouch young removal and return to oestrus in wild southern hairy-nosed wombats
      (Lasiorhinus latifrons).
AB  - The southern hairy-nosed wombat (Lasiorhinus latifrons) is a seasonal breeding,
      burrowing marsupial adapted to a semi-arid environment and the closest relative
      of the endangered northern hairy-nosed wombat (Lasiorhinus krefftii). Females
      typically give birth to one to two young every 3 years with young weaned at 360
      400 days. This study examined the occurrence of polyoestry in a wild population
      of southern hairy-nosed wombats, and in particular the ability of this species to
      produce additional offspring in the same breeding season if a young was
      prematurely lost or removed. Pouch young were removed during the breeding seasons
      of 1996/1997 and 2003. No females from the 1996 (n=3)/1997 (n=3) group gave birth
      to a second pouch young in the same breeding season. However, two females in this
      group gave birth to young the following season. In contrast, all the 2003 group
      of females (n=6) produced a second offspring in the same breeding season after
      removal of pouch young (RPY). The reason for the different response to RPY
      between the two groups is unknown. These studies confirm that southern hairy
      nosed wombats are polyoestrus in the wild and are capable of producing more than
      one offspring in a single breeding season. Females that failed to return to
      oestrus in the breeding season that pouch young were removed bred again in the
      following season. Rapid replacement of southern hairy-nosed wombat pouch young in
      the same breeding season as RPY suggests that this procedure, linked to either
      hand-rearing or interspecific cross-fostering, should be seriously considered as
      a priority conservation action to increase the population size of the critically
      endangered sister species, the northern hairy-nosed wombat.

PMID- 17023127
TI  - Characterisation and physical stability of PEGylated glucagon.
AB  - Glucagon was mono-PEGylated with PEG 5000 at Lys-12 to examine the effect on
      conformation and physical stability during purification and freeze-drying. The
      model peptide glucagon is highly unstable and readily forms fibrils in solution.
      Secondary structure was determined by FTIR and far-UV CD and physical stability
      was assessed by the Thioflavin T assay. Glucagon samples were included, which
      underwent the same RP-HPLC purification and/or freeze-drying as glucagon-PEG
      5000. After purification and freeze-drying glucagon samples showed formation of
      intermolecular beta-sheet by FTIR, this correlated with shorter lag-times for
      fibrillation in the Thioflavin T assay. Formation of intermolecular beta-sheet
      was less apparent for glucagon-PEG 5000 and no fibrillation was detected by
      Thioflavin T assay. Apparently PEGylation significantly improved the physical
      stability of glucagon after purification and freeze-drying, possibly by steric
      hindrance of peptide-peptide interactions. Alterations in the secondary structure
      were observed for freeze-dried and reconstituted peptide samples by liquid FTIR.
      The peak for alpha-helix shifted to 1664 cm(-1), which could possibly be
      explained by formation of 3(10)-helix. Neither 3(10)-helix nor intermolecular
      beta-sheet could be detected by far-UV CD, where all peptide samples showed
      similar spectra. In conclusion, glucagon-PEG 5000 showed a significantly improved
      physical stability during purification and freeze-drying compared to glucagon.

PMID- 17023126
TI  - Expression of proopiomelanocortin, proenkephalin and prodynorphin genes in
      porcine theca and granulosa cells.
AB  - Previous studies have demonstrated the presence of endogenous opioid peptides
      (EOP) in the ovary and suggested their implication in local interactions within
      ovarian structures. Nevertheless, data pertaining to the expression of genes,
      coding for the opioid precursors, in ovarian cells are still rudimentary and not
      available for the pig. The study was undertaken to test whether genes of the
      opioid precursors - proopiomelanocortin (POMC), proenkephalin (PENK) and
      prodynorphin (PDYN) - are expressed in non-treated and gonadotropin-treated theca
      and granulosa cells isolated from ovarian follicles of the pig. The cells were
      isolated from small (days 15-16 of the estrous cycle) and large (days 19-20)
      porcine follicles. Dispersed cells were cultured in Eagle's medium under the
      water saturated atmosphere of 95% air and 5% CO(2), in the presence or absence of
      respective gonadotropin; theca cells with LH (100 ng/ml) and granulosa cells with
      FSH (100 ng/ml). Following 24h-incubation, the cells were harvested and the total
      RNA was isolated. The expression of genes coding for opioid precursors was
      estimated by the semi-quantitative RT-PCR technique involving co-amplification of
      the target cDNA (POMC, PENK or PDYN) and control cDNA (beta-actin or 18S rRNA).
      Specificities of PCR products were confirmed by Southern analysis and sequencing.
      In theca cells the expression of opioid precursors appeared to be gonadotropin
      dependent except for PENK in the cells isolated from large follicles. In turn,
      granulosa cells exhibited the expression of POMC and PENK genes independently on
      treatment with FSH. This gonadotropin induced the expression of PDYN gene in
      granulosa cells isolated from small and large follicles and significantly
      increased POMC mRNA content in the cells from the large ones. The present studies
      indicate that porcine follicular cells (especially granulosa cells) may produce
      opioid peptides and that gonadotropins may modulate gene expression of their
      precursors in these cells. Moreover, our results support a participation of
      opioid peptides in the local regulations within ovarian follicle.

PMID- 17023128
TI  - Afferent synapses are present in utricular hair cells from otoconia-deficient
      mice.
AB  - The head tilt mouse (het/het, abbr. het) is a naturally occurring mutant whose
      salient phenotypic traits include the complete absence of otoconia in both the
      utricle and saccule. Cursory histologic evaluation has indicated that the
      neuroepithelia exhibit a normal appearance. Though evidence exists indicating
      that utricular function is severely if not completely compromised in these
      animals, it is not yet known whether afferent synapses exist within utricular
      hair cells of otoconia-deficient mutants. The absence of synapses would be
      suggestive of a trophic relationship between stimulus-evoked hair cell activation
      and the afferent synapse. To address this question, we have conducted an
      ultrastructural survey of utricular sensory epithelia from confirmed het mice.
      The specific objective was to determine whether utricular hair cells made
      synaptic contact with afferent neurons. We found that both type I and II hair
      cells from utricles of het mice exhibited afferent synapses that were found at
      numerous sites distributed throughout the utricle. These results indicate that
      afferent synapses within vestibular hair cells do not critically depend upon
      stimulus-evoked activity.

PMID- 17023129
TI  - Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and
      acetyl-L-carnitine.
AB  - Despite the use of hearing protection devices (HPDs) and engineering changes
      designed to improve workspaces, noise-induced hearing loss continues to be one of
      the most common and expensive disabilities in the US military. Many service
      members suffer acoustic trauma due to improper use of HPDs, sound levels
      exceeding the protective capacity of the HPDs, or by unexpected, injurious
      exposures. In these cases, there is no definitive treatment for the hearing loss.
      This study investigated the use of the pharmacological agents N-acetylcysteine
      and acetyl-L-carnitine after acoustic trauma to treat cochlear injury. N
      Acetylcysteine is an antioxidant and acetyl-L-carnitine a compound that maintains
      mitochondrial bio-energy and integrity. N-Acetylcysteine and acetyl-L-carnitine,
      respectively, significantly reduced permanent threshold shifts and hair cell loss
      compared to saline-treated animals when given 1 and 4 h post-noise exposure. It
      may be possible to obtain a greater therapeutic effect using these agents in
      combination or at higher doses or for a longer period of time to address the
      secondary oxidative events occurring 7-10 days after acute noise exposure.

PMID- 17023130
TI  - Further studies on the antinociceptive action of aqueous seed extract of
      Aframomum melegueta.
AB  - This study presents the results of further investigations on the antinociceptive
      profiles of an aqueous seed extract of Aframomum melegueta in rodents. The
      antinociceptive activity of the intraperitonal doses of 25-100 mg/kg of Aframomum
      melegueta was assessed using the formalin-induced paw licking, Randall-Selitto
      paw pressure and hot plate models of pain. The extract was found to produce a
      significant dose-dependent inhibition of the inflammatory but not the neurogenic
      pains associated with the formalin test. In the Randall-Sellito paw pressure
      test, the extract significantly reduced the nociceptive responses elicited by
      compression of inflamed hind paw of rats in a dose-related manner. However,
      Aframomum melegueta did not alter the pain threshold in non-inflamed paw and also
      failed to prolong the reaction time of the animals to noxious heat in the hot
      plate test. Taken together, these findings suggest that the aqueous seed extract
      of Aframomum melegueta possess peripheral analgesic activity.

PMID- 17023131
TI  - Tabernaemontana divaricata extract inhibits neuronal acetylcholinesterase
      activity in rats.
AB  - The current pharmacotherapy for Alzheimer's disease (AD) is the use of
      acetylcholinesterase inhibitors (AChE-Is). A previous in vitro study showed that
      Tabernaemontana divaricata extract (TDE) can inhibit AChE activity. However,
      neither the AChE inhibitory effects nor the effect on neuronal activity of TDE
      has been investigated in vivo. To determine those effects of TDE in animal
      models, the Ellman's colorimetric method was implemented to investigate the
      cortical and circulating cholinesterase (ChE) activity, and Fos expression was
      used to determine the neuronal activity in the cerebral cortex, following acute
      administration of TDE with various doses (250, 500 and 1000 mg/kg) and at
      different time points. All doses of TDE 2 h after a single administration
      significantly inhibited cortical AChE activity and enhanced neuronal activity in
      the cerebral cortex. The enhancement of Fos expression and AChE inhibitory
      effects in the cerebral cortex among the three TDE-treated groups was not
      significantly different. A 2 h interval following all doses of TDE administration
      had no effect on circulating ChE activity. However, TDE significantly inhibited
      circulating AChE 10, 30 and 60 min after administration. Our findings suggest
      that TDE is a reversible AChE-I and could be beneficial as a novel therapeutic
      agent for AD.

PMID- 17023132
TI  - Promnesic effects of Ptychopetalum olacoides in aversive and non-aversive
      learning paradigms.
AB  - Homemade remedies with Ptychopetalum olacoides (PO) roots are used by Amazonian
      peoples for treating various age-related conditions. We previously reported that
      Ptychopetalum olacoides ethanol extract significantly improved step-down
      inhibitory avoidance long-term memory in adult and reversed memory deficits in
      aging mice. Adding to previous data, this study shows that a single i.p.
      administration of Ptychopetalum olacoides ethanol extract (POEE 50 and 100 mg/kg)
      improved step-down inhibitory avoidance short-term memory (STM) 3 h after
      training in adult (2.5 month) mice; comparable results were obtained with POEE
      given p.o. at 800 mg/kg. Moreover, memory improvement was also observed in aging
      (14 months) mice presenting memory deficit as compared to adult mice.
      Furthermore, POEE (100 mg/kg) improved non-aversive memory systems in adult mice
      in an object recognition paradigm. Consistently with its traditional use this
      study add to previously reported data and reinforces that POEE facilitates memory
      processes. Although the acetylcholinesterase inhibitory properties described for
      this extract may be of relevance for improving memory processes, the molecular
      mechanism(s) underlying the memory improvement here reported needs further
      scrutiny.

PMID- 17023133
TI  - Prevalence of diatom frustules in non-vegetarian foodstuffs and its implications
      in interpreting identification of diatom frustules in drowning cases.
AB  - Detection of diatom frustules in bone marrow (diatom test) is used for diagnosing
      ante-mortem drowning where the usual signs of drowning are not present in dead
      bodies recovered from water. However, controversies over the reliability of
      diatom test results are continuing. There have been indications on the
      possibilities of diatoms entering into systemic circulation from atmospheric air,
      food and drink. While diatoms have been demonstrated in the gut content of edible
      marine forms such as shrimps and clams, the present study, for the first time,
      provides empirical evidence on the prevalence as well as abundance of diatom
      frustules in the samples of cooked non-vegetarian foodstuffs that impend human
      consumption in Kelantan, Malaysia. It is found that 50 g each of cleaned and
      cooked prawns and of clams impending human consumption contain about 8360 and
      29,054 diatom frustules, respectively. A person accustomed to prawn and clam food
      would be ingesting an estimated 2 million diatoms in a single year. Considering
      the suggestion that detection of five diatom frustules in 10 g of bone marrow
      would suffice for concluding drowning as mode of death, and the fact that there
      is yet no proof that diatom frustules do not enter into the human systemic
      circulation through the digestive tract, the estimated number of diatom frustules
      routinely ingested acquires significance since entry of a few of such ingested
      frustules into the systemic circulation can lead to false positive test results.
      The findings of this research raise two important issues: first, population based
      routine food related diatom ingestion requires to be estimated, and, second,
      studies have to be initiated to categorically prove or disprove the possibility
      of entry of diatom frustules into the systemic circulation via the digestive
      tract.

PMID- 17023134
TI  - Latent fingermark visualisation using a scanning Kelvin probe.
AB  - The current state of the art in fingermark visualisation on metallic surfaces by
      a scanning Kelvin probe (SKP) technique is described. Latent eccrine fingermarks
      deposited on a range of polished and roughened metallic surfaces can be
      effectively imaged. Results are presented which show that the SKP technique is
      able to visualise fingermarks obscured beneath optically opaque soot films and
      retrieve ridge detail in instances where fingermarks have been physically removed
      (e.g. by rubbing with a tissue) from a metal surface. SKP Volta potential mapping
      of small, severely non-planar metal objects such as fired brass cartridge cases
      is demonstrated.

PMID- 17023135
TI  - MR flow measurements for assessment of the pulmonary, systemic and
      bronchosystemic circulation: impact of different ECG gating methods and breathing
      schema.
AB  - PURPOSE: Different ECG gating techniques are available for MR phase-contrast (PC)
      flow measurements. Until now no study has reported the impact of different ECG
      gating techniques on quantitative flow parameters. The goal was to evaluate the
      impact of the gating method and the breathing schema on the pulmonary, systemic
      and bronchosystemic circulation. MATERIAL AND METHODS: Twenty volunteers were
      examined (1.5 T) with free breathing phase-contrast flow (PC-flow) measurements
      with prospective (free-prospective) and retrospective (free-retrospective) ECG
      gating. Additionally, expiratory breath-hold retrospective ECG gated measurements
      (bh-retrospective) were performed. Blood flow per minute; peak velocity and time
      to peak velocity were compared. The clinically important difference between the
      systemic and pulmonary circulation (bronchosystemic shunt) was calculated.
      RESULTS: Blood flow per minute was lowest for free-prospective (6 l/min,
      pulmonary trunc) and highest for bh-retrospective measurements (6.9 l/min,
      pulmonary trunc). No clinically significant difference in peak velocity was
      assessed (82-83 cm/s pulmonary trunc, 109-113 cm/s aorta). Time to peak velocity
      was shorter for retro-gated free-retrospective and bh-retrospective than for pro
      gated free-prospective. The difference between systemic and pulmonary
      measurements was least for the free-retrospective technique. CONCLUSION: The type
      of gating has a significant impact on flow measurements. Therefore, it is
      important to use the same ECG gating method, especially for follow-up
      examinations. Retrospective ECG gated free breathing measurements allow for the
      most precise assessment of the bronchosystemic blood flow and should be used in
      clinical routine.

PMID- 17023136
TI  - Method development and validation for the simultaneous determination of
      cetirizine dihydrochloride, paracetamol, and phenylpropanolamine hydrochloride in
      tablets by capillary zone electrophoresis.
AB  - A simple, selective, and cost effective capillary zone electrophoresis (CZE)
      method has been developed for the simultaneous separation and determination of
      cetirizine dihydrochloride (CTZ), paracetamol (PARA), and phenylpropanolamine
      hydrochloride (PPA) in tablets. A 10 mM sodium tetraborate background electrolyte
      (BGE) solution (pH 9.0) was found to be suitable for separation of all the
      analytes. An uncoated fused-silica capillary of a total length of 76 cm
      (effective length 64.5 cm) was used for separation. All the analytes were
      completely separated within 10 min at the applied voltage of 20 kV (current
      produced approximately 21 microA), and detection was performed at 195 nm with an
      UV detector. Ibuprofen was used as internal standard (I.S.) for the
      quantification of the drugs. Validation of the method was performed in terms of
      linearity, accuracy, precision, limit of detection (LOD), and quantification
      (LOQ). The linearity of the calibration curves for CTZ, PARA, and PPA (tested
      range) were 2-50 microg ml(-1) (r(2)=0.9982), 10-1000 microg ml(-1)
      (r(2)=0.9978), and 10-100 microg ml(-1) (r(2)=0.9986), respectively. The proposed
      method has been applied for the determination of active ingredients in tablets,
      and the recovery was found to be > or =98.60% with the relative standard
      deviation (R.S.D.) < or =1.56%. The LOQ of the CTZ, PARA, and PPA was found to be
      2.0, 2.0, and 4.0 microg ml(-1), respectively. There were no interfering peaks
      due to the excipients present in the pharmaceutical tablets. Thus, the proposed
      method is simple and suitable for the simultaneous analysis of active ingredients
      in tablet dosage forms.

PMID- 17023137
TI  - Study of the physicochemical properties in aqueous medium and molecular modeling
      of tagitinin C/cyclodextrin complexes.
AB  - The inclusion complexes of tagitinin C with beta-, 2,6-di-O-methyl-beta- and
      gamma-cyclodextrin (CyD) was investigated in aqueous medium. The stoichiometric
      ratios and stability constants (K(f)) which describe the extent of formation of
      the complexes have been determined by UV spectroscopy and direct current tast
      polarography (DC(tast)), respectively. For each complex, a 1:1 molar ratio was
      formed in solution and the trend of stability constants was K(f) (2,6-di-O-methyl
      beta-CyD)>K(f) (gamma-CyD)>K(f) (beta-CyD). The effect of molecular encapsulation
      on the photochemical conversion of tagitinin C was evaluated. No significant
      protection efficacy was noticed with beta- and gamma-CyD for the complexed drug
      with the respect to the free one. On the other hand, the photochemical conversion
      rate was slowed in presence of 2,6-di-O-methyl-beta-CyD. Data from (1)H NMR and
      ROESY experiments provided a clear evidence of formation of inclusion complexes.
      The lactone, the ester and the unsaturated ketone parts of tagitinin C inserted
      into the wide rim of the CyDs torus. These experimental results were confirmed by
      the molecular modeling using semiempirical Austin Model 1 (AM1) method.

PMID- 17023138
TI  - An approach to measuring the quality of breast cancer decisions.
AB  - OBJECTIVE: To explore an approach to measuring the quality of decisions made in
      the treatment of early stage breast cancer, focusing on patients' decision
      specific knowledge and the concordance between patients' stated preferences for
      treatment outcomes and treatment received. METHODS: Candidate knowledge and value
      items were identified after an extensive review of the published literature as
      well as reports on 27 focus groups and 46 individual interviews with breast
      cancer survivors. Items were subjected to cognitive interviews with six
      additional patients. A preliminary decision quality measure consisting of five
      knowledge items and four value items was pilot tested with 35 breast cancer
      survivors who also completed the control preferences scale and the decisional
      conflict scale (DCS). RESULTS: Preference for control and knowledge did not vary
      by treatment. The mean of the participants' knowledge scores was 54%. There was
      no correlation between the knowledge scores and the informed subscale of the DCS
      (Pearson r = .152, n = 32, p = 0.408). Patients who preferred to keep their
      breast were over five times as likely to have breast-conserving surgery than
      those who did not (OR 5.33, 95% CI (1.2, 24.5), p = 0.06). Patients who wanted to
      avoid radiation were six times as likely to choose mastectomy than those who did
      not (OR 6.4, 95% CI (1.34, 30.61), p = 0.04). CONCLUSION: Measuring decision
      quality by assessing patients' decision-specific knowledge and concordance
      between their values and treatment received, is feasible and important. Further
      work is necessary to overcome the methodological challenges identified in this
      pilot work. PRACTICE IMPLICATIONS: Guidelines for early stage breast cancer
      emphasize the importance of including patients' preferences in decisions about
      treatment. The ability of doctors and patients to make decisions that reflect the
      considered preferences of well-informed patients can and should be measured.

PMID- 17023139
TI  - [Perineal regional anaesthesia: indications in gynaecologic and proctologic
      surgery and in obstetric].
AB  - Perineal and proctologic surgery is well known as very painful. The apparition of
      new specific needles, long acting and less toxic local anaesthetics and
      neurostimulation allowed reconsidering some old forgotten techniques. Those
      blocks appear really useful to optimize multimodal postoperative analgesia and
      postoperative rehabilitation. After anatomic review, authors describe perineal
      regional anaesthesia and discuss about main indications and advantages, in the
      eyes of their experience and bibliographic review.

PMID- 17023140
TI  - Potential for interpretation disparities of Halstead-Reitan neuropsychological
      battery performances in a litigating sample.
AB  - The performances of 110 litigants on seven variables from the Halstead-Reitan
      neuropsychological battery (HRNB) were used to compare Heaton, Miller, Taylor,
      and Grant's (2004) Deficit Scale (DS) and Reitan and Wolfson's (1993)
      Neuropsychological Deficit Scale (NDS). Additional comparisons were made for
      people who passed or failed the Test of Memory Malingering (TOMM) to determine
      effects of effort on scores generated by either scoring system. Wilcoxon signed
      rank tests revealed that all seven comparisons were significantly different for
      the full sample (p< or =0.001). The NDS indicated greater levels of impairment
      compared to DS across all variables. These findings were also obtained when
      considering effort, though TOMM failure was related to non-significant
      differences for two variables. These findings suggest that the two scoring
      systems are not equivalent, with Heaton et al.'s DS resulting in consistently
      higher identification rates of normal brain functioning compared to those
      generated from Reitan and Wolfson's NDS system.

PMID- 17023141
TI  - Induction of apoptosis by 25-hydroxycholesterol in adult rat Leydig cells:
      protective effect of 17beta-estradiol.
AB  - Testicular macrophages can convert cholesterol into 25-hydroxycholesterol which
      strongly stimulates Leydig cell testosterone production. We demonstrated that 25
      hydroxycholesterol reduced cholesterol biosynthesis in adult rat Leydig cells.
      This oxysterol can also be cytotoxic. As hydroxylated cholesterol can induce
      apoptosis in various cells, we investigated cell death produced by 25
      hydroxycholesterol. Apoptosis was characterized by TUNEL assay and by DAPI test.
      Addition of 25-hydroxycholesterol, during 24h, induced a dose dependent increase
      of apoptosis. This effect was reduced by a treatment with a caspase-3 inhibitor
      (Ac-DEVD-CHO). 25-Hydroxycholesterol is known to stimulate testosterone
      production, but an increase of intracellular or culture medium testosterone level
      does not modify significantly the percentage of apoptotic cells. In contrast,
      addition of 17beta-estradiol (2 nM) induced a decrease of apoptotic cells. These
      data suggested that this oxysterol can be used by rat Leydig cells in culture for
      sterol metabolism, but also induces apoptosis which could be inhibited by 17beta
      estradiol.

PMID- 17023142
TI  - Dual kinase-mediated regulation of PITK by CaMKII and GSK3.
AB  - Phosphatase Interactor Targeting K protein (PITK) was previously identified as a
      novel PP1 targeting subunit implicated in modulating the phosphorylation of the
      transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K)
      [Kwiek NC, Thacker DF, Datto MB, Megosh HB, Haystead TA. Cell Signal 18 (10)
      (2006) 1769.]. Through the phosphorylation of PITK at S1013 and S1017 (residues
      that flank or reside within a PP1C-binding motif), the binding of the PP1
      catalytic subunit to PITK, and subsequently the activity of the holoenzyme, are
      discretely controlled. Herein, we demonstrate that PITK phosphorylation at S1013
      and S1017 also dictates the subcellular localization of the holoenzyme. Whereas
      both wildtype-and an S1013,1017D-PITK mutant displayed a speckled nuclear
      localization, a constitutively dephosphorylated form of PITK (S1013,1017A-PITK)
      resulted in a diffuse localization throughout the cell including the cytoplasm.
      Additionally, through the use of unbiased proteomics techniques, we provide
      evidence for a dual kinase-mediated regulation of the PITK holoenzyme whereby
      PITK phosphorylation at S1017 is catalyzed by calcium/calmodulin-dependent kinase
      II-delta (CaMKIIdelta), promoting the subsequent phosphorylation of S1013 by
      glycogen synthase kinase-3 (GSK3) in vitro. Taken together, our findings provide
      further insight into the regulation of PITK, PP1, and hnRNP K by reversible
      phosphorylation.

PMID- 17023143
TI  - Cervical infection with descending mediastinitis: a review of six cases.
AB  - The aim of this study was to retrospectively review cases of cervical infection
      with descending mediastinitis, and to analyse the clinical character, diagnosis
      and treatment of this infection. Six patients were identified from December 1998
      to June 2005. Their aetiology, associated systemic diseases, bacteriology,
      radiology, treatments and outcomes were reviewed. Four cases resulted from
      odontogenic infection, one from upper airway infection, and one had an unknown
      cause. Diffuse swelling in face and neck, chest distress, tachypnea, and fever
      were the main symptoms. Chest radiography showed a widening of the upper
      mediastinal shadow in four patients. Four patients underwent computed tomographic
      scanning that confirmed the diagnosis of descending mediastinitis, which suggests
      that routine use of this scan be highly recommended for early detection. Six
      different pathogens were identified through pus and blood culture. All patients
      underwent surgical drainage. Three patients received a tracheotomy. Of the six
      patients, four achieved good results, and there were two deaths. Early surgical
      drainage remains the main treatment for cervical infection with descending
      mediastinitis. Delayed diagnosis, inadequate drainage and multidrug-resistant
      bacterial infection were responsible for the deaths.

PMID- 17023144
TI  - The use of tissue-engineered bone with human bone morphogenetic protein-4
      modified bone-marrow stromal cells in repairing mandibular defects in rabbits.
AB  - In this study, the capacity of hBMP-4 gene therapy combined with tissue
      engineering techniques to improve the repair of mandibular osseous defects in
      rabbits was explored. A mammalian plasmid vector expressing enhanced green
      fluorescent protein-human bone morphogenetic protein-4 (pEGFP-hBMP-4) was
      initially constructed through subcloning techniques. Bone-marrow stromal cells
      (bMSCs) from New Zealand White rabbits were cultured and either transfected with
      pEGFP-hBMP-4 or pEGFP, or left untransfected in vitro. Once the transfer
      efficiency was determined through the expression of EGFP, cells from the three
      groups were combined with natural non-organic bone (NNB) at a concentration of 50
      x 10(6)cells/ml and placed in 15 mm x 6 mm bilateral, full-thickness, mandibular
      defects surgically made in 12 rabbits. Together with NNB control, there were six
      samples per group. Four weeks after surgery, the implants were harvested and
      evaluated histomorphologically. Under optimal experimental conditions, gene
      transfer efficiency reached a maximum of 38.2+/-9.4%. While the percentage of new
      bone area in the NNB control group was 8.8+/-3.1%, in the untransfected bMSC
      group 22.5+/-8.2%, and in the pEGFP group 18.1+/-9.0%, a significantly higher
      amount of 32.5+/-6.1% was observed in the pEGFP-hBMP-4 group. These results
      suggest that transfection of bMSCs with hBMP-4 enhances their inherent osteogenic
      capacity for maxillofacial bone tissue-engineering applications.

PMID- 17023145
TI  - Successful multi-site measurement of antisaccade performance deficits in
      schizophrenia.
AB  - The antisaccade task is a promising schizophrenia endophenotype; it is stable
      over time and reflects neurophysiological deficits present in both schizophrenia
      subjects and their first-degree relatives. Meaningful genetic research requires
      large sample sizes that are best ascertained using multi-site study designs. To
      establish the criterion validity of the antisaccade task in a multi-site design,
      the Consortium on the Genetics of Schizophrenia (COGS) examined whether seven
      sites could detect previously reported antisaccade deficits in schizophrenia
      subjects. Investigators presented 3 blocks of 20 antisaccade stimuli to 143
      schizophrenia subjects and 195 comparison subjects. Frequent collaborator
      communication, standardized training, and ongoing quality assurance optimized
      testing uniformity. Data were discarded from only 1.2% of subjects due to poor
      quality, reflecting the high fidelity of data collection and scoring methods. All
      sites detected a significant difference in the proportion of correct antisaccades
      between schizophrenia and comparison subjects (p<.02 at all sites); group
      differences in gain and latency were less robust. Regression analyses to adjust
      for the effects of group, site, age, gender, smoking, and parental education on
      the proportion of correct antisaccades revealed a significant effect of group,
      site, and age but no effect of gender, smoking, or parental education, and no
      group-by-site interactions. Intraclass correlations between proportion of correct
      antisaccades across the blocks of stimuli ranged from 0.87 to 0.93, demonstrating
      good within-session reliability at sites. These results confirm previous findings
      of antisaccade deficits in schizophrenia subjects and support the use of the
      antisaccade task as a potential schizophrenia endophenotype in multi-site genetic
      studies.

PMID- 17023147
TI  - Vanadium-51 solid-state NMR electric field gradient tensors: a DFT-embedded ion
      and isolated cluster study of crystalline vanadium oxides.
AB  - Density functional theory (DFT) calculations (6-311+G(2d,p)/B3LYP level of
      theory) of (51)V electric field gradient (EFG) tensor elements are performed for
      embedded and isolated cluster models of orthovanadates. The structural models
      used to calculate the EFGs of (51)V are (I) an isolated H(4)VO(4)(+) cluster,
      (II) an isolated H(n)VO(4)(n-3) cluster (n=number of next-neighbor cations) (III)
      an isolated orthovanadate anion, VO(4)(-x), and (IV) a VO(4)(-x) ion embedded in
      a finite point-charge array whose electrostatic potential, at the embedded ion,
      is equivalent to that of the infinite lattice. For models III and IV, a charge x
      is assigned estimating the covalence of the system. Models III and IV provide
      results in good agreement with the experiment. Calculations, employing the
      embedded and isolated VO(4)(-x) models, are used to discuss site assignments for
      AlVO(4). Correlations between quadrupole coupling parameters and deviations of
      the orthovanadate structure from ideal tetrahedral symmetry are shown.

PMID- 17023146
TI  - Progress towards understanding disease mechanisms in small vertebrate models of
      neuronal ceroid lipofuscinosis.
AB  - Model systems provide an invaluable tool for investigating the molecular
      mechanisms underlying the NCLs, devastating neurodegenerative disorders that
      affect the relatively inaccessible tissues of the central nervous system. These
      models have enabled the assessment of behavioural, pathological, cellular, and
      molecular abnormalities, and also allow for development and evaluation of novel
      therapies. This review highlights the relative advantages of the two available
      small vertebrate species, the mouse and zebrafish, in modelling NCL disease,
      summarising how these have been useful in NCL research and their potential for
      the development and testing of prospective disease treatments. A panel of mouse
      mutants is available representing all the cloned NCL gene disorders (Cathepsin D,
      CLN1, CLN2, CLN3, CLN5, CLN6, CLN8). These NCL mice all have progressive
      neurodegenerative phenotypes that closely resemble the pathology of human NCL.
      The analysis of these models has highlighted several novel aspects underlying NCL
      pathogenesis including the selective nature of neurodegeneration, evidence for
      glial responses that precede neuronal loss and identification of the thalamus as
      an important pathological target early in disease progression. Studies in mice
      have also highlighted an unexpected heterogeneity underlying NCL phenotypes, and
      novel potential NCL-like mouse models have been described including mice with
      mutations in cathepsins, CLC chloride channels, and other lysosome-related genes.
      These new models are likely to provide significant new information on the
      spectrum of NCL disease. Information on NCL mice is available in the NCL Mouse
      Model Database (). There are homologs of most of the NCL genes in zebrafish, and
      NCL zebrafish models are currently in development. This model system provides
      additional advantages to those provided by NCL mouse models including high
      throughput mutational, pharmacogenetic and therapeutic technique analyses. Mouse
      and zebrafish models are an important shared resource for NCL research, offering
      a unique possibility to dissect disease mechanisms and to develop therapeutic
      approaches.

PMID- 17023148
TI  - Dynamic force spectroscopy on soft molecular systems: improved analysis of
      unbinding spectra with varying linker compliance.
AB  - Dynamic force spectroscopy makes it possible to measure the breaking of single
      molecular bonds or the unfolding of single proteins subjected to a time-dependent
      pulling force. The force needed to break a single bond or to unfold a domain in a
      protein depends critically on the time dependence of the applied force. In this
      way the elastic response couples to the unbinding force. We have performed an
      experimental and theoretical examination of this coupling by studying the well
      known biotin-streptavidin bond in systems incorporating two common types of
      linkers. In the first case biotin is linked by bovine serum albumin (BSA) and it
      is observed that this linker has a linear elastic response. More surprisingly we
      find that its force constant varies significantly between repeated force curves.
      It is demonstrated that by sorting the force curves according to the force
      constant of the linker we can improve the data analysis and obtain a better
      agreement between experimental data and theory. In the second case biotin is
      linked by poly(ethylene glycol) (PEG), which has a soft nonlinear elastic
      response. A numerical calculation of the unbinding statistics for the polymer
      system agrees quantitatively with experiments. It demonstrates a clear decrease
      in unbinding forces resulting from the polymer linker.

PMID- 17023149
TI  - Healthy immune response to allergens: T regulatory cells and more.
AB  - The specific immune response to allergens is decisive in the development of
      clinically healthy or allergic states. In healthy individuals, the B-cell
      response varies between there being no response and the production of IgG(4)- or
      IgG(1)-dominating allergen-specific antibodies in the presence or absence of low
      amounts of IgE. If a detectable immune response is mounted, T regulatory type 1
      (Tr1) cells specific for common environmental allergens consistently represent
      the dominant subset in healthy individuals. Exposure to high doses of allergens
      leads to a high concentration of specific IgG(4), detectable IgE and a Tr1 type
      of immune response. Induction of IL-10- and TGF-beta-producing Tr1 cells, IgG(4)
      isotype blocking antibodies, and suppressed mast cells, basophils and eosinophils
      represent major components of a relatively normalized immune response after
      allergen-specific immunotherapy (SIT).

PMID- 17023150
TI  - Permeability, inflammation and oxidant status in airspace epithelium exposed to
      ozone.
AB  - The aim of the study was to investigate possible mechanisms of epithelial injury
      in normal subjects exposed to environmentally relevant concentrations of ozone.
      Fifteen healthy non-smoking subjects (M:F 12:3) were studied. Five of the 15
      subjects were exposed to filtered air, six were exposed to ozone 100 parts per
      billion (ppb) and seven were exposed to ozone 400 ppb with 99mtechnetium labelled
      diethylene-triamine-penta-acetate (99mTc-DTPA) or bronchoalveolar lavage (BAL)
      performed 1 or 6 h after exposure as indicated above. All the above studies were
      performed on different occasions at least 5 days apart. The subjects were exposed
      on each occasion for 1h during intermittent exercise at a ventilation of 40l min
      1. 99mTc-DTPA lung clearance did not change after either level of ozone exposure,
      but neutrophils increased in BAL 6 h after exposure to 400 ppb. Superoxide anion
      release from mixed BAL leucocytes decreased 1 h after 100 ppb and 6 h after 400
      ppb. Products of lipid peroxidation in epithelial lining fluid decreased both 1
      and 6 h after 400 ppb. There was no change in anti-oxidant capacity or
      glutathione concentrations. Ozone exposure did not increase epithelial
      permeability, but was associated with neutrophil influx into the airspaces,
      without evidence of increased oxidative stress.

PMID- 17023151
TI  - A flexible environmental reuse/recycle policy based on economic strength.
AB  - Environmental policies based on fixed recycling rates may lead to increased
      environmental impacts (e.g., landfilled wastes) during economic expansion. A rate
      policy is proposed, which is adjusted according to the overall strength or
      weakness of the economy, as reflected by overall packaging demand and
      consumption, production and imports-exports. During economic expansion featuring
      rising consumption, production or exports, the proposed flexible policy suggests
      a higher reuse/recycle rate. During economic slowdown a lower rate results in
      lower impacts. The flexible target rates are determined in terms of annual data,
      including consumption, imports-exports and production. Higher environmental gains
      can be achieved at lower cost if the flexible policy is applied to widely
      consumed packaging products and materials associated with low rates, or if
      cleaner recycling technology is adopted.

PMID- 17023152
TI  - Micromorphological investigations into root penetration in a landfill mineral
      cap, Hertfordshire, UK.
AB  - A micromorphological study of the soil fabric of a landfill mineral cap in
      Hertfordshire, UK is described. The study was undertaken to examine the nature of
      the cap and roots within it, and whether micromorphology could help in the
      explanation for root penetration. The results from thin section description
      supported by macro and micro image analysis clearly demonstrated that rooting was
      associated with zones of weakness in the cap, due to the heterogeneous
      particle/pore size distribution, low bulk density and presence of organic matter.
      The study of the material fabric also suggested evidence of pedological activity
      within the cap, further indicating that the mineral cap had not been engineered
      sufficiently to prevent the risk of root penetration. A greater uniformity of
      particle size within the cap material with a reduced clay and stone fraction were
      identified as potential solutions to avoid the extent of root penetration. The
      study demonstrated the value of observing and quantifying the undisturbed fabric
      of the micro structure in the examination of mineral cap fabric, and diagenetic
      and pedological processes acting on it.

PMID- 17023153
TI  - Bacterial oxygenases: in vivo enzyme biosensors for organic pollutants.
AB  - An in vivo enzyme-based biosensor platform was developed that uses specific
      oxygenase enzymes to detect aromatic compounds in water. Bacteria capable of
      degrading highly reduced hydrocarbons initiate substrate oxidation using well
      characterised oxygenase enzymes, which due to their specificity, stability and
      high activity can be applied in vivo as biosensor components. Oxygenase enzyme
      activity was determined in vivo using BD Oxygen Biosensor plates to measure
      oxygenase-mediated oxygen depletion in the presence of specific aromatic
      analytes. The BTEX family of compounds (benzene, toluene, ethylbenzene and the
      three isomers of xylene) were used as model compounds. Detection limits and
      sensitivity achieved using this approach (microM detection range) was similar to
      levels achieved with oxygen electrode-based and some recombinant DNA-based
      approaches. No significant signals were detected with hydrocarbons that were not
      substrates of the initial oxygenases.

PMID- 17023154
TI  - Development and analytical application of an uric acid biosensor using an uricase
      immobilized eggshell membrane.
AB  - An uric acid biosensor fabricated from a uricase-immobilized eggshell membrane
      and an oxygen electrode was presented. The detection schemes involve the
      enzymatic reactions of the uricase leading to the depletion of dissolved oxygen
      level upon exposure to uric acid solution. The decrease in oxygen level was
      monitored and related to the uric acid concentration. The scanning electron
      micrographs show the microstructure of the eggshell membrane within which the
      uricase is successfully immobilized. The effects of enzyme loading, pH,
      temperature, and phosphate buffer concentration on the response of the biosensor
      were investigated in detail. The uric acid biosensor has a linear response range
      of 4.0-640 microM with a detection limit of 2.0 microM (S/N=3). The response time
      was less than 100 s. The biosensor exhibited good repeatable response to a 0.10mM
      uric acid solution with a relative standard deviation of 3.1% (n=7). The
      reproducibility of fabrication of the biosensors using four different membranes
      was good with a R.S.D. of 3.2%. The biosensor showed extremely good stability
      with a shelf-life of at least 3 months. Some common potential interferents in
      samples such as glucose, urea, ascorbic acid, lactic acid, glycine, DL-alpha
      alanine, DL-cysteine, KCl, NaCl, CaCl2, MgSO4, and NH4Cl showed no interferences
      on the response of the uric acid biosensor. The biosensor was successfully
      applied to determine the uric acid level in some human serum and urine samples,
      and the results agreed well with those obtained by a commercial colorimetric
      assay kit.

PMID- 17023155
TI  - Laccase immobilization in redox active layered double hydroxides: a reagentless
      amperometric biosensor.
AB  - This paper describes a new system for amperometric determination of dissolved
      oxygen and its application for the detection of anionic toxic substances, which
      are known as enzyme inhibitors. This biosensor is based on the co-immobilization
      of laccase from Trametes versicolor and a redox active layered double hydroxide
      [Zn-Cr-ABTS] on a glassy carbon electrode. The electrochemical transduction step
      corresponds to the electrocatalytic reduction of O2 at 0.2V by laccase as
      catalyst and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as
      mediator. Such device provides a fast and a sensitive response for dissolved
      oxygen determination between 6 x 10(-8) and 4 x 10(-6)M and very low detection
      limits for azide (5.5 nM), fluoride (6.9 nM) and cyanide (6.2 nM).

PMID- 17023156
TI  - Chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha2b and
      interleukin-2 versus two cycles of dacarbazine followed by chemoimmunotherapy in
      patients with metastatic melanoma: a randomised phase II study of the European
      Organization for Research and Treatment of Cancer Melanoma Group.
AB  - BACKGROUND: Chemoimmunotherapy for patients with metastatic melanoma is
      associated with high toxicity, and only a subset of patients will benefit. This
      randomised phase II study was performed with the primary objective of exploring
      whether two cycles of dacarbazine monotherapy could select the subset of patients
      that would benefit most from more intensive chemoimmunotherapy. PATIENTS AND
      METHODS: Patients with metastatic melanoma were randomised to either receive
      chemoimmunotherapy with dacarbazine, cisplatin, interferon-alpha and interleukin
      2 (arm A) or initial treatment with two cycles of dacarbazine monotherapy
      followed irrespective of response by the same 4-drug regimen of
      chemoimmunotherapy (arm B). Chemoimmunotherapy was continued in the absence of
      disease progression for a maximum of four cycles. Primary end-point was the
      disease stabilisation rate. RESULTS: A total of 93 patients were randomised, and
      89 patients were eligible. Disease stabilisation (complete/partial response or
      stable disease) was achieved in 19 patients (42.2%) in arm A and 9 patients
      (20.5%) in arm B. In arm B 32 of the 44 patients continued chemoimmunotherapy
      after two cycles of dacarbazine. Of 20 patients with progressive disease (PD)
      after two cycles of dacarbazine in arm B, only 2 patients achieved an objective
      response. Median overall survival (OS) in arms A and B was 10.5 months and 9.5
      months, respectively. CONCLUSIONS: Despite a lower initial stabilisation rate,
      the strategy of starting with 2 courses of DTIC prior to a 4-drug regimen led to
      comparable median overall survival. Only few transient responses were achieved
      with the 4-drug regimen in patients with disease progression on DTIC, suggesting
      frequent cross resistance. Two cycles of dacarbazine monotherapy cannot be
      recommended to select patients for more intensive chemoimmunotherapy.

PMID- 17023157
TI  - Standardisation of operating procedures for the detection of minimal disease by
      QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R
      NET.
AB  - The clinical utility of detecting minimal residual disease (MRD) in children with
      neuroblastoma (NB) by quantitative reverse transcriptase polymerase chain
      reaction (QRT-PCR) is not clear. This in part reflects the lack of uniform
      methodology for analysis and reporting. Reference laboratories across Europe have
      therefore established standard operating procedures (SOPs) for the detection of
      NB cells by QRT-PCR. Haemopoietic samples are collected into PAXgene blood RNA
      tubes, which stabilise mRNA for 48 h at room temperature and more than 6 months
      at -80 degrees C. Tyrosine hydroxylase (TH) was selected as the target for NB
      cell detection, expression is normalised to beta2-microglobulin and reported
      using the DeltaDeltaCt method. The sensitivity of QRT-PCR increased from 58% to
      90% following the development of SOPs. A robust, transferable, objective method
      for the detection of NB cells by QRT-PCR has been defined to improve the power
      and consistency of studies on MRD in children with NB.

PMID- 17023158
TI  - Sarcomas and malignant phyllodes tumours of the breast--a retrospective study.
AB  - BACKGROUND: Although most breast cancers are adenocarcinomas of the mammary
      gland, primary breast sarcomas may also arise from mammary gland mesenchymal
      tissue. The annual incidence of primary breast sarcoma is low and has been
      estimated at 45 new cases per 10 million women. These tumours are at high risk of
      recurrence and are known to have poor prognosis. Phyllodes tumours represent a
      specific subset of these breast soft tissue tumours. They are composed of a
      connective tissue stroma and epithelial elements. Pathological presentation
      ranges from grade I to malignant phyllodes tumours (grade III) where the stromal
      component clearly exhibits a sarcoma pattern. MATERIALS AND METHODS: SAPHYR
      (SArcoma and PHYllode Retrospective) is a retrospective study of the experience
      of Leon Berard Cancer Centre (Lyon, France) from 1966 to August 2004. SAPHYR aims
      to describe the characteristics of primary breast sarcomas and to define
      potential survival factors to be evaluated in future prospective studies.
      RESULTS: We included 70 patients. Half of them presented at least one recurrence
      (35/70). Median disease-free-survival (DFS) was 1.15 years. At 3 years, median
      overall survival had not been reached and more than 61% of the patients were
      alive. Quality of surgical resection was significantly (p=0.036) different
      whether patients were in the R0 group (72%) or not (38%). No survival difference
      was found between malignant phyllodes (grade III) and other primary breast
      sarcomas (angiosarcomas excluded). Histology revealed three significantly
      (p=0.0003) different prognostic groups: phyllodes grade I and II (DFS=57%),
      angiosarcomas (DFS=7%) and phyllodes grade III and other primary breast sarcomas
      (DFS=45%). DISCUSSION: Phyllodes tumours and primary breast sarcomas are totally
      different from epithelial breast cancers and should be considered as a distinct
      group of rare tumours. The first goal of treatment is to achieve negative margins
      (R0). We propose to treat the patients according to the clinical practice
      guidelines in use for soft tissue sarcomas and address them to a reference centre
      for sarcoma. Treating rare tumours in the same place should permit us to
      standardise pathological data and to include patients into multicentric
      radiotherapy or chemotherapy protocols to improve overall survival. As further
      prospective studies are needed, European oncology groups must join their forces
      to create a prospective Rare Cancer Network.

PMID- 17023160
TI  - Methodological issues in the economic analysis of cancer treatments.
AB  - Cost-effectiveness analysis may be applied to the full range of interventions
      that make up a cancer service, including screening programmes and early
      treatments, diagnostic test and referral processes, surgery, radiotherapy,
      chemotherapy and palliative care. Numerous methodologies have been employed
      within existing models of cancer interventions. However, not all methodologies
      are equal; inappropriate modelling approaches may bias cost-effectiveness
      results. Generic guidelines for good practice in decision-analytic modelling
      provide a useful basis for critically appraising cost-effectiveness models, yet
      explicit consideration of a range of cancer-specific issues is required to avoid
      bias in cost-effectiveness results. These cancer-specific issues include the
      appropriate representation of relevant costs and health effects associated with
      unplanned treatments for metastatic disease administered beyond disease
      progression, the appropriate extrapolation of long-term outcomes and resources
      from clinical trials, assumptions concerning the nature of the event hazard
      function beyond the duration of the trial, and relationships between surrogate
      outcomes and final outcomes.

PMID- 17023159
TI  - Gene expression profilers and conventional clinical markers to predict distant
      recurrences for premenopausal breast cancer patients after adjuvant chemotherapy.
AB  - A large proportion of breast cancer patients are treated with adjuvant
      chemotherapy after the primary operation, but some will recur in spite of this
      treatment. In order to achieve an improved and more individualised therapy, our
      knowledge in mechanisms for drug resistance needs to be increased. We have
      investigated to what extent cDNA microarray measurements could distinguish the
      likelihood of recurrences after adjuvant CMF (cyclophosphamide, methotrexate and
      5-fluorouracil) treatment of premenopausal, lymph node positive breast cancer
      patients, and have also compared this with the corresponding performance when
      using conventional clinical variables. We tried several gene selection
      strategies, and built classifiers using the resulting gene lists. The best
      performing classifier with odds ratio (OR)=6.5 (95% confidence interval (CI)=1.4
      62) did not outperform corresponding classifiers based on clinical variables. For
      the clinical variables, calibrated on the samples, either using all the clinical
      parameters or the Nottingham Prognostic Index (NPI) parameters, the areas under
      the receiver operating characteristics (ROC) curve were 0.78 and 0.79,
      respectively. The ORs at 90% sensitivity were 15 (95% CI=3.1-140) and 10 (95%
      CI=2.1-97), respectively. Our data have provided evidence for a comparable
      prediction of clinical outcome in CMF-treated breast cancer patients using
      conventional clinical variables and gene expression based markers.

PMID- 17023161
TI  - Oil cakes and their biotechnological applications--a review.
AB  - Oil cakes have been in use for feed applications to poultry, fish and swine
      industry. Being rich in protein, some of these have also been considered ideal
      for food supplementation. However, with increasing emphasis on cost reduction of
      industrial processes and value addition to agro-industrial residues, oil cakes
      could be ideal source of proteinaceous nutrients and as support matrix for
      various biotechnological processes. Several oil cakes, in particular edible oil
      cakes offer potential benefits when utilized as substrate for bioprocesses. These
      have been utilized for fermentative production of enzymes, antibiotics,
      mushrooms, etc. Biotechnological applications of oil cakes also include their
      usages for vitamins and antioxidants production. This review discusses various
      applications of oil cakes in fermentation and biotechnological processes, their
      value addition by implementation in feed and energy source (for the production of
      biogas, bio-oil) as well.

PMID- 17023162
TI  - Age-related slip avoidance strategy while walking over a known slippery floor
      surface.
AB  - When confronted with impending slip/fall situations, gait parameters are adjusted
      accordingly to avoid slipping. This study was conducted to assess age-related
      slip avoidance strategy by measuring gait parameters and muscle activity
      characteristics of the lower extremities (hamstrings, calves, and quadriceps) of
      both young and older participants while ambulating successfully over a known
      slippery floor surface. Fourteen younger and 14 older adults participated in this
      study. First, a baseline measure was collected to study normal gait prior to any
      exposure to slipping. A second measure was collected following a slip from a
      contaminated floor surface, but before the initiation of a second slip, where the
      participants were able to view the contaminated surface before traversing it. The
      results indicated that there were significant gait parameter differences between
      normal-dry walking conditions and contaminated-slippery walking conditions. In
      general, participants (young and old) reduced step length, friction utilization,
      and heel contact velocity from normal gait to adjusted gait conditions.
      Furthermore, results also indicated that there were differences in gait
      parameters and muscle activity characteristics between the two age groups for
      both a normal gait condition and a gait condition requiring adjustment. Findings
      suggested that older individuals required an additional step to properly adjust
      gait for a contaminated walking surface.

PMID- 17023163
TI  - Yield and purity of 82Sr produced via the natRb(p,xn) 82Sr process.
AB  - The recently reported cross-section data for the production of 82Sr via the
      natRb(p,xn) 82Sr process were evaluated. For the natRb(p,xn) 85Sr process, cross
      sections were measured experimentally over the proton energy range of 25-45 MeV,
      a region where very few data existed. An evaluation of the recently published
      data on the formation of 85Sr was then also performed. From the recommended data
      curves, the integral yields of the desired radionuclide 82Sr and the impurity
      85Sr were calculated. Yields were also determined experimentally over several
      energy ranges using thick natRbCl targets. The experimental and calculated yields
      were found to be in agreement within 15%. These integral tests add confidence to
      the evaluated cross-section data. For the production of 82Sr, an incident proton
      energy of 60 MeV or above is recommended; the 85Sr impurity then corresponds to
      <20%.

PMID- 17023164
TI  - Peripheral inflammation and neuroprotection: systemic pretreatment with complete
      Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of
      Parkinson's disease.
AB  - Complete Freund's adjuvant (CFA), a pro-inflammatory agent, was inoculated,
      subcutaneously, to Sprague-Dawley rats prior to the intrastriatal injection of 6
      hydroxydopamine (6-OHDA). Animals were sacrificed 7 and 28 days following 6-OHDA
      injection; neuronal damage, glial activation and cytokine levels, within the
      nigrostriatal system, were then investigated. Nigrostriatal degeneration induced
      by 6-OHDA was accompanied by early microglial and astroglial activation, which
      preceded the onset of dopaminergic cell loss, in the SNc, without significant
      changes in cytokine levels. CFA pretreatment markedly reduced the SNc neuronal
      loss and associated microglial activation, as well as the rotational response to
      apomorphine. These changes were associated with moderate, transient increases in
      the nigrostriatal levels of glial-cell-derived neurotrophic factor (GDNF) and pro
      inflammatory cytokines, including interleukin (IL)-1alpha, IL-1beta and IL-6. Our
      results show that prior delivery of a peripheral, pro-inflammatory stimulus
      induces neuroprotection, in a rodent model of Parkinson's disease, possibly
      through the modulation of cytokine production at the nigrostriatal level.

PMID- 17023165
TI  - Plant glycoside hydrolases involved in cell wall polysaccharide degradation.
AB  - The cell wall plays a key role in controlling the size and shape of the plant
      cell during plant development and in the interactions of the plant with its
      environment. The cell wall structure is complex and contains various components
      such as polysaccharides, lignin and proteins whose composition and concentration
      change during plant development and growth. Many studies have revealed changes in
      cell walls which occur during cell division, expansion, and differentiation and
      in response to environmental stresses; i.e. pathogens or mechanical stress.
      Although many proteins and enzymes are necessary for the control of cell wall
      organization, little information is available concerning them. An important
      advance was made recently concerning cell wall organization as plant enzymes that
      belong to the superfamily of glycoside hydrolases and transglycosidases were
      identified and characterized; these enzymes are involved in the degradation of
      cell wall polysaccharides. Glycoside hydrolases have been characterized using
      molecular, genetic and biochemical approaches. Many genes encoding these enzymes
      have been identified and functional analysis of some of them has been performed.
      This review summarizes our current knowledge about plant glycoside hydrolases
      that participate in the degradation and reorganisation of cell wall
      polysaccharides in plants focussing particularly on those from Arabidopsis
      thaliana.

PMID- 17023166
TI  - Structural and functional analysis of a salt stress inducible gene encoding
      voltage dependent anion channel (VDAC) from pearl millet (Pennisetum glaucum).
AB  - We have cloned and characterized a gene encoding voltage-dependent anion channel
      from Pennisetum glaucum (PgVDAC). PgVDAC was identified while isolating genes
      that were differentially up-regulated following salt stress. The genomic
      organization of PgVDAC clone was well conserved compared to other plant VDAC
      genes in terms of number of introns, their position and phasing, however, the
      primary amino acid sequence of voltage dependent anion channel (VDAC) proteins
      did not show much conservation with other plant VDACs but their secondary and
      tertiary structures are well conserved as predicted by in silico structural and
      CD spectra analyses and results show it to be a typical membrane-spanning beta
      barrel leading to the formation of pore in the membrane. The heterologous
      expression of PgVDAC protein in yeast strain lacking the endogenous mitochondrial
      VDAC gene could not functionally complement it as was also previously observed
      for the potato VDAC. Using real-time quantitative PCR analysis it was found that
      transcript expression profile of PgVDAC was quantitatively and kinetically up
      regulated in response to salinity, desiccation, cold and exogenous application of
      salicylic acid (SA); however, there was no effect of exogenous application of
      abscisic acid (ABA) on its expression. Constitutive over-expression of PgVDAC
      appears to be deleterious in transgenic rice plant; however, low level of up
      regulation imparted salinity stress adaptive response. A search for a more
      suitable inducible transgene system is currently under way to understand PgVDAC
      expression levels in plant development and its role in stress adaptation.

PMID- 17023167
TI  - High performance liquid chromatography method for the determination of cinnamyl
      alcohol dehydrogenase activity in soybean roots.
AB  - This study proposes a simple, quick and reliable method for determining the
      cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) activity in soybean (Glycine
      max L. Merr.) roots using reversed-phase high performance liquid chromatography
      (RP-HPLC). The method includes a single extraction of the tissue and conduction
      of the enzymatic reaction at 30 degrees C with cinnamaldehydes (coniferyl or
      sinapyl), substrates of CAD. Disappearance of the substrates in the reaction
      mixture is monitored at 340 nm (for coniferaldehyde) or 345 nm (for
      sinapaldehyde) by isocratic elution with methanol/acetic acid through a GLC-ODS
      (M) column. This HPLC technique furnishes a rapid and reliable measure of
      cinnamaldehyde substrates, and may be used as an alternative tool to analyze CAD
      activity in enzyme preparation without previous purification.

PMID- 17023168
TI  - The lysine-ketoglutarate reductase-saccharopine dehydrogenase is involved in the
      osmo-induced synthesis of pipecolic acid in rapeseed leaf tissues.
AB  - Higher plant responses to abiotic stresses are associated with physiological and
      biochemical changes triggering a number of metabolic adjustments. We focused on L
      lysine catabolism, and have previously demonstrated that degradation of this
      amino acid is osmo-regulated at the level of lysine-ketoglutarate reductase (LKR,
      EC 1.5.1.8) and saccharopine dehydrogenase (SDH, EC 1.5.1.9) in Brassica napus.
      LKR and SDH activities are enhanced by decreasing osmotic potential and decrease
      when the upshock osmotic treatment is followed by a downshock osmotic one.
      Moreover we have shown that the B. napus LKR/SDH gene is up-regulated in
      osmotically-stressed tissues. The LKR/SDH activity produces alpha-aminoadipate
      semialdehyde which could be further converted into alpha-aminoadipate and acetyl
      CoA. Alternatively alpha-aminoadipate could behave as a precursor for pipecolic
      acid. Pipecolic acid is described as an osmoprotectant in bacteria and is co
      accumulated with proline in halophytic plants. We suggest that osmo-induction of
      the LKR/SDH activity could be partly responsible for pipecolic acid accumulation.
      This proposal has been assessed in this study through pipecolic acid amounts
      determination in rape leaf discs subjected to various upshift and downshift
      osmotic treatments. Changes in pipecolic acid level actually behave as those
      observed for LKR and SDH activities, since it increases or decreases in rape leaf
      discs treated under hyper- or hypo-osmotic conditions, respectively. In addition
      we show that pipecolic acid level is positively correlated with the external
      osmotic potential as well as with the duration of the applied treatment. On the
      other hand pipecolic acid level is related to the availability of L-lysine and
      not to that of D-lysine. Collectively the results obtained demonstrate that
      lysine catabolism through LKR/SDH activity is involved in osmo-induced synthesis
      of pipecolic acid.

PMID- 17023169
TI  - Molecular characterisation of a Tuber borchii Smt3 gene.
AB  - Tbsmt3 gene from the ectomychorrizal fungus Tuber borchii was identified and
      sequenced. The Tbsmt3 gene encodes for a protein sharing significant amino acid
      homology with the yeast SMT3, a ubiquitin-like protein that is post
      translationally attached to several proteins involved in many cellular processes.
      The comparison between the Tbsmt3 genomic and cDNA sequences established that the
      encoding sequence is interrupted by an intron of 312 bp. Southern blot analysis
      revealed only one copy of Tbsmt3 gene in the T. borchii genome. Tbsmt3 is
      expressed in all phases of T. borchii life cycle: mycelium, ectomycorrhiza and
      ascoma. However, the Tbsmt3 mRNA decreased during fruit body maturation.

PMID- 17023170
TI  - Increased ascorbate content delays flowering in long-day grown Arabidopsis
      thaliana (L.) Heynh.
AB  - Flowering requires the integration of different inductive stimuli, including
      light, temperature and hormones. In an attempt to assess whether ascorbate (ASC)
      could contribute to the control of flowering time, we analyzed the effects of
      increased ASC content on the transition to the reproductive stage in the
      facultative long-day plant Arabidopsis thaliana. ASC content was increased by
      spraying leaves with the ASC precursor L-galactono-gamma-lactone. Our data show
      that increased ASC content did not affect vegetative growth, whereas a
      significant delay (5 days in average) in flower production occurred in ASC
      overproducing plants. Higher ASC availability resulted in delayed expression of
      LEAFY (LFY), the gene encoding for a key transcription factor integrating
      different flowering-inductive pathways. On the contrary, spraying with
      gibberellin under the same condition caused both early LFY expression and early
      flowering. The possible role of ASC in the transition to the reproductive stage
      is discussed.

PMID- 17023171
TI  - Induction of acid phosphatase activity during germination of maize (Zea mays)
      seeds.
AB  - Acid phosphatase activity (orthophosphoric-monoester phosphohydrolase, EC
      3.1.3.2) increased during the first 24 h of maize (Zea mays) seed germination.
      The enzyme displayed a pH optimum of 4.5-5.5. Catalytic activity in vitro
      displayed a linear time course (60 min) and reached its half maximum value at
      0.47 mM p-nitrophenyl phosphate (pNPP). Phosphatase activity towards phosphoamino
      acids was greatest for phosphotyrosine. The phosphatase activity was strongly
      inhibited by ammonium molybdate, vanadate and NaF and did not require divalent
      cations for the catalysis. The temperature optimum for pNPP hydrolysis was 37
      degrees C. Under the same conditions, no enzyme activity was detected with phytic
      acid as substrate. Western blotting of total homogenates during seed germination
      revealed proteins/polypeptides that were phosphorylated on tyrosine residues; a
      protein of approximately 14 kDa is potentially a major biological substrate for
      the phosphatase activity. The results presented in this study suggest that the
      acid phosphatase characterized under the tested conditions is a member of the
      phosphotyrosine phosphatase family.

PMID- 17023172
TI  - The impact of left ventricular reconstruction on survival in patients with
      ischemic cardiomyopathy.
AB  - OBJECTIVE: Left ventricular reconstruction (LVR) is performed to improve the
      morphologic structure and function of the heart in patients with heart failure.
      This procedure has been performed at the Cleveland Clinic Foundation since 1997.
      We assessed mortality, functional status, and predictors of outcome in these
      patients. METHODS: Data were extracted from multiple prospectively acquired
      datasets on demographic, clinical, and operative details of 220 consecutive
      patients who underwent LVR between July 1997 and July 2003, where the indication
      for surgery was heart failure (of whom 66% had New York Heart Association (NYHA)
      functional class III or IV symptoms). Mortality, functional status, and
      postoperative complications were ascertained by reference to the clinical record,
      social security death index, and by phone contact. Mean preoperative left
      ventricular ejection fraction (LVEF) was 21.5+/-7.3% and mean left ventricular
      end-diastolic diameter was 6.4+/-1.0 cm. The mean age was 61.4+/-9.0 years and
      80% were male. The majority (86%) of patients underwent concomitant coronary
      artery bypass grafting and 49% underwent mitral valve surgery. RESULTS: Thirty
      day mortality was 1% and survival at 1, 3, and 5 years was 92%, 90%, and 80%,
      respectively. Of the survivors for whom data on NYHA functional class were
      available, 85% were in NYHA functional class I or II. Mortality was predicted by
      reduced preoperative ejection fraction <20% (unadjusted hazard ratio 1.53, p =
      0.02), body mass index < or = 24 kg/m2 (unadjusted hazard ratio 1.69, p = 0.01),
      QRS duration > or = 130 ms (unadjusted hazard ratio 1.66, p = 0.01) and the
      requirement for renal replacement therapy postoperatively (unadjusted hazard
      ratio 3.85, p < 0.01). Mean LVEF improved to 24.7+/-8.86% (p < 0.01) and left
      ventricular volumes were also significantly reduced. CONCLUSIONS: In selected
      patients with heart failure, LVR, in conjunction with revascularization and valve
      surgery, is associated with excellent survival, improved symptoms, and improved
      LVEF and left ventricular dimensions.

PMID- 17023173
TI  - Decitabine--bedside to bench.
AB  - PURPOSE OF THE REVIEW: Epigenetic changes marked by DNA methylation are known to
      contribute to the malignant transformation of cells by silencing critical genes.
      Decitabine inhibits DNA methyltransferase and has shown therapeutic effects in
      patients with hematologic malignancies. However, the connection between the
      clinical activity of decitabine and its demethylating activity is not clear.
      Herein, we summarize the results of recent clinical trials of decitabine in
      hematologic malignancies, and review the translational research into decitabine's
      mechanism of clinical activity. RECENT FINDINGS: Low-dose decitabine has been
      studied recently in multiple clinical trials and has been shown to be effective
      for treatment of myelodysplastic syndromes. Correlative laboratory studies of
      clinical trials have shown that decitabine induces global hypomethylation as well
      as hypomethylation of gene-specific promoters and activation of gene expression.
      Past a given threshold, induction of higher degrees of hypomethylation is not
      directly associated with a better clinical outcome. Moreover, studies have
      suggested that patients with promoter hypermethylation of p15(INK4B) at baseline
      have paradoxically a lower chance of achieving response than those without
      hypermethylation. Furthermore, several other genes activated by decitabine were
      independent of hypomethylation in the promoter regions. CONCLUSION: While at
      least part of decitabine's activity is through induction of hypomethylation and
      reactivation of critical genes, mechanisms independent from hypomethylation are
      also important for decitabine's antitumor activity.

PMID- 17023174
TI  - Does age matter in palliative care?
AB  - PURPOSE: To assess whether age has an impact on symptoms, problems and needs of
      hospitalized advanced cancer patients. PATIENTS AND METHODS: A prospective
      analysis of 181 patients referred to a Palliative Care Team was done using a
      standardized list of symptoms, problems and needs. Differences between 3 age
      groups (<60; 60-70; > or =70) were analyzed. RESULTS: Patients > or =70 years had
      a significantly different prevalence of depressed mood (48% versus 13% of
      patients 60-70 years and 24% of patients <60 years, p=0.002), urinary tract
      problems (20% versus 3% versus 8%, p=0.024) and drowsiness (18% versus 42% versus
      25%, p=0.039). They expressed more problems with a shortage of informal
      caregivers (45% versus 42% versus 17%, p<0.001) and less need for support in
      coping (40% versus 61% versus 63%, p=0.043), relational support (3% versus 8%
      versus 14%, p=0.019) and support in communication (0% versus 8% versus 11%,
      p=0.013). CONCLUSION: Fewer differences than expected were found. Elderly cancer
      patients admitted to a hospital have more or less the same symptoms, problems and
      needs as their younger counterparts. Despite these findings, age-specific
      assessment of symptoms, problems and needs ought to be part of optimal symptom
      management.

PMID- 17023175
TI  - Noncovalent complexes of APS reductase from M. tuberculosis: delineating a
      mechanistic model using ESI-FTICR MS.
AB  - ESI-FTICR MS was utilized to characterize a 4Fe-4S containing protein
      Mycobacterium tuberculosis APS reductase. This enzyme catalyzes the reduction of
      APS to sulfite and AMP with reducing equivalents from the protein cofactor,
      thioredoxin. Under nondenaturing conditions, a distribution of the apoprotein, a
      2Fe-2S intermediate, and the 4Fe-4S holoprotein were observed. Accurate mass
      measurements indicated an oxidation state of +2 for the 4Fe-4S cluster, with no
      disulfide bond in the holoenzyme. Gas-phase stability of the 4Fe-4S cluster was
      investigated using both in-source and collision induced dissociation, which
      provided information regarding the relative gas-phase binding strength of iron
      towards protein ligands and inorganic sulfides. Noncovalent complexes of the
      holoprotein with several ligands, including APS, thioredoxin, and AMP, were also
      investigated. Calculated values of dissociation constants for the complexes
      indicate that AMP binds with a higher affinity to the enzyme intermediate than to
      the free enzyme. The implications of the binary and ternary complexes observed by
      gas-phase noncovalent interactions in the mechanism of APS reduction are
      discussed.

PMID- 17023176
TI  - Mendelian and complex genetics of susceptibility and resistance to parasitic
      infections.
AB  - Uncovering the complex genetic basis of susceptibility and resistance to
      parasitic infectious diseases is an enormous challenge. It probably involves many
      different host genes, interacting with multiple parasite genetic and
      environmental factors. Several genes of interest have been identified by family
      and association studies in humans and by using mouse models, but more robust
      epidemiological studies and functional data are needed to authenticate these
      findings. With new technologies and statistical tools for whole-genome
      association analysis, the next few years are likely to see acceleration in the
      rate of gene discovery, which has the potential to greatly assist drug and
      vaccine development.

PMID- 17023177
TI  - Common variable immunodeficiency: The power of co-stimulation.
AB  - Common variable immunodeficiency (CVID) is the most frequent symptomatic primary
      immune deficiency in adults. CVID is characterized by the sequelae of an antibody
      deficiency syndrome: an impaired terminal B cell differentiation results in
      hypogammaglobulinemia and susceptibility to recurrent infections by encapsulated
      bacteria. The clinical course of CVID is complicated by a plethora of systemic
      immunopathology, including autoimmunity, lymphoproliferation, malignancy and
      sarcoid-like granulomas. Phenotypic and functional studies in CVID patients
      revealed multiple abnormalities within the innate and adaptive immune system. The
      recent description of monogenic defects in ICOS, TACI and CD19 focussed our
      interest to an impaired T cell-B cell collaboration within the germinal center
      and intrinsic B cell defects as possible explanations for the etiology of CVID.

PMID- 17023178
TI  - Structural characterization of beta-sheeted oligomers formed on the pathway of
      oxidative prion protein aggregation in vitro.
AB  - The pathology of transmissible spongiform encephalopathies (TSEs) is strongly
      associated with the structural conversion of the cellular prion protein (PrPC)
      into a misfolded isoform (PrPSc) that assembles into amyloid fibrils. Since
      increased levels of oxidative stress have been linked to prion diseases, we
      investigated the metal-induced oxidation of human PrP (90-231). A novel in vitro
      conversion assay based on aerobic incubation of PrP in the presence of elemental
      copper pellets at pH 5 was established, resulting in aggregation of highly beta
      sheeted prion proteins. We show for the first time that two discrete oligomeric
      species of elongated shape, approx. 25 mers and 100 mers, are formed on the
      pathway of oxidative PrP aggregation in vitro, which are well characterized
      regarding shape and size using small-angle X-ray scattering (SAXS), dynamic light
      scattering (DLS), and electron microscopy (EM). Considering that small oligomers
      of highly similar size have recently been reported to show the highest specific
      infectivity within TSE-infected brain tissues of hamsters, the novel oligomers
      observed in this study are interesting candidates as agent causing
      neurodegenerative and/or self-propagating effects. Moreover, our results
      significantly strengthen the theory that oxidative stress might be an influence
      that leads to substantial structural conversions of PrP in vivo.

PMID- 17023179
TI  - Prefrontal and hippocampal contributions to the generation and binding of
      semantic associations during successful encoding.
AB  - The ability to form and bind associations between items is an important aspect of
      successful memory formation. We hypothesize that, during encoding, the left
      inferior frontal gyrus (IFG) supports generation of associations between items
      and the hippocampus then binds these associations. This study examined the
      parametric responses of these regions to varying amounts of generative and
      relational processing during successful encoding (i.e., for subsequently
      recognized items). Encoding involved presentation of word triads varying in the
      number of semantic associations among them (none, one or all); participants
      judged how many associations were present in each triad. Thus, triads with fewer
      associations had higher generative load while triads with more associations had
      higher relational load. Participants later completed a forced-choice recognition
      test for encoding triads. Successful encoding relative to a control task resulted
      in activation of bilateral IFG and left hippocampus, and the hippocampus also
      exhibited a significant subsequent memory effect (hits>misses). Linear parametric
      analyses revealed that generative load modulated activity in bilateral IFG while
      relational load correlated with activity in left hippocampus. Although univariate
      analyses distinguished IFG and hippocampal contributions to the generative and
      relational stages of encoding, respectively, effective connectivity between these
      regions did not differ according to condition. Furthermore, this analysis
      revealed that the left IFG played a pivotal role in coordinating associative
      encoding processes. Our findings illustrate that modulation of components in a
      memory network can be independent of patterns of mutual connectivity among those
      components in mediating successful encoding.

PMID- 17023180
TI  - A cross-laboratory study of event-related gamma activity in a standard object
      recognition paradigm.
AB  - This study proposes a standard paradigm for the investigation of visual
      information processing by means of gamma activity and presents a novel set of
      stimuli with a broad range of complex, coloured familiar real world and
      unfamiliar nonsense objects which are well matched with respect to physical
      stimulus properties. In order to demonstrate that the paradigm and stimulus set
      yield reliable results both were employed in two electrophysiological
      investigations in two independent laboratories. Participants were required to
      discriminate familiar from unfamiliar stimuli. The pattern of results was very
      consistent across laboratories. Early event-related potentials were not
      influenced by the stimulus type suggesting that physical stimulus properties did
      not confound object familiarity. Induced gamma band activity was stronger for
      familiar than for unfamiliar objects, supporting the notion of gamma activity as
      a signature of cortical networks underlying object representations.

PMID- 17023181
TI  - Synchronization likelihood with explicit time-frequency priors.
AB  - Cognitive processing requires integration of information processed simultaneously
      in spatially distinct areas of the brain. The influence that two brain areas
      exert on each others activity is usually governed by an unknown function, which
      is likely to have nonlinear terms. If the functional relationship between
      activities in different areas is dominated by the nonlinear terms, linear
      measures of correlation may not detect the statistical interdependency
      satisfactorily. Therefore, algorithms for detecting nonlinear dependencies may
      prove invaluable for characterizing the functional coupling in certain neuronal
      systems, conditions or pathologies. Synchronization likelihood (SL) is a method
      based on the concept of generalized synchronization and detects nonlinear and
      linear dependencies between two signals (Stam, C.J., van Dijk, B.W., 2002.
      Synchronization likelihood: An unbiased measure of generalized synchronization in
      multivariate data sets. Physica D, 163: 236-241.). SL relies on the detection of
      simultaneously occurring patterns, which can be complex and widely different in
      the two signals. Clinical studies applying SL to electro- or
      magnetoencephalography (EEG/MEG) signals have shown promising results. In
      previous implementations of the algorithm, however, a number of parameters have
      lacked a rigorous definition with respect to the time-frequency characteristics
      of the underlying physiological processes. Here we introduce a rationale for
      choosing these parameters as a function of the time-frequency content of the
      patterns of interest. The number of parameters that can be arbitrarily chosen by
      the user of the SL algorithm is thereby decreased from six to two. Empirical
      evidence for the advantages of our proposal is given by an application to EEG
      data of an epileptic seizure and simulations of two unidirectionally coupled
      Henon systems.

PMID- 17023182
TI  - Pharmacological MRI in awake rats reveals neural activity in area postrema and
      nucleus tractus solitarius: relevance as a potential biomarker for detecting drug
      induced emesis.
AB  - Drug-induced vomiting (emesis) is a major concern in patient care and a
      significant hurdle in the development of novel therapeutics. With respect to the
      latter, rodents, such as the rat and mouse, are typically used in efficacy and
      safety studies; however, drug-induced emesis cannot be readily observed in these
      species due to the lack of an emetic reflex. It is known that emesis can be
      triggered by neural activity in brain regions including area postrema (AP) and
      nucleus tractus solitarius (NTS). In this study, using pharmacological magnetic
      resonance imaging (phMRI) and a blood-pool contrast agent, we imaged the
      hemodynamic consequences of brain activity in awake rats initiated by the
      administration of compounds (apomorphine 0.1, 0.3 micromol/kg i.v. and ABT-594
      0.03, 0.1, 0.3 micromol/kg i.v.) that elicit emesis in other species. Regional
      drug-induced relative cerebral blood volume (rCBV) changes and percent activated
      area within the AP and NTS were calculated, in which a dose-dependent
      relationship was evident for both apomorphine and ABT-594. Additionally, to
      correlate with behavioral readouts, it was found that the activation of AP and
      NTS was observed at plasma concentrations consistent with those that induced
      emesis in ferrets for both drugs. Our data thus suggest that phMRI in awake rats
      may be a useful tool for predicting emetic liability of CNS-acting drugs and may
      provide insights into depicting the underlying emetic neural pathways in vivo.

PMID- 17023183
TI  - An electrophysiological link between the cerebellum, cognition and emotion:
      frontal theta EEG activity to single-pulse cerebellar TMS.
AB  - Early intracranial electrical stimulation studies in animals demonstrated
      cerebellar connectivity to brain structures involved in cognitive and emotive
      functions. Human electrophysiological data to support cerebellum involvement in
      the latter functions are however lacking. In the present study,
      electrophysiological responses were recorded to single-pulse transcranial
      magnetic stimulation (TMS) over the vermis in healthy human volunteers. Increased
      theta activity was observed after single-pulse vermis TMS as compared to sham and
      occipital TMS. Both animal and human research relate theta activity with the
      septo-hippocampal complex, an important brain structure involved in cognition and
      emotion. The present electrophysiological study supports the earlier intracranial
      electrical stimulation findings by demonstrating cerebellar involvement in the
      modulation of the core frequencies related to cognitive and emotive aspects of
      human behavior.

PMID- 17023184
TI  - Connectivity-based parcellation of human cortex using diffusion MRI: Establishing
      reproducibility, validity and observer independence in BA 44/45 and SMA/pre-SMA.
AB  - The identification of specialized, functional regions of the human cortex is a
      vital precondition for neuroscience and clinical neurosurgery. Functional imaging
      modalities are used for their delineation in living subjects, but these methods
      rely on subject cooperation, and many regions of the human brain cannot be
      activated specifically. Diffusion tractography is a novel tool to identify such
      areas in the human brain, utilizing underlying white matter pathways to separate
      regions of differing specialization. We explore the reproducibility,
      generalizability and validity of diffusion tractography-based localization in
      four functional areas across subjects, timepoints and scanners, and validate
      findings against fMRI and post-mortem cytoarchitectonic data. With
      reproducibility across modalities, clustering methods, scanners, timepoints, and
      subjects in the order of 80-90%, we conclude that diffusion tractography
      represents a useful and objective tool for parcellation of the human cortex into
      functional regions, enabling studies into individual functional anatomy even when
      there are no specific activation paradigms available.

PMID- 17023185
TI  - Diffusion tensor imaging of the corpus callosum in Autism.
AB  - The corpus callosum is the largest commissural white matter pathway that connects
      the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI)
      was performed on subject groups with high-functioning autism and controls matched
      for age, handedness, IQ, and head size. DTI and volumetric measurements of the
      total corpus callosum and subregions (genu, body and splenium) were made and
      compared between groups. The results showed that there were significant
      differences in volume, fractional anisotropy, mean diffusivity, and radial
      diffusivity between groups. These group differences appeared to be driven by a
      subgroup of the autism group that had small corpus callosum volumes, high mean
      diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had
      significantly lower performance IQ measures than either the other individuals
      with autism or the control subjects. Measurements of radial diffusivity also
      appeared to be correlated with processing speed measured during the performance
      IQ tests. The subgroup of autism subjects with high mean diffusivity and low
      fractional anisotropy appeared to cluster with the highest radial diffusivities
      and slowest processing speeds. These results suggest that the microstructure of
      the corpus callosum is affected in autism, which may be related to nonverbal
      cognitive performance.

PMID- 17023186
TI  - Effect of interseizure interval on seizure lateralization in patients with
      bilateral seizure foci.
AB  - We investigated whether there is a cluster effect depending on localization of
      seizure foci in patients with bilateral seizure foci. We evaluated 171 seizure
      pairs from 193 seizures recorded in 28 patients. Seizure lateralization was
      determined by the lateralization of ictal discharges; if the ictal EEG pattern
      was not lateralized, lateralization was determined by clinical seizure semiology.
      The logarithm of the interseizure interval (ISI) was significantly related to
      seizure concordance only in patients with extratemporal seizure foci, but not in
      those with bitemporal foci. In the former group, the mean ISI for concordant
      seizure pairs was significantly shorter than that for discordant seizures pairs
      (292 min versus 631 min, p=0.023). Seizure types composing seizure pairs had a
      significant influence on ISI regardless of the localization of seizure foci. ISIs
      were shortest in seizure pairs with only partial seizures. However, types of
      seizure pairs were significantly related to concordance rates of seizure
      lateralization only in patients with extratemporal foci (p=0.005). In conclusion,
      our results suggest that the cluster effect on seizure localization exists in
      patients with extratemporal seizure foci, but not in those with bitemporal foci.

PMID- 17023187
TI  - Shape effects on the activity of synthetic major-groove binding ligands.
AB  - In this work we present the results of a molecular simulation study of two
      different tetracationic bis iron(II) supramolecular cylinders interacting with
      DNA. One cylinder has been shown to bind in the major groove of DNA and to induce
      dramatic coiling of the DNA; the second is a derivative of the first, with
      additional methyl groups attached so as to give a larger cylinder-radius. The
      simulations show that both cylinders bind strongly to the major groove of the
      DNA, and induce complex structural changes in A-T rich regions. Whereas the
      parent cylinder tends to bind along the major groove, the derivatised cylinder
      tends to twist so that only one end remains within the major groove. Both G-C
      rich and A-T rich binding sites for the derivatised cylinder are discussed.

PMID- 17023188
TI  - Reliability of radiographic intervertebral disc height measurement for in vivo
      rat-tail model.
AB  - Quantification of changes in intervertebral disc height is critical for studying
      intervertebral disc degeneration. Reliability of disc height measurement is
      therefore especially important for in vivo studies using animal models of disc
      degeneration. In this study, the effects of image intensity and percentage of
      disc width used for disc height measurement from radiographic images were
      evaluated in a rat-tail model. Radiographs were taken for 10 Sprague-Dawley rats
      using a standardized protocol. Average disc heights of the caudal 8-9 discs were
      determined using original and intensity adjusted images with different
      percentages of disc width. The average disc height was found to be significantly
      affected by both the image intensity and the percentage of disc width measured. A
      higher reliability was found in the measurement for image with adjusted intensity
      and using smaller disc width. Image intensity is suggested to be controlled and
      the disc width should be taken into account in quantifying the disc height.

PMID- 17023189
TI  - Femoroplasty--augmentation of the proximal femur with a composite bone cement-
      feasibility, biomechanical properties and osteosynthesis potential.
AB  - BACKGROUND: Analogous to vertebroplasty, cement-augmentation of the proximal
      femur ("femoroplasty") could reinforce osteoporotic bones. This study was to
      evaluate (i) the feasibility of femoroplasty with a composite cement (Cortoss),
      (ii) its influence on femoral strength by mechanical testing and (iii) the
      feasibility of stable osteosynthesis of the augmented fractured bones. METHODS:
      Nine human cadaveric femora were augmented with a composite bone cement, the
      surface heat generation monitored, and then tested biomechanically against their
      native contralateral control to determine fracture strength. Subsequently,
      thirteen reinforced and fractured femora were osteosynthetized by different
      implants and tested against their osteosynthetisized, non-augmented contralateral
      control. FINDINGS: Cement could be injected easily, with a moderate temperature
      rise. A positive correlation between BMD and fracture load and a significant
      increase in fracture load (+43%) of the augmented femora compared to their native
      controls (6324 N and 4430 N, respectively) as well as a significant increase in
      energy-to-failure (+187%, 86 N m and 30 N m, respectively) was found.
      Osteosynthesis was possible in cement-augmented femora. Osteosynthetisized femora
      showed equivalent strength to the intact controls. INTERPRETATION: Augmentation
      of the proximal femur with composite bone cement could be of use in prophylaxis
      of fractures in osteoporotic femurs. Osteosynthesis of the fractured augmented
      bones is a challenging procedure but has a good chance to restore strength.

PMID- 17023190
TI  - Occupational accidents and forensic medicine in Turkey.
AB  - In Turkey, evaluation of the ratio of loss of working capacity is made according
      to various laws and regulations. These laws and regulations use different
      standards in computing the above-mentioned ratio depending on the professional
      status of the worker, whether he or she is a member of SSK (Social Security
      Institution) or ES (The Retirement Pension Institution) system. The aim of this
      study is to point out at the differences and deficiencies in computing the degree
      of disability and at the need to bring common standards to these computations.
      This prospective descriptive research is based on the cases of occupational
      accidents and occupational diseases brought to the 3rd specialized branch of the
      Institution of Forensic Medicine (which is the highest ruling instance concerning
      the decision on this field). Of the 164 accident cases included in this research,
      95.1% are males, and 4.9% females. According to distribution by age of the cases,
      the modal group is respectively (30-39) years for men and (12-19) years for
      women. 43.8% of the injuries were localized at the hand or wrist. No meaningful
      statistical relationship could be found between the level of qualification of the
      workers (skilled-unskilled) and the proportion of those suffering from total
      disability. For the cases included in the categories 3, 4 and 5 is the ES system;
      the ratio of disability was similar to those computed according to the SSK
      system. In conclusion, we would like to insist on the need for our country to
      amend our laws and regulations according to changing and prevailing conditions
      and sex differentials and to bring homogeneous standards for all workers.

PMID- 17023191
TI  - Fatal poisoning in the region of Epirus, Greece, during the period 1998-2004.
AB  - The aim of this study was to assess the characteristics of acute poisoning deaths
      in the deprived region of Epirus, north-west Greece, as they were recorded among
      the autopsies performed at the Department of Forensic Medicine and Toxicology,
      Medical School, University of Ioannina, Greece. A retrospective study of the
      forensic records and the toxicological data of all autopsies performed over the
      period 1998-2004 revealed that 46 cases (2.9%) out of the 1582 total autopsies
      performed were attributed to acute fatal poisoning. The age range was from 16 to
      94 years (mean+/-SD=46.20+/-22.13). Substances of abuse were implicated in 22
      cases (47.8%), pesticides in 9 cases (19.6%), gases in eight cases (17.4%),
      corrosives in 4 cases (8.7%), and prescription drugs in 3 cases (6.5%). There
      were 35 males (76.1%) and 11 females (23.9%) and the age range was 16-94 years
      (mean+/-SD=39.26+/-19.00) and 16-93 years (mean+/-SD=63.36+/-23.46) for males and
      females, respectively. Fourteen out of the 46 fatal poisonings were suicide
      (30.4%), 30 (69.6%) were accident, and 2 were uncertain cases. Pesticides were
      the most common poisons used for suicide purposes (64.3% of suicides). Drugs of
      abuse were implicated in the majority of accidental poisoning deaths (73.3%) and
      were recorded mainly for males (95.5%). The selected cases were classified
      according to ICD-9 codes.

PMID- 17023193
TI  - Sudden death in a patient with idiopathic scoliosis.
AB  - We report an autopsy case of sudden death in a 36-year-old craftsman with
      idiopathic scoliosis. The doctor identified his scoliosis at the age of thirteen,
      and he was under medical care for three years until he stopped consulting the
      doctor. He collapsed while walking at the station and was sent to an emergency
      room in cardiopulmonary arrest state, where he was declared dead in spite of more
      than an hour of CPR. Numbers of petechiae were seen on the bilateral palpebral
      conjunctivae and the lips were cyanotic. There were no particular injuries except
      for small abrasions observed on the face. The back showed right rib hump owing to
      midthoracic scoliosis (with 73 degrees of Cobb's angle) and right hemithorax was
      deformed showing an appearance of pectus excavatum in the front. The volume of
      the right thoracic cavity was significantly decreased. In the right lung, there
      was extensive stromal fibrosis, leaving almost no normal alveolar structures, and
      medial hypertrophy of pulmonary arteriolar walls. Hypertrophy of the right heart
      ventricle due to these pulmonary changes and the congestion of other organs
      suggested that the cause of death in this case was cor pulmonale due to pulmonary
      hypertension. This was a rare case of fatal outcome of advanced idiopathic
      scoliosis without medical care in spite of early detection through mass
      screening.

PMID- 17023192
TI  - Homicide in Tours (Indre-et-Loire, France): a four-year review.
AB  - This retrospective study examined homicides in two French departments located in
      the West of France (Indre-et-Loire and Loir-et-Cher) for a four-year period from
      2000 to 2003. During this period 63 homicidal deaths were investigated at the
      Institute of Forensic Science of Tours (Indre-et-Loire). There were 45 male and
      18 female victims with an average homicide rate of 1.55 per 100,000 persons. The
      mean age of the victims was 42 years-old. Forty-five assailants were identified;
      their mean age was 38 years-old. The most common method of homicide was the use
      of firearms (40% of the cases), followed by blunt-force injury (36%) and sharp
      force injury (16%). 51% of the victims knew their assailant, a family member in
      26% of the cases. Spousal homicides occurred in 16% of the cases. Dyadic death
      occurred in six cases. A review of the literature compares these findings to
      other populations.

PMID- 17023194
TI  - Geometries and electronic structures of metastable C2N4 and its ions.
AB  - We carried out the computational studies on the geometric and electronic
      properties of electronic states of metastable C(2)N(4) (m-C(2)N(4)) and
      corresponding ions using the CASSCF and DFT(B3LYP)/CCSD(T) techniques. The
      optimized geometries of electronic states, vibrational frequencies, Mulliken
      populations, bond orders, and average polarizabilities are computed at the DFT
      level while the relative energies of the electronic states, ionization energy,
      electron affinity, binding energy of m-C(2)N(4) are calculated at the CCSD(T)
      level. The anion photoelectron spectra of m-C(2)N(4)(-) are also predicted. It is
      interesting to find that the relative energies of the electronic states of m
      C(2)N(4) cluster linearly correlate with the amount of charge transfer between N
      and C atoms and that, however, there is no charge transfer between C and N atoms
      upon electron ionization or electron attachment.

PMID- 17023195
TI  - Vibrational spectroscopic studies and ab initio calculations of 5-methyl-2-(p
      fluorophenyl)benzoxazole.
AB  - FT-Raman and FT-IR spectra of 5-methyl-2-(p-fluorophenyl)benzoxazole were
      recorded and analysed. The vibrational frequencies of the compound have been
      computed using the Hartree-Fock/6-31G* basis and compared with the experimental
      values.

PMID- 17023196
TI  - Reactivity trends of the base hydrolysis of coumarin and thiocoumarin in binary
      aqueous-methanol mixtures at different temperatures.
AB  - Rate constants for base hydrolysis of both coumarin and thiocoumarin have been
      studied in different binary aqueous-methanol mixtures at temperature range from
      288 to 313 K. The activation parameters of the reactions were evaluated.
      Moreover, the change in the activation barrier of the investigated compounds from
      water to water-methanol mixtures were estimated from the kinetic data.

PMID- 17023197
TI  - ESR and optical study of Mn2+ doped ammonium selenate single crystals.
AB  - ESR and optical absorption studies of manganese doped ammonium selenate single
      crystals are performed at X-band and room temperature to ascertain the site
      symmetry and location of impurity ions in the lattice. Manganese ions are
      expected to enter the lattice interstitially. Various spin Hamiltonian parameters
      are determined. Optical absorption study is also done and associated distortion
      in the crystal lattice is estimated.

PMID- 17023198
TI  - Lewis acid-base adducts: a quantitative Raman analysis of formamide and
      dimethylsulfoxide mixtures.
AB  - Raman spectra of pure liquid dimethylsulfoxide (DMSO) and of binary mixtures of
      formamide (FA) and DMSO in different compositions were obtained. The vibrations
      involving the SO functional group in the band envelope at ca. 1050 cm(-1) of pure
      liquid DMSO are assigned to monomers, dimers and higher aggregates of DMSO. The
      appearance of a new band at 1024 cm(-1), whose intensity shows large dependence
      on the FA concentration, is assigned to a FA-DMSO adduct. This has been possible
      due to the two H-bond donor sites of FA and the strong donor character of DMSO
      that become the environment propitious for the donor-acceptor reaction.
      Quantitative analysis performed in the SO stretching region in the binary
      mixtures gives a 1:1 stoichiometry in this adduct in the limit of infinite
      dilution. This proportion is in full agreement with our previous determination
      for the FA-ACN adduct. The experimental evidence of the 1:1 FA-DMSO adduct is
      presented for the first time using Raman spectroscopy. The results described here
      open new possibilities to study the acid-base reactions nature of FA adducts.

PMID- 17023199
TI  - Studies of the defect structure for Mn2+ in KTaO3 crystal from the calculation of
      EPR zero-field splitting.
AB  - There are several mistakes in the recent paper about the theoretical studies of
      defect structure for Mn(2+) ion at the 12-fold tetrakaidecahedral K+ site in
      KTaO(3) by calculating the spin Hamiltonian (SH) parameters, so the calculated
      defect structure (which is smaller than those obtained from the local density
      approximation (LDA) method, density functional theory in the generalized gradient
      approximation (GGA) and the dipole moment study (DMS)) is doubtful. Therefore, we
      restudy the defect structure in this paper by using the reasonable expressions
      and parameters. The present result is in agreement with those based on LDA, GGA
      and DMS methods and can be regarded as reasonable. It appears that the
      reliability of the defect structure of impurity center determined from the
      calculation of SH parameter depends strongly upon reasonableness of the used
      expressions and parameters.

PMID- 17023200
TI  - Vibrational spectroscopy of selected minerals of the rosasite group.
AB  - Minerals in the rosasite group namely rosasite, glaucosphaerite, kolwezite,
      mcguinnessite have been studied by a combination of infrared and Raman
      spectroscopy. The spectral patterns for the minerals rosasite, glaucosphaerite,
      kolwezite and mcguinnessite are similar to that of malachite implying the
      molecular structure is similar to malachite. A comparison is made with the
      spectrum of malachite. The rosasite mineral group is characterised by two OH
      stretching vibrations at approximately 3401 and 3311 cm-1. Two intense bands
      observed at approximately 1096 and 1046 cm-1 are assigned to nu1(CO3)2- symmetric
      stretching vibration and the delta OH deformation mode. Multiple bands are found
      in the 800-900 and 650-750 cm-1 regions attributed to the nu2 and nu4 bending
      modes confirming the symmetry reduction of the carbonate anion in the rosasite
      mineral group as C2v or Cs. A band at approximately 560 cm-1 is assigned to a CuO
      stretching mode.

PMID- 17023201
TI  - GALEN based formal representation of ICD10.
AB  - OBJECTIVES: The main objective is to create a knowledge-intensive coding support
      tool for the International Classification of Diseases (ICD10), which is based on
      formal representation of ICD10 categories. Beyond this task the resulting
      ontology could be reused in various ways. Decidability is an important issue for
      computer-assisted coding; consequently the ontology should be represented in
      description logic. METHODS: The meaning of the ICD10 categories is represented
      using the GALEN Core Reference Model. Due to the deficiencies of its
      representation language (GRAIL) the ontology is transformed to the quasi-standard
      OWL. A test system which extracts disease concepts and classifies them to ICD10
      categories has been implemented in Prolog to verify the feasibility of the
      approach. RESULTS: The formal representation of the first two chapters of ICD10
      (infectious diseases and neoplasms) has been almost completed. The constructed
      ontology has been converted to OWL DL. The test system successfully identified
      diseases in medical records from gastrointestinal oncology (84% recall, however
      precision is only 45%). The classifier module is still under development. Due to
      the experiences gained during the modelling, in the future work FMA is going to
      be used as anatomical reference ontology.

PMID- 17023202
TI  - Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4.
AB  - G protein coupled receptors (GPCRs) form homo- and hetero-dimers or -oligomers,
      which are functionally important. Lysophosphatidic acid (LPA) and sphingosine-1
      phosphate (S1P) are bioactive lysophopholipids involved in diverse biological
      processes. We have examined homo- and hetero-dimerization among three major LPA
      receptors (LPA(1-3)), three major S1P receptors (S1P(1-3)), as well as OGR1 and
      GPR4. Using LacZ complementation assays, we have shown that LPA receptors form
      homo- and hetero-dimers within the LPA receptor subgroup and hetero-dimers with
      other receptors (S1P(1-3) and GPR4). In addition, we have found that although
      GPR4 and OGR1 share more than 50% homology, GPR4 forms strong homo- and hetero
      dimers with LPA and S1P receptors, but OGR1 forms very weak homo-dimer and
      relatively weak hetero-dimers with other receptors. Using chimeric receptors
      between GPR4 and OGR1, we have shown that different domains of GPR4 receptor are
      involved in its dimerization with different GPCRs and more than one domain may be
      involved in some of the complex formation. Our results suggest that when studying
      a signal transduction induced by a stimulus, not only is the expression and
      activation of its own receptor(s), but also the status of the interacting
      receptors should be taken into consideration.

PMID- 17023203
TI  - Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients
      with chronic heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is associated with abnormalities of
      skeletal muscle metabolism. This may be due to impaired oxygen delivery as a
      result of endothelial dysfunction. AIMS: We postulated that ascorbic acid would
      improve oxygen delivery to exercising muscle and improve skeletal muscle
      metabolism. METHODS: We studied skeletal muscle metabolism using (31)P magnetic
      resonance spectroscopy in 39 CHF patients. Endothelial function was assessed by
      changes in pulse wave velocity. Subjects were randomised to receive 4 g ascorbic
      acid daily for 4 weeks in a placebo-controlled double-blind study. RESULTS:
      Ascorbic acid significantly increased phosphocreatine utilization during
      exercise. In addition, glycolytic ATP synthesis increased in the ascorbic acid
      group (change in rate of ATP synthesis at 1 min -0.21+/-0.76 with placebo, 2.06+/
      0.60 following ascorbic acid; p<0.05). Phosphocreatine and ADP recovery after
      exercise were not changed. The fall in pulse wave velocity during reactive
      hyperaemia was increased by ascorbic acid from -6.3+/-2.6% to -12.1+/-2.0%
      (p<0.05). CONCLUSIONS: These findings suggest that ascorbic acid increased both
      phosphocreatine utilization and glycolytic ATP synthesis during exercise in
      patients with CHF implying worsened skeletal muscle metabolism despite
      improvements in endothelial function.

PMID- 17023204
TI  - International variations in the treatment and co-morbidity of left ventricular
      systolic dysfunction: data from the EuroHeart Failure Survey.
AB  - BACKGROUND: Treatment of heart failure (HF) due to left ventricular systolic
      dysfunction (LVSD) is effective, but many patients are not treated in accordance
      with guidelines. This may reflect a lack of adequate organisation of care or co
      morbidity contra-indicating therapy. AIMS: To evaluate the effect of co
      morbidities on the prescription of neurohormonal antagonists for HF. METHODS AND
      RESULTS: The EuroHeart Failure Survey identified 10,701 patients with suspected
      or confirmed HF during 2000 and 2001, 64% of whom had an imaging test and 3658
      had documented LVSD. This last group constitutes the focus of this report. Renal
      dysfunction was associated with lower prescription of ACE inhibitors at discharge
      (74% vs. 83%, p<0.001). Beta-blockers were less often used in patients with
      respiratory disease (32% vs. 53%, p<0.001). Co-morbidity did not appear to affect
      the use of spironolactone. There were few important international differences in
      uptake of key therapies amongst European countries with widely differing cultures
      and economic status. CONCLUSIONS: Guidelines appear successful in creating a
      relatively uniform approach to the treatment for HF due to LVSD in diverse
      medical cultures. Relevant co-morbidity seems to be responsible for a substantial
      reduction in the prescription of ACE inhibitors and beta-blockers. However,
      whilst co-morbidity indicates the need for greater caution, it is often not a
      valid contra-indication to life-saving therapy.

PMID- 17023205
TI  - Recent changes in heart failure hospitalisations in Australia.
AB  - AIM: To assess trends in admissions of patients with heart failure (HF) to all
      hospitals in Australia between 1996-1997 and 2003-2004. METHODS AND RESULTS: We
      carried out a retrospective analysis of the official population-based National
      Hospital Morbidity Data in Australia. Although the absolute number of separations
      with a principal diagnosis of HF remained stable, the age- and sex-standardized
      separation rate for HF recorded as principal diagnosis decreased from 2.0 per
      1000 population in 1996-1997 to 1.6 per 1000 population in 2003-2004. The
      corresponding values for HF recorded in any diagnostic position were 7.7 and 4.7
      per 1000 population. Men had higher in-hospital mortality than women (8.9% versus
      8.1%, p<0.001) and also a larger decrease in this measure over the study period
      (21.9% versus 14.4%). While the geometric mean length of stay for HF as principal
      diagnosis fell from 5.4 days in 1996-1997 to 4.9 days in 2003-2004, the
      proportion of bed-days related to such diagnoses relative to total bed days
      attributed to circulatory diseases increased from 12.8% to 13.7% (p<0.001).
      CONCLUSION: There were no increase in number of admissions involving HF and
      standardized rates of hospital separations with HF fell in Australia between 1996
      and 2004. The explanation for the observed declines in in-hospital case fatality
      and the separation rates should be sought in whole-of-community studies.

PMID- 17023206
TI  - Changes in exercise capacity, ventilation, and body weight following heart
      transplantation.
AB  - AIMS: Peak oxygen uptake adjusted to body weight (peak VO(2)) and ventilatory
      efficiency (VE/VCO(2)-slope) are important prognostic parameters in chronic heart
      failure. Our study prospectively examined changes in these parameters over 24
      months following heart transplantation (HTx) and evaluated the potentially
      confounding effects of weight gain. METHODS AND RESULTS: One hundred patients
      with chronic heart failure (16 female, mean age at HTx 53.9+/-9.6 years)
      underwent cardiopulmonary exercise testing before and 3, 6, 12 and/or 24 months
      after HTx. Twenty-five healthy individuals served as matched normals. VE/VCO(2)
      slope during exercise improved significantly at 6 (-23.7%), 12 (-21.3%), and 24
      months (-32.3%; all p<0.002 vs. baseline). At 6 months, VE/VCO(2)-slopes were
      similar to the matched normals (31.8+/-4.3), 46 of 78 patients achieved values
      within the 95% confidence interval of normal. Peak VO(2) increased significantly
      after HTx at 6 (+31.8%), 12 (+36.2%), and 24 months (+42.2%; all p<0.005). None
      of the patients reached values within the 95% CI of normal. Although VE/VCO(2)
      slope and peak VO(2) were correlated inversely at every time point (p<0.03),
      reduction in VE/VCO(2)-slope did not correlate with increase in peak VO(2).
      Symptoms that limited exercise changed from dyspnoea before HTx to leg fatigue
      after HTx. CONCLUSION: Following HTX, VE/VCO(2)-slope returns to normal values in
      the majority of patients; however, despite improvement, peak VO(2) remains
      abnormal in all patients. Symptoms causing patients to stop exercising change
      from dyspnoea to leg fatigue.

PMID- 17023207
TI  - A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in
      patients with advanced heart failure.
AB  - BACKGROUND: The prognosis of chronic heart failure has improved with modern
      medical therapy. However, identifying those patients who fail to respond to such
      therapy and therefore those who remain at high risk is notoriously difficult. The
      B-type natriuretic peptides are established independent predictors of prognosis
      in CHF. However, the relevance of a change in NT-proBNP concentration over time
      in advanced heart failure is unknown. METHODS: We prospectively studied 133
      patients with advanced CHF referred for consideration of cardiac transplantation.
      Plasma for NT-proBNP analysis was sampled at baseline and a median of 4 months
      later in the 112 patients surviving without cardiac transplantation. Patients
      were followed up for a median of 1003 days. RESULTS: The primary endpoint of all
      cause mortality occurred in 30 (26.8%) patients. Those subjects who had the
      highest NT-proBNP concentration at 4 months were at the greatest risk of death
      (log rank statistic=10.4, p=0.001). On Cox regression analysis, both a NT-proBNP
      concentration above the median and an absolute increase in NT-proBNP were
      independent predictors of mortality (chi(2)=53, p<0.0001 and chi(2)=17.3,
      p<0.0001, respectively). CONCLUSION: A single NT-proBNP concentration above the
      median and a change in NT-proBNP concentration over a 4-month period were
      independent predictors of mortality in patients with advanced heart failure.

PMID- 17023208
TI  - Predictors of health-related quality of life in sufferers with restless legs
      syndrome: a multi-national study.
AB  - BACKGROUND AND PURPOSE: To explore aspects of restless legs syndrome (RLS)
      associated with detrimental impact on health-related quality of life (HRQoL).
      PATIENTS AND METHODS: The RLS epidemiology, symptoms, and treatment (REST) survey
      included SF-36 data on adults with RLS symptoms in the USA and five European
      countries. Linear regression models on each SF-36 dimension score explored
      factors influencing HRQoL in this population. RESULTS: Of 16,202 people surveyed,
      7% screened positively for RLS. Severity of RLS symptoms was strongly associated
      with impaired physical and mental HRQoL in both the cohorts from the USA and
      Europe. Distress and symptom frequency also had predictive capability. In
      addition, significantly diminished HRQoL was associated with the use of
      prescription medication for RLS symptoms. Age, number of comorbidities, and
      number of physician visits were statistically associated with lower HRQoL in
      respondents with RLS. CONCLUSIONS: Diminished HRQoL was partly accounted for by a
      number of RLS-related factors, including frequency, severity, and distress from
      symptoms. The negative impact of prescription medications on HRQoL, in contrast
      to demonstrated improvements with dopamine agonists, suggests inappropriate or
      ineffective medications are being used in this population. Our results strongly
      support the need for better physician education, both to diagnose the condition
      and importantly provide appropriate treatment with dopamine agonists, the only
      class of medication, that has been shown to improve the HRQoL of patients with
      RLS.

PMID- 17023209
TI  - Sleep cycling alternating pattern (CAP) expression is associated with hypersomnia
      and GH secretory pattern in Prader-Willi syndrome.
AB  - BACKGROUND AND PURPOSE: Hypersomnia, sleep-disordered breathing and narcoleptic
      traits such as rapid eye movement (REM) sleep onset periods (SOREMPs) have been
      reported in Prader-Willi syndrome (PWS). In a group of young adult patients with
      genetically confirmed PWS we evaluated sleep and breathing polysomnographically,
      including cycling alternating pattern (CAP), and we analyzed the potential
      interacting role of sleep variables, sleep-related breathing abnormalities,
      hypersomnia, severity of illness variables and growth hormone (GH) secretory
      pattern. PATIENTS AND METHODS: Eleven males and 7 females (mean age: 27.5+/-5.5
      years) were submitted to a full night of complete polysomnography and the
      multiple sleep latency test (MSLT). GH secretory pattern was evaluated by a
      standard GH-releasing hormone plus arginine test. Sixteen non-obese healthy
      subjects without sleep disturbances were recruited as controls. RESULTS: Compared
      to controls PWS patients showed reduced mean MSLT score (P<0.001), reduced mean
      latency of sleep (P=0.03), increased REM sleep periods (P=0.01), and increased
      mean CAP rate/non-rapid eye movement (NREM) (P<0.001). Only four PWS patients had
      apnea/hypopnea index (AHI)>or=10. Conversely, significant nocturnal oxygen
      desaturation was frequent (83% of patients) and independent from apneas or
      hypopneas. In the PWS group, CAP rate/NREM showed a significant negative
      correlation with MSLT score (P=0.02) independently from arousals, respiratory
      disturbance variables, severity of illness measured by Holm's score or body mass
      index (BMI). PWS patients with CAP expression characterized by higher proportion
      of A1 subtypes presented less severe GH deficiency (P=0.01). CONCLUSIONS: Our
      study suggests a relationship between hypersomnia and CAP rate, and between CAP
      expression and GH secretory pattern in PWS, possibly reflecting underlying
      central dysfunctions.

PMID- 17023210
TI  - Effects of CPAP on left ventricular structure and myocardial performance index in
      male patients with obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) has the potential to cause heart
      failure. We aimed to determine the effects of nasal continuous positive airway
      pressure (CPAP) therapy on left ventricular structure and myocardial performance
      index (MPI) in severe OSA patients. METHODS: Sixty-seven subjects without any
      cardiac or pulmonary disease had overnight polysomnography and echocardiography.
      In 33 males with severe OSA, thickness of interventricular septum (IVS) and
      posterior wall (LVPW) were measured by M-mode. Left ventricular MPI was
      calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic
      ejection time by Doppler. RESULTS: Eight males were non-compliant with CPAP. Mean
      age was 47.9+/-8.2 years, and 20 of 25 patients (80.0%) were hypertensive.
      Patients had high body mass index (BMI: 31.0+/-3.9 kg/m(2)), but there was no
      change in BMI from baseline after 6 months. Thickness of IVS (11.0+/-1.1mm) and
      LVPW (11.0+/-1.0mm) at baseline were significantly decreased after 6 months of
      CPAP therapy (10.5+/-0.9 mm, P<0.001 and 10.4+/-0.7 mm, P<0.0001, respectively).
      Left ventricular MPI (60.1+/-13.8%) significantly decreased (53.0+/-10.7%,
      P<0.0001) after CPAP usage. CONCLUSIONS: In male patients with severe OSA, CPAP
      therapy significantly decreases left ventricular wall thickness and improves
      global function even with 6 months of usage.

PMID- 17023211
TI  - Race and restless legs syndrome symptoms in an adult community sample in east
      Baltimore.
AB  - BACKGROUND & PURPOSE: Due to the relative absence of African-Americans seeking
      treatment for restless legs syndrome (RLS) in specialty clinics, a lower
      prevalence of RLS among African-Americans than Caucasians has been suggested. We
      compared the prevalence of RLS in African-Americans and Caucasians in a biracial
      community sample as part of Wave IV of the Baltimore Health and Mental Health
      Study. METHODS: Subjects included 1071 adults [358 African-Americans (35.0%), and
      633 Caucasians (61.8%), and 33 others]. Diagnosis of RLS was based on endorsement
      of RLS symptoms on a seven-item RLS questionnaire during a household interview.
      Adjusted odds and 95% confidence intervals were calculated based on logistic
      regression models with diagnosis of RLS as the main outcome variables and African
      American race as the main predictor while adjusting for other relevant
      sociodemographic and/or health-related variables. RESULTS: The prevalence of RLS
      in this population was 4.1%. The rates were similar for African-Americans (4.7%)
      and Caucasians (3.8%). After adjustment for age, gender, medical comorbidities,
      and socioeconomic status, no difference in the prevalence of RLS was found
      between African-Americans and Caucasians. CONCLUSION: RLS is comparably prevalent
      among African-American and Caucasian adults in the general population. Barriers
      affecting access to care settings for African-American RLS patients should be
      investigated in the future.

PMID- 17023212
TI  - Treatment of moderate obstructive sleep apnea syndrome with acupuncture: a
      randomised, placebo-controlled pilot trial.
AB  - BACKGROUND AND PURPOSE: To investigate the efficacy of acupuncture in the
      treatment of moderate obstructive sleep apnea syndrome (OSAS), assessed by
      polysomnography (PSG) and questionnaires of functional quality of life (SF-36)
      and excessive daytime sleepiness (Epworth). PATIENTS AND METHODS: We performed a
      randomised, placebo-controlled, single-blinded study, with blinded evaluation on
      36 patients presenting an apnea/hypopnea index (AHI) of 15-30/h, assessed by PSG.
      The study took place at the Public Hospital of the Universidade Federal de Sao
      Paulo, Brazil, in the Division of Sleep Disorders of the Department of
      Psychobiology, between January, 2002 and August, 2004. Patients were randomly
      assigned to three groups: the acupuncture group (n=12); the sham group, submitted
      to needle insertion in non-acupoints (n=12); and the control group, receiving no
      treatment (n=12). Patients received acupuncture or sham acupuncture once a week
      for 10 weeks. RESULTS: Twenty-six patients completed the study. The AHI
      (P=0.005), the apnea index (AI) (P=0.008) and the number of respiratory events
      (P=0.005) decreased significantly in the acupuncture group but not in the sham
      group. On the other hand, the control group displayed significant deterioration
      in some of the polysomnographic parameters, with a significant increase in the
      number of respiratory events (P=0.025). Acupuncture treatment significantly
      improved (before vs. after treatment) several dimensions of the SF-36 and Epworth
      questionnaires. There was no significant association between changes in the body
      mass index (BMI) and AHI. CONCLUSIONS: Acupuncture is more effective than sham
      acupuncture in ameliorating the respiratory events of patients presenting with
      moderate OSAS.

PMID- 17023213
TI  - Association of daytime napping and Parkinsonian signs in Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: Excessive daytime sleepiness (EDS) is reported in
      Alzheimer's disease (AD), with unstable sleep-wake rhythms that worsen with
      advancing disease stage. EDS is also very common in Parkinson's disease (PD),
      regardless of disease severity. The purpose of this study was to determine
      whether more Parkinsonian motor signs exist in AD patients with more reported
      daytime napping compared to AD patients without daytime napping. PATIENTS AND
      METHODS: AD patients ((National Institute of Neurological and Communicative
      Diseases and Stroke/Alzheimer's Disease and Related Disorders Association)
      NINCDS/ADRDA criteria) were prospectively evaluated in a dementia clinic.
      Parkinsonian motor signs were assessed using a modified motor Unified Parkinson's
      Disease Rating Scale (mmUPDRS). AD patients were grouped according to daytime
      napping frequency: (1) minimal napping (AD-Naps), or (2) napping at least once a
      day (AD+Naps). Wilcoxon rank-sum tests and chi2-tests computed differences
      between groups for mmUPDRS, nighttime sleep disturbances, and the Mini Mental
      State Examination (MMSE). Statistical significance was set at P<0.05. RESULTS: AD
      patients were classified as AD-Naps (n=155) or AD+Naps (n=180). Compared with AD
      Naps patients, AD+Naps patients had higher total mmUPDRS scores (P<0.001), higher
      rigidity scores (P<0.005), and more gait impairment (P<0.001). CONCLUSION: AD
      patients with more reported daytime napping had more Parkinsonian motor signs,
      suggesting that this subgroup may have an increased propensity for sleepiness
      resembling PD. Longitudinal studies with objective measures are needed to
      determine whether causal relationships exist between sleepiness and Parkinsonism
      in AD.

PMID- 17023214
TI  - Cell cycle-dependent expression of gamma-tubulin in the amicronuclear ciliate
      Tetrahymena pyriformis.
AB  - In ciliates, different microtubular structures are nucleated from diverse
      Microtubule Organizing Centers (MTOCs). gamma-Tubulin is a tubulin superfamily
      member that plays an essential role in microtubule nucleation at the MTOCs.
      However, little is known about mechanisms regulating the activity of gamma
      tubulin on different MTOCs and during the cell cycle. In Tetrahymena thermophila,
      the alpha- and beta-tubulin expression is regulated mainly at the transcriptional
      level, and changes in the ratio of polymerized/unpolymerized tubulin dimers lead
      to an increase or decrease of alpha- and beta-tubulin transcription. This study
      deals with the characterization of gamma-tubulin in the amicronuclear ciliate
      Tetrahymena pyriformis. Sequence analysis revealed some specific substitutions in
      nucleotide-binding loops characteristic of the Tetrahymena genus and putative
      conserved phosphorylation sites located on the external surface of the gamma
      tubulin molecule. gamma-Tubulin expression during the cell cycle, in the presence
      of microtubular poisons and after deciliation, was also characterized. We found
      that gamma-tubulin mRNA levels are correlated with basal body proliferation and
      gamma-tubulin nuclear localization. We also found that gamma-tubulin expression
      changes during anti-microtubular drugs treatment, but does not changes during
      reciliation. These findings suggest a relationship between the level of
      unpolymerized tubulin dimers and gamma-tubulin transcription.

PMID- 17023215
TI  - Leishmaniasis and poverty.
AB  - Leishmaniasis, a neglected tropical disease, has strong but complex links with
      poverty. The burden of leishmaniasis falls disproportionately on the poorest
      segments of the global population. Within endemic areas, increased infection risk
      is mediated through poor housing conditions and environmental sanitation, lack of
      personal protective measures and economically driven migration and employment
      that bring nonimmune hosts into contact with infected sand flies. Poverty is
      associated with poor nutrition and other infectious diseases, which increase the
      risk that a person (once infected) will progress to the clinically manifested
      disease. Lack of healthcare access causes delays in appropriate diagnosis and
      treatment and accentuates leishmaniasis morbidity and mortality, particularly in
      women. Leishmaniasis diagnosis and treatment are expensive and families must sell
      assets and take loans to pay for care, leading to further impoverishment and
      reinforcement of the vicious cycle of disease and poverty. Public investment in
      treatment and control would decrease the leishmaniasis disease burden and help to
      alleviate poverty.

PMID- 17023216
TI  - Polymorphisms of interferon-gamma and interferon-gamma receptor 1 genes and non
      tuberculous mycobacterial lung diseases.
AB  - Interferon-gamma (IFN-gamma) is crucial for host defense against mycobacterial
      infections. Recent studies have indicated that IFN-gamma and IFN-gamma receptor 1
      (IFN-gammaR1) gene polymorphisms are associated with susceptibility to pulmonary
      tuberculosis. The aim of this study was to test the hypothesis that IFN-gamma and
      IFN-gammaR1 gene polymorphisms influence susceptibility to lung disease caused by
      non-tuberculous mycobacteria (NTM). Seventy-six patients with the nodular
      bronchiectatic form of NTM lung disease (37 patients with Mycobacterium avium
      complex infection and 39 patients with Mycobacterium abscessus infection) and 80
      controls were included. Polymorphisms of the IFN-gamma gene at position +874 were
      determined by the amplification refractory mutation system (ARMS) polymerase
      chain reaction assay and IFN-gammaR1 gene at positions -611, -270, -56 and +95
      was genotyped by matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry using genomic DNA. IFN-gammaR1 -270 and +95
      polymorphisms were not present in any of the patients or controls. The patients
      with NTM lung disease showed no significant difference from controls in genotype
      and allele frequencies of the IFN-gamma +874 and IFN-gammaR1 -611 and -56
      polymorphisms. The IFN-gamma +874 and IFN-gammaR1 -611 and -56 polymorphisms do
      not appear to be responsible for host susceptibility to NTM lung disease, at
      least in the Korean population.

PMID- 17023217
TI  - A novel fusion protein-based indirect enzyme-linked immunosorbent assay for the
      detection of bovine tuberculosis.
AB  - Enzyme-linked immunosorbent assay (ELISA) for diagnosis of bovine tuberculosis
      has been widely explored over the years. Three Mycobacterium bovis-specific
      antigen genes, namely, mpb70, mpb83, and esat-6 were recombined in tandem by
      spliced overlap extension technology and expressed in Escherichia coli to obtain
      the fusion protein (rM70-83-E6). Western blot analysis showed that rM70-83-E6 can
      specifically react with bovine tuberculosis-positive sera but not those from
      cattle infected with other bovine diseases such as bovine paratuberculosis. An
      indirect ELISA (iELISA) method was established with rM70-83-E6 as the diagnostic
      antigen. The diagnostic criteria were determined using 150 serum samples from
      healthy cattle. Analyses of 85 serum samples from cattle with bovine tuberculosis
      and 100 serum samples from healthy cattle demonstrated that the sensitivity of
      the iELISA was 69.4% (59/85) and the specificity was 96.0% (96/100). Moreover, 46
      out of 67 purified protein derivative (PPD) skin test-positive samples were also
      positive by iELISA, giving a positive coincidence of 68.7%, while all 50 PPD skin
      test-negative samples were negative by iELISA, giving a negative coincidence of
      100%. The total coincidence between iELISA and the PPD skin test was 82.1%. This
      study demonstrated that iELISA using rM70-83-E6 antigen is simple, sensitive and
      easy to perform and can be used to analysis of a large number of samples for
      serodiagnosis of bovine tubercuiosis.

PMID- 17023218
TI  - Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with
      positron emission tomography: a pilot study.
AB  - Although the pathophysiology underlying the pain of fibromyalgia syndrome (FMS)
      remains unknown, a variety of clinical and investigational findings suggests a
      dysregulation of dopaminergic neurotransmission. We therefore investigated
      presynaptic dopaminergic function in 6 female FMS patients in comparison to 8 age
      and gender-matched controls as assessed by positron emission tomography with 6
      [(18)F]fluoro-L-DOPA as a tracer. Semiquantitative analysis revealed reductions
      in 6-[(18)F]fluoro-L-DOPA uptake in several brain regions, indicating a
      disruption of presynaptic dopamine activity wherein dopamine plays a putative
      role in natural analgesia. Although the small sample size makes these findings
      preliminary, it appears that FMS might be characterized by a disruption of
      dopaminergic neurotransmission. PERSPECTIVE: An association between FMS and
      reduced dopamine metabolism within the pain neuromatrix provides important
      insights into the pathophysiology of this mysterious disorder.

PMID- 17023219
TI  - The long pentraxin PTX3 in vascular pathology.
AB  - Pentraxins are a family of evolutionarily conserved multifunctional pattern
      recognition proteins characterized by a cyclic multimeric structure. Based on the
      primary structure of the subunit, the pentraxins are divided into two groups:
      short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid
      P-component (SAP) are the two short pentraxins. The prototype protein of the long
      pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the
      liver in response to IL-6, while PTX3 is produced by a variety of tissues and
      cells and in particular by innate immunity cells in response to proinflammatory
      signals and Toll-like receptor (TLR) engagement. PTX3 interacts with several
      ligands, including growth factors, extracellular matrix components and selected
      pathogens, playing a role in complement activation and facilitating pathogen
      recognition by phagocytes, acting as a predecessor of antibodies. In addition,
      PTX3 is essential in female fertility by acting as a nodal point for the assembly
      of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the
      prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition
      receptor acting as a non-redundant component of the humoral arm of innate
      immunity and involved in tuning inflammation, in matrix deposition and female
      fertility.

PMID- 17023220
TI  - Comparison of outcomes after laparoscopic adjustable gastric banding in African
      Americans and whites.
AB  - BACKGROUND: Race may affect outcomes after bariatric surgery. This study compares
      outcomes in terms of weight loss and comorbidity resolution between African
      Americans and whites after laparoscopic adjustable gastric banding (LAGB).
      METHODS: Data from 959 patients undergoing LAGB between July 2001 and July 2004
      were prospectively collected and entered into an electronic registry. Propensity
      score matching analysis was used to match whites to African-Americans on the
      basis of age, gender, and preoperative body mass index (BMI). Preoperative
      comorbidities (diabetes, hypertension, obstructive sleep apnea,
      hypercholesterolemia, and hypertriglyceridemia) were also compared. Operative
      time (OR), length of stay (LOS), comorbidity resolution, and percent excess
      weight loss (%EWL) at 1, 2, and 3 years were analyzed. All data were updated
      through May 2006. RESULTS: A total of 65 white LAGB patients were matched to 58
      African-American LAGB patients on the basis of age, gender, and preoperative BMI.
      The preoperative mean age and BMI were 37 +/- 19 years and 47 +/- 7 kg/m2,
      respectively. A total of 55% of the white group and 64% of the African-American
      group had one or more comorbidities (P = NS). Median OR time and LOS were similar
      in both groups: 50 minutes and 23 hours, respectively. The majority of patients
      in both groups had major improvement or resolution of one or more comorbidities
      (61% whites vs 77% African-Americans, P = NS). There was, however, a significant
      difference in %EWL between whites and African-Americans at each time interval
      (49% vs 39% at 1 year; 55% vs 44% at 2 years; 52% vs 41% at 3 years; P < .05 for
      all values.). CONCLUSION: Despite the disparity in weight loss with the LAGB in
      African-Americans and whites, both patient populations experienced a similar
      improvement/resolution of obesity-related comorbidities.

PMID- 17023221
TI  - Stimulation of intestinal secretion by vasoactive intestinal peptide and cholera
      toxin.

PMID- 17023222
TI  - Global and targeted quantitative proteomics for biomarker discovery.
AB  - The extraordinary developments made in proteomic technologies in the past decade
      have enabled investigators to consider designing studies to search for diagnostic
      and therapeutic biomarkers by scanning complex proteome samples using unbiased
      methods. The major technology driving these studies is mass spectrometry (MS).
      The basic premises of most biomarker discovery studies is to use the high data
      gathering capabilities of MS to compare biological samples obtained from healthy
      and disease-afflicted patients and identify proteins that are differentially
      abundant between the two specimen. To meet the need to compare the abundance of
      proteins in different samples, a number of quantitative approaches have been
      developed. In this article, many of these will be described with an emphasis on
      their advantageous and disadvantageous for the discovery of clinically useful
      biomarkers.

PMID- 17023223
TI  - Automated solid-phase extraction for the determination of polybrominated diphenyl
      ethers and polychlorinated biphenyls in serum--application on archived Norwegian
      samples from 1977 to 2003.
AB  - An analytical method comprised of automated solid-phase extraction and
      determination using gas chromatography mass spectrometry (single quadrupole) has
      been developed for the determination of 12 polybrominated diphenyl ethers
      (PBDEs), 26 polychlorinated biphenyls (PCBs), two organochlorine compounds (OCs)
      (hexachlorobenzene and octachlorostyrene) and two brominated phenols
      (pentabromophenol, and tetrabromobisphenol-A (TBBP-A)). The analytes were
      extracted using a sorbent of polystyrene-divinylbenzene and an additional clean
      up was performed on a sulphuric acid-silica column to remove lipids. The method
      has been validated by spiking horse serum at five levels. The mean accuracy given
      as recovery relative to internal standards was 95%, 99%, 93% and 109% for the
      PBDEs PCBs, OCs and brominated phenols, respectively. The mean repeatability
      given as RSDs was respectively 6.9%, 8.7%, 7.5% and 15%. Estimated limits of
      detection (S/N=3) were in the range 0.2-1.8 pg/g serum for the PBDEs and phenols,
      and from 0.1 pg/g to 56 pg/g serum for the PCBs and OCs. The validated method has
      been used to investigate the levels of PBDEs and PCBs in 21 pooled serum samples
      from the general Norwegian population. In serum from men (age 40-50 years) the
      sum of seven PBDE congeners (IUPAC No. 28, 47, 99, 100, 153, 154 and 183)
      increased from 1977 (0.5 ng/g lipids) to 1998 (4.8 ng/g lipids). From 1999 to
      2003 the concentration of PBDEs seems to have stabilised. On the other hand, the
      sum of five PCBs (IUPAC No. 101, 118, 138, 153 and 180) in these samples
      decreased steadily from 1977 (666 ng/g lipids) to 2003 (176 ng/g lipids).
      Tetrabromobisphenol-A and BDE-209 were detected in almost all samples, but no
      similar temporal trends to that seen for the PBDEs were observed for these
      compounds, which might be due to the short half-lives of these brominated flame
      retardants (FR) in humans.

PMID- 17023224
TI  - Development and validation of a capillary electrophoresis method for the
      characterization of herpes simplex virus type 1 (HSV-1) thymidine kinase
      substrates and inhibitors.
AB  - A fast, convenient capillary electrophoresis (CE) method was developed for
      monitoring the enzymatic reaction of herpes simplex virus type 1 thymidine kinase
      (HSV-1 TK). The reaction was performed in a test tube followed by quantitative
      analysis of the products. The optimized CE conditions were as follows:
      polyacrylamide-coated capillary (20 cm effective length x 50 microm),
      electrokinetic injection for 30s, 50 mM phosphate buffer at pH 6.5, constant
      current of -60 microA, UV detection at 210 nm, UMP or cAMP were used as internal
      standards. Phosphorylated products eluted within less than 7 min. The limits of
      detection were 0.36 microM for dTMP and 0.86 microM for GMP. The method was used
      to study enzyme kinetics, and to investigate alternative substrates and
      inhibitors.

PMID- 17023225
TI  - Estrogen and androgen play distinct roles in bone turnover in male mice before
      and after reaching sexual maturity.

PMID- 17023226
TI  - Design of a novel controlled-release formulation of carvedilol: pharmacology and
      clinical aspects. Introduction.

PMID- 17023227
TI  - Pharmacokinetic properties of a new controlled-release formulation of carvedilol.
AB  - This review summarizes the pharmacokinetics (PK) of carvedilol after
      administration of a new once-daily controlled-release (CR) formulation. The
      plasma concentration-time profiles for both R(+)- and S(-)-carvedilol indicate
      that carvedilol CR will provide coverage over a 24-hour period similar to the
      current immediate-release (IR) twice-daily formulation. Exposures for both
      enantiomers, based on area under the curve (AUC), maximum plasma concentrations
      (C(max)), and trough concentrations, are equivalent for carvedilol CR compared
      with carvedilol IR. C(max) and AUC of the enantiomers of carvedilol increase in
      an approximate dose-proportional manner after administration of carvedilol CR
      over the dose range of 10-80 mg, indicating that the formulation provides
      consistent PK performance across the dose strengths proposed for marketing. The
      intrasubject and intersubject variability of carvedilol CR was comparable to
      carvedilol IR. For carvedilol CR, mean AUC and C(max) were increased <20% after a
      high-fat meal compared with a standard meal. The CR and IR formulations of
      carvedilol exhibited equivalent steady-state PK characteristics in the target
      hypertension and heart failure populations. The availability of once-daily dosing
      is expected to improve treatment adherence and thereby enhance the effectiveness
      of carvedilol in routine clinical use.

PMID- 17023228
TI  - Pharmacokinetic and pharmacodynamic comparison of controlled-release carvedilol
      and immediate-release carvedilol at steady state in patients with hypertension.
AB  - Carvedilol is indicated for the treatment of essential hypertension and mild-to
      severe chronic heart failure, as well as the reduction of cardiovascular
      mortality in clinically stable post-myocardial infarction patients with left
      ventricular dysfunction. Carvedilol is a racemic mixture of R(+) and S(-)
      enantiomers that combines beta(1)-, beta(2)-, and alpha(1)-adrenoceptor blockade.
      For all indications, the immediate-release (IR) formulation of carvedilol is
      taken twice daily. A controlled-release (CR) formulation of carvedilol that
      allows once-daily dosing has recently been developed. In this double-blind,
      parallel-group, crossover study, 122 patients with essential hypertension were
      randomly allocated to receive low and high doses of carvedilol or placebo.
      Patients received either a constant low dose (CR 20 mg once daily or IR 6.25 mg
      twice daily) or were titrated to a high dose (CR 80 mg once daily or IR 25 mg
      twice daily) before being crossed over to an equivalent dose of the alternative
      formulation. The pharmacokinetic (PK) and pharmacodynamic (PD) profiles were
      compared between patients receiving carvedilol CR and carvedilol IR. The PK
      profiles for R(+)- and S(-)-carvedilol for the 2 formulations were equivalent
      (based on area under the curve, maximum plasma concentration [C(max)], and trough
      drug concentration). Consistent with an extended-release formulation, carvedilol
      CR delayed C(max) by 3.5 hours compared with carvedilol IR. For both carvedilol
      CR and IR, the attenuation of exercise-induced heart rate in patients with
      hypertension was maintained over the entire 24-hour period, and the 2
      formulations demonstrated equivalent beta(1)-blocking effects at trough (end of
      the dosing interval [PD(min)]), suggesting that the rate of absorption does not
      interfere with the PD effect. In this first direct comparison of carvedilol CR
      and IR in subjects with hypertension, fewer adverse events were reported while
      subjects were receiving carvedilol CR (59.1% overall) compared with carvedilol IR
      (77.5% overall). This was true regardless of dose received. Headache was the most
      commonly reported adverse event for subjects receiving either formulation of
      carvedilol and placebo. Importantly, dizziness and headache were reported less
      often when subjects received carvedilol CR. This is the first study to show that
      both formulations had comparable beta(1)-adrenergic blockade in patients with
      essential hypertension under steady-state conditions. Notably, carvedilol CR
      provides consistent beta(1)-adrenergic blockade over 24 hours with a once-daily
      dose.

PMID- 17023229
TI  - Development of a pharmacokinetic/pharmacodynamic model for carvedilol to predict
      beta1-blockade in patients with congestive heart failure.
AB  - To determine whether the controlled-release (CR) formulation of carvedilol given
      once daily provides 24-hour beta1-receptor blockade similar to the currently
      marketed immediate-release (IR) formulation given twice daily, changes in
      exercise-induced heart rate after bicycle ergometry were measured. The
      pharmacokinetic (PK)/pharmacodynamic (PD) relation between S(-)-carvedilol
      concentration-the enantiomer with beta-blocking activity-and change in exercise
      induced heart rate was defined in healthy subjects and was best described using a
      direct effect inhibitory E(max) model (with E(max) being the maximum effect). The
      population estimates for E(max) and concentration at 50% of the maximum effect
      (EC50) were 19.2 beats per minute (an approximately 13% maximum decrease in
      exercise-induced heart rate) and 7.7 ng/mL, respectively. The PK/PD model was
      used to predict PD effects in patients with mild-to-severe heart failure and in
      patients after myocardial infarction with left ventricular dysfunction who had
      received both the IR and CR formulations of carvedilol. In these patients,
      carvedilol CR had equivalent predicted overall PD (area under the effect curve)
      and trough (PD(min)) effects compared with carvedilol IR, indicating 24-hour beta
      blocking coverage for the new CR formulation of carvedilol given once daily.

PMID- 17023230
TI  - Controlled-release carvedilol in the treatment of essential hypertension.
AB  - Carvedilol is a beta1-, beta2-, and alpha1-adrenergic blocker that is approved
      for the treatment of hypertension. A new once-daily, controlled-release (CR)
      formulation of carvedilol has been shown to be effective in a double-blind,
      randomized, multicenter, placebo-controlled, parallel-group study. In this
      article, we summarize the primary results of, and present additional analyses
      from, that trial. A total of 338 patients with essential hypertension (sitting
      diastolic blood pressure [DBP] >/=90 and </=109 mm Hg) were randomized to receive
      carvedilol CR 20, 40, or 80 mg or placebo for 6 weeks. The primary objective was
      to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean
      blood pressure using ambulatory blood pressure monitoring (ABPM). Mean DBP and
      systolic BP (SBP) at the drug trough (20-24 hour) blood levels for carvedilol CR
      and comparison of DBP and SBP at the drug peak (3-7 hour) blood levels for each
      dose of carvedilol CR and placebo were investigated. The effects of carvedilol CR
      on heart rate and pulse pressure were also examined. Once-daily administration of
      carvedilol CR, alone or in combination with other agents, produced clinically and
      statistically significant reductions compared with placebo for both DBP and SBP
      after 6 weeks of treatment for the following parameters: trough blood pressure by
      office cuff or ABPM measurements, peak blood pressure by ABPM, and 24-hour mean
      blood pressure by ABPM. Placebo-corrected trough-to-peak ratios for DBP were >0.6
      for each carvedilol CR dose. Heart rate and pulse pressure were each
      significantly reduced compared with placebo for each carvedilol CR dose. We
      conclude that carvedilol CR is a very effective antihypertensive agent with clear
      dose-related peak blood pressure reduction and continuous 24-hour control.

PMID- 17023231
TI  - Pharmacokinetic profile of controlled-release carvedilol in patients with left
      ventricular dysfunction associated with chronic heart failure or after myocardial
      infarction.
AB  - We compared the pharmacokinetic (PK) profiles of repeated dosing with the
      currently available immediate-release (IR) carvedilol (given twice daily) and a
      newly developed controlled-release (CR) formulation (given once daily) in
      patients with left ventricular dysfunction (LVD). We enrolled 188 patients with
      stable mild, moderate, or severe heart failure as well as survivors of a recent
      acute myocardial infarction (MI) with asymptomatic LVD (left ventricular ejection
      fraction </=0.40) in a crossover study. PK variables were initially assessed
      after patients had received carvedilol IR 3.125, 6.25, 12.5, or 25 mg twice daily
      for >/=2 weeks. Patients were then switched to the corresponding dose of
      carvedilol CR (10, 20, 40, or 80 mg once daily), and PK variables were reassessed
      after an additional 2 weeks. The primary measures included trough plasma
      concentration (C(tau)), maximum plasma concentration (C(max)), and area under the
      concentration-time curve (AUC([0-t])) for both enantiomers of carvedilol of each
      formulation of the drug. The AUC((0-t)) and the trough and maximum carvedilol
      concentrations for both the R(+) and S(-) enantiomers were similar when
      carvedilol IR was compared with carvedilol CR as follows: 3.125 mg twice daily
      versus 10 mg once daily, 6.25 mg twice daily versus 20 mg once daily, 12.5 mg
      twice daily versus 40 mg once daily, and 25 mg twice daily versus 80 mg once
      daily, respectively. Based on a pooled analysis, the AUC((0-t)), C(max), and
      C(tau) for both R(+) and S(-) were equivalent for the CR and IR formulations,
      with point estimates and 90% confidence intervals within the bioequivalence
      limits of 80%-125%. The fluctuation index (the CR-IR ratio for [C(max) -
      C(min)]/C(ss) where C(min) is the minimum observed concentration over the dosing
      interval and C(ss) is the concentration at steady state) for both R(+)- and S(-)
      carvedilol was approximately 1, indicating that the peak-to-trough fluctuation in
      plasma concentration for carvedilol after use of carvedilol CR once daily was
      similar to that for carvedilol IR given twice daily. The median time to maximum
      observed plasma concentration (t(max)) was approximately 3 hours longer for both
      enantiomers after administration of carvedilol CR as compared with carvedilol IR.
      These data demonstrate that the new carvedilol CR formulation given once daily is
      equivalent to the currently available carvedilol IR formulation given twice daily
      in patients with heart failure and asymptomatic post-MI LVD.

PMID- 17023232
TI  - Cardiovascular risk factors in hypertension: rationale and design of studies to
      investigate the effects of controlled-release carvedilol on regression of left
      ventricular hypertrophy and lipid profile.
AB  - Patients at high risk for hypertension may require several therapeutic agents to
      lower their blood pressure to guideline-recommended targets. Some
      antihypertensive agents are more effective than others in protecting against
      cardiovascular morbidity and mortality. Numerous beta-blocking agents have been
      approved by the US Food and Drug Administration (FDA) for the treatment of
      hypertension. Previous trials have demonstrated that although all beta-blockers
      effectively reduce blood pressure, there are differences in how they affect
      various metabolic factors. In 2 trials, a novel controlled-release (CR)
      formulation of carvedilol will be tested against other selective beta-blockers to
      determine whether differences exist in their individual effects on cardiovascular
      risk factors. These will be the first head-to-head trials using carvedilol CR to
      determine whether the differing pharmacologic actions among beta-blockers result
      in varying effects on cardiovascular risk factors.

PMID- 17023233
TI  - COMPARE: comparison of the effects of carvedilol CR and carvedilol IR on left
      ventricular ejection fraction in patients with heart failure.
AB  - Left ventricular ejection fraction (LVEF) is an important measure of ventricular
      function in the evaluation of heart failure. Immediate-release (IR) carvedilol
      twice daily has been shown to improve LVEF in subjects with ischemic and
      nonischemic chronic heart failure. A once-daily formulation, controlled-release
      (CR) carvedilol, is expected to improve quality of care through improved
      adherence as a result of the reduced frequency of dosing. This multicenter,
      randomized, double-blind study in subjects with stable chronic heart failure will
      compare the change in LVEF in patients receiving carvedilol IR with those
      receiving carvedilol CR. LVEF will be measured by 2-dimensional echocardiography
      at 6 months after entry into the maintenance period of the study drug. The
      secondary objectives of this study are to assess changes in left ventricular
      remodeling and function, to evaluate changes in brain natriuretic peptide levels,
      and to determine the incidence of all-cause and heart failure-related
      hospitalizations and all-cause mortality after treatment with carvedilol CR or
      carvedilol IR.

PMID- 17023234
TI  - Rationale and design of CASPER: compliance and quality of life study comparing
      once-daily carvedilol CR and twice-daily carvedilol IR in patients with heart
      failure.
AB  - Adherence to a complex medical regimen in patients with chronic heart failure is
      an important problem. In the Medicare population, patients with heart failure
      take an average of 7-8 distinct medications that require >11 separate doses on a
      daily basis. Nonadherence to these regimens accounts for a significant proportion
      of hospital admissions. Simplification of the medical regimen for patients with
      heart failure is likely to be associated with improved adherence and, in
      parallel, may lead to greater satisfaction and potentially improved outcomes.
      Therefore, the Compliance and Quality of Life Study Comparing Once-Daily
      Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR
      in Patients with Heart Failure (CASPER) trial has been designed to rigorously
      test the hypothesis that a once-daily formulation of carvedilol will result in
      better compliance and increased patient satisfaction relative to the twice-daily
      formulation. The background, methods, and statistical approaches used in this
      trial are reviewed in this article.

PMID- 17023235
TI  - Controlled-release carvedilol: a concluding perspective.

PMID- 17023236
TI  - A natural setting behavior management program for persons with acquired brain
      injury: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the efficacy of a behavior management program delivered
      in the natural community setting for persons with brain injury and their
      caregivers. DESIGN: Three-group randomized controlled trial. SETTING: Homes and
      other community settings. PARTICIPANTS: Thirty-seven persons with traumatic and
      other acquired brain injury and their caregivers. INTERVENTIONS: Natural Setting
      Behavior Management (NSBM) involving education and individualized behavior
      modification program versus education only versus control group. MAIN OUTCOME
      MEASURES: Changes in frequency of targeted problematic behaviors. Subscale in
      Questionnaire on Resources and Stress, Maslach Burnout Inventory, and the
      Neurobehavioral Functioning Inventory. RESULTS: While no significant effects were
      detected at termination of education only (P<.075) or of NSBM (P<.56),
      significant treatment effects were found at the main outcome point 3 months after
      termination of services (P<.002). Rates of disruptive or aggressive behaviors
      declined significantly in the NSBM group. Differences in caregiver-rated stress,
      burden, and aggression were not statistically significant. CONCLUSIONS: A program
      of caregiver education and individualized behavior management in natural settings
      can decrease the frequency of disruptive behavioral challenges. Larger studies
      are needed to clarify the duration and intensity of education and individualized
      treatment required to diminish behavioral challenges and to understand
      relationships with general stress and burden experienced by caregivers.

PMID- 17023237
TI  - Effectiveness of gait training using an electromechanical gait trainer, with and
      without functional electric stimulation, in subacute stroke: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the therapeutic effects of conventional gait training
      (CGT), gait training using an electromechanical gait trainer (EGT), and gait
      training using an electromechanical gait trainer with functional electric
      stimulation (EGT-FES) in people with subacute stroke. DESIGN: Nonblinded
      randomized controlled trial. SETTING: Rehabilitation hospital for adults.
      PARTICIPANTS: Fifty patients were recruited within 6 weeks after stroke onset; 46
      of these completed the 4-week training period. INTERVENTION: Participants were
      randomly assigned to 1 of 3 gait intervention groups: CGT, EGT, or EGT-FES. The
      experimental intervention was a 20-minute session per day, 5 days a week
      (weekdays) for 4 weeks. In addition, all participants received their 40-minute
      sessions of regular physical therapy every weekday as part of their treatment by
      the hospital. MAIN OUTCOME MEASURES: Five-meter walking speed test, Elderly
      Mobility Scale (EMS), Berg Balance Scale, Functional Ambulatory Category (FAC),
      Motricity Index leg subscale, FIM instrument score, and Barthel Index. RESULTS:
      The EGT and EGT-FES groups had statistically significantly more improvement than
      the CGT group in the 5-m walking speed test (CGT vs EGT, P=.011; CGT vs EGT-FES,
      P=.001), Motricity Index (CGT vs EGT-FES, P=.011), EMS (CGT vs EGT, P=.006; CGT
      vs EGT-FES, P=.009), and FAC (CGT vs EGT, P=.005; CGT vs EGT-FES, P=.002) after
      the 4 weeks of training. No statistically significant differences were found
      between the EGT and EGT-FES groups in all outcome measures. CONCLUSIONS: In this
      sample with subacute stroke, participants who trained on the electromechanical
      gait trainer with body-weight support, with or without FES, had a faster gait,
      better mobility, and improvement in functional ambulation than participants who
      underwent conventional gait training. Future studies with assessor blinding and
      larger sample sizes are warranted.

PMID- 17023239
TI  - Continuous low-level heat wrap therapy for the prevention and early phase
      treatment of delayed-onset muscle soreness of the low back: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects of continuous low-level heat wrap therapy for
      the prevention and early phase treatment (ie, 0-48 h postexercise) of delayed
      onset muscle soreness (DOMS) of the low back. DESIGN: Two prospective randomized
      controlled trials. SETTING: Outpatient medical facility. PARTICIPANTS: Sixty
      seven subjects asymptomatic of back pain and in good general health (mean age,
      23.5+/-6.6 y). INTERVENTIONS: Participants performed vigorous eccentric exercise
      to experimentally induce low back DOMS. Participants were assigned to 1 of 2
      substudies (prevention and treatment) and randomized to 1 of 2 treatment groups
      within each substudy: prevention study (heat wrap, n=17; control [nontarget
      muscle stretch], n=18) and treatment study (heat wrap, n=16; cold pack, n=16).
      Interventions were administered 4 hours before and 4 hours after exercise in the
      prevention study and between hours 18 to 42 postexercise in the treatment study.
      MAIN OUTCOME MEASURES: To coincide with the expected occurrence of peak symptoms
      related to exercise-induced low back DOMS, hour 24 postexercise was considered
      primary. Pain intensity (prevention) and pain relief (treatment) were primary
      measures, and self-reported physical function and disability were secondary
      measures. RESULTS: In the prevention study, at hour 24 postexercise, pain
      intensity, disability, and deficits in self-reported physical function in
      subjects with the heat wrap were reduced by 47% (P<.001), 52.3% (P=.029), and 45%
      (P=.013), respectively, compared with the control group. At hour 24 in the
      treatment study, postexercise, pain relief with the heat wrap was 138% greater
      (P=.026) than with the cold pack; there were no differences between the groups in
      changes in self-reported physical function and disability. CONCLUSIONS: In this
      small study, continuous low-level heat wrap therapy was of significant benefit in
      the prevention and early phase treatment of low back DOMS.

PMID- 17023238
TI  - Prevalence and natural history of colonization with fluoroquinolone-resistant
      gram-negative bacilli in community-dwelling people with spinal cord dysfunction.
AB  - OBJECTIVES: To estimate the prevalence of colonization with fluoroquinolone
      resistant gram-negative bacilli (GNB) and to assess risk factors for and define
      the natural history of colonization. DESIGN: Cross-sectional study with follow-up
      of up to 1 year. SETTING: Multiple outpatient sites. PARTICIPANTS: Eighty-four
      community-dwelling adults with spinal cord dysfunction. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: Colonization of perineum with fluoroquinolone
      resistant GNB. RESULTS: Overall, 24% of this community-dwelling cohort was
      colonized with fluoroquinolone-resistant GNB with resistance to both levofloxacin
      and gatifloxacin. The use of any antibiotic in the last 90 days was most strongly
      associated with an increased risk of colonization with fluoroquinolone-resistant
      GNB (relative risk, 2.3; 95% confidence interval, 1.1-4.8; P=.05). Incontinence
      was significantly more common among those with fluoroquinolone-resistant GNB
      colonization. Among the participants with incontinence (n=42), the use of
      intermittent catheterization (vs suprapubic, urethral, or condom catheters or
      overflow incontinence) was significantly protective. Colonization was not
      associated with an increase in urinary tract infection and was often transient.
      CONCLUSIONS: Fluoroquinolone resistance among GNB colonizing community-dwelling
      people with spinal cord dysfunction is common. Colonization is more common among
      those receiving antibiotics and less common among those continent of urine. Among
      those with incontinence, those using intermittent catheterization have less
      colonization.

PMID- 17023240
TI  - Injury and demographic factors predictive of disparities in earnings after spinal
      cord injury.
AB  - OBJECTIVE: To identify differences in earnings after spinal cord injury (SCI)
      attributable to demographic factors, injury severity, and education using a
      regression model that accounts for employment status, conditional earnings
      (earnings of those employed only), and unconditional earnings (earnings from
      employment for all participants with $0 recorded for those unemployed). DESIGN:
      Secondary analysis of cross-sectional survey data. SETTING: A midwestern
      university hospital and a private hospital in the southeastern United States.
      PARTICIPANTS: Adults with traumatic SCI of at least 2 years duration and under
      the traditional retirement age of 65 completed mailed surveys (n=615).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Conditional and
      unconditional earnings. Earnings were measured by a single item that grouped
      earnings into the following 8 categories: (1) less than $10,000, (2) $10,000 to
      $14,999, (3) $15,000 to 19,999, (4) $20,000 to 24,999, (5) $25,000 to 34,999, (6)
      $35,000 to 49,999, (7) $50,000 to 74,999, and (8) $75,000 or more. RESULTS:
      Several factors investigated were significantly associated with employment status
      (sex, race, age, neurologic level of injury, ambulatory status, years since
      injury, educational level), but conditional earnings were significantly related
      to only 3 factors. Higher conditional earnings were obtained by men, non-African
      Americans, and those with a college degree. Unconditional earnings were
      significantly higher among those with the following characteristics: male, non
      African Americans, age 34 and less, ambulatory, and those who completed some
      education beyond high school. CONCLUSIONS: There are substantial differences in
      the likelihood of postinjury employment as a function of participant
      characteristics. These disparities are compounded for women, African Americans,
      and those with less than a college degree by differences in conditional earnings
      among those employed.

PMID- 17023241
TI  - Determinants of forced expiratory volume in 1 second (FEV1), forced vital
      capacity (FVC), and FEV1/FVC in chronic spinal cord injury.
AB  - OBJECTIVE: To assess factors that influence pulmonary function, because
      respiratory system dysfunction is common in chronic spinal cord injury (SCI).
      DESIGN: Cross-sectional cohort study. SETTING: Veterans Affairs Boston SCI
      service and the community. PARTICIPANTS: Between 1994 and 2003, 339 white men
      with chronic SCI completed a respiratory questionnaire and underwent spirometry.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Forced expiratory volume in
      1 second (FEV(1)), forced vital capacity (FVC), and FEV(1)/FVC. RESULTS:
      Adjusting for SCI level and completeness, FEV(1) (-21.0 mL/y; 95% confidence
      interval [CI], -26.3 to -15.7 mL/y) and FVC (-17.2 mL/y; 95% CI, -23.7 to -10.8
      mL/y) declined with age. Lifetime cigarette use was also associated with a
      decrease in FEV(1) (-3.8 mL/pack-year; 95% CI, -6.5 to -1.1 mL/pack-year), and
      persistent wheeze and elevated body mass index were associated with a lower
      FEV(1)/FVC. A greater maximal inspiratory pressure (MIP) was associated with a
      greater FEV(1) and FVC. FEV(1) significantly decreased with injury duration (-6.1
      mL/y; 95% CI, -11.7 to -0.6 mL/y), with the greatest decrement in the most
      neurologically impaired. The most neurologically impaired also had a greater
      FEV(1)/FVC, and their FEV(1) and FVC were less affected by age and smoking.
      CONCLUSIONS: Smoking, persistent wheeze, obesity, and MIP, in addition to SCI
      level and completeness, were significant determinants of pulmonary function. In
      SCI, FEV(1), FVC, and FEV(1)/FVC may be less sensitive to factors associated with
      change in airway size and not reliably detect the severity of airflow
      obstruction.

PMID- 17023242
TI  - The effect of foot and ankle prosthetic components on braking and propulsive
      impulses during transtibial amputee gait.
AB  - OBJECTIVE: To assess the influence of energy storage and return (ESAR) prosthetic
      feet and multi-axis ankles on ground reaction forces and loading asymmetry
      between lower limbs in transtibial amputees. DESIGN: Subjects wore 2 different
      prosthetic feet with and without a multi-axis ankle and were analyzed using a
      blind repeated-measures multivariate analysis-of-variance design. SETTING: Gait
      analysis laboratory. PARTICIPANTS: Fifteen healthy unilateral transtibial
      amputees (>55 y) who had an amputation at least 1 year before testing because of
      vascular disorders. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      anteroposterior ground reaction force impulse, peak ground reaction forces, and
      braking and propulsion impulse duration were analyzed as subjects walked at a
      self-selected speed while wearing each of the 4 foot-ankle prosthesis
      combinations. Statistical analyses were used to determine if there was a
      significant foot, ankle, or foot-ankle interaction effect on the outcome measures
      for each foot (P<.05). RESULTS: Amputees generated a significantly greater
      propulsive impulse with the residual leg when wearing a multi-axis ankle with the
      ESAR and non-ESAR foot, which improved the propulsive symmetry between the
      residual and intact legs. There was no prosthetic foot effect on these measures.
      There were no significant differences in the peak residual-leg braking or
      propulsive ground reaction forces or the impulse durations due to the prosthetic
      foot, ankle, or foot-ankle interactions, although an increase in the propulsive
      impulse duration approached significance (P=.062) with a multi-axis ankle.
      CONCLUSIONS: These results suggest that amputee gait may improve with the
      prescription of multi-axis ankles that allow for greater propulsive impulses by
      the residual leg, which improve the loading symmetry between legs.

PMID- 17023243
TI  - Validity of accelerometry for monitoring real-world arm activity in patients with
      subacute stroke: evidence from the extremity constraint-induced therapy
      evaluation trial.
AB  - OBJECTIVE: To examine the psychometric properties of an objective method for
      assessing real-world arm activity in a large sample with subacute stroke. DESIGN:
      Validation study. SETTING: Community. PARTICIPANTS: Persons 3 to 9 months
      poststroke (N=169) with mild to moderate motor impairment of their hemiparetic
      arm enrolled in a multisite, randomized clinical trial of constraint-induced
      movement therapy. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Participants wore an accelerometer on each arm outside the laboratory for 3 days
      before and after treatment or an equivalent no-treatment period. They also
      completed the Actual Amount of Use Test (AAUT), which is an observational measure
      of spontaneous more-impaired arm use, and the Motor Activity Log (MAL), which is
      an interview assessing more-impaired arm use in daily life. RESULTS: Low-pass
      filtered accelerometer recordings were reliable (r range, >.8) and stable (P
      range, >.48). Their validity was also supported. Correlations calculated across
      all participants at baseline between the ratio of more-impaired to less-impaired
      arm accelerometer recordings and AAUT and MAL scores were .60 and .52,
      respectively. CONCLUSIONS: Accelerometry provides an objective, real-world index
      of more-impaired arm activity with good psychometric properties.

PMID- 17023244
TI  - Botulinum toxin type A for poststroke cricopharyngeal muscle dysfunction.
AB  - OBJECTIVE: To evaluate the therapeutic effectiveness of botulinum toxin type A
      (BTX-A) in poststroke patients with cricopharyngeal muscle dysfunction. DESIGN:
      Before-after trial. SETTING: University hospital. PARTICIPANTS: Eight poststroke
      patients. INTERVENTION: BTX-A injection into the cricopharyngeal muscle under
      endoscope guidance for poststroke cricopharyngeal muscle dysfunction. MAIN
      OUTCOME MEASURES: Clinical symptom score, disability rating scale for swallowing
      impairment, videofluoroscopic swallowing study, and upper esophageal sphincter
      (UES) manometry. RESULTS: Clinical symptom score, disability rating scale for
      swallowing impairment, residue in piriform sinus, and UES pressure were all
      significantly improved at 2 weeks after BTX-A injection compared with evaluations
      before injection (P<.05). The effects on the clinical symptom score and
      disability rating scale for swallowing impairment continued to be significantly
      improved to 12 weeks after injection (P<.05). However, the residue in piriform
      sinus and the UES pressure at 12 weeks postinjection were reduced compared with
      before-injection evaluations; these results were not significant. The pharyngeal
      transit time was not changed after injection. There were no side effects observed
      in the patients studied. CONCLUSIONS: The results of the present study suggest
      that BTX-A injection may be an effective and safe treatment in patients with
      poststroke cricopharyngeal muscle dysfunction.

PMID- 17023245
TI  - Sleep-disordered breathing in fatigued postpoliomyelitis clinic patients.
AB  - OBJECTIVE: To determine the frequency, predictive factors, and symptoms
      predictive of sleep-disordered breathing (SDB) in fatigued postpoliomyelitis
      clinic patients. DESIGN: Cross-sectional, retrospective chart review. SETTING:
      University-affiliated hospital postpolio clinic. PARTICIPANTS: Postpolio clinic
      charts (N=590) were reviewed. Ninety-eight patients were included, and 492
      patients were not included, primarily because of the lack of a polysomnogram.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Apnea-Hypopnea Index
      (AHI) calculated as the total number of sleep-related breathing events/total
      sleep time. RESULTS: The frequency of SDB defined by an AHI score of 5 or more
      was 65% and by an AHI score of 10 or more was 50%. Obstructive hypopnea was the
      predominant form, occurring in 86%. Age, sex, age at acute polio, time since
      polio, weakness and respiratory difficulties at acute polio, bulbar involvement
      at acute polio and at evaluation, body mass index, pulmonary function measures,
      alcohol use, sedative drug use, smoking, fibromyalgia, kyphoscoliosis, and
      scoliosis and ear-nose-throat surgery were not predictive of SDB (AHI scores > or
      =5 and > or =10). Snoring was more common in subjects with SDB (AHI score > or =5
      and > or =10). Some pulmonary function measures correlated with oxygen saturation
      during sleep in SDB (AHI scores > or =5). CONCLUSIONS: SDB was very common in
      fatigued postpoliomyelitis clinic patients referred for sleep evaluation.
      Obstructive hypopnea was the most frequent type. In this preliminary study,
      snoring tended to predict SDB.

PMID- 17023246
TI  - Functional mobility and postural control in essential tremor.
AB  - OBJECTIVE: To evaluate functional mobility and postural control in participants
      with essential tremor (ET). DESIGN: Cross-sectional cohort study. SETTING: Motor
      performance research laboratory. PARTICIPANTS: Sixteen participants with ET
      including head tremor (age, 59.4+/-12.0 y), 14 participants with ET and no head
      tremor (age, 57.1+/-15.9 y), and 28 healthy controls (age, 58.4+/-12.4 y).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We assessed the Timed Up &
      Go, time to ascend and descend stairs, Dynamic Gait Index, and Berg Balance Scale
      (BBS). Participants completed the Activities-specific Balance Confidence Scale
      and the Human Activity Profile. We assessed postural control using center-of
      pressure measures from force platform recordings of quiet standing in 5
      conditions. RESULTS: Participants with ET including head tremor performed worse
      than controls on all functional mobility performance and self-report measures
      (P<.05) except the BBS and stair descent time. Mean performance of ET
      participants without head tremor was intermediate between the other 2 groups.
      Sway speed measures of postural control showed similar patterns, but no
      significant group differences in post hoc analysis. There were no statistically
      significant or clinically important correlations between measures of tremor
      status and functional mobility status. CONCLUSIONS: Participants with ET show
      reduced functional mobility, especially those with head tremor.

PMID- 17023247
TI  - Reliability and agreement of 5 Ergo-Kit functional capacity evaluation lifting
      tests in subjects with low back pain.
AB  - OBJECTIVE: To assess interrater reliability and agreement of 5 Ergo-Kit
      functional capacity evaluation lifting tests in subjects with low back pain
      (LBP). DESIGN: Within-subjects design, with 2 repeated measurements. SETTING:
      Academic medical center in The Netherlands. PARTICIPANTS: Twenty-four subjects
      (10 men, 14 women) with LBP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      Five Ergo-Kit lifting tests (2 isometric, 3 dynamic) were assessed on 2 occasions
      (t1, t2), by 2 different raters (R1, R2). The interval between the test sessions
      was 3 days. Interrater reliability level was expressed with the intraclass
      correlation coefficient (ICC), and the level of agreement between raters with the
      standard error (SE) of measurement. RESULTS: ICCs means (reliability) of
      isometric and dynamic Ergo-Kit lifting tests ranged from .94 to .97, and SE of
      measurement values (agreement) ranged from 1.9 to 8.6 kg. CONCLUSIONS: There was
      good reliability and agreement between raters of the isometric and dynamic Ergo
      Kit lifting tests in subjects with LBP, which supports the use of these tests to
      assess functional lifting capacity.

PMID- 17023248
TI  - Measurement of motor nerve conduction velocity of the sciatic nerve in patients
      with piriformis syndrome: a magnetic stimulation study.
AB  - OBJECTIVE: To assess the motor nerve conduction of the sciatic nerve by a
      magnetic stimulation method in patients with piriformis syndrome. DESIGN:
      Prospective study. SETTING: An electrodiagnostic laboratory in a university
      hospital. PARTICIPANTS: Twenty-three patients with piriformis syndrome and 15
      healthy persons for control. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Motor nerve conduction velocity (MNCV) of the sciatic nerve was
      measured at the gluteal segment by magnetic stimulation proximally at L5 and S1
      roots and distally at sciatic nerve at gluteal fold and recording at the
      corresponding muscles. Diagnostic sensitivities were measured in the magnetic
      stimulation method and the conventional nerve conduction, long latency reflex,
      and needle electromyography studies. RESULTS: The mean MNCV of the sciatic nerve
      +/- standard deviation at the gluteal segment in L5 component was 55.4+/-7.8 m/s
      in patients with piriformis syndrome, which was slower than the mean value of
      68.1+/-10.3 m/s obtained in healthy controls (P=.014). The MNCV of the sciatic
      nerve in S1 component showed no significant difference between the patients and
      controls (P=.062). A negative relation was found between the disease duration and
      the MNCV values of sciatic nerves in patients with piriformis syndrome (r=-.68,
      P<.01). The diagnostic sensitivity by magnetic stimulation is .467. CONCLUSIONS:
      Magnetic nerve stimulation provides a painless, noninvasive, and objective method
      for evaluation of sciatic nerve function in patients with piriformis syndrome.

PMID- 17023249
TI  - Peripheral quantitative computed tomography: measurement sensitivity in persons
      with and without spinal cord injury.
AB  - OBJECTIVES: To determine (1) the error attributable to external tibia-length
      measurements by using peripheral quantitative computed tomography (pQCT) and (2)
      the effect these errors have on scan location and tibia trabecular bone mineral
      density (BMD) after spinal cord injury (SCI). DESIGN: Blinded comparison and
      criterion standard in matched cohorts. SETTING: Primary care university hospital.
      PARTICIPANTS: Eight able-bodied subjects underwent tibia length measurement. A
      separate cohort of 7 men with SCI and 7 able-bodied age-matched male controls
      underwent pQCT analysis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      The projected worst-case tibia-length-measurement error translated into a pQCT
      slice placement error of +/-3 mm. We collected pQCT slices at the distal 4% tibia
      site, 3 mm proximal and 3 mm distal to that site, and then quantified BMD error
      attributable to slice placement. RESULTS: Absolute BMD error was greater for able
      bodied than for SCI subjects (5.87 mg/cm(3) vs 4.5 mg/cm(3)). However, the
      percentage error in BMD was larger for SCI than able-bodied subjects (4.56% vs
      2.23%). CONCLUSIONS: During cross-sectional studies of various populations, BMD
      differences up to 5% may be attributable to variation in limb-length-measurement
      error.

PMID- 17023250
TI  - Agreement between patient and proxy responses during recovery after hip fracture:
      evidence for the FIM instrument.
AB  - OBJECTIVE: To evaluate the agreement between patient and proxy responses of the
      FIM instrument at 4 different periods of time during the first 6 months after hip
      fracture. DESIGN: Prospective cohort study. SETTING: A large urban health region
      with 2 tertiary hospitals that treat hip fractures. PARTICIPANTS: Patients
      (n=137) who were 65 years or older, admitted to the health region with a primary
      diagnosis of hip fracture, who had Mini-Mental State Examination scores greater
      than 17. Family caregivers (n=137) participated as proxy respondents.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The FIM instrument.
      Agreement was evaluated at each of the 4 assessments during the 6-month follow-up
      after hip fracture using intraclass correlation coefficient. RESULTS: FIM scores
      improved over the 6 months with the greatest improvement occurring within the
      first month of recovery. Agreement was higher for more observable activities than
      less observable ones. The magnitude of agreement improved over the 6 months with
      the proportion of clinically important systematic differences decreasing over
      time. Agreement for change scores was lower than the agreement at each of the 4
      assessments. CONCLUSIONS: Patient-proxy agreement levels are acceptable; the
      agreement varies with the subscale and the recovery phase. Substitution of proxy
      for patient responses across time may be used guardedly when patient responses
      are missing.

PMID- 17023251
TI  - Interrater reliability of the history and physical examination in patients with
      mechanical neck pain.
AB  - OBJECTIVE: To examine the interrater reliability of the history and physical
      examination in patients with mechanical neck pain. DESIGN: Single-group repeated
      measures for interrater reliability. SETTING: Outpatient physical therapy clinic.
      PARTICIPANTS: Twenty-two patients with mechanical neck pain underwent a
      standardized history and physical examination by a physical therapist.
      INTERVENTION: Following a 5-minute break, a second therapist who was blind to the
      findings of examiner 1 performed the second standardized history and physical
      examination. MAIN OUTCOME MEASURES: The Cohen kappa and weighted kappa were used
      to calculate the interrater reliability of ordinal level data from the history
      and physical examination. Intraclass correlation coefficients model 2,1
      (ICC(2,1)) and the 95% confidence intervals were calculated to determine the
      interrater reliability for continuous variables. RESULTS: The kappa coefficients
      ranged from -.06 to .90 for the variables obtained from the history. Reliability
      values for categorical data collected during the physical examination ranged from
      no to substantial agreement depending on the particular test and measure.
      ICC(2,1) for cervical range of motion (ROM) measurements ranged between .66 and
      .78. CONCLUSIONS: We have reported the interrater reliability of the history and
      physical examination in a group of patients with a primary report of neck pain.
      The reliability variables varied considerably for manual assessment techniques
      and were significantly higher for the examination of muscle length and cervical
      ROM. Ultimately, it will be up to each clinician to determine if a particular
      test or measure poses adequate reliability to assist in the clinical decision
      making process.

PMID- 17023252
TI  - Reliability of electronic versus manual wound measurement techniques.
AB  - OBJECTIVE: To compare the accuracy and reliability of 3 wound measurement
      techniques, including linear and 2 electronic techniques--Visitrak and the VeV MD
      system. DESIGN: Repeated measures involving forty 2-dimensional "wounds" with a
      range of clinically relevant sizes were created using regular paper. Blinded
      observers measured the surface areas of wounds in 2 sessions, using 3 techniques.
      SETTING: Research department of a tertiary referral center. PARTICIPANTS: Four
      blinded observers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mixed
      linear models were fitted to determine interobserver and intraobserver
      variability. The average root mean square error (RMSE) for each measurement
      technique was determined to investigate the accuracy. RESULTS: Intraobserver
      variation was not significant in most measurement techniques. Interobserver
      variation was significant for all techniques. Linear measurements showed the
      highest RMSE, whereas VeV and Visitrak were comparable. CONCLUSIONS: Reliability
      of repeated wound measurements for all techniques can be achieved only with the
      same observer. Linear measurement has the least accuracy in evaluating wound
      size, VeV is slightly better than Visitrak for large wounds, and Visitrak is
      slightly better than VeV for small wounds. Our study shows that the use of
      electronic devices is superior to manual techniques to achieve valid measurements
      of wound area.

PMID- 17023253
TI  - Differences in pain perception in women using concentric and monopolar needles.
AB  - OBJECTIVE: To examine pain perception using concentric needle electrodes and
      monopolar needle electrodes in an all-female study group without underlying hand
      or arm pain complaints, using study subjects as their own controls. DESIGN:
      Prospective randomized study. Two muscles--the biceps and abductor pollicis
      brevis (APB)--were examined using both a concentric needle electrode and a
      monopolar needle electrode. SETTING: University community. PARTICIPANTS: Eighty
      healthy female employees at the University of Utah and Primary Children's
      Hospital were enrolled. All completed the study. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Pain scores. Posttest verbal analog pain scale (0-10)
      measures were obtained after each muscle was studied. A subset of subjects (n=51)
      was asked to identify needle preference after completion of the study. RESULTS:
      There was no significant difference in mean pain scores between the concentric
      needle electrode and the monopolar needle electrode (3.06 and 3.10, respectively;
      P=.803). The APB muscle was significantly more painful than the biceps muscle
      with both needle types (mean pain scores, 3.92 and 2.24, respectively; P<.001).
      In the subset of subjects asked to identify needle preference after completion of
      the study, 21 chose a concentric needle electrode and 30 a monopolar needle
      electrode. This difference was not statistically significant. However, verbal
      analog pain scores were lower with the needle preferred by each subject (P<.20).
      CONCLUSIONS: There is no significant difference in mean pain scores reported
      between a concentric needle electrode and a monopolar needle electrode. Subjects
      were clear on the needle they preferred, and the pain scores reported for the
      less painful needle were lower than those for the other needle.

PMID- 17023254
TI  - Assessment of stretching of the iliotibial tract with Ober and modified Ober
      tests: an ultrasonographic study.
AB  - OBJECTIVE: To assess stretching of the iliotibial tract with Ober and modified
      Ober tests, by assessing morphologic changes of the tract using ultrasonography
      during stretching. DESIGN: Cross-sectional study. SETTING: Orthopedic laboratory.
      PARTICIPANTS: Thirty-six healthy subjects (age, 24.3+/-4.0 y) were recruited.
      They had no history of previous low back, gluteus, hip, or knee pain and
      satisfied the inclusion criteria for this study. INTERVENTION: Each subject was
      randomly assigned to first undergo either the Ober test or the modified Ober
      test, and 30 minutes after the first to undergo the other test. Measurements were
      obtained with the subjects lying on the right side. The left knee was flexed 90
      degrees for the Ober test and positioned at 0 degrees for the modified test. MAIN
      OUTCOME MEASURES: The iliotibial tract widths in subjects were measured in 3
      gradually increased hip adduction positions (neutral, adducted, adducted with
      weight) when performing Ober and modified Ober tests. Ten of these 36 subjects
      were randomly chosen to undergo a repeat of the same protocol to test the
      reliability of ultrasonographic measurements in the iliotibial tract. RESULTS:
      Ultrasonography was reliable in measuring the width of iliotibial tract
      (intraclass correlation coefficient range, .81-.82). The width of the iliotibial
      tract was significantly reduced from the neutral to adducted position of the hip
      with both Ober (P=.001) and modified Ober (P<.001) tests. However, with further
      stretching using a greater hip adduction angle, the width of the iliotibial tract
      was only reduced with the modified Ober test. CONCLUSIONS: Both the Ober and
      modified Ober tests are effective in the initial stage of stretching of the
      iliotibial tract. However, the modified Ober test might be more effective in
      stretching the iliotibial tract if a further stretching effect is desired.

PMID- 17023255
TI  - An experimental pain model to investigate the specificity of the neurodynamic
      test for the median nerve in the differential diagnosis of hand symptoms.
AB  - OBJECTIVE: To indirectly assess the specificity of the neurodynamic test for the
      median nerve using an experimental pain model. DESIGN: Repeated-measures design.
      SETTING: Laboratory setting. PARTICIPANTS: Twenty asymptomatic participants in
      whom hand symptoms were induced by infusion of hypertonic saline into the thenar
      muscles. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain intensity of
      the induced hand symptoms and size of the painful area were evaluated in 8
      different arm positions, which correspond with different stages of the
      neurodynamic test for the median nerve. These positions have a variable degree of
      median nerve provocation at the wrist. RESULTS: Because the induced symptoms had
      a non-neural origin, changes in symptom provocation with the neurodynamic test
      would have indicated poor specificity. However, there were no statistically
      significant differences in pain perception (P> or =.22) and the recorded
      differences were negligible from a clinical perspective. CONCLUSIONS: Taking into
      consideration the limitations of an experimental pain model, this study
      indirectly confirms the specificity of the neurodynamic test for the median
      nerve. The results of this study, together with previous studies that
      demonstrated a high sensitivity, support the use of the neurodynamic test for the
      median nerve to differentially diagnose neurogenic disorders, such as carpal
      tunnel syndrome, from other wrist and hand pathologies.

PMID- 17023256
TI  - Open-label study of clarithromycin in patients with undifferentiated connective
      tissue disease.
AB  - OBJECTIVE: The macrolide family of antibiotics (erythromycin, clarithromycin, and
      others), have both antimicrobial and immunomodulatory effects. This study
      explored the effect of clarithromycin on the clinical course of patients with
      undifferentiated connective tissue disease (UCTD) in a 12-week open-label study.
      METHODS: The diagnosis of UCTD was based on symptoms/signs of connective tissue
      disease, and the presence of 1 or more positive autoimmune disease tests, but
      with insufficient criteria to make a definitive diagnosis. Screening and monthly
      follow-up visits over 12 weeks included the following: history and physical
      examination; concurrent medications; the 68/66 tender/swollen joint count; visual
      analog scores 0 to 100 mm for patient and physician global assessment of disease
      activity, and patient pain; antinuclear antibody panel, rheumatoid factor,
      erythrocyte sedimentation rate, C-reactive protein, and blood chemistry. RESULTS:
      Seven patients with rheumatic disease were treated with clarithromycin; 6 of 7
      had symptomatic relief. Two subjects treated empirically before the decision to
      perform an open-label study responded favorably. Four of 5 patients who completed
      the prospective open-label study had mean maximal improvements from baseline of
      78, 75, and 79% in patient pain, patient global, and investigator global
      assessments, respectively. Pain relief occurred as early as 1 week. Drug
      withdrawal with rechallenge in 2 patients resulted in flare followed by recapture
      of symptomatic relief. CONCLUSIONS: Clarithromycin, a macrolide antibiotic, led
      to clinical improvement in patients with UCTD. Efficacy and safety data support
      further investigation of macrolide antibiotic use as a primary or adjunctive
      treatment in various connective tissue diseases.

PMID- 17023257
TI  - Systemic rheumatoid vasculitis: a review.
AB  - OBJECTIVES: To review the most recent information on the incidence, clinical
      course, pathology, pathogenesis, diagnosis, and treatment of rheumatoid
      vasculitis (RV), including the still scanty data on the use of biologics.
      METHODS: PubMed and MEDLINE databases (1950-2006) were searched for the key words
      "vasculitis" and "rheumatoid arthritis"; and "rheumatoid arthritis" and "extra
      articular manifestations." All relevant articles in English and French were
      reviewed. Additional words used in follow-up research include "anti-TNF,"
      "rituximab," "IL-1 receptor antagonists," and "CTLA-4 Ig," all in conjunction
      with "vasculitis." Pertinent secondary references were also retrieved. RESULTS:
      RV is an inflammatory condition of the small- and medium-sized vessels that
      affects a subset of patients with established rheumatoid arthritis (RA)
      (approximately 1 to approximately 5%). It has a vast array of clinical
      manifestations with a predilection for the skin (peripheral gangrene, deep
      cutaneous ulcers) and the peripheral nervous system (mononeuritis multiplex).
      Because of the lack of specific signs and symptoms, the diagnosis relies on the
      exclusion of other causes of similar lesions (diabetes, atherosclerosis, drug
      reactions, infection, neoplasias) and, ideally, on the histopathological
      demonstration of necrotizing vasculitis. Despite the availability of a host of
      promising new drugs for the treatment of RA, no clinical trials have tested their
      efficacy in RV; therefore, its management remains largely empirical. CONCLUSIONS:
      Although RV has apparently been decreasing over the last 2 decades, possibly as a
      consequence of the more energetic approach to the management of RA currently
      used, it remains an important complication of RA that needs to be promptly
      recognized and treated.

PMID- 17023258
TI  - Power Doppler ultrasound in musculoskeletal disease: a systematic review.
AB  - OBJECTIVE: To evaluate the performance characteristics of power Doppler
      ultrasound as a diagnostic and monitoring tool in the assessment of
      musculoskeletal disease through a systematic review of the literature. METHODS: 
      SEARCH STRATEGY: We performed a literature search of PUBMED (1966 to June 2005).
      SELECTION CRITERIA: Only original research reports written in English involving
      musculoskeletal disease and power Doppler ultrasound were included. Reviews were
      noted but not included. Data Extraction/Reporting: The design, subjects, methods,
      imaging protocols, and performance characteristics studied in the research papers
      were reported. RESULTS: Of 3568 identified reports, 139 involved power Doppler
      ultrasound of the musculoskeletal system. Fifty-three of these reports met the
      inclusion criteria. Ultrasound machine settings were specified in 63% of reports.
      Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64%
      of papers). Validity was the most studied performance characteristic (94% of
      reports), while reliability and responsiveness were studied in 17 and 34%,
      respectively. CONCLUSIONS: Although the majority of research reports of power
      Doppler ultrasound assessment of the musculoskeletal system evaluated validity,
      less than half reported reliability and responsiveness. Further work is needed to
      evaluate power Doppler ultrasound assessment of the musculoskeletal system before
      it can be used to guide clinical decisions or be used as an endpoint in clinical
      trials.

PMID- 17023259
TI  - New type of kdp region with a split sensor-kinase kdpD gene located within two
      divergent kdp operons from the thermoacidophilic bacterium Alicyclobacillus
      acidocaldarius.
AB  - The kdp region from the thermoacidophilic bacterium Alicyclobacillus
      acidocaldarius consists of two divergent operons: kdpZFABCN, which is tenfold
      induced at low K+ concentrations and encodes the K+-translocating P-type ATPase
      KdpZFABC as well as KdpN, a novel covalent homo-dimer of the cytoplasmic N
      terminal part from sensor kinase KdpD; and secondly, the constitutively expressed
      kdpHE operon, encoding the remainder of KdpD and the response regulator KdpE.

PMID- 17023260
TI  - Clinical practice guidelines: a manual for developing evidence-based guidelines
      to facilitate performance measurement and quality improvement.

PMID- 17023261
TI  - The importance of discipline.

PMID- 17023262
TI  - Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis
      in ApoE knockout mice fed a Western-type diet.
AB  - Hyperlipidemia enhances xanthine oxidase (XO) activity. XO is an important source
      of reactive oxygen species (ROS). Since ROS are thought to promote
      atherosclerosis, we hypothesized that XO is involved in the development of
      atherosclerosis. ApoE(-/-) mice were fed a Western-type (WD) or control diet. In
      subgroups, tungsten (700 mg/L) was administered to inhibit XO. XO is a secreted
      enzyme which is formed in the liver as xanthine dehydrogenase (XDH) and binds to
      the vascular endothelium. High expression of XDH was found in the liver and WD
      increased liver XDH mRNA and XDH protein expression. WD induced the conversion of
      XDH to the radical-forming XO. Moreover, WD increased the hepatic expression of
      CD40, demonstrating activation of hepatic cells. Aortic tissue of ApoE(-/-) mice
      fed a WD for 6 months exhibited marked atherosclerosis, attenuated endothelium
      dependent relaxation to acetylcholine, increased vascular oxidative stress, and
      mRNA expression of the chemokine KC. Tungsten treatment had no effect on plasma
      lipids but lowered the plasma XO activity. In animals fed a control diet,
      tungsten had no effect on radical formation, endothelial function, or
      atherosclerosis development. In mice fed a WD, however tungsten attenuated the
      vascular superoxide anion formation, prevented endothelial dysfunction, and
      attenuated KC mRNA expression. Most importantly, tungsten treatment largely
      prevented the development of atherosclerosis in the aorta of ApoE(-/-) mice on
      WD. Therefore, tungsten, potentially via the inhibition of XO, prevents the
      development of endothelial dysfunction and atherosclerosis in ApoE(-/-) mice on
      WD.

PMID- 17023263
TI  - Apoptosis signal regulating kinase-1 connects reactive oxygen species to p38 MAPK
      induced mitochondrial apoptosis in UVB-irradiated human keratinocytes.
AB  - The p38 MAPK pathway controls critical premitochondrial events culminating in
      apoptosis of UVB-irradiated human keratinocytes, but the upstream mediators of
      this stress signal are not completely defined. This study shows that in human
      keratinocytes exposed to UVB the generation of reactive oxygen species (ROS) acts
      as a mediator of apoptosis signal regulating kinase-1 (Ask-1), a redox-sensitive
      mitogen-activated protein kinase kinase kinase (MAP3K) regulating p38 MAPK and
      JNK cascades. The NADPH oxidase antagonist diphenylene iodonium chloride and the
      EGFR inhibitor AG1487 prevent UVB-mediated ROS generation, the activation of the
      Ask-1-p38 MAPK stress response pathway, and apoptosis, evidencing the link
      existing between the early plasma membrane-generated ROS and the activation of a
      lethal cascade initiated by Ask-1. Consistent with this, Ask-1 overexpression
      considerably sensitizes keratinocytes to UVB-induced mitochondrial apoptosis.
      Although the JNK pathway is also stimulated after UVB, the killing effect of Ask
      1 overexpression is reverted by p38 MAPK inhibition, suggesting that Ask-1 exerts
      its lethal effects mainly through the p38 MAPK pathway. Moreover, p38alpha(-/-)
      murine embryonic fibroblasts are protected from UVB-induced apoptosis even if JNK
      activation is fully preserved. These results argue for an important role of the
      UVB-generated ROS as mediators of the Ask-1-p38 MAPK pathway that, by culminating
      in apoptosis, restrains the propagation of potentially mutagenic keratinocytes.

PMID- 17023264
TI  - Evidence that N-acetylcysteine inhibits TNF-alpha-induced cerebrovascular
      endothelin-1 upregulation via inhibition of mitogen- and stress-activated protein
      kinase.
AB  - N-acetylcysteine (NAC) is neuroprotective in animal models of acute brain injury
      such as caused by bacterial meningitis. However, the mechanism(s) by which NAC
      exerts neuroprotection is unclear. Gene expression of endothelin-1 (ET-1), which
      contributes to cerebral blood flow decline in acute brain injury, is partially
      regulated by reactive oxygen species, and thus a potential target of NAC. We
      therefore examined the effect of NAC on tumor necrosis factor (TNF)-alpha-induced
      ET-1 production in cerebrovascular endothelial cells. NAC dose dependently
      inhibited TNF-alpha-induced preproET-1 mRNA upregulation and ET-1 protein
      secretion, while upregulation of inducible nitric oxide synthase (iNOS) was
      unaffected. Intriguingly, NAC had no effect on the initial activation (i.e.,
      IkappaB degradation, nuclear p65 translocation, and Ser536 phosphorylation) of NF
      kappaB by TNF-alpha. However, transient inhibition of NF-kappaB DNA binding
      suggested that NAC may inhibit ET-1 upregulation by inhibiting (a) parallel
      pathway(s) necessary for full transcriptional activation of NF-kappaB-mediated ET
      1 gene expression. Similar to NAC, the MEK1/2 inhibitor U0126, the p38 inhibitor
      SB203580, and the protein kinase inhibitor H-89 selectively inhibited ET-1
      upregulation without affecting nuclear p65 translocation, suggesting that NAC
      inhibits ET-1 upregulation via inhibition of mitogen- and stress-activated
      protein kinase (MSK). Supporting this notion, cotreatment with NAC inhibited the
      TNF-alpha-induced rise in MSK1 and MSK2 kinase activity, while siRNA knock-down
      experiments showed that MSK2 is the predominant isoform involved in TNF-alpha
      induced ET-1 upregulation.

PMID- 17023265
TI  - Reduction in extracellular superoxide dismutase activity in African-American
      patients with hypertension.
AB  - Superoxide anions react with nitric oxide to form peroxynitrite and hence reduce
      the bioavailability of nitric oxide in the arteries. Extracellular superoxide
      dismutase (EC-SOD) is a major superoxide scavenger in human plasma and vascular
      tissues. The objective of this study is to assess whether essential hypertension
      is associated with an alteration in EC-SOD activity. In this report, blood
      samples were obtained from hypertensive (n=39) and normotensive (n=37) African
      Americans. Plasma EC-SOD activity was measured using in-gel activity staining and
      spectrophotometric assays, EC-SOD protein level was measured using Western
      blotting, nitrotyrosine was measured using slot blotting, 8-isoprostane was
      measured with an enzyme immunoassay, and plasma copper and zinc concentrations
      were measured using an atomic absorption assay. Our data demonstrate that the
      copper, zinc, and plasma EC-SOD protein concentrations in the hypertensive and
      normotensive subjects are indistinguishable. Compared to normotensive controls,
      hypertensive patients have significantly reduced plasma EC-SOD activity. Plasma
      nitrotyrosine and 8-isoprostane levels are significantly higher in the
      hypertensive patients than in normotensive controls. Results from this study
      suggest that a reduction in EC-SOD activity in hypertensive patients is not due
      to a down-regulation of the SOD3 gene (encoding EC-SOD) or deficiency in mineral
      cofactors. Furthermore, the reduced EC-SOD activity might be at least partially
      responsible for the increased oxidative stress, as reflected by increased plasma
      nitrotyrosine and 8-isoprostane, in hypertensive subjects.

PMID- 17023266
TI  - 8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via
      Rac1/STATs signaling in LPS-induced brain microglia.
AB  - Free 8-hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine
      (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is
      known about its biological function when it presents in cytosol as a free form.
      We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide
      (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity,
      and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA
      levels of pro-inflammatory cytokine, such as IL-1beta, IL-6, and TNF-alpha, in
      activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen
      species (ROS) production through reduction of NADPH oxidase activity and blocked
      Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and
      p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken
      together, these results provide new aspects of oh(8)dG as an anti-inflammatory
      agent.

PMID- 17023267
TI  - Intragastric generation of antimicrobial nitrogen oxides from saliva-
      physiological and therapeutic considerations.
AB  - Salivary nitrite is suggested to enhance the antimicrobial properties of gastric
      juice by conversion to nitric oxide (NO) and other reactive nitrogen
      intermediates in the stomach. Intubated patients exhibit extremely low gastric
      levels of NO, because they do not swallow their saliva. The present investigation
      was designed to examine the antibacterial effects of human saliva and gastric
      juice. Furthermore, we studied a new mode of NO delivery, involving formation
      from acidified nitrite, which could prevent bacterial growth in the gastric juice
      of intubated patients in intensive care units. The growth of Escherichia coli
      ATCC 25922 and the formation of NO and nitroso/nitrosyl species were determined
      after incubation of gastric juice with saliva from healthy volunteers that was
      rich (nitrate ingestion) or poor (overnight fasting) in nitrite. In a stomach
      model containing gastric juice from intubated patients, we inserted a catheter
      with a silicone retention cuff filled with ascorbic acid and nitrite and
      determined the resulting antibacterial effects on E. coli and Candida albicans.
      Saliva enhanced the bactericidal effect of gastric juice, especially saliva rich
      in nitrite. Formation of NO and nitroso/nitrosyl species by nitrite-rich saliva
      was 10-fold greater than that by saliva poor in nitrite. In our stomach model, E.
      coli and C. albicans were killed after exposure to ascorbic acid and nitrite. In
      conclusion, saliva rich in nitrite enhances the bactericidal effects of gastric
      juice, possibly through the generation of reactive nitrogen intermediates,
      including NO. Acidified nitrite inside a gas-permeable retention cuff may be
      useful for restoring gastric NO levels and host defense in critically ill
      patients.

PMID- 17023268
TI  - Induction of mitochondrial nitrative damage and cardiac dysfunction by chronic
      provision of dietary omega-6 polyunsaturated fatty acids.
AB  - Increased awareness of obesity has led to a dietary shift toward "heart-friendly"
      vegetable oils containing omega-6 polyunsaturated fatty acid (omega-6 PUFA). In
      addition to its beneficial effects, omega-6 PUFA also exhibits proinflammatory
      and prooxidative properties. We hypothesized that chronic dietary omega-6 PUFA
      can induce free radical generation, predisposing the cardiac mitochondria to
      oxidative damage. Male Wistar rats were fed a diet supplemented with 20% w/w
      sunflower oil, rich in omega-6 PUFA (HP) or normal laboratory chow (LP) for 4
      weeks. HP feeding augmented phospholipase A(2) activity and breakdown of
      cardiolipin, a mitochondrial phospholipid. HP hearts also demonstrated elevated
      inducible nitric oxide synthase expression, loss of Mn superoxide dismutase, and
      increased mitochondrial nitrotyrosine levels. In these hearts, oxidative damage
      to mitochondrial DNA (mDNA) was demonstrated by 8-hydroxyguanosine
      immunopositivity, overexpression of DNA repair enzymes, and a decrease in the
      mRNA expression of specific respiratory subunits encoded by the mDNA.
      Functionally, at higher workloads, HP hearts also demonstrated a greater decline
      in cardiac work than LP, suggesting a compromised mitochondrial reserve. Our
      study, for the first time, demonstrates that consumption of a high fat diet rich
      in omega-6 PUFA for only 4 weeks instigates mitochondrial nitrosative damage and
      causes cardiac dysfunction at high afterloads.

PMID- 17023269
TI  - Oxidation-induced changes in human lens epithelial cells. 1. Phospholipids.
AB  - Lipid compositional changes in lens epithelial cells (HLE B-3) grown in a
      hyperoxic atmosphere were studied to determine if oxidation could cause changes
      in the amount and type of phospholipid similar to those found in vivo with age
      and cataract. The phosphatidylcholines in HLE B-3 cells were 8 times more
      unsaturated than the sphingomyelins. Cell viability was the same for cells grown
      for up to 48 h in a normoxic or hyperoxic atmosphere. Lipid oxidation was about
      three times higher after growth in a hyperoxic atmosphere compared with cells
      grown in a normoxic atmosphere. The lack of change in the relative amount of
      sphingomyelin and the decrease in phosphatidylcholine coupled with the increase
      in lysophosphatidylcholine support the idea that similar mechanisms may be
      responsible for the lipid compositional changes in both lens epithelial and fiber
      cells. It is postulated that lipases eliminate oxidized unsaturated
      glycerolipids, leaving a membrane increasingly composed of more ordered and more
      saturated sphingolipids. Oxidative stress leads to changes in membrane
      composition that are consistent with those seen with age in human epithelial
      cells. Oxidation-induced epithelial phospholipid change is an area of research
      that has gone virtually unexplored in the human lens and could be relevant to all
      cell types and may be important to lens clarity.

PMID- 17023270
TI  - Viscolin, a new chalcone from Viscum coloratum, inhibits human neutrophil
      superoxide anion and elastase release via a cAMP-dependent pathway.
AB  - The mistletoe Viscum coloratum is used in traditional Chinese medicine to treat
      inflammatory diseases. In this study, a cellular model in isolated human
      neutrophils, which are important in the pathogenesis of rheumatoid arthritis,
      chronic obstructive pulmonary disease, and other inflammatory diseases, was
      established to elucidate the anti-inflammatory functions of V. coloratum. The
      partially purified extract of V. coloratum (PPE-SVC) potently inhibited formyl-L
      methionyl-L-leucyl-L-phenylalanine (FMLP)-induced superoxide anion generation and
      elastase release in a concentration-dependent manner with IC(50) values of 0.58+/
      0.03 and 4.93+/-0.54 microg/ml, respectively. Furthermore, a new chalcone
      derivative, viscolin (4',4''-dihydroxy-2',3',6',3''-tetramethoxy-1,3
      diphenylpropane), was isolated from PPE-SVC. Viscolin was demonstrated to inhibit
      superoxide anion generation and elastase release, as well as to accelerate
      resequestration of cytosolic calcium in FMLP-activated human neutrophils.
      Furthermore, the inhibitory effects of viscolin were reversed by protein kinase A
      (PKA) inhibitor, suggesting that PKA mediates the viscolin-caused inhibitions.
      Viscolin induced a substantial increase in cAMP levels, and that occurred through
      the inhibition of phosphodiesterase (PDE) activity but not an increase in
      adenylate cyclase function. Consistent with this, viscolin potentiated the PGE(1)
      caused inhibition of superoxide anion release and calcium mobilization, as well
      as elevation of cAMP formation. These results demonstrate that inhibition of
      inflammatory responses in human neutrophils by viscolin is associated with an
      elevation of cellular cAMP through inhibition of PDE. Comparable results were
      also observed by PPE-SVC, indicating that the effect of PPE-SVC is at least
      partly mediated by viscolin. In summary, viscolin is a novel inhibitor of PDE and
      might be useful for treatment of neutrophilic inflammation.

PMID- 17023271
TI  - Reversible inhibition of mitochondrial complex I activity following chronic
      dopaminergic glutathione depletion in vitro: implications for Parkinson's
      disease.
AB  - The pathogenesis underlying the selective degeneration of nigral dopaminergic
      neurons in Parkinson's disease is not fully understood but several lines of
      evidence implicate the role of oxidative stress and mitochondrial dysfunction.
      Depletion in levels of the thiol reducing agent glutathione (GSH + GSSG) is the
      earliest reported biochemical event to occur in the Parkinsonian substantia nigra
      prior to selective loss of complex I (CI) activity associated with the disease
      believed to contribute to subsequent dopaminergic cell death. Recent studies from
      our laboratory have demonstrated that acute reduction in both cellular and
      mitochondrial glutathione levels results in increased oxidative stress and a
      decrease in mitochondrial function linked to a selective decrease in CI activity
      through an NO-mediated mechanism (Jha, N.; Jurma, O.; Lalli, G.; Liu, Y.; Pettus,
      E. H.; Greenamyre, J. T.; Liu, R. M.; Forman, H. J.; Andersen, J. K. Glutathione
      depletion in PC12 results in selective inhibition of mitochondrial complex I
      activity. Implications for Parkinson's disease J. Biol. Chem. 275: 26096-26101;
      2000. Hsu, M.; Srinivas, B.; Kumar, J.; Subramanian, R.; Andersen, J. Glutathione
      depletion resulting in selective mitochondrial complex I inhibition in
      dopaminergic cells is via an NO-mediated pathway not involving peroxynitrite:
      implications for Parkinson's disease J. Neurochem. 92: 1091-1103.2005.). However,
      the effect of prolonged glutathione depletion on dopaminergic cells is not known.
      In this present study, using low concentrations of buthionine-S-sulfoximine, a
      chemical inhibitor of the de novo glutathione synthesizing enzyme glutamate
      cysteine ligase, we developed a chronic model in which glutathione depletion in
      dopaminergic N27 cells for a 7-day period was found to lead to inhibition of CI
      activity via a peroxynitrite-mediated event which is reversible by the thiol
      reducing agent, dithiothreitol, and coincides with increased S-nitrosation of
      mitochondrial proteins.

PMID- 17023272
TI  - PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal.
AB  - Although surgical removal is a primary option for treating tumors, it can lead to
      the increased growth of metastatic tumors. Because surgical procedures may
      generate reactive oxygen species (ROS), known promoters of tumor metastasis and
      growth, we investigated whether PEGylated catalase (PEG-catalase, plasma half
      life of 13.6 h) was able to prevent this after surgical removal of a footpad
      tumor in mice. Murine melanoma cells labeled with the firefly luciferase gene
      were used to monitor the distribution of tumor cells. After inoculation into the
      footpad, tumor cells were found in the lung, and the number increased with time.
      The surgical removal of the footpad tumor significantly (p < 0.05) increased the
      number of metastatic tumor cells and the level of plasma lipoperoxides. An
      intravenous injection of PEG-catalase significantly (p < 0.05) suppressed the
      metastatic tumor growth as well as the peroxidation. Quantitative RT-PCR and
      Western blot analyses indicated that PEG-catalase markedly reduced the increase
      in the expression of epidermal growth factor receptor. These findings indicate
      that the removal of tumor produces ROS, which then aggravate metastatic tumor
      growth by activating several growth factors. PEG-catalase can effectively prevent
      this metastatic tumor growth by detoxifying the ROS.

PMID- 17023273
TI  - Antioxidant function of corneal ALDH3A1 in cultured stromal fibroblasts.
AB  - Aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in epithelial cells and
      stromal keratocytes of mammalian cornea and is believed to play an important role
      in cellular defense. To explore a potential protective role against oxidative
      damage, a rabbit corneal fibroblastic cell line (TRK43) was stably transfected
      with the human ALDH3A1 and subjected to oxidative stress induced by H(2)O(2),
      mitomycin C (MMC), or etoposide (VP-16). ALDH3A1-transfected cells were more
      resistant to H(2)O(2,) MMC, and VP-16 compared to the vector-transfected cells.
      All treatments induced apoptosis only in vector-transfected cells, which was
      associated with increased levels of 4-hydroxy-2-nonenal (4-HNE)-adducted
      proteins. Treatment with H(2)O(2) resulted in a rise in reduced glutathione (GSH)
      levels in all groups but was more pronounced in the ALDH3A1-expressing cells.
      Treatment with the DNA-damaging agents led to GSH depletion in control groups,
      although the depletion was significantly less in ALDH3A1-expressing cells.
      Increased carbonylation of ALDH3A1 but not significant decline in enzymatic
      activity was observed after all treatments. In conclusion, our results suggest
      that ALDH3A1 may act to protect corneal cells against cellular oxidative damage
      by metabolizing toxic lipid peroxidation products (e.g., 4-HNE), maintaining
      cellular GSH levels and redox balance, and operating as an antioxidant.

PMID- 17023274
TI  - Redox proteomic identification of oxidized cardiac proteins in adriamycin-treated
      mice.
AB  - Adriamycin (ADR) is a potent anticancer drug, but its use is limited by a dose
      dependent cardiotoxicity. Oxidative stress is regarded as the mediating mechanism
      of ADR cardiotoxicity. However, cardiac proteins that are oxidatively modified
      have not been well characterized. We took a redox proteomics approach to identify
      increasingly oxidized murine cardiac proteins after a single injection of ADR
      (ip, 20 mg/kg body wt). The specific carbonyl levels of three proteins were
      significantly increased, and these proteins were identified as triose phosphate
      isomerase (TPI), beta-enolase, and electron transfer flavoprotein-ubiquinone
      oxidoreductase (ETF-QO). TPI and enolase are key enzymes in the glycolytic
      pathway, and ETF-QO serves as the transporter for electrons derived from a
      variety of oxidative processes to the mitochondria respiratory chain. Cardiac
      enolase activity in ADR-treated mice was reduced by 25%, whereas the cardiac TPI
      activity remained unchanged. Oxidation of purified enolase or TPI via Fenton
      chemistry led to a 17 or 23% loss of activity, respectively, confirming that a
      loss of activity was the consequence of oxidation. The observation that these
      cardiac enzymes involved in energy production are more oxidized resulting from
      ADR treatment indicates that the bioenergetic pathway is an important target in
      ADR-initiated oxidative stress.

PMID- 17023275
TI  - Extracellular generation of hydrogen peroxide is responsible for activation of
      EGF receptor by ultraviolet A radiation.
AB  - Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR)
      have been proposed to be activated in cells exposed to ultraviolet A (UVA)
      radiation (320-400 nm) and to be involved in photocarcinogenesis. Singlet oxygen
      and hydrogen peroxide are being discussed as mediators of the activation of
      signal transduction pathways by UVA. It is demonstrated here that EGFR is not
      activated in cells exposed to UVA in the absence of extracellular
      photosensitizers. Rather, UVA was capable of activating the EGFR and the related
      ErbB2 receptor tyrosine kinase in HeLa cells and human keratinocytes only under
      conditions that allowed for the extracellular photochemical generation of
      H(2)O(2), such as when cells were covered with cell culture medium during
      exposure to UVA. Pretreatment of cells with vanadate was required for UVA-induced
      EGFR activation, pointing to the involvement of protein tyrosine phosphatases.
      Unlike H(2)O(2), photochemically generated singlet oxygen did not activate EGFR
      but instead impaired the activation of EGFR by its ligand, EGF. In summary,
      extracellularly generated H(2)O(2) mediates UVA-induced activation of the EGFR
      and of ErbB2, whereas intracellular generation of reactive oxygen species upon
      exposure of cells to UVA is not sufficient for activation of the receptor.

PMID- 17023276
TI  - Redox modulation of the hepatitis C virus replication complex is calcium
      dependent.
AB  - Reactive species and perturbation of the redox balance have been implicated in
      the pathogenesis of many viral diseases, including hepatitis C. Previously, we
      made a surprising discovery that concentrations of H(2)O(2) that are nontoxic to
      host cells disrupted the hepatitis C virus (HCV) replication complex (RC) in Huh7
      human hepatoma cells in a manner that suggested signaling. Here, we show that
      H(2)O(2) and interferon-gamma have comparable effects on the HCV subgenomic and
      genomic RNA replication in Huh7 cells. H(2)O(2) induced a gradual rise in the
      intracellular calcium concentration ([Ca(2+)](i)). Both rapid and sustained
      suppression of HCV RNA replication by H(2)O(2) depended on this calcium
      elevation. The peroxide-induced [Ca(2+)](i) elevation was independent of
      extracellular calcium and derived, at least in part, from the endoplasmic
      reticulum. Likewise, the suppression of the HCV RC by H(2)O(2) was independent of
      extracellular calcium but required an intracellular calcium source. Other agents
      that elevated [Ca(2+)](i) could also suppress the HCV RC, suggesting that calcium
      elevation might be sufficient to suppress HCV RNA replication. In conclusion,
      oxidants may modulate the HCV RC through calcium. Effects on the infectivity and
      the morphogenesis of HCV remain to be determined. These findings suggest possible
      regulatory roles for redox and calcium signaling during viral infections.

PMID- 17023277
TI  - Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer.
AB  - Tobacco smoking is a major risk factor for lung cancer causing, among other
      effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA
      adducts can be induced by direct DNA oxidation and by lipid peroxidation. We
      measured the relationship between bronchial MDA-DNA adducts and tobacco smoking,
      cancer status, and selected polymorphisms in 43 subjects undergoing a
      bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in
      current smokers than in never smokers (frequency ratio (FR) = 1.51, 95%
      confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung
      cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI
      1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher
      levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04
      2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts
      over the median showed a worse, but not statistically significant, survival,
      after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65
      9.44). Our findings reinforce the role of smoking in lung carcinogenesis through
      oxidative stress. Subjects who carry at least one variant allele of the CCND1
      gene could accumulate DNA damage for altered cell-cycle control and reduced DNA
      repair proficiency.

PMID- 17023278
TI  - Underutilization of paravertebral block in thoracic surgery.

PMID- 17023279
TI  - Preoperative multiple-injection thoracic paravertebral blocks reduce
      postoperative pain and analgesic requirements after video-assisted thoracic
      surgery.
AB  - OBJECTIVE: The hypothesis was tested that preoperative multiple-injection
      thoracic paravertebral blocks reduce opioid requirements and promote early
      ambulation after video-assisted thoracic surgery procedures. DESIGN: Prospective,
      randomized, controlled, blinded study. SETTING: Single-university hospital.
      PARTICIPANTS: Fifty consenting patients undergoing video-assisted thoracic
      surgery. INTERVENTIONS: Patients were randomly assigned to receive preoperative
      multiple-injection thoracic paravertebral blocks (PVB group, n = 25) or
      preoperative multiple subcutaneous saline injections at the same site as in the
      PVB group (control group, n = 25). MEASUREMENTS AND MAIN RESULTS: Intraoperative
      fentanyl consumption was lower in the PVB group (p < 0.01). The time to first
      analgesic requirement was longer, and pain score at this time was lower in the
      PVB group (p < 0.05 and p < 0.01, respectively). Postoperative pain scores both
      at rest and coughing were lower during the first 4 hours in the PVB group than
      those in the control group (p < 0.01 for 0 hours and p < 0.05 for 1, 2, and 4
      hours). Cumulative morphine consumption was significantly less in the PVB group
      at all time points (p < 0.05 for 12 hours and p < 0.01 for all other time
      points), but there were no significant differences in sedation scores between the
      2 groups. There were no complications because of the blocks. Patient satisfaction
      with the analgesia was significantly greater (p < 0.05), and first mobilization
      and hospital discharge were quicker (p < 0.01 and p < 0.05, respectively) in the
      PVB group. CONCLUSION: Perioperative multiple-injection thoracic paravertebral
      blocks with bupivacaine containing epinephrine provided effective pain relief and
      a significant reduction in opioid requirements. This approach may also contribute
      to earlier postoperative ambulation after video-assisted thoracic surgery.

PMID- 17023280
TI  - Paravertebral ropivacaine, 0.3%, and bupivacaine, 0.25%, provide similar pain
      relief after thoracotomy.
AB  - OBJECTIVE: This study was designed to determine whether ropivacaine plus fentanyl
      was as effective as bupivacaine plus fentanyl in a continuous thoracic
      paravertebral block after posterolateral thoracotomy. DESIGN: Patients were
      randomly assigned in a blinded fashion to receive 1 of 2 solutions for
      paravertebral analgesia. SETTING: Multi-institutional university hospital.
      PARTICIPANTS: Sixty patients undergoing elective thoracotomy. INTERVENTIONS: A
      continuous paravertebral infusion of 0.1 mL/kg/h of either 0.3%
      ropivacaine/fentanyl, 3 microg/mL, or 0.25% bupivacaine/fentanyl, 3 microg/mL,
      was started on admission to the intensive care unit. MEASUREMENTS AND MAIN
      RESULTS: Pain scores (rest, deep breathing, and coughing), spirometry,
      subcutaneous opioids, or nonsteroidal anti-inflammatory drug consumption and
      adverse events were assessed for 48 hours. Both techniques provided adequate pain
      relief for the first 2 days after posterolateral thoracotomy. There were no
      differences between groups in pain scores at rest, coughing, or movement. There
      was an improvement of spirometry values between the first and second day in both
      groups. There were no differences in the requirements for rescue analgesia and
      side effects between groups. CONCLUSIONS: It is concluded that both bupivacaine,
      0.25%, and ropivacaine, 0.3%, with fentanyl are equally effective for post
      thoracotomy pain control when used via continuous paravertebral blockade.

PMID- 17023281
TI  - Hemodynamic effects of lidocaine in the thoracic paravertebral space during one
      lung ventilation for thoracic surgery.
AB  - OBJECTIVE: There is increasing interest in the use of the thoracic paravertebral
      block (TPVB) in association with general anesthesia for lung-resection surgery.
      The aim of the study was to evaluate the hemodynamic effects of a 5-mg/kg
      lidocaine bolus injected in the thoracic paravertebral space during one-lung
      ventilation (OLV) in noncardiac patients undergoing thoracic surgery. DESIGN:
      Prospective, observational study. SETTING: Tertiary care university hospital.
      PARTICIPANT: Twenty patients undergoing thoracotomy for lung resection.
      INTERVENTIONS: In addition to standard monitoring, cardiac output, preload
      parameters (global diastolic volume, total intrathoracic blood volume, and
      systolic volume variation), and myocardial contractility (dP(max) and cardiac
      function index) were measured with an aortic transpulmonary thermodilution
      technique. MEASUREMENTS AND MAIN RESULTS: After OLV initiation, a paravertebral
      lidocaine bolus of 5 mg/kg (2%) caused decreases in the dP(max) and cardiac
      function index that lasted up to 30 minutes. Accompanying minor reductions in
      heart rate and systolic blood pressure required no vasoactive drugs and were self
      limiting. None of the other hemodynamic parameters studied was significantly
      altered. CONCLUSIONS: In noncardiac patients, TPVB is associated with good
      hemodynamic stability, despite a small and transient decrease in myocardial
      contractility that could be related to the drug's systemic effects after its
      absorption.

PMID- 17023282
TI  - Teaching practices of thoracic epidural anesthesia in the United States: should
      lumbar epidurals be taught before thoracic epidurals?
AB  - OBJECTIVE: The purpose of this study was to determine the current teaching
      practice of thoracic epidural procedures in the United States and to determine
      the effect of the teaching sequence of thoracic and lumbar epidurals on technical
      difficulties and complications. DESIGN AND SETTING: The first part was a survey,
      which was distributed to all American Board of Anesthesiology-accredited
      programs. The second part was a noninterventional retrospective review of 2,007
      epidural procedures in a university teaching program. INTERVENTIONS: The survey
      questions were designed to determine the number of epidural procedures performed
      monthly on various services, teaching sequence, insertion technique, indications,
      and service provider. RESULTS: The survey received 81 responses (60%) from 134
      programs; 34% of the programs placed more thoracic than lumbar epidurals, 92% of
      the programs placed epidurals mainly for postoperative pain control, and 88% of
      programs mainly teach lumbar before thoracic epidurals, whereas only 10 programs
      (12%) mainly teach residents thoracic before lumbar epidurals. The authors'
      residents were divided into 2 groups: group 1 (42 residents, 70%) who learned
      thoracic before lumbar epidurals and group 2 (18 residents, 30%) who learned
      lumbar before thoracic epidurals during their earlier obstetric anesthesia
      training. There were no significant differences between the 2 groups in the
      degree of technical difficulties or the incidence of procedure-related
      complications. CONCLUSIONS: Thoracic epidurals are widely taught in the United
      States. Most programs teach lumbar before thoracic epidurals. Thoracic epidurals
      are safe to teach without prior experience with lumbar epidurals.

PMID- 17023283
TI  - Which is a better position for insertion of a high thoracic epidural catheter:
      sitting or lateral decubitus?
AB  - OBJECTIVE: The purpose of this study was to compare the safety and success rates
      associated with the placement of a high thoracic epidural catheter in the sitting
      vs. the lateral decubitus position. DESIGN: Prospective randomized study.
      SETTING: University hospital. PARTICIPANTS: Forty-one patients scheduled for off
      pump coronary artery bypass graft surgery (OPCAB) by means of high thoracic
      epidural anesthesia at Th 1/2. INTERVENTIONS: The epidural catheter was placed
      into the patients in the sitting or lateral decubitus position. The success
      rates, the time for catheter insertion, the incidence of adverse events, and the
      accuracy of the catheterization in both groups were compared. MEASUREMENTS AND
      MAIN RESULTS: The success rates in both groups were comparable, whereas 20% of
      patients showed a vagal reflex during epidural catheterization in the sitting
      group (p < 0.05). The insertion time in the sitting group was significantly
      shorter than in the lateral decubitus group (p < 0.05). Accuracy at the first
      attempt to the Th1/2 epidural space was 93% in the sitting group and 73% in the
      lateral decubitus group, but there was no statistically significant difference (p
      = 0.186). CONCLUSIONS: It is recommended to use the lateral decubitus position
      for high thoracic epidural catheterization in patients scheduled for OPCAB to
      avoid vagal reflexes.

PMID- 17023284
TI  - A pulsatile pressure waveform is a sensitive marker for confirming the location
      of the thoracic epidural space.
AB  - OBJECTIVES: The purpose of this study was to assess the validity of using a
      pulsatile, pressure waveform transduced from the epidural space through an
      epidural needle or catheter to confirm correct placement for maximal analgesia
      and to compare 3 different types of catheters' ability to transduce a waveform.
      DESIGN: A single-center, prospective, randomized trial. SETTING: A tertiary
      referral hospital. PARTICIPANTS: Eighty-one patients undergoing posterolateral
      thoracotomy who required a thoracic epidural catheter for postoperative pain
      management. INTERVENTIONS: Each epidural needle and each epidural catheter was
      transduced to determine if there was a pulsatile waveform exhibited. MEASUREMENTS
      AND MAIN RESULTS: Sensitivity of the pulsatile waveform transduced through an
      epidural needle to identify correct placement of the epidural needle and the
      sensitivity of each catheter type to identify placement were compared. In 79 of
      81 cases (97.5%), the waveform transduced directly through the epidural needle
      had a pulsatile characteristic as determined by blinded observers. In a total of
      53 of 81 epidural catheters (65.4%), the transduced waveform displayed
      pulsations. Twenty-four of 27 catheters in group S-P/Sims Portex (Smiths Medical
      MD, Inc, St Paul, MN) (88.9%) transduced a pulsatile tracing from the epidural
      space, a significantly greater percentage than in the other 2 groups (p = 0.02).
      CONCLUSIONS: The technique of transducing the pressure waveform from the epidural
      needle inserted in the epidural space is a sensitive and reliable alternative to
      other techniques for confirmation of correct epidural catheter placement. The
      technique is simple, sensitive, and inexpensive and uses equipment available in
      any operating room.

PMID- 17023285
TI  - Assessment of thoracic epidural analgesia during general anesthesia using
      pupillary reflex dilation: a preliminary study.
AB  - OBJECTIVE: Pupillary reflex dilation (PRD) secondary to noxious stimulation
      accurately predicts sensory block during combined lumbar epidural/general
      anesthesia. Therefore, the adequacy of PRD-guided thoracic epidural infusion
      during general anesthesia for thoracotomy was studied. DESIGN: Prospective study.
      SETTING: University hospital. PARTICIPANTS: Thirteen patients undergoing
      thoracotomy. INTERVENTIONS: An epidural catheter was placed at the T3-T4 level
      with initial infusion rate of 5 mL/h of ropivacaine 0.5%. Propofol/remifentanil
      target-controlled infusion was used for induction and maintenance of general
      anesthesia. Remifentanil effect site concentration was maintained constant at 0.5
      ng/mL during surgery. By using a portable pupillometer, PRD secondary to tetanic
      stimulation of the C8, T2, and T4 segments were evaluated. Ropivacaine flow rate
      was adapted half hourly, according to PRD testing and a predefined algorithm. At
      the end of surgery, PRD was tested in the 3 investigated segments, and general
      anesthesia was stopped. After emergence, these zones were tested for their
      sensitivity to cold. Pain was evaluated by using the visual analog scale.
      RESULTS: Pain scores were <3 of 10 in 84.6% of the patients. Mean PRD was 0.9 +/-
      0.6 mm in unblocked levels versus 0.2 +/- 0.5 mm in blocked segments (p = 0.02).
      PRD >or= 0.5 mm was predictive of incomplete block (sensitivity 76%, specificity
      79%, and positive predictive value 86%). PRD >or= 1 mm was highly predictive of
      inadequate block (sensitivity 73%, specificity 91%, and positive predictive value
      94%). CONCLUSION: PRD-guided continuous thoracic epidural analgesia under low
      dose remifentanil/propofol anesthesia is feasible and ensures good postoperative
      analgesia.

PMID- 17023286
TI  - Use of cardiopulmonary bypass for lung transplantation: a 10-year experience.
AB  - OBJECTIVE: The use of cardiopulmonary bypass (CPB) for lung transplantation (LTx)
      has been reported previously. This study reports the authors' experience of
      planned and unplanned use of cardiopulmonary bypass for LTx. DESIGN: Case series.
      SETTING: A university teaching hospital. PARTICIPANTS: Patients undergoing LTx.
      INTERVENTIONS: A retrospective analysis of the charts of all patients having
      undergone LTx over the last 10 years. MEASUREMENTS AND MAIN RESULTS: Among 140
      LTx, 23 (16%) were performed with the use of CPB. CPB was planned in 11 cases and
      unplanned in the 12 other cases. The use of CPB is associated with a longer
      period of postoperative mechanical ventilation, more pulmonary edema, more blood
      transfusion requirement, and an increase in postoperative mortality at 48 hours
      and 1 month. Surgical difficulties related to the dissection of the native left
      lung and acute right ventricular failure are the main reasons for unscheduled use
      of CPB. CONCLUSION: Scheduled and unscheduled CPB for LTx are associated with an
      increased mortality at 1 month and 1 year.

PMID- 17023287
TI  - Renal dysfunction after thoracic aortic surgery requiring deep hypothermic
      circulatory arrest: definition, incidence, and clinical predictors.
AB  - OBJECTIVE: The purpose of this study was to evaluate renal dysfunction (RD) after
      thoracic aortic surgery (TAS) requiring deep hypothermic circulatory arrest
      (DHCA), to determine the influence of definition on RD after TAS-DHCA, to
      determine univariate predictors of RD after TAS-DHCA, and to determine
      multivariate predictors for RD TAS-DHCA. RD was defined in 3 ways: (1) >25%
      reduction in creatinine clearance, (2) >50% increase in serum creatinine, and (3)
      >50% increase in serum creatinine with an abnormal peak serum creatinine (>1.3
      mg/dL for men and >1.0 mg/dL for women). STUDY DESIGN: Retrospective and
      observational. STUDY SETTING: Single large university hospital. PARTICIPANTS: All
      adults requiring TAS-DHCA in 2000 and 2001. MAIN RESULTS: The cohort size was
      144. Antifibrinolytic exposure was 100%: aprotinin 66% and aminocaproic acid 34%.
      The incidence of RD TAS-DHCA was 22.9% to 38.2%, depending on the definition. The
      incidence of renal replacement therapy was 2.8%. Multivariate predictors for RD
      after TAS-DHCA were sepsis, aprotinin exposure, preoperative hypertension, age,
      and donor exposures. CONCLUSIONS: Although RD after TAS-DHCA varies substantially
      because of definition, it is still very common. Its multivariate predictors merit
      further focused research to enhance perioperative protection of the kidney.

PMID- 17023288
TI  - Deep hypothermia and the vascular response to thiopental.
AB  - OBJECTIVE: The vascular response to intravenous thiopental in patients on
      cardiopulmonary bypass during deep hypothermia was examined. DESIGN: This was a
      prospective observational study. SETTING: A university teaching hospital.
      PARTICIPANTS: Twenty-one consecutive adult patients undergoing pulmonary
      thromboendarterectomy during which deep hypothermic circulatory arrest was
      instituted. INTERVENTIONS: Immediately before circulatory arrest, each patient
      was administered a 500-mg dose of thiopental intravenously. Arterial blood
      pressure was monitored and recorded by using a femoral artery catheter and serum
      electrolytes, acid-base status and arterial hematocrit were determined
      immediately before the administration of thiopental. MEASUREMENTS AND MAIN
      RESULTS: Thiopental was associated with a dose-related increase in mean arterial
      pressure of 32 +/- 11 mmHg (p < 0.0001). Thiopental also resulted in an increase
      in arterial pH of 0.08 +/- 0.03. A positive correlation between the magnitude of
      the pH change and the magnitude of the hypertensive response was suggested but
      did not reach statistical significance (p = 0.066). Of the other factors
      investigated, only serum-ionized calcium had a statistically significant
      association with the vascular response in that higher ionized calcium was
      associated with less hypertensive response (p = 0.014). CONCLUSIONS: The
      administration of thiopental to deeply hypothermic patients during
      cardiopulmonary bypass is associated with a dramatic increase in mean arterial
      blood pressure. The mechanism responsible for this vasoconstrictive response may
      involve thiopental's potentiation of the effects of norepinephrine in the
      peripheral vasculature.

PMID- 17023289
TI  - Effects of sevoflurane on biomechanical markers of hepatic and renal dysfunction
      after coronary artery surgery.
AB  - OBJECTIVE: The purpose of this study was to compare the effects of a total
      intravenous and a volatile anesthetic regimen on biochemical markers of hepatic
      and renal dysfunction after coronary artery surgery. DESIGN: Prospective, double
      blind, randomized clinical study. SETTING: University hospital, single
      institutional. PARTICIPANTS: Three hundred twenty patients undergoing elective
      coronary artery surgery were divided into 2 different anesthetic protocols:
      propofol group (n = 160) and sevoflurane group (n = 160). INTERVENTIONS:
      Hemodynamic data were registered before the start of surgery, before the start of
      CPB, 15 minutes after the end of CPB, at arrival in the intensive care unit, and
      6 and 12 hours after arrival in the intensive care unit. Serum glutamic
      oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT),
      serum lactate dehydrogenase (LDH), and serum creatinine concentrations were
      measured before surgery, at arrival in the intensive care unit, and after 6, 12,
      24, and 48 hours. MEASUREMENTS AND MAIN RESULTS: Postoperative levels of serum
      SGOT, SGPT, and LDH increased transiently in both anesthetic groups, but the
      increase was significantly lower in the sevoflurane group compared with the
      propofol group. Creatinine levels remained largely unchanged in both groups.
      CONCLUSION: Postoperative biochemical markers of hepatic dysfunction were lower
      with a sevoflurane-based anesthetic regimen in patients undergoing coronary
      artery surgery with cardiopulmonary bypass.

PMID- 17023291
TI  - Paraplegia after thoracotomy: an unusual cause.

PMID- 17023290
TI  - The effects of meperidine in the pulmonary vascular bed of the cat.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that meperidine
      induces a dilator response in the feline pulmonary vascular bed, and to identify
      receptors involved in the mediation or modulation of these effects. DESIGN:
      Prospective vehicle controlled study. SETTING: University research laboratory.
      SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In
      separate experiments, the effects of diphenydramine (histamine H(1)-receptor
      antagonist), glibenclamide (adenosine triphosphate-sensitive K+ channel blocker),
      L-N(5)-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase
      inhibitor), naloxone (opioid receptor antagonist), and nimesulide (selective
      cyclooxygenase-2 inhibitor) were investigated on pulmonary arterial responses to
      meperidine and other agonists in the feline lung bed. MEASUREMENTS AND MAIN
      RESULTS: The systemic pressure and lobar arterial perfusion pressure were
      continuously monitored, electronically averaged, and permanently recorded. Under
      elevated tone conditions in the isolated left lower lobe vascular bed of the cat,
      meperidine induced a dose-dependent vasodilator response that was not
      significantly altered after administration of glibenclamide, L-NIO, and
      nimesulide. Responses to meperidine were significantly attenuated after the
      administration of diphenydramine and naloxone. CONCLUSIONS: The results suggest
      that meperidine has potent vasodilator activity in the feline pulmonary vascular
      bed, and these responses are mediated or modulated, in part, by opioid and
      histamine receptor-sensitive pathways.

PMID- 17023292
TI  - Suitability of the lumbar test dose for the thoracic epidural space.

PMID- 17023293
TI  - The use of thoracic epidural analgesia in a patient with multiple sclerosis and
      severe kyphoscoliosis.

PMID- 17023294
TI  - Scheduled cardiothoracic surgery and Parkinson's disease: how to deal with deep
      brain stimulation.

PMID- 17023295
TI  - Coronary artery bypass grafting after left pneumonectomy.

PMID- 17023296
TI  - Inhaled iloprost in lung transplantation: can it avoid extracorporeal circulation
      in patients with severe pulmonary hypertension?

PMID- 17023298
TI  - Treatment of pulmonary arterial hypertension with sildenafil: from
      pathophysiology to clinical evidence.

PMID- 17023297
TI  - Use of nitric oxide for treatment of pulmonary hypertensive crisis in a child
      after protamine administration.

PMID- 17023299
TI  - Case 5-2006: recombinant factor VIIa in the management of postoperative bleeding
      after repair for inadvertently thrombolysed acute type A aortic dissection.

PMID- 17023300
TI  - Pro: Veno-veno bypass should routinely be used during liver transplantation.

PMID- 17023301
TI  - Con: venovenous bypass should not be used in orthotopic liver transplantation.

PMID- 17023302
TI  - Do you know a pneumo?

PMID- 17023303
TI  - An unusual transesophageal echocardiographic finding after Gore-Tex patch closure
      of an atrial septal defect.

PMID- 17023304
TI  - Comparison of lumbar epidural tramadol and lumbar epidural morphine for pain
      relief after thoracotomy: a repeated-dose study.

PMID- 17023306
TI  - Endoscopic saphenous vein harvest: severe hypercarbia.

PMID- 17023307
TI  - Multimodal analgesia for chest tube removal after cardiac surgery.

PMID- 17023308
TI  - Recombinant factor VIIa in intractable bleeding due to severe mediastinitis.

PMID- 17023309
TI  - Management of major hemorrhage during mediastinoscopy.

PMID- 17023311
TI  - 11th International Biophysics Conference. Budapest, Hungary, 25-30 July 1993.
      Preface.

PMID- 17023312
TI  - On the origin of biological information.

PMID- 17023313
TI  - Conditions for periodic and aperiodic behavior of formal neural nets.
AB  - Formal neural networks (FNN) can display dynamical behaviours, more or less
      different from each other depending on their units, the functions attributed to
      these units, interconnections, parameters, state spaces and initial states, etc.
      Whatever is 'chaos' - of which several practical and more exact definitions exist
      -, it used to be emerging at special conditions. Its prediction most often
      requires an individual analysis of the dynamical system (DS) in question. A study
      of such conditions is usually necessary in order to reach suitable control, which
      now seems to become a new trend in chaos theory. In chaos control tasks quick
      commands and at least short-term foresight of trends are required. It is a
      primary question also to define in advance what is regarded to be a controlled
      case of chaos. Possible importance of these general considerations at molecular
      scale is also discussed, avoiding not well-founded speculations.

PMID- 17023315
TI  - Effect of modification of the chromophore in retinochrome.
AB  - 14-Methyl-, 14-chloro-, 14-fluoro-retinals have been incorporated into apo
      retinochrome to investigate the effect of the electronegativities of C-14
      substituents on the protonation of the Schiff base. The extent of protonation
      decreased in going from 14-methyl- to 14-chloro- to 14-fluoro-retinal. There was
      usually no protonation in the case of the 14-fluoro analogue. The chromophore
      protein interactions are also discussed.

PMID- 17023316
TI  - Bacteriorhodopsin: the effect of bilayer thickness on 2D-array formation, and the
      structural re-alignment of retinal through the photocycle.
AB  - From our earlier extensive protein-lipid reconstitution studies, the conditions
      under which bacteriorhodopsin forms organised 2D arrays in large unilamellar
      vesicles have been established using freeze-fracture electron microscopy. In a
      background bilayer matrix of phosphatidylcholine (diC(14:0)), the protein can
      form arrays only when the anionic purple membrane lipid, phosphatidylglycerol
      phosphate (or the sulphate derivative) is present. Here we have now extended this
      work to investigate the effect of bilayer thickness on array formation.
      Phosphatidylcholines with various chain lengths (diC(12:0), diC(14:0) and
      diC(16:0)) and which form bilayers of well defined bilayer thickness, have been
      used as the matrix into which bacteriorhodopsin, together with minimal levels (c.
      4-10 lipids per bacteriorhodopsin) of diphytanyl phosphatidyl-glycerol phosphate,
      has been reconstituted. Arrays are formed in all complexes and bhickness appears
      only to alter the type of array formed, either as an orthogonal or as an
      hexagonal array. Secondly, we have previously deduced the entire conformation of
      retinal within the bacteriorhodopsin binding pocket in oriented purple membrane
      fragments. Using solid state deuterium NMR of the specifically deutero-methylated
      retinal labelled at each of the methyl positions in the molecule, the C-CD(3)
      bond vectors of the chromophore have been resolved to +/- 2 degrees . The ring
      conformation is 6-S-trans, but the polyene chain is slightly curved when in the
      protein binding site. Here, we describe studies on the protein in both the ground
      state and the trapped M(412)-state of the photocycle, to show that the
      orientation of the central methyl group (C(19)) on the polyene chain, which is at
      40 degrees +/- 1 degrees with respect to the membrane normal, only changes its
      orientation by approximately 4 degrees upon 13-cis-isomerization. Thus, it is the
      Schiff base end of the chromophore which moves upon light incidence acting as a
      local switch on the protein in the photocycle, whilst the ring end of the
      chromophore moves rather less.

PMID- 17023317
TI  - Evidence for parallel photocycles and implications for the proton pump in
      bacteriorhodopsin.
AB  - In order to account for the large variety of kinetic phenomena in the light
      induced reactions of bacteriorhodopsin's retinal chromophore (BR), a scheme of
      parallel photocycles has been proposed [W. Eisfeld, C. Pusch, R. Diller, R.
      Lohrmann and M. Stockburger, Biochemistry, 32 (1993) 7196-7215]. In the present
      study an experimental test for the validity of this model is described which is
      based on the fact that in the alkaline region the longest-living intermediates
      M(f), M(S) or N in each of the proposed cycles have significantly different
      lifetimes. A condition for the existence of parallel cycles would be that the
      population of M(f), M(S) or N is accompanied by a respective depletion of BR in
      each individual cycle. Dual-beam laser experiments were performed which showed
      that this condition is fulfilled. It is concluded that those proton transfer
      steps which are important for the function as a proton pump are the same for all
      cycles.

PMID- 17023318
TI  - M-decay in the bacteriorhodopsin photocycle: effect of cooperativity and pH.
AB  - The dependence of the bacteriorhodopsin (bR) photocycle on the intensity of the
      exciting flash was investigated in purple membranes. The dependence was most
      pronounced at slightly alkaline pH values. A comparison study of the kinetics of
      the photocycle and proton uptake at different intensities of the flash suggested
      that there exist two parallel photocycles in purple membranes at a high intensity
      of the flash. The photocycle of excited bR in a trimer with the two other bR
      molecules nonexcited is characterized by an almost irreversible M --> N
      transition. Excitation of two or three bR in a trimer induces the N --> M back
      reaction and accelerates the N --> bR transition. Based on the qualitative
      similarity of the pH dependencies of the photocycles of solubilized bR and
      excited dimers and trimers we proposed that the interaction of nonexcited bR in
      trimers alters the photocycle of the excited monomer as compared to solubilized
      bR and the changes in the photocycles in excited dimers and trimers are the
      result of decoupling of this interaction.

PMID- 17023319
TI  - Bacteriorhodopsin: a paradigm for proton pumps?
AB  - Recent studies of the photochemistry of wild type and mutant bacteriorhodopsins,
      their proton release and uptake kinetics, and their X-ray diffraction structure
      have suggested a hypothesis for the way energy is coupled in this light-driven
      proton pump. The first and critical step in converting light energy to a
      vectorial proton potential is the transfer of the Schiff base proton to D85 which
      causes dissociation of the Schiff base-counterion complex. Removal of this
      primarily coulombic interaction destabilizes the protein structure, and results
      in transition to an alternative conformation in which the two proton conduction
      pathways between the active site and the membrane surfaces are reorganized.
      Recovery of the initial charge state of the Schiff base and D85 must therefore
      occur through a series of unidirectional proton transfers that create a
      transmembrane electrochemical proton gradient. Passage of the transported proton
      through the two peripheral protein domains appears to utilize hydrogen bonded
      networks containing aspartate, arginine and bound water. This kind of mutual
      interaction between the active site and the protein conformation that determines
      the conductive pathways to the two membrane surfaces may have relevance to ion
      pumps in general.

PMID- 17023320
TI  - Bacteriorhodopsin mutants D85N, D85T and D85,96N as proton pumps.
AB  - Proton translocation in the BR mutants D85N, D85T and D85,96N was studied by
      attachment of purple membranes to planar lipid bilayers. Pump currents in these
      mutants were measured via capacitive coupling and by use of the appropriate
      ionophores. All mutants have a reduced pK of their Schiff bases around 8-8.5 in
      common. At physiological pH, a mixture of chromophores absorbing at 410 nm
      (deprotonated form) and around 600 nm (protonated form) coexists. Excitation with
      continuous blue light induces in all three mutants an outwardly directed
      stationary pump current. These currents are enhanced upon addition of azide in
      D85N and D85,96N by a factor of 50, but no azide enhancement is observed in D85T.
      Yellow light alone induces transient inwardly directed currents in the mutants
      but additional blue light leads to a stationary current with the same direction.
      All the observed currents are carried by protons, so that the consecutive
      absorption of a yellow and a blue photon leads to inverted stationary
      photocurrents by the mutants, as observed with halorhodopsin (HR). A mechanistic
      model describing the inversion of proton pumping is discussed by the cis-trans,
      trans-cis isomerization of the retinal and the different proton accessibility of
      the Schiff base from the extracellular or the cytoplasmic side of the membrane.

PMID- 17023321
TI  - Introduction of a method for three-dimensional mapping of the charge motion in
      bacteriorhodopsin.
AB  - Electric signals associated with the photocycle of bacteriorhodopsin carry
      valuable information about the proton transport process. Photocurrents measured
      by different experimental methods are interpreted in terms of intramolecular
      charge displacements. Permanent electrical asymmetry of the sample is considered
      to be a prerequisite for the detection of electric signals. The various
      photoelectric measuring techniques can be distinguished by the way of achievement
      of this asymmetry. A common feature of the available methods, however, is that
      the samples are cylindrically symmetric. Consequently, intramembraneous charge
      displacements can normally be monitored only along the axis of the membrane
      normal. We developed a novel method that allows also the detection of the in
      plane components of the charge displacements. Samples containing oriented purple
      membrane fragments were used in the experiments, and the rotational symmetry was
      transiently broken via anisotropic excitation of the bR molecules by linearly
      polarized light. Kinetics of the normal and in-plane components were measured and
      interpreted as a result of spatial charge displacements associated with the
      proton transport process in bacteriorhodopsin.

PMID- 17023322
TI  - Transducer protein HtrI controls proton movements in sensory rhodopsin I.
AB  - Sensory rhodopsin I (SR-I lambda(max) 587 nm) is a phototaxis receptor in the
      archaeon Halobacterium salinarium. Photoisomerization of retinal in SR-I
      generates a long-lived intermediate with lambda(max) 373 nm which transmits a
      signal to the membrane-bound transducer protein HtrI. Although SR-I is
      structurally similar to the electrogenic proton pump bacteriorhodopsin (BR),
      early studies showed its photoreactions do not pump protons, nor result in
      membrane hyperpolarization. These studies used functionally active SR-I, that is,
      SR-I complexed with its transducer HtrI. Using recombinant DNA methods we have
      expressed SR-I protein containing mutations in ionizable residues near the
      protonated Schiff base, and studied wild-type and site-specifically mutated SR-I
      in the presence and absence of the transducer protein. UV-Vis kinetic absorption
      spectroscopy, FT-IR, and pH and membrane potential probes reveal transducer-free
      SR-I photoreactions result in vectorial proton translocation across the membrane
      in the same direction as that of BR. This proton pumping is suppressed by
      interaction with transducer which diverts the proton movements into an
      electroneutral path. A key step in this diversion is that transducer interaction
      raises the pK(a) of the aspartyl residue in SR-I (Asp76) which corresponds to the
      primary proton-accepting residue in the BR pump (Asp85). In transducer-free SR-I,
      our evidence indicates the pK(a) of Asp76 is 7.2, and ionized Asp76 functions as
      the Schiff base proton acceptor in the SR-I pump. In the SR-I/HtrI complex, the
      pK(a) of Asp76 is 8.5, and therefore at physiological pH (7.4) Asp76 is neutral.
      Protonation changes on Asp76 are clearly not required for signaling since the SR
      I mutants D76N and D76A are active in phototaxis. The latent proton-translocation
      potential of SR-I may reflect the evolution of the SR-I sensory signaling
      mechanism from the proton pumping mechanism of BR.

PMID- 17023323
TI  - Bacteriorhodopsin variants as versatile media in optical processing.
AB  - The photochromic properties of bacteriorhodopsin (BR), in addition to its
      longevity and excellent reversibility, are attractive features for the
      construction of light-sensitive media for optical information processing.
      However, the various optical techniques require media with specifically adapted
      and widely differing properties. Genetic engineering of BR and biotechnological
      production of mutated BRs is the key for the utilization of this photochromic
      compound in optical applications. Mutated BRs, generated by single and double
      amino acid exchanges, have been used as recording media for optical applications
      such as phase conjugation or long-term data storage at room temperature.

PMID- 17023324
TI  - Rhodopsin(s) in eubacteria.
AB  - While the biochemical basis of photosynthesis by bacteriochlorophyll-based
      reaction centres in purple phototrophic Eubacteria and retinal-based
      bacteriorhodopsin in the Archaebacterium Halobacterium salinarium has been
      elucidated in great detail, much less is known about photosensory signal
      transduction; this is especially the case for Eubacteria. Recent findings on two
      different photosensory proteins in two different Eubacteria, which both show
      clear resemblances to the rhodopsins, will be presented. The photoactive yellow
      protein (PYP) from the purple phototrophic organism Ectothiorhodospira halophila
      probably functions as the photoreceptor for a new type of negative phototaxis
      response and has been studied in some detail with respect to its structural and
      photochemical characteristics. On basis of crystallographic an photochemical data
      it has been proposed that PYP contains retinal as a chromophore. However, we have
      unambiguously demonstrated that the PYP chromophore is different from retinal, in
      spite of the fact that PYP's photochemical properties show striking similarities
      with the rhodopsins. The cyanobacterium Calothrix sp. displays complementary
      chromatic adaptation, a process in which the pigment composition of the
      phycobilisomes is adjusted to the spectral characteristics of the incident light.
      In orange light the blueish chromophore phycocyanin is present, in green light
      the reddish phycoerythrin is synthesized. On the basis of the action spectrum of
      this adaptation process, we hypothesized that a rhodopsin is the photosensor in
      this process. In line with this, we found that nicotine, an inhibitor of the
      biosynthesis of beta-carotene (which is the precursor of retinal), abolishes
      chromatic adaptation. Direct proof of the involvement of a photosensory rhodopsin
      was obtained in experiments in which the chromatic adaptation response was
      restored by the addition of retinal to the cultures. The two photosensory
      proteins mentioned above represent the first examples of eubacterial
      photoreceptors that can be studied at a molecular level. Our current knowledge on
      these two proteins and their status as retinal proteins will be reviewed.

PMID- 17023325
TI  - Defining control coefficients in non-ideal metabolic pathways.
AB  - The extent to which an enzyme controls a flux has been defined as the effect on
      that flux of a small modulation of the activity of that enzyme divided by the
      magnitude of the modulation. We here show that in pathways with metabolic
      channelling or high enzyme concentrations and conserved moieties involving both
      enzymic and non-enzymic species, this definition is ambiguous; the magnitude of
      the corresponding flux control coefficient depends on how the enzyme activity is
      modulated. This is illustrated with two models of biochemically relevant
      pathways, one in which dynamic metabolite channelling plays a role, and one with
      a moiety-conserved cycle. To avoid such ambiguity, we view biochemical pathways
      in a more detailed manner, i.e., as a network of elemental steps. We define
      'elemental control coefficients' in terms of the effect on a flux of an equal
      modulation of the forward and reverse rate constant of any such elemental step
      (which may correspond to transitions between enzyme states). This elemental
      control coefficient is independent of the method of modulation. We show how
      metabolic control analysis can proceed when formulated in terms of the elemental
      control coefficients and how the traditional control coefficients are related to
      these elemental control coefficients. An 'impact' control coefficient is defined
      which quantifies the effect of an activation of all elemental processes in which
      an enzyme is involved. It equals the sum of the corresponding elemental control
      coefficients. In ideal metabolic pathways this impact control coefficient reduces
      to the traditional flux control coefficient. Differences between the traditional
      control coefficients are indicative of non-ideality of a metabolic pathway, i.e.
      of channelling or high enzyme concentrations.

PMID- 17023326
TI  - Diffusion influenced binary reactive processes in membranes involving identical
      particles: a Monte Carlo study.
AB  - Simple random walk simulations on triangular lattices were performed in order to
      obtain a basic quantitative understanding of the kinetics of diffusion influenced
      binary reactive processes of membrane associated peptides or proteins within the
      two dimensionality of lipid bilayers. The results of the Monte Carlo simulations
      are compared with various formal approximate steady-state approaches, such as
      presented by Keizer [Acc. Chem. Res., 18 (1985) 235-241] in the context of
      statistical nonequilibrium thermodynamics or by Hardt [Biophys. Chem., 10 (1979)
      239-243], based on the well known work of Delbruck and Adam. For diffusion
      controlled binary reactions of identical particles, nice agreement with the
      numerically simulated values is found in the low concentration limit for both
      Hardt's and Keizer's approach. For the latter a fluctuating steady-state particle
      source has to be considered. The dependence of the steady-state rate coefficient
      on system size is investigated, and the results are compared to the work of
      Swartz and Peacock-Lopez [J. Chem. Phys., 95 (4) (1991) 2727-2731]. In order to
      elucidate the results, a practical application is considered. An application to a
      dimerization reaction on vesicles of typical experimental dimensions is given.

PMID- 17023327
TI  - Photoacoustic diagnostics of fast photochemical and photobiological processes.
      Analysis of inverse problem solution.
AB  - Photoacoustic (PA) diagnostics is a time-resolved experimental technique that
      measures transient photoinduced volume changes on the nano- and microsecond time
      scales. The technique has been used to study the energetics and dynamics of
      chemical and biochemical reactions initiated by absorption of light. The dynamics
      of the volume changes and associated relaxation processes can be restored from PA
      waveforms by solving an ill-posed problem of deconvolution. For the systems with
      known relaxation kinetics scheme this problem is usually solved by an iterative
      approximation algorithm. In complex photoactive systems (e.g. photosynthetic
      samples), where information about kinetics of fast photoinduced volume changes is
      not available, an algorithm of direct deconvolution must be used. The
      implementation of one of the linear deconvolution algorithms (Tikhonov's alpha
      regularization) for the PA-diagnostics is therefore considered. The problem of
      the optimal choice of experimental set-up, and restoration algorithm is analyzed
      by a numerical simulation. It is shown that the quality of PA-diagnostic
      experiment is mainly determined by a transfer function converting the relaxation
      spectrum to the spectrum of output electric signal. The analytical expressions to
      calculate this function (so called PA-filter) are presented. The performance of
      two widely used schemes of PA-diagnostics are then directly compared. The time
      resolution of the PA-diagnostics in analysis of simultaneous bi-exponential decay
      is evaluated, and the relationship between the resolving power and parameters of
      the experimental set-up (signal-to-noise ratio, sampling rate, shape of the PA
      filter) is found. The advantage of front face irradiation scheme with
      piezopolymer film detector for time-resolved measurements is demonstrated.

PMID- 17023328
TI  - Effect of headgroup type on the miscibility of homologous phospholipids with
      different acyl chain lengths in hydrated bilayer.
AB  - The miscibility of homologous phosphatidylcholines with different acyl chain
      lengths in hydrated bilayer was examined through the binary phase diagram
      constructed by differential scanning calorimetry. By analyzing the phase diagram
      according to a thermodynamic model based on the Bragg-Williams approximation to
      evaluate the excess free energy of mixing, the non-ideality parameter of mixing,
      rho(0), was estimated, which allows one to interpret the mixing behavior of the
      two lipid components in terms of the difference in the pair-interaction energies
      between like-pairs and mixed-pairs formed in the mixture. By summarizing the
      rho(0) values obtained previously for other classes of phospholipids, it was
      found that rho(0) increases in the order of phosphatidylglycerol (PG)
      approximately phosphatidylcholine (PC) < phosphatidylethanolamine (PE) <
      phosphatidic acid (PA). Since the difference in the pair-interaction energies is
      considered to be determined by the relative contribution of inter-headgroup
      interaction to the overall intermolecular interaction, this sequence of rho(0)
      value suggests that the headgroup interaction in hydrated bilayer increases in
      the order of PA < PE < PC approximately PG.

PMID- 17023330
TI  - Personal recollections.
AB  - I hope that this article will provide a short review of my involvement with
      physical and biological aspects of 'excluded volume' or 'molecular crowding'. The
      list of references is not exhaustive, but is meant primarily to acknowledge my
      debt to my many colleagues.

PMID- 17023331
TI  - An early look at macromolecular crowding.
AB  - Interest in the interaction between proteins and polysaccharides in semidilute
      systems developed in the late 1950's and early 1960's both in the field of matrix
      biology and in the construction of new separation techniques. The author gives an
      account of how his work in the 50's on the characterization of a connective
      tissue polysaccharide, hyaluronan, led him into studies on polysaccharide
      networks, sieve effects, molecular exclusion, a theory of gel filtration,
      solubility of proteins and chemical equilibria in polymer solutions, water and
      protein homeostatis in vivo, and ordered convectional flow in concentrated
      polymer systems.

PMID- 17023332
TI  - Fluctuations and membrane heterogeneity.
AB  - Biological membranes contain many specialized domains, ranging from tens of
      nanometers to several microns in size and characterized by different
      concentrations and compositions of protein. Because these domains influence
      membrane function, considerable attention has focused on understanding their
      origin. Here it is shown that number fluctuations and nonspecific interprotein
      interactions can lead to considerable heterogeneity in the distribution of
      membrane proteins, and to an associated submicron-scale domain structure. Number
      fluctuations were analyzed by modeling the membrane as a two-dimensional fluid
      containing interacting protein solutes. The characteristic size and lifetime of a
      domain in which one would expect to observe a fluctuation of specified magnitude
      was calculated; snapshots showing fluctuation-induced heterogeneity were
      generated by Monte Carlo simulation. Domain size was found to depend on the
      nature of the interprotein force (e.g., attractive or repulsive) and on the
      average protein concentration. Domain size was largest at low protein
      concentrations and in the presence of attractive interprotein forces, and was
      smallest at high protein concentrations and in the presence of repulsive
      interprotein forces. Domain lifetime was found to depend on domain size and on
      the diffusion coefficient of the proteins. In a 'typical' membrane containing 5
      nm proteins with diffusion coefficient 10(-10) cm(2)/s at a density of 1000
      proteins/microm(2), a 30% fluctuation will yield domains characterized by a 2
      fold difference in local concentration; these domains persist over a distance of
      about 100 nm and have a lifetime of about 0.25 s. These results can be used to
      analyze the domain structure commonly observed in electron micrographs, and have
      implications for both number fluctuation and Monte Carlo studies of the
      distribution and dynamics of membrane proteins.

PMID- 17023333
TI  - Measurement of thermodynamic nonideality arising from volume-exclusion
      interactions between proteins and polymers.
AB  - The effective thermodynamic radii of 23 ribosomal proteins from the 50 S subunit
      have been determined by gel chromatography on Sephadex G-50, thereby supporting
      the contention that most of the proteins of the 50 S ribosomal unit exhibit
      reasonably globular structures. To investigate further the usefulness of
      modelling proteins as spheres, the second virial coefficient describing excluded
      volume interactions of some ribosomal proteins with two inert polymers,
      polyethylene glycol (PEG) and dextran, has been determined by gel chromatography
      and/or sedimentation equilibrium techniques. Protein-polymer excluded volumes
      obtained with PEG 20000 and Dextran T70 as the space-filling solute are shown to
      conform reasonably well with a quantitative expression describing interaction
      between an impenetrable sphere and an ideal Brownian path (K.M. Jansons and C.G.
      Phillips, J. Colloid Interface Sci., 137 (1990) 75).

PMID- 17023334
TI  - Brownian dynamics simulation of probe diffusion in DNA: effects of probe size,
      charge and DNA concentration.
AB  - We have used Brownian dynamics simulation to study probe diffusion in solutions
      of short chain DNA using our previously developed simulation algorithm. We have
      examined the effect of probe size, charge, and DNA concentration on the probe
      diffusion coefficient, with the aim of gaining insight into the diffusion of
      proteins in a concentrated DNA environment. In these simulations, DNA was modeled
      as a worm-like chain of hydrodynamically equivalent spherical frictional elements
      while probe particles were modeled as spheres of given charge and hydrodynamic
      radius. The simulations allowed for both short range Lennard-Jones interactions
      and long ranged electrostatic interactions between charged particles. For
      uncharged systems, we find that the effects of probe size and DNA concentration
      on the probe diffusion coefficient are consistent with excluded volume models and
      we interpret our results in terms of both empirical scaling laws and the
      predictions of scaled particle theory. For charged systems, we observe that the
      effects of probe size and charge are most pronounced for the smallest probes and
      interpret the results in terms of the probe charge density. For an ionic strength
      of 0.1 M we find that, below a critical probe surface charge density, the probe
      diffusion coefficient is largely independent of probe charge and only weakly
      dependent on the DNA charge. These effects are discussed in terms of the
      interactions between the probe and the DNA matrix and are interpreted in terms of
      both the underlying physics of transport in concentrated solutions and the
      assumptions of the simulation model.

PMID- 17023335
TI  - Dependence of the biological activity and mass spectrometric pattern on the
      structure peculiarities of the molecule of alkylating drug thiotepa.
AB  - Structural and electronic parameters of the chemotherapeutic alkylating drug
      thiotepa obtained by MNDO and MINDO/3 quantum mechanical calculations are used to
      explain some physical, chemical and biological properties of this compound. On
      the basis of the revealed difference between the preferential conformations of
      the thiotepa molecule in crystal and vacuum, a conclusion is made concerning the
      precautions in the choice of the appropriate molecular geometry in the search of
      structure-activity correlations. The theoretical data are also applied to the
      explanation of some peculiarities of soft ionization mass spectra of thiotepa, in
      particular its sensitivity to high field effects and the absence of protonation.
      The modeling of some reactions of thiotepa directly in the conditions of field
      ionization mass spectrometric experiment is discussed.

PMID- 17023336
TI  - Interaction of calcium ions and polyelectrolytes.
AB  - Interaction of Ca(2+) ions with poly(acrylic acid) (PAA) or poly(methacrylic
      acid) (PMA) was studied using a Ca(2+) ion sensitive electrode. When the PAA
      solution was neutralized with Ca(OH)(2), the Ca(2+) activity had a maximum around
      the degree of neutralization 0.5 and decreased with further increase of
      Ca(OH)(2), being similar to the behavior of the Ca(2+) activity in a maleic acid
      copolymer solution as reported previously. When the polymer concentration was as
      low as 0.1 mM, this peak in the Ca(2+) activity was not observed and the
      counterion condensation theory held. The decrease of the Ca(2+) activity in PAA
      solution at the degree of neutralization unity was depresseed by the presence of
      several millimolar KCl. The Ca(2+) activity in the PAA solution at the low degree
      of neutralization was increased by the presence of dilute KCl and decreased by
      the presence of concentrated KCl. The decrease of the Ca(2+) activity in PMA
      solution was observed also at the degree of neutralization unity, but its extent
      was small compared with that of the PAA solution and the maximum of the Ca(2+)
      activity was shifted to the degree of neutralization 0.75. The effects of KCl on
      the Ca(2+) activity in the PMA solution were almost the same as those in the PAA
      solution. Interpretations of the behavior of the Ca(2+) activity were discussed.

PMID- 17023337
TI  - Simulation of state 4 --> state 3 transition in isolated mitochondria.
AB  - The mathematical dynamic model of oxidative phosphorylation developed previously
      and in the accompanying paper was modified to involve isolated mitochondria
      conditions; it was also used to simulate state 4 --> state 3 transition in rat
      liver mitochondria incubated with succinate as respiratory substrate and glucose
      hexokinase as an ADP-regenerating system. Changes in the respiration rate,
      protonmotive force and reduction level of ubiquinone and cytochrome c as well as
      the internal (i) and external (e) ATP/ADP ratio between state 4 and state 3 were
      calculated and compared with the experimental data. Flux control coefficients
      with respect to oxygen consumption flux for different reactions and processes of
      oxidative phosphorylation were simulated for different values of the respiration
      rate (state 4, state 3 and intermediate states). Flux control coefficients for
      the oxidation, phosphorylation and proton leak subsystems with respect to the
      oxidation, phosphorylation and proton leak fluxes for different values of the
      respiration rate were also calculated. These theoretical data were compared with
      the experimental results obtained in the frame of metabolic control analysis and
      the 'top-down' approach to this analysis. A good agreement was obtained.
      Simulated time courses of the respiration rate, the protonmotive force (Deltap)
      and other parameters after addition of a small amount of ADP to mitochondria in
      state 4 mimicked at least semiquantitatively the experimentally measured time
      courses of these parameters. It was concluded, therefore, that in the present
      stage, the model is able to reflect different properties of the oxidative
      phosphorylation system in a broad range of conditions fairly well, allows deeper
      insight into the mechanisms responsible for control and regulation of this
      process, and can be used for simulation of new experiments, thus inspiring
      experimental verification of the theoretical predictions.

PMID- 17023338
TI  - Conformational study of valinomycin: a molecular dynamics approach.
AB  - Valinomycin is a highly flexible cyclic dodecadepsipeptide that transports ions
      across membranes. Such a flexibility in the conformation is required for its
      biological function since it has to encounter a variety of environments and
      liganding state. Exploration of conformational space of this molecule is
      therefore important and is one of the objectives of the present study that has
      been carried out by means of high temperature Molecular Dynamics. Further, the
      stability of the known bracelet-like structure of the uncomplexed valinomycin and
      the inherent flexibility around this structure has been investigated. The
      uncomplexed form of valinomycin has been simulated at 75-100 K for 1 ns in order
      to elucidate the average conformational properties. An alanine-analog of
      valinomycin has been simulated under identical conditions in order to evaluate
      the effect of sidechain on the conformational properties, The studies confirm the
      effect of sidechain on conformational equilibrium.

PMID- 17023339
TI  - Electrostatic interaction between two charged spherical molecules.
AB  - An explicit analytic expression is obtained for the electrostatic energy of the
      interaction between two ion-impenetrable space-charged hard spheres as a model
      for spherical molecules in an electrolyte solution on the basis of the linearized
      Poisson-Boltzmann equation. An explicit expression for the potential distribution
      in a 3D-space is also found. The polarization effects due to the mutual influence
      between the spheres are taken into account. The analysis is done by assuming
      different dielectric permittivities of the respective spheres and of the solution
      as well. It is shown that the correction terms in the expression for the total
      energy of interaction arising from the polarization effects always correspond to
      forces of attraction between the spheres. The contribution of these terms to the
      total energy of interaction depends on the distance between the two spheres and
      the dielectric permittivities of the spheres and the solution as well as on the
      electrolyte concentration in the solution. A numerical simulation of the
      potential field topography is carried out at several values of the Debye-Huckel
      parameter. It is shown that the polarization effect can produce significant
      changes in the potential distribution in the case of strong interacting spheres.

PMID- 17023340
TI  - Size effects in nonpolar solvation: lessons from two simple models.
AB  - Size dependence of the solute chemical potential mu(u) is examined using the
      Ornstein-Zernike equation for two models of the nonpolar solute-solvent
      interactions. Simple Lennard-Jones interactions are assumed in the first model
      while the Lennard-Jones potential is distributed over the solute volume in the
      second model similar to the Hamaker theory for the colloid dispersion forces. In
      both models, while mu(u) rises asymptotically as the third power of the solute
      size in agreement with asymptotic solution of the scaled particle theory, it
      increases faster at smaller sizes. Deviations from the cubic law are more
      pronounced at higher solvent densities and stronger molecular interactions.
      Within a relatively narrow size range typical for small organic molecules, mu(u)
      can be approximated with a polynomial of the third or even the second power.
      However, the latter approximation is less accurate and cannot be employed for
      extrapolation to the larger size region.

PMID- 17023341
TI  - Fluorescence recovery after photobleaching of suspensions of vacuoles.
AB  - In this work we derive theoretical expressions for the FRAP measured on a liquid
      suspension of vacuoles labelled by a fluorescent probe bound to the surface
      membrane of these vacuoles. The bleaching laser beam creates an inhomogeneity in
      the surface concentration of the probe molecules. We consider the case in which
      the randomization of these probe molecules on the vacuole surface occurs much
      faster than the fluorescent recovery due to the vacuole diffusion. For a given
      value of the bleaching parameter K, we found that the bleaching fraction of the
      fluorescent molecules and the fluorescence recovery rate are decreasing functions
      of the square ratio of the vacuole to the laser beam radius of the FRAP
      instrument.

PMID- 17023342
TI  - Monte Carlo studies on potentiometric titration of (carboxymethyl)cellulose.
AB  - Monte Carlo simulations of the potentiometric titration are carried out for
      (carboxymethyl)cellulose in aqueous salt solutions by a previously developed
      method. A nearly elliptic cylinder with spherical ionizable groups is assumed as
      model of (carboxymethyl)cellulose molecule. The spherical charges with a hard
      core potential are adopted as mobile hydrated ions. A fairly satisfactory
      agreement of the titration curves with the experimental data is achieved by using
      reasonable molecular dimensions. Dependence of the calculated titration profiles
      on the molecular model and the characteristics of the system are discussed.

PMID- 17023344
TI  - Fluorescence correlation spectrometry of the interaction kinetics of
      tetramethylrhodamin alpha-bungarotoxin with Torpedo californica acetylcholine
      receptor.
AB  - Fluorescence correlation spectroscopy (FCS) is suited to determine low
      concentrations (10(-8) M) of slowly interacting molecules with different
      translational diffusion coefficients on the level of single molecule counting.
      This new technique was applied to characterize the interaction dynamics of
      tetramethylrhodamin labelled alpha-bungarotoxin (B( *)) with the detergent
      solubilized nicotinic acetylcholine receptor (AChR) of Torpedo californica
      electric organ. At pseudo-first-order conditions for AChR, the complex formation
      with B( *) is monophasic. The association rate coefficient of the monoliganded
      species AChR . B is k(ass)' = 3.8 . 10(3) s(-1) at 293 K (20 degrees C). The
      dissociation of bound B( *) from the monomer species AChR . B( *) . B (and AChR .
      B(2)( *)), initiated by adding an excess of nonlabelled alpha-bungarotoxin (B),
      is biphasic suggesting a three state cascade for the B-sites: R(alpha) -->
      R(alpha)' --> R(alpha)'' with the exchange dissociation constants: (k(diss)')(B)
      = 5.5(+/-1) . 10(-5) s(-1) and (k(diss)'')(B) = 3(+/-1) . 10(-6) s(-1) at 293 K.
      The data are consistent with dissociative intermediate steps of ligand exchange
      on two different interconvertible conformations of one binding site. The
      dissociation of bound B( *) by excess of the neurotransmitter acetylcholine (ACh)
      is biphasic. At [ACh] = 0.1 M both B( *) are released from the AChR . B(2)( *)
      species. The mechanism involves associative ternary intermediates (AChR . B( *)A,
      AChR . B( *)A(2) and AChR . B(2)( *)A(2)). The equilibrium constants (K(A)) and
      dissociation rate constants (k(-A)) for ACh in the ternary complex state
      R(alpha)' and R(alpha)'', respectively, are K(A)' = 1.1 . 10(-2) M and k(-A)' = 3
      . 10(5) s(-1) and K(A)'' = 7.5 . 10(-2) M and k(-A)'' = 2 . 10(6) s(-1). It is of
      physiological importance that the FCS data indicate that the AChR monomer species
      (M(r) = 290 000), which normally at [ACh] 1 mM only binds one ACh molecule, does
      bind two ACh molecules at [ACh] 0.1 M.

PMID- 17023345
TI  - Measurement and computation of the dipole moment of globular proteins III:
      Chymotrypsin.
AB  - The dipole moments of alpha- and gamma-chymotrypsin are determined experimentally
      using the dielectric constant measuring method. The values thus obtained are
      compared with the results of the electric dichroism measurements for alpha
      chymotrypsins by other investigators. The agreement is reasonably good, if not
      satisfactory. The cause of difference appears to be due to the difficulty of
      finding the correct internal field. The interaction between two neighboring
      dipoles is found to be a minor component of the local fields. Secondly, the
      dipole moment of alpha-chymotrypsin was computed using Protein Data Bases. The
      dipole moment of proteins consists of two major components, the moment due to
      fixed surface charges and the core moment due to polar chemical bonds. The method
      of calculation was described in detail in previous papers. The pK shifts of polar
      side chains were calculated using the methods of Tanford et al. and its
      modification by Warshel et al. The agreement between measured and calculated
      dipole moments is satisfactory.

PMID- 17023346
TI  - Electrooptical analysis of alpha-chymotrypsin at physiological salt
      concentration.
AB  - The electric dichroism of alpha-chymotrypsin has been measured in a buffer
      containing 0.1 M Na(+), 10 mM Mg(2+) and 25 mM Tris-cacodylate pH 7.2. The
      reduced dichroism as a function of the electric field strength can be represented
      by the orientation function for permanent dipoles and is not consistent with the
      orientation function for induced dipoles. After correction for the internal
      directing field, the dipole moment is 1.1 x 10(-27) Cm (+/- 10%), corresponding
      to 340 D, at 20 degrees C. The assignment of the permanent dipole moment is
      confirmed by the shape of the dichroism rise curves, which require two
      exponentials with amplitudes of opposite sign for fitting. The dichroism decay
      time constants measured in the range of temperatures between 2 and 30 degrees C
      indicate a temperature induced change of the structure, which is equivalent to an
      increase of the hydrodynamic radius from r = 26.6 A at 2 degrees C to 28.5 A at
      30 degrees C. Our results demonstrate that electrooptical investigations of
      proteins with a high time resolution can be extended to physiological salt
      concentrations without serious problems by use of appropriate instruments.

PMID- 17023347
TI  - Interfacial charge transport in water-in-oil microemulsions stabilized by ionic
      non-ionic surfactant mixtures.
AB  - Interfacial charge transport and mobility have been studied in system-spanning
      nanodroplet clusters formed in water-in-oil microemulsions stabilized by non
      ionic-ionic surfactant mixtures. An unexpectedly large reduction in the
      counterion mobility was derived from a two-step adsorption process which
      described the Langmuir-plot-like conductivity isotherm remarkably well. It also
      conformed very satisfactorily to mobility data of the sodium bis-2
      ethylhexylsulfosuccinate (AOT) counterion derived from frequency-dependent
      dielectric dispersion measurements with singly dispersed nanodroplets of the same
      system as used with the cluster studies. The activation energy attributed to the
      counterion mobility allowed one to calculate approximately the minimum distance
      between the (positive) counterion in the bulk and the surfactant anion in the
      interface.

PMID- 17023348
TI  - Temperature-, electric field- and solute-induced percolation in water-in-oil
      microemulsions.
AB  - We report investigations on the percolation of the aqueous phase in water-in-oil
      microemulsions, comparing systems stabilized by ionic AOT and non-ionic Igepal
      amphiphiles. First, we briefly review the opposite effect of temperature on the
      two systems and compare electric conductivity with viscosity data. In the second
      part, we show that percolation can be induced by high electric fields resulting
      in a shift of the percolation curve. The electric field measurements allow to
      investigate the dynamics of clustering of the water droplets to form a network of
      percolating channels. We examine the slow build-up and the fast decay of the
      percolating structure, monitoring simultaneously electric conductivity and
      electric birefringence. In the third part we discuss the effect of some solutes
      on the percolation curve, especially of small molecules which act as protein
      denaturants and of native and denatured proteins like methemoglobin, chymotrypsin
      and gelatin. The spectroscopic determination of the dimerization of hemin,
      released from denatured hemoglobin, reflects the incorporation of the hemin
      monomers in the surfactant monolayer. In the gelatin system time resolved
      electric birefringence shows that even at low concentrations it is the
      macromolecule which determines the structure of the aqueous domain. In the
      appendix, a simple estimate of the intrinsic Kerr-constant is given for
      microemulsion droplets deformed in an electric field.

PMID- 17023349
TI  - Temperature dependent intermediate structures during the main phase transition of
      dimyristoyl phosphatidylcholine vesicles a combined iodine laser-temperature jump
      and time resolved cryo-electron microscopy study.
AB  - The kinetics of the main phase transition of dimyristoylphosphatidyl choline
      (DMPC) unilamellar vesicles were investigated in the time range from microseconds
      to seconds. Iodine laser-temperature jump (ILTJ) experiments showed three
      discrete relaxation phenomena. Time resolved cryo-electron microscopy (CEM) was
      applied to produce images of intermediate states typical for the relaxation times
      of lipid vesicles in the micro- to millisecond time window. A careful measurement
      of the rate of temperature decrease observed during the production of vitrified
      lamellae of aqueous samples on a copper grid was performed. The best conditions
      resulted in average rates of cooling of 3 x 10(4) K/s. By comparing the images
      from CEM of DMPC vesicle samples vitrified above, at, and below the phase
      transition temperature a structural model was designed, which explains the
      temperature jump relaxation times in the micro- to millisecond time range by the
      formation and disappearance of coexisting clusters of crystalline, intermediate,
      and fluid lipid areas inside the DMPC bilayers.

PMID- 17023350
TI  - Electrical interactions of membrane active peptides at lipid/water interfaces.
AB  - Vital functions of biological membranes are frequently controlled by amphipathic
      peptides that are associated with the lipid bilayer. The extent of association is
      largely determined by influences encountered at the interface between the aqueous
      and lipid moieties, especially involving electrostatic interactions. A basic
      thermodynamic analysis is presented in terms of a partitioning equilibrium where
      the membrane is treated as a non-ideal solution of peptide molecules in a two
      dimensional lipid solvent. This may then be employed to interpret experimental
      association isotherms (i.e. the ratio of associated peptide per lipid plotted
      versus the free aqueous peptide concentration) in the light of a molecular
      mechanism. Special emphasis is directed towards the evaluation of original
      titration data under most general circumstances when the association can be
      monitored using a suitable linear signal (preferentially an optical one). The
      experimental approaches as well as the merits regarding possible information
      about the underlying structural and functional features are discussed with
      pertinent practical examples.

PMID- 17023351
TI  - Kinetics of liposome disintegration from foam film studies: effect of the lipid
      bilayer phase state.
AB  - The kinetics of interfacial liposome breakdown is investigated in the thin liquid
      film microinterferometric set up of Scheludko et al. Suspensions of small
      unilamellar vesicles of dimyristoylphosphatidylcholine are studied at
      temperatures above and below the temperature of the main gel-liquid crystal first
      order phase transition. The experimentally established time traces of the
      velocity of thinning of foam films are used to estimate the kinetic (rate)
      constants of interfacial liposome disintegration. New and previously established
      data for other lipids are summarized and compared with results from kinetic
      measurements of lipid monolayer formation. The thin film experiments confirm the
      existence of interfacial liposomal aggregates. A change in the kinetic behaviour
      is observed, due to the 'melting' of the hydrophobic tails in the lipid
      aggregates. This may have various consequences of biological and pharmacological
      importance.

PMID- 17023352
TI  - Dynamics of single-stranded DNA in polyacrylamide gels during pulsed field gel
      electrophoresis. A birefringence study.
AB  - The study of the orientation of single-stranded DNA in polyacrylamide gels in
      denaturing conditions has been undertaken by electric birefringence in order to
      determine the mechanism involved in the electrophoretic transport. The presence
      of an overshoot in the birefringence signal, when applying the electric field,
      and the study of the influences of the electric field and of the gel
      concentration on the dynamics show that a mechanism of reptation with elongation
      of the molecule occurs in polyacrylamide gels with low T values. Therefore it is
      suggested that the use of pulsed fields in sequencing electrophoresis is possible
      and can lead to a large increase of the length of the fragments that can be
      sequenced in one single run.

PMID- 17023353
TI  - Electric birefringence of polytetrafluoroethylene particles in agarose gels.
AB  - Electric birefringence studies of strongly elongated, rod-like particles of
      polytetrafluoroethylene (PTFE) in agarose gels show that the negative effect
      observed by semi-diluted aqueous suspensions at low frequencies and at low
      electric field strengths (the so called "anomaly') disappears. The absolute value
      of the low frequency effect increases 3-4 times and the amplitude of modulation
      decreases faster compared to that of the suspensions. This together with
      decreased decay relaxation times in gels make the possibilty that the PTFE
      particles orientation in gels is not due to dipolar but to electrophoretic
      orientation mechanism quite probable. Similar change in the orientation mechanism
      could be expected also for suspensions of higher concentrations. The further
      elucidation of the orientation mechanism using fractions with lower
      polydispersity, broader ranges of experimental conditions (particle
      concentration, ionic strength and composition, electric field strengths,
      frequencies, etc.) could be interest for several fields: colloid electro-optics
      and especially that of concentrated colloids, pulsed field gel electrophoresis of
      DNA (and especially its sinusoidal biased field variant) and of nucleoprotein
      complexes and for the gel research.

PMID- 17023354
TI  - Electric polarization of polyelectrolyte and colloid media: dielectric versus
      electro-optic approach.
AB  - The theories of dielectric dispersion and of electric birefringence as a
      representative of electro-optic methods are considered and it is shown that they
      both depend in a similar way simply on the real part of the complex electric
      polarizability of the macromolecules or the particles. The latter also contains
      the permanent dipole moment. Experimental data on dielectric dispersion, electric
      birefringence and electric light scattering of strongly elongated, rod-like
      poly(tetrafluoroethylene) particles are compared and an attempt is made to extend
      the dielectric dispersion curve to lower frequencies using electric birefringence
      and electric light scattering data. Further, the experimental data on dielectric
      dispersion, electric light scattering, electro-orientation and dipolophoresis for
      the more complicated Escherichia coli particles are compared. Again, the
      possibility to extend the 10 kHz-100 MHz dielectric dispersion curve down below 1
      Hz by using electric light scattering data is examined. The good matching of the
      dielectric dispersion and electric light scattering frequency curves found in the
      overlapping frequency range (10 kHz-5 MHz) essentially enhances the chance that
      dielectric dispersion below 1 MHz is related to alpha dispersion and not to
      electrode polarization. Thus it is not only possible to obtain additional
      information on the mechanism of polarization at lower-frequency dielectric
      dispersion, but also to extend our knowledge about the effective dielectric
      properties of biological complex fluids to frequencies essentially below 1 MHz.
      This could be important for the understanding of the effect of low-frequency
      electromagnetic fields on living matter.

PMID- 17023355
TI  - Transient electric birefringence of colloidal particles immersed in shear flow.
      Part II. The initial response under the action of a rectangular electric pulse
      and the behavior at a low alternating electric field.
AB  - The time-dependent rotational diffusion equation for rigid macromolecules in
      solution has been approximately solved for two cases in order to extend the
      electric birefringence technique to streaming-electric birefringence. One is for
      the initial period through the application of a rectangular electric pulse to the
      solution immersed in a low shear flow. The purpose of this is expansion of the
      distribution function into a function series made by the product of the powers of
      reduced time (= Thetat) and hydrodynamic field alpha (= G Theta , G: velocity
      gradient, Theta: rotary diffusion constant) and a surface harmonic P(i)(j)cos
      jphi. The solution for the build-up process at arbitrary electric field strength
      is found, but is limited to low hydrodynamic fields. The other is for the
      response when an alternating electric field is applied to the solution in a shear
      flow. Here, instead of reduced time, the maximum electric field E(0) is chosen as
      a parameter for the expansion. The expressions for the intensity of the
      transmitted light through crossed Nicols are derived in two optical systems where
      the polarizer is set at an angle of 45 degrees and 0 degrees to the direction of
      the electric field. The results in the former case show that we can determine
      four parameters, the ratio of velocity gradient to rotary diffusion constant, the
      axial ratio of a particle, the anisotropy of electric polarizability, and the
      optical anisotropy factor, from four values observed in two optical systems,
      namely, two light intensities before applying an electric field and two initial
      slopes of the build-up after applying an electric field. On the other hand, when
      a low alternating electric field with extremely high frequency is applied, the
      build-up of the light intensity in the former case is the same as that of
      electric birefringence for pure induced dipole orientation. The build-up for the
      latter optical system is the same as the expression for pure induced dipole
      orientation of Eq. (38) shown in a previous work.

PMID- 17023357
TI  - Ligand binding isotherm for DNA in the presence of supercoil-induced non-B form:
      a theoretical analysis.
AB  - A binding isotherm in the form of a modified McGhee-Von Hippel equation is
      proposed, on the basis of thermodynamical considerations, to include the non
      cooperative binding of extended ligands to supercoiled DNA, where a stretch of
      non-B form may be present under superhelical stress. It is then studied, on the
      basis of a non-linear Scatchard plot, how the presence of an intercalating ligand
      can relax the supercoiled molecule and thus destabilise the non-B stretch, which
      may be recognised by the existence of a significant kink in the Scatchard plot.

PMID- 17023358
TI  - Photophysics of the single tryptophan residue in Fusarium solani Cutinase:
      evidence for the occurrence of conformational substates with unusual fluorescence
      behaviour.
AB  - The single tryptophan residue, at position 69 in the amino acid sequence, was
      used as an intrinsic probe to obtain structural and dynamical information on the
      lipolytic enzyme Fusarium solani cutinase. In the enzyme's native state the
      tryptophan fluorescence is highly quenched. Time-resolved experiments reveal that
      the majority of the excited state species is characterized by an unusually fast
      decay time of approximately 40 ps, indicating the occurrence of a very efficient
      nonradiative relaxation process, possibly via the adjacent disulphide bond or via
      the peptide bonds of a nearby loop. A minority of the excited state species
      relaxes on a nanosecond time scale. Irradiation of the enzyme in the tryptophan
      absorption band causes an increase by an order of magnitude of the fluorescence
      quantum yield. This increase is ascribed to a photo-induced, subtle structural
      change of a minor subset of species whose fluorescence is not highly quenched.
      The structural change is accompanied by a tightening of the local environment of
      the tryptophan moiety, as indicated by results from time-resolved fluorescence
      anisotropy which reveal a complete disappearance of the segmental flexibility of
      the tryptophan moiety.

PMID- 17023359
TI  - Surface areas and packing constraints in POPC C (12)EO (n) membranes. A time
      resolved fluorescence study.
AB  - The surface area occupied by nonionic detergents of the type C(12)EO(n) (n = 1-8)
      in POPC C (12)EO (n) mixed membranes was studied by means of time-resolved
      resonance energy transfer (RET) between the fluorescent probe molecules NBD-PE
      and rhodamine-PE. The area data were interpreted within the frame of
      Israelachvili's concept of packing constraints yielding the critical packing
      parameter, f, as a measure of the asymmetry of the molecular shape of the
      membrane constituents. The asymmetry of the molecular shape of the detergent
      increases with the ethylene oxide chain length and correlates with the potency of
      the detergent to solubilize the bilayers and the reduction of the DPH order
      parameter. For n = 1-3, the membrane surface was found to expand by 0.25-0.30
      nm(2) per incorporated C(12)EO(n) molecule. This value corresponds to the cross
      section of one hydrocarbon chain in liquid-crystalline phases. On increasing n
      from n = 4 to n = 8 the net area per detergent molecule increases from 0.43 nm(2)
      to 1.16 nm(2). These surface requirements are consistent with a disordered,
      coiled conformation of the EO-chains hydrated with up to two water molecules per
      ethylene oxide unit. For n > 5 the limiting mole fraction of the bilayer
      saturation was deduced from the f-data in the two-component bilayer. DPH and NBD
      PE fluorescence lifetime data are discussed to give an indication of the
      accessibility of the probe environment to water molecules.

PMID- 17023360
TI  - A stochastic model for the sigmoidal behaviour of cooperative biological systems.
AB  - A stochastic model for cooperative transitions in biological systems based on a
      Markov chain is proposed. This model requires only two parameters, the mean
      probability, p, and the coupling capacity, Deltap, which measure the probability
      of forming a new weak bond depending on the number of similar bonds already
      formed and it is also responsible for the transition. In this paper we show how
      the model works for a large number of identical molecules and how it can be
      useful for studying the noise around the centre of the transition where,
      increasing the degree of cooperativity, i.e. the number n in the well-known Hill
      equation, the width of the noise increases along with its fractal dimension. A
      simple relationship between the degree of cooperativity and the parameter Deltap
      is proposed, suggesting that the cooperativity of real biological transitions is
      related to the coupling capacity Deltap of the present model.

PMID- 17023361
TI  - Evidence for a free radical chain mechanism in the reaction between peroxidase
      and indole-3-acetic acid at neutral pH.
AB  - The oxidation of indole-3-acetic acid (IAA) catalyzed by horseradish peroxidase
      (HRP) in the absence of added H2O2 was studied at pH 7.4 using spectral and
      kinetic approaches. Upon addition of a hundred-fold excess of IAA to HRP the
      native enzyme was rapidly transformed to compound II (HRP-II). HRP-II was the
      predominant catalytic enzyme species during the steady state. No compound III was
      observed. HRP-II was slowly transformed to the stable inactive verdohemo-protein,
      P-670. A precursor of P-670, so-called P-940 was not detected. After the
      cessation of IAA oxidation there was neither oxygen consumption nor P-670
      formation; the remaining HRP-II was spontaneously reduced to native enzyme.
      Single exponential kinetics were observed in the steady state for IAA oxidation,
      oxygen consumption and P-670 formation yielding identical first order rate
      constants of about 6 . 10(4) s(-1). A comparison of the rate of IAA oxidation by
      HRP-II in the steady state and in the transient state indicated that more than 1
      3 of the IAA was oxidized non-enzymatically during the steady state, confirming
      that a free radical chain reaction is involved in the peroxidase-catalyzed
      oxidation of IAA. IAA oxidation stopped before IAA was completely consumed, which
      cannot be ascribed to enzyme inactivation because 30-50% of the enzyme was still
      active after the end of the reaction. Instead, incomplete IAA oxidation is
      explained in terms of termination of the free radical chain reaction. Bimolecular
      rate constants of IAA oxidation by HRP-I and HRP-II determined under transient
      state conditions were (2.2 +/- 0.1) x 10(3) M(-1) s(-1) and (2.3 +/- 0.2) x 10(2)
      M(-1) s(-1).

PMID- 17023362
TI  - Small angle neutron scattering from lysozyme solutions in unsaturated and
      supersaturated states (SANS from lysozyme solutions).
AB  - Small angle neutron scattering (SANS) method was used to study lysozyme
      solutions, with particular interest in an understanding of the crystallization
      process at the initial stage. It is found that (1) in the unsaturated solution,
      the protein molecules aggregate with a continuous increase in size when NaCl
      concentration is increased, and (2) in the supersaturated solution, an
      irreversible change, superimposed on the former process, occurs when the
      supersaturation is realized. These facts indicate the usefulness of SANS in
      detecting changes of protein molecules in solution on the nanometer scale. The
      reliability of the SANS results are indicated by (1) comparing them with those of
      small angle X-ray scattering (SAXS), and (2) comparing the effect of D(2)O and
      H(2)O as solvent. Since the interparticle interaction is essential in the
      crystallization process and a simple Guinier plot analysis is not allowed, a more
      rigorous framework of analyzing data with interference function is developed,
      through which both average interparticle distance and particle size are
      estimated.

PMID- 17023363
TI  - Transition from molecular chaos to coherent spiking of enzymic reactions in small
      spatial volumes.
AB  - Theoretical study of an irreversible enzymic reaction with allosteric product
      activation reveals that, in small spatial volumes, it can undergo a transition to
      coherent spiking regime characterized by the presence of strong correlations
      between reaction events and the states of individual enzyme molecules.

PMID- 17023365
TI  - Birth of the macromolecule.
AB  - The science of chemistry has made considerable advances over the last few hundred
      years in the characterization of "small" molecules which can be purified and
      studied by melting, distillation, crystallization and solubility in various
      liquids. When the study of "large" natural and biological molecules, limited in
      these properties, rose in significance at the turn of the century, it was first
      attempted to explain their properties by the concepts of colloid chemistry of
      aggregation and complex formation. The struggle for the acceptance of the concept
      of the natural or biological covalently bonded macromolecule, as recalled by
      Herman Mark, is one of the interesting chapters in recent science history. A
      specific phase in the establishment of the macromolecular concept centered around
      the development by The Svedberg of the analytical ultracentrifuge, a versatile
      tool of highly practical and profound thermodynamic significance.

PMID- 17023366
TI  - Comparative thermodynamic elucidation of the structural stability of thermophilic
      proteins.
AB  - Differential scanning calorimetry, circular dichroism, and visible absorption
      spectrophotometry were employed to elucidate the structural stability of
      thermophilic phycocyanin derived from Cyanidium caldarium, a eucaryotic organism
      which contains a nucleus, grown in acidic conditions (pH 3.4) at 54 degrees C.
      The obtained results were compared with those previously reported for
      thermophilic phycocyanin derived from Synechococcus lividus, a procaryote
      containing no organized nucleus, grown in alkaline conditions (pH 8.5) at 52
      degrees C. The temperature of thermal unfolding (t(d)) was found to be comparable
      between C. caldarium (73 degrees C) and S. lividus (74 degrees C) phycocyanins.
      The apparent free energy of unfolding (DeltaG([urea]=0)) at zero denaturant
      (urea) concentration was also comparable: 9.1 and 8.7 kcal/mole for unfolding the
      chromophore part of the protein, and 5.0 and 4.3 kcal/mole for unfolding the
      apoprotein part of the protein, respectively. These values of t(d) and
      DeltaG([urea]=0) were significantly higher than those previously reported for
      mesophilic Phormidium luridum phycocyanin (grown at 25 degrees C). These findings
      revealed that relatively higher values of t(d) and DeltaG([urea]=0) were
      characteristics of thermophilic proteins. In contrast, the enthalpies of
      completed unfolding (DeltaH(d)) and the half-completed unfolding (DeltaH(d)) 1 2
      for C. caldarium phycocyanin were much lower than those for S. lividus protein
      (89 versus 180 kcal/mole and 62 versus 115 kcal/mole, respectively). Factors
      contributing to a lower DeltaH(d) in C. caldarium protein and the role of charged
      groups in enhancing the stability of thermophilic proteins were discussed.

PMID- 17023368
TI  - Emergent properties of coupled enzyme reaction systems 1. Switching and
      clustering behaviour.
AB  - The dynamics of locally and globally coupled cells that convert a substrate to a
      product via an uncompetitive substrate-inhibition mechanism is studied. When the
      cell-cell coupling strength is below a threshold value, the coupled system
      exhibits a large number of steady states; however, all cells cluster to one state
      when coupling exceeds the threshold value. The coupled system also exhibits a
      buffering capacity that maintains low and almost constant intracellular and
      extracellular substrate levels; however, there exists a threshold value on the
      influx rate of extracellular substrate beyond which the system switches to higher
      substrate levels. This transition becomes sharper as the number of coupled cells
      increases. Propagation failure of concentration fronts between adjacent cells is
      also exhibited by the system.

PMID- 17023369
TI  - Change in electric characteristics of membranes in response to taste stimuli with
      increasing amount of lipids in membrane matrix of PVC and plasticizer.
AB  - Changes in membrane electric potential in response to taste substances were
      studied for membranes containing differing amounts of negatively charged lipids
      in the membrane matrix of polyvinyl chloride and plasticizer. Responses to
      quinine showing bitterness decreased systematically with increasing the quantity
      of charged lipids contained in the membrane, whereas the response did not depend
      on differences in the hydrocarbon chains of lipids. The mechanism is discussed
      qualitatively in terms of hydrophobicity and hydrophilicity of the membranes.

PMID- 17023370
TI  - Theory of multivalent binding in one and two-dimensional lattices.
AB  - Ligand binding to a linear lattice composed of N sites, under general conditions
      of cooperativity and number of sites covered upon binding, m, is approached in
      terms of the theory of contracted partition functions. The partition function of
      the system obeys a recursion relation leading to a generating function that
      provides an exact analytical solution for any case of interest. Site-specific
      properties of the lattice are derived from simple transformations of the
      analytical expressions. The McGhee-von Hippel model is obtained as a special case
      in the limit N --> infinity. The derivation is straightforward and involves no
      combinatorial arguments. Partition functions and site-specific properties are
      also derived for the case of non-cooperative binding to a two-dimensional torus
      of length N, containing s sites in its section for a total of sN sites. The torus
      provides a relevant model for ligand binding to double-stranded DNA (s = 2) or
      protein helices (s = 3,4). It is proved that non-cooperative binding to the two
      dimensional torus can mimic cooperative binding to a one-dimensional linear
      lattice when m = s. The dimensional embedding of the lattice and the geometry of
      interaction of its sites play a crucial role in defining the binding properties
      of the system accessible to experimental measurements. Hence, caution must be
      exercised in the interpretation of Scatchard plots in terms of the one
      dimensional McGhee-von Hippel model, especially when m < or = 4 and the geometry
      of the system is clearly two-dimensional.

PMID- 17023371
TI  - Map analysis of ligand binding to a linear lattice.
AB  - A one-dimensional mapping of the binding properties of a linear lattice offers an
      exact analytical solution for the site-specific properties of the lattice once
      the length N and the parameter for nearest neighbor interactions are specified.
      The solution is derived independent of the definition of the partition function
      or the transfer matrix, nor does it involve combinatorial arguments. This result
      provides a simple and effective way of analyzing experimental data for protein
      ligand interactions and broadens our understanding of site-specific properties in
      biological macromolecules.

PMID- 17023372
TI  - Thermodynamics of amino acid side-chain internal rotations.
AB  - The absolute Gibbs energy, enthalpy and entropy of each of the internal rotations
      found in protein side chains has been calculated. The calculation requires the
      moments of inertia of the side chains about each bond, the potential energy
      barrier and the symmetry number and gives the maximum possible thermodynamic
      consequences of restricting side chain motion when a protein folds. Hindering
      side chain internal rotations is unfavourable in terms of Gibbs energy and
      entropy; it is enthalpically favourable at 0 K. At room temperature, it is
      estimated that the adverse entropy of hindering buried side chain internal
      rotation is only 25% of the absolute entropy. The difference between absolute
      entropies in the folded and unfolded states gives the entropy change for folding.
      The estimated Gibbs energy change for restricting each residue correlates
      moderately well with the probability of that residue being found on the folded
      protein surface, rather than in the protein interior (where motion is
      restricted).

PMID- 17023373
TI  - R-phycoerythrins having two conformations for the same aggregate.
AB  - The visible circular dichroism (CD) spectrum of an R-phycoerythrin (Porphyra
      tenera) is composed of several positive bands. The protein in aqueous buffer very
      slowly exhibits changes in the CD spectrum of its chromophores, a band at 489 nm
      undergoes an increase in intensity and a red shift. When the band reached a 493
      nm maximum, the spectrum became very stable. The aggregation state of the protein
      did not change during this spectral conversion. The chromophore CD spectrum was
      also obtained in the presence of a low concentration of urea or sodium
      thiocyanate, and the identical change in the CD was noted, but the change was
      much faster. The visible absorption and CD in the far UV spectra were unaffected
      by urea. Unchanged visible absorption and protein secondary structure (61% alpha
      helix) contradicted by comparatively salient alterations in the visible CD
      spectra suggested very subtle structural changes are influencing some of the
      chromophores. For a second R-phycoerythrin (Gastroclonium coulteri), the CD of
      the chromophores had a negative band on the blue edge of the spectrum. This is
      the first negative CD band observed for any R-phycoerythrin. Treatment of this
      protein with low concentrations of urea produced a change in the visible CD with
      the negative band being completely converted to a positive band. Fluorescence
      studies showed that the treatment by urea did not affect energy migration.
      Deconvolution of the CD spectra were used to monitor the chromophores. The
      results demonstrated that the same aggregate of each R-phycoerythrin could exist
      in two conformations, and this is a novel finding for any red algal or
      cyanobacterial biliprotein. The two forms of each protein would differ in
      tertiary structure, but retain the same secondary structures.

PMID- 17023374
TI  - Low-temperature stress induces transient oscillations in sucrose metabolism in
      Solanum tuberosum.
AB  - Exposure to low but nonfreezing temperatures induces the net breakdown of starch
      and the accumulation of sucrose, glucose and fructose in potato tuber tissue, a
      complex phenomenon known as low-temperature sweetening (LTS). When transferred to
      4 degrees C storage, tissue sucrose levels in LTS-sensitive potato tubers
      (Solanum tuberosum cv. Norchip) did not change monotonically to a new steady
      state, but rather transiently oscillated about the trajectory to the new steady
      state. The dynamic patterns observed in sensitive tubers grown in 1993 and 1994
      were qualitatively similar. Quantitatively, however, the transient oscillation
      had a period of 11.5 days in 1993, whereas a period of 80 days was observed in
      1994. In contrast, the sucrose levels of the LTS-tolerant potato tubers (Solanum
      tuberosum seedling ND860-2) increased monotonically to a higher level upon
      exposure to low temperatures.

PMID- 17023376
TI  - Back pain and backpacks in children: biomedical or biopsychosocial model?
AB  - Public press, professional organisations and journals have been sending alarming
      messages about the rising prevalence of back pain in school age children.
      Carrying backpacks has been suggested as one of the key factors contributing to
      back pain in children. The basic assumption based on the biomedical model is that
      the maturing spine cannot handle the mechanical load of the backpack
      sufficiently. A review of the evidence in the professional literature, however,
      revealed very limited evidence to support this assumption. On the contrary, the
      literature does suggest that psychological and social factors may be of greater
      importance to explain back pain in children. We conclude this clinical commentary
      postulating that the public, children and their parents are better served with a
      more modest and balanced perspective of the professionals, and propose that back
      pain in children (as it is in adults) should be viewed from a biopsychosocial
      model.

PMID- 17023377
TI  - Validity and reproducibility of the Jamar dynamometer in children aged 4-11
      years.
AB  - PURPOSE: Validity and reproducibility of the Jamar dynamometer were evaluated in
      children aged 4-11 years. METHOD: Hand grip strength was measured on the dominant
      side and non-dominant side in 67 patients who had been referred to our specialist
      centre in the past 3 years because of suspected myopathy. All the patients had
      had muscle biopsy. Sixteen out of the 67 patients proved to have myopathy, while
      51 had no myopathy. The investigator was blinded against the true diagnosis and
      clinical course of the patients at the time of testing. Validity was assessed by
      the power to discriminate between patients with and without myopathy, using
      logistic regression analysis and receiver operating characteristic (ROC)
      analysis. The area under the ROC curve (AUC) was calculated as a measure of the
      discriminative power. Sensitivity (Se) and specificity (Sp) were assessed at a
      specifically chosen cut-off point. Reproducibility was assessed by evaluating the
      test-retest reliability in a stratified random sample of 40 patients who returned
      for remeasurements, using the intraclass correlation coefficient (ICC). RESULTS:
      AUCs ranged from 0.78 - 0.82. At an Se = 81% cut-off point, Sp varied from 67
      73%. ICCs ranged from 0.91-0.93. CONCLUSIONS: The Jamar dynamometer had
      discriminative power in children with suspected myopathy. Reproducibility was
      high. The Jamar dynamometer was a good, but not completely accurate, test for
      myopathy.

PMID- 17023379
TI  - Introduction: Older adults in medical education--senior mentor programs in U. S.
      medical schools.

PMID- 17023380
TI  - The Senior Mentor Program at the University of South Carolina School of Medicine:
      an innovative geriatric longitudinal curriculum.
AB  - This paper describes development, implementation, and evaluation strategies of a
      longitudinal geriatric curriculum, the Senior Mentor Program (SMP). The rationale
      for exposing undergraduate medical students to healthy, community-dwelling older
      adults is to use the relationship and activities as vehicles for improving
      knowledge of aging and providing students experience with aging as a stage and
      process. The University of South Carolina School of Medicine's major aim in
      geriatrics is to prepare students to become skilled physicians in care of older
      adults. The SMP is embedded into the curriculum. The program introduced medical
      students to healthy older adults, presented selected health care issues in this
      population, integrated material early in the curriculum, acquainted students with
      longitudinal patient care, and introduced students to older adults' living
      arrangements. The SMP is an effective means of infusing geriatric content into
      the medical school curriculum and positively affects mentors' and students'
      attitudes toward each other. This has implications for medical and professional
      schools, such as nursing, social work, and physical therapy.

PMID- 17023381
TI  - Student Senior Partnership Program: University of California Irvine School of
      Medicine.
AB  - The Student Senior Partner Program (SSPP) forms the core of the required medical
      student geriatrics curriculum at the University of California-Irvine School of
      Medicine (UCISOM). The program utilizes a longitudinal modular format that
      extends over the first three years of medical school. Instruction is presented in
      didactic, patient interactive, and facilitated small group discussion sessions.
      Initial educational outcomes have been positive. Ongoing challenges include
      faculty recruitment and retention, recruiting a group of senior partners that
      reflects the diversity of the community, and managing generational and ethno
      cultural conflicts. The program offers unique opportunities for innovative
      development in geriatrics education.

PMID- 17023382
TI  - Evaluating the effectiveness of a Senior Mentor Program: the University of
      Missouri-Columbia School of Medicine.
AB  - At the University of Missouri-Columbia School of Medicine, we developed a
      voluntary senior-mentor program, the Senior Teacher Educator Partnership (STEP),
      for first- and second-year medical students. Using qualitative research methods,
      we examined the impact of STEP on medical students' attitudes and then assessed
      the congruence of what is learned through STEP with the knowledge, skills, and
      attitudes needed to provide care to the elderly patient. STEP was found to be a
      successful strategy for teaching themes of recognizing the elderly within an
      ecological context, enhancing sympathy and empathy, emphasizing respect for
      elderly persons, and gaining an appreciation that aging is an individualized
      process. New areas identified for student learning experiences included
      understanding the complexity of the health care system and its impact on elderly
      patients, understanding the payment system, and developing skills in assessment
      and care coordination. A model is described for continuous enhancement of
      educational programs to be used to improve educational experience in geriatrics.

PMID- 17023383
TI  - The Senior Mentor Program at Duke University School of Medicine.
AB  - The Duke University School of Medicine has a unique curriculum in which students
      complete basic sciences in year 1 and clinical clerkships in year 2, making way
      for an entire year of independent study in year 3. Into this compact curriculum,
      education in geriatrics has been successfully introduced through focused
      exercises and activities strategically integrated in all four years. The most
      popular of these educational strategies is the Senior Mentor Program (SMP),
      through which second year students meet with a senior volunteer from the
      community. In addition to improving students' knowledge and skills in geriatric
      assessment, a central goal of the SMP is to increase students' appreciation for
      the heterogeneity of health and function among the older adult population.
      Students meet one-on-one with their senior mentor to practice communication
      skills and performance of key components of geriatric assessment. Afterward,
      students convene in small groups with division faculty to debrief. Successful
      implementation of the program has required a combination of rigorous logistical
      management and communication with key stakeholders. The program has spawned a
      number of different benefits beyond the curriculum, including faculty development
      in teaching skills and enhanced relationships with individuals and agencies from
      the community. We aspire to continue to improve the structure and content of the
      program to reflect the socioeconomic and ethnic diversity of the community and to
      offer students a longitudinal experience.

PMID- 17023384
TI  - The University of Arizona College of Medicine Optimal Aging Program: stepping in
      the shadows of successful aging.
AB  - The Optimal Aging Program (OAP) at the University of Arizona, College of Medicine
      is a longitudinal mentoring program that pairs students with older adults who are
      considered to be aging successfully. This credit-bearing elective was initially
      established in 2001 through a grant from the John A. Hartford Foundation, and
      aims to expand the concept of aging to include those of active, independently
      living, healthy older adults. The program goals are to provide students with the
      opportunity to develop a relationship with an older adult who continues to be
      active in her community and expand students' concepts of aging to include the
      increasing reality of healthy, active older adulthood. A review of students'
      journals, verbal feedback, and questionnaire surveys has been used to evaluate
      the OAP, and has resulted in minor modifications of the program since inception.
      These findings and the program modifications are described in the present study.
      "Success factors" are identified that may be employed by others attempting to
      develop such programs.

PMID- 17023385
TI  - From aging . . . to saging- the Ohio State Senior Partners Program: longitudinal
      and experiential geriatrics education.
AB  - Ohio State College of Medicine began its Senior Partners Program (SPP) in 2001 as
      part of its commitment to integrate geriatric education throughout all four years
      of the medical curriculum. For participating senior partners and medical
      students, the SPP has signified a journey through a continuum of aging. Initial
      evaluations suggest that students have gained appropriate knowledge, skills, and
      attitudes to care for seniors responsively and cost effectively. Perhaps most
      important is the attitude change that this experience has brought about in the
      students, who are now substituting the health model for the traditional disease
      model of aging, and who have learned to lay aside their stereotypes of aging.
      Student debriefings and faculty evaluations indicate improved learning of
      geriatric skills and knowledge associated with the SPP. Ongoing program
      modification and evaluation will help guide Ohio State's next steps in geriatrics
      education.

PMID- 17023386
TI  - A partnership between the University of Nebraska College of Medicine and the
      community.
AB  - Over the last 20 years, older people have served as teachers for students as part
      of the formal curriculum in geriatrics at the University of Nebraska Medical
      Center. In recent years, we have supported a more in-depth, longitudinal
      experience that connects medical students with elders in the community. The
      program was initiated as a special project of our Aging Interest Group and is
      called the Senior Companionship Program (SCP). Although the SCP is optional, when
      combined with the required experiences for medical students, it triples the
      contact time that students have with older adults in community settings. The
      student-run SCP is fostering positive attitudes towards older adults. Comments
      from participating students indicate that the SCP is a valuable experience, and
      well worth their time commitment. We describe the program structure, changes to
      the program based upon the input of participants, as well as the program's
      strengths, limitations, and prospects.

PMID- 17023387
TI  - The Medical College of Wisconsin Senior Mentor Program: experience of a lifetime.
AB  - The Medical College of Wisconsin (MCW) Senior Mentor Program (SMP) has been
      offered to a small group of first and second year medical students as a course
      alternative to the traditional physician mentor program. The program links
      students with healthy older adult mentors and includes mentor/student visits,
      didactic sessions, written assignments, and shadowing experiences. The goals of
      the course are to increase positive attitudes about aging and geriatrics and to
      teach basic assessment and interviewing skills in geriatric content areas. A
      course evaluation including questionnaires, focus groups, and content analysis
      found that students experienced positive attitude change about geriatric patient
      care, increased knowledge about geriatrics, and satisfaction with the
      mentor/student relationship. Students have reported gains in their knowledge of
      geriatric and gait assessment, ADL evaluation, and mental health screening, among
      other issues. Further, students report being excited, more comfortable, and less
      fearful caring for and interacting professionally with older adults as a result
      of the SMP. The SMP is an effective and meaningful method of geriatric education
      for preclinical students. It may be an alternative at medical schools that cannot
      support a large-scale multi-year senior mentor program.

PMID- 17023388
TI  - Autoregulation of glial cell line-derived neurotrophic factor expression:
      implications for the long-lasting actions of the anti-addiction drug, Ibogaine.
AB  - We recently showed that the up-regulation of the glial cell line-derived
      neurotrophic factor (GDNF) pathway in the midbrain, is the molecular mechanism by
      which the putative anti-addiction drug Ibogaine mediates its desirable action of
      reducing alcohol consumption. Human reports and studies in rodents have shown
      that a single administration of Ibogaine results in a long-lasting reduction of
      drug craving (humans) and drug and alcohol intake (rodents). Here we determine
      whether, and how, Ibogaine exerts its long-lasting actions on GDNF expression and
      signaling. Using the dopaminergic-like SHSY5Y cell line as a culture model, we
      observed that short-term Ibogaine exposure results in a sustained increase in
      GDNF expression that is mediated via the induction of a long-lasting
      autoregulatory cycle by which GDNF positively regulates its own expression. We
      show that the initial exposure of cells to Ibogaine or GDNF results in an
      increase in GDNF mRNA, leading to protein expression and to the corresponding
      activation of the GDNF signaling pathway. This, in turn, leads to a further
      increase in the mRNA level of the growth factor. The identification of a GDNF
      mediated, autoregulatory long-lasting feedback loop could have important
      implications for GDNF's potential value as a treatment for addiction and
      neurodegenerative diseases.

PMID- 17023390
TI  - Induction of a gene expression program in dendritic cells with a cross-linking
      IgM antibody to the co-stimulatory molecule B7-DC.
AB  - While bivalent antibodies can block ligand-receptor interactions, IgM pentamers
      efficiently cross-link cell surface targets and evoke physiological responses. We
      have described one such interaction between an IgM antibody (Ab) and the B7-DC
      costimulatory molecule expressed by dendritic cells that induces strong antitumor
      immunity and modulates pathogenic responses associated with allergic asthma.
      Progressive changes in gene expression in dendritic cells activated by an IgM B7
      DC cross-linking Ab resulted in the increased expression in 350 genes and
      decreased expression of more than 200 genes over the course of 24 h following Ab
      treatment. In particular, up-regulation of the caspase inhibitor FLIP and the
      chemokine receptor CCR7, and the down-regulation of the CXCR4 receptor provide a
      mechanistic basis of Ab-induced survival and enhanced migration into draining
      lymph nodes. Increased expression of both cell surface and secreted molecules
      known to be mediators of the immunomodulatory properties of dendritic cells was
      detected at both the levels of RNA and protein expression. This analysis
      documents the ability of IgM Ab to activate a gene expression cascade leading to
      important biological changes in cellular function and provides mechanistic
      insight into the potent immunomodulatory properties attributed to this Ab.

PMID- 17023389
TI  - Shunting of prostanoid biosynthesis in microsomal prostaglandin E synthase-1 null
      embryo fibroblasts: regulatory effects on inducible nitric oxide synthase
      expression and nitrite synthesis.
AB  - Microsomal prostaglandin (PG) E synthase (mPGES)-1 is an inducible enzyme that
      acts downstream of cyclooxygenase (COX) and specifically catalyzes the conversion
      of prostaglandin (PG)H2 to PGE2, most prominently in inflammatory conditions.
      Specific inhibitors of mPGES-1 are not yet available, however, mice with genetic
      deletion of mPGES-1 have been generated that have given insight into the specific
      role of mPGES-1 in eicosanoid biosynthesis in vivo and in peritoneal macrophages.
      We created mouse embryo fibroblast (MEF) cell lines that would facilitate
      investigation of the effect of mPGES-1 genetic deletion on prostanoid
      biosynthesis in fibroblast lineage cells and its subsequent effect on the
      expression of inducible NOS (iNOS) and nitrite biosynthesis using cells derived
      from mPGES-1 wild-type (WT), heterozygous (Het), and null mice. The results show
      that genetic deletion of mPGES-1 results in a dramatic decrease in PGE2
      production in Het and null MEFs under basal conditions and after stimulation with
      interleukin (IL)-1beta, suggesting that mPGES-1 is critically important for PGE2
      production. Furthermore, we show that mPGES-1 gene deletion results in diversion
      of prostanoid production from PGE2 to 6-keto PGF1alpha (the stable metabolic
      product of PGI2; prostacyclin) in a gene dose-dependent manner in Het and null
      MEFs compared with their WT counterparts, suggesting a shunting phenomenon within
      the arachidonic acid (AA) metabolic pathway. In addition, we show that mPGES-1
      gene deletion and subsequent decrease in PGE2 levels results in a differential
      induction profile of iNOS and nitrite levels (the stable breakdown product of
      nitric oxide (NO) in mPGES-1 WT MEFs compared with null MEFs. These results
      provide important information regarding the therapeutic potential for
      pharmacologic inhibition of mPGES-1 in inflammatory conditions.

PMID- 17023391
TI  - Ca2+ influx through CRAC channels activates cytosolic phospholipase A2,
      leukotriene C4 secretion, and expression of c-fos through ERK-dependent and 
      independent pathways in mast cells.
AB  - Cytosolic phospholipase A2 (cPLA2) is a Ca2+-dependent enzyme that mediates
      agonist-dependent arachidonic acid release in most cell types. Arachidonic acid
      can then be metabolized by the 5-lipoxygenase enzyme to generate the
      proinflammatory signal leukotriene C4 (LTC4). Here we report that Ca2+ entry
      through store-operated CRAC (Ca2+ release-activated Ca2+) channels activates the
      extracellular signal-regulated kinases (ERKs), members of the mitogen-activated
      protein kinase family, within minutes and this is necessary for stimulation of
      cPLA2. Ca2+ entry activates ERK indirectly, via recruitment of Ca2+-dependent
      protein kinase C alpha and betaI. Ca2+ influx also promotes translocation of
      cytosolic 5-lipoxygenase to the nuclear membrane, a key step in the activation of
      this enzyme. Translocation is dependent on ERK activation. A role for gene
      activation is shown by the finding that CRAC channel opening results in increased
      transcription and translation of c-fos. Inhibition of ERK activation failed to
      prevent c-fos expression. Our results show that CRAC channel activation elicits
      short-term effects through the co-coordinated regulation of two metabolic
      pathways (cPLA2 and 5-lipoxygenase), which results in the generation of both
      intra- and intercellular messengers within minutes, as well as longer term
      changes involving gene activation. These short-term effects are mediated via ERK,
      whereas, paradoxically, c-fos expression is not. Ca2+ influx through CRAC
      channels can therefore activate different signaling pathways at the same time,
      culminating in a range of temporally diverse responses.

PMID- 17023392
TI  - N-linked glycosylation of IL-13R alpha2 is essential for optimal IL-13 inhibitory
      activity.
AB  - A high-affinity receptor for interleukin (IL)-13 (interleukin-13R alpha 2) is
      over-expressed in disease-related fibroblasts and neoplastic cells and is
      involved in cancer, allergic, and inflammatory diseases. The extracellular domain
      of IL-13R alpha2 (ECD alpha2) could be cleaved, which serves as a decoy receptor.
      We have expressed and purified ECD alpha2 in both Escherichia coli (E. coli) and
      mammalian systems as a soluble fragment and studied its biological activities.
      Although both products of ECD alpha2 showed IL-13 inhibitory activities,
      mammalian cell-derived ECD alpha2 appeared to be superior compared with purified
      protein from E. coli. When expressed in E. coli, ECD alpha2 appeared to be a
      monomer of 42 but a 60 kDa protein when purified from mammalian cells due to
      heavy glycosylation. The purified glycosylated ECD alpha2 efficiently inhibited
      IL-13-induced STAT6 phosphorylation in immune and Hodgkin's lymphoma cell lines,
      IL-13 binding, and cytotoxicity of IL-13 cytotoxin in various cancer cell lines.
      The improved potency of mammalian cell-derived ECD alpha2 was shown over ECD
      alpha2/Fc fusion protein. The N-linked glycosylation of ECD alpha2 was found to
      be essential for optimal IL-13 inhibitory activity as deglycosylation by PNGase F
      showed lower activity. ECD alpha2 did not inhibit IL-4-induced STAT6
      phosphorylation, indicating that inhibitory effects of ECD alpha2 are receptor
      specific. These results indicate that glycosylated ECD alpha2 can serve as a
      potent inhibitor of IL-13 in a variety of conditions in which IL-13 is a key
      mediator, e.g., pulmonary, allergic, fibrotic, and neoplastic diseases.

PMID- 17023393
TI  - The human ClC-4 protein, a member of the CLC chloride channel/transporter family,
      is localized to the endoplasmic reticulum by its N-terminus.
AB  - Despite considerable similarity in their amino acid sequences and structural
      features, the mammalian members of the CLC chloride channel/transporter family
      have different subcellular locations. The subcellular location and function of
      one of these members, hClC-4, is controversial. To characterize its cellular
      function, we investigated its tissue distribution and subcellular location.
      Expression was high in excitable tissues such as the nervous system and skeletal
      muscle. When heterologously expressed in HEK293 cells and in skeletal muscle
      fibers, hClC-4 localizes to the endoplasmic/sarcoplasmic reticulum (ER/SR)
      membranes, in contrast to hClC-3, which localizes to vesicular structures. This
      location was confirmed by identification of endogenous ClC-4 in membrane
      fractions from mouse brain homogenate enriched for the sarco-endoplasmic
      reticulum ATPase SERCA2, an ER/SR marker. To identify the motif responsible for
      ER localization of hClC-4, we generated hClC-4 truncations and chimeras between
      hClC-4 and hClC-3 or the unrelated plasma membrane protein Ly49E. A stretch of
      amino acids, residues 14-63, at the N-terminus constitutes a novel motif both
      necessary and sufficient for targeting hClC-4 and other membrane proteins to the
      ER.

PMID- 17023395
TI  - Supporting information technology across health boards in New Zealand: themes
      emerging from the development of a shared services organization.
AB  - Shared services organizations are ascribed with adding value to business in
      several ways but especially by sharing resources and leading to economies of
      scale. However, these gains are not automatic and in some instances, particularly
      healthcare, they are difficult to achieve. This article describes a project to
      develop a shared services information technology infrastructure across two
      district health boards in New Zealand. The study reveals valuable insight into
      the crisis issues that accompany change management and identifies emergent themes
      that can be used to reduce negative impact.

PMID- 17023396
TI  - Personalizing web information for patients: linking patient medical data with the
      web via a patient personal knowledge base.
AB  - This paper describes ongoing study that examines problems with existing patient
      health information sources and investigates an approach for linking (i.e.
      integrating) data from a patient's medical record(s) with relevant health
      information on the web. The aim is to provide patients with simplified,
      customized and controlled access to web information. Data from patient medical
      records are extracted and linked with relevant health information on the web
      through a web search service. These are made available to patients through a web
      portal that we refer to as the patient knowledge base (PatientKB). Our
      integration approach utilizes term semantics (i.e. meaning) to enrich the web
      search and simplify medical terms for patients. In the current implementation,
      patients have guided, secure and relatively customized access to basic and
      relevant web information on their diagnoses. Future implementation will attempt
      to achieve further customization, extensibility and safety features. This paper
      investigates how ideas presented in an earlier study can be implemented.

PMID- 17023397
TI  - Working towards the informationist.
AB  - Current information is a critical component of good healthcare. In this article
      we offer a definition of a new health professional, the 'informationist', whose
      function it is to ensure evidence-based health practice. We describe the
      literature and discussions that led to the proposal of this new role, and offer a
      description of the steps being taken to further elaborate this career. In
      particular, we describe efforts at Johns Hopkins to train informationists and
      informaticists and to offer services that lead to the integration of these and
      other information professionals into clinical care, public health and research.

PMID- 17023398
TI  - An examination of the levels of confidence that consultants have in routinely
      collected clinical information.
AB  - Anecdotal evidence suggests that consultants have a low level of confidence in
      routinely collected clinical data. The aims of this study were to assess the
      actual levels of confidence in clinical information experienced by consultants
      and to understand the factors affecting confidence. A questionnaire was devised
      incorporating a scale to measure levels of confidence. This was disseminated to
      506 consultants and achieved a 57 per cent response rate. The confidence scale
      showed good internal reliability and the influential factors were modelled using
      multilinear regression. Consultant specialty, increased involvement in clinical
      coding, and participation in service planning/monitoring all had a significant
      effect. A small number of semi-structured interviews further examined these
      factors. Whilst the findings confirm there is scope to increase levels of
      confidence, the mean score indicated neither a high nor a low level of
      confidence. The results demonstrate that improving consultants' confidence in
      information is complex and requires a partnership approach.

PMID- 17023399
TI  - Using geographical information systems and spatial microsimulation for the
      analysis of health inequalities.
AB  - The paper presents a spatial microsimulation approach to the analysis of health
      inequalities. A dynamic spatial microsimulation model of Britain, under
      development at the Universities of Leeds and Sheffield, uses data from the
      censuses of 1971, 1981 and 1991 and the British Household Panel Survey to
      simulate urban and regional populations in Britain. Geographical information
      systems and spatial microsimulation are used for the analysis of health
      inequalities in British regions in a 30 year simulation. The interdependencies
      between socio-economic characteristics and health variables such as limiting long
      term illness are discussed. One of the innovative features of the model is the
      estimation of variables such as household income at the small area level, which
      can then be used to classify individuals. The health situation of different
      simulated individuals in different areas is investigated and the role of socio
      economic characteristics in determining health is evaluated.

PMID- 17023400
TI  - Quality labelling of medical web content.
AB  - As the number of medical websites in various languages increases, it is
      increasingly necessary to establish specific criteria and control measures that
      give consumers some guarantee that the health websites they are visiting meet a
      minimum level of quality standards. Further, reassurance is needed that the
      professionals offering the information are suitably qualified. The paper briefly
      presents the current mechanisms for labelling medical web content and introduces
      the work done in the EC-funded project Quatro. This has defined a vocabulary for
      quality labels and a schema to deliver them in a machine-processable format. In
      addition, the paper proposes the development of a labelling platform that will
      assist the work of medical labelling agencies in automating, up to a certain
      level, the retrieval of unlabelled medical websites and their labelling, and the
      monitoring of labelled websites as to whether they are still satisfying the
      criteria.

PMID- 17023401
TI  - Extending the role of a healthcare digital library environment to support
      orthopaedic research.
AB  - A digital archive, together with its users and its contents, does not exist in
      isolation; there is a cycle of activities which provides the context for the
      archive's existence. In arguing for the broadening of the traditional view of
      digital libraries as merely collections towards the processes of collecting and
      deploying, we have developed an extend ed digital library environment for
      orthopaedic surgeons which bridges the gap between the undertaking of
      experimental work and the dissemination of its results through electronic
      publication.

PMID- 17023402
TI  - Next-generation applications in healthcare digital libraries using semantic
      service composition and coordination.
AB  - Healthcare digital libraries (DLs) increasingly make use of dedicated services to
      access functionality and/or data. Semantic (web) services enhance single services
      and facilitate compound services, thereby supporting advanced applications on top
      of a DL. The traditional process management approach tends to focus on process
      definition at build time rather than on actual service events in run time, and to
      anticipate failures in order to define appropriate strategies. This paper
      presents a novel approach where service coordination is distributed among a set
      of agents. A dedicated component plans compound semantic services on demand for a
      particular application. In failure, the planner is reinvoked to define contin-
      gency strategies. Finally, matchmaking is effected at runtime by choosing the
      appropriate service provider. These combined technologies will provide key
      support for highly flexible next-generation DL applications. Such technologies
      are under development within CASCOM.

PMID- 17023403
TI  - HDLalert - a healthcare DL alerting system: from user needs to implementation.
AB  - In the health domain, there are many circumstances where clinicians (i.e.
      doctors, nurses, allied health professionals) and patients wish to track changes
      in medical knowledge. However, existing 'news' or 'alert' services provide
      relatively limited means for selecting which information to receive. The result
      is that clinicians and patients often receive information that is inappropriate,
      irrelevant or simply too much. In this paper, we detail alert-relevant findings
      from several international user studies (e.g. UK, Germany and New Zealand)
      incorporating both clinical staff (across several hospitals) and patients'
      perceptions. These findings demonstrate the importance of context, in terms of
      both the user's task and immediate environment. We introduce a novel alerting
      architecture that can provide a finely tailored stream of alerts to the user, and
      provides further support to assist the interpretation of received material.

PMID- 17023404
TI  - Lessons learned from evaluation of the use of the National electronic Library of
      Infection.
AB  - The National electronic Library of Infection (NeLI: http://www.neli.org.uk) in
      the UK is a freely available portal to key evidence and guidelines in the
      infectious disease field. This paper discusses 5 years of evaluation of the pilot
      library and how this evaluation informed design of the new library website. The
      importance of combining qualitative and quantitative evaluation is highlighted
      and the results of web access logs analysis, free text search query analysis and
      an online user survey are compared. The paper concludes with a discussion of
      lessons learned for future development and evaluation of this Internet digital
      library.

PMID- 17023405
TI  - Healthcare information giving services: technologies and everyday practicalities.
AB  - This paper presents findings from observational studies of work practice in two
      'information giving' services - a poisons information service and a mental health
      helpline - as a precursor to informing the design of such services. Our work high
      lights the interactions that constitute the requesting and giving of information
      and the role of intermediaries in the delivery of recipient-designed information.
      We propose a shift of focus from the logic of information in system design to one
      that encompasses the practicalities of information giving.

PMID- 17023406
TI  - Patient information needs: pre- and post-consultation.
AB  - This paper presents findings from a study of information seeking behaviour by
      National Health Service patients which explored motivational triggers for infor-
      mation needs. Previous research has highlighted the importance of contextual
      elements in users' changing information needs. This paper highlights how those
      needs may centre on specific events: in particular, a patient's consultation with
      their doctor. Patients initiate information seeking to assess whether they need
      clinical intervention, in preparation for the patient-doctor consultation and to
      verify the diagnosis or treatment stemming from that consultation. The study has
      revealed that having confidence in health practitioners is one key motiva- tion
      for information seeking. Another is a desire to use health service resources
      judiciously, efficiently and effectively.

PMID- 17023407
TI  - Impact of workflow-integrated corollary orders on aminoglycoside monitoring in
      children.
AB  - Computerized provider order entry (CPOE) and clinical decision support improve
      medication prescribing safety in adults. However, effective therapy for children
      requires dosing based on circulating medication levels. We examined the
      introduction of a computerized corollary order for aminoglycoside blood level
      monitoring. The study was divided into baseline (BP) and corollary order (CP)
      periods. In the CP, we implemented a workflow-integrated reminder to order blood
      levels and presented this to the clinician during each aminoglycoside ordering
      session. Appropriate laboratory monitoring was 128/159 (80.5%) courses in the BP
      and 146/177 (82.5%) courses in the CP. Thus introduction of the order did not
      significantly improve laboratory monitoring rates, nor did it result in a
      reduction in the rate of either toxic or subtherapeutic levels. However,
      aminoglycoside corollary orders may have an important role in institutions where
      pharmacists are not actively involved in monitoring therapy.

PMID- 17023408
TI  - Clinical, information and business process modeling to promote development of
      safe and flexible software.
AB  - Using a factorial vignette survey and modeling methodology, we developed clinical
      and information models - incorporating evidence base, key concepts, relevant
      terms, decision-making and workflow needed to practice safely and effectively -
      to guide the development of an integrated rule-based knowledge module to support
      prescribing decisions in asthma. We identified workflows, decision-making
      factors, factor use, and clinician information requirements. The Unified Modeling
      Language (UML) and public domain software and knowledge engineering tools (e.g.
      Protege) were used, with the Australian GP Data Model as the starting point for
      expressing information needs. A Web Services service-oriented architecture
      approach was adopted within which to express functional needs, and clinical
      processes and workflows were expressed in the Business Process Execution Language
      (BPEL). This formal analysis and modeling methodology to define and capture the
      process and logic of prescribing best practice in a reference implementation is
      fundamental to tackling deficiencies in prescribing decision support software.

PMID- 17023409
TI  - Using neural networks and just nine patient-reportable factors of screen for AMI.
AB  - The study investigated the effect of different input selections on the
      performance of artificial neural networks in screening for acute myocardial
      infarction (AMI) in Malaysian patients complaining of chest pain. We used
      hospital data to create neural networks with four input selections and used these
      to diagnose AMI. A 10-fold cross-validation and committee approach was used. All
      the neural networks using various input selections outperformed a multiple
      logistic regression model, although the difference was not statistically
      significant. The neural networks achieved an area under the ROC curve of 0.792
      using nine inputs, whereas multiple logistic regression achieved 0.739 using 64
      inputs. Sensitivity levels of over 90 per cent were achieved using low output
      threshold levels. Specificity levels of over 90 per cent were achieved using
      threshold levels of 0.4-0.5. Thus neural networks can perform as well as multiple
      logistic regression models even when using far fewer inputs.

PMID- 17023410
TI  - Population access to hospital emergency departments and the impacts of health
      reform in New Zealand.
AB  - In the current political climate of evidence-based research, GIS has emerged as a
      powerful research tool as it allows spatial and social health inequality to be
      explored efficiently. This article explores the impact health reforms had on
      geographical accessibility to hospital emergency department (ED) services in New
      Zealand from 1991 to 2001. Travel time was calculated using least-cost path
      analysis, which identified the shortest travel time from each census enumeration
      district through a road network to the nearest ED. This research found that the
      population further than 60 minutes from an ED has increased with some areas being
      affected more than others. Some of this increase is attributed to increases in
      population rather than the closing of hospitals. The findings will be discussed
      within the context of the health policy reform era and changes to health service
      provision.

PMID- 17023411
TI  - When computers should remain computers: a qualitative look at the humanization of
      health care technology.
AB  - This article describes users' responses to human-like characteristics of two
      health promotion IVR systems. We conducted a qualitative evaluation of two
      systems that promoted physical activity and healthy dietary behavior
      respectively. Two themes that emerged dealt with favorable responses of the users
      to the machine's intrinsic qualities of being insentient and non-judgmental, and
      the users' precarious sensitivity to certain human-like characteristics of the
      systems, namely, the content of the scripts and the recorded human voice. The
      article suggests that design factors that are intended to enhance human-like
      characteristics of these applications elicit both positive and negative
      responses. Thus, even though many users enjoyed and appreciated the human-like
      performance of the machine, some who were more sensitive about their exercise or
      dietary behavior preferred a non-affective response by these systems, i.e. they
      preferred the system to behave like a 'machine' (without emotions) rather than a
      'person'.

PMID- 17023412
TI  - Loss of nidogen-1 and -2 results in syndactyly and changes in limb development.
AB  - Nidogens are two ubiquitous basement membrane proteins produced mainly by
      mesenchymal cells. Nidogen-mediated interactions, in particular with laminin,
      collagen IV, and perlecan have been considered important in the formation and
      maintenance of the basement membrane. However, whereas mice lacking both nidogen
      isoforms or carrying mutations in the high affinity nidogen-binding site upon the
      laminin gamma1 chain have specific basement membrane defects in certain organs,
      particularly in the lung, characterization of these mice has also shown that
      basement membrane formation per se does not need nidogens or the laminin-nidogen
      interaction. Limb development requires the complex interplay of numerous growth
      factors whose expression is dependent upon the apical ectodermal ridge. Here, we
      show that lack of nidogen-1 and -2 results in a specific and time-limited failure
      in the ectodermal basement membrane of the limb bud. The absence of this basement
      membrane leads to aberrant apical ectodermal ridge formation. It also causes
      altered distribution of growth factors, such as fibroblast growth factors and
      leads to a fully penetrant soft tissue syndactyly caused by the dysregulation of
      interdigital apoptosis. Further, in certain animals more severe changes in bone
      formation occur, providing evidence for the interplay between growth factors and
      the extracellular matrix.

PMID- 17023413
TI  - Random mutagenesis of the complement factor 5a (C5a) receptor N terminus provides
      a structural constraint for C5a docking.
AB  - The N terminus of G protein-coupled receptors has been implicated in binding to
      peptide hormones. We have used random saturation mutagenesis to identify
      essential residues in the N terminus of the human complement factor 5a receptor
      (C5aR). In a library of N-terminal mutant C5aR molecules screened for activation
      by C5a, residues 24-30 of the C5aR showed a marked propensity to mutate to
      cysteine, most likely indicating that sulfhydryl groups at these positions are
      appropriately situated to form disulfide interactions with the unpaired Cys(27)
      of human C5a. This presumptive spatial constraint allowed the ligand to be
      computationally docked to the receptor to form a model of the C5a/C5aR
      interaction. When the N-terminal mutant C5aR library was rescreened with C5a
      C27R, a ligand incapable of disulfide interactions, no individual position in the
      N terminus was essential for receptor signaling. However, the region 19-29 was
      relatively highly conserved in the functional mutants, further demonstrating that
      this region of the C5aR makes a productive physiologic interaction with the C5a
      ligand.

PMID- 17023414
TI  - Structure of the Escherichia coli O157:H7 heme oxygenase ChuS in complex with
      heme and enzymatic inactivation by mutation of the heme coordinating residue His
      193.
AB  - Heme oxygenases catalyze the oxidation of heme to biliverdin, CO, and free iron.
      For pathogenic microorganisms, heme uptake and degradation are critical
      mechanisms for iron acquisition that enable multiplication and survival within
      hosts they invade. Here we report the first crystal structure of the pathogenic
      Escherichia coli O157:H7 heme oxygenase ChuS in complex with heme at 1.45 A
      resolution. When compared with other heme oxygenases, ChuS has a unique fold,
      including structural repeats and a beta-sheet core. Not surprisingly, the mode of
      heme coordination by ChuS is also distinct, whereby heme is largely stabilized by
      residues from the C-terminal domain, assisted by a distant arginine from the N
      terminal domain. Upon heme binding, there is no large conformational change
      beyond the fine tuning of a key histidine (His-193) residue. Most intriguingly,
      in contrast to other heme oxygenases, the propionic side chains of heme are
      orientated toward the protein core, exposing the alpha-meso carbon position where
      O(2) is added during heme degradation. This unique orientation may facilitate
      presentation to an electron donor, explaining the significantly reduced
      concentration of ascorbic acid needed for the reaction. Based on the ChuS-heme
      structure, we converted the histidine residue responsible for axial coordination
      of the heme group to an asparagine residue (H193N), as well as converting a
      second histidine to an alanine residue (H73A) for comparison purposes. We
      employed spectral analysis and CO measurement by gas chromatography to analyze
      catalysis by ChuS, H193N, and H73A, demonstrating that His-193 is the key residue
      for the heme-degrading activity of ChuS.

PMID- 17023415
TI  - Gemin8 is required for the architecture and function of the survival motor neuron
      complex.
AB  - The biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) in
      higher eukaryotes requires the functions of several cellular proteins and
      includes nuclear as well as cytoplasmic phases. In the cytoplasm, a
      macromolecular complex containing the survival motor neuron (SMN) protein, Gemin2
      8 and Unrip mediates the ATP-dependent assembly of Sm proteins and snRNAs into
      snRNPs. To carry out snRNP assembly, the SMN complex binds directly to both Sm
      proteins and snRNAs; however, the contribution of the individual components of
      the SMN complex to its composition, interactions, and function is poorly
      characterized. Here, we have investigated the functional role of Gemin8 using
      novel monoclonal antibodies against components of the SMN complex and RNA
      interference experiments. We show that Gemin6, Gemin7, and Unrip form a stable
      cytoplasmic complex whose association with SMN requires Gemin8. Gemin8 binds
      directly to SMN and mediates its interaction with the Gemin6/Gemin7 heterodimer.
      Importantly, loss of Gemin6, Gemin7, and Unrip interaction with SMN as a result
      of Gemin8 knockdown affects snRNP assembly by impairing the SMN complex
      association with Sm proteins but not with snRNAs. These results reveal the
      essential role of Gemin8 for the proper structural organization of the SMN
      complex and the involvement of the heteromeric subunit containing Gemin6, Gemin7,
      Gemin8, and Unrip in the recruitment of Sm proteins to the snRNP assembly
      pathway.

PMID- 17023416
TI  - Structural determinants in the group III truncated hemoglobin from Campylobacter
      jejuni.
AB  - Truncated hemoglobins (trHbs) constitute a distinct lineage in the globin
      superfamily, distantly related in size and fold to myoglobin and monomeric
      hemoglobins. Their phylogenetic analyses revealed that three groups (I, II, and
      III) compose the trHb family. Group I and II trHbs adopt a simplified globin
      fold, essentially composed of a 2-on-2 alpha-helical sandwich, wrapped around the
      heme group. So far no structural data have been reported for group III trHbs.
      Here we report the three-dimensional structure of the group III trHbP from the
      eubacterium Campylobacter jejuni. The 2.15-A resolution crystal structure of C.
      jejuni trHbP (cyano-met form) shows that the 2-on-2 trHb fold is substantially
      conserved in the trHb group III, despite the absence of the Gly-based sequence
      motifs that were considered necessary for the attainment of the trHb specific
      fold. The heme crevice presents important structural modifications in the C-E
      region and in the FG helical hinge, with novel surface clefts at the proximal
      heme site. Contrary to what has been observed for group I and II trHbs, no
      protein matrix tunnel/cavity system is evident in C. jejuni trHbP. A gating
      movement of His(E7) side chain (found in two alternate conformations in the
      crystal structure) may be instrumental for ligand entry to the heme distal site.
      Sequence conservation allows extrapolating part of the structural results here
      reported to the whole trHb group III.

PMID- 17023417
TI  - A membrane-proximal tetracysteine motif contributes to assembly of
      CD3deltaepsilon and CD3gammaepsilon dimers with the T cell receptor.
AB  - Assembly of the T cell receptor (TCR) with its dimeric signaling modules,
      CD3deltaepsilon, CD3gammaepsilon, and zetazeta, is organized by transmembrane
      (TM) interactions. Each of the three assembly steps requires formation of a three
      helix interface involving one particular basic TCR TM residue and two acidic TM
      residues of the respective signaling dimer. The extracellular domains of
      CD3deltaepsilon and CD3gammaepsilon contribute to assembly, but TCR interaction
      sites on CD3 dimers have not been defined. The structures of the extracellular
      domains of CD3deltaepsilon and CD3gammaepsilon demonstrated parallel beta-strands
      ending at the first cysteine in the CXXCXEXXX motif present in the stalk segment
      of each CD3 chain. Mutation of the membrane-proximal cysteines impaired assembly
      of either CD3 dimer with TCR, and little complex was isolated when all four
      membrane-proximal cysteines were mutated to alanine. These mutations had,
      however, no discernable effect on CD3deltaepsilon or CD3gammaepsilon
      dimerization. CD3deltaepsilon assembled with a TCRalpha mutant that lacked both
      immunoglobulin domains, but shortening of the TCRalpha connecting peptide reduced
      assembly, consistent with membrane-proximal TCRalpha-CD3deltaepsilon
      interactions. Chelation of divalent cations did not affect assembly, indicating
      that coordination of a cation by the tetracysteine motif was not required. The
      membrane-proximal cysteines were within close proximity but only formed covalent
      CD3 dimers when one cysteine was mutated. The four cysteines may thus form two
      intrachain disulfide bonds integral to the secondary structure of CD3 stalk
      regions. The three-chain interaction theme first established for the TM domains
      thus extends into the membrane-proximal domains of TCRalpha-CD3deltaepsilon and
      TCRbeta-CD3gammaepsilon.

PMID- 17023418
TI  - Unique and overlapping transcriptional roles of arylhydrocarbon receptor nuclear
      translocator (Arnt) and Arnt2 in xenobiotic and hypoxic responses.
AB  - Arnt and the homologous Arnt2 share a high degree of sequence similarity and are
      believed to function as obligate common partners for a number of basic helix-loop
      helix (bHLH)-PAS transcription factors including arylhydrocarbon receptor (AhR)
      and HIFalpha. Genetic disruption of both Arnt and Arnt2 demonstrated both unique
      and overlapping functions in response to environmental stimuli and during mouse
      development. Either stably or transiently expressed Arnt/Arnt2 wild type and
      various mutants or chimeric constructs in Hepa1-c4 cells exhibit similar levels
      of hypoxic response element-driven reporter gene expression and the induction of
      endogenous Glut-1 through binding with HIFalpha in response to hypoxia. In
      contrast, we observed clear functional differences in the ability of Arnt and
      Arnt2 to induce xenobiotic response element-driven reporter and endogenous CYP1A1
      gene expression. In contrast with Arnt, Arnt2 was practically incapable of
      interacting with ligand-activated AhR to induce the expression of target genes
      for xenobiotic-metabolizing enzymes in response to xenobiotics. The differential
      binding of AhR by Arnt and Arnt2 can be ascribed to a single His/Pro amino acid
      difference in the PASB region of Arnt and Arnt2, suggesting that the PASB/PASB
      interaction between bHLH-PAS transcription factors plays a selective role for
      their specific partner molecule.

PMID- 17023419
TI  - A small molecule agonist of an integrin, alphaLbeta2.
AB  - The binding of integrin alpha(L)beta(2) to its ligand intercellular adhesion
      molecule-1 is required for immune responses and leukocyte trafficking. Small
      molecule antagonists of alpha(L)beta(2) are under intense investigation as
      potential anti-inflammatory drugs. We describe for the first time a small
      molecule integrin agonist. A previously described alpha/beta I allosteric
      inhibitor, compound 4, functions as an agonist of alpha(L)beta(2) in Ca(2+) and
      Mg(2+)and as an antagonist in Mn(2+). We have characterized the mechanism of
      activation and its competitive and noncompetitive inhibition by different
      compounds. Although it stimulates ligand binding, compound 4 nonetheless inhibits
      lymphocyte transendothelial migration. Agonism by compound 4 results in
      accumulation of alpha(L)beta(2) in the uropod, extreme uropod elongation, and
      defective de-adhesion. Small molecule integrin agonists open up novel therapeutic
      possibilities.

PMID- 17023420
TI  - Regulation of AMP-activated protein kinase by multisite phosphorylation in
      response to agents that elevate cellular cAMP.
AB  - The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key
      regulators of cellular metabolism. In this study, we show that AMPK activity is
      attenuated in response to cAMP-elevating agents through modulation of at least
      two of its alpha subunit phosphorylation sites, viz. alpha-Thr(172) and alpha1
      Ser(485)/alpha2-Ser(491), in the clonal beta-cell line INS-1 as well as in mouse
      embryonic fibroblasts and COS cells. Forskolin, isobutylmethylxanthine, and the
      glucose-dependent insulinotropic peptide inhibited AMPK activity and reduced
      phosphorylation of the activation loop alpha-Thr(172) via inhibition of
      calcium/calmodulin-dependent protein kinase kinase-alpha and -beta, but not LKB1.
      These agents also enhanced phosphorylation of alpha-Ser(485/491) by the cAMP
      dependent protein kinase. AMPK alpha-Ser(485/491) phosphorylation was necessary
      but not sufficient for inhibition of AMPK activity in response to
      forskolin/isobutylmethylxanthine. We show that AMPK alpha-Ser(485/491) can be a
      site for autophosphorylation, which may play a role in limiting AMPK activation
      in response to energy depletion or other regulators. Thus, our findings not only
      demonstrate cross-talk between the cAMP/cAMP-dependent protein kinase and AMPK
      signaling modules, but also describe a novel mechanism by which multisite
      phosphorylation of AMPK contributes to regulation of its enzyme activity.

PMID- 17023421
TI  - Deletion of the gene encoding the ubiquitously expressed glucose-6-phosphatase
      catalytic subunit-related protein (UGRP)/glucose-6-phosphatase catalytic subunit
      beta results in lowered plasma cholesterol and elevated glucagon.
AB  - In liver, glucose-6-phosphatase catalyzes the hydrolysis of glucose-6-phosphate
      (G6P) to glucose and inorganic phosphate, the final step in the gluconeogenic and
      glycogenolytic pathways. Mutations in the glucose-6-phosphatase catalytic subunit
      (G6Pase) give rise to glycogen storage disease (GSD) type 1a, which is
      characterized in part by hypoglycemia, growth retardation, hypertriglyceridemia,
      hypercholesterolemia, and hepatic glycogen accumulation. Recently, a novel G6Pase
      isoform was identified, designated UGRP/G6Pase-beta. The activity of UGRP
      relative to G6Pase in vitro is disputed, raising the question as to whether G6P
      is a physiologically important substrate for this protein. To address this issue
      we have characterized the phenotype of UGRP knock-out mice. G6P hydrolytic
      activity was decreased by approximately 50% in homogenates of UGRP(-/-) mouse
      brain relative to wild type tissue, consistent with the ability of UGRP to
      hydrolyze G6P. In addition, female, but not male, UGRP(-/-) mice exhibit growth
      retardation as do G6Pase(-/-) mice and patients with GSD type 1a. However, in
      contrast to G6Pase(-/-) mice and patients with GSD type 1a, UGRP(-/-) mice
      exhibit no change in hepatic glycogen content, blood glucose, or triglyceride
      levels. Although UGRP(-/-) mice are not hypoglycemic, female UGRP(-/-) mice have
      elevated ( approximately 60%) plasma glucagon and reduced ( approximately 20%)
      plasma cholesterol. We hypothesize that the hyperglucagonemia prevents
      hypoglycemia and that the hypocholesterolemia is secondary to the
      hyperglucagonemia. As such, the phenotype of UGRP(-/-) mice is mild, indicating
      that G6Pase is the major glucose-6-phosphatase of physiological importance for
      glucose homeostasis in vivo.

PMID- 17023422
TI  - Structure/function relationships of CCR8 agonists and antagonists. Amino-terminal
      extension of CCL1 by a single amino acid generates a partial agonist.
AB  - We describe here the interactions of CCR8 with its ligands using both CCR8
      transfectants and a T-cell line expressing the receptor endogenously. Of the CCR8
      agonists reported previously, only CCL1 and vMIP-I exhibited potency in assays of
      intracellular calcium flux, chemotaxis, and receptor internalization, this latter
      mechanism being dependent upon the expression of beta-arrestins 1 and 2 but
      independent of Galpha(i) signaling. NH(2)-terminal extension of the mature CCL1
      sequence by a serine residue (Ser-CCL1) resulted in a partial agonist with a
      reduced affinity for CCR8, suggesting that the NH(2) terminus of the ligand plays
      a role in ligand binding to an intrahelical site. Attempts to identify key
      residues within this site revealed that the conserved glutamic acid residue in
      transmembrane helix 7, Glu-286, is crucial for trafficking of the receptor to the
      cell surface, while Asp-97 of transmembrane helix 2 is dispensable. CCL7 was
      found to inhibit both Ser-CCL1 and vMIP-I responses but not those of CCL1 itself.
      Similarly, vMIP-I responses were more than 2 orders of magnitude more sensitive
      to the specific CCR8 antagonist MC148 than those induced by CCL1, which is
      difficult to reconcile with the reported affinities for the receptor.
      Collectively, these data suggest that the CCR8 ligands are allotropic, binding to
      distinct sites within CCR8 and that the human immune system may have evolved to
      use CCL7 as a selective antagonist of viral chemokine activity at CCR8 but not
      those of the host ligand.

PMID- 17023423
TI  - Side chain-dependent stacking modulates tau filament structure.
AB  - The misfolding of proteins into highly ordered fibrils with similar physical
      properties is a hallmark of many degenerative diseases. Here, we use the
      microtubule associated protein tau as a model system to investigate the role of
      amino acid side chains in the formation of such fibrils. We identify a region
      (positions 272-289) in the tau protein that, in the fibrillar state, either forms
      part of a core of parallel, in-register, beta-strands, or remains unfolded.
      Single point mutations are sufficient to control this conformational switch with
      disease mutants G272V and DeltaK280 (found in familial forms of dementia)
      inducing a folded state. Through systematic mutagenesis we derive a propensity
      scale for individual amino acids to form fibrils with parallel, in-register, beta
      strands. This scale should not only apply to tau fibrils but generally to all
      fibrils with same strand arrangement.

PMID- 17023424
TI  - Modulation of Rad26- and Rpb9-mediated DNA repair by different promoter elements.
AB  - Rad26, the yeast homologue of human Cockayne syndrome group B protein, and Rpb9,
      a nonessential subunit of RNA polymerase II, have been shown to mediate two
      subpathways of transcription-coupled DNA repair in yeast. Here we show that Rad26
      and Rpb9-mediated repair in the yeast GAL1 gene is differently modulated by
      different promoter elements. The initiation site and efficiency of Rad26-mediated
      repair in the transcribed strand are determined by the upstream activating
      sequence (UAS) but not by the TATA or local sequences. The role of UAS in
      determining the Rad26-mediated repair is not through loading of RNA polymerase II
      or the transcriptional regulatory complex SAGA. However, both the UAS and the
      TATA sequences are essential for confining Rad26-mediated repair to the
      transcribed strand. Mutation of the TATA sequence, which greatly reduces
      transcription, or deletion of the TATA or mutation of the UAS, which completely
      abolishes transcription, causes Rad26-mediated repair to occur in both strands.
      Rpb9-mediated repair only occurs in the transcribed strand and is efficient only
      in the presence of both TATA and UAS sequences. Also, the efficiency of Rpb9
      mediated repair is dependent on the SAGA complex. Our results suggest that Rad26
      mediated repair can be either transcription-coupled, provided that a substantial
      level of transcription is present, or transcription-independent, if the
      transcription is too low or absent. In contrast, Rpb9-mediated repair is strictly
      transcription-coupled and is efficient only when the transcription level is high.

PMID- 17023425
TI  - Differential transcriptional control of the superoxide dismutase-2 kappaB element
      in neurons and astrocytes.
AB  - In addition to their conventional G-C/T target sequences, Sp1 family
      transcription factors (Sp-factors) can interact with a subset of the target
      sequences for NFkappaB. Due to the low level of bona fide NFkappaB activity in
      most resting cells, this interaction between Sp-factors and kappaB-sites could
      play important roles in cell function. Here we used mutagenesis of a canonical
      kappaB element from the immunoglobulin and HIV promoters to identify the GC-rich
      sequences at each end required for Sp-factor targeting. Through screening of
      multiple kappaB elements, a sequence element located in the second intron of
      superoxide dismutase-2 (SOD2) was identified as a good candidate for both
      NFkappaB and Sp-factor binding. In neurons, the prominent proteins interacting
      with this site were Sp3 and Sp4, whereas Sp1, Sp3, and NFkappaB were associated
      with this site in astroglia. The neuronal Sp-factors repressed transcriptional
      activity through this kappaB-site. In contrast, astroglial Sp-factors activated
      promoter activity through the same element. NFkappaB contributed to control of
      the SOD2 kappaB element only in astrocytes. These findings imply that cell-type
      specificity of transcription in the central nervous system, particularly with
      regard to kappaB elements, may include two unique aspects of neurons: 1) a
      recalcitrant NFkappaB and 2) the substitution of Sp4 for Sp1.

PMID- 17023426
TI  - Cyclooxygenase-2-derived prostaglandin E(2) directs oocyte maturation by
      differentially influencing multiple signaling pathways.
AB  - The process of oocyte maturation, which impacts ovulation and fertilization, is
      complex and requires an integration of the endocrine, paracrine, juxtacrine, and
      autocrine signaling pathways. This process involves an intimate interaction
      between the oocyte and encircling cumulus cells within a follicle, a unique venue
      for somatic and germ cell communication. Cumulus cell expansion and resumption of
      meiosis with germinal vesicle breakdown are major events in oocyte maturation.
      Cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2)) is a known critical
      mediator of oocyte maturation, but the diverse function of this lipid mediator in
      oocyte maturation, ovulation, and fertilization has not been fully appreciated.
      We show here that gonadotropins in coordination with PGE(2) signaling via its
      cell surface G-protein-coupled EP2 and EP4 receptor subtypes direct cumulus cell
      expansion and survival and oocyte meiotic maturation by differentially impacting
      cAMP-dependent protein kinase, MAPK, NF-kappaB, and phosphatidylinositol 3
      kinase/Akt pathways. This study is unique in the sense that it provides evidence
      for new site- and event-specific involvement of these signaling pathways under
      the influence of COX-2-derived PGE(2) during the critical stages of this somatic
      germ cell interaction, an absolute requirement for oocyte maturation.

PMID- 17023427
TI  - Cloning and initial characterization of a new subunit for mammalian serine
      palmitoyltransferase.
AB  - Serine-palmitoyltransferase (SPT) catalyzes the rate-limiting step of the de novo
      synthesis of sphingolipids. SPT is considered to be a heterodimer composed of two
      subunits, SPTLC1 and SPTLC2. Here we report the identification of a novel, third,
      SPT subunit (SPTLC3) that shows 68% homology to the SPTLC2 subunit. Quantitative
      real-time PCR revealed that SPTLC3 expression is highly variable between
      different human tissues and cell lines. The highest expression was observed in
      placenta tissue and human trophoblast cell lines. The overexpression of SPTLC3 in
      Hek293 cells, which otherwise have very little endogenous SPTLC3, led to a 2- to
      3-fold increase in cellular SPT activity. Silencing of SPTLC3 expression in HepG2
      cells or human trophoblast cells by transfecting SPTLC3-specific siRNA resulted
      in a significant reduction of cellular SPT activity. The expression of two SPT
      isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific
      requirements of sphingolipid synthesis.

PMID- 17023428
TI  - The transcriptional response of the yeast Na(+)-ATPase ENA1 gene to alkaline
      stress involves three main signaling pathways.
AB  - Adaptive response of the yeast Saccharomyces cerevisiae to environmental
      alkalinization results in remodeling of gene expression. A key target is the gene
      ENA1, encoding a Na(+)-ATPase, whose induction by alkaline pH has been shown to
      involve calcineurin and the Rim101/Nrg1 pathway. Previous functional analysis of
      the ENA1 promoter revealed a calcineurin-independent pH responsive region (ARR2,
      83 nucleotides). We restrict here this response to a small (42 nucleotides) ARR2
      5.-region, named MCIR (minimum calcineurin independent response), which contains
      a MIG element, able to bind Mig1,2 repressors. High pH-induced response driven
      from this region was largely abolished in snf1 cells and moderately reduced in a
      rim101 strain. Cells lacking Mig1 or Mig2 repressors had a near wild type
      response, but the double mutant presented a high level of expression upon
      alkaline stress. Deletion of NRG1 (but not of NRG2) resulted in increased
      expression. Induction from the MCIR region was marginal in a quadruple mutant
      lacking Nrg1,2 and Mig1,2 repressors. In vitro band shift experiments
      demonstrated binding of Nrg1 to the 5. end of the ARR2 region. Furthermore, we
      show that Nrg1 binds in vivo around the MCIR region under standard growth
      conditions, and that binding is largely abolished after high pH stress.
      Therefore, the calcineurin-independent response of the ENA1 gene is under the
      regulation of Rim101 (through Nrg1) and Snf1 (through Nrg1 and Mig2).
      Accordingly, induction by alkaline stress of the entire ENA1 promoter in a snf1
      rim101 mutant in the presence of the calcineurin inhibitor FK506 is completely
      abolished. Thus, the transcriptional response to alkaline stress of the ENA1 gene
      integrates three different signaling pathways.

PMID- 17023429
TI  - BRG1 chromatin remodeling activity is required for efficient chromatin binding by
      repressor element 1-silencing transcription factor (REST) and facilitates REST
      mediated repression.
AB  - Chromatin remodeling enzymes such as SWI/SNF use the hydrolysis of ATP to power
      the movement of nucleosomes with respect to DNA. BRG1, one of the ATPases of the
      SWI/SNF complex, can be recruited by both activators and repressors, although the
      precise role of BRG1 in mechanisms of repression has thus far remained unclear.
      One transcription factor that recruits BRG1 as a corepressor is the repressor
      element 1-silencing transcription factor (REST). Here we address for the first
      time the mechanism of BRG1 activity in gene repression. We found that BRG1
      enhanced REST-mediated repression at some REST target genes by increasing the
      interaction of REST with the local chromatin at its binding sites. Furthermore,
      REST-chromatin interactions, mediated by BRG1, were enhanced following an
      increase in histone acetylation in a manner dependent on the BRG1 bromodomain.
      Our data suggest that BRG1 facilitates REST repression by increasing the
      interaction between REST and chromatin. Such a mechanism may be applicable to
      other transcriptional repressors that utilize BRG1.

PMID- 17023430
TI  - Lysophospholipids control integrin-dependent adhesion in splenic B cells through
      G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11).
AB  - Integrin-mediated adhesion is a crucial step in lymphocyte extravasation and
      homing. We show here that not only the chemokines CXCL12 and CXCL13 but also the
      lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA)
      enhance adhesion of murine follicular and marginal zone B cells to ICAM-1 in
      vitro. This process involves clustering of integrin LFA-1 and is blocked by
      pertussis toxin, suggesting that G(i) family G-proteins are involved. In
      addition, lysophospholipid-induced adhesion on ICAM-1 depends on Rho and
      Rhokinase, indicative of an involvement of G(12)/G(13), possibly also G(q)/G(11)
      family G-proteins. We used G(12)/G(13)- or G(q)/G(11)-deficient B cells to study
      the role of these G-protein families in lysophospholipid-induced adhesion and
      found that the pro-adhesive effects of LPA and S1P are completely abrogated in
      G(12)/G(13)-deficient marginal zone B cells, reduced in G(12)/G(13)-deficient
      follicular B cells, and normal in G(q)/G(11)-deficient B cells. We also show that
      loss of lysophospholipid-induced adhesion results in disinhibition of migration
      in response to the follicular chemokine CXCL13, which might contribute to the
      abnormal localization of splenic B cell populations observed in B cell-specific
      G(12)/G(13)-deficient mice in vivo. Taken together, this study shows that
      lysophospholipids regulate integrin-mediated adhesion of splenic B cells to ICAM
      1 through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11).

PMID- 17023431
TI  - Antisense targeting of CXXC finger protein 1 inhibits genomic cytosine
      methylation and primitive hematopoiesis in zebrafish.
AB  - CXXC finger protein 1 (CFP1) binds to unmethylated CpG dinucleotides and is a
      component of the Set1 histone methyltransferase complex. Mice lacking CFP1 suffer
      a peri-implantation lethal phenotype, and CFP1-deficient embryonic stem cells are
      viable but unable to differentiate and exhibit a 60-80% decrease in genomic
      cytosine methylation. A zebrafish homolog of CFP1 has been identified, is
      approximately 70% similar to murine CFP1, and is widely expressed during
      development. Zebrafish embryos treated with a zCFP1 antisense morpholino
      oligonucleotide had little or no circulating red blood cells and exhibited
      abnormal yolk sac morphology at 48 h post-fertilization. Many of the antisense
      treated zebrafish also exhibited cardiac edema, and 14% were dead at 24 h post
      fertilization. Morphant zebrafish also exhibited elevated levels of apoptosis,
      particularly in the intermediate cell mass, the site of primitive erythropoiesis,
      as well as aberrations in vascular development. Genomic DNA isolated from
      morphant embryos exhibited a 60% reduction of global genomic cytosine
      methylation. A similar phenotype was observed with an independent zCFP1 antisense
      morpholino oligonucleotide, but not following injection of an unrelated control
      oligonucleotide. The morphant phenotype was rescued when mRNA encoding murine
      CFP1 was co-injected with the antisense oligonucleotide. Genomic data base
      analysis reveals the presence of a second version of zebrafish CFP1 (zCFP1b).
      However, the morphant phenotype observed following specific depletion of zCFP1
      indicates that these related genes have nonredundant functions controlling normal
      zebrafish hematopoiesis and epigenetic regulation. These findings establish the
      importance of CFP1 during postgastrulation development.

PMID- 17023432
TI  - Changes in C-terminal binding protein 2 (CtBP2) corepressor complex induced by
      E1A and modulation of E1A transcriptional activity by CtBP2.
AB  - The N-terminal region of adenovirus E1A interacts with histone acetyl
      transferases (HATs) such as p300, P/CAF, and GCN5. The C-terminal region
      interacts with the transcriptional corepressors CtBP1 and CtBP2. The functional
      significance of co-recruitment of HATs and CtBPs by E1A is not well understood.
      In this study, we have shown that E1A enhanced acetylation of CtBP2 by
      recruitment of p300 to the CtBP2 complex. Additionally, E1A also displaced the
      histone methyltransferase G9a and the E-box repressor ZEB from the CtBP2 complex
      through the C-terminal CtBP-binding domain. A transcriptional activation function
      encoded by the E1A N-terminal region was efficiently inhibited by CtBP2 but not
      by a mutant with an N-terminal deletion or by a mutant deficient in interaction
      with E1A. Two isoforms of CtBP1 (CtBP1-L and CtBP1-S) poorly inhibited
      transcriptional activity of the E1A N-terminal region. Thus, the N-terminal
      domain of CtBP2 may contribute a unique transcriptional regulatory activity of
      CtBP2. Our results provide new insights by which CtBP might modulate the
      biochemical activities of E1A.

PMID- 17023433
TI  - MEKK1 is required for MPK4 activation and regulates tissue-specific and
      temperature-dependent cell death in Arabidopsis.
AB  - Innate immunity signaling pathways in both animals and plants are regulated by
      mitogen-activated protein kinase (MAPK) cascades. An Arabidopsis MAPK cascade
      (MEKK1, MKK4/MKK5, and MPK3/MPK6) has been proposed to function downstream of the
      flagellin receptor FLS2 based on biochemical assays using transient
      overexpression of candidate components. To genetically test this model, we
      characterized two mekk1 mutants. We show here that MEKK1 is not required for
      flagellin-triggered activation of MPK3 and MPK6. Instead, MEKK1 is essential for
      activation of MPK4, a MAPK that negatively regulates systemic acquired
      resistance. We also showed that MEKK1 negatively regulates temperature-sensitive
      and tissue-specific cell death and H(2)O(2) accumulation that are partly
      dependent on both RAR1, a key component in resistance protein function, and SID2,
      an isochorismate synthase required for salicylic acid production upon pathogen
      infection.

PMID- 17023434
TI  - Mental health screening in armed forces before the Iraq war and prevention of
      subsequent psychological morbidity: follow-up study.
AB  - OBJECTIVE: To assess whether screening for mental disorder before the start of
      the 2003 Iraq war would have predicted subsequent mental disorders. DESIGN:
      Longitudinal cohort study of the United Kingdom armed forces. PARTICIPANTS: 2820
      of 2873 personnel of the three services who completed an initial questionnaire in
      2002 were asked to complete a second questionnaire between June 2004 and 2 March
      2006. SETTING: Regiments, air stations, bases, ships, and homes for those who had
      left the services. MAIN OUTCOME MEASURES: Positive and negative likelihood
      ratios, and positive and negative predictive value of first assessment compared
      with assessment two to three years later of post-traumatic stress disorder,
      general health questionnaire, physical symptoms, self perception of health, and
      alcohol misuse for the entire group and for those deployed to the Iraq war.
      RESULTS: The response rate to the follow-up questionnaire was 69%, adjusted for
      return to senders. The positive likelihood ratio of post-traumatic stress
      disorder was high (13.1, 95% confidence interval 7.2 to 23.8), but the negative
      likelihood ratio was close to 1 (0.78, 0.67 to 0.91). The positive predictive
      values were low because of the low prevalence of post-traumatic stress disorder
      in the period before the Iraq war. The positive likelihood ratios for the other
      psychological assessments varied between 2.7 and 5.6, and the negative likelihood
      ratios were slightly lower than for post-traumatic stress disorder, indicating
      that these were not good candidates for screening. Results were the same for the
      analyses restricted to those who were deployed. CONCLUSIONS: Screening for common
      mental disorders before deployment in this cohort would not have reduced
      subsequent morbidity or predicted post-traumatic stress disorder, but this may
      change if there is a considerable increase in the prevalence of the disorder.

PMID- 17023435
TI  - Effect of beta radiation on success of glaucoma drainage surgery in South Africa:
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate whether beta radiation may offer a practical method of
      improving surgical success for glaucoma drainage surgery in South Africa. DESIGN:
      Double blind, randomised controlled trial. SETTING: Three public hospitals in
      South Africa. PARTICIPANTS: 450 black Africans with primary glaucoma.
      INTERVENTIONS: Trabeculectomy with 1000 cGy beta radiation or standard
      trabeculectomy without beta radiation (placebo). MAIN OUTCOME MEASURES: Primary
      outcome measure was surgical failure within 12 months (intraocular pressure > 21
      mm Hg while receiving no treatment for ocular hypotension). Secondary outcomes
      were visual acuity, surgical reintervention for cataract, and intraoperative and
      postoperative complications. RESULTS: 320 people were recruited. beta radiation
      was given to 164; 20 (6%) were not seen again after surgery. One year after
      surgery the estimated risk of surgical failure was 30% (95% confidence interval
      22% to 38%) in the placebo arm compared with 5% (2% to 10%) in the radiation arm.
      The radiation group experienced a higher incidence of operable cataract (18
      participants) than the placebo group (five participants; P = 0.01). At two years
      the estimated risks with placebo and beta radiation were, respectively, 2.8%
      (0.9% to 8.3%) and 16.7% (10.0% to 27.3%). CONCLUSION: beta radiation
      substantially reduced the risk of surgical failure after glaucoma surgery. Some
      evidence was, however, found of an increased risk for cataract surgery (a known
      complication of trabeculectomy) in the beta radiation arm during the two years
      after surgery. TRIAL REGISTRATION: ISRCTN62430622 [controlled-trials.com].

PMID- 17023436
TI  - Serological tests for visceral leishmaniasis.

PMID- 17023437
TI  - Combining aspirin with antithrombotic agents.

PMID- 17023438
TI  - Morbidity and mortality after emergency surgery.

PMID- 17023439
TI  - New arrhythmias after non-cardiothoracic surgery.

PMID- 17023440
TI  - Two and a bit cheers for academic medicine.

PMID- 17023441
TI  - Industry group suspends drug company for breaching code.

PMID- 17023442
TI  - Work on RNA interference brings Nobel triumph.

PMID- 17023447
TI  - Drug companies' lobbying of ministers has little effect on NICE.

PMID- 17023446
TI  - Italy debates end of life decisions.

PMID- 17023448
TI  - NICE approves docetaxel for early breast cancer.

PMID- 17023454
TI  - Influenza vaccine is delayed by problems in growing virus strain.

PMID- 17023455
TI  - Scottish scientists hope to supply human stem cells at low cost in 2007.

PMID- 17023458
TI  - Air pollution is a major threat to health, says WHO.

PMID- 17023461
TI  - Age should not determine treatment for anaemia in kidney disease.

PMID- 17023464
TI  - US judge allows class action over light cigarettes.

PMID- 17023465
TI  - How to measure renal function in clinical practice.

PMID- 17023466
TI  - The patient's journey: glaucoma.

PMID- 17023467
TI  - ABC of obesity. Management: Part I--behaviour change, diet, and activity.

PMID- 17023468
TI  - Payment for living organ donation should be legalised.

PMID- 17023470
TI  - NHS reorganisations: who's kicking whom, who's protesting? Where are the medical
      voices raised in protest: fit for the future?

PMID- 17023469
TI  - Trust, competence, and the supervisor's role in postgraduate training.

PMID- 17023471
TI  - NHS reorganisations: who's kicking whom, who's protesting? Will and power.

PMID- 17023472
TI  - NHS reorganisations: who's kicking whom, who's protesting? Nothing surprising is
      happening.

PMID- 17023473
TI  - NHS reorganisations: who's kicking whom, who's protesting? NHS is not short for
      National Health Service.

PMID- 17023474
TI  - Caesarean delivery in the second stage of labour: revisit the past.

PMID- 17023475
TI  - Caesarean delivery in the second stage of labour: consider the value of a
      functionally intact perineum.

PMID- 17023476
TI  - NHS reorganisations: who's kicking whom, who's protesting? More patient choice
      with less doctor choice is bad for everybody.

PMID- 17023477
TI  - Emergency naloxone for heroin overdose: naloxone is not the only opioid
      antagonist.

PMID- 17023478
TI  - Emergency naloxone for heroin overdose: beware of naloxone's other
      characteristics.

PMID- 17023479
TI  - Emergency naloxone for heroin overdose: over the counter availability needs
      careful consideration.

PMID- 17023480
TI  - Ageism in services for transient ischaemic attack and stroke: whose ageism?

PMID- 17023481
TI  - Recredentialling in New Zealand may inform UK recertification.

PMID- 17023482
TI  - Poor prescribing is continual.

PMID- 17023483
TI  - Emergency contraception is not just for the morning after.

PMID- 17023484
TI  - Chelation therapy and autism.

PMID- 17023485
TI  - S100B protein expression in the amnion and amniotic fluid in pregnancies
      complicated by pre-eclampsia.
AB  - Our aim was to investigate the expression of S100B protein in the amnion and to
      assess the amniotic fluid concentration in pregnancies complicated by pre
      eclampsia. Samples were obtained from women who developed pre-eclampsia (n = 7),
      pre-eclampsia with intrauterine growth retardation (IUGR) (n = 4), normotensive
      IUGR (n = 7) and gestational hypertension (n = 4) during pregnancy and healthy
      controls who delivered at term (n = 35). To determine the difference in the
      expression of S100B in the amnion, we performed immunohistochemistry, western
      blot analysis and RT-PCR. Using enzyme-linked immunosorbent assay (ELISA), we
      assessed the S100B concentration in amniotic fluid. The S100B mRNA expression in
      the amnion of pre-eclamptic patients and patients with pre-eclampsia with IUGR
      was significantly higher than that in the control. The amniotic fluid S100B
      protein concentration of the pre-eclampsia and normotensive IUGR cases was
      significantly higher than that of the control. This study shows that amnion could
      be a source responsible for the increased concentration of S100B in amniotic
      fluid. In pre-eclampsia, reactive oxygen species (ROS) are generated by oxidative
      stress. Some pathological conditions that develop during pregnancy and are
      related to hypoxic stress can affect the elevation of S100B concentration in the
      amnion.

PMID- 17023486
TI  - Antibody binding loop insertions as diversity elements.
AB  - In the use of non-antibody proteins as affinity reagents, diversity has generally
      been derived from oligonucleotide-encoded random amino acids. Although specific
      binders of high-affinity have been selected from such libraries, random
      oligonucleotides often encode stop codons and amino acid combinations that affect
      protein folding. Recently it has been shown that specific antibody binding loops
      grafted into heterologous proteins can confer the specific antibody binding
      activity to the created chimeric protein. In this paper, we examine the use of
      such antibody binding loops as diversity elements. We first show that we are able
      to graft a lysozyme-binding antibody loop into green fluorescent protein (GFP),
      creating a fluorescent protein with lysozyme-binding activity. Subsequently we
      have developed a PCR method to harvest random binding loops from antibodies and
      insert them at predefined sites in any protein, using GFP as an example. The
      majority of such GFP chimeras remain fluorescent, indicating that binding loops
      do not disrupt folding. This method can be adapted to the creation of other
      nucleic acid libraries where diversity is flanked by regions of relative sequence
      conservation, and its availability sets the stage for the use of antibody loop
      libraries as diversity elements for selection experiments.

PMID- 17023488
TI  - Semen quality in a residential, geographic and age representative sample of
      healthy Chinese men.
AB  - BACKGROUND: Population-based study of semen quality is rare in literature.
      METHODS: Healthy men aged 20-60 years from six Chinese provinces were invited to
      participate in the study between December 2000 and November 2002. Posters were
      distributed in the participating counties to enroll 200 subjects from each
      province. Medians, percentiles, and proportions below lower threshold of the WHO
      criteria for semen parameters were calculated. Generalized linear models were
      used to examine the determinants of semen quality. RESULTS: Semen samples from
      1191 healthy Chinese men were collected and analysed. The medians (5th and 95th
      percentiles) were 2.3 ml (1.0-4.5) for semen volume, 65 x 10(6)/ml (20-150) for
      semen concentration, 154 x 10(6)/ejection (29-421) for sperm count, 19% (5-32)
      for rapid progressive motility, 46% (29-66) for progressive motility, 67% (47-81)
      for total motile spermatozoa, 70% (48-88) for sperm viability and 39% (23-76) for
      normal morphology. Many healthy Chinese men had semen parameter values below the
      lower threshold of the WHO criteria. Region, age, abstinence duration and season
      were important determinants of semen quality. CONCLUSIONS: Chinese men have lower
      values of semen parameters according to WHO standard, and a lower threshold for
      normal semen parameters for Chinese men should be considered.

PMID- 17023487
TI  - Different modes and potencies of translational repression by sequence-specific
      RNA-protein interaction at the 5'-UTR.
AB  - To determine whether sequence-specific RNA-protein interaction at the 5'
      untranslated region (5'-UTR) can potently repress translation in mammalian cells,
      a bicistronic translational repression assay was developed to permit direct
      assessment of RNA-protein interaction and translational repression in transiently
      transfected living mammalian cells. Changes in cap-dependent yellow fluorescent
      protein (YFP) and internal ribosome entry sequence (IRES)-dependent cyan
      fluorescent protein (CFP) translation were monitored by fluorescence microscopy.
      Selective repression of YFP or coordinate repression of both YFP and CFP
      translation occurred, indicating two distinct modes by which RNA-binding proteins
      repress translation through the 5'-UTR. Interestingly, a single-stranded RNA
      binding protein from Bacillus subtilis, tryptophan RNA-binding attenuation
      protein (TRAP), showed potent translational repression, dependent on the level of
      TRAP expression and position of its cognate binding site within the bicistronic
      reporter transcript. As the first of its class to be examined in mammalian cells,
      its potency in repression of translation through the 5'-UTR may be a general
      feature for this class of single-stranded RNA-binding proteins. Finally, a one
      hybrid screen based on translational repression through the 5'-UTR identified
      linkers supporting full-translational repression as well as a range of partial
      repression by TRAP within the context of a fusion protein.

PMID- 17023489
TI  - Effect of laparoscopic ovarian diathermy on circulating inhibin B in women with
      anovulatory polycystic ovary syndrome.
AB  - BACKGROUND: Laparoscopic ovarian diathermy (LOD) frequently induces ovulation in
      patients with polycystic ovary syndrome (PCOS). The mechanism by which this
      effect occurs remains largely unexplained. The aim of this study was to measure
      changes in inhibin B production in response to LOD to see whether this could
      explain the mechanism of action of LOD. METHODS: This prospective study included
      50 anovulatory women with PCOS. All women underwent LOD. Blood samples were
      collected before and after LOD to measure plasma concentrations of inhibin B,
      gonadotrophins and androgens. RESULTS: The pre-operative median plasma
      concentration of inhibin B was 110.0 pg/ml (range 19.0-567.0 pg/ml). There was a
      statistically significant inverse correlation (r= -0.286; P < 0.05) between body
      mass index (BMI) and inhibin B. Non-obese women with PCOS (BMI <or= 30 kg/m2;
      n=37) displayed significantly (P < 0.05) higher plasma inhibin B concentrations
      [122.0 pg/ml (range 19.0-567.0 pg/ml)] compared with those [51.0 pg/ml (range
      27.0-201.0 pg/ml)] of obese PCOS women (BMI > 30 kg/m2; n=13). Following LOD, 39
      women ovulated. No statistically significant change of inhibin B after LOD was
      observed in the overall group of women with PCOS or in the subgroup of non-obese
      PCOS women with higher pre-operative inhibin B. CONCLUSIONS: The lack of any
      change of inhibin B after LOD makes it unlikely that this hormone has any role to
      play in the mechanism of action of LOD.

PMID- 17023490
TI  - Does subfertility explain the risk of poor perinatal outcome after IVF and
      ovarian hyperstimulation?
AB  - BACKGROUND: The primary objective of this study was to investigate whether
      subfertility explains poor perinatal outcome after assisted conception. A
      secondary objective was to test the hypothesis that ovarian hyperstimulation
      rather than the IVF procedure may influence the perinatal outcome. METHODS: Using
      data from a Dutch population-based historical cohort of women treated for
      subfertility, we compared perinatal outcome of singletons conceived after
      controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with
      perinatal outcome in subfertile women who conceived spontaneously (subfertile
      controls; n = 6343) and in women who only received COHS (COHS only; n = 84).
      Furthermore, we compared perinatal outcome of singletons conceived after the
      transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim -
      Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g)
      and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9
      3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the
      subfertile control group. The ORs for very preterm birth (<32 weeks) and for
      preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8),
      respectively. Adjustment for confounders did not materially change these risk
      estimates. The difference in risk between the COHS-only group and the subfertile
      group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4),
      but the association became weaker after adjustment for maternal age and
      primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight
      and preterm delivery was found between the group of children conceived after
      ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of
      children conceived after embryo transfer of thawed embryos in a spontaneous cycle
      without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The
      poor perinatal outcome in this database could not be explained by subfertility
      and suggests that other factors may be important in the known association between
      assisted conception and poor perinatal outcome.

PMID- 17023491
TI  - Cell therapy for renal regeneration--time for some joined-up thinking?

PMID- 17023492
TI  - A prospective multicentre study of the role of anaemia as a risk factor in
      haemodialysis patients: the MAR Study.
AB  - BACKGROUND: Retrospective studies have shown hospitalization and mortality rates
      during haemodialysis (HD) to be associated with anaemia. METHODS: The
      prospective, multicentre Morbidity-and-mortality Anaemia Renal (MAR) study was
      designed to establish the burden of anaemia by controlling for other risk
      factors. Charlson index was used for comorbid adjustment. Finally, 1428 patients
      from 119 centres (60% men, aged 64.4 years, time on HD 15.3 months, Charlson
      comorbidity index 6.5 +/- 2.3) completed follow-up. They had hypertension
      (75.8%), diabetes mellitus (25.9%), heart failure (13.9%) and coronary disease
      (16.7%). Of the total patients, 94.8% were receiving erythropoietin (111.6 +/-
      70.6 U/kg/week) and 76.7% i.v. iron, and haemoglobin (Hb) at inclusion was 11.7
      +/- 1.5 g/dl. RESULTS: Hospitalization rate was 1.1 admissions/patient/year.
      Yearly mortality was 12% [35% cardiovascular (CV)]. The relative risk and
      confidence interval (CI) for hospitalization and death were 0.86 (0.81-0.91) and
      0.82 (0.73-0.91), respectively, per 1 g/dl increase in initial Hb after
      adjustment for comorbidity, vintage, aetiology, access type, albumin and Kt/V.
      The probability of remaining free from hospitalization (CI) was 0.34 (0.27-0.41)
      for initial Hb <10 g/dl, 0.47 (0.41-0.53) for Hb 10-11 g/dl, 0.54 (0.49-0.59) for
      Hb 11-12 g/dl, and 0.63 (0.59-0.67) for Hb >12 g/dl. Same analysis for patient
      survival was 0.77 (0.71-0.83) for Hb <10 g/dl vs 0.82 (0.77-0.87) for Hb 10-11 vs
      0.89 (0.86-0.92) for Hb 11-12 vs 0.92 (0.90-0.94) for Hb > 12 g/dl, P < 0.001.
      The Cox regression model for hospitalization-free survival included the risk
      factors initial Hb (relative risk 0.86 per 1 g/dl increase, P < 0.001) Charlson,
      albumin and prior CV event. CONCLUSION: Hb level predicted 1-year-survival and
      hospitalization. This effect persisted after adjustment for comorbidity and other
      prognostic factors.

PMID- 17023493
TI  - Secondary rise of albuminuria under AT1-receptor blockade--what is the potential
      role of aldosterone escape?

PMID- 17023494
TI  - Sleep apnoea in end-stage renal disease: a short review of mechanisms and
      potential benefit from its treatment.

PMID- 17023495
TI  - Cognitive impairment in chronic kidney disease.
AB  - BACKGROUND: Although end-stage renal disease (ESRD) has been associated with
      cognitive impairment, the relation between lesser degrees of chronic kidney
      disease (CKD) and cognitive impairment is less well understood. The objective of
      this study was to assess the cognitive function in patients with varying severity
      of CKD using P3 event-related potentials (P3ERPs). METHODS: In this cross
      sectional study, 15 neurologically asymptomatic (Mini Mental State Examination
      >24) patients each of CKD stage 3, 4 and 5 (undialysed) were enrolled. Besides
      this, 15 healthy controls were also studied. All groups were age and sex matched.
      Glomerular filtration rate (GFR) was estimated using the Modification of Diet in
      Renal Disease equation. The P300 was studied in all subjects by using standard
      auditory 'odd-ball' paradigm and the data obtained were statistically analysed.
      RESULTS: We noted significant prolongation of P300 latencies as severity of CKD
      increased from stage 3 (318.8 +/- 28.98 ms) to stage 4 (357 +/- 24.65 ms) (P <
      0.002) and from stage 4 to 5 (388.47 +/- 31.67 ms) (P < 0.01). P300 latency in
      CKD stage 3 was not found to be significantly different from controls (308.4 +/-
      13.73 ms). Significant positive correlation was noted between serum creatinine,
      blood urea and uric acid with P3 latency. Significant negative correlation was
      noted between GFR, serum calcium and haemoglobin with P3 latency. CONCLUSIONS:
      Increasing severity of CKD is associated with progressive cognitive decline and
      this may have important clinical consequences.

PMID- 17023496
TI  - Detection of Escherichia coli harbouring extended-spectrum beta-lactamases of the
      CTX-M, TEM and SHV classes in faecal samples of wild animals in Portugal.

PMID- 17023497
TI  - Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant
      Campylobacter under selection pressure.
AB  - OBJECTIVES: The objective of this study was to determine the contribution of the
      CmeABC efflux pump to the emergence of fluoroquinolone (FQ)-resistant mutants in
      Campylobacter jejuni under various levels of selection pressure. METHODS: The
      frequency of emergence of ciprofloxacin-resistant mutants was measured in wild
      type C. jejuni NCTC 11168 and its isogenic cmeB mutant and cmeR mutant
      (overexpressing cmeABC) using plates containing various concentrations of
      ciprofloxacin. Representative ciprofloxacin-resistant mutants were selected for
      gyrA sequence analysis and MIC determination. Accumulation of ciprofloxacin in
      Campylobacter cells was measured using spectrofluorometry. RESULTS: Mutation of
      cmeB drastically reduced the frequency of emergence of FQ-resistant mutants at
      10x and 32x the MIC of ciprofloxacin, while the cmeR mutant displayed an
      approximately 17-fold increase in the frequency of emergence of the mutants at
      32x the MIC when compared with the wild-type strain. Various point mutations
      occurred in gyrA in the FQ-resistant mutants selected at 5x and 10x the MIC,
      while the Thr-86-->Ile mutation was predominant in the mutants selected at 32x
      the MIC. The Thr-86-->Ile change conferred a high-level resistance to FQs, but
      other mutations only conferred an intermediate-level FQ resistance. In contrast,
      all types of gyrA mutations in the CmeABC-overexpressed background conferred high
      level resistance to ciprofloxacin. Overexpression of cmeABC significantly reduced
      the amount of ciprofloxacin accumulated within bacterial cells. CONCLUSIONS:
      CmeABC is not only important for maintaining high-level resistance to FQs but
      also contributes significantly to the emergence of FQ-resistant mutants.
      Inhibition of this efflux pump may prevent the emergence of clinically relevant
      FQ-resistant Campylobacter mutants.

PMID- 17023498
TI  - Explaining variability in the relationship between antiretroviral adherence and
      HIV mutation accumulation.
AB  - OBJECTIVES: Determining the relationship between antiretroviral adherence and
      resistance accumulation is important for the design and evaluation of adherence
      interventions. Our objective was to explain heterogeneity observed in this
      relationship. METHODS: We first conducted a systematic review to locate published
      reports describing the relationship between adherence and resistance. We then
      used a validated computer simulation to simulate the patient populations in these
      reports, exploring the impact of changes in individual patient characteristics
      (age, CD4, viral load, prior antiretroviral experience) on the shape of the
      adherence-resistance (A-R) curve. RESULTS: The search identified 493 titles, of
      which 3 contained relevant primary data and 2 had sufficient follow-up for
      inclusion (HOMER and REACH cohorts). When simulating HOMER, the A-R curve had a
      high peak with a greatly increased hazard ratio (HR) of accumulating mutations at
      partial compared to complete adherence (simulation, HR 2.9; HOMER, HR 2.7). When
      simulating REACH, the A-R curve had a shallow peak with a slightly increased
      hazard of accumulating mutations at partial adherence (simulation, HR 1.2; REACH,
      HR 1.4). This heterogeneity was primarily attributable to differences in
      antiretroviral experience between the cohorts. CONCLUSIONS: Our computer
      simulation was able to explain much of the heterogeneity in observed A-R curves.

PMID- 17023499
TI  - Fungicidal activity of five cathelicidin peptides against clinically isolated
      yeasts.
AB  - OBJECTIVES: To investigate the in vitro antifungal activity of the structurally
      different cathelicidin peptides SMAP-29, BMAP-27, BMAP-28, protegrin-1 (PG-1) and
      indolicidin. METHODS: The in vitro antifungal and fungicidal activities of these
      antimicrobial peptides were respectively assessed via MIC determinations and
      killing kinetics assays. The effects of the peptides on membrane permeabilization
      and morphology were evaluated by flow cytometry, intracellular ATP release
      measurements and scanning electron microscopy. RESULTS: All five peptides showed
      a potent but differential antifungal activity against more than 70 clinical
      isolates belonging to over 20 different species of pathogenic fungi; some of
      which are resistant to amphotericin B and azoles. The MIC values of the peptides
      ranged between 0.5 and 32 microM, with PG-1 being the most effective and having
      the widest spectrum of activity. Filamentous fungi were instead found to be
      scarcely susceptible to the action of these cathelicidin peptides. All these
      cathelicidins rapidly killed Candida albicans and Cryptococcus neoformans cells
      in a dose- and time-dependent manner. The rapid uptake of propidium iodide into
      treated cells and morphological alterations apparent on their cellular surfaces
      suggest a killing mechanism based on membrane permeabilization and damage.
      CONCLUSIONS: This study indicates that these five structurally varied host
      defence peptides are all endowed with the capacity to inactivate a number of
      fungal pathogens, irrespectively of their resistance to antifungal drugs, and
      suggests they might be potentially useful leads for the development of novel
      fungicidal agents.

PMID- 17023500
TI  - A simple index to measure hygiene behaviours.
AB  - BACKGROUND: Spot checks are becoming a popular method to assess hygiene
      behaviours; however, little is known about their repeatability or predictability.
      We evaluated the within-household repeatability of hygiene indices created from
      spot checks and their ability to predict incidence of diarrhoea in young
      Guatemalan children. METHODS: We observed hygiene behaviours in 588 households in
      four rural Guatemalan communities over 36 months. Four indices related to
      drinking water (DWI; score = 0-3), food (FI; score = 0-3), personal hygiene (PHI;
      score = 0-3), and domestic household hygiene (DHI; score = 0-6) and one summary
      hygiene index (SHI; range 0-15) were created. Morbidity of 694 children aged
      birth to 36 months living in the study households was assessed using biweekly
      recall. Intraclass correlation coefficients were calculated to assess within
      household repeatability; the generalized estimating equations approach was
      employed to analyse diarrhoea morbidity. RESULTS: Households were observed a mean
      of 22.1 +/- 11.2 times. All indices decreased with duration of follow-up (SHI = 
      0.67 +/- 0.05 points/year; WI = -0.04 +/- 0.01; FI = -0.07 +/- 0.01; PHI = -0.21
      +/- 0.01; DHI = -0.37 +/- 0.02; all P < 0.05). Intraclass correlations were low
      to moderate (SHI = 0.35-0.51; DWI = 0.17-0.21; FI = 0.16-0.18; PHI = 0.27-0.32;
      DHI = 0.27-0.38). Six separate spot checks would be needed to estimate a
      household's underlying level of hygiene within 20%. SHI and PHI scores were
      inversely associated with diarrhoea morbidity (both P < 0.05). CONCLUSIONS:
      Hygiene indices created using spot checks can be a rapid and efficient method for
      assessing hygiene and useful for predicting diarrhoea morbidity in young
      children. Multiple measures are required to accurately estimate the true hygiene
      pattern of a household.

PMID- 17023501
TI  - Exercise pressor reflex function is altered in spontaneously hypertensive rats.
AB  - In hypertension, exercise elicits excessive elevations in mean arterial pressure
      (MAP) and heart rate (HR) increasing the risk for adverse cardiac events and
      stroke during physical activity. The exercise pressor reflex (a neural drive
      originating in skeletal muscle), central command (a neural drive originating in
      cortical brain centres) and the tonically active arterial baroreflex contribute
      importantly to cardiovascular control during exercise. Each of these inputs
      potentially mediates the heightened cardiovascular response to physical activity
      in hypertension. However, given that exercise pressor reflex overactivity is
      known to elicit enhanced circulatory responses to exercise in disease states
      closely related to hypertension (e.g. heart failure), we tested the hypothesis
      that the exaggerated cardiovascular response to exercise in hypertension is
      mediated by an overactive exercise pressor reflex. To test this hypothesis, we
      used a rat model of exercise recently developed in our laboratory that
      selectively stimulates the exercise pressor reflex independent of central command
      and/or the arterial baroreflex. Activation of the exercise pressor reflex during
      electrically induced static muscle contraction in the absence of input from
      central command resulted in significantly larger increases in MAP and HR in male
      spontaneously hypertensive rats as compared to normotensive Wistar-Kyoto rats
      over a wide range of exercise intensities. Similar findings were obtained in
      animals in which input from both central command and the arterial baroreflex were
      eliminated. These findings suggest that the enhanced cardiovascular response to
      exercise in hypertension is mediated by an overactive exercise pressor reflex.
      Potentially, effective treatment of exercise pressor reflex dysfunction may
      reduce the cardiovascular risks associated with exercise in hypertension.

PMID- 17023502
TI  - From the Hodgkin-Huxley axon to the virtual heart.
AB  - Experimentally based models of the heart have been developed since 1960, starting
      with the discovery and modelling of potassium channels. The early models were
      based on extensions of the Hodgkin-Huxley nerve impulse equations. The first
      models including calcium balance and signalling were made in the 1980s and have
      now reached a high degree of physiological detail. During the 1990s these cell
      models have been incorporated into anatomically detailed tissue and organ models
      to create the first virtual organ, the Virtual Heart. With over 40 years of
      interaction between simulation and experiment, the models are now sufficiently
      refined to begin to be of use in drug development.

PMID- 17023503
TI  - Extrasynaptic alphabeta subunit GABAA receptors on rat hippocampal pyramidal
      neurons.
AB  - Extrasynaptic GABA(A) receptors that are tonically activated by ambient GABA are
      important for controlling neuronal excitability. In hippocampal pyramidal
      neurons, the subunit composition of these extrasynaptic receptors may include
      alpha5betagamma and/or alpha4betadelta subunits. Our present studies reveal that
      a component of the tonic current in the hippocampus is highly sensitive to
      inhibition by Zn(2+). This component is probably not mediated by either
      alpha5betagamma or alpha4betadelta receptors, but might be explained by the
      presence of alphabeta isoforms. Using patch-clamp recording from pyramidal
      neurons, a small tonic current measured in the absence of exogenous GABA
      exhibited both high and low sensitivity to Zn(2+) inhibition (IC(50) values, 1.89
      and 223 microm, respectively). Using low nanomolar and micromolar GABA
      concentrations to replicate tonic currents, we identified two components that are
      mediated by benzodiazepine-sensitive and -insensitive receptors. The latter
      indicated that extrasynaptic GABA(A) receptors exist that are devoid of gamma2
      subunits. To distinguish whether the benzodiazepine-insensitive receptors were
      alphabeta or alphabetadelta isoforms, we used single-channel recording.
      Expressing recombinant alpha1beta3gamma2, alpha5beta3gamma2, alpha4beta3delta and
      alpha1beta3 receptors in human embryonic kidney (HEK) or mouse fibroblast (Ltk)
      cells, revealed similar openings with high main conductances (approximately 25-28
      pS) for gamma2 or delta subunit-containing receptors whereas alphabeta receptors
      were characterized by a lower main conductance state (approximately 11 pS).
      Recording from pyramidal cell somata revealed a similar range of channel
      conductances, indicative of a mixture of GABA(A) receptors in the extrasynaptic
      membrane. The lowest conductance state (approximately 11 pS) was the most
      sensitive to Zn(2+) inhibition in accord with the presence of alphabeta
      receptors. This receptor type is estimated to account for up to 10% of all
      extrasynaptic GABA(A) receptors on hippocampal pyramidal neurons.

PMID- 17023504
TI  - Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/Delta
      murine hearts modelling long QT syndrome 3.
AB  - Long QT3 (LQT3) syndrome is associated with incomplete Na+ channel inactivation,
      abnormal repolarization kinetics and prolonged cardiac action potential duration
      (APD). Electrophysiological effects of flecainide and quinidine were compared in
      Langendorff-perfused wild-type (WT), and genetically modified (Scn5a+/Delta)
      murine hearts modelling LQT3. Extra stimuli (S2) following trains of pacing
      stimuli (S1) applied to the right ventricular epicardium triggered ventricular
      tachycardia (VT) in 16 out of 28 untreated Scn5a+/Delta and zero out of 12 WT
      hearts. Paced electrogram fractionation analysis then demonstrated increased
      electrogram durations (EGD), expressed as EGD ratios, in arrhythmogenic
      Scn5a+/Delta hearts, and prolonged ventricular effective refractory periods in
      initially non-arrhythmogenic Scn5a+/Delta hearts. Nevertheless, comparisons of
      epicardial and endocardial monophasic action potential recordings demonstrated
      negative transmural repolarization gradients in both groups, giving DeltaAPD(90)
      values at 90% repolarization of -20.88 +/- 1.93 ms (n = 11) and -16.91 +/- 1.43
      ms (n = 23), respectively. Flecainide prevented initiation of VT in 13 out of 16
      arrhythmogenic Scn5a+/Delta hearts, reducing EGD ratio and restoring DeltaAPD90
      to + 7.55 +/- 2.24 ms (n = 9) (P < 0.05). VT occurred in four out of eight non
      arrhythmogenic Scn5a+/Delta hearts in the presence of quinidine, which increased
      EGD ratio but left DeltaAPD90 unchanged. In contrast (P < 0.05), WT hearts had
      positive DeltaAPD90 values (+ 11.72 +/- 2.17 ms) (n = 20). Flecainide then
      increased arrhythmic tendency and EGD ratio but conserved DeltaAPD90; reduced EGD
      ratios and unaltered DeltaAPD90 values accompanied the lower arrhythmogenicity
      associated with quinidine treatment. In addition to the changes in EGD ratio
      shown by WT hearts, these findings attribute arrhythmogenesis and its
      modification by flecainide and quinidine to alterations in DeltaAPD90 in
      Scn5a+/Delta hearts. This is consistent with a hypothesis in which incomplete Na+
      channel inactivation in Scn5a+/Delta hearts generates functional substrates
      dependent on altered refractoriness that cause abnormalities in activation and
      conduction of subsequent cardiac impulses. Any spatial heterogeneities between
      the epicardial and endocardial layers would thus cause fragmentation of the
      activation wavefront and contribute to electrogram spreading.

PMID- 17023505
TI  - Effects of solution tonicity on crossbridge properties and myosin lever arm
      disposition in intact frog muscle fibres.
AB  - The aims of this study were to investigate the effects of solution tonicity on
      muscle properties, and to verify their consistence with the lever arm theory of
      force generation. Experiments were made in single muscle fibres and in fibre
      bundles from the frog, using both fast stretches and time-resolved X-ray
      diffraction, in isotonic Ringer solution (1T), hypertonic (1.4T) and hypotonic
      (0.8T) solutions. Fast stretches (0.4-0.6 ms duration and 16-25 nm per half
      sarcomere (nm hs(-1)) amplitude) were applied at various tensions during the
      force development in isometric tetani. Force increased during the stretch up to a
      peak (critical tension, Pc) at which it started to fall, in spite of continued
      stretching. In all solutions, Pc was proportional to the initial isometric
      tension developed. For a given isometric tension, Pc increased with solution
      tonicity and occurred at a precise sarcomere elongation (critical length, Lc)
      which also increased with tonicity. M3 meridional layer line intensity (I M3) was
      measured during the application of sinusoidal length oscillations (1 kHz
      frequency, and about 2% fibre length amplitude) at tetanus plateau. I M3 changed
      during the length oscillations in a sinusoidal manner in phase opposition to
      length changes, but a double peak distortion occurred at the peak of the release
      phase. The presence of the distortion, which decreased with tonicity, allowed
      calculation of the mean position of the myosin head (S1) during the oscillation
      cycle. In agreement with the lever arm theory, both X-ray diffraction and
      mechanical data show that solution tonicity affects S1 mean position and
      consequently crossbridge individual extension and force, with no effect on
      crossbridge number. The force needed to break the single crossbridge was
      insensitive to solution tonicity suggesting a non-ionic nature of the actomyosin
      bond.

PMID- 17023506
TI  - Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity
      impairments in the visual cortex.
AB  - In the present report, we focused our attention on the role played by the
      muscarinic acetylcholine receptors (mAChRs) in different forms of long-term
      synaptic plasticity. Specifically, we investigated long-term potentiation (LTP)
      and long-term depression (LTD) expression elicited by theta-burst stimulation
      (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical
      slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked
      in M(1)/M(3) double KO mice, while LTP was impaired in the M(2)/M(4) double KO
      animals. On the other hand, LFS induced LTD in M(2)/M(4) double KO mice, but
      failed to do so in M(1)/M(3) KO mice. Interestingly, LFS produced LTP instead of
      LTD in M(1)/M(3) KO mice. Analysis of mAChR single KO mice revealed that LTP was
      affected only by the simultaneous absence of both M(2) and M(4) receptors. A LFS
      dependent shift from LTD to LTP was also observed in slices from M(1) KO mice,
      while LTD was simply abolished in slices from M(3) KO mice. Using pharmacological
      tools, we showed that LTP in control mice was blocked by pertussis toxin, an
      inhibitor of G(i/o) proteins, but not by raising intracellular cAMP levels. In
      addition, the inhibition of phospholipase C by U73122 induced the same shift from
      LTD to LTP after LFS observed in M(1) single KO and M(1)/M(3) double KO mice. Our
      results indicate that different mAChR subtypes regulate different forms of long
      term synaptic plasticity in the mouse visual cortex, activating specific G
      proteins and downstream intracellular mechanisms.

PMID- 17023508
TI  - Velocity recovery cycles of single C fibres innervating rat skin.
AB  - To improve knowledge about axonal membrane properties in nociceptive and non
      nociceptive C fibres, we studied impulse-dependent velocity changes by in vivo
      microneurography in the rat sciatic nerve. Cutaneous C fibres were classified,
      based primarily on their activity-dependent slowing profile, as Type 1A (mechano
      responsive nociceptors; CMR; n = 23), Type 1B (mechano-insensitive nociceptors;
      CMI; n = 24), Type 2 (cold units; n = 2), Type 3 units (unknown function; n = 4)
      or Type 4 (presumed sympathetics; n = 23) units. They were excited by single,
      double and triple electrical stimuli to the skin at mean rates of 0.25, 0.5, 1
      and 2 Hz and with interstimulus intervals ranging from 2 to 1000 ms. All CMRs
      exhibited only postspike subnormality at 0.25 and 0.5 Hz. They gradually
      developed supernormality with higher stimulation rates, and 12/19 CMRs were
      supernormal at 1 Hz. The CMIs showed a greater tendency towards supernormality,
      with 10/21 already supernormal at 0.25 Hz, 17/24 at 0.5 Hz and all were
      supernormal at 1 Hz. In some CMIs but in none of the CMRs, the supernormal period
      was directly followed by a peak in late subnormality. Among non-nociceptive
      fibres, all Type 4 units exhibited long-lasting supernormality independent of the
      stimulation rate, whereas the cold units showed short-lived supernormality. In
      both, supernormality increased with higher stimulation rates. Regardless of fibre
      function or stimulation rate, a second conditioning stimulus always induced
      additional slowing, providing evidence for a passive origin of supernormality in
      all rat C fibre subtypes. However, the degree and time-course of extra slowing
      due to a preconditioning stimulus was highly dependent on fibre function and
      stimulation rate. These data indicate axonal membrane differences between
      different functional classes of C fibres, which resemble those previously
      described in human C fibres.

PMID- 17023507
TI  - Transcranial direct current stimulation of the primary motor cortex affects
      cortical drive to human musculature as assessed by intermuscular coherence.
AB  - Intermuscular coherence analysis can be used to assess the common drive to
      muscles. Coherence in the beta-frequency band (15-35 Hz) is thought to arise from
      common cortical sources. Intermuscular coherence analysis is a potentially
      attractive tool for the investigation of motor cortical excitability changes
      because it is non-invasive and can be done relatively quickly. We carried out
      this study to test the hypothesis that intermuscular coherence analysis was able
      to detect cortical excitability changes in healthy subjects following
      transcranial direct current stimulation (tDCS). tDCS has been shown to increase
      (anodal stimulation) or decrease (cathodal stimulation) the size of the muscle
      potential evoked by TMS. We found that anodal tDCS caused an increase in motor
      evoked potential (MEP) size that was paralleled by an increase in beta-band
      intermuscular coherence. Similarly, the reduction in MEP size produced by
      cathodal tDCS was paralleled by a reduction in beta-band intermuscular coherence,
      while sham stimulation did not result in any change in either MEP amplitude or
      beta-band intermuscular coherence. The similar pattern of change observed for MEP
      and intermuscular coherence may indicate similar mechanisms of action, although
      this cannot be assumed without further investigation. These changes do suggest
      that at least some of the action of tDCS is on cortical networks, and that
      combined tDCS and intermuscular coherence analysis may be useful in the diagnosis
      of pathologies affecting motor cortical excitability.

PMID- 17023509
TI  - Bone loss from the human distal tibia epiphysis during 24 days of unilateral
      lower limb suspension.
AB  - Bone loss during immobilization is well documented. Currently, the only means of
      studying this in human beings is bed rest, which is resource intensive and
      inconvenient for the subjects. Unilateral lower limb suspension (ULLS) has been
      suggested as an alternative, but has not previously been demonstrated to cause
      bone loss. The main aim of our study was to test the hypothesis that ULLS would
      cause bone loss determined by peripheral quantitative computed tomography (pQCT).
      We investigated eight young healthy volunteers (19.1 +/- 0.7 years; body mass
      index, 22.4 +/- 2.6 kg m(-2)), who underwent ULLS for 24 days; their right foot
      was suspended with a strap attached to the shoulder so the knee angle was 10 deg
      and they wore a left shoe with a 7.5 cm sole to allow clearance of the right foot
      and used bilateral crutches to perambulate. Bone scans were obtained by pQCT from
      the distal epiphyses and from the diaphyses of the tibia in each leg twice before
      suspension, at days 7, 14 and 21 of the ULLS, and at days 4, 9, 35 and 90 of
      recovery. After 21 days of ULLS, bone mineral content of the peripheral portion
      of the epiphysis of the suspended tibia was reduced by 0.89 +/- 0.48% (from 280.9
      +/- 34.5 to 278.4 +/- 34.2 mg mm(-1), P < 0.001) but no changes were observed in
      its central portion or in the unsuspended tibia. In the peripheral epiphyseal
      portion, significant bone loss (by 0.32 +/- 0.54%, P = 0.045) occurred as early
      as day 7 of ULLS. We have demonstrated, for the first time, that in humans bone
      is lost during ULLS at rates comparable to those seen with bed rest, without
      alteration in limb fluid volumes thus validating the technique and raising
      important questions about the mechanisms involved.

PMID- 17023510
TI  - Kinematics and eye-head coordination of gaze shifts evoked from different sites
      in the superior colliculus of the cat.
AB  - Shifting gaze requires precise coordination of eye and head movements. It is
      clear that the superior colliculus (SC) is involved with saccadic gaze shifts.
      Here we investigate its role in controlling both eye and head movements during
      gaze shifts. Gaze shifts of the same amplitude can be evoked from different SC
      sites by controlled electrical microstimulation. To describe how the SC
      coordinates the eye and the head, we compare the characteristics of these
      amplitude-matched gaze shifts evoked from different SC sites. We show that
      matched amplitude gaze shifts elicited from progressively more caudal sites are
      progressively slower and associated with a greater head contribution. Stimulation
      at more caudal SC sites decreased the peak velocity of the eye but not of the
      head, suggesting that the lower peak gaze velocity for the caudal sites is due to
      the increased contribution of the slower-moving head. Eye-head coordination
      across the SC motor map is also indicated by the relative latencies of the eye
      and head movements. For some amplitudes of gaze shift, rostral stimulation evoked
      eye movement before head movement, whereas this reversed with caudal stimulation,
      which caused the head to move before the eyes. These results show that gaze
      shifts of similar amplitude evoked from different SC sites are produced with
      different kinematics and coordination of eye and head movements. In other words,
      gaze shifts evoked from different SC sites follow different amplitude-velocity
      curves, with different eye-head contributions. These findings shed light on
      mechanisms used by the central nervous system to translate a high-level motor
      representation (a desired gaze displacement on the SC map) into motor commands
      appropriate for the involved body segments (the eye and the head).

PMID- 17023512
TI  - Identification of CXCR4 as a new nitric oxide-regulated gene in human CD34+
      cells.
AB  - As an intracellular second messenger, nitric oxide (NO) is increasingly
      implicated in the control of transcriptional machinery and gene expression. Here,
      we show that cell surface expression of CXCR4 on CD34(+) cells was increased in a
      dose- and time-dependent manner in response to NO donors. Augmented surface
      expression was correlated with an increase in CXCR4 mRNA level. A specific NO
      scavenger prevented the elevation in CXCR4 mRNA caused by NO donors, suggesting a
      direct signaling action mediated by NO on CXCR4 transcription. NO treatment had
      no significant effect on CXCR4 mRNA stability. However, induction of CXCR4 mRNA
      by NO was still observed in conditions in which initiation of translation was
      inhibited, suggesting that the NO effect must be mediated by a pre-existing
      protein. CXCR4 mRNA induction did not involve cGMP (guanosine 3', 5'-cyclic
      monophosphate) generation but was most likely mediated via oxidation of
      intracellular protein thiols. Finally, CD34(+) cells pretreated with NO donors
      exhibited an increased chemotactic response. This study demonstrates that the NO
      pathway can modulate CXCR4 expression in human CD34(+) cells and suggests that NO
      may play a critical role in the trafficking of hematopoietic progenitors.

PMID- 17023511
TI  - Neurokinin-1 receptor desensitization attenuates cutaneous active vasodilatation
      in humans.
AB  - To date, the neurotransmitter(s) and pathways involved in cutaneous active
      vasodilatation are not fully understood. The purpose of this study was to
      determine the potential involvement of neurokinin-1 (NK(1)) receptors to active
      vasodilatation. Our experimental model exploited our previous findings that
      repeated microdialysis infusions of substance P desensitize the NK(1) receptors
      and that substance P-induced vasodilatation contains a substantial nitric oxide
      (NO) component. Eleven subjects were equipped with four microdialysis fibres on
      the ventral forearm. Site 1 served as a control and received a continuous
      infusion of Ringer solution. Site 2 received a continuous infusion of 10 mM L
      NAME to inhibit NO synthase. Site 3 received a 10 microm dose of substance P to
      desensitize the NK(1) receptors prior to whole-body heating. Site 4 received a 10
      microm dose of substance P combined with 10 mM L-NAME. Red blood cell (RBC) flux
      was measured via laser-Doppler flowmetry, and cutaneous vascular conductance
      (CVC) was calculated as RBC flux/mean arterial pressure and normalized to maximal
      vasodilatation via 28 mM sodium nitroprusside. Substance P was infused for 15 min
      at 4 microl min(-1) in sites 3 and 4, and skin blood flow was allowed to return
      to baseline (approximately 45-60 min). Subjects then underwent a period of whole
      body heat stress to raise oral temperature 0.8-1.0 degrees C above baseline.
      Pretreatment with substance P increased CVC to 48 +/- 2% CVC(max), which was
      significantly greater than for sites pretreated with substance P combined with L
      NAME (27 +/- 2% CVC(max); P < 0.001). During whole-body heating, CVC in control
      sites increased to 69 +/- 3% CVC(max). Sites pretreated with substance P (48 +/-
      3% CVC(max)) were significantly reduced compared to control sites (P < 0.001).
      The CVC response to whole-body heat stress in L-NAME sites was significantly
      reduced (32 +/- 3% CVC(max); P < 0.001) compared to both control sites and sites
      pretreated with substance P. The CVC response to whole-body heating was nearly
      abolished in sites pretreated with substance P combined with L-NAME (20 +/- 2%
      CVC(max)) and was significantly reduced compared to the other three sites (all P
      < 0.001). These data suggest NK(1) receptors contribute to active vasodilatation
      and that combined NK(1) receptor desensitization and NO synthase inhibition
      further diminishes active vasodilatation.

PMID- 17023513
TI  - Concise review: epigenetic mechanisms contribute to pluripotency and cell lineage
      determination of embryonic stem cells.
AB  - Epigenetic mechanisms, such as histone modifications and DNA methylation, have
      been shown to play a key role in the regulation of gene transcription. Results of
      recent studies indicate that a novel "bivalent" chromatin structure marks key
      developmental genes in embryonic stem cells (ESCs), wherein a number of
      untranscribed lineage-control genes, such as Sox1, Nkx2-2, Msx1, Irx3, and Pax3,
      are epigenetically modified with a unique combination of activating and
      repressive histone modifications that prime them for potential activation (or
      repression) upon cell lineage induction and differentiation. However, results of
      these studies also showed that a subset of lineage-control genes, such as Myf5
      and Mash1, were not marked by these histone modifications, suggesting that
      distinct epigenetic mechanisms might exist for lineage-control genes in ESCs. In
      this review article, we summarize evidence regarding possible mechanisms that
      control these unique histone modifications at lineage-control gene loci in ESCs
      and consider their possible contribution to ESC pluripotency. In addition, we
      propose a novel "histone modification pulsing" model wherein individual
      pluripotent stem cells within the inner cell mass of blastocysts undergo
      transient asynchronous histone modifications at these developmental gene loci,
      thereby conferring differential responsiveness to environmental cues and
      morphogenic gradients important for cell lineage determination. Finally, we
      consider how these rapid histone modification exchanges become progressively more
      stable as ESCs undergo differentiation and maturation into specialized cell
      lineages.

PMID- 17023514
TI  - Clonogenic endothelial progenitor cells are sensitive to oxidative stress.
AB  - Endothelial progenitor cells (EPCs) circulate in the peripheral blood and reside
      in blood vessel walls. A hierarchy of EPCs exists where progenitors can be
      discriminated based on their clonogenic potential. EPCs are exposed to oxidative
      stress during vascular injury as residents of blood vessel walls or as
      circulating cells homing to sites of neovascularization. Given the links between
      oxidative injury, endothelial cell dysfunction, and vascular disease, we tested
      whether EPCs were sensitive to oxidative stress using newly developed clonogenic
      assays. Strikingly, in contrast to previous reports, we demonstrate that the most
      proliferative EPCs (high proliferative potential-endothelial colony-forming cells
      and low proliferative potential-endothelial colony-forming cells) had decreased
      clonogenic capacity after oxidant treatment. In addition, EPCs exhibited
      increased apoptosis and diminished tube-forming ability in vitro and in vivo in
      response to oxidative stress, which was directly linked to activation of a redox
      dependent stress-induced kinase pathway. Thus, this study provides novel insights
      into the effect of oxidative stress on EPCs. Furthermore, this report outlines a
      framework for understanding how oxidative injury leads to vascular disease and
      potentially limits the efficacy of transplantation of EPCs into ischemic tissues
      enriched for reactive oxygen species and oxidized metabolites.

PMID- 17023515
TI  - Long-term culturing of undifferentiated embryonic stem cells in conditioned media
      and three-dimensional fibrous matrices without extracellular matrix coating.
AB  - ESCs have unlimited proliferation potential and capability to differentiate into
      all tissue types. They are ideal cell sources for tissue engineering and cell
      therapy, but their supplies are limited. Current in vitro ESC cultures are
      carried out in tissue flasks with the surface precoated with extracellular matrix
      (ECM) proteins. T-flask cultures also require frequent subculturing because their
      limited surface area cannot support long-term growth of ESCs. In this work, ECM
      coating and frequent subculturing required in two-dimensional (2D) cultures were
      circumvented by culturing murine ESCs in three-dimensional (3D) polyethylene
      terephthalate (PET) fibrous matrices. Also, media conditioned with STO fibroblast
      cells were used to replace leukemia inhibitory factor and to effectively maintain
      the pluripotency of murine ESCs in a long-term static culture. However, the
      lactic acid present in the conditioned medium could inhibit ESC growth and induce
      spontaneous differentiation when its concentration exceeded 1.5 g/l. In addition,
      the 3D static culture could be limited by oxygen, which was depleted in the long
      term culture when cell density in the matrix was high. However, these problems
      can be alleviated in dynamic culture with improved oxygen transfer and continuous
      media perfusion. The matrix pore size also had profound effects on ESCs. The
      smaller-pore (30-60 mum) matrix gave a higher proliferation rate and Oct-4 and
      stage specific embryonic antigen-1 expressions. Overall, the 3D culturing method
      is superior to the 2D culture method and can provide an economical way to mass
      produce undifferentiated ESCs in uncoated matrices and conditioned media.

PMID- 17023516
TI  - Selection of stem cells by using antibodies that target different CD34 epitopes
      yields different patterns of T-cell differentiation.
AB  - The objective of this study was to compare the patterns of T-cell differentiation
      from CD34(+) human stem cells selected with different classes of antibody
      targeting the CD34 molecule. We compared signal-joint T-cell receptor excision
      circle (sjTREC) production in thymocytes selected with different classes of anti
      CD34 antibody. Based on these results, we studied immune reconstitution in
      nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice using human
      stem cells selected with the same antibodies that yielded variation in the
      thymocytes. Human CD34(+) stem cells were immunomagnetically selected using the
      class II QBEnd antibody (prevalent in clinical graft engineering) and the class
      III 8G12 antibody (common in diagnostic tests). Engraftment and T-cell
      reconstitution were examined after transplantation. Thymocytes selected with the
      8G12 class III antibody have a higher TREC production than those selected with
      the QBEnd class II antibody. Of mice transplanted with cells selected using the
      8G12 antibody, 50% had sjTREC production, compared with 14% of mice transplanted
      with cells selected using the clinically common antibody QBEnd. 8G12 thymic
      progenitors are characterized by higher quality in thymic distribution and higher
      activity in T-cell differentiation. Using class III antibody targeting the CD34
      molecule resulted in increased T-cell reconstitution in the NOD/SCID mouse. Use
      of a single antibody epitope targeting the CD34 molecule may lead to loss of
      cells that might provide richer T-cell reconstitution. Use of different or
      multiple epitopes, targeting of alternate stem cell markers, or use of cell
      depletion strategies might prevent this loss.

PMID- 17023517
TI  - Implication of a retrovirus-like glycoprotein peptide in the immunopathogenesis
      of Ebola and Marburg viruses.
AB  - Ebola and Marburg viruses can cause hemorrhagic fever (HF) outbreaks with high
      mortality in primates. Whereas Marburg (MARV), Ebola Zaire (ZEBOV), and Ebola
      Sudan (SEBOV) viruses are pathogenic in humans, apes, and monkeys, Ebola Reston
      (REBOV) is pathogenic only in monkeys. Early immunosuppression may contribute to
      pathogenesis by facilitating viral replication. Lymphocyte depletion,
      intravascular apoptosis, and cytokine dysregulation are prominent in fatal cases.
      Here we functionally characterize a 17 amino acid domain in filoviral
      glycoproteins that resembles an immunosuppressive motif in retroviral envelope
      proteins. Activated human or rhesus peripheral blood mononuclear cells (PBMC)
      were exposed to inactivated ZEBOV or a panel of 17mer peptides representing all
      sequenced strains of filoviruses, then analyzed for CD4+ and CD8+ T cell
      activation, apoptosis, and cytokine expression. Exposure of human and rhesus PBMC
      to ZEBOV, SEBOV, or MARV peptides or inactivated ZEBOV resulted in decreased
      expression of activation markers on CD4 and CD8 cells; CD4 and CD8 cell apoptosis
      as early as 12 h postexposure; inhibition of CD4 and CD8 cell cycle progression;
      decreased interleukin (IL)-2, IFN-gamma, and IL12-p40 expression; and increased
      IL-10 expression. In contrast, only rhesus T cells were sensitive to REBOV
      peptides. These findings are consistent with the observation that REBOV is not
      pathogenic in humans and have implications for understanding the pathogenesis of
      filoviral HF.

PMID- 17023518
TI  - Titanium dioxide nanoparticles induce emphysema-like lung injury in mice.
AB  - Titanium dioxide nanoparticles (nanoTiO2) have been widely used as a
      photocatalyst in air and water cleaning. However, these nanoparticles inhalation
      can induce pulmonary toxicity and its mechanism is not fully understood. In this
      study we investigated the pulmonary toxicity of nanoTiO2 and its molecular
      pathogenesis. The adult male ICR mice were exposed to intratracheal single dose
      of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day,
      1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway
      analyses. NanoTiO2 can induce pulmonary emphysema, macrophages accumulation,
      extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and
      epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds
      of genes include activation of pathways involved in cell cycle, apoptosis,
      chemokines, and complement cascades. In particular, nanoTiO2 up-regulates
      placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3)
      expressions that may cause pulmonary emphysema and alveolar epithelial cell
      apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in
      vitro also resulted in up-regulations of PlGF, CXCL1, CXCL5, and CCL3. These
      results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may
      be caused by activation of PlGF and related inflammatory pathways.

PMID- 17023519
TI  - Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase
      expression and activity in human bone cells.
AB  - Vitamin D is an important regulator of mineral homeostasis and bone metabolism.
      1Alpha-hydroxylation of 25-(OH)D3 to form the bioactive vitamin D hormone,
      1alpha,25-(OH)2D3, is classically considered to take place in the kidney.
      However, 1alpha-hydroxylase has been reported at extrarenal sites. Whether bone
      is a 1alpha,25-(OH)2D3 synthesizing tissue is not univocal. The aim of this study
      was to investigate an autocrine/paracrine function for 1alpha,25-(OH)2D3 in bone.
      We show that 1alpha-hydroxylase is expressed in human osteoblasts, as well as the
      vitamin D binding protein receptors megalin and cubilin. Functional analyses
      demonstrate that after incubation with the 1alpha-hydroxylase substrate 25
      (OH)D3, the osteoblasts can produce sufficient 1alpha,25-(OH)2D3 to modulate
      osteoblast activity, resulting in induced alkaline phosphatase (ALP) activity,
      osteocalcin (OC) and CYP24 mRNA expression, and mineralization. The classical
      renal regulators of 1alpha-hydroxylase, parathyroid hormone, and ambient calcium
      do not regulate 1alpha-hydroxylase in osteoblasts. In contrast, interleukin (IL)
      1beta strongly induces 1alpha-hydroxylase. Besides the bone-forming cells, we
      demonstrate 1alpha-hydroxylase activity in the bone resorbing cells, the
      osteoclasts. This is strongly dependent on osteoclast inducer RANKL. This study
      showing expression, activity, and functionality of 1alpha-hydroxylase
      unequivocally demonstrates that vitamin D can act in an auto/paracrine manner in
      bone.

PMID- 17023520
TI  - Oncostatin M is a neuroprotective cytokine that inhibits excitotoxic injury in
      vitro and in vivo.
AB  - Oncostatin M (OsM) is a member of the interleukin (IL)-6 family of cytokines and
      is well known for its role in inflammation, cell proliferation, and
      hematopoiesis. OsM, together with its glycoprotein 130 containing receptor
      complex, is expressed and regulated in most cells of the central nervous system
      (CNS), yet the function of OsM within this compartment is poorly understood. Here
      we have investigated the effect of OsM using in vitro and in vivo models of
      excitotoxic injury. Using primary cultures of mouse cortical neurons, OsM was
      shown to reduce N-methyl-D-aspartate (NMDA) -induced neuronal death by 50% when
      added simultaneously with NMDA while pretreatment of neurons with OsM fully
      prevented NMDA toxicity indicating a profound protective effect of this cytokine.
      OsM was also shown to inhibit NMDA-mediated increase in levels of free
      intracellular calcium and to selectively reduce neuronal expression of the NR2C
      subunit of the NMDA receptor. Finally, using an in vivo model of excitotoxic
      injury, OsM significantly reduced the NMDA-induced lesion volume when coinjected
      with NMDA into the mouse striatum. Taken together, these results identify OsM as
      a powerful neuroprotective cytokine and provide a rational foundation to explore
      the therapeutic potential for OsM in diseases of the CNS.

PMID- 17023521
TI  - The psychophysical relationship between bitter taste and burning sensation:
      evidence of qualitative similarity.
AB  - Although it has long been studied as a pure sensory irritant, the ability of
      capsaicin to evoke, mask, and desensitize bitter taste suggests that burning
      sensations and bitter taste might be closely related perceptually. The current
      study investigated the psychophysical relationship between bitterness and burning
      using 2 different approaches. In Experiment 1, spatial discrimination of 4 taste
      stimuli was measured in the presence or absence of capsaicin. The subjects' task
      was to report which of 3 swabs, spaced 1 cm apart and presented to the tongue
      tip, contained a taste stimulus when 1) water was presented on the other 2 swabs
      or 2) when 10 muM capsaicin was presented on all 3 swabs. The presence of
      capsaicin did not change performance on the 3 alternative forced-choice (3-AFC)
      task for sweet, sour, and salty stimuli, while the localization error for 1.8 mM
      quinine sulfate (QSO(4)) increased significantly. In Experiment 2, the perceptual
      similarity/dissimilarity of taste stimuli and capsaicin was measured directly
      using pairs of stimuli applied to opposite sides of the tongue tip on swabs
      separated by 2 cm. Multidimensional scaling analyses showed that capsaicin fell
      nearer to QSO(4) than to any other taste stimulus. Cluster analysis corroborated
      this finding: capsaicin was closely linked with QSO(4) and the capsaicin-QSO(4)
      group was separated from the other taste stimuli. The latter result indicated
      that bitterness was more similar to burning than to the other tastes. These
      findings imply that despite being mediated by different sensory modalities,
      bitterness and burn are qualitatively similar. We speculate that this similarity
      reflects a common function of these 2 sensations as sensory signals of
      potentially harmful stimuli.

PMID- 17023522
TI  - Ontogenic loss of brown adipose tissue sensitivity to beta-adrenergic stimulation
      in the ovine.
AB  - In ruminants and other large animals, expression of uncoupling protein-1 (UCP1)
      in brown adipose tissue (BAT) is confined to the perinatal period when it plays a
      key role in nonshivering thermogenesis. This study determined whether loss of
      expression of the BAT phenotype was due to reduced response to a beta-agonist,
      isoprenaline, and expression of the peroxisome proliferator-activated receptor
      (PPAR) family [PPARalpha, PPARgamma, PPAR coactivator 1alpha (PGC-1alpha)], which
      regulates UCP1 gene expression. Perirenal adipose tissue (PAT) was sampled from
      ovine fetuses, newborn lambs, and lambs on d 1, 5, 7, and 21 of life. UCP1 mRNA
      and protein in PAT increased from d 123 of fetal life to reach a maximum at birth
      followed by a rapid decrease over the first 5 d of life. Expression of the
      coactivator, PGC-1alpha and PPAR alpha, peaked between fetal day 123 and birth,
      and then declined to undetectable levels in the first days of life. In vivo
      administration of isoprenaline was able to induce expression of UCP1, PGC-1alpha,
      and PPARalpha in BAT up to 5 d of age but thereafter was ineffective. In vitro
      addition of beta-receptor, PPARalpha, and PPARgamma agonists were unable to
      overcome the suppression of UCP1, PPARalpha, and PPARgamma expression observed in
      differentiated adipocytes prepared from 30-d-old compared with 1-d-old lambs.
      These data are consistent with a model in which postnatal loss of UCP1 expression
      and beta-adrenergic induction of the brown adipocyte phenotype is due to loss of
      expression of PGC-1alpha and PPARalpha.

PMID- 17023523
TI  - Regulation of the orphan receptor TR3 nuclear functions by c-Jun N terminal
      kinase phosphorylation.
AB  - The orphan receptor TR3 functions in the nucleus as a transcription factor to
      negatively or positively regulate gene expression. c-Jun N-terminal kinase (JNK)
      phosphorylation plays an important role in modulating the nuclear functions of
      TR3. Although TR3 is the phosphorylation target of JNK, the regulatory mechanism
      of JNK on TR3 functions remains to be elucidated. Here we showed that JNK
      activator anisomycin induced TR3 phosphorylation through JNK1 rather than p38 and
      ERK signals, which is mediated by its upstream factors MAPK kinase 4 and MAPK
      kinase 7. We also identified the exact phosphorylation site of JNK to be serine
      95 at the N terminus of TR3, around which a classical JNK phosphorylation motif
      exists. Furthermore, we demonstrated that TR3 phosphorylation by JNK coincided
      with its ubiquitination and degradation, resulting in the loss of its mitogenic
      activity. Finally, we showed that JNK-induced phosphorylation blocked the DNA
      binding property of TR3 and hence diminished its transactivation activity. Taken
      together, our findings revealed a novel cross talk between TR3 and JNK signal
      pathway and shed light on the mechanism of JNK phosphorylation-dependent
      regulation on TR3 nuclear functions.

PMID- 17023524
TI  - Brain infusion of lipopolysaccharide increases uterine growth as a function of
      estrogen replacement regimen: suppression of uterine estrogen receptor-alpha by
      constant, but not pulsed, estrogen replacement.
AB  - The effects of estrogen therapy can differ depending on the regimen of estrogen
      administration. In addition, estrogen can modulate the effects of stressors. To
      examine the interaction between these systems, we infused adult female rats with
      lipopolysaccharide (LPS) into the fourth ventricle of the brain for 6 d and
      compared the effects of constant and pulsed estrogen replacement. Constant, but
      not pulsed, estrogen treatment reduced estrogen receptor-alpha (ERalpha) protein
      by 90% in the uterus and increased heat-shock proteins 70 and 90 by 74 and 48%,
      respectively, whereas progesterone receptor levels increased in all
      ovariectomized rats receiving estrogen replacement. In contrast to the uterine
      decline in ERalpha, no changes in ERalpha were observed in the hypothalamus or
      hippocampus, and ERbeta levels were unchanged in all regions tested. Brain
      infusion of LPS did not alter these proteins but increased the number of
      activated microglia in the thalamus and reduced body weight in all rats as well
      as activated the hypothalamic-pituitary-adrenal axis in ovariectomized rats, as
      determined by elevations in circulating corticosterone and progesterone. Estrogen
      treatments did not alter these markers, and no differences were observed in
      cortical choline acetyltransferase activity or nitrotyrosine for any of the
      treatment groups. The current study found an unexpected increase in uterine
      weight in lipopolysaccharide-infused rats treated with constant, but not pulsed,
      estrogen. This report suggests that constant and pulsed regimens of estrogen
      administration produce different effects and that stress may be an important
      factor in the postmenopausal intervention with estrogen.

PMID- 17023525
TI  - Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters
      development of the fetal mouse mammary gland.
AB  - Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that
      leaches from dental materials, food and beverage containers, and other plastic
      consumer products. Effects of perinatal BPA exposure on the mouse mammary gland
      have been observed in puberty and adulthood, long after the period of exposure
      has ended. The aim of this study was to examine fetal mammary gland development
      at embryonic day (E)18 and assess changes in the tissue organization and
      histoarchitecture after exposure to an environmentally relevant dose of BPA. In
      unexposed fetuses, the relative position of the fetus with respect to its female
      and male siblings in the uterus influenced growth of the ductal tree, which was
      more developed in females placed between two males than in females placed between
      two females. Exposure of dams to 250 ng BPA per kilogram body weight per day from
      E8 to E18 significantly increased ductal area and ductal extension in exposed
      fetuses and obliterated positional differences. In the stroma, BPA exposure
      promoted maturation of the fat pad and altered the localization of collagen.
      Within the epithelium, BPA exposure led to a decrease in cell size and delayed
      lumen formation. Because mammary gland development is dependent on reciprocal
      interactions between these compartments, the advanced maturation of the fat pad
      and changes in the extracellular matrix may be responsible for the altered
      growth, cell size, and lumen formation observed in the epithelium. These results
      suggest that alterations in mammary gland phenotypes observed at puberty and
      adulthood in perinatally exposed mice have their origins in fetal development.

PMID- 17023526
TI  - Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive
      oxygen species overproduction in obese Zucker diabetic fatty rats.
AB  - Vascular endothelial dysfunction has been demonstrated in obesity, but the
      molecular basis for this link has not been clarified. We examined the role of
      free fatty acids (FFA) on vascular reactivity in the obese fa/fa Zucker diabetic
      fatty (ZDF) rat. Addition of acetylcholine produced a dose-dependent relaxation
      in aortic rings of ZDF and lean +/+ rats, but the ED(50) value was higher in ZDF
      (-6.80 +/- 0.05 vs. -7.11 +/- 0.05 log(10) mol/liter, P = 0.033). A 2-wk
      treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,
      pitavastatin (3 mg/kg/d) or a reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor, apocynin (5 mmol/liter in drinking water), improved
      the response in ZDF (ED(50), -7.16 +/- 0.03 and -7.14 +/- 0.05 log(10) mol/liter,
      P = 0.008 and P = 0.015 vs. vehicle, respectively). Vasodilator response to
      sodium nitroprusside was identical between ZDF and +/+ rats. Vascular reactive
      oxygen species (ROS) levels and NADPH oxidase activity in aorta were increased in
      ZDF rats but were decreased by pitavastatin. In in vitro cell culture,
      intracellular ROS signal and NADPH oxidase subunit mRNA were increased by
      palmitate, but this palmitate-induced ROS production was inhibited by NADPH
      oxidase inhibitor or pitavastatin. In conclusion, FFA-induced NADPH oxidase
      subunit overexpression and ROS production could be involved in the endothelial
      dysfunction seen in obese ZDF rats, and this could be protected by pitavastatin
      or NADPH oxidase inhibitors.

PMID- 17023527
TI  - Altered hypothalamic leptin, insulin, and melanocortin binding associated with
      moderate-fat diet and predisposition to obesity.
AB  - Rats with a genetic predisposition to develop diet-induced obesity (DIO) have a
      preexisting reduction in central leptin and insulin sensitivity. High-fat diets
      also reduce sensitivity to leptin, insulin, and melanocortin agonists. We
      postulated that such reduced sensitivities would be associated with decreased
      binding to the hypothalamic leptin, insulin, and melanocortin receptors in
      selectively bred DIO rats and in rats fed a high-energy (HE; 31% fat) diet for 7
      wk. On HE diet, DIO rats gained 15% more weight and had 121% heavier fat pads and
      70% higher leptin levels than low fat chow-fed DIO rats. Diet-resistant (DR) rats
      gained no more weight on HE diet but had 48% heavier fat pads and 70% higher
      leptin levels than chow-fed DR rats. Compared with DR rats, DIO (125)I-leptin
      binding was 41, 36, and 40% lower in the hypothalamic dorsomedial, arcuate, and
      dorsomedial portion of the ventromedial nuclei, respectively, and arcuate (125)I
      insulin binding was 31% lower independent of diet. In contrast, hypothalamic
      melanocortin binding did not differ between DIO and DR rats. However, HE diet
      intake lowered lateral hypothalamic melanocortin-3 and melanocortin-4 receptor
      and hippocampal insulin binding of both DIO and DR rats and hypothalamic
      paraventricular nucleus melanocortin-4 receptor binding only in DR rats. Neither
      genotype nor diet affected substantia nigra or ventral tegmental area binding.
      These results corroborate our previous findings demonstrating a preexisting
      decrease in DIO hypothalamic leptin and insulin signaling and demonstrate that HE
      diet intake reduces hypothalamic melanocortin and hippocampal insulin binding.

PMID- 17023528
TI  - Estrogen modulation of MgATPase activity of nonmuscle myosin-II-B filaments.
AB  - The study tested the hypothesis that estrogen controls epithelial paracellular
      resistance through modulation of myosin. The objective was to understand how
      estrogen modulates nonmuscle myosin-II-B (NMM-II-B), the main component of the
      cortical actomyosin in human epithelial cervical cells. Experiments used human
      cervical epithelial cells CaSki as a model, and end points were NMM-II-B
      phosphorylation, filamentation, and MgATPase activity. The results were as
      follows: 1) treatment with estrogen increased phosphorylation and MgATPase
      activity and decreased NMM-II-B filamentation; 2) estrogen effects could be
      blocked by antisense nucleotides for the estrogen receptor-alpha and by ICI
      182,780, tamoxifen, and the casein kinase-II (CK2) inhibitor, 5,6-dichloro-1-beta
      (D)-ribofuranosylbenzimidazole and attenuated by AG1478 and PD98059 (inhibitors
      of epithelial growth factor receptor and ERK/MAPK) but not staurosporine [blocker
      of protein kinase C (PKC)]; 3) treatments with the PKC activator sn-1,2
      dioctanoyl diglyceride induced biphasic effect on NMM-II-B MgATPase activity: an
      increase at 1 nm to 1 microM and a decrease in activity at more than 1 microM; 4)
      sn-1,2-dioctanoyl diglyceride also decreased NMM-II-B filamentation in a
      monophasic and saturable dose dependence (EC(50) 1-10 microM); 5) when
      coincubated directly with purified NMM-II-B filaments, both CK2 and PKC decreased
      filamentation and increased MgATPase activity; 6) assays done on disassembled NMM
      II-B filaments showed MgATPase activity in filaments obtained from estrogen
      treated cells but not estrogen-depleted cells; and 7) incubations in vitro with
      CK2, but not PKC, facilitated MgATPase activity, even in disassembled NMM-II-B
      filaments. The results suggest that estrogen, in an effect mediated by estrogen
      receptor-alpha and CK2 and involving the epithelial growth factor receptor and
      ERK/MAPK cascades, increases NMM-II-B MgATPase activity independent of NMM-II-B
      filamentation status.

PMID- 17023530
TI  - Time-dependent rescue of gene expression by androgens in the mouse proximal caput
      epididymidis-1 cell line after androgen withdrawal.
AB  - Androgens are the primary regulators of epididymal structure and functions.
      Principal cells are the major cell type of the tissue and are particularly
      sensitive to androgen removal. To distinguish the direct effects of androgens on
      this cell type, DNA microarrays were used to identify androgen-regulated genes in
      the mouse proximal caput epididymidis (PC-1) cell line. PC-1 cells display tissue
      and caput-specific gene expression. We examined changes in gene expression
      occurring 2, 4, and 6 d after androgen deprivation and 2 d after androgen
      supplementation after being deprived of androgen for 2 or 4 d. Changes in
      transcript levels were investigated for mediators of androgen action; selected
      genes were analyzed by real-time RT-PCR, and changes at the protein levels were
      examined. Four distinct patterns of gene expression were activated after androgen
      withdrawal; the vast majority of genes displayed an early or late transient
      increase in expression levels. A differential ability of rescue was seen among
      androgen-regulated genes, depending on time of androgen supplementation. Many of
      the genes that were rescued at 4 d were functionally linked by direct
      interactions and converged on IGF-I. The ability for rescue after 4 d of androgen
      deprivation was severely compromised in many genes belonging to specific
      functional gene families (cell adhesion, cell growth, apoptosis, and cell cycle)
      and may be mediated in part by changes in androgen receptor coregulator
      expression. These results provide novel insights into the mechanisms of androgen
      regulation in epididymal principal cells.

PMID- 17023529
TI  - Palmitate induced mitochondrial deoxyribonucleic acid damage and apoptosis in l6
      rat skeletal muscle cells.
AB  - A major characteristic of type 2 diabetes mellitus (T2DM) is insulin resistance
      in skeletal muscle. A growing body of evidence indicates that oxidative stress
      that results from increased production of reactive oxygen species and/or reactive
      nitrogen species leads to insulin resistance, tissue damage, and other
      complications observed in T2DM. It has been suggested that muscular free fatty
      acid accumulation might be responsible for the mitochondrial dysfunction and
      insulin resistance seen in T2DM, although the mechanisms by which increased
      levels of free fatty acid lead to insulin resistance are not well understood. To
      help resolve this situation, we report that saturated fatty acid palmitate
      stimulated the expression of inducible nitric oxide (NO) synthase and the
      production of reactive oxygen species and NO in L6 myotubes. Additionally,
      palmitate caused a significant dose-dependent increase in mitochondrial DNA
      (mtDNA) damage and a subsequent decrease in L6 myotube viability and ATP levels
      at concentrations as low as 0.5 mM. Furthermore, palmitate induced apoptosis,
      which was detected by DNA fragmentation, caspase-3 cleavage, and cytochrome c
      release. N-acetyl cysteine, a precursor compound for glutathione formation,
      aminoguanidine, an inducible NO synthase inhibitor, and 5,10,15,20-tetrakis(4
      sulphonatophenyl) porphyrinato iron (III), a peroxynitrite inhibitor, all
      prevented palmitate-induced mtDNA damage and diminished palmitate-induced
      cytotoxicity. We conclude that exposure of L6 myotubes to palmitate induced mtDNA
      damage and triggered mitochondrial dysfunction, which caused apoptosis.
      Additionally, our findings indicate that palmitate-induced mtDNA damage and
      cytotoxicity in skeletal muscle cells were caused by overproduction of
      peroxynitrite.

PMID- 17023531
TI  - Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and
      cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells:
      interactions with glucose and glucocorticoids.
AB  - Lactogenic hormones stimulate food intake in rodents, ungulates, and birds. To
      test the hypothesis that lactogens regulate expression of neuropeptides that
      control appetite, we used the prolactin (PRL)-responsive rat insulinoma (INS-1)
      cell line as an experimental paradigm. INS-1 cells express mRNA for neuropeptide
      Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) but little or no
      agouti-related peptide or proopiomelanocortin. As in the hypothalamus in vivo,
      the levels of NPY mRNA in INS-1 cells were increased by glucose deprivation.
      Conversely, high media glucose concentrations (11 mm) reduced the levels of NPY
      mRNA and increased levels of CART mRNA. Rat PRL stimulated a 4- to 7-fold
      increase in NPY mRNA in INS-1 cells (P < 0.001) and reduced by 50-80% the levels
      of CART mRNA (P < 0.001). The effects of PRL on NPY mRNA were time and dose
      dependent and potentiated by glucose deprivation or exogenous dexamethasone
      (Dex). Hormonal induction of NPY mRNA was accompanied by increased secretion of
      NPY peptide into cellular conditioned media. PRL stimulated a 1.8- to 3.5-fold
      increase in expression of AMP-activated protein kinase (AMPK), which mediates in
      part the effects of hypoglycemia on NPY expression in the hypothalamus in vivo.
      Pharmacological inhibition of AMPK activity blunted slightly the effects of PRL
      on NPY and CART but reversed entirely the effects of Dex or of PRL plus Dex on
      CART mRNA. The effects of PRL on NPY, CART, and AMPK mRNA were mirrored by those
      of other lactogens and somatogens including placental lactogen and GH. Rat PRL
      and rat GH in combination had no additive or synergistic effects, suggesting that
      lactogenic and somatogenic hormones regulate neuropeptide gene expression through
      similar mechanisms. We conclude that lactogens act in concert with glucose
      deprivation and glucocorticoids to induce NPY expression and inhibit CART. We
      speculate that the lactogens facilitate food intake in response to fasting or
      nutrient deprivation, when glucose levels decline and cortisol levels rise.

PMID- 17023532
TI  - Insulin-like growth factor-I is an important antiapoptotic factor for rat leydig
      cells during postnatal development.
AB  - The present investigation examines the influence of IGF-I and the role of IGF-I
      receptor (IGF-IR) in the apoptosis/survival of Leydig cells. Immunohistochemical
      analysis of the rat testis at different ages revealed that the level of the
      phosphorylated IGF-IR increases from birth to d 20 of postnatal life, remaining
      high in the adult testis. Western blotting revealed that this level is higher in
      Leydig cells isolated from 40-d-old than from 10- or 60-d-old rats. Application
      of the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling assay revealed that IGF-I decreases the level of
      apoptosis in Leydig cells at all stages of development, and the selective
      inhibitor of IGF-IR, picropodophyllin, blocks this antiapoptotic effect. The
      mechanism underlying the antiapoptotic action of IGF-I involves the
      phosphatidylinositol 3-kinase/Akt pathway, and in immature Leydig cells, this
      growth factor enhances the expression of Bcl-2 and cellular inhibitor of
      apoptosis proteins 2, while preventing activation of caspase-3 by cleavage.
      Furthermore, IGF-II and high concentrations of insulin also evoke phosphorylation
      of IGF-IR and, like IGF-I, enhance the expression of the steroidogenic acute
      regulatory protein by Leydig cells. Inhibition of IGF-IR by picropodophyllin
      decreases the survival of Leydig cells, both in the presence and absence of IGF
      I, demonstrating that signaling via the IGF-IR plays an important role in Leydig
      cell survival.

PMID- 17023533
TI  - Kisspeptins are novel potent vasoconstrictors in humans, with a discrete
      localization of their receptor, G protein-coupled receptor 54, to atherosclerosis
      prone vessels.
AB  - The G protein-coupled receptor GPR54 (also designated KISS1) is activated by
      cleavage products of the KiSS1 protein, the kisspeptins (KP), to act as a
      molecular switch for puberty. Additionally, KP are potent inhibitors of tumor
      metastasis and play a role in placentation, both processes involving
      angiogenesis. Our aim was to investigate whether GPR54 and KP are expressed
      within normal and diseased human vasculature and what their functional role may
      be. RT-PCR screening of human blood vessels revealed a discrete localization of
      GPR54 mRNA in smooth muscle of vessels with the same developmental origins,
      aorta, coronary artery, and umbilical vein, a pattern confirmed by
      immunocytochemistry and radioligand binding. Novel ligand [(125)I]KP-13 exhibited
      saturable and high-affinity binding in aorta smooth muscle sections (dissociation
      constant K(D) = 0.2 +/- 0.03 nM), and using confocal microscopy, we found
      colocalization of receptor and peptide to vascular endothelial cells and to the
      atherosclerotic plaque of coronary artery. RIA detected 13.04 +/- 2.94 and 20.50
      +/- 5.00 fmol/g KP in human coronary artery and aorta, respectively. KP-10, KP
      13, and KP-54 acted as vasoconstrictors with comparable potency and efficacy in
      isolated rings of coronary artery (negative logarithm of the EC(50) and maximal
      response, respectively, as follows: KP-10, 7.89 +/- 0.24 and 33.7 +/- 17.0; KP
      13, 8.66 +/- 0.88 and 35.1 +/- 7.9; KP-54, 8.86 +/- 1.11 and 25.7 +/- 5.5) and
      umbilical vein (negative logarithm of the EC(50) and maximal response,
      respectively, as follows: KP-10, 8.44 +/- 022 and 24.3 +/- 3.7; KP-13, 8.43 +/-
      0.88 and 28.4 +/- 8.6; KP-54, 8.93 +/- 0.39 and 36.9 +/- 5.2). In conclusion, we
      have detected expression of both peptide and receptor in aorta, coronary artery,
      and umbilical vein and have shown for the first time that the KP are
      vasoconstrictors in humans, suggesting a previously undescribed role for GPR54
      and KP in the cardiovascular system.

PMID- 17023534
TI  - An orally active selective androgen receptor modulator is efficacious on bone,
      muscle, and sex function with reduced impact on prostate.
AB  - A number of conditions, including osteoporosis, frailty, and sexual dysfunction
      in both men and women have been improved using androgens. However, androgens are
      not widely used for these indications because of the side effects associated with
      these drugs. We describe an androgen receptor (AR) ligand that maintains expected
      anabolic activities with substantially diminished activity in the prostate.
      LGD2226 is a nonsteroidal, nonaromatizable, highly selective ligand for the AR,
      exhibiting virtually no affinity for the other intracellular receptors. We
      determined that AR bound to LGD2226 exhibits a unique pattern of protein-protein
      interactions compared with testosterone, fluoxymesterone (an orally available
      steroidal androgen), and other steroids, suggesting that LGD2226 alters the
      conformation of the ligand-binding domain. We demonstrated that LGD2226 is fully
      active in cell-based models of bone and muscle. LGD2226 exhibited anabolic
      activity on muscle and bone with reduced impact on prostate growth in rodent
      models. Biomechanical testing of bones from animals treated with LGD2226 showed
      strong enhancement of bone strength above sham levels. LGD2226 was also
      efficacious in a sex-behavior model in male rats measuring mounts, intromissions,
      ejaculations, and copulation efficiency. These results with an orally available,
      nonaromatizable androgen demonstrate the important role of the AR and androgens
      in mediating a number of beneficial effects in bone, muscle, and sexual function
      independent from the conversion of androgens into estrogenic ligands. Taken
      together, these results suggest that orally active, nonsteroidal selective
      androgen receptor modulators may be useful therapeutics for enhancing muscle,
      bone, and sexual function.

PMID- 17023535
TI  - Cholecystokinin directly inhibits neuronal activity of primary gonadotropin
      releasing hormone cells through cholecystokinin-1 receptor.
AB  - Pulsatile secretion of GnRH-1 regulates gonadotropin release from anterior
      pituitary and thus is essential for reproduction. The present study focused on
      the role of cholecystokinin (CCK) in the GnRH-1 system. CCK is a neuropeptide
      abundantly expressed in the brain, which is implicated in activation of female
      reproductive behaviors and release of anterior pituitary hormones. Using dual
      label immunocytochemistry coupled to confocal analysis, GnRH-1 neurons in adult
      mouse brain were found to express CCK-1 receptors (CCK-1R), and CCK fibers were
      detected contacting GnRH-1 axons. To address the function of CCK on GnRH-1
      neurons, calcium imaging was used to monitor patterns of activity of GnRH-1
      neurons maintained in an in vitro system known to retain many characteristics of
      GnRH-1 cells in vivo. Endogenous receptors for CCK (CCK-1R and CCK-2R) were
      blocked with selective antagonists. Results indicate that CCK-1R but not CCK-2R
      antagonist treatment increased the number of calcium peaks/GnRH-1 cell, mean peak
      amplitude, and percentage of GnRH-1 cells displaying high activity. The increased
      activity in GnRH-1 neurons observed after application of CCK-1R antagonist was
      blocked by coincubation with exogenous CCK. This study provides evidence that CCK
      acts directly on GnRH-1 neurons to attenuate GnRH-1 neuronal activity via CCK-1R
      activation.

PMID- 17023536
TI  - Inactivation of signal transducer and activator of transcription 3 in
      proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild
      obesity, and defects in compensatory refeeding.
AB  - Leptin is an adipocyte-derived hormone that signals body energy status to the
      brain by acting on multiple neuronal subgroups in the hypothalamus, including
      those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp).
      Signal transducer and activator of transcription 3 (Stat3) is an important
      intracellular signaling molecule activated by leptin, and previous studies have
      shown that mice carrying a mutated leptin receptor that abolished Stat3 binding
      are grossly obese. To determine the extent to which Stat3 signaling in Pomc
      neurons was responsible for these effects, we constructed Pomc-specific Stat3
      mutants using a Cre recombinase transgene driven by the Pomc promoter. We find
      that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is
      required for Pomc transcription. Pomc-specific Stat3 female mutant mice exhibit a
      2-fold increase in fat pad mass but only a slight increase in total body weight.
      Mutant mice remain responsive to leptin-induced hypophagia and are not
      hypersensitive to a high-fat diet; however, mutant mice fail to mount a normal
      compensatory refeeding response. These results demonstrate a requirement for
      Stat3 in transcriptional regulation of Pomc but indicate that this circuit is
      only one of several components that underlie the neuronal response to leptin and
      the role of Stat3 in that response.

PMID- 17023537
TI  - Ionic control of ocular growth and refractive change.
AB  - The physiological mechanisms underlying the abnormal vitreal and ocular growth
      and myopic refractive errors induced under conditions of visual form deprivation
      in many animal species, including humans, are unknown. This study demonstrates,
      using energy dispersive x-ray microanalysis, a systematic pattern of changes in
      the elemental distribution of K, Na, and Cl across the entire retina in
      experimental form deprivation myopia and in the 5 days required for refractive
      normalization after occluder removal. In our report we link the ionic environment
      associated with physiological activity of the retina under a translucent occluder
      to refractive change and describe large but reversible environmentally driven
      increases in potassium, sodium, and chloride abundances in the neural retina. Our
      results are consistent with the notion of ionically driven fluid movements as the
      vector underlying the myopic increase in ocular size. New treatments for myopia,
      which currently affects nearly half of the human population, may result.

PMID- 17023538
TI  - Predicted climate change alters the indirect effect of predators on an ecosystem
      process.
AB  - Changes in rainfall predicted to occur with global climate change will likely
      alter rates of leaf-litter decomposition through direct effects on primary
      decomposers. In a field experiment replicated at two sites, we show that altered
      rainfall may also change how cascading trophic interactions initiated by
      arthropod predators in the leaf litter indirectly influence litter decomposition.
      On the drier site there was no interaction between rainfall and the indirect
      effect of predators on decomposition. In contrast, on the moister site spiders
      accelerated the disappearance rate of deciduous leaf litter under low rainfall,
      but had no, or possibly a negative, indirect effect under high rainfall. Thus,
      changes resulting from the more intense hydrological cycle expected to occur with
      climate change will likely influence how predators indirectly affect an essential
      ecosystem process.

PMID- 17023539
TI  - Similarities between heterophilic and homophilic cadherin adhesion.
AB  - The mechanism that drives the segregation of cells into tissue-specific
      subpopulations during development is largely attributed to differences in
      intercellular adhesion. This process requires the cadherin family of calcium
      dependent glycoproteins. A widely held view is that protein-level discrimination
      between different cadherins on cell surfaces drives this sorting process. Despite
      this postulated molecular selectivity, adhesion selectivity has not been
      quantitatively verified at the protein level. In this work, molecular force
      measurements and bead aggregation assays tested whether differences in cadherin
      bond strengths could account for cell sorting in vivo and in vitro. Studies were
      conducted with chicken N-cadherin, canine E-cadherin, and Xenopus C-cadherin.
      Both qualitative bead aggregation and quantitative force measurements show that
      the cadherins cross-react. Furthermore, heterophilic adhesion is not
      substantially weaker than homophilic adhesion, and the measured differences in
      adhesion do not correlate with cell sorting behavior. These results suggest that
      the basis for cell segregation during morphogenesis does not map exclusively to
      protein-level differences in cadherin adhesion.

PMID- 17023540
TI  - Recent progress in understanding hydrophobic interactions.
AB  - We present here a brief review of direct force measurements between hydrophobic
      surfaces in aqueous solutions. For almost 70 years, researchers have attempted to
      understand the hydrophobic effect (the low solubility of hydrophobic solutes in
      water) and the hydrophobic interaction or force (the unusually strong attraction
      of hydrophobic surfaces and groups in water). After many years of research into
      how hydrophobic interactions affect the thermodynamic properties of processes
      such as micelle formation (self-assembly) and protein folding, the results of
      direct force measurements between macroscopic surfaces began to appear in the
      1980s. Reported ranges of the attraction between variously prepared hydrophobic
      surfaces in water grew from the initially reported value of 80-100 Angstrom to
      values as large as 3,000 Angstrom. Recent improved surface preparation techniques
      and the combination of surface force apparatus measurements with atomic force
      microscopy imaging have made it possible to explain the long-range part of this
      interaction (at separations >200 Angstrom) that is observed between certain
      surfaces. We tentatively conclude that only the short-range part of the
      attraction (<100 Angstrom) represents the true hydrophobic interaction, although
      a quantitative explanation for this interaction will require additional research.
      Although our force-measuring technique did not allow collection of reliable data
      at separations <10 Angstrom, it is clear that some stronger force must act in
      this regime if the measured interaction energy curve is to extrapolate to the
      measured adhesion energy as the surface separation approaches zero (i.e., as the
      surfaces come into molecular contact).

PMID- 17023541
TI  - The plasma membrane Na+/H+ antiporter SOS1 interacts with RCD1 and functions in
      oxidative stress tolerance in Arabidopsis.
AB  - The adverse effects of high salt on plants include Na(+) toxicity and
      hyperosmotic and oxidative stresses. The plasma membrane-localized Na(+)/H(+)
      antiporter SOS1 functions in the extrusion of toxic Na(+) from cells and is
      essential for plant salt tolerance. We report here that, under salt or oxidative
      stress, SOS1 interacts through its predicted cytoplasmic tail with RCD1, a
      regulator of oxidative-stress responses. Without stress treatment, RCD1 is
      localized in the nucleus. Under high salt or oxidative stress, RCD1 is found not
      only in the nucleus but also in the cytoplasm. Like rcd1 mutants, sos1 mutant
      plants show an altered sensitivity to oxidative stresses. The rcd1mutation causes
      a decrease in salt tolerance and enhances the salt-stress sensitivity of sos1
      mutant plants. Several genes related to oxidative-stress tolerance were found to
      be regulated by both RCD1 and SOS1. These results reveal a previously
      uncharacterized function of a plasma membrane Na(+)/H(+) antiporter in oxidative
      stress tolerance and shed light on the cross-talk between the ion-homeostasis and
      oxidative-stress detoxification pathways involved in plant salt tolerance.

PMID- 17023542
TI  - Gastric stimulation in obese subjects activates the hippocampus and other regions
      involved in brain reward circuitry.
AB  - The neurobiological mechanisms underlying overeating in obesity are not
      understood. Here, we assessed the neurobiological responses to an Implantable
      Gastric Stimulator (IGS), which induces stomach expansion via electrical
      stimulation of the vagus nerve to identify the brain circuits responsible for its
      effects in decreasing food intake. Brain metabolism was measured with positron
      emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects
      who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice
      during activation (on) and during deactivation (off) of the IGS. The Three-Factor
      Eating Questionnaire was obtained to measure the behavioral components of eating
      (cognitive restraint, uncontrolled eating, and emotional eating). The largest
      difference was in the right hippocampus, where metabolism was 18% higher (P <
      0.01) during the "on" than "off" condition, and these changes were associated
      with scores on "emotional eating," which was lower during the on than off
      condition and with "uncontrolled eating," which did not differ between
      conditions. Metabolism also was significantly higher in right anterior
      cerebellum, orbitofrontal cortex, and striatum during the on condition. These
      findings corroborate the role of the vagus nerve in regulating hippocampal
      activity and the importance of the hippocampus in modulating eating behaviors
      linked to emotional eating and lack of control. IGS-induced activation of regions
      previously shown to be involved in drug craving in addicted subjects
      (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that
      similar brain circuits underlie the enhanced motivational drive for food and
      drugs seen in obese and drug-addicted subjects, respectively.

PMID- 17023543
TI  - Mapping protein dynamics in catalytic intermediates of the redox-driven proton
      pump cytochrome c oxidase.
AB  - Redox-driven proton pumps such as cytochrome c oxidase (CcO) are fundamental
      elements of the energy transduction machinery in biological systems. CcO is an
      integral membrane protein that acts as the terminal electron acceptor in
      respiratory chains of aerobic organisms, catalyzing the four-electron reduction
      of O2 to H2O. This reduction also requires four protons taken from the cytosolic
      or negative side of the membrane, with an additional uptake of four protons that
      are pumped across the membrane. Therefore, the proton pump must embody a "gate,"
      which provides alternating access of protons to one or the other side of the
      membrane but never both sides simultaneously. However, the exact mechanism of
      proton translocation through CcO remains unknown at the molecular level.
      Understanding pump function requires knowledge of the nature and location of
      these structural changes that is often difficult to access with crystallography
      or NMR spectroscopy. In this paper, we demonstrate, with amide hydrogen/deuterium
      exchange MS, that transitions between catalytic intermediates in CcO are
      orchestrated with opening and closing of specific proton pathways, providing an
      alternating access for protons to the two sides of the membrane. An analysis of
      these results in the framework of the 3D structure of CcO indicate the spatial
      location of a gate, which controls the unidirectional proton flux through the
      enzyme and points to a mechanism by which CcO energetically couples electron
      transfer to proton translocation.

PMID- 17023544
TI  - Prostate-specific antigen values in diabetic and nondiabetic US men, 2001-2002.
AB  - Recent studies have shown that diabetic men have a lower risk of prostate cancer
      and that this association may be related to time since diagnosis. The authors
      examined the association between diabetes and prostate-specific antigen (PSA)
      levels, controlling for potential confounders, in a nationally representative
      cross-sectional survey of the US population (National Health and Nutrition
      Examination Survey 2001-2002). Diabetes classification was self-reported, and
      undiagnosed diabetes was determined with fasting plasma glucose measurements.
      Controlling for age, men with self-reported diabetes had a 21.6% lower geometric
      mean PSA level than men without diabetes. The difference increased with years
      since diagnosis (>10 years: 27.5% lower geometric mean PSA level). Overweight men
      who had had diabetes for more than 10 years had a predicted geometric mean PSA
      level 40.8% lower than that of nondiabetic, normal-weight men. These results are
      consistent with the hypothesis that long-term diabetes is associated with a lower
      risk of prostate cancer. The mechanism of this association may involve the
      regulation of PSA by androgens, although the authors are unable to confirm this
      assertion. Better understanding of the determinants of PSA level is needed to
      make the distinction between factors affecting the PSA test's accuracy and those
      altering the risk of prostate cancer.

PMID- 17023545
TI  - A prospective study of serum DDT and progesterone and estrogen levels across the
      menstrual cycle in nulliparous women of reproductive age.
AB  - The authors explored whether exposure to 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane (DDT) and its isomers and metabolites affects female
      reproductive hormones characterized by urinary pregnanediol-3-glucuronide (PdG)
      and estrone conjugate (E(1)C) levels. During 1996-1998, 287 newly married Chinese
      women nonsmokers intending to conceive were prospectively studied. Serum for DDT
      measurement was collected at enrollment, and daily menstrual diaries and urine
      specimens were collected for 1 year or until a clinical pregnancy was achieved.
      More than 500 menstrual cycles were studied totaling over 8,000 days. Day of
      ovulation was determined for each cycle, and the association of serum DDT levels
      with daily PdG and E(1)C levels in a +/-10-day window around ovulation was
      analyzed. After adjustment for covariates including age, body mass index, and
      occupational exposures, consistent inverse associations of most DDT forms
      occurred with urine E(1)C during the periovulation phase and with urine PdG
      during the luteal phase of the menstrual cycle. For example, a 10-ng/g increase
      in serum p,p'-DDE was associated with a 0.05-log(E(1)C) decrease (p = 0.03) in
      the periovulation phase and a 0.06-log(PdG) decrease (p = 0.03) in the luteal
      phase. These results support the potential for DDT to be associated with
      decrements in estrogen and progesterone levels at times during the menstrual
      cycle that are critical for ovulation and early pregnancy maintenance.

PMID- 17023546
TI  - Characterization of the human intestinal CD98 promoter and its regulation by
      interferon-gamma.
AB  - Growing evidence that epithelial CD98 plays an important role in intestinal
      inflammation focused our interest to investigate the transcriptional regulation
      of CD98. Our mouse-based in vivo and in vitro experiments revealed that
      epithelial colonic CD98 mRNA expression was transcriptionally increased in
      intestinal inflammation. We then isolated and characterized a 5'-flanking
      fragment containing the promoter region required for CD98 gene transcription.
      Primer extension and rapid amplification of 5'-cDNA ends were used to map a
      transcriptional initiation site 129 bp upstream from the translational start
      codon (ATG). Direct sequencing of the 5'-flanking region revealed the presence of
      four GC-rich stimulating protein (Sp)1 binding domains, one NF-kappaB binding
      domain, and no TATA box. Binding of Sp1 [Sp1(-874), SP1(-386), Sp1(-187), and
      Sp1(-177)] and NF-kappaB [NF-kappaB(-213)] to the promoter was confirmed by EMSA
      and supershift assays. Furthermore, chromatin immunoprecipitation experiments
      showed the in vivo DNA-Sp1 and DNA-NF-kappaB interactions under basal and IFN
      gamma-stimulated conditions. Reporter genes driven by serially truncated and site
      mutated CD98 promoters were used to examine basal and IFN-gamma-responsive
      transcription in transiently transfected Caco2-BBE cells. Our results revealed
      that Sp1(-187), Sp1(-177), and the NF-kappaB binding site were essential for
      basal and IFN-gamma-stimulated CD98 promoter activities, whereas Sp1(-874) and
      Sp1(-386) were not. The results from additional site-mutated CD98 promoters
      suggested that Sp1(-187), Sp1(-177), and the NF-kappaB site may cooperate in
      mediating basal and IFN-gamma-stimulated CD98 promoter activities. Finally, we
      demonstrated that a reduction of Sp1 or NF-kappaB expression reduced CD98 protein
      expression in unstimulated and IFN-gamma-stimulated Caco2-BBE cells.
      Collectively, these findings indicate that the Sp1 and NF-kappaB transcription
      factors are likely to play a significant role in IFN-gamma-mediated
      transcriptional regulation of CD98 in the intestinal epithelium, providing new
      insights into the regulation of CD98 expression in intestinal inflammation.

PMID- 17023547
TI  - Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia
      reperfusion injury in rats.
AB  - CXC chemokines, including human interleukin-8 and rat cytokine-induced neutrophil
      chemoattractant-1, play a crucial role in the pathogenesis of intestinal
      inflammation induced by ischemia-reperfusion (I-R). Thrombin and its specific
      receptor, protease-activated receptor 1 (PAR1), act as important players in
      inflammation. However, the association between thrombin activation and chemokine
      production during I-R has not been well studied. We investigated whether thrombin
      and PAR1 might be involved in the pathophysiology of intestinal I-R, using an in
      vivo model. Intestinal damage was induced by clamping the superior mesenteric
      artery for 30 min followed by reperfusion in male Wistar rats. Thrombin
      antithrombin complex was measured as an indicator of thrombin activation. PAR1
      expression in the intestine was evaluated by real-time PCR. The severity of the
      intestinal mucosal injury was evaluated on the distal segment of the ileum by
      several biochemical markers and histological findings. Reperfusion significantly
      increased the serum levels of thrombin-antithrombin complex and enhanced PAR1
      expression in the intestinal mucosa. The levels of both intraluminal hemoglobin
      and protein were significantly increased in the I-R group. The mucosal
      myeloperoxidase activity and expressions and/or productions of cytokine-induced
      neutrophil chemoattractant-1 and TNF-alpha were significantly increased after I
      R. These increases were inhibited by the treatment of rat with antithrombin
      intravenously before I-R at a dose of 30 U/kg. These results suggest that the
      thrombin/PAR1 pathway plays an important role in the production of these
      cytokines during I-R and that antithrombin exerts potent anti-inflammatory
      effects on this injury via inhibition of proinflammatory cytokines.

PMID- 17023548
TI  - Activation of neural circuitry and Ca2+ waves in longitudinal and circular muscle
      during CMMCs and the consequences of rectal aganglionosis in mice.
AB  - In mammals that develop rectal aganglionosis, the aganglionic segment still
      exhibits spontaneous phasic contractions that contribute to dysmotility and
      pseudoobstruction in this region. However, almost nothing is known about the
      mechanisms that generate these myogenic contractions or the effects of
      aganglionosis on the generation of Ca(2+) waves that underlie contractions of the
      longitudinal muscle (LM) and circular muscle (CM). In a mouse model of
      Hirschsprung's disease [endothelin type B receptor-deficient (Ednrb(s-l)/Ednrb(s
      l)) mice], the Ca(2+) indicator fluo-4 was used to simultaneously monitor the
      temporal activation and spread of intercellular Ca(2+) waves in the LM and CM
      during spontaneous colonic motor activities. During the intervals between colonic
      migrating motor complexes (CMMCs) in control mice, Ca(2+) waves discharged
      asynchronously between the LM and CM. However, in these same mice, during CMMCs,
      a burst of discreet Ca(2+) waves fired simultaneously in both muscle layers,
      where the propagation velocity of Ca(2+) waves significantly increased, as did
      the rate of initiation and number of collisions between Ca(2+) waves.
      Hexamethonium (300 microM) or atropine (1 microM) prevented synchronized firing
      of Ca(2+) waves. In the aganglionic distal colon of Ednrb(s-l)/Ednrb(s-l) mice,
      not only were CMMCs absent, but Ca(2+) waves between the two muscle layers fired
      asynchronously, despite increased propagation velocity. The generation of CMMCs
      in control mice involves synchronized firing of enteric motor nerves to both the
      LM and CM, explaining the synchronized firing of discreet Ca(2+) waves between
      the two muscle layers. Aganglionosis results in a sporadic and sustained
      asynchrony in Ca(2+) wave firing between the LM and CM and an absence of CMMCs.

PMID- 17023549
TI  - Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation.
AB  - Swallow and esophageal distension-induced relaxations of the lower esophageal
      sphincter (LES) are associated with an orad movement of the LES because of a
      concurrent esophageal longitudinal muscle contraction. We hypothesized that the
      esophageal longitudinal muscle contraction induces a cranially directed
      mechanical stretch on the LES and therefore studied the effects of a mechanical
      stretch on the LES pressure. In adult opossums, a silicon tube was placed via
      mouth into the esophagus and laparotomy was performed. Two needles with silk
      sutures were passed, 90 degrees apart, through the esophageal walls and silicon
      tube, 2 cm above the LES. The tube was withdrawn, and one end of each of the four
      sutures was anchored to the esophageal wall and the other end exited through the
      mouth to exert graded cranially directed stretch on the LES by using pulley and
      weights. A cranially directed stretch caused LES relaxation, and with the
      cessation of stretch there was recovery of the LES pressure. The degree an d
      duration of LES relaxation increased with the weight and the duration of stretch,
      respectively. The mean LES relaxation in all animals was 77.7 +/- 4.7%. The
      required weight to induce maximal LES relaxation differed in animals (714 +/- 348
      g). N(G)-nitro-L-arginine, a nitric oxide inhibitor, blocked the axial stretch
      induced LES relaxation almost completely (from 78 to 19%). Our data support the
      presence of an axial stretch-activated inhibitory mechanism in the LES. The role
      of axial stretch in the LES relaxation induced by swallow and esophageal
      distension requires further investigation.

PMID- 17023550
TI  - Stimulation of adenosine A1 and A2A receptors by AMP in the submucosal plexus of
      guinea pig small intestine.
AB  - Actions of adenosine 5'-monophosphate (AMP) on electrical and synaptic behavior
      of submucosal neurons in guinea pig small intestine were studied with "sharp"
      intracellular microelectrodes. Application of AMP (0.3-100 microM) evoked slowly
      activating depolarizing responses associated with increased excitability in 80.5%
      of the neurons. The responses were concentration dependent with an EC(50) of 3.5
      +/- 0.5 microM. They were abolished by the adenosine A(2A) receptor antagonist ZM
      241385 but not by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid,
      trinitrophenyl-ATP, 8-cyclopentyl-1,3-dimethylxanthine, suramin, or MRS-12201220.
      The AMP-evoked responses were insensitive to AACOCF3 or ryanodine. They were
      reduced significantly by 1) U-73122, which is a phospholipase C inhibitor; 2)
      cyclopiazonic acid, which blocks the Ca(2+) pump in intraneuronal membranes; and
      3) 2-aminoethoxy-diphenylborane, which is an inositol (1,4,5)-trisphosphate
      receptor antagonist. Inhibitors of PKC or calmodulin-dependent protein kinase
      also suppressed the AMP-evoked excitatory responses. Exposure to AMP suppressed
      fast nicotinic ionotropic postsynaptic potentials, slow metabotropic excitatory
      postsynaptic potentials, and slow noradrenergic inhibitory postsynaptic
      potentials in the submucosal plexus. Inhibition of each form of synaptic
      transmission reflected action at presynaptic inhibitory adenosine A(1) receptors.
      Slow excitatory postsynaptic potentials, which were mediated by the release of
      ATP and stimulation of P2Y(1) purinergic receptors in the submucosal plexus, were
      not suppressed by AMP. The results suggest an excitatory action of AMP at
      adenosine A(2A) receptors on neuronal cell bodies and presynaptic inhibitory
      actions mediated by adenosine A(1) receptors for most forms of neurotransmission
      in the submucosal plexus, with the exception of slow excitatory purinergic
      transmission mediated by the P2Y(1) receptor subtype.

PMID- 17023551
TI  - Effects of pelvic floor muscle contraction on anal canal pressure.
AB  - The role of pelvic floor muscle contraction in the genesis of anal canal pressure
      is not clear. Recent studies have suggested that vaginal distension increases
      pelvic floor muscle contraction. We studied the effects of vaginal distension on
      anal canal pressure in 15 nullipara asymptomatic women. Anal pressure, rest, and
      squeeze were measured using station pull-through manometry techniques with no
      vaginal probe, a 10-mm vaginal probe, and a 25-mm vaginal probe in place. Rest
      and squeeze vaginal pressures were significantly higher when measured with the 25
      mm probe compared with the 10-mm probe, suggesting that vaginal distension
      enhances pelvic floor contraction. In the presence of the 25-mm vaginal probe,
      rest and squeeze anal pressures in the proximal part of the anal canal were
      significantly higher compared with no vaginal probe or the 10-mm vaginal probe.
      On the other hand, distal anal pressures were not affected by any of the vaginal
      probes. Ultrasound imaging of the pelvic floor revealed that vaginal distension
      increased the anterior-posterior length of the puborectalis muscle. Atropine at
      15 micro g/kg had no influence on the rest and squeeze anal pressures with or
      without vaginal distension. Our data suggest that pelvic floor contractions
      increase pressures in the proximal part of the anal canal, which is anatomically
      surrounded by the puborectalis muscle. We propose that pelvic floor contraction
      plays an important role in the fecal continence mechanism by increasing anal
      canal pressure.

PMID- 17023552
TI  - Liver I/R injury is improved by the arginase inhibitor, N(omega)-hydroxy-nor-L
      arginine (nor-NOHA).
AB  - Liver ischemia-reperfusion (I/R) injury is associated with profound arginine
      depletion due to arginase release from injured hepatocytes. The purpose of this
      study was to determine whether arginase inhibition with N(omega)-hydroxy-nor-l
      arginine (nor-NOHA) would increase circulating arginine levels and decrease
      hepatic damage during liver I/R injury. The effects of nor-NOHA were initially
      tested in normal animals to determine in vivo toxicity. In the second series of
      experiments, orthotopic syngeneic liver transplantation (OLT) was performed after
      18 h of cold ischemia time in Lewis rats. Animals were given nor-NOHA (100 mg/kg)
      or saline before and after graft reperfusion. In normal animals treated with nor
      NOHA, there were no histopathological changes to organs, liver enzymes, serum
      creatinine, or body weight. In the OLT model, animals treated with saline
      exhibited markedly elevated serum transaminases and circulating arginase protein
      levels. Nor-NOHA administration blunted the increase in serum arginase activity
      by 80% and preserved serum arginine levels at 3 h after OLT. Nor-NOHA treatment
      reduced post-OLT serum liver enzyme release by 50%. Liver histology (degree of
      necrosis) in nor-NOHA-treated animals was markedly improved compared with the
      saline-treated group. Furthermore, use of the arginase inhibitor nor-NOHA did not
      influence polyamine synthesis owing to the decrease in ornithine levels. Arginase
      blockade represents a potentially novel strategy to combat hepatic I/R injury
      associated with liver transplantation.

PMID- 17023553
TI  - Estrogen and isoflavone attenuate stress-induced gastric mucosal injury by
      inhibiting decreases in gastric tissue levels of CGRP in ovariectomized rats.
AB  - We have previously reported that CGRP plays a critical role in the reduction of
      stress-induced gastric mucosal injury by increasing gastric prostacyclin (PGI(2))
      levels in rats. Estrogen has been shown to increase the production of CGRP in
      sensory neurons. Isoflavone has estrogen-like effects and is referred to as a
      phytoestrogen. Thus, we hypothesized that estrogen and isoflavone might inhibit
      ovariectomy (OVX)-induced decreases in gastric tissue levels of CGRP, thereby
      attenuating gastric mucosal injury. We examined these possibilities in the
      present study. The administration of estradiol and isoflavone for 4 wk completely
      reversed OVX-induced decreases in CGRP mRNA levels of dorsal root ganglion
      neurons (DRGs) in rats. OVX-induced decreases in gastric tissue levels of CGRP
      and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in rats were reversed by
      estradiol and isoflavone. Water-immersion restraint stress (WIR)-induced
      increases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were inhibited
      in ovariectomized rats. This inhibition was completely reversed by estradiol and
      was partially, but significantly, reversed by isoflavone. WIR-induced gastric
      mucosal injury was exacerbated by OVX, which was reversed by estradiol and
      isofolavone. In vitro experiments using DRGs isolated from rats demonstrated that
      neither estradiol nor isoflavone enhanced CGRP release from DRGs, but the former
      enhanced it in the presence of anandamide, an endogenous agonist for vanilloid
      receptor-1. These observations suggest that estrogen and isoflavone might inhibit
      OVX-induced decreases in CGRP levels in DRGs by promoting transcription, thereby
      contributing to the attenuation of stress-induced gastric mucosal injury in OVX
      rats.

PMID- 17023554
TI  - Increased intestinal permeability in obese mice: new evidence in the pathogenesis
      of nonalcoholic steatohepatitis.
AB  - A small percentage of pathologically obese subjects with fatty livers develop
      histological signs of necroinflammation and fibrosis, suggesting a variety of
      cofactors in the pathogenesis of obesity-related liver diseases including
      nonalcoholic steatohepatitis. Since several observations have linked bacterial
      endotoxins to liver damage, the aim of this study was to determine the effect of
      obesity on intestinal mucosal integrity and portal blood endotoxemia in two
      strains of obese mice: leptin-deficient (ob/ob) and hyperleptinemic (db/db) mice.
      Murine intestinal mucosal barrier function was assessed using a Ussing chamber,
      whereas ileum tight junction proteins were analyzed by immunocytochemistry and
      Western blot analysis. Circulating proinflammatory cytokines and portal blood
      endotoxin levels were measured by ELISA and the limulus test, respectively. The
      inflammatory and fibrogenic phenotype of murine hepatic stellate cells (HSCs) was
      determined by ELISA and quantitative RT-PCR. Ob/ob and db/db mice showed lower
      intestinal resistance, profoundly modified distribution of occludin and zonula
      occludens-1 in the intestinal mucosa, and higher circulating levels of
      inflammatory cytokines and portal endotoxemia compared with lean control mice.
      Moreover, HSCs isolated from ob/ob and db/db mice showed higher membrane CD14
      mRNA levels and more pronounced lipopolysaccharide-induced proinflammatory and
      fibrogenic responses than HSCs from lean animals. In conclusion, genetically
      obese mice display enhanced intestinal permeability leading to increased portal
      endotoxemia that makes HSCs more sensitive to bacterial endotoxins. We suggest
      that in metabolic syndrome, patients may likewise have a greater intestinal
      mucosa permeability and increased lipopolysaccharide levels in portal blood that
      can contribute to the liver inflammatory damage.

PMID- 17023556
TI  - TLR7/8 agonists impair monocyte-derived dendritic cell differentiation and
      maturation.
AB  - Pathogen recognition by TLR activates the innate immune response and is typically
      followed by the development of an adaptive immune response initiated by antigen
      presentation. Dendritic cells (DC) are the most efficient APC and express diverse
      TLRs, including TLR7 and -8, which have been recently identified as targets for
      ssRNA recognition during viral infection. We have studied the effect of TLR7/8
      agonists on DC differentiation and maturation from human monocytes. The synthetic
      agonist Resiquimod (R-848) or the physiological agonist ssRNA impaired monocyte
      differentiation to DC phenotypically and functionally. Induced expression of the
      nonclassical MHC molecules of the CD1 family in DC was inhibited at the protein
      and mRNA levels, and antigen acquisition was inhibited. Proinflammatory cytokine
      (including IL-6, IL-8, TNF-alpha, IL-1beta) and IL-10 production were induced
      during DC differentiation. Cross-talk between TLR4 and TLR7/8 was revealed as
      immature DC, which had been differentiated in the presence of R-848 were
      insensitive to LPS-mediated maturation and cytokine production but still induced
      allostimulation. These data lead us to suggest that ongoing viral activation of
      TLR7/8 could alter the adaptive immune response by modifying DC differentiation
      and by down-regulating DC responsiveness to a subsequent bacterial TLR4-mediated
      signal.

PMID- 17023555
TI  - Functional connectivity of frontal cortex in healthy and ADHD children reflected
      in EEG coherence.
AB  - Abnormal functional brain connectivity is a candidate factor in developmental
      brain disorders associated with cognitive dysfunction. We analyzed a substantial
      (10 min per subject) record of dense array electroencephalography with spectral
      power and coherence methods in attention-deficit hyperactivity disorder (ADHD) (n
      = 42) and control (n = 21) 10- to 13-year-old children. We found topographically
      distinct narrow band coherence differences between subject groups: ADHD subjects
      showed elevated coherence in the lower alpha (8 Hz) band and reduced coherence in
      the upper alpha (10-11 Hz) band. The 8-Hz ADHD elevation and a 2- to 6-Hz control
      group coherence elevation were independent of stimulus presentation. In response
      to visual stimulation, the ADHD group exhibited reduced evoked potential power
      and elevated frontal coherence. Only the upper alpha band control group coherence
      elevation discriminated according to ADHD group medication status. The findings
      suggest a static state of deficient connectivity in ADHD and a stimulus-induced
      state of overconnectivity within and between frontal hemispheres.

PMID- 17023557
TI  - Aspartic protease and caspase 3/7 activation are central for macrophage apoptosis
      following infection with Escherichia coli.
AB  - Macrophages are vital for host defense against microbial infections. We have
      previously shown that infection of macrophages with a nonpathogenic strain of
      Escherichia coli induces apoptosis rapidly. Here, we demonstrate that infection
      of macrophages results in the activation of caspases prior to the induction of
      the intrinsic apoptosis pathway. Caspases 9 and 3 are activated prior to the
      release of intermembrane mitochondrial protein cytochrome C into the cytosol in
      infected macrophages. Treatment with an inhibitor to caspase 9 has no effect on
      the death of macrophages and does not prevent activation of the downstream
      effector caspase 3/7. In contrast, an inhibitor to caspase 3/7 reduces cell death
      in E. coli-infected macrophages. Although caspase 9 is not required, activation
      of aspartic proteases, of which cathepsin D is one of the central members, is
      essential for activation of caspase 3/7. Treatment with pepstatin A, an inhibitor
      of aspartic proteases, markedly diminishes the activation of cathepsin D and
      caspase 3/7 and reduces death in E. coli-infected macrophages. Collectively,
      these data suggest that cathepsin D activation of caspase 3/7 may be required for
      inducing one of the death pathways elicited by E. coli.

PMID- 17023558
TI  - Differential involvement of RelB in morphine-induced modulation of chemotaxis,
      NO, and cytokine production in murine macrophages and lymphocytes.
AB  - Acute morphine impairs innate and acquired immunity. The mechanisms involved in
      immunosuppression have not been well defined yet. The transcription factor NF
      kappaB is a central regulator of immunity, and of the NF-kappaB family, RelB is
      particularly involved in the expression of genes important in immune responses.
      We investigated the involvement of RelB in morphine-induced immunosuppression in
      mice deficient for the RelB factor. RelB-/- mice and wild-type (WT) controls were
      injected s.c. with morphine 20 mg/Kg, and 1 h later, immune parameters were
      evaluated. Morphine significantly reduced macrophage production of the
      proinflammatory cytokines IL-1beta, TNF-alpha, and IL-12 in WT animals, and the
      drug failed to diminish the production of these cytokines in the RelB-/- mice. In
      contrast, the anti-inflammatory cytokine IL-10 was similarly affected in the two
      strains. Macrophage NO production was modulated by morphine in WT animals only,
      and morphine similarly decreased macrophage chemotaxis in the presence or in the
      absence of RelB. When Th1 and Th2 cytokines were evaluated, we observed a clear
      morphine-induced reduction of IL-2 and IFN-gamma production by WT splenocytes,
      whereas no effect of the drug was observed in RelB-/- mice. On the contrary, the
      production of the Th2 cytokines IL-4 and IL-10 was lessened to the same degree by
      morphine in WT and RelB-/- mice. In conclusion, our data suggest that RelB is an
      important target for morphine modulation of proinflammatory and Th1 cytokines.
      They also indicate that morphine uses multiple intracellular pathways to exert
      its generalized immunosuppression.

PMID- 17023559
TI  - S100B binding to RAGE in microglia stimulates COX-2 expression.
AB  - Besides exerting regulatory roles within astrocytes, the Ca2+-modulated protein
      of the EF-hand type S100B is released into the brain extracellular space, thereby
      affecting astrocytes, neurons, and microglia. However, extracellular effects of
      S100B vary, depending on the concentration attained and the protein being trophic
      to neurons up to nanomolar concentrations and causing neuronal apoptosis at
      micromolar concentrations. Effects of S100B on neurons are transduced by receptor
      for advanced glycation end products (RAGE). At high concentrations, S100B also up
      regulates inducible NO synthase in and stimulates NO release by microglia by
      synergizing with bacterial endotoxin and IFN-gamma, thereby participating in
      microglia activation. We show here that S100B up-regulates cyclo-oxygenase-2
      expression in microglia in a RAGE-dependent manner in the absence of cofactors
      through independent stimulation of a Cdc42-Rac1-JNK pathway and a Ras-Rac1-NF
      kappaB pathway. Thus, S100B can be viewed as an astrocytic endokine, which might
      participate in the inflammatory response in the course of brain insults, once
      liberated into the brain extracellular space.

PMID- 17023560
TI  - Rooting the tree of life using nonubiquitous genes.
AB  - Insertion and deletion (indel)-based analyses have great potential for rooting
      the tree of life, but their use has been limited because they require ubiquitous
      sequences that have not been horizontally/laterally transferred. Very few such
      sequences exist. Here we describe and demonstrate a new algorithm that can use
      nonubiquitous sequences for rooting. This algorithm, top-down indel rooting, uses
      the traditional logical framework of indel rooting, but by considering gene gains
      and losses in addition to indel gains and losses, it is able to analyze
      incomplete data sets. The method is demonstrated using theoretical examples and
      incomplete gene sets. In particular, it is applied to the well-studied Hsp70/MreB
      indel, a sequence set thought to have been compromised by gene transfers from
      Firmicutes to archaebacteria. By sequentially assigning all observable character
      states, including gene absences, to the questionable archaebacterial Hsp70 and
      MreB sequences, we demonstrate that this gene set robustly excludes the root of
      the tree of life from the Gram-negative, double-membrane prokaryotes
      independently of the archaeal character states. There are very few ubiquitous
      paralog gene sets, and most of them contain compromised data. The ability of top
      down rooting to use incomplete and/or compromised gene sets promises to make
      rooting analyses more robust and to greatly increase the number of useful indel
      sets.

PMID- 17023561
TI  - Structure-toxicity analysis of type-2 alkenes: in vitro neurotoxicity.
AB  - Acrylamide (ACR) is a conjugated type-2 alkene that produces synaptic toxicity
      presumably by sulfhydryl adduction. The alpha,beta-unsaturated carbonyl of ACR is
      a soft electrophile and, therefore, adduction of nucleophilic thiol groups could
      occur through a conjugate (Michael) addition reaction. To address the mechanism
      of thiol adduct formation and corresponding neurotoxicological importance, we
      defined structure-toxicity relationships among a series of conjugated type-2
      alkenes (1 microM-10mM), which included acrolein and methylvinyl ketone. Results
      show that exposure of rat striatal synaptosomes to these chemicals produced
      parallel, concentration-dependent neurotoxic effects that were correlated to loss
      of free sulfhydryl groups. Although differences in relative potency were evident,
      all conjugated analogs tested were equiefficacious with respect to maximal
      neurotoxicity achieved. In contrast, nonconjugated alkene or aldehyde congeners
      did not cause synaptosomal dysfunction or sulfhydryl loss. Acrolein and other
      alpha,beta-unsaturated carbonyls are bifunctional (electrophilic reactivity at
      the C-1 and C-3 positions) and could produce in vitro neurotoxicity by forming
      protein cross-links rather than thiol monoadducts. Immunoblot analysis detected
      slower migrating, presumably derivatized, synaptosomal proteins only at very high
      acrolein concentrations (>or= 25 mM). Exposure of synaptosomes to high
      concentrations of ACR (1M), N-ethylmaleimide (10mM), and methyl vinyl ketone
      (MVK) (100mM) did not alter the gel migration of synaptosomal proteins.
      Furthermore, hydralazine (1mM), which blocks the formation of protein cross
      links, did not affect in vitro acrolein neurotoxicity. Thus, type-2-conjugated
      alkenes produced synaptosomal toxicity that was linked to a loss of thiol
      content. This is consistent with our hypothesis that the mechanism of ACR
      neurotoxicity involves formation of Michael adducts with protein sulfhydryl
      groups.

PMID- 17023562
TI  - Diarrhea in neutropenic patients: a prospective cohort study with emphasis on
      neutropenic enterocolitis.
AB  - BACKGROUND: Although diarrhea is a frequent complication in neutropenic patients,
      its true incidence, risk factors and clinical course have not been investigated
      prospectively. PATIENTS AND METHODS: The study was carried out at Hacettepe
      University Hospital for Adults and involved patients over 16 years of age.
      Patients with malignant diseases who were neutropenic on admission or who became
      neutropenic during their stay in the wards between January 2001 and February 2003
      were included. They were monitored daily until discharge, exitus, or recovery
      from neutropenia-whichever occurred earlier-to monitor the presence of diarrhea
      and other infections. RESULTS: A total of 317 neutropenic episodes in 215
      patients were followed. Diarrhea was observed in 18.6% episodes, and the
      incidence of NEC was 3.5%. The etiology in 27% episodes of diarrhea could not be
      identified. The use of anthracyclines and mitoxantrone increased the incidence of
      diarrhea. Prior use of penicillin derivatives plus beta-lactam inhibitors and N
      imidazoline derivatives was associated with decreased incidence of diarrhea.
      CONCLUSIONS: Diarrhea is a common complication in neutropenic patients. Not only
      specific conditions like NEC, but also nonspecific diseases like parasitosis may
      be the cause of diarrhea in this patient population.

PMID- 17023563
TI  - A modest proposal for another phenomenological approach to psychopathology.
AB  - In 1912, Karl Jaspers published an article entitled "The Phenomenological
      Approach to Psychopathology." This and his subsequent text, General
      Psychopathology, was to exert a profound influence on the development of
      psychiatry in general and psychiatric nosology in particular. The current
      Diagnostic and Statistical Manual of Mental Disorders and International
      Classification of Diseases both reflect, at least in part, that legacy. This
      article will argue that the descriptive psychopathology of Jaspers has been
      gradually transformed into a caricature which has substituted authority for
      enquiry and simplification for subtlety. We have been left with classificatory
      systems which impose reified categories increasingly at variance with clinical
      reality and increasingly divorced from the data generated by scientific enquiry.
      Returning to the phenomenological method, despite its contradictions, may open
      the way to clinical and research approaches which free us from the current
      straight jacket of orthodoxy which is impending our progress.

PMID- 17023564
TI  - Reproductive meristem fates in Gerbera.
AB  - Flowering plants go through several phases between regular stem growth and the
      actual production of flower parts. The stepwise conversion of vegetative into
      inflorescence and floral meristems is usually unidirectional, but under certain
      environmental or genetic conditions, meristems can revert to an earlier
      developmental identity. Vegetative meristems are typically indeterminate,
      producing organs continuously, whereas flower meristems are determinate, shutting
      down their growth after reproductive organs are initiated. Inflorescence
      meristems can show either pattern. Flower and inflorescence development have been
      investigated in Gerbera hybrida, an ornamental plant in the sunflower family,
      Asteraceae. Unlike the common model species used to study flower development,
      Gerbera inflorescences bear a fixed number of flowers, and the architecture of
      the flowers differ in that Gerbera ovaries are inferior (borne below the
      perianth). This architectural difference has been exploited to show that floral
      meristem determinacy and identity are spatially and genetically distinct in
      Gerbera, and we have shown that a single SEPALLATA-like MADS domain factor
      controls both flower and inflorescence meristem fate in the plant. Although these
      phenomena have not been directly observed in Arabidopsis, the integrative role of
      the SEPALLATA function in reproductive meristem development may be general for
      all flowering plants.

PMID- 17023565
TI  - Patterning the female side of Arabidopsis: the importance of hormones.
AB  - The study of floral organ development has been a driving force in plant
      developmental biology research for the last two decades, and there is now an
      enormous wealth of information about the genetic networks underlying the
      specification of floral organ identity and the acquisition of its final
      morphology and function. These and parallel studies on leaf morphogenesis and
      development have made evident the common evolutionary origin of all plant lateral
      organs and the recurrent use of variations in the regulatory circuits involved in
      the shaping of leaves and flowers. This review summarizes the latest progress on
      the study of the development of the gynoecium, the female reproductive organ of
      the flower, stressing the connections with the developmental programme of leaf
      morphogenesis, and highlighting the common role of hormonal cues in these
      processes.

PMID- 17023566
TI  - Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute
      mountain sickness.
AB  - Acetazolamide, a potent carbonic anhydrase (CA) inhibitor, is the most commonly
      used and best-studied agent for the amelioration of acute mountain sickness
      (AMS). The actual mechanisms by which acetazolamide reduces symptoms of AMS,
      however, remain unclear. Traditionally, acetazolamide's efficacy has been
      attributed to inhibition of CA in the kidneys, resulting in bicarbonaturia and
      metabolic acidosis. The result is offsetting hyperventilation-induced respiratory
      alkalosis and allowance of chemoreceptors to respond more fully to hypoxic
      stimuli at altitude. Studies performed on both animals and humans, however, have
      shown that this explanation is unsatisfactory and that the efficacy of
      acetazolamide in the context of AMS is likely due to a multitude of effects. This
      review summarizes the known systemic effects of acetazolamide and incorporates
      them into a model encompassing several factors that are likely to play a key role
      in the drug's efficacy. Such factors include not only metabolic acidosis
      resulting from renal CA inhibition but also improvements in ventilation from
      tissue respiratory acidosis, improvements in sleep quality from carotid body CA
      inhibition, and effects of diuresis.

PMID- 17023568
TI  - Tissue compartment-specific role of estrogen receptor subtypes in immune cell
      cytokine production following trauma-hemorrhage.
AB  - Although 17beta-estradiol administration following trauma-hemorrhage attenuates
      plasma cytokines and alteration in immune cell cytokine production, it is not
      known whether the salutary effects are mediated via estrogen receptor (ER)-alpha
      or ER-beta. Accordingly, we examined which ER subtype predominantly mediates the
      salutary effects of 17beta-estradiol on systemic inflammatory response/immune
      cell cytokine production in various tissues following trauma-hemorrhage. Male
      rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min) and
      fluid resuscitation. The ER-alpha agonist propyl pyrazole triol (PPT; 5
      microg/kg), the ER-beta agonist diarylpropionitrile (DPN; 5 microg/kg), 17beta
      estradiol (50 microg/kg), or vehicle (10% DMSO) was injected subcutaneously
      during resuscitation, and various measurements were made 24 h thereafter. 17beta
      Estradiol or PPT administration following trauma-hemorrhage prevented the
      increase in plasma IL-6 and IL-10 levels that were observed in vehicle-treated
      animals. IL-6 and TNF-alpha production by Kupffer cells increased; however,
      splenic macrophages (SMPhi), alveolar macrophages (AMPhi), and peripheral blood
      mononuclear cells (PBMC) had decreased release of these cytokines after trauma
      hemorrhage. IL-10 production, however, increased in all macrophage populations.
      Administration of 17beta-estradiol following trauma-hemorrhage prevented all of
      these alterations. PPT had the same effects as 17beta-estradiol on IL-6 and TNF
      alpha production by Kupffer cells and SMPhi, and DPN had the same effects on
      AMPhi and PBMC. The same effects as 17beta-estradiol on IL-10 production were
      observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally
      effective on SMPhi and AMPhi. Thus ER subtypes have tissue compartment-specific
      roles in mediating the effects of 17beta-estradiol on immune cell functions
      following trauma-hemorrhage.

PMID- 17023569
TI  - Effects of assuming constant optical scattering on measurements of muscle
      oxygenation by near-infrared spectroscopy during exercise.
AB  - The aim of this study was to examine the effects of assuming constant reduced
      scattering coefficient (mu'(s)) on the muscle oxygenation response to incremental
      exercise and its recovery kinetics. Fifteen subjects (age: 24 +/- 5 yr) underwent
      incremental cycling exercise. Frequency domain near-infrared spectroscopy (NIRS)
      was used to estimate deoxyhemoglobin concentration {[deoxy(Hb+Mb)]} (where Mb is
      myoglobin), oxyhemoglobin concentration {[oxy(Hb+Mb)]}, total Hb concentration
      (Total[Hb+Mb]), and tissue O(2) saturation (Sti(O(2))), incorporating both
      continuous measurements of mu'(s) and assuming constant mu'(s). When measuring
      mu'(s), we observed significant changes in NIRS variables at peak work rate
      Delta[deoxy(Hb+Mb)] (15.0 +/- 7.8 microM), Delta[oxy(Hb+Mb)] (-4.8 +/- 5.8
      microM), DeltaTotal[Hb+Mb] (10.9 +/- 8.4 microM), and DeltaSti(O(2))(-11.8 +/-
      4.1%). Assuming constant mu'(s) resulted in greater (P < 0.01 vs. measured
      mu'(s)) changes in the NIRS variables at peak work rate, where
      Delta[deoxy(Hb+Mb)] = 24.5 +/- 15.6 microM, Delta[oxy(Hb+Mb)] = -9.7 +/- 8.2
      microM, DeltaTotal[Hb+Mb] = 14.8 +/- 8.7 microM, and DeltaSti(O(2))= -18.7 +/-
      8.4%. Regarding the recovery kinetics, the large 95% confidence intervals (CI)
      for the difference between those determine measuring mu'(s) and assuming constant
      mu'(s) suggested poor agreement between methods. For the mean response time
      (MRT), which describes the overall kinetics, the 95% confidence intervals were
      MRT - [deoxy(Hb+Mb)] = 26.7 s; MRT - [oxy(Hb+Mb)] = 11.8 s, and MRT - Sti(O(2))=
      11.8 s. In conclusion, mu'(s) changed from light to peak exercise. Furthermore,
      assuming a constant mu'(s) led to an overestimation of the changes in NIRS
      variables during exercise and distortion of the recovery kinetics.

PMID- 17023570
TI  - Impact of sex and age on bone marrow immune responses in a murine model of trauma
      hemorrhage.
AB  - Although studies have demonstrated that trauma markedly alters the bone marrow
      immune responses, sex and age are crucial determinants under such conditions and
      have not been extensively examined. To study this, 21- to 27-day-old (premature),
      6- to 8-wk-old (mature), and 20- to 24-mo-old (aged) male and female (proestrus)
      C3H/HeN mice were sham operated or subjected to trauma (i.e., midline laparotomy)
      and hemorrhagic shock (30 +/- 5 mmHg for 90 min) followed by fluid resuscitation.
      Twenty-four hours after resuscitation, bone marrow cells were harvested. Trauma
      hemorrhage induced an increased number of the early pluripotent stem cell
      associated bone marrow cell subsets (Sca1(+)CD34(-)CD117(+/-)lin(+/-)) in young
      mice. The CD117(+) proportion of these cell subsets increased in mature proestrus
      females, but not in males. Aged males displayed significant lower numbers of
      Sca1(+)CD34(-)CD117(+/-)lin(+/-) cells compared with young male mice. Trauma
      hemorrhage also increased development of granulocyte/macrophage progenitor cells
      (CD11b(+)Gr-1(+)). Proliferative responses to granulocyte macrophage colony
      stimulating factor were maintained in mature and aged proestrus females, but
      decreased in young mice and mature males. Augmented differentiation into
      monocyte/macrophage lineage in mature and aged proestrus females was observed and
      associated with the maintained release of TNF-alpha and IL-6. Conversely,
      increased IL-10 and PGE(2) production was observed in the male trauma-hemorrhage
      groups. Thus, sex- and age-specific effects in bone marrow differentiation and
      immune responses after trauma-hemorrhage occur, which are likely to contribute to
      the sex- and age-related differences in the systemic immune responses under such
      conditions.

PMID- 17023571
TI  - Differential sensitivities of cerebral and brachial blood flow to hypercapnia in
      humans.
AB  - Although it is known that the vasculatures of the brain and the forearm are
      sensitive to changes in arterial Pco(2), previous investigations have not made
      direct comparisons of the sensitivities of cerebral blood flow (CBF) (middle
      cerebral artery blood velocity associated with maximum frequency of Doppler
      shift; Vp) and brachial blood flow (BBF) to hypercapnia. We compared the
      sensitivities of Vp and BBF to hypercapnia in humans. On the basis of the
      critical importance of the brain for the survival of the organism, we
      hypothesized that Vp would be more sensitive than BBF to hypercapnia. Nine
      healthy males (30.1 +/- 5.2 yr, mean +/- SD) participated. Euoxic hypercapnia
      (end-tidal Po(2) = 88 Torr, end-tidal Pco(2) = 9 Torr above resting) was achieved
      by using the technique of dynamic end-tidal forcing. Vp was measured by
      transcranial Doppler ultrasound as an index of CBF, whereas BBF was measured in
      the brachial artery by echo Doppler. Vp and BBF were measured during two 60-min
      trials of hypercapnia, each trial separated by 60 min. Since no differences in
      the responses were found between trials, data from both trials were averaged to
      make comparisons between Vp and BBF. During hypercapnia, Vp and BBF increased by
      34 +/- 8 and 14 +/- 8%, respectively. Vp remained elevated throughout the
      hypercapnic period, but BBF returned to baseline levels by 60 min. The Vp CO(2)
      sensitivity was greater than BBF (4 +/- 1 vs. 2 +/- 1%/Torr; P < 0.05). Our
      findings confirm that Vp has a greater sensitivity than BBF in response to
      hypercapnia and show an adaptive response of BBF that is not evident in Vp.

PMID- 17023572
TI  - Association of mitochondrial SOD deficiency with salt-sensitive hypertension and
      accelerated renal senescence.
AB  - Mitochondria are the major source of superoxide (O(2)(-)) in the aerobic
      organisms. O(2)(-) produced by the mitochondria is converted to hydrogen peroxide
      by mitochondrial superoxide dismutase (SOD2). Mice with complete SOD2 deficiency
      (SOD2(-/-)) exhibit dilated cardiomyopathy and fatty liver leading to neonatal
      mortality, whereas mice with partial SOD2 deficiency (SOD2(+/-)) show evidence of
      O(2)(-)-induced mitochondrial damage resembling cell senescence. Since earlier
      studies have provided compelling evidence for the role of oxidative stress and
      tubulointerstitial inflammation in the pathogenesis of hypertension, we tested
      the hypothesis that partial SOD2 deficiency may result in hypertension. Wild-type
      (SOD2(+/+)) and partial SOD2-deficient (SOD2(+/-)) mice had similar blood
      pressures at 6-7 mo of age, but at 2 yr SOD2(+/-) mice had higher blood pressure.
      Oxidative stress, renal interstitial T-cell and macrophage infiltration, tubular
      damage, and glomerular sclerosis were all significantly increased in 2-yr-old
      SOD2(+/-) mice. High-salt diet induced hypertension in 6-mo-old SOD2-deficient
      mice but not in wild-type mice. In conclusion, partial SOD2 deficiency results in
      oxidative stress and renal interstitial inflammation, changes compatible with
      accelerated renal senescence and salt-sensitive hypertension. These findings are
      consistent with the pattern described in numerous other models of salt-sensitive
      hypertension and resemble that commonly seen in elderly humans.

PMID- 17023573
TI  - A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution
      of cocaine to the brain in mice.
AB  - The predominantly human sequence, high-affinity anticocaine monoclonal antibody
      (mAb) 2E2 was cleared slowly from mouse blood by a first-order process with an
      elimination t(1/2) of 8.1 days. Infused 2E2 also produced a dramatic dose
      dependent increase in plasma cocaine concentrations and a concomitant decrease in
      the brain cocaine concentrations produced by an i.v. injection of cocaine HCl
      (0.56 mg/kg). At the highest dose of 2E2 tested (3:1, mAb/drug), cocaine was not
      detectable in the brain. Pharmacokinetic studies showed that the normal
      disappearance of cocaine from plasma was described by a two-compartment
      pharmacokinetic model with distribution t(1/2alpha) and terminal elimination
      t(1/2beta) values of 1.9 and 26.1 min, respectively. In the presence of an
      equimolar dose of mAb 2E2, there was a 26-fold increase in the area under the
      plasma cocaine concentration-time curve (AUC) relative to the AUC in the absence
      of 2E2. Consequently, 2E2 decreased the volume of distribution of cocaine from
      6.0 to 0.20 l/kg, which approximated that of 2E2 (0.28 l/kg). However, cocaine
      was still rapidly cleared from plasma, and its elimination was now described by a
      single-compartment model with an elimination t(1/2) of 17 min. Importantly, 2E2
      also produced a 4.5-fold (78%) decrease in the cocaine AUC in the brain.
      Therefore, the effect of 2E2 on plasma and brain cocaine concentrations was
      predominantly caused by a change in the distribution of cocaine with negligible
      effects on its rate of clearance. These data support the concept of immunotherapy
      for drug abuse.

PMID- 17023574
TI  - Gene-expression signature of benign monoclonal gammopathy evident in multiple
      myeloma is linked to good prognosis.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) can progress to
      multiple myeloma (MM). Although these diseases share many of the same genetic
      features, it is still unclear whether global gene-expression profiling might
      identify prior genomic signatures that distinguish them. Through significance
      analysis of microarrays, 52 genes involved in important pathways related to
      cancer were differentially expressed in the plasma cells of healthy subjects
      (normal plasma-cell [NPC]; n=22) and patients with stringently defined
      MGUS/smoldering MM (n=24) and symptomatic MM (n=351) (P<.001). Unsupervised
      hierarchical clustering of 351 patients with MM, 44 with MGUS (24+20), and 16
      with MM from MGUS created 2 major cluster branches, one containing 82% of the
      MGUS patients and the other containing 28% of the MM patients, termed MGUS-like
      MM (MGUS-L MM). Using the same clustering approach on an independent cohort of
      214 patients with MM, 27% were found to be MGUS-L. This molecular signature,
      despite its association with a lower incidence of complete remission (P=.006),
      was associated with low-risk clinical and molecular features and superior
      survival (P<.01). The MGUS-L signature was also seen in plasma cells from 15 of
      20 patients surviving more than 10 years after autotransplantation. These data
      provide insight into the molecular mechanisms of plasma-cell dyscrasias.

PMID- 17023575
TI  - Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel,
      orally available small-molecule inhibitor enzastaurin (LY317615.HCl).
AB  - In multiple myeloma (MM) protein kinase C (PKC) signaling pathways have been
      implicated in cell proliferation, survival, and migration. Here we investigated
      the novel, orally available PKC-inhibitor enzastaurin for its anti-MM activity.
      Enzastaurin specifically inhibits phorbol ester-induced activation of PKC
      isoforms, as well as phosphorylation of downstream signaling molecules MARCKS and
      PKCmu. Importantly, it also inhibits PKC activation triggered by growth factors
      and cytokines secreted by bone marrow stromal cells (BMSCs), costimulation with
      fibronectin, vascular endothelial growth factor (VEGF), or interleukin-6 (IL-6),
      as well as MM patient serum. Consequently, enzastaurin inhibits proliferation,
      survival, and migration of MM cell lines and MM cells isolated from multidrug
      resistant patients and overcomes MM-cell growth triggered by binding to BMSCs and
      endothelial cells. Importantly, strong synergistic cytotoxicity is observed when
      enzastaurin is combined with bortezomib and moderate synergistic or additive
      effects when combined with melphalan or lenalidomide. Finally, tumor growth,
      survival, and angiogenesis are abrogated by enzastaurin in an in vivo xenograft
      model of human MM. Our results therefore demonstrate in vitro and in vivo
      efficacy of the orally available PKC inhibitor enzastaurin in MM and strongly
      support its clinical evaluation, alone or in combination therapies, to improve
      outcome in patients with MM.

PMID- 17023576
TI  - A common genetic variant in XPD associates with risk of 5q- and 7q-deleted acute
      myeloid leukemia.
AB  - Numerous structural genetic abnormalities observed in acute myeloid leukemia
      (AML) illustrate the heterogeneity of this disease, which likely has contributed
      to difficulty in identifying susceptibility alleles for AML. We previously
      reported that carriers of the glutamine-encoding allele at codon 751 of the
      xeroderma pigmentosum group D (XPD) DNA repair gene were significantly more
      likely to have a karyotype associated with a less favorable prognosis, and
      hypothesized that this observation was driven by an association between the codon
      751 variant and risk of developing AML with specific structural abnormalities.
      Using a case series of 927 patients with AML, we show here that the XPD codon 751
      glutamine-encoding variant significantly associates with risk of developing AML
      with a chromosome 5q deletion (odds ratio [OR] 2.09; 95% confidence interval [CI]
      1.14-3.81; n=69; P=.02) or a chromosome 7q deletion (OR 2.27; 95% CI 1.09-4.71;
      n=47; P=.03), but not with any other commonly recurring cytogenetic lesion.

PMID- 17023577
TI  - Molecular relapse in adult standard-risk ALL patients detected by prospective MRD
      monitoring during and after maintenance treatment: data from the GMALL 06/99 and
      07/03 trials.
AB  - Although levels of minimal residual disease (MRD) decrease below the detection
      limit in most adult patients with standard-risk acute lymphoblastic leukemia
      (ALL) after consolidation treatment, about 30% of these patients will ultimately
      relapse. To evaluate the power of MRD monitoring as an indicator of impending
      relapse, we prospectively analyzed postconsolidation samples of 105 patients
      enrolled in the German Multicenter ALL (GMALL) trial by real-time quantitative
      polymerase chain reaction (PCR) of clonal immune gene rearrangements. All
      patients were in hematologic remission, had completed first-year
      polychemotherapy, and tested MRD negative prior to study entry. Twenty-eight of
      105 patients (27%) converted to MRD positivity thereafter, and 17 of 28 (61%)
      relapsed so far. Median time from molecular (MRD-positive) to clinical relapse
      was 9.5 months. In 15 of these patients, MRD within the quantitative range of PCR
      was measured in hematologic remission, and 13 of these patients (89%) relapsed
      after a median interval of 4.1 months. Of the 77 continuously MRD-negative
      patients, only 5 (6%) have relapsed. We conclude that conversion to MRD
      positivity during the early postconsolidation phase in adult standard-risk ALL
      patients is highly predictive of subsequent hematologic relapse. As a result of
      the study, as of spring 2006, salvage treatment in the ongoing GMALL trial is
      intended to be started at the time of recurrence of quantifiable MRD.

PMID- 17023578
TI  - Caveolin-1 regulates expression of junction-associated proteins in brain
      microvascular endothelial cells.
AB  - Recent evidence from this laboratory indicated that reduced expression of
      caveolin-1 accompanied the diminished expression of tight junction (TJ)
      associated proteins occludin and zonula occludens-1 (ZO-1) following stimulation
      of brain microvascular endothelial cells (BMECs) with the chemokine CCL2
      (formerly called MCP-1). Because attenuated caveolin-1 levels have also been
      correlated with heightened permeability of other endothelia, the objective of
      this study was to test the hypothesis that reduced caveolin-1 expression is
      causally linked to the action of CCL2 on BMEC junctional protein expression and
      barrier integrity. This was achieved using adenovirus to nondestructively deliver
      caveolin-1 siRNA (Ad-siCav-1) to BMEC monolayers, which model the blood-brain
      barrier (BBB). Treatment with siRNA reduced the caveolin-1 protein level as well
      as occludin and ZO-1. Additionally, occludin exhibited dissociation from the
      cytoskeletal framework. These changes were attended by comparable alterations in
      adherens junction (AJ)-associated proteins, VE-cadherin and beta-catenin,
      increased BMEC paracellular permeability, and facilitated the ability of CCL2 to
      stimulate monocytic transendothelial migration. Furthermore, treating BMECs with
      cavtratin, a synthetic cell-permeable peptide encoding the caveolin-1 scaffolding
      domain, antagonized effects of both Ad-siCav-1 and CCL2. These results
      collectively highlight caveolin-1 loss as a critical step in CCL2-induced
      modulation of BMEC junctional protein expression and integrity, and possibly
      serve a crucial role in regulating inflammation at the BBB.

PMID- 17023579
TI  - Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in
      mice.
AB  - Recent studies have shown that endothelial protein C receptor (EPCR)
      polymorphisms and soluble EPCR levels are associated with thrombotic diseases. It
      is unknown whether membrane EPCR (mEPCR) heterozygosity and/or physiologically
      elevated sEPCR levels directly impact the hemostatic balance and the outcome of
      endotoxemia. In these studies, thrombin infusion experiments revealed that EPCR
      heterozygosity (Procr+/-) impaired protein C activation by approximately 30%.
      Infusion of factor Xa with phospholipid demonstrated that the Procr+/- genotype
      increased the coagulant response relative to wild-type mice. Challenge of the
      Procr+/- mice with lipopolysaccharide (LPS) did not significantly exaggerate
      their response compared with wild-type mice. We also generated mice in which one
      allele of full-length EPCR was replaced by sEPCR (Procrs/+). Compared with
      Procr+/- mice, Procrs/+ mice had 5-fold higher sEPCR and similar mEPCR levels.
      Procr+/- and Procrs/+ mice generated similar levels of activated protein C (APC)
      upon thrombin infusion. They also exhibited a similar coagulant response upon
      factor Xa/phospholipid infusion. Only supraphysiologic levels of sEPCR could
      influence protein C activation and exaggerate the coagulant response. In
      conclusion, mEPCR, but not physiologically elevated sEPCR, regulated protein C
      activation. Procr heterozygosity results in a mild increase of thrombosis
      tendency and little influence on the response to endotoxin.

PMID- 17023581
TI  - Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F
      mutant levels in patients with essential thrombocythemia show that minor mutant
      positive clones can remain stable for many years.
AB  - Essential thrombocythemia (ET) is heterogeneous with respect to natural history,
      X-chromosome inactivation patterns (XCIPs), and presence of the V617F mutation in
      Janus kinase 2 (JAK2). We studied 111 patients with ET; 39% were JAK2 mutant
      positive, and clone size (percentage mutant JAK2) was concordant with XCIP when
      constitutive T-cell patterns were taken into account. JAK2 mutant clones were
      present in both clonal and polyclonal cases as determined by XCIP, and the former
      had higher mutant JAK2 levels (median 26% versus 16%; P=.001). No change was
      observed in serial XCIP analysis of 14 polyclonal patients over a median follow
      up of 61 months. Furthermore, 18 of 19 mutant-positive patients showed no
      significant change in mutant JAK2 level over a median follow-up of 47 months.
      These results suggest that, in many cases of ET, a small stable clone containing
      a JAK2 mutation can be maintained as a subpopulation for many years.

PMID- 17023580
TI  - L-arginine availability regulates T-lymphocyte cell-cycle progression.
AB  - L-arginine (L-Arg) plays a central role in several biologic systems including the
      regulation of T-cell function. L-Arg depletion by myeloid-derived suppressor
      cells producing arginase I is seen in patients with cancer inducing T-cell
      anergy. We studied how L-Arg starvation could regulate T-cell-cycle progression.
      Stimulated T cells cultured in the absence of L-Arg are arrested in the G0
      G1phase of the cell cycle. This was associated with an inability of T cells to up
      regulate cyclin D3 and cyclin-dependent kinase 4 (cdk4), but not cdk6, resulting
      in an impaired downstream signaling with a decreased phosphorylation of Rb
      protein and a low expression and binding of E2F1. Silencing of cyclin D3
      reproduced the cell cycle arrest caused by L-Arg starvation. The regulation of
      cyclin D3 and cdk4 by L-Arg starvation occurs at transcriptional and
      posttranscriptional levels. Signaling through GCN2 kinase is triggered during
      amino acid starvation. Experiments demonstrated that T cells from GCN2 knock-out
      mice did not show a decreased proliferation and were able to up-regulate cyclin
      D3 when cultured in the absence of L-Arg. These results contribute to the
      understanding of a central mechanism by which cancer and other diseases
      characterized by high arginase I production may cause T-cell dysfunction.

PMID- 17023582
TI  - IL-7-induced proliferation of recent thymic emigrants requires activation of the
      PI3K pathway.
AB  - The IL-7 cytokine promotes the survival of a diverse T-cell pool, thereby
      ensuring an efficient immune response. Moreover, IL-7 induces the proliferation
      of recent thymic emigrants (RTEs) in neonates. Here, we demonstrate that the
      survival and proliferative effects of IL-7 on human RTEs can be distinguished on
      the basis of dose as well as duration of IL-7 administration. A dose of 0.1 ng/mL
      IL-7 is sufficient to promote viability, whereas cell-cycle entry is observed
      only at doses higher than 1 ng/mL. Moreover, a short 1-hour exposure to high-dose
      IL-7 (10 ng/mL) induces long-term survival but continuous IL-7 exposure is
      necessary for optimal cell-cycle entry and proliferation. We find that distinct
      signaling intermediates are activated under conditions of IL-7-induced survival
      and proliferation; STAT5 tyrosine phosphorylation does not correlate with
      proliferation, whereas up-regulation of the glucose transporter Glut-1 as well as
      increased glucose uptake are markers of IL-7-induced cell cycle entry. Glut-1 is
      directly regulated by PI3K and, indeed, inhibiting PI3K activity abrogates IL-7
      induced proliferation. Our finding that the survival and proliferation of RTEs
      are differentially modulated by the dose and kinetics of exogenous IL-7 has
      important implications for the clinical use of this cytokine.

PMID- 17023583
TI  - Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle
      reticulocytes.
AB  - KCl cotransport (KCC) activity contributes to pathologic dehydration in sickle
      (SS) red blood cells (RBCs). KCC activation by urea was measured in SS and normal
      (AA) RBCs as Cl-dependent Rb influx. KCC-mediated volume reduction was assessed
      by measuring reticulocyte cellular hemoglobin concentration (CHC) cytometrically.
      Urea activated KCC fluxes in fresh RBCs to levels seen in swollen cells, although
      SS RBCs required lower urea concentrations than did normal (AA) RBCs. Little
      additional KCC stimulation by urea occurred in swollen AA or SS RBCs. The pH
      dependence of KCC in "euvolemic" SS RBCs treated with urea was similar to that in
      swollen cells. Urea triggered volume reduction in SS and AA reticulocytes,
      establishing a higher CHC. Volume reduction was Cl dependent and was limited by
      the KCC inhibitor, dihydro-indenyl-oxyalkanoic acid. Final CHC depended on urea
      concentration, but not on initial CHC. Under all activation conditions, volume
      reduction was exaggerated in SS reticulocytes and produced higher CHCs than in AA
      reticulocytes. The sulfhydryl-reducing agent, dithiothreitol, normalized the
      sensitivity of KCC activation to urea in SS RBCs and mitigated the urea
      stimulated volume decrease in SS reticulocytes, suggesting that the dysfunctional
      activity of KCC in SS RBCs was due in part to reversible sulfhydryl oxidation.

PMID- 17023584
TI  - Evidence for an immune barrier after in utero hematopoietic-cell transplantation.
AB  - The competence of the immune system of the developing fetus to act as a barrier
      to in utero hematopoietic-cell transplantation (IUHCT) has been a source of
      debate. Until now, comparisons of allogeneic and congenic engraftment have been
      inconclusive due to methodologic limitations resulting in minimal and inefficient
      engraftment. In this study, E14 fetal mice received transplants of either
      allogeneic or congenic bone marrow using a new intravascular technique that
      allows definitive administration of much higher doses of donor cells. Our results
      demonstrate that 100% of surviving recipients demonstrate engraftment at 1 week
      of age, but that 70% of allogeneic recipients lose engraftment by 1 month of age,
      and 80% ultimately fail to sustain long-term chimerism. In contrast, all congenic
      recipients maintain stable, long-term, multilineage chimerism. These results
      strongly support an immune barrier to allogeneic engraftment after IUHCT.

PMID- 17023585
TI  - Cancer-testis antigens are commonly expressed in multiple myeloma and induce
      systemic immunity following allogeneic stem cell transplantation.
AB  - Immunotherapies using cancer-testis (CT) antigens as targets represent a
      potentially useful treatment in patients with multiple myeloma (MM) who commonly
      show recurrent disease following chemotherapy. We analyzed the expression of 11
      CT antigens in bone marrow samples from patients with MM (n=55) and healthy
      donors (n=32) using reverse transcriptase-polymerase chain reaction (RT-PCR). CT
      antigens were frequently expressed in MM with 56% (MAGEC2), 55% (MAGEA3), 35%
      (SSX1), 20% (SSX4, SSX5), 16% (SSX2), 15% (BAGE), 7% (NY-ESO-1), and 6% (ADAM2,
      LIPI) expressing the given antigen. Importantly, CT antigens were not expressed
      in healthy bone marrow. Analyzing patients with MM (n=66) for antibody responses
      against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT
      antigens preferentially in patients who had received allogeneic stem cell
      transplantation (alloSCT). Antibody responses against NY-ESO-1 correlated with NY
      ESO-1-specific CD4+ and CD8+ T-cell responses against peptide NY-ESO-1(51-62) and
      CD4+ responses against NY-ESO-1(121-140) in 1 of these patients. These allogeneic
      immune responses were not detectable in pretransplantation samples and in the
      patients' stem cell donors, indicating that CT antigens might indeed represent
      natural targets for graft-versus-myeloma effects. Immune responses induced by
      alloSCT could be boosted by active CT antigen-specific immunotherapy, which might
      help to achieve long-lasting remissions in patients with MM.

PMID- 17023587
TI  - Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to
      traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface.
AB  - A key feature of Plasmodium falciparum, the parasite causing the most severe form
      of malaria in humans, is its ability to export parasite molecules onto the
      surface of the erythrocyte. The major virulence factor and variant surface
      protein PfEMP1 (P falciparum erythrocyte membrane protein 1) acts as a ligand to
      adhere to endothelial receptors avoiding splenic clearance. Because the
      erythrocyte is devoid of protein transport machinery, the parasite provides
      infrastructure for trafficking across membranes it traverses. In this study, we
      show that the P falciparum skeleton-binding protein 1 (PfSBP1) is required for
      transport of PfEMP1 to the P falciparum-infected erythrocyte surface. We present
      evidence that PfSBP1 functions at the parasitophorous vacuole membrane to load
      PfEMP1 into Maurer clefts during formation of these structures. Furthermore, the
      major reactivity of antibodies from malaria-exposed multigravid women is directed
      toward PfEMP1 because this is abolished in the absence of PfSBP1.

PMID- 17023586
TI  - B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance
      induction of anti-alphaGAL-producing B-1 cells.
AB  - B-1b cells produce IgM natural antibodies against alpha1-3Galbeta1-4GlcNAc
      (alphaGal). These can be tolerized by nonmyeloablative induction of mixed
      chimerism using alphaGal-positive (alphaGal+) donor marrow. We assessed the role
      of CR1/2 in this model for induction of tolerance of B-1b cells. Mixed
      hematopoietic chimerism was induced in alpha1-3galactosyltransferase (GalT-/-)
      and GalT-/-Cr2-/- mice with alphaGal+ BALB/c marrow donors. Anti-alphaGal Ab and
      anti-alphaGal Ab-producing B cells became undetectable in GalT-/- chimeras,
      whereas they persisted in chimeric GalT-/-Cr2-/- mice. To determine whether CR1/2
      expression on stromal cells and/or hematopoietic cells was critical for B-1-cell
      tolerance, we generated GalT-/- radiation chimeras in which CR1/CR2 was expressed
      on either stromal cells, hematopoietic cells, neither, or both. After induction
      of mixed chimerism from alphaGal+ allogeneic bone marrow (BM) donors, anti
      alphaGal-producing B cells were rendered tolerant in reconstituted recipients
      expressing only stromal CR1/CR2. Our results suggest a possible role for
      follicular dendritic cells that pick up immune complexes via CR1/CR2 receptors in
      the tolerization of B-1b cells.

PMID- 17023589
TI  - The advantages of a rolling foot in human walking.
AB  - The plantigrade human foot rolls over the ground during each walking step,
      roughly analogous to a wheel. The center of pressure progresses on the ground
      like a wheel of radius 0.3 L (leg length). We examined the effect of varying foot
      curvature on the mechanics and energetics of walking. We controlled curvature by
      attaching rigid arc shapes of various radii to the bottoms of rigid boots
      restricting ankle motion. We measured mechanical work performed on the center of
      mass (COM), and net metabolic rate, in human subjects (N=10) walking with seven
      arc radii from 0.02-0.40 m. Simple models of dynamic walking predict that
      redirection of COM velocity requires step-to-step transition work, decreasing
      quadratically with arc radius. Metabolic cost would be expected to change in
      proportion to mechanical work. We measured the average rate of negative work
      performed on the COM, and found that it followed the trend well (r2=0.95), with
      2.37 times as much work for small radii as for large. Net metabolic rate
      (subtracting quiet standing) also decreased with increasing arc radius to a
      minimum at 0.3 L, with a slight increase thereafter. Maximum net metabolic rate
      was 6.25 W kg(-1) (for small-radius arc feet), about 59% greater than the minimum
      rate of 3.93 W kg(-1), which in turn was about 45% greater than the rate in
      normal walking. Metabolic rate was fit reasonably well (r2=0.86) by a quadratic
      curve, but exceeded that expected from COM work for extreme arc sizes. Other
      factors appear to increase metabolic cost for walking on very small and very
      large arc feet. These factors may include effort expended to stabilize the joints
      (especially the knee) or to maintain balance. Rolling feet with curvature 0.3 L
      appear energetically advantageous for plantigrade walking, partially due to
      decreased work for step-to-step transitions.

PMID- 17023588
TI  - Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in
      vivo and in vitro.
AB  - Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether
      CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed
      no vascular defects during normal development or during neonatal oxygen-induced
      retinopathy. However, Cd151-null mice showed impaired pathologic angiogenesis in
      other in vivo assays (Matrigel plug, corneal micropocket, tumor implantation) and
      in the ex vivo aortic ring assay. Cd151-null mouse lung endothelial cells (MLECs)
      showed normal adhesion and proliferation, but marked alterations in vitro, in
      assays relevant to angiogenesis (migration, spreading, invasion, Matrigel
      contraction, tube and cable formation, spheroid sprouting). Consistent with these
      functional impairments, and with the close, preferential association of CD151
      with laminin-binding integrins, Cd151-null MLECs also showed selective signaling
      defects, particularly on laminin substrate. Adhesion-dependent activation of
      PKB/c-Akt, e-NOS, Rac, and Cdc42 was diminished, but Raf, ERK, p38 MAP kinase,
      FAK, and Src were unaltered. In Cd151-null MLECs, connections were disrupted
      between laminin-binding integrins and at least 5 other proteins. In conclusion,
      CD151 modulates molecular organization of laminin-binding integrins, thereby
      supporting secondary (ie, after cell adhesion) functions of endothelial cells,
      which are needed for some types of pathologic angiogenesis in vivo. Selective
      effects of CD151 on pathologic angiogenesis make it a potentially useful target
      for anticancer therapy.

PMID- 17023590
TI  - Selection on knockdown performance in Drosophila melanogaster impacts
      thermotolerance and heat-shock response differently in females and males.
AB  - We studied adaptive thermotolerance in replicate populations of Drosophila
      melanogaster artificially selected for high and low knockdown temperature
      (T(KD)), the upper temperature at which flies can no longer remain upright or
      locomote effectively. Responses to selection have generated High T(KD)
      populations capable of maintaining locomotor function at approximately 40 degrees
      C, and Low T(KD) populations with T(KD) of approximately 35 degrees C. We
      examined inducible knockdown thermotolerance, as well as inducible thermal
      survivorship, following a pretreatment heat-shock (known to induce heat-shock
      proteins) for males and females from the T(KD) selected lines. Both selection for
      knockdown and sex influenced inducible knockdown thermotolerance, whereas
      inducible thermal survivorship was influenced only by sex, and not by selection.
      Overall, our findings suggest that the relationships between basal and inducible
      thermotolerance are contingent upon the methods used to gauge thermotolerance, as
      well as the sex of the flies. Finally, we compared temporal profiles of the
      combined expression of two major heat-shock proteins, HSC70 and HSP70, during
      heat stress among the females and males from the selected T(KD) lines. The
      temporal profiles of the proteins differed between High and Low T(KD) females,
      suggesting divergence of the heat-shock response. We discuss a possible mechanism
      that may lead to the heat-shock protein patterns observed in the selected
      females.

PMID- 17023591
TI  - Regulation of stroke pattern and swim speed across a range of current velocities:
      diving by common eiders wintering in polynyas in the Canadian Arctic.
AB  - Swim speed during diving has important energetic consequences. Not only do costs
      increase as drag rises non-linearly with increasing speed, but speed also affects
      travel time to foraging patches and therefore time and energy budgets over the
      entire dive cycle. However, diving behaviour has rarely been considered in
      relation to current velocity. Strong tidal currents around the Belcher Islands,
      Nunavut, Canada, produce polynyas, persistent areas of open water in the sea ice
      which are important habitats for wildlife wintering in Hudson Bay. Some
      populations of common eiders Somateria mollissima sedentaria remain in polynyas
      through the winter where they dive to forage on benthic invertebrates. Strong
      tidal currents keep polynyas from freezing, but current velocity can exceed 1.5 m
      s(-1) and could influence time and energy costs of diving and foraging. Polynyas
      therefore provide naturally occurring flume tanks allowing investigation of
      diving strategies of free ranging birds in relation to current velocity. We used
      a custom designed sub-sea ice camera to non-invasively investigate over 150 dives
      to a depth of 11.3 m by a population of approximately 100 common eiders at
      Ulutsatuq polynya during February and March of 2002 and 2003. Current speed
      during recorded dives ranged from 0 to 1 m s(-1). As currents increased, vertical
      descent speed of eiders decreased, while descent duration and the number of wing
      strokes and foot strokes during descent to the bottom increased. However, nearly
      simultaneous strokes of wings and feet, and swim speed relative to the moving
      water, were maintained within a narrow range (2.28+/-0.23 Hz; 1.25+/-0.14 m s(
      1), respectively). This close regulation of swim speed over a range in current
      speed of 1.0 m s(-1) might correspond to efficient muscle contraction rates, and
      probably reduces work rates by avoiding rapidly increasing drag at greater
      speeds; however, it also increases travel time to benthic foraging patches.
      Despite regulation of average swim speed, high instantaneous speeds during
      oscillatory stroking can increase dive costs due to drag. While most diving birds
      have been considered either foot or wing propelled, eider ducks used both wing
      and foot propulsion during descent. Our observations indicate that the power
      phase of foot strokes coincides with the transition between upstroke and
      downstroke of the wings, when drag is greatest. Coordinated timing between foot
      and wing propulsion could therefore serve to maintain a steadier speed during
      descent and decrease the costs of diving. Despite tight regulation of stroke and
      swim speed patterns, descent duration and total number of foot and wing strokes
      during descent increase non-linearly with increasing current velocity, suggesting
      an increase in energetic costs of diving.

PMID- 17023592
TI  - Interspecific variation in beeswax as a biological construction material.
AB  - Beeswax is a multicomponent material used by bees in the genus Apis to house
      larvae and store honey and pollen. We characterized the mechanical properties of
      waxes from four honeybee species: Apis mellifera L., Apis andreniformis L., Apis
      dorsata L. and two subspecies of Apis cerana L. In order to isolate the material
      effects from the architectural properties of nest comb, we formed raw wax in to
      right, circular cylindrical samples, and compressed them in an electromechanical
      tensometer. From the resulting stress-strain curves, values for yield stress,
      yield strain, stress and strain at the proportional limit, stiffness, and
      resilience were obtained. Apis dorsata wax was stiffer and had a higher yield
      stress and stress at the proportional limit than all of the other waxes. The
      waxes of A. cerana and A. mellifera had intermediate strength and stiffness, and
      A. andreniformis wax was the least strong, stiff and resilient. All of the waxes
      had similar strain values at the proportional limit and yield point. The observed
      differences in wax mechanical properties correlate with the nesting ecology of
      these species. A. mellifera and A. cerana nest in cavities that protect the nest
      from environmental stresses, whereas the species with the strongest and stiffest
      wax, A. dorsata, constructs relatively heavy nests attached to branches of tall
      trees, exposing them to substantially greater mechanical forces. The wax of A.
      andreniformis was the least strong, stiff and resilient, and their nests have low
      masses relative to other species in the genus and, although not built in
      cavities, are constructed on lower, often shielded branches that can absorb the
      forces of wind and rain.

PMID- 17023593
TI  - Joint work and power for both the forelimb and hindlimb during trotting in the
      horse.
AB  - The net work of the limbs during constant speed over level ground should be zero.
      However, the partitioning of negative and positive work between the fore- and
      hindlimbs of a quadruped is not likely to be equal because the forelimb produces
      a net braking force while the hindlimb produces a net propulsive force. It was
      hypothesized that the forelimb would do net negative work while the hindlimb did
      net positive work during trotting in the horse. Because vertical and horizontal
      impulses remain unchanged across speeds it was hypothesized that net work of both
      limbs would be independent of speed. Additionally because the major mass of limb
      musculature is located proximally, it was hypothesized that proximal joints would
      do more work than distal joints. Kinetic and kinematic analysis were combined
      using inverse dynamics to calculate work and power for each joint of horses
      trotting at between 2.5 and 5.0 m s(-1). Work done by the hindlimb was indeed
      positive (consistently 0.34 J kg(-1) across all speeds), but, contrary to our
      hypothesis, net work by the forelimb was essentially zero (but also independent
      of trotting speed). The zero net work of the forelimb may be the consequence of
      our not being able to account, experimentally, for the negative work done by the
      extrinsic muscles connecting the scapula and the thorax. The distal three joints
      of both limbs behaved elastically with a period of energy absorption followed by
      energy return. Proximal forelimb joints (elbow and shoulder) did no net work,
      because there was very little movement of the elbow and shoulder during the
      portion of stance when an extensor moment was greatest. Of the two proximal
      hindlimb joints, the hip did positive work during the stride, generating energy
      almost throughout stance. The knee did some work, but like the forelimb proximal
      joints, had little movement during the middle of stance when the flexion moment
      was the greatest, probably serving to allow the efficient transmission of energy
      from the hip musculature to the ground.

PMID- 17023594
TI  - The control of anterior foregut motility during a larval molt of the moth Manduca
      sexta involves the modulation of presynaptic activity.
AB  - In the moth, Manduca sexta, anterior foregut motility is modulated during the
      larval-larval molts in order to control the timing of molting fluid (MF)
      ingestion. MF is the enzymatic mixture that destroys the outer cuticle so that it
      can be shed at the end of the molt. The onset of the larval-larval molt is
      characterized by a dramatic decline in the amplitude of the anterior foregut
      contractions so that MF is not prematurely ingested. As the end of the molt
      approaches, the robust contractions of the anterior foregut return and the MF is
      ingested, enabling the larva to free itself from its old cuticle. In the present
      study we examine possible mechanisms involved in modulating anterior foregut
      motility during a larval-larval molt. Our results reveal that the release of a
      blood-borne factor plays a role in the decline in anterior foregut peristaltic
      activity during the molt. This blood-borne factor reduces the efficacy of the
      presynaptic endings of the motorneurons, resulting in a reduction in the
      amplitude of the excitatory junctional potential (EJP) recorded from the anterior
      foregut musculature. We also present evidence that crustacean cardioactive
      peptide (CCAP) targets the motorneuron terminals and its actions are sufficient
      to trigger the dramatic increase in EJP amplitude and anterior foregut
      contractions. Finally, the surgical ablation of the subesophageal ganglion, which
      has been previously described to be a source of CCAP neurons and the CCAP
      projections to the anterior foregut region, blocks both the increase in anterior
      foregut motility and the ingestion of MF that normally occur at the end of a
      larval-larval molt.

PMID- 17023595
TI  - Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic
      vasoconstriction and hypoxic vasodilation.
AB  - How vertebrate blood vessels sense acute hypoxia and respond either by
      constricting (hypoxic vasoconstriction) or dilating (hypoxic vasodilation) has
      not been resolved. In the present study we compared the mechanical and electrical
      responses of select blood vessels to hypoxia and H2S, measured vascular H2S
      production, and evaluated the effects of inhibitors of H2S synthesis and addition
      of the H2S precursor, cysteine, on hypoxic vasoconstriction and hypoxic
      vasodilation. We found that: (1) in all vertebrate vessels examined to date,
      hypoxia and H2S produce temporally and quantitatively identical responses even
      though the responses vary from constriction (lamprey dorsal aorta; lDA), to
      dilation (rat aorta; rA), to multi-phasic (rat and bovine pulmonary arteries; rPA
      and bPA, respectively). (2) The responses of lDA, rA and bPA to hypoxia and H2S
      appear competitive; in the presence of one stimulus, the response to the other
      stimulus is substantially or completely eliminated. (3) Hypoxia and H2S produce
      the same degree of cell depolarization in bPA. (4) H2S is constitutively
      synthesized by lDA and bPA vascular smooth muscle. (5) Inhibition of H2S
      synthesis inhibits the hypoxic response of lDA, rA, rPA and bPA. (6) Addition of
      the H2S precursor, cysteine, doubles hypoxic contraction in lDA, prolongs
      contraction in bPA and alters the re-oxygenation response of rA. These studies
      suggest that H2S may serve as an O2 sensor/transducer in the vascular responses
      to hypoxia. In this model, the concentration of vasoactive H2S in the vessel is
      governed by the balance between endogenous H2S production and its oxidation by
      available O2.

PMID- 17023596
TI  - Sub-lethal and chronic salinity tolerances of three freshwater insects: Cloeon
      sp. and Centroptilum sp. (Ephemeroptera: Baetidae) and Chironomus sp. (Diptera:
      Chironomidae).
AB  - Increased salinity in rivers and streams is a serious environmental concern, and
      in Australia there is growing information about the acute tolerances to salinity
      for freshwater macroinvertebrates, but much less information about chronic and
      sub-lethal tolerances. The effects of increased salinity on the growth and
      survival of two mayflies, Cloeon sp. and Centroptilum sp. and one midge
      Chironomus sp. are reported. In both mayfly species survival was variable.
      Complete mortality was observed in salinities with electrical conductivity of 10
      mS cm(-1) and higher. Salinities causing chronic mortality in mayflies were
      measured as 21-day LC50, and ranged from 0.90 to 2.7 mS cm(-1). Growth rates were
      not significantly different between treatments. In Chironomus, salinity affected
      the mean number emerging as flying adults as well as the time to emergence. An
      inverted 'U' shape response was observed for percentage emergence, with the
      greatest numbers emerging at intermediate salinities (0.65-5.0 mS cm(-1)). No
      emergence occurred at salinities of 20 mS cm(-1) and higher. Time to emergence
      was delayed by 15-88% with increased salinity, however the size of emerged adults
      was the same for all treatments. Growth rates were reduced with increased
      salinity, showing a slow, steady reduction up to 10 mS cm(-1) then a steep
      decline between 10 and 15 mS cm(-1). The implications of altered growth rates and
      changes in developmental times are discussed. This study illustrates the
      variability in responses to increased salinity, and highlights the need to
      continue studying sub-lethal and chronic exposures in a range of freshwater
      invertebrates, in order to predict impacts of salinisation on freshwater
      biodiversity.

PMID- 17023597
TI  - Effects of oleic acid on the high threshold barium current in seabass
      Dicentrarchus labrax ventricular myocytes.
AB  - The present study employed a patch clamp technique in isolated seabass
      ventricular myocytes to investigate the hypothesis that oleic acid (OA), a mono
      unsaturated fatty acid, can exert direct effects upon whole-cell barium currents.
      Acute application of free OA caused a dose-dependent depression of the whole-cell
      barium current that was evoked by a voltage step to 0 mV from a holding potential
      of -80 mV. The derived 50% inhibitory concentration (IC50) was 12.49+/-0.27
      micromol l(-1). At a concentration of 30 micromol l(-1), OA significantly reduced
      the current density to about 45% of control values, but did not modify either the
      shape of the current-density voltage relationship or the apparent reversal
      potential. In addition, OA did not modify the voltage dependence of either steady
      state inactivation or activation curves. Taken together, these results indicate
      that physiological concentrations of free OA decrease the conductance of the L
      type inward current, without altering its properties of selectivity and its
      voltage dependence. The inhibitory effect of OA upon the L-type calcium channel
      may translate, in vivo, into a protective effect against arrhythmias induced by
      Ca2+ overload.

PMID- 17023598
TI  - Plasticity of osmoregulatory function in the killifish intestine: drinking rates,
      salt and water transport, and gene expression after freshwater transfer.
AB  - We have explored intestinal function in the euryhaline killifish Fundulus
      heteroclitus after transfer from brackish water (10% seawater) to fresh water.
      Plasma Na+ and Cl- concentrations fell at 12 h post-transfer, but recovered by 7
      days. Drinking rate decreased substantially at 12 h (32% of control value) and
      remained suppressed after 3 and 7 days in fresh water (34 and 43%). By contrast,
      there was a transient increase in the capacity for water absorption measured
      across isolated intestines in vitro (3.3- and 2.6-fold at 12 h and 3 days), which
      returned to baseline after 7 days. These changes in water absorption could be
      entirely accounted for by changes in net ion flux: there was an extremely strong
      correlation (R2=0.960) between water absorption and the sum of net Na+ and net Cl
      fluxes (3.42+/-0.10 microl water micromol(-1) ion). However, enhanced ion
      transport across the intestine in fresh water would probably not increase water
      uptake in vivo, because the drinking rate was far less than the capacity for
      water absorption across the intestine. The increased intestinal ion absorption
      after freshwater transfer may instead serve to facilitate ion absorption from
      food when it is present in the gut. Modulation of net ion flux occurred without
      changes in mRNA levels of many ion transporters (Na+/K+-ATPase alpha(1a),
      carbonic anhydrase 2, CFTR Cl- channel, Na+/K+/2Cl- cotransporter 2, and the
      signalling protein 14-3-3a), and before a measured increase in Na+/K+-ATPase
      activity at 3 days, suggesting that there is some other mechanism responsible for
      increasing ion transport. Interestingly, net Cl- flux always exceeded net Na+
      flux, possibly to help maintain Cl- balance and/or facilitate bicarbonate
      excretion. Our results suggest that intestinal NaCl absorption from food is
      important during the period of greatest ionic disturbance after transfer to fresh
      water, and provide further insight into the mechanisms of euryhalinity in
      killifish.

PMID- 17023599
TI  - The landing-take-off asymmetry in human running.
AB  - In the elastic-like bounce of the body at each running step the muscle-tendon
      units are stretched after landing and recoil before take-off. For convenience,
      both the velocity of the centre of mass of the body at landing and take-off, and
      the characteristics of the muscle-tendon units during stretching and recoil, are
      usually assumed to be the same. The deviation from this symmetrical model has
      been determined here by measuring the mechanical energy changes of the centre of
      mass of the body within the running step using a force platform. During the
      aerial phase the fall is greater than the lift, and also in the absence of an
      aerial phase the transduction between gravitational potential energy and kinetic
      energy is greater during the downward displacement than during the lift. The peak
      of kinetic energy in the sagittal plane is attained thanks to gravity just prior
      to when the body starts to decelerate downwards during the negative work phase.
      In contrast, a lower peak of kinetic energy is attained, during the positive work
      phase, due to the muscular push continuing to accelerate the body forwards after
      the end of the acceleration upwards. Up to a speed of 14 km h(-1) the positive
      external work duration is greater than the negative external work duration,
      suggesting a contribution of muscle fibres to the length change of the muscle
      tendon units. Above this speed, the two durations (<0.1 s) are similar,
      suggesting that the length change is almost totally due to stretch-recoil of the
      tendons with nearly isometrically contracting fibres.

PMID- 17023600
TI  - What explains the trot-gallop transition in small mammals?
AB  - The transition from trot to gallop in quadruped mammals has been widely
      hypothesized to be a strategy to minimize the energetic costs of running. This
      view, however, has been challenged by some experimental evidence suggesting
      instead that this transition might be triggered by mechanical cues, and would
      occur when musculoskeletal stresses reach a certain critical value. All previous
      experiments to test those hypotheses have used relatively large species and their
      results, therefore, may not be applicable to small mammals. In this study we
      evaluated the effect of carrying loads on the locomotor energetics and gait
      transitions of the rodent Octodon degus running on a treadmill. Metabolic rate
      and cost of transport increased about 30% with a 20% increment in body mass. This
      increment was higher than expectations based on other mammals, where energy
      consumption increases in proportion to the added mass, but similar to the
      response of humans to loads. No abrupt change of energy consumption between gaits
      was observed and therefore no evidence was found to support the energetic
      hypothesis. The trot-gallop transition speed did not vary when subjects were
      experimentally loaded, suggesting that the forces applied to the musculoskeletal
      system do not trigger gait transition.

PMID- 17023601
TI  - Downregulation of aquaporins 1 and 5 in nasal gland by osmotic stress in
      ducklings, Anas platyrhynchos: implications for the production of hypertonic
      fluid.
AB  - Using primers against highly conserved regions of mammalian and bird aquaporins
      in RT-PCR experiments, we amplified products derived from duck (Anas
      platyrhynchos) nasal gland RNA that were identified as homologues of mammalian
      and chicken aquaporin 1 and aquaporin 5 cDNAs by sequencing. Using digoxigenin
      labelled probes derived from these PCR products in northern blot analyses of mRNA
      isolated from nasal glands of untreated (naive) or osmotically stressed ducklings
      (replacement of drinking water with a 1% NaCl solution), we observed a decrease
      in aquaporin 1 (AQP1) and aquaporin 5 (AQP5) mRNA abundance (by approximately
      40%) during saline adaptation in the animals. Western blot analysis of AQP1 and
      AQP5 expression in the glands revealed that protein abundance decreased in a
      similar fashion. Immunohistochemical analysis of AQP1 distribution in
      cryosections of nasal gland indicated that AQP1 is mainly expressed in
      endothelial cells of the capillaries, but definitely not in the secretory or
      ductal cells of the gland. AQP5 distribution in the gland, however, seems to be
      different, since staining was exclusively observed in apical and basolateral
      plasma membranes of individual epithelial cells of the primary and central ducts,
      which collect fluid from the secretory tubules. The observations are consistent
      with the hypothesis that strongly hyperosmotic fluid is produced by the secretory
      cells at very low (unstimulated gland) or high (activated gland) rates. In the
      unstimulated gland, secretions may be diluted by aquaporin-mediated transcellular
      water flux while passing through the ductal system flushing the glandular ducts,
      thereby potentially preventing ascending infections. In the activated gland,
      however, downregulation of aquaporins in capillaries and duct cells may prevent
      dilution of the initially secreted fluid, enabling the animals to excrete large
      volumes of a highly concentrated salt solution.

PMID- 17023602
TI  - The role of the lateral line and vision on body kinematics and hydrodynamic
      preference of rainbow trout in turbulent flow.
AB  - The ability to detect water flow using the hair cells of the lateral line system
      is a unique feature found in anamniotic aquatic vertebrates. Fishes use their
      lateral line to locate prey, escape from predators and form cohesive schooling
      patterns. Despite the prevalence of complex flows in nature, almost nothing is
      known about the function of the lateral line and its relationship to other
      sensory modalities for freely swimming fishes in turbulent flows. Past studies
      indicate that under certain conditions the lateral line is not needed to swim
      steadily in uniform flow. This paper examines how the lateral line and vision
      affect body kinematics and hydrodynamic habitat selection of rainbow trout
      (Oncorhynchus mykiss) exposed to vortices generated behind a cylinder. Trout
      Karman gaiting (i.e. exploiting vortices to hold station in a vortex street) with
      a pharmacologically blocked lateral line display altered kinematics; body
      wavelength and wave speed increase compared to control animals. When visual cues
      are withheld by performing experiments in the dark, almost all Karman gait
      kinematics measured for fish with and without a functional lateral line are the
      same. The lateral line, rather than vision, plays a larger role in affecting body
      kinematics when trout hold station in a vortex street. Trout show a preference to
      Karman gait in the light but not in the dark, which may be attributed to
      physiological state rather than hydrodynamic or sensorimotor reasons. In the
      dark, trout both with and without a functional lateral line hold station near the
      downstream suction region of the cylinder wake (i.e. entraining) and avoid the
      vortex street. Vision therefore plays a larger role in the preference to
      associate with a turbulent vortex street. Trout in the light with a blocked
      lateral line show individual variation in their preference to Karman gait or
      entrain. In the dark, entraining trout with an intact lateral line will alternate
      between right and left sides of the cylinder throughout the experiment, showing
      an ability to explore their environment. By contrast, when the lateral line is
      blocked these fish display a strong fidelity to one side of the cylinder and are
      not inclined to explore other regions of the flow tank. Both entraining and
      Karman gaiting probably represent energetically favorable strategies for holding
      station relative to the earth frame of reference in fast flows. The ability to
      decipher how organisms collect and process sensory input from their environment
      has great potential in revealing the mechanistic basis of how locomotor behaviors
      are produced as well as how habitat selection is modulated.

PMID- 17023603
TI  - Foraging energetics of a nectar-feeding ant: metabolic expenditure as a function
      of food-source profitability.
AB  - We examined the quantitative relationship between the energetic costs and
      benefits of nectar collection by nectar-feeding ants, Camponotus rufipes. In the
      laboratory, individual workers were trained to visit an artificial feeder that
      provided a sucrose solution of 1%, 5%, 10%, 30% or 50% at controlled flows, in a
      similar span range to those observed in natural nectar sources. We measured
      foraging times, nectar loads collected, and CO(2) production during actual
      feeding, as an indication of the energy expenditure for a single forager. Results
      show an increase in individual metabolic rates with increasing flow rate of sugar
      solution, but no dependence on sucrose concentration. This increase in metabolic
      expenditure does not depend on the crop load attained while feeding, as
      intuitively expected, and is therefore a result of an increased activity brought
      about by the food-source profitability experienced by the forager. The energy
      gained during collection of sugar solution is always higher than the energy spent
      by the ant. Even with a food source of lower quality than a natural source, the
      ants gain ca. tenfold of what they spend. Based on a simplified model, we
      calculated that foragers of C. rufipes could travel from 0.5 to 9 km with the
      energy gained in a single foraging trip only. These results suggest that
      decreasing foraging time is more important than increasing individual energetic
      efficiency when workers of the nectar-feeding ant C. rufipes decide to stop
      drinking and return to the nest with partial crop loads.

PMID- 17023604
TI  - Seasonal acquisition of chill tolerance and restructuring of membrane
      glycerophospholipids in an overwintering insect: triggering by low temperature,
      desiccation and diapause progression.
AB  - Adults of the insect Pyrrhocoris apterus acquire chill tolerance through the
      process of autumnal acclimatization. Field and laboratory experiments were
      conducted to separate the triggering effects of low temperatures, desiccation and
      diapause progression on the physiological characteristics related to chill
      tolerance with emphasis on the restructuring of glycerophospholipid (GPL)
      composition. Changes in relative proportions of major molecular species of
      glycerophosphoethanolamines (GPEtns) and glycerophosphocholines (GPChols) in
      thoracic muscle and fat body tissues were followed using HPLC coupled to
      electrospray ionisation mass spectrometry. The increase in relative proportion of
      1-palmitoyl-2-linoleyl-sn-GPEtn at the expense of 1,2-dilinoleyl-sn-GPChol was
      the most prominent feature of the complex change observed in both tissues during
      autumnal acclimatization in the field. The relative proportion of total GPEtns
      increased, while the proportion of total GPChols decreased. The relative
      proportion of unsaturated fatty acyls slightly decreased. A similar restructuring
      response was seen during acclimatization in the field and cold acclimation in the
      laboratory. By contrast, the GPL changes related to desiccation and diapause
      progression were relatively small, differed qualitatively from the cold
      acclimation response, and were accompanied with no increase of chill tolerance.
      Other features of autumnal acclimatization, i.e. depression of supercooling
      capacity and accumulation of polyhydric alcohols, were also triggered solely by
      low temperatures.

PMID- 17023605
TI  - Tuning the drum: the mechanical basis for frequency discrimination in a
      Mediterranean cicada.
AB  - Cicadas are known to use sound to find a mate. While the mechanism employed by
      male cicadas to generate loud calling songs has been described in detail, little
      information exists to explain how their ears work. Using microscanning laser
      Doppler vibrometry, the tympanal vibrations in the cicada Cicadatra atra are
      measured in response to acoustic playbacks. The topographically accurate optical
      measurements reveal the vibrational behaviour of the anatomically complex
      tympanal membrane. Notably, the tympanal ridge, a distinct structural element of
      the tympanum that is a link to the receptor cells, undergoes mechanical
      vibrations reminiscent of a travelling wave. In effect, the frequency for which
      the maximum deflection amplitude is observed regularly decreases from the apex to
      the base of the ridge. It is also shown that whilst female ears are mechanically
      tuned to the male's song, the male's tympanum is only partially tuned to its own
      song. This study establishes the presence of a peripheral auditory mechanism that
      can potentially process auditory frequency analysis. In view of the importance of
      acoustic signalling in cicadas, this unconventional tympanal mechanism may be
      employed in the context of species recognition and sexual selection.

PMID- 17023606
TI  - Delayed development and lifespan extension as features of metabolic lifestyle
      alteration in C. elegans under dietary restriction.
AB  - Studies of the model organism Caenorhabditis elegans have almost exclusively
      utilized growth on a bacterial diet. Such culturing presents a challenge to
      automation of experimentation and introduces bacterial metabolism as a secondary
      concern in drug and environmental toxicology studies. Axenic cultivation of C.
      elegans can avoid these problems, yet past work suggests that axenic growth is
      unhealthy for C. elegans. Here we employ a chemically defined liquid medium to
      culture C. elegans and find development slows, fecundity declines, lifespan
      increases, lipid and protein stores decrease, and gene expression changes
      relative to that on a bacterial diet. These changes do not appear to be random
      pathologies associated with malnutrition, as there are no developmental delays
      associated with starvation, such as L1 or dauer diapause. Additionally,
      development and reproductive period are fixed percentages of lifespan regardless
      of diet, suggesting that these alterations are adaptive. We propose that C.
      elegans can exist as a healthy animal with at least two distinct adult life
      histories. One life history maximizes the intrinsic rate of population increase,
      the other maximizes the efficiency of exploitation of the carrying capacity of
      the environment. Microarray analysis reveals increased transcript levels of daf
      16 and downstream targets and past experiments demonstrate that DAF-16 (FOXO)
      acting on downstream targets can influence all of the phenotypes we see altered
      in maintenance medium. Thus, life history alteration in response to diet may be
      modulated by DAF-16. Our observations introduce a powerful system for automation
      of experimentation on healthy C. elegans and for systematic analysis of the
      profound impact of diet on animal physiology.

PMID- 17023607
TI  - The variable colours of the fiddler crab Uca vomeris and their relation to
      background and predation.
AB  - Colour changes in fiddler crabs have long been noted, but a functional
      interpretation is still lacking. Here we report that neighbouring populations of
      Uca vomeris in Australia exhibit different degrees of carapace colours, which
      range from dull mottled to brilliant blue and white. We determined the spectral
      characteristics of the mud substratum and of the carapace colours of U. vomeris
      and found that the mottled colours of crabs are cryptic against this background,
      while display colours provide strong colour contrast for both birds and crabs,
      but luminance contrast only for a crab visual system. We tested whether crab
      populations may become cryptic under the influence of bird predation by counting
      birds overflying or feeding on differently coloured colonies. Colonies with
      cryptically coloured crabs indeed experience a much higher level of bird
      presence, compared to colourful colonies. We show in addition that colourful crab
      individuals subjected to dummy bird predation do change their body colouration
      over a matter of days. The crabs thus appear to modify their social signalling
      system depending on their assessment of predation risk.

PMID- 17023608
TI  - Locomotor kinetics and kinematics on inclines and declines in the gray short
      tailed opossum Monodelphis domestica.
AB  - Small terrestrial animals continually encounter sloped substrates when moving
      about their habitat; therefore, it is important to understand the mechanics and
      kinematics of locomotion on non-horizontal substrates as well as on level
      terrain. To this end, we trained gray short-tailed opossums (Monodelphis
      domestica) to move along level, 30 degrees inclined, and 30 degrees declined
      trackways instrumented with a force platform. Vertical, craniocaudal and
      mediolateral impulses, peak vertical forces, and required coefficient of friction
      (mu(req)) of individual limbs were calculated. Two high speed video cameras were
      used to simultaneously capture whole limb craniocaudal and mediolateral angles at
      limb touchdown, midstance and lift-off. Patterns on the level terrain were
      typical for non-primate quadrupeds: the forelimbs supported the majority of the
      body weight, forelimbs were net braking and hindlimbs net propulsive, and both
      limb pairs exerted small laterally directed impulses. M. domestica moved more
      slowly on sloped substrates in comparison to level locomotion, and exhibited a
      greater mu(req). On inclines, both limb pairs were more protracted at touchdown
      and more retracted at lift-off, fore- and hindlimbs had equal roles in body
      weight support, forelimbs exerted greater propulsive impulse than hindlimbs, and
      mu(req) was greater in the forelimbs than in hindlimbs. On declines, only the
      forelimbs were more protracted at touchdown; forelimbs supported the great
      majority of body weight while they generated nearly all of the braking impulse
      and, despite the disparity in fore- vs hindlimb function on the decline, mu(req)
      was not significantly different between limbs. These differences on the inclined
      and declined surfaces most likely result from (1) the location of the opossums'
      center of mass, which is closer to the forelimbs than to the hindlimbs, and (2)
      the greater functional range of the forelimbs versus the hindlimbs.

PMID- 17023609
TI  - Cardiovascular changes under normoxic and hypoxic conditions in the air-breathing
      teleost Synbranchus marmoratus: importance of the venous system.
AB  - Synbranchus marmoratus is a facultative air-breathing fish, which uses its buccal
      cavity as well as its gills for air-breathing. S. marmoratus shows a very
      pronounced tachycardia when it surfaces to air-breathe. An elevation of heart
      rate decreases cardiac filling time and therefore may cause a decline in stroke
      volume (V(S)), but this can be compensated for by an increase in venous tone to
      maintain stroke volume. Thus, the study on S. marmoratus was undertaken to
      investigate how stroke volume and venous function are affected during air
      breathing. To this end we measured cardiac output (Q), heart rate (f(H)), central
      venous blood pressure (P(CV)), mean circulatory filling pressure (MCFP), and
      dorsal aortic blood pressures (P(DA)) in S. marmoratus. Measurements were
      performed in aerated water (P(O2)>130 mmHg), when the fish alternated between
      gill ventilation and prolonged periods of apnoeas, as well as during hypoxia
      (P(O2)<or=50 mmHg), when the fish changed from gill ventilation to air-breathing.
      Q increased significantly during gill ventilation compared to apnoea in aerated
      water through a significant increase in both f(H) and V(S). P(CV) and MCFP also
      increased significantly. During hypoxia, when the animals surface to ventilate
      air, we found a marked rise in f(H), P(CV), MCFP, Q and V(S), whereas P(DA)
      decreased significantly. Simultaneous increases in P(CV) and MCFP in aerated, as
      well as in hypoxic water, suggests that the venous system plays an important
      regulatory role for cardiac filling and V(S) in this species. In addition, we
      investigated adrenergic regulation of the venous system through bolus infusions
      of adrenergic agonists (adrenaline, phenylephrine and isoproterenol; 2 microg kg(
      1)). Adrenaline and phenylephrine caused a marked rise in P(CV) and MCFP, whereas
      isoproterenol led to a marked decrease in P(CV), and tended to decrease MCFP.
      Thus, it is evident that stimulation of both alpha- and beta-adrenoreceptors
      affects venous tone in S. marmoratus.

PMID- 17023610
TI  - Escape responses in juvenile Atlantic cod Gadus morhua L.: the effects of
      turbidity and predator speed.
AB  - We examined the effect of turbidity (0.5-14 beam attenuation m(-1)) and predator
      attack speed (150 and 296 cm s(-1)) on escape responses of juvenile cod Gadus
      morhua in the laboratory. We triggered escape responses using a predator model
      and measured escape timing, direction and locomotor performance. We also measured
      responsiveness and estimated the likelihood of fish escaping the ;predator
      attack' (putative escape success, PES). Turbidity affected both PES and the type
      of escape response used by the fish, but these effects depended on predator
      speed. PES for the fast predator attack declined from 73% in clear water to 21%
      in highly turbid water, due to decreased responsiveness and poorly timed escapes.
      Intermediate turbidity enhanced PES and responsiveness to the slow predator
      attack. Locomotor performance was reduced by turbidity, whereas predator speed
      had the opposite effect. Our results suggest that both predator attack speed and
      turbidity have important roles in determining the vulnerability of fish attacked
      by piscivorous predators.

PMID- 17023611
TI  - Barium isotopes in chondritic meteorites: implications for planetary reservoir
      models.
AB  - High-precision barium isotope measurements yielded differences of up to 25 parts
      per million in the 137Ba/136Ba ratio and 60 parts per million in the 138Ba/136Ba
      ratio between chondrites and Earth. These differences probably arose from
      incomplete mixing of nucleosynthetic material in the solar nebula. Chondritic
      meteorites have a slight excess of supernova-derived material as compared to
      Earth, demonstrating that the solar nebula was not perfectly homogenized upon
      formation.

PMID- 17023612
TI  - Solar nebula heterogeneity in p-process samarium and neodymium isotopes.
AB  - Bulk carbonaceous chondrites display a deficit of approximately 100 parts per
      million (ppm) in 144Sm with respect to other meteorites and terrestrial
      standards, leading to a decrease in their 142Nd/144Nd ratios by approximately 11
      ppm. The data require that samarium and neodymium isotopes produced by the p
      process associated with photodisintegration reactions in supernovae were
      heterogeneously distributed in the solar nebula. Other samarium and neodymium
      isotopes produced by rapid neutron capture (r process) in supernovae and by slow
      neutron capture (s process) in red giants were homogeneously distributed. The
      supernovae sources supplying the p- and r-process nuclides to the solar nebula
      were thus disconnected or only weakly connected.

PMID- 17023613
TI  - From plant traits to plant communities: a statistical mechanistic approach to
      biodiversity.
AB  - We developed a quantitative method, analogous to those used in statistical
      mechanics, to predict how biodiversity will vary across environments, which plant
      species from a species pool will be found in which relative abundances in a given
      environment, and which plant traits determine community assembly. This provides a
      scaling from plant traits to ecological communities while bypassing the
      complications of population dynamics. Our method treats community development as
      a sorting process involving species that are ecologically equivalent except with
      respect to particular functional traits, which leads to a constrained random
      assembly of species; the relative abundance of each species adheres to a general
      exponential distribution as a function of its traits. Using data for eight
      functional traits of 30 herbaceous species and community-aggregated values of
      these traits in 12 sites along a 42-year chronosequence of secondary succession,
      we predicted 94% of the variance in the relative abundances.

PMID- 17023614
TI  - Diminishing reciprocal fairness by disrupting the right prefrontal cortex.
AB  - Humans restrain self-interest with moral and social values. They are the only
      species known to exhibit reciprocal fairness, which implies the punishment of
      other individuals' unfair behaviors, even if it hurts the punisher's economic
      self-interest. Reciprocal fairness has been demonstrated in the Ultimatum Game,
      where players often reject their bargaining partner's unfair offers. Despite
      progress in recent years, however, little is known about how the human brain
      limits the impact of selfish motives and implements fair behavior. Here we show
      that disruption of the right, but not the left, dorsolateral prefrontal cortex
      (DLPFC) by low-frequency repetitive transcranial magnetic stimulation
      substantially reduces subjects' willingness to reject their partners'
      intentionally unfair offers, which suggests that subjects are less able to resist
      the economic temptation to accept these offers. Importantly, however, subjects
      still judge such offers as very unfair, which indicates that the right DLPFC
      plays a key role in the implementation of fairness-related behaviors.

PMID- 17023615
TI  - Prying open the black box.

PMID- 17023616
TI  - Genetics. Seeing a 'plot,' deCODE sues to block a DNA research center.

PMID- 17023617
TI  - U.S. competitiveness. Hopes for innovation bill rest on lame-duck Congress.

PMID- 17023618
TI  - Polar research. U.S. needs new icebreakers, report tells Congress.

PMID- 17023620
TI  - Nobel Prize in Physics. Astrophysicists lauded for first baby picture of the
      universe.

PMID- 17023621
TI  - Astronomy. Speedy planets near galactic center show sun's region is no fluke.

PMID- 17023619
TI  - Nobel Prize in Physiology or Medicine. Method to silence genes earns loud praise.

PMID- 17023622
TI  - Geochemistry. Has lazy mixing spoiled the primordial stew?

PMID- 17023624
TI  - France. Presidential hopefuls discover a new issue: science.

PMID- 17023623
TI  - Nonlinear dynamics. Bizarrely, adding delay to delay produces synchronization.

PMID- 17023625
TI  - Biodefense. House passes plan for drug, vaccine R&D.

PMID- 17023626
TI  - John Niederhuber. A physician-scientist takes the helm of NCI.

PMID- 17023627
TI  - John Niederhuber. Budgets, patients, managing conflicts.

PMID- 17023628
TI  - Neurodegenerative diseases. Picking apart the causes of mysterious dementias.

PMID- 17023630
TI  - American Chemical Society meeting. Power to the (poor) people.

PMID- 17023629
TI  - Science policy. Priorities needed for nano-risk research and development.

PMID- 17023631
TI  - American Chemical Society meeting. Cut-and-copy approach clones nanotubes.

PMID- 17023632
TI  - American Chemical Society meeting. Snapshots from the meeting.

PMID- 17023633
TI  - Post-fire logging debate ignores many issues.

PMID- 17023634
TI  - Preventing HIV/AIDS in adolescents.

PMID- 17023635
TI  - On purpose in conservation.

PMID- 17023636
TI  - Comment on "Pairing and phase separation in a polarized Fermi gas".
AB  - Partridge et al. (Reports, 27 January 2006, p. 503) reported pairing and phase
      separation in a polarized Fermi gas. We argue that it is not possible to
      distinguish the superfluid from the normal regimes in the presented data, or to
      discern which clouds were phase-separated. Some of the reported conclusions are
      inconsistent with recent experiments.

PMID- 17023637
TI  - Public health. Genomics and medicine at a crossroads in Chernobyl.

PMID- 17023638
TI  - Cell signaling. The double life of a transcription factor takes it outside the
      nucleus.

PMID- 17023639
TI  - Chemistry. Mass spectrometry: bottom-up or top-down?

PMID- 17023640
TI  - Evolution. Fossil record reveals tropics as cradle and museum.

PMID- 17023642
TI  - Chemistry. Boron goes on the attack.

PMID- 17023641
TI  - Cancer. Cancer immunotherapy is more than a numbers game.

PMID- 17023643
TI  - Astronomy. Galactic prominences on the rise.

PMID- 17023644
TI  - Eppendorf 2006 winner. A dedicated system for processing faces.

PMID- 17023645
TI  - Eppendorf 2006 winner. 2006 grand prize winner.

PMID- 17023647
TI  - An enterprising approach to brain science.

PMID- 17023648
TI  - Vision's grand theorist.

PMID- 17023649
TI  - Modeling single-neuron dynamics and computations: a balance of detail and
      abstraction.
AB  - The fundamental building block of every nervous system is the single neuron.
      Understanding how these exquisitely structured elements operate is an integral
      part of the quest to solve the mysteries of the brain. Quantitative mathematical
      models have proved to be an indispensable tool in pursuing this goal. We review
      recent advances and examine how single-cell models on five levels of complexity,
      from black-box approaches to detailed compartmental simulations, address key
      questions about neural dynamics and signal processing.

PMID- 17023650
TI  - Neuronal computations with stochastic network states.
AB  - Neuronal networks in vivo are characterized by considerable spontaneous activity,
      which is highly complex and intrinsically generated by a combination of single
      cell electrophysiological properties and recurrent circuits. As seen, for
      example, during waking compared with being asleep or under anesthesia, neuronal
      responsiveness differs, concomitant with the pattern of spontaneous brain
      activity. This pattern, which defines the state of the network, has a dramatic
      influence on how local networks are engaged by inputs and, therefore, on how
      information is represented. We review here experimental and theoretical evidence
      of the decisive role played by stochastic network states in sensory
      responsiveness with emphasis on activated states such as waking. From single
      cells to networks, experiments and computational models have addressed the
      relation between neuronal responsiveness and the complex spatiotemporal patterns
      of network activity. The understanding of the relation between network state
      dynamics and information representation is a major challenge that will require
      developing, in conjunction, specific experimental paradigms and theoretical
      frameworks.

PMID- 17023651
TI  - Biologically based computational models of high-level cognition.
AB  - Computer models based on the detailed biology of the brain can help us understand
      the myriad complexities of human cognition and intelligence. Here, we review
      models of the higher level aspects of human intelligence, which depend critically
      on the prefrontal cortex and associated subcortical areas. The picture emerging
      from a convergence of detailed mechanistic models and more abstract functional
      models represents a synthesis between analog and digital forms of computation.
      Specifically, the need for robust active maintenance and rapid updating of
      information in the prefrontal cortex appears to be satisfied by bistable
      activation states and dynamic gating mechanisms. These mechanisms are fundamental
      to digital computers and may be critical for the distinctive aspects of human
      intelligence.

PMID- 17023652
TI  - Generation of simian-tropic HIV-1 by restriction factor evasion.
AB  - Because HIV-1 does not infect most nonhuman primates, animal modeling of human
      HIV infection and AIDS has primarily consisted of experimentally infecting
      macaques with related simian immunodeficiency viruses (SIVMAC). However, the
      usefulness of such models is limited by the substantial divergence between SIVMAC
      and HIV-1. We derived an HIV-1-based virus that includes only small portions of
      SIVMAC yet replicates robustly in both transformed and primary rhesus macaque T
      cells. Derivation of simian-tropic HIV-1 (stHIV-1) has important implications for
      understanding primate lentivirus zoonosis and should allow the development of
      improved animal models for studies of AIDS and the evaluation of vaccines and
      treatments.

PMID- 17023653
TI  - Out of the tropics: evolutionary dynamics of the latitudinal diversity gradient.
AB  - The evolutionary dynamics underlying the latitudinal gradient in biodiversity
      have been controversial for over a century. Using a spatially explicit approach
      that incorporates not only origination and extinction but immigration, a global
      analysis of genera and subgenera of marine bivalves over the past 11 million
      years supports an "out of the tropics" model, in which taxa preferentially
      originate in the tropics and expand toward the poles without losing their
      tropical presence. The tropics are thus both a cradle and a museum of
      biodiversity, contrary to the conceptual dichotomy dominant since 1974; a
      tropical diversity crisis would thus have profound evolutionary effects at all
      latitudes.

PMID- 17023654
TI  - Molecular loops in the galactic center: evidence for magnetic flotation.
AB  - The central few hundred parsecs of the Milky Way host a massive black hole and
      exhibit very violent gas motion and high temperatures in molecular gas. The
      origin of these properties has been a mystery for the past four decades. Wide
      field imaging of the (12)CO (rotational quantum number J = 1 to 0) 2.6-millimeter
      spectrum has revealed huge loops of dense molecular gas with strong velocity
      dispersions in the galactic center. We present a magnetic flotation model to
      explain that the formation of the loops is due to magnetic buoyancy caused by the
      Parker instability. The model has the potential to offer a coherent explanation
      for the origin of the violent motion and extensive heating of the molecular gas
      in the galactic center.

PMID- 17023655
TI  - Extending top-down mass spectrometry to proteins with masses greater than 200
      kilodaltons.
AB  - For characterization of sequence and posttranslational modifications, molecular
      and fragment ion mass data from ionizing and dissociating a protein in the mass
      spectrometer are far more specific than are masses of peptides from the protein's
      digestion. We extend the approximately 500-residue, approximately 50-kilodalton
      (kD) dissociation limitation of this top-down methodology by using electrospray
      additives, heated vaporization, and separate noncovalent and covalent bond
      dissociation. This process can cleave 287 interresidue bonds in the termini of a
      1314-residue (144-kD) protein, specify previously unidentified disulfide bonds
      between 8 of 27 cysteines in a 1714-residue (200-kD) protein, and correct
      sequence predictions in two proteins, one with 2153 residues (229 kD).

PMID- 17023656
TI  - Boryllithium: isolation, characterization, and reactivity as a boryl anion.
AB  - Nucleophilic, anionic boryl compounds are long-sought but elusive species. We
      report that reductive cleavage of the boron-bromine bond in N,N'-bis(2,6
      diisopropylphenyl)-2-bromo-2,3-dihydro-1H-1,3,2-diazaborole by lithium
      naphthalenide afforded the corresponding boryllithium, which is isoelectronic
      with an N-heterocyclic carbene. The structure of the boryllithium determined by x
      ray crystallography was consistent with sp(2) boron hybridization and revealed a
      boron-lithium bond length of 2.291 +/- 0.006 angstroms. The structural similarity
      between this compound and the calculated free boryl anion suggests that the boron
      atom has an anionic charge. The (11)B nuclear magnetic resonance spectrum also
      supports the boryl anion character. Moreover, the compound behaves as an
      efficient base and nucleophile in its reactions with electrophiles such as water,
      methyl trifluoromethanesulfonate, 1-chlorobutane, and benzaldehyde.

PMID- 17023657
TI  - Large punctuational contribution of speciation to evolutionary divergence at the
      molecular level.
AB  - A long-standing debate in evolutionary biology concerns whether species diverge
      gradually through time or by punctuational episodes at the time of speciation. We
      found that approximately 22% of substitutional changes at the DNA level can be
      attributed to punctuational evolution, and the remainder accumulates from
      background gradual divergence. Punctuational effects occur at more than twice the
      rate in plants and fungi than in animals, but the proportion of total divergence
      attributable to punctuational change does not vary among these groups.
      Punctuational changes cause departures from a clock-like tempo of evolution,
      suggesting that they should be accounted for in deriving dates from phylogenies.
      Punctuational episodes of evolution may play a larger role in promoting
      evolutionary divergence than has previously been appreciated.

PMID- 17023658
TI  - Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium
      entry.
AB  - TFII-I is a transcription factor and a target of phosphorylation by Bruton's
      tyrosine kinase. In humans, deletions spanning the TFII-I locus are associated
      with a cognitive defect, the Williams-Beuren cognitive profile. We report an
      unanticipated role of TFII-I outside the nucleus as a negative regulator of
      agonist-induced calcium entry (ACE) that suppresses surface accumulation of TRPC3
      (transient receptor potential C3) channels. Inhibition of ACE by TFII-I requires
      phosphotyrosine residues that engage the SH2 (Src-homology 2) domains of
      phospholipase C-g (PLC-g) and an interrupted, pleckstrin homology (PH)-like
      domain that binds the split PH domain of PLC-g. Our observations suggest a model
      in which TFII-I suppresses ACE by competing with TRPC3 for binding to PLC-g.

PMID- 17023659
TI  - Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral
      sclerosis.
AB  - Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of
      frontotemporal lobar degeneration with ubiquitin-positive inclusions and
      amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein
      specific to either disorder was unknown, we showed that TDP-43 is the major
      disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated,
      ubiquitinated, and cleaved to generate C-terminal fragments and was recovered
      only from affected central nervous system regions, including hippocampus,
      neocortex, and spinal cord. TDP-43 represents the common pathologic substrate
      linking these neurodegenerative disorders.

PMID- 17023660
TI  - Infectious prions in the saliva and blood of deer with chronic wasting disease.
AB  - A critical concern in the transmission of prion diseases, including chronic
      wasting disease (CWD) of cervids, is the potential presence of prions in body
      fluids. To address this issue directly, we exposed cohorts of CWD-naive deer to
      saliva, blood, or urine and feces from CWD-positive deer. We found infectious
      prions capable of transmitting CWD in saliva (by the oral route) and in blood (by
      transfusion). The results help to explain the facile transmission of CWD among
      cervids and prompt caution concerning contact with body fluids in prion
      infections.

PMID- 17023661
TI  - Modulation of cell adhesion and motility in the immune system by Myo1f.
AB  - Although class I myosins are known to play a wide range of roles, the
      physiological function of long-tailed class I myosins in vertebrates remains
      elusive. We demonstrated that one of these proteins, Myo1f, is expressed
      predominantly in the mammalian immune system. Cells from Myo1f-deficient mice
      exhibited abnormally increased adhesion and reduced motility, resulting from
      augmented exocytosis of beta2 integrin-containing granules. Also, the cortical
      actin that co-localizes with Myo1f was reduced in Myo1f-deficient cells. In vivo,
      Myo1f-deficient mice showed increased susceptibility to infection by Listeria
      monocytogenes and an impaired neutrophil response. Thus, Myo1f directs immune
      cell motility and innate host defense against infection.

PMID- 17023662
TI  - Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior.
AB  - A common single-nucleotide polymorphism in the brain-derived neurotrophic factor
      (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66
      (Val66Met), is associated with alterations in brain anatomy and memory, but its
      relevance to clinical disorders is unclear. We generated a variant BDNF mouse
      (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the
      variant allele. BDNF(Met) was expressed in brain at normal levels, but its
      secretion from neurons was defective. When placed in stressful settings,
      BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not
      normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key
      role in genetic predispositions to anxiety and depressive disorders.

PMID- 17023663
TI  - Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in
      dendrites.
AB  - Mammalian target of rapamycin (mTOR) is implicated in synaptic plasticity and
      local translation in dendrites. We found that the mTOR inhibitor, rapamycin,
      increased the Kv1.1 voltage-gated potassium channel protein in hippocampal
      neurons and promoted Kv1.1 surface expression on dendrites without altering its
      axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites.
      Using Kv1.1 fused to the photoconvertible fluorescence protein Kaede as a
      reporter for local synthesis, we observed Kv1.1 synthesis in dendrites upon
      inhibition of mTOR or the N-methyl-d-aspartate (NMDA) glutamate receptor. Thus,
      synaptic excitation may cause local suppression of dendritic Kv1 channels by
      reducing their local synthesis.

PMID- 17023664
TI  - Sequential growth of fetal sheep cardiac myocytes in response to simultaneous
      arterial and venous hypertension.
AB  - While the fetal heart grows by myocyte enlargement and proliferation, myocytes
      lose their capacity for proliferation in the perinatal period after terminal
      differentiation. The relationship between myocyte enlargement, proliferation, and
      terminal differentiation has not been studied under conditions of combined
      arterial and venous hypertension, as occurs in some clinical conditions. We
      hypothesize that fetal arterial and venous hypertension initially leads to
      cardiomyocyte proliferation, followed by myocyte enlargement. Two groups of fetal
      sheep received intravascular plasma infusions for 4 or 8 days (from 130 days
      gestation) to increase vascular pressures. Fetal hearts were arrested in diastole
      and dissociated. Myocyte size, terminal differentiation (%binucleation), and cell
      cycle activity (Ki-67[+] cells as a % of mononucleated myocytes) were measured.
      We found that chronic plasma infusion greatly increased venous and arterial
      pressures. Heart (but not body) weights were approximately 30% greater in
      hypertensive fetuses than controls. The incidence of cell cycle activity doubled
      in hypertensive fetuses compared with controls. After 4 days of hypertension,
      myocytes were (approximately 11%) longer, but only after 8 days were they wider
      (approximately 12%). After 8 days, %binucleation was approximately 50% greater in
      hypertensive fetuses. We observed two phases of cardiomyocyte growth and
      maturation in response to fetal arterial and venous hypertension. In the early
      phase, the incidence of cell cycle activity increased and myocytes elongated. In
      the later phase, the incidence of cell cycle activity remained elevated,
      %binucleation increased, and cross sections were greater. This study highlights
      unique fetal adaptations of the myocardium and the importance of experimental
      duration when interpreting fetal cardiac growth data.

PMID- 17023665
TI  - The parathyroid hormone family of peptides: structure, tissue distribution,
      regulation, and potential functional roles in calcium and phosphate balance in
      fish.
AB  - Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two factors that
      share amino acid sequence homology and act via a common receptor. In tetrapods,
      PTH is the main endocrine factor acting in bone and kidney to regulate calcium
      and phosphate. PTHrP is an essential paracrine developmental factor present in
      many tissues and is involved in the regulation of ossification, mammary gland
      development, muscle relaxation, and other functions. Fish apparently lack an
      equivalent of the parathyroid gland and were long thought to be devoid of PTH.
      Only in recent years has the existence of PTH-like peptides and their receptors
      in fish been firmly established. Two forms of PTH, two of PTHrP, and a protein
      with intermediate characteristics designated PTH-L are encoded by separate genes
      in teleost fish. Three receptors encoded by separate genes in fish mediate
      PTH/PTHrP actions, whereas only two receptors have so far been found in
      terrestrial vertebrates. PTHrP has been more intensively studied than PTH, from
      lampreys to advanced teleosts. It is expressed in many tissues and is present in
      high concentration in fish blood. Administration of this peptide alters calcium
      metabolism and has marked effects on associated gene expression and enzyme
      activity in vivo and in vitro. This review provides a comprehensive overview of
      the physiological roles, distribution, and molecular relationships of the piscine
      PTH-like peptides.

PMID- 17023666
TI  - Placental restriction of fetal growth reduces size at birth and alters postnatal
      growth, feeding activity, and adiposity in the young lamb.
AB  - Intrauterine growth restriction (IUGR) is associated with accelerated growth
      after birth. Together, IUGR and accelerated growth after birth predict reduced
      lean tissue mass and increased obesity in later life. Although placental
      insufficiency is a major cause of IUGR, whether it alters growth and adiposity in
      early postnatal life is not known. We hypothesized that placental restriction
      (PR) in the sheep would reduce size at birth and increase postnatal growth rate,
      fat mass, and feeding activity in the young lamb. PR reduced survival rate and
      size at birth, with soft tissues reduced to a greater extent than skeletal
      tissues and relative sparing of head width (P < 0.05 for all). PR did not alter
      absolute growth rates (i.e., the slope of the line of best fit for age vs.
      parameter size from birth to 45 days of age) but increased neonatal fractional
      growth rates (absolute growth rate relative to size at birth) for body weight
      (+24%), tibia (+15%) and metatarsal (+18%) lengths, hindlimb (+23%) and abdominal
      (+19%) circumferences, and fractional growth rates for current weight (P < 0.05)
      weekly throughout the first 45 days of life. PR and small size at birth reduced
      individual skeletal muscle weights and increased visceral adiposity in absolute
      and relative terms. PR also altered feeding activity, which increased with
      decreasing size at birth and was predictive of increased postnatal growth and
      adiposity. In conclusion, PR reduced size at birth and induced catch-up growth
      postnatally, normalizing weight and length but increasing adiposity in early
      postnatal life. Increased feeding activity may contribute to these alterations in
      growth and body composition following prenatal restraint and, if they persist,
      may lead to adverse metabolic and cardiovascular outcomes in later life.

PMID- 17023667
TI  - Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in
      diastolic heart failure: Beneficial effects of mineralocorticoid receptor
      blocker.
AB  - Cardiac aldosterone levels have not been evaluated in diastolic heart failure
      (DHF), and its roles in this type of heart failure remain unclear. This study
      aimed to detect cardiac aldosterone by use of a liquid chromatographic-mass
      spectrometric method and to assess the effects of mineralocorticoid receptor
      blockade on hypertensive DHF. Dahl salt-sensitive rats fed 8% NaCl diet from 7 wk
      (hypertensive DHF model) were divided at 13 wk into three groups: those treated
      with subdepressor doses of eplerenone (12.5 or 40 mg x kg(-1) x day(-1)) and an
      untreated group. Dahl salt-sensitive rats fed 0.3% NaCl diet served as controls.
      Cardiac aldosterone was detected in the DHF rats but not in the control rats,
      with increased ventricular levels of mineralocorticoid receptor. Cardiac levels
      of 11-deoxycorticosterone, corticosterone, and 11-dehydrocorticosterone were not
      different between the control and DHF rats, but the tissue level of
      corticosterone that has an affinity to mineralocorticoid receptor was 1,000 times
      as high as that of aldosterone. Aldosterone synthase activity and CYP11B2 mRNA
      were undetectable in the ventricular tissue of the DHF rats. Administration of
      eplerenone attenuated ventricular hypertrophy, ventricular fibrosis, myocardial
      stiffening, and relaxation abnormality, leading to the prevention of overt DHF.
      In summary, the myocardial aldosterone level increased in the DHF rats. However,
      its value was extremely low compared with corticosterone, and no evidence for
      enhancement of intrinsic myocardial aldosterone production was found. The
      upregulation of mineralocorticoid receptor may play a central role in the
      pathogenesis of DHF, and blockade of mineralocorticoid receptor is likely an
      effective therapeutic regimen of DHF.

PMID- 17023668
TI  - Naturally occurring hypertension in New World nonhuman primates: Potential role
      of the perifornical hypothalamus.
AB  - Hypertension is a prominent underlying factor in the genesis of cardiovascular
      related morbidity and mortality. A major impediment to the investigation into the
      causes of the disease is the paucity of naturally occurring animal models of the
      disease. There is evidence that some species of New World primates spontaneously
      become hypertensive. We used chronically implanted pressure transducers to assess
      normally occurring blood pressure and heart rate levels at rest and during
      routine laboratory procedures in a group of one of these New World primates
      (Aotus sp.). Resting mean arterial pressure ranged from 72 to 130 mmHg. Three
      animals were judged to have resting mean arterial pressure levels in the
      hypertensive range (> or =110 mmHg). In all of the animals, pressor responses to
      routine laboratory events were exaggerated (average highest mean pressure during
      1 min from any session was 97-196 mmHg). Subsequently, the region of the
      perifornical/lateral hypothalamus known to produce elevated blood pressure and
      heart rate responses to electrical stimulation was removed, and the blood
      pressure responses to the laboratory routines were significantly decreased and,
      in some cases, eliminated. Control lesions in nearby tissue had no effect on
      these responses. This region may play a critical role in initiating or
      exacerbating cardiovascular responses that contribute to the development of
      essential hypertension.

PMID- 17023669
TI  - Discoordinate regulation of renal nitric oxide synthase isoforms in
      ovariectomized mRen2. Lewis rats.
AB  - Estrogen depletion markedly exacerbates hypertension in female congenic mRen2.
      Lewis rats, a model of tissue renin overexpression. Because estrogen influences
      nitric oxide synthase (NOS) and NO may exert differential effects on blood
      pressure, the present study investigated the functional expression of NOS
      isoforms in the kidney of ovariectomized (OVX) mRen2. Lewis rats. OVX-mRen2.
      Lewis exhibited an increase in systolic blood pressure (SBP) of 171 +/- 5 vs. 141
      +/- 7 mmHg (P < 0.01) for intact littermates. Renal cortical mRNA and protein
      levels for endothelial NOS (eNOS) were reduced 50-60% (P < 0.05) and negatively
      correlated with blood pressure. In contrast, cortical neuronal NOS (nNOS) mRNA
      and protein levels increased 100 to 300% (P < 0.05). In the OVX kidney, nNOS
      immunostaining was more evident in the macula densa, cortical tubules, and the
      medullary collecting ducts compared with the intact group. To determine whether
      the increase in renal nNOS expression constitutes a compensatory response to the
      reduction in renal eNOS, we treated both intact and OVX mRen2. Lewis rats with
      the selective nNOS inhibitor L-VNIO from 11 to 15 wk of age. The nNOS inhibitor
      reduced blood pressure in the OVX group (185 +/- 3 vs. 151 +/- 8 mmHg, P < 0.05),
      but pressure was not altered in the intact group (146 +/- 4 vs. 151 +/- 4 mmHg).
      In summary, exacerbation of blood pressure in the OVX mRen2. Lewis rats was
      associated with the discoordinate regulation of renal NOS isoforms. Estrogen
      sensitivity in this congenic strain may involve the influence of NO through the
      regulation of both eNOS and nNOS.

PMID- 17023671
TI  - Iomazenil-single-photon emission computed tomography reveals selective neuronal
      loss in magnetic resonance-defined mismatch areas.
AB  - BACKGROUND AND PURPOSE: The mismatch of hypoperfused tissue on perfusion imaging
      and ischemic tissue on diffusion-weighted imaging is used as a surrogate marker
      for thrombolytic therapy in the extended time window. Mismatch tissue may recover
      completely, progress toward infarction, or proceed toward incomplete infarction
      with selective loss of cortical neurons. We used [(123)I]iomazenil-single-photon
      emission computed tomography (IMZ-SPECT) to characterize the neuronal integrity
      of reperfused "tissue at risk of infarction" that appeared morphologically intact
      on follow-up magnetic resonance imaging (MRI). METHODS: Twelve patients with
      acute stroke with striatocapsular (SC) infarctions were examined with multimodal
      MRI at days 0, 1, and 7; IMZ-SPECT was performed at days 5 to 15. The PI at day
      0, fluid-attenuated inversion recovery (FLAIR) image at day 7, and IMZ-SPECT were
      coregistered and stereotactically normalized. The mismatch volume of interest
      (VOI) was defined as the initial PI lesion subtracted by the FLAIR lesion at day
      7. An asymmetry ratio (AR) was computed by dividing the mean IMZ uptake of the
      mismatch VOI by the unaffected mirror VOI. The same AR was computed for signal
      intensity on FLAIR images at day 7. Three patients with cortical infarctions were
      included for calibration of the AR. In this group, the VOI consisted of the FLAIR
      lesion at day 7. RESULTS: All patients with SC infarctions had a large mismatch
      of initially hypoperfused (112+/-31 mL; mean+/-SD) and finally infarcted tissue
      (19+/-14 mL). Mean AR of cortical IMZ uptake was 0.85+/-0.01 in cortical
      infarctions and 0.95+/-0.03 in SC infarctions; thereby AR showed a continuous
      distribution from clearly reduced (0.89) to normal (1.01) in SC infarctions. Mean
      AR for FLAIR signal intensity was 1.84+/-0.14 for cortical infarctions and normal
      (1.01+0.03) for SC infarctions. CONCLUSIONS: IMZ-SPECT detected a selective loss
      of cortical neurons in patients with SC infarctions in transient hypoperfused
      tissue, which was morphologically intact on MRI.

PMID- 17023670
TI  - Leptin antagonist reveals that the normalization of caloric intake and the
      thermic effect of food after high-fat feeding are leptin dependent.
AB  - High-fat (HF) feeding induces a transient increase in caloric intake and enhances
      energy expenditure. We hypothesized that leptin is necessary for homeostatic
      restoration of the HF-enhanced caloric intake and may mediate the increase in
      uncoupling protein-1 (UCP1) in brown adipose tissue (BAT). We employed a leptin
      antagonist to examine the role of leptin in these biological processes.
      Simultaneous central administration of leptin and increasing doses of the leptin
      antagonist revealed a dose-dependent inhibition of leptin-induced hypothalamic
      signal transducer and activator of transcription-3 phosphorylation, and 7 days of
      infusion of the leptin antagonist produced the predicted increase in food intake
      and weight gain. When delivered with exogenous leptin in a 7-day infusion, the
      leptin antagonist blocked leptin-mediated anorexic effects as well as the
      increase in BAT UCP1 protein and signal transducer and activator of transcription
      3 phosphorylation. Rats were then fed an HF diet (60% kcal as fat) or chow and
      simultaneously infused with antagonist (25 microg/day into the lateral ventricle)
      for 7 days and compared with vehicle-infused chow-fed rats. Daily caloric intake
      of both HF groups peaked on day 2. HF feeding elevated caloric intake, which
      nearly normalized by day 7, whereas in the presence of the antagonist, caloric
      intake remained elevated. Moreover, the HF-mediated augmentation in UCP1 in BAT
      was prevented by the antagonist. These results demonstrate that leptin is
      essential for the homeostatic restoration of caloric intake after HF feeding and
      that this leptin antagonist is able to block central leptin signaling and leptin
      mediated UCP1 elevation.

PMID- 17023672
TI  - TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the
      Rotterdam Study.
AB  - BACKGROUND AND PURPOSE: Inflammation plays a pivotal role in the pathogenesis of
      atherosclerosis and of cardiovascular and cerebrovascular complications.
      Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with a
      central role in inflammation. Little is known of the relation of variations
      within the gene and risk of cardiovascular and cerebrovascular disease. We
      therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T,
      codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the
      risk of myocardial infarction and stroke in a population-based study. METHODS:
      Participants (N=6456) of the Rotterdam Study were included in the current study.
      Analyses of the relations of genotypes with the risk of myocardial infarction and
      stroke were performed according to Cox proportional-hazards methods. All analyses
      were adjusted for age, sex, conventional cardiovascular risk factors, and medical
      history. RESULTS: We found no association with the risk of myocardial infarction.
      A significantly increased risk of stroke was found, associated with the T allele
      of the -509 C/T polymorphism (relative risk, 1.26; (95% CI, 1.06 to 1.49) and the
      Pro variant of the codon 10 polymorphism (relative risk, 1.24; 95% CI, 1.04 to
      1.48). CONCLUSIONS: No association between the TGF-beta1 polymorphisms and
      myocardial infarction was observed; however, the -509 C/T and codon 10 Leu/Pro
      polymorphisms were associated with the risk of stroke.

PMID- 17023673
TI  - Impaired diastolic function after exchange of endogenous troponin I with C
      terminal truncated troponin I in human cardiac muscle.
AB  - The specific and selective proteolysis of cardiac troponin I (cTnI) has been
      proposed to play a key role in human ischemic myocardial disease, including
      stunning and acute pressure overload. In this study, the functional implications
      of cTnI proteolysis were investigated in human cardiac tissue for the first time.
      The predominant human cTnI degradation product (cTnI(1-192)) and full-length cTnI
      were expressed in Escherichia coli, purified, reconstituted with the other
      cardiac troponin subunits, troponin T and C, and subsequently exchanged into
      human cardiac myofibrils and permeabilized cardiomyocytes isolated from healthy
      donor hearts. Maximal isometric force and kinetic parameters were measured in
      myofibrils, using rapid solution switching, whereas force development was
      measured in single cardiomyocytes at various calcium concentrations, at sarcomere
      lengths of 1.9 and 2.2 mum, and after treatment with the catalytic subunit of
      protein kinase A (PKA) to mimic beta-adrenergic stimulation. One-dimensional gel
      electrophoresis, Western immunoblotting, and 3D imaging revealed that
      approximately 50% of endogenous cTnI had been homogeneously replaced by cTnI(1
      192) in both myofibrils and cardiomyocytes. Maximal tension was not affected,
      whereas the rates of force activation and redevelopment as well as relaxation
      kinetics were slowed down. Ca(2+) sensitivity of the contractile apparatus was
      increased in preparations containing cTnI(1-192) (pCa(50): 5.73+/-0.03 versus
      5.52+/-0.03 for cTnI(1-192) and full-length cTnI, respectively). The sarcomere
      length dependency of force development and the desensitizing effect of PKA were
      preserved in cTnI(1-192)-exchanged cardiomyocytes. These results indicate that
      degradation of cTnI in human myocardium may impair diastolic function, whereas
      systolic function is largely preserved.

PMID- 17023674
TI  - The matricellular protein CCN1 is essential for cardiac development.
AB  - The matricellular protein CCN1 (formerly named CYR61) regulates cell adhesion,
      migration, proliferation, survival, and differentiation through binding to
      integrin receptors and heparan sulfate proteoglycans. Here we show that Ccn1-null
      mice are impaired in cardiac valvuloseptal morphogenesis, resulting in severe
      atrioventricular septal defects (AVSD). Remarkably, haploinsufficiency for Ccn1
      also results in delayed formation of the ventricular septum in the embryo and
      persistent ostium primum atrial septal defects (ASD) in approximately 20% of
      adults. Mechanistically, Ccn1 is not required for epithelial-to-mesenchymal
      transformation or cell proliferation and differentiation in the endocardial
      cushion tissue. However, Ccn1 deficiency leads to precocious apoptosis in the
      atrial junction of the cushion tissue and impaired gelatinase activities in the
      muscular component of the interventricular septum at embryonic day 12.5, when
      fusion between the endocardial cushion tissue and the atrial and ventricular
      septa occurs, indicating that these defects may underlie the observed AVSD.
      Moreover, human CCN1 maps to 1p21-p31, the chromosomal location of an AVSD
      susceptibility gene. Together, these results provide evidence that deficiency in
      matrix signaling can lead to autosomal dominant AVSD, identify Ccn1(+/-) mice as
      a genetic model for ostium primum ASD, and implicate CCN1 as a candidate gene for
      AVSD in humans.

PMID- 17023675
TI  - Cellular mechanism through which parathyroid hormone-related protein induces
      proliferation in arterial smooth muscle cells: definition of an arterial smooth
      muscle PTHrP/p27kip1 pathway.
AB  - Parathyroid hormone-related protein (PTHrP) is present in vascular smooth muscle
      (VSM), is markedly upregulated in response to arterial injury, is essential for
      normal VSM proliferation, and also markedly accentuates neointima formation
      following rat carotid angioplasty. PTHrP contains a nuclear localization signal
      (NLS) through which it enters the nucleus and leads to marked increases in
      retinoblastoma protein (pRb) phosphorylation and cell cycle progression. Our goal
      was to define key cell cycle molecules upstream of pRb that mediate cell cycle
      acceleration induced by PTHrP. The cyclin D/cdk-4,-6 system and its upstream
      regulators, the inhibitory kinases (INKs), are not appreciably influenced by
      PTHrP. In striking contrast, cyclin E/cdk-2 kinase activity is markedly increased
      by PTHrP, and this is a result of a specific, marked, PTHrP-induced proteasomal
      degradation of p27(kip1). Adenoviral restoration of p27(kip1) fully reverses
      PTHrP-induced cell cycle progression, indicating that PTHrP mediates its cell
      cycle acceleration in VSM via p27(kip1). In confirmation, adenoviral delivery of
      PTHrP to murine primary vascular smooth muscle cells (VSMCs) significantly
      decreases p27(kip1) expression and accelerates cell cycle progression. p27(kip1)
      is well known to be a central cell cycle regulatory molecule involved in both
      normal and pathological VSM proliferation and is a target of widely used drug
      eluting stents. The current observations define a novel "PTHrP/p27(kip1) pathway"
      in the arterial wall and suggest that this pathway is important in normal
      arterial biology and a potential target for therapeutic manipulation of the
      arterial response to injury.

PMID- 17023677
TI  - Soluble guanylyl cyclase activation with HMR1766 attenuates platelet activation
      in diabetic rats.
AB  - OBJECTIVE: Platelet activation significantly contributes to cardiovascular
      morbidity and mortality in diabetes. An association between impaired NO-mediated
      platelet inhibition and platelet activation has recently been demonstrated in
      experimental diabetes. Guanylyl cyclase activation enhances the reduced signaling
      via the NO/cGMP pathway. We investigated whether chronic guanylyl cyclase
      activation would beneficially modulate platelet activation in experimental
      diabetes mellitus. METHODS AND RESULTS: Diabetes was induced by streptozotocin
      injection in male Wistar rats. After 2 weeks, treatment with either placebo or
      the guanylyl cyclase activator HMR1766 (10 mg/kg twice daily by gavage) was
      initiated. Two weeks later, in vivo platelet activation and in vitro platelet
      reactivity were assessed. Chronic treatment with HMR1766 enhanced NO/cGMP
      mediated signaling in platelets from diabetic rats determined by in vivo
      phosphorylation of platelet vasodilator-stimulated phosphoprotein (VASP) at
      Ser157 and Ser239. In parallel, platelet-binding of fibrinogen, surface
      expression of P-selectin, appearance of platelet-derived microparticles, and
      platelet-aggregates with other blood cells were significantly reduced by chronic
      treatment with HMR1766. CONCLUSIONS: Chronic activation of soluble guanylyl
      cyclase in diabetic rats improved markers of platelet activation and is a
      rationale approach for prevention of adverse cardiovascular events in diabetes.

PMID- 17023676
TI  - Hydrogen peroxide: a feed-forward dilator that couples myocardial metabolism to
      coronary blood flow.
AB  - OBJECTIVE: We tested the hypothesis that hydrogen peroxide (H2O2), the dismutated
      product of superoxide (O2*-), couples myocardial oxygen consumption to coronary
      blood flow. Accordingly, we measured O2*- and H2O2 production by isolated cardiac
      myocytes, determined the role of mitochondrial electron transport in the
      production of these species, and determined the vasoactive properties of the
      produced H2O2. METHODS AND RESULTS: The production of O2*- is coupled to
      oxidative metabolism because inhibition of complex I (rotenone) or III
      (antimycin) enhanced the production of O2*- during pacing by about 50% and 400%,
      respectively; whereas uncoupling oxidative phosphorylation by decreasing the
      protonmotive force with carbonylcyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP)
      decreased pacing-induced O2*- production. The inhibitor of cytosolic NAD(P)H
      oxidase assembly, apocynin, did not affect O2*- production by pacing. Aliquots of
      buffer from paced myocytes produced vasodilation of isolated arterioles (peak
      response 67+/-8% percent of maximal dilation) that was significantly reduced by
      catalase (5+/-0.5%, P<0.05) or the antagonist of Kv channels, 4-aminopyridine
      (18+/-4%, P<0.05). In intact animals, tissue concentrations of H2O2 are
      proportionate to myocardial oxygen consumption and directly correlated to
      coronary blood flow. Intracoronary infusion of catalase reduced tissue levels of
      H2O2 by 30%, and reduced coronary flow by 26%. Intracoronary administration of 4
      aminopyridine also shifted the relationship between myocardial oxygen consumption
      and coronary blood flow or coronary sinus pO2. CONCLUSIONS: Taken together, our
      results demonstrate that O2*- is produced in proportion to cardiac metabolism,
      which leads to the production of the vasoactive reactive oxygen species, H2O2.
      Our results further suggest that the production of H2O2 in proportion to
      metabolism couples coronary blood flow to myocardial oxygen consumption.

PMID- 17023678
TI  - Haemostatic factors and the risk of cardiovascular death in patients with
      coronary artery disease: the AtheroGene study.
AB  - OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery
      disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen,
      thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP)
      complexes on the risk of cardiovascular event in a prospective cohort of CAD
      patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057
      individuals with an angiographically proven coronary artery disease at baseline.
      After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular
      cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5
      hemostatic markers at baseline were associated with an increased risk of
      cardiovascular death, but not of nonfatal event. Except for vWF, these
      associations remained significant after adjustment for conventional
      cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend
      according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF,
      fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic
      markers in a stepwise Cox regression analysis where conventional risk factors and
      CRP were forced into the model, fibrinogen and D-dimers remained independently
      associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI)
      associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to
      1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with
      coronary artery disease, fibrinogen and D-dimer levels are independent predictors
      of subsequent cardiovascular death. Our data support a role of impaired
      coagulation/fibrinolysis process in the complications of coronary artery disease.

PMID- 17023679
TI  - Uncoupling of endothelial nitric oxidase synthase by hypochlorous acid: role of
      NAD(P)H oxidase-derived superoxide and peroxynitrite.
AB  - OBJECTIVE: The aim of the present study is to determine whether hypochlorous acid
      (HOCl), the major oxidant of leukocyte-derived myeloperoxidase (MPO), oxidizes
      the zinc-thiolate center of endothelial nitric oxide synthase (eNOS) and
      uncouples the enzyme. METHODS AND RESULTS: Exposure of purified recombinant eNOS
      to HOCl (> or = 100 micromol/L) released zinc and disrupted the enzyme-active
      eNOS dimers. In parallel with increased detections of both O2*- and ONOO-,
      clinically relevant concentrations of HOCl disrupted eNOS dimers in cultured
      human umbilical vein endothelial cells (HUVEC) at concentration 10- to 100-fold
      lower than those required for recombinant eNOS. In HUVEC, HOCl increased the
      translocation of both p67(phox) and p47(phox) of NAD(P)H oxidase and the
      phosphorylation of atypical protein kinase C-zeta. Further, genetic or
      pharmacological inhibition of either NAD(P)H oxidase-derived O2*- or PKC-zeta or
      NOS abolished the effects of HOCl on eNOS dimers. Consistently, HOCl increased
      both O2*- and ONOO- and eNOS dimer oxidation in isolated mouse aortas from
      C57BL/6 but less in those of gp91(phox) knock-out mice. Finally, in human carotid
      atherosclerotic arteries, eNOS predominantly existed as monomers in parallel with
      increased staining of both MPO and 3-nitrotyrosine. CONCLUSIONS: We conclude that
      HOCl uncouples eNOS by ONOO- generated from PKC-zeta-dependent NAD(P)H oxidase.

PMID- 17023680
TI  - Nitric oxide-dependent suppression of thioredoxin-interacting protein expression
      enhances thioredoxin activity.
AB  - OBJECTIVE: Cellular redox balance is regulated by enzymatic and nonenzymatic
      systems and freely diffusible nitric oxide (NO) promotes antioxidative
      mechanisms. We show the NO-dependent transcriptional regulation of the
      antioxidative thioredoxin system. METHODS AND RESULTS: Incubation of rat
      pulmonary artery smooth muscle cells (RPaSMC) with the NO donor compound S
      nitroso-glutathione (GSNO, 100 micromol/L) suppressed thioredoxin-interacting
      protein (Txnip), an inhibitor of thioredoxin function, by 71+/-18% and enhanced
      thioredoxin reductase 2.7+/-0.2 fold (n=6; both P<0.001 versus control). GSNO
      increased thioredoxin activity (1.9+/-0.5-fold after 4 hours; P<0.05 versus
      control). Promoter deletion analysis revealed that NO suppression of Txnip
      transcription is mediated by cis-regulatory elements between -1777 and -1127 bp
      upstream of the start codon. Hyperglycemia induced Txnip promoter activity (3.9+/
      0.2-fold; P<0.001) and abolished NO effects (-37.4+/-1.0% at 5.6 mmol/L glucose
      versus 12.4+/-2.1% at 22.4 mmol/L glucose; P<0.05). Immunoprecipitation
      experiments demonstrated that GSNO stimulation and mutation of thioredoxin at
      Cys69, a site of nitrosylation, had no effect on the Txnip/thioredoxin
      interaction. CONCLUSIONS: NO can regulate cellular redox state by changing
      expression of Txnip and thioredoxin reductase. This represents a novel
      antioxidative mechanism of NO independent of posttranslational protein S
      nitrosylation of thioredoxin.

PMID- 17023681
TI  - Novel platelet and vascular roles for immunoreceptor signaling.
AB  - The immunoreceptor signaling pathway has classically been defined by its role in
      mediating intracellular signals downstream of immune receptors on circulating
      cells, but recent studies have revealed new and unexpected roles for this pathway
      in vascular biology. In platelets the immunoreceptor signaling pathway is coupled
      to 2 structurally distinct platelet collagen receptors, glycoprotein VI and
      integrin alpha2beta1, and is required for the activation of platelets after
      exposure to vessel wall collagen during plaque rupture. During vascular
      development immunoreceptor signaling is required for proper formation of the
      lymphatic system, a role that has revealed the contribution of hematopoietic
      endothelial progenitors to that process. In conjunction with the identification
      of new biological roles in vascular cell types, new molecular mechanisms of
      activating this signaling pathway have been discovered, including activation by
      integrins and immunoreceptor tyrosine activation motifs (ITAMs) on receptors that
      do not function as part of the immune response. Here we discuss some of these
      recent findings and their implications for vascular biology and the treatment of
      human vascular diseases.

PMID- 17023682
TI  - Tissue factor pathway inhibitor-2 is upregulated by vascular endothelial growth
      factor and suppresses growth factor-induced proliferation of endothelial cells.
AB  - OBJECTIVE: The purpose of this study is to investigate the expression and
      regulation of type-2 tissue factor pathway inhibitor (TFPI-2) in endothelial
      cells, as well as the regulation of human endothelial cell (EC) function by TFPI
      2. METHODS AND RESULTS: Real-time polymerase chain reaction (PCR) and Western
      blot analysis revealed that vascular endothelial growth factor (VEGF) induced
      both time- and dose-dependent increase in TFPI-2 mRNA and protein expression in
      endothelial cells. TFPI-2 mRNA expression was also significantly upregulated by
      IL-1beta, and modestly increased by both tumor necrosis factor (TNF)-alpha and
      fibroblast growth factor (FGF)-2, but not placental growth factor (PlGF). VEGF
      upregulation of TFPI-2 was dramatically reduced by inhibition of the MEK pathway.
      Administration of TFPI-2 protein suppressed both VEGF and FGF-2 stimulation of EC
      proliferation in a dose-dependent manner. A recombinant preparation of the first
      Kunitz-type domain of TFPI-2 (KD1) did not suppress growth factor stimulation of
      EC proliferation, suggesting a mechanism distinct from the proteinase inhibitory
      activity of TFPI-2. Exogenously added TFPI-2 protein suppressed VEGF-induced EC
      migration in 2 different assays. Recombinant wt-KD1 or the R24K mutant of KD1,
      but not the R24Q mutant, dramatically suppressed VEGF-induced EC migration. TFPI
      2 protein, but not recombinant KD1, blocked VEGF-induced activation of both Akt
      and ERK1/2 in ECs. At higher doses, TFPI-2 protein blocked VEGFR2 activation.
      CONCLUSIONS: Our data suggest that VEGF-upregulation of TFPI-2 expression in
      endothelial cells may represent a mechanism for negative feedback regulation and
      modulation of its pro-angiogenic action on endothelial cells. TFPI-2, or
      derivatives of TFPI-2, may be novel therapeutics for treatment of angiogenic
      disease processes.

PMID- 17023683
TI  - Inflammatory response after influenza vaccination in men with and without carotid
      artery disease.
AB  - OBJECTIVE: Inflammatory markers are associated with vascular disease; however,
      variation in the acute phase response (APR) has not been evaluated. We evaluated
      whether the APR magnitude in men with severe carotid artery disease (CAAD) (>80%
      stenosis) differed from that of men without stenosis (<15% stenosis). METHODS AND
      RESULTS: White males with (n=43) and without (n=61) severe CAAD receiving
      clinical influenza vaccinations were recruited. Their baseline and 24-hour after 
      vaccination blood samples were assayed for C-reactive protein (CRP), IL-6, and
      serum amyloid-a (SAA). In vivo APR to vaccination was measurable and varied among
      subjects. Adjusted for age, smoking, oral hypoglycemics, aspirin, and stain use,
      the relative 24-hour changes in levels of ln(CRP), ln(IL-6), and ln(SAA) were
      higher in men with CAAD than in men without, but only the SAA response was
      significant (P=0.02); the relative SAA response was 1.6 (95% confidence interval,
      1.1 to 2.5) times higher in men with than without CAAD. The APR for all markers
      appeared to be independent of baseline levels. CONCLUSIONS: Influenza vaccination
      results in a mild, but measurable, APR in men with and without CAAD. SAA APR
      variability may be a predictor of severe vascular disease that is independent of
      basal SAA level.

PMID- 17023684
TI  - Involvement of the alpha2,8-polysialyltransferases II/STX and IV/PST in the
      biosynthesis of polysialic acid chains on the O-linked glycoproteins in rainbow
      trout ovary.
AB  - Polysialoglycoprotein (PSGP) in salmonid fish egg is a unique glycoprotein
      bearing alpha2,8-linked polysialic acid (polySia) on its O-linked glycans.
      Biosynthesis of the polySia chains is developmentally regulated and only occurs
      at later stage of oogenesis. Two alpha2,8-polysialyltransferases (alpha2,8
      polySTs), PST (ST8Sia IV) and STX (ST8Sia II), responsible for the biosynthesis
      of polySia on N-glycans of glycoproteins, are known in mammals. However, nothing
      has been known about which alpha2,8-polySTs are involved in the biosynthesis of
      polySia on O-linked glycans in any glycoproteins. We thus sought to identify cDNA
      encoding the alpha2,8-polyST involved in polysialylation of PSGP. A clone for PST
      orthologue, rtPST, and two clones for the STX orthologue, rtSTX-ov and rtSTX-em,
      were identified in rainbow trout. The deduced amino acid sequence of rtPST shows
      a high identity (72-77%) to other vertebrate PSTs, while that of rtSTX-ov shows
      92% identity with rtSTX-em and a significant identity (63-76%) to other
      vertebrate STXs. The rtPST exhibited the in vivo alpha2,8-polyST activity,
      although its in vitro activity was low. However, the rtSTXs showed no in vivo and
      very low in vitro activities. Interestingly, co-existence of rtPST and rSTX-ov in
      the reaction mixture synergistically enhanced the alpha2,8-polyST activity.
      During oogenesis, rtPST was constantly expressed, while the expression of rtSTX
      ov was not increased until polySia chain is abundantly biosynthesized in the
      later stage. rtSTX-em was not expressed in ovary. These results suggest that the
      enhanced expression of rtSTX-ov under the co-expression with rtPST may be
      important for the biosynthesis of polySia on O-linked glycans of PSGP.

PMID- 17023685
TI  - Effects of nucleotides on the interaction of renin with GlcNAc 2-epimerase (renin
      binding protein, RnBP).
AB  - Renin binding protein (RnBP), a cellular renin inhibitor, was identified as an
      enzyme, GlcNAc 2-epimerase. Recombinant RnBP inhibited porcine renin activity in
      a dose dependent manner. However, the inhibition was neutralized by nucleotides,
      such as ATP, dATP, dGTP, dCTP or dTTP. Moreover, ATP inhibited the formation of
      hetero-complex of renin with RnBP, called high molecular weight (HMW) renin. On
      the other hand, N-ethylmaleimide (NEM), a SH-alkylating reagent inhibited the
      GlcNAc 2-epimerase activity concomitant with the decaying of the dimer to the
      monomer of the enzyme. The inhibition was modulated in the presence of ATP. These
      results indicate that nucleotides stabilize the dimeric form RnBP (GlcNAc 2
      epimerase) and inhibited the formation of the renin-RnBP hetero complex, HMW
      renin.

PMID- 17023686
TI  - Identification of immunoglobulins that recognize 3-nitrotyrosine in patients with
      acute lung injury after major trauma.
AB  - Tyrosine nitration is a nitric oxide-derived post-translational modification of
      proteins. Elevated levels of specific plasma proteins modified by tyrosine
      nitration have been detected during acute and chronic inflammatory conditions,
      including acute lung injury (ALI). In the present study we examined whether
      circulating immunoglobulins against nitrated proteins are present in the plasma
      of subjects with clinically documented ALI. Affinity chromatography using
      covalently linked 3-nitrotyrosine was employed to identify plasma proteins that
      bind to this unusual amino acid. Western blotting and liquid chromatography
      tandem mass spectrometry of in-gel digested protein bands revealed that the major
      proteins eluted from the affinity column were IgM and IgG. An enzyme-linked
      immunosorbent assay (ELISA) based on competition of horseradish peroxidase
      derivatized 3-nitrotyrosine binding to plasma with unlabeled 3-nitrotyrosine was
      developed and validated. Using this ELISA, the levels of immunoglobulins that
      recognize 3-nitrotyrosine were significantly higher in the plasma of subjects
      with ALI compared with both normal control subjects and subjects with major
      trauma who did not develop ALI (0.36+/- 0.14 versus 0.03 +/- 0.05, and 0.25 +/-
      0.15; P < 0.001 and P = 0.006, respectively). These data indicate that tyrosine
      nitrated proteins induce the production of specific immunoglobulins during acute
      phase response and inflammation.

PMID- 17023687
TI  - Plasmacytoid dendritic cells from human lung cancer draining lymph nodes induce
      Tc1 responses.
AB  - Dendritic cells (DC) resident in draining lymph nodes (LN) of patients with lung
      cancer are proposed to have a critical role in stimulating anti-tumor immunity.
      CpG oligodeoxynucleotides are undergoing clinical trials in patients with lung
      cancer and are likely to target plasmacytoid-DC. The present study, therefore,
      investigated the capacity of plasmacytoid-DC from human lung cancer draining LN
      to respond to CpG for activation of T cell responses relevant to anti-tumor
      immunity. The phenotype of DC was examined by flow cytometry, and cytokine
      production by cytometric bead array (CBA) and ELISA. Plasmacytoid-DC, purified by
      cell sorting, were immature but expressed the toll-like receptor, TLR9.
      Plasmacytoid-DC responded to the CpG oligodeoxynucleotide, CpG 2216, by
      production of the proinflammatory cytokines, IFN-alpha and IL-6. DC were
      cocultured with normal, allogeneic T cells, and cytokine production determined by
      CBA and immunophenotyping. CpG 2216 enhanced IFN-gamma production and induced
      intracellular production of IFN-gamma by CD8(+) and CD4(+), granzyme B by CD8(+),
      and IL-2 by CD4(+) T cells, respectively. Ligation of CD40 on plasmacytoid-DC
      combined with exposure to CpG 2216 also strongly enhanced IFN-gamma production.
      There was no significant difference between the responses of plasmacytoid-DC from
      patients with lung cancer and patients with benign carcinoid tumors with no
      pathologic LN involvement. These results indicate that plasmacytoid DC from the
      draining LN of patients with lung cancer effectively induce Tc1 immunity and
      could, therefore, represent a novel and attractive target for immunotherapeutic
      intervention.

PMID- 17023688
TI  - Efficacy of IL-13 neutralization in a sheep model of experimental asthma.
AB  - IL-13 contributes to airway hyperresponsiveness, mucus secretion, inflammation,
      and fibrosis, suggesting that it plays a central role in asthma pathogenesis.
      Neutralization of IL-13 with sIL-13Ralpha2-Fc (sIL-13R) reduces allergen-induced
      airway responses in rodent models of respiratory disease, but its efficacy in a
      large animal model has not been previously reported. In this study, we determined
      whether two different strategies for IL-13 neutralization modified experimental
      asthma in sheep. Sheep with natural airway hypersensitivity to Ascaris suum
      antigen were treated intravenously either with sIL-13R, a strong antagonist of
      sheep IL-13 bioactivity in vitro, or with IMA-638 (IgG1, kappa), a humanized
      antibody to human IL-13. Higher doses of IMA-638 were used because, although it
      is a potent antagonist of human IL-13, this antibody has 20 to 30 times lower
      binding and neutralization activity against sheep IL-13. Control animals received
      human IgG of irrelevant specificity. Sheep were treated 24 h before inhalation
      challenge with nebulized A. suum. The effects on antigen-induced early and late
      bronchial responses, and antigen-induced hyperresponsiveness, were assessed. Both
      sIL-13R and IMA-638 provided dose-dependent inhibition of the antigen-induced
      late responses and airway hyperresponsiveness. The highest dose of IMA-638 also
      reduced the early phase response. These findings suggest that IL-13 contributes
      to allergen-induced airway responses in this sheep model of asthma, and that
      neutralization of IL-13 is an effective strategy for blocking these A. suum
      induced effects.

PMID- 17023689
TI  - Der p, IL-4, and TGF-beta cooperatively induce EGFR-dependent TARC expression in
      airway epithelium.
AB  - Thymus and Activation-Regulated Chemokine (TARC) may be critical in Th2 cell
      recruitment in allergic inflammation; however, the mechanisms of allergen-induced
      TARC release are unclear. Since airway epithelium is the first line of defense to
      inhaled allergens, we questioned whether house dust mite allergen (Der p) can
      induce TARC expression in bronchial epithelial cells, how this is regulated at
      the molecular level, and if micro-environmental cytokines augment this effect. We
      examined the effects of Der p and the cytokines IL-4 and TGF-beta on TARC
      expression in 16HBE cells and primary bronchial asthma epithelium. Real-time PCR
      and immunofluorescence demonstrated that Der p induces TARC expression in
      bronchial epithelium. Supernatants from Der p-stimulated 16HBE cells were able to
      induce TARC-dependent T cell trafficking. IL-4 and TGF-beta cooperatively
      enhanced Der p-induced TARC expression in 16HBE cells. Specific inhibitors,
      immunodetection, and gel-shifts revealed that these effects are mediated by
      phosphorylation of the epidermal growth factor receptor (EGFR), mitogen-activated
      protein kinase (MAPK) signaling and subsequent nuclear factor (NF)-kappaB
      activation. A Disintegrin And Metalloproteinase (ADAM), a family of proteins
      involved in shedding of various growth factors, was shown to be responsible for
      EGFR activation. The increase in TARC production by direct interaction of Der p
      with the bronchial epithelium may be an important initial step in the generation
      of allergic inflammation, which is further potentiated by micro-environmental
      cytokines. Interference with ADAM or EGFR activity may be a novel promising
      target to prevent TARC release and subsequent allergic inflammation.

PMID- 17023690
TI  - Weighing in on glycemic index and body weight.

PMID- 17023691
TI  - The dubious use of vitamin-mineral supplements in relation to cardiovascular
      disease.

PMID- 17023692
TI  - Coffee, diabetes, and weight control.
AB  - Several prospective epidemiologic studies over the past 4 y concluded that
      ingestion of caffeinated and decaffeinated coffee can reduce the risk of
      diabetes. This finding is at odds with the results of trials in humans showing
      that glucose tolerance is reduced shortly after ingestion of caffeine or
      caffeinated coffee and suggesting that coffee consumption could increase the risk
      of diabetes. This review discusses epidemiologic and laboratory studies of the
      effects of coffee and its constituents, with a focus on diabetes risk. Weight
      loss may be an explanatory factor, because one prospective epidemiologic study
      found that consumption of coffee was followed by lower diabetes risk but only in
      participants who had lost weight. A second such study found that both caffeine
      and coffee intakes were modestly and inversely associated with weight gain. It is
      possible that caffeine and other constituents of coffee, such as chlorogenic acid
      and quinides, are involved in causing weight loss. Caffeine and caffeinated
      coffee have been shown to acutely increase blood pressure and thereby to pose a
      health threat to persons with cardiovascular disease risk. One short-term study
      found that ground decaffeinated coffee did not increase blood pressure.
      Decaffeinated coffee, therefore, may be the type of coffee that can safely help
      persons decrease diabetes risk. However, the ability of decaffeinated coffee to
      achieve these effects is based on a limited number of studies, and the underlying
      biological mechanisms have yet to be elucidated.

PMID- 17023693
TI  - The case against ergocalciferol (vitamin D2) as a vitamin supplement.
AB  - Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin
      D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded
      these 2 forms as equivalent and interchangeable, yet this presumption of
      equivalence is based on studies of rickets prevention in infants conducted 70 y
      ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status
      provides an objective, quantitative measure of the biological response to vitamin
      D administration. As a result, vitamin D3 has proven to be the more potent form
      of vitamin D in all primate species, including humans. Despite an emerging body
      of evidence suggesting several plausible explanations for the greater bioefficacy
      of vitamin D3, the form of vitamin D used in major preparations of prescriptions
      in North America is vitamin D2. The case that vitamin D2 should no longer be
      considered equivalent to vitamin D3 is based on differences in their efficacy at
      raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites
      to vitamin D binding protein in plasma, and a nonphysiologic metabolism and
      shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be
      regarded as a nutrient suitable for supplementation or fortification.

PMID- 17023694
TI  - Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and
      in healthy adolescents.
AB  - BACKGROUND: Adolescence is a common time for the onset of anorexia nervosa (AN),
      a condition associated with long-term medical and hormonal consequences.
      OBJECTIVE: The objective was to compare the nutrient intakes of community
      dwelling girls with AN with those of healthy adolescents and to describe the
      associations between specific nutrient intakes and nutritionally dependent
      hormones. DESIGN: Nutrient intakes in 39 community-dwelling girls with AN and 39
      healthy adolescents aged 12.1-18.7 y were determined by using 4-d food records.
      Fasting adiponectin, leptin, ghrelin, insulin, and insulin-like growth factor I
      (IGF-I) concentrations were measured. Indirect calorimetry was used to assess
      respiratory quotient and resting energy expenditure. RESULTS: In contrast with
      the control group, the AN group consumed fewer calories from fats (P < 0.0001)
      and more from carbohydrates (P = 0.0009) and proteins (P < 0.0001). Intake of
      individual fat components was lower and of dietary fiber higher in the AN group.
      No significant between-group differences were observed in dietary intakes of
      calcium, zinc, and iron; however, total intake was greater in the AN group
      because of greater supplement use (P = 0.006, 0.02, and 0.01, respectively). The
      AN group had greater intakes of vitamins A, D, and K and of most of the B
      vitamins, and significantly more girls with AN met the Dietary Reference Intake
      for calcium (P = 0.01) and vitamin D (P = 0.02) from supplement use. Fat intake
      predicted ghrelin, insulin, and IGF-I concentrations; carbohydrate intake
      predicted adiponectin. Resting energy expenditure was lower (P < 0.0001) and
      leisure activity levels higher in the AN group. CONCLUSIONS: Despite outpatient
      follow-up, community-dwelling girls with AN continue to have lower fat and higher
      fiber intakes than do healthy adolescents, which results in lower calorie
      intakes. Nutritionally related hormones are associated with specific nutrient
      intakes.

PMID- 17023695
TI  - Are American children and adolescents of low socioeconomic status at increased
      risk of obesity? Changes in the association between overweight and family income
      between 1971 and 2002.
AB  - BACKGROUND: A good understanding of the association between obesity and
      socioeconomic status (SES) has many important public health and policies
      implications, particularly for the prevention and management of obesity.
      OBJECTIVE: The objective was to examine secular trends in the relations between
      overweight (body mass index > or = 95th percentile) and SES. DESIGN: We examined
      secular trends in the relation between overweight and SES using nationally
      representative data collected in the National Health and Nutrition Examination
      Surveys (NHANES) between 1971 and 2002 for 30 417 US children aged 2-18 y.
      Poverty income ratio tertiles at each survey were used to indicate low, middle,
      and high SES. RESULTS: Considerable race, sex, and age differences were observed
      in the association between overweight and SES. A reverse association only existed
      in white girls; African American children with a high SES were at increased risk.
      Socioeconomic disparities in overweight have changed over time, with an overall
      trend of weakening. Compared with the medium-SES group, the adjusted odds ratios
      and 95% CIs were 0.79 (0.47, 1.33), 1.08 (0.73, 1.61), 1.24 (0.73, 2.09), and
      1.04 (0.82, 1.33) in NHANES I, II, and III and in the 1999-2002 NHANES for the
      low-SES group and 0.66 (0.43, 1.00), 0.60 (0.35, 1.03), 0.42 (0.23, 0.76), and
      0.99 (0.68, 1.43) for the high-SES group, respectively. Between 1988-1994 and
      1999-2002, the ratio in the prevalence of overweight between adolescent boys with
      a low or high SES decreased from 2.5 to 1.1 and from 3.1 to 1.6 in girls.
      Consistently across almost all SES groups, the prevalence of overweight was much
      higher in blacks than in whites. CONCLUSIONS: Complex patterns in the association
      between SES and overweight exist. Efforts solely targeting reductions in income
      disparities probably cannot effectively reduce racial disparities in obesity.

PMID- 17023696
TI  - Determinants of overweight in a cohort of Dutch children.
AB  - BACKGROUND: To improve the effective prevention and treatment of obesity, it is
      important to focus on body weight (BW) development and its determinants during
      childhood. OBJECTIVE: The aim of the present study was to investigate the effects
      of early development, parental and genetic variables, and behavioral determinants
      on overweight at 12 y. DESIGN: In a Dutch cohort of 105 children, anthropometric
      measurements were conducted from birth until age 7 y. At age 12 y, anthropometric
      measurements were obtained again, as were measurements of body composition,
      leptin concentration, 3 polymorphisms, and physical activity, and the Three
      Factor Eating Questionnaire was conducted. In addition, parental body mass
      indexes (BMIs, in kg/m2) and Three-Factor Eating Questionnaire scores were
      determined. RESULTS: The children's mean (+/-SD) BMI at 12 y was 19.0 +/- 2.6,
      and 15.2% were classified as overweight. From the first year of life, BMI tracked
      significantly with BMI at age 12 y (r = 0.24, P < 0.05). Linear regression
      analyses showed that a rapid increase in BW during the first year of life, a high
      BMI of the father, and a high dietary restraint score of the mother were
      significantly associated with overweight at age 12 y (P < 0.05). No significant
      genetic relation was observed. In addition, overweight was positively associated
      with dietary restraint of the child, and percentage body fat was negatively
      associated with the child's activity score (P < 0.05). CONCLUSIONS: In this
      homogeneous cohort of normal-weight to moderately overweight children, tracking
      of BMI during childhood took place from the first year of life. Overweight at age
      12 y was predicted by an early rapid increase in BW and parental influences.
      Overweight during childhood may be maintained or even promoted by a high dietary
      restraint score and low physical activity.

PMID- 17023697
TI  - Less activation of the left dorsolateral prefrontal cortex in response to a meal:
      a feature of obesity.
AB  - BACKGROUND: In an exploratory positron emission tomography study of postprandial
      regional cerebral blood flow, which is a marker of neuronal activity, obese men
      differed from lean men in several brain regions, including the prefrontal cortex.
      The subjects received a meal proportional to their body size; therefore, the meal
      volume was different for each person. OBJECTIVE: We investigated whether
      differences in the brain responses of obese and lean men to a meal represent
      satiety or feelings of gastric distension. DESIGN: We studied 9 lean (x +/- SD
      body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32
      +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their
      results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese
      (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal
      proportional to their body size. We performed analyses by using a two-level,
      random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package
      and a significance level of P < or = 0.001, uncorrected for multiple comparisons.
      RESULTS: Compared with lean men, obese men had consistently less postprandial
      activation in the left dorsolateral prefrontal cortex, irrespective of meal size.
      CONCLUSION: Because the dorsolateral prefrontal cortex has been implicated in the
      inhibition of inappropriate behavior, satiety, and meal termination, differential
      responses of neuronal activity to food intake in this area may contribute to a
      propensity for obesity or to the difficulty in losing weight experienced by obese
      men.

PMID- 17023698
TI  - Effects of binge eating on satiation, satiety, and energy intake of overweight
      children.
AB  - BACKGROUND: Children who report episodes of binge eating gain more weight than do
      children not reporting binge eating. However, how binge eating affects children's
      food intake at meals is unknown. OBJECTIVE: We compared the energy intake and
      postmeal satiety of children with and without a history of binge eating during
      buffet meals. DESIGN: Sixty overweight children aged 6-12 y were categorized into
      those reporting past binge-eating episodes (n = 10) and those reporting no such
      episodes (n = 50). Children selected lunch twice from a multiple-item, 9835 kcal,
      buffet meal: after an overnight fast and after a standardized breakfast. Children
      ate ad libitum, until they reported they were full. The main outcome measures
      were energy intake during meals and duration of postmeal satiety, after
      adjustment for covariates, including age, race, sex, socioeconomic status, and
      body composition. RESULTS: After the overnight fast, children in the binge-eating
      group consumed more energy [x (+/-SD): 1748 +/- 581 compared with 1309 +/- 595
      kcal; P = 0.04] and exhibited a shorter satiety duration (194 +/- 84 compared
      with 262 +/- 89 min; P = 0.03) than did children in the non-binge-eating group.
      After the standardized breakfast, binge-eating children reported a shorter
      satiety duration (75 +/- 62 compared with 132 +/- 62 min; P = 0.01) and consumed
      more energy at the postbreakfast meal (1874 +/- 560 compared with 1275 +/- 566
      kcal; P = 0.004). CONCLUSION: The ability to consume large quantities of
      palatable foods, coupled with decreased subsequent satiety, may play a role in
      the greater weight gain found in binge-eating children.

PMID- 17023699
TI  - Associations of size at birth and dual-energy X-ray absorptiometry measures of
      lean and fat mass at 9 to 10 y of age.
AB  - BACKGROUND: Birth weight has been positively associated with risk of overweight
      in later life. However, little information exists on how weight and length at
      birth are associated with subsequent lean and total body fat. OBJECTIVE: We
      investigated the association between weight and length at birth and body
      composition and fat distribution in childhood. DESIGN: Body composition was
      measured by using dual-energy X-ray absorptiometry in 9-10-y-old subjects (n =
      3006 boys and 3080 girls). Weight and length at birth were measured or taken from
      hospital records. RESULTS: Birth weight was positively associated with both lean
      body mass (LBM) and total body fat at 9-10 y of age in both sexes. LBM rose by
      320 g per 1-SD increase in birth weight (P < 0.001), and total body fat rose by
      2.5% (P = 0.001), but birth weight was unassociated with the fat-to-lean mass
      ratio (FLR). Ponderal index (PI) at birth (ie, weight/length3) was positively
      associated with LBM, total body fat, and the FLR in both sexes; the FLR increased
      by 2.7% in boys (P = 0.021) and by 5.0% in girls per 1-SD increase in PI (P <
      0.001). Weight and length at birth did not predict central adiposity; although
      trunk fat had a strong positive association with PI at birth, this association
      disappeared after adjustment for total body fat. CONCLUSIONS: Higher PI at birth
      is associated with both higher fat and lean mass in childhood but also with an
      increase in the FLR. PI at birth is a better predictor of subsequent adiposity
      than is birth weight.

PMID- 17023700
TI  - Dietary intakes of fat and antioxidant vitamins are predictors of subclinical
      inflammation in overweight Swiss children.
AB  - BACKGROUND: In obese children, subclinical inflammation is often present and is
      correlated with the metabolic syndrome. Dietary factors, such as fatty acids and
      antioxidants, potentially modulate the association between adiposity and
      subclinical inflammation, but few data are available in children. OBJECTIVE: The
      aim of the study was to determine whether dietary fat or antioxidant intakes
      influence circulating tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL
      6), C-reactive protein (CRP), and leptin concentrations in overweight children.
      DESIGN: In a cross-sectional study of 6-14-y-old normal-weight (n = 33),
      overweight (n = 19), and obese (n = 27) Swiss children, nutritional intakes were
      assessed from two 24-h dietary recalls and a 1-d dietary record. Percentage body
      fat from skinfold thicknesses, waist-hip ratio, and blood pressure were measured.
      Fasting blood samples were collected for the measurement of insulin, glucose, HDL
      cholesterol, triacylglycerol, CRP, IL-6, TNF-alpha, and leptin concentrations.
      RESULTS: CRP, IL-6, and leptin increased significantly (P < 0.02) with increasing
      adiposity, independent of age; TNF-alpha did not increase. Total dietary fat and
      the percentage of energy from fat were significant predictors of CRP
      concentration, independent of body mass index (P < 0.05). Meat intake was a
      significant predictor of IL-6 and leptin, independent of body mass index (P <
      0.05). Intakes of antioxidant vitamins (vitamins E and C and beta-carotene) were
      significant predictors of leptin (P < 0.05) but not of CRP, IL-6, or TNF-alpha.
      CONCLUSIONS: Overweight Swiss children as young as 6 y have elevated
      concentrations of inflammatory markers. Intakes of total fat and antioxidant
      vitamins are determinants of subclinical inflammation in this age group.

PMID- 17023701
TI  - Reduced-calorie orange juice beverage with plant sterols lowers C-reactive
      protein concentrations and improves the lipid profile in human volunteers.
AB  - BACKGROUND: Dietary plant sterols effectively reduce LDL cholesterol when
      incorporated into fat matrices. We showed previously that supplementation with
      orange juice containing plant sterols (2 g/d) significantly reduced LDL
      cholesterol. Inflammation is pivotal in atherosclerosis. High-sensitivity C
      reactive protein (hs-CRP), the prototypic marker of inflammation, is a
      cardiovascular disease risk marker; however, there is a paucity of data on the
      effect of plant sterols on CRP concentrations. OBJECTIVE: The aim of this study
      was to examine whether plant sterols affect CRP concentrations and the
      lipoprotein profile when incorporated into a reduced-calorie (50 calories/240 mL)
      orange juice beverage. DESIGN: Seventy-two healthy subjects were randomly
      assigned to receive a reduced-calorie orange juice beverage either without
      (Placebo Bev) or with (1 g/240 mL; Sterol Bev) plant sterols twice a day with
      meals for 8 wk. Fasting blood was obtained at baseline and after 8 wk of Placebo
      Bev or Sterol Bev supplementation. RESULTS: Sterol Bev supplementation
      significantly reduced total cholesterol (5%; P < 0.01) and LDL cholesterol (9.4%;
      P < 0.001) compared with both baseline and Placebo Bev (P < 0.05). HDL
      cholesterol increased significantly with Sterol Bev (P < 0.02). No significant
      changes in triacylglycerol, glucose, or liver function tests were observed with
      Sterol Bev. Sterol Bev supplementation resulted in no significant change in
      vitamin E and carotenoid concentrations. Sterol Bev supplementation resulted in a
      significant reduction of CRP concentrations compared with baseline and Placebo
      Bev (median reduction: 12%; P < 0.005). CONCLUSION: Supplementation with a
      reduced-calorie orange juice beverage containing plant sterols is effective in
      reducing CRP and LDL cholesterol and could be incorporated into the dietary
      portion of therapeutic lifestyle changes.

PMID- 17023702
TI  - Selenium and coronary heart disease: a meta-analysis.
AB  - BACKGROUND: It is hypothesized that low selenium concentrations are associated
      with an increased risk of cardiovascular disease and that selenium supplements
      prevent coronary heart disease. OBJECTIVE: The objective was to perform a meta
      analysis on the association of selenium biomarkers with coronary heart disease
      endpoints in observational studies and on the efficacy of selenium supplements in
      preventing coronary heart disease endpoints in randomized trials. DESIGN: The
      MEDLINE and the Cochrane Library databases were searched for studies conducted
      from 1966 through 2005. Relative risks were pooled by using an inverse-variance
      weighted random-effects model. RESULTS: Twenty-five observational studies (14
      cohort and 11 case-control studies) that measured blood or toenail selenium
      concentrations and 6 randomized trials that evaluated supplements containing
      selenium met our inclusion criteria. The pooled relative risk in a comparison of
      the highest with the lowest selenium concentration categories was 0.85 (95% CI:
      0.74, 0.99) in cohort studies and 0.43 (0.29, 0.66) in case-control studies. In
      observational studies, a 50% increase in selenium concentrations was associated
      with a 24% (7%, 38%) reduction in coronary heart disease risk. In randomized
      trials, the pooled relative risk in a comparison of supplements containing
      selenium with placebo was 0.89 (0.68, 1.17). CONCLUSIONS: Selenium concentrations
      were inversely associated with coronary heart disease risk in observational
      studies. Because observational studies have provided misleading evidence for
      other antioxidants, the validity of this association is uncertain. Few randomized
      trials have addressed the cardiovascular efficacy of selenium supplementation,
      and their findings are still inconclusive. Evidence from large ongoing trials is
      needed to establish low selenium concentrations as a cardiovascular disease risk
      factor. Currently, selenium supplements should not be recommended for
      cardiovascular disease prevention.

PMID- 17023703
TI  - Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and
      iron status in postmenopausal women.
AB  - BACKGROUND: Soy protein or its components may protect against the atherosclerotic
      cardiovascular disease (CVD) risk factors total homocysteine (tHcy), C-reactive
      protein (CRP), and excess body iron, which generally increase with menopause.
      OBJECTIVE: The primary objective of this study was to determine the independent
      effect of the soy protein components isoflavones and phytate on CVD risk factors
      in postmenopausal women. The secondary objective was to identify factors [blood
      lipids, oxidative stress indexes, serum ferritin, plasma folate, plasma vitamin B
      12, and body mass index (BMI)] contributing to tHcy and CRP concentrations.
      DESIGN: In a double-blind, 6-wk study, 55 postmenopausal women aged 47-72 y were
      randomly assigned to 1 of 4 soy protein (40 g/d) isolate treatments: native
      phytate and native isoflavone (n = 14), native phytate and low isoflavone (n =
      13), low phytate and native isoflavone (n = 14), or low phytate and low
      isoflavone (n = 14). We measured iron indexes, tHcy, CRP, and BMI. RESULTS: Soy
      protein with native phytate significantly reduced tHcy (P = 0.017), transferrin
      saturation (P = 0.027), and ferritin (P = 0.029), whereas soy protein with native
      isoflavones had no effect on any variables. At baseline, BMI was highly
      correlated with tHcy (r = 0.39, P = 0.003) and CRP (r = 0.55, P < 0.0001),
      whereas HDL cholesterol was correlated with CRP (r = -0.30, P = 0.02). Multiple
      regression analysis showed that LDL cholesterol and BMI contributed significantly
      (R2= 19.9%, P = 0.003) to the overall variance in tHcy. CONCLUSION: Consuming
      phytate-rich foods and maintaining a healthy weight may reduce atherosclerotic
      CVD risk factors in postmenopausal women.

PMID- 17023705
TI  - Intake of macronutrients as predictors of 5-y changes in waist circumference.
AB  - BACKGROUND: The diet may influence the development of abdominal obesity, but the
      few studies that have prospectively examined the relations between diet and
      changes in waist circumference (WC) have given inconsistent results. OBJECTIVE:
      Associations between total energy intake, energy intake from macronutrients, and
      energy intake from macronutrient subgroups based on different food sources and 5
      y differences in WC (DWC) were investigated. DESIGN: A Danish cohort of 22 570
      women and 20 126 men aged 50-64 y with baseline data on WC, diet, BMI, and
      potential confounders reported their WC 5 y later. Associations of baseline diet
      with DWC were assessed by multiple linear regression analysis. RESULTS: Neither
      total energy intake nor energy intake from each of the macronutrients was
      associated with DWC, except for an inverse association with protein, especially
      animal protein. In women, positive associations with DWC were seen for
      carbohydrate from refined grains and potatoes and from foods with simple sugars,
      whereas carbohydrate from fruit and vegetables was inversely associated and
      significantly different from any other carbohydrate subgroup. The results for men
      resembled those for women, although none were significant. Vegetable fat was
      positively associated with DWC for both men and women in a combined analysis. A U
      shaped association between alcohol from wine and DWC was present for both sexes,
      and alcohol from spirits was positively associated with DWC in women.
      CONCLUSIONS: Although no significant associations with total energy or energy
      from fat, carbohydrate, or alcohol were observed, protein intake was inversely
      related to DWC, and some macronutrient subgroups were significantly associated
      with DWC.

PMID- 17023704
TI  - Asymmetrical dimethylarginine regulates endothelial function in methionine
      induced but not in chronic homocystinemia in humans: effect of oxidative stress
      and proinflammatory cytokines.
AB  - BACKGROUND: Homocystinemia is a metabolic abnormality associated with endothelial
      dysfunction and increased cardiovascular disease risk. The underlying mechanisms
      of these effects, however, are obscure. OBJECTIVE: We examined the effect of
      asymmetrical dimethylarginine (ADMA) on endothelial dysfunction in methionine
      induced and chronic homocystinemia and evaluated the regulatory role of oxidative
      stress and proinflammatory cytokines on the release of ADMA. DESIGN: In this
      double-blind, placebo-controlled parallel group study, 30 subjects of both sexes
      (15 with homocystinemia and 15 healthy controls) underwent methionine loading,
      with simultaneous administration of a combination of vitamin C (2 g) plus alpha
      tocopherol (800 IU) or placebo. Endothelial function in forearm resistance
      vessels and concentrations of ADMA, oxidized LDL, and proinflammatory cytokines
      were determined at baseline and 4 h after methionine loading. RESULTS: Both
      chronic and methionine-induced homocystinemia were associated with increased
      oxidized LDL (P < 0.01), higher expression of the proinflammatory cytokine
      interleukin 6 (P < 0.05), and endothelial dysfunction (P < 0.01). Although ADMA
      rapidly increased in acute homocystinemia (P < 0.01) and was correlated with
      forearm hyperemic response at 4 h after methionine loading (r = -0.722, P =
      0.0001), it was not higher in subjects with high versus low fasting homocysteine.
      High-dose antioxidant treatment prevented methionine-induced elevation of
      oxidized LDL and interleukin 6 but failed to prevent the increase in ADMA or
      endothelial dysfunction. CONCLUSIONS: Both chronic and methionine-induced
      homocystinemia are characterized by increased oxidative stress and
      proinflammatory cytokines, which may contribute to the development of endothelial
      dysfunction. However, the ADMA pathway is activated only in acute homocystinemia
      by mechanisms not mediated by oxidized LDL or proinflammatory stimuli.

PMID- 17023706
TI  - Total energy expenditure in the Yakut (Sakha) of Siberia as measured by the
      doubly labeled water method.
AB  - BACKGROUND: Populations in transition to a Western lifestyle display increased
      incidences of obesity, type 2 diabetes, and other chronic diseases; the
      mechanisms responsible for these changes, however, remain incompletely
      understood. Although reduced physical activity has been implicated, few studies
      have accurately quantified energy expenditure in subsistence populations.
      OBJECTIVE: The aim of the study was to examine the relation of total energy
      expenditure (TEE) and activity [physical activity level (PAL), activity energy
      expenditure (AEE), and weight-adjusted AEE (AEE/kg)] with body composition and
      lifestyle in the Yakut (Sakha), an indigenous high-latitude Siberian group.
      DESIGN: We measured TEE using doubly labeled water and resting metabolic rate
      using indirect calorimetry in 28 young adults (14 women and 14 men) from
      Berdygestiakh, Russia. RESULTS: The men had higher TEE (12,983 compared with 9620
      kJ/d; P < 0.01), AEE (5248 compared with 3203 kJ/d; P < 0.05), AEE/kg (72.7
      compared with 48.8 kJ . kg(-1) . d(-1); P < 0.05), and PAL (1.7 compared with
      1.5; P = 0.09) than did the women, although this may reflect, in part, body size
      and composition differences. Overweight men and women had modestly higher TEEs
      than did lean participants; when adjusted for body size, activity levels were not
      significantly different between the groups. Persons with more traditional
      lifestyles had higher TEEs and PALs than did persons with more modernized
      lifestyles; this difference correlated with differences in participation in
      subsistence activities. CONCLUSIONS: Activity levels in the Yakut were lower than
      those in other subsistence groups, especially the women, and were not
      significantly different from those in persons in industrialized nations. Persons
      who participated in more subsistence activities and consumed fewer market foods
      had significantly higher activity levels.

PMID- 17023707
TI  - Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes.
AB  - BACKGROUND: Pregnancy is a condition in which the glycemic index (GI) may be of
      particular relevance because maternal glucose is the main energy substrate for
      intrauterine growth. OBJECTIVE: The aim was to compare the effects of low-GI and
      conventional dietary strategies on pregnancy outcomes in healthy women.
      Compliance and acceptability were also investigated. DESIGN: The subjects were
      assigned alternately to receive dietary counseling that encouraged either low-GI
      (LGI) carbohydrate foods or high-fiber, moderate-to-high GI (HGI) foods and were
      studied 5 times between <16 wk gestation and delivery. Of the 70 women who met
      the inclusion criteria, 62 completed the study (32 in the LGI and 30 in the HGI
      groups). Primary outcomes were measures of fetal size. RESULTS: The mean diet GI
      fell significantly in the LGI group but not in the HGI group. Compared with the
      LGI group, women in the HGI group gave birth to infants who were heavier (3408 +/
      78 compared with 3644 +/- 90 g; P = 0.051) and had a higher birth centile (48 +/
      5 compared with 69 +/- 5; P = 0.005), a higher ponderal index (2.62 +/- 0.04
      compared with 2.74 +/- 0.04; P = 0.03), and a higher prevalence of large-for
      gestational age (3.1% compared with 33.3%; P = 0.01). Women in the LGI group
      found the diet easier to follow. CONCLUSION: Because birth weight and ponderal
      index may predict chronic disease in later life, a low-GI diet may favorably
      influence long-term outcomes.

PMID- 17023708
TI  - Effects of moderate variations in macronutrient composition on weight loss and
      reduction in cardiovascular disease risk in obese, insulin-resistant adults.
AB  - BACKGROUND: Obese, insulin-resistant persons are at risk of cardiovascular
      disease. How best to achieve both weight loss and clinical benefit in these
      persons is controversial, and recent reports questioned the superiority of low
      fat diets. OBJECTIVE: We aimed to ascertain the effects of moderate variations in
      the carbohydrate and fat content of calorie-restricted diets on weight loss and
      cardiovascular disease risk in obese, insulin-resistant persons. DESIGN: Fifty
      seven randomly assigned, insulin-resistant, obese persons completed a 16-wk
      calorie-restricted diet with 15% of energy as protein and either 60% and 25% or
      40% and 45% of energy as carbohydrate and fat, respectively. Baseline and
      postweight-loss insulin resistance; daylong glucose, insulin, and triacylglycerol
      concentrations; fasting lipid and lipoprotein concentrations; and markers of
      endothelial function were quantified. RESULTS: Weight loss with 60% or 40% of
      energy as carbohydrate (5.7 +/- 0.7 or 6.9 +/- 0.7 kg, respectively) did not
      differ significantly, and improvement in insulin sensitivity correlated with the
      amount of weight lost (r = 0.50, P < 0.001). Subjects following the diet with 40%
      of energy as carbohydrate had greater reductions in daylong insulin and
      triacylglycerol (P < 0.05) and fasting triacylglycerol (0.53 mmol/L; P = 0.04)
      concentrations, greater increases in HDL-cholesterol concentrations (0.12 mmol/L;
      P < 0.01) and LDL particle size (1.82 s; P < 0.05), and a greater decrease in
      plasma E-selectin (5.6 ng/L; P = 0.02) than did subjects following the diet with
      60% of energy as carbohydrate. CONCLUSIONS: In obese, insulin-resistant persons,
      a calorie-restricted diet, moderately lower in carbohydrate and higher in
      unsaturated fat, is as efficacious as the traditional low-fat diet in producing
      weight loss and may be more beneficial in reducing markers for cardiovascular
      disease risk.

PMID- 17023709
TI  - Extruded rice fortified with micronized ground ferric pyrophosphate reduces iron
      deficiency in Indian schoolchildren: a double-blind randomized controlled trial.
AB  - BACKGROUND: Iron fortification of rice could be an effective strategy for
      reducing iron deficiency anemia in South Asia. OBJECTIVE: We aimed to determine
      whether extruded rice grains fortified with micronized ground ferric
      pyrophosphate (MGFP) would increase body iron stores in children. DESIGN: In a
      double-blind, 7-mo, school-based feeding trial in Bangalore, India, iron
      depleted, 6-13-y-old children (n = 184) were randomly assigned to receive either
      a rice-based lunch meal fortified with 20 mg Fe as MGFP or an identical but
      unfortified control meal. The meals were consumed under direct supervision, and
      daily leftovers were weighed. All children were dewormed at baseline and at 3.5
      mo. Iron status and hemoglobin were measured at baseline, 3.5 mo, and 7 mo.
      RESULTS: At baseline, the prevalences of iron deficiency and iron deficiency
      anemia in the total sample were 78% and 29%, respectively. After 7 mo of feeding,
      there was a significant increase in body iron stores in both study groups (P <
      0.001), with a greater increase in the iron group than in the control group (P <
      0.05). There was a significant time x treatment interaction for iron deficiency,
      which fell from 78% to 25% in the dewormed iron group and from 79% to 49% in the
      dewormed control group. Iron deficiency anemia decreased from 30% to 15% (NS) in
      the iron group but remained virtually unchanged in the control group (28% and
      27%). In sensory tests, the MGFP-fortified rice (fortified at 3 and 5 mg Fe/100
      g) was indistinguishable from natural rice, in both cooked and uncooked form.
      CONCLUSIONS: Extruded rice fortified with MGFP has excellent sensory
      characteristics. Fed in a school lunch meal, it increases iron stores and reduces
      the prevalence of iron deficiency in Indian children.

PMID- 17023710
TI  - Ascorbyl palmitate enhances iron bioavailability in iron-fortified bread.
AB  - BACKGROUND: One of the strategies to control iron deficiency anemia is the
      fortification of food with iron. A mechanism for improving the bioavailability of
      iron is to add an iron absorption promoter. OBJECTIVE: The objective was to
      determine the effect of ascorbyl palmitate (AP) on the bioavailability of iron in
      fortified bread made from refined wheat flour. DESIGN: The iron bioavailability
      of wheat flour fortified with either ferrous sulfate alone or ferrous sulfate
      plus AP was studied with the use of double radio iron (55Fe and 59Fe) erythrocyte
      incorporation in 14 women. RESULTS: Geometric mean (+/- range of 1 SD) iron
      absorption from the bread fortified with ferrous sulfate was 10.5% (4.1-27.0%).
      The addition of AP at molar ratios of AP to Fe of 2:1 and 4:1 significantly
      increased iron absorption [14.6% (5.9-36.1%) and 20.2% (10.6-38.6%),
      respectively; P < 0.001]. CONCLUSION: AP is a strong promoter of iron absorption
      from fortified bread because of its thermoresistant properties.

PMID- 17023711
TI  - Postprandial metabolic fate of tocotrienol-rich vitamin E differs significantly
      from that of alpha-tocopherol.
AB  - BACKGROUND: The detection of tocotrienols in human plasma has proven elusive, and
      it is hypothesized that they are rapidly assimilated and redistributed in various
      mammalian tissues. OBJECTIVE: The primary study objective was to evaluate the
      postprandial fate of tocotrienols and alpha-tocopherol in human plasma and
      lipoproteins. DESIGN: Seven healthy volunteers (4 males, 3 females) were
      administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction
      (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a
      tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8,
      and 24 h after supplementation. Concentrations of tocopherol and tocotrienol
      isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were
      measured at each interval. RESULTS: After intervention with TRF, plasma
      tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol
      peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly
      detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly
      lower than alpha-tocopherol concentrations. In comparison, plasma alpha
      tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol
      treatment and emerged as the major vitamin E isomer detected in plasma and
      lipoproteins during both the TRF and the alpha-tocopherol treatments.
      CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in
      significantly lower concentrations than is alpha-tocopherol. This finding
      confirms previous observations that, in the fasted state, tocotrienols are not
      detected in plasma. Tocotrienol transport in lipoproteins appears to follow
      complex biochemically mediated pathways within the lipoprotein cascade.

PMID- 17023712
TI  - Magnesium requirements: new estimations for men and women by cross-sectional
      statistical analyses of metabolic magnesium balance data.
AB  - BACKGROUND: Current recommendations for magnesium requirements are based on
      sparse balance data. OBJECTIVE: To provide new estimates of the average magnesium
      requirement for men and women, we pooled magnesium data from 27 different tightly
      controlled balance studies conducted at the US Department of Agriculture,
      Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand
      Forks, ND. DESIGN: Magnesium balance data (magnesium intake - [fecal magnesium +
      urinary magnesium]) (664 data points) were collected from 243 subjects (women: n
      = 150; weight: 71.6 +/- 16.5 kg; age: 51.3 +/- 17.4 y; men: n = 93, weight: 76.3
      +/- 12.5 kg; age: 28.1 +/- 8.1 y). Data from the last 6-14 d of each dietary
      period (> or =28 d) of each study were analyzed and were excluded if individual
      intakes of calcium, copper, iron, phosphorus, or zinc fell below respective
      estimated average requirements (EARs) or exceeded 99th percentiles of usual
      intakes of those elements (iron: above the upper limit) from the 1994 Continuing
      Survey of Food Intakes by Individuals. Daily intakes of magnesium ranged between
      84 and 598 mg. The relation between magnesium intake and magnesium output was
      investigated by fitting random coefficient models. RESULTS: The models predicted
      neutral magnesium balance [defined as magnesium output (Y) equal to magnesium
      intake (M)] at magnesium intakes of 165 mg/d [95% prediction interval (PI): 113,
      237 mg/d; Y = 19.8 + 0.880 M], 2.36 mg . kg(-1) . d(-1) (95% PI: 1.58, 3.38 mg .
      kg(-1) . d(-1); Y = 0.306 + 0.870 M), or 0.075 mg . kcal(-1) . d(-1) (95% PI:
      0.05, 0.11 mg . kcal(-1) . d(-1); Y = 0.011 + 0.857 M). Neither age nor sex
      affected the relation between magnesium intake and output. CONCLUSION: The
      findings suggest a lower magnesium requirement for healthy men and women than
      estimated previously.

PMID- 17023713
TI  - Docosahexaenoic acid supply in pregnancy affects placental expression of fatty
      acid transport proteins.
AB  - BACKGROUND: Better understanding of the mechanisms involved in docosahexaenoic
      acid (DHA) transfer to the neonate may contribute to improve dietary support for
      infants born prematurely to mothers with placental lipid transport disorders.
      OBJECTIVE: We studied whether DHA supplements modify the messenger RNA (mRNA)
      expression of placental lipid transport proteins to allow a selective transfer of
      DHA to the fetus. DESIGN: Healthy pregnant women (n = 136) received, in a double
      blind randomized trial, 500 mg DHA + 150 mg eicosapentaenoic acid, 400 microg 5
      methyl-tetrahydrofolic acid, 500 mg DHA + 400 microg 5-methyl-tetrahydrofolic
      acid, or placebo during the second half of gestation. We analyzed the fatty acid
      composition of maternal and cord blood phospholipids and of placenta; we
      quantified placental mRNA expression of fatty acid-transport protein 1 (FATP-1),
      FATP-4, FATP-6, fatty acid translocase, fatty acid-binding protein (FABP) plasma
      membrane, heart-FABP, adipocyte-FABP, and brain-FABP. RESULTS: The mRNA
      expression of the lipid carriers assayed did not differ significantly between the
      4 groups. However, the mRNA expression of FATP-1 and FATP-4 in placenta was
      correlated with DHA in both maternal plasma and placental phospholipids, although
      only FATP-4 expression was significantly correlated with DHA in cord blood
      phospholipids. Additionally, the mRNA expression of several membrane lipid
      carriers was correlated with EPA and DHA in placental triacylglycerols and with
      EPA in placental free fatty acids. CONCLUSIONS: Correlation of the mRNA
      expression of the membrane placental proteins FATP-1 and especially of FATP-4
      with maternal and cord DHA leads us to conclude that these lipid carriers are
      involved in placental transfer of long-chain polyunsaturated fatty acids.

PMID- 17023714
TI  - Energy expenditure and substrate oxidation predict changes in body fat in
      children.
AB  - BACKGROUND: The hypothesis that alterations in energy metabolism predict body fat
      gain is controversial. OBJECTIVE: The aim of this study was to determine which
      components of energy metabolism were most important in predicting fat gain in
      children aged 10.8 +/- 0.6 y. DESIGN: A 2-y longitudinal study to examine whether
      components of energy metabolism are predictors of body fat gain was conducted in
      114 preadolescent African American and white children aged 9-11 y by measuring
      total daily energy expenditure on the basis of doubly labeled water (DLW),
      resting metabolic rate, the thermic effect of food, energy expended in physical
      activity, and substrate oxidation after a meal. The primary endpoint was the 2-y
      change in percentage body fat (%BF). RESULTS: Individual variables of energy
      metabolism predicted up to 7% of the variance in changes in %BF over the 2-y
      interval in the whole group. Predictors of change in body fatness tended to be
      sex and race specific. Protein oxidation during a test meal explained a
      significant portion of the variance in change in %BF in the overall group and in
      nearly all of the subgroups. Multivariate prediction models accounted for 10-41%
      of the variance in change in %BF. Tanner stage at 2-y follow-up was highly
      predictive of change in body fatness and improved the overall prediction,
      accounting for 24-62% of the variance in change in %BF in those groups in which
      Tanner entered the model. CONCLUSION: This study provides evidence that total
      daily energy expenditure, resting metabolic rate, substrate oxidation, and total
      energy intake are predictors of gain in body fatness during late childhood in
      boys and girls.

PMID- 17023715
TI  - Glycemic index and glycemic load in relation to changes in body weight, body fat
      distribution, and body composition in adult Danes.
AB  - BACKGROUND: A diet with a high glycemic index (GI) and glycemic load (GL) may
      promote overconsumption of energy and increase the risk of weight gain.
      OBJECTIVE: The objective of the study was to investigate the relation between GI
      and GL of habitual diets and subsequent 6-y changes in body weight, body fat
      distribution, and body composition in a random group of adult Danes. DESIGN: A
      prospective cohort study was conducted in a subsample of men and women from the
      Danish arm of the Monitoring Trends and Determinants in Cardiovascular Disease
      study. The subsample comprised 185 men and 191 women born in 1922, 1932, 1942, or
      1952. A baseline health examination and a dietary history interview were carried
      out in 1987 and 1988; a follow-up health examination was performed in 1993 and
      1994. RESULTS: Positive associations between GI and changes in body weight
      (DeltaBW), percentage body fat (Delta%BF), and waist circumference (DeltaWC) were
      observed in women after adjustment for covariates. Significant GI x sex x
      physical activity interactions for DeltaBW, Delta%BF, and DeltaWC were observed,
      and the associations in the sedentary women were particularly positive. No
      significant associations with GI were observed in men, and no significant
      associations with GL were observed in either sex. CONCLUSIONS: High-GI diets may
      lead to increases in BW, body fat mass, and WC in women, especially in sedentary
      women, which suggests that physical activity may protect against diet-induced
      weight gain. No associations with GI were observed in men, which suggests sex
      differences in the association between GI and obesity development.

PMID- 17023716
TI  - Vitamin-mineral supplementation and the progression of atherosclerosis: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Laboratory and observational studies suggest that antioxidant and B
      vitamin supplementation may prevent atherosclerosis. Although trials have not
      shown a benefit of these supplements on clinical cardiovascular events, it is
      unknown whether they affect the progression of atherosclerosis as measured by
      imaging techniques. OBJECTIVE: The objective was to perform a meta-analysis of
      randomized controlled trials of the effect of vitamin-mineral supplementation on
      atherosclerosis progression. DESIGN: We searched the MEDLINE, EMBASE, and CENTRAL
      databases for relevant studies. No language restrictions were applied. We
      separately analyzed trials using antioxidants (vitamins E and C, beta-carotene,
      or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12).
      The progression of atherosclerosis was evaluated by B-mode ultrasound,
      intravascular ultrasound, or angiography. Effect sizes were calculated for the
      difference in slope of atherosclerosis progression between participants assigned
      to supplements and those assigned to the control group. RESULTS: In trials not
      involving percutaneous transluminal coronary angioplasty, the pooled effect size
      was -0.06 (95% CI: -0.20, 0.09; 7 trials) for antioxidants and -0.93 (95% CI: 
      2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous
      transluminal coronary angioplasty, the pooled relative risk of restenosis was
      0.82 (95% CI: 0.54, 1.26; 3 trials) for antioxidants and 0.84 (95% CI: 0.34,
      2.07; 2 trials) for B vitamins. CONCLUSION: Our meta-analysis showed no evidence
      of a protective effect of antioxidant or B vitamin supplements on the progression
      of atherosclerosis, thus providing a mechanistic explanation for their lack of
      effect on clinical cardiovascular events.

PMID- 17023717
TI  - Coffee consumption and markers of inflammation and endothelial dysfunction in
      healthy and diabetic women.
AB  - BACKGROUND: In several short-term studies, coffee consumption has been associated
      with impairment of endothelial function. OBJECTIVE: The objective was to assess
      the relation between long-term caffeinated and decaffeinated filtered coffee
      consumption and markers of inflammation and endothelial dysfunction. DESIGN: We
      conducted a cross-sectional study of 730 healthy women and 663 women with type 2
      diabetes from the Nurses' Health Study I cohort, who were aged 43-70 y and free
      of cardiovascular disease and cancer at the time blood was drawn (1989-1990).
      Dietary intake was assessed with a validated food-frequency questionnaire in 1986
      and 1990. RESULTS: About 77% of the healthy women consumed > or =1 cup (237 mL)
      caffeinated coffee/mo and 75% consumed > or =1 cup decaffeinated coffee/mo; the
      corresponding intakes for women with type 2 diabetes were 74% and 63%,
      respectively. In healthy women, no appreciable differences in plasma
      concentrations of the markers were found across categories of caffeinated coffee
      intake. In women with type 2 diabetes, higher caffeinated coffee consumption was
      associated with lower plasma concentrations of E-selectin (adjusted percentage
      change per 1 cup/d increment = -3.2%; P = 0.05) and C-reactive protein (adjusted
      percentage change = -10.2%; P < 0.001). Higher decaffeinated coffee consumption
      was associated with lower plasma concentrations of E-selectin (adjusted
      percentage change = -2.5%; P = 0.08) and C-reactive protein (adjusted percentage
      change = -7.9%; P = 0.02) only in healthy women. The results were similar when we
      also adjusted the models for other dietary factors and blood lipids and when we
      excluded participants with hypertension or hypercholesterolemia. CONCLUSIONS:
      These results indicate that neither caffeinated nor decaffeinated filtered coffee
      has a detrimental effect on endothelial function. In contrast, the results
      suggest that coffee consumption is inversely associated with markers of
      inflammation and endothelial dysfunction.

PMID- 17023718
TI  - Dietary fat intake and risk of coronary heart disease: the Strong Heart Study.
AB  - BACKGROUND: The results of previous studies on the association between dietary
      fat intake and coronary heart disease (CHD) incidence are inconsistent.
      OBJECTIVE: The aim of this study was to examine the association between dietary
      fat intake and CHD incidence in American Indians in the Strong Heart Study.
      DESIGN: A total of 2938 participants aged 47-79 y and free of CHD at the second
      examination (1993-1995) were examined and followed for CHD, nonfatal CHD, and
      fatal CHD events to 31 December 2002. Dietary intake was assessed by using a 24-h
      diet recall and was calculated as percentages of energy. RESULTS: Participants
      were followed for a mean (+/-SD) of 7.2 +/- 2.3 y. During follow-up, 436 incident
      CHD cases (298 nonfatal CHD and 138 fatal CHD events) were ascertained.
      Participants aged 47-59 y in the highest quartile of intake of total fat,
      saturated fatty acids, or monounsaturated fatty acids had higher CHD mortality
      than did those in the lowest quartile [hazard ratio (95% CI): 3.57 (1.21, 10.49),
      5.17 (1.64, 16.36), and 3.43 (1.17, 10.04), respectively] after confounders were
      controlled for. These associations were not observed for those aged 60-79 y.
      CONCLUSIONS: Total fat, saturated fatty acid, and monounsaturated fatty acid
      intake were strong predictors of CHD mortality in American Indians aged 47-59 y,
      independent of other established CHD risk factors. It may be prudent for American
      Indians to reduce their fat intake early in life to reduce the risk of dying from
      CHD.

PMID- 17023719
TI  - Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2
      y of age.
AB  - BACKGROUND: Low intakes of dietary antioxidants may contribute to increases in
      asthma and allergy. OBJECTIVE: We investigated the association of maternal total
      intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with
      wheezing and eczema in 2-y-old children. DESIGN: Subjects were 1290 mother-child
      pairs in an ongoing cohort study. Maternal dietary and supplement intakes were
      assessed by using a validated food-frequency questionnaire administered in the
      first and second trimesters. Antioxidant nutrient intakes were calculated, and
      the mean for each nutrient was considered to be the exposure during pregnancy.
      The outcomes of interest were any wheezing by the child during either the first
      or second year of life, recurrent wheezing in both years, and eczema in either
      the first or second year. RESULTS: No association was observed between maternal
      total intake of any antioxidant nutrient and eczema. In multivariate logistic
      regression models, the highest quartile compared with the lowest quartile of
      maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03]
      and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any
      wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for
      vitamin E and zinc, respectively). Similar results were obtained for recurrent
      wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc
      (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of
      intake for vitamin E and zinc, respectively). CONCLUSION: Our results suggest
      that higher maternal total intakes of antioxidants during pregnancy may decrease
      the risks for wheezing illnesses in early childhood.

PMID- 17023720
TI  - A randomized factorial study of the effects of long-term garlic and micronutrient
      supplementation and of 2-wk antibiotic treatment for Helicobacter pylori
      infection on serum cholesterol and lipoproteins.
AB  - BACKGROUND: Little is known about the long-term effects of garlic or
      micronutrient supplementation on total, HDL, and LDL cholesterol in disease-free
      persons. OBJECTIVE: We aimed to assess the effects of long-term supplementation
      with garlic and micronutrients and of short-term amoxicillin and omeprazole
      treatment on serum total, HDL, and LDL cholesterol in a rural Chinese population.
      DESIGN: We conducted a randomized, double-blind, placebo-controlled, 2 x 2 x 2
      and 2 x 2 factorial study of precancerous gastric lesions in 3411 subjects in
      Linqu County, Shandong Province, China. Thirty-four subjects were randomly
      selected from each of 12 treatment strata. Sera were analyzed at 3.3 and 7.3 y to
      measure effects on total, HDL, and LDL cholesterol after 2-wk twice-daily
      treatment with 1 g amoxicillin and 20 mg omeprazole and supplementation
      throughout the study with 1) 2 capsules twice daily, each containing 200 mg aged
      garlic extract and 1 mg steam-distilled garlic oil, or 2) twice-daily
      micronutrient capsules containing 250 mg vitamin C, 100 IU vitamin E, and 37.5 mg
      selenium. RESULTS: Regressions adjusted for covariates indicated increases of
      0.22 mmol total cholesterol/L (P = 0.01) and 0.19 mmol LDL/L (P = 0.02) after 7.3
      y of micronutrient supplementation, but no effect of garlic supplementation or
      short-term amoxicillin and omeprazole treatment. CONCLUSIONS: In this rural
      Chinese population with low meat intake and moderate cholesterol concentrations,
      long-term garlic supplementation had no effect on lipid profiles, whereas
      micronutrient supplementation was associated with small but significant increases
      in total and LDL-cholesterol concentrations at 7.3 y.

PMID- 17023721
TI  - Intervention with a low-fat, high-carbohydrate diet does not influence the timing
      of menopause.
AB  - BACKGROUND: Later age at menopause is associated with a greater risk of breast
      cancer. Dietary factors may at least partially influence breast cancer risk
      through an effect on the age at menopause. OBJECTIVE: We studied the effect of a
      low-fat, high-carbohydrate (LFHC) dietary intervention on the timing of menopause
      in women with greater risk of breast cancer. DESIGN: The study population
      included participants from an LFHC dietary intervention trial for the prevention
      of breast cancer in women with extensive mammographic density, a strong risk
      factor for breast cancer. Women who were premenopausal at baseline (n = 2611)
      were followed for an average of 7 y for menopause. Survival analysis was used to
      compare the time to menopause between the LFHC and control groups and to assess
      other factors associated with age at menopause. RESULTS: The LFHC intervention
      did not affect the time to natural menopause overall (P = 0.72 for log-rank test
      comparing study groups; n = 699 events). An observed interaction between study
      group and baseline body mass index (BMI; P = 0.01) indicated that the
      intervention group experienced earlier menopause than did the control group when
      BMI was low and that a higher BMI was associated with later menopause in the
      intervention group only. Greater parity, weight, and education were associated
      with later menopause, and greater age at first birth and baseline smoking were
      associated with earlier menopause. CONCLUSIONS: Overall, the LFHC dietary
      intervention did not influence the timing of menopause. Factors associated with
      age at menopause in this population were consistent with those reported in other
      populations.

PMID- 17023722
TI  - Dietary factors of one-carbon metabolism and prostate cancer risk.
AB  - BACKGROUND: Folate is hypothesized to be inversely associated with the risk of
      several cancers, but such a potential association has not been well studied for
      prostate cancer. Vitamin B-6, vitamin B-12, methionine, and alcohol can influence
      folate-related metabolism. OBJECTIVE: The objective was to investigate the
      associations between dietary factors of one-carbon metabolism and prostate cancer
      risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. DESIGN:
      Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary
      data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002.
      Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated
      from a 276-item modified dietary history questionnaire. Cox proportional hazard
      models, adjusted for age and vitamin supplement use, estimated relative risks
      (RR) and 95% CIs. RESULTS: Vitamin B-6 intake was inversely associated with
      prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% CI: 0.72,
      1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with
      significantly increased risk (RR = 1.36; 95% CI: 1.14, 1.96; P for trend = 0.01).
      No association between folate or alcohol intake and prostate cancer risk was
      observed. No differences were found in the above associations according to stage
      of disease or subgroups of several potential effect modifiers. CONCLUSIONS: We
      found no convincing evidence for a protective role of one-carbon metabolism
      against prostate cancer, although these observations can be generalized only to
      smokers. The possible modest protective association with vitamin B-6 and the
      significantly elevated risk with vitamin B-12 intake warrant further
      investigation.

PMID- 17023723
TI  - Colas, but not other carbonated beverages, are associated with low bone mineral
      density in older women: The Framingham Osteoporosis Study.
AB  - BACKGROUND: Soft drink consumption may have adverse effects on bone mineral
      density (BMD), but studies have shown mixed results. In addition to displacing
      healthier beverages, colas contain caffeine and phosphoric acid (H3PO4), which
      may adversely affect bone. OBJECTIVE: We hypothesized that consumption of cola is
      associated with lower BMD. DESIGN: BMD was measured at the spine and 3 hip sites
      in 1413 women and 1125 men in the Framingham Osteoporosis Study by using dual
      energy X-ray absorptiometry. Dietary intake was assessed by food-frequency
      questionnaire. We regressed each BMD measure on the frequency of soft drink
      consumption for men and women after adjustment for body mass index, height, age,
      energy intake, physical activity score, smoking, alcohol use, total calcium
      intake, total vitamin D intake, caffeine from noncola sources, season of
      measurement, and, for women, menopausal status and estrogen use. RESULTS: Cola
      intake was associated with significantly lower (P < 0.001-0.05) BMD at each hip
      site, but not the spine, in women but not in men. The mean BMD of those with
      daily cola intake was 3.7% lower at the femoral neck and 5.4% lower at Ward's
      area than of those who consumed <1 serving cola/mo. Similar results were seen for
      diet cola and, although weaker, for decaffeinated cola. No significant relations
      between noncola carbonated beverage consumption and BMD were observed. Total
      phosphorus intake was not significantly higher in daily cola consumers than in
      nonconsumers; however, the calcium-to-phosphorus ratios were lower. CONCLUSIONS:
      Intake of cola, but not of other carbonated soft drinks, is associated with low
      BMD in women. Additional research is needed to confirm these findings.

PMID- 17023725
TI  - Energy intake or energy expenditure?

PMID- 17023724
TI  - Maternal calcium supplementation and bone accretion in infants.

PMID- 17023726
TI  - Does cigarette smoking induce micronuclei in buccal cells?

PMID- 17023727
TI  - Sex-specific manifestations of Lofgren's syndrome.
AB  - MOTIVATION: It has been debated whether patients need to have erythema nodosum to
      be classified as having Lofgren's syndrome. In this study, we have therefore in
      detail evaluated and compared a large number of patients with an acute onset of
      sarcoidosis and bilateral hilar lymphadenopathy (BHL), with or without erythema
      nodosum (EN). This study is important because it may lead to a more accurate
      definition of Lofgren's syndrome, and an exact phenotype of patients is crucial
      in modern medical research. BACKGROUND: Lofgren's syndrome is commonly regarded
      as a distinct clinical entity. METHODS: We have in detail evaluated a large group
      of patients (n = 150) with an acute onset of sarcoidosis with BHL, in most cases
      with fever, EN, and/or bilateral ankle arthritis or periarticular inflammation.
      Within this group, 87 patients had EN (EN positive), whereas 63 were without EN
      (EN negative), though with distinct symmetric ankle inflammation. RESULTS: EN
      positive and EN-negative patients were identical in every aspect except that
      there were significantly more women in the EN-positive group: 58 women (67%) in
      the EN-positive group compared with only 17 (27%) women in the EN-negative group
      (p < 0.0001). In all other aspects, such as age, smoking habits, seasonal
      clustering of disease onset, rate of positive biopsies, chest radiography,
      pulmonary function, bronchoalveolar lavage cell distributions including the
      typically increased CD4/CD8 ratio, and clinical development of the disease, the
      EN-positive and EN-negative groups were close to identical. The two groups were
      also identically strongly associated with HLA-DRB1*0301/DQB1*0201, with 60
      (69.0%) and 44 (69.8%) patients having this particular HLA type in the EN
      positive and EN-negative groups, respectively. Such patients recovered to the
      same degree-that is, at almost 100%. CONCLUSIONS: We conclude that manifestations
      of Lofgren's syndrome differ between men and women, with EN found predominantly
      in women, whereas a marked periarticular inflammation of the ankles or ankle
      arthritis without EN is seen preferentially in men.

PMID- 17023728
TI  - Childhood chest illness and the rate of decline of adult lung function between
      ages 35 and 45 years.
AB  - RATIONALE: There is an association between childhood chest illness and impairment
      of adult ventilatory function. It has not yet been established whether
      respiratory illness in childhood predisposes to chronic obstructive pulmonary
      disease by accelerating the decline in adult lung function. OBJECTIVES: To
      determine the effects of childhood chest illness and smoking on the rate of
      decline of adult ventilatory function from the age of 35 to 45 yr in a large,
      nationally representative sample of British adults. METHODS: Spirometry
      measurements were compared at 35 and 45 yr of age in 1,158 adults participating
      in the British 1958 Birth Cohort. Multiple regression analysis was used to
      measure the association between childhood chest illness and within-person change
      in spirometric volumes between age 35 and 45 yr, adjusting for potential
      confounding factors. MEASUREMENTS AND MAIN RESULTS: The mean reduction in FEV(1)
      between ages 35 and 45 yr was 35 ml/yr. Compared with subjects without the
      relevant respiratory history, the rate of decline was not significantly
      associated with pneumonia (mean difference, -0.2; 95% confidence interval, -6.1
      to +5.8 ml/yr), whooping cough (0.7, -5.1 to +6.5 ml/yr), wheeze by age 7 yr
      (0.4, -5 to +5.9 ml/yr), or wheeze onset by age 8 to 16 yr (-3.4, -10.5 to +3.6
      ml/yr). A similar pattern emerged for forced vital capacity. CONCLUSIONS:
      Childhood chest illness does not adversely affect the rate of decline of lung
      function in mid-adult life.

PMID- 17023729
TI  - The predisposition to inspiratory upper airway collapse during partial
      neuromuscular blockade.
AB  - RATIONALE: Partial neuromuscular transmission failure by acetylcholine receptor
      blockade (neuromuscular blockade) or antibody-mediated functional loss
      (myasthenia gravis), even with a magnitude of muscle weakness that does not evoke
      respiratory symptoms, can evoke dysphagia and decreased inspiratory airflow, and
      increases the risk of susceptible patients to develop severe pulmonary
      complications. OBJECTIVES: To assess whether impaired neuromuscular transmission
      predisposes individuals to inspiratory upper airway collapse, we assessed
      supraglottic airway diameter and volume by respiratory-gated magnetic resonance
      imaging, upper airway dilator muscle function (genioglossus force and EMG), and
      changes in lung volume, respiratory timing, and peripheral muscle function
      before, during, and after partial neuromuscular blockade in healthy, awake
      volunteers. MEASUREMENTS AND MAIN RESULTS: Partial neuromuscular blockade (train
      of-four [TOF] ratio: 0.5 and 0.8) was associated with the following: (1) a
      decrease of inspiratory retropalatal and retroglossal upper airway volume to 66
      +/- 22 and 82 +/- 12% of baseline, which was significantly more intense in the
      retropalatal area; (2) an attenuation of the normal increase in anteroposterior
      upper airway diameter during forced inspiration to 74 +/- 18% of baseline; (3) a
      decrease in genioglossus activity during maximum voluntary tongue protrusion to
      39 +/- 19% (TOF, 0.5) and 73 +/- 29% (TOF, 0.8) of baseline; and (4) no effects
      on upper airway size during expiration, lung volume, and respiratory timing.
      CONCLUSIONS: Thus, impaired neuromuscular transmission, even to a degree
      insufficient to evoke respiratory symptoms, markedly impairs upper airway
      dimensions and function. This may be explained by an impairment of the balance
      between upper airway dilating forces and negative intraluminal pressure generated
      during inspiration by respiratory "pump" muscles.

PMID- 17023731
TI  - All-trans-retinoic acid prevents radiation- or bleomycin-induced pulmonary
      fibrosis.
AB  - RATIONALE: Although radiotherapy is effective in treating lung cancers, resultant
      pulmonary injury is the main obstacle. Pulmonary fibrosis is characterized by
      progressive worsening in pulmonary function leading to high incidence of death.
      Currently, however, there has been little progress in effective preventive and
      therapeutic strategies. OBJECTIVES: Previously, we reported that all-trans
      retinoic acid (ATRA) reduced both irradiation-induced interleukin (IL)-6
      production in lung fibroblasts and IL-6-dependent cell growth, and also directly
      inhibited the proliferation of lung fibroblasts after irradiation. In this study,
      we examined the preventive effect of ATRA on the progression of lung fibrosis
      both in irradiated and bleomycin-treated mice. MEASUREMENTS: We performed
      histologic examinations and quantitative measurements of IL-6, transforming
      growth factor (TGF)-beta(1), and collagen type Ialpha1 (COL1A1) in irradiated and
      bleomycin- treated mouse lung tissues with or without the administration of ATRA.
      RESULTS: Lethal irradiation effect was reduced by intraperitoneal administration
      of ATRA, and the overall survival rate at 16 wk was 30.0% without ATRA (n = 11),
      whereas it was 81.8% (n = 10) in the treatment group (p = 0.04). In vitro studies
      disclosed that the administration of ATRA reduced (1) irradiation-induced
      production of IL-6, TGF-beta(1), and collagen from IMR90 cells, and (2) IL-6
      dependent proliferation and TGF-beta(1)-dependent transdifferentiation of the
      cells, which could be the mechanism underlying the preventive effect of ATRA on
      lung fibrosis. Furthermore, ATRA ameliorated bleomycin-induced fibrosis in mouse
      lung tissues. CONCLUSIONS: These data may provide a rationale to explore clinical
      use of ATRA for the prevention of radiation-induced lung fibrosis and other
      pathologic conditions involving pulmonary fibrosis.

PMID- 17023730
TI  - Glutathione s-transferases M1 and P1 prevent aggravation of allergic responses by
      secondhand smoke.
AB  - RATIONALE: Secondhand tobacco smoke (SHS) and traffic-related air pollutants are
      associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can
      interact with allergens in exacerbating allergic airway diseases through
      generation of reactive oxygen species. Glutathione S-transferases (GSTs)
      metabolize reactive oxygen species and detoxify electrophilic xenobiotics present
      in SHS and DEPs. OBJECTIVES: We tested the hypotheses that functional GSTM1-null
      genotype and GSTP1 codon 105 variants (Ile105 and Val105) are determinants of
      allergic responses to SHS, and that responses to SHS and DEPs are correlated.
      METHODS AND MEASUREMENTS: In a randomized, placebo-controlled crossover trial, 19
      ragweed allergen-sensitive subjects who had previously participated in a DEP
      trial were challenged intranasally with allergen after having been exposed to
      either clean air or SHS at separate visits. Nasal allergen-specific IgE,
      histamine, IL-4, and IFN-gamma levels were measured before and after allergen
      challenge. MAIN RESULTS: Individuals with GSTM1-null or GSTP1 Ile105 genotypes
      showed larger nasal responses to allergens with SHS compared with clean air.
      GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects
      (median, 173.3 vs. 46.7 U/ml; p = 0.03), and the Ile105 GSTP1 genotype subjects
      had increased histamine (median, 10.2 vs. 4.6 nM; p = 0.01) after SHS plus
      allergen challenge. Responses to SHS and DEPs were correlated. Enhancement of IgE
      and histamine was greatest in the subjects with both the GSTM1-null and GSTP1
      Ile/Ile genotypes. CONCLUSIONS: GSTM1 and GSTP1 are important cytoprotective
      factors that reduce SHS and DEP exacerbation of allergic responses.

PMID- 17023732
TI  - Association of protein C and type 1 plasminogen activator inhibitor with primary
      graft dysfunction.
AB  - BACKGROUND: Acute lung injury is characterized by hypercoagulability and impaired
      fibrinolysis. We hypothesized that lower protein C and higher type 1 plasminogen
      activator inhibitor (PAI-1) levels in plasma would be associated with primary
      graft dysfunction (PGD) after lung transplantation. DESIGN: Prospective,
      multicenter cohort study. METHODS: We measured plasma levels of protein C and PAI
      1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion
      in 128 lung transplant recipients at six centers. The primary outcome was grade 3
      PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after
      transplantation. Biomarker profiles were evaluated using logistic regression and
      generalized estimating equations. RESULTS: Patients who developed PGD had lower
      protein C levels 24 h posttransplantation than did patients without PGD (mean +/-
      SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002).
      Patients with PGD also had PAI-1 levels that were almost double those of patients
      without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001).
      Throughout the 72-h postoperative period, protein C levels were significantly
      lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD
      than in others. These differences persisted despite adjustment for potential
      confounders in multivariate analyses. Higher recipient pulmonary artery
      pressures, measured immediately pretransplantation, were associated with higher
      PAI-1 levels and increased risk of PGD. CONCLUSION: Lower postoperative protein C
      and higher PAI-1 plasma levels are associated with PGD after lung
      transplantation. Impaired fibrinolysis and enhanced coagulation may be important
      in PGD pathogenesis.

PMID- 17023733
TI  - In vivo imaging of the bronchial wall microstructure using fibered confocal
      fluorescence microscopy.
AB  - RATIONALE: Fibered confocal fluorescence microscopy (FCFM) is a new technique
      that produces microscopic imaging of a living tissue through a 1-mm fiberoptic
      probe that can be introduced into the working channel of the bronchoscope.
      OBJECTIVES: To analyze the microscopic autofluorescence structure of normal and
      pathologic bronchial mucosae using FCFM during bronchoscopy. METHODS: Bronchial
      FCFM and spectral analyses were performed at 488-nm excitation wavelength on two
      bronchial specimens ex vivo and in 29 individuals at high risk for lung cancer in
      vivo. Biopsies of in vivo FCFM-imaged areas were performed using autofluorescence
      bronchoscopy. RESULTS: Ex vivo and in vivo microscopic and spectral analyses
      showed that the FCFM signal mainly originates from the elastin component of the
      basement membrane zone. Five distinct reproducible microscopic patterns were
      recognized in the normal areas from the trachea down to the more distal
      respiratory bronchi. In areas of the proximal airways not previously biopsied,
      one of these patterns was found in 30 of 30 normal epithelia, whereas alterations
      of the autofluorescence microstructure were observed in 19 of 22 metaplastic or
      dysplastic samples, five of five carcinomas in situ, and two of two invasive
      lesions. Disorganization of the fibered network could be found on 9 of 27
      preinvasive lesions, compatible with early disruptions of the basement membrane
      zone. FCFM alterations were also observed in a tracheobronchomegaly syndrome and
      in a sarcoidosis case. CONCLUSIONS: Endoscopic FCFM represents a minimally
      invasive method to study specific basement membrane alterations associated with
      premalignant bronchial lesions in vivo. The technique may also be useful to study
      the bronchial wall remodeling in nonmalignant chronic bronchial diseases.

PMID- 17023734
TI  - Cigarette smoke impacts immune inflammatory responses to influenza in mice.
AB  - RATIONALE: Studies have shown that cigarette smoke impacts respiratory host
      defense mechanisms; however, it is poorly understood how these smoke-induced
      changes impact the overall ability of the host to deal with pathogenic agents.
      OBJECTIVE: The objective of this study was to investigate the impact of
      mainstream cigarette smoke exposure on immune inflammatory responses and viral
      burden after respiratory infection with influenza A. METHODS: C57BL/6 mice were
      sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 x 10(3) pfu
      (low dose) or 2.5 x 10(5) pfu (high dose) influenza virus. MEASUREMENTS AND MAIN
      RESULTS: Although smoke exposure attenuated the airway's inflammatory response to
      low-dose infection, we observed increased inflammation in smoke-exposed compared
      with sham-exposed mice after infection with high-dose influenza, despite a
      similar rate of viral clearance. The heightened inflammatory response was
      associated with increased expression of tumor necrosis factor-alpha, interleukin
      6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke
      exposure did not interfere with the development of influenza-specific memory
      responses; sham- and smoke-exposed animals were equally protected upon viral
      rechallenge. CONCLUSION: Our study suggests that, in mice, cigarette smoke
      affects primary antiviral immune-inflammatory responses, whereas secondary immune
      protection remains intact.

PMID- 17023735
TI  - Volume reduction surgery impairs immediate postoperative pulmonary function in
      canine emphysema.
AB  - RATIONALE: In severe pulmonary emphysema, lung volume reduction surgery (LVRS)
      improves pulmonary function over a 2-yr period in selected patients. However, the
      changes in lung function and maximal flow (Vmax) occurring immediately
      postoperatively are not clear and may contribute to the high morbidity observed.
      In the present study, we used a chronic canine model of upper lobe emphysema to
      address this question. METHODS: Bilateral upper lobe emphysema was produced by
      the intrabronchial administration of papain. Measurements were made before and
      immediately after LVRS was performed. A vacuum-assisted surgical system (VALR
      Surgical System; Spiration, Redmond, WA) that deploys a compression sleeve over
      portions of the disease tissue was used to produce LVRS. Changes in Vmax were
      interpreted in terms of the wave-speed theory of flow limitation in which a
      pressure sensor was placed into the airway to determine the site of limitation
      and intrabronchial pressures. RESULTS: In the emphysema group, total lung
      capacity postemphysema increased to approximately 20% above the preemphysema
      value, whereas Vmax was reduced as compared with a control group. After LVRS,
      tidal respiratory compliance and Vmax decreased, whereas lung elastic recoil and
      frictional resistance increased in both the emphysema and control groups as
      compared with presurgery. CONCLUSION: The acute effect of LVRS leads to an
      impairment in lung mechanical properties. These changes could contribute to
      ventilatory complications, including the difficulty of weaning patients from
      mechanical ventilation and the mortality observed from this procedure.

PMID- 17023737
TI  - Isolation and characterization of a novel uronic acid-containing acidic
      glycosphingolipid from the ascidian Halocynthia roretzi.
AB  - A novel uronic acid-containing glycosphingolipid (UGL-1) was isolated from the
      ascidian Halocynthia roretzi. UGL-1 was prepared from chloroform-methanol
      extracts and purified by the use of successive column chromatography on DEAE
      Sephadex, Florisil, and Iatrobeads. Chemical structural analysis was performed
      using methylation analysis, gas chromatography, gas chromatography-mass
      spectrometry, matrix-assisted laser-desorption/ionization time-of-flight mass
      spectrometry, and 1H-NMR spectra. The chemical structure of UGL-1 was determined
      to be a glucuronic acid-containing glycosphingolipid, Galbeta1-4(Fucalpha1
      3)GlcAbeta1-1Cer. The ceramide component was composed of C16:0 and C18:0 acids
      and C16-, C17-, and C18-phytosphingosines as major components.

PMID- 17023736
TI  - Endogenous secretory receptor for advanced glycation end products in non-small
      cell lung carcinoma.
AB  - RATIONALE: The receptor for advanced glycation end products is a multiligand
      receptor that plays an important role in regulating the invasiveness and
      metastatic potential of cancer cells. A recently discovered novel splice variant,
      the endogenous secretory receptor for advanced glycation end products, mediates
      the receptor for advanced glycation end-product-associated cell responses by
      functioning as a decoy receptor. OBJECTIVES: To evaluate the expression pattern
      of endogenous secretory receptor for advanced glycation end products in non-small
      cell lung carcinoma, and analyze its impact on prognosis. METHODS: We performed
      immunohistochemical evaluation in 182 non-small cell lung carcinoma surgical
      specimens. The effect of an overexpressed receptor in cancer cell proliferation
      was also evaluated. MEASUREMENTS AND MAIN RESULTS: The endogenous secretory
      receptor for advanced glycation end-product expression in cytoplasm was reduced
      or absent in 137 of the 182 (75%) carcinomas in contrast to normal lung tissues.
      mRNA expression was also suppressed in cancer cells. Overexpression of the
      secretory receptor in lung cancer cell lines had an inhibitory effect on cell
      proliferation, suggesting the reduced receptor expression accelerated tumor
      growth. Among patients with low expression of the cytoplasmic secretory receptor,
      the overall survival rate was significantly lower than that of patients with
      normal expression (p = 0.0003). This association was most prominent in TNM stage
      I patients (p = 0.0001). In a multivariate analysis, endogenous secretory
      receptor immunoreactivity was an independent prognostic factor with a relative
      risk of 3.1. CONCLUSIONS: The cytoplasmic endogenous secretory receptor for
      advanced glycation end-product expression has the potential to be a prognostic
      factor for predicting the outcome of curative surgery in patients with non-small
      cell lung carcinoma.

PMID- 17023738
TI  - Novel anti-cholesterol monoclonal immunoglobulin G antibodies as probes and
      potential modulators of membrane raft-dependent immune functions.
AB  - Natural autoantibodies against cholesterol are present in the sera of all healthy
      individuals; their function, production, and regulation, however, are still
      unclear. Here, we managed to produce two monoclonal anti-cholesterol antibodies
      (ACHAs) by immunizing mice with cholesterol-rich liposomes. The new ACHAs were
      specific to cholesterol and to some structurally closely related 3beta-hydroxyl
      sterols, and they reacted with human lipoproteins VLDL, LDL, and HDL. They bound,
      usually with low avidity, to live human or murine lymphocyte and monocyte
      macrophage cell lines, which was enhanced substantially by a moderate papain
      digestion of the cell surface, removing some protruding extracellular protein
      domains. Cell-bound ACHAs strongly colocalized with markers of cholesterol-rich
      lipid rafts and caveolae at the cell surface and intracellularly with markers of
      the endoplasmic reticulum and Golgi complex. These data suggest that these IgG
      ACHAs may serve as probes of clustered cholesterol (e.g., different lipid rafts)
      in live cells and thus may also have immunomodulatory potential.

PMID- 17023739
TI  - Methodologies for assessment of apical and coronal leakage of endodontic filling
      materials: a critical review.
AB  - Apical leakage continues to be a topic of great interest, because in spite of the
      advances in Endodontics, clinical failures still occur. Most failures are
      probably attributed to the proliferation of bacteria that remain viable after
      chemical-mechanical preparation and cause periapical tissue irritation. Coronal
      leakage has aroused researchers' interest over the last few years, since canals
      may be re-contaminated after loss of coronal sealing or fracture of the remaining
      tooth. In this review, the various methodologies used for assessing root canal
      sealing capacity are critically analyzed, as they are not standardized, which
      makes it difficult to compare the results obtained when different methodologies
      are used, even though the same substrate is being assessed.

PMID- 17023740
TI  - The role of Carisolv and different auxiliary chemical substances in the removal
      of bovine root canal smear layer.
AB  - To evaluate the effectiveness of Carisolv and different auxiliary chemical
      substances in root canal smear layer (SL) removal. SL was produced in the centre
      of 40 hemi-disks of bovine root dentine. The samples were divided into four
      irrigation groups (G): GI (control) - 0.9% NaCl; GII - 1% NaOCl + 0.9% NaCl; GIII
      - Carisolv + 0.9% NaCl; GIV - 1% NaOCl + 10% citric acid solution + 0.9% NaCl.
      The photomicrographs (SEM analysis) were coded (0 - absence of SL; 1 - moderate
      SL; 2 - dense SL with visible tubules; 3 - dense SL with no visible tubules). GIV
      was more effective in SL removal (P < 0.01). It should be noted that GI and GIII
      obtained score 3 in 100% of the samples (P > 0.01). CONCLUSION: NaOHCl, citric
      acid and NaCl solutions, when used together, presented a better performance in
      the removal of SL when compared to the other solutions.

PMID- 17023741
TI  - Aberrant expression of Smad4, a TGF-beta signaling molecule, in oral squamous
      cell carcinoma.
AB  - Although carcinogenesis of oral squamous cell carcinoma (OSCC) has been studied
      by many investigators in the past decade, the available evidence about its
      molecular mechanism is inconclusive. The objective of the present study was to
      compare expression of Smad4, a signaling molecule of the transforming growth
      factor beta (TGF-beta) pathway, between OSCC and normal oral mucosa. We assayed
      expression of Smad4 in OSCC and normal oral mucosa by performing
      immunohistochemistry using paraffin-embedded tissue samples. We also compared
      expression of Smad4 protein between OSCC lines and normal oral keratinocytes,
      using Western blot analysis. Smad4 expression was observed in only 60% of OSCC
      tissue samples, whereas it was observed in 82% of normal oral mucosa samples.
      Reduced Smad4 expression was clearly observed in all OSCC lines, compared with
      normal oral keratinocytes. These findings suggest that aberration of the TGF-beta
      pathway, as indicated by a reduction or absence of Smad4 expression, promotes
      carcinogenesis of OSCC.

PMID- 17023742
TI  - Study of the clinical usefulness of a dental drug system for selective reduction
      of mutans streptococci using a case series.
AB  - The aim of this study was to evaluate the clinical efficacy and safety of a
      dental drug delivery system (3DS) for the selective reduction of mutans
      streptococci. Twenty patients with high levels of mutans streptococci in saliva
      participated. The efficacy of 0.2% chlorhexidine (CHX) delivered by 3DS in
      reducing the salivary levels of mutans streptococci compared with total
      streptococci and lactobacilli was investigated. Each subject was treated by
      professional mechanical tooth cleaning (PMTC) and subsequently individual trays
      with CHX for 5 min. Salivary bacterial samples were taken at the baseline and
      weeks 1-12. A significant reduction in the colony count of mutans streptococci
      was observed during the first 4 weeks compared with the baseline count, while no
      significant decrease in the count of total streptococci or lactobacilli was found
      during 12 weeks. In particular, the proportion of mutans streptococci in total
      streptococci remained low after 12 weeks. Our results indicate that the new 3DS
      used in combination with PMTC appears to be a promising intraoral drug delivery
      system which, when used with a low CHX concentration selectively, effectively
      reduces mutans streptococci in the oral cavity with no adverse effects.

PMID- 17023743
TI  - Comparative studies on the effect of crude aqueous (CA) and solvent (CM) extracts
      of clove on the cariogenic properties of Streptococcus mutans.
AB  - A study was conducted to compare the efficiency of crude aqueous (CA) and solvent
      extracts (CM) of clove on the caries-inducing properties of Streptococcus mutans.
      The cariogenic properties investigated included the cell adhesion, cell-surface
      hydrophobicity and glucan synthesis activities of S. mutans. There was a
      significant difference between the effect of the CA and CM extracts on the
      adhesion of S. mutans (P < 0.05) within a concentration range of 5-15 mg/ml, the
      CM extract demonstrating a slightly higher inhibitory effect. However, the effect
      of the CM extract on the cell-surface hydrophobicity of S. mutans was weaker than
      that of the CA extract. The two extracts were found to reduce the synthesis of
      water-insoluble glucan (WIG) by almost 50% at a concentration as low as 0.5 mg/ml
      and the CM extract exhibited a significantly higher inhibitory effect than the CA
      extract (P < 0.05). The present findings indicate that both the CA and CM
      extracts exert inhibitory effects on the cariogenic properties of S. mutans and
      that the CA extract is as equally effective as the CM extract.

PMID- 17023744
TI  - Influence of surface roughness on crack formation in a glass-ceramic bonded to a
      resin composite base.
AB  - The objective of the present study was to assess the influence of the roughness
      of a loaded surface on crack formation in a mica-based glass-ceramic bonded to a
      resin composite base. Five different surface roughnesses were created on glass
      ceramic discs by serial wet-grinding with silicone carbide abrasives. The
      thicknesses of the ceramic discs were 1.50 +/- 0.01 mm. Resin composite discs
      were bonded to the ceramic surfaces opposite to the ground surfaces using an
      adhesive resin composite cement and a silane coupling agent. A compressive load
      was then applied at the center of the ground ceramic surface. The loads at
      initial radial and cone crack formations in the ceramic were measured
      macroscopically. In three of the five groups, the initial radial crack formations
      could not be observed due to the high roughness of these surfaces. Statistical
      analysis was performed using Student's t test for initial radial cracks and one
      way ANOVA for the cone cracks. There were no significant differences between the
      two groups for the initial radial cracks or among the five groups for the cone
      cracks (P < 0.05). The roughness of the loaded surface had no influence on crack
      formation in the bonded mica-based glass-ceramic.

PMID- 17023745
TI  - Influence of moisture conditions on dentin bond strength of single-step self-etch
      adhesive systems.
AB  - This study was conducted to clarify the influence of dentin surface moisture on
      bond strength of single-step self-etch adhesive systems. The adhesive systems
      used were Adper Prompt L-Pop (AP), Clearfil tri-S Bond (CT), Fluoro Bond Shake
      One (FB), G-Bond (GB), and One-Up Bond F Plus (OF). Bovine mandibular incisors
      were wet-ground with #600 SiC to expose the labial dentin. After rinsing with tap
      water, the dentin surface was dried with air for 10 sec (Dry condition) or
      blotted (Wet condition). Adhesives were applied according to each manufacturer's
      instructions, followed by resin composite polymerization. Ten samples per test
      group were stored in distilled water at 37 degrees C for 24 h, then shear tested
      at a crosshead speed of 1.0 mm/min. The data were analyzed by Student's t test
      and Tukey HSD test at a probability level of 0.05. The mean bond strengths for
      Dry condition ranged from 13.9 MPa to 18.2 MPa, and those for Wet condition
      ranged from 7.1 MPa to 18.4 MPa. Significantly lower bond strengths were obtained
      for the Wet condition for GB, FB, and OF. Failure after the test was commonly due
      to adhesive breakdown associated with partial cohesive failure in the dentin.
      These data suggest that air-drying of the dentin surface is appropriate for the
      adhesive systems tested.

PMID- 17023746
TI  - Comparison between semi-automated segmentation and manual point-counting methods
      for quantitative analysis of histological sections.
AB  - The aim of the present study was to compare results obtained using the manual
      point-counting method with results obtained using the semi-automated segmentation
      method, in the quantitative evaluation of histological sections by light
      microscopy. The tongues of 40 rats (Ratus norvergicus) were processed using the
      paraffin technique, in which a 5-mum-thick tissue slice cut from each tongue is
      stained with picrosirius and methyl green. Three digital images were captured
      randomly from each section, which were later converted to black-and-white. The
      collagen fibers shown in each image were quantified using the semi-automated
      segmentation method and the manual point-counting method. The results obtained
      using the 2 different quantification methods were compared using the paired t
      test and Pearson's correlation test, with statistical analysis using the methods
      of Bland and Altman. The t-test indicated that there was no significant
      difference in results between the 2 different quan-tification methods. Pearson's
      correlation test indicated a strong correlation (r = 0.987), and a comparison of
      the methods using the Bland and Altman plot indicated no significant error. These
      findings indicate that both quantification methods can be reliably used to
      evaluate tissue sections, without discrepancies between the 2 methods.

PMID- 17023747
TI  - Hypervariable region structure and polymorphism of mtDNA from dental pulp and a
      family analysis.
AB  - Nucleotide sequences of the hypervariable region in the D-loop of mitochondrial
      DNA (mtDNA) were analyzed using DNA extracted from 140 old dental pulp samples.
      These sequences were compared with the sequence reported by Anderson et al.
      Nucleotide substitution in the HV1 region was identified at 77 positions. A C-to
      T transition at position 16223 (C16223T) was most frequently detected (77.9%).
      Fourteen types of C-stretch sequence patterns were detected and the same sequence
      as Anderson had the highest frequency (57.9%). In the HV2 region, base
      transitions were identified at 56 positions. A263G was identified in all samples.
      Seven types of C-stretch were detected, but none had the same sequence as
      Anderson. In the HV3 region, base transitions were identified at 21 positions.
      T489C was most frequently identified (64.3%). Five types of C-stretch were
      detected, and the same sequence as Anderson accounted for 92.9%. The 140 samples
      were classified into 128 kinds by the sequence patterns of the HV region. Next,
      using the blood and oral mucosa epithelium from 23 subjects comprising four
      generations in a family line, the hereditary relationship of mtDNA was examined.
      All mtDNA types of the first-generation mother were infallibly inherited by the
      fourth generation.

PMID- 17023748
TI  - Association between recurrent aphthous stomatitis and salivary thiocyanate
      levels.
AB  - The aim of this work was to investigate the association between recurrent
      aphthous stomatitis (RAS) and salivary thiocyanate levels. The sample comprised
      men and women of age ranging from 15 to 55 years, who were allocated to four
      groups: 28 patients in RAS active phase (group 1); 28 patients in RAS remission
      phase (group 2); 29 smokers (group 3); 26 non-smokers without RAS (group 4).
      Samples of whole saliva mechanically stimulated were collected, and thiocyanate
      levels were measured. The results were analyzed by ANOVA and paired t-test. Mean
      salivary thiocyanate values were 0.55 mM, 0.64 mM, 2.36 mM and 0.96 mM in groups
      1 (active RAS), 2 (remission RAS), 3 (smokers) and 4 (control), respectively.
      There was no significant difference in thiocyanate levels when groups 1 and 2
      were compared with group 4. Group 3 showed a significantly higher thiocyanate
      concentration when compared with groups 1, 2 and 4 (P < 0.05). There was no
      significant difference in thiocyanate levels between groups 1 and 2 (P > 0.05).
      It is therefore suggested that there is no association between RAS and salivary
      thiocyanate levels.

PMID- 17023749
TI  - Oral plexiform neurofibroma not associated with neurofibromatosis type I: case
      report.
AB  - An unusual case of isolated plexiform neurofibroma arising in the oral cavity
      without other clinical manifestations or family history of neuro-fibromatosis-1
      (NF-1) is described. The tumor was histopathologically analyzed and an
      immunohistochemical panel comprising S-100 protein, epithelial membrane antigen
      (EMA), collagen IV, and CD34 was performed. Typical features of plexiform
      neurofibroma characterized by enlarged nerve fascicles composed of elongated
      nuclei and scant cytoplasm cells were identified. Subjacent to the oral
      epithelium, tactile-like bodies were also detected. On the basis of this report,
      we would like to emphasize that plexiform neurofibroma can occur in the oral
      cavity as a benign isolated tumor in patients without other stigmata of NF-1.

PMID- 17023750
TI  - Cleidocranial dysplasia: importance of radiographic images in diagnosis of the
      condition.
AB  - Cleidocranial dysplasia (CCD) is a rare syndrome usually caused by an autosomal
      dominant gene, although 40% of cases of CCD appear spontaneously with no apparent
      genetic cause. This condition is characterized by several cranial malformations
      and underdevelopment, absence of the clavicles, and multiple supernumerary and
      impacted permanent teeth. The diagnosis of this condition is usually based on the
      presence of the main features (supernumerary teeth, partial or total absence of
      one or both the clavicles, and bony malformations) and on clinical and familial
      evidence. The bony and dental features of CCD may be visualized on radiographic
      images of the face and skull. Here, we present a familial case of CCD and discuss
      the importance of dental radiographs in diagnosis of the condition.

PMID- 17023751
TI  - [Chronic pancreatitis--complications and long-term outcome].

PMID- 17023752
TI  - [Diagnostic criteria and treatment strategy of acute cholangitis and
      cholecystitis--clinical practice guidelines].

PMID- 17023753
TI  - [Sclerosing cholangitis: clinical features and recent understandings of
      pathophysiology].

PMID- 17023754
TI  - [A case of localized AL-type amyloidosis of the stomach].
AB  - A 78-year-old woman was admitted to our hospital for treatment of liver cirrhosis
      and an esophageal varix. Endoscopy revealed a protruding nodular lesion with a
      transparent smooth surface proximal to the pylorus, which was accompanied by a
      partly yellow-whitish spot. A depressed lesion with an even edge was found.
      Histologically, the protruding lesion and depressed lesion showed amyloid
      deposits, mainly in the mucosal layer. The lesions were found to correspond to AL
      type amyloidosis by immunochemical analysis. General examination showed no other
      amyloid deposits. Thus, we diagnosed localized amyloidosis of the stomach.

PMID- 17023755
TI  - [A case of ulcerative colitis with hematuria and renal dysfunction after
      leukocytapheresis].
AB  - A 53-year-old man had steroid-dependent ulcerative colitis. Leukocytapheresis
      (LCAP) was carried out to induce remission, but soon hematuria and renal
      dysfunction appeared. Since he had no autoimmune hemolytic anemia, and there was
      no possibility of his having had hemolytic uremic syndrome, it was considered
      that this hemolysis could have been caused by mechanical stimulation on the LCAP
      column, and then the hemolysate flowed into his body. We should be aware that
      hematuria might occur as a side effect of LCAP.

PMID- 17023756
TI  - [A case of endocrine cell carcinoma of the ileum: sonographic findings and
      clinical outcome].
AB  - A 56-year-old man, who had been complaining of diarrhea for several months, was
      admitted for further examination of a hepatic tumor. A needle biopsy of the
      hepatic tumor suggested metastatic carcinoid tumor. The primary tumor was found
      in the ileum by extracorporeal sonographic examination and a barium meal study.
      We performed a partial excision of the ileum, lymph node resection, wedge biopsy
      of the liver, and catheterization from the right iliac artery to the hepatic
      artery for intraarterial chemotherapy. The pathological diagnosis was endocrine
      cell carcinoma of the ileum and local lymph nodes and hepatic metastasis. After
      surgery, the patient has been treated with continuous intraarterial infusion of
      CDDP and 5FU. The liver tumors almost disappeared. As of 20 months after the
      surgery, the patient is well and is being followed in the outpatient clinic.

PMID- 17023757
TI  - [Two cases of intractable hepatic hydrothorax successfully treated with nasal
      CPAP].
AB  - Hepatic hydrothorax is often resistant to various treatments. A failure in the
      treatment for hepatic hydrothorax may be associated with poor prognosis. We
      report two cases of intractable hepatic hydrothorax successfully treated by
      combining chemical pleurodesis using OK-432 with nasal continuous positive airway
      pressure. Combination therapy may provide a minimally invasive and effective
      treatment for intractable hepatic hydrothorax.

PMID- 17023758
TI  - [A case of relapsed ischemic colitis with colon cast-like stripped mucosa].
AB  - An 82-year-old woman who had 5 relapses of ischemic colitis was admitted with
      sudden lower abdominal pain. Colonoscopic examination performed on the 2nd day
      revealed colon cast-like stripped colonic mucosa in the lower portion of the
      descending colon. She was treated conservatively. After 2 weeks, ischemic colitis
      healed, with slight residual stenosis. Most reports of colon cast indicated that
      colon cast was caused by abdominal aneurysm, operation, or external wound. The
      only predisposing conditions in this case were arteriosclerosis of abdominal
      aorta and chronic constipation. Arteriosclerosis and chronic constipation might
      be the important risk factors of ischemic colitis with colon cast and relapsing
      of ischemic colitis.

PMID- 17023759
TI  - [A case of gallstone ileus which the cholecystoduodenal fistula closed
      spontaneously after laparoscopic-assisted simple enterolithotomy].
AB  - A 47-year-old woman complaining of diarrhea and vomiting was admitted on the
      suspicion of gallstone ileus 4 days after onset. Upper gastrointestinal
      radiography by Gastrografin showed a cholecystoduodenal fistula. Laparoscopic
      assisted simple enterolithotomy was performed. The omentum was severely adherent
      to the gall bladder and fistula, though biliary surgery was not performed.
      Without second look operation, for cholecystoduodenal fistula closed
      spontaneously.

PMID- 17023760
TI  - [A case of recurrent biliary cystadenocarcinoma successfully treated with
      5FU/CDDP systemic chemotherapy].
AB  - We report a case of biliary cystadenocarcinoma which recurred 41 months
      postoperatively. A 60-year-old woman was admitted for further examination of
      multiple metastatic tumors and a large amount of ascites. Systemic administration
      of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed
      tomography revealed considerable reduction of the metastatic tumors and ascites.
      Since her general condition had improved, chemotherapy was continued in the
      outpatient clinic.

PMID- 17023761
TI  - [A case of the extrahepatic bile duct carcinoid tumor].
AB  - A 76-year-old man presented with back discomfort and jaundice. CT and MRI of the
      abdomen revealed a mass in the common bile duct. Cytology of the bile juice
      obtained by percutaneous transhepatic cholangio-drainage revealed class V. The
      patient underwent laparotomy and pancreatoduodenectomy. Pathology showed a
      carcinoid tumor of the biliary tract, 14 x 10 mm in size. Grimelius staining
      demonstrated the presence of argyrophilic granules. On immunochemistry, the tumor
      stained positive for chromogranin A and synaptophysin. He had two liver
      metastases 8 months postoperatively.

PMID- 17023762
TI  - Primary and secondary patency rates and complications of upper extremity
      arteriovenous fistulae created for hemodialysis.
AB  - The types of fistulae used and their complication rates are important for the
      hemodialysis patients. We aimed to compare retrospectively the primary and
      secondary patency rates and complications of upper extremity arteriovenous
      fistulae. Between 1984 and 2005, a total of 1,233 upper extremity arteriovenous
      fistulae were created in 920 patients. The mean age was 42 +/- 21 years. The
      fistulae were divided into the 3 groups; 588 radiocephalic, 205 brachiocephalic,
      and 127 were created by polytetrafluoroethylene graft. The fistulae types were
      evaluated with regard to their primary-secondary patency rates and complications.
      There was a significant difference with regard to development of thrombosis in
      radiocephalic group compared to other two groups, respectively, p = 0.0122, p =
      0.0091. In brachiocephalic fistulae group, edema and steal phenomenon were
      statistically significant (p < 0.0001). The aneurysm formation was statistically
      significant in polytetrafluoroethylene fistulae graft group (p < 0.0001). During
      6 months, 2 and 5 years period, while primary patency rate was higher in three
      fistulae types, in radiocephalic fistulae both primary and secondary fistulae
      patency rates were lower (p < 0.05). To create successful arteriovenous fistulae
      with long-term patency, appropriate veins of patients should be carefully
      preserved; thus initially a distal site should be preferred, and in case of
      failure the next fistulae should be created proximally. In case of failure of
      forearm fistulae, primary fistulae with autogenous veins should be tried at the
      upper arm first, and if this also fails, fistulae formation with synthetic grafts
      should be considered.

PMID- 17023763
TI  - Construct validity of the Frenchay Activities Index for community-dwelling
      elderly in Japan.
AB  - Many researchers have developed various measures to evaluate the functional
      status of community-dwelling elderly. The Frenchay Activities Index (FAI) was
      developed to measure instrumental activities of daily living in stroke
      populations. The FAI has undergone the most intensive evaluation, but its factor
      structure has not been examined in Japan. The primary purpose of this study was
      to investigate the construct validity of the FAI for non-stroke community
      dwelling elderly in Japan. The study subjects were 1,323 randomly selected
      community older residents in Hojo city, Ehime prefecture, the southern part of
      Japan. In order to investigate the construct validation, we performed factor
      analyses, i.e., exploratory factor analysis and confirmatory factor analysis.
      Furthermore, we examined the influences of age and gender on the FAI constructs.
      In the results, the FAI had a two-factor structure consisting of domestic chores,
      including washing clothes and preparing meals, and work and leisure, including
      gardening, driving and outings. Younger age was significantly related to
      increased performance on both factors. In addition, relative to females, males
      had a lower performance on the domestic chores and a greater performance on the
      work and leisure. These results suggest that the FAI satisfies the construct
      validity in the Japanese community-dwelling elderly. The FAI and its two factors
      provide important and clinically valuable information for understanding the
      patterns of functional status in the Japanese community-dwelling elderly.

PMID- 17023764
TI  - Association between the polymorphism of the angiotensin-converting enzyme gene
      and tumor size of breast cancer in premenopausal patients.
AB  - The association between the polymorphism of the angiotensin-converting enzyme
      (ACE) gene and breast cancer risk has been extensively studied, however, the
      studies about the prognostic factors and ACE gene polymorphism are limited in
      number. Our aims were to analyze the distribution of the insertion/deletion (I/D)
      polymorphism of the ACE gene in Turkish premenopausal patients with breast
      cancer, which is more aggressive than the postmenopausal counterpart, and to
      assess whether DD genotype is associated with poor prognostic factors. The DD
      genotype has been shown to be associated with the increased serum and tissue
      levels of ACE, compared to those in II and ID genotypes. ACE genotypes were
      determined by polymerase chain reaction in 44 Turkish premenopausal patients with
      breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes
      are distributed in patients and control subjects as follows; DD is present in 25
      (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID
      in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I
      alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in
      healthy subjects, respectively. In breast cancer patients, no significant
      association was observed between the ACE genotypes and poor prognostic factors,
      such as negative hormone receptor status, histological grade, lymph node
      involvement, higher number of lymph node metastases, and c-erb B2 overexpression,
      except that tumor size greater than 2 cm is associated with DD genotype (p =
      0.02). Thus, ACE may influence the local tumor growth of breast cancer in
      premenopausal patients.

PMID- 17023765
TI  - Exhaustive exercise induces differential changes in serum granulysin and
      circulating number of natural killer cells.
AB  - The circulating number of natural killer (NK) cells largely changes after an
      acute bout of physical exercise. Granulysin is a cytolytic granule protein with a
      broad range of antimicrobial and tumoricidal activities produced and released by
      human NK cells and cytolytic T lymphocytes. Since NK cells constitutively produce
      granulysin, most serum granulysin in healthy humans is derived from NK cells.
      Serum graulysin levels in the healthy humans may therefore reflect the size of
      whole-body NK cell population in the body. The aim of this study was to determine
      the effect of an acute bout of exhaustive exercise on serum granulysin in
      comparison with the circulating number of NK cells. Six healthy, young male
      volunteers participated in the study. Each subject underwent both exhaustive
      exercise and resting sessions in a random order with at least a seven-day
      interval. Subjects were asked to run to exhaustion on a treadmill with an
      incremental graded protocol. Blood samples were collected before, immediately
      after, and 1 hr, 3 hr, 6 hr, 12 hr and 24 hr after exercise. Serum granulysin
      levels were measured by enzyme-linked immunosorbent assay (ELISA). NK cells were
      determined by flow cytometry. Exhaustive exercise induced a 4.8-fold increase in
      peripheral blood NK cells, but no significant change in serum granulysin. Our
      results support the hypothesis that exhaustive exercise-induced changes in the
      circulating number of NK cells represent a redistribution of lymphocytes, rather
      than the change in the size of whole-body NK cell population.

PMID- 17023766
TI  - Early detection of plasma cytomegalovirus DNA by real-time PCR after allogeneic
      hematopoietic stem cell transplantation.
AB  - Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality
      after allogeneic hematopoietic stem cell transplantation. Therefore, preemptive
      ganciclovir therapy based on early detection of CMV reactivation is widely used
      to prevent CMV disease. Real-time polymerase chain reaction (PCR) has been widely
      used for monitoring CMV reactivation as well as the antigenemia assay that
      detects CMV structural phosphoprotein with a molecular weight of 65,000 (pp65).
      We developed a real-time PCR assay system for CMV based on a double-stranded DNA
      specific dye, SYBR Green I, and quantified DNA, which was extracted automatically
      from plasma. This real-time PCR assay and the pp65 antigenemia assay were
      compared in parallel with 357 blood samples obtained from 64 patients who
      underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Real
      time PCR assay results correlated with those of the pp65 antigenemia assay (p <
      0.0001). It is noteworthy that the detection of CMV DNA by PCR preceded the first
      positive antigenemia by 14 days. In this study, 10 of 64 patients developed CMV
      disease. The antigenemia assay detected CMV reactivation earlier than the
      development of CMV disease only in four of 10 patients. In contrast, our real
      time PCR detected CMV-DNA before the development of CMV diseases in eight of 10
      patients. The real-time PCR with SYBR Green I as a detection signal is simple and
      readily performed, and may be a useful system for early detection of CMV
      reactivation after allo-HSCT.

PMID- 17023767
TI  - Correlation of abnormal mitochondrial distribution in mouse oocytes with reduced
      developmental competence.
AB  - Selection of good quality oocytes is important for improvement of assisted
      reproductive technology. Here, we studied the relationship of the mitochondrial
      distribution in metaphase II stage (MII) oocytes with fertility, since
      mitochondria in ooplasm are essential for energy production required for
      fertilization and embryo development. To observe mitochondria non-invasively, we
      used oocytes from a transgenic mouse, in which enhanced green fluorescent protein
      is targeted to the mitochondrial matrix and thus fluorescence is observed
      exclusively in the mitochondria. Control oocytes with mitochondria distributed
      around the nucleus showed normal embryo developmental competence, whereas oocytes
      with abnormal diffuse and fragmented mitochondria showed a significantly lower
      rate of embryo development after activation by intracytoplasmic sperm injection
      or strontium, which is a very effective agent for activation of mouse oocytes.
      Also, we showed that the reduced developmental competence of oocytes with diffuse
      and fragmented mitochondria caused by vitrification and thawing is similar to
      that of oocytes with abnormal mitochondrial foci obtained naturally. These
      findings suggest that abnormal mitochondrial distribution in oocytes at MII is a
      cause of developmental retardation and therefore normal mitochondrial
      distribution could be used as a criterion for selection of good oocytes.

PMID- 17023768
TI  - Agmatine suppresses mesangial cell proliferation by modulating polyamine
      metabolism.
AB  - Polyamines play an essential role in the growth and differentiation of mammalian
      cells. The depletion of intracellular polyamines results in the suppression of
      growth. Proliferation of glomerular mesangial cells (MC) is the most common
      pathologic change in many forms of glomerulonephritis. Agmatine is a metabolite
      of arginine via arginine decarboxylase (ADC), highly expressed in the kidney, and
      unique in its capacity to suppress intracellular polyamine levels required for
      proliferation. As agmatine enters mammalian cells via the polyamine transport
      system, its antiproliferative effects may preferentially target cells with
      increased proliferative kinetics. In the present study, we evaluated the
      antiproliferative effects of agmatine on human MC in vitro. MC proliferation was
      stimulated with 20% fetal bovine serum (FBS) or platelet-derived growth factor
      (PDGF-BB, 20 ng/ml). Cell proliferation was measured using the (4.3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) proliferation
      assay. Intracellular polyamine levels were assayed by high performance liquid
      chromatography, and cell death was assessed by cellular DNA fragmentation enzyme
      linked immunosorbent assay. The MTT proliferation assay showed that agmatine
      significantly suppressed proliferation of human MC treated with 20% FBS or 5% FBS
      + PDGF as compared to human MC treated with 5% FBS. Polyamine levels were
      markedly lower in cells treated with agmatine, and proliferation was rescued by
      administration of putrescine. The fragmented DNA was hardly detected in agmatine
      treated human MC. In summary, human MC stimulated to increase their proliferative
      kinetics are significantly more sensitive to the antiproliferative effects of
      agmatine than normally cultured cells. Suppressed proliferation of the agmatine
      treated human MC is not due to increased cell death. These results suggest that
      agmatine is a promising drug candidate for the treatment of human mesangial
      proliferative glomerulonephritis.

PMID- 17023769
TI  - Hemodynamic and anesthetic advantages of dexmedetomidine, an alpha 2-agonist, for
      surgery in prone position.
AB  - The alpha2-agonist dexmedetomidine (Dex), a sedative and analgesic, reduces heart
      rate (HR) and blood pressure, and has been used in the practice of anesthesia. In
      this study, we aimed to evaluate the effects of Dex on hemodynamic variables,
      anesthetic sparing effects, and recovery profiles in patients who underwent
      surgery in prone position. The prone position itself can cause a decrease in the
      systemic blood pressure. Forty patients who undergo lumbar discectomy were
      randomly assigned to receive either Dex (a loading dose 1 microg/ kg in 10
      minutes followed by an infusion rate of 0.2 microg/ kg/ hr) or saline. In both
      groups, the anesthesia was induced with fentanyl, thiopental and rocuronium, and
      maintained with desflurane in 50% N(2)O. Mean arterial blood pressure (MAP), HR,
      cardiac output (CO), and level of anesthesia were monitored. Recovery times and
      analgesic requirements were also recorded. As a response to endotracheal
      intubation, a significant increase in MAP and HR was observed in the control
      group compared to the Dex group, but no difference in CO. The recovery times were
      significantly shorter in the Dex group compared to the control group. Anesthetic
      and analgesic requirements of the Dex group were lower than controls. Thus, the
      use of Dex caused no detrimental effects on the hemodynamic variables in prone
      position. In addition, Dex decreased pressure response to intubation, and
      anesthetic and analgesic requirements, shortened recovery times, and decreased
      postoperative pain level. Dex may be an alternative to currently used adjunctive
      anesthetic agents in lumbar discectomy operations.

PMID- 17023770
TI  - Schwannoma of the retropharyngeal space.
AB  - We report a rare case of schwannoma arising from the retropharyngeal space. A 24
      year-old man presented a 2-month-history of a foreign body sensation in the
      throat and gradually progressing dysphagia when he swallowed solids and liquids.
      The patient had no odynophagia, fever, or blood in his saliva. Computed
      tomographic scans and magnetic resonance images revealed a well-defined and oval
      mass, measuring about 40 mm x 20 mm in size, in the retropharyngeal space.
      Because the tumor existed in the retropharyngeal space and was the adequate size,
      the patient underwent trans-oral resection under the direct laryngoscope without
      the need for skin incision. On the basis of the histological findings, the tumor
      was diagnosed as a schwannoma. It was mostly composed of spindle cells arranged
      in short bundles and fascicles, with focal palisading of the nuclei. The neoplasm
      arising from the retropharyngeal space is quite rare, because of few anatomical
      structures in the space. The post-operative course was uneventful, and the
      patient is currently free from disease 30 months after surgery. Diagnosis,
      clinical behavior, and treatment of retropharyngeal schwannoma are reviewed from
      perusal of the literature. When schwannomas are located in the pharynx, they may
      cause foreign body sensation or dysphagia. Therefore, when a foreign body
      sensation in the larynx is present, a thorough diagnostic procedure should be
      performed to evaluate the morphology of the upper aerodigestive tract.

PMID- 17023771
TI  - Treatment of idiopathic gustatory rhinorrhea by resection of the posterior nasal
      nerve.
AB  - We herein describe a case of 44-year old female who presented with a chief
      complaint of gustatory rhinorrhea from childhood, in which gustatory stimuli
      caused bilateral excessive, watery nasal secretion. No abnormality of taste
      acuity was observed. This disorder was presumably caused by faulty regenerated
      parasympathetic nerve fibers reaching the nasal mucosa or possibly, by a
      congenital condition. Nasal pretreatment with an anti-cholinergic drug clinically
      blocked the positive sugar-induced rhinorrhea, thus indicating that the gustatory
      rhinitis in this case was produced by foods that stimulate muscarinic receptors
      sensitive to atropine (probably on submucosal nasal glands). Although this
      syndrome can be treated prophylactically by the use of topical atropine, the
      patient preferred to undergo radical therapy and a resection of the posterior
      nasal nerve was performed through the middle meatus under endoscopic control. The
      resection of the nerve on both sides resulted in an almost complete inhibition of
      the sugar-induced rhinorrhea without serious complications. Although this disease
      is not life-threatening, it is socially embarrassing and troublesome to patients
      and surgical therapy is one of the accepted modalities.

PMID- 17023772
TI  - Enhanced perfusion in eyes and cerebral perfusion defects in a patient with
      Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) is known as the most common form of inherited mental
      retardation. In our study, brain perfusion single photon emission computed
      tomography (SPECT) was performed in a 6 year-old boy diagnosed with FXS. Diffuse
      bilateral uptake of Technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO)
      was noted in his orbits, as well as cortical perfusion defects (hypoperfusion in
      the right parietal and the left temporal lobe). Ophthalmologic examination showed
      no pathological findings. Magnetic resonance imaging (MRI) revealed no
      abnormality in the orbital structures, although hypoplasia of cerebellum and
      vermis was visualized. Since the patient was crying during the injection, the
      increased blood flow or the increased metabolism of the eyes and/or ocular
      muscles may be responsible for this orbital finding. Alternatively, the enhanced
      uptake of HMPAO in the orbits may reflect the pathology associated with FXS,
      because patients with FXS might have visual-motor abnormalities. To the best of
      our knowledge, there has been no report documenting such an orbital uptake of
      HMPAO. Moreover, the visualization of decreased cerebral perfusion, with the
      normal findings of MRI, indicates that brain SPECT imaging with HMPAO is helpful
      for detecting brain abnormalities in children with FXS.

PMID- 17023773
TI  - On the future of radiation therapy.

PMID- 17023774
TI  - Preoperative radiotherapy alone or combined with chemotherapy followed by
      transanal excision for rectal adenocarcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of preoperative radiotherapy (RT) and
      chemoradiation (CRT) followed by transanal excision (TAE) for rectal
      adenocarcinoma. METHODS: Thirty-two patients were treated between July 1988 and
      April 2004 and followed from 2 to 123 months (median, 27 months). RESULTS: The 3
      year outcomes were: locoregional control, 79%; distant metastasis-free survival,
      80%; cause-specific survival, 88%; and overall survival, 75%. Outcomes were
      better for patients with T1-T2 tumors and those who experienced a complete
      response to preoperative RT or CRT. Two patients (6%) had chronic RT proctitis
      after treatment. CONCLUSION: A select subset of patients with T2/T3 tumors will
      experience similar outcomes after preoperative RT or CRT and TAE compared with
      radical proctectomy. Reliably predictive clinicopathologic features to define
      this subgroup would best be elicited in the context of large prospective
      randomized trials, as would the optimal combination and schedule of systemic
      agents delivered in conjunction with preoperative RT. Patients who experience a
      complete response (cCR) after preoperative CRT are excellent candidates for TAE;
      those with less than a cCR have a less-favorable prognosis and are probably
      better treated with a low anterior resection or abdominal-perineal resection.

PMID- 17023775
TI  - Phase II trial of preoperative chemoradiation with a hyperfractionated radiation
      boost in locally advanced rectal cancer.
AB  - PURPOSE: The purpose of this phase II study was to prospectively determine the
      efficacy of preoperative chemoradiation with a hyperfractionated (Hfx) RT boost
      to 61.8 Gy in locally advanced rectal cancer. METHODS: Eligibility stipulated
      that the primary lesion had to be either T4; or T3 and >4 cm or 40% of the bowel
      circumference. Radiation (RT) consisted of 45 Gy to the pelvis (1.8 Gy per
      fraction) followed by 1.2 Gy twice daily (to the gross tumor volume) to a total
      RT dose of 61.8 Gy. There was 5-FU infused at 1 g/m2/24 hours for 4 days during
      the 1st and 6th weeks of RT (concurrent with the Hfx boost). Surgical resection
      was planned 4 to 6 weeks later. Adjuvant chemotherapy (bolus 5-FU/leucovorin) was
      scheduled for 4 cycles at 28-day intervals. RESULTS: There were 22 patients, ages
      22 to 81 years (median, 64) enrolled in the study. Of the 20 patients evaluable
      for response, 10 (50%) had evidence of clinical downstaging and 5 patients (25%)
      had > or =90% fibrosis in the resected specimen. With a median f/u of 40 months
      (7-158), the 4 years actuarial rate for all patients (n = 22) of OS was 64%, of
      DFS 62%, and of LC 84%. 3/21 patients (14%) had positive margins, all of whom
      developed a local failure (P < 0.001). CONCLUSION: This regimen of high dose
      preoperative chemoRT with a Hfx RT boost (to 61.8 Gy) in patients with bulky,
      locally advanced rectal cancer results in clinical downstaging in half of the
      patients with significant fibrosis in the operative specimen.

PMID- 17023776
TI  - Hypothyroidism when the thyroid is included only in the low neck field during
      head and neck radiotherapy.
AB  - OBJECTIVE: The minimum dose required to electively irradiate all of part of the
      low neck for squamous cell carcinoma of the oropharynx is 50 Gy in 25 fractions
      or its radiobiological equivalent. The purpose of our study is to determine the
      incidence of hypothyroidism when the thyroid is treated only in the low-neck
      radiotherapy (RT) field to approximately 50 Gy. METHODS AND MATERIALS: 390
      patients with oropharyngeal carcinoma received RT between 1990 and 2000, had no
      prior thyroid disease or surgery, and had RT involving the standard anterior low
      neck field including the thyroid with a dose equivalent to 50 Gy at 2Gy/fx with
      or without a boost to a portion of the field to 60 to 70 Gy. The end point was
      hypothyroidism defined as thyroid stimulating hormone (TSH) above the upper limit
      of the normal range. RESULTS: As we did not routinely monitor TSH during this
      study, it was obtained in 169 of 390 patients. Median follow-up on all 390
      patients was 6.1 years. The incidence of hypothyroidism was calculated for 2
      groups: 169 patients with TSH data and the total population of 390 patients. For
      both analyses, patients were censored at last follow-up if the TSH level was
      normal, or if TSH was not checked. The incidence of hypothyroidism at 5 years was
      31% for all 390 patients and 54% for the subset of 169 patients with TSH data.
      Adjuvant chemotherapy and/or planned neck dissection may be associated with a
      small increased risk of hypothyroidism. CONCLUSIONS: Including the thyroid in the
      low-neck field to 50 Gy results in hypothyroidism in 30% to 50% of patients at 5
      years, suggesting that the threshold for this complication is <50 Gy.

PMID- 17023777
TI  - Radiation rescue for biochemical failure after surgery for prostate cancer:
      predictive parameters and an assessment of contemporary predictive models.
AB  - OBJECTIVES: To determine pretreatment prognostic variables that predict outcome
      of radiotherapy for biochemical failure after prostate cancer surgery and
      evaluate contemporary clinical decision tools for patient selection. METHODS:
      Fifty patients were identified with failure after rescue radiation was defined as
      a confirmed rise in PSA, distant metastases, prostate cancer death, or initiation
      of hormonal therapy. Univariate analysis and multivariate Cox models were
      constructed. Outcome was compared with decision tree and recursive partitioning
      predictive models. RESULTS: The median preradiation PSA (pre-RT PSA) was 1.2
      ng/mL and the median dose of radiation was 66.6 Gy; median follow-up was 39.6
      months. Overall, the estimated 3-year failure free survival was 54%, 95%CI
      [43,74]. Seminal vesicle involvement (SVI) (P = 0.003) and preradiation PSA
      Doubling Time (PSADT) <10 months (P = 0.01) were both significant predictors for
      treatment failure whereas pre-RT PSA was of borderline significance (P = 0.07).
      On multivariate analysis a pre-RT PSA of >1 and SVI were associated with hazard
      ratios of 6.2 and 7.3 (P = 0.01 and P = 0.004), respectively. An additional Cox
      model constructed for 31 patients for whom pre-RT PSADT could be calculated
      showed PSADT and SVI to be independent prognostic parameters. Two predictive
      models, a decision tree analysis, and a recursive partitioning model were
      moderately accurate in predicting outcome in this series, however, high-risk
      patients experienced less treatment failures than predicted. CONCLUSIONS: Pre-RT
      PSA <1 ng/mL, longer PSADT (>10 months) and no SVI are associated with improved
      outcome after rescue radiation. Contemporary clinical prediction tools are
      imperfect predictors of outcome for rescue radiation therapy.

PMID- 17023778
TI  - Matched-pair analysis of prostate cancer patients with a high risk of positive
      pelvic lymph nodes treated with and without pelvic RT and high-dose radiation
      using high dose rate brachytherapy.
AB  - OBJECTIVE: Adding pelvic radiation to high-dose prostate radiation for prostate
      cancer patients with a >15% risk of positive lymph nodes (LN) is controversial.
      We performed a matched-pair analysis of patients treated at 2 institutions to
      assess the impact of pelvic radiotherapy (P-RT). METHODS: From January 1993 to
      March 2003, 2 institutions treated 1432 prostate cancer patients with combined
      external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy. Those
      receiving EBRT were treated either to the prostate and seminal vesicles alone or
      to the entire pelvis (46 Gy). In all cases, prostate dose (EBRT and HDR) resulted
      in an average BED >100 Gy (alpha/beta = 1.2). There were 755 cases identified as
      having a pelvic LN risk >15% using the Roach formula. Of these, 255 cases were
      treated without pelvic RT and randomly matched by Gleason score, T stage, and
      pretreatment PSA to 500 cases treated with pelvic RT, resulting in 250 pairs
      (1:1). RESULTS: Median follow-up was 4.0 years (P = 0.7). The 4-year prostate
      biochemical failure (22% versus 14%, P = 0.12), distant metastasis (9% versus 4%,
      P = 0.6), event-free survival (72% versus 78%, P = 0.3), prostate cancer death
      rate (4% versus 2%, P = 0.9), and overall survival (89% versus 88%, P = 0.7) were
      not significantly different for patients treated with and without P-RT. Analysis
      with and without androgen deprivation therapy showed similar results. CONCLUSION:
      Improved biochemical, clinical, or survival outcomes were not observed for
      prostate cancer patients at risk for positive pelvic LN >15% when treated with
      high-dose EBRT and HDR brachytherapy to the prostate with or without pelvic
      radiation.

PMID- 17023779
TI  - A prostate specific antigen (PSA) bounce greater than 1.4 ng/mL Is clinically
      significant after external beam radiotherapy for prostate cancer.
AB  - OBJECTIVE: The purpose of this report is to determine whether any specific
      magnitude in the prostate specific antigen (PSA) bounce predicted for a
      clinically poorer outcome. METHODS AND MATERIALS: Between May 1989 and August
      1999, 568 prostate cancer patients were treated with 3-dimensional conformal
      radiotherapy (RT). All patients had at least 5 years of follow up, 6 post-RT PSA
      measurements and received no hormonal therapy as part of their initial
      management. The median follow up was 85 months. The median RT dose was 74 Gy. A
      bounce was defined by a minimum rise in PSA of 0.4 ng/mL over a 6-month period,
      followed by a drop of PSA of any magnitude. The analysis of the optimal PSA
      bounce cut-point was based upon a recursive partitioning approach (RPA) for
      censored data using the log-rank test for nodal separation of freedom from
      biochemical failure (FFBF) as defined by the American Society for Therapeutic
      Radiology and Oncology (ASTRO) definition. Cox multivariate regression analysis
      (MVA) was used to confirm independent predictors of outcome among clinical and
      treatment related factors: PSA bounce as defined by the RPA, pretreatment PSA
      (continuous), Gleason score (2-6 versus 7-10), T stage (T1c/T2ab versus T2c/T3),
      and total radiation dose (continuous). RESULTS: There were 154 patients (27%)
      experienced a bounce with a median magnitude of 0.6. The RPA resulted in an
      optimal PSA bounce cut-point of 1.4 ng/mL such that 5-year Kaplan-Meier estimates
      of FFBF were 71%, 59%, and 38% for nonbouncers, a bounce < or =1.4 ng/mL and >1.4
      ng/mL, respectively. Twenty-one (14%) of the 154 patients who experienced a
      bounce had a PSA bounce magnitude >1.4 ng/mL. Stepwise MVA demonstrated that the
      PSA bounce grouped as above was an independent predictor of FFBF (P = 0.0013),
      freedom from distant metastases (P = 0.0028) and cause specific survival (P =
      0.0266). Lower RT dose (P < 0.0001) was the only independent predictor of a PSA
      bounce >1.4 ng/mL. CONCLUSIONS: Using recursive partitioning techniques, a
      clinically significant PSA bounce occurred when the magnitude of the bounce was
      >1.4 ng/mL. This is important information to aid clinicians in determining
      management after RT.

PMID- 17023780
TI  - Is there a detrimental effect of waiting for radiotherapy for patients with
      localized prostate cancer?
AB  - OBJECTIVE: To evaluate a possible deleterious effect of waiting time to
      radiotherapy on the biochemical relapse (BR) of patients with localized prostate
      cancer. PATIENTS AND METHODS: Patients included in this retrospective study had
      localized prostate adenocarcinoma treated with external-beam irradiation alone.
      Waiting time was defined as the interval between the first consultation and the
      first radiation treatment. BR was defined as 3 consecutive rises of prostatic
      specific antigen (PSA). Patients were split into 3 groups of waiting time: group
      A were treated within 40 days; group B waited 41 to 80 days; group C waited >80
      days to receive radiotherapy. The effect of waiting on BR was estimated by the
      Kaplan-Meier method. Multivariate Cox proportional hazards modeling was adjusted
      for known prognostic factors. RESULTS: There were 289 patients who participated
      in the analysis. Median follow-up time was 6.1 year. Overall BR rate was 44% at 5
      years. The median waiting time increased over the study period from 26 days in
      1992 to 123 days in 2000. In adjusted multivariate analysis there was a
      nonsignificant higher risk of BR with waiting for 41 to 80 days (hazard ratio
      [HR] = 0.8; 95% confidence interval [CI] = 0.3-1.6) and for >80 days (HR = 0.6;
      95% CI = 0.2-1.5) when compared with patients treated within 40 days after
      consultation. CONCLUSION: Delaying the start of radiotherapy showed little effect
      on the rate of BR in the group of 288 prostate cancer patients analyzed in this
      study.

PMID- 17023781
TI  - The use of complementary and alternative medicine by cancer patients undergoing
      radiation therapy.
AB  - OBJECTIVE: Use of complementary alternative medicine (CAM) is widespread among
      patients with chronic diseases including cancer. The purpose of our study was to
      examine the pattern of alternative medicine use in patients undergoing radiation
      treatment of cancer. METHODS AND MATERIALS: A cross-sectional study was conducted
      among cancer patients treated with radiation therapy from July 2003 through July
      2005 at the University of Cincinnati. We defined CAM as the use of dietary
      supplements, massage therapy, prayer, acupuncture, chiropractic, and other novel
      therapies undertaken after their diagnosis with cancer. RESULTS: There were 152
      patients that participated in the study. Their median age was 59 (range, 21-85),
      82 (54%) were males, 108 (69%) were Caucasian. Out of 152 patients, 104 (68%)
      patients were users of CAM. The most common CAM modality reported was prayer 85
      (82%) and use of dietary supplements 84 (80%). The majority of users were female
      and well-educated. Among CAM users 60 (58%) had discussed its use with their
      physician. Level of education, employment status and income showed a significant
      correlation with the use of CAM. CONCLUSION: This study demonstrates that the use
      of complementary alternative medicine among cancer patients receiving radiation
      therapy is frequent. Given the potential risks with some CAM therapies,
      physicians should actively ask patients whether they use CAM and provide
      appropriate counseling.

PMID- 17023782
TI  - Three-dimensional conformal external beam radiotherapy (3D-CRT) for accelerated
      partial breast irradiation (APBI): what is the correct prescription dose?
AB  - OBJECTIVE: This study is an evaluation of the biologic equivalence of the dose
      prescriptions for brachytherapy and 3-dimensional conformal external beam
      radiotherapy (3D-CRT) accelerated partial breast irradiation (APBI), using actual
      patient dose matrix data, and is based on the concept of equivalent uniform
      biologically effective dose (EUBED). This formalism allows a nonuniform dose
      distribution to be reduced to an equivalent uniform dose, while also accounting
      for fraction size. MATERIALS AND METHODS: Five computed tomography scans were
      selected from a group of patients treated with multicatheter interstitial APBI.
      Dose matrices for the brachytherapy plans were computed and analyzed with in
      house software. For each patient, the EUBED for the brachytherapy dose matrix was
      generated based on calculations performed at the voxel-level. These EUBED values
      were then used to calculate the biologically equivalent fraction size for 3D-CRT
      (eud). RESULTS: The mean equivalent fraction size (eudmean) and maximum
      equivalent fraction size (eudmax) were calculated for each patient using 100
      different values of the alpha/beta ratio. The eudmean ranged from 3.67 to 3.69
      Gy, while the eudmax ranged from 3.79 to 3.82 Gy. For all values of the
      alpha/beta ratio, the maximum fraction size calculated to deliver a biologically
      equivalent dose with 3D-CRT was 3.82 Gy, with an equivalent total prescription
      dose of 38.2 Gy. CONCLUSION: Utilizing a wide range of established
      radiobiological parameters, this study suggests that the maximum fraction size
      needed to deliver a biologically equivalent dose using 3D-CRT is 3.82 Gy,
      supporting the continued use of 3.85Gy BID in the current national cooperative
      trial.

PMID- 17023783
TI  - Computed tomography (CT) scan evaluation of late toxicity following
      hypofractionated/accelerated radiotherapy with cytoprotection (HypoARC) in breast
      cancer patients treated with conservative surgery.
AB  - BACKGROUND: In the present study we evaluated the long-term radiation toxicity of
      an hypofractionated accelerated radiotherapy scheme supported with amifostine
      cytoprotection (hypoARC). PATIENTS AND METHODS: A cohort of 32 breast cancer
      patients, pretreated with conservative surgery and adjuvant doxorubicin or taxane
      based chemotherapy, were treated with hypoARC. In contrast to the 45 days
      required for the delivery of standard breast (+/-supraclavicular) radiotherapy,
      the proposed scheme delivers the whole radiation dose in 16 days (10 fractions of
      3.5Gy plus 2 additional 4Gy fractions to the tumor bed), which is convenient for
      elderly patients or patients residing away from radiotherapy departments.
      RESULTS: After a minimum follow up of 24 months (range, 24-36), none of the
      patients showed any clinical signs of lung or arm toxicity. Increased palpable
      breast density was evident 16 out of 32 cases. Computed tomography (CT) scan
      evaluation of the lung and breast densities (calculated in Haunsfield units)
      showed no signs of lung fibrosis, while increased density of the irradiated
      breast (1.1-1.3-fold) was confirmed in 8 out of 17 patients examined. None of the
      patients has relapsed locally. CONCLUSIONS: Although longer follow-up is required
      to confirm safety of the described radiotherapy regimen, these data are
      encouraging as the toxicity reported within 2 to 3 years of follow-up is even
      lower than the one expected from standard radiotherapy.

PMID- 17023784
TI  - A phase II study of docetaxel, doxorubicin, and infusional 5-fluorouracil in the
      treatment of patients with locally advanced breast cancer.
AB  - OBJECTIVE: The primary aim of this study was to estimate the rate of clinical and
      pathologic response to preoperative docetaxel, doxorubicin, and infusional 5
      fluorouracil in patients with locally advanced breast cancer. Secondary objective
      included the determination of toxicity profile. PATIENTS AND METHODS: Thirty-nine
      patients (median age 49 years) with histologically confirmed locally advanced
      breast cancer (stage IIIA or IIIB) were studied. Patients received 4 courses of
      chemotherapy with docetaxel (75 mg/m2 iv over 1 hour), doxorubicin (50 mg/m2 iv
      bolus), and 5-fluorouracil (300 mg/m2/d as continuous iv infusion on days 1-5).
      Treatment cycles were repeated every 21 days. Prophylactic filgastrim 5 microg/kg
      s/c QD was administered to all patients. Definitive surgery was performed after
      the completion of 4 cycles of therapy. Pathologic complete response was defined
      as the absence of invasive cancer in both the breast and ipsilateral axillary
      lymph nodes. RESULTS: The clinical objective response rate (partial plus
      complete) was 87% (95% confidence interval [CI]: 76-98%). Three patients (8%) had
      complete pathologic response. Two patients progressed preoperatively. Thirteen
      patients (33%) developed neutropenic fever. Fifty-three percent of the patients
      were hospitalized for treatment related complications. No cardiotoxicity or
      treatment related deaths were observed. CONCLUSIONS: Triple cytotoxic therapy
      based on concurrent doxorubicin and docetaxel with infusional 5-flourouracil (5
      FU) does not appear to significantly improve the pathologic response in patients
      with locally advanced breast cancer.

PMID- 17023785
TI  - Gemcitabine and oxaliplatin in patients with metastatic breast cancer resistant
      to or pretreated with both anthracyclines and taxanes: clinical and
      pharmacokinetic data.
AB  - OBJECTIVES: To evaluate the efficacy, the toxicity and the pharmacokinetics of a
      gemcitabine (GEM) and oxaliplatin (OXA) combination in metastatic breast cancer
      patients (MBC), previously treated with anthracycline and taxanes. METHODS: A
      total of 40 women were enrolled; 37 patients had visceral metastases as dominant
      site of disease, including 20 patients with liver metastases and 14 with multiple
      visceral metastases. Three patients received neo-adjuvant chemotherapy, 13
      patients adjuvant chemotherapy alone, 24 patients chemotherapy for MBC alone.
      Gemcitabine was given at 1000 mg/m2 on days 1, 8 followed by oxaliplatin at 100
      mg/m2 iv on day 2 every 2 weeks (GEM-OXA sequence). Possible pharmacokinetic
      interactions were studied in 10 patients, by administering on cycle 1 gemcitabine
      d1/oxaliplatin d2 (GEM-OXA) and on cycle 2 oxaliplatin d1/gemcitabine d2 (OXA
      GEM). RESULTS: After a median of 8 cycles, 10 partial response (PR) (25%), 16
      stable disease (SD) (40%), and 14 progressive disease (PD) (35%) were obtained.
      The median duration of response was 6 months (3-9) for responding patients and
      4.9 months (2-7.5) for patients with stable disease. For PR, SD and PD patients,
      median survival was 18 (10-23+), 13 (8-18), and 6 months (4-13), respectively. G3
      4 neutropenia occurred in 20% of patients (febrile G3 neutropenia in 2.5%), G3-4
      thrombocytopenia and anemia in 15% and 7.5%. The most frequent G3-4
      nonhematologic toxicity was represented by peripheral neuropathy (20%), always
      reversible. The GEM-OXA and OXA-GEM schedules showed a similar pharmacokinetic
      behavior, with no sequence-dependent interaction. CONCLUSIONS: The combination
      gemcitabine plus oxaliplatin has moderate activity in anthracycline and taxanes
      resistant/relapsed heavily treated patients, mild toxicity and no administration
      sequence-dependent pharmacokinetic interactions.

PMID- 17023786
TI  - Clinical outcomes after reirradiation of paraspinal tumors.
AB  - OBJECTIVE: We present our experience with reirradiation of locally recurrent
      paraspinal tumors using image-guided intensity modulated radiotherapy (IG-IMRT).
      METHODS: We performed a retrospective review of 37 patients who were reirradiated
      using IG-IMRT for recurrent paraspinal tumors between 2000 and 2005. We evaluated
      radiation dose to the spinal cord or cauda equina in first and second radiation
      treatments, time to first recurrence, and clinical outcomes after reirradiation
      including second recurrence, survival, pain, functional status, and toxicity.
      RESULTS: Median time to local failure after first radiation was 13 months. All
      patients underwent salvage reirradiation, postoperatively or with IG-IMRT alone.
      Median radiation dose to the planning target volume (PTV) was 2000 cGy; median
      spinal cord or cauda equina dose was 990 cGy. Median cumulative spinal cord or
      cauda equina dose was 4198 cGy. Local control probability at a median follow-up
      of 8 months was 60%; median interval to second failure was 13 months. Survival
      probability at a median follow up of 12 months was 72%; median survival was 18
      months. Thirty-four patients (91%) reported stable or improved pain after second
      radiation, and 26 (70%) had a stable or improved functional status. Mild acute
      toxicity occurred in 3 patients (8%). No long-term toxicity has been identified.
      CONCLUSIONS: Reirradiation using IG-IMRT is safe and achieves a meaningful
      interval of local control with improved symptoms. Further studies with more
      patients and longer follow up are needed to evaluate toxicity, predictors of
      failure, and timing of radiation after surgical salvage.

PMID- 17023787
TI  - Phase II study of 3-week scheduling of irinotecan in combination with cisplatin
      in patients with advanced nonsmall-cell lung cancer.
AB  - OBJECTIVES: The combination of irinotecan and cisplatin given every 4 weeks is
      one of the standard treatments for advanced nonsmall-cell lung cancer (NSCLC) in
      Japan. The purpose of this study is to evaluate the efficacy, safety and dose
      intensity as a measure of the feasibility of 3-week scheduling of irinotecan and
      cisplatin in patients with advanced NSCLC in phase II study. METHODS: Previously
      untreated patients with stage IIIB and IV NSCLC were treated intravenously with
      irinotecan (60 mg/m2) on days 1 and 8 and cisplatin (60 mg/m2) on day 1 of a 3
      week cycle. RESULTS: Of the 28 patients enrolled, 27 were evaluable for response
      and toxicity. The response rate was 30% (95% confidence interval, 14-50%). The
      median duration of response was 16 weeks (range, 10-26 weeks). The median
      survival time for all patients was 52 weeks and the 1-year and 2-year survival
      rates were 48% and 29%, respectively. The dose-intensity of irinotecan was 34
      mg/m2/wk (range, 19-40). The major toxicities observed were neutropenia (grade 3,
      30%; 4, 30%), leukopenia (grade 3, 30%), and diarrhea (grade 3, 22%). Other
      toxicities were generally mild. CONCLUSIONS: Three-week scheduling of irinotecan
      and cisplatin is effective and feasible in advanced NSCLC.

PMID- 17023788
TI  - Adjuvant high dose rate brachytherapy in the management of soft tissue sarcoma: a
      dose-toxicity analysis.
AB  - OBJECTIVES: Although brachytherapy has been used in the management of soft tissue
      sarcoma for decades, there is little published data regarding dose and toxicity.
      We performed an interim analysis of our high dose-rate experience to establish
      dosing guidelines. METHODS: We analyzed our first 12 soft tissue sarcoma patients
      treated with high dose-rate brachytherapy as tumor bed boost (in conjunction with
      beam therapy), seeking an association between treatment factors and wound-healing
      complications. In the process of our analysis, we devised a dosimetric method to
      retrospectively quantify delivered dose. Our findings were used to formulate
      dosing guidelines; the first 5 cases treated along these guidelines are also
      presented. RESULTS: Despite the small number of cases, we were able to
      demonstrate a correlation (P < 0.01) between wound healing and brachytherapy dose
      (fractional or total biologically equivalent dose). We found no relationship
      between wound healing and patient age, diabetes, width of excised skin, cross
      sectional area of implant, sequencing of therapy, or surgery-to-brachytherapy
      interval. CONCLUSION: There appears to be a relationship between dose and
      disturbed wound healing that should be respected to avoid unnecessary toxicity.
      An objective technique for defining target volume and quantifying dose is
      proposed for meaningful analysis of dose/effect relationships.

PMID- 17023789
TI  - Are we ducking the issues of aging?

PMID- 17023790
TI  - The role of alpha-blockers in the management of lower urinary tract symptoms in
      prostate cancer patients treated with radiation therapy.
AB  - OBJECTIVE: Radiation therapy (RT) is commonly used for the treatment of prostate
      cancer, either via brachytherapy or external beam, and is often accompanied by
      dose-related obstructive and irritative lower urinary tract symptoms (LUTS). This
      review will analyze the current state of knowledge of LUTS secondary to RT for
      prostate cancer and review treatment options for this complication. METHODS: A
      review of the literature. RESULTS: Radiation-induced effects in the lower urinary
      tract that result in LUTS include injury to peripheral neurons, interstitial
      fibrosis of the bladder, and loss of muscle fibers in the muscularis propria.
      LUTS are associated with a diminished quality of life and impaired sexual
      function. Numerous nonrandomized studies and one randomized study support the
      proposition that the occurrence of LUTS secondary to RT is effectively mitigated
      by alpha1-adrenoreceptor blockade. CONCLUSIONS: Basic and clinical science
      studies as well as clinical guidelines relevant for LUTS secondary to RT suggest
      that the routine use of alpha1-adrenoreceptor antagonists should be considered in
      patients treated with RT, either prophylactically or at the earliest sign of
      LUTS.

PMID- 17023791
TI  - Cutaneous angiosarcoma.
AB  - OBJECTIVE: To discuss the treatment and outcomes for cutaneous angiosarcoma.
      METHODS: Review of the pertinent literature. RESULTS: Cutaneous angiosarcoma is a
      rare, aggressive malignancy with a poor prognosis. It usually arises in the scalp
      or face and is locally advanced at presentation. Patients are most often white,
      male, and elderly. A subset of patients presents with multifocal disease and/or
      positive regional nodes. Although the optimal treatment is surgery followed by
      wide-field radiotherapy (RT), the disease is frequently so extensive at diagnosis
      that it is not completely resectable. Even after optimal local-regional
      treatment, there is a relatively high likelihood of a local recurrence at the
      margins of the RT fields. The probability of hematogenous dissemination is
      relatively high. Limited data suggest that chemotherapy may be useful for
      palliation with progression-free survival rates ranging from 1 to 5 months. The 5
      year local-regional control rates are approximately 40% to 50%, the 5-year
      distant metastasis-free survival rates range from 20% to 40%, and the 5-year
      survival rates range from 10% to 30%. CONCLUSION: Cutaneous angiosarcoma is a
      rare, aggressive malignancy that is optimally treated with resection and wide
      field postoperative RT. The likelihood of local-regional failure is high, as is
      the risk of distant relapse. Chemotherapy may be useful for short-term
      palliation.

PMID- 17023792
TI  - Unusual manifestation of Hodgkin disease.

PMID- 17023793
TI  - Blepharitis induced by epidermal growth factor receptor-targeting therapy.

PMID- 17023794
TI  - Synchronous fibrosarcoma and medullary thyroid cancer in a man with AIDS.

PMID- 17023795
TI  - Acute proctocolitis with commencement of neoadjuvant chemoradiation for rectal
      cancer.

PMID- 17023797
TI  - RSO interview with Jack Topper. Interview with a radiation safety officer.
      Interview by Rene Michel.

PMID- 17023799
TI  - Effect of geotropism on instrument readings. Calibrating survey meters to account
      for geotropism is discussed.
AB  - Geotropism is an analog meter's response due to orientation in a gravitational
      field whether radiation is present or not. For a conventional analog meter, the
      geotropic response is reflected in the movement of the meter needle. Geotropism
      is not relevant for digital portable survey (e.g., liquid crystal displays) or
      stationary bench top meters. The degree of geotropism must be evaluated during
      type testing and routine calibration when dealing with portable survey
      instruments. Geotropism is defined in , , and as a change in instrument reading
      with a change in instrument orientation as a result of gravitational effects.
      Ideally, the manufacturer when selecting a meter movement for a particular
      portable survey instrument application considers geotropism in their selection.
      However, simply employing high quality meters in the manufacture of instruments
      is not sufficient, since survey meters may be damaged to the point that
      geotropism may be exhibited. Awareness of geotropism and the ability to recognize
      its occurrence are invaluable to radiation protection technologists, especially
      those who calibrate or evaluate survey instruments in the course of doing their
      job.

PMID- 17023800
TI  - An investigation of voxel geometries for MCNP-based radiation dose calculations.
AB  - Voxelized geometry such as those obtained from medical images is increasingly
      used in Monte Carlo calculations of absorbed doses. One useful application of
      calculated absorbed dose is the determination of fluence-to-dose conversion
      factors for different organs. However, confusion still exists about how such a
      geometry is defined and how the energy deposition is best computed, especially
      involving a popular code, MCNP5. This study investigated two different types of
      geometries in the MCNP5 code, cell and lattice definitions. A 10 cm x 10 cm x 10
      cm test phantom, which contained an embedded 2 cm x 2 cm x 2 cm target at its
      center, was considered. A planar source emitting parallel photons was also
      considered in the study. The results revealed that MCNP5 does not calculate total
      target volume for multi-voxel geometries. Therefore, tallies which involve total
      target volume must be divided by the user by the total number of voxels to obtain
      a correct dose result. Also, using planar source areas greater than the phantom
      size results in the same fluence-to-dose conversion factor.

PMID- 17023801
TI  - A security vulnerabilities assessment tool for interim storage facilities of low
      level radioactive wastes.
AB  - Limited permanent low-level radioactive waste (LLRW) disposal capacity and
      correspondingly high disposal costs have resulted in the creation of numerous
      interim storage facilities for either decay-in-storage operations or longer term
      accumulation efforts. These facilities, which may be near the site of waste
      generation or in distal locations, often were not originally designed for the
      purpose of LLRW storage, particularly with regard to security. Facility security
      has become particularly important in light of the domestic terrorist acts of
      2001, wherein LLRW, along with many other sources of radioactivity, became
      recognized commodities to those wishing to create disruption through the
      purposeful dissemination of radioactive materials. Since some LLRW materials may
      be in facilities that may exhibit varying degrees of security control
      sophistication, a security vulnerabilities assessment tool grounded in accepted
      criminal justice theory and security practice has been developed. The tool, which
      includes dedicated sections on general security, target hardening,
      criminalization benefits, and the presence of guardians, can be used by those not
      formally schooled in the security profession to assess the level of protection
      afforded to their respective facilities. The tool equips radiation safety
      practitioners with the ability to methodically and systematically assess the
      presence or relative status of various facility security aspects, many of which
      may not be considered by individuals from outside the security profession. For
      example, radiation safety professionals might not ordinarily consider facility
      lighting aspects, which is a staple for the security profession since it is
      widely known that crime disproportionately occurs more frequently at night or in
      poorly lit circumstances. Likewise, the means and associated time dimensions for
      detecting inventory discrepancies may not be commonly considered. The tool
      provides a simple means for radiation safety professionals to assess, and perhaps
      enhance in a reasonable fashion, the security of their interim storage
      operations. Aspects of the assessment tool can also be applied to other
      activities involving the protection of sources of radiation as well.

PMID- 17023802
TI  - Radiation protection at an aviation museum.
AB  - The U.S. Nuclear Regulatory Commission (U.S. NRC) will soon publish a proposed
      amendment to its rules that will classify the naturally occurring isotope Ra as
      "byproduct material" subject to its regulatory control. One of the uses of radium
      in the first half of the twentieth century was as a source of energy that would
      make certain consumer products "glow in the dark." In addition to wristwatches
      and other timepieces, this form of self-luminescence was widely used on aircraft
      instruments. There have been a number of facilities where large numbers of such
      instruments were stored and leakage of this isotope occurred. Subsequent
      decontamination of these areas, including expensive disposal of the radioactive
      waste, was required. We were asked to evaluate the potential hazards of aircraft
      and aircraft instruments at a museum in New York City, specifically the
      decommissioned aircraft carrier USS Intrepid. We present the results of our
      investigation and discuss the implications as they relate to the proposed new
      U.S. NRC regulations and compatibility issues with State regulations.

PMID- 17023803
TI  - Lessons learned in responding to and recovering from a fire incident.
AB  - A review is presented of the response by emergency personnel, including radiation
      safety staff, to a fire incident in an academic radiation facility. The handling
      of the incident during the incident itself as well as during post-fire cleanup
      and recovery efforts are described. The preparation of a variety of written
      notification reports and the physical and procedural corrective actions taken as
      a result of the fire are also discussed.

PMID- 17023804
TI  - Balloon brachytherapy for brain tumor-radiation safety experiences at the
      University of Medicine and Dentistry of New Jersey.
AB  - Balloon brachytherapy is a technique for the removal of a brain tumor in which an
      inflatable balloon is placed in a resection cavity and then filled with liquid I,
      delivering low energy dose to the cancerous cells surrounding the cavity. After
      preparing a patient room to mitigate any spills or contamination, liquid 125I
      (Iotrex) was assayed with a dose calibrator and injected into the balloon placed
      in the patient's brain. Approximately 98.6% of the isotope was recovered at the
      end of the procedure. Approximately 1.4% remained unrecovered and is assumed to
      have diffused through the balloon membrane. Each day, the patient's urine was
      collected and the total urine activity measured was less than 7% of the
      unrecovered activity. The remainder of the unrecovered activity was not
      evaluated. It was assumed to be distributed in the patient's body, and a tiny
      quantity of liquid spilled from an IV line while injecting. Training was
      conducted for radiation oncologists, neurosurgeons, and participating residents
      regarding balloon brachytherapy radiation safety precautions. Precautions during
      treatment included safe handling of body fluids. General radiation safety
      precautions and nursing care instructions were posted on the patient door. Air
      monitoring was conducted to detect any airborne iodine. At the time of balloon
      removal, the radiation safety department monitored the operating room and staff
      for contamination. Waste, including the balloon, was held for decay on site prior
      to disposal.

PMID- 17023805
TI  - Resolution of radio frequency exposure concerns at Woods Hole Oceanographic
      Institution with a collaborative approach.
AB  - Numerous employees at the Woods Hole Oceanographic Institution (WHOI) have
      expressed health concerns about occupational exposures to various radio frequency
      radiation (RFR) sources. These RFR sources of concern include primarily radar
      systems (ship and experimental) and various communication systems (ship, roof top
      transmitting and receiving antennas, and portable transceivers). A certified
      testing service and an independent health physics consultant evaluated the RFR
      exposures using appropriate methods and concluded that all occupied work areas
      were below the applicable maximum permissible exposure (MPE) limits. Despite
      these independent conclusions, numerous employees continued to express health
      concerns and an interest in evaluating their exposures with a monitoring device
      that was more representative of their personal exposure (i.e., could be worn on
      body). To facilitate resolution of these concerns, a collaborative approach
      between the Environmental, Health & Safety Office and the concerned employees was
      developed that included: 1) a literature search was conducted and information on
      RFR health effects, exposure limits, and assessment methods was compiled and made
      available to all concerned employees; 2) all RFR sources of concern were
      identified and characterized by frequency; 3) an RFR personal monitor was
      evaluated and selected; 4) RFR exposures were evaluated with full-shift
      monitoring; and 5) data logged monitoring results and the relevant exposure
      limits were evaluated. All monitored exposures have been less than 10% of the MPE
      limit from the Institute of Electrical and Electronics Engineers (IEEE) Standard
      C95.1-1999 for controlled areas, and all occupational RFR exposure concerns have
      been resolved.

PMID- 17023806
TI  - Asymptomatic sensorineural hearing loss in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Hearing loss can accompany systemic lupus erythematosus (SLE). The
      purpose of this study was to evaluate the prevalence of asymptomatic
      sensorineural hearing loss (ASNHL) in patients with SLE. METHODS: Thirty-one
      unselected consecutive female patients with SLE (American College of Rheumatology
      criteria, 1982) were evaluated (in a prospective and descriptive study) for
      evidence of hearing abnormalities. Twenty-five healthy age-matched women served
      as controls. All patients and control groups underwent both a normal tympanoscopy
      and an audiometric testing as a prerequisite to be included in the study.
      RESULTS: Patients with SLE had a mean age of 35 years (range, 19-64 years) and
      the follow-up time (median) was 48 months (range, 4-180 months). One of 31
      patients was excluded because of middle ear infectious disease. Of the remaining
      30 patients, 21 (70%) had impaired hearing; 20 (66%) had sensorineural loss at
      high frequencies in a bilateral and symmetric way, and one had conductive
      alteration. Ten patients had normal audiometric studies. Four women in the
      control group had alterations of the audiometric tests: 3 patients had conductive
      alteration and the other one had bilateral ASNHL. No statistically significant
      correlation was found among the presence of ASNHL, the detection of
      antiphospholipid antibodies, and the treatment with hydroxychloroquine. Also, no
      correlation was observed between impaired hearing and SLE activity. CONCLUSION:
      If it can be established how often this ASNHL progresses to a clinical problem,
      it can be important that, as part of initial studies, patients with SLE undergo
      audiometric tests.

PMID- 17023807
TI  - Prevalence of evaluation and treatment of glucocorticoid-induced osteoporosis in
      men.
AB  - BACKGROUND: Screening and treatment of glucocorticoid- induced osteoporosis in
      male patients is less than recommended despite available screening and therapies.
      OBJECTIVES: We determined if men treated with long-term oral glucocorticoid
      therapy for any reason receive assessment and therapy for the prevention and
      treatment of glucocorticoid-induced osteoporosis. METHODS: A retrospective
      computer-generated chart review was performed involving all men given prednisone
      from January 2002 through July 2002. There were 370 patients evaluated from the
      James A. Haley Veterans Affairs Hospital, Tampa, Florida, a large teaching
      hospital for the University of South Florida College of Medicine. Charts were
      reviewed for bone mineral density testing; dose, duration, and indication of
      glucocorticoid therapy; age of the patients as of January 2002;continuous or
      intermittent dosing; history of fracture; bone loss prevention medication use,
      including bisphosphonate, calcitonin, testosterone replacement therapy, calcium,
      and vitamin D; and the steroid-prescribing and screening practitioner's specialty
      and sex. RESULTS: Of the 370 men, 258 used 7.5 mg prednisone or more daily and
      295 used glucocorticoids for more than 3 months. Of the 370 men, 163 had a bone
      mineral density test; 87 were treated with a bisphosphonate. Calcium and vitamin
      D were given to half of the patients. Of the patients with a normal T-score, 13
      of 55 were treated with a bisphosphonate (24%) compared with 24 of 40 (60%) with
      an osteopenic score and 14 of 21 (67%) with osteoporosis. Of the 46 patients with
      no score available but indication that it had been ordered or otherwise
      addressed, 23 patients were treated empirically with a bisphosphonate.
      Rheumatology screened 75% of their patients, whereas primary care screened 30% of
      their patients. CONCLUSIONS: Bone mineral density testing was performed or
      ordered for less than half of the glucocorticoid-treated patients and less than
      one third were taking bisphosphonate therapy. Further intervention is needed to
      increase prevention of glucocorticoid-induced osteoporosis and subsequent risk of
      fracture.

PMID- 17023808
TI  - Low frequency of anticyclic citrullinated peptide antibodies in psoriatic
      arthritis but not in cutaneous psoriasis.
AB  - BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) antibodies are highly
      specific for the diagnosis of rheumatoid arthritis (RA). The clinical distinction
      between RA and psoriatic arthritis (PsA) is often difficult to establish;
      therefore, the presence of rheumatoid factor (RF) and anti-CCP antibodies could
      be useful. Seven percent to 40% of patients with longstanding psoriasis will
      develop PsA at some point. Therefore, it is important to study the positivity of
      these antibodies in these two interrelated populations. OBJECTIVE: The aim of
      this study was to determine the seropositivity of anti-CCP antibodies in patients
      with psoriasis and PsA and to compare it with that seen in patients with other
      inflammatory, noninflammatory (osteoarthritis) arthritides and healthy controls.
      PATIENTS AND METHODS: Serum anti-CCP antibodies were measured in 106 patients
      with cutaneous psoriasis, 72 patients with PsA, 41 healthy controls (HC), 41
      patients with undifferentiated or early inflammatory arthritis (UA), and 41
      patients with RA and 41 with osteoarthritis using a commercial second-generation
      enzyme-linked immunosorbent assay. We considered a positive result to be >20
      UI/mL, as recommended by the manufacturer. RESULTS: Of 106 patients with PsA, 55
      were women and 51 men. The mean age was 42.87 +/- 17.71 years and the mean
      disease duration was 5.3 +/- 2.10 years. Anti-CCP antibodies were not present in
      patients with psoriasis without arthritis. In contrast, 7 of 72 (9.72%) patients
      with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units.
      Only one patient with PsA was positive for RF. Most of these patients were female
      with polyarticular joint involvement. Distal interphalangeal involvement was
      present in 4 and 2 had dactylitis. We found clear differences when we compared
      patients with PsA with patients with psoriasis (P = 0.001). Of the 43 patients
      with UA studies, 4 initially exhibited a low titer positive anti-CCP antibody,
      and at follow up, another patient developed anti-CCP antibodies and later
      developed RA. None of the patients with UA developed PsA at 5-year follow up.
      Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean +/-
      standard deviation of the anti-CCP units was 80.61 +/- 55.5.2. Six of the 41
      (14.6%) patients with osteoarthritis studied had positive anti-CCP with a mean
      titer of 7.388. None of the healthy controls exhibited positively for anti-CCP
      antibodies. CONCLUSION: Anti-CCP antibodies may be found in patients with PsA and
      not in our patients with only cutaneous psoriasis. These antibodies may also be
      found in some patients with osteoarthritis and rarely in patients with UA; such
      patients will be of interest to follow prospectively.

PMID- 17023809
TI  - What is that nodule? A diagnostic approach to evaluating subcutaneous and
      cutaneous nodules.
AB  - The evaluation of patients with subcutaneous nodules remains a diagnostic
      challenge. The presence of nodules can be a clue to an underlying systemic
      disease; however, the varied presentations of nodules and numerous disease
      associations make the assessment of patients with nodules far from simple. With
      further investigation into the appearance, location, and symptoms associated with
      nodules, the clinical significance of these lesions can become clearer and aid in
      logical diagnostic evaluation. We have reviewed the causes of nodules with
      emphasis on those associated with rheumatic disease and provide guidelines for
      nodule evaluation to better characterize disease association and lead to directed
      diagnostic assessment.

PMID- 17023810
TI  - Interferon-induced sarcoidosis.
AB  - Rheumatologists are increasingly asked to see patients with hepatitis C who
      exhibit a variety of clinical and serologic features that mimic systemic
      rheumatic disease. Treatment with interferons, now the standard of care, can
      precipitate a variety of inflammatory conditions, including sarcoidosis. We
      present a case of a 59-year-old former intravenous drug user who developed
      systemic sarcoidosis while receiving interferon alpha and ribavirin for the
      treatment of chronic hepatitis C. Because interferons are increasingly prescribed
      by specialists in a variety of disciplines, rheumatologists should be aware of
      their potential to induce sarcoidosis as well as various autoimmune diseases.

PMID- 17023811
TI  - Henoch-Schonlein purpura after etanercept therapy for psoriasis.
AB  - Etanercept is a recombinant dimeric fusion protein consisting of a tumor necrosis
      factor-alpha receptor ligand-binding region linked to the Fc portion of human
      IgG. It is approved for use in the treatment of rheumatoid arthritis, ankylosing
      spondylitis, juvenile rheumatoid arthritis, psoriasis, and psoriatic arthritis.
      Since 1998, there have been reports of vasculitic adverse events, including
      necrotizing vasculitis and leukocytoclastic vasculitis. In addition, the adverse
      events reporting system of the U.S. Food and Drug Administration has recorded 35
      cases of leukocytoclastic vasculitis, 20 after etanercept therapy and 15 after
      infliximab. Most cases of cutaneous vasculitis describe development of symptoms
      within 3 months of etanercept use. In only one case report was direct
      immunofluorescence performed on tissue and no specific immunoreactivity found. We
      describe the first case of Henoch-Schonlein purpura with acute renal failure
      associated with increase in etanercept dose after 11 months of use for treatment
      of psoriasis. Discontinuation of the drug and treatment with a course of systemic
      steroids led to the complete resolution of the vasculitis and improvement of
      renal function. Vasculitis occurring even during chronic use of antitumor
      necrosis factor agents must be considered as possibly related to the therapy.

PMID- 17023812
TI  - Multicentric reticulohistiocytosis presenting with destructive polyarthritis,
      laryngopharyngeal dysfunction, and a huge reticulohistiocytoma.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare multisystemic disease
      presenting with skin lesions and erosive polyarthritis and is often associated
      with malignancy. We describe a 60-year-old woman with diffuse papulonodular skin
      eruptions and progressive osteolytic bone damage over the bilateral hands,
      humeral head, and acromioclavicular joints within 2 years. Moreover, dysphagia
      and a hoarse voice occurred in this patient and an unusual huge mass
      reticulohistiocytoma--developed over the left upper back. Tissue biopsy of the
      skin lesions, laryngeal nodules, and this large mass showed infiltration of
      numerous CD68(+) histiocytes and multinucleated giant cells with abundant
      eosinophilic ground-glass cytoplasm. Combination therapy with steroids and
      methotrexate improved her cutaneous, joint, and laryngopharyngeal symptoms. The
      large reticulohistiocytoma resolved with methylprednisolone pulse therapy. This
      polyarthritis, which can be confused with rheumatoid arthritis, can be diagnosed
      by careful immunohistochemical examination of biopsies. To prevent the
      irreversible disease process, early and aggressive therapy is necessary.

PMID- 17023813
TI  - Basic science for the clinician 40: ubiquitin, programmed protein degradation,
      and the proteasome.
AB  - mRNA is made from DNA. Protein is made from mRNA. Although one might say that
      "DNA is forever," the same cannot be said for mRNA or protein. These molecules
      are made in response to the cell's present needs; once the cell's circumstances
      change, a whole new repertoire of proteins may be needed and the previous set of
      proteins may be unnecessary, perhaps even deleterious. So, the cell must be able
      to eliminate the characters in the previous act in favor of the actors needed for
      the current act. In addition, there is good evidence that the DNA to mRNA to
      protein flow may not be efficient; abnormal proteins, as well as damaged or
      misfolded proteins, are quite common and must also be eliminated. This process
      depends on the ability of the cell to tag the protein to be eliminated with a
      small protein (or chain of these proteins) that targets the protein to a special
      structure for digestion into its constituent amino acids for recycling into new
      proteins. This very common protein tag was identified in the 1970s and called
      "ubiquitin"--it truly was everyplace! In addition, ubiquitin is crucial to
      targeting normal proteins to their appropriate place in or on the cell and for
      recycling of proteins. Ubiqutination of proteins and what follows this tagging
      are crucial to the normal function of cells. The complexity of these processes is
      being used for therapy in oncology now and perhaps in immunology and rheumatology
      in the near future.

PMID- 17023814
TI  - Limited Wegener's granulomatosis manifested by abducens nerve palsy resulting
      from pachymeningitis.

PMID- 17023815
TI  - Systemic lupus erythematosus after mesotherapy with acetyl-L-carnitine.

PMID- 17023816
TI  - The appearance of pustular psoriasis during antitumor necrosis factor therapy.

PMID- 17023817
TI  - Systemic lupus erythematosus associated with acute cytomegalovirus infection.

PMID- 17023818
TI  - A case of Wegener's granulomatosis complicated with hydropneumothorax.

PMID- 17023819
TI  - Histologic signs of inflammatory myopathy in familial Mediterranean fever.

PMID- 17023820
TI  - Rheumatoid neutrophilic dermatitis.

PMID- 17023821
TI  - A letter from a rheumatology colleague in Baghdad.

PMID- 17023822
TI  - Pilot study to evaluate MYCN expression as a neuroblastoma cell marker to detect
      minimal residual disease by RT-PCR.
AB  - This pilot study was performed to determine whether MYCN expression warrants
      further investigation as a tumor marker to detect low levels of residual
      neuroblastoma (NB). Seven NB cell lines and 30 bone marrow (BM) samples from
      patients with high-risk NB were analyzed by reverse transcriptase-polymerase
      chain reaction (RT-PCR) for MYCN expression, and for the established NB marker
      tyrosine hydroxylase. MYCN was expressed in all 7 NB cell lines, but not in
      normal peripheral blood, CD34 cells, or BM. In dilution studies using cell lines
      with or without DNA amplification of MYCN, 1 NB cell in 10 to 10 nucleated blood
      cells was detectable by RT-PCR. MYCN was identified in all 21 BM samples in which
      tumor cells were identified by histologic examination, including 4 samples in
      which tyrosine hydroxylase was not detected. Additionally, expression of both
      markers was detected in 5 samples that were negative by histology but presumably
      contained low levels of tumor cells, consistent with the greater sensitivity of
      RT-PCR compared with morphologic methods. Detection of MYCN RNA was independent
      of MYCN DNA amplification status. The selective expression of MYCN in tumor
      cells, and the sensitivity of detection of MYCN by RT-PCR noted in this and other
      studies, supports further evaluation of MYCN as a NB marker for molecular
      detection of minimal residual disease.

PMID- 17023823
TI  - Retinoblastoma in New South Wales 1975 to 2001.
AB  - PURPOSE: To examine the epidemiology of retinoblastoma in New South Wales (NSW),
      from 1975 to 2001, comparing the incidence with other parts of the developed
      world. METHODS: Examination of medical files for patients presenting to NSW
      retinoblastoma treatment centers between 1975 and 2001. Comparisons to
      international data were made. RESULTS: One hundred twenty-eight patients [63
      (49.2%) male and 65 (51.8%) female] presented. The mean annual incidence of
      retinoblastoma in NSW was 8 per million children aged 0 to 6 years, per year.
      CONCLUSIONS: The incidence of retinoblastoma in NSW is similar to other parts of
      the developed world.

PMID- 17023824
TI  - Stiffness of the abdominal aorta in beta-thalassemia major patients related with
      body iron load.
AB  - OBJECTIVES: Increased iron stores have been implicated in the association with
      increased risk of cardiovascular events. We evaluated whether the abdominal
      aortic stiffness was altered in the patients with beta-thalassemia major in
      relation with body iron load. METHODS: Sixty-two (32 males and 30 females) beta
      thalassemia major patients aged 16.47 +/- 4.8 years were enrolled into the study.
      Healthy 52 subjects matched for age and sex were recruited as controls. In all
      subjects, hemoglobin, fasting glucose, cholesterol, high-density lipoprotein
      cholesterol, and low-density lipoprotein-cholesterol levels were measured. The
      average serum ferritin level and liver iron concentration (LIC) were assessed in
      thalassemia patients. Left ventricular function and mass were evaluated
      echocardiographically and aortic strain (S), pressure strain elastic modulus
      (Ep), and normalized Ep (Ep*), aortic distensibility (DIS), and beta stiffness
      index (beta index) were calculated in all subjects. RESULTS: There was no
      statistically significant difference between the study and control groups in sex,
      mean age, body mass index, heart rate, and systolic blood pressure (P > 0.05).
      However, pulse pressure and left ventricular mass index (LVMI) were found higher
      in thalassemia major patients compared with the control group. In beta
      thalassemia major patients S (0.21 +/- 0.027 vs. 0.26 +/- 0.017, P < 0.0001) and
      DIS (1.07 +/- 0.25 vs. 1.56 +/- 0.37, P < 0.0001) were significantly lower
      compared with the control group. However, Ep (196.9 +/- 44.86 vs. 134.20 +/-
      29.10, P < 0.0001), Ep* (3.26 +/- 0.98 vs. 2.04 +/- 0.60, P < 0.0001), and beta
      index (2.44 +/- 0.58 vs. 1.61 +/- 0.37, P < 0.0001) were significantly higher in
      beta-thalassemia patients than controls. There was a statistically significant
      negative correlation between LIC and S, DIS. There was also negative correlation
      between LVMI and S. However, there was a statistically significant positive
      correlation between LIC and Ep, Ep*. CONCLUSIONS: Increased abdominal aortic
      stiffness was detected in beta-thalassemia major patients and this increase in
      arterial stiffness correlated with LIC and LVMI.

PMID- 17023825
TI  - Use of rFVIIa in 4 children with Glanzmann thrombasthenia.
AB  - Inherited deficiencies of platelet surface glycoproteins, such as Glanzmann
      thrombasthenia (GT), occasionally result in severe bleeding episodes. Platelet
      transfusion is considered standard therapy for securing hemostasis in subjects
      with GT when local measures and antifibrinolytic agents are inadequate. We
      describe 4 case studies which suggest that recombinant activated factor VII may
      be an effective alternative to platelet transfusion in preventing or controlling
      bleeding, including surgical bleeding, in patients with GT.

PMID- 17023826
TI  - Hypertension in childhood cancer: a frequent complication of certain tumor sites.
AB  - The clinical features and management of severe hypertension (HT) (blood pressure
      > 99th percentile + 5 mm Hg) have been rarely described in pediatric oncology.
      OBJECTIVES: Retrospective descriptive study of the case files of 31 patients
      followed in the Institut Curie Department of Pediatric Oncology between 1999 and
      2004 and presenting severe HT at the time of diagnosis of their tumor. RESULTS:
      The median age was 2 years 1 month (range: 3 mo to 6 y 8 mo). Median blood
      pressure was 99th percentile + 30 mm Hg (range: 99th percentile + 7 mm Hg to 99th
      percentile + 62 mm Hg). The tumors presented by these children were: Wilms tumor
      (n=17, ie, 20% of all Wilms tumors treated during this period), neuroblastoma
      (n=12, ie, 10% of all neuroblastomas treated during this period) or other tumors
      (n=2). HT was asymptomatic in all children. Initial management consisted of
      etiologic treatment by primary chemotherapy and/or surgical resection of the
      tumor, associated with antihypertensive therapy, initially administered by
      intravenous injection for 12 children (nicardipine, labetalol) and then orally in
      all children (calcium channel blockers, n=23; angiotensin-converting enzyme
      inhibitor, n=16; beta-blockers, n=4; alpha/beta-blockers, n=2; diuretics, n=1).
      Dual therapy was necessary in 7 cases and triple therapy was necessary in 1 case.
      The median duration of antihypertensive therapy was 40 days (range: 9 to 195). No
      child developed a serious complication of HT. CONCLUSIONS: Initial HT is a
      frequent complication of Wilms tumor and neuroblastoma and affects young children
      (< 2.5 y). It is often severe, asymptomatic, but needs specific treatment and
      resolves after treatment of the tumor.

PMID- 17023827
TI  - A proposed score for predicting severe infection complications in children with
      chemotherapy-induced febrile neutropenia.
AB  - BACKGROUND: Febrile neutropenia (FN) is one of most common complications in
      patients with cancer during chemotherapy. Identifying factors associated with
      severe infectious complications (SICs) at time of admission for fever and
      neutropenia is necessary for better treatment. PROCEDURE: We revised all medical
      charts of patients under 18 years old who developed a first episode of FN present
      from January 2000 to December 2003. Criteria for a SIC were defined. These
      included the presence of bacteremia or fungemia, sepsis, septic shock, and/or
      death from infection. To identify risk factors SIC was associated with the first
      FN episode. RESULTS: Factors identified in univariate analysis were female sex,
      age less than 5 years old, acute myeloid leukemia, baseline disease activity, use
      of central venous catheter, hemoglobin level < 7 g/dL, leukocytes count < 500
      cells/mm(3), granulocytes count < 500 cells/mm(3), monocytes count < 100
      cells/mm(3), platelets < 20,000, and body temperature > 38.5 degrees C, a
      chemotherapy interval < 7 days, presence of mucositis, pneumonia, absence of
      upper respiratory tract infection, or the presence of any clinical focus on first
      physical examination. In multivariate analysis the variables that remained as
      independent predictive risk factors for SIC were age less than 5 years, use of
      central venous catheter, body temperature > 38.5 degrees C, hemoglobin level < 7
      g/dL, any clinical focus of infection on first examination and absence of upper
      respiratory tract infection. The FN population was than divided among 3 different
      risk groups as follows: group 1 (low risk), group 2 (intermediate risk), with a
      13 (4.4 to 38.3)-fold risk for SIC; and group 3 (high risk) with a 50 (16.4 to
      149.2)-fold risk for SIC. CONCLUSIONS: This study suggests that patients with FN
      can be stratified for risk of SIC using clinical parameters at hospital
      admission.

PMID- 17023828
TI  - Effects of acute exercise on neutrophils in pediatric acute lymphoblastic
      leukemia survivors: a pilot study.
AB  - PURPOSE: This nonrandomized controlled trial was designed to investigate the
      effects of acute exercise on neutrophil count and function in children and
      adolescents receiving maintenance treatment for acute lymphoblastic leukemia
      (ALL) compared to matched controls. METHODS: Participants (n = 10; 4 ALL patients
      and 6 healthy matched controls) were males between the ages of 7 to 18 years. On
      visit 1, participants completed an incremental exercise test to volitional
      exhaustion on a treadmill to determine peak aerobic fitness (VO(2peak)). On visit
      2, participants completed a 30-minute exercise session consisting of an
      intermittent run-walk on a treadmill at 70% to 85% of VO(2) peak with blood
      sampling completed at 5 time points: fasting, preexercise, postexercise, 1-hour
      postexercise, and 2-hour postexercise. RESULTS: A significant increase in
      absolute neutrophil count from preexercise to postexercise was observed in both
      groups (P = 0.011). Neutrophil oxidative capacity was significantly depressed in
      the ALL group at the basal level (P = 0.029), however, it increased in both
      groups after exercise and stimulation. CONCLUSIONS: This preliminary study
      suggests that 30 minutes of moderate intensity exercise in ALL patients receiving
      maintenance therapy provides a similar neutrophil response to that of healthy age
      and sex-matched controls.

PMID- 17023829
TI  - Disseminated nontuberculous mycobacterial infections in sickle cell anemia
      patients.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous in nature and have been
      implicated in skin/soft-tissue, pulmonary, middle ear, bone, and
      surgical/traumatic wound infections. Disseminated disease occurs infrequently and
      almost exclusively in the immunocompromised. We describe the first 2 reported
      cases of disseminated Mycobacterium fortuitum infection in teenagers with sickle
      hemoglobinopathy. Both had central venous catheters (CVCs), frequent admissions
      for vaso-occlusive painful episode and received hydroxyurea. Diagnosis was
      confirmed by multiple positive blood cultures and pulmonary dissemination
      occurred in both. Both had successful treatment after CVC removal and combination
      drug therapy. Positive cultures persisted in 1 patient due to drug resistance
      emphasizing the need for accurate susceptibility data. NTM infection should be
      added to the list of pathogens in sickle cell patients with CVCs and fever.
      Investigation for disseminated disease should be undertaken based on clinical
      signs and symptoms. Although some routine blood culture systems can identify NTM,
      specific mycobacterial blood culture is optimal. Removal of involved CVCs is
      essential and treatment of NTM must be guided by susceptibilities. As
      dissemination almost always occurs in those with impaired cellular immunity,
      human immunodeficiency virus testing should be performed. Hydroxyurea may be a
      risk factor for dissemination and needs further evaluation.

PMID- 17023830
TI  - A case of Turner syndrome associated with acute myeloid leukemia (M2).
AB  - A 9-year-old girl was diagnosed as acute myeloid leukemia-M2 according to the
      French-American-British classification. In addition, a diagnosis of Turner
      syndrome (TS) was made, on the basis of the presence of the chromosomal
      abnormality, ovarian failure, and abnormal physical features. In particular,
      children with Down syndrome have increased risk of developing acute myeloblastic
      leukemia especially M7. On the other hand, cases of myeloid leukemia that are
      complicated with TS are extremely rare. This is the first report of TS with acute
      myeloid leukemia of M2 subtype and t (8; 21) in children.

PMID- 17023831
TI  - Orbital metastasis in patients with rhabdomyosarcoma: case series and review of
      the literature.
AB  - We present 3 cases of children who developed recurrent rhabdomyosarcoma with
      metastases to the orbit and review the medical literature. Eight additional cases
      have previously been reported. Alveolar rhabdomyosarcoma was diagnosed in 7
      cases. All 11 patients had stage 3 or 4 tumors at diagnosis, but none had orbital
      involvement initially. The mechanism of orbital recurrence is hematogenous in
      nature. Ten of the patients died; 7 of them succumbed with progressive disease
      within 6 months of the orbital recurrence.

PMID- 17023832
TI  - Teratoma in an adolescent with malignant transformation into embryonal
      rhabdomyosarcoma: case report.
AB  - BACKGROUND: The somatic type tumors are occasionally found in nonseminomatous
      germ cell tumors in men. These malignancies are presumed to arise from malignant
      transformation (MT) of teratoma or by differentiation of totipotential germ cell.
      OBSERVATION: A case of MT of germ cell tumor in 17-year-old male into embryonal
      rhabdomyosarcoma is described. The histopathologic diagnosis was that of
      embryonal rhabdomyosarcoma in which no germ cell elements were found. The germ
      cell origin of transformed histology is supported by cytogenetic analysis
      (isochromosome 12p), and elevated alpha(1)-fetoprotein. Despite intensive therapy
      the patient died. CONCLUSIONS: MT of teratoma is rare entity with poor prognosis.

PMID- 17023833
TI  - Antitumor activity of nifurtimox observed in a patient with neuroblastoma.
AB  - BACKGROUND: Chemotherapy-resistant neuroblastoma is a difficult disease to treat
      with poor survival. OBSERVATIONS: We treated a patient with neuroblastoma who had
      progressed on conventional chemotherapy. This 5-year-old girl with chemotherapy
      resistant neuroblastoma developed Chagas disease at the start of salvage
      chemotherapy for which she was also started on nifurtimox. The neuroblastoma
      response to these treatments resulted in clinical remission. In vitro, treatment
      of a neuroblastoma cell line with nifurtimox resulted in decreased cell viability
      whereas no effect was seen on an endothelial cell line. CONCLUSIONS: Nifurtimox
      shows promise as a potential new treatment for neuroblastoma and warrants further
      testing.

PMID- 17023834
TI  - Development of acute megakaryoblastic leukemia from a minor clone in a Down
      syndrome patient with clinically overt transient myeloproliferative disorder.
AB  - A Down syndrome male showed leukocytosis from birth and was diagnosed as
      transient myeloproliferative disorder (TMD). Eight months later, his condition
      had progressed to myelodysplastic syndrome after spontaneous resolution, and it
      then evolved to acute megakaryoblastic leukemia (AMKL) at the age of 20 months.
      Sequencing analysis showed that the predominant TMD and AMKL clones had different
      GATA1 mutations, although a minor TMD clone identical to the AMKL clone was
      present at birth. These observations suggest that a minor clone rather than the
      predominant clone at the time of TMD may give rise to AMKL later on.

PMID- 17023835
TI  - Evaluation of bone metabolism in children with acute lymphoblastic leukemia. A 2
      year study from Northern Greece.

PMID- 17023836
TI  - Inclusion of secondary chronic myelomonocytic leukemia and myeloproliferative
      disease, unclassifiable, in classification of pediatric myeloproliferative
      disorders.

PMID- 17023837
TI  - Treatment-related myelodysplastic syndrome after chemotherapy for childhood low
      grade astrocytoma.

PMID- 17023838
TI  - Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion
      in the rabbit anular-puncture disc degeneration model: effects of depth of
      puncture.
AB  - STUDY DESIGN: In vivo histologic study of nerve ingrowth in the rabbit anular
      puncture disc degeneration model. OBJECTIVE: To examine innervation of
      intervertebral discs and surrounding tissues in the rabbit anular-puncture model
      with various magnitudes of injury. SUMMARY OF BACKGROUND DATA: A rabbit anular
      puncture model of disc degeneration was recently established. However, to our
      knowledge, the neuropathologic changes in the degenerated disc and surrounding
      tissues in this model have not been examined. METHODS: Anular punctures with an
      18-gauge needle at depths of 1 and 5 mm were randomly performed at the L2-L3 or
      L4-L5 discs in New Zealand white rabbits (n = 16; 3.0-3.5 kg). The degree of disc
      degeneration was followed radiographically, and was further evaluated by magnetic
      resonance imaging and histology at sacrifice 4 or 12 weeks after the puncture. To
      identify nerve ingrowth into the discs, the L2-L3 to L4-L5 discs were
      immunostained with an antibody against protein gene product 9.5, a general marker
      for nerve fibers. RESULTS: Significant decreases in disc height and signal
      intensity in magnetic resonance imaging were observed only in the 5 mm punctured
      discs (P < 0.05). In all the discs, including nonpunctured control discs, protein
      gene product 9.5-immunoreactive fibers were only occasionally observed in the
      outermost part of the anulus fibrosus. In the 5 mm punctured discs, nucleus
      pulposus tissues were extruded, and scar tissues formed outside the discs. No
      nerve ingrowth into the needle track lesion at the anular puncture site was
      observed. However, protein gene product 9.5-immunoreactive fibers were observed
      in scar tissues on the surface of the puncture site. This finding was more
      evident in the 5 mm than in the 1 mm punctured discs (P < 0.05). CONCLUSIONS:
      This study indicates that in the rabbit anular-puncture disc degeneration model,
      disc degeneration associated with a higher nerve growth into the scar tissue was
      more evident when induced by a 5 mm than a 1 mm puncture. Although nerve ingrowth
      was observed in the extruded disc tissue, nerve ingrowth into the outer anulus,
      which has been reported in patients with discogenic pain, was not observed during
      the short observation period in this disc degeneration model. The limitation in
      assessing pain by behavior analysis or histologic evaluation of nerve ingrowth
      should be considered. Further studies to identify a surrogate marker of pain
      should be encouraged.

PMID- 17023839
TI  - How many ligations of bilateral segmental arteries cause ischemic spinal cord
      dysfunction? An experimental study using a dog model.
AB  - STUDY DESIGN: Segmental arteries were interrupted bilaterally for up to 7 levels
      to study the effects on spinal cord blood flow and neurologic function in dogs.
      OBJECTIVE: To examine how many ligations of bilateral segmental arteries cause
      ischemic spinal cord dysfunction. SUMMARY OF BACKGROUND DATA: Interruption of
      bilateral segmental arteries for up to 3 levels has been reported not to damage
      spinal cord function. However, to our knowledge, the effects of ligating more
      than 3 levels have not yet been clearly determined. METHODS: There were 15 dogs
      divided into 5 groups: sham group, no ligation; group 1, ligation of bilateral
      segmental arteries at 3 levels (T11-T13); group 2, at 4 levels (T10-T13); group
      3, at 5 levels (T10-L1); and group 4, at 7 levels (T9-L2). Spinal cord blood flow
      at T12 measured by laser Doppler flowmetry, and spinal cord-evoked and motor
      evoked potentials were measured simultaneously until 10 hours after ligation.
      Neurologic function was assessed using a modified Tarlov grading system 1 week
      after operation in 20 other dogs divided into 4 groups (1, 2, 3, and 4). RESULTS:
      Spinal cord blood flow was 99.3%, 80.7%, 71.5%, 44.3%, and 25.0% in the sham
      group, and groups 1, 2, 3, and 4, respectively, 10 hours after ligation. Abnormal
      spinal cord-evoked potentials were observed in 2 of 3 dogs in group 3 and all 3
      in group 4. Abnormal motor-evoked potentials were observed in 1 of 3 dogs in
      group 3 and all 3 in group 4. Postoperative neurologic evaluation identified all
      5 dogs in groups 1 and 2, respectively, and 3 in group 3 as having grade 5. There
      were 2 dogs in group 3 and 3 in group 4 that had grade 4, and 2 in group 4 had
      grade 3. CONCLUSION: Interruption of bilateral segmental arteries at > or =5
      consecutive levels risks producing a spinal cord ischemia capable of injuring the
      spinal cord.

PMID- 17023840
TI  - Adjacent level load transfer following vertebral augmentation in the cadaveric
      spine.
AB  - STUDY DESIGN: In vitro biomechanics. OBJECTIVE: To determine if osteoporotic
      vertebral compression fracture (VCF) augmentation increases adjacent level load
      transfer. SUMMARY OF BACKGROUND DATA: Osteoporotic VCF subsequent to augmentation
      may result from disease progression or increased adjacent level load transfer, or
      both. METHODS: There were 11 T3-T7 and 10 T8-T12 divided by lumbar bone mineral
      density into a normal group (No. 1; n = 11) and an osteoporotic group (No. 2; n =
      10). Strain and centrum stress were measured on T4 and T6 (T3-T7), and T9 and T11
      (T8-T12) during tests in the intact state, following a centrum defect, during and
      after an augmented VCF at T5 or T10, and during a subsequent VCF. Stiffness and
      strength were compared: between groups 1 and 2; among intact, defect, and
      augmented VCF states; and between the initial and subsequent VCF. RESULTS: Group
      1 was stiffer than 2 in compression (P = 0.01) and flexion (P = 0.07), with no
      difference in adjacent level load transfer (strain P = 0.72, centrum stress P =
      0.36) or strength (P = 0.07). The centrum defect reduced compressive stiffness
      from the intact (P = 0.001), which was partially restored following VCF
      augmentation (P = 0.006). There were no differences in flexion stiffness (P > or
      = 0.14). Adjacent level load transfer in flexion exceeded that in compression
      (strain P = 0.001, centrum stress P = 0.19). Initial and subsequent VCF occurred
      at similar forces (P = 0.26) with higher adjacent level load at subsequent
      (strain and centrum stress P = 0.04). CONCLUSIONS: Augmentation of multilevel
      spinal segments with VCF produced by combined compression, flexion, and a centrum
      defect normalizes adjacent level load transfer at physiologic loads. In both
      normal and osteoporotic spinal segments, as loads approach those of the initial
      VCF, protection from augmentation is lost, and subsequent adjacent level VCFs
      occur from extreme loading, and not the augmentation process.

PMID- 17023841
TI  - Classification of congenitally fused cervical patterns in Klippel-Feil patients:
      epidemiology and role in the development of cervical spine-related symptoms.
AB  - STUDY DESIGN: A retrospective cohort and series review. OBJECTIVES: To determine
      the role of cervical spine fusion patterns on the development of cervical spine
      related symptoms (CSS) in patients with Klippel-Feil syndrome (KFS) and evaluate
      age- and time-dependent factors that may contribute to fused cervical patterns
      and the development of the CSS. SUMMARY OF BACKGROUND DATA: Although the
      "hallmark" of KFS is the presence of congenitally fused cervical vertebrae, the
      epidemiology and role of specific cervical fused patterns are limited. In
      addition, the incidence of symptoms and various age- and time-dependent factors
      that are directly attributed to the congenitally fused cervical segments in KFS
      patients is unknown. METHODS: A radiographic and clinical review of 28 KFS
      patients at a single institution. Radiographically, Type I patients were defined
      as having a single congenitally fused cervical segment. Type II patients
      demonstrated multiple noncontiguous, congenitally fused segments, and Type III
      patients had multiple contiguous, congenitally fused cervical segments. Clinical
      records were reviewed for patient demographics, presence and type of symptoms,
      and clinical course. RESULTS: Twelve males and 16 females were reviewed for
      clinical follow-up (mean, 8.5 years) and radiographic assessment (mean, 8.0
      years). The mean age at presentation was 7.1 years; mean age of onset of CSS was
      11.9 years. Clinically, 64% had no complaints referable to their cervical spine.
      Radiographically, 25%, 50%, and 25% were Type I, Type II, and Type III,
      respectively. At final clinical follow-up, 2 patients were myelopathic (Type II
      and Type III) and 2 were radiculopathic (Type II and Type III). Type III patients
      were largely asymptomatic but were associated with the highest risk in developing
      radiculopathy or myelopathy than Type I or Type II patients. Axial symptoms were
      predominantly associated with Type I patients. Myelopathic patients developed
      initial CSS earlier (meanage, 10.6 years) than patients with predominant axial
      (mean age, 13.0 years) or radiculopathic symptoms (mean age, 18.6 years) (P >
      0.05). Patients with radiculopathy or myelopathy were diagnosed at a mean age of
      17.9 years. Type I patients were predominantly females, while males were largely
      Type III. Surgery entailed 11% of patients, composed of 2 myelopathic patients
      (Type II and Type III) and 1 radiculopathic patient (Type II). CONCLUSIONS: In
      our review, 36% of KFS patients had CSS and the majority had axial symptoms.
      Axial neck symptoms were highly associated with Type I patients, whereas
      predominant radicular and myelopathic symptoms occurred in Type II and Type III
      patients. This classification system has promise for early detection for CSS.
      Activity modification should be stressed in KFS patients at high risk for
      neurologic compromise.

PMID- 17023842
TI  - Preliminary report of transpedicle body augmenter vertebroplasty in painful
      vertebral tumors.
AB  - STUDY DESIGN: Transpedicle body augmenter vertebroplasty of painful vertebral
      tumor was retrospectively evaluated. OBJECTIVE: Transpedicle body augmenter
      vertebroplasty was designed to treat spinal tumor with intractable pain
      refractory to conservative management, deformity, biomechanical impairment, and
      neural deficits. SUMMARY OF BACKGROUND DATA: Chemotherapy, hormonal therapy, and
      radiation therapy cannot restore spinal stability. Complication rates of major
      surgery are high. Percutaneous vertebroplasty has a high leakage rate, and tumor
      tissue may be displaced into the canal. Transpedicle body augmenter
      vertebroplasty was designed to treat spinal tumor for pain control and stability.
      METHODS: There were 9 women and 9 men with a mean age of 62.7 +/- 12.6 years
      included. All patients had vertebral pain. Walking was impossible for 12
      patients, and 15 had neurologic deficits. Treatments included manual reduction
      and transpedicle body augmenter vertebroplasty. RESULTS: Mean follow-up time was
      18 months. Mean hospitalization was 7.1 +/- 4.2 days, operating time was 46 +/-
      25 minutes, and blood loss was 263 +/- 157 cc. Neither neurologic deterioration
      nor root irritation was found after transpedicle body augmenter vertebroplasty.
      No dislodgement of the transpedicle body augmenter was found at the final visit.
      According to the visual analog scale, pain was 9.3 before surgery, 3.2 at 2-week
      follow-up, and 2.2 at 3-month follow-up. There were 11 patients (92%) who
      recovered walking ability. Neurologic status improved in 14 patients (93%). The
      satisfaction rate was 89%. CONCLUSION: Transpedicle body augmenter vertebroplasty
      proved to be safe and effective in reducing pain and improving functional status
      of patients with spinal tumor.

PMID- 17023844
TI  - A prospective assessment of SRS-24 scores after endoscopic anterior
      instrumentation for scoliosis.
AB  - STUDY DESIGN: Prospective clinical case series. OBJECTIVE: To evaluate the
      clinical outcome of anterior endoscopic instrumention for scoliosis using the SRS
      24 questionnaire and to examine how these scores change over a 2-year follow-up
      period. SUMMARY OF BACKGROUND DATA: Anterior endoscopic instrumentation
      correction has several advantages compared with open procedures. However, the
      clinical results of this technique using a validated outcome measure have rarely
      been reported in the literature. METHODS: A total of 83 consecutive patients
      underwent endoscopic anterior instrumentation performed at a single unit.
      Patients completed the SRS-24 questionnaire before surgery and at 3, 6, 12, and
      24 months after surgery. The SRS-24 scores were compared between each of the
      follow-up intervals. RESULTS: The pain, general self-image, and function from
      back condition domains improved after surgery (P < 0.05). Activity level
      significantly improved between 3 and 6 months, and both function domains improved
      between 6 and 12 months (P < 0.05). None of the domains increased significantly
      after 1 year. CONCLUSIONS: Endoscopic anterior instrumentation for scoliosis
      significantly improved pain, self-image, and function. The greatest improvement
      in function occurred between 6 and 12 months after surgery. The SRS-24 scores at
      1 year from surgery may provide a good indicator of patient outcome in the long
      term.

PMID- 17023843
TI  - Optimal end-tidal concentration of sevoflurane to test an ankle clonus in
      children.
AB  - STUDY DESIGN: A prospective randomized study on the end-tidal concentrations of
      sevoflurane at which ankle clonus existed. SUMMARY OF BACKGROUND DATA: The ankle
      clonus reflex is a transient neurologic abnormality, which normally occurs in
      patients during emergence from general anesthesia. OBJECTIVE: To determine the
      optimal end-tidal concentration of sevoflurane to test an ankle clonus in
      children during emergence from general anesthesia. METHODS: We studied 30
      children (aged 5-15 years). General anesthesia was induced with thiopental
      sodium. Anesthesia was maintained with sevoflurane, oxygen, and air. At
      completion of surgery, 3% volume of the end-tidal sevoflurane concentration was
      maintained for at least 10 minutes. Ankle clonus was checked at 1.0% to 0.1%
      volume of the end-tidal sevoflurane concentration with an interval of 0.05%
      volume. RESULTS: Of children, 80% had bilateral ankle clonus, which was found
      most frequently when patients responded poorly to verbal commands. The median of
      the end-tidal sevoflurane concentration for a reactive ankle clonus was 0.45%
      volume (interquartile range 0.5% to 0.4% volume). CONCLUSIONS: The ankle clonus
      should be tested at 0.45% volume of end-tidal sevoflurane concentration in
      children undergoing scoliosis surgery during emergence from the general
      anesthesia.

PMID- 17023845
TI  - Rare bilateral C6 spondylolysis and spondylolisthesis in an adolescent athlete:
      evaluation with magnetic resonance imaging and multidetector computerized
      tomography.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To show a rare case of cervical
      spondylolysis and spondylolisthesis secondary to bilateral stress fractures at
      the pedicle laminar junction of C6 in a 16-year-old athlete playing high school
      baseball. SUMMARY OF BACKGROUND DATA: The patient presented with 3 months of neck
      pain and intermittent right arm radicular symptoms. METHODS: Plain radiographs
      and multidetector computerized tomography (CT) of the cervical spines. RESULTS:
      Plain radiographs revealed loss of lower cervical lordosis. Multidetector CT
      indicated bilateral C6 spondylolysis. Magnetic resonance imaging showed bilateral
      marrow edema at the pedicle laminar junction of C6. Treatment included placing
      his neck in a Philadelphia collar for 6 weeks. Follow-up CT revealed progression
      of healing. CONCLUSION: Early diagnosis and appropriate management of these cases
      are important to promote healing.

PMID- 17023847
TI  - Effectiveness of microdiscectomy for lumbar disc herniation: a randomized
      controlled trial with 2 years of follow-up.
AB  - STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To assess
      effectiveness of microdiscectomy in lumbar disc herniation patients with 6 to 12
      weeks of symptoms but no absolute indication for surgery. SUMMARY OF BACKGROUND
      DATA: There is limited evidence in favor of discectomy for prolonged symptoms of
      lumbar disc herniation. However, only one randomized trial has directly compared
      discectomy with conservative treatment. METHODS: Fifty-six patients (age range,
      20-50 years) with a lumbar disc herniation, clinical findings of nerve root
      compression, and radicular pain lasting 6 to 12 weeks were randomized to
      microdiscectomy or conservative management. Fifty patients (89%) were available
      at the 2-year follow-up. Leg pain intensity was the primary outcome measure.
      RESULTS: There were no clinically significant differences between the groups in
      leg or back pain intensity, subjective disability, or health-related quality of
      life over the 2-year follow-up, although discectomy seemed to be associated with
      a more rapid initial recovery. In a subgroup analysis, discectomy was superior to
      conservative treatment when the herniation was at L4-L5. CONCLUSIONS: Lumbar
      microdiscectomy offered only modest short-term benefits in patients with sciatica
      due to disc extrusion or sequester. Spinal level of the herniation may be an
      important factor modifying effectiveness of surgery, but this hypothesis needs
      verification.

PMID- 17023848
TI  - Effect of high-dose intravenous dexamethasone on postlumbar discectomy pain.
AB  - STUDY DESIGN: A prospective, randomized triple-blind clinical trial. OBJECTIVE:
      To evaluate the effect of 40 and 80 mg intravenous (IV) dexamethasone versus
      placebo to reduce postlumbar diskectomy pain. SUMMARY OF BACKGROUND DATA: Lumbar
      discectomy is a procedure to ablate radicular and low pack pain (LBP) in select
      patients. Unfortunately, some patients have radicular pain for several days after
      successful surgery, possibly caused by nerve root inflammation. METHODS: A total
      of 61 patients with single-level herniated lumbar disc at L4-L5 or L5-S1 were
      randomly assigned to 3 groups. After the skin incision, group 1 received 40 mg,
      group 2 received 80 mg IV dexamethasone, and group 3 received placebo. All
      patients also received 50 mg ranitidine IV at the same time. Preoperative and
      postoperative radicular and LBP were evaluated using the visual analog scale.
      Morphine was administered and recorded as a sole pain-killer during hospital
      admission if indicated. Collected data were analyzed using the 1-way analysis of
      variance test. RESULTS: A total of 61 consecutive patients entered the study.
      There were 19 patients who received 40 mg dexamethasone IV (group 1), 20 received
      80 mg (group 2), and 22 received placebo (group 3). Preoperative data, including
      age, sex, level of disc herniation, and radicular and LBP, were statistically
      matched among groups. Postoperative LBP was decreased in all groups equally.
      Based on the visual analog scale, mean radicular pain was significantly decreased
      4.26 points in group 1, 4.15 points in group 2 versus 2.73 points in group 3 (P =
      0.006). Mean total morphine used was also significantly lower in group 1 versus
      group 3 (5.26 vs. 9 mg P = 0.012). CONCLUSION: Intraoperative IV injection of 40
      mg dexamethasone could effectively reduce postoperative radicular leg pain and
      narcotics usage in patients with single-level herniated lumbar disc.

PMID- 17023849
TI  - The degenerated lumbar intervertebral disc is innervated primarily by peptide
      containing sensory nerve fibers in humans.
AB  - STUDY DESIGN: Immunohistochemical study of the sensory innervation of the human
      lumbar intervertebral disc. OBJECTIVE: To determine the type of sensory fibers
      innervating human degenerated lumbar intervertebral discs. SUMMARY OF BACKGROUND
      DATA: Sensory neurons involved in pain perception related to inflammation in rats
      are typically small, peptide-containing neurons immunoreactive for calcitonin
      gene-related peptide (CGRP). Small non-peptide-containing neurons binding to
      isolectin B4 (IB4) may also be involved in pain states, such as nerve injury
      pain. The character of such sensory neurons in humans has not been clarified.
      METHODS: A degenerated, painful lumbar intervertebral disc was harvested from
      each of 8 patients during surgery. Sections were immunostained for protein gene
      product 9.5 (PGP 9.5, a general neuronal marker), CGRP, and IB4. The numbers of
      PGP 9.5- and CGRP-immunoreactive, and IB4-binding nerve fibers in the discs were
      counted. RESULTS: PGP 9.5-immunoreactive fibers were observed in all discs. Nerve
      fibers immunoreactive for CGRP were also observed in 6 of 8 cases. IB4-binding
      nerve fibers were not found in any case. CONCLUSIONS: Almost all of the
      nociceptive nerve fibers in the human intervertebral disc are peptide-containing
      nerve fibers, similar to the rat disc, suggesting that nerve fibers related to
      inflammation may transmit pain originating from human degenerated intervertebral
      discs.

PMID- 17023850
TI  - Small intestinal submucosa as a potential bioscaffold for intervertebral disc
      regeneration.
AB  - STUDY DESIGN: To evaluate the capacity of porcine small intestine submucosa to
      support the in vitro proliferation of human disc cells and the synthesis of
      extracellular matrix that could restore the biochemical properties of the disc.
      OBJECTIVE: To evaluate if porcine small intestine submucosa is a potential
      bioactive scaffold for rescuing degenerative disc cells. SUMMARY OF BACKGROUND
      DATA: Discogenic back pain is associated with alterations of the disc and
      abnormal turnover of the disc extracellular matrix. We hypothesize that a
      biodegradable and biocompatible acellular scaffold such as small intestine
      submucosa, which contains entrapped growth factors, may stimulate disc cells to
      synthesize extracellular matrix, thereby arresting the degeneration, or even
      promoting the regeneration, of the disc. METHODS: Human degenerative anulus and
      nucleus cells were seeded onto small intestine submucosa scaffolds, and evaluated
      over a 3-month period for cell growth (proliferation assay, deoxyribonucleic acid
      content) and matrix composition (glycosaminoglycan and collagen contents).
      RESULTS: As hematoxylin and eosin staining revealed, more than 70% of seeded
      cells attached to the small intestine submucosa surface and invaded throughout
      the scaffold. The macroscopic appearance of cell-seeded scaffolds was
      dramatically modified over time. Cell metabolic activity was confirmed for up to
      3 months. Seeded scaffolds showed a higher glycosaminoglycan content as compared
      to control scaffolds. Toluidine blue staining detected large areas of
      proteoglycans. Positive gene expression for collagens I, II, and X, aggrecan, and
      Sox-9 confirmed deposition of new extracellular matrix components. CONCLUSIONS:
      This pilot study shows that small intestine submucosa is a promising bioactive
      material that could potentially serve as a temporary scaffold for intervertebral
      disc regeneration.

PMID- 17023852
TI  - Preventive effect of erythropoietin on spinal cord cell apoptosis following acute
      traumatic injury in rats.
AB  - STUDY DESIGN: Using a rat spinal cord injury (SCI) model, terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), anti-active
      caspase-3 antibody staining, histological examination, and histochemical studies
      were used to examine the antiapoptotic effect of erythropoietin. OBJECTIVE: To
      evaluate in detail the antiapoptotic effect of erythropoietin following SCI.
      SUMMARY OF BACKGROUND DATA: Although some investigators have reported
      antiapoptotic effects of erythropoietin using the TUNEL method, it has not been
      determined whether erythropoietin can prevent both acute neuronal death and
      secondary injury. Therefore, we examined the temporal and spatial effects of
      erythropoietin using TUNEL and active caspase-3 following SCI. METHODS: An in
      vitro study used a cerebrocortical culture in which the antiapoptotic effect of
      erythropoietin was examined after N-methyl-D-aspartate treatment. Using an in
      vivo study, rats with SCI received erythropoietin intraperitoneally, and were
      examined histologically and immunohistochemically with TUNEL, active caspase-3,
      and cell markers between 6 hours and 7 days after injury. RESULTS:
      Cerebrocortical culture confirmed an antiapoptotic effect of erythropoietin.
      Erythropoietin treatment significantly decreased TUNEL-positive apoptotic neurons
      and oligodendrocytes as early as 6 hours after SCI in rats. This antiapoptotic
      effect was observed until 7 days after injury. In addition, erythropoietin
      treatment significantly decreased the number of active caspase-3 immunoreactive
      cells within the SCI. In the in vitro study, cerebrocortical culture confirmed an
      antiapoptotic effect of erythropoietin. CONCLUSIONS: These findings suggest that
      exogenous erythropoietin decreases the number of apoptotic cells observed between
      the very early and subchronic stages following traumatic SCI.

PMID- 17023853
TI  - Motion compensation associated with single-level cervical fusion: where does the
      lost motion go?
AB  - STUDY DESIGN: Seven adult human cadaveric cervical spines (C2-T1) were
      biomechanically tested in a programmable testing device. OBJECTIVE: Compare the
      effects of incremental single-level fusion at different levels of the cervical
      spine. SUMMARY OF BACKGROUND DATA: Clinical studies have reported degenerative
      symptomatic disc disease at disc levels adjacent to fusion. No known study has
      attempted to delineate the effects of single-level fusion at different levels of
      the cervical spine. METHODS: The spines were tested in flexion, extension, right
      and left lateral bending, and right and left axial rotation for 7 different
      conditions: harvested and 6 independent single-level fused conditions (i.e., C2
      C3, C3-C4, C4-C5, C5-C6, C6-C7, and C7-T1). Segmental motion and global stiffness
      data were normalized to the harvested condition and compared using a 1-way
      analysis of variance followed by a SNK test (P < 0.01). RESULTS: Motion
      compensation was distributed among the unfused segments with significant
      compensation at the segments adjacent to fusion. Significant increases occurred
      at the level above C3-C4 and C4-C5 fusions, and below for C5-C6 and C6-C7 fusions
      in both flexion and extension. CONCLUSIONS: Increase motion compensation occurred
      at segments immediately adjacent to a single-level fusion. Significant
      differences occurred at the level above the fusion site for the C3-C4 and C4-C5
      fusion in both flexion and extension. When the lower levels (C5-C6, C6-C7) were
      fused, a significant amount of increased motion was observed at the levels
      immediately above and below the fusion. However, greater compensation occurred at
      the inferior segments than the superior segments for the lower level fusions (C5
      C6, C6-C7).

PMID- 17023854
TI  - Anterior exposure of the spine for removal of lumbar interbody devices and
      implants.
AB  - STUDY DESIGN: A retrospective review of a consecutive series of 14 patients
      operated on between March 1998 and April 2005. OBJECTIVES: To report on patients
      having undergone revision lumbar surgery anteriorly to remove interbody devices
      placed anteriorly or posteriorly and to determine the incidence of associated
      complications. SUMMARY OF BACKGROUND DATA: The popularity of interbody lumbar
      surgery has grown in recent years. Consequently, the number of anterior revision
      procedures has increased. The risks associated with anterior approach for
      revision procedures and interbody device removal, in particular, have not been
      reported. METHODS: The results of 13 consecutive patients who had removal of
      interbody devices through an anterior approach and 1 patient with removal of
      anterior fixation (7 males, 7 females; mean age 43 years) were reviewed. The
      procedure during which the original implant was placed was a posterior lumbar
      interbody fusion in 4, transforaminal lumbar interbody fusion in 5, and anterior
      lumbar interbody fusion in 5 patients. Four attending spine surgeons performed
      the procedures with the assistance of 4 experienced access surgeons. RESULTS: Ten
      of 14 (71%) patients had complications associated with anterior exposure of
      revision surgery. Vascular injury is the most common complication (57%). Vascular
      complications occurred in 100% (4/4) of the revisions of previous posterior
      lumbar interbody fusions and 80% (4/5) of previous anterior lumbar interbody
      fusions. The complication rate at L4-5 and L5-S1 was 89% and 40%, respectively.
      There was 1 postoperative mortality. CONCLUSIONS: Anterior removal of lumbar
      interbody devices placed anteriorly or posteriorly has a high incidence of
      complication. Average blood loss and hospital stay are increased with revision
      anterior surgery. The vascular complication rate is 2-fold higher at L4-L5 level
      compared to L5-S1.

PMID- 17023855
TI  - Wear and corrosion in retrieved thoracolumbar posterior internal fixation.
AB  - STUDY DESIGN: Posterior thoracolumbar spine implants retrieved as part of routine
      clinical practice over a 2-year period were analyzed to identify wear and
      corrosion. OBJECTIVE: Engineering analyses of retrieved posterior instrumentation
      for indications of performance and failure and correlation of this information
      with clinical factors. SUMMARY OF BACKGROUND DATA: Recent studies have reported
      spinal instrumentation particulate wear debris and have noted the importance of
      design considerations at implant connector interfaces. METHODS: A total of 57
      implants were analyzed from patients (39 female, 18 male) whose average age at
      implantation was 43.9 years (range, 13.7-77.4 years). Time of implantation ranged
      from 2 months to 13.5 years. The top 3 implantation diagnoses were radiculopathy
      (33%), scoliosis (30%), and back pain (25%). Metallurgical analyses were
      performed to characterize the wear and/or corrosion, and fractures of the
      implants. RESULTS: Wear was present in 75%, corrosion in 39%, and fractures in 7%
      of the retrieved implants. Wear and/or corrosion was more prevalent, with respect
      to the total number of implants retrieved, in implants that had been in service
      at least 1 year. There was no evidence of corrosion in any of the Ti implants,
      whereas corrosion was present (with wear) in 58% of the stainless steel (SS)
      implants. Wear and corrosion were more frequently observed in long rods than in
      short rods. Implantation times were longer for SS implants than for Ti implants.
      CONCLUSIONS: Retrieved rods exhibited corrosion, wear, and fracture, with wear
      and corrosion mainly located at the interfaces with hooks, screws, or cross
      connectors. The mechanisms causing this material loss in situ, as well as what
      local or systemic responses it may stimulate are of clinical significance and
      should be studied further.

PMID- 17023856
TI  - A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI)
      and adolescent idiopathic scoliosis: a study of 540 Chinese cases.
AB  - STUDY DESIGN: A genetic association study of estrogen receptor-[alpha] gene
      (ESR1) with adolescent idiopathic scoliosis (AIS) in Chinese. OBJECTIVES: To
      investigate whether: 1) PvuII and XbaI polymorphisms in ESR1 are predisposition
      factor for AIS and 2) these polymorphisms correlate with the severity of
      curvature in AIS. SUMMARY OF BACKGROUND DATA: A common single nucleotide
      polymorphism (SNP) in ESR1 (XbaI) was found to be associated with curve severity
      in Japanese AIS patients recently. The role of ESR1 as a predisposition gene
      using a case-control design in other ethnic groups is required to confirm the
      previous associations. METHODS: A total of 540 Chinese AIS girls with Cobb angle
      above 20 degrees were recruited as cases together with 260 healthy controls. The
      effect of ESR1 SNPs on severity of scoliosis was analyzed in a subgroup of AIS
      patients (n = 364) followed up until skeletal maturity with the maximum Cobb
      angle recorded. Two SNPs in ESR1 were genotyped by PCR-restriction fragment
      length polymorphism in all subjects. RESULTS: The allelic frequency of X allele
      was 23% in both case and control groups. The P allele was found at allelic
      frequency of 40% and 36% in the case and control groups, respectively. No
      association between the two ESR1 SNPs and the occurrence of AIS by both genotype
      and haplotype analysis could be established, suggesting that both SNPs were not
      predisposition alleles for AIS. AIS patients with different genotypes showed no
      difference in the maximum Cobb angle. No association was found between the
      genotype and anthropometric measurements in AIS patients. CONCLUSION: The
      previously reported association with curve severity could not be replicated in
      our large series of Chinese AIS patients. The current study also did not show any
      association of the 2 SNPs with increased risk of having AIS.

PMID- 17023857
TI  - Recovery of pulmonary function following endoscopic anterior scoliosis
      correction: evaluation at 3, 6, 12, and 24 months after surgery.
AB  - STUDY DESIGN: A series of patients with scoliosis undergoing endoscopic anterior
      instrumentation and fusion undertaking repeated pulmonary function assessments.
      OBJECTIVE: To assess recovery of pulmonary function in the 2 years following
      endoscopic anterior scoliosis correction. SUMMARY OF BACKGROUND DATA: Recent
      studies have found that pulmonary function returns to preoperative levels 12-24
      months following endoscopic anterior scoliosis correction, and a small
      improvement in forced expiratory volume (FEV1) has also been reported. METHODS: A
      series of 44 patients with endoscopic anterior scoliosis correction had pulmonary
      function tests before surgery, and at 3, 6, 12, and 24 months after surgery.
      Forced vital capacity (FVC), FEV1, and total lung capacity (TLC) were measured.
      Nonparametric statistical analysis was used to investigate changes in pulmonary
      function between successive assessments. RESULTS: Pulmonary function decreased by
      approximately 10% at 3 months after surgery. At 24 months after surgery, FVC and
      FEV1 recovered to 5% to 8% higher than preoperative levels, while TLC returned to
      preoperative levels. Statistically significant improvements in most pulmonary
      function values occurred between 3 and 6, and 6-12 months. Improvements in mean
      FVC, FEV1, and TLC continue between 12 and 24 months, although only the increase
      in absolute FVC for this time is statistically significant. CONCLUSIONS:
      Endoscopic anterior scoliosis surgery has no lasting negative effect on pulmonary
      function, and with prolonged follow-up, pulmonary capacity improves beyond
      preoperative levels.

PMID- 17023858
TI  - Correction of neuromuscular scoliosis in patients with preexisting respiratory
      failure.
AB  - STUDY DESIGN: A prospective observational study in scoliosis patients who were on
      noninvasive night ventilation for respiratory failure. OBJECTIVE: To report the
      results of spinal deformity correction in a group of patients with progressive
      scoliosis and rare forms of muscular dystrophy/myopathy with respiratory failure
      who were on nocturnal ventilatory support at the time of surgery. SUMMARY OF
      BACKGROUND DATA: This is the first study on the results of deformity correction
      in a series of patients on ventilatory support. MATERIALS AND METHODS: Eight
      patients (6 males, 2 females) presented with progressive scoliosis and
      respiratory failure. The mean age at surgery was 12 years (range, 8-15 years).
      The mean follow-up was 48 months (range, 12-80 months). Outcome measures include
      lung function (spirometry), overnight pulse oximetry, Cobb angles, duration of
      stay in Intensive care (ICU), and the total hospital stay. RESULTS: The mean stay
      in the ICU was 2.7 days (range, 2-5 days). The mean hospital stay was 14.2 days
      (range, 10-21 days). The mean preoperative Cobb angle was 70.2 degrees (55
      degrees -85 degrees ). This changed to 32 degrees (16 degrees -65 degrees ) after
      surgery (P = 0.0002). The mean vital capacity at the time of surgery was 20%
      (range, 13%-28%). The mean vital capacity of patients at last follow-up was 18%
      (range, 10%-31%). The desaturation noted on the preventilation overnight oximetry
      was reversed by nocturnal ventilation. All patients recovered well following
      surgery with no major cardiac or pulmonary complications. CONCLUSION: Patients
      with preexisting respiratory failure on nocturnal noninvasive ventilation can be
      safely operated for deformity correction. This can help to significantly improve
      their quality of life.

PMID- 17023859
TI  - Sagittal alignment of the spine and pelvis in the presence of L5-s1 isthmic lysis
      and low-grade spondylolisthesis.
AB  - STUDY DESIGN: A radiographic study of 82 patients with L5-S1 spondylolysis or
      spondylolisthesis of less than 50% displacement of L5 on S1. OBJECTIVE: To
      measure and describe the sagittal alignment of the spine and pelvis in patients
      with spondylolysis before the development of a large secondary deformity
      associated with progression of the spondylolisthesis. SUMMARY OF BACKGROUND DATA:
      Several publications have addressed the alignment of the spine and pelvis as an
      important factor in the occurrence, symptomatology, progression, and treatment of
      spondylolysis and spondylolisthesis. To our knowledge, this is the first report
      to systematically document the native sagittal alignment of affected patients and
      compare them to a large control population. MATERIALS AND METHODS: The sagittal
      alignment in this cohort of 82 patients was compared with a control population of
      160 patients without symptoms of back pain or radiographic abnormalities of the
      spine and pelvis that was the subject of a previous study. RESULTS: Patients with
      spondylolysis and low-grade spondylolisthesis demonstrate increased pelvic
      incidence, increased lumbar lordosis, but less segmental extension between L5 and
      S1 than in a normal population. CONCLUSIONS: These data suggest that differences
      in the sagittal alignment of the spine and pelvis may influence the biomechanical
      environment that results in the development of spondylolysis and progressive
      spondylolisthesis.

PMID- 17023860
TI  - Long-term outcome after posterolateral, anterior, and circumferential fusion for
      high-grade isthmic spondylolisthesis in children and adolescents: magnetic
      resonance imaging findings after average of 17-year follow-up.
AB  - STUDY DESIGN: A cross-sectional study to evaluate the long-term result of
      posterolateral (PLF), anterior (AF), and circumferential fusion (CF) for isthmic
      spondylolisthesis. OBJECTIVES: To assess the long-term effects of PLF, AF, or CF
      for high-grade isthmic spondylolisthesis on lumbar spine in children and
      adolescents by using MRI. SUMMARY OF BACKGROUND DATA: Short- and mid-term
      clinical and plain radiographic results of isthmic spondylolisthesis and of PLF,
      AF, and CF in severe slip are well documented. The long-term effect of the fusion
      on soft tissues, on the intervertebral discs inside and above fusion in
      particular, is, however, unclear. METHODS: Between 1977 and 1991, PLF (n = 21),
      AF (n = 22), or CF (n = 24) was performed on 67 patients (42 females, 25 males)
      with high-grade (slip > or =50%) isthmic spondylolisthesis. The average age of
      patients at the time of operation was 14.4 (range, 8.9-19.6) years. Clinical,
      spinal mobility and trunk strength in addition to MRI and plain radiograph
      examinations were performed on these patients after an average follow-up time of
      17.3 years (range, 10.7-26.0 years). RESULTS: Three (14%) patients in the PLF and
      AF groups, but none in the CF group, reported back pain often or very often at
      rest. The mean Oswestry Disability Index (ODI) was 9.7 (range, 0-62) in the PLF,
      8.1 (0-32) in the AF, and 2.3 (0-14) in the CF group (P < 0.05). The mean slip
      before surgery was 66% (range, 50%-100%) and at the last follow-up visit 66%
      (range, 26%-106%). Disc degeneration was most common in the PLF group (P =
      0.0014) and inside the fusion and in the lowest moving intervertebral disc spaces
      in all subgroups. Only 1 patient had an asymptomatic prolapse. In MR images, none
      of the patients had lumbar central canal stenosis inside or above the fusion. In
      contrast, the spinal canal was wide at the spondylolysis and spondylolisthesis
      level in 23 (34%) patients. Of the patients, 19 (28%) patients (32 neural
      foramens) had severe narrowing of the neural foramen with impingement of the
      nerve root. No patients had clinically confirmed L5 nerve root symptoms. Muscle
      degeneration was found in 29 (43%) of patients. Longer fusion and muscle
      degeneration, but not disc degeneration, were associated with lower performance
      in spinal mobility and trunk-strength measurement tests. CONCLUSIONS: The
      clinical outcome was best in the CF group as measured by ODI. Degenerative
      changes were most commonly found at the level of the slip and above the fusion
      level. The prevalence of disc prolapses was low. Spinal fusion for isthmic
      spondylolysis is not associated with central canal stenosis above the fusion.
      Radiologic nerve root stenosis was common but asymptomatic. Mild muscle atrophy
      was common.

PMID- 17023861
TI  - Incidence and recurrence of disabling low back pain and neck-shoulder pain.
AB  - STUDY DESIGN: A prospective cohort study with 1-year follow-up. OBJECTIVES: To
      assess incidence and recurrence of disabling low back (LBP) and neck-shoulder
      pain (NSP) in an industrial population, and to investigate the association with
      sex and job title during follow-up. SUMMARY OF BACKGROUND DATA: Epidemiologic
      data of LBP and NSP are sparse from developing countries. METHODS: All employees
      (18,031) in an Iranian industry were invited to participate in a baseline survey
      and followed for 1 year regarding new episodes of sickness absence due to LBP or
      NSP (disabling pain). RESULTS: The 1-year incidence of disabling LBP was 2.1% and
      of NSP 0.1%. Although the prevalence of LBP in females was higher than in males,
      the incidence disabling LBP were higher in males. Both prevalence and incidence
      of disabling LBP were high in unskilled workers. For NSP, managers had the
      highest reported prevalence, but incident cases happened only among office
      workers and unskilled workers. CONCLUSIONS: The incidence, especially for NSP, is
      much lower than from developed countries. To study prevalence, incidence and
      recurrence of LBP and NSP simultaneously leads to a better understanding of the
      natural pattern and distribution of LBP and NSP in a working population.

PMID- 17023862
TI  - Association between sciatica and microbial infection: true infection or culture
      contamination?
AB  - STUDY DESIGN: Discs were cultured during discectomy from patients with back pain,
      sciatica, and radiologic evidence of disc herniation causing nerve root
      compression. OBJECTIVE: To investigate the claim of culpability of bacteria in
      causing the local inflammatory process seen in patients with disc herniation and
      radiculopathy. SUMMARY OF BACKGROUND DATA: Bacteria have been cultured from
      intervertebral discs of patients with sciatica. An infectious etiology for
      sciatica could have a dramatic effect on treatment options for this common
      problem. METHODS: To minimize the risk of contamination, the surgeon performed
      processing and culturing procedures intraoperatively under stringent sterile
      conditions. Immediately following disc excision, the specimens were divided into
      4 pieces, and cultured in various aerobic and anaerobic culture mediums that were
      incubated for 2 weeks. RESULTS: The 120 specimens from 30 patients underwent
      bacterial culture growth: 116 were sterile, an 4 aerobic cultures (2 patients)
      grew coagulase-negative staphylococci, suggestive of contamination. CONCLUSIONS:
      These results refute the hypothesis that microbial infection plays a role in the
      pathogenesis of sciatica. It is possible that bacterial growth from discs
      reported in previous studies was at least partly related to contamination, which
      we painstakingly avoided by application of rigorous aseptic techniques.

PMID- 17023863
TI  - Work status as a predictor of surgical outcome of discogenic low back pain.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVES: To evaluate the role
      of work status as a predictor of outcome from anterior lumbar fusion. SUMMARY OF
      BACKGROUND DATA: Many psychosocial factors have been identified as predictors of
      chronic disability and of outcomes of surgery. Workers' Compensation and job
      satisfaction are two of the strongest and most evaluated factors. Work status at
      the time of intervention may also be relevant but has rarely been studied
      independently in patients having lumbar fusion. METHODS: A total of 106 patients
      with discogenic low back pain were treated by anterior lumbar interbody fusion.
      Patients were prospectively monitored by VAS, Roland Morris score, and work
      status. The influence of preoperative work status on outcome variables was
      assessed using odds ratios. A multivariate analysis was performed to assess
      influence of other confounding variables. Follow-up was a mean 29.7 months with
      95% greater than 1 year. RESULTS: Patients working at the time of surgery had a
      10.5 times greater likelihood of working at follow-up. Overall, only 43% of
      nonworkers were working at follow-up compared with 90% of patients who were
      working before surgery. This association was independent of Workers'
      Compensation, number of levels treated, and other demographic variables. A
      greater degree of pain relief was seen in patients working before surgery but not
      in function as measured by the Roland Morris score. CONCLUSION: These results
      show that patients with chronic low back pain should be encouraged to continue
      working up until surgery.

PMID- 17023864
TI  - Radiation exposure during pedicle screw placement in adolescent idiopathic
      scoliosis: is fluoroscopy safe?
AB  - STUDY DESIGN: With institutional review board approval, prospective data were
      collected during fluoroscopically guided pedicle screw placement. OBJECTIVE: To
      estimate a surgeon's radiation exposure with all screw constructs during surgery
      to repair idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: To our knowledge,
      there is no established consensus regarding the safety of radiation exposure
      during fluoroscopically guided procedures. METHODS: A surgeon was outfitted
      intraoperatively with a thermoluminescent dosimeter to estimate radiation
      exposure to his whole body and thyroid gland. RESULTS: The index surgeon is
      projected to receive 13.49 mSv of whole body ionizing radiation and 4.31 mSv of
      thyroid gland irradiation annually. The National Council on Radiation
      Protection's current recommendations set lifetime dose equivalent limits for
      classified workers (radiologists) at 10 mSv per year of life and at 3 mSv for
      nonclassified workers (spinal surgeons). At the levels estimated, a surgeon
      beginning his/her career at age 30 years would exceed the lifetime limit for
      nonclassified workers in less than 10 years. The National Council on Radiation
      Protection limits the single-year maximum safe dosage to the thyroid to 500 mSv;
      the yearly exposure estimated here is significantly less. CONCLUSIONS: The spinal
      surgeon's intraoperative radiation exposure may be unacceptable. Spinal surgeons
      should be considered classified workers and monitored accordingly. Methods to
      lower radiation dosage seem strongly indicated.

PMID- 17023866
TI  - Re: Korovessis P, Baikousis A, Zacharatos S, et al. Combined anterior plus
      posterior stabilization versus posterior short-segment instrumentation and fusion
      for mid-lumbar (L2-L4) burst fractures. Spine 2006; 31: 859-68.

PMID- 17023867
TI  - Efficacy and safety of immediate-release methylphenidate treatment for
      preschoolers with ADHD.
AB  - OBJECTIVE: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six
      center, randomized, controlled trial to determine the efficacy and safety of
      immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to
      5.5 years with attention-deficit/hyperactivity disorder (ADHD). METHOD: The 8
      phase, 70-week PATS protocol included two double-blind, controlled phases, a
      crossover-titration trial followed by a placebo-controlled parallel trial. The
      crossover-titration phase's primary efficacy measure was a combined score from
      the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney,
      and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was
      excellent response, based on composite scores on the Swanson, Nolan, and Pelham
      (SNAP) rating scale. RESULTS: Of 303 preschoolers enrolled, 165 were randomized
      into the titration trial. Compared with placebo, significant decreases in ADHD
      symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001)
      t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose
      for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the
      preschoolers (n=114) later randomized into the parallel phase, only 21% on best
      dose MPH and 13% on placebo achieved MTA-defined categorical criterion for
      remission set for school-age children with ADHD. CONCLUSIONS: MPH-IR, delivered
      in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD
      symptom scales in preschoolers compared to placebo, although effect sizes (0.4
      0.8) were smaller than those cited for school-age children on the same
      medication.

PMID- 17023868
TI  - Stimulant-related reductions of growth rates in the PATS.
AB  - OBJECTIVE: To investigate growth of children with attention-deficit/hyperactivity
      disorder (ADHD) in the Preschool ADHD Treatment Study (PATS) before and after
      initiation of treatment with methylphenidate at titrated doses (average, 14.2
      mg/day) administered three times daily, 7 days/week for asymptotically equal to1
      year. METHOD: The heights and weights of 140 children with ADHD were measured up
      to 29 times in the PATS protocol, starting at an average age of 4.4 years. The
      relationship between standard (z) scores and time on medication was examined
      using mixed-effect regression to estimate change in relative size (slope).
      RESULTS: Average relative size at baseline was significantly (p<.0001) greater
      than zero for z height (+0.45) and z weight (+0.78), indicating greater than
      expected height (by 2.04 cm) and weight (by 1.78 kg). During treatment, slopes
      were significantly (p<.0001) less than zero for z height (-0.304/yr) and z weight
      (-0.530/yr), indicating reduction of growth rates. For 95 children who remained
      on medication, annual growth rates were 20.3% less than expected for height (5.41
      cm/yr-6.79 cm/yr=-1.38 cm/yr) and 55.2% for weight (1.07 kg/yr-2.39 kg/yr=-1.32
      kg/yr). CONCLUSIONS: Risks of reduced growth rates should be balanced against
      expected benefits when preschool-age children are treated with stimulant
      medication.

PMID- 17023869
TI  - Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS).
AB  - OBJECTIVE: To describe the rationale and design of the Preschool ADHD Treatment
      Study (PATS). METHOD: PATS was a National Institutes of Mental Health-funded,
      multicenter, randomized, efficacy trial designed to evaluate the short-term (5
      weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in
      preschoolers with attention-deficit/hyperactivity disorder (ADHD). Three hundred
      three subjects ages 3 to 5.5 years old who met criteria for a primary DSM-IV
      diagnosis of ADHD entered the trial. Subjects participated in an 8-phase, 70-week
      trial that included screening, parent training, baseline, open-label safety lead
      in, double-blind crossover titration, double-blind parallel efficacy, open-label
      maintenance, and double-blind discontinuation. Medication response was assessed
      during the crossover titration phase using a combination of parent and teacher
      ratings. Special ethical considerations throughout the trial warranted a number
      of design changes. RESULTS: This report describes the design of this trial, the
      rationale for reevaluation and modification of the design, and the methods used
      to conduct the trial. CONCLUSIONS: The PATS adds to a limited literature and
      improves our understanding of the safety and efficacy of MPH in the treatment of
      preschoolers with ADHD, but changes in the design and problems in implementation
      of this study impose some specific limitations that need to be addressed in
      future studies.

PMID- 17023870
TI  - Pharmacogenetics of methylphenidate response in preschoolers with ADHD.
AB  - OBJECTIVE: The authors explored genetic moderators of symptom reduction and side
      effects in methylphenidate-treated preschool-age children diagnosed with
      attention-deficit/hyperactivity disorder (ADHD). METHOD: DNA was isolated from 81
      subjects in a double-blind, placebo-controlled, crossover methylphenidate
      titration. Parents and teachers completed ADHD symptom scales and side effect
      ratings for each of five randomly administered weekly conditions that included
      immediate-release methylphenidate 1.25, 2.5, 5.0, 7.5 mg and placebo given three
      times daily. Candidate genes hypothesized to influence stimulant effects or
      individual risks for ADHD were genotyped. RESULTS: Although the primary analysis
      did not indicate significant genetic effects, secondary analyses revealed
      associations between symptom response and variants at the dopamine receptor
      (DRD4) promoter (p=.05) and synaptosomal-associated protein 25 (SNAP25)
      allelesT1065G (p=.03) andT1069C (p=.05). SNAP25 variants were also associated
      with tics (p=.02), buccal-lingual movements (p=.01), and irritability (p=04).
      DRD4 variants were also associated with picking (p=.03). Increasing dose
      predicted irritability (p=.05) and social withdrawal (p=.03) with DRD4 variants.
      There were no significant effects for the dopamine transporter (DAT1).
      CONCLUSIONS: Emerging evidence suggests the potential for understanding the
      individual variability of response to and side effects of ADHD medications from
      the study of genetics, although additional research is required before these
      findings are proven to have clinical utility.

PMID- 17023872
TI  - Effects of aromatase inhibition on sexual function and well-being in
      postmenopausal women treated with testosterone: a randomized, placebo-controlled
      trial.

PMID- 17023873
TI  - Modeling women's health during the menopausal transition: a longitudinal
      analysis.
AB  - OBJECTIVE: There has been controversy about the relative effects on various
      health outcomes of hormonal, psychosocial, and lifestyle changes during the
      menopausal transition. In previous studies the risk factors for one particular
      health endpoint have been analyzed separately. Separate analyses do not provide
      an overall view of the relationships between all the variables or the relative
      importance of different factors. Thus, the objective of this study was to provide
      an overall analysis of the influence of hormonal changes during the menopausal
      transition on a range of health outcomes while simultaneously considering all the
      available predictors and all the endpoints and to test the hypothesis that prior
      health status predicts current health status. DESIGN: This was a 9-year
      prospective observational study of 438 Australian-born women, who at baseline
      were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews
      were conducted and fasting blood and physical measurements were performed
      annually. RESULTS: Main outcome measures were hormone levels, sociodemographic
      variables, attitudes and lifestyle variables, self-rated health and well-being,
      bothersome symptoms, coronary heart disease risk, bone mineral density, and
      sexuality. Data from 336 women, 77% of the original sample, were analyzed.
      Statistical modeling using structural equations showed that for all health
      endpoints, the prior level of that variable was the most important predictor.
      Declining levels of estradiol during the menopausal transition affected certain
      health outcomes: bone mineral density, coronary heart disease risk, vasomotor
      symptoms, vaginal dryness, and sexual response. Well-being is negatively affected
      by symptoms, hassles, and stress. Exercise has beneficial effects on hot flushes,
      well-being, body mass index, and coronary heart disease risk. Relationship
      factors and mood affect sexual response. CONCLUSIONS: This observational study
      provides a conceptual data-based framework for understanding changes in women's
      health during the natural menopausal transition.

PMID- 17023875
TI  - Bibliography current world literature.

PMID- 17023874
TI  - The relationship between physical activity and lipoprotein subclasses in
      postmenopausal women: the influence of hormone therapy.
AB  - OBJECTIVE: This study's objective was to determine if the association between
      physical activity and lipids and lipoprotein subclasses in postmenopausal women
      varies by hormone therapy (HT) use. DESIGN: The cross-sectional relationship
      between physical activity and lipid and lipoprotein subclass relationship was
      examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y)
      white and African American women from the Woman On the Move through Activity and
      Nutrition study. This study is a randomized clinical trial designed to test
      whether a lifestyle intervention will reduce subclinical cardiovascular disease
      measures. RESULTS: Hormone therapy users (n = 286) were significantly (P < 0.05)
      younger, less likely to be African American, reported higher levels of physical
      activity, large very low-density lipoprotein particles (VLDL-P), and medium high
      density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower
      levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL
      P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly
      associated with favorable lipoprotein and lipid levels, regardless of HT use.
      Some relationships were found to vary significantly by HT use. In nonusers, mean
      HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05,
      respectively) and total and small LDL-P were significantly lower (both P = 0.02)
      as activity increased. These relationship were not found in HT users.
      CONCLUSIONS: Physical activity was significantly related to some lipoprotein
      subclasses regardless of HT; however, several key lipoprotein subclasses were
      associated with higher levels of activity only among non-HT users.

PMID- 17023877
TI  - Pathology of the liver.
AB  - At the close of the 20th century, a selection of articles published in 1999 with
      relevance to liver pathology reflects the wealth of technological and
      intellectual progress made during the span of the century. Immunohistochemical
      staining for hepatitis B virus antigens focused attention on a correlation
      between cytoplasmic expression of core antigen in individuals with precore
      mutants and higher activity of hepatitis. Infection of ducklings with a
      presurface mutant strain of duck hepatitis B virus produced cytopathic liver cell
      damage. Fibrosing cholestatic hepatitis, originally described as an unusual form
      of recurrent hepatitis B after liver transplantation, has now been described in
      hepatitis C virus-positive patients with renal transplants. It may be related to
      the emergence or selection of hepatitis C virus quasispecies. In biliary tract
      disease, researchers investigated the canal of Hering as a possible source of
      hepatic stem cells, sporadic mutations in the JAGGED1 gene (involved in cell
      differentiation) in Alagille syndrome, and several models of nonsuppurative
      destructive cholangitis. Further work was accomplished on nonalcoholic
      steatohepatitis, including a proposal of a grading and staging system as well as
      its detection in workers exposed to volatile petrochemicals. Among hepatic
      neoplasms and proliferative disorders, epithelioid hemangioendothelioma,
      angiomyolipoma and Langerhans' cell histiocytosis received coverage in articles
      describing the diagnostic pathology in collected series of patients.

PMID- 17023878
TI  - Alcoholic liver disease.
AB  - Important mechanisms responsible for alcohol-induced liver injury include
      mitochondrial damage and loss of ATP, formation of acetaldehyde-and other
      aldehyde-protein adducts, release of reactive oxygen species (ROS) from
      mitochondrial electron transfer chain, CYP2E1 , and activated Kupffer cells
      (KCs); weakening of antioxidant defense systems; and increased intestinal
      permeability with endotoxemia. Endotoxin interacts with ethanol and/or
      acetaldehyde, and such interaction leads to a complex cascade of autocrine and
      paracrine pathways that involve the release of cytokines (proinflammatory, anti
      inflammatory, and mutagenic), chemokines, and eicosanoids. These pathways are
      mediated by activation of KCs, induction of proliferation, and other phenotype
      changes in hepatic stellate cells (HSCs) leading to transformation to
      myofibroblasts (the latter is responsible for fibrogenesis, chemotaxis, and
      contractility, therefore contributing to portal hypertension, angiogenic
      response, and release of additional cytokines), and stimulation of sinusoidal
      cells (SECs) to release adhesive molecules and cytokines. Recent data implicate a
      likely role of apoptosis as a mechanism of hepatocyte cell death in alcoholic
      liver disease.

PMID- 17023879
TI  - Inherited metabolic disease.
AB  - This review focuses on two genetic disorders of metal metabolism, genetic
      hemochromatosis and Wilson disease, and on the most common lysosomal storage
      disorder, Gaucher disease, for which recombinant enzyme replacement therapy is
      available. The discovery of the genes for these disorders has led to an explosion
      of new information about the function of these gene products and the
      identification of other proteins involved in their metabolism. These discoveries
      have altered our current diagnostic and therapeutic approaches to these disorders
      and have furthered our understanding of disease pathophysiology. New modalities
      being developed for future use include cell transplant and genetic replacement
      therapies.

PMID- 17023880
TI  - Drug-induced liver disease.
AB  - This year's review has been divided into five sections: The first describes the
      natural history of drug-induced liver disease, the second discusses the issue of
      placebo-related increases in liver-associated enzymes, the third describes agents
      newly reported to cause hepatic injury, the fourth discusses new reports of
      hepatic injury from established drugs, and the final section reviews the
      burgeoning field of hepatoprotection with clinical and experimental examples of
      agents used in the prevention and treatment of drug-induced liver disease, with
      acetaminophen as the major example.

PMID- 17023881
TI  - Cholestatic syndromes.
AB  - Continued advances in the field of liver cell biology and molecular biology have
      provided further insights into the normal physiology of bile secretion and the
      pathogenesis and therapy for cholestatic syndromes. Important new data have also
      been published about pathogenesis, clinical features, and treatment of primary
      biliary cirrhosis, primary sclerosing cholangitis, drug-induced cholestasis, and
      cholestatic syndromes caused by viral infections.

PMID- 17023882
TI  - Heptaobiliary infections.
AB  - Although cholangitis is the most prevalent hepatobiliary infectious process,
      liver abscess represents the most serious and conspicuous hepatobiliary
      infection. Amebic liver abscess typically occurs in individuals from endemic
      areas or those traveling to endemic areas. It is associated with an excellent
      prognosis when managed expediently with antiamebic antibiotics. Recent reports
      emphasize a possible association between amebic liver abscess and HIV infection.
      Drainage or surgery for amebic liver abscess is rarely necessary. In contrast,
      pyogenic liver abscess is associated with significant morbidity and mortality,
      although the prognosis of patients with this hepatobiliary infection has improved
      in recent years. Pyogenic liver abscess occurs most often in patients without
      identifiable predisposing factors, but when identified, they are most often
      biliary tract-related. Management of pyogenic liver abscess has historically been
      surgical, but in recent years, there has been a dramatic shift toward noninvasive
      management, particularly involving strategies based on percutaneous drainage
      techniques.

PMID- 17023883
TI  - Viral hepatitis.
AB  - Viral hepatitis accounts for most liver diseases seen in hepatology practice. In
      the past year studies have been focused on uncovering the basic mechanisms of
      viral-cellular interactions, the knowledge of which will contribute to more
      effective treatment. Hepatitis A virus outbreaks still occur, even in the most
      developed countries, which points to the need for more comprehensive vaccination
      measures. Lessons learned from the treatment of HIV with combination antiviral
      therapies are being applied to both chronic hepatitis B and C. Progress has been
      made toward better understanding of viral kinetics and the quasi-species of
      hepatitis C virus with new and more sensitive diagnostic methods. Several
      therapeutic protocols are emerging to identify and tailor the management approach
      in various subsets of the population. Although posttransplantation hepatitis B
      has been more effectively managed with lamivudine therapy, no major advances have
      been accomplished in the treatment of recurrent hepatitis C among transplant
      recipients. Major advances in the field of viral hepatitis including A to E and
      TT viruses during the past year are highlighted.

PMID- 17023884
TI  - Autoimmune liver disease.
AB  - Regional differences in the manifestations of autoimmune hepatitis underscore the
      importance of genetic and/or environmental factors in its expression. The -308
      polymorphism of TNF-A increases susceptibility to type 1 autoimmune hepatitis;
      HLA DRB1*13 is an important risk factor in South America; and DRB1*07
      characterizes type 2 autoimmune hepatitis. Minocycline and mesalazine can trigger
      the disease, and interferon therapy can accentuate autoimmune manifestations.
      Autoimmune cholangitis in Japan is similar to primary biliary cirrhosis, and
      assays for carbonic anhydrase II lack diagnostic specificity. Perinuclear
      antineutrophil cytoplasmic antibodies are reactive to diverse nuclear antigens,
      but high mobility nonhistone chromosomal proteins may be important targets in
      autoimmune hepatitis. T cells can cross-react with viral and host peptides, and
      the candidacy of glutathione S-transferases as target autoantigens has been
      weakened. A murine model of PBC will be useful in studying mechanisms of
      autoreactivity, and cyclosporine has shown promise in the treatment of children
      with autoimmune hepatitis. Recurrence after liver transplantation is common, and
      it may require retransplantation. The human transplantation model will be
      valuable in understanding the host-and organ-specific contributions to disease
      expression.

PMID- 17023885
TI  - Pediatric liver disease.
AB  - Pediatric hepatology is no different than any other pediatric specialty. The
      prime objective is either to cure disease or to minimize its impact on the child.
      The result will be that children with chronic liver disease will become adults
      with chronic liver disease, and the long-term follow-up of pediatric liver
      disease will pass out of the hands of pediatricians. For this to happen
      effectively, continuous reappraisal of outcome data will be required to optimize
      treatment at all stages. It will also become important for physicians in adult
      practice to follow the progress being made in the management of pediatric liver
      disease.

PMID- 17023886
TI  - Hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) appears to be declining in Taiwan
      and potentially in other high-prevalence areas as a consequence of vaccination
      for hepatitis B virus (HBV). However, there is evidence that the incidence of HCC
      is increasing in North America and Europe. This appears to be related to the
      increasing prevalence and duration of hepatitis C virus (HCV) infection in these
      countries. There is also growing evidence to support an increase in the risk of
      HCC in patients with HCV who are coinfected with occult HBV (patients who have
      lost HBV surface antigen but still have detectable HBV DNA either in blood or
      liver). Occult HBV infection in patients with HCV may be more common than
      previously thought, and HCC that occurs in this setting appears to have a worse
      prognosis. There is continuing interest in the effect of interferon therapy on
      the incidence of HCC in patients with HCV. Several studies from Japan have shown
      a benefit in patients without cirrhosis, although there are a number of
      potentially confounding variables that may partly explain these results.
      Prospective randomized studies are needed to investigate this important question.
      The molecular biology of HCC and the events of malignant transformation in the
      liver continue to be areas of intense study. Recently, there has been
      considerable interest in telomeres, the repeat units on the ends of chromosomes,
      and the enzyme that maintains these, telomerase. Telomeres shorten with each cell
      division and can be used to determine the number of divisions a cell has
      undergone. Eventually they reach a critical length, with further loss resulting
      in cellular senescence. Telomerase restores telomere length and may help
      malignant cells escape senescence. Nearly all HCCs have telomerase activity and
      assessments of telomeres and telomerase may be clinically useful.

PMID- 17023887
TI  - Portal hypertension.
AB  - Cirrhosis represents the end-stage of any chronic liver disease. Two major
      syndromes result from cirrhosis-portal hypertension and hepatic insufficiency.
      Additionally, vasodilatation and the hyperdynamic circulation are hemodynamic
      abnormalities typical of cirrhosis and portal hypertension. Complications of
      cirrhosis occur as a consequence of a combination of these factors.
      Gastroesophageal varices result almost solely from portal hypertension, although
      the hyperdynamic circulation contributes to variceal growth and hemorrhage.
      Ascites results from sinusoidal hypertension and sodium retention, which is, in
      turn, secondary to vasodilatation and activation of neurohumoral systems.
      Hepatorenal syndrome also results from severe peripheral vasodilatation that
      leads to renal vasoconstriction. Another complication of cirrhosis, portosystemic
      encephalopathy, is a consequence of both portal hypertension (shunting of blood
      through portosystemic collaterals) and hepatic insufficiency. In this article,
      recent advances in pathophysiology and management of the complications of
      cirrhosis and portal hypertension are reviewed.

PMID- 17023888
TI  - Liver transplantation.
AB  - Survival after liver transplantation has steadily improved, in part because of
      newer immunosuppression, which may offer decreased long-term side effects.
      Reduction of steroids early in the course of transplant continues to be a goal,
      with satisfactory results in terms of both risk of rejection and reduction of
      side effects. Dominating the literature and the press in 1999 was the controversy
      surrounding the way in which livers are allocated. Regulation by the federal
      government was proposed to change the way the United Network of Organ Sharing
      distributes and allocates livers. Prompted by the shortage of organs, living
      donor liver transplantation has blossomed. Continued experience in pediatric
      patients has shown excellent survival rate and quality of life. In adults,
      further experience is being gained with respect to the use of right lobes for
      transplantation. Early data suggest that this is a potential alternative to
      cadaveric transplantation in adults, with acceptable risk to the donor. Despite
      advances made in improving the technical aspects of transplantation, recurrent
      disease remains a significant issue. Lamivudine appears to be a potent inhibitor
      of hepatitis B virus DNA replication after liver transplantation, although
      resistance remains a significant problem. Further review of transplantation for
      hepatitis C virus is encouraging, with excellent five-year survival rate.
      However, studies evaluating the evolution of fibrosis in these patients throw
      caution on those results, showing increased progression to cirrhosis over time.
      Further follow-up of these patients is needed to more accurately assess long-term
      impact of hepatitis C on morbidity and mortality rates after liver
      transplantation.

PMID- 17023890
TI  - Intracranial vascular surgery.
AB  - PURPOSE OF REVIEW: To review the recent literature on intracranial vascular
      surgery, to summarize the main findings, and to discuss the impact of these
      findings on clinical practice. RECENT FINDINGS: Three areas of vascular
      neurosurgery literature have recently generated significant interest, controversy
      and heated debate: (1) The International Study of Unruptured Intracranial
      Aneurysms studied the natural history and treatment options of unruptured
      aneurysms, and reported surprisingly low aneurysm rupture rates for small
      asymptomatic aneurysms. The study also reported favorable morbidity rates for
      endovascular treatment compared with surgical treatment of unruptured aneurysms.
      (2) The International Subarachnoid Aneurysm Trial compared endovascular and
      surgical treatments for ruptured intracranial aneurysms. The study concluded that
      the outcome in terms of survival free of disability at one year was significantly
      better with endovascular coiling. (3) The Intraoperative Hypothermia for Aneurysm
      Surgery Trial compared intraoperative hypothermia and normothermia for potential
      neuroprotection during neurovascular procedures. Preliminary results suggest no
      difference between the treatments. SUMMARY: The International Study of Unruptured
      Intracranial Aneurysms and the International Subarachnoid Aneurysm Trial have
      provided data on the natural history of unruptured intracranial aneurysms and on
      the morbidity and mortality of surgical and endovascular treatments for
      intracranial aneurysms. Although morbidity rates of endovascular therapy compare
      favorably with those of surgery, long-term data on the efficacy of endovascular
      coiling of aneurysms are needed to assess the overall risk-benefit ratio of these
      therapies.

PMID- 17023891
TI  - Anaemia and the brain.
AB  - PURPOSE OF REVIEW: This article reviews the physiological and pathophysiological
      effects of anaemia on the brain, focusing on the hypothesis that anaemia-induced
      cerebral hypoxia contributes to anaemic cerebral dysfunction and injury. It also
      reviews evidence that the regulated increase in cerebral blood flow observed
      during anaemia represents a compensatory neuroprotective mechanism invoked to
      optimize cerebral oxygen delivery, thereby protecting the brain from hypoxic
      injury. RECENT FINDINGS: Severe anaemia, or low haematocrit, has been associated
      with cognitive dysfunction, impaired cerebral vascular regulation, neurological
      injury, and increased mortality, which suggests that the brain is vulnerable to
      anaemia-induced injury. Reduced cerebral tissue oxygen tension has been measured
      directly at haemoglobin concentrations near 35 g/l, suggesting that hypoxia may
      contribute to anaemic cerebral injury. A demonstration of increased hypoxic
      cerebral gene expression, including neuronal nitric oxide synthase, may provide a
      more sensitive means of determining the minimum haemoglobin concentration at
      which anaemia-induced cerebral hypoxia can be detected. The measurement of
      increased cerebral cortical neuronal nitric oxide synthase messenger RNA and
      protein levels in rats, at haemoglobin concentrations between 50 and 60 g/l,
      suggests that cerebral hypoxia occurred at these higher haemoglobin
      concentrations. Mechanisms regulating anaemic cerebral vasodilation and increased
      cerebral oxygen delivery, including nitric oxide, require further elucidation to
      establish their role in protecting the brain during anaemia. SUMMARY:
      Characterization of mechanisms of anaemia-induced cerebral injury will contribute
      to the development of optimal therapeutic strategies for anaemic patients. Such
      strategies would include a clearer definition of transfusion triggers based on
      physiological endpoints. The overall goal of these efforts would be to minimize
      morbidity and mortality associated with anaemia.

PMID- 17023892
TI  - Managing elevated intracranial pressure.
AB  - PURPOSE OF REVIEW: Elevated intracranial pressure is one of the major
      deteriorating factors in patients with intracerebral lesions. Therefore, every
      year many experimental and clinical studies are performed to identify the best
      method for managing elevated intracranial pressure in head-injured patients. The
      current review summarizes the most important recent findings for the treatment of
      increased intracranial pressure. RECENT FINDINGS: The currently most discussed
      treatments of elevated intracranial pressure are the use of hypertonic saline,
      which seems to be equal to mannitol, the use of hypothermia, and the performance
      of decompressive craniectomy. SUMMARY: The treatment strategy to manage increased
      intracranial pressure includes decisions about anaesthetics, ventilation, head
      and body position, hypothermia, the use of osmotic drugs and surgical procedures.
      Propofol seems to be suitable for the sedation of patients with elevated
      intracranial pressure. Sudden increases in intracranial pressure can be treated
      using hyperosmotic agents, high-dose thiopental, or short episodes of mild
      hyperventilation. Surgical decompression of the cranium seems to improve the
      outcome in patients below the age of 50 years, especially children.

PMID- 17023893
TI  - Endoscopic and stereotactic neurosurgery.
AB  - PURPOSE OF REVIEW: Review of the anesthetic considerations for neuroendoscopy and
      stereotactic procedures. RECENT FINDINGS: Minimally invasive procedures are
      increasingly applied in novel ways in the diagnosis and treatment of neurological
      pathologies. Endoscopic third ventriculostomy, endoscopic shunt revisions and
      drainage of intraventricular hematoma using a neuroendoscope have become routine
      neurosurgical procedures. Stereotaxis has expanded its scope from simple brain
      biopsy to functional neurosurgery and psychiatry. While these procedures are
      'minimally invasive', perioperative critical events may still occur. SUMMARY:
      Vigilance in preoperative assessment and intraoperative monitoring is essential
      in minimizing perioperative morbidity and mortality in patients undergoing
      neuroendoscopic and stereotactic procedures.

PMID- 17023894
TI  - Neurosurgery for the treatment of epilepsy.
AB  - PURPOSE OF REVIEW: Epilepsy is a common condition that is estimated to afflict
      0.5-1.0% of the world's population. Frequently commencing in childhood, it is
      often associated with life-long disability. Approximately one-third of patients
      with epilepsy are refractory to antiepileptic drug therapy and many of these
      patients are candidates for surgical treatment. A growing body of evidence
      supports the safety and efficacy of surgery for the treatment of selected
      patients with epilepsy. Little information is available in the anesthesia
      literature regarding the presurgical assessment of candidates for surgical
      treatment. RECENT FINDINGS: The presurgical identification of suitable candidates
      involves a multidisciplinary approach to assessment. Recent advances,
      particularly in neuroimaging techniques, are dramatically enhancing the capacity
      to accurately identify patients who are most likely to benefit from surgery.
      Epilepsy surgery is underused worldwide and in developed countries. In view of
      current efforts to increase opportunities to provide surgical treatment to more
      patients and to offer surgery earlier in the course of the disorder, the number
      of patients requiring specialized perioperative anesthetic care is expected to
      increase. SUMMARY: This article provides anesthesiologists with an overview of
      the assessment process, investigation techniques and current rationale that
      influence the selection of appropriate candidates for surgical treatment and the
      associated need for specialized anesthetic care.

PMID- 17023895
TI  - Interventional neurophysiologic monitoring.
AB  - PURPOSE OF REVIEW: Intraoperative neurophysiologic monitoring provides useful
      information on the functional status of the nervous system. This review focuses
      on recently published data concerning the impact of monitoring on patient
      outcome. RECENT FINDINGS: There is level I evidence to support the use of
      bispectral index monitoring to prevent awareness during anesthesia in high-risk
      patients. A number of randomized trials have shown that monitoring-guided
      anesthesia using the bispectral index or other devices will expedite recovery and
      improve perioperative drug utilization. There are also preliminary reports
      suggesting that anesthesia dictated by bispectral index monitoring may alter long
      term outcome and reduce mortality. In surgical procedures, however, it is less
      clear whether neurophysiologic monitoring will improve patient outcome.
      Currently, the majority of data are derived from respective case series.
      Nonetheless, monitoring with somatosensory evoked potential has been shown to
      reduce postoperative neurologic deficits after spinal surgery. There is also
      evidence to suggest that electromyography and motor evoked potential are
      essential complements to somatosensory evoked potential for monitoring of spinal
      cord surgery. SUMMARY: Brain monitoring facilitates anesthetic drug
      administration. An increasing number of neurosurgical procedures will require
      some form of intraoperative neurophysiologic monitoring to achieve higher degrees
      of safety and accuracy. In many instances, the data derived from monitoring will
      guide and influence surgical decisions. In this context, neurophysiologic
      monitoring should be regarded as interventional.

PMID- 17023896
TI  - Anesthetics and cerebral metabolism.
AB  - PURPOSE OF REVIEW: This review focuses on the utilization of the effects of
      general anesthetics on cerebral metabolism as revealed by imaging for therapeutic
      and preventive purposes, for understanding mechanisms of anesthetic action, and
      for elucidating mechanisms of cerebral processing in humans. RECENT FINDINGS:
      General anesthetics suppress cerebral metabolism significantly. This effect has
      been used for neuroprotection during inadequate cerebral blood flow. With the
      advent of noninvasive imaging techniques, this suppression has also been used to
      image and map the sites of anesthetic action in the living human brain. Volatile
      agents, intravenous anesthetics, and analgesics have all begun to be explored
      using mostly positron emission tomography. The ability of anesthetics to change
      global baseline brain metabolism has created the opportunity to examine the
      relevance of global baseline (resting) brain activity in terms of region-specific
      cerebral processing. SUMMARY: Anesthetics experimentally appear to be useful for
      neuroprotection, at least during the early post-ischemic period. Identification
      of the cerebral sites of anesthetic action by in vivo human brain imaging
      provides new insights into the mechanism of action of these agents. Anesthetic
      related manipulation of baseline brain metabolism demonstrates the significant
      contribution of this global activity to regional cerebral processing.

PMID- 17023897
TI  - Lower extremity nerve blocks.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present the most important
      recent studies into the clinical use of peripheral nerve blocks for anesthesia
      and postoperative analgesia of the lower limb surgery. RECENT FINDINGS: There is
      increasing interest in lower extremity peripheral nerve blocks because of their
      potential advantages and concerns over interactions of centroneuraxis blocks and
      anticoagulants. Several authors have studied different approaches to the blockade
      of peripheral nerves with their advantages or disadvantages. Continuous
      peripheral nerve blocks have showed prolonged analgesia and great patient
      satisfaction with low side effects. Recent imaging techniques (e.g. ultrasound,
      magnetic resonance, tomography scans) have been developed to improve the
      performance of lower peripheral nerve blocks. Finally, complications of these
      techniques have been examined. SUMMARY: Introduction of new methods and
      techniques are increasing and improving the use of lower peripheral nerve blocks.
      These techniques are gaining interest after the important increase of the lower
      molecular weigh heparins.

PMID- 17023898
TI  - Image-guided techniques for peripheral nerve blocks.
AB  - PURPOSE OF REVIEW: Success of plexus nerve block is most dependent upon the
      correct positioning of the local anaesthetic solution within proximity to the
      corresponding nerve trunk. With the aim of verifying the close approximation of
      needle and nerve, and increasing the corresponding success rate, in the course of
      the history of regional anaesthesia, and in addition to the classical methods
      like seeking of paraesthesia, different mechanical aids have been used for nerve
      detection. In the last two decades, important medical diagnostic and therapeutic
      advances in imaging technology have been presented. In this review we will
      analyse the role such imaging diagnostic procedures will play in regional
      anaesthesia practice. RECENT FINDINGS: Last developments in the field have
      produced increased interest in the application of imaging techniques in regional
      anaesthesia. Of special interest are ultrasound and low radiation x-ray
      techniques for location of the needle in relation with neural structures.
      SUMMARY: In this paper we will analyse which imaging techniques are of relevance
      to anaesthesia in terms of clinical outcome, research and teaching of regional
      anaesthetic techniques, and the clinical impact of such imaging techniques upon
      anaesthesia practice.

PMID- 17023899
TI  - Nerve injury and regional anaesthesia.
AB  - PURPOSE OF REVIEW: In recent years there has been a renewed interest in regional
      anaesthesia, particularly peripheral nerve blockade, not only to improve the
      patient's well being, but also to meet the requirements of modern orthopaedic
      surgery. Nerve injury in this context is the complication most feared by the
      patient, the anaesthesiologist and the surgeon. RECENT FINDINGS: To date, data
      dealing with the incidence of nerve injury in regional anaesthesia have almost
      exclusively been retrieved from close claims analysis. Recently, prospective,
      well controlled studies have shown that severe neurologic complications rarely
      occur: for the upper extremity, an incidence of 0.2-1% has been reported. New
      insights into the mechanisms of local anaesthetic neurotoxicity have demonstrated
      that ropivacaine has the least potential for neurotoxicity. Administration of the
      lowest possible concentrated solution of local anaesthetic is likely to be even
      less neurotoxic. The role of local anaesthetics in the development of apoptosis
      is nowadays well recognized. The consequences of other factors, such as nerve
      stretching and compression, in the pathology of nerve damage are emphasized.
      SUMMARY: Significant advances have been made in regional anaesthesia in the past
      10 years. The introduction of catheter techniques has cleared the way for better
      regional anaesthetic and analgesic blocks. Studies dealing with placement of
      perineural catheters show that the catheter does not increase neurological
      complications. Properly performed, regional anaesthesia is a safe form of
      anaesthesia and the benefits far outweigh the risks.

PMID- 17023900
TI  - Transient neurological syndrome: does it really exist?
AB  - PURPOSE OF REVIEW: Subarachnoid injection of local anesthetics has been related
      to the appearance of transient neurological symptoms (called transient neurologic
      syndrome), as reflected by a number of clinical reports showing their incidence
      in clinical practice. However, the etiology of this syndrome is virtually
      unknown, as is the number of factors implicated in its development. This review
      will attempt to clarify this entity and its relationship with spinal anesthesia.
      RECENT FINDINGS: Intrathecal administration of local anesthetics is known to
      increase glutamate concentration in cerebrospinal fluid and histopathologic
      changes of motor neurons in the lumbar spinal cord, suggesting damage of dorsal
      and ventral roots. In-vitro studies of cultured neurons exposed to different
      concentrations of local anesthetics have shown changes in growth of cones and
      neurites, which may be related to transient neurologic syndrome. SUMMARY: The
      latest studies show biochemical and anatomopathologic changes that support the
      structural basis of the existence of transient neurologic syndrome. In the
      authors' view, transient neurologic syndrome could represent the lower end of a
      spectrum of local anesthetic toxicity. Recent findings demonstrate that nerve
      membrane damage induced by highly concentrated local anesthetics such as
      lidocaine, tetracaine, dibucaine and procaine may generate irreversible neural
      injury. Still further studies are needed to establish the relationship between
      morphological changes induced in vitro and the occurrence of clinical symptoms.

PMID- 17023901
TI  - Regional anesthesia and anticoagulation.
AB  - PURPOSE OF REVIEW: Patients receiving perioperative anticoagulation are a
      challenge for anesthesiologists when regional anesthesia would be a beneficial
      component of the anesthetic plan. Newly approved antithrombotic drugs maintain
      the need for updated review articles and recommendations. RECENT FINDINGS: Due to
      the very low incidence of bleeding complications, guidelines are solely based on
      retrospective analyses of case reports and pharmacological considerations. Hence,
      they should not be taken as evidence-based 'cook books'. Recommendations of well
      established anticoagulants like heparin and non-steroidal antiinflammatory drugs
      may have a solid basis. However, the lack of data on new antithrombotic drugs
      including GII/GIIIA antagonists, factor X and thrombin-inhibitors requires a more
      conservative approach when regional anesthesia is considered. Current literature
      emphasizes postoperative monitoring; clear recommendations of its performance,
      however, are missing. SUMMARY: Decisions to perform regional anesthesia in
      patients under anticoagulation should always be made on an individual risk
      benefit assessment. A vigilant preoperative evaluation of the patient's
      medication and physical findings are as important as awareness of postoperative
      plans for anticoagulation.

PMID- 17023902
TI  - Regional anesthesia and perioperative outcome: what is new?
AB  - PURPOSE OF REVIEW: This review of the most recent publications is aimed to look
      at the current developments regarding the effects of regional anesthesia on
      perioperative outcome. RECENT FINDINGS: The debate continues on whether regional
      anesthesia and analgesia improve outcome or not. Researchers are still divided in
      their views. While previous meta-analyses are more favorable, more recent trials
      are rather on the con side. In an attempt to lessen heterogeneity, meta-analyses
      have now incorporated data from more recent trials to perform subgroup analyses.
      Such analyses persistently show the same positive results. The established
      outcome effects of regional anesthesia are mostly due its ability to provide
      superior analgesia, its ability to reduce the perioperative stress response and
      subsequent physiologic perturbations, and its ability to reduce pulmonary
      complications. Its potential to prevent cardiac morbidity in patients undergoing
      coronary artery bypass grafting is investigated further by looking at valuable
      specific biological markers like troponin I and natriuretic peptides. Intrathecal
      opioids do not seem to improve outcome, unlike the intrathecal local anesthetics.
      The latter improve outcome presumably by blocking the surgical stress response.
      In contrast, opioids, non-steroidal antiinflammatory drugs and cyclooxygenase-2
      inhibitors have been shown not to impact outcome presumably by not being able to
      interfere with the stress response. The safety and efficacy of epidural or spinal
      anesthesia for spinal surgery continue to be demonstrated by current studies.
      SUMMARY: Despite the controversies, the numerous potential benefits and
      advantages of regional anesthesia are keys to its continued popularity. With
      constant search for new scientific clues by improving experimental designs,
      valuable evidence slowly unfolds. Regional anesthesia certainly takes a leading
      role in the current trends for a multimodal approach of perioperative pain
      management.

PMID- 17023903
TI  - Recent insights into the pharmacokinetics of spinal opioids and the relevance to
      opioid selection.
AB  - PURPOSE OF REVIEW: Spinal opioid administration was introduced into clinical
      practice nearly 25 years ago in the hope of producing intense spinal analgesia
      that was devoid of the dose-limiting side effects associated with systemic opioid
      administration. While spinal opioid administration can clearly be an effective
      analgesic technique, there is a widespread misconception that any opioid
      administered epidurally or intrathecally will produce analgesia by a selective
      spinal mechanism. This is simply not true; multiple opioids that are commonly
      administered spinally produce analgesia by uptake into the systemic circulation
      with subsequent redistribution to brainstem opioid receptors. In an effort to
      help clinicians understand why some opioids are not suitable for selective spinal
      analgesia, this review describes recent insights into the fate of intrathecally
      and epidurally administered opioids. RECENT FINDINGS: A series of animal studies
      published over the last 4 or more years have provided the first measurements of
      opioid concentration in the epidural space, intrathecal space, spinal cord and
      peri-spinal tissues following intrathecal and epidural opioid administration.
      These studies characterize, for the first time, the factors governing the rate
      and extent to which different opioids redistribute from the epidural and
      intrathecal spaces to reach target opioid receptors in the spinal cord dorsal
      horn. The findings indicate that increasing lipid solubility decreases the spinal
      cord bioavailability of spinally administered opioids. SUMMARY: These animal data
      help to explain multiple clinical studies that have demonstrated that the
      analgesic effect of spinally administered lipid-soluble opioids is due in part,
      if not exclusively, to uptake into plasma and distribution to brainstem opioid
      receptors.

PMID- 17023904
TI  - Morphine metabolites as novel analgesic drugs?
AB  - PURPOSE OF REVIEW: Morphine metabolites have attracted continuing interest for
      their contribution to the desired and unwanted effects of morphine. Among the
      metabolites of morphine, morphine-6-glucuronide has been given most scientific
      attention. It accounts for 10% of the morphine metabolism, acts as an agonist at
      mu-opioid receptors and exerts antinociceptive effects. This review summarizes
      the recent findings on morphine-6-glucuronide and discusses its potential use as
      an analgesic. RECENT FINDINGS: Morphine-6-glucuronide has a very long delay
      between the time course of its plasma concentrations and the time course of its
      central nervous effects, with 6-8 h probably the longest transfer half-life
      between plasma and effect site of all opioids administered in humans. This
      complicates the control of morphine-6-glucuronide therapy when used as an
      intravenous analgesic, and the long duration of action confers no advantage over
      other opioids because long-lasting opioid analgesia can be readily obtained with
      sustained release formulations of other opioids. During acute treatment, however,
      morphine-6-glucuronide appears to be sufficiently potent to exert peripheral
      analgesic effects, without exerting major central nervous opioid side effects for
      a short period of time. The side effects profile does not clearly separate
      morphine-6-glucuronide from morphine, with reports of similar side effects. There
      are contrasting reports, however, about similar or less respiratory depression
      and other side effects compared with morphine after systemic injection. SUMMARY:
      Morphine-6-glucuronide might qualify as an analgesic but it has several
      pharmacological properties that make it far from ideal for therapeutic use.
      Whether it will be a useful addition to the currently established analgesics has
      yet to be demonstrated.

PMID- 17023905
TI  - Postoperative pain and quality of recovery.
AB  - PURPOSE OF REVIEW: Quality of recovery is recognized as a valid and important
      outcomes measurement in clinical care and research. The increasing interest in
      evaluating quality of recovery reflects the overall increased interest in patient
      focused assessments. Assessment of quality of recovery incorporates measuring
      many dimensions or domains including physiologic endpoints, adverse events and
      psychosocial status. Unlike 'traditional' outcomes that focus on major morbidity
      and mortality, quality of recovery assesses 'nontraditional' outcomes focused
      around patient-oriented endpoints. By adversely influencing the many domains
      assessed by quality of recovery, postoperative pain may have a general
      detrimental effect on quality of recovery. RECENT FINDINGS: Studies utilizing
      validated instruments to assess quality of recovery have revealed that different
      levels of postoperative pain may differentially affect quality of recovery. In
      addition, quality of recovery in the immediate postoperative period may predict
      long-term quality of life. SUMMARY: Higher levels of postoperative pain typically
      correlate with a decrease in quality of recovery. Different analgesic techniques
      and regimens may differentially influence quality of recovery, with preliminary
      evidence suggesting that some regional analgesic techniques may provide superior
      quality of recovery, quality of life and patient satisfaction. Further studies
      are needed to elucidate the effects of different analgesic techniques on quality
      of recovery.

PMID- 17023906
TI  - Neurogenic painful inflammation.
AB  - PURPOSE OF REVIEW: Neurogenic inflammation results from the release of
      neuropeptides from peripheral nerve terminals. This secretion can be induced by
      two mechanisms: activation of afferent sensory nerves (e.g. by disease processes
      or experimentally by electrical stimulation) or activation of receptors expressed
      on peripheral nerve terminals. While the role of these mechanisms in the
      regulation of inflammation is well described, its significance for the generation
      of pain is much less clear and will be examined in this review. RECENT FINDINGS:
      Activation of two receptors on peripheral sensory neurons (i.e. transient
      receptor potential vanilloid-1 channel and proteinase activated receptor-2) has
      been shown to induce neurogenic inflammation. Interference with this activation
      can ameliorate pain, but it remains uncertain whether this effect is indeed
      mediated by blockage of neurogenic inflammation. Two human diseases (complex
      regional pain syndrome and migraine) are believed to result from aberrant
      neuronal activation. In complex regional pain syndrome, studies in human patients
      and in a recently established animal model do not support a role for neurogenic
      inflammation in pain. In migraine, antagonists to the receptor for calcitonin
      gene related peptide ameliorated headache and could be the first conclusive
      evidence for the role of neurogenic inflammation in the generation of pain.
      Lastly, spinal mechanisms also appear to regulate immune cell recruitment to a
      peripheral site and seem to interfere with antinociception. SUMMARY: While
      considerable experimental and clinical evidence supports the existence of
      neurogenic inflammation, it is less clear whether this process plays an important
      role in the generation of pain.

PMID- 17023907
TI  - Current world literature.

PMID- 17023910
TI  - The molecular basis of colorectal carcinogenesis.
AB  - The development of colorectal neoplasms can be characterized by an ordered series
      of events that are referred to as the dysplasia-carcinoma sequence. These
      histologic changes occur as a result of genetic alterations in proto-oncogenes
      and tumor-suppressor genes. This review emphasizes important studies
      characterizing the role of four genes, APC, Cox-2, DCC/Smad4, and the mismatch
      repair genes, in colorectal carcinogenesis.

PMID- 17023911
TI  - Cancer chemoprevention.
AB  - Chemoprevention is defined as nutritional or pharmaceutical interventions
      designed to prevent or delay cellular transformation. Over the last year, the
      great excitement and interest in the mechanism, epidemiology, and preclinical and
      clinical chemopreventive effects in the lower intestine of nonsteroidal anti
      inflammatory drugs continues and is reflected in the large number of publications
      on this topic. Investigators from Japan and the United States published
      preclinical studies of a number of new compounds derived from citrus products and
      Asian foods and spices with potential clinical promise. Disappointment in the
      lack of efficacy of epidemiologically predicted micronutrient chemopreventives
      continues with the publication of an additional clinical trial. This
      disappointment is tempered by a potentially important observation suggesting that
      pharmacologic approaches of measuring an individual's food intake and assessing
      individual variation in disposition, bioavailability, and metabolism of
      micronutrients might allow for more accurate and individualized nutritional
      chemopreventive approaches in the future.

PMID- 17023912
TI  - Evolving concepts in irritable bowel syndrome.
AB  - Converging evidence from investigations of the peripheral and central aspects of
      bidirectional brain-gut interactions is beginning to shape a pathophysiological
      model of irritable bowel syndrome (IBS) and related functional gastrointestinal
      (GI) disorders. This neurobiological model includes alterations in autonomic,
      neuroendocrine, and pain modulatory mechanisms. The frequent association of IBS
      and other functional GI disorders with co-morbid affective disorders and temporal
      association of symptom exacerbation with psychosocial or physical stressors are
      consistent with alterations in the neurobiological mechanisms underlying the
      central stress response. Renewed interest in drug development for IBS has
      resulted in development of instruments for the better assessment of the impact of
      global symptoms on quality of life and in the development of candidate compounds
      undergoing clinical evaluation.

PMID- 17023913
TI  - Mediators and regulation of peristalsis.
AB  - Peristalsis is the main postprandial propulsive activity of the gut. It is
      mediated by neurons of the enteric nervous system, which form an integrated
      circuit composed of sensory neurons, modulatory interneurons, and motor neurons
      to the circular and longitudinal muscle layers. Work outlined in this review has
      identified, by anatomic, physiologic, and pharmacologic techniques, the myenteric
      neurons and neurotransmitters involved in the regulation of this reflex. Of
      particular note are studies identifying the role of 5-hydroxytryptamine4 (5-HT4)
      receptors in the initiation of the peristaltic reflex and the development of
      selective 5-HT4 agonists as potential therapeutic agents.

PMID- 17023914
TI  - Searching for intrinsic properties and functions of interstitial cells of Cajal.
AB  - Evidence is mounting that interstitial cells of Cajal may function as pacemaker
      cells and have a role in NO-mediated neurotransmission. Several colonic motor
      disorders may be associated with abnormal ICC function.

PMID- 17023915
TI  - Mucosal immunity.
AB  - Advances have been made in understanding specialized aspects of acquired mucosal
      immunity and the importance of cross-talk between host innate and acquired immune
      responses in host mucosal defense. These advances include elucidation of a
      molecular basis for the coordinated trafficking and retention of lymphocytes in
      intestinal sites, new insights into the possible extrathymic origin of mucosal T
      cells in the intestine, and the description of ligands that may be the targets of
      intraepithelial T-cell recognition. The past year has witnessed the
      characterization of an array of regulated epithelial cell mediators and responses
      important for host mucosal defense against enteric microbial pathogens and firmly
      establishes epithelial cells as an integral component of the mucosal immune
      network. Animal models continued to further understanding of intestinal
      inflammatory disease, and studies on tissue transglutaminase have generated
      significant new insights into the immunopathogenesis of human celiac disease.

PMID- 17023916
TI  - Current status of enteric vaccines.

PMID- 17023917
TI  - Bacterial infections of the small intestine and colon.
AB  - Enterotoxigenic Escherichia coli, Vibrio cholerae O1, Campylobacter jejuni,
      Salmonella species, and Shigella species are major causes of morbidity and death
      in diarrheal disease. More recently recognized pathogens are V. cholerae O139 and
      enterohemorrhagic E. coli. In addition to this, several presumptive virulence
      factors have been identified in diarrheagenic E. coli and in other species. To
      confirm these as virulence factors we need good diagnostic tools and good
      epidemiological studies. These are of vital importance to create vaccines for
      diarrheal diseases.

PMID- 17023918
TI  - Viral infections of the gastrointestinal tract.
AB  - Viral gastroenteritis is a major worldwide public health problem. The number of
      identified pathogens continues to increase, and characterization of the viral
      structures and functions must be inexorably pursued. Investigators have made
      considerable progress toward understanding the mechanisms of virus-cell
      interactions, host responses, and pathogenesis, but the application of this
      knowledge to improve disease treatment and prevention awaits further key
      discoveries. Despite deficiencies in knowledge of many aspects of these important
      issues, a vaccine for the most important pathogen, rotavirus, has been submitted
      to the US Food and Drug Administration for approval.

PMID- 17023919
TI  - Intestinal parasitic infections.
AB  - Our understanding of the biology of several intestinal parasites has progressed
      considerably in the past year, especially in the area of molecular biology.
      Information from molecular and genetic analyses has been used increasingly to
      improve understanding of pathogenesis, to apply improved diagnostic methods, and
      to seek new vaccination strategies. There were fewer relevant clinical studies
      than in previous years, but some are notable. Control of helminth infections by
      mass chemotherapy in school age children appears an achievable goal in many
      communities. Vaccine trials against some protozoan infections continue to show
      promise in animal models.

PMID- 17023920
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Intensive investigation into the interactions of Helicobacter pylori with the
      human host during the period of this review has led to several important
      developments in our understanding of H. pylori pathogenesis. There is direct
      evidence to support a central role for bacterial adhesion to host gastric
      epithelial Lewis antigens. Adherence can result in activation of host signaling
      cascades, including tyrosine phosphorylation events. H. pylori induces an immune
      response that is skewed toward a T-helper cell (Th) 1 phenotype, and an
      insufficient Th2 response is associated with the inability of the host to
      eradicate the organism. An area of active investigation has been the induction of
      epithelial apoptosis, both in direct response to H. pylori and by T-cell mediated
      pathways. Although the consensus is that the cagA gene product is not involved in
      pathogenesis, the presence of the cag pathogenicity island is associated with
      increased gastric inflammation and decreased epithelial repair. Interestingly,
      infection with cagA+H. pylori appears to result in decreased prevalence of both
      gastroesophageal reflux disease and adenocarcinoma of the esophagus and cardia.

PMID- 17023921
TI  - Treatment of Helicobacter pylori.
AB  - Overwhelming evidence implicates Helicobacter pylori as a significant causative
      factor in many gastroduodenal diseases. Effective multidrug antimicrobial
      regimens are available for cure of the infection, so investigative efforts are
      focusing on cost-effectiveness and treatment outcome in various populations.
      Potential associations between H. pylori and nongastric disorders are being
      examined. Recognition that infection is largely acquired during childhood has
      emphasized the need to study pediatric issues. Posttreatment studies confirm the
      importance of the bacterium in pathogenesis and relapse of peptic ulcer disease.
      Antimicrobial resistance has a negative impact on cure of the infection and
      healing of gastroduodenal lesions. Methodology to evaluate H. pylori
      antimicrobial susceptibility has been standardized by the National Committee for
      Clinical Laboratory Standards, and minimum inhibitory concentration breakpoints
      to standardize resistance assays are being established. Surveillance of H. pylori
      antimicrobial resistance is underway in a Centers for Disease Control and
      Prevention multisite project in the United States.

PMID- 17023922
TI  - Gastrointestinal infections in children.
AB  - Despite the important contribution of Helicobacter and Campylobacter infections
      to human disease, understanding of these organisms has lagged behind that of
      other enteropathogens. Developments in the molecular genetics of Helicobacter and
      Campylobacter species, however, undoubtedly will provide additional insights into
      the pathogenesis of infections caused by these related enteric pathogens.

PMID- 17023923
TI  - Gastrointestinal infections in the immunocompromised host.
AB  - Gastrointestinal infections are a frequent and important complication of
      immunodeficiency diseases and immunosuppressive therapy. Such infections may be
      severe, prolonged, or even fatal, whereas the same infections are typically mild
      and transient in immunocompetent persons. In this regard, the strong association
      between HIV-induced immunosuppression and the increased prevalence of severe
      enteric infections is strong evidence of the link between immune function and
      defense against enteric pathogens. Because gastrointestinal infections in
      immunocompromised persons are frequently severe and life-threatening, a vigorous
      approach to the diagnostic evaluation and therapeutic management is advocated by
      many clinical investigators. In this review, we summarize the important new
      developments, particularly during the past year, regarding gastrointestinal
      infections in immunocompromised persons.

PMID- 17023924
TI  - Treatment of gastrointestinal infections.
AB  - During the past year, we have seen the continuing spread of antimicrobial drug
      resistance in important gastrointestinal pathogens. Typhoid fever seen in the
      United States was multidrug resistant, but still susceptible to quinolones. The
      mechanism of quinolone resistant typhoid in Vietnam was better elucidated.
      Treatment failures in enterobacteriaceae treated with quinolones suggest that the
      minimum inhibitory concentration break point for resistance should be lowered.
      Evidence is mounting that ciprofloxacin and ofloxacin may be safely used to treat
      serious infections in children. Cefixime showed some promise in treating
      shigellosis in an open labeled trial. Decreased gastric acid secretion was
      associated with cholera but not dysentery. Phase 1 trials of vaccines for cholera
      and enterotoxigenic Escherichia coli showed promise. The antifungal drug,
      clotrimazole, demonstrated ability to inhibit secretory diarrhea in laboratory
      studies. Nitazoxanide demonstrated efficacy in both protozoan and helminthic
      infections in humans, including fascioliasis.

PMID- 17023925
TI  - Bibliography. Current world literature. Small intestine.

PMID- 17023926
TI  - Cyclooxygenase expression in intestinal epithelial cells.

PMID- 17023927
TI  - Impact of dietary fiber on absorption from the small intestine.

PMID- 17023928
TI  - Molecular and cellular biology of the small intestine.
AB  - The crypt-villus axis is composed of a dynamic cell population in perpetual
      change from a crypt proliferative and undifferentiated stage to a mature villus
      stage. The migration of crypt cells is accompanied by cellular differentiation
      that leads to morphological and functional changes. In addition to this intrinsic
      gene program, intestinal epithelial cells respond to extrinsic signals by
      producing various molecules. Using different experimental approaches, recent
      studies have further characterized intestinal epithelial-cell biology and
      provided evidence of their polyvalent and important role in gut homeostasis.

PMID- 17023929
TI  - Water and electrolyte absorption and secretion in the small intestine.
AB  - The use of gene-knockout mice permits an increased insight into the role of
      specific transport proteins and membrane receptors in epithelial water and
      electrolyte transport. Data on the secondary coupling of water transport to Na
      glucose cotransport and the mechanism of action of a number of prosecretory and
      proabsorptive enteric neurotransmitters are reviewed. Nitric oxide and some
      experimental treatments with therapeutic potential for cholera toxin-induced
      water and electrolyte secretion are discussed. A putative role of uroguanylin in
      intestinal bicarbonate secretion is explored.

PMID- 17023930
TI  - Nutrient absorption.
AB  - Interesting advances occurred recently in nutrient absorption. Kinetics of
      triacylglycerol appearance in endoplasmic reticulum, Golgi apparatus, and lymph
      support the hypothesis that endoplasmic reticulum-to-Golgi transport is rate
      limiting for lipid absorption. Apolipoprotein B does not appear necessary for
      initial formation of chylomicron-sized lipid particles in the endoplasmic
      reticulum, but rather for their movement out of the endoplasmic reticulum and to
      the Golgi. If peptides are protected from luminal proteolysis by fatty acylation,
      or if a nonpeptide drug, acyclovir, is esterified with valine to enhance
      bioavailability, the peptides nevertheless are absorbed by peptide transporters.
      Experimental conditions needed to use human ileal mucosa for in vitro absorption
      studies are described. Intestinal mucosa contains leptin receptors, and leptin
      inhibits galactose absorption, suggesting a new site for leptin's modulation of
      body mass. The enhancer element for the apoB gene is located much farther from
      its structural gene in the intestine than in the liver.

PMID- 17023931
TI  - Celiac disease.
AB  - There continues to be much research interest in celiac disease, with well over
      200 papers published in the year under review, covering a multitude of areas from
      population screening to the molecular immunology of disease pathogenesis. The
      high prevalence of "silent" disease again has been demonstrated, and there is
      continued emphasis on the increasingly wide recognized range of associated
      conditions and extraintestinal manifestations. The case for the safety of oats is
      further strengthened by a study involving patients with dermatitis hepetiformis.
      One of the most significant scientific advances has been the discovery of a
      potential role for tissue transglutaminase, recently found to be the autoantigen
      of antiendomysial antibodies, in disease pathogenesis, by enhancing gliadin
      peptide class II binding and consequent T-cell activation. However, the very
      central role of T cells has been thrown into doubt with an elegant study that
      assessed the effect of blocking costimulation in T-cell activation.

PMID- 17023932
TI  - Motility of the small intestine.
AB  - Motility of the small intestine is controlled by myogenic, neural, and hormonal
      mechanisms and is modulated by external influences such as meals, central nervous
      system activation, and immune factors. Small-bowel dysmotility is recognized in a
      number of diseases, but its precise role in symptom generation remains unclear in
      many instances. We review publications that in the year under review added to the
      basic understanding of small-intestinal motility as well as its alteration in
      disease.

PMID- 17023933
TI  - Diagnosis and management of small intestinal diseases.
AB  - Advances in the diagnosis and management of small bowel diseases are the subject
      of this review. Topics covered include improving the specificity of breath tests
      for bacterial overgrowth; small bowel enteroscopy; early diagnosis of mesenteric
      ischemia; the use of polymerase chain reaction for diagnosing central nervous
      system involvement in Whipple's disease; progress in defining the cause and
      pathogenesis of chronic idiopathic intestinal pseudoobstruction and the Peutz
      Jeghers syndrome; defining the role of gut barrier function in health and
      disease; the therapeutic role for bile acid-binding resins in diarrhea after
      refeeding in critically ill patients; use of genetic techniques and topical
      steroid therapy in treating graft-versus-host disease; and the beneficial effects
      of combination hormonal therapy in occult gastrointestinal blood loss resulting
      from angiodysplasia.

PMID- 17023934
TI  - Small intestinal pathology.
AB  - During the past year, important studies on various mechanisms of small bowel
      disease have been reported. The section on enterocyte function evaluates studies
      on hypoxia and apoptosis. Many of the studies of small intestinal epithelia use
      as models T84 cells. When these cells are referred to as intestinal cells, it may
      be in a general sense. This may be of relevance in permeability studies because
      the transepithelial resistance of T84 cells is on the order of 1000 to 2000
      ohm.cm, much higher than the resistance of the small intestine. These studies
      produce added insights into cellular function. Hypoxia causes changes in
      epithelial permeability through autocrine pathways. Additional studies
      methodically detail apoptosis in the small intestinal cell caused by ischemia
      reperfusion and the potential mechanisms. Apoptosis is also important in graft
      versus-host disease. A number of studies of the mechanism of action of
      Clostridium difficile toxins are reviewed; these may have therapeutic
      implications in the future. Finally, the role of mast cells in immunity and in
      postischemic inflammation is reviewed.

PMID- 17023935
TI  - Surgery of the small intestine.
AB  - This article reviews both clinical and scientific advances in surgery of the
      small intestine that have been reported in the last year. The management of both
      pediatric and adult intussusception is considered. Multiple studies on the
      evolving role of ileal pouch-anal anastomosis are assessed. The treatment and
      epidemiology of a wide variety of intestinal neoplasms are reviewed. Advances in
      small bowel transplantation are also reported. The cause of small bowel
      obstruction is considered as well as new strategies to prevent adhesion
      formation. Finally, a number of diverse topics relating to intestinal surgery,
      including new data on laparoscopic surgery, treatment of enterocutaneous
      fistulas, reconstruction after total gastrectomy, intestinal transit after
      ileocecal segment transposition, and ischemia/reperfusion and anastomotic
      healing, are reviewed.

PMID- 17023936
TI  - Refeeding the malnourished patient.

PMID- 17023937
TI  - Obesity: effects on the liver and gastrointestinal system.
AB  - Obesity, or the presence of a body mass index exceeding 30 kg/m, has assumed
      epidemic proportions in the United States. More than a cosmetic issue, obesity is
      associated with many comorbidities that contribute to multiple organ dysfunction,
      illness, and shortened life span. This review covers new and emerging information
      on the relationship of obesity to common and debilitating hepatic and
      gastrointestinal disorders, including nonalcoholic steatohepatitis,
      gastroesophageal reflux, gallstones, and increased risk of colon cancer.
      Understanding the role of obesity in these disorders should lead to new insights
      into the pathogenesis of common liver and gastrointestinal diseases and to new
      treatment strategies for the practicing gastroenterologist.

PMID- 17023938
TI  - Enteral nutrition in wasting disorders.
AB  - Cachexia, weight loss, and malnutrition are found commonly in patients with
      gastrointestinal tract cancer and in patients with human immunodeficiency virus.
      This wasting has been linked not only to survival, but also to alterations in
      host defenses, functional ability, and quality of life in these patients. Enteral
      nutritional support has been provided to these patients with the goal of
      preventing or correcting malnutrition in an attempt to improve measures of
      mortality, morbidity, and quality of life. Studies presented in this review have
      examined the impact of the timing, the composition, and the route of nutritional
      support on these outcome variables to evaluate the use of enteral nutritional
      support in these wasting disorders. There remains a paucity of strong clinical
      evidence that supports any improvements in outcome variables associated with the
      provision of enteral nutritional support in these patients.

PMID- 17023939
TI  - Parenteral nutrition.
AB  - The indications for parenteral nutrition have been examined over the past year.
      These studies have mostly supported the enteral compared to the intravenous
      route. Because a formal diagnosis of intestinal failure has not always been the
      key to initiating intravenous nutrition, however, the clinical applications of
      their conclusions are uncertain. Studies have also focused on supplementing
      intravenous nutrition with glutamine; the lack of ideal control groups makes
      interpretation difficult. Finally, based on present evidence, a pragmatic
      approach to the provision of intravenous nutrition can be supported.

PMID- 17023940
TI  - Intestinal absorption of vitamins.
AB  - This article provides an overview of advances in understanding the cellular and
      molecular mechanisms and regulation of intestinal absorption processes of
      vitamins. The vitamins covered are the water-soluble vitamins folic acid,
      cobalamin (vitamin B12), biotin, pantothenic acid, and thiamine (vitamin B1) and
      the lipid-soluble vitamin A. For folate, significant advances have been made in
      regard to i) digestion of dietary folate polyglutamates to folate monoglutamates
      by the cloning of the responsible enzyme; ii) identification of the cDNA
      responsible for the intestinal folate transporter; iii) delineation of
      intracellular mechanisms that regulate small intestinal folate uptake; and iv)
      identification and characterization of a specific, pH-dependent, carrier-mediated
      system for folate uptake at the luminal (apical) membrane of human colonocytes.
      Studies on cobalamine have focused on cellular and molecular characterization of
      the intrinsic factor and its receptor. Studies on biotin transport in the small
      intestine have shown that the uptake process is shared by another water-soluble
      vitamin, pantothenic acid. Furthermore, a Na-dependent, carrier-mediated biotin
      uptake system that is also shared with pantothenic acid has been identified at
      the apical membrane of human colonocytes. This carrier is believed to be
      responsible for the absorption of the bacterially synthesized biotin and
      pantothenic acid in the large intestine. Also, preliminary studies have reported
      the cloning of a biotin transporter from the small intestine. As for thiamine
      intestinal transport, a study has shown thiamine uptake by small intestinal
      biopsy specimens to be via a carrier-mediated, Na-independent mechanism, which
      appears to be up-regulated in thiamine deficiency. Studies on vitamin A
      intestinal absorption have shown the existence of a receptor-mediated mechanism
      for the uptake of retinol bound to retinol-binding protein in the small intestine
      of suckling rats. Another study has shown that retinoic acid increases the mRNA
      level of the cellular retinol binding protein II and the rate of retinol uptake
      by Caco-2 intestinal epithelial cells. The study suggested that retinoids may
      play a role in the regulation of vitamin A intestinal absorption.

PMID- 17023941
TI  - Nutrition and cancer: the herbal revolution.
AB  - There is growing evidence that compounds of plant origin have the ability to
      prevent cancer. Populations with greater reliance on fruits and vegetables in the
      diet experience a reduced risk for the major cancers. Research has focused on
      specific micronutrients and nonnutrient compounds that may have health benefits.
      The term phytochemical means any compound of plant origin. This review focuses on
      the cancer-preventive aspects of phytochemicals and their mechanisms of action.
      The term phytomedicine applies to the health-maintaining aspects of these
      compounds and their implications for raising the standard of public health.

PMID- 17023942
TI  - Bibliography. Current world literature. Liver.

PMID- 17023943
TI  - Hepatology.

PMID- 17023944
TI  - Cellular and molecular biology of the liver.
AB  - This paper highlights several key issues, ideas, and findings that significantly
      contribute to our understanding of the organization, communication, and molecular
      machinery of the liver. The functional anatomy of the liver has been studied in
      several ways that have revealed the extent of the biliary tree within the hepatic
      parenchyma, including identification of the canals of Hering as their most distal
      ramification. The canals of Hering are also considered as the potential residence
      of hepatic progenitor cells. Hepatocytes can "communicate" with each other via
      gap junctions, but might also deliver hormones and nucleotides downstream to
      cholangiocytes. The interaction of inflammatory cells and inflammatory mediators
      with hepatocytes is of particular importance in transplant immunology, infection,
      inflammation, viral hepatitis, and fibrogenesis. The role of these mediators as
      well as certain "toxic" bile acids in apoptosis has become clearer with the
      discovery of the mitochondrial permeability transition. Moreover, ursodeoxycholic
      acid can reduce apoptosis by minimizing the mitochondrial permeability
      transition. Two new nuclear hormone receptors, PXR and SXR, have been identified.
      These are both activated by a variety of chemically distinct ligands, whose final
      common goal is the activation of cytochrome P450-containing drug-metabolizing
      enzymes. Thus, these two receptors are critical to the body's ability to
      metabolize a variety of compounds properly. Additional insight into the role of
      cytokines and cytokine receptors in liver regeneration is presented. Finally, in
      vivo gene therapy of liver-expressed genes by chimeric oligonucleotides appears
      quite promising as a means of correcting single nucleotide gene defects.

PMID- 17023945
TI  - Pathology of the liver.
AB  - Among the topics of recent investigation in liver pathology were an examination
      of normal portal tract structures in needle liver biopsies, computer
      reconstructions of the intrahepatic biliary tree, identification of oval cells
      (presumed progeny of hepatic stem cells) in a variety of biliary and nonbiliary
      diseases and tumors, the features and pathogenesis of nonalcoholic
      steatohepatitis, and further characterization of proliferating bile ductules. A
      morphometric study of portal structures in normal needle liver biopsies found
      that approximately one third in a given specimen may not show a portal vein and
      that a bile duct may not be seen in 7%. Apoptosis is a critical mechanism for the
      death of hepatocytes in viral hepatitis and also in endothelial injury in the
      cold perfusion-warm reperfusion sequence in liver transplantation. The results of
      two studies examining the relationship of steatosis to chronic hepatitis C virus
      infection in native and transplanted livers suggest that fatty change is a
      specific virus-mediated lesion. In the field of hepatic neoplasia, liver cell
      dysplasia (large cell change), long thought to be a premalignant lesion, was
      hypothesized to represent abnormal hepatocyte polyploidization.

PMID- 17023946
TI  - Inherited metabolic disease.
AB  - Our understanding of the pathophysiology and of new treatments for inherited
      metabolic diseases that affect the liver continues to grow through the study of
      gene mutations and their functional effect on the proteins they encode. For
      genetic hemochromatosis and Wilson's disease, studies focused on the function of
      their respective gene products provide new insights into metal metabolism. For
      Crigler-Najjar syndrome, an inherited disorder that results in failure of proper
      bilirubin glucuronidation, the once futuristic idea of treatment by
      transplantation of donor hepatocytes has now proven successful in a human
      recipient. With continued study and experimentation, our diagnostic and
      therapeutic capabilities will continue to expand for these and other inherited
      metabolic disorders. Although this increase in new information has sparked
      numerous reviews of these subjects, the following are highlights from the past
      year that include information relative to disease diagnosis and treatment, as
      well as new insights into pathogenesis.

PMID- 17023947
TI  - Drug-induced liver disease.
AB  - The past year has seen several additions to the list of drugs that cause hepatic
      injury. Many of these agents produce fulminant hepatic necrosis and, in some
      cases, were withdrawn from the market (eg, bromfenac). Other drugs had warnings
      placed in their labeling along with stringent monitoring guidelines to alert
      physicians and patients alike to the potential for severe hepatic injury (eg,
      troglitazone, tolcapone). New reports of hepatoxicity continued to appear for
      many older agents, in some cases expanding the hepatotoxic spectrum for the
      drugs. Vanishing bile duct syndrome has drawn increasing attention and is now
      associated with more than 30 drugs. Ibuprofen is among those drugs newly
      described as causing this syndrome. Hepatitis C virus infection was reported as a
      possible risk factor for ibuprofen hepatotoxicity, raising the issue of safe use
      of nonprescription as well as prescription drugs in patients with underlying
      liver disease. Reports have appeared about acetaminophen-induced hepatotoxicity
      in several dozen children from unintentional overdoses, in addition to cases of
      therapeutic misadventure in adults.

PMID- 17023948
TI  - Cholestatic syndromes.
AB  - Recent advances in cholestatic liver disease have occurred in several areas.
      Molecular cloning of hepatobiliary transport systems has resulted in the
      identification of the molecular basis of hereditary and acquired cholestatic
      syndromes. Apoptosis has been identified as an important mechanism of cholestatic
      liver injury and bile duct loss. New insights into the pathogenesis of pruritus
      and fatigue have resulted in new treatment strategies for these debilitating
      symptoms. Important new studies have been published about pathogenesis, clinical
      features, and treatment of primary biliary cirrhosis, primary sclerosing
      cholangitis, cholestasis of pregnancy, and drug-induced cholestasis.

PMID- 17023949
TI  - Hepatobiliary infections.
AB  - Major hepatobiliary infections include cholangitis and liver abscess. Liver
      abscess is typically either of pyogenic or amebic origin. Amebic liver abscess
      usually occurs in individuals from endemic areas or those traveling to endemic
      areas and is associated with an excellent prognosis if properly managed, usually
      with one of several antiamebicidal drugs alone. Pyogenic liver abscess is most
      often cryptogenic in origin, although sophisticated advanced interventional
      procedures such as transarterial embolization and cryoablation are leading to a
      new generation of patients with pyogenic liver abscess. A distinct clinical
      entity appears to be evolving, namely that of monomicrobial Klebsiella pneumoniae
      pyogenic liver abscess, characterized by the same symptoms and signs as classic
      pyogenic liver abscess, but further distinguished by the presence of diabetes
      mellitus, a paucity of coexistent intra-abdominal pathology, a single cavity, and
      an excellent prognosis. As of 1999, the vast majority of pyogenic liver abscesses
      should be approached therapeutically by percutaneous aspiration or drainage
      techniques. The overall prognosis for patients with pyogenic liver abscess is
      improving, although poor outcomes are common in patients with serious underlying
      medical disorders, especially malignancy.

PMID- 17023950
TI  - Viral hepatitis.
AB  - Viral hepatitis is still one of the most common causes of acute and chronic liver
      disease worldwide. Major advances have been made in our knowledge of these
      diseases, many during the past year. Molecular biology and clinical studies have
      improved our understanding of the mechanisms of antiviral drugs, as well as viral
      resistance to therapy. The risks of hepatitis A in patients with chronic liver
      disease have been confirmed, and the efficacy of hepatitis A vaccines in these
      patients has been proven. Aggressive combination therapy has emerged as a
      promising strategy for chronic hepatitis B and C, and techniques for immune
      prophylaxis for hepatitis B are being improved. Liver transplantation has become
      routine for end-stage hepatitis B virus liver disease, and new strategies to
      prevent and treat recurrence are being explored. This review discusses the recent
      advances in our knowledge of hepatitis viruses A through G, focusing on the
      literature of the past year.

PMID- 17023951
TI  - Autoimmune liver disease.
AB  - The incidence and prevalence of autoimmune hepatitis are greater than expected
      among white northern Europeans. Patients with type 2 autoimmune hepatitis have
      different HLA frequencies than patients with type 1 disease and HLA-DRB1*07 may
      be an important risk factor. Hepatitis C virus can trigger autoimmune hepatitis
      after needlestick inoculation. Elderly patients have milder disease than young
      patients and they are frequently untreated. Cryptogenic chronic hepatitis is
      indistinguishable from autoimmune hepatitis and it responds as well to
      corticosteroids. Variant syndromes are common and the degree of cholestasis
      influences the treatment response. Endomysial antibodies indicate celiac sprue in
      asymptomatic patients, and multiple endocrinopathies in individuals with type 2
      disease may reflect molecular mimicries and cross-reacting autoantibodies. Phase
      I (cytochromes P-450) and phase II (uridine diphosphate glucuronosyltransferases)
      drug-metabolizing enzymes are the autoantigens of syndromes characterized by
      liver/kidney microsomal autoantibodies. T-cell vaccination prevents the
      occurrence of experimental hepatitis in mice and it can also treat the disease.
      Liver transplantation can be complicated by recurrent disease, frequent allograft
      rejection, and de novo autoimmune hepatitis.

PMID- 17023952
TI  - Pediatric liver disease.
AB  - Pediatric hepatology has advanced greatly over the past few years. Many more
      children with severe liver disease are now surviving into adulthood. There is a
      number of conditions not seen in adult practice that have been the focus of
      research efforts, and many of these efforts have borne fruit in the past year.
      Disorders characterized by intrahepatic cholestasis in particular have now been
      substantially unravelled, and this work has elucidated a great deal about hepatic
      physiology. Liver-directed gene therapy is on the threshold of human application.
      This research has been facilitated by excellent animal models and the advent of
      isolated hepatocyte transplantation. Relatively common conditions such as biliary
      atresia, however, remain largely unexplained and the viral hepatitides have no
      effective form of treatment. It remains a hope that our increase in knowledge in
      the fields of genetics and immunology will translate into advances in therapy.

PMID- 17023953
TI  - Hepatocellular carcinoma.
AB  - Hepatitis C infection is associated with the development of hepatocellular
      carcinoma, and progress has been made in a number of areas. Transgenic mice lines
      expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and
      hepatocellular carcinomas, with no significant hepatitis or fibrosis. This
      implies that hepatitis C can lead directly to malignant transformation. A new
      lesion, irregular regeneration, has been described in chronic hepatitis C
      infection and is associated with a 15-fold increase in the relative risk of
      developing hepatocellular carcinoma. A minority of patients with hepatitis C
      related hepatocellular carcinoma have intense lymphocytic infiltration of the
      cancer, a feature associated with a better prognosis. Several studies have
      confirmed the association between large cell dysplasia and hepatocellular
      carcinoma. However, large cell dysplasia may not be a premalignant lesion and
      instead may be a marker for premalignant alterations elsewhere in the liver. Oral
      contraceptives previously have been linked to an increased risk of hepatocellular
      carcinoma. A large multicenter European case-control study has shown minimal
      increased risk of hepatocellular carcinoma with use of steroidal contraception.
      Tamoxifen had shown promise in the management of advanced hepatocellular
      carcinoma. However, a randomized placebo-controlled study of 477 patients with
      hepatocellular carcinoma found no benefit from tamoxifen. In a preliminary study,
      however, octreotide has shown improved survival and quality of life in patients
      with advanced hepatocellular carcinoma. Finally, interferon treatment continues
      to be linked to a reduced risk of hepatocellular carcinoma in patients with
      hepatitis C. These studies generally are not randomized, and a randomized
      prospective study is required to address this issue.

PMID- 17023954
TI  - Portal hypertension.
AB  - Cirrhosis represents the end stage of any chronic liver disease. Two major
      syndromes result from cirrhosis: portal hypertension and hepatic insufficiency.
      Additionally, vasodilatation and the hyperdynamic circulation are hemodynamic
      abnormalities typical of cirrhosis and portal hypertension. Complications of
      cirrhosis occur as a consequence of a combination of these factors.
      Gastroesophageal varices result almost solely from portal hypertension, although
      the hyperdynamic circulation contributes to variceal growth and hemorrhage.
      Ascites results from sinusoidal hypertension and sodium retention, which is, in
      turn, secondary to vasodilatation and activation of neurohumoral systems.
      Hyponatremia and the hepatorenal syndrome result from water retention and renal
      vasoconstriction, respectively, both of which are also consequences of peripheral
      vasodilatation. Vasodilatation that occurs in the pulmonary circulation leads to
      the hepatopulmonary syndrome. Another complication of cirrhosis, portosystemic
      encephalopathy, is a consequence of both portal hypertension (shunting of blood
      through portosystemic collaterals) and hepatic insufficiency. This paper reviews
      the recent advances in the pathophysiology and management of the complications of
      cirrhosis and portal hypertension.

PMID- 17023955
TI  - Acute liver failure.
AB  - Severe hepatitis A infection is an infrequent but well-recognized cause of acute
      liver failure that can now be effectively prevented with vaccination against
      hepatitis A virus. Bromfenac and troglitazone hepatotoxicity as well as various
      herbal remedies are some of the newly identified causes of acute liver failure.
      The recently identified transfusion-transmitted virus has been implicated in some
      cases of idiopathic acute liver failure whereas hepatitis G virus does not appear
      to be a causative agent. Recognizing, monitoring, and treating patients with life
      threatening cerebral edema remain critically important but difficult aspects of
      the clinical care of acute liver failure. Hypothermia and N-acetylcysteine are
      promising experimental approaches to cerebral edema but emergency liver
      transplantation is the only proven means of improving patient survival. Although
      recent changes in organ allocation may reduce waiting time to transplantation,
      more reliable and validated markers of liver regeneration and prognosis are
      needed to triage patients. The potential application and limitations of novel
      technologies including bioartificial liver devices and auxiliary liver
      transplantation continue to evolve from pioneering work in animal models and
      human subjects.

PMID- 17023957
TI  - Bibliography current world literature.

PMID- 17023956
TI  - Liver transplantation.
AB  - The growing disparity between available organs for liver transplantation and the
      number of waiting recipients has prompted significant debate over organ
      allocation and distribution. In light of this debate, recipient selection and
      prediction of factors relating to outcome have become increasingly important.
      Current immunosuppressive regimens provide excellent short-and long-term survival
      for patients and grafts. Increasingly, efforts are being made to decrease or
      withdraw immunosuppression late after transplantation to minimize long-term side
      effects. Viral disease, particularly cytomegalovirus infection, results in
      significant morbidity and mortality in patients. However, strategies for
      targeting high-risk patients with prophylactic antiviral therapy have been
      successful in reducing the incidence of cytomegalovirus disease. Recurrent viral
      hepatitis following liver transplantation may limit long-term graft success.
      Lamivudine appears to limit recurrent infection with hepatitis B virus in a
      significant number of patients who develop this condition following liver
      transplantation and may represent a cost savings over hepatitis B immunoglobulin.
      Although the overall survival of patients with chronic hepatitis C virus
      infection after orthotopic liver transplantation is excellent, significant
      morbidity and mortality occur in the subset of patients with severe recurrent
      disease. Interferon may delay the onset of disease in patients infected with
      hepatitis C virus following orthotopic liver transplantation, and investigation
      continues into antiviral therapy in this group of patients.

PMID- 17023958
TI  - Inflammatory bowel disease 1999: present and future promises.

PMID- 17023959
TI  - Lessons for human inflammatory bowel disease from experimental models.
AB  - Experiments carried out in new rodent models of chronic intestinal inflammation
      provide important clues about the pathogenesis of human inflammatory bowel
      disease (IBD). Genetic factors and enteric microflora are driving forces
      regulating mucosal immune responses, some of which are pathogenic and lead to
      colitis. CD4(+) T cells are the major pathogenic cells in colitis, and the type
      of injury depends on the nature of the cytokine imbalance. The cytokine network
      controlled by CD4(+) T cells dictates the outcome of the mucosal immune
      responses. Certain cytokines, such as transforming growth factor-beta and
      interleukin-10, have a suppressive role, and immunoregulatory T cells capable of
      secreting these cytokines may be induced at intestinal mucosal sites. Lessons
      learned from these experimental models are leading to new strategies for the
      treatment of IBD.

PMID- 17023960
TI  - Pathogenesis of inflammatory bowel disease.
AB  - In spite of expanding knowledge of cellular and molecular mechanisms of
      intestinal inflammation, the etiology and pathogenesis of inflammatory bowel
      disease (IBD) remain obscure. The link between the environment and IBD is still
      circumstantial, but definite progress is occurring in defining genetic
      susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The
      notion that normal enteric flora play a role in initiating or maintaining IBD is
      gaining momentum. Some components of the flora may act as noxious agents, whereas
      others (probiotics) seem to have a protective effect. The importance of the
      mucosal immune system to IBD is established, and evidence is accumulating that
      nonimmune components, such as epithelial, mesenchymal, and endothelial cells,
      also contribute to gut inflammation. The effect of cytokines in intestinal
      immunity is being elucidated by studies on their molecular mechanism,
      particularly the activation of nuclear factor (NF)-kappaB. Finally, the
      beneficial effects of cytoprotective prostaglandins and cell adhesion molecule
      (CAM) blockade promise novel therapeutic opportunities derived from an improved
      understanding of IBD pathogenesis.

PMID- 17023961
TI  - Treatment of ulcerative colitis.
AB  - Advances in the treatment of ulcerative colitis have continued to focus on
      improved local delivery of existing agents, such as 5-aminosalicylate and
      corticosteroids, and on novel immunosuppressive agents. Although newer
      preparations of 5-aminosalicylate continue to provide incremental benefits in
      safety, tolerance, and efficacy, there is a growing understanding of the limits
      of benefit from increasing doses. Knowledge of the safety of these agents,
      particularly in regard to their use in pregnancy, continues to expand. Novel
      corticosteroids are used in much of the world for the treatment of ulcerative
      colitis, with the exception of the United States, with anticipated benefits in
      safety but little additional therapeutic benefit. Innovative use of oral emulsion
      preparations of cyclosporine has been reported in the treatment of ulcerative
      colitis and adds to the growing body of literature on the efficacy of
      cyclosporine in severe disease. Relatively limited experience with other
      immunosuppressive agents, such as tacrolimus, has been reported. The role of
      antibiotics in the treatment of ulcerative colitis has continued to present
      controversy.

PMID- 17023962
TI  - Cytokine-based therapies in inflammatory bowel disease.
AB  - Cytokine-based therapy for inflammatory bowel disease (IBD) has significantly
      advanced in the last year. This review highlights some of the exciting progress
      that has occurred. The efficacy of anti-tumor necrosis factor (TNF) monoclonal
      antibody therapy in Crohn's disease has promoted further research and the
      development of other anti-TNF therapies, such as thalidomide, phosphodiesterase
      type IV inhibitors, and new-generation anti-TNF monoclonal antibodies. Current
      research is also focused on more proximal events in the inflammatory cascade to
      modify T-cell regulation and to decrease the production and activity of
      proinflammatory proteins, cytokines, and nuclear regulatory factors.
      Concurrently, the emerging role of interleukin (IL)-11, IL-12, and IL-18 in the
      perpetuation of chronic inflammation continues to stimulate much interest. All of
      these new advancements reveal an exciting future for IBD therapy.

PMID- 17023963
TI  - Medical therapy for Crohn's disease.
AB  - The past year's literature pertaining to the medical treatment of Crohn's disease
      was highlighted by the US Food and Drug Administration's approval of infliximab.
      Other developments of interest include more evolutionary (in contrast to
      revolutionary) clinical data regarding aminosalicylates, antibiotics, and
      steroids as inductive agents and use of immunomodulatory agents as maintenance
      therapies. Comparative trials continue to demonstrate that steroids, including
      budesonide, have a greater acute benefit than aminosalicylates, but this benefit
      does not translate into long-term efficacy. Azathioprine and 6-mercaptopurine are
      the standard maintenance therapies for steroid-dependent Crohn's disease, and
      long-term safety data continue to accumulate regarding these agents in adults and
      children. Several novel approaches have been reported in preliminary fashion that
      will require much more extensive clinical experience and controlled-trial
      evidence.

PMID- 17023964
TI  - Genetics and inflammatory bowel disease.
AB  - Genetic factors have a definite role in the etiology of inflammatory bowel
      disease (IBD). The mode of inheritance suggests a polygenic disease with the
      penetrance of the genetic factors being strongly influenced by the lifestyle of
      an industrialized society. Molecular techniques, which have become available
      through the progress of the human genome project, allowed a first series of
      linkage studies in pairs of affected siblings with IBD, which suggested multiple
      genomic susceptibility regions. These regions are still large, but considerable
      progress is being made toward the identification of actual disease genes. It is
      hoped that an understanding of the genetic etiology of IBD will lead to enhanced
      diagnostic procedures, more effective therapeutic interventions, and preventive
      strategies in the future.

PMID- 17023965
TI  - Inflammatory bowel disease in pediatric patients.
AB  - The management of inflammatory bowel disease in children remains a major
      challenge to patients, their families, and the health care team. This review
      highlights the past year's advances concerning epidemiologic studies, new
      diagnostic considerations, and novel therapeutic approaches. Epidemiologic
      studies confirmed that Crohn's disease is being increasingly diagnosed in
      children, whereas the incidence of ulcerative colitis has remained stable.
      African-American children are as likely to have inflammatory bowel disease as
      other children. Serologic assays specific for Crohn's disease and ulcerative
      colitis can assist clinicians in screening for inflammatory bowel disease, as
      well as discriminating between the two diseases. Studies have revealed that
      osteopenia and antioxidant vitamin deficiency are common and require screening in
      pediatric inflammatory bowel disease. Increasing experience with
      immunosuppressive drugs (6-mercaptopurine, azathioprine) point to their efficacy
      and generally good toxicity profile in pediatric patients.

PMID- 17023966
TI  - Surgical treatment of inflammatory bowel disease.
AB  - Although laparotomy with resection remains the treatment of choice for most
      patients who require surgery for intestinal Crohn's disease, mounting evidence
      supports the safety and efficacy of less traditional approaches and procedures
      (ie, laparoscopy, stricture-plasty). In contrast to the approach to intestinal
      disease, many centers are advocating a more aggressive operative approach to
      perianal Crohn's disease. Over the past few years, restorative proctocolectomy
      with ileal pouch-anal anastomosis has emerged as the operation of choice for most
      patients requiring surgery for ulcerative colitis. As experience with the
      operation grows, patient selection, technical features, and management of
      postoperative complications are being more clearly defined and optimized.

PMID- 17023967
TI  - Esophagology.

PMID- 17023968
TI  - Gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is a common clinical problem. Transient lower
      esophageal sphincter relaxation is central to the pathogenesis. New studies have
      identified the importance of nitric oxide and cholinergic pathways in modulating
      transient lower esophageal sphincter relaxation. Provocative information suggests
      that infection with Helicobacter pylori may protect patients from developing
      complications of gastroesophageal reflux disease. Endoscopy may be used by
      clinicians to tailor therapy, but an empiric trial of a proton pump inhibitor may
      be an alternative diagnostic approach. Nocturnal acid breakthrough during proton
      pump inhibitor therapy has emerged as an important new treatment concept,
      although its clinical importance remains unproven. Studies continue to show that
      laparoscopic antireflux surgery is a cost-effective treatment option for patients
      requiring maintenance therapy with proton pump inhibitors. However, the minimally
      invasive nature of the operation should not alter the indications for antireflux
      surgery, especially for patients with atypical symptoms.

PMID- 17023969
TI  - Esophageal motor disorders.
AB  - A consolidation of ideas regarding the pathogenesis and management of esophageal
      motor disorders occurred over the past year. The development and application of
      diagnostic techniques has stimulated new thinking about the events responsible
      for peristalsis and has provided novel avenues for studying mechanisms of symptom
      production. Achalasia remains the most investigated and understood motor
      disorder, and the year's research focused heavily on management approaches for
      this important condition. Other topics addressed in this review include proximal
      esophageal symptoms and disorders, spastic disorders, and esophageal
      hypomotility.

PMID- 17023970
TI  - Chest pain of esophageal origin.
AB  - The treatment of patients with unexplained chest pain is difficult and
      challenging. After a cardiac etiology has been ruled out, a diligent search for
      an esophageal etiology-gastroesophageal reflux disease, motility abnormalities,
      or esophageal hypersensitivity-should be undertaken with judicious use of a
      diagnostic (therapeutic) trial of therapy, ambulatory pH monitoring, or
      esophageal manometry. The recent literature discusses the use of high-dose
      omeprazole in diagnosing and treating chest pain associated with gastroesophageal
      reflux disease, correlates abnormal ambulatory pH monitoring with response to
      omeprazole, and provides additional insights into the pathogenesis of esophageal
      chest pain.

PMID- 17023971
TI  - Barrett's esophagus.
AB  - Intestinal metaplasia in Barrett's esophagus is a major risk factor for
      esophageal adenocarcinoma, a tumor whose incidence rate has more than tripled in
      the United States over the past 2 decades. Studies have identified a number of
      molecular abnormalities that may be involved in the progression from dysplasia to
      cancer in Barrett's esophagus, including altered expression of cadherins and
      catenins; inactivation of tumor-suppressor genes, such as p53, p21, p27, and p16;
      and increased activity of the enzymes cyclooxygenase-2 and inducible nitric oxide
      synthase. Studies on the role of Helicobacter pylori in the pathogenesis of
      intestinal metaplasia at the gastroesophageal junction have yielded contradictory
      results. It appears, however, that gastric infection with strains of H. pylori
      containing a cagA gene associated with cytotoxin expression may protect against
      the development of dysplasia and adenocarcinoma in Barrett's esophagus. The role
      of ablation therapy for Barrett's esophagus remains controversial, largely
      because thermal and photochemical ablative techniques often leave foci of
      intestinal metaplasia behind.

PMID- 17023972
TI  - Endoscopic therapeutic esophageal interventions.
AB  - Cyanoacrylat and fibrin glue seem to be no better alternatives to ligation in the
      treatment of bleeding esophageal varices. Studies with photodynamic therapy (PDT)
      of high-grade dysplasia (HGD) and early esophageal cancer show encouraging
      results. The use of 5-aminolaevulinic acid (ALA) as a photosensitizer minimizes
      the rate of severe side effects, but only in HGD and tumors with a depth of 2 mm
      or less can a complete remission be achieved. The use of Lugol's iodine solution
      is sensible for the detection of HGD and early squamous cell cancers. Thermal
      ablation with Neodym:YAG laser and self-expanding metal stents are the most
      important modalities for palliative treatment of esophageal cancer.

PMID- 17023973
TI  - Esophageal cancer.
AB  - Carcinoma of the esophagus and gastroesophageal junction continues to be an
      aggressive cancer with poor prognosis, despite improved surgical results and the
      potential benefit of combined multimodality regimens. Additional data seem to
      confirm the rising incidence of adenocarcinoma, although users of nonsteroidal
      anti-inflammatory drugs seem to have a decreased risk. Much attention is focused
      on detecting high-grade dysplasia and early carcinoma with promising results
      using red fluorescence after preceding 5-aminolevulinic acid (ALA) sensitization.
      Positron emission tomography made a major breakthrough and seems to be superior
      to computed tomography in detecting distant metastasis as well as lymph node
      metastasis. Endoscopic ablation of early carcinoma results in promising early
      results, but a major issue remains the EUS discrimination between Tis-T1a and
      T1b, as the latter is frequently associated with lymph node metastasis. In the
      field of molecular biology, research is unraveling the role of cadherins and
      catenins in the mechanism underlying cell adherence, cell movement, and progress
      toward tumor formation. Mutations of p53 are correlated with loss of apoptosis
      and form an early step in progress toward carcinoma as well as mutations of other
      tumor-suppressing genes (eg, p16 and Rb mutations). Detection of such mutations
      may become useful prognostic indicators, but illustrate the genetic polymorphism
      influencing the susceptibility to carcinoma. Several lines of evidence suggest
      that the stabilizing or overriding of p53 mutant cancer cells and restoration of
      the wild-type tumor suppressor gene p53 may improve results of DNA damaging
      treatment modalities. Further research in this field may lead to new forms of
      anticancer therapy.

PMID- 17023975
TI  - Bibliography current world literature.

PMID- 17023974
TI  - Surgery, radiotherapy, and chemotherapy for esophageal cancer.
AB  - Operative resection, the standard of care in the radical management of
      locoregional esophageal cancer, is a major surgical procedure, with a clear
      learning curve. It should be performed by experienced surgeons with a sufficient
      annual volume of procedures to maintain competence. Within specialized units
      esophagectomy can be safely offered to appropriately selected patients of all age
      groups. So far, the choice of operative approach (transhiatal, limited
      transthoracic, extended transthoracic) still cannot be based on randomized data
      with sufficient discriminating power. To date, the role of preoperative
      neoadjuvant therapy has not been clearly defined. A meta-analysis of five
      randomized trials did not confirm a substantial benefit for preoperative
      radiotherapy. A large randomized trial failed to show any benefit for
      preoperative chemotherapy. Improving systemic therapy, probably in combination
      with radiotherapy, remains a high priority for the coming years. The recent
      identification of new, highly active, chemotherapeutic agents shows promising,
      albeit preliminary, results.

PMID- 17023977
TI  - Neurohumoral control of the exocrine pancreas.
AB  - Recent advances in the study of pancreatic exocrine secretion are reviewed, with
      an emphasis on neurohumoral mechanisms. In the past year, cDNA for the human
      pancreatic sodium-bicarbonate cotransporter was cloned, and the expressed protein
      was localized to pancreatic acini and ductal cells. Recent information suggests
      that the cholecystokinin B receptor has a role in pancreatic amylase release.
      Further evidence supports the concept of a protease-sensitive negative feedback
      mechanism regulating pancreatic exocrine secretion. Study of the expression of
      the receptors responsible for the regulation of pancreatic function has proven
      fruitful in the determination of the molecular mechanisms of hormone signal
      transduction and desensitization. Studies of peptide 1, pituitary adenylate
      cyclase-activating peptide, and gastrin-releasing peptide have shown how these
      peptides participate in the regulation of pancreatic secretion and have provided
      information on intracellular signaling pathways obtained using rat pancreatic
      tumor cells. Neural regulation via cholinergic receptors in isolated pancreatic
      acini and the mechanisms responsible for other neurotransmitters, such as
      calcitonin gene-related peptide, histamine, and dopamine, are reviewed. This
      review highlights recent discoveries in the neurohumoral regulation of pancreatic
      exocrine secretion.

PMID- 17023978
TI  - Intracellular regulatory mechanisms in pancreatic acinar cellular function.
AB  - The intracellular mechanisms regulating pancreatic acinar cell function are more
      complex than previously realized. This is probably due in part to the need to
      match the biosynthetic and secretory functions of the cells. Much information is
      available on how secretagogue receptors acutely couple through heterotrimeric G
      proteins to increase intracellular messengers, particularly cytoplasmic free
      Ca(2+), although details are still being worked out. Less is known about how
      Ca(2+) signals to induce fusion of zymogen granules with the apical plasma
      membrane. Investigation has focused on the proteins of the zymogen granule
      membrane, and several novel proteins have recently been identified. In addition,
      understanding of the three MAP kinase cascades, the mTOR-p70S6 kinase pathway,
      and the focal adhesion kinase pathway in acinar cells is increasing. The
      functions of these pathways in acini have been linked to mitogenesis, protein
      synthesis, and regulation of the cytoskeleton.

PMID- 17023979
TI  - Acute pancreatitis.
AB  - Efforts to unravel the intracellular processes that occur in acute pancreatitis
      continue. In cerulein pancreatitis, new evidence supports the idea that a very
      early event is premature trypsinogen activation triggered by lysosomal cathepsin
      B. Clinicians persist in trying to identify more sensitive and specific
      prognostic signs of the severity of attacks of pancreatitis; one study suggests
      that computer-based neural networks may be an alternative to biochemical markers
      and clinical scoring systems. The systemic severity of episodes of pancreatitis
      seems to be related to a multitude of proinflammatory cytokines and chemokines
      acting at sites distant from the pancreas. Selective blockade of some of these
      peptides (eg, endothelin-1 and platelet-activating factor) has decreased
      mortality and distant organ damage in animal models and may deserve clinical
      evaluation. Gene therapy may be more efficient than pharmacologic therapy in
      increasing anti-inflammatory cytokine (interleukin-10) levels. Clinical studies
      have further underlined the usefulness of prophylactic antibiotics in severe
      acute pancreatitis. Radiologic and endoscopic techniques may be alternatives to
      surgery for certain complications of pancreatitis (eg, infected necrosis and
      pseudocysts) in particular subsets of patients.

PMID- 17023980
TI  - Chronic pancreatitis.
AB  - In the past year, numerous important papers were published on chronic
      pancreatitis, its causes, and its diagnosis; the cause of fibrosis; and pain in
      pancreatic cancer. More than 750 mutations have been described in the cystic
      fibrosis transmembrane regulator (CFTR) gene. Some mutations cause relatively
      mild reductions in CFTR function and may lead to disease in one organ without
      clinical involvement of other organs. Two groups of investigators recently
      reported that "idiopathic" chronic pancreatitis may be the sole manifestation of
      some CFTR mutations. Some recent reports may enhance our understanding of
      pancreatic fibrogenesis and may lead to therapies for painful chronic
      pancreatitis. Pancreatic stellate cells are vitamin A-containing cells that
      resemble hepatic stellate cells and were recently isolated from rat and human
      pancreas. They respond to inflammatory cytokines by producing collagen. Two
      studies show that endoscopic ultrasonography (EUS) correlates well with
      endoscopic retrograde cholangiopancreatography in moderate to severe chronic
      pancreatitis. However, in patients who have a few nondiagnostic abnormalities on
      EUS, these results have poor correlation with the results of endoscopic
      retrograde cholangiopancreatography and the secretin test. The clinical
      significance of these abnormalities is unclear, and the diagnosis of chronic
      pancreatitis should not be based on EUS findings alone. Painful chronic
      pancreatitis is a complex and difficult management problem. A recent study of
      alcoholic chronic pancreatitis suggests that the best predictors of pain relief
      are an intermittent pattern of pain and the presence of surgically correctable
      complications (eg, pseudocysts or biliary obstruction). An American
      Gastroenterological Association technical review of painful chronic pancreatitis
      emphasized the lack of controlled studies supporting any form of therapy. Further
      evidence that longstanding chronic pancreatitis is a premalignant condition has
      been provided by recent epidemiologic, pathologic, and molecular biology studies.

PMID- 17023981
TI  - Molecular genetics and related developments in pancreatic cancer.
AB  - Cancer of the pancreas is a genetic disease. The most common genetic alterations
      identified to date in pancreatic cancer are activation of the K-ras oncogene
      (approximately 90%) and inactivation of the p16 (approximately 95%), p53 (50% to
      75%), DPC4 (55%), and BRCA2 (7%) tumor suppressor genes. An understanding of the
      molecular genetics of carcinoma of the pancreas is important because it may help
      explain the aggregation of pancreatic cancer in families and may lead to the
      development of novel tests to detect early cancers. For example, the aggregation
      of pancreatic cancer in some families has been shown to result from inherited
      mutations in cancer-causing genes, and genetic alterations shed from pancreatic
      cancers have been detected in stool specimens. In addition, we believe that an
      improved knowledge of the molecular genetics of pancreatic cancer will lead to
      the development of a new generation of rational and more effective treatments.

PMID- 17023982
TI  - Pancreatic surgery.
AB  - According to epidemiologic studies, the incidence of acute and chronic
      pancreatitis and carcinoma of the pancreas are increasing worldwide. This is the
      result not only of improved diagnostic methods introduced in the last decades
      (eg, contrast-enhanced computed tomography, "all-in-one" magnetic resonance
      imaging, single-photon emission computed tomography, and endoscopic retrograde
      cholangiopancreatography) but also of changes in the environment and nutritional
      behavior. Once a specific diagnosis has been made, the first-choice interventions
      in acute and chronic inflammatory pancreatic diseases are predominantly organ-and
      organ function-preserving surgical procedures. In pancreatic cancer, extended
      radical surgery and multimodal therapies seem to offer the most benefit. This
      article provides an overview of recently published articles focusing on surgical
      treatment options in acute and chronic pancreatitis and carcinoma of the
      pancreas.

PMID- 17023984
TI  - Biliary tract physiology.
AB  - Largely because of the recent development of new experimental models,
      cholangiocytes--the cells lining the bile ducts--are now recognized as important
      contributors to and modulators of bile formation. Recent work elucidating the
      mechanisms and regulation of fluid, solute, and electrolyte transport indicates
      that the biliary epithelium influences bile formation through both autocrine and
      paracrine mechanisms. Novel roles for bile acids in cholangiocyte physiology have
      been proposed, and insight into the anatomic and functional differences of
      cholangiocytes along the biliary tree has been gained. Improved understanding of
      these concepts and the pathophysiologic response of the biliary tree to injury
      should provide new therapies for biliary diseases.

PMID- 17023985
TI  - Biliary tract cancer.
AB  - Recent advances in the molecular and cellular biology, diagnosis, and treatment
      of biliary tract cancer are reviewed. Several studies have delineated the
      molecular and cellular biology of cholangiocarcinoma and gallbladder carcinoma.
      Hepatocyte growth factor seems to be mitogenic to gallbladder carcinoma, and its
      inhibition may have a therapeutic role in this disease. Evidence against an
      adenoma-carcinoma pathway in gallbladder mucosa is presented. Helical computed
      tomography may improve staging accuracy in biliary tract disease and plays a
      definite role in diagnosis of and treatment planning in gallbladder polyps.
      Complete surgical resection continues to provide the best long-term prognosis,
      and surgical drainage is most beneficial in cholangiocarcinoma. Controversy
      continues about the effects of laparoscopic procedures and abdominal wall tumor
      recurrence.

PMID- 17023986
TI  - Sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that
      progresses to death as a result of liver failure or cholangiocarcinoma.
      Susceptibility to PSC is associated with the HLA A1-B8-DR3 haplotype, and new
      associations with HLA C and tumor necrosis factor genes have been detected. A
      circulating antineutrophil cytoplasmic antibody is found in many patients with
      PSC, but its antigen or antigens have not been identified. Some studies suggest
      that this antigen may be an anti-nuclear membrane protein rather than
      cytoplasmic. Diagnosis of PSC is based on endoscopic retrograde cholangiography,
      but magnetic resonance cholangiography is a promising noninvasive alternative.
      Medical treatment remains elusive. In highly selected patients, endoscopic or
      even surgical treatment can be tried. Orthotopic liver transplantation remains
      the only effective therapy, but inflammatory bowel disease may run a more
      aggressive clinical course after this procedure. Sclerosing cholangitis may recur
      after transplantation, but this has had no clinical implications to date.

PMID- 17023987
TI  - Gallstones.
AB  - This review summarizes the main advances made in the epidemiology, pathogenesis,
      and medical treatment of gallstone disease in the past year. Whether rapid weight
      reduction can precipitate gallstone formation is still debated. Phospholipase
      A(2)-II seems to play an interesting role in the pathogenesis of multiple
      cholesterol stone formation, and ursodeoxycholic acid may partially halt the
      formation of multiple cholesterol stones by mediating an anti-inflammatory effect
      on the gallbladder. Bacterial infections may contribute to gallstone formation,
      perhaps through secretion of biofilm. The combination of ursodeoxycholic acid and
      simvastatin for the resolution and prevention of gallstones is promising, but
      larger studies are needed.

PMID- 17023988
TI  - Endoscopic management of biliary tract disease.
AB  - Endoscopic management of biliary tract disease continues to be influenced by new
      advances in technology and shaped by further examination of old controversies.
      This review covers and highlights recent world literature concerning biliary
      endoscopy and its effect on the management of biliary disorders. In particular,
      we examine the role and consequence of the endoscopic management of
      choledocholithiasis and the continuing controversy over endoscopic treatment of
      pancreatic disease. The increasing impact of endoscopic ultrasound in the biliary
      tree is explored, as well as the latest developments in biliary stent technology.

PMID- 17023989
TI  - Bibliography current world literature.

PMID- 17023990
TI  - Stomach and duodenum.

PMID- 17023991
TI  - Regulation of gastric acid secretion.
AB  - This paper summarizes important developments, published over the past year, that
      improve our understanding of the regulation of gastric acid secretion at the
      central, peripheral, and intracellular levels and mechanisms by which various
      neurotransmitters, paracrine agents, and hormones regulate gastric secretion and
      are themselves regulated. The main stimulants of acid secretion from the parietal
      cell are histamine, gastrin, and acetylcholine. Histamine, released from fundic
      enterochromaffin-like cells, interacts with H(2) receptors on parietal cells that
      are coupled via separate G proteins to activation of adenylate cyclase and
      phospholipase C. The antral hormone gastrin, released by activation of
      cholinergic and bombesin/gastrin-releasing peptide neurons, acts mainly by
      release of histamine from enterochromaffin-like cells. Acetylcholine, released
      from gastric intramural neurons, interacts with muscarinic M(3) receptors on
      parietal cells and has little, if any, effect on histamine secretion. The main
      inhibitor of acid secretion is somatostatin, which, acting via sst(2) receptors,
      exerts a tonic restraint on parietal, enterochromaffin-like, and gastrin cells.
      In patients with duodenal ulcer, infection with Helicobacter pylori is associated
      with increased basal and stimulated plasma gastrin concentrations and acid
      outputs. The precise mechanisms mediating the effects are not known, but evidence
      suggests that both products of the bacteria and the inflammatory infiltrate are
      capable of stimulating gastrin and acid secretion.

PMID- 17023992
TI  - Gastroduodenal mucosal defense.
AB  - Research performed in the laboratory and the clinic over the past several years
      has added to our understanding of the mechanisms that are operative in protecting
      the epithelial lining of the stomach and duodenum from injury and ulceration,
      most frequently caused by necrotic agents in the lumen. The defensive mechanism
      of the gastroduodenal mucosa comprises a series of physical, chemical, biologic,
      and immunologic barriers or mechanisms that act in concert to either prevent or
      limit cellular injury or transformation. The field of gastroduodenal defense can
      be subdivided into the following four areas: extracellular mucus barrier
      properties; membrane and ion transport properties; cellular factors promoting
      growth and restitution; and vascular, neural, and inflammatory factors ensuring
      optimal tissue perfusion and immune responsiveness, respectively. In addition, a
      great deal can be learned about gastroduodenal defense by studying the effects of
      ulcerogenic factors and conditions on the defensive mechanisms described here and
      specifically how they may be compromised by nonsteroidal anti-inflammatory drugs
      and Helicobacter pylori infection. This review presents interesting and
      noteworthy findings impacting on these properties contributing to gastroduodenal
      defense since the prior review article on this subject appearing in this journal.

PMID- 17023993
TI  - Nonsteroidal anti-inflammatory drug gastrointestinal toxicity.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used
      class of therapeutic agents. By inhibiting cyclooxygenase (COX) and reducing
      gastrointestinal prostaglandins, they provide effective analgesia and suppress
      inflammation in a variety of conditions. However, through the same mechanism of
      COX inhibition, they also cause significant gastrointestinal toxicity. One of the
      most common methods to reduce NSAID-induced gastrointestinal toxicity has been to
      co-prescribe prophylactic therapies such as acid-reducing agents or the synthetic
      prostaglandin analogue, misoprostol. More recently safer NSAIDs, such as the COX
      2 specific NSAIDs or the nitric oxide-releasing NSAIDs, have been developed or
      are currently in development. This article reviews mechanisms of NSAID-induced
      gastrointestinal toxicity. Also reviewed are data on the gastrointestinal
      consequences of the prophylatic co-therapies, COX-2 specific NSAIDs and nitric
      oxide-releasing NSAIDs.

PMID- 17023994
TI  - Gastroduodenal motility.
AB  - Several major themes emerged over the past year in the area of gastroduodenal
      motility. Mostly, these themes represented extensions of research areas discussed
      in prior reviews in this series rather than the emergence of completely new
      concepts. Thus, for example, considerable emphasis has again been placed on
      regional gastric motor function in dyspepsia and on the role of fundic relaxation
      and accommodation, in particular. Not surprisingly, basic physiologic research
      has also shown a keen interest in the regulation of fundic relaxation. One new
      and exciting development is the recognition of the stomach's role in satiety. The
      spectrum of gastric motor dysfunction in diabetes mellitus continues to be
      explored, and the important role of hyperglycemia in regulating gastric function
      has been further emphasized. More data have been provided on noninvasive
      alternatives to gastric motor function testing, and several studies have looked
      at factors that may influence variability in these various tests. There have been
      few innovations over the past year in the therapeutic arena; rather, the
      indications and limitations of current therapies have been further developed.

PMID- 17023995
TI  - Nonulcer dyspepsia.
AB  - Nonulcer dyspepsia, characterized by unexplained persistent or recurrent
      epigastric pain or discomfort, affects approximately 20% of the general
      population. Symptom-based diagnostic criteria, first developed by an
      international group of experts, have been refined in the past year in an effort
      to increase the applicability of the criteria (Rome II criteria). New disease
      specific questionnaires that were developed to measure quality of life in
      patients with dyspepsia are now available and are expected to be widely used in
      clinical research studies. Studies on the pathophysiology and management of
      nonulcer dyspepsia were other major topics in the past year, including three
      large, well-conducted randomized controlled trials of Helicobacter pylori
      eradication and symptom resolution.

PMID- 17023996
TI  - The treatment of peptic ulcer disease.
AB  - The literature published in the period under review identified some areas of key
      clinical and scientific importance in the treatment of peptic ulcer disease.
      Attention was drawn to the possibility that Helicobacter pylori may be less
      important as an etiologic factor in ulcer disease in the United States than in
      the rest of the world. The usual large number of papers addressed various
      treatment regimens, and the issue of H. pylori resistance to antibiotics was
      prominent. The introduction of the cyclooxygenase enzyme 2 (COX-2)-specific
      inhibitors promises to significantly affect nonsteroidal anti-inflammatory drug
      (NSAID) gastropathy. The review period produced some excellent papers (mainly
      review papers) on this topic, but there is a paucity of peer-reviewed data on the
      clinical application of COX-2 NSAIDs. Perhaps more important is that some
      authors, using a variety of animal models, protested the blithe acceptance of the
      COX-2 concept, questioning the idea of "specificity" and identifying possible
      problems with respect to ulcer healing. Observations of potential clinical
      importance with regard to the phenomenon of acid rebound after proton-pump
      inhibitor therapy were presented, and the role of H. pylori in the management of
      nonulcer dyspepsia remains controversial, despite the publication of three of the
      best-designed studies to date on this important topic.

PMID- 17023997
TI  - Diagnostic and therapeutic endoscopy.
AB  - Endoscopic therapy improves the outcome of nonvariceal upper gastrointestinal
      hemorrhage. Routine second-look procedures may not improve outcome. Patients who
      rebleed after endoscopic therapy for ulcer hemorrhage should be treated by
      further endoscopic therapy, rather than urgent surgery. Thinner endoscopes offer
      adequate visualization with improved patient tolerance, and new endoscopic
      therapeutic methods continue to be evaluated. Stigmata of recent hemorrhage and
      their endoscopic interpretation remain a topic for discussion. The Rockall
      scoring system is validated. Percutaneous endoscopic gastrostomy insertion may be
      possible without prior transillumination of the stomach. Routine use of
      antibiotics prior to insertion reduces wound infection. Percutaneous endoscopic
      gastrostomy feeding is well established, and follow-up studies confirm its value.
      Endoscopic ultrasound is a rapidly developing technique. Its uses and potential
      have evolved, resulting in wider applications in benign disease of the esophagus,
      biliary tree, and pancreas, in addition to its increasing role in the diagnosis
      and staging of malignancy.

PMID- 17023998
TI  - Surgical intervention and understanding of diseases of the stomach and duodenum.
AB  - The stomach and duodenum are organs of complex physiology and cell biology.
      Neoplastic disease of these organs represents a difficult surgical challenge, and
      gastric and duodenal cancer mortality rates remain high despite advances in
      surgical technique, perioperative care, and adjuvant therapy. True "cures" elude
      the surgeon all too often. Fortunately, our understanding of the genetics and
      molecular biology of upper gastrointestinal neoplasms is increasing and is now
      significantly affecting the clinical management of these tumors as surgical
      therapies continue to improve. The care of benign disease of the stomach and
      duodenum is also evolving as medical therapy and surgical technology improve to
      lessen the morbidity associated with peptic ulcer disease and other benign
      conditions. The event that may have the greatest effect on surgical intervention
      in peptic ulcer disease is the Centers for Disease Control and Prevention
      launching of an educational campaign to promote treatment of Helicobacter pylori.
      This article reviews the most significant advances published in the past year on
      surgical intervention of the stomach and duodenum.

PMID- 17023999
TI  - Disorders of the stomach and duodenum in children.
AB  - Over the past year, there have been continued efforts to increase our
      understanding of the epidemiology, natural history, and pathogenic mechanisms of
      Helicobacter pylori infection in children. In an attempt to delineate the
      spectrum of disease associated with this organism, several teams of investigators
      have also examined the association of H. pylori infection with other disorders,
      from food allergy to inflammatory bowel disease. Developmental aspects of gastric
      and duodenal motility, risk factors for gastrointestinal bleeding in pediatric
      intensive care unit patients, and the use of uncooked cornstarch in the treatment
      of dumping syndrome are among other topics covered in this review.

PMID- 17024001
TI  - Intestinal toxins.
AB  - The application of molecular techniques to the study of bacterial pathogenesis
      has made possible discoveries that are changing the way scientists view the
      bacterium-host interaction. Today, research on the molecular basis of the
      pathogenesis of infective diarrheal diseases of necessity transcends established
      boundaries between cell biology, bacteriology, intestinal pathophysiology, and
      immunology. A comprehensive approach has been taken here to outline the most
      recent findings on the interaction between enteric pathogens and their target
      eukaryotic cells through the elaboration of toxins.

PMID- 17024002
TI  - Mucosal T-cell responses to enteric infection.
AB  - Although immunologists typically examine immune responses in peripheral lymphoid
      tissues, mucosal surfaces are the first sites at which most antigens are
      encountered. The role of lymphocytes in the gut-associated lymphoid tissue (GALT)
      in the production of secretory IgA has been well characterized. Although T cells
      of the GALT are located in areas likely to have a key role in cell-mediated
      immunity at mucosal surfaces, the ways in which these cells help defend against
      mucosal infection are only beginning to be understood. This review examines
      mucosal T-cell responses to enteric infection with bacteria, viruses, and
      parasites.

PMID- 17024003
TI  - Probiotics and gut inflammation.
AB  - The intestine's mucosal surface provides a defense barrier against antigens
      encountered by the enteric route. In this system a balance is generated and
      maintained between host and microfloral bacteria. In intestinal inflammation, the
      integrity of the barrier is disrupted, a greater amount of antigens traverses the
      mucosal barrier, and the routes of transport are altered, possibly evoking
      aberrant immune responses and release of proinflammatory cytokines with further
      impairment of the barrier function. Nutritional therapy remains an attractive
      tool in the management of intestinal inflammation. The advances this past year
      are related to the ecologic system provided by specific strains of gut
      microflora, the concept of healthy microflora, and ways in which gut barrier
      function could be strengthened by consumption of mono-and mixed cultures of
      beneficial live microorganisms as probiotics.

PMID- 17024004
TI  - Foodborne infections.
AB  - The role of foodborne infections in the health of the population has become of
      major concern recently. Numerous agents are transmitted in food and water and
      typically result in acute gastroenteritis, although long-term complications such
      as reactive arthritis (due to Salmonella, Yersinia, and Shigella organisms),
      Guillain-Barre syndrome (due to Campylobacter organisms), and renal failure (due
      to Escherichia coli) are now well recognized. The development of FoodNet to
      follow the epidemiology of select foodborne infections in the United States has
      been a major advance in recent years and is now beginning to show interesting
      trends. Our understanding of the pathogenesis of some of the major foodborne
      pathogens, especially Salmonella, is advancing and the genome sequencing of these
      organisms will advance the field further. Of particular concern of late is the
      increasing number of antibiotic-resistant bacterial isolates, especially for
      Salmonella and Campylobacter. Irrespective of their cause, these changes in
      susceptibility patterns pose a major threat to the appropriate treatment of
      patients. Overall, our knowledge of foodborne infections is advancing rapidly,
      but new factors such as the emergence of antibiotic resistance means that
      vigilance must be maintained.

PMID- 17024005
TI  - Basic mechanisms and clinical implications of oral tolerance.
AB  - Oral tolerance is the physiologic mechanism that prevents hypersensitivity to
      food proteins and probably to commensal bacteria. It has also attracted attention
      as a means of administering therapy for autoimmune and inflammatory diseases.
      Although evidence indicates that both clonal inactivation and active regulatory
      mechanisms may play a role and that the induction of these may be determined
      selectively by the feeding regimen used to induce tolerance, the exact mechanisms
      of oral tolerance remain unclear. Here, we discuss recent evidence that fed
      antigens are presented to CD4(+) T cells by antigen-presenting cells (APCs) that
      lack costimulatory activity, resulting in partial activation of T cells followed
      by a state of unresponsiveness. This seems to occur in many tissues of the immune
      system but may be particularly important in the draining mesenteric lymph node.
      Resting dendritic cells may be the predominant population of APCs involved in
      oral tolerance, and conditions that activate dendritic cells allow the induction
      of productive immunity. Conventionally, presentation of antigen in the absence of
      costimulation is thought to induce T-cell anergy, but evidence now indicates that
      anergic T cells can also act as regulatory cells via the production of inhibitory
      mediators or via cognate interactions with APCs and other T cells. We discuss how
      an ability to deactivate APCs may explain bystander suppressor activity in oral
      tolerance, and we consider how the production of transforming growth factor-beta
      or interleukin-10 by Th3 or T regulatory 1 cells may contribute to tolerance in
      vivo. We speculate that both the production of inhibitory mediators and the
      delivery of suppression via cognate interactions may be properties of otherwise
      "anergic" T cells.

PMID- 17024006
TI  - Strategies for developing a Helicobacter pylori vaccine.
AB  - Novel strategies are needed to control infection with Helicobacter pylori.
      Prophylactic and therapeutic immunization against this gastric pathogen is
      possible in animal models, and initial human studies in H. pylori-infected
      subjects showed that immunization with H. pylori urease is both safe and
      immunogenic. In rodents, gastric protection against Helicobacter species
      infection does not depend on the humoral immune response, and a prominent role of
      the major histocompatibility complex II-restricted CD4(+) T-cell response is
      recognized; however, much remains to be learned about the mechanisms of effective
      bactericidal response. A clear understanding of the basic mechanisms of gastric
      immune protection in humans is of the utmost importance for the development of an
      effective human vaccine. More potent vaccines are likely to be required to induce
      protection in humans. The availability of two complete genome sequences of H.
      pylori represents a unique opportunity to identify novel vaccine antigens.
      Multivalent vaccines delivered by recombinant attenuated bacteria or administered
      with nontoxic adjuvants need to be evaluated in relevant models.

PMID- 17024007
TI  - Bibliography current world literature.

PMID- 17024008
TI  - Gastrointestinal infections.

PMID- 17024009
TI  - Bacterial infections of the small intestine and colon.
AB  - Bacterial infections of the small and large intestine are widespread and continue
      to be topics of active research. Surveys document the importance of diarrheal
      disease in many settings. Major breakthroughs in the understanding of pathogenic
      mechanisms (especially the interactions of bacteria and intestinal cells)
      continue, particularly with respect to shigella, salmonella, Yersinia species,
      and enteropathogenic Escherichia coli. Pathogenic mechanisms of other bacteria,
      such as campylobacter and entero-aggregative E. coli, are not well defined.
      Vaccines for cholera and typhoid fever are available, and new vaccines are in
      various stages of development ranging from synthesis of novel constructs to large
      scale field trials. Several candidate vaccines are being exploited as carriers of
      antigens from other pathogens. Extraintestinal complications from salmonella,
      shigella, campylobacter, Yersinia species, and Shiga toxin-expressing E. coli are
      receiving much attention. Genomic sequencing of several of these pathogens is
      underway. The impact of this work is hard to predict, but expectations are high.

PMID- 17024010
TI  - Viral infections of the gastrointestinal tract.
AB  - Viral gastroenteritis is a major public health problem worldwide, and the number
      of identified pathogens continuously increases. Investigators have made
      considerable progress toward understanding both the epidemiology and the
      mechanisms of virus-cell interactions, host responses, and pathogenesis. A
      vaccine for the most important pathogen, rotavirus, has been approved by the US
      Food and Drug Administration, but possible complications have temporarily curbed
      the use of this vaccine.

PMID- 17024011
TI  - Protozoan parasites that infect the gastrointestinal tract.
AB  - Protozoa that infect the gastrointestinal tract include the deadly parasite
      Entamoeba histolytica;Giardia lamblia, the most common cause of waterborne
      disease outbreaks; and the large group of spore-forming parasites that share a
      green algae symbiont and a predilection for causing chronic diarrhea in
      immunocompromised persons. Some recent advances in the epidemiology,
      pathogenesis, diagnosis, and treatment of the diseases caused by these protozoa
      are discussed in this review.

PMID- 17024012
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Helicobacter pylori, a gram-negative, microaerophilic, motile, spiral-shaped
      bacterium, has been established as the etiologic agent of gastritis and peptic
      ulcers and is a major risk factor for gastric adenocarcinoma and mucosa
      associated lymphoid tissue lymphoma (MALT). The ability of H. pylori to cause
      this spectrum of diseases depends on host, bacterial, and environmental factors.
      Bacterial factors critical for H. pylori colonization of the gastric mucosa
      include urease, flagella, adhesins, and delta-glutamyltranspeptidase.
      Lipopolysaccharide, urease, and vacuolating cytotoxin are among the factors that
      allow H. pylori to persist for decades and invoke an intense inflammatory
      response, leading to damaged host cells. Genes in the cag pathogenicity island
      also contribute to the inflammatory response by initiating a signal transduction
      cascade, resulting in interleukin-8 production. Proinflammatory cytokines and a
      Th-1 cytokine response further exacerbates the inflammation. Products of the
      enzymes nitric oxide synthase (iNOS) and cyclooxygenase may perturb the balance
      between gastric epithelial cell apoptosis (ulcer formation) and proliferation
      (cancer). The host Th-1 response and antibodies directed against H. pylori do not
      eliminate the organism, which presents challenges to vaccine development.
      Vaccines that include urease have shown some promise, but improved adjuvants and
      animal models should hasten progress in vaccine research. H. pylori is the most
      genetically diverse organism known, and the panmictic population structure may
      contribute to the varying ranges of disease severity produced by different
      strains. The complete genome sequence of two strains of H. pylori has propelled
      this field forward, and numerous groups are now using genomic, proteomic, and
      mutagenetic approaches to identify new virulence genes. Discovered only in 1982,
      H. pylori is now among the most intensely investigated organisms. This review
      summarizes recent progress in this rapidly moving field.

PMID- 17024013
TI  - Treatment of Helicobacter pylori infection.
AB  - Combination antimicrobial therapies for the effective eradication of Helicobacter
      pylori infection have been identified and are commercially available. Ongoing
      studies to improve eradication rates are based on modification of currently
      approved treatments. Management of H. pylori infection now focuses on which
      patients should be treated and, by extension, which should be tested, because all
      patients should have a positive test result for H. pylori before starting
      antimicrobial therapy. Peptic ulcer disease was believed to be caused by acid
      abnormalities until about two decades ago, when H. pylori was successfully
      cultured; the clinical records of an early proponent of an infectious cause of
      peptic ulcer disease were recently discovered. The role of H. pylori infection in
      gastroesophageal disease and in ulcer disease associated with nonsteroidal anti
      inflammatory drugs have become intensely investigated topics. Consensus
      conferences among pediatric physicians are establishing practice guidelines for
      H. pylori management in children and adolescents.

PMID- 17024014
TI  - Gastrointestinal infections in children.
AB  - New pathogens that cause gastroenteritis in children are being recognized. Even
      well-recognized pathogens, such as Clostridium difficile, may require more
      extensive testing than was previously thought necessary. Several new tests have
      emerged that allow for faster identification of these pathogens so that same-day
      results may be possible. Probiotic therapy has emerged as a novel strategy for
      the treatment of gastroenteritis. New vaccines against both viral and bacterial
      causes of gastroenteritis are being developed. The most exciting recent advance
      in vaccine development may be the creation of edible vaccines.

PMID- 17024015
TI  - Gastrointestinal infections in the immunocompromised host.
AB  - Infectious diseases of the gastrointestinal tract continue to be an important
      source of morbidity and mortality. Viruses, bacteria, fungi, and protozoa that
      infect normal hosts also infect the gastrointestinal tract in immunocompromised
      hosts. Disease caused by these pathogens may be more severe and more difficult to
      treat in immunocompromised hosts. In addition, pathogens that rarely cause
      disease in normal hosts cause significant disease in immunosuppressed hosts.
      Diagnostic decisions need to take into account expected pathogens and response to
      therapy. Treatment decisions must be based on the findings of diagnostic
      procedures; expected pathogens; and recent data suggesting that highly active
      antiretroviral therapy, with its ability to reconstitute immune function, is an
      essential component of treatment. This review summarizes the most important
      developments made in the pathogenesis, clinical presentation, diagnosis, and
      treatment of gastrointestinal infections in immunocompromised hosts in the past
      year.

PMID- 17024016
TI  - Treatment of gastrointestinal infections.
AB  - Treatment of gastrointestinal infections continues to be complicated by expanding
      resistance to antibiotics. This has led to both new antibiotic treatments and to
      research on alternative therapies. In the case of Clostridium difficile colitis,
      interesting preliminary results have been obtained with both probiotic therapy
      and passive immunization strategies. The newer macrolides were found to be
      effective for multidrug-resistant Salmonella typhi and safe in the pediatric
      population. The efficacy of rifaximin, a nonabsorbed antimicrobial agent, was
      demonstrated in the treatment of travelers diarrhea in Mexico. The benefit of the
      proteolytic agent bromelain, which degrades enterocyte receptors for
      enterotoxigenic Escherichia coli, was shown in an experimental model of piglets
      challenged with this infection after bromelain prophylaxis. The potential value
      of zinc supplementation in infant diarrhea was shown in a study in India. The
      recently approved rotavirus vaccine is being withheld because of multiple
      reported cases of intussusception. Cryptosporidiosis continues to challenge old
      and new chemotherapeutic agents. The usefulness of paromomycin in Cryptosporidium
      infection was shown in both murine and piglet models. The cost effectiveness of
      prophylaxis for parasitosis in immigrants has been an area of investigation.

PMID- 17024017
TI  - Defining new pathogens and nonculturable infectious agents associated with
      inflammatory bowel disease.
AB  - The causes of inflammatory bowel disease remain uncertain, but increasing
      evidence supports roles for two pathogenic processes: genetic susceptibility in
      the host and an aberrant host response to enteric bacteria. Here, we review
      studies showing that the pathogenesis of inflammatory bowel disease involves both
      bacterial agents and genetic susceptibilities. We discuss the roles of known and
      novel commensal intestinal bacteria in the pathogenesis of inflammatory bowel
      disease and the various recombinant approaches used to identify these pathogens.

PMID- 17024019
TI  - Genomic instability and colorectal cancer.
AB  - Colon cancer results from the accumulation of genetic alterations. Genomic
      instability creates a permissive state in which a potential cancer cell is
      allowed to acquire enough mutations to become a cancer cell. Several forms of
      genomic instability are common in colon cancer: microsatellite instability (MSI),
      chromosome instability (CIN), and chromosome translocations. MSI occurs in
      approximately 15% of colon cancers and results from inactivation of the mutation
      mismatch repair (MMR) system secondary to either MMR gene mutations or
      hypermethylation of the hMLH1 promoter. It promotes tumorigenesis by generating
      mutations in target genes that possess coding microsatellite repeats, such as the
      transforming growth factor-beta receptor type II gene. CIN occurs in most other
      colon cancers and leads to a different pattern of gene alterations that culminate
      in tumor formation. It seems to result from mutations in genes that control
      mitosis, DNA damage repair, centrosome structure and function, and other
      fundamental processes in DNA replication. The clinical significance of genomic
      instability is now under investigation, and it is hoped that this research will
      soon yield results that have an immediate effect on the treatment of colon
      cancer.

PMID- 17024020
TI  - Role of autocrine and endocrine gastrin-like peptides in colonic carcinogenesis.
AB  - Colon carcinogenesis is a multistep process that involves deletions, mutations,
      and changes in expression of genes that regulate growth, differentiation, and
      apoptosis. Hyperproliferation can initiate dysplastic growth, resulting in
      accumulation of genetic defects and progression of colon cancer. Although genetic
      instability, because of inheritance of specific genetic defects, plays a dominant
      role in familial cancers, in the majority of sporadic cancers hyperproliferation
      is likely to play a permissive role in initiation and progression of the disease.
      Thus factors that regulate growth, differentiation, and apoptosis are likely to
      play an important role in colon carcinogenesis. Autocrine gastrins, insulin-like
      growth factor-II, transforming growth factor-alpha, and endocrine gastrins have
      been implicated in the tumorigenic potential of colon cancer cells. In this
      article we focus on the role of endocrine and autocrine gastrins in colon cancer
      and review recent advances that suggest a role of processing intermediates of
      gastrin in colon carcinogenesis.

PMID- 17024021
TI  - New insights into neural injury, repair, and adaptation in visceral afferents and
      the enteric nervous system.
AB  - In this brief review, we focus on some of the proposed mechanisms of injury in
      peripheral visceral afferents (sensory) pathways and the enteric nervous system,
      including the interstitial cells of Cajal. Injury involving afferent neurons is
      discussed because of the relevance of these neurons to the pathophysiology of
      pain syndromes. The effect of various noxious stimuli on sensory and enteric
      neural function is examined. Finally, we discuss recent data on the role of
      autoimmune antibodies in neuronal injury in systemic diseases, such as diabetes
      mellitus and the Lambert-Eaton myasthenic syndrome. Neither central nervous
      system manifestations of peripheral nerve injury nor functional bowel disorders
      are addressed in this review. An improved understanding of the pathophysiology of
      peripheral neuronal dysfunction will probably result in new treatment strategies
      for a broad range of gastrointestinal disorders, including constipation, pseudo
      obstruction, ileus, and inflammatory bowel disorders.

PMID- 17024022
TI  - Chemokines and cytokines in inflammatory bowel disease and their application to
      disease treatment.
AB  - The term inflammatory bowel disease refers to two chronic, relapsing or
      remitting, inflammatory disorders of the intestinal tract that although somewhat
      similar clinically represent two markedly different and distinct disorders
      histologically, endoscopically, immunologically, and by many other means. The
      pathogenesis of these diseases, ulcerative colitis and Crohn's disease, remains
      unknown and medical and surgical therapy is limited. Approximately 70% of
      individuals with Crohn's disease require surgery with another 40% to 45%
      requiring reoperation, whereas approximately 20% to 25% of patients with
      ulcerative colitis undergo surgical intervention. This review highlights the
      specific clinical features of the disease as well as some of the recent insights
      into the cause of the disease. Standard medical therapy is highlighted and more
      recent biologic therapies including the use of anti-tumor necrosis factor-alpha
      antibodies are described. The changing focus of therapy from nonspecific anti
      inflammatory medications to targeted biologic therapies is reviewed. A number of
      novel therapeutic targets are highlighted and future directions for research and
      clinical testing are discussed.

PMID- 17024023
TI  - Diagnosis and management of lower gastrointestinal bleeding.
AB  - There are few randomized, prospective trials evaluating the optimal diagnostic
      and therapeutic strategies in the management of lower gastrointestinal bleeding.
      However, recent data suggest that urgent colonoscopy represents a safe and
      effective initial diagnostic approach. The role of tagged erythrocyte
      scintigraphy is yet to be defined, but it may be of utility as a screening test
      for visceral angiography. Colonoscopy and angiography both offer substantial
      therapeutic options but remain of unproved benefit from a treatment standpoint;
      surgery continues to play an important role in the management of lower
      gastrointestinal bleeding. Obscure gastrointestinal bleeding, which often
      presents as lower gastrointestinal bleeding, continues to be one of the most
      challenging diagnostic and therapeutic problems in gastroenterology. Occult
      gastrointestinal bleeding, often arising from the lower gastrointestinal tract,
      usually mandates gastrointestinal evaluation.

PMID- 17024024
TI  - Bibliography current world literature.

PMID- 17024026
TI  - Celiac disease.
AB  - Increased awareness of the high prevalence of celiac disease and the degree of
      underdiagnosis has led to calls for routine screening in certain groups. The
      potential consequences of underdiagnosis have been the subject of several
      studies. Where there is a delay in diagnosis, there may be an increased risk of
      associated autoimmune diseases. Alternatively, there may be marked neurological
      complications, or fetal growth retardation where pregnancy preceeds diagnosis.
      Once a diagnosis is obtained, treatment may become easier with further evidence
      that oats are well tolerated by most people with celiac disease. Screening will
      be facilitated by the development of highly sensitive and specific enzyme-linked
      immunosorbent assays for tissue transglutaminase. Further insights into the
      genetics of the condition have been gained with the discovery of a new human
      leukocyte antigen susceptibility type, plus a possible non-human-leukocyte
      antigen susceptibility gene.

PMID- 17024027
TI  - Mucosa-associated lymphoid tissue and other gastrointestinal lymphomas.
AB  - The gastrointestinal tract is the most common site for extranodal lymphomas. The
      most common, and consequently the most studied, gastrointestinal lymphoma is
      gastric mucosa-associated lymphoid tissue lymphoma, which is a paradigm for all
      gastrointestinal lymphomas. Recent advances in oncogenesis, genetics, and
      immunology have all yielded important discoveries that enhance our understanding
      of this lymphoma. The implications of these new advances are beginning to
      translate into changes in therapeutic approach.

PMID- 17024028
TI  - 5-HT (serotonin) physiology and related drugs.
AB  - Alone among organs of the body, the gut is able to mediate reflexes in the
      absence of input from the brain or spinal cord. This ability appears to be caused
      by the secretion of serotonin (5-HT) by enterochromaffin (EC) cells of the
      mucosal epithelium. This 5-HT is secreted into the wall of the gut, where it
      stimulates the mucosal processes of intrinsic and extrinsic primary afferent
      neurons. The intrinsic primary afferents, which are activated by 5-HT1P/4
      receptors, initiate peristaltic and secretory reflexes. The extrinsic primary
      afferent neurons send distress and other signals to the central nervous system.
      Extrinsic nerves are activated by 5-HT(3) receptors. The 5-HT that is involved in
      mucosal signaling is inactivated by uptake into mucosal epithelial cells, which
      are mediated by an integral membrane protein called the serotonin reuptake
      transporter (SERT). The epithelial SERT is the same molecule as that which
      transports 5-HT in the central and enteric nervous systems. Increasing evidence
      suggests that abnormal enteric release or inactivation of 5-HT is involved in the
      pathogenesis of irritable bowel syndrome (IBS). Spread of 5-HT to inappropriate
      sites in IBS may activate 5-HT(3) receptors on extrinsic afferent fibers and
      motor neurons, giving rise to visceral hypersensitivity and abnormal motility,
      respectively. A potent 5-HT(3) antagonist, such as alosetron, can prevent both of
      these effects and is therefore useful in treating IBS. 5-HT also appears to
      function as a growth factor in the development of enteric neurons. The
      developmental effects of 5-HT are mediated by the 5-HT(2B) receptor, which is
      developmentally regulated. The importance of serotonergic mechanisms in enteric
      physiology probably accounts for the gastrointestinal "side effects" of compounds
      that inhibit SERT. The newly discovered role of 5-HT in enteric neuronal
      development suggests that drugs that interfere with the action or inactivation of
      5-HT should be used in pregnancy only with extreme caution, if at all.

PMID- 17024029
TI  - Enteroscopy.
AB  - It is now more than 25 years since small bowel enteroscopy (SBE) was first
      described. For several reasons, this technique developed more slowly than other
      more usual forms of endoscopy. First, small bowel disease is relatively rare in
      comparison with other gastrointestinal diseases. Also, there was lack of initial
      design agreement, and three different types of enteroscopes were developed within
      a short time of each other, two of which (push-type and sonde) are now available
      commercially. Finally, commercial interests of the manufacturers of endoscopes
      were mainly focused on the more conventional, large volume markets. In the last
      few years, specifically designed modern small bowel enteroscopes have become
      available and, in centers that have access to them, they have superseded attempts
      at SBE using adult or pediatric colonoscopes. There are now clear indications for
      SBE, such as: the investigation of obscure causes of bleeding and anemia;
      malabsorption; clarification of x-ray abnormalities; and, increasingly, the
      application of therapeutic endoscopy to lesions within the small bowel. Problem
      areas remain, but with advancing technology and more professional interest in
      this area, these will be addressed during the next few years.

PMID- 17024030
TI  - Small bowel transplantation.
AB  - The development of small bowel transplantation has long been hindered by the
      immunological and infectious barriers peculiar to the small bowel. Gradual
      progress has been achieved during the past decade with the use of tacrolimus and
      the availability of better anti-infection prophylaxis. The current status of
      small bowel transplantation as a life-saving option for patients failing on total
      parenteral nutrition and those who have developed irreversible liver failure is
      undisputed. Small bowel transplantation can be performed as either an intestine
      only graft or as part of a composite graft with the liver and, on occasion, other
      organs. The various techniques of donor and recipient operations are relatively
      standardized. Despite the progress made, the most common causes of death and
      graft loss continue to be sepsis, rejection, and lymphomas. Further progress can
      be achieved by development of more effective immunosuppressive and
      immunomodulatory strategies. The role of inducing chimerism by adjuvant donor
      specific bone marrow transfusions to promote graft tolerance is uncertain. Until
      the mortality and graft losses are further reduced, the role of small bowel
      transplantation will be limited to a salvage procedure for failure of total
      parenteral nutrition rather than a primary treatment of intestinal failure.

PMID- 17024031
TI  - Small intestinal permeability.
AB  - The noninvasive assessment of small intestinal permeability in humans is now
      within the capability of any routine biochemistry laboratory. There remain
      however, many pitfalls for the unwary when performing these tests. Importantly,
      it has now been shown that normal intestinal permeability relates to geographical
      location rather than race. Recent studies show that it may be possible to
      simplify the procedure even further. The main recent focus of interest in
      measuring intestinal permeability relates to patients with AIDS and inflammatory
      bowel disease, the effects of nonsteroidal anti-inflammatory drugs on the small
      bowel, and the use of these tests in the pediatric population and critically ill.
      Some groups have now started to focus their attention on the possible systemic
      consequences of increased intestinal permeability, whereas others have shown that
      increased small bowel permeability results in small intestinal inflammation that
      may in turn be associated with blood and protein loss.

PMID- 17024032
TI  - Small intestine motility.
AB  - During the period of review, work has been ongoing to refine existing techniques
      and to better define normal patterns of small intestinal motility. Researchers
      continue to learn more about the established neurohumoral control mechanisms of
      motility, as well as the effects and potential importance of newly discovered
      neuropeptides and receptors. There has also been continued interest in
      alterations in motility in various disease states and in the effects on motility
      of a number of pharmacologic agents.

PMID- 17024033
TI  - Nutrient absorption.
AB  - Some key advances occurred last year in understanding mechanisms involved in
      nutrient absorption. A novel "prechylomicron transport vesicle" was identified;
      its movement to the Golgi is the rate-limiting step for triacylglycerol
      absorption. A scavenger receptor (type BI) in the brush border membrane appears
      to facilitate cholesterol uptake. Several studies define mechanisms for
      gastrointestinal peptide hormone stimulation of glucose uptake. An oligopeptide
      transporter, PepT1, is transcriptionally upregulated by certain dietary amino
      acids and dipeptides. Surprisingly, both insulin and fasting double the maximum
      velocity for dipeptide uptake (via PepT1), but they act by different mechanisms.
      Three transporters, SMVT (sodium-dependent multivitamin transporter for biotin
      and pantothenate), SVCT (for vitamin C), and CaT1 (for Ca uptake from the lumen)
      have been cloned and are active when expressed in various cells. Additional
      studies provide insights on Ca absorption and vitamin D action in aging, estrogen
      deficiency, and adaptation to a low Ca diet. Nramp2, also called DMT1 (divalent
      metal ion transporter), seems to be a major regulator of transferrin-independent,
      nonheme iron uptake. Finally, the protein HFE associates with the transferrin
      receptor and is part of an iron-sensing mechanism that regulates iron absorption.
      It is defective in hereditary hemochromatosis. HFE and Nramp2 (DMT1) genes are
      reciprocally regulated.

PMID- 17024034
TI  - Is glutamine a unique fuel for small intestinal cells?
AB  - Although the small intestinal mucosa is designed to transport large quantities of
      all nutrients to the blood, the primary nutrients utilized by the enterocyte for
      growth and/or maintenance are quite restricted. The major fuels for the small
      intestinal mucosa are amino acids (glutamine, glutamate, aspartate), whereas
      glucose and fatty acids are of much less importance. Many of the experiments have
      been performed during growth or maintenance of mucosa in small rodents,
      especially the rat, a model in which the adaptation of the intestinal mucosa, at
      least to fasting, is quite different than in humans. A special role has been
      suggested for glutamine as a small intestinal fuel, compared with glutamate and
      aspartate, but the available data do not support this view. Clinical trials of
      glutamine supplementation suggest that, if glutamine has a role, it may be
      related to functions other than those relating to small intestinal function.

PMID- 17024035
TI  - Leptin and the gastrointestinal tract.
AB  - The discovery of leptin in 1990 was the culmination of earlier work which
      recognized that communication between the adipocyte and the hypothalamus was
      important in maintaining body weight. Leptin, which is a 16 kilodalton protein
      encoded by the OB gene, is involved in the regulation of food intake, body
      composition, and energy expenditure through a central feedback mechanism.
      Initially thought to be adipocyte-specific, the OB gene, as well as the leptin
      receptor, have been found in a variety of other tissues. Relevant to this review,
      the leptin gene and its receptor have been identified in the stomach, intestine,
      liver, and pancreas. Recent data also suggest that leptin may act locally within
      the gastrointestinal tract to influence intestinal function. This review
      emphasizes the concept that leptin may be a new gastrointestinal hormone and the
      need to expand the focus of leptin research to include all phases of weight
      maintenance, such as nutrient absorption and utilization, in addition to food
      intake.

PMID- 17024036
TI  - Recent progress in obesity pharmacotherapy.
AB  - Interest in obesity pharmacotherapy is intense, sparked by the public health
      threat of increases in obesity rates, as well as by increased knowledge of the
      biology underlying food intake and energy balance. After a hiatus of more than 20
      years, three new medications approved by the US Food and Drug Administration for
      obesity treatment recently reached the marketplace. One of these,
      dexfenfluramine, has been withdrawn because of fenfluramine's and its isomer's
      association with valvular regurgitation. Sibutramine, a centrally acting reuptake
      inhibitor of monoamines, and orlistat, a pancreatic lipase inhibitor, have been
      approved for long-term obesity treatment. This review covers recent publications
      documenting clinical trial experience with these two agents and updates the
      evidence associating dexfenfluramine and fenfluramine with valvulopathy. As
      obesity rates increase throughout the world and as knowledge expands regarding
      the biology of obesity, an expansion of pharmacologic options for obesity
      treatment is certain.

PMID- 17024037
TI  - Fructo-oligosaccharide malabsorption: benefit for gastrointestinal functions.
AB  - Fructo-oligosaccharides or inulin-type fructans are mixtures of oligomers that
      are composed primarily of beta-D-fructose monomers linked by beta2-1 osidic
      bonds. They are natural constituents of many edible plants. They resist digestion
      and are not absorbed in the upper part of the gastrointestinal tract, but they
      are fermented in the colon. That fermentation produces short-chain fatty acids,
      which acidify the colonic content; increase bacterial biomass and, consequently,
      fecal mass; and modify the composition of the microflora, especially by
      stimulating the growth of bifidobacteria. Fructo-oligosaccharides are thus
      prebiotics and a method of the Association of Official Analytical Chemists exists
      to measure them in food products. Because of this behavior in the
      gastrointestinal tract, inulin-type fructans have a low caloric value compared
      with carbohydrate absorbed in the small intestine, they improve Ca absorption and
      Ca balance, and, at least in experimental models, they inhibit the development of
      chemically induced aberrant crypt foci. Moreover, at a systemic level, they may
      contribute to modulating lipogenesis and reducing triglyceridemia. The data
      reviewed in this article support the classification of inulin-type fructans as
      functional food ingredients for which claims will or should become authorized
      when data for humans become available.

PMID- 17024038
TI  - Resistant starches.
AB  - Initially, it was hoped that resistant starches (ie, starches that enter the
      colon) would have clear advantages in the reduction of colon cancer risk and
      possibly the treatment of ulcerative colitis. Recent studies have confirmed the
      ability of resistant starch to increase fecal bulk, to increase the molar ratio
      of butyrate in relation to other short-chain fatty acids, and to dilute fecal
      bile acids. However, reduction in fecal ammonia, phenols, and N-nitroso compounds
      have not been achieved. At this point the picture from the standpoint of colon
      cancer risk reduction is not clear. Nevertheless, there is a fraction of what has
      been termed resistant starch (RS1), which enters the colon and acts as slowly
      digested, or lente, carbohydrate. Foods in this class are low glycemic index and
      have been shown to reduce the risk of chronic disease. They have been associated
      with systemic physiologic effects such as reduced postprandial insulin levels and
      higher high-density lipoprotein cholesterol levels. Consumption of low glycemic
      index foods has been shown to be related to a reduced risk of type 2 diabetes.
      Type 2 diabetes has in turn been related to a higher risk of colon cancer,
      especially colon cancer deaths. If carbohydrate has a protective role in colon
      cancer prevention, it may lie in the systemic effects of low glycemic index
      foods. The colonic advantages of different carbohydrates, therefore, remain to be
      documented. However, there is reason for optimism about the possible health
      advantages of so-called resistant starches that are slowly digested in the small
      intestine.

PMID- 17024039
TI  - Intravenous nutrition: focus on delivery (3-in-1 bags or not?).
AB  - The practicalities of providing intravenous nutrition support the use of 3-in-1
      bags. However, problems with stability are an important consideration, especially
      because the clinical consequences can be devastating. Infusion sets designed with
      different colored tubing to decrease peroxide formation have been investigated.
      Also, even though high-dose heparin should not be combined with lipid emulsions,
      evidence for prescribing low dose in neonatal practice has been published.
      Furthermore, the largest study testing lipid stability with different drugs
      highlights 23 that should not be combined. Generation of oxalate as a marker of
      vitamin C loss and degradation of cocarboxylase have been investigated. Practical
      guidance has been published on the prevention of copper sulfide and iron
      phosphate precipitates. A study demonstrating that parenteral nutrition admixture
      is a poor growth medium has been reported. Finally, cyclical intravenous feeding
      may have a beneficial effect on the liver through protecting mitochondrial
      function from hypoxic damage.

PMID- 17024040
TI  - Complementary and alternative medicine and gastrointestinal diseases.
AB  - Complementary and alternative medicine (CAM) is becoming increasingly utilized as
      a form of health care, with recent studies suggesting that over 40% of Americans
      use some form of CAM. This has major financial implications for the health care
      industry. Traditional physicians frequently are unaware of CAM use by their
      patients, and there are potential interactions between CAM and traditional forms
      of medical therapy. Many of the medicinal CAM agents have been used for their
      postulated anti-inflammatory and/or antifibrotic effects. CAM is especially
      frequently used in patients with chronic diseases. This review discusses CAM use
      in three types of chronic gastrointestinal diseases--liver disease, irritable
      bowel syndrome and dyspepsia, and inflammatory bowel disease.

PMID- 17024041
TI  - Influenza vaccine 2006-2007.

PMID- 17024042
TI  - A new progestin implant (Implanon) for long-term contraception.

PMID- 17024043
TI  - Gluconeogenesis: re-evaluating the FOXO1-PGC-1alpha connection.
AB  - Increased expression of the gene encoding the enzyme glucose-6-phosphatase
      (G6Pase) contributes to the increased production of glucose by the liver that
      occurs in individuals with diabetes. Puigserver et al. show that the
      transcription factor FOXO1 and the transcriptional co-activator PGC-1alpha act
      synergistically to stimulate the expression of genes in the gluconeogenesis
      pathway and propose that PGC-1alpha acts, in part, directly through FOXO1. Here
      we show that FOXO1 is neither required nor sufficient for the stimulation of
      G6Pase-luciferase fusion gene expression by PGC-1alpha. Our results indicate that
      the transcriptional interaction between FOXO1 and PGC-1alpha is indirect.

PMID- 17024049
TI  - Power and particles.

PMID- 17024047
TI  - To build bridges, or to burn them.

PMID- 17024051
TI  - Climate in court.

PMID- 17024053
TI  - Youthful duo snags a swift Nobel for RNA control of genes.

PMID- 17024054
TI  - Cosmic ripples net physics prize.

PMID- 17024055
TI  - Theorists snap over string pieces.

PMID- 17024056
TI  - Cloners break away from the herd.

PMID- 17024058
TI  - Wikipedia rival calls in the experts.

PMID- 17024057
TI  - Q&A: Fabio Mussi. [Interviewed by Alison Abbott].

PMID- 17024060
TI  - Copycats gear up to dog biotech brands.

PMID- 17024063
TI  - Environmental activism: in the name of nature.

PMID- 17024064
TI  - Driven to market.

PMID- 17024065
TI  - A novel reality.

PMID- 17024067
TI  - Learning from painful experience of disaster.

PMID- 17024068
TI  - Bench-to-bedside solution to funding problems.

PMID- 17024074
TI  - Microbiology: death of a chaperone.

PMID- 17024075
TI  - Atomic physics: quantum leap from light to atoms.

PMID- 17024077
TI  - Cell cycle: complex evolution.

PMID- 17024078
TI  - Earth Science: lost lithium found.

PMID- 17024079
TI  - Microbiology: resurrecting a broken genome.

PMID- 17024080
TI  - Nanotechnology: downsizing SQUIDs.

PMID- 17024082
TI  - Genetics: junk DNA as an evolutionary force.

PMID- 17024083
TI  - Biomechanics: robotic whiskers used to sense features.
AB  - Whiskers mimicking those of seals or rats might be useful for underwater tracking
      or tactile exploration. Several species of terrestrial and marine mammals with
      whiskers (vibrissae) use them to sense and navigate in their environment--for
      example, rats use their whiskers to discern the features of objects, and seals
      rely on theirs to track the hydrodynamic trails of their prey. Here we show that
      the bending moment--sometimes referred to as torque--at the whisker base can be
      used to generate three-dimensional spatial representations of the environment,
      and we use this principle to construct robotic whisker arrays that extract
      precise information about object shape and fluid flow. Our results will
      contribute to the development of versatile tactile-sensing systems for robotic
      applications, and demonstrate the value of hardware models in understanding how
      sensing mechanisms and movement control strategies are interlocked.

PMID- 17024084
TI  - From in vivo to in silico biology and back.
AB  - The massive acquisition of data in molecular and cellular biology has led to the
      renaissance of an old topic: simulations of biological systems. Simulations,
      increasingly paired with experiments, are being successfully and routinely used
      by computational biologists to understand and predict the quantitative behaviour
      of complex systems, and to drive new experiments. Nevertheless, many
      experimentalists still consider simulations an esoteric discipline only for
      initiates. Suspicion towards simulations should dissipate as the limitations and
      advantages of their application are better appreciated, opening the door to their
      permanent adoption in everyday research.

PMID- 17024085
TI  - Transiting extrasolar planetary candidates in the Galactic bulge.
AB  - More than 200 extrasolar planets have been discovered around relatively nearby
      stars, primarily through the Doppler line shifts owing to reflex motions of their
      host stars, and more recently through transits of some planets across the faces
      of the host stars. The detection of planets with the shortest known periods, 1.2
      2.5 days, has mainly resulted from transit surveys which have generally targeted
      stars more massive than 0.75 M(o), where M(o) is the mass of the Sun. Here we
      report the results from a planetary transit search performed in a rich stellar
      field towards the Galactic bulge. We discovered 16 candidates with orbital
      periods between 0.4 and 4.2 days, five of which orbit stars of masses in the
      range 0.44-0.75 M(o). In two cases, radial-velocity measurements support the
      planetary nature of the companions. Five candidates have orbital periods below
      1.0 day, constituting a new class of ultra-short-period planets, which occur only
      around stars of less than 0.88 M(o). This indicates that those orbiting very
      close to more-luminous stars might be evaporatively destroyed or that jovian
      planets around stars of lower mass might migrate to smaller radii.

PMID- 17024086
TI  - Genome-wide genetic analysis of polyploidy in yeast.
AB  - Polyploidy, increased sets of chromosomes, occurs during development, cellular
      stress, disease and evolution. Despite its prevalence, little is known about the
      physiological alterations that accompany polyploidy. We previously described
      'ploidy-specific lethality', where a gene deletion that is not lethal in haploid
      or diploid budding yeast causes lethality in triploids or tetraploids. Here we
      report a genome-wide screen to identify ploidy-specific lethal functions. Only 39
      out of 3,740 mutations screened exhibited ploidy-specific lethality. Almost all
      of these mutations affect genomic stability by impairing homologous
      recombination, sister chromatid cohesion, or mitotic spindle function. We
      uncovered defects in wild-type tetraploids predicted by the screen, and
      identified mechanisms by which tetraploidization affects genomic stability. We
      show that tetraploids have a high incidence of syntelic/monopolar kinetochore
      attachments to the spindle pole. We suggest that this defect can be explained by
      mismatches in the ability to scale the size of the spindle pole body, spindle and
      kinetochores. Thus, geometric constraints may have profound effects on genome
      stability; the phenomenon described here may be relevant in a variety of
      biological contexts, including disease states such as cancer.

PMID- 17024087
TI  - AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP.
AB  - AB5 toxins are produced by pathogenic bacteria and consist of enzymatic A
      subunits that corrupt essential eukaryotic cell functions, and pentameric B
      subunits that mediate uptake into the target cell. AB5 toxins include the Shiga,
      cholera and pertussis toxins and a recently discovered fourth family, subtilase
      cytotoxin, which is produced by certain Shiga toxigenic strains of Escherichia
      coli. Here we show that the extreme cytotoxicity of this toxin for eukaryotic
      cells is due to a specific single-site cleavage of the essential endoplasmic
      reticulum chaperone BiP/GRP78. The A subunit is a subtilase-like serine protease;
      structural studies revealed an unusually deep active-site cleft, which accounts
      for its exquisite substrate specificity. A single amino-acid substitution in the
      BiP target site prevented cleavage, and co-expression of this resistant protein
      protected transfected cells against the toxin. BiP is a master regulator of
      endoplasmic reticulum function, and its cleavage by subtilase cytotoxin
      represents a previously unknown trigger for cell death.

PMID- 17024088
TI  - Electron acceleration from contracting magnetic islands during reconnection.
AB  - A long-standing problem in the study of space and astrophysical plasmas is to
      explain the production of energetic electrons as magnetic fields 'reconnect' and
      release energy. In the Earth's magnetosphere, electron energies reach hundreds of
      thousands of electron volts (refs 1-3), whereas the typical electron energies
      associated with large-scale reconnection-driven flows are just a few electron
      volts. Recent observations further suggest that these energetic particles are
      produced in the region where the magnetic field reconnects. In solar flares,
      upwards of 50 per cent of the energy released can appear as energetic electrons.
      Here we show that electrons gain kinetic energy by reflecting from the ends of
      the contracting 'magnetic islands' that form as reconnection proceeds. The
      mechanism is analogous to the increase of energy of a ball reflecting between two
      converging walls--the ball gains energy with each bounce. The repetitive
      interaction of electrons with many islands allows large numbers to be efficiently
      accelerated to high energy. The back pressure of the energetic electrons
      throttles reconnection so that the electron energy gain is a large fraction of
      the released magnetic energy. The resultant energy spectra of electrons take the
      form of power laws with spectral indices that match the magnetospheric
      observations.

PMID- 17024089
TI  - Quantum teleportation between light and matter.
AB  - Quantum teleportation is an important ingredient in distributed quantum networks,
      and can also serve as an elementary operation in quantum computers. Teleportation
      was first demonstrated as a transfer of a quantum state of light onto another
      light beam; later developments used optical relays and demonstrated entanglement
      swapping for continuous variables. The teleportation of a quantum state between
      two single material particles (trapped ions) has now also been achieved. Here we
      demonstrate teleportation between objects of a different nature--light and
      matter, which respectively represent 'flying' and 'stationary' media. A quantum
      state encoded in a light pulse is teleported onto a macroscopic object (an atomic
      ensemble containing 10 caesium atoms). Deterministic teleportation is achieved
      for sets of coherent states with mean photon number (n) up to a few hundred. The
      fidelities are 0.58 +/- 0.02 for n = 20 and 0.60 +/- 0.02 for n = 5--higher than
      any classical state transfer can possibly achieve. Besides being of fundamental
      interest, teleportation using a macroscopic atomic ensemble is relevant for the
      practical implementation of a quantum repeater. An important factor for the
      implementation of quantum networks is the teleportation distance between
      transmitter and receiver; this is 0.5 metres in the present experiment. As our
      experiment uses propagating light to achieve the entanglement of light and atoms
      required for teleportation, the present approach should be scalable to longer
      distances.

PMID- 17024090
TI  - Rapid subtropical North Atlantic salinity oscillations across Dansgaard-Oeschger
      cycles.
AB  - Geochemical and sedimentological evidence suggest that the rapid climate warming
      oscillations of the last ice age, the Dansgaard-Oeschger cycles, were coupled to
      fluctuations in North Atlantic meridional overturning circulation through its
      regulation of poleward heat flux. The balance between cold meltwater from the
      north and warm, salty subtropical gyre waters from the south influenced the
      strength and location of North Atlantic overturning circulation during this
      period of highly variable climate. Here we investigate how rapid reorganizations
      of the ocean-atmosphere system across these cycles are linked to salinity changes
      in the subtropical North Atlantic gyre. We combine Mg/Ca palaeothermometry and
      oxygen isotope ratio measurements on planktonic foraminifera across four
      Dansgaard-Oeschger cycles (spanning 45.9-59.2 kyr ago) to generate a seawater
      salinity proxy record from a subtropical gyre deep-sea sediment core. We show
      that North Atlantic gyre surface salinities oscillated rapidly between saltier
      stadial conditions and fresher interstadials, covarying with inferred shifts in
      the Tropical Atlantic hydrologic cycle and North Atlantic overturning
      circulation. These salinity oscillations suggest a reduction in precipitation
      into the North Atlantic and/or reduced export of deep salty thermohaline waters
      during stadials. We hypothesize that increased stadial salinities preconditioned
      the North Atlantic Ocean for a rapid return to deep overturning circulation and
      high-latitude warming by contributing to increased North Atlantic surface-water
      density on interstadial transitions.

PMID- 17024091
TI  - Lithium isotope evidence for subduction-enriched mantle in the source of mid
      ocean-ridge basalts.
AB  - 'Recycled' crustal materials, returned from the Earth's surface to the mantle by
      subduction, have long been invoked to explain compositional heterogeneity in the
      upper mantle. Yet increasingly, problems have been noted with this model. The
      debate can be definitively addressed using stable isotope ratios, which should
      only significantly vary in primitive, mantle-derived materials as a consequence
      of recycling. Here we present data showing a notable range in lithium isotope
      ratios in basalts from the East Pacific Rise, which correlate with traditional
      indices of mantle heterogeneity (for example, 143Nd/144Nd ratios). Such co
      variations of stable and radiogenic isotopes in melts from a normal ridge segment
      provide critical evidence for the importance of recycled material in generating
      chemical heterogeneity in the upper mantle. Contrary to many models, however, the
      elevated lithium isotope ratios of the 'enriched' East Pacific Rise lavas imply
      that subducted ocean crust is not the agent of enrichment. Instead, we suggest
      that fluid-modified mantle, which is enriched during residency in a subduction
      zone, is mixed back into the upper mantle to cause compositional variability.

PMID- 17024097
TI  - Cutaneous human papillomaviruses persist on healthy skin.
AB  - Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and
      have also been implicated in non-melanoma skin cancer. For genital HPV types, a
      persistent infection with one of the high-risk types is a prerequisite for the
      development of cervical cancer. However, there is only limited data on whether
      infections with cutaneous HPV types persist over time. Serial forehead swab
      samples collected from 63 volunteers (42 healthy individuals and 31 renal
      transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart,
      were analyzed for HPV using general primer PCR, cloning, and sequencing. Among
      the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and
      71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29)
      had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at
      enrolment and 90% (19/21) at follow-up. A persistent infection was detected in
      33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline
      and the same virus was found at follow-up in 43% (19/44). Persistence was not
      significantly associated with age, sex, immunosuppressive treatment, history of
      warts, or genus of HPV. We conclude that cutaneous HPV infections commonly
      persist over several years on healthy skin.

PMID- 17024098
TI  - Galanin-like peptides exert potent vasoactive functions in vivo.
AB  - The cutaneous vasculature plays a key role in the pathophysiology of inflammatory
      skin diseases. The vascular activity is under the control of the peripheral
      nervous system that includes locally released neuropeptides. Recently, we
      detected receptors for the neuropeptide galanin in association with dermal blood
      vessels, suggesting a role of the galanin-peptide-family in the regulation of the
      cutaneous microvasculature. Therefore, we have investigated galanin and galanin
      like peptide (GALP), a neuropeptide previously only considered to be involved in
      metabolism and reproduction in the central nervous system, for vaso-modulatory
      activity in the murine skin in vivo. Picomole amounts of intradermally injected
      galanin and GALP decreased cutaneous blood flow and inhibited inflammatory edema
      formation. Both the full-length GALP (1-60) and the putative smaller proteolytic
      fragment GALP (3-32) showed similar effects. These activities are most likely
      mediated by galanin receptors galanin receptor subtype 2 (GalR2) and/or galanin
      receptor subtype 3 (GalR3), because reverse transcription-PCR analysis of murine
      skin revealed messenger RNA (mRNA) expression of GalR2 and GalR3 but not of
      galanin receptor subtype 1. The lack of galanin receptor mRNAs in endothelial and
      smooth muscle cells indicates a neuronal localization of these receptors around
      the vessels. These results indicate functional activity of GALP in the periphery
      in vivo and suggest a potential role as an inflammatory modulator.

PMID- 17024099
TI  - Lysophosphatidylcholine mediates melanocyte dendricity through PKCzeta
      activation.
AB  - Melanocytes photoprotect the skin through transfer of melanin-containing
      melanosomes to keratinocytes. Factors that increase melanocyte dendricity
      increase melanosome transfer, and are important for prevention of skin cancer.
      Secretory phospholipase-A2 type X (sPLA2-X) is released by epidermal
      keratinocytes and we have shown that lysophosphatidylcholine (LPC), the main
      lysophospholipid released in response to sPLA2-X activity, stimulates melanocyte
      dendricity. LPC activates protein kinase C (PKC) and increases cAMP in other
      cells. Treatment of melanocytes with sPLA2-X or LPC induced phosphorylation of
      the zeta isoform of PKC, and inhibition of protein kinase C zeta (PKCzeta)
      activity abrogated LPC-dependent dendricity. We have shown previously that the
      guanosine triphosphate-binding proteins Rac and Rho link hormone signaling and
      dendricity in melanocytes. Treatment of melanocytes with LPC induced rapid
      activation of Rac that peaked at 30 minutes; Rho was also activated, but peaked
      earlier and declined faster. Through the use of constitutively active mutants of
      Rac, we show that PKCzeta activation is downstream of Rac. We conclude that the
      primary signaling pathway for LPC-dependent dendrite formation in human
      melanocytes involves the activation of PKCzeta and that PKCzeta phosphorylation
      is Rac dependent. Downstream mediators of LPC-dependent dendricity include Rac
      and Rho.

PMID- 17024100
TI  - Functional implications of the IL-6 signaling pathway in keloid pathogenesis.
AB  - The molecular mechanism(s) behind keloid pathogenesis remains unclear. Previously
      by global gene expression analysis of keloid fibroblasts (KFs), we implicated the
      IL-6 signaling pathway in keloid pathogenesis. Here, we determine a functional
      role of IL-6 signaling in keloid scars. Primary cultures of KFs and surrounding
      nonlesional fibroblasts (NFs) were subjected to induction or inhibition of IL-6
      or its specific receptor IL-6 receptor alpha (IL-6R alpha) and detection of their
      effects on extracellular matrix gene expression. The levels of gp130 and several
      downstream targets in IL-6 signaling were also examined. IL-6 secretion was
      significantly higher in KFs than NFs. Addition of IL-6 peptide to NFs culture or
      inhibition of IL-6 or its receptor IL-6R alpha by their corresponding antibodies
      in KFs culture revealed a dose-dependent increase or decrease in collagen type I
      alpha 2 and fibronectin 1 mRNAs, respectively. Induction of IL-6 by IL-1beta
      peptide and stimulation by IL-6 peptide in NFs, or inhibition of IL-6 or IL-6R
      alpha in KFs cultures demonstrated a dose-dependent increase or decrease in
      procollagen I synthesis, respectively. The mRNA and protein expressions of gp130
      and several downstream targets in IL-6 signaling (JAK1, STAT3, RAF1, and ELK1)
      were upregulated in KFs versus NFs. Our results indicate that IL-6 signaling may
      play an integral role in keloid pathogenesis and provide clues for development of
      IL-6 receptor blocking strategies for therapy or prophylaxis of keloid scars.

PMID- 17024101
TI  - Highly efficient and specific modulation of cardiac calcium homeostasis by
      adenovector-derived short hairpin RNA targeting phospholamban.
AB  - Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum
      Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF).
      PLB downregulation may increase SERCA2a activity and improve cardiac function.
      Small interfering (si)RNAs mediate efficient gene silencing by RNA interference
      (RNAi). However, their use for in vivo gene therapy is limited by siRNA
      instability in plasma and tissues, and by low siRNA transfer rates into target
      cells. To address these problems, we developed an adenoviral vector (AdV)
      transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential
      to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in
      primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector
      transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of
      infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left),
      whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I
      protein remained unchanged. PLB silencing was associated with a marked increase
      in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+),
      and rapid loss of responsiveness to protein kinase A-dependent stimulation of
      Ca(2+) uptake was maintained until day 7. In summary, these results indicate that
      AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene
      silencing and modulation of active Ca(2+) sequestration in PNCMs. The
      availability of the new vector now enables employment of RNAi for the treatment
      of HF in vivo.

PMID- 17024102
TI  - Therapeutic RNA interference of malignant melanoma by electrotransfer of small
      interfering RNA targeting Mitf.
AB  - Microphthalmia-associated transcription factor (Mitf) is critically involved in
      melanin synthesis as well as differentiation of cells of the melanocytic lineage.
      Some earlier studies suggested that Mitf is also essential in the survival of
      melanoma cells, but this notion remains controversial. We synthesized short
      interfering RNA (siRNA) duplexes corresponding to the mitf sequence and
      transfected them into B16 melanoma. Lipid-mediated transfection in vitro of Mitf
      specific siRNA resulted in specific downregulation of Mitf and of the tyrosinase
      that is a transcriptional target of Mitf. This treatment also remarkably reduced
      the viability of melanoma cells by inducing apoptosis. To examine the potential
      feasibility of RNAi therapy against melanoma, B16 cells were subcutaneously
      injected into syngenic mice and siRNA was transfected into the pre-established
      tumor by means of electroporation. The Mitf-specific siRNA drastically reduced
      outgrowth of subcutaneous melanoma, while nonspecific siRNA failed to affect
      tumor progression. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling-based analysis of tumor specimens demonstrated that the tumor
      cells transfected with Mitf-siRNA effectively underwent apoptosis in vivo. The
      present results indicate that Mitf plays important roles in melanoma survival.
      Intratumor electrotransfer of Mitf-specific siRNA may provide a powerful strategy
      for therapeutic intervention of malignant melanoma.

PMID- 17024103
TI  - Delivery and mechanistic considerations for the production of knock-in mice by
      single-stranded oligonucleotide gene targeting.
AB  - Single-stranded oligodeoxynucleotide (ssODN) gene targeting may facilitate animal
      model creation and gene repair therapy. Lipofection of ssODN can introduce point
      mutations into target genes. However, typical efficiencies in mouse embryonic
      stem cells (ESC) are <10(-4), leaving corrections too rare to effectively
      identify. We developed ESC lines with an integrated mutant neomycin resistance
      gene (Tyr22Ter). After targeting with ssODN, repaired cells survive selection in
      G418. Correction efficiencies varied with different lipofection procedures,
      clonal lines, and ssODN designs, ranging from 1 to 100 corrections per million
      cells plated. Uptake studies using cell sorting of Cy5-labelled ssODN showed 40%
      of the corrections concentrated in the best transfected 22% of cells. Four
      different basepair mismatches were tested and results show that the base
      specificity of the mismatch is critical. Dual mismatch ssODN also showed mismatch
      preferences. These ESC lines may facilitate development of improved ssODN
      targeting technologies for either animal production or ex vivo gene therapy.

PMID- 17024104
TI  - Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion
      and metastasis.
AB  - Melanoma patients with metastases have a very low survival rate and limited
      treatment options. Therefore, the targeting of melanoma cells when they begin to
      invade and metastasize would be beneficial. An adhesion molecule that is
      upregulated at the vertical growth phase is the melanoma cell adhesion molecule
      (MCAM/MUC18). MUC18 is expressed in late primary and metastatic melanoma with
      little or no expression on normal melanocytes. We utilized the alphavirus-based
      DNA plasmid, SINCp, encoding murine MUC18 (SINCp c-muMUC18) for vaccination
      against B16F10 murine melanoma cells expressing murine MUC18. This vaccine
      effectively protected mice from lethal challenges with melanoma-expressing murine
      MUC18 in both primary and metastatic tumor models. Vaccination against MUC18
      elicited effective humoral and CD8+ T-cell immune responses against melanoma. We
      propose that targeting molecules important in tumor invasion may be useful in the
      design of future strategies for the prevention and treatment of melanoma.

PMID- 17024105
TI  - Restoration of vision in RPE65-deficient Briard dogs using an AAV serotype 4
      vector that specifically targets the retinal pigmented epithelium.
AB  - Previous studies have tested gene replacement therapy in RPE65-deficient dogs
      using recombinant adeno-associated virus 2/2 (rAAV2/2), -2/1 or -2/5 mediated
      delivery of the RPE65 gene. They all documented restoration of dark- and light
      adapted electroretinography responses and improved psychophysical outcomes. Use
      of a specific RPE65 promoter and a rAAV vector that targets transgene expression
      specifically to the RPE may, however, provide a safer setting for the long-term
      therapeutic expression of RPE65. Subretinal injection of rAAV2 pseudotyped with
      serotype 4 (rAAV2/4) specifically targets the RPE. The purpose of our study was
      to evaluate a rAAV2/4 vector carrying a human RPE65cDNA driven by a human RPE65
      promoter, for the ability to restore vision in RPE65-/- purebred Briard dogs and
      to assess the safety of gene transfer with respect to retinal morphology and
      function. rAAV2/4 and rAAV2/2 vectors containing similar human RPE65 promoter and
      cDNA cassettes were generated and administered subretinally in eight affected
      dogs, ages 8-30 months (n = 6 with rAAV2/4, n = 2 with rAAV2/2). Although
      fluorescein angiography and optical coherence tomography examinations displayed
      retinal abnormalities in treated retinas, electrophysiological analysis
      demonstrated that restoration of rod and cone photoreceptor function started as
      soon as 15 days post-injection, reaching maximal function at 3 months post
      injection, and remaining stable thereafter in all animals treated at 8-11 months
      of age. As assessed by the ability of these animals to avoid obstacles in both
      dim and normal light, functional vision was restored in the treated eye, whereas
      the untreated contralateral eye served as an internal control. The dog treated at
      a later age (30 months) did not recover retinal function or vision, suggesting
      that there might be a therapeutic window for the successful treatment of RPE65-/-
      dogs by gene replacement therapy.

PMID- 17024106
TI  - Human blood late outgrowth endothelial cells for gene therapy of cancer:
      determinants of efficacy.
AB  - Human adult blood late outgrowth endothelial cells (BOECs) are potential yet
      untested cellular vehicles to target tumor-cytotoxic effectors to tumors. We show
      that, following intravenous injection into irradiated mice, BOECs home to Lewis
      lung carcinoma (LLC) lung metastases, but less so to liver or kidney metastases.
      BOECs targeted most but not all of the lung metastases, to a different degree.
      While most of the homed BOECs took up an extravascular position, some integrated
      into tumor vessels. Sequestration into normal tissue was low. Placental growth
      factor mediated both migration and invasion of BOECs into LLC spheroid masses in
      vitro, as did VEGF. When armed with a suicide gene, BOECs exerted a bystander
      effect on LLC cells in vitro and in vivo. Surprisingly, i.v. administration of
      armed BOECs into mice bearing multi-organ LLC metastases did not prolong
      survival. In addition to homing efficacy other parameters impacted upon the
      efficacy of BOECs. These include the ultimate susceptibility of BOECs to suicide
      gene-induced cell death, their paracrine proliferative effect on LLC cells and
      their low proliferation rate compared to LLC cells. Addressing these determinants
      may make BOECs a useful addition to the arsenal of tumor-targeting moieties.

PMID- 17024107
TI  - Liver transduction with a simian virus 40 vector encoding insulin-like growth
      factor I reduces hepatic damage and the development of liver cirrhosis.
AB  - Liver transplantation is the only treatment for advanced liver cirrhosis.
      Therapies halting the progression of the disease are urgently needed.
      Administration of recombinant insulin-like growth factor-I (rIGF-I) induces
      hepatoprotective effects in experimental cirrhosis. Therefore, we analyzed the
      efficacy of a recombinant simian virus 40 vector (rSV40) encoding IGF-I (rSVIGF
      I) to prevent cirrhosis progression. First, transgene expression was evaluated in
      mice injected with rSV40 encoding luciferase, which showed long-term hepatic
      expression of the transgene. Interestingly, luciferase expression increased
      significantly in CCl(4)-damaged livers and upon IGF-I administration, thus liver
      injury and IGF-I expression from rSVIGF-I should favor transgene expression.
      rSVIGF-I therapeutic efficacy was studied in rats where liver cirrhosis was
      induced by CCl(4) inhalation during 36 weeks. At the end of the study, the
      hepatic levels of IGF-I and IGF-binding protein 3 were higher in rSVIGF-I-treated
      rats than in control cirrhotic animals. Cirrhotic rats treated with rSVIGF-I had
      reduced serum bilirubin, transaminases and liver fibrosis scores and increased
      hepatic expression of hepatocyte growth factor and STAT3alpha as compared to
      cirrhotic animals. Furthermore, cirrhotic animals showed testis atrophy and
      altered spermatogenesis, whereas testicular size and histology were normal in
      cirrhotic rats that received rSVIGF-I. Therefore, rSV40-mediated sustained
      expression of IGF-I in the liver slowed cirrhosis progression.

PMID- 17024108
TI  - High-performance liquid chromatography method for rapid assessment of viral
      particle number in crude adenoviral lysates of mixed serotype.
AB  - Accurate adenovirus (Ad) quantification requires labor- and time-intensive viral
      stock purification. While crude viral lysates can be titered by plaque assay,
      this cell-based assay is neither rapid nor accurate. Consequently, a method for
      quantification of crude, unpurified viral culture lysates is needed. Given
      growing interest in alternative Ad serotypes (different from well-studied and
      characterized serotype Ad5) for basic research and for therapeutic applications,
      such a method should also apply to alternative serotypes. Using a Q Sepharose XL
      (QSXL) column-based method, we describe a robust quantification method resulting
      in efficient retention of viral particles of all serotypes, while non-viral
      components of crude infected cultures remain largely in the flow-through. The
      high-performance liquid chromatography-QSXL method allows rapid, accurate
      adenoviral quantification in crude lysates as well as identification of the
      various serotypes present in mixed-serotype crude lysates. We also report on
      conditions that efficiently strip and regenerate the column, extending its
      functional life.

PMID- 17024109
TI  - Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy
      with radiotherapy in a preclinical model of metastatic prostate cancer.
AB  - We investigated the potential benefits of combining adenoviral vector mediated in
      situ interleukin-12 (AdmIL-12) gene therapy with radiation therapy (XRT) to
      enhance therapeutic efficacy. In a metastatic mouse prostate cancer cell line,
      178-2 BMA, AdmIL-12+XRT demonstrated enhanced therapeutic activities in vitro as
      determined by clonogenic survival, apoptosis, and mIL-12 levels. At the molecular
      level, increased expression of tumor necrosis factor-alpha mRNA was specific for
      the combined therapy. In a subcutaneous 178-2 BMA in vivo model, the combination
      of AdmIL-12+XRT produced statistically significant tumor growth suppression
      compared to control vector Adbetagal, Adbetagal XRT, or AdmIL-12 as monotherapy.
      In addition, significant prolongation of survival was demonstrated for the
      combination of AdmIL-12+XRT. The combination of AdmIL-12+XRT significantly
      suppressed both spontaneous and pre-established lung metastases, and led to a
      prolonged elevation of serum IL-12 and significantly increased natural killer
      (NK) activities. Importantly, in vivo depletion of NK cells resulted in
      significant attenuation of the antimetastatic activities of AdmIL-12 alone or
      AdmIL-12+XRT. These combined effects suggest that AdIL-12 gene therapy together
      with radiotherapy may achieve maximal tumor control (both local and systemic) in
      selected prostate cancer patients via radio-gene therapy induced local
      cytotoxicity and local and systemic antitumor immunity.

PMID- 17024110
TI  - Magnetic resonance imaging evidence of cytotoxic cerebral edema in acute mountain
      sickness.
AB  - The present study applied T2- and diffusion-weighted magnetic resonance imaging
      to examine if mild cerebral edema and subsequent brain swelling are implicated in
      the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were
      examined in normoxia (21% O2), after 16 hours passive exposure to normobaric
      hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6
      hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during
      hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus
      non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0+/-4.8
      ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery.
      Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a
      general trend toward an increased apparent diffusion coefficient (ADC). During
      the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline
      values, whereas a more marked reduction in ADC in the splenium of the corpus
      callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were
      not selectively different in AMS, ADC values were consistently lower (P<0.05
      versus non-AMS) and associated with the severity of neurologic symptoms. Acute
      mountain sickness was also characterized by an increased brain to intracranial
      volume ratio (P<0.05 versus non-AMS). These findings indicate that mild
      extracellular vasogenic edema contributes to the generalized brain swelling
      observed at high altitude, independent of AMS. In contrast, intracellular
      cytotoxic edema combined with an anatomic predisposition to a 'tight-fit' brain
      may prove of pathophysiologic significance, although the increase in brain volume
      in hypoxia was only about 0.5% of total brain volume.

PMID- 17024111
TI  - Transition from EML1-ABL1 to NUP214-ABL1 positivity in a patient with acute T
      lymphoblastic leukemia.

PMID- 17024112
TI  - PASD1, a DLBCL-associated cancer testis antigen and candidate for lymphoma
      immunotherapy.

PMID- 17024113
TI  - t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the
      HMGA2 gene.

PMID- 17024114
TI  - The Akt signaling pathway determines the different proliferative capacity of
      chronic lymphocytic leukemia B-cells from patients with progressive and stable
      disease.
AB  - Chronic lymphocytic leukemia (CLL) B-cells are hyporesponsive to many
      proliferative signals that induce activation of normal B-lymphocytes. However, a
      heterogeneous response has recently been observed with immunostimulatory CpG
      oligodeoxynucleotides (CpG ODN). We now show that CpG ODN induce proliferation
      mainly in CLL B-cells from patients with progressive disease and unmutated
      immunoglobulin V(H) genes, whereas G(1)/S cell cycle arrest and apoptosis are
      induced in leukemic B-cells from stable/V(H) mutated CLL. Examination of early
      signaling events demonstrated that all CLL B-cells respond to CpG ODN stimulation
      by degradation of the NF-kappaB inhibitor IkappaB and activation of the Akt, ERK,
      JNK and p38 MAPK kinases, but the magnitude and duration of the signaling
      response was greater in the proliferating cases. Pharmacological inhibition of
      these pathways showed that simultaneous activation of Akt, ERK and JNK is
      required for cell cycle progression and proliferation. Conversely, introduction
      of constitutively active Akt in nonproliferating CLL B-cells resulted in
      induction of cyclin A following CpG ODN stimulation, indicating that increased
      Akt activation is sufficient to overcome the hyporesponsiveness of these cells to
      proliferative signals. Thus, the magnitude of Akt signaling may determine the
      distinct responses observed in leukemic B-cells belonging to the different
      prognostic subgroups.

PMID- 17024115
TI  - Activity patterns of proteasome subunits reflect bortezomib sensitivity of
      hematologic malignancies and are variable in primary human leukemia cells.
AB  - Proteasomal proteolysis relies on the activity of six catalytically active
      proteasomal subunits (beta1, beta2, beta5, beta1i, beta2i and beta5i). Applying a
      functional proteomics approach, we used a recently developed activity-based, cell
      permeable proteasome-specific probe that for the first time allows differential
      visualization of individual active proteasomal subunits in intact primary cells.
      In primary leukemia samples, we observed remarkable variability in the amounts of
      active beta1/1i-, beta2/2i- and beta5/5i-type of subunits, contrasting with their
      constant protein expression. Bortezomib inhibited beta5- and beta1-type, but to a
      lesser extend beta2-type of subunits in live primary cells in vitro and in vivo.
      When we adapted the bortezomib-sensitive human acute myeloid leukemia cell line
      HL-60 to bortezomib 40 nM (HL-60a), proteasomal activity profiling revealed an
      upregulation of active subunits, and residual beta1/beta5-type of activity could
      be visualized in the presence of bortezomib 20 nM, in contrast to control cells.
      In a panel of cell lines from hematologic malignancies, the ratio between beta2
      type and (beta1 + beta5)-type of active proteasomal polypeptides mirrored
      different degrees of bortezomib sensitivity. We thus conclude that the
      proteasomal activity profile varies in primary leukemia cells, and that the
      pattern of proteasomal subunit activity influences the sensitivity of hematologic
      malignancies toward bortezomib.

PMID- 17024117
TI  - Philadelphia chromosome unmasked as a secondary genetic change in acute myeloid
      leukemia on imatinib treatment.

PMID- 17024116
TI  - Prognostic and biological implications of genetic abnormalities in multiple
      myeloma undergoing autologous stem cell transplantation: t(4;14) is the most
      relevant adverse prognostic factor, whereas RB deletion as a unique abnormality
      is not associated with adverse prognosis.
AB  - Fluorescence in situ hybridization (FISH) has become a powerful technique for
      prognostic assessment in multiple myeloma (MM). However, the existence of
      associations between cytogenetic abnormalities compels us to re-assess the value
      of each abnormality. A total of 260 patients with MM at the time of diagnosis,
      enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH
      in order to ascertain the independent influence on myeloma prognosis of IGH
      translocations, as well as RB and P53 deletions. Survival analyses showed that
      patients with t(4;14), RB or P53 deletions had a significantly shorter survival
      than patients without these abnormalities. However, patients with RB deletions
      without other abnormalities in FISH analysis, displayed a similar outcome to
      those patients without genetic changes by FISH (46 vs 54 months, P=0.3). In the
      multivariate analysis the presence of t(4;14), RB deletion associated with other
      abnormalities, age >60 years, high proportion of S-phase cells and advanced stage
      of the disease according to the International Staging System retained their
      independent prognostic influence. In summary, RB deletion as a sole abnormality
      does not lead to a shortening in the survival of MM patients, whereas t(4;14)
      confers the worst prognosis in MM patients treated with high-dose chemotherapy.

PMID- 17024118
TI  - Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and
      increase CKS1B expression in myeloma.
AB  - A specific role for increased level of expression of CKS1B, as a consequence of
      chromosome 1q21 copy number gain, has been postulated as both pathogenic, as well
      as a powerful clinical prognostic factor in multiple myeloma (MM). The purpose of
      this study is to determine the clinical associations and prognostic impact of
      copy number gain at chromosome 1q21 (with a bacteria artificial chromosome clone
      containing CKS1B) and CKS1B gene level of expression in MM. We studied the
      chromosome region 1q21 for copy number change in a cohort of myeloma patients
      treated by high-dose therapy with stem-cell rescue (HDT) (n = 159). A separate
      cohort of patients, treated by HDT was studied for CKS1B messenger RNA expression
      by gene expression profiling (n = 67). 1q21 gain was then correlated with
      clinical parameters and survival. Gain of 1q21 copy number was detected in about
      a third of MM and was associated with more proliferative disease and poor-risk
      cytogenetic categories such as t(4;14), and chromosome 13 deletion. Both 1q21
      gain and increase gene expression level were significantly associated with
      reduced survival. However, neither is an independent prognostic marker in MM on
      multivariate Cox proportional hazard analysis.

PMID- 17024119
TI  - Association with the single-nucleotide polymorphism (Glu785Lys) of the
      granulocyte colony-stimulating factor receptor with myelodysplastic syndromes and
      acute myeloid leukemia with multlineage dysplasia.

PMID- 17024120
TI  - The relationship between the systemic inflammatory response, tumour proliferative
      activity, T-lymphocytic infiltration and COX-2 expression and survival in
      patients with transitional cell carcinoma of the urinary bladder.
AB  - The relationship between the systemic inflammatory response, tumour proliferative
      activity, T-lymphocytic infiltration, and COX-2 expression and survival was
      examined in patients with transitional cell carcinoma of the urinary bladder
      (n=103). Sixty-one patients had superficial disease and 42 patients had invasive
      disease. Cancer-specific survival was shorter in those patients with invasive
      compared with superficial bladder cancer (P<0.001). On univariate analysis,
      stratified by stage, increased Ki-67 labelling index (P<0.05), increased COX-2
      expression (P<0.05), C-reactive protein (P<0.05) and adjuvant therapy (P<0.01)
      were associated with poorer cancer-specific survival. On multivariate analysis of
      these significant factors, stratified by stage, only C-reactive protein (HR 2.89,
      95% CI 1.42-5.91, P=0.004) and adjuvant therapy (HR 0.29, 95% CI 0.14-0.62,
      P=0.001) were independently associated with poorer cancer-specific survival.
      These results would suggest that tumour-based factors such as grade, COX-2
      expression or T-lymphocytic infiltration are subordinate to systemic factors such
      as C-reactive protein in determining survival in patients with transitional cell
      carcinoma of the urinary bladder.

PMID- 17024121
TI  - (18)FDG uptake during induction chemoradiation for oesophageal cancer fails to
      predict histomorphological tumour response.
AB  - To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG
      PET) could predict the pathological response in oesophageal cancer after only the
      first week of neoadjuvant chemoradiation. Thirty-two patients with localised
      oesophageal cancer had a pretreatment PET scan and a repeat after the first week
      of chemoradiation. The change in mean maximum standardised uptake value (SUV) and
      volume of metabolically active tissue (MTV) was compared with the tumour
      regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and
      2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV
      fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070).
      In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8),
      respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3
      (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7)
      to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between
      responders and nonresponders. The hypothesis that early repeat FDG-PET scanning
      may predict histomorphologic response was not proven. This may reflect an
      inflammatory effect of radiation that obscures tumour-specific metabolic changes
      at this time. This assessment may have limited application in predicting response
      to multimodal regimens for oesophageal cancer.

PMID- 17024122
TI  - Family history of breast cancer and young age at diagnosis of breast cancer
      increase risk of second primary malignancies in women: a population-based cohort
      study.
AB  - Among 152 600 breast cancer patients diagnosed during 1958-2000, there was a 22%
      increased risk of developing a second primary non-breast malignancy (standardised
      incidence ratio (SIR)=1.22; 95% confidence interval (CI): 1.19-1.24). The highest
      risk was seen for connective tissue cancer (SIR=1.78; 95% CI: 1.49-2.10).
      Increased risks were noted among women diagnosed with breast cancer before age
      50. Oesophagus cancer and non-Hodgkin's lymphoma showed six- and four-fold higher
      risks, respectively, in women with a family history of breast cancer compared to
      those without in the > or =10-year follow-up period.

PMID- 17024123
TI  - Targeting sphingosine-1-phosphate for cancer therapy.
AB  - This review summarises some important new findings that implicate sphingosine-1
      phosphate (S1P) as a potent tumorigenic and angiogenic agent released from
      cancerous tumours into the tumour microenvironment. Also explored is the novel
      concept that bioactive lipid signalling molecules, like S1P, can themselves be
      targets for rational drug design, thereby opening up an entire class of lipidomic
      based therapeutics for oncology and other human diseases.

PMID- 17024124
TI  - Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent
      glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia
      (GICNO).
AB  - The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl
      transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose
      protracted temozolomide administration can decrease AGAT activity. The main end
      point of the present study was therefore to test progression-free survival at 6
      months (PFS-6) in glioblastoma patients following a prolonged temozolomide
      schedule. Chemonaive glioblastoma patients with disease recurrence or progression
      after surgery and standard radiotherapy were considered eligible. Chemotherapy
      cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until
      disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was
      determined in 22 patients (66.7%). A total of 33 patients (median age 57 years,
      range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall
      response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found
      between the MGMT promoter methylation status of the tumours and the overall
      response rate, time to progression and survival. In 153 treatment cycles
      delivered, the most common grade 3/4 event was lymphopoenia. The prolonged
      temozolomide schedule considered in the present study is followed by a high PFS-6
      rate; toxicity is acceptable. Further randomised trials should therefore be
      conducted to confirm the efficacy of this regimen.

PMID- 17024126
TI  - Study design and statistics in the epidemiology of breast cancer.

PMID- 17024127
TI  - The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens.
AB  - We used SEREX technology to identify novel tumour-associated antigens in patients
      with primary hepatocellular carcinoma and found serological responses to the
      polycomb group (PcG) protein BMI-1, which is overexpressed in a range of
      different tumour types. Further studies identified T-cell responses to both BMI-1
      and another PcG protein, EZH2, in cancer patients and at relatively lower levels
      in some normal donors. We next identified several CD8+ T-cell epitopes derived
      from BMI-1 and EZH2 and demonstrated that EZH2-derived peptides elicited more
      significant interferon-gamma (IFN-gamma) release than BMI-1-derived peptides.
      That CD8(+) T cells were responsible for the observed responses was confirmed for
      EZH2 by both IFN-gamma capture assays and tetramer staining using an HLA-A0201
      restricted, EZH2-derived YMSCSFLFNL (aa 666-674) epitope. The ability of
      YMSCSFLFNL (aa 666-674) to stimulate the in vitro expansion of specific T cells
      from peripheral blood lymphocytes was greatly enhanced when the CD25(+) T-cell
      population was depleted. EZH2-specific cytotoxic T lymphocyte clones specific for
      two HLA-A0201 epitopes were generated and found to recognise endogenously
      processed EZH2 in both HLA-matched fibroblasts and tumour cell lines. Given the
      widespread overexpression of PcG proteins in cancer and their critical role in
      oncogenesis, these data suggest that they may be useful targets for cancer
      immunotherapy.

PMID- 17024129
TI  - Complex genetic control of susceptibility to Mycobacterium bovis (Bacille
      Calmette-Guerin) infection in wild-derived Mus spretus mice.
AB  - Susceptibility to Mycobacterium bovis Bacille Calmette-Guerin (BCG) is
      genetically controlled by Nramp1 (Slc11a1). Inbred mouse strains harbor either
      the resistance (Nramp1(G169)) or the susceptibility (Nramp1(D169)) allele at
      Nramp1. Mus spretus (Nramp1(G169); SPRET/EiJ) is shown to display an intermediate
      level of BCG replication in the spleen (log(10) colony-forming units (CFU)
      approximately 5), compared to resistant A/J (log(10)CFU approximately 4.0) and
      susceptible C57BL/6J (log(10)CFU approximately 6.0) mice. The presence of genetic
      modifiers of Nramp1-dependent susceptibility to M. bovis (BCG) infection in Mus
      spretus was analyzed by whole-genome scanning in 175 mice of an informative
      (C57BL/6J x SPRET/EiJ) x C57BL/6J backcross. Nramp1 showed a major effect
      (D1Mcg4, P<1e(-4)), but additional single marker effects were identified on
      chromosomes 4 (D4Mit150) and x (DXMit249) in male mice, and on chromosome 9
      (D9Mit77) and 17 (D17Mit81) in female mice. A strong interaction between Nramp1
      and the major histocompatibility locus was also noted in female mice. The mapped
      loci may act as modifiers of Nramp1 action, and constitute novel entry points for
      the parallel search of loci regulating susceptibility to mycobacterial infections
      in humans.

PMID- 17024128
TI  - Repeated cycles of Clostridium-directed enzyme prodrug therapy result in
      sustained antitumour effects in vivo.
AB  - The unique properties of the tumour microenvironment can be exploited by using
      recombinant anaerobic clostridial spores as highly selective gene delivery
      vectors. Although several recombinant Clostridium species have been generated
      during the past decade, their efficacy has been limited. Our goal was to
      substantially improve the prospects of clostridia as a gene delivery vector.
      Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their
      capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among
      the enzymes tested, one showed superior prodrug turnover characteristics. In
      addition, we established an efficient gene transfer procedure, based on
      conjugation, which allows for the first time genetic engineering of Clostridium
      strains with superior tumour colonisation properties with high success rates.
      This conjugation procedure was subsequently used to create a recombinant C.
      sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a
      clinical setting situation, we have tested the effect of multiple consecutive
      treatment cycles, with antibiotic bacterial clearance between cycles.
      Importantly, this regimen demonstrated that intravenously administered spores of
      NTR-recombinant C. sporogenes produced significant antitumour efficacy when
      combined with prodrug administration.

PMID- 17024130
TI  - Complexity in the host response to Salmonella Typhimurium infection in AcB and
      BcA recombinant congenic strains.
AB  - The host response to Salmonella infection is controlled by its genetic makeup.
      Using the mouse model of typhoid fever, several genes were found to influence the
      outcome of Salmonella infection, including Nramp1 (Slc11a1). In order to improve
      our knowledge of genetic determinants of the mouse response to acute Salmonella
      Typhimurium infection, we performed a systematic screening of a set of A/J and
      C57BL/6J recombinant congenic strains (RCS) for their resistance to infection.
      While we knew that the parental strains differ in their susceptibility to
      Salmonella because C57BL/6J mice carry a non-functional allele at Nramp1, we
      hypothesized that other genes would influence the response to Salmonella and
      segregate in the RCS. We identified several RCS that showed a non-expected
      phenotype given their known Nramp1 genotype proving that the response to
      Salmonella in A/J and C57BL/6J mice is complex. Based on these findings, we
      selected two RCS for generation of fully informative F2 crosses, (AcB61 x 129S6)
      and (AcB64 x DBA/2J). Genetic analyses performed on these crosses identified five
      novel Salmonella susceptibility QTL mapping to chromosomes 3 (Ity4), 2 (Ity5), 14
      (Ity6), 7 (Ity7) and 15 (Ity8). These results illustrate the genetic complexity
      associated with the mouse response to Salmonella Typhimurium.

PMID- 17024131
TI  - Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus
      erythematosus-prone (NZB x NZW) F1 mice.
AB  - The F(1) hybrid of autoimmune hemolytic anemia-prone NZB and nonautoimmune NZW
      strains of mice has been studied as a murine model of systemic lupus
      erythematosus. Both NZB and F(1) hybrid mice show age-dependent spontaneous
      activation of peripheral CD4(+) T cells as reflected by the elevated frequencies
      of CD4(+) T cells positive for CD69 early activation marker. Both strains also
      show age-dependent abnormal decrease of the frequencies of CD62L(+) naive CD4(+)
      T cells and/or NTA260(+) memory CD4(+) T cells in the spleen. We studied the
      multigenic control of these abnormal features of peripheral CD4(+) T cells in
      (NZB x NZW) F(1) x NZW backcross mice by quantitative trait loci mapping and by
      association rule analysis. The abnormally elevated frequencies of CD69(+)CD4(+) T
      cells and decreased frequencies of CD62L(+) naive and/or NTA260(+) memory CD4(+)
      T cells were under the common genetic control, in which the interaction between
      MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell
      activation) on chromosome 12, plays a major role. The allelic effects of these
      loci likely predispose CD4(+) T cells to the loss of self-tolerance, and are
      responsible for the accelerated autoimmune phenotypes of (NZB x NZW) F(1) hybrid
      mice.

PMID- 17024132
TI  - Body weight and weight change in relation to blood pressure in normotensive men.
AB  - We examined blood pressure (BP) in association with weight change since age 20,
      body mass index (BMI) at different ages and fat distribution in normotensive
      individuals using baseline survey data collected in the Shanghai Men's Health
      Study, an ongoing population-based prospective cohort study of Chinese men aged
      40-74 years. All anthropometric and BP measurements were performed by medical
      professionals. Included in this analysis were 25 619 men who had no prior history
      of hypertension, diabetes or cardiovascular disease, never took any
      antihypertensive medication and had both normal systolic BP (SBP) and diastolic
      BP (DBP) (<140/90 mm Hg). Both SBP and DBP increased linearly across the whole
      range of weight gain since age 20. The adjusted mean differences between the
      highest and the lowest quintiles of weight gain were 6.0 mm Hg (95% confidence
      interval (CI): 5.6, 6.5) for SBP and 3.9 (95% CI: 3.6, 4.2) for DBP. When
      accounting for BMI at age 20, the multivariate-adjusted odds ratio of
      prehypertension (SBP, 120-139 and/or DBP, 80-89 mm Hg) was 4.1 (95% CI: 3.7, 4.5;
      P for trend <0.0001) comparing the extreme quintiles of weight gain. Similar
      positive associations were also observed for BMI at age 40, current BMI,
      circumferences of the waist and hips and waist-to-hip ratio. In conclusion, these
      data suggest that weight gain since age 20 and elevated adiposity may contribute
      significantly to the rise in BP in normotensive individuals, emphasizing the
      importance of weight control throughout adulthood in preventing high BP.

PMID- 17024133
TI  - Increased arterial vascular tone during the night in patients with essential
      hypertension.
AB  - The time-dependent incidence of cardiovascular events points to an important role
      of chronobiology for arterial properties. To evaluate arterial properties in
      patients with essential hypertension, we assessed arterial vascular tone during
      sleep at night in patients with essential hypertension and normotensive control
      subjects. Vascular tone was continuously quantified by the reflective index
      obtained by non-invasive digital photoplethysmography and an algorithm for
      continuous, investigator-independent, automatic analysis of digital volume pulse.
      During the first half of the night, the reflective index was significantly higher
      in 31 patients with essential hypertension compared to 30 normotensive control
      subjects (30.0+/-0.2 vs 28.8+/-0.2; P=0.001). In patients with essential
      hypertension, the reflective index significantly increased from 30.0+/-0.2 in the
      first half (from 2301 to 0230) to 30.7+/-0.2 in the second half (from 0231 to
      0600) of the night (n=31; P=0.027). In normotensive control subjects the
      reflective index also significantly increased from 28.8+/-0.2 in the first half
      of the night to 30.2+/-0.2 in the second half of the night (n=30; P=0.001). An
      increase of the reflective index tone indicated systemic vasoconstriction as
      confirmed by cold pressure tests and a significant correlation between arterial
      vascular tone and sympathetic nerve activity measured by microneurography from
      the peroneal nerve. Photoplethysmographic determination of arterial vascular tone
      demonstrated a significant increase of systemic arterial vascular tone in
      patients with essential hypertension during the first half of the night compared
      to normotensive control subjects.

PMID- 17024134
TI  - Association analysis of endothelial nitric oxide synthase gene polymorphism with
      primary hypertension in a Singapore population.
AB  - Vascular endothelial cells produce nitric oxide (NO), which contributes to the
      regulation of blood pressure and regional blood flow. Endothelial nitric oxide
      synthase (eNOS) gene polymorphisms are associated with coronary artery disease,
      but their linkage with primary hypertension is controversial. A total of 103
      individuals with primary hypertension and 104 normotensive control subjects were
      studied in Singapore. The specific genotypes for G894T missense variant in exon
      7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and T-786C in
      the promoter were isolated using allele-specific gene amplification and
      restriction fragment length polymorphism to examine the association of genotype
      and allelic frequency in both groups. Logistic regression analysis was also used
      to detect the association between genotypes and hypertension. Five genotypes of
      intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was
      significantly associated with the hypertension group (P = 0.035), but
      disequilibrium of G894T and T-786C was absent between the two groups (P = 0.419
      and P = 0.227), respectively. The overall distribution of allelic frequency
      differed significantly between the two groups, with four-repeat allele (4A) of
      intron 4 more frequent in the normotensive group than the hypertensive group (P =
      0.019). Logistic regression analysis showed that intron 4 B/B genotype was
      significantly associated with systolic blood pressure of individuals with body
      mass index greater than 25 kg/m2 (P = 0.04). In conclusion, the eNOS 4 B/B
      genotype is a genetic susceptibility factor for primary hypertension in a
      Singapore population.

PMID- 17024135
TI  - The association between serum uric acid level and long-term incidence of
      hypertension: Population-based cohort study.
AB  - Increasing experimental evidence, including recently developed animal models
      support a causal role for uric acid in the development of hypertension. However,
      it is not clear whether serum uric acid levels are independently associated with
      the long-term incidence of hypertension. We examined the association between
      serum uric acid levels and 10-year incidence of hypertension in a population
      based cohort study based in Beaver Dam city and township, Wisconsin, US. We
      studied 2520 hypertension-free individuals (56.3% women, age: 43-84 years, 98%
      Caucasian) at the baseline examination (1988-1990). The main outcome of interest
      was hypertension (systolic blood pressure (BP) of 140 mm Hg or higher, diastolic
      BP 90 mm Hg or higher, or combination of self-reported high BP diagnosis and use
      of antihypertensive medications) incidence over 10 years among baseline
      normotensive individuals. Nine hundred and fifty-six individuals developed
      hypertension over a 10-year follow-up period. The relative risk (RR) (95%
      confidence intervals (CI)) of incident hypertension increased in a dose-dependent
      manner (P-trend < 0.05 in all models) with increasing uric acid quartiles.
      Multivariable RR (95% CI) comparing the highest quartile of serum uric acid (> or
      =390 micromol/l) to the lowest quartile (< or =260 micromol/l) was 1.65 (1.41
      1.93). This association persisted in subgroup analyses by categories of smoking,
      alcohol intake, body mass index, baseline blood pressure and estimated glomerular
      filtration rate (GFR). In conclusion, increasing quartiles of serum uric acid was
      associated with 10-year incidence of hypertension independent of smoking, alcohol
      intake and baseline kidney function suggesting an independent positive
      association between serum uric acid levels and hypertension development among
      community-dwelling older adults.

PMID- 17024136
TI  - The relation between serum level of amioterminal propeptide of type I procollagen
      and diastolic dysfunction in hypertensive patients without diabetes mellitus: A
      pilot study.

PMID- 17024137
TI  - Blood pressure in relation to serum thyrotropin: The Tromso study.
AB  - It appears to be an association between hypothyroidism and hypertension. However,
      the relation between thyroid function and blood pressure within the normal serum
      thyrotropin (TSH) range is uncertain. In the fifth Tromso study, which is a
      population-based health survey, serum TSH and blood pressure were measured. This
      gave us the opportunity to test the hypothesis of a relation between serum TSH
      and blood pressure within the normal serum TSH range. In all 5872 subjects (2623
      male subjects) not using blood pressure or thyroxine medication were included in
      the present study. Within the normal serum TSH range (0.20-4.00 mIU/l), there was
      a significant and positive relation between serum TSH and both systolic and
      diastolic blood pressure. Within this range, and adjusted for age, body mass
      index and smoking status, the systolic blood pressure was 1.4 mm Hg and the
      diastolic 1.6 mm Hg higher in male subjects in the highest versus those in the
      lowest serum TSH quartile. The corresponding differences in the female subjects
      were 4.0 and 2.7 mm Hg, respectively. When dividing this cohort in those with
      systolic (>160 mm Hg) and diastolic (>95 mm Hg) hypertension, serum TSH was
      higher in the hypertensive subjects, but the differences were only statistically
      significant for diastolic hypertension (serum TSH 1.88+/-0.82 versus 1.69+/-0.74
      mIU/l for male subjects, and 1.79+/-0.78 versus 1.63+/-0.75 mIU/l for female
      subjects, P < 0.05). In conclusion, there is a modest, but significant positive
      association between serum TSH and blood pressure within the normal serum TSH
      range.

PMID- 17024138
TI  - Association study of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms
      and essential hypertension in northern Han Chinese.

PMID- 17024139
TI  - Safety and efficacy of early amino acids in preterm <28 weeks gestation:
      prospective observational comparison.
AB  - OBJECTIVE: To assess the safety and efficacy of early amino acid (AA)
      administration in preterm neonates <28 weeks gestational age. STUDY DESIGN:
      Prospective data collection for 1 year for the late AA group (AA started at 12-30
      h) and for another year with practice change to early AA administration
      (immediately after stabilization). RESULTS: Time of initiation of AA differed
      (early group 4+/-3 h vs late group 20+/-6 h; P<0.001). There were no
      statistically significant differences in the incidence of clinically significant
      metabolic acidosis. Blood urea at 24 h was higher in the early AA group. No
      significant differences in growth rate or neonatal outcomes were identified. Days
      to regain birth weight and sepsis were lower in the early AA group. CONCLUSIONS:
      Early AA administration was not associated with any clinically significant
      adverse effects; it was associated with reduction in the incidence of sepsis and
      marginally effective in reducing time to regain birth weight.

PMID- 17024140
TI  - Effects of human milk fortifier on the antimicrobial properties of human milk.
AB  - OBJECTIVE: To evaluate the effects of addition of human milk (HM) fortifier and
      iron on the anti-infective properties of HM. STUDY DESIGN: HM samples were
      collected from 28 lactating mothers who delivered prematurely, within the first
      week of post-natal life. HM fortifier Eoprotin was used. The effects of this
      fortifier against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa
      and Candida albicans were evaluated using a filter paper method. The measurements
      were repeated with pure HM, fortified HM and iron-added HM. RESULTS: HM inhibited
      the growth of S. aureus, E. coli, P. aeruginosa and Candida. Addition of HM
      fortifier did not result in any significant difference on this effect. The
      addition of iron to HM reduced antimicrobial effect against all three bacteria
      and the Candida. CONCLUSION: Premature HM has strong antimicrobial activity and
      addition of the milk fortifier Eoprotin does not change this effect, but addition
      of iron reduces this antimicrobial activity.

PMID- 17024141
TI  - The cardiothoracic ratio in AGA and SGA very low birth weight newborn infants.
AB  - BACKGROUND: Cardiothoracic (CT) ratio is a common measurement used to assess
      heart size in chest radiographs of pediatric patients, but no recent studies have
      analyzed the standards for CT ratios in very low birth weight (VLBW) infants.
      OBJECTIVE: The aim of this study was to provide improved standards for CT ratios
      measured from chest radiographs of VLBW (<1500 g) infants, and to compare CT
      ratios between small for gestational age (SGA) and appropriate for gestational
      age (AGA) infants in this population. DESIGN/METHODS: Among VLBW infants admitted
      to the Jacobi Medical Center NICU from 2002 to 2004, CT ratios were calculated
      from anteroposterior supine chest radiographs taken of 54 VLBW infants (18 SGA
      and 36 AGA group-matched on the basis of birthweight and sex) during the first 24
      h of life. RESULTS: There were no significant differences between the two groups
      with respect to birthweight, sex, 1-min Apgar score, 5-min Apgar score,
      intubation status and degree of inspiration. Median GA of the SGA infants was
      significantly greater than the AGA infants (30 and 27 weeks, respectively;
      P<0.001). CT ratios among SGA infants were significantly larger than those among
      AGAs. Using the widest internal width of the bony thorax, the mean CT ratio among
      SGA and AGA infants was 0.523 and 0.479, respectively (P=0.00102). CONCLUSIONS:
      VLBW SGA infants have larger CT ratios than VLBW AGA infants, suggesting that
      existing standards for normal CT ratios may be inappropriate for use among SGA
      infants.

PMID- 17024142
TI  - Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic
      pregnancy.
AB  - OBJECTIVE: Offspring of diabetes patients may suffer from tissue iron deficiency.
      Erythrocyte zinc protoporphyrin/heme (ZnPP/H) ratios measure impaired iron
      status. The aim of the study was to examine whether cord ZnPP/H ratios were
      associated with pregnancy glycemic control. METHODS: ZnPP/H was measured in cord
      blood from 31 pregnancies with insulin-treated diabetes (diabetes group) and
      compared to population normal values. Maternal glycemic control was assessed by
      daily glucose log, glycosylated hemoglobin and birth weight. RESULTS: Median cord
      ZnPP/H was higher in the diabetes group than the population normal values (106
      (65.2 to 146.8) microM/M vs 68.2 (37.6 to 98.8) micro/M, P < 0.0001). Ratios were
      directly correlated to surrogates of control (glycosylated hemoglobin, P = 0.05,
      and birth weight, P < 0.04). Cord ZnPP/H ratios from pregnancies with pre
      existing and gestational diabetes were similar. CONCLUSION: Because cord ZnPP/H
      was higher in large offspring of diabetic pregnancy, it might identify greater
      iron utilization for fetal erythropoiesis.

PMID- 17024143
TI  - Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can
      result in a decrease in use of antibiotics and total neonatal intensive care unit
      length of stay.
AB  - OBJECTIVE: To retrospectively determine if a negative 16S ribosomal RNA (rRNA)
      polymerase chain reaction (PCR) (PCR(-)) could lead to a decrease in the number
      of antibiotic doses and neonatal intensive care unit (NICU) length of stay (LOS)
      for infants admitted to the NICU for presumed early-onset sepsis (EOS) with
      negative blood culture results (BC(-)). STUDY DESIGN: Analysis included 419
      infants, greater than 35 weeks gestational age, with PCR(-), BC(-) and LOS > 48
      h. Both the investigators and clinical care team were unaware of the PCR results.
      The actual number of antibiotic doses (AAD) administered was compared to an
      estimated number of antibiotics doses (EAD) that would have been given until PCR(
      ) results were available by 18 h. The number of antibiotic doses saved was
      calculated as (AAD-EAD). The actual NICU LOS in hours (aLOS) for a subset of
      infants who remained in the hospital primarily for antibiotic therapy was
      compared to an estimated LOS (eLOS) if infants with PCR(-) were discharged from
      the NICU when clinically stable. The number of hours saved was calculated as
      (aLOS-eLOS). RESULTS: Approximately eight antibiotic doses and 85 NICU hours per
      infant could be saved using PCR(-) results available at 18 h. CONCLUSIONS: Use of
      16S rRNA PCR could decrease the number of antibiotics doses and NICU LOS for
      infants admitted for EOS. This may facilitate: (1) earlier NICU discharge; (2)
      parental satisfaction; and (3) decreased health care costs.

PMID- 17024144
TI  - New insights into spontaneous intestinal perforation using a national data set
      (3): antenatal steroids have no adverse association with spontaneous intestinal
      perforation.
AB  - OBJECTIVE: To examine whether antenatal steroids (ANS), alone or with early
      indomethacin, are associated with spontaneous intestinal perforation (SIP). SIP
      is a known complication of concurrent post-natal administration of glucocorticoid
      and indomethacin in extremely low birth weight (ELBW) infants. STUDY DESIGN: A
      large de-identified national data set was retrospectively examined for infants
      with SIP without any report of other malformation or necrotizing entrocolitis. A
      control group was then derived matching for gender and birth weight (+/- 20 g).
      Pre- and post-natal variables were tested by both univariate and multivariate
      analysis to identify associations with SIP. RESULTS: From January 1996 to June
      2004, there were 2 27 711 discharges from Pediatrix neonatal intensive care unit
      sites. From this population 388 infants with SIP associated with ELBW were
      compared to matched controls. Infants with SIP were more likely to have received
      early indomethacin and to have received a combination of early indomethacin with
      post-natal glucocorticoids (P < 0.05 for both). When used alone (without
      subsequent indomethacin), ANS showed no association with SIP. When used in
      conjunction with indomethacin, ANS did not increase the rate of SIP beyond
      indomethacin alone. CONCLUSION: ELBW Infants that acquire SIP were more likely to
      have been exposed to early indomethacin and post-natal glucocorticoids. However,
      no association was found between SIP and ANS within a well-powered cohort.

PMID- 17024145
TI  - Making a diagnosis of androgen deficiency in adult men: what to do until all the
      facts are in?

PMID- 17024146
TI  - Does growth hormone therapy increase the risk of cancer?

PMID- 17024147
TI  - Growth hormone therapy does not induce cancer.

PMID- 17024148
TI  - Should annual measurement of the ankle-brachial index be routine practice in
      diabetes care?

PMID- 17024149
TI  - Does impaired secretion of gastric acid reduce absorption of levothyroxine?

PMID- 17024150
TI  - Is hyperglycemia important in acute stroke?

PMID- 17024151
TI  - How effective are processes of care for the treatment of diabetes?

PMID- 17024152
TI  - The prevalence and management of cardiorenal risk factors in patients with
      diabetic nephropathy.

PMID- 17024153
TI  - Management of diabetic dyslipidemia: doing the right thing.

PMID- 17024154
TI  - Management of resistant prolactinomas.
AB  - Resistance to dopamine agonists occurs in a subset of patients with prolactin
      secreting pituitary tumors. The resistance is mediated by loss of pituitary D2
      receptors and occurs in both microadenomas and macroadenomas. Cabergoline is the
      most effective dopamine agonist and tumors that do not respond to bromocriptine
      or quinagolide frequently respond to cabergoline. Treatment options include
      maximizing the dose of the dopamine agonist, changing agonists, trans-sphenoidal
      surgery and radiation therapy. The goal of therapy is to restore and maintain
      gonadal and neurologic function, and this might occur in the absence of a normal
      prolactin level or a significant change in tumor size. Trans-sphenoidal pituitary
      surgery should be reserved for patients who are intolerant of medical therapy, or
      in whom this has failed. Radiation therapy has a limited role in treatment of
      resistant prolactinomas and should be reserved for patients in whom medical and
      surgical therapy has failed.

PMID- 17024155
TI  - Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin
      modifications and transcription regulation.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome
      characterized by tumors of the parathyroid glands, the pancreatic islets, the
      pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid
      tumors, often at a young age. Causal to the syndrome are germline mutations of
      the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has
      enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The
      product of the MEN1 gene is the nuclear protein menin. Recent observations
      indicate several functions for menin in the regulation of transcription, serving
      either as a repressor or as an activator: menin interacts with the activator
      protein-1-family transcription factor JunD, changing it from an oncoprotein into
      a tumor-suppressor protein, putatively by recruitment of histone deacetylase
      complexes; menin maintains transforming growth factor beta mediated signal
      transduction involved in parathyroid hormone and prolactin gene expression; and
      menin is an integral component of histone methyltransferase complexes. In this
      capacity menin is a regulator of expression of the cyclin-dependent-kinase
      inhibitors p18INK4C and p27Kip1; furthermore, menin serves as a co-activator of
      estrogen receptor mediated transcription, by recruiting methyltransferase
      activity to lysine 4 of histone 3 at the estrogen responsive TFF1(pS2) gene
      promoter. We propose that menin links transcription-factor function to histone
      modification pathways and that this is crucial for MEN1 tumorigenesis.
      Understanding the molecular pathology of MEN1 tumorigenesis will lead to new
      therapeutic strategies.

PMID- 17024156
TI  - Drug Insight: prolactin-receptor antagonists, a novel approach to treatment of
      unresolved systemic and local hyperprolactinemia?
AB  - Prolactin is a polypeptide hormone whose major biological actions are related to
      normal lactation and reproduction. Abnormally high prolactin levels, referred to
      as hyperprolactinemia, can result in various reproductive disorders. Currently,
      therapeutic management of hyperprolactinemia relies on dopamine agonists, since
      dopamine is the primary physiological suppressor of pituitary prolactin
      production. Epidemiologic studies have shown that prolactin levels in the high
      normal range, as well as medications that interfere with dopamine action (e.g.
      certain antipsychotic drugs), might correlate with increased breast cancer risk.
      In addition to circulating prolactin, it is now well established that prolactin
      is also produced locally within various tissues, including breast and prostate.
      Increasing evidence, mainly from animal studies at present, suggests that excess
      locally produced prolactin may promote the growth of breast and prostate tumors
      via an autocrine or paracrine mechanism. These findings have renewed the interest
      in finding alternative strategies to suppress prolactin actions when dopamine
      agonists are ineffective. Our studies of the relationship between prolactin
      structure and function have resulted in the development of pure prolactin
      receptor antagonists. These molecules prevent endogenous prolactin from exerting
      its actions via a competitive mechanism for receptor binding. In this review, we
      discuss the possible future therapeutic utility of this novel class of compounds.

PMID- 17024157
TI  - Acromegaly diagnosed in a young woman presenting with headache and arthritis.
AB  - BACKGROUND: A 38-year-old woman presented with severe headaches to her primary
      care physician. The patient had been diagnosed with rheumatoid arthritis and had
      begun having headache 4 years previously. An MRI scan revealed an 11-12 mm
      pituitary tumor. Her physical examination was unremarkable for the classic acral
      or facial changes characteristic of acromegaly, and she was referred for
      neuroendocrine consultation for a presumed nonfunctioning adenoma.
      INVESTIGATIONS: MRI of the pituitary, and laboratory investigations that included
      measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels.
      DIAGNOSIS: In view of the elevated level of IGF1 and presence of a pituitary
      adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma
      that secretes growth hormone. MANAGEMENT: The patient underwent trans-sphenoidal
      surgery, which resulted in resolution of joint pain and headache, eradication of
      the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone
      (confirmed by oral glucose tolerance test postoperatively).

PMID- 17024159
TI  - Nephrologists sans frontieres: On the metamorphosis of turning into a fly
      geneticist.

PMID- 17024160
TI  - An alcoholic patient with recurrent renal failure and proteinuria.

PMID- 17024161
TI  - Recurrence of abdominal pain in a peritoneal dialysis patient after treatment of
      peritonitis.

PMID- 17024162
TI  - Regulation of ENaCs by proteases: An increasingly complex story.
AB  - Proteolytic processing of epithelial Na+ channel (ENaC) subunits has an important
      role in the regulation of ENaC gating. This Commentary addresses the potential
      roles of specific proteases and protease inhibitors in the control of Na+ channel
      gating.

PMID- 17024163
TI  - Is there a need to optimize glycemic control in hemodialyzed diabetic patients?
AB  - The report of Williams et al. gives rise to at least two important questions
      regarding diabetic patients on maintenance hemodialysis: (1) Does glycemic
      control play a significant role? (2) Is HbA1c a reliable measure of glycemic
      control? These questions are discussed. It is recommended that you treat ESRD
      patients with diabetes according to guidelines given for patients without ESRD.

PMID- 17024166
TI  - Do advanced glycation end products and glucose induce similar signaling events in
      mesangial cells?

PMID- 17024168
TI  - Mortality risk for patients receiving hemodiafiltration versus hemodialysis.

PMID- 17024169
TI  - Cardiac troponins and chronic kidney disease.

PMID- 17024171
TI  - Cholesterol crystal embolism: Diagnostic and treatment.

PMID- 17024173
TI  - Differences between type I and II membranoproliferative glomerulonephritis.

PMID- 17024175
TI  - Oxidative modification of M-type K(+) channels as a mechanism of cytoprotective
      neuronal silencing.
AB  - Voltage-gated K(+) channels of the Kv7 family underlie the neuronal M current
      that regulates action potential firing. Suppression of M current increases
      excitability and its enhancement can silence neurons. We here show that three of
      five Kv7 channels undergo strong enhancement of their activity by oxidative
      modification induced by physiological concentrations of hydrogen peroxide. A
      triple cysteine pocket in the channel S2-S3 linker is critical for this effect.
      Oxidation-induced enhancement of M current produced a hyperpolarization and a
      dramatic reduction of action potential firing frequency in rat sympathetic
      neurons. As hydrogen peroxide is robustly produced during hypoxia-induced
      oxidative stress, we used an oxygen/glucose deprivation neurodegeneration model
      that showed neuronal death to be severely accelerated by M current blockade. Such
      blockade had no effect on survival of normoxic neurons. This work describes a
      novel pathway of M-channel regulation and suggests a role for M channels in
      protective neuronal silencing during oxidative stress.

PMID- 17024176
TI  - A novel HSF1-mediated death pathway that is suppressed by heat shock proteins.
AB  - Heat shock response is an adoptive response to proteotoxic stress, and a major
      heat shock transcription factor 1 (HSF1) has been believed to protect cells from
      cell death by inducing heat shock proteins (Hsps) that assist protein folding and
      prevent protein denaturation. However, it is revealed recently that HSF1 also
      promotes cell death of male germ cells. Here, we found a proapoptotic Tdag51 (T
      cell death associated gene 51) gene as a direct target gene of HSF1. Heat shock
      and other stresses induced different levels of Hsps and Tdag51, which depend on
      cell types. Hsps bound directly to the N-terminal pleckstrin-homology like (PHL)
      domain of Tdag51, and suppressed death activity of the C-terminal
      proline/glutamine/histidine-rich domain. Tdag51, but not major Hsps, were induced
      in male germ cells exposed to high temperatures. Analysis of Tdag51-null testes
      showed that Tdag51 played substantial roles in promoting heat shock-induced cell
      death in vivo. These data suggest that cell fate on proteotoxic condition is
      determined at least by balance between Hsp and Tdag51 levels, which are
      differently regulated by HSF1.

PMID- 17024177
TI  - The phosphorylation status of PAS-B distinguishes HIF-1alpha from HIF-2alpha in
      NBS1 repression.
AB  - Hypoxia promotes genetic instability for tumor progression. Recent evidence
      indicates that the transcription factor HIF-1alpha impairs DNA mismatch repair,
      yet the role of HIF-1alpha isoform, HIF-2alpha, in tumor progression remains
      obscure. In pursuit of the involvement of HIF-alpha in chromosomal instability,
      we report here that HIF-1alpha, specifically its PAS-B, induces DNA double-strand
      breaks at least in part by repressing the expression of NBS1, a crucial DNA
      repair gene constituting the MRE11A-RAD50-NBS1 complex. Despite strong
      similarities between the two isoforms, HIF-2alpha fails to do so. We demonstrate
      that this functional distinction stems from phosphorylation of HIF-2alpha Thr-324
      by protein kinase D1, which discriminates between subtle differences of the two
      PAS-B in amino-acid sequence, thereby precluding NBS1 repression. Hence, our
      findings delineate a molecular pathway that functionally distinguishes HIF-1alpha
      from HIF-2alpha, and arguing a unique role for HIF-1alpha in tumor progression by
      promoting genomic instability.

PMID- 17024178
TI  - A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus.
AB  - In (+) RNA coronaviruses, replication and transcription of the giant
      approximately 30 kb genome to produce genome- and subgenome-size RNAs of both
      polarities are mediated by a cognate membrane-bound enzymatic complex. Its RNA
      dependent RNA polymerase (RdRp) activity appears to be supplied by non-structural
      protein 12 (nsp12) that includes an RdRp domain conserved in all RNA viruses.
      Using SARS coronavirus, we now show that coronaviruses uniquely encode a second
      RdRp residing in nsp8. This protein strongly prefers the internal 5'-(G/U)CC-3'
      trinucleotides on RNA templates to initiate the synthesis of complementary
      oligonucleotides of <6 residues in a reaction whose fidelity is relatively low.
      Distant structural homology between the C-terminal domain of nsp8 and the
      catalytic palm subdomain of RdRps of RNA viruses suggests a common origin of the
      two coronavirus RdRps, which however may have evolved different sets of catalytic
      residues. A parallel between the nsp8 RdRp and cellular DNA-dependent RNA
      primases is drawn to propose that the nsp8 RdRp produces primers utilized by the
      primer-dependent nsp12 RdRp.

PMID- 17024179
TI  - Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90.
AB  - Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a component of viral
      replicase and is well known to modulate the functions of several host proteins.
      Here, we show that NS5A specifically interacts with FKBP8, a member of the FK506
      binding protein family, but not with other homologous immunophilins. Three sets
      of tetratricopeptide repeats in FKBP8 are responsible for interactions with NS5A.
      The siRNA-mediated knockdown of FKBP8 in a human hepatoma cell line harboring an
      HCV RNA replicon suppressed HCV RNA replication, and this reduction was reversed
      by the expression of an siRNA-resistant FKBP8 mutant. Furthermore,
      immunoprecipitation analyses revealed that FKBP8 forms a complex with Hsp90 and
      NS5A. Treatment of HCV replicon cells with geldanamycin, an inhibitor of Hsp90,
      suppressed RNA replication in a dose-dependent manner. These results suggest that
      the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV
      RNA replication.

PMID- 17024180
TI  - Receptor specific downregulation of cytokine signaling by autophosphorylation in
      the FERM domain of Jak2.
AB  - The tyrosine kinase, Janus kinase-2 (Jak2), plays a pivotal role in signal
      transduction through a variety of cytokine receptors, including the receptor for
      erythropoietin (Epo). Although the physiological relevance of Jak2 has been
      definitively established, less is known about its regulation. In studies
      assessing the roles of sites of tyrosine phosphorylation, we identified Y(119) in
      the FERM (band 4.1, Ezrin, radixin and moesin) domain as a phosphorylation site.
      In these studies, we demonstrate that the phosphorylation of Y(119) in response
      to Epo downregulates Jak2 kinase activity. Using a phosphorylation mimic mutation
      (Y(119)E), downregulation is shown to involve dissociation of Jak2 from the
      receptor complex. Conversely, a Y(119)F mutant is more stably associated with the
      receptor complex. Thus, in cytokine responses, ligand binding induces activation
      of receptor associated Jak2, autophosphorylation of Y(119) in the FERM domain and
      the subsequent dissociation of the activated Jak2 from the receptor and
      degradation. This regulation occurs with the receptors for Epo, thrombopoietin
      and growth hormone but not with the receptor for interferon-gamma.

PMID- 17024181
TI  - Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and
      present peptidoglycan to PGRP-SA.
AB  - Genetic evidence indicates that Drosophila defense against Gram-positive bacteria
      is mediated by two putative pattern recognition receptors acting upstream of
      Toll, namely Gram-negative binding protein 1 (GNBP1) and peptidoglycan
      recognition protein SA (PGRP-SA). Until now however, the molecular recognition
      proceedings for sensing of Gram-positive pathogens were not known. In the
      present, we report the physical interaction between GNBP1 and PGRP-SA using
      recombinant proteins. GNBP1 was able to hydrolyze Gram-positive peptidoglycan
      (PG), while PGRP-SA bound highly purified PG fragments (muropeptides).
      Interaction between these proteins was enhanced in the presence of PG or
      muropeptides. PGRP-SA binding depended on the polymerization status of the
      muropeptides, pointing to constraints in the number of PGRP-SA molecules bound
      for signaling initiation. We propose a model whereby GNBP1 presents a processed
      form of PG for sensing by PGRP-SA and that a tripartite interaction between these
      proteins and PG is essential for downstream signaling.

PMID- 17024182
TI  - EBP1 regulates organ size through cell growth and proliferation in plants.
AB  - Plant organ size shows remarkable uniformity within species indicating strong
      endogenous control. We have identified a plant growth regulatory gene,
      functionally and structurally homologous to human EBP1. Plant EBP1 levels are
      tightly regulated; gene expression is highest in developing organs and correlates
      with genes involved in ribosome biogenesis and function. EBP1 protein is
      stabilised by auxin. Elevating or decreasing EBP1 levels in transgenic plants
      results in a dose-dependent increase or reduction in organ growth, respectively.
      During early stages of organ development, EBP1 promotes cell proliferation,
      influences cell-size threshold for division and shortens the period of
      meristematic activity. In postmitotic cells, it enhances cell expansion. EBP1 is
      required for expression of cell cycle genes; CyclinD3;1, ribonucleotide reductase
      2 and the cyclin-dependent kinase B1;1. The regulation of these genes by EBP1 is
      dose and auxin dependent and might rely on the effect of EBP1 to reduce RBR1
      protein level. We argue that EBP1 is a conserved, dose-dependent regulator of
      cell growth that is connected to meristematic competence and cell proliferation
      via regulation of RBR1 level.

PMID- 17024183
TI  - Evidence for transmembrane proton transfer in a dihaem-containing membrane
      protein complex.
AB  - Membrane protein complexes can support both the generation and utilisation of a
      transmembrane electrochemical proton potential ('proton-motive force'), either by
      transmembrane electron transfer coupled to protolytic reactions on opposite sides
      of the membrane or by transmembrane proton transfer. Here we provide the first
      evidence that both of these mechanisms are combined in the case of a specific
      respiratory membrane protein complex, the dihaem-containing quinol:fumarate
      reductase (QFR) of Wolinella succinogenes, so as to facilitate transmembrane
      electron transfer by transmembrane proton transfer. We also demonstrate the non
      functionality of this novel transmembrane proton transfer pathway ('E-pathway')
      in a variant QFR where a key glutamate residue has been replaced. The 'E
      pathway', discussed on the basis of the 1.78-Angstrom-resolution crystal
      structure of QFR, can be concluded to be essential also for the viability of
      pathogenic epsilon-proteobacteria such as Helicobacter pylori and is possibly
      relevant to proton transfer in other dihaem-containing membrane proteins,
      performing very different physiological functions.

PMID- 17024184
TI  - Differential contribution of Puma and Noxa in dual regulation of p53-mediated
      apoptotic pathways.
AB  - The activation of tumor suppressor p53 induces apoptosis or cell cycle arrest
      depending on the state and type of cell, but it is not fully understood how these
      different responses are regulated. Here, we show that Puma and Noxa, the well
      known p53-inducible proapoptotic members of the Bcl-2 family, differentially
      participate in dual pathways of the induction of apoptosis. In normal cells, Puma
      but not Noxa induces mitochondrial outer membrane permeabilization (MOMP), and
      this function is mediated in part by a pathway that involves calcium release from
      the endoplasmic reticulum (ER) and the subsequent caspase activation. However,
      upon E1A oncoprotein expression, cells also become susceptible to MOMP induction
      by Noxa, owing to their sensitization to the ER-independent pathway. These
      findings offer a new insight into differential cellular responses induced by p53,
      and may have therapeutic implications in cancer.

PMID- 17024185
TI  - Dynein-mediated pulling forces drive rapid mitotic spindle elongation in Ustilago
      maydis.
AB  - Spindle elongation segregates chromosomes and occurs in anaphase, an essential
      step in mitosis. Dynein-mediated pulling forces position the spindle, but their
      role in anaphase is a matter of debate. Here, we demonstrate that dynein is
      responsible for rapid spindle elongation in the model fungus Ustilago maydis. We
      show that initial slow elongation is supported by kinesin-5, which is located in
      the spindle mid-zone. When the spindle reaches approximately 2 microm in length,
      the elongation rate increases four-fold. This coincides with the appearance of
      long and less-dynamic microtubules (MTs) at each pole that accumulate dynein at
      their tips. Laser-mediated nanosurgery revealed that these MTs exert pulling
      forces in control cells, but not in dynein mutants. In addition, dynein mutants
      undergo initial slow anaphase, but fail to establish less-dynamic MTs and do not
      perform rapid spindle elongation, suggesting that dynein drives anaphase B. This
      is most likely mediated by cortical sliding of astral MTs along stationary
      dynein, which is off-loaded from the MT plus-end to the cortex.

PMID- 17024186
TI  - An interaction between U2AF 65 and CF I(m) links the splicing and 3' end
      processing machineries.
AB  - The protein factor U2 snRNP Auxiliary Factor (U2AF) 65 is an essential component
      required for splicing and involved in the coupling of splicing and 3' end
      processing of vertebrate pre-mRNAs. Here we have addressed the mechanisms by
      which U2AF 65 stimulates pre-mRNA 3' end processing. We identify an
      arginine/serine-rich region of U2AF 65 that mediates an interaction with an RS
      like alternating charge domain of the 59 kDa subunit of the human cleavage factor
      I (CF I(m)), an essential 3' processing factor that functions at an early step in
      the recognition of the 3' end processing signal. Tethered functional analysis
      shows that the U2AF 65/CF I(m) 59 interaction stimulates in vitro 3' end cleavage
      and polyadenylation. These results therefore uncover a direct role of the U2AF
      65/CF I(m) 59 interaction in the functional coordination of splicing and 3' end
      processing.

PMID- 17024187
TI  - A PI3K activity-independent function of p85 regulatory subunit in control of
      mammalian cytokinesis.
AB  - Cytosolic division in mitotic cells involves the function of a number of
      cytoskeletal proteins, whose coordination in the spatio-temporal control of
      cytokinesis is poorly defined. We studied the role of p85/p110 phosphoinositide
      kinase (PI3K) in mammalian cytokinesis. Deletion of the p85alpha regulatory
      subunit induced cell accumulation in telophase and appearance of binucleated
      cells, whereas inhibition of PI3K activity did not affect cytokinesis. Moreover,
      reconstitution of p85alpha-deficient cells with a Deltap85alpha mutant, which
      does not bind the catalytic subunit, corrected the cytokinesis defects of
      p85alpha(-/-) cells. We analyzed the mechanism by which p85alpha regulates
      cytokinesis; p85alpha deletion reduced Cdc42 activation in the cleavage furrow
      and septin 2 accumulation at this site. As Cdc42 deletion also triggered septin 2
      and cytokinesis defects, a mechanism by which p85 controls cytokinesis is by
      regulating the local activation of Cdc42 in the cleavage furrow and in turn
      septin 2 localization. We show that p85 acts as a scaffold to bind Cdc42 and
      septin 2 simultaneously. p85 is thus involved in the spatial control of cytosolic
      division through regulation of Cdc42 and septin 2, in a PI3K-activity independent
      manner.

PMID- 17024189
TI  - Growing pains.
AB  - Spain's backing of biomedical research has grown steadily over the past few
      years, but the direction of some of its key programs could turn this support into
      a wasted opportunity.

PMID- 17024188
TI  - CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and translational
      control of AMPA receptor GluR2 mRNA.
AB  - CPEB is a sequence-specific RNA-binding protein that promotes polyadenylation
      induced translation in oocytes and neurons. Vertebrates contain three additional
      genes that encode CPEB-like proteins, all of which are expressed in the brain.
      Here, we use SELEX, RNA structure probing, and RNA footprinting to show that CPEB
      and the CPEB-like proteins interact with different RNA sequences and thus
      constitute different classes of RNA-binding proteins. In transfected neurons,
      CPEB3 represses the translation of a reporter RNA in tethered function assays; in
      response to NMDA receptor activation, translation is stimulated. In contrast to
      CPEB, CPEB3-mediated translation is unlikely to involve cytoplasmic
      polyadenylation, as it requires neither the cis-acting AAUAAA nor the trans
      acting cleavage and polyadenylation specificity factor, both of which are
      necessary for CPEB-induced polyadenylation. One target of CPEB3-mediated
      translation is GluR2 mRNA; not only does CPEB3 bind this RNA in vitro and in
      vivo, but an RNAi knockdown of CPEB3 in neurons results in elevated levels of
      GluR2 protein. These results indicate that CPEB3 is a sequence-specific
      translational regulatory protein.

PMID- 17024191
TI  - WHO's next?

PMID- 17024192
TI  - Medical students protest perks from drug companies.

PMID- 17024193
TI  - Spain's ill-conceived project leaves its scientists in the lurch.

PMID- 17024194
TI  - Profile. Stephen Lewis.

PMID- 17024196
TI  - Crime and punishment.

PMID- 17024197
TI  - Complement targeting of nonhuman sialic acid does not mediate cell death of human
      embryonic stem cells.

PMID- 17024200
TI  - Controlling angiogenesis in heart valves.

PMID- 17024201
TI  - Multiple sclerosis: putting two and two together.

PMID- 17024202
TI  - Alzheimer disease: presenilin springs a leak.

PMID- 17024203
TI  - Alzheimer disease: BACE1 branches out.

PMID- 17024204
TI  - Defeating T-cell fatigue in HIV.

PMID- 17024205
TI  - Targeted cancer treatment: resisting arrest.

PMID- 17024207
TI  - Venture science: climbing the ladder to telomerase, cognitive therapy and in situ
      hybridization.

PMID- 17024208
TI  - Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human
      cancer and aging.

PMID- 17024209
TI  - How an anomalous finding led to a new system of psychotherapy.

PMID- 17024210
TI  - Through the looking glass.

PMID- 17024213
TI  - Rapid and reliable genotyping of polymorphic loci modifying correct splicing of
      CFTR pre-mRNA using mass spectrometry.
AB  - We describe a fast and unambiguous method for haplotyping the (TG)mTn repeat in
      IVS8 and determining three other single nucleotide polymorphisms (SNPs) in exons
      10, 14a and 24 in the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene affecting correct splicing of the CFTR pre-mRNA using primer extension and
      mass spectrometry. The diagnostic products are generated by primer extension
      (PEX) reactions, which require a single detection primer complementary to a
      region downstream of a target strand's variable site. On addition of a polymerase
      and an appropriate mixture of dNTP's and 2', 3'-dideoxynucleotide triphosphates
      (ddNTP's), the primer is extended through the mutation region until the first
      ddNTP is incorporated and the mass of the extension products determines the
      composition of the variable site. Analysis of patient DNA assigned the correct
      and unambiguous haplotype for the (TG)mTn repeat in intron 8 of the CFTR gene.
      Additional crucial SNPs influencing correct splicing in exon 10, 14 and 24 can
      easily be detected by biplexing the assay to genotype allelic variants important
      for correct splicing of the CFTR pre-mRNA. Different PEX reactions with
      subsequent mass spectrometry generate sufficient data, to enable unambiguous and
      easy haplotyping of the (TG)mTn repeat in the CFTR gene. The method can be easily
      extended to the inclusion of additional SNPs of interest by biplexing some of the
      PEX reactions. All experimental steps required for PEX are amenable to the high
      degree of automation desirable for a high-throughput diagnostic setting,
      facilitating the work of clinicians involved in the diagnosis of non-classic
      cystic fibrosis.

PMID- 17024214
TI  - Towards mapping phenotypical traits in 18p- syndrome by array-based comparative
      genomic hybridisation and fluorescent in situ hybridisation.
AB  - Molecular karyotyping holds the promise of improving genotype-phenotype
      correlations for frequent chromosome conditions such as the 18p- syndrome. In
      spite of more than 150 reported cases with deletions in 18p, no reliable
      phenotype map for the characteristic clinical findings such as mental
      retardation, post-natal growth retardation and typical facial features has been
      established yet. Here, we report on four patients with partial monosomy 18p of
      different sizes owing to unbalanced translocations that were thoroughly
      characterised clinically and by molecular karyotyping. One patient had a terminal
      deletion of 1.6 Mb in 18p and a trisomy of 8q24.23-qter as determined by array
      based comparative genomic hybridisation and large insert clone fluorescent in
      situ hybridisation. In two sibs and a fourth patient, cytogenetic and molecular
      cytogenetic analyses showed the terminal deletions in 18p (8.0 and 13.84 Mb,
      respectively) to be accompanied by partial trisomies of 20p. Literature analyses
      of typical phenotypic features of 18p-, 8q+ and 20p+ syndromes allowed the
      attribution of clinical findings in our patients to the respective chromosomal
      aberration. Based on these data, we propose a phenotype map for several clinical
      features of the 18p- syndrome: Round face was tentatively mapped to the distal
      1.6 Mb of 18p; post-natal growth retardation and seizures to the distal 8 Mb and
      ptosis and short neck to the proximal half of 18p.

PMID- 17024216
TI  - Uveitis and Fabry disease.

PMID- 17024217
TI  - Management of symptomatic choroidal naevi with photodynamic therapy.
AB  - BACKGROUND/AIMS: To describe the use of photodynamic therapy (PDT) in the
      management of symptomatic serous retinal detachment associated with choroidal
      naevi. METHODS: Interventional case series. The records of seven patients with
      choroidal naevus and associated serous retinal detachment, treated with PDT were
      reviewed retrospectively. Main outcome measures were Snellen visual acuity,
      clinical appearance, and ocular tomographic findings. RESULTS: All seven patients
      showed a reduction in the degree of serous detachment and symptomatic
      improvement. Five patients showed a corresponding improvement in visual acuity
      that persisted over a mean period of 9 months. CONCLUSION: PDT appears to be
      effective in the management of serous retinal detachment associated with
      choroidal naevus.

PMID- 17024218
TI  - Ptosis caused by orbicularis myokymia and treated with botulinum toxin: a case
      report.

PMID- 17024219
TI  - Can we predict which patients are at risk of having an ungradeable digital image
      for screening for diabetic retinopathy?
AB  - PURPOSE: We aimed to determine the reasons for, and variables which predicted,
      ungradeable retinal photographs during screening patients for diabetic
      retinopathy. MATERIALS AND METHODS: Age, duration of diabetes, visual acuity, and
      HbA1c were recorded. Following dark adaptation, a single 45 degrees nonmydriatic
      photograph was taken of each fundus. The pupils were then dilated and the
      photograph repeated. Using slit lamp biomicroscopy, lenticular changes (LOCS
      III), and fundus appearance were recorded. RESULTS: In ungradeable photographs
      the fovea could not be visualised in 98% of cases of images from nonmydriatic
      photography, and in 88% if mydriasis was used. Poor definition in the
      nonmydriatic image was associated with a subsequent ungradeable mydriatic
      photograph (P=0.001), however, the positive predictive value was poor (34%). Age,
      posterior subcapsular cataract, and near vision predicted ungradeable status of
      nonmydriatic photographs (P<0.001, P=0.004, P=0.006, respectively; regression
      analysis). Nuclear colour and poor definition of the nonmydriatic photograph
      predicted ungradeable status of mydriatic photographs (P=0.006 & P=0.001,
      respectively). CONCLUSION: Inability to visualise the fovea is the commonest
      cause of an ungradeable image from digital retinal photography. Age and posterior
      subcapsular cataract were best predictors of ungradeable status of nonmydriatic
      fundus photographs. Nuclear colour was the strongest predictor for ungradeable
      mydriatic photography.

PMID- 17024220
TI  - The -174G/C interleukin-6 promoter polymorphism influences the development of
      macular oedema following uncomplicated phacoemulsification surgery.
AB  - AIM: To determine whether the functional -174 G/C interleukin-6 gene polymorphism
      is a risk factor for the development of cystoid macular oedema (CMO) following
      routine uncomplicated phacoemulsification surgery in patients with no established
      risk factors. METHODS: A total of 40 patients who underwent routine
      phacoemulsification surgery as part of a randomised controlled trial comparing
      the use of postoperative steroid drops against a single sub-tenon injection of
      triamcinolone were genotyped for the IL-6 -174G/C polymorphism. All patients
      underwent fluorescein angiography at 30 days and anterior chamber flare
      measurements pre-operatively and at day 1, 7, and 30. RESULTS: Angiographic CMO
      developed in 14 patients of the 40 studied. 9 out of the 14 patients carried the
      GG genotype (Fisher's exact test P=0.05, Hazard ratio for GG genotype; 4.05 (1.02
      16.00)). There was no difference in flare measurements between the GG and Non-GG
      (GC/CC) group. The two groups were otherwise well matched in terms of age, sex,
      phacoemulsification energy used intraoperatively, and proportion of patients
      receiving postoperative triamcinolone or steroid drops. CONCLUSION: The -174G/C
      interleukin-6 promoter gene variant appears to modulate the response to
      phacoemulsification surgery and to influence the development of postoperative
      CMO. These data suggest a genetic predisposition to this complication.

PMID- 17024221
TI  - Risk factors for cystoid macular oedema in patients with uveitis.
AB  - PURPOSE: To determine ophthalmologic and systemic factors associated with the
      presence of cystoid macular oedema (CMO) in patients with uveitis. METHODS:
      Retrospective cross-sectional study in which 97 consecutive patients with uveitis
      filled in an extensive questionnaire for the presence of cardiovascular diseases
      and its risk factors. An analysis of the ophthalmologic and questionnaire data
      was conducted. RESULTS: CMO was present in 44% (43/97) of patients. Its presence
      was strongly associated with increasing age (P=0.001) and age at onset of uveitis
      (P<0.001). For patients older than 50 years, the risk of having CMO was 3.8-fold
      (95% confidence intervals 1.6-9.0) larger than for younger patients. The most
      frequent anatomic location of uveitis associated with CMO was panuveitis (49%).
      Papillary leakage on fluorescein angiography was associated with CMO (P<0.001),
      independently of other risk factors. After adjustment for age, multivariate
      logistic regression showed no association between cardiovascular disease and its
      risk factors and the presence of CMO. CONCLUSIONS: Age, independent of duration
      of uveitis, was a major risk factor for the presence of CMO in uveitis. A
      positive correlation between CMO and papillary leakage on angiography was noted.

PMID- 17024222
TI  - A hazard of undiagnosed diabetes with benign prostatic hyperplasia: bilateral
      endogenous bacterial endophthalmitis.

PMID- 17024223
TI  - Preliminary evaluation of nonpenetrating deep sclerectomy with autologous scleral
      implant in open-angle glaucoma.
AB  - AIM: The aim of this study is to evaluate the short-term result of the use of an
      autologous scleral implant during the nonpenetrating deep sclerectomy operation
      instead of the more expensive collagen implant. DESIGN: Prospective nonrandomized
      pilot study. PATIENTS AND METHODS: This study included 20 eyes of 20 patients
      with a mean age of 42.3+/-8.1 years and the mean of preoperative best-corrected
      visual acuity was 0.66+/-6.2. All patients were indicated for conventional deep
      sclerectomy operation but with implantation of an autologous scleral implant. The
      operation was considered completely successful if the intraocular pressure (IOP)
      is below 18 mmHg without medications while qualified success was considered if
      the IOP was below 18 mmHg with medications. RESULTS: This technique succeeded in
      declining the mean IOP from 33.1+/-6.2 mmHg preoperatively to 14.6+/-3.8 mmHg
      postoperatively by the end of the follow-up period (12 months). Complete and
      qualified successful results were seen in 85% of cases. Nd:YAG goniopuncture was
      needed in 45% of the cases. This intervention was needed 14.0+/-10.0 weeks
      postoperatively. The study group showed low incidence of postoperative
      complication with statistically nonsignificant effect on the postoperative visual
      acuity. CONCLUSION: The use of autologous scleral implant can be of value in
      controlling the IOP with low cost to the patient. Nd:YAG goniopuncture is to be
      performed around the third month postoperatively in cases with advanced
      glaucomatous changes to avoid the problem of early implant induced fibrosis.
      Further long-term comparative study on wider scale is needed to detect the exact
      value of this technique and to evaluate its long-term result.

PMID- 17024224
TI  - Intraocular pressure before and after visual field examination.
AB  - PURPOSE: To evaluate the influence of visual field (VF) examinations using modern
      techniques with short examination times on the intraocular pressure (IOP).
      METHODS: Sixty-one consecutive patients, aged 28-90 years, 40 women and 21 men,
      were examined. Forty patients were treated for glaucoma and 21 were untreated
      patients with ocular hypertension or suspected glaucoma. Twenty-one subjects were
      examined using the Humphrey Field Analyzer, using SITA programs, and 40 with high
      pass resolution perimetry (HRP). Goldmann applanation tonometry was performed
      immediately before and after the VF examinations. RESULTS: A difference in IOP of
      more than 2 mm Hg before and after the VF examination was observed in 14 of the
      61 patients (23%). The maximum change in each direction was 4 mm Hg. The mean
      differences were not significant. All eight subjects with increasing IOP after VF
      examinations were examined using the HRP technique (P=0.04). CONCLUSION: Modern
      VF techniques with short examination time do not seem to significantly influence
      IOP.

PMID- 17024225
TI  - Syphilitic acute posterior placoid chorioretinitis in nonimmuno-compromised
      patients.
AB  - PURPOSE: To describe the clinical and angiographic features of three cases of
      secondary syphilis in immunocompetent patients, which presented as acute
      posterior placoid chorioretinitis (APPC) to the ophthalmologist. METHODS:
      Interventional case series. The aetiology of the APPC was confirmed by serology
      to be secondary syphilis. Optical coherence tomography, electrophysiology, fundus
      fluorescein, and indocyanine green (ICG) angiography were performed at
      presentation and after resolution. Appropriate treatment for secondary syphilis
      was instituted in each patient. RESULTS: The clinical features, fundus
      fluorescein and ICG angiography, multifocal electroretinography (mfERG), and
      optical coherence tomography findings of APPC are described. All three patients
      had a satisfactory resolution of the APPC with improvement in visual acuity.
      CONCLUSIONS: APPC in secondary syphilis can occur even in immunocompetent
      patients. A high index of suspicion is required for early diagnosis of this
      condition resulting in a good visual outcome with adequate treatment. mfERG and
      optical coherence tomography are useful in the diagnosis and follow-up of these
      patients.

PMID- 17024226
TI  - OPA1 alternate splicing uncouples an evolutionary conserved function in
      mitochondrial fusion from a vertebrate restricted function in apoptosis.
AB  - In most eucaryote cells, release of apoptotic proteins from mitochondria involves
      fission of the mitochondrial network and drastic remodelling of the cristae
      structures. The intramitochondrial dynamin OPA1, as a potential central actor of
      these processes, exists as eight isoforms resulting from the alternate splicing
      combinations of exons (Ex) 4, 4b and 5b, which functions remain undetermined.
      Here, we show that Ex4 that is conserved throughout evolution confers functions
      to OPA1 involved in the maintenance of the DeltaPsi(m) and in the fusion of the
      mitochondrial network. Conversely, Ex4b and Ex5b, which are vertebrate specific,
      define a function involved in cytochrome c release, an apoptotic process also
      restricted to vertebrates. The drastic changes of OPA1 variant abundance in
      different organs suggest that nuclear splicing can control mitochondrial dynamic
      fate and susceptibility to apoptosis and pathologies.

PMID- 17024227
TI  - Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3
      independent survival during monocytic differentiation.
AB  - We studied monocytic differentiation of primary mouse progenitor cells to
      understand molecular mechanisms of differentiation. We found a tightly controlled
      non-apoptotic activation of caspase-3 that correlated with differentiation.
      Although caspase activity was already detected during monocytic differentiation,
      a caspase-3 target has not been identified yet. We show that hematopoietic
      progenitor kinase 1 (HPK1) is processed towards its N- and C-terminal fragments
      during monocytic differentiation. While HPK1 is an immunoreceptor-proximal kinase
      in T and B cells, its role in myeloid cells is elusive. Here, we show that the N
      terminal cleavage product, HPK1-N, comprising the kinase domain, confers
      progenitor cell survival independent of the growth factor IL-3. Furthermore, HPK1
      N causes differentiation of progenitor cells towards the monocytic lineage. In
      contrast to full-length kinase, HPK1-N is constitutively active causing sustained
      JNK activation, Bad phosphorylation and survival. Blocking of caspase activity
      during differentiation of primary mouse progenitor cells leads to reduced HPK1-N
      levels, suppressed JNK activity and attenuated monocytic differentiation. Our
      work explains growth factor-independent survival during monocytic differentiation
      by caspase-mediated processing of HPK1 towards HPK1-N.

PMID- 17024228
TI  - Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage
      checkpoints, cell cycle arrest, and mitotic catastrophe.
AB  - Epidemiological studies revealed that amount of consumption of soy was inversely
      related to incidence of breast cancer. Genistein, the predominant isoflavone in
      soy, has been reported to reduce the incidence of breast cancer in animal models.
      To investigate whether genistein has a therapeutic effect on BRCA1-associated
      breast cancer, we treated Brca1 mutant mammary tumor cells with genistein. We
      showed that genistein treatment depleted the G1 population of cells, which was
      accompanied by an accumulation of cells at G2. Some genistein-treated cells
      entered mitosis; however, they exhibited chromosome abnormalities and maintained
      tetraploidy owing to abortive mitotic exit. A fraction of G2 cells underwent
      endoreduplication and became polyploid, which was accompanied by increased cell
      death through activating DNA damage response. Furthermore, our data indicated
      that Brca1 mutant cells were more sensitive to genistein than some other types of
      cancer cells, highlighting a good therapeutic potential of genistein for BRCA1
      associated breast cancer.

PMID- 17024229
TI  - The love-hate relationship between bacterial polysaccharides and the host immune
      system.
AB  - This article explores the fascinating relationship between the mammalian immune
      system and the bacteria that are present in the mammalian gut. Every human is an
      ecosystem that hosts 10(13)-10(14) bacteria. We review the evidence that
      immunomodulatory molecules produced by commensal bacteria in the gut have a
      beneficial influence on the development of certain immune responses, through
      eliciting the clonal expansion of CD4(+) T-cell populations. This process seems
      to contribute to the overall health of the host by offering protection against
      various diseases and might provide supporting evidence at a molecular level for
      the 'hygiene hypothesis' of allergic immune disorders.

PMID- 17024230
TI  - Enriching suicide gene bearing tumor cells for an increased bystander effect.
AB  - The success of cancer gene therapies requiring in vivo gene transfer is severely
      hampered by the low efficacy of gene transfer, which has been difficult to
      improve. We therefore established a novel strategy to increase the share of
      transduced cells post gene transfer. We hypothesized that in vivo selection of
      tumor cells transduced with a suicide gene effectively enriches these cells
      within a tumor, thus allowing for an increased bystander effect after the prodrug
      is given, leading to enhanced eradication of tumor cells. We reasoned that in
      vivo enrichment should be achieved by exploiting the metabolism of the suicide
      gene product. For this 'enrichment-eradication' strategy we chose a fusion gene
      of cytosine deaminase and uracil phosphoribosyl transferase. Positive selection
      (enrichment) was to be achieved by concurrently giving N-(phosphonacetyl)-L
      aspartate, an inhibitor of pyrimidine de novo synthesis, which leads to
      pyrimidine depletion-mediated death of non-transduced cells, and cytosine, to
      rescue fusion gene expressing cells via the pyrimidine salvage pathway. Negative
      selection (eradication) was to be induced by giving the prodrug 5-fluorocytosine.
      Indeed, murine NXS2 neuroblastoma cells transduced with the fusion gene were
      effectively enriched in vitro, leading to a near-complete bystander effect. In
      vivo enrichment-eradication of NXS2 cells led to decreased tumor growth. This
      proof-of-principle study shows that enrichment-eradication may compensate the
      effects of low in vivo gene transfer efficacy, a major obstacle in cancer gene
      therapy.

PMID- 17024231
TI  - Conversion of a tumor-binding peptide identified by phage display to a functional
      chimeric T cell antigen receptor.
AB  - Adoptive transfer of ex vivo expanded tumor-specific T cells is a promising
      therapeutic modality for promoting or augmenting antitumor immunity. Several
      groups, including ours, are developing antigen receptor gene transfer strategies
      as a means of generating effector cells for adoptive therapy. Chimeric antigen
      receptors (CARs) have been described that use single-chain antibodies or cytokine
      ligands as tumor targeting domains. Here, we describe the capacity of a tumor
      binding peptide identified by phage display combinatorial library screening to
      serve as a CAR targeting domain. A phage library-selected high-affinity 12-mer
      peptide (Bpep) specific for alpha(v) beta(6) integrin (alpha v beta6) was chosen
      for these studies. Primary human T cells were genetically modified to express the
      Bpep-CAR consisting of an alpha v beta6-specific peptide and human IgG4 hinge-Fc
      extracellular domain fused to the cytoplasmic tail of CD3-zeta. T cell expression
      of the Bpep-CAR was assessed by Western blot analysis, and trafficking of the
      Bpep-CAR to the cell surface was demonstrated by flow cytometry. Functionally,
      Bpep-CAR redirected cytotoxic T lymphocytes specifically kill integrin alpha v
      beta6+ ovarian tumor targets, and are activated for interferon gamma secretion.
      Our data suggest that large new repertoires of tumor-specific T cell antigen
      receptor transgenes might be available through merging combinatorial peptide
      libraries with CAR construct design.

PMID- 17024233
TI  - Enhancement of adenoviral MDA-7-mediated cell killing in human lung cancer cells
      by geldanamycin and its 17-allyl- amino-17-demethoxy analogue.
AB  - Our previous studies demonstrated that adenovirus-mediated overexpression of
      melanoma differentiation-associated gene-7 (Ad-mda7) leads to rapid induction of
      double-stranded RNA-dependent protein kinase (PKR) and activation of its
      downstream targets, resulting in apoptosis induction in human lung cancer cells.
      Here, we report that Ad-mda7 and the benzoquinone ansamycin geldanamycin (GA)
      interact in a highly synergistic manner to induce cell death in human lung cancer
      cells. Co-administration of Ad-mda7 and GA did not modify expression of MDA-7,
      and was not associated with further PKR induction and activation; instead the
      enhanced cytotoxicity of this combination was associated with inactivation of AKT
      by GA. By surface staining using anti-E-cadherin monoclonal antibody and flow
      cytometry, we found that treatment with the combination of Ad-mda7 and GA
      increased E-cadherin levels in these cancer cells. Ad-mda7 and GA cotreatment
      also inhibited lung cancer cell motility by increasing the beta-catenin/E
      cadherin association. Moreover, combination of GA derivative 17-allyl-amino, 17
      demethoxygeldanamycin (17AAG), with Ad-mda7 resulted in enhancement of cell death
      in A549 and H460 human lung cancer cells.

PMID- 17024232
TI  - Vascular endothelial growth factor promoter-based conditionally replicative
      adenoviruses for pan-carcinoma application.
AB  - Treatment of advanced lung cancer is one of the major challenges in current
      medicine because of the high morbidity and mortality of the disease. Advanced
      stage lung cancer is refractory to conventional therapies and has an extremely
      poor prognosis. Thus, new therapeutic approaches are needed. Lung tumor formation
      depends on angiogenesis in which the vascular endothelial growth factor (VEGF)
      produced by cancer cells plays a pivotal role. Neutralizing VEGF with a soluble
      VEGF receptor suppresses tumor growth; however, the anticancer effect with this
      therapy is weakened after the intratumoral vascular network is completed. In this
      study, we turned the expression of VEGF by tumors to therapeutic advantage using
      a conditionally replication-competent adenovirus (CRAd) in which the expression
      of E1 is controlled by the human VEGF promoter. This virus achieved good levels
      of viral replication in lung cancer cells and induced a substantial anticancer
      effect in vitro and in vivo. As a further enhancement, the cancer cell killing
      effect was improved with tropism modification of the virus to express the knob
      domain of Ad3, which improved infectivity for cancer cells. These VEGF promoter
      based CRAds also showed a significant cell killing effect for various types of
      cancer lines other than lung cancer. Conversely, the VEGF promoter has low
      activity in normal tissues, and the CRAd caused no damage to normal bronchial
      epithelial cells. Since tumor-associated angiogenesis via VEGF signalling is
      common in many types of cancers, these CRAds may be applicable to a wide range of
      tumors. We concluded that VEGF promoter-based CRAds have the potential to be an
      effective strategy for cancer treatment.

PMID- 17024244
TI  - Joint inspection of services for people with learning disabilities in Scotland:
      compliance or commitment?
AB  - PURPOSE: The article describes the development of a practical model of joint,
      integrated inspection of managed care services for people with learning
      disabilities in Scotland. The model will give a reliable measure of the impact
      services are making to people's lives and the quality of service that individuals
      are actually receiving. CONTEXT OF CASE: At present health, social services and
      education services for people with learning disabilities in Scotland are
      inspected separately, by up to nine different agencies. The first joint,
      integrated inspections of all services for people with learning disabilities in
      Scotland will take place in 2006. This is the first inspection of its kind in the
      UK, and the first to involve carers and people with learning disabilities on the
      inspection team. DATA SOURCES: Quality Outcome Indicators were developed in 21
      different areas, or domains. Evidence based best practice, and evaluative data
      from previous inspections were the primary sources of data. CASE DESCRIPTION:
      This paper reviews the background and rationale for the integrated, joint
      inspection process. Strengths and constraints of this approach to inspection are
      discussed, including the crucial importance of commitment from services and from
      inspectors, rather than mere compliance with demands. Some guidance on how to
      fully involve staff, carers and services users in the inspection process is
      given. CONCLUSIONS AND DISCUSSION: The model will produce data to inform decision
      making for managers in integrated services and give services users clear
      information about how well local needs are being met, what areas need
      development, and what capacity the organisations have to improve. The model of
      inspection may be of interest to practitioners in a national and international
      context. The model will be evaluated, following the first joint inspection.

PMID- 17024245
TI  - Absence of bacterially induced RELMbeta reduces injury in the dextran sodium
      sulfate model of colitis.
AB  - Although inflammatory bowel disease (IBD) is the result of a dysregulated immune
      response to commensal gut bacteria in genetically predisposed individuals, the
      mechanism(s) by which bacteria lead to the development of IBD are unknown.
      Interestingly, deletion of intestinal goblet cells protects against intestinal
      injury, suggesting that this epithelial cell lineage may produce molecules that
      exacerbate IBD. We previously reported that resistin-like molecule beta
      (RELMbeta; also known as FIZZ2) is an intestinal goblet cell-specific protein
      that is induced upon bacterial colonization whereupon it is expressed in the
      ileum and colon, regions of the gut most often involved in IBD. Herein, we show
      that disruption of this gene reduces the severity of colitis in the dextran
      sodium sulfate (DSS) model of murine colonic injury. Although RELMbeta does not
      alter colonic epithelial proliferation or barrier function, we show that
      recombinant protein activates macrophages to produce TNF-alpha both in vitro and
      in vivo. RELMbeta expression is also strongly induced in the terminal ileum of
      the SAMP1/Fc model of IBD. These results suggest a model whereby the loss of
      epithelial barrier function by DSS results in the activation of the innate
      mucosal response by RELMbeta located in the lumen, supporting the hypothesis that
      this protein is a link among goblet cells, commensal bacteria, and the
      pathogenesis of IBD.

PMID- 17024246
TI  - Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel
      immune escape mechanism.
AB  - The adenoviral protein E3-14.7K (14.7K) is an inhibitor of TNF-induced apoptosis,
      but the molecular mechanism underlying this protective effect has not yet been
      explained exhaustively. TNF-mediated apoptosis is initiated by ligand-induced
      recruitment of TNF receptor-associated death domain (TRADD), Fas-associated death
      domain (FADD), and caspase-8 to the death domain of TNF receptor 1 (TNFR1),
      thereby establishing the death-inducing signaling complex (DISC). Here we report
      that adenovirus 14.7K protein inhibits ligand-induced TNFR1 internalization.
      Analysis of purified magnetically labeled TNFR1 complexes from murine and human
      cells stably transduced with 14.7K revealed that prevention of TNFR1
      internalization resulted in inhibition of DISC formation. In contrast, 14.7K did
      not affect TNF-induced NF-kappaB activation via recruitment of receptor
      interacting protein 1 (RIP-1) and TNF receptor-associated factor 2 (TRAF-2).
      Inhibition of endocytosis by 14.7K was effected by failure of coordinated
      temporal and spatial assembly of essential components of the endocytic machinery
      such as Rab5 and dynamin 2 at the site of the activated TNFR1. Furthermore, we
      found that the same TNF defense mechanisms were instrumental in protecting wild
      type adenovirus-infected human cells expressing 14.7K. This study describes a new
      molecular mechanism implemented by a virus to escape immunosurveillance by
      selectively targeting TNFR1 endocytosis to prevent TNF-induced DISC formation.

PMID- 17024247
TI  - Role of different pathways of the complement cascade in experimental bullous
      pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease
      associated with autoantibodies directed against the hemidesmosomal proteins BP180
      and BP230 and inflammation. Passive transfer of antibodies to the murine BP180
      (mBP180) induces a skin disease that closely resembles human BP. In the present
      study, we defined the roles of the different complement activation pathways in
      this model system. Mice deficient in the alternative pathway component factor B
      (Fb) and injected with pathogenic anti-mBP180 IgG developed delayed and less
      intense subepidermal blisters. Mice deficient in the classical pathway component
      complement component 4 (C4) and WT mice pretreated with neutralizing antibody
      against the first component of the classical pathway, C1q, were resistant to
      experimental BP. These mice exhibited a significantly reduced level of mast cell
      degranulation and polymorphonuclear neutrophil (PMN) infiltration in the skin.
      Intradermal administration of compound 48/80, a mast cell degranulating agent,
      restored BP disease in C4(-/-) mice. Furthermore, C4(-/-) mice became susceptible
      to experimental BP after local injection of PMN chemoattractant IL-8 or local
      reconstitution with PMNs. These findings provide the first direct evidence to our
      knowledge that complement activation via the classical and alternative pathways
      is crucial in subepidermal blister formation in experimental BP.

PMID- 17024248
TI  - Rai1 duplication causes physical and behavioral phenotypes in a mouse model of
      dup(17)(p11.2p11.2).
AB  - Genomic disorders are conditions that result from DNA rearrangements, such as
      deletions or duplications. The identification of the dosage-sensitive gene(s)
      within the rearranged genomic interval is important for the elucidation of genes
      responsible for complex neurobehavioral phenotypes. Smith-Magenis syndrome is
      associated with a 3.7-Mb deletion in 17p11.2, and its clinical presentation is
      caused by retinoic acid inducible 1 (RAI1) haploinsufficiency. The reciprocal
      microduplication syndrome, dup(17)(p11.2p11.2), manifests several neurobehavioral
      abnormalities, but the responsible dosage-sensitive gene(s) remain undefined. We
      previously generated a mouse model for dup(17)(p11.2p11.2), Dp(11)17/+, that
      recapitulated most of the phenotypes observed in human patients. We have now
      analyzed compound heterozygous mice carrying a duplication [Dp(11)17] in one
      chromosome 11 along with a null allele of Rai1 in the other chromosome 11
      homologue [Dp(11)17/Rai1(-) mice] in order to study the relationship between Rai1
      gene copy number and the Dp(11)17/+ phenotypes. Normal disomic Rai1 gene dosage
      was sufficient to rescue the complex physical and behavioral phenotypes observed
      in Dp(11)17/+ mice, despite altered trisomic copy number of the other 18 genes
      present in the rearranged genomic interval. These data provide a model for
      variation in copy number of single genes that could influence common traits such
      as obesity and behavior.

PMID- 17024249
TI  - Taming the free radical shrew - learning to control homolytic reactions at higher
      heteroatoms.
AB  - Free radical chemistry has come a long way in a relatively short period of time.
      Armed with mechanistic and rate constant data, the synthetic practitioner can now
      apply free radical chemistry to the synthesis of many different classes of target
      molecule with confidence. This Feature Article highlights progress made in the
      understanding and application of free radical reactions at main group higher
      heteroatoms and demonstrates how this knowledge can be used to construct
      interesting higher heterocycles, many of which exhibit biological activity,
      through the use of intramolecular homolytic substitution chemistry.

PMID- 17024250
TI  - Enantioselective nitroaldol (Henry) reaction using copper(II) complexes of (-)
      sparteine.
AB  - The dichloro[(-)-sparteine-N,N']copper(II) complex provides Henry adducts with
      high enantioselectivities (73-97% ee) in Henry reaction between nitromethane and
      various aldehydes.

PMID- 17024252
TI  - Reciprocal template effects in a simple synthetic system.
AB  - Two mutually-complementary templates are capable of catalysing the formation of
      each other, creating a framework for their reciprocal replication.

PMID- 17024251
TI  - Porous 3-D honeycomb architecture by self-assembly of helical H-bonded molecular
      tapes.
AB  - Enantiopure dipeptide-derived 1,3,5-triazepan-2,6-diones and form H-bonded 3(1)
      helical molecular tapes with P chirality in the solid state; in the case of ,
      these columnar tapes self-assemble through aromatic-aromatic interactions to give
      hollow tubular structures.

PMID- 17024253
TI  - Gyroscope-like molecules consisting of three-spoke stators that enclose
      "switchable" neutral dipolar rhodium rotators; reversible cycling between faster
      and slower rotating Rh(CO)I and Rh(CO)2I species.
AB  - trans-Rh(CO)(Cl)(P((CH(2))(14))(3)P) is prepared from trans
      Rh(CO)(Cl)(P((CH(2))(6)CH[double bond, length as m-dash]CH(2))(3))(2) by a
      metathesis/hydrogenation sequence, and converted by substitution or addition
      reactions to Rh(CO)(I), Rh(CO)(2)(I), Rh(CO)(NCS), and Rh(CO)(Cl)(Br)(CCl(3))
      species; the Rh(CO)(Cl) and Rh(CO)(I) moieties rapidly rotate within the cage
      like diphosphine, but the other rhodium moieties do not.

PMID- 17024254
TI  - Combined optimization using Cultural and Differential Evolution: application to
      crystal structure solution from powder diffraction data.
AB  - The principles of social and biological evolution have been combined in a
      Cultural Differential Evolution hybrid global optimization technique and applied
      to crystal structure solution.

PMID- 17024255
TI  - High pressure co-ordination chemistry of a palladium thioether complex: pressure
      versus electrons.
AB  - The mononuclear Pd(ii) complex cis-[PdCl(2)([9]aneS(3))]([9]aneS(3)= 1,4,7
      trithiacyclononane) converts at 44 kbar pressure into an intensely coloured chain
      polymer, which exhibits distorted octahedral co-ordination at the metal centre
      and an unprecedented [1233] conformation for the thioether crown.

PMID- 17024256
TI  - A ratiometric and non-enzymatic luminescence assay for uric acid: differential
      quenching of lanthanide excited states by anti-oxidants.
AB  - The excited states of Tb and Eu complexes of a common macrocyclic ligand are
      quenched preferentially by electron transfer from the urate anion, allowing the
      creation of a new assay to measure uric acid in biological fluids.

PMID- 17024257
TI  - ATP recognition and sensing with a phenanthroline-containing polyammonium
      receptor.
AB  - A new polyammonium receptor is able to selectively recognise and sense ATP among
      triphosphate nucleotides, thanks to ATP-induced quantitative quenching of its
      fluorescence emission.

PMID- 17024258
TI  - Electrochemical preparation of platinum nanothorn assemblies with high surface
      enhanced Raman scattering activity.
AB  - Platinum nanothorn assemblies with sharp tips and edges were prepared, which
      exhibit high surface enhanced Raman scattering (SERS) activity and yield an
      enhancement factor as high as 2000 for adsorbed pyridine.

PMID- 17024259
TI  - Enantioselective rhodium-catalyzed addition of arylboronic acids to
      trifluoromethyl ketones.
AB  - The catalytic asymmetric 1,2-addition of a series of arylboronic acids to 2,2,2
      trifluoroacetophenones is described with high isolated yields (up to 96%) and
      good enantioselectivities (up to 83% ee) using a rhodium(I)/phosphoramidite
      catalyst.

PMID- 17024260
TI  - Coupling-isomerization-Claisen sequences - mechanistic dichotomies in hetero
      domino reactions.
AB  - A new coupling-isomerization-Claisen domino reaction starting from electron
      deficient halides and 1-(hetero)aryl propargyl trityl ethers dichotomizes in the
      concluding steps of the sequence and gives rise to the formation of
      tricyclo[3.2.1.0(2,7)]oct-3-enes, enones, 1H-isochromenes, or indans as a
      consequence of minute differences of substituent effects.

PMID- 17024261
TI  - Three-dimensionally ordered macroporous carbons having walls composed of hollow
      mesosized spheres.
AB  - Three-dimensionally ordered macroporous carbons were prepared from bimodal
      polymer-silica colloidal crystals; the resulting carbons had interconnected
      macropores, and the walls of the macropores were composed of hollow mesosized
      spheres.

PMID- 17024262
TI  - Thermoreversible sol-gel transition of an aqueous solution of polyrotaxane
      composed of highly methylated alpha-cyclodextrin and polyethylene glycol.
AB  - Novel thermo-gelling aqueous solution systems are developed with a polyrotaxane,
      consisting of methylated alpha-cyclodextrin and polyethylene glycol, based on the
      slide-ring properties of the macrocycles along the linear chain.

PMID- 17024263
TI  - Silver-catalyzed hydrosilylation of aldehydes.
AB  - Silver triflate, either alone or in the presence of an appropriate phosphine or
      NHC ligand, has been shown to catalyze the chemoselective hydrosilylation of
      aromatic and aliphatic aldehydes to yield silyl ethers, thus representing the
      first systematic application of silver species as catalysts for the
      hydrosilylation of unsaturated organic substrates.

PMID- 17024264
TI  - Interfacial layer interactions: their effects on synclinic and anticlinic smectic
      mesophase behaviour in liquid crystals.
AB  - Through the use of bulky cyclic terminal groups, anticlinic smectic C phases have
      been observed in 2-methylbutyl materials based on the MHPOBC motif.

PMID- 17024265
TI  - Mechanism for the elimination of aromatic molecules from polyenes in tandem mass
      spectrometry.
AB  - We report here a general mechanism for the elimination of aromatic molecules from
      polyene containing natural products of several compound classes in tandem mass
      spectrometry.

PMID- 17024266
TI  - Synthesis of propargylic fluorides from allenylsilanes.
AB  - Allenylsilanes reacted at room temperature in acetonitrile with Selectfluor, an
      electrophilic fluorinating reagent, to give secondary propargylic fluorides in
      moderate to good yields; mechanistically, a side-product resulting from a 1,2
      silyl shift testifies to the presence of a cationic intermediate.

PMID- 17024267
TI  - Synthesis of luminescent heterometallic bis-lanthanide complexes via selective,
      sequential metallation.
AB  - A modular synthetic method for the differential incorporation of two lanthanide
      ions into a single molecular scaffold is reported; the mixed bimetallic Tb/Eu
      complex displays an interesting solvent polarity-dependent ratiometric
      luminescence.

PMID- 17024268
TI  - The tuneable complexation of gold nanoparticles.
AB  - Mixed monolayer protected gold nanoparticles have been fabricated incorporating
      1,5-dialkyloxynaphthalene moieties that are capable of forming complexes with the
      tetracationic cyclophane cyclobis(paraquat-p-phenylene); electrochemical
      reduction of the cyclophane or the addition of tetrathiafulvalene results in
      disassembly of the complexes.

PMID- 17024269
TI  - Galactose Oxidase models: 19F NMR as a powerful tool to study the solution
      chemistry of tripodal ligands in the presence of copper(II).
AB  - In copper(ii) complexes of tripodal ligands, the protonation state of the phenol
      moiety, and its position (axial vs. equatorial), are easily assessed by (19)F
      NMR.

PMID- 17024270
TI  - Efficient stabilization of copper(III) in tetraaza pseudo-macrocyclic oxime-and
      hydrazide ligands with adjustable cavity size.
AB  - Substitution of the amide donors in open-chain {2N(oxime), 2N(amide)} ligands by
      hydrazide donors gives new pseudo-macrocyclic copper complexes that show a
      significant decrease of the Cu(3+/2+) redox potentials in both mono- and
      polynuclear systems, thus demonstrating a pronounced capacity of such ligand
      systems to efficiently stabilize the trivalent copper.

PMID- 17024271
TI  - Unprecedented intermolecular C-H bond activation of a solvent toluene molecule
      leading to a seven-membered platinacycle.
AB  - A novel platinum-mediated process involving intermolecular activation of a
      C(aryl)-H bond of toluene, intramolecular activation of an imine C(aryl)-Cl bond
      and formation of a C-C bond is reported.

PMID- 17024272
TI  - Shape-persistent macrocycle with a self-complementary recognition pattern based
      on diacetylene-linked alternating hexylbenzene and perfluorobenzene rings.
AB  - The synthesis and characterization of a shape-persistent macrocycle, consisting
      of alternating electron rich and electron poor sub-units as a self-complementary
      recognition pattern, is reported, and its increased tendency to form dimer
      complexes in solution is demonstrated and discussed.

PMID- 17024273
TI  - Direct synthesis of 1,1-diarylalkenes from alkenyl phosphates via nickel(0)
      catalysed Suzuki-Miyaura coupling.
AB  - A combination of Ni(COD)(2) and PCy(3) promotes effectively the Suzuki-Miyaura
      cross coupling of 1-arylalkenyl phosphates with aryl boronic acids with yields
      attaining 99%.

PMID- 17024274
TI  - [Zn(n)(polyox)(pmtz)n]: the first polyoxalate-containing coordination polymer
      from an unforeseen chemical rearrangement of 5-pyrimidyl-tetrazole under
      hydrothermal conditions.
AB  - The compound [Zn(2)(polyox)(pmtz)(2)], which has been prepared by the
      hydrothermal reaction of ZnCl(2) and Napmtz (5-pyrimidyl-tetrazolate), exhibits a
      unique 2D network with (6,3) topology, in which Zn(II) ions are connected by pmtz
      and polyoxalate-bridging ligands (generated in situ from the breaking of the
      pmzt(-) ligand). This is the first structural report on a polyoxalate species.

PMID- 17024275
TI  - Gold(I)-catalyzed intramolecular hydroamination of unactivated alkenes with
      carboxamides.
AB  - N-Alkenyl carboxamides undergo gold-catalyzed intramolecular exo-hydroamination
      to form nitrogen heterocycles in excellent yield.

PMID- 17024276
TI  - Amplification of chirality in liquid crystals.
AB  - The amplification of molecular chirality by liquid crystalline systems is widely
      applied in investigations towards enantioselective solvent-solute interactions,
      chiral supramolecular assemblies, smart materials, and the development of liquid
      crystal displays. Here we present an overview of recent achievements in the
      development of new chiral dopant systems for the generation of cholesteric liquid
      crystalline phases. Based on a distinction between shape-persistent and bistable
      dopants, several dopant classes will be discussed.

PMID- 17024277
TI  - Planar bilayer studies reveal multiple conductance states for synthetic anion
      transporters.
AB  - Compounds of the general type R(1)(2)NCOCH(2)OCH(2)CO-(Gly)(3)-Pro-(Gly)(3)
      OCH(2)Ph insert in phospholipid bilayers and conduct ions. Different levels of
      activity were observed when R(1) was either decyl or octadecyl, as judged either
      by Cl(-) release, detected by ion selective electrodes, or carboxyfluorescein
      dequenching, detected by fluorescence. Either method reports average behavior for
      all ionophores over all liposomes. These methods also show that at least two
      ionophores are involved in the formation of each pore. Planar bilayer experiments
      reported here confirm pore formation by these compounds but identify more than
      one conductance state for each. The pseudo-dimer, in which two molecules of the
      type shown above are covalently linked, shows only two conductance states, of
      which one is dominant. This state has been characterized by use of a current
      voltage plot.

PMID- 17024278
TI  - The first total synthesis of xenitorins B and C: assignment of absolute
      configuration.
AB  - Starting from (-)-beta-pinene, the first total synthesis of xenitorins B and C
      has been accomplished, which also allowed the assignment of their absolute
      configuration.

PMID- 17024279
TI  - Sulfanyl radical promoted C4'-C5' bond scission of 5'-oxo-3',4'-didehydro-2',3'
      dideoxynucleosides.
AB  - Treatment of C5'-aldehydes, under mildly basic conditions leads to the formation
      of 3',4'-didehydroaldehydes, and furfural. Sulfanyl radical addition eventually
      gives rise to the lactones, through C4'-C5' bond scission of the 1,2-dioxetane
      intermediates.

PMID- 17024280
TI  - Novel, efficient total synthesis of natural 20(S)-camptothecin.
AB  - Enantiopure 20(S)-camptothecin has been prepared from a known hydroxypyridone
      through a novel approach that involves a Claisen rearrangement, an asymmetric
      nucleophilic ethylation, a Heck coupling and a Friedlander condensation as the
      key transformations.

PMID- 17024281
TI  - Direct synthesis of tricyclic 5H-pyrido[3,2,1-ij]quinolin-3-one by domino
      palladium catalyzed reaction.
AB  - Unexpectedly, the palladium catalyzed coupling reaction of acrolein with 8
      bromoquinoline gave 5H-pyrido[3,2,1-ij]quinolin-3-one in a single step.

PMID- 17024282
TI  - Polycationic calix[8]arenes able to recognize and neutralize heparin.
AB  - A mutual induced fit mechanism is responsible for the exceptional complexation
      performances exhibited by calix[8]arene polycations towards heparin. The
      recognition process was studied in comparison with two other heparin antagonists:
      protamine and polylysine. The arrangement of multiple functional groups on the
      flexible macrocyclic scaffold of calix[8]arene, with respect to the
      conformationally rigid protamine and low ordered polylysine, allowed a mutual
      adaptability between calixarene polycations and heparin, significantly enhancing
      the recognition performances. Fluorescence, NMR titration, and activated partial
      thromboplastin time (aPTT) experiments confirmed that these calixarene
      derivatives have a very high specificity and affinity towards heparin
      neutralization as in aqueous solution as in blood. Analogous results were
      obtained with low molecular weight heparin (LMWH) whose effect protamine is
      unable to completely reverse.

PMID- 17024283
TI  - Synthesis and biological evaluation of two chemically modified peptide epitopes
      for the class I MHC protein HLA-B*2705.
AB  - The T-cell receptor of a CD8(+) T-cell recognises peptide epitopes bound by class
      I major histocompatibility complex (MHC) glycoproteins presented in a groove on
      their upper surface. Within the groove of the MHC molecule are 6 pockets, two of
      which mostly display a high degree of specificity for binding amino acids capable
      of making conserved and energetically favourable contacts with the MHC. One type
      of MHC molecule, HLA-B*2705, preferentially binds peptides containing an arginine
      at position 2. In an effort to increase the affinity of peptides for HLA-B*2705,
      potentially leading to better immune responses to such a peptide, we synthesised
      two modified epitopes where the amino acid at position 2 involved in anchoring
      the peptide to the class I molecule was replaced with the alpha-methylated
      beta,gamma-unsaturated arginine analogue 2-(S)-amino-5-guanidino-2-methyl-pent-3
      enoic acid. The latter was prepared via a multi-step synthetic sequence, starting
      from alpha-methyl serine, and incorporated into dipeptides which were fragment
      coupled to resin-bound heptameric peptides yielding the target nonameric
      sequences. Biological characterisation indicated that the modified peptides were
      poorer than the native peptides at stabilising empty class I MHC complexes, and
      cells sensitised with these peptides were not recognised as well by cognate
      CD8(+) T-cells, where available, compared to those sensitised with the native
      peptide. We suggest that the modifications made to the peptide have decreased its
      ability to bind to the peptide binding groove of HLA-B*2705 molecules which may
      explain the decrease in recognition by cytotoxic T-cells when compared to the
      native peptide.

PMID- 17024284
TI  - Conformational analogues of Oxamflatin as histone deacetylase inhibitors.
AB  - Conformational analogues of the hydroxamic acid Oxamflatin compounds, have been
      synthesised to enable evaluation of the impact of varying the linking section on
      histone deacetylase inhibition. Preliminary testing indicates treatment of
      leukaemia cells with each of the analogues leads to significant inhibition of
      histone deacetylase and reduction in cell growth and proliferation.

PMID- 17024285
TI  - Oxidative reactions of 6-pentyl indolo[3,2-b]carbazole: formation of novel C-C
      and C-N coupled dimers.
AB  - The oxidative coupling reactions of 6-pentyl-5,11-dihydroindolo[3,2-b]carbazole
      have been studied and as a result, a number of novel dimers of the indolo[3,2
      b]carbazole derivative have been prepared, forming C-C coupled compound when
      treated with FeCl(3) x 6H(2)O or C-N coupled compounds and when oxidized with air
      or Pd(OAc)(2), respectively.

PMID- 17024286
TI  - gamma-Glutamyl transpeptidase acylation with peptidic substrates: free energy
      relationships measured by an HPLC kinetic assay.
AB  - gamma-Glutamyl transpeptidase (GGT, EC 2.3.2.2) is a highly glycosylated
      heterodimeric enzyme linked to the external cellular membrane that catalyzes the
      hydrolysis of glutathione as well as the transfer of its gamma-glutamyl group to
      amino acids and dipeptides in a transpeptidation reaction. The measurement of
      both the hydrolytic and transpeptidation activity of this important enzyme is a
      challenge, since its native substrates are not highly chromogenic. We have
      developed an HPLC-based method for the quantitative photometric detection of
      numerous enzyme substrates and products, after their pre-column derivation with
      dabsyl chloride. The broad applicability of this method was demonstrated in the
      kinetic investigation of transpeptidation reactions of rat kidney GGT with
      glutathione, its native substrate, as well as a series of pertinent glutathione
      analogues. The pH-rate profile constructed for glutathione confirmed the
      dependence on the ionisation state of at least two residues. Analysis of the free
      energy relationships in the series of synthetic peptidic substrate analogues
      revealed the importance of enzyme-substrate interactions unrelated to amine
      leaving group basicity during the acylation step. These results are further
      interpreted in the context of the recently published structure for a similar GGT.

PMID- 17024287
TI  - Solution structures by NMR of a novel antifungal drug: Petriellin A.
AB  - Petriellin A is a novel cyclic depsipeptide antifungal compound consisting of
      nine l-configured residues, one d-phenyllactic acid (PhLac) and three unknown
      chiral centres: two N-methyl-threonines (MeThr1 & MeThr2) and one N-methyl
      isoleucine (MeIle). NMR experiments including 2D ROESY, NOESY along with
      structural and energy calculations predicted that the unknown chiral centres were
      all l-configured, which was later verified chemically. Simulated annealing,
      dynamics calculations and minimisation processes showed Petriellin A to have a
      folded "C-shaped" structure.

PMID- 17024288
TI  - Stereocontrolled synthesis of highly functionalized spirocyclic pyrans.
AB  - Highly functionalized spirocyclic pyrans can be obtained through the Achmatowicz
      rearrangement of furyl carbinols by taking advantage of the different rates of
      reaction for epoxidation and nucleophilic addition. Through this methodology,
      spirocyclic units of various ring sizes can be selectively generated with
      complete stereocontrol.

PMID- 17024289
TI  - Boronated protohaemins: synthesis and in vivo antitumour efficacy.
AB  - The conjugates of porphyrin macrocycles with boron-containing polyhedra are under
      investigation as agents for binary treatment strategies of cancer. Aiming at the
      design of photoactive compounds with low-to-zero dark toxicity, we synthesized a
      series of carboranyl and monocarbon-carboranyl derivatives of protohaemin IX
      using the activation of porphyrin carboxylic groups with di-tert-butyl
      pyrocarbonate or pivaloyl chloride. The water-soluble 1,3,5,8-tetramethyl-2,4
      divinyl-6(7)-[2'-(closo-monocarbon-carborane-1''-yl)methoxycarbonylethyl]-7(6)
      (2'-carboxyethyl)porphyrin Fe(III) (compound 9) exerted no discernible
      cytotoxicity for cultured mammalian cells, nor did it cause general toxicity in
      rats. Importantly, 9 demonstrated dose-dependent activity as a phototoxin in
      photodynamic therapy of M-1 sarcoma-bearing rats. In animals injected with 20 mg
      kg(-1) of 9, the tumours shrank by day 3 after one single irradiation of the
      tumour with red laser light. Between 7 and 14 days post-irradiation, 88.9% of
      rats were tumour-free; no recurrence of the disease was detectable within at
      least 90 days. Protohaemin IX alone was without effect, indicating that
      boronation is important for the phototoxic activity of 9. This is the first study
      that presents the synthesis and preclinical in vivo efficacy of boronated
      derivatives of protohaemin as phototoxins. The applicability in photodynamic
      treatment broadens the therapeutic potential of boronated porphyrins beyond their
      conventional role as radiosensitizers in boron neutron capture therapy.

PMID- 17024290
TI  - Synthesis of 5-alkylidene-1,3-dioxane-4,6-diones, an easily accessible family of
      axially chiral alkenes: preparation in non-racemic form and platinum binding
      studies.
AB  - A general synthetic route to 5-alkylidene-1,3-dioxane-4,6-diones, which are a
      family of axially chiral alkenes, is described. Conformational issues are
      explored and the platinum-binding properties of these species are discussed. That
      these alkenes exist as stable enantiomers is established by their partial kinetic
      resolution upon reaction with cysteine.

PMID- 17024291
TI  - Guanine-thymine intrastrand cross-linked lesion containing oligonucleotides: from
      chemical synthesis to in vitro enzymatic replication.
AB  - An intrastrand cross-link lesion, in which two neighboring nucleobases are
      covalently tethered, has been site-specifically synthesized into defined sequence
      oligonucleotides in order to perform in vitro replication studies using either
      bacterial replicative or translesional synthesis polymerases. The investigated
      tandem base lesion that involves a cross-link between the methylene group of
      thymine and the C8 of an adjacent guanine residue has been prepared by UV
      photolysis under anaerobic condition of the photolabile precursor 5
      (phenylthiomethyl)-2'-deoxyuridine that has been site-specifically incorporated
      into a 9-mer oligonucleotide. After ligation, the lesion-containing modified
      oligonucleotide was used as a DNA template in primer extension reactions
      catalyzed by several DNA polymerases including the fragment Klenow exo-(Kf-) of
      E. coli polymerase I, the Thermus aquaticus polymerase (Taq pol) and the E. coli
      translesional DNA polymerase Pol IV (dinB). It was found that the primer
      extension reaction was stopped after the incorporation of the correct nucleotide
      dAMP opposite the 3'-thymine residue of guanine(C8-CH2) thymine lesion by Kf- and
      Pol IV; however it was noted that the efficiency of the nucleotide incorporation
      was reduced. In contrast, the Taq polymerase was totally blocked at the
      nucleotide preceding the tandem lesion. These results are strongly suggestive
      that the present intrastrand cross-link lesion, if not repaired, would constitute
      a blocking lesion for prokaryotic DNA polymerases, being likely lethal for the
      cell.

PMID- 17024292
TI  - cis-3,5-Cyclohexadiene-1,2-diol derivatives: facial selectivity in their Diels
      Alder reactions with ethylenic, acetylenic and azo dienophiles.
AB  - The Diels-Alder reactions of maleimide with the acetonide derivative (6a) of cis
      3,5-cyclohexadiene-1,2-diol (1a) in various solvents showed facial selectivities
      ranging from 1 : 1 to 1 : 9. The same derivative 6a reacted in benzene with
      ethylenic dienophiles with generally modest facial selectivity, but acetylenic
      dienophiles added exclusively anti to the oxygen functions of 6a. Dimerization of
      cyclic acetals 6a and 7 was mainly, but for 6a not exclusively, by anti addition
      with respect to both the diene and the dienophile partners. Reactions of azo
      dienophiles with derivatives of 1a were predominantly by anti addition, but the
      diol itself (1a) gave the syn adduct as the major product.

PMID- 17024293
TI  - Dermatological drug dosage in the elderly.
AB  - The elderly population is increasing and drug dosing requires special
      considerations for efficacy and decreasing toxicity. This overview provides
      algorithms for adjusting drug and dosage based on current evidence-based
      knowledge with emphasis on drugs prescribed in dermatological practice.

PMID- 17024294
TI  - Pigmentary disorders in Asian skin: treatment with laser and intense pulsed light
      sources.
AB  - The development of selective photothermolysis has enabled removal of targets such
      as melanin. Both lasers and intense pulsed light (IPL) sources have been used in
      the treatment of pigmented lesions, however careful selection is important to
      ensure success. This is especially true in darker skinned individuals where the
      risk of postinflammatory hyperpigmentation (PIH) is high. The advent of the Q
      switched laser, IPL, and now fractional photothermolysis (Fraxel, Reliant
      Technologies) offers a variety of ways to treat epidermal and dermal pigmentary
      disorders.

PMID- 17024295
TI  - Neonatal intestinal volvulus due to a persistent right vitelline artery.
AB  - We report a case of neonatal intestinal volvulus around a persistent right
      vitelline artery, presenting as an aberrant parieto-mesenteric band on
      exploratory laparotomy. To our knowledge, this is the first case report in the
      English literature of a persistent right vitelline artery causing axial
      intestinal volvulus in a neonate. A review of the literature and the
      embryopathogenesis is discussed, as well as the importance of emergent diagnoses
      of such lesions.

PMID- 17024296
TI  - A unique service in UK delivering Plastibell circumcision: review of 9-year
      results.
AB  - Muslim infants undergo circumcision for religious reasons and Bradford has a high
      Muslim population. The National Health Service in UK does not provide religious
      circumcision, so in 1996 a nurse-delivered circumcision service led by consultant
      urologists was set up at a no-profit and cost-only basis. Plastibell circumcision
      was offered to all infants between 6 and 14 weeks old and performed under local
      anaesthesia. Information leaflets and videotapes about the procedure were
      available to parents prior to the procedure. A three monthly audit of the service
      was undertaken. Between July 1996 and June 2005 (9 years) 1,129 circumcisions
      were performed. The common complications were problems with the ring (3.6%) and
      bleeding (3%). Overall, there was 96% satisfaction rate among the service users.
      The Plastibell technique for circumcision is a simple method and can be safely
      performed by trained nurses with acceptable complication rates.

PMID- 17024297
TI  - Non-neuronal acetylcholine and choline acetyltransferase in oviductal epithelial
      cells of cyclic and pregnant pigs.
AB  - Certain female reproductive tissues are known to express the non-neuronal
      cholinergic system. Using different experimental approaches, we tested the
      hypothesis that acetylcholine (ACh) in the porcine oviduct may also be derived
      from non-neuronal structures. Immunohistochemistry was performed to detect
      acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) in different
      segments of the oviduct of cyclic and pregnant sows. Immunohistochemical
      experiments revealed strong immunoexpression of ChAT in the entire oviductal
      epithelium at metoestrus. Thereby, a particular pronounced staining was found in
      the supranuclear region of almost all epithelial cells. Immunostaining of ChAT
      decreased markedly during dioestrus and prooestrus stages, respectively. At
      prooestrus, ChAT immunoreactivity was confined to ciliated cells. Furthermore, we
      found elevated level of staining intensity of ChAT in the pregnant oviduct at day
      13. Using the same ChAT antibody for Western blot analyses, we detected
      immunoreactive bands of MW 69,000 and 46,000 mainly in ampulla, while MW 58,000
      and 30,000 forms were present mainly in infundibulum and isthmus. Furthermore ACh
      was detected by HPLC and fluorimetric methods in oviductal epithelium. In
      conclusion, we show expression of ChAT in oviductal epithelial cells at different
      stages of the oestrus cycle and pregnancy, indicating that these cells can
      synthesize ACh in a cycle-dependent manner. These results suggest as yet
      unexplored roles of epithelial ACh in the oviduct.

PMID- 17024298
TI  - Expression pattern of BMPs during chick limb development.
AB  - In vertebrates, BMPs (bone morphogenic proteins) play critical roles in
      establishing the basic embryonic body plan and are involved in the development of
      a large variety of organs and tissues. Here, we analyzed the expression pattern
      of various BMPs (2, 4, 5 and 7) by whole mount in situ hybridization during chick
      limb development. In limb, expression of BMPs suggests evolutionary conserved
      mechanisms of BMP-dependent differentiation between lower and higher vertebrates.
      During the early developmental stages, BMP-2 and BMP-7 are expressed in the
      posterior distal mesenchyme leaving a less prominent expression anteriorly. BMP-4
      is initially expressed in the anterior mesenchyme and spreads later to the whole
      mesenchyme leaving a stronger expression at the anterior side. From HH-stage 25,
      expression of BMP-4 is observed in the anterior-posterior margins of the limb
      bud. The BMPs 2, 4 and 7 are expressed strongly in the AER, whereas BMP-5 is
      expressed as a weak signal in the distal mesoderm during the early stages of limb
      development. Later from HH-stage 25 onwards, BMP-5 is expressed in the dorsal and
      ventral muscular mass of the developing limb. As digits become identifiable,
      expression of BMPs are observed in the interdigital mesenchyme and can also be
      detected along the contours of the developing phalanges and at the distal tips of
      the digits. All these BMPs are found to be expressed in the developing feather
      buds from day 8 onwards.

PMID- 17024299
TI  - The zebrafish mutation m865 affects formation of dopaminergic neurons and
      neuronal survival, and maps to a genetic interval containing the sepiapterin
      reductase locus.
AB  - The zebrafish mutation m865 was isolated during a large-scale mutagenesis screen
      aimed at identifying genes involved in the development and maintenance of
      subgroups of neurons in the zebrafish central nervous system. The phenotype of
      m865 mutant embryos shows defects in the development of dopaminergic neurons in
      the pretectum and of retinal amacrine cells, as well as abnormal caudal
      dopaminergic cluster in the diencephalon. The effects of the mutation appear not
      to be restricted to dopaminergic neurons, as development of other
      neurotransmitter systems (serotonergic and cholinergic) is impaired as well.
      Furthermore, increased apoptosis is localized to the m865 mutant retina and in
      the optic tectum starting at 24hpf, and may lead to the observed reduced size of
      the mutant head and eye. Early patterning is not affected in m865 mutant embryos,
      and expression of genes known to play a role in dopaminergic cell differentiation
      is normal except for reduced expression of nurr1 in the mutant retina. Thus the
      m865 mutation does not specifically affect dopaminergic neuron development. m865
      was genetically mapped to linkage group 5, and the critical genomic interval
      could be narrowed down to a region of 110 kb, containing four candidate genes.
      For one of these candidate genes, sepiapterin reductase (spr), a requirement for
      neuronal survival has previously been implicated, including dopaminergic neurons.
      Identification of the mutated gene should lead to a more detailed understanding
      of the defects observed in m865 mutant embryos, and potentially could enhance the
      understanding of the development and maintenance of specific dopaminergic
      neuronal populations.

PMID- 17024300
TI  - On periodicity and directionality of somitogenesis.
AB  - It is currently thought that the mechanism underlying somitogenesis is linked to
      a molecular oscillator, the segmentation clock, and to gradients of signaling
      molecules within the paraxial mesoderm. Here, we review the current picture of
      this segmentation clock and gradients, and use this knowledge to critically ask:
      What is the basis for periodicity and directionality of somitogenesis?

PMID- 17024301
TI  - Effects of age on sympathetic innervation of the myenteric plexus and
      gastrointestinal smooth muscle of Fischer 344 rats.
AB  - Loss of myenteric neurons with age is well documented, however little is known
      about age-related changes of the sympathetic innervation of the myenteric plexus
      and gastrointestinal smooth muscle. The goal of the present study, therefore, was
      to evaluate the influence of age on the sympathetic innervation of the myenteric
      plexus throughout the gastrointestinal tract. Ad libitum fed virgin male Fischer
      344 rats at 3, 15-16, 24, and 27-28 months of age were sampled. Whole mounts of
      the stomach, small intestine, and large intestine were processed with an antibody
      to tyrosine hydroxylase (TH). Additionally, some specimens labeled for TH were
      stained for NADPH-diaphorase to selectively label the nitrergic subpopulation of
      neurons in the myenteric plexus. Age-related changes in the TH-positive axons
      occurred as early as 15-16 months and became more pronounced by 27-28 months.
      Changes included markedly swollen axons and terminals and a decrease in the
      intensity of TH staining in some of the surviving processes. Similarly, swollen
      NADPH-diaphorase-positive axons were found in the myenteric ganglia and secondary
      plexus between ganglia in the whole mounts of rats 15-28 months of age, but
      swollen nitrergic axons and dystrophic TH-positive axons were never present in
      the same ganglion or connective. Therefore, in the aged rat, deterioration of the
      sympathetic innervation of the myenteric plexus could be one possible mechanism
      for the age-related decline in gastrointestinal motor function evidenced in the
      elderly.

PMID- 17024302
TI  - The eventful somite: patterning, fate determination and cell division in the
      somite.
AB  - The segmental somites not only determine the vertebrate body plan, but also
      represent turntables of cell fates. The somite is initially naive in terms of its
      fate restriction as shown by grafting and rotation experiments whereby
      ectopically grafted or rotated tissue of newly formed somites yielded the same
      pattern of normal derivatives. Somitic derivatives are determined by local
      signalling between adjacent embryonic tissues, in particular the neural tube,
      notochord, surface ectoderm and the somitic compartments themselves. The correct
      spatio-temporal specification of the deriving tissues, skeletal muscle,
      cartilage, endothelia and connective tissue is achieved by a sequence of
      morphogenetic changes of the paraxial mesoderm, eventually leading to the three
      transitory somitic compartments: dermomyotome, myotome and sclerotome. These
      structures are specified along a double gradient from dorsal to ventral and from
      medial to lateral. The establishment and controlled disruption of the epithelial
      state of the somitic compartments are crucial for development. In this article,
      we give a synopsis of some of the most important signalling events involved in
      somite patterning and cell fate decisions. Particular emphasis has been laid on
      the issue of epithelio-mesenchymal transition and different types of cell
      division in the somite.

PMID- 17024304
TI  - Laparoscopy and collagen metabolism.
AB  - The collagens represent a vital component within the wound healing process and
      physiological scar formation. Therefore, analysing the influence of new operative
      procedures on collagen metabolism is of great surgical interest. As the
      endoscopic technique has, nowadays, become routinely applied for diverse
      abdominal diseases worldwide, we present a review of literature facing its impact
      on collagen biology.

PMID- 17024305
TI  - Hernia disease and collagen gene regulation: are there clues for intervention?
AB  - Collagens belong to the most abundant proteins in the body. After tissue injury,
      a coordinated regulation of collagen gene expression guides the formation of a
      provisional matrix that subsequently evolves into a mature scar with tensile
      strength. In the following, knowledge regarding collagen gene regulation that may
      provide insight into how to specifically address the biological problem of soft
      tissue weakness and recurrent hernia disease is summarized.

PMID- 17024306
TI  - Are collagens the culprits in the development of incisional and inguinal hernia
      disease?
AB  - Incidence curves for the development of inguinal hernia disease and recurrences
      thereof exhibit a linear rise over the years and therefore suggest multi
      factorial underlying causes. Several studies have revealed marked changes in the
      abundance and composition of interstitial collagens in patients with (recurrent)
      hernia diseases, adult groin hernia and incisional hernia. These observations led
      to the hypothesis that hernia formation and the recurrence of incisional hernia
      may be explained by disordered tissue renewal and by abnormal wound healing,
      respectively. Interstitial collagens, owing to their long half-lives and
      biomechanical strength, are most likely critical components of the biological
      system of tissue remodelling. An overview of the literature is provided, and the
      consequences for surgical practice are discussed.

PMID- 17024307
TI  - A complex fistula caused by an eroding pelvic mesh sling.
AB  - Pelvic mesh slings are increasingly used to create abdomino-pelvic partitions.
      This procedure is usually safe and carries low morbidity and mortality rates.
      However, we report a case of a 60-year-old male with a history of an abdomino
      perineal resection for a low rectal carcinoma followed by adjuvant radiotherapy,
      who presented with an entero-vesicle-cutaneous fistula as a result of the
      polypropylene mesh eroding into his small bowel. He had to have a total
      cystectomy, small bowel resection and mesh removal in order to alleviate his
      symptoms.

PMID- 17024308
TI  - Anatomical features of the minor duodenal papilla in pancreas divisum.
AB  - BACKGROUND: Clinical expression of pancreas divisum is often explained as a
      consequence of relative or true stenosis of the minor papilla with dorsal duct
      obstruction. This anatomo-functional study of the minor papilla in pancreas
      divisum has included its topographical, functional and structural features.
      MATERIALS AND METHODS: The study was carried out on 37 human autopsy specimens of
      duodenopancreas, which underwent pancreatography, manometrically controlled
      perfusion and light microscopy. RESULTS: One pancreas divisum was detected in the
      study group. In this case, the distances between the minor and the major papilla
      was 24.0 mm, and between the minor papilla and the superior duodenal flexure 27.4
      mm. The minor papilla was patent when perfused under pressure of 10 mmHg, and its
      light microscopy revealed regular global histological organization with only
      light fibrosis and no cellular atypia. CONCLUSIONS: The structure and position of
      the minor papilla in pancreas divisum did not significantly differ from the ones
      in fused pancreases.

PMID- 17024309
TI  - Study of the cremasteric muscle during erection.
AB  - BACKGROUND: Mechanism of testicular elevation during erection is not known. We
      investigated the hypothesis that erection evokes reflex cremasteric muscle (CM)
      contraction which effects testicular elevation. METHODS: Electromyographic (EMG)
      response of CM to erection was recorded in 26 healthy volunteers (age 36.7 +/-
      6.8 SD years). Erection was induced by intracavernosal injection of alprostadil.
      CM response was tested before and after individual glans penis (GP) and CM
      anesthetization. RESULTS: The CM exhibited resting electric activity of mean
      amplitude of 74.8 +/- 6.3 microV which, on erection, increased to 486.6 +/- 36.8
      microV (P < 0.001). Response was momentary. Anesthetization of erect GP did not
      effect increase of CM EMG activity, while bland gel did. Anesthetized CM did not
      respond to GC erection while saline infiltrated did. CONCLUSIONS: The CM appears
      to contract during erection through a reflex which we call 'peno-cremasteric
      reflex'. CM contraction assumingly elevates testicle and support cord veins; it
      may effect testicular compression, thus expressing its secretions into vas
      deferens.

PMID- 17024310
TI  - Variant origin of superior thyroid artery, occipital artery and ascending
      pharyngeal artery from a common trunk from the cervical segment of internal
      carotid artery.
AB  - We report a case of variant origin of superior thyroid artery (STA), occipital
      artery (OA) and ascending pharyngeal artery (APA) from the cervical segment of
      internal carotid artery (ICA) in a 63-year-old male patient, who presented with
      acute subarachnoid hemorrhage. Four-vessel angiography showed asymptomatic
      occlusion of ICA giving origin to the anomalous branches. There was common origin
      of the STA and the OA. The APA originated from the OA. We did not find any other
      description in the literature on variant origin of STA from the cervical segment
      of ICA in the presence of a well-developed external carotid artery.

PMID- 17024311
TI  - Effect of +36T>C in intron 1 on the glutamine: fructose-6-phosphate
      amidotransferase 1 gene and its contribution to type 2 diabetes in different
      populations.
AB  - Glutamine: fructose-6-phosphate amidotransferase 1 (GFPT1) acts as a rate
      limiting enzyme in the hexosamine biosynthetic pathway, which is an alternative
      branch of glucose metabolism. To evaluate GFPT1 as a susceptibility gene to type
      2 diabetes, we surveyed the polymorphisms related with the gene function of GFPT1
      and assessed its contribution to type 2 diabetes with a case-control association
      study. Screening of the 5'-flanking and all coding regions of GFPT1 revealed
      eight polymorphisms, one in the 5'-flanking region, one synonymous polymorphism
      in exon 8, five in introns and one in 3'-UTR, but no mis-sense or non-sense
      polymorphism. With in silico simulation, a putative promoter region was
      apparently predicted between 1 kb upstream and 1 kb downstream of the start
      codon. In this region, +36T>C polymorphism was located on the GC box sequence in
      intron 1, and its functional effect on promoter activity was confirmed by
      luciferase reporter assay, introducing a new functional polymorphism of the GFPT1
      gene. To examine its association with type 2 diabetes, we analyzed 2,763 Japanese
      (1,461 controls and 1,302 cases) and 330 Caucasians (190 controls and 140 cases).
      One possible association of +36T>C was observed in Caucasians, but no association
      of polymorphisms including +36T>C in intron 1 or haplotypes was observed in
      Japanese. Although we could not completely rule out a contribution to specific
      sub-groups or other populations, genetic variation of GFPT1 is unlikely to have a
      major role in the susceptibility to type 2 diabetes in Japanese.

PMID- 17024312
TI  - Genetic structural differences between responders and non-responders to
      interferon therapy for chronic hepatitis-B patients.
AB  - Interferon-alpha therapy has become a main stay of treatment for hepatitis-B
      patients. The sustained remission rates are around 30%, and the factors
      determining response are poorly defined. Our study aimed to search for the
      genetic differences between responder and non-responder patients. We have found
      13 short tandem repeat markers (STR) that display different allele and/or
      genotype frequency between the two patient groups. Eleven out of 13 STR markers
      were selected to perform principal component analysis and hierarchical
      clustering. The study subjects could be further divided into six groups based on
      their genetic similarity, which correlated with the drug response rate. In
      conclusion, this pilot study has developed a new approach to identify genetic
      markers that allows us to predict the drug response in hepatitis B patients. Our
      study utilizing STR markers may provide an alternative approach to the utilized
      SNP markers in pharmacogenetic study.

PMID- 17024313
TI  - Replication of the association of the aspartic acid repeat polymorphism in the
      asporin gene with knee-osteoarthritis susceptibility in Han Chinese.
AB  - A genetic association of osteoarthritis (OA) and functional polymorphisms in the
      aspartic acid (D) repeat of the asporin gene was reported in Japanese and
      European Caucasians; however, the results were controversial. Our objective was
      to evaluate whether the D repeat polymorphism was associated with knee OA in Han
      Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered
      from primary symptomatic knee OA with radiographic confirmation and in 454 age
      matched controls, and the allelic association of the repeat was examined.
      Frequencies of the D13 and D14 alleles were similar to those of Japanese, but
      different from those of European Caucasians. The D14 allele was significantly
      over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence
      interval 1.32-3.15). D14 was more frequent in early-onset patients than in late
      onset patients (P=0.043) and the age at onset in patients with D14 was earlier
      (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA
      susceptibility was replicated in Han Chinese. This was the first instance that
      association of the OA susceptibility gene was definitely replicated between
      different ethnic groups.

PMID- 17024314
TI  - A Japanese case of SCA14 with the Gly128Asp mutation.
AB  - Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant
      cerebellar ataxias caused by mutations in the protein kinase Cgamma gene (PRKCG).
      We have identified a Japanese patient with SCA14 who carried the Gly128Asp
      mutation in PRKCG. She first noticed gait unsteadiness at around age 42, and then
      her gait ataxia worsened very slowly for more than 20 years. At age 62, she was
      still ambulatory, although cerebellar ataxia was clinically evident. She is the
      second patient identified with the G128D mutation. Both patients with this
      mutation showed pure cerebellar ataxia. With only two families with SCA14 found
      in Japan prior to this study, the clinical features and disease-causing mutations
      in PRKCG are heterogeneous in the same ethnic background.

PMID- 17024316
TI  - Identification of chromosomal regions linked to premature myocardial infarction:
      a meta-analysis of whole-genome searches.
AB  - Myocardial infarction (MI) is a complication of coronary artery disease and the
      leading cause of death in the Western world. MI is considered a distinct
      phenotype with an increased genetic component for its premature type. MI's exact
      inheritance pattern is still unknown. Genome searches for identifying
      susceptibility loci for premature MI produced inconclusive or inconsistent
      results. Thus, a genome search meta-analysis (GSMA) was applied to available
      genome search data on premature MI. GSMA is a non-parametric method to identify
      genetic regions that rank high, on average in terms of linkage statistics across
      genome searches unweighted or weighted by study size. The significance of each
      region's average and heterogeneity, unadjusted or adjusted by neighbouring
      average simulated ranks, was calculated using a Monte Carlo test. The meta
      analysis involved five genome searches in Caucasians. Eight regions (6p22.3
      6p21.1, 14p13-14q13.1, 13q33.1-13q34, 5p15.33-5p15.1, 8q13.2-8q22.2, 1p36.21
      1p35.2, 12q24.31-12q24.33, 8q24.21-8q24.3) were found to have significant average
      rank by either unweighted or weighted analyses. In addition, region 8q24.21
      8q24.3 produced significant low heterogeneity (P (unadjusted)=0.03 and P
      (adjusted)=0.05). Four regions (6p22.3-6p21.1, 14p13-14q13.1, 8q13.2-8q22.2,
      8q24.21-8q24.3) were not identified by the individual studies. The meta-analysis
      suggests that these four regions should be further investigated for genes that
      confer susceptibility to MI.

PMID- 17024315
TI  - Association study of COL9A2 with lumbar disc disease in the Japanese population.
AB  - Lumbar disc disease (LDD) is a common musculo-skeletal disease with strong
      genetic determinants. In a Finnish population, a single nucleotide polymorphism
      (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes
      the alpha2 (IX) chain of type IX collagen, has been reported to associate with
      LDD. However, replication studies in different populations have produced
      controversial results. To further investigate the association of COL9A2 with LDD
      in Japanese, we examined SNPs in COL9A2, including Trp2, in 470 LDD patients
      (mean age 35) along with 658 controls (mean age 48). We identified a total of 43
      sequence variations in COL9A2. Nine SNPs, including Trp2, were selected and
      genotyped. After Bonferroni's correction, none of these SNPs showed association.
      Unlike observations in the Finnish population, Trp2 was common in Japanese, and
      no association with LDD was apparent. However, we did see association of a COL9A2
      specific haplotype with LDD (P=0.025; permutation test); this association is more
      significant in patients with severe lumbar disc degeneration (P=0.011). Thus, the
      association of Trp2 with LDD was not replicated, but COL9A2 susceptibility
      allele(s) other than Trp2 may be present in Japanese LDD.

PMID- 17024317
TI  - Multislice CT pulmonary findings in Behcet's disease (report of 16 cases).
AB  - Pulmonary artery aneurysm is the best-defined type of pulmonary disease in
      Behcet's disease (BD) with an important morbidity and mortality. The objective of
      this study was to assess the contribution of high-resolution dynamic chest CT
      imaging for one of the most serious aspects of BD: pulmonary artery aneurysm and
      other pulmonary parenchymal involvement. Sixteen BD patients were recruited for
      this study, (14 men, 87.5%, and 2 women, 12.5%). All patients fulfilled the 1990
      American College of Rheumatology criteria for classification of BD [International
      Study Group for Behcet's Disease, Lancet 335:1078-1080, (1990)]. All patients
      underwent thorough history taking, full clinical examination, and routine
      laboratory investigations. Plain chest X-rays and pulmonary CT angiography were
      performed on all patients in an attempt to assess the pulmonary vasculature and
      lung parenchyma. Pulmonary vascular abnormalities were as follows: pulmonary
      artery aneurysms of varying sizes in nine patients (56.3%), main pulmonary artery
      ectasia in two patients (12.5%), pulmonary artery embolism in two patients
      (12.5%), venacaval thrombosis in seven patients (43.8%), and pulmonary venous
      varices in four patients (25%). Pulmonary parenchymal abnormalities were as
      follows: three patients (18.8%) with mild central bronchiectasis, one patient
      (6.3%) with atelectasis, one patient (6.3%) with subpleural nodule, and four
      patients (25%) with interstitial lung disease. Eight of the male patients were
      smokers. Multislice CT is useful in demonstrating the entire spectrum of thoracic
      manifestations of BD. Multislice CT is noninvasive and provides excellent
      delineation of the vessel lumen and wall and perivascular tissues, as well as
      detailed information concerning the lung parenchyma, pleura, and mediastinal
      structures.

PMID- 17024318
TI  - Plasma homocysteine status in patients with ankylosing spondylitis.
AB  - Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B
      vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an
      independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and
      peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid
      arthritis were reported to be associated with hyperhomocysteinemia. This study
      was aimed to evaluate the changes of plasma Hcy level before and after
      sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One
      hundred and two patients with AS and ten normal controls were enrolled in the
      cross-sectional case-control study. Fasting plasma Hcy levels were determined by
      ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease
      activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease
      was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For
      those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily
      supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks
      were also tested for the efficacy. Plasma Hcy level increased significantly in AS
      patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7,
      p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared
      with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/-
      2.6 micromol/l). No correlation between disease activity and plasma Hcy level was
      found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg
      can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007).
      Plasma homocysteine level did significantly increase in AS patients under
      sulfasalazine or MTX treatment. B-vitamins should be considered as a routine
      supplementation for patients who underwent sulfasalazine and/or MTX treatment.
      Further longitudinal studies are required to confirm the conclusions.

PMID- 17024319
TI  - In vitro behavior of Porfimer sodium and Talaporfin sodium with high intensity
      pulsed irradiation.
AB  - We studied pulse energy density dependence of two distinctive clinical
      photosensitizers, Porfimer sodium and Talaporfin sodium, in terms of oxygen
      consumption, photodegradation in these photosensitizer solutions, and rat
      prostate cancer cell line photocytotoxicity. The transient transmittances during
      the pulsed irradiation to these photosensitizer solutions were measured with the
      pulse energy densities ranging from 0.31 to 31 mJ/cm2. We revealed that
      Talaporfin sodium was easier to produce absorption saturation than Porfimer
      sodium. The significant suppression of Talaporfin sodium mediated oxygen
      consumption, photodegradation, and photocytotoxicity which were observed with
      pulse energy densities increasing from 0.5 to 10 mJ/cm2. This result could be
      mainly attributed to absorption saturation. On the other hand, Porfimer sodium
      did not display significant absorption saturation with the pulse energy densities
      ranging from 0.31 to 31 mJ/cm2. The photodegradation mechanism for Porfimer
      sodium changed at high pulse energy density. This phenomenon might accelerate the
      photodegradation and cause the photocytotoxicity suppression.

PMID- 17024320
TI  - Raman spectroscopy of parathyroid tissue pathology.
AB  - Primary hyperparathyroidism (HPT) in 80% of patients is due to a solitary
      parathyroid adenoma, while in 20% multigland pathology exists, usually
      hyperplasia [Scott-Coombes, Surgery, 21(12):309-312, 2003]. Despite recent
      advances in minimally invasive parathyroidectomy, better preoperative
      localisation techniques and intraoperative parathyroid hormone (PTH) monitoring,
      a 4% failure rate [Grant CS, Thompson G, Farley D, Arch Surg, 140:47-479, 2005]
      persists making accurate differentiation between adenomas and hyperplasia of
      prime importance. We investigated the ability of Raman spectroscopy to accurately
      differentiate between parathyroid adenomas and hyperplasia. Raman spectra were
      measured at defined points on the parathyroid tissue sections using a bench-top
      microscopy system. Multivariate analysis of the spectra was carried out to
      construct a diagnostic algorithm correlating spectral results with the
      histopathological diagnosis. A total of 698 spectra were analysed. Principal
      component (PCA)-fed linear discriminant analysis (LDA) used to construct a
      diagnostic algorithm. Detection sensitivity for parathyroid adenomas was 95% and
      hyperplasia was 93%. These preliminary results indicate that Raman spectroscopy
      is potentially an excellent tool to differentiate between parathyroid adenomas
      and hyperplasia.

PMID- 17024321
TI  - Coloseminal vesicle fistula: report of a case and review of the literature.
AB  - Despite their anatomic proximity, communication between the colorectum and
      seminal vesicle is an uncommon event. We describe the first reported case of a
      fistula between the colon and seminal vesicle as a complication of
      diverticulitis. This case report is followed by a literature review of other
      reported cases of fistula formation between the seminal vesicle and the colon.

PMID- 17024322
TI  - Long-term outcome of argon plasma ablation therapy for bleeding in 100
      consecutive patients with colonic angiodysplasia.
AB  - PURPOSE: Angiodysplasia is a frequent cause of colonic bleeding. Argon plasma
      coagulation was reported to be useful in endoscopic hemostasis. However, the long
      term outcomes have been poorly evaluated. This study was designed to assess the
      long-term outcomes of bleeding patients with colonic angiodysplasia treated by
      argon plasma coagulation. METHODS: A cohort of 100 patients with gastrointestinal
      bleeding caused by colonic angiodysplasia was studied prospectively. The
      endoscopic intervention was considered successful if there was no further overt
      bleeding and hemoglobin concentration was stabilized (primary end point).
      Secondary end points were the requirement of blood transfusions, the need for
      surgery, bleeding-related mortality, and overall mortality. RESULTS: Overt
      bleeding resolved and hemoglobin levels were stabilized without transfusions or
      iron therapy in 85 of 100 patients (85 percent) after a median follow-up of 20
      (range, 6-62) months. Transfusion requirements ceased in 90 percent of patients
      and only one required surgery. No patient died because of hemorrhage. In the
      subgroup of patients with anemia, mean hemoglobin levels increased from 9.3
      (range, 5.5-12.2) g/dl before treatment to 12.6 (range, 7.4-16.7) g/dl after
      treatment (P < 0.01). The probability of remaining free of rebleeding at one and
      two year follow-up was 98 percent (95 percent confidence interval, 96-100) and 90
      percent (95 percent confidence interval, 83-97), respectively. Among 118
      procedures, only two complications were observed (1.7 percent). CONCLUSIONS:
      Endoscopic argon plasma ablation therapy is useful in the management of bleeding
      from colonic angiodysplasia.

PMID- 17024323
TI  - Genome analysis of a severe and a mild isolate of Papaya ringspot virus-type W
      found in Brazil.
AB  - Papaya ringspot virus-type W (PRSV-W) is one of the most economically threatening
      viruses of cucurbits in Brazil. Premunization is one of the most effective PRSV
      control measures currently applied in squash and zucchini crops. PRSV-W-1, a mild
      and premunizing strain of PRSV has been successfully used to protect cucurbits
      against both the severe PRSV-W-C strain and other Brazilian PRSVs. To aid in
      understanding the mechanism by which PRSV-W-1 premunization operates, the
      complete genome sequences of PRSV-W-1 and PRSV-W-C were determined. PRSV-W-1 had
      a genome size of 10,332 nucleotides, whereas indels within the coat protein
      encoding gene meant that the genome size of PRSV-W-C was six nucleotides shorter
      than that of the mild strain. The genomes of the two strains shared 94.63%
      nucleotide sequence identity, with the 5' UTR and P1 being the most variable
      regions, and the coat protein and 3' UTR being the most conserved. Rigorous
      recombination analysis revealed that neither PRSV-W-1 nor PRSV-W-C was obviously
      recombinant, there was significant evidence that many other fully sequenced PRSV
      genomes were recombinant.

PMID- 17024324
TI  - Structural brain abnormalities in early onset first-episode psychosis.
AB  - BACKGROUND: Brain morphometry in children and adolescents with first-episode
      psychosis offer a unique opportunity for pathogenetic investigations. METHODS: We
      compared high-resolution 3D T1-weighted magnetic resonance images of the brain in
      29 patients (schizophrenia, schizotypal disorder, delusional disorder or other
      non-organic psychosis), aged 10-18 to those of 29 matched controls, using
      optimized voxel-based morphometry. RESULTS: Psychotic patients had frontal white
      matter abnormalities, but expected (regional) gray matter reductions were not
      observed. Post hoc analyses revealed that schizophrenia patients (n = 15) had
      significantly larger lateral ventricles as compared to controls. Duration and
      dose of antipsychotics correlated negatively with global gray matter volume in
      minimally medicated patients (n = 18). CONCLUSION: Findings of white matter
      changes and enlarged lateral ventricles already at illness onset in young
      schizophrenia spectrum patients, suggests aberrant neurodevelopmental processes
      in the pathogenesis of these disorders. Gray matter volume changes, however,
      appear not to be a key feature in early onset first-episode psychosis.

PMID- 17024325
TI  - Movement disorders: neurodevelopment and neurobehavioural expression.
AB  - Braak and co-workers have recently shown that movement disorders such as
      Parkinson's disease develop progressively over years with early neuronal losses
      in brainstem regions caudal to the substantia nigra. The relevance of this
      finding to notions of comorbidity between movement disorders and psychiatric
      symptoms was recognised at the recent meeting concerning, "Implications of
      Comorbidity for the Etiology and Treatment of Neuropsychiatric Disorders" held in
      Oct. 2005 in Mazagon, Spain. The identification of stages in the early
      development of neurodegenerative disorders appeared to unify multiple, diverse
      findings. These included: novel therapeutic innovations for Parkinson's disease,
      Alzheimer's disease and depression in the aged; the neurochemical ontogeny of
      drug-induced oral dyskinesias; the types of chemical agents abused in
      neuropsychiatric states; postnatal iron overload effects upon the functional and
      interactive role of dopaminergic and noradrenergic pathways that contribute to
      the expression of movement disorders; and the spectrum of motor symptoms
      expressed in schizophrenia and attention deficit hyperactivity disorder and the
      eventual treatment of these disorders. A continued focus on a number of
      neuropsychiatric diseases as progressive disorders may lead to further advances
      in understanding their etiology and in developing better therapeutics.

PMID- 17024326
TI  - Voxel-based morphometry indicates relative preservation of the limbic prefrontal
      cortex in early Huntington disease.
AB  - In Huntington disease (HD), both the genetic defect and mutant gene product
      huntington are known but the exact mechanisms that lead to neuronal loss are
      poorly understood. Until now, the distribution of tissue loss throughout the
      brain has been investigated intensively. Here we searched for areas that,
      antipodal to the striatum, display grey-matter (GM) preservation. We performed
      high resolution T1-weighted magnetic resonance imaging and voxel-based
      morphometry in 46 patients in early HD and 46 healthy controls. We applied an
      analysis of covariance (ANCOVA) model with the total GM volume of each
      participant as covariate. In accordance with earlier reports, group comparisons
      revealed GM decrease in the striatum, insula, and thalamus as well as in
      dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal
      cortex displayed GM preservation. Our findings support hypotheses that postulate
      differential involvement of frontosubcortical circuits in the pathophysiology of
      HD.

PMID- 17024328
TI  - Motor cortex inhibitory circuits in dementia with Lewy bodies and in Alzheimer's
      disease.
AB  - To determine whether a peculiar neurophysiological profile may contribute to
      characterize dementia with Lewy bodies (DLB) vs. Alzheimer disease (AD), we used
      transcranial magnetic stimulation to examine the excitability of two different
      inhibitory systems of the motor cortex, short latency intracortical inhibition
      (SICI) and short latency afferent inhibition (SAI) in 10 patients with DLB, in 13
      patients with AD and in 15 healthy subjects. SICI and SAI were significantly
      reduced in AD patients, while both were not significantly different from the
      controls in DLB patients. The differential pattern of SICI and SAI exhibited by
      AD vs. DLB may have diagnostic significance in discriminating DLB from AD.
      Furthermore, this technique may help to clarify the pathophysiological entity of
      DLB; since SAI is a cortical phenomenon that depends on central cholinergic
      activity, our findings suggest that the mechanisms of cholinergic depletion in
      DLB may be different from that in AD, while normal SICI may reflect a less
      pronounced dysregulation of the intracortical GABAergic inhibitory circuitries in
      DLB.

PMID- 17024327
TI  - Receptor-receptor interactions involving adenosine A1 or dopamine D1 receptors
      and accessory proteins.
AB  - The molecular basis for the known intramembrane receptor-receptor interactions
      among heptahelical receptors (G protein coupled receptors, GPCR) was postulated
      to be heteromerization based on receptor subtype specific interactions between
      different types of homomers of GPCR. Adenosine and dopamine receptors in the
      basal ganglia have been fundamental to demonstrate the existence of receptor
      heteromers and the functional consequences of such molecular interactions. The
      heterodimer is only one type of heteromeric complex and the evidence is equally
      compatible with the existence of higher order heteromeric complexes, where also
      adapter proteins such as homer proteins and scaffolding proteins can exist,
      assisting in the process of linking the GPCR and ion channel receptors together
      in a receptor mosaic that may have special integrative value and may constitute
      the molecular basis for learning and memory. Heteromerization of D(2) dopamine
      and A(2A) adenosine receptors is reviewed by Fuxe in another article in this
      special issue. Here, heteromerization between D(1) dopamine and A(1) adenosine
      receptors is reviewed. Heteromers formed by dopamine D(1) and D(2) receptors and
      by adenosine A(1) and A(2A) receptors also occur in striatal cells and open new
      perspectives to understand why two receptors with apparently opposite effects are
      expressed in the same neuron and in the nerve terminals. The role of accessory
      proteins also capable of interacting with receptor-receptor heteromers in
      regulating the traffic and the molecular physiology of these receptors is also
      discussed. Overall, the knowledge of the reason why such complex networks of
      receptor-receptor and receptor-protein interactions occur in striatal cells is
      crucial to develop new strategies to combat neurological and neuropsychiatric
      diseases.

PMID- 17024329
TI  - Effects of an inhibitor of alpha-secretase, which metabolizes the amyloid peptide
      precursor, on memory formation in rats.
AB  - Intracortical administration of 10(-4) M batimastat, a specific inhibitor of
      alpha-secretase (a metalloproteinase which cleaves the amyloid peptide
      precursor), decreased the number of correct runs in a single-level eight-arm maze
      to 92.78 +/- 1.03% compared with baseline (p < 0.01) within 60 min. However,
      injection of batimastat into the cerebral cortex of animals during the early
      postnatal period (days 5 and 7 of life) led to impaired orientation in the simple
      single-level maze when these adults reached adulthood (90.92 +/- 2.21% correct
      runs, p < 0.001) as compared with controls. The data obtained here provide
      evidence for the important role of alpha-secretase in memory processes. The
      possible role of alpha-secretase in memory processes and the pathogenesis of
      Alzheimer's disease is discussed.

PMID- 17024330
TI  - Biochemical markers of apoptosis in different parts of the brain during learning.
AB  - Caspase-3 activity and the levels of DNA fragments of 200-600 and >4000 b.p. were
      estimated in the cerebellar vermis, the hippocampus, and the prefrontal cortex of
      the brains of adult rats four and 24 months after training to extinction of the
      acoustic startle reaction and conditioned fear. Differently timed changes in the
      levels of biochemical markers of apoptosis were seen to different extents in
      these brain areas after training. These changes were characterized by a decrease
      in caspase-3 activity in the cerebellar vermis and the hippocampus, with
      decreases in DNA fragmentation in the hippocampus and cerebral cortex and
      increases in measures of programmed cell death in the hypothalamus. These
      experimental data support the view that the apoptosis of cells in the mature
      brain is involved in the mechanisms of learning and memory.

PMID- 17024331
TI  - General laws for the formation of the state of monotony.
AB  - Experimental studies have demonstrated that the formation of the state of optimum
      working ability in conditions of monotonous activity is associated with a
      decrease (compared to the rest state) in the level of "preventive" arousal of the
      CNS, manifest on the EEG as an increase in the power of slow rhythms on the
      background of a selective increase in the level of coherence at frequencies in
      the alpha rhythm in the caudal areas of the cortex. Prolonged exposure to
      monotonous conditions leads to increases in the power of slow (theta and
      alpha(1)) and beta frequencies in the EEG spectrum without marked changes in the
      level of coherence. Our results, along with published data, were used to propose
      the hypothesis that unlike the basic states of the sleep-waking cycle (sleep,
      rest, active waking, etc.), the state of monotony lacks intrinsic ("built-in")
      self-regulatory mechanisms; this results in instability in the operation of the
      regulatory systems of the brain. This leads to the appearance of marked
      periodicity in changes in both the functional state of the CNS and the quality of
      work performed by humans.

PMID- 17024332
TI  - A common system of sparsely-branched projection (reticular) NADPH-diaphorase
      neurons in formations of densely-branched cells in the human forebrain.
AB  - Morphometric studies of human forebrain formations composed of densely branched
      cells - the entorhinal cortex, the basolateral amygdala, the nucleus accumbens,
      the striatum, and the dorsal thalamus - were performed using nine parameters,
      with statistical analysis of the resulting data; measurements addressed the major
      projection-type densely branched and sparsely branched reticular neurons
      (scattered reticular and marginal reticular cells of the dorsal thalamus) stained
      by the Golgi method and with NADPH-diaphorase. Scattered reticular cells in the
      various formations showed no differences in any of the nine measures, while there
      were significant differences (in 5-7 measures, apart from one comparison, where
      there were differences in two measures) in their major projection-type densely
      branched cells. Scattered reticular and main projection-type densely branched
      neurons in each formation differed in terms of 7-9 measures. In endbrain
      formations, scattered reticular neurons contained NADPH-diaphorase; in the dorsal
      thalamus, only intermediate marginal reticular neurons were NADPH-diaphorase
      positive. Thus, these human formations contained a common system of ancient
      integrative NADPH-diaphorase-containing reticular cells. Our results, along with
      published data, show these to be projection-type cells with projections to layers
      V and VI of the neocortex, which suggests that they have modulatory influences on
      its descending systems.

PMID- 17024333
TI  - The effects of the experience of forming visual images on the spatial
      organization of the EEG.
AB  - The spatial organization of biopotentials in the cerebral cortex of 23 subjects
      who were students at the Faculty of Graphic Arts ("professionals") as well as 39
      subjects lacking systematic experience of visual images ("non-professionals") was
      compared with the aim of identifying EEG correlates of the experience of visual
      images (image formation) in humans. Changes in measures of the spatial
      organization of biopotentials (spatial synchronization, spatial disordering,
      coherence, and spectral power) were analyzed as subjects mentally composed visual
      images consisting of two simple graphic elements - right angles and oblique
      lines. The total number of image elements increased in each of four sequential
      tasks, from a number which could be analyzed at the conscious level (4-7
      elements) to a number exceeding analysis at the conscious level (8-16).
      Intergroup differences, particularly increases in the spatial disordering of
      biopotentials (non-linear processes), were detected when large numbers of
      elements were used (tasks 3 and 4). This measure increased more markedly in
      professionals than in non-professionals. Changes were significant in the anterior
      areas of the right hemisphere. Spatial synchronization of biopotentials (linear
      processes) increased in non-professionals in the posterior areas of the right
      hemisphere. Coherence and spectral power increased in professionals in a larger
      number of narrow-band EEG frequency subranges than in non-professionals. These
      data show that experience of visual imagery results in a more complex
      neurodynamic process during the activity, with non-linear dynamics and a
      multitude of EEG resonance systems at different frequencies.

PMID- 17024334
TI  - The roles of various projection areas of the motor cortex in the reorganization
      of the natural coordination of head and forelimb movements in dogs.
AB  - A food-related operant reaction was developed in dogs, in which animals had to
      maintain tonic elevation of the forelimb to hold a bowl while eating with the
      head tilted towards the feeder. The acquisition of this reaction involved
      rearrangement of the natural coordination of head and limb movements which
      appeared at an early stage of training of the dogs. Forelimb elevation was
      initially accompanied by anticipatory raising of the head, while lowering of the
      head led to lowering of the elevated limb. Limb elevation could only be
      maintained in the posture in which the head was raised. The new coordination
      required for obtaining food, contrary to the innate coordination and consisting
      of tonic elevation of the limb with the head lowered, could only be achieved as a
      result of training. Previous studies have established that lesioning of the
      primary motor cortex (MI) in the hemisphere contralateral to the working limb
      leads to stable impairment of the learned coordination, with regression to the
      initial coordination. The present report describes studies of the effects of
      local lesions of various projection areas of MI on performance of the learned
      coordination. Dogs which had acquired the learned operant reaction requiring the
      new head/limb coordination showed impairment only after lesioning of the
      representation area of the working limb in the MI; lesioning of the
      representation area of the head had no such effect.

PMID- 17024335
TI  - The role of motivation in the performance of conditioned reflex switching of a
      maze skill in response to substitution of food reward quality in ants of the
      species Myrmica rubra.
AB  - The characteristics of learning in ants - active Myrmica rubra foragers - were
      studied in a maze at different levels of colony carbohydrate food need with
      reinforcement consisting of carbohydrate (sugar syrup) or protein (pupae of
      Lasius niger ants). Measures of the maze skill during learning reinforced with
      syrup were somewhat worse than those during learning reinforced with pupae,
      especially in terms of time-based measures. Ants were able to modify the acquired
      conditioned reflex reaction when the quality of reinforcement changed. At high
      levels of food need (" hungry" colony), substitution of syrup with larvae and
      vice versa was followed by transformation of the previously formed skill; this
      occurred at both experimental periods (training and testing). At low levels of
      motivation ("sated colony"), the optimized maze habit formed with protein
      reinforcement was replaced in the test with carbohydrate reinforcement by a
      "stochastic," unoptimized behavior with a dominance of investigative activity.
      These experiments demonstrated that conditioned reflex switching can occur in
      higher social insects - ants - in which the different forms depend on the level
      of colony need for food and, respectively, on the level of social food-related
      motivation of forager ants. The special importance of using the switch activating
      the corresponding motivational system before changing the reinforcement food
      quality is emphasized.

PMID- 17024336
TI  - Learning and memory: traditional and systems approaches.
AB  - The aims of the present work were to consider the characteristics of learning and
      memory from the point of view of a systems approach and to compare this view with
      the traditional approach. Neuron activity is regarded not as a response to the
      synaptic influx resulting in excitation but as a means of altering the cell's
      relationship with its environment, whose "action" is to eliminate discordance
      between the cell's "needs" and its microenvironment. The neuronal mechanisms of
      learning and consolidation of memory are regarded not as formation of a stable
      increase in the efficiency of synaptic transmission in circuits of connected
      neurons, but as a system genesis event which confers new system specializations
      on neurons which do not have to be directly connected synaptically. The roles of
      the processes of selection, reconsolidatory modification of previously formed
      memories, gene activation, neurogenesis, and apoptosis in systems genesis
      occurring both in normal and pathological conditions are discussed. Individual
      development is regarded as a sequence of system genesis events. The systems
      approach is applied to the phenomenon of long-term potentiation. In conclusion, a
      scheme including different types and stages of memory formation is presented.

PMID- 17024338
TI  - Structural transformations in sympathetic ganglia and the thoracic part of the
      vagus nerve in conditions of gravitational overloading.
AB  - The aim of the present work was to undertake a complex of studies of structural
      transformations in the anterior thoracic ganglia of the sympathetic trunk and the
      thoracic part of the vagus nerve after acute and chronic gravitational
      overloading (GOL). Studies were performed on 28 white mongrel male rats aged 8-21
      weeks. Animals of series I (acute GOL) were rotated in a centrifuge on one day
      (three rotation sessions with two 20-min breaks, giving a total rotation time of
      31 min). Animals of series II (chronic GOL) were rotated in an alternating two
      week regime for 13 weeks (total rotation time 20 h 9 min). Rotation was performed
      in the craniocaudal direction with overloads of 4-6 g. Intact rats served as
      controls. Histological, electron microscopic, and morphometric analyses were
      performed. Acute GOL produced mainly reversible reactive changes in the anterior
      thoracic nodes of the sympathetic trunk and thoracic part of the vagus nerve,
      probably induced by unusual combinations of afferent spike activity of unusual
      strength, this probably being one of the causes of impairments seen after
      rotation. Chronic GOL was followed by the development of mainly destructive and
      compensatory-adaptive processes, characterized by the destruction of
      mitochondrial cristae, vacuolization of neuron cytoplasm, and degradation of
      interneuronal synapses. These changes were probably due to the development of
      hypoxia, which leads to interneuronal synaptic blockade in sympathetic ganglia.
      These structural transformations demonstrate the involvement of both the
      sympathetic and parasympathetic compartments in responses to acute and chronic
      GOL, providing evidence of the generalization of adaptive processes in the
      autonomic nervous system.

PMID- 17024337
TI  - Structural organization, neurochemical characteristics, and connections of the
      reticular nucleus of the thalamus.
AB  - This review analyzes current concepts of the structural organization and
      ultrastructure of the reticular nucleus of the thalamus (RNT) and the
      neurochemical characteristics of its neurons. The topography, cytoarchitectonics,
      and neuronal organization of this nucleus are considered in detail, as are
      questions of its neurogenesis. Neurochemical data clarifying the representation
      of neurotransmitter systems in the RNT and data on neuropeptides synthesized in
      its neurons are systematized. The complex ultrastructural organization of the RNT
      is characterized in terms of recent data from state-of-the-art immunocytochemical
      methods allowing localization of glutamatergic and GABAergic receptors on
      synaptic elements. Data on the afferent and efferent connections of the RNT
      demonstrate its influences on various parts of the brain and the specific
      features of its interactions with cortical formations.

PMID- 17024339
TI  - Non-specific brain systems and the rehabilitation of children with cerebral
      palsy.
AB  - Prolonged observations of 157 children with spastic forms of childhood cerebral
      palsy (CCP) were used to construct a mathematical regression model for motor
      development in relation to the severity of the course and outcome of the
      condition. Mathematical relationships were established reflecting
      dysneuroontogenesis of the suprasegmental regulatory systems. Data obtained from
      complex electroencephalogram and electroneuromyogram studies, along with
      assessments of autonomic nervous system function, demonstrated a role for intra
      and intersystem disintegration of the limboreticular complex in decreases
      adaptive capacity and rehabilitation potential of patients with CCP. This was
      used to identify the principles of a pathogenetically based adaptive-regulatory
      approach to the rehabilitation of this category of patients, based on the need to
      correct the functional state of non-specific brain systems to create the
      neurodynamic suprasegmental and segmental adaptive-energetic and adaptive
      immunoregulatory prerequisites for forming and supporting specific psychomotor
      functions.

PMID- 17024340
TI  - Effects of local infusions of apomorphine on the extracellular citrulline level
      in the striatum: Involvement of D1 and D2 dopamine receptors.
AB  - Studies using vital microdialysis and high-performance liquid chromatography
      showed that local infusion of the NO synthase inhibitor N-nitro-L-arginine (1 mM)
      into the striatum decreased, while infusion of the dopamine receptor agonist
      apomorphine (100 microM) increased the level of citrulline (a side product of
      nitric oxide synthesis) in the intercellular space of this structure in Sprague
      Dawley rats. The increase in the citrulline level induced by infusions of
      apomorphine was completely prevented by local infusions of N-nitro-L-arginine (1
      mM) and raclopride (10 microm), a dopamine D2 receptor blocker, but not by
      infusion of SCH-23390 (50 microm), a dopamine D1 receptor blocker. These data
      suggest that the increase in extracellular citrulline in the striatum induced by
      dopaminergic stimulation results from local increases in NO synthase activity and
      that this effect involves D2, but not D1 dopamine receptors.

PMID- 17024341
TI  - Interhemisphere connections of the visual cortex in cats with bilateral
      strabismus.
AB  - The distribution of retrograde labeled callosal cells after microiontophoretic
      application of horseradish peroxidase into individual cortical columns in fields
      17 and 18 was studied in cats reared with bilateral strabismus (with an angle of
      eye deviation of 10-35 degrees ). The area containing labeled cells was located
      asymmetrically in relation to the position of the injected column in the opposite
      hemisphere. Some of the cells were located in those parts of the transitional
      zone between fields 17 and 18 whose retinotopic coordinates corresponded to the
      column coordinates (as in intact cats). Other labeled cells were located in
      fields 17 and 18 and were grouped into clusters located at distances of about
      1000 microm from the marginal clusters of the transitional zone. The locations of
      labeled cells in the lateral geniculate body showed that most columns receive
      inputs from the ipsilateral eye. Evidence for eye specificity of these
      monosynaptic interhemisphere connections is presented. The functional
      significance of changes in these connections in bilateral strabismus is
      discussed.

PMID- 17024343
TI  - Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis.
AB  - B and T lymphocyte attenuator (BTLA) is an immuno-inhibitory receptor with the
      ability to deliver inhibitory signal for suppressing lymphocyte activation. To
      test the potential association of the human BTLA gene with the development of
      rheumatoid arthritis (RA), a genetic case-control association study was
      conducted, by using a single nucleotide polymorphism (SNP), C+800T SNP, in the
      exon 5 of the human BTLA gene for genotyping 93 RA patients and 294 normal
      control individuals. The results showed that there is statistically significant
      difference in the genotype distributions between RA and control groups (p =
      0.022). When compared with the heterozygous genotype (C/T genotype), the
      homozygous genotype (C/C or T/T genotype) appears to confer the increased risk of
      the RA susceptibility with the odds ratio of 1.88 (p = 0.015). These data
      indicate the significant association between the C+800T SNP in the BTLA gene with
      the RA susceptibility.

PMID- 17024342
TI  - Objective measurement of human visual acuity by visual evoked potentials.
AB  - Electrophysiological studies were performed to measure the threshold (upper end
      of range) spatial frequency using visual evoked potentials and comparison with
      visual acuity neuron 26 healthy subjects. The aim of the present work was to
      create a method for objective measurement of visual acuity. This was addressed by
      initial measurements using a universally accepted method of visual stimulation
      and processing of electroencephalograms, which allows errors due to individual
      differences in visual system function to be minimized. These experiments yielded
      a strong correlation between the threshold spatial frequency of the test grid
      yielding an evoked potential on presentation and visual acuity, in degrees,
      expressed as the resolving ability of the visual system for this optotype. A
      logarithmic relationship was found between these values and an equation allowing
      automated calculation of visual acuity (resolving ability) from
      electrophysiological data was derived. The results were independent of the
      subject's responses and therefore provides a maximally objective assessment of
      visual acuity.

PMID- 17024345
TI  - Appropriateness of US and international BMI-for-age reference curves in defining
      adiposity among Israeli school children.
AB  - Effective surveillance of trends in paediatric overweight and obesity requires
      the establishment of valid cutoff values to identify children at risk. In Israel,
      standard values for childhood BMI-for-age are currently based on growth charts
      published by the US Centers for Disease Control and Prevention. However, the
      appropriateness of using US reference values in populations outside the US is
      questionable, due to inherent differences in ethnicity, culture and socioeconomic
      status. We recorded data from 9,988 children aged 6-12 selected by random cluster
      sampling within the framework of school-based health surveys conducted in Israel
      during the years 1997 and 2000. We constructed population-specific centile BMI
      for-age curves valid for Israeli children, and compared these curves to current
      standard US and international reference values. Curves were constructed using LMS
      statistical curve smoothing methods. The data set of Israeli schoolchildren
      produced reference centiles substantially different than those based on US
      children. Israeli reference values were closer to centile curves published by the
      International Obesity Task Force. In conclusion, local and national health
      planners should recognize the intrinsic limitations associated with the use of
      "standard" reference values in defining paediatric overweight and obesity in
      dissimilar populations. The results of this large population-based study
      highlight the need for population-specific BMI-for-age reference values, in order
      to accurately describe the prevalence of paediatric overweight and obesity.

PMID- 17024346
TI  - Early diagnosis of iliopsoas pyomyositis by computed tomography and muscle biopsy
      in an epileptic child.

PMID- 17024348
TI  - Growth in treated classical galactosemia patients.
AB  - Decreased height and weight in treated children with classical galactosemia have
      been reported. However, growth has not been extensively studied. Patients might
      be at risk for an abnormal growth because of either disease-related intrinsic
      factors or diet-related factors. The objective was to gain insight in growth in
      treated children and adolescents with classical galactosemia. The studied
      population was a previously reported group of 40 classical galactosemia children.
      Prenatal growth was evaluated using length, weight and head circumference (HC)
      data from welfare centers or parents. Postnatal growth was evaluated using three
      height and weight measurements at baseline, 1 and 2 years to calculate growth
      velocities. Height Z-score was also corrected for target height Z-score (height Z
      score divided by target height Z-score). Linear regression analysis was performed
      between growth velocities, IGF-I, IGFBP-3, dietary intake and galactose-1
      phosphate-uridyltransferase activity. We found normal length (median 50.5 cm),
      weight (median 3,255 grams) and HC (median 33.9 cm) at birth. Mean height growth
      velocity was 0.87+/-1.2 for boys and -0.89+/-2.1 for girls, and mean weight
      growth velocity was 0.91+/-1.6 for boys and -0.74+/-1.3 for girls. Mean height
      corrected for target height was -1.5+/-0.9 in girls and -0.6+/-0.7 in boys.
      Height growth velocity was correlated with IGF-I (Pearson correlation= 0.499),
      IGFBP-3 (Pearson correlation 0.4) and height Z-scores corrected for target height
      Z-scores (Pearson correlation=0.550). Five children grew beyond the age of 18
      years. In conclusion, prenatal growth was normal but postnatal growth was
      affected. Predicted final height is less than target height in most patients;
      however, target height might be reached for the children who grow beyond the age
      of 18. Decreased IGF-I and IGFBP-3 and or suboptimal hormonal replacement in
      girls might play a role.

PMID- 17024347
TI  - Expression of multidrug resistance P-glycoprotein on lymphocytes from nephrotic
      children treated with cyclosporine A and ACE-inhibitor.
AB  - The aim of this work was to determine the expression of P-glycoprotein (P-gp) on
      peripheral lymphocytes (CD3) in children with steroid-dependent nephrotic
      syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment.
      The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a
      subsequent proteinuria relapse at the time of prednisone dose reduction. All
      nephrotic syndrome (NS) children were examined three times: A--at proteinuria
      relapse, before CyA treatment; B--after 3 months; C--after 12 months of CyA
      administration. The control group (II) consisted of 20 healthy children. CD3/P-gp
      was measured using a flow cytometry assay. The serum CyA level was assessed by
      means of the immunofluorescence method. The expression of CD3/P-gp in NS relapse,
      prior to CyA+ACE-I administration, was much higher (median 9.15%, range 1.50
      13.50%) when compared to healthy controls (median 1.20%, range 0.30-5.70%). The
      absolute number of CD3/P-gp in this examination was almost five times higher when
      compared to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy, the
      expression of CD3/P-gp decreased dramatically and was similar to the controls.
      Similar results were obtained after 12 months of treatment. A strong negative
      correlation was found between CD3/P-gp and serum CyA concentration in both
      examinations (r=-0.624, p<0.01; r=-0.464, p<0.01). We conclude that the results
      of our studies indicate that CyA+ACE-I in SDNS inhibits the expression of P-gp.
      CyA is an alternative therapy that may lead to the optimization of glucocorticoid
      (GC) doses, thus, reducing the risk that is associated with the treatment.

PMID- 17024349
TI  - Thirty years of the Union of National European Paediatric Societies and
      Associations (UNEPSA).
AB  - BACKGROUND: The Union of National European Paediatric Societies and Associations
      was founded in 1976 in Rotterdam. Thirty years later, the authors--former
      presidents and secretaries general--present a retrospective on the activities and
      achievements of UNEPSA. In 2006, 36 of 46 (78%) European countries, including
      some countries of the former Soviet Union, were members of UNEPSA. UNEPSA has
      created a forum for the mutual discussion of matters concerning paediatrics.
      UNEPSA is closely linked with the International Pediatric Association (IPA). It
      was never UNEPSA's ambition to promote a uniform European paediatrics. In the 30
      years of its existence, it became clear that the diversity of paediatric care in
      different countries in Europe is extreme. During the "cold war", UNEPSA was able
      to cross boundaries between socialist and capitalist countries in Europe, and it
      was due to the activity of individual members of the UNEPSA council that clinical
      co-operation and research activities were initiated crossing many political
      borders. Annual meetings of national paediatric presidents focus on the most
      urgent problems of paediatric health care. "Europaediatrics" became the tri
      annual congress for all general paediatricians and paediatric sub-specialists in
      Europe. The main research activities of UNEPSA concentrated on identifying the
      demography of primary, secondary and tertiary care paediatrics in Europe.
      CONCLUSION: UNEPSA is an active paediatric association representing more than
      three quarters of all European countries. After 30 years, it is still an
      expanding and vital instrument in improving the medical care of all children and
      the co-operation of their carers in Europe.

PMID- 17024350
TI  - Prevalence of congenital adrenal hyperplasia among sudden infant death in the
      Czech Republic and Austria.
AB  - This study aimed to estimate the number of infants who died of unrecognized
      congenital adrenal hyperplasia (CAH) in Austria and the Czech Republic within the
      past 13 years, before the introduction of adequate neonatal screening. The study
      was based on retrospective analysis of neonatal screening cards of 242 infants
      who died suddenly between 7 days and 12 months of age and whose cause of death
      could not be identified. 17-hydroxyprogesterone (17-OHP) was measured by
      fluoroimmunoassay and positive samples were subsequently genotyped. Three infants
      out of 242 may have had unrecognized CAH due to CYP21 (steroid 21-hydroxylase)
      gene defect. Their newborn 17-OHP levels and CYP21 genotypes were 706 nmol/l and
      del/conv//del/conv, 53 nmol/l and I2//I2, and 811 nmol/l and I2//Gln318stop,
      respectively. CAH due to CYP21 defect can lead to sudden unexpected death without
      prior symptoms typical for the condition. Hence, newborn screening would have
      prevented these deaths had it been available. In addition, we have shown that the
      I2 point mutation that is expected to lead to simple virilizing form may lead to
      a fatal outcome.

PMID- 17024351
TI  - Distribution of Cryptosporidium parvum subtypes in calves in eastern United
      States.
AB  - Cryptosporidium parvum DNA from 175 neonatal calves on 16 farms in eight eastern
      states in the United States was subtyped by sequence analysis of the 60-kDa
      glycoprotein gene to determinate the parasite genetic diversity. Six subtypes of
      the IIa subtype family were found. Subtype IIaA15G2R1, which is the predominant
      C. parvum subtype in calves in many parts of the world, was identified in 77% of
      the C. parvum DNA from calves. Several farms had more than one C. parvum subtype
      and a few calves had infections with mixed subtypes. Distribution of subtypes
      differed geographically. Diversity of C. parvum in calves in eastern United
      States was lower than that previously seen in Michigan and southern Ontario. The
      high prevalence of one subtype in calves worldwide and frequent detection of this
      subtype in humans suggests that parasite fitness probably plays an important role
      in transmission of cryptosporidiosis among cattle and in zoonotic infections.

PMID- 17024352
TI  - Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic
      form Trypanosoma brucei.
AB  - Glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3-
      and 2-phosphoglycerate (3-PG and 2-PG) which is performed by phosphoglycerate
      mutases (PGAMs) which can be cofactor dependant (dPGAM) or cofactor independent
      (iPGAM). The African trypanosome, Trypanosoma brucei, possesses the iPGAM form
      which is thought to play an important role in glycolysis. Here, we report on the
      use of RNA interference to down-regulate the T. brucei iPGAM in procyclic form T.
      brucei and evaluation of the resulting phenotype. We first demonstrated
      biochemically that depletion of the steady state levels of iPGM mRNA correlates
      with a marked reduction of enzyme activity. We further show that iPGAM is
      required for cell growth in procyclic T. brucei.

PMID- 17024353
TI  - Immunological cross-reactivity analysis on recombinant histamine-releasing
      factors from Schistosoma japonicum, Clonorchis sinensis, and Wistar rat.
AB  - Studies have demonstrated a declined incidence of allergic disorders in the
      population with helminthic infection. Though several hypotheses have been
      proposed to explain how helminthic infection protected people against allergies,
      the underlying mechanisms remain poorly understood. A human histamine-releasing
      factor (HRF) has been proved to be closely related to the development of allergic
      disorders and the homologues are ubiquitously expressed in all eukaryotic
      organisms including parasites. To study the role of this HRF in the relationship
      between parasitic infection and allergic diseases with experimental model of
      rats, the cDNA of the homologues of the human HRF from Wistar rat, Schistosoma
      japonicum, and Clonorchis sinensis containing a coding region of 519, 510, and
      510 bp, respectively, were cloned. In addition, the cross-reactivity between
      recombinant rat HRF (rRHRF) and recombinant S. japonicum HRF (rSjHRF) as well as
      that between rRHRF and recombinant C. sinensis HRF (rCsHRF) was identified with
      ELISA and Western blotting. Based on their detected cross-reactivities, a
      hypothesis was put forward that the anti-parasitic HRFs antibodies could inhibit
      the effects of host HRF and those of parasitic HRFs and thus decreased the host
      sensitivities to allergens.

PMID- 17024354
TI  - Effect of oregano (Origanum vulgare L.) and thyme (Thymus vulgaris L.) essential
      oils on Trypanosoma cruzi (Protozoa: Kinetoplastida) growth and ultrastructure.
AB  - In the present work, we have investigated the effect of essential oils obtained
      from Origanum vulgare L. (oregano) and Thymus vulgaris L. (thyme) on growth and
      ultrastructure of diverse evolutive forms of Trypanosoma cruzi. Culture
      epimastigotes and bloodstream trypomastigotes were incubated for 24 h with
      different concentrations of oregano or thyme essential oils and with thymol (the
      main constituent of thyme), and the inhibitory concentration (IC)(50) was
      determined by cell counting. Crude extract of oregano essential oil inhibited
      epimastigote growth (IC(50)/24 h = 175 microg/ml) and also induced trypomastigote
      lysis (IC(50)/24 h = 115 microg/ml). Thyme essential oil presented IC(50)/24 h
      values of 77 microg/ml for epimastigotes and 38 mug/ml for trypomastigotes, while
      treatment with thymol resulted in an IC(50)/24 h of 62 microg/ml for
      epimastigotes and 53 microg/ml for trypomastigotes. Scanning electron microscopy
      of treated cells showed few morphological alterations at the plasma membrane.
      Observation by transmission electron microscopy showed cytoplasmic swelling with
      occasional morphological alterations in plasma and flagellar membrane. Our data
      indicate that oregano and thyme essential oils are effective against T. cruzi,
      with higher activity of thyme, and that thymol may be the main component
      responsible for the trypanocidal activity.

PMID- 17024355
TI  - First report of Neospora caninum-associated bovine abortion in Mashhad area,
      Iran.
AB  - Neospora caninum is an apicomplexan protozoan which causes abortion in cattle
      worldwide. The present study was designed to assess the importance of bovine
      neosporosis for causing abortion in Iranian cattle. Infection was primarily
      diagnosed by polymerase chain reaction (PCR), complemented with histopathology
      and immunohistochemistry (IHC). One hundred brains of aborted bovine fetuses were
      collected from Iranian dairy herd between 2003 and 2005 in Mashhad area. N.
      caninum was detected by PCR in the brains of 13 aborted fetuses. Lesions
      consistent with N. caninum infection were observed in 12 of fetal brains.
      Immunohistochemical examination of brain detected N. caninum organisms in three
      aborted fetuses, and a thick-walled (2 mum) cyst with 50 mum diameter was
      identified in one of the IHC-positive brain. The results indicated that
      neosporosis is an important cause of abortion in dairy cattle of Iran.

PMID- 17024356
TI  - Effect of a cysteine protease inhibitor on Fasciola hepatica (liver fluke)
      fecundity, egg viability, parasite burden, and size in experimentally infected
      sheep.
AB  - Fasciola hepatica secretes proteolytic enzymes during liver invasion. The present
      study examined the effects of the cysteine protease inhibitor Ep-475 on sheep
      considering the following variables: serum levels of aspartate aminotransferase,
      L-lactate dehydrogenase, and gamma-glutamyltransferase, liver fluke fecundity,
      egg viability, parasite burden, and size. Twenty-four male sheep were randomly
      allocated in four groups of six animals each as follows: group A was infected
      with F. hepatica metacercariae and treated with 50 mg/kg of Ep-475, group B was
      infected and untreated, group C was uninfected and treated, and group D was
      uninfected and untreated. All animals were euthanized 10 weeks after the
      experimental infection. Serum activities of enzymes in infected animals were
      significantly lower in Ep-475-treated sheep than in untreated controls, although
      liver damage was produced. No significant reduction in total worm burden was
      observed between treated and untreated sheep. However, there was a significant
      difference on the average size, structure development, ova counts, and egg
      viability of liver flukes from these two groups. Results showed that Ep-475
      reduces liver damage due to fasciolosis and induces an impairment of liver fluke
      growth and fecundity. These effects pinpoint liver fluke proteases as potential
      targets for pharmacological intervention.

PMID- 17024358
TI  - Purification and biochemical characterization of cytosolic glutathione-S
      transferase from malarial parasites Plasmodium yoelii.
AB  - Glutathione (GSH) metabolism represents a potential target for antiparasitic drug
      design. Glutathione-S-transferase (GST), an important enzyme of the GSH cycle, is
      considered to be an essential detoxification enzyme in parasitic species. Soluble
      GST from rodent malarial parasites Plasmodium yoelii was purified to homogeneity
      using a combination of salt precipitation, affinity chromatography on GSH
      sepharose 6B and ultrafiltration. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis revealed a single band and activity staining
      was also detected on PAGE gels. Kinetic studies on the purified enzyme revealed
      significant differences between the parasitic and mammalian enzymes. The purified
      enzyme exhibited an optimum pH of 8.2 and K (m) values of 0.2+/-0.213 and 3.3+/
      0.056 mM with respect to co-substrate GSH and substrate 1-chloro-2, 4
      dinitrobenzene (CDNB), respectively. Hemin, the known mammalian GST inhibitor was
      found to be a potent inhibitor of P. yoelii GST, with a K (i) of 4.0 microM.

PMID- 17024357
TI  - Subversion of innate and adaptive immune responses by Toxoplasma gondii.
AB  - The intracellular apicomplexan parasite Toxoplasma gondii is able to survive and
      persist in immunocompetent intermediate hosts for the host's life span. This is
      despite the induction of a vigorous humoral and -- more importantly -- cell
      mediated immune response during infection. In order to establish and maintain
      such chronic infections, however, T. gondii has evolved multiple strategies to
      avoid or to interfere with potentially efficient anti-parasitic immune responses
      of the host. Such immune evasion includes (1) indirect mechanisms by altering the
      expression and secretion of immunomodulatory cytokines or by altering the
      viability of immune cells and (2) direct mechanisms by establishing a lifestyle
      within a suitable intracellular niche and by interference with intracellular
      signaling cascades, thereby abolishing a number of antimicrobial effector
      mechanisms of the host. Despite the parasite's ability to interfere successfully
      with the host's efforts to eradicate the infection, the immune response is,
      however, not completely abrogated but is rather partially diminished after
      infection. T. gondii thus keeps a delicate balance between induction and
      suppression of the host's immune response in order to guarantee the survival of
      the host as a safe harbor for parasite development and to allow its transmission
      to the definitive host.

PMID- 17024359
TI  - Genotypes and in vivo resistance of Plasmodium falciparum isolates in an endemic
      region of Iran.
AB  - Mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase
      (DHPS) genes of Plasmodium falciparum have been correlated with and used to
      detect antifolate treatment failure, such as sulfadoxine-pyrimethamine (SP), in
      regions endemic for malaria. To determine the association between molecular
      markers of SP resistance and in vivo drug resistance, a quick and simple
      technique that detects single nucleotide polymorphisms in the DHFR and DHPS
      genes, using PCR-ELISA and sequence-specific oligonucleotide probes, was applied
      to 53 isolates obtained from an in vivo study in Sistan and Baluchistan Province,
      in southeastern Iran. Overall, 11.3% of these isolates were obtained from
      patients with SP treatment failure. Four DHFR polymorphisms (codons 51, 59, 108,
      and 164) and five DHPS polymorphisms (codons 436, 437, 540, 581, and 613) were
      investigated. Mutations DHFR Asn-108, DHFR Arg-59, and DHPS 436-Ala/Phe were very
      common (100, 81.1, and 85%, respectively). Plasmodium falciparum was isolated
      from 96% of patients with at least two DHFR/DHPS mutations. All resistant
      isolates had at least three mutations. The high prevalence of mutation associated
      with antifolate resistance may point toward low drug efficacy in the future.

PMID- 17024360
TI  - The first detection of Neospora caninum DNA in the colostrum of infected cows.
AB  - Limited data is available on the vertical transmission of Neospora caninum via
      the colostrum. The results of our previous research revealed the presence of N.
      caninum DNA in the milk of seropositive cows. The aim of the present work is to
      demonstrate parasite DNA in colostrum samples. A polymerase chain reaction using
      Np21 and Np6 primers was applied to DNA isolated from the colostrum sediment in
      order to amplify the corresponding genomic Nc-5 region. The expected 328-bp
      product was obtained in colostrum samples collected both on the calving day and
      the day after. This is the first detection of N. caninum DNA in the colostrum of
      seropositive cows, and these findings implicate the possibility of N. caninum
      transmission through the colostrum.

PMID- 17024361
TI  - Evaluation of effects of albendazole on the kinetics of cytosolic glutathione
      transferase in skeletal muscles during experimental trichinellosis in mice.
AB  - In this study, the effect of trichinellosis as well as the effect of albendazole
      treatment on the kinetics of substrate saturation of cytosolic glutathione
      transferase (GST) in the skeletal muscles from infected mice was examined because
      the idea of multifunctional mode of action of anthelmintic drugs was considered.
      Our results pointed out to the influence of trichinellosis and albendazole
      treatment on the quaternary structure of GST in mouse muscles. A double
      reciprocal plot of GST saturation in control mice was biphasic with apparent low
      and high K (m) values equal to 0.54 and 1.0 mM, respectively. Infection with
      Trichinella spiralis in the third week postinfection caused a 2.3-fold increase
      in the high K (m) value and at the same time a 2.8-fold decrease in the low K
      (m). In the sixth week postinfection, the high K (m) value was unchanged, but the
      low K (m) value increased 2.3 times. Calculated from the double reciprocal plot
      of GST substrate saturation in muscles from infected and treated mice (measured
      in the third week postinfection only), the high K (m) value increased 1.4 times
      relative to the respective controls. The normal substrate saturation plot of GST
      in treated mice has a clearly "double sigmoid" character. Our results suggest
      that despite the complicated character of the GST saturation curve, albendazole
      seems to act as an allosteric activator for cytosolic GST in infected mouse
      muscles.

PMID- 17024362
TI  - Antiplasmodial activity of triterpenoid isolated from whole plants of Viola genus
      from South Korea.
AB  - Species of the Viola genus, used in traditional medicines for the treatment of
      parasites, were collected and petroleum ether extract was obtained by sonication.
      The antiplasmodial activity of petroleum ether extracts was evaluated in vitro
      against the chloroquine-resistant FcB1 strain of Plasmodium falciparum.
      Bioactivity-guided fractionation of the petroleum ether extracts of the whole
      plants of Viola verecunda has led to the isolation of epi-oleanolic acid, a
      triterpenoid, displaying high antiplasmodial activity (IC(50) 0.18 mug/ml). This
      is the first report of the isolation and antiplasmodial activity of epi-oleanolic
      acid from this species.

PMID- 17024363
TI  - Viability staining and animal infectivity of Cryptosporidium andersoni oocysts
      after long-term storage.
AB  - Preservation of biological properties of oocysts during the storage is critical
      for experimental work. Stomach species of cryptosporidia are less resistant
      against external influences, and their infectivity decreases rapidly in
      comparison with intestinal cryptosporidia. Cryptosporidium andersoni oocysts lost
      their infectivity for gerbil (Meriones unguiculatus) after 7 months storage in
      deionised water (DW) or in 2.5% potassium dichromate solution (PDS). Evaluation
      of oocyst viability by flow cytometry indicates higher percentage of viable
      oocysts stored in PDS than in DW, particularly after 6 months of storage.
      However, direct counting using fluorescent microscope revealed that these results
      are false and are influenced by the change of staining properties during the
      storage in PDS. Moreover, the examination of oocyst integrity by flow cytometry
      revealed that oocysts preserved in PDS kept their wall integrity longer than
      those stored in DW, and this fact should be taken into consideration during
      quantification of oocyst survival.

PMID- 17024364
TI  - Fibrillin I gene polymorphism is associated with tall stature of normal
      individuals.
AB  - In order to test the hypothesis that polymorphisms of the Marfan syndrome gene
      (FBN1) might affect the stature (height) of normal individuals, we genotyped
      three exonic SNPs on 428 males, 219 with tall stature (>2 SD) and 209 with normal
      stature (within +/-1 SD). One of the SNPs, rs8033037, in exon 15 showed a
      significant correlation (P = 0.0061) with the adult height, suggesting that FBN1
      is one of the 'stature genes' of normal individuals.

PMID- 17024365
TI  - Genetics of preeclampsia: paradigm shifts.
AB  - Segregation of preeclampsia into early-onset, placental and late-onset, maternal
      subtypes along with the acknowledgement of the contribution of epigenetics in
      placentally expressed genes proved to be a key first step in the identification
      of essential gene variants associated with preeclampsia. Application of this
      insight to other populations and related pregnancy-induced syndromes, such as
      HELLP, and acknowledgment of the features shared between chromosomal loci
      associated with preeclampsia in different populations provide the rationale for
      new strategies for the identification of susceptibility genes and for new and
      more effective diagnostic strategies.

PMID- 17024366
TI  - Lack of association between rs7566605 and obesity in a Chinese population.

PMID- 17024367
TI  - Significant linkage to airway responsiveness on chromosome 12q24 in families of
      children with asthma in Costa Rica.
AB  - Although asthma is a major public health problem in certain Hispanic subgroups in
      the United States and Latin America, only one genome scan for asthma has included
      Hispanic individuals. Because of small sample size, that study had limited
      statistical power to detect linkage to asthma and its intermediate phenotypes in
      Hispanic participants. To identify genomic regions that contain susceptibility
      genes for asthma and airway responsiveness in an isolated Hispanic population
      living in the Central Valley of Costa Rica, we conducted a genome-wide linkage
      analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of
      eight large pedigrees of Costa Rican children with asthma. Nonparametric
      multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele
      sharing statistic, and variance component models were used for the multipoint
      linkage analysis of airway responsiveness as a quantitative phenotype. All
      linkage analyses were repeated after exclusion of the phenotypic data of former
      and current smokers. Chromosome 12q showed some evidence of linkage to asthma,
      particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive
      evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33
      at 146 cM). After genotyping 18 additional short-tandem repeat markers on
      chromosome 12q, there was significant evidence of linkage to airway
      responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively
      narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM).
      Our results suggest that chromosome 12q24.31 contains a locus (or loci) that
      influence a critical intermediate phenotype of asthma (airway responsiveness) in
      Costa Ricans.

PMID- 17024368
TI  - High-resolution mapping of DNA methylation in human genome using oligonucleotide
      tiling array.
AB  - DNA methylation is an epigenetic mark crucial in regulation of gene expression.
      Aberrant DNA methylation causes silencing of tumor suppressor genes and promotes
      chromosomal instability in human cancers. Most of previous studies for DNA
      methylation have focused on limited genomic regions, such as selected genes or
      promoter CpG islands (CGIs) containing recognition sites of methylation-sensitive
      restriction enzymes. Here, we describe a method for high-resolution analysis of
      DNA methylation using oligonucleotide tiling arrays. The input material is
      methylated DNA immunoprecipitated with anti-methylcytosine antibodies. We
      examined the ENCODE region ( approximately 1% of human genome) in three human
      colorectal cancer cell lines and identified over 700 candidate methylated sites
      (CMS), where 24 of 25 CMS selected randomly were subsequently verified by
      bisulfite sequencing. CMS were enriched in the 5' regulatory regions and the 3'
      regions of genes. We also compared DNA methylation patterns with histone H3 and
      H4 acetylation patterns in the HOXA cluster region. Our analysis revealed no
      acetylated histones in the hypermethylated region, demonstrating reciprocal
      relationship between DNA methylation and histone H3 and H4 acetylation. Our
      method recognizes DNA methylation with little bias by genomic location and,
      therefore, is useful for comprehensive high-resolution analysis of DNA
      methylation providing new findings in the epigenomics.

PMID- 17024369
TI  - Association of Hck genetic polymorphisms with gene expression and COPD.
AB  - Polymorphonuclear leukocytes (PMNs) are major effector cells in the chronic
      airway inflammation in chronic obstructive pulmonary disease (COPD). PMN
      degranulation is associated with degradation of extracellular matrix and tissue
      damage. Hck is an essential molecule in the signaling pathway regulating PMN
      degranulation. We hypothesized that polymorphisms affect the expression level of
      Hck, which, in turn, modulates PMN mediator release and tissue damage and
      influences the development of COPD. Here we systematically investigated genetic
      tag polymorphisms of the Hck gene, Hck mRNA and protein expression pattern in
      PMNs, and PMN mediator release (myeloperoxidase) in 60 healthy white subjects,
      and assessed their association with the use of several genetic models. The
      association of genetic polymorphisms with COPD-related phenotypes was determined
      in the lung healthy study cohort (LHS). We identified a novel 15 bp
      insertion/deletion polymorphism (8,656 L/S) in intron 1 of the Hck gene, which
      was associated with differential expression of Hck protein and PMN
      myeloperoxidase release. In the LHS cohort, there was significant interaction
      between the 8,656 L/S polymorphism and smoking on baseline lung function and
      8,656 L/S was associated with bronchodilator response. These data suggest that
      the insertion/deletion polymorphism could be a functional polymorphism of the Hck
      gene, may contribute to COPD pathogenesis and modify COPD-related phenotypes.

PMID- 17024370
TI  - Predictors of uptake of obesity genetic testing among affected adults.
AB  - Given that a large number of candidate genes coding for a tendency toward obesity
      have been identified and some findings have been replicated, we explored
      characteristics of those who would be most likely to obtain future genetic
      testing for this tendency. During a series of focus groups, obese respondents
      rated their likelihood of obtaining testing under conditions in which either
      genetically-targeted drug treatment would be available, a positive test would be
      associated with a prognosis for developing diabetes, or neither of these.
      Interest in testing was greater given the first two scenarios than the third.
      Older age and belief that genetics were an important cause of obesity were
      associated with greater interest. For the first two scenarios, higher educational
      status was associated with greater interest, while for the third, respondents who
      said emotional issues caused overweight and those who crash-dieted intermittently
      were more likely to want genetic testing. Although further research is required
      to validate these findings, this study is the first published report of
      respondents' ratings of likelihood to obtain genetic testing for propensity to
      obesity, and suggests strong interest in genetic testing among some people, even
      in the absence of further treatment implications of the test.

PMID- 17024371
TI  - The GAA triplet-repeat is unstable in the context of the human FXN locus and
      displays age-dependent expansions in cerebellum and DRG in a transgenic mouse
      model.
AB  - Friedreich ataxia (FRDA) is caused by homozygosity for FXN alleles containing an
      expanded GAA triplet-repeat (GAA-TR) sequence. Patients have progressive
      neurodegeneration of the dorsal root ganglia (DRG) and in later stages the
      cerebellum may be involved. The expanded GAA-TR sequence is unstable in somatic
      cells in vivo, and although the mechanism of instability remains unknown, we
      hypothesized that age-dependent and tissue-specific somatic instability may be a
      determinant of the progressive pathology involving DRG and cerebellum. We show
      that transgenic mice containing the expanded GAA-TR sequence (190 or 82 triplets)
      in the context of the human FXN locus show tissue-specific and age-dependent
      somatic instability that is compatible with this hypothesis. Small pool PCR
      analysis, which allows quantitative analysis of repeat instability by assaying
      individual transgenes in vivo, showed age-dependent expansions specifically in
      the cerebellum and DRG. The (GAA)(190) allele showed some instability by 2
      months, progressed at about 0.3-0.4 triplets per week, resulting in a significant
      number of expansions by 12 months. Repeat length was found to determine the age
      of onset of somatic instability, and the rate and magnitude of mutation. Given
      the low level of cerebellar instability seen by others in multiple transgenic
      mice with expanded CAG/CTG repeats, our data indicate that somatic instability of
      the GAA-TR sequence is likely mediated by unique tissue-specific factors. This
      mouse model will serve as a useful tool to delineate the mechanism(s) of disease
      specific somatic instability in FRDA.

PMID- 17024373
TI  - A nonsense mutation-created intraexonic splice site is active in the lymphocytes,
      but not in the skeletal muscle of a DMD patient.
AB  - Production of semi-functional dystrophin mRNA from the dystrophin gene encoding a
      premature stop codon has been shown to modify the severe phenotype of Duchenne
      muscular dystrophy (DMD). In this study, we report the tissue-specific production
      of semi-functional dystrophin mRNA via activation of a nonsense mutation-created
      intraexonic splice acceptor site. In a DMD patient a novel nonsense mutation was
      identified in exon 42. In his lymphocytes semi-functional dystrophin mRNA with a
      63-nucleotide deletion in exon 42 (dys-63) was found to be produced. In vitro
      splicing assay using hybrid minigenes disclosed that the mutation-created
      intraexonic splice acceptor site was activated. In his skeletal muscle cells,
      however, only the authentically spliced dystrophin mRNA was found. This finding
      identifies the modulation of the splicing of muscle dystrophin mRNA in cases of
      DMD as a potential target for therapeutic strategies to generate a milder
      phenotype for this disease.

PMID- 17024372
TI  - A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3.
AB  - Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically
      diverse forms of defective tooth enamel development. AI has been reported to
      exhibit a variety of inheritance patterns, and several loci have been identified
      that are associated with AI. We have performed a genome-wide scan in a large
      Brazilian family segregating an autosomal dominant form of AI and mapped a novel
      locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker
      D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region
      according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at
      143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were
      identified based on gene ontology and microarray-facilitated gene selection using
      the expression of murine orthologues in dental tissue, and examined for the
      presence of a mutation. However, no causative mutation was identified.

PMID- 17024374
TI  - Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld
      syndrome patients.
AB  - Ellis-van Creveld syndrome (EvC) is caused by mutations in EVC and EVC2, genes in
      a divergent orientation separated by only 2.6 kb. We systematically sought
      mutations in both genes in a panel of 65 affected individuals to assess the
      proportion of cases resulting from mutations in each gene. We PCR amplified and
      sequenced the coding exons of both genes. We investigated mutations that could
      affect splicing by in vitro splicing assays and cDNA analysis. We have identified
      EVC mutations in 20 cases (31%); in all of these we have detected the mutation on
      each allele. We have identified EVC2 mutations in 25 cases (38%); in 22 of these
      we have isolated a mutation on each allele. The majority of the mutations
      introduce a premature termination codon. We sequenced the region between the two
      genes in 10 of the 20 cases in which we had not identified a mutation in either
      gene, revealing only one SNP that was not a common polymorphism. As we have not
      identified mutations in either gene in 20 cases (31%) it is possible that there
      is further genetic heterogeneity.

PMID- 17024376
TI  - Can parasites be indicators of free-living diversity? Relationships between
      species richness and the abundance of larval trematodes and of local benthos and
      fishes.
AB  - Measuring biodiversity is difficult. This has led to efforts to seek taxa whose
      species richness correlates with the species richness of other taxa. Such
      indicator taxa could then reduce the time and cost of assessing the biodiversity
      of the more extensive community. The search for species richness correlations has
      yielded mixed results, however. This may be primarily because of the lack of
      functional relationships between the taxa studied. Trematode parasites are highly
      promising bioindicators. Diverse assemblages of larval trematode parasites are
      easily sampled in intermediate host snails. Through their life cycles these
      parasites are functionally coupled with the surrounding free-living diversity of
      vertebrate and invertebrate animals. It has been shown that larval trematodes in
      snails correlate positively with bird diversity and abundance. Here, we explore
      whether trematodes also correlate with standard measures of fishes, and large and
      small benthos, for 32 sites in three wetlands. We found associations between
      trematodes and benthic communities that were not consistent across wetlands. The
      associations were, however, consistently positive for large benthic species
      richness and density. Some of the contrasting associations between trematode and
      benthos may be explained by negative associations between large and small
      benthos. We found no associations with fish communities (probably because of the
      inadequacy of standard "snapshot" sampling methods for highly mobile fishes). The
      results support further exploration of trematodes as bioindicators of diversity
      and abundance of animal communities.

PMID- 17024375
TI  - Family-based association study of matrix metalloproteinase-3 and -9 haplotypes
      with susceptibility to ischemic white matter injury.
AB  - Susceptibility to ischemic damage to the subcortical white matter of the brain
      has a strong genetic basis. Dysregulation of matrix metalloproteinases (MMPs)
      contributes to loss of cerebrovascular integrity and white matter injury. We
      investigated whether sequence variation in the genes encoding MMP3 and MMP9 is
      associated with variation in leukoaraiosis volume, determined by magnetic
      resonance imaging, in non-Hispanic whites and African-Americans using family
      based association tests. Seven hundred and fifty-six white and 671 African
      American individuals from sibships ascertained through two or more siblings with
      hypertension were genotyped for 7 and 8 haplotype-tagging polymorphisms in the
      MMP3 and MMP9 genes, respectively. MMP3 sequence variation was significantly
      associated with variation in leukoaraiosis volume in Whites. Two common
      haplotypes with opposing relationships to leukoaraiosis volume were identified.
      MMP9 sequence variation was also significantly associated with variation in
      leukoaraiosis volume in both African-Americans and Whites. Different haplotypes
      contributed to these associations in the two racial groups. These findings add to
      the growing body of evidence from animal models and human clinical studies
      suggesting a role of MMPs in ischemic white matter injury. They provide the basis
      for further investigation of the role of these genes in susceptibility and/or
      progression to clinical disease.

PMID- 17024378
TI  - Rainfall and labile carbon availability control litter nitrogen dynamics in a
      tropical dry forest.
AB  - N cycling in tropical dry forests is driven by rainfall seasonality but the
      mechanisms involved are not well understood. We studied the seasonal variation in
      N dynamics and microbial biomass in the surface litter of a tropical dry forest
      ecosystem in Mexico over a 2-year period. Litter was collected at 4 different
      times of the year to determine changes in total, soluble, and microbial C and N
      concentrations. Additionally, litter from each sampling date was incubated under
      laboratory conditions to determine potential C mineralization rate, net N
      mineralization, net C and N microbial immobilization, and net nitrification.
      Litter C concentrations were highest in the early-dry season and lowest in the
      rainy season, while the seasonal changes in N concentrations varied between
      years. Litter P was higher in the rainy than in the early-dry season. Water
      soluble organic C (WSOC) and water-soluble N concentrations were highest during
      the early- and late-dry seasons and represented up to 4.1 and 5.9% of the total C
      and N, respectively. NH (4) (+) and NO (3) (-) showed different seasonal and
      annual variations. They represented an average 23% of soluble N. Microbial C was
      generally higher in the dry than in the wet seasons, while microbial N was lowest
      in the late-dry and highest in the early-rainy seasons. Incubations showed that
      lowest potential C mineralization rates and C and N microbial immobilization
      occurred in rainy season litter, and were positively correlated to WSOC. Net
      nitrification was highest in rainy season litter. Our results showed that the
      seasonal pattern in N dynamics was influenced by rainfall seasonality and labile
      C availability, and not by microbial biomass. We propose a conceptual model to
      hypothesize how N dynamics in the litter layer of the Chamela tropical dry forest
      respond to the seasonal variation in rainfall.

PMID- 17024377
TI  - Soil calcium and plant disease in serpentine ecosystems: a test of the pathogen
      refuge hypothesis.
AB  - Ecologists have long sought mechanistic explanations for the patterns of plant
      distribution and endemism associated with serpentine soils. We conducted the
      first empirical test of the serpentine pathogen refuge hypothesis, which posits
      that the low levels of calcium found in serpentine soils provide associated
      plants with a refuge from attack by pathogens. We measured the range of soil
      calcium concentrations experienced by 16 wild population of California dwarf flax
      (Hesperolinon californicum) and experimentally recreated part of this range in
      the greenhouse by soaking serpentine soils in calcium chloride solutions of
      varying molarity. When flax plants grown in these soils were inoculated with
      spores of the rust fungus Melampsora lini we found a significant negative
      relationship between infection rates and soil calcium concentrations. This result
      refutes the pathogen refuge hypothesis and suggests that serpentine plants, by
      virtue of their association with low calcium soils, may be highly vulnerable to
      attack by pathogens. This interaction between plant nutrition and disease may in
      part explain demographic patterns associated with serpentine plant populations
      and suggests scenarios for the evolution of life history traits and the
      distribution of genetic resistance to infection in serpentine plant communities.

PMID- 17024379
TI  - Salinity and light interactively affect neotropical mangrove seedlings at the
      leaf and whole plant levels.
AB  - We have studied the interactive effects of salinity and light on Avicennia
      germinans mangrove seedlings in greenhouse and field experiments. We hypothesized
      that net photosynthesis, growth, and survivorship rates should increase more with
      an increase in light availability for plants growing at low salinity than for
      those growing at high salinity. This hypothesis was supported by our results for
      net photosynthesis and growth. Net daily photosynthesis did increase more with
      increasing light for low-salinity plants than for high-salinity plants. Stomatal
      conductance, leaf-level transpiration, and internal CO(2) concentrations were
      lower at high than at low salinity. At high light, the ratio of leaf respiration
      to assimilation was 2.5 times greater at high than at low salinity. Stomatal
      limitations and increased respiratory costs may explain why, at high salinity,
      seedlings did not respond to increased light availability with increased net
      photosynthesis. Seedling mass and growth rates increased more with increasing
      light availability at low than at high salinity. Ratios of root mass to leaf mass
      were higher at high salinity, suggesting that either water or nutrient
      limitations may have limited seedling growth at high salinity in response to
      increasing light. The interactive effects of salinity and light on seedling size
      and growth rates observed in the greenhouse were robust in the field, despite the
      presence of other factors in the field--such as inundation, nutrient gradients,
      and herbivory. In the field, seedling survivorship was higher at low than at high
      salinity and increased with light availability. Interestingly, the positive
      effect of light on seedling survivorship was stronger at high salinity,
      indicating that growth and survivorship rates are decoupled. In general, this
      study demonstrates that environmental effects at the leaf-level also influence
      whole plant growth in mangroves.

PMID- 17024380
TI  - Amensalism via webs causes unidirectional shifts of dominance in spider mite
      communities.
AB  - Competitive displacement is considered the most severe consequence of
      interspecific competition; if a superior competitor invades the habitat of an
      inferior species, the inferior species will be displaced. Most displacements
      previously reported among arthropods were caused by exotic species. The lack of
      investigation of displacement among native species may be due to their apparently
      harmonious coexistence, even if it is equivalent to an outcome of interspecific
      association. A seasonal change in the species composition of spider mites, from
      Panonychus ulmi to Tetranychus urticae, is observed in apple trees worldwide.
      Previous laboratory experiments have revealed amensal effects of T. urticae on P.
      ulmi via their webs. Using manipulation experiments in an orchard, we tested
      whether this seasonal change in species composition occurred as the result of
      interspecific competition between these spider mites. Invasion by T. urticae
      prevented an increase in P. ulmi densities throughout the experimental periods.
      Degree of overlap relative to the independent distribution on a leaf-surface
      basis (omega (S)) changed from positive to negative with increasing density of T.
      urticae. T. urticae invasion drove P. ulmi toward upper leaf surfaces (competitor
      free space). The niche adjustment by P. ulmi occurred between leaf surfaces but
      not among leaves. Our findings show that asymmetrical competition between T.
      urticae and P. ulmi plays an important role in this unidirectional displacement
      and that the existence of refuges within a leaf produces the apparently
      harmonious coexistence of the mites and obscures their negative association.

PMID- 17024381
TI  - Linking global warming to amphibian declines through its effects on female body
      condition and survivorship.
AB  - There is general consensus that climate change has contributed to the observed
      decline, and extinction, of many amphibian species throughout the world. However,
      the mechanisms of its effects remain unclear. A laboratory study in 1980-1981 in
      which temperate zone amphibians that were prevented from hibernating had
      decreased growth rates, matured at a smaller size and had increased mortality
      compared with those that hibernated suggested one possible mechanism. I used data
      from a field study of common toads (Bufo bufo) in the UK, between 1983 and 2005,
      to determine whether this also occurs in the field. The results demonstrated two
      pathways by which global warming may cause amphibian declines. First, there was a
      clear relationship between a decline in the body condition of female common toads
      and the occurrence of warmer than average years since 1983. This was paralleled
      by a decline in their annual survival rates with the relationship between these
      two declines being highly correlated. Second, there was a significant
      relationship between the occurrence of mild winters and a reduction in female
      body size, resulting in fewer eggs being laid annually. Climate warming can,
      therefore, act on wild temperate zone amphibians by deleteriously affecting their
      physiology, during and after hibernation, causing increased female mortality
      rates and decreased fecundity in survivors.

PMID- 17024382
TI  - Freezing tolerance in grasses along an altitudinal gradient in the Venezuelan
      Andes.
AB  - The tropical high Andes experience greater daily temperature oscillations
      compared to seasonal ones as well as a high frequency of night frost occurrence
      year round. Survival of organisms, under such environmental conditions, has been
      determined by selective forces which have evolved into adaptations including
      avoidance or tolerance to freezing. These adaptations have been studied in
      different species of trees, shrubs and perennial herbs in paramo ecosystems,
      while they have not been considered in grasses, an important family of the
      paramo. In order to understand survival of Poaceae, resistance mechanisms were
      determined. The study was performed along an altitudinal gradient (2,500-4,200 m
      a.s.l.) in the paramo. Supercooling capacity and frost injury temperature were
      determined in nine species in order to establish cold resistance mechanisms.
      Grasses registered a very low supercooling capacity along the altitudinal
      gradient, with ice formation between -6 and -3 degrees C. On the other hand,
      frost injury temperature oscillated between -18 and -7 degrees C. Our results
      suggest that grasses exhibit freezing tolerance as their main cold resistance
      mechanism. Since grasses grow at ground level, where greatest heat loss takes
      place, tolerance may be related to this life form as reported for other small
      life forms.

PMID- 17024383
TI  - Contrasting effects of rabbit exclusion on nutrient availability and primary
      production in grasslands at different time scales.
AB  - Herbivores influence nutrient cycling and primary production in terrestrial plant
      communities. However, both empirical and theoretical studies have indicated that
      the mechanisms by which herbivores influence nutrient availability, and thus
      their net effects on primary production, might differ between time scales. For a
      grassland in southeast England, we show that the effects of rabbits on primary
      production change over time in a set of grazed plots paired with exclosures
      ranging from 0 to 14 years in age. Herbivore exclusion decreased net aboveground
      primary production (APP) in the short term, but increased APP in the long term.
      APP was closely correlated with N mineralization rates in both grazed and
      ungrazed treatments, and accumulation of litter within the grazing exclosures led
      to higher N mineralization rates in exclosures in the long run. Rabbit grazing
      did not influence litter quality. The low contrast in palatability between
      species and the presence of grazing-tolerant plants might prevent rabbits from
      favoring unpalatable plant species that decompose slowly, in contrast to results
      from other ecosystems. Our results indicate that it is essential to understand
      the effects on N cycling in order to predict the effect of rabbit grazing on APP.
      Rabbits might decrease N mineralization and APP in the long term by increasing
      losses of N from grasslands.

PMID- 17024384
TI  - Water temperature and mixing depth affect timing and magnitude of events during
      spring succession of the plankton.
AB  - In many lakes, the most conspicuous seasonal events are the phytoplankton spring
      bloom and the subsequent clear-water phase, a period of low-phytoplankton biomass
      that is frequently caused by mesozooplankton (Daphnia) grazing. In Central
      European lakes, the timing of the clear-water phase is linked to large-scale
      climatic forcing, with warmer winters being followed by an earlier onset of the
      clear-water phase. Mild winters may favour an early build-up of Daphnia
      populations, both directly through increased surface temperatures and indirectly
      by reducing light limitation and enhancing algal production, all being a
      consequence of earlier thermal stratification. We conducted a field experiment to
      disentangle the separate impacts of stratification depth (affecting light supply)
      and temperature on the magnitude and timing of successional events in the
      plankton. We followed the dynamics of the phytoplankton spring bloom, the clear
      water phase and the spring peak in Daphnia abundance in response to our
      experimental manipulations. Deeper mixing delayed the timing of all spring
      seasonal events and reduced the magnitudes of the phytoplankton bloom and the
      subsequent Daphnia peak. Colder temperatures retarded the timing of the clear
      water phase and the subsequent Daphnia peak, whereas the timing of the
      phytoplankton peak was unrelated to temperature. Most effects of mixing depth
      (light) and temperature manipulations were independent, effects of mixing depth
      being more prevalent than effects of temperature. Because mixing depth governs
      both the light climate and the temperature regime in the mixed surface layer, we
      propose that climate-driven changes in the timing and depth of water column
      stratification may have far-reaching consequences for plankton dynamics and
      should receive increased attention.

PMID- 17024385
TI  - Can overwintering versus diapausing strategy in Daphnia determine match-mismatch
      events in zooplankton-algae interactions?
AB  - Mismatches between predator and prey due to climate change have now been
      documented for a number of systems. Ultimately, a mismatch may have far-reaching
      consequences for ecosystem functioning as decoupling of trophic relationships
      results in trophic cascades. Here, we examine the potential for climate change
      induced mismatches between zooplankton and algae during spring succession, with a
      focus on Daphnia and its algal food. Whereas the development of an overwintering
      population of daphnids may parallel shifts in phytoplankton phenology due to
      climate warming, changes in the photoperiod-temperature interaction may cause the
      emerging population of daphnids to hatch too late and mismatch their
      phytoplankton prey. A decoupling of the trophic relationship between the keystone
      herbivore Daphnia and its algal prey can result in the absence of a spring clear
      water phase. We extended an existing minimal model of seasonal dynamics of
      Daphnia and algae and varied the way the Daphnia population is started in spring,
      i.e., from free swimming individuals or from hatching resting eggs. Our model
      results show that temperature affects the timing of peak abundance in Daphnia and
      algae, and subsequently the timing of the clear water phase. When a population is
      started from a small inoculum of hatching resting eggs, extreme climate warming
      (+6 degrees C) results in a decoupling of trophic relationships and the clear
      water phase fails to occur. In the other scenarios, the trophic relationships
      between Daphnia and its algal food source remain intact. Analysis of 36 temperate
      lakes showed that shallow lakes have a higher potential for climate induced match
      mismatches, as the probability of active overwintering daphnids decreases with
      lake depth. Future research should point out whether lake depth is a direct
      causal factor in determining the presence of active overwintering daphnids or
      merely indicative for underlying causal factors such as fish predation and
      macrophyte cover.

PMID- 17024386
TI  - Temperature sensitivity of vertical distributions of zooplankton and
      planktivorous fish in a stratified lake.
AB  - Recent studies have indicated that temporal mismatches between interacting
      populations may be caused by consequences of global warming, for example rising
      spring temperatures. However, little is known about the impact of spatial
      temperature gradients, their vulnerability to global warming, and their
      importance for interacting populations. Here, we studied the vertical
      distribution of two planktivorous fish species (Coregonus spp.) and their
      zooplankton prey in the deep, oligotrophic Lake Stechlin (Germany). The night
      time vertical centre of gravity both of the fish populations and of two of their
      prey groups, daphnids and copepods, were significantly correlated to the
      seasonally varying water temperature between March and December 2005. During the
      warmer months, fish and zooplankton occurred closer to the surface of the lake
      and experienced higher temperatures. The Coregonus populations differed
      significantly in their centre of gravity; hence, also, the temperature
      experienced by the populations was different. Likewise, daphnids and copepods
      occurred in different water depths and hence experienced different temperatures
      at least during the summer months. We conclude that any changes in the vertical
      temperature gradient of the lake as a result of potential future global warming
      may impact the two fish populations differently, and may shape interaction
      strength and timing between fish and their zooplankton prey.

PMID- 17024387
TI  - Pollinator-mediated assortative mating in mixed ploidy populations of Chamerion
      angustifolium (Onagraceae).
AB  - Establishment of polyploid individuals within diploid populations is
      theoretically unlikely unless polyploids are reproductively isolated, pre
      zygotically, through assortative pollination. Here, we quantify the contribution
      of pollinator diversity and foraging behaviour to assortative pollen deposition
      in three mixed-ploidy populations of Chamerion angustifolium (Onagraceae).
      Diploids and tetraploids were not differentiated with respect to composition of
      insect visitors. However, foraging patterns of the three most common insect
      visitors (all bees) reinforced assortative pollination. Bees visited tetraploids
      disproportionately often and exhibited higher constancy on tetraploids in all
      three populations. In total, 73% of all bee flights were between flowers of the
      same ploidy (2x-2x, 4x-4x); 58% of all flights to diploids and 83% to tetraploids
      originated from diploid and tetraploid plants, respectively. Patterns of pollen
      deposition on stigmas mirrored pollinator foraging behaviour; 73% of all pollen
      on stigmas (70 and 75% of pollen on diploid and tetraploid stigmas, respectively)
      came from within-ploidy pollinations. These results indicate that pollinators
      contribute to high rates of pre-zygotic reproductive isolation. If patterns of
      fertilization track pollen deposition, pollinator-plant interactions may help
      explain the persistence and spread of tetraploids in mixed-ploidy populations.

PMID- 17024388
TI  - Introducing inter-individual growth variability in the assessment of a cephalopod
      population: application to the English Channel squid Loligo forbesi.
AB  - A new approach is presented here to better take into account inter-individual
      growth variability in age-structured models used for stock assessment. Cohort
      analysis requires knowledge of the age structure of the catch, generally derived
      from an age-length key and length-structure information. Age distribution at
      length is estimated by applying conditional quantile regression to a data set of
      lengths and ages estimated from calcareous parts. A "stochastic" age-length key
      that describes the probability of age-at-length is applied to the English Channel
      squid Loligo forbesi. Age distribution at length from quantile regression proved
      to be considerably less biased than that resulting from both polymodal
      decomposition (PD) and two separate slicing methods. Both catch-at-age and stock
      size were underestimated using classical methods. Estimations of fishing
      mortalities from classical methods were higher causing underestimation in yield
      simulations. Quantile regression offers a more complete statistical analysis of
      the stochastic relationships among random variables than mean regression and PD.

PMID- 17024389
TI  - Renal survival in pediatric patients with IgA nephropathy.

PMID- 17024390
TI  - MPGN II--genetically determined by defective complement regulation?
AB  - MPGN II is a rare disease which is characterized by complement containing
      deposits within the GBM. The disease is characterized by functional impairment of
      the GBM causing progressive loss of renal function eventually resulting in end
      stage renal disease. It now becomes evident that in addition to C3NeF, which
      inhibits the inactivation of the alternative C3 convertase C3bBb, different
      genetically determined factors are also involved in the pathogenesis of MPGN II.
      These factors though different from C3NeF also result in defective complement
      regulation acting either through separate pathways or synergistically with C3NeF.
      Following the finding of MPGN II in Factor H deficient animals, patients with
      MPGN II were identified presenting with an activated complement system caused by
      Factor H deficiency. Factor H gene mutations result in a lack of plasma Factor H
      or in a functional defect of Factor H protein. Loss of Factor H function can also
      be caused by inactivating Factor H autoantibodies, C3 mutations preventing
      interaction between C3 and Factor H, or autoantibodies against C3. Identification
      of patients with MPGN II caused by defective complement control may allow
      treatment by replacement of the missing factor via plasma infusion, thus possibly
      preventing or at least delaying disease progress.

PMID- 17024391
TI  - Clinical outcome in children with Henoch-Schonlein nephritis.
AB  - Henoch-Schonlein purpura (HSP) is the most common vasculitis in childhood. The
      long-term prognosis is variable and depends on renal involvement. The aim of this
      study was to evaluate both clinical features of the children with HSP and the
      prognoses of short- and long-term outcome of patients diagnosed as HSP nephritis
      (HSN). This is a retrospective data study of all children with HSP hospitalized
      from January 1991 to December 2005. The patients with HSN were classified
      according to their initial presentation, histologic findings, type of treatment
      and clinical outcome. All patients have been evaluated once every 2 months. Fifty
      three of the patients had kidney biopsies. The patient population consisted of
      141 children included 78 boys (55.3%) and 63 girls (44.7%) ranging in age at
      disease onset from 2 to 17 (8.9+/-3.29) years. Renal involvement was determined
      in 58.1%. Nephrotic and/or nephritic syndrome were found to be an unfavorable
      predictor both for short and long-term outcome (P<0.05). However, 35% of these
      patients and 62% of them showed complete remission after 6 months and long-term
      course. Overall prognosis of HSN is relatively good and long-term morbidity is
      predominantly associated with initial presentation and renal involvement.

PMID- 17024392
TI  - Power Doppler sonographic evaluation of acute childhood pyelonephritis.
AB  - Urinary tract infection is common in children. The available gold standard
      methods for diagnosis, Tc-99m dimercaptosuccinic acid (DMSA) scan and computed
      tomography (CT) are invasive and expensive. This study was performed to assess
      the role of power Doppler ultrasound (PDU) for diagnosis of acute pyelonephritis
      (APN) compared with Tc-99m DMSA scan. A prospective study was conducted in 34
      children with the mean age of 2.8+/-2.7 years who were hospitalized with the
      first episode of febrile urinary tract infection. All children were examined in
      the first 3 days of admission by PDU and Tc-99m DMSA scan. Patients with
      congenital structural anomaly were excluded. Each kidney was divided into three
      zones. The comparison between PDU and DMSA scan was performed on the basis of
      patients and renal units. According to the patient's number, sensitivity,
      specificity, positive and negative predictive values, and accuracy of PDU were
      89%, 53%, 70%, 80%, and 74%, respectively, but based on the renal units, changed
      to 66%, 81%, 46%, 91%, and 79%, respectively. Although PDU has the potential for
      identifying APN in children, it is still soon to replace DMSA scan.

PMID- 17024393
TI  - Mild course of Puumala nephropathy in children in an area with sporadic
      occurrence Hantavirus infection.
AB  - The first three children with Puumala virus nephropathy diagnosis in the Czech
      Republic are reported on. A boy and two girls were admitted with symptoms of
      interstitial nephritis. The medical history in all children revealed flu-like
      symptoms. All patients were mildly pyrexial and had elevated erythrocytes
      sedimentation rate, C-reactive protein and low hemoglobin levels. Serum
      creatinine levels were elevated and proteinuria exceeded 700 mg/L in all
      children. Tubular proteinuria, glycosuria, high urinary N-acetyl-beta-D
      glucosaminidase levels and alpha-1-microglobulin levels confirmed the tubular
      lesion. Renal biopsies revealed a uniform pattern and showed non-purulent
      interstitial nephritis in all patients. Puumala virus antigen antibodies were
      detected in the plasma. All patients were treated with steroids and urine
      abnormalities and renal function returned to normal within 4 weeks. Hantavirus
      infection should be considered as one of possible causes of interstitial
      nephritis with decreased GFR in children even in areas with a low incidence of
      this infection.

PMID- 17024394
TI  - Cyclosporin therapy in patients with Alport syndrome.
AB  - Alport syndrome (AS) is a hereditary disorder of type IV collagen characterized
      by the association of progressive hematuric nephritis and sensorineural hearing
      loss. An increase in proteinuria is linked with progressive renal failure.
      Preliminary data have shown that cyclosporin therapy reduces proteinuria, thereby
      suggesting that it may also slow the progression of AS nephropathy. We treated
      nine AS patients manifesting proteinuria >1 g/m(2)/day and a glomerular
      filtration rate (GFR) >50 ml/min/1.73 m(2) with cyclosporin for at least 6
      months. At the end of this 6-month period, mean proteinuria had decreased from
      2+/-1.06 to 0.65+/-0.73 g/day, and mean albuminemia had increased from 29+/-5.2
      to 35+/-6.5 g/l. Mean inulin clearance had decreased from 102+/-29 to 74+/-16.3
      ml/min/1.73 m(2). Cyclosporin treatment was stopped in four patients because of
      inefficacy or adverse effects and continued in the remaining five patients for an
      additional 14-42 months. At the end of this second treatment period, control
      renal biopsies revealed significant lesions of cyclosporin nephrotoxicity in
      three patients. Based on these results we conclude that while cyclosporin therapy
      can decrease proteinuria in most patients with AS, it may be associated with
      nephrotoxicity, thereby precluding its long-term use.

PMID- 17024396
TI  - Changes in the pollen seasons of the early flowering trees Alnus spp. and Corylus
      spp. in Worcester, United Kingdom, 1996-2005.
AB  - Previous work on Betula spp. (birch) in the UK and at five sites in Europe has
      shown that pollen seasons for this taxon have tended to become earlier by about 5
      10 days per decade in most regions investigated over the last 30 years. This
      pattern has been linked to the trend to warmer winters and springs in recent
      years. However, little work has been done to investigate the changes in the
      pollen seasons for the early flowering trees. Several of these, such as Alnus
      spp. and Corylus spp., have allergens, which cross-react with those of Betula
      spp., and so have a priming effect on allergic people. This paper investigates
      pollen seasons for Alnus spp. and Corylus spp. for the years 1996-2005 at
      Worcester, in the West Midlands, United Kingdom. Pollen data for daily average
      counts were collected using a Burkard volumetric trap sited on the exposed roof
      of a three-story building. The climate is western maritime. Meteorological data
      for daily temperatures (maximum and minimum) and rainfall were obtained from the
      local monitoring sites. The local area up to approximately 10 km surrounding the
      site is mostly level terrain with some undulating hills and valleys. The local
      vegetation is mixed farmland and deciduous woodland. The pollen seasons for the
      two taxa investigated are typically late December or early January to late March.
      Various ways of defining the start and end of the pollen seasons were considered
      for these taxa, but the most useful was the 1% method whereby the season is
      deemed to have started when 1% of the total catch is achieved and to have ended
      when 99% is reached. The cumulative catches (in grains/m(3)) for Alnus spp.
      varied from 698 (2001) to 3,467 (2004). For Corylus spp., they varied from 65
      (2001) to 4,933 (2004). The start dates for Alnus spp. showed 39 days difference
      in the 10 years (earliest 2000 day 21, latest 1996 day 60). The end dates
      differed by 26 days and the length of season differed by 15 days. The last 4
      years in the set had notably higher cumulative counts than the first 2, but there
      was no trend towards earlier starts. For Corylus spp. start days also differed by
      39 days (earliest 1999 day 5, latest 1996 day 44). The end date differed by 35
      days and length of season by 26 days. Cumulative counts and lengths of season
      showed a distinct pattern of alternative high (long) and low (short) years. There
      is some evidence of a synchronous pattern for Alnus spp.. These patterns show
      some significant correlations with temperature and rainfall through the autumn,
      winter and early spring, and some relationships with growth degree 4s and chill
      units, but the series is too short to discern trends. The analysis has provided
      insight to the variation in the seasons for these early flowering trees and will
      form a basis for future work on building predictive models for these taxa.

PMID- 17024397
TI  - A synoptic climatology of pollen concentrations during the six warmest months in
      Sydney, Australia.
AB  - This paper takes an air mass approach to investigating the influence of weather
      on pollen concentrations in the atmosphere in Sydney, Australia, by producing a
      synoptic classification of pollen concentrations measured in the Sydney Basin.
      This synoptic classification has been produced using multivariate statistical
      techniques including principal component analysis and cluster analysis, to assign
      days into meteorologically homogenous categories. Surface and upper air
      meteorological data for warm months (October-March) over a 10-year period were
      used as input into the statistical analyses. Eleven synoptic categories were
      found in Sydney during the warm months. Pollen concentrations for the total
      pollen load and five individual families measured over a 3.5-year period have
      been investigated for each of the synoptic categories. High pollen concentrations
      during the warm months in Sydney are found to be influenced by the presence of a
      region of low surface pressure located to the south of the continent, bringing
      fast dry westerly gradient winds to Sydney. It is envisaged that these results
      will be important from a pollen forecast and associated public health
      perspective.

PMID- 17024398
TI  - A survey of public perception and response to heat warnings across four North
      American cities: an evaluation of municipal effectiveness.
AB  - To examine the efficacy of municipal heat watch warning systems, a thorough
      evaluation of the heat mitigation plans of four North American cities--Dayton
      (Ohio, USA), Philadelphia (Pennsylvania, USA), Phoenix (Arizona, USA), and
      Toronto (Ontario, Canada)--was undertaken. In concert with this evaluation was a
      survey of residents in the metropolitan areas of these cities that gauged their
      perception of their own vulnerability to the heat, as well as their knowledge of
      heat warnings and the activities recommended to be undertaken to help mitigate
      the effects of the heat. In total, 908 respondents participated in the telephone
      survey. Some of the key results indicate that knowledge of the heat warning was
      nearly universal (90%), and likely due to pervasive media coverage more than any
      other means. Though knowledge of the event was widespread, knowledge of what to
      do was less common. Only around half of all respondents mentioned that they
      changed their behavior, and despite the diversity of information available on
      mitigating heat vulnerability, most respondents stated that they merely "avoided
      the outdoors" at all costs. Though air conditioning was nearly ubiquitous among
      respondents, over a third mentioned that economic factors of energy costs were
      considered in terms of how long or whether the air conditioner was turned on.

PMID- 17024399
TI  - The effects of slight pressure oscillations in the far infrasound frequency range
      on the pars flaccida in gerbil and rabbit ears.
AB  - This study was designed to clarify whether the pars flaccida (PF) as a flexible
      part of the tympanic membrane is capable of reacting to pressure oscillations
      (PO) with amplitudes and frequencies typical for natural atmospheric pressure
      fluctuations in the far infrasound frequency range (APF). If so, the PF
      mechanical reactions to APF might be involved in the overall physiologic
      regulation processes, which make organisms susceptible to APF. The displacements
      of the PF in response to PO were measured in vitro in ears of gerbils and rabbits
      by means of laser Doppler vibrometry. The index of the PF reactivity (R(a)) was
      determined as the ratio of the amplitude of the PF oscillations (PFO) to the
      amplitude of the PO. All kinds of PO applied caused PFO. The amplitude of the PFO
      increased when the amplitude of the PO was increased. In gerbils, a decrease in
      R(a) with the increase in amplitude of the PO was observed. In the range of PO
      lowest amplitudes (4-20 Pa) R(a) proved to be 1.4 times higher than in the range
      of highest amplitudes (90-105 Pa). Considering that the natural APF are usually
      within the range of +/-20 Pa, this fact points to an important contribution of
      the PF to the pressure dynamics in the middle ear (ME) of gerbils. In rabbit
      ears, R(a) was lower and recovery from plastic deformation was slower than in
      gerbils. Our findings are in line with the suggestion that the PF might play an
      important role in respect of adaptation to natural APF.

PMID- 17024400
TI  - Computer-assisted screw insertion for cervical disorders in rheumatoid arthritis.
AB  - To reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical
      lesions, the authors have been using C1/2 transarticular and cervical pedicle
      screw fixations. Pedicle screw fixation and C1/2 transarticular screw fixation
      are biomechanically superior to other fixation techniques for RA patients.
      However, due to severe spinal deformity and small anatomical size of the
      vertebra, including the lateral mass and pedicle, in the most RA cervical
      lesions, these screw fixation procedures are technically demanding and pose the
      potential risk of neurovascular injuries. The purpose of this study was to
      evaluate the accuracy and safety of cervical pedicle screw insertion to the
      deformed, fragile, and small RA spine lesions using computer-assisted image
      guidance systems. A frameless, stereotactic image-guidance system that is CT
      based, and optoelectronic was used for correct screw placement. A total of 21
      patients (16 females, 5 males) with cervical disorders due to RA were surgically
      treated using the image-guidance system. Postoperative computerized tomography
      and plane X-ray was used to determine the accuracy of the screw placement. Neural
      and vascular complications associated with screw insertion and postoperative
      neural recovery were evaluated. Postoperative radiological evaluations revealed
      that only 1 (2.1%; C4) of 48 screws inserted into the cervical pedicle had
      perforated the vertebral artery canal more than 25% (critical breach). However,
      no neurovascular complications were observed. According to Ranawat's
      classification, 9 patients remained the same, and 12 patients showed improvement.
      Instrumentation failure, loss of reduction, or nonunion was not observed at the
      final follow-up (average 49.5 months; range 24-96 months). In this study, the
      authors demonstrated that image-guidance systems could be applied safely to the
      cervical lesions caused by RA. Image-guidance systems are useful tools in
      preoperative planning and in transarticular or transpedicular screw placement in
      the cervical spine of RA patients.

PMID- 17024401
TI  - More than 20-year follow-up Harrington instrumentation in the treatment of severe
      idiopathic scoliosis.

PMID- 17024402
TI  - Critical ischemia time in a model of spinal cord section. A study performed on
      dogs.
AB  - Vascular changes after acute spinal cord trauma are important factors that
      predispose quadriplegia, in most cases irreversible. Repair of the spinal blood
      flow helps the spinal cord recovery. The average time to arrive and perform
      surgery is 3 h in most cases. It is important to determine the critical ischemia
      time in order to offer better functional prognosis. A spinal cord section and
      vascular clamping of the spinal anterior artery at C5-C6 model was used to
      determine critical ischemia time. The objective was to establish a critical
      ischemia time in a model of acute spinal cord section. Four groups of dogs were
      used, anterior approach and vascular clamp of spinal anterior artery with 1, 2,
      3, and 4 h of ischemia and posterior hemisection of spinal cord at C5-C6 was
      performed. Clinical evaluation was made during 12 weeks and morphological
      evaluation at the end of this period. We obtained a maximal neurological
      coordination at 23 days average. Two cases showed sequels of right upper limb
      paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h
      of ischemia. Morphological examination showed 25% of damaged area. The VIII and
      IX Rexed's laminae were the most affected. The critical ischemia time was 3 h.
      Dogs with 4 h did not exhibit any recovery.

PMID- 17024403
TI  - A theoretical study of some new analogues of the anti-cancer drug camptothecin.
AB  - The enzyme topoisomerase I (topo I), which is essential for cell replication,
      transiently causes a DNA single strand break and makes a complex with it. The
      anti-cancer agent camptothecin (CPT) binds to the topo I-DNA complex and
      stabilizes it, preventing resealing of the broken DNA strand and cell growth.
      Considering the structural factors of CPT that are believed to be involved in
      stabilizing the topo I-DNA complex via hydrogen bonding and stacking
      interactions, designs of two new analogues of CPT (topo I inhibitors) have been
      suggested. The molecular geometries of CPT, two of its analogues and certain
      other related molecules included in the study were fully optimized in both gas
      phase and aqueous media at the B3LYP/6-311++G(d,p) level of density functional
      theory. Solvation effects of aqueous media were treated using the polarizable
      continuum model (PCM). Net CHelpG charges and surface molecular electrostatic
      potentials (MEP) near the atomic sites of the molecules were studied. Structural
      analogy and surface MEP values suggests that the two new CPT analogues studied
      here would be potent topoisomerase I inhibitors.

PMID- 17024404
TI  - Investigation of the structure of 6-amino-4-methylamino-5-nitrosopyrimidine by X
      ray diffraction, NMR and molecular modeling.
AB  - The structure of 6-amino-4-methylamino-5-nitrosopyrimidine in the solid state and
      dimethylsulfoxide solution was investigated using single crystal X-ray
      diffraction and (1)H, (13)C NMR spectroscopy methods. Hartree-Fock (HF) and
      density functional (DFT) levels of theory were used to interpret the experimental
      data obtained by X-ray and NMR methods.

PMID- 17024405
TI  - LigPath: a module for predictive calculation of a ligand's pathway into a
      receptor-application to the gpH1-receptor.
AB  - Until now, the access of ligands into the binding pocket of a G-protein coupled
      receptor has scarcely been studied using molecular-modeling techniques because of
      the lack of sufficient algorithms. Neither with Monte-Carlo- nor with Molecular
      Dynamics Simulations can the penetration of a ligand into the binding pocket of a
      receptor be calculated because of the excessive amount of computing time needed.
      Therefore, a new algorithm LigPath for approximate calculation of a ligand's
      pathway into the binding pocket has been developed. This new algorithm is based
      on a linkage of directional guiding of the ligand, Monte-Carlo-Search and
      minimization. In order to evaluate the performance of the algorithm, the guinea
      pig histamine H(1) receptor was investigated in combination with one of its
      potent agonists, histaprodifen, which is proposed to bind in a pocket deep
      between the transmembrane helices of the receptor. Our calculations show that the
      amino acids Tyr194, Phe193, Phe436 and Phe433 guide the positively charged
      histaprodifen from the extracellular part of the receptor into the binding
      pocket.

PMID- 17024406
TI  - Pt-bridges in various single-strand and double-helix DNA sequences. DFT and MP2
      study of the cisplatin coordination with guanine, adenine, and cytosine.
AB  - In this study, various platinum cross-links in DNA bases were explored. Some of
      these structures occur in many cis/trans-platinated double-helixes or single
      stranded adducts. However, in the models studied, no steric hindrance from sugar
      phosphate backbone or other surroundings is considered. Such restrictions can
      change the bonding picture partially but hopefully the basic energy
      characteristics will not be changed substantially. The optimization of the
      structures explored was performed at the DFT level with the B3LYP functional and
      the 6-31G(d) basis set. Perturbation theory at the MP2/6-31++G(2df,2pd) level was
      used for the single-point energy and 6-31+G(d) basis set for the electron
      property analyses. It was found that the most stable structures are the diguanine
      complexes followed by guanine-cytosine Pt-cross-links, ca 5 kcal mol(-1) less
      stable. The adenine-containing complexes are about 15 kcal mol(-1) below the
      stability of diguanine structures. This stability order was also confirmed by the
      BE of Pt-N bonds. For a detailed view on dative and electrostatic contributions
      to Pt-N bonds, Natural Population Analysis, determination of electrostatic
      potentials, and canonical Molecular Orbitals description of the examined systems
      were used.

PMID- 17024407
TI  - A hydrophobic similarity analysis of solvation effects on nucleic acid bases.
AB  - We investigate the changes in the solvation properties of the natural nucleic
      acid bases due to the formation of the canonical Watson-Crick hydrogen-bonded
      complexes. To this end, the changes in the free energy of solvation of the bases
      induced upon hydrogen-bonded dimerization are analyzed by means of the
      hydrophobic similarity index, which relies on the atomic contributions to the
      free energy of solvation determined by the partitioning method implemented in the
      framework of the MST continuum model. Such an index is also used to examine the
      hydrophobic similarity between the canonical nucleic acid bases and a series of
      highly apolar analogues, which have been designed as potential candidates to
      expand the genetic alphabet. The ability of these analogues to be incorporated
      into modified DNA duplexes can be related to the large reduction in the
      hydrophilicity of the natural bases upon formation of the canonical hydrogen
      bonded dimers. The results illustrate the suitability of the hydrophobic
      similarity index to rationalize the role played by solvation in molecular
      recognition.

PMID- 17024408
TI  - Natural orbitals for chemical valence as descriptors of chemical bonding in
      transition metal complexes.
AB  - Natural orbitals for chemical valence (NOCV) are defined as the eigenvectors of
      the chemical valence operator defined by Nalewajski et al.; they decompose the
      deformation density (differential density, Deltarho) into diagonal contributions.
      NOCV were used in a description of the chemical bond between the organometallic
      fragment and the ligand in example transition-metal complexes: heme-CO
      ([FeN(5)C(20)H(15)]-CO), [Ni-diimine hydride]-ethylene ([N;N-Ni-H]-C(2)H(4), N;N
      = -NH-CH-CH-NH-), and [Ni(NH(3))(3)]-CO. DFT calculations were performed using
      gradient-corrected density functional theory (DFT) in the fragments resolution,
      using the fragment/ligand Kohn-Sham orbitals as a basis set in calculations for
      the whole fragment-ligand complex. It has been found that NOCV lead to a very
      compact description of the fragment-ligand bond, with only a few orbitals
      exhibiting non-zero eigenvalues. Results of NOCV analysis, compared with Mulliken
      populations analysis and Zigler-Rauk interaction-energy decomposition,
      demonstrate that the use of the natural valence orbitals allows for a separation
      of the sigma-donation and pi-back-donation contributions to the ligand-fragment
      bond. They can be also useful in comparison of these contributions in different
      complexes.

PMID- 17024409
TI  - Molecular surface electrostatic potentials and anesthetic activity.
AB  - General anesthetics apparently act through weak, noncovalent and reversible
      interactions with certain sites in appropriate brain proteins. As a means of
      gaining insight into the factors underlying anesthetic potency, we have analyzed
      the computed electrostatic potentials V (S)(r) on the surfaces of 20 molecules
      with activities that vary between zero and high. Our results are fully consistent
      with, and help to interpret, what has been observed experimentally. We find that
      an intermediate level of internal charge separation is required; this is measured
      by Pi, the average absolute deviation of V (S)(r), and the approximate window is
      7 < Pi < 13 kcal mol(-1). This fits in well with the fact that anesthetics need
      to be lipid soluble, but also to have some degree of hydrophilicity. We further
      show that polyhalogenated alkanes and ethers, which include the most powerful
      known anesthetics, have strong positive potentials, V (S,max), associated with
      their hydrogens, chlorines and bromines (but not fluorines). These positive sites
      may impede the functioning of key brain proteins, for example by disrupting their
      normal hydrogen-bond patterns. It has indeed been recognized for some time that
      the most active polyhalogenated alkanes and ethers contain hydrogens usually in
      combination with chlorines and/or bromines.

PMID- 17024410
TI  - A three-dimensional model of the human transglutaminase 1: insights into the
      understanding of lamellar ichthyosis.
AB  - The stratum corneum, the outer layer of the epidermis, serves as a protective
      barrier to isolate the skin from the external environment. Keratinocyte
      transglutaminase 1 (TGase 1) catalyzes amide crosslinking between glutamine and
      lysine residues on precursor proteins forming the impermeable layers of the
      epidermal cell envelopes (CE), the highly insoluble membranous structures of the
      stratum corneum. Patients with the autosomal recessive skin disorder lamellar
      ichthyosis (LI) appear to have deficient cross-linking of the cell envelope due
      to mutations identified in TGase 1, linking this enzyme to LI. In the absence of
      a crystal structure, molecular modeling was used to generate the structure of
      TGase 1. We have mapped the known mutations of TGase 1 from our survey obtained
      from a search of PubMed and successfully predicted the impact of these mutations
      on LI. Furthermore, we have identified Ca(2+) binding sites and propose that
      Ca(2+) induces a cis to trans isomerization in residues near the active site as
      part of the enzyme transamidation activation. Docking experiments suggest that
      substrate binding subsequently induces the reverse cis to trans isomerization,
      which may be a significant part of the catalytic process. These results give an
      interpretation at the molecular level of previously reported mutations and lead
      to further insights into the structural model of TGase 1, providing a new basis
      for understanding LI.

PMID- 17024411
TI  - Theoretical studies of the reduction reaction of the anti-tumor drug FR900482.
AB  - A number of analogs of the anti-tumor drug FR900482 have been investigated with
      quantum chemical calculations, at the HF/6-31G(d,p) and B3LYP levels from the
      point of view of their energy, optimum geometry and the energetics of the
      reduction reaction. It was found that the parent molecule is the most prone to
      reduction, followed closely by fluorine-containing analogs.

PMID- 17024412
TI  - SOMMER: self-organising maps for education and research.
AB  - SOMMER is a publicly available, Java-based toolbox for training and visualizing
      two- and three-dimensional unsupervised self-organizing maps (SOMs). Various map
      topologies are implemented for planar rectangular, toroidal, cubic-surface and
      spherical projections. The software allows for visualization of the training
      process, which has been shown to be particularly valuable for teaching purposes.

PMID- 17024413
TI  - A collagen-based interface construct for the assessment of cell-dependent
      mechanical integration of tissue surfaces.
AB  - The interface between any newly engineered tissue and pre-existing tissue is of
      great importance to tissue engineering; however, this process has so far been
      largely ignored, with few reports regarding the mechanical strength of newly
      integrated connective tissues surfaces. A new model system has been developed to
      generate a well-defined interface between two collagen lattices: one pre
      contracted by resident fibroblasts and the other a cell-free wrapping gel. This
      construct can be cultured for prolonged periods (>2 weeks) and can also be fitted
      onto a mechanical testing system to measure the interface adhesive strength at
      the end of the culture time. Interface adhesive strength shows a six-fold
      increase after 1 week in culture, compared with the time-zero baseline.
      Observations of cell migration across the interface suggest that cell
      translocation in the three-dimensional matrix might play an important role in the
      integration process. In this new controlled geometry, normal and shear stresses
      at the interface can be analysed by finite element modelling and the areas at
      which debonding starts can be defined. The current experimental design permits
      solid multiple (homogeneous or heterogeneous) interface formation in vitro with a
      well-defined geometry and the possibility of measuring mechanical linkage. This
      design should enable many other factors affecting cell-driven interface
      strengthening to be investigated.

PMID- 17024414
TI  - Expression of glial progenitor markers p75NTR and S100 protein in the developing
      mouse parathyroid gland.
AB  - Drosophila glial cells missing (Drosophila Gcm) is a transcription factor that is
      required for the differentiation of glial cells. Gcm2, a mouse homologue of
      Drosophila Gcm, is a master regulatory gene of parathyroid development and is
      expressed in the parathyroid rudiment. We have found that the mouse parathyroid
      exhibits the glial progenitor markers, p75(NTR) and S100 protein, during fetal
      development. At embryonic day 11.5 (E11.5), a bulge of the parathyroid rudiment
      is formed in the cranial part of the third pharyngeal pouch. The rudiment
      exhibits immunoreactivity for p75(NTR) and S100 protein, in addition to secretory
      protein 1/chromogranin A. While the thymus rudiment, which arises from the caudal
      part of the third pharyngeal pouch, is moving downwards, the parathyroid is
      attached to the top of thymus. The parathyroid comes into contact with the
      thyroid lobe at E13.5 and then separates from the thymus. The parathyroid
      maintains intense immunoreactivity for p75(NTR) and S100 protein during the
      migration and development in the thyroid lobe. The co-localization of p75(NTR)
      and S100 in the developing parathyroid cells has been confirmed by confocal
      microscopy. Other glial markers, viz. glial fibrillary acidic protein, Sox10,
      vimentin and nestin, are not expressed in the parathyroid at any stage of
      development. The neural progenitor markers, neurofilament 160 and TuJ1, are also
      absent from the parathyroid. Taken together, we suggest that Gcm2 supplies only
      some glial progenitor characteristics to the parathyroid rudiment.

PMID- 17024415
TI  - Derivation of muscles of the Aristotle's lantern from coelomic epithelia.
AB  - Transmission electron microscopy was employed to study structural changes in the
      lantern muscles occurring during the transition from young to adult in the sea
      urchin Strongylocentrotus nudus. A comparative examination of four major lantern
      muscles (compass depressors, compass elevators, protractors and retractors)
      suggests that myogenesis involves four consecutive stages. At the initial stage,
      the muscles show the organization of a mesentery delimited by pseudostratified
      coelomic epithelia, which are composed of peritoneal cells spanning the whole
      height of each epithelium, and myoepithelial cells, which are clustered together
      to fill the interstices between the basal processes of the peritoneal cells.
      During the next stage, the clusters of myoepithelial cells partly "sink" into the
      underlying connective tissue. At the third stage of muscularization, the
      myoepithelial cells increase in size and further invade the underlying connective
      tissue so that the myoepithelium splits into an apical peritoneal layer and a
      deeper mass of myoepithelial cells immersed in the connective tissue. However,
      these two layers are connected by a continuous basal lamina. This is thus the
      first description of an intermediate developmental stage between pseudostratified
      myoepithelim and genuine echinoderm muscles. For such a myoepithelium, we propose
      the term "immersed myoepithelium". At the most advanced stage of myogenesis, the
      myocytes detach completely from the epithelium to form subepithelial muscle
      bundles. Myogenesis in the sea urchin takes a long time during which continuous
      myogenic differentiation occurs in the coelomic epithelium and the newly formed
      myocytes and associated neurons penetrate into the underlying connective tissue.

PMID- 17024416
TI  - Injections of leptin into rat ventromedial hypothalamus increase adipocyte
      apoptosis in peripheral fat and in bone marrow.
AB  - The accumulation of fat cells (adipocytes) in bone marrow is now thought to be a
      factor contributing to age-related bone loss. Women with osteoporosis have higher
      numbers of marrow adipocytes than women with healthy bone, and bone formation
      rate is inversely correlated with adipocyte number in bone tissue biopsies from
      both men and women. Adipogenic differentiation of bone marrow stromal cells
      increases with age, but the factors regulating populations of mature adipocytes
      are not well understood. Leptin is thought to regulate adipose tissue mass via
      its receptors in the ventromedial hypothalamus (VMH). We have therefore tested
      the hypothesis that stimulation of leptin receptors in the VMH regulates
      adipocyte number in bone marrow. Results indicate that unilateral twice-daily
      injections of leptin into the rat VMH for only 4 or 5 days cause a significant
      reduction in the number of adipocytes in peripheral fat pads and bone marrow and
      indeed eliminate adipocytes almost entirely from bone marrow of the proximal
      tibia. Osteoblast surface is not affected with leptin treatment. Apoptosis assays
      performed on bone marrow samples from control and treated rats have revealed a
      significant increase in protein concentration of the apoptosis marker caspase-3
      with leptin treatment. We conclude that stimulation of leptin receptors in the
      VMH significantly decreases the adipocyte population in bone marrow, primarily
      through apoptosis of marrow adipocytes. Elimination of marrow adipocytes via this
      central pathway may represent a useful strategy for the treatment and prevention
      of osteoporosis.

PMID- 17024417
TI  - Co-factors and co-repressors of Engrailed: expression in the central nervous
      system and cerci of the cockroach, Periplaneta americana.
AB  - In the larval cockroach (Periplaneta americana), knockout of Engrailed (En) in
      the medial sensory neurons of the cercal sensory system changes their axonal
      arborization and synaptic specificity. Immunocytochemistry has been used to
      investigate whether the co-repressor Groucho (Gro; vertebrate homolog: TLE) and
      the co-factor Extradenticle (Exd; vertebrate homolog: Pbx) are expressed in the
      cercal system. Gro/TLE is expressed ubiquitously in cell nuclei in the embryo,
      except for the distal pleuropodia. Gro is expressed in all nuclei of the thoracic
      and abdominal central nervous system (CNS) of first instar larva, although some
      neurons express less Gro than others. Cercal sensory neurons express Gro protein,
      which might therefore act as a co-repressor with En. Exd/Pbx is expressed in the
      proximal portion of all segmental appendages in the embryo, with the exception of
      the cerci. In the first instar CNS, Exd protein is expressed in subsets of
      neurons (including dorsal unpaired medial neurons) in the thoracic ganglia, in
      the first two abdominal ganglia, and in neuromeres A8-A11 of the terminal
      ganglion. Exd is absent from the cerci. Because Ultrabithorax/Abdominal-A
      (Ubx/Abd-A) can substitute for Exd as En co-factors in Drosophila, Ubx/Abd-A
      immunoreactivity has also been investigated. Ubx/Abd-A immunostaining is present
      in abdominal segments of the embryo and first instar CNS as far caudal as A7 and
      faintly in the T3 segment. However, Ubx/Abd-A is absent in the cerci and their
      neurons. Thus, in contrast to its role in Drosophila segmentation, En does not
      require the co-factors Exd or Ubx/Abd-A in order to control the synaptic
      specificity of cockroach sensory neurons.

PMID- 17024418
TI  - A comprehensive study of the spatial and temporal expression of the col5a1 gene
      in mouse embryos: a clue for understanding collagen V function in developing
      connective tissues.
AB  - Collagen V is a quantitatively minor component of collagen I fibrils and the
      defective product of classic Ehlers-Danlos syndrome (EDS). To provide new
      insights into its embryonic function, a continuous evaluation of the expression
      pattern of proalpha1(V), a chain common to all collagen V molecular forms, was
      performed by in situ hybridization of developing mouse from 7.5 days after
      conception (dpc) to birth. Proalpha1(V) transcripts were first detected at 8.5
      dpc, signals being considerably augmented at 16.5 dpc and declining at birth.
      Hybridization signals were, at first, exclusively detected in the dorsal aorta
      wall, heart, and adnexa. At 10.5 dpc, col5a1 expression was found in the heart,
      dorsal aorta wall, branchial arches, mesonephrotic tubules, and intestinal
      mesenchyme and coincided with proalpha1(I) developmental expression. Later stages
      exhibited an intense signal in more restricted regions, notably the skin, the
      bones and vertebral column, the cornea, the tendons and ligaments, the peritoneal
      membranes, the umbilical cord, and the salivary gland. The data revealed the
      important contribution of collagen V to the development of functional connective
      tissues. Proalpha1(V) signals were exclusively detected in the flattened cells of
      the surface ectoderm at 10.5 dpc. By 12.5 dpc, when cells had become cuboidal,
      the signal switched to the dermal fibroblasts. Thus, type V collagen appears to
      contribute to epidermis differentiation. Our data also suggest that collagen V
      participates in bone formation and/or mineralization and in the renewal of
      stromal cells in the cornea. The results underscore the role of collagen V in
      developing embryos and provide important clues for analyzing the phenotype of
      mouse models for EDS.

PMID- 17024419
TI  - Ultrastructural immunolocalization of IGF-1 and insulin receptors in rat
      pituitary culture: evidence of a functional interaction between gonadotroph and
      lactotroph cells.
AB  - We have investigated the expression of receptors for insulin and insulin-like
      growth factor 1 (IGF-1) in rat pituitary cells in vitro and examined the
      morphological and proliferative changes induced in adenohypophyseal cells by
      insulin and IGF-1. The proliferation of lactotrophs was determined by double
      immunostaining for bromodeoxyuridine and prolactin. Incubation with insulin (10,
      100 or 1000 ng/ml) or IGF-1 (5, 30 or 100 ng/ml) for 48 or 72 h significantly
      increased the number of lactotrophs undergoing mitosis. Co-incubation of insulin
      or IGF-1 with genistein (25 microM), an inhibitor of the tyrosine kinase
      receptor, reduced the proliferation of lactotrophs elicited by the hormone and
      the growth factor. The receptors for insulin and IGF-1 were localized in intact
      pituitary cells by ultrastructural immunocytochemistry with the colloidal gold
      protein A technique. Gonadotrophs expressed both receptors, specific labelling
      being restricted to this cell type. Electron-microscopical observations of
      pituitary cell cultures incubated with insulin or IGF-1 revealed gonadotroph
      cells exhibiting the fine-structural features of enhanced protein synthetic
      activity. These findings suggest that both insulin and IGF-1 are able to induce
      the proliferation of lactotrophs through an indirect mechanism mediated by a
      factor synthesized by gonadotroph cells, in addition to stimulating the
      biosynthetic activity of the gonadotroph in a direct manner.

PMID- 17024420
TI  - Use of microarrays to find novel regulators of periodontal ligament fibroblast
      differentiation.
AB  - Periodontal regeneration requires the coordinated movement and differentiation of
      several cell types in order to re-establish the cementum, periodontal ligament
      (PDL), and alveolar bone. Cells in culture are often used as model systems for
      mature tissues, although they may represent expanded progenitor cell populations.
      Comparison of transcript expression between fresh PDL tissue and PDL cell
      isolates by MicroArray analysis has revealed numerous molecular differences.
      Several transcripts (including alkaline phosphatase, bone sialoprotein,
      periostin, and fibromodulin) are expressed at higher levels in fresh PDL than in
      cultured PDL cells. In contrast, PDL cells in culture selectively express a
      variety of growth factors. Several of these growth factors alter PDL fibroblast
      behavior. Two members of the transforming growth factor beta family of growth
      factors, namely, bone morphogenic protein-7 (BMP7) and growth differentiation
      factor-5 (GDF5), reduce cell proliferation and Stro-1 expression (a bone marrow
      stromal stem cell marker), whereas only BMP7 induces alkaline phosphatase
      activity. In contrast, fibroblast growth factor-5 induces enhanced cell
      proliferation and Stro-1 expression, while repressing alkaline phosphatase
      activity. The stimulation of PDL cells to differentiate (either by BMP7 or GDF5)
      inhibits cell motility. Thus, PDL cells in culture are regulated by several
      factors that differentially stimulate a mineralized (cementoblast-like) fate, a
      non-mineralized fate (mature fibroblasts), or the propagation of a more naive
      phenotype (potential progenitors).

PMID- 17024421
TI  - Secretory cells of the airway express molecules of the chemoreceptive cascade.
AB  - Airway secretion is maintained by specialized non-ciliated epithelial cells whose
      phenotype varies with their topographical location. In addition, specialized
      epithelial cells located in the airway contain the molecular machinery of
      chemoreceptive elements. Our aim has been to evaluate whether the secretory cells
      themselves possess a chemoreceptive capability, which requires the simultaneous
      presence of chemosensory and secretory mechanisms. We performed
      immunohistochemical analysis with antibodies against the Clara-cell-specific
      secretory proteins, CC10 and CC26, as secretory markers. As chemoreceptive
      markers, we employed antibodies against alpha-gustducin and phospholipase C beta
      2 (PLCbeta2), two components of the taste transduction pathway. We also attempted
      to characterize further the secretory cell type by using a marker of chloride
      secretion, cystic fibrosis transmembrane regulator (CFTR). We found alpha
      gustducin localized in non-ciliated cells of the epithelium lining the trachea
      and bronchioles of adult rats, where it was also co-expressed with CC10 and CC26.
      Ultrastructural immunohistochemistry revealed alpha-gustducin in the apical
      cytoplasm of secretory cells, concentrated around and inside the granules. CFTR
      was also observed in a subpopulation of non-ciliated epithelial cells, co
      localized with some alpha-gustducin- and PLCbeta2-immunoreactive cells, at all
      levels of the airway epithelium. We conclude that non-ciliated epithelial cells
      of the rat airway express components of distinct signaling mechanisms and suggest
      that secretory events are driven by a molecular mechanism activated by the
      binding of luminal substances to G-protein-coupled receptors.

PMID- 17024422
TI  - Identification and expression analysis of rainbow trout pumilio-1 and pumilio-2.
AB  - Pumilio is a sequence-specific RNA-binding protein that regulates translation
      from the relevant mRNA. The PUF-domain, the RNA-binding motif of Pumilio, is
      highly conserved across species. In the present study, we have identified two
      pumilio genes (pumilio-1 and pumilio-2) in rainbow trout and analyzed their
      expression patterns in its tissues. Pumilio-1 mRNA and pumilio-2A mRNA code for
      typical full length Pumilio proteins that contain a PUF-domain, whereas pumilio
      2B mRNA is a splice variant of pumilio-2 and encodes a protein that lacks the PUF
      domain. We have also identified a novel 72-bp exon that has not been reported in
      other animal species but is conserved in fish species. The insertion of this
      novel exon leads to the expression of an isoform of the Pumilio-2 protein with a
      slightly altered conformation of the PUF-domain. Pumilio-1 mRNA and pumilio-2A
      mRNA (irrespective of the presence of the 72-bp exon) are expressed in both the
      brain and ovaries at high levels, whereas pumilio-2B mRNA is expressed at low
      levels in all the rainbow trout tissues examined. Western blot analysis also
      indicates that the full length Pumilio proteins are expressed predominantly in
      the brain and ovaries. These data suggest that the Pumilio proteins have
      physiological roles and are involved in regulatory mechanisms in rainbow trout.

PMID- 17024423
TI  - Proliferating activity in columnar cell lesions of the breast.
AB  - With the introduction of mammographic screening, columnar cell lesions (CCLs) are
      observed more and more frequently because they are often associated with
      microcalcifications. Until now, the proliferative activity of these lesions has
      not been previously evaluated. Ki67 index was performed by immunohistochemistry
      in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell
      hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia
      (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade
      intraductal carcinoma (DIN 2-3 n = 20). Adjacent terminal duct-lobular unit
      (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low
      and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and
      paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA,
      in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean
      8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS).
      Lastly, the Ki67 index is higher in DIN 2-3 (mean 25.4%) than in CCLs without
      atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells
      with columnar configuration but different proliferative characteristics. These
      data represent findings of biological interest which could help us to better
      understand these controversial lesions.

PMID- 17024424
TI  - Liver glycogen bodies: ground-glass hepatocytes in transplanted patients.
AB  - Ground-glass hepatocytes have been described in Lafora's disease, fibrinogen
      deposition, hepatitis B, type IV glycogenosis, and alcohol aversion (cyanamide)
      therapy. We encountered ground-glass hepatocytes with intracytoplasmic inclusions
      in four liver biopsies from three transplanted patients who had none of the above
      mentioned underlying diseases. One patient was a 4-year-old boy who had a kidney
      transplant for severe ureterovesical reflux. Patient 2 was a 52-year-old man who
      had two liver transplants because of hepatitis C. The third patient was a 7-month
      old girl who underwent a multivisceral transplant because of necrotizing
      enterocolitis and liver failure induced by total parenteral nutrition. The
      patients developed liver abnormalities from 45 days to 4 years after their
      transplants. The livers showed conspicuous ground-glass hepatocytes in 90% of the
      children's samples and 30% of the adult liver cells. The cytoplasmic bodies
      stained strongly for Gomori methenamine-silver; they were positive for periodic
      acid-Schiff without diastase, but negative after diastase digestion. They were
      negative for colloidal iron and hepatitis B core and surface antigens. Electron
      microscopy revealed non-membrane bound aggregates of glycogen. Idiopathic ground
      glass hepatocytes occur in transplanted patients and represent accumulation of
      altered glycogen. However, their clinical significance and cause are not entirely
      elucidated.

PMID- 17024425
TI  - Expression of E-cadherin transcriptional regulators in ovarian carcinoma.
AB  - Unlike most epithelial cancers, E-cadherin expression is upregulated in ovarian
      carcinoma effusions compared with corresponding primary tumors. In the present
      study, we analyzed the anatomic site-specific expression of transcription factors
      that negatively regulate E-cadherin in ovarian carcinoma. Using reverse
      transcription polymerase chain reaction, mRNA in situ hybridization, and Western
      blotting, we analyzed the expression and localization of the Snail, Slug, and
      SIP1 transcription factors and E-cadherin in 78 effusions, 41 primary carcinomas,
      and 15 solid metastases. Slug mRNA and protein expression was highest in
      metastases (p=0.042 and p<0.001, respectively). Snail mRNA was comparable at all
      anatomic sites, but higher protein expression was found in primary tumors and
      solid metastases compared with effusions (p<0.001). SIP1 mRNA expression was
      higher in effusions (p<0.001) compared to other sites. Confocal microscopy
      analysis of fresh and cultured cells from effusion specimens revealed cytoplasmic
      localization of the Snail protein in primary tumor cells, with a nuclear shift
      following culturing of these cells. In conclusion, E-cadherin and its negative
      regulators show site-dependent expression in ovarian carcinoma. In solid tumors,
      E-cadherin is negatively regulated by Snail and Slug. In effusions, SIP1 may be
      the main regulator of E-cadherin, but with a lesser level of suppression compared
      with primary tumors and solid metastases.

PMID- 17024426
TI  - Effect of organic solvents on the activity and stability of an extracellular
      protease secreted by the haloalkaliphilic archaeon Natrialba magadii.
AB  - The effect of various organic solvents on the activity and stability of an
      extracellular protease produced by the haloalkaliphilic archaeon Natrialba
      magadii was tested. This protease was active and stable in aqueous-organic
      solvent mixtures containing 1.5 M NaCl and glycerol, dimethylsulfoxide (DMSO),
      N,N-dimethyl formamide, propylenglycol, and dioxane. Among the solvents tested,
      DMSO, propylenglycol, and glycerol were effective in preserving enzyme stability
      in suboptimal NaCl concentrations. The stabilizing effect of DMSO on this
      haloalkaliphilic protease was more efficient at pH 8 than at pH 10, suggesting
      that DMSO may not substitute for salt to allow halophilic proteins to withstand
      the effect of high pH values. These results show that Nab. magadii extracellular
      protease is a solvent tolerant enzyme and suggest a potential application of this
      haloalkaliphilic protease in aqueous-organic solvent biocatalysis.

PMID- 17024427
TI  - Complex gene-gene interactions in multiple sclerosis: a multifactorial approach
      reveals associations with inflammatory genes.
AB  - The complex inheritance involved in multiple sclerosis (MS) risk has been
      extensively investigated, but our understanding of MS genetics remains
      rudimentary. In this study, we explore 51 single nucleotide polymorphisms (SNPs)
      in 36 candidate genes from the inflammatory pathway and test for gene-gene
      interactions using complementary case-control, discordant sibling pair, and trio
      family study designs. We used a sample of 421 carefully diagnosed MS cases and 96
      unrelated, healthy controls; discordant sibling pairs from 146 multiplex
      families; and 275 trio families. We used multifactor dimensionality reduction to
      explore gene-gene interactions. Based on our analyses, we have identified several
      statistically significant models including both main effect models and two-locus,
      three-locus, and four-locus epistasis models that predict MS disease risk with
      between approximately 61% and 85% accuracy. These results suggest that
      significant epistasis, or gene-gene interactions, may exist even in the absence
      of statistically significant individual main effects.

PMID- 17024429
TI  - Proactive interference in a two-tone pitch-comparison task without additional
      interfering tones.
AB  - Two-tone pitch-comparison tasks typically comprise several successive pairs of
      successive tones separated by silent intervals. The serial occurrence of such
      pairs has been associated with degraded task performance, but the nature of this
      association is not fully understood. Human adult participants were presented with
      successive pairs of successive tones. The latter, to-be-compared tone of a pair
      could differ from the former, to-be-remembered tone of 1046.5 Hz by no more than
      +/-15 Hz (25 cents). The direction of this difference was easier to identify when
      it was opposite to that of the preceding pair than when being the same. Merely
      responding accordingly (irrespectively of whether the response was correct or
      not) was found not to account for this finding. Our study demonstrates proactive
      interference in a two-tone pitch comparison task as the difficulty to remember
      when the first tone of the present pair occurred relative to the last tone of the
      immediately preceding pair.

PMID- 17024428
TI  - Genomic analysis of the rhg1 locus: candidate genes that underlie soybean
      resistance to the cyst nematode.
AB  - The rhg1 gene or genes lie at a recessive or co-dominant locus, necessary for
      resistance to all Hg types of the soybean (Glycine max (L.) Merr.) cyst nematode
      (Heterodera glycines I.). The aim here was to identify nucleotide changes within
      a candidate gene found at the rhg1 locus that were capable of altering resistance
      to Hg types 0 (race 3). A 1.5 +/- 0.25 cM region of chromosome 18 (linkage group
      G) was shown to encompass rhg1 using recombination events from four near isogenic
      line populations and nine DNA markers. The DNA markers anchored two bacterial
      artificial chromosome (BAC) clones 21d9 and 73p6. A single receptor like kinase
      (RLK; leucine rich repeat-transmembrane-protein kinase) candidate resistance gene
      was amplified from both BACs using redundant primers. The DNA sequence showed
      nine alleles of the RLK at Rhg1 in the soybean germplasm. Markers designed to
      detect alleles showed perfect association between allele 1 and resistance to
      soybean cyst nematode Hg types 0 in three segregating populations, fifteen
      additional selected recombination events and twenty-two Plant Introductions. A
      quantitative trait nucleotide (QTN) [corrected] in the RLK at rhg1 was inferred
      that alters A87 to V87 in the context of H274 rather than N274. [corrected]
      Contiguous DNA sequence of 315 kbp of chromosome 18 (about 2 cM) contained
      additional gene candidates that may modulate resistance to other Hg-types
      including a variant laccase, a hydrogen-sodium ion antiport and two proteins of
      unknown function. A molecular basis for recessive and co-dominant resistance that
      involves interactions among paralagous disease-resistance genes was inferred that
      would improve methods for developing new nematode-resistant soybean cultivars.

PMID- 17024431
TI  - Spatial updating in virtual reality: the sufficiency of visual information.
AB  - Robust and effortless spatial orientation critically relies on "automatic and
      obligatory spatial updating", a largely automatized and reflex-like process that
      transforms our mental egocentric representation of the immediate surroundings
      during ego-motions. A rapid pointing paradigm was used to assess
      automatic/obligatory spatial updating after visually displayed upright rotations
      with or without concomitant physical rotations using a motion platform. Visual
      stimuli displaying a natural, subject-known scene proved sufficient for enabling
      automatic and obligatory spatial updating, irrespective of concurrent physical
      motions. This challenges the prevailing notion that visual cues alone are
      insufficient for enabling such spatial updating of rotations, and that
      vestibular/proprioceptive cues are both required and sufficient. Displaying optic
      flow devoid of landmarks during the motion and pointing phase was insufficient
      for enabling automatic spatial updating, but could not be entirely ignored
      either. Interestingly, additional physical motion cues hardly improved
      performance, and were insufficient for affording automatic spatial updating. The
      results are discussed in the context of the mental transformation hypothesis and
      the sensorimotor interference hypothesis, which associates difficulties in
      imagined perspective switches to interference between the sensorimotor and
      cognitive (to-be-imagined) perspective.

PMID- 17024430
TI  - Does attention impair temporal discrimination? Examining non-attentional
      accounts.
AB  - Recently, Yeshurun and Levy (Psychol Sci 14:225-231, 2003) have provided evidence
      for the notion that visual attention impairs the temporal resolution of the
      visual system. Specifically, the detection of a temporal gap within a visual
      stimulus was impaired when a cue directed attention towards the spatial location
      of the stimulus. As this negative cueing effect is important to constrain
      theories about visual attention, we further investigated this novel effect and
      assessed whether it truly reflects an attentional effect. Experiment 1 examines
      whether the negative cueing effect is due to local temporal interference, and
      Experiments 2 and 3 investigate whether it reflects a luminance confound. The
      complete pattern of results argues against these alternatives and thus further
      strengthens the conclusion of Yeshurun and Levy (Psychol Sci 14: 225-231, 2003).

PMID- 17024432
TI  - Muscarinic cholinoceptor-stimulated phosphatidyl inositol pathway in corneal
      epithelial and endothelial cells.
AB  - BACKGROUND: Muscarinic cholinoceptors are distributed widely in both the central
      and peripheral nervous system. The presence of muscarinic cholinoceptors in
      corneal tissue is well established. Previous reports have shown that corneal
      muscarinic cholinoceptors are of the m2 or m4 subtype. However, recent studies
      have indicated the presence of the m5 muscarinic cholinoceptor subtype in human
      corneal epithelium and endothelium. The aim of the study was to confirm the
      presence of the m5 cholinoceptor subtype in bovine corneal epithelium and
      endothelium and the activation of phosphatidyl inositol pathway by its
      stimulation. METHODS: Muscarinic m5 cholinoceptor sites, phosphatidyl inositol
      4,5-biphosphate, inositol 1,4,5-triphosphate and protein kinase C, were studied
      using immunocytochemistry and immunofluorescence. Activation of protein kinase C
      after stimulation of the m5 muscarinic cholinoceptor subtype was measured using
      the HTS protein kinase C assay kit. RESULTS:
      Immunocytochemistry/immunofluorescence revealed the presence of the m5 muscarinic
      cholinoceptor subtype, phosphatidyl inositol 4,5-biphosphate and protein kinase C
      in bovine corneal epithelial and endothelial cells. In bovine corneal epithelium
      and endothelium, protein kinase C activity was stimulated by acetylcholine in a
      dose-dependent manner (P<0.0001). CONCLUSIONS: Our findings indicate that
      acetylcholine-induced stimulation of muscarinic m5 cholinoceptors activates the
      phosphatidyl inositol pathway in corneal epithelial and endothelial cells,
      resulting in increased protein kinase C activity. Further work will be needed to
      clear the physiologic role of this signaling pathway in corneal epithelium and
      endothelium.

PMID- 17024434
TI  - Confocal microscopy imaging of the cornea in patients with silicone oil in the
      anterior chamber after vitreoretinal surgery.
AB  - OBJECTIVE: Evaluation of corneal morphology by confocal microscopy after
      vitreoretinal surgery complicated by passage of silicone oil into the anterior
      chamber. Design Case series (case control study). METHODS: Eight patients (eight
      eyes) who had undergone vitreoretinal surgery and had silicone oil in the
      anterior chamber but no clinically evident corneal abnormalities made up the
      patient group. The control group consisted of eight patients (eight eyes) who had
      undergone vitreoretinal surgery with application of silicone oil tamponade but
      who had no silicone oil clinically observable in the anterior chamber. In vivo
      examination of the cornea using a ConfoScan 3 (Nidek Technologies) confocal
      microscope equipped with the standard 40x immersion lens was performed. Central,
      upper, and lower parts of the cornea were assessed separately. High-magnification
      evaluation of the status of corneal layers and endothelial cell density in upper
      parts of the cornea directly in contact with silicone oil in the anterior chamber
      and in parts of the cornea not in direct contact with silicone oil was carried
      out. RESULTS: Alterations in corneal morphology, especially in endothelium and
      posterior and medium stroma, were observed. In all cases, changes were more
      advanced in the upper part of the cornea. Endothelial cell density was
      significantly decreased in upper parts of the cornea. CONCLUSIONS: In patients
      with silicone oil in the anterior chamber, confocal microscopy imaging reveals
      early morphological alterations of the cornea before their clinical
      manifestation.

PMID- 17024435
TI  - Macular hole surgery complicated by accidental massive subretinal indocyanine
      green, and retinal tear.
AB  - BACKGROUND: To report a case of macular hole (MH) surgery complicated by
      accidental massive subretinal indocyanine green (ICG), and a retinal tear through
      the papillomacular bundle. METHODS: A 64-year-old woman complained of one-year
      history of poor vision in her left eye (LE) and of one month in her right (RE).
      Dilated fundus examination, fluorescein angiography, and optical coherence
      tomography (OCT) demonstrated a bilateral full-thickness MH with cystic changes
      and no posterior vitreous detachment RE and a full-thickness hole with
      significant surrounding retinal edema and cystic changes LE. RESULTS: A
      vitrectomy and posterior vitreous mechanical detachment were performed to close
      the MH RE. Approximately 0.3 ml of 0.5% ICG was applied to stain the internal
      limiting membrane (ILM). The assistant surgical nurse at the beginning of the
      instillation pushed the ICG syringe's embolus with too much force into the
      vitreous cavity with a 20-gauge cannula. Subretinal ICG was accidentally
      introduced through the macular hole, and an iatrogenic macular retinal tear
      though the papillomacular bundle was created. Infusion was resumed immediately,
      and ICG was removed from the vitreous cavity, and the ILM was removed in a
      circular fashion in the usual manner. The eye was left with 14% perfluoropropane
      gas. Fundus examination and OCT performed after the intraocular gas was
      reabsorbed one month after the surgery revealed that the macular hole was
      completely closed with choroidal hypereflectivity due to RPE and choriocapillaris
      atrophy. Best-corrected visual acuity was 20/150 with a closed macular hole and
      ICG still present in the subretinal space seven months after surgery. CONCLUSION:
      Our anatomic and functional results were poor with retinal and retinal pigment
      epithelium (RPE) atrophy, and a visual acuity of 20/150. Subretinal ICG and
      contact of ICG with the RPE should be avoided, and precautions should be taken
      when using intravitreous ICG to stain the ILM. Further studies are necessary to
      determine ICG safety in vitreoretinal surgery.

PMID- 17024436
TI  - Asymmetric dimethylarginine is not elevated in exfoliation syndrome but symmetric
      dimethylarginine is related to exfoliative glaucoma.
AB  - BACKGROUND: Hyperhomocysteinemia (HH), oxidative stress and endothelial
      dysfunction are all implicated as possible pathogenetic factors in exfoliation
      syndrome (XFS) and exfoliative glaucoma (XFG). Asymmetric dimethylarginine (ADMA)
      is an endogenous inhibitor of endothelial nitric oxide and plasma level of ADMA
      is often elevated in HH. Thus the present study was undertaken to study plasma
      levels of ADMA with concomitant measurement of symmetric dimethylarginine (SDMA)
      and L-arginine (L-Arg) in XFS and XFG. METHODS: This cross-sectional, prospective
      study involved 36 XFS patients, 11 of them having XFG, and 36 age- and gender
      matched controls. Fasting plasma ADMA, SDMA and L-Arg levels of participants were
      determined. A special view was created how plasma L-Arg, ADMA and SDMA correlate
      to plasma homocysteine (P-Hcy). In addition, the influence of P-Hey values
      derived from our previous study on the above mentioned parameters were evaluated
      by cut-off values of P-Hcy, 12 micromol/l for women and 14.5 micromol/l for men.
      RESULTS The mean plasma ADMA, SDMA and L-Arg levels were 0.41, 0.49 and 62.9
      micromol/l in the XFS/XFG group, and 0.41, 0.44 and 69.7 micromol/l in the
      control group, respectively. As all parameters within the XFS and control group
      were compared, no statistical significance was stated. On the other hand, a
      positive correlation was observed between plasma SDMA and P-Hcy in XFGs (P =
      0.002), and additionally, also a statistically significant difference was in
      plasma SDMA between the two groups sorted by cut-off levels of P-Hcy 0.49 +/-
      0.15 vs. 0.36 +/- 0.04 micromol/l, above and below cut-off levels, respectively
      (P = 0.001), but not between ADMA in a respective assay. The mean values of L-Arg
      were 64.6 +/- 17.2 vs. 74.8 +/- 13.3 microg/l, respectively (P = 0.031). In the
      XFS subgroup, on the contrary, there was no positive correlation between P-Hcy
      and plasma SDMA. CONCLUSIONS: A positive correlation of plasma SDMA in respect to
      P-Hcy in XFGs and increase of SDMA in mild or intermediate hyperhomocysteinemia
      may indicate SDMA as a marker of developing XFG in hyperhomocysteinemic

PMID- 17024437
TI  - Nonarteritic anterior ischemic optic neuropathy and 'visual field defects'
      following vitrectomy: could they be related?
AB  - BACKGROUND: Visual field defects after uncomplicated vitrectomy have been
      reported but poorly explained. We describe two cases of nonarteritic anterior
      ischemic optic neuropathy (NAION) observed following vitrectomy. We also reviewed
      the literature for cases of post-vitrectomy visual field defects for evidence of
      optic nerve damage. METHODS: Two patients developed optic disc edema and features
      of an optic neuropathy after uncomplicated vitrectomy for macular hole and
      epiretinal membrane. A systematic literature search was conducted to obtain prior
      reports of visual field defects or ischemic optic neuropathy following
      vitrectomy. Additional studies were identified from the bibliographies of the
      retrieved articles. RESULTS: The incidence of visual field defects following
      vitrectomy has varied from 1-71% across all studies. Overall, we found 160
      (14.5%) cases of unexplained visual field defects following vitrectomy out of
      1,104 patients. Of these, 31 eyes (19.4%) have shown some sign of optic nerve
      damage following vitrectomy, including pallor in 29 eyes, relative afferent
      pupillary defect in eight eyes, and intrapapillary hemorrhage in two eyes.
      CONCLUSIONS: NAION may develop following vitrectomy. "Visual field defects"
      following vitrectomy are common and many of the involved eyes demonstrate
      evidence of optic nerve damage, some of which may have represented NAION.

PMID- 17024438
TI  - Magnification-corrected photodynamic therapy.
AB  - BACKGROUND: To present a method for performing photodynamic therapy (PDT) with a
      constant predictable light fluence based on actual laser spot magnification.
      METHODS: A calibrated Gullstrand-type model eye with a scale of half circles in
      the centre of the artificial fundus was used for this study. The axial length of
      the model eye was set to different values ranging from 20 to 31 mm, and the
      actual laser spot magnification of four indirect condensing laser lenses were
      determined using a PDT laser unit. RESULTS: Equations for determining the actual
      laser spot magnification were calculated for each laser lens. The total change in
      laser spot magnification from hyperopia (axial length 20 mm) to myopia (axial
      length 31 mm) was -20% to +24.8% for Mainster Standard lens (Ocular Instruments
      Inc, Bellevue, Washington, USA), -15.7% to +27.7% for Mainster Wide Field lens
      (Ocular Instruments Inc), -16.3% to +33.1% for Volk Transequator lens (Volk
      Optical Inc, Mentor, Ohio, USA), and -19.2% to +24.4% for Volk PDT Laser lens
      (Volk Optical Inc). CONCLUSIONS: Axial length of the eye has a considerable
      effect on PDT laser spot magnification when an indirect laser lens is used. By
      calculating the actual laser spot magnification in conjunction with knowledge of
      the true greatest linear dimension of the neovascular lesion, the clinician may
      be able to deliver a constant predictable amount of light fluence to the fundus
      independent of the axial length of the PDT treating eye.

PMID- 17024439
TI  - Clear graft survival and immune reactions following emergency keratoplasty.
AB  - BACKGROUND: Emergency penetrating keratoplasty is said to have a poorer outcome
      than conventional keratoplasty. We performed a retrospective analysis of 272
      cases of emergency keratoplasty to evaluate this hypothesis. METHODS: We analysed
      272 cases of emergency keratoplasty and compared the results with a control group
      of 1,257 scheduled normal-risk keratoplasties and 407 scheduled high-risk
      keratoplasties. Kaplan-Meier estimations were performed to estimate the
      percentage of clear graft survival and development of immune reactions.
      Indications for emergency keratoplasty were microbial diseases (n=109,
      acanthamoeba, bacteria, fungi), herpes simplex virus infections (n=83), ulcers
      due to immunological diseases (n=63), and 17 cases of ulcers of unknown origin.
      RESULTS: Within 1,500 postoperative days, grafts following emergency keratoplasty
      suffered statistically significantly more graft failures (clear graft survival,
      67.9 vs. 86.9%, P<0.01) and immune reactions (grafts free from immune reactions,
      62.8 vs. 78.6%, P<0.01) than grafts following scheduled, normal-risk
      keratoplasty. There was no statistically significant difference between emergency
      and scheduled high-risk keratoplasties (clear graft survival, 67.9 vs. 70.2%, and
      grafts free from immune reactions, 62.8 vs. 66.8%). For emergency keratoplasties,
      systemic immunosuppression (with cyclosporin A and/or mycophenolatmophetil) had a
      statistically significant positive effect on clear graft survival (77.4 vs.
      63.5%, P=0.01), but not on the development of immune reactions (62.8 vs. 62.3%).
      A sub-group analysis showed that the effect on clear graft survival was mainly an
      effect on the underlying systemic immunological disease that had lead to
      emergency keratoplasty. CONCLUSION: This retrospective analysis revealed that
      clear graft survival is limited following emergency keratoplasty. As in high-risk
      situations, systemic immunosuppression may be the key to improving prognosis
      following emergency keratoplasty in the long run.

PMID- 17024440
TI  - Roles of CD4+CD25+ T cells in the development of experimental murine allergic
      conjunctivitis.
AB  - BACKGROUND: CD25+ regulatory T (T reg) cells play a suppressive role in
      experimental autoimmune uveoretinitis as well as experimental airway inflammation
      but their involvement in the development of allergic conjunctivitis (AC) remains
      unclear. We therefore investigated whether T reg cells play a role in the
      development of experimental AC (EC). METHODS: BALB/c and C57BL/6 mice were
      actively immunized with ragweed (RW). The mice were treated with an anti-CD25 Ab
      (PC61) or control normal rat IgG (nrIgG) either 2 days prior to active
      immunization or during the induction phase (days 0, 2, 4, 6 and 8). Ten days
      after active immunization, the mice were challenged with RW-containing drops.
      Twenty-four hours after the challenge, the conjunctivas were harvested for
      histological analysis of eosinophil infiltration, and the spleens were harvested
      for cell culture for splenocyte transfer. Cultured splenocytes were transferred
      into syngeneic mice, and 4 days after the transfer, the recipient mice were
      challenged with RW. Twenty-four hours after the challenge, conjunctivas were
      collected for histological analysis. RESULTS: Pretreatment with PC61 did not
      affect EC in either strain of mice; however, treatment with PC61 during the
      induction phase significantly suppressed EC in C57BL/6 mice. In contrast,
      transfer of RW-primed splenocytes from mice treated with PC61 induced EC that was
      significantly more severe regardless of strain and treatment protocol.
      CONCLUSIONS: The finding that T reg cells play a suppressive role in the
      development of EC in splenocyte transfer experiments suggests that modulation of
      T reg cells may be a possible therapy for AC.

PMID- 17024441
TI  - Scleral window surgery and topical mitomycin C for nanophthalmic uveal effusion
      complicated by renal failure: case report.
AB  - PURPOSE: To describe the case of a 16-year-old patient with nanophthalmic uveal
      effusion associated with renal failure that was treated with scleral window
      surgery and topical administration of mitomycin C (MMC). METHODS: Case report.
      RESULTS: Total uveal effusion was restored in the nanophthalmic eyes. Partial
      thickness scleral flap with deep sclerostomy was performed and topical MMC was
      administered to one quadrant of the equatorial sclera. The subretinal fluid
      resorbed gradually. CONCLUSIONS: Topical MMC might relieve the blocked
      transscleral outflow of intraocular fluid in the small area of a sclerostomy in
      young patients with nanophthalmos or in patients with renal failure in whom uveal
      effusion occurs repeatedly.

PMID- 17024442
TI  - The involvement of matrix metalloproteinases 2 and 9 in rat retinal ischemia.
AB  - BACKGROUND: The involvement of matrix metalloproteinases (MMPs) in ischemic
      tissue damage and remodeling has been reported by many investigators. Our study
      was designed to investigate the involvement of MMPs and of tissue inhibitors of
      metalloproteinases (TIMPs) in rat retinal ischemic injury, the effect of nitric
      oxide synthase (NOS) inhibitors on MMPs' activity in this model and whether
      minocycline (an MMP inhibitor) is protective in retinal ischemia. METHODS: Ninety
      four rats were used in the study. Ischemia was induced by 90 min elevation of
      intraocular pressure. MMPs' activities and the effect of NOS inhibitors
      [aminoguanidine (AG) or N-nitro-L-arginine (NNA)] and minocycline on MMPs'
      activities were assessed by zymography and TIMPs expression by Western analysis.
      Morphological damage was quantified by morphometry of hematoxylin and eosin
      stained retinal sections. RESULTS: Retinal extracts exhibited activities of
      proMMP-9 and proMMP-2. The activity of proMMP-9 increased immediately post
      ischemia (PI) and peaked to 4.6 times that of normal untreated controls in
      ischemic retinas and to 2.6 times that of controls in retinas of fellow sham
      treated eyes at 24 h PI. The relative amount of TIMP-1 increased to 1.9-fold
      following ischemia and 2.5-fold in fellow sham-treated eyes at 24 h PI. ProMMP-2
      activity increased more than two-fold immediately, at 24 h and at 48 h PI in
      ischemic retinas, and insignificantly in fellow sham-treated eyes. Treatment with
      25 mg/kg AG or NNA caused a non-significant increase in proMMP-9 activity at 24 h
      PI (3.7- and 2.9-fold, respectively, p>0.6). There was no effect of AG or NNA on
      the activity of proMMP-2. Minocycline significantly attenuated the retinal
      ischemic damage, primarily by partially preserving ganglion cells and the inner
      plexiform layer. Minocyline (0.5 mg/ml or 5 mg/ml) inhibited MMPs' activities in
      ischemic retinal extracts in vitro. CONCLUSIONS: MMPs participated in
      morphological ischemic damage to rat retina. Treatment with minocycline
      dramatically attenuated damage to the retina.

PMID- 17024443
TI  - [Diagnosis of supranuclear eye movement disorders. Part II: Vertical and
      torsional oculomotoricity].
AB  - The hallmark of a supranuclear eye movement disorder is functional impairment of
      one or several types of different eye movements while other types of eye movement
      remain unchanged. All eye movement information is conveyed via the nuclei of the
      eye muscle nerves. However, the information for a specific type of eye movement
      is generated in prenuclear cortical and subcortical areas which are activated
      depending on the type of eye movement performed. The structures responsible for
      vertical and torsional oculomotoricity are described as well as the functional
      relationship between them. A summary of the development of saccades and movements
      arising from them is also given and the influence of the cerebellum on oculomotor
      processes is dealt with. In many neurological conditions knowledge about the
      areas of the brain relevant for eye movement enables a clinical diagnosis to be
      made or the pathological process to be localized to a specific anatomical area.
      Examination of eye movements is thus a valuable clinical tool in many
      neurological and neuro-ophthalmological diseases.

PMID- 17024445
TI  - [Investigations on the Armed Forces Institute of pathology, Washington D. C, A
      practical report].

PMID- 17024444
TI  - [Wear particles: key to aseptic prosthetic loosening?].
AB  - The aseptic prosthetic loosening of hip and knee prosthesis is the most important
      cause of implant insufficiency. Bone loss as a result of the biological effect of
      wear particles is the main cause of such loosening. Wear particles develop their
      biological activity along different cellular pathways, above all via macrophages,
      foreign body giant cells as well as fibroblasts of the periprosthetic membrane.
      These cells induce particle-dependent bone resorption by means of proinflammatory
      cytokines, such as IL-1beta, TNF-alpha, IL-6 and PGE2. These factors induce the
      activation of osteoclasts as well as the suppression of osteoblasts. Neutrophil
      granulocytes and lymphocytes do not play an important role in the process of
      aseptic loosening. The different wear particles, such as ultra-high molecular
      weight polyethylene, metal particles, ceramic particles and
      polymethylmethacrylate can be morphologically recognized very easily. From the
      clinical point of view, the differentiation between acute or chronic implant
      infection and particle induced prosthetic loosening is very important, with the
      histomorphological differential diagnosis between septic and aseptic loosening
      and their combination being the key clinicopathological factor.

PMID- 17024447
TI  - Zinc finger protein 1 (ThZF1) from salt cress (Thellungiella halophila) is a Cys
      2/His-2-type transcription factor involved in drought and salt stress.
AB  - Zinc finger proteins (ZFPs) play important roles in growth and development in
      both animals and plants. Recently, some Arabidopsis genes encoding distinct ZFPs
      have been identified. However, the physiological role of their homologues with
      putative zinc finger motif remains unclear. In the present study, a novel gene,
      ThZF1, was characterized from salt stressed cress (Thellungiella halophila, Shan
      Dong), encoding a functional transcription factor. ThZF1 contains two conserved
      C(2)H(2) regions and shares conserved domains, including DNA-binding motif, with
      Arabidopsis thaliana ZFP family members. The transcript of the ThZF1 gene was
      induced by salinity and drought. Transient expression analysis of ThZF1-GFP
      fusion protein revealed that ThZF1 was localized preferentially in nucleus. A gel
      shift assay showed that ThZF1 specially bind to the wild-type (WT) EP2 element, a
      cis-element present in the promoter regions of several target genes regulated by
      ZFPs. Furthermore, a functional analysis demonstrated that ThZF1 was able to
      activate HIS marker gene in yeast. Finally, ectopic expression of ThZF1 in
      Arabidopsis mutant azf2 suggested that ThZF1 may have similar roles as
      Arabidopsis AZF2 in plant development as well as regulation of downstream gene.

PMID- 17024448
TI  - Delayed flowering time in Arabidopsis and Brassica rapa by the overexpression of
      FLOWERING LOCUS C (FLC) homologs isolated from Chinese cabbage (Brassica rapa L.:
      ssp. pekinensis).
AB  - Chinese cabbage plants remain in the vegetative growth phase until they have
      experienced prolonged exposure to cold temperature, known as vernalization. This
      inhibition of flowering is caused by the high levels of FLOWERING LOCUS C (FLC)
      expression. To increase the product value of Chinese cabbage by inhibiting the
      floral transition, three genes (BrFLC1, BrFLC2, and BrFLC3) homologous to the
      AtFLC gene, which encodes a floral repressor, were isolated from the Chinese
      cabbage 'Chiifu'. These genes showed high similarity to AtFLC, although the
      putative BrFLC1 protein contained ten more residues than AtFLC. The BrFLC genes
      were expressed ubiquitously, except that BrFLC3 was not expressed in roots.
      BrFLC1 and BrFLC2 showed stronger expression than BrFLC3 in unvernalized and
      vernalized Chinese cabbage. The expression levels of the three BrFLC genes were
      lower in an early-flowering Chinese cabbage, suggesting that the BrFLC transcript
      level was associated with flowering time. Constitutive expression of the BrFLC
      genes in Arabidopsis significantly delayed flowering, which was also observed in
      transgenic Chinese cabbage overexpressing BrFLC3. These results suggest that the
      BrFLC genes act similarly to AtFLC. Our results provide a technique for
      controlling flowering time in Chinese cabbage and other crops to produce high
      yields of vegetative tissues.

PMID- 17024449
TI  - High frequency early in vitro flowering of Dendrobium Madame Thong-In
      (Orchidaceae).
AB  - We have successfully developed a method to induce early in vitro flowering of the
      self-pollinated seedlings of a tropical orchid hybrid, Dendrobium Madame Thong
      In. Transition of vegetative shoot apical meristem to inflorescence meristem was
      observed when young protocorms were cultured in modified KC liquid medium. In
      contrast, protocorms cultured on Gelrite-solidified medium only produced axillary
      shoots and roots. CW was required to trigger the transitional shoot apical
      meristem and BA enhanced inflorescence stalk initiation and flower bud formation.
      However, normal flower development was deformed in liquid medium but developed
      fully upon transferring to two-layered (liquid over Gelrite-solidified) medium.
      Under optimal condition, in vitro flowering was observed about 5 months after
      seed sowing. Segregation of flower colours was observed in these seedlings and
      seedpods formed upon artificial pollination of the in vitro flowers.

PMID- 17024450
TI  - Expression analysis of the gastrodianin gene ga4B in an achlorophyllous plant
      Gastrodia elata Bl.
AB  - Gastrodia elata Bl. is an achlorophyllous orchid plant feeding on the fungus
      Armillaria mellea. The plant lives underground during its life cycle except for
      florescence. Gastrodianins, members of the superfamily of monocot mannose-binding
      protein (MBP), have been identified from Gastrodia elata, yet their physiological
      functions in the plant are rarely understood. Aspects of expression of
      gastrodianins in growth and development of the plant will be helpful to dissect
      their functional roles. Two types of cDNA clones with complete cDNA sequences
      matching the known gastrodianins were obtained from G. elata Bl.f.glauca S.chow
      (Orchidaceae) and designated gastrodianin-4A (ga4A) and gastrodianin-4B (ga4B),
      respectively. But only one isoform was found to be expressed in all different
      parts of a single plant. Based on the RNA gel blot analysis, gastrodianins were
      much more abundantly expressed in the fully opened flowers than the underground
      corms where an enhanced expression was found in the out layers of secondary
      corms. By RNA in situ hybridization gastrodianin transcripts were distinctly
      detected in the cortical cells and vascular cells of corms. Strong transcript
      accumulations were observed in two to eight layers of cortical cells in secondary
      corms. From its peripheral tissue expression pattern and level in corms and
      flowers, the gastrodianin may account for a possible defense against
      phytopathogens or insects.

PMID- 17024451
TI  - Transformation and segregation of GFP fluorescence and glyphosate resistance in
      horseweed (Conyza canadensis) hybrids.
AB  - The goal of this research was to generate a breeding population of horseweed
      segregating for glyphosate resistance. In order to generate a marker to select
      between hybrids of glyphosate resistant (GR) and glyphosate susceptible (GS)
      horseweed, a GR horseweed accession from western Tennessee was transformed with a
      green fluorescent protein (GFP) transgene. The GFP marker allowed for the simple
      and accurate determination of GR hybrid plants by visual observation. GR plants
      were shown to be transgenic via the green fluorescence under UV light, and
      resistant to glyphosate when sprayed with the field-use-rate 0.84 kg acid
      equivalent ha(-1) of glyphosate (i.e. Roundup) herbicide. An in vitro screen for
      glyphosate resistance in seedlings was developed, and a 5 microM glyphosate
      concentration was found to reduce dry weight in GS seedlings but not in GR
      seedlings. The GR plants containing GFP were then hand-crossed with GS plants
      from eastern Tennessee under greenhouse conditions, with GS plants acting as the
      pollen acceptor. Resulting seed was collected and germinated for GFP fluorescence
      screening. Seedlings that exhibited the transgenic GFP phenotype were selected as
      F(1) hybrids between GR and GS horseweed. Thirty GSxGR hybrids were produced on
      the basis of a green-fluorescent GFP phenotype of GR plants. GSxGFP/GR F(1)
      hybrids produced F(2) seeds, and F(2) plants were shown to segregate for GFP
      fluorescence and glyphosate resistance independently. Both traits segregated at a
      Mendelian 3:1 ratio, indicating a single gene is responsible for each phenotype.

PMID- 17024452
TI  - Expression of an Arabidopsis CAX2 variant in potato tubers increases calcium
      levels with no accumulation of manganese.
AB  - Previously, we made a chimeric Arabidopsis thaliana vacuolar transporter CAX2B [a
      variant of N-terminus truncated form of CAX2 (sCAX2) containing the "B" domain
      from CAX1] that has enhanced calcium (Ca(2+)) substrate specificity and lost the
      manganese (Mn(2+)) transport capability of sCAX2. Here, we demonstrate that
      potato (Solanum tuberosum L.) tubers expressing the CAX2B contain 50-65% more
      calcium (Ca(2+)) than wild-type tubers. Moreover, expression of CAX2B in potatoes
      did not show any significant increase of the four metals tested, particularly
      manganese (Mn(2+)). The CAX2B-expressing potatoes have normally undergone the
      tuber/plant/tuber cycle for three generations; the trait appeared stable through
      the successive generations and showed no deleterious alternations on plant growth
      and development. These results demonstrate the enhanced substrate specificity of
      CAX2B in potato. Therefore, CAX2B can be a valuable tool for Ca(2+) nutrient
      enrichment of potatoes with reduced accumulation of undesirable metals.

PMID- 17024453
TI  - The 20-min trial of the maintenance of wakefulness test is profoundly affected by
      motivation.
AB  - Assessment of the ability to maintain wakefulness, although very important both
      for research and for clinical purposes, is still equivocal. The current gold
      standard is considered the Maintenance of Wakefulness Test (MWT), although there
      are two different potential protocols to perform it and the normal reference
      range has been determined on selected populations. The effect of potential
      "penalty" on failing the test (i.e., presenting sleepiness) has not been
      seriously studied. We therefore planned this study to examine the effect of
      motivation on the MWT results in a potentially sleepy population. We hypothesized
      that with the knowledge that participants may lose their driving license if they
      fail the test, the results would indicate significantly less sleepiness than
      reported for other populations. Fifty-four consecutive subjects at high risk of
      sleepiness referred to the sleep laboratory for evaluation of their ability to
      maintain wakefulness were studied. All were referred by the National Council for
      Driving Safety, knowing that if they failed the test, their driving license would
      not be renewed. Referral reasons were previously diagnosed: obstructive sleep
      apnea (OSA; 43%), sleep-related accident (7%), or other causes to suspect
      sleepiness. All underwent a full-night polysomnography (PSG) followed by MWT,
      five trials of 20 min each (MWT20). Of the 54 participants, 13 were treated for
      OSA and 28 had untreated OSA, 21 of them had severe OSA (Respiratory Disturbance
      Index > 30/h). Seventy-four percent of the participants had a BMI >30 kg/m2. Only
      5 of the participants fell asleep in any of the MWT trials (one to five trials),
      which could not be predicted by severity of OSA, age, BMI, or variables derived
      from the previous night PSG. Of the 21 patients with severe untreated OSA, only 1
      patient fell asleep during the MWT20. We conclude that motivation profoundly
      affects the MWT results, raising the question what should be considered normal or
      abnormal when sleepy results may cause penalty or other practical implications.
      In addition, we believe that these results suggest that for renewal of driving
      license purposes, the MWT20 is insufficient. We speculate that MWT40, with
      tighter cutoff threshold, would be a more effective tool.

PMID- 17024454
TI  - DNAse I pre-treatment markedly enhances detection of nuclear cyclin-dependent
      kinase inhibitor p57Kip2 and BrdU double immunostaining in embryonic rat brain.
AB  - As a member of the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs),
      p57Kip2 binds tightly to G1 cyclin/cyclin-dependent kinase complexes to block
      cell cycle progression. CKIs play critical roles in regulating the transition
      from proliferation to differentiation in many tissues, including the nervous
      system. Conversely, CKI dys-regulation contributes to neoplasia and cancer
      progression. While the combined detection of CKI immunoreactivity and S phase
      entry using bromodeoxyuridine (BrdU) incorporation may be particularly
      informative, successful immunostaining may be limited due to "masked" antigen
      epitopes and acid-induced signal degradation. We now report an improved double
      immunofluorescent method for detecting p57Kip2 and BrdU in paraformaldehyde-fixed
      frozen sections of embryonic rat brain. We substituted deoxyribonuclease I (DNAse
      I) for HCl pre-treatment to expose antigenic sites in frozen sections, and
      employed a biotinylated tyramide-based system to enhance p57Kip2 visualization.
      We identified a time- and dose-dependent relationship between DNAse I treatment
      and double labeling of p57Kip2 and BrdU, increasing both the numbers and
      intensities of immunopositive nuclei. With excess DNAse I treatment, however,
      there was signal degradation for both BrdU and total DNA, as reflected by DAPI
      staining. The use of DNAse I pre-treatment significantly increases the
      reliability and sensitivity of immunodetection of CKI nuclear factors, and should
      be useful for both developmental neurobiology studies as well as cancer
      diagnostic applications.

PMID- 17024455
TI  - Identification of vitamin A-free cells in a stellate cell-enriched fraction of
      normal rat liver as myofibroblasts.
AB  - Myofibroblasts (MFs) as well as hepatic stellate cells (HSCs) are known to be
      involved in liver fibrogenesis. Quiescent HSCs (qHSCs) in culture have been
      thought to differentiate to replicative activated HSCs (aHSCs). In this study a
      qHSC-enriched fraction isolated by Nycodenz-isodensity centrifugation was
      separated with a fluorescence-activated cell sorter, which revealed the presence
      of a small fraction (occupancy rate=0.4%) of cells that did not show vitamin A
      autofluorescence under ultraviolet (UV)-irradiation (UV- cells). The remaining
      vitamin A-containing cells were autofluorescent (UV+) and originally expressed
      markers of qHSCs, and, in culture, did not grow, lost vitamin A, and expressed
      markers of aHSCs. UV- cells showed morphology of MFs, and, in culture, grew to
      form colonies and expressed markers of MFs. These results indicated that UV+ and
      UV- cells represent qHSCs and MFs, respectively, and that aHSCs have no growth
      potential and are a cell-type distinct from proliferative MFs. Gene expression
      profiles of UV- cells (MFs) newly identified gremlin as one of MF-preferential
      genes and its proteins were localized around fibrotic septa in rat and human
      livers. In addition, we suggested that the qHSC-enriched fraction included
      approximately 6% of liver MFs.

PMID- 17024456
TI  - Enzyme-assisted photosensitization with rose Bengal acetate induces structural
      and functional alteration of mitochondria in HeLa cells.
AB  - Rose Bengal acetate (RB-Ac) can be used as a fluorogenic substrate for
      photosensitization of cells both in vivo and in vitro: once inside the cells, RB
      Ac is converted into photoactive rose Bengal (RB) molecules which redistribute
      dynamically in the cytoplasm and, upon irradiation by visible green light, can
      damage organelles such as the endoplasmic reticulum, the Golgi apparatus, and the
      cytoskeleton. Recently, evidence has been provided that mitochondria may also be
      affected. The aims of the present study were to describe RB-induced photodamage
      of mitochondria in single HeLa cells and to define, on a quantitative basis, the
      effects of photosensitization on their morphofunctional features. HeLa cell
      cultures were exposed to 10(-5) M RB-Ac for 60 min and then irradiated with a
      light emitting diode at 530 nm (total light dose, 1.6 J/cm2). After irradiation,
      the cells were transferred to a drug-free complete medium and allowed to grow for
      24-72 h. Using conventional and confocal fluorescence microscopy, transmission
      electron microscopy, and flow cytometry, we demonstrate that, in photosensitized
      cells, mitochondria undergo structural and functional alterations which can lead
      cells to apoptosis. Interestingly, in our system some cells were able to survive
      72 h post-treatment and to recover, exhibiting the same mitochondrial structure,
      distribution and inner membrane potential as those in untreated controls. Taking
      into account that the photoactive molecules redistribute dynamically inside the
      cell upon RB-Ac administration, it may be hypothesized that cells can be
      differently affected by irradiation, depending on the relative amount and
      organelle location of the photosensitizer.

PMID- 17024457
TI  - [Imaging in the early diagnosis of changes in the hand of patients suffering from
      rheumatoid arthritis. Is ultrasound a true alternative for low-field magnetic
      resonance scanning, 3-phase bone scintigraphy and conventional x-rays?].
AB  - PURPOSE: Besides the use of conventional x-rays in the diagnostic work-up of
      initial changes in patients suffering from rheumatoid arthritis (RA), 3-phase
      bone scintigraphy (3P-Sz) is as well established as magnetic resonance imaging
      (MRI). The aim of this study was to compare the diagnostic value of ultrasound of
      the hands with proven methods such as conventional x-rays, low-field MRI and 3P
      Sz. METHODS: A total of 30 patients were studied using a 1 day protocol with
      ultrasound, 3P-Sz, MRI and x-ray of the hands. Images were visually assessed by
      two blinded nuclear medicine physicians and radiologists and classified as RA
      typical and non-RA typical changes. All methods were compared to the summarized
      findings interpreted by a rheumatologist after 2 years. RESULTS: Of the 30
      patients, 19 presented with clinical symptoms of initial changes due to
      rheumatoid arthritis. Ultrasound revealed 14/19 patients with the correct
      diagnosis. Conventional x-rays indicated 11/19 patients, while 3P-Sz (100%) and
      low-field MRI (95%) showed high sensitivity. It was possible to differentiate
      between inflammation and inconspicuous findings. CONCLUSIONS: An experienced
      examiner can use ultrasound effectively for the initial diagnosis of RA. Based on
      its low cost, ultrasound is a valid alternative to conventional x-rays.

PMID- 17024458
TI  - [Differential diagnosis in fever of unknown origin].
AB  - Fever is one of the most frequent and important symptoms in pediatrics. Most
      cases are caused by self-limiting viral or easily treatable bacterial infections.
      If after 5-7 days no cause of the ongoing fever has been found, the condition is
      termed fever of unknown origin, a working diagnosis which often poses a
      diagnostic challenge. The ultimate cause may be an infectious disease, a chronic
      inflammatory disorder, a malignancy, or another rare disease. The cause may also
      remain obscure or the fever can finally disappear. Here we elaborate the
      diagnostic work-up and symptomatic treatment.

PMID- 17024459
TI  - [Imaging in ankylosing spondylitis].
AB  - In addition to the typical clinical symptoms, conventional x-rays and magnetic
      resonance imaging (MRI) are important for the diagnosis and management of
      ankylosing spondylitis (AS). While radiography is mainly useful for detecting
      chronic structural changes, MRI is, in addition, able to detect active
      inflammation. The detection of structural changes in the sacroiliac joints and,
      in part, the spine, remains the gold standard for the diagnosis of AS. The
      detection of active sacroiliitis or spondylitis in early disease stages is only
      possible using MR techniques such as STIR and T1 post-gadolinium sequences.
      Lateral radiographs of the spine are useful for detecting shiny corners and the
      characteristic syndesmophytes and ankylosis. The modified Stoke Anklyosing
      Spondylitis Spine Score (SASSS) is the best scoring method for quantifying such
      changes, allthough only the cervical and the lumber spine are evaluated with this
      method. MRI changes can also be quantified. New scoring methods are sensitive to
      change only 3 months after initiation of therapy with anti-TNF agents.

PMID- 17024460
TI  - [Imaging procedures in rheumatology: imaging in vasculitis].
AB  - In small vessel vasculitides, imaging studies aid in determining disease extent
      and activity, localization for biopsy, and for disease monitoring. They do not
      directly delineate the vasculitic lesion. Imaging studies focus on the upper and
      lower respiratory tract. Cranial magnetic resonance imaging (MRI) shows upper
      respiratory and retrobulbar granuloma in Wegener's granulomatosis. Furthermore,
      MRI depicts both mastoiditis and mucosal inflammation of the ear, nose, and
      throat. It is sensitive but not specific for the detection of cerebral
      vasculitis. Computed tomography (CT) reliably detects osseous facial lesions.
      Chest radiography in two planes remains the standard method of investigation for
      the lower respiratory tract. High-resolution CT aids in detecting further
      interstitial pathologies. Medium-sized vasculitides frequently occur with
      aneurysms. The classification criteria for polyarteritis nodosa involve the
      angiographic detection of visceral aneurysms. Patients with Kawasaki disease may
      develop coronary aneurysms that may be described by echocardiography or
      angiography according to diagnostic criteria. In large-vessel vasculitides such
      as temporal arteritis (giant cell arteritis) and Takayasu arteritis, MRI, MR
      angiography, CT, CT-angiography, and duplex sonography delineate characteristic
      homogenous wall thickening with or without stenoses in the aorta and other
      arteries. There is a high correlation with angiography and positron emission
      tomography. Duplex sonography of the temporal arteries has a high sensitivity and
      specificity for the diagnosis. Data on temporal artery MRI in giant cell
      arteritis have recently been published.

PMID- 17024461
TI  - [The elder patient with a rheumatic disease and comorbidities. Aspects of
      rheumatology in an ageing population].
AB  - Elder patients with comorbidities are a rapidly growing population for in- and
      outpatient care. Diagnosis, treatment and integrated care are challenges which
      are only met by a multidisciplinary approach, which includes specialists from
      different medical professions and health professionals. A high number of
      comorbidities are a risk factor for drug interactions and fragmentisation of
      patient care between different medical disciplines. This is in particular
      relevant for patients with rheumatic diseases. So far it is not known whether
      treatment strategies such as the aim of remission induction in RA can be
      transferred as it is to the care of elder patients. Moreover, the safety and
      effectiveness of drugs used for the treatment of rheumatology patients has not
      yet been intensively studied. To meet the challenge of the care of a growing
      group of elder and multimorbid patients with rheumatic diseases, the
      reimbursement systems for in- and outpatient care must be adapted to allow
      multidisciplinary approaches. A concept for such a multidisciplinary procedure
      for inpatients with rheumatic diseases is introduced.

PMID- 17024462
TI  - Chondral fracture of the lateral trochlea of the femur occurring in an
      adolescent: mechanism of injury.
AB  - The trochlea of the femur is a very unusual site for chondral fracture. Little is
      known of the mechanism of injuries confined to the articular cartilage of the
      trochlea of the femur. A very unusual case of chondral fracture of the lateral
      trochlea of the femur occurring in an adolescent is reported here. The mechanism
      by which this injury occurred could be evaluated in this patient. The cartilage
      on the convex surface of the lateral trochlea was likely avulsed proximally by
      shear force of the patella during rapid extension of the weight-bearing knee from
      a flexed position. From a viewpoint of mechanism, this injury differs from the
      more usual osteochondral or chondral fractures of the weight bearing area of the
      femoral condyle, which are usually accompanied by twisting forces.

PMID- 17024463
TI  - Identification of the dimerisation interface of human interleukin-8 by IL-8
      variants containing the photoactivatable amino acid benzoyl-phenylalanine.
AB  - The three-dimensional structure of human interleukin-8 (hIL-8) was determined by
      the use of NMR and X-ray methodology. At high concentrations interleukin-8 and
      many other chemokines form a non-covalent homodimer. Several studies have been
      performed to investigate the relevance of the dimer on receptor activation and
      led to contradictory results. In order to obtain a better understanding of the
      dimerisation process, covalently linked homo- and heterodimers were produced by
      photo-induced dimerisation of hIL-8 analogues that contain the photo-activatable
      amino acid p-benzoyl-phenylalanine (Bpa) at different positions. Whereas the N
      terminal fragment (1-54) was expressed as recombinant thioester, the C-terminal
      fragments (55-77) that contain Bpa either at position 65 or 74 were obtained by
      solid-phase peptide synthesis. The segments were combined by expressed protein
      ligation and led to full length IL-8 variants containing the non-proteinogenic
      amino acid Bpa at single positions. IP(3) activity tests showed high biological
      activity for the CXCR1-GFP receptor for both variants comparable to that of the
      native ligand. The refolded and purified ligation-products were used for dimer
      formation by UV-irradiation. The analysis of the reaction mixture was performed
      by gel-electrophoresis and mass spectrometry and showed that dimer formation of
      IL-8 occurred in a position dependent manner. [Bpa(74)]hIL-8 has a high tendency
      to form covalent dimers whereas no dimer formation was observed for the variant
      with Bpa at position 65. Accordingly one residue of the dimerisation interface
      could be identified.

PMID- 17024464
TI  - Effects of acute carbohydrate supplementation during sessions of high-intensity
      intermittent exercise.
AB  - The present study evaluated the acute effects of carbohydrate supplementation on
      heart rate (HR), rate of perceived exertion (RPE), metabolic and hormonal
      responses during and after sessions of high-intensity intermittent running
      exercise. Fifteen endurance runners (26 +/- 5 years, 64.5 +/- 4.9 kg) performed
      two sessions of intermittent exercise under carbohydrate (CHO) and placebo (PLA)
      ingestion. The sessions consisted of 12 x 800 m separated by intervals of 1 min
      30 s at a mean velocity corresponding to the previously performed 3-km time
      trial. Both the CHO and PLA sessions were concluded within approximately 28 min.
      Blood glucose was significantly elevated in both sessions (123.9 +/- 13.2 mg dl(
      1) on CHO and 147.2 +/- 16.3 mg dl(-1) on PLA) and mean blood lactate was
      significantly higher in the CHO (11.4 +/- 4.9 mmol l(-1)) than in the PLA
      condition (8.4 +/- 5.1 mmol l(-1)) (P < 0.05). The metabolic stress induced by
      the exercise model used was confirmed by the elevated HR (approximately 182 bpm)
      and RPE (approximately 18 on the 15-point Borg scale) for both conditions. No
      significant differences in plasma insulin, cortisol or free fatty acids were
      observed during exercise between the two trials. During the recovery period, free
      fatty acid and insulin concentrations were significantly lower in the CHO trial.
      Supplementation with CHO resulted in higher lactate associated with lipolytic
      suppression, but did not attenuate the cortisol, RPE or HR responses.

PMID- 17024465
TI  - Gender differences and determinants of aerobic fitness in children aged 8-11
      years.
AB  - Previous studies of gender differences in maximum oxygen uptake have come to
      different conclusions. Limited data exists where the determinants of maximum
      oxygen uptake have been evaluated in a comprehensive manner. Thus, we examined
      248 children (140 boys and 108 girls), aged 7.9-11.1 years. Body composition was
      determined by dual-energy X-ray absorptiometry, measured variables were total
      body fat (TBF) and lean body mass (LBM). Maximal oxygen uptake (VO2peak) was
      measured by indirect calorimetry during a maximal cycle exercise test. Daily
      physical activity was assessed by accelerometers and duration of vigorous
      activity per day (VPA) was calculated. Left ventricular inner diastolic diameter
      (LVDD) was measured by echocardiography. Lung function was evaluated with
      spirometric testing and whole body plethysmography. Boys had between 8 and 18%
      higher values than girls for VO2peak, dependent upon whether VO2peak was
      expressed in absolute values or scaled to body mass, LBM or if allometric scaling
      was used. In multiple regression analysis absolute values of aerobic fitness were
      independently related to LBM, maximal heart rate (Max HR), gender, LVDD, and VPA.
      Furthermore, when VO2peak was scaled to body mass it was independently related to
      ln TBF, Max HR, gender, VPA, and LVDD. Lung function had no relation to VO2peak.
      Our study concludes that body composition is the main predictor for VO2peak, in
      children aged 8-11 years, whereas VPA or LVDD has only a modest impact. Existing
      gender differences in VO2peak cannot be explained only by differences in body
      composition, physical activity, or heart size.

PMID- 17024466
TI  - Effects of graded levels of exercise on ipsilateral and contralateral post
      exercise resting rectus femoris mechanomyography.
AB  - Mechanomyography has shown that "resting" muscle is mechanically active, with
      greater activity after vigorous exercise. This experiment studied the post
      exercise resting mechanomyography activity that results from different levels of
      exercise; the effects of exercise levels on the contralateral non-exercised limb;
      and the effects of resting muscle length on post-exercise resting
      mechanomyographic activity. Ten healthy volunteers had mechanomyography
      recordings over both mid-rectus femoris, at rest, before and after sets (1, 5,
      10, 20, and 30 repetitions) of right leg extensions on an isokinetic dynamometer
      at 60 s(-1). Sets were performed a week apart, after only sedentary activity
      during the previous two hours. No definite threshold effect was shown. There was
      a linear correlation between mechanomyography and work done (R = 0.61, P < 0.01).
      There was a positive correlation of change of activity between the two thighs (R
      = 0.62, P < 0.01), with the non-exercised thigh demonstrating about half the
      activity of the exercised thigh. Finally, we observed that mechanomyographic
      activity was greater when rectus femoris muscle length was shorter (i.e. when the
      leg was extended versus flexed). We conclude that resting mechanomyography
      increases with increasing work and that there is a cross-over for increase in
      mechanomyography in the non-exercised leg, suggesting a neural mechanism. The
      greater mechanomyographic activity at shorter muscle lengths suggests that muscle
      that is less stretched could more freely oscillate, producing higher MMG
      amplitudes. Altered activity of the muscle spindle gamma loop or Golgi tendon
      apparatus may also play a role in altered activity with different muscle length.

PMID- 17024467
TI  - Adaptive potential of human biceps femoris muscle demonstrated by histochemical,
      immunohistochemical and mechanomyographical methods.
AB  - The goal of this study was to estimate the ability of biceps femoris (BF) muscle,
      a hamstring muscle crucial for biarticulate movement, to adapt to changed
      functional demands. For this purpose and due to ethical reasons, in a group of
      healthy sedentary men and of 15 sprinters, a non-invasive mechanomyography (MMG)
      method was used to measure the muscle twitch contraction times (Tc). These
      correlate with the proportions of slow and fast fibres in the muscle. To further
      elucidate the data obtained by MMG method and to obtain reference data for the
      muscle, the fiber type proportions in autoptic samples of BF in sedentary young
      men were determined according to histochemical reaction for myofibrillar
      adenosine triphosphatase (mATPase). In one BF sample also myosin heavy chain
      (MyHC) isoform expression was demonstrated immunohistochemically. With MMG we
      indirectly demonstrated that biceps femoris muscle has a strong potential to
      transform into faster contracting muscle after sprint training, since the average
      Tc in sprinters was much lower (19.5 +/- 2.3 ms) than in the sedentary group
      (30.25 +/- 3.5 ms). The results of the histochemical and immunohistochemical
      analysis of BF muscle also imply a high adapting potential of this muscle. Beside
      type 1, 2a and 2x (2b) fibres a relatively high proportion of intermediate type
      2c fibres (5.7% +/- 0.7), which co-expressed MyHC-1 and -2a, was found.
      Therefore, type 2c might represent a potential pool of fibres, capable of
      transformation either to slow type 1 or to fast type 2a in order to tune the
      functional response of BF muscle according to the actual functional demands of
      the organism.

PMID- 17024468
TI  - Biofiltration of toluene-contaminated air using an agro by-product-based filter
      bed.
AB  - An innovative, coir-pith-based, filter bed for degrading vapor phase toluene in a
      gas biofilter over 160 days without any external nutrient supply is reported in
      this study. Indigenous microflora present in the coir pith as well as in the
      aerobic sludge added at the start-up stage metabolized the toluene, and
      correspondingly, CO(2) was produced in the biofilter. Inlet toluene concentration
      in the range of 0.75 to 2.63 g/m(3) was supplied to the biofilter in short
      acclimation periods. The maximum elimination capacity achieved was 96.75 g/m(3) x
      h at 120.72 g/m(3) x h loading where around 60% was recovered as CO(2). The
      filter bed maintained a stable low-pressure drop (0-4 mm H(2)O), neutral pH range
      (6.5-7.5), and moisture content of 60-80% (w/w) throughout the period. In
      addition to toluene-degrading microbial community, a grazing fauna including
      rotifer, bacteriovoric nematode, tardigrade, and fly larvae were also present in
      the filter bed. The overall performance of the biofilter bed in pollutant removal
      and sustainability was analyzed in this study.

PMID- 17024469
TI  - A simple preparation method of crystals of soybean hull peroxidase.
AB  - Soybean hull peroxidase (SHP) was crystallised from an enzyme solution with low
      purity by a simple method. The enzyme solution was purified by cooperation
      salting out of acetone and ammonium sulphate, and lumpy crystals were obtained
      with the size of about 40 x 30 mum when ammonium sulphate was quickly added to
      the enzyme solution. The crystal was examined and confirmed to be an SHP crystal
      by the method of activity test. The result shows that, though the purity of the
      enzyme solution was not high, crystals could be formed when the enzyme solution
      rapidly reached to a degree of supersaturation, which was different from the
      traditional methods of protein crystallisation. Additionally, a purification
      method of acetone and ammonium sulphate fractional salting out was also studied,
      in which the procedure was simplified, and a satisfactory purification effect was
      obtained.

PMID- 17024470
TI  - Applicability of pectate-entrapped Lactobacillus casei cells for L(+) lactic acid
      production from whey.
AB  - Lactic acid is a versatile organic acid, which finds major application in the
      food, pharmaceuticals, and chemical industries. Microbial fermentation has the
      advantage that by choosing a strain of lactic acid bacteria producing only one of
      the isomers, an optically pure product can be obtained. The production of L: (+)
      lactic acid is of significant importance from nutritional viewpoint and finds
      greater use in food industry. In view of economic significance of immobilization
      technology over the free-cell system, immobilized preparation of Lactobacillus
      casei was employed in the present investigation to produce L: (+) lactic acid
      from whey medium. The process conditions for the immobilization of this bacterium
      using calcium pectate gel were optimized, and the developed cell system was found
      stable during whey fermentation to lactic acid. A high lactose conversion
      (94.37%) to lactic acid (32.95 g/l) was achieved with the developed immobilized
      system. The long-term viability of the pectate-entrapped bacterial cells was
      tested by reusing the immobilized bacterial biomass, and the entrapped bacterial
      cells showed no decrease in lactose conversion to lactic acid up to 16 batches,
      which proved its high stability and potential for commercial application.

PMID- 17024471
TI  - Bacterial expression of a Trichosanthes kirilowii defensin (TDEF1) and its
      antifungal activity on Fusarium oxysporum.
AB  - The gene encoding Trichosanthes kirilowii defensin (TDEF1) was cloned by reverse
      transcriptase-polymerase chain reaction (RT-PCR). The newly discovered TDEF1 cDNA
      contains 231 bp (Genbank accession number DQ526373) and encodes a 76-amino acid
      protein, which consists of a 29-amino acid signal peptide and a 47-amino acid
      mature peptide. The partial cDNA, corresponding to the mature peptide coding
      region of TDEF1, was inserted into bacterial expression vector pET32a(+).
      Subsequent expression showed that TDEF1 was produced as a 26-kDa fusion protein
      in the form of inclusion body in Escherichia coli BL21 (DE3). After protein
      refolding and purification, the fusion TDEF1 displayed an inhibitive activity
      against the fungal pathogen, Fusarium oxysporum, with EC(50) of 247 microg/ml by
      means of fungal growth inhibition method.

PMID- 17024472
TI  - A new approach to the production of the recombinant SOD protein by methylotrophic
      Pichia pastoris.
AB  - The gene for the copper, zinc-superoxide dismutase (SOD) from the yeast
      Saccharomyces cerevisiae was cloned, characterized, and overexpressed in the
      methylotrophic Pichia pastoris. The sod gene sequence obtained is 465 bp and
      encodes 154 amino acid residues. The sod gene sequence was cloned into the pPIC9K
      vector, yielding pAB22. The linearized pAB22 DNA, digested with restriction
      enzyme SacI, was transformed into the genome of the GS115 strain of yeast P.
      pastoris. The overexpressed SOD protein was shown to have immunologically
      biological activity and to be enzymatically active. The SOD protein was purified
      from the cultured yeast by ammonium sulfate precipitation and diethylaminoethyl
      cellulose column chromatography. This relatively simple purification method
      produced a single band on analysis by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), which indicated that the SOD protein obtained
      attained to higher purity and specific activity.

PMID- 17024473
TI  - Reducing haziness in white wine by overexpression of Saccharomyces cerevisiae
      genes YOL155c and YDR055w.
AB  - Grape proteins aggregate in white wine to form haze. A novel method to prevent
      haze in wine is the use of haze protective factors (Hpfs), specific mannoproteins
      from Saccharomyces cerevisiae, which reduce the particle size of the aggregated
      proteins. Hpf1p was isolated from white wine and Hpf2p from a synthetic grape
      juice fermentation. Putative structural genes, YOL155c and YDR055w, for these
      proteins were identified from partial amino acid sequences of Hpf1p and Hpf2p,
      respectively. YOL155c also has a homologue, YIL169c, in S. cerevisiae. Comparison
      of the partial amino acid sequence of deglycosylated-Hpf2p with the deduced
      protein sequence of YDR055w, confirmed five of the 15 potential N-linked
      glycosylation sites in this sequence were occupied. Methylation analysis of the
      carbohydrate moieties of Hpf2p indicated that this protein contained both N- and
      O-linked mannose chains. Material from fermentation supernatant of deletion
      strains had significantly less activity than the wild type. Moreover, YOL155c and
      YIL169c overexpressing strains and a strain overexpressing 6xHis-tagged Hpf2p
      produced greater haze protective activity than the wild type strains. A storage
      trial demonstrated the short to midterm stability of 6xHis-tagged Hpf2p in wine.

PMID- 17024474
TI  - The prokaryotic cytoskeleton: a putative target for inhibitors and antibiotics?
AB  - In the recent decade, our view on the organization of the bacterial cell has been
      revolutionized by the identification of cytoskeletal elements. Most bacterial
      species have structural homologs of actin and tubulin that assemble into dynamic,
      filamentous structures at precisely defined sub-cellular locations. The essential
      cell division protein FtsZ forms a dynamic ring at mid-cell and is similar in its
      structure to tubulin. Proteins of the MreB family, which are structural homologs
      of actin, assemble into helical or straight filaments in the bacterial cytoplasm.
      As in eukaryotic cells, the bacterial cytoskeleton drives essential cellular
      processes such as cell division, cell wall growth, DNA movement, protein
      targeting, and alignment of organelles. Different high-throughput assays have
      been developed to search for inhibitors of components of the bacterial
      cytoskeleton. Cell-based assays for the detection of cell division inhibitors as
      well as FtsZ GTPase assays led to the identification of several compounds that
      inhibit the polymerization of FtsZ, by this blocking bacterial cell division.
      Such inhibitors might not only be valuable tools for basic research, but might
      also lead to novel therapeutic agents against pathogenic bacteria. For example,
      the polyphenol dichamanetin, the 2-alkoxycarbonylaminopyridine SRI-3072, and the
      benzophenanthridine alkaloid sanguinarine inhibit the GTPase activity of FtsZ and
      exhibit antimicrobial activity.

PMID- 17024475
TI  - The methionine synthase reductase 66A>G polymorphism is a maternal risk factor
      for spina bifida.
AB  - The methionine synthase reductase (MTRR) enzyme restores methionine synthase
      (MTR) enzyme activity and therefore plays an essential role in homocysteine
      remethylation. In some studies, the 66A>G polymorphism in the MTRR gene was
      associated with increased neural tube defect (NTD) risk. Using a case-control
      design, we studied the association between the MTRR 66A>G polymorphism and spina
      bifida risk in 121 mothers, 109 spina bifida patients, 292 control women, and 234
      pediatric controls. Possible interactions between the MTRR 66A>G variant and the
      MTR 2756A>G polymorphism, the MTHFR 677C>T variant, plasma vitamin B12, and
      plasma methylmalonic acid (MMA) levels were examined in the 121 mothers and 292
      control women. Meta-analyses were conducted to set the results of the case
      control study in the context of eligible literature on the relation between the
      MTRR 66A>G variant and NTD risk. Finally, a transmission disequilibrium test was
      performed for 82 complete mother-father-child triads to test for preferential
      transmission of the MTRR risk allele. In our case-control study, the MTRR 66A>G
      polymorphism had no influence on spina bifida risk in children [odds ratio (OR)
      0.6, 95% confidence interval (CI) 0.4-1.1]. The MTRR 66GG genotype increased
      maternal spina bifida risk by 2.1-fold (OR 2.1, 95% CI 1.3-3.3). This risk became
      more pronounced in combination with the MTHFR 677TT genotype (OR 4.0, 95% CI 1.3
      12.5). Moreover, we demonstrate a possible interaction between the MTRR 66GG
      genotype and high plasma MMA levels (OR 5.5, 95% CI 2.2-13.5). The meta-analyses
      demonstrated that the maternal MTRR 66GG genotype was associated with an overall
      55% (95% CI 1.04-2.30) increase in NTD risk and that the MTRR 66GG genotype did
      not increase NTD risk in children (OR 0.96, 95% CI 0.46-2.01). These data show
      that the MTRR 66GG genotype is a maternal risk factor for spina bifida especially
      when intracellular vitamin B12 status is low.

PMID- 17024476
TI  - Arthroscopic assisted reduction and internal fixation of lateral femoral
      epiphyseal injury in adolescent soccer player: a report of one case.
AB  - Ligament injuries are more common than fractures in adolescents. We operated on
      an adolescent soccer player, who had a lateral femoral epiphyseal injury using
      arthroscopic-assisted reduction and percutaneous internal fixation. During second
      look arthroscopy 2 years after the first operation, there was articular cartilage
      congruity, without any visible step-off. The axial alignment did not reveal any
      residual valgus deformity.

PMID- 17024477
TI  - An en bloc avulsion fracture of tibial tuberosity and Gerdy's tubercle in an
      adolescent basketball player: a case report.
AB  - We report a case of en bloc avulsion fracture of tibial tuberosity and Gerdy's
      tubercle, which has never been reported. A 14-year-old boy suffered from an acute
      pain in his left knee during running just before a jump. Simple radiographs
      showed an avulsion of the tibial tuberosity. On CT scans, the fractured fragment
      was attached not only to patellar tendon but also to iliotibial band (ITB) via
      Gerdy's tubercle. MRI evaluation revealed no intra-articular associated
      pathology. Open reduction and internal fixation with three cannulated screws were
      performed under lateral parapatellar approach to expose both the tibial
      tuberosity with patellar tendon and Gerdy's tubercle with ITB. At postoperative 1
      year, he could walk, run, squat, and complained of no difficulty in activities on
      daily living with full range-of-motion of the knee. Radiographs showed well
      healed fracture in situ. Gradually, he returned to sports activity. We believe
      that the injury was caused by the dynamic pull of quadriceps muscle via patellar
      tendon onto tibial tuberosity and the mostly static pull of ITB onto Gerdy's
      tubercle, both of which took a part in the fracture of the anterolateral portion
      of the unfused epiphysis of proximal tibia. The pes anserinus attaching on the
      anteromedial metaphysis of proximal tibia might exert the opposing deforming
      force. Preoperative planning including the determination of the extent of
      fracture and recognition of concomitant injury is a prerequisite for appropriate
      treatment.

PMID- 17024478
TI  - A rare cause for knee pain: fracture of the femoral component after TKR. A case
      report.
AB  - We report the rare case of sudden knee pain due to fracture of the total knee
      replacement nine years after implantation. Fracture occurred because of
      subsequent osteolysis due to polyethylene wear.

PMID- 17024479
TI  - [Idiopathic thunderclap headache: reversible vasospasm of the Arteria basilaris].
AB  - Thunderclap headache describes a rare headache syndrome characterized by abrupt
      onset severe headache mimicking subarachnoidal bleeding, which has to be excluded
      by adequate diagnostic procedures such as digital subtraction angiography. The
      pathophysiology is still not clear but there are an increasing number of reports
      which describe some kind of vasospasm of the intracranial arteries during the
      headache episode. Here we describe a patient with a thunderclap headache and a
      mid-basilar narrowing due to a reversible vasospasm.

PMID- 17024480
TI  - [Insufficient involvement of psychiatrists in substitution treatment].
AB  - Results of a nationally representative study in 2,694 patients reveal that most
      physicians (n=223) involved in substitution treatment of opioid-dependent
      patients are general practitioners, while only 16% have a
      psychiatric/psychotherapeutic background and only 21% of the addictive patients
      are treated by psychiatrists. This contrasts with the remarkably complex pattern
      of co- and multimorbidity with other mental disorders in such patients. Most
      psychiatrists engaged in substitution treatment work in specialized outpatient
      wards (51.3%), and few were operative in their own or private practice (7.2%).
      Implications of these critical findings are discussed.

PMID- 17024482
TI  - [DGPPN news. Declaration of Helsinki--a challenge for German psychiatry].

PMID- 17024483
TI  - Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during
      imatinib mesylate treatment.
AB  - PURPOSE: Imatinib mesylate showed a sustained objective response in patients with
      advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001.
      Here we reported genetic changes during imatinib mesylate treatment especially
      when the patient had partial response or stationary disease. MATERIALS AND
      METHODS: Between 2001 and June 2005, 44 advanced GIST patients were treated with
      imatinib mesylate. Among them, five patients (11.9%) (four with partial response
      and one with stationary disease) received surgical treatment during imatinib
      mesylate treatment. We compared the genetic status of each tumor in the five
      patients before and after imatinib mesylate treatment. RESULTS: Symptomatic
      gallbladder stone with or without cholecystitis (two patients), lower GI bleeding
      (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one
      patient) comprised the indications for operation. Before imatinib mesylate
      treatment, four of the five patients displayed deletion mutation and one patient
      displayed point mutation in exon 11. After treatment, one patient developed
      second novel missense mutation in exon 17 with acquired resistance since he was
      administered with only half dose of imatinib mesylate. The other four patients
      taking the same dose of imatinib mesylate exhibited identical mutation to the
      previous lesions. CONCLUSIONS: Necrosis of large and bulky tumors after imatinib
      mesylate therapy might be the reason of gastrointestinal hemorrhage and
      enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could
      induce acquired resistance during treatment and second novel mutation might be
      the reason.

PMID- 17024484
TI  - Nasal carriage of pathogenic bacteria in medical students: effects of clinic
      exposure on prevalence and antibiotic susceptibility.
AB  - Staphylococcus aureus is a major cause of community-acquired and nosocomial
      infections worldwide. One important source of this pathogen for nosocomial
      infections is the nasal carriage of S. aureus among hospital personnel. There are
      only a few studies investigating the carriage of S. aureus in a community of
      medical students. Oral and nasal flora of 179 medical students with varying
      clinical exposures were determined. Oral cultures revealed no nosocomial pathogen
      and nasal cultures showed an increasing rate of S. aureus carriage with
      increasing clinical exposure. Methicillin resistance also demonstrated a tendency
      toward increasing with increasing clinical exposure.

PMID- 17024485
TI  - The frequency of inappropriate tablet splitting in primary care.
AB  - INTRODUCTION: We assessed the frequency and determinants of tablet splitting in
      primary care in Germany and evaluated the quality of information on divisibility
      in the Summary of Product Characteristics (SPCs) and in the Package Leaflet (PL)
      as legal sources of information for health care providers and patients. METHODS:
      We performed a cross-sectional questionnaire survey among patients of 59 general
      practitioners in the German Federal State Saxony-Anhalt in 2005 in order to
      collect detailed information on all drugs of patients maintained on more than
      three drugs. RESULTS: The response rate was 82.1% (n=905) and 3,158 drugs
      (tablets and dragees) were included in the analyses. Of all drugs, 24.1% were
      split (762 of 3,158): 8.7% of all split tablets were unscored (66 of 762) and
      3.8% of all split tablets were not allowed to be split (29 of 762). Tablets of
      the higher price categories and higher strengths were twice as likely to be
      split. Only 22.5% of the SPCs (9 of 40) of the split unscored tablet brands
      contained explicit information on divisibility and only 36.4% of the PLs (8 of
      22) of the split brands that were not allowed to be split stated that splitting
      was not appropriate. CONCLUSION: The splitting of tablets in primary care is a
      frequent habit likely driven by medical and economic considerations. Almost 1% of
      all tablets are split that must not be fragmented. However, the SPC and PL
      provide only limited information on divisibility stressing the need to improve
      this information promptly to avoid medication errors.

PMID- 17024486
TI  - Pamidronate distribution in pediatric renal and rheumatologic patients.
AB  - OBJECTIVE: To evaluate the distribution and elimination of pamidronate in a
      population of pediatric patients with renal and rheumatologic disease. METHODS:
      Pamidronate whole blood levels were collected for the first 4 h after first
      exposure in 7 patients. The relationship between the rate of urinary excretion of
      pamidronate and bone formation or resorption was examined in 18 patients while
      receiving pamidronate at a total dose of 1 mg/kg/dose infused intravenously over
      a 4-h period. The urinary pamidronate clearances were correlated with renal
      function, calcium levels and measures of bone formation and resorption. RESULTS:
      Pamidronate levels reached steady state concentrations of 0.9-1.5 microg/ml
      within 30 min and the clearance of the drug (mean+/-SE) from blood was 180.0+/
      64.2 ml/kg/h with an elimination half-life of less than 1 h. The mean urinary
      excretion of 31.5+/-2.2% of the administered dose indicated that about 68% of the
      drug was incorporated into bone, confirming the uptake of pamidronate into bone
      was similar in pediatric patients compared to that previously reported for
      adults. Bone specific alkaline phosphatase, which is a marker for bone growth and
      formation, had significant correlation with the uptake of pamidronate into bone
      (p=0.002). No correlation was demonstrated with a marker for bone resorption
      (urinary N-telopeptide/creatinine ratio), or with creatinine clearance or
      calciuria when assessed 2 months after treatment. CONCLUSION: Pamidronate at a
      dose of 1 mg/kg/dose every 2 months appears safe in the short term for pediatric
      patients, achieves relatively low whole blood pamidronate levels, and has similar
      skeletal uptake of pamidronate compared to adults.

PMID- 17024487
TI  - Factor analysis improves the selection of prescribing indicators.
AB  - OBJECTIVE: To test a method for improving the selection of indicators of general
      practitioners' prescribing. METHODS: We conducted a prescription database study
      including all 180 general practices in the County of Funen, Denmark,
      approximately 472,000 inhabitants. Principal factor analysis was used to model
      correlation between 19 register-based indicators for the quality of non-steroidal
      anti-inflammatory drug (NSAID) prescribing. RESULTS: The correlation between
      indicators ranged widely from 0 to 0.93. Factor analysis revealed three
      dimensions of quality: (1) "Coxib preference", comprising indicators directly
      quantifying choice of coxibs, indicators measuring expenditure per Defined Daily
      Dose, and indicators taking risk aspects into account, (2) "Frequent NSAID
      prescribing", comprising indicators quantifying prevalence or amount of NSAID
      prescribing, and (3) "Diverse NSAID choice", comprising indicators focusing on
      the width of GPs' formularies. The number of indicators for measuring the
      important aspects of quality in prescribing of NSAIDs could be reduced
      substantially by selecting the indicator in each dimension with the highest
      factor loading. A high preference for coxibs indicated both appropriate and
      inappropriate prescribing, as revealed by the correlation of the indicators in
      the first factor. CONCLUSION: Correlation and factor analysis is a feasible
      method that assists the selection of indicators and gives better insight into
      prescribing patterns.

PMID- 17024488
TI  - A meta-analysis of ECG data from healthy male volunteers: diurnal and intra
      subject variability, and implications for planning ECG assessments and
      statistical analysis in clinical pharmacology studies.
AB  - OBJECTIVE: To evaluate the innate variability in key electrocardiography (ECG)
      parameters from clinical pharmacology studies. METHODS: Meta-analysis of ECG data
      from seven clinical pharmacology studies in healthy male volunteers using model
      building and stepwise multiple regression analyses. RESULTS: Data from 115 male
      subjects provided over 2,000 observations for all key ECG parameters from
      baseline (Day-1) and placebo treatment periods (Day 1). Only heart rate and
      uncorrected QT showed clear and marked changes over the day. QTcB had greater
      variability compared to QTcF. 1.4% of QTcB and 0.7% QTcF observations were >430
      ms and 0.1% of QTcB and 0% of QTcF observations were >450 ms. We estimated that
      8.9% of subjects would have at least one out of eight post-observation QTc value
      in the range 430-450 ms [assuming QTc mean 385 ms, standard deviation (SD) 20 ms]
      due to intrinsic variability alone. Time-matched within-subjects observations
      demonstrated that the SD between measurements taken 1 h apart was less than seen
      with a longer interval, but there was little increase in variability beyond 1 h.
      The probability of observing an increase in QTc of 30-60 ms in a subject was
      estimated as 3.0% and 21.8% for one and eight post-dose observations,
      respectively. The greater the number of observations used to define baseline the
      narrower the spread; for QTcF the SD of the baseline value was 17.1 ms for a
      single assessment, 13.3 ms for the mean of three assessments, and 13.2 ms for the
      mean of all Day-1 assessments. CONCLUSIONS: The spontaneous variability in QTc
      measurements must be taken into account when designing studies and interpreting
      analyses of ECG data. The categorical analysis of QTc change of 30-60 ms is
      unlikely to be of any additional value to analyses of central tendency. For
      standard early clinical pharmacology studies, QTcF should be chosen as the
      primary correction method, while the mean of three measures taken in the
      afternoon and evening of Day-1 and pre-dose Day 1 should provide a reliable and
      representative baseline assessment.

PMID- 17024489
TI  - Mutation in cyaA in Enterobacter cloacae decreases cucumber root colonization.
AB  - Strains of Enterobacter cloacae show promise as biological control agents for
      Pythium ultimum-induced damping-off on cucumber and other crops. Enterobacter
      cloacae M59 is a mini-Tn5 Km transposon mutant of strain 501R3. Populations of
      M59 were significantly lower on cucumber roots and decreased much more rapidly
      than those of strain 501R3 with increasing distance from the soil line. Strain
      M59 was decreased or deficient in growth and chemotaxis on most individual
      compounds detected in cucumber root exudate and on a synthetic cucumber root
      exudate medium. Strain M59 was also slightly less acid resistant than strain
      501R3. Molecular characterization of strain M59 demonstrated that mini-Tn5 Km was
      inserted in cyaA, which encodes adenylate cyclase. Adenylate cyclase catalyzes
      the formation of cAMP and cAMP levels in cell lysates from strain M59 were
      approximately 2% those of strain 501R3. Addition of exogenous, nonphysiological
      concentrations of cAMP to strain M59 restored growth (1 mM) and chemotaxis (5 mM)
      on synthetic cucumber root exudate and increased cucumber seedling colonization
      (5 mM) by this strain without serving as a source of reduced carbon, nitrogen, or
      phosphorous. These results demonstrate a role for cyaA in colonization of
      cucumber roots by Enterobacter cloacae.

PMID- 17024490
TI  - Multiple regulators of the Flavohaemoglobin (hmp) gene of Salmonella enterica
      serovar Typhimurium include RamA, a transcriptional regulator conferring the
      multidrug resistance phenotype.
AB  - Microbial flavohaemoglobins are proteins with homology to haemoglobins from
      higher organisms, but clearly linked to nitric oxide (NO) metabolism by bacteria
      and yeast. hmp mutant strains of several bacteria are hypersensitive to NO and
      related compounds and hmp genes are up-regulated by the presence of NO. The
      regulatory mechanisms involved in hmp induction by NO and the superoxide
      generating agent, methyl viologen (paraquat; PQ), are complex, but progressively
      being resolved. Here we show for the first time that, in Salmonella enterica
      serovar Typhimurium, hmp transcription is increased on exposure to PQ and
      demonstrate that RamA, a homologue of MarA is responsible for most of the hmp
      paraquat regulation. In addition we demonstrate NO-dependent elevation of
      Salmonella hmp transcription and Hmp accumulation. In both Escherichia coli and
      Salmonella modest transcriptional repression of hmp is exerted by the iron
      responsive transcriptional repressor Fur. Finally, in contrast to previous
      reports, we show that in E. coli and Salmonella, hmp induction by both paraquat
      and sodium nitroprusside is further elevated in a fur mutant background,
      indicating that additional regulators are implicated in this control process.

PMID- 17024491
TI  - Acute suppurative thyroiditis.

PMID- 17024492
TI  - Isolated filar cyst on lumbar spine sonography in infants: a case-control study.
AB  - BACKGROUND: Simple cysts found within the filum terminale of infants on lumbar
      spine sonography are relatively common, but no study has established their
      clinical significance. OBJECTIVE: To obtain information on the sonographic
      features of isolated filar cysts and determine their clinical significance in
      comparison with age- and sex-matched controls. MATERIALS AND METHODS: We
      performed a retrospective review of 644 consecutive spine sonograms in patients
      younger than 8 months. Gestational age- and sex-matched controls with normal
      lumbar sonograms were taken from the same period. We obtained short-term clinical
      follow-up of motor milestones for each group. RESULTS: The incidence of filar
      cyst was 78 of the 644 (11.8%) and was inversely related to age. Developmental
      follow-up of the study patients compared with control population showed no
      statistically significant difference in the ages at which the infants were able
      to turn over, crawl and walk. Follow-up MR imaging of 13 study patients (19%)
      failed to demonstrate filar cysts previously identified on sonography.
      CONCLUSION: No significant difference was found in the short-term outcome of
      infants with isolated filar cysts on lumbar sonography compared with that of a
      control population. Filar cysts should be considered a normal variant when found
      in isolation on lumbar sonography.

PMID- 17024493
TI  - Platinum(II) complexes interfering with testicular steroid biosynthesis: drugs
      for the therapy of advanced or recurrent prostate cancers? Preclinical studies.
AB  - [Meso-1,2-bis(2,6-dihalo-3/4-hydroxyphenyl)ethylenediamine]platinum(II) complexes
      (meso-1-PtLL': 2,6-F(2),3-OH; meso-2-PtLL': 2,6-F(2),4-OH; meso-3-PtLL': 2,6
      Cl(2),3-OH; meso-4-PtLL': 2,6-Cl(2),4-OH; L = OH(2), L' = OSO(3) or L,L' = Cl(2))
      were designed with the aim to get drugs comprising both cytotoxic and
      testosterone level lowering potencies. It is assumed that such compounds are more
      efficient than the established endocrine therapeutic measures and can affect the
      development of hormone refractory prostate cancer (PC). With exception of meso-3
      PtLL' all Pt-complexes and the comparison compound cisplatin significantly
      reduced the testosterone level in experiments on male rats. However, in the test
      on the Dunning R3327 PC of the rat only cisplatin and meso-4-PtLL' showed a
      significant anti-tumor activity at well-tolerated dose ranges. Meso-4-PtLL' also
      significantly extended the time to disease progression in comparison with
      orchiectomy in this tumor model. Interestingly, the relapsed tumor, too,
      responded to meso-4-PtLL' as demonstrated in a long-term study on orchiectomized
      rats bearing Dunning R3327 PC grafts. This effect cannot be ascribed to cytotoxic
      effects of meso-4-PtLL' because of its inactivity on the human LNCaP/FGC PC cell
      line. Therefore, the contribution of an additional mechanism to the anti-prostate
      cancer activity of meso-4-PtLL', presumably owing to its estrogenic potency, must
      be considered. This assumption was supported by test results with
      diethylstilbestrol (DES) (non-steroidal estrogen) on the Dunning R3327 PC of the
      rat relapsed after orchiectomy. This tumor model was strongly inhibited by DES.
      The possible mode of action of meso-4-PtLL' is thoroughly discussed.

PMID- 17024495
TI  - The muscle protein dysferlin accumulates in the Alzheimer brain.
AB  - Dysferlin is a transmembrane protein that is highly expressed in muscle.
      Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and
      distal anterior compartment myopathy. Dysferlin has also been described in neural
      tissue. We studied dysferlin distribution in the brains of patients with
      Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical
      Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease
      duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years).
      Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD
      brains. In addition, there were dysferlin-positive dystrophic neurites within A
      beta plaques in the AD brain, distinct from tau-positive neurites. Western blots
      of total brain protein (RIPA) and sequential extraction buffers (high salt, high
      salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength
      were performed to examine solubility state. In RIPA fractions, dysferlin was seen
      as 230-272 kDa bands in normal and AD brains. In serial extractions, there was a
      shift of dysferlin from soluble phase in high salt/Triton X-100 to the more
      insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD
      brain that accumulates in association with neuritic plaques. In muscle, dysferlin
      plays a role in the repair of muscle membrane damage. The accumulation of
      dysferlin in the AD brain may be related to the inability of neurons to repair
      damage due to A beta deposits accumulating in the AD brain.

PMID- 17024494
TI  - Neurolysosomal pathology in human prosaposin deficiency suggests essential
      neurotrophic function of prosaposin.
AB  - A neuropathologic study of three cases of prosaposin (pSap) deficiency (ages at
      death 27, 89 and 119 days), carried out in the standard autopsy tissues, revealed
      a neurolysosomal pathology different from that in the non-neuronal cells. Non
      neuronal storage is represented by massive lysosomal accumulation of
      glycosphingolipids (glucosyl-, galactosyl-, lactosyl-, globotriaosylceramides,
      sulphatide, and ceramide). The lysosomes in the central and peripheral neurons
      were distended by pleomorphic non-lipid aggregates lacking specific staining and
      autofluorescence. Lipid storage was borderline in case 1, and at a low level in
      the other cases. Neurolysosomal storage was associated with massive
      ubiquitination, which was absent in the non-neuronal cells and which did not
      display any immunohistochemical aggresomal properties. Confocal microscopy and
      cross-correlation function analyses revealed a positive correlation between the
      ubiquitin signal and the late endosomal/lysosomal markers. We suppose that the
      neuropathology most probably reflects excessive influx of non-lipid material
      (either in bulk or as individual molecules) into the neurolysosomes. The cortical
      neurons appeared to be uniquely vulnerable to pSap deficiency. Whereas in case 1
      they populated the cortex, in cases 2 and 3 they had been replaced by dense
      populations of both phagocytic microglia and astrocytes. We suggest that this
      massive neuronal loss reflects a cortical neuronal survival crisis precipitated
      by the lack of pSap. The results of our study may extend the knowledge of the
      neurotrophic function of pSap, which should be considered essential for the
      survival and maintenance of human cortical neurons.

PMID- 17024496
TI  - Differences in expression of junctional adhesion molecule-A and beta-catenin in
      multiple sclerosis brain tissue: increasing evidence for the role of tight
      junction pathology.
AB  - Previously we have employed antibodies to the tight junction (TJ)-associated
      proteins ZO-1 and occludin to describe endothelial tight junction abnormalities,
      in lesional and normal appearing white matter, in primary and secondary
      progressive multiple sclerosis (MS). This work is extended here by use of
      antibodies to the independent TJ-specific proteins and junctional adhesion
      molecule A & B (JAM-A, JAM-B). We have also assessed the expression in MS of beta
      catenin, a protein specific to the TJ-associated adherens junction.
      Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and beta
      catenin was performed on snap-frozen sections from MS cases (n=11) and controls
      (n=6). Data on 1,443 blood vessels was acquired from active lesions (n=13),
      inactive lesions (n=13), NAWM (n=20) and control white matter (n=13). In MS
      abnormal JAM-A expression was found in active (46%) and inactive lesions (21%),
      comparable to previous data using ZO-1. However, a lower level of TJ abnormality
      was found in MS NAWM using JAM-A (3%) compared to ZO-1 (13%). JAM-B was strongly
      expressed on a small number of large blood vessels in control and MS tissues but
      at too low a level for quantitative analysis. By comparison with the high levels
      of abnormality observed with the TJ proteins, the adherens junction protein beta
      catenin was normally expressed in all MS and control tissue categories. These
      results confirm, by use of the independent marker JAM-A, that TJ abnormalities
      are most frequent in active white matter lesions. Altered expression of JAM-A, in
      addition to affecting junctional tightness may also both reflect and affect
      leukocyte trafficking, with implications for immune status within the diseased
      CNS. Conversely, the adherens junction component of the TJ, as indicated by beta
      catenin expression is normally expressed in all MS and control tissue categories.

PMID- 17024497
TI  - Prostate cancer: comparison of local staging accuracy of pelvic phased-array coil
      alone versus integrated endorectal-pelvic phased-array coils. Local staging
      accuracy of prostate cancer using endorectal coil MR imaging.
AB  - To compare the visibility of anatomical details and prostate cancer local staging
      performance of pelvic phased-array coil and integrated endorectal-pelvic phased
      array coil MR imaging, with histologic analysis serving as the reference
      standard. MR imaging was performed in 81 consecutive patients with biopsy-proved
      prostate cancer, prior to radical prostatectomy, on a 1.5T scanner. T2-weighted
      fast spin echo images of the prostate were obtained using phased-array coil and
      endorectal-pelvic phased-array coils. Prospectively, one radiologist,
      retrospectively, two radiologists and two less experienced radiologists working
      in consensus, evaluated and scored all endorectal-pelvic phased-array imaging,
      with regard to visibility of anatomical details and local staging. Receiver
      operator characteristics (ROC) analysis was performed. Anatomical details of the
      overall prostate were significantly better evaluated using the endorectal-pelvic
      phased-array coil setup (P<0.05). The overall local staging accuracy, sensitivity
      and specificity for the pelvic phased-array coil was 59% (48/81), 56% (20/36) and
      62% (28/45), and for the endorectal-pelvic phased-array coils 83% (67/81), 64%
      (23/36) and 98% (44/45) respectively, for the prospective reader. Accuracy and
      specificity were significantly better with endorectal-pelvic phased-array coils
      (P<0.05). The overall staging accuracy, sensitivity and specificity for the
      retrospective readers were 78-79% (P<0.05), 56-58% and 96%, for the endorectal
      pelvic phased-array coils. Area under the ROC curve (Az) was significantly higher
      for endorectal-pelvic phased-array coils (Az=0.74) compared to pelvic phased
      array coil (Az=0.57), for the prospective reader. The use of endorectal-pelvic
      phased array coils resulted in significant improvement of anatomic details,
      extracapsular extension accuracy and specificity. Overstaging is reduced
      significantly with equal sensitivity when an endorectal-pelvic phased-array coil
      is used.

PMID- 17024498
TI  - Inhalation of diluted diesel engine emission impacts heart rate variability and
      arrhythmia occurrence in a rat model of chronic ischemic heart failure.
AB  - Both increase in cardiac arrhythmia incidence and decrease in heart rate
      variability (HRV) have been described following human and experimental animal
      exposures to air pollutants. However, the potential causal relationship between
      these two factors remains unclear. Incidence of ventricular arrhythmia and HRV
      were evaluated during and after a 3 h period of Diesel engine exhaust exposure in
      ten healthy and ten chronic ischemic heart failure (CHF, 3 months after coronary
      ligation) Wistar rats using implantable ECG telemetry. Air pollutants were
      delivered to specifically designed whole body individual exposure chambers at
      particulate matter concentrations similar to those measured inside cabins of cars
      inserted in congested urban traffic. Recordings were obtained from unrestrained
      and unsedated vigil rats. Immediate decrease in RMSSD was observed in both
      healthy (6.64 +/- 2.62 vs. 4.89 +/- 1.67 ms, P < 0.05) and CHF rats (8.01 +/-
      0.89 vs. 6.6 +/- 1.37 ms, P < 0.05) following exposure. An immediate 200-500%
      increase in ventricular premature beats was observed in CHF rats only. Whereas
      HRV progressively returned to baseline values within 2.5 h after exposure start,
      the proarrhythmic effect persisted as late as 5 h after exposure termination in
      CHF rats. Persistence of ventricular proarrhythmic effects after HRV
      normalization suggests that HRV reduction is not the mechanism of cardiac
      arrhythmias in this model. Our methodological approach, closely reflecting the
      real clinical situations, appeared to be a unique tool to provide further insight
      into the pathophysiological mechanisms of traffic related airborne pollution
      health impact.

PMID- 17024499
TI  - Hearing and frequency dependence of auditory interneurons in the parasitoid fly
      Homotrixa alleni (Tachinidae: Ormiini).
AB  - The parasitoid tachinid fly Homotrixa alleni detects its hosts by their acoustic
      signals. The tympanal organ of the fly is located at the prothorax and contains
      scolopidial sensory units of different size and orientation. The tympanal
      membrane vibrates in the frequency range of approximately 4-35 kHz, which is also
      reflected in the hearing threshold measured at the neck connective. The auditory
      organ is not tuned to the peak frequency (5 kHz) of the main host, the bush
      cricket Sciarasaga quadrata. Auditory afferents project in the three thoracic
      neuromeres. Most of the ascending interneurons branch in all thoracic neuromeres
      and terminate in the deutocerebrum of the brain. The interneurons do not differ
      considerably in frequency tuning, but in their sensitivity with lowest thresholds
      around 30 dB SPL. Suprathreshold responses of most neurons depend on frequency
      and intensity, indicating inhibitory influence at higher intensities. Some
      neurons respond particularly well at low frequency sounds (around 5 kHz) and high
      intensities (80-90 dB SPL), and thus may be involved in detection of the primary
      host, S. quadrata. The auditory system of H. alleni contains auditory
      interneurons reacting in a wide range of temporal patterns from strictly phasic
      to tonic and with clear differences in frequency responses.

PMID- 17024500
TI  - Interactive technologies and videotapes for patient education in cancer care:
      systematic review and meta-analysis of randomised trials.
AB  - GOALS OF WORK: Patients diagnosed with cancer need education as they face complex
      decisions. There is limited evidence about the impact of new educational
      technologies for cancer patients. This paper investigates whether interactive
      technologies and videotapes for patient education in cancer care improve
      knowledge, satisfaction or other outcomes. METHODS: Literature search of five
      computerised databases (Medical Literature Analysis and Retrieval System,
      Excerpta Medica Database, Cumulative Index to Nursing and Allied Health
      Literature, Cochrane Controlled Trials Register and Cochrane Database of
      Systematic Reviews) and bibliography searches identified relevant randomized
      controlled trials. Two reviewers independently assessed trial quality. Summary
      effects for knowledge and satisfaction were calculated using random-effects
      models (RevMan 4.2 software). Continuous data were summarised as weighted mean
      differences and dichotomous data as odds ratios, each with their respective 95%
      confidence interval. Standardised effect sizes for these outcomes were calculated
      and contrasted. RESULTS: Nine randomised control trials with 1,678 patients were
      identified. Three evaluated the use of videotapes, and six evaluated computer
      technologies. Studies were of good-quality design but were variable in
      instruments, content, populations, outcomes and results. Educational technologies
      showed improved patient knowledge (effect sizes ranging from 0.12 to 1.03).
      Satisfaction was improved in some studies, but the overall effect was more
      equivocal--effect sizes ranged (0.05 to 0.40) of benefit for knowledge and from 0
      to 0.40 for satisfaction. CONCLUSIONS: The trials present preliminary evaluations
      of the technology in North America, the UK and Australia. There is a trend to
      improved knowledge and satisfaction. The ways in which the interventions are
      delivered and the extent of communication with a health professional affect
      patient responses.

PMID- 17024501
TI  - [Post-operative sclerosing mesenteritis].
AB  - For the first time we describe a sclerosing mesenteritis that appeared acutely
      after abdominal operations. The patient suffered from diffuse abdominal symptoms.
      There was a hard tumour in the left middle and lower abdomen. Histological
      analysis revealed fibrosis and bone tissue. Symptoms improved after application
      of prednisone and high-calorie infusions.

PMID- 17024502
TI  - Is the quantity of circulatory cell-free DNA in human plasma and serum samples
      associated with gender, age and frequency of blood donations?
AB  - Circulatory cell-free DNA (cf-DNA) is increased in a variety of clinical
      pathologic conditions; therefore, these markers could be widely used as markers
      for detecting and monitoring several disorders. To better understand the biology
      of this molecule, we analysed the relationship between the level of circulatory
      cf-DNA and physiological parameters such as gender, age and frequency of blood
      donations. Paired plasma and serum samples were obtained from 87 blood donors and
      50 healthy adults who had never donated blood. Cf-DNA was extracted from plasma
      and serum samples using the MagNA Pure LC Instrument. Quantity determination of
      circulatory cf-DNA was performed by TaqMan real-time PCR for the ubiquitous GAPDH
      gene. Our data showed that the concentration of cf-DNA in serum was about
      eightfold higher than that in plasma. Regarding the level of these circulatory
      species, no significant differences were observed between the age-matched men and
      women and gender-matched, different-age cohorts, except in women who were older
      than 60 years of age. Frequent blood donations did not increase the circulatory
      species. Circulatory cf-DNA in plasma and serum samples is not correlated with
      human gender and human age except in women who are older than 60 years of age.
      Frequent blood donation did not affect the quantity of circulatory cf-DNA. The
      explanation for the latter most likely is the short half-life time of free fetal
      DNA in maternal circulation.

PMID- 17024503
TI  - Delayed maturation of immunoglobulin G avidity: implication for the diagnosis of
      toxoplasmosis in pregnant women.
AB  - The low avidity of immunoglobulin G has been reported to be a useful marker of
      recent infection with Toxoplasma. Several investigators, however, have published
      discrepant result on the maturation of avidity over time. The aim of this study
      was to analyse persistent low avidity of immunoglobulin G in immunocompetent
      individuals and in pregnant women and how it could interfere in the flowchart of
      antenatal diagnosis of toxoplasmosis in the latter group. An international
      literature search was conducted together with a retrospective study of a hospital
      database. Eleven publications that met the inclusion criteria reported delayed
      maturation of avidity at a frequency ranging from 0 to 66.6% of the patients.
      Examination of those publications demonstrated an important heterogeneity in the
      type of assay used, the calculation of avidity, the cutoff above which avidity
      was considered to be elevated, and the delay since infection after which indices
      are expected to be high. In the hospital database, persistent low avidity was
      found even after a median follow-up period of 6 years. Different factors could
      interfere with maturation of avidity, such as variations between individuals, the
      assay system used, and, possibly, the treatment administered. The results of this
      study clearly demonstrate that, in a pregnant woman, an acute infection cannot be
      reliably diagnosed solely on the basis of low avidity of immunoglobulin G.
      Further investigations and standardization of assays are urgently needed.
      Estimation of the time of infection remains difficult, especially in cases in
      which the samples are drawn late in pregnancy; the final estimate must be based
      on several tests repeated at intervals of weeks.

PMID- 17024504
TI  - A new category--healthcare-associated pneumonia: a good idea, but problems with
      its execution.

PMID- 17024505
TI  - Ertapenem versus cefepime for initial empirical treatment of pneumonia acquired
      in skilled-care facilities or in hospitals outside the intensive care unit.
AB  - The study presented here compared the efficacy and safety of ertapenem and
      cefepime as initial treatment for adults with pneumonia acquired in skilled-care
      facilities or in hospital environments outside the intensive care unit (ICU). Non
      ventilated patients developing pneumonia in hospital environments outside the
      ICU, in nursing homes, or in other skilled-care facilities were enrolled in this
      double-blind non-inferiority study, stratified by APACHE II score (<or=15 vs >15)
      and randomized (1:1) to receive cefepime (2 g every 12 h with optional
      metronidazole 500 mg every 12 h) or ertapenem (1 g daily). After 3 days of
      parenteral therapy, participants demonstrating clinical improvement could be
      switched to oral ciprofloxacin or another appropriate oral agent. Probable
      pathogens were identified in 162 (53.5%) of the 303 randomized participants. The
      most common pathogens were Enterobacteriaceae, Streptococcus pneumoniae, and
      Staphylococcus aureus, isolated from 59 (19.5%), 39 (12.9%), and 35 (11.6%)
      participants, respectively. At the test-of-cure assessment 7-14 days after
      completion of all study therapy, pneumonia had resolved or substantially improved
      in 89 (87.3%) of 102 clinically evaluable ertapenem recipients and 80 (86%) of 93
      clinically evaluable cefepime recipients (95% confidence interval for the
      difference, -9.4 to 11.8%), fulfilling pre-specified criteria for statistical non
      inferiority. The frequency and severity of drug-related adverse events were
      generally similar in both treatment groups. In this study population, ertapenem
      was as well-tolerated and efficacious as cefepime for the initial treatment of
      pneumonia acquired in skilled-care facilities or in hospital environments outside
      the ICU.

PMID- 17024506
TI  - Evaluation of a single-locus real-time polymerase chain reaction as a screening
      test for specific detection of methicillin-resistant Staphylococcus aureus in ICU
      patients.
AB  - The aim of the present study was to determine the diagnostic value of a single
      locus real-time polymerase chain reaction (PCR) recently proposed for rapid
      detection of methicillin-resistant Staphylococcus aureus (MRSA) from clinical
      samples (IDI-MRSA; Infectio Diagnostic, Sainte-Foy, Quebec, Canada). This test,
      which was developed on the basis of studies of the sequence analysis of the mecA
      gene carried by staphylococcal cassette chromosome mec (SCCmec), was used to
      screen nasal swabs of 320 intensive care unit (ICU) patients at admission. The
      results were compared with those of conventional culture of swabs from several
      body sites. When compared with culture of swabs from the nose, throat, and
      wounds, the diagnostic values of the real-time PCR test from nasal swabs were as
      follows: 92.3% sensitivity, 98.6% specificity, 75.0% positive predictive value,
      and 99.6% negative predictive value. Fifteen (4.7%) samples could not be
      evaluated because the PCR reaction was inhibited, even after the samples were
      frozen and thawed for retesting. Culture of nasal swabs showed that 78 of the
      patients were colonized with methicillin-susceptible S. aureus. Unexpectedly, 4
      (5.1%) of these samples gave false-positive results in the IDI-MRSA. These
      isolates were all single clones, as shown by pulsed-field gel electrophoresis and
      spa typing. Reliable results were obtained with the IDI-MRSA assay, even in a
      patient population with a low prevalence (approximately 4%) of MRSA and even when
      compared with swabs of different body sites. Nevertheless, further work is needed
      to reduce the inhibition rate of the PCR and to explain why false-positive
      results were obtained with methicillin-susceptible S. aureus.

PMID- 17024507
TI  - Detection of imported histoplasmosis in serum of HIV-infected patients using a
      real-time PCR-based assay.
AB  - A new real-time PCR-based assay was used for detecting DNA of Histoplasma
      capsulatum in serum samples collected from four HIV-infected patients with proven
      histoplasmosis. The assay targeted the ITS1 region of rDNA and its in vitro
      sensitivity, specificity and reproducibility were evaluated. The technique
      detected DNA of H. capsulatum in all of the HIV-infected patients with proven
      histoplasmosis (4/4, 100%). The PCR result was positive for seven of the ten
      (70%) samples studied. The assay's specificity was determined to be 100%, since
      the method was negative for 25 other serum samples (10 from patients with proven
      aspergillosis and 15 from healthy controls). The PCR assay is a new and promising
      diagnostic alternative and further investigation is warranted.

PMID- 17024508
TI  - Towards a "virtual pigeon": a new technique for investigating avian social
      perception.
AB  - The purpose of the present study is to examine the applicability of a computer
      generated, virtual animal to study animal cognition. Pigeons were trained to
      discriminate between movies of a real pigeon and a rat. Then, they were tested
      with movies of the computer-generated (CG) pigeon. Subjects showed generalization
      to the CG pigeon, however, they also responded to modified versions in which the
      CG pigeon was showing impossible movement, namely hopping and walking without its
      head bobbing. Hence, the pigeons did not attend to these particular details of
      the display. When they were trained to discriminate between the normal and the
      modified version of the CG pigeon, they were able to learn the discrimination.
      The results of an additional partial occlusion test suggest that the subjects
      used head movement as a cue for the usual vs. unusual CG pigeon discrimination.

PMID- 17024509
TI  - A New Caledonian crow (Corvus moneduloides) creatively re-designs tools by
      bending or unbending aluminium strips.
AB  - Previous observations of a New Caledonian crow (Corvus moneduloides)
      spontaneously bending wire and using it as a hook [Weir et al. (2002) Science
      297:981] have prompted questions about the extent to which these animals
      'understand' the physical causality involved in how hooks work and how to make
      them. To approach this issue we examine how the same subject ("Betty") performed
      in three experiments with novel material, which needed to be either bent or
      unbent in order to function to retrieve food. These tasks exclude the possibility
      of success by repetition of patterns of movement similar to those employed
      before. Betty quickly developed novel techniques to bend the material, and
      appropriately modified it on four of five trials when unbending was required. She
      did not mechanically apply a previously learned set of movements to the new
      situations, and instead sought new solutions to each problem. However, the
      details of her behaviour preclude concluding definitely that she understood and
      planned her actions: in some cases she probed with the unmodified tools before
      modifying them, or attempted to use the unmodified (unsuitable) end of the tool
      after modification. Gauging New Caledonian crows' level of understanding is not
      yet possible, but the observed behaviour is consistent with a partial
      understanding of physical tasks at a level that exceeds that previously attained
      by any other non-human subject, including apes.

PMID- 17024510
TI  - Imitation: definitions, evidence, and mechanisms.
AB  - Imitation can be defined as the copying of behavior. To a biologist, interest in
      imitation is focused on its adaptive value for the survival of the organism, but
      to a psychologist, the mechanisms responsible for imitation are the most
      interesting. For psychologists, the most important cases of imitation are those
      that involve demonstrated behavior that the imitator cannot see when it performs
      the behavior (e.g., scratching one's head). Such examples of imitation are
      sometimes referred to as opaque imitation because they are difficult to account
      for without positing cognitive mechanisms, such as perspective taking, that most
      animals have not been acknowledged to have. The present review first identifies
      various forms of social influence and social learning that do not qualify as
      opaque imitation, including species-typical mechanisms (e.g., mimicry and
      contagion), motivational mechanisms (e.g., social facilitation, incentive
      motivation, transfer of fear), attentional mechanisms (e.g., local enhancement,
      stimulus enhancement), imprinting, following, observational conditioning, and
      learning how the environment works (affordance learning). It then presents
      evidence for different forms of opaque imitation in animals, and identifies
      characteristics of human imitation that have been proposed to distinguish it from
      animal imitation. Finally, it examines the role played in opaque imitation by
      demonstrator reinforcement and observer motivation. Although accounts of
      imitation have been proposed that vary in their level of analysis from neural to
      cognitive, at present no theory of imitation appears to be adequate to account
      for the varied results that have been found.

PMID- 17024511
TI  - Reproducing human actions and action sequences: "Do as I Do!" in a dog.
AB  - We present evidence that a dog (Philip, a 4-year-old tervueren) was able to use
      different human actions as samples against which to match his own behaviour.
      First, Philip was trained to repeat nine human-demonstrated actions on command
      ('Do it!'). When his performance was markedly over chance in response to
      demonstration by one person, testing with untrained action sequences and other
      demonstrators showed some ability to generalise his understanding of copying. In
      a second study, we presented Philip with a sequence of human actions, again using
      the 'Do as I do' paradigm. All demonstrated actions had basically the same
      structure: the owner picked up a bottle from one of six places; transferred it to
      one of the five other places and then commanded the dog ('Do it!'). We found that
      Philip duplicated the entire sequence of moving a specific object from one
      particular place to another more often than expected by chance. Although results
      point to significant limitations in his imitative abilities, it seems that the
      dog could have recognized the action sequence, on the basis of observation alone,
      in terms of the initial state, the means, and the goal. This suggests that dogs
      might acquire abilities by observation that enhance their success in complex
      socio-behavioural situations.

PMID- 17024512
TI  - Non-reproductive copulation behavior among Tibetan macaques (Macaca thibetana) at
      Huangshan, China.
AB  - Non-reproductive copulation, which takes place outside of the mating season and
      does not result in conception and birth, was studied in a free-ranging group of
      Tibetan monkeys (Macaca thibetana) at Mt. Huangshan, China, in the birth seasons
      of 1992 and 1997. We employed all occurrence and focal animal samplings to record
      sexual and related behaviors and affiliation interactions, respectively. Compared
      with sexual behavior in mating season, non-reproductive copulation occurred at a
      lower frequency, with less frequent ejaculation, less harassment, shorter mount
      duration, and an absence of pause with vocalization. It often took place in a
      situation in which non-lactating females were involved in social conflict or
      approached males for mating. Neither pregnant nor lactating females were observed
      to mate in the birth seasons. Copulation during the birth season did not increase
      a sexually receptive female's delivery the next year, nor was it associated with
      increased proximity, grooming, or agonistic aid for the mating pair. However,
      copulated pairs spent more time co-feeding, presumably reflecting an increased
      tolerance on the part of the male. Adolescent males, who rarely copulated in the
      mating season, engaged in mating activity in birth seasons as well. Therefore,
      though birth-season copulation had no reproductive functions, it may have
      fulfilled social functions for females, such as post-aggression appeasing by
      males or gaining access to resources. This also offered good opportunities for
      adolescent males and females to develop their sexual skills for later
      competition.

PMID- 17024513
TI  - Comparative analysis of estrogen receptor gene polymorphisms in apes.
AB  - Polymorphic microsatellite repeats in the promoter region of estrogen receptor
      alpha gene (ESRalpha and the intron 6 region of estrogen receptor beta gene
      (ESRbeta) have been reported in human populations. To examine the evolutional
      state of both repeats, we surveyed the corresponding regions in DNA sequences
      from the following great apes and gibbons: 56 chimpanzees, 3 bonobos, 16
      gorillas, 20 orangutans and 60 gibbons (four species: 17 of Hylobates agilis, 11
      of H. lar, 15 of H. muelleri, and 17 of H. syndactylus). In the corresponding
      region of the TA repeat of human ESRalpha, chimpanzees and bonobos had two motifs
      in the repeat tract, (TA)(7-9) and (CA)(4-6). Gorillas had the (TA)(9-10) repeat
      tracts and orangutans had monomorphic (TA)(7) repeats. Although all great apes
      maintained the TA expansion, all gibbon sequences contained (TA)(2), implying
      that the CA dinucleotide expansion arose in the ancestor of chimpanzees and
      bonobos. The nucleotide sequences of ESRbeta showed a very complex repeat pattern
      in apes. The human sequences had a non-variable preceding sequence at (CA)(n),
      (GA)(2)(TA)(8)(CA)(4)(TA). In apes that region included {(TA)(n)(CA)(n)}(n).
      Gibbon sequences included (TATG)(n) and (TATC)(n) and no regular construction was
      observed. A deletion event in the reverse primer site seems to have occurred in
      the orangutan lineage. In addition, a great diversity of allele length was
      detected in each gibbon species.

PMID- 17024514
TI  - The breeding system of wild red ruffed lemurs (Varecia rubra): a preliminary
      report.
AB  - Captive studies have shown that ruffed lemurs (Varecia) have an unusual suite of
      reproductive traits combined with extremely high maternal reproductive costs.
      These traits include the bearing of litters, nesting of altricial young, and
      absentee parenting. To characterize the breeding system of this enigmatic lemur,
      reproductive traits must be contextualized in the wild. Here, I provide a
      preliminary report of mating and infant care in one community of wild red ruffed
      lemurs (Varecia rubra). Observations span a 15-month period covering two birth
      seasons and one mating season on the Masoala Peninsula, Madagascar. Factors that
      are not possible to replicate in captivity are reported, such as mating pattern,
      natality and mortality rates, the location of nests within the home range, and
      the structuring of infant care within a natural community. V. rubra at Andranobe
      have a fission-fusion, multifemale-multimale grouping pattern and a polygamous
      mating system. They do not mate monogamously or live strictly in family-based
      groups as suggested by previous workers. During the first 2 months of life, nests
      and infant stashing localities are situated within each mother's respective core
      area, and inhabitants of each core area within the communal home range provide
      care for young. As part of their absentee parenting system, infants are left in
      concealed, protected, and supportive spots high in the canopy, while mothers
      travel distantly. This practice is termed 'infant stashing'. Alloparenting
      appears to be an integral part of V. rubra's overall reproductive strategy in the
      wild, as it was performed by all age-sex classes. Among the alloparental
      behaviors observed were infant guarding, co-stashing, infant transport, and
      allonursing. Alloparenting and absentee parenting may mitigate high maternal
      reproductive costs. Furthermore, V. rubra may have a breeding system in which
      genetic partners (i.e., mating partners) do not always correspond to infant care
      providers. Combined with recently available information on the behavioral ecology
      of wild ruffed lemurs, this preliminary report suggests directions for in-depth
      studies on Varecia's breeding system.

PMID- 17024516
TI  - Composition of archaeal, bacterial, and eukaryal RuBisCO genotypes in three
      Western Pacific arc hydrothermal vent systems.
AB  - We studied the diversity of all forms of the RuBisCO large subunit-encoding gene
      cbbL in three RuBisCO uncharacterized hydrothermal vent communities. This
      diversity included the archaeal cbbL and the forms IC and ID, which have not
      previously been studied in the deep-sea environment, in addition to the forms IA,
      IB and II. Vent plume sites were Fryer and Pika in the Mariana arc and the Suiyo
      Seamount, Izu-Bonin, Japan. The cbbL forms were PCR amplified from plume bulk
      microbial DNA and then cloned and sequenced. Archaeal cbbL was detected in the
      Mariana samples only. Both forms IA and II were amplified from all samples, while
      the form IC was amplified only from the Pika and Suiyo samples. Only the Suiyo
      sample showed amplification of the form ID. The form IB was not recorded in any
      sample. Based on rarefaction analysis, nucleotide diversity and average pairwise
      difference, the archaeal cbbL was the most diverse form in Mariana samples, while
      the bacterial form IA was the most diverse form in the Suiyo sample. Also, the
      Pika sample harbored the highest diversity of cbbL phylogenetic lineages. Based
      on pairwise reciprocal library comparisons, the Fryer and Pika archaeal cbbL
      libraries showed the most significant difference, while Pika and Suiyo showed the
      highest similarity for forms IA and II libraries. This suggested that the Fryer
      supported the most divergent sequences. All archaeal cbbL sequences formed unique
      phylogenetic lineages within the branches of anaerobic thermophilic archaea of
      the genera Pyrococcus, Archaeoglobus, and Methanococcus. The other cbbL forms
      formed novel phylogenetic clusters distinct from any recorded previously in other
      deep-sea habitats. This is the first evidence for the diversity of archaeal cbbL
      in environmental samples.

PMID- 17024517
TI  - Physiological implications of metabolite biosynthesis for net assimilation and
      heat-stress tolerance of sugarcane (Saccharum officinarum) sprouts.
AB  - Global increase in ambient temperature is a critical factor for plant growth. In
      order to study the changes in growth over short intervals, various primary and
      secondary metabolites, and their relationships with thermotolerance, 1-month-old
      sugarcane (Saccharum officinarum) sprouts were grown under control conditions (28
      degrees C) or under heat-stress conditions (40 degrees C), and measurements were
      made at six 12-h intervals. Heat stress greatly reduced dry matter and leaf area
      of sprouts initially but only nominally later on. Changes in the rates of
      relative growth and net assimilation were greater than relative leaf expansion,
      indicating an adverse effect of heat on assimilation of nutrients and CO(2) in
      producing dry matter. Although reduction in leaf water potential was an immediate
      response to heat, this effect was offset by early synthesis of free proline,
      glycinebetaine and soluble sugars (primary metabolites). Among secondary
      metabolites, anthocyanin synthesis was similar to primary metabolites;
      carotenoids and soluble phenolics accumulated later while chlorophyll remained
      unaffected. Relationships of growth attributes and metabolite levels, not seen in
      the controls, were evident under heat stress. In summary, observed changes in
      metabolite levels were spread over time and space and were crucial in improving
      net assimilation and heat tolerance of sugarcane.

PMID- 17024518
TI  - Perineal cellulitis as a late complication of trans-obturator sub-urethral tape,
      Obtape.
AB  - The authors report the case of a perineal cellulitis occurring 10 months after
      the surgical treatment for stress urinary incontinence with a trans-obturator sub
      urethral tape, Obtape (Porges). This is a very rare complication related to a
      prolonged intra-vaginal tape exposure and infection that occurs after vaginal
      erosion, possibly due to tape rejection. This complication has been described
      with Obtape and with Uratape. The former lacks a sub-urethral silicone coated
      section that distinguishes it from Uratape. We still do not know much about the
      constituents of these types of sub-urethral tapes specially about their human
      tolerance, and we should therefore look at them carefully.

PMID- 17024520
TI  - Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal
      women.
AB  - The aim of this study was to explore the relationship between biomechanical
      properties and the occurrence of pelvic organ prolapse (POP) through analysis on
      biomechanical properties of vaginal tissue. The biopsy specimens were obtained
      from 43 patients undergoing transvaginal hysterectomy, who were assigned into
      premenopausal POP, postmenopausal POP, premenopausal control and postmenopausal
      control groups. Tissue specimens were biomechanically assessed by a purpose-built
      tissue puller system, and stress-strain curves were digitally recorded. The
      Young's modulus, Poisson's ratio, maximum elongation, maximum fracture of vaginal
      tissue were 9.45 +/- 0.70, 0.43 +/- 0.01, 1.50 +/- 0.02, 0.60 +/- 0.02 in
      premenopausal POP group; 12.10 +/- 1.10, 0.39 +/- 0.01, 1.14 +/- 0.05, 0.27 +/-
      0.03 in postmenopausal POP group; 6.65 +/- 1.48, 0.46 +/- 0.01, 1.68 +/- 0.11,
      0.79 +/- 0.05 in premenopausal control group and 10.26 +/- 1.10, 0.42 +/- 0.01,
      1.37 +/- 0.04, 0.42 +/- 0.03 in postmenopausal control group. There was
      significant difference in biomechanical properties between premenopausal POP
      group and premenopausal control group (p < 0.01). There was significant
      difference in biomechanical properties between postmenopausal POP group and
      postmenopausal control group (p < 0.01). Biomechanical properties in POP group
      were significantly lower than that in control group, suggesting that degeneration
      of biomechanical properties in pelvic support construction might lead to the
      occurrence of POP.

PMID- 17024519
TI  - Of porcupines and poodles--a joint challenge to industry and the profession.

PMID- 17024521
TI  - Cecal perforation complicating placement of a transvaginal tension-free vaginal
      tape.
AB  - The tension-free vaginal tape has been increasingly used to treat stress urinary
      incontinence. This procedure has a high success rate and unique surgical
      complications. The patient is a 39-year-old with genuine stress urinary
      incontinence and underwent placement of tension-free vaginal tape for treatment.
      Twelve hours after the procedure, the patient had increasing abdominal pain, and
      an acute abdominal series showed free intraperitoneal air. Exploratory laparotomy
      revealed stool in the peritoneal cavity, with the vaginal tape placed through the
      cecum. Bowel complications are rare; however, they may occur and should be
      suspected in a patient with an acute abdomen and free air.

PMID- 17024522
TI  - Evaluation of the use of CD-ROM upload into the PACS or institutional web server.
AB  - PURPOSE: Patient data are increasingly distributed between hospitals using CD
      ROMs instead of actual films. This introduces problems because different viewers
      from different vendors are provided, and sometimes viewers are unusable because
      local software installation is not allowed. In 2004, we started to facilitate the
      incorporation of CD-ROM data into the normal workflow of the hospital by using
      commercially available software to perform patient reconciliation based on the
      DICOM (digital imaging and communication in medicine) modality worklist. The
      purpose of the current study is to evaluate this new procedure. METHODS AND
      MATERIALS: A questionnaire was sent to all users to evaluate the satisfaction
      with the current facility and to evaluate possible improvements. Several quality
      parameters on speed and satisfaction were rated on a 5-point scale (1 = bad to 5
      = excellent). RESULTS: Replies from 17 different respondents were evaluated,
      accounting for an average of 76 CD-ROMs per week. Mean (median) results showed a
      score of 3.6 (4) for handling time, 3.4 (4) for archival of second opinion data,
      3.8 (median 4) for archival of external data onto the web server, and 4.5 (median
      5) for the overall performance of the current procedure. CONCLUSION: Although
      some improvements can be made, storage of the study data from CDs from
      outpatients into PACS (picture archiving and communication system) and web server
      already provides for an existing need. Using this service, physicians can access
      the data with ease and familiarity. User satisfaction with the provided solution
      is high.

PMID- 17024523
TI  - The mammalian 2'-5' oligoadenylate synthetase gene family: evidence for concerted
      evolution of paralogous Oas1 genes in Rodentia and Artiodactyla.
AB  - Multiple 2'-5' oligoadenylate (2-5A) synthetases are important components of
      innate immunity in mammals. Gene families encoding these proteins have previously
      been studied mainly in humans and mice. To reconstruct the evolution of this gene
      family in mammals, a search for additional 2-5A synthetase genes was performed in
      rat, cattle, pig, and dog. Twelve 2'-5' oligoadenylate synthetase (Oas) genes
      were identified in the rat genome, including eight Oas1 genes, two Oas1
      pseudogenes, single copies of Oas2 and Oas3, and two Oas-like genes, Oasl1 and
      Oasl2. Four OAS genes were detected in the pig genome and five OAS genes were
      found in both the cattle and dog genomes. An OAS3 gene was not found in either
      the cattle or the pig genome. While two tandemly duplicated OAS-like (OASL) genes
      were identified in the dog genome, only a single OASL orthologue was found in
      both the cattle and the pig genomes. The bovine and porcine OASL genes contain
      premature stop codons and encode truncated proteins, which lack the typical C
      terminal double ubiquitin domains. The cDNA sequences of the rat, cattle, pig,
      and dog OAS genes were amplified, sequenced and compared with each other and with
      those in the human, mouse, horse, and chicken genomes. Evidence of concerted
      evolution of paralogous 2'-5' oligoadenylate synthetase 1 genes was obtained in
      rodents (Rodentia) and even-toed ungulates (Artiodactyla). Calculations using the
      nonparametric Kolmogorov-Smirnov test suggested that the homogenization of
      paralogous OAS1 sequences was due to gene conversion rather than stabilizing
      selection.

PMID- 17024524
TI  - Sex-biased gene expression in a ZW sex determination system.
AB  - Studies of the transcriptome have shown that a substantial fraction of
      interspecific differences in gene expression is the result of sex-biased gene
      expression. These results suggest that sex-dependent selection may be an
      important force in generating differences between species but to date all studies
      have focused on Drosophila. We examined a sample of the transcriptome in the
      gonads of two species of Xenopus to provide an additional test of how sex-biased
      gene expression may contribute to differences in gene expression between species.
      In contrast to Drosophila, Xenopus provides an example of a ZW system with
      morphologically indistinguishable sex chromosomes. About 81% of the transcriptome
      was differentially expressed between X. laevis and X. muelleri and there were
      more genes that were male-biased compared to the number of genes that were female
      biased or non-sex-biased. While there were more genes up-regulated in males of
      Xenopus, the largest magnitude difference in expression between species occurred
      in female-biased genes, and male-biased genes were proportionally more abundant
      for the smallest changes in expression between species. Our results suggest that
      more genes have a role in the function of the testis compared to the ovary and
      female-biased genes play a principle role in expression divergence between
      species. These results differ from those in the Drosophila XY system in that more
      female-biased genes had >4-fold difference of expression between species than
      male-biased genes, suggesting that ZW sex chromosomes may facilitate enhanced
      gene expression divergence between species.

PMID- 17024525
TI  - Early versus delayed-interval laparoscopic cholecystectomy for acute
      cholecystitis: a metaanalysis.

PMID- 17024527
TI  - Peroral endoscopic reduction of dilated gastrojejunal anastomosis after Roux-en-Y
      gastric bypass: a possible new option for patients with weight regain.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective treatment for severe
      obesity. However, many patients regain weight over time. The mechanisms for this
      are unclear, and several factors may contribute, including dilation of the
      gastrojejunal anastomosis. This study aimed to assess the feasibility of
      endoscopic gastrojejunal anastomotic tightening and to determine the effect of
      tightening on body weight. METHODS: Eight patients with significant weight regain
      and dilated gastrojejunal anastomosis after RYGB were included in this pilot
      study. Sutures were placed endoscopically at the rim of the anastomosis. When
      tightened, the sutures formed tissue placations, reducing the size of the
      anastomotic aperture. RESULTS: The average preprocedure body mass index (BMI) was
      40.5, and the patients had regained a mean of 24 kg from their post-RYGB nadir.
      The average pouch length was 5.7 cm, and the average anastomotic diameter was 25
      mm. The average postreduction diameter was 10.0 mm (68% reduction). Six of the
      eight patients showed weight loss (mean, 10 kg) at 4 months. Repeat procedures
      were performed for three patients who had lost 4, 5, and 9 kg, respectively with
      the initial procedure. After the second anastomotic reduction, the final
      diameters were, respectively, 14, 5, and 5 mm. The first patient did not have
      further weight loss. The remaining two patients showed a total weight loss of 19
      and 20 kg, respectively, at 5 months. All 11 reductions were accomplished without
      significant complication. The average postreduction BMI was 37.7, and the
      percentage of excess weight loss was 23.4%. CONCLUSION: Peroral endoscopic
      suturing to tighten dilated gastrojejunal anastomoses appears technically
      feasible and safe. This procedure is associated with variable but significant
      weight loss, and preliminary results suggest that it may offer a new treatment
      option for postbypass weight regain in selected patients.

PMID- 17024526
TI  - Laparoscopic vs conventional tension free inguinal herniorrhaphy: 2005 society of
      American Gastrointestinal Endoscopic Surgeons (SAGES) annual meeting debate.
AB  - This report summarizes the 2005 Society of American Gastrointestinal and
      Endoscopic Surgeons' inguinal herniorrhaphy debate. Most inguinal herniorrhaphies
      in the United States are performed using one of several prosthesis-based, tension
      free (TFR) procedures. Approximately 15% of the procedures used are laparoscopic
      inguinal herniorrhaphies (LIH). Technical ease, lower cost, and local anesthesia
      are the major advantages attributed to TFR, whereas superior cosmesis, less
      perioperative pain, and a faster return to normal activity is attributed to LIH.
      The overall cost-benefit ratio, incidence of chronic pain syndromes, and
      relevance of a recent major trial could not be entirely settled in this debate.
      The importance of adequate training for surgeons undertaking LIH cannot be
      overemphasized. Experienced surgeons displaying equivalent results for LIH and
      TFR are justified in offering LIH to patients with primary unilateral inguinal
      hernias.

PMID- 17024528
TI  - Technique and assessment of sentinel lymph node biopsy usefulness in laparoscopy
      assisted distal gastrectomy.
AB  - BACKGROUND: Recently, some studies have suggested that sentinel node biopsy also
      can be applied to gastric cancer. The authors apply sentinel lymph node biopsy in
      laparoscopy assisted distal gastrectomy to perform it as safe limited surgery.
      Limited surgery is a procedure in which the extent of lesion resection and lymph
      node dissection is reduced. The authors demonstrate that intraoperative diagnosis
      of lymph node metastasis is useful in this respect. METHODS: The study was
      conducted with 38 patients (29 men and 9 women) who had a preoperative diagnosis
      of T1 tumor invasion. The patients had a mean age of 66.2 years. Patent blue (1%)
      was injected submucosally into four or five different sites around the primary
      tumor at 1 ml per site. Blue-stained lymphatics and lymph nodes could be seen by
      turning over the greater omentum and the lesser omentum extraperitoneally. If
      blue nodes were found, biopsy was performed. RESULTS: The mean number of blue
      nodes dissected was 2.5 +/- 1.9. Intraoperative identification and biopsy of blue
      nodes could be performed for 35 (92.1%) of the 38 patients. Of the 35 patients in
      whom blue nodes were identified, 4 (9.7%) had metastases in blue nodes confirmed
      by intraoperative frozen-section diagnosis. Intraoperative frozen-section
      diagnosis was negative for blue node metastasis in 31 patients. Postoperative
      permanent section diagnosis also showed no evidence of lymph node metastasis in
      these 31 patients (100% accuracy, 0% false-negative rates). CONCLUSION: The
      reported method allows observation of blue-stained lymphatics up to 2 h after
      patent blue injection. Sentinel node biopsy was performed in laparoscopy assisted
      distal gastrectomy, making it technically equivalent to open gastrectomy.
      Sentinel node biopsy can serve as a method to determine the appropriate use of
      laparoscopy assisted distal gastrectomy for management of T1 gastric cancer.

PMID- 17024529
TI  - Comparison of laparoscopically assisted and open radical distal gastrectomy with
      extended lymphadenectomy for gastric cancer management.
AB  - BACKGROUND: The feasibility and safety of laparoscopically assisted gastrectomy
      with extended lymphadenectomy for advanced gastric cancer has rarely been
      studied. This study aimed to investigate the feasibility, safety, and cancer
      clearance of laparoscopically assisted distal gastrectomy with D2
      lymphadenectomy. METHODS: Of the 44 patients with distal gastric cancer who
      underwent radical distal gastrectomy from March 2004 to May 2005, 35 were treated
      with D2/D2(+) lymphadenectomy. These patients were compared with 58 patients who,
      during the same period, underwent a conventional open radical distal gastrectomy.
      RESULTS: The mean total number of retrieved lymph nodes (30.11 +/- 16.97) and the
      mean tumor margin were comparable with those in the open group. The mean
      operative time for laparoscopically assisted distal gastrectomy was significantly
      longer than for open surgery (282.84 +/- 32.81 min vs 223.75 +/- 23.25 min). The
      patients in the laparoscopic surgery group had less blood loss, shorter times of
      analgesic injection, and a faster recovery. The rates of complications were
      comparable between two groups. CONCLUSIONS: Although laparoscopically assisted
      radical gastrectomy with D2 lymphadenectomy is more time consuming than open
      surgery, it is a safe, feasible procedure that achieves cancer clearance similar
      to open surgery and leads to a quick postoperative recovery.

PMID- 17024531
TI  - A laparoscopic approach to partial splenectomy for children with hereditary
      spherocytosis.
AB  - BACKGROUND: Partial splenectomy is sometimes used for children with hereditary
      spherocytosis (HS) to reduce hemolysis while retaining some splenic immune
      function. Previous reports have described a partial splenic resection through a
      laparotomy incision. Whereas laparoscopic total splenectomy for HS is well
      established, laparoscopic partial splenectomy (LPS) has not been described. The
      authors have developed a novel LPS technique that combines the benefits of
      partial splenectomy with those of a laparoscopic approach. METHODS: A chart
      review was conducted for three children with HS who underwent LPS, with
      approximately one-fourth of the spleen left on the basis of the short gastric
      arterial supply. RESULTS: The mean preoperative spleen size was 17.6 cm. The mean
      preoperative hemoglobin count was 100 g/l, and the postoperative hemoglobin count
      was 133 g/l. All three patients reported reduced malaise and increased energy
      levels. There was no recurrent anemia at the 1- to 2-year follow-up evaluation.
      CONCLUSION: The LPS procedure is a safe and effective approach to HS that
      resolves anemia, potentially retains some splenic immunity, and confers the
      benefits of a minimal access technique.

PMID- 17024532
TI  - Laparoscopically assisted reversal of Hartmann's procedure.
AB  - BACKGROUND: Restoration of bowel continuity after Hartmann's procedure is a major
      surgical procedure associated with substantial morbidity and occasional
      mortality. The authors review their experience with laparoscopically assisted
      reversal of Hartmann's procedure (LARH) to assess difficulties and potential
      advantages associated with this procedure. METHODS: A retrospective chart review
      of a prospectively entered database was performed to identify patients who
      underwent LARH over a period of 7 years. Data regarding demographic and clinical
      characteristics, surgical details, and postoperative course were reviewed.
      Specifically, age, gender, diagnosis at initial operation, American Society of
      Anesthesiology (ASA) score, comorbidities, operative time, conversion, surgical
      team, complications, postoperative bowel movements, and hospital stay were
      assessed. All surgeries were performed by six experienced laparoscopic surgeons.
      RESULTS: A total of 27 patients, 17 men and 10 women, with mean ages of 58.1 and
      62.9 years, respectively, underwent LARH. The procedure was laparoscopically
      completed for 23 patients. Conversion to laparotomy was required for four
      patients (14.8%) because of dense adhesions after the initial Hartmann's
      procedure in three patients and rectal perforation in one patient. The median
      operative time was 226 min, and the median hospital stay was 6 days. The overall
      morbidity rate was 33% (9 patients), attributable to colostomy site infection in
      5 of the 9 patients. One patient required reoperation because of intraabdominal
      bleeding. No anastomotic leaks or intraabdominal abscesses were recorded. There
      was no operative mortality. CONCLUSIONS: Laparoscopically assisted reversal of
      Hartmann's procedure is technically challenging and time consuming. However, in
      the hands of experienced laparoscopic surgeons, it is safe and associated with a
      reasonably low conversion rate. Furthermore, the relatively low morbidity rate,
      short hospital stay, and earlier return of bowel function may be beneficial to
      patients.

PMID- 17024533
TI  - Distal pancreas surgery: outcome for 19 cases managed with a laparoscopic
      approach.
AB  - BACKGROUND: In the past decade, laparoscopy has shown its efficacy also for
      advanced surgery. In this report, the authors retrospectively review their
      experience with the distal pancreas. METHODS: From April 1999 to October 2004, 19
      patients underwent a laparoscopic procedure for pathologies of the distal
      pancreas. The authors performed one distal pancreatectomy (DP) with conservation
      of the spleen and section of the splenic vessels, four distal
      splenopancreatectomies (DSP), one DSP plus a left adrenalectomy, two
      enucleations, seven DPs with conservation of the spleen and the splenic vessels,
      and four cystojejunostomies. RESULTS: One procedure was converted to open surgery
      because of a hemorrhagic complication. No other significant intraoperative
      complications occurred. The postoperative course was characterized by one bleed
      managed conservatively, two pancreatic fistulas (one requiring a second
      operation), one abscess drained under echographic view, and one reactive
      pancreatitis. The mean postoperative stay was 8.5 days. The histologic report
      showed 16 benign diseases and 3 malignant tumors. The mean follow-up period was
      of 42 months. The patient who had DP spleen preservation with section of the
      splenic vessels reported mild pain in the left hypochondrium, probably
      attributable to chronic splenic ischemia, during the first 3 postoperative
      months. One incisional hernia occurred in the patient who underwent conversion to
      an open procedure, and one patient affected by adenocarcinoma died 10 months
      after the operation. CONCLUSIONS: The authors can affirm that laparoscopy for the
      distal pancreas is a successful procedure in terms of results and surgical
      feasibility. Prospective studies are necessary to confirm their positive
      impression.

PMID- 17024534
TI  - The importance of classification in sympathetic surgery and a proposed mechanism
      for compensatory hyperhidrosis: experience with 464 cases.
AB  - BACKGROUND: Compensatory hyperhidrosis is the most troublesome side effect and
      the leading cause of regret with sympathetic surgery. A new classification is
      proposed to make the procedure more selective and to minimize the side effects
      and regret rate. Also, a proposed mechanism for compensatory hyperhidrosis is
      discussed. METHODS: Between January 2002 and July 2003, 464 patients with various
      sympathetic disorders underwent thoracoscopic sympathectomy/sympathicotomy (ETS)
      or sympathetic block by clipping (ESB) at various levels according to the
      authors' classification. The surgery was performed on an outpatient basis. The
      rates of success, compensatory hyperhidrosis, and regret were recorded. RESULTS:
      All the patients were followed up for 17 to 35 months. All excessive sweating was
      effectively stopped to varying degrees. The 25 patients with palmar hyperhidrosis
      who insisted on receiving ETS of T4 experienced no compensatory hyperhidrosis. Of
      the 54 patients with facial blushing who received ESB of T2, 23 experienced
      compensatory hyperhidrosis. Nine patients expressed regret and requested removal
      of the clips. Of the 33 patients with craniofacial hyperhidrosis who received ESB
      of T3, 9 experienced compensatory hyperhidrosis. Three expressed regret, and
      reverse procedures were performed. For 324 patients with palmar hyperhidrosis
      receiving ESB of T4, no compensatory hyperhidrosis was found. Only two expressed
      regret because of discomfort. No compensatory hyperhidrosis or regret was noted
      with 28 patients who received ESB of T5 for axillary sweating. There was no
      recurrence in the entire series. CONCLUSIONS: Different procedures are
      recommended for different sympathetic disorders according to the classification.
      The higher the level of sympathetic ganglion blockade, the higher is the regret
      rate. Therefore, for T2 and T3 ganglion, endoscopic thoracic sympathetic block by
      the clipping method is strongly recommended because of its reversibility.

PMID- 17024535
TI  - Improved abdominal wall wound healing by helium pneumoperitoneum.
AB  - BACKGROUND: Despite widespread use of the endoscopic technique in the treatment
      of inguinal and incisional hernias, knowledge about its impact on abdominal wall
      wound healing is rare. Questions remain regarding the risk of port-site hernias
      and hernia recurrence. The current study investigated the gas-dependent effects
      of pneumoperitoneum on laparotomy wound healing. METHODS: Laparotomy was
      performed in 54 male Sprague-Dawley rats. A carbon dioxide (n = 18) or helium (n
      = 18) pneumoperitoneum of 3 mmHg was maintained before and after laparotomy, with
      an overall duration of 30 min. The rats in the control group (n = 18) received no
      pneumoperitoneum. The animals were killed after 5 and 10 days, and the abdominal
      wall was explanted for subsequent histopathologic examinations of the laparotomy
      wound. The granuloma formation in hematoxylin and eosin-stained sections was
      analyzed. Infiltration of macrophages (CD68) and expression of matrix
      metalloproteinases (MMP-8 and MMP-13) were examined by immunohistochemistry. The
      collagen type 1 to type 3 ratio was investigated by cross-polarization microscopy
      after Sirius Red staining. RESULTS: After 5 and 10 days, the percentages of CD68
      positive cells, granuloma formation, and expression of MMP-8 did not differ
      between the groups. In contrast, after both 5 and 10 days, the expression of MMP
      13 and the collagen 1 to 3 ratio were significantly higher after helium
      pneumoperitoneum than in the control animals. CONCLUSION: The results suggest
      that helium pneumoperitoneum may ameliorate wound healing within the abdominal
      wall and could therefore represent a beneficial gas for endoscopic hernia repair.

PMID- 17024536
TI  - Impact of prior surgery on the feasibility of laparoscopic surgery for children:
      a prospective study.
AB  - BACKGROUND: This study aimed to determine the impact of prior surgery on the
      feasibility of laparoscopic surgery for children. METHODS: A prospective study
      analyzed 471 consecutive children who underwent laparoscopic surgery over a 4
      year period. Laparoscopic procedures were classified "easy," "difficult," or
      "demanding." The end points of the study were conversion rate, intraoperative
      events, and duration of operation. RESULTS: A total of 89 patients (19%) had
      undergone previous abdominal surgery. The conversion rate was 18% for the
      patients with prior surgery versus 9% for those without a prior operation (16/89
      vs 35/382; p < 0.05). This difference reflects a significantly higher conversion
      rate for "easy" procedures among patients with than among those without prior
      surgery, but not for "difficult" and "demanding" procedures. The type of prior
      surgery had no significant impact on the mean duration of the operation. Of 71
      procedures, 12 (17%) after prior conventional surgery were converted, as compared
      with 4 (22%) of 18 after prior laparoscopy (p > 0.05). Intraoperative events,
      mainly attributable to adhesions and lack of overview, occurred in 8% of patients
      with prior procedures, as compared with 2% without former surgery (7/89 vs 9/382;
      p < 0.05). Relevant complications were not significantly more frequent after
      prior surgery. The incidence of conversions decreased with increased time between
      current and previous surgery. It was 64% for surgeries less than 1 year later,
      25% for surgeries 1 to 5 years later, and 5% for surgeries more than 5 years
      later (7/11 vs 6/24 vs 3/54; p < 0.001). CONCLUSIONS: Prior surgery has a limited
      impact on the feasibility of laparoscopic surgery for children. The conversion
      rate and the incidence of intraoperative events, mainly because of adhesions and
      lack of overviewing, is increased, but not the incidence of relevant
      complications. The feasibility improves considerably with increased time between
      surgery and prior surgery. The authors consider laparoscopy to be the first
      choice technique after prior surgery.

PMID- 17024537
TI  - Influence of colorectal laparoscopic surgery on dissemination and seeding of
      tumor cells.
AB  - BACKGROUND: This study aimed to compare the influence of colorectal laparoscopic
      surgery and conventional surgery on dissemination and seeding of tumor cells.
      METHODS: Intraoperative peritoneal lavage cytology was performed for 36 patients
      with colorectal cancer during colorectal laparoscopic surgery and for 45 patients
      with colorectal cancer during conventional surgery. Cytology was examined twice:
      immediately after opening of the peritoneal cavity and just before closure of the
      abdomen. Saline was poured into the peritoneal cavity, and 100 ml fluid was
      retrieved after irrigation. Laparoscopic instruments were lavaged after surgery
      with 100 ml of saline. Carbon dioxide (CO(2)) was derived through the trocar side
      orifice after pneumoperitoneum during laparoscopic coloectomy and filtered
      through 100 ml of saline. Cytologic examination of the filtrate was performed
      after the filtration process, smear, cell block, and staining. RESULTS: Malignant
      cells were not detected in the CO(2) filtrate gas. The incidence of positive
      cytology in the lavage of the instruments during laparoscopic surgery was 2.78%.
      The incidence of positive cytology during laparoscopic surgery was 33.33% in the
      prelavage and 8.33% in the postlavage. The incidence of positive cytology during
      conventional surgery was 33.33% in the prelavage and 11.11% in the postlavage.
      CONCLUSION: During colorectal laparoscopic surgery, CO(2) pneumoperitoneum does
      not affect tumor cell dissemination and seeding. In this study, laparoscopic
      techniques used in colorectal cancer surgery were not associated with a greater
      risk for intraperitoneal dissemination of cancer cells than the conventional
      technique.

PMID- 17024538
TI  - Treatment of varicocele with reference to age: a retrospective comparison of
      three minimally invasive procedures.
AB  - BACKGROUND: This study investigated whether the therapeutic efficacy and
      morbidity of three minimally invasive techniques for varicocele correction-
      laparoscopic varicocelectomy (LV), antegrade sclerotherapy (AS), and retrograde
      embolization (RE)--differed between children and adults. METHODS: During a 10
      year period, 356 procedures for varicocele correction, including 122 cases of LV,
      108 cases of AS, and 126 cases of RE, were performed for 314 patients at our
      institution. Of these patients, 223 were 19 years of age or younger (group 1),
      and 133 were older than 19 years (group 2). Diagnosis and postoperative results
      were established clinically and with the use of Doppler ultrasonography. The
      failure rates and complications for each procedure were retrospectively evaluated
      and compared between the two age groups. RESULTS: The median follow-up period was
      69 months (range, 6-122 months). For 25 patients (19.8%), RE was not feasible for
      technical reasons. In both groups, LV had a lower failure rate than AS or RE, but
      the difference between LV and AS was not significant in group 1 (7.7(% vs 11.9%;
      p > 0.5). Also in group 1, AS was associated with fewer complications than LV 1
      (4.5% vs 15.4%; p < 0.05). In group 2, LV was significantly more effective in
      correcting varicoceles than the other two techniques (p < 0.01). In this group,
      the complication rates for all three procedures did not differ significantly (p >
      0.05). CONCLUSIONS: In our experience, LV was more effective than AS or RE in
      correcting varicoceles. For children and adolescents, AS may be more indicated
      because of the slightly lower complication rate and similar recurrence rates, as
      compared with LV, for this age group. The higher incidence of postoperative
      hydrocele formation after LV warrants more refined techniques such as the
      lymphatic-sparing approach.

PMID- 17024539
TI  - Use of alarm symptoms to select dyspeptics for endoscopy causes patients with
      curable esophagogastric cancer to be overlooked.
AB  - BACKGROUND: In August 2004, the United Kingdom Department of Health advisory body
      published dyspepsia referral guidelines for primary care practitioners. These
      guidelines advised empiric treatment with antisecretory medications and referral
      for endoscopy only in the presence of alarm symptoms. The current study aimed to
      evaluate the effect of these guidelines on the detection of esophagogastric
      cancer. METHODS: The study reviewed a prospectively compiled database of 4,018
      subjects who underwent open access gastroscopy during the years 1990 to 1998. The
      main outcome measures for the study were cancer detection rates, International
      Union Against Cancer (UICC) stage, and survival. RESULTS: Gastroscopy identified
      esophagogastric carcinoma in 123 (3%) of the 4,018 subjects. Of these 123
      patients, 104 (85%) with esophagogastric cancer had "alarm" symptoms (anemia,
      mass, dysphagia, weight loss, vomiting) and would have satisfied the referral
      criteria. The remaining 15% would not have been referred for initial endoscopic
      assessment because their symptoms were those of uncomplicated "benign" dyspepsia.
      The patients with "alarm" symptoms had a significantly more advanced tumor stage
      (metastatic disease in 47% vs 11%; p < 0.001), were less likely to undergo
      surgical resection (50% vs 95%; p < 0.001), and had a poorer survival (median, 11
      vs 39 months; p = 0.01) than their counterparts without such symptoms.
      CONCLUSIONS: The use of alarm symptoms to select dyspeptics for endoscopy
      identifies patients with advanced and usually incurable esophagogastric cancer.
      Patients with early curable cancers often have only dyspeptic symptoms, and their
      diagnosis will be delayed until the symptoms of advanced cancer develop.

PMID- 17024540
TI  - Elective laparoscopically assisted sigmoidectomy for the sigmoid volvulus.
AB  - BACKGROUND: The laparoscopic approach for the treatment of sigmoid volvulus has
      been a rare surgical indication. This phase 2 study investigated the feasibility
      and surgical outcomes of elective laparoscopic surgery for sigmoid volvulus.
      METHODS: Patients with sigmoid volvulus were first offered colonoscopic
      decompression for their acute colonic obstruction. If the colonic decompression
      was successful, complete bowel preparation was performed, followed by elective
      laparoscopically assisted sigmoidectomy. The details of the laparoscopic
      procedures are shown in the video. Briefly, the redundant sigmoid colon is
      totally mobilized by a laparoscopic medial-to-lateral dissection sequence, after
      which it is exteriorized, transected, and reconstructed by end-to-end
      anastomosis. In the authors' experience, the medial-to-lateral approach is highly
      efficient for the laparoscopic mobilization of the redundant sigmoid colon. We
      believe that the longer the lateral abdominal wall attachment of the sigmoid
      colon is preserved, the better the exposure and the easier the dissection. If the
      risk of anastomotic leakage is considered high in a specific case, protective
      ileostomy is selectively preformed. Before entering the current study, the
      patients were well informed about the advantages and disadvantages of
      laparoscopic surgery. The enrollment of patients was selective according to the
      appropriate eligibility criteria. This study was approved by the Institutional
      Review Board of the National Taiwan University Hospital. The patients'
      clinicopathologic data and surgical outcomes were prospectively evaluated.
      RESULTS: Between August 2001 and April, 2005, a total of 14 patients (10 men and
      4 women) with sigmoid volvulus were treated with the described procedure. The age
      distribution of the patients was 68.4 +/- 12.2 years. The attack of sigmoid
      volvulus was the first episode for eight patients, the second episode for 4
      patients, and the third episode (or more) for two patients. The body mass index
      (BMI) of the patients was 26.8 +/- 4.4 kg/m(2). The physical status
      (classification of American Society of Anesthesiology [ASA]) was 1 for five
      patients, 2 for eight patients, and 3 for 1 patient. During the laparoscopy, all
      the patients presented with the pathognomonic findings of sigmoid volvulus
      including redundant sigmoid colon, narrow sigmoid mesenteric pedicle, and
      mesosigmoiditis with mesenteric fibrosis and scarring, as shown in the video. The
      length of the resected colon was 32 +/- 6 cm. The operation time was 194.6 +/-
      32.4 min, and the blood loss was 44.0 +/- 12.4 ml. The abdominal wound consisted
      of four 5 to 12 mm working ports and a 5 cm major wound for exteriorization of
      the sigmoid colon. Some surgeons have shown that a sigmoid volvulus can be
      resected through a 5-cm left lower quadrant incision with very little
      mobilization of the colon because of its redundancy. In this context, the
      laparoscopic approach competed with the minilaparotomy method in terms of
      adequate sigmoid resection, lysis of mesosigmoid adhesion, and tension-free
      colorectal anastomosis. Protective ileostomy was performed for the only patient
      with a physical status of ASA 3. There was no mortality in this case series.
      However, pneumonia developed postoperatively in one patient, acute myocardial
      infarction in one patient, and wound infection in two patients. Excluding the two
      patients who experienced postoperative pneumonia and acute myocardial infarction,
      the duration of the postoperative ileus was 48 +/- 12 h, the postoperative
      hospitalization was 7 +/- 1 days, and the degree of postoperative pain was 3.5 +/
      0.5 according to the visual analog scale. The return to partial activity
      required 18 +/- 2.5 days, and the return to full activity required 28.4 +/- 5.6
      days. As compared with the overall costs for a conventional sigmoid colectomy,
      which are completely covered by the National Bureau of Health Insurance of
      Taiwan, the expenses for the patients undergoing laparoscopic procedures were
      significantly higher by approximately 24,000.0 NT dollars +/- 2,635.0 (1 U.S.
      dollar = 32 NT dollars). These higher expenses must be borne by the patients
      themselves. CONCLUSION: Considering that patients with sigmoid volvulus often are
      elderly and chronically ill, laparoscopic elective surgery after a successful
      colonoscopic decompression may be a good choice for a selected group of patients
      in terms of minimized surgical complications and quick convalescence.

PMID- 17024541
TI  - Laparoscopic fundoplication: a 10-year learning curve.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has become the most common
      surgical treatment for gastroesophageal reflux disease (GERD). Controversies
      still exist regarding the operative technique and the durability of the
      procedure. METHODS: A retrospective study of 808 patients undergoing 838 LNF for
      GERD at a tertiary referral center was undertaken. Demographic, perioperative,
      and follow-up data had been entered onto the unit database. RESULTS: During a
      median follow-up period of 60 months (range, 2-120 months), heartburn decreased
      to 3% of the patients (19/645) and regurgitation to 2% (11/582) (p < 0.01).
      Respiratory symptoms improved in 69 (85%) of 81 patients (p < 0.01). The
      incidence of postoperative dysphagia was unaffected by the use of an
      intraesophageal bougie (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.82
      1.64; p = 0.41) or division of the short gastric vessels (OR, 0.84; 95% CI, 0.42
      1.07; p = 0.72). In the immediate postoperative period, the incidence of
      abdominal symptoms increased by 10% (p < 0.01) and dysphagia by 16% (p < 0.01).
      After 10 postoperative years, only 3% (30/484) were found to have abdominal
      symptoms, whereas the incidence of dysphagia declined to zero. CONCLUSION: The
      findings show that LNF is a safe and effective procedure with long-term
      durability. Abdominal symptoms and dysphagia are the principal postoperative
      complaints, which improve with time. Personal preference should dictate the use
      of a bougie, division of the short gastric vessels, or both.

PMID- 17024542
TI  - Effect of a pneumoperitoneum on systemic cytokine levels, bacterial
      translocation, and organ complications in a rat model of severe acute
      pancreatitis with infected necrosis.
AB  - BACKGROUND: Infection of pancreatic necrosis (IPN) is strongly associated with
      sepsis and multiple organ dysfunction and is an absolute indication for surgery.
      Patients with IPN are critically ill at the time of surgery and may benefit from
      a minimally invasive approach with reduced surgical trauma. Recently, several
      minimally invasive necrosectomy techniques have been reported. However, the
      effects and potential dangers of a pneumoperitoneum in IPN cases are unknown.
      This study aimed to determine the effects of a pneumoperitoneum on systemic
      cytokine levels, bacterial translocation, and systemic organ complications in a
      rat model of IPN. METHODS: For this study, IPN was induced in Wistar rats using
      retrograde intraductal infusion of 3% taurocholate. After 8 h, the animals were
      subjected to either laparoscopy (pneumoperitoneum at 8 mmHg) or laparotomy for 1
      h and killed after 1 or 3 h. Severe acute pancreatitis with IPN was proved by
      serum amylase and lipase, histology, tissue activity of myeloperoxidase (MPO),
      and bacteriology. Systemic levels for interleukin-10 (IL-10), IL-6, tumor
      necrosis factor-alpha (TNF-alpha), and lipopolysaccarides were determined by
      enzyme-linked immunoassay (ELISA). Systemic organ damage and dysfunction were
      evaluated using MPO activity (lung), serum creatinine (kidney), and serum
      aminotransferases (liver). RESULTS: Necrotizing pancreatitis developed in all the
      animals. Most of the animals (85%) had proven infected necrosis. Elevated
      cytokine levels and deteriorated organ parameters demonstrated systemic
      inflammation and organ failure. Although there was a tendency toward a higher
      level of proinflammatory cytokines after laparotomy, there were no significant
      differences between laparotomy and laparoscopy. Furthermore, these alterations
      were not accompanied by any differences in bacterial translocation
      (lipopolysaccharides), systemic organ damage, or mortality between laparoscopy
      and laparotomy. CONCLUSION: In the current model of infected pancreatic necrosis,
      a pneumoperitoneum did not result in increased cytokine release or bacterial
      translocation. However, the putative advantage of less surgical trauma with the
      laparoscopic approach did not play a significant role in the setting of severe
      acute pancreatitis with IPN.

PMID- 17024543
TI  - Thoracoscopic robot-assisted bronchoplasty.
AB  - BACKGROUND: In robotic surgery, the ideal position of the system, as well as the
      optimal working angles and the proper positioning of the thoraco ports position
      is very important. No robot-assisted bronchoplasty has been reported. Our study
      describes use of the da VinciTM surgical system (Intuitive Surgical, Inc.) for
      robotic sleeve upper lobectomy in a human fresh cadaver. METHODS: A male cadaver
      was placed in the left lateral decubitus position. After thoracoscopic upper
      lobectomy was performed through the working port and the two ports, the robotic
      system was then set up behind the cadaver. The working port allowed introduction
      of the optical scope and the robotic surgical arms were inserted into the thoraco
      ports. The right bronchus was dissected and wedge was cut out with the robotic
      scissors. After standard lymph node dissection, end-to-end bronchial anastomosis
      was performed with robotic instruments. Once the anastomosis was complete, air
      leakage was checked with saline solution placed in the pleural cavity. RESULTS:
      Thoracoscopic robot-assisted bronchoplasty was performed successfully.
      CONCLUSIONS: In evaluating various positions of the system we demonstrated that
      our technique is sufficient approaches to robotic bronchoplasty. This procedure
      offers specific advantages over conventional bronchoplasty with accuracy and
      safety.

PMID- 17024544
TI  - A prototype ultrasound-guided laparoscopic radiofrequency ablation system.
AB  - BACKGROUND: Advanced laparoscopic procedures, particularly laparoscopic liver
      resection and ablation, may benefit from image-guided surgery techniques that
      involve interactive three-dimensional imaging and instrument tracking. METHODS: A
      prototype system for laparoscopic ultrasound-guided radiofrequency ablation was
      designed and implemented. This system uses an infrared camera to track
      instruments and runs on a personal computer. Features of the system include
      spatially registered ultrasound visualization, volume reconstruction, and
      interactive targeting. Targeting of accuracy studies was performed by directing a
      tracked needle to a phantom target. RESULTS: Ultrasound data collection and
      volume reconstruction can be achieved within minutes and interactively reviewed
      by the surgeon. Early results with phantom experiments demonstrate a targeting
      accuracy of 5 to 10 mm. CONCLUSIONS: These results support the further
      development of this and similar image-guided surgery systems for specific
      laparoscopic procedures. Eventually, rigorous clinical evaluation will be
      necessary to prove their value.

PMID- 17024545
TI  - Eosinophilic esophagitis in infants and toddlers.
AB  - Feeding refusal is often described in conjunction with the diagnosis of
      eosinophilic esophagitis (EE) in pediatric patients; however, there are little
      data regarding the specific clinical manifestations and effective management of
      this condition in very young children. The aim of this study was to evaluate the
      presentation of EE in infants and toddlers referred to the Interdisciplinary
      Feeding Team Clinic of a tertiary referral center and to document responses to
      treatment. Database matching was performed (from January 2000 to June 2003) to
      identify infants and toddlers diagnosed with EE who had been referred to the
      Interdisciplinary Feeding Team Clinic. Endoscopic features required for a
      diagnosis of EE included esophageal mucosal furrowing, erythema, exudates, or
      decreased vascular markings. Histologic features of EE were more than 24
      eosinophils per high-power field (HPF), thickening of basal cell layer, and
      papillary (rete peg) lengthening or elongation. All study patients were treated
      with a combination of proton pump inhibitors (PPI) and fluticasone (swallowed).
      In addition, elemental diet was instituted in those documented to have a food
      allergy. Treatment success was defined by an improved oral intake, adequate
      weight gain, and improved endoscopic and histologic findings at 3-6-month
      followup. A total of 15 subjects [mean age = 19.9 months (SD = 9.7 months)] who
      fulfilled the entry criteria during the study period were identified. All 15
      children had documented endoscopic improvement and 14/15 children had histologic
      resolution of EE after therapy. In 13 of the 15 children, this translated to
      clinical improvement as well.

PMID- 17024546
TI  - The influence of orolingual pressure on the timing of pharyngeal pressure events.
AB  - This study explored the influence of two methods of effortful swallow execution
      on the timing of pharyngeal pressure events. Participants were asked to either
      emphasize or minimize tongue-to-palate contact during performance of the
      maneuver. Twenty healthy participants were evaluated using concurrent submental
      surface electromyography (sEMG), orolingual manometry, and pharyngeal manometry.
      Each subject performed three repetitions of three counterbalanced tasks
      (noneffortful dry swallows, effortful dry swallows with tongue-to-palate
      emphasis, and effortful dry swallows with tongue-to-palate de-emphasis). Four
      variables were measured: Onset Lag vs. sEMG Peak, Peak Lag vs. sEMG Peak, Total
      Duration, and Percent Rise Time to Peak. Compared to noneffortful swallows, the
      effortful swallow task elicited significantly earlier onsets and peaks of
      pharyngeal pressures relative to the submental sEMG peak. Total pressure event
      durations were greater and rise times were significantly shorter. When comparing
      the two methods of effortful swallow execution, a longer latency to peak proximal
      pharyngeal pressure was found in the tongue-to-palate emphasis condition. These
      results support the interpretation that the effortful swallow maneuver involves
      generation of higher velocity bolus driving forces that propel the bolus into and
      through the pharynx with greater efficiency and that pressure is then sustained
      to facilitate more complete bolus clearance.

PMID- 17024547
TI  - Dysphagic patients with tracheotomies: a multidisciplinary approach to treatment
      and decannulation management.
AB  - In 2000 a multidisciplinary protocol for weaning dysphagic patients from the
      tracheotomy tube and a decannulation decision chart created according to
      principles of the F.O.T.T.((R)) Concept (Face and Oral Tract Therapy) were
      introduced in the Swiss Neurological Rehabilitation Centre REHAB in Basel. In the
      present study we introduce these guidelines and present an evaluation of the
      treatment and decannulation procedure. We retrospectively compared data from
      patients before and after introduction of the multidisciplinary procedure with
      regard to mean cannulation times and success of decannulation. Furthermore, we
      analyzed the rehabilitation progress of the group who underwent multidisciplinary
      treatment as well as the participation of the speech language therapist. The
      results show that the treatment introduced to improve swallowing functions and
      wean patients from the tracheotomy tube led to a fast and safe decannulation of
      our patients. The mean length of cannulation time was reduced significantly.
      After decannulation the patients showed clear functional improvements.
      Interdisciplinary treatment using the approach discussed in this study can be
      considered efficient and an important basis for further functional progress in
      the rehabilitation process.

PMID- 17024548
TI  - Utility of ambulatory pH monitoring and videofluoroscopy for the evaluation of
      patients with globus pharyngeus.
AB  - Globus pharyngeous is not an uncommon disorder. The precise pathophysiology
      remains unclear. The aim of this study was to assess the clinical value of
      videofluoroscopy and ambulatory pH monitoring in patients with globus pharyngeus.
      Twenty-three patients (11M/12F, age range = 21-74 yr, mean = 50 yr) with globus
      pharyngeus entered the study. Radiographic examination of the pharynx and
      esophagus included videofluoroscopy and static radiography. A dual probe to
      measure the proximal and distal intraesophageal pH was inserted for 24 h. The
      results of dual-probe pH monitoring were normal in all patients.
      Videofluoroscopic results were abnormal in 8 patients, with 5 patients having
      laryngeal aspiration, 2 having stasis of barium in the vallecula and pyriform
      sinuses, and 4 having poor pharyngeal elevation. Cervical osteophytes were found
      in 13 patients with a frequent location at the C5-6 level. Ambulatory pH
      monitoring seemed to be less helpful for the evaluation of globus pharyngeus
      without reflux-like symptoms. Pharyngeal dysfunction is detected in a substantial
      proportion of patients by videofluoroscopy and radiography.

PMID- 17024549
TI  - Neuroleptic-induced dysphagia: case report and literature review.
AB  - Neuroleptic medication may cause extrapyramidal symptoms (EPS) that can affect
      swallowing as well. This report describes a case of drug-induced dysphagia in a
      53-year-old man receiving haloperidol for treatment of schizophrenia. The
      diagnosis was established by fiberoptic endoscopic evaluation of swallowing.
      After changing medication to fluphenazin, dysphagic symptoms resolved. The
      literature on EPS-related dysphagia, its demographic features, typical symptoms,
      diagnostic modalities, clinical course, and treatment options is reviewed.

PMID- 17024550
TI  - Radiation dose in videofluoroscopic swallow studies.
AB  - Videofluoroscopy has become an increasingly important armament in the
      investigation and assessment of swallowing disorders. However, very little work
      has been published on the radiation dose used in such examinations and currently
      there is no national diagnostic reference level in the United Kingdom.
      Videofluoroscopy in our hospital is performed predominantly by one radiologist
      (IZM) in a single fluoroscopy room. We recorded the screening times of 230
      patients over a 45-month period. Screening time ranged from 18 to 564 s (median =
      171 s) associated with a median dose-area product of 1.4 Gy cm(2). This is below
      the third quartile level of 2.7 Gy cm(2) for all such examinations performed
      across the northern England. The effective dose associated with a typical
      videofluoroscopy dose-area product is 0.2 mSv. Videofluoroscopy is the most
      appropriate instrumental examination for assessing oropharyngeal swallow
      biomechanics and intervention strategies. This data set is based on the largest
      number of videofluoroscopy swallow studies published to date. Our results show
      that videofluoroscopy can be performed using minimal radiation doses.

PMID- 17024551
TI  - Application of the convection-dispersion equation to modelling oral drug
      absorption.
AB  - Models of systemic drug absorption after oral administration are frequently based
      on a direct or a delayed first-order rate process. In practice, the use of the
      first-order approach to predict drug concentrations in blood plasma frequently
      yields a considerable mismatch between predicted and measured concentration
      profiles. This is particularly true for the upswing of the plasma concentration
      after oral administration. The current investigation explores an alternative
      model to describe the absorption rate based on the convection-dispersion equation
      describing the transport of chemicals through the GI tract. This equation is
      governed by two parameters, transport velocity and dispersion coefficient. One
      solution of this equation for a specific set of initial and boundary conditions
      was used to model absorption of paracetamol in a 22-year-old man after oral
      administration. The GI-tract passage rate in this subject was influenced by co
      administration of drugs that stimulate or delay gastric emptying. The transport
      limited absorption function is more accurate in describing the plasma
      concentration versus time curve after oral administration than the first-order
      model. Additionally, it provides a mechanistic explanation for the observed curve
      through the differences in GI-tract passage rate.

PMID- 17024552
TI  - A delayed nonlinear PBPK model for genistein dosimetry in rats.
AB  - Genistein is an endocrine-active compound (EAC) found in soy products. It has
      been linked to beneficial effects such as mammary tumor growth suppression and
      adverse endocrine-related effects such as reduced birth weight in rats and
      humans. In its conjugated form, genistein is excreted in the bile, which is a
      significant factor in its pharmacokinetics. Experimental data suggest that
      genistein induces a concentration-dependent suppression of biliary excretion. In
      this article, we describe a physiologically based pharmacokinetic (PBPK) model
      that focuses on biliary excretion with the goal of accurately simulating the
      observed suppression. The mathematical model is a system of nonlinear
      differential equations with state-dependent delay to describe biliary excretion.
      The model was analyzed to examine local existence and uniqueness of a solution to
      the equations. Furthermore, unknown parameters were estimated, and the
      mathematical model was compared against published experimental data.

PMID- 17024554
TI  - Poor prognosis for biomarkers.

PMID- 17024553
TI  - FDG-PET detected thyroid incidentalomas: need for further investigation?
AB  - BACKGROUND: Incidental thyroid abnormalities are increasingly detected in
      patients undergoing PET scans. The aim of this study was to review our experience
      with the management of PET detected thyroid incidentalomas in a large single
      institution series. METHODS: All PET scans performed from May 2003 to July 2005
      were reviewed and patients with incidental thyroid abnormalities were identified.
      From this group, patients that underwent further investigation were analyzed.
      Data relating to PET scan findings, FNA diagnoses, operative details, and
      histopathology was reviewed. RESULTS: In 8,800 patients, 16,300 PET scans were
      performed of whom 263 patients (2.9% of patients and 1.6% of PET scans) had
      findings positive for thyroid abnormality. Thyroid malignancy was noted in 42%
      (24 patients) of the 57 patients that underwent FNA. In the group of 27 patients
      that were subjected to operative intervention, 74% (20 patients) were noted to
      have a malignant diagnosis. The final histopathology revealed primary thyroid
      carcinoma in all these 20 patients (19 patients with papillary carcinoma and one
      patient with primary thyroid lymphoma). The factors that correlated with an
      increased risk of malignancy were the presence of physical finding (p = 0.01) and
      focal (p < 0.01) or unilateral uptake (p < 0.01) on PET scan. The average SUV was
      not useful in differentiating benign (9.2) from malignant lesions (8.2, p = 0.7).
      CONCLUSIONS: PET detected incidental thyroid abnormalities are rare. In patients
      with positive PET scan findings and suspicious features, the incidence of primary
      thyroid malignancy is very high. These patients warrant further investigation
      followed by possible operative intervention.

PMID- 17024555
TI  - Prognostic groups in colorectal carcinoma patients based on tumor cell
      proliferation and classification and regression tree (CART) survival analysis.
AB  - BACKGROUND: In this study, an alternative analytical method was used to model
      colorectal cancer (CRC) patients' long-term survival by assessing the prognostic
      value of the Ki-67 protein as a marker of tumor cell proliferation, and to
      illustrate the interaction between standard clinicopathologic variables and the
      proliferation marker in relation to their impact on survival. METHODS: A cohort
      of 106 surgically treated CRC patients was used for analysis. The expression of
      the cell-cycle-related Ki-67 protein in tumor samples was evaluated by
      immunohistochemistry. A score was assigned as the percentage of positive tumor
      cell staining, denoted as proliferation index (PI), and was used in a
      multivariate analysis using a recursive partitioning algorithm referred to as
      classification and regression tree (CART) to characterize the long-term survival
      after surgery. RESULTS: Of the covariates selected for their prognostic value, PI
      contributed most to the classification of survival status of patients. However,
      CART analysis selected the presence of distant metastasis as the best first split
      up factor for predicting 5-year survival. CART then selected the following
      covariates for building up subgroups at risk for death: (1) PI; (2) pathological
      lymph node metastasis; (3) tumor size. Seven terminal subgroups were formed, with
      an overall misclassification rate of 16%. CONCLUSIONS: These analyses
      demonstrated that a Ki-67-protein-based tumor proliferation index appeared as an
      independent prognostic variable that was consistently applied by the CART
      algorithm to classify patients into groups with similar clinical features and
      survival.

PMID- 17024556
TI  - Sentinel lymph node biopsy for atypical melanocytic lesions with spitzoid
      features.
AB  - INTRODUCTION: Sentinel lymph node biopsy (SLNB) is routinely used as a staging
      procedure for melanomas, however may also assist in understanding the biology of
      atypical and controversial spitzoid melanocytic skin lesions. METHODS: Five
      hundred and forty-nine sentinal lymph node excisions were performed over a 5-year
      period. Fourteen patients with controversial melanocytic lesions were identified
      and of these ten underwent SLNB. The histology of the primary skin lesion and
      corresponding sentinal lymph nodes were evaluated and correlated with outcome.
      RESULTS: Thickness of the primary melanocytic lesion ranged from 1.22 to 4 mm.
      Fifty percent of patients were less than 17 years of age. Ten patients underwent
      SLNB and three cases (30%) displayed metastatic disease in the SLNB specimen. All
      three patients were under 17 years of age and all underwent completion axillary
      dissection. One completion axillary dissection had an additional node with
      metastasis on routine H&E and immunohistochemical staining. No capsular invasion
      was seen. All three cases with metastatic disease received adjuvant systemic
      therapy and remain disease free at 29, 49 and 57 months follow-up. All patients
      with a negative SLNB remain disease free at mean follow-up of 28.1 months (range:
      13-40 months). CONCLUSION: Our results confirm that some of these spitzoid
      lesions metastasize to regional lymph nodes and SLNB is a valuable adjunct tool
      in staging these lesions. However, molecular studies and a prolonged follow-up
      are needed to determine whether these lesions, especially those occurring in
      children are comparable to stage matched overt melanoma in adults.

PMID- 17024557
TI  - Disruption of the middle hepatic vein is not crucial for liver regeneration of
      the remnant liver after right hemihepatectomy for hepatic tumors.
AB  - BACKGROUND: To clarify the role of the middle hepatic vein (MHV) in liver
      regeneration of the remnant liver after right hemihepatectomy for hepatic tumors,
      we reviewed 29 patients to evaluate liver regeneration for up to 12 postoperative
      months. METHODS: Volume regeneration of the remnant liver was investigated by
      computed tomography at 3, 6, and 12 postoperative months. The remnant liver was
      divided into the following three areas: the medial section (segment IV), the
      lateral section (segments II and III), and segment I. The patients were divided
      into two groups: group A (n = 17), in which the MHV was preserved in the remnant
      liver, and group B (n = 12), in which the MHV was removed. RESULTS: Volume
      regeneration of each area continued until 6 postoperative months but did not
      increase thereafter. On univariate analysis, differences in the volume
      regeneration of each area between the groups were not significant at any measured
      time point. Furthermore, disruption of the MHV was determined to not be crucial
      to the volume regeneration of any liver area on multivariate analysis. Only the
      resection volume (percentage) significantly affected liver regeneration of the
      remnant liver. CONCLUSIONS: Disruption of the MHV does not decisively affect
      liver regeneration of remnant liver after right hemihepatectomy for hepatic
      tumors.

PMID- 17024558
TI  - Complications after extended (D2) and superextended (D3) lymphadenectomy for
      gastric cancer: analysis of potential risk factors.
AB  - BACKGROUND: Very few studies from Western centers have compared D2 and D3
      dissection in the surgical treatment of gastric cancer. The aim of the
      prospective observational study reported here was to analyze the postoperative
      outcome and potential risk factors for complications following D2 and D3
      lymphadenectomy. METHODS: A total of 330 consecutive patients, of which 251
      submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were
      enrolled in the study. Twenty potential risk factors for morbidity and mortality
      were studied by means of univariate and multivariate analysis. RESULTS: Overall
      morbidity and mortality rates were 34% (111 patients) and 4% (14 patients),
      respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases
      and pancreatitis were the most commonly observed complications. No differences in
      morbidity, surgical morbidity, mortality rates and mean hospital stay between D2
      and D3 lymphadenectomy were found. Multivariate analysis revealed that American
      Society of Anesthesiologists' (ASA) class II/III versus class I, perioperative
      blood transfusions, and low albumin serum levels were independent predictors of
      postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low
      albumin serum levels independently predicted mortality. Mortality rate was .5% in
      the 203 patients aged 75 years or younger who underwent curative surgery. Most of
      deaths were observed in patients older than 75 years with low albumin serum
      levels or treated by non-curative surgery. CONCLUSIONS: D2 lymphadenectomy
      represents a feasible procedure associated to acceptable morbidity and mortality
      rates. In specialized centers, D3 lymphadenectomy may be performed without
      increasing the risk of postoperative complications and associated deaths in
      carefully selected patients. These techniques should be avoided in subgroups of
      patients with a high risk of postoperative mortality.

PMID- 17024559
TI  - Thyroid hormone changes cardiomyocyte shape and geometry via ERK signaling
      pathway: potential therapeutic implications in reversing cardiac remodeling?
AB  - It has previously been shown that thyroid hormone can reverse cardiac remodeling
      in failing hearts by reducing myocardial wall stress due to the unique changes
      induced in cardiac myocyte shape. This effect may be of therapeutic relevance.
      Therefore, the present study has investigated potential signaling mechanisms
      underlying the thyroid hormone action on cardiac myocyte shape and geometry.
      Neonatal cardiomyocytes were treated with T(3) while untreated cells served as
      controls. T(3) administration for 48 h significantly increased the ratio of the
      major to minor cell axis and changed their shape from an almost circular to an
      elongated form. Cell area and protein synthesis were increased and T(3) treated
      cells expressed 51% alpha-MHC and 49% beta-MHC as compared to 100% beta-MHC
      expression in non-treated cells. This response was accompanied by a 1.9-fold
      increase in phospho-ERK levels early at 8 min which, within 60 min, returned to
      the levels of the untreated cells. Phospho-JNK levels were significantly reduced
      within 60 min after T(3) treatment while no changes in the expression of phospho
      Akt and phospho-p38 MAPK were found between the T(3) treated and untreated cells.
      Administration of PD98059 (an inhibitor of ERK signaling) prevented the thyroid
      hormone induced changes in cardiomyocyte geometry and shape without a significant
      reduction in cell area and protein synthesis. In conclusion, T(3) induced changes
      in cardiomyocyte shape and geometry involve the ERK kinase signaling. This
      response is independent of the effects of T(3) on cell size and protein
      synthesis.

PMID- 17024560
TI  - Acetylcholinesterase inhibition and gill lesions in Rasbora caverii, an
      indigenous fish inhabiting rice field associated waterbodies in Sri Lanka.
AB  - The present study was aimed at applying condition factor (CF), brain
      acetylcholinesterase (AChE) and gill histology as biomarkers for detecting
      possible exposure/effect induced by pesticides in fish residing rice field
      associated waterbodies in Sri Lanka. Biomarkers of an indigenous fish, Rasbora
      caverii collected from five sampling sites including canals near rice fields, a
      river and a reservoir (the reference site) were evaluated at four sampling stages
      covering pesticide application periods during rice cultivation season in 2004.
      Results indicated that CF of the fish did not show significant alterations
      regardless of the sampling sites or sampling stages. Site specific differences in
      AChE activities of the fish were not evident either prior to application of
      pesticides or at 7 days after Paraquat application to the rice fields. Two days
      after the application of a mixture of Fenthion and Phenthoate to the rice fields,
      AChE activity of the fish collected from canals near rice fields was
      significantly depressed (65-75%) compared to the fish in the reference site. The
      activities remain depressed to 50-56% even at 65 days after the insecticides
      application. Laboratory studies showed that prior exposure of R. caverii to
      Paraquat (2 microg l(-1), 7 days) enhanced the extent of inhibition of brain AChE
      activity induced by Fenthion (3 microg l(-1)) or a mixture of Fenthion (3 microg
      l(-1)) and Phenthoate (5 microg l(-1)). Gills of fish collected from canals near
      rice fields exhibited abnormal multiple divisions at the tips of some secondary
      lamellae in addition to hyperplasia, hypertrophy and club shaped deformities.
      Results indicate that application of pesticides in rice culture could manifest a
      threat to native fish populations residing rice field associated waterbodies. The
      response of brain AChE and histological changes in the gills of R. caverii
      allowed differentiating sampling sites after insecticide applications to the rice
      fields. Hence, R. caverii may be considered as a surrogate species in
      ecotoxicological risk evaluation of agrochemicals in the region.

PMID- 17024561
TI  - Modeling responses of Daphnia magna to pesticide pulse exposure under varying
      food conditions: intrinsic versus apparent sensitivity.
AB  - Recent studies showed that limiting food conditions resulted in either increased
      or decreased sensitivity of Daphnia magna to toxicants. It remained unclear
      whether these contrasting food-dependent alterations in toxicity resulted from
      differences in intrinsic sensitivity of the daphnids or from changes in
      toxicokinetics and resource allocation. It is hypothesized here that, if food
      level only affects accumulation kinetics and resource allocation, then the
      intrinsic sensitivity to this toxicant should be the same for all food regimes.
      This hypothesis was investigated using the DEBtox model, which is based on the
      theory of Dynamic Energy Budgets. We examined results of two recently conducted
      life-cycle studies on the combined effects of food level and a pulsed exposure to
      the pyrethroid insecticide fenvalerate (FV) on D. magna. The model described the
      effects of the time-varying exposure well, and indicated that when the animals
      did not die from exposure to FV, full reversibility of toxic effects was
      possible, allowing a complete recovery. Results revealed furthermore that the
      data from both studies could be described by the same NECs for survival and
      assimilation, killing rate and tolerance concentration (132 (49.2-228) x 10(-6)
      microg/L, 0 (0-1.18 x 10(-5)) microg/L, 74.4 (55.6-96.4) L (microg d)(-1) and
      5.39 (2.72-18.5) x 10(-3) microg/L, respectively). It is therefore concluded that
      food-dependent FV toxicity can be explained by altered toxicokinetics and
      resource allocation, but not by changes in the intrinsic sensitivity of the
      daphnids. This study implies that the effect of pesticide application in the
      field depends on the trophic state of the receiving water body, but also that
      full recovery of survivors is possible after FV application.

PMID- 17024563
TI  - Programmed death-1 gene polymorphisms in patients with systemic lupus
      erythematosus in Taiwan.
AB  - To investigate the role of programmed cell death-1 (PD-1) gene polymorphisms in
      the development of systemic lupus erythematosus (SLE) in Taiwan, 109 patients
      with SLE and 100 healthy controls were enrolled in this study. The PD-1 gene
      polymorphisms were determined by the method of polymerase chain
      reaction/restriction fragment length polymorphism. This study showed that the
      genotype distributions of PD-1 7209 C/T polymorphisms were significantly
      different between the patients with SLE and controls (P=0.002, Pc=0.018). The
      frequencies of the PD-1 7209 C/C genotype and PD-1 7209 C allele were
      significantly higher in the patients with SLE than those of the controls
      (P=0.001, OR=2.6, 95% CI=1.5-4.6, and P=0.002, OR=2.1, 95% CI=1.3-3.4, Pc=0.018,
      respectively). Moreover, the association of PD-1 7209 C with susceptibility to
      SLE was independent of the PD-1 ligand. This study also showed that the PD-1-536
      A 7146 G 7209 C 7499 G haplotype was associated with the development of SLE in
      Taiwan.

PMID- 17024562
TI  - Structural basis of chemokine receptor function--a model for binding affinity and
      ligand selectivity.
AB  - Chemokine receptors play fundamental roles in human physiology from embryogenesis
      to inflammatory response. The receptors belong to the G-protein coupled receptor
      class, and are activated by chemokine ligands with a range of specificities and
      affinities that result in a complicated network of interactions. The molecular
      basis for function is largely a black box, and can be directly attributed to the
      lack of structural information on the receptors. Studies to date indicate that
      function can be best described by a two-site model, that involves interactions
      between the receptor N-domain and ligand N-terminal loop residues (site-I), and
      between receptor extracellular loop and the ligand N-terminal residues (site-II).
      In this review, we describe how the two-site model could modulate binding
      affinity and ligand selectivity, and also highlight some of the unique chemokine
      receptor features, and their role in function.

PMID- 17024564
TI  - Frequency and clinical manifestations of patients with primary immunodeficiency
      disorders in Iran: update from the Iranian Primary Immunodeficiency Registry.
AB  - Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases,
      characterized by an increased susceptibility to infections. A total of 930
      patients (573 males and 357 females) are registered in Iranian PID Registry
      (IPIDR) during three decades. Predominantly antibody deficiencies were the most
      common (38.4%), followed by congenital defects of phagocyte number and/or
      function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined
      T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and
      diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the
      most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia
      telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined
      immunodeficiency. The frequency of other PID disorders was less than 50 in number
      (<5%). There is an increasing trend in recognition of more PID in the recent
      years. Construction of such registry is not only important for its
      epidemiological aspect but also for its role in increasing the physician's
      knowledge about such disorders.

PMID- 17024565
TI  - Upregulation of mitochondrial gene expression in PBMC from convalescent SARS
      patients.
AB  - The observations that Lymphopenia is common in severe acute respiratory syndrome
      (SARS) patients and that peripheral blood mononuclear cell (PBMC) could be
      infected by SARS-CoV indicate that PBMC could be useful in identifying the gene
      expression profile in convalescent patients and tracing the host response to SARS
      CoV infection. In this study, the altered genes expressions in the PBMC of
      convalescent SARS patients were investigated with suppression subtractive
      hybridization (SSH). We found that genes encoded by mitochondrial DNA (mtDNA)
      were obviously upregulated, while mitochondria were now found to be closely
      connected with antiviral immunity. The identification of a viral gene, M, in SSH
      cDNA library shows the long-term existence of SARS-CoV in vivo. In addition, some
      oxidative stress sensitive genes, heat shock proteins, transcription factors, and
      cytokines showed remarkable elevation. Thin-section electron microscope shows
      increased lysosome-like granule and mitochondria in PBMC of patients. These
      results provide important intracellular clue for tracing host response to SARS
      CoV infection and suggest a role of mitochondria in that process.

PMID- 17024566
TI  - Protein scission by metal ion-ascorbate system.
AB  - About 14 proteins were tested for specific oxidative scission catalyzed by metal
      ions in the presence of ascorbate and oxidizing agents (O(2) or hydrogen
      peroxide). Only four of them were degraded by Fe(3+)/Fe(2+)- ascorbate, twelve -
      by Cu(2+)/Cu(+)-ascorbate and two proteins (alpha- and beta-caseins) were
      degraded by Pd(2+) ions. The rate and the intensity of degradation are very
      different for various proteins. For the most of tested proteins only a small
      fraction of molecules was degraded. None of them was degraded completely. Two
      possible reasons of protein stability against oxidative degradation may be
      proposed as follows: either there is no metal binding site in a protein molecule,
      or metal binding ligands of protein undergo a rapid oxidative modification and
      the metal ion is released from the binding site. Human growth hormone was cut
      specifically at two sites by Cu(2+)/Cu(+)-ascorbate system. At least one of amino
      acid residues of this protein was modified by formation of reactive carbonyl.

PMID- 17024567
TI  - Down-regulation of phospholipase D2 mRNA in neonatal rat brainstem and cerebellum
      after hypoxia-ischemia.
AB  - Phospholipase D (PLD) and phosphatidylcholine (PC) were implicated in apoptosis
      and cancer. However, direct evidence on the role of PLD in the cause of apoptosis
      remains obscure. It was recently reported that apoptosis and necrosis could be
      induced in the cerebellum and brainstem after focal cerebral hypoxic-ischemic
      (HI) injury. It was found that apoptosis could be enhanced by farnesol inhibition
      of PLD signal transduction. Whereas it was shown that highly invasive cancer cell
      line depends on PLD activity for survival when deprived of serum growth factors.
      Based on these reports, it is postulated that apoptosis in the cerebellum and
      brainstem induced after focal cerebral HI treatment may be caused by faulty PLD
      expression. This is consistent with a report that PLD1 activity and mRNA levels
      were down-regulated during apoptosis. To test this hypothesis, Northern blotting
      was used to examine PLD2 mRNA expression after focal cerebral HI. The results
      show that both PLD2 mRNA 10.8 and 3.9 kb transcripts were significantly decreased
      by as much as 37% in the brainstem and cerebellum areas 3 h after HI compared to
      the control, concur with previous report of decreasing PLD activity after
      ischemia. These PLD2 transcripts, however, were not significantly different from
      the control 3 days after HI, indicating that the decrease in PLD2 transcription
      after HI maybe a transient phenomenon. This is the first report to show that the
      loss of membrane integrity resulting from deprivation of energy and growth
      factors after HI could cause decrease in PLD2 transcription that promotes
      apoptosis. The hypothetic role of PLD2 and the mechanism leading to apoptosis
      remains to be further elucidated.

PMID- 17024568
TI  - Mitochondrial regulation of neuronal plasticity.
AB  - The structure and function of neurons is dynamic during development and in
      adaptive responses of the adult nervous system to environmental demands. The
      mechanisms that regulate neuronal plasticity are poorly understood, but are
      believed to involve neurotransmitter and neurotrophic factor signaling pathways.
      In the present article, I review emerging evidence that mitochondria play
      important roles in regulating developmental and adult neuroplasticity. In
      neurons, mitochondria are located in axons, dendrites, growth cones and pre- and
      post-synaptic terminals where their movements and functions are regulated by
      local signals such as neurotrophic factors and calcium influx. Mitochondria play
      important roles in fundamental developmental processes including the
      establishment of axonal polarity and the regulation of neurite outgrowth, and are
      also involved in synaptic plasticity in the mature nervous system. Abnormalities
      in mitochondria are associated with neurodegenerative and psychiatric disorders,
      suggesting a therapeutic potential for approaches that target mitochondrial
      mechanisms.

PMID- 17024569
TI  - Minireview: expression and function of golli protein in immune system.
AB  - In this minireview, the author briefly reviews the development of our
      understanding on the immunological function of golli proteins. In the immune
      system, in addition to serving as autoantigens, golli proteins have been recently
      found to regulate T-cell activation directly, thus modulating EAE induction. The
      evidence that golli proteins function as signal molecules is summarized.

PMID- 17024570
TI  - Inhibition of nitric oxide synthase with 7-nitroindazole does not modify early
      metabolic recovery following focal cerebral ischemia in rats.
AB  - Nitric oxide has been strongly implicated in the development of tissue infarction
      in response to focal cerebral ischemia. Nitric oxide and its derivatives can
      inhibit components of the electron transport chain, providing a likely target for
      these substances in ischemic and post-ischemic brain. Lactate content is
      increased during post-ischemic reperfusion in tissue destined to become
      infarcted, consistent with impairment of mitochondrial respiration. To
      investigate the possible involvement of nitric oxide in generating these changes,
      we have tested the effect of 7-nitroindazole, a nitric oxide synthase (NOS)
      inhibitor, on the content of lactate and other metabolites during early
      reperfusion following temporary focal ischemia. This treatment inhibited total
      NOS by approximately 50%. However, the treatment did not significantly affect the
      marked increases in lactate in post-ischemic brain nor did it alter the recovery
      of other energy-related metabolites. These findings indicate that inhibition of
      oxidative metabolism is probably not the primary site of the deleterious effects
      of nitric oxide and derivatives during early post-ischemic reperfusion.

PMID- 17024571
TI  - Cryoablation versus radiofrequency ablation in the treatment of atrial flutter
      trial (CRAAFT).
AB  - INTRODUCTION: Atrial flutter is frequently treated with radiofrequency (RF)
      ablation with excellent results. While RF ablation remains the gold standard for
      catheter based treatment of atrial flutter, cryoablation has potential advantages
      including painless ablation and cryoadherence to the myocardium. We performed a
      prospective randomised trial comparing cryoablation and RF ablation in the
      treatment of atrial flutter. METHODS AND RESULTS: We randomised 32 consecutive
      patients with typical atrial flutter to either radiofrequency ablation using an 8
      mm tip Blazer II XP catheter (EP Technology, San Jose, USA) or cryoablation using
      a 9 French 8 mm tip Freezor Max catheter (CryoCath Technologies Inc, Kirkland,
      QU, Canada). Twenty eight patients were then followed up for a mean of 14.7
      months. The procedure was successful in producing isthmus block in all but one
      patient in the cryoablation group. Cryoablation was associated with a
      significantly longer procedure (171 vs 99 min) and ablation duration (59 vs 12.7
      min), however fluoroscopy exposure was similar (30 vs 29 min). Cryoablation was
      associated with reduced pain scores compared with RF (mean pain score 0.4 vs
      3.5). There were two recurrences of atrial flutter during follow-up, both in the
      cryoablation group. CONCLUSIONS: Cryoablation has improved patient tolerability
      compared to RF ablation, however is associated with longer procedure and ablation
      durations. Further trials are required to confirm whether cryoablation has
      similar acute and chronic efficacy to RF ablation.

PMID- 17024572
TI  - Consequences of living-donor liver transplantation for upper gastrointestinal
      lesions: high incidence of reflux esophagitis.
AB  - There is little information available regarding the consequences of living-donor
      liver transplantation (LDLT) for upper gastrointestinal lesions. We
      retrospectively compared the pre- and posttransplant incidences of noninfectious
      reflux esophagitis, portal hypertensive gastropathy (PHG), esophageal varix,
      gastroduodenal ulcer, Helicobacter pylori infection, and abnormal
      gastroesophageal valve in 29 adult patients (16 males, 13 females) who underwent
      LDLT for end-stage liver disease. Here we present four findings from this study.
      First, the posttransplant incidence of noninfectious esophagitis was
      significantly higher than the pretransplant incidence (27.6% vs. 3.4%; P <
      0.001), irrespective of postoperative use of standard-dose H2RA. Second, PHG and
      esophageal varix, which were noted in 65.5% and 96.6% of pretransplant
      recipients, respectively, spontaneously resolved postoperatively in all cases.
      Third, H. pylori infection, which was observed in 50.0% of preoperative
      recipients, decreased to 5.6% postoperatively, although no significant difference
      was observed between the pre- and the posttransplant incidences of gastroduodenal
      ulcer (6.9% vs. 6.9%). Finally, the incidence of abnormal gastroesophageal valve
      did not change following LDLT (34.5% vs. 34.5%). In conclusion, this study
      suggests that noninfectious reflux esophagitis occurs more frequently following
      LDLT. Although the disease is the results of a very complex interaction of
      various factors, spontaneous resolution of PHG and serendipitous H. pylori
      eradication might have contributed to increased incidence of postoperative
      esophagitis, possibly through gastric acid hypersecretion. In contrast,
      morphological change of the gastroesophageal valve was not considered to be the
      cause of this disease. Because this study was a retrospective analysis of a small
      population of LDLT recipients, prospective randomized controlled studies of a
      sufficient number of cases are required to substantiate these conclusions.

PMID- 17024573
TI  - Uninvestigated dyspepsia in Latin America: a population-based study.
AB  - We sought to assess the prevalence, severity of symptoms, and risk factors of
      uninvestigated dyspepsia in a population-based study in Argentina. Eight hundred
      thirty-nine valid questionnaires were evaluated. Dyspepsia was present in 367
      subjects (43.2%; 95% confidence interval [CI], 39.8-46.6); 110 (13.6%) had
      overlap with gastroesophageal reflux disease (GERD). The group with dyspepsia
      without GERD consisted of 257 subjects (29.6%; 95% CI, 26.5-32.7), 183 (71.1%)
      had ulcer-like dyspepsia, and 74 (28.9%) had dysmotility-like dyspepsia. Symptoms
      were considered very severe in 1.9%, severe in 14.0%, moderate in 59.5%, and mild
      in 24.5% of the subjects. Dyspepsia was associated with a score >14 on the
      psychosomatic symptom scale (PSC) (OR, 2.52; 95% CI, 1.75-3.61), a family history
      of diseases of the esophagus or stomach (OR, 1.73; 95% CI, 1.19-2.52) and an
      educational level >12 years (OR, 1.55; 95% CI, 1.05-2.29). Dyspepsia is
      especially prevalent in Argentina. In a significant proportion of dyspeptic
      subjects, the severity of symptoms interferes with daily activities. A higher
      PSC, positive family history, and a higher educational level are risk factors for
      dyspepsia.

PMID- 17024574
TI  - ICAM-1 signal transduction in cells stimulated with neutrophil elastase.
AB  - Neutrophil elastase, which enhances intercellular adhesion molecule-1 (ICAM-1)
      expression in endothelial cells, plays an important role in ischemia/reperfusion
      injury. Here, we investigated signal transduction of ICAM-1 expression in
      endothelial cells stimulated by neutrophil elastase. Pretreatment of animals with
      the neutrophil elastase inhibitor, ONO-5046.Na significantly decreased the number
      of neutrophils or Mac-1(+) (CD11b/CD18) cells in ischemic liver lobes after
      reperfusion. ICAM-1 expression in the rat endothelial cell line (WK-5) was
      significantly upregulated after stimulation with neutrophil elastase, but this
      reaction was inhibited by the neutrophil elastase inhibitor ONO-5046.Na. ICAM-1
      mRNA expression, which is induced by neutrophil elastase in a dose-dependent
      manner, was repressed by the alpha1-protease inhibitor. ICAM-1 expression,
      stimulated by neutrophil elastase, was partially reduced by a diacylglycerol
      kinase inhibitor and protein kinase C inhibitor, but was completely inhibited by
      a phospholipase C inhibitor, cytosolic Ca(2+) chelator, calmodulin antagonist,
      and nuclear transcription factor kappa B inhibitor. Binding of (125)I-neutrophil
      elastase to WK-5 cells was competitively inhibited by the addition of unlabeled
      neutrophil elastase. The neutrophil elastase inhibitor significantly reduces ICAM
      1 expression and Mac-1(+) cell accumulation in ischemic liver lobes after
      reperfusion. Neutrophil elastase stimulates ICAM-1 expression in endothelial
      cells by intracellular signal transduction via activation of diacylglycerol
      kinase, protein kinase C, phospholipase C, Ca(2+)-calmodulin, and nuclear
      transcription factor kappa B.

PMID- 17024575
TI  - Cytotoxic activity of Apomine is due to a novel membrane-mediated cytolytic
      mechanism independent of apoptosis in the A375 human melanoma cell line.
AB  - Apomine, a novel bisphosphonate ester, has demonstrated anticancer activity in a
      variety of cancer cell lines; however, its mechanism of cytotoxicity is not well
      understood. Previous work has demonstrated that Apomine induces cell death by
      activation of caspase-3 in several cancer cell types. However, we have
      demonstrated that Apomine induces cell death in the A375 human melanoma cell line
      through a novel membrane-mediated mechanism that is independent of caspase-3
      activation. This mechanism of membrane lysis may apply to other bisphosphonates
      and may be an important mechanism for overcoming resistance to apoptosis.
      Interestingly, Apomine-mediated cell death in the A375 and UACC 3093 human
      melanoma cell lines is also independent of N-Ras farnesylation, which was a
      previously described mechanism of action for Apomine in other cancer cell types.
      These data suggest that Apomine induces cell death through a novel plasma
      membrane-mediated cytolytic pathway, independent of caspase-3 activation and N
      Ras farnesylation.

PMID- 17024576
TI  - Process and outcome evaluation of an emergency department intervention for
      persons with mental health concerns using a population health approach.
AB  - PURPOSE: To evaluate an emergency department's use of a mental health triage and
      mental health crisis counsellor for persons presenting with mental health
      concerns. METHOD: Mixed method (qualitative and quantitative), multiple measures.
      RESULTS: Significant pre- and post-intervention reductions for wait time,
      security incidents and hospital admissions were found. Follow ups with a
      community agency, medications and a psychiatrist increased post-intervention,
      while follow ups with detox decreased post-intervention. CONCLUSIONS: The
      qualitative and quantitative findings are congruent with other studies supporting
      the use of properly implemented mental health triage and crisis counsellors to
      improve the care of persons with mental health concerns.

PMID- 17024577
TI  - Stress among family caregivers of older persons in Singapore.
AB  - It is projected that, in the 21st century, the majority of the world's older
      people will be living in Asia. After Japan, Singapore is the most rapidly aging
      country in Asia. With an increasing life expectancy, many older persons will
      require health and instrumental care during later life stages. In Singapore,
      close to 95% of older people co-reside with family members, highlighting the
      importance of community support for family caregivers. Using a study of 61
      principal family caregivers in Singapore, this article highlights the nature of
      and relationship between caregivers' stress and gender, patients' activities of
      daily living (ADL) and instrumental ADL dependency, and caregivers' attitudes.
      Findings from the study suggest that female caregivers tended to be more stressed
      than male caregivers. Results also showed a significant inverse relationship
      between the level of stress experienced by caregivers and the ADL and
      instrumental ADL dependency of patients. Caregivers looking after patients
      suffering from dementia, Parkinson's disease, and hypertension were more likely
      to be stressed than those caring for persons with stroke, depression, and other
      illnesses. This article concludes by describing some implications of this
      research for social worker practice and for informal as well as formal support
      programs for family caregivers.

PMID- 17024578
TI  - [Did quality of life research achieve its aim?].

PMID- 17024579
TI  - [For and against: is quality of life a meaningful indicator of outcome? For].

PMID- 17024580
TI  - [Possibilities and limitations of the use of quality of life as outcome-indicator
      in schizophrenic patients].
AB  - OBJECTIVE: A systematic review on empirical results of studies that assess
      Quality of Life (QoL) in schizophrenic patients. METHOD: A systematic overview of
      the literature is provided with focus on schizophrenic patients under deprived
      living conditions. RESULTS: No consistent relationships are found between
      objective living conditions and their subjective evaluation by means of QoL
      ratings. The latter are influenced by the level of depression, personality
      factors and adaptation. CONCLUSIONS: Objective and subjective variables represent
      distinct latent constructs. Standards for the use of subjective QoL as outcome
      indicator are suggested.

PMID- 17024581
TI  - [Quality of life, social deprivation and mental disorders--is there an
      association in populations at risk?].
AB  - OBJECTIVE: The study aims at assessing the psychiatric morbidity and the quality
      of life of persons at immediate risk for getting homeless as well as identifying
      risk factors and correlations between quality of life, threatening homelessness
      and mental disorders. METHODS: The sample included 101 citizens of Mannheim,
      Germany, which were immediately threatened to be thrown out of their apartment
      due to not paying their rent or other causes. In a cross-sectional study, mental
      disorders were diagnosed by SKID-interview, quality of life was determined by
      using the Munchener Lebensqualitats-Dimensionen Liste (MLDL). Other factors of
      potential influence were assessed. Multiple regression analyses were conducted.
      RESULTS: Acute mental disorders requiring treatment were determined in 79,3 % of
      the study sample. Addiction disorders (alcoholism) played a major role. This
      psychiatric morbidity was even higher in some disorders than in a sample of
      homeless people from the same region. Quality of life was low and also showed a
      similar pattern to the homeless sample. Regression analyses confirmed a high
      association of mental disorders and quality of life, which was adversely affected
      by former episodes of homelessness, the length of instable social conditions and
      a lack of social support. CONCLUSIONS: Specific psychiatric services or programs
      for the population at risk were not available, although their help seeking
      behaviour offers good opportunities for taking primary or secondary preventive
      action, which is likely to reduce the subjective burden on quality of life and
      lower the payments provided by local welfare agencies.

PMID- 17024582
TI  - [Discriminative ability, construct validity and sensitivity to change of the EQ
      5D quality of life questionnaire in paranoid schizophrenia].
AB  - OBJECTIVE: To analyze the discriminative ability, construct validity and
      sensitivity to change of the EQ-5D in paranoid schizophrenia (ICD-10 F20.0).
      METHODS: Data of 408 patients was analyzed in a longitudinal study by comparing
      EQ-5D with SF-36, CGI-S, PANSS, and GAF. RESULTS: EQ-5D showed considerable
      discriminative ability in the patient sample when compared to a representative
      population sample. If a measure used for comparison and a EQ-5D dimension were
      theoretically corresponding, the measure's mean score differed significantly
      between EQ-5D answer levels, with largest effect sizes for SF-36 scales
      (0.34<|d|<1.76), but rather small values for CGI-S, PANSS and GAF (|d|<0.5). EQ
      5D VAS (mean 61.3) and German EQ-5D index (mean 0.84) showed rather moderate
      correlations with most other scales (0.18<|r|<0.62). ROC-analysis indicated a
      very low sensitivity to change of EQ VAS and German EQ-5D index (0.50<AUC<0.58).
      CONCLUSIONS: Although focusing on physical problems, the EQ-5D seems to have
      reasonable discriminative ability and construct validity, but very low
      sensitivity to change.

PMID- 17024583
TI  - [Schizophrenic patients' quality of life--association with coping, locus of
      control, subjective well-being, satisfaction and patient-judged caregiver
      burden].
AB  - OBJECTIVE: The interrelation of subjective concepts to quality of life has been
      mainly separately explored so far. METHODS: Beside quality of life (WHOQOL-BREF)
      of 117 schizophrenic inpatients coping (FKV-LIS), locus of control (KKG),
      subjective well-being under medication (SWN-K), patient satisfaction (ZUF-8),
      caregiver burden (FBA) as well as sociodemographic and disease-related variables
      (German Basic Documentation System, BADO) were analysed using Pearsonian
      correlation and regression analyses. RESULTS: Predictors of quality of life were
      physical well-being, social and occupational integration, active problem-focused
      coping, less minimization of illness, voluntary admission to hospital, high
      satisfaction with treatment and life, being aware of positive changes as a
      consequence of illness and low-rated caregiver burden. In contrast, locus of
      control, sociodemographic and disease-related variables as well as medication
      (conventional or atypical antipsychotics) had no significant influence.
      CONCLUSIONS: Active problem-focused coping, social and occupational integration
      and physical well-being play an important role for schizophrenic patients'
      quality of life and should be considered in treatment regimens.

PMID- 17024584
TI  - [Concepts of quality of life in patients with schizophrenia. The relationship to
      their quantitative evaluation of quality of life].
AB  - OBJECTIVE: It is analysed whether the personal concept of what constitutes one's
      quality-of-life (QoL) is related to subjective QoL ratings in schizophrenic
      persons. METHODS: In a cross-sectional study, statements of specific QoL-aspects
      in an open-ended interview with n=255 schizophrenic persons were correlated with
      subjective QoL ratings (Munich Quality of Life Dimensions List) and analysed for
      their predictive value by means of linear regression analysis. RESULTS: Stating
      the family and oral needs were positive, stating aspects of illness and negative
      well-being were negative predictors of subjective QoL, independent of age and
      gender. Substantial contributions to subjective QoL ratings were found when
      persons generally negated positive or, independently, generally negated negative
      aspects of QoL. CONCLUSIONS: The importance of a primary social network (family),
      of the illness and well-being for subjective QoL ratings could be replicated. It
      could be shown that "oral needs" are related to subjective QoL ratings. Moreover,
      there is further evidence for a resigning attitude towards life in schizophrenic
      persons and their impact on QoL ratings.

PMID- 17024585
TI  - [Subjective quality of life of patients with obsessive-compulsive disorder
      compared to the general population].
AB  - BACKGROUND: Patients with obsessive-compulsive disorder (OCD) not only suffer
      from obsessive-compulsive symptoms, but also the disorder is associated with
      impaired social functioning, which impact their everyday life negatively.
      OBJECTIVE: Subjective quality of life (QoL) in patients with OCD was examined and
      compared to the general German population. METHODS: 75 patients with OCD (ICD-10
      F42.0-F42.2) were recruited from the outpatient clinic for anxiety disorders at
      the Department of Psychiatry of the University of Leipzig. Patients showing
      psychiatric co-morbidity were excluded. By means of the WHOQOL-BREF, QoL was
      assessed in patients with OCD and in a sample of the general population of
      Saxony/Germany. RESULTS: Compared with the general population, QoL in patients
      with obsessive-compulsive disorders was lower in all domains of the WHOQOL-BREF.
      CONCLUSION: OCD has a substantial adverse effect on patients' subjective QoL.
      Therefore, it will be necessary to include interventions in the treatment of OCD
      aimed at improving residual deficits in psychosocial functioning and QoL.

PMID- 17024588
TI  - Boswellic acids in chronic inflammatory diseases.
AB  - Oleogum resins from BOSWELLIA species are used in traditional medicine in India
      and African countries for the treatment of a variety of diseases. Animal
      experiments showed anti-inflammatory activity of the extract. The mechanism of
      this action is due to some boswellic acids. It is different from that of NSAID
      and is related to components of the immune system. The most evident action is the
      inhibition of 5-lipoxygenase. However, other factors such as cytokines
      (interleukins and TNF-alpha) and the complement system are also candidates.
      Moreover, leukocyte elastase and oxygen radicals are targets. Clinical studies,
      so far with pilot character, suggest efficacy in some autoimmune diseases
      including rheumatoid arthritis, Crohn's disease, ulcerative colitis and bronchial
      asthma. Side effects are not severe when compared to modern drugs used for the
      treatment of these diseases.

PMID- 17024589
TI  - Plant phenolics inhibit neutrophil elastase.
AB  - Human neutrophil elastase (HNE) is a serine protease, which is present in its
      active form in inflamed tissue as well as in psoriatic lesions. In extension of
      our research on natural compounds as inhibitors of HNE or of its release, several
      phenolics of different size were tested. The ellagitannins agrimoniin and
      pedunculagin were the most potent direct HNE inhibitors (IC (50) = 0.9 and 2.8
      microM, respectively). Ligand docking calculations provided evidence that
      inhibition may occur in an unspecific manner. Agrimoniin also showed anti
      proliferative effects in the ATP assay (IC (50) = 3.2 microM), suggesting that
      this type of tannin could have beneficial effects in the treatment of diseases
      such as psoriasis. Tests with other phenolics combined with ligand docking
      experiments revealed that, besides the presence of ORTHO-dihydroxy groups, a
      specific lipophilic shape is necessary for an inhibitory activity. The phenolic
      genistein deserves special interest as an inhibitor of elastase release because
      its effect was remarkably potent (IC (50) = 0.6 microM).

PMID- 17024590
TI  - Development of in vitro techniques for the important medicinal plant Veratrum
      californicum.
AB  - VERATRUM CALIFORNICUM (Liliaceae) is an important monocotyledonous medicinal
      plant which is the only source of the anticancer compound cyclopamine. An IN
      VITRO culture system for somatic embryogenesis and green plant regeneration of
      VERATRUM CALIFORNICUM was developed. Embryogenic calli were induced from mature
      embryos on induction medium. Five basal media supplemented with different growth
      regulators were evaluated for embryogenic callus induction, modified MS medium
      with 4 mg/L picloram showing the best result for embryogenic callus production.
      Fine suspension cell lines were established by employing friable embryogenic
      calli as starting material and AA medium and L2 medium as culture media. The
      suspension cell lines cultured in AA medium with 4 mg/L NAA appeared to be fresh
      yellow and fast growing. The suspension cells were cryopreserved successfully and
      recovered at a high rate. Green plants were regenerated from embryogenic calli
      maintained on solid medium with 73 % regeneration ability (green plants/100
      calli) in 27-month-old culture. The IN VITRO plantlets contained the steroid
      alkaloids cyclopamine and veratramine. This IN VITRO system will form the basis
      for metabolic engineering of VERATRUM cells in the context of biotechnological
      production of pharmaceutically important secondary metabolites. DMSO:dimethyl
      sulfoxide fw:fresh weight NAA:naphthaleneacetic acid 2,4-D:2,4
      dichlorophenoxyacetic acid picloram:4-amino-3,5,6-trichloro-2-pyridinecarboxylic
      acid dicamba:3,6-dichloro-2-methoxybenzoic acid.

PMID- 17024592
TI  - Epidemiology and risk factors of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common disorder that can affect apparently
      healthy as well as hospitalized patients. The actual incidence and prevalence of
      this disease are difficult to estimate because of its often silent nature. The
      clinical relevance of VTE is highlighted by the important rates of recurrence and
      mortality. The individual risk of VTE varies as a result of a complex interaction
      between congenital and transient or permanent acquired risk factors. Risk factors
      can be either intrinsic (e.g., age, obesity, history of VTE, or thrombophilia) or
      disease related (e.g., surgical procedures and medical disorders such as cancer,
      heart failure, or acute respiratory failure). The presence or absence of specific
      risk factors may play an important role in decisions about the type (and
      duration) of thromboprophylaxis/anticoagulation to be used.

PMID- 17024593
TI  - Diagnosis of deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) requires a prompt and accurate diagnosis to avoid the
      potentially fatal consequences of a delay in adequate treatment. The diagnostic
      strategy of suspected venous thromboembolism is an example of the application of
      Bayes' theorem. As a result, the available diagnostic tools, both noninvasive
      (such as ultrasonography, D-dimer, and computed tomography) and invasive (such as
      venography), are usually integrated in diagnostic strategies that require the
      evaluation of the a priori clinical probability of disease (pretest probability).
      These strategies also vary according to the patient characteristics that allow
      the definition of five different categories: symptomatic outpatients, symptomatic
      inpatients, high-risk asymptomatic subjects, patients with suspected recurrence,
      and pregnant women. Some areas are still a matter of debate, such as the clinical
      relevance of isolated distal DVT and the diagnosis of suspected ipsilateral
      recurrence.

PMID- 17024594
TI  - The value of clinical findings and D-dimer tests in diagnosing deep vein
      thrombosis in primary care.
AB  - In primary care, the physician has to decide which patients with a suspicion of
      deep vein thrombosis (DVT) have to be referred for further diagnostic work-up.
      Accurate referral is of utmost importance because unrecognized and therefore
      untreated DVT may cause pulmonary embolism. The classic clinical findings are not
      sufficiently accurate for the diagnosis of DVT. The majority of the referred
      patients, 70 to 80%, do not have DVT and this puts a burden on both patients and
      health care budgets. Diagnosis in primary care is different from that in
      secondary care caused by the referral mechanism or spectrum difference.
      Diagnostic tests derived in secondary care, therefore, cannot simply be
      generalized to primary-care patients. The well-known diagnostic rule for DVT, the
      Wells rule, does not adequately rule out DVT in primary-care patients. A proper
      diagnostic rule for use in primary care is lacking; therefore, we investigated
      the data of 1,295 patients in primary care suspected of having DVT. We developed
      and validated a simple diagnostic decision rule to exclude the presence of DVT
      safely in primary care. Independent diagnostic indicators of the presence of DVT
      were male gender, oral contraceptive use, presence of malignancy, recent surgery,
      absence of leg trauma, vein distension, calf circumference difference, and D
      dimer test result. Application of this rule could reduce the number of referrals
      by at least 23%, whereas only 0.7% of the patients with a DVT would not be
      referred. A diagnosis strategy is given, together with a practical flow diagram.

PMID- 17024595
TI  - Different accuracies of rapid enzyme-linked immunosorbent, turbidimetric, and
      agglutination D-dimer assays for thrombosis exclusion: impact on diagnostic work
      ups of outpatients with suspected deep vein thrombosis and pulmonary embolism.
AB  - The requirement for a safe diagnostic strategy should be based on an overall
      posttest incidence of venous thromboembolism (VTE) of less than 1%, with a
      negative predictive value of more than 99 to 100% during 3-month follow-up.
      Compression ultrasonography (CUS) and spiral computed tomography (CT) currently
      are the methods of choice to confirm or rule out deep venous thrombosis (DVT) and
      pulmonary embolism (PE), respectively. CUS has a negative predictive value (NPV)
      of 97 to 98%, indicating the need to improve the diagnostic work-up of patients
      with suspected DVT by clinical score assessment and D-dimer testing. Spiral CT as
      a stand-alone method detects all clinically relevant PEs and a large number of
      alternative diagnoses. It rules out PE with a NPV of 98 to 99%. Spiral CT is
      expensive, emphasizing the need to improve the diagnostic work-up of patients
      with suspected PE by the use of clinical score assessment and D-dimer testing.
      Clinical score assessment for DVT and PE has not safely ruled out VTE in
      multicenter studies and in routine daily practices. Modification of the Wells
      clinical score assessment for DVT by elimination of the "minus 2 points" for
      alternative diagnosis will improve the reproducibility of the clinical score
      assessment. The combination of a first negative CUS and a negative SimpliRed or
      an enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer of < 1,000 ng/mL
      safely exclude DVT (NPV > 99%) irrespective of clinical score assessment and
      without the need to repeat CUS in approximately 60 to 70% of patients. The rapid
      quantitative and qualitative agglutination D-dimer assays for the exclusion of
      VTE are not sensitive enough as stand-alone tests and should be used in
      combination with clinical score assessment. A normal rapid ELISA VIDAS D-dimer
      test as a stand-alone test safely excludes DVT and PE, with a NPV of 99 to 100%,
      irrespective of clinical score, without the need of CUS or spiral CT. The
      combined strategy of a rapid ELISA VIDAS D-dimer followed by objective testing
      with CUS for DVT and by spiral CT for PE will reduce the need for noninvasive
      imaging techniques by 40 to 50%.

PMID- 17024596
TI  - Cancer and venous thromboembolism.
AB  - The evidence of the important two-way clinical correlation between cancer and
      venous thromboembolism (VTE) dates back to Trousseau's time. Over time it has
      been established that cancer patients not only exhibit a higher risk of
      developing VTE when compared with noncancer patients, but also that VTE,
      especially in its idiopathic presentation, sometimes acts as an epiphenomenon of
      a hidden cancer, offering possible chances for anticipated diagnosis of the
      pathology. Research has contributed greatly to the progression of this field
      through the identification of VTE risk factors in this setting, and through the
      assessment of the most adequate thromboprophylaxis and treatment modalities as
      well as secondary prophylaxis management. Anticoagulant drugs appear to be an
      attractive strategy in cancer treatment because there is growing evidence for
      their possible benefits in terms of cancer prognosis and patient survival.

PMID- 17024597
TI  - Inherited thrombophilia and venous thromboembolism.
AB  - The term thrombophilia includes any inherited and acquired disorders associated
      with an increased tendency to venous thromboembolism (VTE). Inherited
      thrombophilia is one of the main determinants of VTE, and the presence of
      inherited thrombophilic defects exposed carriers to increased risks for VTE
      compared with noncarriers. There is no clear relationship between clinical
      manifestations and the type of underlying thrombophilic defect. Thus, the
      diagnosis of inherited thrombophilia has to be established on a laboratory basis.
      Carriers of thrombophilic defects may experience thrombosis at a younger age than
      noncarriers. However, a first thrombotic manifestation that occurs late in life
      may also be an expression of thrombophilia and this remains in many cases the
      only etiopathogenetic explanation for the event. Screening of family members of
      symptomatic probands has the potential to identify still asymptomatic carriers
      who may benefit from more appropriate thromboprophylaxis during high-risk
      situations for VTE. Women of fertile age who belong to these thrombophilic
      families might receive the greatest advantage from screening. Many inherited
      thrombophilic disorders can be considered risk factors for recurrent VTE,
      especially if more than one defect is present in the same patient. More intensive
      or prolonged duration of VTE treatment might be requested for the prevention of
      recurrent VTE in the most severe thrombophilic conditions. The availability of
      new methods for the assessment of thrombin generation in terms of endogenous
      thrombin potential are very promising tools for the identification of those
      carriers of inherited thrombophilia who will develop thrombosis or who will
      encounter recurrence of VTE.

PMID- 17024598
TI  - Thromboembolism in women.
AB  - Venous thromboembolism (VTE) occurs in one of every 1,000 individuals per year.
      The incidence is much lower in young persons. In persons younger than age 45, the
      incidence is one of every 10,000 individuals per year. VTE is a multifactorial
      disease due to the interaction of various risk factors that can be genetic (e.g.,
      inherited thrombophilia), acquired (e.g., age, neoplastic or autoimmune diseases,
      antiphospholipid antibodies), or transient (e.g., surgical interventions,
      fractures, trauma, prolonged immobilization). VTE is found equally in the two
      sexes. There are other transient risk factors for VTE that are typical for
      females, and these render women more exposed than men to the risk of the disease
      during their lifetime. Such risk factors are encountered frequently in a woman's
      life; they are oral contraceptive (OC) use, hormone replacement therapy, and
      pregnancy/puerperium. Moreover, various obstetric complications have attributed
      at least in part to an impaired placental circulation, suggesting a thrombosis
      theory as their common basis. In this review, the relationship between VTE and
      risk factors specifically of women is discussed, also in relation to coagulation
      abnormalities causing inherited thrombophilia.

PMID- 17024599
TI  - Hyperhomocysteinemia and venous thromboembolism.
AB  - Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic
      conversion of methionine, which is dependent on vitamins (folic acid, B12 and B6)
      as cofactors or cosubstrates. Severe hyperhomocysteinemia (homocystinuria), due
      to inherited metabolic defects of Hcy metabolism, is associated with very high
      risk of venous thromboembolism (VTE); treatment with vitamins is associated with
      dramatic decrease of VTE risk. Several case-control and prospective studies
      showed that also mild/moderate hyperhomocysteinemia (which is caused by the
      interaction of environmental factors with mild genetic abnormalities of Hcy
      metabolism) is associated with heightened risk of VTE; however, it is uncertain
      whether treatment with vitamins also decreases the VTE risk in these patients.

PMID- 17024600
TI  - Thrombosis and thrombophilia in children: a systematic review.
AB  - Thrombotic events are uncommon disorders in childhood but increasingly recognized
      due to the progress made in the understanding of the hemostasis system and the
      importance of thromboembolic disorders in children. Multiple clinical underlying
      conditions and prothrombotic disorders contribute to the development of
      thrombosis in neonates and children. In recent years programs have emerged that
      specialize in the diagnosis, prevention, and treatment of thrombosis in children.
      This review summarizes the current knowledge of the risk factors for
      thromboembolic events in the venous and arterial systems in children, the use of
      antithrombotic prophylaxis, and the role of thrombophilia. First, the clinical
      manifestations and the problems of diagnosing venous thromboembolic diseases and
      cerebrovascular diseases in children are reviewed. The prophylactic use of
      anticoagulants in children is also discussed. Unfortunately there are no large
      prospective randomized trials in children, thus guidelines are based on small
      studies or on extrapolation of data from adults. Second, the impact of
      prothrombotic defects in pediatric patients and the issue of routine testing for
      these disturbances are reviewed.

PMID- 17024601
TI  - Upper extremity deep venous thrombosis.
AB  - About 10% of all episodes of venous thrombosis are due to upper extremity deep
      vein thrombosis (UEDVT). Associated risk factors are indwelling central venous
      catheters, cancer, and coagulation defects; 20% of the episodes are unexplained.
      The onset of UEDVT is usually heralded by complaints such as arm swelling and
      pain, but may also be completely asymptomatic, especially in carriers of central
      venous lines. Objective confirmation is mandatory prior to instituting
      anticoagulation because the clinical diagnosis is unreliable; ultrasound-based
      methods represent the preferred diagnostic approach. Prophylaxis with low-dose
      heparin or low-dose warfarin may be used, especially in carriers of central
      venous catheters, although its efficacy is still uncertain. Unfractionated or low
      molecular weight heparins followed by oral anticoagulants should be regarded as
      the treatment of choice, whereas thrombolysis and surgery may be indicated in
      selected cases. Up to one third of the patients develop pulmonary embolism that
      may be fatal; postthrombotic syndrome and recurrent thromboembolism are also
      frequent complications. UEDVT should no longer be regarded as a rare and benign
      disease, as reported previously.

PMID- 17024602
TI  - Superficial vein thrombosis: risk factors, diagnosis, and treatment.
AB  - Superficial vein thrombosis (SVT) is a very common disease even though its
      incidence has never been assessed properly. Until recently, the literature on
      this topic has been relatively poor, old, and with numerous methodologic
      drawbacks, probably because this disease was considered benign and trivial.
      However, the recent recognition of a frequent association with concomitant venous
      thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE])
      and the risk of subsequent VTE complications in patients with isolated SVT has
      revived interest and has encouraged new clinical research. SVT and VTE share many
      common predisposing risk factors. Even if varicose veins represent the main cause
      of SVT, several underlying conditions (e.g., malignancy, thrombophilia,
      autoimmune diseases) should be sought, especially in idiopathic, migrant, or
      recurrent SVT of nonvaricose vein patients. The diagnosis is made in a clinical
      setting but ultrasonography is useful to identify concomitant asymptomatic DVT.
      Many medical and surgical treatments have been suggested to relieve local
      symptoms and signs, prevent recurrences, and limit the VTE risk of SVT, but the
      evidence coming from the limited number of prospective randomized studies does
      not allow strong recommendations on the optimal treatment of SVT.

PMID- 17024603
TI  - Postthrombotic syndrome.
AB  - Despite considerable progress in the diagnosis and treatment of deep vein
      thrombosis (DVT) of the lower extremities, one of every three patients will
      develop postthrombotic sequelae within 2 years; these sequelae are severe in
      approximately 20% of cases and produce considerable socioeconomic consequences.
      Among factors potentially related to the development of the postthrombotic
      syndrome (PTS) are older age, obesity, insufficient oral anticoagulant therapy,
      and recurrent ipsilateral thrombosis. Whether the extent and location of the
      initial thrombosis are associated with the development of PTS is controversial.
      Based on recent findings, the lack of vein recanalization within the first 6
      months appears to be an important predictor of PTS, whereas the development of
      transpopliteal venous reflux is not. The diagnosis of PTS can be made on clinical
      grounds for patients with a history of DVT. The combination of a standardized
      clinical evaluation with the results of compression ultrasonography and Doppler
      ultrasound helps diagnose or exclude a previous proximal vein thrombosis.
      According to the results of recent clinical studies, the prompt administration of
      adequate compression elastic stockings in patients with symptomatic DVT has the
      potential to reduce the frequency of late PTS development by half. The management
      of this condition is demanding and often frustrating. However, when carefully
      supervised and instructed to wear proper elastic stockings, more than 50% of
      patients will either remain stable or improve during long-term follow-up.
      Clinical presentation helps predict the prognosis; the outcome of patients who
      refer with initially severe manifestations is more favorable than that of
      patients whose symptoms deteriorate progressively over time.

PMID- 17024605
TI  - Wogonin inhibits IL-6-induced angiogenesis via down-regulation of VEGF and VEGFR
      1, not VEGFR-2.
AB  - So far, no antiangiogenic activity of wogonin, a flavonoid, on human umbilical
      vein endothelial cells (HUVECs) has been demonstrated. The aim of this study was
      to investigate the effects of wogonin on IL-6-induced angiogenesis in HUVEC
      cultures and chorioallantoic membrane (CAM) neovascularization. The in vivo CAM
      model was applied to evaluate the percentage of new vessel formations, followed
      by measurement of endothelial migration and tube formation in HUVEC cultures. The
      results revealed that wogonin (10(-8) approximately 10(-5)M) concentration
      dependently inhibited IL-6-induced angiogenesis. The signaling pathway was
      through down-regulation of the autocrine loop of VEGF and VEGFR-1, but not of
      VEGFR-2. Furthermore, the regulating loop of the IL-6 receptor complex was also
      attenuated via expression of sIL-6Ralpha and gp130, but not of IL-6/IL-6R binding
      density. We conclude that wogonin is a suppressive agent of the autoregulated
      loop of VEGF, VEGFR-1 and the IL-6 receptor complex.

PMID- 17024606
TI  - Pharmacokinetics, absorption and tissue distribution of tanshinone IIA solid
      dispersion.
AB  - This study was designed to elucidate the pharmacokinetics, absorption, tissue
      distribution and plasma protein binding properties of tanshinone IIA, a highly
      lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was
      isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic
      characteristics, absolute bioavailability, tissue distribution and plasma protein
      binding properties were determined. The membrane permeability was evaluated using
      Caco-2 cells in monolayer. The pharmacokinetic plasma profile of tanshinone IIA
      after a single intravenous dosing exhibited a triexponential pattern consisting
      of rapid distribution (t1/2 alpha, 0.024 h), slow redistribution (t1/2 beta, 0.34
      h) and terminal elimination phase (t1/2 gamma, 7.5 h). Tanshinone IIA
      preferentially distributed into the reticuloendothelial system, especially into
      liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %)
      bound highly to plasma proteins, among which lipoprotein played an important role
      (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute
      bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that
      the AUC and Cmax increased less proportionally to dose and Tmax was significantly
      prolonged. The poor absorption of tanshinone IIA may be caused by its low aqueous
      solubility and limited membrane permeability. There were no significant
      differences of the apparent permeability coefficient for all tested
      concentrations and for the apical to basolateral and reverse direction transport,
      suggesting a passive transport mode and no involvement of an efflux protein. In
      conclusion, tanshinone IIA has a suitable pharmacokinetic behavior except for its
      poor absorption. A pharmaceutical strategy for promoting its absorption should be
      designed to develop tanshinone IIA as a new drug candidate.

PMID- 17024608
TI  - Phytochemical study of actaea rubra and biological screenings of isolates.
AB  - A phytochemical study on the chemical constituents of the roots of Actaea rubra
      led to the isolation and characterization of eleven xylosides of 9,19
      cyclolanostane type triterpenes including the new rubraside A (1) and a beta
      sitosterol glucoside. The structures of the isolates were determined with the
      help of spectroscopic data including 2-dimensional NMR as well as comparison with
      reported data. The compounds were tested for cytotoxic, estrogenic, antioxidant,
      and anticomplement activities. They were found inactive in the tested assays,
      except for 4, which showed moderate anticomplement activity.

PMID- 17024609
TI  - [Editorial].

PMID- 17024610
TI  - [The ICF classification system--a problem oriented inventory on behalf of the
      German Society of Rehabilitation Sciences].
AB  - With the International Classification of Functioning, Disability and Health, ICF
      and its adoption by the World Health Organization in May 2001, the concept of
      "functional health" reached a new dimension. Prepared and developed further over
      many years, the concept of a comprehensive and internationally consented
      classification system completed the shifting of paradigm in our notion of disease
      and disablement, bringing along far-reaching consequences for theory and practice
      in particular in rehabilitation. Symbolizing this paradigmatic shift,
      destigmatization, resource orientation, context factors, and participation are
      among the central notions of the concept. The ICF is a foundation for seeking
      international agreement across the bounds of disciplines and is amidst an
      intensive transfer and implementation process, also in Germany. Due to the
      multitude of actors and activities involved, it has become almost impossible even
      for those taking a strong interest in the matter to keep up with developments and
      fields of applications, let alone to achieve consensus in these respects. The
      German Society of Rehabilitation Sciences therefore initiated a problem-oriented
      stocktaking of the present situation. This article seeks to point out a number of
      important developments and trends in order to provide initial orientation and
      overview. The stocktaking is intended to contribute to further disseminating the
      ICF, at the same time however to outline several crucial fields of application
      and development. To be continued and deepened, this preliminary stocktaking
      underlines several core developments along with a number of conceptual issues
      still unresolved for the time being. Notwithstanding a high degree of acceptance
      of the concepts underlying the ICF, continued and, as far as possible,
      coordinated efforts toward implementation will be required at all levels.

PMID- 17024611
TI  - [Regional quality assurance in medical rehabilitation. The Schleswig-Holstein
      Medical Rehabilitation Quality Community--main study and empirical findings from
      orthopaedic clinics].
AB  - The "Quality Community Medical Rehabilitation" (QGmR) is a voluntary association
      of several rehabilitation clinics in Schleswig-Holstein. The QGmR is closely
      oriented along the quality assurance programme of the national pension insurance
      scheme. As local initiative its emphasis lies in patient outcomes. The patients
      of the QGmR were interviewed twice (pre-post: before and four months after
      rehabilitation), and all patients were included consecutively during a defined
      period of time. After a pilot phase the main study of the QGmR was accomplished
      between 2002 and 2004. Twenty Schleswig-Holstein rehabilitation clinics with six
      diagnostic groups and a total of 3094 patients participated (2026 at both points
      of measurement). The majority of the patients interviewed were orthopaedic
      patients, and the smallest number were patients with heart disease and neurologic
      conditions. Most patients showed clearly health-related impairments before
      rehabilitation compared with population-referred data, four months after
      rehabilitation patients showed significant improvements in all health-related
      parameters. In addition to health improvement the patients showed a high
      satisfaction with all areas of the rehabilitation treatment and processes they
      were asked to judge (administration, therapy, care) independent of diagnostic
      group or rehabilitation clinic. But, also independent of diagnostic group and
      clinic, there were clear deficits in the field of post-rehabilitative treatment.
      Some of the results varied according to diagnostic group and clinic. The results
      of a comparison between the clinics showed some differences to the effect that
      some clinics were better than others, but these differences were not very large
      although statistically significant in a few cases. Nevertheless the "best" can be
      determined, which could motivate the clinics to participate in regular quality
      assurance working groups.

PMID- 17024612
TI  - [Acceptance of a psychometric routine diagnostics and quality monitoring system
      among psychotherapists in inpatient psychosomatic rehabilitation].
AB  - OBJECTIVE: Psychotherapists are considered to be sceptical of empirical measures
      of quality assurance. It is generally recognised that the success of these
      measures mainly depends on how they are accepted by the people involved. METHODS:
      The acceptance of a quality monitoring system among psychotherapists was
      investigated with a standardised assessment instrument. RESULTS: Practical
      relevance and practicability of the system were judged positively on the
      following dimensions: "support of clinical diagnostics", "examination of the
      outcome", "reflecting on the therapeutic process", "documentation", "integration
      in the therapeutic process", "pressure to succeed and control" and "work
      loading". The factors "professional experience", "profession" and "sex" had just
      a small influence on the degree of acceptance of the quality monitoring system.
      CONCLUSIONS: Psychotherapists consider a practically relevant and economical
      quality monitoring system as useful.

PMID- 17024613
TI  - [Managing urinary incontinence in stroke rehabilitation--a review].
AB  - BACKGROUND: Urinary incontinence following stroke is an extensive problem for the
      patients and their relatives that influences the well-being and care in the
      future. There are a lot of therapeutic interventions available, their
      effectiveness, however, is not known in detail. For rehabilitation practice the
      ongoing question is how Urinary Incontinence (UI) can best be treated in a way
      that the patients daily life is not compromised. METHOD: The search for clinical
      trials was carried out in PubMed, CINAHL, and Cochrane Library, restricted to
      German and English papers published between 1989 and April 2005. Medical, nursing
      and physiotherapeutic interventions for treating UI after stroke were described
      and analysed. RESULTS: The clinical trials were divided into process-oriented
      trials and those looking at individual interventions. The process trials could be
      divided into three different groups with an overall success of 82-95 %, 50-56 %
      and 23-36 % respectively. Behavioral methods (caregiver-induced, patient-active
      and other interventions) and medical interventions are available. The studies of
      the most successful group include staff education and application of
      interventions based on an assessment procedure and a guideline. No clinical trial
      on individual interventions reached a result like the process-oriented studies.
      CONCLUSION: For treating urinary incontinence a multimodal approach is necessary:
      special education of the nurses, applying and acting in a problem-solving
      process, for example in the Rehabilitation Cycle and delivering care based on an
      assessment procedure and guidelines. Development of a guideline for treating
      urinary incontinence after stroke can be recommended. Further research in the
      efficacy of individual interventions is needed.

PMID- 17024614
TI  - [Chronic fatigue in complementary rehabilitative medicine--predictors of the
      outcomes].
AB  - Chronic exhaustion and fatigue are increasingly important in rehabilitation
      medicine. Objectives of this study were (a) to describe the effects of in-patient
      rehabilitation on patients with chronic fatigue syndromes, (b) to identify
      predictors for treatment outcome, and (c) to analyze the impact of comprehensive
      diagnosing on these issues. A total of 171 patients with chronic exhaustion or
      fatigue (90 % female, mean age 55 +/- 10 yrs) from a rehabilitation hospital with
      a complementary medicine-based treatment concept were included in a prospective
      observational study. Within the longitudinal study patients were examined three
      times (on admission to hospital, at discharge as well as six months later).
      Participation rate of the postal inquiry was 69 %. Besides items constructed ad
      hoc, Patient questionnaires included the Symptom Checklist and assessment
      instruments for depression, quality of life, sense of coherence as well as for
      changes in experience and behaviour. Treatment outcome was defined as sum score
      of binary-coded response criteria. The pattern of complaints differed clearly
      between diagnostic subgroups (neurasthenia, affective disorders, adjustment
      disorders) before treatment. At discharge from hospital patients showed
      clinically relevant improvements lasting for six months after rehabilitation.
      Multiple regression analyses revealed a statistically significant relationship (R
      (mult) = 0.59) between predictors and outcome at discharge from hospital. A
      better result was associated with higher trust in treatment success, active
      information seeking on complementary medicine, healthier feeding habits, better
      somatic health and a decreased mental status, with regard to the status before
      treatment. The prediction of outcome after six months was comparably poorer (R
      (mult) = 0.42). Treatment success was higher in the absence of a diagnosis of
      neurasthenia, in patients accepting the group-oriented treatment concept and in
      patients not believing that their disease was due to their own way of living.
      Trust in the success of the treatment was a highly ranked predictor for longer
      lasting outcome, too. The results underline the importance of motivation aspects
      for treatment outcome indicating that individual expectations and attitudes
      should be considered in a more distinct way when allocating patients to
      rehabilitative programmes.

PMID- 17024615
TI  - [Rehabilitation of construction industry workers considering special workplace
      demands--results of the "RehaBau" pilot study].
AB  - In a descriptive study, 122 construction industry workers were treated in an
      especially workplace-oriented inpatient rehabilitation measure. Effects were
      assessed by written questionnaires using the SF-36 questionnaire, the
      questionnaire for employees self-assessment (FBS) and further standardized
      instruments for job strain and demand at time intervals of 0, 4 and 13 months
      from rehabilitation participation. Along with high rehabilitation satisfaction,
      improvement of quality of life and decreasing disability complaints are reported,
      which keep stable and significant for at least one year and thus are indicators
      of sustainable rehabilitation success.

PMID- 17024616
TI  - [The "personal budget"--pleading for its proactive application].

PMID- 17024617
TI  - [Standard of integration management at company level and its auditing].
AB  - SITUATION: Responsibility at company level for the employment of workers with
      health-related problems or disabilities has increased, inter alia because of
      integration management at company level according to section 84 (2) of the German
      Social Code Book IX. Although several recommendations exist, no standard is
      available for auditing and certification. Such a standard could be a basis for
      granting premiums according to section 84 (3) of Book IX of the German Social
      Code. AUDIT AND CERTIFICATION: One product of the international "disability
      management" movement is the "Consensus Based Disability Management Audit"
      (CBDMA). The Audit is a systematic and independent measurement of the
      effectiveness of integration management at company level. CBDMA goals are to give
      evidence of the quality of the integration management implemented, to identify
      opportunities for improvement and recommend appropriate corrective and preventive
      action. In May 2006, the integration management of Ford-Werke GmbH Germany with
      about 23 900 employees was audited and certified as the first company in Europe.
      STANDARD OF INTEGRATION MANAGEMENT AT COMPANY LEVEL: In dialogue with corporate
      practitioners, the international standard of CBDMA has been adapted, completed
      and verified concerning its practicability. Process orientation is the key
      approach, and the structure is similar to DIN EN ISO 9001:2000. Its structure is
      as follows: (1) management-labour responsibility (goals and objectives, program
      planning, management-labour review), (2) management of resources (disability
      manager and DM team, employees' participation, cooperation with external
      partners, infrastructure), (3) communication (internal and external public
      relations), (4) case management (identifying cases, contact, situation analysis,
      planning actions, implementing actions and monitoring, process and outcome
      evaluation), (5) analysis and improvement (analysis and program evaluation), (6)
      documentation (manual, records).

PMID- 17024618
TI  - Secular trends in the aerobic fitness test performance and body mass index of
      Korean children and adolescents (1968-2000).
AB  - There is increasing evidence that the aerobic fitness performance of children is
      declining, at least in developed countries. To see if there was evidence of
      similar trends in a non-Western country, this study analysed data on 6-18-year
      old Koreans tested between 1968 and 2000 using distance runs ranging from 600 to
      1200 m. All existing data on the results of children's aerobic fitness tests in
      Korea were collated. In addition to six individual studies, very large datasets
      were available from the Korean Ministries of Education, and the Ministry of
      Culture and Tourism. Data on a total of 22,127,265 6-18-year-old children were
      available in the form of group means and standard deviations. Data were collated
      for each age x sex x test group, and performances were expressed as percentages
      of the fitted values for the year 1992 to standardise across tests, ages and
      sexes. All age x sex x test groups were then combined, and curves were fitted
      using weighted regression. A two-linear segment model best described the pattern
      of change (r = 0.83, p < 0.001). There was a relatively slow decline (0.26 % per
      year) in the aerobic performance of Korean children between 1968 and 1984. After
      1984, however, there was a steep decline in performance, averaging 0.80 % per
      year. The rate of decline was greater in boys, younger children and children from
      outside the capital Seoul. Changes in running performance showed a similar
      pattern to changes in estimated body mass index. Compared to other countries,
      there has been a sharp decline in Korean children's performance on tests of
      aerobic fitness, which has been concurrent with increases in estimated body mass
      index.

PMID- 17024619
TI  - Hormonal responses after a strength endurance resistance exercise protocol in
      young and elderly males.
AB  - This study examined testosterone, cortisol and growth hormone responses in
      elderly and young men after a strength endurance protocol. Eight elderly (age: 69
      +/- 5 yrs) and nine young (age: 23 +/- 1 yrs) males with recreational experience
      in resistance training performed a strength endurance protocol, which included
      six exercises. At each exercise, the subjects performed 3 sets of 15 reps at 60 %
      of 1-RM with a 90 s rest interval between sets. The subjects also participated in
      a control session. Hormonal and blood lactate concentrations were measured before
      exercise, immediately after exercise and 15 min after the end of exercise. Blood
      lactate increased (p<0.05) with resistance exercise in both age groups with the
      highest increases observed in the young males. Testosterone and cortisol
      concentrations were higher (p<0.05) immediately and 15 min after exercise as
      compared to the respective control session values in both young and elderly
      subjects, whereas no differences were observed between groups (p>0.05). Growth
      hormone concentration increased (p<0.05) after resistance exercise compared to
      the control session in both age groups. This increase was higher (p<0.05) in the
      young as compared to the elderly group. The above results show that a moderate
      intensity - high repetition resistance exercise protocol for the improvement of
      strength endurance, seems to be a sufficient stimulus that increases
      testosterone, growth hormone and cortisol concentrations in elderly males. These
      hormonal responses may create an optimal metabolic environment, which improves
      muscular function after a strength endurance program although the elderly
      subjects present an attenuated growth hormone response compared to younger ones.

PMID- 17024620
TI  - Comparison of spatio-temporal, metabolic, and psychometric responses in
      recreational and highly trained swimmers during and after a 400-m freestyle swim.
AB  - Spatio-temporal, metabolic and psychometric responses during and after a 400-m
      freestyle swim trial were investigated for gender and skill-level effects. Thirty
      four men and women, 18 national and international competitors and 16 recreational
      swimmers, were compared. Mean speed, stroke rate (SR), and stroke length (SL)
      were obtained from video recordings. Peak heart rate (HR) and the lactate value
      (Hla) were determined, as were the recovery kinetics, i.e., the recovery time
      index (RTI) for heart rate and %Hla (r) for the lactate values. Well-being was
      assessed with the Profile of Mood States questionnaire (POMS). Subjective
      workload was assessed with the NASA-TLX questionnaire. The experts showed less
      variation in their swim speed than the recreational swimmers. The male experts
      showed greater SL and the female experts showed greater SL and SR. No significant
      difference was noted between the experts and recreational swimmers for peaks of
      HR and Hla, POMS (157.3 +/- 15.1 vs. 163.1 +/- 21.5), or subjective workload
      (32.4 +/- 6.7 vs. 31.6 +/- 6.1). The experts exhibited higher RTI (- 38.5 +/- 5.5
      % vs. - 31.1 +/- 5.4 %) and %Hla (r) (8.6 +/- 7.18 % vs. 1.65 +/- 8.2 %). They
      also showed an improvement of 7.8 +/- 2.6 % for men and 6.02 +/- 1.6 % for women
      between the performance time for the trial and the best competitive time of the
      season. Last, our results suggest that the 400-m freestyle trial is a valid field
      test to evaluate the maximal aerobic speed (MAS) of swimmers with different
      training status. The systemic analysis herein described can be used to set the
      end-of-season target time for expert competitors. Attention should focus on SL,
      race management, and the physiological recovery for training prescription.

PMID- 17024621
TI  - Validity of simple field tests as indicators of match-related physical
      performance in top-level professional soccer players.
AB  - The aim of this study was to examine the construct validity of selected field
      tests as indicators of match-related physical performance. During the competitive
      season, eighteen professional soccer players (age 26.2 +/- 4.5 yrs, mass 80.8 +/-
      7.8 kg, and height 181.9 +/- 3.7 cm) completed an incremental running field test
      to exhaustion, a vertical-jump and a repeated-sprint ability (RSA) test. Match
      physical performance was quantified during official matches using a video
      computerized, semi-automatic, match analysis image recognition system, (ProZone,
      Leeds, UK). The selected measures of match physical performance were: total
      distance covered (TD), high intensity running (HIR: > 14.4 km . h (-1)), very
      high intensity running (VHIR:> 19.8 km . h (-1)), sprinting (> 25.2 km . h (-1))
      and top running speed. Significant correlations were found between peak speed
      reached during the incremental field test and TD (r = 0.58, R (2) = 0.34; p <
      0.05), HIR (r = 0.65, R (2) = 0.42; p < 0.01) and VHIR (r = 0.64, R (2) = 0.41; p
      < 0.01). Significant correlations were also found between RSA mean time and VHIR
      (r = - 0.60, R (2) = 0.36; p < 0.01) and sprinting distance (r = - 0.65, R (2) =
      0.42; p < 0.01). Significant differences were found between the best and worst
      group as defined by the median split technique for peak speed (TD = 12 011 +/-
      747 m vs. 10 712 +/- 669, HIR = 3192 +/- 482 m vs. 2314 +/- 347 m, and VHIR =
      1014 +/- 120 vs. 779 +/- 122 m, respectively; p < 0.05) and RSA mean time (VHIR =
      974 +/- 162 m vs. 819 +/- 144 m, and sprinting = 235 +/- 56 vs. 164 +/- 58 m,
      respectively; p < 0.05). In conclusion, this study gives empirical support to the
      construct validity of RSA and incremental running tests as measures of match
      related physical performance in top-level professional soccer players.

PMID- 17024622
TI  - A test for evaluation of exercise with apneic episodes in synchronized swimming.
AB  - In synchronized swimming, complex maneuvers are developed in the water
      alternating air breathing and apnea episodes, which activate complex and adjusted
      mechanisms for respiratory compensation. The aim of this study is to propose a
      specific laboratory test for the assessment of the functional respiratory
      adaptations during exercise with apnea periods in synchronized swimmers. We
      studied 25 women, of which 13 were elite synchronized swimmers and the other 12
      were a control group. A laboratory test was performed on a cycle ergometer
      consisting of 4 minutes pedalling at a constant intensity of 1.5 watts/kg (test
      1). After 30 minutes at rest, a new test was performed alternating free
      respiration and apnea periods of 15 seconds at the same intensity (test 2). In
      both tests HR, VE, VT, BF, VO2, VCO2, and lactate were analyzed. We observed an
      increase in VE, VO2, and VCO2 in the 13 swimmers in test 2, with no change in HR
      and lactate, and a constant relationship between VE and VCO2 equal for tests 1
      and 2. In the control group only 6 women completed test 2, the other 6 stopped
      before the third minute. In this group, important differences were observed in
      relation to the swimmers: both heart rate and lactate increased in test 2 and
      showed an increase in the VE vs. VCO2 relationship which involved a different
      slope for test 1 and test 2. We conclude that functional respiratory adaptations
      induced by apnea during synchronized swimming are essential in this sport and the
      test proposed may be a useful tool to assess the physical performance in
      synchronized swimmers.

PMID- 17024623
TI  - Ambulatory physical activity during United States Army basic combat training.
AB  - Electronic pedometers were used to quantify locomotor physical activity during an
      entire 9-week United States Army Basic Combat Training (BCT) cycle. Pedometers
      were worn on the hips of 4 trainees in each of 10 BCT companies during all BCT
      activities. Investigators obtained pedometer readings (steps) on a daily basis,
      and estimated travel distances were obtained by multiplying steps by the average
      individual step length. A short questionnaire was administered daily to assure
      trainees wore the pedometers and trained with their companies all day. Trainees
      performed an average +/- SD of 16 311 +/- 5826 steps/day and traveled an
      estimated 11.7 +/- 4.4 kilometers/day. The highest daily locomotor activity was
      during the field training exercise in which trainees took an average +/- SD of 22
      372 +/- 12 517 steps/day traveling an estimated 16.2 +/- 9.7 kilometers/day.
      Differences among the 10 companies ranged from 14 720 +/- 6649 steps/day to 18
      729 +/- 6328 steps/day. This survey provided the first examination of locomotor
      physical activity during an entire BCT cycle.

PMID- 17024624
TI  - Time course of mechanical and neuromuscular characteristics of cyclists and
      triathletes during a fatiguing exercise.
AB  - This study examined the impact of sport specificity on the time course of fatigue
      during maximal voluntary eccentric, concentric and isometric torque production
      following a submaximal isokinetic fatiguing exercise. Seven cyclists and seven
      triathletes performed a fatiguing exercise consisting of nine sets of 31
      isokinetic concentric knee extensions at 1.05 rad . s (-1). Fatigue was assessed
      pre-exercise, after three and six sets, and post-exercise. The maximal knee
      extension torque associated with electromyographic (EMG) activity was recorded
      during voluntary contractions and electrically induced contractions (single and
      paired twitches). The maximal voluntary eccentric torque production declined in
      cyclists (18 +/- 3.5 %, p < 0.05) and was not significantly affected in
      triathletes (5 +/- 2.5 %, p > 0.05). The decrease in cyclists was associated with
      an increase in the sum of the normalized EMG (nRMS) values of the three agonist
      muscles (p < 0.01). Although no significant difference was observed between
      groups, the two-way repeated-measure analysis of variance revealed a time effect
      on maximal concentric and isometric torque, twitch contractile and
      electrophysiological response (M (max)) properties. No modification in the
      activation and coactivation levels was observed. In conclusion, these results
      indicate that the time course of fatigue, especially during eccentric
      contractions, is mediated by sport-specific adaptations likely due to the mode of
      muscle contraction used in the activity.

PMID- 17024625
TI  - The effect of music during warm-up on consecutive anaerobic performance in elite
      adolescent volleyball players.
AB  - Music is believed to improve athletic performance. The aim of the present study
      was to determine the effect of arousing music during warm-up on anaerobic
      performance in elite national level adolescent volleyball players. Twenty-four
      players (12 males and 12 females) performed the Wingate Anaerobic Test following
      a 10-minute warm-up with and without music (two separate occasions, random
      order). During warm-up with music, mean heart rate was significantly higher.
      Following the warm-up with music, peak anaerobic power was significantly higher
      in all volleyball players (10.7 +/- 0.3 vs. 11.1 +/- 0.3 Watts/kg, p < 0.05,
      without and with music, respectively). Gender did not influence the effect of
      music on peak anaerobic power. Music had no significant effect on mean anaerobic
      output or fatigue index in both genders. Music affects warm-up and may have a
      transient beneficial effect on anaerobic performance.

PMID- 17024626
TI  - Performance characteristics according to playing position in elite soccer.
AB  - The paper provides a large-scale study into the motion characteristics of top
      class soccer players, during match play, according to playing position. Three
      hundred top-class outfield soccer players were monitored during 20 Spanish
      Premier League and 10 Champions League games using a computerized match analysis
      system (Amisco Pro, Nice, France). Total distance covered in five selected
      categories of intensity, and the mean percentage of playing time spent in each
      activity were analyzed according to playing position. Midfield players covered a
      significantly greater total distance (p < 0.0001) than the groups of defenders
      and forwards did. Analyzing the different work rates showed significant
      differences (p < 0.5 - 0.0001) between the different playing positions. There
      were no significant differences between halves in the total distance covered, or
      in distances covered at submaximal and maximal intensities. However,
      significantly more distance was covered in the first half compared to the second
      in medium intensities (11.1 - 19 km/h). The current findings provide a detailed
      description of the demands placed on elite soccer players, according to their
      positional role at different work intensities, which may be helpful in the
      development of individualized training programs.

PMID- 17024627
TI  - Muscle metabolism during constant- and alternating-intensity exercise around
      critical power.
AB  - Few studies have focused on the metabolic responses to alternating high- and low
      intensity exercise and, specifically, compared these responses to those seen
      during constant-load exercise performed at the same average power output. This
      study compared muscle metabolic responses between two patterns of exercise during
      which the intensity was either constant and just below critical power (CP) or
      that oscillated above and below CP. Six trained males (mean +/- SD age 23.6 +/-
      2.6 y) completed two 30-minute bouts of cycling (alternating and constant) at an
      average intensity equal to 90 % of CP. The intensity during alternating exercise
      varied between 158 % CP and 73 % CP. Biopsy samples from the vastus lateralis
      muscle were taken before (PRE), at the midpoint and end (POST) of exercise and
      analysed for glycogen, lactate, PCr and pH. Although these metabolic variables in
      muscle changed significantly during both patterns of exercise, there were no
      significant differences (p > 0.05) between constant and alternating exercise for
      glycogen (PRE: 418.8 +/- 85 vs. 444.3 +/- 70; POST: 220.5 +/- 59 vs. 259.5 +/-
      126 mmol x kg (-1) dw), lactate (PRE: 8.5 +/- 7.7 vs. 8.5 +/- 8.3; POST: 49.9 +/-
      19.0 vs. 42.6 +/- 26.6 mmol x kg (-1) dw), phosphocreatine (PRE: 77.9 +/- 11.6
      vs. 75.7 +/- 16.9; POST: 65.8 +/- 12.1 vs. 61.2 +/- 12.7 mmol x kg (-1) dw) or pH
      (PRE: 6.99 +/- 0.12 vs. 6.99 +/- 0.08; POST: 6.86 +/- 0.13 vs. 6.85 +/- 0.06),
      respectively. There were also no significant differences in blood lactate
      responses to the two patterns of exercise. These data suggest that, when the
      average power output is similar, large variations in exercise intensity exert no
      significant effect on muscle metabolism.

PMID- 17024628
TI  - High and low volume resistance training and vascular function.
AB  - The aim was to examine the influence of high and low volume whole-body circuit
      weight training on forearm reactive hyperemic blood flow, venous capacitance and
      outflow in young individuals. Thirty-five individuals (age: 22 +/- 1.89 years)
      participated in an 8 station circuit performed 3 days/week for 5 weeks. The high
      volume group (n = 15) was encouraged to complete 3 sets/station, whereas the low
      volume group (n = 20) performed 1 set/station. Before and after training, muscle
      strength (hand grip, knee extension and bench press) and vascular function
      (reactive hyperemia, venous capacitance and outflow) were measured. Before
      training, there were no significant group differences. Training resulted in
      significant but similar strength gains in both groups (hand grip: 3.89 +/- 4.57
      kg (+ 15.59 %), knee extension: 30.62+/- 12.52 kg (+ 35.31 %), bench press: 12.4
      +/- 8.81 kg (+ 21.03 %); p < 0.05). Group averages for vascular function did not
      change following the circuit training. However, individuals with the lowest
      pretraining vascular measures did have significant increases in reactive
      hyperemic blood flow (17 %, p = 0.006) and venous outflow (18 %, p = 0.013),
      independent of group assignment. In conclusion, high and low volume circuit
      weight training results in significant and similar strength gains. Individuals
      with evidence of lower pretraining vascular function appear to respond favorably
      to short-term circuit weight training.

PMID- 17024629
TI  - Flat and uphill climb time trial performance prediction in elite amateur
      cyclists.
AB  - The aim of this study was to determine physiological, anthropometric,
      biomechanical and hormonal variables related to road flat and uphill climb
      performance. Eighteen elite level amateur road cyclists (21.1 +/- 3.8 yrs),
      homogeneous with regard to time trial performance (coefficient of variation: 2.9
      5.2 %), were measured for frontal area (FA), maximal strength, power, cross
      sectional area of the quadriceps femoris muscle and basal serum concentrations of
      total testosterone (TT), free testosterone (FT) and cortisol (C). Maximal (W
      (max)) and submaximal workload were measured during a progressive discontinuous
      maximal cycling laboratory test, and two all-out time trial performance tests
      (duration range: 1049-1251 s) were also conducted outdoors on two separate days:
      a 14-km flat road (average gradient of 0.2 %) and a 6.7-km uphill climb (average
      gradient of 6 %). Significant negative correlations (p < 0.01-0.001) were
      observed between the individuals' 14-km flat time values and the individual
      values of W (max) (r = - 0.90) and FA (r = - 0.73). Regression analysis showed
      that the individual values of the 6.7-km uphill climb trial performance time
      correlated significantly (p < 0.05-0.001) with those of FT (r = - 0.75) and W
      (max) x kg (-1) (r = - 0.66). The present results suggest that flat time trial
      performance in highly elite amateur cyclists is mainly related to absolute
      maximal workload and anthropometric variables, whereas uphill climb time trial
      performance is associated with maximal workload normalized to body mass, as well
      as with an increased anabolic-androgenic activity.

PMID- 17024630
TI  - Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young
      girls.
AB  - We compared 35 prepubertal girls, 9 artistic gymnasts and 13 rhythmic gymnasts
      with 13 nonphysically active controls to study the effect of gymnastics on bone
      and muscle mass. Lean mass, bone mineral content and areal density were measured
      by dual energy X-ray absorptiometry, and physical fitness was also assessed. The
      artistic gymnasts showed a delay in pubertal development compared to the other
      groups (p<0.05). The artistic gymnasts had a 16 and 17 % higher aerobic power and
      anaerobic capacity, while the rhythmic group had a 14 % higher anaerobic capacity
      than the controls, respectively (all p<0.05). The artistic gymnasts had higher
      lean mass (p<0.05) in the whole body and the extremities than both the rhythmic
      gymnasts and the controls. Body fat mass was 87.5 and 61.5 % higher in the
      controls than in the artistic and the rhythmic gymnasts (p<0.05). The upper
      extremity BMD was higher (p<0.05) in the artistic group compared to the other
      groups. Lean mass strongly correlated with bone mineral content (r=0.84,
      p<0.001), and multiple regression analysis showed that total lean mass explained
      64 % of the variability in whole body bone mineral content, but only 20 % in
      whole body bone mineral density. Therefore, recreational artistic gymnastic
      participation is associated with delayed pubertal development, enhanced physical
      fitness, muscle mass, and bone density in prepubertal girls, eliciting a higher
      osteogenic stimulus than rhythmic gymnastic.

PMID- 17024631
TI  - Skeletal muscle HSP expression in response to immobilization and remobilization.
AB  - Heat shock proteins play an important regulatory role in the cellular defence.
      Oxidative stress is one of the factors inducing heat shock protein expression.
      This study tested the effects of 4 weeks of immobilization and subsequent
      remobilization on heat shock protein expression and oxidative stress in the
      lateral gastrocnemius and plantaris muscles of the rat. Active mobilization or
      free mobilization protocols were used for remobilization. In active mobilization,
      strenuous uphill treadmill running, twice a day, was started immediately after
      the immobilization and lasted for six days. Rats in the free mobilization group
      moved freely in their cages immediately after the immobilization. Expression of
      heat shock proteins was upregulated during the recovery from immobilization,
      especially in the lateral gastrocnemius muscle in the active mobilization group.
      However, markers of oxidative stress, such as protein carbonyls and 4
      hydroxynonenal protein adducts, or activities of the antioxidant enzymes
      glutathione peroxidase and glutathione reductase, did not change after the
      immobilization and subsequent recovery. In summary, following immobilization,
      both intensive and spontaneous exercise upregulated the heat shock protein
      expressions in the lateral gastrocnemius muscle and partly in the plantaris
      muscle, which may contribute to the recovery from immobilization atrophy.

PMID- 17024632
TI  - Role of maximal heart rate and arterial O2 saturation on the decrement of VO2max
      in moderate acute hypoxia in trained and untrained men.
AB  - We aimed to evaluate 1) the altitude where maximal heart rate (HR (max))
      decreases significantly in both trained and untrained subjects in moderate acute
      hypoxia, and 2) if the HR (max) decrease could partly explain the drop of V.O
      (2max). Seventeen healthy males, nine trained endurance athletes (TS) and eight
      untrained individuals (US) were studied. Subjects performed incremental exercise
      tests at sea level and at 5 simulated altitudes (1000, 1500, 2500, 3500, 4500
      meters). Power output (PO), heart rate (HR), arterial oxygen saturation (SaO
      (2)), oxygen uptake (V.O (2)), arterialized blood pH and lactate were measured.
      Both groups showed a progressive reduction in V.O (2max). The decrement in HR
      (max) (DeltaHR (max)) was significant from 1000 m for TS and 2500 m for US and
      more important in TS than US (at 1500 m and 3500 m). At maximal exercise, TS had
      a greater reduction in SaO (2) (DeltaSaO (2)) at each altitude. DeltaHR (max)
      observed in TS was correlated with DeltaSaO (2). When the two groups were pooled,
      simple regressions showed that DeltaV.O (2max) was correlated with both DeltaSaO
      (2) and DeltaHR (max). However, a multiple regression analysis demonstrated that
      DeltaSaO (2) alone may account for DeltaV.O (2max). Furthermore, in spite of a
      greater reduction in SaO (2) and HR (max) in TS, no difference was evidenced in
      relative DeltaV.O (2max) between groups. Thus, in moderate acute hypoxia, the
      reduction in SaO (2) is the primary factor to explain the drop of V.O (2max) in
      trained and untrained subjects.

PMID- 17024633
TI  - Physiological determinants of time to exhaustion during intermittent treadmill
      running at vV(.-)O(2max).
AB  - Previous studies have reported large between-subject variations in the time to
      exhaustion during intermittent running at the velocity at V(.-)O (2max) (vV(.-)O
      (2max)). This study aimed to determine which physiological factors contribute to
      this variability. Thirteen male runners (age 38.9 +/- 8.7 years) each completed
      five treadmill running tests; two incremental tests to determine V(.-)O (2max),
      vV(.-)O (2max), the lactate threshold velocity (vLT) and the running velocity-
      V(.-)O (2) relationship; the third test to determine the time to exhaustion
      during continuous running at vV(.-)O (2max) (t (lim)cont); the fourth to
      determine the maximal accumulated oxygen deficit (MAOD); the fifth to determine
      the time to exhaustion during intermittent running at vV(.-)O (2max) (t
      (lim)int). Relief intervals during the intermittent test were run at 70 % vV(.-)O
      (2max). The vLT-vV(.-)O (2max) difference was significantly correlated with t
      (lim)int (r = - 0.70; p = 0.007). The correlation coefficient increased to r = -
      0.83 (p < 0.001) when the difference between the relief interval velocity and the
      vLT was deducted from the vLT-vV(.-)O (2max) difference (theoretically
      representing the net depletion of the MAOD during each work/relief interval
      cycle). The main finding of this study was that 49 % of the variance in t
      (lim)int was explained by the vLT-vV(.-)O (2max) difference, compared to 74 % for
      t (lim)cont. However, a further 20 % of unique variance in t (lim)int could be
      explained with the inclusion of the relief interval velocity-vLT difference.
      Theoretically, runners with the largest relief interval velocity-vLT difference
      will replete their anaerobic capacity to a greater extent during each relief
      interval, thereby increasing time to exhaustion.

PMID- 17024634
TI  - Exercise capacity and circulating endothelial progenitor cells in hemodialysis
      patients.
AB  - Mobilization of circulating endothelial progenitor cells (EPCs) is increased
      after acute exercise and training. This study aims to evaluate whether, in a low
      performance population, EPC levels may be related to exercise capacity in steady
      state conditions. Study population consisted of sixteen hemodialysis patients.
      The distance walked in the 6-minute walking test (6 MWD) and the maximal speed
      attained in an incremental treadmill test were used to assess the exercise
      capacity. Physical functioning was measured by the scale on the SF36
      questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration
      of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial
      growth factor receptor-2, were performed. Hemoglobin concentration, white blood
      cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides
      were measured. Statistical analysis examined the relationship between blood
      progenitors cells versus performance parameters, laboratory parameters, age, body
      mass index, hemodialysis duration, and erythropoietin therapy. Univariate
      analysis revealed a significant association between percentage values of EPC and
      performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed
      (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A
      similar statistical association between EPC absolute values and performance
      parameters was found. No correlation between CD34 (+) and any parameter under
      study was observed. Multivariate analysis indicated 6 MWD as the most significant
      independent factor associated with EPC level. EPC percentage value was
      significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the
      better performing group (6 MWD > 300 m, n=8). In a group of renal patients,
      mobilization of EPCs was related to the degree of exercise capacity, suggesting a
      possible connection with the cardiovascular risk in low performance populations
      limited by chronic diseases.

PMID- 17024635
TI  - Monitoring 6 weeks of progressive endurance training with plasma glutamine.
AB  - The distinction between positive and negative training adaptation is an important
      prerequisite in the identification of any marker for monitoring training in
      athletes. To investigate the glutamine responses to progressive endurance
      training, twenty healthy males were randomly assigned to a training group or a
      non-exercising control group. The training group performed a progressive (3 to 6
      x 90 minute sessions per week at 70 % V.O (2max)) six-week endurance training
      programme on a cycle ergometer, while the control group did not participate in
      any exercise during this period. Performance assessments (V.O (2max) and time to
      exhaustion) and resting blood samples (for haemoglobin concentration,
      haematocrit, cortisol, ferritin, creatine kinase, glutamine, uric acid and urea
      analysis) were obtained prior to the commencement of training (Pre) and at the
      end of week 2, week 4 and week 6. The training group showed significant
      improvements in time to exhaustion (p < 0.01), and V.O (2max) (p < 0.05) at all
      time points (except week 2 for V.O (2max)), while the control group performance
      measures did not change. In the training group, haemoglobin concentration and
      haematocrit were significantly lower (p < 0.01) than pretraining values at week 2
      and 4, as percentage changes in plasma volume indicated a significant (p < 0.01)
      haemodilution (+ 6 - 9 %) was present at week 2, 4 and 6. No changes were seen in
      the control group. In the training group, plasma glutamine (week 2, 4 and 6),
      creatine kinase (week 2 and 4), uric acid (week 2 and 4) and urea (week 2 and 4)
      all increased significantly from pretraining levels. No changes in cortisol or
      ferritin were found in the training group and no changes in any blood variables
      were present in the control group. Plasma glutamine was the only blood variable
      to remain significantly above pretraining (966 +/- 32 micromol . 1 (-1)) levels
      at week 6 (1176 +/- 24 micromol . 1 (-1); p < 0.05) The elevation seen here in
      glutamine levels, after 6 weeks of progressive endurance training, is in contrast
      to previous reports of decreased glutamine concentrations in overtrained
      athletes. In conclusion, 6 weeks of progressive endurance training steadily
      increased plasma glutamine levels, which may prove useful in the monitoring of
      training responses.

PMID- 17024636
TI  - Arterial stiffness and baroreflex sensitivity following bouts of aerobic and
      resistance exercise.
AB  - We examined arterial stiffness, baroreflex sensitivity (BRS), and systolic
      arterial pressure (SAP) variability after an acute bout of aerobic exercise
      compared to resistance exercise. We hypothesized that arterial stiffness would be
      reduced after aerobic exercise, while it would be increased after resistance
      exercise, and these alterations would be associated with differential changes in
      BRS and SAP variability. Arterial stiffness, BRS, and SAP variability were
      assessed before and 20 min after a bout of aerobic exercise and resistance
      exercise in 13 male participants. Pulse wave velocity (PWV) was used to measure
      central (carotid-femoral) and peripheral (femoral-dorsalis pedis) arterial
      stiffness. BRS was derived via the sequence technique. Spectral decomposition of
      beat-to-beat SAP variability was used as an estimate of sympathetic vasomotor
      tone. A mode-by-time interaction (p < 0.001) was detected for central PWV, due to
      an increase in PWV (p < 0.05) following resistance exercise and a decrease in PWV
      following aerobic exercise (p < 0.05). A mode-by-time interaction was also
      detected for peripheral PWV (p < 0.05), due to a decrease in peripheral PWV
      following aerobic exercise (p < 0.05) with no change following resistance
      exercise. BRS was significantly lower following resistance compared with aerobic
      exercise (p < 0.004). SAP variability increased following resistance exercise (p
      < 0.05) but there was no interaction. In conclusion, aerobic exercise decreased
      both central and peripheral arterial stiffness, while resistance exercise
      significantly increased central arterial stiffness only. BRS was reduced after
      both bouts of exercise, but significantly greater reductions were seen following
      resistance exercise.

PMID- 17024637
TI  - Ventilatory thresholds assessment from heart rate variability during an
      incremental exhaustive running test.
AB  - The present study examined whether the ventilatory thresholds during an
      incremental exhaustive running test could be determined using heart rate
      variability (HRV) analysis. Beat-to-beat RR interval, V(.-)O (2), V(.-)CO (2) and
      V(.-) (E) of twelve professional soccer players were collected during an
      incremental test performed on a track until exhaustion. The "smoothed pseudo
      Wigner-Ville distribution" (SPWVD) time-frequency analysis method was applied to
      the RR time series to compute the usual HRV components vs. running speed stages.
      The ventilatory equivalent method was used to assess the ventilatory thresholds
      (VT1 and VT2) from respiratory components. In addition, ventilatory thresholds
      were assessed from the instantaneous components of respiratory sinus arrhythmia
      (RSA) by two different methods: 1) from the high frequency peak of HRV ( FHF),
      and 2) from the product of the spectral power contained within the high frequency
      band (0.15 Hz to fmax) by FHF (HF x FHF) giving two thresholds: HFT1 and HFT2.
      Since the relationship between FHF and running speed was linear for all subjects,
      the VTs could not be determined from FHF. No significant differences were found
      between respective running speeds at VT1 vs. HFT1 (9.83 +/- 1.12 vs. 10.08 +/-
      1.29 km x h (-1), n.s.) nor between the respective running speeds at VT2 vs. HFT2
      (12.55 +/- 1.31 vs. 12.58 +/- 1.33 km x h (-1), n.s.). Linear regression analysis
      showed a strong correlation between VT1 vs. HFT1 (R (2) = 0.94, p < 0.001) and
      VT2 vs. HFT2 (R (2) = 0.96, p < 0.001). The Bland-Altman plot analysis reveals
      that the assessment from RSA gives an accurate estimation of the VTs, with HF x
      FHF providing a reliable index for the ventilatory thresholds detection. This
      study has shown that VTs could be assessed during an incremental running test
      performed on a track using a simple beat-to-beat heart rate monitor, which is
      less expensive and complex than the classical respiratory measurement devices.

PMID- 17024638
TI  - Plasma protein carbonyl response to increasing exercise duration in aerobically
      trained men and women.
AB  - The purpose of this study was to determine the effect of aerobic exercise
      duration on plasma protein carbonyl concentrations, a marker of protein
      oxidation, in aerobically trained men and women. Eight men (age: 27 +/- 4 years,
      VO (2peak): 4.09 +/- 0.26 L x min (-1); mean +/- SD) and 7 women (age: 27 +/- 6
      years, VO (2peak): 2.33 +/- 0.24 L x min (-1)) exercised on an electrically
      braked cycle ergometer at 70 % VO (2peak) for 30, 60 or 120 minutes on three
      separate days. Plasma samples collected before and immediately, 30- and 60
      minutes post-exercise were analyzed for protein carbonyls. Mean oxygen uptake was
      greater for men in all conditions (2.75 +/- 0.03 L x min (-1); 38 +/- 0.43 ml x
      kg (-1) x min (-1)) compared to women (1.57 +/- 0.03 L x min (-1); 24.1 +/- 0.47
      ml x kg (-1) x min (-1)). Total work performed during the exercise sessions was
      also greater for men than for women during the 30 (368 +/- 11 versus 223 +/- 7
      kJ), 60 (697 +/- 17 versus 423 +/- 18 kJ), and 120-minute conditions (1173 +/- 44
      versus 726 +/- 28 kJ) (Mean +/- SEM). Although these comparisons were significant
      (p < 0.0001), sex differences in total work performed and mean VO (2) did not
      result in sex differences in protein carbonyls. However, a condition by time
      interaction was observed with greater post-exercise values following the 120
      minute condition compared to both the 30- and 60-minute conditions. Protein
      carbonyl concentration was greatest immediately post-exercise for both men and
      women and generally declined in a linear trend through one hour of recovery.
      These data suggest that protein carbonyl concentration is elevated by cycling
      exercise performed at 70 % VO (2peak), is greater following longer duration
      rides, begins to recover within one hour following exercise, and is not different
      between men and women.

PMID- 17024639
TI  - Effects of Hemopure on maximal oxygen uptake and endurance performance in healthy
      humans.
AB  - Haemoglobin-based oxygen carriers (HBOCs) such as Hemopure are touted as a
      tenable substitute for red blood cells and therefore potential doping agents,
      although the mechanisms of oxygen transport of HBOCs are incompletely understood.
      We investigated whether infusion of Hemopure increased maximal oxygen uptake (V.O
      2max) and endurance performance in healthy subjects. Twelve male subjects
      performed two 4-minute submaximal exercise bouts equivalent to 60 % and 75 % of
      V.O (2max) on a cycle ergometer, followed by a ramped incremental protocol to
      elicit V.O (2max). A crossover design tested the effect of infusing either 30 g
      (6 subjects) or 45 g (6 subjects) of Hemopure versus a placebo. Under our study
      conditions, Hemopure did not increase V.O (2max) nor endurance performance.
      However, the infusion of Hemopure caused a decrease in heart rate of
      approximately 10 bpm (p=0.009) and an average increase in mean ( approximately 7
      mmHg) and diastolic blood pressure ( approximately 8 mmHg) (p=0.046) at
      submaximal and maximal exercise intensities. Infusion of Hemopure did not bestow
      the same physiological advantages generally associated with infusion of red blood
      cells. It is conceivable that under exercise conditions, the hypertensive effects
      of Hemopure counter the performance-enhancing effect of improved blood oxygen
      carrying capacity.

PMID- 17024640
TI  - Loss of motor control and/or loss of consciousness during breath-hold
      competitions.
AB  - Since the first official world championships in breath-hold diving (1996), a
      sport has developed where the athletes compete in various disciplines of breath
      hold diving. One of the rules is that the diver should surface from a dive
      without showing any signs of hypoxia. Depending on the severity of hypoxia, a
      diver may suffer disqualifying signs such as loss of consciousness (LOC) or loss
      of motor control (LMC), the latter including signs such as confusion, affected
      postural control, spasms or speech problems. Data was collected from the results
      of the major international competitions following AIDA guidelines (Association
      International pour le Development de l'Apnee) in 1998, 2001-2004. The data was
      analyzed for frequency of LOC and LMC during constant weight diving and during
      static apnea. In constant weight diving, the diver swims down (and up) as deeply
      as possible along a vertically suspended rope (current record 105 m). In static
      apnea, the diver strives for maximum duration, floating motionless face down in a
      pool (current record 8.58 min). A total of 601 static apnea (SA) performances and
      596 constant weight dives were judged in the six competitions. On average, 10 %
      of SA, and 11 % of CW performances were disqualified due to signs of hypoxia. For
      the competitions in 2002-2004, a distinction was made in the rules between LOC
      and LMC; of a total number of 355 SA performances, 1.1 % resulted in LOC, while
      9.6 % resulted in LMC. For CW, the number was 344 with 6.1 % LOC and 6.1 % LMC.
      Despite the relatively high incidence of dramatic signs, it is noteworthy that
      there have been no reports of fatal accidents or permanent injuries from any of
      the above-mentioned competitions. This descriptive paper shows a relatively high
      incidence of disqualifications due to signs of hypoxia in breath-hold
      competitions 1998-2004.

PMID- 17024641
TI  - Effect of ankle joint stiffness during eccentric phase in rebound jumps on ankle
      joint torque at midpoint.
AB  - The purposes of this study were to investigate firstly, the ankle joint stiffness
      during the eccentric phase in rebound jumps, and secondly, the effect of ankle
      joint stiffness during the eccentric phase on ankle joint torque at midpoint.
      Nine active males executed rebound drop jumps from a height of 30 cm (RDJ30) and
      50 cm (RDJ50), and 5-repetition rebound jumps (5RJ). Force plate data, limb
      position and electromyogram (EMG) of the medial head of gastrocnemius (GAS),
      soleus (SOL), and tibialis anterior (TA) muscles were recorded simultaneously
      during all jumps. When compared with RDJ30 and RDJ50, 5RJ displayed significantly
      higher jumping height, ankle joint torque at midpoint, ankle joint stiffness
      during the eccentric phase, and integrated EMG (IEMG) of GAS and SOL.
      Furthermore, 5RJ displayed significantly lower contact time and IEMG of TA than
      RDJ30 and RDJ50 did. The ankle joint torque at midpoint showed a significant
      positive correlation with jumping height but a significant negative correlation
      with contact time in rebound jumps. There was a significant positive correlation
      between the ankle joint stiffness during the eccentric phase and ankle joint
      torque at midpoint in rebound jumps. These results suggested that for the rebound
      jumps to be effective, it may be important to enhance the ankle joint torque at
      midpoint by greater ankle joint stiffness during the eccentric phase. These
      results also suggested that compared to 5RJ, RDJ30 and RDJ50 may reduce ankle
      joint stiffness in order to protect the tendomuscular system from the stretch
      load. However, ankle joint stiffness is possibly increased in 5RJ because the
      restraint to defend the tendomuscular system is reduced by prediction or
      adaptation to the stretch load because it is a continuous jump.

PMID- 17024642
TI  - Do ankle foot orthoses modify postural control during bipedal quiet standing
      following a localized fatigue of the ankle muscles?
AB  - The purpose of the present experiment was to investigate the effects of wearing
      ankle foot orthoses (AFO) on postural control during bipedal quiet standing
      following a localized fatigue of the ankle muscles. To this aim, eight young
      healthy subjects were asked to stand upright as immobile as possible with and
      without AFO in two conditions of non-fatigue and fatigue of the ankle muscles.
      The center of foot pressure displacements (CoP) were recorded using a force
      platform. Larger CoP displacements in the fatigue than non-fatigue condition were
      observed without AFO along both the medio-lateral and antero-posterior axes.
      Interestingly, with AFO, these destabilizing effects were not observed along the
      medio-lateral axis. Altogether, the present findings suggested that the AFO
      allowed the subjects to limit the postural perturbation induced by a localized
      fatigue of the ankle muscles during bipedal quiet standing.

PMID- 17024643
TI  - Development and evaluation of a new bicycle instrument for measurements of pedal
      forces and power output in cycling.
AB  - Determination of pedal forces is a prerequisite to analyse cycling performance
      capability from a biomechanical point of view. Comparing existing pedal force
      measurement systems, there are methodological or practical limitations regarding
      the requirements of scientific sports performance research and enhancement.
      Therefore, the aim of this study was to develop and to validate a new bicycle
      instrument that enables pedal forces as well as power output measurements with a
      free choice of pedal system. The instrument (Powertec-System) is based on force
      transducer devices, using the Hall-Effect and being mounted between the crank and
      the pedal. Validation of the method was evaluated by determining the accuracy,
      the cross talk effect, the influence of lateral forces, the reproducibility and,
      finally, a possible drift under static conditions. Dynamic tests were conducted
      to validate the power output measurement in reference to the SRM-System. The mean
      error of the present system was -0.87 +/- 4.09 % and -1.86 +/- 6.61 % for,
      respectively, the tangential and radial direction. Cross talk, lateral force
      influence, reproducibility and drift mean values were < +/- 7 %, < or = 2.4 %, <
      0.8 % and 0.02 N x min (-1), respectively. In dynamic conditions, the power
      output measurement error could be kept below 2.35 %. In conclusion, this method
      offers the possibility for both valid pedal forces and power output measurements.
      Moreover, the instrument allows measurements with every pedal system. This method
      has an interesting potential for biomechanical analyses in cycling research and
      performance enhancement.

PMID- 17024644
TI  - Epidemiology and risk factors of sports injuries--multivariate analyses using
      German national data.
AB  - Representative data on the incidence of sports injuries and the risk groups
      involved is extremely rare. The data generated by the "First National Health
      Survey for the Federal Republic of Germany", conducted between October 1997 and
      March 1999, included information on the incidence of sports injuries requiring
      medical care and the associated sick leave, fitness indicators, and potential
      risk factors. The data was collected on the basis of a standardised cross
      sectional questionnaire. The net sample comprised 6687 subjects aged 18 to 79.
      3.1 % of adult Germans sustained a sports-related injury within the foregoing
      year. The annual incidence of injury among those actively engaging in sports is
      5.6 %. 62 % of all sports injuries result in sick leave. The period off work was
      longer than 30 days in only one out of five cases. Three out of four injured
      recreational athletes are male. The incidence declines significantly in the more
      senior population. These differences apply even if the specific sporting profile
      is factored in. Analysis of incidence rates on their own is misleading for some
      population groups. For instance, although individuals of normal weight and a good
      fitness display more than twice the average incidence of sports injuries, our
      study shows that these figures do not reflect the actual risk of injury, as
      bivariate calculation of incidence does not take account of the specific extent
      of sporting activity. When specific participation rates and the intensity of
      training are taken into account, no significant differences in the risk of injury
      are apparent. Our representative data also shows that future injury prevention
      strategies should focus on the highest risk group of young male recreational
      athletes.

PMID- 17024645
TI  - Effect of eating frequency on body composition in 9-11-year-old children.
AB  - The aim of this study was twofold: a) to examine the association between eating
      frequency and body composition in children, and b) to identify possible factors
      that may explain this relationship. Body composition (anthropometry) and dietary
      intake (3-day food records) were assessed in a cohort of 151 children. After
      excluding the underreporters (n = 20), data from 131 children (66 boys and 65
      girls) aged 9.9 +/- 0.1 yr with a BMI of 19.6 +/- 0.4 kg/m (2) (means +/- se)
      were used for further analysis. Children were categorized in tertiles based on
      the daily number of eating episodes. Physical activity was assessed in a subgroup
      of 48 volunteers with 4-day accelerometry (RT3, Stayhealthy Inc., Monrovia, CA,
      USA). The number of eating episodes was inversely associated (p < 0.05) with the
      sum of skinfolds (r = - 0.17) and % body fat (r = - 0.18) after controlling for
      age and sex. Frequent eaters presented lower total (p < 0.05) and central
      adiposity (p < 0.01) compared with the infrequent ones. This was despite the fact
      that energy intake was higher for the frequent eaters (2077.0 +/- 64.3 vs. 1813.0
      +/- 37.8 kcals/day for the frequent and the infrequent eaters, respectively, p <
      0.05). Actually, frequent eaters devoted more time to physical activity than
      infrequent ones (624.7 +/- 13.5 vs. 559.2 +/- 23.1 min/day, p < 0.05). In
      conclusion, high eating frequency was associated with more favorable body
      composition in this cohort of school children. Increased energy expenditure due
      to physical activity may, at least in part, explain the favorable body
      composition of children who eat frequently.

PMID- 17024646
TI  - Carbohydrate supplementation and endurance performance of moderate altitude
      residents at 4300 m.
AB  - Recent work from our laboratory demonstrated that carbohydrate supplementation
      (CHOS) during exercise improved prolonged time-trial (TT) performance of sea
      level residents (SLR) living at 4300 m while they were in daily negative energy
      balance (- 1250 kcal x day (-1); [ ]). The purposes of the current study were to
      determine during initial exposure to 4300 m:1) whether CHOS also improves TT
      performance of moderate altitude residents (MAR) who are in energy balance and 2)
      if acclimatization to moderate elevations benefits TT performance. Fifteen Air
      Force Academy (AFA) active duty members (age: 30 +/- 1 yrs; mean +/- SE), who had
      been living at approximately 2000 m for 21 +/- 3 months performed a maximal
      effort 720-kJ cycle TT at the AFA and at Pikes Peak (PP), CO, (4300 m) on days 1
      (PP1) and 3 (PP3). Daily energy intake and expenditure were maintained similarly
      at the AFA and PP. At the start of the TTs at PP, and then every 15 min
      thereafter, 9 subjects drank a 10 % CHO solution (0.175 g x kg (-1) body weight)
      and 6 subjects drank a placebo (PLA) solution. All subjects were allowed to
      freely adjust the power output of the cycle ergometer and drank water AD LIBITUM.
      Performance time did not differ between groups on PP1 (CHOS vs. PLA; 101 +/- 8
      vs. 116 +/- 10 min) or PP3 (95 +/- 8 vs. 107 +/- 12 min). For both groups, cycle
      times on PP1 and PP3 were longer compared to the AFA (p<0.01) and were improved
      from PP1 to PP3 (p<0.05). Exercise intensity (i.e., % peak oxygen uptake) was
      maintained similarly at approximately 62 % during the TTs at the AFA and PP.
      Blood glucose was 1.5 to 2.0 mmol x L (-1) higher for CHOS vs. PLA (p<0.01). It
      was concluded that CHOS provided no TT performance benefit for MAR at 4300 m when
      energy balance was maintained. However, the decrements in TT performance and
      exercise intensity were attenuated at 4300 m in MAR compared to those of SLR as a
      result of acclimatization attained while living for nearly 2 years at
      approximately 2000 m.

PMID- 17024647
TI  - Effects of a 28-day "living high--training low" on T-lymphocyte subsets in soccer
      players.
AB  - The purpose of this study was to investigate the changes in T-lymphocyte subsets
      in soccer players during "living high--training low" (LHTL) for 28 days in
      comparison to equally trained control players. Sixteen male soccer players were
      randomly assigned into two groups. The LHTL group lived in normobaric hypoxic
      rooms, simulating an altitude of 3000 m for 10 hours per night for 28 days. The
      control group lived at sea level. Both LHTL and control groups trained together
      at sea level and completed the same training schedules. The blood samples were
      collected prior to the trial (baseline) and at 1, 14, 21 and 28 days of the
      trial, respectively. Lymphocyte subsets were quantitated using the recommended
      flow cytometry method. The results showed that the relative changes from the
      baseline in the CD4 (+)/CD8 (+) ratio, in both LHTL and control groups, followed
      a similar downward trend during the trial. However, the trend was more pronounced
      in the LHTL group. In the LHTL group, significant differences were seen at both
      14 and 28 days compared to the baseline. In addition, a significant difference
      was also observed between the groups at 14 days. During LHTL, hypoxia may augment
      the effect which training may have on T-lymphocyte subsets after 14 days, even
      when training was not performed under hypoxic condition. The long term effect of
      LHTL was unknown at this time and needs further investigation.

PMID- 17024648
TI  - RAS and MTHFR gene polymorphisms in a healthy exercise-trained population:
      association with the MTHFR (TT) genotype and a lower hemoglobin level.
AB  - The aim of this study was to determine the frequencies of ACE (I/D), AGT (M235T),
      AT1R (A1166C) and MTHFR (C677T) polymorphisms in a well-defined (in regards to
      health and nutritional status and lifestyle) population of young, healthy,
      exercise-trained subjects (no. 100) from the Campania region of Southern Italy.
      We also investigated whether there was any correlation between these
      polymorphisms and biochemical, hematological and hemostatic parameters in this
      "low-risk" population. Gene polymorphisms were analyzed with the polymerase chain
      reaction and restriction enzyme analysis. Allele frequencies of the genotypes
      examined were in Hardy-Weinberg equilibrium and agree with those reported in the
      Italian population. No associations were found between ACE, AGT, AT1R gene
      polymorphisms and anthropometric, clinical and laboratory parameters. However,
      the MTHFR (C677T) polymorphism was significantly associated with lower hemoglobin
      plasma levels in TT vs. CC + CT females (p < 0.016). This report is the first to
      describe the frequencies of RAS and MTHFR gene polymorphisms in young, exercise
      trained volunteers from Campania and to identify an association between the MTHFR
      gene polymorphisms and lower hemoglobin plasma levels in young healthy females.

PMID- 17024649
TI  - High-altitude exposure reduces inspiratory muscle strength.
AB  - It was the aim of the study to assess the maximal pressure generated by the
      inspiratory muscles (MIP) during exposure to different levels of altitude (i.e.,
      hypobaric hypoxia). Eight lowlanders (2 females and 6 males), aged 27 - 46 years,
      participated in the study. After being evaluated at sea level, the subjects spent
      seven days at altitudes of more than 3000 metres. On the first day, they rode in
      a cable car from 1200 to 3200 metres and performed the first test after 45 - 60
      minutes rest; they then walked for two hours to a mountain refuge at 3600 metres,
      where they spent three nights (days 2 - 3); on day 4, they walked for four hours
      over a glacier to reach Capanna Regina Margherita (4559 m), where they spent days
      5 - 7. MIP, flow-volume curve and SpO (2) % were measured at each altitude, and
      acute mountain sickness (Lake Louise score) was recorded. Increasing altitude led
      to a significant decrease in resting SpO (2) % (from 98 % to 80 %) and MIP (from
      134 to 111 cmH (2)O) (baseline to day 4: p < 0.05); there was an improvement in
      SpO (2) % and a slight increase in MIP during the subsequent days at the same
      altitude. Expiratory (but not inspiratory) flows increased, and forced vital
      capacity and FEF (75) decreased at higher altitudes. We conclude that exposure to
      high altitude hypoxia reduces the strength of the respiratory muscles, as
      demonstrated by the reduction in MIP and the lack of an increase in peak
      inspiratory flows. This reduction is more marked during the first days of
      exposure to the same altitude, and tends to recover during the acclimatisation
      process.

PMID- 17024650
TI  - Relationship between dyspnea increase and ventilatory gas exchange thresholds
      during exercise in children with surgically corrected heart impairment.
AB  - To study the relationship between the onset of an increase in dyspnea and
      ventilatory threshold (VT) in children with congenital heart impairment, sixteen
      young subjects underwent a cardiopulmonary exercise test with dyspnea perception
      and ventilatory gas exchange assessments. Dyspnea score was measured from a
      visual analogical scale at rest and during each step of an incremental exercise
      test. Dyspnea score was plotted against oxygen uptake and the onset of an
      increase in dyspnea (DT) was determined when a brutal disruption occurs on the
      dyspnea score-oxygen uptake curve. VT was defined from gas exchange according to
      Beaver's method. The first breakdown point in the oxygen uptake-carbon dioxide
      production relationship locates VT. Oxygen uptake (V(.-)O (2)), pulmonary
      ventilation (V(.-)E), heart rate (HR), oxygen pulse (O (2) pulse = V(.-)O
      (2)/HR), carbon dioxide production (V(.-)CO (2)) and power output (P) were
      measured both at VT and DT effort level. Results pointed out that there was no
      significant difference between the cardiorespiratory variables measured
      respectively at VT and DT: V(.-)O (2) (VTV(.-)O (2) = 16.71 +/- 2.65 vs. DTV(.-)O
      (2) = 18.34 +/- 5.74 ml x kg (-1) x min (-1)), V(.-)E (VTV(.-)E = 24.33 +/- 6.86
      vs. DTV(.-)E = 26.82 +/- 9.59 l x min (-1)), (VTV(.-)CO (2) = 789.31 +/- 165.17
      vs. DTV(.-)CO (2) = 924.02 +/- 342.28 ml x min (-1)), HR (VTHR = 116 +/- 10 vs.
      DTHR = 123 +/- 20 beat x min (-1)), O (2) pulse (VT O (2) pulse = 7.83 +/- 2.00
      vs. DT O (2) pulse = 8.01 +/- 2.13 ml x kg (-1) x beat (-1)), and P (VTP = 43 +/-
      16 vs. DTP = 52 +/- 27 W). Moreover, the cardiorespiratory variables measured at
      DT and VT were closely related: V(.-)O (2) (r = 0.64, p < 0.01), V(.-)E (r =
      0.51, p < 0.01), HR (r = 0.75, p < 0.02), O (2) pulse (r = 0.90, p < 0.001), and
      P (r = 0.80, p < 0.01). In addition, according to Bland and Altman's procedure,
      the onset of dyspnea increase and ventilatory threshold were shown in close
      agreement for the cardiorespiratory variables measured at these effort levels.
      The standard errors of the estimates were low. It was concluded that dyspnea and
      ventilatory gas exchange thresholds occur concomitantly and were strongly
      correlated in children with congenital heart impairment. The use of the onset of
      dyspnea increase for aerobic capacity assessment may be a good alternative to
      ventilatory gas exchange threshold measurement.

PMID- 17024651
TI  - Doping, drugs and drug abuse among adolescents in the State of Thuringia
      (Germany): prevalence, knowledge and attitudes.
AB  - Goal-directed measures to prevent doping and drug abuse in sports requires
      empirical data. In this connection, a cross-sectional analysis was carried out in
      2004. The purpose of the study, on the one hand, was to register reliable data of
      the current situation in Thuringia, and, on the other hand it was to give
      information on possible interventional steps with scientific support. Within
      three months, 2319 adolescents from 16 Thuringian schools (5 regular schools, 4
      secondary schools, 3 sport schools and 4 vocational schools) were surveyed. Three
      hundred and forty-six (15.1 %) students out of 2287 students (26 students without
      a statement) indicated use of prohibited substances from the WADA list in the
      previous year: 16 (0.7 %) anabolic-androgenic steroids (AAS), 10 (0.4 %) growth
      hormones, 56 (2.4 %) stimulants, 305 (13.2 %) cannabis, 2 (0.1 %) diuretics, 52
      (2.2 %) cocaine/heroin and 6 (0.3 %) erythropoeitin. Moreover, nonathletes (N =
      490) reported a substance use that was approximately 5.0 % higher than that of
      recreational athletes (N = 1254) and nearly three times higher than that of
      competitive athletes (497). All three groups (nonathletes, recreational athletes
      and competitive athletes) performed poorly on a knowledge test regarding doping
      in general with an average below 60 % in each case. Another main aspect of the
      study was to determine factors influencing substance use in sports. Besides the
      doping specific knowledge (beta = 0.06, p < 0.05), age contributed (beta = 0.09,
      p < 0.05), as well as anti-doping attitude (beta = -0.34, p < 0.05), to the
      resulting variance. Gender, however, played no role. The findings of the study
      point towards the need for improvement of specific knowledge of doping among
      students and that their attitude towards doping must be altered. The goal in this
      case is to test the effectiveness of appropriate scientific intervention.

PMID- 17024652
TI  - Eating attitudes, body esteem, perfectionism and anxiety of judo athletes and
      nonathletes.
AB  - The aim of the study was to examine the prevalence and relationships between
      disordered eating, menstrual irregularity, musculoskeletal injuries and
      psychological characteristics in 24 judo athletes (12 females and 12 males) and
      31 controls (14 females and 17 males). All these parameters were assessed by a
      health/medical, dieting and menstrual history questionnaire, the Eating Attitudes
      Test (EAT-26), the Multidimensional perfectionism scale, the Rosenberg Self
      esteem, the Body esteem scale, and the Profile of Mood States. Body mass index
      (BMI) was also computed. Twenty-five percent of female athletes would be "at
      risk" of EDs (EAT-26 > 20) and 0 % in the other sample groups. Bone injuries
      sustained over the judo athlete career were reported by 25 % of females and 33.3
      % of males, while 35.7 % of the female controls reported bone injuries. The total
      frequency of menstrual dysfunction among judo athletes was 58.3 %, while 7.1 % of
      female controls reported oligoamenorrhea. Regression analyses showed that BE
      Weight Satisfaction and BMI contributed to 54.6 % and 17 % of the variance,
      respectively, in the prediction of log-transformed Global EAT scores among female
      judo athletes. These data indicate that while the prevalence of clinical eating
      disorders is low in judo athletes, many are "at risk" for an eating disorder,
      which places them at an increased risk for menstrual irregularity and bone
      injuries. This study also highlights the relevance of body esteem to eating
      disorder symptoms.

PMID- 17024653
TI  - Fast track to a phosphoprotein sketch - MALDI-TOF characterization of TLC-based
      tryptic phosphopeptide maps at femtomolar detection sensitivity.
AB  - Tryptic phosphopeptide mapping by TLC on microcrystalline cellulose has been a
      convenient method to get a fast and highly reproducible overview of the number of
      phosphopeptides present in any given (32)P-labeled phosphoprotein. This method
      also provides an immediate presentation of the relative phosphorylation
      stoichiometry between individual phosphopeptides. However, so far, traditional
      tryptic phosphopeptide maps have not been useful for phosphoproteomics
      applications, as the S/N has been very poor, due to the large number of quenching
      substances and contaminants present on cellulose plates. In this study, we
      present a rapid and easy method for phosphopeptides identification from 2-D
      phosphopeptide maps (2-D-PPMs). We obtain improved sensitivity (femtomole levels)
      upon MALDI-TOF MS analysis of phosphopeptides extracted from 2-D-PPMs. Using this
      approach we could confidently characterize the major phosphorylation sites of in
      vivo and in vitro (32)P-labeled proteins.

PMID- 17024654
TI  - Stepwise carcinogenesis of hepatocellular carcinoma in the cirrhotic liver:
      demonstration on serial MR imaging.
AB  - PURPOSE: To demonstrate imaging findings of stepwise carcinogenesis of
      hepatocellular carcinoma (HCC) in cirrhosis at serial state-of-the-art MR imaging
      exams. MATERIALS AND METHODS: In a retrospective search of the hospital archives,
      three patients were identified in which developing HCC was observed in serial MR
      examinations, with histopathology or alpha-fetoprotein (AFP) correlation. Image
      findings were assessed for signal intensity of the lesions at multiple sequences,
      including dynamic gadolinium-enhanced imaging. RESULTS: Initial findings in
      patient A showed a small nodule with fatty infiltration that developed in HCC in
      follow-up MRI, comprised of low-grade dysplastic nodule (DN; DN I), high-grade DN
      (DN II), and eventually classic HCC. In patient B, increased signal intensity on
      T2-weighted images in a single DN among numerous regenerative nodules was the
      only initial sign. Follow up MRI showed further increase in signal intensity and
      increased neovascularity, which suggested focal HCC in a DN II. Patient C
      demonstrated gradually increasing neovascularity as only initial sign, with
      development of classic HCC over time. CONCLUSION: MR imaging provides insight in
      various pathways of stepwise carcinogenesis of developing HCC in cirrhosis. This
      may further explain the genetic heterogeneity, and may facilitate early detection
      and better selection of patients for follow-up.

PMID- 17024655
TI  - Identification of fibers at risk for degeneration by diffusion tractography in
      patients at high risk for MS after a clinically isolated syndrome.
AB  - PURPOSE: Focal inflammatory/demyelinating lesions are thought to be the source of
      Wallerian degeneration or other injury to local, transiting fiber tracts in the
      brain or spinal cord in multiple sclerosis (MS). A methodology is established to
      isolate connections between focal demyelinating lesions and intersecting fibers
      to permit explicit analyses of the pathology of secondary fiber injury distant
      from the focal lesion. MATERIALS AND METHODS: A strategy is described and
      feasibility demonstrated in three patients with a clinically isolated syndrome
      and positive MRI (at high risk for MS). The strategy utilizes streamtube
      diffusion tractography to identify neuronal fibers that intersect a focal lesion
      and pass through a region of interest, in this case the corpus callosum, where
      distal (to focal lesion) interrogation can be accomplished. RESULTS: A sizeable
      fraction of the normal appearing white matter (NAWM) in the early stages of
      disease can be defined in the corpus callosum, which is distinctive in that this
      tissue connects to distant demyelinating lesions. CONCLUSION: The new class of
      tissue called fibers-at-risk for degeneration (FAR) can be identified and
      interrogated by a variety of quantitative MRI methodologies to better understand
      neuronal degeneration in MS.

PMID- 17024656
TI  - Brain hydrodynamics study by phase-contrast magnetic resonance imaging and
      transcranial color doppler.
AB  - PURPOSE: To evaluate the contributions of phase-contrast magnetic resonance
      (PCMR) and transcranial color Doppler (TCCD) imaging in the investigation of
      cerebral hydrodynamics. MATERIALS AND METHODS: A total of 13 healthy subjects
      were studied. Blood velocity measurements were performed with TCCD and gated PCMR
      imaging in major intracranial and extracranial arteries stages. Peak systolic
      velocity and end-diastolic velocity were extracted to establish correlations
      between TCCD and PCMR imaging. Cerebral blood flow (CBF) and intracranial volume
      change (IVC) during the cardiac cycle were calculated, taking into account
      cerebrospinal fluid (CSF) oscillations. RESULTS: Despite an underestimation of
      velocities with PCMR imaging, significant correlations were observed for velocity
      measurements between the two modalities in extracranial vessels, but were poorly
      correlated in intracranial vessels. PCMR data processing gave a mean CBF of 690+/
      90 mL/minute. CONCLUSION: PCMR imaging provides complementary information to TCCD
      to assess various intracranial parameters such as instantaneous velocities, blood
      and CSF flow distributions, volume variation, or pressure regulation mechanisms
      during cardiac cycles.

PMID- 17024657
TI  - Analysis of connexin expression during mouse Schwann cell development identifies
      connexin29 as a novel marker for the transition of neural crest to precursor
      cells.
AB  - Connexins are transmembrane proteins forming gap junction channels for direct
      intercellular and, for example in myelinating glia cells, intracellular
      communication. In mature myelin-forming Schwann cells, expression of multiple
      connexins, i.e. connexin (Cx) 43, Cx29, Cx32, and Cx46 (after nerve injury) has
      been detected. However, little is known about connexin protein expression during
      Schwann cell development. Here we use histochemical methods on wildtype and
      Cx29lacZ transgenic mice to investigate the developmental expression of connexins
      in the Schwann cell lineage. Our data demonstrate that in the mouse Cx43, Cx29,
      and Cx32 protein expression is activated in a developmental sequence that is
      clearly correlated with major developmental steps in the lineage. Only Cx43 was
      expressed from neural crest cells onwards. Cx29 protein expression was absent
      from neural crest cells but appeared as neural crest cells generated precursors
      (embryonic day 12) both in vivo and in vitro. This identifies Cx29 as a novel
      marker for cells of the defined Schwann cell lineage. The only exception to this
      were dorsal roots, where the expression of Cx29 was delayed four days relative to
      ventral roots and spinal nerves. Expression of Cx32 commenced postnatally,
      coinciding with the onset of myelination. Thus, the coordinated expression of
      connexin proteins in cells of the embryonic and postnatal Schwann cell lineage
      might point to a potential role in peripheral nerve development and maturation.

PMID- 17024658
TI  - Amplification strategies in MR imaging: activation and accumulation of sensing
      contrast agents (SCAs).
AB  - We review new strategies for the development of Gd3+-based T1-relaxation agents
      and paramagnetic chemical exchange saturation transfer (PARACEST) "sensing"
      contrast agents (SCAs) designed specifically to detect small molecules or
      enzymatic activity in living systems. The first class of agents exhibits
      molecular "sensing" properties as a result of water coordination sphere effects,
      cleavage, or synthesis of reactive precursor compounds that recombine with
      macromolecules with the resultant formation of immobilized or rotationally
      constrained paramagnetic cations. This effect results in changes of water proton
      relaxation times. The second class (PARACEST) comprises a family of lanthanide
      based paramagnetic compounds suitable for CEST imaging. The need for both types
      of MR agents is justified by efforts to utilize magnetic resonance imaging (MRI)
      to visualize fine structures in living tissue, and to increase the molecular
      specificity of MRI.

PMID- 17024659
TI  - Astrocytic localization of kynurenine aminotransferase II in the rat brain
      visualized by immunocytochemistry.
AB  - Kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan
      degradation, is a neuroinhibitory agent present in the mammalian brain.
      Endogenous KYNA preferentially affects the alpha7 nicotinic acetylcholine
      (alpha7nACh) receptor and, possibly, the glycine co-agonist (glycineB) site of
      the NMDA receptor. Functionally relevant fluctuations in brain KYNA occur under
      both physiological and pathological conditions, affecting cholinergic and
      glutamatergic neurotransmission. Kynurenine aminotransferase II (KAT II), the
      major biosynthetic enzyme of KYNA in the rat brain, catalyzes the irreversible
      formation of KYNA from its immediate bioprecursor, kynurenine. We now purified
      rat kidney KAT II to homogeneity, generated a polyclonal rabbit anti-rat KAT II
      antibody, and purified the antibody using routine biochemical methods. The
      antibody selectively recognized KAT II by Western blot analysis and in
      immunotitration experiments. Used for immunocytochemistry, the antibody revealed
      discrete, specific staining of KAT II-positive astrocyte-like cells throughout
      the adult rat brain. The presence of KAT II in astrocytes was confirmed by double
      fluorescence immunostaining with an antibody against the astrocyte-specific
      marker glial fibrillary acidic protein (GFAP). No specific labeling was detected
      in neurons or microglia. However, KAT II-positive astrocytes were intimately
      associated with select neuron populations, supporting a neuromodulatory role of
      KYNA. Intense staining was frequently seen around brain capillaries, with
      astrocytic end feet contacting the capillary wall. This may explain the rapid
      access of blood-derived kynurenine to KAT II-containing astrocytes. The new anti
      KAT II antibody should be useful in the further elucidation of the presumed role
      of KYNA in brain physiology and pathology.

PMID- 17024660
TI  - Repeatability of a reference region model for analysis of murine DCE-MRI data at
      7T.
AB  - PURPOSE: To test the repeatability of a reference region (RR) model for the
      analysis of dynamic contrast-enhanced MRI (DCE-MRI) in a mouse model of cancer at
      high field. MATERIALS AND METHODS: Seven mice were injected with 10(6) 4T1
      mammary carcinoma cells and imaged eight to 10 days later on a Varian 7.0T
      scanner. Two DCE-MRI studies were performed for each mouse (separated by 2.5
      hours). The RR model was used to analyze the data, and returned estimates on the
      perfusion-permeability index (Ktrans) for the RR and the tissue of interest
      (TOI), as well as the extravascular extracellular volume fraction (ve) for the
      TOI. RESULTS: When the first injection was compared with the second injection,
      all parameters tested were highly correlated (r2=0.90, 0.62, 0.82 for the RR
      Ktrans, TOI Ktrans, and TOI ve, respectively, with P<0.001 for all). To observe a
      statistically significant change (at the 5% level) in a treatment study with
      seven animals in each group, log10 changes of 0.084 and 0.077 in the tumor Ktrans
      and ve, respectively, are required. CONCLUSION: If a reliable arterial input
      function (AIF) is unavailable, the RR model is a reasonable alternative to
      measuring MRI contrast-agent (CA) kinetics in mouse models of cancer at high
      field.

PMID- 17024661
TI  - The utility of zebrafish for studies of the comparative biology of motor systems.
AB  - Although zebrafish are best known as a model for studies of development, there is
      now a growing role for the model in studies of the functional organization of the
      nervous system, including studies of a variety of sensory systems, central
      processing, and motor output. The zebrafish has much to offer for such work
      because of the unique combination of genetics, optical methods, and physiology it
      allows. Here I illustrate, using three examples, the broad range of avenues along
      which zebrafish can inform us about motor systems. The examples include efforts
      to understand the functional organization and evolution of spinal interneurons,
      the role of mutants in informing us about motor dysfunction and human disease,
      and the ability to use the special features of zebrafish to explore strategies to
      restore function after injury. The most important aspects of these studies are
      evident only when they are placed in a comparative context, so they serve to
      highlight the power of zebrafish in studies of the comparative biology of motor
      control.

PMID- 17024662
TI  - Preoperative evaluation of the hepatic vascular anatomy in living liver donors:
      comparison of CT angiography and MR angiography.
AB  - PURPOSE: To compare the diagnostic performance of CT angiography (CTA) and MR
      angiography (MRA) for preoperative hepatic vascular evaluation in living liver
      donors. MATERIALS AND METHODS: Twenty-eight living donor candidates underwent
      preoperative CTA and MRA. Two blinded radiologists evaluated the anatomic types
      of the hepatic artery (HA) and portal vein (PV), and the number of aberrant
      hepatic veins (HVs) on both CTA and MRA, independently. Four grades of confidence
      levels were used to indicate the clarity of depiction of the HA and PV. Surgical
      findings were used as a standard of reference. RESULTS: For determining the
      anatomic types of the HA and PV, and the number of aberrant HVs, CTA and MRA did
      not significantly differ in terms of accuracy ([89%, 96%, and 68% on CTA] vs.
      [86%, 93%, and 68% on MRA] for reader 1, P>0.05; and [93%, 100%, and 86% on CTA]
      vs. [89%, 93%, and 79% on MRA] for reader 2, P>0.05). Confidence for the
      depiction of major branches of HA and PV did not differ between CTA and MRA,
      except for a better depiction of the left HA (LHA) on CTA (P<0.05) CONCLUSION: In
      living donor candidates, both CTA and MRA can provide a complete evaluation of
      the hepatic vascular anatomy.

PMID- 17024664
TI  - Genotype-phenotype correlations in von Hippel-Lindau disease.
AB  - von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer
      syndrome resulting from mutations in the VHL tumor suppressor gene. VHL disease
      displays marked variation in expression and the presence of pheochromocytoma has
      been linked to missense VHL mutations. We analyzed genotype-phenotype
      correlations in 573 individuals with VHL disease. Routine clinical and
      radiological surveillance of VHL patients and at-risk relatives was associated
      with increased detection of retinal angiomatosis (73 vs. 59% of cases) and a
      reduction in age at diagnosis of renal cell carcinoma (RCC) (44.0+/-10.9 vs.
      39.7+/-10.3 years). We confirmed the association of pheochromocytoma with
      missense mutations described previously, but stratifying missense mutations into
      those that resulted in substitution of a surface amino acid and those that
      disrupted structural integrity demonstrated that surface amino acid substitutions
      conferred a higher pheochromocytoma risk. Age at first manifestation of VHL
      disease was significantly earlier (P=0.001), and age-related risks of retinal
      angiomas and RCC were higher (P=0.022 and P=0.0008, respectively) in individuals
      with a nonsense or frameshift mutation than in those with deletions or missense
      mutations that disrupted the structural integrity of the VHL gene product (pVHL).
      These results extend genotype-phenotype-protein structure correlations in VHL
      disease and provide a baseline for future chemoprevention studies in VHL disease.

PMID- 17024663
TI  - Correction of eddy-current distortions in diffusion tensor images using the known
      directions and strengths of diffusion gradients.
AB  - PURPOSE: To correct eddy-current artifacts in diffusion tensor (DT) images
      without the need to obtain auxiliary scans for the sole purpose of correction.
      MATERIALS AND METHODS: DT images are susceptible to distortions caused by eddy
      currents induced by large diffusion gradients. We propose a new postacquisition
      correction algorithm that does not require any auxiliary reference scans. It also
      avoids the problematic procedure of cross-correlating images with significantly
      different contrasts. A linear model is used to describe the dependence of
      distortion parameters (translation, scaling, and shear) on the diffusion
      gradients. The model is solved numerically to provide an individual correction
      for every diffusion-weighted (DW) image. RESULTS: The assumptions of the linear
      model were successfully verified in a series of experiments on a silicon oil
      phantom. The correction obtained for this phantom was compared with correction
      obtained by a previously published method. The algorithm was then shown to
      markedly reduce eddy-current distortions in DT images from human subjects.
      CONCLUSION: The proposed algorithm can accurately correct eddy-current artifacts
      in DT images. Its principal advantages are that only images with comparable
      signals and contrasts are cross-correlated, and no additional scans are required.

PMID- 17024665
TI  - Respiratory-triggered MRCP applying parallel acquisition techniques.
AB  - PURPOSE: To evaluate the influence of parallel imaging on the image quality of
      respiratory triggered magnetic resonance cholangiopancreatography (MRCP).
      MATERIALS AND METHODS: A total of 30 consecutive patients underwent MRCP applying
      a respiratory triggered T2-weighted (T2w) turbo spin-echo (TSE) sequence without
      and with parallel imaging (acceleration factor of 2). Acquisition times of both
      sequences were recorded. Quantitative evaluation included measurement of a
      contour sharpness index of two segments of the pancreaticobiliary tree as well as
      calculation of the relative contrast between ductal structures and organ
      parenchyma at four different segments. The qualitative evaluation was performed
      by two independent radiologists who graded overall image quality, depiction of
      eight segments of the pancreaticobiliary tree, and the frequency of artifacts.
      RESULTS: The application of parallel imaging significantly (P<0.05) reduced the
      acquisition time of the respiratory triggered MRCP sequence by 37.7% (six minutes
      and two seconds+/-one minute and 26 seconds vs. three minutes and 46 seconds+/-58
      seconds). The quantitative and qualitative evaluation revealed no statistically
      significant differences between the two sequences (P>0.05). The frequency of
      artifacts was at the same level for both sequences as well. CONCLUSION: The
      application of parallel imaging for respiratory triggered MRCP significantly
      reduces the acquisition time without relevant influence on image quality.

PMID- 17024666
TI  - Understanding the recent evolution of the human genome: insights from human
      chimpanzee genome comparisons.
AB  - The sequencing of the chimpanzee genome and the comparison with its human
      counterpart have begun to reveal the spectrum of genetic changes that has
      accompanied human evolution. In addition to gross karyotypic rearrangements such
      as the fusion that formed human chromosome 2 and the human-specific pericentric
      inversions of chromosomes 1 and 18, there is considerable submicroscopic
      structural variation involving deletions, duplications, and inversions. Lineage
      specific segmental duplications, detected by array comparative genomic
      hybridization and direct sequence comparison, have made a very significant
      contribution to this structural divergence, which is at least three-fold greater
      than that due to nucleotide substitutions. Since structural genomic changes may
      have given rise to irreversible functional differences between the diverging
      species, their detailed analysis could help to identify the biological processes
      that have accompanied speciation. To this end, interspecies comparisons have
      revealed numerous human-specific gains and losses of genes as well as changes in
      gene expression. The very considerable structural diversity (polymorphism)
      evident within both lineages has, however, hampered the analysis of the
      structural divergence between the human and chimpanzee genomes. The concomitant
      evaluation of genetic divergence and diversity at the nucleotide level has
      nevertheless served to identify many genes that have evolved under positive
      selection and may thus have been involved in the development of human lineage
      specific traits. Genes that display signs of weak negative selection have also
      been identified and could represent candidate loci for complex genomic disorders.
      Here, we review recent progress in comparing the human and chimpanzee genomes and
      discuss how the differences detected have improved our understanding of the
      evolution of the human genome.

PMID- 17024667
TI  - An apparent unidirectional influx constant for manganese as a measure of
      myocardial calcium channel activity.
AB  - PURPOSE: To develop an in vivo MR method for evaluation of myocardial calcium
      channel activity through quantification of apparent unidirectional manganese
      influx constants following manganese dipyridoxyl-diphosphate (MnDPDP) infusions.
      MATERIALS AND METHODS: A total of 10 healthy volunteers were divided in two
      groups, and received 5 micromol of MnDPDP per kg of body weight intravenously in
      a 1.5 Tesla scanner over five or 30 minutes, respectively. A fast inversion
      recovery gradient echo sequence was used to estimate pre- and postcontrast R1
      values and to measure signal changes following infusions. By assuming equal
      longitudinal relaxivity (r1) of the contrast in all tissue compartments, signal
      changes in blood and myocardial tissue yielded temporal input and tissue contrast
      concentrations respectively. Through a two-tissue compartment model, apparent
      unidirectional influx constants (Ki) for myocardial manganese accumulation were
      estimated. RESULTS: Consistent values for Ki in left ventricular wall were found,
      with a mean value of 5.96 mL/100 g/minute (SD=0.49; N=10). No statistical
      significant differences in Ki were found between the two infusion groups.
      CONCLUSION: Since unidirectional manganese accumulation depends upon intact
      myocyte membranes with functioning calcium channels, the use of unidirectional
      manganese influx rates may be a valuable research tool for in vivo studies of
      myocyte functioning in myocardial disease.

PMID- 17024668
TI  - Tolerance for uncertainty and perceived risk among women receiving uninformative
      BRCA1/2 test results.
AB  - Women who receive uninformative BRCA1/2 genetic test results face ongoing
      uncertainty about their future cancer risks. This article prospectively examined
      the influence of intolerance for uncertainty and perceived breast cancer risk on
      psychological distress following the receipt of uninformative BRCA1/2 test
      results. Sixty-four women who received uninformative BRCA1/2 mutation test
      results completed measures of Intolerance for Uncertainty, perceived breast
      cancer risk, and measures of cancer-related, genetic testing, and general
      distress. Cancer-related (DeltaR(2) = 0.18, P < or = 0.001), general (DeltaR(2) =
      0.04, P < or = 0.05), and genetic testing distress (DeltaR(2) = 0.12, P < or =
      0.01) were associated with intolerance for uncertainty at 1 month post
      disclosure. The interaction of intolerance for uncertainty and breast cancer
      perceived risk predicted cancer-related (DeltaR(2) = 0.10, P < or = 0.001) and
      genetic testing distress (DeltaR(2) = 0.09, P < or = 0.01) at 6 months post
      disclosure. Distress was highest among patients with highest perceived risk and
      intolerance for uncertainty, suggesting that those who have difficulty coping
      with their ambiguous risk are at risk for long-term distress. The clinical and
      research implications of these results are discussed.

PMID- 17024669
TI  - Lost in transition: challenges in the expanding field of adult genetics.
AB  - It is increasingly clear that medical genetics has broad relevance in adult
      clinical medicine. More adult patients with genetic conditions are being
      recognized, genetic testing for adult-onset genetic conditions is expanding, and
      children with genetic conditions are now more likely to survive to adulthood.
      While the number of patients who could benefit from medical genetic services
      increases, adult care providers are less well educated about clinical genetics
      and are not sufficiently prepared to meet the growing needs of this population.
      Genetics professionals may also be ill-suited for this challenge, since
      geneticists and genetic counselors have traditionally had greater experience in
      pediatric and prenatal settings. Communication between primary care physicians
      who treat adults and the genetics community is currently suboptimal and the
      identification and subsequent referral of adult patients for genetic services
      need improvement. Finally, published guidelines that address how to deliver
      genetic services to adult patients are unavailable for many genetic conditions.
      In this article we address the challenges of transitioning genetics services from
      traditional, and largely pediatric-based models to paradigms that can best
      address the needs of adult patients with genetic conditions. Potential solutions
      and the practicality of implementation of a team-based approach to adult genetic
      medicine, including the application of genetic counseling, are also discussed.

PMID- 17024670
TI  - Sonographic diagnosis of appendicitis within a right inguinal hernia (Amyand's
      hernia).
AB  - We report a case of acute appendicitis occurring within a right inguinal hernia
      also known as Amyand's hernia-in a 59-year-old man. The correct diagnosis was
      made via preoperative inguinal sonography and was confirmed via CT, allowing
      prompt appropriate surgical management.

PMID- 17024672
TI  - Sonographic diagnosis of a saccular aneurysm of the internal jugular vein.
AB  - Aneurysm of the internal jugular vein is an extremely rare condition. It is
      usually detected during childhood and is characterized by being more prominent
      during Valsalva maneuvers such as vomiting, coughing, and straining. Most of the
      cases reported in the English literature are fusiform aneurysms of the internal
      jugular vein. We report the case of a saccular aneurysm of the left internal
      jugular vein in a 59-year-old woman with no change in size of the aneurysm during
      a Valsalva manuever.

PMID- 17024671
TI  - Giant left atrial myxoma in an elderly patient: natural history over a 7-year
      period.
AB  - We present the case of a 71-year-old woman with a 7-year history of a giant left
      atrial myxoma. The myxoma was attached to the atrial septum and occupied almost
      the entire left atrial cavity. The patient was hospitalized 4 times because of
      dyspnea on exertion, palpitations, fatigue, general asthenia, and weight loss.
      During prior hospitalizations, the patient had refused cardiac surgery. She
      developed several complications, including atrial fibrillation, mitral and
      tricuspid regurgitation, mesenteric embolism, pulmonary edema, and thrombotic
      stroke. We herein describe the natural history of left atrial myxoma in an
      elderly patient over a 7-year period.

PMID- 17024673
TI  - Epiploic appendagitis of the rectosigmoid junction: demonstration with
      transrectal sonography.
AB  - A 24-year-old man presented with lower abdominal pain that had been present for
      18 hours. Physical examination revealed mild tenderness in the lower abdomen.
      Digital rectal examination revealed a tender point approximately 9 cm above the
      anal verge. Transrectal sonographic examination demonstrated an ovoid echogenic
      noncompressible mass surrounded by a hypoechoic halo attached to the wall of the
      rectosigmoid junction. A diagnosis of epiploic appendagitis was made on the basis
      of sonographic findings and was subsequently confirmed with contrast-enhanced CT.

PMID- 17024674
TI  - A rare case of granulomatous prostatitis caused by Mycobacterium tuberculosis.
AB  - We report a rare case of infective granulomatous prostatitis caused by
      Mycobacterium tuberculosis that may be mistaken for prostatic carcinoma, both on
      clinical examination and transrectal sonography (TRUS). A large hypoechoic mass
      was detected in the prostate of a 46-year-old man during TRUS and histopathologic
      examination after TRUS-guided biopsies reported the diagnosis of tuberculous
      prostatitis. We herein describe the clinical and TRUS findings of this case.

PMID- 17024675
TI  - Retained products of conception mimicking a large endometrial AVM: complete
      resolution following spontaneous abortion.
AB  - We report an unusual appearance of retained products of conception that mimicked
      an arteriovenous malformation. A 38-year-old woman presented with persistent
      scant vaginal bleeding and declining levels of serum beta-HCG after therapeutic
      abortion. Sonographic examination revealed a highly vascular lobulated mass,
      which on spectral Doppler examination showed low resistance and high peak
      systolic velocity suggestive of arteriovenous shunting. The patient spontaneously
      passed tissue per vagina, after which the endometrial vascular mass completely
      disappeared, indicating that the sonographic abnormality was the retained
      products of conception. The pathologic basis for such a finding is discussed.

PMID- 17024676
TI  - Is exercise necessary with repetitive nerve stimulation in evaluating patients
      with suspected myasthenia gravis?
AB  - We retrospectively evaluated the effect of exercise on the degree of decrement in
      ulnar, spinal accessory, and facial repetitive nerve stimulation (RNS) in 179
      patients with myasthenia gravis (MG) to assess whether exercise increases the
      diagnostic yield of identifying significant decrements. The mean worsening of
      decrement following exercise was 1.9% (ulnar nerve), 1.9% (spinal accessory
      nerve), and 1.3% (facial nerve). Abnormal (> or =10%) decrement solely following
      exercise occurred in the ulnar nerve in 7% of patients, accessory nerve in 5%,
      and facial nerve in 7%. When analyzed according to Myasthenia Gravis Foundation
      of America class of disease, the likelihood of producing > or =10% decrement only
      after exercise was greatest in class I MG with facial RNS and in class II and III
      generalized MG with ulnar and spinal accessory RNS. In all other disease stages,
      the likelihood of producing > or =10% decrement only after exercise was < or =7%.
      This study suggests that exercise increases the yield of diagnosis of MG by RNS
      in only a small percent of patients. Therefore, in most patients with suspected
      MG, RNS at rest is sufficient and the additional time required for prolonged
      postexercise RNS may be better spent in examining other muscle-nerve
      combinations.

PMID- 17024677
TI  - London taxi drivers and bus drivers: a structural MRI and neuropsychological
      analysis.
AB  - Licensed London taxi drivers show that humans have a remarkable capacity to
      acquire and use knowledge of a large complex city to navigate within it. Gray
      matter volume differences in the hippocampus relative to controls have been
      reported to accompany this expertise. While these gray matter differences could
      result from using and updating spatial representations, they might instead be
      influenced by factors such as self-motion, driving experience, and stress. We
      examined the contribution of these factors by comparing London taxi drivers with
      London bus drivers, who were matched for driving experience and levels of stress,
      but differed in that they follow a constrained set of routes. We found that
      compared with bus drivers, taxi drivers had greater gray matter volume in mid
      posterior hippocampi and less volume in anterior hippocampi. Furthermore, years
      of navigation experience correlated with hippocampal gray matter volume only in
      taxi drivers, with right posterior gray matter volume increasing and anterior
      volume decreasing with more navigation experience. This suggests that spatial
      knowledge, and not stress, driving, or self-motion, is associated with the
      pattern of hippocampal gray matter volume in taxi drivers. We then tested for
      functional differences between the groups and found that the ability to acquire
      new visuo-spatial information was worse in taxi drivers than in bus drivers. We
      speculate that a complex spatial representation, which facilitates expert
      navigation and is associated with greater posterior hippocampal gray matter
      volume, might come at a cost to new spatial memories and gray matter volume in
      the anterior hippocampus.

PMID- 17024678
TI  - Dehydroepiandrosterone sulfate and estrone sulfate reduce GABA-recurrent
      inhibition in the hippocampus via muscarinic acetylcholine receptors.
AB  - Several recent studies have established a role for estrogens in ameliorating
      specific neurodegenerative disorders, mainly those associated with the
      cholinergic neurons of the basal forebrain and their targets in the cortex and
      hippocampus. We have previously demonstrated that endogenous and exogenous
      application of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) markedly
      reduces GABA-mediated recurrent inhibition and synchronizes hippocampal unit
      activity to theta rhythm (Steffensen (1995) Hippocampus 5:320-328). In this
      study, we evaluated the role of muscarinic receptors in mediating the effects of
      DHEAS and estrone sulfate (ES), the principal circulating estrogen in humans, on
      short-latency-evoked potential responses, paired-pulse inhibition (PPI), paired
      pulse facilitation, and GABA interneuron activity in the dentate gyrus and CA1
      subfields of the rat hippocampus. In situ microelectrophoretic application of the
      muscarinic M2 subtype cholinergic receptor agonist cis-dioxolane, DHEAS, and ES
      markedly reduced PPI in the dentate and CA1 that was blocked by the M2 receptor
      antagonist gallamine. Similar to DHEAS, microelectrophoretic administration of ES
      increased population spike amplitudes, without increasing excitatory
      transmission, but this effect was not blocked by gallamine. Microelectrophoretic
      application of cis-dioxolane and ES markedly increased the firing rate of dentate
      hilar interneurons and CA1 oriens/alveus interneurons and enhanced their
      synchrony to hippocampal theta rhythm. These findings suggest that select GABA
      modulating neurosteroids and neuroactive estrogen sulfates alter septohippocampal
      cholinergic modulation of hippocampal GABAergic interneurons mediating recurrent,
      but not feedforward, inhibition of hippocampal principal cell activity.

PMID- 17024679
TI  - Contribution of NR2A and NR2B NMDA subunits to bidirectional synaptic plasticity
      in the hippocampus in vivo.
AB  - It has recently been proposed that activation of the NR2A subunit results in Long
      term potentiation (LTP) induction, whereas activation of the NR2B subunit results
      in long-term depression (LTD) induction. The present study undertakes to
      replicate these findings in vivo to determine if a role for specific subunits in
      synaptic plasticity can be shown in the intact brain. Field recordings were made
      from the CA1 subfield of the hippocampus using Schaffer collateral stimulation in
      anesthetized male Sprague-Dawley rats. Antagonists of the N-methyl-D-aspartate
      receptors NR2A and NR2B subunits were administered by either intraperitoneal
      (i.p.) or intrahippocampal (i.h.) injections to assess their involvement in LTP
      (100 Hz stimuli) and LTD (200 Paired-burst stimuli). i.h. injection of Ro25-6981
      (100 microM) significantly attenuated hippocampal LTP expression and completely
      blocked LTD expression. When administered i.p., Ro25-6981 (6 mg/kg) again blocked
      LTD, but did not significantly diminish the expression of LTP. When NVP-AAM077
      was administered i.h. (80 microM) both LTP and LTD were completely abolished. The
      administration of this compound i.p. (1.2 mg/kg) also significantly attenuated
      LTP, but did not affect LTD. These data suggest that both NR2A and NR2B subunits
      can play roles in LTP and LTD in the hippocampus in vivo.

PMID- 17024682
TI  - Herbert Simon and the GSIA: building an interdisciplinary community.
AB  - This article explores Herbert Simon's attempts to build Carnegie Tech's Graduate
      School of Industrial Administration into a center for interdisciplinary social
      research. It shows that despite the pressures toward disciplinary specialization
      created by the rapid growth of the postwar social sciences, there were strong
      countercurrents supporting interdisciplinary work. Support for interdisciplinary
      work came from a network of powerful new patrons that were interested in
      transforming social science into behavioral science and that supported
      mathematical, behavioral-functional analysis whatever the topic of study. These
      patrons deliberately defined their goals in terms of solving problems, not
      building disciplines, and the networks of advisory committees they created
      enabled certain entrepreneurial researchers, such as Simon, to exert influence
      across a range of fields and institutions.

PMID- 17024683
TI  - Burt's twins: a question of numbers.
AB  - This article estimates the number of monozygotic twins raised apart (MZA)
      potentially available to Cyril Burt in his twin studies. It concludes that
      between 77,000 and 88,000 monozygotic (MZ) twin pairs would have been born and
      survived to the age of ten in the relevant period in England and Wales, and that
      between 750 and 1,750 surviving pairs are likely to have been separated during
      childhood. Burt's claim to have collected 53 MZA pairs is therefore not
      inherently implausible. However, when all the other constraints on Burt's studies
      are taken into account, his numbers are problematic. There are also serious
      difficulties with his claim to have studied 12 pairs born to middle-class
      parents. It is highly improbable that Burt could have located a majority of these
      cases through personal contacts as he claimed.

PMID- 17024684
TI  - Stimulating a normal adjustment: misbehavior, amphetamines, and the
      electroencephalogram at the Bradley Home for children.
AB  - This article uses an historical case study to describe the influence of social
      and contextual factors on the adoption of somatic approaches to children's
      misbehavior. The child guidance movement and the emergence of medicalized
      residential treatment facilities for children influenced the theoretical
      orientations of physicians treating children's behavior disorders in the United
      States in the 1930s. Charles Bradley and his colleagues at the Bradley Home in
      Rhode Island defined behavior disorders in social terms but investigated and
      treated misbehavior with somatic tools. The use of amphetamines and the
      electroencephalogram reorganized concepts of maladjustment along neurological
      lines, even as the research relied on the Home's social priorities.
      Electroencephalographic investigations especially shaped an organic concept of
      misbehavior. Ultimately, the somatic orientation obscured the central role of
      local context in Bradley Home physicians' research.

PMID- 17024685
TI  - Is there a problem with mathematical psychology in the eighteenth century? A
      fresh look at Kant's old argument.
AB  - Common opinion ascribes to Immanuel Kant the view that psychology cannot become a
      science properly so called, because it cannot be mathematized. It is equally
      common to claim that this reflects the state of the art of his times; that the
      quantification of the mind was not achieved during the eighteenth century, while
      it was so during the nineteenth century; or that Kant's so-called "impossibility
      claim" was refuted by nineteenth-century developments, which in turn opened one
      path for psychology to become properly scientific. These opinions are often
      connected, but they are misguided nevertheless. In Part I, I show how the issue
      of a quantification of the mind was discussed before Kant, and I analyze the
      philosophical considerations both of pessimistic and optimistic authors. This
      debate reveals a certain progress, although it remains ultimately undecided. In
      Part II, I present actual examples of measuring the mind in the eighteenth
      century and analyze their presuppositions. Although these examples are limited in
      certain ways, the common view that there was no such measurement is wrong. In
      Part III, I show how Kant's notorious " impossibility claim" has to be viewed
      against its historical background. He not only accepts actual examples of a
      quantitative treatment of the mind, but also takes steps toward an explanation of
      their possibility. Thus, he does not advance the claim that the mind as such
      cannot be mathematized. His claim is directed against certain philosophical
      assumptions about the mind, assumptions shared by a then-dominating, strongly
      introspectionist conception of psychology. This conception did and could not
      provide an explanation of the possibility of quantifying the mind. In concluding,
      I reflect on how this case study helps to improve the dispute over when and why
      psychology became a science.

PMID- 17024686
TI  - Potential of human serum albumin as chiral selector of basic drugs in affinity
      electrokinetic chromatography-partial filling technique.
AB  - The enantiomeric resolution of compounds using HSA by means of affinity EKC
      (AEKC)-partial filling technique is the result of a delicate balance between
      different experimental variables such as protein concentration, running pH
      (background electrophoretic buffer (BGE), protein, and compound solutions), and
      plug length. In this paper, the possibility of using HSA as chiral selector for
      enantioseparation of 28 basic drugs using this methodology is studied. The effect
      of the physicochemical parameters, the structural properties of compounds, and
      compound-HSA protein binding percentages over their chiral resolution with HSA is
      outlined. Based on the results obtained, a decision tree is proposed for the "a
      priori" prediction of the capability of HSA for enantioseparation of basic drugs
      in AEKC. The results obtained indicated that enantioresolution of basic compounds
      with HSA depends on the hydrophobicity, polarity, and molar volume of compounds.

PMID- 17024687
TI  - Enantiomeric separation of underivatized small amines in conventional and on-chip
      capillary electrophoresis with contactless conductivity detection.
AB  - The determination of the enantiomers of small non-UV-absorbing amines which
      otherwise can only be achieved with difficulty was possible by using a
      combination of the chiral crown ether (+)-(18-crown-6)-2,3,11,12-tetracarboxylic
      acid (18C6H4) and dimethyl-beta-CD as selectors in CE and contactless
      conductivity measurement for detection. Alkylamines without any other functional
      group, amino alcohols, species with ether or ester groups and with a cyclic
      moiety were investigated. The detection limits were found to be about 1.0 microM
      and the determination is possible up to at least 1.0 mM. The determination of
      enantiomeric ratios of up to 99.5:0.5 was also found feasible.

PMID- 17024688
TI  - Dynamic unfolding of a regulatory subunit of cAMP-dependent protein kinase by
      capillary electrophoresis: Impact of cAMP dissociation on protein stability.
AB  - Characterization of the unfolding dynamics of a recombinant type IA regulatory
      subunit (RIalpha) of cyclic adenosine monophosphate (cAMP)-dependent protein
      kinase (cAPK) was examined by CE with UV detection. Electrophoretic separation of
      RIalpha by CE in a buffer devoid of cAMP resulted in rapid dissociation of the
      complex from the original sample due to the high negative mobility of the ligand
      relative to receptor. This process enabled in-capillary generation of cAMP
      stripped RIalpha, which was used to estimate the apparent dissociation constant
      (Kd) of 0.6 +/- 0.2 microM. A comparison of RIalpha dynamic unfolding processes
      with urea denaturation was performed by CE with (i.e., RIalpha-cAMP) and without
      (i.e., cAMP-stripped RIalpha) excess cAMP in the buffer during electromigration.
      The presence of cAMP in the buffer confirmed greater stabilization of the
      protein, as reflected by a higher standard free energy change (DeltaG(U) degrees)
      of 10.1 +/- 0.5 kcal x mol(+1) and greater cooperativity in unfolding (m) of 
      2.30 +/- 0.11 kcal x mol(-1) M(-1). CE offers a rapid, yet versatile platform for
      probing the thermodynamics of cAPK and other types of receptor-ligand complexes
      in free solution.

PMID- 17024689
TI  - The impact of NSAID or COX-2 inhibitor use on the initiation of antihypertensive
      therapy.
AB  - PURPOSE: The objective of this study was to quantify the associations between
      NSAIDs and COX-2 inhibitors and risk for initiating antihypertensive therapy.
      METHODS: We conducted a population-based case-control study in a large,
      integrated health system in the Midwestern United States. Cases (N = 23 562) were
      new users of antihypertensive therapy from 1, July 1997, through 31, January
      2003. Controls (N = 23 562) were randomly selected and matched to cases on age,
      copay, medical care utilization, sex, and index date. The main outcome measures
      were exposure to NSAIDs and COX-2 inhibitors. RESULTS: Recent prescription NSAID
      use was associated with an increased risk for initiation of antihypertensive
      therapy (odds ratio (OR) = 1.6, 95%CI 1.5, 1.7) as were selective COX-2
      inhibitors (OR = 1.8, 95%CI 1.6, 2.1). After adjusting for age, sex, co-payment,
      race, and exposure to other NSAIDs/COX-2, each non-selective NSAID (diclofenac,
      ibuprofen, indomethacin, naproxen, oxaprozin) was associated with an increased
      risk of antihypertensive therapy initiation, with ORs ranging from 1.4 to 1.8.
      Recent users of COX-2 inhibitors had an increased risk of initiating
      antihypertensive therapy, regardless of specific drug (celecoxib adjusted OR =
      1.7 (95%CI 1.3, 2.1); rofecoxib adjusted OR = 1.7 (95%CI 1.4, 1.9)). CONCLUSIONS:
      A consistent increased risk of initiation of antihypertensive therapy was
      observed among recent users of NSAIDs and COX-2 inhibitors. Unlike previous
      studies, the results indicate that the effects of rofecoxib and celecoxib are
      equivalent.

PMID- 17024690
TI  - Role of endothelin-1, sodium hydrogen exchanger-1 and mitogen activated protein
      kinase (MAPK) activation in glucose-induced cardiomyocyte hypertrophy.
AB  - BACKGROUND: Cardiac hypertrophy is a key structural feature of diabetic
      cardiomyopathy. Previous studies have shown that diabetes-induced endothelin-1
      (ET-1) and sodium hydrogen exchanger-1 (NHE-1) mediate structural and functional
      deficits in the heart. In order to gain a mechanistic understanding of the role
      of ET-1 and NHE-1 in cardiomyocyte hypertrophy, we have utilized an in vitro
      endothelial-myocyte co-culture system to reveal cellular interactions that may
      arbitrate cardiomyocyte deficits in diabetes. METHODS AND RESULTS: Rat
      ventricular cardiomyocytes were cultured in high glucose levels, which caused
      cellular hypertrophy. Hypertrophic markers, atrial natruritic peptide (ANP) and
      angiotensinogen (Agt), as well as inducible nitric oxide synthase (iNOS) were
      upregulated by high glucose. Treatment of cells with ET antagonist bosentan and
      NHE-1 inhibitor cariporide prevented glucose-induced cardiomyocyte hypertrophy
      and expression of ANP, Agt, and iNOS. Bosentan and cariporide treatment of
      cardiomyocytes co-cultured with endothelial cells produced a more pronounced
      normalization of glucose-induced changes as compared to cardiomyocyte cultured
      alone. To further explore the signaling mechanisms involved, we investigated the
      mitogen activated protein kinase (MAPK) pathway and its cross-interaction with
      signaling proteins known to be altered in diabetes. Our results indicate that
      MAPK activation is associated with cardiomyocyte hypertrophy and is inhibited by
      bosentan, cariporide, as well as protein kinase C inhibiton. Furthermore, MAPK
      activation was found to be upstream of the transcription factors, nuclear factor
      kappaB and activating protein-1. CONCLUSION: These results demonstrate that ET-1
      and NHE-1 may mediate cardiomyocyte hypertrophy via MAPK activation and provide
      an insight into the pathogenesis of diabetic cardiomyopathy.

PMID- 17024691
TI  - Elevation of soluble form of receptor for advanced glycation end products (sRAGE)
      in diabetic subjects with coronary artery disease.
AB  - BACKGROUND: Advanced glycation end products (AGEs)-receptor (RAGE) axis is
      implicated in diabetic vascular complication. Since a soluble form of RAGE
      (sRAGE) could be generated from the cleavage of cell surface RAGE in endothelial
      cells (ECs), serum sRAGE levels may be elevated in diabetes consequent to EC
      damage. In this study, we examined whether sRAGE levels were elevated in type 2
      diabetic patients compared with non-diabetic healthy subjects. METHODS: Serum
      sRAGE levels were examined in 75 Japanese type 2 diabetic patients (29 men and 46
      women; mean age 66 +/- 11 years) and 75 age- and sex-matched non-diabetic healthy
      control subjects. We explored the association between sRAGE levels and coronary
      artery disease (CAD) in diabetic patients. RESULTS: Serum sRAGE levels were
      significantly higher in diabetic patients than in non-diabetic subjects (965.3 +/
      544.2 vs 415 +/- 150.4 pg/mL, p < 0.001). In the univariate analysis, diastolic
      blood pressure (inversely), LDL cholesterol, triglycerides, HDL cholesterol,
      hemoglobin A(1c), and creatinine were significantly associated with sRAGE. After
      performing multivariate analyses, the presence of diabetes (p < 0.0001) was a
      sole independent determinant of sRAGE. Furthermore, there was a significant
      difference in sRAGE levels between diabetic patients with CAD and those without
      CAD (1680.6 +/- 891.1 vs 855.2 +/- 372.1 pg/mL, p < 0.001). Multiple stepwise
      regression analysis revealed that sRAGE and creatinine levels were independent
      determinants of CAD. CONCLUSIONS: The present study demonstrated that serum sRAGE
      levels were significantly higher in type 2 diabetic patients than in non-diabetic
      subjects and positively associated with the presence of CAD.

PMID- 17024695
TI  - Transition-metal anions in solids and their implications on bonding.

PMID- 17024692
TI  - Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes
      patients.
AB  - BACKGROUND: Type 1 diabetes results from a T-cell mediated autoimmune destruction
      of insulin-producing pancreatic beta-cells. The 60-kDa heat-shock protein (hsp60)
      is one of the known target self-antigens. An immunogenic peptide from hsp60,
      p277, arrested beta-cell destruction and maintained insulin production in newly
      diabetic non-obese diabetic (NOD) mice. A randomized, double-blind, phase Ib/II
      study of peptide treatment was undertaken in recent onset type 1 diabetes
      patients with remaining insulin production. METHODS: Forty-eight recent onset
      type 1 diabetes patients were assigned subcutaneous injections of 0.2, 1.0 or 2.5
      mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or
      four placebo injections (n = 12). The primary clinical endpoints were safety and
      efficacy (glucagon-stimulated C-peptide production at 6 and 12 months); secondary
      endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2,
      6, 12 and 18 months. RESULTS: C-peptide levels decreased over time in all groups
      except the 2.5 mg-treated. The decrease in C-peptide production was less in
      treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased
      significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months,
      respectively. No differences were seen in daily insulin doses. One patient was
      withdrawn from the study possibly owing to a treatment-related adverse event.
      CONCLUSIONS: Multiple DiaPep277 peptide administration seems safe and may have a
      beneficial effect on C-peptide levels over time, but this finding is not
      supported by lower HbA1c levels or daily insulin requirement. Further
      investigation on a larger scale is warranted.

PMID- 17024696
TI  - Crystallographic characterization of difluoropropargyl indium bromide, a reactive
      fluoroorganometallic reagent.

PMID- 17024697
TI  - Towards homoleptic naphthalenemetalates of the later transition metals: isolation
      and characterization of naphthalenecobaltates(1-).

PMID- 17024698
TI  - A heterogeneous silica-supported scandium/ionic liquid catalyst system for
      organic reactions in water.

PMID- 17024699
TI  - Selective formation of polycarbonate over cyclic carbonate: copolymerization of
      epoxides with carbon dioxide catalyzed by a cobalt(III) complex with a
      piperidinium end-capping arm.

PMID- 17024700
TI  - Synthesis and structure of a triruthenium complex containing a face-capping
      pyridine ligand.

PMID- 17024701
TI  - Addressing protein flexibility and ligand selectivity by "in situ cross-docking".

PMID- 17024702
TI  - Orbital overlap and chemical bonding.
AB  - The chemical bonds in the diatomic molecules Li(2)-F(2) and Na(2)-Cl(2) at
      different bond lengths have been analyzed by the energy decomposition analysis
      (EDA) method using DFT calculations at the BP86/TZ2P level. The interatomic
      interactions are discussed in terms of quasiclassical electrostatic interactions
      DeltaE(elstat), Pauli repulsion DeltaE(Pauli) and attractive orbital interactions
      DeltaE(orb). The energy terms are compared with the orbital overlaps at different
      interatomic distances. The quasiclassical electrostatic interactions between two
      electrons occupying 1s, 2s, 2p(sigma), and 2p(pi) orbitals have been calculated
      and the results are analyzed and discussed. It is shown that the equilibrium
      distances of the covalent bonds are not determined by the maximum overlap of the
      sigma valence orbitals, which nearly always has its largest value at clearly
      shorter distances than the equilibrium bond length. The crucial interaction that
      prevents shorter bonds is not the loss of attractive interactions, but a sharp
      increase in the Pauli repulsion between electrons in valence orbitals. The
      attractive interactions of DeltaE(orb) and the repulsive interactions of
      DeltaE(Pauli) are both determined by the orbital overlap. The net effect of the
      two terms depends on the occupation of the valence orbitals, but the onset of
      attractive orbital interactions occurs at longer distances than Pauli repulsion,
      because overlap of occupied orbitals with vacant orbitals starts earlier than
      overlap between occupied orbitals. The contribution of DeltaE(elstat) in most
      nonpolar covalent bonds is strongly attractive. This comes from the deviation of
      quasiclassical electron-electron repulsion and nuclear-electron attraction from
      Coulomb's law for point charges. The actual strength of DeltaE(elstat) depends on
      the size and shape of the occupied valence orbitals. The attractive electrostatic
      contributions in the diatomic molecules Li(2)-F(2) come from the s and p(sigma)
      electrons, while the p(pi) electrons do not compensate for nuclear-nuclear
      repulsion. It is the interplay of the three terms DeltaE(orb), DeltaE(Pauli), and
      DeltaE(elstat) that determines the bond energies and equilibrium distances of
      covalently bonded molecules. Molecules like N(2) and O(2), which are usually
      considered as covalently bonded, would not be bonded without the quasiclassical
      attraction DeltaE(elstat).

PMID- 17024703
TI  - "Pocket dendrimers" as nanoscale receptors for bimolecular guest accommodation.
AB  - A new series of dendrimer receptors was prepared by combining a
      (tetraphenylporphinato)zinc(II) core and benzyl ether type dendritic
      substituents. Since one direction of the (tetraphenylporphinato)zinc(II) was not
      substituted by a dendritic residue, the resulting unsymmetrical dendrimers have
      "pockets" available for access of external substrates. Molecular modeling, NMR
      measurements, and zinc-coordination experiments revealed that the third
      generation dendrimer of this type exhibited characteristic inclusion of
      coordinative pyridine guests. When diamidopyridine moiety was introduced into the
      dendrimer pocket, a thymine derivative was bound through complementary hydrogen
      bonding. Two different kinds of substrates, pyridine and thymine derivatives,
      were simultaneously accommodated in the nanoscale pocket and bimolecular guest
      accommodation was realized with the designed dendrimer receptor.

PMID- 17024704
TI  - Exploring base-pair-specific optical properties of the DNA stain thiazole orange.
AB  - Double-stranded DNA offers multiple binding sites to DNA stains. Measurements of
      noncovalently bound dye-nucleic acid complexes are, necessarily, measurements of
      an ensemble of chromophores. Thus, it is difficult to assign fluorescence
      properties to base-pair-specific binding modes of cyanine dyes or, vice versa, to
      obtain information about the local environment of cyanines in nucleic acids by
      using optical spectroscopy. The feasibility to stain DNA and simultaneously probe
      local perturbations by optical spectroscopy would be a valuable asset to nucleic
      acid research. So-called FIT probes (forced intercalation probes) were used to
      pinpoint the location of the DNA stain thiazole orange (TO) in PNADNA duplexes. A
      detailed analysis of the base-pair dependence of optical properties is provided
      and enforced binding of TO is compared with "classical" binding of free TO-PRO1.
      UV-visible absorbance, circular dichroism (CD) and fluorescence spectroscopy, and
      melting-curve analyses confirmed site-specific TO intercalation. Thiazole orange
      exhibited base-specific responses that are not observed in noncovalent dye
      nucleic acid complexes, such as an extraordinary dependence of the TO extinction
      coefficient (+/-60 % variation of the averaged epsilon(max) of 57,000 M(-1) cm(
      1)) on nearest-neighbor base pairs. TO signals hybridization, as shown by
      increases in the steady-state fluorescence emission. Studies of TO fluorescence
      lifetimes in FIT-PNA and in DNADNA and PNADNA complexes highlighted four
      different fluorescence-decay processes that may be closed or opened in response
      to matched or single-mismatched hybridization. A very fast decay process (0.04
      0.07 ns) and a slow decay process (2.33-3.95 ns) provide reliable monitors of
      hybridization, and the opening of a fast decay channel (0.22-0.48 ns) that
      resulted in an attenuation of the fluorescence emission is observed upon the
      formation of mismatched base pairs.

PMID- 17024705
TI  - The Mg-oppenauer oxidation as a mild method for the synthesis of aryl and
      metallocenyl ketones.
AB  - Magnesium alkoxides undergo a hydride-transfer oxidation with benzaldehyde as the
      oxidant. This magnesium variant of the Oppenauer oxidation was used for the
      synthesis of polyfunctional biaryl ketones. LiCl was found to promote this
      reaction by enhancing the solubility of magnesium alkoxides. This mild oxidation
      method was especially useful for preparing ketones bearing a metallocenyl unit as
      well as various new ferrocenyl ketones and tricarbonylchromium complexes. This
      last class of ketones was reduced with the CBS catalyst (CBS=Corey-Bakshi
      Shibata, diphenyl oxazaborolidine) to chiral benzhydrol complexes with high
      enantioselectivity enabling an asymmetric synthesis of electron-rich or -poor
      benzhydryl alcohols (up to 94 % ee).

PMID- 17024706
TI  - Stereoselective preparation of six diastereomeric quatercyclopropanes from
      bicyclopropylidene and some derivatives.
AB  - Diastereomeric meso- and d,l-bis(bicyclopropylidenyl) (5) were obtained upon
      oxidation with oxygen of a higher-order cuprate generated from
      lithiobicyclopropylidene (4) in 50 and 31 % yield, respectively. Their
      perdeuterated analogues meso-[D(14)]- and d,l-[D(14)]-5 were obtained along the
      same route from perdeuterated bicyclopropylidene [D(8)]-3 (synthesized in six
      steps in 7.4 % overall yield from [D(8)]-THF) in 20.5 % yield each.
      Dehalogenative coupling of 1,1-dibromo-2-cyclopropylcyclopropane (6) gave a
      mixture of all possible stereoisomers of 1,5-dicyclopropylbicyclopropylidene 16
      in 69 % yield, from which (Z)-cis-16 was separated by preparative gas
      chromatography (26 % yield). The crystal structure of meso-5 looks like a
      superposition of the crystal structures of two outer bicyclopropylidene units (3)
      and one inner s-trans-bicyclopropyl unit, whereas the two outer cyclopropyl
      moieties adopt a gauche orientation with respect to the cyclopropane rings at the
      inner bicyclopropylidene units in (Z)-cis-16. Birch reduction with lithium in
      liquid ammonia of meso-5 and d,l-5 gave two pairs of diastereomeric
      quatercyclopropanes trans,trans-(R*,S*,R*, S*)-17/cis,trans-(R*,S*,R*,R*)-18 and
      trans,trans-(R*,S*,S*,R*)-19/cis,trans-(R*,S*,S*,S*)-20 in 97 and 76 % yield,
      respectively, in a ratio 9:1 for every pair. The latter diastereomer was also
      obtained as the sole product by Birch reduction of (Z)-cis-16 in 96 % yield.
      Under the same conditions, tetradecadeuterio analogues trans,trans-[D(14)]
      (R*,S*,R*,S*)-17/cis,trans-[D(14)]-(R*, S*,R*,R*)-18 (8:1) and trans,trans
      [D(14)]-(R*,S*,S*,R*)-19/cis,trans-[D(14)]-(R*,S*,S*,S*)-20 (12:1) were prepared
      from meso-[D(14)]-5 and d,l-[D(14)]-5 in 37 and 63 % yield, respectively.
      Reduction of meso-5 with diimine gave the cis,cis-quatercyclopropane
      (S*,S*,R*,R*)-21 as the main product (58 % yield) along with the cis,trans
      diastereomer (S*,S*,R*,S*)-18 (29 % yield). Thus, five of the six possible
      diastereomeric quatercyclopropanes were obtained from meso-5, d,l-5, and (Z)-cis
      16. The X-ray crystal structure analyses of trans,trans-(R*,S*,R*,S*)-17 and
      cis,cis-(S*,S*,R*,R*)-21 revealed for the both an unusual conformation in which
      the central bicyclopropyl unit adopts an s-trans-(antiperiplanar) orientation
      with phi=180.0 degrees , and the two terminal bicyclopropyl moieties adopt a
      synclinal conformation with phi=49.8 and 72.0 degrees , respectively. In solution
      the vicinal coupling constants (3)J(H,H) in trans,trans-(R*,S*,R*,S*)-[D(14)]-17,
      trans,trans-(R*,S*,S*,R*)-[D(14)]-19, trans,cis-(R*,S*,R*,R*)-[D(14)]-18 and
      trans,cis-(R*,S*,S*,S*)-[D(14)]-20 were found to be 4.1, 4.7, 5.9 and 5.9 Hz,
      respectively. This indicates a predominance of the all-gauche conformer in
      (R*,S*,R*,S*)-17 and a decreasing fraction of it in this sequence of the other
      diastereomers.

PMID- 17024707
TI  - Structural and magnetic resolution of a two-step full spin-crossover transition
      in a dinuclear iron(II) pyridyl-bridged compound.
AB  - A dinuclear iron(II) complex containing the new pyridyl bridging ligand, 2,5
      di(2',2''-dipyridylamino)pyridine (ddpp) has been synthesised and characterised
      by single-crystal X-ray diffraction, magnetic susceptibility and Mossbauer
      spectral methods. This compound, [Fe(2)(ddpp)(2)(NCS)(4)]4 CH(2)Cl(2), undergoes
      a two-step full spin crossover. Structural analysis at each of the three plateau
      temperatures has revealed a dinuclear molecule with spin states HS-HS, HS-LS and
      LS-LS (HS: high spin, LS: low spin) for the two iron(II) centres. This is the
      first time that resolution of the metal centres in a HS-LS ordered state has been
      achieved in a two-step dinuclear iron(II) spin-crossover compound.
      Thermogravimetric data show that the dichloromethane solvate molecules can be
      removed in two distinct steps at 120 degrees C and 200 degrees C. The partially
      de-solvated clathrate, [Fe(2)(ddpp)(2)(NCS)(4)]CH(2)Cl(2), undergoes a one-step
      transition with an increased transition temperature with respect to the as
      synthesised material. Structural characterisation of this material reveals subtle
      changes to the coordination geometries at each of the iron(II) centres and
      striking changes to the local environment of the dinuclear complex. The fully de
      solvated material remains high spin over all temperatures. Interestingly, the
      solvent can be re-introduced into the monosolvated solid to achieve complete
      conversion back to the original two-step crossover material,
      [Fe(2)(ddpp)(2)(NCS)(4)]4 CH(2)Cl(2).

PMID- 17024708
TI  - Conformational control of [26]hexaphyrins(1.1.1.1.1.1) by meso-thienyl
      substituents.
AB  - Conformational preference and chemical stability of meso-aryl-substituted
      [26]hexaphyrins(1.1.1.1.1.1) ([26]ArH) depend upon meso-aryl substituents.
      Although only a planar and rectangular conformation (type-II conformation) has
      been identified for [26]ArH so far, we have demonstrated here that a different
      conformation with all the pyrroles pointing inward (type-I conformation) is
      preferred for [26]ArH (7 and 11-I) bearing small 2-thienyl or 3-thienyl
      substituents at 15- and 30-positions. Both type-I and type-II [26]ArH exhibit
      diatropic ring currents, reflecting aromatic character. Type-I [26]ArH, such as 7
      and 11-I, have been shown to serve as an effective ligand for Pd(II) ions to
      provide bis-Pd(II) complexes 12 and 13 with N(3)C(1) coordination through facile
      C--H bond activation.

PMID- 17024709
TI  - Protein glycosylation, conserved from yeast to man: a model organism helps
      elucidate congenital human diseases.
AB  - Proteins can be modified by a large variety of covalently linked saccharides. The
      present review concentrates on two types, protein N-glycosylation and protein O
      mannosylation, which, with only a few exceptions, are evolutionary conserved from
      yeast to man. They are also distinguished by some special features: The
      corresponding glycosylation processes start in the endoplasmatic reticulum, are
      continued in the Golgi apparatus, and require dolichol-activated precursors for
      the initial biosynthetic steps. With respect to the molecular biology of both
      types of protein glycosylation, the pathways and the genetic background of the
      reactions have most successfully been studied with the genetically easy-to-handle
      baker's yeast, Saccharomyces cerevisae. Many of the severe developmental
      disturbances in children are related to protein glycosylation, for example, the
      CDG syndrome (congenital disorders of glycosylation) as well as congenital
      muscular dystrophies with neuronal-cell-migration defects have been elucidated
      with the help of yeast.

PMID- 17024710
TI  - Hormone-PAMAM dendrimer conjugates: polymer dynamics and tether structure affect
      ligand access to receptors.

PMID- 17024711
TI  - Cycloisomerization of 1,6-dienes mediated by Lewis super acids without additives:
      easy access to polysubstituted six-membered carbocycles.

PMID- 17024712
TI  - The changing faces of halogenated marine natural products: total synthesis of the
      reported structures of elatenyne and an enyne from Laurencia majuscula.

PMID- 17024713
TI  - Efficient preparation and catalytic activity of MgO(111) nanosheets.

PMID- 17024714
TI  - Corannulene "hub" carbon coordination by [Ru2{O2C(3,5-CF3)2C6H3}2(CO)5].

PMID- 17024715
TI  - An engineered linker capable of promoting on-resin reactions for microwave
      assisted solid-phase organic synthesis.

PMID- 17024716
TI  - Family income, parenting styles and child behavioural-emotional outcomes.
AB  - A positive relationship between income and child outcomes has been observed in
      data from numerous countries. A key question concerns the extent to which this
      association represents a causal relationship as opposed to unobserved
      heterogeneity. We use data from the National Longitudinal Survey of Children and
      Youth to implement a series of empirical strategies for estimating the existence
      and size of the effect of income on behavioural-emotional outcomes. We also
      examine the role of parenting style. Our results indicate that there is little
      evidence of an effect of income on behavioural-emotional scores. The exclusion of
      parenting style from the models was found to not bias the estimated income
      effect, but parenting style was found to have a consistent impact on child
      outcomes.

PMID- 17024717
TI  - Open-tubular capillary columns with a porous layer of monolithic polymer for
      highly efficient and fast separations in electrochromatography.
AB  - Open-tubular columns for CEC separations having inner-wall coated with a thin
      layer of porous monolithic polymer have been studied. A two-step process
      including (i) UV-initiated polymerization leading to a layer of porous poly(butyl
      methacrylate-co-ethylene dimethacrylate), and (ii) UV-initiated grafting of
      ionizable monomers appear to be well suited for the preparation of these columns.
      The thickness of the porous polymer layer is controlled by the percentage of
      monomers in the polymerization mixture and/or length of the irradiation time. The
      layer thickness significantly affects retention, efficiency, and resolution in
      open-tubular CEC. Under optimized conditions, column efficiencies up to 400,000
      plates/m can be achieved. Use of higher temperature and application of pressure
      enables a significant acceleration of the open-tubular CEC separations.

PMID- 17024718
TI  - AIDS war targets prevention, renews focus on women, blacks.

PMID- 17024719
TI  - Testing. HIV infections diagnosed earlier in New York City.

PMID- 17024720
TI  - HIV testing affirmed for Internet sexual predator.

PMID- 17024721
TI  - CDC issues training package for HIV rapid testing.

PMID- 17024722
TI  - Exposure. HIV illness provides no defense in robbery conviction.

PMID- 17024723
TI  - Funding. Sentence affirmed for AIDS funds embezzler.

PMID- 17024724
TI  - Exposure. Sentence upheld for man who drew blood in fight with police.

PMID- 17024725
TI  - When it's personal.

PMID- 17024726
TI  - Particle separation 2005 - wastewater treatment. Selected papers from the IWA
      International Conference on Particle Separation. June 1-3, 2005. Seoul, Korea.

PMID- 17024727
TI  - The importance of adrenergic receptors in disorders of micturition. 1977.

PMID- 17024728
TI  - The steinstrasse: A legacy of extracorporeal lithotripsy? 1988.

PMID- 17024729
TI  - Angiomyolipoma with cavoatrial extension: Part 2.

PMID- 17024730
TI  - Extinction: the neural mechanisms of behavior change. February 2005. Ponce,
      Puerto Rico.

PMID- 17024731
TI  - The motion: Injectables are justified as a first option for stress urinary
      incontinence.

PMID- 17024732
TI  - Injectables are justified as a first option for stress urinary incontinence:
      Against the motion.

PMID- 17024733
TI  - Bibliography. Current world literature. Pediatric and heritable disorders.

PMID- 17024734
TI  - Bibliography. Current world literature. Osteoarthritis.

PMID- 17024735
TI  - Hepatitis C virus infection and substance abuse. Proceedings of a conference, 11
      13 November 2003, Washington, DC, USA.

PMID- 17024736
TI  - Inhaled carbon and lung function in children.

PMID- 17024737
TI  - Inhaled carbon and lung function in children.

PMID- 17024738
TI  - N-acetylcysteine and contrast-induced nephropathy.

PMID- 17024739
TI  - N-acetylcysteine and contrast-induced nephropathy.

PMID- 17024740
TI  - N-acetylcysteine and contrast-induced nephropathy.

PMID- 17024741
TI  - Iodine nutrition--more is better.

PMID- 17024742
TI  - The new era of medical imaging.

PMID- 17024743
TI  - Periodic pyrexia and malaria in antiquity.

PMID- 17024744
TI  - First national scientific symposium "Risk Management for the Limitation of
      Antibiotic Resistance".

PMID- 17024745
TI  - New international developments towards improved management of non-human use of
      antimicrobials.

PMID- 17024747
TI  - Scientific advisory group on antimicrobials (SAGAM) of the Committee for
      Medicinal Products for Veterinary Use--mandate and work plan.

PMID- 17024746
TI  - Community strategy against antimicrobial resistance.

PMID- 17024748
TI  - Risk management for the limitation of antibiotic resistance--experience of
      Denmark.

PMID- 17024749
TI  - Management recommendations of the Federal Institute for Risk Assessment (BfR)
      after the international BfR symposium "Towards a Risk Analysis of Antibiotic
      Resistance".
AB  - The results of four expert working groups on the risk analysis process on
      antimicrobial resistance are described. They focus on the procedures recommended
      by the FAO/WHO CODEX Alimentarius Commission in 1999 including hazard
      identification, hazard characterization, exposure assessment and risk
      characterization. In all four areas, the current scientific knowledge was
      evaluated and recommendations for risk management options were given. They will
      form the basis for mitigating the health risk due to resistant microorganisms.

PMID- 17024750
TI  - Risk analysis according to the Federal Institute for Risk Assessment
      international symposium "Towards a Risk Analysis of Antibiotic Resistance".
AB  - In the following, the conclusion reached by four expert working groups as
      regarding the aspect of risk assessment in the risk analysis process on
      antimicrobial resistance is outlined. Playing a central role is the procedure,
      which was endorsed by the FAO/WHO CODEX Alimentarius Commission in 1999,
      entailing hazard identification, hazard characterization, exposure assessment and
      risk characterization. Scientific observations in these four areas are subjected
      to evaluation. In essence, risk assessment decisions in this context are
      fundamental as they form the basis for risk management options, which in turn
      should reduce health risks posed by resistant microorganisms.

PMID- 17024751
TI  - Prevention and monitoring: tasks of the federal states in Germany.
AB  - Antimicrobial drugs in livestock farming are not used for therapeutic purposes,
      only, but also to conceal deficiencies in animal husbandry and management. Use of
      antibiotic drugs should be restricted by specific regulations, since some
      veterinarians seem to have an interest in increasing their income by treatment of
      diseases instead of performing health management. The above-mentioned
      requirements have been fulfilled by section 56 a (2) of German Pharmaceuticals
      Act, which regulates the usage and dispensary of pharmaceuticals according to the
      current standards of veterinary science. These current standards of veterinary
      science are described by common scientific positions and specific opinions of
      certain relevant committees. There is no single institutional committee available
      at present. Therefore, members of the German Federal Chamber of Veterinarians and
      members of the Committees of the German Federal States, which are responsible for
      the compliance with regulations and acts, defined a common position on current
      standards of veterinary science, concerning correct treatment with antibiotic
      drugs within a Working Group of the Federal States for Veterinary Pharmaceuticals
      (former ArgeVet, now AG TAM), the so-called "antibiotic guidelines". These
      antibiotic guidelines should help veterinary practitioners to use and prescribe
      those substances only, which are accurate for treatment of the diagnosed disease
      concerning the used class of antibiotic, amount, and duration of usage. The
      responsible authorities have to proof the prudent and proper use of antibiotic
      drugs in the range of their surveillance. The surveillance by the authorities is
      complicated, since the burden of proof of improper usage of antimicrobial drugs
      lies within the responsibility of the authorities. Prevention can primarily be
      conducted by informing the responsible veterinarians of the proper forms of
      treatment and by strict regulations for registration of pharmacologically active
      substances. Every additional label use and the usage of existing old
      registrations may undermine the surveillance of improper usage of
      pharmacologically active substances in livestock animals. The responsible
      authorities of the German Federal States, which may vary in their organization
      among the states, have to administrate the following duties: (1) Surveillance of
      manufacture and distribution of pharmaceuticals. (2) Inspection and control of
      proper usage of pharmaceuticals. Thus, the surveillance of distribution of
      veterinary pharmaceuticals has a broader range of requirements in comparison to
      surveillance of human pharmaceuticals. It is necessary to record and to control
      the amount of used drugs as well as their ways of distribution to perform a
      sufficient surveillance. The legal authorization was created by the 11th
      Amendment of the German Pharmaceuticals Act, but these specifications are still
      too imprecise to support the surveillance in the current process. Hence, the
      actual surveillance process is more focussed on usage and dispensary of
      pharmaceuticals and less focussed on manufacture and distribution. Therefore, the
      current surveillance with the aim to limit unnecessary usage of pharmacologically
      active substances according to the current legislation is limited. It is
      necessary to change legislation with regard to control of distribution of
      pharmaceuticals as well as integration of self-control of livestock owners for a
      sustainable increase of efficacy.

PMID- 17024752
TI  - The impact of the CVMP antibiotic guidelines on research and development of
      antibiotics.

PMID- 17024753
TI  - Monitoring of antimicrobial resistance on the basis of the E.U. Zoonoses
      Directive.
AB  - The new zoonoses Directive 2003/99/EC gives the opportunity for an improvement in
      the harmonization of antimicrobial resistance testing of zoonotic agents. The
      current reporting system under Council Directive 92/117/EEC was a voluntary
      approach leading to a limited comparability of the data. In the directive
      2003/99/EC, inforced since June 2004, antimicrobial susceptibility testing is
      part of the legislation. The benchmarks, the zoonotic agents Salmonella spp. and
      Campylobacter spp., the animal species cattle, pigs and poultry, as well as
      products thereof are fixed. In this paper details for a harmonized monitoring
      scheme are proposed. The draft specifies in more detail the animal species, the
      production lines and the locations of the sampling. The sampling frame should
      ensure a representative number of isolates to meet the objectives, these are
      detection of occurrence of resistance patterns, estimation of the prevalence of
      resistance to an antimicrobial substance, and assessment of changes in the
      prevalence of antimicrobial resistance. Apart from isolates from monitoring
      schemes reflecting the healthy animal population, clinical isolates should be
      included to detect new emerging resistance genes. The comparability of the
      methods applied has to be ensured by an external quality assurance system. As the
      monitoring of antimicrobial resistance should be closely linked to the monitoring
      programs laid down in the directive 2003/99/EC to estimate the prevalence of
      zoonotic agents along the food chain. A stepwise implementation in accordance
      with the other monitoring programs is suggested. In order to support management
      decisions to limit the emergence and spread of resistance additional information
      has to be collected, i.e. resistance in animal pathogens, usage of
      antimicrobials, or the relevance of the import of animals or products of animal
      origin.

PMID- 17024754
TI  - Management options with the regard to authorization of antibiotics in veterinary
      medicine.

PMID- 17024755
TI  - Impact of German National Reference Centres on monitoring of antibiotic
      resistance.
AB  - Currently 15 National Reference Centres (NRCs) and 59 associated consiliary
      laboratories make up the "infection and epidemiological network" of the Robert
      Koch-Institute (RKI), Berlin. Every 3 years evaluation of the NRCs by independent
      assessors determines, whether funding by the RKI will be continued or new
      applications for NRCs will be considered. Central tasks of the NRCs are (i) the
      development, improvement, and standardization of diagnostic methods, (ii)
      diagnosis and molecular epidemiological typing of outbreak-related pathogens,
      (iii) establishment and maintenance of a collection of reference strains, (iv)
      advisory service for diagnostic routine laboratories, (v) collaborations with
      other European reference centres and WHO reference laboratories, if applicable,
      (vi) collaboration with and support of the RKI in case of epidemiological studies
      and surveillance projects, (vii) active support of the RKI outbreak investigation
      task force, and (viii) surveillance and epidemiological analysis of development
      of pathogen virulence and antimicrobial resistance. The following section focuses
      on monitoring of resistance of bacterial pathogens of special importance in
      particular NRCs, especially those dealing with bacterial infections.

PMID- 17024756
TI  - Resistance monitoring of human pathogenic bacteria in Germany, SWOT analysis and
      examples.
AB  - Determination of antibiotic resistance has two main goals in clinical
      microbiological diagnosis. One aspect is preservation of antibacterial
      chemotherapy. Furthermore, trends in resistance development should be monitored
      and should serve as an early warning-system for occurrence and spread of new and
      clinically important antibiotic resistances. Plenty of data on antibiotic
      resistance is gathered on a routine basis in medical-microbiological diagnosis
      and often it is stored in electronic databases that could be interlinked. The
      main reason that the available data is not being used for resistance monitoring
      in Germany is the widely used methodology of the agar diffusion test. It is the
      cheapest and by far the most inaccurate method of determining resistance. The
      test results are not always comparable with tests for all substance groups from
      national standards (also limited international comparability). Trend analysis of
      the resistance situation in Germany can therefore only be determined through
      individual studies. These studies are discussed according to a SWOT analysis
      (SWOT = Strengths, Weaknesses, Opportunities, Threats).

PMID- 17024757
TI  - Detection of occult sentinel lymph node micrometastases by immunohistochemistry
      in breast cancer. An NSABP protocol B-32 quality assurance study.
AB  - BACKGROUND: Occult metastases, by definition, are not detected on initial
      examination. They may be present on slides but missed during screening or may be
      present in paraffin embedded tissue blocks and undetected without additional
      levels. Anticytokeratin immunohistochemistry (CK IHC) enhances detection of
      occult metastases, particularly micrometastases (> 0.2 mm but not larger than 2.0
      mm) or isolated tumor cell clusters (< or = 0.2 mm). This study defines the rate
      at which pathologists miss metastases on CK IHC of sentinel lymph nodes (SLN).
      METHODS: CK IHC sections 0.5 and 1.0 mm from the original surface of SLN tissue
      blocks were screened by pathologists using standard bright field light
      microscopes (LM) and by supervised computer assisted cell detection (CACD). All
      blocks were from breast cancer patients, initially classified 'node negative' on
      review of routinely stained sections from the surface of each block. Cases missed
      by LM screening but detected by CACD defined false negative screens. RESULTS: Of
      236 cases screened, LM detected 34 (14.4%; 95% CI: 9.6-20.2) cases and, in the
      202 cases negative by LM, CACD detected an additional 30 (14.9%; 95% CI: 9.6
      21.2%) cases with occult metastases. Occult metastases missed by LM screening
      ranged from 0.01 to 0.1 mm in greatest dimension. The probability of missing an
      occult metastasis < or = 0.02 mm; < or = 0.05 mm, and < or = 0.10 mm was 75%,
      69.2%, and 61.2%, respectively. No occult metastases larger than 0.10 mm were
      missed by LM screening. CONCLUSIONS: Pathologists screening the CK IHC stained
      slides may frequently miss detecting metastases < 0.10 mm.

PMID- 17024758
TI  - Prognostic variability among nonsmall cell lung cancer patients with pathologic
      N1 lymph node involvement. Epidemiological figures with strong clinical
      implications.
AB  - BACKGROUND: Patients who have nonsmall cell lung cancer with N1 lymph node status
      are an intermediate group of patients who have a variable prognosis. Differences
      in lymph node level (hilar or pulmonary lymph nodes) may influence patient
      survival. The authors retrospectively analyzed the factors that influenced
      prognosis, including the level of N1 lymph node involvement. METHODS: The authors
      used the Tuscan Cancer Registry archives to retrieve records on 2523 patients who
      had lung tumors diagnosed during the period from 1996 and 1998 in the provinces
      of Florence and Prato, central Italy. To analyze the survival of patients
      according to the level of lymph node involvement, the prognoses of patients with
      nonsmall cell lung cancer who had N1 lymph node status were compared in a
      population-based case series. Among 112 patients with pathologic N1 status, the
      following variables were analyzed for their influence on postoperative survival:
      gender, age, cell type, pathologic tumor status, the number of metastatic lymph
      nodes, the level of metastatic lymph nodes (hilar or pulmonary), and the type of
      surgical resection. RESULTS: The 5-year survival rates for patients who had
      involvement of pulmonary and hilar lymph nodes were 41.2% and 21.8%, respectively
      (P =.005). A Cox proportional hazards model analysis indicated that the presence
      of hilar lymph node involvement was an independent prognostic factor.
      CONCLUSIONS: N1 pathologic lymph node status was identified in a combination of
      subgroups with different prognoses, and the presence of hilar lymph node disease
      had prognostic significance. This difference in survival may lead to the use of
      different therapies for these subgroups of patients with pathologic N1 non-small
      cell lung cancer.

PMID- 17024759
TI  - Creating a registry for patients with chronic disease.

PMID- 17024760
TI  - Which drugs to prescribe.

PMID- 17024761
TI  - Once-daily dosing and the treatment of HIV disease.

PMID- 17024762
TI  - HIV patients often unaware of drug resistance.

PMID- 17024763
TI  - Policy watch. Turning op-ed into policy.

PMID- 17024764
TI  - AIDS 25 years later: routinizing HIV testing.

PMID- 17024765
TI  - Kawasaki-like syndrome possibly associated with immune reconstitution
      inflammatory syndrome in an HIV-positive patient.
AB  - The occurrence of Kawasaki disease is unusual in adults. We report a Kawasaki
      like syndrome in a middle-aged HIV-positive man who had recently begun effective
      antiretroviral therapy. Onset of a significant inflammatory response after
      initiation of antiretroviral therapy prompted a diagnosis of Kawasaki-like
      syndrome associated with immune reconstitution inflammatory syndrome.

PMID- 17024766
TI  - Enfuvirtide: patient acceptance and strategies for managing injection-site
      reactions.
AB  - Enfuvirtide is a virologically and immunologically active, injectable
      antiretroviral fusion inhibitor developed for the treatment of HIV infection.
      Patients have shown high adherence rates related to self-preparation
      (reconstitution) and self-administration of enfuvirtide. This review discusses
      the efficacy and acceptability of enfuvirtide and offers advice to help health
      care professionals and patients address concerns about self-injection. Practical
      interventions that can help minimize and manage the impact of injection-site
      reactions are described, including the use of a needle-free device for
      administering the drug.

PMID- 17024767
TI  - Addressing the need for HIV specialists: the AAHIVM perspective.
AB  - HIV medicine is a complex and rapidly changing field that requires experienced
      care providers. Clinical research has shown what has always been intuitive:
      providers with more experience have patients with better outcomes, and the
      resultant decrease in morbidity, mortality, and inpatient costs of expert care
      are cost-effective. As a result, there is a need to identify providers who can
      give the best quality care to persons living with HIV/AIDS. The American Academy
      of HIV Medicine has established a credentialing process to identify HIV
      specialists who demonstrate continuing competency in key aspects of HIV medicine
      from among a broad range of HIV health care providers. Several other
      organizations have attempted to identify qualified HIV medical providers but
      differ in key aspects of their definition of an HIV expert, with differing
      effects on the quality of health care delivered to persons living with HIV/AIDS.
      There is a need for all interested parties to come together to find solutions; to
      address the need for, and barriers to, increasing the number of HIV specialists;
      and to come to a consensus about the best way to ensure quality care for all
      those living with HIV/AIDS.

PMID- 17024768
TI  - Editorial comment: the need for alternative credentialing system for HIV.

PMID- 17024769
TI  - Therapeutic issues and the relationship to the deceased: working clinically with
      the two-track model of bereavement.
AB  - Psychological intervention with the bereaved can provide critical assistance to
      individuals, families, and communities contending with the loss of significant
      others. In the organizational paradigm of the Two-Track Model of Bereavement, the
      outcome of both successful and problematic mourning are manifest along two
      distinct but interrelated tracks of functioning and relationship to the deceased.
      Reworking relationships to the deceased can help people resume authorship of
      their life narratives following loss. Two cases of spousal death are presented
      and significant features of the treatments discussed. The Two-Track Model of
      Bereavement emphasizes that the dimensions of a person's functioning reflect only
      part of the response to loss. The ongoing relationship with the complex of
      memories, thoughts, emotions, and needs associated with the person who has died
      is no less important. Although the domains of general functioning and
      relationship to the deceased are related, they are far from identical. Attending
      to the memories and emotions bound up with the deceased should continue to demand
      our sustained attention as therapists.

PMID- 17024771
TI  - [Abstracts of 54th annual scientific session of the Japanese College of
      Cardiology. Kagoshima, Japan. September 25-27, 2006. Abstracts].

PMID- 17024770
TI  - Avian influenza, Indonesia--update.

PMID- 17024772
TI  - [59th Annual meeting of the Japanese Association for Thoracic Surgery. Tokyo,
      Japan. October 1-4, 2006. Abstracts].

PMID- 17024773
TI  - Wound healing: a rose in the desert.

PMID- 17024774
TI  - [Question and answer of PET facilities: Part 1].

PMID- 17024775
TI  - Evans v. Amicus Healthcare Ltd; Hadley v. Midland Fertility Ltd.

PMID- 17024776
TI  - Pain from skin and wound conditions. Part 1.

PMID- 17024777
TI  - Softening the pain of cancer-related wounds.

PMID- 17024778
TI  - Re R (a Child).

PMID- 17024779
TI  - Using education to increase self-care for the person with an ostomy.

PMID- 17024780
TI  - Nourishing mind, body, and soul.

PMID- 17024781
TI  - The Queen (on the application of Smeaton) v. Secretary of State for Health.

PMID- 17024782
TI  - [Osteoporosis-induced fractures: what therapeutic possibilities are available?].

PMID- 17024783
TI  - Parental grief following the brain death of a child: does consent or refusal to
      organ donation affect their grief?
AB  - The purpose of this study was to investigate the grieving process of parents who
      were faced with the dilemma of donating organs and tissues of their underage
      brain dead child, and to explore the impact of their decision on their grief
      process. A grounded theory methodology was adopted and a semi-structured
      interview was conducted with 11 bereaved parents who consented to, and 11 parents
      who declined organ donation. Findings suggest that the core themes that
      characterize their grief and the main variables that affect their grieving
      process are similar for both donor and non-donor parents. Consent or refusal of
      organ donation per se does not seem to affect the overall grieving process. It is
      the meaning attributed to the act of donation that affects how parents perceive
      the child's death and subsequently facilitate or hinder their adjustment to loss.

PMID- 17024784
TI  - [What do you see? Visceral tuberculosis].

PMID- 17024785
TI  - Differential dimensions of death anxiety in nursing students with and without
      nursing experience.
AB  - Researchers have demonstrated death anxiety in nursing professionals; however, it
      is unclear as to when this anxiety develops. This study used a multidimensional
      measure to investigate death anxiety in a group of experienced (n = 53) and
      inexperienced (n = 49) nursing students and a control group of non-nursing
      students (n = 50). Experienced nursing students reported significantly more fear
      of the dying process than inexperienced nursing students and controls whereas
      both experienced and inexperienced nursing students reported more fear of the
      unknown than controls. The results suggest that death anxiety may develop early
      in a nurse's training.

PMID- 17024786
TI  - College student suicide: a call to action.
AB  - This article examines current issues related to the topic of college student
      suicide and why it continues to be an issue of major concern. The nature/extent
      of the problem, risk and protective factors, responses to college student
      suicide, legal issues, and training issues are discussed. The importance of
      addressing the issue of college student suicide and its prevention on college
      campuses is emphasized as is the importance of protective factors. Although more
      is being done to address this issue than has been done in the past, it remains a
      major concern, and it is an issue that requires a strong national response.

PMID- 17024787
TI  - Personal reflections of funeral rituals and spirituality in a Kentucky African
      American family.
AB  - This article introduces the authors' experiences and observations as
      grief/bereavement counselors participating in urban and rural funerals. A
      vignette illustrates the use of rituals and spirituality of one African American
      family, living in a rural area of Kentucky, and their efforts to cope with their
      own grief and loss of a loved one. The article describes why it is important for
      professional practitioners to have awareness about a range of diverse funeral
      events and traditions that can take place in the African American community.
      Funeral practices and customs are discussed as well as suggestions for culturally
      competent practice in working with those who have experienced loss and grief.

PMID- 17024788
TI  - Fungal pneumonia due to molds in patients with hematological malignancies.
AB  - Invasive fungal infections are an important cause of morbidity and mortality in
      patients with hematological malignancies. In particular, patients with
      neutropenia and those who have undergone allogeneic hematopoietic stem cell
      transplantation are at highest risk, with fungal pneumonia being the main
      clinical manifestation in these patients. The most common pathogens associated
      with fungal pneumonia are Aspergillus spp. and Zygomycetes. However, other
      pathogens have also been observed in fungal pneumonia, including Cryptococcus
      spp., Pneumocystis jirovecii, and Candida spp. This comprehensive review will
      focus on the important practical aspects relevant to the epidemiology, clinical
      diagnosis, and therapeutic management of pneumonia due to filamentous fungi in
      patients affected by hematological malignancies.

PMID- 17024789
TI  - Diversity of structures carrying the aac(6')-aph(2") gene in clinical
      Enterococcus faecalis and Enterococcus faecium strains isolated in Tunisia.
AB  - The diversity of structures carrying the aac(6')-aph(2") gene was studied in 46
      high-level gentamicin-resistant Enterococcus faecalis and Enterococcus faecium
      clinical strains recovered in a Tunisian hospital during the period 2000-2003.
      The inclusion of the aac(6')-aph(2") gene within the Tn4001 composite element or
      in its truncated forms (lacking the IS256 at the right, the left or at both sides
      of the aac(6')-aph(2") gene) was investigated by PCR and sequencing. The aac(6')
      aph(2") gene was included in the composite Tn4001 element in 19 of 34 high-level
      gentamicin-resistant E. faecalis strains (56%) and in 1 of 12 E. faecium strains
      (12%). A truncated form of Tn4001 lacking IS256 at the left-hand (in 10 E.
      faecalis and 8 E. faecium), at the right-hand (3 E. faecalis and 2 E. faecium) or
      at both sides of the aac(6')-aph(2") gene (in 2 E. faecalis and 1 E. faecium) was
      also detected in 26 of our enterococci. The transference by conjugation of the
      aac(6')-aph(2") gene, associated with other resistance genes, was demonstrated in
      seven of the high-level gentamicin-resistant E. faecalis strains.

PMID- 17024790
TI  - Restoration of oxacillin susceptibility in methicillin-resistant Staphylococcus
      aureus by blocking the MecR1-mediated signaling pathway.
AB  - The signal transducing integral membrane protein, MecR1 helps initiate the
      expression of the antibiotic-resistant gene mecA, which encodes the penicillin
      binding protein 2a. MecA participates in the beta-lactam resistance of
      methicillin-resistant Staphylococcus aureus (MRSA). Blocking the MecR1 regulatory
      pathway may be a novel strategy to combat MRSA. In this study, we introduced an
      antisense phosphothioate oligodeoxynucleotide (PS-ODN) targeting MecR1 mRNA into
      the MRSA strain WHO-2, which led to a significant reduction of both MecR1 and
      PBP2a mRNAs in a concentration-dependent manner. Consequently, the susceptibility
      of S. aureus WHO-2 to the beta-lactam antibiotic oxacillin was restored
      significantly. Our results indicate that blocking the mecR1-mecI-mecA signaling
      pathway via an antisense approach might be a viable strategy to restore the
      susceptibility of MRSA to the existing beta-lactam antibiotics.

PMID- 17024791
TI  - Application of two methods to determine killing of Streptococcus pneumoniae by
      various fluoroquinolones.
AB  - Minimum inhibitory concentration (MIC) testing measures the lowest drug
      concentration that prevents microbial growth using an inoculum of 10(5) colony
      forming units/ml (cfu/ml) whereas the mutant prevention concentration (MPC)
      (inoculum approximately 10(10) cells) defines the antimicrobial drug
      concentration threshold that would require an organism to possess two
      simultaneous mutations for continued growth in the presence of the drug. The
      rates at which multidrug-resistant Streptococcus pneumoniae [MDRSP] were killed
      by the respiratory fluoroquinolones, gatifloxacin, gemfloxacin, levofloxacin and
      moxifloxacin, were compared based on the MIC and MPC drug concentrations and at
      inocula ranging from 10(6)-10(9) cfu/ml. The MIC drug concentration failed to
      eradicate all viable cells whereas the MPC drug concentration resulted in 99.9%
      to 100% cellular reduction following 12-24 hours of drug exposure. MPC values
      against S. pneumoniae were different for each fluoroquinolone. The MPC drug
      concentration prevents the selection of multidrug-resistant or fluoroquinolone
      resistant S. pneumoniae. The value of dosing of antimicrobial agents based on MPC
      thresholds results in a rapid reduction in viable cells--even at higher inocula
      which are more reflective of organism burden in pneumonia. The rapid reduction in
      viable cells observed at MPC drug concentrations may not only have an impact on
      preventing the selection of resistant mutants but may also help explain the rapid
      symptom resolution seen with new fluoroquinolones since these agents lead to
      little or low release of cell contents which are known to drive the inflammatory
      response.

PMID- 17024792
TI  - Relative potential for selection of quinolone-resistance-determining-region
      mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and
      moxifloxacin.
AB  - Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence
      of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates.
      Non-susceptibility as defined by Clinical and Laboratory Standards Institute
      (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with
      gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and
      gatifloxacin selected for a single step quinolone-resistant-determining-region
      (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas
      gemifloxacin selected simultaneously for multi-step mutations in gyrase and
      topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux
      mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe
      and Glu-85-Lys in GyrA and Ser-79-Phe or Asp-83-Tyr in ParC. At high MICs,
      moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well
      as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2-
      to 16-fold greater activity than moxifloxacin or gatifloxacin against strains
      with two or more QRDR mutations, however, its potency did not translate to
      nonsusceptibility and gemifloxacin MIC values were either at or well above the
      CLSI nonsusceptible breakpoint concentration.

PMID- 17024793
TI  - In vitro induction of resistance by tissue concentrations of azithromycin,
      clarithromycin, cefixime and amoxicillin/clavulanate in clinical isolates of
      Streptococcus pyogenes.
AB  - This study evaluated the effects of exposure to serum, tonsils and breakpoint
      drug concentrations of clarithromycin, azithromycin, cefixime and
      amoxicillin/clavulanate on Streptococcus pyogenes susceptibility. Frequency of
      mutation and development of resistance after ten passages on antibiotic gradient
      plates, followed by ten passages without antibiotic, were determined. Phenotypes
      of macrolide-resistant strains grown at the end of multi-step selection were also
      determined. Azithromycin induced a surge of resistant strains more rapidly and
      frequently than clarithromycin, particularly at tonsils concentrations. With
      amoxicillin/clavulanate no strains showed minimum inhibitory concentrations
      (MICs) higher than the susceptibility breakpoint. Mutational frequencies were
      higher for azithromycin, at serum and breakpoint drug concentrations, than for
      the other drugs. Most of the macrolide resistant strains showed an MLS(B)
      phenotype. In conclusion, the ability to prevent the occurrence of resistance in
      clinical isolates of S. pyogenes was similar for amoxicillin/clavulanate and
      clarithromycin followed by cefixime > azithromycin when tonsil drug
      concentrations were considered, and greater for amoxicillin/clavulanate followed
      by clarithromycin > cefixime> azithromycin, at breakpoint and serum
      concentrations.

PMID- 17024794
TI  - Antimicrobial susceptibility of Streptococcus pyogenes and Streptococcus
      pneumoniae: surveillance from 1993 to 2004 in Central Italy.
AB  - The susceptibility of 1870 Streptococcus pyogenes and 1595 Streptococcus
      pneumoniae to macrolides and lincosamides has been monitored from 1993 to 2004 in
      Central Italy. Among S. pyogenes, 30.2% were erythromycin resistant; 18.5% were
      also resistant to josamycin and clindamycin (MLS phenotype). After an increasing
      erythromycin resistance rate in 1993-1997 (maximum 53.16%), a definite decrease
      was observed since 2001 with resistance rates always less than 30%. Thirty six
      percent of pneumococcal isolates were erythromycin-resistant, with minor temporal
      fluctuations; the MLS phenotype was the most prevalent overall (32.6%) and in
      individual years. S. pneumoniae strains were also tested for susceptibility to
      beta-lactams and other antimicrobial agents: 11.2% were penicillin non
      susceptible, with a gradually increasing prevalence after 2001 (maximum rate
      17.3% in 2004), 31.15% were resistant to tetracycline, 4.9% to chloramphenicol,
      0.74% to rifampin. All pneumococcal isolates were susceptible to teicoplanin and
      99.9% to ceftriaxone and ofloxacin.

PMID- 17024795
TI  - Surveillance of monthly antimicrobial consumption rates stratified by patient
      care area: a tool for triggering and targeting antibiotic policy changes in the
      hospital.
AB  - The profile and temporal trends of antimicrobial use were investigated at a
      university hospital. Aggregate data were analyzed according to the ATC/DDD
      methodology. During 1998-2002, hospital-wide antimicrobial use increased by 22%,
      from 86.97 to 106.24 defined daily doses per 100 bed-days [DDD/100BD]. Pooled
      usage rates in DDD/100BD, overall percentage increases and annual average
      increase rates were respectively 109.97, 35.6%, 8.1 for Medical wards, 98.21,
      48.7%, 9.1 for Intensive Care Units and 74.46, 34.3%, 5.7 for Hemato-oncology
      wards. Surgical wards had a fairly constant usage rate (98.36). A shift towards
      the newer broad-spectrum antibiotics, to the detriment of the older penicillins
      and cephalosporins, was noted in all hospital areas. Surveillance of
      antimicrobial consumption using the ATC/DDD system provided a clear picture of
      its profile. Monthly rates over a sufficient surveillance period allowed the
      assessment of temporal trends. Stratification of rates according to clinical
      service allowed areas of concern to be specified and targeted antibiotic policy
      changes to be initiated.

PMID- 17024796
TI  - Risk factors for postoperative chest wound infections due to gram-negative
      bacteria in cardiac surgery patients.
AB  - Gram-negative bacteria account for up to 35% of postoperative sternal wound
      infections (SWI) in patients undergoing cardiac surgery. Despite this, risk
      factors for Gram-negative SWI have not been investigated. The objective of this
      study was to define risk factors associated with Gram-negative SWI in patients
      undergoing cardiac surgery. 2590 patients undergoing cardiac surgery between 2002
      2005 were prospectively monitored for development of SWI. Patient, operative, and
      post-operative risk factors were compared among patients that developed Gram
      negative SWI and Gram-positive SWI to uninfected controls using univariate and
      multivariate analysis. A p < 0.05 was considered significant. Surgical site
      infections developed in 152 (5.9%) patients. Isolates were recovered from the
      sternum for 128 (5.0%) patients, from the leg donor site for 19 (0.73%) patients,
      and from the sternum and donor site for 5 (0.19%) patients. Gram-positive
      pathogens were isolated from 83 (3.3%) patients, Gram-negative pathogens from 42
      (1.6%) patients, and mixed pathogens from 27 (1.0%) patients. Hospital admission
      greater than 48 hours before surgery (OR: 2.25; 95% CI: 1.11 - 4.58), ventilator
      dependency preoperatively (OR: 5.32 95% CI: 2.22 - 12.75), and thoracentesis
      procedure postoperatively (OR: 3.71; 95% CI: 1.45 - 9.49) and diabetes (OR: 2.04;
      95% CI: 1.17 - 3.55) were identified as significant risk factors for SWI due to
      Gram-negative bacteria using multivariate logistic regression. Diabetes,
      increased age, and peripheral vascular disease were identified as significant
      risk factors for SWI due to Gram-positive bacteria (p < 0.05, each). The risk
      factors associated with Gram-negative SWI differed significantly from those
      associated with Gram-positive SWI. Risk factors associated with Gram-negative SWI
      were identified. Unique interventions may be necessary to prevent Gram-negative
      SWI in cardiac surgery patients.

PMID- 17024797
TI  - Topical kanamycin: an effective therapeutic option in aerobic vaginitis.
AB  - Eighty-one patients with clinical diagnosis of aerobic vaginitis (AV) were
      included in the study. The patients were randomized for treatment, 45 with
      kanamycin (100 mg vaginal ovules for 6 days, consecutively) and 36 with
      meclocycline (35 mg vaginal ovules for 6 days, consecutively). The patients were
      examined before starting the study, 1-2 days after treatment and 30 days after
      the end of the study. At the first follow-up the patients showed different levels
      of symptom reduction. Reduction in the presence of leukocytes, vaginal mucosa
      burning and itching were statistically significant in the group treated with
      kanamycin with respect to the group treated with meclocycline. Moreover, there
      was also reduced isolation of Enterobacteriaeae (97%) in the group treated with
      kanamycin versus those treated with meclocycline (76%). At the second follow-up,
      vaginal homeostasis (normalization of pH and presence of lactobacilli) was more
      evident in the kanamycin-treated group. In conclusion, our data suggest that the
      topical use of kanamycin could be considered a specific antibiotic for the
      therapy of this new pathology.

PMID- 17024798
TI  - Synergistic effects of valproic acid and mitomycin C in adenocarcinoma cell lines
      and fresh tumor cells of patients with colon cancer.
AB  - Valproic acid has been demonstrated to mediate cytotoxic effects against tumor
      cells by acting as a histone-deacetylase inhibitor. However, to date, there are
      only limited data on the effects of valproic acid in colon cancer. Moreover,
      information regarding combinations of the drug with chemotherapeutic agents is
      very limited. The latter is of interest as there is increasing evidence for
      synergism between so-called "molecular targeting drugs" and chemotherapy. We
      first demonstrated that valproic acid dose-dependently reduced the viability of
      adenocarcimona cell lines. After co-incubation with a variety of chemotherapeutic
      agents, only valproic acid in combination with mitomycin C consistently induced
      synergistic growth inhibition in all cell lines. To confirm these results in an
      ex vivo situation, five samples of fresh colon cancer cells were studied. Again,
      the effect of valproic acid on the viability of the fresh tumor cells was dose
      dependent. In four of five samples of freshly isolated colon cancer cells, the
      synergistic effect of valproic acid and mitomycin C on the inhibition of cell
      growth was confirmed by calculation of the combination index by multiple drug
      effect analysis. In conclusion, this is the first demonstration that valproic
      acid as a model substance for histone-deacetylase inhibitors is effective in
      tumor cells freshly isolated from patients with colon cancer and that the
      combination of mitomycin C and valproic acid synergistically decreases viability
      of colon cancer cells.

PMID- 17024799
TI  - Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients.
AB  - Tamoxifen has been reported to potentiate the anticoagulant effect of warfarin
      and also to increase the plasma level of phenytoin, which are mainly metabolized
      by CYP2C9. The aim of this study was to determine the influence of tamoxifen on
      CYP2C9 activity in vivo in humans. Thirteen breast cancer patients who would
      start tamoxifen following cytotoxic chemotherapy were enrolled in the study. A
      single oral dose of 25 mg losartan was given to the patients 2 days before and 2
      weeks after starting tamoxifen therapy. Losartan and E3174 in 8-hour urine
      samples were measured by HPLC. Tamoxifen significantly increased the average
      urinary losartan/E3174 ratio from 0.73 (CI 95% = 0.15 - 2.30) to 1.66 (CI 95% =
      0.68 - 5.20), after 2 weeks of treatment (p = 0.002). Tamoxifen inhibited CYP2C9
      activity in breast cancer patients within two weeks of its administration. The
      inhibition of CYP2C9 activity may be a possible explanation for the drug-drug
      interaction of tamoxifen with CYP2C9 substrates.

PMID- 17024800
TI  - Treatment of post-traumatic hand Staphylococcus aureus osteomyelitis with oral
      linezolid.
AB  - The Authors report on the use of linezolid for the treatment of three patients
      with osteomyelitis. All three patients had post-traumatic multisensitive hand
      bone methicillin-susceptible Staphylococcus aureus osteomyelitis, which did not
      respond to antimicrobial regimens including drugs in vitro active against the
      isolated strains. Clinical cure and microbiologic eradication was obtained with
      oral linezolid in all three patients. Linezolid was well tolerated. Mild
      thrombocytopenia was observed in one patient at the end of the third week of
      treatment and it was promptly resolved after the discontinuation of linezolid.
      Linezolid minimum inhibitory concentrations (MICs) consisted of 2 mg/l for all
      three S. aureus isolates while the bactericidal activity in vitro was not present
      up to the linezolid concentration of 32 mg/l. In spite of a lack of in vitro
      bactericidal activity, linezolid was effective in curing the patients and
      eradicating the infection. Trough and peak plasma concentrations of linezolid
      were above the MICs of the isolates. These values ranged from 3.93 to 14.95 mg/l
      at trough and 5.03 to 25.91 mg/l at peak. The oral bioavailability,
      pharmacokinetic profile and antibacterial spectrum of linezolid make this
      oxazolidonone antimicrobial an attractive drug for the treatment of chronic
      osteomyelitis. Prolonged administration requires careful surveillance for side
      effects, until these complications are better understood.

PMID- 17024801
TI  - Linezolid as rescue drug: a clinical case of soft tissue infection caused by a
      Staphylococcus aureus strain resistant in vivo to teicoplanin.
AB  - The authors report and discuss a patient admitted to intensive care unit (ICU)
      for acute respiratory failure due to upper airway obstruction caused by face and
      neck soft tissue infection. An oxacillin-resistant Staphyloccoccus aureus was
      isolated from necrotic skin lesions and from skin biopsy. The strain was
      susceptible in vitro to teicoplanin, but it showed resistance in vivo, despite
      appropriate dosage. After 6 days of full dose therapy, since the clinical course
      worsened, teicoplanin was interrupted and linezolid was started. In 48 hours
      signs of infection regressed, and the patient was discharged from the ICU after
      10 days of linezolid treatment. Linezolid resulted as a rescue drug for a life
      threatening infection.

PMID- 17024802
TI  - Stage IB malignant thymoma in a Lynch syndrome patient with multiple cancers:
      response to incidental administration of oxaliplatin and 5-fluorouracil.
AB  - Chemotherapy is active against malignant thymomas, improving the resectability
      rate and the outcome of the advanced stages. The CAP and ADOC schemes are
      considered the standard schedules today, but these regimens can have important
      side effects in patients treated with combined approaches, such as toxic deaths
      due to congestive heart failure or hepatic insufficiency. We report the case of a
      55 year-old woman with a history of multiple neoplasms including a mixed
      malignant thymoma WHO type B2 and three synchronous adenocarcinomas of the colon.
      The patient refused to undergo surgical resection of her mediastinal mass.
      However, 8 cycles of chronomodulated oxaliplatin, 5-fluorouracil and leucovorin
      as adjuvant treatment for her colon cancers resulted in a > 30% decrease in the
      longest diameter of the mediastinal mass. This occasional observation may be
      important for clinicians and especially for those faced with relapsed, cisplatin
      refractory disease or when planning new studies aiming to reduce overall toxicity
      of multimodal schedules.

PMID- 17024803
TI  - Primary resistance and antibiotic minimum inhibitory concentrations for
      Helicobacter pylori strains, in Split, Croatia.

PMID- 17024804
TI  - Linezolid-resistant Enterococcus faecalis: first report in Spain.

PMID- 17024805
TI  - Melioidosis in an Italian tourist injured by the tsunami in Thailand.

PMID- 17024806
TI  - Successful treatment of an Aspergillus fumigatus Infection with voriconazole via
      a nasogastric tube.

PMID- 17024808
TI  - [Analysis of survival and annual mortality in malignant skin melanoma on the
      population level].

PMID- 17024807
TI  - [Oral and pharyngeal mucositis: pathogenesis, classification and means of
      correction].

PMID- 17024809
TI  - [Analysis of morbidity and the ratio of patients with malignant lymphomas in the
      Russian Federation].

PMID- 17024810
TI  - [Changes in copy number and deletion development of mitochondrial DNA in blood
      cells from breast cancer patients during radiochemotherapy].
AB  - Changes in mitochondrial DNA (mtDNA) copy number were compared versus the nuclear
      beta-globulin gene (internal standard), as well as occurrence of large mtDNA
      deletions in peripheral blood samples from 21 breast cancer patients following
      chemoradiotherapy. The study used polymerase chain reaction. Distinct variations
      were identified both in mtDNA copy number versus nuclear DNA and large mtDNA
      deletions occurrence in blood cells in response to genotoxic influence of
      chemoradiotherapy. Some mtDNA copies in breast cancer patients blood cells
      revealed large deletions whose frequency increased after chemoradiotherapy.
      Mitochondrial DNA lesions would induce synthesis of mtDNA copies in the course of
      chemoradiotherapy, which pointed to a compensatory reaction in peripheral blood
      cells as a consequence of a disturbed energy biogenesis.

PMID- 17024811
TI  - [Comparative assessment of the five-year results of surgical, combined, radiation
      and chemoradiotherapy in laryngeal cancer (T3N0M0)].
AB  - Four modalities of specific treatment for laryngeal cancer were compared in 158
      patients. Five-year survival after chemoradiotherapy using cisplatin, 5-FU and
      bleomycin plus irradiation (65-70 Gy) was 87% versus 69.7; 66.2 and 45.9% after
      surgical, combined and radiotherapy, respectively. Chemoradiotherapy failed in
      22.4%, as compared with 28.9; 31.5 and 41.7% after the alternative modalities,
      respectively. Organ preservation was used in 30.3% of surgical cases and 58%--in
      combined treatment group.

PMID- 17024812
TI  - [Diagnosis and treatment of lung cancer associated with paracancerous changes in
      the thoracic cavity].
AB  - Incidence of lung cancer associated with secondary paracancerous changes is known
      to range 13.7-30%. Since they reveal such clinical symptoms as pneumonia or
      empyema, most out-patients with complicated cancers are referred to general
      wards. Inflammatory parenchymal pathology may be conducive to false-positive or 
      negative diagnosis even when highly-sophisticated radiation procedures are used.

PMID- 17024813
TI  - [Postoperative features in lung cancer patients receiving intraoperative
      radiotherapy and radiosensitization].
AB  - Research Institute of Oncology, Research Center, Russian Academy of Medical
      Sciences, Siberian Branch, Tomsk. Postoperative course was studied of stage III
      non-small cell lung cancer (35) treated radically using intraoperative
      radiotherapy (15Gy) and cisplatin radiosensitization. Postoperative complications
      were reported in 11.4 +/- 5.4%. Reduction in complication rates was due to the
      use of a combined treatment complex. There were no postoperative lethalities.

PMID- 17024814
TI  - [Modulating effect of antileukemia drugs on the cellular susceptibility in
      chronic myeloid leukemia to cytotoxic lymphocytes].
AB  - A 24-hour pre-treatment of leukemic K-562 cells with busulfan or N
      hydroxycarbamide (rather than cytarabine) lowered their resistance to the toxic
      effect of peripheral blood mononuclear cells. Non-linear modulating influence was
      registered even at low dosage of cytostatics which actually could not affect
      leukemic cell viability.

PMID- 17024815
TI  - [Molecular biology investigation of respiratory viruses as a factor of infectious
      complications in hemoblastosis and myelodepression].
AB  - Communicable respiratory viruses as a causative factor of infectious complication
      in hemoblastosis and myelodepression were investigated in 51 patients (aplastic
      anemia--3, multiple myeloma--10, different patterns of acute leukemia--16,
      chronic leukemia--8 and non-Hodgkin's lymphoma--14). Our clinical evidence
      obtained with the aid of polymerase chain reaction featured genomes of
      adenoviruses, influenza A and B viruses, respiratory-scintillating virus and
      coronaviruses. On the whole, respiratory viral infections were detected in 27
      (52.9%) patients: adenoviruses--23.5%, coronaviruses--13.7%, influenza A and B-
      5.9% and respiratory-scintillating virus--3.9%. In many cases, herpes was
      associated with viral respiratory infection. That pathology was most often
      triggered by severe neutropenia induced by chemotherapy.

PMID- 17024816
TI  - [Carcinogenic components of smokeless tobacco and tobacco-free cigarettes].
AB  - The investigation deals with an assessment of carcinogenicity and mutagenicity of
      samples of smokeless tobacco now on the Russian market as well as ash from
      alternative cigarettes made of aromatic herbs. Our data showed that the levels of
      polycyclic aromatic hydrocarbons, volatile and tobacco-specific N-nitrosoamines
      complied with the standards in the producer-countries. Smokeless tobacco extracts
      failed to show (Ames) any mutagenic effects such as the "read-out frame shift" or
      "base-pair replacement" patterns. No tobacco-specific N-nitrosoamines were
      identified in herbal cigarettes. However, polycyclic aromatic hydrocarbons and
      volatile N-nitrosoamines content appeared to be identical to that of tobacco.
      Herbal cigarette smoke extracts mutagenicity induced by side-effects of
      carcinogenic substances was of similar magnitude as well.

PMID- 17024817
TI  - [The role of gap junction communication in metastatic B16 melanoma in C57BL
      mice].
AB  - The study is concerned with the effects of non-specific blocking gap junction
      communication with oleamide as well as genesis and spreading of melanoma B16
      metastases to the lung in mice C57B1. The blocking exerted no distinct influence
      on primary tumorigenesis but had a marked effect on metastatic spread. Oleamide
      treatment during tumor growth led to an increase in area covered by metastases. A
      correlation was established between metastatic frequency and dosage: 1 mg/kg was
      followed by an upsurge in frequency of secondary lung tumors while 10 mg/kg--by a
      drop.

PMID- 17024818
TI  - [Treatment of cancer metastasis in the brain].
AB  - Surgery for brain metastases is an effective treatment for most cancer patients.
      It involves low post-operative lethality (2.9%) and causes neurological symptoms
      to regress in most patients. 12-month survival occured in 48.5%, 5 years--10.8%;
      mean survival duration with good quality of life--11.8 months. Survival basically
      depended on tumor pattern, metastases to other organs, multiple foci in the brain
      and habitus.

PMID- 17024819
TI  - [Potential of optical coherence tomography for diagnosing mucositis in cancer of
      the nasal cavity and throat in the course of radio- and chemoradiotherapy].
AB  - The monitoring data on mucosa of the nasal cavity and throat using optical
      coherence tomography imaging in 14 cases during radiochemotherapy are presented.
      Typical alterations such as reduction in contrast distinctions between tissue
      layers to an extent that it blurs down completely at the peak of radiation
      related response are discussed. Due to use of the technique valuable information
      on individual response was obtained.

PMID- 17024820
TI  - [Preoperative radiotherapy and extended surgical procedures for stomach cancer-
      assessment of safety of the combined approach].
AB  - Immediate results of D-2 surgery for stomach cancer are presented. No
      significanty was reported during combination therapy including preoperative
      gammatherapy 2) a rise in complication incidence or lethality. Hence, D-2 surgery
      is a safe antitumor procedure.

PMID- 17024821
TI  - [Treatment results in endometrial cancer in patients of reproductive age].
AB  - 195 reproductive patients (23-29 years--6.2%, 40-45 years--57.4%) were treated
      for endometrial carcinoma. Stage I was detected in 64.4%, II--14.9%, III--8.7%
      and IV--3.1%. Well-differentiated cell adenocarcinoma was 3.1 times as frequent
      as light-cell, seroso-papillary, moderately-, low- and undifferentiated
      adenocarcinoma characterized by unfavorable clinical course. Overall 5-year
      survival was 89.8% (stage I--94.8%, II--78.6%, III-IV--69.7%).

PMID- 17024822
TI  - [Changes of urinary enzyme activity in cancer of the urinary bladder].
AB  - Assays of blood serum and urine samples from patients with cancer of the urinary
      bladder established enhanced levels of lactate dehydrogenase (LDH). The findings
      were significant as far as malignancies were concerned. Male patients with
      transitional cell carcinoma revealed significant increase in DH blood serum
      while, in moderately- and low-differentiated tumor cases, it was higher in urine.
      In female patients, increased levels were registered in urine and in low
      differentiated tumor only. Prognostic value of LDH levels in males was relatively
      higher.

PMID- 17024823
TI  - [Correlation of the frequency of surgical procedures on the peripheral
      immunologic organs with the frequency of oncologic and other somatic diseases].
AB  - Regional Oncological Dispensary, Kostroma The study included 388 cancer patients
      (group 1) and 381 cases of other pathologies (group 2). Surgery on lymphoid
      organs was performed in 121 patients (31%) in group 1 and 150 in group 2. It was
      concluded that such intervention in the immune system was not an oncological
      hazard. That phenomenon might be accounted for by the specificity of immune
      response in patients suffering from such diseases.

PMID- 17024824
TI  - [The use of gemcitabine in the treatment of patients with mesothelioma].

PMID- 17024825
TI  - [Incidence of Helicobacter pylori infection in stomach cancer patients].

PMID- 17024826
TI  - [Palliative therapy of advanced cancer of the lung].

PMID- 17024827
TI  - [The enigma of desmoid fibroma].

PMID- 17024828
TI  - [The history of prophylactic cytological screening for carcinoma and precancerous
      conditions of the uterine cervix in Russia].

PMID- 17024829
TI  - Characterizing the shape of anatomical structures with Poisson's equation.
AB  - Poisson's equation, a fundamental partial differential equation in classical
      physics, has a number of properties that are interesting for shape analysis. In
      particular, the equipotential sets of the solution graph become smoother as the
      potential increases. We use the displacement map, the length of the streamlines
      formed by the gradient field of the solution, to measure the "complexity" (or
      smoothness) of the equipotential sets, and study its behavior as the potential
      increases. We believe that this function complexity = f(potential), which we call
      the shape characteristic, is a very natural way to express shape. Robust
      algorithms are presented to compute the solution to Poisson's equation, the
      displacement map, and the shape characteristic. We first illustrate our technique
      on two-dimensional synthetic examples and natural silhouettes. We then perform
      two shape analysis studies on three-dimensional neuroanatomical data extracted
      from magnetic resonance (MR) images of the brain. In the first study, we
      investigate changes in the caudate nucleus in Schizotypal Personality Disorder
      (SPD) and confirm previously published results on this structure. In the second
      study, we present a data set of caudate nuclei of premature infants with
      asymmetric white matter injury. Our method shows structural shape differences
      that volumetric measurements were unable to detect.

PMID- 17024830
TI  - Spherical harmonics microwave algorithm for shape and location reconstruction of
      breast cancer tumor.
AB  - A reconstruction algorithm to simultaneously estimate the shape and location of
      three-dimensional breast cancer tumor is presented and its utility is analyzed.
      The approach is based on a spherical harmonic decomposition to capture the shape
      of the tumor. We combine a gradient descent optimization method with a direct
      electromagnetic solver to determine the coefficients in the harmonic expansion as
      well as the coordinates of the center of the tumor. The results demonstrate the
      potential advantage of collecting data using a multiple-view/tomographic-type
      strategy. We show how the order of the harmonic expansion must be increased to
      capture increasingly "irregularly" shaped tumors and explore the resulting
      increase in the central processing unit (CPU) time required by the algorithm. Our
      approach shows accurate reconstruction of the tumor image regardless of the
      source polarization. This work demonstrates the promise of the algorithm when
      used on data corrupted with Gaussian noise and when perfect knowledge of the
      tumor electrical properties is not available.

PMID- 17024831
TI  - Penalized weighted least-squares approach to sinogram noise reduction and image
      reconstruction for low-dose X-ray computed tomography.
AB  - Reconstructing low-dose X-ray computed tomography (CT) images is a noise problem.
      This work investigated a penalized weighted least-squares (PWLS) approach to
      address this problem in two dimensions, where the WLS considers first- and second
      order noise moments and the penalty models signal spatial correlations. Three
      different implementations were studied for the PWLS minimization. One utilizes a
      Markov random field (MRF) Gibbs functional to consider spatial correlations among
      nearby detector bins and projection views in sinogram space and minimizes the
      PWLS cost function by iterative Gauss-Seidel algorithm. Another employs Karhunen
      Loeve (KL) transform to de-correlate data signals among nearby views and
      minimizes the PWLS adaptively to each KL component by analytical calculation,
      where the spatial correlation among nearby bins is modeled by the same Gibbs
      functional. The third one models the spatial correlations among image pixels in
      image domain also by a MRF Gibbs functional and minimizes the PWLS by iterative
      successive over-relaxation algorithm. In these three implementations, a quadratic
      functional regularization was chosen for the MRF model. Phantom experiments
      showed a comparable performance of these three PWLS-based methods in terms of
      suppressing noise-induced streak artifacts and preserving resolution in the
      reconstructed images. Computer simulations concurred with the phantom experiments
      in terms of noise-resolution tradeoff and detectability in low contrast
      environment. The KL-PWLS implementation may have the advantage in terms of
      computation for high-resolution dynamic low-dose CT imaging.

PMID- 17024832
TI  - Multifrequency vibro-acoustography.
AB  - Elasticity imaging is a burgeoning medical imaging field. Many methods have been
      proposed that impart a force to tissue and measure the mechanical response. One
      method, vibro-acoustography, uses the ultrasound radiation force to harmonically
      vibrate tissue and measure the resulting acoustic emission field with a nearby
      hydrophone. Another method, vibrometry, uses the ultrasound radiation force
      accompanied with a measurement of the resulting velocity or displacement of the
      vibrating tissue or object has also been used for different applications. An
      extension of the vibro-acoustography method using a multifrequency stress field
      to vibrate an object is described. The objective of this paper is to present the
      image formation theory for multifrequency vibro-acoustography. We show that the
      number of low-frequency components created by this multifrequency method scales
      with the square of the number of ultrasound sources used. We provide experimental
      validation of the point-spread function of the multifrequency stress field and
      show examples of both vibrometry and vibro-acoustography imaging applications.
      This method holds the potential for a large gain of information with no increase
      in scanning time compared to conventional vibro-acoustography systems.

PMID- 17024833
TI  - Smooth functional and structural maps on the neocortex via orthonormal bases of
      the Laplace-Beltrami operator.
AB  - Functional and structural maps, such as a curvature, cortical thickness, and
      functional magnetic resonance imaging (MRI) maps, indexed over the local
      coordinates of the cortical manifold play an important role in neuropsychiatric
      studies. Due to the highly convoluted nature of the cerebral cortex and image
      quality, these functions are generally uninterpretable without proper methods of
      association and smoothness onto the local coordinate system. In this paper, we
      generalized the spline smoothing problem (Wahba, 1990) from a sphere to any
      arbitrary two-dimensional (2-D) manifold with boundaries. We first seek a
      numerical solution to orthonormal basis functions of the Laplace-Beltrami (LB)
      operator with Neumann boundary conditions for a 2-D manifold M then solve the
      spline smoothing problem in a reproducing kernel Hilbert space (r.k.h.s.) of real
      valued functions on manifold M with kernel constructed from the basis functions.
      The explicit discrete LB representation is derived using the finite element
      method calculated directly on the manifold coordinates so that finding discrete
      LB orthonormal basis functions is equivalent to solving an algebraic eigenvalue
      problem. And then smoothed functions in r.k.h.s can be represented as a linear
      combination of the basis functions. We demonstrate numerical solutions of
      spherical harmonics on a unit sphere and brain orthonormal basis functions on a
      planum temporale manifold. Then synthetic data is used to quantify the goodness
      of the smoothness compared with the ground truth and discuss how many basis
      functions should be incorporated in the smoothing. We present applications of our
      approach to smoothing sulcal mean curvature, cortical thickness, and functional
      statistical maps on submanifolds of the neocortex.

PMID- 17024834
TI  - Noninvasive reconstruction of three-dimensional ventricular activation sequence
      from the inverse solution of distributed equivalent current density.
AB  - We propose a new electrocardiographic (ECG) inverse approach for imaging the
      three-dimensional (3-D) ventricular activation sequence based on the modeling and
      estimation of the equivalent current density throughout the entire volume of the
      ventricular myocardium. The spatio-temporal coherence of the ventricular
      excitation process has been utilized to derive the activation time from the
      estimated time course of the equivalent current density. In the present study, we
      explored four different linear inverse algorithms (the minimum norm and weighted
      minimum norm estimates in combination with two regularization schemes: the
      instant-by-instant regularization and the isotropy method) to estimate the
      current density at each time instant during the ventricular depolarization. The
      activation time at any given location within the ventricular myocardium was
      determined as the time point with the occurrence of the maximum local current
      density estimate. Computer simulations were performed to evaluate this approach
      using single- and dual-site pacing protocols in a physiologically realistic
      cellular automaton heart model. The performance and stability of the proposed
      approach was evaluated with respect to the various levels of measurement noise
      (0, 5, 10, 20, 40, and 60 microV), the various numbers of ECG electrodes and the
      modeling errors on the torso geometry and heart position. The simulation results
      demonstrate that: 1) the single-site paced 3-D activation sequence can be well
      reconstructed from 200-channel body surface potential maps with additive Gaussian
      white noise of 20 microV (correlation coefficient = 0.90, relative error = 0.19,
      and localization error = 5.49 mm); 2) a higher imaging accuracy can be obtained
      when the activation is initiated from the left/right ventricle (LV/RV) compared
      to from the septum; 3) the isotropy method gives rise to a better performance
      than the conventional instant-by-instant regularization; 4) a decreased imaging
      accuracy results from a larger noise level, a fewer number of electrodes, or the
      volume conductor modeling errors; however, a reasonable imaging accuracy can
      still be obtained with a 60 microV noise level, 64 electrodes, or mild errors on
      both the torso geometry and heart position, respectively; 5) the dual-site paced
      3-D activation sequence can be imaged when the two sites are paced either
      simultaneously or with a time delay of 20 ms; 6) two pacing sites can be resolved
      and localized in the imaged 3-D activation sequence when they are located at the
      contralateral sides of ventricles or at the ventricular lateral wall and the
      apex, respectively.

PMID- 17024835
TI  - Blockwise processing applied to brain microvascular network study.
AB  - The study of cerebral microvascular networks requires high-resolution images.
      However, to obtain statistically relevant results, a large area of the brain
      (several square millimeters) must be analyzed. This leads us to consider huge
      images, too large to be loaded and processed at once in the memory of a standard
      computer. To consider a large area, a compact representation of the vessels is
      required. The medial axis is the preferred tool for this application. To extract
      it, a dedicated skeletonization algorithm is proposed. Numerous approaches
      already exist which focus on computational efficiency. However, they all
      implicitly assume that the image can be completely processed in the computer
      memory, which is not realistic with the large images considered here. We present
      in this paper a skeletonization algorithm that processes data locally (in
      subimages) while preserving global properties (i.e., homotopy). We then show some
      results obtained on a mosaic of three-dimensional images acquired by confocal
      microscopy.

PMID- 17024836
TI  - Prostate mechanical imaging: 3-D image composition and feature calculations.
AB  - We have developed a method and a device entitled prostate mechanical imager (PMI)
      for the real-time imaging of prostate using a transrectal probe equipped with a
      pressure sensor array and position tracking sensor. PMI operation is based on
      measurement of the stress pattern on the rectal wall when the probe is pressed
      against the prostate. Temporal and spatial changes in the stress pattern provide
      information on the elastic structure of the gland and allow two-dimensional (2-D)
      and three-dimensional (3-D) reconstruction of prostate anatomy and assessment of
      prostate mechanical properties. The data acquired allow the calculation of
      prostate features such as size, shape, nodularity, consistency/hardness, and
      mobility. The PMI prototype has been validated in laboratory experiments on
      prostate phantoms and in a clinical study. The results obtained on model systems
      and in vivo images from patients prove that PMI has potential to become a
      diagnostic tool that could largely supplant DRE through its higher sensitivity,
      quantitative record storage, ease-of-use and inherent low cost.

PMID- 17024837
TI  - Ultrahigh-field MRI whole-slice and localized RF field excitations using the same
      RF transmit array.
AB  - In this paper, a multiport driving mechanism is numerically implemented at ultra
      high-field (UHF) magnetic resonance imaging (MRI) to provide 1) homogenous whole
      slice (axial, sagittal, or coronal) and 2) highly localized radio frequency (RF)
      field excitation within the same slices, all with the same RF transmit array
      (here chosen to be a standard transverse electromagnetic (TEM) resonator/coil).
      The method is numerically tested using a full-wave model of a TEM coil loaded
      with a high-resolution/18-tissue/anatomically detailed human head mesh. The
      proposed approach is solely based on electromagnetic and phased array antenna
      theories. The results demonstrate that both homogenous whole-slice as well as
      localized RF excitation can be achieved within any slice of the head at 7 T (298
      MHz for proton imaging).

PMID- 17024838
TI  - The effect of nonlinear human visual system components on performance of a
      channelized Hotelling observer in structured backgrounds.
AB  - Linear model observers based on statistical decision theory have been used
      successfully to predict human visual detection of aperiodic signals in a variety
      of noisy backgrounds. However, some models have included nonlinearities such as a
      transducer or nonlinear decision rules to handle intrinsic uncertainty. In
      addition, masking models used to predict human visual detection of signals
      superimposed on one of two identical backgrounds (masks) usually include a number
      of nonlinear components in the channels that reflect properties of the firing of
      cells in the primary visual cortex (V1). The effect of these nonlinearities on
      the ability of linear model observers to predict human signal detection in real
      patient structured backgrounds is unknown. We evaluate the effect of including
      different nonlinear human visual system components into a linear channelized
      Hotelling observer (CHO) using a signal known exactly but variable (SKEV) task.
      In particular, we evaluate whether the rank order of two compression algorithms
      (JPEG versus JPEG 2000) and two compression encoder settings (JPEG 2000 default
      versus JPEG 2000 optimized) based on model observer signal detection performance
      in X-ray coronary angiograms is altered by inclusion of nonlinear components. The
      results show: 1) the simpler linear CHO model observer outperforms CHO model with
      the nonlinear components; 2) the rank order of model observer performance for the
      compression algorithms/parameters does not change when the nonlinear components
      are included. For the present task and images, the results suggest that the
      addition of the nonlinearities to a channelized Hotelling model may add
      complexity to the model observers without great impact on rank order evaluation
      of image processing and/or acquisition algorithms.

PMID- 17024839
TI  - Analytical calculation of volumes-of-intersection for iterative, fully 3-D PET
      reconstruction.
AB  - Use of iterative algorithms to reconstruct three-dimensional (3-D) positron
      emission tomography (PET) data requires the computation of the system probability
      matrix. The pure geometrical contribution can easily be approximated by the
      length-of-intersection (LOI) between lines-of-response (LOR) and individual
      voxels. However, more accurate geometrical projectors are desirable. Therefore,
      we have developed a fast method for the analytical calculation of the 3-D shape
      and volume of volumes-of-intersection (VOI). This method provides an alternative
      robust projector with a uniformly continuous sampling of the image space. The
      enhanced calculation effort is facilitated by using several speedup techniques.
      Exploiting intrinsic symmetry relations and the sparseness of the system matrix
      allows to create an efficiently compressed matrix which can be precomputed and
      completely stored in memory. In addition, a new voxel addressing scheme has been
      implemented. This scheme avoids time-consuming symmetry transformations of voxel
      addresses by using an octant-wise symmetrically ordered field of voxels. The
      above methods have been applied for a fully 3-D, iterative reconstruction of 3-D
      sinograms recorded with a Siemens/CTI ECAT HR+ PET scanner. A comparison of the
      performance of the reconstruction using LOI weighting and VOI weighting is
      presented.

PMID- 17024840
TI  - Robust online orientation correction for radiographs in PACS environments.
AB  - In picture archiving and communications systems (PACS), images need to be
      displayed in standardized ways for radiologists' interpretations. However, for
      most radiographs acquired via computed radiography (CR), digital radiography
      (DR), or digitized films, the image orientation is undetermined because of the
      variations in examination conditions and patients' situations. To address this
      problem, an automatic orientation correction method is developed. It first
      detects the most indicative region in a radiograph for image orientation, and
      then extracts a set of low-level visual features from the region. Based on these
      features, a well-trained classifier, using support vector machines, is employed
      to recognize the correct orientation of the radiograph and reorient it to the
      desired position. A large-scale experiment was conducted on more than 12 000
      radiographs, which covered a wide variety of exam types, to validate the method.
      The overall success rate of orientation correction was 96.1%. A workflow study on
      the method also demonstrated a significant improvement in efficiency for image
      display. To our knowledge, this work represents the first robust system designed
      to handle all radiographic exam types using a unified framework instead of using
      dedicated strategies for different exam types.

PMID- 17024841
TI  - Variational Bayes inference of spatial mixture models for segmentation.
AB  - Mixture models are commonly used in the statistical segmentation of images. For
      example, they can be used for the segmentation of structural medical images into
      different matter types, or of statistical parametric maps into activating and
      nonactivating brain regions in functional imaging. Spatial mixture models have
      been developed to augment histogram information with spatial regularization using
      Markov random fields (MRFs). In previous work, an approximate model was developed
      to allow adaptive determination of the parameter controlling the strength of
      spatial regularization. Inference was performed using Markov Chain Monte Carlo
      (MCMC) sampling. However, this approach is prohibitively slow for large datasets.
      In this work, a more efficient inference approach is presented. This combines a
      variational Bayes approximation with a second-order Taylor expansion of the
      components of the posterior distribution, which would otherwise be intractable to
      Variational Bayes. This provides inference on fully adaptive spatial mixture
      models an order of magnitude faster than MCMC. We examine the behavior of this
      approach when applied to artificial data with different spatial characteristics,
      and to functional magnetic resonance imaging statistical parametric maps.

PMID- 17024842
TI  - Pose estimation of known objects during transmission tomographic image
      reconstruction.
AB  - We address the problem of image formation in transmission tomography when metal
      objects of known composition and shape, but unknown pose, are present in the scan
      subject. Using an alternating minimization (AM) algorithm, derived from a model
      in which the detected data are viewed as Poisson-distributed photon counts, we
      seek to eliminate the streaking artifacts commonly seen in filtered back
      projection images containing high-contrast objects. We show that this algorithm,
      which minimizes the I-divergence (or equivalently, maximizes the log-likelihood)
      between the measured data and model-based estimates of the means of the data,
      converges much faster when knowledge of the high-density materials (such as
      brachytherapy applicators or prosthetic implants) is exploited. The algorithm
      incorporates a steepest descent-based method to find the position and orientation
      (collectively called the pose) of the known objects. This pose is then used to
      constrain the image pixels to their known attenuation values, or, for example, to
      form a mask on the "missing" projection data in the shadow of the objects.
      Results from two-dimensional simulations are shown in this paper. The extension
      of the model and methods used to three dimensions is outlined.

PMID- 17024843
TI  - Evaluation of anticancer activity of 4-vinyl-1-arylsulfonylimidazolidinones.
AB  - To continue exploration of structure activity relationship of novel 1-(indoline-5
      sulfonyl)-4-phenylimidazolidinones (1) reported as anticancer agent with broad
      spectrum, three 1-(arylsulfonyl)-4-vinylimidazolidinones (2) were synthesized
      from methyl serinate (3) in 8 steps. Reaction of intermediate 2
      phenoxycarbonylaminobut-3-enyl p-toluenesulfonate (10) with arylsulfonamide in
      the presence of potassium carbonate produced corresponding 2 and N-(4
      vinyloxazolidin-2-yl)arylsulfonamide 11 in approximately equal ratio. This
      reaction is believed to undergo through urea intermediate 16 as shown in scheme
      3. 1-Arylsufonyl-4-vinylimidazolidinones 2 show much reduced activity against
      human colon carcinoma (Colo205), human chronic myelogenous leukemia (K562), and
      human ovarian adenocarcinoma (SK-OV-3) and compatible activity against human lung
      carcinoma (A549) compared to 1. Therefore phenyl at 4-position should be the
      optimum planar motif for the activity of 1.

PMID- 17024844
TI  - Synthesis of 7-hydroxy-4-oxo-4H-chromene- and 7-hydroxychroman-2-carboxylic acid
      N-alkyl amides and their antioxidant activities.
AB  - A series of 7-hydroxy-4-oxo-4H-chromene- (3a - h) and 7-hydroxychroman-2
      carboxylic acid N-alkyl amides (4a - g) were synthesized and their antioxidant
      activities were evaluated. While compounds 3a - h were less active, compounds 4a 
      g exhibited more potent inhibition of lipid peroxidation initiated by Fe2+ and
      ascorbic acid in rat brain homogenates. Among them, 7-hydroxychroman-2-carboxylic
      acid N-alkylamides (4e - g) bearing nonyl, decyl, and undecyl side chain
      exhibited 3 times more potent inhibition than trolox (1).

PMID- 17024845
TI  - Effect of ginseng polysaccharide on the stability of lactic acid bacteria during
      freeze-drying process and storage.
AB  - Lactic acid bacteria (LAB) quickly attenuate or are killed during the freeze
      drying process and storage. The effect of some natural polysaccharides, which are
      known as potent antitumor and immunomodulating substances, on the viability of
      the LAB, Lactobacillus acidophilus and Bifidobacterium breve, on freeze-drying
      and storage were investigated. Among the polysaccharides tested, red ginseng
      polysaccharide (RGP) and chitosan significantly inhibited the cell death of the
      LAB during freeze-drying, and fucoidan and RGP most potently protected the cell
      death of the LAB during storage. The stabilities of the LAB on the addition of
      RGP and fucoidan were comparable to that of skimmed milk. However, white ginseng
      polysaccharide (WGP) did not promote storage stability. When 5% skimmed milk/5%
      RGP treated LAB were freeze-dried and stored, their viabilities were found to be
      significantly higher those treated with 5% or 10% RGP. The stabilizing effect of
      5% RGP/5% skimmed milk during LAB freeze-drying and storage stability was
      comparable to that of treatment with 10% skimmed milk. Based on these findings,
      we believe that RGP beneficially improves the stability of LAB during the freeze
      dry process and storage.

PMID- 17024846
TI  - Estrogenic activity of furanocoumarins isolated from Angelica dahurica.
AB  - In our efforts to discover novel phytoestrogens to treat menopausal symptoms,
      eleven furanocoumarins were isolated from Angelica dahurica and tested for their
      estrogenic activity on the Ishikawa cell line. Among the compounds tested, 9
      hydroxy-4-methoxypsoralen and alloisoimperatorin showed strong abilities to
      induce alkaline phosphatase (AP) with EC50 values of 1.1 and 0.8 microg/mL,
      respectively, whereas the other nine furanocoumarins were weakly or only slightly
      active.

PMID- 17024847
TI  - Antifungal effect of amentoflavone derived from Selaginella tamariscina.
AB  - Amentoflavone is a plant bif avonoid that was isolated from an ethyl acetate
      extract of the whole plant of Selaginella tamariscina (Beauv.) spring. 1D and 2D
      NMR spectroscopy including DEPT, HMQC, and HMBC were used to determine its
      structure. Amentoflavone exhibited potent antifungal activity against several
      pathogenic fungal strains but had a very low hemolytic effect on human
      erythrocytes. In particular, amentoflavone induced the accumulation of
      intracellular trehalose on C. albicans as a stress response to the drug, and
      disrupted the dimorphic transition that forms pseudo-hyphae during pathogenesis.
      In conclusion, amentoflavone has great potential to be a lead compound for the
      development of antifungal agents.

PMID- 17024848
TI  - Lactic acid bacteria increase antiallergic effect of Artemisia princeps pampanini
      SS-1.
AB  - Artemisia princeps Pampanini, which is called Ssajuarissuk in Korean (SS-1), was
      fermented with lactic acid bacteria (LAB) and their passive cutaneous anaphylaxis
      reaction-inhibitory activity was investigated. Of these fermented agents, SS-1
      extract fermented with Bifidobacterium infantis K-525 (F-SS-1) most effectively
      inhibited the release of P-hexosamindase from RBL-2H3 cells induced IgE. In IgE
      induced RBL-2H3 cells, F-SS-1 inhibited proinflammatory cytokines IL-6 and TNF
      alpha mRNA expression. Oral administration of SS-1 and F-SS-1 to mice inhibited
      passive cutaneous anaphylaxis (PCA) reaction induced by IgE and scratching
      behaviors induced by compound 48/80. The inhibitory activity of F-SS-1 against
      scratching behaviors was more effective than that of SS-1. These findings suggest
      that the fermentation of SS-1 with LAB can increase its antiallergic activity.

PMID- 17024849
TI  - Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug
      resistance (MDR) from the rhizome of Coptis japonica Makino.
AB  - Six protoberberine alkaloids were isolated from the chloroform layer of the
      rhizome of Coptis japonica Makino (Ranunculaceae). The structures of the isolated
      compounds were determined to be 6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)
      2,3-dimethoxy-benzoic acid methyl ester (1), oxyberberine (2), 8-oxo-epiberberine
      (3), 8-oxocoptisine (4), berberine (5) and palmatine (6) by physicochemical and
      spectroscopic methods. The compound 3 (8-oxo-epiberberine) was first isolated
      from natural sources. The compounds were tested for cytotoxicity against five
      tumor cell lines in vitro by SRB method, and also tested for the MDR reversal
      activities. Compound 4 was of significant P-gp MDR inhibition activity with ED50
      value 0.018 microg/mL in MES-SA/DX5 cell and 0.0005 microg/mL in HCT15 cell,
      respectively.

PMID- 17024850
TI  - Natural compounds from Danshen suppress the activity of hepatic stellate cells.
AB  - Danshen is an herbal medication frequently used in oriental medicine to treat
      liver or kidney malfunction. In the course of our studies, we observed that
      compounds purified from Danshen exhibit an inhibitory activity against Discoidin
      Domain Receptor 2 (DDR2) tyrosine kinase. Through this inhibition, these
      compounds also inhibited the growth of HSC T6 cells and suppressed the expression
      of alpha-smooth muscle actin and MMP2, as well as collagen synthesis, all of
      which are increased in activated liver stellate cells. Given that activation of
      liver stellate cells is the hallmark of liver fibrosis and that DDR2 plays a
      critical role in this activation, these results suggest that one of the
      pharmacological activities of Danshen extract that protects the liver is the
      inhibition of key cell-signaling kinases, such as DDR2, in liver stellate cells.

PMID- 17024851
TI  - Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob
      mice.
AB  - Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight
      reduction alone does not prevent the progression of NAFLD to end-stage disease
      associated with the development of cirrhosis and liver disease. In a previous
      experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was
      found to reduce body weight and insulin resistance in high fat diet-induced
      hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action
      of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB
      ethanol extract for an 8 week-period. ASSB ethanol extract reversed the
      hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB
      ethanol extract also specifically lowered circulating glucose and lipids, and
      enhanced insulin action in the liver. These changes culminated in inhibition of
      triglyceride synthesis in non-adipose tissues including liver and skeletal
      muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and
      lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol
      extract is an effective treatment for insulin resistance and hepatic steatosis in
      ob/ob mice by decreasing hepatic lipid synthesis.

PMID- 17024852
TI  - Effects of Nelumbinis Semen on contractile dysfunction in ischemic and reperfused
      rat heart.
AB  - Nelumbinis Semen (NS), or lotus seed, is one of the most well-known traditional
      herbal medicines and is frequently used to treat cardiovascular symptoms in
      Korea. The anti-ischemic effects of NS on ischemia-induced isolated rat heart
      were investigated through analyses of changes in blood pressure, aortic flow,
      coronary flow, and cardiac output. The subjects in this study were divided into
      two groups: a control, untreated ischemia-induced group, and an ischemia-induced
      group treated with NS. There were no significant differences in perfusion
      pressure, aortic flow, coronary flow and cardiac output between the groups before
      ischemia was induced. The supply of oxygen and buffer was stopped for ten minutes
      to induce ischemia in isolated rat hearts, and NS was administered during
      ischemia induction. NS treatment significantly prevented decreases in perfusion
      pressure, aortic flow, coronary flow and cardiac output under ischemic conditions
      (p < 0.01). In addition, the mechanism of the anti-ischemic effects of NS was
      also examined through quantitation of intracellular calcium content in rat
      neonatal cardiomyocytes. NS significantly prevented intracellular calcium
      increases induced by isoproterenol (p < 0.01). These results suggest that NS has
      distinct anti-ischemic effects through calcium antagonism.

PMID- 17024853
TI  - Glucose-lowering effect of powder formulation of African black tea extract in KK
      A(y)/TaJcl diabetic mouse.
AB  - We observed the suppressive effect of a powder formulation of African black tea
      extract prepared from the leaves of Camellia sinensis on type 2 non-insulin
      dependent diabetic mice, KK-A(y)/TaJcl. Black tea extract significantly showed
      suppressive effect of the elevation of blood glucose on oral glucose tolerance
      test of 8 week-old KK-A(y)/TaJcl mice (P < 0.05). Long-term treatment with black
      tea extract showed significant suppression of post-prandial blood glucose and
      obesity (P < 0.05). The weight of the intestine of mice treated with black tea
      extract was significantly reduced (P < 0.05). From these results, African black
      tea used in this study showed a suppressive effect on the elevation of blood
      glucose during food intake and the body weight.

PMID- 17024854
TI  - Research on thymopentin loaded oral N-trimethyl chitosan nanoparticles.
AB  - Peptides, although high efficacy and specificity in their physiological function,
      usually have low therapeutical activities due to their poor bioavailability when
      administrated orally. Nanoparticles have been regarded as a useful vector for
      targeted drug delivery system because they can protect drug from being degraded
      quickly and pass the gastrointestinal barriers. Here we described a novel oral N
      trimethyl chitosan nanoparticles formulation containing thymopentin (Tp5-TMC-NP).
      N-trimethyl chitosan (TMC) was synthesized and then used to prepare Tp5-TMC-NP by
      ionotropic gelation. A three-factor, five-level CCD (Central Composite Design)
      design was used in the optimization procedure, with HPLC as the analyzing method.
      The resulting Tp5-TMC-NP had a regular spherical surface and a narrow particle
      size range with a mean diameter of 110.6 nm. The average entrapment efficiency
      was 78.8%. The lyophilized Tp5-TMC-NP formulation was stable in 4 degrees C or 
      20 degrees C after storage of 3 months without obvious changes in morphology,
      particle size, pH and entrapment ratio. The results of the flow cytometer
      determination showed that the ratio of CD4+/CD8+ of Wistar female rat givenTp5
      TMC-NP (ig) was 2.59 time that of the group given Tp5 (ig).

PMID- 17024855
TI  - The therapeutic effect of tissue cultured root of wild Panax ginseng C.A. Mayer
      on spermatogenetic disorder.
AB  - This study examined the possibility of using a tissue cultured root of wild Panax
      ginseng (tcwPG) as a fertility agent. The effect of tcwPG on spermatogenesis was
      studied using male rats. The tcwPG crude powder was administered orally to 7-week
      old rats over a 6-week period. The number of sperm in the testes and epididymides
      was significantly higher than the control. A histological examination did not
      reveal any morphological changes in the testes from the tcwPG powder treated
      rats. Moreover, there were no significant differences in the weights of the
      heart, spleen, liver, kidney, brain, testes and epididymides. Oligospermia was
      also induced by administering 2,3,7,8-tetrachlorodaibenzo-p-dioxin (TCDD) to the
      rats in order to estimate the feasibility of using tcwPG as treatment for
      infertility caused by spermatogenic disorders. After exposing the rats to TCDD,
      the tcwPG saponin fraction treated rats showed some improvement in the body
      weight, sperm number and testis morphology. It was estimated that tcwPG had
      feasibility as a therapeutic agent on spermatogenic disorder.

PMID- 17024856
TI  - Chiral purity test of bevantolol by capillaryelectrophoresis and high performance
      liquid chromatography.
AB  - Two methods for the chiral purity determination of bevantolol were developed,
      namely capillary electrophoresis (CE) using carboxymethyl-beta-cyclodextrin (CM
      beta-CD) as a chiral selector and high-performance liquid chromatography (HPLC)
      using a chiral stationary phase. In the HPLC method, the separation of bevantolol
      enantiomers was performed on a Chiralpak AD-H column by isocratic elution with n
      hexane-ethanol-diethylamine (10:90:0.1, v/v/v) as mobile phase. In the CE method,
      bevantolol enantiomers were separated on an uncoated fused silica capillary with
      50 mM amonium phosphate dibasic adjusted to a pH 6.5 with phosphoric acid
      containing 15 mM CM-beta-CD as running buffer. Validation data such as linearity,
      recovery, detection limit, and precision of the two methods are presented. The
      detection limits of S-(-)-bevantolol were 0.1% and 0.05% for CE and HPLC method,
      respectively and R-(+)-bevantolol were 0.15% and 0.05% for CE and HPLC method,
      respectively. There was generally good agreement between the HPLC and CE results.

PMID- 17024857
TI  - Glycolysis in Plasmodium falciparum results in modulation of host enzyme
      activities.
AB  - BACKGROUND & OBJECTIVES: Plasmodium falciparum, the causative agent of the most
      serious form of malaria, infects about 5-10% of the world human population per
      year. It is well established that the erythrocytic stages of the malaria parasite
      rely mainly on glycolysis for their energy supply. In the present study, the
      glucose utilisation of erythrocyte population with parasitaemia levels similar to
      that of malaria patients was measured. The results allowed us to assess the
      effect of the parasites on the glucose utilisation of the vast majority of
      uninfected erythrocytes. METHODS: Using [2-13C]glucose and nuclear magnetic
      resonance (NMR) technique, the glucose utilisation in normal red blood cell (RBC)
      and P. falciparum infected red blood cell (IRBC) populations was measured. The
      IRBC population consisted of > 96% RBC and < 4% of parasite infected red blood
      cells (PRBC). The glycolytic enzymes were assayed to assess the effect of
      infected red cells on the enzymatic activities of uninfected ones. RESULTS: The
      rate of glucose utilisation by IRBC was considerably higher than that of RBC.
      Upon addition of 25% v/v conditioned culture medium (CM) of IRBC, RBCs exhibited
      a significant decrease in glucose utilisation. The CM could directly inhibit the
      activities of RBC glycolytic enzymes-phosphofructokinase (PFK) and pyruvate
      kinase (PK), without interfering with the activity of the pentose phosphate
      pathway enzyme-glucose-6-phosphate dehydrogenase (G-6-PD). INTERPRETATION &
      CONCLUSION: The present study showed that the clinical level of P. falciparum
      infected RBCs (< 4% parasitaemia) significantly enhance the glycolytic flux as
      well as down-regulate the glucose utilisation rate in the majority of uninfected
      RBC population. The mechanism of inhibition seems to be direct inhibition of the
      regulatory glycolytic enzymes-PFK and PK.

PMID- 17024858
TI  - The changing spectrum of severe falciparum malaria: a clinical study from Bikaner
      (northwest India).
AB  - BACKGROUND & OBJECTIVES: Recently there were reports from all over India about
      changing spectrum of clinical presentation of severe malaria. The present study
      was planned to study the same in the northwest India. METHODS: This prospective
      study was conducted on patients of severe malaria admitted in a classified
      malaria ward of a tertiary care hospital in Bikaner, Rajasthan (northwest India)
      during 1994 and 2001. It included adult patients of both sexes belonging to all
      age groups. The diagnosis of Plasmodium falciparum was confirmed by demonstrating
      asexual form of parasites in peripheral blood smear. All patients were treated
      with i.v./oral quinine. The specific complications were treated by standard WHO
      protocol. The data for individual complications for both the years were analysed
      by applying chi-square test. RESULTS: In a prospective study in 1994 the spectrum
      of complication was dominated by cerebral malaria (25.75%) followed by jaundice
      (11.47%), bleeding tendencies (9.59%), severe anaemia (5.83%), shock (5.26%),
      Acute respiratory distress syndrome-ARDS (3.01%), renal failure (2.07%) and
      hypoglycemia (2.07%) whereas in 2001 it was dominated by jaundice (58.85%)
      followed by severe anaemia (26.04%), bleeding tendencies (25.52%), shock
      (10.94%), cerebral malaria (10.94%), renal failure (6.25%), ARDS (2.08%) and
      hypoglycemia (1.56%). The sharp difference for presence of jaundice and severe
      anaemia in 2001 and cerebral malaria in 1994 was statistically significant.
      Similarly, the important cause of mortality in 2001 was multiple organ
      dysfunction syndrome (71.10%) with predominant presentation of jaundice and renal
      failure, whereas in 1994, it was cerebral malaria (77.96%). INTERPRETATION &
      CONCLUSION: The observation of changing spectrum of severe malaria in this study
      and a significant increase in presentation with jaundice as an important
      manifestation is highly essential for primary, secondary and tertiary level
      health care providers for proper diagnosis and management.

PMID- 17024859
TI  - Amplification of LDH gene from indian strains of Plasmodium vivax.
AB  - BACKGROUND & OBJECTIVES: Plasmodium vivax is geographically widespread and
      responsible for > 50% of malaria cases in India. Increased drug resistance of the
      parasite highlights the immediate requirement of early and accurate diagnosis as
      well as new therapeutics. In view of this, the present study was undertaken to
      amplify P. vivax (Indian strains) lactate dehydrogenase gene (PvLDH) which has
      been identified as a good target for antimalarials as well as diagnostics.
      METHODS: P. vivax infected clinical blood samples were collected from southern
      part of India and were tested with established diagnostic parameters (ICT, Giemsa
      staining). Total DNA was extracted from blood samples and subjected to PCR using
      two sets of primers, one for the amplification of full PvLDH gene (951 bp) and
      the other for a partial PvLDH gene fragment (422bp), covering a variable
      antigenic region (140aa) as compared to other plasmodial species. RESULTS &
      CONCLUSION: PCRs for both the full and partial gene targets were optimised and
      found to be consistent when tested on several P. vivax positive clinical samples.
      In addition, full gene PCR was found to specifically detect only P. vivax DNA and
      could be used as a specific molecular diagnostic tool. These amplified products
      can be cloned and expressed as a recombinant protein that might be useful for the
      development and screening of antimalarials as well as for diagnostic purposes.

PMID- 17024860
TI  - Mapping of risk prone areas of kala-azar (Visceral leishmaniasis) in parts of
      Bihar State, India: an RS and GIS approach.
AB  - BACKGROUND & OBJECTIVES: The kala-azar fever (Visceral leishmaniasis) is
      continuing unabated in India for over a century, now being largely confined to
      the eastern part of India mainly in Bihar state and to some extent in its
      bordering states like West Bengal and Uttar Pradesh. Two study sites namely
      Patepur block in Vaishali district with high endemicity in northern part and
      Lohardagga block in Lohardagga district with absolute non-endemicity in southern
      part of Bihar were selected for the study with the following objectives : (i) to
      study the macro-ecosystem in relation to distribution of vector -Phlebotomus
      argentipes; (ii) to identify/map the risk prone areas or villages in a block for
      quick remedial measures; and (iii) to make use of satellite remote sensing and
      GIS to demonstrate the utility for rapid assessment of landuse/landcover and
      their relation with the incidence of kalaazar leading to the mapping of risk
      prone areas. METHODS: Indian Remote Sensing (IRS)-1D LISS III satellite data for
      the periods of March and November 2000 were analysed in Silicon graphic image
      processing system using ERDAS software. False color composites (FCC) were
      generated and landuse/landcover was assessed using Maximum likelihood supervised
      classification techniques based on ground truth training sets. During the study
      the GIS functions are used to quantify the remotely sensed landscape proportions
      of 5 km2 buffer surrounding each known group of villages of high occurrence of
      sandflies in endemic and nonendemic study sites. Instead of traditional ground
      based survey methods to vector surveillance, the present study used a combination
      of remote sensing (RS) and geographical information system (GIS) approach to
      develop landscape predictors of sandfly abundance-an indicator of human vector
      contact and as a measure of risk prone areas. RESULTS: Statistical analysis using
      the remotely sensed landscape variables showed that rural villages surrounded by
      higher proportion of transitional swamps with soft stemmed edible plants and
      banana, sugarcane plantations had higher sandfly abundance and would, therefore,
      be at higher risk prone areas for man-vector contact. INTERPRETATION &
      CONCLUSION: The present study clearly brought out the usefulness of satellite
      remote sensing technology in generating the crucial information on spatial
      distribution of landuse/landcover classes with special emphasis on indicator
      landcover classes thereby helping in prioritising the area to identify risk prone
      areas of kala-azar through GIS application tools.

PMID- 17024861
TI  - A comparative study of regression of jaundice in patients of malaria and acute
      viral hepatitis.
AB  - BACKGROUND & OBJECTIVES: Jaundice is one of the common manifestations of severe
      malaria in adults. The purpose of this study is to compare the pattern of
      clinical and biochemical parameters such as serum bilirubin and liver enzyme
      levels in patients of malaria with jaundice and acute viral hepatitis.
      METHODOLOGY: The present study was conducted on 34 patients of malaria with
      jaundice and 15 patients of acute viral hepatitis. Estimation of serum bilirubin,
      aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline
      phosphatase was done daily using standard procedures in malaria patients and
      weekly in acute viral hepatitis patients. RESULTS: Mean level of serum bilirubin
      on first day in malaria and acute viral hepatitis patients was 7.07 +/- 3.94 and
      10.38 +/- 7.87 mg%, whereas on Day 8 it was 1.19 +/- 1.43 and 7.88 +/- 7.02 mg%
      respectively. Mean level of AST on Day 1 in malaria and acute viral hepatitis
      patients was 158.47 +/- 120.35 and 1418.6 +/- 834.11 IU/L, whereas on Day 8 it
      was 41 +/- 28.33 and 775.3 +/- 399.01 IU/L respectively. Mean level of ALT on Day
      1 in malaria and acute viral hepatitis patients was 220.14 +/- 145.61 and 1666.67
      +/- 1112.77 IU/L, whereas on Day 8 it was 50.85 +/- 37.31 and 823.8 +/- 475.06
      IU/L respectively. Mean level of serum alkaline phosphatase on Day 1 in malaria
      and acute viral hepatitis patients was 394.74 +/- 267.78 and 513.4 +/- 324.7
      IU/L, whereas on Day 8 it was 84.76 +/- 68.50 and 369.27 +/- 207.75 IU/L
      respectively. INTERPRETATION & CONCLUSION: We observed that resolution of
      jaundice in malaria took 1-2 weeks in contrast 6 to 8 weeks in viral hepatitis.
      This difference in duration was statistically significant. Thus, jaundice not
      resolving in 1-2 weeks time in a patient of malaria requires serious
      consideration for presence of other concomitant diseases including viral
      hepatitis.

PMID- 17024862
TI  - Multiple sclerosis: peripheral mononuclear cells inhibit Plasmodium falciparum
      growth and are activated by parasite antigens.

PMID- 17024864
TI  - Detection of some gastrointestinal parasites from four synanthropic flies in
      Ekpoma, Nigeria.

PMID- 17024863
TI  - Comparative study on the efficacy of lambdacyhalothrin and bifenthrin on torn
      nets against the malaria vector, Anopheles stephensi as assessed by tunnel test
      method.

PMID- 17024865
TI  - Clinical manifestations of severe forms of P. falciparum malaria in koraput
      district of Orissa State, India.

PMID- 17024866
TI  - Human chitotriosidase helps Plasmodium falciparum in the Anopheles midgut.

PMID- 17024867
TI  - Thrombocytopenia in Plasmodium vivax infected children.

PMID- 17024868
TI  - Treatment of ovarian cancer at the crossroads: 50 years after single-agent
      melphalan chemotherapy.

PMID- 17024869
TI  - Management of liver metastases from colorectal cancer.
AB  - The liver is a frequent site of metastatic colorectal disease. Over the past 20
      years, improvements in systemic chemotherapy and surgical techniques have
      improved the survival of patients with hepatic metastases. For 4 decades,
      fluorouracil and leucovorin were the only drugs available to treat metastatic
      colorectal cancer, but several new drugs and a variety of novel regimens are now
      available. Further improvements in results have been seen with the delivery of
      chemotherapy via the hepatic artery. Surgical resection of liver metastases has
      been encouraged when possible, and recent advances in surgery such as portal vein
      embolization, have made liver resection a possibility for more patients. This
      review considers the timing and sequence of chemotherapy and surgery in this
      setting, as well as the roles of cryoablation, radiofrequency ablation, and
      radiation therapy.

PMID- 17024870
TI  - Treatment of prostate cancer in obese patients.
AB  - Obesity is a complex, chronic disease that has reached epidemic proportions in
      the United States. Obesity is now linked with numerous health conditions,
      including many oncologic diagnoses. Its association with prostate cancer, the
      most prevalent cancer in men, has also been investigated, with studies suggesting
      a direct relationship between increasing obesity and prostate cancer mortality.
      Outcomes data for specific interventions in obese patients with prostate cancer
      have only recently begun to emerge. Surgery, while feasible even in the very
      obese, may result in less than optimal cancer control rates. Brachytherapy data
      are emerging, and are promising. No outcomes data are available for the use of
      external-beam radiation in obese patients. Long-term data for external-beam
      radiation, as well as for surgery and brachytherapy, are required to determine
      the most appropriate treatment for obese patients with prostate cancer. These
      data, coupled with a more thorough understanding of the biochemical relationship
      between obesity and prostate cancer, will be necessary to make optimal management
      decisions for obese patients with prostate cancer in the future.

PMID- 17024871
TI  - Stage III lung cancer: two or three modalities? The continued role of thoracic
      radiotherapy.
AB  - Lung cancer is the leading cause of cancer mortality in the United States. A
      significant number of patients present with disease involving mediastinal lymph
      nodes. As survival after surgery alone for stage III disease is poor, radiation
      therapy and chemotherapy have been evaluated in the neoadjuvant and adjuvant
      settings to improve outcomes. The benefit of adjuvant chemotherapy in the
      subgroup of patients with N2 disease is uncertain. Small randomized trials
      enrolling patients with stage III disease have shown a benefit of neoadjuvant
      chemotherapy over surgery alone. Whether neoadjuvant chemotherapy is superior to
      adjuvant chemotherapy is under investigation. Furthermore, whether neoadjuvant
      chemoradiotherapy is superior to neoadjuvant chemotherapy is controversial, and
      few randomized studies comparing these approaches have been reported.
      Nevertheless, neoadjuvant chemoradiotherapy appears to be associated with higher
      rates of resection, higher rates of clearance of mediastinal nodal disease, and
      better local/regional control. The use of postoperative radiation therapy (PORT)
      has declined since the publication of the 1998 meta-analysis suggested a
      detriment in survival with this strategy. However, radiation techniques are
      improving and emerging data support the use of carefully delivered PORT Finally,
      it remains unclear whether surgical resection offers an advantage over definitive
      chemoradiotherapy alone for stage III disease. In summary, locally advanced NSCLC
      remains a formidable challenge with few cures, and optimal treatment requires the
      careful use of surgery, chemotherapy, and radiation therapy.

PMID- 17024872
TI  - New questions about transplantation in multiple myeloma.
AB  - Multiple myeloma is now the most common indication for autologous stem cell
      transplantation (ASCT) in North America, with over 5,000 transplants performed
      yearly (Center for International Blood and Marrow Transplant Research [CIBMTR]
      data). While the role of ASCT as initial therapy in multiple myeloma has been
      established by randomized studies, newer therapies are challenging the
      traditional paradigm. The availability of novel induction agents and newer risk
      stratification tools, and the increasing recognition of durability of remissions
      are changing the treatment paradigm. However, even with arduous therapy designed
      to produce more complete remissions-for example, tandem autologous transplants-we
      have seen no plateau in survival curves. A tandem autologous procedure followed
      by maintenance therapy may be performed in an attempt to sustain remission.
      Sequential autologous transplants followed by nonmyeloablative allotransplants
      are pursued with the hope of "curing" multiple myeloma. We examine how the key
      challenges of increasing the response rates and maintaining responses are being
      addressed using more effective induction and/or consolidation treatments and the
      need for maintenance therapies after ASCT. We argue that given the biologic
      heterogeneity of multiple myeloma, risk-adapted transplant approaches are
      warranted. While the role of curative-intent, dose-intense toxic therapy is still
      controversial, conventional myeloablative allogeneic transplants need to be
      reexamined as an option in high-risk aggressive myeloma, given improvements in
      supportive care and transplant-related mortality.

PMID- 17024873
TI  - Disparities in cancer care among racial and ethnic minorities.
AB  - The 2005 National Health Disparities Report found disparities related to race,
      ethnicity, and socioeconomic status in the United States health-care system.
      While varying in magnitude, disparities were observed in almost all aspects of
      health care including cancer. Disparities were noted across quality and access to
      health care, levels and types of health care, various health-care settings, and
      within many subpopulations. In this review, we explore the disparities in cancer
      care among racial and ethnic minorities. In particular we consider numerous
      factors that may influence health care for racial and ethnic minority groups
      including socioeconomic issues, access, cultural beliefs, risk factors, and
      comorbidities. Although there are extensive confounding factors that vary with
      each subgroup, trends that may help individual practitioners better understand
      this complex issue become evident through closer evaluation of available data.

PMID- 17024874
TI  - Trial initiated for liposomal vincristine in relapsed/refractory acute
      lymphoblastic leukemia.

PMID- 17024875
TI  - Why integrative oncology? Complementary therapies are increasingly becoming part
      of mainstream care.

PMID- 17024876
TI  - A novel collagen hydrogel cross-linked by gamma-ray irradiation in acidic pH
      conditions.
AB  - We made a new type of collagen gel by gamma-ray irradiation of an acidic solution
      of type-I collagen, and performed comparative studies on a conventional gel and
      the new type of gel. The neutral gel, a conventional 0.3% (w/v) collagen gel, was
      formed at neutral pH and then irradiated by gamma-rays. The acidic gel, a 0.3%
      (w/v) collagen gel, was formed directly from the acidic solution of collagen by y
      ray irradiation. Both types of gel were prepared, swollen in water and then dried
      for the measurement of specific water content. The neutral gel showed a
      relatively high specific water content and shrunk moderately, depending on the
      dose, while the acidic gel showed lower specific water content and shrunk clearly
      by y-ray irradiation. A three-dimensional tangled network of microfibrils was
      clearly observed in the neutral gels by scanning electron microscopy, but not in
      the acidic gels. From these results, we concluded that the acidic gel was quite
      different from a conventional collagen gel. Sodium dodecylsulfate-polyacrylamide
      gel electrophoresis showed that the alpha1 subunit and alpha2 subunit of the
      collagen molecule were cross-linked. The triple-helical structure of collagen was
      only partially perturbed, but not denatured completely, because the circular
      dichroism spectrum of the collagen solution irradiated at 1.3 kGy was similar to
      that of native collagen solution. Amino-acid analysis revealed that tyrosine,
      phenylalanine and histidine decreased by irradiation in the neutral gel. In the
      case of the acidic gel, these three amino acids and methionine decreased. We
      considered that these amino acids were cross-linking points between the collagen
      subunits during the gamma-ray irradiation.

PMID- 17024877
TI  - Hepatocyte spheroid culture on a polydimethylsiloxane chip having microcavities.
AB  - A two-dimensional microarray technique of spherical multicellular aggregates
      (spheroids) using a microfabricated polydimethylsiloxane (PDMS) chip and the
      expression of liver-specific functions of primary rat hepatocytes on the chip
      were investigated. The PDMS chip, which was fabricated by a photolithography
      based technique, consisted of approximately 2500 cylindrical microcavities
      (approximately 1100 cavities/cm2) in a triangular arrangement of 330 microm pitch
      on a PDMS plate (20 x 20 mm); each cavity measured 300 microm in diameter and 100
      microm in depth. Most hepatocytes on the PDMS chip gradually gathered and
      subsequently formed a single spheroid in each cavity until 3 days of culture. A
      part of the spheroid was attached to the bottom or wall surface of the
      microcavity, and the spheroid configuration was maintained for at least 14 days
      of culture. Albumin secretion, ammonia removal and ethoxyresorufin O-dealkylase
      (EROD) activity, which is a cytochrome P-450-dependent reaction, of hepatocytes
      on the PDMS chip were higher than those of a monolayer dish or a flat PDMS dish
      without microcavities, and were maintained for at least 10 days of culture. The
      spheroid microarray technique appears to be promising in the development of cell
      chips and microbioreactors.

PMID- 17024878
TI  - Multifunctional conjugation of proteins on/into bio-nanoparticles prepared by
      amphiphilic poly(gamma-glutamic acid).
AB  - The present study focuses on nanoparticles composed of amphiphilic poly(gamma
      glutamic acid) (gamma-PGA) as potential protein carriers. Amphiphilic graft co
      polymers composed of y-PGA as the hydrophilic backbone and L-phenylalanine
      ethylester (L-PAE) as the hydrophobic segment were synthesized by grafting L-PAE
      to y-PGA using water-soluble carbodiimide (WSC). Due to their amphiphilic
      properties, the gamma-PGA-graft-L-PAE co-polymer formed monodispersed
      nanoparticles in water. The particle size of the nanoparticles composed of gamma
      PGA-graft-L-PAE (gamma-PGA nanoparticles) was about 200 nm and showed a highly
      negative zeta potential. To evaluate their potential applications as
      multifunctional protein carrier, we prepared protein-entrapped gamma-PGA
      nanoparticles by encapsulation, covalent immobilization or physical adsorption
      methods. For this purpose, 11 different proteins with various molecular weights
      and isoelectric points (pI values) were used as model proteins. The encapsulation
      of the protein into the nanoparticles was observed for all tested proteins. The
      amount of protein covalently immobilized or adsorbed onto the nanoparticles
      showed different tends based on the molecular weight and pI of each protein.
      Positively charged proteins could be adsorbed onto the negatively charged
      nanoparticles by electrostatic interaction. Moreover, it was found that enzyme
      encapsulated nanoparticles showed higher enzymatic activity than surface
      immobilized nanoparticles. These results indicated that the enzymatic activity of
      the enzyme-entrapped nanoparticles was significantly affected by the conjugation
      method, and that encapsulation was the optimal method for the conjugation of
      proteins and nanoparticles. It is expected that the y-PGA nanoparticle will have
      great potential as multifunctional carriers in pharmaceutical and biomedical
      applications, such as drug and vaccine delivery systems.

PMID- 17024879
TI  - Molecular aspects of microparticle phagocytosis by dendritic cells.
AB  - The ability of immature dendritic cells (iDCs) derived from human peripheral
      blood mononuclear cells to phagocytose poly(lactic-co-glycolic acid) (PLGA)
      microparticles (MPs) as compared to polystyrene MPs and the molecular aspects of
      this phagocytosis were investigated. Treating iDCs with PLGA or polystyrene
      fluorospheres of approximately 3 microm in diameter resulted in the
      internalization of the particles as evidenced by confocal laser scanning
      micrographs. This uptake of fluorospheres by DCs was decreased by pretreatment of
      cells with cytochalasin D or by incubation with the fluorospheres at 4 degrees C,
      and was sensitive to EDTA and trypsin pretreatments in a dose-dependent manner.
      In agreement with our previous studies, treatment of iDCs with PLGA MPs, but not
      with polystyrene MPs, led to DC maturation, as measured by increase in release of
      the autocrine maturation cytokine, tumor necrosis factor-alpha, which was
      dependent on ratio of PLGA MPs to DCs. Taken together, this work begins to
      address the role of phagocytosis on PLGA MP-induced DC maturation and the
      molecular mechanisms involved.

PMID- 17024880
TI  - Formulation, characterization and release studies of alginate microspheres
      encapsulated with tetanus toxoid.
AB  - Alginate is a safe, non-immunogenic and inexpensive natural polymer with high
      mucoadhesive properties. Alginate microspheres can be used as a delivery system
      for antigens to mucosal surfaces. In the present study alginate microspheres were
      prepared by an emulsification technique. The effects of sonication time,
      concentration of alginate, emulsifier and calcium chloride, and also the volume
      of calcium solution, were evaluated on mean size, size range, surface roughness
      and porosity, sphericity and clumping of microspheres using an optical microscope
      and particle size analyzer. The most desirable conditions were 90 s sonication,
      3% alginate solution, 2% surfactant and 60 ml of 0.33% CaCl2 in octanol. The
      resulting microspheres had a mean size of 1.34 +/- 0.3 microm and size range of
      0.3 +/- 2.0 microm, with no surface roughness and porosity, low clumping and high
      sphericity. The encapsulation efficiency was about 47.7%. All batches showed
      nearly the same release profiles with a low burst release. The stability of the
      model antigen (tetanus toxoid (TT)) extracted from microspheres was confirmed by
      SDS-PAGE; and the antigenicity of TT was studied by ELISA and found to be 91 +/-
      5% of the original TT. It can be concluded that, with regard to the size and
      morphological characteristics of the prepared microspheres and their ability in
      preserving the antigenicity of the encapsulated TT, they could be used as a
      delivery system for mucosal delivery of TT.

PMID- 17024881
TI  - The use of poly(lactic-co-glycolic acid) microspheres as injectable cell carriers
      for cartilage regeneration in rabbit knees.
AB  - The use of injectable scaffolding materials for in vivo tissue regeneration has
      raised great interest because it allows cell implantation through minimally
      invasive surgical procedures. Previously, we showed that poly(lactic-co-glycolic
      acid) (PLGA) microspheres can be used as an injectable scaffold to engineer
      cartilage in the subcutaneous space of athymic mice. The purpose of this study
      was to determine whether PLGA microspheres can be used as an injectable scaffold
      to regenerate hyaline cartilage in the osteochondral defects of rabbit knees. A
      full-thickness wound to the patellar groove of the articular cartilage was made
      in the knees of rabbits. Rabbit chondrocytes were mixed with PLGA microspheres
      and injected immediately into these osteochondral wounds. Both chondrocyte
      transplantations without PLGA microspheres and culture medium injections without
      chondrocytes served as controls. Sixteen weeks after implantation, chondrocytes
      implanted using the PLGA microspheres formed white cartilaginous tissues.
      Histological scores indicating the extent of the cartilaginous tissue repair and
      the absence of degenerative changes were significantly higher in the experimental
      group than in the control groups (P < 0.05). Histological analysis by a
      hematoxylin and eosin stain of the group transplanted with microspheres showed
      thicker and better-formed cartilage compared to the control groups. Alcian blue
      staining and Masson's trichrome staining indicated a higher content of the major
      extracellular matrices of cartilage, sulfated glycosaminoglycans and collagen in
      the group transplanted with microspheres than in the control groups. In addition,
      immunohistochemical analysis showed a higher content of collagen type II, the
      major collagen type in cartilage, in the microsphere transplanted group compared
      to the control groups. In the group transplanted without microspheres, the wounds
      were repaired with fibro-cartilaginous tissues. This study demonstrates the
      feasibility of using PLGA microspheres as an injectable scaffold for cartilage
      regeneration in a rabbit model of osteochondral wound repair.

PMID- 17024882
TI  - Poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide)-g-poly(1,3trimethylene
      carbonate) amphiphilic graft co-polymer as a potential drug carrier.
AB  - A biodegradable amphiphilic graft polymer was successfully synthesized by
      grafting hydrophobic poly(1,3-trimethylene carbonate) (PTMC) sequences onto a
      hydrophilic poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide) (PHEA) backbone.
      The graft polymer, PHEA-g-PTMC, was synthesized by ring-opening polymerization
      initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any
      catalyst. The graft polymer was characterized by Fourier transform infrared
      spectroscopy, 1H-nuclear magnetic resonance spectroscopy, combined size-exclusion
      chromatography and multiangle laser light scattering analysis. Two drugs with
      distinct water solubility, prednisone acetate and tegafur, were encapsulated in
      the PHEA-g-PTMC nanoparticles. The in vitro release of two drugs from PHEA-g-PTMC
      nanoparticle drug-delivery systems was investigated.

PMID- 17024883
TI  - Business and midwifery.

PMID- 17024884
TI  - Midwifery model of care--phase II: newborn care.

PMID- 17024885
TI  - Marion's message. Working in Afghanistan with Siri.

PMID- 17024886
TI  - The business of birthing: the write way to more clients.

PMID- 17024887
TI  - Shari Daaniels: maverick midwife blazes trails and births babies on TV.

PMID- 17024888
TI  - C-sections, breastfeeding and bugs for your baby: what the doctor probably won't
      tell you.

PMID- 17024889
TI  - Profits and rewards--why don't midwives earn high salaries?

PMID- 17024890
TI  - A Vermont homebirth.

PMID- 17024891
TI  - Is my baby yellow?
AB  - In July 2004, The American Academy of Pediatrics (AAP) summarized the latest
      medical research regarding newborn jaundice and updated the current clinical
      guidelines. The AAP recommends that clinicians 1) promote breastfeeding and not
      routinely supplement newborns with water; 2) assess the risk of severe
      hyperbilirubinemia before discharge; 3) provide follow-up visits after discharge
      to assess jaundice; and 4) when indicated, treat newborns with phototherapy or
      exchange transfusion to prevent the development of severe hyperbilirubinemia and
      kernicterus. This article summarizes the new guidelines.

PMID- 17024892
TI  - Jaundice dictionary.

PMID- 17024893
TI  - Midwifery and malpractice.

PMID- 17024894
TI  - Experiential learning for childbirth.

PMID- 17024895
TI  - "Hands-off" care and birth as an out-of-body experience.

PMID- 17024896
TI  - Wild geese and a heron.

PMID- 17024897
TI  - Developing a freelance midwifery consultancy business.

PMID- 17024898
TI  - Probiotics: a better way to treat infections during pregnancy.

PMID- 17024899
TI  - GBS in a homebirth setting.

PMID- 17024900
TI  - Voluntary licensure.

PMID- 17024901
TI  - Supporting mothers in long-term breastfeeding.

PMID- 17024902
TI  - Tax tips for independent midwives.

PMID- 17024903
TI  - Caleb.

PMID- 17024904
TI  - The business of midwifery customizing the superbill.

PMID- 17024905
TI  - Guatemala information questioned.

PMID- 17024906
TI  - Indonesia needs help.

PMID- 17024907
TI  - Do I have to leave my country and home to have my baby sanely?

PMID- 17024908
TI  - Hope in Uganda.

PMID- 17024909
TI  - Stories from Senegal.

PMID- 17024910
TI  - Getting back to nature: non-medical birth options in Athens, Greece.

PMID- 17024911
TI  - Eve's Foundation.

PMID- 17024912
TI  - "Let's fika first"! A look at Swedish midwifery from a cultural perspective.
AB  - Sweden is the third largest country in Europe and has a population of
      approximately nine million people. Swedish midwives are highly esteemed,
      autonomous and respected by the population. This article discusses cultural
      aspects of working as a midwife in Sweden along with the obstacle of learning a
      new language and various new methods of midwifery care. This personal account of
      my placement in Sweden is intended to offer insight to midwives and nurses who
      may contemplate working there.

PMID- 17024913
TI  - Breaking the silence.

PMID- 17024914
TI  - The Dear Abby of addiction.

PMID- 17024915
TI  - A shot at quitting.

PMID- 17024916
TI  - Putting a face on addiction.

PMID- 17024918
TI  - Quality improvement pervades all we do.

PMID- 17024917
TI  - Consuming culture.

PMID- 17024919
TI  - MMA urges USDA to drop juice from WIC-eligible foods.

PMID- 17024920
TI  - When you suspect a drug problem.

PMID- 17024921
TI  - Beyond addiction.

PMID- 17024923
TI  - A road less traveled.

PMID- 17024922
TI  - Meth turns 40.

PMID- 17024924
TI  - Patients with pain and addiction: what's a doctor to do?
AB  - Significant improvements in the evaluation and treatment of pain have led to more
      prescribing of and increased pressure to prescribe a variety of potentially
      addictive drugs to patients who are suffering from acute and chronic pain.
      Although these drugs serve an important purpose, they present risks to patients
      who are in recovery from addiction, are currently addicted, or have a family
      history of addiction. This article presents an overview of the concerns
      physicians face when treating such patients and outlines strategies for safely
      using these drugs.

PMID- 17024925
TI  - Medication management of pathological gambling.
AB  - Pathological gambling has received little attention from clinicians and
      researchers despite prevalence rates similar to or greater than those of
      schizophrenia and bipolar disorder. This article summarizes the phenomenology and
      associated psychopathology of this public health problem and presents results of
      studies of 3 types of pharmacological agents used to treat this disorder:
      serotonin reuptake inhibitors, opioid antagonists, and mood stabilizers.

PMID- 17024926
TI  - Marijuana and adolescents.
AB  - Marijuana is the most frequently used illicit drug in the United States. The
      health risks associated with its use are underestimated by adolescents, their
      parents, and health care providers. This article identifies current trends
      regarding marijuana use among adolescents and provides a summary of current
      information about the risks of marijuana use for both users and society at large.
      It also urges physicians and other health care providers to be aware of the
      dangers of marijuana as well as the subtle and seemingly unexplained changes in
      adolescent behavior belying its use. In addition, it calls attention to the
      magnitude of the problem of marijuana use among teens; the importance of
      educating adolescents and parents-and the community at large-about the prevalence
      of its use, how to detect use, and its associated effects on health; and the need
      for professional counseling for youths who are using the drug.

PMID- 17024927
TI  - On time clocks and taking time.

PMID- 17024928
TI  - A brief history medical diagnosis and the birth of the clinical laboratory. Part
      5a- the foundation of molecular science and genetics.

PMID- 17024929
TI  - What the 1918 flu pandemic teaches us. Yesterday's lessons inform today's
      preparedness.

PMID- 17024930
TI  - Quality collection: the phlebotomist's role in pre-analytical errors.

PMID- 17024931
TI  - Developing your ISBT 128 implementation plan. 12 things to consider in preparing
      for the new standard.

PMID- 17024932
TI  - George Kennedy and Leica jion art with science.

PMID- 17024933
TI  - MLTs sail on the high seas and explore the ocean's treasures.

PMID- 17024934
TI  - Supporting troops through USERRA.

PMID- 17024935
TI  - HIV testing: an update.

PMID- 17024936
TI  - Is your organization ethically fit?

PMID- 17024937
TI  - Wake up and smell the demographics.

PMID- 17024938
TI  - A 24-month follow-up of flowable resin composite as an intermediate layer in non
      carious cervical lesions.
AB  - This study compared the clinical performance of a microhybrid resin composite to
      lined Class V restorations or to those restorations without a flowable resin
      composite over a 24-month period. Nineteen patients with at least 2 pairs of
      equivalent cervical erosion/attrition/abfraction lesions, under occlusion, were
      enrolled in this study. A total of 74 restorations were placed, half for each
      group (Single-Bond + Filtek-Flow + Filtek Z250 or Single-Bond + Filtek Z250).
      According to the manufacturers' instructions, 2 calibrated operators placed all
      restorations. Two other independent examiners evaluated the restorations at
      baseline and after 24 months, according to the USPHS criteria and modified
      criteria for color match. The classic alpha score was divided into A1 for "not
      detectable" and A2 for "slightly discernible" filling. Statistical analysis was
      conducted using Fisher's exact test (alpha=0.05). For each group, 8 restorations
      were lost after 24 months (retention rate of 89.2%). All the restorations showed
      a trend toward dark yellowing after 24 months (color match A2).

PMID- 17024939
TI  - 2-year Clinical evaluation of sodium hypochlorite treatment in the restoration of
      non-carious cervical lesions: a pilot study.
AB  - This pilot study evaluated the effect of removing acid-etch-exposed dentin
      collagen on the clinical performance of composite restorations of noncarious
      cervical lesions placed using 2 different adhesive systems. Fifty-six
      restorations were placed in 14 subjects, each subject receiving at least 4
      restorations. No cavity preparation or mechanical retention form was used. The
      variables tested were: 1) dentin treatment prior to application of the adhesive
      (acid-etch only vs acid-etch and collagen removal) and 2) type of adhesive
      (acetone- vs ethanol-based). For the acid-etch only groups, enamel and dentin
      were etched with 37% phosphoric acid for 15 seconds, rinsed and blot dried. Prime
      & Bond 2.1 (Dentsply Caulk) or Single Bond (3M ESPE) was applied and light-cured
      according to the manufacturer's instructions. For the acid-etch and collagen
      removal groups, the enamel and dentin were etched and rinsed in the same manner
      and a 10% sodium hypochlorite (NaOCl) solution was applied for 60 seconds and
      rinsed before adhesive application. Filtek Z-250 (3M ESPE) was applied to all
      specimens and light-cured according to the manufacturer's instructions, and the
      restorations were finished and polished immediately. The restorations were
      evaluated for pre- and post-operative sensitivity, retention, marginal staining
      and secondary caries at baseline, 12 and 24 months after placement, using
      modified USPHS criteria. Data were analyzed using the Kruskal-Wallis and Wilcoxon
      statistical tests (p=0.05). At 24 months, the retention rates for Prime & Bond
      2.1 with and without NaOCl pretreatment were 80% and 63%, respectively. The
      corresponding retention rates for Single Bond were 70% and 90%. Marginal staining
      was minimal. Statistical analyses revealed no significant differences at any time
      interval between groups for retention or marginal staining. No post-operative
      sensitivity or secondary caries was detected during the study.

PMID- 17024940
TI  - Influence of bleaching agents and desensitizing varnishes on the water content of
      dentin.
AB  - This in vitro study investigated the possible dehydration of dentin caused by
      bleaching agents. Furthermore, it tested whether protective dentin varnishes can
      maintain the physiological moisture of dentin during bleaching treatment. Fifty
      five standardized dentin cylinders were prepared from freshly extracted bovine
      incisors under constant water irrigation. Prior to bleaching, the treatment
      specimens were conditioned at room temperature in a hygrophor for 14 days. The
      samples were divided into 11 groups. The Group A specimens, which were completely
      dehydrated, and Group B, which was stored for 2 weeks in a hygrophor, served as
      controls (A, B n=5). The other samples (n=10 each group) were coated with
      Vivasens [VS] (C), Bilfuorid [BF] (D) and Seal&Protect [SP] (E). Five specimens
      from each group (C-E) were subsequently treated with an experimental bleaching
      gel (Exp BG) (20% carbamide peroxide [CP], glycerine-based gel): Cb, Db, Eb. The
      remaining specimens were bleached with Exp BG (F) only, Vivastyle (G: 16% CP,
      glycerine-based gel) or Vivastyle Paint On (H: 6% CP-varnish) for 7 days (n=5
      each group) with bleaching time for gels: 2 hours/day, paint on: 20 minutes/day.
      After the respective treatments, the overall water content of each specimen was
      determined using the analytical method of Karl-Fischer-titration. The water
      content of bovine dentin (Group B, mean%+/-SD) obtained in this study amounted to
      15.24+/-0.4. All bleaching products significantly reduced the water content
      compared to the controls (exp BG: 13.32+/-0.47, Vivastyle 13.2+/-0.27, paint on
      13.72+/-0.54; p<0.05). Also, application of SP before bleaching resulted in
      reduced water content (14.06+/-0.12; p=0.0005). However, bleaching with exp BG
      following use of VS (14.99+/-0.42) or SP (13.85+/-0.26) did not result in a
      reduction of water content in dentin. Pretreatment with BF did not protect dentin
      from water loss during bleaching (12.44+/-0.38; bi p=0.0009). All glycerine-based
      bleaching products used in this study had a significant dehydrating effect on
      dentin. The application of protective varnishes prior to bleaching treatment may
      reduce or even prevent dentin dehydration.

PMID- 17024941
TI  - Performance of a conventional sealant and a flowable composite on minimally
      invasive prepared fissures.
AB  - Three different fissure preparation procedures were tested and compared to the
      non-invasive approach using a conventional unfilled sealant and a flowable
      composite. Eighty permanent molars were selected and divided into 4 groups of 20
      teeth each. All the teeth were split into 2 halves, and the exposed fissures were
      photographed under a microscope (35x) before and after being prepared using the
      following methods: (I) Er:YAG laser (KEY Laser, KaVo) 600 mJ pulse energy, 6 Hz;
      (II) diamond bur; (III) Er: YAG laser (KEY Laser, KaVo) 200 mJ pulse energy, 4
      Hz; (IV) Control group: Powder jet cleaner (Prophyflex, KaVo, Germany). The pre
      and postimages were superimposed in order to evaluate the amount of hard tissue
      removed. Ten teeth in each group were then acid etched and sealed with an
      unfilled sealant (Delton opaque, Dentsply), while the remaining 10 teeth were
      acid etched, primed and bonded (Prime & Bond NT, Dentsply) and sealed with a
      flowable composite (X-flow, DeTrey, Dentsply). Material penetration and
      microleakage were evaluated after thermocycling (5000 cycles) and staining with
      methylene blue 5%. ANOVA and Mann-Whitney tests were applied for statistical
      analysis. The laser 600 mJ and bur eliminated the greatest amount of hard tissue.
      The control teeth presented the least microleakage when sealed with Delton or X
      flow. A correlation between material penetration and microleakage could not be
      statistically confirmed. Mechanical preparation prior to fissure sealing did not
      enhance the final performance of the sealant.

PMID- 17024942
TI  - Efficiency of 4 caries excavation methods compared.
AB  - This in vitro study compared the efficiency (time taken to excavate and
      successfully remove bacterially infected dentin) of Fluorescence Aided Caries
      Excavation (FACE), caries detector dye (CD), chemomechanical excavation (CS) and
      conventional excavation (CE). Teeth with dentin caries were assigned to 4 groups
      (n= 25). Caries excavation was carried out by one operator. In the FACE group,
      the operating field was illuminated with violet light. The operator observed the
      teeth through a high-pass filter and removed orange-red fluorescing areas with a
      slow speed bur. In the CS group, Carisolv was applied to the cavity using CS hand
      instruments and allowed to act for 30 seconds before caries was removed. In the
      CD group, caries was removed using the Caries Detector and, in the CE group,
      conventional excavation was carried out using visual-tactile criteria. The
      excavation time was recorded. Undecalcified thin slices (8 microm) were prepared,
      stained with giemsa and examined using light microscopy. The excavation time
      (median) was significantly shorter for FACE (3 minutes, 3 seconds) compared to CS
      (5 minutes, 8 seconds, p=0.015), CD (5 minutes, 26 seconds, p=0.003) and CE (4
      minutes, 2 seconds, p=0.025). Histology showed remaining bacteria in
      significantly fewer (5/25) FACE samples compared to CS (15/25 p=0.004) CD (12/25
      p=0.037) but not significantly fewer than CE (11/25 p=0.069). IN CONCLUSION: the
      excavation result with FACE is equal to CE and superior to CD and CS but requires
      a significantly shorter excavation time.

PMID- 17024943
TI  - Influence of resin composite shade and location of the gingival margin on the
      microleakage of posterior restorations.
AB  - OBJECTIVE: The objective of this in vitro study was to evaluate the influence of
      resin composite shade and location of the gingival margin (enamel or dentin) on
      the microleakage of proximal restorations on posterior teeth. METHODS AND
      MATERIALS: Sixty freshly extracted human third molars were prepared with
      standardized Class II box-shaped cavities with proportional size and shape, with
      distal gingival margins located on the enamel and mesial gingival margins on
      dentin. The teeth were randomly divided into 6 groups according to resin shade
      (n=10): G1-Incisal; G2-A1; G3-A2; G4-A3; G5-A3.5; G6-A4. The cavities were
      restored with a total-etch 1-bottle adhesive system and microhybrid resin
      composites inserted in 4 increments, light cured for 20 seconds through the
      occlusal surface, then an additional 60 seconds for each surface. After 1 week of
      immersion in distilled water, the specimens were thermocycled (500 cycles, 5
      degrees -55 degrees C, 30 seconds dwell time), sealed with nail polish and
      immersed in 0.5% basic fuschin solution for 24 hours. The restorations were
      sectioned longitudinally, and microleakage was evaluated using a 0-3 score scale.
      RESULTS: Data were subjected to Kruskal-Wallis and Wilcoxon tests at p<0.05. No
      statistically significant differences between groups were observed regarding the
      shade of resin composite (p=0.8570). When margins (enamel or dentin) were
      considered separately, statistically significant differences were observed
      between groups (p<0.0001), with enamel margins exhibiting lower degrees of
      microleakage. CONCLUSION: The variation of resin composite shades utilized in
      this study did not influence the microleakage of Class II restorations. However,
      the location of the gingival margin influenced the microleakage.

PMID- 17024944
TI  - Influence of additional adhesive application on the microtensile bond strength of
      adhesive systems.
AB  - This study evaluated microtensile bond strength (pTBS) when an additional
      adhesive layer was applied to the dentin surface. Thirty-five human third molars
      were flattened to expose the occlusal dentin surface. The teeth were randomly
      assigned to 7 experimental groups: G1-Single Bond (SB); G2-additional layer of
      SB; G3--a layer of Scotchbond Multi-purpose (SMP) adhesive applied over SB; G4
      Clearfil SE Bond (CE); G5-additional layer of CE; G6-Adper Prompt (AP) and G7
      additional layer of AP. For the G2, G3, G5 and G7 groups, the first adhesive
      layer was light-cured before application of the additional layer. After bonding
      procedures, 5-mm high composite crowns were incrementally built up. The samples
      were sectioned to obtain 0.9 x 0.9 beams, which were tested under tension at a
      crosshead speed of 0.5-mm/minute until failure. The failure mode and adhesive
      thickness were evaluated under SEM. The pTBS data were analyzed by 1-way ANOVA
      and post-hoc Ducan's Test (a=0.05). Mean adhesive thickness was analyzed by 1-way
      ANOVA and post-hoc Tukey's test (a=0.05). The results indicated that G3 presented
      the highest microTBS and the thickest adhesive layer. G6 and G7 presented the
      lowest microTBS values. When solvent-free adhesives systems were used, microTBS
      values were not affected by the thicker layer.

PMID- 17024945
TI  - Bonding efficacy of single-step self-etch systems to sound primary and permanent
      tooth dentin.
AB  - Currently, there is little information regarding the bonding efficacy of single
      step self-etch systems to primary tooth dentin. This study examined the
      microtensile bond strength of single-step self-etch systems (Clearfil tri-S Bond
      and One-Up Bond F Plus) to sound primary and permanent tooth dentin. Adhesives
      were applied to flat samples of primary and permanent tooth dentin, and resin
      composites were bonded according to the manufacturers' instructions. After 24
      hours of storage in distilled water at 37 degrees C, hour glass-shaped specimens
      were produced. They were subjected to microtensile testing at a crosshead speed
      of 1.0 mm/minute. The results were analyzed using 2-way analysis of variance
      (ANOVA) followed by the Tukey HSD post-hoc test (alpha=0.05). Field-emission
      scanning electron microscopy (FE-SEM) observations of the adhesive-treated dentin
      surfaces and the resin/dentin interface were also conducted. The bond strengths
      of primary tooth dentin were significantly lower than that of permanent tooth
      dentin for both self-etch systems: 44.7 +/- 10.4 versus 54.3 +/- 9.0 MPa for
      Clearfil tri-S Bond and 40.6 +/- 9.9 versus 50.0 +/- 8.7 MPa for One-Up Bond F
      Plus (p<0.001). There was no statistically significant interaction between the
      type of adhesive system and the dentin substrate (p=0.957). Although there was no
      statistically significant difference in the mean values among the different
      adhesive systems (p=0.094), there was a statistically significant difference in
      mean values among the different dentin substrates (p<0.001), which were lower for
      primary tooth dentin than for permanent tooth dentin. The failure modes were also
      independent of the type of dentin but dependent on the adhesive systems, an equal
      distribution among the 3 types of failure for Clearfil tri-S Bond and cohesive
      failures in adhesives for One-Up Bond F Plus. FE-SEM observations of dentin to
      which adhesive had been applied revealed that the smear layer had been removed
      and the collagen fibers exposed. Though the bond strengths to primary tooth
      dentin were lower than to permanent tooth dentin, excellent adaptation of the
      single-step self-etch systems to both dentin substrates was observed by FE-SEM.
      Further studies are required to determine the long-term clinical performance of
      these adhesive systems when applied to primary tooth dentin.

PMID- 17024946
TI  - Influence of the finishing technique on surface roughness of dental porcelains
      with different microstructures.
AB  - This study compared the surface roughness of 4 dental porcelains with different
      microstructures (d.Sign-D, Finesse-F, Noritake-N and Symbio-S) using varied
      surface treatments. The porcelain surfaces were submitted to the following
      surface treatments: 1) g (glazing only); 2) rg (polishing with a rubber wheel
      before glazing); 3) 2g (reglazing); 4) r (rubber wheels); 5) rp (rubber wheels +
      diamond paste); 6) d (sandpaper discs) and 7) dp (sandpaper discs + diamond
      paste). Treatments 3 through 7 were performed after breaking the glaze layer with
      a diamond bur. Surface roughness (Ra, in m) was determined using a profilometer
      (n=10). Visual inspection was made using the scanning electron microscope.
      Microstructural characterization was also performed (hardness, leucite content
      and particle size). Reglazed specimens presented significantly rougher surfaces
      compared to glazed specimens. The use of a polishing paste after the sandpaper
      discs or after the rubber wheel resulted in a reduction of the Ra value for all
      materials (except for the dp group of porcelain S). Rubber or discs followed by
      diamond paste were the best surface treatments for porcelains D (D-rp: 0.21 +/-
      0.06 microm and D-dp: 0.22 +/- 0.05 microm) and F (F-rp and F-dp: 0.17 +/- 0.03
      microm). For porcelains N and S, both reglazing (2g) and the use of rubber or
      sandpa- per discs followed by diamond paste (groups rp and dp) resulted in
      similar roughness (N-2g: 0.22 +/- 0.03 microm; N-rp: 0.22 +/- 0.04 microm; N-dp:
      0.20 +/- 0.04 microm, S-2g: 0.22 +/- 0.04 microm; S-rp: 0.19 +/- 0.04 microm; S
      dp: 0.23 +/- 0.04 microm). CONCLUSION: The best choice of surface treatment for
      leucite-based porcelains depended on the material considered. Porcelains with
      lower leucite content (F and S) tended to present lower roughness compared to
      those with higher leucite content after being polished with rubbers or discs
      followed by diamond pastes.

PMID- 17024947
TI  - Effect of early water exposure on the strength of glass ionomer restoratives.
AB  - This study examined the effect of early water exposure on the shear strength of a
      spectrum of glass ionomer restoratives. The materials evaluated included
      conventional auto-cured (Fuji II [FT], GC), resin-modified light-cured (Fuji II
      LC [FL]) and, recently introduced, high strength auto-cured (Fuji IX GP Fast
      [FN], GC; Ketac Molar Quick [KQ], 3M-ESPE; Ketac Molar [KM], 3M-ESPE) cements.
      Sixteen specimens (8.7-mm in diameter and 1-mm thick) of each material were
      prepared in metal washers and randomly divided into 2 groups. The specimens were
      allowed to set for 6 minutes between polyester strips, to ensure completion of
      the initial set. The strips were subsequently removed, and the surfaces of Group
      1 specimens were coated on both sides with resin (Fuji Coat LC, GC) and light
      cured for 10 seconds. Group 2 specimens were left uncoated. All specimens were
      then conditioned in distilled water at 37 degrees C for 4 weeks. After
      conditioning, the specimens were restrained with a torque of 2.5 Nm and subjected
      to shear punch testing using a 2-mm diameter punch at a crosshead speed of 0.5
      mm/minute. The mean shear strengths of the materials were computed and subjected
      to Independent Samples t-test and ANOVA/Scheffe's tests at significance level
      0.05. Mean strength ranged from 78.34 to 99.36 MPa and 79.88 to 95.78 MPa for
      Groups 1 and 2, respectively. No significant difference in shear strength was
      observed between the 2 groups. For both groups, KM and KQ were significantly
      stronger than FT. Contrary to current teaching, early exposure to water did not
      weaken glass ionomer restoratives. A marginal increase in strength was actually
      observed for some materials.

PMID- 17024948
TI  - Microtensile bond strength of glass ionomer cements to artificially created
      carious dentin.
AB  - In this laboratory study, the microtensile bond strengths of a conventional glass
      ionomer cement (GIC) and a resin modified glass ionomer cement (CRMGIC) to
      artificially created carious dentin and sound dentin were compared, and the
      ultrastructural morphology of the fractured interface was examined with a low
      vacuum scanning electron microscope (SEM). The specimens were divided into 4
      groups: 1) a conventional GIC (Ketac-Fil Plus Aplicap) placed on sound dentin; 2)
      a conventional GIC placed on artificially created carious dentin; 3) an RMGIC
      (Photac-Fil Aplicap) placed on sound dentin and 4) an RMGIC placed on
      artificially created carious dentin. Artificial carious lesions were created
      using a chemical demineralizing solution of 0.1 M/L lactic acid and 0.2%
      carbopol. GIC buildups were made on the dentin surfaces according to the
      manufacturer's directions. After storage in distilled water at 37 degrees C for
      24 hours, the teeth were sectioned vertically into 1 x 1 x 8-mm beams for the
      microtensile bond strength test. The microtensile bond strength of each specimen
      was measured, and failure mode was determined using an optical microscope (40x).
      The fractured surfaces were further examined with SEM. Two-way analysis of
      variance showed that the mean microtensile bond strengths of a GIC and an RMGIC
      to carious dentin were significantly lower than those to sound dentin, and the
      mean microtensile bond strengths of Photac-Fil to both sound and carious dentin
      were significantly higher than those of Ketac-Fil Plus. Chi-square tests
      indicated that there was a significant difference in failure mode between the
      sound dentin and carious dentin groups. In sound dentin groups, cohesive failure
      in GIC was pre- dominant; whereas, mixed failure was predominant in carious
      dentin groups. SEM examination showed that the specimens determined to be
      cohesive failures under light microscopy in the Photac-Fil/Sound Dentin group
      were actually mixed failures under high magnification of SEM.

PMID- 17024949
TI  - Change of color and translucency by light curing in resin composites.
AB  - OBJECTIVE: This study evaluated color and translucency changes caused by light
      curing resin composite materials. METHODS: The CIELAB parameters (L*, a* and b*)
      of disks of A2 and opaque A2 shades of Charisma (Heraeus-Kulzer), Solare (GC) and
      Filtek Supreme (3M) were evaluated on the backings of black, white and the
      material itself both before and after light curing to evaluate color and
      translucency changes (by means of calculating deltaE* and the translucency
      parameter, respectively). RESULTS: Solare and Filtek Supreme showed significantly
      smaller color changes during light curing than Charisma; however, the value of
      deltaE* of all the products/shades was still in the clinically unacceptable
      range. Regarding translucency changes during light curing, the A2 and opaque A2
      shades of Charisma showed a statistically significant increase, although no
      difference was observed in the other products. CONCLUSIONS: Solare and Filtek
      Supreme tended to show less changes in translucency and color during light curing
      compared to Charisma. Nevertheless, the changes in color during light curing were
      still in the range of unacceptable color change. Therefore, direct shade matching
      of these materials for a precise shade match should be performed by using the
      cured material.

PMID- 17024950
TI  - Influence of Nd:YAG laser irradiation on an adhesive restorative procedure.
AB  - Hard tissue modification by means of laser irradiation is becoming popular in
      dentistry, since it promotes assorted responses between the tooth and the
      restorative material. Some studies on the bond strength of adhesive systems to
      Nd:YAG irradiated teeth have shown distinctive behaviors when irradiation was
      applied before or after the adhesive agent. This study evaluated the microtensile
      bond strength of a commercial adhesive system to dentin irradiated with Nd:YAG
      laser after adhesive application but prior to polymerization. The experiment was
      conducted in vitro, using freshly extracted human teeth as samples. For the
      microtensile test, the teeth were separated into 4 different groups according to
      the energy density of laser irradiation: 0, 5, 10 and 50 J/cm2. The data was
      analyzed with analysis of variance (ANOVA) and LSD tests, and the results
      indicated that the group that was irradiated with 5 J/cm2 had significantly
      higher bond strength values. Adhesive penetration on the etched dentin was
      observed by scanning electron microscopy, where the images showed better adhesive
      penetration on dentinal tubules after dentin irradiation with 5 J/cm2. Based on
      the results of this study, it is possible to conclude that irradiation of dentin
      with the Nd:YAG laser at low energy densities after application of the adhesive
      but prior to polymerization might be positive for the adhesive restorative
      process.

PMID- 17024951
TI  - Pulse-delay curing: influence of initial irradiance and delay time on shrinkage
      stress and microhardness of restorative composites.
AB  - OBJECTIVES: Evaluate the influence of pulse-delay curing on shrinkage stress and
      microhardness of 2 restorative composites (Herculite XRV and Tetric Ceram).
      METHODS: Two pulse irradiances (500 and 100 mW/cm2) were applied for 1 or 5
      seconds, respectively (radiant exposure = 0.5 J/cm2). In both cases,
      photoactivation was completed applying 500 mW/cm2 for 39 seconds after a delay
      time of 0, 1 or 3 minutes. Shrinkage stress was monitored for 10 minutes in
      specimens 5-mm in diameter by 1-mm in height. Knoop hardness (KHN) was used to
      estimate the degree of conversion 10 minutes after photoactivation and after 48
      hours of storage in distilled water (37 degrees C) in specimens with similar
      geometry and dimensions. Additional KHN readings after 4 8 hoursof storage in
      ethanol (37 degrees C) were used to estimate polymer structure. The results were
      evaluated using ANOVA/Tukey test and Student t-test (a=0.05). RESULTS: For Tetric
      Ceram, 3-minute delay led to stress reduction compared to continuous curing at
      500 mW/cm2 (4.7+/-0.6 MPa and 7.0+/-1.3 MPa, respectively). At 100 mW/cm2, 1
      minute delay was enough to cause significant stress reduction (5.2+/-0.5 MPa).
      For Herculite, the pulse with 3 minute delay led to stress reduction compared to
      no delay for both irradiances (100 mW/cm2: 6.3+/-0.5 MPa and 7.8+/-0.8 MPa,
      respectively; 500 mW/cm2: 6.4+/-0.3 MPa and 7.8+/-0.7 MPa, respectively). At 10
      minutes, only small differences in microhardness were observed for both
      materials. No differences were found after water and ethanol storage (p>0.05).
      CONCLUSIONS: The composites behaved differently when subjected to pulse curing.
      Stress reduction was influenced by delay time but not by pulse irradiance. KHN
      results suggest that similar degrees of conversion and polymer structure were
      achieved with the photoactivation methods tested.

PMID- 17024952
TI  - Effect of thermal cycling on enamel bond strength of single-step self-etch
      systems.
AB  - This study investigated the influence of thermal cycling on the enamel bond
      strength of single-step self-etch adhesive systems. The systems used were
      Absolute, Clearfil tri-S Bond, G-Bond and One-Up Bond F Plus. Bovine mandibular
      incisors were mounted in self-curing resin, and the facial surfaces were wet
      ground with #600 SiC paper. Adhesives were applied on the prepared enamel
      surfaces and light irradiated according to each manufacturer's instructions.
      Resin composites were condensed into a mold (o4x2 mm) and light irradiated for 30
      seconds. Thirty specimens per adhesive systems were divided into 1 of 3 test
      groups (n=10) following storage in water at 37 degrees C for 24 hours. The
      specimens were then stored in 37 degrees C water for 24 hours, followed by
      thermal cycling 10,000 and 20,000 times between 5 degrees C and 60 degrees C.
      After each storage condition, the specimens were tested in shear mode at a
      crosshead speed of 1.0-mm/minute. One-way ANOVAs and Tukey HSD test at a level of
      0.05 were conducted. After 24 hours of water storage, the mean enamel bond
      strengths ranged from 11.3 to 16.9 MPa, and Clearfil tri-S Bond showed
      significantly higher bond strength. After thermal cycling, the mean bond
      strengths ranged from 8.3 to 20.7 MPa. The changes in enamel bond strengths were
      different among the adhesive systems tested. Failure modes after the test were
      commonly adhesive failure associated with partial cohesive failure adhesive in
      resin. With a careful choice of adhesive systems, the benefit to using single
      step self-etch systems in terms of simplifying the clinical procedure might be
      acceptable, even after thermal stresses.

PMID- 17024953
TI  - Surface hardness of resin composites after staining and bleaching.
AB  - This study investigated the effect of 3 staining solutions and 3 over-the-counter
      tooth-bleaching systems on the microhardness of 2 dental resin composites. Forty
      five specimens of Filtek Supreme and Esthet-X were randomly assigned to 3 groups.
      Over a 40-day test period, the specimens in each group (n=15) were immersed in 1
      of the 2 staining solutions (coffee and red wine) or distilled water as the
      control for 3 hours a day at room temperature. The 15 specimens in each staining
      group were further randomly divided into 3 subgroups, and the specimens in each
      subgroup (n=5) were bleached using one of the bleaching agents (Night Effects,
      Simply White Night and Opalescence Quick). Surface hardness was measured at 24
      hours after polymerization (baseline), after staining and after bleaching. Means
      and standard deviations were calculated, and the data were analyzed using
      repeated-measures analysis of variance and Duncan's Test. The microhardness of
      Esthet-X was significantly higher than Filtek Supreme at baseline (p<0.01). All
      specimens of both materials immersed in coffee and wine revealed a significant
      hardness decrease compared to baseline values (p<0.05). In the control group,
      microhardness was increased, and this increase was statistically significant for
      Filtek Supreme (p<0.05). After bleaching, there was a significant decrease in
      mean microhardness for all groups tested (p<0.05). No significant difference was
      found among bleaching agents.

PMID- 17024954
TI  - [The acerola fruit: composition, productive characteristics and economic
      importance].
AB  - The acerola (Malpighia emarginata Sesse y Mocino ex DC) is a wild plant grown in
      zones of tropical and subtropical climate. Acerola is origin from South of
      Mexico, Central America and Septentrional area of South America. Its scientific
      name was adopted in 1986 by the International Council of Vegetable Genetic
      Resources. Malpighia emarginata has a subglobulose drupa fruit with three seeds
      which account between the 19 - 25% of the total weight. The diameter and weight
      of the fruit varies between 1 - 4 cm and 2 - 15 g, respectively. The fruit shows
      green color when it is developing, which changes to yellow and red tones when it
      is mature. Each plant produces annually 20 - 30 kg of fruits. This fruit contents
      macro and micronutrients: proteins (0.21-0.80 g/100 g), fats (0.23-0.80 g/100 g),
      carbohydrates (3.6-7.80 g/100 g), mineral salts (iron 0.24, calcium 11.7,
      phosphorus 17.1 mg/100 g) and vitamins (thiamine 0.02, riboflavine 0.07,
      piridoxine 8.7 mg/100 g). Its high content in vitamin C (695 a 4827 mg/100 g) is
      remarkable, therefore acerola has an increasing economic value by its great
      consume during last years. Acerola also presents carotenoids and bioflavonoids
      which provide important nutritive value and its potential use as antioxidant.
      Brazil has a climate and soil appropriate for the culture of acerola, thus this
      country is the main mundial productor. Acerola is commercialised as juices, jams,
      ices, gelatins, sweets or liquors. Bibliographical data have been mainly supplied
      by Electronic Resources of the University of Seville and the University do Vale
      do Itajai (Santa Catarina, Brazil).

PMID- 17024955
TI  - [Review of the different methods for the evaluation of the in vitro antioxidant
      activity of wine and study of in vivo effects].
AB  - The aim of this paper is to evaluate the significance of these methods, as well
      as to correlate the antioxidant activity of wines with their phenolic profile,
      both in qualitative and quantitative terms. Red wines show higher antioxidant
      capacities than white ones and the magnitude of these differences depends on the
      method used. The antioxidant activity of wine can not be mainly ascribed to a
      particular phenolic compound, instead it is explained by the global interaction
      of all of them. To evaluate the influence of red wine consumption in the human
      organism, plasma antioxidant capacity has been frequently used as biomarker, and
      studies have shown that it increases after wine ingestion. We can conclude that
      it is necessary to use a battery of methods that provide different and
      complementary information to properly interpret the results. Phenolic compounds
      undergo metabolic transformations in the organism which modify their activities.
      In vivo assays do consider these changes. From the studies performed up to date
      we can conclude that acute ingestion of wine directly acts on plasma antioxidant
      capacity due to phenolic compounds and indirectly influences by means of changes
      on plasmatic concentration of endogenous antioxidants.

PMID- 17024956
TI  - [Conjugated linoleic acid (CLA) and its relationship with cardiovascular disease
      and associated risk factors].
AB  - The term CLA (conjugated linoleic acid) corresponds to a mixture of positional
      and geometric isomers of linoleic acid, of which two (9/c/, 11/t/ and 10/t/,
      12/c/) have biological activity. This review covers aspects related to CLA
      (sources, synthesis, distribution in human tissues, physiological activity), as
      well as its relationship with cardiovascular diseases. Most studies attribute the
      beneficial effects associated to the consumption of CLA to the reduction of risk
      factors for the development of cardiovascular diseases, such as the reduction of
      plasmatic triacylglycerols and cholesterol. Other research demonstrates the
      reduction of atherosclerotic processes. However, many studies indicate that CLA
      does not present beneficial effects or may even present negative effects. Thus,
      although there are a great number of studies related to CLA, we consider it
      premature to make any recommendation for the ingestion of these compounds, apart
      from those naturally present in a healthy diet.

PMID- 17024957
TI  - [Vitamin B12 and folate in non-institutionalized urban older people].
AB  - Vitamin B12 and folate deficiencies are the main nutritional determinants of
      hyperhomocysteinemia, which is an independent risk factor for cardiovascular
      diseases. There is scarce information about nutritional status on vitamin B12 and
      serum levels of folate in Mexican older people. The objective was to evaluate the
      nutritional status of vitamin B12 and folic acid concentration in non
      institutionalized, urban elderly men and women subjects. One hundred volunteers
      over 60 years were included in this cross-sectional study. Serum levels of
      vitamin B12 and folate were measured. In addition some biochemical and
      anthropometric indicators were also evaluated. Considering serum values of
      vitamin, 30% had vitamin B12 deficiency, 52% normal status and 18% with high
      levels. None subjects had folic acid deficiency, by the contrary, a high
      proportion (62%) showed elevated levels in serum. There was an effect of sex on
      vitamin B12 status. Elderly men showed significantly lower levels of vitamin B12,
      and it was according with significant higher prevalence of vitamin B12 deficiency
      in this group as compared with the women group. The high proportion of vitamin
      B12 deficiency found in this study underline a possible public health problem and
      guarantee further survey-studies about vitamin B12 status and to explore causes
      and consequences of the deficiency. Finally, due the sample size and the design
      of the study, the results must be seen with caution and not try to generalize.

PMID- 17024958
TI  - [Body mass index in a group of Venezuelan pregnant women and its relationship
      with the newborns' anthropometry].
AB  - To assess the relationship between maternal body mass index (BMI) at early
      gestation and the newborns' anthropometry, 105 mother-infant dyads from a public
      Maternity Hospital in Valencia Venezuela, were studied during 1998-2000. Weight
      and height of adult women between 10 and 15 weeks of gestation were used to
      calculate BMI according to Atalah's reference (Low weight, Normal, Over weight).
      Term newborns were assessed using gestational age calculated according to the
      Capurro method. Their weight, height, and head circumference were recorded, and
      were characterized using a Venezuelan reference. Newborns whose birth weight (BW)
      was pound 10th percentile were considered "small for gestational age" (SGA), and
      those with BW (3) 90th percentile as "large for gestational age" (LGA). One-way
      ANOVA and Tukey's Post Hoc test were used for group comparisons. There were 41.9%
      of "low weight" mothers, and 13.4% of SGA newborns. There were differences in the
      newborns' weight and height according to "Low weight" maternal BMI with "Normal"
      and "Over weight" maternal BMI (p < 0.05). A high prevalence of nutritional
      deficit was observed from the beginning of the gestational period, as well as a
      relationship between maternal BMI and the newborn's anthropometry.

PMID- 17024959
TI  - [Effect of a novel soy fermented product enriched with isoflavones and calcium on
      bone tissue of rats].
AB  - The objective was to evaluate the effect of soy fermented product intake on the
      corporal weight and bone tissue of ovariectomized mature rats. This product was
      fermented with Enterococcus faecium and Lactobacillus jugurti and enriched with
      isoflavones and calcium. The animals were divided in 5 groups: sham
      ovariectomized; ovariectomized; ovariectomized treated with soy fermented product
      enriched with isoflavones and calcium; ovariectomized treated with soy fermented
      product enriched with calcium and ovariectomized treated with non-fermented
      product enriched only with calcium. In order to evaluate the effect of the tested
      product on bone tissue (femur and tibia), the following parameters were analyzed:
      length; mechanical assay of three points; density (Archimedes principle); mineral
      content; calcium content; measure of the trabecular widths. The corporal weight
      of group treated with soy fermented product containing isoflavones and calcium
      showed no statistical difference from sham-ovariectomized group and trabecular
      widths tended to have larger than ovariectomized group. However, there was no
      significant difference to the other evaluated parameters in result of the diverse
      treatments. Thus, soy fermented product enriched with isoflavones and calcium
      inhibited the increasing of corporal weight caused by ovariectomy and revealed a
      tendency to trabecular protection after castration.

PMID- 17024960
TI  - [Contribution of Semiology for Nutritional Diagnosis of Hospitalized Patients].

PMID- 17024961
TI  - [The menarche age in teenagers of the Northwest of Mexico].
AB  - The beginning of sexual maturity in individuals is a measure commonly used as an
      indicator of a population's quality of life. Among women, one of the most
      frequently used indicators is the age of menarche. The objectives of this
      research were to obtain the age of menarche in school age girls from the
      Northwest of Mexico, and to establish the relationship between the latter with
      their socioeconomic level, body weight, and height. The sample was taken from 857
      girls between 7 and 17 years old from different socioeconomic level sectors. The
      age of menarche of these girls was determined by the statu quo method. The value
      found for menarche was 12.06 +/- 0.44 years old. We also found an association of
      menarche to height (p < 0.01) and to socioeconomic level (p < 0.01). The value
      for age of menarche in this study was similar to the one reported for other Latin
      American populations. Taking into consideration that approximately 70% of the
      Mexican population has been considered of low income level and that the
      environmental conditions are not entirely favorable, it is possible that this
      could be the result of genetic and environmental interactions.

PMID- 17024962
TI  - [Dietary patterns and its relation with overweight and obesity in Chilean girls
      of medium-high socioeconomic level].
AB  - The aim of the present study was to identify dietary patterns in girls and to
      assess their association with obesity or overweight. A school-based sample of 108
      girls between 8 and 11 years of medium-high socioeconomic level was selected in
      Santiago, Chile. The body mass index was calculated and a quantified food
      frequency and physical activity questionnaires (validated in the FAO/MINEDUC/INTA
      Project Nutritional Education in primary schools) were applied. Four distinct
      dietary factors or patterns were obtained explaining 54% of the total variation
      using factorial analysis. The first factor was characterized by an energy-dense
      diet (high consumption of fat foods, ice creams, chocolates, French fries,
      snacks). The second factor represented a healthy diet (dairy products, fruits and
      salads). The third factor represented intake of soft drinks (either with or
      without sugar). The fourth factor represented a diet rich in calories and sugars
      (bread, sausages, sweets). The association between the four dietary factors and
      overweight/obesity was assessed through logistic regression models. The first
      factor, energy-dense foods, was the only one significantly associated with the
      presence of obesity (OR = 1.86; 95% CI: 1.12 - 3.09). The results of this
      research about dietary patterns are consistent with studies carried out in other
      countries.

PMID- 17024963
TI  - [Comparison of the antibiotics sensibility pattern of Listeria monocytogenes and
      Salmonella spp. strains isolated from food with clinical origin samples].
AB  - The actual use of antibiotics includes, not just its therapeutic cases, but also
      for disease prevention and as a growth promoter in animals. These practices have
      resulted in the propagation of resistance to antibiotics, representing a threat
      for Public Health. In this work, the antibiotic sensibility pattern of 20
      Listeria monocytogenes and 40 Salmonella spp. strains, isolated from foodstuff
      was studied and compared with the antibiotic sensibility patterns of 20 L.
      monocytogenes and 100 Salmonella strains of clinical origin. 95% of the L.
      monocytogenes strains isolated from food were sensible to ampicillin, compared
      with the 65% of the clinical origin strains. Same way, 100% of food strains were
      sensible to gentamicin, compared with 85% of clinical origin strains. 95% of both
      showed sensibility to trimethoprim sulfametoxazole and 100% to ciprofloxacin. For
      Salmonella spp., the sensibility patterns for trimethoprim sulfametoxazole,
      gentamicin, ciprofloxacin, nalidixic acid and amoxicilin/clavulanic acid from
      both origins were similar. Nevertheless, food origin strains showed a 97.5% and
      82.5% sensibility for tetracycline and cephalosporin respectively, compared with
      a 83 and 90% sensibility shown by clinical origin strains. The results obtained
      demonstrate the potential risk that bacterial strains isolated from food
      represent in the transmission of antibiotics' resistance.

PMID- 17024964
TI  - [Effect of different cooking treatments of Mucuna beans on its L-Dopa content].
AB  - The main limiting factor in the consumption by humans of the velvet bean (Mucuna)
      is its relatively high content of L-Dihydroxyphenylalanine (L-Dopa), with levels
      as high as 9%. Conventional cooking methods used to transform raw velvet bean
      into an edible product are not sufficiently effective in reducing the levels of L
      Dopa in adequate processing time. In this report, Mucuna beans were cooked by
      microwave, utilizing vapor and in water solutions at pH 3, 6, 7, 9 and 11.
      Cooking alkaline solutions were achieved using sodium hydroxide, potassium
      hydroxide, and calcium hydroxide. The acid pH was achieved through the use of
      HCl. The initial cooking time was fixed at 6 hrs. The processed bean samples were
      dried, ground and analyzed for L-Dopa and protein. The ground samples were
      further washed with boiling water for 0, 3 and 6 minutes, them dried and
      analyzed. None of the procedures evaluated was capable of eliminating L-Dopa from
      Mucuna beans. The Ca(OH)2 treatment at pH 9 which was washed with hot water
      produce a reduction of L-Dopa of 80.4%. There was not effect attributed to the
      alkaline ions. Reducing particle size appears to be most effective as it has been
      shown by other workers.

PMID- 17024965
TI  - [Development of an optimized formulation of flaxseed (Linum usitatissimum)
      mousse].
AB  - Taguchi method was applied to determine the maximum sensory quality of a
      functional flaxseed mousse desert ready to mix by minimizing the deviation from
      the target value. An orthogonal array (OA) experimental design that allows to
      analize simultaneously the influence of four independent variables (thermic
      process; carrageen/gelatine ratio; grated cocconut/cocconut flavour ratio;
      whipping time) with three tolerance level each was applied to evaluate the
      effects of these control factors. Performance measure analysis were carried out
      using standard analysis to calculate average effects of factor levels and
      variance analysis, in order to determine the optimum levels and significant
      contribution of the control factors. To determine the optimum conditions,
      Taguchi's "the large the better" formula was used. These turn out to be thermic
      process, 95 degrees C/90s; carrageen/gelatine, 0.54g/ 1.07g; grated cocconut/
      cocconut flavour, 10.7g/4.23g; whipping time, 8 min. Sensory quality was
      determined using the composite scoring test and a trained sensory panel of 12
      judges. Chemical composition of optimized flaxseed mousse turn out to be protein,
      20%; total dietary fibre, 18%; carbohydrates, 26.7%. Omega 6/omega 3 ratio of 0.4
      was considered good. Amount of flaxseed in optimized flaxseed mousse was enough
      to satisfy the 30% of recommended dietary allowance of linolenic acid. Shelf life
      data showed a good stability for this product as well a good consumer
      acceptability.

PMID- 17024966
TI  - Colostrinin decreases spontaneous and induced mutation frequencies at the hprt
      locus in Chinese hamster V79 cells.
AB  - Colostrinin (CLN), a uniform mixture of low-molecular weight, proline-rich
      polypeptides, induces neurite outgrowth of pheochromocytoma cells, extends the
      lifespan of diploid fibroblast cells, inhibits beta amyloid-induced apoptosis and
      resulted in improved cognitive function when administered to Alzheimer's
      patients. Here we investigated CLN's antimutagenic activity in cells stressed
      oxidatively or exposed to chemical or physical agents. Our data show that CLN did
      not alter cell cycle kinetics and cloning efficiency, while it inhibited the
      development of spontaneous mutations at the coding region of the hypoxanthine
      phosphoribosyl-transferase (hprt) gene in Chinese hamster V79 cells. In a dose
      dependent manner, CLN lowered reactive oxygen species (ROS)-induced frequency of
      cells resistant to 6-thioguanine (6-TG) to nearly background level. Likewise, CLN
      decreased the frequency of methyl methanesulfonate- or mitomycin C-induced
      mutations in V79 cells. Notably, CLN (at 100, 250, and 500 ng per ml
      concentrations) decreased UVA-induced mutation frequency, while only the highest
      dose of CLN also decreased significantly the number of UVB-induced 6-TG-resistant
      mutant cells. Similar results were obtained using cell cultures of human origin.
      Overall, our data show that CLN significantly lowers the mutation frequency that
      develops spontaneously or is induced by ROS, chemical and physical agents. CLN
      itself has no mutagenic activity. Therefore, CLN may be used in human therapies
      systemically and/or locally for the prevention of diseases associated with
      sequence alterations in genomic and mitochondrial DNA.

PMID- 17024967
TI  - Potentiation of alkylating agents by NLCQ-1 or TPZ in vitro and in vivo.
AB  - PURPOSE: To investigate potential synergistic interactions between bioreductive
      agents, either NLCQ-1 or tirapazamine (TPZ) and two alkylating chemotherapeutic
      drugs, and how such interactions compare in vitro and in vivo. MATERIALS AND
      METHODS: V79 cells (in vitro studies) and the SCCVII/C3H murine tumor model (in
      vivo studies) were used. The alkylating chemotherapeutic agents examined were
      cisplatin (cisDDP) and melphalan (L-PAM). In vivo, all agents were administered
      by i.p. injection wherein NLCQ-1 and TPZ were given at equitoxic doses of 10 and
      23 mg/kg, respectively. Optimal administration schedules and dose modification
      factors (DMF) were determined in vivo for the antitumor effect or bone marrow
      toxicity by using the in vivo-in vitro clonogenic assay as the endpoint. RESULTS:
      A schedule-dependent synergistic interaction was observed between NLCQ-1/TPZ and
      each alkylating agent, both in vitro and in vivo, and an optimal potentiation was
      obtained when each bioreductive agent was administered prior to each
      chemotherapeutic drug. However, significant DMF values and an in vivo therapeutic
      index (TI) was obtained only with NLCQ-1. Limited mechanistic studies in V79
      cells by using the alkaline comet assay demonstrated that hypoxic preincubation
      with NLCQ-1 increases the cross-links induced by subsequent aerobic exposure to
      cisDDP. CONCLUSIONS: These results verify our previous observations in EMT6
      tumors and suggest a potential clinical use of NLCQ-1 as a synergistic adjuvant
      to chemotherapy with alkylating agents against solid tumors possessing hypoxic
      regions.

PMID- 17024968
TI  - Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti
      angiogenic agent.
AB  - Integrin alpha5beta1, the principal fibronectin receptor, is an important
      survival factor, playing a key role in angiogenesis. Angiogenesis is critical for
      tumor growth, and anti-angiogenic therapies have met clinical success. To
      validate the therapeutic potential of an anti-alpha5beta1 strategy, we generated
      volociximab (M200) a chimeric human IgG4 version of the alpha5beta1 function
      blocking murine antibody IIA1; and F200, the Fab derivative. Volociximab, F200
      and IIA1 showed similar activity by ELISA (EC50= 0.2nM), Biacore (Kd= 0.1-0.4nM)
      and inhibition of fibronectin binding (IC50= 2-3nM). The inhibitory potential of
      alpha5beta1 antibodies was compared to HuMV833, an anti-VEGF antibody. Both
      volociximab and HuMV833 inhibited HUVEC proliferation (IC50 of volociximab = 0.2
      0.5nM; IC50 of HuMV833 = 45nM). However, IIA1, volociximab and F200 were also
      potent inhibitors of an in vitro model of angiogenesis (HUVEC tube formation
      assay), unlike HuMV833. Additionally, volociximab inhibited in vitro tube
      formation induced by VEGF and/or bFGF, suggesting a mechanism of action
      independent of growth factor stimulus. In fact, inhibition of alpha5beta1
      function by volociximab induced apoptosis of actively proliferating, but not
      resting, endothelial cells. Volociximab does not cross-react with rodent
      alpha5beta1, therefore in vivo validation of an anti-alpha5beta1 approach was
      conducted in a cynomolgus model of choroidal revascularization. Volociximab and
      F200 were potent inhibitors of neovessel formation in this model. These data
      demonstrate that volociximab has therapeutic potential in diseases in which new
      vessel formation is a component of the pathology.

PMID- 17024969
TI  - Benzyl isothiocyanate (BITC) induces apoptosis in ovarian cancer cells in vitro.
AB  - Advanced ovarian cancer (OC) is not curable by surgery alone and chemotherapy is
      essential for its treatment. Isothiocyanates have been shown to inhibit
      carcinogen-induced tumorigenesis in animal models, yet no efforts have been made
      to determine their therapeutic potential in OC. In the present study, we
      investigated the mechanism of the anti-proliferative and apoptotic activity of
      benzyl isothiocyanate (BITC) in OC. BITC inhibited the proliferation of OC cells
      and induced apoptosis in OC cells. Apoptosis was induced by a strong activation
      of caspase-3 and -9, and cleavage of PARP-1. However, caspase-8 was not activated
      by BITC. Cytotoxic effects of BITC were reversed by the inhibition caspase-3 and 
      9 specific inhibitors. BITC showed a concentration dependent decrease in the
      levels of Bcl-2 with a concomitant increase in Bax levels. In addition, BITC
      activated proapoptotic signaling by phosphorylation JNK1/2 and p38 while
      simultaneously inhibiting survival signaling mediated by ERK1/2 and Akt
      phosphorylation in a dose-dependent manner. While JNK inhibitor SP600125 and p38
      inhibitor SB203580, abolished the cytotoxic effect of BITC, MEK inhibitor,
      PD98059 and PI3 kinase inhibitor, LY294002 failed to show such reversal
      indicating a critical role played by JNK1/2 and p38 signaling in apoptosis
      induced by BITC. In summary, our studies demonstrate that BITC inhibits
      proliferation of OC cells and induces apoptosis via caspase-9 and -3 pathways.
      BITC inhibits ERK1/2 and Akt survival signaling while simultaneously activating
      pro-apoptotic p38 and JNK1/2. Therefore, BITC can be potentially developed as a
      therapeutic agent to treat OC.

PMID- 17024970
TI  - Effects of perillyl alcohol and heat shock treatment in gene expression of human
      lung adenocarcinoma cell line A549.
AB  - The K-Ras protein is found mutated in 42.4% of lung adenocarcinoma cases,
      evidencing its importance as a chemotherapeutic target. The Ras protein becomes
      functional after farnesylation, a post-transduction modification, allowing its
      attachment to the cellular membrane permitting signal transduction. Perillyl
      alcohol (POH) has been shown to inhibit the farnesylation of small G-proteins
      such as Ras. HSP70, a protein known to appear after heat shock (HS), is found
      over expressed in lung cancer and modifies chemotherapeutic effects. In this
      work, the effect of POH and HS in the gene expression of human adenocarcinoma
      lung cells (A549) is studied. Cells incubated with POH followed by 42 degrees C
      HS presented a 20.7% cellular viability decrease compared to the ones kept at 37
      degrees C. A different pattern synthesis was observed for each sequences of cell
      treatment. Independent of the heat treatment, the amount of HSP70 was decrease by
      POH without modification in the amount of p53. Here it is shown that HS modified
      the POH effects in the ERK activation pathway by altering the phosphorylation of
      p44/42 in human adenocarcinoma lung cells.

PMID- 17024971
TI  - Chemopreventive activity of a macrofungus Phellinus rimosus against N
      nitrosodiethylamine induced hepatocellular carcinoma in rat.
AB  - Chemoprevention is an important alternative approach to control cancer. Chemical
      substances with multiple inhibitory properties would be a welcome addition to the
      class of chemopreventive drugs. In this study, we investigated the antioxidant,
      anti-inflammatory, antimutagenic and cancer preventive activities of aqueous
      extract of a macrofungus Phellinus rimosus (Berk) Pilat. The extract exhibited
      superoxide anion (O2-), hydroxyl radical (*OH), nitric oxide (NO*) scavenging and
      lipid peroxidation inhibiting activities. The inhibitory concentrations required
      by the extract to scavenge 50% (IC50) of the superoxide anion, hydroxyl radical
      and nitric oxide generated were 126 +/- 5.1, 71 +/- 4.7 and 31 +/- 4.5 microg/ml
      respectively. The concentration required to inhibit 50% of Fe2+ induced lipid
      peroxidation in rat liver homogenate was 318 +/- 2.4 microg/ml. The extract
      showed significant (P<0.05) anti-inflammatory activity in a dose dependent
      manner. Extract (100 mg/kg body wt, p.o) inhibited 44.5, 45.4 and 47%
      carrageenen, dextran and formalin induced inflammations respectively. The
      antimutagenic activity was determined by the Ames' Salmonella mutagenecity assay
      using histidine mutant Salmonella typhimurium strains. The extract at
      concentration of 5 mg/plate showed antimutagenecity against benzo[a]pyrene
      (B[a]P) and 4-nitro-o-pheneylenediamine (NPDA) induced mutations of TA98 and
      TA100 respectively. Anticarcinogenic activity was evaluated using N
      nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC) in rats. Serum
      gamma glutamyl transpeptidase (GGT), glutamate oxaloacetate transaminase (GOT),
      glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) activities
      and lipid peroxidation level (MDA) were elevated significantly (P<0.05) in the
      NDEA alone treated group of animals. Treatment of the extract (25 and 50 mg/kg
      body wt, p.o.) prior to the NDEA administration decreased the serum GGT, GOT, GPT
      and ALP activities and MDA level in a dose dependent manner. The NDEA alone
      treated animals showed altered serum albumin/globulin ratio (A:G ratio),
      hyperfibrinogenaemia, increased hepatic glutathione S-transferase (GST) activity,
      glutathione-peroxidsae (GPx) activity and reduced glutathione (GSH) level
      compared to the extract plus NDEA treated group. The extract also inhibited in
      vitro aniline hydroxylase (AH) activity of rat liver induced by phenobarbitone in
      a dose dependent manner. The results, thus suggest the significant
      chemopreventive properties of the aqueous extract of the Phellinus rimosus
      against NDEA induced hepatocellular carcinoma by its antioxidant, anti
      inflammatory and antimutagenic activities.

PMID- 17024972
TI  - Cholecalciferol (vitamin D3) and the retinoid N-(4-hydroxyphenyl)retinamide (4
      HPR) are synergistic for chemoprevention of prostate cancer.
AB  - Prostate cancer, the most commonly diagnosed cancer among American men, develops
      slowly over many years. The long latent period of 20 to 30 years, involved in the
      multistep process of carcinogenesis, provides an important opportunity to block
      or reverse progression to a malignant state. Vitamin A (retinoids) and vitamin D
      not only have the ability to block steps in the process of carcinogenesis but
      they can also modulate or reverse some malignant characteristics of cancer cells.
      However, at high levels, vitamins A and D have undesirable side effects, thus,
      limiting effective dose levels and efficacy. Therefore, combination treatment at
      low doses, to increase efficacy and avoid toxicity, is of special interest. This
      study examines the effects of the synthetic retinoid N-(4
      hydroxyphenyl)retinamide (4-HPR) in combination with cholecalciferol (vitamin D3)
      on growth, and on the expression of vimentin, matrix metalloproteinase-2 (MMP-2),
      and retinoid and vitamin D receptor expression, using the non-tumorigenic, human
      prostate epithelial cell line RWPE-1. Treatment with 4-HPR and cholecalciferol
      resulted in synergistic growth inhibition when compared to that caused by each
      agent alone. A decrease in vimentin expression and MMP-2 activity, and up
      regulation of vitamin D receptor (VDR) and some of the retinoid-X (RXRs) and
      retinoic acid receptor (RARs) subtypes, was observed. These results suggest that
      combined treatment with 4-HPR and cholecalciferol, at doses lower than what might
      be effective with single agents, increases their efficacy and suggest that this
      may serve as an effective strategy for chemoprevention and treatment of prostate
      cancer.

PMID- 17024973
TI  - [Veterinary medicine, "Bolognese type"?].

PMID- 17024974
TI  - [Travel medicine of parasitic diseases in the dog].
AB  - Companion animals are increasingly brought along by their owners to foreign
      countries. Thus, small animal travel medicine is becoming more important. The
      field includes both prophylaxis and metaphylaxis against various infectious
      diseases, as well as their diagnosis and treatment. Dogs returning from Southern
      Europe, but also from more tropical regions, may be infected with exotic
      pathogens. In addition, imported pedigree or working dogs, and especially stray
      dogs imported through welfare organisations, are at high risk. The present
      overview summarises the clinical and practical aspects of exotic parasitic
      diseases that may affect such dogs, and the risk of such diseases becoming
      autochthonously transmitted in Switzerland. Furthermore, the zoonotic potential
      of these infections will be considered.

PMID- 17024975
TI  - [Methods for investigating Trichinella infections in domestic and wild animals].
AB  - Trichinellosis is an important parasitic zoonosis that is caused by the
      intracellular nematode Trichinella spp.. Infection of humans occurs through
      consumption of raw (or undercooked) meat containing infectious larvae. In Europe,
      meat from pork, horse, and wild boar have been identified as most important
      sources of Trichinella infections in humans. In Switzerland, both the domestic
      pig and wild boar population are considered free of Trichinella. Conversely,
      Swiss foxes, lynxs and recently a wolf were found to be infected, the species
      identified in these animals was always referred to as Trichinella britovi.
      Although this species rarely infects pork and, compared to Trichinella spiralis,
      only causes reduced pathogenic effects in humans, the basic presence of
      Trichinella in Switzerland cannot be neglegted. This fact has gained increasing
      importance since the responsible authorities in the European Union (EU) are
      preparing regulations for the official Trichinella-control in meat in order to
      improve food safety for consumers. These regulations will be implemented as a
      consequence of the recent association of east European countries with the EU.
      This new legislation particularly takes into account, that in the past by far
      most cases of human trichinellosis in the EU were due to consumption of imported
      east European meat.Within the framework of the bilateral agreements of
      Switzerland with the EU, the Swiss veterinary public health authorities will have
      to comply with the foreseen EU regulations. Although diagnostic methods for the
      direct demonstation of Trichinella in pork meat are already routine practice in
      several Swiss abattoirs, the implementation of a meat control program for
      Trichinella for the entire slaughter pig population of the country would lead to
      an enormous increase in costs for the administration and will require an
      increased infrastructure in veterinary services. In order to find a reduced
      testing format for monitoring Trichinella infections in Swiss pork, an infection
      risk-oriented survey strategy is currently evaluated. In the present article,
      this minimized survey strategy is discussed regarding its compatibility with the
      EU regulations laying down rules for the official control of meat for
      Trichinella.

PMID- 17024976
TI  - The use of light- and electron microscopy for studies on the cell- and molecular
      biology of parasites and parasitic diseases.
AB  - Lightmicroscopical (LM) and electron microscopi cal (EM) techniques, have had a
      major influence on the development and direction of cell biology, and
      particularly also on the investigation of complex host-parasite relationships.
      Earlier, microscopy has been rather descriptive, but new technical and scientific
      advances have changed the situation. Microscopy has now become analytical,
      quantitative and three-dimensional, with greater emphasis on analysis of live
      cells with fluorescent markers. The new or improved techniques that have become
      available include immunocytochemistry using immunogold labeling techniques or
      fluorescent probes, cryopreservation and cryosectioning, in situ hybridization,
      fluorescent reporters for subcellular localization, micro-analytical methods for
      elemental distribution, confocal laser scanning microscopy, scanning tunneling
      microscopy and live-imaging. Taken together, these tools are providing both
      researchers and students with a novel and multidimensional view of the intricate
      biological processes during parasite development in the host.

PMID- 17024977
TI  - [Search for Neospora caninum DNA in bull semen using PCR ].
AB  - Neospora caninum represents one of the most frequent abortifaciant organisms
      worldwide. The parasite is diaplacentally transmitted from the pregnant cow to
      the fetus, where it normally leads to the delivery of a healthy, however
      persistently infected calf. Abortion thus is a relative rare event. The
      transmission of bovine neosporosis occurs in more than 90% of the cases
      vertically due to the endogenous reactivation of a persistently infected mother.
      Exogenous infections are therefore responsible for less than 10% of the cases.
      The question arises about which infection sources may be relevant in this
      context. In Switzerland, the role of dogs as definitive hosts has been shown to
      be of low significance in that respect. Recently, discussion focused on the
      potential of infectious bull semen following natural or artificial insemination.
      Thus, a few years ago a report documented the detectability of N. caninum-DNA in
      the semen of naturally infected bulls by nested-PCR. As a consequence, we decided
      to gain own experience by investigating 5 separate semen specimens per animal,
      originating from 20 N. caninum-seropositive bulls used for artificial
      insemination in Switzerland. All probes turned out to be negative by nested PCR.
      Based upon our laboratory experiences, the potential bull semen-associated
      Neospora-problem seems not to affect the Swiss bull population, thus there is no
      evidence to include further respective means of control.

PMID- 17024978
TI  - [Imported coenurosis in sheep].
AB  - Thirteen sheep from a milk producing farm in the Canton of Grisons that presented
      chronic coenurosis were examined and subjected to treatment trials at the
      veterinary hospital in Zurich. Symptoms were first observed around two months
      after the import of two dogs from Italy (Abruzza) of which one was infected with
      Taenia multiceps and Echinococcus granulosus. The most frequently observed
      clinical symptoms of the sheep were reduced general condition, circling, reduced
      menace reflex, apathy, unsteady gait and head tilt. Analyses of cerebrospinal
      fluid revealed an increased leucocyte count in 3 sheep and eosinophilia in 4
      sheep. In 4 animals that underwent computertomography, one or more hypodense,
      definable lesions were found in the brain. In 2 sheep surgical treatment and in
      10 animals medical treatment with either Praziquantel (n=8) or Oxfendazol (n=2)
      was attempted. Only one animal treated with Praziquantel needed not to be
      euthanized. At necropsy, one or two coenurus cysts could be found either in a
      side ventricle (n=2), in the cerebellum (n=3) or in the cerebrum (n=7). The
      locations corresponded with the clinical findings. Despite Praziquantel or
      Oxfendazol treatment, living protoscoleces could be found in the parasite cysts.

PMID- 17024979
TI  - [Echinococcus multilocularis in Grisons: distribution in foxes and presence of
      potential intermediate hosts].
AB  - The southern border of the European endemic area of Echinococcus multilocularis
      runs along the alpine crest. This endemic transition area was analysed in the
      canton Grisons on a small spatial scale. A total of 543 foxes originating from 10
      areas north and 4 areas south of the main alpine divide were investigated.
      Parasites were isolated using the sedimentation and counting technique on
      intestinal contents. The mean prevalence of E. multilocularis was 6.4% with
      significant differences between different areas. In the southern valleys, only
      foxes from the Val Mustair were infected (14.3%). On the northern side of the
      main alpine divide, prevalences varied between 0 and 40%. The predation habits of
      foxes on potential intermediate hosts was investigated by means of stomach
      content analyses (n=530). Rodents of the genera Microtus/Pitymys were found in
      19.6% of fox stomachs, Clethrionomys glareolus in 8.0% and Arvicola terrestris in
      0.4%. A small scale analysis based on a 10 x 10 km grid suggested that the
      predation rate on the genera Microtus/Pitymys significantly correlated with the
      prevalence of E. multilocularis in foxes (Spearman's r = 0.51). Hence, E.
      multilocularis appears to occur in the alpine study area on a very small spatial
      scale. These local sources of infection may persist for decades. This may partly
      explains why, during the last 34 years, some human cases of alveolar
      echinococcosis occurred in areas of the Canton Grisons where the parasite is
      presently endemic in foxes. No such human cases have been recorded in other areas
      free of E. multilocularis.

PMID- 17024980
TI  - [Overview of helminth problems in domestic ruminants in Switzerland].
AB  - Potent anthelmintics were introduced into the Swiss market several decades ago.
      Despite this, gastrointestinal nematodes (GIN), lungworms and the large liver
      fluke (Fasciola hepatica) can successfully inhabit Swiss ruminant farms. This is
      mainly due to a high reproductive capacity as well as very efficient survival
      strategies. In addition some species readily develop anthelmintic resistance. GIN
      infections in young cattle are under comparatively good control. However,
      prophylactic measures are compromised where adult stock is also affected due to
      incomplete development of immune protection. Under these circumstances control
      measures must include all age groups. This results in fewer helminths in refugia
      thus may accelerate the development of anthelmintic resistance. This review aims
      to present a synopsis of the significance of the major helminth infections
      obtained on pasture by large and small ruminants in Switzerland. Currently
      available strategies for strategic helminth control are summarized and an outlook
      is given on new developments which might expand the spectrum of control measures
      relevant for veterinary practice in the future.

PMID- 17024981
TI  - Cyclic loading of endodontically treated teeth restored with glass fibre and
      titanium alloy posts: fracture resistance and failure modes.
AB  - The aims of this in-vitro investigation were to compare the fracture resistance
      and the failure modes of endodontically treated teeth restored with glass fibre
      reinforced posts with those of teeth restored with titanium-alloy posts. A total
      of 60 single-rooted human mandibular premolars were endodontically treated. The
      teeth were divided into two experimental and one control group. Post spaces 9mm
      long were prepared in the roots of the experimental groups in which glass fibre
      reinforced posts (Group A) and titanium-alloy posts (Group B) were cemented. In
      the control group (Group C), no post was inserted. The specimens were stored in
      normal saline for a period of three weeks before being intermittently loaded at
      an angle of 30 degrees degrees to the long axis of the tooth at a frequency of
      two loads of 40N per second. Log-rank test used for the overall analysis revealed
      that there was no significant difference of fracture resistance between teeth
      restored with glass fibre-reinforced posts (Group A) and titanium-alloy posts
      (Group B). The survival of the control group was found to be significantly
      inferior to that of the experimental groups. There was no significant difference
      in the number of failures between the two experimental groups. There was
      significantly more core and post failure for the glass fibre-reinforced posts,
      root and core failure for the titanium-alloy posts and core failure for the
      control group. The results suggest that post failures are more frequent in teeth
      restored with quartz fibre posts and root fractures are more frequent in teeth
      restored with titanium posts.

PMID- 17024982
TI  - Specialisation and specialist education in prosthetic dentistry in Europe.
AB  - This presentation reports on the results of a meeting of prosthodontists from
      selected European countries. The aim of the meeting was to analyse and promote
      specialisation and specialist education in Prosthetic Dentistry in Europe.
      Representatives for Europe were selected from the European Prosthodontic
      Association (EPA) board, the Education and Research Committee of International
      College of Prosthodontists (ICP), countries with a legally recognised speciality,
      countries without a recognised speciality but organised training programmes and
      countries with neither of these situations. Data about specialisation and
      specialist training in Prosthodontics in Europe was scrutinised and discussed.
      The programmes for countries with specialist training had relatively similar
      content, mostly of three years duration. There was strong agreement that a
      recognised speciality raises the level of care within the discipline for both
      specialists and non-specialists. In several of the countries where a speciality
      had been introduced it had been initiated by pressure from public health planning
      authorities. The conclusions are that from a professional viewpoint an
      advancement of the speciality over Europe would develop the discipline, improve
      oral health planning and quality of patient care. A working group for
      harmonisation was recommended.

PMID- 17024983
TI  - Assessment of the oral health related quality of life of patients awaiting
      initial prosthetic assessment.
AB  - The aim of the study was to quantify the impact of oral health problems on the
      quality of life of patients who were experiencing difficulties with dentures. Two
      hundred and ten patients who were awaiting an initial specialist assessment
      appointment were asked to complete the short form Oral Health Impact Profile
      (OHIP-14). One hundred and sixty three (78%) questionnaires were completed
      correctly and were analyzed. Overall, the prevalence of impacts was high in all
      sub-scales, indicating that denture related problems had a negative impact on
      quality of life of both partially dentate and elderly patients.

PMID- 17024984
TI  - The investigation of solubility values,water sorption and bond strength of auto
      polymerising and heat-polymerising acrylic resin materials.
AB  - In this study the solubility, water sorption and the bond strength of auto
      polymerising and heat-polymerising acrylic resins were investigated. Two auto
      polymerising and five heat polymerising acrylic resin materials were used for
      this study. Thirty-five specimens were prepared (50 mm in diameter and 0.5 +/-
      0.01 in thickness) for water sorption and solubility tests. In order to examine
      bond strength, specimens were prepared in 2.5 x 10 x 64 mm dimensions. These
      specimens were repaired with QC and major repair acrylic. Some specimens were
      kept in distilled water for 50 hours, and others for 30 days. The strength of the
      bond was measured by a Pull-Compress device. As a result of the variance
      analysis; water sorption, solubility and the bond strength between acrylic resins
      were identified as statistically significant (P < 0.001). The water sorption of
      the major acrylic resin specimens were lower than the other materials (P <
      0.001).

PMID- 17024985
TI  - Effect of five staining solutions on the colour stability of two acrylics and
      three composite resins based provisional restorations.
AB  - The effect of coffee, tea, coca-cola, orange-juice and red wine on the colour
      stability of acrylic and composite based provisional materials were evaluated.
      Two acrylic resins and three composite resins were studied. 48 standardized
      specimens for each provisional material were prepared. Each group was divided
      into 6 subgroups. Specimens from each group were immersed in staining solutions
      at room temperature for 30 days. Red wine and tea caused the most significant
      colour changes and orange juice showed the least significant colour changes.
      deltaE of all of the provisional restorations materials was changed after the
      immersion in all of the staining solutions during the experimental process.

PMID- 17024986
TI  - Monitoring recruitment success and cost in a randomized clinical trial.
AB  - Recruitment of older adults into research studies is challenging and, as a
      consequence, the recruitment period is often extended and more expensive than
      planned. This study monitored the effectiveness (number of subjects attracted)
      and cost of different recruitment strategies when recruiting edentulous elderly
      adults. Socio-demographic data were gathered and compared to 2001 Canadian census
      data. Advertisements in major Montreal newspapers attracted the most people
      (24.3%). However, the most economical recruitment method proved to be placement
      of ads in senior newspapers (dollar 73.74 per subject). The information gathered
      in this study will assist others in planning recruitment strategies for
      edentulous elderly populations.

PMID- 17024987
TI  - The effect of colour defective vision on shade matching accuracy.
AB  - One hundred and forty one male dental students and staff were screened for colour
      defective vision. Ten colour-defective and 20 non colour-defective subjects then
      carried out a shade matching exercise using nine selected shades and another
      matched, shade tab (to test for consistency) from Vita shade guides. All shade
      matching took place under standard lighting conditions. Each subject also
      completed a short questionnaire relevant to shade matching. There were no
      significant differences found between colour-defective and non colour-defective
      subjects in shade matching abilities. Although both subject groups were similar
      in their shade matching abilities, individuals with colour defective vision
      perceived it to be a slightly more difficult exercise.

PMID- 17024992
TI  - [Risk behaviors in seropositive patients: prevention, now and always!].

PMID- 17024993
TI  - [Insulin requirements during pregnancy].

PMID- 17024994
TI  - [Emergencies and nurse education in basic life support care].

PMID- 17024995
TI  - [Leonetti Law, care and end of life. Rights, liberties and end of life].

PMID- 17024996
TI  - [The end of life, a life experience of liberty and dignity].

PMID- 17024997
TI  - [Leonetti Law of April 11, 2005, a law on the end of life].

PMID- 17024998
TI  - [Patients' rights in the end of life, legal difficulties and practices to
      overcome].

PMID- 17024999
TI  - [The double effect, from a moral principle with to a legislative vision].

PMID- 17025000
TI  - [Nurse's role in drawing up advance directives].

PMID- 17025001
TI  - [Three essential dispositions in the Leonetti Law applied to neuroanesthesia
      resuscitation].

PMID- 17025002
TI  - [Support and terminal care of the elderly in the hospital, the experience of
      nurses].

PMID- 17025003
TI  - [Law on the end of life, informing and education home care nurses].

PMID- 17025004
TI  - [Leonetti Law, care and the end of life].

PMID- 17025005
TI  - [Leonetti Law, questions and problems].

PMID- 17025006
TI  - [7/10 Cross infections: the particular case of surgical wound infections].

PMID- 17025007
TI  - [4/4 Level II and III analgesics (part 2)].

PMID- 17025008
TI  - [New editorial advice from the Journal of Gerontology and Geriatrics].

PMID- 17025009
TI  - [The nationwide Dementia Program: the LDP cooperates with you].

PMID- 17025010
TI  - [Stability of personality in later life].
AB  - The relation of aging and the stability of personality in late life is evaluated
      by a literature review. The findings of six longitudinal studies reveal that rank
      order consistency continues into old age. The mean-level stability reveals a
      concave curve for 'neuroticism' with an increase after age 80, a decrease for
      'extraversion', and an increase for 'agreeableness'. The methodological and
      conceptual issues of personality assessment with old adults can be resolved by
      using a self report scale which corresponds to the capacities and the lifestyle
      of older adults and by involving age related variables into analyses.

PMID- 17025011
TI  - [Home visits to the elderly in Leiden: an investigation into the effect on
      loneliness].
AB  - In this article the research results are presented of the pilot intervention
      project 'Elderly support home visits'. The aim of this experiment was to reduce
      loneliness among older persons who make use of extramural care. The intervention
      was accompanied by quantitative effect measurements, followed by a qualitative
      study of the process. To determine the effectiveness of the intervention, data on
      loneliness were collected among those persons who have made use of the welfare
      services (the experimental group) and those who were not interested in these
      services (the control group) on three different times: during the first home
      visit and approximately six and twelve months later. The main finding is that the
      intervention did not lead to a substantial reduction in the loneliness score in
      the experimental group. Feelings of loneliness among the participants did reduce,
      but this decline was small and not significant and did not continue in the long
      term. The process evaluation suggests some explanations for this result. This
      article concludes with the limitations of the research design and suggestions for
      improvement of the intervention.

PMID- 17025012
TI  - Looking forward to a general theory on population aging.

PMID- 17025013
TI  - [The handling of acute life-threatening choking in geriatric and nursing home
      patients].
AB  - It is unknown how often choking occurs in geriatric wards and in nursing homes
      and what the treatment and outcomes are in regular practice. A questionnaire was
      sent to Dutch geriatricians (N = 130), nursing home physicians (N = 130), and
      trainees for these disciplines (N = 215), in order to gain information about the
      experience, practice and competence of physicians in choking in geriatric and
      nursing home patients. We also analysed to what extent geriatric and nursing home
      wards were prepared for accurate handling of choking. The response rate was 30%.
      More than half of the responders had experienced an episode of food choking at
      least once in the past five years. The mortality rate in the reported cases was
      high (30%). The majority of the patients who died of choking had not received the
      Heimlich-manoeuvre. Physicians who had attended resuscitation training long ago
      felt as competent to manage a choking episode as physicians that had recently
      attended resuscitation training. Of all geriatric wards and nursing homes, the
      majority lacked a guideline on how to handle in acute food choking. Geriatric
      wards and nursing homes do not seem to be well prepared for acute food choking in
      several aspects. Despite methodological shortcomings of this study, the results
      underline the necessity of clarification of the terms used, and development and
      implementation of guidelines for this important problem.

PMID- 17025014
TI  - Miuraenamides A and B, novel antimicrobial cyclic depsipeptides from a new
      slightly halophilic myxobacterium: taxonomy, production, and biological
      properties.
AB  - A slightly halophilic myxobacterial strain, SMH-27-4, was isolated from nearshore
      soil and shown to belong to a new myxobacterium genus based on phylogenetic
      analysis. This slowly-growing myxobacterium produced the novel antibiotic
      depsipeptides miuraenamides A and B. Their physico-chemical properties and
      molecular formulas, C34H42N3O7Br and C34H42N3O7I, were determined. Miuraenamides
      A exhibited potent and selective inhibition against a phytopathogenic
      microorganism, Phytophthora sp., and moderate inhibition against some fungi and
      yeasts, but was ineffective against bacteria. Both of the metabolites inhibited
      NADH oxidase at IC50 values of 50 microM, suggesting, like beta-methoxyacrylate
      type antibiotics, the electron transfer system of the mitochondrial respiratory
      chain as the cellular target.

PMID- 17025015
TI  - Preparation of erythromycin analogs having functional groups at C-15.
AB  - Chemobiosynthesis has been used to prepare analogs of erythromycins having unique
      functional groups at the 15-position. Using diketide thioester feeding to
      genetically engineered Streptomyces coelicolor, analogs of 6-deoxyerythronolide B
      were prepared having 15-fluoro, 15-chloro, and 15-azido groups. Bioconversion
      using a genetically engineered mutant of Saccharopolyspora erythraea was used to
      produce 15-fluoroerythromycin A and 15-azidoerythromycin A. These new
      erythromycin analogs provide antibacterial macrolides with unique physicochemical
      properties and functional groups that allow for selective derivatization.

PMID- 17025016
TI  - Chitinase inhibitor allosamidin is a signal molecule for chitinase production in
      its producing Streptomyces I. Analysis of the chitinase whose production is
      promoted by allosamidin and growth accelerating activity of allosamidin.
AB  - Allosamidin, a typical secondary metabolite of Streptomyces, has been known as a
      chitinase inhibitor. We found that allosamidin can dramatically promote chitinase
      production and growth of its producer, Streptomyces sp. AJ9463, in a chitin
      medium at a few hundred nM. Allosamidin promoted production of the main chitinase
      detected in the culture filtrate and the chitin-hydrolytic activity of the
      chitinase was not inhibited by allosamidin at the concentration. The gene
      encoding the chitinase showed that it is a family 18 chitinase and it was
      revealed that two genes encoding proteins constructing two-component regulatory
      system were present at 5'-upstream region of the chitinase gene. Allosamidin is
      located in the microbial mycelia cultured in a medium without chitin, but it was
      released from the mycelia by responding to chitin. These results show that
      allosamidin acts as a key signal molecule for chitinase production in its
      producing strain, which may be useful for its growth in chitin-rich environment.

PMID- 17025017
TI  - Chitinase inhibitor allosamidin is a signal molecule for chitinase production in
      its producing Streptomyces II. Mechanism for regulation of chitinase production
      by allosamidin through a two-component regulatory system.
AB  - In Streptomyces sp. AJ9463, a producer of chitinase inhibitor allosamidin,
      allosamidin strongly enhances production of the chitinase mainly secreted to the
      culture broth in a chitin medium. To clarify the mechanism for regulation of the
      chitinase production by allosamidin, a disruption experiment of genes encoding
      proteins constructing a two-component regulatory system present at 5'-upstream
      region of the chitinase gene was performed. In the disruptant obtained,
      allosamidin could not promote the chitinase production, but N, N'
      diacetylchitobiose, which also enhances production of the same chitinase more
      weakly than allosamidin, promoted the chitinase production similarly to the case
      observed in the wild-type strain. Furthermore, by the experiment in an inorganic
      salt solution, it was shown that allosamidin could not induce the chitinase
      production without addition of N, N'-diacetylchitobiose. These results show that
      allosamidin can activate transcription of the chitinase gene through the two
      component regulatory system in the presence of N, N'-diacetylchitobiose.

PMID- 17025018
TI  - Biosynthesis of quinolactacin A, a TNF production inhibitor.
AB  - Quinolactacins, which inhibit tumor necrosis factor production, contain a
      quinolone skeleton conjugated with a y-lactam. The biosynthesis of quinolactacin
      was investigated by feeding experiments using 13C single-labeled precursors
      (sodium [1-13C]acetate, DL-[1-13C]-isoleucine, L-[methyl-13C]methionine, and
      sodium [1-13C]-anthranilate) and D-[U-13C]glucose.

PMID- 17025019
TI  - New dihydrobenzofuran derivative, awajanoran, from marine-derived Acremonium sp.
      AWA16-1.
AB  - Awajanoran (1), a new dihydrobenzofuran derivative, was isolated from an agar
      culture of Acremonium sp. AWA16-1, which had been isolated from sea mud collected
      at Awajishima Island in Japan. The structure of 1 was elucidated on the basis of
      a spectroscopic analysis. This compound inhibited the growth of A549 cells, the
      human lung adenocarcinoma cell line, with an IC50 value of 17 microg/ml, and also
      showed antimicrobial activity.

PMID- 17025020
TI  - Methoxylaricinolic acid, a new sesquiterpene from the fruiting bodies of Stereum
      ostrea.
AB  - Methoxylaricinolic acid (1), a new sesquiterpene with drimane skeleton was
      isolated from the fruiting bodies of Stereum ostrea, together with the known
      compound laricinolic acid (2). The structure of 1 was determined as 12-methoxy-7
      oxo-11-drimanoic acid on the basis of spectroscopic analysis.

PMID- 17025021
TI  - Suppression of multidrug resistance by migrastatin.
AB  - Migrastatin (MGS) is a Streptomyces metabolite that inhibits cancer cell
      migration. In this study, we found that MGS also enhanced the cytotoxicity of
      vinblastine, vincristine, and taxol in P-glycoprotein-overexpressing VJ-300 cells
      and P388/VCR cells. Furthermore, MGS increased the intracellular concentration of
      labeled vinblastine, vincristine, and taxol in both VJ-300 cells and P388/VCR
      cells. P-glycoprotein was photolabeled with [3H]azidopine, but this photolabeling
      was significantly inhibited in the presence of MGS. These results indicated that
      MGS directly interacts with and inhibits P-glycoprotein, thereby sensitizing drug
      resistant cells to anticancer drugs.

PMID- 17025022
TI  - Living donor transplantation--the real gift of life. Procurement and the ethical
      assessment.
AB  - It has been observed during the past 10-15 years a greater disparity between the
      supply of kidneys for transplantation and the demand of patients on waiting
      lists. The number of cadaveric kidneys available for transplantation have not
      increased in many countries. Countries and their societies are faced with a
      choice, let patients with the end- stage renal disease stay on, dialysis giving a
      faster death and a lower quality of life, or decide to introduce the more active
      living donation program. There are countries, historically Scandinavian
      countries, the U.S.A. and U.K., which decided to change medical, social and
      ethical attitudes to help their citizens and patients on dialysis. For many other
      countries approval of the new approach of their donation seems to cause
      difficulties. The main problem for medical staff is the principle Primum non
      nocere (First do no harm), removal of a living kidney conflicts with this
      principle. From the other point of view is the human right of an individual to
      autonomy for donation of a kidney. The donor is completely informed for the risks
      involved in donation of a kidney to an awaiting recipient. The donors reasons for
      donation of the kidney must be understood and family pressure excluded. Where is
      the borderline between the paternalistic approach of the medical personnel
      preventing the altruistic attitude of the donor? How far is the role of the
      medical staff to extend in the assessment of the altruistic nature and goodwill
      of the donors?

PMID- 17025023
TI  - Chronic allograft nephropathy--immunologic and nonimmunologic factors.
AB  - Chronic Allograft Nephropathy (CAN) is one of the most common cause of kidney
      transplant loss. CAN may be caused by immunologic as well as nonimmunologic
      factors which may interfere and increase response. Immunologic factors include
      acute rejection, degree of HLA mismatch, inadequate immunosuppression.
      Nonimmunologic factors contain delayed graft function, ischemia-reperfusion
      injury, nephrotoxicity of calcineurin inhibitors, hyperfiltration, hypertension
      and hyperlipidemia. The histopatological description of CAN may indicate two
      phases of injury. An initial phase by one year include tubulointerstitial
      infiltration in the late phase of CAN arteriolar hyalinosis and
      glomerulosclerosis were revealed. Modification of the immunosuppressive treatment
      with reduction or withdrawal of calcineurin inhibitors may prevent graft loss,
      while addition of nonnephrotoxic agents such as mycophenolate mofetil or
      sirolimus should be considered by the risk of acute rejection. Additionally
      effective management by hypertension and hyperlipidemia is essential.

PMID- 17025024
TI  - Influence of parathyroidectomy on blood pressure and function of the transplanted
      kidney in patients with tertiary hyperparathyroidism.
AB  - BACKGROUND: Tertiary hyperparathyroidism is one of the causes of bone
      demineralisation, nephrolithiasis and a potential risk factor influencing blood
      pressure and excretory graft function in patients after kidney transplantation
      (Tx). The aim of the study is to analyse the influence of parathyroidectomy (PTx)
      on graft function and blood pressure control in these patients. METHODS: 392
      subsequent patients after kidney Tx were included into this analysis. Records of
      84 patients (21.4%) with elevated plasma calcium concentration (> 2.6 mmol/l)
      during observation were reviewed. In 39 patients (9.9%) calcaemia remained
      elevated for over 1 year after kidney Tx. Eleven patients (2.81%) were referred
      for PTx. In 2 cases PTx were performed within the first 6 months, while the 9
      others undergone surgery between 16 and 36 months after Tx. We have evaluated the
      influence of PTx on renal allograft excretory function, blood pressure and the
      number of antihypertensive drugs in kidney transplant patients. RESULTS: In 7 out
      of 11 patients the indication for PTx was renal osteodystrophy, while in other
      cases the indication was the asymptomatic hypercalcaemia. Shortly after surgery
      normalisation of calcaemia was observed in all cases. However the creatinine
      clearance did not changed shortly after PTx (64 +/- 12 vs. 63 +/- 16 ml/min), and
      a slight deterioration of transplanted kidney excretory function was observed in
      2 patients. 12 months after PTx deterioration of GFR (5320 ml/min) of borderline
      significance was found. All patients before PTx suffered from arterial
      hypertension, ten of them were receiving antihypertensive drugs (average 1.6
      medicine per patient). Two weeks after PTx a transient decline of both systolic
      and diastolic blood pressures (-13 +/- 14 mmHg; p = 0.02 and -46 mmHg; p = 0.06,
      respectively) was observed. However there was a negative correlation between
      initial plasma calcium concentration and decline of diastolic blood pressure (R =
      -0.884; p = 0.0003). Six and twelve months after PTx blood pressure values were
      at the same magnitude as before PTx. CONCLUSIONS: (1) Parathyroidectomy and
      normalisation of calcaemia did not influence significantly the excretory
      allograft kidney function. (2) Patients benefit from PTx only with the transient
      improvement of their blood pressure control.

PMID- 17025025
TI  - Acute graft-versus-host disease. The incidence and risk factors.
AB  - OBJECTIVES: Acute graft-versus-host-disease (aGvHD) is a major cause of mortality
      after allogeneic hematopoietic cell transplantation (alloHCT). The goal of this
      study was to evaluate the incidence and risk factors for this complication.
      METHODS: 330 consecutive patients (183 male and 147 female), aged 29 (10-56)
      years, treated with alloHCT in a single center between 1992-2003 were included in
      the analysis. AlloHCT was performed after myeloablative conditioning from either
      related donor (rel-HCT) (n=223) or unrelated voulnteer (URD-HCT) (n=107). GVHD
      prophylaxis consisted of cyclosporin, methotrexate +/- prednisolone. RESULTS:
      Cumulative incidence of grade II-IV and grade III-IV aGvHD equaled 31% and 17%,
      respectively. In multivariate analysis the following factors were associated with
      increased risk of grade II-IV aGvHD: the diagnosis of chronic myeloid leukemia
      (CML) or myelodysplastic syndrome (MDS) (vs. other diagnoses), URD-HCT (vs. Rel
      HCT), years of alloHCT 1992-2001 (vs. 2002-2003), donor age > or =35 years, and
      CD34+ cell dose > or = 4.0 x 10(6)/kg. Increased risk of grade III-IV aGVHD was
      associated with: the use of prednisolone for aGvHD prophylaxis, the diagnosis of
      CML or MDS, and CD3+ cell dose > or =100 x l0(6)/kg. CONCLUSIONS: Incidence of
      aGvHD depends on various recipient-, donor-, and procedure-related factors. This
      should be taken into account when planning treatment for every individual
      patient.

PMID- 17025026
TI  - Conversion from cyclosporine to tacrolimus improves renal function and lipid
      profile after cardiac transplantation.
AB  - BACKGROUND: Calcineurin inhibitors (CNIs) have become the cornerstone of
      immunosuppressive regimens following heart transplantation, but their use is
      associated with nephrotoxicity. The impact on renal function after conversion
      from cyclosporine (CsA) to tacrolimus (TAC) is reported. PATIENTS AND METHODS:
      Fifteen patients (men age 42 +/- 11 years) after cardiac transplantation (HTX)
      were switched from CsA to TAC (mean time after HTX 21 +/- 6 months). There were
      13 male and 2 female patients. Mean cholesterol and LDL level at the time of
      conversion were 217 +/- 65 ml/dl and and 136 +/- 51 mg/100 ml respectively.
      Indication for HTX was ischemic cardiomyopathy (CMP) in 8, congenital in 3 and
      dilatative CMP in the remaining 4 patients. RESULTS: Mean tacrolimus level
      (microg/dl) at 1, 3, 6 and 12 months were 8.6 +/- 3.3, 8.6 +/- 1.4, 9.2 +/- 2.8
      and 9.8 +/- 2.5 respectively. There was a statistically significant improvement
      in creatinine levels at 1, 3, 6 and 12 months after conversion from baseline 1.9
      +/- 0.7 mg/dl to 1.4 +/- 0.5 mg/dl, 1.4 +/- 0.4 mg/dl, 1.3 +/- 0.4 mg/dl and 1.2
      +/- 0.4 mg/dl, respectively (p < 0.05). Furthermore, TAC decreased cholesterol as
      well as LDL-levels during this one-year time frame. CONCLUSION: This study shows
      that conversion from CsA to tacrolimus after orthotopic heart transplantation
      improves renal function.

PMID- 17025027
TI  - L-arginine improves hemodynamic function and coronary flow in an experimental
      model of ischemia-reperfusion injury.
AB  - BACKGROUND: Ischemia and reperfusion injury decrease the release of nitric oxide
      by vessels endothelial cells, which influences postischaemic coronary flow and
      return of left ventricle haemodynamic function. The study was conducted to answer
      the question how addition of L-arginine in cardioplegic and reperfusion fluids
      influences nitric oxide release, inducing the coronary flow and postischaemic
      haemodynamic heart function. MATERIALS AND METHODS: The research was conducted on
      56 rats, divided randomly into seven groups: control (C) and six experimental
      groups (E), where L-arginine was administrated in increasing doses of 0.3, 3.0
      and 30.0 mM/L to cardioplegic (E1, E2 and E3 group) or reperfusion solution (E4,
      E5 and E6 group). To simulate a course of cardiac surgery the following stages of
      experiment were carried out: initial perfusion on the nonworking and working
      heart, cardioplegia, cold cardioplegic arrest and reperfusion of the non-working
      and working heart. RESULTS: Level of nitric oxide during cardioplegic perfusion
      decreased in all groups. During reperfusion on non-working and working heart
      model we noticed the significant increase of nitric oxide for all groups. Along
      with nitric oxide increase, coronary flow increases, whereas with the decrease of
      level of nitric oxide, the coronary flow also diminished. During cardioplegic
      perfusion coronary flow constantly decreased in all groups and during reperfusion
      we observed the new increase of coronary flow. In groups E1, E2 and E3 the
      increase of coronary flow was significant. CONCLUSIONS: Obtained data suggest
      that administration of L-arginine in the preischaemic and in the initial phase of
      reperfusion stimulates increase in nitric oxide release what is positively
      correlated with the increase of coronary flow.

PMID- 17025028
TI  - Electrophysiologic parameters suggesting significant acute cellular rejection of
      the transplanted heart.
AB  - AIM OF THE STUDY: Was to estimate an influence of acute cellular rejection on
      electrophysiologic parameters of allograft and remnants of recipient's heart, in
      patients after orthotopic heart transplantation (OHT). PATIENTS AND METHODS:
      Analysis was performed in 25 OHT recipients (24M/1F, age 48.4 +/- 9 y., ischemic
      time 197 +/- 51 min., donor age 30 +/- 9 y.), who underwent electrophysiological
      study (EPS), along with elective endomyocardial biopsy (EMB), scheduled for the
      1st month after the surgery. Results of EPS were correlated with a degree of
      rejection, assessed with the ISHLT grading system. Grades > or =3A were
      considered a significant cellular rejection. RESULTS: ISHLT grade 0 was observed
      in 8 patients, grade 1A or 1B in 12 patients, and 3A in 5 patients. Frequency of
      transplanted heart rhythm (TH-R) was 691.3+/- 37 ms in patients with ISHLT grade
      0, 690.4 +/- 41 ms in patients with grade 1A or 1B, and 744.4 +/- 668 ms in
      individuals with 3A rejection (p < 0.04, for difference between 0 and 3A groups).
      Intraatrial conduction time (IntrtaCT) was significantly shorter in grade 3A
      group (20.4 +/- 1.6 ms), when compared with patients without rejection (36.2 +/-
      4.9 ms, p < 0.03), or with 1A or 1B rejection (41.5 +/- 13 ms, p < 0.032). Also
      interatrial conduction time (InterCT) was the shortest in patients with 3A
      rejection (53.8 +/- 4.3 ms), when compared with ISHLT grade 0 group (78.5 +/- 7.6
      ms, p < 0.02) and 1A/1B group (74.1 +/- 12 ms, p < 0.023). The other
      characteristics of atria, ventricles and AV-junction performance were comparable
      in all patients. CONCLUSIONS: TH-R, IntraCT and InterCT should be considered as
      the markers of significant cellular rejection in patients after OHT. Further
      analysis involving higher number of patients is warranted.

PMID- 17025029
TI  - Secondary kidney transplantation in a patient 16 years after simultaneous
      pancreas and kidney transplantation--a case report.
AB  - Simultaneous pancreas and kidney transplantation (spktx) is currently the most
      effective method of treatment of type 1 diabetes complicated by renal
      insufficiency. The first successful spktx in Poland was performed in the
      Department of General, Vascular and Transplant Surgery of the Warsaw Medical
      University on the 4th of February 1988. Since then 70 spktx were performed in our
      Department. We present a 44-year-old patient who after 16 years of good function
      of both transplanted organs presented with elevated creatinine levels (>4 mg/dl)
      as a result of chronic rejection of the kidney allograft. On the 22nd of January
      2005 the patient underwent secondary kidney transplantation. The immunosuppresive
      protocol consisted of MMF, CsA and steroids. Humanized anti-lL-2 monoclonal
      antibodies (daclizumab) were used as pre-procedure induction. Using a mid-line
      incision the new kidney graft was anastomosed to the recipient left external
      iliac vessels. The ureter was anastomosed with the bladder without anti reflux
      procedures and the allograft was placed in the retroperitoneum below the
      previously transplanted kidney. Graftectomy of the first kidney allograft was not
      performed. After surgery, normal creatinine parameters were restored to a level
      of 1, 1 mg/dl and an increase in urine output was noted from 1 to 4 liters per
      day. Oral intake of foods was resumed on the 4th postoperative day and no early
      complications were observed. 12 months observation period confirmed stabile
      function of both transplanted organs. Secondary kidney transplantation in
      patients after spktx is technically possible and may be considered an option in
      patients with diminishing function of the first kidney allograft.

PMID- 17025030
TI  - Organ donor with complete situs inversus. Case report and review of the
      literature.
AB  - Complete situs inversus (SI) is a very rare anomaly characterized by the total
      inversion of all abdominal and thoracic organs. SI has been traditionally
      considered an absolute contraindication for liver and heart transplantation. We
      report a case of a donor with complete SI diagnosed at the time of organ recovery
      and we review the literature concerning this anomaly and organ transplantation.

PMID- 17025031
TI  - A case of candida albicans mediastinitis after heart transplantation successfully
      treated with caspofungin.
AB  - Reported here is a case of mediastinitis caused by candida albicans and
      Staphylococcus aureus following a heart transplantation that was successfully
      treated with caspofungin, antibiotics and mediastinal lavage. A review of the
      literature revealed that Candida albicans as a cause of mediastinitis has been
      rarely described. In the few existing reports, evolution was generally fatal,
      especially in immunocompromised patients, despite treatment with antifungal drugs
      and antibiotics.

PMID- 17025032
TI  - [Interfaces between anthropology and the disciplines of the health area: a search
      for new conceptual approaches].
AB  - In studying how societies consider and deal with the human body both as a
      symbolic as well as a biological entity, anthropology situates itself at the
      nexus of two axes. These occupy a central epistemological space in the discipline
      and consist of: the analysis of social facts, ranging from their manifestations
      in the lives of individuals, to those manifested in the collective life of
      groups; and the observation of reality, ranging from its material to its
      immaterial or ideal aspects. This singular position enriches the anthropology of
      health and opens up theoretical and methodological perspectives that go beyond
      those of medical anthropology and the anthropology of illness in their restricted
      focus upon the social parameters of biological disorders, the causes of
      suffering, and misfortune. This paper attempts to reflect upon examples which
      encompass the above two axes showing how the anthropology of health can improve
      our understanding.

PMID- 17025033
TI  - [Contributions for the knowledge on nursing as per the perception phenomenology
      of Merleau-Ponty].
AB  - This text approaches some contributions of Maurice Merleau-Ponty for the
      knowledge in Nursing starting from the reflection on his work Phenomenology of
      Perception. Furthermore, it discusses the challenges of the construction of
      knowledge and on how the philosophical knowledge of a certain thinker can
      contribute for the search of taking care-care actions in Nursing that allow
      recognizing the expressive capacity of the human beings. It retakes the
      expressive phenomenon in the approaching and distancing relations present in the
      interactive process of taking care. The text intends understanding some of the
      several dimensions comprised by Nursing and how they go together along the
      universe of taking care.

PMID- 17025034
TI  - [Teaching apprenticeship in psychiatric nursing: an experience during the
      postgraduate period].
AB  - I present my experience related to an internship on teaching upon developing
      activities in the discipline of Psychiatric Nursing II, during the Nursing
      graduation at Universidade Federal de Santa Catarina in the first semester of
      2004. It is a theoretical-practical subject, divided into two blocks. The
      internships take place in a psychiatric hospital and in the community through
      domicile visits. I have found out that the psychiatric hospital was the scenario
      of several significances. The students appreciated the domicile visits, even
      under a few difficulties. After a discussion based on the relevant literature, I
      came to the conclusion that this experience was beneficial to me for allowing the
      integration between graduation and postgraduation.

PMID- 17025035
TI  - [Education in health in the curriculum of a nursing course: learning for
      teaching].
AB  - The education in health constitutes the role of the nurse in the different
      contexts of the work but in practice it has been observed that these actions not
      always are adequate. It is assumed that one of the causes is the scarce
      theoretical contribution of the teachers. The objective of this article is
      reflecting on how a graduation course of nursing has been approaching the health
      education with its pupils. It is a documental research being the data collected
      in the teaching plans of the nursing graduatin course. The analysis evidenced
      that the subject is not approached adequately in all of the disciplines, as it
      should be. The drawn conclusion is that the education of the nurse must broaden
      the theoretical information on the practices in health education.

PMID- 17025036
TI  - [Maternal breast-feeding: changes occurred in the father's conjugal life].
AB  - It is a qualitative study with the objective of identifying the man's perception
      regarding the changes that took place in his marital relationship during the
      child's breast-feeding. The data were collected through interview with 13
      fathers. The results indicate that men develop attitudes and feelings relative to
      the son and the wife; they recognize that the alterations in their marital
      relationship are more evident during the first three months of the child's life
      and they try to understand or to demonstrate indifference towards the changes.
      Although breastfeeding results in modifications in the spouses' relationship, the
      fathers do not consider them as something negative in their lives.

PMID- 17025037
TI  - [Bathing and the colonization of the preterm newborn skin].
AB  - This article aims at determining the bathing role in skin colonization of preterm
      newborn by reviewing the literature from MEDLINE database. Clinical researches
      have demonstrated that bathing with soap triggers pH increase interfering with
      the skin physiological protection and provoking changes in the cutaneous
      microflora composition. Preterm neonates in NICU tend to acquire nosocomial skin
      flora from the action of bathing with cleansing products on the epidermal barrier
      function with direct consequences on the skin colonization.

PMID- 17025038
TI  - [Conflicts and dilemmas of nurses who work in surgical centers of macro-regional
      hospitals].
AB  - This research aimed at describing the conflicts and ethical dilemmas experienced
      by twelve nurses working in Surgical Centers of macro-regional hospitals in Rio
      Grande do Sul, Brazil. The analysis of the interview data was carried out through
      the Content Analysis technique. The data were discussed through technical
      deontologica base and communicative action theory. It has been found out that the
      nurses working at Surgical Centers face conflicts and dilemmas daily. They are
      related to the lack of infrastructure to meet the deman resulting in disrespect
      and violation of some principles of the deontology code.

PMID- 17025039
TI  - [Knowing the history and the life conditions of subjects with spinal cord
      lesions].
AB  - This study aimed at characterizing the victims of medullar lesion (LM) and their
      daily needs. The data were collected in Maringi, Parani, Brasil, from 32 subjects
      by using semi-structured interview. The results revealed that most of them (84%)
      were males, had low education level (71,9%) and, at the time of the accident,
      they found themselves within the economically active age group (19 to 38 years
      old). Concerning their daily needs, we have identified among them a higher
      independence for feeding, excreting and buccal and body hygiene, and a higher
      dependence upon moving. Taking care to meet the specific necessities of the
      subject with LM is a challenge for the health professionals.

PMID- 17025040
TI  - [Integrated curriculum: analyzing the performance of the participative planning].
AB  - This study approaches an exploratory investigation that intended analyzing the
      application of theoretical bases that sustain the Situation Strategic Planning
      (SSP), for the development of the performance of the participative planning in
      the integrated curriculum of Nursing Course. The data were collected through
      semistructured interview with the students and professionals involved in the
      construction of a project that used the SSP referential in the hospital unit. The
      analysis of the interviews data was done by utilizing the technique of content
      analysis in the thematic mode. The findings indicated the limitations and
      breakthroughs in the performance development of the participative planning in an
      integrated curriculum.

PMID- 17025041
TI  - [Health education for varicose ulcer patients through group activities].
AB  - It is a report on the group activities carried out with carriers of varicose
      ulcer in a health unit in Porto Alegre, Rio Grande do Sul, Brazil. The varicose
      ulcer presents factors, besides the biological ones, which interfere in the
      cicatrization, in the relapse cases and in its effective resolution. The proposed
      activities aimed at producing behavior changes with the intention of achieving
      self-care, providing information, socializing the participants, and stimulating
      cooperation, searching for joint solutions, aggregating interdisciplinary spirit
      and improving the care. Two groups have been formed and a thematic schedule
      established. The results have showed higher adhesion to the treatment, behavioral
      changes, and adapted and more effective attitudes of the health team.

PMID- 17025042
TI  - [Alcoholism families: the search for nexus of maintenance, accommodation and re
      standardization of alcoholism behaviors].
AB  - An investigation carried out with alcoholist families aimed at identifying
      behaviors of maintenance, accommodation and re-standardization of the familiar
      functioning vis-a-vis the use of alcohol and proposing alternatives for re
      standardization of the alcoholist behavior. We have worked with three families
      selected according to some preestablished criteria. It is an exploratory and
      qualitative study. The data have been collected during the domicile therapeutic
      care to the family group. The identification of nexus of maintenance,
      accommodation and re-standardization of alcoholist behaviors in the families have
      made possible the construction of proposals of re-standardization of the
      alcoholist family functioning, in the perspective of alcohol not being the
      catalyst of the family relations anymore.

PMID- 17025043
TI  - [The nurse in charge of the materials and sterilization center and the perception
      of his or her social role].
AB  - This study has used the speech analysis in order to understand how the nurses of
      the Material and Sterilization Center (MSC) perceive their social roles and
      relate them with the structure of health care and with the process of the nursing
      care. The interviewed nurses appreciate their work and identify themselves with
      an already given social role. This valuation derives much more from the
      administrative role than from the one that is specific to the CMS. Within this
      context, there is no tension between their work and the relation, or none, with
      the care by the nurse. They express a perception of negative external value
      regarding their work, which is sufficient enough to generate tension and
      discomfort.

PMID- 17025044
TI  - [Human papillomavirus: repercussion on the woman's health in the family context].
AB  - This study aimed at analyzing the problems related to the Human Papillomavirus
      (HPV) and its relation with the women's health in the family context. It is a
      study of reflexive analysis related to the theme, starting from a literature
      review and searching for an association with the reality studied. The educative
      approach is indispensable in the context of the woman's health, taking into
      account that when the HPV affects the woman, it causes emotional instability,
      feelings of guilt and, many times, conjugal disharmony. The nurse plays an
      essential role in the control of the HPV and must develop actions of promotion
      and prevention, taking care individually of the family and the community.

PMID- 17025045
TI  - [Friendship relationship in the geriatric institution].
AB  - This article aims at understanding what the friend and friendship represent for
      the elderly in the context of the geriatric home. One utilized the qualitative
      approach while the techniques for data collection were: thematic interview and
      indirect participant observation. The collection period was from April to June
      2003, in a geriatric home located in the city of Salvador, Bahia. 15 elderly
      subjects were interviewed. The used analysis was of thematic contents. We
      understood that the definition of friend and friendship for the institutionalized
      elderly is associated with his shortages in the life of the geriatric home. One
      comes to the conclusion that the friendship relations established transcend ages,
      cultures and physical conditions.

PMID- 17025046
TI  - [Feelings of pleasure and suffering of teachers in the implementation of a
      curriculum].
AB  - The research identified feelings of pleasure and suffering experienced by 30
      nurse professors in their job by verifying the dimensions of the valuation, of
      the exhaustion and of the recognition before the change of the labor process in
      view of the implementation of an innovating curriculum change. It is a
      quantitative study based on Dejours' theoretical referential by utilizing
      Likert's scale. The drawn conclusion is that the professors have more pleasure
      than suffering in their job because they feel valued, recognized and do not feel
      exhausted by their activities. These data highlight the importance of the
      relationship among the professors and their chores, peers and institution,
      considering that here is the place where the factors that contribute to feelings
      of pleasure and suffering are established.

PMID- 17025047
TI  - [Utilization of the problematizing pedagogy in the nursing graduation for the
      care of the aggressive patient].
AB  - This investigation aims at identifying, along with the graduation students, the
      prevailing difficulties in attending the aggressive patient. In this study, an
      instrument has been applied on the first and on the last day of apprenticeship to
      third-year students. The analysis occurred in a qualitative way by making use of
      Paulo Freire's thematic analysis. It has been observed that most of the students
      have no experience on attending an aggressive patient and they do not feel in
      conditions to assist in this situation. The drawn conclusion is therefore that
      the student realizes his difficulties and an effective change must be made in the
      way and in the time of teaching this content.

PMID- 17025049
TI  - Molecular manipulation based on allosteric crown-appended units and related
      systems.
AB  - Synthesis of many potentially useful molecular units by chemists promotes the
      development of methods for constructing supramolecular architectures. Indeed,
      programmed supramolecular interactions play crucial roles in the preparation of
      well-defined nanoscale assemblies. This review highlights successful approaches
      in designing for specific functions systematically. The incorporation and
      synergistic communication of conformation-switchable segments into molecules
      bears great promise. Allostery, which is often observed in naturally occurring
      proteins, provides a hint for molecular manipulation. In supramolecular chemistry
      crown ethers can serve not only as substrate-binding sites but also as function
      tuning sites. With the combination of synthetic versatility and well-tailored
      design, diverse capabilities (molecular recognition, catalytic properties,
      chirality, actuation, and so on) become possible at the molecular or mesoscopic
      level. The synthetic preparation of advanced molecular units allows the systems
      to become smarter, and promise nanosystems with programmable functions. This
      review considers mainly the use of crown ethers which act as anchoring as well as
      allosteric sites, from the standpoint of design for molecular manipulation. It
      also gives a brief discussion of recent progress in molecular manipulation, based
      on related systems. The "synthetic systems" described in the present review
      should contribute to not only to more elaborate "chemical systems", but also to
      the evolving field of "molecular machinery", that can utilize these systems.

PMID- 17025048
TI  - [The role of the health professionals in cases of domestic violence: the report
      of an experience].
AB  - It is a report on an experience - a volunteer apprenticeship carried out at Viva
      Maria Passage Home located in Porto Alegre, Rio Grande do Sul, Brazil. This study
      aimed at learning about the domestic violence issue, identifying the role of the
      health professionals in the care to women who are victims of violence and
      performing activities with the dwellers and their children. Such activities
      comprised workshops on health education. The clientele involved women and their
      children who lived in the passage home between August and December 2001. The
      mentioned experience evidences the possibility of breaking up the violence chain
      that links people who is submitted to it.

PMID- 17025050
TI  - Assemblies of biomaterials in mesoporous media.
AB  - Assemblies of biomaterials onto mechanically stable inorganic structure are
      advantageous for the practical applications because of the potential to improve
      the stability and performance of biomaterials in the biocatalytic processes.
      Among many kinds of inorganic materials, mesoporous materials such as mesoporous
      silica and mesoporous carbon have attracted special attention owing to their well
      defined structures and perfectly controlled pore geometries, which would lead to
      unique functions such as size selective adsorption of biomaterials. In the first
      part of this review, adsorption behaviors of proteins, enzymes, vitamins, and
      amino acids in aqueous solutions onto mesoporous media are systematically
      explained. Pore geometries (pore diameter and volume) of mesoporous materials are
      the crucial factors for the size selective adsorption of biomaterials, especially
      proteins, which often have a size comparable to pore dimension. The studies on
      the adsorption of biomaterials on the mesoporous carbon reveal that hydrophobic
      interaction between guest molecules and surface of the mesoporous materials is an
      important parameter which controls the amount of biomaterials adsorption.
      Enhanced adsorption of biomaterials was commonly observed at their isoelectric
      point, where electrostatic repulsion is minimized between the biomaterials. In
      addition, several functions such as biomolecular separation, reactor function,
      controlled drug release, and photochemical properties are discussed in the latter
      sections. Studies on assemblies of biomaterials in mesoporous media are still in
      initial stage, but the development of appropriately designed mesoporous materials
      would powerfully promote researches in these fascinating unexplored fields.

PMID- 17025051
TI  - Metal ion assembly in macromolecules.
AB  - Self-assembled organic-inorganic hybrid nano-materials have recently received
      much attention due to their novel and original functions, including new
      electronic, optical, magnetic, and catalytic properties. Especially, reactions in
      organic-metallic hybrid materials are closely related to biological reactions,
      such as the reactions in metal-containing protein, and the controlled metal ions
      assembly into organic polymers becomes very important. In the first part of this
      review, recent progresses in two types of organic-inorganic hybrid nano-materials
      (Organic compounds [character: see text] inorganic mesoporous materials and Metal
      ions [character: see text] organic polymer) are summarized. In the latter parts,
      dendrimer-metal complexes, examples of nature-mimetic materials, are introduced,
      and their controlled metal assembly in dendrimer and their application are
      reviewed.

PMID- 17025052
TI  - Template-synthesized nanotubes through layer-by-layer assembly under charge
      interaction.
AB  - Aqueous polymer nanotubes can be assembled by combining the layer-by-layer (LbL)
      assembly and template technique under charge interaction. This method allows lots
      of species, especially in an aqueous system to form a tubular structure in the
      pores of the template. The tubes functions can be readily modified by introducing
      various functional components. Such assembled nanotubes are often mechanically
      stable and highly flexible. They have also numerous potential applications in
      delivering materials.

PMID- 17025053
TI  - Chiral mesoporous materials based on the self-assembly.
AB  - Ordered mesoporous materials with various structures are synthesized based on the
      self-assembly of surfactant and inorganic precursors and covered by several
      excellent reviews. However, less work has been directed to chiral structured
      mesoporous materials, although these could have wide-ranging applications on the
      manufacturing of enantio-pure chemicals and pharmaceuticals as catalysts and
      separation media with both shape selectivity and enantioselectivity. This short
      review will address the synthesis of chiral mesoporous materials by chiral
      organic compounds templating route, covering single and 2-dimensional ordered
      chiral channel mesoporous materials. Non-porous helical fiber, atomic-scale
      enantio-morphism and zeolite-like materials with three-dimensional helical pores
      are beyond the scope of this paper.

PMID- 17025054
TI  - Probing the stability of biocompatible sodium hyaluronate/chitosan nanocoatings
      against changes in salinity and pH.
AB  - The stability of polyelectrolyte multilayer assemblies was investigated with
      emphasis on the effects of solution ionic strength, pH, and polymer molecular
      weight on the film thickness and surface topography. The multilayers consisting
      of two polysaccharides, the polyanion sodium hyaluronate (HA) and the polycation
      chitosan (CH) were studied using surface plasmon resonance (SPR) spectroscopy,
      impedance quartz crystal microbalance (QCM), and atomic force microscopy (AFM).
      SPR/QCM experiments show that coatings consisting of four HA/CH bilayers
      assembled at pH 4.5 in the presence of 0.15 M NaCl are stable in NaCl solutions
      of concentration less than 0.8 M. These multilayers are stable when placed in
      contact with aqueous solutions ranging in pH from 3.5 to 9. The molecular weight
      of the polysaccharides has only a marginal effect on the stability of the films
      in the range explored here (HA: Mn = 360,000 or 31,000 g/mol; CH: Mn = 160,000 or
      30,000 g/mol). AFM imaging reveals that different mechanisms may account for the
      multilayers stability versus salt and pH treatments. While increasing the ionic
      strength induces reorganization of the surface topography from isolated spherical
      islets to elongated worm-like features, changes in pH have no appreciable effects
      on the coating topography prior to complete disintegration.

PMID- 17025055
TI  - Fabrication and electrocatalysis of self-assembly directed gold nanoparticles
      anchored carbon nanotubes modified electrode.
AB  - A self-assembly directed approach was adopted to modify glassy carbon electrode
      (GC) with gold nanoparticles incorporation and the electrocatalytic performance
      of self-assembly modified electrode, GC/SA-Au-ME was critically evaluated for the
      oxidation of ascorbic acid (AA). The modification involves the dispersion of
      multi-wall carbon nanotube (MWNT) and an inclusion complex, beta-cyclodextrin-4
      aminothiophenol on the surface of GC electrode in the presence of
      cetyltrimethylammonium bromide (CTAB). Gold nanoparticles were deposited into the
      self-assembled sites to fabricate the modified electrode, GC/SA-Au-ME. Another
      electrode (GC-Au-ME) was fabricated under similar conditions in the absence of
      CTAB. The electrocatalytic activity of the modified electrodes (GC/SA-Au-ME and
      GC-Au-ME) towards the oxidation of AA was critically compared. Cyclic
      voltammetry, chronoamperometry, and double potential chronoamperometry were used
      to evaluate the characteristics of the modified electrodes. The self-assembled
      electrode (GC/SA-Au-ME) shows excellent electrocatalytic activity over the other
      electrode, GC-Au-ME. Augmented current response, faster electron transfer
      kinetics (with a rate constant for electron transfer process as 3.25 x 10(4) cm3
      mol(-1) s(-1)), linear range of response for the analyte (1-50 mM with an
      extended detection limit to 1 microM), better sensitivity, and selectivity were
      witnessed for the self-assembly directed modified electrode.

PMID- 17025056
TI  - Synthesis and characterization of nanocrystalline mesoporous zirconia using
      supercritical drying.
AB  - Synthesis of nano-crystalline zirconia aerogel was done by sol-gel technique and
      supercritical drying using n-propanol solvent at and above supercritical
      temperature (235-280 degrees C) and pressure (48-52 bar) of n-propanol. Zirconia
      xerogel samples have also been prepared by conventional thermal drying method to
      compare with the super critically dried samples. Crystalline phase, crystallite
      size, surface area, pore volume, and pore size distribution were determined for
      all the samples in detail to understand the effect of gel drying methods on these
      properties. Supercritical drying of zirconia gel was observed to give thermally
      stable, nano-crystalline, tetragonal zirconia aerogels having high specific
      surface area and porosity with narrow and uniform pore size distribution as
      compared to thermally dried zirconia. With supercritical drying, zirconia samples
      show the formation of only mesopores whereas in thermally dried samples,
      substantial amount of micropores are observed along with mesopores. The samples
      prepared using supercritical drying yield nano-crystalline zirconia with smaller
      crystallite size (4-6 nm) as compared to higher crystallite size (13-20 nm)
      observed with thermally dried zirconia.

PMID- 17025057
TI  - Nanostructuring of poly(diphenylamine) inside the galleries of montmorillonite
      organo clay through self-assembly approach.
AB  - Hollow spheres of poly(diphenylamine) (PDPA) was prepared by confining PDPA in
      the galleries of montmorillonite organo clay modified with organoammonium cations
      (MMT). At first instant, diphenylamine (DPA) was loaded into the galleries of MMT
      and subjected to subsequent oxidative polymerization to form PDPA. beta
      naphthalene sulfonic acid (NSA) was used as medium to influence self-assembly of
      DPA inside the galleries of MMT. Polymerization of self assembled structure
      resulted hollow spheres of PDPA inside galleries of MMT. X-ray diffraction
      analysis (XRD), field emission transmission electron microscopy (FETEM), Fourier
      transform infra-red spectroscopy (FT-IR) and thermogravimetric analysis (TGA)
      were used to characterize the composites. Transmission emission microscopy of the
      composite shows the hollow spherical morphology of PDPA. FT-IR, UV-Visible
      spectroscopy, conductivity measurement and X-ray photoelectron spectroscopy were
      used to characterize the PDPA extracted from MMT galleries. PDPA extracted from
      MMT galleries was found to have difference in electronic property than PDPA
      formed by the conventional method, due to the confinement effect.

PMID- 17025058
TI  - Bio-nanocomposites by assembling of gelatin and layered perovskite mixed oxides.
AB  - A new class of bio-nanocomposites based on hybrid gelatin-perovskite hydrogels
      was prepared by mixing exfoliated perovskite-tetraalkylammonium species in
      aqueous suspensions with gelatin solutions. Colloidal nanosheets derived from the
      CsCa2Nb3O10 layered perovskite re-stacked in the gelatin solutions give bio
      nanocomposite materials with different content in the inorganic moiety. These
      films can be easily processed as homogeneous self-supported films. The partial
      exfoliation of the pristine mixed oxide is produced from alkylammonium exchanged
      phases, being the tetraalkylammonium ions (tetraethylammonium, TEA+) an efficient
      intermediate to give the colloid phase constituted by well exfoliated materials
      useful to generate homogeneous films. The nanosheets are highly oriented in the
      bio-nanocomposite films in agreement with the XRD patterns and the FTIR
      dichroism. This orientation could be considered as a characteristic of this type
      of hybrid materials leading to new potential applications. In this way, we have
      observed that the assembling of perovskite to gelatin produces a greater increase
      of the dielectric permittivity than the dielectric loss in the studied samples.

PMID- 17025059
TI  - Organization of nanoparticles on hard substrates using block copolymer films as
      templates.
AB  - We present a technique for the organization of pre-synthesized nanoparticles on
      hard substrates, using block copolymer films as sacrificial templates. A thin
      block copolymer film is dip-coated on the substrate of interest and the sample is
      exposed to a solution containing nanoparticles. Spontaneous preferential
      adsorption of the nanoparticles on one phase of the block copolymer film results
      in their lateral organization. An oxygen plasma etch is used to remove the
      polymer film; the nanoparticles end up organized on the substrate. We demonstrate
      that this is a general approach for the patterning of inorganic nanoparticles on
      hard substrates, showing the organization of metal and semiconductor
      nanoparticles having different chemistries at the particle/solvent and
      solvent/polymer interfaces. The nanoparticle patterns that we present have
      typical periodicities in the nanometer scale. In some cases, microcontact
      printing is used to create a double length scale of organization, on the
      micrometer and on the nanometer level. The characteristic periodicity of the
      template is studied with respect to the nanoparticle size in order to optimize
      the organization. Finally, we describe how to extend this technique for the
      production of continuous gold nanowires on hard substrates. We expect that the
      flexibility of this approach and the degree of control that can be obtained over
      nanoparticle organization should make it a powerful tool for nanoscale
      fabrication.

PMID- 17025060
TI  - Clay-assisted disaggregation and stabilization in hemicyanine Langmuir-Blodgett
      films.
AB  - Hybrid Langmuir-Blodgett films consisting of an amphiphilic hemicyanine
      derivative and a smectite clay have been fabricated employing a clay suspension
      as the subphase. This hybridization was demonstrated to be a convenient and
      effective means of achieving complete disaggregation of dye chromophores in a
      Langmuir-Blodgett film without reducing chromophore density in the two
      dimensional lattice. UV-visible electronic absorption and optical second-harmonic
      generation measurements indicated that the molecular alignment in the films was
      stabilized by the hybridization.

PMID- 17025061
TI  - Multiple nano-blast synthesis of PT/8Y-ZP composite nanopowders.
AB  - We demonstrate a processing technique based on the synthesis of ceramic
      nanopowders and simultaneous impregnation with metallic nanoparticles by multiple
      'nano-blasts' of embeded cyclotrimethylene trinitramine in preliminary engineered
      multi-component nano-reactors. 'Nano-blasts' of impregnated cyclotrimethylene
      trinitramine deagglomerate the nanopowder due to the high energetic impacts of
      the blast waves, while the decomposition of compounds and their solid-solubility
      is enhanced by the extremely high local temperature generated during the nano
      explosions. We applied this technique to produce nanosized agglomerate-free 8
      mol% yttria-doped cubic zirconia aggregates with an average size of 53 nm
      impregnated with 10 mass% of platinum particles of 2-14 nm.

PMID- 17025062
TI  - Exfoliation of layers in NaxCoO2.
AB  - We proposed and developed an exfoliation process for layer-structured NaxCoO2 to
      prepare CoO nanosheets. Na+ ion exchange by acid treatment was utilized to expand
      the spacing between the two CoO2 layers in NaxCoO2. Ethylamine was then
      effectively utilized for the exfoliation of cobalt oxide sheets having nanometer
      order thickness and high aspect ratio. CoO nanosheets were observed by TEM
      micrographs and electron diffraction patterns after drying. Further efforts are
      needed for the application of exfoliated sheets to an integration process to
      fabricate self-assembled nanomaterials such as desired layer structures composed
      of two (or more) kinds of nanosheets.

PMID- 17025063
TI  - Chemomechanical nanolithography: nanografting on silicon and factors impacting
      linewidth.
AB  - We present a two-fold extension of previous work on Atomic Force Microscope-based
      chemomechanical functionalization: (1) chemomechanical nanografting, which
      extends chemomechanical functionalization to a more stable initial surface, and
      (2) linewidth studies that show the impact of force and Atomic Force Microscope
      probe tip wear on patterning resolution. Alkene, alcohol, and alkyl halide
      molecules were nanografted to silicon and imaged with in situ atomic force
      microscopy, time-of-flight secondary ion mass spectrometry with Automated eXpert
      Spectrum Image Analysis, and scanning electron microscopy. Chemomechanical
      nanografting demonstrated linewidths down to 50 nm. Lines written on hydrogen
      terminated silicon were used to explore the impact of tip radius and tip wear on
      linewidth when using Si3N4 coated tips.

PMID- 17025064
TI  - Electronic properties of a single-walled carbon nanotube/150mer-porphyrin system
      measured by point-contact current imaging atomic force microscopy.
AB  - The electronic properties of a single-walled carbon nanotube/150mer of porphyrin
      polymer wire system were investigated. Current-voltage (I-V) curves were measured
      simultaneously along with topographic observations using point-contact current
      imaging atomic force microscopy. Symmetric I-V curves were obtained at bare
      single-walled carbon nanotubes but characteristic asymmetrical rectifying
      behavior was found at the single-walled carbon nanotube/150mer-porphyrin
      junctions. This finding is of key importance for the development of new nanoscale
      molecular electronic devices.

PMID- 17025065
TI  - Preparation and characterization of polypeptide-stabilized gold nanoparticles.
AB  - Helical polypeptides have a highly rigid conformation. In order to control self
      assembling structure in nanoscale, the rigidity of the stabilizing molecules,
      which is working as scaffolds, is highly important. Furthermore, the molecular
      lengths of polypeptides can be readily controlled by using their unique
      polymerization methods. In this study, we have used helical polypeptides as the
      stabilizing reagent of metal nanoparticles. As for rigid helical polypeptides,
      poly(gamma-benzyl-L-glutamate) (PBLG) was selected, and was synthesized by N
      carboxylic acid anhydride (NCA) polymerization. Preparation of helical
      polypeptide-stabilized gold nanoparticles using a two-phase reduction process
      from the corresponding metal salts with NaBH4 is therefore introduced. PBLG
      itself did not have good stabilizing ability for metal nanoparticles and a
      terminal attaching ligand was indispensable for nanoparticle stabilization and,
      for this purpose, lipoic acid was selected. It is estimated that lipoic acid
      functionalized polypeptide molecules were attached perpendicularly to the
      particle surface by lipoic acid group. The size and structure, as well as
      assembling will be discussed in this manuscript.

PMID- 17025066
TI  - Nano-engineered microcapsules of tannic acid and chitosan for protein
      encapsulation.
AB  - Tannic acid (TA), a high molecular weight polyphenol of natural origin, was
      assembled in alternation with chitosan (CH) using a layer-by-layer technique. The
      deposition of tannic acid and chitosan layers on flat supports was monitored by
      quartz crystal microbalance, UV-vis spectroscopy, and electrophoretic mobility
      measurements on microparticles. Hollow (TA/CH)4 capsules were built and their
      permeability as a function of pH and molecular weight of a penetrating compound
      was investigated. The pH-permeability threshold for TA/CH capsules is shifted to
      lower pH for 2 pH units, as compared with commonly used
      polyallylamine/polystyrene sulfonate capsules. A more pronounced dependence of
      the TA/CH capsules' permeability on molecular weight of encapsulated substances
      allows better control over their release properties. Bovine serum albumin was
      loaded into (TA/CH)4 capsules using a pH-driven method and released by decreasing
      pH. Biocompatible tannic acid/chitosan films and capsules have advantages toward
      capsules made of synthetic polyelectrolytes for drug encapsulation and as
      delivery and depot systems. Incorporating a layer of tannic acid with proved
      antioxidant and antimicrobial properties into capsule walls, provides defense for
      encapsulated materials.

PMID- 17025067
TI  - Syntheses of Ag, PbSe, and PbTe nanocrystals and their binary self-assembly
      exploration at low size-ratio.
AB  - Nanocrystals of Ag, PbSe, and PbTe were prepared via a high-temperature organic
      solution approach, respectively. Using a size-selection technique, the size
      distribution of each set of nanocrystals could be fine-tuned and finally
      monodisperse products were achieved. Superlattice structure of binary self
      assemblies in low size-ratio were also explored and characterized by transmission
      electron microscopy. It is realized that a success of achieving binary self
      assembly pattern is greatly dependent on several key factors including particle
      size-distributions, relative concentrations of both components, as well as the
      size-ratios between Ag and PbSe (or PbTe) nanocrystals.

PMID- 17025068
TI  - Self-assembled monolayer of carboxyl-terminated poly(amido amine) dendrimer.
AB  - Adlayer formation and adsorption structure of 2.5th-generation poly(amido amine)
      dendrimer with carboxyl-terminated groups on solid substrates were investigated
      by atomic force microscopy, surface plasmon resonance spectroscopy, and surface
      enhanced infrared absorption spectroscopy. Dendrimer molecules are not uniformly
      adsorbed on solid surface but form aggregates with a width of approximately 100
      nm and a height less than 1 nm. Adsorption reaches in equilibrium at 100-1000
      sec, depending on the dendrimer concentration. The adsorption-desorption process
      is considerably reproducible and repeatable. Although the adsorption at
      equilibrium increases with dendrimer concentration and reaches maximum at neutral
      pH, monolayer is always maintained after the desorption with solvent. This
      indicates the formation of self-assembled monolayer. Such monolayer is preserved
      even at the variation of pH. Although most carboxylates are protonated at acidic
      pH, small amount of carboxylate remains even at acidic pH. The adsorption
      structure of dendrimer was illustrated.

PMID- 17025069
TI  - Influence of the side functionalization of quinquethiophene-S,S-dioxides on the
      morphology of blends with poly(3-hexylthiophene): scanning force microscopy
      reveals.
AB  - Blends of an electron donor, i.e. a regioregular poly(3-hexylthiophene) (P3HT),
      with electron acceptors, a series of soluble quinquethiophene-S,S-dioxides (T5Os)
      bearing different alkyl side groups were self-assembled at surfaces. Scanning
      Force Microscopy (SFM) studies revealed that while the T5O symmetrically
      functionalized with two hexyl groups in the central thiophene (1) self-organizes
      into micrometer sized crystals embedded in a grainy matrix of P3HT, by
      substituting the central thiophene of 1 with one hexyl and one methyl unit (2)
      smaller and less anisotropic crystals of the acceptor having a sub-micrometer
      scale size were formed. The generation of these crystals is due to the joint
      effect of different non-covalent intermolecular interactions between the T5Os
      that self-segregate from the P3HT. By derivatizing the compound 1 with cyclo
      hexyl moieties in the four external thiophenes molecule 3 was obtained. Such
      system was found to assemble into grainy disordered structures when co-deposited
      with P3HT, providing evidence for the absence of a phase segregation between the
      two components. Generally, the self-assembly at surfaces is governed by the
      interplay of intramolecular as well as intermolecular and interfacial
      interactions. In the present case, the cyclo-hexyl side groups in 3 both induce
      an intramolecular loss of planarity of the thiophene rings and hinders
      intermolecular interactions, reducing the tendency of the molecules to self
      associate forming large crystals, whereas the symmetrical functionalization of
      the two central thiophenes with hexyl chains favours the crystallization of the
      T5O. The reported results demonstrate that subtle differences in the chemical
      functionalization can lead to different types of molecular architectures at
      surfaces. This is of importance since controlling the self-organization of pi
      conjugated molecules at surfaces towards pre-programmed assemblies is a viable
      approach to enhance their electronic and luminescent properties, which should
      help to improve the performance of organic devices.

PMID- 17025070
TI  - Nuclear magnetic resonance study of fullerene-like WS2.
AB  - Inorganic fullerene-like nanoparticles of WS2 (IF-WS2), are synthesized by a
      reaction of tungsten oxide with molecular hydrogen and hydrogen sulfide. The
      synthesized nanoparticles appear as large agglomerates (>40 microns), each one
      counting thousands of IF nanoparticles. 1H nuclear magnetic resonance study of
      these nanoparticles is reported. The measurements show that the prepared product
      contains water (and possibly some hydrogen) molecules that occupy the voids in
      the central part of the fullerene-like nanoparticles and the nanopores between
      the adhering IF-WS2 particles. Defects in the IF-WS2 structure, arising due to
      the strain release during the folding of the layers, may result in additional
      sites for the absorbed water. Vacuum annealing of the powder leads to substantial
      reduction in the amount of absorbed water molecules.

PMID- 17025071
TI  - Self-assembly of well-defined polyacrylamide-polystyrene copolymer on fibrillar
      clays via ultrasonic-assisted surface-initiated atom transfer radical
      polymerization.
AB  - Well-defined polyacrylamide-polystyrene copolymers were grafted from the
      fibrillar clay, attapulgite, by a four-step self-assembly process: (i) the gamma
      aminopropyltriethoxyl silane was self-assembled onto the surfaces of the
      attapulgite; (ii) the surface amino groups were amidated with bromoacetylbromide;
      (iii) the bromo-acetamide modified attapulgite was used as macro-initiator for
      the surface-initiated atom transfer radical polymerization of styrene with the
      catalyst of the complex of 1,10-phenanthroline and Cu(I)Br; (iv) the polystyrene
      grafted attapulgite was then used as macroinitiator for the polymerization of
      acrylamide. The two steps of the surface-initiated atom transfer radical
      polymerizations were all conducted under ultrasonic irradiation at room
      temperature. The product, polyacrylamide-polystyrene copolymers grafted
      attapulgite, had been characterized with elemental analysis, Fourier transform
      infrared spectroscopy, Thermogravimetric analysis (TGA), X-ray photoelectron
      spectroscopy, X-ray diffractometry, and transmission electron microscopy.

PMID- 17025072
TI  - Surface-modified mesoporous silicas as recyclable adsorbents of an endocrine
      disrupter, bisphenol A.
AB  - Surface-modified mesoporous silicas (MSs) were investigated for recyclable
      adsorption of an endocrine disrupter, bisphenol A (BPA). Surface-modified MSs
      were prepared by (i) post-synthesis surface modification of MSs using surface
      hydroxyl groups and organosilanes (m-MS) and by (ii) co-condensation of
      tetraethoxysilane and the corresponding organosilanes (d-MS). Infrared
      measurements indicated that organic groups mainly existed on the surface of m-MS,
      which resulted in a surface characterized by high hydrophobicity. Both organic
      groups and isolated hydroxyl groups existed on the surface of d-MS, resulting in
      both hydrophobicity and hydrophilicity on the surface. The amount of BPA adsorbed
      on surface-modified MSs per organic group was similar for m-MS and d-MS, however,
      the d-MS established equilibrium for BPA adsorption faster than m-MS, as measured
      by UV-vis spectra. A larger amount of BPA per surface area could be adsorbed on
      carbon materials than on the surface-modified MSs, however, the regeneration of
      carbon materials by washing could not be done easily. The surface-modified MSs
      retain adsorption capacity for BPA after several regeneration cycles,
      demonstrating that the surface-modified MSs are effective recyclable adsorbents
      of the endocrine disrupter, bisphenol A.

PMID- 17025073
TI  - Ultrathin poly(ethylene glycol) monolayers formed by chemical vapor deposition on
      silicon substrates.
AB  - Poly(ethylene glycol) (PEG) monolayer was formed through the chemisorption of a
      vapor phase organosilane. Photochemically cleaned silicon substrate covered with
      native oxide (SiO2/Si) was exposed to a vapor of an organosilane, that is, 2
      (methoxy[polyethyleneoxy]propyl) trimethoxysilane (MPEOPS) for 1-7 h at 150
      degrees C. The resulting sample surfaces became relatively hydrophobic showing a
      static water-contact angle of ca. 67 +/- 2 degrees and their thickness was
      ellipsometrically measured to be ca. 0.8 +/- 0.1 nm. Atomic force microscopy
      confirmed that the sample surface was extremely smooth and homogeneous.
      Isoelectric point of the MPEOPS-monolayer-covered SiO2/Si substrate was measured
      to be at around pH 4.9, which was close to that of the methoxytri(ethylene
      glycol)-terminated alkanethiol SAM on gold (pH 4.3). Furthermore, we demonstrated
      micropatterning of the MPEOPS monolayer based on a direct photolithography using
      172 nm VUV light through a photomask. A well-defined microstructure composed of 5
      microm x 25 microm rectangular features was successfully fabricated on a MPEOPS
      monolayer surface. Subsequently treated it by spatially defined CVD treatment
      using aminosilane molecule, binary microstructures composed of PEG and amino
      terminated surfaces were successfully fabricated.

PMID- 17025074
TI  - Polymetallated porphyrin ultrathin films as transducing elements for molecular
      devices and logic gates.
AB  - Meso-tetrapyridylporphyrins peripherally coordinated to four ruthenium complexes,
      such as [Ru(bpy)2Cl] and [Ru(5-ClPhen)2Cl] (bpy = 2,2'-bipyridine; Phen = 1,10
      phenanthroline), provide a versatile class of molecular materials in which the
      complexes act as co-factors, inducing electronic effects and acting as electron
      transfer relays and electron pools or sinks, depending upon their oxidation
      state. These cationic porphyrins can be assembled into thin films by conventional
      methods, or into organized layer-by-layer structures by combining with negatively
      charged tetrasulfonated porphyrins or phthalocyanines. Their electrocatalytic and
      photoelectrochemical properties have been successfully exploited in chemical
      sensors. Their usefulness in molecular logic gates are being demonstrated by
      using modified transparent conducting electrodes in miniaturized flow injection
      cells. In such designs, the chemical, electrochemical, and light inputs can be
      readily combined to perform the basic logic functions, such as AND, OR, and NOT,
      for molecular computing.

PMID- 17025075
TI  - Electrostatic layer-by-layer assembly of ultrathin films containing hexacyclen
      and p-sulfonatocalix[n]arene macrocycles.
AB  - Formation and characteristic properties of new layer-by-layer (LbL) assembled
      ultrathin films based on 1,4,7,10,13,16-hexaazacyclooctadecane (aza6) and p
      sulfonatocalix[n]arenes with n=6 (calix6) and n=8 (calix8) are described. In
      particular, multilayered films of aza6 and polystyrenesulfonate (PSS), aza6 and
      calix8 or calix6, aza6 and hexacyanoferrate(II) (HCFII), calix8 and
      lanthanum(III), and calix8, 18-crown-6 and lanthanum(III) were investigated. The
      films were prepared upon alternating electrostatic adsorption of the cationic and
      anionic compounds from aqueous solution at charged substrates. Since the
      protonation of aza6 proceeds over a wide pH range, the film formation is strongly
      pH dependent. Linear growth of aza6/PSS films is found at pH 1.7 and 6.0, and
      superlinear growth at pH 0.9, 2.7, 3.7, and 5.0. The high affinity of aza6
      towards inorganic ions favours the formation of LbL-assemblies of aza6 and HCFII
      counterions. Exposure of these films to Fe(III) leads to formation of Prussian
      Blue at the surface. The high affinity of p-sulfonato-calix[n]arenes towards
      La(III) favours the formation of LbL-assemblies of calix6 or calix8 and
      lanthanum. If additional 18-crown-6 is present in the La(III)-containing dipping
      solution, multilayered films of calix8, 18-crown-6 and La(III) are obtained.

PMID- 17025076
TI  - Remarkable difference of phase transition behaviors between Langmuir monolayers
      and aqueous bilayer vesicles of oligopeptide-carrying lipids.
AB  - In this research, we synthesized six kinds of oligopeptide-carrying lipids which
      possessing glycine, diglycine, triglycine, alanine, dialanine, and trialanine
      residues (see Figure 1 for their formulae), and systematically investigated their
      phase transition behaviors both at the air-water interface and in aqueous bilayer
      vesicles. pi-A Isotherms of Langmuir monolayers of these lipids were measured at
      the air-water interfaces under varied temperature conditions and were analyzed
      based on compressibility of the monolayers. Above the specific temperature, the
      transition pressure from its expanded phase to condensed phase is not
      distinguishable with the collapse pressure of the monolayer, i.e., the monolayer
      collapses directly from the expanded phase without forming the condensed phase.
      This temperature was defined as the phase transition temperature of the
      monolayer, which was compared with the phase transition temperature of the
      corresponding bilayer vesicle in water. The phase transition temperatures of the
      oligoglycine-carrying lipids and oligoalanine-carrying lipids are significantly
      different at the air-water interface, while the corresponding difference is not
      obvious in their aqueous bilayer vesicles. Consideration based on molecular
      structures suggests necessity of the water mediation for effective formation of
      hydrogen bonding between the oligopeptide residues directly connected to dialkyl
      chains. Therefore, the differences in water accessibility to the films may cause
      the difference of the phase transition behaviors of the oligopeptide-carrying
      lipids between the Langmuir monolayers and the aqueous bilayer vesicles. Although
      the proposed mechanism is not fully supported by experimental evidences, the data
      presented here clearly demonstrated the presence of significant difference of the
      phase transition properties between the Langmuir monolayers at the air-water
      interface and aqueous bilayer vesicles of the oligopeptide-carrying lipids.

PMID- 17025077
TI  - Oxidation-reduction dynamics in layer-by-layer self-assembled redox
      polyelectrolyte multilayer modified electrodes.
AB  - The oxidation-reduction dynamics of layer-by-layer (LbL) self-assembled redox
      polyelectrolyte multilayer films on electrodes has been studied by cyclic
      voltammetry, chrono-amperometry, electrochemical quartz crystal microbalance
      (EQCM), ellipsometry, and Fourier transform reflection-absorption infrared
      spectroscopy (FT-IRRAS). Thin layer electrochemistry with fast electron transfer
      at the underlying metal-film interface and charge propagation by electron hopping
      between adjacent redox sites in the finite thin film has been observed. An almost
      ideal cyclic voltammetry for a fixed number of redox sites in the thin surface
      film suggests that the multilayer can be fully oxidized and reduced in the time
      scale of the experiment (RT/vF > or = 0.05 sec). The electron hopping diffusion
      coefficient 3 x 10(-10) cm2 s(-1) was obtained from the chronoamperometric
      current transient and the ellipsometric thickness. Both cyclic voltammetry and
      potential step yield a surface osmium bipyridyl redox concentration of gamma Os =
      4 x 10(-10) mol x cm(-2) for (PAH-Os)5(PVS)4 film. Exchange of ions and solvent
      occur simultaneously to the charge injection as revealed by the EQCM mass change
      and the ellipsometric thickness change. From the end-to-end mass-to-charge linear
      relationship, the molar mass of the ionic and neutral species exchanged largely
      exceeds the molar mass of any ions or solvent which suggests an important flux of
      solvent during redox switching. An initial "break in" effect is observed for the
      first oxidation-reduction cycles when a newly self-assembled film equilibrates
      with the electrolyte as charge is injected during the electrochemical
      perturbation.

PMID- 17025078
TI  - Application of photoresponsive polymers carrying crown ether and spirobenzopyran
      side chains to photochemical valve.
AB  - A vinyl copolymer carrying crown ether and spirobenzopyran side chains, which
      undergoes significant photoinduced rheology changes, i.e., contraction and
      extension of its polymer chain, was applied to a material for photocontrol system
      of solvent permeation rate, so-called, photochemical valve. Macroporous
      polyethylene membranes coated by the crown ether-spirobenzopyran copolymer can
      work as a functional membrane controlling solvent permeation rate
      photochemically. UV-light irradiation on the photoresponsive membrane decreased
      the permeation rate of hexane, due to the increased polarity of the membrane
      pore, which was in turn derived from the photoisomerization of its
      spirobenzopyran moiety to the corresponding ionic merocyanine form. The following
      visible-light irradiation on the membrane restored the permeation rate by
      isomerization back to the electrically neutral spiropyran form. To the contrary,
      the permeation of ethanol through the membrane was enhanced by UV-light
      irradiation due to the increase in the apparent membrane pore size induced by the
      polymer chain contraction and vice versa by visible light. Similar photoresponses
      in the permeation rate of nonpolar and polar solvents were also observed with a
      sintered glass filter modified chemically by both silane-coupling reagents
      containing crown ether and spirobenzopyran moieties.

PMID- 17025079
TI  - Single supramolecule spectroscopy of natural and alkaline-treated chlorosomes
      from green sulfur photosynthetic bacteria.
AB  - Fluorescence emission properties of intact and alkaline-treated chlorosomes
      containing bacteriochlorophyll(BChl)-c, d, and e, which were isolated from four
      species of green sulfur photosynthetic bacteria, were successfully studied at the
      single-unit level using a total internal reflection fluorescence microscope.
      Single intact chlorosomes containing BChl-c from Chlorobium (Chl.) tepidum
      exhibited heterogeneous emission bands of BChl-c self-aggregates. In contrast,
      fluorescence spectra of chlorosomal BChl self-aggregates in single intact
      chlorosomes from the other three Chlorobium species were less heterogeneous than
      those from Chi. tepidum. Removal of energy-accepting BChl-a/protein complexes
      called baseplates from the intact chlorosomes by treatments with alkaline media
      hardly changed spectral shapes of BChl aggregates and their peak distributions at
      the single-chlorosome level. The similarity of spectral properties at the single
      unit level between intact and alkaline-treated chlorosomes of four Chlorobium
      species clearly indicated that the removal of base-plates from intact chlorosomes
      by the alkaline-treatment did not affect BChl self-aggregates inside single
      chlorosomes.

PMID- 17025080
TI  - Transition-metal (Ti,V,Cr,Mn,Fe,Co,Cu) containing ordered nanoporous materials:
      novel heterogeneous catalysts for selective oxidation reactions.
AB  - Transition-metal (Ti,V,Cr,Mn,Fe,Co,Cu) containing periodic nanoporous catalysts,
      were synthesized hydrothermally and characterized using various analytical and
      spectroscopic techniques. The catalytic performance of the different catalysts
      was systematically evaluated with a detailed study on TiMCM-41. All the catalysts
      showed promise for the selective oxidation of cycloalkanes, viz., cyclohexane,
      cyclooctane, and cyclododecane, under mild reaction conditions. Furthermore,
      these mesoporous molecular sieves were also active for all the chosen reactions
      even after several recycling and/or washing treatments. Among the various
      materials under investigation, the catalysts TiMCM-41 and VMCM-41 showed much
      higher substrate conversion and excellent product selectivity in conjunction with
      a minimal leaching of the active species. More importantly, the influence of pore
      size on the catalytic activity of the bulkier substrates such as cyclooctane and
      cyclododecane is demonstrated.

PMID- 17025081
TI  - Immobilization of lysozyme onto pore-engineered mesoporous AISBA-15.
AB  - In this research, hydrothermally stable mesoporous AISBA-15 materials have been
      used as adsorbents for systematic research on the lysozyme adsorption. Stability
      of the AISBA-15 adsorbents and the lysozyme molecules after the adsorption
      experiments for several days in aqueous solutions were confirmed by X-ray
      diffraction (XRD) measurement and FT-IR spectroscopy, respectively. The amount of
      the lysozyme adsorption can easily be controlled by the pore diameter and pore
      volume the mesoporous adsorbent, but an unreasonable effect of the surface area
      on the protein adsorption capacity was observed. The results of the effect of the
      pore diameter on the lysozyme adsorption suggest that the adsorption might
      partially be influenced by kinetically favorable edge-on type orientation on the
      confined mesopore. However, the final adsorption amount of the lysozyme can be
      well regenerated by models based on the side-on adsorption in dense packing. The
      present research also confirms the importance of appropriate "pore-engineering"
      for immobilization of bio-function on mesoporous materials.

PMID- 17025082
TI  - Formation of chiral surface with enantiomeric tartaric acid on gemini-structured
      self-assembled monolayers.
AB  - Chiral surfaces were prepared by L, D, and Meso-tartaric acids (TAs) adsorbed on
      gemini-structured self-assembled monolayers (SAMs) composed of ethylenebis [(12
      mercaptododecyl) dimethyl ammonium bromide] (HS-gQA-SH). The formation and
      structure of the chiral surfaces were characterized by surface plasmon resonance
      spectroscopy (SPR) and Fourier transform infrared-reflection adsorption
      spectroscopy (FTIR-RAS). The thickness of enantiomeric TA layers on the HS-gQA-SH
      SAM was estimated to be c.a. 5-6 angstroms regardless of their chirality, in good
      agreement with the height of TA molecules anchoring on the surface with two COOH
      groups. All the TAs on the HS-gQA-SH SAM exhibit the same ionization state
      independent of their chirality in their vibration bands of carboxylic groups. We
      attempted a second-layer adsorption of the enantiomeric TAs on L-TA monomolecular
      layer (L-TA SAM) precomposed on the HS-gQA-SH. A strong affinity between first
      and second TA layers resulted in the film growth when their chirality is
      identical (i.e., L-TA on L-TA SAM). We found the structure of second L-TA layer
      was completely different from that of the first layer, where a crystalline-like L
      TA phase was found as a predominant component. Our results imply a preferential
      crystalline growth of chiral molecules on the same chiral surface, which may lead
      to a work for optical resolution into two enantiomers at a solid-liquid
      interface.

PMID- 17025083
TI  - Construction and electrochemistry of Langmuir-Blodgett films of fullerene lipid
      composite/hybrid materials.
AB  - Studies of the electrochemistry of Langmuir-Blodgett (LB) films of C70/artificial
      lipids including tridodecylmethylammonium bromide (3C12N+Br-, 1),
      didodecylphosphate (2C12PO4H, 2), and dioleoylphosphatidylcholine (DOPC, 3) and
      of LB films of a fullerene lipid (4) bearing triple alkyl chains on a C60 moiety
      on electrodes were carried out in aqueous media. Stable Langmuir monolayers of
      fullerene C70/artificial lipid composites and the fullerene lipid (4) were formed
      at the air-water interface and these monolayers were transferred onto electrodes
      as LB films. Here, we focus on the importance of cationic matrix lipid films to
      the facile electrochemistry of C70 embedded in a LB film of cationic lipids on an
      electrode in aqueous media. On the basis of the electrolyte dependence and the
      charge dependence of the matrix lipids, a possible electron-transfer mechanism of
      the C70/artificial lipid LB film-modified electrodes is presented.
      Electrochemistry of a LB film of 4 was also obtained in an aqueous medium. We
      demonstrate that the introduction of the chemistry of lipid bilayer membranes to
      the LB films of fullerenes guides us toward the construction of fullerene/lipid
      bilayer devices.

PMID- 17025084
TI  - Microwave synthesis of metallosilicate zeolites with fibrous morphology.
AB  - In this paper, we report syntheses of silicalite (Si-MFI) zeolite crystals with
      tetravalent metal ions incorporated to synthesize metallosilicalite (M-MFI; M =
      Sn, Zr, Sn/Zr, Ti/Zr) zeolite crystals by using microwave irradiation reactions.
      Beta-Diketonate (acetylacetone) was used as a chelating ligand of the metal
      precursors, in order to reduce their hydrolysis rates and, therefore, to enhance
      framework incorporation of each metal in the syntheses of M-MFI zeolites. The
      zeolite crystals formed show puck-like morphology, and these crystals are stacked
      to form fibers with the degree of self-assembly varied depending on the nature of
      the tetravalent metal ion used. Importantly, the self-assembly of the zeolite
      crystals and the resultant fibrous morphology are observed only when the
      substituting metal ions are present. Powder X-ray diffraction, infrared and
      ultraviolet diffuse reflectance spectroscopic data all indicate that Sn and Ti
      atoms are well substituted for Si, but Zr is not well incorporated in the
      resulting MFI crystals. These results are discussed in terms of the ionic sizes
      and bulk dielectric constants of the corresponding metal oxides of the
      substituting metal ions.

PMID- 17025085
TI  - Synthesis of polypyridine-graft-PEG copolymer for protein repellent and stable
      interface.
AB  - Polypyridine grafted with poly(ethylene glycol) (Py-g-PEG) have been synthesized.
      Radical copolymerization of methyl-terminated PEG macromonomer with 4
      pyridylmethyl methacrylate homogeneously proceeded and the obtained copolymer
      spontaneously adsorbs from aqueous solution onto gold surfaces, where the
      pyridine parts act as the multipoint anchor to the surface and the PEG parts
      provide the strong steric repulsion between the chains. As a result, the highly
      protein repellent and stable surface was constructed through multipoint pyridine
      attachment as compared with singlepoint pyridine attachment. Py-g-PEGs thus
      synthesized are promising material to functionalize metal and semiconductor
      material and to self-assemble into micelle in biotechnological and biomedical
      field.

PMID- 17025086
TI  - Flexible solar-cell from zinc oxide nanocrystalline sheets self-assembled by an
      in-situ electrodeposition process.
AB  - Zinc oxide nanocrystalline sheets were self-assembled on a flexible polymer
      substrate to act as the electrode of dye-sensitized solar cells by an in situ
      construction electrodeposition process. It was discovered that the nanosheet
      based solar cell exhibited better performance than a nanoparticle-based solar
      cell or a well-oriented nanowire-based solar cell. The nanosheet microstructure
      has advantages which include the depression of loss during photoelectron
      transport, the increase of dye compound adsorption, and the enhance of incident
      light capture. As a result, the performance of dye-sensitized solar cells can be
      obviously improved. This success provides a feasible bottom-up approach for
      integrating a solar cell together with nanodevices and microcircuits on a
      flexible substrate which can work with self-supplied solar energy.

PMID- 17025087
TI  - Effects of addition of supramolecular assembly on the anatase nanocrystalline
      precipitation of sol-gel derived SiO2-TiO2 coating films by hot-water treatment.
AB  - Effects of the addition of a supramolecular assembly of cetyltrimethylammonium
      bromide in SiO2-TiO2 gel films on the formation of anatase type TiO2 nanocrystals
      with hot-water treatment were investigated. Anatase nanocrystals were formed in
      the whole SiO2-TiO2 gel films with the addition of cetyltrimethylammonium bromide
      by the treatment, whereas the nanocrystals were formed only on the film surface
      in the case of gel films without cetyltrimethylammonium bromide.
      Cetyltrimethylammonium bromide molecules in the SiO2-TiO2 gel films were
      completely removed by the hot-water treatment and the following UV irradiation.
      In the usual procedure for preparation of porous materials, the removal of
      template molecular assemblies required high temperature treatment over 400
      degrees C. In this system, all the processes were performed at temperatures less
      than 100 degrees C. Additionally, the porous structure produced by the removal of
      micellar assembly allowed anatase nanocrystals to be formed inside the films.
      Therefore, the method presented in this work provides us with the novel
      photocatalyst coatings of porous membrane with highly-dispersed TiO2 nanocrystals
      via low temperature process.

PMID- 17025088
TI  - Ordered, self-organized cobalt nanodots in Co-diamond-like carbon thin films.
AB  - A formation process for ordered, self-organized cobalt (Co) nanodots in diamond
      like carbon (DLC) thin films deposited by magnetron sputtering in a plasma
      assisted Ar/CH4 discharge is presented. episilon-Co dots -5 nm in diameter,
      separated by 1-2 nm DLC boundaries and arranged in hexagonal arrays were produced
      on Si substrates. The formation mechanism relies on a self-organization process
      which is based on surface energy minimization and local magnetic field
      interaction. The proposed plasma-assisted process presents a controlled and cost
      effective bottom-up nanofabrication approach for the production of well-ordered
      magnetic nanodots based on self-organization.

PMID- 17025089
TI  - Heterogeneous photocatalytic degradation of methanol over uranyl-anchored
      nanoporous MCM-41 and MCM-48.
AB  - The vapor-phase photodegradation of methanol to carbon dioxide was carried out
      over uranyl-anchored nanoporous MCM-41 and MCM-48 hosts (designated as
      UO2(2+)/MCM-41 and UO2(2+)/MCM-48, respectively) under simulated light and
      ambient conditions. Preliminary results indicate that the photoactivity of the
      latter is considerably decreased as compared to the former due to the presence of
      a smaller fraction of photoactive uranyl (UO2(2+)) ions in UO2(2+)/MCM-48.

PMID- 17025090
TI  - Nanosphere lithography from template-directed colloidal sphere assemblies.
AB  - Conventional nanosphere lithography holds the drawbacks of lacking precise
      control over the shape and architecture of the resultant nanostructures. In this
      work, nanoimprinting lithography was used to construct various desired patterns
      on a polymer film coated on a silicon substrate. The patterns were then used as
      templates to direct the self-assembly of silica colloidal spheres, forming
      colloidal assemblies with well-controlled sizes, shapes, and structures.
      Subsequent nanosphere lithography using template-directed colloidal sphere
      assemblies resulted in complex nanostructures that can not be obtained using the
      conventional nanosphere lithography method.

PMID- 17025091
TI  - Circularly polarized laser emission induced by supramolecular chirality in
      cholesteric liquid crystals.
AB  - This paper describes the circularly polarized spectroscopic studies on absorption
      and emission of an achiral fluorescent dye embedded in cholesteric liquid
      crystals (CLCs). Optical excitation of the dye-doped CLC cell with a linearly
      polarized laser brought about the two laser emission peaks at longer and shorter
      reflection band edges of the CLC host through the internal laser feedback effect
      of the one-dimensional CLC photonic band-gap. At this stage, the optically
      excited laser emissions showed circularly polarized characteristic, even though
      the excitation beam was linearly polarized. The circularly polarized direction of
      the laser emission was determined by molecular chirality of only few mol% of the
      enantiomeric chiral dopant in this molecular system.

PMID- 17025092
TI  - One-dimensional self-assembly of alkoxy-capped silicon nanoparticles.
AB  - We demonstrate here a novel method for self-assembling in dimensional alignment
      the alkoxy-capped silicon nanoparticles synthesized through a room-temperature
      chemical route. The alkoxy-capped silicon nanoparticles were prepared via a
      reduction of silicon tetrachloride with sodium-naphthalide and subsequent surface
      capsulation with 1-octanol monolayers. In the present method, a sublimation
      process, which was employed as a final purification process for removing the
      residual naphthalene, influenced significantly on the final morphology of the
      resultant nanoparticles. Scanning transmission electron microscope (STEM)
      confirmed the spherical nanoparticles on a holey carbon grid after sublimation
      process, while only the fibril-like morphology just before sublimation process.
      In the former sample, the resultant particle size was measured by STEM to be
      about 9.5 nm +/- 3.4 nm. On the other hand, in the latter sample, the fibril-like
      structures were shaped by self-assembled silicon nanoparticles in dimensional
      alignment. The diameters and lengths of the fibril-like assemblies were
      approximately measured to be 10 to 20 nm and over 5 microm, respectively.

PMID- 17025093
TI  - pH sensitive organic-inorganic layered nanomaterials by self-assembly of
      indigocarmine between the inorganic layers.
AB  - New pH sensitive organic-inorganic intercalation compounds having different
      interlayer spacing were prepared. Zn-Al layered double hydroxide (LDH) is an
      anion exchangeable inorganic layered compound whose interlayer spacing is 0.76
      nm. In the reactions of indigocarmine (IDC) with the calcined Zn-Al LDH at pH = 7
      (LDH-IDC7), interlayer spacing increased to 2.25 nm. The interlayer spacing of
      LDH-IDC7 decreased to 1.89 nm by the treatment in basic solution. In the reaction
      of IDC with the calcined Zn-Al LDH at pH = 10 (LDH-IDC10), interlayer spacing of
      the intercalation compounds was 1.89 nm. The interlayer spacing of these
      intercalation compounds was changed reversibly by the treatments in acidic or
      basic solution.

PMID- 17025094
TI  - High-yield self-assembly of flower-like ZnO nanostructures.
AB  - High-yield three-dimensional (3D) flower-like nanostructures self-assembled from
      1 D ZnO nanorods and nanotubes are experimentally demonstrated. The Zn and O
      terminated crystal planes of ZnO nanorods results in positively and negatively
      charged top (001) and bottom (00-1) surfaces, respectively. The nanorods self
      assembled into 3D nanostructures via the electrostatic interaction between the
      crystal planes with opposite charges. Moreover, on the basis of the different
      stability of polar and nonpolar planes in wurtzite-type ZnO, the nanorods based
      3D nanostructures transformed into nanotubes based ones spontaneously. This
      provides a new approach to prepare multi-dimensional materials without the
      necessity to employ any external intervention.

PMID- 17025095
TI  - Surface pressure induced charge transfer between fullerene and tetrathiafulvalene
      derivative in Langmuir-Blodgett films.
AB  - Structures and electronic states of a 1:1 mixture of bis-tetrathiafulvalene
      annulated macrocycle (1) and C60 in Langmuir films at the air-water interface and
      Langmuir-Blodgett (LB) films on solid substrates were examined. Compression of
      the Langmuir films induced for the first time a phase transition from a weakly
      interacting state without charge transfer (CT) to a neutral CT state. The
      scanning force microscope images of LB films transferred onto mica by a single
      withdrawal showed quite different spatial patterns depending on the CT states.
      When deposited at around 1 mNm(-1), a domain structure with 3 nm height was
      obtained, which corresponded to the state without CT interaction. Contrastingly,
      once the CT interaction was induced by applying surface pressure, a network
      structure was observed with a height of 6 nm. The CT band, whose transition
      moment was almost parallel to the substrate surface, was observed at 11.5 x 10(3)
      cm(-1) in the polarized UV-VIS-NIR spectra of the films deposited at 9 mNm(-1).
      The phase transition was irreversible, although the surface pressure-area
      isotherm showed a reversible behavior below 9 mNm(-1). The morphology and
      electronic state of the film was controllable merely by changing the surface
      pressure at the air-water interface.

PMID- 17025096
TI  - Self-assembled molecular pattern by chemical lithography and interfacial chemical
      reactions.
AB  - The fabrication of lipid-modified molecular patterns by Chemical Lithography
      combined with interfacial chemical reactions is reported. In this method, self
      assembled monolayers (SAMs) of 4'-nitro-1,1'-biphenyl-4-thiol (NBT) were
      structured by Chemical Lithography which produced cross-linked 4'-amino-1,1'
      biphenyl-4-thiol (cABT) monolayers within a nitro-terminated (NBT) matrix. The
      terminal amino groups in the cABT monolayer were diazotized to create diazo
      cations, and the lipid monolayer with negative charge was assembled on the diazo
      regions by electrostatic attraction. Under the exposure of UV light, the
      photoreaction occurs. The diazonium groups interacting with the lipid headgroups
      via electrostatic attraction decompose and release N2 which leads to the lipid
      monolayer covalently attaching to the cABT region. The presence of phosphorus in
      X-ray photoelectron spectra (XPS) reveals the binding of the phospholipid layer
      to the cABT surface. Atomic force microscopy (AFM) images display that lipid
      modified molecular patterns with different sizes and shapes and with a thickness
      of ca. 2.5 nm have been formed. The resulting lipid-modified molecular patterns
      are considered to be a first step towards obtaining stable biointerfacing
      patterns and studying biomolecular recognition.

PMID- 17025097
TI  - Patterning of ZrO2 precursor through a gas-generated self-assembly route.
AB  - We designed a gas-generated self-assembly route for patterning of ZrO2 precursor
      films from an aqueous peroxozirconium solution. Molecular oxygen generated during
      the decomposition of zirconium complex selectively aggregated on the hydrophobic
      surface of self-assembled monolayers, which was photo-modified to be a template.
      This gas layer prevented the solution from attaching to the substrate, so as the
      deposition of zirconia precursor occurred almost entirely on the hydrophilic
      sites. In comparison, only isolated islands of deposits were observed on
      hydrophobic sites, which may be attributed to contamination or adsorption of
      colloids during the preparation of samples. The resolution of pattern was well
      improved by using such a gas-generated process. In addition, this approach can be
      also extended to prepare other micropatterns.

PMID- 17025098
TI  - Two-dimensional self-organization of gold nanoparticles on supramolecular
      aggregates.
AB  - Alkanethiol-capped gold (Au) nanoparticles, dispersed in toluene and spin-coated
      on atactic polystyrene films that are themselves spin-coated on fused quartz
      plates, self-assemble into a characteristic two-dimensional pattern-a network of
      the Au-thiol nano-composite separating polystyrene 'islands' of dimensions around
      200 nm. This pattern changes on varying the concentration of the nanoparticles in
      the coating solution, evolving into the network from isolated nanoparticle
      clusters, and then going over to a distribution of 'pinholes' on a surface
      covered by the nano-composite, resembling a partially wetted surface with near
      full coverage. Study of the pristine polystyrene surface reveals a pattern of low
      cohesion regions separating 'islands' of polystyrene, where the latter are known
      to be supramolecular aggregates. It is suggested that these regions play the role
      of low-resistance channels to the flow of the nano-composite during spin coating.

PMID- 17025099
TI  - Palladium and gold nanoparticle array films formed by using self-assembly of
      block copolymer.
AB  - The well-arrayed Pd and Au nanoparticle thin films were successfully prepared by
      making use of self-assembled PS-b-P4VP block copolymer (BCP) as a mask for the
      reduction of PdCl2 deposited on glass substrate. The films consisted of
      spherialcal nanoparticles with an average diameter of about 45 nm. For monitoring
      the size, shape and array formation of Pd nanopaticle films, this procedure was
      proved better to the conventional process in which PdCl2 impregnated in the
      channels of self assembled BCP film is reduced to form nanoparticle array. This
      observations of Pd nanoparticle array film formation is supported by the AFM and
      UV-VIS studies of Au nanoparticle array films formed by conventional method.

PMID- 17025100
TI  - Nontrivial quantum effect of defect-induced magnetic moments in spin chains.
AB  - Low dimensional strongly correlated systems have great potential for new quantum
      devices. Among them, quantum wires are actively investigated with development of
      new methods based on self-organized formation. For magnetic wires (chains),
      impurity doping, which causes inhomogeneity of magnetic interaction, can bring
      new magnetic properties to the systems. In the present study, the effect of
      inhomogeneity (defect) on magnetic chains with bond alternation is focused on.
      Defects induce local moments in the magnetic chains at low temperatures. However,
      depending on the relation of the distance between the defects, the magnetic
      profile is found to be drastically changed.

PMID- 17025101
TI  - Progress on mechanics of carbon nanotubes and derived materials.
AB  - This review focuses on the most recent progress in understanding mechanical
      properties of individual carbon nanotubes (CNT), carbon nanotube arrays, random
      networks, and polymer matrix composites. The key factors that influence the
      mechanical properties of these new (nano)materials are identified and discussed.
      The critical issue appears to be the load transfer efficiency; between nanotubes
      when organized in bundles, ropes, and networks; between matrix and nanotubes in
      composites. Among the different paths used to increase load transfer, cross
      linking by irradiation is emphasized. A particular attention is paid on the role
      of nanotubes as nucleating agents in polymer composites, initiating the formation
      of a crystalline polymer sheath that has important consequence on the mechanical
      properties. The reinforcing element to be considered in that case is not CNT
      alone but CNT covered with a cylinder of crystalline polymer. Whereas a lot of
      effort has been focused on the problem of dispersion, it appears that the problem
      of nanotube-matrix interphase is almost as important. Recent works show that
      appropriate surface functionalization can be used both to improve dispersion and
      tailor the interphase. Nanotube surface engineering combined with methods
      producing oriented nanocomposites should bring exceptional materials in the near
      future.

PMID- 17025102
TI  - Applications of carbon nanotubes-based biomaterials in biomedical nanotechnology.
AB  - One of the facets of nanotechnology applications is the immense opportunities
      they offer for new developments in medicine and health sciences. Carbon nanotubes
      (CNTs) have particularly attracted attention for designing new monitoring systems
      for environment and living cells as well as nanosensors. Carbon nanotubes-based
      biomaterials are also employed as support for active prosthesis or functional
      matrices in reparation of parts of the human body. These nanostructures are
      studied as molecular-level building blocks for the complex and miniaturized
      medical device, and substrate for stimulation of cellular growth. The CNTs are
      cylindrical shaped with caged molecules which can act as nanoscale containers for
      molecular species, well required for biomolecular recognition and drug delivery
      systems. Endowed with very large aspect ratios, an excellent electrical
      conductivity and inertness along with mechanical robustness, nanotubes found
      enormous applications in molecular electronics and bioelectronics. The ballistic
      electrical behaviour of SWNTs conjugated with functionalization promotes a large
      variety of biosensors for individual molecules. Actuative response of CNTs is
      considered very promising feature for nanodevices, micro-robots and artificial
      muscles. An description of CNTs based biomaterials is attempted in this review,
      in order to point out their enormous potential for biomedical nanotechnology and
      nanobiotechnology.

PMID- 17025103
TI  - Nanotopography: cellular responses to nanostructured materials.
AB  - Several in vitro and in vivo experiments have shown that nanostructured
      materials, which mimic the nanometer topography of the native tissues, improve
      biocompatible responses, and result in better tissue integration in medical
      implants. Understanding various aspects of nanotopography is extremely important
      for better designs of these devices. In this review paper, recent progress in the
      fabrication, characterization, biological responses, and application of
      nanostructured materials are discussed. Specifically, materials such as ceramics
      and polymers used to manufacture nanostructured surfaces are briefly introduced.
      Techniques for fabrication and characterization of nanostructured materials are
      also explored. Cellular responses such as morphology, alignment, adhesion,
      proliferation, and profiles of gene expression of various cell types after their
      exposure to nanofeatured materials are particularly reviewed. Finally, the paper
      briefly discusses some application of nanostructured materials including those in
      biosensor and tissue engineering fields.

PMID- 17025104
TI  - Advances in contemporary nanosphere lithographic techniques.
AB  - Nanosphere lithography (NSL) is an inexpensive, high throughput, materials
      general nanofabrication technique capable of producing a large variety of
      nanoscale structures including well-ordered 2 dimensional nanoparticle arrays. In
      this review, we will summarize the most recent advances in the fabrication of
      size-tunable nanoparticles using NSL. Four examples of new NSL-derived materials
      will be described: (1) The development of a method to release NSL nanoparticles
      from the substrate for applications in solution environments, (2) the fabrication
      of triangular nanoholes with reactive ion etching, (3) the electrochemical fine
      tuning of the structure of a silver nanoparticle and the wavelength of its
      localized surface plasmon resonance (LSPR), and (4) the growth of ultra thin
      protective dielectric layers on NSL-fabricated Ag nanotriangles using atomic
      layer deposition (ALD).

PMID- 17025105
TI  - Ozonolysis of functionalized single-walled carbon nanotubes.
AB  - Room temperature ozonolysis of fluorinated SWNT and phenyl-sulfonated SWNT have
      been studied in perfluoropolyether (PFPE) solvents. Etching at the end caps
      (approximately 70 nm/hour for fluorinated SWNT/PFPE suspension with 1 g/l
      concentration) has been demonstrated to be the dominating effect during the
      ozonolysis of fluorinated SWNT. Base on characterization by AFM analysis, X-ray
      Photoelectron Spectroscopy (XPS) and Raman Spectroscopy, fluorination along the
      SWNT sidewalls protects F-SWNT from extensive functionalization by ozonolysis. An
      ozone reaction with fluorinated SWNT has been found to improve its solubility in
      96% sulfuric acid. This allows oxidative cutting by ammonium peroxydisulfate
      without defluorination. In comparison to fluorinated SWNT, phenyl-sulfonated SWNT
      was found to be effectively and homogeneous cut by ozonolysis in a water
      suspension.

PMID- 17025106
TI  - Carbon nanotube based transparent conductive thin films.
AB  - Carbon nanotube (CNT) based optically transparent and electrically conductive
      thin films are fabricated on plastic substrates in this study. Single-walled
      carbon nanotubes (SWNTs) are chemically treated with a mixture of concentrated
      sulfuric acid and nitric acid before being dispersed in aqueous surfactant
      contained solutions. SWNT thin films are prepared from the stable SWNT solutions
      using wet coating techniques. The 100 nm thick SWNT thin film exhibits a surface
      resistivity of 6 kohms/square nanometer with an average transmittance of 88% on
      the visible light range, which is three times better than the films prepared from
      the high purity as-received SWNTs.

PMID- 17025107
TI  - Growth morphology and spectroscopy of multiwall carbon nanotubes synthesized by
      pyrolysis of iron phthalocyanine.
AB  - Carbon nanotubes (CNTs) were synthesized by Chemical Vapor Deposition (CVD) from
      the pyrolytic decomposition of Iron Phthalocyanine (FePc) molecules, on
      SiO2/Si(111) substrates in the presence of a hydrogen flow. FePc molecules
      contribute simultaneously both to the formation of the precursor Fe nanoparticles
      and also as a Carbon source. Different experimental conditions were examined.
      Samples were characterized by scanning electron microscopy, transmission electron
      microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and inverse
      photoemission. The resulting samples are highly oriented multiwall carbon
      nanotubes films, with heights in the range between: 4 and 20 microm. The tubes
      diameter is strongly dependent on growth temperature. Our experimental results
      show evidence of a transition in the growth mechanism, from a tip growth to a
      base growth mode, as the decomposition temperature is increased. Preliminary
      spectroscopic measurements performed on these MWCNTs, show the unoccupied density
      of states has several resonances close to Fermi level, related both to the
      graphene electronic structure and the formation of the tube.

PMID- 17025108
TI  - Fabrication and characterization of nanopore array.
AB  - A nanopore array with diameter of approximately 30 nm was fabricated by use of
      focused ion beam (FIB) scanning and thin film coating on Si(100). A thin film of
      SiO2 with thickness of 200 nm (used as sacrificial layer) was coated by physical
      evaporation deposition (PVD) first. Next, the thin films of Aluminum with
      thickness of 500 nm were coated on the surface of SiO2 thin film. A window with
      an area of 2 x 2 mm2 was opened by reactive ion etching from bottom side and
      reached to the thin film of SiO2. After that, a fine controlled FIB milling with
      bitmap function (milling according to a designed pattern in a defined area) was
      used to scan the area. Signal is obtained by a sensor inside the vacuum chamber
      collecting secondary electrons emitted from the sputtered material when the beam
      reach the layer of SiO2. Stopping the milling process at this moment, the
      nanopore array was derived after removing the sacrificial layer by wet chemical
      etching. The nanopore arrays were characterized using transmission electron
      microscopy (TEM) after the FIB drilling.

PMID- 17025109
TI  - Synthesis of ceramic nanoparticles by ultrafast laser ablation of solid targets
      in water.
AB  - We report production of nanoparticles of several advanced ceramics (Si3N4, SiC,
      AlN, and Al2O3) by ablation with femtosecond laser pulses of solid targets
      submerged in deionized water. The products withstand comparison with commercial
      nanoparticle suspensions obtained by other techniques as they are analyzed by
      means of transmission electron microscopy. As compared with metal nanoparticles
      produced with the same technique, we have found that the overall dependence of
      mean sizes and distribution widths on the laser fluence is similar. We explain
      why it is difficult to synthetize very small (<5 nm) and monodisperse particles
      in terms of ablation mechanism and discuss the aplicability of the technique for
      industrial production.

PMID- 17025110
TI  - Catalytic properties of silica/silver nanocomposites.
AB  - The catalytic properties of silver nanoparticles supported on silica and the
      relation between catalytic activity of silver particles and the support (silica)
      size are investigated in the present article. The silver nanoparticles with 4 nm
      diameters were synthesized and were attached to silica spheres with sizes of 40,
      78, 105 nm, respectively. The reduction of Rhodamine 6G (R6G) by NaBH4 was
      designed by using the SiO2/Ag core-shell nanocomposites as catalysts. The
      experimental results demonstrated that the catalytic activity of silica/silver
      nanoparticles depends on not only the concentration of catalysts (silver) but
      also the support silica size. Silver particles supported on small SiO2 spheres
      (approximately 40 nm) show high catalytic activity. Moreover, by making a
      comparison between the UV-vis spectra of the catalyst before and after the
      catalytic reaction, we found that the position of surface plasma resonance (SPR)
      peak of Ag nanoparticles changes little. The above results suggested that the
      size and morphology of silver particles were probably kept unchanged after the
      reduction of R6G and also implied that the catalytic activity of silver particles
      was hardly lost during the catalytic reaction.

PMID- 17025111
TI  - Spin transport in self assembled all-metal nanowire spin valves: a study of the
      pure Elliott-Yafet mechanism.
AB  - We report experimental study of spin transport in all metal nanowire spin valve
      structures. The nanowires have a diameter of 50 nm and consist of three layers-
      cobalt, copper, and nickel. Based on the experimental observations, we determine
      that the primary spin relaxation mechanism in the paramagnet layer--copper--is
      the Elliott-Yafet mode associated with elastic scattering caused by charged
      states on the surface of the nanowires. This mode is overwhelmingly dominant over
      all other modes, so that we are able to study the pure Elliott-Yafet mechanism in
      isolation. We deduce that the spin diffusion length associated with this
      mechanism is about 16 nm in our nanowires and is fairly temperature independent
      in the range 1-100 K, which is consistent with the spin relaxation being
      associated with elastic scattering by surface states. The corresponding spin
      relaxation time is about 100 femtoseconds. We also find that the spin relaxation
      rate is fairly independent of the electric field driving the current in the field
      range 0.3-3 kV/cm.

PMID- 17025112
TI  - Suppressing electrostatic screening in nanostructured electrode arrays.
AB  - An individual nanostructure provides very high electric field enhancement because
      the sharp curvature of the nanostructure tip amplifies the local electric field
      near the apex tip. However any practical nanostructured electrode is comprised of
      an ensemble (array) of nanostructures. In such systems, mutual electrostatic
      shielding (or screening) severely limits the maximum achievable electric field
      enhancement. In this paper, we discuss three approaches for suppression of
      shielding. These include--(1) reducing anode-to-cathode distance to less than the
      nanostructure-to-nanostructure spacing, (2) increasing length of selected
      individual nanostructures within the array, and (3) design of electrodes with
      multistage amplification. We show that these approaches are effective in
      alleviating electrostatic shielding and that the enhancement factor of the
      electrode array (ensemble) can be engineered to match that of the individual
      (isolated) nanostructure.

PMID- 17025113
TI  - Growth of aligned ZnO nanorods.
AB  - Growth of high-density and aligned ZnO nanorods on ZnO film substrate has been
      demonstrated using vapor-transport of thermally evaporated Zn metal powders
      followed by condensation. Morphological studies show that the nanorods grow
      preferentially from a hexagonal ZnO base with a uniform hexagonal structure
      following three-dimensional island-like growth mechanism. Structural and
      spectroscopic properties clearly indicate that the nanorods are relatively good
      and defect-free in quality. These nanorods have potential for technological
      implications.

PMID- 17025114
TI  - Nonlinear optical absorption and switching properties of gold nanoparticle doped
      SiO2-TiO2 sol-gel films.
AB  - The nonlinear optical absorption and switching properties of sol-gel derived of
      Au nanoparticle doped SiO2-TiO2 sol-gel films having different Au-surface plasmon
      absorption positions are reported in this paper. The Au nanoparticles are
      embedded in SiO2 and SiO2-TiO2 mixed glassy film matrices with different
      refractive index values. To study the nonlinear absorption properties, lasers
      with three different wavelengths are used. The optical switching behavior is
      studied by using the pump-probe technique with 532 nm as the excitation
      wavelength. Ground state conduction band, surface plasmon band, and the free
      carrier band are taken as three level model to explain theoretically the obtained
      RSA and SA behaviors.

PMID- 17025115
TI  - Versatile method for manipulating and contacting nanowires.
AB  - We present a simple, non-lithographic method for electrically connecting
      nanowires with electrodes on planar as well as non-planar microsystems. A rigid
      nanowire is used as a local shadow mask during deposition of metal contacts,
      which we use to contact structures of widely different conductances: Multiwalled
      carbon nanotubes, para-hexaphenylene nanofibers, as well as indium arsenide and
      indium phosphide nanowires. Finally we demonstrate how the method can be extended
      to different electrode materials on each side of the electrode gap, as well as
      for investigation of the electromechanical properties of a nanowire integrated in
      a cantilever.

PMID- 17025116
TI  - Structure and giant magnetoresistance behaviour of Co-Cu/Cu multilayers
      electrodeposited under various deposition conditions.
AB  - Electrodeposited Co-Cu/Cu multilayers were prepared under a variety of deposition
      conditions on either a polycrystalline Ti foil or on a silicon wafer covered by a
      Ta buffer and a Cu seed layer. X-ray diffraction (XRD) revealed a strong (111)
      texture for all multilayers with clear satellite peaks for the multilayers on
      Si/Ta/Cu substrates, in some cases for up to three reflections. Cross-sectional
      transmission electron microscopy investigations indicated a much more uniform
      multilayer structure on the Si/Ta/Cu substrates. The bilayer periods from XRD
      satellite reflections were in reasonable agreement with nominal values. An
      analysis of the overall chemical composition of the multilayers gave estimates of
      the sublayer thickness changes due to the Co-dissolution process during the Cu
      deposition pulse. The XRD lattice spacing data indicated a behaviour close to a
      simple "multilayer" Vegard's law which was, however, further refined by taking
      into account elastic strains as well. In agreement with the structural studies,
      magnetoresistance data also indicated the formation of more perfect multilayers
      on the smooth Si/Ta/Cu substrates. An analysis of the magnetoresistance behaviour
      revealed the presence of superparamagnetic (SPM) regions in the magnetic layers.
      The contribution of these SPM regions to the total observed giant
      magnetoresistance was found to be dominating under certain deposition conditions,
      e.g., for magnetic layer thicknesses less than 1 nm (about 5 monolayers).

PMID- 17025117
TI  - Synthesis of complex shape gold nanoparticles in water-methanol mixtures.
AB  - Gold nanoparticles with shapes which varied from spheres to multipods and
      polygons were prepared with a seedless approach in water/methanol mixtures in the
      presence of polyvinyl alcohol using sodium ascorbate as the reducing agent. The
      shape of Au nanoparticles is critically affected by the water/methanol ratio, as
      well as by the ratio of hydrogen tetrachloroaurate (HAuCl4) to sodium ascorbate
      and the concentration of HAuCl4 in the reaction mixture. A decreased ratio of
      water to methanol below 30/70 leads to the formation of multi-branched
      nanoparticles with the size in the range of 30-70 nm at relatively low HAuCl4
      concentration, whereas polygons are formed when HAuCl4 concentration increases.
      The polyvinyl alcohol stabilized multi-branched Au nanoparticle colloids were
      stable at room temperature for a period of at least six-month.

PMID- 17025118
TI  - Surface-initiated atom transfer radical polymerization of methyl methacrylate
      from magnetite nanoparticles at ambient temperature.
AB  - The synthesis of methyl methacrylate (MMA) brush from the surface of magnetite
      nanoparticles (core-shell structure), from initiator moieties anchored covalently
      to the nanoparticles, via room temperature atom transfer radical polymerization
      (ATRP) is described. The surface-initiated polymerization was carried out from a
      surface-confined initiator containing a 2-bromoisobutyrate moiety with
      Cu(I)Br/PMDETA catalytic system. The initiator moiety was covalently anchored to
      the nanoparticles via a two step modification reaction scheme. Controlled
      polymerization was observed if ethyl-2-bromoisobutyrate (2-EiBrB) was added as a
      free/sacrificial initiator. A linear increase of molecular weight and a narrow
      molecular weight distribution of the PMMA formed in solution, provide evidence
      for a controlled surface-initiated polymerization, leading to surface-attached
      polymer brushes under mild conditions. The grafted PMMA provides good stability
      and dispersibility for the nanoparticles in organic solvents.

PMID- 17025119
TI  - Deposition of metal nanoparticles on carbon nanotubes via hexane modified water
      in-CO2 microemulsion at room temperature.
AB  - Carbon nanotube-supported metallic nanoparticles (Pd, Rh, and bimetallic Pd-Rh)
      with diameters in the range 2-10 nm can be synthesized by hydrogen reduction of
      metal ions dissolved in the water core of a CO2 microemulsion in liquid CO2 at
      room temperature. The microemulsion is stabilized by sodium bis(2
      ethylhexyl)sulfosuccinate (AOT) and dissolved in liquid CO2 with the aid of
      hexane as a modifier. The metal nanoparticles synthesized in the microemulsion
      can be deposited on surfaces of multi-walled carbon nanotubes (MWCNTs) by
      stirring in the liquid CO2 phase. This simple method produces uniformly
      distributed metal nanoparticles on surfaces of the MWCNTs with high yields. The
      carbon nanotube-supported Pd/Rh bimetallic nanoparticles exhibit high catalytic
      activities for hydrogenation of aromatic compounds and can be reused without
      losing catalytic activity.

PMID- 17025120
TI  - Facile synthesis of Pt multipods nanocrystals.
AB  - A facile and efficient seeded growth approach was used to fabricate single
      crystal Pt multipods nanocrystals, which were intensively characterized by TEM,
      ED, HRTEM, XRD, EDX, and XPS. The size and shape of Pt multipod nanocrystals can
      be easily controlled by varying the ratio of Pt seeds to H2PtCl6. The catalytic
      performance of these nanocrystals as heterogeneous catalysts was examined using
      the hydrogenation of cyclohexene as a model reaction in a biphasic system. These
      Pt nanocrystals should have potential applications as catalysts in organic
      synthesis, electronics, sensors, and other devices.

PMID- 17025121
TI  - Effective band gap of Si nanocrystals embedded in SiO2 matrix.
AB  - Using a formulation of the Hartree-Fock formalism with the potential morphing
      method in the effective mass approximation, we calculate the effective band gap
      of Si nanocrystals embedded in SiO2 matrix without the existence of polysilane,
      as a function of their diameter in the size range 1-3.5 nm. Our results are in
      better agreement with the experimental data, in comparison with other existing
      theoretical data. For diameter smaller than 2 nm our results have the same
      tendency with the existing theoretical results, e.g., the discrepancy between
      theory and experiment seems to be essential.

PMID- 17025122
TI  - Formation of uniform single-crystalline bismuth sulfide nanowires under mixed
      solvent condition.
AB  - Uniform single-crystalline bismuth sulfide nanowires were prepared via a
      convenient solvothermal route under mixed-solvent condition. The nanowires were
      characterized by X-ray diffraction (XRD), high-resolution transmission electron
      microscopy (HRTEM), field-emission scanning electron microscopy (FESEM), energy
      dispersive X-ray (EDX) spectrometry and UV-vis spectrophotometer. The growth
      mechanism of the one-dimensional nanostructures was discussed. The optical
      absorption band gap of the nanowires is about 1.7 eV, and the blue-shift
      phenomenon can be observed with respect of that of the bulk Bi2S3, which might
      bring in new types of applications.

PMID- 17025123
TI  - Synthesis and mechanism study of mesoporous SnO2/SiO2 composites.
AB  - Mesoporous SnO2/SiO2 composite particles (Si/Sn < or = 0.25) sustainable to
      calcination up to 600 degrees C have been fabricated using a stepwise sol-gel
      technique on nonionic surfactant template (tetradecylamine, TDA). The newly
      designed preparation method involved the pre-formation of SnO2 sol solution from
      SnCl4. Subsequently, SnO2 nanocrystals were covered by the silicate species (from
      the hydrolysis of tetraethylorthosilicate, TEOS) in a pH controlled colloidal
      solution. Upon mixing with the surfactant solution, mesophase composite was
      obtained. After the removal of templates at various temperatures (400 to 600
      degrees C), worm-like mesoporous SnO2/SiO2 with large specific surface area and
      pore volume as high as 362 m2/g and 0.33 cc/g were obtained, respectively. High
      thermal stability is mainly due to the effective inhibition of SnO2 crystal
      growth (mean crystallite size <30 A) by the amorphous SiO2 species at the grain
      boundaries. Formation of mesoporous silicate skeleton such as M41S family
      material was prevented. The obtained materials maintain the relatively narrow
      pore size distribution typically in the range of 30 to 70 A. Relations between
      material properties and key synthesis parameters (i.e. TDA/Si/Sn molar ratio and
      calcination temperature) were investigated by TGA, wide/small-angle X-ray
      scattering, (HR)TEM, BET, and FTIR techniques. Mechanisms on the mesostructure
      formation and crystal growth inhibition were also proposed with detailed
      discussion.

PMID- 17025124
TI  - Rapid synthesis of cubic Pt nanoparticles and their use for the preparation of Pt
      nanoagglomerates.
AB  - We report the synthesis of hexadecyltrimethylammonium bromide (CTAB)-stabilized
      cubic Pt nanoparticles by NaBH4 reduction of H2PtCl6 in aqueous CTAB solution.
      These Pt nanoparticles (average size of 7 nm) were well dispersed in aqueous
      solution and stable at least for 2 months. Addition of a trace amount of AgNO3
      can alter the morphology of these Pt nanoparticles. More interestingly, the as
      prepared uniform Pt nanoparticles were further developed into bigger Pt
      nanoagglomerates (approximately 20 to 47 nm) by a seed-mediate growth process.
      Dentritic and spherical Pt nanoagglomerates can be synthesized by altering the
      incubation time and their size can be tuned by controlling the amount of the
      seeds added.

PMID- 17025125
TI  - Controllable synthesis of vertically aligned ZnO nanorod arrays in aqueous
      solution.
AB  - High-density well-aligned ZnO nanorod array was successfully synthesized on a
      large-area magnetron sputtering deposited Al doped ZnO film-coated Si (AZO/Si)
      substrate via a convenient solution method. X-ray diffraction and scanning
      electron microscopy show that the nanorods are well-oriented perpendicular to the
      substrate. The influences of the reaction temperature, time, on the size and
      shapes of the as-prepared ZnO nanorods (ZNs) samples have been studied. The
      length and diameter of the nanorods became bigger when a longer reaction time was
      used. When the temperature is elevated to 130 degrees C, a new conical ZNs was
      synthesized. Room-temperature photoluminescence (PL) spectra of all the ZnO
      products showed a strong ultraviolet (UV) emission. The photoluminescence from
      free excitons of the ZNs synthesized at higher temperature reflects the high
      purity and nearly defect free structure of nanorods. The well-aligned feature of
      the nanorod array is attributed to the nanorods' epitaxial growth from the AZO
      films.

PMID- 17025126
TI  - Electro-oxidation of methanol on TiO2 nanotube supported platinum electrodes.
AB  - TiO2 nanotubes have been synthesized using anodic alumina membrane as template.
      Highly dispersed platinum nanoparticles have been supported on the TiO2 nanotube.
      The supported system has been characterized by electron microscopy and
      electrochemical analysis. SEM image shows that the nanotubes are well aligned and
      the TEM image shows that the Pt particles are uniformly distributed over the TiO2
      nanotube support. A homogeneous structure in the composite nanomaterials is
      indicated by XRD analysis. The electrocatalytic activity of the platinum catalyst
      supported on TiO2 nanotubes for methanol oxidation is found to be better than
      that of the standard commercial E-TEK catalyst.

PMID- 17025127
TI  - Fabrication of polyethyleneimine and poly(styrene-alt-maleic anhydride) nanotubes
      through covalent bond.
AB  - Nanotubes of Polyethyleneimine (PEI) and Poly(styrene-alt-maleic anhydride)
      (PSMA) based on the layer-by-layer (LbL) technique and template method through
      covalent bond have been fabricated. The combination of LbL assembly and the
      template method can well control the length, wall thickness, outside, and inner
      diameters of the resulting nanotubes. The formation of covalent between PEI and
      PSMA enables the nanotubes with a good mechanical stability. The uniform tubular
      structure has been characterized by scanning electron microscopy (SEM) and
      transmission Electron Microscopy (TEM). Fourier transform infrared (FT-IR) and X
      ray photoelectron spectroscopy (XPS) measurements confirms the formation of
      covalent bond in the assembled nanotubes.

PMID- 17025128
TI  - Electric field modulation of infrared absorption at room temperature in
      electrochemically self assembled quantum dots.
AB  - We report observation of electric-field-modulated infrared absorption at room
      temperature in electrochemically self-assembled CdS quantum dots produced by
      electrodepositing the semiconductor in 50-nm pores of an anodic alumina film. The
      absorption is associated with photoassisted real space transfer of electrons from
      the CdS dots to surrounding trap sites in the alumina. Similar absorption was
      observed in the past [Appl. Phys. Lett. 79, 4423 (2001)] and was the basis of a
      room temperature near infrared photodetector. An electric field modulates this
      absorption by altering the overlap between the wavefunctions of electronic states
      in the quantum dots and the trap states in the surrounding alumina, thereby
      affecting the matrix element for radiative transitions, similar to the quantum
      confined Stark or Franz-Keldysh effect. The ability to electrically modulate
      absorption in these structures can result in inexpensive infrared signal
      processing devices operating at room temperature.

PMID- 17025129
TI  - Synthesis and characterization of monodispersed rhodium nanoparticles organized
      in 3-D symmetrical structures soluble in organic media.
AB  - Monodispersed rhodium nanoparticles were synthesized through a flexible and very
      simple approach in a monosurfactant system by thermolysis of RhCl3, in which
      oleyl amine serves as capping, reducing agent, and high boiled solvent. The
      coated rhodium nanoparticles are monodispersed with 4 nm diameter and well
      characterised by TEM microscopy, UV-Vis spectroscopy, and X-ray diffraction
      measurements. The as prepared rhodium nanoparticles have the tendency to
      aggregate forming well-organized large symmetrical and spherical 3-D
      superstructures which generally have diameters between 40-60 nm as revealed by
      the characteristic TEM images. Due to the organic monolayer that encloses the
      nanoparticles are soluble in non-polar organic solvents.

PMID- 17025130
TI  - Spiral growth of one dimensional titania nanostructures using anodic oxidation.
AB  - One dimensional spiral titania nanostructures were obtained by anodization of
      pure titanium from fluoride containing solutions of phosphoric acid. The
      formation of nanotubes was found to be dependant on current density. Field
      Emission Scanning Electron Microscopy (FESEM) shows the diameter of tubes around
      70-100 nm which is consistent with the High Resolution Transmission Electron
      Micrographs (HRTEM) and Atomic Force Microscopy (AFM) images. HRTEM showed the
      one dimensional growth as spiral in nature which was also supported by AFM
      images. This anisotropic growth is compared with the possible growth mechanisms.

PMID- 17025131
TI  - Growth of zinc oxide nanorods, tetrapods, and nanobelts without catalyst.
AB  - Zinc oxide (ZnO) nanostructures with various morphologies have been synthesized
      without catalyst in a one-step simple redox process. The results show that ZnO
      nanorods, nanobelts, and tetrapods with hexagonal needled arms could be
      synthesized via thermal treatment of a mixture of zinc oxide and charcoal powder
      in a muffle furnace at 1000-1200 degrees C for 240 min. XRD analyses showed that
      polycrystalline ZnO phase with wurtzite crystal structure was formed. At a
      relatively low temperature, 1000 degrees C, the ZnO structure was found to be a
      bundle of denser nanorods. By increasing the reaction temperature to 1100 degrees
      C, tetrapod-like structures of needle-like arms with pyramidal tips were formed.
      With the increase of temperature up to 1200 degrees C, the morphology of ZnO
      nanostructures changed from nanorods and tetrapods to coalescence grains.
      Reaction temperature was found to be the most important experimental parameter
      that played an important role in controlling the mode, mechanism of growth, and
      formation of different ZnO morphologies.

PMID- 17025132
TI  - Direct synthesis of nanocrystalline silver from the reaction between silver
      carboxylates and n-trioctylphosphine.
AB  - Neat n-Trioctylphosphine (TOP) has been used for the first ever time for
      reduction of silver nitrate and silver carboxylates (citrate, oleate, and
      myristate) under mild thermal reaction conditions. UV-visible absorption
      measurements of re-dispersible silver particles that were obtained by reduction
      of silver myristrate (product-IV) and silver nitrate (product-I) showed surface
      plasmon resonance absorption peak at 400 nm. The powder XRD pattern of fcc zero
      valent silver resulted in diameters in the range of about 25-30 nm. TEM analysis
      showed particle diameter similar to that was observed by the XRD. FTIR
      spectroscopy revealed that the organics from the carboxylate group are retained
      by the nano-particles in case of product-IV however, presence of TOP is observed
      in product-I. It is found that when silver nitrate is reduced by TOP, spherical
      silver nano-particles with poor redispersity are formed but extended heating
      results in formation of long silver rods of micrometer size however, the re
      dispersible nano-particles are easily formed when silver carboxylates are reduced
      by TOP.

PMID- 17025133
TI  - Synthesis and characterisation of YSZ-Al2O3 nanostructured materials.
AB  - In this work a co-precipitation route was used to synthesise two yttria
      stabilised-zirconia (YSZ) phases with different concentrations of alumina
      (Al2O3). A tetragonal, with 3 mol% yttria, and a cubic, with 8 mol% yttria,
      phases were added with alumina in different weight proportions, 90/10, 80/20,
      70/30, and 60/40, respectively. After synthesised, products were sintered in a
      range 800-1100 degrees C for different intervals of time. Compounds were
      characterised by X-ray diffraction, transmission electron microscopy (TEM), high
      resolution transmission electron microscopy (HRTEM), scanning electron microscopy
      (SEM), and atomic force microscopy (AFM). Rietveld refinements, using FULPROF
      Suite software, were carried out to obtain the cell parameters and structural
      characterisation of products.

PMID- 17025134
TI  - Synthesis of nanostructured bismuth titanate microspheres.
AB  - A hydrothermal method was developed for the synthesis of bismuth titanate
      nanostructured microspheres. The precursor powder was prepared using a diethylene
      glycol mediated coprecipitation method. The as-synthesized nanostructured
      microspheres consisting of granular nanoparticles and nano-platelets were
      obtained through a hydrothermal treatment of the precursor powder in aqueous
      sodium hydroxide solution. Tailoring of the morphology was achieved by changing
      the precursor quantity, sodium hydroxide concentration, and reaction time. The
      formation mechanism of the nanostructured microspheres probably involves
      aggregation, followed by dissolution and recrystallization. X-ray diffraction,
      scanning electron microscopy and energy dispersive X-ray spectroscopy were used
      to characterize the phase purities, morphologies, and composition of the
      products.

PMID- 17025135
TI  - Electrochemical behavior of alpha-MoO3 nanorods as cathode materials for
      rechargeable lithium batteries.
AB  - The electrochemical properties of alpha-MoO3 nanorods, which were synthesized via
      a solution-based method and following calcination, have been reported as a
      cathode material for rechargeable lithium batteries. Detailed lithium-insertion
      process of the material has been conducted by means of cyclic voltammetry,
      galvanostatic method, and impedance technique, and superior features associated
      with the nanostructures have been observed. The alpha-MoO3 nanorods exhibited an
      initial discharge capacity of 271.8 mAh/g under a current density of 0.1 mA/cm2
      in the range 1.0 approximately 3.0 V, which nearly approached the theoretical
      capacity 280 mAh/g. Comparison of the structural and electrochemical
      characteristics with those of bulk alpha-MoO3 suggests the enhanced
      electrochemical performance might be related to the rodlike structure and
      increased edge and corner effects.

PMID- 17025136
TI  - Microemulsion-mediated solvothermal synthesis and morphological evolution of
      MnCO3 nanocrystals.
AB  - The morphology- and size-controlled synthesis of MnCO3 nanocrystals was
      successfully achieved by cationic surfactant-CTAB-microemulsion-mediated
      solvothermal method. Various comparison experiments with different reactant
      concentrations and molar ratios between water and CTAB, showed the evolvement law
      of the morphology and size of the as-synthesized MnCO3 nanocrystals. With slowly
      increasing the concentration of reactants and/or molar ratio between water and
      CTAB, the morphology of MnCO3 nanocrystals changed gradually from cube to
      parallelepiped, and then rhombohedron, whereas the size decreased a little. The
      effect of the experimental parameters on the shapes and sizes of samples, such as
      the source of carbonate salts, reaction time, and temperature, were also
      discussed. X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), selected area electron diffraction (SAED), and high-resolution
      transmission electron microscopy (HRTEM) were used to characterize the products.

PMID- 17025137
TI  - Morphological modifications of selenium by recrystallization of its aqueous
      complex solutions.
AB  - Recrystallization of elemental selenium (Se) from aqueous solution in presence of
      sodium sulphite (Na2SO3) and sodium sulphide (Na2S) acting as complexing agents
      has resulted in the formation of nano and microstructures of Se having five
      different morphological modifications. (1) An aqueous solution of sodium
      selenosulphate (Na2SO3Se) obtained by dissolving Se in Na2SO3 under refluxing
      condition yields hemispherical microcrystals. (2) The filtrate of the above
      reaction mixture on aging produces hexagonal prismatic microrods of Se. Addition
      of Na2SO3Se solution to formalin (HCHO) at room temperature and refluxing
      conditions generates (3) Se nanorods, and (4) spherical microcrystals,
      respectively. (5) Recrystallization of Se from aqueous solution of Na2S develops
      flower shaped microcrystals.

PMID- 17025138
TI  - Synthesis of monodisperse iron oxide and iron/iron oxide core/shell nanoparticles
      via iron-oleylamine complex.
AB  - Monodisperse magnetic nanoparticles are of great scientific and technical
      interests. This paper reports a single-step synthesis of monodisperse magnetite
      nanoparticles with particle size of 8 nm. Iron/maghaemite core/shell
      nanoparticles with particle size of 11 nm were obtained by reducing the
      concentration of oleylamine. TEM and in-situ FTIR results suggested that iron
      oleylamine intermediate was generated in-situ and decomposed at higher
      temperature. Oleylamine was also found on the surface of nanoparticles,
      indicating its role as capping agent which provided steric protection of as
      synthesized nanoparticles from agglomeration. Both magnetite and iron/maghaemite
      core/shell nanoparticles were superparamagnetic at room temperature with a
      blocking temperature at 80 K and 67 K, respectively.

PMID- 17025140
TI  - Effect of sintered grain growth on chemical ordering in binary FePt/Cu
      nanoparticle arrays.
AB  - Recent studies have shown a strong correlation between grain growth and chemical
      ordering in chemically synthesized FePt nanoparticles. In order to study this
      effect, we have prepared a series of samples in which 3.5 nm FePt nanoparticles
      are dispersed in a matrix of Cu nanoparticles. The samples were annealed at 600
      degrees C and at 800 degrees C. Grain size was determined by XRD Scherrer
      analysis and time-dependent remanent coercivity measurements were made to
      determine the intrinsic remanent coercivity, Hcr0. For samples annealed at 600
      degrees C, Hcr0 increases strongly with grain size up to approximately 5 nm and
      increases weakly with additional grain growth. By contrast, after annealing at
      800 degrees C, Hcr0 appears nearly independent of grain size. The results suggest
      that isolated 3.5 nm FePt nanoparticles can be weakly ordered when annealed at
      600 degrees C and sintering is necessary for significant chemical ordering.

PMID- 17025139
TI  - Tuned optical properties of in-situ synthesized m-nitroaniline doped Ag/PVA nano
      composites.
AB  - Meta-nitroaniline (m-NA) doped silver/poly(vinylalcohol) (Ag/PVA) nanocomposites
      are prepared via in-situ reduction of silver salt by employing hydrazine hydrate
      (HH) in order to study the effect of the NLO active m-NA on the optical
      properties of nanoparticles of silver in the colloidal as well as self supported
      film form. Reduction of silver salt in aqueous alcoholic PVA with HH is done
      first followed by doping of the reaction mixture with m-NA. The UV-Visible
      absorption spectra show peak at about 400 nm for Ag nanoparticles due to surface
      plasmon resonance phenomenon, which gets blue shifted with the change in m-NA
      concentration. The Second Harmonic Generation (SHG) studies show improvement in
      intensity with increasing m-NA concentration up to a saturation point
      (approximately 2.52 wt% with respect to PVA). Further increase in m-NA
      concentration leads to decrease in SHG intensity. The solutions and the films are
      characterized by photoluminescence (PL), FTIR spectroscopy, XRD, SEM, TEM, and
      thermal analysis. m-NA doped composites showed better PL efficiency. SEM of the
      nanocomposite film shows uniform distribution of particles within the film. The
      particle size as shown by TEM is found to be less than 10 nm.

PMID- 17025141
TI  - Relevant features of bentonite modification with a phosphonium salt.
AB  - Nanoclays with high decomposition temperatures were prepared for the first time
      with a new synthesized triphenyl-vinylbenzyl-phosphonium chloride modifier which
      is reactive with vinyl monomers and easy to remove from clay surface.

PMID- 17025142
TI  - Synthesis and characterization of uncapped gamma-Fe2O3 nanoparticles prepared by
      flame pyrolysis of ferrocene in ethanol.
AB  - Nanoparticles of iron(III) oxide were synthesized by spontaneous combustion of
      ferrocene in ethanol solution using a simple spirit lamp. X-ray powder
      diffraction and electron diffraction analysis of the powder suggested the
      formation of gamma-Fe2O3 (Maghemite phase) having lattice constant 8.3539 +/-
      0.0209 A. Transmission Electron Micrograph suggested the formation of spherical
      particles with an average diameter of 24.7 +/- 1.6 nm. A sextet with an isomeric
      shift of 0.328 mm s(-1) seen in the Mossbauer spectrum recorded at room
      temperature, further supports the formation of gamma-Fe2O3. The particles were
      dispersed freely in the polar solvents like ethanol, dimethyl sulfoxide, and
      water. Infra Red spectrum gave bands at 400, 432, 565, and 638 cm(-1), which
      confirms the presence of gamma-Fe2O3 phase.

PMID- 17025143
TI  - Chirality dependence of carbon single-walled nanotube material properties: axial
      Young's modulus.
AB  - The potential use of individual carbon nanotubes as nano devices warrants
      detailed investigation of their mechanical behavior based on structural and
      geometrical configurations. The objective of this paper is to unravel the
      structural and chirality dependence of the axial Young's modulus of a carbon
      single-walled nanotube by analytical and numerical approaches. In this work, we
      employ the general homogenization composite shell model developed based on the
      asymptotic homogenization technique for analytical modeling of single-walled
      nanotubes. We derive the working formulae for the effective elastic properties of
      carbon single-walled nanotube of any chirality and predict the structural and
      chiral dependence of the effective axial Young's modulus of the nanotube. Also, a
      finite element analysis on the chirality dependence of the axial Young's modulus
      of the carbon nanotube is reported. The outcomes of our analyses are compared
      with available experimental and simulation results.

PMID- 17025144
TI  - Chirality dependence of carbon single-walled nanotube material properties: axial
      coefficient of thermal expansion.
AB  - Carbon nanotubes are one of the best candidates for applications where
      structural, thermal, and chemical stabilities are of great importance. Despite
      the fact that significant efforts have been devoted to study properties and
      behavior of the carbon nanotubes in recent years, there have not been sufficient
      results available on their thermoelastic properties. This paper investigates the
      chirality dependence of coefficient of thermal expansion of carbon single-walled
      nanotubes both analytically and numerically. The analytical approach in
      characterizing the chirality dependence of the coefficient of thermal expansion
      uses an asymptotic homogenization method. A second analytical interpretation
      follows a free-expansion strain method based on basic principles of
      thermoelasticity. The derived formulae make it easy to understand the
      dependencies of the nanotube thermoelastic properties on its geometrical
      parameters. The results from these analytical studies were verified using a
      finite element method. All three independent studies consistently demonstrate
      that the coefficient of thermal expansion of carbon single-walled nanotubes is
      independent of their chirality.

PMID- 17025145
TI  - Fabrication of nanopores in a 100-nm thick Si3N4 membrane.
AB  - Textured alumina films have been used to fabricate nanoscale pores in Si3N4
      membranes. A few nanometer-thick alumina layer was used as a masking material for
      nanopore fabrication, and the pattern was transferred into a 100-nm thick, 200
      microm x 200 microm Si3N4 membrane by reactive ion etching (RIE). The nanopores
      were found to be concentrated in a approximately 150-microm diameter region at
      the center of the membrane.

PMID- 17025146
TI  - Structural and optical characterization of strained free-standing InP nanowires.
AB  - The structural and optical properties of high-quality crystalline strained InP
      nanowires are reported in this article. The nanowires were produced by the vapor
      liquid-solid growth method in a chemical-beam epitaxy reactor, using 20 nm gold
      nanoparticles as catalysts. Polarization-resolved photoluminescence experiments
      were carried out to study the optical properties of the InP nanowires. These
      experiments revealed a large blue shift of 74 meV of the first electron-to-heavy
      hole optical transition in the nanowires, which cannot be solely explained by
      quantum size effects. The blue shift is mainly attributed to the presence of
      biaxial compressive strain in the inward radial direction of the InP nanowires.
      High-resolution transmission electron microscopy Electron and selected area
      electron diffraction experiments show that the nanowires have high crystal
      quality and grow along a [001] axes. These experiments also confirmed the
      presence of 1.8% compressive radial strain and 2% tensile longitudinal strain in
      the nanowires. A simple theoretical model including both quantum confinement and
      strain effects consistently describes the actual energy position of the InP
      nanowires optical emission.

PMID- 17025147
TI  - Novel DNA nano-patterning design method utilizing poly-L-lysine patterning by
      nanoimprint lithography.
AB  - The DNA properties have been deliberated to comprehend new functional bio
      devices. However there are few reports on DNA nano-patterning to make them.
      Therefore, we have tried DNA nano-patterning by using a nanoimprint process. A
      substrate coated with a poly-L-lysine was heated at 120 degrees C for 5 min in
      atmosphere, and nanoimprint carried out at 120 degrees C, 6 MPa, 5 min, and we
      applied 1 mg/ml DNA solution on the substrate and immobilized with the poly-L
      lysine. Finally the substrate was washed at twice in water and at once in hot
      water intensely. DNA lines that consist of lines at about 700 nm as line width
      was obtain, and the very fine lines correspond to convex patterns of the mold
      surface. These results suggest that the imprint would make the poly-L-lysine
      reform by exposing it under high pressure and high temperature. Therefore since
      DNA is immobilized with the amino group in the poly-L-lysine, a lot of amino
      group would expose on the surface by the imprint from the balk, and would be
      patterned DNA.

PMID- 17025148
TI  - Dispersion of multi-walled carbon nanotubes in biodegradable poly(butylene
      succinate) matrix.
AB  - This communication describes the preparation, characterization and properties of
      biodegradable poly(butylene succinate) (PBS)/multi-walled carbon nanotubes
      (MWCNTs) nanocomposite. Nanocomposite was prepared by melt-blending in a batch
      mixer and the amount of MWCNTs loading was 3 wt%. State of dispersion
      distribution of the MWCNTs in the PBS matrix was examined by scanning and
      transmission electron microscopic observations that revealed homogeneous
      distribution of stacked MWCNTs in PBS matrix. The investigation of the
      thermomechanical behavior was performed by dynamic mechanical thermal analysis.
      Results demonstrated substantial enhancement in the mechanical properties of PBS,
      for example, at room temperature, storage flexural modulus increased from 0.64
      GPa for pure PBS to 1.2 GPa for the nanocomposite, an increase of about 88% in
      the value of the elastic modulus. The tensile modulus and thermal stability of
      PBS were moderately improved after nanocomposite preparation with 3 wt% of
      MWCNTs, while electrical conductivity of neat PBS dramatically increased after
      nanocomposite formation. For example, the in plane conductivity increased from
      5.8 x 10(-9) S/cm for neat PBS to 4.4 x 10(-3) for nanocomposite, an increase of
      10(6) fold in value of the electrical conductivity.

PMID- 17025149
TI  - High throughput growth of zinc oxide nanowires from zinc powder with the
      assistance of sodium chloride.
AB  - Sodium chloride (NaCl) was found to be very helpful in producing single crystal
      zinc oxide (ZnO) nanowires in gram quantities. The growth involves heating the
      mixture of zinc powder and NaCl to 600-700 degrees C in flowing gases of oxygen
      and argon. A conversion efficiency of 70-80% (Zn to ZnO) was achieved when NaCl
      was used, and 5-10% without NaCl. The NaCl was completely removed by soaking and
      rinsing the mixture in water a few times. Photoluminescence spectra using
      excitation of 325 nm showed a very strong emission only in the visible frequency
      range, indicating that the surface states dominate the emission.

PMID- 17025150
TI  - Transmission electron microscopy investigation of Sb-doped ZnO nanoribbons and
      Zn7Sb2O12 branched ZnO nanoribbon structure.
AB  - Sb-doped ZnO nanoribbons have been synthesized by simple thermal evaporation of
      powder mixtures of Zn and Sb2O3. The Sb-doped ZnO nanoribbons with hexagonal
      wurtzite structure have a growth direction of [0110], widths of 100-300 nm, and
      lengths up to several hundreds of micrometers. The atomic ratio of Sb and Zn is
      about 1:40 by energy dispersive X-ray spectroscopy measurement. A stripe contrast
      is found in the center of the Sb-doped ZnO nanoribbon, which is speculated to be
      due to the enrichment of Sb in the center of the Sb-doped ZnO nanoribbon by
      energy dispersive X-ray spectroscopy line scanning element mapping. Furthermore,
      a novel Zn7Sb2O12 branched ZnO nanoribbon structure is investigated. The growth
      direction of the branch and the backbone are [211] and [0110], respectively. The
      mechanisms of formation of such nanomaterials are also discussed.

PMID- 17025151
TI  - Carbon nanotube--poly(3-octylthiophene) composite photovoltaic cells.
AB  - The effects of varying nanotube loading/concentration in carbon nanotube-poly(3
      octylthiophene) blends used as thin film photovoltaic cells, have been studied.
      The network of single walled nanotubes clearly aids in exciton separation and
      modifies carrier mobility within the active layer as suggested by a bulk
      heterojunction model. Further, modifications to the metal-polymer interface occur
      with the addition of nanotubes leading to variations in the observed VOC of the
      photovoltaic cells. Finally, the "nanocomposite" devices exhibit significant
      enhancements to external power conversion efficiencies, with the overall
      efficiency strongly dependent on device design parameters such as the addition of
      buffer layers.

PMID- 17025152
TI  - [Contribution of the SuUR gene to the organization of epigenetically repressed
      regions of Drosophila melanogaster chromosomes].
AB  - A significant portion of a eukaryotic genome is silent (epigenetically
      repressed). In Drosophila melanogaster, this portion includes mainly regions of
      pericentric and intercalary heterochromatin and euchromatin regions subject to
      position-effect variegation. Detailed study of the organization of intercalary
      heterochromatin regions of Drosophila melanogaster polytene chromosomes started
      from the discovery of the SuUR gene (Suppressor of UnderReplication). The ability
      of the SuUR mutation to suppress underreplication in intercalary heterochromatin
      regions was used for molecular tagging of these regions. We showed that
      underreplicated intercalary heterochromatin regions contained silent unique genes
      and retained the features of late replication and transcriptionally inactive
      chromatin state in various cell types. Over 50% of these regions contain unique
      genes clustered on the base of coordinated expression. The origin of clusters and
      putative mechanisms of their gene expression are discussed. Data on the SuUR
      gene, its expression, and effect on polytene chromosome structure and replication
      are summarized.

PMID- 17025153
TI  - [Insulators of higher eukaryotes: properties, mechanisms of action, and role in
      transcriptional regulation].
AB  - One of the dogmas of transcriptional regulation in higher eukaryotes suggests the
      existence of transcriptional domains with no promoter-enhancer interactions
      between them. Specific regulatory elements, known as insulators, block the
      interaction between an enhancer and a promoter. Insulators are believed to act as
      transcription domain boundaries. The review considers general properties of well
      known insulators identified in Drosophila and vertebrates. The mechanism of
      action of insulators and their role in the regulation of gene expression are
      discussed on the basis of available information.

PMID- 17025154
TI  - [Molecular genetics of Parkinson's disease].
AB  - The current views on the role of genetic factors in the pathogenesis of
      Parkinson's disease are considered. The review is focused on monogenic forms of
      the disease, for which 11 loci are mapped and seven genes whose mutations cause
      the disease are identified. In addition, a number of candidate genes for sporadic
      Parkinson's disease are described. The further development of studying genetic
      bases of Parkinson's disease will follow two main directions: in-depth analysis
      of genes related to the monogenic form of the disease and more large-scale
      associative investigation of candidate genes for the sporadic form of Parkinson's
      disease.

PMID- 17025155
TI  - [Expression of drgA gene encoding NAD(P)H:quinone-oxidoreductase in cells of the
      cyanobacterium Synechocystis sp. PCC 6803].
AB  - The gene drgA of the cyanobacterium Synechocystis sp. PCC 6803 encoding soluble
      NAD(P)H:quinone-oxidoreductase is involved in NADPH oxidation and controls cell
      sensitivity to nitroaromatic inhibitors as well as resistance to the oxidative
      stress inducer menadione. The expression of drgA was analyzed by means of
      Northern blot hybridization and RT-PCR technique. Two transcripts, which gave a
      positive hybridization signal with a drgA probe were observed in
      photoautotrophycally grown cells. One of them (0.6 kb) corresponds in size to
      mRNA read from the drgA gene; another transcript (1.3 kb), to mRNA transcribed
      from two genes: drgA and slr1718 located upstream of drgA and having homology
      with genes of the family comB. The expression of genes drgA and slr1718 was
      repressed during cell incubation in the dark, but the addition of glucose led to
      a drastically enhanced expression both in the dark and after illumination of
      cells. Menadione or nitrophenolic herbicide dinoseb did not induce drgA or
      slr1718 expression. The results obtained suggest that the expression of these
      genes in the cytoplasm of cyanobacterium cells is regulated by the NADPH content.

PMID- 17025156
TI  - [Comparison of new giant bacteriophages OBP and Lu11 of soil pseudomonads with
      bacteriophages of phiKZ-supergroup of Pseudomonas aeruginosa].
AB  - Study of two recently isolated giant bacteriophages Lu11 and OBP that are active
      on Pseudomonas putida var. Manila and Pseudomonas fluorescens, respectively,
      demonstrated their similarity in morphology, genome size, and size of phage
      particles, with giant bacteriophages of Pseudomonas aeruginosa assigned to the
      supergroup of phiKZ-like phages of the family Myoviridae designated in this
      manner according to the best studied phage phiKZ that belongs to the species of
      this group widely distributed in nature. Comparison of major polypeptide sizes of
      mature particles suggests the similarity of certain proteins in the phages
      examined. In OBP particles visualized with an electron microscope, an "inner
      body" was detected, which points to the specific DNA package intrinsic to phages
      of phiKZ group. In the meantime, phages Lul11 and OBP do not exhibit resemblance
      among themselves or with any of earlier described phiKZ-like phages in respect to
      other traits; particularly, they have no detectable DNA homology. Note that phage
      Lu11 of P. putida var. Manila exhibits very slight homology with phage Lin68 of
      the family of P. aeruginosa phiKZ-like phages detected only in blot
      hybridization. This suggests the possible involvement of these phages in
      interspecies recombination ("gene shuffling") between phages of various bacterial
      species. Results of partial sequencing of phage genomes confirmed the
      phylogenetic relatedness of phage OBP to phages of the phiKZ-supergroup, whereas
      phage Lu11 most probably belongs to a novel species that is not a member of
      supergroup phiKZ composition. The results of the study are discussed in terms of
      the evolution of these phages.

PMID- 17025157
TI  - [Cloning the amidase gene from Rhodococcus rhodochrous M18 and its expression in
      Escherichia coli].
AB  - The amidase gene from Rhodococcus rhodochrous M18 was cloned by PCR amplification
      with primers developed by use of peptide amino acid sequences obtained after
      treating amidase with trypsin. Nucleotide sequence analysis of this gene revealed
      high homology with aliphatic amidases from R. erythropolis R312 and Pseudomonas
      aeruginosa. Considering the substrate specificity and the results of DNA
      analysis, amidase from R. rhodochrous M8 was assigned to the group of aliphatic
      amidases preferentially hydrolyzing short-chain aliphatic amides. The amidase
      gene was expressed in cells of Escherichia coli from the self promoter and from
      the lac promoter. To clone a fragment of R. rhodochrous M8 chromosome
      (approximately 9 kb), containing the entire structural gene and its flanking
      regions, plasmid pRY1 that can be integrated into the chromosome via homology
      regions was used. No sequences of the nitrile hydratase gene, the second key gene
      of nitrile degradation in strain R. rhodochrous M8, were detected. Thus, genes
      encoding amidase and nitrile hydratase in strain R. rhodochrous M8 are not
      organized into a single operon despite their common regulation.

PMID- 17025158
TI  - [In planta transformation of maize through inoculation of Agrobacterium into the
      silks].
AB  - Integration of T-DNA into the maize genome as a result of treatment of silks with
      Agrobacterium cells, containing activated vir genes, was demonstrated. In planta
      treatment of maize (Zea mays L) was performed during flowering in field. Cell
      suspension of Agrobacterium tumefaiciens strain GV3101(pTd33), carrying activated
      vir genes, was applied onto the previously isolated silks, which were afterwards
      pollinated with the pollen of the same cultivar. Integration of T-DNA into maize
      genome was confirmed by PCR (the nptII and gus reporter genes) and hystochemical
      staining of the seedling tissues, obtained from the transformed seeds.
      Amplification of the nptII gene showed the presence of about 60.3% of PCR
      positive plants out of the total number of kanamycin-resistant seedlings
      examined, or 6.8% of the total of number of seedlings.

PMID- 17025159
TI  - How to map ses, a mutant of Arabidopsis thaliana affecting pollen development.
AB  - In Arabidopsis, map-based cloning has been developed to an effective method in
      mutant genetic analysis because high-density markers are available, candidate
      genes or genomic sequences can be amplified by PCR and transgenic techniques are
      simplified. Mutant ses named from shortened early-stage siliques was used as an
      example to show how to map a mutant in this day. By the process of bulked
      segregants analysis, linkage testing, large-scale and fine scale mapping, mutant
      ses was narrowed into a 67 kb interval from CER448792 (2000541 bp) to CER464544
      (2067844 bp) crossing over the right of BAC F12K11 to the left of the BAC F4H5
      including at most 22 putative genes on the top of chromosome l. In sequence-based
      map of Arabidopsis genes with Mutant phenotype (SMAGMP) mutant ses was between
      ATlg06150 (EMB1444) and ATlg08060 (MOM). The SES mapping also showed that
      developed markers on polymorphism site of CAPC not only were simplified and but
      worked well. 24 markers from CAPC used in the mapping maybe help Arabidopsis
      researches with others and the methods related to SES mapping also gave an
      example of positional cloning.

PMID- 17025160
TI  - [Genealogical analysis of resistance to fusarium head blight in Russian and
      Ukrainian cultivars of common wheat Triticum aestivum L].
AB  - The GRIS3.5 information analytical system of wheat genetic resources was used to
      track the possible ways of the transmission of fusarium head blight resistance
      from ancestors to progenies in extended pedigrees of 149 Russian and Ukrainian
      cultivaris of winter common wheat. Analysis of variance was performed for the
      coefficient of parentage computed for the cultivars under study and the putative
      sources of resistance and revealed that groups of resistant and susceptible
      cultivars differed in the distribution of contributions of the sources. In the
      resistant group, significant results were obtained for the contributions of
      Odesskaya 16, Gostianum 237, and Frontana. Pedigree analysis showed that fusarium
      head blight resistance was most commonly transmitted from Gostianum 237 through
      Odesskaya 16 and its derivatives. The landrace Khar'kovskaya probably served as a
      source of resistance in the case of Gostianum 237. In addition, the set of
      resistance sources included Kooperatorka, Hope, San Pastore, Triticum timopheevii
      Zhuk., and Secale cereale. Some well-known sources of fusarium head blight
      resistance varying in genetic determinants--Sumai 3, Wangshuibai, Wuhan 1, Nyubay
      (China), Nobeokabozukomugi, Shinchunaga (Japan), Arina (Switzerland), Fundulea
      201R (Romania), and Renan (France)--have so far not being employed in breeding in
      Russia and provide an important reserve for breeding for resistance.

PMID- 17025161
TI  - [A comparison of two existing catalogues of the alleles of gliadin-coding loci in
      winter common wheat].
AB  - Two catalogs of alleles of gliadin-coding loci, controlling synthesis of a
      storage protein of wheat caryopsis, gliadin, were compared. One catalogue
      comprises the alleles detected according to the electrophoretic patterns in
      starch gels; the other, in polyacrylamide gels. Determination of the allelic
      state of gliadin-coding loci in 31 previously not studied cultivars of winter
      common wheat allowed us to construct a matching system for the alleles compiled
      in the two catalogs, which gives the possibility to compare the results of wheat
      cultivar analyses performed at different scientific institutions.

PMID- 17025163
TI  - [Genetic diversity and differentiation of Russian common carp (Cyprinus carpio
      L.) breeds inferred from RAPD markers].
AB  - Polymorphic components of the common carp Cyprinus carpio L. genome were examined
      by means of polymerase chain reaction with random primers (RAPD-PCR). Using four
      primers, genetic diversity estimates were obtained for 12 populations and seven
      strains of Russian common carp breeds, as well as for European Hungarian common
      carp and Amur wild common carp (N = 87). The highest number of polymorphic loci
      was revealed in Angelinskii common carp, as well as in the samples of Altai
      common carp and Amur wild common carp (P = 23.8-18.7%), while the lowest number
      of polymorphic loci was in the BB strain of Ropsha common carp. The index of
      genetic diversity, H, was high (11%) in Amur wild common carp, as well as in
      Altai and Angelinskii common carps. In the remaining breeds, the value of this
      index varied from 4 to 8%. Based on summarized RAPD profile (132 bands), a
      dendrogram of genetic differences was constructed. In this dendrogram, all breeds
      examined grouped into two clusters. One of the clusters was formed by Hungarian
      and Angelinskii common carps, and the three samples of Altai common carp. The
      second cluster was formed by the group consisting of the representatives of
      Cherepetskskii, Stavropol, and Ropsha common carps, along with the differing from
      them Amur wild common carp. The observed differentiation was confirmed by the
      analysis of the polymorphic markers variance by the method of principle
      components. Evolutionary history and the reasons for genetic differentiation of
      Russian common carp breeds are discussed.

PMID- 17025162
TI  - Single nucleotide polymorphism in the promoter region of the lactoferrin gene and
      its associations with milk performance traits in Polish Holstein-Friesian cows.
AB  - Bovine lactoferrin (LTF) is a multifunctional small glycoprotein found in milk
      acting mainly as a defense factor in the mammary gland. Many polymorphisms have
      been found in the bovine LTF gene but almost none were considered as genetic
      markers of production traits in dairy cattle. In this study, the promoter
      fragment of LTF gene containing mutation (G/C) in position +32 has been amplified
      by PCR followed by genotyping by the SSCP and RFLP method. 358 Polish Holstein
      Friesian cows were screened, giving the following frequency of genotypes: 0.628,
      0.313 and 0.059 for GG, GC and CC, respectively. GLM (General Linear Model)
      analysis was applied to evaluate the associations of lactoferrin with milk
      performance traits, including SCC - somatic cell count. It was found that CC cows
      show significantly higher (P < or = 0.01) protein content in milk in comparison
      with GG cows. The values of other milk performance traits were also higher but at
      non-significant levels. SCC in milk was the lowest in CC cows, but also at a non
      significant level.

PMID- 17025164
TI  - [Types of Y chromosome deletions and their frequency in infertile men].
AB  - Deletions of Y chromosome AZF locus were analyzed during a large-scale
      andrological and genetic examination of 810 infertile men. The search for Yq
      microdeletions was carried out according to the standard EAA/EMQN guidelines. The
      breakpoints were mapped for the deletions in AZF locus. The Y chromosome macro-
      and microdeletions were detected in 61 (7.5%) infertile men. The frequencies of
      AZF deletions during azoospermia and severe oligozoospermia amounted to 12.2 and
      8.1 %, respectively. On the whole, the frequencies of Yq microdeletions and the
      genophenotypic correlations characteristic of various AZF deletion types comply
      with the relevant published data. However, spermatozoids in the ejaculate
      sediment of men with completely deleted AZFa region or AZFb+c deletions (from
      solitary spermatozoids to several dozens) were detected for the first time. It
      was demonstrated that the breakpoints were localized between AZFa and AZFb
      regions proximally to AZFb+c microdeletions for the majority of cytogenetically
      detectable deletions in the Y chromosome long arm. This indicates that the
      mechanisms underlying Yq macro- and microdeletions are somewhat different. The
      issues related to the role of Y chromosome deletions in the origins of monosomy
      for X chromosome and X/XY mosaicism are discussed.

PMID- 17025165
TI  - [Population analysis and determination of the ethnic background are necessary in
      the study of multifactorial diseases: a study using the Dagestan population as a
      model].
AB  - Psoriasis, a multifactorial disease with genetic predisposition, has been used as
      an example to study the role of the ethnic background in multifactorial diseases
      in the Dagestan population. The individual information card (IIC) is proposed as
      the main tool for correct collection and processing of information. The results
      of the study demonstrate that the Dagestan population is a convenient and
      adequate model population for studying multifactorial diseases, such as
      psoriasis, and may serve as an object for studying the role of heredity in the
      etiologies and pathogeneses of this and other multifactorial diseases.

PMID- 17025166
TI  - [Comparative analysis of N-acetylation polymorphism in humans as determined by
      phenotyping and genotyping].
AB  - The N-acetylation polymorphisms of volunteers from the Moscow population analyzed
      by phenotyping and genotyping have been compared. The ratios between the
      proportions of fast acetylators (FAs) and slow acetylators (SAs) estimated by
      phenotyping and genotyping do not differ significantly from each other (47 and
      44%, respectively). The absolute acetylation rate widely varies in both FAs and
      SAs. The NAT2 genotype and allele frequencies in the population sample have been
      calculated. The most frequent alleles are NAT2*4 (a "fast" allele), NAT2*5, and
      NAT2*6 ("slow" alleles); the most frequent genotypes are NAT2*5/*5, NAT2*4/*6,
      and NAT2*4/*5. Comparative analysis of N-acetylation polymorphism estimated by
      phenotyping and genotyping in the same subjects has shown a complete concordance
      between the phenotype and genotype in only 62 out of 75 subjects (87%).
      Comparative characteristics and presumed applications of the two approaches
      (quantitative estimation of acetylation rate and qualitative determination of the
      acetylator genotype) to the identification of individual acetylation status are
      presented.

PMID- 17025167
TI  - [Population organization and communication in microorganisms].
AB  - This review concentrates on the history of the subfield of microbiology referred
      to as the population organization- and communication-related research direction
      (POCRRD). The focal points of POCRRD include intercellular interactions,
      information exchange between cells, and multicellular structures (colonies,
      biofilms, flocs, etc.). Special attention in this review is given to the
      contribution of Russian scientists to the development of POCRRD. In terms of
      POCRRD, microorganisms are viewed as social creatures that constantly communicate
      and form supraorganismic, intrinsically heterogeneous systems.

PMID- 17025168
TI  - [Adaptive functions of extracellular autoregulators of microorganisms].
AB  - Information about the functions of extracellular autoregulators, which adapt
      microorganisms to the stresses "scheduled" in the development cycle of microbial
      cultures (stresses of new medium, starvation, or space exhaustion (high cell
      density)) is summarized in the review. In a number of bacteria and yeasts,
      derivatives of alkylhydroxybenzenes (AHB), particularly of the class of alkyl
      resorcinols, act as autoregulators with adaptogenic functions. The chemical
      structure of AHB determines their amphiphility; capacity for physical and
      chemical interaction with membrane lipids, proteins, and DNA; properties as
      natural modifiers of biological membranes and enzymes; and the expression of
      antioxidant activity. Increase of AHB concentration up to the critical level (10(
      5)-10(-4) M) results in cessation of cell division and in transition of the
      microbial culture to the stationary phase; further increase to 10(-4)-10(-3) M
      induces a transition of some of the cells of a post-stationary culture to the
      anabiotic state with the formation of cystlike resting cells (CRC), even in non
      spore-forming bacteria. AHB participate in the regulation of the phenotypic
      variability of bacteria. The dynamics of extra- and intracellular concentrations
      of AHB in growing microbial cultures and the polymodality of their effect
      determine the adaptogenic functions of AHB as autoinhibitors of culture growth,
      autoinducers of anabiosis, and autoinhibitors of germination of resting forms.
      Manifestation of any given function depends on the concentration of AHB, the
      physiological state of the recipient cells, and on environmental factors. The
      species nonspecificity of AHB effects points to their significant role in the
      regulation of the development and functioning of microbial communities.

PMID- 17025169
TI  - [Quorum-sensing regulation of gene expression: fundamental and applied aspects
      and the role in bacterial communication].
AB  - Quorum sensing (QS) is a specific type of regulation of gene expression in
      bacteria; it is dependent on the population density. QS systems include two
      obligate components: a low-molecular-weight regulator (autoinducer), readily
      diffusible through the cytoplasmic membrane, and a regulatory receptor protein,
      which interacts with the regulator. As the bacterial population reaches a
      critical level of density, autoinducers accumulate to a necessary threshold value
      and abrupt activation (induction) of certain genes and operons occurs. By means
      of low-molecular-weight regulators, bacteria accomplish communication between
      cells belonging to the same or different species, genera, and even families. QS
      systems have been shown to play a key role in the regulation of various metabolic
      processes in bacteria and to function as global regulators of the expression of
      bacterial genes. Data are presented on different types of QS systems present in
      bacteria of various taxonomic groups, on the species specificity of these
      systems, and on communication of bacteria by means of QS systems. The possibility
      is considered of using QS regulation systems as targets while combating bacterial
      infections; other applied aspects of QS investigation are discussed.

PMID- 17025171
TI  - [A comparative study of the inducing effect of homoserine lactone and
      hexylresorcinol on phenotypic dissociation in bacteria].
AB  - It has been shown that the phenotypic dissociation of Bacillus subtilis SK1 and
      S. typhimurium TA100 is induced by hexylresorcinol, an exogenous non-species
      specific autoregulator of pleiotropic action, which is genotoxic for both pro-
      and eukaryotes. Nongenotoxic homoserine lactone, a chemical analogue of cell
      density-responsive species-specific regulators, does not induce bacterial
      dissociation. The phage resistance of the S- and R-type variants of S.
      typhimurium TA100 induced by hexylresorcinol has been found to be the same as
      that of the S- and R-type salmonella variants obtained by the routine
      subculturing method.

PMID- 17025170
TI  - [Quorum-sensing regulation in soil pseudomonads].
AB  - 228 strains of soil and rhizosphere pseudomonads isolated in different geographic
      zones were screened, with the use of two tester systems, for the capacity to
      produce N-acetyl-homoserine lactones (AHLs), which are autoinducers involved in
      quorum-sensing (QS) regulation. AHL production was found in 11.4% of the strains
      investigated. In five Pseudomonas chlororaphis strains shown to be active AHL
      producers and chosen for further study, PCR identified two QS systems that
      involved the phzI, phzR, csaI, and csaR genes; this finding suggests the
      conservative nature of these regulation systems in P. chlororaphis. Strain P.
      chlororaphis 449, chosen as a model object and studied in greater detail,
      produced three AHL species including N-butanoyl-homoserine lactone and N-hexanoyl
      homoserine lactone. This strain produced three types of phenazine antibiotics, as
      well as siderophores and cyanide; it also exhibited antagonistic properties
      toward a wide spectrum of phytopathogenic fungi. The phzI and csaI genes, coding
      for synthases of AHLs of two types, were cloned and sequenced; mutants with
      knocked-out phzI and csal genes were obtained. With the use of transposon
      mutagenesis and the gene substitution method, mutations were obtained in the
      global expression regulator genes gacS, coding for the GacA-GacS regulation
      system kinase, and rpoS, coding for the sigma S subunit of RNA polymerase. The
      effect of these mutations on the AHL synthesis and on the regulation of various
      metabolic processes in P. chlororaphis was studied.

PMID- 17025172
TI  - [Non-species-specific effects of unacylated homoserine lactone and
      hexylresorcinol, low molecular weight autoregulators, on the growth and
      development of bacteria].
AB  - We conducted a comparative study of the effects of alpha-amino-gamma
      butyrolactone, the common structural element of extracellular microbial
      regulators of the homoserine lactone (HSL) group, and of 4-n-hexylresorcinol, an
      autoregulator of the alkylhydroxybenzene (AHB) group, on the growth and
      development of gram-positive and gram-negative bacteria. We revealed non-species
      specific effects of HSL and AHB and characterized their concentration
      dependencies. The addition of 10(-5)-10(-3) M HSL or 10(-5)-10(-4) M AHB during
      the exponential growth phase of the cultures grown on balanced media resulted in
      cell division arrest and accelerated the transition to the stationary phase that
      culminated in endospore formation in Bacillus cereus, Alicyclobacillus tolerans,
      and Sulfobacillus thermosulfidooxidans. When bacilli grew under the cultivation
      conditions that resulted in a low-zero spore percentage, 10(-4)-10(-3) M HSL
      cancelled the inhibition of spore formation. In the gram-negative bacteria
      Pseudomonas aurantiaca and Azotobacter vinelandii, AHB at concentrations of 10(
      4) to (1.5-2.5) 10(-4) M induced the formation of dormant cells. Studies with the
      actinobacterium Streptomyces avermitilis revealed that the HSL effect varied
      depending on the age of the test cultures. The addition of 10(-4) M HSL during
      the lag phase of a submerged streptomycete culture accelerated its transition to
      the stationary phase and induced the formation of endospores, the dormant cells
      that are regarded as alternatives to exospores (conidia). If HSL (3.64 and 4.55
      mg per 1cm2 disc) was locally added to a surface S. avermitilis culture, the
      growing mycelium formed rings that differed in their density, in the extent of
      the development of aerial mycelium, and in the presence/absence of exospores.
      Ring-shaped growth of streptomycete mycelia was also induced by 0.075-0.75 mg of
      AHB; however, unlike HSL, AHB repressed exospore formation. The data on non
      species-specific effects of HSL and AHB suggest that they may perform regulatory
      functions on the microbial community level.

PMID- 17025173
TI  - [Regulatory functions of bacterial exometabolites].
AB  - This review deals with the issue of growth autoregulation and survival in
      bacterial cultures under starvation conditions. Based on our results and on
      published data, the conclusion has been drawn that low-molecular products of
      metabolism (carboxylic acids, amino acids, and other metabolites) perform
      regulatory functions. The same compounds also control the ecological relationship
      between microorganisms at the interspecific level, and affect their antagonistic
      activity. It is suggested that complexes of bacterial metabolites can be used for
      controlling the composition of various microbiocenosis, including those of
      humans.

PMID- 17025174
TI  - [Autoregulation of stress response in microorganisms].
AB  - Examples are considered of the involvement of low-molecular-weight autoregulators
      in the development of resistance of proliferating microbial cultures to
      unfavorable environmental impacts of various intensity, including impacts
      programmed to occur in the developmental cycle ("new medium stress," starvation
      stress) and nonprogrammed impacts. It was shown that extracellular adaptation
      factors control the reversible adhesion of cells in submerged cultures and the
      processes of cell reactivation in the poststress period and are involved in the
      stabilization of cellular biopolymers (proteins and DNA) and subcellular
      structures (membranes); the adaptogens of the phenolic type also act as efficient
      scavengers of reactive oxygen species. The protective effect of the adaptogenic
      autoregulators is manifested in the increase of resistance of microbial cells to
      stressors of various nature and in the preservation of the cell proliferative
      capacity.

PMID- 17025175
TI  - [Oxidative stress and cell differentiation in Neurospora crassa].
AB  - Environmental stress factors induce oxidative stress in fungi by increasing the
      intracellular concentrations of reactive oxygen species (ROS). In the mycelium,
      ROS act as signal molecules needed for cytodifferentiation at certain stages of
      the development of fungi. Generation of ROS in cells induces the activation of
      antioxidant protective mechanisms. The purpose of this communication is to
      analyze the role of ROS in light signal transduction, mediated in Neurospora
      crassa cells by the White Collar Complex.

PMID- 17025176
TI  - [Cell-cell interactions during formation and reactivation of "nonculturable"
      mycobacteria].
AB  - To date, the possible existence of "nonculturable" (NC) but potentially viable
      forms has been shown for some bacteria. NC mycobacteria have attracted particular
      interest due to the assumption that the latent form of tuberculosis is associated
      with the conversion of its causative agent, Mycobacterium tuberculosis, into the
      NC state. A number of approaches have been developed to obtain NC forms of
      mycobacteria, but the mechanisms of transition into or from this state have been
      insufficiently studied. This review considers cell-cell communications involved
      in the formation and reactivation of NC forms of the bacteria M. smegmatis and M.
      tuberculosis. Special attention has been paid to the secreted Rpf family
      proteins, which belong to peptidoglycan hydrolases and participate in the
      resuscitation of NC mycobacteria.

PMID- 17025177
TI  - [Export of metabolites by the proteins of the DMT and RhtB families and its
      possible role in intercellular communication].
AB  - The earlier published and new experimental data are summarized on the properties
      of the genes encoding the membrane proteins of the DMT family (RhtA (YbiF), EamA
      (YdeD), YijE, YddG, YedA, PecM, eukaryotic nucleoside phosphate sugar and hexose
      phosphate transporters), the RhtB/LysE family (RhtB, RhtC, LeuE, YahN, EamB
      (YfiK), ArgO (YggA), CmaU), as well as some other families (YicM, YdhC, YdeAB,
      YdhE (NorE)). These proteins are involved in the export of amino acids, purines,
      and other metabolites from the cell. The expression of most of the genes encoding
      these proteins is not induced by the substrates they transport but is controlled
      by the global regulation systems, such as the Lrp protein, and activated by the
      signal compounds involved in the intracellular communication. The level of
      expression, assessed in experiments on translational fusion of the corresponding
      bacterial genes with the beta-galactosidase gene, depends on the growth phase of
      the bacterial culture, composition of the medium, and some stress factors, such
      as pH osmolarity or decreased aeration. The efflux of normal cell metabolites is
      assumed to be the natural function of these proteins. This function may play a
      role in density-dependent behavior of cell populations (quorum sensing). It may
      have been enhanced in the course of evolution via specialization of these
      proteins in the efflux of compounds derived from metabolic intermediates and
      adjusted to the role of transmitters.

PMID- 17025178
TI  - [The effect of extracellular metabolites on the frequency of Thy+ revertants in
      Salmonella typhimurium populations].
AB  - There is convincing evidence that adaptation and survival processes in bacterial
      populations depend on cell-to-cell interactions. Our studies showed that the
      frequency of stress-induced His+ reversions in an amino-acid-starved Salmonella
      typhimurium culture is inversely proportional to cell density in this culture.
      The effects of cell density and of different culture liquids prepared from
      cultures varying in physiological age on the frequency of Thy+ revertants were
      also studied. It was found that the frequency of Thy+ revertants is inversely
      proportional (r = -0.74) to the density of the bacterial culture starved of
      thymine. The culture liquid prepared from the culture starved of histidine
      exerted an inhibitory effect on the frequency of Thy+ reversions, indicating that
      mutations induced by different types of stress have a common mechanism. The study
      of the effect of the culture liquid prepared from a histidine-starved culture on
      the frequency of ethyl- methanesulfonate-induced His+ revertants showed that this
      liquid prevented the induction of His+ reversions.

PMID- 17025180
TI  - [Behavior of filamentous cyanobacteria in laboratory culture].
AB  - The observations of a laboratory culture of filamentous cyanobacteria revealed a
      complex of behavioral responses of their community, which maintain their activity
      as an integrated entity. A number of structures formed in the course of filament
      regrouping were revealed and described; their possible structural and functional
      analogues in eukaryotic organisms were determined. It is assumed that the
      behavioral reactions of the filaments help to maintain the integrity of the
      community at the stage prior to the formation of the structural bonds between its
      elements.

PMID- 17025179
TI  - [Host factors in the regulation of the Vibrio fischeri lux operon in Escherichia
      coli cells].
AB  - It has been shown that the chaperonin GroEL, together with GroES co-chaperonin
      and Lon ATP-dependent protease are involved in the regulation of expression of
      the Vibrio fischeri lux operon in Escherichia coli cells. The cells of E. coli
      groE (pF1)- bearing a plasmid with the complete V. fischeri lux regulon were
      weakly luminescent. The cells of E. coli lonA (pF1) displayed intense
      bioluminescence. The same effects also occurred in mutant E. coli strains bearing
      a hybrid plasmid pVFR1, where the luxR gene and the regulatory region of the V.
      fischeri lux operon were inserted before the Photorhabdus luminescens luxCDABE
      cassette. The V. fischeri luxR gene was cloned in the pGEX-KG vector with the
      formation of a hybrid gene gst-luxR. It was shown that affinity chromatography of
      the product of expression, the chimeric protein GST-LuxR, on a column with
      glutathione-agarose resulted in its copurification with the proteins GroEL and
      Lon. Consequently, LuxR, the transcription activator of the lux operon, forms
      complexes with these proteins. It is supposed that GroEL/GroES is responsible for
      the folding of the LuxR protein, and Lon protease degrades the LuxR protein
      either before its folding into an active globule or at denaturing.

PMID- 17025181
TI  - [Communication of cyanobacteria with plant partners during association
      formation].
AB  - Data are presented on the physiological diagnostics of cyanobacterial
      communication with higher plants in natural symbioses (plant syncyanoses) and in
      model associations, as well as on the interaction of the partners without spatial
      integration. Emphasis is placed on changes in cyanobacterial features important
      for symbiogenesis. The multicomponent structure and the possible nature of the
      factors that enable partner communications are discussed with hormogonia
      formation and taxis as an example.

PMID- 17025182
TI  - [Wheat lectin as a factor in plant-microbial communication and a stress response
      protein].
AB  - Wheat lectin (wheat germ agglutinin, WGA), a representative of a broad group of
      cereal lectins, is excreted by plant roots into the surrounding medium and
      interacts with both pathogenic microflora and growth-stimulating rhizobacteria.
      WGA was found to serve as a molecular signal for the rhizobacterium Azospirillum
      brasilense, which forms endophytic and associative symbioses with wheat plants.
      The bacterial response to the lectin was pleiotropic: WGA at concentrations from
      10(-10) to 10(-6) M exerted a dose-dependent effect on a range of processes in
      the bacterium that are important for the establishment and functioning of
      symbiosis. Plants with different WGA content differed in their responses to
      severe nitrogen starvation and to seed treatment with Azospirillum.

PMID- 17025183
TI  - [The electron microscopic study of cell-to-cell interactions between antagonistic
      microorganisms].
AB  - The electron microscopic study of thin sections and positively stained specimens
      of cells taken from particular cocultures of Lactobacillus acidophilus D75,
      Lactobacillus casei YIT 9018, Shigella flexnery 2a, Bacillus subtilis ATCC 6633,
      and Staphylococcus aureus ATCC 25923 (some of these bacteria are antagonistic to
      others) showed the presence of specific ultrastructural elements indicating cell
      specialization and cooperation. The responses of antagonistic bacteria manifested
      themselves at the cellular and population levels.

PMID- 17025184
TI  - [Formation of biofilms as an example of the social behavior of bacteria].
AB  - This paper is a brief review of data on bacterial biofilms that occur inside and
      outside of host organisms. Such biofilms are of great ecological and clinical
      importance. The role of interspecies communications in the development of
      bacterial biofilms and infectious diseases is particularly emphasized.
      Considerable attention is given to the electron microscopic study of biofilms
      formed by Salmonella typhimurium cells incubated as a broth culture in microtubes
      without aeration. Bacterial samples taken from the biofilm and planktonic culture
      grown in the same microtube were comparatively investigated by transmission
      electron microscopy.

PMID- 17025185
TI  - ["Oxygen regulation" of the respiratory chain composition in the yeast
      Debaryomyces hansenii under multiple stress].
AB  - It was shown that two stress factors, hypoxia and hyperosmotic shock, if applied
      simultaneously to the yeast Debaryomyces hansenii, display an antagonistic mode
      of interaction, which results in an increased degree of halophily of this
      microorganism under microaerobic conditions. Studies of the effects of
      respiration inhibitors (sodium azide and salicyl hydroxamic acid, SHA) and of the
      pattern of changes in the composition of the respiratory chain of Debaryomyces
      hansenii under the stated stress conditions led to the suggestion of three (or
      four) chains of electron transfer functioning simultaneously in the cell: the
      classical respiratory chain involving cytochrome-c oxidase, an alternative
      respiratory chain involving a cyanide- and azide-resistant oxidase, and
      additional respiratory chains involving oxidases resistant to salt, azide and
      SHA. Thus, the antagonistic mode of interaction between hypoxia and hyperosmotic
      shock results from the redirection of the electron flow from the salt-susceptible
      respiratory systems to the salt-unsusceptible ones encoded by "the hypoxia genes"
      and activated (induced) under microaerobic conditions.

PMID- 17025186
TI  - [Production of vitamin B12 in aerobic methylotrophic bacteria].

PMID- 17025187
TI  - [Spatial organization of biopotentials and original features of visual images].
AB  - Features of spatial organization of neocortical potentials during mental creating
      of the original and standard visual images were studied. Intrahemispheric and
      interhemispheric coherence in different EEG frequency bands and temporal
      relations between relative changes in the index of linear (correlation
      coefficient) and non-linear (multiple entropy) processes in different neocortical
      areas were analysed. Number of decreased coherence values in the high-frequency
      alpha subband between remote neocortical points during creating of an original
      image was significantly lower than during creating of a standard image. During
      creating of the original image, the number of synchronously functioning pairs of
      neocortical areas and the mean level of linear correlation between the areas were
      higher, and correlation by the non-linear index, on the contrary, was lower than
      during creation of the standard image. The correlation between changes in
      different neocortical areas for both processes during creating of the original
      image was only positive, and that during creating of the standard image was both
      positive and negative. The conclusion was made that creative and reproductive
      types of visual imagination were different in the spatial distribution of
      coordinated changes in the linear and non-linear processes, mean magnitudes of
      these changes, and the character of hemispheric interaction. The data on
      different interhemispheric relations in diagonal and central bilateral directions
      raise a question about the radial representation of visual imagination.

PMID- 17025188
TI  - [Specific features of lateralization of a stationary auditory image by a human
      under condition of stimulation without interaural differences: a
      neurophysiological analysis].
AB  - Analysis of the lateralization phenomena of a fused auditory image (FAI) was
      performed on the basis of the previously developed model of the binaural
      directional hearing. It was found earlier that, under conditions of auditory
      stimulation without interaural differences, the FAI was localized at the head
      midline only in about a quarter of subjects. In a greater part of the listeners,
      the FAI was lateralized within the range of -4.6 ... +11.2 degrees from the
      midline. It was shown that FAI localization with reference to the head midline
      may be determined by the extent of asymmetry and spatial contrast between the
      "active" neural zones in the left and right halves of the subjective auditory
      space. In turn, the asymmetry (or its absence) of these "active" zones fully
      depends on a distribution of neurons by characteristic time delays in the left
      and right halves of the subjective auditory field. The model also explains the
      fact of a decrease in localization precision with the FAI position just at the
      midline.

PMID- 17025189
TI  - [Dopamine system genes and personality traits of extraversion and novelty
      seeking].
AB  - Dopamine neurotransmissin is thought to play a relevant role in behavioral
      reinforcement system. Polymorphism of the genes involved in dopamine system has
      been reported for association with psychological traits related to impulsive and
      sensation seeking behaviors. The study was aimed at a search for association of
      catechol-O-metyltransferase (COMT) and dopamine receptor D4 (DRD4) gene
      polymorphism with personality traits in Russian population. A sample comprised
      130 subjects. It was found that carriers of the Met/Met COMT genotype had higher
      scores of novelty seeking as compared to those with the Val/Val and Met/Met
      genotypes. The association was observed in women only. In the presence of the C
      allele of the DRD4 gene, females with the Met/Met genotype demonstrated higher
      scores on extraversion and hypomania. The results are consistent with the current
      theoretical concepts on the regulation of dopamine neurotransmission in the
      brain.

PMID- 17025190
TI  - [Gender-related differences in EEG coherence in Stroop task].
AB  - Gender-related differences in EEE coherence were studied in young male and female
      university students during performance of Stroop task, in which color and word
      could be congruent or incongruent and spatially integrated or separated. The most
      clear-cut gender-related differences in the EEG coherence were revealed in the
      alpha2 and beta frequency bands. In the alpha2 band, gender-related differences
      in the interhemispheric coherence were associated with spatial characteristics of
      stimuli: left or right presentation and features of mutual localization of
      relevant and irrelevant stimuli. These differences were observed when information
      was addressed to the left hemisphere. Gender-related differences associated with
      spatial organization of stimuli were also observed for intrahemispheric beta1
      coherence. Under conditions of the spatial separation of relevant and irrelevant
      stimuli, only females demonstrated enhancement of coherence in response to the
      right-side stimulus presentation as compared to the left-side presentation. It
      was shown that, during the differentiation of the semantic meaning of verbal
      stimuli, gender-related differences were caused by the features of integration of
      beta2 oscillators in the posterior cortical regions. The results are indicative
      of qualitative gender-related differences in organization of both frontoparietal
      and lateral attention systems in actualization of selective processes.

PMID- 17025191
TI  - [Spatial synchronization of cortical electrical activity at different stages of
      visual set in preschool children].
AB  - Changes in the alpha-rhythm synchronization were revealed at different stages of
      cognitive visual set in 5- to 7-year-old children. We found a clear-cut
      correlation of these changes with set plasticity. In children with a plastic set,
      the EEG synchronization between the frontal and other brain regions substantially
      increased in the period of set-shifting (the actualization stage). At the set
      extinction stage, after set-shifting has already taken place, the EEG
      synchronization becomes minimal. On the contrary, in children who formed a rigid
      set, EEG coherence considerably increases at the set extinction stage. This
      finding suggests that the rigid set still affects the cognitive activity even
      after (judging from oral reports) the set shift has been completed. The age
      related differences in cognitive set formation clearly correlate with the time
      course of the EEG synchronization between the frontal and other brain regions. We
      think that the ability to form a plastic visual set depends on the frontal cortex
      maturation, which occurs at the age of 6-7 years, and its age-related effect on
      the brain cognitive functions.

PMID- 17025192
TI  - [Personality-related differences in recognition of facial emotional expression
      and cortical evoked potentials].
AB  - A correlation between some characteristics of the visual evoked potentials and
      individual personality traits (by the Kettell scale) was revealed in 40 healthy
      subjects when they recognized facial expressions of anger and fear. As compared
      to emotionally stable subjects, emotionally unstable subjects had shorter
      latencies of evoked potentials and suppressed late negativity in the occipital
      and temporal areas. In contrast, amplitude of these waves in the frontal areas
      was increased. In emotionally stable group of subjects differences in the evoked
      potentials related to emotional expressions were evident throughout the whole
      signal processing beginning from the early sensory stage (P1 wave). In
      emotionally unstable group differences in the evoked potentials related to
      recognized emotional expressions developed later. Sensitivity of the evoked
      potentials to emotional salience of faces was also more pronounced in the
      emotionally stable group. The involvement of the frontal cortex, amygdala, and
      the anterior cingulate cortex in the development of individual features of
      recognition of facial expressions of anger and fear is discussed.

PMID- 17025193
TI  - [Neonatal buspirone modulates the intermale aggression in adult mice].
AB  - Mice of two strains with different levels of male aggression (RSB and RLB) were
      subjected to daily injections of 5-HT1A receptor agonist buspirone (25 microg) on
      the 2nd - 6th postnatal days. This neonatal treatment augmented the aggressive
      behavior (tested in the dyadic contests with non-aggressive A/Sn males) in
      aggressive RSB mice and reduced aggression in less aggressive RLB. Correlations
      with different signs were found between the 5-HT and 5-HIAA levels in the
      neocortex, hippocampus, and hypothalamus and behavioral indices of aggression in
      RSB and RLB males. The remote effects of neonatal buspirone in these two mice
      strains presumably depend on genotype-related features of ontogeny of the 5-HT
      system.

PMID- 17025194
TI  - [Effect of zif268 early gene antisense oligonucleotide on mechanisms of synapse
      specific plasticity].
AB  - It was found that nociceptive sensitization was followed by long-term
      facilitation of synaptic responses evoked by chemical sensory stimulation of the
      snail "head", tactile stimulation of the snail "head" and foot in LP11 command
      neuron of defence behavior in snail Helix lucorum. Sensitizing stimulation during
      the intracellular injection of antisense olygonucleotide immediate early gene
      zif268 resulted in a selective suppression of synaptic facilitation in LP11
      neuron responses evoked by tactile and chemical stimulation of the snail "head".
      At the same time, development of synaptic facilitation of responses in the LP11
      neuron evoked by tactile stimulation of the foot was the same as in control
      sensitized snails. The results suggest that immediate early gene zif268 is
      selectively involved in the mechanisms of specific regulation of plasticity of
      the synaptic "input" of LP11 neuron from sensory receptors of the snail "head".

PMID- 17025195
TI  - [Neurophysiological and simulation study of the striate receptive fields maps:
      the role of intracortical interaction].
AB  - In 27 acute experiments with anesthetized and immobilized adult cats 101 maps of
      receptive field (RF) in 67 striate neurons were studied by means of mapping with
      single flashed stimuli presented in different parts of the visual field and under
      conditions of additional activation of the RF excitatory center by the local
      oscillating or flashing grid. Under conditions of both classical and combined
      modes of mapping, the RFs of the classical shape with a single excitatory zone
      (63.4 and 29.3% of cases, respectively) and RFs with multiple (2-5) excitatory
      and/or inhibitory zones (36.6 and 70.7%, respectively) were found. We were the
      first to describe, also, some RFs of horseshoe-like, cross-like and T-like
      shapes. Simulation of non-classical RFs revealed possible contributions of
      cooperative excitatory and inhibitory intracortical interactions to the effects
      under study. The functional role of RFs of different types in the feature
      detection is discussed.

PMID- 17025196
TI  - [The area of the optically activated zones of cat area 17 under stimulation with
      grids of different orientation].
AB  - In acute experiments with 9 anesthetized and immobilized cats, the relative
      tangential square of the activated cortical columns in area 17 was mapped by the
      intrinsic optical signal under stimulation with grids of different orientation.
      We examined the "oblique effect", i.e. the greater representation of neurons
      tuned to the vertical and horizontal orientations vs. oblique orientations in the
      primary visual cortex. The square of the activated parts of the cortex was
      estimated under different threshold criteria (80, 60 and 40% of the maximum). The
      "oblique effect" was not observed in our study: the areas of activation of the
      cortical columns did not differ statistically for two basic vs. oblique
      orientations. Reasons for the difference between the results of
      electrophysiological and optical mapping are suggested and possible contributions
      of the experimental protocol (anesthesia) and individual visual experience in
      different animals' samples to the origin of these differences are discussed.

PMID- 17025197
TI  - [Effects of fluoxetine on locomotor activity: possible involvement of dopamine].
AB  - Plus-maze benavior of adult mail rats was assessed and contents of 5
      hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) in different brain regions
      were analyzed after two-week fluoxetine treatment (25 mg/kg/day, per os). Chronic
      fluoxetine treatment produced a general decrease in the brain 5-HIAA content and
      a decrease in DA content in the frontal cortex and striatum. Behaviorally,
      fluoxetine-treated animals displayed enhanced anxiety and decreased locomotor
      activity. The DA depletion os supposed to be responsible for fluoxetine-produced
      hypolocomotion. This is supported by a significant correlation between the
      dopamine content in the frontal cortex and the number of entries into the closed
      arms of the plus-maze. The results suggest that the hypolocomotor effect of
      fluoxetine may involve the changes in the dopaminergic system.

PMID- 17025198
TI  - [Correlation between the levels of calcium in the blood and catecholamines in the
      brain during memory formation and fixation in hypoparathyreosis].
AB  - Relationship between the blood level of calcium and the level of catecholamines
      in the brain limbic structures was studied in passive avoidance conditioning and
      extinction in rats with hypoparathyreosis. After parathyroidectomy, conditioning
      processes were shown to be impaired as a result of a disorder of calcium supply.
      In hypoparathyreosis, not only the basic dopamine and noradrenalin levels change,
      but catecholamine dynamics in learning and forced extinction of a passive
      avoidance reaction shifts. The results point to the deranged functioning of
      dopamine and noradrenaline brain systems as a result of disorders in calcium
      homeostasis. These shifts result in disorders of conditioning and development of
      an adaptive behavioral strategy.

PMID- 17025199
TI  - [The involvement of brain 5-HT(1A)-receptors in genetically determined aggressive
      behavior].
AB  - The hypothesis was tested that one of the critical mechanisms underlying
      genetically determined aggressiveness involves brain serotonin 5-HT(1A)
      receptors. The expression of 5-HT(1A)-receptor mRNA in brain structures and
      functional correlate for 5-HT(1A)-receptors identified as 8-OH-DPAT-induced
      hypothermia were studied in Norway rats bred over the course of 59 generations
      for the low and high affective (defensive) aggressiveness with respect to man and
      in highly aggressive (offensive) MAO A-knockout mice (Tg8 strain). Considerable
      differences between the aggressive and the nonaggressive animals were shown.
      Agonist of 5-HT(1A)-receptor 8-OH-DPAT (0.5 mg/kg for rats and 2.0 mg/kg for
      mice, i.p.) produced a distinct hypothermic reaction in nonaggressive rats and
      mice and did not affect significantly the body temperature in aggressive animals.
      In aggressive rats, a significant reduction of the expression of 5-HT(1A)
      receptor mRNA was found in the midbrain. In Tg8 mice, 5-HT(1A)-receptor mRNA
      level was increased in the frontal cortex and amygdala and not changed in the
      hypothalamus and the midbrain. The results provide support for the idea that
      brain 5-HT(1A)-receptors contribute to the genetically determined individual
      differences in aggressiveness.

PMID- 17025200
TI  - [Alteration of active and passive Wistar rats adaptive behavior in water
      immersion model of depression].
AB  - Animals with active and passive behavioral strategy were selected among male
      Wistar rats by testing them in the T-maze. Using the results of rats testing in T
      maze index of behavioral activity and index of behavioral passivity were
      calculated. The development of post-stress psychopathology and ils correlation
      with initial behavioral strategy were studied under water-immersion stress
      conditions consiclering individual alteration of adaptive behavior. Two paradigms
      were used--one time trial (stress) and two times trial (stress-restress). It was
      found that active and passive rats being subjected to inescapable aversive
      exposure develop different types of post-stress depression and only passive
      animals show the signs of posttraumatic stress disorder.

PMID- 17025201
TI  - [The effects of neonatal saline injections on behaviours in DBA/2 male mice].
AB  - DBA/2 male mice were exposed to the injections of the saline (0.01 ml/g i.p.) on
      1-th, 3-th, 5-th, 7-th, 9-th days after birth. Intact males were used as a
      control group. Adult saline-treated males displayed the increased number of
      crossed squares, entries in the centre and time spent in the centre during the
      open "field" test in comparison with intact animals. The time spent in the light
      compartment of the light-dark box was decreased in saline treated mice compared
      with intact animals. During the test of acoustic startle response the magnitude
      of startle reflex and prepulse inhibition didn't change the startle reflex.
      Saline administration in males did not affect corticosterone basal level. Sexual
      motivation was revealed to decrease in saline treated males. These data suggest
      that neonatal administration of saline induced a stable behavioral syndrome in
      adult DBA/2 male mice: hyperactivity, a decrease of open space fear and
      simultaneously an increase of some indices of anxiety.

PMID- 17025202
TI  - [Memory and depressions].
AB  - A hypothesis of depression development is put forward. It is suggested that
      depression develops as a result of the disorders of the normal mechanisms of
      learning and memory. To assess the hypothesis, a functional system of behavioral
      control with the key role of memory apparatus and its links with other units of
      the system is proposed. According to the behavioral control system, memory is
      organized and works as the integration of activity of sensory, motivational and
      emotional inputs. It was shown that disorders of each of these inputs make
      specific contribution into the origin and manifestations of depression and
      corresponding morphological, electrophysiological, trophic, neurochemical,
      molecular-genetic and other changes.

PMID- 17025203
TI  - [Colorectal carcinoma].

PMID- 17025204
TI  - [Diabetes mellitus].

PMID- 17025205
TI  - [Acute bronchitis and influenza].

PMID- 17025206
TI  - [Spondylarthropathies].

PMID- 17025207
TI  - [Primary glomerulonephritis].

PMID- 17025208
TI  - [Clinical experience on 52 patients with interstitial cystitis].
AB  - PURPOSE: To examine clinical features of the patients of interstitial cystitis
      (IC) undergoing hydrodistension at our institution. MATERIALS AND METHODS: We
      retrospectively evaluated 52 IC patients who underwent hydrodistension between
      July 2002 and December 2004. Transurethral coagulation (TUC) of Hunner's ulcer
      (HU) was subsequently performed for patients with HU (ulcer type). Descriptive
      statistics of the patients' characteristics and outcomes were provided and
      compared between ulcer type and nonulcer type IC patients. RESULTS: Of the 52
      patients, 44 (85%) were female and 8 were male. Mean symptom duration at
      diagnosis was 59 months (range 2 to 388). Mean patient age was 55 years (range 24
      to 78). Of them, 92% reported urinary frequency, 54% bladder or lower abdominal
      pain and 40% voiding difficulty. The daily voiding frequency was 19 times (range
      8 to 52) and mean bladder capacity by voiding log was 100 ml (range 33 to 260).
      The mean of bladder capacity at hydrodistension was 580 ml (range 220 to 880).
      All the patients showed glomerulations during hydrodistension and 75% of them
      experienced amelioration of their symptoms after hydrodistension. Symptom relief
      lasted for 1 year for two thirds of the patients. Mean observation period was 15
      months (range 2 to 30 months). Of 52 patients, 19 (37%) were ulcer type, who were
      significantly older at diagnosis (60 yrs vs. 52 yrs), had smaller maximum bladder
      capacity of voiding log (140 ml vs. 230 ml) and bladder capacity at
      hydrodistension (500 ml vs. 620 ml). However, ulcer type IC patients responded
      significantly better to hydrodistension (95%vs. 64%). CONCLUSIONS: IC patients
      suffered from severe symptoms for a long time without correct diagnosis or proper
      treatments. Hydrodistension was effective for IC patients, especially for ulcer
      type, combined with TUC.

PMID- 17025209
TI  - [Gemcitabine and cisplatin therapy in advanced or metastatic urothelial cancer:
      comparison of side effect with MVAC (methotrexate, vinblastine, doxorubicin, and
      cisplatin)].
AB  - OBJECTIVE: Cisplatin-based combination chemotherapy has been considered as
      standard therapy for advanced or metastatic urothelial carcinoma. A recent study
      has, however, revealed that gemcitabine may have the potential to act
      synergistically with cisplatin. Therefore, the side effects of gemcitabine plus
      cisplatin (GC) therapy were compared with those of methotrexate, vinblastine,
      doxorubicin and cisplatin (MVAC) therapy in patients with advanced or metastatic
      urothelial carcinoma. PATIENTS AND METHODS: Twenty-two patients received GC
      therapy. Gemcitabine (1000 mg/m2) was administered on days 1, 8 and 15 of each 28
      day cycle. Cisplatin (70 mg/m2) was administered on day 2 of each cycle. As a
      control group, 24 patients received MVAC therapy (methotrexate at 30 mg/m2 on
      days 1, 15, 22, vinblastine at 3 mg/m2 on days 2, 15, 22, doxorubicin at 30 mg/m2
      on day 2, and cisplatin at 70 mg/m2 on day 2 of each 28-day cycle. RESULTS: In
      the group of patients which received GC therapy, the overall response rates based
      on independent radiologic reviews of the 20 patients with measurable disease were
      55%, with 20% CR and 35% PR. Fewer GC patients as compared with MVAC patients had
      grade 3/4 anorexia (4.5% vs. 75%, respectively), stomatitis (9.0% vs. 66.7%,
      respectively), and alopecia (27.3% vs. 100%, respectively). On the other hand,
      there were no significant differences in the incidence or pattern of hematologic
      toxicities between the group receiving GC therapy and that receiving MVAC
      therapy. Fatal neutropenic sepsis occurred in one patient receiving MVAC therapy.
      CONCLUSION: GC therapy is effective for the treatment of advanced or metastatic
      urothelial carcinoma, with an acceptable clinical safety profile. This study also
      indicates that GC therapy may be better tolerated and safer than MVAC therapy.

PMID- 17025210
TI  - [Transrectal biopsy of the prostate for the detection of non-palpable prostate
      cancer: a comparison of 6 versus 12 core biopsy].
AB  - PURPOSE: Several studies suggest that extended transrectal prostate biopsy more
      than 6 core may improve the cancer detection rate. We compared 6 and 12 core
      biopsies to determine the impact on cancer detection and complication rate.
      PATIENTS AND METHODS: We retrospectively evaluated 150 patients who underwent
      transrectal ultrasound guided prostate biopsy between January 1999 and December
      2003. Patients who were suspected to have prostate cancer on digital rectal
      examination and/or who had a history of previous prostate biopsy were excluded.
      Sextant biopsy was performed in 52 patients (6 core group) and 12 core biopsy was
      performed in 98 patients (12 core group). The cancer detection rate and post
      biopsy complication rate were estimated. RESULTS: There was no significant
      difference in the overall cancer detection rate between 6 and 12 core groups (17
      of 52 men or 32.7% versus 35 of 98 men or 35.7%). In addition, even if calculated
      the cancer detection rate stratified according to a PSA of 0 to 4.0, 4.1 to 10.0
      and greater than 10.0 ng/ml, there was no significant difference between both
      groups. There was also insignificant difference of complication rate between both
      groups. CONCLUSIONS: The results of our study showed that there was no
      significant difference in cancer detection and complication rate between both
      groups.

PMID- 17025211
TI  - [Pathological prognostic factors of renal pelvic and ureteral cancer].
AB  - OBJECTIVE: To determine the pathologic risk factors after nephroureterectomy in
      patients with urothelial carcinoma of the renal pelvis and ureter. PATIENTS AND
      METHODS: We investigated the clinicopathological features of 131 patients (94
      males and 37 females) with urothelial carcinoma of the renal pelvis and ureter
      who underwent nephroureterectomy at our department and related facilities from
      August, 1994 to August, 1997. The mean age of the patients was 68 years, ranging
      from 24 to 86 years. RESULTS: The 1-, 3- and 5-year cause-specific survival rates
      (Kaplan-Meier's method) for all of the patients were 91.8%, 76.7%, and 67.8%,
      respectively. The significant prognostic factors for survival rates by univariate
      analysis using the log rank test were tumor stage, infiltration pattern,
      lymphatic invasion, vessel invasion and lymph node metastasis. On the other hand,
      multivariate analysis using Cox proportional hazards regression model showed the
      most influential prognostic factors to be vessel invasion and tumor stage.
      CONCLUSIONS: From these results, in urothelial carcinoma of the renal pelvis and
      ureter underwent nephroureterectomy, we suggested that vessel invasion and tumor
      stage were the independent prognostic factors.

PMID- 17025212
TI  - [Mass screening for prostate cancer in Ikeda City Osaka].
AB  - PURPOSE: Screening with prostate specific antigen (PSA) to detect prostate cancer
      was started in Ikeda City Osaka from 2003 as part of the city's health program.
      We evaluated the first year's result. MATERIAL AND METHOD: Fifty-year-old or
      elder men living in Ikeda City who wanted to have their serum PSA level (Tandem
      R) measured to screen for prostate cancer was entered into the screening program.
      Men whose PSA levels detected to exceed 4.1 ng/ml were told they should visit a
      urologist for further examinations to detect possible prostate cancer. These
      examinations included prostate biopsy. The results of further examinations were
      reported to Ikeda City and evaluated. RESULTS: The population of fifty-years-old
      or elder men in Ikeda City was 18,161. 3738 (21.0%) men had their serum PSA
      levels measured. 367 (9.81%) of the men were told they should undergo further
      examinations to detect possible prostate cancer. 263 (71.7%) men visited a
      urologist for further examinations, and prostate biopsy was performed in 138
      (52.5%) of them. Among these 138, prostate cancer diagnosed in 91 (65.9%). The
      positive rate of prostate biopsy was 65.9% (91/138), The detection rate for
      prostate cancer was therefore 2.43% (91/3738). Patient's numbers for each
      clinical stage were 57 (62.6%) in B, 30 (32.9%) in C, 4 (4.4%) in D. CONCLUSION:
      Prostate cancer was diagnosed in 2.34% of 3738 men who had their serum PSA levels
      measured, and in stage B two thirds had a positive diagnosis. PSA screening to
      detect prostate cancer as one of the health checks in Ikeda City was useful in
      detecting early prostate cancer.

PMID- 17025213
TI  - [The growing teratoma syndrome report of a case].
AB  - A 26-year-old man presented with a swelling of the right scrotal content, lumbago
      and exertional dyspnea. He underwent high inguinal orchiectomy. Histopathological
      examination of the specimen revealed yolk sac tumor and mature teratoma. Further
      evaluation revealed mediastinal and retroperitoneal lymph node metastases (stage
      IIIA). A single course of BEP (bleomysin, etoposide and cisplatin), two courses
      of chemotherapy consisting of nedaplatin and irinotecan, and three courses of TIP
      (paclitaxel, ifosfamide and cisplatin) were delivered. The previous abnormally
      elevated serum biomarkers (AFP, beta-hCG and LDH) returned to normal levels, but
      the mediastinal and retroperitoneal masses continued to enlarge slowly. The CT
      guided biopsy of the mediastinal mass was performed, and histologic study
      revealed no evidence of malignancy. He underwent excision of the mediastinal
      masses and retroperitoneal lymph node dissection. Histologic examination of the
      resected specimens revealed mature teratoma without malignant components. These
      results were compatible with growing teratoma syndrome. 30 months after the first
      excision of mediastinal mass, he underwent the second excision of recurrent
      mediastinal mass in the absence of biomarker elevation. The resected specimens
      revealed mature teratoma without malignant components. He is alive for 49 months
      after high inguinal orchiectomy and free of carcinoma.

PMID- 17025214
TI  - [A case of non-traumatic rupture of varicocele].
AB  - We report a case of a non-traumatic rupture of varicocele. A 28-year-old man
      visited our hospital complaining of left scrotal swelling with severe spontaneous
      pain of sudden onset after straining for defecation. MRI revealed a dilated
      spermatic cord with scrotal hematoma surrounding the left testis, which leads to
      the diagnosis of varicocele rupture. Conservative treatment with oral analgesics
      for a couple of weeks relieved the swelling and pain. Subinguinal microscopic
      ligation of left spermatic veins was performed 4 months later.

PMID- 17025215
TI  - [A case of seminoma with a low level positive of serum hCG (human chorionic
      gonadotropin) beta considered as false positive hCGbeta].
AB  - A 32-year-old male consulted a hospital with a complaint of left scrotal
      swelling. Serum hCGbeta and LDH levels were elevated and computed tomography
      demonstrated a suspicious small lymphadenopathy in the paraaortic region. Left
      inguinal orchiectomy was performed. Histological examination demonstrated
      seminoma. We diagnosed the disease as clinical stage 2A and the patient received
      2 courses of chemotherapy with cisplatin, etoposide and bleomycin. After this
      therapy, the small lymphadenopathy in the paraaortic region did not decrease in
      size. We considered this lesion a vessel or connective tissue. Although he
      achieved clinical complete remission and serum LDH level was normalized, the
      serum hCGbeta level remained low level positive. Urinary hCGbeta level after
      chemotherapy was below the threshold of detectability. We measured the serum from
      this patient as well as control sera by two- and four-fold dilution with a
      diluent comprised of mouse serum as a heterophilic antibody-blocking agent. The
      serum hCGbeta level of this patient was obviously decreased; in contrast, control
      sera were decreased in parallel. The serum hCGbeta level of this patient remained
      low level positive without recurrence for 8 months after chemotherapy. These
      results strongly suggested that low level of positivity for serum hCGbea in this
      case was a false positive finding. We consider the measurement of urinary hCGbeta
      and dilution measurement using a heterophilic antibody-blocking agent to be
      useful methods of distinguishing false positive findings for serum hCGbeta.

PMID- 17025216
TI  - [Introduction of proteomic approach to environmental medicine].
AB  - Recent progress in life science technology and the availability of much
      information on genes obtained by genome analysis has enabled us to analyze the
      changes of proteins on a large scale. Sets of proteins are called proteomes, and
      proteomics is the scientific field of proteome analysis including differential,
      post translational modification and interaction analyses. Various proteomic
      techniques, particularly two-dimensional gel electrophoresis (2-DE), mass
      spectrometry, protein chip methods, and surface plasmon resonance (SPR), are very
      useful for acquiring proteomes in cells, tissues and body fluid, and for
      analyzing interactions between a protein and other biofactors including proteins.
      A proteomic approach is also useful for determining biomarkers of diseases and
      key proteins involved in various stages of metabolism such as differentiation,
      cell cycle and apoptosis. Environmental pollutants including endocrine disruptors
      inhibit activities of various organs in wild animals and humans. Proteomic
      approaches could be very useful tools for elucidating the mechanisms of damage
      caused by environmental pollutants. In this review, we describe the application
      of a proteomic approach to the field of environmental medicine.

PMID- 17025217
TI  - [Study of relationships between state of mental health and indicators of medical
      expenses].
AB  - OBJECTIVE: The purpose of this study is to determine the relationships between
      the state of mental health and indicators of medical expenses for inpatient,
      outpatient and dental services. METHODS: This study was conducted using data from
      140 people (54 males and 86 females) who participated in a lifestyle intervention
      program. The result of General Health Questionnaire (GHQ)-30 survey performed in
      August 2003 was used as the indicator of mental health, whereas diagnoses based
      on International Classification of Diseases (ICD) 10 from medical expense claims
      in the 2003 fiscal year were used for disease classification by the Proportional
      Disease Magnitude (PDM) method. The subjects were classified into two groups by
      GHQ-30 score: low-score group (n=96) and high-score group (n=44). The differences
      between the two groups were compared by an unpaired t-test. RESULTS: For
      outpatient service in the high-score group, the medical expenses and the numbers
      of consulting days, medical expense claims and consultation cases at least two
      per month were significantly higher (p < 0.05) than those in the low-score group.
      However, there were no significant differences in the same indicators between
      inpatient and dental services. In the high-score group, the medical expenses of
      the XVIII group (symptoms, signs and abnormal clinical and laboratory findings,
      not elsewhere classified) of ICD10 were also significantly higher (p < 0.05) than
      those of the low-score group. CONCLUSIONS: The state of mental health is
      significantly associated with indicators of medical expenses for outpatient
      service. The medical expenses of a problematic non-mentally healthy group are
      significantly higher than those of a mentally healthy group.

PMID- 17025218
TI  - [Chronological analysis of disparities in numbers of ordinary hospital beds and x
      ray computed tomography scanners among secondary medical care sectors].
AB  - OBJECTIVE: In this study, we aimed at examining how disparities in selected
      medical care resources across secondary medical care sectors (SMCSs) changed over
      a twelve-year period following the introduction of the Medical Care Plan.
      METHODS: Changes in all SMCS boundaries prior to 2002 were identified from data
      published by the Ministry of Health and Welfare and prefectural governments. The
      per capita numbers of ordinary hospital beds and X-ray computed tomography (CT)
      scanners in hospitals were chosen as indicators of medical care resources,
      representing respectively mandatory and nonmandatory components of the Medical
      Care Plan. Their interquartile range and quartile variation coefficient were used
      as measures of disparity among SMCSs. RESULTS: The number of ordinary hospital
      beds per capita did not increase significantly between 1988 and 2000 in Group-A
      SMCSs (population density > or = 1000/km2) but increased significantly in Group-R
      (population density < 300/km2) and Group-U (300/km2 < or = population density <
      1000/km2) SMCSs. The disparity in the per capita numbers of hospital beds among
      all SMCSs however decreased as a whole. The per capita numbers of X-ray CT
      scanners increased significantly in all three groups of SMCSs between 1987 and
      1999. The coefficient of quartile variation for X-ray CT scanners remained larger
      than that for ordinary hospital beds over the 12-year period with the exception
      of Group-A SMCSs. CONCLUSIONS: The disparities in medical care resources among
      SMCSs decreased for ordinary hospital beds more markedly than for X-ray CT
      scanners, possibly as an effect of the implementation of the Medical Care Plan.

PMID- 17025219
TI  - [Odor stick identification test for Japanese patients with olfactory
      disturbances].
AB  - In recent years, a new stick-type odor identification test, the odor-stick
      identification test for Japanese (OSIT-J) has been developed in Japan. Thirteen
      odors familiar to Japanese people are used in this test. The OSIT-J is an
      olfactory discrimination test and is significantly correlated with the average
      recognition threshold of T & T olfactometry, which is the standard olfactory
      acuity test used in Japan. In this study, we evaluated the accuracy of the OSIT-J
      in patients with olfactory disturbances. We compared the OSIT-J and T & T
      olfactometry results and examined the sensitivity and specificity of the OSIT-J.
      Using the OSIT-J, olfactory disturbances were diagnosed in more than 70% based on
      the average recognition threshold determined by T & T olfactometry. OSIT-J is a
      simple test and is recommended for use in clinical practice for evaluating
      olfactory disturbances.

PMID- 17025220
TI  - [Treatment of Henoch-Schonlein purpura nephritis in children with tonsillectomy].
AB  - Henoch-Schonlein purpura nephritis (HSPN) is an important complication of Henoch
      Sch6nlein purpura (HSP). Pathological findings in the kidney are similar to those
      for IgA nephritis, which is characterized by the deposition of IgA immune complex
      in the glomerular mesangium. Since a tonsillectomy is useful for IgA nephritis,
      this procedure holds great promise for the treatment HSPN. In the present study,
      we assessed the effectiveness of a tonsillectomy in children with HSPN whose
      conditions could not be controlled by medication, including predonisone and
      cyclophosphamide. Seven patients (four boys and three girls) with histologically
      well-defined HSPN who had undergone a tonsillectomy between 1998 and 2000 and who
      had been followed for more than 6 postoperative months were retrospectively
      examined. The age of the patients ranged between 3 and 13 years (average, 7.6 +/-
      3.2 years) at the time of operation. Postoperative changes in urinary data were
      assessed according in the severity of the pathological findings in the kidney and
      the patient's clinical condition. The severity of the pathological findings in
      the kidney was determined based on the classification of the International Study
      of Kidney Disease (ISKDC) and the Index of Glomeruler Lesion (IGL). All patients
      examined in the present study had an ISKDC classification of over grade II. One
      patient had a grade IV classification, 3 had a grade III classification, and 3
      had a grade II classification. The patients were placed in one of five clinical
      groups: (1) nephritic-nephrotic syndrome, (2) acute nephritic syndrome, (3)
      nephritic syndrome, (4) over 1 g/day of proteinuria without hypoalbuminemia or
      oedema, or 5) below 1 g/day of proteinuria with or without hematuria. One patient
      was classified in group 1, 1 was group classified in 2, 2 were classified in
      group 3, 2 were classified in group 4 and 1 was classified in group 5. The mean
      observation period was 74 +/- 6.4 months. The hematuria and proteinuria resolved
      in all patients, regardless of their preoperative pathological or clinical
      severity, within 12 postoperative months. During the observation period, no
      relapse was observed. Moreover, all medication, including steroid use, was
      stopped within the observation period. Therefore, a tonsillectomy was considered
      to be effective for the treatment of children with HSPN whose conditions cannot
      be controlled using medication.

PMID- 17025221
TI  - [Case of toxic shock-like syndrome affecting the neck].
AB  - Toxic shock-like syndrome (TSLS) is a form of rapidly progressing septic shock
      that can lead to multiple organ failure and has a high mortality rate of 30%. We
      report a rare case of TSLS affecting the head and neck. A 40-year-old man
      complained of redness and swelling of the neck with vomiting and diarrhea. His
      blood pressure dropped, and multiple organ failure occurred. Streptcoccus
      pyogenes, Group A, was identified in a blood culture, and he was diagnosed as
      having TSLS. He was treated with high-dose carbapenem, clindamysin, and gamma
      globulin. Continuous hemodiafiltration (CHDF) and PMX-DHP was applied to prevent
      sepsis and multiple organ failure. Debridement of the neck was performed on day
      16. He recovered gradually and was discharged from hospital on day 45. A total
      resection is required to treat TSLS, but such a procedure is difficult to perform
      in the head and neck region. Our case improved without resection but after
      debridement and general control. TSLS should be first treated by medication and
      then by surgery, consisting of either debridement or resection.

PMID- 17025222
TI  - [Photodynamic therapy for age-related macular degeneration].

PMID- 17025223
TI  - [The effect of Sairei-to on oxygen-induced retinal neovascularization in the
      neonatal rat].
AB  - PURPOSE: To study the effect of Sairei-to (ST), a Japanese traditional medicine,
      on oxygen-induced retinopathy (OIR) in rats. METHODS: OIR was induced by
      maintaining Sprague-Dawley neonatal rats in 80% oxygen for 12 days. The rats were
      treated once daily with oral administration of 0.75 g/kg (n = 9), 1.5 g/kg (n =
      13) of ST in water, or water alone (WA, n = 13) at 5 mL/ kg body weight from day
      6 to day 17. On day 18, retinal samples were collected. Retinal
      neovascularization (NV) was assessed by the NV score, and by the percentage of
      avascular area (% AVA), using a method previously reported. The number of severe
      retinal NV cases (NV > or = 9) was compared. The retinal vascular endothelial
      growth factor (VEGF) concentrations were measured with an immunoassay kit, at 0,
      12, 24, 72 and 144 hours after oxygenation. RESULTS: NV score and % AVA decreased
      in the ST treated group compared to the WA group. However, severe NV was seen in
      five cases of WA and in one case of the ST treated group. Thus severe NV was
      inhibited significantly by ST treatment (p = 0.0185). Retinal VEGF did not differ
      between groups at any time points. CONCLUSION: These data suggest that severe NV
      in OIR is inhibited by ST treatment.

PMID- 17025224
TI  - [Blurred vision after instillation of topical carbonic anhydrase inhibitor].
AB  - PURPOSE: The aim of this study was to compare brinzolamide with dorzolamide in
      regard to blurred vision after instillation. We also compared saline with two
      topical carbonic anhydrase inhibitor drugs. SUBJECTS AND METHODS: The study
      population comprised 21 healthy volunteers whose best corrected visual acuity was
      1.0 or better. Brinzolamide 1% or dorzolamide 1% was applied to one eye the
      contralateral eye was exposed to the other drug. At 30 sec after instillation,
      visual acuity was measured every 30 sec until best visual acuity was recovered.
      Because visual acuity can fluctuate widely with blinking, subjects blinked for 5
      sec before visual acuity measurement. As control, we applied saline alone to both
      eyes of 14 subjects and measured the change in visual acuity in the same way.
      Subjective sensations in each eye were recorded after measurement. RESULTS:
      Average visual acuity every 30 sec for 5 min was 0.41, 0.56, 0.68, 0.86, 0.87,
      0.96, 1.04, 1.08, 1.11, and 1.12 after dorzolamide instillation, and 0.28, 0.42,
      0.60, 0.69, 0.81, 0.91, 0.93, 0.99, 1.06, and 1.10 after brinzolamide
      instillation. In contrast, the average visual acuity after saline instillation
      for 2 min was 1.09, 1.13, 1.16 and 1.16. Of the 21 subjects, 15 (71.4%) felt
      moderate or severe irritation when dorzolamide was instilled; 2 (9.5%) felt
      moderate or severe irritation when brinzolamide was instilled. CONCLUSIONS: Both
      brinzolamide and dorzolamide caused significantly prolonged blurring of vision,
      from 30 sec to 2 or 3 min after instillation, as compared with saline only. The
      average visual acuity after brinzolamide instillation was lower than after
      dorzolamide for 5 min after instillation, although there was no significant
      difference. Judging from the subjects' sensations, it is suggested that with
      dorzolamide the prolonged blurred vision was due to reflex tearing from
      irritation, as explained above, whereas with brinzolamide it was due to opaque
      tears on the ocular surface.

PMID- 17025225
TI  - [The influence on the static visual field of peripapillary chorioretinal atrophy-
      relation to refractive error].
AB  - PURPOSE: To investigate the influence of refractive error on white-on-white
      perimetry(W-on-W) in myopic subjects according to the presence or absence of
      peripapillary chorioretinal atrophy (PPA). SUBJECTS AND METHODS: W-on-W perimetry
      was performed on 57 normal volunteers whose fundus photography was clear and the
      presence or absence of PPA was distinct. We divided the 57 normal volunteers into
      a PPA-positive group and a PPA-negative group, and investigated the influence of
      refractive error. RESULTS: Mean deviation (MD) reduction was significantly
      correlated with the degree of myopia in the myopic group, whereas there was no
      significant correlation with refractive error in the control group. In the myopic
      group, MD reduction was significantly correlated with the degree of myopia in the
      PPA-positive group, whereas there was no significant correlation between
      refractive error and MD in the PPA-negative group. In the control group, there
      was no significant correlation between refractive error and MD in either the PPA
      positive group or the PPA-negative group. CONCLUSIONS: MD reduction was
      significantly correlated with the degree of myopia in myopic subjects, and was
      more remarkable in PPA-positive subjects.

PMID- 17025226
TI  - [Ocular complications in patients with human immunodeficiency virus infection].
AB  - PURPOSE: To evaluate the recent clinical manifestations of ocular complications
      in patients with human immunodeficiency virus(HIV) infection. METHODS: We
      retrospectively reviewed the medical records of 94 new HIV-positive patients
      examined at the International Medical Center of Japan between April 1, 2002, and
      March 31, 2003, and listed the details of ocular complications. The use of highly
      active antiretroviral therapy (HAART) and CD 4 cell counts was also recorded in
      patients with cytomegalovirus (CMV) retinitis and iritis/vitritis. RESULTS: The
      following ocular complications were recognized in 31 patients: retinal
      microvasculopathy (11 cases), CMV retinitis (10 cases), inactive inflammatory
      changes (6 cases), iritis/vitritis (5 cases), optic nerve atrophy (2 cases),
      papilledema (2 cases), ocular tuberculosis (1 case), progressive outer retinal
      necrosis (1 case) and conjunctival Kaposi's sarcoma (1 case). In patients with
      CMV retinitis, the CD 4 cell counts at the onset were lower than 50/microl except
      in 1 case. Iritis and/or vitritis were recognized in 5 cases, and the onset of 4
      cases occurred after the beginning of HAART. Among the patients studied, immune
      recovery uveitis was suspected in 3 patients with a history of CMV retinitis.
      CONCLUSIONS: Ocular complications were recognized in almost one third of the
      patients in our series. Immune recovery uveitis was suspected in 3 patients with
      iritis/vitritis who previously had CMV retinitis.

PMID- 17025227
TI  - [Clinical effects of photodynamic therapy with Verteporfin for age-related
      macular degeneration 1: three-month results].
AB  - PURPOSE: To evaluate the 3-month effects after one-time photodynamic therapy
      (PDT) for subfoveal choroidal neovascularization (CNV) in age-related macular
      degeneration (AMD). SUBJECTS AND METHODS: The subjects were 122 patients with
      subfoveal CNV due to AMD detected by fluorescein angiography (FA). FA,
      indocyanine-green angiography (IA), and the examination of visual acuity were
      done before and 3 months after PDT. The diameter of CNV in FA was compared, and
      ophthalmological examination before the treatment determined whether there were
      any factors associated with a reduction or suppression of CNV. RESULTS: 3 months
      after PDT, 89 eyes had a significant (p < 0.001) reduction of CNV (41 eyes had
      blockage of CNV). In case of polypoidal choroidal vasculopathy (PCV) detected by
      IA, CNV was significantly reduced compared with the effects of other types of
      therapy (p = 0.032). Moreover, CNV was blocked significantly when fibrin tissue
      was present on a part of CNV before treatment (p = 0.026). Visual acuity was
      maintained or improved in 96 eyes. CONCLUSION: One-time PDT was effective in
      reducing or suppressing CNV as confirmed by FA.

PMID- 17025228
TI  - [Assessment of the quality of life of patients with age-related macular
      degeneration after photodynamic therapy].
AB  - OBJECTIVE: To quantify quality of life (QOL) changes in patients who have
      received a single session of photodynamic therapy (PDT) for subfoveal choroidal
      neovascularization, secondary to age-related macular degeneration (AMD), and to
      identify factors that correlate with the QOL changes. METHODS: The QOL changes in
      88 patients with AMD were scored with the 25-Item National Eye Institute Visual
      Function Questionnaire (VFQ-25) before and 3 months after a single PDT with
      routine ophthalmologic examinations. We used multiple regression analysis to
      evaluate VFQ-25 sub-scale scores and ophthalmologic findings in these patients
      before PDT, to identify impact on the effectiveness of PDT. We also evaluated
      changes in ophthalmologic findings influencing the QOL score. RESULTS: The sub
      scale scores for both 'mental health' (p = 0.02) and 'role limitation' (p = 0.03)
      improved significantly in all 88 cases, but only 'mental health' improved
      significantly in 34 cases in which PDT was effective. Multiple regression
      analysis in all 88 cases revealed that the factors contributing significantly to
      improvement in 'mental health' were a lower pre-PDT 'mental health' score (p <
      0.01) and the presence of fibrous tissue (p = 0.01) before the PDT session. The
      lower the role limitation before PDT (p < 0.01), the more significant was the
      improvement in this score. CONCLUSION: Although no baseline sub-scale score was
      identified as predicting the effectiveness of a single PDT session, the scores
      for both 'mental health' and 'role limitation' improved.

PMID- 17025229
TI  - [Long-term effects of isopropyl unoprostone monotherapy on intraocular pressure
      and visual field for normal-tension glaucoma and primary open-angle glaucoma
      patients].
AB  - We retrospectively investigated the long-term effects of isopropyl unoprostone
      monotherapy on intraocular pressure and visual field for normal-tension glaucoma
      and primary open-angle glaucoma patients. Among 80 eyes of 49 subjects receiving
      isopropyl unoprostone monotherapy for 2 years or more, 32 eyes of 32 subjects
      were analyzed because of the good reliability of their visual acuity and visual
      field (age, 68.1 +/- 10.1 yrs, follow-up period 47.8 +/- 14.7 months). The mean
      values of intraocular pressure and visual field indices were compared with
      baseline data before medication. The visual field changes were also analyzed
      using the Kaplan-Meier life-table method. The mean intraocular pressure decreased
      for 4 years from 14.7 +/- 4.3 mmHg (mean +/- SD) at baseline, to 12.7 +/- 4.4mmHg
      at 4 years. The global index of visual field (mean defect, loss variance) did not
      change significantly during the 4 years. The accumulative probability of survival
      was 80.7 +/- 8.0% after 4 years when the endpoint was defined as 3dB progression
      in mean defect. Isopropyl unoprostone might have the possibility of stabilizing
      the visual field for a long period of time.

PMID- 17025230
TI  - [Evaluation of the chemokine variation in tears of contact lens wearers].
AB  - PURPOSE: To evaluate the variation of chemokines in tears of contact lens
      wearers. SUBJECTS AND METHODS: The subjects were divided into the three groups: a
      control group consisting of 26 eyes of 26 healthy volunteers without contact
      lenses a contact lens group (CL group) consisting of 30 eyes of 30 healthy
      contact lens wearers without ocular surface disorders, and a giant papillary
      conjunctivitis group (GPC group) consisting of 9 eyes of 9 patients with giant
      papillary conjunctivitis caused by contact lens wearing. Tear samples were taken
      by the modified Schirmer I method using a filter paper. Tear samples were eluted
      and analyzed for chemokines including interleukin-8 (IL-8), eotaxin-2, and
      pulmonary and activation-regulated CC chemokine (PARC) by the antibody array
      method. Concentrations of IL-8, eotaxin-2, and PARC in tears were determined
      quantitatively by enzyme-linked immunosorbent assay (ELISA). RESULTS: Using the
      antibody array method, the expression of IL-8, eotaxin-2, and PARC in the GPC
      group was 4-fold higher or greater than in the control group. In the measurement
      by ELISA, IL-8 levels in the GPC group (1154.5 +/- 1739.3 pg/ml) (mean +/- SD)
      were significantly higher (Kruskal-Wallis test, p < 0.01) than in the control
      (75.2 +/- 88.7 pg/ml) and CL (153.6 +/- 252.8 pg/ml) groups. The eotaxin-2 levels
      in tears did not show a statistical difference among the three groups. The PARC
      level in tears of the GPC group (2859.6 +/- 2299.9 pg/ml) was significantly
      higher than in the control(589.0 +/- 324.8 pg/ml) and CL (671.7 +/- 536.2 pg/ml)
      groups (Kruskal-Wallis test, p < 0.05). CONCLUSION: Wearing a contact lens per se
      disorders, does not cause chemokine variation in tears. However, an increase of
      IL-8 which induces neutrophilic invasion and an increase of PARC which induces
      lymphocyte invasion play an important roles in increasing the risk factor of GPC
      when wearing contacts.

PMID- 17025231
TI  - [A case of posterior scleritis associated with extensive retinochoroidal
      atrophy].
AB  - BACKGROUND: Posterior scleritis is known to exhibit various changes in the ocular
      fundus, but retinochoroidal atrophy is a rare complication. CASE: A 54-year-old
      man presented with the complaint of blurred vision in the right eye. The patient
      had visited our clinic twice before, 22 and 11 years earlier. Although his
      funduscopic findings had demonstrated choroidal detachment in both eyes, the
      cause could not be determined at that time. FINDINGS: His visual acuity was
      20/200, OD and 20/100, OS. Funduscopic examination showed annual choroidal
      detachments and geographic retinochoroidal atrophy in the posterior pole OU, and
      serous retinal detachment OD. B-scan ultrasonograpy revealed diffuse thickening
      and flattening of the posterior coats of the eye, and orbital enhanced computed
      tomography revealed thickening and enhancement of the posterior sclera. A
      diagnosis of posterior scleritis was made. Prednisolone 80 mg/ day was initiated
      and gradually tapered. Nine months later choroidal and serous retinal detachment
      were resolved. CONCLUSION: We encountered a rare case of posterior scleritis with
      associated extensive retinochoroidal atrophy. We speculated that the cause was
      inflammation of the retina and choroid, and accumulation of subretinal fluid for
      a long period.

PMID- 17025233
TI  - [Leukotriene B4 and its receptors].

PMID- 17025232
TI  - [Calcification on the posterior surface of an implanted silicone intraocular lens
      in a patient with asteroid hyalosis].
AB  - BACKGROUND: Calcification on the surface of the hydrogel intraocular lens (IOL)
      has been reported, but the mechanism of the surface calcification is not fully
      understood. We report a case of surface calcification on an implanted silicone
      IOL. The purpose of our study was to examine the clinical and ultrastructural
      findings associated with the late surface calcification of a silicone IOL. CASE:
      A 70-year-old Japanese man had undergone cataract surgery in his left eye, with
      uneventful phacoemulsification and silicone IOL (Allergan SI-55 NB) implantation
      with the manufacturer's cartridge and injector. He was referred again 29 months
      later with blurred vision, glare sensitivity, and decreased vision in his left
      eye. He was diagnosed as having aftercataract. Although YAG laser capsulotomy was
      performed, the opacity on the posterior surface gradually increased. The opacity
      was located mainly within the capsulotomy window on the posterior surface of the
      lens, although the patient maintained good visual acuity. LV : 0.2 (1.0 x S-2.0
      D). The lens was removed 46 months after the initial surgery. Scanning electron
      microscopy (SEM) showed membranous deposits on the posterior optical surface of
      the silicone lens. There were high levels of phosphoric acid (P) and calcium (C)
      confirming calcification of the silicone IOL. Asteroid hyalosis was observed in
      the fellow eye of the patient. CONCLUSION: This is the first report of surface
      calcification of a silicone IOL in Japan. Although the mechanism of the
      calcification has not been determined, careful clinical follow-up of patients
      implanted with silicone lenses is necessary to determine if this phenomenon is
      rare and sporadic or if it may be more widespread. Since 5 similar cases of
      calcification in silicone lenses with accompanying asteroid hyalosis have been
      reported in other countries, we can conclude that silicone lens implantation in
      eyes with asteroid hyalosis should be avoided.

PMID- 17025234
TI  - [Legionella and its infection].

PMID- 17025236
TI  - 5-methyl-pyrrolidinone chitosan films as carriers for buccal administration of
      proteins.
AB  - The purpose of this research was to investigate 5-methyl-pyrrolidinone chitosan
      (MPC) films as carriers for buccal delivery of protein drugs. Placebo and protein
      loaded MPC films were prepared by casting and were then cross-linked with
      tripolyphosphate at different pH conditions. Myoglobin (MHb) was chosen as the
      model protein because its molecular weight is under the permeability limit of the
      buccal mucosa. The observed characteristics like bioadhesiveness, swelling
      behavior, and in vitro release of MHb from loaded films furnish information on
      the functional behavior of these films. The results obtained show that the
      modulation of MHb release was achieved only through chitosan cross-linking; the
      best results in release rate control were obtained by cross-linking performed at
      pH 6.5. Good bioadhesion properties were maintained even with high cross-linking
      degrees; the swelling index of MHb-loaded films at different cross-linking
      degrees evaluated at pH 7.4 and pH 6.4 were comparable to those of placebo films.
      By setting suitable tripolyphosphate cross-linking conditions for MPC films, one
      can control protein release without affecting bioadhesion.

PMID- 17025237
TI  - Osmotic flow through asymmetric membrane: a means for controlled delivery of
      drugs with varying solubility.
AB  - A nondisintegrating, controlled release, asymmetric membrane capsular system of
      flurbiprofen was developed and evaluated for controlled release of the drug to
      overcome some of its side effects. Asymmetric membrane capsules were prepared
      using fabricated glass mold pins by phase inversion process. The effect of
      different formulation variables was studied based on 2(3) factorial design;
      namely, level of osmogen, membrane thickness, and level of pore former. Effects
      of polymer diffusibility and varying osmotic pressure on drug release were also
      studied. Membrane characterization by scanning electron microscopy showed an
      outer dense region with less pores and an inner porous region for the prepared
      asymmetric membrane. Differential scanning calorimetry studies showed no
      incompatibility between the drug and the excipients used in the study. In vitro
      release studies for all the prepared formulations were done (n = 6). Statistical
      test (Dunnett multiple comparison test) was applied for in vitro drug release at
      P > .05. The best formulation closely corresponded to the extra design checkpoint
      formulation by a similarity (f2) value of 92.94. The drug release was independent
      of pH but dependent on the osmotic pressure of the dissolution medium. The
      release kinetics followed the Higuchi model and the mechanism of release was
      Fickian diffusion.

PMID- 17025239
TI  - Compaction characteristics of ethylcellulose in the presence of some channeling
      agents: technical note.

PMID- 17025238
TI  - Effect of formulation factors on in vitro transcorneal permeation of gatifloxacin
      from aqueous drops.
AB  - The purpose of this research was to optimize the formulation factors for maximum
      in vitro permeation of gatifloxacin from aqueous drops through excised goat
      cornea and to evaluate the permeation characteristics of drug from selected
      marketed eyedrop formulations. Permeation studies were conducted by putting 1 mL
      of formulation on the cornea (0.67 cm(2)) fixed between the donor and receptor
      compartments of an all-glass modified Franz diffusion cell and measuring
      gatifloxacin concentration in the receptor (containing normal saline under
      stirring) by spectrophotometry at 291.5 nm, after 120 minutes. Raising the drug
      concentration of the drops increased the drug permeation but decreased the
      percent permeation and the in vitro ocular availability. Raising the pH of the
      formulation from pH 5 to 7.2 increased both the drug permeation and the in vitro
      ocular availability. Eyedrops containing benzalkonium chloride (BAK; 0.01%
      wt/vol) and disodium edetate (EDTA; 0.01% wt/vol) showed maximum permeation,
      followed by Zymar, BAK (0.01% wt/vol), Gatilox, Gatiquin, and Gate (statistically
      significant P < .05 compared with control). In vitro titration of the
      formulations with 0.1N NaOH indicated the presence of a buffer in Zymar (pH 6)
      and Gate (pH 5.8), which may cause irritation and induce lacrimation, resulting
      in reduced ocular availability in vivo. Thus, formulation with BAK and EDTA,
      which is unbuffered, has a better likelihood of being absorbed in vivo. The BAK
      EDTA formulation significantly (P < .05) increased the permeation of gatifloxacin
      through paired excised corneas of goat, sheep, and buffalo, compared with the
      control formulation. The goat cornea showed the greatest increase in permeation,
      followed by the sheep and buffalo corneas.

PMID- 17025240
TI  - Acoustic-resonance spectrometry as a process analytical technology for the
      quantification of active pharmaceutical ingredient in semi-solids.
AB  - The purpose of this study was to demonstrate acoustic resonance spectrometry
      (ARS) as an alternative process analytical technology to near infrared (NIR)
      spectroscopy for the quantification of active pharmaceutical ingredient (API) in
      semi-solids such as creams, gels, ointments, and lotions. The ARS used for this
      research was an inexpensive instrument constructed from readily available parts.
      Acoustic-resonance spectra were collected with a frequency spectrum from 0 to
      22.05 KHz. NIR data were collected from 1100 to 2500 nm. Using 1-point net
      analyte signal (NAS) calibration, NIR for the API (colloidal oatmeal [CO]) gave
      an r2 prediction accuracy of 0.971, and a standard error of performance (SEP) of
      0.517%CO. ARS for the API resulted in an r2 of 0.983 and SEP of 0.317%CO. NAS
      calibration is compared with principal component regression. This research
      demonstrates that ARS can sometimes outperform NIR spectrometry and can be an
      effective analytical method for the quantification of API in semi-solids. ARS
      requires no sample preparation, provides larger penetration depths into lotions
      than optical techniques, and measures API concentrations faster and more
      accurately. These results suggest that ARS is a useful process analytical
      technology (PAT).

PMID- 17025241
TI  - Vacuum foam drying for preservation of LaSota virus: effect of additives.
AB  - The purpose of this research was to apply vacuum foam drying (VFD) for processing
      of LaSota virus and to screen formulation additives for its stability. The
      aqueous dispersion of harvest containing sucrose or trehalose in combination with
      additive (monosaccharides, polymers, N-Z-amine) was prepared. The diluted
      dispersions in vials were vacuum concentrated, foamed to form a continuous
      structure, and vacuum dried. The products were evaluated for foam
      characteristics, residual moisture, virus titer, x-ray diffraction pattern, and
      stability profile. The foamability increased with solid content in solutions. The
      foamability of sucrose was enhanced with incorporation of N-Z-amine (10% and 15%
      wt/vol) and polyvinyl pyrrolidone (PVP K30, 3% wt/vol). The fructose- or
      galactose-containing mixtures were deposited irregularly on the vial surface. The
      virus titer increased with disaccharides in the formulation. Sucrose provided
      better protection than trehalose. Unlike lyophilization, N-Z-amine with sucrose
      protected the virus from Millard's Browning. Amino acids do not have a catalytic
      effect on hydrolysis of sucrose during VFD. Monosaccharides were ineffective. A
      synergistic effect of PVP K30 or polyethylene glycol 6000 (3% wt/vol) with N-Z
      amine provided the maximum virus titer (6.97 and 7.15, respectively). This
      formulation retained the desired virus potency at 5 degrees , 25 degrees , and 40
      degrees C. The diffraction pattern revealed that a threshold concentration of N-Z
      amine was required for inhibiting crystallization of sucrose during VFD. VFD was
      successfully applied to produce a solid LaSota formulation. The products were
      amorphous and did not devitrify on storage.

PMID- 17025242
TI  - Formulation of anastrozole microparticles as biodegradable anticancer drug
      carriers.
AB  - The purpose of this study was to develop poly(d,l-lactic-co-glycolic acid) (PLGA)
      based anastrozole microparticles for treatment of breast cancer. An
      emulsion/extraction method was used to prepare anastrozole sustained-release PLGA
      based biodegradable microspheres. Gas chromatography with mass spectroscopy
      detection was used for the quantitation of the drug throughout the studies.
      Microparticles were formulated and characterized in terms of encapsulation
      efficiency, particle size distribution, surface morphology, and drug release
      profile. Preparative variables such as concentrations of stabilizer, drug-polymer
      ratio, polymer viscosity, stirring rate, and ratio of internal to external phases
      were found to be important factors for the preparation of anastrozole-loaded PLGA
      microparticles. Fourier transform infrared with attenuated total reflectance
      (FTIR-ATR) analysis and differential scanning calorimetry (DSC) were employed to
      determine any interactions between drug and polymer. An attempt was made to fit
      the data to various dissolution kinetics models for multiparticulate systems,
      including the zero order, first order, square root of time kinetics, and biphasic
      models. The FTIR-ATR studies revealed no chemical interaction between the drug
      and the polymer. DSC results indicated that the anastrozole trapped in the
      microspheres existed in an amorphous or disordered-crystalline status in the
      polymer matrix. The highest correlation coefficients were obtained for the
      Higuchi model, suggesting a diffusion mechanism for the drug release. The results
      demonstrated that anastrozole microparticles with PLGA could be an alternative
      delivery method for the long-term treatment of breast cancer.

PMID- 17025243
TI  - Removal of peroxides in polyethylene glycols by vacuum drying: implications in
      the stability of biotech and pharmaceutical formulations.
AB  - The purpose of this study was to investigate the utility of vacuum drying for
      removing peroxides from polyethylene glycols (PEGs). PEG solutions (PEG 1450 and
      PEG 20000) containing varying levels of peroxides were prepared by storing under
      different light and temperature conditions. PEGs containing low and high levels
      of peroxides were vacuum dried from dilute and concentrated solutions (2.5%,
      7.5%, 15%, and 50% wt/vol of PEG 1450 and 2.5%, 7.5%, 15%, and 25% wt/vol of PEG
      20000). Ferrous ion oxidation in presence of ferric ion indicator xylenol orange
      (FOX) colorimetric assay was used to determine the concentration of peroxides.
      Peroxide content in PEGs increased upon storage. The increase was more pronounced
      when PEGs were stored at higher temperatures and exposed to light. Vacuum drying
      at 0.1 mm Hg for 48 hours at 25 degrees C resulted in greater than 90% decrease
      in the level of peroxides in all cases except when high peroxide containing 25%
      wt/vol solution of PEG 20000 or 50% wt/vol solution of PEG 1450 were dried. The
      reduction in the level of peroxides for PEGs dried from high peroxide containing
      25% wt/vol solution of PEG 20000 and 50% wt/vol solution of PEG 1450 was found to
      be 88% and 52%, respectively. Oxidation of methionine in Met-Leu-Phe peptide was
      significantly reduced when vacuum-dried PEGs were used. Vacuum drying PEG
      solutions at low pressures is an effective method for the removal of the residual
      peroxides present in commercially available PEGs.

PMID- 17025244
TI  - Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used
      for film coating.
AB  - The aim of the present study was to prepare surfactant-free pseudolatexes of
      various methacrylic acid copolymers. These aqueous colloidal dispersions of
      polymeric materials for oral administration are intended for film coating of
      solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate
      dispersions were produced by an emulsification-diffusion method involving the use
      of partially water-miscible solvents and the mutual saturation of the aqueous and
      organic phases prior to the emulsification in order to reduce the initial
      thermodynamic instability of the emulsion. Because of the self-emulsifying
      properties of the methacrylic acid copolymers, it was possible to prepare aqueous
      dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and
      E using 2-butanone or methyl acetate as partially water-miscible solvents, but
      without any surfactant. However, in the case of the cationic Eudragit E,
      protonation of the tertiary amine groups by acidification of the aqueous phase
      was necessary to improve the emulsion stability in the absence of surfactant and
      subsequently to prevent droplet coalescence during evaporation. In addition, a
      pseudolatex of Eudragit E was used to validate the coating properties of the
      formulation for solid dosage forms. Film-coated tablets of quinidine sulfate
      showed a transparent glossy continuous film that was firmly attached to the
      tablet. The dissolution profile of quinidine sulfate from the tablets coated with
      the Eudragit E pseudolatex was comparable to that of tablets coated with an
      acetonic solution of Eudragit E. Furthermore, both types of coating ensured
      similar taste masking. The emulsification-evaporation method used was shown to be
      appropriate for the preparation of surfactant-free colloidal dispersions of the 3
      types of preformed methacrylic acid copolymers; the dispersions can subsequently
      be used for film coating of solid dosage forms.

PMID- 17025245
TI  - Evaluation of alternative strategies to optimize ketorolac transdermal delivery.
AB  - In the present study, 2 alternative strategies to optimize ketorolac transdermal
      delivery, namely, prodrugs (polyoxyethylene glycol ester derivatives, I-IV) and
      nanostructured lipid carriers (NLC) were investigated. The synthesized prodrugs
      were chemically stable and easily degraded to the parent drug in human plasma.
      Ketorolac-loaded NLC with high drug content could be successfully prepared. The
      obtained products formulated into gels showed a different trend of drug
      permeation through human stratum corneum and epidermis. Particularly, skin
      permeation of ester prodrugs was significantly enhanced, apart from ester IV,
      compared with ketorolac, while the results of drug release from NLC outlined that
      these carriers were ineffective in increasing ketorolac percutaneous absorption
      owing to a high degree of mutual interaction between the drug and carrier lipid
      matrix. Polyoxyethylene glycol esterification confirmed to be a suitable approach
      to enhance ketorolac transdermal delivery, while NLC seemed more appropriate for
      sustained release owing to the possible formation of a drug reservoir into the
      skin.

PMID- 17025246
TI  - Estimation of intramolecular cyclization activation energies via isothermal
      gravimetric analysis: a technical note.

PMID- 17025247
TI  - Chitosan lactate as a nonviral gene delivery vector in COS-1 cells.
AB  - The purpose of this research was to evaluate chitosan lactate (CL) of different
      molecular weights (MWs) as a DNA complexing agent for its efficiency in
      transfecting COS-1 cells (green monkey fibroblasts) and its effect on cell
      viability compared with polyethylenimine (PEI), a commercially available cationic
      polymer. CL and chitosan base dissolved in dilute acetic acid (chitosan acetate
      [CA]) of different MWs (20, 45, 200, 460 kDa) and N/P ratios (2:1, 4:1, 8:1,
      12:1, 24:1) formed complexes with pSV beta-galactosidase plasmid DNA. The
      complexes were characterized by agarose gel electrophoresis and investigated for
      their ability to transfect COS-1 cells compared with PEI. Additionally, the
      effect of CL on the viability of COS-1 cells was investigated using 3-(4,5
      dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The binding of
      CL/DNA and CA/DNA was dependent on chitosan MWs. The N/P ratio of CL to
      completely form the complex with the DNA was higher than that of CA. Both CL and
      CA were comparable in transfection efficiencies at an N/P ratio of 12:1, but less
      efficient than PEI (P < .05). The cell viability in the presence of CL and CA at
      all MWs was over 90%, whereas that of PEI-treated cells was approximately 50%.
      These results suggest the advantage of CL for in vitro gene transfection, with
      the ease of preparation of polymer/DNA complexes and low cytotoxicity.

PMID- 17025248
TI  - Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan.
AB  - The purpose of the present study was to develop intranasal delivery systems of
      sumatriptan using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive
      polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation
      temperature below 34 degrees C to ensure gelation at physiological temperature
      after intranasal administration. Gelation temperature was determined by physical
      appearance as well as by rheological measurement. The gelation temperatures of
      the formulations decreased by addition of increasing concentrations of Carbopol
      (ie, from 29 degrees C for 18% PF127 to 23.9 degrees C for 18% PF127, 0.5%
      Carbopol). The mucoadhesive force in terms of detachment stress, determined using
      sheep nasal mucosal membrane, increased with increasing concentration of
      Carbopol. The results of in vitro drug permeation studies across sheep nasal
      mucosa indicate that effective permeation coefficient could be significantly
      increased by using in situ gelling formulation with Carbopol concentration 0.3%
      or greater. Finally, histopathological examination did not detect any damage
      during in vitro permeation studies. In conclusion, the PF127 gel formulation of
      sumatriptan with in situ gelling and mucoadhesive properties with increased
      permeation rate is promising for prolonging nasal residence time and thereby
      nasal absorption.

PMID- 17025249
TI  - Enhancement of dissolution profile by solid dispersion (kneading) technique.
AB  - This article investigates enhancement of the dissolution profile of valdecoxib
      using solid dispersion with PVP. The article also describes the preparation of
      fast-dissolving tablets of valdecoxib by using a high amount of
      superdisintegrants. A phase solubility method was used to evaluate the effect of
      various water-soluble polymers on aqueous solubility of valdecoxib. Polyvinyl
      pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the
      method of kneading. Dissolution studies using the USP paddle method were
      performed for solid dispersions of valdecoxib. Infrared (IR) spectroscopy,
      differential scanning calorimetry (DSC), and x-ray diffractometry (XRD) were
      performed to identify the physicochemical interaction between drug and carrier,
      hence its effect on dissolution. Tablets were formulated containing solid
      dispersion products and compared with commercial products. IR spectroscopy, XRD,
      and DSC showed no change in the crystal structure of valdecoxib. Dissolution of
      valdecoxib improved significantly in solid dispersion products (< 85% in 5
      minutes). Tablets containing solid dispersion exhibited better dissolution
      profile than commercial tablets. Thus, the solid dispersion technique can be
      successfully used for improvement of dissolution of valdecoxib.

PMID- 17025250
TI  - Graphical comparison of image analysis and laser diffraction particle size
      analysis data obtained from the measurements of nonspherical particle systems.
AB  - The purpose of this paper is to describe results from the use of a set of Excel
      macros written to facilitate the comparison of image analysis (IA) and laser
      diffraction (LD) particle size analysis (psa) data. Measurements were made on
      particle systems of differing morphological characteristics including differing
      average aspect ratios, particle size distribution widths and modalities. The IA
      and LD psa data were plotted on the same graph treating both the weighting and
      the size unit of the LD psa data as unknowns. Congruency of the IA and LD plots
      was considered to indicate successful experimental determination of the weighting
      and size unit .The weighting of the resulting LD psa data (so-called volume
      weighted) is shown to be better correlated with IA area-weighted data. The size
      unit of LD psa data is shown to be a function of particle shape. In the case of
      high aspect ratio particles characterized by approximately rectangular faces the
      LD psa data is shown to be a function of multiple particle dimensions being
      related to IA size descriptors through a simple variation of the law of mixtures.
      The results demonstrate that successful correlations between IA and LD psa data
      can be realized in the case of non-spherical particle systems even in the case of
      high aspect ratio particles; however, the inappropriateness of the application of
      the Equivalent Spherical Volume Diameter and the Random Particle Orientation
      assumptions to the interpretation of the LD psa results must first be
      acknowledged. Correlation permits cross validation of IA and LD psa results
      increasing confidence in the accuracy of the data from each orthogonal technique.

PMID- 17025251
TI  - Chemical stabilization of a Delta9-tetrahydrocannabinol prodrug in polymeric
      matrix systems produced by a hot-melt method: role of microenvironment pH.
AB  - This research was conducted in order to fabricate stable polyethylene oxide (PEO)
      based transmucosal systems of a Delta(9)-tetrahydrocannabinol (THC) prodrug, a
      hemisuccinate ester, using a hot-melt method. Since Delta(9)-tetrahydrocannabinol
      hemisuccinate (THC-HS) was heat labile, a series of processing aids were
      evaluated in order to facilitate hot-melt production at lower temperatures,
      thereby reducing THC-HS degradation. The stability of THC-HS was influenced both
      by the processing conditions such as heating time and temperature, and the
      postprocessing storage conditions. The type of formulation additive also affected
      the extent of degradation. In the presence of polyethylene glycol (PEG)-400, the
      percentage of relative degradation of THC-HS to THC was 13.5% and 49.4% at 80
      degrees C and 120 degrees C, respectively. In contrast, incorporation of vitamin
      E succinate (VES) reduced processing degradation to 2.1% and 9.2%, respectively,
      under the same conditions. Severe degradation of THC-HS was observed during
      storage, even under freezing conditions (-18 degrees C). A VES-Noveon AA-1
      combination was observed to best stabilize the prodrug systems both during
      processing and postprocessing. Stabilization of THC-HS was achieved in these
      polyethylene oxide matrices at 4 degrees C, with almost 90% of theoretical drug
      remaining for up to 8 months. Investigation of the pH effect revealed that the pH
      of the microenvironment in these polymeric systems could be modulated to
      significantly improve the stability of THC-HS, degradation being the least in a
      relatively acidic medium.

PMID- 17025252
TI  - In vitro and in vivo evaluation of single-unit commercial conventional tablet and
      sustained-release capsules compared with multiple-unit polystyrene microparticle
      dosage forms of Ibuprofen.
AB  - The major aims of the present study were (1) to select a multiple-unit
      formulation that matched the in vitro dissolution profile of single-unit
      sustained-release commercial capsules, (2) to compare the sustaining/controlling
      efficacy of the selected multiple-unit formulation with that of the single-unit
      commercial conventional tablet and sustained-release capsules, and (3) to
      determine whether an in vitro-in vivo correlation exists for single- and multiple
      unit formulations. Ibuprofen (20%-60% wt/wt)-loaded multiple-unit polystyrene
      microparticles were prepared by an emulsion-solvent evaporation method from an
      aqueous system. The in vitro release profiles obtained in phosphate buffer of pH
      6.8 for drug-loaded polystyrene microparticles and for commercial sustained
      release capsules (Fenlong-SR, 400 mg) were compared. Since the microparticles
      with 30% ibuprofen load showed a release profile comparable to that of the
      Fenlong-SR release profile, the microparticles with this drug load were
      considered to be the optimized/selected formulation and, therefore, were
      subjected to stability study and in vivo study in human volunteers. A single-dose
      oral bioavailability study revealed significant differences in C(max), T(max),
      t(1/2a), t(1/2e), K(a), K(e), and AUC between the conventional tablet and
      optimized or Fenlong-SR capsule dosage forms. However, all the parameters, with
      the exception of K(a) along with relative bioavailability (F) and retard quotient
      (R(Delta)), obtained from the optimized ibuprofen-loaded microparticles were
      lower than that obtained from the commercial Fenlong-SR formulation. Furthermore,
      linear relationship obtained between the percentages dissolved and absorbed
      suggests a means to predict in vivo absorption by measuring in vitro dissolution.

PMID- 17025253
TI  - Influence of long-term stability conditions on microbicidal nucleoside prodrug
      (WHI-07)-loaded gel-microemulsion.
AB  - The objective of this study was to evaluate the long-term stability of the
      antiretroviral spermicide WHI-07 (5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine
      5'-(p-bromophenyl)-methoxyalaninyl phosphate) in a polymer-based microemulsion.
      The recovery and stability of WHI-07 in gel-microemulsion was examined by a
      validated high-performance liquid chromatography (HPLC) method. The stability was
      examined over a period of 24 weeks at 3 controlled temperatures (4 degrees C, 25
      degrees C, and 40 degrees C). The recovery of the prodrug from 0.5% to 2.0% WHI
      07-loaded gel-microemulsion was 99.8%. HPLC analysis revealed that a 2% WHI-07
      loaded gel-microemulsion stored at room temperature and cold temperatures for 24
      weeks retained >90% of the prodrug, whereas those stored at 40 degrees C
      maintained 90% of initial WHI-07 for at least 10 weeks. The observed stability of
      WHI-07 in gel-microemulsion is of great importance for its widespread utility in
      various climatological conditions.

PMID- 17025254
TI  - Cross-linked guar gum microspheres: a viable approach for improved delivery of
      anticancer drugs for the treatment of colorectal cancer.
AB  - In the present work, guar gum microspheres containing methotrexate (MTX) were
      prepared and characterized for local release of drug in the colon, which is a
      prerequisite for the effective treatment of colorectal cancer. Guar gum
      microspheres were prepared by the emulsification method using glutaraldehyde as a
      cross-linking agent. Surface morphological characteristics were investigated
      using scanning electron microscopy. Particle size, shape, and surface morphology
      were significantly affected by guar gum concentration, glutaraldehyde
      concentration, emulsifier concentration (Span 80), stirring rate, stirring time,
      and operating temperature. MTX-loaded microspheres demonstrated high entrapment
      efficiency (75.7%). The in vitro drug release was investigated using a US
      Pharmacopeia paddle type (type II) dissolution rate test apparatus in different
      media (phosphate-buffered saline [PBS], gastrointestinal fluid of different pH,
      and rat cecal content release medium), which was found to be affected by a change
      to the guar gum concentration and glutaraldehyde concentration. The drug release
      in PBS (pH 7.4) and simulated gastric fluids followed a similar pattern and had a
      similar release rate, while a significant increase in percent cumulative drug
      release (91.0%) was observed in the medium containing rat cecal content. In in
      vivo studies, guar gum microspheres delivered most of their drug load (79.0%) to
      the colon, whereas plain drug suspensions could deliver only 23% of their total
      dose to the target site. Guar gum microspheres showed adequate potential in
      achieving local release of drug in in vitro release studies, and this finding was
      further endorsed with in vivo studies.

PMID- 17025255
TI  - Evaluation of powder and tableting properties of chitosan.
AB  - The aim of this study was to analyze the process of tablet formation and the
      properties of the resulting tablets for 3 N-deacetylated chitosans, with a degree
      of deacetylation of 80%, 85%, or 90%. Material properties, such as water content,
      particle size and morphology, glass transition temperature, and molecular weight
      were studied. The process of tablet formation was analyzed by 3-D modeling,
      Heckel analysis, the pressure time function, and energy calculations in
      combination with elastic recovery dependent on maximum relative density and time.
      The crushing force and the morphology of the final tablets were analyzed.
      Chitosans sorb twice as much water as microcrystalline cellulose (MCC), the
      particle size is comparable to Avicel PH 200, a special type of MCC, the
      particles look like shells, and the edges are bent. Molecular weight ranges from
      80,000 to 210,000 kDa, the glass transition temperature (Tg) was not dependent on
      molecular weight. The chitosans deform ductilely as MCC; however, plastic
      deformation with regard to time and also pressure plasticity are higher than for
      MCC, especially for Chit 85, which has the lowest crystallinity and molecular
      weight. At high densification, fast elastic decompression is higher. 3-D modeling
      allowed the most precise analysis. Elastic recovery after tableting is higher
      than for MCC tablets and continues for some time after tableting. The crushing
      force of the resulting tablets is high owing to a reversible exceeding of Tg in
      the amorphous parts of the material. However, the crushing force is lower
      compared with MCC, since the crystallinity and the Tg of the chitosans are higher
      than for MCC. In summation, chitosans show plastic deformation during compression
      combined with high elasticity after tableting. Highly mechanically stable tablets
      result.

PMID- 17025256
TI  - Development of tetracycline-serratiopeptidase-containing periodontal gel:
      formulation and preliminary clinical study.
AB  - The purpose of this research was to reduce the polymer concentration and to
      obtain reasonable viscosity at a lower concentration of pluronic by the addition
      of a viscosity modifier. A 20% wt/wt pluronic gel was prepared on a weight basis
      using the cold method. The effect of the amount of tetracycline and Aerosil on
      gel properties was studied. The gel was evaluated using different parameters:
      polarizing microscopy, gelation, gel melting, bioadhesivity, viscosity, drug
      release, and stability of enzyme. An in vivo study was performed to evaluate the
      clinical efficiency of the liquid crystalline gel. Addition of Aerosil to the gel
      favored hexagonal phase formation. Viscosity and bioadhesivity increased with an
      increase in the concentration of Aerosil. Release of tetracycline was sustained
      as the concentration of Aerosil increased. Various clinical parameters confirmed
      the acceptability and efficiency of this gel system.

PMID- 17025257
TI  - Design and development of microemulsion drug delivery system of acyclovir for
      improvement of oral bioavailability.
AB  - The main purpose of this work was to develop an oral microemulsion formulation
      for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion
      formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was
      developed for oral delivery of acyclovir. Phase behavior and solubilization
      capacity of the microemulsion system were characterized, and in vivo oral
      absorption of acyclovir from the microemulsion was investigated in rats. A single
      isotropic region, which was considered to be a bicontinuous microemulsion, was
      found in the pseudoternary phase diagrams developed at various Labrasol:Plurol
      Oleique:Labrafac ratios. With the increase of Labrasol concentration, the
      microemulsion region area and the amount of water and Labrafac solubilized into
      the microemulsion system increased; however, the increase of Plurol Oleique
      percentage produced opposite effects. The microemulsion system was also
      investigated in terms of other characteristics, such as interfacial tension,
      viscosity, pH, refractive index, diffusion, and bioavailability. Acyclovir, a
      poorly soluble drug, displayed high solubility in a microemulsion formulation
      using Labrafac (10%), Labrasol (32%), Plurol Oleique (8%), and water (50%). The
      in vitro intraduodenal diffusion and in vivo study revealed an increase of
      bioavailability (12.78 times) after oral administration of the microemulsion
      formulation as compared with the commercially available tablets.

PMID- 17025258
TI  - Once-daily tablet formulation and in vitro release evaluation of cefpodoxime
      using hydroxypropyl methylcellulose: a technical note.

PMID- 17025259
TI  - Influence of hydrophilic polymers on celecoxib complexation with hydroxypropyl
      beta-cyclodextrin.
AB  - Complexation of celecoxib with hydroxypropyl beta-cyclodextrin (HPbetaCD) in the
      presence and absence of 3 hydrophilic polymers-polyvinyl pyrrolidone (PVP),
      hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG)-was
      investigated with an objective of evaluating the effect of hydrophilic polymers
      on the complexation and solubilizing efficiencies of HPbetaCD and on the
      dissolution rate of celecoxib from the HPbetaCD complexes. The phase solubility
      studies indicated the formation of celecoxib-HPbetaCD inclusion complexes at a
      1:1M ratio in solution in both the presence and the absence of hydrophilic
      polymers. The complexes formed were quite stable. Addition of hydrophilic
      polymers markedly enhanced the complexation and solubilizing efficiencies of
      HPbetaCD. Solid inclusion complexes of celecoxib-HPbetaCD were prepared in 1:1
      and 1:2 ratios by the kneading method, with and without the addition of
      hydrophilic polymers. The solubility and dissolution rate of celecoxib were
      significantly improved by complexation with HPbetaCD. The celecoxib-HPbetaCD
      (1:2) inclusion complex yielded a 36.57-fold increase in the dissolution rate of
      celecoxib. The addition of hydrophilic polymers also markedly enhanced the
      dissolution rate of celecoxib from HPbetaCD complexes: a 72.60-, 61.25-, and
      39.15-fold increase was observed with PVP, HPMC, and PEG, respectively.
      Differential scanning calorimetry and X-ray diffractometry indicated stronger
      drug amorphization and entrapment in HPbetaCD because of the combined action of
      HPbetaCD and the hydrophilic polymers.

PMID- 17025260
TI  - Pharmacokinetics and bioavailability of the isoflavone biochanin A in rats.
AB  - Biochanin A (BCA) is a dietary isoflavone present in legumes, most notably red
      clover, and in many herbal dietary supplements. BCA has been reported to have
      chemopreventive properties and is metabolized to the isoflavone genistein (GEN),
      BCA conjugates, and GEN conjugates. The metabolites may contribute to the
      chemopreventive effects of BCA. The absorption, metabolism, and disposition of
      BCA have not been determined in rats. Our objective was to evaluate the
      pharmacokinetics and metabolism of BCA in rats. Male Sprague-Dawley rats were
      administered BCA by intravenous injection (1 and 5 mg/kg), by intraperitoneal
      injection (5 and 50 mg/kg), and orally (5 and 50 mg/kg). Plasma and bile samples
      were enzymatically hydrolyzed in vitro to determine conjugate concentrations for
      BCA and GEN. Equilibrium dialysis was used to determine protein binding. The BCA
      and GEN concentrations in plasma, urine, and bile were determined by liquid
      chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic
      parameters of BCA were analyzed by noncompartmental analysis. Significant levels
      of BCA conjugates and GEN conjugates were detected in plasma and bile. Both BCA
      and GEN were found to have a high clearance and a large apparent volume of
      distribution; the bioavailability of both was poor (<4%). Reentry peaks were
      evident after oral administration of both BCA and GEN, suggesting enterohepatic
      cycling. The free fraction of BCA in rat plasma was 1.5%. A 2-compartment model
      that included both linear and nonlinear clearance terms and enterohepatic
      recirculation best described the plasma data. This represents the first
      evaluation of the dose-dependent pharmacokinetics and metabolism of BCA in rats.

PMID- 17025261
TI  - Multiple molecular targets in cancer chemoprevention by curcumin.
AB  - Carcinogenesis encompasses 3 closely associated stages: initiation, progression,
      and promotion. Phytochemicals are nonnutritive components of plants that are
      currently being studied in chemoprevention of various diseases for their
      pleiotropic effects and nontoxicity. Cancer chemoprevention involves the use of
      either natural or synthetic chemicals to prevent the initiation, promotion, or
      progression of cancer. Curcumin is the active constituent of turmeric, which is
      widely used as a spice in Indian cooking. It has been shown to possess anti
      inflammatory, antioxidant, and antitumor properties. Curcumin has also been shown
      to be beneficial in all 3 stages of carcinogenesis. Much of its beneficial effect
      is found to be due to its inhibition of the transcription factor nuclear factor
      kappa B (NF-kappaB) and subsequent inhibition of proinflammatory pathways. This
      review summarizes the inhibition of NF-kappaB by curcumin and describes the
      recently identified molecular targets of curcumin. It is hoped that continued
      research will lead to development of curcumin as an anticancer agent.

PMID- 17025262
TI  - New paradigms and tools in drug design for pain and addiction.
AB  - New modalities providing safe and effective treatment of pain, especially
      prolonged pathological pain, have not appeared despite much effort. In this mini
      review/overview we suggest that new paradigms of drug design are required to
      counter the underlying changes that occur in the nervous system that may elicit
      chronic pain states. We illustrate this approach with the example of designing,
      in a single ligand, molecules that have agonist activity at mu and delta opioid
      receptors and antagonist activities at cholecystokinin (CCK) receptors. Our
      findings thus far provide evidence in support of this new approach to drug
      design. We also report on a new biophysical method, plasmon waveguide resonance
      (PWR) spectroscopy, which can provide new insights into information transduction
      in G-protein coupled receptors (GPCRs) as illustrated by the delta opioid
      receptor.

PMID- 17025263
TI  - Targeted lipidomics: discovery of new fatty acyl amides.
AB  - The discovery of endogenous fatty acyl amides such as N-arachidonoyl ethanolamide
      (anandamide), N-oleoyl ethanolamide (OEA), and N-arachidonoyl dopamine (NADA) as
      important signaling molecules in the central and peripheral nervous system has
      led us to pursue other unidentified signaling molecules. Until recently,
      technical challenges, particularly those associated with lipid purification and
      chemical analysis, have hindered the identification of low abundance signaling
      lipids. Improvements in chromatography and mass spectrometry (MS) such as
      miniaturization of high-performance liquid chromatography components,
      hybridization of multistage mass spectrometers and time-of-flight technology, the
      development of electrospray ionization (ESI) and of information-dependent
      acquisition, now permit rapid identification of novel, low abundance, signaling
      lipids.

PMID- 17025265
TI  - Agmatine: biological role and therapeutic potentials in morphine analgesia and
      dependence.
AB  - Agmatine is an amine that is formed by decarboxylation of L-arginine by the
      enzyme arginine decarboxylase (ADC) and hydrolyzed by the enzyme agmatinase to
      putrescine. Agmatine binds to several target receptors in the brain and has been
      proposed as a novel neuromodulator. In animal studies, agmatine potentiated
      morphine analgesia and reduced dependence/withdrawal. While the exact mechanism
      is not clear, the interactions with N-methyl-D-aspartate (NMDA) receptors, alpha2
      adrenergic receptors, and intracellular cyclic adenosine monophosphate (cAMP)
      signaling have been proposed as possible targets. Like other monoamine
      transmitter molecules, agmatine is rapidly metabolized in the periphery and has
      poor penetration into the brain, which limits the use of agmatine itself as a
      therapeutic agent. However, the development of agmatinase inhibitors will offer a
      useful method to increase endogenous agmatine in the brain as a possible
      therapeutic approach to potentiate morphine analgesia and reduce
      dependence/withdrawal. This review provides a succinct discussion of the
      biological role/therapeutic potential of agmatine during morphine exposure/pain
      modulation, with an extensive amount of literature cited for further details.

PMID- 17025264
TI  - Issues related to targeted delivery of proteins and peptides.
AB  - While modern genomic and proteomic technology enables rapid screening of novel
      proteins and peptides as potential drug candidates, design of delivery systems
      for these biologics remains challenging especially to achieve site-specific
      pharmacological actions. This article discusses the issues associated with
      targeted delivery of protein and peptide drugs at physiochemical, physiological,
      and intracellular levels with a special focus on cancer therapy.

PMID- 17025266
TI  - The kinetics of thiol-mediated decomposition of S-nitrosothiols.
AB  - The reaction of sulfhydryl (SH)-containing molecules (thiols) with S
      nitrosothiols (RSNO) has been shown to be of biological importance. Biologically
      or therapeutically relevant thiols generally have a pKa value ranging from 8 to
      10 for the SH group. In addition, some of these thiols contain a carboxyl group
      and are acidic, which should be considered in studying the reaction between RSNO
      and thiols. In the present study, the kinetics of thiol-mediated decomposition of
      RSNO was investigated in a commonly used phosphate buffer, phosphate buffered
      saline (PBS; containing 6.9 mM phosphates; buffer capacity = 3.8 mM/pH). The
      thiols studied can be divided into 2 groups, depending on their pH perturbation
      capacity. The kinetics was studied using a wide range of thiol concentrations
      (ie, from 0.1 to 10 mM). A high-performance liquid chromatography (HPLC) method
      was used to determine RSNO concentrations. The results showed that the acidic
      thiols, including glutathione, captopril, N-acetylcysteine, and tiopronin,
      stimulated RSNO decomposition at low millimolar concentrations up to 2 mM. The
      stimulatory effect, however, became attenuated at concentrations higher than 2 mM
      in PBS. Increasing the concentration of acidic thiols caused a decrease in
      solution pH, which was attributable to the inhibitory effect at high thiol
      concentrations. The effect of thiols on the pH of reaction solution, and the
      resulting bell-shaped rate profiles, can be predicted by a quantitative analysis,
      from which a comparison of the intrinsic reactivity toward RSNO, among 8 thiols,
      was possible. The intrinsic reactivity in general followed the Bronsted relation.

PMID- 17025267
TI  - Rapid in vivo oral screening in rats: reliability, acceptance criteria, and
      filtering efficiency.
AB  - The reliability and acceptance criteria of rapid oral exposure screening were
      evaluated by pharmacokinetic simulations and by comparing oral exposure of 100
      proprietary compounds from 15 therapeutic programs obtained at different times by
      cassette accelerated rapid rat screen (CARRS) and conventional pharmacokinetic
      (full-PK) procedures. Once acceptance criteria were established, the filtering
      efficiency (discard rate) was assessed with a larger data set of 5289 compounds
      tested by CARRS only. These evaluations indicated that area under the
      concentration-time curve during the first 6 hours (AUC(6h)) captured >50% of
      AUC(infinity) for most (71%) of the compounds and AUC(6h) from CARRS is
      comparable to AUC(6h) from full-PK in categorizing oral exposure as low,
      moderate, or high; therefore, the truncated AUC(6h) derived from pooled plasma
      samples is suitable for oral exposure screening. The CARRS profiles did not
      provide reliable half-life estimates; however, compounds with substantial AUC
      beyond 6 hours can be identified when (C(6h)/Cmax x 100%) exceeds 80%. Of
      interest, both the observed data and the simulated data indicated that AUC(6h)
      can be estimated using a single time point plasma concentration at 3 hours. The
      relationship between the maximum bioavailability and AUC(infinity) over a range
      of clearance values was simulated. A threshold AUC (500 h*ng/mL) at the routine
      screening dose of 10 mg/kg was established below which a compound can be
      discarded. Examination of screening results for 5289 compounds evaluated over the
      last few years in our laboratory indicated that CARRS had a filtering efficiency
      of 50%, suggesting that this criterion provides a useful decision gate to avoid
      wasting the drug discovery resources on nonviable candidates.

PMID- 17025268
TI  - Effects of protein aggregates: an immunologic perspective.
AB  - The capacity of protein aggregates to enhance immune responses to the monomeric
      form of the protein has been known for over a half-century. Despite the clear
      connection between protein aggregates and antibody mediated adverse events in
      treatment with early therapeutic protein products such as intravenous immune
      globulin (IVIG) and human growth hormone, surprisingly little is known about the
      nature of the aggregate species responsible for such effects. This review focuses
      on a framework for understanding how aggregate species potentially interact with
      the immune system to enhance immune responses, garnered from basic immunologic
      research. Thus, protein antigens presented in a highly arrayed structure, such as
      might be found in large nondenatured aggregate species, are highly potent in
      inducing antibody responses even in the absence of T-cell help. Their potency may
      relate to the ability of multivalent protein species to extensively cross-link B
      cell receptor, which (1) activates B cells via Bt kinases to proliferate, and (2)
      targets protein to class II major histocompatibility complex (MHC)-loading
      compartments, efficiently eliciting T-cell help for antibody responses. The
      review further focuses on protein aggregates as they affect an immunogenicity
      risk assessment, the use of animal models and studies in uncovering effects of
      protein aggregates, and changes in product manufacture and packaging that may
      affect generation of protein aggregates.

PMID- 17025269
TI  - MicroPET investigation of chronic long-term neurotoxicity from heavy ion
      irradiation.
AB  - Positron emission tomography (PET) permits imaging of the regional
      biodistribution and pharmacokinetics of compounds labeled with short-lived
      positron-emitting isotopes. It has enabled evaluation of neurochemical systems in
      the living human brain, including effects of toxic substances. MicroPET devices
      allow studies of the rat brain with a spatial resolution of approximately 2 mm.
      This is much poorer resolution than obtained using ex vivo autoradiography.
      However, animals need not be euthanized before imaging, so repeat studies are
      possible. This in principle allows the effects of toxic insults to be followed
      over the lifetime of an individual animal. We used microPET to evaluate brain
      metabolic effects of irradiation with high-energy heavy ions (HZE radiation), a
      component of the space radiation environment, on regional glucose metabolism. A
      significant fraction of neurons would be traversed by these densely ionizing
      particles during a Mars mission, and there is a need to estimate human
      neurological risks of prolonged voyages beyond the geomagnetosphere. Rats were
      irradiated with 56Fe (600 MeV/n) ions at doses up to 240 cGy. At 9 months post
      irradiation we did not detect alterations in regional accumulation of the glucose
      analog [18F]2-deoxy-2-fluoro-D-glucose. This may indicate that damage to the
      brain from HZE particles is less severe than feared. However, because radiation
      induced alterations in some behaviors have been documented, it may reflect
      insensitivity of baseline cerebral glucose metabolism to HZE radiation. These
      studies will facilitate design of future studies of chronic, long-term exposure
      to both therapeutic and abused drugs using microPET.

PMID- 17025270
TI  - Searching for polymorphisms that affect gene expression and mRNA processing:
      example ABCB1 (MDR1).
AB  - Cis-acting genetic variations can affect the amount and structure of
      mRNA/protein. Genomic surveys indicate that polymorphisms affecting transcription
      and mRNA processing, including splicing and turnover, may account for the main
      share of genetic factors in human phenotypic variability; however, most of these
      polymorphisms remain yet to be discovered. We use allelic expression imbalance
      (AEI) as a quantitative phenotype in the search for functional cis-acting
      polymorphisms in many genes, including ABCB1 (multidrug resistance 1 gene, MDR1,
      Pgp). Previous studies have shown that ABCB1 activity correlates with a
      synonymous polymorphism, C3435T; however, the functional polymorphism and
      molecular mechanism underlying this clinical association remained unknown.
      Analysis of allele-specific expression in liver autopsy samples and in vitro
      expression experiments showed that C3435T represents a main functional
      polymorphism, accounting for 1.5- to 2-fold changes in mRNA levels. The mechanism
      appears to involve increased mRNA turnover, probably as a result of different
      folding structures calculated for mRNA with the Mfold program. Other examples of
      the successful application of AEI analysis for studying functional polymorphism
      include 5-HTT (serotonin transporter, SLC6A4) and OPRM1 (mu opioid receptor). AEI
      is therefore a powerful approach for detecting cis-acting polymorphisms affecting
      gene expression and mRNA processing.

PMID- 17025271
TI  - Mitochondria-targeted peptide antioxidants: novel neuroprotective agents.
AB  - Increasing evidence suggests that mitochondrial dysfunction and oxidative stress
      play a crucial role in the majority of neurodegenerative diseases. Mitochondria
      are a major source of intracellular reactive oxygen species (ROS) and are
      particularly vulnerable to oxidative stress. Oxidative damage to mitochondria has
      been shown to impair mitochondrial function and lead to cell death via apoptosis
      and necrosis. Because dysfunctional mitochondria will produce more ROS, a feed
      forward loop is set up whereby ROS-mediated oxidative damage to mitochondria
      favors more ROS generation, resulting in a vicious cycle. It is now appreciated
      that reduction of mitochondrial oxidative stress may prevent or slow down the
      progression of these neurodegenerative disorders. However, if mitochondria are
      the major source of intracellular ROS and mitochondria are most vulnerable to
      oxidative damage, then it would be ideal to deliver the antioxidant therapy to
      mitochondria. This review will summarize the development of a novel class of
      mitochondria-targeted antioxidants that can protect mitochondria against
      oxidative stress and prevent neuronal cell death in animal models of stroke,
      Parkinson's disease, and amyotrophic lateral sclerosis.

PMID- 17025273
TI  - Development and evaluation of a population pharmacokinetic-pharmacodynamic model
      of darbepoetin alfa in patients with nonmyeloid malignancies undergoing
      multicycle chemotherapy.
AB  - Anemia is frequently observed in patients undergoing chemotherapy. Administration
      of darbepoetin alfa, a recombinant erythropoiesis-stimulating agent that has
      longer residence time than endogenous erythropoietin, to patients with
      chemotherapy-induced anemia (CIA) increases mean hemoglobin concentration,
      reduces risk of red blood cell transfusions, and improves patient-reported
      outcomes. A pharmacokinetic/pharmacodynamic (PkPd) model was developed using data
      from patients with nonmyeloid malignancies and CIA who were receiving darbepoetin
      alfa. A 2-compartment Pk model with linear elimination described the Pk data
      obtained in 140 CIA patients after intravenous and subcutaneous (s.c.) doses of
      2.25 microg/kg every week and s.c. doses of 6.75 microg/kg every 3 weeks. The
      population typical values of key Pk parameters were clearance, 2010 mL/day;
      steady-state volume of distribution, 3390 mL; and bioavailability, 44.3%. A
      modified indirect response model, wherein serum concentrations stimulated the
      production of hemoglobin through an Emax-type equation, described the hemoglobin
      levels after s.c. doses of 0.5 microg/kg every week to 15 microg/kg every 3 weeks
      in 573 CIA patients. The estimated incremental maximum stimulation of hemoglobin
      production was 43.7% and darbepoetin alfa serum concentration at half-maximal
      stimulation was 3.68 ng/mL. The impact of covariates (body weight and platinum
      containing chemotherapy) on the PkPd response was evaluated based on point and
      interval estimates of parameters, rather than through stepwise hypothesis
      testing. The final PkPd model adequately predicted hemoglobin response in a test
      data set, thereby confirming the predictive capability of the model. Based on
      simulations, it was not possible to categorize the influence of any covariate as
      clinically important.

PMID- 17025274
TI  - Is any measurement method optimal for all aggregate sizes and types?
AB  - Protein-based pharmaceuticals exhibit a wide range of aggregation phenomena,
      making it virtually impossible to find any one analytical method that works well
      in all cases. Aggregate sizes cover a range from small oligomers to visible
      "snow" and precipitates, and generally only the smaller species are reversible.
      It is less widely recognized that aggregates also exhibit a broad spectrum of
      lifetimes, and the lifetime has important consequences for detection methods. The
      fact that the measurement itself may destroy or create aggregates poses a major
      analytical challenge and is a key determinant for method selection. Several
      examples of some interesting aggregation phenomena and the analytical approaches
      we have used are presented. In one case, an "aggregate" seen by SEC in stressed
      samples was shown to actually be a partially denatured monomer using both size
      exclusion chromatography with online multiangle laser light scattering (SEC
      MALLS) and sedimentation velocity. In a second case, freeze/thaw stress generates
      transient, metastable oligomers that are extremely sticky and difficult to
      measure by SEC. By using sedimentation velocity as the "gold standard" a much
      improved SEC method was developed and used to investigate the temperature
      dependent dissociation of these oligomers. For problems with visible
      particulates, dynamic light scattering has been effective, in our hands, at
      detecting the precursors to the large, visible particles and tracking the source
      of stress or damage to particular manufacturing steps.

PMID- 17025272
TI  - Immunotoxins for targeted cancer therapy.
AB  - Immunotoxins are proteins that contain a toxin along with an antibody or growth
      factor that binds specifically to target cells. Nearly all protein toxins work by
      enzymatically inhibiting protein synthesis. For the immunotoxin to work, it must
      bind to and be internalized by the target cells, and the enzymatic fragment of
      the toxin must translocate to the cytosol. Once in the cytosol, 1 molecule is
      capable of killing a cell, making immunotoxins some of the most potent killing
      agents. Various plant and bacterial toxins have been genetically fused or
      chemically conjugated to ligands that bind to cancer cells. Among the most active
      clinically are those that bind to hematologic tumors. At present, only 1 agent,
      which contains human interleukin-2 and truncated diphtheria toxin, is approved
      for use in cutaneous T-cell lymphoma. Another, containing an anti-CD22 Fv and
      truncated Pseudomonas exotoxin, has induced complete remissions in a high
      proportion of cases of hairy-cell leukemia. Refinement of existing immunotoxins
      and development of new immunotoxins are underway to improve the treatment of
      cancer.

PMID- 17025275
TI  - Protein aggregation and bioprocessing.
AB  - Protein aggregation is a common issue encountered during manufacture of
      biotherapeutics. It is possible to influence the amount of aggregate produced
      during the cell culture and purification process by carefully controlling the
      environment (eg, media components) and implementing appropriate strategies to
      minimize the extent of aggregation. Steps to remove aggregates have been
      successfully used at a manufacturing scale. Care should be taken when developing
      a process to monitor the compatibility of the equipment and process with the
      protein to ensure that potential aggregation is minimized.

PMID- 17025276
TI  - A critical review of analytical ultracentrifugation and field flow fractionation
      methods for measuring protein aggregation.
AB  - Analytical ultracentrifugation (AUC) and field flow fractionation (FFF) are 2
      important biophysical methods for measuring protein aggregates. Both methods can
      separate protein monomer from its aggregate forms under a broad range of solution
      conditions. Recent advances in instrumentation and data analysis, particularly in
      the field of analytical ultracentrifugation technology, have significantly
      improved the capability and sensitivity of these biophysical methods for
      detecting protein aggregates. These advances have resulted in an increased use of
      these methods in the biopharmaceutical industry for characterization of
      therapeutic proteins. However, despite their many advantages over conventional
      methods, the difficulty in the use of the instrumentation and the complexity of
      data analysis process, have often hampered the widespread use and proper
      interpretation of data. This article reviews the recent progress in both
      technologies, and a few case studies are also presented to discuss their
      advantages and limitations.

PMID- 17025277
TI  - Role of analytical ultracentrifugation in assessing the aggregation of protein
      biopharmaceuticals.
AB  - In developing and manufacturing protein biopharmaceuticals, aggregation is a
      parameter that needs careful monitoring to ensure the quality and consistency of
      the final biopharmaceutical drug product. The analytical method of choice used to
      perform this task is size-exclusion chromatography (SEC). However, it is becoming
      more and more apparent that considerable care is required in assessing the
      accuracy of SEC data. One old analytical tool that is now reappearing to help in
      this assessment is analytical ultracentrifugation (AUC). Developments in AUC
      hardware and, more importantly, recent developments in AUC data analysis computer
      programs have converged to provide this old biophysical tool with the ability to
      extract very high resolution size information about the molecules in a given
      sample from a simple sedimentation velocity experiment. In addition, AUC allows
      sample testing to be conducted in the exact or nearly exact liquid formulation or
      reconstituted liquid formulation of the biopharmaceutical in the vial, with
      minimal surface area contact with extraneous materials. As a result, AUC analysis
      can provide detailed information on the aggregation of a biopharmaceutical, while
      avoiding many of the major problems that can plague SEC, thus allowing AUC to be
      used as an orthogonal method to verify SEC aggregation information and the
      associating properties of biopharmaceuticals.

PMID- 17025279
TI  - Amphipathic helices from aromatic amino acid oligomers.
AB  - Synthetic helical foldamers are of significant interest for mimicking the
      conformations of naturally occurring molecules while at the same time introducing
      new structures and properties. In particular, oligoamides of aromatic amino acids
      are attractive targets, as their folding is highly predictable and stable. Here
      the design and synthesis of new amphipathic helical oligoamides based on
      quinoline-derived amino acids having either hydrophobic or cationic side chains
      are described. Their structures were characterized in the solid state by single
      crystal X-ray diffraction and in solution by NMR. Results of these studies
      suggest that an oligomer as short as a pentamer folds into a stable helical
      conformation in protic solvents, including MeOH and H(2)O. The introduction of
      polar proteinogenic side chains to these foldamers, as described here for the
      first time, promises to provide possibilities for the biological applications of
      these molecules. In particular, amphipathic helices are versatile targets to
      explore due to their importance in a variety of biological processes, and the
      unique structure and properties of the quinoline-derived oligoamides may allow
      new structure-activity relationships to be developed.

PMID- 17025280
TI  - Dications of 3-phenylindenylidenefluorenes: evaluation of antiaromaticity of
      indenyl and fluorenyl cations by magnetic measures.
AB  - Dications of p-substituted 3-phenylindenylidenefluorenes were prepared to examine
      the response of the resulting indenyl and fluorenyl cationic systems to magnetic
      measures of antiaromaticity. All measures, (1)H NMR shifts, nucleus independent
      chemical shifts (NICS(1)(zz)), and magnetic susceptibility exaltation, Lambda,
      supported the antiaromaticity of the dications 3a-f2+. The 1H NMR shifts and
      NICS(1)(zz) showed that the indenyl ring system was less antiaromatic than the
      fluorenyl ring system, contrary to the antiaromaticity of indenyl monocations
      compared to fluorenyl monocations. The presence of a phenyl substituent in the 3
      position was able to stabilize the indenylidene cation through resonance,
      decreasing its antiaromaticity, but even in the absence of the 3-phenyl
      substituent, the indenyl system of indenylidenefluorene dications was less
      antiaromatic than the fluorenyl system. The decreased antiaromaticity of the 3
      phenylindenylidenefluorene dications over the unsubstituted indenylidenefluorene
      dication was supported by (anti)aromatic (de)stabilization energy calculations,
      ASE.

PMID- 17025281
TI  - Pteratides I-IV, new cytotoxic cyclodepsipeptides from the Malaysian
      basidiomycete Pterula sp.
AB  - Four new cyclodepsipeptides, pteratides I-IV (1-4), have been isolated from the
      extract of a Pterula species collected from a Malaysian tropical forest.
      Homonuclear and heteronuclear 2D NMR techniques as well as MS fragmentation
      experiments, in combination with methanolysis, determined the gross structures of
      the peptides and showed that pteratides I and II each contained the
      nonproteinogenic amino acid 4-methylproline. The absolute configurations of the
      amino acids in pteratides I-IV were established using Marfey's method. Pteratides
      I and II are each potently cytotoxic against the P388 murine leukemia cell line
      (IC50 values of 41 and 40 nM, respectively). Pteratides III and IV show weaker,
      but still notable, activity with IC50 values of 7.4 and 2.9 microM, respectively.

PMID- 17025282
TI  - Abc amino acids: design, synthesis, and properties of new photoelastic amino
      acids.
AB  - Photoisomerizable amino acids provide a direct avenue to the experimental
      manipulation of bioactive polypeptides, potentially allowing real-time, remote
      control of biological systems and enabling useful applications in
      nanobiotechnology. Herein, we report a new class of photoisomerizable amino acids
      intended to cause pronounced expansion and contraction in the polypeptide
      backbone, i.e., to be photoelastic. These compounds, termed Abc amino acids,
      employ a photoisomerizable azobiphenyl chromophore to control the relative
      disposition of aminomethyl and carboxyl substituents. Molecular modeling of nine
      Abc isomers led to the identification of one with particularly attractive
      properties, including the ability to induce contractions up to 13 A in the
      backbone upon trans --> cis photoisomerization. This isomer, designated mpAbc,
      has substituents at meta and para positions on the inner (azo-linked) and outer
      rings, respectively. An efficient synthesis of Fmoc-protected mpAbc was executed
      in which the biaryl components were formed via Suzuki couplings and the azo
      linkage was formed via amine/nitroso condensation; protected forms of three other
      Abc isomers were prepared similarly. An undecapeptide incorporating mpAbc was
      synthesized by conventional solid-phase methods and displayed characteristic
      azobenzene photochemical behavior with optimal conversion to the cis isomer at
      360 nm and a thermal cis --> trans half-life of 100 min at 80 degrees C.

PMID- 17025278
TI  - Modulation of microglial pro-inflammatory and neurotoxic activity for the
      treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is a debilitating movement disorder resulting from a
      progressive degeneration of the nigrostriatal dopaminergic pathway and depletion
      of neurotransmitter dopamine in the striatum. Molecular cloning studies have
      identified nearly a dozen genes or loci that are associated with small clusters
      of mostly early onset and genetic forms of PD. The etiology of the vast majority
      of PD cases remains unknown, and the precise molecular and biochemical processes
      governing the selective and progressive degeneration of the nigrostriatal
      dopaminergic pathway are poorly understood. Current drug therapies for PD are
      symptomatic and appear to bear little effect on the progressive neurodegenerative
      process. Studies of postmortem PD brains and various cellular and animal models
      of PD in the last 2 decades strongly suggest that the generation of pro
      inflammatory and neurotoxic factors by the resident brain immune cells,
      microglia, plays a prominent role in mediating the progressive neurodegenerative
      process. This review discusses literature supporting the possibility of
      modulating the activity of microglia as a neuroprotective strategy for the
      treatment of PD.

PMID- 17025283
TI  - Homologation method for preparation of substituted pentacenes and naphthacenes.
AB  - Multi-substituted pentacenes, such as 1,2,3,4,6,8,9,10,11,13-decasubstituted
      pentacenes (Type I), 1,2,3,4,6,13-hexasubstituted pentacenes (Type II), 1,2,3,4
      tetrasubstituted pentacenes (Type III), and 2,3-disubstituted pentacenes (Type
      IV), 1,2,3,4,6,11-hexasubstituted naphthacenes (Type V), 1,2,3,4-tetrasubstituted
      naphthacenes (Type VI), and 2,3-disubstituted naphthacenes (Type VII), were
      prepared by a homologation method. The homologation method involved the
      conversion of phthalic acid ester derivatives to two ring extended phthalic acid
      ester derivatives via diynes and metallacyclopentadienes using transition metals,
      such as Zr and Rh. For the formation of pentacenes of Type III and Type IV and
      naphthacenes of Type VII, trimethylsilyl-substituted diynes were used for
      zirconocene-mediated cyclization. Elimination of the trimethylsilyl groups after
      the cyclization afforded nonsubstituted position on pentacenes or naphthacenes.
      Structures of 1,4,6,8,9,10,11,13-octaethyl-2,3-bis(methoxycarbonyl)pentacene (9a)
      and 8,9,10,11-tetraethyl-2,3-bis(methoxycarbonyl)-1,4,6,13-tetrapropylpentacene
      (9b) were determined by X-ray analysis. The structure of 9a had the herringbone
      packing system in the crystal like nonsubstituted pentacene. However, 9b, whose
      substituents at 1,4,6,13-positions were changed from Et to Pr at 1,4,6,13
      positions of 9a, had the face parallel plane system in the crystal.

PMID- 17025284
TI  - One-pot carbanionic synthesis of P1,P2-diglycosyl, P1,P1,P2-triglycosyl, and
      P1,P1,P2,P2-tetraribosyl methylenediphosphonates.
AB  - Novel lithiated carbanions derived from ethyl glycosyl- and diglycosyl
      methylphosphonates were used in a direct and convenient synthesis of P1,P2
      diglycosyl, P1,P1,P2-triglycosyl, and P1,P1,P2,P2-tetraribosyl
      methylenediphosphonates involving a one-pot methylidenediphosphonylation of
      sugars.

PMID- 17025285
TI  - Palladium-mediated functionalization of heteroaromatic cations: comparative study
      on quinolizinium cations.
AB  - An efficient palladium-catalyzed cross-coupling reaction on heteroaromatic
      cations is described. A comparative study of the Stille and Suzuki reactions
      shows that only the Stille reaction is able to produce an efficient C-C bond
      formation between any of the four isomeric bromoquinolizinium bromides and a
      variety of stannanes. In the presence of the catalysts Pd(PPh3)4 or Pd2(dba)3P(o
      Tol)3, vinyl, ethynyl, aryl, and heteroaryl groups are successfully incorporated
      into the quinolizinium system in satisfactory yields under mild reaction
      conditions. This procedure represents a marked improvement on the
      functionalization of this class of heteroaromatic cation.

PMID- 17025286
TI  - The loss of carbon dioxide from activated perbenzoate anions in the gas phase:
      unimolecular rearrangement via epoxidation of the benzene ring.
AB  - The unimolecular reactivities of a range of perbenzoate anions (X-C6H5CO3-),
      including the perbenzoate anion itself (X = H), nitroperbenzoates (X = para-,
      meta-, ortho-NO2), and methoxyperbenzoates (X = para-, meta-OCH3) were
      investigated in the gas phase by electrospray ionization tandem mass
      spectrometry. The collision-induced dissociation mass spectra of these compounds
      reveal product ions consistent with a major loss of carbon dioxide requiring
      unimolecular rearrangement of the perbenzoate anion prior to fragmentation.
      Isotopic labeling of the perbenzoate anion supports rearrangement via an initial
      nucleophilic aromatic substitution at the ortho carbon of the benzene ring, while
      data from substituted perbenzoates indicate that nucleophilic attack at the ipso
      carbon can be induced in the presence of electron-withdrawing moieties at the
      ortho and para positions. Electronic structure calculations carried out at the
      B3LYP/6-311++G(d,p) level of theory reveal two competing reaction pathways for
      decarboxylation of perbenzoate anions via initial nucleophilic substitution at
      the ortho and ipso positions, respectively. Somewhat surprisingly, however, the
      computational data indicate that the reaction proceeds in both instances via
      epoxidation of the benzene ring with decarboxylation resulting--at least
      initially--in the formation of oxepin or benzene oxide anions rather than the
      energetically favored phenoxide anion. As such, this novel rearrangement of
      perbenzoate anions provides an intriguing new pathway for epoxidation of the
      usually inert benzene ring.

PMID- 17025287
TI  - Intramolecular thia-anti-Michael addition of a sulfur anion to enones: a
      regiospecific approach to multisubstituted thiophene derivatives.
AB  - The intramolecular thia-anti-Michael addition starting from readily available
      alpha-alkenoyl-alpha'-carbamoyl ketene-(S,S)-acetals 1 containing a 1,3
      dithiolane moiety was developed. In particular, in the presence of aliphatic
      primary amines, a series of tetrasubstituted thiophene derivatives, 2
      (alkylamino)-5-alkyl-4-hydroxythiophene-3-carboxamides 2, were synthesized via
      tandem fragmentation, substitution, and intramolecular thia-anti-Michael addition
      reactions of 1, where amine played the dual roles of a base and a nucleophile.
      The intramolecular thia-anti-Michael addition, as the key step, proceeded in a
      regiospecific manner and showed a general scope to the beta-substituents of
      enones 1. A possible mechanism for the formation of the multisubstituted
      thiophenes was proposed. By this research, a new and efficient route to various
      tetrasubstituted thiophene derivatives was created.

PMID- 17025288
TI  - A PCT-based, pyrene-armed calix[4]crown fluoroionophore.
AB  - A photoinduced charge transfer (PCT)-based 1,3-alternate calix[4]crown
      fluoroionophore containing two cation recognition sites, a crown ether ring and
      two facing pyreneamide groups, is synthesized. Upon addition of K+, Pb2+, or
      Cu2+, wavelength changes are observed in both the fluorescence and absorption
      spectra, but with different binding modes. With K+, fluorescence emissions of the
      ligand scarcely change, while addition of Pb2+ or Cu2+ produces a remarkable
      change in both the excimer and monomer emissions. The observed data indicate that
      the metal cation is encapsulated in the crown-5 ring for K+ and by the two facing
      amide groups in the latter case, which is verified by a metal ion exchange
      experiment. The wavelength shifts in both fluorescence and absorption spectra
      upon addition of Cu2+ show that, in contrast to Pb2+, Cu2+ interacts with the
      nitrogen atoms of the amide groups, resulting in a PCT mechanism.

PMID- 17025289
TI  - Metal ion sensing novel calix[4]crown fluoroionophore with a two-photon
      absorption property.
AB  - 1,3-Alternate calix[4]arene-based fluorescent chemosensors bearing two-photon
      absorbing chromophores have been synthesized, and their sensing behaviors toward
      metal ions were investigated via absorption band shifts as well as one- and two
      photon fluorescence changes. Free ligands absorb the light at 461 nm and weakly
      emit their fluorescence at 600 nm when excited by UV-vis radiation at 461 nm, but
      no two-photon excited fluorescence is emitted by excitation at 780 nm. Addition
      of an Al(3+) or Pb(2+) ion to a solution of the ligand causes a blue-shifted
      absorption and enhanced fluorescence due to a declined resonance energy transfer
      (RET) upon excitation by one- and two-photon processes. Addition of a Pb(2+) ion
      to a solution of 1.K(+) results in a higher fluorescence intensity than the
      original 1.Pb(2+) complex regardless of one- or two-photon excitation, due to the
      allosteric effect induced by the complexation of K(+) with a crown loop.

PMID- 17025291
TI  - Abstraction of iodine from aromatic iodides by alkyl radicals: steric and
      electronic effects.
AB  - Abstraction of the iodine atom from aryl iodides by alkyl radicals takes place in
      some cases very efficiently despite the unfavorable difference in bond
      dissociation energies of C-I bonds in alkyl and aryl iodides. The abstraction is
      most efficient in iodobenzenes, ortho-substituted with bulky groups. The ease of
      abstraction can be explained by the release of steric strain during the
      elimination of the iodine atom. The rate of abstraction correlates fairly well
      with the strain energy, calculated by density functional theory (DFT) and Hartree
      Fock (HF) methods as a difference in the total energy of ortho and para isomers.
      However, besides the steric bulk, the presence of some other functional groups in
      an ortho substituent also influences the rate. The stabilization of the
      transition state, resembling a 9-I-2 iodanyl radical, by electron-withdrawing
      groups seems to explain a positive sign of the Hammett rho value in the radical
      abstraction of halogen atoms.

PMID- 17025290
TI  - Efficient solvent-free selective monoalkylation of arylacetonitriles with mono-,
      bis-, and tris-primary alcohols catalyzed by a Cp*Ir complex.
AB  - Our objectives were to develop catalytic atom-economic processes accessing and/or
      incorporating versatile functionality using aryl/heteroaryl acetonitriles as
      substrates. We report essentially solvent-free [Cp*IrCl2]2 catalyzed redox
      neutral processes whereby substituted acetonitriles react with primary alcohols
      to deliver monosubstituted aryl/heteroaryl acetonitriles in excellent yield. We
      further demonstrate that such processes can be achieved by conventional or
      microwave heating and that bis- and tris-primary alcohols are also processed
      efficiently.

PMID- 17025292
TI  - Naphthalene- and anthracene-based aromatic foldamers with iminodicarbonyl
      linkers: their stabilities and application to a chiral photochromic system using
      retro [4 + 4] cycloaddition.
AB  - A circular dichroism (CD) spectral study on chiral aromatic chain imides
      possessing anthracene and naphthalene moieties with bulky N substituents showed
      that their helical chirality based on folding remained for a reasonably long time
      without racemization in solution. Racemization due to conformational
      equilibration occurred very slowly, requiring over 1 week at ambient temperature.
      Their CD spectra both in solution and in the solid state gave similar CD signals,
      suggesting retention of helicity observed in the solid state even after
      dissolving. As an application of this novel chiral folding of aromatic chain
      imides, a chiral photochromic system was investigated based on the photo [4 + 4]
      cycloaddition and its thermal cycloreversion of an anthracene-naphthalene system.
      The foldamer possessing an anthracene moiety in the center connected with two
      naphthalene moieties below and above it by iminodicarbonyl linkers was prepared
      for this purpose. Induced CD was observed for the foldamer with (S)-1-(1
      naphthyl)ethyl substituents at the imide nitrogen atoms. Chiral photochromic
      cycles were monitored by CD spectral measurement.

PMID- 17025293
TI  - Synthesis of 2-alkenyl-3-(alkoxycarbonyl)furans based on Feist-Benary
      cyclocondensation of (2,4-dioxobutylidene)phosphoranes with alpha-haloketones and
      alpha-chloracetaldehyde.
AB  - 3-Acyl-2-alkenylfurans were prepared by "Feist-Benary cyclocondensation" of (2,4
      dioxobutylidene)phosphoranes with chloracetaldehyde and alpha-haloketones and
      subsequent Wittig reactions.

PMID- 17025294
TI  - Photochemistry of 2-alkoxymethyl-5-methylphenacyl chloride and benzoate.
AB  - Irradiation of 2-(alkoxymethyl)-5-methyl-alpha-chloroacetophenones (1a-c) and 2
      (methoxymethyl)-5-methylphenacyl benzoate (1d) in dry, nonnucleophilic solvents
      afforded 3-alkoxy-6-methylindan-1-ones (3a-c) in very high chemical yields. 3
      Methylisobenzofuran-1(3H)-one (2) was, however, isolated as a major photoproduct
      in the presence of trace amounts of water. Quenching experiments and laser flash
      spectroscopy revealed that the indanone derivatives 3 are formed by 1,5-hydrogen
      migration from the lowest triplet excited state of the acetophenones 1 and
      cyclization of the resulting photoenols. In contrast, production of the lactone 2
      in wet solvents was found to result from two consecutive photochemical
      transformations. The photoenols produced by photolysis of 1a-c add water as a
      nucleophile to form 2-acetyl-4-methylbenzaldehyde (4), which is further converted
      to 2 via a second, singlet state photoenolization process. Exhaustive photolysis
      of 1a in methanol produced the acetal 2-(dimethoxymethyl)-5-methylacetophenone
      (7a) as the exclusive product. The remarkable selectivity of these photoreactions
      may well be useful in synthetic organic chemistry.

PMID- 17025295
TI  - Synthesis of L-daunosamine and L-ristosamine glycosides via photoinduced
      aziridination. Conversion to thioglycosides for use in glycosylation reactions.
AB  - Application of photoinduced acylnitrene aziridination to the syntheses of L
      daunosamine and L-ristosamine glycosides is reported. Photoreaction of methyl 4-O
      azidocarbonyl-2,3,6-trideoxy-L-hex-2-enopyranosides, followed by aziridine
      opening, leads to 3-amino-3-N-,4-O-carbonyl-2,3,6-trideoxy precursors to the
      aminosugar methyl glycosides. Conversion of these precursors to their
      thioglycoside analogues followed by N-acetylation of the carbamate moiety permits
      high yielding and, in some cases, stereoselective glycosylations using the 1
      benzenesulfinylpiperidine-triflic anhydride activation method developed by Crich
      and co-workers. Glycosylations involving activation with N-iodosuccinimide and
      silver triflate were also successful, but the stereoselectivities of these
      reactions in general were lower.

PMID- 17025296
TI  - Synthesis of a core arabinomannan oligosaccharide of Mycobacterium tuberculosis.
AB  - The synthesis of a core arabinomannan (AM) oligosaccharide from Mycobacterium
      tuberculosis has been achieved using a convergent [6 + 6] glycosylation strategy
      and a defined set of building blocks. Dodecasaccharide 1, containing the key AM
      structural features of lipoarabinomannan (LAM), was obtained in excellent yield
      and selectivity from hexamannan 3 and hexaarabinan 5. This flexible synthetic
      strategy involves late-stage couplings and modifications, thus providing ready
      access to several different LAM fragments. The incorporation of a thiol linker at
      the reducing end of the oligosaccharide allows for the attachment of these
      compounds to microarrays and protein carriers.

PMID- 17025297
TI  - The profound effect of fluorine substitution on the reactivity and
      regioselectivity of nucleophilic substitution reactions of strained heterocycles.
      A study of aziridine and its derivatives.
AB  - Unlike the synthetically exploited oxiranes and thiiranes, aziridines that lack
      electron-withdrawing substituents, such as acyl or sulfonyl functionalities at
      nitrogen, are rather unreactive. As expected, three-membered aziridine 6 was
      calculated to be significantly more reactive than azetidine 7 in nucleophilic
      cleavage by ammonia, a typical nucleophile. The reactivity of 7 was about the
      same as that of an acyclic model compound, 8, when release of ring strain in the
      transition state was taken into account. Fluorine due to its similar size but
      vastly different electronegativity has been substituted for hydrogen as a means
      of modifying chemical properties for varied applications. In the present
      investigation, the effect of fluorine substitution at aziridine positions other
      than nitrogen was studied. Computations at the MP2(Full)/6
      311++G(d,p)//MP2(Full)/6-31+G(d) level found a vast preference for attack by
      ammonia at the 3-position of 2-fluoroaziridine in the gas phase at 298 K. When
      release of ring strain was taken into account, this compound reacted more than
      10(11) times faster than 6. The reaction rate with trans-2,3-difluoroaziridine
      was about twice that of 2-fluoroaziridine, while its diastereomer reacted with
      ammonia considerably slower. Acyclic fluorinated amine model compounds were
      employed to assess the generality of the effects produced by fluorine
      substitution. The results were rationalized by the energy contributions of strain
      energy releases, stabilization of the leaving group, and the relative
      electrostatic energies of the heterocycles in the transition states. The more
      reactive fluoroaziridines underwent nucleophilic attack at rates comparable to
      those of N-acetylaziridine.

PMID- 17025298
TI  - Synthesis and optical and redox properties of core-substituted naphthalene
      diimide dyes.
AB  - 2,6-Dichloronaphthalene dianhydride has been synthesized by a modified procedure.
      The imidization of this dichlorinated anhydride with amines and subsequent
      stepwise nucleophilic exchange of the chlorine atoms by alkyl- or arylamines
      afforded a series of hitherto unknown monoamino- and diamino-substituted
      naphthalene diimides. An alternative route for the synthesis of diamino
      substituted naphthalene diimides is also reported. Optical and electrochemical
      properties of the newly synthesized amino-functionalized naphthalene diimides
      were studied in detail. The absorption maxima (530-620 nm) of these dyes are
      appreciably bathochromically shifted compared to those of the corresponding core
      unsubstituted compounds. At the naphthalene core alkylamino-substituted diimides
      exhibit fluorescence quantum yields up to 60%.

PMID- 17025299
TI  - Five-to-six membered ring-rearrangements in the reaction of 5-perfluoroalkyl
      1,2,4-oxadiazoles with hydrazine and methylhydrazine.
AB  - The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine
      or methylhydrazine as bidentate nucleophiles has been investigated. The reaction
      occurred through the addition of the bidentate nucleophile to the C(5)-N(4)
      double bond of the 1,2,4-oxadiazole followed by ring-opening and ring-closure
      (ANRORC) involving the second nucleophilic site of the reagent. This ring-closure
      step could involve either the original C(3) of the 1,2,4-oxadiazole (giving a
      five-to-five membered ring rearrangement) or an additional electrophilic center
      linked to it (exploiting a five-to-six membered ring rearrangement). An
      alternative initial nucleophilic attack may involve the additional electrophilic
      center linked at C(3), that is the carbonyl group, leading to the formation of
      the hydrazones which undergo the Boulton-Katritzky rearrangement (BKR). The
      chosen reaction path is a function of the used nucleophile and of the nature of
      the substituent at C(3). At variance with previous hypotheses, when
      methylhydrazine was used, the observed regiochemistry always showed the preferred
      initial attack by the less hindered NH(2) end of the nucleophile on C(5).
      Moreover, new spectroscopic evidence allowed the assignment of correct structures
      to the products formed by reaction of 5-perfluoroalkyl-3-phenyl-1,2,4-oxadiazoles
      with methylhydrazine.

PMID- 17025300
TI  - Di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9-anthryl]-2,2,2-trifluoroethyl
      muconate: a highly chiral cavity for enantiodiscrimination by NMR.
AB  - A new chiral molecular tweezer, di-(R,R)-1-[10-(1-hydroxy-2,2,2-trifluoroethyl)-9
      anthryl]-2,2,2-trifluoroethyl muconate 2, was synthesized in enantiopure form,
      and its geometry was studied using NMR and molecular mechanics. The effectiveness
      of 2 as a chiral solvating agent for determining the enantiomeric composition of
      chiral compounds using NMR was demonstrated, improving the results obtained with
      other methods. The stoichiometry and the association constant of the resulting
      diastereomeric complexes were studied, and their geometry was analyzed by NOE and
      1H NMR.

PMID- 17025301
TI  - On gas phase alpha-effects. 1. The gas-phase manifestation and potential SET
      character.
AB  - The possibility of a gas-phase alpha-effect has been explored for the methyl
      transfer from methyl formate to hydroxide, hydroperoxide, and ethoxide by
      computing barrier heights at the HF/6-311++G(2df,2p) level of theory. The alpha
      nucleophile (hydroperoxide) is found to have a lower barrier than the gas-phase
      acidity-matched normal nucleophile (ethoxide) by 3.6 kcal/mol, offering evidence
      for a gas phase alpha-effect. A Shi-Boyd analysis for these reactions indicates
      that there is more single-electron-transfer character in the hydroperoxide
      transition state than for either hydroxide or ethoxide, further bolstering the
      existence of a gas-phase alpha-effect and the appropriateness of the Hoz model
      for the alpha-effect.

PMID- 17025302
TI  - Tandem pseudopericyclic reactions: [1,5]-X sigmatropic shift/6pi-electrocyclic
      ring closure converting N-(2-X-carbonyl)phenyl ketenimines into 2-X-quinolin
      4(3H)-ones.
AB  - N-(2-X-Carbonyl)phenyl ketenimines undergo, under mild thermal conditions, [1,5]
      migration of the X group from the carbonyl carbon to the electron-deficient
      central carbon atom of the ketenimine fragment, followed by a 6pi-electrocyclic
      ring closure of the resulting ketene to provide 2-X-substituted quinolin-4(3H)
      ones in a sequential one-pot manner. The X groups tested are electron-donor
      groups, such as alkylthio, arylthio, arylseleno, aryloxy, and amino. When
      involving alkylthio, arylthio, and arylseleno groups, the complete transformation
      takes place in refluxing toluene, whereas for aryloxy and amino groups the
      starting ketenimines must be heated at 230 degrees C in a sealed tube in the
      absence of solvent. The mechanism for the conversion of these ketenimines into
      quinolin-4(3H)-ones has been studied by ab initio and DFT calculations, using as
      model compounds N-(2-X-carbonyl)vinyl ketenimines bearing different X groups (X =
      F, Cl, OH, SH, NH(2), and PH(2)) converting into 4(3H)-pyridones. This
      computational study afforded two general reaction pathways for the first step of
      the sequence, the [1,5]-X shift, depending on the nature of X. When X is F, Cl,
      OH, or SH, the migration occurs in a concerted mode, whereas when X is NH(2) or
      PH(2), it involves a two-step sequence. The order of migratory aptitudes of the X
      substituents at the acyl group is predicted to be PH(2) > Cl > SH > NH(2) > F>
      OH. The second step of the full transformation, the 6pi-electrocyclic ring
      closure, is calculated to be concerted and with low energy barriers in all the
      cases. We have included in the calculations an alternative mode of cyclization of
      the N-(2-X-carbonyl)vinyl ketenimines, the 6pi-electrocyclic ring closure leading
      to 1,3-oxazines that involves its 1-oxo-5-aza-1,3,5-hexatrienic system.
      Additionally, the pseudopericyclic topology of the transition states for some of
      the [1,5]-X migrations (X = F, Cl, OH, SH), for the 6pi-electrocyclization of the
      ketene intermediates to the 4(3H)-pyridones, and for the 6pi-electrocyclization
      of the starting ketenimines into 1,3-oxazines could be established on the basis
      of their geometries, natural bond orbital analyses, and magnetic properties. The
      calculations predict that the 4(3H)-pyridones are the thermodynamically
      controlled products and that the 1,3-oxazines should be the kinetically
      controlled ones.

PMID- 17025303
TI  - Stereocontrolled formation of ketomethylene isosteres through tandem chain
      extension reactions.
AB  - A zinc-mediated chain extension reaction is the key step in the preparation of
      gamma-keto amides derived from amino acids. The use of tandem reaction sequences,
      in which the intermediate zinc enolate is trapped with electrophilic reagents,
      results in the incorporation of alpha-substituents, which mimic the side chains
      found in natural amino acid systems. Use of the chiral amino acid L-proline as a
      stereo-directing element provides a diastereoselective route to various
      ketomethylene isosteres.

PMID- 17025304
TI  - Synthesis of the G-C DNA base hybrid with a functional tail.
AB  - Molecules which possess the hydrogen bonding codes of both guanine and cytosine
      ("G-C DNA base hybrids") are known to organize in a hexagonal array both in
      solution and the solid state. Including an easily derivatizable functional group
      in the molecule allows the co-organization of virtually any species in the
      hexagonal periphery. Simple 5- and 6-step procedures are described for the
      synthesis of DNA base hybrids with tail groups which are terminated by
      electrophilic (primary bromide) and nucleophilic (primary alcohol) functions,
      respectively.

PMID- 17025305
TI  - Studies on the total synthesis of lactonamycin: synthesis of the CDEF ring
      system.
AB  - A concise and efficient synthesis of the tetracyclic CDEF ring system of
      lactonamycin (1) is described. The key step involved the Lewis acid mediated,
      intramolecular Friedel-Crafts acylation of carboxylic acid 6 to produce the
      tetracyclic CDEF core structure of target 1. The synthesis of 6 was carried out
      using a high-yielding Negishi coupling of benzyl bromide 7 with triflate 8, which
      was accessible in 11 steps and 31% overall yield on a multigram scale starting
      from trihydroxy acid 9.

PMID- 17025306
TI  - Screening of a modular sugar-based phosphite ligand library in the asymmetric
      nickel-catalyzed trialkylaluminum addition to aldehydes.
AB  - We synthesized a modular sugar-based phosphite ligand library for the Ni
      catalyzed trialkylaluminum addition to aldehydes. This library has been designed
      to rapidly screen the ligands to uncover their important structure features and
      determine the scope of the phosphite ligands in this catalytic reaction. After
      systematic variation of the sugar backbone, the substituents at the phosphite
      moieties, and the flexibility of the ligand backbone, the monophosphite ligand
      1,2:5,6-di-O-isopropylidene-3-O-((3,3';5,5'-tetra-tert-butyl-1,1'-biphenyl-2,2'
      diyl)phosphite)-alpha-D-glucofuranose 1c was found to be optimal, yielding high
      activities and enantioselectivities (ee's up to 94%) for several aryl aldehydes.

PMID- 17025307
TI  - New practical synthesis of indazoles via condensation of o-fluorobenzaldehydes
      and their O-methyloximes with hydrazine.
AB  - The reaction of o-fluorobenzaldehydes and their O-methyloximes with hydrazine has
      been developed as a new practical synthesis of indazoles. Utilization of the
      methyloxime derivatives of benzaldehydes (in the form of the major E-isomers) in
      this condensation effectively eliminated a competitive Wolf-Kishner reduction to
      fluorotoluenes, which was observed in the direct preparations of indazoles from
      aldehydes. Reaction of Z-isomers of methyloximes with hydrazine resulted in the
      formation of 3-aminoindazoles via a benzonitrile intermediate.

PMID- 17025308
TI  - Photochemistry of 1,2-dihydronaphthalene oxide: concurrent triplet and singlet
      processes via singlet excitation.
AB  - The photochemistry of 1,2-dihydronaphthalene oxide (254 nm) was reexamined and
      indan was found to be a primary photoproduct, as well as the traditionally
      assumed secondary photoproduct. Quenching studies demonstrated that indan, as a
      primary photoproduct, is derived from a triplet pathway, competing with a singlet
      route, back to the ground state surface. CASSCF calculations strongly suggest
      that the triplet pathway consists of a dissociation of the oxirane moiety to give
      a triplet carbene and aldehyde, which via hydrogen abstraction-decarbonylation
      ISC recloses to give indan. Conical intersections corresponding to the presumed
      1,2-hydrogen shift and 1,2-alkyl shift to give 2-tetralone and 1
      indancarbaldehyde, respectively, were located computationally.

PMID- 17025309
TI  - Fe(0)-mediated synthesis of tri- and tetra-substituted olefins from carbonyls: an
      environmentally friendly alternative to Cr(II).
AB  - Fe(0) was investigated as a cost-effective, environmentally friendly alternative
      to Cr(II) for the olefination of carbonyls by activated polyhalides. In many
      instances, Fe(0) was equivalent or superior to Cr(II). Notably, Fe(0), but not
      Cr(II), proved compatible with a wide range of functionality, inter alia,
      unprotected phenol, aryl nitro, carboxylic acid, and alkyl nitrile. A surprising
      reversal of stereoselectivity for aldehydes versus ketones was observed using
      both metals. The resultant alpha-halo-alpha,beta-unsaturated or alpha,beta
      unsaturated carboxylic acids, esters, and nitriles are common structural elements
      in numerous compounds of interest as well as key intermediates in the preparation
      of other functionality.

PMID- 17025310
TI  - Polyether macrocycles from intramolecular cyclopropanation and ylide formation.
      Effect of catalyst and coordination.
AB  - The use of catalytic metal carbene methodology with diazoacetates for the
      construction in high yield of polyether macrocycles having ring sizes greater
      than 25 has been achieved by preventing access to gamma-C-H positions for
      intramolecular insertion. Cyclopropanation is the exclusive outcome of reactions
      performed with dirhodium(II) catalysts, and product yields of greater than 70%
      are obtained without resorting to high dilution with solvents. With copper(I)
      catalysts having multiple sites for polyether coordination, intramolecular
      oxonium ylide formation occurs at the terminal oxygen, followed by [2,3]
      sigmatropic rearrangement of the pendant allyl group, in competition with
      cyclopropanation. Sodium ion coordination with the reactant diazo compound
      inhibits oxonium ylide formation in copper-catalyzed reactions. The composite
      results are consistent with copper serving as a template for the substrate as
      well as the site in the ether complex for diazo decomposition and subsequent
      metal carbene reactions.

PMID- 17025311
TI  - Enantioselective synthesis of protected L-4
      [sulfonamido(difluoromethyl)]phenylalanine and L-4
      [sulfonamido(methyl)]phenylalanine and an examination of hexa- and tripeptide
      platforms for evaluating pTyr mimics for PTP1B inhibition.
AB  - The first enantioselective syntheses of L-4-(sulfonamidomethyl)phenylalanine and
      L-[sulfonamido(difluoromethyl)]phenylalanine suitably protected for peptide
      syntheses are described. A key step in the synthesis of L
      (sulfonamidomethyl)phenylalanine was an oxidative chlorination on Ac-L-Phe(4
      CH2SCOCH3)-OEt to give crude Ac-L-Phe(4-CH2SO2Cl)-OEt, which could be reacted
      with amines to give the corresponding sulfonamides. Key to the preparation of L
      [sulfonamido(difluoromethyl)]phenylalanine was a highly enantioselective reaction
      involving William's auxiliary and a benzylic bromide intermediate. These amino
      acids were incorporated into two peptide sequences, DADE-X-LNH2 and FmocGlu(OBn)
      X-LNH2, which have previously been employed as platforms for assessing pTyr
      mimics for inhibition of protein tyrosine phosphatase 1B (PTP1B). Inhibition
      studies with these and other peptides and PTP1B revealed that good inhibition
      could be obtained using the tripeptide platform, although the presence of a pTyr
      mimic was not required for good inhibition. These results suggest that the
      FmocGlu(OBn)-X-LNH2 tripeptide platform is not suitable for assessing pTyr mimics
      for PTP1B inhibition.

PMID- 17025312
TI  - Sterically and electronically tunable and bifunctional organocatalysts: design
      and application in asymmetric aldol reaction of cyclic ketones with aldehydes.
AB  - Sterically and electronically tunable and bifunctional organocatalysts have been
      developed and evaluated in the direct aldol reaction of heterocyclic ketones.
      Catalysts with different substituents showed variable catalytic efficiency for
      analogous substrates, indicating the importance of fine-tuning the strength of
      the hydrogen bonding in the two NH groups. The reactions all proceeded in good to
      high yield and with excellent enantioselectivities ranging from 90% to >99% ee.
      In most cases, high diastereoselectivities ranging from 96/4 to 99/1 were
      obtained for the anti aldol adduct.

PMID- 17025313
TI  - Kinetics of proton transfer from benzo[b]-2,3-dihydrofuran-2-one and benzo[b]-2,3
      dihydrothiophene-2-one. Effect of anion aromaticity on intrinsic barriers.
AB  - Rates of the reversible deprotonation of benzo[b]-2,3-dihydrofuran-2-one (6H-O)
      and benzo[b]-2,3-dihydrothiophene-2-one (6H-S) by OH-, primary aliphatic amines,
      secondary alicyclic amines, and carboxylate ions have been determined in water at
      25 degrees C. As noted earlier by Kresge and Meng, 6H-S (pKa = 8.82) is
      considerably more acidic than 6H-O (pKa = 11.68), which mainly reflects the
      greater aromatic stabilization of the conjugate base of 6H-S (thiophene
      derivative) compared to that of 6H-O (furan derivative). The main focus of this
      paper is to assess how the difference in the aromaticity of the two enolate ions
      affects the intrinsic barrier to the proton transfer. These intrinsic barriers
      were determined from Bronsted plots for the reactions with the amines and
      carboxylate ions or calculated on the basis of the Marcus equation for the
      reactions with OH-. They are consistently somewhat higher for the reactions of 6H
      S than for the reactions of 6H-O, implying that the aromaticity in the anion
      enhances the intrinsic barrier. This contrasts with a previous report on the
      deprotonation of some cyclic rhenium Fischer-type carbene complexes where the
      reaction that leads to the most aromatic conjugate base (thiophene derivative)
      has a lower intrinsic barrier than the reaction that leads to the less aromatic
      furan analogue. We are offering a detailed analysis of other potential factors
      that may affect the intrinsic barriers and which could explain these
      contradictory results.

PMID- 17025314
TI  - Resolution, enantiomerization kinetics, and chiroptical properties of 7,7'
      dihydroxy-8,8'-biquinolyl.
AB  - (+/-)-7,7'-Dihydroxy-8,8'-biquinolyl (6) was resolved into its enantiomorphic
      atropisomers via reverse phase (C18) chromatographic separation of epimeric
      bismenthyl carbonates, (-)-lk-9 and (+)-ul-9, derived from 6 and (+)-menthyl
      chloroformate. The faster eluting diastereoisomer, (-)-lk-9, was revealed to
      possess an (aS)-configurated biaryl axis by X-ray crystallographic analysis.
      Saponification of the separated bismenthyl carbonates gave enantioenriched
      samples of biquinolyl 6, and absolute stereochemical configurations were assigned
      to the two optical isomers as (-)-(aS)-6 and (+)-(aR)-6 by correlation with their
      respective progenitors, (-)-lk-9 and (+)-ul-9. First-order rate constants for the
      enantiomerization of 6 in water were obtained over the temperature range 316-366
      K, and activation parameters were determined as DeltaH(++) = 34.0 kcal mol(-1)
      and DeltaS(++) = 18.7 cal mol(-1) K(-1) by Eyring plot analysis. A low level
      (AM1) computational study of the rotational dynamics of 6 showed excellent
      agreement with kinetic experimental data and suggested that enantiomerization
      occurs preferentially via a syn pathway. In common with (-)-(aS)-1,1'-bi-2
      naphthol (BINOL), (-)-(aS)-6 showed positive exciton chirality in its electronic
      circular dichroism (CD) spectrum and gave a characteristic couplet composed of a
      positive maximum Cotton effect at 250 nm and a negative minimum at 234 nm (Delta
      Delta epsilon = +40 M(-1) cm(-1) at 64% ee).

PMID- 17025315
TI  - Expanding the scope of the acyl-type radical addition reactions promoted by SmI2.
AB  - N-acyl oxazolidinones of simple carboxylic acids and amino acids were observed to
      undergo successful SmI2-promoted couplings with substituted acrylamides and
      acrylates, affording a variety of functionalized gamma-ketoamides and -esters
      with yields attaining 85%. As many of these reductive couplings were previously
      found to be ineffective employing the corresponding 4-pyridylthio esters, the
      applicability of this methodology has been substantially improved. The
      methodology has been adapted to prepare structures related to two potent
      aspartate protease inhibitors, the renin inhibitor aliskiren, and the gamma
      secretase inhibitor L-685,458. Finally, a convenient two-step procedure for the
      preparation of N-acyl oxazolidinones of N-protected amino acids, which provides
      consistently good yields of the corresponding imide, has been devised.

PMID- 17025316
TI  - Reactivity of triarylphosphine peroxyl radical cations generated through the
      reaction of triarylphosphine radical cations with oxygen.
AB  - One-electron oxidation of triarylphosphines (Ar3P, Ar = phenyl and substituted
      phenyl) in benzonitrile (PhCN) has been studied using pulse radiolysis technique.
      One-electron oxidation of Ar3P occurred to yield the radical cation (Ar3P*+)
      which showed an intense absorption with a peak at 360-370 nm together with a
      broad band at 500-600 nm. The addition of molecular oxygen (O2) to the phosphorus
      atom of Ar3P*+ took place at the second-order rate constant of 10(7)-10(9) dm(3)
      mol(-1) s(-1) to yield the peroxyl triarylphosphinyl radical cation (Ar3P+OO*).
      It is found that the electron-releasing substituents on the para position of the
      phenyl ring of Ar3P influence the rate constants of the reaction of Ar3P*+ with
      O2 and that o-methyl substituents on the phenyl ring influence the reactivity of
      Ar3P+OO*.

PMID- 17025317
TI  - Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E
      photoisomerization of cyclooctene included and sensitized by permethylated 6-O
      modified beta-cyclodextrins.
AB  - Permethylated 6-O-modified beta-cyclodextrins 2a-2d were synthesized as novel
      photosensitizing hosts with a flexible skeleton. Circular dichroism (CD) and 2D
      NMR spectral examinations of benzoate 2a revealed that the benzoate moiety is
      deeply included into its own cavity in aqueous solution. Upon addition of (Z)
      cyclooctene (1Z) to a 50% aqueous methanol solution of 2a at 25 degrees C, the
      benzoate moiety of 2a was gradually excluded from the cavity as indicated by the
      CD spectral changes; the Job's plot revealed the formation of a 1:1 complex of 2a
      with 1Z. The binding constants for the complexation of 1Z by 2a were determined
      by CD spectral titration in 50% aqueous methanol at various temperatures. The
      van't Hoff analysis of the obtained data afforded the thermodynamic parameters
      (DeltaH degrees = -3.1 kJ mol(-1), DeltaS degrees = 48.5 J mol(-1) K(-1)),
      demonstrating the entropy-driven complexation by the permethylated cyclodextrin.
      This is in sharp contrast to the complexation of 1Z by nonmethylated beta
      cyclodextrin benzoate that is driven by enthalpy (DeltaH degrees = -31.8 kJ mol(
      1) and DeltaS degrees = -51.1 J mol(-1) K(-1)). Upon supramolecular
      photosensitization with 2a-2d, 1Z isomerized to the (E)-isomer (1E) in moderate
      enantiomeric excesses (ee's), which however displayed significant temperature
      dependence with accompanying switching of the product's chirality in an extreme
      case. Such dynamic behavior of ee is very different from that reported for the
      photosensitization with nonmethylated cyclodextrin benzoate, where the product's
      ee is controlled by host occupancy. Eyring treatment of the ee obtained at
      various temperatures (<0 degrees C) gave the differential activation parameters
      for the enantiodifferentiation process occurring in the supramolecular exciplex,
      revealing the crucial role of entropy, as indicated by the DeltaDeltaS(++) value
      changing dynamically from +4 to -24 J K(-1) mol(-1). The origin of the
      contrasting behavior of permethylated versus nonmethylated cyclodextrin hosts is
      inferred to be the conformational flexibility of the former host, which enables
      the entropy-driven guest complexation in the ground state and the entropy
      controlled enantiodifferentiation in the excited state.

PMID- 17025318
TI  - A potentially valuable advance in the synthesis of carbohydrate-based anticancer
      vaccines through extended cycloaddition chemistry.
AB  - An advance in the long-term problem of joining complex oligosaccharides to
      polypeptides and even proteins is described herein. The key method involves
      equipping the oligosaccharide sector with an azide and the polypeptide with
      pendant alkynyl functionality. The two sectors are joined through a "click-like"
      cycloaddition. The method encompasses oligosaccharide constructs with several
      azide linkages which undergo concurrent cycloaddition to peptide-based
      acetylenes. This technology could well prove to be useful in the construction of
      fully synthetic vaccines.

PMID- 17025319
TI  - Quantifying the reactivity of a remarkably long-lived difluorinated enol in
      acidic methanol via solution kinetics and electronic structure calculations.
AB  - A simple enol acetal underwent rapid cleavage in acidic solution to generate a
      difluorinated enol, which was sufficiently long-lived to be characterized by 2D
      NMR in a protic solvent at ambient temperature. Density functional theory
      calculations on a model reaction suggest that there are significant differences
      in protonation transition state timing between the fluorinated and nonfluorinated
      enols.

PMID- 17025320
TI  - Divergent asymmetric synthesis of 3,5-disubstituted piperidines.
AB  - A divergent synthesis of various 3,5-dioxygenated piperidines with interesting
      pharmacological properties is described. A mixture of the achiral cis- and
      racemic trans-3,5-piperidine diol could be efficiently obtained from N
      benzylglycinate in five steps by the use of chemoenzymatic methods. In the
      subsequent enzyme- and Ru-catalyzed reaction, the rac/meso diol mixture was
      efficiently transformed to the cis-(3R,5S)-diacetate with excellent
      diastereoselectivity and in high yield. Further transformations of the cis
      diacetate selectively delivered the cis-piperidine diol and the cis-(3R,5S)
      hydroxy acetate. Alternatively, the DYKAT could be stopped at the monoacetate
      stage to give the trans-(3R,5R)-hydroxy acetate.

PMID- 17025321
TI  - Hypervalent iodine mediated intramolecular cyclization of thioformanilides:
      expeditious approach to 2-substituted benzothiazoles.
AB  - A new, mild, and efficient method has been developed for the synthesis of 2
      substituted benzothiazoles via the intramolecular cyclization of thioformanilides
      by using hypervalent iodine reagents in CH2Cl2 at ambient temperature. The
      reaction proceeds via a thiyl radical in high yields to give the novel compound
      oxybis benzothiazole and is also amenable to generating combinatorial libraries
      of heterocyclic compounds by solid-phase synthesis.

PMID- 17025322
TI  - A facile synthesis of the basic steroidal skeleton using a Pauson-Khand reaction
      as a key step.
AB  - A high-yield synthesis of steroid-type molecules under mild reaction conditions
      is achieved in two steps involving nucleophilic addition of alkynyl cerium
      reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an
      intramolecular Pauson-Khand reaction.

PMID- 17025323
TI  - Inexpensive, one-pot synthesis of unsymmetrical disulfides using 1
      chlorobenzotriazole.
AB  - A new synthesis of unsymmetrical disulfides is described. The reaction of a thiol
      R1SH with 1-chlorobenzotriazole (BtCl) at -78 degrees C in DCM affords a high
      yielding conversion to R1SBt without appreciable formation of the symmetrical
      disulfide R1SSR1. R1SBt is then reacted with R2SH to form the unsymmetrical
      disulfide in a one-pot sequence with green character that avoids the use of toxic
      and harsh oxidizing agents. The methodology has been developed for synthesis of
      various types of disulfides.

PMID- 17025324
TI  - One-step heterylation at the upper rim of calix[4]arene with 1,2,4-triazin-5(2H)
      ones.
AB  - A convenient way to modify calix[4]arenes based on the direct C-C coupling
      reaction of their phenol moiety with 1,2,4-triazines has been advanced, and the
      ability of modified calixarenes to provide transport of La3+ and Ga3+ cations
      through organic membranes has been examined.

PMID- 17025325
TI  - Enantioselective synthesis of (R)- and (S)-alpha-alkylcysteines via phase
      transfer catalytic alkylation.
AB  - We reported efficient enantioselective synthetic methodologies for (R)-alpha
      alkylcysteines and (S)-alpha-alkylcysteines. The phase-transfer catalytic
      alkylation of 2-phenyl-2-thiazoline-4-carboxylic acid tert-butyl ester and 2-o
      biphenyl-2-thiazoline-4-carboxylic acid tert-butyl ester, in the presence of
      chiral catalysts (1 or 2), gave the corresponding alkylated products, which could
      be hydrolyzed to provide (R)-alpha-alkylcysteines (67->99% ee) and (S)-alpha
      alkylcysteines (66-88% ee), respectively.

PMID- 17025326
TI  - Fluoride ion-triggered dual fluorescence switch based on naphthalimides winged
      zinc porphyrin.
AB  - A novel fluoride ion-triggered dual fluorescence molecular switch based on
      naphthalimides winged zinc porphyrin (1) was designed and prepared. The
      fluorescence of the zinc porphyrin unit could be regulated "ON-OFF" on the
      excitation of 365 nm and "OFF-ON" on the excitation of 504 nm, respectively, in
      the presence of fluoride ion. The obvious color changes induced by the
      intermolecular proton transfer on N-H fragments are clearly visible to the naked
      eye.

PMID- 17025327
TI  - Molecular iodine-catalyzed facile procedure for N-Boc protection of amines.
AB  - An efficient and practical protocol for the protection of various structurally
      and electronically divergent aryl and aliphatic amines using (Boc)2O in the
      presence of a catalytic amount of molecular iodine (10 mol %) under solvent-free
      conditions at ambient temperature is presented.

PMID- 17025328
TI  - Aryl-substituted sulfonium betaines: preparation and use in the epoxidation of
      aldehydes.
AB  - Thermally induced decarboxylation of carboxymethylsulfonium betaines results in
      formation of the corresponding sulfur ylides in situ. Decarboxylation rates for a
      range of arylcarboxymethylsulfonium betaine salts have been determined using NMR
      spectroscopy, and the efficiency of ylide generation and trapping has been
      evaluated via methylidene transfer to a range of aldehydes to form epoxides.

PMID- 17025329
TI  - A general synthetic route to 6,6-substituted-6H-dibenzo[b,d]pyrans from
      dibenzofuran.
AB  - The reaction of dibenzofuran 1, lithium pieces (2.2 equiv), and TMEDA (2.2 equiv)
      in dry ether under reflux led to a solution of the corresponding C,O-dilithiated
      intermediate 2 which, upon treatment with different ketones or aldehydes (0.8
      equiv) at -78 degrees C, afforded, after hydrolysis and dehydration, 6,6
      substituted-6H-dibenzo[b,d]pyrans 3 in good yields. The reaction undergoes
      reductive ring opening and cyclization, and the intermediate diol 4e was
      isolated.

PMID- 17025330
TI  - De novo synthesis of aceric acid and an aceric acid building block.
AB  - The de novo synthesis of an aceric acid thioglycoside building block and the
      total synthesis of the plant carbohydrate aceric acid are described via a highly
      convergent strategy. Aldol reaction of acetaldehyde and a protected tartaric acid
      derivative provided the open chain carbohydrate. Subsequent acid treatment
      yielded the aceric acid thioglycoside in 35% total yield over five steps.
      Oxidative cleavage of the thioketal in the open chain carbohydrate and basic
      hydrolysis of the methyl ester furnished fully deprotected aceric acid in 31%
      yield over six steps.

PMID- 17025331
TI  - A general and efficient FeCl3-catalyzed nucleophilic substitution of propargylic
      alcohols.
AB  - A general and efficient FeCl3-catalyzed substitution reaction of propargylic
      alcohols with carbon- and heteroatom-centered nucleophiles such as allyl
      trimethylsilane, alcohols, aromatic compounds, thiols, and amides, leading to the
      construction of C-C, C-O, C-S and C-N bonds, has been developed.

PMID- 17025333
TI  - Guerbet reaction of primary alcohols leading to beta-alkylated dimer alcohols
      catalyzed by iridium complexes.
AB  - [IrCl(cod)]2 and [Cp*IrCl2]2 complexes catalyzed efficiently the Guerbet reaction
      of primary alcohols to beta-alkylated dimer alcohols in good yields. For
      instance, the reaction of 1-butanol in the presence of [Cp*IrCl2]2 (1 mol %), t
      BuOK (40 mol %), and 1,7-octadiene (10 mol %) produced 2-ethyl-1-hexanol in 93%
      yield. Various primary alcohols undergo the Guerbet reaction under the influence
      of Ir complexes to give the corresponding dimer alcohols in good yields. This
      method provides an alternative direct route to beta-alkylated primary alcohols
      which are prepared by aldol condensation of aldehydes followed by hydrogenation.

PMID- 17025332
TI  - An efficient synthesis of a potent PPARpan agonist.
AB  - An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2
      [4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2
      methylpropanoic acid (1), a potent PPARpan agonist, is described. The seven-step
      synthesis, which afforded 1 in 30% overall yield, includes a highly
      regioselective carbon-sulfur bond formation via coupling of a
      bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the
      remaining alcohol through a three-step telescoped sequence involving an efficient
      cleavage of an aryl mesylate, and an efficient and practical method of
      introducing an isobutyric acid fragment.

PMID- 17025334
TI  - Palladium-catalyzed selective 2,3-diarylation of alpha,alpha-disubstituted 3
      thiophenemethanols via cleavage of C-H and C-C bonds.
AB  - Alpha,alpha-disubstituted 3-thiophenemethanols undergo selective diarylation
      accompanied by cleavage of the C-H and C-C bonds of the 2- and 3-positions,
      respectively, upon treatment with aryl bromides in the presence of a palladium
      catalyst to give the corresponding 2,3-diarylthiophenes in good yields.

PMID- 17025335
TI  - Nickel-catalyzed synthesis of benzocoumarins: application to the total synthesis
      of arnottin I.
AB  - The ring-opening addition of methyl 2,3-dimethoxy-6-iodobenzoate to
      oxabenzonorbornadienes followed by cyclization in the presence of NiBr2(dppe) and
      Zn metal powder in acetonitrile at 80 degrees C to give the corresponding
      benzocoumarin derivatives is described. This methodology was then applied to the
      synthesis of natural product arnottin I, first isolated from Xanthoxylum
      arnottianum Maxim, using protecting group chemistry. After deprotection and
      subsequent ring closure, arnottin I was obtained in 21% overall yield after six
      steps starting from catechol.

PMID- 17025336
TI  - A metal-free approach to the synthesis of indoline derivatives by a
      phenyliodine(III) bis(trifluoroacetate)-mediated amidohydroxylation reaction.
AB  - A novel approach to the synthesis of indoline derivatives is presented. The key
      cyclization step features the phenyliodine(III) bis(trifluoroacetate)- (PIFA-)
      mediated formation of a N-acylnitrenium ion and its succeeding intramolecular
      trapping by the olefin fragment. In addition, difunctionalization of the alkene
      moiety is achieved since the in situ generation of an additional hydroxy group at
      the terminal position of the original double bond accompanies the intramolecular
      C-N bond formation.

PMID- 17025337
TI  - Highly enantioselective alpha-aminoxylation of aldehydes and ketones in ionic
      liquids.
AB  - As the first example for the synthesis of optically active alpha-hydroxyaldehydes
      and alpha-hydroxyketones in ionic liquids, we applied RTILs into L-proline
      catalyzed direct enantioselective alpha-aminoxylation of both aldehydes and
      ketones successfully. This protocol features a number of advantages, such as
      recycling of green solvents and chiral organocatalyst, high yields, excellent
      enantioselectivities, short reaction times, and broad substrate scope.

PMID- 17025338
TI  - 2-aminopyrimidine-4,6-diol as an efficient ligand for solvent-free copper
      catalyzed N-arylations of imidazoles with aryl and heteroaryl halides.
AB  - Efficient and solvent-free copper-catalyzed N-arylations of imidazoles with aryl
      and heteroaryl halides have been demonstrated. In the presence of CuBr, 2
      aminopyrimidine-4,6-diol, and TBAF (n-Bu4NF), a variety of imidazoles underwent
      the N-arylation reaction with aryl and heteroaryl halides smoothly in moderate to
      excellent yields. Noteworthy is that the reaction is conducted under solvent-free
      conditions.

PMID- 17025341
TI  - Tissue engineering of small intestine--current status.
AB  - Short bowel syndrome (SBS) has always posed a great threat to patients and has
      been one of the biggest challenges for doctors due to its high morbidity and
      mortality. So far, parenteral nutrition (PN) and small bowel transplantation
      remain the only viable therapeutic options. However, sepsis and liver failure
      associated with PN and limited availability of the donor organs and high graft
      rejection rates associated with transplantation have limited their use to a
      nonpermanent solution. Clearly, there is a need for an alternative therapy
      whereby increasing the absorptive surface area would help neonates and adults
      suffering from permanent intestinal failure. Techniques such as sequential
      intestinal lengthening are being explored in animal models with little success.
      Attempts to engineer small intestine since the late 1980s have achieved varying
      degrees of success in animal models with evolving refinements in biotechnology.
      The most encouraging results so far have been the generation of intestinal
      neomucosa in the form of cysts when intestinal epithelial organoid units isolated
      from neonatal rats were seeded onto biodegradable polymers before implantation in
      syngeneic adult rats' omentum. Although still experimental, continued attempts
      worldwide using cultured stem cells and improved polymer technology offer promise
      to provide an off-the-shelf artificial intestine as a novel therapy for patients
      with SBS. This article reviews the current status of progress in the field of
      small intestinal tissue engineering and addresses various types of cell sources
      and scaffold material having potential to be used in this field.

PMID- 17025342
TI  - Stability improvement of electrospun chitosan nanofibrous membranes in neutral or
      weak basic aqueous solutions.
AB  - Further utilization of chitosan nanofibrous membranes that are electrospun from
      chitosan solutions in trifluoroacetic acid (TFA) with or without dichloromethane
      (DCM) as the modifying cosolvent is limited by the loss of the fibrous structure
      as soon as the membranes are in contact with neutral or weak basic aqueous
      solutions due to complete dissolution of the membranes. Dissolution occurs as a
      result of the high solubility in these aqueous media of -NH(3)(+)CF(3)COO(-) salt
      residues that are formed when chitosan is dissolved in TFA. Traditional
      neutralization with a NaOH aqueous solution only maintained partial fibrous
      structure. Much improvement in the neutralization method was achieved with the
      saturated Na(2)CO(3) aqueous solution with an excess amount of Na(2)CO(3)(s) in
      the solution. We showed that electrospun chitosan nanofibrous membranes, after
      neutralization in the Na(2)CO(3) aqueous solution, could maintain its fibrous
      structure even after continuous submersion in phosphate buffer saline (pH = 7.4)
      or distilled water for 12 weeks.

PMID- 17025343
TI  - Enzyme-responsive release of encapsulated proteins from biodegradable hollow
      capsules.
AB  - Biodegradable hollow capsules encapsulating proteins were prepared via layer-by
      layer assembly of chitosan and dextran sulfate on protein-entrapping mesoporous
      silica particles and the subsequent removal of the silica. The enzymatic
      degradation of the capsules in the presence of chitosanase was explored by
      scanning electron microscopy (SEM). With increasing time, the chitosan component
      was degraded by chitosanase, and the capsules began to deform and were finally
      destroyed. Sustained release of the encapsulated proteins was attained by using
      the enzymatic degradation of the hollow capsules. The release behavior was
      successfully manipulated by altering the charge of capsule surface.

PMID- 17025344
TI  - Self-assembled gold nanoshells on biodegradable chitosan fibers.
AB  - A novel chitosan fiber core/gold shell structural organic-inorganic composite was
      presented via a facile and eco-friendly approach. The chitosan fiber and
      gold/chitosan composites were characterized with the assistance of scanning
      electron microscopy and transmission electron microscopy observations. The
      chitosan fibers used in this study were 50 nm to 5 microm in diameter and up to
      hundreds of micrometers in length. The gold shells were typically 20-50 nm in
      depth, and their lattice fringes obliquely intersecting at an angle of 60 degrees
      were displayed. The formation mechanism of the as-fabricated chitosan fiber core
      with gold as the shell structural composites was also schematically discussed.

PMID- 17025345
TI  - Chitosan graft copolymer nanoparticles for oral protein drug delivery:
      preparation and characterization.
AB  - Several novel functionalized graft copolymer nanoparticles consisting of chitosan
      (CS) and the monomer methyl methacrylate (MMA), N-dimethylaminoethyl methacrylate
      hydrochloride (DMAEMC), and N-trimethylaminoethyl methacrylate chloride (TMAEMC),
      which show a higher solubility than chitosan in a broader pH range, have been
      prepared by free radical polymerization. The nanoparticles were characterized in
      terms of particle size, zeta potential, TEM, and FT-IR. These nanoparticles were
      150-280 nm in size and carried obvious positive surface charges. Protein-loaded
      nanoparticles were prepared, and their maximal encapsulation efficiency was up to
      100%. In vitro release showed that these nanoparticles provided an initial burst
      release followed by a slowly sustained release for more than 24 h. These graft
      copolymer nanoparticles enhanced the absorption and improved the bioavailability
      of insulin via the gastrointestinal (GI) tract of normal male Sprague-Dawley (SD)
      strain rats to a greater extent than that of the phosphate buffer solution (PBS)
      of insulin.

PMID- 17025346
TI  - Molecular weight dependence of the poly(L-lactide)/poly(D-lactide) Stereocomplex
      at the air-water interface.
AB  - The molecular weight dependence of poly(L-lactide)/poly(D-lactide) (PLLA/PDLA)
      stereocomplex behavior at the air-water interface was studied by surface pressure
      area (pi-A) isotherms and atomic force microscopy (AFM). It was found that the
      compression-induced sterecomplexation of a PDLA/PLLA equimolar blend with high
      molecular weight (M(w) = 1 x 10(6) and 9.8 x 10(5), respectively) could occur at
      the air-water interface. This result is in marked contrast with the
      stereocomplexation of PDLA/PLLA blends in the bulk from the melt or in solutions,
      where the homocrystallites of either PLLA or PDLA rather than stereocomplex
      crystallites will be formed preferentially when the molecular weights of both
      polymers are higher than 1 x 10(5). Unexpectedly, the Langmuir-Blodgett behavior
      of the PDLA/PLLA blend with lower molecular weight (M(w) = 4 x 10(3) and 3.2 x
      10(3), respectively), which should be favored in the stereocomplex, was distinct
      from that of other higher molecular weight blends. AFM images clearly disclosed
      for the first time the morphological changes of the equimolar blends of PLLA and
      PDLA at the air-water interface induced by increasing the surface pressure of the
      monolayer. Of particular note, the bilayer mechanism for the plateau in the
      isotherm was directly verified by the AFM height images.

PMID- 17025347
TI  - Controlling the aggregation of conjugates of streptavidin with smart block
      copolymers prepared via the RAFT copolymerization technique.
AB  - Block copolymers containing stimuli-responsive segments provide important new
      opportunities for controlling the activity and aggregation properties of protein
      polymer conjugates. We have prepared a RAFT block copolymer of a biotin
      terminated poly(N-isopropylacrylamide) (PNIPAAm)-b-poly(acrylic acid) (PAA). The
      number-average molecular weight (M(n)) of the (PNIPAAm)-b-(PAA) copolymer was
      determined to be 17.4 kDa (M(w)/M(n) = 1.09). The PNIPAAm block had an M(n) of
      9.5 kDa and the poly(acrylic acid) (PAA) block had an M(n) of 7.9 kDa. We
      conjugated this block copolymer to streptavidin (SA) via the terminal biotin on
      the PNIPAAm block. We found that the usual aggregation and phase separation of
      PNIPAAm-SA conjugates that follow the thermally induced collapse and dehydration
      of PNIPAAm (the lower critical solution temperature (LCST) of PNIPAAm is 32
      degrees C in water) is prevented through the shielding action of the PAA block.
      In addition, we show that the cloud point and aggregation properties (as measured
      by loss in light transmission) of the [(PNIPAAm)-b-(PAA)]-SA conjugate also
      depended on pH. At pH 7.0 and at temperatures above the LCST, the block copolymer
      alone was found to form particles of ca. 60 nm in diameter, while the
      bioconjugate exhibited very little aggregation. At pH 5.5 and 20 degrees C, the
      copolymer alone was found to form large aggregates (ca. 218 nm), presumably
      driven by hydrogen bonding between the -COOH groups of PAA with other -COOH
      groups and also with the -CONH- groups of PNIPAAm. In comparison, the conjugate
      formed much smaller particles (ca. 27 nm) at these conditions. At pH 4.0,
      however, large particles were formed from the conjugate both above and below the
      LCST (ca. 700 and 540 nm, respectively). These results demonstrate that the
      aggregation properties of the block copolymer-SA conjugate are very different
      from those of the free block copolymer, and that the outer-oriented hydrophilic
      block of PAA shields the intermolecular aggregation of the block copolymer-SA
      bioconjugate at pH values where the -COOH groups of PAA are significantly
      ionized.

PMID- 17025348
TI  - Biorecognition through layer-by-layer polyelectrolyte assembly: in-situ
      hybridization on living cells.
AB  - Encapsulated cells were formed from the assembly of cationic and anionic
      alternating layers using a number of polyelectrolyte-based systems. Chitosan,
      alginate, hyaluronic acid, and oligonucleotides were used as polyelectrolytes to
      encapsulate individual E. coli cells, which were used as a model. Zeta potential
      measurements taken for both chitosan/alginate and chitosan/hyaluronic acid
      systems indicate successful layer-by-layer (LbL) deposition and gave full
      reversal of the surface change eight times. Layer adsorption was further observed
      by fluorescence microscopy, and, through a newly developed protocol for sample
      preparation, transmission electron microscopy micrographs clearly showed the
      presence of LbL assembly on the outer layer of the cell membrane, in the
      nanometer range. A second generation of E. coli cells could be grown from
      encapsulated first generation cells, demonstrating that the cellular activity was
      not affected by the presence of polyelectrolyte multilayers. Hybridization
      between attached oligonucleotide sequences and the complementary sequence was
      demonstrated by both fluorescence spectroscopy and microscopy. Fluorescence
      energy transfer data recorded after hybrid formation showed that at a molar ratio
      of 10:20 (donor:acceptor), Q and I were 92.3% and 52.5%, respectively, which
      suggests that fluorescein fluorescence was quenched by 92.3% and that the
      fluorescence of rhodamine was enhanced by 52.5%. Oligonucleotide incorporation
      was stabilized by deposition of four alternating layers, hence offering not only
      the potential use of the encapsulated cell as a bio-recognition system but also
      its application in a number of fields such as oligonucleotide delivery, gene
      therapy, and the use of DNA as an immunocompatible coating.

PMID- 17025349
TI  - From natural products to polymeric derivatives of "eugenol": a new approach for
      preparation of dental composites and orthopedic bone cements.
AB  - Polymers with eugenol moieties covalently bonded to the macromolecular chains
      were synthesized for potential application in orthopedic and dental cements.
      First, eugenol was functionalized with polymerizable groups. The synthetic
      methods employed afforded two different methacrylic derivatives, where the
      acrylic and eugenol moieties were either directly bonded, eugenyl methacrylate
      (EgMA), or separated through an oxyethylene group, ethoxyeugenyl methacrylate
      (EEgMA). A typical Fisher esterification reaction was used for the synthesis of
      EgMA and EEgMA, affording the desired monomers in 80% yields. Polymerization of
      each of the novel monomers, at low conversion, provided soluble polymers
      consisting of hydrocarbon macromolecules with pendant eugenol moieties. At high
      conversions only cross-linked polymers were obtained, attributed to participation
      of the allylic double bonds in the polymerization reaction. In addition,
      copolymers of each eugenol derivative with ethyl methacrylate (EMA) were prepared
      at low conversion, with the copolymerization reaction studied by assuming the
      terminal model and the reactivity ratios determined according to linear and
      nonlinear methods. The values obtained were r(EgMA) = 1.48, r(EMA) = 0.55 and
      r(EEgMA) = 1.22, r(EMA) = 0.42. High molecular weight polymers and copolymers
      were obtained at low conversion. Analysis of thermal properties revealed a T(g)
      of 95 degrees C for PEgMA and of 20 degrees C for PEEgMA and an increase in the
      thermal stability for the eugenol derivatives polymers and copolymers with
      respect to that of PEMA. Water sorption of the copolymers was found to decrease
      with the eugenol derivative content. Both monomers EgMA and EEgMA showed
      antibacterial activity against Streptococcus mutans, producing inhibition halos
      of 7 and 21 mm, respectively. Finally, cell culture studies revealed that the
      copolymers did not leach any toxic eluants and showed good cellular proliferation
      with respect to PEMA. This study thus indicates that the eugenyl methacrylate
      derivatives are potentially good candidates for dental and orthopedic cements.

PMID- 17025350
TI  - Surface-active antifungal polyquaternary amine.
AB  - There is a distinct need for antimicrobial compounds that can act at surfaces
      without leaching into the environment. Such materials should be easy to
      synthesize, be easy to apply to surfaces, and display reasonable levels of
      antimicrobial and antifungal activity. Here we describe such a surface-active
      compound and demonstrate its ability to inhibit the growth of the filamentous
      fungus Aspergillus niger. We have synthesized a series of polyquaternary ammonium
      compounds by atom transfer radical polymerization. Two members of this series
      were tested for their ability to inhibit the growth of A. niger. The compounds
      were dried onto surfaces, and the treated surfaces were then used as growth
      chambers for A. niger. A water soluble polyquaternary amine compound was shown to
      effectively kill A. niger in solution in a dose-dependent manner. Conversely, a
      water insoluble polyquaternary amine compound was shown to kill only the fungi in
      direct contact with the material on the surface. These results have important
      implications for the development of effective, environmentally benign, surface
      active anti-fungal compounds.

PMID- 17025351
TI  - Micro/nanoscale well and channel fabrication on organic polymer substrates via a
      combination of photochemical and alkaline hydrolysis etchings.
AB  - With the utilization of photomasks, micro/nanoscale wells and channels with
      depths ranging from nanometers to several micrometers were fabricated on a
      poly(ethylene terephthalate) (PET) surface by a simple combination of
      photochemical and alkaline hydrolysis etching. The PET surface region could be
      directly and photochemically etched by UV light and N,N-dimethylformamide (DMF)
      to create 125-350 nm etching depths (step 1). In step 2, the depth could be
      further enlarged to 250-1400 nm by potassium hydroxide (KOH) developing. More
      importantly, when this combination etching was repeated with the same photomask,
      the depth increased with increasing etching times. For instance, the depth
      reached approximately 6 microm after a series of three combination etchings. The
      cross-sectional shape of the final structure was trapezoidal with smooth corners.
      No obvious widening effect in lateral size was observed after one combination
      etching, whereas the top width of the microfabricated channels was enlarged from
      50 microm (the designed feature of the photomask used) to 100 microm after two or
      three combination etchings. Even more interesting was that step 1 resulted in the
      formation of a kind of aminated surface in the channel (6.5% amine content), but
      when step 2 was conducted, the aminated surface was erased. This process could be
      reversibly carried out by repeating step 1 (amination) and step 2 (erasing).
      Electrostatical self-assembly of an antibody, fluorescein isothiocyanate-labeled
      immunoglobulin G (FITC-IgG, goat anti-rabbit), was achieved on the aminated
      surface of the etched channels, which demonstrated that by this combination
      strategy, micro/nanoscale channels or wells featuring tunable depths and
      functional channel surfaces could be readily fabricated. Undoubtedly, these
      functionalized channels or wells onto organic substrates could provide a
      potential platform for microchips toward various functions such as microarrays,
      heterogeneous immunoassays, biosensors, concentrations, filtrations, and
      microanalysis.

PMID- 17025352
TI  - Thermoreversible protein hydrogel as cell scaffold.
AB  - A thermoreversible fibrillar hydrogel has been formed from an aqueous lysozyme
      solution in the presence of dithiothreitol (DTT). Its physical properties and
      potential as a tissue engineering scaffold have been explored. Hydrogels were
      prepared by dissolving 3 mM protein in a 20 mM DTT/water mixture, heating to 85
      degrees C and cooling at room temperature. No gel was observed for the equivalent
      sample without DTT. The elastic nature of the gel formed was confirmed by
      rheology, and the storage modulus of our gel was found to be of the same order of
      magnitude as for other cross-linked biopolymers. Micro differential scanning
      calorimetry (microDSC) experiments confirmed that the hydrogel was thermally
      reversible and that gelation and melting occurs through a solid-liquid-like first
      order transition. Infrared spectroscopy of the hydrogel and transmission electron
      microscopy studies of very dilute samples revealed the presence of beta-sheet
      rich fibrils that were approximately 4-6 nm in diameter and 1 mum in length.
      These fibrils are thought to self-assemble along their long axes to form larger
      fibers that become physically entangled to form the three-dimensional network
      observed in both cryo-scanning electron microscopy (cryo-SEM) and small-angle
      neutron scattering (SANS) studies. The hydrogel was subsequently cultured with
      3T3 fibroblasts and cells spread extensively after 7 days and stretched actin
      filaments formed that were roughly parallel to each other, indicating the
      development of organized actin filaments in the form of stress fibers in cells.

PMID- 17025353
TI  - Characterization of nano-clay reinforced phytagel-modified soy protein
      concentrate resin.
AB  - Phytagel and nano-clay particles were used to improve the mechanical and thermal
      properties and moisture resistance of soy protein concentrate (SPC) resin
      successfully. SPC and Phytagel were mixed together to form a cross-linked
      structure. The Phytagel-modified SPC resin (PH-SPC) showed improved tensile
      strength, modulus, moisture resistance, and thermal stability as compared to the
      unmodified SPC resin. The incorporation of 40% Phytagel and 20% glycerol led to
      an overall 340% increase in the tensile strength (over 50 MPa) and approximately
      360% increase in the Young's modulus (over 710 MPa) of the SPC resin. Nano-clay
      was uniformly dispersed into PH-SPC resin to further improve the properties. The
      PH-SPC (40% Phytagel) resin modified with 7% clay nanoparticles (CPH-SPC) had a
      modulus of 2.1 GPa and a strength of 72.5 MPa. The dynamic mechanical properties
      such as storage modulus together with the glass transition temperature of the
      modified resins were also increased by the addition of clay nanoparticles. The
      moisture resistance of the CPH-SPC resin was higher as compared to both SPC and
      PH-SPC resins. The thermal stability of the CPH-SPC resin was seen to be higher
      as compared to the unmodified SPC.

PMID- 17025354
TI  - In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8
      and PEG-(PDLA)8 star block copolymers.
AB  - Eight-arm poly(ethylene glycol)-poly(L-lactide), PEG-(PLLA)(8), and poly(ethylene
      glycol)-poly(D-lactide), PEG-(PDLA)(8), star block copolymers were synthesized by
      ring-opening polymerization of either L-lactide or D-lactide at room temperature
      in the presence of a single-site ethylzinc complex and 8-arm PEG (M(n) = 21.8 x
      10(3) or 43.5 x 10(3)) as a catalyst and initiator, respectively. High lactide
      conversions (>95%) and well-defined copolymers with PLLA or PDLA blocks of the
      desired molecular weights were obtained. Star block copolymers were water-soluble
      when the number of lactyl units per poly(lactide) (PLA) block did not exceed 14
      and 17 for PEG21800-(PLA)(8) and PEG43500-(PLA)(8), respectively. PEG-(PLA)(8)
      stereocomplexed hydrogels were prepared by mixing aqueous solutions with
      equimolar amounts of PEG-(PLLA)(8) and PEG-(PDLA)(8) in a polymer concentration
      range of 5-25 w/v % for PEG21800-(PLA)(8) star block copolymers and of 6-8 w/v %
      for PEG43500-(PLA)(8) star block copolymers. The gelation is driven by
      stereocomplexation of the PLLA and PDLA blocks, as confirmed by wide-angle X-ray
      scattering experiments. The stereocomplexed hydrogels were stable in a range from
      10 to 70 degrees C, depending on their aqueous concentration and the PLA block
      length. Stereocomplexed hydrogels at 10 w/v % polymer concentration showed larger
      hydrophilic and hydrophobic domains as compared to 10 w/v % single enantiomer
      solutions, as determined by cryo-TEM. Correspondingly, dynamic light scattering
      showed that 1 w/v % solutions containing both PEG-(PLLA)(8) and PEG-(PDLA)(8)
      have larger "micelles" as compared to 1 w/v % single enantiomer solutions. With
      increasing polymer concentration and PLLA and PDLA block length, the storage
      modulus of the stereocomplexed hydrogels increases and the gelation time
      decreases. Stereocomplexed hydrogels with high storage moduli (up to 14 kPa)
      could be obtained at 37 degrees C in PBS. These stereocomplexed hydrogels are
      promising for use in biomedical applications, including drug delivery and tissue
      engineering, because they are biodegradable and the in-situ formation allows for
      easy immobilization of drugs and cells.

PMID- 17025355
TI  - Electrospun poly(epsilon-caprolactone) microfiber and multilayer
      nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of
      cellular infiltration.
AB  - The physical and spatial architectural geometries of electrospun scaffolds are
      important to their application in tissue engineering strategies. In this work,
      poly(epsilon-caprolactone) microfiber scaffolds with average fiber diameters
      ranging from 2 to 10 microm were individually electrospun to determine the
      parameters required for reproducibly fabricating scaffolds. As fiber diameter
      increased, the average pore size of the scaffolds, as measured by mercury
      porosimetry, increased (values ranging from 20 to 45 microm), while a constant
      porosity was observed. To capitalize on both the larger pore sizes of the
      microfiber layers and the nanoscale dimensions of the nanofiber layers, layered
      scaffolds were fabricated by sequential electrospinning. These scaffolds
      consisted of alternating layers of poly(epsilon-caprolactone) microfibers and
      poly(epsilon-caprolactone) nanofibers. By electrospinning the nanofiber layers
      for different lengths of time, the thickness of the nanofiber layers could be
      modulated. Bilayered constructs consisting of microfiber scaffolds with varying
      thicknesses of nanofibers on top were generated and evaluated for their potential
      to affect rat marrow stromal cell attachment, spreading, and infiltration. Cell
      attachment after 24 h did not increase with increasing number of nanofibers, but
      the presence of nanofibers enhanced cell spreading as evidenced by stronger F
      actin staining. Additionally, increasing the thickness of the nanofiber layer
      reduced the infiltration of cells into the scaffolds under both static and flow
      perfusion culture for the specific conditions tested. The scaffold design
      presented in this study allows for cellular infiltration into the scaffolds while
      at the same time providing nanofibers as a physical mimicry of extracellular
      matrix.

PMID- 17025356
TI  - Organophosphorus hydrolase at the air-water interface: secondary structure and
      interaction with paraoxon.
AB  - The secondary structure of organophosphorus hydrolase (OPH) at the air-water
      interface was studied using polarization modulation infrared reflection
      absorption spectroscopy (PM-IRRAS). The shape and position of the amide I and
      amide II bands were used to estimate the surface conformation and orientation of
      OPH. The PM-IRRAS results indicated that the enzyme did not unfold for the range
      of surface pressure used (0-30 mN/m). At low surface pressures, the signal of
      amide I was very weak and the intensity was almost the same as amide II. Upon
      further compression, the PM-IRRAS signal and the ratio of the intensity of amide
      I and amide II both increase, implying an increased interfacial concentration of
      the enzyme. From the amide I/amide II ratio and the band position, it was deduced
      that the enzyme adopts a conformation which gives a higher occupied surface at
      low surface pressure and rotates to a more vertical orientation at high surface
      pressures. The compression and decompression of the OPH monolayer indicated that
      the fingerprint of the secondary structure at the air-water interface was
      reversible. PM-IRRAS was also used to investigate the pH effect of the subphase
      on the secondary structure of OPH. The secondary structure of OPH at the air
      water interface was well defined when the pH of the subphase was near its
      isoelectric point (IP, pH 7.6). However, it adopted a different orientation when
      the subphase pH values were higher or lower than the IP with formation of random
      coil structure. The hydrolysis of organophosphorus compound paraoxon by OPH was
      also studied at the air-water interface by PM-IRRAS. The pH effect and the
      interaction with paraoxon both seem to orientate the enzyme more in the plane of
      the interface and to produce random coil structure.

PMID- 17025357
TI  - Combined rheological and ultrasonic study of alginate and pectin gels near the
      sol-gel transition.
AB  - The sol-gel transition of biopolymer mixtures has been investigated by
      rheological and ultrasonic measurements. A scaling analysis of the data was
      performed for both types of measurements. A gel time was determined from rheology
      for the pure pectin samples, and the data could be fitted to a universal scaling
      form near the transition point. Its critical exponents are in good agreement with
      the predictions of scalar percolation theory. In addition, the ultrasonic signal
      of the pectin samples close to the transition was analyzed in terms of a high
      frequency scaling approach for the attenuation and the velocity. For the alginate
      samples and the mixtures, for which the gel point cannot be determined reliably
      from rheology, the ultrasonic measurements were analyzed using the same scaling
      form as for the pectin sample, thus providing a method for estimating the gel
      point, even in the absence of rheological data.

PMID- 17025358
TI  - Electrohydrodynamic properties of succinoglycan as probed by fluorescence
      correlation spectroscopy, potentiometric titration and capillary electrophoresis.
AB  - The electrostatic, hydrodynamic and conformational properties of aqueous
      solutions of succinoglycan have been analyzed by fluorescence correlation
      spectroscopy (FCS), proton titration, and capillary electrophoresis (CE) over a
      large range of pH values and electrolyte (NaCl) concentrations. Using the
      theoretical formalism developed previously for the electrokinetic properties of
      soft, permeable particles, a quantitative analysis for the electro-hydrodynamics
      of succinoglycan is performed by taking into account, in a self-consistent
      manner, the measured values of the diffusion coefficients, electric charge
      densities, and electrophoretic mobilities. For that purpose, two limiting
      conformations for the polysaccharide in solution are tested, i.e. succinoglycan
      behaves as (i) a spherical, random coil polymer or (ii) a rodlike particle with
      charged lateral chains. The results show that satisfactory modeling of the
      titration data for ionic strengths larger than 50 mM can be accomplished using
      both geometries over the entire range of pH values. Electrophoretic mobilities
      measured for sufficiently large pH values (pH > 5-6) are in line with predictions
      based on either model. The best manner to discriminate between these two
      conceptual models is briefly discussed. For low pH values (pH < 5), both models
      indicate aggregation, resulting in an increase of the hydrodynamic permeability
      and a decrease of the diffusion coefficient.

PMID- 17025359
TI  - Controlling network structure in degradable thiol-acrylate biomaterials to tune
      mass loss behavior.
AB  - Degradable thiol-acrylate materials were synthesized from the mixed-mode
      polymerization of a diacrylate poly(ethylene glycol) (PEG) monomer with thiol
      monomers of varying functionalities to control the final network structure,
      ultimately influencing the material's degradation behavior and properties. The
      influence of the concentration of thiol groups and monomer functionality on the
      mass loss profiles were examined experimentally and theoretically. Mass loss
      behavior was also predicted for networks with varying extents of cyclization, PEG
      molecular weight, and backbone chain length distributions. Experimental results
      indicate that increasing the thiol concentration from 10 to 50 mol % shifted the
      reverse gelation time from 35 to 8 days and the extent of mass loss at reverse
      gelation from 75 to 40%. Similarly, decreasing the thiol functionality from 4 to
      1 shifted the reverse gelation time from 18 to 8 days and the mass loss extent at
      reverse gelation from 70 to 45%.

PMID- 17025360
TI  - Wheat gluten-thiolated poly(vinyl alcohol) blends with improved mechanical
      properties.
AB  - A multifunctional macromolecular thiol (TPVA) obtained by esterification of
      poly(vinyl alcohol) (PVA) with 3-mercaptopropionic acid was characterized by a
      combination of NMR, IR, transmission electron microscopy (TEM), and differential
      scanning calorimetry (DSC), and was used as a wheat gluten (WG) reactive
      modifier. The effect of TPVA molecular weight (M(w) = 2000, 9500, 50 000, and 205
      000) and blend composition (5, 20, and 40% w/w TPVA/WG) on the mechanical
      properties of compression-molded bars indicates that TPVA/WG blends increase the
      fracture strength by up to 76%, the elongation by 80%, and the modulus by 25%
      above WG. In contrast, typical WG additives such as glycerol and sorbitol improve
      flexibility but decrease modulus and strength. Preliminary investigations of
      suspension rheology, water uptake, molecular weight distribution and electron
      microscopy of TPVA/WG and PVA/WG blends illustrate the different protein
      interactions with PVA and TPVA. Further work is underway to determine whether
      TPVA and WG form protein conjugates or microphase-separated morphologies.

PMID- 17025361
TI  - Synthesis and physicochemical and dynamic mechanical properties of a water
      soluble chitosan derivative as a biomaterial.
AB  - The physicochemical and rheological properties of a water-soluble chitosan (WSC)
      derivative were characterized in order to facilitate its use as a novel material
      for biomedical applications. The WSC was prepared by conjugating
      glycidyltrimethylammonium chloride (GTMAC) onto chitosan chains. Varying the
      molar ratio of GTMAC to chitosan from 3:1 to 6:1 produced WSCs with a degree of
      substitution (DS) that ranged from 56% to 74%. The WSC with the highest DS was
      soluble in water up to concentrations of 25 g/dL at room temperature. An increase
      in the polymer concentration gradually increased both the pH and conductivity of
      the WSC solutions. The rheological properties of the WSC solutions were found to
      be dependent on the salt and polymer concentrations as well as the DS value. In
      the absence of salt, the rheological behavior of the WSC was found to be typical
      of that for a polyelectrolyte in the dilute solution regime. However, the
      addition of salt decreased the viscosity of the polymer solution due to the
      reduction of electrostatic repulsions by the positively charged trimethylated
      ammonium groups of the WSC. In the concentrated regime, the viscosity of the WSCs
      was found to follow a power-law expression. The lowest DS WSC had the more
      favorable viscoelastic properties that were attributed to its high molecular
      weight, as confirmed by the stress relaxation spectra and intrinsic viscosity
      measurements. The effect of DS on the degree of interaction between WSC and the
      lipid egg phosphatidylcholine was investigated by FTIR analysis. Overall, the
      lower DS WSC had enhanced rheological properties and was capable of engaging in
      stronger intermolecular physical interactions.

PMID- 17025362
TI  - Physicochemical and transfection properties of cationic Hydroxyethylcellulose/DNA
      nanoparticles.
AB  - In this study the physicochemical and transfection properties of cationic
      hydroxyethylcellulose/plasmid DNA (pDNA) nanoparticles were investigated and
      compared with the properties of DNA nanoparticles based on polyethylene imine
      (PEI), which is widely investigated as a gene carrier. The two types of cationic
      hydroxyethylcelluloses studied, polyquaternium-4 (PQ-4) and polyquaternium-10 (PQ
      10), are already commonly used in cosmetic and topical drug delivery devices.
      Both PQ-4 and PQ-10 spontaneously interact with pDNA with the formation of
      nanoparticles approximately 200 nm in size. Gel electrophoresis and fluorescence
      dequenching experiments indicated that the interactions between pDNA and the
      cationic celluloses were stronger than those between pDNA and PEI. The cationic
      cellulose/pDNA nanoparticles transfected cells to a much lesser extent than the
      PEI-based pDNA nanoparticles. The low transfection property of the PQ-4/pDNA
      nanoparticles was attributed to their neutrally charged surface, which does not
      allow an optimal binding of PQ-4/pDNA nanoparticles to cellular membranes.
      Although the PQ-10/pDNA nanoparticles were positively charged and thus expected
      to be taken up by cells, they were also much less efficient in transfecting cells
      than were PEI/pDNA nanoparticles. Agents known to enhance the endosomal escape
      were not able to improve the transfection properties of PQ-10/pDNA nanoparticles,
      indicating that a poor endosomal escape is, most likely, not the major reason for
      the low transfection activity of PQ-10/pDNA nanoparticles. We hypothesized that
      the strong binding of pDNA to PQ-10 prohibits the release of pDNA from PQ-10 once
      the PQ-10/pDNA nanoparticles arrive in the cytosol of the cells. Tailoring the
      nature and extent of the cationic side chains on this type of cationic
      hydroxyethylcellulose may be promising to further enhance their DNA delivery
      properties.

PMID- 17025363
TI  - Synthesis, characterization, and gene transfer application of poly(ethylene
      glycol-b-ethylenimine) with high molar mass polyamine block.
AB  - The study of ethyloxazoline/methyloxazoline (EtOXZ/MeOXZ) copolymerization,
      initiated by methyl tosylate (MeOTs), showed that (i) incorporation of MeOXZ
      units into random copolymer becomes effective over DP = 100 and (ii) propagation
      process proceeds with negligible transfer to monomer up to a DP of 400 despite
      the presence of MeOXZ in the polymerization medium. These results produced random
      poly(EtOXZ-co-MeOXZ) copolymers with various molar composition ratios in
      alkyloxazoline units. The close values found for the comonomer reactivity ratios
      in acetonitrile (r(1MeOXZ) = 1.18; r(2EtOXZ) = 0.34) implied a random chain
      organization in short sequences of each repeating unit, which was an important
      parameter in view of the optimization of their subsequent modification: the
      alkaline hydrolysis was successfully achieved when the MeOXZ unit content of the
      polyoxazoline chains reached 75%. Using these results, the diblock copolymer
      poly(ethylene glycol-b-(ethyloxazoline-co-methyloxazoline)) (poly(EG-b-(EtOXZ-co
      MeOXZ))) with high DP was synthesized by cationic copolymerization of EtOXZ/MeOXZ
      comonomers using CH(3)-PEG(2kDa)-Ts as macroinitiator. The comonomer composition
      of this new compound was adjusted in order to optimize the hydrolysis step and
      obtain finally the diblock copolymer poly(ethylene glycol-b-ethylenimine)
      (poly(EG-b-EI)). The high molar mass of this copolymer was confirmed both by (1)H
      NMR and SANS measurements. Gene delivery experiments showed that the copolymer
      has significant DNA transfection capacities.

PMID- 17025364
TI  - Thermogelling poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) disulfide
      multiblock copolymer as a thiol-sensitive degradable polymer.
AB  - We report a reverse thermogelling poly(ethylene oxide-b-propylene oxide-b
      ethylene oxide) disulfide multiblock copolymer as a thiol-sensitive biodegradable
      polymer. The poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) aqueous
      solutions studied in this research underwent sol-gel-sol or sol-gel-sol-gel
      transition depending on the molecular weight and concentration of the polymer,
      whereas the corresponding disulfide multiblock copolymer aqueous solutions
      underwent sol-gel transition as the temperature increased in a range of 0-60
      degrees C. The hydrophobic dye solubilization and dynamic light scattering of the
      polymer aqueous solution suggest that the poly(ethylene oxide-b-propylene oxide-b
      ethylene oxide)s undergo unimer (3 nm) to micelle (12 nm) transition, whereas the
      disulfide multiblock copolymers undergo unimer (6 nm) to aggregated polymer (600
      nm) transition as the temperature increases. The gel duration increased from 6 h
      (poly(ethylene oxide-b-propylene oxide-b-ethylene oxide)) to more than 12 days
      (the corresponding disulfide multiblock copolymer) in phosphate buffer saline,
      and the gel duration of the latter depended on the glutathione concentration of
      the medium. The model drug, paclitaxel, was released from the in-situ-formed
      poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) disulfide multiblock
      copolymer gel in a glutathione concentration-sensitive manner.

PMID- 17025365
TI  - Esterification of beta-chitin via intercalation by carboxylic anhydrides.
AB  - beta-chitin is known to form intercalation complexes with aliphatic alcohols and
      amines. We found that it also forms complexes with carboxylic anhydrides. When
      the beta-chitin-acetic anhydride complex was heated to 105 degrees C, the
      hydroxyl groups of chitin were acetylated by a host-guest reaction, maintaining
      the host's crystal structure. Structures of complex and acetylated products were
      analyzed by X-ray diffraction, (13)C CP/MAS NMR, and infrared spectroscopy. The
      maximum degree of substitution (DS) was close to 1.0, suggesting regioselective
      esterification at the C6 position of chitin. Partially acetylated beta-chitin
      with a DS of 0.4 could incorporate various guest species that are difficult to be
      incorporated by original beta-chitin. In contrast, beta-chitin acetate with a DS
      of 1 lost the ability to form a complex. Intercalation complexes of beta-chitin
      with cyclic anhydrides (succinic and maleic) also underwent esterification by
      heating, and the products with a DS of approximately 1 dissolved in aqueous
      alkali, apparently as the result of the dissociation of introduced carboxyl
      groups. These phenomena are potentially useful in controlling the complexation
      ability of beta-chitin and the preparation of regioselectively esterified chitin
      derivatives.

PMID- 17025366
TI  - Glycated polyelectrolyte multilayer films: differential adhesion of primary
      versus tumor cells.
AB  - Glycated polymers have already been widely employed for cell transfection
      studies, as cells possess specific lectins. However, up to now, these glycated
      polymers have barely been investigated for their cell adhesive properties, save
      macrophages. In this work, we use polyelectrolyte multilayer films made of poly(L
      lysine) and poly(L-glutamic) acid as polymeric substrates to investigate the role
      of sugar molecules (e.g., mannose and lactose) on the adhesion of primary cells
      as compared to that of a tumor cell line. The glycated polymeric films were
      compared to ungrafted and chemically cross-linked films, which are known to
      present opposite adhesive properties. A differential adhesion could be evidenced
      on mannose grafted films: primary chondrocytes adhere and proliferate well on
      these films, whereas chondrosarcoma cells do not grow well. Although present, the
      effect of lactose on cell adhesion was much less important. This adhesion,
      mediated by glycated polymers, appears to be specific. These results show that it
      is possible to use glycated polyelectrolytes not only as nonviral vectors but
      also as cell adhesive substrates.

PMID- 17025367
TI  - Macromolecular assemblies based on coupled inclusion complex and electrostatic
      interactions.
AB  - Macromolecular assemblies are elaborated by mixing beta-cyclodextrin-containing
      polymer (polybetaCD), dextran sulfate polyanion (NaDxS), and cationic amphiphiles
      which are adamantane derivatives (Ada1 or Ada2) in aqueous medium. These
      components are assembled via coupled inclusion complex interactions (adamantyl
      group with cyclodextrin cavity) and electrostatic attractive interactions
      (positive charges of Ada with negative charge of NaDxS). The structural
      properties are studied by viscometry and small angle neutron scattering. Ternary
      aggregates with larger size and lower compacities are observed as the cation
      concentration is increased, until phase separation occurs. The results are in
      good agreement with a core-shell association mechanism, the core being made of
      one polybetaCD chain, the shell of NaDxS chains, and the Ada amphiphiles being
      distributed more or less homogeneously inside the cyclodextrin cavities. The
      nature of the Ada counterions has a strong influence on the association as Ada1
      with I(-) counterions give smaller and less compact aggregates than Ada2 with Br(
      ) counterions.

PMID- 17025368
TI  - Ultrastructure of insect and spider cocoon silks.
AB  - Despite much interest in the extraordinary mechanical properties of silks, the
      structure of native silk fibers is still not fully understood. In the present
      study, the morphology, topography, and organization of insect and spider cocoon
      silks were investigated using a range of imaging methods. Field emission scanning
      electron microscopy was used to observe transverse and longitude structures in
      silk fibers subjected to tensile fracturing, freeze fracturing, or polishing. In
      addition, ultrathin sections of silk brins embedded in resin were examined using
      transmission electron microscopy. Finally, dry silk brins were examined by
      confocal microscopy. The results confirmed the existence of well-oriented bundles
      of nanofibrils in all the silks examined and gave an indication of a hierarchical
      construction of the brin. Observed separation of the microfibrils in fractured
      brins suggests that the multifibrillar structure of the silk fiber contributes to
      toughness by allowing dissipation of energy in the controlled propagation of
      cracks.

PMID- 17025369
TI  - NMR, cloud-point measurements and enzymatic depolymerization: complementary tools
      to investigate substituent patterns in modified celluloses.
AB  - The substituent patterns of some chemically modified celluloses were
      characterized as a function of their size distribution, using size-exclusion
      chromatography coupled to both nuclear magnetic resonance spectroscopy (NMR) and
      cloud-point measurements. Intact and enzymatically hydrolyzed methyl cellulose
      (MC) was fractionated according to size, and the level of substitution of the
      fractions was measured off-line using NMR. Clouding behavior was also measured as
      a function of size. Clear differences between hydrolyzed and nonhydrolyzed
      samples were observed using both techniques. For samples that had been
      selectively hydrolyzed using cellulose-degrading enzymes, NMR data showed a
      direct link between the degree of degradation and the level of substitution.
      Differences in the clouding behavior highlighted changes in substituent levels
      and substituent patterns across the size distribution. The techniques gave
      valuable and somewhat complementary information on the substituent distributions
      of the samples before and after enzymatic hydrolysis.

PMID- 17025370
TI  - 1H NMR investigation of thermally triggered insulin release from poly(N
      isopropylacrylamide) microgels.
AB  - We describe investigations of insulin release from thermoresponsive microgels
      using variable temperature (1)H NMR. Microgel particles composed of poly(N
      isopropylacrylamide) were loaded with the peptide via a swelling technique, and
      this method was compared to simple equilibrium partitioning. Variable temperature
      (1)H NMR studies suggest that the swelling loading method results in enhanced
      entrapment of the peptide versus equilibrium partitioning. A centrifugation
      loading assay supports this finding. Pseudo-temperature jump (1)H NMR
      measurements suggest that the insulin release rate is partially decoupled from
      microgel collapse. These types of direct release investigations could prove to be
      useful methods in the future design of controlled macromolecule drug delivery
      devices.

PMID- 17025371
TI  - Phase-transition thermodynamics of N-isopropylacrylamide hydrogels.

PMID- 17025372
TI  - Peptide-based viscoelastic matrices for drug delivery and tissue repair.
AB  - Molecular self-assembly has paved the way to create novel, supramolecular,
      functional biomaterials. Peptide-based biomaterials are gaining interest as a
      result of their programmability, biodegradability, and bioresorbability. Further,
      unlike polymeric materials, peptides can be made monodisperse with precise
      control over sequence, chain length, and stereochemistry. Peptide-based
      viscoelastic matrices have been designed and characterized for various biomedical
      applications, such as tissue engineering scaffolds or drug delivery vehicles. The
      'holy grail' in designing an ideal tissue engineering scaffold lies in mimicking
      the cues of the tissue's natural extracellular matrix (ECM). Some of the key
      elements of ECM that are incorporated into these peptide scaffolds include cell
      adhesive and protease-sensitive sequences for enhanced cell-cell and cell
      biomaterial interactions. Peptide-based viscoelastic matrices can also be
      engineered with drug carrying protease-sensitive sequences for controlled and
      site-specific drug delivery. Molecular-level engineering of simple oligopeptide
      modules can be used to control the position and density of the bio-mimetic
      functionalities in the supramolecular structures, which demonstrates the power of
      the 'bottom-up' approach in self-assembly.

PMID- 17025373
TI  - The pro-oxidant activity of high-dose vitamin E supplements in vivo.
AB  - BACKGROUND: A recent meta-analysis has demonstrated that the regular
      administration of high-dose vitamin E supplements may be associated with
      increased mortality. The biological mechanism for this effect is uncertain.
      METHODS: A ferrous oxidation xylenol assay was used to assess plasma oxidation
      activity levels in samples from a randomized, placebo-controlled, 6-week trial of
      daily vitamin E supplementation in adults with asthma (n = 72). RESULTS AND
      CONCLUSION: A 27% increase in plasma oxidation activity levels was observed in
      patients receiving vitamin E. We demonstrate a pro-oxidant effect of high-dose
      vitamin E supplementation that may explain the increase in mortality observed in
      intervention studies using this nutrient.

PMID- 17025374
TI  - Recombinant omega-conotoxin MVIIA possesses strong analgesic activity.
AB  - BACKGROUND: omega-Conotoxin (CTX) MVIIA is a specific antagonist of N-type
      voltage-sensitive calcium channels. A synthetic peptide version of CTX MVIIA
      (ziconotide) has been approved by the US FDA for severe and chronic pain. Given
      the high cost and complexity of the synthetic process of the disulfide-rich
      peptide, the genetic recombinant approach may simplify the development of this
      potent therapeutic agent. AIM: In this study, we report a new method for
      production of the recombinant CTX MVIIA. METHOD: A novel DNA fragment encoding
      CTX MVIIA was designed using Escherichia coli-preferred codons, and the fragment
      was cloned into the expression vector pGEX(2T). The fusion protein, CTX MVIIA and
      glutathione-S-transferase (GST) [GST-CTX MVIIA], was expressed in E. coli and
      purified by affinity chromatography on a glutathione-agarose column. After
      digestion with thrombin, the CTX MVIIA fragment was purified on a Sephacryl S-100
      HR column and identified by mass spectrometry. The bioactivity of the peptide was
      evaluated by the hot tail-flick assay, in which the CTX MVIIA was
      intracerebroventricularly administered into Sprague-Dawley rats and its
      antinociceptive effect measured. RESULTS: The analgesic activity of the conotoxin
      was about 800 times stronger than that of morphine. CONCLUSION: The recombinant
      CTX MVIIA expressed in E. coli has shown marked analgesic activity, which may
      have potential in clinical application.

PMID- 17025375
TI  - A supramolecular complex between proteinases and beta-cyclodextrin that preserves
      enzymatic activity: physicochemical characterization.
AB  - BACKGROUND: Cyclodextrins are suitable drug delivery systems because of their
      ability to subtly modify the physical, chemical, and biological properties of
      guest molecules through labile interactions by formation of inclusion and/or
      association complexes. Plant cysteine proteinases from Caricaceae and
      Bromeliaceae are the subject of therapeutic interest, because of their anti
      inflammatory, antitumoral, immunogenic, and wound-healing properties. METHODS: In
      this study, we analyzed the association between beta-cyclodextrin (betaCD) and
      fraction P1G10 containing the bioactive proteinases from Carica candamarcensis,
      and described the physicochemical nature of the solid-state self-assembled
      complexes by Fourier transform infrared (FTIR) spectroscopy, thermogravimetry
      (TG), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD),
      and nuclear magnetic resonance (NMR), as well as in solution by circular
      dichroism (CD), isothermal titration calorimetry (ITC), and amidase activity.
      RESULTS AND DISCUSSION: The physicochemical analyses suggest the formation of a
      complex between P1G10 and betaCD. Higher secondary interactions, namely
      hydrophobic interactions, hydrogen bonding and van der Waals forces were observed
      at higher P1G10 : betaCD mass ratios. These results provide evidence of the
      occurrence of strong solid-state supramolecular non-covalent interactions between
      P1G10 and betaCD. Microcalorimetric analysis demonstrates that complexation
      results in a favorable enthalpic contribution, as has already been described
      during formation of similar betaCD inclusion compounds. The amidase activity of
      the complex shows that the enzyme activity is not readily available at 24 hours
      after dissolution of the complex in aqueous buffer; the proteinase becomes
      biologically active by the second day and remains stable until day 16, when a
      gradual decrease occurs, with basal activity attained by day 29. CONCLUSION: The
      reported results underscore the potential for betaCDs as candidates for
      complexing cysteine proteinases, resulting in supramolecular arrays with
      sustained proteolytic activity.

PMID- 17025376
TI  - Adalimumab: a review of its use in adult patients with rheumatoid arthritis.
AB  - Adalimumab (Humira) is a recombinant, fully human anti-tumor necrosis factor
      (TNF) monoclonal antibody approved in the US and Europe for the treatment of
      adult patients with moderate to severe, active rheumatoid arthritis (RA). In
      combination with methotrexate or standard antirheumatic therapy or as
      monotherapy, adalimumab effectively reduced signs and symptoms of RA, induced
      remission, improved physical function and inhibited the progression of structural
      damage in several randomized, double-blind, placebo-controlled phase III trials.
      The drug was generally well tolerated, with most adverse events being mild to
      moderate, and the serious adverse events profile being similar to that generally
      seen in patients with RA not receiving anti-TNF agents. Adalimumab was at least
      as cost effective as other anti-TNF agents used in the therapy of RA, and
      provided significant improvements in patients' health-related quality of life.
      Overall, adalimumab in combination with methotrexate or standard antirheumatic
      therapy is valuable as a first-line therapeutic option in patients with early,
      aggressive RA, and a second-line therapeutic option in patients with long
      standing, moderate to severe RA. For the latter indication, adalimumab may also
      be used as monotherapy.

PMID- 17025377
TI  - Human papillomavirus quadrivalent (types 6, 11, 16, 18) recombinant vaccine
      (Gardasil): profile report.

PMID- 17025378
TI  - Hexyl aminolevulinate in the detection of bladder cancer: profile report.

PMID- 17025379
TI  - Spotlight on darbepoetin alfa in the treatment of anemia in patients with cancer
      receiving chemotherapy.
AB  - Darbepoetin alfa (Aranesp) is an analog of recombinant human erythropoietin
      (rHuEPO) produced using recombinant DNA technology. The high number of sialic
      acid moieties in darbepoetin alfa results in a prolonged half-life and enhanced
      in vivo biologic activity compared with rHuEPO (as demonstrated in animal
      studies), and permits a reduction in the frequency of administration.
      Subcutaneous darbepoetin alfa 2.25 microg/kg once weekly or 500microg once every
      3 weeks (with a provision for dosage adjustments) is an effective and well
      tolerated erythropoietic agent in anemic patients with cancer receiving
      chemotherapy. In randomized, controlled clinical trials, the drug increased
      hemoglobin levels and reduced the need for blood transfusions in patients with
      various types of nonmyeloid malignancies, and also ameliorated anemia-related
      fatigue, thereby improving their health-related quality of life scores. The once
      every-3-weeks dosage regimen provides further convenience by offering the
      possibility of synchronizing its administration with most chemotherapy regimens.
      Direct comparisons between approved dosages of darbepoetin alfa and other
      erythropoietic agents have not been conducted. Such comparisons would be very
      helpful in formulating definitive conclusions about their relative efficacy and
      cost effectiveness. Darbepoetin alfa provides an effective and well tolerated
      treatment option for the treatment of anemia in patients with cancer receiving
      chemotherapy.

PMID- 17025380
TI  - Universal amplitude ratio Gamma-/Gamma+ for two-dimensional percolation.
AB  - The amplitude ratio of the susceptibility (or second size moment) for two
      dimensional percolation is calculated by two series methods and also by Monte
      Carlo simulation. The first series method is an approach based upon integrating
      approximations to the scaling function. The second series method directly uses
      low- and high-density series expansions of the susceptibility, going to
      unprecedented orders for both bond and site percolation on the square lattice.
      Putting all methods together we find a consistent value Gamma-/Gamma+ = 162.5+/-2
      , a significant improvement over previous results that placed the value of this
      ratio variously in the range of 14 to 220.

PMID- 17025381
TI  - Two-dimensional intermittent search processes: An alternative to Levy flight
      strategies.
AB  - Levy flights are known to be optimal search strategies in the particular case of
      revisitable targets. In the relevant situation of nonrevisitable targets, we
      propose an alternative model of two-dimensional (2D) search processes, which
      explicitly relies on the widely observed intermittent behavior of foraging
      animals. We show analytically that intermittent strategies can minimize the
      search time, and therefore do constitute real optimal strategies. We study two
      representative modes of target detection and determine which features of the
      search time are robust and do not depend on the specific characteristics of
      detection mechanisms. In particular, both modes lead to a global minimum of the
      search time as a function of the typical times spent in each state, for the same
      optimal duration of the ballistic phase. This last quantity could be a universal
      feature of 2D intermittent search strategies.

PMID- 17025382
TI  - Activation through a narrow opening.
AB  - The escape of Brownian motion through a narrow absorbing window in an otherwise
      reflecting boundary of a domain is a rare event. In the presence of a deep
      potential well, there are two long time scales, the mean escape time from the
      well and the mean time to reach the absorbing window. We derive a generalized
      Kramers formula for the mean escape time through the narrow window.

PMID- 17025383
TI  - Pfaffian solution of a dimer-monomer problem: Single monomer on the boundary.
AB  - We consider the dimer-monomer problem for the rectangular lattice. By mapping the
      problem into one of close-packed dimers on an extended lattice, we rederive the
      Tzeng-Wu solution for a single monomer on the boundary by evaluating a Pfaffian.
      We also clarify the mathematical content of the Tzeng-Wu solution by identifying
      it as the product of the nonzero eigenvalues of the Kasteleyn matrix.

PMID- 17025384
TI  - One-way coupling enables noise-mediated spatiotemporal patterns in media of
      otherwise quiescent multistable elements.
AB  - Recent work has demonstrated that undriven and overdamped bistable systems, which
      are normally quiescent, can oscillate if unidirectionally coupled into arrays
      with cyclic boundary conditions. Here, we understand such oscillations as
      corresponding to the propagation of solitonlike waves. Further, in large arrays,
      we demonstrate how noise and coupling, together, mediate the resulting complex
      spatiotemporal dynamics.

PMID- 17025385
TI  - Solvophobic solvation at large and intermediate length scales: Size, shape, and
      solvent effects.
AB  - We report the results of molecular-dynamics simulations of solvophobic
      nanoparticles in n -decane solvent. We observe that solvent ordering in the
      interparticle gap and solvation forces depend on the particle size and shape.
      Analogous to hydrophobic hydration, we observe dewetting of the interparticle
      region when the nanoparticle separation becomes smaller than a critical value of
      delta(c). We observe that delta(c) exhibits a nonmonotonic dependence on
      nanoparticle size, in contrast to what is expected from studies of water. While
      studies of hydrophobic hydration indicate that two solute length scales govern
      hydrophobic interactions, our studies indicate that a third length scale can be
      important in the more general phenomenon of solvophobic solvation.

PMID- 17025386
TI  - Small-angle x-ray scattering study of flow alignment of a thermotropic liquid
      crystal in the nematic and smectic phases.
AB  - The capillary flow alignment of the thermotropic liquid crystal 4-n-octyl-4'
      cyanobiphenyl in the nematic and smectic phases is investigated using time
      resolved synchrotron small-angle x-ray scattering. Samples were cooled from the
      isotropic phase to erase prior orientation. Upon cooling through the nematic
      phase under Poiseuille flow in a circular capillary, a transition from the
      alignment of mesogens along the flow direction to the alignment of layers along
      the flow direction (mesogens perpendicular to flow) appears to occur continuously
      at the cooling rate applied. The transition is centered on a temperature at which
      the Leslie viscosity coefficient alpha3 changes sign. The configuration with
      layers aligned along the flow direction is also observed in the smectic phase.
      The transition in the nematic phase on cooling has previously been ascribed to an
      aligning-nonaligning or tumbling transition. At high flow rates there is evidence
      for tumbling around an average alignment of layers along the flow direction. At
      lower flow rates this orientation is more clearly defined. The layer alignment is
      ascribed to surface-induced ordering propagating into the bulk of the capillary,
      an observation supported by the parallel alignment of layers observed for a
      static sample at low temperatures in the nematic phase.

PMID- 17025387
TI  - Colored-noise-induced Hopf bifurcations in predator-prey communities.
AB  - A broad class of (N+1) -species ratio-dependent predator-prey stochastic models,
      which consist of one predator population and N prey populations, is considered.
      The effect of a fluctuating environment on the carrying capacities of prey
      populations is taken into account as colored noise. In the framework of the mean
      field theory, approximate self-consistency equations for prey-populations mean
      density and for predator-population density are derived (to the first order in
      the noise variance). In some cases, the mean field exhibits Hopf bifurcations as
      a function of noise correlation time. The corresponding transitions are found to
      be reentrant, e.g., the periodic orbit appears above a critical value of the
      noise correlation time, but disappears again at a higher value of the noise
      correlation time. The nonmonotonous dependence of the critical control parameter
      on the noise correlation time is found, and the conditions for the occurrence of
      Hopf bifurcations are presented. Our results provide a possible scenario for
      environmental-fluctuations-induced transitions between the oscillatory regime and
      equilibrium state of population sizes observed in nature.

PMID- 17025388
TI  - Optimal response function in networks of excitatory elements.
AB  - In this paper the problem of signal propagation in networks of excitatory
      elements is studied. It is found that the geometry of signal transmission paths
      depends crucially on how an excitatory element responds to a stimulus. Two types
      of responses are defined: fast and slow. In the slow response case the signal
      transmission paths are in the same universality class as optimal paths in the
      limit of strong disorder. The signal transmission paths formed in the fast
      response case constitute possibly a new universality class.

PMID- 17025389
TI  - Diffusion equations for a Markovian jumping process.
AB  - We consider a Markovian jumping process which is defined in terms of the jump
      size distribution and the waiting-time distribution with a position-dependent
      frequency, in the diffusion limit. We assume the power-law form for the
      frequency. For small steps, we derive the Fokker-Planck equation and show the
      presence of the normal diffusion, subdiffusion, and superdiffusion. For the Levy
      distribution of the step size, we construct a fractional equation, which
      possesses a variable coefficient, and solve it in the diffusion limit. Then we
      calculate fractional moments and define the fractional diffusion coefficient as a
      natural extension to the cases with the divergent variance. We also solve the
      master equation numerically and demonstrate that there are deviations from the
      Levy stable distribution for large wave numbers.

PMID- 17025391
TI  - Off-diagonal correlations of the Calogero-Sutherland model.
AB  - We study correlation functions of the Calogero-Sutherland model in the whole
      range of the interaction parameter. Using the replica method we obtain analytical
      expressions for the long-distance asymptotics of the one-body density matrix in
      addition to the previously derived asymptotics of the pair-distribution function
      [D.M. Gangardt and A. Kamenev, Nucl. Phys. B 610, 578 (2001)]. The leading
      analytic and nonanalytic terms in the short-distance expansion of the one-body
      density matrix are discussed. Numerical results for these correlation functions
      are obtained using Monte Carlo techniques for all distances. The momentum
      distribution and static structure factor are calculated. The potential and
      kinetic energies are obtained using the Hellmann-Feynman theorem. Perfect
      agreement is found between the analytical expressions and numerical data. These
      results allow for the description of physical regimes of the Calogero-Sutherland
      model. The zero temperature phase diagram is found to be of a crossover type and
      includes quasicondensation, quasicrystallization and quasisupersolid regimes.

PMID- 17025390
TI  - Phase diagram and commensurate-incommensurate transitions in the phase field
      crystal model with an external pinning potential.
AB  - We study the phase diagram and the commensurate-incommensurate transitions in a
      phase field model of a two-dimensional crystal lattice in the presence of an
      external pinning potential. The model allows for both elastic and plastic
      deformations and provides a continuum description of lattice systems, such as for
      adsorbed atomic layers or two-dimensional vortex lattices. Analytically, a mode
      expansion analysis is used to determine the ground states and the commensurate
      incommensurate transitions in the model as a function of the strength of the
      pinning potential and the lattice mismatch parameter. Numerical minimization of
      the corresponding free energy shows reasonable agreement with the analytical
      predictions and provides details on the topological defects in the transition
      region. We find that for small mismatch the transition is of first order, and it
      remains so for the largest values of mismatch studied here. Our results are
      consistent with results of simulations for atomistic models of adsorbed
      overlayers.

PMID- 17025392
TI  - Phase transitions in highly asymmetric binary hard-sphere fluids: Fluid-fluid
      binodal from a two-component mixture theory.
AB  - Fluid-fluid binodals of binary hard-sphere mixtures are computed from the
      recently proposed fundamental measure functional-mean spherical approximation
      closure of the two-component Ornstein-Zernike equation. The results, especially
      in the dense fluid region that was not accessible by previous theoretical
      methods, are compared with the corresponding ones for the one-component fluid of
      big spheres with effective potential obtained from the same closure. The general
      trends are those expected for hard-sphere potentials but small difference are
      detectable. The overall agreement found validates the equivalence of the two
      descriptions for size ratios R = 8.5 or greater.

PMID- 17025393
TI  - Evolutionary prisoner's dilemma game with dynamic preferential selection.
AB  - We study a modified prisoner's dilemma game taking place on two-dimensional
      disordered square lattices. The players are pure strategists and can either
      cooperate or defect with their immediate neighbors. In the generations each
      player updates its strategy by following one of the neighboring strategies with a
      probability dependent on the payoff difference. The neighbor selection obeys a
      dynamic preferential rule, i.e., the more frequently a neighbor's strategy was
      adopted by the focal player in the previous rounds, the larger probability it
      will be chosen to refer to in the subsequent rounds. It is found that cooperation
      is substantially promoted due to this simple selection mechanism. Corresponding
      analysis is provided by the investigation of the distribution of the players'
      impact weights, persistence, and correlation function.

PMID- 17025394
TI  - Dynamical origin of memory and renewal.
AB  - We show that the dynamic approach to fractional Brownian motion (FBM) establishes
      a link between a non-Poisson renewal process with abrupt jumps resetting to zero
      the system's memory and correlated dynamic processes, whose individual
      trajectories keep a nonvanishing memory of their past time evolution. It is well
      known that the recrossings of the origin by an ordinary one-dimensional diffusion
      trajectory generates a Levy (and thus renewal) process of index theta = 1/2 . We
      prove with theoretical and numerical arguments that this is the special case of a
      more general condition, insofar as the recrossings produced by the dynamic FBM
      generates a Levy process with 0 < theta < 1. This result is extended to produce a
      satisfactory model for the fluorescent signal of blinking quantum dots.

PMID- 17025395
TI  - Continuously varying exponents in A+B-->0 reaction with long-ranged attractive
      interaction.
AB  - We investigate kinetics of A+B-->0 reaction with long-range attractive
      interaction V(r) approximately -r(-2sigma) between A and B or with drift velocity
      v approximately r(-sigma) in one dimension, where r is the closest distance
      between A and B . It is analytically shown that dynamical exponents for density
      of particles (rho) and size of domains (l) continuously vary with sigma when
      sigma < sigma(c) = 1/2 , while that for the distance between adjacent opposite
      species (l(AB)) varies when sigma < sigma(c)AB = 7/6 . For sigma > sigma(c)AB
      diffusive motions dominate the kinetics. These anomalous behaviors with the two
      crossover values of sigma are supported by numerical simulations.

PMID- 17025396
TI  - Force distribution in a randomly perturbed lattice of identical particles with
      1/r2 pair interaction.
AB  - We study the statistics of the force felt by a particle in the class of a
      spatially correlated distribution of identical pointlike particles, interacting
      via a 1/r2 pair force (i.e., gravitational or Coulomb), and obtained by randomly
      perturbing an infinite perfect lattice. We specify the conditions under which the
      force on a particle is a well-defined stochastic quantity. We then study the
      small displacements approximation, giving both the limitations of its validity
      and, when it is valid, an expression for the force variance. The method
      introduced by Chandrasekhar to find the force probability density function for
      the homogeneous Poisson particle distribution is extended to shuffled lattices of
      particles. In this way, we can derive an approximate expression for the
      probability distribution of the force over the full range of perturbations of the
      lattice, i.e., from very small (compared to the lattice spacing) to very large
      where the Poisson limit is recovered. We show in particular the qualitative
      change in the large-force tail of the force distribution between these two
      limits. Excellent accuracy of our analytic results is found on detailed
      comparison with results from numerical simulations. These results provide basic
      statistical information about the fluctuations of the interactions (i) of the
      masses in self-gravitating systems like those encountered in the context of
      cosmological N -body simulations, and (ii) of the charges in the ordered phase of
      the one-component plasma, the so-called Coulomb or Wigner crystal.

PMID- 17025397
TI  - Fluctuation symmetries for work and heat.
AB  - We consider a particle dragged through a medium at constant temperature as
      described by a Langevin equation with a time-dependent potential. The time
      dependence is specified by an external protocol. We give conditions on potential
      and protocol under which the fluctuations of the dissipative work satisfy an
      exact symmetry for all times. We also present counterexamples to that fluctuation
      theorem when our conditions are not satisfied. Finally, we consider the
      dissipated heat, which differs from the work by a temporal boundary term. We
      explain why there is a correction to the standard fluctuation theorem due to the
      unboundedness of that temporal boundary. However, the corrected fluctuation
      relation has again a general validity.

PMID- 17025398
TI  - Flux reversal in a simple random-walk model on a fluctuating symmetric lattice.
AB  - A rather simple random-walk model on a one-dimensional lattice is put forward.
      The lattice as a whole switches randomly between two possible states which are
      spatially symmetric. Both lattice states are identical, but translated by one
      site with respect to each other, and consist of infinite arrays of absorbing
      sites separated by two nonabsorbing sites. Exact explicit expressions for the
      long-time velocity and the effective diffusion coefficient are obtained and
      discussed. In particular, it is shown that the direction of the steady motion can
      be reversed by conveniently varying the values of either the mean residence times
      in the lattice states or the transition rates to the absorbing and nonabsorbing
      sites.

PMID- 17025399
TI  - Mean crossover functions for uniaxial three-dimensional Ising-like systems.
AB  - We give simple expressions for the mean of the max and min bounds of the critical
      to-classical crossover functions, previously calculated [Bagnuls and Bervillier,
      Phys. Rev. E 65, 066132 (2002)] within the massive renormalization scheme of the
      Phi(d)4(n) model in three dimensions (d = 3) and scalar order parameter (n = 1)
      of the Ising-like universality class. The mean functions are determined relying
      on the properties of the theoretical functions in the two limiting three
      dimensional (3D) Ising-like and mean-field-like descriptions close to the Wilson
      Fisher fixed point and to the Gaussian fixed point, respectively. Such
      descriptions correspond to the preasymptotic domains near each fixed point where
      a Wegner expansion restricted to two terms (leading and first confluent terms) is
      valid. The Ising-like preasymptotic domain description includes the correlations
      between parameters due to the error-bar determination of the exponents and
      amplitude combinations very close to the Wilson-Fisher fixed point. Adding the
      equivalent description of the mean field preasymptotic domain close to the
      Gaussian fixed point leads to define each mean crossover function with three
      calculated parameters. Fixing a unique value of one parameter whatever the
      selected mean crossover function, we use this parameter as a relative sensor to
      estimate the dominant nature, either (Ising-like) critical, or (mean-field-like)
      classical, of the crossover behavior. Finally, we obtain an explicit criterion to
      measure the extension of the Ising-like preasymptotic domain which can then
      permit to coherently account for measurements performed in systems where the
      asymptotical approach to the critical point remains finite, using a well
      controlled number of system-dependent parameters (like in the subclass of one
      component fluids).

PMID- 17025400
TI  - Logarithmic corrections to correlation decay in two-dimensional random-bond Ising
      systems.
AB  - The statistics of critical spin-spin correlation functions in Ising systems with
      nonfrustrated disorder are investigated on a strip geometry, via numerical
      transfer-matrix techniques. Conformal invariance concepts are used, in order to
      test for logarithmic corrections to pure power-law decay against distance. Fits
      of our data to conformal-invariance expressions, specific to logarithmic
      corrections to correlations on strips, give results with the correct sign, for
      the moments of order n = 0-4 of the correlation-function distribution. We find an
      interval of disorder strength along which corrections to pure-system behavior can
      be decomposed into the product of a known n -dependent factor and an
      approximately n -independent one, in accordance with predictions. A
      phenomenological fitting procedure is proposed, which takes partial account of
      subdominant terms of correlation-function decay on strips. In the low-disorder
      limit, it gives results in fairly good agreement with theoretical predictions,
      provided that an additional assumption is made.

PMID- 17025401
TI  - Bulk fluorescence measurements cannot probe the survival-time distribution of
      single molecules.
AB  - Using a straightforward theoretical approach, we show that an ensemble of dyes
      with a simple first-order photobleaching kinetics yields a power-law decaying
      emission intensity in a heterogeneous excitation field in bulk fluorescence
      experiments. Our theoretical considerations are experimentally confirmed for two
      distinct classes of small organic fluorophores represented by the classical laser
      dye rhodamine-6G on glass in air and the cyanine dye DiI(C18) in a thin
      polymethylmethacrylate film. Our results provide evidence that the time course of
      bleaching in a bulk sample in general does not allow derivation of the properties
      of survival times of individual quantum systems.

PMID- 17025402
TI  - Drift velocity for a chain of beads in one dimension.
AB  - The one-dimensional motion of a chain of N beads is studied to determine its
      drift velocity when an external field is applied. The dependences of the drift
      velocity with the chain length and field strength are addressed. Two cases are
      considered, chains with all their beads charged and chains having an end bead
      charged. In the last case, an analytical expression for the drift velocity is
      proposed for all N . Results are tested with the help of Monte Carlo simulations.

PMID- 17025403
TI  - Fluctuation theorem for the effusion of an ideal gas.
AB  - The probability distribution of the entropy production for the effusion of an
      ideal gas between two compartments is calculated explicitly. The fluctuation
      theorem is verified. The analytic results are in good agreement with numerical
      data from hard disk molecular dynamics simulations.

PMID- 17025404
TI  - Diffusive anomalies in a long-range Hamiltonian system.
AB  - We scrutinize the anomalies in diffusion observed in an extended long-range
      system of classical rotors, the HMF model. Under suitable preparation, the system
      falls into long-lived quasi-stationary states for which superdiffusion of rotor
      phases has been reported. In the present work, we investigate diffusive motion by
      monitoring the evolution of full distributions of unfolded phases. After a
      transient, numerical histograms can be fitted by the q -Gaussian form P(x)
      proportional to {1+(q-1)[x/beta]2}(1/(1-q)) , with parameter q increasing with
      time before reaching a steady value q approximately 32 (squared Lorentzian). From
      the analysis of the second moment of numerical distributions, we also discuss the
      relaxation to equilibrium and show that diffusive motion in quasistationary
      trajectories depends strongly on system size.

PMID- 17025405
TI  - Diffusion of interacting Brownian particles: Jamming and anomalous diffusion.
AB  - The free self-diffusion of an assembly of interacting particles confined on a
      quasi-one-dimensional ring is investigated both numerically and analytically. The
      interparticle pairwise interaction can be either attractive or repulsive and the
      energy barrier opposing thermal hopping of two particles one past the other is
      finite. Thus, for sufficiently long times, self-diffusion becomes normal or
      conventional diffusion. However, depending on the particle density, subdiffusive
      transients with exponent 12 and suppression of normal diffusion are observed.
      Above a certain density threshold, a sudden drop to zero of the diffusion
      coefficient for attractive particles signals the transition to a jammed phase.
      Furthermore, a Gaussian cluster of attractive particles condenses, by shrinking
      in size, for densities larger than such density threshold; lower density clusters
      spread out, regardless of the interaction sign, through a diffusion mechanism
      that is anomalous at short times, and normal for sufficiently long times. These
      effects could be observed in systems with colloidal particles, vortices,
      electrons, among other interacting particle systems.

PMID- 17025406
TI  - Temporal extensivity of Tsallis' entropy and the bound on entropy production
      rate.
AB  - The Tsallis entropy, which is a generalization of the Boltzmann-Gibbs entropy,
      plays a central role in nonextensive statistical mechanics of complex systems. A
      lot of efforts have recently been made on establishing a dynamical foundation for
      the Tsallis entropy. They are primarily concerned with nonlinear dynamical
      systems at the edge of chaos. Here, it is shown by generalizing a formulation of
      thermostatistics based on time averages recently proposed by Carati [A. Carati,
      Physica A 348, 110 (2005)] that, whenever relevant, the Tsallis entropy indexed
      by q is temporally extensive: linear growth in time, i.e., finite entropy
      production rate. Then, the universal bound on the entropy production rate is
      shown to be 1/ absolute value (1-q). The property of the associated probabilistic
      process, i.e., the sojourn time distribution, determining randomness of motion in
      phase space is also analyzed.

PMID- 17025407
TI  - Properties of non-fcc hard-sphere solids predicted by density functional theory.
AB  - The free energies of the fcc, bcc, hcp, and simple cubic phases for hard spheres
      are calculated as a function of density using the fundamental measure theory
      models of Rosenfeld [Phys. Rev. E 55, 4245 (1997)], Tarazona [Phys. Rev. Lett.
      84, 694 (2001)], and Roth [J. Phys.: Condens. Matter 14, 12063 (2002)] in the
      Gaussian approximation. For the fcc phase, the present work confirms the
      vanishing of the Lindemann parameter (i.e., vanishing of the width of the
      Gaussians) near close packing for all three models and the results for the hcp
      phase are nearly identical. For the bcc phase and for packing fractions above eta
      approximately 0.56 , all three theories show multiple solid structures differing
      in the widths of the Gaussians. In all three cases, one of these structures shows
      the expected vanishing of the Lindemann parameter at close packing, but this
      physical structure is only thermodynamically favored over the unphysical
      structures in the Tarazona theory and even then, some unphysical behavior
      persists at lower densities. The simple cubic phase is stabilized in the model of
      Rosenfeld for a range of densities and in the Tarazona model only very near close
      packing.

PMID- 17025408
TI  - Cooperative dynamics in coupled noisy dynamical systems near a critical point:
      The dc superconducting quantum interference device as a case study.
AB  - Dynamical systems that operate near the onset of coupling-induced oscillations
      can exhibit enhanced sensitivity to external perturbations under suitable
      operating parameters. This cooperative behavior and the attendant enhancement in
      the system response (quantified here via a signal-to-noise ratio at the
      fundamental of the coupling-induced oscillation frequency) are investigated in
      this work. As a prototype, we study an array of dc superconducting quantum
      interference device (SQUID) rings locally coupled, unidirectionally as well as
      bidirectionally, in a ring configuration; it is well known that each individual
      SQUID can be biased through a saddle-node bifurcation to oscillatory behavior. We
      show that biasing the array near the bifurcation point of coupling-induced
      oscillations can lead to a significant performance enhancement.

PMID- 17025409
TI  - Attempt to distinguish long-range temporal correlations from the statistics of
      the increments by natural time analysis.
AB  - Self-similarity may originate from two origins: i.e., the process memory and the
      process' increments "infinite" variance. A distinction is attempted by employing
      the natural time chi . Concerning the first origin, we analyze recent data on
      seismic electric signals, which support the view that they exhibit infinitely
      ranged temporal correlations. Concerning the second, slowly driven systems that
      emit bursts of various energies E obeying the power-law distribution--i.e., P(E)
      approximately E(-gamma)--are studied. An interrelation between the exponent gamma
      and the variance kappa1(identical with <chi2> - <chi2>) is obtained for the
      shuffled (randomized) data. For real earthquake data, the most probable value of
      kappa1 of the shuffled data is found to be approximately equal to that of the
      original data, the difference most likely arising from temporal correlation.
      Finally, it is found that the differential entropy associated with the
      probability P(kappa1) maximizes for gamma around gamma approximately 1.6-1.7 ,
      which is comparable to the value determined experimentally in diverse phenomena:
      e.g., solar flares, icequakes, dislocation glide in stressed single crystals of
      ice, etc. It also agrees with the b value in the Gutenberg-Richter law of
      earthquakes. In addition, the case of multiplicative cascades is studied in the
      natural time domain.

PMID- 17025410
TI  - Strong clustering of noninteracting, sliding passive scalars driven by
      fluctuating surfaces.
AB  - We study the clustering of passive, noninteracting particles moving under the
      influence of a fluctuating field and random noise, in one and two dimensions. The
      fluctuating field in our case is provided by surfaces governed by the Kardar
      Parisi-Zhang (KPZ) and the Edwards-Wilkinson (EW) equations, and the sliding
      particles follow the local surface slope. As the KPZ equation can be mapped to
      the noisy Burgers equation, the problem translates to that of passive scalars in
      a Burgers fluid. Monte Carlo simulations on discrete lattice models reveal very
      strong clustering of the passive particles for all sorts of dynamics under
      consideration. The resulting strong clustering state is defined using the scaling
      properties of the two point density-density correlation function. Our simulations
      show that the state is robust against changing the ratio of update speeds of the
      surface and particles. We also solve the related equilibrium problem of a
      stationary surface and finite noise, well known as the Sinai model for random
      walkers on a random landscape. For this problem, we obtain analytic results which
      allow closed form expressions to be found for the quantities of interest.
      Surprisingly, these results for the equilibrium problem show good agreement with
      the nonequilibrium KPZ problem.

PMID- 17025411
TI  - Molecular dynamics study of the thermodynamics and transport coefficients of hard
      hyperspheres in six and seven dimensions.
AB  - Molecular dynamics (MD) simulations are performed for six- and seven-dimensional
      hard-hypersphere fluids. The equation of state, velocity autocorrelation
      function, self-diffusion coefficient, shear viscosity, and thermal conductivity
      are determined as a function of density. The molecular dynamics results for the
      equation of state are found to be in excellent agreement with values obtained
      from theoretical approaches and previous MD simulations in seven dimensions. The
      short-time behavior of the velocity autocorrelation function is well described by
      the Enskog exponential approximation. The Enskog predictions for the self
      diffusion coefficient and the viscosity agree fairly well with the simulation
      data at low densities, but underestimate these quantities at higher densities.
      Data for the thermal conductivity are in fine agreement with Enskog theory for
      all densities and dimensions studied.

PMID- 17025412
TI  - Influence of two-body and three-body interatomic forces on gas, liquid, and solid
      phases.
AB  - Accurate molecular dynamics simulations are reported which quantify the
      contributions of two- and three-body interactions in the gas, liquid, and solid
      phases of argon at both subcritical and supercritical conditions. The
      calculations use an accurate two-body potential in addition to contributions from
      three-body dispersion interactions from third-order triple-dipole interactions.
      The number dependence of three-body interactions is quantified, indicating that a
      system size of at least five hundred atoms is required for reliable calculations.
      The results indicate that, although the contribution of three-body interaction to
      the overall energy is small, three-body interactions significantly affect the
      pressure at which vapor-liquid and solid-liquid transitions are observed. In
      particular, three-body interactions substantially increase the pressure of the
      freezing point. Unlike two-body interactions, which vary with both density and
      temperature, for a given density, three-body interactions have a near-constant
      'background' value irrespective of the temperature. Both two-body interactions
      and kinetic energy have an important role in vapor-liquid equilibria whereas
      solid-liquid equilibria are dominated by two-body interactions.

PMID- 17025413
TI  - Experimental study of the compaction dynamics for two-dimensional anisotropic
      granular materials.
AB  - We present an experimental study of the compaction dynamics for two-dimensional
      anisotropic granular systems. The compaction dynamics of rods is measured at
      three different scales: (i) the macroscopic scale through the packing fraction
      rho, (ii) the mesoscopic scale through both fractions of aligned grains phi(a)
      and ideally ordered grains phi(io), and (iii) the microscopic scale through both
      rotational and translational grain mobilities mu(r,t). At the macroscopic scale,
      we have observed two stages during the compaction process, suggesting different
      characteristic time scales for grain relaxation. At the mesoscopic scale, we have
      observed the formation and the growth of domains made of aligned grains during
      the first stage of compaction. At the late stage, these domains of aligned grains
      are sheared to form ideally ordered domains. From a microscopic point of view,
      measurements reveal that the beginning of the compaction process is essentially
      related to translational motions of the grains. The grain rotations drive mainly
      the process during the late stages of compaction.

PMID- 17025414
TI  - High viscosity gas fluidization of fine particles: An extended window of
      quasihomogeneous flow.
AB  - We explore the role of gas viscosity in the behavior of gas-fluidized beds of
      fine powders by means of experimental measurements using nitrogen and neon as
      fluidizing gases, and theoretical considerations. The existence of a nonbubbling
      fluidlike regime has been recently observed in beds of fine powders fluidized
      with nitrogen. Our experiments with neon reveal a discontinuous transition from
      heterogeneous fluidization to a highly expanded homogeneous fluidization state.
      We point out that increasing gas viscosity enhances the coherence of agglomerate
      swarms, which promotes a local void-splitting mechanism, thus improving the
      uniformity of fluidization. Our theoretical analysis predicts that further
      increase of gas viscosity would produce a full suppression of the bubbling
      regime, i.e., the uniformly fluidized bed would undergo a direct transition to a
      turbulent regime as seen in beds of nanoparticles fluidized by nitrogen and in
      liquid-fluidized beds of moderate-density beads.

PMID- 17025415
TI  - Identification of arches in two-dimensional granular packings.
AB  - We identify arches in a bed of granular disks generated by a molecular dynamic
      type simulation. We use the history of the deposition of the particles to
      identify the supporting contacts of each particle. Then, arches are defined as
      sets of mutually stable disks. Different packings generated through tapping are
      analyzed. The possibility of identifying arches from the static structure of a
      deposited bed, without any information on the history of the deposition, is
      discussed.

PMID- 17025416
TI  - Formation and transport of a sand heap in an inclined and vertically vibrated
      container.
AB  - We investigate experimentally the formation and the transportation of a heap
      formed by granular materials in an inclined and vertically vibrated container. We
      observe how the transport velocity of heap up the container is related to the
      driving acceleration, the driving frequency, and the inclination of the
      container. An empirical law which governs the transport velocity of the heap is
      presented. An analogous experiment was performed with a heap-shaped Plexiglas
      block. We propose that the compressive force resulted from pressure gradient in
      ambient gas plays a crucial role in enhancing and maintaining a heap, and the
      ratchet effect causes the movement of the heap.

PMID- 17025417
TI  - Drag and lift on rotating vanes in granular beds.
AB  - We have performed systematic experiments on vane intruders of different sizes and
      aspect ratios that are immersed and slowly rotated in beds of monodisperse glass
      beads of different diameters. We find that the torque and lift force on the vane
      increase with bead size. The measured torque on the rotating vanes follows a
      scaling behavior that depends on the effective immersion depth and the effective
      vane diameter. The torque increases with the square of the effective immersion
      depth and the square of the effective vane diameter, and closely resembles the
      scaling behavior previously reported for the torque on rotating cylinders. We
      also find that the vertical lift forces have a supralinear dependence on the
      effective immersion depth, and qualitatively resemble the plunging forces
      produced when an intruder is slowly immersed into beds of glass beads.

PMID- 17025418
TI  - Analysis of granular flow in a pebble-bed nuclear reactor.
AB  - Pebble-bed nuclear reactor technology, which is currently being revived around
      the world, raises fundamental questions about dense granular flow in silos. A
      typical reactor core is composed of graphite fuel pebbles, which drain very
      slowly in a continuous refueling process. Pebble flow is poorly understood and
      not easily accessible to experiments, and yet it has a major impact on reactor
      physics. To address this problem, we perform full-scale, discrete-element
      simulations in realistic geometries, with up to 440,000 frictional, viscoelastic
      6-cm-diam spheres draining in a cylindrical vessel of diameter 3.5m and height 10
      m with bottom funnels angled at 30 degrees or 60 degrees. We also simulate a
      bidisperse core with a dynamic central column of smaller graphite moderator
      pebbles and show that little mixing occurs down to a 1:2 diameter ratio. We
      analyze the mean velocity, diffusion and mixing, local ordering and porosity
      (from Voronoi volumes), the residence-time distribution, and the effects of wall
      friction and discuss implications for reactor design and the basic physics of
      granular flow.

PMID- 17025419
TI  - Nonlinear effects in charge stabilized colloidal suspensions.
AB  - Molecular-dynamics simulations are used to study the effective interactions in
      charged stabilized colloidal suspensions. We focus on highly charged macroions in
      the limit of low salt concentrations. Within this regime, nonlinear corrections
      to Debye-Huckel (DH) theory have to be considered. For non-bulk-like systems,
      such as isolated pairs or triples of macroions, we show that nonlinear effects
      can become relevant, which cannot be described by the charge renormalization
      concept [S. Alexander, J. Chem. Phys. 80, 5776 (1984)]. For an isolated pair of
      macroions, we find an almost perfect qualitative agreement between our simulation
      data and DH theory. However, on a quantitative level, neither DH theory nor the
      charge renormalization concept can be confirmed in detail. This seems mainly to
      be related to the fact that for small ion concentrations, microionic layers can
      strongly overlap, whereas, simultaneously, excluded volume effects are less
      important. In the case of isolated triples, where we compare between coaxial and
      triangular geometries, we find attractive corrections to pairwise additivity in
      the limit of small macroion separations and salt concentrations. These triplet
      interactions arise if all three microionic layers around the macroions exhibit a
      significant overlap. In contrast to the case of two isolated colloids, the charge
      distribution around a macroion in a triple is found to be anisotropic.

PMID- 17025420
TI  - Anisotropy of Brownian motion caused only by hydrodynamic interaction with a
      wall.
AB  - The diffusivity of spherical colloidal particles close to a planar hard wall is
      studied by dynamic light scattering with evanescent illumination. A novel setup
      allows us to independently vary the scattering vector components parallel Q
      parallel and normal Q perpendicular to the wall. An expression for the initial
      decay rate Gamma of the time autocorrelation functions is derived as a function
      of both Q parallel and Q perpendicular, as well as the penetration depth of the
      evanescent wave, where hydrodynamic interactions of particles with the wall are
      included. This makes it possible to study the viscous wall drag effect
      quantitatively for particles as small as 85 nm in radius.

PMID- 17025421
TI  - Shear viscosity of claylike colloids in computer simulations and experiments.
AB  - Dense suspensions of small strongly interacting particles are complex systems
      that are rarely understood on the microscopic level. We investigate properties of
      dense suspensions and sediments of small spherical Al2O3 particles in a shear
      cell by means of a combined molecular-dynamics and stochastic rotation dynamics
      simulation. We study structuring effects and the dependence of the suspension's
      viscosity on the shear rate and shear thinning for systems of varying salt
      concentration and pH value. To show the agreement of our results with
      experimental data, the relation between the bulk pH value and surface charge of
      spherical colloidal particles is modeled by Debye-Huckel theory in conjunction
      with a 2 pK charge regulation model.

PMID- 17025422
TI  - Self-assembly of the simple cubic lattice with an isotropic potential.
AB  - Conventional wisdom presumes that low-coordinated crystal ground states require
      directional interactions. Using our recently introduced optimization procedure to
      achieve self-assembly of targeted structures [M. C. Rechtsman, Phys. Rev. Lett.
      95, 228301 (2005); Phys. Rev. E 73, 011406 (2006)], we present an isotropic pair
      potential V(r) for a three-dimensional many-particle system whose classical
      ground state is the low-coordinated simple cubic lattice. This result is part of
      an ongoing pursuit by the authors to develop analytical and computational tools
      to solve statistical-mechanical inverse problems for the purpose of achieving
      targeted self-assembly. The purpose of these methods is to design interparticle
      interactions that cause self-assembly of technologically important target
      structures for applications in photonics, catalysis, separation, sensors, and
      electronics. We also show that standard approximate integral-equation theories of
      the liquid state that utilize pair correlation function information cannot be
      used in the reverse mode to predict the correct simple cubic potential. We report
      in passing optimized isotropic potentials that yield the body-centered-cubic and
      simple hexagonal lattices, which provide other examples of non-close-packed
      structures that can be assembled using isotropic pair interactions.

PMID- 17025423
TI  - Junction formation during desiccation cracking.
AB  - In order to provide a sound physical basis for the understanding of the formation
      of desiccation crack networks, an experimental study is presented addressing
      junction formation. Focusing on junctions, basic features of the network
      determining the final pattern, provides an elemental approach and imparts
      conceptual clarity to the rather complicated problem of the evolution of crack
      patterns. Using coffee-water mixtures a clear distinction between junction
      formation during nucleation and propagation is achieved. It is shown that for the
      same drying suspension, one can switch from the well-known symmetric triple
      junctions that are unique to the nucleation phase to propagation junctions that
      are purely dictated by the variations of the stress state. In the latter case,
      one can even manipulate the path of a propagating crack in a deterministic
      fashion by changing the stress state within the suspension. Clear microscopic
      evidence is provided for the formation of propagation junctions, and material
      inhomogeneity is observed to be reflected by a broad distribution of angles, in
      stark contrast to shrinkage cracks in homogeneous solid films.

PMID- 17025424
TI  - Measured long-ranged attractive interaction between charged polystyrene latex
      spheres at a water-air interface.
AB  - We report results of a systematic experimental study of interactions between
      charged polystyrene (PS) latex spheres at a water-air interface. Optical
      observations of stable bonded particle clusters and formation of circular
      chainlike structures at the interface demonstrate that the interaction potential
      is of dipole origin. Atomic force microscopy (AFM) is used to examine the
      distribution of charge groups on the colloidal surface. AFM phase images show
      patchy domains of size approximately 100 nm on the particle surface, indicating
      that the surface charge distribution of the PS spheres is not uniform, as is
      commonly believed. Such patchy charges can introduce fluctuating in-plane
      dipoles, leading to an attraction at short interparticle separations. A
      theoretical analysis is given to explain the mechanism for attractions between
      like-charged particles at the interface.

PMID- 17025425
TI  - Coarsening of three-dimensional grains in crystals, or bubbles in dry foams,
      tends towards a universal, statistically scale-invariant regime.
AB  - We perform extensive Potts model simulations of three-dimensional dry foam
      coarsening. Starting with 2.25 million bubbles, we have enough statistics to
      fulfill the three constraints required for the study of statistical scale
      invariance: first, enough time for the transient to end and reach the scaling
      state; then, enough time in the scaling state itself to characterize its
      properties; and finally, enough bubbles at the end to avoid spurious finite size
      effects. In the scaling state, we find that the average surface area of the
      bubbles increases linearly with time. The geometry (bubble shape and size) and
      topology (number of faces and edges), as well as their correlations, become
      constant in time. Their distributions agree with the data of the literature. We
      present an analytical model (universal, up to parameters extracted from the
      simulations) for a disordered foam minimizing its free energy, which agrees with
      the simulations. We discuss the limitations of the simulations and of the model.

PMID- 17025426
TI  - Evolution of the fractal-like aggregate system in colloids.
AB  - The evolution of a colloidal fractal-like aggregate system is studied
      theoretically with account for the reduction of the single-particle concentration
      in the space between these growing aggregates. Two different mechanisms of the
      initial aggregate formation are considered. They are heterogeneous aggregation,
      when the initial aggregates appear on foreign nuclei (the biggest particles,
      pollution, etc.), and homogeneous nucleation, when the initial clusters appear
      due to a random meeting and combination of single Brownian particles. The
      principles of colloid supersaturation decrease and the aggregate distribution in
      size are obtained in both cases as well as the internal structure of the
      clusters. Unlike the usual condensation-type phase transition, the system of
      discrete clusters is formed at the final stage of the aggregation process. The
      internal particle distribution in these clusters does not obey the universal
      scaling power law, which differs from the model case of separate cluster growth
      in an infinite colloidal medium with permanent concentration of free particles.

PMID- 17025427
TI  - Anomalous dynamic arrest in a mixture of large and small particles.
AB  - We present molecular dynamics simulations of the slow dynamics of a mixture of
      large and small soft spheres with a large size disparity. The dynamics are
      investigated in a broad range of temperature and mixture composition. As a
      consequence of the large size disparity, large and small particles exhibit very
      different relaxation times. As previously reported for simple models of short
      ranged attractive colloids and polymer blends, several anomalous dynamic features
      are observed: (i) sublinear behavior for mean-squared displacements, (ii) concave
      to-convex crossover for density-density correlators, by varying the temperature
      or wave vector, and (iii) logarithmic decay for specific wave vectors of density
      density correlators. These anomalous features are observed over time intervals
      extending up to four decades and strongly resemble predictions of the mode
      coupling theory (MCT) for state points close to higher-order MCT transitions,
      which originate from the competition between different mechanisms for dynamic
      arrest. For the large particles we suggest competition between soft-sphere
      repulsion and depletion effects induced by neighboring small particles. For the
      small particles we suggest competition between bulklike dynamics and confinement,
      respectively induced by neighboring small particles and by the slow matrix of
      large particles.

PMID- 17025428
TI  - Dynamical arrest and replica symmetry breaking in attractive colloids.
AB  - Within the replica symmetry breaking framework developed by Mezard and Parisi we
      investigate the occurrence of structural glass transitions in a model of fluid
      characterized by hard sphere repulsion together with short-range attraction. This
      model is appropriate for the description of a class of colloidal suspensions. The
      transition line in the density-temperature plane displays a reentrant behavior,
      in agreement with mode coupling theory and recent molecular dynamics simulations.
      Quantitative differences are found, together with the absence of the predicted
      glass-glass transition at high density. We also perform a systematic study of the
      pure hard-sphere fluid in order to ascertain the accuracy of the adopted method
      and the convergence of the numerical procedure.

PMID- 17025429
TI  - Computer simulation of diffusion-limited cluster-cluster aggregation with an
      Epstein drag force.
AB  - The motion of particles, dispersed in a medium, between collisions with each
      other can, in limiting situations, be either ballistic (straight line) or
      diffusive (random walker). The diffusive regime can be divided into two distinct
      subregimes. The "continuum regime" exhibits Stokes-Einstein-type diffusion (no
      slip surface boundary condition) with a frictional coefficient proportional to
      the particle size (linear dimension). The "Epstein regime," as we shall refer to
      it, is characterized by a frictional coefficient proportional to the particle
      cross-sectional area, hence an Epstein-type diffusion (slip surface). The purpose
      of the current study is to illuminate the dynamics of dilute-limit aggregation in
      the Epstein regime. We present results from low volume fraction Monte Carlo
      simulations of cluster-cluster aggregation in the Epstein regime with the
      particle motion based on each particle's cross-sectional area. Our findings
      indicate that aggregates grown under Epstein conditions have a fractal dimension
      of approximately 1.8, similar to that of diffusion-limited cluster-cluster
      aggregates (DLCA) in the continuum regime. The kinetic exponent z in the Epstein
      regime is found to be z approximately 0.8, lower than its value for both the
      continuum regime DLCA (z = 1) and for the ballistic cluster aggregation regime (z
      approximately 2). Cluster size distribution data for Epstein systems are found to
      scale at large cluster sizes with exponents consistent with the kinetic data. A
      scaling argument for predicting the kinetic exponent and kernel homogeneity based
      on the mass or size dependence of the particle velocity and collision cross
      section is presented and is seen to give accurate results for dilute and
      intermediate values of particle volume fractions not only for the current study,
      but also for work done by other researchers with various choices for the
      aggregation kernel.

PMID- 17025430
TI  - Rayleigh instability of charged aggregates: Role of the dimensionality, ionic
      strength, and dielectric contrast.
AB  - We extended a previous analysis of the classical Rayleigh instability of
      spherical charged droplets in the presence of neutralizing monovalent counterions
      [M. Deserno, Eur. Phys. J. E 6, 163 (2001)], by generalizing the problem for
      suspensions of aggregates with D-dimensional symmetry, corresponding for D = 2 to
      infinite (rodlike) cylindrical charged bundles and for D = 3 to spherical charged
      droplets. In addition, we include the effects of added monovalent salt and of
      dielectric contrast between the charged aggregate and the surrounding solvent.
      The electrostatic energy taking the microion screening into account is estimated
      using uniform profiles within the framework of the cell model. We verify the
      robustness of these results by also considering Debye-Huckel-type microion
      profiles that are obtained by the minimization of a linearized Poisson-Boltzmann
      free-energy functional. In the case when the microions can enter inside the
      charged aggregates, we confirm the occurrence of a discontinuous phase change
      between aggregates of finite size and an infinite aggregate, which takes place at
      a collapse temperature that depends on their volume fraction phi and on the salt
      content. Decrease of phi shifts the phase-change temperature toward higher
      values, while salt addition has an opposite effect. We obtain analytical
      expressions for the phase-separation line in the asymptotic limit of infinite
      dilution (phi-->0), showing that the collapse temperature depends logarithmically
      on phi . As an application for D = 3 we discuss the stability of the pearl
      necklace structures of flexible polyelectrolytes in poor solvents. The case D = 2
      is applied to the problem of finite bundle sizes of stiff polyelectrolytes that
      attract each other-via, e.g., multivalent counterions-leading to an effective
      surface tension.

PMID- 17025431
TI  - Glass transition in 1,4-polybutadiene: Mode-coupling theory analysis of molecular
      dynamics simulations using a chemically realistic model.
AB  - We present molecular dynamics simulations of the glass transition in a chemically
      realistic model of 1,4-polybutadiene (PBD). Around 40 K above the calorimetric
      glass transition of this polymer the simulations reveal a well-developed two
      stage relaxation of all correlation functions. We have analyzed the time-scale
      separation between vibrational degrees of freedom (subpicosecond dynamics) and
      the alpha relaxation behavior (nanosecond to microsecond dynamics) using the
      predictions of mode-coupling theory (MCT). Our value for the mode-coupling
      critical temperature Tc agrees perfectly with prior experimental estimates for
      PBD. The predictions of MCT for the scaling behavior of the so-called beta
      relaxation, the plateau regime separating vibrational dynamics and the alpha
      relaxation, are well fulfilled. Furthermore, we are able to derive a consistent
      set of MCT exponents, completely characterizing the scaling behavior of
      relaxation processes in the vicinity of Tc. For the temperature dependence of the
      alpha relaxation we find deviations from MCT predictions which we trace to the
      influence of torsional barriers on the atomic motions.

PMID- 17025432
TI  - Solidity of viscous liquids. IV. Density fluctuations.
AB  - This paper is the fourth in a series exploring the physical consequences of the
      solidity of highly viscous liquids. It is argued that the two basic
      characteristics of a flow event (a jump between two energy minima in
      configuration space) are the local density change and the sum of all particle
      displacements. Based on this it is proposed that density fluctuations are
      described by a time-dependent Ginzburg-Landau equation with rates in k space of
      the form Gamma0 + Dk2 with D >> Gamma0a2 where a is the average intermolecular
      distance. The inequality expresses a long-wavelength dominance of the dynamics
      which implies that the Hamiltonian (free energy) may be taken to be ultralocal.
      As an illustration of the theory the case with the simplest nontrivial
      Hamiltonian is solved to second order in the Gaussian approximation, where it
      predicts an asymmetric frequency dependence of the isothermal bulk modulus with
      Debye behavior at low frequencies and an omega(-1/2) decay of the loss at high
      frequencies. Finally, a general formalism for the description of viscous liquid
      dynamics, which supplements the density dynamics by including stress fields, a
      potential energy field, and molecular orientational fields, is proposed.

PMID- 17025433
TI  - Phase behavior of a hard sphere Maier-Saupe nematogenic system in three
      dimensions.
AB  - We present a detailed computer simulation and integral equation study of the
      phase behavior of a nematogenic system composed of hard spheres with embedded
      three-dimensional Maier-Saupe spins. For this well-known system, we map the gas
      liquid equilibrium, which is coupled to a first-order isotropic-nematic
      transition. The anisotropic integral equation theory is found to yield excellent
      agreement with the simulation data within the fluid regime. Additionally, we
      determine the fluid-solid equilibrium transition by means of computer simulation.

PMID- 17025434
TI  - Constitutive law describing the phenomenology of subyield mechanically stimulated
      glasses.
AB  - The principal features of the volumetric as well as the viscoelastic response of
      mechanically stimulated glasses can be summarized as follows: (i) the time-aging
      time shift factors contract upon increasing the probe stress (i.e., the stress
      apparently modifies the volume recovery kinetics), (ii) the volume recovery
      baseline remains unaltered (i.e., the underlying structure of the stimulated
      glass remains unchanged). Here we present a series of numerically simulated
      results concerning the responses of glassy polycarbonate that simultaneously
      fulfill these apparent contradictions. The problem was tackled coupling a
      modified Kalroush, Aklonis, Hotchinson, Ramos equation with the constitutive law
      for linear viscoelasticity within the domain of the reduced time. It was argued
      that the relaxation times under isobaric conditions depend on the temperature,
      the dimensionless volume, and the isotropic components of the stress tensor.
      Simulations are obtained with a minimum of experimental ( PVT and linear
      viscoelastic) data inputs. Different loading protocols consisting of complex
      combinations and/or sequences of large and small mechanical stimuli were tested.
      Volumetric as well as viscoelastic behavior are systematically reported. A
      tentative explanation of the origin of the time-aging time contraction was
      finally proposed while some additional features concerning the volumetric
      response emerged.

PMID- 17025435
TI  - Anisotropic instability of a dielectric liquid in a strong uniform electric
      field: Decay into a two-phase system of vapor filaments in a liquid.
AB  - The linear stability analysis of dielectric liquid placed in uniform electric
      field with respect to perturbations of density of an initially uniform state was
      carried out. The electric field increases the instability increment for the
      stratification along the field and decreases it for the transversal
      stratification. Thus, anisotropic separation into liquid and vapor phases is
      possible in high electric fields for a liquid that is initially in unstable
      state, as well as in metastable or stable states. Computer simulations of
      electrohydrodynamics confirm the theoretical calculations. It is important that
      new regions of low density phase appear as narrow cylindrical channels oriented
      along the field. This mechanism of generation of gaseous phase in locally high
      electric field can play a key role in processes of inception and ultrafast
      propagation of streamers during breakdown of liquid dielectrics in nanosecond
      range.

PMID- 17025436
TI  - Relaxation in the glass former acetylsalicylic acid studied by deuteron magnetic
      resonance and dielectric spectroscopy.
AB  - Supercooled liquid and glassy acetylsalicylic acid was studied using dielectric
      spectroscopy and deuteron relaxometry in a wide temperature range. The
      supercooled liquid is characterized by major deviations from thermally activated
      behavior. In the glass the secondary relaxation exhibits the typical features of
      a Johari-Goldstein process. Via measurements of spin-lattice relaxation times the
      selectively deuterated methyl group was used as a sensitive probe of its local
      environments. There is a large difference in the mean activation energy in the
      glass with respect to that in crystalline acetylsalicylic acid. This can be
      understood by taking into account the broad energy barrier distribution in the
      glass.

PMID- 17025437
TI  - Four-point susceptibility of a glass-forming binary mixture: Brownian dynamics.
AB  - We study the four-point dynamic susceptibility chi4(t) obtained from Brownian
      dynamics computer simulations of the Kob-Andersen Lennard-Jones mixture. We
      compare the results of the simulations with qualitative predictions of the mode
      coupling theory. In addition, we test an estimate of the four-point
      susceptibility recently proposed by Berthier [Science 310, 1797 (2005)].

PMID- 17025438
TI  - Field-theoretic description of ionic crystallization in the restricted primitive
      model.
AB  - Effects of charge-density fluctuations on a phase behavior of the restricted
      primitive model are studied within a field-theoretic formalism. We focus on a
      lambda line of continuous transitions between charge-ordered and charge
      disordered phases that is observed in several mean-field theories, but is absent
      in simulation results. In our study the RPM is reduced to a phi(6) theory, and a
      fluctuation contribution to a grand thermodynamic potential is obtained by
      generalizing the Brazovskii approach. We find that in a presence of fluctuations
      the lambda -line disappears. Instead, a fluctuation-induced first-order
      transition to a charge-ordered phase appears in the same region of a phase
      diagram, where the liquid-ionic-crystal transition is obtained in simulations.
      Our results indicate that the charge-ordered phase should be identified with an
      ionic crystal.

PMID- 17025439
TI  - Mesoscopic modeling of a two-phase flow in the presence of boundaries: The
      contact angle.
AB  - We present a mesoscopic model, based on the Boltzmann equation, for the
      interaction between a solid wall and a nonideal fluid. We present an analytic
      derivation of the contact angle in terms of the surface tension between the
      liquid-gas, the liquid-solid, and the gas-solid phases. We study the dependency
      of the contact angle on the two free parameters of the model, which determine the
      interaction between the fluid and the boundaries, i.e. the equivalent of the wall
      density and of the wall-fluid potential in molecular dynamics studies. We compare
      the analytical results obtained in the hydrodynamical limit for the density
      profile and for the surface tension expression with the numerical simulations. We
      compare also our two-phase approach with some exact results obtained by E. Lauga
      and H. Stone [J. Fluid. Mech. 489, 55 (2003)] and J. Philip [Z. Angew. Math.
      Phys. 23, 960 (1972)] for a pure hydrodynamical incompressible fluid based on
      Navier-Stokes equations with boundary conditions made up of alternating slip and
      no-slip strips. Finally, we show how to overcome some theoretical limitations
      connected with the discretized Boltzmann scheme proposed by X. Shan and H. Chen
      [Phys. Rev. E 49, 2941 (1994)] and we discuss the equivalence between the surface
      tension defined in terms of the mechanical equilibrium and in terms of the
      Maxwell construction.

PMID- 17025440
TI  - Modeling the elastic deformation of polymer crusts formed by sessile droplet
      evaporation.
AB  - Evaporating droplets of polymer or colloid solution may produce a glassy crust at
      the liquid-vapor interface, which subsequently deforms as an elastic shell. For
      sessile droplets, the known radial outward flow of solvent is expected to
      generate crusts that are thicker near the pinned contact line than the apex. Here
      we investigate, by nonlinear quasistatic simulation and scaling analysis, the
      deformation mode and stability properties of elastic caps with a nonuniform
      thickness profile. By suitably scaling the mean thickness and the contact angle
      between crust and substrate, we find that data collapse onto a master curve for
      both buckling pressure and deformation mode, thus allowing us to predict when the
      deformed shape is a dimple, Mexican hat, and so on. This master curve is
      parameterized by a dimensionless measure of the nonuniformity of the shell. We
      also speculate on how overlapping time scales for gelation and deformation may
      alter our findings.

PMID- 17025441
TI  - Surface freezing in binary alkane-alcohol mixtures.
AB  - Surface freezing was detected and studied in mixtures of alcohol and alkane
      molecules, using surface tensiometry and surface-specific x-ray scattering
      methods. Considering that surface freezing in pure alkanes forms an ordered
      monolayer and in alcohols it forms an ordered bilayer, the length mismatch
      repulsion was minimized by varying the carbon number of the alkane component
      around 2n, where n is the carbon number of the alcohol molecule. A solutionlike
      behavior was found for all mixtures, where the ideal liquid mixture phase
      separates upon freezing both in the bulk and the surface. The solid exhibits a
      herringbone crystalline phase below an alkane mole fraction phi(t) approximately
      0.8 and a rotator phase above it. The surface frozen film below phi(t) is an
      alkane monolayer exhibiting a next-nearest neighbor molecular tilt of a
      composition-dependent magnitude. Above phi(t), no diffraction peaks were
      observed. This could be explained by the intrinsically shorter-range order of the
      rotator phase and a possible proliferation of defects.

PMID- 17025442
TI  - Ginzburg-Landau theory of the liquid-solid interface and nucleation for hard
      spheres.
AB  - The Ginzburg-Landau free energy functional for hard spheres is constructed using
      the fundamental measure theory approach to density functional theory as a
      starting point. The functional is used to study the liquid-fcc solid planer
      interface and the properties of small solid clusters nucleating within a liquid.
      The surface tension for planer interfaces agrees well with simulation and it is
      found that the properties of the solid clusters are consistent with classical
      nucleation theory.

PMID- 17025443
TI  - Inverse method for the determination of a mathematical expression for the
      anisotropy of the solid-liquid interfacial energy in Al-Zn-Si alloys.
AB  - An expression for the anisotropy of the solid-liquid interfacial energy has been
      determined experimentally by an inverse method for the Al-43.4 wt%Zn-1.6 wt%Si
      system. Assuming that dendrite growth directions correspond to the minima of the
      surface stiffness, the anisotropy of the solid-liquid interfacial energy could be
      described by minimizing the errors between the calculated minima of a parametric
      interface stiffness function and experimentally measured growth directions of
      dendrites in thin coatings. In order to adequately describe the interfacial
      energy, it is found that a cubic harmonic expansion up to the third order is
      necessary to obtain the minima of interface stiffness along directions that
      depart from <100> or <110>. Best agreement with observed growth directions is
      obtained for first, second, and third harmonic coefficients (epsilon1, epsilon2,
      and epsilon3, respectively) satisfying the following relationships:
      epsilon2/epsilon1 = -0.188; epsilon3/epsilon1 = -0.00776. The corresponding
      interface stiffness function shows 24 minima lying along directions between <100>
      and <110>. The minima are located at 28.5 degrees from <100> and only 5.1 degrees
      from <320>, which was the growth direction suggested by Semoroz for this alloy
      [A. Semoroz, Y. Durandet, and M. Rappaz, Acta Mater. 49, 529 (2001).]. It was
      also found that the strength of the effective in-plane anisotropy is directly
      reflected by the morphology of the dendritic microstructure.

PMID- 17025444
TI  - Nucleation and growth of droplets at a liquid-gas interface.
AB  - The nucleation of liquid droplets at a liquid-gas interface from a saturated
      vapor in the gas phase, as well as the droplet growth after the nucleation are
      studied. These two processes determine the formation of a regular hexagonal array
      of drops on the surface of an evaporating film of polymer solution that is used
      for the fabrication of polymer membranes with a regular microporous structure.
      The free-energy barrier for the nucleation of a droplet at a liquid-gas interface
      is found as a function of the droplet radius and the contact angles, and the
      critical nucleation radius is computed. It is shown that the heterogeneous
      nucleation is thermodynamically more preferable than the homogeneous one. The
      role of the line tension between the phases is also estimated. Further growth of
      a droplet nucleated at the liquid-gas interface is studied. Two growth mechanisms
      are considered: by the vapor diffusion flux from the gas phase and by the surface
      diffusion of the vapor molecules adsorbed at the liquid-gas interface outside the
      droplet. Two cases, corresponding to unsaturated and saturated condensation, are
      considered. The droplet growth is described by a free-boundary problem which is
      solved analytically and numerically. The droplet growth exponents at different
      stages of growth are found.

PMID- 17025445
TI  - Upper critical dimension for irreversible cluster nucleation and growth in the
      point-island regime.
AB  - We compare the results of kinetic Monte Carlo (KMC) simulations of a point-island
      model of irreversible nucleation and growth in four dimensions (4D) with the
      corresponding mean-field (MF) rate-equation predictions for the monomer density,
      island density, island-size distribution (ISD), capture-number distribution
      (CND), and capture-zone distribution (CZD), in order to determine the critical
      dimension d(c) for mean-field behavior. The asymptotic behavior is studied as a
      function of the fraction of occupied sites (coverage) and the ratio DF of the
      monomer hopping rate D to the (per site) monomer creation rate F. Excellent
      agreement is found between our KMC simulation results and the MF rate equation
      results for the average island and monomer densities. For large D/F, the scaled
      CND and CZD do not depend on island size, in good agreement with the MF
      prediction, while the scaled ISD also agrees well with the MF prediction except
      for a slight difference at the peak values. Coupled with previous results
      obtained in d = 3 , these results indicate that for growth in the point-island
      regime, the upper critical dimension for irreversible cluster nucleation and
      growth is equal to 4.

PMID- 17025446
TI  - Structure of a liquid crystalline fluid around a macroparticle: Density
      functional theory.
AB  - The structure of a molecular liquid, in both the nematic liquid crystalline and
      isotropic phases, around a cylindrical macroparticle, is studied using density
      functional theory. In the nematic phase the structure of the fluid is highly
      anisotropic with respect to the director, in agreement with results from
      simulation and phenomenological theories. On going into the isotropic phase the
      structure becomes rotationally invariant around the macroparticle with an
      oriented layer at the surface.

PMID- 17025447
TI  - Polar order and tilt in achiral smectic phases.
AB  - Material with the phase sequence SmA-SmAP-SmCP is studied as an example of a
      system in which the spontaneous electric polarization and the molecular tilt
      develop independently at the SmA-SmAP and the SmAP-SmCP phase transition,
      respectively. The temperature dependence of the spontaneous electric polarization
      clearly shows a strong coupling between the polarization and tilt. The system
      exhibits also very strong precritical polarization and tilt fluctuations.
      Experimental observations are explained within the theoretical model.

PMID- 17025448
TI  - Mesomorphism in columnar phases studied by solid-state nuclear magnetic
      resonance.
AB  - In this paper, we present 13C and 1H NMR investigations of 2, 3, 6, 7, 10, 11
      hexahexyl-thiotriphenylene (HHTT). The measurements were carried out under both
      static and magic-angle spinning conditions. The phase diagram of HHTT is K<-->H<-
      >D(hd)<-->I , where H is a helical phase and D(hd) is a columnar liquid crystal.
      The motivation was to characterize the molecular order and dynamics and to
      investigate differences at the molecular level between the two mesophases: H and
      D(hd). It is shown that D(hd) is a conventional columnar liquid crystal, where
      the molecular core undergoes fast rotation about the symmetry axis. The
      orientational order in this mesophase is lower and the temperature dependence of
      the order parameter is steeper than in other triphenylene-based compounds. On the
      other hand, in the helical phase the core, similarly to the solid phase, is
      essentially rigid. The difference between the solid and helical phases is mainly
      manifested in an increased mobility of the aliphatic chains observed in the
      latter phase. In addition, the sample exhibits thermal history effects, which are
      observed in the different behavior upon cooling and heating.

PMID- 17025449
TI  - Interpretation of the odd-even behavior for the emergence of ferroelectricity and
      antiferroelectricity in bent-core mesogens.
AB  - Simple theoretical interpretation has been made on the previously reported odd
      even behavior of the emergence of ferroelectricity and antiferroelectricity in
      homologous series of bent-core mesogens with the same chiral end chains (S,S) ;
      compounds with even and odd carbon numbers (including oxygen) exhibit
      ferroelectric and antiferroelectric B2 phases, respectively. The odd-even
      behavior was confirmed in newly synthesized racemic compounds with chiral end
      chains of R and S forms (R,S) together with (R,R) and (S,S) forms. According to
      our theoretical interpretation, ferroelectricity should be more stable in (R,S)
      compounds than in (S,S) compounds. Actually, the transition temperature from the
      isotropic phase to the Sm-CP phase was higher and the temperature range of the B2
      phase was broader in the (R,S) compound than in the (S,S) compound.

PMID- 17025450
TI  - Emergence of hexatic and threefold hidden order in two-dimensional smectic liquid
      crystals: A Monte Carlo study.
AB  - Using a high resolution Monte Carlo simulation technique based on a
      multihistogram method and cluster algorithm, we have investigated the critical
      properties of a coupled XY model, consisting of a sixfold symmetric hexatic and a
      hidden order parameter of threefold symmetry in two dimensions. The simulation
      results demonstrate a series of continuous transitions in which both kinds of
      orderings are established simultaneously. It is found that the specific-heat
      anomaly exponents for some regions in coupling constants space are in excellent
      agreement with the experimentally measured exponents extracted from heat-capacity
      data near the smectic- A -hexatic- B transition of two-layer free standing films.

PMID- 17025451
TI  - Elliptical soft colloids in smectic-C films.
AB  - We investigate theoretically the elliptical shapes of soft colloids in freely
      standing smectic- C films, that have been reported recently. The colloids favor
      parallel alignment of the liquid crystal molecules at their surfaces and, for
      sufficiently strong anchoring, will generate a pair of defects at the poles of
      the colloidal particles. The elastic free energy of the liquid crystal matrix
      will, in turn, affect the shape of the colloids. In this study we will focus on
      elliptical soft colloids and determine how their equilibrium shapes depend on the
      elastic constants of the liquid crystal, the anchoring strength, the surface
      tension, and the size of the colloids. A shape diagram is obtained analytically,
      by minimizing the Frank elastic free energy, in the limit of small
      eccentricities. The analytical results are verified, and generalized to arbitrary
      eccentricities, by numerical minimization of an appropriate Landau free energy.
      The latter is required for an adequate description of the topological defects
      when the liquid crystal correlation length is comparable to the size of the
      colloidal particles.

PMID- 17025452
TI  - Temperature dependence of optical anisotropy of holographic polymer-dispersed
      liquid crystal transmission gratings.
AB  - We measured the angular dependence of the 0th, +/-1 st, and +/-2 nd optical
      diffraction orders from a 50 microm thick transmission grating recorded in a UV
      curable holographic polymer-dispersed liquid crystal (HPDLC) made from
      commercially available constituents. The analysis was performed for two
      orthogonal polarizations of the probe beams. The emphasis was laid on the
      temperature dependence of the grating anisotropy. Above the nematic-isotropic
      phase transition, the grating is optically isotropic. At lower temperatures the
      grating strength for the optical polarization perpendicular to the grating vector
      decreases with decreasing temperature, while for orthogonal polarization it
      increases with decreasing temperature. As a consequence, a regime of diffraction
      with strongly overmodulated gratings is observed. Our investigations indicate
      that the anisotropy of the refractive-index modulation scales with the optical
      anisotropy of the liquid crystal medium forming the phase-separated domains. We
      further demonstrate that light scattering effects, which are profound only in the
      nematic phase, must not be neglected and can be taken into account via a
      Lorentzian line-shape broadening of the probing wave vector directions in the
      framework of the diffraction theory for anisotropic optical phase gratings.

PMID- 17025453
TI  - Mechanical strains and electric fields applied to topologically imprinted
      elastomers.
AB  - We analyze and predict the behavior of a chirally imprinted elastomer under a
      mechanical strain and an electric field, applied along the helical axis. As the
      strain and/or field increases, the system is deformed from a conical or
      transverse imprinted state towards an ultimately nematic one. At a critical
      strain and/or field there is a first-order transition to a low imprinting
      efficiency state. This transition is accompanied by a discontinuous global
      rotation of the director toward the axis of the imprinted helix, measured by the
      cone angle, theta . We show that the threshold electric field required for
      switching this transition can be conveniently low, provided an appropriate
      prestrain is imposed. We suggest that these properties may give rise to a "chiral
      pump."

PMID- 17025454
TI  - Measurement of the viscosity coefficient eta3 in free-standing smectic films.
AB  - Thinner parts (the so-called holes) and thicker parts (islands) move in free
      standing smectic films due to gravity if the film is inclined. The velocity of
      the movement depends on the viscosity coefficient eta3 of the film. Therefore,
      this measurement is a direct method to determine eta3 in smectic phases. This
      paper contains the corresponding hydrodynamic calculations for the flow patterns
      in and around a circular hole in a circular two-dimensional film under various
      conditions. The viscous force on the hole is calculated. Experiments are
      performed with the liquid crystal n-octyl-cyano-biphenyl (8CB) in the smectic
      phase. The influence of the disclination which surrounds the hole and the
      influence of the gas which surrounds the film on the movement is studied. It is
      shown that the influence of these effects on the determination of eta3 can be
      neglected if the film is thick and the difference in the thicknesses between film
      and hole is small. The temperature dependence of eta3 is determined for 8CB.

PMID- 17025455
TI  - Theory of the isotropic-nematic transition in dispersions of compressible rods.
AB  - We theoretically study the nematic ordering transition of rods that are able to
      elastically adjust their mutually excluded volumes. The model rods, which consist
      of a hard core surrounded by a deformable shell, mimic the structure of polymer
      coated, rodlike fd virus particles that have recently been the object of
      experimental study [K. Purdy, Phys. Rev. Lett. 94, 057801 (2005)]. We find that
      fluids of such soft rods exhibit an isotropic-nematic phase transition at a
      density higher than that of the corresponding hard-rod system of identical
      diameter, and that at coexistence the order parameter of the nematic phase
      depends nonmonotonically on the elastic properties of the polymer coating. For
      binary mixtures of hard and soft rods, the topology of the phase diagram turns
      out to depend sensitively on the elasticity of a shell. The lower nematic-nematic
      critical point, discovered in mixtures of bare and polymer-coated fd virus
      particles, is not reproduced by the theory.

PMID- 17025456
TI  - Nematic textures in spherical shells.
AB  - The equilibrium texture of nematic shells is studied as a function of their
      thickness. For ultrathin shells the ground state has four short 1/2 disclination
      lines but, as the thickness of the film increases, a three-dimensional escaped
      configuration composed of two pairs of half-hedgehogs becomes energetically
      favorable. We derive an exact solution for the nematic ground state in the one
      Frank constant approximation and study the stability of the corresponding texture
      against thermal fluctuations.

PMID- 17025457
TI  - Quadrupolar projection of excluded-volume interactions in biaxial nematic liquid
      crystals.
AB  - We compute the quadrupolar approximation to the excluded-volume interaction
      between hard spherocuboids, which applies to both platelets and spheroplatelets
      as special cases. We show that this approximation can be written as the
      superposition of two London interactions: one attractive and the other repulsive.
      This conclusion also proves why the phase diagram for the excluded-volume
      interaction of spherocuboids is expected to feature a direct isotropic-to-biaxial
      transition at a single Landau point.

PMID- 17025458
TI  - Macroscopic dynamics of polar nematic liquid crystals.
AB  - We present the macroscopic equations for polar nematic liquid crystals. We
      consider the case where one has both, the usual nematic director, n[over ] ,
      characterizing quadrupolar order as well as the macroscopic polarization, P ,
      representing polar order, but where their directions coincide and are rigidly
      coupled. In this case one has to choose P as the independent macroscopic
      variable. Such equations are expected to be relevant in connection with nematic
      phases with unusual properties found recently in compounds composed of banana
      shaped molecules. Among the effects predicted, which are absent in conventional
      nematic liquid crystals showing only quadrupolar order, are pyro-electricity and
      its analogs for density and for concentration in mixtures as well as a flow
      alignment behavior, which is more complex than in usual low molecular weight
      nematics. We also discuss the formation of defect structures expected in such
      systems.

PMID- 17025459
TI  - Transitions in the orientational order of liquid crystals induced by periodic
      patterned substrates.
AB  - The orientational order of liquid crystals (LCs) induced by periodic patterned
      substrates has been investigated with cells coated by azopolymer films that could
      be photoaligned in a controlled way. Two regimes were observed depending on the
      period of the patterns: (i) above 3.0 microm the LC follows the direction imposed
      by the patterned substrate since the energy stored in the surface potential
      minimizes the elastic energy of the LC medium. (ii) For periods smaller than 1.0
      microm a homogeneous in-plane state was induced and the LC did not follow the
      orientation imposed by the surface. This in-plane transition could be explained
      qualitatively by a theoretical model based on the competition between the Frank
      Oseen elastic energy and the phenomenological surface potential. The results also
      suggest an out-of-plane transition for the LC director as the period was reduced.
      These results agree with data in the literature for patterned substrates with
      completely distinct architectures. This indicates that for a particular LC sample
      the overall behavior depends basically on the texture period instead of the
      texture architecture. The textures were characterized with a scanning near-field
      optical microscope (SNOM), which allowed simultaneous morphological and optical
      images in the submicrometer range.

PMID- 17025460
TI  - Low-energy excitations and the fast process of polystyrene thin supported films
      studied by inelastic and quasielastic neutron scattering.
AB  - We studied the low-energy excitations in the meV region as well as the picosecond
      fast process in polystyrene thin supported films using inelastic and quasielastic
      neutron scattering in a temperature range from 11 to 430 K , covering the bulk
      glass transition temperature Tg. It was found that the mean square displacement
      u2 decreased with the film thickness below and above the glass transition
      temperature Tg, suggesting that the hardening occurs with decreasing the film
      thickness. Corresponding to the decrease in u2, it was also found that the
      density of phonon states G(omega) decreased with film thickness. This decrease
      occurs mainly in the Debye mode while the contribution of the boson peak mode
      also decreases with the film thickness without changing the boson peak energy. As
      for the fast process, which appeared above at about 150 K as a quasielastic
      scattering, the fraction A(fast)(Q) decreased with the film thickness in a
      similar manner with the boson peak without changing the relaxation rate,
      suggesting a common origin for the boson peak and the fast process. These
      observations showing the hardening were well explained by assuming a hard dense
      layer at the interface, where the numbers of the boson peak mode as well as the
      fast process are less than the bulk state.

PMID- 17025461
TI  - Dissipative particle dynamics study on the morphology changes of diblock
      copolymer lamellar microdomains due to steady shear.
AB  - The morphology changes of linear diblock copolymer lamellar microdomains under
      uniform simple shear are studied via the dissipative particle dynamics technique.
      The parallel and perpendicular reorientations of the lamellae are observed in the
      simulations, and two different reorientation mechanisms, under small and large
      shear rates respectively, are proposed. The parallel-to-perpendicular transition
      is also observed and the kinetics is discussed. Sinusoidal and chevron
      instabilities due to the shear are found. After relaxation the peculiar
      "bidirectionally undulating" instability is obtained.

PMID- 17025462
TI  - Phase behavior of polyelectrolyte-surfactant complexes at planar surfaces.
AB  - We investigate theoretically the phase diagram of an insoluble charged surfactant
      monolayer in contact with a semidilute polyelectrolyte solution (of opposite
      charge). The polyelectrolytes are assumed to have long-range and attractive
      (electrostatic) interaction with the surfactant molecules. In addition, we
      introduce a short-range (chemical) interaction which is either attractive or
      repulsive. The surfactant monolayer can have a lateral phase separation between
      dilute and condensed phases. Three different regimes of the coupled system are
      investigated depending on system parameters. A regime where the polyelectrolyte
      is depleted due to short range repulsion from the surface, and two adsorption
      regimes, one being dominated by electrostatics, whereas the other by short range
      chemical attraction (similar to neutral polymers). When the polyelectrolyte is
      more attracted (or at least less repelled) by the surfactant molecules as
      compared with the bare water-air interface, it will shift upwards the surfactant
      critical temperature. For repulsive short-range interactions the effect is
      opposite. Finally, the addition of salt to the solution is found to increase the
      critical temperature for attractive surfaces, but does not show any significant
      effect for repulsive surfaces.

PMID- 17025463
TI  - Large-time dynamics and aging of a polymer chain in a random potential.
AB  - We study the out-of-equilibrium large-time dynamics of a Gaussian polymer chain
      in a quenched random potential. The dynamics studied is a simple Langevin
      dynamics commonly referred to as the Rouse model. The equations for the two-time
      correlation and response functions are derived within the Gaussian variational
      approximation. In order to implement this approximation faithfully, we employ the
      supersymmetric representation of the Martin-Siggia-Rose dynamical action. For a
      short-ranged correlated random potential the equations are solved analytically in
      the limit of large times using certain assumptions concerning the asymptotic
      behavior. Two possible dynamical behaviors are identified depending upon the time
      separation: a stationary regime and an aging regime. In the stationary regime
      time translation invariance holds and so does the fluctuation dissipation
      theorem. The aging regime which occurs for large time separations of the two-time
      correlation functions is characterized by a history dependence and the breakdown
      of certain equilibrium relations. The large-time limit of the equations yields
      equations among the order parameters that are similar to the equations obtained
      in statics using replicas. In particular the aging solution corresponds to the
      broken replica solution. But there is a difference in one equation that leads to
      important consequences for the solution. The stationary regime corresponds to the
      motion of the polymer inside a local minimum of the random potential, whereas in
      the aging regime the polymer hops between different minima. As a by-product we
      also solve exactly the dynamics of a chain in a random potential with quadratic
      correlations.

PMID- 17025464
TI  - Flexible ring polymers in an obstacle environment: Molecular theory of linear
      viscoelasticity.
AB  - We formulate a coarse-grained mean-field approach to study the dynamics of the
      flexible ring polymer in any given obstacle (gel or melt) environment. The
      similarity of the static structure of the ring polymer with that of the ideal
      randomly branched polymer is exploited in formulating the dynamical model using
      aspects of the pom-pom model for branched polymers. The topological constraints
      are handled via the tube model framework. Based on our formulation we obtain
      expressions for diffusion coefficient D, relaxation times tau, and dynamic
      structure factor g(k,t). Further, based on the framework we develop a molecular
      theory of linear viscoelasticity for ring polymers in a given obstacle
      environment and derive the expression for the relaxation modulus G(t). The
      predictions of the theoretical model are in agreement with previously proposed
      scaling arguments and in qualitative agreement with the available experimental
      results for the melt of rings.

PMID- 17025465
TI  - Adsorption and desorption of reversible supramolecular polymers.
AB  - We report numerical mean-field results on the quasichemical level of
      approximation that describe adsorption of reversible supramolecular polymers at a
      flat interface. Emphasis is laid on the regime of strong adsorption from a dilute
      solution. There are two differences with respect to macromolecular polymer
      adsorption: (i) adsorption sets in at relatively high monomer concentrations of
      the surrounding solution, and (ii) the surface is filled within a much narrower
      concentration range. Contrary to macromolecular polymers, supramolecular polymers
      can therefore be desorbed by dilution of the equilibrium solution by solvent
      within an experimentally accessible concentration window. Based on simple
      thermodynamic arguments, we provide a quantitative explanation why supramolecular
      polymers adsorb at relatively high concentrations. Moreover, we discuss the (by
      comparison) narrow concentration window wherein filling of the surface occurs.
      This is attributed to the cooperative nature of supramolecular polymer
      adsorption. The degree of cooperativity is quantified by means of the Hill
      parameter n.

PMID- 17025466
TI  - Geometrical approach to tumor growth.
AB  - Tumor growth has a number of features in common with a physical process known as
      molecular beam epitaxy. Both growth processes are characterized by the constraint
      of growth development to the body border, and surface diffusion of cells and
      particles at the growing edge. However, tumor growth implies an approximate
      spherical symmetry that makes necessary a geometrical treatment of the growth
      equations. The basic model was introduced in a former paper [C. Escudero, Phys.
      Rev. E 73, 020902(R) (2006)], and in the present work we extend our analysis and
      try to shed light on the possible geometrical principles that drive tumor growth.
      We present two-dimensional models that reproduce the experimental observations,
      and analyze the unexplored three-dimensional case, for which interesting
      conclusions on tumor growth are derived.

PMID- 17025467
TI  - Continuous probabilistic approach to species dynamics in Hubbell's zero-sum local
      community.
AB  - In this paper a continuous probabilistic approach formulated using Kolmogorov
      Fokker-Planck forward and backward models is applied to Hubbell's zero-sum
      neutral theory for species dynamics in local community. Using this technique the
      probability density of species abundance, distribution of the first passage time
      to extinction or fixation and probability of extinction are defined. The
      resulting values for the distribution of the first passage time to extinction are
      verified by the simulation study of Hubbell's zero-sum neutral model for the
      local community. Based on the sensitivity analysis for the continuous
      probabilistic models, the realistic classification of local communities subject
      to their diversity and species dynamics is proposed with respect to the
      immigration probability, the species metacommunity relative abundance, and the
      size of local community.

PMID- 17025468
TI  - How does a protein search for the specific site on DNA: The role of disorder.
AB  - Proteins can locate their specific targets on DNA up to two orders of magnitude
      faster than the Smoluchowski three-dimensional diffusion rate. This happens due
      to nonspecific adsorption of proteins to DNA and subsequent one-dimensional
      sliding along DNA. We call such a one-dimensional route towards the target an
      "antenna." We studied the role of the dispersion of nonspecific binding energies
      within the antenna due to a quasirandom sequence of natural DNA. A random energy
      profile for sliding proteins slows the searching rate for the target. We show
      that this slowdown is different for macroscopic and mesoscopic antennas.

PMID- 17025470
TI  - Stochasticity and evolutionary stability.
AB  - In stochastic dynamical systems, different concepts of stability can be obtained
      in different limits. A particularly interesting example is evolutionary game
      theory, which is traditionally based on infinite populations, where strict Nash
      equilibria correspond to stable fixed points that are always evolutionarily
      stable. However, in finite populations stochastic effects can drive the system
      away from strict Nash equilibria, which gives rise to a new concept for
      evolutionary stability. The conventional and the new stability concepts may
      apparently contradict each other leading to conflicting predictions in large yet
      finite populations. We show that the two concepts can be derived from the
      frequency dependent Moran process in different limits. Our results help to
      determine the appropriate stability concept in large finite populations. The
      general validity of our findings is demonstrated showing that the same results
      are valid employing vastly different co-evolutionary processes.

PMID- 17025469
TI  - Membrane electroporation: The absolute rate equation and nanosecond time scale
      pore creation.
AB  - The recent applications of nanosecond, megavolt-per-meter electric field pulses
      to biological systems show striking cellular and subcellular electric field
      induced effects and revive the interest in the biophysical mechanism of
      electroporation. We first show that the absolute rate theory, with experimentally
      based parameter input, is consistent with membrane pore creation on a nanosecond
      time scale. Secondly we use a Smoluchowski equation-based model to formulate a
      self-consistent theoretical approach. The analysis is carried out for a planar
      cell membrane patch exposed to a 10 ns trapezoidal pulse with 1.5 ns rise and
      fall times. Results demonstrate reversible supraelectroporation behavior in terms
      of transmembrane voltage, pore density, membrane conductance, fractional aqueous
      area, pore distribution, and average pore radius. We further motivate and justify
      the use of Krassowska's asymptotic electroporation model for analyzing nanosecond
      pulses, showing that pore creation dominates the electrical response and that
      pore expansion is a negligible effect on this time scale.

PMID- 17025471
TI  - Lattice-gas model of DNA charge inversion by a positively charged
      polyelectrolyte.
AB  - The model of DNA charge inversion by Nguyen and Shklovskii [T. T. Nguyen and B.
      I. Shklovskii, Phys. Rev. Lett. 89, 018101 (2002)] is extended. A single double
      helix strand of DNA is represented by a lattice of negative charges at the
      positions of the protruding oxygens of the phosphates along the DNA backbone, and
      the adsorbed polyelectrolyte molecules are represented by charged dimers. A
      lattice-gas model is used in which dimers adsorbing either parallel or
      perpendicular to the lattice are treated as separate species, and the model
      allows for vacancies between adsorbed species. The mean field theory used is
      formulated as a saddle-point approximation of the exact functional integral
      representation of the grand canonical partition function, opening the way for the
      inclusion of the effects of charge fluctuation corrections.

PMID- 17025472
TI  - Numerical study of a microscopic artificial swimmer.
AB  - We present a detailed numerical study of a microscopic artificial swimmer
      realized recently by Dreyfus in experiments [Dreyfus, Nature 437, 862 (2005)]. It
      consists of an elastic filament composed of superparamagnetic particles that are
      linked together by DNA strands. Attached to a load particle, the resulting
      swimmer is actuated by an oscillating external magnetic field so that it performs
      a nonreciprocal motion in order to move forward. We model the superparamagnetic
      filament by a bead-spring configuration that resists bending like a rigid rod and
      whose beads experience friction with the surrounding fluid and hydrodynamic
      interactions with each other. We show that, aside from finite-size effects, its
      dynamics is governed by the dimensionless sperm number, the magnitude of the
      magnetic field, and the angular amplitude of the field's oscillating direction.
      Then we study the mean velocity and the efficiency of the swimmer as a function
      of these parameters and the size of the load particle. In particular, we clarify
      that the real velocity of the swimmer is influenced by two main factors, namely
      the shape of the beating filament (determined by the sperm number and the
      magnetic-field strength) and the oscillation frequency. Furthermore, the load
      size influences the performance of the swimmer and has to be chosen as a
      compromise between the largest swimming velocity and the best efficiency.
      Finally, we demonstrate that the direction of the swimming velocity changes in a
      symmetry-breaking transition when the angular amplitude of the field's
      oscillating direction is increased, in agreement with experiments.

PMID- 17025473
TI  - Force generation in small ensembles of Brownian motors.
AB  - The motility of certain gram-negative bacteria is mediated by retraction of type
      IV pili surface filaments, which are essential for infectivity. The retraction is
      powered by a strong molecular motor protein, PilT, producing very high forces
      that can exceed 150 pN. The molecular details of the motor mechanism are still
      largely unknown, while other features have been identified, such as the ring
      shaped protein structure of the PilT motor. The surprisingly high forces
      generated by the PilT system motivate a model investigation of the generation of
      large forces in molecular motors. We propose a simple model, involving a small
      ensemble of motor subunits interacting through the deformations on a circular
      backbone with finite stiffness. The model describes the motor subunits in terms
      of diffusing particles in an asymmetric, time-dependent binding potential
      (flashing ratchet potential), roughly corresponding to the ATP hydrolysis cycle.
      We compute force-velocity relations in a subset of the parameter space and
      explore how the maximum force (stall force) is determined by stiffness, binding
      strength, ensemble size, and degree of asymmetry. We identify two qualitatively
      different regimes of operation depending on the relation between ensemble size
      and asymmetry. In the transition between these two regimes, the stall force
      depends nonlinearly on the number of motor subunits. Compared to its constituents
      without interactions, we find higher efficiency and qualitatively different force
      velocity relations. The model captures several of the qualitative features
      obtained in experiments on pilus retraction forces, such as roughly constant
      velocity at low applied forces and insensitivity in the stall force to changes in
      the ATP concentration.

PMID- 17025474
TI  - Traveling waves in coupled reaction-diffusion models with degenerate sources.
AB  - We consider a general system of coupled nonlinear diffusion equations that are
      characterized by having degenerate source terms and thereby not having isolated
      rest states. Using a general form of physically relevant source terms, we derive
      conditions that are required to trigger traveling waves when a stable uniform
      steady-state solution is perturbed by a highly localized disturbance. We show
      that the degeneracy in the source terms implies that traveling waves have a
      number of surprising properties that are not present for systems with
      nondegenerate source terms. We also show that such systems can lead to a pair of
      waves that initially propagate outwards from the disturbance, slow down, and
      reverse direction before ultimately colliding and annihilating each other.

PMID- 17025475
TI  - Thermodynamic behavior of a phase transition in a model for sympatric speciation.
AB  - We investigate the macroscopic effects of the ingredients that drive the origin
      of species through sympatric speciation. In our model, sympatric speciation is
      obtained as we tune up the strength of competition between individuals with
      different phenotypes. As a function of this control parameter, we can
      characterize, through the behavior of a macroscopic order parameter, a phase
      transition from a nonspeciation to a speciation state of the system. The behavior
      of the first derivative of the order parameter with respect to the control
      parameter is consistent with a phase transition and exhibits a sharp peak at the
      transition point. For different resources distribution, the transition point is
      shifted, an effect similar to pressure in a PVT system. The inverse of the
      parameter related to a sexual selection strength behaves like an external field
      in the system and, as thus, is also a control parameter. The macroscopic effects
      of the biological parameters used in our model are a reminiscent of the behavior
      of thermodynamic quantities in a phase transition of an equilibrium physical
      system.

PMID- 17025476
TI  - Power laws in microrheology experiments on living cells: Comparative analysis and
      modeling.
AB  - We compare and synthesize the results of two microrheological experiments on the
      cytoskeleton of single cells. In the first one, the creep function J(t) of a cell
      stretched between two glass plates is measured after applying a constant force
      step. In the second one, a microbead specifically bound to transmembrane
      receptors is driven by an oscillating optical trap, and the viscoelastic
      coefficient Ge(omega) is retrieved. Both J(t) and Ge(omega) exhibit power law
      behaviors: J(t) = A0(t/t0)alpha and absolute value (Ge(omega)) =
      G0(omega/omega0)alpha, with the same exponent alpha approximately 0.2. This power
      law behavior is very robust; alpha is distributed over a narrow range, and shows
      almost no dependence on the cell type, on the nature of the protein complex which
      transmits the mechanical stress, nor on the typical length scale of the
      experiment. On the contrary, the prefactors A0 and G0 appear very sensitive to
      these parameters. Whereas the exponents alpha are normally distributed over the
      cell population, the prefactors A0 and G0 follow a log-normal repartition. These
      results are compared with other data published in the literature. We propose a
      global interpretation, based on a semiphenomenological model, which involves a
      broad distribution of relaxation times in the system. The model predicts the
      power law behavior and the statistical repartition of the mechanical parameters,
      as experimentally observed for the cells. Moreover, it leads to an estimate of
      the largest response time in the cytoskeletal network: tau(m) approximately 1000
      s.

PMID- 17025477
TI  - Large-scale oscillation of structure-related DNA sequence features in human
      chromosome 21.
AB  - Human chromosome 21 is the only chromosome in the human genome that exhibits
      oscillation of the (G+C) content of a cycle length of hundreds kilobases (kb) (
      500 kb near the right telomere). We aim at establishing the existence of a
      similar periodicity in structure-related sequence features in order to relate
      this (G+C)% oscillation to other biological phenomena. The following quantities
      are shown to oscillate with the same 500 kb periodicity in human chromosome 21:
      binding energy calculated by two sets of dinucleotide-based thermodynamic
      parameters, AA/TT and AAA/TTT bi- and tri-nucleotide density, 5'-TA-3'
      dinucleotide density, and signal for 10- or 11-base periodicity of AA/TT or
      AAA/TTT. These intrinsic quantities are related to structural features of the
      double helix of DNA molecules, such as base-pair binding, untwisting or
      unwinding, stiffness, and a putative tendency for nucleosome formation.

PMID- 17025478
TI  - Informational structure of two closely related eukaryotic genomes.
AB  - Attempts to identify a species on the basis of its DNA sequence on purely
      statistical grounds have been formulated for more than a decade. The most
      prominent of such genome signatures relies on neighborhood correlations (i.e.,
      dinucleotide frequencies) and, consequently, attributes species identification to
      mechanisms operating on the dinucleotide level (e.g., neighbor-dependent
      mutations). For the examples of Mus musculus and Rattus norvegicus we analyze
      short- and intermediate-range statistical correlations in DNA sequences. These
      correlation profiles are computed for all chromosomes of the two species. We find
      that with increasing range of correlations the capacity to distinguish between
      the species on the basis of this correlation profile is getting better and
      requires ever shorter sequence segments for obtaining a full species separation.
      This finding suggests that distinctive traits within the sequence are situated
      beyond the level of few nucleotides. The large-scale statistical patterning of
      DNA sequences on which such genome signatures are based is thus substantially
      determined by mobile elements (e.g., transposons and retrotransposons). The study
      and interspecies comparison of such correlation profiles can, therefore, reveal
      features of retrotransposition, segmental duplications, and other processes of
      genome evolution.

PMID- 17025479
TI  - Conformational transformations induced by the charge-curvature interaction: Mean
      field approach.
AB  - A simple phenomenological model for describing the conformational dynamics of
      biological macromolecules via the nonlinearity-induced instabilities is proposed.
      It is shown that the interaction between charges and bending degrees of freedom
      of closed molecular aggregates may act as drivers giving impetus to
      conformational dynamics of biopolymers. It is demonstrated that initially
      circular aggregates may undergo transformation to polygonal shapes and possible
      application to aggregates of bacteriochlorophyl a molecules is considered.

PMID- 17025480
TI  - Signaling between cells attached to a surface.
AB  - We present a kinetic model allowing one to classify likely scenarios of protein
      mediated communication between attached cells of two distinct types. In our
      treatment, messenger proteins, synthesized in type-1 cells, are considered to
      penetrate the external membrane of these cells, diffuse in the extracellular
      medium, associate with the receptors in the external membrane of cells of both
      types, and induce intracellular signal transduction cascades, influencing the
      development of cells. Protein degradation inside and outside cells is taken into
      account as well.

PMID- 17025481
TI  - Fluctuation-induced interactions between domains in membranes.
AB  - We study a model lipid bilayer composed of a mixture of two incompatible lipid
      types which have a natural tendency to segregate in the absence of membrane
      fluctuations. The membrane is mechanically characterized by a local bending
      rigidity kappa(phi) which varies with the average local lipid composition phi. We
      show, in the case where kappa varies weakly with phi, that the effective
      interaction between lipids of the same type either can be everywhere attractive
      or can have a repulsive component at intermediate distances greater than the
      typical lipid size. When this interaction has a repulsive component, it can
      prevent macrophase separation and lead to separation in mesophases with a finite
      domain size. This effect could be relevant to certain experimental and numerical
      observations of mesoscopic domains in such systems.

PMID- 17025482
TI  - Bursting induced by excitatory synaptic coupling in nonidentical conditional
      relaxation oscillators or square-wave bursters.
AB  - This work explains a mechanism through which the introduction of excitatory
      synaptic coupling between two model cells, one of which is excitable and the
      other of which is tonically active when uncoupled, leads to bursting in the
      resulting two-cell network. This phenomenon can arise when the individual cells
      are conditional relaxation oscillators, in that they can be tuned to engage in
      relaxation oscillations, or when they are conditional square-wave bursters. The
      mechanism is illustrated with a model for conditional pacemaker neurons in the
      pre-Botzinger complex as well as with a reduced form of this model. In the
      relaxation oscillator case, a periodic bursting solution is proved to exist in
      the singular limit, under a pair of general conditions. These conditions relate
      the durations of the silent and active phases of the bursting solution to the
      locations of certain structures in the phase plane, at appropriate synaptic input
      strengths. Further, additional conditions on the relative flow rates in the
      silent and active phases are proved to imply the uniqueness and asymptotic
      stability of the bursting solution.

PMID- 17025484
TI  - Absorption and scattering perturbations in homogeneous and layered diffusive
      media probed by time-resolved reflectance at null source-detector separation.
AB  - We characterize the capability of time-resolved reflectance measurements at small
      source-detector separation (less than 5 mm) to localize small inhomogeneities
      embedded in an otherwise homogeneous or layered diffusive medium. By considering
      both absorption and scattering inhomogeneities, we demonstrate the improvement of
      this approach in terms of contrast and spatial resolution, as compared to more
      typical set-ups involving larger source-detection separations (few centimeters).
      Simulations are performed exploiting an analytical perturbation approach to
      diffusion theory and a four-layer heterogeneous time-resolved Monte Carlo code,
      considering realistic tissue geometries. Exhaustive investigation in the
      parameters space is reported.

PMID- 17025483
TI  - Stress, birefringence, and conformational relaxation of an initially straight
      stiff bead-rod polymer.
AB  - The stress and optical relaxation of an initially straight stiff polymer chain
      are studied through Brownian dynamics simulations (based on a semiflexible bead
      rod model) covering a broad range of time scales and polymer lengths. The strong
      stress component sigma11 (where "1" is the direction of the original alignment)
      is shown to be associated with the chain's longitudinal relaxation while the weak
      stress component sigma22 = sigma33 is shown to depend on the chain's transverse
      relaxation. The two independent stress components follow a different relaxation;
      this anisotropy is shown to result from the participation of the different
      relaxation modes in the transverse direction. The chain's optical relaxation is
      shown to be affected by the longitudinal dynamics only. The early relaxation of
      the strong stress component sigma11 and that of the chain's optical properties
      constitute a universal behavior--i.e., valid for any stiffness of the bead-rod
      chain, since at the early times the bending forces do not affect the longitudinal
      dynamics. Based on the knowledge of the physical mechanism and the chain's
      conformational behavior, we predict and explain the polymer stress and optical
      relaxation. A nonlinear stress-optic law (valid for any time and chain stiffness)
      is derived based on the identified relation of the chain configuration with the
      optical properties and the polymer stress. A coarse-grain model describing
      extended semiflexible bead road chains is also derived.

PMID- 17025485
TI  - Dynamics of a nonconserving Davydov monomer.
AB  - The Davydov-Scott model describes the transfer of energy along hydrogen-bonded
      chains, like those that stabilize the structure of alpha helices. It is based on
      the hypothesis that amide I excitations are created (by the hydrolysis of ATP,
      for instance) and kept in the system. Recent experimental results confirm that
      the energy associated with amide I excitations does indeed last for tens of
      picoseconds in proteins and model systems. However, the Davydov-Scott model
      cannot describe the conversion of that energy into work, because it conserves the
      number of excitations. With the aim of describing conformational changes, we
      consider, in this paper, a nonconserving generalization of the model, which is
      found to describe essentially a contraction of the hydrogen bond adjacent to the
      site where an excitation is present. Unlike the one-site Davydov-Scott model,
      that contraction is time dependent because the number of excitations is not
      conserved. However, considering the time average of the dynamical variables, the
      results reported here tend to the known results of the Davydov-Scott model.

PMID- 17025486
TI  - Solitons in the Yakushevich model of DNA beyond the contact approximation.
AB  - The Yakushevich model of DNA torsion dynamics supports soliton solutions, which
      are supposed to be of special interest for DNA transcription. In the discussion
      of the model, one usually adopts the approximation l0 --> 0, where l0 is a
      parameter related to the equilibrium distance between bases in a Watson-Crick
      pair. Here we analyze the Yakushevich model without l0 --> 0. The model still
      supports soliton solutions indexed by two winding numbers (n,m); we discuss in
      detail the fundamental solitons, corresponding to winding numbers (1,0) and (0,1)
      respectively.

PMID- 17025488
TI  - Boltzmann and hydrodynamic description for self-propelled particles.
AB  - We study analytically the emergence of spontaneous collective motion within large
      bidimensional groups of self-propelled particles with noisy local interactions, a
      schematic model for assemblies of biological organisms. As a central result, we
      derive from the individual dynamics the hydrodynamic equations for the density
      and velocity fields, thus giving a microscopic foundation to the phenomenological
      equations used in previous approaches. A homogeneous spontaneous motion emerges
      below a transition line in the noise-density plane. Yet, this state is shown to
      be unstable against spatial perturbations, suggesting that more complicated
      structures should eventually appear.

PMID- 17025487
TI  - Gleaming and dull surface textures from photonic-crystal-type nanostructures in
      the butterfly Cyanophrys remus.
AB  - Photonic-crystal-type nanostructures occurring in the scales of the butterfly
      Cyanophrys remus were investigated by optical and electron microscopy (scanning
      and transmission electron microscopy), reflectance measurements (specular,
      integrated, and goniometric), by fast Fourier transform analysis of micrographs,
      by modeling, and by numerical simulation of the measured reflectance data. By
      evaluating the collected data in a cross-correlated way, we show that the
      metallic blue dorsal coloration originates from scales which individually are
      photonic single crystals of 50 x 120 microm2 , while the matt pea-green
      coloration of the ventral side arises from the cumulative effect of randomly
      arranged, bright photonic crystallites (blue, green, and yellow) with typical
      diameters in the 3-10-mum range. Both structures are based on a very moderate
      refractive index contrast between air and chitin. Using a bleached specimen in
      which the pigment has decayed with time, we investigated the role of pigment in
      photonic-crystal material in the process of color generation. The possible
      biologic utility of the metallic blue (single-crystal) and dull green
      (polycrystal) textures both achieved with photonic crystals are briefly
      discussed. Potential applications in the field of colorants, flat panel displays,
      smart textiles, and smart papers are surveyed.

PMID- 17025489
TI  - Stochastic resonance in a linear system: An exact solution.
AB  - Multistable systems can exhibit stochastic resonance which is characterized by
      the amplification of small periodic signals by additive noise. Here we consider a
      nonmultistable linear system with a multiplicative noise forced by an external
      periodic signal. The noise is the sum of a colored noise of mean value zero and a
      noise with a definite sign. We show that the system exhibits stochastic resonance
      through the numerical study of an exact analytical expression for the mean value
      obtained by functional integral techniques. This is proof of the effect for a
      very general kind of noise which can even have a definite sign.

PMID- 17025490
TI  - Ionic contribution to the electric current in an electrolytic cell submitted to
      an external voltage.
AB  - The ionic contribution to the electrical current in an electrolytic cell
      submitted to an external voltage linearly increasing with the time is evaluated.
      The investigation is performed in the limit of small and large electric field, in
      which the density of ions depends on the actual electric field in the sample. In
      the analysis, it is assumed that the ionic separation induced by an external
      field can be described by a surface density of charge. We show that the ions are
      responsible for a peak in the current, followed by a delay in the application of
      the external voltage. From the analysis of the peak and its delay, it is possible
      to obtain information on the density of ions in thermodynamical equilibrium, and
      on the mobility of the ions in the considered liquid.

PMID- 17025491
TI  - Orientational transition in a nematic liquid crystal at a patterned surface.
AB  - We consider a semi-infinite nematic in contact with a periodic patterned surface
      with alternate planar and homeotropic stripes. Extending the work of Barbero, we
      find the free energy (assuming K1 = K3) for the situations where the easy
      direction on the planar stripe is either perpendicular or parallel to the length
      of the stripes. We find the bulk free energy difference between the structures to
      be proportional to square root(K2/K1) and so we consider the possibility of a
      spontaneous transition between the two states if the azimuthal anchoring energy
      is sufficiently weak and K1 not equal K2. We compute the critical azimuthal
      anchoring energy for such a transition in terms of the relative width of the
      stripes and the period of the pattern and find it to be approximately 10(-6) J m(
      2), comparable to experimental values.

PMID- 17025492
TI  - Quasiperiodic property in Alu repeats.
AB  - We investigate the possible quasiperiodic property in the sequences of Alu
      repeats, one of typical noncoding DNA sequences. We calculated the quasiperiods
      of the right and left monomers of Alu repeats of different families with
      quasiperiodic matrix algorithm. It is interesting that the right monomers of all
      families show significant quasiperiod 8 in their sequences while the left
      monomers show quasiperiods 8 or 5. Our results indicate that there exist common
      quasiperiods in most Alu repeats. This may be helpful to further explore possible
      functions of Alu repeats.

PMID- 17025493
TI  - Comment on "Precise domain specification in the developing Drosophila embryo".
AB  - In a recent paper, Houchmandzadeh [Phys. Rev. E 72, 061920 (2005)] introduce a
      correlated bigradient model in order to explain the robust scaling of the
      boundary of hunchback (hb) expression in the early Drosophila embryo. In
      particular, they stress that recent experiments by Lucchetta [Nature (London)
      434, 1134 (2005)], where embryos whose anterior and posterior halves develop at
      different temperatures still show excellent precision in the hb boundary, are in
      good agreement with such a model. We would like to show here that this conclusion
      is unwarranted. This is because the experiments of Lucchetta were done at
      different temperatures from those studied in the model. Since in other
      temperature combinations the model does not produce precise boundaries and there
      are no systematic trends in these deviations, a comparison to the experiment is
      not possible. Furthermore, we would like to point out that any correlated
      bigradient model should also take into account the fluctuations of the bicoid
      profile within an embryo. When forming correlated bigradients of experimental
      profiles from an online library, we observe that these intraembryo variations
      destroy robustness of the hb boundary even in the wild-type situation.

PMID- 17025494
TI  - Multiscale mixing efficiencies for steady sources.
AB  - Multiscale mixing efficiencies for passive scalar advection are defined in terms
      of the suppression of variance weighted at various length scales. We consider
      scalars maintained by temporally steady but spatially inhomogeneous sources,
      stirred by statistically homogeneous and isotropic incompressible flows including
      fully developed turbulence. The mixing efficiencies are rigorously bounded in
      terms of the Peclet number and specific quantitative features of the source.
      Scaling exponents for the bounds at high Peclet number depend on the spectrum of
      length scales in the source, indicating that molecular diffusion plays a more
      important quantitative role than that implied by classical eddy diffusion
      theories.

PMID- 17025495
TI  - Relevance of dynamic wetting in viscous fingering patterns.
AB  - We demonstrate that wetting effects at moving contact lines have a strong impact
      in viscous fingering patterns. Experiments in a rotating Hele-Shaw (HS) cell, dry
      or prewetted, show consistent morphological differences. When the wetting fluid
      invades a dry region, contact angle dynamics yield a kinetic contribution to the
      interface pressure drop that scales with capillary number as Ca(2/3) but is
      significantly larger than the Park-Homsy kinetic correction. Numerical results
      are in very good agreement with experiments and show that standard HS equations
      work best for prewetted cells.

PMID- 17025496
TI  - Radiative opacity of gold plasmas studied by a detailed level-accounting method.
AB  - There are systematic discrepancies unexplained so far between theory and
      experiment for opacities of mid- and high- Z plasmas. To address this issue, we
      investigated the radiative opacity of gold plasmas by using a detailed level
      accounting (DLA) method, in which various physical effects can be taken into
      account. In this work, we studied in detail the effects of core-valence electron
      correlation and linewidth on the opacity of gold plasmas. Our DLA results
      correctly explain the relative intensity of the two strong absorption peaks
      located near the photon energies of 70 and 80eV , which was experimentally
      observed by Eidmann [Europhys. Lett. 44, 459 (1998)]. Meanwhile, the DLA results
      showed that effects of saturation for the strong individual lines are evident in
      the transmission spectrum.

PMID- 17025497
TI  - Fixed-mass multifractal analysis of river networks and braided channels.
AB  - A fixed-mass multifractal (FMA) analysis was used to investigate natural river
      networks and braided channels. In particular, while the study of natural river
      networks was performed with fixed-size algorithms (FSAs) in the past, the
      analysis of natural braided channels was not pursued before to our knowledge.
      Results showed the multifractal and non-plane-filling nature of all the
      digitalized data sets. Analysis of the digitalization step (constant or not) was
      performed and showed that it does not exert a strong influence on the assessed
      values of the Lipschitz-Holder exponents and the support dimensions, even if a
      constant step permits better reconstruction of the right sides of the spectra,
      for negative moment orders of probabilities. The FMA approach presented two
      improvements with respect to the FSA one, in terms of oscillations of the scaling
      curves for negative moment orders of probabilities and of error bars. A more
      precise assessment of the multifractal spectra is of great importance in the
      development of multifractal models for the simulation of flood hydrographs.

PMID- 17025498
TI  - Network properties of written human language.
AB  - We investigate the nature of written human language within the framework of
      complex network theory. In particular, we analyze the topology of Orwell's "1984"
      focusing on the local properties of the network, such as the properties of the
      nearest neighbors and the clustering coefficient. We find a composite power law
      behavior for both the average nearest neighbor's degree and average clustering
      coefficient as a function of the vertex degree. This implies the existence of
      different functional classes of vertices. Furthermore, we find that the second
      order vertex correlations are an essential component of the network architecture.
      To model our empirical results we extend a previously introduced model for
      language due to Dorogovtsev and Mendes. We propose an accelerated growing network
      model that contains three growth mechanisms: linear preferential attachment,
      local preferential attachment, and the random growth of a predetermined small
      finite subset of initial vertices. We find that with these elementary stochastic
      rules we are able to produce a network showing syntacticlike structures.

PMID- 17025499
TI  - Learning about knowledge: a complex network approach.
AB  - An approach to modeling knowledge acquisition in terms of walks along complex
      networks is described. Each subset of knowledge is represented as a node, and
      relations between such knowledge are expressed as edges. Two types of edges are
      considered, corresponding to free and conditional transitions. The latter case
      implies that a node can only be reached after visiting previously a set of nodes
      (the required conditions). The process of knowledge acquisition can then be
      simulated by considering the number of nodes visited as a single agent moves
      along the network, starting from its lowest layer. It is shown that hierarchical
      networks--i.e., networks composed of successive interconnected layers--are
      related to compositions of the prerequisite relationships between the nodes. In
      order to avoid deadlocks--i.e., unreachable nodes--the subnetwork in each layer
      is assumed to be a connected component. Several configurations of such
      hierarchical knowledge networks are simulated and the performance of the moving
      agent quantified in terms of the percentage of visited nodes after each movement.
      The Barabasi-Albert and random models are considered for the layer and
      interconnecting subnetworks. Although all subnetworks in each realization have
      the same number of nodes, several interconnectivities, defined by the average
      node degree of the interconnection networks, have been considered. Two visiting
      strategies are investigated: random choice among the existing edges and
      preferential choice to so far untracked edges. A series of interesting results
      are obtained, including the identification of a series of plateaus of knowledge
      stagnation in the case of the preferential movement strategy in the presence of
      conditional edges.

PMID- 17025500
TI  - Models and average properties of scale-free directed networks.
AB  - We extend the merging model for undirected networks by Kim [Eur. Phys. J. B 43,
      369 (2004)] to directed networks and investigate the emerging scale-free
      networks. Two versions of the directed merging model, friendly and hostile
      merging, give rise to two distinct network types. We uncover that some nontrivial
      features of these two network types resemble two levels of a certain
      randomization/nonspecificity in the link reshuffling during network evolution.
      Furthermore, the same features show up, respectively, in metabolic networks and
      transcriptional networks. We introduce measures that single out the
      distinguishing features between the two prototype networks, as well as point out
      features that are beyond the prototypes.

PMID- 17025501
TI  - Crack surface roughness in three-dimensional random fuse networks.
AB  - Using large system sizes with extensive statistical sampling, we analyze the
      scaling properties of crack roughness and damage profiles in the three
      dimensional random fuse model. The analysis of damage profiles indicates that
      damage accumulates in a diffusive manner up to the peak load, and localization
      sets in abruptly at the peak load, starting from a uniform damage landscape. The
      global crack width scales as W approximately L(0.5) and is consistent with the
      scaling of localization length xi approximately L(0.5) used in the data collapse
      of damage profiles in the postpeak regime. This consistency between the global
      crack roughness exponent and the postpeak damage profile localization length
      supports the idea that the postpeak damage profile is predominantly due to the
      localization produced by the catastrophic failure, which at the same time results
      in the formation of the final crack. Finally, the crack width distributions can
      be collapsed for different system sizes and follow a log-normal distribution.

PMID- 17025502
TI  - Fluctuation relations for a driven Brownian particle.
AB  - We consider a driven Brownian particle, subject to both conservative and
      nonconservative applied forces, whose probability evolves according to the
      Kramers equation. We derive a general fluctuation relation, expressing the ratio
      of the probability of a given Brownian path in phase space with that of the time
      reversed path, in terms of the entropy flux to the heat reservoir. This
      fluctuation relation implies those of Seifert, Jarzynski, and Gallavotti-Cohen in
      different special cases.

PMID- 17025503
TI  - Inwardly rotating spiral wave breakup in oscillatory reaction-diffusion media.
AB  - The breakup of inwardly rotating spiral waves has been investigated in an
      oscillatory reaction-diffusion system near a Hopf bifurcation point. The breakup
      first occurred at the region far away from the core area, then gradually involved
      the whole medium by increasing the diffusion coefficient ratio between the two
      components of the oscillator system. With the approximation of the Complex
      Ginzburg-Landau equation (CGLE), the criteria for the occurrence of the inwardly
      rotating spiral wave are examined theoretically. The analysis of the stability in
      the corresponding CGLE revealed that the breakup of the inward spiral wave was
      related to the Eckhaus instability.

PMID- 17025504
TI  - Statistical mechanics of lossy compression using multilayer perceptrons.
AB  - Statistical mechanics is applied to lossy compression using multilayer
      perceptrons for unbiased Boolean messages. We utilize a treelike committee
      machine (committee tree) and treelike parity machine (parity tree) whose transfer
      functions are monotonic. For compression using a committee tree, a lower bound of
      achievable distortion becomes small as the number of hidden units K increases.
      However, it cannot reach the Shannon bound even where K-->infinity. For a
      compression using a parity tree with K> or =2 hidden units, the rate distortion
      function, which is known as the theoretical limit for compression, is derived
      where the code length becomes infinity.

PMID- 17025505
TI  - Essence of conservation forms in the traveling wave solutions of higher-order
      traffic flow models.
AB  - This paper shows the essence of conservation forms when applying the weak
      solution theory to solve the traveling wave solution of a wide cluster in the
      Payne-Whitham (PW) model. The consideration of the conservation form for the
      acceleration equation is an important ingredient in the development of higher
      order traffic flow models, but it is largely ignored in the research community.
      To fix the idea, we define two conservation forms for the same PW model, and
      consequently derive two solutions with different sets of characteristic
      parameters of the wide cluster. The analytical results are in good agreement with
      those that are obtained from numerical simulations. Moreover, these two solutions
      are also shown to be asymptotic to those of the well-known Kuhne and Kerner
      Konhauser models with a viscosity term. More importantly, the careful treatment
      of the conservation form for the acceleration equation closes the important gap
      in the literature. Without the conservation form, the solution obtained depends
      very much on the design of numerical schemes, and can be quite arbitrary and may
      not adequately conform to the physically relevant properties.

PMID- 17025506
TI  - Logarithmic relaxation due to minimization of interactions in the Burridge
      Knopoff model.
AB  - The time evolution of macroscopic quantities describing the relaxation of complex
      systems often contains a domain with logarithmic time dependence. This
      logarithmic behavior at the macroscopic level is often associated with strongly
      interacting elements at the microscopic level, whose interactions depend
      significantly on their history. In this paper we show that stress relaxation in
      the Burridge-Knopoff (BK) model of multicontact friction behaves logarithmically,
      when the model is in, or close to, the solitary state where the elements move
      independently. For this regime we present an automaton that allows us to follow
      the decay of stress relaxation over the entire range where it behaves
      logarithmically in time. We show that our model can be mapped onto a system of
      noninteracting elements subject to a uniform distribution of forces, for which
      logarithmic stress relaxation is derived analytically.

PMID- 17025507
TI  - Contact of single asperities with varying adhesion: comparing continuum mechanics
      to atomistic simulations.
AB  - Atomistic simulations are used to test the equations of continuum contact
      mechanics in nanometer scale contacts. Nominally spherical tips, made by bending
      crystals or cutting crystalline or amorphous solids, are pressed into a flat,
      elastic substrate. The normal displacement, contact radius, stress distribution,
      friction, and lateral stiffness are examined as a function of load and adhesion.
      The atomic scale roughness present on any tip made of discrete atoms is shown to
      have profound effects on the results. Contact areas, local stresses, and the work
      of adhesion change by factors of 2 to 4, and the friction and lateral stiffness
      vary by orders of magnitude. The microscopic factors responsible for these
      changes are discussed. The results are also used to test methods for analyzing
      experimental data with continuum theory to determine information, such as contact
      area, that cannot be measured directly in nanometer scale contacts. Even when the
      data appear to be fit by continuum theory, extracted quantities can differ
      substantially from their true values.

PMID- 17025508
TI  - Energy dissipation and fluctuation response for particles in fluids.
AB  - An equality was recently proved relating energy dissipation to the difference of
      the response and velocity correlation functions for a class of Langevin
      equations. We generalize this for the physically important case of particles in a
      fluid, where bath fluctuations are nonlocal in time due to hydrodynamic modes. We
      also show that the inclusion of a mass term does not alter the result and provide
      a simple physical interpretation of the original equality.

PMID- 17025509
TI  - Complex earthquake networks: hierarchical organization and assortative mixing.
AB  - To characterize the dynamical features of seismicity as a complex phenomenon, the
      seismic data are mapped to a growing random graph, which is a small-world scale
      free network. Here, hierarchical and mixing properties of such a network are
      studied. The clustering coefficient is found to exhibit asymptotic power-law
      decay with respect to connectivity, showing hierarchical organization. This
      structure is supported by not only main shocks but also small shocks, and may
      have its origin in the combined effect of vertex fitness and deactivation by
      stress release at faults. The nearest-neighbor average connectivity and the
      Pearson correlation coefficient are also calculated. It is found that the
      earthquake network has assortative mixing. This is a main difference of the
      earthquake network from the Internet with disassortative mixing. Physical
      implications of these results are discussed.

PMID- 17025510
TI  - Dynamic behaviors in directed networks.
AB  - Motivated by the abundance of directed synaptic couplings in a real biological
      neuronal network, we investigate the synchronization behavior of the Hodgkin
      Huxley model in a directed network. We start from the standard model of the Watts
      Strogatz undirected network and then change undirected edges to directed arcs
      with a given probability, still preserving the connectivity of the network. A
      generalized clustering coefficient for directed networks is defined and used to
      investigate the interplay between the synchronization behavior and underlying
      structural properties of directed networks. We observe that the directedness of
      complex networks plays an important role in emerging dynamical behaviors, which
      is also confirmed by a numerical study of the sociological game theoretic voter
      model on directed networks.

PMID- 17025511
TI  - Packet traffic analysis of scale-free networks for large-scale network-on-chip
      design.
AB  - Recent progress in integrated circuit technologies requires precise evaluation
      between dynamic characteristics and topological architecture design. In this
      paper, we have investigated the performance evaluation of network-on-chip (NoC)
      architectures constructed with diverse scale-free network topologies by dynamic
      packet traffic simulation and theoretical network analysis. Topological
      differences of scale-free networks are evaluated by the degree-degree
      correlations that indicate topological tendency between the degree of a node and
      that of the nearest neighbors. Our simulation results quantitatively show that
      the NoC architecture constructed with the topology where hubs mostly connect to
      lower-degree nodes is found to achieve short latency and low packet loss ratio
      since it can disperse traffic load and avoid the extreme concentration of load on
      hubs.

PMID- 17025512
TI  - Interplay between function and structure in complex networks.
AB  - We show that abrupt structural transitions can arise in functionally optimal
      networks, driven by small changes in the level of transport congestion. Our
      results offer an explanation as to why so many diverse species of network
      structure arise in nature (e.g., fungal systems) under essentially the same
      environmental conditions. Our findings are based on an exactly solvable model
      system which mimics a variety of biological and social networks. We then extend
      our analysis by introducing a renormalization scheme involving cost motifs, to
      describe analytically the average shortest path across multiple-ring-and-hub
      networks. As a consequence, we uncover a "skin effect" whereby the structure of
      the inner multi-ring core can cease to play any role in terms of determining the
      average shortest path across the network.

PMID- 17025513
TI  - Diffusion accelerates and enhances chirality selection.
AB  - The diffusion effect on chirality selection in a two-dimensional reaction
      diffusion model is studied by Monte Carlo simulations. The model consists of
      achiral reactants A which turn into either of the chiral products R or S in a
      solvent of chemically inactive vacancies V . The reaction contains a nonlinear
      autocatalysis as well as a recycling process, and the chiral symmetry breaking is
      monitored by an enantiomeric excess (ee) phi. Without dilution a strong nonlinear
      autocatalysis ensures chiral symmetry breaking. By diluting a diffusionless
      system, the ee phi decreases and a racemic state is recovered below a critical
      concentration c(c) . When the diffusion is allowed, the steady value of phi
      increases and c(c) decreases. As for the relation between the ee phi and the
      concentration c , a formula interpolating between the diffusionless (D=0) and the
      homogeneous (D=infinity) limits is proposed by incorporating the diffusional
      enhancement of the concentrations of chiral species. Diffusion also accelerates
      the development of the chiral order, and the time required to establish the order
      in a system of a size L(2) is inversely proportional to the diffusion constant D
      as L(2)/D .

PMID- 17025514
TI  - Effects of substrate network topologies on competition dynamics.
AB  - We study a competition dynamics, based on the minority game, endowed with various
      substrate network structures. We observe the effects of the network topologies by
      investigating the volatility of the system and the structure of follower
      networks. The topology of substrate structures significantly influences the
      system efficiency represented by the volatility and such substrate networks are
      shown to amplify the herding effect and cause inefficiency in most cases. The
      follower networks emerging from the leadership structure show a power-law
      incoming degree distribution. This study shows the emergence of scale-free
      structures of leadership in the minority game and the effects of the interaction
      among players on the networked version of the game.

PMID- 17025515
TI  - Ergodic-nonergodic transition in a threshold system with feedback.
AB  - A threshold system with feedback is studied from the viewpoint of an ergodic
      nonergodic transition, a kind of nonequilibrium phase transition, as the rate of
      input signal variation is changed. By discussing the time evolution of the
      distribution function, instead of its lowest moment (an order parameter), we can
      determine the transition point and make clear the role and limitation of the self
      consistent equation for the order parameter. Finally the feedback strength is
      related to an activation energy from a statistical mechanical viewpoint.

PMID- 17025516
TI  - Dynamics of helping behavior and networks in a small world.
AB  - To investigate an effect of social interaction on the bystanders' intervention in
      emergency situations a rescue model was introduced which includes the effects of
      the victim's acquaintance with bystanders and those among bystanders from a
      network perspective. This model reproduces the experimental result that the
      helping rate (success rate in our model) tends to decrease although the number of
      bystanders k increases. And the interaction among homogeneous bystanders results
      in the emergence of hubs in a helping network. For more realistic consideration
      it is assumed that the agents are located on a one-dimensional lattice (ring),
      then the randomness pE[0,1] is introduced: the kp random bystanders are randomly
      chosen from a whole population and the k-kp near bystanders are chosen in the
      nearest order to the victim. We find that there appears another peak of the
      network density in the vicinity of k=9 and p=0.3 due to the cooperative and
      competitive interaction between the near and random bystanders.

PMID- 17025517
TI  - Networks with given two-point correlations: hidden correlations from degree
      correlations.
AB  - This paper orders certain important issues related to both uncorrelated and
      correlated networks with hidden variables, in which hidden variables correspond
      to desired node degrees. In particular, we show that networks being uncorrelated
      at the hidden level are also lacking in correlations between node degrees. The
      observation supported by the depoissonization idea allows us to extract a
      distribution of hidden variables from a given node degree distribution. It
      completes the algorithm for generating uncorrelated networks that was suggested
      by other authors. In this paper we also carefully analyze the interplay between
      hidden attributes and node degrees. We show how to extract hidden correlations
      from degree correlations. Our derivations provide a mathematical background for
      the algorithm for generating correlated networks that was proposed by Boguna and
      Pastor-Satorras.

PMID- 17025518
TI  - Mixing properties of growing networks and Simpson's paradox.
AB  - The mixing properties of networks are usually inferred by comparing the degree of
      a node with the average degree of its neighbors. This kind of analysis often
      leads to incorrect conclusions: Assortative patterns may appear reversed by a
      mechanism known as Simpson's paradox. We prove this fact by analytical
      calculations and simulations on three classes of growing networks based on
      preferential attachment and fitness, where the disassortative behavior observed
      is a spurious effect. Our results give a crucial contribution to the debate about
      the origin of disassortative mixing, since networks previously classified as
      disassortative reveal instead assortative behavior to a careful analysis.

PMID- 17025519
TI  - Control of unstable steady states by long delay feedback.
AB  - We present an asymptotic analysis of time-delayed feedback control of steady
      states for large delay time. By scaling arguments, and a detailed comparison with
      exact solutions, we establish the parameter ranges for successful stabilization
      of an unstable fixed point of focus type. Insight into the control mechanism is
      gained by analyzing the eigenvalue spectrum, which consists of a pseudocontinuous
      spectrum and up to two strongly unstable eigenvalues. Although the standard
      control scheme generally fails for large delay, we find that if the uncontrolled
      system is sufficiently close to its instability threshold, control does work even
      for relatively large delay times.

PMID- 17025520
TI  - Reconstructing state spaces from multivariate data using variable delays.
AB  - We study two methods for constructing a nonuniform embedding for multivariate
      data. A nonuniform embedding is a state space reconstruction which is more
      flexible than the common delay coordinates with fixed delays since it contains
      variable delays. Using these methods, we can extract causal relationships among
      many variables in a more suitable way. We demonstrate that the proposed methods
      can give more precise predictions and simpler models than some previous methods.

PMID- 17025521
TI  - Reentrant synchronization and pattern formation in pacemaker-entrained Kuramoto
      oscillators.
AB  - We study phase entrainment of Kuramoto oscillators under different conditions on
      the interaction range and the natural frequencies. In the first part the
      oscillators are entrained by a pacemaker acting like an impurity or a defect. We
      analytically derive the entrainment frequency for arbitrary interaction range and
      the entrainment threshold for all-to-all couplings. For intermediate couplings
      our numerical results show a reentrance of the synchronization transition as a
      function of the coupling range. The origin of this reentrance can be traced back
      to the normalization of the coupling strength. In the second part we consider a
      system of oscillators with an initial gradient in their natural frequencies,
      extended over a one-dimensional chain or a two-dimensional lattice. Here it is
      the oscillator with the highest natural frequency that becomes the pacemaker of
      the ensemble, sending out circular waves in oscillator-phase space. No asymmetric
      coupling between the oscillators is needed for this dynamical induction of the
      pacemaker property nor need it be distinguished by a gap in the natural
      frequency.

PMID- 17025522
TI  - Irregular parameter dependence of generalized diffusion coefficients based on
      large deviation statistical analysis.
AB  - The nonperturbative non-Gaussian characteristics of diffusive motion are examined
      in the framework of the large deviation statistical theory, where simple extended
      mapping models showing chaotic diffusion are taken as an example. Furthermore, by
      rigorously solving the large deviation statistical quantities, it is found that
      the same type of anomalous, complex control parameter dependence as that for the
      diffusion coefficient reported by Klages and Dorfman is also observed in the
      large deviation statistical quantities such as the weighted average, the
      generalized diffusion coefficient, and the generalized power spectrum densities.

PMID- 17025523
TI  - Testing for nonlinearity in irregular fluctuations with long-term trends.
AB  - We describe a method for investigating nonlinearity in irregular fluctuations
      (short-term variability) of time series even if the data exhibit long-term trends
      (periodicities). Such situations are theoretically incompatible with the
      assumption of previously proposed methods. The null hypothesis addressed by our
      algorithm is that irregular fluctuations are generated by a stationary linear
      system. The method is demonstrated for numerical data generated by known systems
      and applied to several actual time series.

PMID- 17025524
TI  - Desensitization effects in the ruthenium-catalyzed Belousov-Zhabotinsky reaction.
AB  - The influence of visible light on the velocities of spiral waves in the
      [Ru(bpy)](3)(2+) -catalyzed Belousov-Zhabotinsky (BZ) reaction is well
      documented. However, there are only few reports showing the effect of the way a
      change in the applied intensity is made, or on "desensitization" or "memory" type
      phenomena. In this paper, we present observations showing significant changes in
      spiral tip dynamics without varying the light intensity during the course of the
      experiments. We produce further evidence showing that changes in wave velocity
      and inhibitory effects are depending on whether the increase in intensity is
      applied in one large step or in a number of smaller steps. Also, the tip
      trajectories before and after the spiral waves have been subjected to an increase
      and subsequent decrease in intensity levels are different, suggesting a change in
      excitation of the system. The experimental results are separated into two groups
      depending on the light sensitivity of the system and the behavior of the spiral
      tip. Simulation results demonstrate that the different tip trajectories observed
      in the experiments can be modeled by only varying the excitation threshold. Our
      observations indicate that there must be at least two different competing
      pathways for the reaction mechanism not only in the oscillatory BZ system but
      also in excitable media and that intermediates may also play an important part in
      determining the excitation of the system and not just the initial concentrations
      of the reactants.

PMID- 17025525
TI  - Decay of the Loschmidt echo in a time-dependent environment.
AB  - We study the decay rate of the Loschmidt echo or fidelity in a chaotic system
      under a time-dependent perturbation V(q,t) with typical strength Planck's/tau(v)
      . The perturbation represents the action of an uncontrolled environment
      interacting with the system, and is characterized by a correlation length xi(0)
      and a correlation time tau(0). For small perturbation strengths or rapid
      fluctuating perturbations, the Loschmidt echo decays exponentially with a rate
      predicted by the Fermi "golden rule," 1/approximately tau =tau(c)/tau(v)(2),
      where tau(c) approximately min[tau(0), xi(0)/upsilon] and upsilon is the typical
      particle velocity. Whenever the rate 1/approximately tau is larger than the
      Lyapunov exponent of the system, a perturbation independent Lyapunov decay regime
      arises. We also find that by speeding up the fluctuations (while keeping the
      perturbation strength fixed) the fidelity decay becomes slower, and hence one can
      protect the system against decoherence.

PMID- 17025526
TI  - Suppression of quantum chaos in a quantum computer hardware.
AB  - We present numerical and analytical studies of a quantum computer proposed by the
      Yamamoto group in Phys. Rev. Lett. 89, 017901 (2002). The stable and quantum
      chaos regimes in the quantum computer hardware are identified as a function of
      magnetic field gradient and dipole-dipole couplings between qubits on a square
      lattice. It is shown that a strong magnetic field gradient leads to suppression
      of quantum chaos.

PMID- 17025527
TI  - Energy-second-moment map analysis as an approach to quantify the irregularity of
      Hamiltonian systems.
AB  - A different approach will be presented that aims to scrutinize the phase-space
      trajectories of a general class of Hamiltonian systems with regard to their
      regular or irregular behavior. The approach is based on the "energy-second-moment
      map" that can be constructed for all Hamiltonian systems of the generic form
      H=p(2)/2+V(q,t) . With a three-component vector s consisting of the system's
      energy h and second moments qp, q(2), this map linearly relates the vector s(t)
      at time t with the vector's initial state s(0) at t=0 . It will turn out that
      this map is directly obtained from the solution of a linear third-order equation
      that establishes an extension of the set of canonical equations. The Lyapunov
      functions of the energy-second-moment map will be shown to have simple analytical
      representations in terms of the solutions of this linear third-order equation.
      Applying Lyapunov's regularity analysis for linear systems, we will show that the
      Lyapunov functions of the energy-second-moment map yields information on the
      irregularity of the particular phase-space trajectory. Our results will be
      illustrated by means of numerical examples.

PMID- 17025528
TI  - Classical momentum diffusion in double-delta-kicked particles.
AB  - We investigate the classical chaotic diffusion of atoms subjected to pairs of
      closely spaced pulses ("kicks") from standing waves of light (the 2delta-KP ).
      Recent experimental studies with cold atoms implied an underlying classical
      diffusion of a type very different from the well-known paradigm of Hamiltonian
      chaos, the standard map. The kicks in each pair are separated by a small time
      interval E<<1, which together with the kick strength K, characterizes the
      transport. Phase space for the 2delta-KP is partitioned into momentum "cells"
      partially separated by momentum-trapping regions where diffusion is slow. We
      present here an analytical derivation of the classical diffusion for a 2delta-KP
      including all important correlations which were used to analyze the experimental
      data. We find an asymptotic (t-->infinity) regime of "hindered" diffusion: while
      for the standard map the diffusion rate, for K>>1 , D approximately K(2)/2[1
      2J(2)(K)...] oscillates about the uncorrelated rate D(0)=K(2)/2, we find
      analytically, that the 2delta-KP can equal, but never diffuses faster than, a
      random walk rate. We argue this is due to the destruction of the important
      classical "accelerator modes" of the standard map. We analyze the experimental
      regime 0.1 less or approximately KE less or approximately 1 , where quantum
      localization lengths L approximately Planck's (-0.75) are affected by fractal
      cell boundaries. We find an approximate asymptotic diffusion rate D proportional
      to K(3)E, in correspondence to a D proportional to K(3) regime in the standard
      map associated with the "golden-ratio" cantori.

PMID- 17025529
TI  - Influence of classical resonances on chaotic tunneling.
AB  - Dynamical tunneling between symmetry-related stable modes is studied in the
      periodically driven pendulum. We present strong evidence that the tunneling
      process is governed by nonlinear resonances that manifest within the regular
      phase-space islands on which the stable modes are localized. By means of a
      quantitative numerical study of the corresponding Floquet problem, we identify
      the trace of such resonances not only in the level splittings between near
      degenerate quantum states, where they lead to prominent plateau structures, but
      also in overlap matrix elements of the Floquet eigenstates, which reveal
      characteristic sequences of avoided crossings in the Floquet spectrum. The
      semiclassical theory of resonance-assisted tunneling yields good overall
      agreement with the quantum-tunneling rates, and indicates that partial barriers
      within the chaos might play a prominent role.

PMID- 17025530
TI  - Separation and synchronization of piecewise linear chaotic systems.
AB  - In this paper a topic regarding the synchronization of chaotic systems is dealt
      with: the case of separation and synchronization of many chaotic signals
      generated by different chaotic circuits and combined together is examined. In
      particular, an observer based strategy has been adopted, and an approach for the
      simultaneous stabilization of many Luenberger observers has been investigated to
      face the problem of separation and synchronization. The design strategy is based
      on linear matrix inequalities (LMIs). Indeed, the LMI problem is referred to have
      a solution if a dual optimization problem admits a solution. In our case the
      feasibility condition, if it does exist, allows us to establish that the
      separation and synchronization problem for the chosen circuit admits a solution.
      Some numerical simulations are reported. Further results refer to an experimental
      circuit showing the suitability of the approach. Furthermore, the use of the
      proposed scheme to transmit two or more information masked into two or more
      multiplexed chaotic signals and the design of suitable parameters through the
      introduced technique based on LMIs are discussed.

PMID- 17025531
TI  - Universal finite-sample effect on the perturbation growth in chaotic dynamical
      systems.
AB  - The finite-sample effect on the growth of moments of the perturbation observed in
      numerical simulations of chaotic dynamical systems is studied. To numerically
      estimate the moments, only a limited number of sample trajectories can be
      utilized, and therefore the moments exhibit pure exponential growth only
      initially, and give way to relaxed growth thereafter. Such transition is a
      consequence of the unobservability of rare events in finite sample sets. Using
      the large-deviation formalism for chaotic time series, we estimate the relaxation
      time and derive the post-relaxation growth law. We demonstrate that even after
      the relaxation, each moment still obeys a universal growth law of different type,
      which reflects physical information on the statistics of chaotic expansion rates.

PMID- 17025532
TI  - Dynamics of wrinkle growth and coarsening in stressed thin films.
AB  - A stressed thin film on a soft substrate can develop complex wrinkle patterns.
      The onset of wrinkling and initial growth is well described by a linear
      perturbation analysis, and the equilibrium wrinkles can be analyzed using an
      energy approach. In between, the wrinkle pattern undergoes a coarsening process
      with a peculiar dynamics. By using a proper scaling and two-dimensional numerical
      simulations, this paper develops a quantitative understanding of the wrinkling
      dynamics from initial growth through coarsening till equilibrium. It is found
      that, during the initial growth, a stress-dependent wavelength is selected and
      the wrinkle amplitude grows exponentially over time. During coarsening, both the
      wrinkle wavelength and amplitude increases, following a power-law scaling under
      uniaxial compression. More complicated dynamics is predicted under equibiaxial
      stresses, which starts with a faster coarsening rate before asymptotically
      approaching the same scaling under uniaxial stresses. At equilibrium, a parallel
      stripe pattern is obtained under uniaxial stresses and a chaotic labyrinth
      pattern under equibiaxial stresses. Under stresses of the same magnitude, the two
      patterns have the same average wavelength, but different amplitudes. It is noted
      that the dynamics of wrinkling, while analogous to other phase ordering
      phenomena, is distinct and rich under the effects of stress and substrate
      elasticity.

PMID- 17025533
TI  - Turbulent drag reduction by flexible and rodlike polymers: Crossover effects at
      small concentrations.
AB  - Drag reduction by polymers is bounded between two universal asymptotes, the von
      Karman log law of the law and the maximum drag reduction (MDR) asymptote. It is
      theoretically understood why the MDR asymptote is universal, independent of
      whether the polymers are flexible or rodlike. The crossover behavior from the
      Newtonian von Karman log law to the MDR is, however, not universal, showing
      different characteristics for flexible and rodlike polymers. In this paper we
      provide a theory for this crossover phenomenology.

PMID- 17025534
TI  - Nearly incompressible fluids: hydrodynamics and large scale inhomogeneity.
AB  - A system of hydrodynamic equations in the presence of large-scale inhomogeneities
      for a high plasma beta solar wind is derived. The theory is derived under the
      assumption of low turbulent Mach number and is developed for the flows where the
      usual incompressible description is not satisfactory and a full compressible
      treatment is too complex for any analytical studies. When the effects of
      compressibility are incorporated only weakly, a new description, referred to as
      "nearly incompressible hydrodynamics," is obtained. The nearly incompressible
      theory, was originally applied to homogeneous flows. However, large-scale
      gradients in density, pressure, temperature, etc., are typical in the solar wind
      and it was unclear how inhomogeneities would affect the usual incompressible and
      nearly incompressible descriptions. In the homogeneous case, the lowest order
      expansion of the fully compressible equations leads to the usual incompressible
      equations, followed at higher orders by the nearly incompressible equations, as
      introduced by Zank and Matthaeus. With this work we show that the inclusion of
      large-scale inhomogeneities (in this case time-independent and radially symmetric
      background solar wind) modifies the leading-order incompressible description of
      solar wind flow. We find, for example, that the divergence of velocity
      fluctuations is nonsolenoidal and that density fluctuations can be described to
      leading order as a passive scalar. Locally (for small lengthscales), this system
      of equations converges to the usual incompressible equations and we therefore use
      the term "locally incompressible" to describe the equations. This term should be
      distinguished from the term "nearly incompressible," which is reserved for higher
      order corrections. Furthermore, we find that density fluctuations scale with Mach
      number linearly, in contrast to the original homogeneous nearly incompressible
      theory, in which density fluctuations scale with the square of Mach number.
      Inhomogeneous nearly incompressible equations for higher order fluctuation
      components are derived and it is shown that they converge to the usual
      homogeneous nearly incompressible equations in the limit of no large-scale
      background. We use a time and length scale separation procedure to obtain wave
      equations for the acoustic pressure and velocity perturbations propagating on
      fast-time-short-wavelength scales. On these scales, the pseudosound relation,
      used to relate density and pressure fluctuations, is also obtained. In both
      cases, the speed of propagation (sound speed) depends on background variables and
      therefore varies spatially. For slow-time scales, a simple pseudosound relation
      cannot be obtained and density and pressure fluctuations are implicitly related
      through a relation which can be solved only numerically. Subject to some
      simplifications, a generalized inhomogeneous pseudosound relation is derived.
      With this paper, we extend the theory of nearly incompressible hydrodynamics to
      flows, including the solar wind, which include large-scale inhomogeneities (in
      this case radially symmetric and in equilibrium).

PMID- 17025535
TI  - Stability of liquid metal drops affected by a high-frequency magnetic field.
AB  - The dynamic behavior of liquid metal drops submitted to a high-frequency magnetic
      field is investigated experimentally. The motivation for this study comes from
      the coating industry. In this industry, liquid metals showing a free surface held
      in a dome-type shape are evaporated by applying electromagnetic pressure. The
      Galinstan drops are placed on a curved glass plate. A ringlike inductor fed by an
      alternating electrical current generates the magnetic field. The surface contour
      of the drop is observed using a high-speed camera system. The data are analyzed
      by utilizing image processing methods. In the experiment, we vary the inductor
      current I and the drop volume V while the frequency is fixed at 20 kHz . Upon
      increasing the inductor current within the range 0<I<I(C), we first observe a
      static axisymmetric squeezing. However, when the inductor current exceeds a
      certain critical value, i.e., I>I(C), these symmetric states become unstable to
      capillary waves. The critical current (critical electromagnetic Bond number) as
      well as the critical mode number, the critical frequency, and the amplitudes of
      the waves depend strongly on the volume (Bond number).

PMID- 17025536
TI  - Mechanism of single-bubble sonoluminescence.
AB  - Considering almost all the effective processes of physics and chemical reaction
      in our numerical computation model, we investigate the mechanism of single bubble
      sonoluminescence (SBSL). For those sonoluminescing single bubbles in water at its
      flashing phase, the numerical simulation reveals that if the temperature inside
      the bubble is not high enough which may result in the plenty oxygen molecules and
      OH radicals undissociated, such as the case of a single argon bubble in 20
      degrees C or 34 degrees C water, the radiative attachment of electrons to oxygen
      molecules and OH radicals contributes most to the SBSL; if the temperature inside
      the bubble is higher which makes most of the water vapor inside the bubble
      dissociate into oxygen and hydrogen atoms, such as the case of an argon bubble or
      a helium bubble in 0 degrees C water, the radiative attachment of electrons to
      oxygen and hydrogen atoms dominates the SBSL; if the temperature is still higher,
      such as the case of a xenon bubble in 0 degrees C water, the contribution from
      electron-neutral atom bremsstrahlung and electron-ion bremsstrahlung and
      recombination would be comparable with the contribution from the radiative
      attachment of electrons to oxygen and hydrogen atoms, and they together dominate
      the SBSL. For sonoluminescing single bubbles in those low vapor pressure liquids,
      such as in 85 wt.% sulphuric acid, the electron-neutral atom bremsstrahlung and
      the electron-ion bremsstrahlung and recombination contribute most to the
      continuous spectrum part of SBSL. The present calculation also provides good
      interpretations to those observed phenomena, such as emitted photon numbers, the
      width of optical pulses, the blackbody radiation like spectra. The temperature
      fitted by the blackbody radiation formula is very different from that calculated
      by the gas dynamics equations. Besides, the effect of chemical dissociation on
      the shock wave is also discussed.

PMID- 17025537
TI  - Propagating wave pattern on a falling liquid curtain.
AB  - A regular pattern of surface waves is observed on a liquid curtain falling from a
      horizontal, wetted tube, maintained between two vertical wires. Since the upper
      boundary is not constrained in the transverse direction, the top of the curtain
      enters a pendulum-like motion, when the flow rate is progressively reduced,
      coupled to the propagation of curtain undulations, structured as a checkerboard.
      This structure is formed by two patterns of propagating waves. In some sense,
      these propagating patterns replace the stationary pattern of liquid columns
      observed at a lower flow rate. Measurements of phase velocity, frequency, and
      wavelength are reported. The data are in agreement with a simple dimensional
      argument suggesting that the wave velocity is proportional to the surface tension
      divided by the mass flux of liquid per unit length. This scaling is also that
      followed by the fluid velocity at the so-called transonic point, i.e., the point
      where the fluid velocity equals that of sinuous waves. We finally discuss the
      implications of these results for the global stability of liquid curtains.

PMID- 17025538
TI  - Model for intermittency of energy dissipation in turbulent flows.
AB  - Modeling the intermittent behavior of turbulent energy dissipation processes in
      both space and time is often a relevant problem when dealing with phenomena
      occurring in high-Reynolds-number flows, especially in astrophysical and space
      fluids. In this paper, a dynamical model is proposed to describe the
      intermittency of the energy dissipation rate in a turbulent system. This is done
      by using a shell model to simulate the time evolution of the turbulent cascade
      and introducing some heuristic rules, partly inspired by the well-known p model,
      to construct a spatial structure of the energy dissipation rate. In order to
      validate the model and to study its spatial intermittency properties, a series of
      numerical simulations have been performed. These show that the level of spatial
      intermittency of the system can be simply tuned by varying a single parameter of
      the model and that scaling laws in agreement with those obtained from experiments
      on fully turbulent hydrodynamic flows can be recovered. It is finally suggested
      that the model could represent a useful tool to simulate the intermittent
      structure of turbulent energy dissipation in those high-Reynolds-number
      astrophysical fluids where impulsive energy release processes can be associated
      with the dynamics of the turbulent cascade.

PMID- 17025539
TI  - Vorticity banding in rodlike virus suspensions.
AB  - Vorticity banding under steady shear flow is observed in a suspension of
      semiflexible colloidal rods (fd virus particles) within a part of the paranematic
      nematic biphasic region. Banding occurs uniformly throughout the cell gap within
      a shear-rate interval (.gamma-, .gamma+) , which depends on the fd concentration.
      For shear rates below the lower-border shear rate .gamma- only shear elongation
      of inhomogeneities, which are formed due to paranematic-nematic phase separation,
      is observed. Within a small region just above the upper-border shear rate .gamma+
      , banding occurs heterogeneously. An essential difference in the kinetics of
      vorticity banding is observed, depending on the morphology of inhomogeneities
      formed during the initial stages of the paranematic-nematic phase separation.
      Particle tracking and polarization experiments indicate that the vorticity bands
      are in a weak rolling flow, superimposed on the applied shear flow. We propose a
      mechanism for the origin of the banding instability and the transient stability
      of the banded states. This mechanism is related to the normal stresses generated
      by inhomogeneities formed due to the underlying paranematic-nematic phase
      transition.

PMID- 17025540
TI  - Development of optimal models of porous media by combining static and dynamic
      data: the porosity distribution.
AB  - This paper is part of a project, the goal of which is the development of the
      optimal spatial distributions of the porosity and permeability of a large-scale
      porous medium by using complementary static and dynamic data for the medium. The
      data include limited measurements of the porosity, which the method honors
      (preserves) in the optimal model and utilizes its correlation function, together
      with the first-arrival (FA) times, at a certain number of receivers, of seismic
      waves that have propagated in the medium and the time dependence of the pressure
      of a fluid flowing in the medium. The method uses the simulated-annealing (SA)
      technique in order to develop the optimal model. In the present paper we utilize
      the porosity and FA times data in order to develop the optimal spatial
      distribution of the porosity. This is accomplished by combining the SA method
      with a simulator that solves for the numerical solution of the acoustic-wave
      equation from which the FA times are estimated, limited porosity, and FA times
      data. We show that the optimal model not only honors the data, but also provides
      accurate estimates of the porosities in the rest of the porous medium. The
      efficiency of the computations is discussed in detail.

PMID- 17025541
TI  - Depolarization of decaying counterflow turbulence in He II.
AB  - We present experimental evidence backed up by numerical simulations that the
      steady-state vortex tangle created in He II by heat-transfer counterflow is
      strongly polarized. When the heater that generates the counterflow turbulence is
      switched off, the vortex tangle decays, the vortex lines randomize their spatial
      orientation and the tangle's polarization decreases. The process of
      depolarization slows down the recovery of the transverse second sound signal
      which measures the vortex line density; at some values of parameters it even
      leads to a net decrease of the amplitude of the transverse second sound prior to
      reaching the universal -32 power temporal law decay typical of classical
      homogeneous isotropic turbulence in a finite-sized channel.

PMID- 17025542
TI  - Subgrid-scale modeling of helicity and energy dissipation in helical turbulence.
AB  - The subgrid-scale (SGS) modeling of helical, isotropic turbulence in large eddy
      simulation is investigated by quantifying rates of helicity and energy cascade.
      Assuming Kolmogorov spectra, the Smagorinsky model with its traditional
      coefficient is shown to underestimate the helicity dissipation rate by about 40%.
      Several two-term helical models are proposed with the model coefficients
      calculated from simultaneous energy and helicity dissipation balance. The helical
      models are also extended to include dynamic determination of their coefficients.
      The models are tested a priori in isotropic steady helical turbulence. Together
      with the dynamic Smagorinsky model and the dynamic mixed model, they are also
      tested a posteriori in both decaying and steady isotropic helical turbulence by
      comparing results to direct numerical simulations (DNS). The a priori tests
      confirm that the Smagorinsky model underestimates SGS helicity dissipation,
      although quantitative differences with the predictions are observed due to the
      finite Reynolds number of the DNS. Also, in a posteriori tests improvement can be
      achieved for the helicity decay rate with the proposed models, compared with the
      Smagorinsky model. Overall, however, the effect of the new helical terms added to
      obtain the correct rate of global helicity dissipation is found to be quite
      small. Within the small differences, the various versions of the dynamic model
      provide the results closest to the DNS. The dynamic model's good performance in
      capturing mean kinetic energy dissipation at the finite Reynolds number of the
      simulations appears to be the most important aspect in accounting also for
      accurate prediction of the helicity dissipation.

PMID- 17025543
TI  - Monte Carlo simulation of liquid bridge rupture: application to lung physiology.
AB  - In the course of certain lung diseases, the surface properties and the amount of
      fluids coating the airways changes and liquid bridges may form in the small
      airways blocking the flow of air, impairing gas exchange. During inhalation,
      these liquid bridges may rupture due to mechanical instability and emit a
      discrete sound event called pulmonary crackle, which can be heard using a simple
      stethoscope. We hypothesize that this sound is a result of the acoustical release
      of energy that had been stored in the surface of liquid bridges prior to its
      rupture. We develop a lattice gas model capable of describing these phenomena. As
      a step toward modeling this process, we address a simpler but related problem,
      that of a liquid bridge between two planar surfaces. This problem has been
      analytically solved and we use this solution as a validation of the lattice gas
      model of the liquid bridge rupture. Specifically, we determine the surface free
      energy and critical stability conditions in a system containing a liquid bridge
      of volume Omega formed between two parallel planes, separated by a distance 2h,
      with a contact angle Theta using both Monte Carlo simulation of a lattice gas
      model and variational calculus based on minimization of the surface area with the
      volume and the contact angle constraints. In order to simulate systems with
      different contact angles, we vary the parameters between the constitutive
      elements of the lattice gas. We numerically and analytically determine the phase
      diagram of the system as a function of the dimensionless parameters hOmega(-1/3)
      and Theta. The regions of this phase diagram correspond to the mechanical
      stability and thermodynamical stability of the liquid bridge. We also determine
      the conditions for the symmetrical versus asymmetrical rupture of the bridge. We
      numerically and analytically compute the release of free energy during rupture.
      The simulation results are in agreement with the analytical solution.
      Furthermore, we discuss the results in connection to the rupture of similar
      bridges that exist in diseased lungs.

PMID- 17025544
TI  - Energetic proton acceleration and bunch generation by ultraintense laser pulses
      on the surface of thin plasma targets.
AB  - Energetic proton acceleration from concave targets, the front of which were
      irradiated with 40 fs laser pulses with an intensity of 10(20)W/cm(2), has been
      studied as a function of the depth of the concave shape. Three kinds of targets,
      a triangular concave target, a circular concave target and a parabolic concave
      target are considered. When the depth of the concave shape was varied, the peak
      proton energy showed a maximum. The underlying mechanism for the existence of a
      maximum peak proton energy is presented by tracing the proton trajectory. It is
      concluded that a parabolic concave target is the best, among the targets
      considered, for accelerating a proton beam, since a proton beam from a parabolic
      concave target goes through the strongest electric field.

PMID- 17025545
TI  - Generalized x-ray scattering cross section from nonequilibrium plasmas.
AB  - We propose a modified x-ray form factor that describes the scattering cross
      section in warm dense matter valid for both the plasma and the solid
      (crystalline) state. Our model accounts for the effect of lattice correlations on
      the electron-electron dynamic structure, as well as provides a smooth transition
      between the solid and the plasma scattering cross sections. In addition, we
      generalize the expression of the dynamic structure in the case of a two
      temperature system (with different electron and ion temperatures). This work
      provides a unified description of the x-ray scattering processes in warm and
      dense matter, as the one encountered in inertial confinement fusion, laboratory
      astrophysics, material science, and high-energy density physics and it can be
      used to verify temperature relaxation mechanisms in such environments.

PMID- 17025546
TI  - Residual dust charges in discharge afterglow.
AB  - An on-ground measurement of dust-particle residual charges in the afterglow of a
      dusty plasma was performed in a rf discharge. An upward thermophoretic force was
      used to balance the gravitational force. It was found that positively charged,
      negatively charged, and neutral dust particles coexisted for more than 1 min
      after the discharge was switched off. The mean residual charge for 200-nm-radius
      particles was measured. The dust particle mean charge is about -5e at a pressure
      of 1.2 mbar and about -3e at a pressure of 0.4 mbar .

PMID- 17025547
TI  - Experimental investigations of plasma perturbation in Thomson scattering applied
      to thermal plasma diagnostics.
AB  - Time and space resolved measurements of Thomson scattering of 532 nm , 6 ns laser
      pulses were performed on argon thermal discharge plasma with electron temperature
      T(e)>10,000 K and electron density 8 x 10(22) m(-3)< n(e)<2 x 10(23) m(-3). From
      these measurements, variations of the electron density and temperature across the
      laser beam and their evolution during the laser pulse were determined. While the
      electron density is augmented by no more than a few percent the electron
      temperature is significantly increased along the axis of the laser beam due to
      laser heating. It is also shown that the higher initial electron density, the
      more disturbed is the plasma. The initial "undisturbed" electron density was
      derived by studying the spatial variations of n(e) within the laser beam. On the
      other hand, the initial electron temperature was determined by studying the
      temporal evolution of T(e) during the laser pulse and then by extrapolating the
      results to the origin of the pulse. Despite strong and nonlinear plasma heating
      by the Thomson scattered laser light, our study yields temperatures close to
      those obtained by modeling and time-resolved spectroscopic measurements.

PMID- 17025548
TI  - Magnetic field effects on spatial relaxation of swarm particles in the idealized
      steady-state Townsend experiment.
AB  - The effect of a magnetic field at right angles to an electric field on spatial
      relaxation of a swarm of charged particles emitted by a plane source into a gas
      the idealized steady-state Townsend experiment-is examined. The Boltzmann
      equation is solved using an adaptation of the "two-temperature" moment method,
      involving a Burnett function representation of the velocity distribution
      function, a technique which is valid for charged particles of arbitrary mass and
      is intrinsically of a "multiterm" nature. Results are presented for electrons in
      model and real gases, and are benchmarked against an exact analytical solution of
      the Boltzmann equation for a particular collision model. The application of a
      magnetic field significantly alters the relaxation profiles: in general, it can
      both enhance or retard spatial relaxation of transport properties. For methane
      gas, a multiterm analysis is essential to correctly account for the relaxation
      near the source, even though a two-term approximation may be sufficient when the
      magnetic field is sufficiently strong and hydrodynamic conditions dominate.

PMID- 17025549
TI  - Secondary electron emission of carbonaceous dust particles.
AB  - In this paper we present measurements of the secondary electron emission yield
      (gamma) of a carbonaceous dust particle material, which was grown in argon
      diluted acetylene plasmas. One aim was to reach a better understanding of
      charging and discharging processes of dust particles in complex plasmas due to
      secondary electron emission and consequently to try to explain the anomalous
      behavior of electron density observed in afterglows of pulsed rf plasmas. We
      compared the results of a simple model and of a Monte Carlo simulation to the
      previously measured time dependence of the electron density in complex plasma
      afterglow. It was found that the value of the intrinsic secondary electron yield
      from the carbonaceous dust material is too low to explain the increase of
      electron density in the afterglow. It is, however, possible that the electrons
      charging the particles are weakly attached so that they may be released with high
      efficiency by ion bombardment due to field induced emission or by other
      mechanisms.

PMID- 17025550
TI  - Radiative damping and electron beam dynamics in plasma-based accelerators.
AB  - The effects of radiation reaction on electron beam dynamics are studied in the
      context of plasma-based accelerators. Electrons accelerated in a plasma channel
      undergo transverse betatron oscillations due to strong focusing forces. These
      oscillations lead to emission by the electrons of synchrotron radiation, with a
      corresponding energy loss that affects the beam properties. An analytical model
      for the single particle orbits and beam moments including the classical radiation
      reaction force is derived and compared to the results of a particle transport
      code. Since the betatron amplitude depends on the initial transverse position of
      the electron, the resulting radiation can increase the relative energy spread of
      the beam to significant levels (e.g., several percent). This effect can be
      diminished by matching the beam into the channel, which could require micron
      sized beam radii for typical values of the beam emittance and plasma density.

PMID- 17025551
TI  - Gap solitons in quasiperiodic optical lattices.
AB  - Families of solitons in one- and two-dimensional (1D and 2D) Gross-Pitaevskii
      equations with the repulsive nonlinearity and a potential of the quasicrystallic
      type are constructed (in the 2D case, the potential corresponds to a fivefold
      optical lattice). Stable 1D solitons in the weak potential are explicitly found
      in three band gaps. These solitons are mobile, and they collide elastically. Many
      species of tightly bound 1D solitons are found in the strong potential, both
      stable and unstable (unstable ones transform themselves into asymmetric
      breathers). In the 2D model, families of both fundamental and vortical solitons
      are found and are shown to be stable.

PMID- 17025552
TI  - Tunneling escape in optical waveguide arrays with a boundary defect.
AB  - Tuning of the decay law of light in an array of tunneling-coupled optical
      waveguides with a defect is theoretically demonstrated. An analytical form for
      the decay law in terms of a Neumann series is obtained in case of a semi-infinite
      array with a boundary defect waveguide. Different decay regimes, ranging from a
      near-exponential decay to an oscillatory or nonoscillatory power-law decay, are
      found in the parameter range where the boundary defect waveguide does not support
      localized modes.

PMID- 17025553
TI  - Wide-angle coupling into rod-type photonic crystals with ultralow reflectance.
AB  - We describe the surprising phenomenon of near-perfect coupling from free space
      into uniform two-dimensional rod-type photonic crystals over a wide range of
      incident angles. This behavior is shown to be a generic feature of many rod-type
      photonic crystal structures that is related to strong forward scattering
      resonances of the individual cylinders. We explain these results using both
      semianalytic analysis and two-dimensional numerical calculations and identify the
      conditions under which efficient, wide-angle coupling can occur. The results may
      lead to more efficient designs for in-band photonic crystal devices such as
      superprisms and self-collimation based photonic circuits.

PMID- 17025554
TI  - Microscale multiple scattering of coherent surface acoustic wave packets probed
      with gigahertz time-reversal acoustics.
AB  - The multiple scattering of coherent surface acoustic wave packets in a
      microstructure is studied using an ultrafast optical technique. By recording a
      set of acoustic transfer functions, we show that it is possible to implement time
      reversal acoustics and refocus the wave packets up to the GHz range, two orders
      of magnitude higher than usual. Many applications in time-reversal acoustics are
      thus transposable to correspondingly smaller structures, opening the way to
      efficient nondestructive characterization and manipulation of multiple scattering
      on the microscale.

PMID- 17025555
TI  - Discrete vector solitons in one-dimensional lattices in photorefractive media.
AB  - We construct families of two-component spatial solitons in a one-dimensional
      lattice with saturable on-site nonlinearity (focusing or defocusing) in a
      photorefractive crystal. We identify 14 species of vector solitons, depending on
      their type (bright/dark), phase (in-phase/staggered), and location on the lattice
      (on/off-site). Two species of the bright/bright type form entirely stable soliton
      families, four species are partially stable (depending on the value of the
      propagation constant), while the remaining eight species are completely unstable.
      "Symbiotic" soliton pairs (of the bright/dark type), which contain components
      that cannot exist in isolation in the same model, are found as well.

PMID- 17025556
TI  - Soliton dynamics in deformable nonlinear lattices.
AB  - We describe wave propagation and soliton localization in photonic lattices, which
      are induced in a nonlinear medium by an optical interference pattern, taking into
      account the inherent lattice deformations at the soliton location. We obtain
      exact analytical solutions and identify the key factors defining soliton
      mobility, including the effects of gap merging and lattice imbalance, underlying
      the differences with discrete and gap solitons in conventional photonic
      structures.

PMID- 17025557
TI  - Design for electromagnetic wave transparency with metamaterials.
AB  - With the help of the "neutral inclusion" concept, the conditions of
      electromagnetic wave transparency for multilayered spheres, coated spheroids, and
      general particulate composites are analytically derived in the quasistatic case.
      The basic idea is to make the effective material property of a composite region
      equal to that of the surrounding medium. The general full-wave analysis shows
      that the obtained quasistatic conditions are useful in designing the
      electromagnetically transparent materials.

PMID- 17025558
TI  - Second-harmonic generation at angular incidence in a negative-positive index
      photonic band-gap structure.
AB  - In the spectral region where the refractive index of the negative index material
      is approximately zero, at oblique incidence, the linear transmission of a finite
      structure composed of alternating layers of negative and positive index materials
      manifests the formation of a new type of band gap with exceptionally narrow band
      edge resonances. In particular, for TM-polarized (transverse magnetic) incident
      waves, field values that can be achieved at the band edge may be much higher
      compared to field values achievable in standard photonic band-gap structures. We
      exploit the unique properties of these band-edge resonances for applications to
      nonlinear frequency conversion, second-harmonic generation, in particular. The
      simultaneous availability of high field localization and phase matching
      conditions may be exploited to achieve second-harmonic conversion efficiencies
      far better than those achievable in conventional photonic band-gap structures.
      Moreover, we study the role played by absorption within the negative index
      material, and find that the process remains efficient even for relatively high
      values of the absorption coefficient.

PMID- 17025559
TI  - Dynamic radiation force of acoustic waves on solid elastic spheres.
AB  - The present study concerns the dynamic radiation force on solid elastic spheres
      exerted by a plane wave with two frequencies (bichromatic wave) considering the
      nonlinearity of the fluid. Our approach is based on solving the wave scattering
      for the sphere in the quasilinear approximation within the preshock wave range.
      The dynamic radiation force is then obtained by integrating the component of the
      momentum flux tensor at the difference of the primary frequencies over the
      boundary of the sphere. Results reveal that effects of the nonlinearity of the
      fluid play a major role in dynamic radiation force leading it to a parametric
      amplification regime. The developed theory is used to calculate the dynamic
      radiation force on three different solid spheres (aluminum, silver, and
      tungsten). Resonances are observed in the spectrum of the force on the spheres.
      They have larger amplitude and better shape than resonances present in static
      radiation force.

PMID- 17025560
TI  - Statics and dynamics of Bose-Einstein condensates in double square well
      potentials.
AB  - We treat the behavior of Bose-Einstein condensates in double square well
      potentials of both equal and different depths. For even depth, symmetry
      preserving solutions to the relevant nonlinear Schrodinger equation are known,
      just as in the linear limit. When the nonlinearity is strong enough, symmetry
      breaking solutions also exist, side by side with the symmetric one.
      Interestingly, solutions almost entirely localized in one of the wells are known
      as an extreme case. Here we outline a method for obtaining all these solutions
      for repulsive interactions. The bifurcation point at which, for critical
      nonlinearity, the asymmetric solutions branch off from the symmetry preserving
      ones is found analytically. We also find this bifurcation point and treat the
      solutions generally via a Josephson junction model. When the confining potential
      is in the form of two wells of different depth, interesting phenomena appear.
      This is true of both the occurrence of the bifurcation point for the static
      solutions and also of the dynamics of phase and amplitude varying solutions.
      Again a generalization of the Josephson model proves useful. The stability of
      solutions is treated briefly.

PMID- 17025561
TI  - Variational treatment of the Shastry-Sutherland antiferromagnet using projected
      entangled pair states.
AB  - We have applied a variational algorithm based on projected entangled pair states
      (PEPS) to a two dimensional frustrated spin system, the spin-1/2
      antiferromagnetic Heisenberg model on the Shastry-Sutherland lattice. We use the
      class of PEPS with internal tensor dimension D=2 , the first step beyond product
      states (D=1 PEPS). We have found that the D=2 variational PEPS algorithm is able
      to capture the physics in both the valence-bond crystal and the Neel ordered
      state. Also the spin textures giving rise to the magnetization plateaus seen in
      experiments on SrCu2(BO3)(2) are well reproduced. This shows that PEPS with the
      smallest nontrivial internal dimension, D=2 , can provide valuable insights into
      frustrated spin systems.

PMID- 17025562
TI  - Improving the global fitting method on nonlinear time series analysis.
AB  - We are concerned with improving the forecast capabilities of the global approach
      to time series. We assume that the normal techniques of global mapping are
      applied, the noise reduction is performed, etc. Then, using the mathematical
      foundations behind such approaches, we propose a method that, without a great
      computational cost, greatly increases the accuracy of the corresponding
      forecasting.

PMID- 17025563
TI  - Deterministic walks as an algorithm of pattern recognition.
AB  - New tools for automatically finding data clusters that share statistical
      properties in a heterogeneous data set are imperative in pattern recognition
      research. Here we introduce a deterministic procedure as a tool for pattern
      recognition in a hierarchical way. The algorithm finds attractors of mutually
      close points based on the neighborhood ranking. A memory parameter mu acts as a
      hierarchy parameter, in which the clusters are identified. The final result of
      the method is a general tree that represents the nesting structure of the data in
      an invariant way by scale transformation.

PMID- 17025564
TI  - Transport on adaptive random lattices.
AB  - In this paper, we present a method for the solution of those linear transport
      processes that may be described by a master equation, such as electron, neutron,
      and photon transport, and more exotic variants thereof. We base our algorithm on
      a Markov process on a Voronoi-Delaunay grid, a nonperiodic lattice which is
      derived from a random point process that is chosen to optimally represent certain
      properties of the medium through which the transport occurs. Our grid is locally
      translation and rotation invariant in the mean. We illustrate our approach by
      means of a particular example, in which the expectation value of the length of a
      grid line corresponds to the local mean free path. In this example, the lattice
      is a direct representation of the "free path space" of the medium. Subsequently,
      transport is defined as simply moving particles from one node to the next,
      interactions taking place at each point. We derive the statistical properties of
      such lattices, describe the limiting behavior, and show how interactions are
      incorporated as global coefficients. Two elementary linear transport problems are
      discussed: that of free ballistic transport, and the transport of particles
      through a scattering medium. We also mention a combination of these two. We
      discuss the efficiency of our method, showing that it is much faster than most
      other methods because the operation count does not scale with the number of
      sources. We test our method by focusing on the transport of ionizing radiation
      through a static medium, and show that the computed results for the classical
      test case of an ionization front expanding in a homogeneous medium agree
      perfectly with the analytic solution. We finish by illustrating the efficiency
      and flexibility of our method with the results of a simulation of the
      reionization of the large scale structure of the Universe.

PMID- 17025565
TI  - Galilean invariant lattice Boltzmann scheme for natural convection on square and
      rectangular lattices.
AB  - In this paper we present lattice Boltzmann (LB) schemes for convection diffusion
      coupled to fluid flow on two-dimensional rectangular lattices. Via inverse
      Chapman-Enskog analysis of LB schemes including source terms, we show that for
      consistency with physics it is required that the moments of the equilibrium
      distributions equal those of the Maxwell-Boltzmann distribution. These
      constraints can be satisfied for the rectangular D2Q9 lattice for only fluid flow
      in the weakly compressible regime. The analysis of source terms shows that fluxes
      are really defined on the boundaries of the Wigner-Seitz cells, and not on the
      lattice sites where the densities are defined-which is quite similar to the
      staggered grid finite-volume schemes. Our theoretical findings are confirmed by
      numerical solutions of benchmark problems for convection diffusion and natural
      convection. The lattice Boltzmann scheme shows remarkably good performance for
      convection diffusion, showing little to non-numerical diffusion or numerical
      dispersion, even at high grid Peclet numbers.

PMID- 17025566
TI  - Random walk approximation of fractional-order multiscaling anomalous diffusion.
AB  - Random walks are developed to approximate the solutions of multiscaling,
      fractional-order, anomalous diffusion equations. The essential elements of the
      diffusion are described by the matrix-order scaling indexes and the mixing
      measure, which describes the diffusion coefficient in every direction. Two forms
      of the governing equation (also called the multiscaling fractional diffusion
      equation), based on fractional flux and fractional divergence, are considered,
      where the diffusion coefficient and the drift vary in space. The particle
      tracking algorithm is also extended to approximate anomalous diffusion with a
      streamline-dependent mixing measure, using a streamline-projection technique. In
      this and other general cases, the random walk method is the only known way to
      solve the nonhomogeneous equations. Five numerical examples demonstrate the
      flexibility, simplicity, and efficiency of the random walk method.

PMID- 17025567
TI  - Efficiency of rejection-free dynamic Monte Carlo methods for homogeneous spin
      models, hard disk systems, and hard sphere systems.
AB  - We construct asymptotic arguments for the relative efficiency of rejection-free
      Monte Carlo (MC) methods compared to the standard MC method. We find that the
      efficiency is proportional to exp(constbeta) in the Ising, sqrt[beta] in the
      classical XY, and beta in the classical Heisenberg spin systems with inverse
      temperature beta, regardless of the dimension. The efficiency in hard particle
      systems is also obtained, and found to be proportional to (rho(cp)-rho)(-d) with
      the closest packing density rho(cp), density rho, and dimension d of the systems.
      We construct and implement a rejection-free Monte Carlo method for the hard-disk
      system. The RFMC has a greater computational efficiency at high densities, and
      the density dependence of the efficiency is as predicted by our arguments.

PMID- 17025568
TI  - Impact of noise on domain growth in electroconvection.
AB  - The growth and ordering of striped domains has recently received renewed
      attention due in part to experimental studies in diblock copolymers and
      electroconvection. One surprising result has been the relatively slow dynamics
      associated with the growth of striped domains. One potential source of the slow
      dynamics is the pinning of defects in the periodic potential of the stripes. Of
      interest is whether or not external noise will have a significant impact on the
      domain ordering, perhaps by reducing the pinning and increasing the rate of
      ordering. In contrast, we present experiments using electroconvection in which we
      show that a particular type of external noise decreases the rate of domain
      ordering.

PMID- 17025569
TI  - Comparison of experimental and simulated Kalpha yield for 400 nm ultrashort pulse
      laser irradiation.
AB  - Ti Kalpha emission yields from foils irradiated with approximately 45 fs, p
      polarized pulses of a frequency-doubled Ti:sapphire laser are presented. A simple
      model invoking vacuum heating to predict absorption and hot electron temperature
      was coupled with the cross section for K -shell ionization of Ti and the Bethe
      Bloch stopping power equation for electrons. The peak predicted Kalpha emission
      was in generally good agreement with experiment. This contrasts strongly with
      previous work at the fundamental frequency. Similar predictions using particle-in
      cell (PIC) code simulation to estimate the number and temperature of hot
      electrons also gave good agreement for yield.

PMID- 17025570
TI  - Incoherent accessible white-light solitons in strongly nonlocal Kerr media.
AB  - We present a theoretical investigation of incoherent accessible white-light
      solitons in strongly nonlocal medium with noninstantaneous Kerr nonlinearity.
      This soliton has elliptic Gaussian intensity profile and anisotropic
      spatiotemporal coherence properties. For this soliton to exist, the spatial
      coherence distance should be larger for lower frequencies and shorter for higher
      frequencies. When the incident power differs from the critical value, we
      demonstrate the periodic harmonic oscillations of the accessible white-light
      solitons.

PMID- 17025571
TI  - Painleve classification of a generalized coupled Hirota system.
AB  - By means of singularity analysis, the integrability of a system of generalized
      coupled Hirota equations with parameter coefficients is tested. It is proven that
      the system passes the Painleve test for integrability only in two distinct cases.

PMID- 17025572
TI  - Last-passage Monte Carlo algorithm for mutual capacitance.
AB  - We develop and test the last-passage diffusion algorithm, a charge-based Monte
      Carlo algorithm, for the mutual capacitance of a system of conductors. The first
      passage algorithm is highly efficient because it is charge based and incorporates
      importance sampling; it averages over the properties of Brownian paths that
      initiate outside the conductor and terminate on its surface. However, this
      algorithm does not seem to generalize to mutual capacitance problems. The last
      passage algorithm, in a sense, is the time reversal of the first-passage
      algorithm; it involves averages over particles that initiate on an absorbing
      surface, leave that surface, and diffuse away to infinity. To validate this
      algorithm, we calculate the mutual capacitance matrix of the circular-disk
      parallel-plate capacitor and compare with the known numerical results. Good
      agreement is obtained.

PMID- 17025573
TI  - Optimization of nonlinear parameters in trial wave functions with a very large
      number of terms.
AB  - A procedure is proposed to construct highly accurate variational wave functions
      with large and very large numbers of basis functions. The procedure has a number
      of advantages in actual computations on parallel computer clusters. In
      particular, by using this procedure we have determined very accurate numerical
      values of the ground-state energies in the positronium ion Ps(-) (or e(-)e(+)e(
      )) (E= -0.262 005 070 232 980 107 770 375 a.u.) and hydrogen ion infinityH(-) (E=
      -0.527 751 016 544 377 196 589 759 a.u.) The variational energies of the negative
      hydrogenlike ions (or H(-)-like ions) with the finite nuclear masses (T(-), D(-),
      1H(-), and Mu(-)) are also presented. These energies are the best variational
      ground-state energies ever obtained for these ions.

PMID- 17025574
TI  - Comment on "Connection between the Burgers equation with an elastic forcing term
      and a stochastic process".
AB  - In the above mentioned paper by E. Moreau and O. Vallee [Phys. Rev. E 73, 016112
      (2006)], the one-dimensional Burgers equation with an elastic (attractive)
      forcing term has been claimed to be connected with the Ornstein-Uhlenbeck
      process. We point out that this connection is valid only in the case of repulsive
      forcing.

PMID- 17025576
TI  - Field theories and exact stochastic equations for interacting particle systems.
AB  - We consider the dynamics of interacting particles with reaction and diffusion.
      Starting from the underlying discrete stochastic jump process we derive a general
      field theory describing the dynamics of the density field, which we relate to an
      exact stochastic equation on the density field. We show how our field theory maps
      onto the original Doi-Peliti formalism, allowing us to clarify further the issue
      of the "imaginary" Langevin noise that appears in the context of reaction
      diffusion processes. Our procedure applies to a wide class of problems and is
      related to large deviation functional techniques developed recently to describe
      fluctuations of nonequilibrium systems in the hydrodynamic limit.

PMID- 17025577
TI  - Positional order and diffusion processes in particle systems.
AB  - The relaxation of a nonequilibrium solid to a fluid is determined by observing
      the positional order parameter in Monte Carlo simulations, and discussed based on
      diffusion processes in the hard-particle systems. From the cumulant expansion up
      to the second order, the relation between the positional order parameter Psi and
      the mean square displacement <mui2> is obtained to be Psi approximately exp(
      K2<mui2>/2d) with a reciprocal vector K and the dimension of the system d. On the
      basis of this relation, the positional order should decay exponentially as Psi is
      approximately exp(-K2Dt) when the system involves normal diffusion with a
      diffusion constant D. A diffusion process with swapping positions of particles is
      also discussed. The swapping of particles contributes to the higher orders of the
      cumulants, and swapping positions allows particles to diffuse without destroying
      the positional order while the normal diffusion destroys it.

PMID- 17025578
TI  - Optical microscopy measurement of pair correlation functions.
AB  - We studied the pair correlation function g(r) of silica particles with a
      fluorescent core and a nonfluorescent shell which were confined between two glass
      plates by optical video microscopy. To investigate the possible role of optical
      artifacts due to overlapping particle images, we compared experiments, where,
      first, the whole particle (white image) and then, only the fluorescent core
      (fluorescent image) was used for determining particle positions. While under
      white-image conditions the observed g(r) exhibits a main peak at about 1.2 times
      the particle's diameter; under fluorescent image conditions the obtained g(r)
      resembles a short-ranged repulsive system where the main peak is close to
      contact. This discrepancy points towards artifacts of video microscopy, leading
      to erroneous g(r) and in turn to erroneous effective-pair potentials.

PMID- 17025579
TI  - Counterion release in overcharging of polyion-liposome complexes.
AB  - We present a set of electrical conductivity measurements of a mesoscopic
      equilibrium cluster phase in the aggregation process of charged particles induced
      by oppositely charged polyions. These measurements supply strong experimental
      evidence that correlated adsorption of polyions is driven by the counterion
      release. This phenomenon, known to occur in DNA-liposome mixtures in lamellar
      phase, i.e., when liposomes fuse together to form a sandwichlike structure
      encompassing DNA chains, was not previously observed in aqueous suspension of
      clusters of intact liposomes stuck together by polyions to form reversible
      aggregates. A simple statistical model of the lateral correlation of polyions at
      the particle surface justifies quantitatively the observed behavior of the
      counterion release, as shown by electrical conductivity measurements.

PMID- 17025580
TI  - Orientational ordering of a banana-shaped solute molecule in a nematic calamitic
      solvent by 2H-NMR spectroscopy: an indication of glasslike behavior.
AB  - The Saupe ordering matrix of a banana-shaped mesogenic molecule as a solute in a
      common nematic calamitic solvent has been determined by 2H-NMR spectroscopy as a
      function of temperature. The temperature dependence of the Saupe ordering matrix
      element associated with the principal molecular axis is consistent with a glassy
      behavior in the reorientational motion of this particular solute molecule. The
      Haller expression, appropriately modified, provides a good fit to the
      experimental data.

PMID- 17025581
TI  - Smectic-Calpha*-smectic-C* phase transition and critical point in binary
      mixtures.
AB  - We have investigated the smectic-Calpha*-smectic-C* (SmCalpha*-SmC*) transition
      in a series of binary mixtures with resonant x-ray diffraction, differential
      optical reflectivity, and heat capacity measurements. Results show that the
      phases are separated by a first-order transition that ends at a critical point.
      We report the observation of such a critical point. We have proposed the
      appropriate order parameter and obtained values of two critical exponents
      associated with this transition. The values of the critical exponents suggest
      that long-range interactions are present in the SmCalpha*-SmC* critical region.

PMID- 17025582
TI  - Multiscale modeling of polymer rheology.
AB  - We propose a simulation method which can be used to readily parallelize
      simulations on systems with a large spatial extent. We simulate small parts of
      the system with independent molecular dynamics simulations, and only occasionally
      pass information between them through a constitutive model free continuum
      approach. We illustrate the power of this method in the case of a polymeric fluid
      undergoing rapid one-dimensional shear flow. Since we show that this flow problem
      cannot be modeled by using a steady-state constitutive model, this method offers
      the unique capability for accessing the nonlinear viscoelasticity of complex
      fluids.

PMID- 17025583
TI  - Direct method to study membrane rigidity of small vesicles based on atomic force
      microscope force spectroscopy.
AB  - Mechanical properties of lipidic membranes such as their bending rigidity are
      governing liposome morphology and play an important role in processes like
      membrane fusion and adhesion. Force versus deformation measurements are the most
      direct means to determine this, but so far experimental data is scarce and mainly
      stems from techniques that are limited to giant vesicles. We present atomic force
      microscope force spectroscopy as a method allowing force-deformation measurements
      of submicron vesicles. Bending rigidities of small unilamellar
      dipalmitoylphosphatidylcholine (DPPC) liposomes (R<200 nm) can be derived from
      the force-deformation data using analytical models based on shell theory and are
      in good agreement with independent measurements.

PMID- 17025584
TI  - Single molecule Michaelis-Menten equation beyond quasistatic disorder.
AB  - The classic Michaelis-Menten equation describes the catalytic activities for
      ensembles of enzyme molecules very well. But recent single-molecule experiments
      showed that the waiting time distribution and other properties of single enzyme
      molecules were not consistent with the prediction based on the ensemble
      viewpoint. They have contributed to the slow conformational changes of a single
      enzyme in the catalytic processes. In this work, we study the general dynamics of
      single enzymes in the presence of dynamic disorder. We find that, within the time
      separation regimes, i.e., the slow reaction and nondiffusion limits, the
      Michaelis-Menten equation holds exactly. In particular, by employing the
      decoupling approximation we demonstrate analytically that the classic Michaelis
      Menten equation is still an excellent approximation in the presence of general
      dynamic disorder.

PMID- 17025585
TI  - Stochastic synchronization in finite size spiking networks.
AB  - We study a stochastic synchronization of spiking activity in feedforward networks
      of integrate-and-fire model neurons. A stochastic mean field analysis shows that
      synchronization occurs only when the network size is sufficiently small. This
      gives evidence that the dynamics, and hence processing, of finite size
      populations can be drastically different from that observed in the infinite size
      limit. Our results agree with experimentally observed synchrony in cortical
      networks, and further strengthen the link between synchrony and propagation in
      cortical systems.

PMID- 17025586
TI  - Nonequilibrium clustering of self-propelled rods.
AB  - Motivated by aggregation phenomena in gliding bacteria, we study collective
      motion in a two-dimensional model of active, self-propelled rods interacting
      through volume exclusion. In simulations with individual particles, we find that
      particle clustering is facilitated by a sufficiently large packing fraction eta
      or length-to-width ratio kappa . The transition to clustering in simulations is
      well captured by a mean-field model for the cluster size distribution, which
      predicts that the transition values kappac of the aspect ratio for a fixed
      packing fraction eta are given by kappac=Ceta-1 where C is a constant.

PMID- 17025587
TI  - Nonequilibrium molecular dynamics calculation of the conductance of the KcsA
      potassium ion channel.
AB  - We have developed an efficient method for the atomistic determination of the
      conductance of a biological ion channel model by applying an external field to
      the conducting ions only. The underlying theory is discussed and demonstrated in
      a simple test system consisting of two ions in a box of water. Finally, the
      theory is applied to the experimentally determined structure of the KcsA
      potassium channel from which a conductance in reasonable agreement with the
      experimental result is predicted.

PMID- 17025588
TI  - Irreversible growth of binary mixtures on small-world networks.
AB  - Binary mixtures growing on small-world networks under far-from-equilibrium
      conditions are studied by means of extensive Monte Carlo simulations. For any
      positive value of the shortcut fraction of the network (p>0), the system
      undergoes a continuous order-disorder phase transition, while it is noncritical
      in the regular lattice limit (p=0). Using finite-size scaling relations, the
      phase diagram is obtained in the thermodynamic limit and the critical exponents
      are evaluated. The small-world networks are thus shown to trigger criticality, a
      phenomenon analogous to similar observations reported recently in the
      investigation of equilibrium systems.

PMID- 17025589
TI  - Noise-enhanced Fisher information in parallel arrays of sensors with saturation.
AB  - This paper investigates stochastic resonance in parallel arrays of uncoupled
      saturating devices. The Fisher information is used to demonstrate the possibility
      of noise improved parameter estimation for arbitrary parametric signals.
      Especially, it is shown that improvement by noise always occurs in these arrays,
      for any configuration of the input signal, even in optimal configuration. The
      results contribute to establish stochastic resonance in parallel uncoupled arrays
      as a general mechanism of enhancement by noise, which can occur in wide classes
      of nonlinearities and for various information processing tasks. It can supplement
      other mechanisms of stochastic resonance that take place in isolated
      nonlinearities but generally in restricted configurations of the input signal.

PMID- 17025590
TI  - Analysis and visualization of multiply oriented lattice structures by a two
      dimensional continuous wavelet transform.
AB  - The phase-field-crystal model [K. R. Elder and M. Grant, Phys. Rev. E 70, 051605
      (2004)] produces multigrain structures on atomistic length scale but on diffusive
      time scales. Since individual atoms are resolved but are treated identically it
      is difficult to distinguish the exact position of grain boundaries and defects
      within grains. In order to analyze and visualize the whole grains a two
      dimensional wavelet transform has been developed, which is capable of extracting
      grain boundaries and the lattice orientation of a grain relative to a laboratory
      frame of reference. This transformation makes it possible not only to easily
      visualize the multigrain structure, but also to perform exact measurements on low
      and high-angle boundaries, grain size distributions and boundary-angle
      distributions, which can then be compared to experimental data. The presented
      wavelet transform can also be applied to results of other atomistic simulations,
      e.g., molecular dynamics or granular materials.

PMID- 17025591
TI  - Collective coordinate control of density distributions.
AB  - Real collective density variables C(k) [cf. Eq. 1 3 ] in many-particle systems
      arise from nonlinear transformations of particle positions, and determine the
      structure factor S(k) , where k denotes the wave vector. Our objective is to
      prescribe C(k) and then to find many-particle configurations that correspond to
      such a target C(k) using a numerical optimization technique. Numerical results
      reported here extend earlier one- and two-dimensional studies to include three
      dimensions. In addition, they demonstrate the capacity to control S(k) in the
      neighborhood of |k|=0. The optimization method employed generates multiparticle
      configurations for which S(k) proportional, |k|alpha, |k|<or=K, and alpha=1, 2,
      4, 6, 8, and 10. The case alpha=1 is relevant for the Harrison-Zeldovich model of
      the early universe, for superfluid 4He, and for jammed amorphous sphere packings.
      The analysis also provides specific examples of interaction potentials whose
      classical ground states are configurationally degenerate and disordered.

PMID- 17025592
TI  - Systematic derivation of coarse-grained fluctuating hydrodynamic equations for
      many Brownian particles under nonequilibrium conditions.
AB  - We study the statistical properties of many Brownian particles under the
      influence of both a spatially homogeneous driving force and a periodic potential
      with period l in a two-dimensional space. In particular, we focus on two
      asymptotic cases lint<<l and lint>>l , where lint represents the interaction
      length between two particles. We derive fluctuating hydrodynamic equations
      describing the evolution of a coarse-grained density field defined on scales much
      larger than l for both cases. Using the obtained equations, we calculate the
      equal-time correlation functions of the density field to the lowest order of the
      interaction strength. We find that the system exhibits long-range correlation of
      the type r-d (d=2) for the case lint>>l , while no such behavior is observed for
      the case lint<<l .

PMID- 17025593
TI  - Critical dynamics of phase transition driven by dichotomous Markov noise.
AB  - An Ising spin system under the critical temperature driven by a dichotomous
      Markov noise (magnetic field) with a finite correlation time is studied both
      numerically and theoretically. The order parameter exhibits a transition between
      two kinds of qualitatively different dynamics, symmetry-restoring and symmetry
      breaking motions, as the noise intensity is changed. There exist regions called
      channels where the order parameter stays for a long time slightly above its
      critical noise intensity. Developing a phenomenological analysis of the dynamics,
      we investigate the distribution of the passage time through the channels and the
      power spectrum of the order parameter evolution. The results based on the
      phenomenological analysis turn out to be in quite good agreement with those of
      the numerical simulation.

PMID- 17025594
TI  - Inhomogeneous melting in anisotropically confined two-dimensional clusters.
AB  - Molecular dynamic simulations are performed to investigate the melting process of
      two-dimensional clusters of classical charged particles trapped in an anisotropic
      parabolic potential. The confined particles interact through a repulsive
      potential. We find that the eccentricity of the confinement potential strongly
      affects the melting pattern of such clusters. Increasing the eccentricity of the
      confinement potential drives the system through three different melting regimes.
      Inhomogeneous melting is the typical melting process for anisotropically confined
      clusters and its appearance in small systems occurs in a distinct form called
      here internal intershell melting. The latter involves only particles in the
      center of the cluster while particles on the far left and right of the cluster
      are still ordered having a much higher melting temperature. Using the Lindemann's
      criterion the melting temperatures are determined as a function of the different
      parameters. The internal intershell melting process is found for both long-range
      (i.e., logarithmic) and short-range (i.e., screened Coulomb) interparticle
      interaction. Decreasing the range of the interparticle interaction increases the
      eccentricity of the confinement potential for which internal intershell melting
      can occur.

PMID- 17025595
TI  - Thermodynamics and dynamics of the two-scale spherically symmetric Jagla ramp
      model of anomalous liquids.
AB  - Using molecular dynamics simulations, we study the Jagla model of a liquid which
      consists of particles interacting via a spherically symmetric two-scale potential
      with both repulsive and attractive ramps. This potential displays anomalies
      similar to those found in liquid water, namely expansion upon cooling and an
      increase of diffusivity upon compression, as well as a liquid-liquid (LL) phase
      transition in the region of the phase diagram accessible to simulations. The LL
      coexistence line, unlike in tetrahedrally coordinated liquids, has a positive
      slope, because of the Clapeyron relation, corresponding to the fact that the high
      density phase (HDL) is more ordered than low density phase (LDL). When we cool
      the system at constant pressure above the critical pressure, the thermodynamic
      properties rapidly change from those of LDL-like to those of HDL-like upon
      crossing the Widom line. The temperature dependence of the diffusivity also
      changes rapidly in the vicinity of the Widom line, namely the slope of the
      Arrhenius plot sharply increases upon entering the HDL domain. The properties of
      the glass transition are different in the two phases, suggesting that the less
      ordered phase is fragile, while the more ordered phase is strong, which is
      consistent with the behavior of tetrahedrally coordinated liquids such as water
      silica, silicon, and BeF2.

PMID- 17025596
TI  - Inflow versus outflow zero-temperature dynamics in one dimension.
AB  - It has been suggested that Glauber (inflow) and Sznajd (outflow) zero-temperature
      dynamics for the one-dimensional Ising ferromagnet with nearest-neighbor
      interactions are equivalent. Here we compare the two dynamics from the analytical
      and computational points of view. We use the method of mapping an Ising spin
      system onto the dimer RSA model and show that already this simple mapping allows
      us to see the differences between inflow and outflow zero-temperature dynamics.
      Then we investigate both dynamics with synchronous, partially synchronous, and
      random sequential updating using the Monte Carlo technique and compare both
      dynamics in the number of persistent spins, clusters, mean relaxation time, and
      relaxation time distribution.

PMID- 17025597
TI  - Spatial organization and evolution period of the epidemic model using cellular
      automata.
AB  - We investigate epidemic models with spatial structure based on the cellular
      automata method. The construction of the cellular automata is from the study by
      Weimar and Boon about the reaction-diffusion equations [Phys. Rev. E 49, 1749
      (1994)]. Our results show that the spatial epidemic models exhibit the
      spontaneous formation of irregular spiral waves at large scales within the domain
      of chaos. Moreover, the irregular spiral waves grow stably. The system also shows
      a spatial period-2 structure at one dimension outside the domain of chaos. It is
      interesting that the spatial period-2 structure will break and transform into a
      spatial synchronous configuration in the domain of chaos. Our results confirm
      that populations embed and disperse more stably in space than they do in
      nonspatial counterparts.

PMID- 17025598
TI  - Crossover between Ising and XY -like behavior in the off-equilibrium kinetics of
      the one-dimensional clock model.
AB  - We study the phase-ordering kinetics following a quench to a final temperature Tf
      of the one-dimensional p-state clock model. We show the existence of a critical
      value pc=4, where the properties of the dynamics change. At Tf=0, for p<or=pc the
      dynamics is analogous to that of the kinetic Ising model, characterized by
      Brownian motion and annihilation of interfaces. Dynamical scaling is obeyed with
      the same dynamical exponents and scaling functions of the Ising model. For p>pc,
      instead, the dynamics is dominated by a texture mechanism analogous to the one
      dimensional XY model and dynamical scaling is violated. During the phase-ordering
      process at Tf>0, before equilibration occurs, a crossover between an early XY
      like regime and a late Ising-like dynamics is observed for p>pc.

PMID- 17025599
TI  - Void percolation and conduction of overlapping ellipsoids.
AB  - The void percolation and conduction problems for equisized overlapping ellipsoids
      of revolution are investigated using the discretization method. The method is
      validated by comparing the estimated percolation threshold of spheres with the
      precise result found in literature. The technique is then extended to determine
      the threshold of void percolation as a function of the geometric aspect ratio of
      ellipsoidal particles. The finite element method is also applied to evaluate the
      equivalent conductivity of the void phase in the system. The results confirm that
      there are no universalities for void percolation threshold and conductivity in
      particulate systems, and these properties are clearly dependent on the
      geometrical shape of particles. As a consequence, void percolation and conduction
      associated with ellipsoidal particles of large aspect ratio should be treated
      differently from spheres.

PMID- 17025600
TI  - Critical behavior and synchronization of discrete stochastic phase-coupled
      oscillators.
AB  - Synchronization of stochastic phase-coupled oscillators is known to occur but
      difficult to characterize because sufficiently complete analytic work is not yet
      within our reach, and thorough numerical description usually defies all
      resources. We present a discrete model that is sufficiently simple to be
      characterized in meaningful detail. In the mean-field limit, the model exhibits a
      supercritical Hopf bifurcation and global oscillatory behavior as coupling
      crosses a critical value. When coupling between units is strictly local, the
      model undergoes a continuous phase transition that we characterize numerically
      using finite-size scaling analysis. In particular, we explicitly rule out
      multistability and show that the onset of global synchrony is marked by
      signatures of the XY universality class. Our numerical results cover dimensions
      d=2, 3, 4, and 5 and lead to the appropriate XY classical exponents beta and nu,
      a lower critical dimension dlc=2, and an upper critical dimension duc=4.

PMID- 17025601
TI  - Spectral correlations of fractional Brownian motion.
AB  - Fractional Brownian motion (fBm) is a ubiquitous nonstationary model for many
      physical processes with power-law time-averaged spectra. In this paper, we
      exploit the nonstationarity to derive the full spectral correlation structure of
      fBm. Starting from the time-varying correlation function, we derive two different
      time-frequency spectral correlation functions (the ambiguity function and the
      Kirkwood-Rihaczek spectrum), and one dual-frequency spectral correlation
      function. The dual-frequency spectral correlation has a surprisingly simple
      structure, with spectral support on three discrete lines. The theoretical
      predictions are verified by spectrum estimates of Monte Carlo simulations and of
      a time series of earthquakes with a magnitude of 7 and higher.

PMID- 17025602
TI  - Aging and intermittency in a p-spin model of a glass.
AB  - We numerically analyze the statistics of the heat flow between an aging system
      and its thermal bath, following a method proposed and tested for a spin-glass
      model in a recent paper [P. Sibani and H. J. Jensen, Europhys. Lett. 69, 563
      (2005)]. The present system, which lacks quenched randomness, consists of Ising
      spins located on a cubic lattice, with each plaquette contributing to the total
      energy the product of the four spins located at its corners. Similarly to our
      previous findings, energy leaves the system in rare but large, so-called
      intermittent, bursts which are embedded in reversible and equilibriumlike
      fluctuations of zero average. The intermittent bursts, or quakes, dissipate the
      excess energy trapped in the initial state at a rate which falls off with the
      inverse of the age. This strongly heterogeneous dynamical picture is explained
      using the idea that quakes are triggered by energy fluctuations of record size,
      which occur independently within a number of thermalized domains. From the
      temperature dependence of the width of the reversible heat fluctuations we
      surmise that these domains have an exponential density of states. Finally, we
      show that the heat flow consists of a temperature independent term and a term
      with an Arrhenius temperature dependence. Microscopic dynamical and structural
      information can thus be extracted from numerical intermittency data. This type of
      analysis seems now within the reach of time resolved microcalorimetry techniques.

PMID- 17025603
TI  - Anomalous diffusion with linear reaction dynamics: from continuous time random
      walks to fractional reaction-diffusion equations.
AB  - We have revisited the problem of anomalously diffusing species, modeled at the
      mesoscopic level using continuous time random walks, to include linear reaction
      dynamics. If a constant proportion of walkers are added or removed
      instantaneously at the start of each step then the long time asymptotic limit
      yields a fractional reaction-diffusion equation with a fractional order temporal
      derivative operating on both the standard diffusion term and a linear reaction
      kinetics term. If the walkers are added or removed at a constant per capita rate
      during the waiting time between steps then the long time asymptotic limit has a
      standard linear reaction kinetics term but a fractional order temporal derivative
      operating on a nonstandard diffusion term. Results from the above two models are
      compared with a phenomenological model with standard linear reaction kinetics and
      a fractional order temporal derivative operating on a standard diffusion term. We
      have also developed further extensions of the CTRW model to include more general
      reaction dynamics.

PMID- 17025604
TI  - Random-energy model in random fields.
AB  - The random-energy model is studied in the presence of random fields. The problem
      is solved exactly both in the microcanonical ensemble, without recourse to the
      replica method, and in the canonical ensemble using the replica formalism. The
      phase diagrams for bimodal and Gaussian random fields are investigated in detail.
      In contrast to the Gaussian case, the bimodal random field may lead to a
      tricritical point and a first-order transition. An interesting feature of the
      phase diagram is the possibility of a first-order transition from paramagnetic to
      mixed phase.

PMID- 17025605
TI  - Random field Ising model on networks with inhomogeneous connections.
AB  - We study a zero-temperature phase transition in the random field Ising model on
      scale-free networks with the degree exponent gamma. Using an analytic mean-field
      theory, we find that the spins are always in the ordered phase for gamma<3. On
      the other hand, the spins undergo a phase transition from an ordered phase to a
      disordered phase as the dispersion of the random fields increases for gamma>3.
      The phase transition may be either continuous or discontinuous depending on the
      shape of the random field distribution. We derive the condition for the nature of
      the phase transition. Numerical simulations are performed to confirm the results.

PMID- 17025606
TI  - Thermodynamic perturbation theory in fluid statistical mechanics.
AB  - A methodology is proposed that pushes the thermodynamic perturbation theory (TPT)
      from first order to higher order. The second-order correction is superior to a
      macroscopic compressibility (MC) approximation of Barker and Henderson. The
      present third-order TPT performs far better than the original first-order TPT and
      second-order TPT based on the MC approximation for many subfields in fluid
      statistical mechanics, such as predicting excess Helmholtz free energy, excess
      chemical potential, bulk pressure, gas-liquid coexistence, and solid-liquid
      equilibrium of very short-range potential fluids. A nonuniform version of the TPT
      is proposed; it is also shown that the nonuniform third-order TPT performs far
      better than the nonuniform first-order TPT in predicting density profile of
      fluids in critical region. The present report indicates that the TPT still can be
      a "universal" and accurate theoretical tool that has general applicability in
      fluid statistical mechanics, especially in soft-matter physics.

PMID- 17025607
TI  - Percolation in the harmonic crystal and voter model in three dimensions.
AB  - We investigate the site percolation transition in two strongly correlated systems
      in three dimensions: the massless harmonic crystal and the voter model. In the
      first case we start with a Gibbs measure for the potential U=(J2) summation
      operatorx,y[phi(x)-phi(y)]2, x,y Z3, J>0, and phi(x) R, a scalar height variable,
      and define occupation variables rhoh(x)=1 (0) for phi(x)>h (<h). The probability
      p of a site being occupied is then a function of h . In the voter model we
      consider a stationary measure in which each site is either occupied or empty,
      with probability p . In both cases the truncated pair correlation of the
      occupation variables, G(x-y) , decays asymptotically as mid |x-y|-1 . Using some
      Monte Carlo simulation methods and finite-size scaling we find accurate values of
      pc as well as the critical exponents for these systems. The latter are different
      from that of independent percolation in d=3 , as expected from the work of
      Weinrib and Halperin (WH) for the percolation transition of systems with G(r)
      approximately r-a [Phys. Rev. B 27, 413 (1983)]. In particular the correlation
      length exponent nu is very close to the predicted value of 2, supporting the
      conjecture by WH that nu=2/a is exact.

PMID- 17025608
TI  - Recycled noise rectification: an automated Maxwell's daemon.
AB  - The one-dimensional motion of a massless Brownian particle on a symmetric
      periodic substrate can be rectified by reinjecting its driving noise through a
      realistic recycling procedure. If the recycled noise is multiplicatively coupled
      to the substrate, the ensuing feedback system works like a passive Maxwell's
      daemon, capable of inducing a net current that depends on both the delay and the
      autocorrelation times of the noise signals. Extensive numerical simulations show
      that the underlying rectification mechanism is a resonant nonlinear effect: The
      observed currents can be optimized for an appropriate choice of the recycling
      parameters with immediate application to the design of nanodevices for particle
      transport.

PMID- 17025609
TI  - Fokker-Planck equation for particle growth by monomer attachment.
AB  - The population balance equation (PBE) for growth by attachment of a monomeric
      unit is described in the discrete domain by an infinite set of differential
      equations. Transforming the discrete problem into the continuous domain produces
      a series expansion which is usually truncated past the first term. We study the
      effect of this truncation and we show that by including the second-order term one
      obtains a Fokker-Planck approximation of the continuous PBE whose first and
      second moments are exact. We use this truncation to study the asymptotic behavior
      of the variance of the size distribution with growth rate that is a power-law
      function of the particle mass with exponent a . We obtain analytic expressions
      for the variance and show that its asymptotic behavior is different in the
      regimes a<1/2 and a>1/2. These conclusions are corroborated by Monte Carlo
      simulations.

PMID- 17025610
TI  - Ground state overlap and quantum phase transitions.
AB  - We present a characterization of quantum phase transitions in terms of the the
      overlap function between two ground states obtained for two different values of
      external parameters. On the examples of the Dicke and XY models, we show that the
      regions of criticality of a system are marked by the extremal points of the
      overlap and functions closely related to it. Further, we discuss the connections
      between this approach and the Anderson orthogonality catastrophe as well as with
      the dynamical study of the Loschmidt echo for critical systems.

PMID- 17025611
TI  - Elasticity of a system with noncentral potentials.
AB  - We derive expressions for determination of the stress and the elastic constants
      in systems composed of particles interacting via noncentral two-body potentials
      as thermal averages of products of first and second partial derivatives of the
      interparticle potentials and components of the interparticle separation vectors.
      These results are adapted to hard potentials, where the stress and the elastic
      constants are expressed as thermal averages of the components of normals to
      contact surfaces between the particles and components of vectors separating their
      centers. The averages require knowledge of the simultaneous contact probabilities
      of two pairs of particles. We apply the expressions to particles for which a
      contact function can be defined, and demonstrate the feasibility of the method by
      computing the stress and the elastic constants of a two-dimensional system of
      hard ellipses using Monte Carlo simulations.

PMID- 17025612
TI  - Viscosity of a binary mixture: approach to the hydrodynamic limit.
AB  - We have used equilibrium and nonequilibrium molecular dynamics simulations to
      study the solute self-diffusion coefficient and the shear rate dependence of the
      solution viscosity in solutions of model nanocolloidal particles that range in
      mass ratio from mu=1 up to mu=50 and size ratio from s=1 up to s=4.03 at various
      concentrations. The zero shear rate viscosities and the initial rates of shear
      thinning were determined from data in the shear rate region in which the
      suspension is strongly shear thinning while the solvent remains Newtonian or is
      weakly shear thinning. The rate of shear thinning increased dramatically with
      solute volume fraction, regardless of whether the increase was due to increasing
      solute size or increasing the solute concentration. In a series of simulations in
      which the mass ratio was varied while keeping the size ratio fixed at s=1, we
      found that the approach of the viscosities and self-diffusion coefficients to
      their limiting mass ratio independent values was well described by a rather
      simple exponential dependence on mass ratio. The concentration dependence of the
      limiting infinite mass ratio values of the self-diffusion coefficients and zero
      shear rate viscosities were determined, and used to compute the hydrodynamic
      radius RH of the solute particles by various methods. The values of RH that were
      obtained by the different methods were reasonably consistent with each other, and
      indicated that the radius at which the slip boundary condition holds is slightly
      smaller than the cross-interaction radius between the solute and solvent
      particles.

PMID- 17025613
TI  - Thermodynamic properties of inverse power fluids.
AB  - The local scaling behavior of the radial distribution function of the soft sphere
      or inverse power, r-n potential, fluid leads to a formula for the equation of
      state. From this formula different analytic forms for the compressibility factor,
      Z, have been derived. In the first, Z is expressed as a product of three
      functions, the hard sphere equation of state and two other functions
      incorporating the effects of the potential softness. In the second formula, the
      compressibility factor is cast in terms of the position and height of the first
      peak in the radial distribution function. In the final form, Z can be expressed
      as an exponential function which depends entirely on a combination of the virial
      coefficients. In each case Z is an explicit expression which has the correct low
      density limiting behavior and is accurate up to the freezing density for all
      packing fractions and circa n>or=12. Expressions are derived for the various
      component functions required for the different forms of Z, and relations between
      them are established. The compressibility factor manifests a maximum value or
      "ridge" when plotted as contours on the density-softness plane. It starts for the
      softer fluids at lower densities, increases with particle stiffness, and crosses
      the freezing line at n congruent with 33. From the compressibility factor other
      thermodynamic quantities can be obtained and the density-softness dependence of
      the infinite frequency limit elastic properties been determined. A self
      consistent expression is derived for the effective hard sphere packing fraction
      (or equivalently, diameter), valid for all packing fractions and circa n>12. The
      effective hard-sphere diameter is compared with the formulas of Barker and
      Henderson, and Wheatley.

PMID- 17025614
TI  - Three-body interactions and solid-liquid phase equilibria: application of a
      molecular dynamics algorithm.
AB  - The effect of three-body interactions on the solid-liquid phase boundaries of
      argon, krypton, and xenon is investigated via a novel technique that combines
      both nonequilibrium and equilibrium molecular dynamics. The simulations involve
      the evaluation of two- and three-body forces using accurate two-body and three
      body intermolecular potentials. The effect of three-body interactions is to
      substantially increase the coexistence pressure and to lower the densities of
      liquid and solid phases. Comparison with experiment indicates that three-body
      interactions are required to accurately determine the total pressure. In contrast
      to vapor-liquid phase equilibria, the relative contribution of three-body
      interactions to the freezing pressure exceeds the contribution of two-body
      interactions at all temperatures.

PMID- 17025615
TI  - Dynamical signatures of freezing: stable fluids, metastable fluids, and crystals.
AB  - Mean squared displacements and velocity auto correlation functions are calculated
      using molecular dynamics for hard spheres under a range of conditions (i) for the
      equilibrium fluid below freezing; (ii) for the metastable fluid above freezing;
      and (iii) for the hard sphere crystal, both in the metastable region between
      freezing and melting, and in the stable region above melting. In addition,
      simulations are carried out for a metastable Lennard-Jones system. The results
      confirm recent studies that indicated the disappearance of the classical Alder
      long-time tail, and show that they apply to systems other than the metastable
      hard sphere fluid. The implications of these results for our understanding of
      crystallization and the glass transition are discussed.

PMID- 17025616
TI  - Role of structural relaxations and vibrational excitations in the high-frequency
      dynamics of liquids and glasses.
AB  - We present theoretical investigation on the high-frequency collective dynamics in
      liquids and glasses at microscopic length scales and in the terahertz frequency
      region based on the mode-coupling theory for ideal liquid-glass transition. We
      focus on recently investigated issues from inelastic-x-ray-scattering and
      computer-simulation studies for dynamic structure factors and longitudinal and
      transversal current spectra: the anomalous dispersion of the high-frequency sound
      velocity and the nature of the low-frequency excitation called the boson peak. It
      will be discussed how the sound mode interferes with other low-lying modes
      present in the system. Thereby, we provide a systematic explanation of the
      anomalous sound-velocity dispersion in systems--ranging from high temperature
      liquid down to deep inside the glass state--in terms of the contributions from
      the structural-relaxation processes and from vibrational excitations called the
      anomalous-oscillation peak (AOP). A possibility of observing negative dispersion-
      the decrease of the sound velocity upon increase of the wave number--is argued
      when the sound-velocity dispersion is dominated by the contribution from the
      vibrational dynamics. We also show that the low-frequency excitation, observable
      in both of the glass-state longitudinal and transversal current spectra at the
      same resonance frequency, is the manifestation of the AOP. As a consequence of
      the presence of the AOP in the transversal current spectra, it is predicted that
      the transversal sound velocity also exhibits the anomalous dispersion. These
      results of the theory are demonstrated for a model of the Lennard-Jones system.

PMID- 17025617
TI  - Oscillatory ductile compaction dynamics in a cylinder.
AB  - Ductile compaction is common in many natural systems, but the temporal evolution
      of such systems is rarely studied. We observe surprising oscillations in the
      weight measured at the bottom of a self-compacting ensemble of ductile grains.
      The oscillations develop during the first ten hours of the experiment, and
      usually persist through the length of an experiment (one week). The weight
      oscillations are connected to the grain-wall contacts, and are directly
      correlated with the observed strain evolution and the dynamics of grain-wall
      contacts during the compaction. Here, we present the experimental results and
      characteristic time constants of the system, and discuss possible reasons for the
      measured weight oscillations.

PMID- 17025618
TI  - Vibrational dynamics of confined granular materials.
AB  - By means of two-dimensional contact dynamics simulations, we analyze the
      vibrational dynamics of a confined granular layer in response to harmonic
      forcing. We use irregular polygonal grains allowing for strong variability of
      solid fraction. The system involves a jammed state separating passive (loading)
      and active (unloading) states. We show that an approximate expression of the
      packing resistance force as a function of the displacement of the free retaining
      wall from the jamming position provides a good description of the dynamics. We
      study in detail the scaling of displacements and velocities with loading
      parameters. In particular, we find that, for a wide range of frequencies, the
      data collapse by scaling the displacements with the inverse square of frequency,
      the inverse of the force amplitude, and the square of gravity. Interestingly,
      compaction occurs during the extension of the packing, followed by decompaction
      in the contraction phase. We show that the mean compaction rate increases
      linearly with frequency up to a characteristic frequency and then it declines in
      inverse proportion to frequency. The characteristic frequency is interpreted in
      terms of the time required for the relaxation of the packing through collective
      grain rearrangements between two equilibrium states.

PMID- 17025619
TI  - Morphologies of three-dimensional shear bands in granular media.
AB  - We present numerical results on spontaneous symmetry breaking strain localization
      in axisymmetric triaxial shear tests of granular materials. We simulated shear
      band formation using the three-dimensional distinct element method with spherical
      particles. We demonstrate that the local shear intensity, the angular velocity of
      the grains, the coordination number, and the local void ratio are correlated and
      any of them can be used to identify shear bands; however, the latter two are less
      sensitive. The calculated shear band morphologies are in good agreement with
      those found experimentally. We show that boundary conditions play an important
      role. We discuss the formation mechanism of shear bands in the light of our
      observations and compare the results with experiments. At large strains, with
      enforced symmetry, we found strain hardening.

PMID- 17025620
TI  - Effects of bulk dissipation on the critical exponents of a sandpile.
AB  - Bulk dissipation of a sandpile on a square lattice with the periodic boundary
      condition is investigated through a dissipating probability f during each
      toppling process. We find that the power-law behavior is broken for f>10(-1) and
      not evident for 10(-1)}>f>10(-2). In the range 10(-2)>or=f>or=10(-5), numerical
      simulations for the toppling size exponents of all, dissipative, and last waves
      have been studied. Two kinds of definitions for exponents are considered: the
      exponents obtained from the direct fitting of data and the exponents defined by
      the simple scaling. Our result shows that the exponents from these two
      definitions may be different. Furthermore, we propose analytic expressions of the
      exponents for the direct fitting, and it is consistent with the numerical result.
      Finally, we point out that small dissipation drives the behavior of this model
      toward the simple scaling.

PMID- 17025621
TI  - End-wall effects in granular tumblers: From quasi-two-dimensional flow to three
      dimensional flow.
AB  - The flow of granular material in rotating tumblers is confined to a thin flowing
      layer at the free surface in which the particle velocity is primarily streamwise,
      perpendicular to the axis of rotation, with minimal axial motion. Particle
      tracking velocimetry was used to measure the surface velocity for 1 and 2 mm
      glass particles and sand in cylindrical tumblers of various diameters, lengths,
      and rotation rates for a flat continuously flowing surface. End-wall friction
      slows the streamwise surface velocity adjacent to the walls, yet material just
      inward from the end wall flows faster than the material in the center of a long
      tumbler. An axial velocity occurs near the end walls both upstream and downstream
      of the midlength of the flowing layer. Increasing the tumbler diameter and
      corresponding flowing layer length causes the magnitude of the axial and
      streamwise velocity components, as well as the axial thickness of the end-wall
      region, to increase. An increase of end-wall friction slows particles directly
      adjacent to the end wall, further enhancing the axial flow near the end wall.
      Increasing the rotation rate, while still maintaining a flat continuously flowing
      surface, causes a corresponding increase in both the streamwise and axial
      velocities in the tumbler. The boundary flow effects are localized to end walls
      when the axial length of the tumbler (L) is greater than the diameter (D), so
      that the flow in the center region of the tumbler is independent of the end walls
      and hence similar to the conditions at the center of an infinitely long tumbler.
      Decreasing the axial length of the tumbler so that L/D<1 causes the axial
      velocity to decrease as the regions affected by the end walls merge. This also
      leads to a streamwise velocity in quasi-two-dimensional tumblers that can be more
      than twice that at the center of three-dimensional tumblers.

PMID- 17025622
TI  - Effect of rolling on dissipation in fault gouges.
AB  - Sliding and rolling are two outstanding deformation modes in granular media. The
      first one induces frictional dissipation whereas the latter one involves
      deformation with negligible resistance. Using numerical simulations on two
      dimensional shear cells, we investigate the effect of the grain rotation on the
      energy dissipation and the strength of granular materials under quasistatic shear
      deformation. Rolling and sliding are quantified in terms of the so-called
      Cosserat rotations. The observed spontaneous formation of vorticity cells and
      clusters of rotating bearings may provide an explanation for the long standing
      heat flow paradox of earthquake dynamics.

PMID- 17025623
TI  - Creeping granular motion under variable gravity levels.
AB  - In a rotating tumbler that is more than one-half filled with a granular material,
      a core of material forms that should ideally rotate with the tumbler. However,
      the core rotates slightly faster than the tumbler (precession) and decreases in
      size (erosion). The precession and erosion of the core provide a measure of the
      creeping granular motion that occurs beneath a continuously flowing flat surface
      layer. Since the effect of gravity on the subsurface flow has not been explored,
      experiments were performed in a 63% to 83% full granular tumbler mounted in a
      large centrifuge that can provide very high g-levels. Two colors of 0.5 mm glass
      beads were filled side by side to mark a vertical line in the 45 mm radius quasi
      two-dimensional tumbler. The rotation of the core with respect to the tumbler
      (precession) and the decrease in the size of the core (erosion) were monitored
      over 250 tumbler revolutions at accelerations between 1g and 12g. The flowing
      layer thickness is essentially independent of the g-level for identical Froude
      numbers, and the shear rate in the flowing layer increases with increasing g
      level. The degree of core precession increases with the g-level, while the core
      erosion is essentially independent of the g-level. Based on a theory for core
      precession and erosion, the increased precession is likely a consequence of the
      higher shear rate. Core erosion, on the other hand, is related to the creep
      region decay constant, which is connected with slow diffusion in the bed and
      unaffected by gravity.

PMID- 17025624
TI  - Approach to jamming in an air-fluidized granular bed.
AB  - Quasi-two-dimensional bidisperse amorphous systems of steel beads are fluidized
      by a uniform upflow of air, so that the beads roll on a horizontal plane. The
      short-time ballistic motion of the beads is stochastic, with non-Gaussian speed
      distributions and with different average kinetic energies for the two species.
      The approach to jamming is studied as a function of increasing bead area fraction
      and also as a function of decreasing air speed. The structure of the system is
      measured in terms of both the Voronoi tessellation and the pair distribution
      function. The dynamics of the system is measured in terms of both displacement
      statistics and the density of vibrational states. These quantities all exhibit
      tell-tale features as the dynamics become more constrained closer to jamming. In
      particular the pair distribution function and the Voronoi cell shape distribution
      function both develop split peaks. And the mean-squared displacement develops a
      plateau of subdiffusive motion separating ballistic and diffusive regimes. Though
      the system is driven and athermal, this behavior is remarkably reminiscent of
      that in dense colloidal suspensions and supercooled liquids. One possible
      difference is that kurtosis of the displacement distribution peaks at the
      beginning of the subdiffusive regime.

PMID- 17025625
TI  - Particle-size distribution and packing fraction of geometric random packings.
AB  - This paper addresses the geometric random packing and void fraction of
      polydisperse particles. It is demonstrated that the bimodal packing can be
      transformed into a continuous particle-size distribution of the power law type.
      It follows that a maximum packing fraction of particles is obtained when the
      exponent (distribution modulus) of the power law function is zero, which is to
      say, the cumulative finer fraction is a logarithmic function of the particle
      size. For maximum geometric packings composed of sieve fractions or of discretely
      sized particles, the distribution modulus is positive (typically 0<alpha<0.37).
      Furthermore, an original and exact expression is derived that predicts the
      packing fraction of the polydisperse power law packing, and which is governed by
      the distribution exponent, size width, mode of packing, and particle shape only.
      For a number of particle shapes and their packing modes (close, loose), these
      parameters are given. The analytical expression of the packing fraction is
      thoroughly compared with experiments reported in the literature, and good
      agreement is found.

PMID- 17025626
TI  - Capturing patterns and symmetries in chaotic granular flow.
AB  - Segregation patterns formed by time-periodic flow of polydisperse granular
      material (varying in particle size) in quasi-two-dimensional (quasi-2D) tumblers
      capture the symmetries of Poincare sections, stroboscopic maps of the underlying
      flow, derived from a continuum model which contains no information about particle
      properties. We study this phenomenon experimentally by varying the concentration
      of small particles in a bidisperse mixture in quasi-2D tumblers with square and
      pentagonal cross sections. By coupling experiments with an analysis of periodic
      points, we explain the connection between the segregation patterns and the
      dynamics of the underlying flow. Analysis of the eigenvectors and unstable
      manifolds of hyperbolic points shows that lobes of segregated small particles
      stretch from hyperbolic points toward corners of the tumbler, demonstrating the
      connection between regions of chaotic flow and the shape of the segregation
      patterns. Furthermore, unstable manifolds map the shape of lobes of segregated
      particles. The techniques developed here can also be applied to nonpolygonal
      tumblers such as elliptical tumblers, as well as to circular tumblers with time
      periodic forcing.

PMID- 17025627
TI  - Precursors to avalanches in a granular monolayer.
AB  - We investigate the stability of a granular monolayer composed of spherical grains
      on an inclined plate. When the tilt angle alpha increases, some reorganizations
      are observed throughout the pile. The packing fraction rho of the packing evolves
      by successive jumps. Those discontinuous events precede the collapse of the pile
      at a critical angle alphac. The occurrence of precursors before avalanches is
      modeled by stop-and-go motions of blocks due to the competition between sliding
      friction and the Janssen effect [J. Durand, (Springer-Verlag, New York, 2000)].

PMID- 17025628
TI  - Coarsening of axial segregation patterns of slurries in a horizontally rotating
      drum.
AB  - Segregation structures of granular mixtures in rotating drums represent classical
      examples of pattern formation in granular material. We investigate the coarsening
      of axial segregation patterns of slurries in a long horizontally rotating
      cylinder. The dynamics and the three-dimensional geometry of the segregation
      structures are analyzed with optical methods and nuclear magnetic resonance
      imaging. Previous studies have mainly considered global statistical features of
      the pattern dynamics. In order to get insight into driving mechanisms for the
      coarsening process, we focus on the details of the dissolution of individual
      bands. We treat the coarsening as a consequence of interactions of adjacent bands
      in the pattern, which are determined by their geometrical relations. In addition
      to initially homogeneous mixtures, which evolve to spontaneously formed patterns,
      we study the evolution of specially prepared simple initial states. The role of
      the three-dimensional geometry of the axial core in the dissolution process of
      segregation bands is demonstrated. Relations between geometry and dynamic
      processes are established, which may help to find the correct microscopic models
      for the coarsening mechanism.

PMID- 17025629
TI  - Formation and evolution of sediment layers in an aggregating colloidal
      suspension.
AB  - The coupled aggregation and sedimentation of colloidal particles with short-range
      attractions are investigated. Nonadsorbing polymer is used to induce depletion
      interactions between the hard-sphere particles. Gravitational forces, caused by a
      density mismatch between the particles and the suspending fluid, result in the
      sedimentation of particles and aggregates, as well as the compaction and
      rearrangement of the final sediment layer. At low polymer concentrations CP, or
      low initial volume fractions phio, clusters formed during the period of fast
      sedimentation are small, and the structure of the final sediment is dense.
      Conversely, at high CP, or high phio, large clusters form during sedimentation,
      and the resulting sediment structure is significantly less dense, with large void
      volumes. The size of the presediment aggregates depends on CP and phio with a
      functional form that resembles other thermally activated barrier hopping
      processes in colloidal systems, such as the delayed sedimentation of colloidal
      gels. Finally, when the particles are weakly attractive, gravitational stresses
      are found to induce compaction of the sediment over long periods of time.
      However, sediments composed of particles that are strongly attractive resist
      rearrangements and compaction, even when the sediment layers have a relatively
      large amount of free volume.

PMID- 17025630
TI  - Hydrodynamic interactions and Brownian forces in colloidal suspensions: coarse
      graining over time and length scales.
AB  - We describe in detail how to implement a coarse-grained hybrid molecular dynamics
      and stochastic rotation dynamics simulation technique that captures the combined
      effects of Brownian and hydrodynamic forces in colloidal suspensions. The
      importance of carefully tuning the simulation parameters to correctly resolve the
      multiple time and length scales of this problem is emphasized. We systematically
      analyze how our coarse-graining scheme resolves dimensionless hydrodynamic
      numbers such as the Reynolds number Re, which indicates the importance of
      inertial effects, the Schmidt number Sc, which indicates whether momentum
      transport is liquidlike or gaslike, the Mach number, which measures
      compressibility effects, the Knudsen number, which describes the importance of
      noncontinuum molecular effects, and the Peclet number, which describes the
      relative effects of convective and diffusive transport. With these dimensionless
      numbers in the correct regime the many Brownian and hydrodynamic time scales can
      be telescoped together to maximize computational efficiency while still correctly
      resolving the physically relevant processes. We also show how to control a number
      of numerical artifacts, such as finite-size effects and solvent-induced
      attractive depletion interactions. When all these considerations are properly
      taken into account, the measured colloidal velocity autocorrelation functions and
      related self-diffusion and friction coefficients compare quantitatively with
      theoretical calculations. By contrast, these calculations demonstrate that,
      notwithstanding its seductive simplicity, the basic Langevin equation does a
      remarkably poor job of capturing the decay rate of the velocity autocorrelation
      function in the colloidal regime, strongly underestimating it at short times and
      strongly overestimating it at long times. Finally, we discuss in detail how to
      map the parameters of our method onto physical systems and from this extract more
      general lessons-keeping in mind that there is no such thing as a free lunch-that
      may be relevant for other coarse-graining schemes such as lattice Boltzmann or
      dissipative particle dynamics.

PMID- 17025631
TI  - Anomalous surfactant diffusion in a living polymer system.
AB  - Random processes are generally described by Gaussian statistics as formulated by
      the central limit theorem. However, there exists a large number of exceptions to
      this rule that can be found in a variety of fields. Diffusion processes are often
      analyzed by the scaling law <r2> approximately t2beta, where the second moment of
      the diffusion propagator or molecular mean square displacement, <r2>, in the case
      of Gaussian diffusion is proportional to t, i.e., beta=1/2. A deviation from
      Gaussian behavior may be either superdiffusion (beta>1/2) or subdiffusion
      (beta<1/2). In this paper we demonstrate that all three diffusion regimes may be
      observed for the surfactant self-diffusion, on the length scale of 10(-6) m and
      the time scale of 0.02-0.8 s. in a system of wormlike micelles, depending on
      small variations in the sample composition. The self-diffusion is followed by
      pulsed gradient NMR where one not only measures the second moment of the
      diffusion propagator, but actually measures the Fourier transform of the full
      diffusion propagator itself. A generalized diffusion equation in terms of
      fractional time derivatives provides a general description of all the different
      diffusion regimes, and where 1beta can be interpreted as a dynamic fractal
      dimension. Experimentally, we find beta=1/4 and 3/4, in the regimes of sub- and
      superdiffusion, respectively. The physical interpretation of the subdiffusion
      behavior is that the dominating diffusion mechanism corresponds to a lateral
      diffusion along the contour of the wormlike micelles. Superdiffusion is obtained
      near the overlap concentration where the average micellar size is smaller so that
      the center of mass diffusion of the micelles contributes to the transport of
      surfactant molecules.

PMID- 17025632
TI  - Structure and dynamics of a nanocolloidal silica gel dispersion.
AB  - We studied the structure and the dynamics of a nanocolloidal silica gel dispersed
      in an organic solvent [octylcyanobiphenyl (8CB)] as a function of the silica
      density by x-ray intensity fluctuation spectroscopy (XIFS). The silica density of
      the dispersed aerosil gel samples ranged from 0.03 to 0.20 g cm-3 and the
      autocorrelation of the silica scattering was probed over the q range from 0.03 to
      0.15 nm-1 (corresponding to length scales from 42 to 209 nm) at a constant room
      temperature at which 8CB is in the smectic-A phase. The gel structure has a
      fractal dimension in this density range of df approximately 2.15. The time
      autocorrelation functions of the gels show clear density-dependent and complex
      dynamics. The gel relaxation times are very long and become bimodal with
      nonergodic character for densities from 0.10 to 0.16 g cm-3. In this same density
      range, the fluctuation contrast (strength) is a minimum while the relaxation time
      becomes independent of wave vector. Together, these results indicate that there
      is a narrow silica density range for these gels in which the dynamics changes
      dramatically. This suggests a complex phase diagram for the dynamics of aerosil
      gels as a function of densification.

PMID- 17025633
TI  - Finite-element simulation of the depolarization factor of arbitrarily shaped
      inclusions.
AB  - An understanding of the polarization characteristics is a prevailing issue in
      electrostatics and scattering theory and is also vital to the rational design of
      future dielectric nanostructures. In this work, a finite-element methodology has
      been applied to simulate two-phase heterostructures containing a polarizable
      dielectric inclusion. The inclusions investigated can be considered as
      arbitrarily shaped cross sections of infinite three-dimensional objects, where
      the properties and characteristics are invariant along the perpendicular cross
      sectional plane. Given the paucity of experimental and numerical data, we set out
      to systematically investigate the trends that shape and permittivity contrast
      between the inclusion and the host matrix have on the depolarization factor (DF).
      The effect of the first-versus second-order concentration virial coefficient on
      the value of the DF is considered for a variety of inclusion shapes and a large
      set of material properties. Our findings suggest that the DF for such inclusions
      is highly tunable depending on the choice of these parameters. These results can
      provide a useful insight for the design of artificial two-phase heterostructures
      with specific polarization properties.

PMID- 17025634
TI  - Dielectric study of the antiplasticization of trehalose by glycerol.
AB  - Recent measurements have suggested that the antiplasticizing effect of glycerol
      on trehalose can significantly increase the preservation times of proteins stored
      in this type of preservative formulation. In order to better understand the
      physical origin of this phenomenon, we examine the nature of antiplasticization
      in trehalose-glycerol mixtures by dielectric spectroscopy. These measurements
      cover a broad frequency range between 40 Hz to 18 GHz (covering the secondary
      relaxation range of the fragile glass-former trehalose and the primary relaxation
      range of the strong glass-former glycerol) and a temperature (T) range bracketing
      room temperature (220 K to 350 K). The Havriliak-Negami function precisely fits
      our relaxation data and allows us to determine the temperature and composition
      dependence of the relaxation time tau describing a relative fast dielectric
      relaxation process appropriate to the characterization of antiplasticization. We
      observe that increasing the glycerol concentration at fixed T increases tau
      (i.e., the extent of antiplasticization) until a temperature dependent critical
      "plasticization concentration" xwp is reached. At a fixed concentration, we find
      a temperature at which antiplasticization first occurs upon cooling and we
      designate this as the "antiplasticization temperature," Tant. The ratio of the
      tau values for the mixture and pure trehalose is found to provide a useful
      measure of the extent of antiplasticization, and we explore other potential
      measures of antiplasticization relating to the dielectric strength.

PMID- 17025635
TI  - Supercooled water relaxation dynamics probed with heterodyne transient grating
      experiments.
AB  - We report results from a heterodyne-detected transient grating experiment on
      liquid and supercooled water in a wide temperature range, from -17.5 to 90
      degrees C. The measured signal covers an extremely large time window with an
      excellent signal-to-noise ratio that enables the investigation in a single
      experiment of the sound speed and attenuation, thermal diffusivity, and
      temperature dependence of the dielectric constant. The experimental data clearly
      show the effect of the density and the temperature fluctuations on the water
      dielectric function. In order to describe the experimental results, we introduce
      a comprehensive hydrodynamic model taking into account the coupled density and
      temperature variables and their relevance in the definition of the spontaneous
      and forced dielectric variations. We use this model to describe the measured
      signal in transient grating experiments, including the heating and the
      electrostrictive sources produced by the laser excitation. The fitting procedure
      enables the safe extraction of several dynamic properties of liquid and
      supercooled water: the sound velocity and its damping, the thermal diffusivity,
      and the ratio between the dielectric thermodynamic derivatives. The measured
      parameters are compared to the literature data and discussed in the complex
      scenario of water physics.

PMID- 17025636
TI  - Compton scattering study of water versus ice Ih: intra- and intermolecular
      structure.
AB  - The hydrogen-bond geometries in water and polycrystalline ice Ih are studied
      using synchrotron radiation-based Compton scattering data of unprecedented
      statistical accuracy and consistency. By combining the experimental data with
      model calculations utilizing density functional theory, we show that the
      technique provides unique and complementary information on hydrogen bonding in
      water. The comparison of water and ice indicates the necessity of including a
      local intra-intermolecular geometric correlation for water, relating the
      intramolecular O-H bond length to the corresponding hydrogen-bond geometry. By
      using the hydrogen-bond geometries obeying this correlation, we demonstrate a
      further constraint on the angular distortions of the hydrogen bonds in water.

PMID- 17025637
TI  - Phase diagram and structure of colloid-polymer mixtures confined between walls.
AB  - The influence of confinement, due to flat parallel structureless walls, on phase
      separation in colloid-polymer mixtures, is investigated by means of grand
      canonical Monte Carlo simulations. Ultrathin films, with thicknesses between D=3
      10 colloid diameters, are studied. The Asakura-Oosawa model [J. Chem. Phys. 22,
      1255 (1954)] is used to describe the particle interactions. To simulate
      efficiently, a "cluster move" [J. Chem. Phys. 121, 3253 (2004)] is used in
      conjunction with successive umbrella sampling [J. Chem. Phys. 120, 10925 (2004)].
      These techniques, when combined with finite size scaling, enable an accurate
      determination of the unmixing binodal. Our results show that the critical
      behavior of the confined mixture is described by "effective" critical exponents,
      which gradually develop from values near those of the two-dimensional Ising
      model, to those of the three-dimensional Ising model, as D increases. The scaling
      predictions of and Fisher and Nakanishi [J. Chem. Phys. 75, 5875 (1981)] for the
      shift of the critical point are compatible with our simulation results.
      Surprisingly, however, the colloid packing fraction at criticality approaches its
      bulk (D-->infinity) value nonmonotonically, as D is increased. Far from the
      critical point, our results are compatible with the simple Kelvin equation,
      implying a shift of order 1/D in the coexistence colloid chemical potential. We
      also present density profiles and pair distribution functions for a number of
      state points on the binodal, and the influence of the colloid-wall interaction is
      studied.

PMID- 17025638
TI  - Phase-field simulations of velocity selection in rapidly solidified binary
      alloys.
AB  - Time-dependent simulations of two-dimensional isothermal Ni-Cu dendrites are
      simulated using a phase-field model solved with a finite-difference adaptive mesh
      refinement technique. Dendrite tip velocity selection is examined and found to
      exhibit a transition between two markedly different regimes as undercooling is
      increased. At low undercooling, the dendrite tip growth rate is consistent with
      the kinetics of the classical Stefan problem, where the interface is assume to be
      in local equilibrium. At high undercooling, the growth velocity selected
      approaches a linear dependence on melt undercooling, consistent with the
      continuous growth kinetics of Aziz and with a one-dimensional steady-state phase
      field asymptotic analysis of Ahmad [Phys. Rev. E 58, 3436 (1998)]. Our
      simulations are also consistent with other previously observed behaviors of
      dendritic growth as undercooling is increased. These include the transition of
      dendritic morphology to absolute stability and nonequilibrium solute
      partitioning. Our results show that phase-field models of solidification, which
      inherently contain a nonzero interface width, can be used to study the dynamics
      of complex solidification phenomena involving both equilibrium and nonequilibrium
      interface growth kinetics.

PMID- 17025639
TI  - Quasiwetting on spherical solid surfaces by oil-water-amphiphile mixtures.
AB  - We study the wetting behavior on spherical walls by ternary mixtures of oil,
      water, and an amphiphile. We use the Ginzburg-Landau free energy with a single
      order parameter and find that there are different stable structures of the
      interface and that a quasiwetting transition is the mechanism involved in the
      transition among them. We calculate these wetting transitions for two sets of
      parameters in the bulk free energy which are known to show microemulsion
      behavior. The surface transitions are thin-thick first-order transitions
      (continuous transitions are absent), and the phase diagram in surface parameter
      space is constructed. For the first set of bulk parameters water, oil, and a
      microemulsion coexist, and we study the first-order transition where the oil
      phase wets the wall-microemulsion interface and its behavior as the radius of the
      wall becomes large. Therefore, we recover the known wetting transitions on a
      planar wall. In the second set of bulk parameters only water and oil coexist, and
      for some sizes of the solid wall, the oil phase wets the wall-water interface,
      and the phase behavior is extremely rich. We obtain a coexistence of four surface
      phases or two triple points followed by three lines of first-order transitions
      which end at three critical points depending on the radius of the surface. When
      there are micellar metastable solutions in bulk, the behavior of the thickness of
      the wetting layer of the oil phase as the radius of the spherical wall gets
      larger is nonmonotonic. We associate this behavior with the intrinsic micelle
      structure due to the spontaneous curvature of the model.

PMID- 17025640
TI  - Arrested segregative phase separation in capillary tubes.
AB  - Phase separation in a capillary tube with one of the phases fully wetting the
      capillary wall is arrested when the typical size of the phase domains reaches the
      value of the diameter of the tube. The arrested state consists of an alternating
      sequence of concave-capped and convex-capped cylindrical domains, called "plugs,"
      "bridges," or "lenses," of wetting and nonwetting phase, respectively. A
      description of this arrested plug state for an aqueous mixture of two polymer
      solutions is the subject of this work. A phase separating system consisting of
      two incompatible polymers dissolved in water was studied. The phase volume ratio
      was close to unity. The initial state from which plugs evolve is characterized by
      droplets of wetting phase in a continuous nonwetting phase. Experiments show the
      formation of plugs by a pathway that differs from the theoretically well
      described instabilities in the thickness of a fluid thread inside a confined
      fluid cylinder. Plugs appear to form after the wetting layer (the confined fluid
      cylinder) has become unstable after merging of droplet with the wetting layer.
      The relative density of the phases could be set by the addition of salt, enabling
      density matching. As a consequence, the capillary length can in principle be made
      infinitely large and the Bond number (which represents the force of gravity
      relative to the capillary force) zero, without considerably changing the
      interfacial tension. Using the possibility of density matching, the relations
      among capillary length and capillary diameter on the one hand, and the presence
      of plugs and their average size on the other were studied. It was found that
      stable plugs are present when the capillary radius does not exceed a certain
      value, which is probably smaller than the capillary length. However, the average
      plug size is independent of capillary length. At constant capillary length,
      average plug size was found to scale with the capillary diameter to a power 1.3,
      significantly higher than the expected value of 1. Plug sizes had a
      polydispersity between 1.1 and 1.2 for all capillary radii for which this number
      could be reliably determined, suggesting a universal plug size distribution.
      Within plug sequences, size correlations were found between plugs with one to
      three plugs in between. This suggests the presence of an additional length scale.

PMID- 17025641
TI  - In situ and real-time probing of quasicrystal solidification dynamics by
      synchrotron imaging.
AB  - Quasicrystal growth remains an unsolved problem in condensed matter. The dynamics
      of the process is studied by means of synchrotron live imaging all along the
      solidification of icosahedral AlPdMn quasicrystals. The lateral motion of ledges
      driving faceted growth at the solid-melt interface is conclusively shown. When
      the solidification rate is increased, nucleation and free growth of new faceted
      grains occur in the melt due to the significant interface recoil induced by slow
      attachment kinetics. The detailed analysis of the evolution of these grains
      reveals the crucial role of aluminum rejection, both in the poisoning of their
      growth and driving fluid flow.

PMID- 17025642
TI  - Influence of external flows on crystal growth: numerical investigation.
AB  - We use a combined phase-field-lattice-Boltzmann scheme [Medvedev and Kassner,
      Phys. Rev. E 72, 056703 (2005)] to simulate nonfaceted crystal growth from an
      undercooled melt in external flows. Selected growth parameters are determined
      numerically. For growth patterns at moderate to high undercooling and relatively
      large anisotropy, the values of the tip radius and selection parameter plotted as
      a function of the Peclet number fall approximately on single curves. Hence, it
      may be argued that a parallel flow changes the selected tip radius and growth
      velocity solely by modifying (increasing) the Peclet number. This has interesting
      implications for the availability of current selection theories as predictors of
      growth characteristics under flow. At smaller anisotropy, a modification of the
      morphology diagram in the plane of undercooling versus anisotropy is observed.
      The transition line from dendrites to doublons is shifted in favor of dendritic
      patterns, which become faster than doublons as the flow speed is increased, thus
      rendering the basin of attraction of dendritic structures larger. For small
      anisotropy and Prandtl number, we find oscillations of the tip velocity in the
      presence of flow. On increasing the fluid viscosity or decreasing the flow
      velocity, we observe a reduction in the amplitude of these oscillations.

PMID- 17025643
TI  - Capillary wave fluctuations and intrinsic widths of coupled fluid-fluid
      interfaces: an x-ray scattering study of a wetting film on bulk liquid.
AB  - An x-ray specular reflectivity (XR) and off-specular diffuse scattering (XDS)
      study of the coupled thermal capillary fluctuations and the intrinsic profiles of
      two interacting fluid-fluid interfaces is presented. The measurements are carried
      out on complete wetting films of perfluoromethylcyclohexane (PFMC) on the surface
      of bulk liquid eicosane (C20), as a function of film thickness 30<D<160 A. In
      order to facilitate the analysis and interpretation of the data with minimal
      complexity, approximate methods for calculating scattering intensities are
      developed to take into account the subtleties of thermal diffuse scattering from
      layered liquid surfaces. With these methods, the calculations of XR/XDS
      intensities are reduced to a single numerical integration of simple functions in
      real space. In addition, an analytic expression is derived for small-angle XR
      that contains Debye-Waller-like factors with effective capillary roughness and
      takes into account the partial correlations of the two interfaces. The expression
      for the XR is quantitatively accurate so long as the reflection angle is small
      enough that the scattering from interfaces is distinguishable from bulk
      scattering. The results of the XR and XDS data analysis indicate that the
      capillary fluctuations at the two interfaces of the wetting films are partially
      correlated and their coupling is consistent with the van der Waals interactions.
      The relatively large intrinsic width (4 approximately 6A) of the liquid-liquid
      interface observed for thicker films (D greater than or similar to 50 A) is
      comparable to the value expected for the bulk liquid-liquid interface (D-
      >infinity), determined by either the radius of gyration (5.3 A) or the bulk
      correlation length (4.8 A) of the alkane C20. The intrinsic liquid-vapor
      interfacial width is sharper (approximately 2 A) and remains essentially constant
      over the entire probed range of D .

PMID- 17025644
TI  - Point tension in adsorption at a chemically inhomogeneous substrate in two
      dimensions.
AB  - We study adsorption of liquid at a one-dimensional substrate composed of a single
      chemical inhomogeneity of width 2L placed on an otherwise homogeneous, planar,
      solid surface. The excess point free energy eta(L,T) associated with the adsorbed
      layer's inhomogeneity induced by the substrate's chemical structure is calculated
      within exact continuum transfer-matrix approach. It is shown that the way
      eta(L,T) varies with L depends sensitively on the temperature regime. It exhibits
      logarithmic divergence as a function of L in the limit L-->infinity for
      temperatures such that the chemical inhomogeneity is completely wetted by the
      liquid. In the opposite case eta(L,T) converges for large L to 2eta0, where eta0
      is the corresponding point tension, and the dominant L-dependent correction to
      2eta0 decays exponentially. The interaction between the liquid layer
      inhomogeneities at -L and L for the two temperature regimes is discussed and
      compared to earlier mean-field theory predictions.

PMID- 17025645
TI  - Multiscale model for microstructure evolution in multiphase materials:
      Application to the growth of isolated inclusions in presence of elasticity.
AB  - We present a multiscale model based on the classical lattice time-dependent
      density-functional theory to study microstructure evolution in multiphase
      systems. As a first test of the method, we study the static and dynamic
      properties of isolated inclusions. Three cases are explored: elastically
      homogeneous systems, elastically inhomogeneous systems with soft inclusions, and
      elastically inhomogeneous systems with hard inclusions. The equilibrium
      properties of inclusions are shown to be consistent with previous results: both
      homogeneous and hard inclusions adopt a circular shape independent of their size,
      whereas soft inclusions are circular below a critical radius and elliptic above.
      In all cases, the Gibbs-Thomson relation is obeyed, except for a change in the
      prefactor at the critical radius in soft inclusions. Under growth conditions,
      homogeneous inclusions exhibit a Mullins-Sekerka shape instability [W. Mullins
      and R. Sekerka, J. Appl. Phys. 34, 323 (1963)], whereas in inhomogeneous systems,
      the growth of perturbations follows the Leo-Sekerka model [P. Leo and R. Sekerka,
      Acta Metall. 37, 3139 (1989)]. For soft inclusions, the mode instability regime
      is gradually replaced by a tip-growing mechanism, which leads to stable, strongly
      out-of-equilibrium shapes even at very low supersaturation. This mechanism is
      shown to significantly affect the growth dynamics of soft inclusions, whereas
      dynamical corrections to the growth rates are negligible in homogeneous and hard
      inclusions. Finally, due to its microscopic formulation, the model is shown to
      automatically take into account phenomena caused by the presence of the
      underlying discrete lattice: anisotropy of the interfacial energy, anisotropy of
      the kinetics, and preferential excitation of shape perturbations commensurate
      with the rotational symmetry of the lattice.

PMID- 17025646
TI  - Structural transformations of even-numbered n-alkanes confined in mesopores.
AB  - The n-alkanes C12H26, C14H30, and C16H34 have been imbibed and solidified in
      mesoporous Vycor glass with a mean pore diameter of 10 nm. The samples have been
      investigated by x-ray diffractometry and calorimetric measurements. The
      structures and phase sequences have been determined. Apart from a reduction and
      the hysteresis of the melting-freezing transition, pore-confined C12 reproduces
      the liquid-triclinic phase sequence of the bulk material, but for C16 an
      orthorhombic rotator mesophase appears that in the bulk state is absent for C16
      but well known from odd-numbered alkanes of similar length. In pore-confined C14
      this phase shows up on cooling but not on heating.

PMID- 17025647
TI  - Crystal-melt interfacial free energies of hard-dumbbell systems.
AB  - The crystal-melt interfacial free energies of different crystal orientations and
      crystal forms for the hard-dumbbell systems have been calculated directly using a
      multistep thermodynamic perturbation method via nonequilibrium work measurements
      with a cleaving procedure. We found that for the plastic crystal phase, the
      interfacial free energies decrease as the reduced bond length L* increases and
      the anisotropy is very weak as in isotropic systems. On the other hand, for the
      orientationally ordered crystal phase, the interfacial free energies become more
      than three times larger and the anisotropy is about 13%. These results may have
      significant implications for our understanding on the nucleation kinetics in
      molecular systems and the search of optimal conditions of protein
      crystallization.

PMID- 17025648
TI  - Some aspects about the structure of the optically isotropic phase in a bent-core
      liquid crystal: chiral, polar, or steric origin.
AB  - We have studied a bent-core liquid crystal where two different optically
      isotropic phases can be induced by a strong electric field. Depending on the
      field treatment the phases can present optical rotation or be optically inactive.
      The switching dynamics of the phases is studied by means of electrooptic and
      optical second-harmonic generation measurements. It is found that the ground
      state of the phases is locally antiferroelectric. The structure of the phases is
      consistent with a disordered version of the kind of structures recently proposed
      for the smectic blue phase: layered systems with high Gaussian curvature. The
      origin of the smectic layer distortion is discussed. It is concluded that the
      direct reason for the curvature of planes is of steric nature.

PMID- 17025649
TI  - Structural study of a bent-core liquid crystal showing the B1-B2 transition.
AB  - An experimental study of the B1-B2 transition is carried out in a bent-core
      liquid crystal. The study is essentially based on x-ray measurements as a
      function of temperature. The B1-B2 transition is extremely unusual and implies a
      deep structural change from a columnar phase to a lamellar phase. We have found
      that the B1 phase in our compound is similar to the so-called B1 reversed phase,
      with an additional splay of the polarization in the columns. On approaching the
      B2 phase the width of the cross section of the columns increases. The transition
      is clearly first order, with a large hysteresis though the enthalpy content is
      very small. A possible mechanism for the transition is briefly sketched.

PMID- 17025650
TI  - Pulsed addressing of a dual-frequency nematic liquid crystal.
AB  - A continuum theory of dielectric relaxation within liquid crystal materials is
      described and used to model the response of dual frequency materials to single
      pulse voltage waveforms. The equations governing the anisotropic axis (director)
      angle, electric field, and induced polarizations are solved numerically to
      investigate pulsed addressing of a model zenithally bistable liquid crystal
      device. By suitably tailoring the voltage pulse, it is found to be possible to
      switch between both bistable states. For short pulses the high frequency
      components of the leading edge of the voltage pulse excites the perpendicular
      polarization and forces the director to lie parallel to the cell substrates. For
      longer voltage pulses the constant dc component of the voltage pulse excites the
      parallel polarization causing the director to lie perpendicular to the
      substrates. It is also found that reducing rotational viscosity and increasing
      the achievable dielectric anisotropies (particularly the high frequency value)
      can significantly reduce the operating voltages of such a device.

PMID- 17025651
TI  - Order parameter of elongated liquid crystal droplets: the method of retrieval by
      the coherent transmittance data.
AB  - The inverse light-scattering problem for polymer dispersed liquid crystal film is
      considered. An optical method to retrieve the tensor order parameter of liquid
      crystal droplets arranged in a monolayer has been developed. The method is based
      on the measurement of coherent transmission coefficients of film at normal
      illumination and comparison with the results of the direct light-scattering
      problem solution. To find the coherent transmission coefficient, the anomalous
      diffraction approach, and the approximation of effective refractive indices are
      used. The dependence of the tensor order parameter on the applied voltage for
      elongated liquid crystal droplets with the rigidly fixed poles is retrieved by
      the available experimental data. The obtained results are in correlation with the
      results of known visual observations of liquid crystal droplet structure and
      calculations of the director field in droplets with rigidly-fixed poles.

PMID- 17025652
TI  - Competing modes of instability in an electrically driven nematic liquid crystal
      with a small positive dielectric anisotropy.
AB  - Competing modes of electric-field-driven bifurcation have been examined in a
      planarly aligned nematic liquid crystal with a small positive dielectric
      anisotropy and large electrical conductivity. The line of bifurcation into the
      electroconvective state is linear in frequency not only up to the codimension-2
      (C2) point but well beyond. This contrasts with the recent theoretical prediction
      of the absence of further bifurcations within the Freedericksz state, above the
      C2 frequency. Further, in the frequency regime beyond C2, within the space
      filling electroconvective state, a strongly localized dynamical state (SLDS)
      appears at a voltage threshold which again is linear in frequency. Occurrence of
      the SLDS through a secondary forward bifurcation is significant in view of the
      reported observations on the so-called worms, an instability belonging to the
      SLDS, as the first form of convection seen at the primary subcritical
      bifurcation.

PMID- 17025653
TI  - Dynamics of bulk fluctuations in a lamellar phase studied by coherent x-ray
      scattering.
AB  - Using x-ray photon correlation spectroscopy, we studied the layer fluctuations in
      the lamellar phase of an ionic lyotropic system. We measured the relaxation rate
      of in-plane (undulation) fluctuations as a function of the wave vector. Static
      and dynamic results obtained during the same experiment were combined to yield
      the values of both elastic constants of the lamellar phase (compression and
      bending moduli) as well as that of the sliding viscosity. The results are in very
      good agreement with dynamic light-scattering data, validating the use of the
      technique in ordered phases.

PMID- 17025654
TI  - Optical studies on the surface-induced tilted layers in freestanding films of two
      no-layer-shrinkage liquid crystal compounds.
AB  - Null transmission ellipsometry has been employed to study the molecular
      arrangements in freestanding films of two no-layer-shrinkage liquid crystal
      homologous compounds above the bulk smectic A-smectic C* (Sm C*) transition
      temperature. An unusual nonplanar-parallel or nonplanar-antiparallel-parallel
      transition has been observed in both compounds under a proper electric field.
      With the addition of one CH2 group, while the SmC* phase is more stable
      thermally, the magnitude of the critical field needed to induce a parallel
      antiparallel transition decreases dramatically.

PMID- 17025655
TI  - Bulk and surface biaxiality in nematic liquid crystals.
AB  - Nematic liquid crystals possess three different phases: isotropic, uniaxial, and
      biaxial. The ground state of most nematics is either isotropic or uniaxial,
      depending on the external temperature. Nevertheless, biaxial domains have been
      frequently identified, especially close to defects or external surfaces. In this
      paper we show that any spatially varying director pattern may be a source of
      biaxiality. We prove that biaxiality arises naturally whenever the symmetric
      tensor S=(Vn)(Vn)T possesses two distinct nonzero eigenvalues. The eigenvalue
      difference may be used as a measure of the expected biaxiality. Furthermore, the
      corresponding eigenvectors indicate the directions in which the order tensor Q is
      induced to break the uniaxial symmetry about the director n. We apply our general
      considerations to some examples. In particular we show that, when we enforce
      homeotropic anchoring on a curved surface, the order tensor becomes biaxial along
      the principal directions of the surface. The effect is triggered by the
      difference in surface principal curvatures.

PMID- 17025656
TI  - Charged inclusion in nematic liquid crystals.
AB  - We present a general theory of liquid crystals under inhomogeneous electric field
      in a Ginzburg-Landau scheme. The molecular orientation can be deformed by
      electric field when the dielectric tensor is orientation dependent. We then
      investigate the influence of a charged particle on the orientation order in a
      nematic state. The director is aligned either along or perpendicular to the local
      electric field around the charge, depending on the sign of the dielectric
      anisotropy. The deformation becomes stronger with increasing the ratio Ze/R,
      where Ze is the charge and R is the radius of the particle. Numerical analysis
      shows the presence of defects around the particle for large Ze/R. They are
      nanometer-scale defects for microscopic ions. If the dielectric anisotropy is
      positive, a Saturn ring defect appears. If it is negative, a pair of point
      defects appear apart from the particle surface, each being connected to the
      surface by a disclination line segment.

PMID- 17025657
TI  - Entropy-induced separation of star polymers in porous media.
AB  - We present a quantitative picture of the separation of star polymers in a
      solution where part of the volume is influenced by a porous medium. To this end,
      we study the impact of long-range-correlated quenched disorder on the entropy and
      scaling properties of f-arm star polymers in a good solvent. We assume that the
      disorder is correlated on the polymer length scale with a power-law decay of the
      pair correlation function g(r) approximately r-a. Applying the field-theoretical
      renormalization group approach we show in a double expansion in epsilon=4-d and
      delta=4-a that there is a range of correlation strengths delta for which the
      disorder changes the scaling behavior of star polymers. In a second approach we
      calculate for fixed space dimension d=3 and different values of the correlation
      parameter a the corresponding scaling exponents gammaf that govern entropic
      effects. We find that gammaf-1, the deviation of gammaf from its mean field value
      is amplified by the disorder once we increase delta beyond a threshold. The
      consequences for a solution of diluted chain and star polymers of equal molecular
      weight inside a porous medium are that star polymers exert a higher osmotic
      pressure than chain polymers and in general higher branched star polymers are
      expelled more strongly from the correlated porous medium. Surprisingly, polymer
      chains will prefer a stronger correlated medium to a less or uncorrelated medium
      of the same density while the opposite is the case for star polymers.

PMID- 17025658
TI  - Colloid dynamics in semiflexible polymer solutions.
AB  - We investigate the dynamics of monodisperse colloidal polystyrene particles
      suspended in solutions of the semiflexible polymer filamentous actin, over a
      range of filament lengths that either exceed or are substantially less than the
      particle radius. The filament length is controlled by the capping protein
      gelsolin, and particle surface chemistries that minimize the adsorption of
      filaments are used. The particle dynamics are measured on short time scales using
      diffusing wave spectroscopy. A sharp transition in the initial particle
      diffusivity marks the expected shift from a dilute to a tightly entangled polymer
      network as the filament average length increases. In both the dilute and
      entangled regimes, the measured particle dynamics are compared with the theories
      of rodlike and semiflexible polymer solution rheology using the generalized
      Stokes-Einstein relationship. In the dilute limit, the particle dynamics are in
      good agreement with theory. However, in the tightly entangled regime, the
      particle response is consistent with polymer depleted near the surfaces of the
      particles. The magnitude of the depletion layer thickness depends strongly on
      particle size and weakly on filament length. This behavior is in agreement with
      nonlocal entropic repulsions and the loss of conformational entropy associated
      with rodlike molecules near impenetrable particles. These results illustrate the
      use of microrheology as a method to investigate local structure and dynamics in
      colloid-polymer solutions.

PMID- 17025659
TI  - Wetting phase diagrams of a polyacid brush with a triple point.
AB  - The (pre)wetting behavior of an annealed polyelectrolyte (PE) brush by an
      electrolyte solution that is strongly segregated from an apolar phase is
      analyzed. In this complex interface, there are interactions on various length
      scales. There are short-range interactions with the (uncharged) surface, and
      there are interactions on the length scale of the brush height. Using either the
      ionic strength or the water-surface interaction strength as the control
      parameters, it is possible to approach and induce a wetting transition in this
      system. The first-order wetting transition, promoted by favorable short-range
      substrate interactions with the surface, is in competition with the wetting
      transition controlled by the detachment of the fluid interface from the periphery
      of the PE brush. The electric double layer on top of the PE brush contributes
      with a repulsive forces to the disjoining pressure that tends to thicken the
      wetting film, and therefore, the transition in all cases is first order. Various
      phase portraits of the wetting phase diagram are envisioned. One of these
      features the crossing of two prewetting lines. At the crossing point three
      surface states coexist. This triple point is analyzed in some detail with the
      help of a molecular-level self-consistent field model.

PMID- 17025660
TI  - Dynamic heterogeneity in hydrogen-bonded polymers.
AB  - We report on neutron spin echo experiments on hydrogen-bonded polymers and
      compare the experimentally found dynamical structure factor with theoretical
      predictions. Surprisingly, we find that in the melt phase the expected scaling of
      the Rouse dynamics is not satisfied. We propose an explanation based upon the
      large spatial volume occupied by the connecting groups. When the effects of these
      bulky groups on the local friction are taken into account, the usual scaling
      behavior is restored.

PMID- 17025661
TI  - Two system-size-resonance behaviors for calcium signaling: for optimal cell size
      and for optimal network size.
AB  - We have studied the collective calcium signaling behavior of an array of coupled
      N cells, taking into account the internal noises resulting from the small cell
      size V. The system's performance was characterized by the reciprocal coefficient
      of variance (RCV) of the calcium spike train. Two system-size resonances were
      observed, namely, the RCV value shows a clear peak when both N and V are optimal.
      Therefore, an optimal number of cells of optimal size work the best as a whole.

PMID- 17025662
TI  - Role of cohesion in the material description of biofilms.
AB  - Biofilm structure plays an important role in biofilm function and control. It is
      thus important to determine the extent to which mechanics may determine structure
      in biofilms. We consider a generic qualitative constitutive description of
      biofilm incorporating as assumptions a small number of fundamental physical
      properties of biofilm viscoelasticity and cohesion. Implications of cohesive
      energy on biofilm structure are then explored. Steady solutions and energy minima
      are studied and it is demonstrated that cohesion energy leads naturally to a free
      surface film state. It is found that in many circumstances, biofilms could be
      subject to heterogeneity formation via spinodal decomposition. Such material
      heterogeneity may have important implications for structural stability in
      biofilms both on short and long time scales.

PMID- 17025663
TI  - Nonlinear elasticity of an alpha-helical polypeptide: Monte Carlo studies.
AB  - We report on Monte Carlo studies of the elastic properties of the helix-coil
      wormlike chain model of alpha-helical polypeptides. In this model the secondary
      structure enters as a scalar (Ising-like) variable that controls the local chain
      bending modulus. We characterize the nonlinear elastic properties of these
      molecules including their response to applied tensile forces and bending torques
      both individually and in combination. We find a pronounced effect of applied
      torque on the extensional compliance of the molecule and a similar effect of
      tension on the bending compliance. Finally we speculate that the strongly
      nonlinear response of alpha-helical polypeptides to combinations of torque and
      force plays a role in allosteric transitions in proteins.

PMID- 17025664
TI  - Two-angle model and phase diagram for chromatin.
AB  - We have studied the phase diagram for chromatin within the framework of the two
      angle model. Only a rough estimation of the forbidden surface of the phase
      diagram for chromatin was given in a previous work of Schiessel. We revealed the
      fine structure of this excluded-volume borderline numerically and analytically.
      Furthermore, we investigated the Coulomb repulsion of the DNA linkers to compare
      it with the previous results.

PMID- 17025665
TI  - Internal signal transmission in one-way coupled excitable system: noise and
      coupling effects.
AB  - We study the spatiotemporal dynamics of a one-way coupled FitzHugh-Nagumo system
      of twenty neurons, which is subject to external noise at the first neuron. It is
      shown that noise-induced oscillation (NIO) triggered at the first neuron is
      propagated along the chain with noise suppression, such that a rather "regular"
      signal is obtained at the last neuron, which can provide a mechanism for the
      creation of the informative signal in a neural network. Coherence resonance or
      coherence biresonance behavior appears in the transmission of NIO at appropriate
      coupling and the information flow in each neuron can be simultaneously optimized
      at the optimal value of noise.

PMID- 17025666
TI  - Bottleneck-induced transitions in a minimal model for intracellular transport.
AB  - We consider the influence of disorder on the nonequilibrium steady state of a
      minimal model for intracellular transport. In this model particles move
      unidirectionally according to the totally asymmetric exclusion process (TASEP)
      and are coupled to a bulk reservoir by Langmuir kinetics. Our discussion focuses
      on localized point defects acting as a bottleneck for the particle transport.
      Combining analytic methods and numerical simulations, we identify a rich phase
      behavior as a function of the defect strength. Our analytical approach relies on
      an effective mean-field theory obtained by splitting the lattice into two
      subsystems, which are effectively connected exploiting the local current
      conservation. Introducing the key concept of a carrying capacity, the maximal
      current that can flow through the bulk of the system (including the defect), we
      discriminate between the cases where the defect is irrelevant and those where it
      acts as a bottleneck and induces various novel phases (called bottleneck phases).
      Contrary to the simple TASEP in the presence of inhomogeneities, many scenarios
      emerge and translate into rich underlying phase diagrams, the topological
      properties of which are discussed.

PMID- 17025667
TI  - Static and dynamic correlations in a charged membrane.
AB  - We study static and dynamic correlations of two fluctuations, the charge density
      fluctuation and height fluctuation (undulation), on a fluid membrane with a
      finite excess charge in a viscous fluid. For a planar and symmetrical membrane,
      we consider a model Hamiltonian inclusive of the fluctuations at the Gaussian
      level, and construct their equations of motion. Within the model, there exists no
      coupling, either static or dynamic, between the two fluctuations. The correlation
      function of the charge density has a short-range damped oscillation over the size
      of lipid heads due to Coulomb attraction between unlike-charged lipids. Its
      dynamic correlation function is shown to decay much faster in time than that in
      simple diffusion. The correlation function of height undulation, on the other
      hand, has a long-range damped oscillation (bud) over the membrane size, due to
      Coulomb repulsion among the excess charges. As the excess charge density
      increases to a critical value, a bending instability sets in, where a minute
      perturbation on the membrane can cause a large bud to form. Due to the excess
      charge, the dynamic correlation of the undulation decays slowly in time; at the
      critical density of the instability, the decay becomes infinitely slow.

PMID- 17025668
TI  - Limits of high-order perturbation theory in time-domain optical mammography.
AB  - Higher order corrections to the Born approximation in perturbation theory are
      derived in order to improve its performance with the experiments in slablike
      geometry. A general expression of the nth order correction to absorption is
      developed. The cross talking between absorption and scattering is given. The
      convergence for higher orders of perturbation analysis for absorbing inclusions
      was studied. Second order absorption and scattering contributions to the
      transmitted flux are discussed by analyzing the data from forward simulations.
      The validity of the results is proven in the experiments with phantoms simulating
      breast tumors. The significant improvement for the fitted values of the
      absorption is observed. The alternative application of developed formalism as the
      first order theory to treat the multiple inclusions is suggested.

PMID- 17025669
TI  - Breaking bonds in the atomic force microscope: theory and analysis.
AB  - A theoretical framework is developed to analyze molecular bond breaking in
      dynamic force spectroscopy using atomic force microscopy. An analytic expression
      of the observed bond breaking probability as a function of force is obtained in
      terms of the relevant physical parameters. The force-ramp mode is discussed in
      detail, which gives the best framework to extract the relevant physical
      parameters such as the potential depth and its width, if a set of widely
      different force-loading rates are used. We also show that the commonly used
      Ritchie-Evans model is incomplete and that it is only applicable for forces well
      below the maximum permitted by the potential. Statistical complications arising
      from the use of constant velocity experiments are discussed in detail.

PMID- 17025671
TI  - Phase-model analysis of coupled neuronal oscillators with multiple connections.
AB  - Synchronization of the coupled neuronal oscillators with multiple connections of
      different coupling nature is analyzed using the phase-model reduction method.
      Each coupling connection contributes to the dynamic behavior of the system in a
      complex nonlinear fashion. In the phase-model scheme, the contribution of the
      individual connections can be separated in terms of the effective coupling
      functions associated with each connection and a linear superposition of them
      provides the total effective coupling of the coupled system. The case of multiple
      connections with various conduction time delays is also examined, which is shown
      to be capable of promoting synchronization over an ensemble of spatially
      distributed neuronal oscillators in an efficient way.

PMID- 17025670
TI  - Stochastic model of protein receptor trafficking prior to synaptogenesis.
AB  - We present a stochastic model of NMDA ( N-methyl d-aspartate) receptor transport
      along a dendrite prior to synapse formation. Receptors undergo periods of
      intracellular kinesin motor-driven transport along microtubules interspersed with
      periods of cycling to the cell surface through exocytosis or endocytsosis. The
      stochastic dynamics is reduced to a spatially discrete hopping model that
      determines the time-dependent distribution of receptors along the dendrite. We
      also investigate how possible defects in motor-assisted transport can affect this
      distribution.

PMID- 17025672
TI  - Irreversible growth model for virus capsid assembly.
AB  - We model the spontaneous assembly of a capsid (a virus' closed outer shell) from
      many copies of identical units, using entirely irreversible steps and only
      information local to the growing edge. Our model is formulated in terms of (i) an
      elastic Hamiltonian with stretching and bending stiffness and a spontaneous
      curvature, and (ii) a set of rate constants for the addition of new units or
      bonds. An ensemble of highly irregular capsids is generated, unlike the well
      known icosahedrally symmetric viruses, but (we argue) plausible as a way to model
      the irregular capsids of retroviruses such as HIV. We found that (i) the
      probability of successful capsid completion decays exponentially with capsid
      size; (ii) capsid size depends strongly on spontaneous curvature and weakly on
      the ratio of the bending and stretching elastic stiffnesses of the shell; (iii)
      the degree of localization of Gaussian curvature (a measure of facetedness)
      depends heavily on the ratio of elastic stiffnesses.

PMID- 17025673
TI  - Effect of Gd3+ on the colloidal stability of liposomes.
AB  - Lanthanide ions such as La3+ and Gd3+ are well known to have large effects on the
      structure of phospholipid membranes. Unilamellar vesicles of
      dipalmitoylphosphatidylcholine (DPPC) were prepared by sonication method and
      confirmed by transmission electron microscopy. The effects of concentration of
      gadolinium ions Gd3+ on DPPC unilamellar vesicles in aqueous media were studied
      by different techniques. As physical techniques, photon correlation spectroscopy,
      electrophoretic mobility, and differential scanning calorimetry were used. The
      theoretical predictions of the colloidal stability of liposomes were followed
      using the Derjaguin-Landau-Verwey-Overbeek theory. Changes in the size of
      liposomes and high polydispersities values were observed as Gd3+ concentration
      increases, suggesting that this cation induces the aggregation of vesicles.
      Electrophoretic mobility measurements on unilamellar vesicles as a function of
      Gd3+ ion concentration show that the vesicles adsorb Gd3+ ions. Above Gd3+
      concentrations of 0.1 mol dm-3, the zeta potential and light scattering
      measurements indicate the beginning of aggregation process. For comparison with
      similar phospholipids, the zeta potential of phosphatidylcholine interacting with
      Gd3+ was measured, showing an analogous behavior. Differential scanning
      calorimetry has been used to determine the effect of Gd3+ on the transition
      temperature (Tc) and on the enthalpy (DeltaHc) associated with the process.

PMID- 17025674
TI  - Mechanism of smart baroreception in the aortic arch.
AB  - A mechanism is proposed by which the patch of baroreceptors along the inner
      curvature of the arch of the aorta can sense hemodynamic events occurring
      downstream from the aortic arch, in the periphery of the arterial tree. Based on
      a solution of equations governing the elastic movements of the aortic wall, it is
      shown that the pressure distribution along the patch of baroreceptors has the
      same functional form as the distribution of strain along the patch. The
      significance of these findings are discussed, particularly as they relate to the
      possibility of a neuromechanical basis of essential hypertension.

PMID- 17025675
TI  - Theory of self-assembly of microtubules and motors.
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 an
      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. We derive the specific form of the
      interaction kernel from the detailed analysis of microscopic interaction of two
      filaments mediated by a moving molecular motor and extend our results to include
      variable motor density and motor attachment to the substrate.

PMID- 17025676
TI  - Quantitative evaluation of linear and nonlinear methods characterizing
      interdependencies between brain signals.
AB  - Brain functional connectivity can be characterized by the temporal evolution of
      correlation between signals recorded from spatially-distributed regions. It is
      aimed at explaining how different brain areas interact within networks involved
      during normal (as in cognitive tasks) or pathological (as in epilepsy)
      situations. Numerous techniques were introduced for assessing this connectivity.
      Recently, some efforts were made to compare methods performances but mainly
      qualitatively and for a special application. In this paper, we go further and
      propose a comprehensive comparison of different classes of methods (linear and
      nonlinear regressions, phase synchronization, and generalized synchronization)
      based on various simulation models. For this purpose, quantitative criteria are
      used: in addition to mean square error under null hypothesis (independence
      between two signals) and mean variance computed over all values of coupling
      degree in each model, we provide a criterion for comparing performances. Results
      show that the performances of the compared methods are highly dependent on the
      hypothesis regarding the underlying model for the generation of the signals.
      Moreover, none of them outperforms the others in all cases and the performance
      hierarchy is model dependent.

PMID- 17025677
TI  - Singular perturbation analysis of the pore creation transient.
AB  - Electroporation, in which electric pulses create transient pores in the cell
      membrane, is an important technique for drug and DNA delivery. Electroporation
      kinetics is mathematically described by an advection-diffusion boundary value
      problem. This study uses singular perturbation to derive a reduced description of
      the pore creation transient in the form of a single integrodifferential equation
      for the transmembrane voltage Vt. The number of pores and the distribution of
      their radii are computed from Vt. The analysis contains two nonstandard features:
      the use of the voltage deviation to peel away the strong exponential dependence
      of pore creation upon the transmembrane potential, and the autonomous
      approximation of the pore evolution. Comparing the predictions of the reduced
      equation with the simulations of the original problem demonstrates that this
      analysis allows one to predict with good accuracy the number and distribution of
      pores as a function of the electric pulse strength.

PMID- 17025678
TI  - Gap junctions destroy persistent states in excitatory networks.
AB  - Gap junctions between excitatory neurons are shown to disrupt the persistent
      state. The asynchronous state of the network loses stability via a Hopf
      bifurcation and then the active state is destroyed via a homoclinic bifurcation
      with a stationary state. A partial differential equation (PDE) is developed to
      analyze the Hopf and the homoclinic bifurcations. The simplified dynamics are
      compared to a biophysical model where similar behavior is observed. In the low
      noise case, the dynamics of the PDE is shown to be very complicated and includes
      possible chaotic behavior. The onset of synchrony is studied by the application
      of averaging to obtain a simple criterion for destabilization of the asynchronous
      persistent state.

PMID- 17025679
TI  - Tail-induced attraction between nucleosome core particles.
AB  - We study a possible electrostatic mechanism underlying the compaction of DNA
      inside the nuclei of eucaryotes: the tail-bridging effect between nucleosomes,
      the fundamental DNA packaging units of the chromatin complex. As a simple model
      of the nucleosome we introduce the eight-tail colloid, a charged sphere with
      eight oppositely charged, flexible, grafted chains that represent the terminal
      histone tails. We show that our complexes attract each other via the formation of
      chain bridges and contrast this to the effect of attraction via charge patches.
      We demonstrate that the attraction between eight-tail colloids can be tuned by
      changing the fraction of charged monomers on the tails. This suggests a physical
      mechanism of chromatin compaction where the degree of DNA condensation is
      controlled via biochemical means, namely the acetylation and deacetylation of
      lysines in the histone tails.

PMID- 17025680
TI  - Driven lattice gas of dimers coupled to a bulk reservoir.
AB  - We investigate the nonequilibrium steady state of a one-dimensional (1D) lattice
      gas of dimers. The dynamics is described by a totally asymmetric exclusion
      process (TASEP) supplemented by attachment and detachment processes, mimicking
      chemical equilibrium of the 1D driven transport with the bulk reservoir. The
      steady-state phase diagram and current and density profiles are calculated using
      both a refined mean-field theory and extensive stochastic simulations. As a
      consequence of the on-off kinetics, a phase coexistence region arises intervening
      between low and high density phases such that the discontinuous transition line
      of the TASEP splits into two continuous ones. The results of the mean-field
      theory and simulations are found to coincide. We show that the physical picture
      obtained in the corresponding lattice gas model with monomers is robust, in the
      sense that the phase diagram changes quantitatively, but the topology remains
      unaltered. The mechanism for phase separation is identified as generic for a wide
      class of driven 1D lattice gases.

PMID- 17025681
TI  - Codability criterion for picking proteinlike structures from random three
      dimensional configurations.
AB  - We show that the dominant eigenvectors of real protein structural contact
      matrices are highly correlated with their amino acid sequences. These results
      suggests that an ab initio sequence-independent profile exists for every protein
      structure and that this profile is highly effective in differentiating the
      ordering of amino acids in natural protein sequences from random sequences. This
      profile provides a structural code and is a key for understanding the unique
      behavior of protein structures. Using a lattice model, we show that there are
      special codable structures highly separated from random structures in the
      dominant eigenvector space of their structural contact matrices. As an example,
      we show our results provide a good explanation to the "designable principle" of
      protein structures.

PMID- 17025682
TI  - Coexistence of tonic firing and bursting in cortical neurons.
AB  - Sustained neuronal activity can be broadly classified as either tonic firing or
      bursting. These two major patterns of neuronal oscillations are state dependent
      and may coexist. The dynamics and intracellular mechanisms of transitions between
      tonic firing and bursting in cortical networks remain poorly understood. Here we
      describe a detailed two-compartment conductance-based cortical neuron model which
      exhibits bistability with hysteresis between tonic firing and bursting for
      elevated extracellular potassium concentration. The study explains the ionic and
      dynamical mechanisms of burst generation and reveals the conditions underlying
      coexistence of two different oscillatory modes as a function of neuronal
      excitability.

PMID- 17025683
TI  - Exact moments in a continuous time random walk with complete memory of its
      history.
AB  - We present a continuous time generalization of a random walk with complete memory
      of its history [Phys. Rev. E 70, 045101(R) (2004)] and derive exact expressions
      for the first four moments of the distribution of displacement when the number of
      steps is Poisson distributed. We analyze the asymptotic behavior of the
      normalized third and fourth cumulants and identify new transitions in a parameter
      regime where the random walk exhibits superdiffusion. These transitions, which
      are also present in the discrete time case, arise from the memory of the process
      and are not reproduced by Fokker-Planck approximations to the evolution equation
      of this random walk.

PMID- 17025684
TI  - Equilibrium conformation of polymer chains with noncircular cross section.
AB  - In this paper we derive the general equilibrium equations of a polymer chain with
      a noncircular cross section by the variation of the free energy functional. From
      the equilibrium equation of the elastic ribbon we derive analytically the
      equilibrium conformations both of the helical ribbons and the twisted ribbons. We
      find that the pitch angle of the helical ribbons depends on the ratio of the
      torsional rigidity to the bending one. For the twisted ribbons, the rotation rate
      depends on the spontaneous torsion, which is determined by the elastic properties
      of the polymers. Our results for helical and twisted ribbons strongly indicate
      that the formation of these structures is determined by their elastic properties.

PMID- 17025685
TI  - Strong far-field coherent scattering of ultraviolet radiation by
      holococcolithophores.
AB  - By considering the structure of holococcoliths (calcite plates that cover
      holococcolithophores, a haploid phase of the coccolithophore life cycle) as a
      photonic structure, we apply a discrete dipolar approximation to study the light
      backscattering properties of these algae. We show that some holococcolith
      structures have the ability to scatter the ultraviolet radiation. This property
      may represent an advantage for holococcolithophores possessing it, by allowing
      them to live higher in the water column than other coccolithophores.

PMID- 17025686
TI  - Network-based predictions of retail store commercial categories and optimal
      locations.
AB  - I study the spatial organization of retail commercial activities. These are
      organized in a network comprising "antilinks," i.e., links of negative weight.
      From pure location data, network analysis leads to a community structure that
      closely follows the commercial classification of the U.S. Department of Labor.
      The interaction network allows one to build a "quality" index of optimal location
      niches for stores, which has been empirically tested.

PMID- 17025687
TI  - Community detection as an inference problem.
AB  - We express community detection as an inference problem of determining the most
      likely arrangement of communities. We then apply belief propagation and mean
      field theory to this problem, and show that this leads to fast, accurate
      algorithms for community detection.

PMID- 17025688
TI  - Preferential attachment and growth dynamics in complex systems.
AB  - Complex systems can be characterized by classes of equivalency of their elements
      defined according to system specific rules. We propose a generalized preferential
      attachment model to describe the class size distribution. The model postulates
      preferential growth of the existing classes and the steady influx of new classes.
      According to the model, the distribution changes from a pure exponential form for
      zero influx of new classes to a power law with an exponential cut-off form when
      the influx of new classes is substantial. Predictions of the model are tested
      through the analysis of a unique industrial database, which covers both
      elementary units (products) and classes (markets, firms) in a given industry
      (pharmaceuticals), covering the entire size distribution. The model's predictions
      are in good agreement with the data. The paper sheds light on the emergence of
      the exponent tau approximately 2 observed as a universal feature of many
      biological, social and economic problems.

PMID- 17025689
TI  - Local load sharing fiber bundles with a lower cutoff of strength disorder.
AB  - We study the failure properties of fiber bundles with a finite lower cutoff of
      the strength disorder varying the range of interaction between the limiting cases
      of completely global and completely local load sharing. Computer simulations
      revealed that at any range of load redistribution there exists a critical cutoff
      strength where the macroscopic response of the bundle becomes perfectly brittle,
      i.e., linearly elastic behavior is obtained up to global failure, which occurs
      catastrophically after the breaking of a small number of fibers. As an extension
      of recent mean field studies [Phys. Rev. Lett. 95, 125501 (2005)], we demonstrate
      that approaching the critical cutoff, the size distribution of bursts of breaking
      fibers shows a crossover to a universal power law form with an exponent 3/2
      independent of the range of interaction.

PMID- 17025690
TI  - Locus of boundary crisis: expect infinitely many gaps.
AB  - Boundary crisis is a mechanism for destroying a chaotic attractor when one
      parameter is varied. In a two-parameter setting the locus of the boundary crisis
      is associated with curves of homoclinic or heteroclinic bifurcations of periodic
      saddle points. It is known that this locus has nondifferentiable points. We show
      here that the locus of boundary crisis is far more complicated than previously
      reported. It actually contains infinitely many gaps, corresponding to regions (of
      positive measure) where attractors exist.

PMID- 17025691
TI  - Alternative determinism principle for topological analysis of chaos.
AB  - The topological analysis of chaos based on a knot-theoretic characterization of
      unstable periodic orbits has proven to be a powerful method, however knot theory
      can only be applied to three-dimensional systems. Still, the core principles upon
      which this approach is built--determinism and continuity--apply in any dimension.
      We propose an alternative framework in which these principles are enforced on
      triangulated surfaces rather than curves, and we show that in dimension 3 our
      approach numerically predicts the correct topological entropies for periodic
      orbits of the horseshoe map.

PMID- 17025692
TI  - Quantum chaos in the spectrum of operators used in Shor's algorithm.
AB  - We provide compelling evidence for the presence of quantum chaos in the unitary
      part of the operator usually employed in Shor's factoring algorithm. In
      particular we analyze the spectrum of this part after proper desymmetrization and
      show that the fluctuations of the eigenangles as well as the distribution of the
      eigenvector components follow the circular unitary ensemble of random matrices,
      of relevance to quantized chaotic systems that violate time-reversal symmetry.
      However, as the algorithm tracks the evolution of a single state, it is possible
      to employ other operators; in particular, it is possible that the generic quantum
      chaos found above becomes of a nongeneric kind such as is found in the quantum
      cat maps and in toy models of the quantum baker's map.

PMID- 17025693
TI  - Phase-flip bifurcation induced by time delay.
AB  - We present a general bifurcation in the synchronized dynamics of time-delay
      coupled nonlinear oscillators. The relative phase between the oscillators jumps
      from zero to pi as a function of the coupling; this phase-flip bifurcation is
      accompanied by a discontinuous change in the frequency of the synchronized
      oscillators. This phenomenon is of broad relevance, being observed in regimes of
      oscillator death as well as in periodic, quasiperiodic, and chaotic dynamics.
      Time-delay coupling is necessary for the phase-flip bifurcation. We illustrate
      the phenomenon, and present analytical results for paradigmatic nonlinear
      systems. Possible applications are discussed.

PMID- 17025694
TI  - Phase synchronization in time-delay systems.
AB  - Though the notion of phase synchronization has been well studied in chaotic
      dynamical systems without delay, it has not been realized yet in chaotic time
      delay systems exhibiting non-phase-coherent hyperchaotic attractors. In this
      paper we report identification of phase synchronization in coupled time-delay
      systems exhibiting hyperchaotic attractor. We show that there is a transition
      from nonsynchronized behavior to phase and then to generalized synchronization as
      a function of coupling strength. These transitions are characterized by
      recurrence quantification analysis, by phase differences based on a
      transformation of the attractors, and also by the changes in the Lyapunov
      exponents. We have found these transitions in coupled piecewise linear and in
      Mackey-Glass time-delay systems.

PMID- 17025695
TI  - Scaling in magnetohydrodynamic convection at high Rayleigh number.
AB  - The theory of Grossmann and Lohse [J. Fluid Mech. 407, 27 (2000)] is extended to
      include the effect of a magnetic field on convection of an electrically
      conducting fluid. Different scaling laws are obtained depending on whether the
      bulk or the boundary layers make the major contribution to the dissipation.
      Scalings are obtained for both weak and strong magnetic fields. The predictions
      are shown to be in better agreement with experimental data than earlier
      theoretical models.

PMID- 17025696
TI  - Periodic sedimentation in a Stokesian fluid.
AB  - We study the sedimentation of two identical but nonspherical particles
      sedimenting in a Stokesian fluid. Experiments and numerical simulations reveal
      periodic orbits wherein the bodies mutually induce an in-phase rotational motion
      accompanied by periodic modulations of sedimentation speed and separation
      distance. We term these "tumbling orbits" and find that they appear over a broad
      range of body shapes.

PMID- 17025697
TI  - Droplet breakup in microfluidic junctions of arbitrary angles.
AB  - Experiments performed on droplets breaking up in microfluidic junctions of
      various angles are described. A critical length is found that controls the
      breakup process. This quantity depends on the flow geometry only; it is
      independent of the flow conditions and the fluid characteristics. A theory
      assuming small capillary numbers describes well the conditions that govern the
      breakup process.

PMID- 17025698
TI  - Solitons in two-dimensional lattices possessing defects, dislocations, and
      quasicrystal structures.
AB  - Localized nonlinear modes, or solitons, are obtained for the two-dimensional
      nonlinear Schrodinger equation with various external potentials that possess
      large variations from periodicity, i.e., vacancy defects, edge dislocations, and
      quasicrystal structure. The solitons are obtained by employing a spectral fixed
      point computational scheme. Investigation of soliton evolution by direct
      numerical simulations shows that irregular-lattice solitons can be stable,
      unstable, or undergo collapse.

PMID- 17025699
TI  - Wave transport in random systems: multiple resonance character of necklace modes
      and their statistical behavior.
AB  - We present the experimental observation of multiple resonance transport of light
      waves, due to necklace states, in disordered one-dimensional systems.
      Transmission phase measurements allow us to identify these states unambiguously
      and investigate their statistical properties. A theoretical model is developed to
      describe the resonance statistics and the frequency dependance of the
      localization length.

PMID- 17025700
TI  - Hyperdynamics for entropic systems: time-space compression and pair correlation
      function approximation.
AB  - We develop a generalized hyperdynamics method that is able to simulate slow
      dynamics in atomistic general (both energy- and entropy-dominated) systems. We
      show that a few functionals of the pair correlation function, involving two-body
      entropy, form a low-dimensional collective space, which is a good approximation
      that is able to distinguish stable and transitional conformations. A bias
      potential, which raises the energy in stable regions, is constructed on the fly.
      We examine the slow nucleation processes of a Lennard-Jones gas and show that our
      method can generate correct long-time dynamics without prior knowledge.

PMID- 17025701
TI  - Kinetically reduced local Navier-Stokes equations: an alternative approach to
      hydrodynamics.
AB  - An alternative approach, the kinetically reduced local Navier-Stokes (KRLNS)
      equations for the grand potential and the momentum, is proposed for the
      simulation of low Mach number flows. The Taylor-Green vortex flow is considered
      in the KRLNS framework, and compared to the results of the direct numerical
      simulation of the incompressible Navier-Stokes equations. The excellent agreement
      between the KRLNS equations and the incompressible nonlocal Navier-Stokes
      equations for this nontrivial time-dependent flow indicates that the former is a
      viable alternative for computational fluid dynamics at low Mach numbers.

PMID- 17025702
TI  - Condensation in a zero range process on weighted scale-free networks.
AB  - We study the condensation phenomenon in a zero range process on weighted scale
      free networks in order to show how the weighted transport influences the particle
      condensation. Instead of the approach of grand canonical ensemble which is
      generally used in a zero range process, we introduce an alternate approach of the
      mean-field equations to study the dynamics of particle transport. We find that
      the condensation on the scale-free network is easier to occur in the case of
      weighted transport than in the case of weight-free networks. In the weighted
      transport, especially, a dynamical condensation is even possible for the case of
      no interaction among particles, which is impossible in the case of weight-free
      networks.

PMID- 17025703
TI  - Cellular automaton simulation of pedestrian counter flow with different walk
      velocities.
AB  - This paper presents a cellular automaton model without step back for pedestrian
      dynamics considering the human behaviors which can make judgments in some complex
      situations. This model can simulate pedestrian movement with different walk
      velocities through update at different time-step intervals. Two kinds of boundary
      conditions including periodic and open boundary for pedestrian counter flow are
      considered, and their dynamical characteristics are discussed. Simulation results
      show that for periodic boundary condition there are three phases of pedestrian
      patterns, i.e., freely moving phase, lane formation phase, and perfectly stopped
      phase at some certain total density ranges. In the stage of lane formation, the
      phenomenon that pedestrians exceed those with lower walk velocity through a
      narrow walkway can be found. For open boundary condition, at some certain
      entrance densities, there are two steady states of pedestrian patterns; but the
      first is metastable. Spontaneous fluctuations can break the first steady state,
      i.e., freely moving phase, and run into the second steady state, i.e., perfectly
      stopped phase.

PMID- 17025704
TI  - Reaction-diffusion fronts in systems with concentration-dependent diffusivities.
AB  - We examine properties of a reaction front that forms in irreversible reaction
      diffusion systems with concentration-dependent diffusivities. We study two
      different models of such systems and find that in the limit of a vanishingly
      small diffusivity of the reaction product, the reaction front dynamics enters a
      separate universality class, with the front width asymptotically tending to a
      constant value, and the reaction rate at the reaction front center diminishing
      with time t as t(-1/2). This behavior can be also observed in systems with
      nonvanishing (but small) diffusivity of the reaction product at intermediate
      times.

PMID- 17025705
TI  - Finding community structure in networks using the eigenvectors of matrices.
AB  - We consider the problem of detecting communities or modules in networks, groups
      of vertices with a higher-than-average density of edges connecting them. Previous
      work indicates that a robust approach to this problem is the maximization of the
      benefit function known as "modularity" over possible divisions of a network. Here
      we show that this maximization process can be written in terms of the
      eigenspectrum of a matrix we call the modularity matrix, which plays a role in
      community detection similar to that played by the graph Laplacian in graph
      partitioning calculations. This result leads us to a number of possible
      algorithms for detecting community structure, as well as several other results,
      including a spectral measure of bipartite structure in networks and a centrality
      measure that identifies vertices that occupy central positions within the
      communities to which they belong. The algorithms and measures proposed are
      illustrated with applications to a variety of real-world complex networks.

PMID- 17025706
TI  - Nonequilibrium dynamics of language games on complex networks.
AB  - The naming game is a model of nonequilibrium dynamics for the self-organized
      emergence of a linguistic convention or a communication system in a population of
      agents with pairwise local interactions. We present an extensive study of its
      dynamics on complex networks, that can be considered as the most natural
      topological embedding for agents involved in language games and opinion dynamics.
      Except for some community structured networks on which metastable phases can be
      observed, agents playing the naming game always manage to reach a global
      consensus. This convergence is obtained after a time generically scaling with the
      population's size N as t(conv) approximately N(1.4+/-0.1), i.e., much faster than
      for agents embedded on regular lattices. Moreover, the memory capacity required
      by the system scales only linearly with its size. Particular attention is given
      to heterogeneous networks, in which the dynamical activity pattern of a node
      depends on its degree. High-degree nodes have a fundamental role, but require
      larger memory capacity. They govern the dynamics acting as spreaders of
      (linguistic) conventions. The effects of other properties, such as the average
      degree and the clustering, are also discussed.

PMID- 17025707
TI  - Phenomenological models of socioeconomic network dynamics.
AB  - We study a general set of models of social network evolution and dynamics. The
      models consist of both a dynamics on the network and evolution of the network.
      Links are formed preferentially between "similar" nodes, where the similarity is
      defined by the particular process taking place on the network. The interplay
      between the two processes produces phase transitions and hysteresis, as seen
      using numerical simulations for three specific processes. We obtain analytic
      results using mean-field approximations, and for a particular case we derive an
      exact solution for the network. In common with real-world social networks, we
      find coexistence of high and low connectivity phases and history dependence.

PMID- 17025708
TI  - Detecting degree symmetries in networks.
AB  - The surrounding of a vertex in a network can be more or less symmetric. We derive
      measures of a specific kind of symmetry of a vertex which we call degree symmetry
      -the property that many paths going out from a vertex have overlapping degree
      sequences. These measures are evaluated on artificial and real networks.
      Specifically we consider vertices in the human metabolic network. We also measure
      the average degree-symmetry coefficient for different classes of real-world
      network. We find that most studied examples are weakly positively degree
      symmetric. The exceptions are an airport network (having a negative degree
      symmetry coefficient) and one-mode projections of social affiliation networks
      that are rather strongly degree symmetric.

PMID- 17025709
TI  - Criticality on networks with topology-dependent interactions.
AB  - Weighted scale-free networks with topology-dependent interactions are studied. It
      is shown that the possible universality classes of critical behavior, which are
      known to depend on topology, can also be explored by tuning the form of the
      interactions at fixed topology. For a model of opinion formation, simple mean
      field and scaling arguments show that a mapping gamma'=(gamma-mu)(1-mu) describes
      how a shift of the standard exponent gamma of the degree distribution can absorb
      the effect of degree-dependent pair interactions J(ij) proportional to
      (k(i)k(j))(-mu), where k(i) stands for the degree of vertex i. This prediction is
      verified by extensive numerical investigations using the cavity method and Monte
      Carlo simulations. The critical temperature of the model is obtained through the
      Bethe-Peierls approximation and with the replica technique. The mapping can be
      extended to nonequilibrium models such as those describing the spreading of a
      disease on a network.

PMID- 17025710
TI  - Phase transitions in an Ising model on a Euclidean network.
AB  - A one-dimensional network on which there are long-range bonds at lattice
      distances l>1 with the probability P(l) proportional to l(-delta) has been taken
      under consideration. We investigate the critical behavior of the Ising model on
      such a network where spins interact with these extra neighbors apart from their
      nearest neighbors for 0<or=delta<2. It is observed that there is a finite
      temperature phase transition in the entire range. For 0<or=delta<1, finite-size
      scaling behavior of various quantities are consistent with mean-field exponents
      while for 1<or=delta<or=2, the exponents depend on delta. The results are
      discussed in the context of earlier observations on the topology of the
      underlying network.

PMID- 17025711
TI  - Dynamical network model of infective mobile agents.
AB  - A dynamical network (consisting of a time-evolving wiring of interactions among a
      group of random walkers) is introduced to model the spread of an infectious
      disease in a population of mobile individuals. We investigate the main properties
      of this model, and show that peculiar features arise when individuals are allowed
      to perform long-distance jumps. Such peculiarities are captured and conveniently
      quantified by a series of appropriate parameters able to highlight the structural
      differences emerging in the networks when long-distance jumps are combined with
      local random walk processes.

PMID- 17025712
TI  - Weighted scale-free networks in Euclidean space using local selection rule.
AB  - A spatial scale-free network is introduced and studied, whose motivation
      originated in the growing Internet as well as airport networks. We argue that in
      these real-world networks a new node necessarily selects one of its neighboring
      local nodes for connection and is not controlled by preferential attachment as in
      the Barabasi-Albert (BA) model. This observation is mimicked in our model where
      the nodes pop up at randomly located positions in the Euclidean space and are
      connected to one end of the nearest link. In spite of this crucial difference it
      is observed that the leading behavior of our network is like that of the BA
      model. Defining the link weight as an algebraic power of its Euclidean length,
      the weight distribution and the nonlinear dependence of the nodal strength on the
      degree are analytically calculated. It is claimed that a power law decay of the
      link weights with time ensures such nonlinear behavior. Switching off the
      Euclidean space from the same model yields a much simpler definition of the BA
      model where numerical effort grows linearly with N.

PMID- 17025713
TI  - Spread of opinions and proportional voting.
AB  - Election results are determined by numerous social factors that affect the
      formation of opinion of the voters, including the network of interactions between
      them and the dynamics of opinion influence. In this work we study the result of
      proportional elections using an opinion dynamics model similar to simple opinion
      spreading over a complex network. Erdos-Renyi, Barabasi-Albert, regular lattices,
      and randomly augmented lattices are considered as models of the underlying social
      networks. The model reproduces the power law behavior of a number of candidates
      with a given number of votes found in real elections with the correct slope, a
      cutoff for a larger number of votes, and a plateau for a small number of votes.
      It is found that the small world property of the underlying network is
      fundamental for the emergence of the power law regime.

PMID- 17025714
TI  - Exhaustive percolation on random networks.
AB  - We consider propagation models that describe the spreading of an attribute,
      called "damage," through the nodes of a random network. In some systems, the
      average fraction of nodes that remain undamaged vanishes in the large system
      limit, a phenomenon we refer to as exhaustive percolation. We derive scaling law
      exponents and exact results for the distribution of the number of undamaged
      nodes, valid for a broad class of random networks at the exhaustive percolation
      transition and in the exhaustive percolation regime. This class includes
      processes that determine the set of frozen nodes in random Boolean networks with
      in-degree distributions that decay sufficiently rapidly with the number of
      inputs. Connections between our calculational methods and previous studies of
      percolation beginning from a single initial node are also pointed out. Central to
      our approach is the observation that key aspects of damage spreading on a random
      network are fully characterized by a single function, specifying the probability
      that a given node will be damaged as a function of the fraction of damaged nodes.
      In addition to our analytical investigations of random networks, we present a
      numerical example of exhaustive percolation on a directed lattice.

PMID- 17025715
TI  - Extraction and analysis of traffic and topologies of transportation networks.
AB  - The knowledge of real-life traffic patterns is crucial for a good understanding
      and analysis of transportation systems. These data are quite rare. In this paper
      we propose an algorithm for extracting both the real physical topology and the
      network of traffic flows from timetables of public mass transportation systems.
      We apply this algorithm to timetables of three large transportation networks.
      This enables us to make a systematic comparison between three different
      approaches to construct a graph representation of a transportation network; the
      resulting graphs are fundamentally different. We also find that the real-life
      traffic pattern is very heterogenous, in both space and traffic flow intensities,
      which makes it very difficult to approximate the node load with a number of
      topological estimators.

PMID- 17025716
TI  - Experimental investigation of the scaling of columnar joints.
AB  - Columnar jointing is a fracture pattern common in igneous rocks in which cracks
      self-organize into a roughly hexagonal arrangement, leaving behind an ordered
      colonnade. We report observations of columnar jointing in a laboratory analog
      system, desiccated corn starch slurries. Using measurements of moisture density,
      evaporation rates, and fracture advance rates as evidence, we suggest that an
      advective-diffusive system is responsible for the rough scaling behavior of
      columnar joints. This theory explains the order of magnitude difference in scales
      between jointing in lavas and in starches. We investigated the scaling of average
      columnar cross-sectional areas due to the evaporation rate, the analog of the
      cooling rate of igneous columnar joints. We measured column areas in experiments
      where the evaporation rate depended on lamp height and time, in experiments where
      the evaporation rate was fixed using feedback methods, and in experiments where
      gelatin was added to vary the rheology of the starch. Our results suggest that
      the column area at a particular depth is related to both the current conditions,
      and hysteretically to the geometry of the pattern at previous depths. We argue
      that there exists a range of stable column scales allowed for any particular
      evaporation rate.

PMID- 17025717
TI  - Preferential attachment in the growth of social networks: the internet
      encyclopedia Wikipedia.
AB  - We present an analysis of the statistical properties and growth of the free on
      line encyclopedia Wikipedia. By describing topics by vertices and hyperlinks
      between them as edges, we can represent this encyclopedia as a directed graph.
      The topological properties of this graph are in close analogy with those of the
      World Wide Web, despite the very different growth mechanism. In particular, we
      measure a scale-invariant distribution of the in and out degree and we are able
      to reproduce these features by means of a simple statistical model. As a major
      consequence, Wikipedia growth can be described by local rules such as the
      preferential attachment mechanism, though users, who are responsible of its
      evolution, can act globally on the network.

PMID- 17025718
TI  - Traffic of particles in complex networks.
AB  - The study of the information flow through communication networks, such as the
      Internet, is of great importance. In the Internet, information flows in discrete
      units ("packets"), and the capacity of storage and processing of information of
      computers is finite. Thus if there are many packets walking on the network at the
      same time, they will interfere with each other. To understand this, we propose an
      idealized model, in which many particles move randomly on the network, and the
      nodes support limited numbers of particles. The maximum number of packets
      supported by a node can be any positive integer, and can be different for each
      node. We analyze the statistical properties of this model, obtaining analytical
      expressions for the mean occupation of each node, for different network
      topologies. The analytical results are shown to be in agreement with numerical
      simulations.

PMID- 17025719
TI  - Percolation model for growth rates of aggregates and its application for business
      firm growth.
AB  - Motivated by recent empirical studies of business firm growth, we develop a
      dynamic percolation model which captures some of the features of the economical
      system--i.e., merging and splitting of business firms--represented as aggregates
      on a d-dimensional lattice. We find the steady-state distribution of the
      aggregate size and explore how this distribution depends on the model parameters.
      We find that at the critical threshold, the standard deviation of the aggregate
      growth rates, sigma, increases with aggregate size S as sigma approximately
      S(beta), where beta can be explained in terms of the connectedness length
      exponent nu and the fractal dimension d(f), with beta=1(2nud(f)) approximately
      0.20 for d=2 and 0.125 for d-->infinity. The distributions of aggregate growth
      rates have a sharp peak at the center and pronounced wings extending over many
      standard deviations, giving the distribution a tent-shape form--the Laplace
      distribution. The distributions for different aggregate sizes scaled by their
      standard deviations collapse onto the same curve.

PMID- 17025720
TI  - Degree landscapes in scale-free networks.
AB  - We generalize the degree-organizational view of real-world networks with broad
      degree distributions in a landscape analog with mountains (high-degree nodes) and
      valleys (low-degree nodes). For example, correlated degrees between adjacent
      nodes correspond to smooth landscapes (social networks), hierarchical networks to
      one-mountain landscapes (the Internet), and degree-disassortative networks
      without hierarchical features to rough landscapes with several mountains. To
      quantify the topology, we here measure the widths of the mountains and the
      separation between different mountains. We also generate ridge landscapes to
      model networks organized under constraints imposed by the space the networks are
      embedded in, associated to spatial or in molecular networks to functional
      localization.

PMID- 17025721
TI  - Maximum entropy approach to power-law distributions in coupled dynamic-stochastic
      systems.
AB  - Statistical properties of coupled dynamic-stochastic systems are studied within a
      combination of the maximum information principle and the superstatistical
      approach. The conditions at which the Shannon entropy functional leads to power
      law statistics are investigated. It is demonstrated that, from a quite general
      point of view, the power-law dependencies may appear as a consequence of "global"
      constraints restricting both the dynamic phase space and the stochastic
      fluctuations. As a result, at sufficiently long observation times the dynamic
      counterpart is driven into a nonequilibrium steady state whose deviation from the
      usual exponential statistics is given by the distance from the conventional
      equilibrium.

PMID- 17025722
TI  - Exact solutions for models of evolving networks with addition and deletion of
      nodes.
AB  - There has been considerable recent interest in the properties of networks, such
      as citation networks and the worldwide web, that grow by the addition of
      vertices, and a number of simple solvable models of network growth have been
      studied. In the real world, however, many networks, including the web, not only
      add vertices but also lose them. Here we formulate models of the time evolution
      of such networks and give exact solutions for a number of cases of particular
      interest. For the case of net growth and so-called preferential attachment--in
      which newly appearing vertices attach to previously existing ones in proportion
      to vertex degree--we show that the resulting networks have power-law degree
      distributions, but with an exponent that diverges as the growth rate vanishes. We
      conjecture that the low exponent values observed in real-world networks are thus
      the result of vigorous growth in which the rate of addition of vertices far
      exceeds the rate of removal. Were growth to slow in the future--for instance, in
      a more mature future version of the web--we would expect to see exponents
      increase, potentially without bound.

PMID- 17025723
TI  - Variational calculation of the limit cycle and its frequency in a two-neuron
      model with delay.
AB  - We consider a model system of two coupled Hopfield neurons, which is described by
      delay differential equations taking into account the finite signal propagation
      and processing times. When the delay exceeds a critical value, a limit cycle
      emerges via a supercritical Hopf bifurcation. First, we calculate its frequency
      and trajectory perturbatively by applying the Poincare-Lindstedt method. Then,
      the perturbation series are resummed by means of the Shohat expansion in good
      agreement with numerical values. However, with increasing delay, the accuracy of
      the results from the Shohat expansion worsens. We thus apply variational
      perturbation theory (VPT) to the perturbation expansions to obtain more accurate
      results, which moreover hold even in the limit of large delays.

PMID- 17025724
TI  - Waving patterns: a general transition from stationary to moving forced Turing
      structures.
AB  - We perform experiments on the chlorine dioxide-iodine-malonic acid (CDIMA)
      reaction forced with light with a pattern of moving stripes in which the
      spatiotemporal behavior is the oscillating movement of stripes (waving). This
      behavior is seen for different relative wavelengths between stationary and moving
      patterns. Different velocities of forcing may produce different modes of
      relaxation of the pattern in order to get to the natural Turing wavelength.
      Zigzag or Eckhaus instabilities may affect the symmetry of the pattern but do not
      influence the waving movement of stripes.

PMID- 17025725
TI  - Desynchronization in diluted neural networks.
AB  - The dynamical behavior of a weakly diluted fully inhibitory network of pulse
      coupled spiking neurons is investigated. Upon increasing the coupling strength, a
      transition from regular to stochasticlike regime is observed. In the weak
      coupling phase, a periodic dynamics is rapidly approached, with all neurons
      firing with the same rate and mutually phase locked. The strong-coupling phase is
      characterized by an irregular pattern, even though the maximum Lyapunov exponent
      is negative. The paradox is solved by drawing an analogy with the phenomenon of
      "stable chaos," i.e., by observing that the stochasticlike behavior is "limited"
      to an exponentially long (with the system size) transient. Remarkably, the
      transient dynamics turns out to be stationary.

PMID- 17025726
TI  - Predictions of ultraharmonic oscillations in coupled arrays of limit cycle
      oscillators.
AB  - Coupled distinct arrays of nonlinear oscillators have been shown to have a regime
      of high frequency, or ultraharmonic, oscillations that are at multiples of the
      natural frequency of individual oscillators. The coupled array architectures
      generate an in-phase high-frequency state by coupling with an array in an
      antiphase state. The underlying mechanism for the creation and stability of the
      ultraharmonic oscillations is analyzed. A class of interarray coupling is shown
      to create a stable, in-phase oscillation having frequency that increases linearly
      with the number of oscillators, but with an amplitude that stays fairly constant.
      The analysis of the theory is illustrated by numerical simulation of coupled
      arrays of Stuart-Landau limit cycle oscillators.

PMID- 17025727
TI  - Experimental realization of strange nonchaotic attractors in a quasiperiodically
      forced electronic circuit.
AB  - We have identified the three prominent routes, namely Heagy-Hammel,
      fractalization, and intermittency routes, and their mechanisms for the birth of
      strange nonchaotic attractors (SNAs) in a quasiperiodically forced electronic
      system constructed using a negative conductance series LCR circuit with a diode
      both numerically and experimentally. The birth of SNAs by these three routes is
      verified from both experimental and their corresponding numerical data by maximal
      Lyapunov exponents, and their variance, Poincare maps, Fourier amplitude
      spectrum, spectral distribution function, and finite-time Lyapunov exponents.
      Although these three routes have been identified numerically in different
      dynamical systems, the experimental observation of all these mechanisms is
      reported here in a single second order electronic circuit.

PMID- 17025728
TI  - Scale disparities in the complex Swift-Hohenberg equation for lasers.
AB  - The complex Swift-Hohenberg (CSH) equation is a generic order parameter equation
      that applies to many physical systems. In the case of class C lasers, it can be
      obtained from the Maxwell-Bloch equations using the assumptions of slow envelope
      and small detuning. We show that the resulting CSH equation inevitably contains
      different asymptotic order terms, associated with the dominance of the effect of
      dispersion over diffusion. These scale disparities are usually overlooked or
      simply not mentioned in the literature, assuming that a CSH equation with all
      terms of the same order still provides qualitative information. In this paper,
      the asymptotically nonuniform CSH equation is carefully deduced using a simpler
      scaling-free procedure, and a stability analysis of the simplest solutions
      together with some numerical simulations are presented, in which the mentioned
      scale disparities are clearly seen.

PMID- 17025729
TI  - Morphologies of expansion ridges of elastic thin films onto a substrate.
AB  - A model of a thin film elastically attached to a rigid substrate is considered.
      In the case in which the film expands relative to the substrate and assuming
      certain nonlinear elastic behavior of the film, expansion ridges may appear, in
      which the material collapses, and the density is higher on average. By studying
      numerically this process, the possible morphologies of these collapsed regions
      are presented. They range from circular spots and straight stripes, to wiggle
      polygonal patterns and ring-shaped domains. The similarity of some of these
      results with patterns observed in delamination of thin films and biphase
      epitaxial growth is emphasized.

PMID- 17025730
TI  - Propagation of wave modes and antispiral waves in a reaction-diffusion system.
AB  - Since the observation of antispirals by Vanag et al. in a reaction-diffusion
      system, the study of its origin becomes a focus of nonlinear science and pattern
      formation. It was shown that antispirals may exist in a reaction-diffusion system
      when the system is near the onset of Hopf bifurcation. Here, we demonstrate that
      antispiral waves can also exist in a relaxational oscillatory medium, which is
      far from Hopf onset. Furthermore, we clarify the previously unclear concept of
      group velocity in inharmonic nonlinear waves, and prove that the group velocity
      v(g)=domega/dk is physically significant and valid both for excitable media and
      for oscillatory media. From this formula, we identify two types of wave
      propagating fronts: gentle mode front and steep mode front. Finally, we discuss
      the origin of counterpropagating waves and propose necessary conditions for
      antispiral formation. A direct deduction from these criteria is that antispirals
      cannot exist in an excitable medium.

PMID- 17025731
TI  - Conservative chaotic map as a model of quantum many-body environment.
AB  - We study the dynamics of the entanglement between two qubits coupled to a common
      chaotic environment, described by the quantum kicked rotator model. We show that
      the kicked rotator, which is a single-particle deterministic dynamical system,
      can reproduce the effects of a pure dephasing many-body bath. Indeed, in the
      semiclassical limit the interaction with the kicked rotator can be described as a
      random phase kick, so that decoherence is induced in the two-qubit system. We
      also show that our model can efficiently simulate non-Markovian environments.

PMID- 17025732
TI  - Resonant-pattern formation induced by additive noise in periodically forced
      reaction-diffusion systems.
AB  - We report frequency-locked resonant patterns induced by additive noise in
      periodically forced reaction-diffusion Brusselator model. In the regime of 2:1
      frequency-locking and homogeneous oscillation, the introduction of additive
      noise, which is colored in time and white in space, generates and sustains
      resonant patterns of hexagons, stripes, and labyrinths which oscillate at half of
      the forcing frequency. Both the noise strength and the correlation time control
      the pattern formation. The system transits from homogeneous to hexagons, stripes,
      and to labyrinths successively as the noise strength is adjusted. Good frequency
      locked patterns are only sustained by the colored noise and a finite time
      correlation is necessary. At the limit of white noise with zero temporal
      correlation, irregular patterns which are only nearly resonant come out as the
      noise strength is adjusted. The phenomenon induced by colored noise in the forced
      reaction-diffusion system is demonstrated to correspond to noise-induced Turing
      instability in the corresponding forced complex Ginzburg-Landau equation.

PMID- 17025733
TI  - Recurrence time distribution in mushroom billiards with parabolic hat.
AB  - The recurrence time distribution of mushroom billiards with a parabolic-shaped
      hat is investigated. Classical dynamics exhibits sharply divided phase space, and
      the recurrence time distribution obeys the algebraic law like well-known classes
      of billiards. However, due to the existence of a specific type of marginally
      unstable periodic orbits that forms a crossing in phase space, the sticky motion
      occurs not as a simple drift along the straight line. Numerical experiments
      reveal and also theoretical analyses predict that an exponent for the cumulative
      recurrence time distribution approaches 2 in the asymptotic regime, but in a
      relatively small recurrence time scale it significantly deviates from the
      predicted universality, which is explained by the slowdown behavior around a
      crossing point of the periodic orbit family.

PMID- 17025734
TI  - Randomly incomplete spectra and intermediate statistics.
AB  - By randomly removing a fraction of levels from a given spectrum a model is
      constructed that describes a crossover from this spectrum to a Poisson spectrum.
      The formalism is applied to the transitions towards Poisson from random matrix
      theory (RMT) spectra and picket fence spectra. It is shown that the Fredholm
      determinant formalism of RMT extends naturally to describe incomplete RMT
      spectra.

PMID- 17025736
TI  - Lateral instability of stationary spherical reaction balls.
AB  - Three-dimensional stability of stationary reaction balls is investigated in a
      system consisting of an autocatalysis accompanied by a slow decay of the
      autocatalyst. Radially stable stationary spherical structures become unstable to
      three-dimensional perturbations at small decay rate when the radius of the
      reaction ball is sufficiently large and the reactant diffuses faster than the
      autocatalyst. A thorough linear stability analysis and simulations in three
      spatial dimensions are carried out in the simplest system sustaining stationary
      reaction balls.

PMID- 17025735
TI  - Universal properties of two-port scattering, impedance, and admittance matrices
      of wave-chaotic systems.
AB  - Statistical fluctuations in the eigenvalues of the scattering, impedance, and
      admittance matrices of two-port wave-chaotic systems are studied experimentally
      using a chaotic microwave cavity. These fluctuations are universal in that their
      properties are dependent only upon the degree of loss in the cavity. We remove
      the direct processes introduced by the nonideally coupled driving ports through a
      matrix normalization process that involves the radiation-impedance matrix of the
      two driving ports. We find good agreement between the experimentally obtained
      marginal probability density functions (PDFs) of the eigenvalues of the
      normalized impedance, admittance, and scattering matrix and those from random
      matrix theory (RMT). We also experimentally study the evolution of the joint PDF
      of the eigenphases of the normalized scattering matrix as a function of loss.
      Experimental agreement with the theory by Brouwer and Beenakker for the joint PDF
      of the magnitude of the eigenvalues of the normalized scattering matrix is also
      shown.

PMID- 17025737
TI  - Hydraulic permeability of ordered and disordered single-layer arrays of
      cylinders.
AB  - The hydraulic permeability of single-layer fibrous media is studied through two
      dimensional (2D) and three-dimensional Navier-Stokes based flow simulations. As
      simple representations of such materials, one-dimensional arrays of parallel
      cylinders as well as two-dimensional arrays of perpendicularly crossing cylinders
      were used. The distance between the cylinders was either constant (ordered
      layers) or variable (disordered layers). For both 1D and 2D ordered layers, we
      propose a geometrical scaling rule for the hydraulic permeability as a function
      of cylinder radius and solid volume fraction (porosity), which is a modification
      of a scaling rule previously reported by Clague and co-workers. The proposed
      modification is based on theoretical considerations and leads to significantly
      improved correspondence with simulation results. The hydraulic permeability of
      unstructured layers is found to be higher than that of structured layers of equal
      porosity for both 1D and 2D arrays. We propose a single parameter that can be
      easily determined experimentally to characterize the degree of disorder, as well
      as a generally valid correction factor in the proposed geometrical scaling rule
      to account for the influence of disorder on the hydraulic permeability.

PMID- 17025738
TI  - Transient dynamics and nonlinear stability of spatially extended systems.
AB  - As studies of various systems have shown, the sole focus on the eigenvalues in a
      linear stability analysis can be misleading, especially when the dynamics of
      disturbances is characterized by strong transient growth. The aim of this paper
      is to extend the generalized stability analysis, in the context of spatially
      extended systems, by examining the role of the nonlinear terms in the
      destabilization process. The critical noise level leading to destabilization is
      often found to scale as a power of the magnitude of transient amplification. In
      what follows we show that the power law exponent sensitively depends on the type
      of nonlinear terms and their potential for generating self-sustaining noise
      amplification cycles (bootstrapping). We find, however, that the exponents are
      not universal and also depend on the more subtle details of the transient
      dynamics. We also show that the basin of attraction of a spatially uniform state
      is bounded by the stable manifold(s) of nearby saddle(s) which play a major role
      in the transition.

PMID- 17025739
TI  - Stationary solutions and Neumann boundary conditions in the Sivashinsky equation.
AB  - New stationary solutions of the (Michelson) Sivashinsky equation of premixed
      flames are obtained numerically in this paper. Some of these solutions, of the
      bicoalescent type recently described by Guidi and Marchetti, are stable with
      Neumann boundary conditions. With these boundary conditions, the time evolution
      of the Sivashinsky equation in the presence of a moderate white noise is
      controlled by jumps between stationary solutions.

PMID- 17025740
TI  - Linear instability of a coflowing jet under an axial electric field.
AB  - A temporal linear stability analysis is carried out for a coflowing jet with two
      immiscible inviscid liquids under a uniform axial electric field. According to
      the electrical properties of the inner and outer liquids, four cases, i.e., IDOC
      (inner: dielectric; outer: conductor), ICOD (inner: conductor; outer:
      dielectric), ICOC (inner and outer: conductor), and IDOD (inner and outer:
      dielectric), are considered. The analytical dimensionless dispersion relation is
      derived for both axisymmetric and nonaxisymmetric perturbations and is solved for
      axisymmetric ones. Three unstable modes, i.e., the paravaricose, parasinuous and
      transitional modes, are identified in the Rayleigh regime. The influences of the
      axial electric field, liquid electrical properties, and Weber number are studied
      at length. The results show that the axial electric field has a generally
      stabilizing effect on the unstable modes. The effects of the liquid electrical
      properties are quite different but all great for each case. The change of
      dominant mode is detected with the variation of the electric field intensity,
      electrical properties or Weber number. It is found that the parasinuous
      instability is the easiest to realize in IDOC. And the comparison with the
      experiment validates that the parasinuous mode is predominant in coaxial
      electrospray.

PMID- 17025741
TI  - Breathing rogue wave observed in numerical experiment.
AB  - Numerical simulations of the recently derived fully nonlinear equations of motion
      for long-crested water waves [V. P. Ruban, Phys. Rev. E 71, 055303(R) (2005)]
      with quasirandom initial conditions are reported, which show the spontaneous
      formation of a single extreme wave on deep water. This rogue wave behaves in an
      oscillating manner and exists for a relatively long time (many wave periods)
      without significant change of its maximal amplitude.

PMID- 17025742
TI  - Elementary kinematical model of thermal diffusion in liquids and gases.
AB  - An elementary hydrodynamic and Brownian motion model of the thermal diffusivity
      D(T) of a restricted class of binary liquid mixtures, previously proposed by the
      author, is given a more transparent derivation than originally, exposing thereby
      the strictly kinematic-hydrodynamic nature of an important class of
      thermodiffusion separation phenomena. Moreover, it is argued that the solvent's
      thermometric diffusivity alpha appearing in that theory as one of the two
      fundamental parameters governing D(T) should be replaced by the solvent's
      (isothermal) self-diffusivity D(S). In addition, a corrective multiplier of O(1)
      is inserted to reflect the general physicochemical noninertness of the solute
      relative to the solvent, thus enhancing the applicability of the resulting
      formula D(T)=lambdaD(S)beta to "nonideal" solutions. Here, beta is the solvent's
      thermal expansivity and lambda is a term of O(1), insensitive to the
      physicochemical nature of the solute (thus rendering D(T) primarily dependent
      upon only the properties of the solvent). This formula is, on the basis of its
      derivation, presumably valid only under certain idealized, albeit well-defined,
      circumstances. This occurs when the solute molecules are: (i) large compared with
      those of the solvent; and (ii) present only in small proportions relative to
      those of the solvent. When the solute is physicochemically inert, it is expected
      that lambda=1. When these conditions are met, the resulting thermal diffusivity
      of the mixture is, in theory, independent of any and all properties of the
      solute. Moreover, because beta is algebraically signed, the thermal diffusivity
      can either by positive or negative, according as the solvent expands or contracts
      upon being heated. This formula for D(T) is compared with available experimental
      data for selected binary liquid mixtures. Reasonable agreement is found in almost
      all circumstances with lambda near unity, the more so the higher the temperature,
      especially when the solute-solvent mixture properties closely approximate those
      where agreement would be expected and conversely. Finally, it is pointed out that
      for the restricted circumstances described, the formula D(T)=lambdaD(S)beta is
      equally credible for gases. Here, based on gas-kinetic theory, it is possible to
      furnish the theoretical value of lambda. Overall, while spanning a range of about
      five orders of magnitude, the D(T) values given by this elementary formula are
      shown to apply with reasonable accuracy to: (i) liquids (including circumstances
      for which D(T) is negative) as well as gases; (ii) all combinations of solvents
      and solutes tested (the latter including, for example, polymer molecules and
      metallic colloidal particles); and (iii) all sizes of solute molecules, from
      angstroms to submicron.

PMID- 17025743
TI  - Experimental investigation of the dynamics of a vibrating grid in superfluid 4He
      over a range of temperatures and pressures.
AB  - In an earlier paper [Nichol, Phys. Rev. E, 70, 056307 (2004)] some of the present
      authors presented the results of an experimental study of the dynamics of a
      stretched grid driven into vibration at or near its resonant frequency in
      isotopically pure superfluid 4He over a range of pressures at a very low
      temperature, where the density of normal fluid is negligible. In this paper we
      present the results of a similar study, based on a different grid, but now
      including the temperature range where the normal fluid density is no longer
      insignificant. The new grid is very similar to the old one except for a small
      difference in the character of its surface roughness. In many respects the
      results at low temperature are similar to those for the old grid. At low
      amplitudes the results are somewhat history dependent, but in essence there is no
      damping greater than that in vacuo. At a critical amplitude corresponding to a
      velocity of about 50 mms(-1) there is a sudden and large increase in damping,
      which can be attributed to the generation of new vortex lines. Strange shifts in
      the resonant frequency at intermediate amplitudes observed with the old grid are
      no longer seen, however they must therefore have been associated with the
      different surface roughness, or perhaps were due simply to some artifact of the
      old grid, the details of which we are currently unable to determine. With the new
      grid we have studied both the damping at low amplitudes due to excitations of the
      normal fluid, and the dependence of the supercritical damping on temperature. We
      present evidence that in helium at low amplitudes there may be some enhancement
      in the effective mass of the grid in addition to that associated with potential
      flow of the helium. In some circumstances small satellite resonances are seen
      near the main fundamental grid resonance, which are attributed to coupling to
      some other oscillatory system within the experimental cell.

PMID- 17025744
TI  - Long-term persistence of the spatial organization of temperature fluctuation
      lifetime in turbulent air avalanches.
AB  - It has been recently proposed that some natural phenomena, such as sunspot
      occurrence, can be represented by a modulated Markov jitter, which is a high
      frequency Markov signal multiplied by a long-term component. The two parameters
      of this model can be estimated using a nonlinear method based on absolute
      derivatives. This analysis is applied here to a different physical system: the
      temperature time series measured during air avalanches in the vertical access pit
      of an underground quarry. The thermal fluctuations associated with these
      turbulent flows, driven by the external temperature forcing, actually appear as
      another practical realization of a modulated Markov jitter. One parameter of the
      model provides the lifetime of the temperature fluctuations, which can be
      estimated as a function of time and position. The obtained lifetime is of the
      order of 10 to 25 min , and is remarkably constant in time for each sensor,
      independently of the amplitude of the forcing. Furthermore, a significant and
      persistent spatial structure is observed, revealing a long-term intrinsic
      organization of the turbulent air flows in the pit. Such a stable spatial
      organization may reflect a general feature of turbulent phenomena.

PMID- 17025745
TI  - Fundamentals of pair diffusion in kinematic simulations of turbulence.
AB  - We demonstrate that kinematic simulation (KS) of three-dimensional homogeneous
      turbulence produces fluid element pair statistics in agreement with the
      predictions of L F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)]
      even though KS lacks explicit modeling of turbulent sweeping of small eddies by
      large ones. This scaling is most clearly evident in the turbulent diffusivity's
      dependence on rms pair separation and, to a lesser extent, on the pair's travel
      time statistics. It is also shown that kinematic simulation generates a
      probability density function of pair separation which is in good agreement with
      recent theory [S. Goto and J. C. Vassilicos, New J. Phys. 6, 65 (2004)] and with
      the scaling of the rms pair separation predicted by L. F. Richardson [Proc. R.
      Soc. London, Ser. A 110, 709 (1926)]. Finally, the statistical persistence
      hypothesis (SPH) is formulated mathematically and its validity tested in KS. This
      formulation introduces the concept of stagnation point velocities and relates
      these to fluid accelerations. The scaling of accelerations found in kinematic
      simulation supports the SPH, even though KS does not generate a Kolmogorov
      scaling for the acceleration variance (except for a specific case and a limited
      range of outer to inner length-scale ratios). An argument is then presented that
      suggests that the stagnation points in homogeneous isotropic turbulence are on
      average long-lived.

PMID- 17025746
TI  - Influence of helicity on anomalous scaling of a passive scalar advected by the
      turbulent velocity field with finite correlation time: two-loop approximation.
AB  - The influence of helicity on the stability of scaling regimes, on the effective
      diffusivity, and on the anomalous scaling of structure functions of a passive
      scalar advected by a Gaussian solenoidal velocity field with finite correlation
      time is investigated by the field theoretic renormalization group and operator
      product expansion within the two-loop approximation. The influence of helicity on
      the scaling regimes is discussed and shown in the plane of exponents epsilon-eta,
      where epsilon characterizes the energy spectrum of the velocity field in the
      inertial range E proportional to k(1-2epsilon), and eta is related to the
      correlation time at the wave number k, which is scaled as k(-2+eta). The
      restrictions given by nonzero helicity on the regions with stable fixed points
      that correspond to the scaling regimes are analyzed in detail. The dependence of
      the effective diffusivity on the helicity parameter is discussed. The anomalous
      exponents of the structure functions of the passive scalar field which define
      their anomalous scaling are calculated and it is shown that, although the
      separate composite operators which define them strongly depend on the helicity
      parameter, the resulting two-loop contributions to the critical dimensions of the
      structure functions are independent of helicity. Details of calculations are
      shown.

PMID- 17025747
TI  - Bifurcation of droplet flows within capillaries.
AB  - Flows of droplets through networks of microchannels differ significantly from the
      flow of simple fluids. Our report focuses on the paths of individual droplets
      through the simplest possible network: a channel that splits into two arms that
      subsequently recombine. This simple system exhibits complex patterns of flow:
      both periodic and irregular, depending on the frequency at which the drops are
      fed into the "loop." A numerical model explains these results and shows regions
      of regular patterns separated by regions of high complexity. Our results elicit
      new questions regarding the dynamics of flow of discrete elements of fluids
      through networks, and point to potential opportunities and difficulties in the
      design of integrated mini-laboratories operating on droplets.

PMID- 17025748
TI  - Diffusion of test particles in stochastic magnetic fields in the percolative
      regime.
AB  - For stochastic magnetic flux functions with percolative contours the test
      particle transport is investigated. The calculations make use of the stochastic
      Liouville approach. They start from the so-called A-Langevin equations, including
      stochastic magnetic field components and binary collisions. Using the
      decorrelation trajectory method, a relation between the Lagrangian velocity
      correlation function and the Eulerian magnetic field correlation is derived and
      introduced into the Green-Kubo formalism. Finite Larmor radius effects are
      included. Interesting results are presented in the percolation regime
      corresponding to high Kubo numbers. Previous results are found to be limiting
      cases for small Kubo numbers. For different percolative scenarios the diffusion
      is analyzed and strong influences of the percolative structures on the transport
      scaling are found. The finite Larmor radius effects are discussed in detail.
      Numerical simulations of the A-Langevin equation confirm the semianalytical
      predictions.

PMID- 17025749
TI  - Behavior of the electron temperature in nonuniform complex plasmas.
AB  - The response of complex ionized gas systems to the presence of nonuniform
      distribution of charged grains is investigated using a kinetic model. Contrary to
      an existing view that the electron temperature inevitably increases in the grain
      occupied region because of enhanced ionization to compensate for the electrons
      lost to the grains, it is shown that this happens only when the ionizing electric
      field increases in the electron depleted region. The results for two typical
      plasma systems suggest that when the ionizing electric field depends on the
      spatially averaged electron density, the electron temperature in the grain
      containing region can actually decrease.

PMID- 17025750
TI  - Femtosecond interferometry of propagation of a laminar ionization front in a gas.
AB  - We use optical interferometry to investigate ultrafast ionization induced by an
      intense, ultrashort laser pulse propagating in a helium gas. Besides standard
      phase shift information, our interferograms show a localized region of fringe
      visibility depletion (FVD) that moves along the laser propagation axis at luminal
      velocity. We find that such a loss of visibility can be quantitatively explained
      by the ultrafast change of refractive index due to the field ionization of the
      gas in the laser pulse width. We demonstrate that by combining the post facto
      phase shift distribution with the probe pulse transit effect in the ionizing
      region, the analysis of the observed FVD yields significant information on the
      ultrafast dynamics of propagation of the ionization front in the gas.

PMID- 17025751
TI  - Thermoemission (dust-electron) plasmas: theory of neutralizing charges.
AB  - Thermoemission plasma--i.e., a system consisting of dust grains and electrons--is
      studied. In the proposed model, it is assumed that the major part of the
      electronic gas is uniformly distributed in space and the spatial inhomogeneities
      of electronic density exist only near the dust grains. The experimental data,
      well described by the proposed theory, are given.

PMID- 17025752
TI  - Proton acceleration from microdroplet spray by weakly relativistic femtosecond
      laser pulses.
AB  - Angular distribution of protons is measured from ethanol droplet spray irradiated
      by linearly polarized 150 fs laser pulses at an intensity of 1.1 x 10(16)W/cm2.
      Fast protons (with energies >16 keV ) with an anisotropic distribution can be
      observed only in or near the polarization plane of the laser fields, while the
      slow protons (with energies <or=16 keV ) emit with nearly an isotropic
      distribution. Two-dimensional particle-in-cell simulations suggest that three
      groups of protons originate from different acceleration regimes in the laser
      droplet interaction. The first group with the highest energies is accelerated
      backwards by the anisotropic charge-separation field near the front surface
      (laser-droplet interaction side) due to the resonance absorption; the second
      group (forward emission) is generated by the target-normal sheath acceleration
      mechanism; and the third group, with the lowest energies, is accelerated by the
      hydrodynamic expansion of the droplet plasmas.

PMID- 17025753
TI  - Plasma density inside a femtosecond laser filament in air: strong dependence on
      external focusing.
AB  - Our experiment shows that external focusing strongly influences the plasma
      density and the diameter of femtosecond Ti-sapphire laser filaments generated in
      air. The control of plasma filament parameters is suitable for many applications
      such as remote spectroscopy, laser induced electrical discharge, and femtosecond
      laser material interactions. The measurements of the filament showed the plasma
      density increases from 10(15)cm(-3) to 2 x 10(18)cm(-3) when the focal length
      decreases from 380 cm to 10 cm while the diameter of the plasma column varies
      from 30 microm to 90 microm. The experimental results are in good qualitative
      agreement with the results of numerical simulations.

PMID- 17025755
TI  - Analytical description of free-electron-laser oscillations in a perfectly
      synchronized optical cavity.
AB  - We present an analytical description of free-electron-laser (FEL) oscillations in
      a perfectly synchronized optical cavity by solving the one-dimensional FEL
      equations. It is shown that the radiation stored in the cavity eventually evolves
      into an intense few-cycle optical pulse in the high-gain and low-loss regime
      despite the lethargy effect. The evolution of the leading slope of the optical
      pulse, which is defined from the front edge toward the primary peak, is found to
      play an important role in generating the intense few-cycle optical pulse. The
      phase space evolution of electrons which interact with the leading slope is
      solved analytically in a perturbation method, leading to an analytical solution
      for the optical pulse evolution. The peak amplitude and the pulse length at
      saturation are found to scale with the electron beam density and optical cavity
      loss. Those scalings agree well with the intense few-cycle pulses recently
      observed in a high-power FEL.

PMID- 17025754
TI  - Approach for simultaneous measurement of two-dimensional angular distribution of
      charged particles. II. Deceleration and focusing of wide-angle beams using a
      curved mesh lens.
AB  - Recently, it was shown that using an ellipsoidal mesh in an einzel-type lens,
      spherical aberration can be corrected over a wide acceptance angle of up to 120
      degrees. The present paper creates the possibility for beam analysis by achieving
      dramatic improvements in deceleration lens capabilities. This provides a scheme
      for simultaneous angular distribution measurement suitable for application to
      high-energy charged-particle beams up to around 10 keV. We consider the behavior
      of wide-angle charged-particle beams in electrostatic fields given by simple
      solutions of the Laplace equation, starting with a discussion on a spherically
      symmetric deceleration field. A beam focusing over a wide acceptance angle of 100
      degrees is found in a special spherically symmetric field. However, in many cases
      of the spherically symmetric field, focusing of wide-angle beams is obstructed by
      the presence of spherical aberration. We show that the spherical aberration can
      be corrected by two kinds of deformation of the spherically symmetric field, a
      deformation of the field under a spherical boundary condition and an ellipsoidal
      deformation of the field. We study practical realization of such fields under the
      use of a few electrodes and a curved mesh (spherical or ellipsoidal mesh). Some
      variations of the arrangement of electrodes are considered, and simple designs of
      deceleration lenses with wide acceptance angles of up to 120 degrees are
      obtained. Here fine focusing of wide-angle beams can be achieved in a three
      electrode deceleration lens with an ellipsoidal mesh.

PMID- 17025756
TI  - Raman and Thompson regimes of amplification in a wiggler with noncollinear laser
      and electron beams.
AB  - The collective and single-electron amplification regimes of a noncollinear free
      electron laser (FEL) are studied within the framework of dispersion equations. In
      the limit of small-signal gain the growth rates and the conditions for self
      amplified excitations are found for the collective (Raman) and single-electron
      (Thompson) regimes. The Raman regime is shown to be preferable for the coherent
      spontaneous second harmonic generation by ultrarelativistic electron beams. Raman
      excitations in a noncollinear FEL, e.g., in an FEL without inversion, are favored
      by the noncollinear geometry of the electron and the laser beams, and by the
      relativity of the beam electrons.

PMID- 17025757
TI  - Electromagnetic forces on the dielectric layers of the planar optical Bragg
      acceleration structure.
AB  - Optical Bragg acceleration structures are waveguides with a vacuum core and
      dielectric layers as a cladding, designed to guide laser light at the speed-of
      light TM mode and accelerate charged particles. In this study, we analyze the
      electromagnetic forces exerted on the dielectric layers of a planar structure by
      both the guided laser light and the wake-field of moving charges. The
      distribution of the volume force densities, as well as the surface force
      densities, in the interfaces between the layers as a result of the laser
      propagation is given, and analytic scaling laws for the maximal values are
      obtained. Separation of the wake-field into the structure's eigenmodes is
      essential in order to determine the different contributions of the wake-field to
      the total impulse that acts on the structure. It is shown that the impact of the
      wake-field on the structure results almost entirely from the fundamental TM mode.
      While the total force on the dielectric layers may be significantly stronger than
      the gravitational force, we show that for typical structures, the pressures that
      develop are orders of magnitude below the damage threshold.

PMID- 17025758
TI  - Delay times and detector times for optical pulses traversing plasmas and negative
      refractive media.
AB  - We show that arrival times for electromagnetic pulses measured through the rate
      of absorption in an ideal impedance matched detector are equivalent to the
      arrival times using the average flow of optical energy as proposed by Peatross
      [Phys. Rev. Lett. 84, 2370 (2000)]. We then investigate the transport of optical
      pulses through dispersive media with negative dielectric permittivity and
      negative refractive index choosing the geometry such that no resonant effects
      come into play. For evanescent waves, the definitions of the group delay, and the
      reshaping delay get interchanged in comparison to propagating waves. The total
      delay times for the evanescent waves can be negative in an infinite plasma medium
      even for broadband pulses. The total delay time is, however, positive for
      broadband pulses in the presence of an interface when the radiation is detected
      outside the plasma. We find evidence of the Hartman effect for pulses when the
      distance traversed in the plasma is much smaller than the free space pulse
      length. We also show that for a negative refractive index medium (NRM) with
      epsilon(omega)=mu(omega) the reshaping delay for propagating waves is identically
      zero. The total delay time in NRM is otherwise dominated by the reshaping delay
      time, and for broadband pulses in NRM the total delay time is subluminal.

PMID- 17025759
TI  - Statics and dynamics of an inhomogeneously nonlinear lattice.
AB  - We introduce an inhomogeneously nonlinear Schrodinger lattice, featuring a
      defocusing segment, a focusing segment and a transitional interface between the
      two. We illustrate that such inhomogeneous settings present vastly different
      dynamical behavior in the vicinity of the interface than the one expected in
      their homogeneous counterparts. We analyze the relevant stationary states, as
      well as their stability, by means of perturbation theory and linear stability
      analysis. We find good agreement with the numerical findings in the vicinity of
      the anticontinuum limit. For larger values of the coupling, we follow the
      relevant branches numerically and show that they terminate at values of the
      coupling strength which are larger for more extended solutions. The dynamical
      development of relevant instabilities is also monitored in the case of unstable
      solutions.

PMID- 17025760
TI  - Optical properties and diffraction effects in opal photonic crystals.
AB  - Optical properties of fcc opals oriented along the [111] direction are calculated
      by means of a scattering-matrix approach based on approximating each sphere with
      cylindrical slices. The use of a plane-wave basis in each layer allows
      distinguishing zero-order reflection and transmission from higher-order
      (diffraction) spectra. Optical spectra at large values of the angle of incidence
      indicate the presence of diffraction effects and of polarization mixing along the
      LW orientation. Reflectance and transmittance in the high-energy region show a
      rich spectral dependence and compare reasonably well with recent experimental
      observations on polystyrene opals. Diffraction spectra as a function of the
      number of layers display an oscillatory behavior, pointing to the existence of a
      Pendellosung phenomenon, related to the exchange of energy between two
      propagating modes in the investigated three-dimensional photonic crystal. This
      phenomenon could be observed in transmittance experiments on high-quality opals
      with controlled thickness.

PMID- 17025761
TI  - Characterization of a planar artificial magnetic metamaterial surface.
AB  - We explore the electromagnetic characterization of a planar artificial magnetic
      metamaterial. Because the composite structure is two- rather than three
      dimensional, it does not form a medium with assignable bulk properties, such as
      the electric permittivity and magnetic permeability. However, we find that it is
      possible to characterize the expected bulk response of a structure composed of
      repeated layers of metamaterial planes, from a reflectance measurement of a
      single metamaterial surface made at an oblique angle. We present an analytical
      theory that relates the reflectance of a single plane to the expected bulk
      permeability and permeability of the composite, as well as supporting experiments
      and numerical simulations. Our results show that the recent use of reflectance
      measurements to characterize planar split ring resonator samples can reveal the
      presence of circulating currents in a sample--the precursor to artificial
      magnetism--but are insufficient to provide quantitative results unless the
      symmetry of the underlying metamaterial elements is carefully specified.

PMID- 17025762
TI  - Accessing quadratic nonlinearities of metals through metallodielectric photonic
      band-gap structures.
AB  - We study second harmonic generation in a metallodielectric photonic-band-gap
      structure made of alternating layers of silver and a generic, dispersive, linear,
      dielectric material. We find that under ideal conditions the conversion
      efficiency can be more than two orders of magnitude greater than the maximum
      conversion efficiency achievable in a single layer of silver. We interpret this
      enhancement in terms of the simultaneous availability of phase matching
      conditions over the structure and good field penetration into the metal layers.
      We also give a realistic example of a nine-period, Si3/N4Ag stack, where the
      backward conversion efficiency is enhanced by a factor of 50 compared to a single
      layer of silver.

PMID- 17025763
TI  - Influence of correlations between scatterers on the attenuation of the coherent
      wave in a random medium.
AB  - Experimental measurements of the coherent wave transmission for ultrasonic waves
      propagating in water through a random set of scatterers (metallic rods) are
      presented. Though the densities are moderate (6% and 14%) the experimental
      results show that the mean-free path deviates from the classical first-order
      approximation due to the existence of correlations between scatterers.
      Theoretical results for the mean free path obtained from different approaches are
      compared to the experimental measurements. The best agreement is obtained with
      the second-order diagrammatic expansion of the self-energy.

PMID- 17025764
TI  - Discrete solitons and vortices in the two-dimensional Salerno model with
      competing nonlinearities.
AB  - An anisotropic lattice model in two spatial dimensions, with on-site and
      intersite cubic nonlinearities (the Salerno model), is introduced, with emphasis
      on the case in which the intersite nonlinearity is self-defocusing, competing
      with on-site self-focusing. The model applies, for example, to a dipolar Bose
      Einstein condensate trapped in a deep two-dimensional (2D) optical lattice.
      Soliton families of two kinds are found in the model: ordinary ones and cuspons,
      with peakons at the border between them. Stability borders for the ordinary
      solitons are found, while all cuspons (and peakons) are stable. The Vakhitov
      Kolokolov criterion does not apply to cuspons, but for the ordinary solitons it
      correctly identifies the stability limits. In direct simulations, unstable
      solitons evolve into localized pulsons. Varying the anisotropy parameter, we
      trace a transition between the solitons in 1D and 2D versions of the model. In
      the isotropic model, we also construct discrete vortices of two types, on-site
      and intersite centered (vortex crosses and squares, respectively), and identify
      their stability regions. In simulations, unstable vortices in the noncompeting
      model transform into regular solitons, while in the model with the competing
      nonlinearities they evolve into localized vortical pulsons, which maintain their
      topological character. Bound states of regular solitons and vortices are
      constructed too, and their stability is identified.

PMID- 17025765
TI  - Quasibreathers as a generalization of the concept of discrete breathers.
AB  - The majority of dynamical objects, which demonstrate energy localization in
      nonlinear lattices, represent quasibreathers rather than strictly time-periodic
      discrete breathers since, as a rule, there exist certain deviations in
      vibrational frequencies of the individual particles exceeding the possible
      numerical errors. We illustrate this idea with the James breathers in the K2-K3
      K4 chain and with quasibreathers in the K4 chain. For the latter case, a rigorous
      investigation of existence and stability of the breathers and quasibreathers is
      presented. In particular, it is proved that they are stable up to a certain
      strength of the intersite part of the potential with respect to its on-site part.
      We conjecture that quasibreathers play a fundamental role in the problem of
      energy localization in more realistic nonlinear lattices, as well. The difference
      between breathers and quasibreathers can be characterized by the mean square
      deviation of the frequencies of individual particles.

PMID- 17025766
TI  - Spatial Kerr soliton collisions at arbitrary angles.
AB  - The theory of spatial Kerr solitons is extended to colliding beams that are
      neither almost-exactly copropagating nor almost-exactly counterpropagating. Our
      new Helmholtz formalism yields results that are consistent with the inherent
      symmetry of the collision process and that are not predicted by existing paraxial
      descriptions. Full numerical and approximate analytical results are presented.
      These show excellent agreement. In particular, Kerr solitons are found to be
      remarkably robust under nonparaxial collisions.

PMID- 17025767
TI  - Feshbach resonance management of Bose-Einstein condensates in optical lattices.
AB  - We analyze gap solitons in trapped Bose-Einstein condensates (BECs) in optical
      lattice potentials under Feshbach resonance management. Starting with an averaged
      Gross-Pitaevsky equation with a periodic potential, we employ an envelope-wave
      approximation to derive coupled-mode equations describing the slow BEC dynamics
      in the first spectral gap of the optical lattice. We construct exact analytical
      formulas describing gap soliton solutions and examine their spectral stability
      using the Chebyshev interpolation method. We show that these gap solitons are
      unstable far from the threshold of local bifurcation and that the instability
      results in the distortion of their shape. We also predict the threshold of the
      power of gap solitons near the local bifurcation limit.

PMID- 17025768
TI  - Generalized power-spectrum Larmor formula for an extended charged particle
      embedded in a harmonic oscillator.
AB  - The nonrelativistic Larmor radiation formula, giving the power radiated by an
      accelerated charged point particle, is generalized for a spatially extended
      particle in the context of the classical charged harmonic oscillator. The
      particle is modeled as a spherically symmetric rigid charge distribution that
      possesses both translational and spinning degrees of freedom. The power spectrum
      obtained exhibits a structure that depends on the form factor of the particle,
      but reduces, in the limit of an infinitesimally small particle and for the charge
      distributions considered, to Larmor's familiar result. It is found that for
      finite-duration small-enough accelerations as well as perpetual uniform
      accelerations the power spectrum of the spatially extended particle reduces to
      that of a point particle. It is also found that when the acceleration is violent
      or the size parameter of the particle is very large compared to the wavelength of
      the emitted radiation the power spectrum is highly suppressed. Possible
      applications are discussed.

PMID- 17025769
TI  - Subwavelength fractional Talbot effect in layered heterostructures of composite
      metamaterials.
AB  - We demonstrate that under certain conditions, fractional Talbot revivals can
      occur in heterostructures of composite metamaterials, such as multilayer positive
      and negative-index media, metallodielectric stacks, and one-dimensional
      dielectric photonic crystals. Without recourse to the paraxial approximation, we
      also obtain Talbot images for the feature sizes of transverse patterns smaller
      than the illumination wavelength. A general expression for the Talbot distance in
      such structures is derived, and the conditions favorable for observing Talbot
      effects in layered heterostructures are discussed.

PMID- 17025770
TI  - Soliton dynamics and interactions in dynamically photoinduced lattices.
AB  - The dynamics of a spatial soliton pulse and interactions under the presence of a
      linear periodic wave (PW), which dynamically induces a photonic lattice, is
      investigated. It is shown that appropriate selections of the characteristic
      parameters of the PW result in different soliton propagation and interaction
      scenarios, suggesting a reconfigurable soliton control mechanism. The
      quasiparticle perturbation method is utilized for providing a dynamical system,
      governing the soliton parameters evolution, for single- and two-soliton
      propagation under generic conditions for the PW. Results of the perturbation
      method are shown in good agreement with direct numerical simulations.

PMID- 17025771
TI  - Modulational instability criteria for coupled nonlinear transmission lines with
      dispersive elements.
AB  - We investigate the modulational instability of Stokes wave solutions on a system
      of coupled nonlinear electrical transmission lines with dispersive elements. In
      the continuum limit, and in suitable scaled coordinates, the voltage on the
      system is described by the two-dimensional coupled nonlinear Schrodinger
      equations. The set of coupled nonlinear Schrodinger equations obtained is
      analyzed via a perturbation approach. No assumption is made on the signs of the
      relevant coefficients such as the coefficients of nonlinearity and the coupling
      coefficients. A set of explicit criteria of modulational stability and
      modulational instability is derived and analyzed. It is numerically shown that
      the effect of the dispersive elements in the line is to decrease the instability
      region and the instability growth rate.

PMID- 17025772
TI  - Direct calculation of thermal emission for three-dimensionally periodic photonic
      crystal slabs.
AB  - We perform direct thermal emission calculations for three-dimensionally periodic
      photonic crystal slabs using stochastic electrodynamics following the Langevin
      approach, implemented via a finite-difference time-domain algorithm. We
      demonstrate that emissivity and absorptivity are equal, by showing that such
      photonic crystal systems emit as much radiation as they absorb, for every
      frequency, up to statistical fluctuations. We also study the effect of surface
      termination on absorption and emission spectra from these systems.

PMID- 17025773
TI  - Calculation of optical-waveguide grating characteristics using Green's functions
      and Dyson's equation.
AB  - We present a method for calculating the transmission spectra, dispersion, and
      time delay characteristics of optical-waveguide gratings based on Green's
      functions and Dyson's equation. Starting from the wave equation for transverse
      electric modes we show that the method can solve exactly both the problems of
      coupling of counterpropagating waves (Bragg gratings) and co-propagating waves
      (long-period gratings). In both cases the method applies for gratings with
      arbitrary dielectric modulation, including all kinds of chirp and apodization and
      possibly also imperfections in the dielectric modulation profile of the grating.
      Numerically, the method scales as O(N) where N is the number of points used to
      discretize the grating along the propagation axis. We consider optical fiber
      gratings although the method applies to all one-dimensional (1D) optical
      waveguide gratings including high-index contrast gratings and 1D photonic
      crystals.

PMID- 17025774
TI  - Widely tunable soliton frequency shifting of few-cycle laser pulses.
AB  - Photonic-crystal fibers are employed to demonstrate widely tunable frequency down
      conversion of unamplified 6-fs Ti:sapphire laser pulses through the soliton self
      frequency shift induced by the Raman effect. Wavelength shifts as large as 500 nm
      are achieved for input few-cycle pulses with broadband spectra centered at
      approximately 820 nm. The central wavelength of the redshifted output of a
      photonic-crystal fiber is smoothly tuned from the low-frequency edge in the
      spectrum of the 6-fs Ti:sapphire laser pulse up to 1.35 microm by varying the
      input energy in the fundamental mode of the fiber.

PMID- 17025775
TI  - Correlation transfer equation for ultrasound-modulated multiply scattered light.
AB  - In this paper, we develop a temporal correlation transfer equation (CTE) for
      ultrasound-modulated multiply scattered light. The equation can be used to obtain
      the time-varying specific intensity of light produced by a nonuniform ultrasound
      field in optically scattering media that have a heterogeneous distribution of
      optical parameters. We also develop a Monte Carlo algorithm that can provide the
      spatial distribution of the optical power spectrum in optically scattering media
      with focused ultrasound fields, and heterogeneous distributions of optically
      scattering and absorbing objects. Derivation of the CTE is based on the ladder
      diagram approximation of the Bethe-Salpeter equation that assumes moderate
      ultrasound pressures. We expect the CTE to be applicable to a wide spectrum of
      conditions in the ultrasound-modulated optical tomography of soft biological
      tissues.

PMID- 17025776
TI  - Sonar pulse wave form optimization in cluttered environments.
AB  - A theory of active sonar (or radar) pulse wave form design, for optimal target
      detection in cluttered environments, is presented. The received target signal is
      maximized via a cost function L that incorporates both the signal-to-noise ratio
      and a generalization of the Heisenberg uncertainty principle, which is used to
      balance bandwidth (or range resolution) against signal gain. The optimal pulse
      wave form is the ground state solution to a one-dimensional Schrodinger-type
      equation in frequency space, with an effective potential energy that tends to
      concentrate pulse energy in frequency bands where the target reflectivity
      dominates the clutter reflectivity.

PMID- 17025777
TI  - Microwave whirlpools in a rectangular waveguide cavity with a thin ferrite disk.
AB  - We study a three-dimensional system of a rectangular waveguide resonator with an
      inserted thin ferrite disk. The interplay of reflection and transmission at the
      disk interfaces together with a material gyrotropy effect, gives rise to a rich
      variety of wave phenomena. We analyze the wave propagation based on full Maxwell
      equation numerical solutions of the problem. We show that the power-flow lines of
      the microwave-cavity field interacting with a ferrite disk, in the proximity of
      its ferromagnetic resonance, form whirlpool-like electromagnetic vortices. Such
      vortices are characterized by the dynamical symmetry breaking. The role of ohmic
      losses in waveguide walls and dielectric and magnetic losses in a disk are the
      subjects of our investigations.

PMID- 17025778
TI  - Full-wave simulations of electromagnetic cloaking structures.
AB  - Pendry et al. have reported electromagnetically anisotropic and inhomogeneous
      shells that, in theory, completely shield an interior structure of arbitrary size
      from electromagnetic fields without perturbing the external fields. Neither the
      coordinate transformation-based analytical formulation nor the supporting ray
      tracing simulation indicate how material perturbations and full-wave effects
      might affect the solution. We report fully electromagnetic simulations of the
      cylindrical version of this cloaking structure using ideal and nonideal (but
      physically realizable) electromagnetic parameters that show that the low
      reflection and power-flow bending properties of the electromagnetic cloaking
      structure are not especially sensitive to modest permittivity and permeability
      variations. The cloaking performance degrades smoothly with increasing loss, and
      effective low-reflection shielding can be achieved with a cylindrical shell
      composed of an eight- (homogeneous) layer approximation of the ideal continuous
      medium. An imperfect but simpler version of the cloaking material is derived and
      is shown to reproduce the ray bending of the ideal material in a manner that may
      be easier to experimentally realize.

PMID- 17025779
TI  - Perturbative analysis of generally nonlocal spatial optical solitons.
AB  - In analogy to a perturbed harmonic oscillator, we calculate the fundamental and
      some other higher order soliton solutions of the nonlocal nonlinear Schodinger
      equation (NNLSE) in the second approximation in the generally nonlocal case.
      Comparing with numerical simulations we show that soliton solutions in the second
      approximation can describe the generally nonlocal soliton states of the NNLSE
      more exactly than that in the zeroth approximation. We show that for the nonlocal
      case of an exponential-decay type nonlocal response the Gaussian-function-like
      soliton solutions cannot describe the nonlocal soliton states exactly even in the
      strongly nonlocal case. The properties of such nonlocal solitons are
      investigated. In the strongly nonlocal limit, the soliton's power and phase
      constant are both in inverse proportion to the fourth power of its beam width for
      the nonlocal case of a Gaussian function type nonlocal response, and are both in
      inverse proportion to the third power of its beam width for the nonlocal case of
      an exponential-decay type nonlocal response.

PMID- 17025780
TI  - Worm algorithm and diagrammatic Monte Carlo: a new approach to continuous-space
      path integral Monte Carlo simulations.
AB  - A detailed description is provided of a new worm algorithm, enabling the accurate
      computation of thermodynamic properties of quantum many-body systems in
      continuous space, at finite temperature. The algorithm is formulated within the
      general path integral Monte Carlo (PIMC) scheme, but also allows one to perform
      quantum simulations in the grand canonical ensemble, as well as to compute off
      diagonal imaginary-time correlation functions, such as the Matsubara Green
      function, simultaneously with diagonal observables. Another important innovation
      consists of the expansion of the attractive part of the pairwise potential energy
      into elementary (diagrammatic) contributions, which are then statistically
      sampled. This affords a complete microscopic account of the long-range part of
      the potential energy, while keeping the computational complexity of all updates
      independent of the size of the simulated system. The computational scheme allows
      for efficient calculations of the superfluid fraction and off-diagonal
      correlations in space-time, for system sizes which are orders of magnitude larger
      than those accessible to conventional PIMC. We present illustrative results for
      the superfluid transition in bulk liquid 4He in two and three dimensions, as well
      as the calculation of the chemical potential of hcp 4He.

PMID- 17025781
TI  - Free-energy calculations with multiple Gaussian modified ensembles.
AB  - We present a Monte Carlo algorithm, which samples free energies of complex
      systems. Less probable configurations are populated with the help of a multitude
      of additional Gaussian weights and parallel tempering is used for efficient Monte
      Carlo moves within phase space. The algorithm is easily parallelized and can be
      applied to a wide class of problems. We discuss algorithmic performance for the
      case of low-temperature phase separation in two-dimensional and three-dimensional
      Ising models, where we determine the magnetic interface tension. Multiple
      Gaussian modified ensemble simulations, unlike multicanonical ensemble
      simulations do not require a priori knowledge of the free energy and are of
      similar efficiency as multicanonical ensemble and Wang-Landau simulations.

PMID- 17025783
TI  - Lattice Boltzmann schemes for the nonlinear Schrodinger equation.
AB  - The lattice Boltzmann (LB) method is applied to solve the time-dependent
      nonlinear Schrodinger (NLS) equation. Through approximating the reaction term at
      different orders of accuracy, three diffusion-reaction LB schemes are constructed
      for the cubic NLS equation. A LB initial condition is proposed to include the
      first-order nonequilibrium distribution function. These LB schemes are used to
      solve the one-soliton propagation and the homoclinic orbit problems. Detailed
      simulation results confirm that the high-order reaction term and the LB initial
      condition are effective in reducing the truncation errors. Compared with the
      Crank-Nicolson finite difference scheme, the LB scheme is found to give at least
      comparable and generally more accurate approximation for the cubic NLS equation.

PMID- 17025782
TI  - Extrapolated gradientlike algorithms for molecular dynamics and celestial
      mechanics simulations.
AB  - A class of symplectic algorithms is introduced to integrate the equations of
      motion in many-body systems. The algorithms are derived on the basis of an
      advanced gradientlike decomposition approach. Its main advantage over the
      standard gradient scheme is the avoidance of time-consuming evaluations of force
      gradients by force extrapolation without any loss of precision. As a result, the
      efficiency of the integration improves significantly. The algorithms obtained are
      analyzed and optimized using an error-function theory. The best among them are
      tested in actual molecular dynamics and celestial mechanics simulations for
      comparison with well-known nongradient and gradient algorithms such as the
      Stormer-Verlet, Runge-Kutta, Cowell-Numerov, Forest-Ruth, Suzuki-Chin, and
      others. It is demonstrated that for moderate and high accuracy, the extrapolated
      algorithms should be considered as the most efficient for the integration of
      motion in molecular dynamics simulations.

PMID- 17025784
TI  - Improving the accuracy of Weyl-Heisenberg wavelet and symmetrized Gaussian
      representations using customized phase-space-region operators.
AB  - A particular basis set method developed by one of the authors, involving
      maximally localized orthogonal Weyl-Heisenberg wavelets (or "weylets") and a
      phase space truncation scheme, has been successfully applied to exact quantum
      calculations for many degrees of freedom (DOF's) [B. Poirier and A. Salam, J.
      Chem. Phys. 121, 1740 (2004)]. However, limitations in accuracy arise in the many
      DOF case, owing to memory limits on conventional computers. This paper addresses
      this accuracy limitation by introducing phase space region operators (PSRO's)
      that customize individual weylet basis functions for the problem of interest. The
      construction of the PSRO's is straightforward, and does not require a priori
      knowledge of the desired eigenstates. The PSRO, when applied to weylets, as well
      as to simple phase space Gaussian basis functions, exhibits remarkable
      improvements in accuracy, reducing computed eigenvalue errors by orders of
      magnitude. The method is applied to various model systems at varying DOF's.

PMID- 17025785
TI  - Consensus in a heterogeneous influence network.
AB  - We consider a dynamical network model in which a number of agents all move on the
      plane with the same constant absolute velocity. At each time step, each agent's
      direction is updated as the average of its direction plus the directions of other
      agents who can influence it. The influencing capability of each agent is
      represented by its influencing radius, which is randomly chosen according to a
      power-law distribution with a scaling exponent between 2 and infinity. As the
      value of the scaling exponent decreases, the radius distribution becomes more
      heterogeneous and the network becomes much easier to achieve direction consensus
      among agents due to the leading roles played by a few hub agents. Furthermore,
      almost all agents will finally move in the same desired direction in a strong
      heterogeneous influence network, if and only if a small fraction of hub agents
      can be controlled to move in the desired direction. These results also reflect
      the "robust yet fragile" feature of a heterogeneous influence network.

PMID- 17025786
TI  - Nonequilibrium properties of the one-dimensional hard-point gas system.
AB  - We discuss the stability properties of a one-dimensional hard-point gas. We study
      the decay of the Loschmidt echo which describes the stability of the motion under
      system perturbations. We show a universal behavior in the echo decay which is
      intimately connected to the linear dynamical instability of the motion. In
      particular, in spite of such a weak instability, the asymptotic decay follows a
      simple exponential law.

PMID- 17025787
TI  - Richtmyer-Meshkov flow in elastic solids.
AB  - Richtmyer-Meshkov flow is studied by means of an analytical model which describes
      the asymptotic oscillations of a corrugated interface between two perfectly
      elastic solids after the interaction with a shock wave. The model shows that the
      flow stability is due to the restoring effect of the elastic force. It provides a
      simple approximate but still very accurate formula for the oscillation period. It
      also shows that as it is observed in numerical simulations, the amplitude
      oscillates around a mean value equal to the post-shock amplitude, and that this
      is a consequence of the stress free conditions of the material immediately after
      the shock interaction. Extensive numerical simulations are presented to validate
      the model results.

PMID- 17025788
TI  - Multiplicity of steady states in cylindrical Rayleigh-Benard convection.
AB  - Three-dimensional steady Rayleigh-Benard convection in a vertical cylinder is
      investigated by numerical simulation and bifurcation analysis. The complex
      pattern formation beyond the onset of the convection is presented by a
      bifurcation diagram. The coexistence of multiple stable states is observed near
      the threshold of the first bifurcation and two group symmetries are summarized
      for the corresponding primary branches. The first stable target pattern
      originates through a subcritical bifurcation. A multiplicity of flow states for
      the Rayleigh number of 14200 is validated numerically in comparison with the
      experiment, and a four-spoke pattern is observed.

PMID- 17025789
TI  - Second-order lattice Fokker-Planck algorithm from the trapezoidal rule.
AB  - The well-established procedure of deriving lattice Boltzmann schemes using the
      trapezoidal rule for time integration is generalized to the recently introduced
      lattice Fokker-Planck method.

PMID- 17025790
TI  - Behavior of heuristics on large and hard satisfiability problems.
AB  - We study the behavior of a heuristic for solving random satisfiability problems
      by stochastic local search near the satisfiability threshold. The heuristic for
      average satisfiability (ASAT), is similar to the Focused Metropolis Search
      heuristic, and shares the property of being focused, i.e., only variables in
      unsatisfied clauses are updated in each step. It is significantly simpler than
      the benchmark WALKSAT heuristic. We show that ASAT solves instances as large as
      N=10(6) in linear time, on average, up to a ratio of 4.21 clauses per variable in
      random three-satisfiability. For K higher than 3, ASAT appears to solve instances
      of K -satisfiability up to the Montanari-Ricci-Tersenghi-Parisi full replica
      symmetry breaking (FSRB) threshold denoted alpha(s)(K) in linear time.

PMID- 17025791
TI  - Stabilization of the lattice Boltzmann method using the Ehrenfests' coarse
      graining idea.
AB  - The lattice Boltzmann method (LBM) and its variants have emerged as promising,
      computationally efficient and increasingly popular numerical methods for modeling
      complex fluid flow. However, it is acknowledged that the method can demonstrate
      numerical instabilities, e.g., in the vicinity of shocks. We propose a simple
      technique to stabilize the LBM by monitoring the difference between microscopic
      and macroscopic entropy. Populations are returned to their equilibrium states if
      a threshold value is exceeded. We coin the name Ehrenfests' steps for this
      procedure in homage to the vehicle that we use to introduce the procedure,
      namely, the Ehrenfests' coarse-graining idea.

PMID- 17025793
TI  - Transfer of nonclassical properties from a microscopic superposition to
      macroscopic thermal states in the high temperature limit.
AB  - We present several examples where prominent quantum properties are transferred
      from a microscopic superposition to thermal states at high temperatures. Our work
      is motivated by an analogy of Schrodinger's cat paradox, where the state
      corresponding to the virtual cat is a mixed thermal state with a large average
      photon number. Remarkably, quantum entanglement can be produced between thermal
      states with nearly the maximum Bell-inequality violation even when the
      temperatures of both modes approach infinity.

PMID- 17025792
TI  - Absorbing boundary conditions for nonlinear Schrodinger equations.
AB  - A local time-splitting method (LTSM) is developed to design absorbing boundary
      conditions for numerical solutions of time-dependent nonlinear Schrodinger
      equations associated with open boundaries. These boundary conditions are
      significant for numerical simulations of propagations of nonlinear waves in
      physical applications, such as nonlinear fiber optics and Bose-Einstein
      condensations. Numerical examples are implemented to demonstrate the attractive
      features of using the LTSM.

PMID- 17025794
TI  - Anyon-fermion mapping and applications to ultracold gases in tight waveguides.
AB  - The Fermi-Bose mapping method for one-dimensional Bose and Fermi gases with zero
      range interactions is generalized to an anyon-fermion mapping and applied to
      exact solution of several models of ultracold gases with anyonic exchange
      symmetry in tight waveguides: anyonic Calogero-Sutherland model, anyons with
      point hard-core interaction (anyonic Tonks-Girardeau gas), and spin-aligned anyon
      gas with infinite zero-range odd-wave attractions (attractive anyonic Tonks
      Girardeau, or AATG, gas). It is proved that for even N>or=4 there are states of
      the AATG gas on a ring, with anyonic phase slips which are odd integral multiples
      of pi/(N-1), of energy lower than that of the corresponding fermionic ground
      state. A generalization to a spinor Fermi gas state with anyonic symmetry under
      purely spatial exchange enables energy lowering by the same mechanism.

PMID- 17025795
TI  - Higher harmonics in vacuum from nonlinear QED effects without low-mass
      intermediate particles.
AB  - We show that in the presence of a slowly rotating strong transverse magnetic
      field there is an infinite spectrum of harmonic wave functions An due to the
      first order QED correction (in alpha2) given by the Euler-Heisenberg Lagrangian.
      The frequency shifts are integer multiples +/- omega(0)n of the magnetic field
      angular frequency rotation omega(0)=2pinu(m), and the several modes n are coupled
      to the nearest harmonics n+/-1. This is a new effect due to QED vacuum
      fluctuations, not exploited before, that can explain, both qualitatively and
      quantitatively, the recent experimental results of the PVLAS collaboration
      without the need of a low-mass intermediate particle, hence may dismiss the
      recent claim of the discovery of the axion.

PMID- 17025796
TI  - Two-species fermion mixtures with population imbalance.
AB  - We analyze the phase diagram of uniform superfluidity for two-species fermion
      mixtures from the Bardeen-Cooper-Schrieffer to Bose-Einstein condensation (BEC)
      limit as a function of the scattering parameter and population imbalance. We find
      at zero temperature that the phase diagram of population imbalance versus
      scattering parameter is asymmetric for unequal masses, having a larger stability
      region for uniform superfluidity when the lighter fermions are in excess. In
      addition, we find topological quantum phase transitions associated with the
      disappearance or appearance of momentum space regions of zero quasiparticle
      energies. Lastly, near the critical temperature, we derive the Ginzburg-Landau
      equation and show that it describes a dilute mixture of composite bosons and
      unpaired fermions in the BEC limit.

PMID- 17025797
TI  - Pair correlations of an expanding superfluid Fermi gas.
AB  - The pair correlation function of an expanding gas is investigated with an
      emphasis on the BEC-BCS crossover of a superfluid Fermi gas at zero temperature.
      At unitarity quantum Monte Carlo simulations reveal the occurrence of a sizable
      bunching effect due to interactions in the spin up-down channel which, at short
      distances, is larger than that exhibited by thermal bosons in the Hanbury-Brown
      Twiss effect. We propose a local equilibrium ansatz for the pair correlation
      function which we predict will remain isotropic during the expansion even if the
      trapping potential is anisotropic, in contrast with the behavior of the density.
      The isotropy of the pair correlation function is an experimentally accessible
      signature, which makes a clear distinction with respect to the case of
      noninteracting gases and can be understood as a consequence of the violation of
      scaling.

PMID- 17025798
TI  - Single spin measurement using cellular automata techniques.
AB  - We analyze a conceptual approach to single-spin measurement. The method uses
      techniques from the theory of quantum cellular automata to correlate a large
      number of ancillary spins to the one to be measured. It has the distinct
      advantage of being efficient: under ideal conditions, it requires the application
      of only O((3)square root N)) steps (each requiring a constant number of rf
      pulses) to create a system of N correlated spins. Numerical simulations suggest
      that it is also, to a certain extent, robust against pulse errors, and imperfect
      initial polarization of the ancilla spin system.

PMID- 17025799
TI  - Entanglement of superpositions.
AB  - Given a bipartite quantum state (in arbitrary dimension) and a decomposition of
      it as a superposition of two others, we find bounds on the entanglement of the
      superposition state in terms of the entanglement of the states being superposed.
      In the case that the two states being superposed are biorthogonal, the answer is
      simple, and, for example, the entanglement of the superposition cannot be more
      than one ebit more than the average of the entanglement of the two states being
      superposed. However, for more general states, the situation is very different.

PMID- 17025800
TI  - Incomplete equilibrium in long-range interacting systems.
AB  - We use Hamiltonian dynamics to discuss the statistical mechanics of long-lasting
      quasistationary states particularly relevant for long-range interacting systems.
      Despite the presence of an anomalous single-particle velocity distribution, we
      find that the central limit theorem implies the Boltzmann expression in Gibbs'
      Gamma space. We identify the nonequilibrium submanifold of Gamma space
      characterizing the anomalous behavior and show that by restricting the Boltzmann
      Gibbs approach to this submanifold we obtain the statistical mechanics of the
      quasistationary states.

PMID- 17025801
TI  - Nonanalyticities of entropy functions of finite and infinite systems.
AB  - In contrast to the canonical ensemble where thermodynamic functions are smooth
      for all finite system sizes, the microcanonical entropy can show nonanalytic
      points also for finite systems. The relation between finite and infinite system
      nonanalyticities is illustrated by means of a simple classical spinlike model
      which is exactly solvable for both finite and infinite system sizes, showing a
      phase transition in the latter case. The microcanonical entropy is found to have
      exactly one nonanalytic point in the interior of its domain. For all finite
      system sizes, this point is located at the same fixed energy value
      epsilon(c)(finite), jumping discontinuously to a different value
      epsilon(c)(infinite) in the thermodynamic limit. Remarkably, epsilon(c)(finite)
      equals the average potential energy of the infinite system at the phase
      transition point. The result indicates that care is required when trying to infer
      infinite system properties from finite system nonanalyticities.

PMID- 17025802
TI  - Theoretical near-field optical properties of branched plasmonic nanoparticle
      networks.
AB  - Extended branched networks of single-nanoparticle chains have recently been self
      assembled from colloidal suspensions. In particular, gold nanoparticle linear
      chains and complex chain networks have revealed unique signatures of plasmon
      modes in their extinction spectra. In this Letter, we investigate theoretically
      their near-field optical properties and show that a real space mapping of these
      modes can be achieved with a photon scanning tunneling microscope setup. A
      distinct subwavelength patterning of the optical near-field gives rise to well
      resolved photon scanning tunneling microscope images that can be used to identify
      the network segments able to efficiently carry optical energy.

PMID- 17025803
TI  - Implications of the measurement of the Bs(0)Bs(0) mass difference.
AB  - We analyze the significant new model independent constraints on extensions of the
      standard model (SM) that follow from the recent measurements of the Bs(0)Bs(0)
      mass difference. The time-dependent CP asymmetry in Bs-->psiphi, S(psiphi), will
      be measured with good precision in the first year of CERN Large Hadron Collider
      (LHC) data taking, which will further constrain the parameter space of many
      extensions of the SM, in particular, next-to-minimal flavor violation. The CP
      asymmetry in semileptonic Bs decay, ASL(s), is also important to constrain these
      frameworks, and could give further clues to our understanding the flavor sector
      in the LHC era. We point out a strong correlation between S(psiphi) and ASL(s) in
      a very broad class of new physics models.

PMID- 17025805
TI  - Extracting nucleon strange and anapole form factors from world data.
AB  - The complete world set of parity-violating electron scattering data up to Q2
      approximately 0.3 GeV2 is analyzed. We extract the current experimental
      determination of the strange electric and magnetic form factors of the proton, as
      well as the weak axial form factors of the proton and neutron, at Q2=0.1 GeV2.
      Within experimental uncertainties, we find that the strange form factors are
      consistent with zero, as are the anapole contributions to the axial form factors.
      Nevertheless, the correlation between the strange and anapole contributions
      suggest that there is only a small probability that these form factors all vanish
      simultaneously.

PMID- 17025806
TI  - Four-loop QCD corrections to the electroweak rho parameter.
AB  - The four-loop QCD corrections to the electroweak rho parameter arising from top
      and bottom quark loops are computed. Specifically we evaluate the missing
      "nonsinglet" piece. Using algebraic methods the amplitude is reduced to a set of
      around 50 new master integrals which are calculated with various analytical and
      numerical methods. The inclusion of the newly completed term halves the final
      value of the four-loop correction for the minimally renormalized top-quark mass.
      The predictions for the shift of the weak mixing angle and the W-boson mass are
      thus stabilized.

PMID- 17025807
TI  - Comprehensive interpretation of thermal dileptons measured at the CERN super
      proton synchrotron.
AB  - Employing thermal dilepton rates based on a medium-modified electromagnetic
      correlation function we show that recent dimuon spectra of the NA60 Collaboration
      in central In-In collisions at the CERN-SPS can be understood in terms of
      radiation from a hot and dense hadronic medium. Earlier calculated in-medium rho
      meson spectral functions provide an accurate description of the data up to dimuon
      invariant masses of about M approximately or equal to 0.9 GeV, with good
      sensitivity to the predicted rho-meson line shape, identifying baryon-induced
      modifications as the prevalent ones. A reliable evaluation of the contribution
      enables the study of further medium effects: at masses M>0.9 GeV, 4-pion type
      annihilation accounts for the experimentally observed excess (possibly augmented
      by effects of "chiral mixing"), while predictions for thermal emission from in
      medium omega and phi mesons may be tested in the future.

PMID- 17025804
TI  - Search for Theta++ pentaquarks in the exclusive reaction gammap-->K+K-p.
AB  - The reaction gammap --> pK+K- was studied at Jefferson Lab with photon energies
      from 1.8 to 3.8 GeV using a tagged photon beam. The goal was to search for a
      Theta++ pentaquark, a narrow, doubly charged baryon state having strangeness S=+1
      and isospin I=1, in the pK+ invariant mass spectrum. No statistically significant
      evidence of a Theta++ was found. Upper limits on the total and differential cross
      section for the reaction gammap --> K-Theta++ were obtained in the mass range
      from 1.5 to 2.0 GeV/c2, with an upper limit for a narrow resonance with a mass
      M(Theta++) = 1.54 GeV/c2 of about 0.15 nb, 95% C.L.. This result places a
      stringent upper limit on the Theta++ width Gamma(Theta++) <0.1 MeV/c2.

PMID- 17025808
TI  - Precision branching ratio measurement for the superallowed beta+ emitter 62Ga and
      isospin-symmetry-breaking corrections in A>or=62 nuclei.
AB  - A high-precision branching ratio measurement for the superallowed beta+ decay of
      62Ga was performed at the Isotope Separator and Accelerator radioactive ion beam
      facility. Nineteen gamma rays emitted following beta+ decay of 62Ga were
      identified, establishing the dominant superallowed branching ratio to be
      (99.861+/-0.011)%. Combined with recent half-life and Q-value measurements, this
      branching ratio yields a superallowed ft value of 3075.6+/-1.4 s for 62Ga decay.
      These results demonstrate the feasibility of high-precision superallowed
      branching ratio measurements in the A>or=62 mass region and provide the first
      stringent tests of the large isospin-symmetry-breaking effects predicted for
      these decays.

PMID- 17025809
TI  - Density functional theory in transition-metal chemistry: a self-consistent
      Hubbard U approach.
AB  - Transition-metal centers are the active sites for a broad variety of biological
      and inorganic chemical reactions. Notwithstanding this central importance,
      density-functional theory calculations based on generalized-gradient
      approximations often fail to describe energetics, multiplet structures, reaction
      barriers, and geometries around the active sites. We suggest here an alternative
      approach, derived from the Hubbard U correction to solid-state problems, that
      provides an excellent agreement with correlated-electron quantum chemistry
      calculations in test cases that range from the ground state of Fe2 and Fe2- to
      the addition elimination of molecular hydrogen on FeO+. The Hubbard U is
      determined with a novel self-consistent procedure based on a linear-response
      approach.

PMID- 17025810
TI  - Exploring relativistic many-body recoil effects in highly charged ions.
AB  - The relativistic recoil effect has been the object of experimental investigations
      using highly charged ions at the Heidelberg electron beam ion trap. Its scaling
      with the nuclear charge Z boosts its contribution to a measurable level in the
      magnetic-dipole (M1) transitions of B- and Be-like Ar ions. The isotope shifts of
      36Ar versus 40Ar have been detected with sub-ppm accuracy, and the recoil effect
      contribution was extracted from the 1s(2)2s(2)2p 2P(1/2) - 2P(3/2) transition in
      Ar13+ and the 1s(2)2s2p 3P1-3P2 transition in Ar14+. The experimental isotope
      shifts of 0.00123(6) nm (Ar13+) and 0.00120(10) nm (Ar14+) are in agreement with
      our present predictions of 0.00123(5) nm (Ar13+) and 0.00122(5) nm (Ar14+) based
      on the total relativistic recoil operator, confirming that a thorough
      understanding of correlated relativistic electron dynamics is necessary even in a
      region of intermediate nuclear charges.

PMID- 17025811
TI  - Formation of ground-state vibrational wave packets in intense ultrashort laser
      pulses.
AB  - The formation of coherent vibrational wave packets in the electronic ground state
      of neutral molecules in intense ultrashort laser pulses and their subsequent
      detection by means of recently developed pump-probe experiments are discussed.
      The wave packet formation is due to the pronounced dependence of the strong-field
      ionization rate on the internuclear distance. This leads to a deformation of the
      initial wave function due to an internuclear-distance dependent depletion. The
      phenomenon is demonstrated with a time-dependent wave packet study for molecular
      hydrogen.

PMID- 17025812
TI  - Quantum-phase resolved mapping of ground-state vibrational D2 wave packets via
      selective depletion in intense laser pulses.
AB  - Applying 7 fs pump-probe pulses (780 nm, 4 x 10(14) W/cm2) we observe electronic
      ground-state vibrational wave packets in neutral D2 with a period of T=11.101(70)
      fs by following the internuclear separation (R-)dependent ionization with a
      sensitivity of Delta<R><or=0.02 A. The absolute phase of the wave packet's motion
      provides evidence for R-dependent depletion of the ground state by nonlinear
      ionization, to be the dominant preparation mechanism. A phase shift of about pi
      found between pure ionization (D2+) and dissociation (D+ + D) channels opens a
      pathway of quantum control.

PMID- 17025813
TI  - Potential energy curves for excited states of the hydrogen-antihydrogen system.
AB  - The potential energy curves for the hydrogen-antihydrogen (HH) system in states
      with a leptonic orbital angular momentum projection Lambda=0, 1, 2, 6, and 30 are
      presented. Within the framework of the adiabatic picture, explicitly correlated
      Gaussians are used as basis functions which describe accurately the hydrogen
      antihydrogen interaction. The critical internuclear distances where the system
      transforms into positronium and protonium atoms are found. Adiabatic corrections
      to the potential energy curves are also estimated.

PMID- 17025814
TI  - Low-energy nondipole effects in molecular nitrogen valence-shell photoionization.
AB  - Observations are reported for the first time of significant nondipole effects in
      the photoionization of the outer-valence orbitals of diatomic molecules. Measured
      nondipole angular-distribution parameters for the 3sigma(g), 1pi(u), and
      2sigma(u) shells of N2 exhibit spectral variations with incident photon energies
      from thresholds to approximately 200 eV which are attributed via concomitant
      calculations to particular final-state symmetry waves arising from (E1)multiply
      sign in circle(M1,E2) radiation-matter interactions first-order in photon
      momentum. Comparisons with previously reported K-edge studies in N2 verify linear
      scaling with photon momentum, accounting in part for the significantly enhanced
      nondipole behavior observed in inner-shell ionization at correspondingly higher
      momentum values in this molecule.

PMID- 17025815
TI  - Scaling and suppression of anomalous heating in ion traps.
AB  - We measure and characterize anomalous motional heating of an atomic ion confined
      in the lowest quantum levels of a novel rf ion trap that features moveable
      electrodes. The scaling of heating with electrode proximity is measured, and when
      the electrodes are cooled from 300 to 150 K, the heating rate is suppressed by an
      order of magnitude. This provides direct evidence that anomalous motional heating
      of trapped ions stems from microscopic noisy potentials on the electrodes that
      are thermally driven. These observations are relevant to decoherence in quantum
      information processing schemes based on trapped ions and perhaps other charge
      based quantum systems.

PMID- 17025817
TI  - Photocount statistics in mesoscopic optics.
AB  - We report the first observation of the impact of mesoscopic fluctuations on the
      photocount statistics of coherent light scattered in a random medium. A Poisson
      photocount distribution of the incident light widens and gains additional
      asymmetry upon transmission through a suspension of small dielectric spheres. The
      effect is only appreciable when the average number n of photocounts becomes
      comparable or larger than the effective dimensionless conductance g of the
      sample.

PMID- 17025816
TI  - Variable time lag and backward ejection in full-dimensional analysis of strong
      field double ionization.
AB  - Ensembles of 400,000 two-electron trajectories in three space dimensions are used
      with Newtonian equations of motion to track atomic double ionization under very
      strong laser fields. We report a variable time lag between e-e collision and
      double ionization, and find that the time lag plays a key role in the emergence
      directions of the electrons. These are precursors to production of electron
      momentum distributions showing substantial new agreement with experimental data.

PMID- 17025818
TI  - Distribution of anomalous exponents of natural images.
AB  - Recent studies of correlations of intensity in databases of natural images
      revealed a remarkable property. The two point correlations are described in terms
      of power law behavior, with an exponent which seems to be robust. In the present
      Letter we consider the statistical meaning of that result. We study many
      individual images of one of the databases considered. We find that the same law
      characterizing the correlations in the whole database governs also images
      randomly chosen from that database, with one essential difference. The exponent
      characterizing each image is specific and differs from the exponent
      characterizing the whole database. The distribution of single image exponents has
      been measured and found to exhibit a rather heavy tail. The database exponent
      cannot, thus, be considered as a statistical representative of a single image
      exponent. Possible reasons for the diversity in image exponents are discussed.

PMID- 17025819
TI  - Detection of broadband terahertz waves with a laser-induced plasma in gases.
AB  - We report the experimental results and theoretical analysis of broadband
      detection of terahertz (THz) waves via electric-field-induced second-harmonic
      generation in laser-induced air plasma with ultrashort laser pulses. By
      introducing the second-harmonic component of the white light in the laser-induced
      plasma as a local oscillator, coherent detection of broadband THz waves with
      ambient air is demonstrated for the first time. Our results show that, depending
      on the probe intensity, detection of THz waves in air can be categorized as
      incoherent, hybrid, and coherent detection. Coherent detection is achieved only
      when the tunnel ionization process dominates in gases.

PMID- 17025820
TI  - Extracting multidimensional phase space topology from periodic orbits.
AB  - We establish a hierarchical ordering of periodic orbits in a strongly coupled
      multidimensional Hamiltonian system. Phase space structures can be reconstructed
      quantitatively from the knowledge of periodic orbits alone. We illustrate our
      findings for the hydrogen atom in crossed electric and magnetic fields.

PMID- 17025821
TI  - Decay of quantum correlations in atom optics billiards with chaotic and mixed
      dynamics.
AB  - We perform echo spectroscopy on ultracold atoms in atom-optics billiards to study
      their quantum dynamics. The detuning of the trapping laser is used to change the
      "perturbation", which causes a decay in the echo coherence. Two different regimes
      are observed: first, a perturbative regime in which the decay of echo coherence
      is nonmonotonic and partial revivals of coherence are observed in contrast with
      the predictions of random matrix theory. These revivals are more pronounced in
      traps with mixed dynamics as compared to traps where the dynamics is fully
      chaotic. Next, for stronger perturbations, the decay becomes monotonic and
      independent of the strength of the perturbation. In this regime no clear
      distinction can be made between chaotic traps and traps with mixed dynamics.

PMID- 17025822
TI  - Anomalous Richtmyer-Meshkov fingering in dissipative particle systems.
AB  - We study the fingering instability induced by a shock that propagates across a
      perturbed interface that separates two types of discrete particles. If collisions
      between particles conserve energy, then the relative sizes and growth rates of
      the fingers are similar to those in the analogous shock-induced fingering
      instability in fluids. However, we show that energy loss during particle
      collisions, even when very small, causes the qualitative features of the finger
      growth to be completely opposite to the fluid case. The fingers formed by light
      particles grow faster and become longer and narrower than the fingers formed by
      heavy particles. In addition, the finger composed of light particles collapses
      into an extremely compact, tortuous filament, and diffusive mixing between
      particle types at the particle scale is heavily suppressed.

PMID- 17025823
TI  - Bulk viscosity, thermoacoustic boundary layers, and adsorption near the critical
      point of xenon.
AB  - We present an improved model for the dissipation and dispersion in an acoustic
      resonator filled with xenon near its critical temperature Tc. We test the model
      with acoustic measurements in stirred xenon that have a temperature resolution of
      (T - Tc)/Tc approximately 7 x 10(-6). The model includes the frequency-dependent
      bulk viscosity calculated numerically from renormalization-group theory and it
      includes critical-point adsorption. Because the density of adsorbed xenon exceeds
      the critical density, the bulk viscosity's effect on surface dissipation is
      reduced, thereby improving the agreement between theory and experiment.

PMID- 17025824
TI  - Fundamental limit of nonscaling fixed-field alternating-gradient accelerators.
AB  - Systematic nonlinear space-charge resonances may cause substantial emittance
      growth in the nonscaling fixed-field alternating-gradient (FFAG) accelerators. To
      avoid systematic nonlinear space-charge resonances, the phase advance of each
      nonscaling FFAG cell must avoid pi/2 and pi/3. Using multiparticle numerical
      simulations, we empirically obtain a minimum tune ramp rate vs the systematic 4th
      order space-charge resonance strength. We also find that the emittance growth
      obeys a simple scaling property when the betatron tunes cross the linear half
      integer and sum resonances.

PMID- 17025825
TI  - Floppy modes and nonaffine deformations in random fiber networks.
AB  - We study the elasticity of random fiber networks. Starting from a microscopic
      picture of the nonaffine deformation fields, we calculate the macroscopic elastic
      moduli both in a scaling theory and a self-consistent effective medium theory. By
      relating nonaffinity to the low-energy excitations of the network ("floppy
      modes"), we achieve a detailed characterization of the nonaffine deformations
      present in fibrous networks.

PMID- 17025826
TI  - Novel phase transformation in ZnO nanowires under tensile loading.
AB  - We predict a previously unknown phase transformation from wurtzite to a
      graphitelike (P6(3)/mmc) hexagonal structure in [0110]-oriented ZnO nanowires
      under uniaxial tensile loading. Molecular dynamics simulations and first
      principles calculations show that this structure corresponds to a distinct
      minimum on the enthalpy surfaces of ZnO for such loading conditions. This
      transformation is reversible with a low level of hysteretic dissipation of 0.16
      J/m3 and, along with elastic stretching, endows the nanowires with the ability to
      recover pseudoelastic strains up to 15%.

PMID- 17025827
TI  - Dynamics of bimodal growth in pentacene thin films.
AB  - Previous studies have established that pentacene films deposited on silicon oxide
      consist of a substrate-induced "thin-film" phase, with the bulk phase of
      pentacene detected in thicker films only. We show that the bulk phase nucleates
      as early as the first monolayer, and continues to nucleate as film growth
      progresses, shadowing the growth of the thin-film phase. Moreover, we find that
      the transition between the "thin-film" and the bulk phase is not a continuous
      one, as observed in heteroepitaxial systems, but rather the two phases nucleate
      and grow independently.

PMID- 17025828
TI  - Freezing of a Lennard-Jones fluid: from nucleation to spinodal regime.
AB  - Using molecular dynamics, we investigate the crystal nucleation in a Lennard
      Jones fluid as a function of the degree of supercooling. At moderate
      supercooling, a nucleation picture applies, while for deeper quenches, the
      phenomenon progressively acquires a spinodal character. We show that in the
      nucleation regime, the freezing is a two-step process. The formation of the
      critical nucleus is indeed preceded by the abrupt formation of a precritical
      crystallite from a density fluctuation in the fluid. In contrast, as the degree
      of supercooling is increased, crystallization proceeds in a more continuous and
      collective fashion and becomes more spatially diffuse, indicating that the liquid
      is unstable and crystallizes by a spinodal mechanism.

PMID- 17025829
TI  - Freezing of fluids confined in a disordered nanoporous structure.
AB  - Freezing of a simple fluid in a disordered nanoporous carbon is studied using
      molecular simulations. Only partial crystallization occurs, and the confined
      phase is composed of crystalline and amorphous nanodomains. This freezing
      behavior departs strongly from that for nanopores of simple geometry. We present
      a method for analyzing the freezing in such disordered materials in terms of a
      transition in the average size and number of crystalline clusters. The results
      provide a basis for the interpretation of experiments on freezing in such
      materials, particularly 1H-NMR and scattering experiments.

PMID- 17025830
TI  - Subdiffusion and long-time anticorrelations in a stochastic single file.
AB  - The subdiffusion of a stochastic single file is interpreted as a jumping process.
      Contrary to the current continuous time random walk models, its statistics is
      characterized by finite averages of the jumping times and square displacements.
      Subdiffusion is then related to a persistent anticorrelation of the jump
      sequences. In continuous time representation, this corresponds to negative power
      law velocity autocorrelations, attributable to the restricted geometry of the
      file diffusion.

PMID- 17025831
TI  - Complete wetting of nanosculptured substrates.
AB  - Complete wetting of geometrically structured substrates by one-component fluids
      with long-ranged interactions is studied theoretically. We consider periodic
      arrays of rectangular or parabolic grooves and lattices of cylindrical or
      parabolic pits. We show that the midpoint interfacial heights within grooves and
      pits are related in the same way as for complete wedge and cone filling. For
      sufficiently deep cavities with vertical walls and small undersaturation, an
      effective planar scaling regime emerges. The scaling exponent is -1/3 in all
      cases studied, and only the amplitudes depend on the geometrical features. We
      find quantitative agreement with recent experimental data for such systems.

PMID- 17025832
TI  - Missing xy-band Fermi surface in 4d transition-metal oxide Sr2RhO4: effect of the
      octahedra rotation on the electronic structure.
AB  - Electronic structures of the 4d transition-metal oxide compound Sr2RhO4 are
      investigated by angle-resolved photoemission spectroscopy and density-functional
      electronic structure calculations. In the measured Fermi surfaces (FS) of
      Sr2RhO4, the xy-band FS sheet expected from the well-established results of the
      FS of Sr2RuO4 is missing, the volume of which should be different only by one
      additional electron for Sr2RhO4. The apparent contradiction is resolved by a
      careful analysis of the band structure where the rotation of octahedra results in
      the hybridization of e(g) and t(2g) states and thus plays a key role in the
      determination of the electronic structure near EF. The modification of the FS
      structure due to the distorted lattice is related to the charge transfer among
      the orbital states and suggested to be relevant to the metal-insulator transition
      in Ca(2-x)Sr(x)RuO4.

PMID- 17025833
TI  - E center in silicon has a donor level in the band gap.
AB  - It has been an accepted fact for more than 40 years that the E center in Si (the
      group-V impurity--vacancy pair)--one of the most studied defects in
      semiconductors--has only one energy level in the band gap: namely, the acceptor
      level at about 0.45 eV below the conduction band. We now demonstrate that it has
      a second level, situated in the lower half of the band gap at 0.27 eV above the
      valence band. The existence of this level, having a donor character, is disclosed
      by a combination of different transient-capacitance techniques and electronic
      structure calculations. The finding seriously questions some diffusion-modeling
      approaches performed in the past.

PMID- 17025834
TI  - Stripe correlations in Na(0.75)CoO2.
AB  - We present a combined high-energy x-ray diffraction and local-density
      approximation study of the sodium ordering in Na(0.75)CoO2. The obtained results
      rule out previously proposed Na-ordering models and provide strong evidence for
      the formation of sodium-density stripes in this material. The local-density
      approximation calculations prove that the sodium-density stripes lead to a
      sizable dip in the density of the Co states at the Fermi level, pointing to band
      structure effects as a driving force for the stripe formation. This indicates
      that the sodium ordering is connected to stripelike charge correlations within
      the CoO2 layers, leading to an astonishing similarity between the doped cuprates
      and the NaxCoO2 compounds.

PMID- 17025835
TI  - Spin precession and alternating spin polarization in spin-3/2 hole systems.
AB  - The spin density matrix for spin-3/2 hole systems can be decomposed into a
      sequence of multipoles which has important higher-order contributions beyond the
      ones known for electron systems [R. Winkler, Phys. Rev. B 70, 125301 (2004)]. We
      show here that the hole spin polarization and the higher-order multipoles can
      precess due to the spin-orbit coupling in the valence band, yet in the absence of
      external or effective magnetic fields. Hole spin precession is important in the
      context of spin relaxation and offers the possibility of new device applications.
      We discuss this precession in the context of recent experiments and suggest a
      related experimental setup in which hole spin precession gives rise to an
      alternating spin polarization.

PMID- 17025836
TI  - Charge transfer via a two-strand superexchange bridge in DNA.
AB  - Charge transfer in a DNA duplex chain is studied by constructing a system with
      virtual electrodes connected at the ends of each DNA strand. The system is
      described by the tight-binding model and its transport is analyzed by the
      transfer matrix method. The very weak distance dependence in a long
      (G:C)(T:A)M(G:C)3 DNA chain observed in experiment [B. Giese, Nature (London)
      412, 318 (2001)] is explained by a unistep two-strand superexchange bridge
      without the need for the multistep thermally induced hopping mechanism or the
      dephasing effect. The crossover number Mc of the (T:A) base pairs, where
      crossover between the strong and weak distance dependence occurs, reflects the
      ratio of intra- and interstrand neighboring base-base couplings.

PMID- 17025837
TI  - Microsecond resolution of quasiparticle tunneling in the single-Cooper-pair
      transistor.
AB  - We present radio-frequency measurements on a single-Cooper-pair-transistor in
      which individual quasiparticle poisoning events were observed with microsecond
      temporal resolution. Thermal activation of the quasiparticle dynamics is
      investigated, and consequently, we are able to determine energetics of the
      poisoning and unpoisoning processes. In particular, we are able to assign an
      effective quasiparticle temperature to parametrize the poisoning rate.

PMID- 17025838
TI  - Conserving many body approach to the infinite-U Anderson model.
AB  - Using a Luttinger-Ward scheme for interacting gauge particles, we present a
      conserving many body treatment of a family of fully screened infinite-U Anderson
      models that has a smooth crossover into the Fermi-liquid state, with a finite
      scattering phase shift at zero temperature and a Wilson ratio greater than 1. We
      illustrate our method, computing the temperature dependence of the
      thermodynamics, resistivity, and electron dephasing rate and discuss its future
      application to nonequilibrium quantum dots and quantum critical mixed valent
      systems.

PMID- 17025839
TI  - Probing spin-flip scattering in ballistic nanosystems.
AB  - Because spin-flip length is longer than the electron mean-free path in a metal,
      past studies of spin-flip scattering are limited to the diffusive regime. We
      propose to use a magnetic double barrier tunnel junction to study spin-flip
      scattering in the nanometer sized spacer layer near the ballistic limit. We
      extract the voltage and temperature dependence of the spin-flip conductance Gs in
      the spacer layer from magnetoresistance measurements. In addition to spin
      scattering information including the mean-free path (70 nm) and the spin-flip
      length (1.0-2.6 microm) at 4.2 K, this technique also yields information on the
      density of states and quantum well resonance in the spacer layer.

PMID- 17025840
TI  - Nonvanishing energy scales at the quantum critical point of CeCoIn5.
AB  - Heat and charge transport were used to probe the magnetic field-tuned quantum
      critical point in the heavy-fermion metal CeCoIn5. A comparison of electrical and
      thermal resistivities reveals three characteristic energy scales. A Fermi-liquid
      regime is observed below T(FL), with both transport coefficients diverging in
      parallel and T(FL) -->0 as H --> Hc, the critical field. The characteristic
      temperature of antiferromagnetic spin fluctuations, T(SF), is tuned to a minimum
      but finite value at Hc, which coincides with the end of the T-linear regime in
      the electrical resistivity. A third temperature scale, T(QP), signals the
      formation of quasiparticles, as fermions of charge e obeying the Wiedemann-Franz
      law. Unlike T(FL), it remains finite at Hc, so that the integrity of
      quasiparticles is preserved, even though the standard signature of Fermi-liquid
      theory fails.

PMID- 17025841
TI  - Electron correlations and single-particle physics in the integer quantum Hall
      effect.
AB  - The compressibility of a two-dimensional electron system with spin in a spatially
      correlated random potential and a quantizing magnetic field is investigated.
      Electron-electron interaction is treated with the Hartree-Fock method. Numerical
      results for the influences of interaction and disorder on the compressibility as
      a function of the particle density and the strength of the magnetic field are
      presented. Localization-delocalization transitions associated with a highly
      compressible region in the energy spectrum are found at half-integer filling
      factors. Coulomb blockade effects are found near integer fillings in the regions
      of low compressibility. Results are compared with recent experiments.

PMID- 17025842
TI  - Role of Pr segregation in acceptor-state formation at ZnO grain boundaries.
AB  - The role of Pr doping on double Schottky barrier formations at ZnO single grain
      boundaries was investigated by the combination of current-voltage measurements,
      atomic-resolution Z-contrast scanning transmission electron microscopy, and first
      principles calculations. Although Pr segregated to the specific atomic site along
      the boundaries, it was found not to be the direct cause of nonlinear current
      voltage properties. Instead, under appropriate annealing conditions, Pr enhances
      formations of acceptor-type native defects that are essential for the creation of
      double Schottky barriers in ZnO.

PMID- 17025843
TI  - All-electrical control of single ion spins in a semiconductor.
AB  - We propose a method for all-electrical manipulation of single ion spins
      substituted into a semiconductor. Mn ions with a bound hole in GaAs form a
      natural example. Direct electrical manipulation of the ion spin is possible,
      because electric fields manipulate the orbital wave function of the hole, and
      through the spin-orbit coupling the spin is reoriented as well. Coupling ion
      spins can be achieved using gates to control the size of the hole wave function.
      Coherent manipulation of ionic spins may find applications in high-density
      storage and in scalable coherent or quantum information processing.

PMID- 17025844
TI  - Charge and spin Hall conductivity in metallic graphene.
AB  - Graphene has an unusual low-energy band structure with four chiral bands and half
      quantized and quantized Hall effects that have recently attracted theoretical and
      experimental attention. We study the Fermi energy and disorder dependence of its
      spin Hall conductivity sigma(xy)(SH). In the metallic regime we find that vertex
      corrections enhance the intrinsic spin Hall conductivity and that skew scattering
      can lead to sigma(xy)(SH) values that exceed the quantized ones expected when the
      chemical potential is inside the spin-orbit induced energy gap. We predict that
      large spin Hall conductivities will be observable in graphene even when the spin
      orbit gap does not survive disorder.

PMID- 17025845
TI  - Increase in Tc upon reduction of doping in LixZrNCl superconductors.
AB  - We revealed a detailed phase diagram of the very lightly doped regime in Li
      intercalated superconductors, LixZrNCl, to which previous studies have never
      gained access owing to the difficulty in synthesizing single-phase samples. A
      continuous and uniform Li intercalation without any indication of phase
      separation was carefully confirmed by means of synchrotron x-ray diffraction and
      Raman scattering experiments. Upon reducing the carrier density below x=0.12, we
      found a rapid increase in the superconducting transition temperature (Tc)
      immediately followed by the superconductor-to-insulator transition (SIT). Such an
      increase in Tc on the verge of SIT seems to be difficult to explain by the
      conventional theory, but may be indicative of the charge fluctuation contribution
      to superconductivity in low-carrier-density systems.

PMID- 17025846
TI  - Three-dimensional, spin-resolved structure of magnetic vortex and antivortex
      states in patterned Co films using scanning ion microscopy with polarization
      analysis.
AB  - Scanning ion microscopy with polarization analysis is utilized for three
      dimensional spin mapping of the surface magnetization (SM) of circular Co dots
      created in situ by focused ion beam etching of 30 nm thin Co/Si(100) films. From
      3D scanning ion microscopy with polarization analysis spin maps, direct evidence
      is found for the existence of vortex-antivortex states with in-plane circular or
      hyperbolic SM components and a wide core with perpendicular SM components which
      oscillate in the outer region and become zero.

PMID- 17025847
TI  - Aggregation kinetics and the nature of phase separation in two-dimensional
      dipolar fluids.
AB  - The kinetics of aggregation in a monolayer of dipolar particles are studied using
      stochastic dynamics computer simulations. Transient concentrations of end defects
      (at low density) and Y-shaped defects (at high density) clearly exceed those at
      equilibrium. Although very large dipole moments are expected to disfavor such
      defects at equilibrium, it is found that the transient defect concentrations
      increase with increasing dipole moment. The results suggest that the conditions
      for defect-driven condensation--as proposed by Tlusty and Safran [T. Tlusty and
      S. A. Safran, Science 290, 1328 (2000)]--could be met by kinetic trapping, giving
      rise to a metastable phase transition between isotropic fluid phases.

PMID- 17025848
TI  - Field evolution of tilted vortex cores in exchange-biased ferromagnetic dots.
AB  - We developed an analytical model for the magnetization reversal via vortex
      nucleation and annihilation in double-layer ferromagnetic/antiferromagnetic
      cylindrical dots. The coupling of the ferromagnet to the antiferromagnet is
      modeled by means of an interfacial exchange field. The nonuniformity of the
      magnetization reversal mode perpendicular to the layers is explicitly included
      and results in a tilted vortex core (tilted Bloch line). The vortex core tilt
      results in an asymmetry of the nucleation and annihilation fields, which are
      calculated as a function of the dot geometry.

PMID- 17025849
TI  - Current-driven resonant excitation of magnetic vortices.
AB  - A magnetic vortex core in a ferromagnetic circular nanodot has a resonance
      frequency originating from the confinement of the vortex core. By the
      micromagnetic simulation including the spin-transfer torque, we show that the
      vortex core can be resonantly excited by an ac (spin-polarized) current through
      the dot and that the resonance frequency can be tuned by the dot shape. The
      resistance measurement under the ac current successfully detects the resonance at
      the frequency consistent with the simulation.

PMID- 17025850
TI  - A-site ordering versus electronic inhomogeneity in colossally magnetoresistive
      manganite films.
AB  - Epitaxial La(3/4)Ca(1/4)MnO3/MgO(100) (LCMO) thin film shows an unusual
      rhombohedral (R-3c) structure with a new perovskite superstructure at room
      temperature due to the CE-type ordering of La and Ca with modulation vector
      q=1/4[011]. A-site ordered film was found to be electronically homogeneous down
      to the 1 nm scale as revealed by scanning tunnelling microscopy/spectroscopy. In
      contrast, orthorhombic and A-site disordered LCMO demonstrate a mesoscopic phase
      separation far below the Curie temperature (TC). Unique La/Ca ordering
      compensates the cation mismatch stress within one supercell, a(S) approximately
      1.55 nm, and enhances the electronic homogeneity. The phase separation does not
      seem to be a unique mechanism for the colossal magnetoresistance (CMR) as very
      large CMR approximately 500% was also observed in A-site ordered films.

PMID- 17025851
TI  - Ground-state approximation for strongly interacting spin systems in arbitrary
      spatial dimension.
AB  - We introduce a variational method for the approximation of ground states of
      strongly interacting spin systems in arbitrary geometries and spatial dimensions.
      The approach is based on weighted graph states and superpositions thereof. These
      states allow for the efficient computation of all local observables (e.g.,
      energy) and include states with diverging correlation length and unbounded
      multiparticle entanglement. As a demonstration, we apply our approach to the
      Ising model on 1D, 2D, and 3D square lattices. We also present generalizations to
      higher spins and continuous-variable systems, which allows for the investigation
      of lattice field theories.

PMID- 17025852
TI  - Electrical control of a single Mn atom in a quantum dot.
AB  - We report on the reversible electrical control of the magnetic properties of a
      single Mn atom in an individual quantum dot. Our device permits us to prepare the
      dot in states with three different electric charges, 0, +1e, and -1e which result
      in dramatically different spin properties, as revealed by photoluminescence.
      Whereas in the neutral configuration the quantum dot is paramagnetic, the
      electron-doped dot spin states are spin rotationally invariant and the hole-doped
      dot spins states are quantized along the growth direction.

PMID- 17025853
TI  - Thresholds of plasma formation in silicon identified by optimizing the ablation
      laser pulse form.
AB  - Using an evolutionary algorithm combined with pulse shaping, we have identified
      that rapid plasma formation in Silicon can occur already at a fluence of about
      150 mJ/cm2 if a substantial part of the laser energy is deposited efficiently
      around 200 fs after an exciting laser pulse. Nonthermal solid-to-liquid phase
      transition leads to the increase of the deposited energy in the material. Highly
      charged ions have been observed in the mass spectrum. While the pulse
      optimization procedure allowed us to identify the plasma formation, further
      experiments where the influence of the laser pulse width on the ablation yield
      was studied and Two-Pulse-Correlation experiments provided additional proof for
      the appearance of rapid plasma formation.

PMID- 17025854
TI  - Wannier-based definition of layer polarizations in perovskite superlattices.
AB  - In insulators, the method of Marzari and Vanderbilt [Phys. Rev. B 56, 12 847
      (1997)] can be used to generate maximally localized Wannier functions whose
      centers are related to the electronic polarization. In the case of layered
      insulators, this approach can be adapted to provide a natural definition of the
      local polarization associated with each layer, based on the locations of the
      nuclear charges and one-dimensional Wannier centers comprising each layer. Here,
      we use this approach to compute and analyze layer polarizations of ferroelectric
      perovskite superlattices, including changes in layer polarizations induced by
      sublattice displacements (i.e., layer-decomposed Born effective charges) and
      local symmetry breaking at the interfaces. The method provides a powerful tool
      for analyzing the polarization-related properties of complex layered oxide
      systems.

PMID- 17025855
TI  - Effect of nonmesogenic impurities on the order of the nematic to smectic-A phase
      transition in liquid crystals.
AB  - By means of adiabatic scanning calorimetry, we have studied the effect of the
      nonmesogenic solutes cyclohexane (CH) and biphenyl (BP) on the nematic-smectic-A
      phase transition in the liquid crystal octylcyanobiphenyl (8CB). For all
      concentrations of BP studied, the transition remains second-order. For 8CB+CH,
      however, crossover from second-order to first-order is observed at a tricritical
      point of the mole fraction x of CH around 0.0460. The difference between the two
      systems and the crossover is explained in terms of a mean-field free energy
      density expression including coupling terms of x with the nematic and smectic-A
      order parameters.

PMID- 17025856
TI  - Dominant pathways in protein folding.
AB  - We present a method to investigate the kinetics of protein folding and the
      dynamics underlying the formation of secondary and tertiary structures during the
      entire reaction. By writing the solution of the Fokker-Planck equation in terms
      of a path integral, we derive a Hamilton-Jacobi variational principle from which
      we are able to compute the most probable pathway of folding. The method is
      applied to the folding of the Villin headpiece subdomain simulated using a Go
      model. An initial collapsing phase driven by the initial configuration is
      followed by a rearrangement phase, in which secondary structures are formed and
      all computed paths display strong similarities. This completely general method
      does not require the prior knowledge of any reaction coordinate and is an
      efficient tool to perform simulations of the entire folding process with
      available computers.

PMID- 17025857
TI  - RNA condensation and the wetting transition.
AB  - We present a continuum theory for the condensation of large, soluble, single
      stranded RNA molecules on attractive substrates. In the mean-field approximation,
      the theory reduces to the Cahn-de Gennes description of wetting fluids and offers
      a natural explanation for the development of a sharply defined density profile
      following a prewetting surface phase transition. This mapping onto the wetting
      problem can break down because of a capillary instability where the adsorbed film
      decomposes into a collection of segregated, nonoverlapping molecules.

PMID- 17025858
TI  - Multiple shear-banding transitions in a supramolecular polymer solution.
AB  - We report on the nonlinear rheology of a reversible supramolecular polymer based
      on hydrogen bonding. The coupling between the flow-induced chain alignment and
      breakage and recombination of bonds between monomers leads to a very unusual flow
      behavior. Measured velocity profiles indicate three different shear-banding
      regimes upon increasing shear rate, each with different characteristics. While
      the first of these regimes has features of a mechanical instability, the second
      shear-banding regime is related to a shear-induced phase separation and the
      appearance of birefringent textures. The shear-induced phase itself becomes
      unstable at very high shear rates, giving rise to a third banding regime.

PMID- 17025859
TI  - Comment on "Large slip of aqueous liquid flow over a nanoengineered
      superhydrophobic surface".

PMID- 17025861
TI  - Comment on "Spin-induced forbidden evanescent states in III-V semiconductors".

PMID- 17025863
TI  - Test of nonlocality for a continuous-variable state based on an arbitrary number
      of measurement outcomes.
AB  - We propose a scheme to test Bell's inequalities for an arbitrary number of
      measurement outcomes on entangled continuous-variable (CV) states. The Bell
      correlation functions are expressible in terms of phase-space quasiprobability
      functions with complex ordering parameters, which can experimentally be
      determined via a local CV-qubit interaction. We demonstrate that CV systems can
      give higher violations of these Bell's inequalities than of the ones developed
      for two-outcome observables.

PMID- 17025864
TI  - Nonexponential decay via tunneling in tight-binding lattices and the optical zeno
      effect.
AB  - An exactly-solvable model for the decay of a metastable state coupled to a semi
      infinite, tight-binding lattice, showing large deviations from exponential decay
      in the strong coupling regime, is presented. An optical realization of the
      lattice model, based on discrete diffraction in a semi-infinite array of
      tunneling-coupled optical waveguides, is proposed to test nonexponential decay
      and for the observation of an optical analog of the quantum Zeno effect.

PMID- 17025865
TI  - Quantum phase transitions in matrix product systems.
AB  - We investigate quantum phase transitions (QPTs) in spin chain systems
      characterized by local Hamiltonians with matrix product ground states. We show
      how to theoretically engineer such QPT points between states with predetermined
      properties. While some of the characteristics of these transitions are familiar,
      like the appearance of singularities in the thermodynamic limit, diverging
      correlation length, and vanishing energy gap, others differ from the standard
      paradigm: In particular, the ground state energy remains analytic, and the
      entanglement entropy of a half-chain stays finite. Examples demonstrate that
      these kinds of transitions can occur at the triple point of "conventional" QPTs.

PMID- 17025866
TI  - Magnetically tuned spin dynamics resonance.
AB  - We present the experimental observation of a magnetically tuned resonance
      phenomenon in the spin mixing dynamics of ultracold atomic gases. In particular,
      we study the magnetic field dependence of spin conversion in F=2 (87)Rb spinor
      condensates in the crossover from interaction dominated to quadratic Zeeman
      dominated dynamics. We discuss the observations in the framework of spin dynamics
      as well as matter wave four wave mixing. Furthermore, we show that the validity
      range of the single mode approximation for spin dynamics is significantly
      extended at high magnetic field.

PMID- 17025867
TI  - Unconventional strongly interacting bose-einstein condensates in optical
      lattices.
AB  - Feschbach resonances in a non-s-wave channel of two-component bosonic mixtures
      can induce atomic Bose-Einstein condensates with a nonzero orbital momentum in
      the optical lattice, if one component is in the Mott insulator state and the
      other is not. Such non-s-wave condensates break the symmetry of the lattice and,
      in some cases, time-reversal symmetry. They can be revealed in specific
      absorption imaging patterns.

PMID- 17025868
TI  - Splitting times of doubly quantized vortices in dilute bose-einstein condensates.
AB  - Recently, the splitting of a topologically created doubly quantized vortex into
      two singly quantized vortices was experimentally investigated in dilute atomic
      cigar-shaped Bose-Einstein condensates [Y. Shin, Phys. Rev. Lett. 93, 160406
      (2004)10.1103/PhysRevLett.93.160406]. In particular, the dependency of the
      splitting time on the peak particle density was studied. We present results of
      theoretical simulations which closely mimic the experimental setup. We show that
      the combination of gravitational sag and time dependency of the trapping
      potential alone suffices to split the doubly quantized vortex in time scales
      which are in good agreement with the experiments.

PMID- 17025869
TI  - Universal quantum computation with continuous-variable cluster states.
AB  - We describe a generalization of the cluster-state model of quantum computation to
      continuous-variable systems, along with a proposal for an optical implementation
      using squeezed-light sources, linear optics, and homodyne detection. For
      universal quantum computation, a nonlinear element is required. This can be
      satisfied by adding to the toolbox any single-mode non-Gaussian measurement,
      while the initial cluster state itself remains Gaussian. Homodyne detection alone
      suffices to perform an arbitrary multimode Gaussian transformation via the
      cluster state. We also propose an experiment to demonstrate cluster-based error
      reduction when implementing Gaussian operations.

PMID- 17025870
TI  - Delayed commutation in quantum computer networks.
AB  - In the same way that classical computer networks connect and enhance the
      capabilities of classical computers, quantum networks can combine the advantages
      of quantum information and communication. We propose a nonclassical network
      element, a delayed commutation switch, that can solve the problem of switching
      time in packet switching networks. With the help of some local ancillary qubits
      and superdense codes, we can route a qubit packet after part of it has left the
      network node.

PMID- 17025871
TI  - Preventing multipartite disentanglement by local modulations.
AB  - An entangled multipartite system coupled to a zero-temperature bath undergoes
      rapid disentanglement in many realistic scenarios due to local, symmetry-breaking
      differences in the particle-bath couplings. We show that locally controlled
      perturbations, addressing each particle individually, can impose a symmetry
      allowing the existence of decoherence-free multipartite entangled systems.

PMID- 17025872
TI  - Asymmetric response of a jammed plastic bead raft.
AB  - The successful development of an effective temperature would be an important step
      in the application of statistical mechanics principles to systems driven far from
      equilibrium. One direction that has shown promise is the use of fluctuation
      dissipation relations. However, driven systems break time-reversal symmetry, and
      understanding the implications of this for fluctuation-dissipation relations is a
      critical step in developing effective temperatures. Here we study the response
      function in a driven system of plastic beads as a function of the density in
      order to elucidate the generality of the use of fluctuation-dissipation
      relations. We find that even when a linear response is observed, the time scale
      of the response is dependent on the direction of the applied stress.

PMID- 17025873
TI  - Supernarrow spectral peaks near a kinetic phase transition in a driven nonlinear
      micromechanical oscillator.
AB  - We measure the spectral densities of fluctuations of an underdamped nonlinear
      micromechanical oscillator. By applying a sufficiently large periodic excitation,
      two stable dynamical states are obtained within a particular range of driving
      frequency. White noise is injected into the excitation, allowing the system to
      overcome the activation barrier and switch between the two states. While the
      oscillator predominately resides in one of the two states for most frequencies, a
      narrow range of frequencies exist where the occupations of the two states are
      approximately equal. At these frequencies, the oscillator undergoes a kinetic
      phase transition that resembles the phase transition of thermal equilibrium
      systems. We observe a supernarrow peak in the spectral densities of fluctuations
      of the oscillator. This peak is centered at the excitation frequency and arises
      as a result of noise-induced transitions between the two dynamical states.

PMID- 17025874
TI  - Density matrix renormalization group approach for many-body open quantum systems.
AB  - The density matrix renormalization group (DMRG) approach is extended to complex
      symmetric density matrices characteristic of many-body open quantum systems.
      Within the continuum shell model, we investigate the interplay between many-body
      configuration interaction and coupling to open channels in case of the unbound
      nucleus (7)He. It is shown that the extended DMRG procedure provides a highly
      accurate treatment of the coupling to the nonresonant scattering continuum.

PMID- 17025875
TI  - Chiral phase transition from string theory.
AB  - The low energy dynamics of a certain D-brane configuration in string theory is
      described at weak t'Hooft coupling by a nonlocal version of the Nambu-Jona
      Lasinio model. We study this system at finite temperature and strong t'Hooft
      coupling, using the string theory dual. We show that for sufficiently low
      temperatures chiral symmetry is broken, while for temperatures larger then the
      critical value, it gets restored. We compute the latent heat and observe that the
      phase transition is of the first order.

PMID- 17025880
TI  - Measurement of excited states in (40)Si and evidence for weakening of the N=28
      shell gap.
AB  - Excited states in (40)Si have been established by detecting gamma rays coincident
      with inelastic scattering and nucleon removal reactions on a liquid hydrogen
      target. The low excitation energy, 986(5) keV, of the 2(1)(+) state provides
      evidence of a weakening in the N=28 shell closure in a neutron-rich nucleus
      devoid of deformation-driving proton collectivity.

PMID- 17025881
TI  - Electromagnetically induced coherent backscattering.
AB  - We demonstrate a strong coherent backward wave oscillation using forward
      propagating fields only. This is achieved by applying laser fields to an
      ultradispersive medium with proper chosen detunings to excite a molecular
      vibrational coherence that corresponds to a backward propagating wave. The
      physics then has much in common with the propagation of ultraslow light.
      Applications to coherent scattering and remote sensing are discussed.

PMID- 17025882
TI  - Spectroscopic observation of the rotational Doppler effect.
AB  - We report on the first spectroscopic observation of the rotational Doppler shift
      associated with light beams carrying orbital angular momentum. The effect is
      evidenced as the broadening of a Hanle electromagnetically induced transparency
      coherence resonance on Rb vapor when the two incident Laguerre-Gaussian laser
      beams have opposite topological charges. The observations closely agree with
      theoretical predictions.

PMID- 17025883
TI  - Generation of narrow-bandwidth paired photons: use of a single driving laser.
AB  - We describe a generator of narrow-band paired photons. A single retroreflected
      Ti:sapphire laser is used to cool, render transparent, and parametrically pump a
      cloud of (87)Rb atoms. We attain a paired-photon generation rate into opposing
      fibers of 600 counts/s with an intensity correlation function that has a width of
      5 ns, and violates the Cauchy-Schwartz criteria by a factor of 2000.

PMID- 17025884
TI  - Direct measurement of decoherence for entanglement between a photon and stored
      atomic excitation.
AB  - Violations of a Bell inequality are reported for an experiment where one of two
      entangled qubits is stored in a collective atomic memory for a user-defined time
      delay. The atomic qubit is found to preserve the violation of a Bell inequality
      for storage times up to 21 micros, 700 times longer than the duration of the
      excitation pulse that creates the entanglement. To address the question of the
      security of entanglement-based cryptography implemented with this system, an
      investigation of the Bell violation as a function of the cross correlation
      between the generated nonclassical fields is reported, with saturation of the
      violation close to the maximum value allowed by quantum mechanics.

PMID- 17025885
TI  - Laser-assisted photoelectric effect from surfaces.
AB  - We report the first observation of the laser-assisted photoelectric effect from a
      solid surface. By illuminating a Pt(111) sample simultaneously with ultrashort
      1.6 eV and 42 eV pulses, we observe sidebands in the extreme ultraviolet
      photoemission spectrum. The magnitude of these sidebands as a function of time
      delay between the laser and extreme ultraviolet pulses represents a cross
      correlation measurement of the extreme ultraviolet pulse. This effect promises to
      be useful to extend extreme ultraviolet pulse duration measurements to higher
      photon energies, as well as opening up femtosecond-to-attosecond time-scale
      electron dynamics in solid and surface-adsorbate systems.

PMID- 17025886
TI  - Electric-field-induced polar biaxial order in a nontilted smectic phase of an
      asymmetric bent-core liquid crystal.
AB  - A polarization reorientation process has been studied by means of optical second
      harmonic generation in an optically uniaxial smectic phase of an asymmetric bent
      core liquid crystal. A nontilted polar smectic order with a biaxial order is
      induced by applying an electric field to the uniaxial nonpolar smectic phase.
      This phenomenon was well simulated by the two-dimensional Langevin process, i.e.,
      electric-field-induced continuous molecular reorientation against thermal
      agitation. The simulation suggests that about 200s of molecules form a polar
      domain and cooperatively respond to the applied field. The existence of the polar
      domains and their reorientation are consistent to the dielectric measurement; a
      high dielectric constant of about 60 at the kHz range is markedly suppressed by
      applying a bias field.

PMID- 17025879
TI  - Measurement of the N-->Delta(+)(1232) transition at high-momentum transfer by
      pi(0) electroproduction.
AB  - We report a new measurement of the exclusive electroproduction reaction gamma(*)p
      ->pi(0)p to explore the evolution from soft nonperturbative physics to hard
      processes via the Q(2) dependence of the magnetic (M(1+)), electric (E(1+)), and
      scalar (S(1+)) multipoles in the N-->Delta transition. 9000 differential cross
      section data points cover W from threshold to 1.4 GeV/c(2), 4pi center-of-mass
      solid angle, and Q(2) from 3 to 6 GeV(2)/c(2), the highest yet achieved. It is
      found that the magnetic form factor G(M)(*) decreases with Q(2) more steeply than
      the proton magnetic form factor, the ratio E(1+)/M(1+) is small and negative,
      indicating strong helicity nonconservation, and the ratio S(1+)/M(1+) is
      negative, while its magnitude increases with Q(2).

PMID- 17025887
TI  - Non-Gibbsian stochastic light-mode dynamics of passive mode locking.
AB  - We study a stochastic light-mode system with non-Gibbsian steady state
      statistics, unravelling global nonequilibrium phase transition properties. It
      relates to the onset of passive mode-locking in the general case of lasers with
      arbitrary dispersion and Kerr nonlinearity that includes the nonsolitonic regime.
      The solution is facilitated by a special stationarity criterion imposed by the
      system gain balance. We show that the mode-locking phase transition is generic,
      and give exact expressions for the pulse power and its stability map. We find
      that at the boundary of the mode-locking stability the pulse power is exactly one
      half of the total intracavity power, and that the parameter region for the most
      resistant pulses against noise destabilization is not at the soliton condition.

PMID- 17025888
TI  - Self-induced chaos in a single-mode inversionless laser.
AB  - A single-mode inversionless laser with a three-level phaseonium as an active
      medium can by itself exhibit complex nonlinear dynamics. Nonlinear interaction
      between two spectrally separated gain regions of the phaseonium and a lasing
      field gives rise to instabilities and chaotic self-pulsations of a type not
      observed in conventional lasers with population-inverted gain media. We calculate
      the bifurcation diagram and uncover multistability and a torus-doubling cascade
      in transition to chaos.

PMID- 17025889
TI  - Ring intermittency in coupled chaotic oscillators at the boundary of phase
      synchronization.
AB  - A new type of intermittent behavior is described to occur near the boundary of
      the phase synchronization regime of coupled chaotic oscillators. This mechanism,
      called ring intermittency, arises for sufficiently high initial mismatches in the
      frequencies of the two coupled systems. The laws for both the distribution and
      the mean length of the laminar phases versus the coupling strength are
      analytically deduced. Very good agreement between the theoretical results and the
      numerically calculated data is shown. We discuss how this mechanism is expected
      to take place in other relevant physical circumstances.

PMID- 17025890
TI  - Wannier-stark ladders in one-dimensional elastic systems.
AB  - The optical analogues of Bloch oscillations and their associated Wannier-Stark
      ladders have been recently analyzed. In this Letter we propose an elastic
      realization of these ladders, employing for this purpose the torsional vibrations
      of specially designed one-dimensional elastic systems. We have measured, for the
      first time, the ladder wave amplitudes, which are not directly accessible either
      in the quantum-mechanical or optical cases. The wave amplitudes are spatially
      localized and coincide rather well with theoretically predicted amplitudes. The
      rods we analyze can be used to localize different frequencies in different parts
      of the elastic systems and vice versa.

PMID- 17025891
TI  - Hydrodynamic self-consistent field theory for inhomogeneous polymer melts.
AB  - We introduce a mesoscale technique for simulating the structure and rheology of
      block-copolymer melts and blends in hydrodynamic flows. The technique couples
      dynamic self-consistent field theory with continuum hydrodynamics and flow
      penalization to simulate polymeric fluid flows in channels of arbitrary geometry.
      We demonstrate the method by studying phase separation of an ABC triblock
      copolymer melt in a submicron channel with neutral wall wetting conditions. We
      find that surface wetting effects and shear effects compete, producing wall
      perpendicular lamellae in the absence of flow and wall-parallel lamellae in cases
      where the shear rate exceeds some critical Weissenberg number.

PMID- 17025892
TI  - Cutoff wave number for shear waves in a two-dimensional Yukawa system (dusty
      plasma).
AB  - The cutoff wave number for shear waves in a liquid-state strongly coupled plasma
      was measured experimentally. The phonon spectra of random particle motion were
      measured at various temperatures in a monolayer dusty plasma, where microspheres
      interact with a Yukawa potential. In the liquid state of this particle
      suspension, shear waves were detected only for wavelengths smaller than 20 to 40
      Wigner-Seitz radii, depending on the Coulomb coupling parameter. The temperature
      of the suspension was controlled using a laser-heating method.

PMID- 17025877
TI  - Measurement of the spin of the omega(-) hyperon.
AB  - A measurement of the spin of the Omega(-) hyperon produced through the exclusive
      process Xi(c)(0)-->Omega(-)K(+) is presented using a total integrated luminosity
      of 116 fb(-1) recorded with the BABAR detector at the e(+)e(-) asymmetric-energy
      B factory at SLAC. Under the assumption that the Xi(c)(0) has spin 1/2, the
      angular distribution of the Lambda from Omega(-)-->LambdaK(-) decay is
      inconsistent with all half-integer Omega(-) spin values other than 3/2. Lower
      statistics data for the process Omega(c)(0)-->Omega(-)pi(+) from a 230 fb(-1)
      sample are also found to be consistent with Omega(-) spin 3/2. If the Xi(c)(0)
      spin were 3/2, an Omega(-) spin of 5/2 could not be excluded.

PMID- 17025893
TI  - Theory of laser acceleration of light-ion beams from interaction of ultrahigh
      intensity lasers with layered targets.
AB  - Experiments at the LANL Trident facility demonstrated the production of
      monoenergetic ion beams from the interaction of an ultraintense laser with a
      target comprising a heavy ion substrate and thin layer of light ions. An analytic
      model is obtained that predicts how the mean energy and quality of monoenergetic
      ion beams and the energy of substrate ions vary with substrate material and light
      ion layer composition and thickness. Dimensionless parameters controlling the
      dynamics are derived and the model is validated with particle-in-cell simulations
      and experimental data.

PMID- 17025894
TI  - Spheromak formation by steady inductive helicity injection.
AB  - A spheromak is formed for the first time using a new steady state inductive
      helicity injection method. Using two inductive injectors with odd symmetry and
      oscillating at 5.8 kHz, a steady state spheromak with even symmetry is formed and
      sustained through nonlinear relaxation. A spheromak with about 13 kA of toroidal
      current is formed and sustained using about 3 MW of power. This is a much lower
      power threshold for spheromak production than required for electrode-based
      helicity injection. Internal magnetic probe data, including oscillations driven
      by the injectors, agree with the plasma being in the Taylor state. The agreement
      is remarkable considering the only fitting parameter is the amplitude of the
      spheromak component of the state.

PMID- 17025878
TI  - Observation of e(+)e(-) annihilation into the C = +1 hadronic final states
      rho(0)rho(0) and phirho(0).
AB  - We report the first observation of e(+)e(-) annihilation into states of positive
      C parity, namely, rho(0)rho(0) and phirho(0). The two states are observed in the
      pi(+)pi(-)pi(+)pi(-) and K(+)K(-)pi(+)pi(-) final states, respectively, in a data
      sample of 225 fb(-1) collected by the BABAR experiment at the Positron-Electron
      Project II e(+)e(-) storage rings at energies near sqrt[s]=10.58 GeV. The
      distributions of costheta(*), where theta(*) is the center-of-mass polar angle of
      the phi meson or the forward rho(0) meson, suggest production by two-virtual
      photon annihilation. We measure cross sections within the range |costheta(*)|<0.8
      of sigma(e(+)e(-)-->rho(0)rho(0))=20.7+/-0.7(stat)+/-2.7(syst) fb and
      sigma(e(+)e(-)-->phirho(0))=5.7+/-0.5(stat)+/-0.8(syst) fb.

PMID- 17025895
TI  - Collective modes and f-wave pairing interactions in superfluid (3)He.
AB  - Precision measurements of collective mode frequencies in superfluid (3)He-B are
      sensitive to quasiparticle and f-wave pairing interactions. Measurements were
      performed at various pressures using interference of transverse sound in an
      acoustic cavity. We fit the measured collective mode frequencies, which depend on
      the strength of f-wave pairing and the Fermi liquid parameter F(2)(s), to
      theoretical predictions and discuss what implications these values have for
      observing new order parameter collective modes.

PMID- 17025896
TI  - Supersolid helium at high pressure.
AB  - We have measured the pressure dependence of the supersolid fraction by a
      torsional oscillator technique. Superflow is found from 25.6 bar up to 136.9 bar.
      The supersolid fraction in the low temperature limit increases from 0.6% at 25.6
      bar near the melting boundary up to a maximum of 1.5% near 55 bar before showing
      a monotonic decrease with pressure extrapolating to zero near 170 bar.

PMID- 17025876
TI  - Search for resonant second generation slepton production at the Fermilab
      Tevatron.
AB  - We present a search for supersymmetry in the R-parity violating resonant
      production and decay of smuons and muon sneutrinos in the channels mu-
      >chi(1)(0)mu, mu-->chi(2,3,4)(0)mu, and nu(mu)-->chi(1,2)(+/-)mu. We analyzed
      0.38 fb(-1) of integrated luminosity collected between April 2002 and August 2004
      with the D0 detector at the Fermilab Tevatron Collider. The observed number of
      events is in agreement with the standard model expectation, and we calculate 95%
      C.L. limits on the slepton production cross section times branching fraction to
      gaugino plus muon, as a function of slepton and gaugino masses. In the framework
      of minimal supergravity, we set limits on the coupling parameter lambda(211)('),
      extending significantly previous results obtained in Run I of the Tevatron and at
      the CERN LEP collider.

PMID- 17025897
TI  - Apparently complex high-pressure phase of gallium as a simple modulated
      structure.
AB  - The phase of gallium GaII, with symmetry C222(1) and 104 atoms per unit cell, has
      been recently reported as an example of structural complexity under high
      pressure. It is shown here that this phase is a simple modulated distortion of an
      average structure of Fddd symmetry with all atoms structurally equivalent. The
      modulation can be described with only 4 parameters and satisfies symmetry
      properties described by a centrosymmetric superspace group. The structural
      distortion is dominated by a frozen transversal mode associated with a single
      irreducible representation of Fddd, with a wave vector on the line Q, at an edge
      of the Brillouin zone. The average structure can be related with an hcp
      configuration through simple sliding of hcp layers, reminiscent of the hcp-bcc
      Burgers mechanism.

PMID- 17025898
TI  - Subterahertz phonon dynamics in acoustic nanocavities.
AB  - We report a direct determination of the dynamic behavior of confined acoustic
      phonons in nanocavities by picosecond acoustics. We provide the broadband, high
      resolution transmission amplitude curve in the subterahertz range, and we give
      evidence of resonant transmission peaks in three successive stop bands, in
      quantitative agreement with acoustic simulations. We furthermore demonstrate
      transit times in the nanosecond range at the cavity peaks reflecting the strong
      confinement of resonant phonons within the cavity layer. On the other hand,
      picosecond transit times are measured in the stop band, shorter than in any of
      the constituting materials, a tunneling effect well known both in photonic
      crystals and in macroscopic phononic systems.

PMID- 17025899
TI  - Adding a length scale to the polyamorphic ice debate.
AB  - X-ray scattering and molecular dynamics simulations have been used to correlate
      the short range oxygen-oxygen structure with the intermediate range ordering
      (IRO) upon annealing very high density amorphous ice. While it is clear that the
      IRO that defines the network structure breaks down continuously to a minimum
      level, where there are weakened correlations extending beyond 7 Angstrom, at this
      point the local structure (O-O-O angles) is observed to change abruptly, allowing
      a continuous reemergence of a new IRO network. This is very different from a
      classic first order transition and helps reconcile previous data.

PMID- 17025900
TI  - Self-propulsion of nematic drops: novel phase separation dynamics in impurity
      doped nematogens.
AB  - We report a novel phase separation dynamics, mediated by self-propelled motion of
      the nucleated drops, in a mixture of a nematogen and an isotropic dopant. We show
      that surface flow, induced by the gradient in the concentration of the dopant
      expelled by the growing drops, provides the driving force for the propulsion of
      nematic droplets. While the liquid crystal-isotropic transition is used here to
      demonstrate the phenomenon, self-propulsion should be observable in many other
      systems in which the dynamics of a conserved order parameter is coupled to a
      nonconserved order parameter.

PMID- 17025901
TI  - Anchored critical percolation clusters and 2D electrostatics.
AB  - We consider the densities of clusters, at the percolation point of a two
      dimensional system, which are anchored in various ways to an edge. These
      quantities are calculated by use of conformal field theory and computer
      simulations. We find that they are given by simple functions of the potentials of
      2D electrostatic dipoles and that a kind of superposition cum factorization
      applies. Our results broaden this connection, already known from previous
      studies, and we present evidence that it is more generally valid. An exact result
      similar to the Kirkwood superposition approximation emerges.

PMID- 17025902
TI  - Quantum phase transitions of hard-core bosons in background potentials.
AB  - We study the zero temperature phase diagram of hard-core bosons in two dimensions
      subjected to three types of background potentials: staggered, uniform, and
      random. In all three cases there is a quantum phase transition from a superfluid
      (at small potential) to a normal phase (at large potential), but with different
      universality classes. As expected, the staggered case belongs to the XY
      universality, while the uniform potential induces a mean field transition. The
      disorder driven transition is clearly different from both; in particular, we find
      z approximately 1.4, nu approximately 1, and beta approximately 0.6.

PMID- 17025903
TI  - Excitation chains at the glass transition.
AB  - The excitation-chain theory of the glass transition, proposed in an earlier
      publication, predicts diverging, super-Arrhenius relaxation times and, via a
      similarly diverging length scale, suggests a way of understanding the relations
      between dynamic and thermodynamic properties of glass-forming liquids. I argue
      here that critically large excitation chains play a role roughly analogous to
      that played by critical clusters in the droplet model of vapor condensation.
      Unlike a first-order condensation point in a vapor, the glass transition is not a
      conventional phase transformation, and may not be a thermodynamic transition at
      all.

PMID- 17025904
TI  - Simulation of phase transitions in highly asymmetric fluid mixtures.
AB  - We present a novel method for the accurate numerical determination of the phase
      behavior of fluid mixtures having large particle-size asymmetries. By
      incorporating the recently developed geometric cluster algorithm within a
      restricted Gibbs ensemble, we are able to probe directly the density and
      concentration fluctuations that drive phase transitions, but that are
      inaccessible to conventional simulation algorithms. We develop a finite-size
      scaling theory that relates these density fluctuations to those of the grand
      canonical ensemble, thereby enabling accurate location of critical points and
      coexistence curves of multicomponent fluids. Several illustrative examples are
      presented.

PMID- 17025905
TI  - Spin thermal conductivity of the haldane chain compound Y(2)BaNiO(5).
AB  - We have measured the thermal conductivity of the spin S=1 chain compound
      Y(2)BaNiO(5). Analyzing the anisotropy of the thermal transport allows us to
      identify a definite spin-mediated thermal conductivity kappa(s) along the chain
      direction. The calculated spin-related energy diffusion constant D(E)(T) shows a
      broad peak around 120 K. Close to room temperature, D(E)(T) approaches the
      theoretically predicted high-temperature value, while scattering of spin
      excitations by magnetic impurities seems to be the major limiting factor of
      kappa(s) at low temperature.

PMID- 17025906
TI  - Oxygen migration, agglomeration, and trapping: key factors for the morphology of
      the Si-SiO(2) interface.
AB  - The measured activation energies for oxide growth rates at the initial and late
      stages of oxidation of Si are 2 and 1.2 eV, respectively. These values imply that
      oxidation can proceed at temperatures much smaller than the 800 degrees C
      normally used to obtain devices with exceptionally smooth Si-SiO2 interfaces.
      Here, we use first-principles calculations to identify the atomic-scale
      mechanisms of the 2 eV process and of additional processes with higher barriers
      that control the interface morphology and ultimately provide for smooth layer-by
      layer oxide growth, as observed at high temperatures.

PMID- 17025907
TI  - Trapping-mediated chemisorption of ethylene on Si(001)-c(4 x 2).
AB  - Adsorption of ethylene molecules on Si(001)-c(4 x 2) was studied using scanning
      tunneling microscopy at low temperatures. Ethylene molecules trapped at the
      surface at 50 K were imaged only after decay to chemisorption, each bonding to a
      Si dimer. Atomic-scale observations of temperature-dependent kinetics show that
      the decay exhibited Arrhenius behavior with the reaction barrier of 128 meV in
      clear evidence of the trapping-mediated chemisorption, however, with an
      anomalously small preexponential factor of 300 Hz. Such a small prefactor is
      attributed to the entropic bottleneck at the transition state caused by the free
      molecule-like trap state.

PMID- 17025908
TI  - Influence of surface roughness on superhydrophobicity.
AB  - Superhydrophobic surfaces, with a liquid contact angle theta greater than 150
      degrees , have important practical applications ranging from self-cleaning window
      glasses, paints, and fabrics to low-friction surfaces. Many biological surfaces,
      such as the lotus leaf, have a hierarchically structured surface roughness which
      is optimized for superhydrophobicity through natural selection. Here we present a
      molecular dynamics study of liquid droplets in contact with self-affine fractal
      surfaces. Our results indicate that the contact angle for nanodroplets depends
      strongly on the root-mean-square surface roughness amplitude but is nearly
      independent of the fractal dimension D(f) of the surface.

PMID- 17025909
TI  - Coherent peaks and minimal probing depth in photoemission spectroscopy of Mott
      Hubbard systems.
AB  - We have measured hard x-ray photoemission spectra of pure vanadium sesquioxide
      (V(2)O(3)) across its metal-insulator transition. We show that, in the metallic
      phase, a clear correlation exists between the shakedown satellites observed in
      the vanadium 2p and 3p core-level spectra and the coherent peak measured at the
      Fermi level. Comparing experimental results and dynamical mean-field theory
      calculations, we estimate the Hubbard energy U in V(2)O(3) (4.20+/-0.05 eV). From
      our bulk-sensitive photoemission spectra we infer the existence of a critical
      probing depth for investigating electronic properties in strongly correlated
      solids.

PMID- 17025910
TI  - Transfer of spectral weight and symmetry across the metal-insulator transition in
      VO(2).
AB  - We present a detailed study of the valence and conduction bands of VO2 across the
      metal-insulator transition using bulk-sensitive photoelectron and O K x-ray
      absorption spectroscopies. We observe a giant transfer of spectral weight with
      distinct features that require an explanation which goes beyond the Peierls
      transition model as well as the standard single-band Hubbard model. Analysis of
      the symmetry and energies of the bands reveals the decisive role of the V 3d
      orbital degrees of freedom. Comparison to recent realistic many body calculations
      shows that much of the k dependence of the self-energy correction can be cast
      within a dimer model.

PMID- 17025911
TI  - Minimal excitation states of electrons in one-dimensional wires.
AB  - A strategy is proposed to excite particles from a Fermi sea in a noise-free
      fashion by electromagnetic pulses with realistic parameters. We show that by
      using quantized pulses of simple form one can suppress the particle-hole pairs
      which are created by a generic excitation. The resulting many-body states are
      characterized by one or several particles excited above the Fermi surface
      accompanied by no disturbance below it. These excitations carry charge which is
      integer for noninteracting electron gas and fractional for Luttinger liquid. The
      operator algebra describing these excitations is derived, and a method of their
      detection which relies on noise measurement is proposed.

PMID- 17025912
TI  - Electron localization or delocalization in incommensurate helical magnets.
AB  - The electronic states in incommensurate helical magnets are studied theoretically
      from the viewpoint of the localization or delocalization. It is found that in the
      multiband system with a relativistic spin-orbit interaction, the electronic wave
      functions show both an extended and localized nature along the helical axis
      depending on the orbital, helical wave number, and the direction of the plane on
      which spins rotate. The possible realization of this localization is discussed.

PMID- 17025913
TI  - A solid state paramagnetic maser device driven by electron spin injection.
AB  - In response to an external, microwave-frequency magnetic field, a paramagnetic
      medium will absorb energy from the field that drives the magnetization dynamics.
      Here we describe a new process by which an external spin-injection source, when
      combined with the microwave field spin pumping, can drive the paramagnetic medium
      from one that absorbs microwave energy to one that emits microwave energy. We
      derive a simple condition for the crossover from absorptive to emissive behavior.
      Based on this process, we propose a solid-state, paramagnetic device in which
      microwave amplification by stimulated emission of radiation is driven by spin
      injection.

PMID- 17025914
TI  - Cycloaddition functionalizations to preserve or control the conductance of carbon
      nanotubes.
AB  - We identify a class of covalent functionalizations that preserve or control the
      conductance of single-walled metallic carbon nanotubes. [2+1] cycloadditions can
      induce bond cleaving between adjacent sidewall carbons, recovering in the process
      the sp;{2} hybridization and the ideal conductance of the pristine tubes. This is
      radically at variance with the damage permanently induced by other common
      ligands, where a single covalent bond is formed with a sidewall carbon.
      Chirality, curvature, and chemistry determine bond cleaving, and in turn the
      electrical transport properties of a functionalized tube. A well-defined range of
      diameters can be found for which certain addends exhibit a bistable state, where
      the opening or closing of the sidewall bond, accompanied by a switch in the
      conductance, could be directed with chemical, optical, or thermal means.

PMID- 17025915
TI  - One-dimensional plasmon in an atomic-scale metal wire.
AB  - We have measured one-dimensional (1D) plasmons in an atom wire array on the
      Si(557)-Au surface by inelastic scattering of a highly collimated slow electron
      beam. The angular dependence of the excitation energy clearly indicates the
      strong 1D confinement and free propagation of the plasma wave along the wire. The
      observed plasmon dispersion is explained very well by a quantum-mechanical scheme
      which takes into account dynamic exchange-correlation effects, interwire
      interactions, and spin-orbit splitting of the 1D bands. Although the qualitative
      feature of the plasmon dispersion is reminiscent of that of a high-density free
      electron gas, we detected the substantial influence of electron correlation due
      to strong 1D confinement.

PMID- 17025916
TI  - Dependence of persistent gaps at landau level crossings on relative spin.
AB  - We report measurements of the quantum Hall state energy gap at avoided crossings
      between Landau levels originating from different conduction band valleys in AlAs
      quantum wells. These gaps exhibit an approximately linear dependence on the
      magnetic field over a wide range of fields and filling factors. More remarkably,
      we observe an unexpected dependence of the gap size on the relative spin
      orientation of the crossing levels, with parallel-spin crossings exhibiting
      larger gaps than antiparallel-spin crossings.

PMID- 17025917
TI  - Nanowires with surface disorder: giant localization lengths and quantum-to
      classical crossover.
AB  - We investigate electronic quantum transport through nanowires with one-sided
      surface roughness. A magnetic field perpendicular to the scattering region is
      shown to lead to exponentially diverging localization lengths in the quantum-to
      classical crossover regime. This effect can be quantitatively accounted for by
      tunneling between the regular and the chaotic components of the underlying mixed
      classical phase space.

PMID- 17025918
TI  - Luttinger liquid at the edge of undoped graphene in a strong magnetic field.
AB  - We demonstrate that an undoped two-dimensional carbon plane (graphene) whose bulk
      is in the integer quantum Hall regime supports a nonchiral Luttinger liquid at an
      armchair edge. This behavior arises due to the unusual dispersion of the
      noninteracting edge states, causing a crossing of bands with different valley and
      spin indices at the edge. We demonstrate that this stabilizes a domain wall
      structure with a spontaneously ordered phase degree of freedom. This coherent
      domain wall supports gapless charged excitations, and has a power law tunneling I
      V with a nonintegral exponent. In proximity to a bulk lead, the edge may undergo
      a quantum phase transition between the Luttinger liquid phase and a metallic
      state.

PMID- 17025919
TI  - Qubit measurements with a double-dot detector.
AB  - We propose to monitor a qubit with a double-dot (DD) resonant-tunneling detector,
      which can operate at higher temperatures than a single-dot detector. In order to
      assess the effectiveness of this device, we derive rate equations for the density
      matrix of the entire system. We show that the signal-to-noise ratio can be
      greatly improved by a proper choice of the parameters and location of the
      detector. We demonstrate that quantum interference effects within the DD detector
      play an important role in the measurement. Surprisingly, these effects produce a
      systematic measurement error, even when the entire system is in a stationary
      state.

PMID- 17025920
TI  - Suppression of superconductivity in disordered interacting wires.
AB  - We study superconductivity suppression due to thermal fluctuations in disordered
      wires using the replica nonlinear sigma-model (NLsigmaM). We show that in
      addition to the thermal phase slips there is another type of fluctuations that
      result in a finite resistivity. These fluctuations are described by saddle points
      in NLsigmaM and cannot be treated within the Ginzburg-Landau approach. The
      contribution of such fluctuations to the wire resistivity is evaluated with
      exponential accuracy. The magnetoresistance associated with this contribution is
      negative.

PMID- 17025921
TI  - Observation of spin susceptibility enhancement in the possible Fulde-Ferrell
      Larkin-Ovchinnikov state of CeCoIn(5).
AB  - We report (115)In nuclear magnetic resonance measurements of the heavy-fermion
      superconductor CeCoIn(5) in the vicinity of the superconducting critical field
      H(c2) for a magnetic field applied perpendicular to the c axis. A possible
      inhomogeneous superconducting state, the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO)
      state, is stabilized in this part of the phase diagram. In an 11 T applied
      magnetic field, we observe clear signatures of the two phase transitions: the
      higher temperature one to the homogeneous superconducting state and the lower
      temperature phase transition to a FFLO state. We find that the spin
      susceptibility in the putative FFLO state is significantly enhanced as compared
      to the value in a homogeneous superconducting state. The implications of this
      finding for the nature of the low temperature phase are discussed.

PMID- 17025922
TI  - Role of inelastic tunneling through the insulating barrier in scanning-tunneling
      microscope experiments on cuprate superconductors.
AB  - The tunneling path between the CuO2 layers in cuprate superconductors and a
      scanning-tunneling-microscope tip passes through a barrier made from other oxide
      layers. This opens up the possibility that inelastic processes in the barrier
      contribute to the tunneling spectra. Such processes cause one or possibly more
      peaks in the second derivative current-voltage spectra displaced by phonon
      energies from the density of states singularity associated with
      superconductivity. Calculations of inelastic processes generated by apical O
      phonons show good qualitative agreement with recent experiments reported by Lee
      et al. Further tests to discriminate between these inelastic processes and
      coupling to planar phonons are proposed.

PMID- 17025923
TI  - Metal-insulator transition in a system of superconducting vortices caused by a
      metallic gate.
AB  - We address a recent experiment in which a strong decrease of the resistance of a
      superconducting film has been observed when a remote unbiased gate was placed
      above the film. Here we explain the experimental finding as a suppression of the
      vortex tunneling due to the orthogonality catastrophe of the electrons inside the
      gate. We interpret the change in the resistance of the film as a "metal
      insulator" transition in the system of vortices induced by the gate.

PMID- 17025924
TI  - Enhanced orbital magnetism in Fe(50)Pt(50) nanoparticles.
AB  - X-ray absorption and magnetic circular dichroism spectra at both the Fe and Pt
      L(3,2) edges were measured on wet-chemically synthesized monodisperse
      Fe(50)Pt(50) particles with a mean diameter of 6.3 nm before and after complete
      removal of the organic ligands and the oxide shell covering the particles by soft
      hydrogen plasma resulting in a pure metallic state. After thermal treatment of
      the metallic particles, the coercive field increased by a factor of 6, the
      orbital magnetic moment at the Fe site increased by 330% and is reduced at the Pt
      site by 30%, while the effective spin moments did not change. A decrease of the
      frequency of oscillations in the extended x-ray absorption fine structure at the
      Pt L(3,2) edges provides evidence for crystallographic changes towards the L1(0)
      phase.

PMID- 17025925
TI  - Extended scaling scheme for critically divergent quantities in ferromagnets and
      spin glasses.
AB  - From a consideration of high temperature series expansions in ferromagnets and in
      spin glasses, we propose an extended scaling scheme involving a set of scaling
      formulas which expresses to leading order the temperature (T) and the system size
      (L) dependences of thermodynamic observables over a much wider range of T than
      the corresponding one in the conventional scaling scheme. The extended scaling,
      illustrated by data on the canonical 2d ferromagnet and on the 3d bimodal Ising
      spin glass, leads to consistency in the estimates of critical parameters obtained
      from scaling analyses for different observables.

PMID- 17025926
TI  - Direct evidence for a dynamical ground state in the highly frustrated
      Tb(2)Sn(2)O(7) pyrochlore.
AB  - mSR experiments have been performed on a powder sample of the "ordered spin ice"
      Tb(2)Sn(2)O(7) pyrochlore. At base temperature (T=35 mK), the muon relaxation is
      found to be of dynamical nature, which demonstrates that strong fluctuations
      persist below the ferromagnetic transition (T(C)=0.87 K). Hints of long-range
      ordering appear as oscillations of the muon polarization when an external field
      is applied and also as a hysteretic behavior below T(C). We propose that dynamics
      results from fluctuations of clusters of correlated spins with the ordered spin
      ice structure.

PMID- 17025927
TI  - Low-energy dynamics of the two-dimensional S=1/2 Heisenberg antiferromagnet on
      percolating clusters.
AB  - We investigate the quantum dynamics of site diluted S=1/2 Heisenberg
      antiferromagnetic clusters at the 2D percolation threshold. We use Lanczos
      diagonalization to calculate the lowest excitation gap Delta and, to reach larger
      sizes, use quantum Monte Carlo simulations to study an upper bound for Delta
      obtained from sum rules involving the staggered structure factor and
      susceptibility. Scaling the gap distribution with the cluster length L, Delta
      approximately L(-), we obtain a dynamic exponent z approximately 2D(f), where
      D(f)=91/48 is the fractal dimensionality of the percolating cluster. This is in
      contrast with previous expectations of z=D(f). We argue that the low-energy
      excitations are due to weakly coupled effective moments formed due to local
      imbalance in sublattice occupation.

PMID- 17025928
TI  - Large excitonic enhancement of optical refrigeration in semiconductors.
AB  - We present a theoretical analysis for laser cooling of bulk GaAs based on a
      microscopic many-particle theory of absorption and luminescence of a partially
      ionized electron-hole plasma. Our cooling threshold analysis shows that, at low
      temperatures, the presence of the excitonic resonance in the luminescence is
      essential in competing against heating losses. The theory includes self
      consistent energy renormalizations and line broadenings from both instantaneous
      mean-field and frequency-dependent carrier-carrier correlations, and it is
      applicable from the few-Kelvin regime to above room temperature.

PMID- 17025929
TI  - Force control between quantum dots by light in polaritonic molecule states.
AB  - Photomediated force between quantum dots (QDs) is theoretically studied. An
      attractive (repulsive) interparticle radiation force (IRF) arises by selectively
      exciting the lower (higher) split state of coupled polaritons in QDs. Since these
      states are analogous to bonding and antibonding states of a diatomic molecule, we
      term this system the "polaritonic molecule (PM)". IRF in PM states is controlled
      by the photon energy, polarization, and phase at each QD. This mechanism can be
      used to probe internal quantum properties of nano-objects and to manipulate
      collective dynamics of QDs.

PMID- 17025930
TI  - Origin of increase of damping in transition metals with rare-earth-metal
      impurities.
AB  - The damping due to rare-earth-metal impurities in transition metals is discussed
      in the low concentration limit. It is shown that all established damping
      mechanisms based on spin-orbit and/or spin-spin interactions cannot explain
      experimental observations even qualitatively. We introduce a different relaxation
      channel due to the coupling of the orbital moments of the rare-earth-metal
      impurities and the conduction p electrons that leads to good agreement with
      experiment. Using an itinerant picture for the host ions, i.e., write their
      magnetization in terms of the electronic degrees of freedom, is key to the
      success of our model.

PMID- 17025931
TI  - Solitary modes of bacterial culture in a temperature gradient.
AB  - We study the behavior of a bacterial culture in a one-dimensional temperature
      gradient. The bacteria first accumulate near their natural temperature due to
      thermotaxis. The maximum of the bacterial density profile then drifts to lower
      temperature with a velocity proportional to the initial concentration of bacteria
      (typical velocity 0.5 microm/sec). Above a critical concentration of 10(8)
      cells/cm(3), a new mode develops from the initial accumulation in the form of a
      sharp pulse moving at a faster velocity ( approximately 3.5 microm/sec). The time
      of development of this mode diverges as the concentration approaches its critical
      value. This mode is a result of a positive feedback mechanism provided by
      interbacterial communication. A theoretical model shows good agreement with the
      experimental results.

PMID- 17025932
TI  - Does the 1/f frequency scaling of brain signals reflect self-organized critical
      states?
AB  - Many complex systems display self-organized critical states characterized by 1/f
      frequency scaling of power spectra. Global variables such as the
      electroencephalogram, scale as 1/f, which could be the sign of self-organized
      critical states in neuronal activity. By analyzing simultaneous recordings of
      global and neuronal activities, we confirm the 1/f scaling of global variables
      for selected frequency bands, but show that neuronal activity is not consistent
      with critical states. We propose a model of 1/f scaling which does not rely on
      critical states, and which is testable experimentally.

PMID- 17025933
TI  - Isotropic to nematic liquid crystalline phase transition of F-actin varies from
      continuous to first order.
AB  - We report that the properties of the isotropic to nematic liquid crystalline
      phase transition of F-actin depend critically on the average filament length. For
      average filament lengths longer than 2 microm, we confirm previous findings that
      the phase transition is continuous in both alignment and concentration. For
      average filament lengths shorter than 2 microm, we show for the first time a
      first order transition with a clear discontinuity in both alignment and
      concentration. Tactoidal droplets of coexisting isotropic and nematic phases,
      differing in concentration by approximately 30%, form over the course of hours
      and appear to settle into near equilibrium metastable states.

PMID- 17025934
TI  - Dynamical slowdown of polymers in laminar and random flows.
AB  - The influence of an external flow on the relaxation dynamics of a single polymer
      is investigated theoretically and numerically. We show that a pronounced
      dynamical slowdown occurs in the vicinity of the coil-stretch transition,
      especially when the dependence on polymer conformation of the drag is accounted
      for. For the elongational flow, relaxation times are exceedingly larger than the
      Zimm relaxation time, resulting in the observation of conformation hysteresis.
      For random smooth flows, hysteresis is not present. Yet, relaxation dynamics is
      significantly slowed down because of the large variety of accessible polymer
      configurations. The implications of these results for the modeling of dilute
      polymer solutions in turbulent flows are addressed.

PMID- 17025935
TI  - Comment on "Structural stability of complex hydrides: LiBH(4) revisited".

PMID- 17025937
TI  - Comment on "Photoemission study of YBa(2)Cu(3)O(y) thin films under light
      illumination".

PMID- 17025939
TI  - Comment on "Evidence of many-particle interactions in two-dimensional charge
      stabilized colloidal crystals".

PMID- 17025940
TI  - Detecting the breached-pair phase in a polarized ultracold Fermi gas.
AB  - We propose a method for the experimental detection of a new quantum phase, the
      breached-pair state, in a strongly interacting ultracold Fermi gas with
      population imbalance. We show that through the time-of-flight Raman imaging, the
      presence of such a phase can be unambiguously determined with a measurement of
      the momentum-space phase separation of the minority spin component. To guide the
      experimental efforts, the momentum-space density profiles are calculated under
      typical experimental conditions.

PMID- 17025941
TI  - Ultracold heteronuclear molecules in a 3D optical lattice.
AB  - We report on the creation of ultracold heteronuclear molecules assembled from
      fermionic 40K and bosonic 87Rb atoms in a 3D optical lattice. Molecules are
      produced at a heteronuclear Feshbach resonance on both the attractive and the
      repulsive sides of the resonance. We precisely determine the binding energy of
      the heteronuclear molecules from rf spectroscopy across the Feshbach resonance.
      We characterize the lifetime of the molecular sample as a function of magnetic
      field and measure lifetimes between 20 and 120 ms. The efficiency of molecule
      creation via rf association is measured and is found to decrease as expected for
      more deeply bound molecules.

PMID- 17025942
TI  - Tuning of heteronuclear interactions in a degenerate Fermi-Bose mixture.
AB  - We demonstrate tuning of interactions between fermionic 40K and bosonic 87Rb
      atoms by Feshbach resonances and access the complete phase diagram of the
      harmonically trapped mixture from phase separation to collapse. On the attractive
      side of the resonance, we observe a strongly enhanced mean-field energy of the
      condensate due to the mutual mean-field confinement, predicted by a Thomas-Fermi
      model. As we increase heteronuclear interactions beyond a threshold, we observe
      an induced collapse of the mixture. On the repulsive side of the resonance, we
      observe vertical phase separation of the mixture in the presence of the
      gravitational force, thus entering a completely unexplored part of the phase
      diagram of the mixture. In addition, we identify the 515 G resonance as p wave by
      its characteristic doublet structure.

PMID- 17025943
TI  - Rayleigh's hypothesis and the geometrical optics limit.
AB  - The Rayleigh hypothesis (RH) is often invoked in the theoretical and numerical
      treatment of rough surface scattering in order to decouple the analytical form of
      the scattered field. The hypothesis stipulates that the scattered field away from
      the surface can be extended down onto the rough surface even though it is formed
      by solely up-going waves. Traditionally this hypothesis is systematically used to
      derive the Volterra series under the small perturbation method which is
      equivalent to the low-frequency limit. In this Letter we demonstrate that the RH
      also carries the high-frequency or the geometrical optics limit, at least to
      first order. This finding has never been explicitly derived in the literature.
      Our result comforts the idea that the RH might be an exact solution under some
      constraints in the general case of random rough surfaces and not only in the case
      of small-slope deterministic periodic gratings.

PMID- 17025944
TI  - From Bell's theorem to secure quantum key distribution.
AB  - The first step in any quantum key distribution (QKD) protocol consists of
      sequences of measurements that produce correlated classical data. We show that
      these correlation data must violate some Bell inequality in order to contain
      distillable secrecy, if not they could be produced by quantum measurements
      performed on a separable state of larger dimension. We introduce a new QKD
      protocol and prove its security against any individual attack by an adversary
      only limited by the no-signaling condition.

PMID- 17025945
TI  - Topological defects and the superfluid transition of the s=1 spinor condensate in
      two dimensions.
AB  - The s=1 spinor Bose condensate at zero temperature supports ferromagnetic and
      polar phases that combine magnetic and superfluid ordering. We analyze the
      topological defects of the polar condensate, correcting previous studies, and
      show that the polar condensate in two dimensions is unstable at any finite
      temperature; instead, there is a nematic or paired superfluid phase with
      algebraic order in exp(2itheta), where theta is the superfluid phase, and no
      magnetic order. The Kosterlitz-Thouless transition out of this phase is driven by
      unbinding of half-vortices (the spin-disordered version of the combined spin and
      phase defects found by Zhou), and the anomalous universal 8T(c)/pi stiffness jump
      at the transition is confirmed in numerical simulations. The anomalous stiffness
      jump is a clear experimental signature of this phase and the corresponding phase
      transition.

PMID- 17025946
TI  - Generic phase diagram of Fermion superfluids with population imbalance.
AB  - It is shown by microscopic calculations for trapped imbalanced Fermi superfluids
      that the gap function always has sign changes, i.e., the Fulde-Ferrell-Larkin
      Ovchinnikov (FFLO)-like state, up to a critical imbalance P(c), beyond which
      normal state becomes stable, at temperature T=0. A temperature-versus-pressure
      phase diagram is constructed, where the BCS state without sign change is stable
      only at T not equal to 0. We reproduce the observed bimodality in the density
      profile to identify its origin and evaluate P(c) as functions of T and the
      coupling strength. These dependencies match with the recent experiments.

PMID- 17025947
TI  - Loss tolerance in one-way quantum computation via counterfactual error
      correction.
AB  - We introduce a scheme for fault tolerantly dealing with losses (or other
      "leakage" errors) in cluster state computation that can tolerate up to 50% qubit
      loss. This is achieved passively using an adaptive strategy of measurement--no
      coherent measurements or coherent correction is required. Since the scheme relies
      on inferring information about what would have been the outcome of a measurement
      had one been able to carry it out, we call this counterfactual error correction.

PMID- 17025948
TI  - Generating the curvature perturbation at the end of inflation in string theory.
AB  - In brane inflationary scenarios, the cosmological perturbations are supposed to
      originate from the vacuum fluctuations of the inflaton field corresponding to the
      position of the brane. We show that a significant, and possibly dominant,
      contribution to the curvature perturbation is generated at the end of inflation
      through the vacuum fluctuations of fields, other than the inflaton, which are
      light during the inflationary trajectory and become heavy at the brane-antibrane
      annihilation. These fields appear generically in string compactifications where
      the background geometry has exact or approximate isometries and parametrize the
      internal angular directions of the brane.

PMID- 17025949
TI  - Signatures of the Unruh effect from electrons accelerated by ultrastrong laser
      fields.
AB  - We calculate the radiation resulting from the Unruh effect for strongly
      accelerated electrons and show that the photons are created in pairs whose
      polarizations are perfectly correlated. Apart from the photon statistics, this
      quantum radiation can further be discriminated from the classical (Larmor)
      radiation via the different spectral and angular distributions. The signatures of
      the Unruh effect become significant if the external electromagnetic field
      accelerating the electrons is not too far below the Schwinger limit and might be
      observable with future facilities. Finally, the corrections due to the
      birefringent nature of the QED vacuum at such ultrahigh fields are discussed.

PMID- 17025952
TI  - Negative S parameter from holographic technicolor.
AB  - We present a new class of 5D models, Holographic Technicolor, which fulfills the
      basic requirements for a candidate of comprehensible 4D strong dynamics at the
      electroweak scale. It is the first Technicolor-like model able to provide a
      vanishing or even negative tree-level S parameter, avoiding any no-go theorem on
      its sign. The model is described in the large-N regime. S is therefore
      computable: possible corrections coming from boundary terms follow the 1/N
      suppression, and generation of fermion masses and the S parameter issue do split
      up. We investigate the model's 4D dual, probably walking Technicolor-like with a
      large anomalous dimension.

PMID- 17025950
TI  - Measurements of the branching fractions for psi(3770)-->D(0)D[over ](0), D+D-,
      DD[over ], and the resonance parameters of psi(3770) and psi(2S).
AB  - We measure the branching fractions for psi(3770)-->D(0)D[over ](0), D+D-, DD[over
      ], and non-DD[over ] to be (46.7+/-4.7+/-2.3)%, (36.9+/-3.7+/-2.8)%, (83.6+/
      7.3+/-4.2)%, and (16.4+/-7.3+/-4.2)%, respectively. The resonance parameters of
      psi(3770) and psi(2S) are measured to be M_(psi(3770))=3772.2+/-0.7+/-0.3 MeV,
      Gamma_(psi(3770))(tot)=26.9+/-2.4+/-0.3 MeV, and Gamma_(psi(3770))(ee)=251+/-26+/
      11 eV; M_(psi(2S))=3685.5+/-0.0+/-0.3 MeV, Gamma_(psi(2S))(tot)=331+/-58+/-2 keV,
      and Gamma_(psi(2S))(ee)=2.330+/-0.036+/-0.110 keV. We also measure the light
      hadron R value to be R(uds)=2.262+/-0.054+/-0.109 in the energy region from 3.660
      to 3.872 GeV.

PMID- 17025953
TI  - New critical point induced by the axial anomaly in dense QCD.
AB  - We study the interplay between chiral and diquark condensates within the
      framework of the Ginzburg-Landau free energy, and classify possible phase
      structures of two and three-flavor massless QCD. The QCD axial anomaly acts as an
      external field applied to the chiral condensate in a color superconductor and
      leads to a crossover between the broken chiral symmetry and the color
      superconducting phase, and, in particular, to a new critical point in the QCD
      phase diagram.

PMID- 17025954
TI  - Charm-quark contribution to KL-->mu+mu- at next-to-next-to-leading order.
AB  - We calculate the charm-quark contribution to the decay K(L)-->mu(+)mu(-) in next
      to-next-to-leading order of QCD. This new contribution reduces the theoretical
      uncertainty in the relevant parameter P(c) from +/-22% down to +/-7%,
      corresponding to scale uncertainties of +/-3% and +/-6% in the short-distance
      part of the branching ratio and the determination of the Wolfenstein parameter
      rho[over] from K(L)-->mu(+)mu(-) The error in P(c)=0.115+/-0.018 is now in equal
      shares due to the combined scale uncertainties and the current uncertainty in the
      charm-quark mass. We find B(K(L)-->mu(+)mu(-)) SD=(0.79+/-0.12)x10(-9), with the
      present uncertainty in the Cabibbo-Kobayashi-Maskawa element V(td) being the
      dominant individual source in the quoted error.

PMID- 17025955
TI  - Nonperturbative determination of the QCD potential at O(1/m).
AB  - The relativistic correction to the QCD static interquark potential at O(1/m) is
      investigated nonperturbatively for the first time by using lattice Monte Carlo
      QCD simulations. The correction is found to be comparable with the Coulombic term
      of the static potential when applied to charmonium, and amounts to one-fourth of
      the Coulombic term for bottomonium.

PMID- 17025956
TI  - Magnetic fields boosted by gluon vortices in color superconductivity.
AB  - We investigate the effects of an external magnetic field in the gluon dynamics of
      a color superconductor with three massless quark flavors. In the framework of
      gluon mean-field theory at asymptotic densities, we show that the long-range
      component H[over ] of the external magnetic field that penetrates the color
      flavor locked phase produces an instability when its strength becomes larger than
      the Meissner mass of the charged gluons. As a consequence, the magnetic field
      causes the formation of a vortex state characterized by the condensation of
      charged gluons and the creation of magnetic flux tubes. Inside the flux tubes,
      the magnetic field is stronger than the applied one. This antiscreening effect is
      connected to the anomalous magnetic moment of the gluon field. We suggest how
      this same mechanism could serve to remove the chromomagnetic instabilities
      existing in gapless color superconductivity.

PMID- 17025957
TI  - Anomalous isomeric decays in 174Lu as a probe of K mixing and interactions in
      deformed nuclei.
AB  - A K(pi)=13+, 280 ns four-quasiparticle isomer in the odd-odd nucleus 174Lu has
      been identified and characterized. The isomer decays to both K(pi)=7(+) and
      K(pi)=0(+) rotational bands obtained from the parallel and antiparallel coupling
      of the proton 7/2+[404] and neutron 7/2+[633] orbitals. K mixing caused by
      particle-rotation coupling explains the anomalously fast transition rates to the
      7+ band but those to the 0+ band are caused by a chance degeneracy between the
      isomer and a collective state, allowing the mixing matrix element for a large K
      difference to be deduced.

PMID- 17025958
TI  - Activation measurement of the 3He(alpha,gamma)7Be cross section at low energy.
AB  - The nuclear physics input from the 3He(alpha,gamma)7Be cross section is a major
      uncertainty in the fluxes of 7Be and 8B neutrinos from the Sun predicted by solar
      models and in the 7Li abundance obtained in big-bang nucleosynthesis
      calculations. The present work reports on a new precision experiment using the
      activation technique at energies directly relevant to big-bang nucleosynthesis.
      Previously such low energies had been reached experimentally only by the prompt
      gamma technique and with inferior precision. Using a windowless gas target, high
      beam intensity, and low background gamma-counting facilities, the
      3He(alpha,gamma)7Be cross section has been determined at 127, 148, and 169 keV
      center-of-mass energy with a total uncertainty of 4%. The sources of systematic
      uncertainty are discussed in detail. The present data can be used in big-bang
      nucleosynthesis calculations and to constrain the extrapolation of the
      3He(alpha,gamma)7Be astrophysical S factor to solar energies.

PMID- 17025959
TI  - Time-reversible Born-Oppenheimer molecular dynamics.
AB  - We present a time-reversible Born-Oppenheimer molecular dynamics scheme, based on
      self-consistent Hartree-Fock or density functional theory, where both the nuclear
      and the electronic degrees of freedom are propagated in time. We show how a time
      reversible adiabatic propagation of the electronic degrees of freedom is possible
      despite the nonlinearity and incompleteness of the self-consistent field
      procedure. With a time-reversible lossless propagation the simulated dynamics is
      stabilized with respect to a systematic long-term energy drift and the number of
      self-consistency cycles can be kept low thanks to a good initial guess given from
      the electronic propagation. The proposed molecular dynamics scheme therefore
      combines a low computational cost with a physically correct time-reversible
      representation, which preserves a detailed balance between propagation forwards
      and backwards in time.

PMID- 17025960
TI  - Elliptic and circular dichroism effects in two-photon double ionization of atoms.
AB  - An ab initio parametrization of the two-photon double ionization amplitude from
      an s2 subshell of an atom in a 1S state is presented and used to predict two
      light polarization effects on photoelectron angular distributions that do not
      exist in single-photon double ionization: (i) elliptic dichroism and (ii)
      circular dichroism at equal energy sharing. Estimates for He show large
      magnitudes for these effects, which provide a means for polarization control of
      double ionization by vacuum ultraviolet light.

PMID- 17025961
TI  - High harmonic generation and molecular orbital tomography in multielectron
      systems: beyond the single active electron approximation.
AB  - It was recently shown that the highest molecular orbital of N2 could be
      reconstructed from a series of high harmonic measurements. Existing theories of
      high harmonic generation and orbital tomographic imaging are based on the single
      active electron approximation that ignores essential quantum mechanical
      properties such as the indistinguishability of identical particles and the Pauli
      exclusion principle. We show that, when fully antisymmetrized multielectron wave
      functions and electronic relaxation in the cation are considered, molecular
      orbital tomography records the image of the Dyson orbital plus exchange
      contributions from inner shells. The mixing of contributions from more than one
      molecular orbital gives access to additional wave function information. By
      utilizing the exchange term, harmonic emission from a closed-shell 4-electron
      system can be interpreted as a complete Hartree-Fock wave function.

PMID- 17025962
TI  - Dipolar effect in coherent spin mixing of two atoms in a single optical lattice
      site.
AB  - We show that atomic dipolar effects are detectable in the system that recently
      demonstrated two-atom coherent spin dynamics within individual lattice sites of a
      Mott state. Based on a two-state approximation for the two-atom internal states
      and relying on a variational approach, we have estimated the spin dipolar effect.
      Despite the absolute weakness of the dipole-dipole interaction, it is shown that
      it leads to experimentally observable effects in the spin mixing dynamics.

PMID- 17025963
TI  - Rotational excitation of H2O by cold electrons.
AB  - Experimental data are presented for the scattering of electrons by H2O between 17
      and 250 meV impact energy. These results are used in conjunction with a generally
      applicable method, based on a quantum defect theory approach to electron-polar
      molecule collisions, to derive the first set of data for state-to-state
      rotationally inelastic scattering cross sections based on experimental values.

PMID- 17025964
TI  - Electric dipole moments of water clusters from a beam deflection measurement.
AB  - The response of (H2O)(n=3-18) clusters to an electric field is studied by beam
      deflection. All clusters deflect uniformly, behaving as polarizable particles.
      The effective polarizabilities exceed the electronic component and increase as
      the clusters are cooled, revealing a large permanent dipole contribution. The
      results resolve a discrepancy concerning the polarity of water clusters and show
      that all species access conformations with moments exceeding 1 D. The data show
      no evidence for a freezing transition down to approximately 120 K, but suggest a
      shift in the conformer arrangement at n=8-9.

PMID- 17025965
TI  - High-brightness injection-seeded soft-x-ray-laser amplifier using a solid target.
AB  - We demonstrate the generation of an intense soft-x-ray-laser beam by saturated
      amplification of high harmonic seed pulses in a dense transient collisional soft
      x-ray-laser plasma amplifier created by heating a titanium target. Amplification
      in the 32.6 nm line of Ne-like Ti generates laser pulses of subpicosecond
      duration that are measured to approach full spatial coherence. The peak spectral
      brightness is estimated to be approximately 2 x 10(26) photons/(s mm(2) mrad(2)
      0.01% bandwidth). The scheme is scalable to produce extremely bright lasers at
      very short wavelengths with full temporal and spatial coherence.

PMID- 17025966
TI  - Zero-lag long-range synchronization via dynamical relaying.
AB  - We show that isochronous synchronization between two delay-coupled oscillators
      can be achieved by relaying the dynamics via a third mediating element, which
      surprisingly lags behind the synchronized outer elements. The zero-lag
      synchronization thus obtained is robust over a considerable parameter range. We
      substantiate our claims with experimental and numerical evidence of such
      synchronization solutions in a chain of three coupled semiconductor lasers with
      long interelement coupling delays. The generality of the mechanism is validated
      in a neuronal model with the same coupling architecture. Thus, our results show
      that zero-lag synchronized chaotic dynamical states can occur over long distances
      through relaying, without restriction by the amount of delay.

PMID- 17025967
TI  - Laser beam filamentation in fractal aggregates.
AB  - We investigate filamentation of a cw laser beam in soft matter such as colloidal
      suspensions and fractal gels. The process, driven by electrostriction, is
      strongly affected by material properties, which are taken into account via the
      static structure factor, and have impact on the statistics of the light
      filaments.

PMID- 17025968
TI  - Radiationless traveling waves in saturable nonlinear Schrodinger lattices.
AB  - The long-standing problem of moving discrete solitary waves in nonlinear
      Schrodinger lattices is revisited. The context is photorefractive crystal
      lattices with saturable nonlinearity whose grand-canonical energy barrier
      vanishes for isolated coupling strength values. Genuinely localized traveling
      waves are computed as a function of the system parameters for the first time. The
      relevant solutions exist only for finite velocities.

PMID- 17025969
TI  - Superconducting terminals as sensitive probes for scarred states.
AB  - When a quantum-chaotic normal conductor is coupled to a superconductor, the
      random-matrix theory (RMT) predicts that a gap opens up in the excitation
      spectrum which is of universal size E(g)(RMT) approximately 0.3 Planck/t(D),
      where t(D) is the mean scattering time between Andreev reflections. We show that
      a scarred state of long lifetime t(S)>>t(D) suppresses the excitation gap over a
      window DeltaE approximately 2E(g)(RMT) which can be much larger than the narrow
      resonance width GammaS= Planck/t(S) of the scar in the normal system. The minimal
      value of the excitation gap within this window is given by GammaS/2<<E(g)(RMT).
      Via this suppression of the gap to a nonuniversal value, the scarred state can be
      detected over a much larger energy range than it is in the case when the
      superconducting terminal is replaced by a normal one.

PMID- 17025970
TI  - Quantum reversibility and echoes in interacting systems.
AB  - In echo experiments, imperfect time-reversal operations are performed on a subset
      of the total number of degrees of freedom. To capture the physics of these
      experiments, we introduce a partial fidelity M(B)(t), the Boltzmann echo, where
      only part of the system's degrees of freedom can be time reversed. We present a
      semiclassical calculation of M(B)(t). We show that, as the time-reversal
      operation is performed more and more accurately, the decay rate of M(B)(t)
      saturates at a value given by the decoherence rate of the controlled degrees of
      freedom due to their coupling to uncontrolled ones. We connect these results with
      NMR spin echo experiments.

PMID- 17025971
TI  - Observation of surface-avoiding waves: a new class of extended states in periodic
      media.
AB  - Coherent time-domain optical experiments on GaAs-AlAs superlattices reveal the
      existence of an unusually long-lived acoustic mode at approximately 0.6 THz which
      couples weakly to the environment by evading the sample boundaries. Classical as
      well as quantum states that steer clear of surfaces are generally shown to occur
      in the spectrum of periodic structures, for most boundary conditions. These
      surface-avoiding waves are associated with frequencies outside forbidden gaps and
      wave vectors in the vicinity of the center and edge of the Brillouin zone.
      Possible consequences for surface science and resonant-cavity applications are
      discussed.

PMID- 17025951
TI  - Search for neutral Higgs bosons decaying to tau pairs in pp[over ] collisions at
      sqrt[s]=1.96 TeV.
AB  - A search for the production of neutral Higgs bosons Phi decaying into tau(+)tau(
      ) final states in pp[over ] collisions at a center-of-mass energy of 1.96 TeV is
      presented. The data, corresponding to an integrated luminosity of approximately
      325 pb(-1), were collected by the D0 experiment at the Fermilab Tevatron
      Collider. Since no excess compared to the expectation from standard model
      processes is found, limits on the production cross section times branching ratio
      are set. The results are combined with those obtained from the D0 search for
      Phib(b[over ])-->bb[over ]b(b[over ]) and are interpreted in the minimal
      supersymmetric standard model.

PMID- 17025972
TI  - Asymmetric heat conduction in nonlinear lattices.
AB  - In this Letter, we conduct an extensive study of the two-segment Frenkel
      Kontorova model. We show that the rectification effect of the heat flux reported
      in recent literature is possible only in the weak interfacial coupling limit. The
      rectification effect will be reversed when the properties of the interface and
      the system size change. These two types of asymmetric heat conduction are
      governed by different mechanisms though both are induced by nonlinearity. An
      intuitive physical picture is proposed to interpret the reversal of the
      rectification effect. Since asymmetric heat conduction depends critically on the
      properties of the interface and the system size, it is probably not an easy task
      to fabricate a thermal rectifier or thermal diode in practice.

PMID- 17025973
TI  - Quasicrystalline and rational approximant wave patterns in hydrodynamic and
      quantum nested wells.
AB  - The eigenfunctions of nested wells with an incommensurate boundary geometry, in
      both the hydrodynamic shallow water regime and quantum cases, are systematically
      and exhaustively studied in this Letter. The boundary arrangement of the nested
      wells consists of polygonal ones, square or hexagonal, with a concentric
      immersed, similar but rotated, well or plateau. A rich taxonomy of wave patterns,
      such as quasicrystalline states, their crystalline rational approximants, and
      some other exotic but well known tilings, is found in these mimicked experiments.
      To the best of our knowledge, these hydrodynamic rational approximants are
      presented here for the first time in a hydrodynamic-quantum framework. The
      corresponding statistical nature of the energy level spacing distribution
      reflects this taxonomy by changing the spectral types.

PMID- 17025974
TI  - Geometry of intensive scalar dissipation events in turbulence.
AB  - The maxima of the scalar dissipation rate in turbulence appear in the form of
      sheets and correspond to the potentially most intensive scalar mixing events.
      Their cross section extension determines a locally varying diffusion scale of the
      mixing process and extends the classical Batchelor picture of one mean diffusion
      scale. The distribution of the local diffusion scales is analyzed for different
      Reynolds and Schmidt numbers with a fast multiscale technique applied to very
      high-resolution simulation data. The scales always take values across the whole
      Batchelor range and beyond. Furthermore, their distribution is traced back to the
      distribution of the contractive short-time Lyapunov exponent of the flow.

PMID- 17025975
TI  - Dynamics of mass transport and magnetic fields in low-wire-number-array Z
      pinches.
AB  - The dynamics of mass transport were observed in a wire array implosion with
      multiframe laser probing. Plasma bubbles arise at breaks in the wires.
      Interferometry shows that the leading edge of the bubbles brings material to the
      axis of the array. The speed of this material was measured to be > or =3 x 10(7)
      cm/s during the wire array implosion. A shock was observed during the collision
      of the bubbles with the precursor. The Faraday effect indicates current flowing
      in breaks on the wires. The current switches from the imploding mass to the on
      axis plasma column at the beginning of the x-ray pulse.

PMID- 17025976
TI  - Detection of zero-mean-frequency zonal flows in the core of a high-temperature
      tokamak plasma.
AB  - A low-frequency, spectrally broad (Deltaf approximately 10 kHz) poloidal flow
      structure that peaks near zero frequency is observed in time-resolved
      measurements of the turbulence velocity field in the core region (r/a
      approximately 0.6-0.9) of DIII-D tokamak plasmas. These flows exhibit a long
      poloidal wavelength (low m) and a short radial coherence length comparable to the
      ambient turbulence decorrelation length. Characteristics of these observed
      poloidal flows are consistent with the theoretically predicted residual or zero
      mean-frequency zonal flows.

PMID- 17025977
TI  - Spinodal decomposition in solid isotopic helium mixtures.
AB  - We report the first observations of spinodal decomposition in solid helium
      isotopic mixtures, using NMR measurements. The experiments were performed at a
      3He concentration of 50% where the transition proceeds through the critical
      point. We used an initial pressure such that the system remained solid. Our
      observations indicate that the transition occurs by the mechanism of spinodal
      decomposition and we are able to study its evolution in real time.

PMID- 17025978
TI  - Ginzburg-Landau theory of a supersolid.
AB  - We develop a simple Ginsburg-Landau theory to study all the possible phases and
      phase transitions in 4He, analyze the condition for the existence of the
      supersolid (SS) and map out its global phase diagram from a unified framework. If
      the condition favors the existence of the SS, we use the GL theory to address
      several experimental facts and also make some predictions that are amenable to
      experimental tests. A key prediction is that the x-ray scattering intensity from
      the SS ought to have an additional modulation over that of the normal solid. The
      modulation amplitude is proportional to the nonclassical rotational-inertial
      observed in the torsional oscillator experiments.

PMID- 17025979
TI  - Low self-affine exponents of fractured glass ceramics surfaces.
AB  - The geometry of postmortem rough fracture surfaces of porous glass ceramics made
      of sintered glass beads is shown experimentally to be self-affine with an
      exponent zeta=0.40+/-0.04, remarkably lower than the "universal" value zeta=0.8
      frequently measured for many materials. This low value of zeta is similar to that
      found for sandstone samples of similar microstructure and is also practically
      independent on the porosity phi in the range investigated (3%< or =phi< or =26%)
      as well as on the bead diameter d and of the crack growth velocity. In contrast,
      the roughness amplitude normalized by d increases linearly with phi while it is
      still independent, within experimental error, of d and of the crack propagation
      velocity. An interpretation of this variation is suggested in terms of a
      transition from transgranular to intergranular fracture propagation with no
      influence, however, on the exponent zeta.

PMID- 17025980
TI  - Temperature-driven change in the unstable growth mode on patterned GaAs(001).
AB  - We observe a dramatic change in the unstable growth mode during GaAs molecular
      beam epitaxy on patterned GaAs(001) as the temperature is lowered through
      approximately 540 degrees C, roughly coincident with the preroughening
      temperature. Observations of the As2 flux dependence, however, rule out
      thermodynamic preroughening as driving the growth mode change. Similar
      observations rule out the change in surface reconstruction as the cause. Instead,
      we find evidence that the change in the unstable growth mode can be explained by
      a competition between the decreased adatom collection rate on small terraces and
      a small anisotropic barrier to adatom diffusion downward across step bunches.

PMID- 17025981
TI  - Chemical reactivity of Ni-Rh nanowires.
AB  - The properties of bimetallic Ni-Rh nanowires, fabricated by decorating the steps
      of vicinal Rh(111) surfaces by stripes of self-assembled Ni adatoms, have been
      probed by STM, photoemission, and ab initio density functional theory
      calculations. These Ni-Rh nanowires have specific electronic properties that lead
      to a significantly enhanced chemical reactivity towards oxygen. As a result, the
      Ni-Rh nanowires can be oxidized exclusively, generating novel quasi-one
      dimensional oxide structures.

PMID- 17025982
TI  - Generalized electron counting in determination of metal-induced reconstruction of
      compound semiconductor surfaces.
AB  - Based on theoretical analysis, first-principles calculations, and experimental
      observations, we establish a generic guiding principle, embodied in generalized
      electron counting (GEC), that governs the surface reconstruction of compound
      semiconductors induced by different metal adsorbates. Within the GEC model, the
      adsorbates serve as an electron bath, donating or accepting the right number of
      electrons as the host surface chooses a specific reconstruction that obeys the
      classic electron-counting model. The predictive power of the GEC model is
      illustrated for a wide range of metal adsorbates.

PMID- 17025983
TI  - Real-time ab initio simulations of excited carrier dynamics in carbon nanotubes.
AB  - Combining time-dependent density functional calculations for electrons with
      molecular dynamics simulations for ions, we investigate the dynamics of excited
      carriers in a (3,3) carbon nanotube at different temperatures. Following an
      hnu=6.8 eV photoexcitation, the carrier decay is initially dominated by efficient
      coupling to electronic degrees of freedom. At room temperature, the excitation
      gap is reduced to nearly half its initial value after approximately 230 fs, where
      coupling to ionic motion starts dominating the decay. We show that the onset
      point and damping rate in the phonon regime change with initial ion velocities, a
      manifestation of temperature-dependent coupling between electronic and ionic
      degrees of freedom.

PMID- 17025984
TI  - Kinetic-anisotropy-induced ordering-orientation transition in epitaxial growth: a
      method to synthesize ordering-orientation superlattices.
AB  - The epitaxial growth has a distinct kinetic feature that the lateral surface
      diffusion is faster than the longitudinal bulk diffusion. We show there is an
      ordering-orientation transition of alloy films with the change of growth rate due
      to this kinetic anisotropy. As an example, we have calculated the epitaxial
      growth of CoPt alloy films on the Pt buffer layer. We show the ordered structure
      of CoPt films changes from the L1(0) [001] (a compositional modulation along the
      [001] direction) variant to the L1(0) [100] variant with the increase of growth
      rate. This ordering-orientation transition also occurs with the decrease of
      temperature at adequate growth rate. Based on this mechanism, we propose a simple
      method to synthesize the ordering-orientation superlattices.

PMID- 17025985
TI  - Surface structure of an ultrathin alumina film on Ni3Al(111): a dynamic scanning
      force microscopy study.
AB  - The surface structure of an ultrathin alumina film on a Ni3Al(111) substrate has
      been studied by dynamic scanning force microscopy. The alumina film exhibits a
      hexagonal superstructure with a lattice parameter of 4.14 nm and a (1/sqrt[3] x
      1/sqrt[3])R30 degrees substructure. Two domains rotated by 24 degrees are
      present. The film is terminated by a hexagonal lattice of oxygen ions with a
      lattice parameter of 0.293 nm, which is rotated by 30 degrees with respect to the
      substrate lattice. The nodes of the 4.14 nm superstructure and the 2.39 nm
      substructure are pinned on points of the substrate lattice, where the surface
      atomic lattice is almost commensurable. The oxygen lattice is perfectly hexagonal
      close to these nodes and disordered in the surrounding regions.

PMID- 17025986
TI  - Shubnikov-de Haas effect in the metallic state of Na0.3CoO2.
AB  - Shubnikov-de Haas oscillations for two well-defined frequencies, corresponding,
      respectively, to areas of 0.8 and 1.36% of the first Brillouin zone, were
      observed in single crystals of Na(0.3)CoO2. The existence of Na superstructures
      in Na0.3CoO2, coupled with this observation, suggests the possibility that the
      periods are due to the reconstruction of the large Fermi surface around the Gamma
      point. An alternative interpretation in terms of the long sought-after
      epsilon'(g) pockets is also considered but found to be incompatible with existing
      specific heat data.

PMID- 17025987
TI  - Berry-phase oscillations of the Kondo effect in single-molecule magnets.
AB  - We show that it is possible to topologically induce or quench the Kondo resonance
      in the conductance of a single-molecule magnet (S>1/2) strongly coupled to
      metallic leads. This can be achieved by applying a magnetic field perpendicular
      to the molecule easy axis and works for both full- and half-integer spin cases.
      The effect is caused by the Berry-phase interference between two quantum
      tunneling paths of the molecule's spin. We have calculated the renormalized Berry
      phase oscillations of the Kondo peaks as a function of the transverse magnetic
      field as well as the conductance of the molecule by means of the poor man's
      scaling method. We propose to use a new variety of the single-molecule magnet Ni4
      for the experimental observation of this phenomenon.

PMID- 17025988
TI  - Intrinsic versus extrinsic anomalous Hall effect in ferromagnets.
AB  - A unified theory of the anomalous Hall effect (AHE) is presented for multiband
      ferromagnetic metals with dilute impurities. In the clean limit, the AHE is
      mostly due to extrinsic skew scattering. When the Fermi level is located around
      anticrossing of band dispersions split by spin-orbit interaction, the intrinsic
      AHE to be calculated ab initio is resonantly enhanced by its nonperturbative
      nature, revealing the extrinsic-to-intrinsic crossover which occurs when the
      relaxation rate is comparable to the spin-orbit coupling.

PMID- 17025989
TI  - Current-induced polarization and the spin Hall effect at room temperature.
AB  - Electrically induced electron spin polarization is imaged in n-type ZnSe
      epilayers using Kerr rotation spectroscopy. Despite no evidence for an
      electrically induced internal magnetic field, current-induced in-plane spin
      polarization is observed with characteristic spin lifetimes that decrease with
      doping density. The spin Hall effect is also observed, indicated by an
      electrically induced out-of-plane spin polarization with opposite sign for spins
      accumulating on opposite edges of the sample. The spin Hall conductivity is
      estimated as 3+/-1.5 Omega(-1) m(-1)/|e| at 20 K, which is consistent with the
      extrinsic mechanism. Both the current-induced spin polarization and the spin Hall
      effect are observed at temperatures from 10 to 295 K.

PMID- 17025990
TI  - Fractional quantum Hall States of Dirac electrons in graphene.
AB  - We have investigated the fractional quantum Hall states of Dirac electrons in a
      graphene layer in different Landau levels. The relativistic nature of the energy
      dispersion relation of electrons in graphene significantly modifies the
      interelectron interactions. This results in a specific dependence of the ground
      state energy and the energy gaps for electrons on the Landau-level index. For the
      valley-polarized states, i.e., at nu=1/m, m being an odd integer, the energy gaps
      have the largest values in the n=1 Landau level. For the valley-unpolarized
      states, e.g., for the 2/3 state, the energy gaps are suppressed for n=1 as
      compared to those at n=0. For both n=1 and n=0, the ground state of the 2/3
      system is fully valley-unpolarized.

PMID- 17025991
TI  - Field dependent coherence length in the superclean, high-kappa superconductor
      CeCoIn5.
AB  - Using small-angle neutron scattering, we have studied the flux-line lattice (FLL)
      in the superclean, high-kappa superconductor CeCoIn5. The FLL undergoes a first
      order symmetry and reorientation transition at approximately 0.55 T at 50 mK. In
      addition, the FLL form factor in this material is found to be independent of the
      applied magnetic field, in striking contrast to the exponential decrease usually
      observed in superconductors. This result is consistent with a strongly field
      dependent coherence length, proportional to the vortex separation.

PMID- 17025992
TI  - Phase diagram of the disordered RKKY model in dilute magnetic semiconductors.
AB  - We consider ferromagnetism in spatially randomly located magnetic moments, as in
      a diluted magnetic semiconductor, coupled via the carrier-mediated indirect
      exchange RKKY interaction. We obtain, via Monte Carlo calculations, the magnetic
      phase diagram as a function of the impurity moment density n(i) and the relative
      carrier concentration n(c)/n(i). As evidenced by the diverging correlation length
      and magnetic susceptibility, the boundary between ferromagnetic and
      nonferromagnetic phases constitutes a line of zero temperature critical points
      which can be viewed as a magnetic percolation transition. In the dilute limit, we
      find that bulk ferromagnetism vanishes for n(c)/n(i) >0.1. We also incorporate
      the local antiferromagnetic direct superexchange interaction between nearest
      neighbor impurities and examine the impact of a damping factor in the RKKY range
      function.

PMID- 17025993
TI  - Anisotropic magnetoresistance and anisotropic tunneling magnetoresistance due to
      quantum interference in ferromagnetic metal break junctions.
AB  - We measure the low-temperature resistance of permalloy break junctions as a
      function of contact size and the magnetic field angle in applied fields large
      enough to saturate the magnetization. For both nanometer-scale metallic contacts
      and tunneling devices we observe large changes in resistance with the angle, as
      large as 25% in the tunneling regime. The pattern of magnetoresistance is
      sensitive to changes in bias on a scale of a few mV. We interpret the effect as a
      consequence of conductance fluctuations due to quantum interference.

PMID- 17025994
TI  - Domain state and exchange coupling in MnPt with Co clusters.
AB  - This Letter reports on the exchange coupling between nanometric Co clusters and
      disordered MnPt thin films. It is found that, under field-cooling, the MnPt
      develops a bulk magnetization M_{AF}. The correlation between M_{AF} and the
      exchange bias H_{b} is studied using a different field-cooling procedure. From
      this, using a mean-field approach, it is shown that the effective field acting on
      the interface magnetization responsible for H_{b} is proportional to M_{AF}. This
      results is strong evidence in favor of the domain state model for exchange bias,
      in which H_{b} is correlated with the bulk magnetic state of the antiferromagnet,
      and not only restricted to its interface configuration.

PMID- 17025995
TI  - Supersolid phase in spin dimer XXZ systems under a magnetic field.
AB  - Using the quantum Monte Carlo method, we study, under external magnetic fields,
      the ground state phase diagram of the two-dimensional spin S=1/2 dimer model with
      an anisotropic intraplane antiferromagnetic coupling. With the anisotropy 4
      greater/approximately Delta greater/approximately 3, a supersolid phase
      characterized by a nonuniform Bose condensate density that breaks translational
      symmetry is found. The rich phase diagram also contains a checkerboard solid, an
      antiferromagnet in the z axis, and a superfluid phase formed by S(z)= +1 spin
      triplets which has a finite staggered magnetization in the in-plane direction. As
      we show, the model can be realized as a consequence of including the next nearest
      neighbor coupling among dimers and our results suggest that spin dimer systems
      may be an ideal model system to study the supersolid phase.

PMID- 17025996
TI  - Quasiuniform in-plane magnetization state of thin cylindrical dots in a square
      array and related anisotropy.
AB  - The energy (magnetostatic, exchange, and Zeeman terms) of a square array of
      cylindrical submicron dots made of soft ferromagnetic material is calculated
      analytically and minimized, taking into account the quasiuniformity of dot
      magnetization. The dependence of the equilibrium energy of the array on the
      direction of the externally applied magnetic field in the array plane is
      recovered, exhibiting the fourfold anisotropy. The anisotropy constant is
      calculated. Its values for different array geometries are in excellent agreement
      with the recent independent experiments. A new eightfold anisotropy effect is
      predicted. The theory involves no adjustable parameters.

PMID- 17025997
TI  - Damped precession of the magnetization vector of superparamagnetic nanoparticles
      excited by femtosecond optical pulses.
AB  - The ultrafast magnetization and electron dynamics of superparamagnetic cobalt
      nanoparticles, embedded in a dielectric matrix, have been investigated using
      femtosecond optical pulses. Our experimental approach allows us to bypass the
      superparamagnetic thermal fluctuations and to observe the trajectory of the
      magnetization vector which exhibits a strongly damped precession motion. The
      magnetization precession is damped faster in the superparamagnetic particles than
      in cobalt films or when the particle size decreases, suggesting that the damping
      is enhanced at the metal dielectric interface. Our observations question the
      gyroscopic nature of the magnetization pathway when superparamagnetic
      fluctuations take place as we discuss in the context of Brown's model.

PMID- 17025998
TI  - Colloidal aggregation in a nematic liquid crystal: topological arrest of
      particles by a single-stroke disclination line.
AB  - We numerically study many-body interactions among colloidal particles suspended
      in a nematic liquid crystal, using a fluid particle dynamics method, which
      properly incorporates dynamical coupling among particles, nematic orientation,
      and flow field. Based on simulation results, we propose a new type of
      interparticle interaction in addition to well-known quadrupolar interaction for
      particles accompanying Saturn-ring defects. This interaction is mediated by the
      defect of the nematic phase: upon nematic ordering, a closed disclination loop
      binds more than two particles to form a sheetlike dynamically arrested structure.
      The interaction depends upon the topology of a disclination loop binding
      particles, which is determined by aggregation history.

PMID- 17025999
TI  - Regular surface patterns on Rayleigh-Taylor unstable evaporating films heated
      from below.
AB  - We study a thin liquid film with a free surface on the underside of a cooled
      horizontal substrate. We show that if the fluid is initially in equilibrium with
      its own vapor in the gas phase below, regular surface patterns in the form of
      long-wave hexagons having a well-defined lateral length scale are observed. This
      is in sharp contrast to the case without evaporation where rupture or coarsening
      to larger and larger patterns is seen in the long time limit. In this way,
      evaporation could be used for regular structuring of the film surface. Finally,
      we estimate the finite wave length for the simplified case of an extended Cahn
      Hilliard equation.

PMID- 17026000
TI  - Coarse-grained lattice model for molecular recognition.
AB  - We present a simple model which allows us to investigate the equilibrium aspects
      of molecular recognition between rigid biomolecules on a generic level. Using a
      two-stage approach, which consists of a design and a testing step, the role of
      cooperativity and of varying bond strength in molecular recognition is
      investigated. Cooperativity is found to enhance selectivity. In complexes which
      require a high binding flexibility, a small number of strong bonds seems to be
      favored compared to a situation with many but weak bonds.

PMID- 17026001
TI  - Chromosome oscillations in mitosis.
AB  - The motion and positioning of chromosomes during eukaryotic cell division is
      investigated theoretically. We perform a self-contained analysis where the motion
      of mono-oriented chromosomes results from the competition between the kinetochore
      and chromokinesin motors on the chromosome arms. We show that the interplay
      between the asterlike morphology of the mitotic spindle and the collective
      dynamics of motors accounts for chromosome motion, positioning, and congression.
      In particular, the characteristic oscillations of chromosomes observed in vivo
      arise naturally within this description.

PMID- 17026002
TI  - Active elasticity of gels with contractile cells.
AB  - Cells play an active role in the maintenance of mechanical homeostasis within
      tissues and their response to elastic forces is important for tissue engineering.
      We predict the collective response of an ensemble of contractile cells in a three
      dimensional elastic medium to externally applied strain fields. Motivated by
      experiment, we model the cells as polarizable force dipoles that change their
      orientation in response to the local elastic strain. The analogy between the
      mechanical response of these systems and the dielectric response of polar
      molecules is used to calculate the elastic response function. We use this analogy
      to evaluate the average cell orientation, the mean polarization stress, and the
      effective elastic constants of the material, as a function of the cell
      concentration and matrix properties.

PMID- 17026003
TI  - Self-energy-limited ion transport in subnanometer channels.
AB  - The current-voltage characteristics of the alpha-Hemolysin protein pore during
      the passage of single-stranded DNA under varying ionic strength C are studied
      experimentally. We observe strong blockage of the current, weak superlinear
      growth of the current as a function of voltage, and a minimum of the current as a
      function of C. These observations are interpreted as the result of the ion
      electrostatic self-energy barrier originating from the large difference in the
      dielectric constants of water and the lipid bilayer. The dependence of DNA
      capture rate on C also agrees with our model.

PMID- 17026004
TI  - Sequence sensitivity of breathing dynamics in heteropolymer DNA.
AB  - We study the fluctuation dynamics of localized denaturation bubbles in
      heteropolymer DNA with a master equation and complementary stochastic simulation
      based on novel DNA stability data. A significant dependence of opening
      probability and waiting time between bubble events on the local DNA sequence is
      revealed and quantified for a biological sequence of the T7 bacteriophage.
      Quantitative agreement with data from fluorescence correlation spectroscopy is
      demonstrated.

PMID- 17026005
TI  - Semiflexible polymers in shear flow.
AB  - The dynamics of semiflexible polymers under the influence of shear flow is
      studied analytically. Power laws are derived for various conformational and
      dynamical quantities which are in agreement with experimental findings. In
      particular, the tumbling motion is analyzed and expressions are provided for the
      probability distributions of the orientation angles and the tumbling time. The
      calculations explain the similarities in the behavior of flexible and
      semiflexible polymers as well as free-draining and nondraining systems.

PMID- 17026006
TI  - Statistical mechanics of combinatorial auctions.
AB  - Combinatorial auctions are formulated as frustrated lattice gases on sparse
      random graphs, allowing the determination of the optimal revenue by methods of
      statistical physics. Transitions between computationally easy and hard regimes
      are found and interpreted in terms of the geometric structure of the space of
      solutions. We introduce an iterative algorithm to solve intermediate and large
      instances, and discuss competing states of optimal revenue and maximal number of
      satisfied bidders. The algorithm can be generalized to the hard phase and to more
      sophisticated auction protocols.

PMID- 17026007
TI  - Localized chemical wave emission and mode switching in a patterned excitable
      medium.
AB  - Chemical waves are initiated from complex geometries in the excitable Belosouv
      Zhabotinsky medium using a wet stamping technique. Because of the coupling
      between the system's chemical kinetics and geometry, waves are emitted only from
      selected locations. By varying the nature of the wave-triggering reagent (here
      formaldehyde or methanol), it is possible to switch between two spatially
      distinct modes of wave emission. The system's dynamics is studied numerically,
      and the results of modeling agree with experimental observations.

PMID- 17026008
TI  - Comment I on "Inconsistency in the application of the adiabatic theorem".

PMID- 17026009
TI  - Comment II on "Inconsistency in the application of the adiabatic theorem".

PMID- 17026011
TI  - Biased diffusion and universality in model queues.
AB  - We study the structure and robustness of universality classes for queueing,
      deriving analytic results for priority-based models with continuous-valued
      priorities. By mapping one model onto the problem of biased diffusion, we show
      that its distribution of waiting times, P(tau), decreases for large times tau as
      P(tau) approximately tau;{-3/2} or as P(tau) approximately tau;{-5/2}exp(
      tau/tau_{0}) in different parameter regimes. In a second model, introducing a
      cost for switching between different classes of tasks substantially changes the
      asymptotic behavior of P(tau).

PMID- 17026012
TI  - Hamiltonian approach to the dynamical Casimir effect.
AB  - A Hamiltonian approach is introduced in order to address some severe problems
      associated with the physical description of the dynamical Casimir effect at all
      times. For simplicity, the case of a neutral scalar field in a one-dimensional
      cavity with partially transmitting mirrors (an essential proviso) is considered,
      but the method can be extended to fields of any kind and higher dimensions. The
      motional force calculated in our approach contains a reactive term-proportional
      to the mirrors' acceleration--which is fundamental in order to obtain
      (quasi)particles with a positive energy all the time during the movement of the
      mirrors--while always satisfying the energy conservation law. Comparisons with
      other approaches and a careful analysis of the interrelations among the different
      results previously obtained in the literature are carried out.

PMID- 17026013
TI  - Zeno and anti-Zeno effects for quantum Brownian motion.
AB  - In this Letter, we investigate the occurrence of the Zeno and anti-Zeno effects
      for quantum Brownian motion. We single out the parameters of both the system and
      the reservoir governing the crossover between Zeno and anti-Zeno dynamics. We
      demonstrate that, for high reservoir temperatures, the short time behavior of
      environment induced decoherence is ultimately responsible for the occurrence of
      either the Zeno or the anti-Zeno effect. Finally, we suggest a way to manipulate
      the decay rate of the system and to observe a controlled continuous passage from
      decay suppression to decay acceleration using engineered reservoirs in the
      trapped ion context.

PMID- 17026014
TI  - Projections of quantum observables onto classical degrees of freedom in mixed
      quantum-classical simulations: understanding linear response failure for the
      photoexcited hydrated electron.
AB  - We present a general analytic method for understanding how specific motions of a
      classical bath influence the dynamics of quantum-mechanical observables in mixed
      quantum-classical molecular dynamics simulations. We apply our method and develop
      expressions for the special case of quantum solvation, allowing us to examine how
      specific classical solvent motions couple to the equilibrium energy fluctuations
      and nonequilibrium energy relaxation of a quantum-mechanical solute. As a first
      application of our formalism, we investigate the motions of classical water
      underlying the equilibrium and nonequilibrium excited-state solvent response
      functions of the hydrated electron; the results allow us to explain why the
      linear response approximation fails for this system.

PMID- 17026015
TI  - Spontaneous circulation in ground-state spinor dipolar Bose-Einstein condensates.
AB  - We report on a study of the spin-1 ferromagnetic Bose-Einstein condensate with
      magnetic dipole-dipole interactions. By solving the nonlocal Gross-Pitaevskii
      equations for this system, we find three ground-state phases. Moreover, we show
      that a substantial orbital angular momentum accompanied by chiral symmetry
      breaking emerges spontaneously in a certain parameter regime. We predict that all
      these phases can be observed in the spin-1 87Rb condensate by changing the number
      of atoms or the trap frequency.

PMID- 17026016
TI  - Separable measurement estimation of density matrices and its fidelity gap with
      collective protocols.
AB  - We show that there exists a gap between the performance of separable and
      collective measurements in the qubit mixed-state estimation that persists in the
      large sample limit. We characterize the gap with sharp asymptotic bounds on mean
      fidelity. We present an adaptive protocol that attains the separable measurement
      bound. This protocol uses von Neumann measurements and can be easily implemented
      with current technology.

PMID- 17026017
TI  - Generic entanglement and standard form for N-mode pure Gaussian states.
AB  - We investigate the correlation structure of pure N-mode Gaussian resources which
      can be experimentally generated by means of squeezers and beam splitters, whose
      entanglement properties are generic. We show that those states are specified (up
      to local unitaries) by N(N-1)/2 parameters, corresponding to the two-point
      correlations between any pair of modes. Our construction yields a practical
      scheme to engineer such generic-entangled N-mode pure Gaussian states by linear
      optics. We discuss our findings in the framework of Gaussian matrix product
      states of harmonic lattices, raising connections with entanglement frustration
      and the entropic area law.

PMID- 17026018
TI  - Quantum pattern retrieval by qubit networks with Hebb interactions.
AB  - Qubit networks with long-range interactions inspired by the Hebb rule can be used
      as quantum associative memories. Starting from a uniform superposition, the
      unitary evolution generated by these interactions drives the network through a
      quantum phase transition at a critical computation time, after which
      ferromagnetic order guarantees that a measurement retrieves the stored pattern.
      The maximum memory capacity of these qubit networks is reached at a memory
      density alpha=p/n=1.

PMID- 17026019
TI  - Accurate optical lattice clock with 87Sr atoms.
AB  - We report a frequency measurement of the 1S0-3P0 transition of 87Sr atoms in an
      optical lattice clock. The frequency is determined to be 429 228 004 229 879(5)
      Hz with a fractional uncertainty that is comparable to state-of-the-art optical
      clocks with neutral atoms in free fall. The two previous measurements of this
      transition were found to disagree by about 2 x 10(-13), i.e., almost 4 times the
      combined error bar and 4 to 5 orders of magnitude larger than the claimed
      ultimate accuracy of this new type of clocks. Our measurement is in agreement
      with one of these two values and essentially resolves this discrepancy.

PMID- 17026020
TI  - Codimension-two critical behavior in vacuum gravitational collapse.
AB  - We consider the critical behavior at the threshold of black-hole formation for
      the five-dimensional vacuum Einstein equations satisfying the cohomogeneity-two
      triaxial Bianchi type-IX ansatz. Exploiting a discrete symmetry present in this
      model we predict the existence of a codimension-two attractor. This prediction is
      confirmed numerically and the codimension-two attractor is identified as a
      discretely self-similar solution with two unstable modes.

PMID- 17026021
TI  - Constraining a possible time variation of the gravitational constant through
      "gravitochemical heating" of neutron stars.
AB  - A hypothetical time variation of the gravitational constant G would cause neutron
      star matter to depart from beta equilibrium, due to the changing hydrostatic
      equilibrium. This induces nonequilibrium beta processes, which release energy
      that is invested partly in neutrino emission and partly in internal heating.
      Eventually, the star arrives at a stationary state in which the temperature
      remains nearly constant, as the forcing through the change of G is balanced by
      the ongoing reactions. Using the surface temperature of the nearest millisecond
      pulsar, PSR J0437-4715, inferred from ultraviolet observations, we estimate two
      upper limits for this variation: (1) |.G/G|< 2 x 10(-10) yr(-1), if direct Urca
      reactions are allowed, and (2) |.G/G|< 4 x 10(-12) yr(-1), considering only
      modified Urca reactions. The latter is among the most restrictive obtained by
      other methods.

PMID- 17026022
TI  - Postsphaleron baryogenesis.
AB  - We present a new mechanism for generating the baryon asymmetry of the Universe
      directly in the decay of a singlet scalar field S(r) with a weak scale mass and a
      high dimensional baryon number-violating coupling. Unlike most currently popular
      models, this mechanism, which becomes effective after the electroweak phase
      transition, does not rely on the sphalerons for inducing a nonzero baryon number.
      CP asymmetry in S(r) decay arises through loop diagrams involving the exchange of
      W+/- gauge bosons and is suppressed by light quark masses, leading naturally to a
      value of eta(B) approximately 10(-10). The simplest realization of this idea
      which uses a six quark DeltaB=2 operator predicts colored scalars accessible to
      the CERN Large Hadron Collider and neutron-antineutron oscillation within reach
      of the next-generation experiments.

PMID- 17026023
TI  - Ellipsoidal universe can solve the cosmic microwave background quadrupole
      problem.
AB  - The recent 3 yr Wilkinson Microwave Anisotropy Probe data have confirmed the
      anomaly concerning the low quadrupole amplitude compared to the best-fit Lambda
      cold dark matter prediction. We show that by allowing the large-scale spatial
      geometry of our universe to be plane symmetric with eccentricity at decoupling or
      order 10(-2), the quadrupole amplitude can be drastically reduced without
      affecting higher multipoles of the angular power spectrum of the temperature
      anisotropy.

PMID- 17026024
TI  - Galilean equivalence for galactic dark matter.
AB  - Satellite galaxies are tidally disrupted as they orbit the Milky Way. If dark
      matter (DM) experiences a stronger self-attraction than baryons, stars will
      preferentially gain rather than lose energy during tidal disruption, leading to
      an enhancement in the trailing compared to the leading tidal stream. The Sgr
      dwarf galaxy is seen to have roughly equal streams, challenging models in which
      DM and baryons accelerate differently by more than 10%. Future observations and a
      better understanding of DM distribution should allow detection of equivalence
      violation at the percent level.

PMID- 17026025
TI  - Improved experimental limit on the electric dipole moment of the neutron.
AB  - An experimental search for an electric dipole moment (EDM) of the neutron has
      been carried out at the Institut Laue-Langevin, Grenoble. Spurious signals from
      magnetic-field fluctuations were reduced to insignificance by the use of a
      cohabiting atomic-mercury magnetometer. Systematic uncertainties, including
      geometric-phase-induced false EDMs, have been carefully studied. The results may
      be interpreted as an upper limit on the neutron EDM of |d(n)|< 2.9 x 10(-26)e cm
      (90% C.L.).

PMID- 17026026
TI  - Has new physics already been seen in B(d) meson decays?
AB  - We show in a model independent way that, within the standard model, the deviation
      in the measured B(d){0}-B[over](d){0} mixing phase caused by pollution from
      another amplitude is always less in magnitude, and has the same sign as, the weak
      phase of the polluting amplitude. The exception is to have large destructive
      interference between the two amplitudes: any deviation larger than a few degrees
      is only possible if the observed decay rate results from fine-tuned cancellations
      between significantly larger amplitudes. This is unlikely given our understanding
      of B decays. Even if the deviation reduces to a few degrees in the future, new
      physics would still likely be implied.

PMID- 17026029
TI  - Isotope shift of the 32S 1/2 -22S 1/2 transition in lithium and the nuclear
      polarizability.
AB  - High precision calculation of the isotope shift of the 3(2)S(1/2)-2(2)S(1/2)
      transition in lithium is presented. The wave function and matrix elements of
      relativistic operators are obtained by using recursion relations. Apart from the
      relativistic contribution, we obtain the nuclear polarizability correction for
      11Li. The resulting difference of the squared charge radii 11Li-7Li based on the
      measurements of Sanchez et al. [Phys. Rev. Lett. 96, 033002
      (2006)10.1103/PhysRevLett.96.033002] is deltar(ch)(2)=0.157(81) fm(2), which
      significantly differs from the previous evaluation.

PMID- 17026028
TI  - Isospin symmetry of odd-odd mirror nuclei: identification of excited states in
      N=Z-2 48Mn.
AB  - Excited states have been observed in the N=Z-2 odd-odd nucleus 48Mn for the first
      time. Through comparison with the structure of 48V, a first high-spin study of an
      odd-odd mirror pair has been achieved. Differences between the T=1 analogue
      states in this pair have been interpreted in terms of Coulomb effects, with the
      aid of shell-model calculations in the full pf valence space. Unlike other mirror
      pairs, the energy differences have been interpreted almost entirely as due to a
      monopole effect associated with smooth changes in radius (or deformation) as a
      function of angular momentum. In addition, the large energy shift between
      analogue negative-parity states is interpreted in terms of the electromagnetic
      spin-orbit interaction in nuclei.

PMID- 17026030
TI  - Collision-induced dissociation of hydrated adenosine monophosphate nucleotide
      ions: protection of the ion in water nanoclusters.
AB  - Fragmentation of singly charged anions of adenosine 5'-monophosphate (AMP-)
      induced by collisions with neutral atoms (Ne, Na) has been studied at a collision
      energy of 50 keV. The experiments were performed with isolated AMP- as well as
      with AMP- anions nanosolvated in a cluster with a given number m of water
      molecules. In the first case, the dominant fragmentation channels concern the
      loss of adenine, PO3- and H2PO4-. In the latter, loss of water molecules becomes
      the dominating process, and the AMP- ion is fully protected when m is larger than
      approximately 13. The observed fragment distributions are well described with the
      model of an evaporative ensemble.

PMID- 17026031
TI  - Coarsening and pearling instabilities in silver nanofractal aggregates.
AB  - We investigate the morphological changes of 3D supported fractal aggregates
      generated through the deposition of silver clusters on graphite. The fractal
      relaxation, activated after their formation by perturbing them either by thermal
      annealing or by using a surfactant, as oxide molecules, carried by silver
      clusters in a subsequent deposition, shows evidence of two distinct fragmentation
      patterns. The post coarsening, driven by thermal heating, gives a broad
      asymmetrical distribution of fragments in agreement with a random process,
      whereas the entire silver fractal pearling fragmentation is driven by chemical
      adjunction of the surfactant.

PMID- 17026032
TI  - High-sensitivity optical monitoring of a micromechanical resonator with a quantum
      limited optomechanical sensor.
AB  - We experimentally demonstrate the high-sensitivity optical monitoring of a
      micromechanical resonator and its cooling by active control. Coating a low-loss
      mirror upon the resonator, we have built an optomechanical sensor based on a very
      high-finesse cavity (30 000). We have measured the thermal noise of the resonator
      with a quantum-limited sensitivity at the 10(-19) m/sqrt[Hz] level, and cooled
      the resonator down to 5 K by a cold-damping technique. Applications of our setup
      range from quantum optics experiments to the experimental demonstration of the
      quantum ground state of a macroscopic mechanical resonator.

PMID- 17026033
TI  - Reduction of guided acoustic wave Brillouin scattering in photonic crystal
      fibers.
AB  - Guided acoustic wave Brillouin scattering (GAWBS) generates phase and
      polarization noise of light propagating in glass fibers. This excess noise
      affects the performance of various experiments operating at the quantum noise
      limit. We experimentally demonstrate the reduction of GAWBS noise in a photonic
      crystal fiber in a broad frequency range by tailoring the acoustic modes using
      the photonic also as a phononic crystal. We compare the noise spectrum to the one
      of a standard fiber and observe a tenfold noise reduction in the frequency range
      up to 200 MHz. Based on our measurement results as well as on numerical
      simulations, we establish a model for the reduction of GAWBS noise in photonic
      crystal fibers.

PMID- 17026034
TI  - Optical momentum transfer to absorbing mie particles.
AB  - The momentum transfer to absorbing particles is derived from the Lorentz force
      density without prior assumption of the momentum of light in media. We develop a
      view of momentum conservation rooted in the stress tensor formalism that is based
      on the separation of momentum contributions to bound and free currents and
      charges consistent with the Lorentz force density. This is in contrast with the
      usual separation of material and field contributions. The theory is applied to
      predict a decrease in optical momentum transfer to Mie particles due to
      absorption, which contrasts the common intuition based on the scattering and
      absorption by Rayleigh particles.

PMID- 17026035
TI  - Dissipative viscoplastic deformation in dynamic fracture: tip blunting and
      velocity selection.
AB  - Dynamic fracture in a wide class of materials reveals a "fracture energy" Gamma
      much larger than the expected nominal surface energy due to the formation of two
      fresh surfaces. Moreover, the fracture energy depends on the crack velocity,
      Gamma=Gamma(upsilon). We show that a simple dynamical theory of viscoplasticity
      coupled to asymptotic pure linear elasticity provides a possible explanation to
      the above phenomena. The theory predicts tip blunting characterized by a
      dynamically determined crack tip radius of curvature. In addition, we demonstrate
      velocity selection for cracks in fixed-grip strip geometry accompanied by the
      identification of Gamma and its velocity dependence.

PMID- 17026027
TI  - Strange baryon resonance production in sqrt s NN=200 GeV p+p and Au+Au
      collisions.
AB  - We report the measurements of Sigma(1385) and Lambda(1520) production in p+p and
      Au+Au collisions at sqrt[s{NN}]=200 GeV from the STAR Collaboration. The yields
      and the p(T) spectra are presented and discussed in terms of chemical and thermal
      freeze-out conditions and compared to model predictions. Thermal and microscopic
      models do not adequately describe the yields of all the resonances produced in
      central Au+Au collisions. Our results indicate that there may be a time span
      between chemical and thermal freeze-out during which elastic hadronic
      interactions occur.

PMID- 17026036
TI  - Multiscale modeling of liquids with molecular specificity.
AB  - The separation between molecular and mesoscopic length and time scales poses a
      severe limit to molecular simulations of mesoscale phenomena. We describe a
      hybrid multiscale computational technique which addresses this problem by keeping
      the full molecular nature of the system where it is of interest and coarse
      graining it elsewhere. This is made possible by coupling molecular dynamics with
      a mesoscopic description of realistic liquids based on Landau's fluctuating
      hydrodynamics. We show that our scheme correctly couples hydrodynamics and that
      fluctuations, at both the molecular and continuum levels, are thermodynamically
      consistent. Hybrid simulations of sound waves in bulk water and reflected by a
      lipid monolayer are presented as illustrations of the scheme.

PMID- 17026037
TI  - Dynamics of a deformable body in a fast flowing soap film.
AB  - We study the behavior of an elastic loop embedded in a flowing soap film. This
      deformable loop is wetted into the film and is held fixed at a single point
      against the oncoming flow. We interpret this system as a two-dimensional flexible
      body interacting in a two-dimensional flow. This coupled fluid-structure system
      shows bistability, with both stationary and oscillatory states. In its stationary
      state, the loop remains essentially motionless and its wake is a von Karman
      vortex street. In its oscillatory state, the loop sheds two vortex dipoles, or
      more complicated vortical structures, within each oscillation period. We find
      that the oscillation frequency of the loop is linearly proportional to the flow
      velocity, and that the measured Strouhal numbers can be separated based on wake
      structure.

PMID- 17026038
TI  - Experimental observation of direct particle acceleration by stimulated emission
      of radiation.
AB  - We report the first experimental evidence for direct particle acceleration by
      stimulated emission of radiation. In the framework of this proof-of-principle
      experiment, a 45 MeV electron macrobunch was modulated by a high-power CO2 laser
      and then injected into an excited CO2 gas mixture. The emerging microbunches
      experienced a 0.15% relative change in the kinetic energy, in a less than 40 cm
      long interaction region. According to our experimental results, a fraction of
      these electrons have gained more than 200 keV each, implying that such an
      electron has undergone an order of magnitude of 2 x 10(6) collisions of the
      second kind.

PMID- 17026039
TI  - Radial structure of Alfven eigenmodes in the DIII-D tokamak through electron
      cyclotron-emission measurements.
AB  - The spatial structure of toroidal Alfven eigenmodes and reversed shear Alfven
      eigenmodes in DIII-D is obtained from electron-cyclotron-emission measurements.
      Peak measured temperature perturbations are of similar magnitude for both
      toroidal Alfven eigenmodes and reversed shear Alfven eigenmodes and found to be
      deltaT(e)/T(e) approximately equal to 0.5%. Simultaneous measurements of density
      fluctuations using beam-emission spectroscopy indicate deltan(e)/n(e)
      approximately equal to 0.25%. Predictions of the measured temperature and density
      perturbation profiles as well as deltaT(e)/deltan(e) from the ideal
      magnetohydrodynamic code NOVA are in close agreement with experiment.

PMID- 17026040
TI  - Coupling between global geometry and the local hall effect leading to
      reconnection-layer symmetry breaking.
AB  - The coupling between the global reconnection geometry and the local microphysics,
      caused by the Hall effect, is studied during counterhelicity plasma merging in
      the magnetic reconnection experiment. The structure of the reconnection layer is
      significantly modified by reversing the sign of the toroidal fields, which
      affects the manifestation of the Hall effect in the collisionless regime. The
      local two-fluids physics changes the global boundary conditions, and this
      combination effect consequently provides different reconnection rates, magnetic
      field structure, and plasma flow patterns for two different counterhelicity
      merging cases in the collisionless regime.

PMID- 17026041
TI  - Measuring E and B fields in laser-produced plasmas with monoenergetic proton
      radiography.
AB  - Electromagnetic (E/B) fields generated by the interaction with plasmas of long
      pulse, low-intensity laser beams relevant to inertial confinement fusion have
      been measured for the first time using novel monoenergetic proton radiography
      methods. High-resolution, time-gated radiography images of a plastic foil driven
      by a 10(14) W/cm(2) laser implied B fields of approximately 0.5 MG and E fields
      of approximately 1.5 x 10(8) V/m. Simulations of these experiments with
      LASNEX+LSP have been performed and are in overall (though not exact) agreement
      with the data both for field strengths and for spatial distributions; this is the
      first direct experimental test of the laser-generated B-field package in LASNEX.
      The experiments also demonstrated that laser phase plates substantially reduce
      medium-scale chaotic field structure.

PMID- 17026042
TI  - Effect of densification on the density of vibrational states of glasses.
AB  - We studied the effect of densification on the vibrational dynamics of a
      Na(2)FeSi(3)O(8) glass. The density of vibrational states (DOS) has been measured
      using nuclear inelastic scattering. The corresponding changes in the microscopic,
      intermediate-range, and macroscopic properties have also been investigated. The
      results reveal that, in the absence of local structure transformations, the Debye
      level and the glass-specific excess of vibrational states above it have the same
      dependence on density, and the evolution of the DOS is fully described by the
      transformation of the elastic medium.

PMID- 17026043
TI  - (29)Si hyperfine structure of the E(')(alpha) center in amorphous silicon
      dioxide.
AB  - We report a study by electron paramagnetic resonance on the E'(alpha) point
      defect in amorphous silicon dioxide (a-SiO(2)). Our experiments were performed on
      gamma-ray irradiated oxygen-deficient materials and pointed out that the (29)Si
      hyperfine structure of the E'(alpha) consists of a pair of lines split by
      approximately 49 mT. On the basis of the experimental results, a microscopic
      model is proposed for the E'(alpha) center, consisting of a hole trapped in an
      oxygen vacancy with the unpaired electron sp(3) orbital pointing away from the
      vacancy in a back-projected configuration and interacting with an extra oxygen
      atom of the a-SiO(2) matrix.

PMID- 17026044
TI  - Three-dimensional resonant coherent excitation of nonchanneling ions in a
      crystal.
AB  - We have observed resonant coherent excitation (RCE) of H-like Ar(17+) ions
      traveling through a 1 microm-thick Si crystal at an energy of 391 MeV/u in the
      nonchanneling condition. A three-dimensional periodic array of atomic planes
      induces RCE of the nonchanneling ions. The high energy heavy ions together with
      the thin crystal allow us to observe this new RCE through the measurements of the
      charge-state distribution of the emerging ions. The observed resonances are much
      narrower than those of planar-channeling ions due to the absence of the large
      Stark shift caused by the planar potential.

PMID- 17026045
TI  - Scaling exponents for fracture surfaces in homogeneous glass and glassy ceramics.
AB  - We investigate the scaling properties of postmortem fracture surfaces in silica
      glass and glassy ceramics. In both cases, the 2D height-height correlation
      function is found to obey Family-Viseck scaling properties, but with two sets of
      critical exponents, in particular, a roughness exponent zeta approximately 0.75
      in homogeneous glass and zeta approximately 0.4 in glassy ceramics. The ranges of
      length scales over which these two scalings are observed are shown to be below
      and above the size of the process zone, respectively. A model derived from linear
      elastic fracture mechanics in the quasistatic approximation succeeds to reproduce
      the scaling exponents observed in glassy ceramics. The critical exponents
      observed in homogeneous glass are conjectured to reflect the damage screening
      occurring for length scales below the size of the process zone.

PMID- 17026046
TI  - Correlation of primary and secondary relaxations in a supercooled liquid.
AB  - The widespread assumption that primary and secondary relaxations in glass-forming
      materials are independent processes is scrutinized using spin-lattice relaxation
      weighted stimulated-echo spectroscopy. This nuclear magnetic resonance (NMR)
      technique is simultaneously sensitive to the dynamics on well-separated time
      scales. For the deeply supercooled liquid sorbitol, which exhibits a strong
      secondary relaxation, the primary relaxation (that is observable using NMR) can
      be modified by suppressing the contributions of those subensembles which are
      characterized by relatively slow secondary relaxations. This is clear evidence
      for a correlation between primary and secondary relaxation times. In the
      disordered crystal orthocarborane high-frequency processes are absent and
      consequently no such modifications could be achieved.

PMID- 17026047
TI  - Vacancy-assisted diffusion in silicon: a three-temperature-regime model.
AB  - In this Letter we report kinetic lattice Monte Carlo simulations of vacancy
      assisted diffusion in silicon. We show that the observed temperature dependence
      for vacancy migration energy is explained by the existence of three diffusion
      regimes for divacancies. This characteristic has been rationalized with an
      analytical model. In the intermediate temperature regime the divacancy
      dissociation plays a key role and an effective migration energy E{v}{m}
      approximately 2 eV is predicted, computed from either full ab initio values or
      mixed with experimental ones. The exact position of this temperature regime
      strongly depends on vacancy concentration. Previous contradictory experimental
      results are revisited using this viewpoint.

PMID- 17026048
TI  - Single-atom contact mechanics: from atomic scale energy barrier to mechanical
      relaxation hysteresis.
AB  - The potential energy landscape of surfaces governs the dynamics of adsorbed
      molecules, as well as atomic scale friction processes. We measure the potential
      energy landscape of a single-atom tip interacting with a vicinal nonconducting
      NaCl(100) surface in real space using noncontact atomic force microscopy. We find
      that the shape of the potential energy profile is of sinusoidal form with a
      barrier height of 48 meV. Furthermore, we observe a discontinuity in the force
      curves at specific lattice sites, indicating the onset of reversible yet
      hysteretic mechanical relaxations.

PMID- 17026049
TI  - Electrowetting with electrolytes.
AB  - A theory of electrowetting is developed for systems containing an interface
      between two immiscible electrolytic solutions. Laws for the dependence of contact
      angle on electrode potential are presented. Ionic impermeability of the liquid
      liquid interface and nonlinear double-layer responses rationalize observed
      phenomena such as contact-angle saturation and droplet contraction or detachment.
      The theoretical results can be applied to design new, precisely controllable
      microfluidic devices.

PMID- 17026050
TI  - Simple model of skin formation caused by solvent evaporation in polymer
      solutions.
AB  - A simple model is proposed for the skin formation in the evaporation process of a
      polymer solution at a free surface. In this model the skin is regarded as a gel
      phase formed near the free surface, and the dynamics is described by a diffusion
      equation for the polymer concentration with moving boundaries. The equation is
      solved both analytically and numerically. It is shown that the skin phase appears
      when the evaporation rate is high or when the initial polymer concentration is
      high. An analytical expression is given for the criterion for the skin phase to
      be formed.

PMID- 17026051
TI  - Wetting transitions in polydisperse fluids.
AB  - The properties of the coexisting bulk gas and liquid phases of a polydisperse
      fluid depend not only on the prevailing temperature but also on the overall
      parent density. As a result, a polydisperse fluid near a wall will exhibit
      density-driven wetting transitions inside the coexistence region. We propose a
      likely topology for the wetting phase diagram, which we test using Monte Carlo
      simulations of a model polydisperse fluid at an attractive wall, tracing the
      wetting line inside the cloud curve and identifying the relationship to
      prewetting.

PMID- 17026052
TI  - Sharp corners in the cross section of ultrathin Si nanowires.
AB  - We have determined stable geometries for pristine Si nanowires grown along their
      100 axis through systematic density functional studies. Strikingly, Si nanowires
      with diameters smaller than 1.7 nm prefer a shape that has a square cross
      section. This stems from dimerization between corner atoms and also from benign
      reconstruction patterns that maximally saturate Si dangling bonds.

PMID- 17026053
TI  - Predictions and observations of multiple slip modes in atomic-scale friction.
AB  - Using the quasistatic Tomlinson model as a simple representation of an atomic
      force microscope, conditions for transitions in atomic-scale friction behavior
      from smooth sliding to single slips and then multiple slip regimes are derived
      based on energy minimization. The calculations predict and give a general
      explanation for transitions between different stick-slip regimes in the limit of
      low damping. The predictions are consistent with experimental observations of
      these transitions.

PMID- 17026054
TI  - Role of Au(+) in supporting and activating Au(7) on TiO(2)(110).
AB  - The adhesion properties and catalytic activity of rutile TiO(2)(110)-supported
      Au(7) nanoclusters in different oxidation states are investigated by means of
      density functional theory. The calculations cover both surface science conditions
      of reduced TiO(2) and real catalyst conditions of oxidized (alkaline) TiO(2)
      supports. Large adhesion energies of Au(7) are found only when modeling real
      catalysts where the cluster becomes cationic with Au(+) ions in Au-O or Au-OH
      bonds. The full catalytic cycle for oxidation of CO by O(2) over Au(7) on
      alkaline TiO(2)(110) is calculated and found to involve only small activation
      barriers. In the presence of the CO reductant, the Au(+) sites are capable of
      cycling between bonding of atomic and molecular oxygen. We confirm our findings
      by comparison of calculated and experimental infrared stretch frequency data for
      adsorbed CO.

PMID- 17026055
TI  - Breakup of the Fermi surface near the mott transition in low-dimensional systems.
AB  - We investigate the Mott transition in weakly coupled one-dimensional (1D)
      fermionic chains. Using a generalization of dynamical mean field theory, we show
      that the Mott gap is suppressed at some critical hopping t{ perpendicular}{c2}.
      The transition from the 1D insulator to a 2D metal proceeds through an
      intermediate phase where the Fermi surface is broken into electron and hole
      pockets. The quasiparticle spectral weight is strongly anisotropic along the
      Fermi surface, both in the intermediate and metallic phases. We argue that such
      pockets would look like "arcs" in photoemission experiments.

PMID- 17026056
TI  - SU(2) gauge theory of the Hubbard model: emergence of an anomalous metallic phase
      near the Mott critical point.
AB  - We propose one possible mechanism for an anomalous metallic phase appearing
      frequently in two spatial dimensions, that is, local pairing fluctuations.
      Introducing a pair-rotor representation to decompose bare electrons into
      collective pairing excitations and renormalized electrons, we derive an SU(2)
      gauge theory of the Hubbard model as an extended version of its U(1) gauge
      theory. Since our effective SU(2) gauge theory admits two kinds of collective
      bosons corresponding to pair excitations and density fluctuations, respectively,
      an intermediate phase appears naturally between the spin liquid Mott insulator
      and Fermi liquid metal of the U(1) gauge theory, characterized by softening of
      density-fluctuation modes as the Fermi liquid, but gapping of pair-excitation
      modes. We show that this intermediate phase is identified with an anomalous
      metallic phase because there are no electronlike quasiparticles although it is
      metallic.

PMID- 17026057
TI  - Direct evidence for conduction pathways in a solid electrolyte.
AB  - The emission of silver ions from the apex of an amorphous electrolyte tip has
      been investigated by field ion microscopy. The ion emission patterns show
      discrete nanometer-sized spots. We present evidence that they represent the
      termination of bulk ion conduction pathways at the solid-vacuum interface. The
      analysis of the signals from individual emission sites suggests the existence of
      a network of such pathways in the solid. Auto- and cross-correlation measurements
      of the currents from individual sites provide quantitative information on the
      microscopic dynamics of charge transport in solid electrolytes as well as on the
      lateral extent of the pathway network.

PMID- 17026059
TI  - Intrinsic domain-wall resistance in ferromagnetic semiconductors.
AB  - Transport through zinc blende magnetic semiconductors with magnetic domain walls
      is studied theoretically. We show that these magnetic domain walls have an
      intrinsic resistance due to the effective hole spin-orbit interaction. The
      intrinsic resistance is independent of the domain-wall shape and width and
      survives the adiabatic limit. For typical parameters, the intrinsic domain-wall
      resistance is comparable to the Sharvin resistance and should be experimentally
      measurable.

PMID- 17026058
TI  - Optical measurement and control of spin diffusion in n-doped GaAs quantum wells.
AB  - Transient spin gratings are used to study spin diffusion in lightly n-doped GaAs
      quantum wells at low temperatures. The spin grating is shown to form in the
      excess electrons from doping, providing spin relaxation and transport properties
      of the carriers most relevant to spintronic applications. We demonstrate that
      spin diffusion of the these carriers is accelerated by increasing the density or
      energy of the optically excited carriers. These results can be used to better
      understand and even control spin transport in experiments that optically excite
      spin-polarized carriers.

PMID- 17026060
TI  - Spin correlations and finite-size effects in the one-dimensional kondo box.
AB  - We analyze the Kondo effect of a magnetic impurity attached to an ultrasmall
      metallic wire using the density matrix renormalization group. The spatial spin
      correlation function and the impurity spectral density are computed for system
      sizes of up to L=511 sites, covering the crossover from L<l{K} to L>l{K}, with
      l{K} the spin screening length. We establish a proportionality between the weight
      of the Kondo resonance and l{K} as a function of L. This suggests a spectroscopic
      way of detecting the Kondo cloud.

PMID- 17026061
TI  - Effect of strain on the carrier mobility in heavily doped p-type Si.
AB  - We present an experiment that gives insight into the origin of the dependence of
      the hole mobility (mu) on the dopant species in heavily doped p-type Si under low
      electrical field. The Hall carrier concentration and mobility were measured in Si
      coimplanted with B and Ga in the 0.1-2 x 10{20} cm{-3} concentration range. The
      strain induced by substitutional dopants, detected by high resolution x-ray
      diffraction, was varied by changing the relative B and Ga concentration. The
      effect of strain on mobility was disentangled and a linear relationship between
      1/mu and the perpendicular strain was found.

PMID- 17026062
TI  - Magnetic fullerenes inside single-wall carbon nanotubes.
AB  - C(59)N magnetic fullerenes were formed inside single-wall carbon nanotubes by
      vacuum annealing functionalized C(59)N molecules encapsulated inside the tubes. A
      hindered, anisotropic rotation of C(59)N was deduced from the temperature
      dependence of the electron spin resonance spectra near room temperature.
      Shortening of the spin-lattice relaxation time T(1) of C(59)N indicates a
      reversible charge transfer toward the host nanotubes above approximately 350 K.
      Bound C(59)N-C(60) heterodimers are formed at lower temperatures when C(60) is
      coencapsulated with the functionalized C(59)N. In the 10-300 K range, T(1) of the
      heterodimer shows a relaxation dominated by the conduction electrons on the
      nanotubes.

PMID- 17026063
TI  - Magnetic-field enhancement of superconductivity in ultranarrow wires.
AB  - We study the effect of an applied magnetic field on sub-10-nm wide MoGe and Nb
      superconducting wires. We find that magnetic fields can enhance the critical
      supercurrent at low temperatures, and do so more strongly for narrower wires. We
      conjecture that magnetic moments are present, but their pair-breaking effect,
      active at lower magnetic fields, is suppressed by higher fields. The
      corresponding microscopic theory, which we have developed, quantitatively
      explains all experimental observations, and suggests that magnetic moments have
      formed on the wire surfaces.

PMID- 17026064
TI  - Symmetric and asymmetric vortex-antivortex molecules in a fourfold
      superconducting geometry.
AB  - In submicron superconducting squares in a homogeneous magnetic field, Ginzburg
      Landau theory may admit solutions of the vortex-antivortex type, conforming to
      the symmetry of the sample [L. F. Chibotaru, Nature (London) 408, 833
      (2000)10.1038/35048521]. Here we show that these fascinating, but never
      experimentally observed states, can be enforced by artificial fourfold pinning,
      with their diagnostic features enhanced by orders of magnitude. The second-order
      nucleation of vortex-antivortex molecules can be driven by either temperature or
      an applied magnetic field, with stable asymmetric vortex-antivortex equilibria
      found on its path.

PMID- 17026065
TI  - Phase textures induced by dc-current pair breaking in weakly coupled multilayer
      structures and two-gap superconductors.
AB  - We predict the current-induced formation of equilibrium phase textures for a
      multicomponent superconducting order parameter. Using the two-component Ginzburg
      Landau and Usadel equations, we show that, for weakly coupled comoving
      superconducting condensates, the dc current I first causes the breakdown of the
      phase-locked state at I>I{c1} followed by the formation of intrinsic phase
      textures well below the depairing current I{d}. These phase textures can manifest
      themselves in multilayer structures, atomic Bose condensate mixtures in optical
      lattices, and two-gap superconductors, particularly MgB(2), where they can result
      in oscillating and resistive switching effects.

PMID- 17026066
TI  - Critical behavior of Griffiths ferromagnets.
AB  - From a heuristic calculation of the leading order essential singularity in the
      distribution of Yang-Lee zeroes, we obtain new scaling relations near the
      ferromagnetic-Griffiths transition, including the prediction of a discontinuity
      on the analogue of the critical isotherm. We show that experimental data for the
      magnetization and heat capacity of La(0.7)Ca(0.3)MnO(3) are consistent with these
      predictions, thus supporting its identification as a Griffiths ferromagnet.

PMID- 17026067
TI  - Dynamics of a pinned magnetic vortex.
AB  - We observe the dynamics of a single magnetic vortex pinned by a defect in a
      ferromagnetic film. At low excitation amplitudes, the vortex core gyrates about
      its equilibrium position with a frequency that is characteristic of a single
      pinning site. At high amplitudes, the frequency of gyration is determined by the
      magnetostatic energy of the entire vortex, which is confined in a micron-scale
      disk. We observe a sharp transition between these two amplitude regimes that is
      due to depinning of the vortex core from a local defect. The distribution of
      pinning sites is determined by mapping fluctuations in the frequency as the
      vortex core is displaced by a static in-plane magnetic field.

PMID- 17026068
TI  - Determination of the antiferroquadrupolar order parameters in UPd(3).
AB  - By combining accurate heat capacity and x-ray resonant scattering results we have
      resolved the long standing question regarding the nature of the quadrupolar
      ordered phases in UPd(3). The order parameter of the highest temperature
      quadrupolar phase has been uniquely determined to be antiphase Q{zx} in contrast
      to the previous conjecture of Q{x{2}-y{2}}. The azimuthal dependence of the x-ray
      scattering intensity from the quadrupolar superlattice reflections indicates that
      the lower temperature phases are described by a superposition of order
      parameters. The heat capacity features associated with each of the phase
      transitions characterize their order, which imposes restrictions on the matrix
      elements of the quadrupolar operators.

PMID- 17026069
TI  - Quantum spin glass and the dipolar interaction.
AB  - Anisotropic dipolar systems are considered. Such systems in an external magnetic
      field are expected to be a good experimental realization of the transverse field
      Ising model. With random interactions, this model yields a spin glass to
      paramagnet phase transition as a function of the transverse field. We show that
      the off-diagonal dipolar interaction, although effectively reduced, induces a
      finite correlation length and thus destroys the spin-glass order at any finite
      transverse field. We thus explain the behavior of the nonlinear susceptibility in
      the experiments on LiHo(x)Y(1-x)F(4), and argue that a crossover to the
      paramagnetic phase, and not quantum criticality, is observed.

PMID- 17026070
TI  - Opposite spin asymmetry of elastic and inelastic scattering of nonequilibrium
      holes injected into a ferromagnet.
AB  - The spin asymmetry of elastic and inelastic scattering of nonequilibrium holes
      injected into Co thin films is examined using a p-type magnetic tunnel
      transistor. Spin-dependent transmission yields a positive or negative
      magnetocurrent depending on Co thickness and hole energy. Up to a critical
      thickness of about 3 nm, (quasi)elastic scattering dominates with a short
      attenuation length (<1 nm) and preferential attenuation of holes in the majority
      spin bands, consistent with spin-wave emission. At a larger Co thickness,
      inelastic scattering dominates with a larger attenuation length ( approximately 4
      nm) and opposite spin asymmetry.

PMID- 17026071
TI  - Electron spin resonance of proton-irradiated graphite.
AB  - In the case of colossal magnetoresistance in the perovskite manganites, "double
      exchange" mediated by the itinerant spins is believed to play a key role in the
      ferromagnetism. In contrast, the conventional "Heisenberg" interaction, i.e.,
      direct (unmediated) interaction between the localized spins produced by the
      proton irradiation, is identified as the origin of proton irradiation-induced
      ferromagnetism in graphite.

PMID- 17026072
TI  - Easily coupled whispering gallery plasmons in dielectric nanospheres embedded in
      gold films.
AB  - A new self-aligned robust method for coupling to whispering gallery modes (WGMs)
      of submicron microspheres utilizes their periodic arrangement without relying on
      nanopositioned external coupling devices. The microspheres are embedded in a
      nanostructured gold surface supporting delocalized plasmonic crystal modes that
      mediate the coupling, and can be tuned by the geometry. Detailed measurements of
      the angle- and orientation-dependent reflectivity reveal localized plasmonic WGMs
      whose energies scale with sphere diameter and agree closely with Mie
      calculations. Coupling between these plasmonic WGMs leads to mode splitting and
      the formation of plasmonic minibands of a controllable bandwidth.

PMID- 17026073
TI  - Ab initio calculation of optical spectra of liquids: many-body effects in the
      electronic excitations of water.
AB  - We present ab initio calculations of the excited state properties of liquid water
      in the framework of many-body Green's function formalism. Snapshots taken from
      molecular dynamics simulations are used as input geometries to calculate
      electronic and optical spectra, and the results are averaged over the different
      configurations. The optical absorption spectra with the inclusion of excitonic
      effects are calculated by solving the Bethe-Salpeter equation. The insensitivity
      of screening effects to a particular configuration make these calculations
      feasible. The resulting spectra, which are strongly modified by many-body
      effects, are in good agreement with experiments.

PMID- 17026074
TI  - Origin of the relaxor state in Pb(B{x}B{1-x}{'})O(3) perovskites.
AB  - Molecular dynamics simulations of first-principles-based effective Hamiltonians
      for Pb(Sc{1/2}Nb{1/2})O(3) under hydrostatic pressure and for
      Pb(Mg{1/3}Nb{2/3})O(3) at ambient pressure show clear evidence of a relaxor state
      in both systems. The Burns temperature is identified as the temperature below
      which dynamic nanoscale polar clusters form, pinned to regions of quenched
      chemical short-range order. The effect of pressure in Pb(Sc{1/2}Nb{1/2})O(3)
      demonstrates that the stability of the relaxor state depends on a delicate
      balance between the energetics that stabilize normal ferroelectricity and the
      average strength of random local fields which promote the relaxor state.

PMID- 17026075
TI  - Water percolation governs polymorphic transitions and conductivity of DNA.
AB  - We report on the first computer simulation studies of the percolation transition
      of water at the surface of the DNA double helix. With increased hydration, the
      ensemble of small clusters merges into a spanning water network via a quasi-two
      dimensional percolation transition. This transition occurs strikingly close to
      the hydration level where the B form of DNA becomes stable in experiment.
      Formation of spanning water networks results in sigmoidlike acceleration of long
      range ion transport in good agreement with experiment.

PMID- 17026076
TI  - Critical role of gravity in filters.
AB  - The efficiency of filters depends crucially on the mass of the particles one
      wants to capture. Using analytical and numerical calculations we reveal a very
      rich scenario of scaling laws relating this efficiency to particle size and
      density and the velocity and viscosity of the carrying fluid. These are combined
      in the dimensionless, so-called Stokes number St. In the case of horizontal flow
      or neutrally buoyant particles, we find a critical number St{c} below which no
      particles are trapped; i.e., the filter does not work. Above St{c} the capture
      efficiency increases like the square root of (St-St{c}). Under the action of
      gravity, the threshold abruptly vanishes and capture occurs at any Stokes number
      increasing linearly in St. We discovered further scaling laws in the penetration
      profile and as function of the porosity of the filter.

PMID- 17026077
TI  - Shear-flow-induced unfolding of polymeric globules.
AB  - The behavior of a single collapsed polymer under shear flow is examined using
      hydrodynamic simulations and scaling arguments. Below a threshold shear rate
      gamma[.]{*}, the chain remains collapsed and only deforms slightly, while above
      gamma[.]{*} the globule exhibits unfolding/refolding cycles. Hydrodynamics are
      crucial: In the free draining case, gamma[.]{*} scales with the globule radius R
      as gamma[.]{*} approximately R{-1}, while in the presence of hydrodynamic
      interactions gamma[.]{*} approximately R. Experiments on the globular von
      Willebrand protein confirm the presence of an unfolding transition at a well
      defined critical shear rate.

PMID- 17026078
TI  - Tissue self-affinity and polarized light scattering in the born approximation: a
      new model for precancer detection.
AB  - Light scattered from biological tissues can exhibit an inverse power law spectral
      component. We develop a model based on the Born approximation and von Karman
      (self-affine) spatial correlation of submicron tissue refractive index to account
      for this. The model is applied to light scattering spectra obtained from excised
      esophagi of normal and carcinogen-treated rats. Power law exponents used to fit
      dysplastic tissue site spectra are significantly smaller than those from normal
      sites, indicating that changes in tissue self-affinity can serve as a potential
      biomarker for precancer.

PMID- 17026079
TI  - Efficiency of initiating cell adhesion in hydrodynamic flow.
AB  - We theoretically investigate the efficiency of initial binding between a receptor
      coated sphere and a ligand-coated wall in linear shear flow. The mean first
      passage time for binding decreases monotonically with increasing shear rate.
      Above a saturation threshold of the order of a few 100 receptor patches, the
      binding efficiency is enhanced only weakly by increasing their number and size,
      but strongly by increasing their height. This explains why white blood cells in
      the blood flow adhere through receptor patches localized to the tips of
      microvilli, and why malaria-infected red blood cells form elevated receptor
      patches (knobs).

PMID- 17026080
TI  - Lieb-Robinson bounds and the generation of correlations and topological quantum
      order.
AB  - The Lieb-Robinson bound states that local Hamiltonian evolution in
      nonrelativistic quantum mechanical theories gives rise to the notion of an
      effective light cone with exponentially decaying tails. We discuss several
      consequences of this result in the context of quantum information theory. First,
      we show that the information that leaks out to spacelike separated regions is
      negligible and that there is a finite speed at which correlations and
      entanglement can be distributed. Second, we discuss how these ideas can be used
      to prove lower bounds on the time it takes to convert states without topological
      quantum order to states with that property. Finally, we show that the rate at
      which entropy can be created in a block of spins scales like the boundary of that
      block.

PMID- 17026081
TI  - Spectroscopy of ultracold atoms by periodic lattice modulations.
AB  - We present a nonperturbative analysis of a new experimental technique for probing
      ultracold bosons in an optical lattice by periodic lattice depth modulations.
      This is done using the time-dependent density-matrix renormalization group
      method. We find that sharp energy absorption peaks are not unique to the Mott
      insulating phase at commensurate filling but also exist for superfluids at
      incommensurate filling. For strong interactions, the peak structure provides an
      experimental measure of the interaction strength. Moreover, the peak height of
      the peaks at Planck's omega > or approximately 2U can be employed as a measure of
      the incommensurability of the system.

PMID- 17026082
TI  - E expansion for a Fermi gas at infinite scattering length.
AB  - We show that there exists a systematic expansion around four spatial dimensions
      for Fermi gas in the unitarity regime. We perform the calculations to leading and
      next-to-leading orders in the expansion over E = 4-d, where d is the
      dimensionality of space. We find the ratio of chemical potential and Fermi energy
      to be mu/epsilon(F) =1/2 (E 3/2) + 1/16 (E 5/2) lnE -0.0246E (5/2) + ... and the
      ratio of the gap in the fermion quasiparticle spectrum and the chemical potential
      to be Delta/mu =2E(-1) - 0.691 + ... . The minimum of the fermion dispersion
      curve is located at |p|=(2mepsilon(0))(1/2), where epsilon_(0)/mu=2+O(E).
      Extrapolation to d=3 gives results consistent with Monte Carlo simulations.

PMID- 17026083
TI  - Entanglement entropy of 2D conformal quantum critical points: hearing the shape
      of a quantum drum.
AB  - The entanglement entropy of a pure quantum state of a bipartite system A union or
      logical sumB is defined as the von Neumann entropy of the reduced density matrix
      obtained by tracing over one of the two parts. In one dimension, the entanglement
      of critical ground states diverges logarithmically in the subsystem size, with a
      universal coefficient that for conformally invariant critical points is related
      to the central charge of the conformal field theory. We find that the
      entanglement entropy of a standard class of z=2 conformal quantum critical points
      in two spatial dimensions, in addition to a nonuniversal "area law" contribution
      linear in the size of the AB boundary, generically has a universal
      logarithmically divergent correction, which is completely determined by the
      geometry of the partition and by the central charge of the field theory that
      describes the critical wave function.

PMID- 17026084
TI  - Measuring multipartite concurrence with a single factorizable observable.
AB  - We show that, for any composite system with an arbitrary number of finite
      dimensional subsystems, it is possible to directly measure the multipartite
      concurrence of pure states by detecting only one single factorizable observable,
      provided that two copies of the composite state are available. This result can be
      immediately put into practice in trapped-ion and entangled-photon experiments.

PMID- 17026085
TI  - State tomography of capacitively shunted phase qubits with high fidelity.
AB  - We introduce a new design concept for superconducting phase quantum bits (qubits)
      in which we explicitly separate the capacitive element from the Josephson tunnel
      junction for improved qubit performance. The number of two-level systems that
      couple to the qubit is thereby reduced by an order of magnitude and the
      measurement fidelity improves to 90%. This improved design enables the first
      demonstration of quantum state tomography with superconducting qubits using
      single-shot measurements.

PMID- 17026086
TI  - Asymptotic violation of Bell inequalities and distillability.
AB  - A multipartite quantum state violates a Bell inequality asymptotically if, after
      jointly processing by general local operations an arbitrarily large number of
      copies of it, the result violates the inequality. In the bipartite case we show
      that asymptotic violation of the Clauser-Horne-Shimony-Holt inequality is
      equivalent to distillability. Hence, bound entangled states do not violate it. In
      the multipartite case we consider the complete set of full-correlation Bell
      inequalities with two dichotomic observables per site. We show that asymptotic
      violation of any of these inequalities by a multipartite state implies that pure
      state entanglement can be distilled from it, although the corresponding
      distillation protocol may require that some of the parties join into several
      groups. We also obtain the extreme points of the set of distributions generated
      by measuring N quantum systems with two dichotomic observables per site.

PMID- 17026087
TI  - Limitations of quantum simulation examined by simulating a pairing Hamiltonian
      using nuclear magnetic resonance.
AB  - Quantum simulation uses a well-known quantum system to predict the behavior of
      another quantum system. Certain limitations in this technique arise, however,
      when applied to specific problems, as we demonstrate with a theoretical and
      experimental study of an algorithm proposed by Wu, Byrd, and Lidar [Phys. Rev.
      Lett. 89, 057904 (2002).10.1103/PhysRevLett.89.057904] to find the low-lying
      spectrum of a pairing Hamiltonian. While the number of elementary quantum gates
      required scales polynomially with the size of the system, it increases inversely
      to the desired error bound E. Making such simulations robust to decoherence using
      fault tolerance requires an additional factor of approximately 1/E gates. These
      constraints, along with the effects of control errors, are illustrated using a
      three qubit NMR system.

PMID- 17026088
TI  - Trapped ion quantum computation with transverse phonon modes.
AB  - We propose a scheme to implement quantum gates on any pair of trapped ions
      immersed in a large linear crystal, using interaction mediated by the transverse
      phonon modes. Compared with the conventional approaches based on the longitudinal
      phonon modes, this scheme is much less sensitive to ion heating and thermal
      motion outside of the Lamb-Dicke limit thanks to the stronger confinement in the
      transverse direction. The cost for such a gain is only a moderate increase of the
      laser power to achieve the same gate speed. We also show how to realize arbitrary
      speed quantum gates with transverse phonon modes based on simple shaping of the
      laser pulses.

PMID- 17026089
TI  - Statistical-temperature Monte Carlo and molecular dynamics algorithms.
AB  - A simulation method is presented that achieves a flat energy distribution by
      updating the statistical temperature instead of the density of states in Wang
      Landau sampling. A novel molecular dynamics algorithm (STMD) applicable to
      complex systems and a Monte Carlo algorithm are developed from this point of
      view. Accelerated convergence for large energy bins, essential for large systems,
      is demonstrated in tests on the Ising model, the Lennard-Jones fluid, and bead
      models of proteins. STMD shows a superior ability to find local minima in
      proteins and new global minima are found for the 55 bead AB model in two and
      three dimensions. Calculations of the occupation probabilities of individual
      protein inherent structures provide new insights into folding and misfolding.

PMID- 17026090
TI  - Measurement of stochastic entropy production.
AB  - Using fluorescence spectroscopy we directly measure entropy production of a
      single two-level system realized experimentally as an optically driven defect
      center in diamond. We exploit a recent suggestion to define entropy on the level
      of a single stochastic trajectory [Seifert, Phys. Rev. Lett. 95, 040602
      (2005)10.1103/PhysRevLett.95.040602]. Entropy production can then be split into
      one of the system itself and one of the surrounding medium. We demonstrate that
      the total entropy production obeys various exact relations for finite time
      trajectories.

PMID- 17026091
TI  - Exclusion processes with internal states.
AB  - We introduce driven exclusion processes with internal states that serve as
      generic transport models in various contexts, ranging from molecular or vehicular
      traffic on parallel lanes to spintronics. The ensuing nonequilibrium steady
      states are controllable by boundary as well as bulk rates. A striking
      polarization phenomenon accompanied by domain wall motion and delocalization is
      discovered within a mesoscopic scaling. We quantify this observation within an
      analytic description providing exact phase diagrams. Our results are confirmed by
      stochastic simulations.

PMID- 17026092
TI  - High energy neutrino flashes from far-ultraviolet and x-ray flares in gamma-ray
      bursts.
AB  - The recent observations of bright optical and x-ray flares by the Swift satellite
      suggest these are produced by the late activities of the central engine. We study
      the neutrino emission from far-ultraviolet and x-ray flares under the late
      internal shock model. We show that the efficiency of pion production in the
      highest energy is comparable to or higher than the unity, and the contribution
      from such neutrino flashes to a diffuse very high energy neutrino background can
      be larger than that of prompt bursts if the total baryonic energy input into
      flares is comparable to the radiated energy of prompt bursts. These signals may
      be detected by IceCube and are very important because they have possibilities to
      probe the nature of flares (the baryon loading, the photon field, the magnetic
      field and so on).

PMID- 17026093
TI  - Implications of direct dark matter constraints for minimal supersymmetric
      standard model Higgs boson searches at the Tevatron.
AB  - In regions of large tanbeta and small mAlpha, searches for heavy neutral minimal
      supersymmetric standard model (MSSM) Higgs bosons at the Tevatron are promising.
      At the same time, rates in direct dark matter experiments, such as CDMS, are
      enhanced in the case of large tanbeta and small mAlpha. As a result, there is a
      natural interplay between the heavy, neutral Higgs searches at the Tevatron and
      the region of parameter space explored by CDMS. We show that if the lightest
      neutralino makes up the dark matter of our universe, current limits from CDMS
      strongly constrain the prospects of heavy, neutral MSSM Higgs discovery at the
      Tevatron unless |mu| greater or approximately 400 GeV. The limits of CDMS
      projected for 2007 will increase this constraint to |mu| greater or approximately
      800 GeV. If CDMS does observe neutralinos in the near future, however, it will
      make the discovery of Higgs bosons at the Tevatron far more likely.

PMID- 17026096
TI  - Neutron and proton transverse emission ratio measurements and the density
      dependence of the asymmetry term of the nuclear equation of state.
AB  - Recent measurements of preequilibrium neutron and proton transverse emission from
      (112,124)Sn+(112,124)Sn reactions at 50 MeV/A have been completed at the National
      Superconducting Cyclotron Laboratory. Free nucleon transverse emission ratios are
      compared to those of A=3 mirror nuclei. Comparisons are made to Boltzmann-Uehling
      Uhlenbeck (BUU) transport calculations and conclusions concerning the density
      dependence of the asymmetry term of the nuclear equation of state at subnuclear
      densities are made. Comparison to BUU model predictions indicate a density
      dependence of the asymmetry energy that is closer to a form in which the
      asymmetry energy increases as the square root of the density for the density
      region studied. A coalescent-invariant analysis is introduced as a means of
      reducing suggested difficulties with cluster emission in total nucleon emission.

PMID- 17026097
TI  - Quantum-control spectroscopy with exact state selectivity.
AB  - A method of exact state-selective spectroscopy is introduced, based on quantum
      control through four specific short laser pulses. The exact conditions for the
      two pairs of ultrafast pulses are set by the feedback control for selective
      excitation to one specific resonance state while the other state is destructively
      interfered as the shadow pair, leading to a state-selective spectrum.

PMID- 17026098
TI  - Quantum optics with surface plasmons.
AB  - We describe a technique that enables strong, coherent coupling between individual
      optical emitters and guided plasmon excitations in conducting nanostructures at
      optical frequencies. We show that under realistic conditions optical emission can
      be almost entirely directed into the plasmon modes. As an example, we describe an
      application of this technique involving efficient generation of single photons on
      demand, in which the plasmon is efficiently outcoupled to a dielectric waveguide.

PMID- 17026099
TI  - Experimental investigation of core-valence double photoionization.
AB  - Core-valence double photoionization has been observed in Ne atoms and N2
      molecules using a magnetic-bottle time of flight spectrometer. The multielectron
      coincidence data sets give complete information on the energy correlations
      between all emitted electrons, which supports a detailed description of the core
      valence double photoionization processes including direct spectroscopy of the
      core-valence doubly ionized states, the final states populated by their Auger
      decay and details of the dynamics of core-valence double photoionization for
      selected states.

PMID- 17026100
TI  - Squeezed-state purification with linear optics and feedforward.
AB  - A scheme for optimal and deterministic linear optical purification of mixed
      squeezed Gaussian states is proposed and experimentally demonstrated. The scheme
      requires only linear optical elements and homodyne detectors, and allows the
      balance between purification efficacy and squeezing degradation to be controlled.
      One particular choice of parameters gave a tenfold reduction of the thermal noise
      with a corresponding squeezing degradation of only 11%. We prove optimality of
      the protocol, and show that it can be used to enhance the performance of quantum
      informational protocols such as dense coding and entanglement generation.

PMID- 17026101
TI  - Experimental verification of an optical vortex coronagraph.
AB  - A coronagraph designed for high contrast imaging applications has been
      experimentally tested using coherent laser light and a vortex mask of topological
      charge m=2. Intensity contrast values of 95% were achieved in this first
      verification of the scheme. Improvements for approaching the theoretical value of
      100% are suggested.

PMID- 17026102
TI  - Making tunnel barriers (including metals) transparent.
AB  - The classical "brick wall," which may, according to quantum mechanics, leak via
      tunneling, is here shown to be completely transparent when appropriate impedance
      matching media are placed both in front of and behind the "wall." Optical
      experiments involving beyond-critical-angle-tunnel barriers in the frustrated
      total internal reflection scheme which mimic quantum mechanical systems provide
      convincing proof of this remarkable effect. The same mechanism also allows vastly
      enhanced transmission through unstructured thin metal films without the need for
      surface wave excitation.

PMID- 17026095
TI  - Dense-medium modifications to jet-induced hadron pair distributions in Au+Au
      collisions at sqrt s NN=200 GeV.
AB  - Azimuthal correlations of jet-induced high-p(T) charged hadron pairs are studied
      at midrapidity in Au+Au collisions at sqrt[s(NN)]=200 GeV. The distribution of
      jet-associated partner hadrons (1.0<p(T)<2.5 GeV/c) per trigger hadron
      (2.5<p(T)<4.0 GeV/c) is found to vary with collision centrality, in both shape
      and yield, indicating a significant effect of the nuclear collision medium on the
      jet fragmentation process.

PMID- 17026103
TI  - Recovering the acoustic Green's function from ambient noise cross correlation in
      an inhomogeneous moving medium.
AB  - We study long-range correlation of diffuse acoustic noise fields in an arbitrary
      inhomogeneous, moving fluid. The flow reversal theorem is used to show that the
      cross-correlation function of ambient noise provides an estimate of a combination
      of the Green's functions corresponding to sound propagation in opposite
      directions between the two receivers. Measurements of the noise cross correlation
      allow one to quantify flow-induced acoustic nonreciprocity and evaluate both
      spatially averaged flow velocity and sound speed between the two points.

PMID- 17026104
TI  - Pattern formation in Taylor-Couette flow of dilute polymer solutions: dynamical
      simulations and mechanism.
AB  - We report spatiotemporal pattern formation in Taylor-Couette flow (i.e., flow
      between rotating cylinders) of viscoelastic dilute polymer solutions obtained for
      the first time from first-principles dynamical simulations. Solution structures
      with varying spatial and temporal symmetries, such as rotating standing waves,
      flames, disordered oscillations, and solitary vortex solutions which include
      diwhirls (stationary and axisymmetric) and oscillatory strips (axisymmetric or
      nonaxisymmetric), are observed, depending on the ratio of fluid relaxation time
      to the time period of inner cylinder rotation. The flow-microstructure coupling
      mechanisms underlying the pattern formation process are also discussed.

PMID- 17026105
TI  - Drop deformation in microconfined shear flow.
AB  - The deformation and breakup of a drop in an immiscible equiviscous liquid
      undergoing unbounded shear flow has been extensively investigated in the
      literature, starting from the pioneering work of Taylor. In this Letter, we
      address the case of microconfined shear flow, a problem which is relevant for
      microfluidics and emulsion processing applications. The main effects of
      confinement include complex oscillating transients and drop stabilization against
      breakup. In particular, very elongated drop shapes are observed, which would be
      unstable in the unbounded case and can be explained in terms of wall-induced
      distortion of the shear flow field. We show that wall effects can be exploited to
      obtain nearly monodisperse emulsions in microconfined shear flow.

PMID- 17026106
TI  - Absolute measurement of electron-cloud density in a positively charged particle
      beam.
AB  - Clouds of stray electrons are ubiquitous in particle accelerators and frequently
      limit the performance of storage rings. Earlier measurements of electron energy
      distribution and flux to the walls provided only a relative electron-cloud
      density. We have measured electron accumulation using ions expelled by the beam.
      The ion energy distribution maps the depressed beam potential and gives the
      dynamic cloud density. Clearing electrode current reveals the static background
      cloud density, allowing the first absolute measurement of the time-dependent
      electron-cloud density during the beam pulse.

PMID- 17026107
TI  - Observation and control of transverse energy-transport barrier due to the
      formation of an energetic-electron layer with sheared ExB flow.
AB  - Off-axis electron-cyclotron heating in an axisymmetric barrier mirror produces a
      cylindrical layer with energetic electrons, which flow through the central cell
      and into the end region. The layer, producing a localized bumped ambipolar
      potential Phi(C), forms a strong shear of radial electric fields E(r) and peaked
      vorticity with the direction reversal of E(r)xB sheared flow near the Phi(C)
      peak. Intermittent vortexlike turbulent structures near the layer are suppressed
      in the central cell by this actively produced transverse energy-transport
      barrier; this results in T(e) and T(i) rises surrounded by the layer.

PMID- 17026109
TI  - Stability of highly shifted equilibria in a large-aspect-ratio tokamak.
AB  - High beta poloidal tokamaks can confine plasma pressures an order of magnitude
      higher than their low beta poloidal counterparts. The theoretical stability of
      these high beta poloidal magnetohydrodynamics equilibria was left unresolved for
      many years. Using modern computational tools, such configurations are now found
      stable to Mercier, resistive and high-n (ideal and resistive) ballooning criteria
      as well as fixed and free-boundary modes for a wide range of current density
      profiles in the framework of a low field large-aspect-ratio machine.

PMID- 17026108
TI  - Observation of stable superdense core plasmas in the large helical device.
AB  - In reduced recycling discharges in the Large Helical Device, a super dense core
      plasma develops when a series of pellets are injected. A core region with density
      as high as 4.5 x 10(20) m(-3) and temperature of 0.85 keV is maintained by an
      internal diffusion barrier with very high-density gradient. These results may
      extrapolate to a scenario for fusion ignition at very high density and relatively
      low temperature in helical devices.

PMID- 17026110
TI  - Inhomogeneous elastic response of silica glass.
AB  - Using large scale molecular dynamics simulations we investigate the properties of
      the nonaffine displacement field induced by macroscopic uniaxial deformation of
      amorphous silica, a strong glass according to Angell's classification. We
      demonstrate the existence of a length scale xi characterizing the correlations of
      this field (corresponding to a volume of about 1000 atoms), and compare its
      structure to the one observed in a standard fragile model glass. The "boson-peak"
      anomaly of the density of states can be traced back in both cases to elastic
      inhomogeneities on wavelengths smaller than xi where classical continuum
      elasticity becomes simply unapplicable.

PMID- 17026111
TI  - Imaging ripples on phononic crystals reveals acoustic band structure and Bloch
      harmonics.
AB  - Broadband surface phonon wave packets on a phononic crystal made up of a
      microstructured line pattern are tracked in two dimensions and in real time with
      an ultrafast optical technique. The eigenmode distribution and the 2D acoustic
      band structure are obtained from spatiotemporal Fourier transforms of the data up
      to 1 GHz. We find stop bands at the zone boundaries for both leaky-longitudinal
      and Rayleigh waves, and show how the structure of individual acoustic eigenmodes
      in k space depends on Bloch harmonics and on mode coupling.

PMID- 17026112
TI  - Control of defect concentrations within a semiconductor through adsorption.
AB  - The technologically useful properties of a crystalline solid depend upon the
      concentration of defects it contains. Here we show that defect concentrations as
      deep as 0.5 microm within a semiconductor can be profoundly influenced by gas
      adsorption. Self-diffusion rates within silicon show that nitrogen atoms adsorbed
      at less than 1% of a monolayer lead to defect concentrations that vary
      controllably over several orders of magnitude. The results show that previous
      measurements of diffusion and defect thermodynamics in semiconductors may have
      suffered from neglect of adsorption effects.

PMID- 17026094
TI  - Observation of B0 meson decay to a 1 +/(1260)pi /+.
AB  - We present a measurement of the branching fraction of the decay B(0)-->a1
      (+/)(1260)pi(/+) with a1 (+/)(1260)-->pi(/+)pi(+/)pi(+/). The data sample
      corresponds to 218 x 10(6) BB[over ] pairs produced in e+e- annihilation through
      the Upsilon(4S) resonance. We measure the branching fraction Beta(B(0)-
      >a1(+/)(1260)pi(/+))Beta(a1(+/)(1260)-->pi(/+)pi(+/)pi(+/)) = (16.6+/1.9+/1.5) x
      10(-6), where the first error quoted is statistical and the second is systematic.

PMID- 17026113
TI  - Universal features of terahertz absorption in disordered materials.
AB  - Using an analytical theory, experimental terahertz time-domain spectroscopy data,
      and numerical evidence, we demonstrate that the frequency dependence of the
      absorption coupling coefficient between far-infrared photons and atomic
      vibrations in disordered materials has the universal functional form,
      C(omega)=A+Bomega(2), where the material-specific constants A and B are related
      to the distributions of fluctuating charges obeying global and local charge
      neutrality, respectively.

PMID- 17026114
TI  - Efficient calculation of electron diffraction for the structural determination of
      nanomaterials.
AB  - A critical advance in the technique of low-energy electron diffraction is
      presented and shown to enable determining detailed structures of nanomaterials,
      based on experimental methods that already exist or have been proposed. Our new
      cluster approach speeds up the computation to scale as n logn, rather than the
      current n3 or n2, with n the number of atoms, for example. Applications are
      illustrated for C60 molecules adsorbed on a Cu(111) surface, with and without
      coadsorbed metal atoms, exhibiting sensitivity to important structural features
      such as buckyball size and deformation.

PMID- 17026115
TI  - Interplay between diffusive and displacive phase transformations: time
      temperature-transformation diagrams and microstructures.
AB  - Materials which can undergo extremely fast displacive transformations as well as
      very slow diffusive transformations are studied using a Ginzburg-Landau
      framework. This simple model captures the essential physics behind microstructure
      formation and time-temperature-transformation diagrams in alloys such as steels.
      It also predicts the formation of mixed microstructures by an interplay between
      diffusive and displacive mechanisms. The intrinsic volume changes associated with
      the transformations stabilize mixed microstructures such as martensite-retained
      austenite (responsible for the existence of a martensite finish temperature) and
      martensite-pearlite.

PMID- 17026116
TI  - Fractional Stokes-Einstein and Debye-Stokes-Einstein relations in a network
      forming liquid.
AB  - We study the breakdown of the Stokes-Einstein (SE) and Debye-Stokes-Einstein
      (DSE) relations for translational and rotational motion in a prototypical model
      of a network-forming liquid, the ST2 model of water. We find that the emergence
      of fractional SE and DSE relations at low temperature is ubiquitous in this
      system, with exponents that vary little over a range of distinct physical
      regimes. We also show that the same fractional SE relation is obeyed by both
      mobile and immobile dynamical heterogeneities of the liquid.

PMID- 17026117
TI  - Exactly quantized dynamics of classical incommensurate sliders.
AB  - We report peculiar velocity quantization phenomena in the classical motion of an
      idealized 1D solid lubricant, consisting of a harmonic chain interposed between
      two periodic sliders. The ratio upsilon(c.m.)/upsilon(ext) of the chain center-of
      mass velocity to the externally imposed relative velocity of the sliders stays
      pinned to exact "plateau" values for wide ranges of parameters, such as slider
      corrugation amplitudes, external velocity, chain stiffness, and dissipation, and
      is strictly determined by the commensurability ratios alone. The phenomenon is
      explained by one slider rigidly dragging the kinks that the chain forms with the
      other slider. Possible consequences of these results for some real systems are
      discussed.

PMID- 17026118
TI  - Why N2 molecules with thermal energy abundantly dissociate on W(100) and not on
      W(110).
AB  - Low-energy N2 molecules easily dissociate on W(100) but not on W(110). In this
      Letter, the six-dimensional potential energy surface for the dissociation of N2
      molecules on W(110) has been determined by density functional calculations.
      Results are compared to those of N2 dissociation on W(100). The difference in
      reactivity between the two faces is shown to arise from the characteristics of
      the potential energy surface far from the surface (>3 A) and not from the
      properties of a precursor well or those of the final atomic adsorption sites.

PMID- 17026119
TI  - Carbon monoxide dissociation on Rh nanopyramids.
AB  - CO dissociation on rhomboidal faceted nanopyramids, produced on Rh(110) by fine
      tuning of ion irradiation conditions, has been studied by high resolution core
      level spectroscopy. We find that this morphology presents a large efficiency
      towards CO dissociation, a process which is inhibited on flat (110) terraces. We
      also measured the reactivity of nanostructures bound by different artificial step
      distributions identifying the sites responsible for the molecular bond disruption
      in the undercoordinated (n=6) edges running along the [11[over ]2] equivalent
      directions, with CO sitting in on-top configuration.

PMID- 17026120
TI  - Combinatorial search for optimal hydrogen-storage nanomaterials based on
      polymers.
AB  - We perform an extensive combinatorial search for optimal nanostructured hydrogen
      storage materials among various metal-decorated polymers using first-principles
      density-functional calculations. We take into account the zero-point vibration as
      well as the pressure- and temperature-dependent adsorption-desorption probability
      of hydrogen molecules. An optimal material we identify is Ti-decorated cis
      polyacetylene with reversibly usable gravimetric and volumetric density of 7.6 wt
      % and 63 kg/m(3), respectively, near ambient conditions. We also propose
      "thermodynamically usable hydrogen capacity" as a criterion for comparing
      different storage materials.

PMID- 17026121
TI  - Quasiparticlelike peaks, kinks, and electron-phonon coupling at the (pi,0)
      regions in the CMR oxide La2-2x Sr1+2x Mn2 O7.
AB  - Using angle-resolved photoemission, we have observed sharp quasiparticlelike
      peaks in the prototypical layered manganite La(2-2x)Sr(1+2x)Mn(2)O(7)
      (x=0.36,0.38). We focus on the (pi,0) regions of k space and study their
      electronic scattering rates and dispersion kinks, uncovering bilayer-split bands,
      the critical energy scales, momentum scales, and strengths of the interactions
      that renormalize the electrons. To identify these bosons, we measured phonon
      dispersions in the energy range of the kink by inelastic neutron scattering,
      finding a good match in both energy and momentum to the oxygen bond-stretching
      phonons.

PMID- 17026122
TI  - Synergistic polaron formation in the Hubbard-Holstein model at small doping.
AB  - We study the effect of dynamical Holstein phonons on the physics of the Hubbard
      model at small doping using the dynamical cluster approximation on a 2x2 cluster.
      Nonlocal antiferromagnetic correlations are found to significantly enhance the
      electron-phonon coupling, resulting in polaron formation for moderate coupling
      strengths. At finite doping, the electron-phonon coupling is found to strongly
      enhance the nonlocal spin correlations, indicating a synergistic interplay
      between the electron-phonon coupling and antiferromagnetic correlations. Although
      it enhances the pairing interaction, the electron-phonon coupling is found to
      decrease the superconducting transition temperature, due to the reduction in the
      quasiparticle fraction.

PMID- 17026123
TI  - Resonant x-ray diffraction studies on the charge ordering in magnetite.
AB  - Here we show that the low temperature phase of magnetite is associated with an
      effective, although fractional, ordering of the charge. Evidence and a
      quantitative evaluation of the atomic charges are achieved by using resonant x
      ray diffraction (RXD) experiments whose results are further analyzed with the
      help of ab initio calculations of the scattering factors involved. By confirming
      the results obtained from x-ray crystallography we have shown that RXD is able to
      probe quantitatively the electronic structure in very complex oxides, whose
      importance covers a wide domain of applications.

PMID- 17026124
TI  - Reversible tuning of the heavy-fermion ground state in CeCoIn5.
AB  - Cadmium doping the heavy-fermion superconductor CeCoIn(5) at the percent level
      acts as an electronic tuning agent, sensitively shifting the balance between
      superconductivity and antiferromagnetism and opening new ambient-pressure phase
      space in the study of heavy-fermion ground states.

PMID- 17026125
TI  - Quantum thermal conductance of electrons in a one-dimensional wire.
AB  - We use an electron thermometer to measure the temperature rise of approximately 2
      x 10(5) electrons in a two-dimensional box, due to heat flow into the box through
      a ballistic one-dimensional (1D) constriction. Using a simple model we deduce the
      thermal conductance kappa(Vg) of the 1D constriction, which we compare to its
      electrical conductance characteristics; for the first four 1D subbands the heat
      carried by the electrons passing through the wire is proportional to its
      electrical conductance G(Vg). In the vicinity of the 0.7 structure this
      proportionality breaks down, and a plateau at the quantum of thermal conductance
      pi(2)k(2/B)T/3h is observed.

PMID- 17026126
TI  - Electron spin dynamics in a self-assembled semiconductor quantum dot: the limit
      of low magnetic fields.
AB  - Using the trion as an optical probe, we uncover novel electron spin dynamics in
      CdSe/ZnSe Stranski-Krastanov quantum dots. The longitudinal spin lifetime obeys
      an inverse power law associated with recharging processes in the dot ensemble. No
      hint at spin-orbit mediated spin relaxation is found. At very weak magnetic
      fields (< 50 mT), electron spin dynamics related to the hyperfine interaction
      with the lattice nuclei is uncovered. A strong Knight field gives rise to nuclear
      ordering and formation of dynamical polarization on a 100-micros time scale under
      continuous electron spin pumping. The associated spin transients are temperature
      robust and can be observed up to 100 K.

PMID- 17026127
TI  - Effect of exchange interaction on spin dephasing in a double quantum dot.
AB  - We measure singlet-triplet dephasing in a two-electron double quantum dot in the
      presence of an exchange interaction which can be electrically tuned from much
      smaller to much larger than the hyperfine energy. Saturation of dephasing and
      damped oscillations of the spin correlator as a function of time are observed
      when the two interaction strengths are comparable. Both features of the data are
      compared with predictions from a quasistatic model of the hyperfine field.

PMID- 17026128
TI  - Lattice relaxation in oxide heterostructures: LaTiO3/SrTiO3 superlattices.
AB  - Local density approximation + Hubbard U and many-body effective Hamiltonian
      calculations are used to determine the effects of lattice relaxation in
      LaTiO3/SrTiO3 superlattices. Large ferroelectric-like distortions of the TiO6
      octahedra are found, which substantially affect the Ti d-electron density,
      bringing the calculated results into good agreement with experimental data. The
      relaxations also change the many-body physics, leading to a novel symmetry
      breaking-induced ordering of the xy orbitals, which does not occur in bulk
      LaTiO3, or in the hypothetical unrelaxed structure.

PMID- 17026129
TI  - Dephasing in (Ga,Mn)As nanowires and rings.
AB  - To understand quantum mechanical transport in a ferromagnetic semiconductor, the
      knowledge of basic material properties such as the phase coherence length and
      corresponding dephasing mechanism are indispensable ingredients. The lack of
      observable quantum phenomena has prevented experimental access to these
      quantities so far. Here we report the observations of universal conductance
      fluctuations in ferromagnetic (Ga,Mn)As. The analysis of the length and
      temperature dependence of the fluctuations reveals a T(-1) dependence of the
      dephasing time.

PMID- 17026130
TI  - Abelian and non-abelian Hall liquids and charge-density wave: quantum number
      fractionalization in one and two dimensions.
AB  - Previously, we have demonstrated that, on a torus, the Abelian quantum Hall
      liquid is adiabatically connected to a charge-density wave as the smaller
      dimension of the torus is varied. In this work, we extend this result to the non
      Abelian bosonic Hall state. The outcome of these works is the realization that
      the paradigms of quantum number fractionalization in one dimension
      (polyacetylene) and two dimensions (fractional quantum Hall effect) are, in fact,
      equivalent.

PMID- 17026131
TI  - Dynamics below the depinning threshold in disordered elastic systems.
AB  - We study the steady-state low-temperature dynamics of an elastic line in a
      disordered medium below the depinning threshold. Analogously to the equilibrium
      dynamics, in the limit T-->0, the steady state is dominated by a single
      configuration which is occupied with probability 1. We develop an exact algorithm
      to target this dominant configuration and to analyze its geometrical properties
      as a function of the driving force. The roughness exponent of the line at large
      scales is identical to the one at depinning. No length scale diverges in the
      steady-state regime as the depinning threshold is approached from below. We do
      find a divergent length, but it is associated only with the transient relaxation
      between metastable states.

PMID- 17026132
TI  - Fermi surface topology and the superconducting gap function in UPd2Al3: a neutron
      spin-echo study.
AB  - We report on a single crystal neutron spin-echo investigation of the low-energy
      dynamic response in the heavy-fermion superconductor UPd2Al3 in the vicinity of
      the antiferromagnetic wave vector Q(0)=(0 0 0.5). Well inside the superconducting
      phase, antiferromagnetic quasielastic scattering, which is present in the normal
      state, is absent for relaxation times up to 10 ns, equivalent to an energy
      resolution of approximately 1 microeV. This places strong constraints on possible
      models for this magnetic superconductor.

PMID- 17026133
TI  - Tunneling spectra of layered strongly correlated d-wave superconductors.
AB  - Tunneling conductance experiments on cuprate superconductors exhibit a large
      diversity of spectra that appear in different nanosized regions of inhomogeneous
      samples. In this Letter, we use a mean-field approach to the tt't''J model in
      order to address the features in these spectra that deviate from the BCS
      paradigm, namely, the bias sign asymmetry at high bias, the generic lack of
      evidence for the van Hove singularity, and the absence of coherence peaks at low
      dopings. We conclude that these features can be reproduced in homogeneous layered
      d-wave superconductors solely due to a proximate Mott insulating transition. We
      also establish the connection between the above tunneling spectral features and
      the strong renormalization of the electron dispersion around (0, pi) and (pi, 0)
      and the momentum space anisotropy of electronic states observed in angle-resolved
      photoemission spectroscopy experiments.

PMID- 17026134
TI  - Reentrant superconductivity in Nb/Cu1-xNix bilayers.
AB  - We report on the first observation of a pronounced reentrant superconductivity
      phenomenon in a superconductor/ferromagnet layered system. The results were
      obtained using a superconductor/ferromagnetic-alloy bilayer of Nb/Cu(1-x)Ni(x).
      The superconducting transition temperature T(c) drops sharply with increasing
      thickness dCuNi) of the ferromagnetic layer, until complete suppression of
      superconductivity is observed at d(CuNi) approximately equal to 4 nm. Increasing
      the Cu(1-x)Ni(x) layer thickness further, superconductivity reappears at d(CuNi)
      > or =13 nm. Our experiments give evidence for the pairing function oscillations
      associated with a realization of the quasi-one-dimensional Fulde-Ferrell-Larkin
      Ovchinnikov-like state in the ferromagnetic layer.

PMID- 17026135
TI  - Origin of nonlinear transport across the magnetically induced superconductor
      metal-insulator transition in two dimensions.
AB  - We have studied the effect of perpendicular magnetic fields and temperatures on
      nonlinear electronic transport in amorphous Ta superconducting thin films. The
      films exhibit a magnetic field-induced metallic behavior intervening the
      superconductor-insulator transition in the zero temperature limit. We show that
      the phase-identifying nonlinear transport in the superconducting and metallic
      phases arises from an intrinsic origin, not from an electron heating effect. The
      nonlinear transport is found to accompany an extraordinarily long voltage
      response time.

PMID- 17026136
TI  - End of aging in a complex system.
AB  - Aging phenomena in complex systems have been used as an important tool to
      investigate the physics of complexity. In particular, aging effects in spin
      glasses, measured using the thermoremanent magnetization decays, have been
      instrumental as a probe of complex equilibrium and nonequilibrium dynamics. In
      this Letter, we show that aging found in spin glass materials has a finite
      lifetime. After the aging part of the decay has ended, we find a post-aging decay
      which is apparently logarithmic in nature. This decay is independent of the
      waiting time and part of the same mechanism that produces aging.

PMID- 17026137
TI  - Dynamics of field-induced ordering in magnetic colloids studied by new time
      resolved small-angle neutron-scattering techniques.
AB  - The reversal of magnetic moments of nanoparticles in concentrated Co ferrofluids
      was monitored in an oscillating magnetic field by new time-resolved stroboscopic
      small-angle neutron-scattering techniques. Time resolution in the micros range
      was achieved by using a pulsed beam technique, TISANE, while in continuous mode
      resolution was limited by the wavelength spread to about 1 ms. The frequency
      dependence of anisotropic scattering patterns has been modeled using Langevin
      dynamics. The dynamics follows a two step mechanism: field-induced ordering is
      governed by fast Brownian rotation of nanoparticles with a characteristic time of
      about 160 micros. Magnetic relaxation of locally ordered domains of about 100 nm
      in size takes place within a few seconds by Brownian rotation or by Neel type
      rotation of magnetic moments.

PMID- 17026138
TI  - Nonlinear domain-wall velocity enhancement by spin-polarized electric current.
AB  - The interaction between a dc spin-polarized electric current and a magnetic
      domain wall in a Permalloy nanowire was studied by high-bandwidth scanning Kerr
      polarimetry. The full functional dependence of wall velocity on electric current
      and magnetic field is presented. With the pinning potential nulled by a field,
      current-induced velocity enhancements exceeded 35 m/s at a current density of
      approximately 6 x 10(11) A/m(2). This large enhancement, more than 10 times that
      found in pinning-dominated experiments, results in part from an interaction that
      is nonlinear in current and independent of current direction.

PMID- 17026139
TI  - Ultrafast dynamics of coherences in a quantum Hall system.
AB  - Using three-pulse four-wave-mixing optical spectroscopy, we study the ultrafast
      dynamics of the quantum Hall system. We observe striking differences as compared
      to an undoped system, where the 2D electron gas is absent. In particular, we
      observe a large off-resonant signal with strong oscillations. Using a microscopic
      theory, we show that these are due to many-particle coherences created by
      interactions between photoexcited carriers and collective excitations of the 2D
      electron gas. We extract quantitative information about the dephasing and
      interference of these coherences.

PMID- 17026140
TI  - Optical bistability in nonlinear surface-plasmon polaritonic crystals.
AB  - Nonlinear optical transmission through periodically nanostructured metal films
      (surface-plasmon polaritonic crystals) has been studied. The surface polaritonic
      crystals have been coated with a nonlinear polymer. The optical transmission of
      such nanostructures has been shown to depend on the control-light illumination
      conditions. The resonant transmission exhibits bistable behavior with the control
      light intensity. The bistability is different at different resonant signal
      wavelengths and for different wavelengths of the control light. The effect is
      explained by the strong sensitivity of the surface-plasmon mode resonances at the
      signal wavelength to the surrounding dielectric environment and the
      electromagnetic field enhancement due to plasmonic excitations at the controlled
      light wavelengths.

PMID- 17026141
TI  - Photoemission from buried interfaces in SrTiO3/LaTiO3 superlattices.
AB  - We have measured photoemission spectra of SrTiO3/LaTiO3 superlattices with a
      topmost SrTiO3 layer of variable thickness. A finite coherent spectral weight
      with a clear Fermi cutoff was observed at chemically abrupt SrTiO3/LaTiO3
      interfaces, indicating that an "electronic reconstruction" occurs at the
      interface between the Mott insulator LaTiO3 and the band insulator SrTiO3. For
      SrTiO3/LaTiO3 interfaces annealed at high temperatures (approximately 1000
      degrees C), which leads to Sr/La atomic interdiffusion and hence to the formation
      of La(1-x)Sr(x)TiO3-like material, the intensity of the incoherent part was found
      to be dramatically reduced whereas the coherent part with a sharp Fermi cutoff
      was enhanced due to the spread of charge. These important experimental features
      are well reproduced by layer dynamical-mean-field-theory calculation.

PMID- 17026143
TI  - Dynamics of a hard sphere granular impurity.
AB  - An impurity particle coupling to its host fluid via inelastic hard sphere
      collisions is considered. It is shown that the exact equation for its
      distribution function can be mapped onto that for an impurity with elastic
      collisions and an effective mass. The application of this result to the Enskog
      Lorentz kinetic equation leads to several conclusions: (1) every solution in the
      elastic case is equivalent to a class of solutions in the granular case; (2) for
      an equilibrium host fluid the granular impurity approaches equilibrium at a
      different temperature, with a dominant diffusive mode at long times; (3) for a
      granular host fluid in its scaling state, the granular impurity approaches the
      corresponding scaling solution.

PMID- 17026142
TI  - Glass transition of miscible binary polymer-polymer thin films.
AB  - The average glass transition temperatures, Tg, of thin homopolymer films exhibit
      a thickness dependence, Tg(h), associated with a confinement effect and with
      polymer-segment-interface interactions. The Tg's of completely miscible thin film
      blends of tetramethyl bisphenol-A polycarbonate (TMPC) and deuterated polystyrene
      (dPS), supported by SiO(x)/Si, decrease with decreasing h for PS weight fractions
      phi >0.1. This dependence is similar to that of PS and opposite to that of TMPC
      thin films. Based on an assessment of Tg(h, phi), we suggest that the Tg(h, phi)
      of miscible blends should be rationalized, additionally, in terms of the notion
      of a self-concentration and associated heterogeneous component dynamics.

PMID- 17026144
TI  - Direct measurement of torque in an optical trap and its application to double
      strand DNA.
AB  - We present a method that offers the possibility to directly apply and measure
      torque on particles in an optical trap. It can be used to rotationally manipulate
      biopolymers attached to appropriate particles. A flat object is trapped and
      oriented in the focus of a linearly polarized laser light. The direction and
      power of the orientational trap are controlled by the polarization state of the
      light. As a demonstration of the capabilities of the method, we examined the
      torsional stiffness of dsDNA (lambda-DNA) in its linear torsional regime by
      directly measuring the torque generated by the molecule.

PMID- 17026145
TI  - Force-induced desorption and unzipping of semiflexible polymers.
AB  - The thermally assisted force-induced desorption of semiflexible polymers from an
      adhesive surface or the unzipping of two bound semiflexible polymers by a
      localized force are investigated. The phase diagram in the force-temperature
      plane is calculated both analytically and by Monte Carlo simulations. Force
      induced desorption and unzipping of semiflexible polymers are first order phase
      transitions. A characteristic energy barrier for desorption is predicted, which
      scales with the square root of the polymer bending rigidity and governs the
      initial separation process before a plateau of constant separation force is
      reached. This leads to activated desorption and unzipping kinetics accessible in
      single molecule experiments.

PMID- 17026146
TI  - Comment on "Inseparability criteria for continuous bipartite quantum states".

PMID- 17026148
TI  - Comment on "Can one predict DNA transcription start sites by studying bubbles?".

PMID- 17026150
TI  - Self-localization of Bose-Einstein condensates in optical lattices via boundary
      dissipation.
AB  - We introduce a technique to obtain localization of Bose-Einstein condensates in
      optical lattices via boundary dissipations. Stationary and traveling localized
      states are generated by removing atoms at the optical lattice ends. Clear regimes
      of stretched-exponential decay for the number of atoms trapped in the lattice are
      identified. The phenomenon is universal and can also be observed in arrays of
      optical waveguides with mirrors at the system boundaries.

PMID- 17026151
TI  - Long-lived BLOCH oscillations with bosonic sr atoms and application to gravity
      measurement at the micrometer scale.
AB  - We report on the observation of Bloch oscillations on the unprecedented time
      scale of several seconds. The experiment is carried out with ultracold bosonic
      88Sr atoms loaded into a vertical optical standing wave. The negligible atom-atom
      elastic cross section and zero angular momentum in the ground state makes 88Sr an
      almost ideal Bose gas, insensitive to typical mechanisms of decoherence due to
      thermalization and external stray fields. The small size of the system enables
      precision measurements of forces at micrometer scale. This is a challenge in
      physics for studies of surfaces, Casimir effects, and searches for deviations
      from Newtonian gravity predicted by theories beyond the standard model.

PMID- 17026152
TI  - Formation of spatial shell structure in the superfluid to Mott insulator
      transition.
AB  - We report on the direct observation of the transition from a compressible
      superfluid to an incompressible Mott insulator by recording the in-trap density
      distribution of a Bosonic quantum gas in an optical lattice. Using spatially
      selective microwave transitions and spin-changing collisions, we are able to
      locally modify the spin state of the trapped quantum gas and record the spatial
      distribution of lattice sites with different filling factors. As the system
      evolves from a superfluid to a Mott insulator, we observe the formation of a
      distinct shell structure, in good agreement with theory.

PMID- 17026153
TI  - Master equation for a quantum particle in a gas.
AB  - The equation for the quantum motion of a Brownian particle in a gaseous
      environment is derived by means of S-matrix theory. This quantum version of the
      linear Boltzmann equation accounts nonperturbatively for the quantum effects of
      the scattering dynamics and describes decoherence and dissipation in a unified
      framework. As a completely positive master equation it incorporates both the
      known equation for an infinitely massive Brownian particle and the classical
      linear Boltzmann equation as limiting cases.

PMID- 17026154
TI  - Infrared imaging of single nanoparticles via strong field enhancement in a
      scanning nanogap.
AB  - We demonstrate nanoscale resolved infrared imaging of single nanoparticles
      employing near-field coupling in the nanoscopic gap between the metal tip of a
      scattering-type near-field optical microscope and the substrate supporting the
      particles. Experimental and theoretical evidence is provided that highly
      reflecting or polariton-resonant substrates strongly enhance the near-field
      optical particle contrast. Using Si substrates we succeeded in detecting Au
      particles as small as 8 nm (<lambda/1000) at midinfrared wavelengths of about
      lambda=10 microm. Our results open the door to infrared spectroscopy of
      individual nanoparticles, nanocrystals, or macromolecules.

PMID- 17026155
TI  - Dark energy as a Born-Infeld gauge interaction violating the equivalence
      principle.
AB  - We investigate the possibility that dark energy does not couple to gravitation in
      the same way as ordinary matter, yielding a violation of the weak and strong
      equivalence principles on cosmological scales. We build a transient mechanism in
      which gravitation is pushed away from general relativity by a Born-Infeld gauge
      interaction acting as an abnormally weighting (dark) energy. This mechanism
      accounts for the Hubble diagram of far-away supernovae by cosmic acceleration and
      time variation of the gravitational constant while accounting naturally for the
      present tests on general relativity.

PMID- 17026156
TI  - Irreducibility of the Weyl algebra in loop quantum gravity.
AB  - The irreducibility of the standard Weyl algebra representation in loop quantum
      gravity is proven using a very short and direct argument.

PMID- 17026157
TI  - Exploring Bd,s-->KK decays through flavor symmetries and QCD factorization.
AB  - We present a new analysis of Bd,s-->KK modes within the standard model (SM),
      relating them in a controlled way through SU(3)-flavor symmetry and QCD-improved
      factorization. We propose a set of sum rules for Bd,s-->K0K0 observables. We
      determine Bs-->KK branching ratios and CP asymmetries as functions of Adir(Bd-
      >K0K0), pointing out a conflict between BR(Bs-->K+K-) in the SM and data.
      Finally, we predict the amount of U-spin breaking between Bd-->pi+pi- and Bs-
      >K+K-.

PMID- 17026159
TI  - Top quark mediated Higgs boson decay into hadrons to order alphas5.
AB  - We present in analytic form the O(alphas5) correction to the H-->gg partial width
      of the standard-model Higgs boson with an intermediate mass MH<2Mt. Its knowledge
      is useful because the O(alphas4) correction is sizable (around 20%). For MH=120
      GeV, the resulting QCD correction factor reads
      1+(215/12)alphas(5)(MH)/pi+152.5[alphas(5)(MH)/pi]2+381.5[alphas(5)(MH)/pi]3
      approximately 1+0.65+0.20+0.02. The new four-loop correction increases the total
      Higgs-boson hadronic width by a small amount of order 1 per thousand and
      stabilizes significantly the residual scale dependence.

PMID- 17026162
TI  - piN-->etaN data require the existence of the N(1710) P11 resonance, reducing the
      1700-MeV continuum ambiguity.
AB  - In spite of long-lasting discussions, the agreement on the existence of the
      N(1710) P11 resonance has not yet been reached, so the Particle Data Group
      declares it as a 3-star resonance only. We show that the proper inclusion of
      inelastic channels in the coupled-channel formalism indisputably demands the
      existence of the N(1710) P11 state, and that it presumably stays hidden within
      the continuum ambiguity of a typical single-channel partial-wave analysis.
      Consequently, the Particle Data Group confidence rating of this state should be
      raised to a 4-star resonance.

PMID- 17026158
TI  - Evidence for B-->eta'pi and improved measurements for B-->eta'K.
AB  - We report evidence for the exclusive two-body charmless hadronic B meson decay B-
      >eta'pi, and improved measurements of B-->eta'K. The results are obtained from a
      data sample of 386x10(6) BB pairs collected at the Upsilon(4S) resonance, with
      the Belle detector at the KEKB asymmetric-energy e+e- collider. We measure B(B+-
      >eta'pi+)=[1.76(-0.62)(+0.67)(stat)(-0.14)(+0.15)(syst)]x10(-6) and B(B0-
      >eta'pi0)=[2.79(-0.96)(+1.02)(stat)(-0.34)(+0.25)(syst)]x10(-6). We also find the
      ratio of B(B+-->eta'K+)/B(B0-->eta'K0)=1.17+/-0.08(stat)+/-0.03(syst) and measure
      the direct CP asymmetries for the charged modes.

PMID- 17026160
TI  - Measurement of D0-->pilnu(Klnu) form factors and absolute branching fractions.
AB  - Using a 282 fb-1 data sample collected by the Belle experiment at the KEKB e+e-
      collider, we study D0 decays to K-l+nu and pi-l+nu final states. The D0 flavor
      and momentum are tagged through a full reconstruction of the recoiling charm
      meson and additional mesons from fragmentation. The reconstruction method
      provides very good resolution in neutrino momentum and in q2=(pl+pnu)2.
      Normalizing to the total number of D0 tags, we measure the absolute branching
      fractions to be B(D0-->Klnu)=(3.45+/-0.07stat+/-0.20syst)% and B(D0-
      >pilnu)=(0.255+/-0.019stat+/-0.016syst)% and the semileptonic form factors
      (within the modified pole model) f+K(0)=0.695+/-0.007stat+/-0.022syst and
      f+pi(0)=0.624+/-0.020stat+/-0.030syst.

PMID- 17026161
TI  - Observation of two new N* peaks in J/psi-->ppi-n and ppi+n decays.
AB  - The decay J/psi-->NNpi provides an effective isospin 1/2 filter for the piN
      system due to isospin conservation. Using 58x10(6) J/psi decays collected with
      the Beijing Electromagnetic Spectrometer at the Beijing Electron Positron
      Collider, more than 100 thousand J/psi-->ppi-n+c.c. events are obtained. Besides
      the two well-known N* peaks at around 1500 MeV/c2 and 1670 MeV/c2, there are two
      new, clear N* peaks in the ppi invariant mass spectrum around 1360 MeV/c2 and
      2030 MeV/c2 with statistical significance of 11sigma and 13sigma, respectively.
      We identify these as the first direct observation of the N*(1440) peak and a long
      sought missing N* peak above 2 GeV/c2 in the piN invariant mass spectrum.

PMID- 17026164
TI  - Effects of jet quenching on the hydrodynamical evolution of quark-gluon plasma.
AB  - We study the effects of jet quenching on the hydrodynamical evolution of the
      quark-gluon plasma (QGP) fluid created in a heavy-ion collision. In jet
      quenching, a hard QCD parton, before fragmenting into a jet of hadrons, deposits
      a fraction of its energy in the medium, leading to suppressed production of high
      pT hadrons. Assuming that the deposited energy quickly thermalizes, we simulate
      the subsequent hydrodynamic evolution of the QGP fluid. For partons moving at
      supersonic speed, vp>cs, and sufficiently large energy loss, a shock wave forms
      leading to conical flow. The PHENIX Collaboration recently suggested that
      observed structures in the azimuthal angle distribution might be caused by
      conical flow. We show here that, for phenomenologically acceptable values of
      parton energy loss, conical flow effects are too weak to explain these
      structures.

PMID- 17026165
TI  - Collectivity and configuration mixing in 186,188Pb and 194Po.
AB  - Lifetimes of prolate intruder states in 186Pb and oblate intruder states in 194Po
      have been determined by employing, for the first time, the recoil-decay tagging
      technique in recoil distance Doppler-shift lifetime measurements. In addition,
      lifetime measurements of prolate states in 188Pb up to the 8+ state were carried
      out using the recoil-gating method. The B(E2) values have been deduced from which
      deformation parameters |beta2|=0.29(5) and |beta2|=0.17(3) for the prolate and
      the oblate bands, respectively, have been extracted. The results also shed new
      light on the mixing between different shapes.

PMID- 17026166
TI  - Gamow-Teller strengths in the A = 14 multiplet: a challenge to the shell model.
AB  - A new experimental approach to the famous problem of the anomalously slow Gamow
      Teller (GT) transitions in the beta decay of the A=14 multiplet is presented. The
      GT strength distributions to excited states in 14C and 14O were studied in high
      resolution (d,2He) and (3He,t) charge-exchange reactions on 14N. No-core shell
      model calculations capable of reproducing the suppression of the beta decays
      predict a selective excitation of Jpi=2+ states. The experimental confirmation
      represents a validation of the assumptions about the underlying structure of the
      14N ground state wave function. However, the fragmentation of the GT strength
      over three 2+ final states remains a fundamental issue not explained by the
      present no-core shell model using a 6homega model space, suggesting possibly the
      need to include cluster structure in these light nuclei in a consistent way.

PMID- 17026167
TI  - Efimov states and their Fano resonances in a neutron-rich nucleus.
AB  - Asymmetric resonances in elastic n+19C scattering are attributed to Efimov states
      of such neutron-rich nuclei, that is, three-body bound states of the n+n+18C
      system when none of the pairs is bound or some of them are only weakly bound. By
      fitting to the general resonance shape described by Fano, we extract the
      resonance position, width, and the "Fano profile index." While Efimov states have
      been discussed extensively in many areas of physics, there is only one very
      recent experimental observation in trimers of cesium atoms. The conjunction that
      we present of the Efimov and Fano phenomena may lead to experimental realization
      in nuclei.

PMID- 17026168
TI  - Identification of mixed-symmetry states in an odd-mass nearly spherical nucleus.
AB  - The low-spin structure of 93Nb has been studied using the (n,n'gamma) reaction at
      neutron energies ranging from 1.5 to 3 MeV and the 94Zr(p,2ngamma)93Nb reaction
      at bombarding energies from 11.5 to 19 MeV. States at 1779.7 and 1840.6 keV,
      respectively, are proposed as mixed-symmetry states associated with the pi2p(1/2)
      1x(2(1),MS+,94Mo) coupling. These assignments are derived from the observed M1
      and E2 transition strengths to the 2p(1/2)-1x(2(1)+,94Mo) symmetric one-phonon
      states, energy systematics, spins and parities, and comparison with shell model
      calculations.

PMID- 17026169
TI  - Proposal for a sensitive search for the electric dipole moment of the electron
      with matrix-isolated radicals.
AB  - We propose using matrix-isolated paramagnetic diatomic molecules to search for
      the electric dipole moment of the electron (eEDM). As was suggested by Shapiro in
      1968, the eEDM leads to a magnetization of a sample in the external electric
      field. In a typical condensed matter experiment, the effective field on the
      unpaired electron is of the same order of magnitude as the laboratory field,
      typically about 10(5) V/cm. We exploit the fact that the effective electric field
      inside heavy polar molecules is on the order of 10(10) V/cm. This leads to a huge
      enhancement of the Shapiro effect. Statistical sensitivity of the proposed
      experiment may allow one to improve the current limit on eEDM by 3 orders of
      magnitude in a few hours accumulation time.

PMID- 17026170
TI  - Large cross-phase modulation between slow copropagating weak pulses in 87Rb.
AB  - We propose a scheme to generate double electromagnetically induced transparency
      and optimal cross-phase modulation for two slow, copropagating pulses with
      matched group velocities in a single species of atom, namely 87Rb. A single pump
      laser is employed and a homogeneous magnetic field is utilized to avoid
      cancellation effects through the nonlinear Zeeman effect. We suggest a feasible
      preparational procedure for the atomic initial state to achieve matched group
      velocities for both signal fields.

PMID- 17026171
TI  - Coalescence of spreading droplets on a wettable substrate.
AB  - We investigate experimentally and theoretically the coalescence dynamics of two
      spreading droplets on a highly wettable substrate. Upon contact, surface tension
      drives a rapid motion perpendicular to the line of centers that joins the drops
      and lowers the total surface area. We find that the width of the growing meniscus
      bridge between the two droplets exhibits power-law behavior, growing at early
      times as t1/2. Moreover, the growth rate is highly sensitive to both the radii
      and heights of the droplets at contact, scaling as ho3/2/Ro. This size dependence
      differs significantly from the behavior of freely suspended droplets, in which
      the coalescence growth rate depends only weakly on the droplet size. We
      demonstrate that the scaling behavior is consistent with a model in which the
      growth of the meniscus bridge is governed by the viscously hindered flux from the
      droplets.

PMID- 17026172
TI  - Order-chaos-order transitions in electrosprays: the electrified dripping faucet.
AB  - Electrosprays have diverse applications including protein analysis,
      electrospinning, and nanoencapsulation for drug delivery. We show that a variety
      of electrospray regimes exhibit fundamental analogy with the nonlinear dynamics
      of a dripping faucet. The applied voltage in electrosprays results in additional
      period doublings and temporal order-chaos-order transitions. Attractors in the
      return maps show logarithmic self-similarity in time, suggesting self-similar
      capillary waves on the meniscus. The bifurcations in ejection time can be
      explained by phase variations between capillary waves and pinch-off conditions
      and by ejection mode changes due to contact angle variations.

PMID- 17026173
TI  - Geometric simulation of perovskite frameworks with Jahn-Teller distortions:
      applications to the cubic manganites.
AB  - A new approach is presented for modeling perovskite frameworks with disordered
      Jahn-Teller (JT) distortions and has been applied to study the elastic response
      of the LaMnO3 structure to defects in the JT ordering. Surprisingly, antiphase
      domain boundary defects in the pattern of ordered JT octahedra, along the [110]
      and [110] bonding directions, are found to produce 1D stripe patterns rotated 45
      degrees along a* directions, similar to stripe structures observed in these
      systems. Geometric simulation is shown to be an efficient and powerful approach
      for finding relaxed atomic structures in the presence of disorder in networks of
      corner-shared JT-distorted octahedra such as the perovskites. Geometric modeling
      rapidly relaxes large supercells (thousands of octahedra) while preserving the
      local coordination chemistry, and shows great promise for studying these complex
      systems.

PMID- 17026174
TI  - Cooperative shear model for the rheology of glass-forming metallic liquids.
AB  - A rheological law based on the concept of cooperatively sheared flow zones is
      presented, in which the effective thermodynamic state variable controlling flow
      is identified to be the isoconfigurational shear modulus of the liquid. The law
      captures Newtonian as well as non-Newtonian viscosity data for glass-forming
      metallic liquids over a broad range of fragility. Acoustic measurements on
      specimens deformed at a constant strain rate correlate well with the measured
      steady-state viscosities, hence verifying that viscosity has a unique functional
      relationship with the isoconfigurational shear modulus.

PMID- 17026175
TI  - Heterogeneous nucleation in and out of pores.
AB  - We study the nucleation of a new thermodynamic phase in pores and find that the
      nucleation often proceeds via two steps: nucleation of pore filling, and
      nucleation out of the pore. These two rates have opposing dependencies on pore
      size, resulting in a pore size at which the nucleation rate of the new phase is
      maximal. This finding is relevant to attempts to design and use porous media to
      crystallize proteins.

PMID- 17026176
TI  - Two-dimensional Ising model criticality in a three-dimensional uniaxial relaxor
      ferroelectric with frozen polar nanoregions.
AB  - The charge-disordered three-dimensional uniaxial relaxor ferroelectric
      Sr0.61Ba0.39Nb2O6 splits up into metastable polar nanoregions and paraelectric
      interfaces upon cooling from above Tc. The frozen polar nanoregions are verified
      by piezoresponse force microscopy, respond domainlike to dynamic light scattering
      and dielectric excitation, reveal nonergodicity at T>Tc via global aging, and
      coalesce into polar nanodomains below Tc. Contrastingly, the percolating system
      of unperturbed interfaces becomes ferroelectric with two-dimensional Ising-model
      like critical exponents alpha=0, beta=1/8, and gamma=7/4, as corroborated by ac
      calorimetry, second harmonic generation, and susceptometry, respectively.

PMID- 17026163
TI  - Measurement of the Bs0-Bs0 oscillation frequency.
AB  - We present the first precise measurement of the Bs0-Bs0 oscillation frequency
      Deltams. We use 1 fb-1 of data from pp collisions at sqrts=1.96 TeV collected
      with the CDF II detector at the Fermilab Tevatron. The sample contains signals of
      3600 fully reconstructed hadronic Bs decays and 37,000 partially reconstructed
      semileptonic Bs decays. We measure the probability as a function of proper decay
      time that the Bs decays with the same, or opposite, flavor as the flavor at
      production, and we find a signal consistent with Bs0-Bs0 oscillations. The
      probability that random fluctuations could produce a comparable signal is 0.2%.
      Under the hypothesis that the signal is due to Bs0-Bs0 oscillations, we measure
      Deltams=17.31(-0.18)+0.33(stat)+/-0.07(syst) ps-1 and determine |Vtd/Vts|=0.208(
      0.002)+0.001(expt)-0.006(+0.008)(theor).

PMID- 17026177
TI  - Collapse of transient nucleation fluxes in a cold Ising ferromagnet.
AB  - We report the time-dependent nucleation fluxes and associated nucleation rates in
      a metastable Ising ferromagnet on square lattice with Metropolis (Glauber-type)
      dynamics. It is discovered that, with lowering of the temperature, fluxes
      collapse into several representative transient curves corresponding to magic
      cluster sizes. Those can be associated with physical droplets, i.e., long-lived
      configurations which provide a link with the classical Becker-Doring picture.

PMID- 17026178
TI  - From ultraslow to fast lithium diffusion in the 2D ion conductor Li0.7TiS2 probed
      directly by stimulated-echo NMR and nuclear magnetic relaxation.
AB  - 7Li stimulated-echo NMR and classical relaxation NMR techniques are jointly used
      for the first time for a comprehensive investigation of Li diffusion in layer
      structured Li0.7TiS2. One single 2D Li diffusion process was probed over a
      dynamic range of almost 10 orders of magnitude. So far, this is the largest
      dynamic range being measured by 7Li NMR spectroscopy directly, i.e., without the
      help of a specific theoretical model. The jump rates obey a strict Arrhenius law,
      determined by an activation energy of 0.41(1) eV and a preexponential factor of
      6.3(1)x10(12) s-1, and range between 1x10(-1) s-1 and 7.8x10(8) s-1 (148-510 K).
      Ultraslow Li jumps in the kHz to sub-Hz range were measured directly by recording
      7Li spin-alignment correlation functions. The temperature and, in particular, the
      frequency dependence of the relaxation rates fully agree with results expected
      for 2D diffusion.

PMID- 17026179
TI  - Structure and interconversion of oxygen-vacancy-related defects on amorphous
      silica.
AB  - Atomic structure and structural stability of neutral oxygen vacancies on
      amorphous silica are investigated using combined Monte Carlo and density
      functional calculations. We find that, unlike their bulk counterparts, the Si-Si
      dimer configuration of surface oxygen vacancies is likely to be unstable due to
      the high tensile strains induced, thereby undergoing thermally activated
      transformation with a moderate barrier into other stable configurations including
      dicoordinated silicon, silanone, or a subsurface Si-Si dimer, depending on the
      local surface structure. Pathways for the interconversion between these oxygen
      vacancy-related defects are presented with a discussion of their viability.

PMID- 17026180
TI  - Crossover from stretched to compressed exponential relaxations in a polymer-based
      sponge phase.
AB  - X-ray photon correlation spectroscopy was used to characterize the wave vector-
      and temperature-dependent dynamics of spontaneous thermal fluctuations in a
      sponge (L3) phase that occurs in a blend of a symmetric poly(styrene
      ethylene/butylene-styrene) triblock copolymer with a polystyrene homopolymer.
      Measurements of the intermediate scattering function reveal a crossover from
      stretched- to compressed-exponential relaxations as the temperature is lowered
      from 180 to 120 degrees C.

PMID- 17026181
TI  - Symmetric liquid-liquid interface with a nonzero spontaneous curvature.
AB  - The curvature dependence of the symmetric interface between two immiscible
      polymer solutions in a common monomeric solvent is analyzed using a self
      consistent field theory. Contrary to symmetry arguments we find that the surface
      tension depends in first order on a nonzero Tolman length. These interfaces
      further have a negative mean and a positive Gaussian bending modulus. The finite
      spontaneous curvature is attributed to the adsorption of the solvent at the
      interface.

PMID- 17026182
TI  - Mott transition in kagome lattice Hubbard model.
AB  - We investigate the Mott transition in the kagome lattice Hubbard model using a
      cluster extension of dynamical mean field theory. The calculation of the double
      occupancy, the density of states, and the static and dynamical spin correlation
      functions demonstrates that the system undergoes the first-order Mott transition
      at the Hubbard interaction U/W approximately 1.4 (W:bandwidth). In the metallic
      phase close to the Mott transition, we find the strong renormalization of three
      distinct bands, giving rise to the formation of heavy quasiparticles with strong
      frustrated interactions. It is elucidated that the quasiparticle states exhibit
      anomalous behavior in the temperature-dependent spin correlation functions.

PMID- 17026183
TI  - Polarization and propagation of polariton condensates.
AB  - With the use of the generalized Gross-Pitaevskii equation it is shown that
      exciton polaritons in semiconductor microcavities form a linearly polarized
      condensate having two branches of the excitation spectrum. The splitting between
      these branches is strongly anisotropic. This anisotropy noticeably affects the
      real-space dynamics of polariton condensates.

PMID- 17026184
TI  - Spin-Hall conductivity in electron-phonon coupled systems.
AB  - We derive the ac spin-Hall conductivity sigmasH(omega) of two-dimensional spin
      orbit coupled systems interacting with dispersionless phonons of frequency
      omega0. For the linear Rashba model, we show that the electron-phonon
      contribution to the spin-vertex corrections breaks the universality of
      sigmasH(omega) at low frequencies and provides a nontrivial renormalization of
      the interband resonance. On the contrary, in a generalized Rashba model for which
      the spin-vertex contributions are absent, the coupling to the phonons enters only
      through the self-energy, leaving the low-frequency behavior of sigmasH(omega)
      unaffected by the electron-phonon interaction.

PMID- 17026185
TI  - Electrically detected electron spin resonance in a high-mobility silicon quantum
      well.
AB  - The resistivity change due to electron spin resonance (ESR) absorption is
      investigated in a high-mobility two-dimensional electron system formed in a
      Si/SiGe heterostructure. Results for a specific Landau level configuration
      demonstrate that the primary cause of the ESR signal is a reduction of the spin
      polarization, not the effect of electron heating. The longitudinal spin
      relaxation time T1 is obtained to be of the order of 1 ms in an in-plane magnetic
      field of 3.55 T. The suppression of the effect of the Rashba fields due to high
      frequency spin precession explains the very long T1.

PMID- 17026187
TI  - Positive current correlations associated with super-Poissonian shot noise.
AB  - We report on shot noise cross spectrum measurements in a beam splitter
      configuration. Electrons tunneling through potential barriers are incident on a
      beam splitter and scattered into two separate channels. Such a partition process
      introduces correlations between the fluctuations of the two currents. Our work
      has confirmed that the generally expected negative correlations resulted from sub
      Poissonian electron sources. More interestingly, positive cross correlations
      associated with barriers exhibiting super-Poissonian shot noise have also been
      observed. We have found that both positive and negative correlations can be
      related to the noise properties of the electron source.

PMID- 17026186
TI  - Universal spin-Hall conductance fluctuations in two dimensions.
AB  - We report a theoretical investigation on spin-Hall conductance fluctuation of
      disordered four-terminal devices in the presence of Rashba or/and Dresselhaus
      spin-orbital interactions in two dimensions. As a function of disorder, the spin
      Hall conductance GsH shows ballistic, diffusive, and insulating transport
      regimes. For given spin-orbit interactions, a universal spin-Hall conductance
      fluctuation (USCF) is found in the diffusive regime. The value of the USCF
      depends on the spin-orbit coupling tso but is independent of other system
      parameters. It is also independent of whether Rashba or Dresselhaus or both spin
      orbital interactions are present. When tso is comparable to the hopping energy t,
      the USCF is a universal number approximately 0.18e/4pi. The distribution of GsH
      crosses over from a Gaussian distribution in the metallic regime to a non
      Gaussian distribution in the insulating regime as the disorder strength is
      increased.

PMID- 17026188
TI  - Full-counting statistics for voltage and dephasing probes.
AB  - We present a stochastic path integral method to calculate the full-counting
      statistics of conductors with energy conserving dephasing probes and dissipative
      voltage probes. The approach is explained for the experimentally important case
      of a Mach-Zehnder interferometer, but is easily generalized to more complicated
      setups. For all geometries where dephasing may be modeled by a single one-channel
      dephasing probe we prove that our method yields the same full-counting statistics
      as phase averaging of the cumulant generating function.

PMID- 17026189
TI  - Fluctuation-exchange study of antiferromagnetism in disordered electron-doped
      cuprate superconductors.
AB  - On the basis of the Hubbard model, we extend the fluctuation-exchange (FLEX)
      approach to investigating the properties of the antiferromagnetic (AF) phase in
      electron-doped cuprate superconductors. Furthermore, by incorporating the effect
      of scatterings due to the disordered dopant atoms into the FLEX formalism, our
      numerical results show that the antiferromagnetic transition temperature, the
      onset temperature of pseudogap due to spin fluctuations, the spectral density of
      the single particle near the Fermi surface, and the staggered magnetization in
      the AF phase as a function of electron doping can consistently account for the
      experimental measurements.

PMID- 17026190
TI  - Orbital ordering and Jahn-Teller distortion in Perovskite ruthenate SrRuO3.
AB  - Local density approximation plus on-site Coulomb interaction U band structure
      calculations reveal that SrRuO3 exhibits a half-metallic ground state with an
      integer spin moment of 2.0 microB/SrRuO3. An associated tilting 4dt2g orbital
      ordering on a Ru sublattice is observed under the on-site Coulomb interaction U
      in the presence of lattice distortion. This finding unravels the on-site Coulomb
      correlation as the driving force of the 4d orbital ordering and Jahn-Teller
      distortion as well as of the half-metallic ground state.

PMID- 17026191
TI  - Flux-flow resistivity anisotropy in the instability regime of the a-b plane of
      epitaxial superconducting YBa2Cu3O7-delta thin films.
AB  - Measurements of the nonlinear flux-flow resistivity rho and the critical vortex
      velocity vphi* at high voltage bias close to the instability regime predicted by
      Larkin and Ovchinnikov (Z. Eksp. Teor. Fiz 68, 1915 (1975) [Sov. Phys. JETP 41,
      960 (1976)]) are reported along the node and antinode directions of the d-wave
      order parameter in the a-b plane of epitaxial YBa2Cu3O7-delta films. In this
      pinning-free regime, rho and vphi* are found to be anisotropic with values in the
      node direction larger on average by 10% than in the antinode direction. The
      anisotropy of rho is almost independent of temperature and field. We attribute
      the observed results to the anisotropic quasiparticle distribution on the Fermi
      surface of YBa2Cu3O7-delta.

PMID- 17026192
TI  - Spectrum of the Andreev billiard and giant fluctuations of the Ehrenfest time.
AB  - The density of states in the semiclassical Andreev billiard is theoretically
      studied and shown to be determined by the fluctuations of the classical Lyapunov
      exponent lambda. The rare trajectories with a small value of lambda give rise to
      an anomalous increase of the Ehrenfest time tauE approximately |lnvariant
      Planck's over 2pi|/lambda and, consequently, to the appearance of Andreev levels
      with small excitation energy. The gap in spectrum is obtained, and fluctuations
      of the value of the gap due to different positions of superconducting lead are
      considered.

PMID- 17026193
TI  - Thermal conductivity in the vicinity of the quantum critical end point in
      Sr3Ru2O7.
AB  - Thermal conductivity of Sr3Ru2O7 was measured down to 40 mK and at magnetic
      fields through the quantum critical end point at Hc=7.85 T. A peak in the
      electrical resistivity as a function of the field was mimicked by the thermal
      resistivity. In the limit as T-->0 K, we find that the Wiedemann-Franz law is
      satisfied to within 5% at all fields, implying that there is no breakdown of the
      electron despite the destruction of the Fermi liquid state at quantum
      criticality. A significant change in disorder [from rho0(H=0 T)=2.1 to 0.5
      microOmega cm] does not influence our conclusions. At finite temperatures, the
      temperature dependence of the Lorenz number is consistent with ferromagnetic
      fluctuations causing the non-Fermi liquid behavior as one would expect at a
      metamagnetic quantum critical end point.

PMID- 17026194
TI  - Superconducting atomic contacts under microwave irradiation.
AB  - We have measured the effect of microwave irradiation on the dc current-voltage
      characteristics of superconducting atomic contacts. The interaction of the
      external field with the ac supercurrents leads to replicas of the supercurrent
      peak, the well-known Shapiro resonances. The observation of supplementary
      fractional resonances for contacts containing highly transmitting conduction
      channels reveals their nonsinusoidal current-phase relation. The resonances sit
      on a background current which is itself deeply modified, as a result of photon
      assisted multiple Andreev reflections. The results provide firm support for the
      full quantum theory of transport between two superconductors based on the concept
      of Andreev bound states.

PMID- 17026195
TI  - Specular Andreev reflection in graphene.
AB  - By combining the Dirac equation of relativistic quantum mechanics with the
      Bogoliubov-de Gennes equation of superconductivity we investigate the electron
      hole conversion at a normal-metal-superconductor interface in graphene. We find
      that the Andreev reflection of Dirac fermions has several unusual features: (1)
      the electron and hole occupy different valleys of the band structure; (2) at
      normal incidence the electron-hole conversion happens with unit efficiency in
      spite of the large mismatch in Fermi wavelengths at the two sides of the
      interface; and, most fundamentally: (3) away from normal incidence the reflection
      angle may be the same as the angle of incidence (retroreflection) or it may be
      inverted (specular reflection). Specular Andreev reflection dominates in weakly
      doped graphene, when the Fermi wavelength in the normal region is large compared
      to the superconducting coherence length.

PMID- 17026196
TI  - Imprinting vortices into antiferromagnets.
AB  - The effect of imprinting symmetric and displaced vortex structures into an
      antiferromagnetic material is investigated in micron-sized disks consisting of
      exchange coupled ferromagnetic-antiferromagnetic bilayers. The imprint of
      displaced vortices manifests itself by the occurrence of a new type of asymmetric
      hysteresis loops characterized by curved, reversible, central sections with
      nonzero remanent magnetization. Such an imprint is achieved by cooling the disks
      through the blocking temperature of the system in small fields. Micromagnetic
      simulations reveal that asymmetric vortexlike loops naturally result from the
      competition between the different energies involved in the system.

PMID- 17026197
TI  - Spin nematics and magnetization plateau transition in anisotropic kagome magnets.
AB  - We study S=1 kagome antiferromagnets with an isotropic Heisenberg exchange J and
      strong easy-axis single-ion anisotropy D. For D>>J, the low-energy physics can be
      described by an effective S=1/2 XXZ model with antiferromagnetic Jz approximately
      J and ferromagnetic J perpendicular approximately J2/D. Exploiting this
      connection, we argue that nontrivial ordering into a "spin-nematic" occurs
      whenever D dominates over J, and discuss its experimental signatures. We also
      study a magnetic field induced transition to a magnetization plateau state at
      magnetization 1/3 which breaks lattice translation symmetry due to ordering of
      the Sz and occupies a lobe in the B/Jz-Jz/J perpendicular phase diagram.

PMID- 17026198
TI  - Magnetocrystalline anisotropy in permalloy revisited.
AB  - Permalloy with a body-centered-cubic structure has been grown on GaAs(001) by
      molecular beam epitaxy. Its magnetism, Curie temperature, and magnetic anisotropy
      are determined experimentally and compared to those of conventional face-centered
      cubic Permalloy. Unexpectedly the vanishing magnetic cubic anisotropy in
      Permalloy is found to be independent of its atomic structure but depends only
      upon the stoichiometry of Fe and Ni in the FexNi1-x alloy. This observation is
      further investigated and confirmed by first-principles electronic band
      calculations, which help to understand the long-standing issue of why Permalloy
      should be a soft magnet.

PMID- 17026199
TI  - Elastic domains in antiferromagnets on substrates.
AB  - We consider periodic domain structures which appear due to the magnetoelastic
      interaction if the antiferromagnetic crystal is attached to an elastic substrate.
      The peculiar behavior of such structures in an external magnetic field is
      discussed. In particular, we find the magnetic field dependence of the
      equilibrium period and the concentrations of different domains.

PMID- 17026200
TI  - Giant spin-orbit bowing in GaAs1-xBix.
AB  - We report a giant bowing of the spin-orbit splitting energy Delta0 in the dilute
      GaAs1-xBix alloy for Bi concentrations ranging from 0% to 1.8%. This is the first
      observation of a large relativistic correction to the host electronic band
      structure induced by just a few percent of isoelectronic doping in a
      semiconductor material. It opens up the possibility of tailoring the spin-orbit
      splitting in semiconductors for spintronic applications.

PMID- 17026201
TI  - Spin-lattice interaction in the quasi-one-dimensional helimagnet LiCu2O2.
AB  - The field dependence of the electron spin resonance in a helimagnet LiCu2O2 was
      investigated for the first time. In the paramagnetic state, a broad resonance
      line was observed corresponding to a g factor of 2.3. In the critical regime,
      around the paramagnetic to helimagnetic phase transition the resonance broadens
      and shifts to higher frequencies. A narrow signal is recovered at a low
      temperature, corresponding to a spin gap of 1.4 meV in zero field. A
      comprehensive model of the magnons is presented, using exchange parameters from
      neutron scattering [T. Masuda Phys. Rev. B 72, 014405
      (2005)10.1103/PhysRevB.72.014405] and the spin anisotropy determined here. The
      role of the quantum fluctuations is discussed.

PMID- 17026202
TI  - Mechanism of carrier photogeneration and carrier transport in molecular crystal
      tetracene.
AB  - Models for the carrier photoexcitation mechanism in molecular crystals have been
      established initially on the bases of measurements on oligoacenes and later
      applied to conjugated polymers as well. These models emphasize the localized
      nature of photoexcitations and describe carrier generation as a secondary process
      involving exciton dissociation. The results of our photoconductivity studies of
      single crystal tetracene are at variance with these widely accepted models, and
      in fact indicate that the photocarrier quantum efficiency appears independent of
      temperature, photon energy, and light intensity, thus featuring the hallmarks of
      direct interband carrier photogeneration and coherent carrier transport at band
      states.

PMID- 17026203
TI  - Time evolution of the electronic structure of 1T-TaS2 through the insulator-metal
      transition.
AB  - Femtosecond time-resolved photoemission is used to investigate the time evolution
      of electronic structure in the Mott insulator 1T-TaS2. A collapse of the
      electronic gap is observed within 100 femtoseconds after optical excitation. The
      photoemission spectra and the spectral function calculated by dynamical mean
      field theory show that this insulator-metal transition is driven solely by hot
      electrons. A coherently excited lattice displacement results in a periodic shift
      of the spectra lasting for 20 ps without perturbing the insulating phase. This
      capability to disentangle electronic and phononic excitations opens new
      directions to study electron correlation in solids.

PMID- 17026204
TI  - Trapped electromagnetic modes and scaling in the transmittance of perforated
      metal films.
AB  - We describe measurements and simulations of the enhanced transmittance by
      subwavelength hole arrays in silver films. The array period and hole size are
      systematically varied to give peak transmittances at wavelengths spanning a
      factor of 14. The spectra coincide when scaled using the array geometry and
      substrate refractive index alone, thus showing no significant dependence on the
      dielectric function of the metal. We argue that the spectra can be explained by
      interference of diffractive and resonant scattering. The resonant contribution
      comes from electromagnetic modes trapped in the film vicinity.

PMID- 17026205
TI  - Polymer-population mapping and localization in the space of phenotypes.
AB  - We present a mapping between the thermodynamics of an ideal heteropolymer in an
      external field and the dynamics of structured populations in fluctuating
      environments. We employ a population model in which individuals may adopt
      different phenotypes, each of which may be optimal in a different environment.
      Using this mapping, we develop a path integral formulation for populations and
      predict the existence of a biological counterpart for the well-known
      heteropolymer localization phase transition.

PMID- 17026206
TI  - Signal detection, modularity, and the correlation between extrinsic and intrinsic
      noise in biochemical networks.
AB  - We present an expression for the power spectrum of the output signal of a
      biochemical network, which reveals that the reactions that allow a network to
      detect biochemical signals, induce correlations between the extrinsic noise of
      the input signals and the intrinsic noise of the reactions that form the network.
      We show that anticorrelations between the extrinsic and intrinsic noise enhance
      the robustness of zero-order ultrasensitive networks to biochemical noise. We
      discuss the consequences for a modular description of noise transmission using
      the mitogen-activated protein kinase cascade.

PMID- 17026207
TI  - Solubility and charge inversion of complexes of DNA and basic proteins.
AB  - The basic proteins, protamines and histones H1, are known to condense DNA in
      vivo. We examine here their ability to condense and solubilize in vitro linear
      DNA [and a synthetic polyanion, Poly(Styrene-Sulfonate) or PSS] at low ionic
      concentrations by varying the charge concentration ratio. Phase separation is
      observed in a very narrow range of ratios for short DNA and PSS; on both sides of
      this range, polydisperse and charged complexes are formed. A charge inversion is
      detected. For long DNA chains however, a different behavior is observed: the
      complexes are not soluble in excess of proteins.

PMID- 17026208
TI  - Filamin cross-linked semiflexible networks: fragility under strain.
AB  - The semiflexible F-actin network of the cytoskeleton is cross-linked by a variety
      of proteins including filamin, which contains Ig domains that unfold under
      applied tension. We examine a simple filament network model cross-linked by such
      unfolding linkers that captures the main mechanical features of F-actin networks
      cross-linked by filamin proteins and show that, under sufficient strain, the
      network spontaneously self-organizes so that an appreciable fraction of the
      filamin cross-linkers are at the threshold of domain unfolding. We propose and
      test a mean-field model to account for this effect. We also suggest a qualitative
      experimental signature of this type of network reorganization under applied
      strain that may be observable in intracellular microrheology experiments of
      Crocker et al.

PMID- 17026209
TI  - Snake's perspective on heat: reconstruction of input using an imperfect detection
      system.
AB  - Two groups of snakes possess an infrared detection system that is used to create
      a heat image of their environment. In this Letter we present an explicit
      reconstruction model, the "virtual lens," which explains how a snake can overcome
      the optical limitations of a wide aperture pinhole camera, and how ensuing
      properties of the receptive fields on the infrared-sensitive membrane may explain
      the behavioral performance of this sensory system. Our model explores the optical
      quality of the infrared system by detailing how a functional representation of
      the thermal properties of the environment can be created. The model is easy to
      implement neuronally and agrees well with available neuronal, physiological, and
      behavioral data on the snake infrared system.

PMID- 17026210
TI  - Kinetics of the Wako-Saito-Munoz-Eaton model of protein folding.
AB  - We consider a simplified model of protein folding, with binary degrees of
      freedom, whose equilibrium thermodynamics is exactly solvable. Based on this
      exact solution, the kinetics is studied in the framework of a local equilibrium
      approach, for which we prove that (i) the free energy decreases with time, (ii)
      the exact equilibrium is recovered in the infinite time limit, and (iii) the
      equilibration rate is an upper bound of the exact one. The kinetics is compared
      to the exact one for a small peptide and to Monte Carlo simulations for a longer
      protein; then rates are studied for a real protein and a model structure.

PMID- 17026211
TI  - Long-range depletion forces induced by associating small molecules.
AB  - This is the first report of experimental observations of depletion interactions
      in solutions of a (hydrogen-bonded) reversible supramolecular polymer. Depletion
      forces were measured directly by colloidal probe atomic force microscopy. The
      range of the depletion force is consistent with existing independent experimental
      data. The interaction can be tuned by adding monofunctional chain stoppers to the
      solution, a possibility which is unique to supramolecular polymers. The depletion
      force is shown to be strong enough to induce phase separation in a colloidal
      suspension.

PMID- 17026212
TI  - Repulsion between oppositely charged surfaces in multivalent electrolytes.
AB  - In answer to recent experimental force measurements between oppositely charged
      surfaces we here reproduce the repulsion in the presence of multivalent salt
      using Monte Carlo simulations within the primitive model. Our osmotic pressure
      curves are in good agreement with experimental results. In contrast with Poisson
      Boltzmann calculations, both repulsion and charge inversion are seen in the
      simulations. Repulsion is observed only for conditions under which there is
      charge inversion at large separations. However, in these cases, the repulsion is
      present also at intermediate separations, where there is no charge inversion. The
      charge inversion is thereby not the cause of the repulsion. Instead the repulsion
      appears to be an effect of the large amount of excess salt in the slit. Both
      phenomena, however, are closely linked and a consequence of ion-ion correlations,
      promoted by a strong electrostatic coupling.

PMID- 17026213
TI  - Spin decoherence in superconducting atom chips.
AB  - Using a consistent quantum-mechanical treatment for the electromagnetic
      radiation, we theoretically investigate the magnetic spin-flip scatterings of a
      neutral two-level atom trapped in the vicinity of a superconducting body. We
      derive a simple scaling law for the corresponding spin-flip lifetime for such an
      atom trapped near a superconducting thick slab. For temperatures below the
      superconducting transition temperature Tc, the lifetime is found to be enhanced
      by several orders of magnitude in comparison to the case of a normal conducting
      slab. At zero temperature the spin-flip lifetime is given by the unbounded free
      space value.

PMID- 17026214
TI  - Surface tension in unitary fermi gases with population imbalance.
AB  - We study the effects of surface tension between normal and superfluid regions of
      a trapped Fermi gas at unitarity. We find that surface tension causes notable
      distortions in the shape of large aspect ratio clouds. Including these
      distortions in our theories resolves many of the apparent discrepancies among
      different experiments and between theory and experiments.

PMID- 17026215
TI  - Controlled splitting of an atomic wave packet.
AB  - We propose a simple scheme capable of adiabatically splitting an atomic wave
      packet using two independent translating traps. Implemented with optical dipole
      traps, our scheme allows a high degree of flexibility for atom interferometry
      arrangements and highlights its potential as an efficient and high fidelity atom
      optical beam splitter.

PMID- 17026216
TI  - Released momentum distribution of a Fermi gas in the BCS-BEC crossover.
AB  - We develop a time-dependent mean-field theory to investigate the released
      momentum distribution and the released energy of an ultracold Fermi gas in the
      BCS-BEC crossover after the scattering length has been set to zero by a fast
      magnetic-field ramp. For a homogeneous gas we analyze the nonequilibrium dynamics
      of the system as a function of the interaction strength and of the ramp speed.
      For a trapped gas the theoretical predictions are compared with experimental
      results.

PMID- 17026217
TI  - AMANDA observations constrain the ultrahigh energy neutrino flux.
AB  - A number of experimental techniques are currently being deployed in an effort to
      make the first detection of ultrahigh energy cosmic neutrinos. To accomplish this
      goal, techniques using radio and acoustic detectors are being developed, which
      are optimally designed for studying neutrinos with energies in the PeV-EeV range
      and above. Data from the AMANDA experiment, in contrast, have been used to place
      limits on the cosmic neutrino flux at less extreme energies (up to approximately
      10 PeV). In this Letter, we show that by adopting a different analysis strategy,
      optimized for much higher energy neutrinos, the same AMANDA data can be used to
      place a limit competitive with radio techniques at EeV energies. We also discuss
      the sensitivity of the IceCube experiment, in various stages of deployment, to
      ultrahigh energy neutrinos.

PMID- 17026218
TI  - Stringent constraint on galactic positron production.
AB  - The intense 0.511 MeV gamma-ray line emission from the Galactic Center observed
      by INTEGRAL requires a large annihilation rate of nonrelativistic positrons. If
      these positrons are injected at even mildly relativistic energies, higher-energy
      gamma rays will also be produced. We calculate the gamma-ray spectrum due to
      inflight annihilation and compare it with the observed diffuse Galactic gamma-ray
      data. Even with a simplified but conservative treatment, we find that the
      positron injection energies must be less than or similar to 3 MeV, which strongly
      constrains models for Galactic positron production.

PMID- 17026219
TI  - Can sterile neutrinos be ruled out as warm dark matter candidates?
AB  - We present constraints on the mass of warm dark matter (WDM) particles from a
      combined analysis of the matter power spectrum inferred from the Sloan Digital
      Sky Survey Lyman-alpha flux power spectrum at 2.2<z<4.2, cosmic microwave
      background data, and the galaxy power spectrum. We obtain a lower limit of mWDM
      greater than or similar to 10 keV (2sigma) if the WDM consists of sterile
      neutrinos and mWDM greater than or similar to 2 keV (2sigma) for early decoupled
      thermal relics. If we combine this bound with the constraint derived from x-ray
      flux observations of the Coma cluster, we find that the allowed sterile neutrino
      mass is approximately 10 keV (in the standard production scenario). Adding
      constraints based on x-ray fluxes from the Andromeda galaxy, we find that dark
      matter particles cannot be sterile neutrinos, unless they are produced by a
      nonstandard mechanism (resonant oscillations, coupling with the inflation) or get
      diluted by a large entropy release.

PMID- 17026220
TI  - Two-loop anomalous-dimension matrix for soft-gluon exchange.
AB  - The resummation of soft-gluon exchange for QCD hard scattering requires a matrix
      of anomalous dimensions. We compute this matrix directly for arbitrary 2-->n
      massless processes for the first time at two loops. Using color-generator
      notation, we show that it is proportional to the one-loop matrix. This result
      reproduces all pole terms in dimensional regularization of the explicit
      calculations of massless 2-->2 amplitudes in the literature, and it predicts all
      poles at next-to-next-to-leading order in any 2-->n process that has been
      computed at next-to-leading order. The proportionality of the one- and two-loop
      matrices makes possible the resummation in closed form of the next-to-next-to
      leading logarithms and poles in dimensional regularization for the 2-->n
      processes.

PMID- 17026222
TI  - Yang-mills magnetofluid unification.
AB  - We generalize the hybrid magnetofluid model of a charged fluid interacting with
      an electromagnetic field to the dynamics of a relativistic hot fluid interacting
      with a non-Abelian field. The fluid itself is endowed with a non-Abelian charge
      and the consequences of this generalization are worked out. Applications of this
      formalism to the quark gluon plasma are suggested.

PMID- 17026223
TI  - Island of rare Earth nuclei with tetrahedral and octahedral symmetries: possible
      experimental evidence.
AB  - Calculations using realistic mean-field methods suggest the existence of nuclear
      shapes with tetrahedral Td and/or octahedral Oh symmetries sometimes at only a
      few hundreds of keV above the ground states in some rare earth nuclei around
      156Gd and 160Yb. The underlying single-particle spectra manifest exotic fourfold
      rather than Kramers's twofold degeneracies. The associated shell gaps are very
      strong, leading to a new form of shape coexistence in many rare earth nuclei. We
      present possible experimental evidence of the new symmetries based on the
      published experimental results--although an unambiguous confirmation will require
      dedicated experiments.

PMID- 17026224
TI  - High-resolution study of x-ray resonant Raman scattering at the K edge of
      silicon.
AB  - We report on the first high-resolution measurements of the K x-ray resonant Raman
      scattering (RRS) in Si. The measured x-ray RRS spectra, interpreted using the
      Kramers-Heisenberg approach, revealed spectral features corresponding to
      electronic excitations to the conduction and valence bands in silicon. The total
      cross sections for the x-ray RRS at the 1s absorption edge and the 1s-3p
      excitation were derived. The Kramers-Heisenberg formalism was found to reproduce
      quite well the x-ray RRS spectra, which is of prime importance for applications
      of the total-reflection x-ray fluorescence technique.

PMID- 17026225
TI  - Difference between a photon's momentum and an atom's recoil.
AB  - When an atom absorbs a photon from a laser beam that is not an infinite plane
      wave, the atom's recoil is less than variant Planck's k in the propagation
      direction. We show that the recoils in the transverse directions produce a
      lensing of the atomic wave functions, which leads to a frequency shift that is
      not discrete but varies linearly with the field amplitude and strongly depends on
      the atomic state detection. The same lensing effect is also important for
      microwave atomic clocks. The frequency shifts are of the order of the naive
      recoil shift for the transverse wave vector of the photons.

PMID- 17026226
TI  - Deterministic and nondestructively verifiable preparation of photon number
      states.
AB  - An experimentally viable approach for preparing arbitrary photon number states of
      a cavity mode using continuous measurement and real-time quantum feedback is
      presented. The procedure passively monitors the number state actually achieved in
      each feedback-stabilized measurement trajectory, thus providing nondestructively
      verifiable photon generation. The feasibility of a possible cavity QED
      implementation in the many-atom, good-cavity-coupling regime is analyzed.

PMID- 17026221
TI  - Measurement of deeply virtual compton scattering with a polarized-proton target.
AB  - The longitudinal target-spin asymmetry AUL for the exclusive electroproduction of
      high-energy photons was measured for the first time in ep-->e;'pgamma. The data
      have been accumulated at JLab with the CLAS spectrometer using 5.7 GeV electrons
      and a longitudinally polarized NH3 target. A significant azimuthal angular
      dependence was observed, resulting from the interference of the deeply virtual
      Compton scattering and Bethe-Heitler processes. The amplitude of the sinvarphi
      moment is 0.252+/-0.042stat+/-0.020sys. Theoretical calculations are in good
      agreement with the magnitude and the kinematic dependence of the target-spin
      asymmetry, which is sensitive to the generalized parton distributions H and H.

PMID- 17026227
TI  - All-angle broadband negative refraction of metal waveguide arrays in the visible
      range: theoretical analysis and numerical demonstration.
AB  - In this Letter, we introduce a simple metal waveguide array for realizing all
      angle wide frequency bandwidth negative refraction from the visible to infrared
      frequencies. Theoretical analysis from the rigorous coupled-wave theory reveals
      that the negative coupling constant resulting from the anomalous coupling of
      guided surface plasmon polariton modes contributes to the negative refraction.
      The analytical results are confirmed by finite-difference time-domain numerical
      simulations. Our result provides an alternative way to construct robust all-angle
      negative refractive materials operating in a wide range of frequency from the
      near-infrared to the visible range.

PMID- 17026228
TI  - Ambiguities in the scattering tomography for central potentials.
AB  - Invisibility devices exploit ambiguities in the inverse scattering problem of
      light in media. Scattering also serves as an important general tool to infer
      information about the structure of matter. We elucidate the nature of scattering
      ambiguities that arise in central potentials. We show that scattering is a
      tomographic projection: The integrated scattering angle is a projection of a
      scattering function onto the impact parameter. This function depends on the
      potential but may be multivalued, allowing for ambiguities where several
      potentials share the same scattering data. In addition, multivalued scattering
      angles also lead to ambiguities. We apply our theory to show that it is, in
      principle, possible to construct an invisibility device without infinite phase
      velocity of light.

PMID- 17026229
TI  - Controllable self-steepening of ultrashort pulses in quadratic nonlinear media.
AB  - By analyzing ultrashort optical pulse propagation in quadratic nonlinear media
      beyond the slowly varying envelope approximation, we find that the sign and
      magnitude of self-steepening can be controlled through the wave vector mismatch.
      As an example of this phenomenon's impact on ultrashort pulse propagation, we
      show that it may be used to cancel the propagation effects of group-velocity
      mismatch. We obtain quantitative agreement between theory, simulations, and
      experiments.

PMID- 17026230
TI  - Stable vortex tori in the three-dimensional cubic-quintic Ginzburg-Landau
      equation.
AB  - We demonstrate the existence of stable toroidal dissipative solitons with the
      inner phase field in the form of rotating spirals, corresponding to vorticity
      S=0, 1, and 2, in the complex Ginzburg-Landau equation with the cubic-quintic
      nonlinearity. The stable solitons easily self-trap from pulses with embedded
      vorticity. The stability is corroborated by accurate computation of growth rates
      for perturbation eigenmodes. The results provide the first example of stable
      vortex tori in a 3D dissipative medium, as well as the first example of higher
      order tori (with S=2) in any nonlinear medium. It is found that all stable
      vortical solitons coexist in a large domain of the parameter space; in smaller
      regions, there coexist stable solitons with either S=0 and S=1, or S=1 and S=2.

PMID- 17026231
TI  - Photonic crystal lens: from negative refraction and negative index to negative
      permittivity and permeability.
AB  - We consider a dielectric photonic crystal made of cylindrical holes in a high
      index matrix. We show that a given finite size photonic crystal can mimic a
      homogeneous material whose permittivity and permeability are negative. We pay
      attention to the limitation of the homogeneous medium model and the vital role of
      the truncation of the crystal.

PMID- 17026232
TI  - Spatial four wave mixing in nonlinear periodic structures.
AB  - We present the first experimental study of spatial four-wave mixing in photonic
      lattices, demonstrating universal aspects of nonlinear processes in periodic
      media, such as engineered phase matching, Bloch-wave folding, and continuous
      control over the band at which the interaction products emerge.

PMID- 17026233
TI  - Transport of magnetic field by a turbulent flow of liquid sodium.
AB  - We study the effect of a turbulent flow of liquid sodium generated in the von
      Karman geometry, on the localized field of a magnet placed close to the frontier
      of the flow. We observe that the field can be transported by the flow on
      distances larger than its integral length scale. In the most turbulent
      configurations, the mean value of the field advected at large distance vanishes.
      However, the rms value of the fluctuations increases linearly with the magnetic
      Reynolds number. The advected field is strongly intermittent.

PMID- 17026234
TI  - Bistability of a compliant cavity induced by acoustic radiation pressure.
AB  - We report on the first observation of multiple-order bistability due to acoustic
      radiation pressure in a compliant acoustic cavity formed between a spherical
      ultrasonic transducer immersed in water and the free liquid surface located at
      its focus. The hysteretic behavior of the cavity length, observed both with
      amplitude ramps and frequency sweeps, is accurately described using a one
      dimensional model of a compliant Fabry-Perot resonator assuming the acoustic
      radiation pressure to be the only coupling between the cavity and the acoustic
      field.

PMID- 17026235
TI  - Femtosecond undulator radiation from sliced electron bunches.
AB  - At the 1.7-GeV electron storage ring BESSY II, a first source of synchrotron
      radiation with 100 fs pulse duration, variable (linear and circular)
      polarization, tunable photon energy (300 to 1400 eV), and excellent signal-to
      background ratio was constructed and is now in routine operation.

PMID- 17026236
TI  - Laser seeding of the storage-ring microbunching instability for high-power
      coherent terahertz radiation.
AB  - We report the first observation of laser seeding of the storage-ring
      microbunching instability. Above a threshold bunch current, the interaction of
      the beam and its radiation results in a coherent instability, observed as a
      series of stochastic bursts of coherent synchrotron radiation (CSR) at terahertz
      frequencies initiated by fluctuations in the beam density. We have observed that
      this effect can be seeded by imprinting an initial density modulation on the beam
      by means of laser "slicing." In such a situation, most of the bursts of CSR
      become synchronous with the pulses of the modulating laser and their average
      intensity scales exponentially with the current per bunch. We present detailed
      experimental observations of the seeding effect and a model of the phenomenon.
      This seeding mechanism also creates potential applications as a high-power source
      of CSR at terahertz frequencies.

PMID- 17026237
TI  - Active-feedback control of the magnetic boundary for magnetohydrodynamic
      stabilization of a fusion plasma.
AB  - Stable operation with control on magnetohydrodynamic modes has been obtained in
      the modified reversed field experiment employing a set of 192 feedback controlled
      saddle coils. Improvements of plasma temperature, confinement (twofold), and
      pulse length (threefold) and, as a consequence of the magnetic fluctuation
      reduction, strong mitigation of plasma-wall interaction and mode locking are
      reported.

PMID- 17026238
TI  - Enhanced energy confinement and performance in a low-recycling tokamak.
AB  - Extensive lithium wall coatings and liquid lithium plasma-limiting surfaces
      reduce recycling, with dramatic improvements in Ohmic plasma discharges in the
      Current Drive Experiment-Upgrade. Global energy confinement times increase by up
      to 6 times. These results exceed confinement scalings such as ITER98P(y,1) by 2-3
      times, and represent the largest increase in energy confinement ever observed for
      an Ohmic tokamak plasma. Measurements of Dalpha emission indicate that global
      recycling coefficients decrease to approximately 0.3, the lowest documented for a
      magnetically confined hydrogen plasma.

PMID- 17026239
TI  - Upstream ionization instability associated with a current-free double layer.
AB  - A low frequency instability has been observed using various electrostatic probes
      in a low-pressure expanding helicon plasma. The instability is associated with
      the presence of a current-free double layer (DL). The frequency of the
      instability increases linearly with the potential drop of the DL, and
      simultaneous measurements show their coexistence. A theory for an upstream
      ionization instability has been developed, which shows that electrons accelerated
      through the DL increase the ionization upstream and are responsible for the
      observed instability. The theory is in good agreement with the experimental
      results.

PMID- 17026240
TI  - Effect of external static magnetic field on the emittance and total charge of
      electron beams generated by laser-Wakefield acceleration.
AB  - Significant enhancement of emittance and an increase of the total charge of
      femtosecond electron beams produced by a 12 TW, 40 fs laser pulse, tightly
      focused in a He gas jet, are observed after applying a static magnetic field, B>
      or =0.2 T, directed along the axis of laser pulse propagation. The effect appears
      when plasma produced by a laser prepulse becomes magnetized in the vicinity of
      the focus point: the electron Larmor frequency exceeds the collisional frequency,
      while periphery of the plasma remains unmagnetized. The entailed change in the
      shape of the plasma suppresses the diffraction of the main laser pulse that
      results in a much higher charge of electrons self-injected during the
      longitudinal wave breaking of the laser wake as well as the excellent stability
      of the beams.

PMID- 17026241
TI  - Critical Casimir force in 4He films: confirmation of finite-size scaling.
AB  - We present new capacitance measurements of critical Casimir force-induced
      thinning of 4He films near the superfluid transition, focused on the region below
      Tlambda where the effect is the greatest. 4He films of 238, 285, and 340 A
      thickness are adsorbed on atomically smooth, N-doped silicon substrates. The
      Casimir force scaling function theta, deduced from the thinning of these three
      films, collapses onto a single universal curve, attaining a minimum theta=-1.30+/
      0.03 at x=td1/nu=-9.7+/-0.8 A1/nu. The collapse confirms the finite-size scaling
      origin of the dip in the film thickness. Separately, we also confirm the presence
      down to 2.13 K of the Goldstone or surface fluctuation force, which makes the
      superfluid film approximately 2 A thinner than the normal film.

PMID- 17026242
TI  - Kink formation and motion in carbon nanotubes at high temperatures.
AB  - We report that kink motion is a universal plastic deformation mode in all carbon
      nanotubes when being tensile loaded at high temperatures. The kink motion,
      observed inside a high-resolution transmission electron microscope, is
      reminiscent of dislocation motion in crystalline materials: namely, it
      dissociates and multiplies. The kinks are nucleated from vacancy creation and
      aggregation, and propagate in either a longitudinal or a spiral path along the
      nanotube walls. The kink motion is related to dislocation glide and climb
      influenced by external stress and high temperatures in carbon nanotubes.

PMID- 17026243
TI  - Grain boundary transitions in binary alloys.
AB  - A thermodynamic diffuse interface analysis predicts that grain boundary
      transitions in solute absorption are coupled to localized structural order
      disorder transitions. An example calculation of a planar grain boundary using a
      symmetric binary alloy shows that first-order boundary transitions can be
      predicted as a function of the crystallographic grain boundary misorientation and
      empirical gradient coefficients. The predictions are compared to published
      experimental observations.

PMID- 17026244
TI  - Hydrogen-mediated nitrogen clustering in dilute III-V nitrides.
AB  - First-principles calculation reveals multi-N clusters to be the ground states for
      hydrogenated N in dilute III-V nitrides. While hydrogenation of a single N,
      forming H2*(N), can relax the large strain induced by the size-mismatched N,
      formation of the clusters will relax the strain even more effectively. This
      suppresses the formation of H2*(N), the existence of which has recently been
      debated. More importantly, postgrowth dehydrogenation of the N-H clusters
      provides an explanation to the observed metastable bare N clusters in GaAsN grown
      by gas-source molecular beam epitaxy or metal-organic chemical vapor deposition.

PMID- 17026245
TI  - Hall-petch law revisited in terms of collective dislocation dynamics.
AB  - The Hall-Petch (HP) law, that accounts for the effect of grain size on the
      plastic yield stress of polycrystals, is revisited in terms of the collective
      motion of interacting dislocations. Sudden relaxation of incompatibility stresses
      in a grain triggers aftershocks in the neighboring ones. The HP law results from
      a scaling argument based on the conservation of the elastic energy during such
      transfers. The Hall-Petch law breakdown for nanometric sized grains is shown to
      stem from the loss of such a collective behavior as grains start deforming by
      successive motion of individual dislocations.

PMID- 17026246
TI  - Dynamics and internal stress at the nanoscale related to unique thermomechanical
      behavior in polymer nanocomposites.
AB  - A small amount of alumina nanoparticles in polymethylmethacrylate causes a sharp
      depression of the glass transition temperature (Tg) accompanied by a toughening
      of the composite. We investigated this phenomenon using multispeckle x-ray photon
      correlation spectroscopy. Measurements reveal a dynamic structure factor that has
      the form exp[-(t/taua)beta], with beta greater than 1. We show for the first time
      that beta(T) tracks the internal stress at the polymer-particle interface. The
      internal stress, which we propose arises due to the entropic penalty that the
      polymer faces in the presence of the nanoparticles, engenders temporally
      heterogeneous dynamics. In the jammed glassy state, we show that the dominant
      fast relaxation mode--taumax--aided by a weak dewetting interface relieves the
      stress and follows the variations in Tg.

PMID- 17026247
TI  - Nonlinear analysis of oscillatory indentation in elastic and viscoelastic solids.
AB  - Determining the mechanical properties at micro- and nanometer length scales using
      nanoindentation or atomic force microscopy is important to many areas of science
      and engineering. Here we establish equations for obtaining storage and loss
      modulus from oscillatory indentations by performing a nonlinear analysis of
      conical and spherical indentation in elastic and viscoelastic solids. We show
      that, when the conical indenter is driven by a sinusoidal force, the square of
      displacement is a sinusoidal function of time, not the displacement itself, which
      is commonly assumed. Similar conclusions hold for spherical indentations. Well
      known difficulties associated with measuring contact area and correcting thermal
      drift may be circumvented using the newly derived equations. These results may
      help improve methods of using oscillatory indentation for determining elastic and
      viscoelastic properties of solids.

PMID- 17026248
TI  - Tuning of tetrahedrality in a silicon potential yields a series of monatomic
      (metal-like) glass formers of very high fragility.
AB  - We obtain monatomic glass formers in simulations by modifying the tetrahedral
      character in a silicon potential to explore a triple point zone between
      potentials favoring diamond (dc) and bcc crystals. dc crystallization is always
      preceded by a polyamorphic transformation of the liquid, and is frustrated when
      the Kauzmann temperature of the high temperature liquid intersects the liquid
      liquid coexistence line. The glass forming liquids are extraordinarily fragile.
      Our results suggest that Si and Ge liquids may be vitrified at a pressure close
      to the diamond-beta-tin-liquid triple point.

PMID- 17026249
TI  - Leakage of O2 precursor molecules from inert hydrogen islands on a Pt(111)
      surface.
AB  - We have observed, using infrared spectroscopy, that the precursor-mediated O2
      chemisorption on the clean and the partially hydrogen-covered Pt(111) surfaces
      exhibits opposite temperature dependencies above the temperature for stable O2
      physisorption. While the chemisorption probability on the clean surface increases
      with increasing temperature due to thermal activation of the precursor, it
      decreases on the partially hydrogen-covered surface which we suggest is due to a
      general loss of the mobile precursor molecules by thermal desorption from
      chemically inert hydrogen islands.

PMID- 17026250
TI  - In situ study of the growth of nanodots in organic heteroepitaxy.
AB  - We report the self-organization of organic nanodots with high crystallinity
      during the growth of organic heterostructures of Di-indenoperylene (DIP) onto
      copper-hexadecafluorophthalocyanine (F16CuPc), donor and acceptor molecules,
      respectively. The process is related to the Stranski-Krastanov growth mode, which
      is accompanied by a novel type of structural reconstruction of the underlying
      organic film. This reconstruction affects three monolayers adjacent to the
      organic interface. In spite of the close resemblance to the formation of
      semiconductor nanostructures for inorganic heteroepitaxy, the present results
      conclusively demonstrate a distinctly different growth mechanism for organic
      heteroepitaxy whose understanding demands further theoretical studies.

PMID- 17026251
TI  - High friction from a stiff polymer using microfiber arrays.
AB  - High dry friction requires intimate contact between two surfaces and is generally
      obtained using soft materials with an elastic modulus less than 10 MPa. We
      demonstrate that high-friction properties similar to rubberlike materials can
      also be obtained using microfiber arrays constructed from a stiff thermoplastic
      (polypropylene, 1 GPa). The fiber arrays have a smaller true area of contact than
      a rubberlike material, but polypropylene's higher interfacial shear strength
      provides an effective friction coefficient of greater than 5 at normal loads of 8
      kPa. At the pressures tested, the fiber arrays showed more than an order of
      magnitude increase in shear resistance compared to the bulk material. Unlike
      softer materials, vertical fiber arrays of stiff polymer demonstrate no
      measurable adhesion on smooth surfaces due to high tensile stiffness.

PMID- 17026252
TI  - Dissipation-driven quantum phase transitions in a Tomonaga-Luttinger liquid
      electrostatically coupled to a metallic gate.
AB  - The dissipation induced by a metallic gate on the low-energy properties of
      interacting 1D electron liquids is studied. As a function of the distance to the
      gate, or the electron density in the wire, the system can undergo a quantum phase
      transition from a Tomonaga-Luttinger liquid to two kinds of dissipative phases,
      one of them with a finite spatial correlation length. We also define a dual
      model, which describes an attractive one-dimensional metal with a Josephson
      coupling to a dirty metallic lead.

PMID- 17026253
TI  - Nonlinear magnetotransport in interacting chiral nanotubes.
AB  - Nonlinear transport through interacting single-wall nanotubes containing a few
      impurities is studied theoretically. Extending the Luttinger liquid theory to
      incorporate trigonal warping and chirality effects, we derive the current
      contribution Ie even in the applied voltage V and odd in an orbital magnetic
      field B, which is nonzero only for chiral tubes and in the presence of
      interactions.

PMID- 17026254
TI  - Optically probing spin and charge interactions in a tunable artificial molecule.
AB  - We optically probe and electrically control a single artificial molecule
      containing a well defined number of electrons. Charge and spin dependent interdot
      quantum couplings are probed optically by adding a single electron-hole pair and
      detecting the emission from negatively charged exciton states. Coulomb- and Pauli
      blockade effects are directly observed, and tunnel coupling and electrostatic
      charging energies are independently measured. The interdot quantum coupling is
      shown to be mediated by electron tunneling. Our results are in excellent accord
      with calculations that provide a complete picture of negative excitons and few
      electron states in quantum dot molecules.

PMID- 17026255
TI  - Finite-size error in many-body simulations with long-range interactions.
AB  - We discuss the origin of the finite-size error of the energy in many-body
      simulation of systems of charged particles and we propose a correction based on
      the random-phase approximation at long wavelengths. The correction is determined
      mainly by the collective charge oscillations of the interacting system. Finite
      size corrections, both on kinetic and potential energy, can be calculated within
      a single simulation. Results are presented for the electron gas and silicon.

PMID- 17026256
TI  - Continuous-time solver for quantum impurity models.
AB  - We present a new continuous-time solver for quantum impurity models such as those
      relevant to dynamical mean field theory. It is based on a stochastic sampling of
      a perturbation expansion in the impurity-bath hybridization parameter.
      Comparisons with Monte Carlo and exact diagonalization calculations confirm the
      accuracy of the new approach, which allows very efficient simulations even at low
      temperatures and for strong interactions. As examples of the power of the method
      we present results for the temperature dependence of the kinetic energy and the
      free energy, enabling an accurate location of the temperature-driven metal
      insulator transition.

PMID- 17026257
TI  - Spin cloud induced around an elastic scatterer by the intrinsic spin hall effect.
AB  - Similar to the Landauer electric dipole created around an impurity by the
      electric current, a spin polarized cloud of electrons can be induced by the
      intrinsic spin Hall effect near a spin independent elastic scatterer. It is shown
      that in the ballistic range around the impurity, such a cloud appears in the case
      of Rashba spin-orbit interaction, even though the bulk spin Hall current is
      absent.

PMID- 17026258
TI  - Direct measurement of the singlet generation yield in polymer light-emitting
      diodes.
AB  - In this study, the singlet and triplet exciton generation yields of a
      representative blue-emitting conjugated polymer are directly compared using
      simultaneous optical and electrical excitation measurements. After carefully
      accounting for bimolecular triplet annihilation and knowing the independently
      measured solid state inter-system-crossing yield of the polymer, a singlet
      generation yield of 44% is obtained, in the working device, which is clearly in
      excess of the simple quantum statistical 25% limit.

PMID- 17026259
TI  - Friedel sum rule for an interacting multiorbital quantum dot.
AB  - A generalized Friedel sum rule is derived for a quantum dot with internal orbital
      and spin degrees of freedom. The result is valid when all many-body correlations
      are taken into account and it links the phase shift of the scattered electron to
      the displacement of its spectral density into the dot.

PMID- 17026260
TI  - Fractional charge revealed in computer simulations of resonant tunneling in the
      fractional quantum Hall regime.
AB  - The concept of fractional charge is central to the theory of the fractional
      quantum Hall effect. Here I use exact diagonalization as well as configuration
      space renormalization to study finite clusters which are large enough to contain
      two independent edges. I analyze the conditions of resonant tunneling between the
      two edges. The "computer experiment" reveals a periodic sequence of resonant
      tunneling events consistent with the experimentally observed fractional
      quantization of electric charge in units of e/3 and e/5.

PMID- 17026261
TI  - Geometrical spin dephasing in quantum dots.
AB  - We study spin-orbit mediated relaxation and dephasing of electron spins in
      quantum dots. We show that higher order contributions provide a relaxation
      mechanism that dominates for low magnetic fields and is of geometrical origin. In
      the low-field limit relaxation is dominated by coupling to electron-hole
      excitations and possibly 1/f noise rather than phonons.

PMID- 17026262
TI  - Inelastic quantum transport and peierls-like mechanism in carbon nanotubes.
AB  - We report on a theoretical study of inelastic quantum transport in (3m,0) carbon
      nanotubes. By using a many-body description of the electron-phonon interaction in
      Fock space, a novel mechanism involving optical phonon emission (absorption) is
      shown to induce an unprecedented energy-gap opening at half the phonon energy,
      variant Planck's over 2piomega0/2, above (below) the charge neutrality point.
      This mechanism, which is prevented by Pauli blocking at low bias voltages, is
      activated at bias voltages on the order of variant Planck's over 2piomega0.

PMID- 17026263
TI  - Electrostatic force microscopy on oriented graphite surfaces: coexistence of
      insulating and conducting behaviors.
AB  - We present measurements of the electric potential fluctuations on the surface of
      highly oriented pyrolytic graphite using electrostatic force and atomic force
      microscopy. Micrometric domainlike potential distributions are observed even when
      the sample is grounded. Such potential distributions are unexpected given the
      good metallic conductivity of graphite because the surface should be an
      equipotential. Our results indicate the coexistence of regions with
      "metalliclike" and "insulatinglike" behaviors showing large potential
      fluctuations of the order of 0.25 V. In lower quality graphite, this effect is
      not observed. Experiments are performed in Ar and air atmospheres.

PMID- 17026264
TI  - Kondo effect of an adsorbed cobalt phthalocyanine (CoPc) molecule: the role of
      quantum interference.
AB  - It has been shown that by distorting a CoPc molecule adsorbed on a Au(111)
      surface a Kondo effect is induced with a temperature higher than 200 K. We
      examine a model in which an atom with strong Coulomb repulsion (Co) is surrounded
      by four atoms on a square (molecule lobes), with two atoms above and below it
      representing the apex of the STM tip and an atom on the gold surface (all with a
      single atomic orbital). The Hamiltonian is solved exactly for the isolated
      cluster, and, after connecting the leads, the conductance is calculated by
      standard techniques. Quantum interference prevents the existence of the Kondo
      effect when the orbitals on the square do not interact (undistorted molecule);
      the Kondo resonance shows up after switching on that interaction. The weight of
      the Kondo resonance is controlled by the interplay of couplings to the STM tip
      and the gold surface and between the molecule lobes.

PMID- 17026265
TI  - Quantum two-level systems in Josephson junctions as naturally formed qubits.
AB  - The two-level systems (TLSs) naturally occurring in Josephson junctions
      constitute a major obstacle for the operation of superconducting phase qubits.
      Since these TLSs can possess remarkably long decoherence times, we show that such
      TLSs can themselves be used as qubits, allowing for a well controlled
      initialization, universal sets of quantum gates, and readout. Thus, a single
      current-biased Josephson junction can be considered as a multiqubit register. It
      can be coupled to other junctions to allow the application of quantum gates to an
      arbitrary pair of qubits in the system. Our results indicate an alternative way
      to realize superconducting quantum information processing.

PMID- 17026266
TI  - Onset of dendritic flux avalanches in superconducting films.
AB  - We report a detailed comparison of experimental data and theoretical predictions
      for the dendritic flux instability, believed to be a generic behavior of type-II
      superconducting films. It is shown that a thermomagnetic model published very
      recently [Phys. Rev. B 73, 014512 (2006)10.1103/PhysRevB.73.014512] gives an
      excellent quantitative description of key features like the stability onset
      (first dendrite appearance) magnetic field, and how the onset field depends on
      both temperature and sample size. The measurements were made using magneto
      optical imaging on a series of different strip-shaped samples of MgB2. Excellent
      agreement is also obtained by reanalyzing data previously published for Nb.

PMID- 17026267
TI  - Scanning tunneling spectroscopy on the novel superconductor CaC6.
AB  - We present scanning tunneling microscopy and spectroscopy of the newly discovered
      superconductor CaC6. The tunneling conductance spectra, measured between 3 and 15
      K, show a clear superconducting gap in the quasiparticle density of states. The
      gap function extracted from the spectra is in good agreement with the
      conventional BCS theory with Delta0=1.6+/-0.2 meV. The possibility of gap
      anisotropy and two-gap superconductivity is also discussed. In a magnetic field,
      direct imaging of the vortices allows us to deduce a coherence length in the ab
      plane xiab approximately 33 nm.

PMID- 17026268
TI  - Coulomb blockade anisotropic magnetoresistance effect in a (Ga,Mn)As single
      electron transistor.
AB  - We observe low-field hysteretic magnetoresistance in a (Ga,Mn)As single-electron
      transistor which can exceed 3 orders of magnitude. The sign and size of the
      magnetoresistance signal are controlled by the gate voltage. Experimental data
      are interpreted in terms of electrochemical shifts associated with magnetization
      rotations. This Coulomb blockade anisotropic magnetoresistance is distinct from
      previously observed anisotropic magnetoresistance effects as it occurs when the
      anisotropy in a band structure derived parameter is comparable to an independent
      scale, the single-electron charging energy. Effective kinetic-exchange model
      calculations in (Ga,Mn)As show chemical potential anisotropies consistent with
      experiment and ab initio calculations in transition metal systems suggest that
      this generic effect persists to high temperatures in metal ferromagnets with
      strong spin-orbit coupling.

PMID- 17026269
TI  - First order phase transition in the frustrated triangular antiferromagnet
      CsNiCl3.
AB  - By means of high-resolution ultrasonic velocity measurements, as a function of
      temperature and magnetic field, the nature of the different low temperatures
      magnetic phase transitions observed for the quasi-one-dimensional compound
      CsNiCl3 is established. Special attention has been devoted to the field-induced
      120 degrees phase transition above the multicritical point in the H-T phase
      diagram where the elastic constant C44 reveals a steplike variation and
      hysteresis effects. These results represent the first experimental evidence that
      the 120 degrees phase transition is weakly first order and contradict the popular
      notion of new universality classes for chiral systems.

PMID- 17026270
TI  - In-plane anisotropy of the electronic structure for the charge- and orbital
      ordered state in half-doped manganite with layered structure.
AB  - We report on the in-plane anisotropy of the electronic response in the spin-,
      charge-, and orbital-ordered phase of a half-doped layered-structure manganite.
      The optical conductivity spectra for a single domain of Eu1/2Ca3/2MnO4
      unambiguously show the anisotropic charge dynamics which well corresponds to the
      theoretical calculation: the optical conductivity with the polarization along the
      zigzag ferromagnetic chain direction exhibits a smaller gap and a larger
      intensity at lower energies than that of the perpendicular polarization mostly
      due to the charge and orbital ordering and the associated quantum interference
      effect.

PMID- 17026271
TI  - Magnetic moment softening and domain wall resistance in Ni nanowires.
AB  - We perform ab initio calculations of the electronic structure and conductance of
      atomic-size Ni nanowires with domain walls only a few atomic lattice constants
      wide. We show that the hybridization between noncollinear spin states leads to a
      reduction of the magnetic moments in the domain wall resulting in the enhancement
      of the domain wall resistance. Experimental studies of the magnetic moment
      softening may be feasible with modern techniques such as scanning tunneling
      spectroscopy.

PMID- 17026272
TI  - Theoretical limit of the minimal magnetization switching field and the optimal
      field pulse for Stoner particles.
AB  - The theoretical limit of the minimal magnetization switching field and the
      optimal field pulse design for uniaxial Stoner particles are investigated. Two
      results are obtained. One is the existence of a theoretical limit of the smallest
      magnetic field out of all possible designs. It is shown that the limit is
      proportional to the damping constant in the weak damping regime and approaches
      the Stoner-Wohlfarth (SW) limit at large damping. For a realistic damping
      constant, this limit is more than 10 times smaller than that of so-called
      precessional magnetization reversal under a noncollinear static field. The other
      is on the optimal field pulse design: if the magnitude of a magnetic field does
      not change, but its direction can vary during a reversal process, there is an
      optimal design that gives the shortest switching time. The switching time depends
      on the field magnitude, damping constant, and magnetic anisotropy.

PMID- 17026273
TI  - Muon spin relaxation studies of superconductivity in a crystalline array of
      weakly coupled metal nanoparticles.
AB  - We report muon-spin-relaxation studies in weak transverse fields of the
      superconductivity in the metal cluster compound, Ga84[N(SiMe3)2]20
      Li6Br2(thf)20.2 toluene. The temperature and field dependence of the muon-spin
      relaxation rate and Knight shift clearly evidence type II bulk superconductivity
      below Tc approximately 7.8 K, with Bc1 approximately 0.06 T, Bc2 approximately
      0.26 T, kappa approximately 2, and weak flux pinning. The data are well described
      by the s-wave BCS model with weak electron-phonon coupling in the clean limit. A
      qualitative explanation for the conduction mechanism in this novel type of narrow
      band superconductor is presented.

PMID- 17026274
TI  - Unclustering transition in freely cooling wet granular matter.
AB  - The free cooling of one-dimensional wet granular matter is presented in the
      framework of the minimal capillary model. We demonstrate analytically and by
      extensive simulations that above a critical density, the clustering of wet
      granular matter is not monotonic in time, but undergoes a sharp unclustering
      transition. This precipitation of granular droplets out of the gas takes place
      when the granular temperature comes close to the energy scale set by the
      capillary interaction.

PMID- 17026275
TI  - Morphometric approach to the solvation free energy of complex molecules.
AB  - We show that the solvation free energy of a complex molecule such as a protein
      can be calculated using only four geometrical measures of the molecular structure
      and corresponding thermodynamical coefficients. We compare results from this
      morphometric approach to those obtained by an elaborate statistical-mechanical
      theory in liquid state physics for a large variety of different structures of
      protein G and find excellent agreement. Since the computational time is
      drastically reduced, the new approach provides a practical and efficient way for
      calculating the solvation free energy which can be employed when this quantity
      has to be calculated for a large number of structures, as in a simulation study
      of protein folding.

PMID- 17026276
TI  - Partial clustering in binary two-dimensional colloidal suspensions.
AB  - Strongly interacting binary mixtures of superparamagnetic colloidal particles
      confined to a two-dimensional water-air interface are examined by theory,
      computer simulation, and experiment. The mixture exhibits a partial clustering in
      equilibrium: in the voids of the matrix of unclustered big particles, the small
      particles form subclusters with a spongelike topology which is accompanied by a
      characteristic small-wave vector peak in the small-small structure factor. This
      partial clustering is a general phenomenon occurring for strongly coupled
      negatively nonadditive mixtures.

PMID- 17026277
TI  - "Universal" distribution of interearthquake times explained.
AB  - We propose a simple theory for the "universal" scaling law previously reported
      for the distributions of waiting times between earthquakes. It is based on a
      largely used benchmark model of seismicity, which just assumes no difference in
      the physics of foreshocks, mainshocks, and aftershocks. Our theoretical
      calculations provide good fits to the data and show that universality is only
      approximate. We conclude that the distributions of interevent times do not reveal
      more information than what is already known from the Gutenberg-Richter and the
      Omori power laws. Our results reinforce the view that triggering earthquakes by
      other earthquakes is a key physical mechanism to understand seismicity.

PMID- 17026278
TI  - Comment on "scaling behavior of the Portevin-Le Chatelier effect in an Al-2.5% Mg
      alloy".

PMID- 17026279
TI  - Comment on "self-similar chain of metal nanospheres as an efficient nanolens".

PMID- 17026281
TI  - Fate of vacancy-induced supersolidity in 4He.
AB  - The supersolid state of matter, exhibiting nondissipative flow in solids, has
      been elusive for 35 years. The recent discovery of a nonclassical moment of
      inertia in solid 4He by Kim and Chan provided the first experimental evidence,
      although the interpretation in terms of supersolidity of the ideal crystal phase
      remains a subject to debate. Using quantum Monte Carlo methods we investigate the
      long-standing question of vacancy-induced superflow and find that vacancies in a
      4He crystal phase separate instead of forming a supersolid. On the other hand,
      nonequilibrium vacancies relaxing on defects of polycrystalline samples could
      provide an explanation for the experimental observations.

PMID- 17026282
TI  - Environment-mediated control of a quantum system.
AB  - Recently, a new approach for the controllability of a two-dimensional quantum
      system S has been proposed, based on its interaction with an initially
      uncorrelated two-dimensional probe P whose initial state can be arbitrarily
      modified. Following this scheme and considering a particular model for the
      environment, we show that, in some specific cases, the environment-induced
      entanglement is rich enough to completely control the dynamics of S. Under
      suitable conditions on the interaction of S, P, and the environment, we prove
      that the state of S can be driven to an arbitrary target state by varying the
      initial state of P.

PMID- 17026283
TI  - Stable Skyrmions in spinor condensates.
AB  - Globally symmetric spinor condensates in free space are argued not to support
      stable topological defects in either two or three dimensions. In the latter case,
      however, we show that a topological Skyrmion can be stabilized by forcing it to
      adopt certain density profiles. A sufficient condition for the existence of
      Skyrmion solutions in three dimensions is formulated and illustrated in simple
      examples. Our results pertain to Bose-Einstein condensation in 87Rb.

PMID- 17026284
TI  - Degenerate Bose-Fermi mixture of metastable atoms.
AB  - We report the observation of simultaneous quantum degeneracy in a dilute gaseous
      Bose-Fermi mixture of metastable atoms. Sympathetic cooling of helium-3 (fermion)
      by helium-4 (boson), both in the lowest triplet state, allows us to produce
      ensembles containing more than 10(6) atoms of each isotope at temperatures below
      1 microK, and achieve a fermionic degeneracy parameter of T/TF = 0.45. Because of
      their high internal energy, the detection of individual metastable atoms with
      subnanosecond time resolution is possible, permitting the study of bosonic and
      fermionic quantum gases with unprecedented precision. This may lead to metastable
      helium becoming the mainstay of quantum atom optics.

PMID- 17026285
TI  - Optimal entanglement criterion for mixed quantum states.
AB  - We develop a strong and computationally simple entanglement criterion. The
      criterion is based on an elementary positive map Phi which operates on state
      spaces with even dimension N > or = 4. It is shown that Phi detects many
      entangled states with a positive partial transposition (PPT) and that it leads to
      a class of optimal entanglement witnesses. This implies that there are no other
      witnesses which can detect more entangled PPT states. The map Phi yields a
      systematic method for the explicit construction of high-dimensional manifolds of
      bound entangled states.

PMID- 17026286
TI  - Distinctive fluctuations in a confined geometry.
AB  - Spurred by recent theoretical predictions [Phys. Rev. E 69, 035102(R)
      (2004)10.1103/PhysRevE.69.035102; Surf. Sci. Lett. 598, L355
      (2005)10.1016/j.susc.2005.09.023], we find experimentally using STM line scans
      that the fluctuations of the step bounding a facet exhibit scaling properties
      distinct from those of isolated steps or steps on vicinal surfaces. The
      correlation functions go as t0.15 +/- 0.03 decidedly different from the t0.26 +/-
      0.02 behavior for fluctuations of isolated steps. From the exponents, we
      categorize the universality, confirming the prediction that the nonlinear term of
      the Kardar-Parisi-Zhang equation, long known to play a central role in
      nonequilibrium phenomena, can also arise from the curvature or potential
      asymmetry contribution to the step free energy.

PMID- 17026287
TI  - Scalar-field-dominated cosmology with a transient acceleration phase.
AB  - A new cosmological scenario driven by a slow rolling homogeneous scalar field
      whose exponential potential V(Phi) has a quadratic dependence on the field Phi in
      addition to the standard linear term is discussed. The derived equation of state
      for the field predicts a transient accelerating phase, in which the Universe was
      decelerated in the past, began to accelerate at redshift z approximately 1, is
      currently accelerated, but, finally, will return to a decelerating phase in the
      future. This overall dynamic behavior is profoundly different from the standard
      evolution of the cold dark matter model with a cosmological constant, and may
      alleviate some conflicts in reconciling the idea of a dark-energy-dominated
      universe with observables in String or M theory. Some theoretical predictions for
      the present scalar field plus dark matter dominated stage are confronted with
      cosmological observations in order to test the viability of the scenario.

PMID- 17026288
TI  - Simultaneous measurement of ionization and scintillation from nuclear recoils in
      liquid xenon for a dark matter experiment.
AB  - We report the first measurements of the absolute ionization yield of nuclear
      recoils in liquid xenon, as a function of energy and electric field. Independent
      experiments were carried out with two dual-phase time-projection chamber
      prototypes, developed for the XENON dark matter project. We find that the charge
      yield increases with decreasing recoil energy, and exhibits only a weak field
      dependence. These results are the first unambiguous demonstration of the
      capability of dual-phase xenon detectors to discriminate between electron and
      nuclear recoils down to 20 keV, a key requirement for a sensitive dark matter
      search.

PMID- 17026289
TI  - No-go theorem for k-essence dark energy.
AB  - We demonstrate that if k-essence can solve the coincidence problem and play the
      role of dark energy in the Universe, the fluctuations of the field have to
      propagate superluminally at some stage. We argue that this implies that
      successful k-essence models violate causality. It is not possible to define a
      time ordered succession of events in a Lorentz invariant way. Therefore, k
      essence cannot arise as a low energy effective field theory of a causal,
      consistent high energy theory.

PMID- 17026290
TI  - Measurement of the quark mixing parameter cos2phi1 using time-dependent Dalitz
      analysis of B0 -->D[KS(0)pi + pi-]h0.
AB  - We present a measurement of the angle phi1 of the Cabibbo-Kobayashi-Maskawa
      unitarity triangle using a time-dependent Dalitz analysis of D-->KS(0)pi + pi-
      decays produced in neutral B meson decay to a neutral D meson and a light meson
      (B0-->D*h0). The method allows a direct extraction of 2phi1 and, therefore, helps
      to resolve the ambiguity between 2phi1 and pi-2phi1 in the measurement of
      sin2phi1. We obtain sin2phi1= 0.78 +/- 0.44 +/- 0.22 and cos2varphi1 = 1.87(-0.53
      0.32)(+0.40 + 0.22). The sign of cos2phi1 is determined to be positive at 98.3%
      C.L.

PMID- 17026292
TI  - Threshold resummation in momentum space from effective field theory.
AB  - Methods from soft-collinear effective theory are used to perform the threshold
      resummation of Sudakov logarithms for the deep-inelastic structure function
      F2(x,Q2) in the end-point region x-->1 directly in momentum space. An explicit
      all-order formula is derived, which expresses the short-distance coefficient
      function C in the convolution F2 = C multiply sign in circle phi q in terms of
      Wilson coefficients and anomalous dimensions defined in the effective theory.
      Contributions associated with the physical scales Q2 and Q2(1-x) are separated
      from nonperturbative hadronic physics in a transparent way. A crucial ingredient
      to the momentum-space resummation is the exact solution to the integro
      differential evolution equation for the jet function, which is derived. The
      methods developed in this Letter can be applied to many other hard QCD processes.

PMID- 17026293
TI  - Unified picture for single transverse-spin asymmetries in hard-scattering
      processes.
AB  - Using lepton-pair production in hadron-hadron collisions as an example, we
      explore the relation between two well-known mechanisms for single-transverse-spin
      asymmetries in hard processes: twist-three quark-gluon correlations when the
      pair's transverse momentum is large, q perpendicular >> Lambda QCD, and time
      reversal-odd and transverse-momentum-dependent parton distributions when q
      perpendicular is much less than the pair's mass. We find that, although the two
      mechanisms each have their own domain of validity, they describe the same physics
      in the kinematic region where they overlap. This unifies the two mechanisms and
      imposes an important constraint on phenomenological studies.

PMID- 17026294
TI  - Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma
      reaction at E gamma = 1.5-2.4 GeV.
AB  - Differential cross sections and photon-beam asymmetries have been measured for
      the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using
      liquid deuterium and hydrogen targets with incident linearly polarized photon
      beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio
      of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin
      1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large
      positive asymmetries are observed, indicating the dominance of K* exchange. The
      large difference between the asymmetries for the K+ Sigma- and K+ Sigma0
      reactions cannot be explained by simple theoretical considerations based on Regge
      model calculations.

PMID- 17026296
TI  - Discovery of 109Xe and 105Te: superallowed alpha decay near doubly magic 100Sn.
AB  - Two new alpha emitters 109Xe and 105Te were identified through the observation of
      the 109Xe --> 105Te --> 101Sn alpha-decay chain. The 109Xe nuclei were produced
      in the fusion-evaporation reaction 54Fe(58Ni,3n)109Xe and studied using the
      Recoil Mass Spectrometer at the Holifield Radioactive Ion Beam Facility. Two
      transitions at Ealpha = 4062 +/- 7 keV and Ealpha = 3918 +/- 9 keV were
      interpreted as the l = 2 and l = 0 transitions from the 7/2+ ground state in
      109Xe (T1/2 = 13 +/- 2 ms) to the 5/2+ ground state and a 7/2+ excited state,
      located at 150 +/- 13 keV in 105Te. The observation of the subsequent decay of
      105Te marks the discovery of the lightest known alpha-decaying nucleus. The
      measured transition energy Ealpha = 4703 +/- 5 keV and half-life T1/2 = 620 +/-
      70 ns were used to determine the reduced alpha-decay width delta2. The ratio
      delta105Te(2)/delta213Po(2) of approximately 3 indicates a superallowed character
      of the alpha emission from 105Te.

PMID- 17026297
TI  - K isomers in 254No: probing single-particle energies and pairing strengths in the
      heaviest nuclei.
AB  - We have identified two isomers in 254No, built on two- and four-quasiparticle
      excitations, with quantum numbers K pi = 8- and (14+), as well as a low-energy 2
      quasiparticle Kpi = 3+ state. The occurrence of isomers establishes that K is a
      good quantum number and therefore that the nucleus has an axial prolate shape.
      The 2-quasiparticle states probe the energies of the proton levels that govern
      the stability of superheavy nuclei, test 2-quasiparticle energies from theory,
      and thereby check their predictions of magic gaps.

PMID- 17026298
TI  - In-plane theory of nonsequential triple ionization.
AB  - We describe first-principles in-plane calculations of nonsequential triple
      ionization of atoms in a linearly polarized intense laser pulse. In a fully
      classically correlated description, all three electrons respond dynamically to
      the nuclear attraction, the pairwise e-e repulsions, and the laser force
      throughout the duration of a 780 nm laser pulse. Nonsequential ejection is shown
      to occur in a multielectron, possibly multicycle and multidimensional,
      rescattering sequence that is coordinated by a number of sharp transverse
      recollimation impacts.

PMID- 17026299
TI  - Stark shift control of single optical centers in diamond.
AB  - Lifetime-limited optical excitation lines of single nitrogen-vacancy (NV) defect
      centers in diamond have been observed at liquid helium temperature. They display
      unprecedented spectral stability over many seconds and excitation cycles.
      Spectral tuning of the spin-selective optical resonances was performed via the
      application of an external electric field (i.e., the Stark shift). A rich variety
      of Stark shifts were observed including linear as well as quadratic components.
      The ability to tune the excitation lines of single NV centers has potential
      applications in quantum information processing.

PMID- 17026300
TI  - Dipole blockade at Forster resonances in high resolution laser excitation of
      Rydberg states of cesium atoms.
AB  - High resolution laser excitation of np Rydberg states of cesium atoms shows a
      dipole blockade at Forster resonances corresponding to the resonant dipole-dipole
      energy transfer of the np+np --> ns+(n+1)s reaction. The dipole-dipole
      interaction can be tuned on and off by the Stark effect, and such a process,
      observed for relatively low n(25-41), is promising for quantum gate devices. Both
      Penning ionization and saturation in the laser excitation can limit the range of
      observation of the dipole blockade.

PMID- 17026301
TI  - Controlling electronic spin relaxation of cold molecules with electric fields.
AB  - We present a theoretical study of atom-molecule collisions in superimposed
      electric and magnetic fields and show that dynamics of electronic spin relaxation
      in molecules at temperatures below 0.5 K can be manipulated by varying the
      strength and the relative orientation of the applied fields. The mechanism of
      electric field control of Zeeman transitions is based on an intricate interplay
      between intramolecular spin-rotation couplings and molecule-field interactions.
      We suggest that electric fields may affect chemical reactions through inducing
      nonadiabatic spin transitions and facilitate evaporative cooling of molecules in
      a magnetic trap.

PMID- 17026302
TI  - X-ray microprobe of orbital alignment in strong-field ionized atoms.
AB  - We have developed a synchrotron-based, time-resolved x-ray microprobe to
      investigate optical strong-field processes at intermediate intensities (10(14) -
      10(15) W/cm2). This quantum-state specific probe has enabled the direct
      observation of orbital alignment in the residual ion produced by strong-field
      ionization of krypton atoms via resonant, polarized x-ray absorption. We found
      strong alignment to persist for a period long compared to the spin-orbit coupling
      time scale (6.2 fs). The observed degree of alignment can be explained by models
      that incorporate spin-orbit coupling. The methodology is applicable to a wide
      range of problems.

PMID- 17026303
TI  - Cooling to the ground state of axial motion for one atom strongly coupled to an
      optical cavity.
AB  - Localization to the ground state of axial motion is demonstrated for a single,
      trapped atom strongly coupled to the field of a high finesse optical resonator.
      The axial atomic motion is cooled by way of coherent Raman transitions on the red
      vibrational sideband. An efficient state detection scheme enabled by strong
      coupling in cavity QED is used to record the Raman spectrum, from which the state
      of atomic motion is inferred. We find that the lowest vibrational level of the
      axial potential with zero-point energy variant Planck's over 2 h omega a/2kB = 13
      microK is occupied with probability P0 approximately 0.95.

PMID- 17026304
TI  - Light diffraction by a strong standing electromagnetic wave.
AB  - The nonlinear quantum interaction of a linearly polarized x-ray probe beam with a
      focused intense standing laser wave is studied theoretically. Because of the
      tight focusing of the standing laser pulse, diffraction effects arise for the
      probe beam as opposed to the corresponding plane wave scenario. A quantitative
      estimate for realistic experimental conditions of the ellipticity and the
      rotation of the main polarization plane acquired by the x-ray probe after the
      interaction shows that the implementation of such vacuum effects is feasible with
      future X-ray Free Electron Laser light.

PMID- 17026305
TI  - Generation of a superposition of odd photon number states for quantum information
      networks.
AB  - We report on the experimental observation of quantum-network-compatible light
      described by a nonpositive Wigner function. The state is generated by photon
      subtraction from a squeezed vacuum state produced by a continuous wave optical
      parametric amplifier. Ideally, the state is a coherent superposition of odd
      photon number states, closely resembling a superposition of weak coherent states
      |alpha > - |-alpha >. In the limit of low squeezing the state is basically a
      single photon state. Light is generated with about 10,000 and more events per
      second in a nearly perfect spatial mode with a Fourier-limited frequency
      bandwidth which matches well atomic quantum memory requirements. The generated
      state of light is an excellent input state for testing quantum memories, quantum
      repeaters, and linear optics quantum computers.

PMID- 17026291
TI  - Search for a neutral Higgs boson decaying to a W boson pair in pp collisions at
      square root of s = 1.96 TeV.
AB  - We present the results of a search for standard model Higgs boson production with
      decay to WW*, identified through the leptonic final states e+ e- nu nu,+/-mu 
      /+nu nu and mu+ mu- nu nu. This search uses 360 pb -1 of data collected from pp
      collisions at square root of s =1.96 TeV by the upgraded Collider Detector at
      Fermilab (CDF II). We observe no signal excess and set 95% confidence level upper
      limits on the production cross section times branching ratio for the Higgs boson
      to WW* or any new scalar particle with similar decay products. These upper limits
      range from 5.5 to 3.2 pb for Higgs boson masses between 120 and 200 GeV/c2.

PMID- 17026306
TI  - Observation of surface gap solitons in semi-infinite waveguide arrays.
AB  - We report on the observation of surface gap solitons found to exist at the
      interface between uniform and periodic dielectric media with defocusing
      nonlinearity. We demonstrate strong self-trapping at the edge of a LiNbO3
      waveguide array and the formation of staggered surface solitons with propagation
      constant inside the first photonic band gap. We study the crossover between
      linear repulsion and nonlinear attraction at the surface, revealing the mechanism
      of nonlinearity-mediated stabilization of the surface gap modes.

PMID- 17026307
TI  - Model system for a one-dimensional magnetic photonic crystal.
AB  - We fabricate and characterize one-dimensional magnetic (rather than dielectric)
      photonic crystals for the first time. Our model system is a one-dimensional
      periodic lattice of gold-wire pairs. Each pair can be viewed as a magnetic coil
      with two slits and represents a "magnetic atom." Strong coupling between the
      resulting magnetic-dipole resonance and the Bragg resonance is accomplished by an
      adjacent dielectric slab waveguide, giving rise to an avoided crossing at near
      infrared wavelengths. Our experimental findings are in excellent agreement with
      theory.

PMID- 17026308
TI  - Experimental detection of the optical Pendellosung effect.
AB  - We report observations of periodic oscillatory behavior of the angular
      selectivity, near the Bragg angle, in volume holographic gratings recorded in a
      new photopolymerizable glass with high refractive index modulation. We have
      detected the presence of overmodulation in the intensity distribution of the
      first diffraction order. The results reported here were achieved by incorporating
      in the photopolymerizable sol-gel glass zirconium-based high refractive index
      species at the molecular level. This is the first time that this effect is
      observed for light diffraction in an amorphous material.

PMID- 17026309
TI  - Single-shot spectrometry for x-ray free-electron lasers.
AB  - An experimental scheme to realize single-shot spectrometry for the diagnostics of
      x-ray free-electron lasers (XFELs) is presented. The combination of an
      ultraprecisely figured mirror and a perfect crystal form a simple, high-precision
      spectrometer that can cover an energy range from a few eV to a hundred eV with
      high resolution. The application of the spectrometer to determine XFEL pulse
      widths was investigated theoretically and experimentally. It has been shown that
      the present system can determine pulse widths from sub-fs to ps in a single shot
      even for spontaneous radiation. The system can be easily extended to even shorter
      pulses.

PMID- 17026310
TI  - Relativistic AC gyromagnetic effects in ultraintense laser-matter interaction.
AB  - We demonstrate that in ultraintense ultrafast laser-matter interaction, the
      interplay of laser-induced oscillating space-charge fields with laser E and B
      fields can strongly affect whether the interaction is relativistic or not:
      stronger laser fields may not in fact produce more relativistic plasma
      interactions. We show that there exists a regime of interaction, in the relation
      of laser intensity and incident angle, for which the Brunel effect of electron
      acceleration is strongly suppressed by AC gyromagnetic fields, at a frequency
      different from the laser field. Analytically and with 1.5D particle-in-cell
      modeling, we show that from gyromagnetic effects, even in the absence of usual J
      x B second-harmonic contributions, there are strong effects on the harmonic
      emission and on the generation of attosecond pulses.

PMID- 17026311
TI  - Zonal flows in tokamak plasmas with toroidal rotation.
AB  - Zonal flows in tokamak plasmas with toroidal rotation are theoretically
      investigated. It is found that the low-frequency branch of zonal flows, which is
      linearly stable in a nonrotating system, becomes linearly unstable in a rotating
      tokamak, and that the high-frequency branch of zonal flows, the geodesic acoustic
      mode, can propagate in the poloidal direction with the frequency significantly
      lower than the frequency of the standing wave geodesic acoustic mode in the
      nonrotating system.

PMID- 17026312
TI  - Forced magnetic reconnection and field penetration of an externally applied
      rotating helical magnetic field in the TEXTOR tokamak.
AB  - The magnetic field penetration process into a magnetized plasma is of basic
      interest both for plasma physics and astrophysics. In this context special
      measurements on the field penetration and field amplification are performed by a
      Hall probe on the dynamic ergodic divertor (DED) on the TEXTOR tokamak and the
      data are interpreted by a two-fluid plasma model. It is observed that the growth
      of the forced magnetic reconnection by the rotating DED field is accompanied by a
      change of the plasma fluid rotation. The differential rotation frequency between
      the DED field and the plasma plays an important role in the process of the
      excitation of tearing modes. The momentum input from the rotating DED field to
      the plasma is interpreted by both a ponderomotive force at the rational surface
      and a radial electric field modified by an edge ergodization.

PMID- 17026295
TI  - Measurement of the tt production cross section in pp collisions at square root of
      s = 1.96 TeV.
AB  - We present a measurement of the top quark pair production cross section in pp
      collisions at square root of s = 1.96 TeV using 318 pb(-1) of data collected with
      the Collider Detector at Fermilab. We select tt[over ] decays into the final
      states enu+jets and mu nu+ jets, in which at least one b quark from the t-quark
      decays is identified using a secondary vertex-finding algorithm. Assuming a top
      quark mass of 178 GeV/c2, we measure a cross section of 8.7 +/- 0.9(stat)(
      0.9)+1.1(syst) pb. We also report the first observation of tt[over ] with
      significance greater than 5sigma in the subsample in which both b quarks are
      identified, corresponding to a cross section of 10.1(-1.4)+1.6(stat)(
      1.3)+2.0(syst) pb.

PMID- 17026313
TI  - Anomalous ion channeling in AlInN/GaN bilayers: determination of the strain
      state.
AB  - Monte Carlo simulations of anomalous ion channeling in near-lattice-matched
      AlInN/GaN bilayers allow an accurate determination of the strain state of AlInN
      by Rutherford backscattering or channeling. Although these strain estimates agree
      well with x-ray diffraction (XRD) results, XRD composition estimates are shown to
      have limited accuracy, due to a possible deviation from Vegard's law, which we
      quantify for this alloy. As the InN fraction increases from 13% to 19%, the
      strain in AlInN films changes from tensile to compressive with lattice matching
      predicted to occur at [InN] = 17.1%.

PMID- 17026314
TI  - Low frequency Raman scattering from acoustic phonons confined in ZnO
      nanoparticles.
AB  - We report here the first observation of the low frequency Raman scattering from
      acoustic phonons in semiconducting zinc oxide (ZnO) nanoparticles without
      embedding in any solid matrix. ZnO nanoparticles (size 5-10 nm) with nearly
      spherical shape have been synthesized using a chemical route. A shift in the
      phonon peaks toward higher frequencies along with broadening was observed with a
      decrease in particle size. The size dependence of the acoustic phonons in ZnO
      nanoparticles is explained using Lamb's theory that predicts the vibrational
      frequencies of a homogeneous elastic body of spherical shape. Our results show
      that the observed low frequency Raman scattering originates from the spherical (l
      = 0) and quadrupolar vibrations (l = 2) of the spheroidal mode due to the
      confinement of acoustic vibrations in ZnO nanoparticles.

PMID- 17026316
TI  - Isotope effect on the thermal conductivity of boron nitride nanotubes.
AB  - We have measured the temperature-dependent thermal conductivity kappa(T) of
      individual multiwall boron nitride nanotubes using a microfabricated test fixture
      that allows direct transmission electron microscopy characterization of the tube
      being measured. kappa(T) is exceptionally sensitive to isotopic substitution,
      with a 50% enhancement in kappa(T) resulting for boron nitride nanotubes with
      99.5% 11B. For isotopically pure boron nitride nanotubes, kappa rivals that of
      carbon nanotubes of similar diameter.

PMID- 17026315
TI  - O8 cluster structure of the epsilon phase of solid oxygen.
AB  - Despite many experimental and theoretical studies, the crystal structure of the
      epsilon phase of solid oxygen has not been determined. We performed powder x-ray
      diffraction experiments and the Rietveld analyses in this study to show that a
      new arrangement of the monoclinic space group C2/m could fit the diffraction
      patterns of the epsilon phase and obtained a structure that consisted of an O8
      cluster with 4 molecules. The dependence of the lattice parameters, the molar
      volume, and the intermolecular distances on the pressure was investigated.

PMID- 17026317
TI  - What controls deposition rate in electron-beam chemical vapor deposition?
AB  - The key physical processes governing electron-beam-assisted chemical vapor
      deposition are analyzed via a combination of theoretical modeling and supporting
      experiments. The scaling laws that define growth of the nanoscale deposits are
      developed and verified using carefully designed experiments of carbon deposition
      from methane onto a silicon substrate. The results suggest that the chamber-scale
      continuous transport of the precursor gas is the rate controlling process in
      electron-beam chemical vapor deposition.

PMID- 17026318
TI  - Superhard nitride-based nanocomposites: role of interfaces and effect of
      impurities.
AB  - Recently, a hardness similar to that of diamond has been reported for a
      quasiternary, nitride-based nanocomposite. The related, quasibinary nanocomposite
      "nc-TiN/a-Si3N4," which may be regarded as the prototype of the family of
      superhard nc-metal-N/a-Si3N4 systems, also exhibits a significant hardness
      enhancement. Extensive density-functional theory calculations indicate that the
      superhardness is related to the preferential formation of TiN(111) polar
      interfaces with a thin beta-Si3N4-derived layer. The strength of TiN in the 111
      direction is similar to that of the weakest bonding direction in diamond. Oxygen
      impurities cause a significant reduction of the interface strength.

PMID- 17026319
TI  - Multiregional hybrid method and its application: formation of an atomic
      protrusion at an atomic force microscope tip apex.
AB  - We present a multiregional hybrid scheme which incorporates first-principles
      (FP), tight-binding (TB), and molecular mechanical calculations. The key to this
      hybrid scheme is to find an explicit description of the FP-TB region coupling. We
      apply it to the atomic structure of a clean silicon atomic force microscope tip,
      and find the formation of a distinct atomic protrusion at the tip apex. The
      present study gives the reason why the atomic protrusion exits at the apex
      despite the fact that the atomic geometry of the very end of the tip is
      practically uncontrollable in the tip preparation.

PMID- 17026320
TI  - Magnetically mediated transparent conductors: In2O3 doped with Mo.
AB  - First-principles band structure investigations of the electronic, optical, and
      magnetic properties of Mo-doped In2O3 reveal the vital role of magnetic
      interactions in determining both the electrical conductivity and the Burstein
      Moss shift which governs optical absorption. We demonstrate the advantages of the
      transition metal doping which results in smaller effective mass, larger
      fundamental band gap, and better overall optical transmission in the visible as
      compared to commercial Sn-doped In2O3. Similar behavior is expected upon doping
      with other transition metals opening up an avenue for the family of efficient
      transparent conductors mediated by magnetic interactions.

PMID- 17026321
TI  - Fractional shot noise in the kondo regime.
AB  - Transport through quantum dots in the Kondo regime obeys an effective low
      temperature theory in terms of weakly interacting quasiparticles. Despite the
      weakness of the interaction, we find that the backscattering current and hence
      the shot noise are dominated by two-quasiparticle scattering. We show that the
      simultaneous presence of one- and two-quasiparticle scattering results in a
      universal average charge 5/3e as measured by shot-noise experiments. An
      experimental verification of our prediction would constitute a most stringent
      test of the low-energy theory of the Kondo effect.

PMID- 17026322
TI  - Spin-dependent quasiparticle transport in aluminum single-electron transistors.
AB  - We investigate the effect of Zeeman splitting on quasiparticle transport in
      normal-superconducting-normal (NSN) aluminum single-electron transistors (SETs).
      In the above-gap transport, the interplay of Coulomb blockade and Zeeman
      splitting leads to spin-dependence of the sequential tunneling. This creates
      regimes where either one or both spin species can tunnel onto or off the island.
      At lower biases, spin-dependence of the single quasiparticle state is studied,
      and operation of the device as a bipolar spin filter is suggested.

PMID- 17026323
TI  - Extreme ultrafast dynamics of quasiparticles excited in surface electronic bands.
AB  - We develop a many-body description of the nonadiabatic dynamics of quasiparticles
      in surface bands valid on an extremely ultrashort time scale by combining the
      formalism for the calculation of quasiparticle survival probabilities with the
      self-consistent treatment of the electronic response of the system. Applying this
      approach to the benchmark Cu(111) surface, we assess the behavior and intervals
      of preasymptotic electron and hole dynamics in surface bands and locate the
      transition to the asymptotic regime of the exponential quasiparticle decay
      characterized by the corrected Fermi golden rule-type of transition rate. The
      general validity of these findings enables distinguishing the various regimes of
      ultrafast electron dynamics that may be revealed in time resolved experiments.

PMID- 17026324
TI  - Crossed Andreev reflection-induced magnetoresistance.
AB  - We show that very large negative magnetoresistance can be obtained in magnetic
      trilayers in a current-in-plane geometry owing to the existence of crossed
      Andreev reflection. This spin valve consists of a thin superconducting film
      sandwiched between two ferromagnetic layers whose magnetization is allowed to be
      either parallelly or antiparallelly aligned. For a suitable choice of structure
      parameters and nearly fully spin-polarized ferromagnets, the magnetoresistance
      can exceed -80%. Our results are relevant for the design and implementation of
      spintronic devices exploiting ferromagnet-superconductor structures.

PMID- 17026325
TI  - First-principles periodic calculation of four-body spin terms in high-Tc cuprate
      superconductors.
AB  - A general mapping between the energy of pertinent magnetic solutions and the
      diagonal terms of the spin Hamiltonian in a local representation provides the
      first general framework to extract accurate values for the many body terms of
      extended spin Hamiltonians from periodic first-principle calculations. Estimates
      of these terms for La2CuO4, the paradigm of high-Tc superconductor parent
      compounds, and for the SrCu2O3 ladder compound are reported. For La2CuO4, present
      results support experimental evidence by Toader et al. [Phys. Rev. Lett. 94,
      197202 (2005)10.1103/PhysRevLett.94.197202]. For SrCu2O3 even larger four-body
      spin amplitudes are found together with Jl/Jr = 1 and non-negligible
      ferromagnetic interladder exchange.

PMID- 17026326
TI  - Highly spin-polarized field emissions induced by quantum size effects in
      ultrathin films of Fe on W(001).
AB  - Spin-polarized field emissions from Fe pseudomorphic ultrathin films on W(001)
      surfaces are studied by density functional calculations. We found that nearly
      completely spin-polarized field emission currents can be realized in two and four
      Fe layers on W(001) and that these systems have the additional advantages of
      thermal stability and low work functions. The unusually high spin polarizations
      of the field emission current is traced to the Fe film's quantum size effects
      leading to spin-polarized quantum well states and surface resonance states.

PMID- 17026327
TI  - Absence of magnetism in hcp iron-nickel at 11 K.
AB  - Synchrotron Mossbauer spectroscopy (SMS) was performed on an hcp-phase alloy of
      composition Fe92Ni8 at a pressure of 21 GPa and a temperature of 11 K. Density
      functional theoretical calculations predict antiferromagnetism in both hcp Fe and
      hcp Fe-Ni. For hcp Fe, these calculations predict no hyperfine magnetic field,
      consistent with previous experiments. For hcp Fe-Ni, however, substantial
      hyperfine magnetic fields are predicted, but these were not observed in the SMS
      spectra. Two possible explanations are suggested. First, small but significant
      errors in the generalized gradient approximation density functional may lead to
      an erroneous prediction of magnetic order or of erroneous hyperfine magnetic
      fields in antiferromagnetic hcp Fe-Ni. Alternately, quantum fluctuations with
      periods much shorter than the lifetime of the nuclear excited state would
      prohibit the detection of moments by SMS.

PMID- 17026328
TI  - Ultrahigh frequency nanotube resonators.
AB  - We report carbon-nanotube-based electromechanical resonators with the fundamental
      mode frequency over 1.3 GHz, operated in air at room temperature. A new
      combination of drive and detection methods allows for unprecedented measurement
      of both oscillation amplitude and phase and elucidates the relative mobility of
      static charges near the nanotube. The resonator serves as an exceptionally
      sensitive mass detector capable of approximately 10(-18) g resolution.

PMID- 17026329
TI  - Spin-driven phonon splitting in bond-frustrated ZnCr2S4.
AB  - Magnetic susceptibility, specific heat, thermal expansion, and IR spectroscopy
      provide experimental evidence that the two subsequent antiferromagnetic
      transitions in ZnCr2S4 at TN1 = 15 K and TN2 = 8 K are accompanied by significant
      thermal and phonon anomalies. The anomaly at TN2 reveals a temperature hysteresis
      typical for a first-order transformation. Because of strong spin-phonon coupling,
      both magnetic transitions at TN1 and TN2 induce a splitting of phonon modes. The
      anomalies and phonon splitting observed at TN2 are suppressed by strong magnetic
      field. Regarding the small positive Curie-Weiss temperature Theta approximately 8
      K, we argue that this scenario of two different magnetic phases with different
      magnetoelastic couplings results from the strong competition of ferromagnetic and
      antiferromagnetic exchange.

PMID- 17026330
TI  - Quadrupolar phases of the s=1 bilinear-biquadratic Heisenberg model on the
      triangular lattice.
AB  - Using mean-field theory, exact diagonalizations, and SU(3) flavor theory, we have
      precisely mapped out the phase diagram of the S = 1 bilinear-biquadratic
      Heisenberg model on the triangular lattice in a magnetic field, with emphasis on
      the quadrupolar phases and their excitations. In particular, we show that
      ferroquadrupolar order can coexist with short-range helical magnetic order, and
      that the antiferroquadrupolar phase is characterized by a remarkable 2/3
      magnetization plateau, in which one site per triangle retains quadrupolar order
      while the other two are polarized along the field. Implications for actual S=1
      magnets are discussed.

PMID- 17026331
TI  - Electrical measurement of spin-wave interactions of proximate spin transfer
      nanooscillators.
AB  - We have investigated the interaction mechanism between two nanocontact spin
      transfer oscillators made on the same magnetic spin valve multilayer. The
      oscillators phase lock when their precession frequencies are made similar, and a
      giant magnetoresistance signal is detectable at one contact due to precession at
      the other. Cutting the magnetic mesa between the contacts with a focused-ion beam
      modifies the contact outputs, eliminates the phase locking, and strongly
      attenuates the magnetoresistance coupling, which indicates that spin waves rather
      than magnetic fields are the primary interaction mechanism.

PMID- 17026332
TI  - Zeeman effect in superconducting two-leg ladders: irrational magnetization
      plateaus and exceeding the Pauli limit.
AB  - The effect of a parallel magnetic field on superconducting two-leg ladders is
      investigated numerically. The magnetization curve displays an irrational plateau
      at a magnetization equal to the hole density. Remarkably, its stability is
      fundamentally connected to the existence of a well-known magnetic resonant mode.
      Once the zero-field spin gap is suppressed by the field, pairs acquire a finite
      momentum characteristic of a Fulde-Ferrell-Larkin-Ovchinnikov phase. In addition,
      Sz = 0 triplet superconducting correlations coexist with singlet ones above the
      irrational plateau. This provides a simple mechanism in which the Pauli limit is
      exceeded as suggested by recent experiments.

PMID- 17026333
TI  - Impurity band conduction in a high temperature ferromagnetic semiconductor.
AB  - The band structure of a prototypical dilute magnetic semiconductor (DMS), Ga1
      xMnxAs, is studied across the phase diagram via infrared and optical
      spectroscopy. We prove that the Fermi energy (EF) resides in a Mn-induced
      impurity band (IB). Specifically the changes in the frequency dependent optical
      conductivity [sigma1(omega)] with carrier density are only consistent with EF
      lying in an IB. Furthermore, the large effective mass (m*) of the carriers
      inferred from our analysis of sigma1(omega) supports this conclusion. Our
      findings demonstrate that the metal to insulator transition in this DMS is
      qualitatively different from other III-V semiconductors doped with nonmagnetic
      impurities. We also provide insights into the anomalous transport properties of
      Ga1-xMnxAs.

PMID- 17026334
TI  - Supersolid phases in the one-dimensional extended soft-core bosonic Hubbard
      model.
AB  - We present results of quantum Monte Carlo simulations for the soft-core extended
      bosonic Hubbard model in one dimension exhibiting the presence of supersolid
      phases similar to those recently found in two dimensions. We find that in one and
      two dimensions, the insulator-supersolid transition has dynamic critical exponent
      z = 2 whereas the first order insulator-superfluid transition in two dimensions
      is replaced by a continuous transition with z = 1 in one dimension. We present
      evidence that this transition is in the Kosterlitz-Thouless universality class
      and discuss the mechanism behind this difference. The simultaneous presence of
      two types of quasi-long-range order results in two solitonlike dips in the
      excitation spectrum.

PMID- 17026335
TI  - First-principles theory of quantum well resonance in double barrier magnetic
      tunnel junctions.
AB  - Quantum well (QW) resonances in Fe(001)/MgO/Fe/MgO/Fe double barrier magnetic
      tunnel junctions are calculated from first principles. By including the Coulomb
      blockade energy due to the finite size islands of the middle Fe film, we confirm
      that the oscillatory differential resistance observed in a recent experiment [T.
      Nozaki, Phys. Rev. Lett. 96, 027208 (2006)10.1103/PhysRevLett.96.027208]
      originates from the QW resonances from the Delta1 band of the Fe majority-spin
      channel. The primary source of smearing at low temperatures is shown to be the
      variation of the Coulomb blockade energy.

PMID- 17026336
TI  - Polarization and readout of coupled single spins in diamond.
AB  - We study the coupling of a single nitrogen-vacancy center in diamond to a nearby
      single nitrogen defect at room temperature. The magnetic dipolar coupling leads
      to a splitting in the electron spin resonance frequency of the nitrogen-vacancy
      center, allowing readout of the state of a single nitrogen electron spin. At
      magnetic fields where the spin splitting of the two centers is the same, we
      observe a strong polarization of the nitrogen electron spin. The amount of
      polarization can be controlled by the optical excitation power. We combine the
      polarization and the readout in time-resolved pump-probe measurements to
      determine the spin relaxation time of a single nitrogen electron spin. Finally,
      we discuss indications for hyperfine-induced polarization of the nitrogen nuclear
      spin.

PMID- 17026337
TI  - Isotropic-nematic interface and wetting in suspensions of colloidal platelets.
AB  - We study interfacial phenomena in a colloidal dispersion of sterically stabilized
      gibbsite platelets, exhibiting coexisting isotropic and nematic phases separated
      by a sharp horizontal interface. The nematic phase wets a vertical glass wall and
      polarized light micrographs reveal homeotropic surface anchoring both at the free
      isotropic-nematic interface and at the wall. On the basis of complete wetting of
      the wall by the nematic phase, as found in our density functional calculations
      and computer simulations, we analyze the balance between Frank elasticity and
      surface anchoring near the contact line. Because of weak surface anchoring, the
      director field in the capillary rise region is uniform. From the measured rise (6
      microm) of the meniscus at the wall we determine the isotropic-nematic surface
      tension to be 3 nN/m, in quantitative agreement with our theoretical and
      simulation results.

PMID- 17026338
TI  - Nanobubbles in solid-state nanopores.
AB  - From conductance and noise studies, we infer that nanometer-sized gaseous bubbles
      (nanobubbles) are the dominant noise source in solid-state nanopores. We study
      the ionic conductance through solid-state nanopores as they are moved through the
      focus of an infrared laser beam. The resulting conductance profiles show strong
      variations in both the magnitude of the conductance and in the low-frequency
      noise when a single nanopore is measured multiple times. Differences up to 5
      orders of magnitude are found in the current power spectral density. In addition,
      we measure an unexpected double-peak ionic conductance profile. A simple model of
      a cylindrical nanopore that contains a nanobubble explains the measured profile
      and accounts for the observed variations in the magnitude of the conductance.

PMID- 17026339
TI  - Percolation and epidemic thresholds in clustered networks.
AB  - We develop a theoretical approach to percolation in random clustered networks. We
      find that, although clustering in scale-free networks can strongly affect some
      percolation properties, such as the size and the resilience of the giant
      connected component, it cannot restore a finite percolation threshold. In turn,
      this implies the absence of an epidemic threshold in this class of networks, thus
      extending this result to a wide variety of real scale-free networks which shows a
      high level of transitivity. Our findings are in good agreement with numerical
      simulations.

PMID- 17026340
TI  - Comment on "direct identification of critical clusters in chemical vapor
      deposition".

PMID- 17026342
TI  - Comment on "experimental observation of the 1/3 magnetization plateau in the
      diamond-chain compound Cu3(CO3)2(OH)2".

PMID- 17026344
TI  - Can one count the shape of a drum?
AB  - Sequences of nodal counts store information on the geometry (metric) of the
      domain where the wave equation is considered. To demonstrate this statement, we
      consider the eigenfunctions of the Laplace-Beltrami operator on surfaces of
      revolution. Arranging the wave functions by increasing values of the eigenvalues,
      and counting the number of their nodal domains, we obtain the nodal sequence
      whose properties we study. This sequence is expressed as a trace formula, which
      consists of a smooth (Weyl-like) part which depends on global geometrical
      parameters, and a fluctuating part, which involves the classical periodic orbits
      on the torus and their actions (lengths). The geometrical content of the nodal
      sequence is thus explicitly revealed.

PMID- 17026345
TI  - Bosonic molecules in rotating traps.
AB  - We present a variational many-body wave function for repelling bosons in rotating
      traps, focusing on rotational frequencies that do not lead to restriction to the
      lowest Landau level. This wave function incorporates correlations beyond the
      Gross-Pitaevskii (GP) mean-field approximation, and it describes rotating boson
      molecules (RBMs) made of localized bosons that form polygonal-ring-like
      crystalline patterns in their intrinsic frame of reference. The RBMs exhibit
      characteristic periodic dependencies of the ground-state angular momenta on the
      number of bosons in the polygonal rings. For small numbers of neutral bosons, the
      RBM ground-state energies are found to be always lower than those of the
      corresponding GP solutions, in particular, in the regime of GP vortex formation.

PMID- 17026346
TI  - Intermediate-temperature superfluidity in an atomic fermi gas with population
      imbalance.
AB  - We derive the underlying finite temperature theory which describes Fermi gas
      superfluidity with population imbalance in a homogeneous system. We compute the
      pair formation temperature, superfluid transition temperature Tc, and superfluid
      density in a manner consistent with the standard ground state equations and,
      thereby, present a complete phase diagram. Finite temperature stabilizes
      superfluidity, as manifested by two solutions for Tc or by low T instabilities.
      At unitarity, the polarized state is an "intermediate-temperature superfluid."

PMID- 17026347
TI  - Methods for scalable optical quantum computation.
AB  - We propose a scalable method for implementing linear optics quantum computation
      using the "linked-state" approach. Our method avoids the two-dimensional spread
      of errors occurring in the preparation of the linked state. Consequently, a proof
      is given for the scalability of this modified linked-state model, and an exact
      expression for the efficiency of the method is obtained. Moreover, a considerable
      improvement in the efficiency, relative to the original linked-state method, is
      achieved. The proposed method is applicable to Nielsen's optical "cluster-state"
      approach as well.

PMID- 17026348
TI  - Globally controlled quantum wires for perfect qubit transport, mirroring, and
      computing.
AB  - We describe a new design for a q wire with perfect transmission using a uniformly
      coupled Ising spin chain subject to global pulses. In addition to allowing for
      the perfect transport of single qubits, the design also yields the perfect
      "mirroring" of multiply encoded qubits within the wire. We further utilize this
      global-pulse generated perfect mirror operation as a "clock cycle" to perform
      universal quantum computation on these multiply encoded qubits where the interior
      of the q wire serves as the quantum memory while the q-wire ends perform one- and
      two-qubit gates.

PMID- 17026349
TI  - Toy model of hydrodynamic fluctuations.
AB  - We study hydrodynamic fluctuations in an ideal gas. Because one is interested in
      thermodynamic properties of small volume elements, Einstein's theory of
      equilibrium fluctuations in large systems is insufficient. A toy model of
      correlated fluctuations in neighboring small cells leads us to the distinction of
      biased and unbiased momentum densities. Hydrodynamic equations that satisfy the
      fluctuation-dissipation theorem can then be formulated in terms of these two
      different momentum densities or velocities.

PMID- 17026350
TI  - Active nematics are intrinsically phase separated.
AB  - Two-dimensional nonequilibrium nematic steady states, as found in agitated
      granular-rod monolayers or films of orientable amoeboid cells, were predicted
      [Europhys. Lett. 62, 196 (2003)10.1209/epl/i2003-00346-7] to have giant number
      fluctuations, with the standard deviation proportional to the mean. We show
      numerically that the steady state of such systems is macroscopically phase
      separated, yet dominated by fluctuations, as in the Das-Barma model [Phys. Rev.
      Lett. 85, 1602 (2000)10.1103/PhysRevLett.85.1602]. We suggest experimental tests
      of our findings in granular and living-cell systems.

PMID- 17026352
TI  - Neutrino signals from the formation of a black hole: A probe of the equation of
      state of dense matter.
AB  - The gravitational collapse of a nonrotating, black-hole-forming massive star is
      studied by nu-radiation-hydrodynamical simulations for two different sets of
      realistic equation of state of dense matter. We show that the event will produce
      as many neutrinos as the ordinary supernova, but with distinctive characteristics
      in luminosities and spectra that will be an unmistakable indication of black hole
      formation. More importantly, the neutrino signals are quite sensitive to the
      difference of equation of state and can be used as a useful probe into the
      properties of dense matter. The event will be unique in that they will be shining
      only by neutrinos (and, possibly, gravitational waves) but not by photons, and
      hence they should be an important target of neutrino astronomy.

PMID- 17026351
TI  - Reconstruction of complex dynamical systems affected by strong measurement noise.
AB  - This Letter reports on a new approach to properly analyze time series of
      dynamical systems which are spoilt by the simultaneous presence of dynamical
      noise and measurement noise. It is shown that even strong external measurement
      noise as well as dynamical noise which is an intrinsic part of the dynamical
      process can be quantified correctly, solely on the basis of measured time series
      and proper data analysis. Finally, real world data sets are presented pointing
      out the relevance of the new approach.

PMID- 17026353
TI  - Measuring the primordial deuterium abundance during the cosmic dark ages.
AB  - We discuss how measurements of fluctuations in the absorption of cosmic microwave
      background photons by neutral gas at redshifts z approximately 7-200 could reveal
      the primordial deuterium abundance of the Universe. The strength of the cross
      correlation of brightness-temperature fluctuations in the redshifted 21-cm line
      of hydrogen with those in the redshifted 92-cm line of deuterium is proportional
      to the value of the deuterium-to-hydrogen ratio [D/H] fixed during big bang
      nucleosynthesis. Although challenging, this measurement would provide the
      cleanest possible determination of [D/H], free from contamination by structure
      formation processes at lower redshifts. We additionally report our result for the
      thermal spin-change cross section in deuterium-hydrogen scattering.

PMID- 17026354
TI  - Holographic phase transitions with fundamental matter.
AB  - The holographic dual of a finite-temperature gauge theory with a small number of
      flavors typically contains D-brane probes in a black hole background. At low
      temperature, the branes sit outside the black hole and the meson spectrum is
      discrete and possesses a mass gap. As the temperature increases, the branes
      approach a critical solution. Eventually, they fall into the horizon and a phase
      transition occurs. In the new phase, the meson spectrum is continuous and
      gapless. At large Nc and large 't Hooft coupling, we show that this phase
      transition is always first order. In confining theories with heavy quarks, it
      occurs above the deconfinement transition for the glue.

PMID- 17026355
TI  - Low-energy dynamics in ultradegenerate QCD matter.
AB  - We study the low-energy behavior of QCD Green functions in the limit that the
      baryon chemical potential is much larger than the QCD scale parameter LambdaQCD.
      We show that there is a systematic low-energy expansion in powers of
      (omega/m)(1/3), where omega is the energy and m is the screening scale. This
      expansion is valid even if the effective quark-gluon coupling g is not small. The
      expansion is purely perturbative in the magnetic regime |k| >> k0. If the
      external momenta and energies satisfy |k| approximately k0, planar, Abelian
      ladder diagrams involving the full quark propagator have to be resummed but the
      corresponding Dyson-Schwinger equations are closed.

PMID- 17026356
TI  - Reduction of the spin-orbit splittings at the n = 28 shell closure.
AB  - The N = 28 shell closure has been investigated via the 46Ar(d,p)47Ar transfer
      reaction in inverse kinematics. Energies and spectroscopic factors of the neutron
      p(3/2), p(1/2), and f(5/2) states in 47Ar were determined and compared to those
      of the 49Ca isotone. We deduced a reduction of the N = 28 gap by 330(90) keV and
      spin-orbit weakenings of approximately 10(2) and 45(10)% for the f and p states,
      respectively. Such large variations for the f and p spin-orbit splittings could
      be accounted for by the proton-neutron tensor force and by the density dependence
      of the spin-orbit interaction, respectively. This contrasts with the picture of
      the spin-orbit interaction as a surface term only.

PMID- 17026357
TI  - Enhanced effect of temporal variation of the fine structure constant and the
      strong interaction in 229Th.
AB  - The relative effects of the variation of the fine structure constant alpha =
      e2/variant Planck's over 2pi c and the dimensionless strong interaction parameter
      m(q)/LambdaQCD are enhanced by 5-6 orders of magnitude in a very narrow
      ultraviolet transition between the ground and the first excited states in the
      229Th nucleus. It may be possible to investigate this transition with laser
      spectroscopy. Such an experiment would have the potential of improving the
      sensitivity to temporal variation of the fundamental constants by many orders of
      magnitude.

PMID- 17026358
TI  - Symmetry of carrier-envelope phase difference effects in strong-field, few-cycle
      ionization of atoms and molecules.
AB  - In few-cycle pulses, the exact value of the carrier-envelope phase difference
      (CEPD) has a pronounced influence on the ionization dynamics of atoms and
      molecules. We show that, for atoms in circularly polarized light, a change in the
      CEPD is mapped uniquely to an overall rotation of the system, and results for
      arbitrary CEPD are obtained by rotation of the results from a single calculation
      with fixed CEPD. For molecules, this is true only for linear molecules aligned
      parallel with the propagation direction of the field. The effects of CEPD are
      classified as geometric or nongeometric. The observations are exemplified by
      strong-field calculations on hydrogen.

PMID- 17026359
TI  - Low velocity quantum reflection of Bose-Einstein condensates.
AB  - We study how interactions affect the quantum reflection of Bose-Einstein
      condensates. A patterned silicon surface with a square array of pillars resulted
      in high reflection probabilities. For incident velocities greater than 2.5 mm/s,
      our observations agreed with single-particle theory. At velocities below 2.5
      mm/s, the measured reflection probability saturated near 60% rather than
      increasing towards unity as predicted by the accepted theoretical model. We
      extend the theory of quantum reflection to account for the mean-field
      interactions of a condensate which suppresses quantum reflection at low velocity.
      The reflected condensates show collective excitations as recently predicted.

PMID- 17026360
TI  - Unexpected higher-order effects in charged particle impact ionization at high
      energies.
AB  - Most of the experimental and theoretical studies of electron-impact ionization of
      atoms, referred to as (e, 2e), have concentrated on the scattering plane. The
      assumption has been that all the important physical effects will be observable in
      the scattering plane. However, very recently it has been shown that, for C6+
      helium ionization, experiment and theory are in nice agreement in the scattering
      plane and in very bad agreement out of the scattering plane. This lack of
      agreement between experiment and theory has been explained in terms of higher
      order scattering effects between the projectile and target ion. We have examined
      electron-impact ionization of magnesium and have observed similar higher-order
      effects. The results of the electron-impact ionization of magnesium indicate the
      possible deficiencies in the calculation of fully differential cross sections in
      previous heavy particle ionization work.

PMID- 17026361
TI  - Spontaneous emission of an atom in a cavity with nonorthogonal eigenmodes.
AB  - The spontaneous emission of an excited atom in a lossy cavity with nonorthogonal
      eigenmodes is analyzed. The quantum Langevin formalism is used to describe the
      dynamics of the spontaneous decay. The analysis shows that the spontaneous decay
      is modified by the Q value and the effective mode volume factor of each cavity
      eigenmode. The effective mode volume is generalized for cavities with
      nonorthogonal modes, which can be a very significant modification in the
      microcavity regime. It is shown that the spontaneous decay is not enhanced by the
      excess noise factor as claimed by other analyses.

PMID- 17026362
TI  - Stable control of pulse speed in parametric three-wave solitons.
AB  - We analyze the control of the propagation speed of three wave packets interacting
      in a medium with quadratic nonlinearity and dispersion. We find analytical
      expressions for mutually trapped pulses with a common velocity in the form of a
      three-parameter family of solutions of the three-wave resonant interaction. The
      stability of these novel parametric solitons is simply related to the value of
      their common group velocity.

PMID- 17026363
TI  - Mode-coupling control in resonant devices: Application to solid-state ring
      lasers.
AB  - We report the theoretical and experimental investigation of the effects of mode
      coupling in a resonant macroscopic quantum device, in the case of a solid-state
      ring laser. This is achieved by introducing an additional coupling source whose
      interplay with the already-existing nonlinear effects ensures the coexistence of
      two counterpropagating cavity modes yielding a rotation-sensitive beat note. The
      determination of the condition for rotation sensing, both theoretically and
      experimentally, allows a quantitative study of the role of various mode-coupling
      mechanisms, in particular, the gain-induced mode coupling. We point out the
      connection between our work and the theoretical work on mode coupling in
      superfluid devices. This work opens up the possibility of new types of active
      rotation sensors.

PMID- 17026364
TI  - Bistable phase locking of a nonlinear optical cavity via rocking: Transmuting
      vortices into phase patterns.
AB  - We report the experimental observation of the conversion of a phase-invariant
      nonlinear system into a bistable phase-locked one via rocking [G. J. de Valcarcel
      and K. Staliunas, Phys. Rev. E 67, 026604 (2003)10.1103/PhysRevE.67.026604]. This
      conversion results in vortices of the phase-invariant system being replaced by
      phase patterns such as domain walls. A model for the experimental device, a
      photorefractive oscillator, is given that reproduces the observed behavior.

PMID- 17026365
TI  - Scarring by homoclinic and heteroclinic orbits.
AB  - In addition to the well-known scarring effect of periodic orbits, we show here
      that homoclinic and heteroclinic orbits, which are cornerstones in the theory of
      classical chaos, also scar eigenfunctions of classically chaotic systems when
      associated closed circuits in phase space are properly quantized, thus
      introducing strong quantum correlations. The corresponding quantization rules are
      also established. This opens the door for developing computationally tractable
      methods to calculate eigenstates of chaotic systems.

PMID- 17026366
TI  - Characterizing the dynamical importance of network nodes and links.
AB  - The largest eigenvalue of the adjacency matrix of networks is a key quantity
      determining several important dynamical processes on complex networks. Based on
      this fact, we present a quantitative, objective characterization of the dynamical
      importance of network nodes and links in terms of their effect on the largest
      eigenvalue. We show how our characterization of the dynamical importance of nodes
      can be affected by degree-degree correlations and network community structure. We
      discuss how our characterization can be used to optimize techniques for
      controlling certain network dynamical processes and apply our results to real
      networks.

PMID- 17026367
TI  - Thermal rectification in billiardlike systems.
AB  - We study the thermal rectification phenomenon in billiard systems with
      interacting particles. This interaction induces a local dynamical response of the
      billiard to an external thermodynamic gradient. To explain this dynamical effect
      we study the steady state of an asymmetric billiard in terms of the particle and
      energy reflection coefficients. This allows us to obtain expressions for the
      region in parameter space where large thermal rectifications are expected. Our
      results are confirmed by extensive numerical simulations.

PMID- 17026368
TI  - Instability and evolution of nonlinearly interacting water waves.
AB  - We consider the modulational instability of nonlinearly interacting two
      dimensional waves in deep water, which are described by a pair of two-dimensional
      coupled nonlinear Schrodinger equations. We derive a nonlinear dispersion
      relation. The latter is numerically analyzed to obtain the regions and the
      associated growth rates of the modulational instability. Furthermore, we follow
      the long term evolution of the latter by means of computer simulations of the
      governing nonlinear equations and demonstrate the formation of localized coherent
      wave envelopes. Our results should be useful for understanding the formation and
      nonlinear propagation characteristics of large-amplitude freak waves in deep
      water.

PMID- 17026369
TI  - Cavitation bubble dynamics inside liquid drops in microgravity.
AB  - We studied spark-generated cavitation bubbles inside water drops produced in
      microgravity. High-speed visualizations disclosed unique effects of the spherical
      and nearly isolated liquid volume. In particular, (1) toroidally collapsing
      bubbles generate two liquid jets escaping from the drop, and the "splash jet"
      discloses a remarkable broadening. (2) Shock waves induce a strong form of
      secondary cavitation due to the particular shock wave confinement. This feature
      offers a novel way to estimate integral shock wave energies in isolated volumes.
      (3) Bubble lifetimes in drops are shorter than in extended volumes in remarkable
      agreement with herein derived corrective terms for the Rayleigh-Plesset equation.

PMID- 17026370
TI  - Trapped-particle-mediated collisional damping of nonaxisymmetric plasma waves.
AB  - Weak axial variations in magnetic or electric confinement fields in pure electron
      plasmas cause slow electrons to be trapped locally, and collisional diffusion
      across the trapping separatrix then causes surprisingly large trapped-particle
      mediated (TPM) damping and transport effects. Here we characterize TPM damping of
      m theta not equal to 0, m(z) = +/-1 Trivelpiece-Gould plasma modes in large
      amplitude long-lived Bernstein-Greene-Kruskal states. The TPM damping gives
      gammaBGK/omega approximately 10(-4) and seems to dominate in regimes of weak
      interparticle collisions.

PMID- 17026371
TI  - Observation of instability-induced current redistribution in a spherical-torus
      plasma.
AB  - A motional Stark effect diagnostic has been utilized to reconstruct the parallel
      current density profile in a spherical-torus plasma for the first time. The
      measured current profile compares favorably with neoclassical theory when no
      large-scale magnetohydrodynamic instabilities are present in the plasma. However,
      a current profile anomaly is observed during saturated interchange-type
      instability activity. This apparent anomaly can be explained by redistribution of
      neutral beam injection current drive and represents the first observation of
      interchange-type instabilities causing such redistribution. The associated
      current profile modifications contribute to sustaining the central safety factor
      above unity for over five resistive diffusion times, and similar processes may
      contribute to improved operational scenarios proposed for ITER.

PMID- 17026372
TI  - Experimental confirmation of stable, small-debye-length, pure-electron-plasma
      equilibria in a stellarator.
AB  - The creation of the first small-Debye length, low temperature pure electron
      plasmas in a stellarator is reported. A confinement time of 20 ms has been
      measured. The long confinement time implies the existence of macroscopically
      stable equilibria and that the single particle orbits are well confined despite
      the lack of quasisymmetry in the device, the Columbia non-neutral torus. This
      confirms the beneficial confinement effects of strong electric fields and the
      resulting rapid E x B rotation of the electrons. The particle confinement time is
      presently limited by the presence of bulk insulating materials in the plasma,
      rather than any intrinsic plasma transport processes. A nearly flat temperature
      profile is seen in the inner part of the plasma.

PMID- 17026373
TI  - Surface acceleration of fast electrons with relativistic self-focusing in
      preformed plasma.
AB  - We report an observation of surface acceleration of fast electrons in intense
      laser-plasma interactions. When a preformed plasma is presented in front of a
      solid target with a higher laser intensity, the emission direction of fast
      electrons is changed to the target surface direction from the laser and specular
      directions. This feature could be caused by the formation of a strong static
      magnetic field along the target surface which traps and holds fast electrons on
      the surface. In our experiment, the increase in the laser intensity due to
      relativistic self-focusing in plasma plays an important role for the formation.
      The strength of the magnetic field is calculated from the bent angle of the
      electrons, resulting in tens of percent of laser magnetic field, which agrees
      well with a two-dimensional particle-in-cell calculation. The strong surface
      current explains the high conversion efficiency on the cone-guided fast ignitor
      experiments.

PMID- 17026374
TI  - Exotic behavior of hydrogen atoms in solid H2 at temperatures below 1 K.
AB  - We present the first magnetic resonance study of atomic hydrogen embedded in
      solid H2 films for temperatures 150-900 mK. We found that at T approximately 150
      mK average concentrations of H atoms of order 10(18 cm(-3) are very stable
      against recombination during two weeks of observations. The distribution of the
      population of the two lowest hyperfine states is found to be non-Boltzmann, with
      a very large occupation of the ground state. We consider the possibility of
      formation in solid H2 of regions with high local concentrations of H atoms, where
      collective quantum phenomena might occur.

PMID- 17026375
TI  - Bulk-driven nonequilibrium phase transitions in a mesoscopic ring.
AB  - We study a periodic one-dimensional exclusion process composed of a driven and a
      diffusive part. In a mesoscopic limit where both dynamics compete we identify
      bulk-driven phase transitions. We employ mean-field theory complemented by Monte
      Carlo simulations to characterize the emerging nonequilibrium steady states.
      Monte Carlo simulations reveal interesting correlation effects that we explain
      phenomenologically.

PMID- 17026376
TI  - Cooperativity beyond caging: Generalized mode-coupling theory.
AB  - The validity of mode-coupling theory (MCT) is restricted by an uncontrolled
      factorization approximation of density correlations. The factorization can be
      delayed and ultimately avoided, however, by explicitly including higher order
      correlations. We explore this approach within a microscopically motivated
      schematic model. Analytic tractability allows us to discuss in great detail the
      impact of factorization at arbitrary order, including the limit of avoided
      factorization. Our results indicate a coherent picture for the capabilities as
      well as limitations of MCT. Moreover, including higher order correlations
      systematically defers the transition and ultimately restores ergodicity. Power
      law divergence of the relaxation time is then replaced by continuous but
      exponential growth.

PMID- 17026377
TI  - Nonlinear dielectric response and thermodynamic heterogeneity in liquids.
AB  - If large amplitude time-dependent fields (e.g., dielectric, magnetic, mechanical)
      are applied to a sample that displays relaxational modes, some energy of the
      external field is absorbed by the slow degrees of freedom. The weak coupling of
      these modes to the phonon bath leads to long persistence times of the resulting
      higher fictive temperature. Assuming heterogeneities regarding dielectric and
      thermal relaxation times, extremely strong nonlinear dielectric effects are
      predicted and experimentally verified. For glycerol at T = 213 K, the dielectric
      loss measured at 280 kV/cm increases by more than 6% over its low-field value.
      This nonlinearity shows a characteristic frequency dependence and implies that
      dielectric and thermal time constants are locally correlated in viscous liquids.

PMID- 17026378
TI  - How does crystalline substrate plasticity modify thin film buckling?
AB  - We report experimental atomic force microscopy observations and analytical
      modeling of buckling structures of thin films deposited on single crystal
      substrates. The formation of straight-sided blisters just above the step
      structures resulting from the dislocations emergence has been observed and
      explained in the framework of the Foppl-von Karman theory of thin plates. A
      critical step height above which the buckling may occur has been determined and
      the asymmetry of the resulting blisters has been explained. Finally, the new
      buckling criterion has been compared with the classical one in the plane case and
      allows us to explain the blisters localization on step structures.

PMID- 17026379
TI  - Continuum theory of nanostructure decay via a microscale condition.
AB  - The morphological relaxation of faceted crystal surfaces is studied via a
      continuum approach. Our formulation includes (i) an evolution equation for the
      surface slope that describes step line tension, g1, and step repulsion energy,
      g3; and (ii) a condition at the facet edge (a free boundary) that accounts for
      discrete effects via the collapse times, t(n), of top steps. For initial cones
      and t(n) approximately t(n)4, we use t(g) from step simulations and predict self
      similar slopes in agreement with simulations for any g = g3/g1 > 0. We show that
      for g >> 1, (i) the theory simplifies to an equilibrium-thermodynamics model;
      (ii) the slope profiles reduce to a universal curve; and (iii) the facet radius
      scales as g(-3/4).

PMID- 17026380
TI  - Excitonic effects and optical properties of passivated CdSe clusters.
AB  - We calculate the optical properties of a series of passivated nonstoichiometric
      CdSe clusters using two first-principles approaches: time-dependent density
      functional theory within the local-density approximation, and by solving the
      Bethe-Salpeter equation for optical excitations with the GW approximation for the
      self-energy. We analyze the character of optical excitations leading to the first
      low-energy peak in the absorption cross section of these clusters. Within time
      dependent density functional theory, we find that the lowest-energy excitation is
      mostly a single-level to single-level transition. In contrast, many-body methods
      predict a strong mixture of several different transitions, which is a signature
      of excitonic effects. The majority of the clusters have a series of dark
      transitions before the first bright transition. This may explain the long
      radiative lifetimes observed experimentally.

PMID- 17026381
TI  - Energy- and momentum-resolved exchange and spin-orbit interaction in cobalt film
      by spin-polarized two-electron spectroscopy.
AB  - Spontaneous ordering of electronic spins in ferromagnetic materials is one of the
      best known and most studied examples of quantum correlations. Exchange
      correlations are responsible for long range spin order and the spin-orbit
      interaction (SOI) can create preferred crystalline directions for the spins,
      i.e., magnetic anisotropy. Presented experimental data illustrate how novel spin
      polarized two-electron spectroscopy in-reflection mode allows observation of the
      localization of spin-dependent interactions in energy-momentum space. Comparison
      of spin-orbit asymmetries in spectra of Co film and clean W(110) may indicate the
      presence of interface specific proximity effects providing important clues to the
      formation of preferred orientations for the magnetic moment of the Co film. These
      results may help to understand the microscopic origin of interface magnetic
      anisotropy.

PMID- 17026382
TI  - Coulomb blockade and transport in a chain of one-dimensional quantum dots.
AB  - A long one-dimensional wire with a finite density of strong random impurities is
      modeled as a chain of weakly coupled quantum dots. At low temperature T and
      applied voltage V its resistance is limited by breaks: randomly occurring
      clusters of quantum dots with a special length distribution pattern that inhibit
      the transport. Because of the interplay of interaction and disorder effects the
      resistance can exhibit T and V dependences that can be approximated by power
      laws. The corresponding two exponents differ greatly from each other and depend
      not only on the intrinsic electronic parameters but also on the impurity
      distribution statistics.

PMID- 17026383
TI  - Controlled flow of spin-entangled electrons via adiabatic quantum pumping.
AB  - We propose a method to dynamically generate and control the flow of spin
      entangled electrons, each belonging to a spin singlet, by means of adiabatic
      quantum pumping. The pumping cycle functions by periodic time variation of
      localized two-body interactions. We develop a generalized approach to adiabatic
      quantum pumping as traditional methods based on a scattering matrix in one
      dimension cannot be applied here. We specifically compute the flow of spin
      entangled electrons within a Hubbard-like model of quantum dots, discuss possible
      implementations, and identify parameters that can be used to control the singlet
      flow.

PMID- 17026384
TI  - Zero-field kondo splitting and quantum-critical transition in double quantum
      dots.
AB  - Double quantum dots offer unique possibilities for the study of many-body
      correlations. A system containing one Kondo dot and one effectively
      noninteracting dot maps onto a single-impurity Anderson model with a structured
      (nonconstant) density of states. Numerical renormalization-group calculations
      show that, while band filtering through the resonant dot splits the Kondo
      resonance, the singlet ground state is robust. The system can also be
      continuously tuned to create a pseudogapped density of states and access a
      quantum-critical point separating Kondo and non-Kondo phases.

PMID- 17026385
TI  - Optical conductivity of a two-dimensional electron liquid with spin-orbit
      interaction.
AB  - The interplay of electron-electron interactions and spin-orbit coupling leads to
      a new contribution to the homogeneous optical conductivity of the electron
      liquid. The latter is known to be insensitive to many-body effects for a
      conventional electron system with parabolic dispersion. The parabolic spectrum
      has its origin in the Galilean invariance which is broken by spin-orbit coupling.
      This opens up a possibility for the optical conductivity to probe electron
      electron interactions. We analyze the interplay of interactions and spin-orbit
      coupling and obtain optical conductivity beyond RPA.

PMID- 17026386
TI  - Generating spin currents in semiconductors with the spin Hall effect.
AB  - We investigate electrically induced spin currents generated by the spin Hall
      effect in GaAs structures that distinguish edge effects from spin transport.
      Using Kerr rotation microscopy to image the spin polarization, we demonstrate
      that the observed spin accumulation is due to a transverse bulk electron spin
      current, which can drive spin polarization nearly 40 microns into a region in
      which there is minimal electric field. Using a model that incorporates the
      effects of spin drift, we determine the transverse spin drift velocity from the
      magnetic field dependence of the spin polarization.

PMID- 17026387
TI  - First-principles calculation of alloy scattering in Ge(x)Si(1-x).
AB  - First-principles electronic structure methods are used to find the rates of
      intravalley and intervalley n-type carrier scattering due to alloy disorder in
      Si(1-x)Ge(x) alloys. The required alloy scattering matrix elements are calculated
      from the energy splitting of nearly degenerate Bloch states which arises when one
      average host atom is replaced by a Ge or Si atom in supercells containing up to
      128 atoms. Scattering parameters for all relevant Delta and L intravalley and
      intervalley alloy scattering are calculated. Atomic relaxation is found to have a
      substantial effect on the scattering parameters. f-type intervalley scattering
      between Delta valleys is found to be comparable to other scattering channels. The
      n-type carrier mobility, calculated from the scattering rate using the Boltzmann
      transport equation in the relaxation time approximation, is in excellent
      agreement with experiments on bulk, unstrained alloys.

PMID- 17026388
TI  - Resonantly enhanced nonlinear conductance in long quantum point contacts near
      pinch-off.
AB  - We report on a remarkable resonance in the differential conductance of long
      quantum point contacts (QPCs) that is observed as a precursor to regular
      quantized transport. This effect is increasingly pronounced in longer QPCs, in
      which the differential conductance may resonantly exceed 2e2/h. From a study of
      the experimental characteristics of this feature, we suggest that it may be
      associated with the formation of a well-resolved energy gap that opens
      dynamically as a result of enhanced many-body interactions in long QPCs.

PMID- 17026389
TI  - Phase-charge duality of a josephson junction in a fluctuating electromagnetic
      environment.
AB  - We have measured the current-voltage characteristics of a single Josephson
      junction placed in a high impedance environment. The transfer of Cooper pairs
      through the junction is governed by overdamped quasicharge dynamics, leading to
      Coulomb blockade and Bloch oscillations. Exact duality exists to the standard
      overdamped phase dynamics of a Josephson junction, resulting in a dual shape of
      the current-voltage characteristic, with current and voltage changing roles. We
      demonstrate this duality with experiments which allow for a quantitative
      comparison with a theory that includes the effect of fluctuations due to the
      finite temperature of the electromagnetic environment.

PMID- 17026390
TI  - Variable orbital coupling in a two-dimensional quantum-dot solid probed on a
      local scale.
AB  - The optoelectronic properties of semiconductor quantum-dot (QD) solids depend on
      the electronic structure of the building blocks and their interactions. Disorder
      may affect the coupling on a local scale. We have measured the density of states
      of 2D arrays of PbSe QDs site by site using scanning tunneling spectroscopy. It
      markedly differs from that of isolated QDs due to electronic coupling in the
      array. We observe strong local variations in the coupling strength with two
      prototypical cases: delocalization of the conduction electrons only, and full
      coupling with both hole and electron delocalization over the QD sites in the
      array.

PMID- 17026392
TI  - Spin excitations in fluctuating stripe phases of doped cuprate superconductors.
AB  - Using a phenomenological lattice model of coupled spin and charge modes, we
      determine the spin susceptibility in the presence of fluctuating stripe charge
      order. We assume the charge fluctuations to be slow compared to those of the
      spins, and combine Monte Carlo simulations for the charge order parameter with
      exact diagonalization of the spin sector. Our calculations unify the spin
      dynamics of both static and fluctuating stripe phases and support the notion of a
      universal spin excitation spectrum in doped cuprate superconductors.

PMID- 17026391
TI  - Electron-magnon coupling and nonlinear tunneling transport in magnetic
      nanoparticles.
AB  - We present a theory of single-electron tunneling transport through a
      ferromagnetic nanoparticle in which particle-hole excitations are coupled to spin
      collective modes. The model employed to describe the interaction between
      quasiparticles and collective excitations captures the salient features of a
      recent microscopic study. Our analysis of nonlinear quantum transport in the
      regime of weak coupling to the external electrodes is based on a rate-equation
      formalism for the nonequilibrium occupation probability of the nanoparticle many
      body states. For strong electron-boson coupling, we find that the tunneling
      conductance as a function of bias voltage is characterized by a large and dense
      set of resonances. Their magnetic field dependence in the large-field regime is
      linear, with slopes of the same sign. Both features are in agreement with recent
      tunneling experiments.

PMID- 17026393
TI  - Low-energy electrodynamics of superconducting diamond.
AB  - Heavily boron-doped, diamond films can become superconducting with critical
      temperatures Tc well above 4 K. Here we first measure the reflectivity of such a
      film down to 5 cm(-1), by also using coherent synchrotron radiation. We thus
      determine the optical gap 2Delta, the field penetration depth lambda, the range
      of action of the Ferrell-Glover-Tinkham sum rule, and the electron-phonon
      spectral function alpha2F(omega). We conclude that diamond behaves as a dirty BCS
      superconductor.

PMID- 17026394
TI  - Organometallic benzene-vanadium wire: A one-dimensional half-metallic
      ferromagnet.
AB  - Using density functional theory we perform theoretical investigations of the
      electronic properties of a freestanding one-dimensional organometallic vanadium
      benzene wire. This system represents the limiting case of multidecker
      Vn(C6H6)(n+1) clusters which can be synthesized with established methods. We
      predict that the ground state of the wire is a 100% spin-polarized ferromagnet
      (half-metal). Its density of states is metallic at the Fermi energy for the
      minority electrons and shows a semiconductor gap for the majority electrons. We
      find that the half-metallic behavior is conserved up to 12% longitudinal
      elongation of the wire. Ab initio electron transport calculations reveal that
      finite size vanadium-benzene clusters coupled to ferromagnetic Ni or Co
      electrodes will work as nearly perfect spin filters.

PMID- 17026395
TI  - Interface coupling transition in a thin epitaxial antiferromagnetic film
      interacting with a ferromagnetic substrate.
AB  - We report experimental evidence for a transition in the interface coupling
      between an antiferromagnetic film and a ferromagnetic substrate. The transition
      is observed in a thin epitaxial NiO film grown on top of Fe(001) as the film
      thickness is increased. Photoemission electron microscopy excited with linearly
      polarized x rays shows that the NiO film is antiferromagnetic at room temperature
      with in-plane uniaxial magnetic anisotropy. The anisotropy axis is perpendicular
      to the Fe substrate magnetization when the NiO thickness is less than about 15 A,
      but rapidly becomes parallel to the Fe magnetization for a NiO coverage higher
      than 25 A.

PMID- 17026396
TI  - Ferroelectric polarization flop in a frustrated magnet MnWO4 induced by a
      magnetic field.
AB  - The relationship between magnetic order and ferroelectric properties has been
      investigated for MnWO4 with a long-wavelength magnetic structure. Spontaneous
      electric polarization is observed in an elliptical spiral spin phase. The
      magnetic-field dependence of electric polarization indicates that the
      noncollinear spin configuration plays a key role for the appearance of the
      ferroelectric phase. An electric polarization flop from the b direction to the a
      direction has been observed when a magnetic field above 10 T is applied along the
      b axis. This result demonstrates that an electric polarization flop can be
      induced by a magnetic field in a simple system without rare-earth 4f moments.

PMID- 17026397
TI  - Lattice disorder and size-induced kondo behavior in CeAl2 and CePt(2+x).
AB  - When the size of CeAl2 and CePt(2+x) particles is reduced to the nanometer scale,
      antiferromagnetism is suppressed and Kondo behavior predominates, with the Kondo
      temperature T(K) either decreasing (CeAl2) or increasing (CePt(2+x)) relative to
      the bulk. Local structure measurements show that these nanoparticles are
      significantly distorted. While such distortions should strongly affect magnetic
      and electronic properties, we find they cannot explain the observed changes in
      T(K). Other size-induced changes to the electronic structure must, therefore,
      play a significant role.

PMID- 17026398
TI  - Spin transfer in magnetic tunnel junctions with hot electrons.
AB  - Recent data on the bias dependence of the spin transfer effect in magnetic tunnel
      junctions have shown that torque remains intact at bias voltages for which the
      tunneling magnetoresistance has been strongly reduced. We show that the current
      induced excitations due to hot electrons, while reducing the magnetoresistance,
      enhance both the charge current and the spin transfer in magnetic tunnel
      junctions in such a manner that the ratio of the torque to the charge current
      does not significantly change.

PMID- 17026399
TI  - Long-range spin-qubit interaction mediated by microcavity polaritons.
AB  - We study the optically induced coupling between spins mediated by polaritons in a
      planar microcavity. In the strong-coupling regime, the vacuum Rabi splitting
      introduces anisotropies in the spin coupling. Moreover, due to their photonlike
      mass, polaritons provide an extremely long spin coupling range. This suggests the
      realization of two-qubit all-optical quantum operations within tens of
      picoseconds with spins localized as far as hundreds of nanometers apart.

PMID- 17026400
TI  - Dominant effect of polariton-polariton interactions on the coherence of the
      microcavity optical parametric oscillator.
AB  - The importance of interaction effects in determining the temporal coherence of
      spectrally and spatially isolated single modes of the microcavity optical
      parametric oscillator (OPO) is demonstrated. As a function of macroscopic
      occupancy, the coherence time (tau c) first increases linearly and then exhibits
      saturation behavior, reaching maximum values of up to 500 ps. Good agreement is
      found with a model including fluctuations in polariton number and polariton
      polariton interactions between the OPO states. tau c is a property of the coupled
      OPO system, a result confirmed by the finding of equal coherence times for signal
      and idler, even though the idler is subject to strong additional scattering.

PMID- 17026401
TI  - Attraction between like-charged walls: Short-ranged simulations using local
      molecular field theory.
AB  - Effective attraction between like-charged walls mediated by counterions is
      studied using local molecular field (LMF) theory. Monte Carlo simulations of the
      "mimic system" given by LMF theory, with short-ranged "Coulomb core" interactions
      in an effective single particle potential incorporating a mean-field average of
      the long-ranged Coulomb interactions, provide a direct test of the theory, and
      are in excellent agreement with more complex simulations of the full Coulomb
      system by Moreira and Netz [Eur. Phys. J. E 8, 33 (2002)]. A simple, generally
      applicable criterion to determine the consistency parameter sigma(min) needed for
      accurate use of the LMF theory is presented.

PMID- 17026402
TI  - Vortex flow in freestanding smectic films driven by elastic relaxation of the c
      director.
AB  - We report a simple experiment in freestanding smectic films in which elastic
      distortions of the c director drive macroscopic flow. The flow field is
      visualized with tracer particles. Measurements are compared to predictions of a
      model that employs the coupled dynamic equations for director and velocity
      fields. Relaxation dynamics depends on the topology of the film center: for
      defect-free target patterns, shear flow provides the dominating contribution to
      the c director dynamics. In presence of a central topological defect of strength
      S = + 1, the influence of flow on the relaxation dynamics is practically
      negligible, while for a central S = - 1 defect, the influence of vortex flow on
      the c-director relaxation is roughly twice as large as for the defect-free state.

PMID- 17026403
TI  - Superlattice formation in a binary mixture of block copolymer micelles.
AB  - A binary solution mixture of distinct block copolymer micelles is found to adopt
      a superlattice. The larger micelles, formed from polystyrene-polyisoprene
      diblocks, have a nominal radius of 29 nm; the smaller micelles, formed from
      polystyrene-polydimethylsiloxane diblocks, have a nominal radius of 16 nm. The
      superlattice unit cell dimension is 156 nm and is assigned to space group Fm3c;
      it corresponds to the AB13 structure. As these diblocks are uncharged, the
      driving force for superlattice formation is primarily free volume entropy, as in
      sterically stabilized colloidal hard spheres.

PMID- 17026405
TI  - Fisher information for spike-based population decoding.
AB  - We evaluate the Fisher information of a population of model neurons that receive
      dynamical input and interact via spikes. With spatially independent threshold
      noise, the spike-based Fisher information that summarizes the information carried
      by individual spike timings has a particularly simple analytical form. We
      calculate the loss of information caused by abandoning spike timing and study the
      effect of synaptic connections on the Fisher information. For a simple
      spatiotemporal input, we derive the optimal recurrent connectivity that has a
      local excitation and global inhibition structure. The optimal synaptic
      connections depend on the spatial or temporal feature of the input that the
      system is designed to code.

PMID- 17026404
TI  - Stall, spiculate, or run away: The fate of fibers growing towards fluctuating
      membranes.
AB  - We study the dynamics of a growing semiflexible fiber approaching a membrane at
      an angle. At late times we find three regimes: fiber stalling, when growth stops,
      runaway, in which the fiber bends away from the membrane, and another regime in
      which spicules form. We discuss which regions of the resulting "phase diagram"
      are explored by (i) single and bundled actin fibers in living cells, (ii) sickle
      hemoglobin fibers, and (iii) microtubules inside vesicles. We complement our
      analysis with 3D stochastic simulations.

PMID- 17026406
TI  - Negative tension induced by lipid uptake.
AB  - Membrane fusion is an important process in cell biology. While the molecular
      mechanisms of fusion are actively studied at a very local scale, the consequences
      of fusion at a larger scale on the shape and stability of the membrane are still
      not explored. In this Letter, the evolution of the membrane tension during the
      fusion of positive small unilamellar vesicles with a negative giant unilamellar
      vesicle has been experimentally investigated and compared to an existing
      theoretical model. The tension has been deduced using videomicroscopy from the
      measurement of the fluctuation spectrum and of the time correlation function of
      the fluctuations. We show that fusion induces a strong decrease in the effective
      tension of the membrane which eventually reaches negative values. Under these
      conditions, we show that localized instabilities appear on the vesicle. The
      membrane finally collapses, forming dense lipid structures.

PMID- 17026407
TI  - Nanophase-separated synchronizing structure with parallel double periodicity from
      an undecablock terpolymer.
AB  - A new nanophase-separated structure with parallel double periodicity has been
      identified for an undecablock terpolymer in bulk. The polymer includes two long
      poly(2-vinypyridine) (P) chains on each end, with five short polyisoprene (I) and
      four short polystyrene (S) chains at the center. This polymer exhibits a
      hierarchical lamellar structure with two crystallographic periods: 88 nm and 16
      nm. The 88 nm period includes one thick P lamella and five thin I-S-I-S-I
      lamellae, of extremely high orientation.

PMID- 17026408
TI  - Additive decomposition of shear strength in cohesive granular media from grain
      scale interactions.
AB  - We study cemented granular media by introducing cohesive bonding (sliding or
      rolling friction and tensile strength) between grains in the framework of the
      contact dynamics method. We find that, for a wide range of bond parameters, the
      macroscopic angle of friction at the peak state can be split into three distinct
      terms of collisional, frictional and dilational origins. Remarkably, the
      macroscopic tensile strength depends only on the bond tensile strength, and the
      friction angle at the peak state is proportional to the dilatancy angle which
      varies linearly with sliding friction.

PMID- 17026409
TI  - Screening and fundamental length scales in semidilute Na-DNA aqueous solutions.
AB  - The fundamental length scales in semidilute Na-DNA aqueous solutions have been
      investigated by dielectric spectroscopy. The low- and the high-frequency
      relaxation modes are studied in detail. The length scale of the high-frequency
      relaxation mode at high DNA concentrations can be identified with the de Gennes
      Pfeuty-Dobrynin correlation length of polyelectrolytes in semidilute solution,
      whereas at low DNA concentrations and in the low added salt limit the length
      scale shows an unusual exponent reminiscent of semidilute polyelectrolyte chains
      with hydrophobic backbone. The length scale of the low-frequency relaxation mode
      corresponds to a Gaussian chain composed of correlation blobs in the low added
      salt limit, and to the Odijk-Skolnick-Fixman value of the single chain
      persistence length in the high added salt limit.

PMID- 17026410
TI  - Measuring the force of interaction between a metallic probe and a single
      molecule.
AB  - Precision current measurements are recorded at 5 K during the approach and
      contact between a Pt-inked probe and the carbon-carbon double-bond region of an
      isolated 1,3-cyclohexadiene molecule chemisorbed on a Si(100) surface. Scanning
      tunneling spectroscopic data reveal systematic features in the current at
      specific probe-molecule separations. Aided by density functional theory
      calculations, we show that these features arise from interaction forces between
      the probe and molecule, which can be interpreted as the relaxation of the probe
      molecule system prior to and during contact.

PMID- 17026411
TI  - Increasing primary care physician productivity: A case study.
AB  - OBJECTIVE: To ascertain the impact of advanced access and productivity-based pay
      on physician productivity and compensation, patient satisfaction, and medical
      group cost of delivering care. STUDY DESIGN: Longitudinal case study. METHODS:
      Study subjects were 105 primary care physicians (PCPs) continuously employed at a
      Minnesota medical group that implemented major changes in access to primary care
      appointments and to PCP compensation arrangements in 2000. We tracked physician
      productivity, physician compensation, patient satisfaction, and cost to the
      medical group per relative value unit (RVU) of patient care from 1998 through
      2002. RESULTS: In 1998, 105 PCPs (99.6 full-time equivalents [FTEs]) generated
      275,000 work RVUs (WRVUs), and PCP pay averaged 123,500 dollars per FTE. In 2002,
      the same 105 PCPs (now 98.1 FTEs) generated 374,000 WRVUs and 148,000 dollars pay
      per FTE. From 1998 through 2002, WRVUs per FTE rose 38%, PCP compensation
      increased 20%, cost of PCP compensation per WRVU produced fell by 13%, overall
      direct cost of running the clinics per total RVU fell by 20%, and patient
      satisfaction remained constant. Improvement in operating costs was due to
      increased physician productivity, lower physician compensation per RVU, and a
      decline in support staff per 10,000 RVUs from 6.80 to 4.50. CONCLUSIONS: It is
      possible to substantially and simultaneously improve costs of care, physician
      compensation, and patient access without harming patient satisfaction. Advanced
      access and productivity-based pay may be effective ways to address the challenges
      of timeliness, efficiency, and patient centeredness identified by the Institute
      of Medicine.

PMID- 17026412
TI  - Outpatient medication use and health outcomes in post-acute coronary syndrome
      patients.
AB  - OBJECTIVE: To investigate the pattern of postdischarge evidence-based outpatient
      medication use and its impact on subsequent hospital readmissions in post-acute
      coronary syndrome (ACS) patients. STUDY DESIGN: Prospective observational study.
      METHODS: A telephone survey was conducted to collect information from discharge
      to 8 months after discharge for 433 patients hospitalized with a primary
      diagnosis of ACS in 5 mid-Michigan hospitals. The survey data were then merged
      with chart review data from the initial hospitalization. We first conducted a
      longitudinal descriptive analysis of the utilization patterns of patient self
      reported medication use from discharge to the 8-month survey. Then, multivariable
      logit analysis was used to estimate the effect of post-ACS medication use on self
      reported hospital readmission at 3 months and 8 months after discharge.
      Propensity score matching was used to counter the possible bias induced by self
      selection of outpatient medication use. RESULTS: The pattern of outpatient
      medication use was dynamic. Most changes to medication regimens occurred within 3
      months after discharge, with fewer changes in the subsequent 5 months. Taking a
      beta-blocker, angiotensin-converting enzyme inhibitor, or angiotension receptor
      blocker significantly reduced the probability of hospital readmission 3 months
      after discharge. Propensity score matching produced similar statistically
      significant results. Re-hospitalization within 3 months after discharge was a
      strong predictor of later hospital readmission up to 8 months. CONCLUSION: Timely
      and appropriate medication adjustment in outpatient settings appears to be
      critically important to reduce hospital readmission among ACS patients.

PMID- 17026413
TI  - Low-density lipoprotein cholesterol goal attainment among high-risk patients:
      Does a combined intervention targeting patients and providers work?
AB  - BACKGROUND: Physicians are aware of the National Cholesterol Education Program
      guidelines; however, most patients fail to attain cholesterol goals. OBJECTIVE:
      To determine whether a combined program of patient education and provider
      awareness could improve the National Cholesterol Education Program goal
      attainment among patients at high risk for cardiovascular events. METHODS: One
      hundred seven high-risk patients with cardiovascular disease were educated in a
      single 15-minute session regarding their cholesterol levels, risk factors, and
      medication adherence. Those with scores of 2 or lower on the Morisky
      questionnaire were classified as low-adherence patients, and those with scores of
      3 or higher were classified as high-adherence patients. Seven physicians were
      provided this information and were requested to evaluate the dyslipidemia
      management of these patients. Lipid levels were reevaluated 8 to 12 weeks after
      the intervention. RESULTS: At the start of the study, 38 (35.5%) of the 107
      patients were at target low-density lipoprotein cholesterol (LDL-C) levels, and
      64 of the 107 patients (59.8%) were at target levels after the intervention. High
      adherence patients decreased their LDL-C levels from a mean of 118.6 mg/dL (3.07
      mmol/L) to 98.6 mg/dL (2.55 mmol/L); low-adherence patients increased their LDL-C
      levels after the intervention from 134.5 mg/dL (3.48 mmol/L) to 142.1 mg/dL (3.68
      mmol/L). A comparison between the LDL-C goal achievers vs nonachievers revealed a
      significant difference in adherence (P = .001). Among the goal achievers,
      significant decreases in preintervention vs postintervention total cholesterol
      levels (P = .001) and LDL-C levels (P = .001) were also noted. CONCLUSION: This
      study demonstrates that an intervention simultaneously targeting patients and
      providers is successful in improving goal attainment among high-risk patients.

PMID- 17026414
TI  - Implementation of evidence-based alcohol screening in the Veterans Health
      Administration.
AB  - BACKGROUND: Despite evidence-based guidelines, brief alcohol screening and
      counseling have not been routinely integrated into most primary care practices in
      the United States. OBJECTIVE: To describe the results of the implementation of
      evidence-based alcohol screening by the Veterans Health Administration (VA) in
      2004, as the first step toward implementation of brief alcohol counseling. STUDY
      DESIGN: This observational study of outpatients from all 21 VA networks relied on
      the following 2 data sources from the VA Office of Quality and Performance: (1)
      Medical record reviews, designed to compare VA networks quarterly, evaluated
      whether established VA patients had documented screening for alcohol misuse and
      documented follow-up assessment for alcohol use disorders among those who
      screened positive for alcohol misuse (January-March 2005); and (2) Mailed patient
      satisfaction surveys from 2004, which oversampled patients new to the VA
      (response rate, >70%), included the Alcohol Use Disorders Identification Test
      Consumption (AUDIT-C) questions and asked about past-year advice "to drink less
      or not to drink alcohol" from a VA provider. RESULTS: Based on 10 115 medical
      record reviews, 93% (range, 89%-96% across networks) of outpatients were screened
      for alcohol misuse, and 25% (range, 11%-36%) screened positive. Among screen
      positive patients, 42% (range, 5%-84%) had documented follow-up assessment, but
      absolute numbers of screen-positive patients evaluated were small (27-80 patients
      per network). Based on 235 481 patient surveys, the prevalence of alcohol misuse
      was 22% (range, 15%-27% across networks), and 28% (range, 20%- 36%) of screen
      positive patients reported receiving alcohol-related advice. Alcohol-related
      advice increased as AUDIT-C scores increased. CONCLUSION: The VA successfully
      implemented evidence-based alcohol screening, but the rate of follow-up among
      screen-positive patients remained low.

PMID- 17026416
TI  - A step therapy algorithm for the treatment and management of chronic depression.
AB  - Depression is a chronic and progressive condition that, when not treated
      adequately, can lead to severe morbidity and mortality in patients and increased
      costs for health plans. Despite the significance of this disease state, the
      majority of patients are not treated adequately to the widely accepted goal of
      remission. Patients who do not achieve remission are at greater risk of relapse
      and recurrence, more chronic depressive episodes, and a shorter duration between
      depressive episodes. Modeled partially after the Sequenced Treatment Algorithm to
      Relieve Depression (STAR*D) trial and based on trial data and the consensus
      statements of a panel of clinical professionals, a step therapy algorithm is
      proposed in this supplement, including considerations for screening and
      intervention. The primary concepts in the development of this algorithm were the
      use of the same clinical tool for both screening and diagnosis and the
      incorporation of frequent follow-up visits or calls to continuously monitor
      progress in patients being treated. Also discussed are considerations for drug
      therapy choices when switching is deemed necessary. Switching to a drug from a
      different class of agents than the failed trial drug is recommended based on the
      differential mechanism of action between classes.

PMID- 17026415
TI  - Association of income and prescription drug coverage with generic medication use
      among older adults with hypertension.
AB  - OBJECTIVE: To determine whether low-income seniors and those without prescription
      drug coverage are more likely to use generic cardiovascular drugs than more
      affluent and better insured adults. STUDY DESIGN: Cross-sectional analysis.
      METHODS: We used data from the 2001 Medicare Current Beneficiary Survey. Analyses
      included noninstitutionalized survey respondents over age 65 years with
      hypertension who used > or =1 multisource cardiovascular drugs (N = 1710). We
      examined the association of income and prescription coverage with use of generic
      versions of multisource drugs from 5 classes: angiotensin-converting enzyme (ACE)
      inhibitors, beta-adrenergic receptor antagonists (beta-blockers), calcium channel
      blockers, alpha1-adrenergic receptor antagonists (alpha-blockers), and thiazide
      diuretics. RESULTS: Rates of generic medication use were 88.5% (beta-blockers);
      92.8% (thiazides); 58.7% (calcium channel blockers); 60.7% (ACE inhibitors); and
      52.6% (alpha-blockers). In multivariate analysis of generic medication use
      aggregated across the 5 drug classes, individuals with incomes below 200% of the
      federal poverty level were modestly more likely to use generic medications
      compared with seniors with incomes above 300% of the poverty level. Seniors who
      lacked prescription coverage were more likely to use generics than those who had
      employer-sponsored coverage, although the association was of marginal statistical
      significance (relative risk = 1.29, 95% confidence interval = 1.00, 1.60).
      CONCLUSION: Seniors with low incomes or no prescription coverage were only
      somewhat more likely to use generic cardiovascular drugs than more affluent and
      insured seniors. These findings suggest that physicians and policy makers may be
      missing opportunities to reduce costs for Medicare and its economically
      disadvantaged beneficiaries.

PMID- 17026420
TI  - The practice and politics of Indigenous health nursing.

PMID- 17026421
TI  - Indigenous health care: advances in nursing practice.

PMID- 17026422
TI  - Critical cultural perspectives and health care involving Aboriginal peoples.
AB  - Despite a growing body of critical scholarship in nursing, the concept of culture
      continues to be applied in ways that diminish the significance of power relations
      and structural constraints on health and health care. In this paper, we take a
      critical look at how assumptions and ideas underpinning conceptualizations of
      culture and cultural sensitivity can influence nurses' perceptions of Aboriginal
      peoples and Aboriginal health. Drawing on examples from our research, we examine
      how popularized assumptions about culture can shape nurses' views of Aboriginal
      patients. These assumptions and perceptions require closer scrutiny because of
      their potential to influence nurses' practice with Aboriginal patients. Our
      specific aims are to: (a) consider some of the limitations of cultural
      sensitivity in relation to health care involving Aboriginal peoples; (b) explore
      how ideas about culture have the potential to become problematic in nursing
      practice with Aboriginal peoples; and (c) explore the relevance of a 'critical
      cultural approach' in extending our understanding of culture in relation to
      Aboriginal peoples' health. We discuss a critical cultural perspective as one way
      of broadening nurses' understandings about the complexities of culture and the
      many facets of culture that require critical consideration. In relation to
      Aboriginal health, this will require nurses to develop greater critical awareness
      of culture as a relational process, and as necessarily influenced by issues of
      racism, colonialism, historical circumstances, and the current political climate
      in which we live.

PMID- 17026423
TI  - Issues of language across the cultural [and colonial] divide.

PMID- 17026424
TI  - It's only a mistake if you make it twice.

PMID- 17026425
TI  - Decolonisation: a critical step for improving Aboriginal health.
AB  - Aboriginal health continues to be in crisis in Australia although expenditure has
      increased in service provision, strategic planning, research and policy
      development over the last thirty years. This paper recommends that a shift must
      occur to make Aboriginal health improvement a reality. This shift requires the
      decolonising of Aboriginal health so that the experts in Aboriginal health,
      namely Aboriginal people, can voice and action initiatives that address their
      health issues. This shift is from the current western dominant approach that
      continues to manage Aboriginal health in its linear spectrum of illness and
      disease. Aboriginal people view health differently; their contexts for health
      issues are also diverse requiring a more holistic and informed response.

PMID- 17026426
TI  - Amorphous practice: nursing in a remote Indigenous community of Australia.
AB  - Nurses are key providers of health care in remote Indigenous communities
      throughout Australia. Evidence of nurses' actual practice and the outcomes of
      their care for clients in this context, however, is lacking. This exploratory
      research describes how nursing is practised in a remote Aboriginal community and
      reveals many anomalies. The overall theme, termed amorphous practice, defines the
      changeable character of practice from nurse to nurse and from situation to
      situation. The themes underlying amorphous practice are termed detachment,
      diffusion, and beyond the nursing domain. Each theme is described by way of its
      characteristics, the strategies nurses use to deal with the situation, and the
      consequences. The significance of these findings raise concerns for the
      accountability of nursing and most of all for the rights of Indigenous people in
      remote areas to basic standards of safe health care.

PMID- 17026427
TI  - Characterising Maori nursing practice.
AB  - This paper summarises research which addresses the question What might constitute
      Maori nursing practice? The research design adopted was influenced by Kaupapa
      Maori methodology and used a semi-structured, qualitative, in-depth interview
      process. It was found that by understanding the current experiences of Maori
      registered nurses, their reflections on their preparation for practice, and their
      current practice, we are able to identify the present and future training and
      practice needs of Maori nurses. Maori nursing practice can be characterised as
      having five features: the promotion of cultural affirmation including cultural
      awareness and identity; the support of, and access to Maori networks; the
      adoption of Maori models of health; the enabling of visibility and pro-activity
      as Maori nurses; and, the validation of Maori nurses as effective health
      professionals. Three recommendations for promoting Maori nursing practice are
      made in relation to staff in the workplace and in nurse education programmes. All
      nursing staff need to be alert to: 1. The impact of western scientific models on
      Maori healthcare; 2. The (often passive) non-acceptance of Maori within
      mainstream institutions; and 3. The benefits of valuing Indigenous nursing
      programmes.

PMID- 17026428
TI  - Indigenous values, cultural safety and improving health care: the case of Native
      Hawaiians.

PMID- 17026429
TI  - Assessing pain across the cultural gap: Central Australian Indigenous peoples'
      pain assessment.
AB  - Pain is a dynamic, unpleasant sensory experience with many physical,
      psychological, and social implications. Assessment of pain within a bicultural
      environment has the potential to cause ineffective pain management and
      unnecessary suffering amongst Indigenous people. It has been recognised that non
      Indigenous nurses sometimes demonstrate culturally unsafe practices during the
      pain assessment process. These practices have arisen due to limited knowledge of
      what constitutes 'cultural safety' and how nurses can apply this concept during
      pain assessment. Culturally safe pain assessment strategies have been developed
      based upon research findings and through consultation with Indigenous people.

PMID- 17026430
TI  - At what cost to health? Tlicho women's medical travel for childbirth.
AB  - Medical travel policies are instituted in all rural and remote areas of Canada as
      a means of providing universal health care services to residents. These policies
      are framed, developed and implemented from a colonial perspective and require re
      examination through a more inclusive and collaborative postcolonial lens. The
      purpose of this paper is to discuss the medical travel policy for childbirth in
      Canada's Northwest Territories from a postcolonial perspective and in
      consideration of the cultural safety of pregnant Tlicho women. The context within
      which Tlicho birthing and this policy thrives is reviewed along with the
      exploration of future possibilities. Personal, socioeconomic, political and legal
      factors surrounding birthing are highlighted. It is anticipated, that by
      illuminating the oppressive and paternalistic nature of this childbirth policy,
      there will be heightened awareness that fosters transitions within the system to
      transform current risk discourse creating new possibilities for Tlicho women in
      the birth of their babies.

PMID- 17026431
TI  - Insights on Aboriginal peoples' views of cancer in Australia.
AB  - Although the incidence of cancer in Indigenous peoples is similar to its
      incidence in the overall Australian population, Indigenous peoples are less
      likely to access early detection and medical interventions resulting in higher
      mortality and morbidity rates. To explore and address this discrepancy, the
      National Health and Medical Research Council funded a research study to examine
      Indigenous peoples' views of cancer and cancer treatments with an end goal of
      developing an innovative model of Indigenous Palliative Care. Seventy-two
      participants were interviewed from four geographical areas within the Northern
      Territory (Australia) including patients, caregivers, Indigenous and non
      Indigenous health care workers, and interpreters. Indigenous peoples' views of
      cancer have to be examined within a historical, socio-political, and cultural
      context. There is no Indigenous word for cancer and the Western biomedical
      language that semantically constructs the notion of cancer is not widely
      understood. Additionally, for many Indigenous people, the aetiology of cancer is
      embedded in beliefs about the spiritual world of curses and payback from
      perceived misdeeds. The paper advocates for cross-cultural education initiatives,
      stressing the importance of a two way education strategy incorporating a process
      whereby medical and nursing personnel would improve their understanding of
      Indigenous peoples' view of cancer and Indigenous peoples would learn more about
      prevention and treatment of cancer from a biomedical perspective.

PMID- 17026432
TI  - The experience of whanau caring for members disabled from the effects of a
      cerebro-vascular accident.
AB  - The study sought to understand the experience of Maori in accepting
      responsibility for the care of a whanau member following a cerebro-vascular
      accident (CVA). The importance and role of whanau, kaumatua and kuia to Maori as
      a distinctive ethnic entity is well known and acknowledged in coming to an
      understanding of Maori society. Whanau has a very large part to play in the care
      of the family member disabled by CVA. There is extensive literature that deals
      with these issues, yet there is little that deals with disability issues and in
      particular those issues that arise following CVA. A qualitative study was
      conducted examining the experience of Whanau caring for members disabled from the
      effects of CVA. Individual and focus group interviews were undertaken with Maori
      patients and their caregivers to explore this phenomenon. Data were analysed
      using a thematic analysis approach and highlighted three time stages of concern,
      namely (1) the onset of the event, (2) hospitalisation, and (3) discharge care.

PMID- 17026433
TI  - Nursing partnerships in Indigenous health.

PMID- 17026434
TI  - Relationship building for research: the Southern Saskatchewan/Urban Aboriginal
      Health Coalition.
AB  - The Southern Saskatchewan/Urban Aboriginal Health Coalition is an
      interdisciplinary, intersectoral team of researchers and communities dedicated to
      exploring what 'culturally respectful' care means in Aboriginal communities.
      Although the purpose of the research project was to examine this concept in an
      effort to improve health care service delivery and education for health
      professions, the members of the Coalition realized early in the process that one
      of the primary factors related to the success of the project would be the
      building and sustaining of relationships. This paper describes a relational
      process that was used to initiate, facilitate, and support a research partnership
      with the Aboriginal communities. Through a community-based process, two
      communities and the Coalition used sharing circles and workshops as a method to
      create relationships and begin a discussion about what constitutes key elements
      of culturally respectful health care and education. These elements have not yet
      been determined as the Coalition and community members have focused on fostering
      relationships which have been critical to building the partnership with the
      Aboriginal communities.

PMID- 17026435
TI  - A nursing partnership for better outcomes in Aboriginal mental health, including
      substance use.
AB  - This article draws on our participatory action research findings and
      interventions, such as advocacy and professional education, as applied during and
      after a large project focusing on Aboriginal mental health and safe medication
      management. The project was conducted by our research team and partners,
      community-controlled Aboriginal health services, and community leaders. The paper
      provides a discussion of major Aboriginal mental health issues gleaned from the
      literature, along with a discussion, and a conceptual model for conducting
      ethical Aboriginal health research, that has both evolved and guided us. It is
      hoped that this paper will assist nurses and other professional colleagues to
      work more effectively with Aboriginal peoples.

PMID- 17026436
TI  - Meeting the health needs of Indigenous people: how is nursing education meeting
      the challenge?
AB  - Australian Indigenous people continue to have health outcomes that are near to
      the worst in the world but similar to those of the Indigenous peoples in
      countries such as Canada and New Zealand. Numerous policies and strategies have
      been implemented in Australia in an attempt to rectify this situation. This paper
      provides an overview of the issues directly related to the provision of a skilled
      workforce prepared for delivery of appropriate health services to Indigenous
      people. It includes an overview of the need for Indigenous people in nursing and
      the issues facing them when they enrol in undergraduate nursing courses. It also
      proposes changes necessary to ensure non-indigenous nurses are better prepared to
      work effectively with Indigenous people in the future.

PMID- 17026437
TI  - The Yapunyah project: embedding Aboriginal and Torres Strait Islander
      perspectives in the nursing curriculum.
AB  - The Yapunyah Project is an initiative of the Faculty of Health at Queensland
      University of Technology. It was instigated to further improve the development of
      cultural competence in health graduates with respect to Aboriginal and Torres
      Strait Islander perspectives. The project was informed by the cultural competence
      in healthcare delivery models of Campinha-Bacote (1998a) and Cross, Bazron,
      Dennis and Isaacs (1989) and by the cultural safety reforms to nursing curricula
      in New Zealand. The Yapunyah Project involved extensive consultation and
      collaboration with Indigenous staff and health experts in the local Aboriginal
      and Torres Strait Islander community. A core curriculum, and associated graduate
      transcultural competencies, were informed by these discussions and earlier
      reforms in health curricula by the Committee of Deans of Australian Medical
      Schools and the Royal Australian College of General Practitioners. Although the
      overall project involved four separate schools within the faculty, this paper
      details the experience of embedding Indigenous perspectives within the
      undergraduate nursing curriculum. The experience has been a challenging and
      positive one, and the reforms have been supported by a sustainable framework.
      This paper outlines how one university faculty is endeavouring to educationally
      prepare nursing students to practice with evidence-based transcultural nursing
      knowledge based on culture care values, beliefs, and traditional lifeways of
      Indigenous people of Australia. As such, the project aims to contribute to the
      improvement and promotion of the health and well-being of Indigenous Australians
      in culturally and ethnohistorically meaningful ways.

PMID- 17026439
TI  - Nursing, Indigenous peoples and cultural safety: so what? Now what?

PMID- 17026438
TI  - Is it Aboriginal friendly? Searching for ways of working in research and practice
      that support Aboriginal women.
AB  - This article describes my journey as a nurse as I search for better ways to work
      with urban Aboriginal women. Learning as I build and maintain trusting
      relationships with Elders, Aboriginal health professionals and communities has
      been an important first step. Incorporating reflective practice, participatory
      action research and ethical guidelines has further assisted me to work in more
      culturally safe and respectful ways. While there has been increasing recognition
      of access and equity issues in Australia's current neo-colonial period, actual
      improvements have been very slow to emerge. Meanwhile many Aboriginal people
      continue to experience poor levels of health. My hope is that this article can
      contribute to the growing body of knowledge that recognises the impact of past
      and present colonisation practices and shifts health care towards collaborative
      healing and well being models that are more supportive of Aboriginal people and
      their needs. The emphasis on Aboriginal women's health rather than mixed gender
      health care comes from my experiences in sexual health, where many Australian
      Aboriginal women prefer to access 'women only' services.

PMID- 17026448
TI  - Postoperative chemotherapy in non-small cell lung cancer: still more questions
      than answers.

PMID- 17026449
TI  - Gene therapy breakthrough in cancer treatment.

PMID- 17026450
TI  - Thalidomide in multiple myeloma: past, present and future.
AB  - Thalidomide was introduced in the treatment of multiple myeloma in the late
      1990s. Following the initial results, which demonstrated dramatic response rates
      in heavily pretreated patients, a number of Phase II studies have confirmed the
      efficacy of this agent in relapsed patients. However, a high incidence of side
      effects at the dosage initially recommended (400 mg/day) justified further
      studies with lower doses of thalidomide given alone or in combination with
      dexamethasone or chemotherapy. Thalidomide is currently considered as one of the
      most active agents in relapsed myeloma. Recent studies have demonstrated that
      thalidomide could also be used as part of frontline therapy. The combination of
      thalidomide plus dexamethasone as initial therapy appears to be slightly superior
      to dexamethasone alone or to vincristine-doxorubicine-dexamethasone, but with an
      increased risk of deep vein thrombosis. Maintenance with thalidomide after
      autologous transplantation appears to increase the complete remission rate and to
      prolong progression-free survival. The combination of thalidomide plus melphalan
      and prednisone is superior to the classical melphalan-prednisone regimen in
      elderly patients, and will become the standard of care. Thalidomide has been
      registered in the USA in combination with dexamethasone in newly diagnosed
      patients, but is not yet registered in the European Union. Its use is currently
      challenged by bortezomib and by thalidomide's analog lenalidomide.

PMID- 17026451
TI  - Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
      deterioration in quality of life. The emetogenicity of the chemotherapeutic
      agents, repeated chemotherapy cycles and patient risk factors (female gender,
      younger age, alcohol consumption, history of motion sickness) are the major risk
      factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists
      plus dexamethasone has significantly improved the control of acute CINV, but
      delayed nausea and vomiting remains a clinical problem. A new agent,
      palonosetron, has recently been approved for the prevention of acute CINV in
      patients receiving either moderately or highly emetogenic chemotherapy and for
      the prevention of delayed CINV in patients receiving moderately emetogenic
      chemotherapy. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life
      and a higher binding affinity than first-generation 5-HT3 receptor antagonists.
      In a single dosing study, palonosetron was highly effective in controlling CINV
      compared with a single dose of dolasetron or ondansetron in patients receiving
      moderately emetogenic chemotherapy. Palonosetron in combination with
      dexamethasone demonstrated control of CINV in patients receiving highly
      emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent
      courses of chemotherapy compared with the initial course of chemotherapy. There
      were no clinically relevant differences seen among palonosetron, ondansetron or
      dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse
      reactions reported in the clinical trials were the most common reactions reported
      for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based
      anti-emetic combinations in moderately and highly emetogenic chemotherapy, as
      well as in the clinical setting of multiple-day chemotherapy, have been reported.
      Future studies may consider the use of palonosetron with current and other new
      agents and in other clinical settings, such as bone marrow transplantation and
      radiation therapy.

PMID- 17026452
TI  - Docetaxel in the treatment of gastric cancer.
AB  - Docetaxel is part of the standard chemotherapy in breast, non-small cell lung
      cancer and androgen-independent metastatic prostate cancer and has recently been
      approved for advanced gastric cancer. It demonstrated promising single-agent
      efficacy in gastric cancer and was therefore investigated in different
      combination regimens. The combination of docetaxel with 5-fluorouracil (5-FU),
      capecitabine, irinotecan or cisplatin demonstrated high efficacy. The triple
      combination of docetaxel/cisplatin and 5-FU (DCF) was investigated in randomized
      Phase II trials and a randomized Phase III study (TAX325). In TAX325, DCF
      demonstrated superiority in terms of time to tumor progression, response rate and
      survival against a cisplatin/5-FU combination. Docetaxel was therefore approved
      for advanced gastric cancer by the US FDA and the European Agency for the
      Evaluation of Medicinal Products and will evolve as an integral part of routine
      combination regimens against gastric cancer. This review will discuss and
      interpret the different Phase II and III trials of docetaxel in gastric cancer.

PMID- 17026453
TI  - Is axillary clearance the standard of care for breast cancer patients with
      sentinel node involvement?
AB  - Sentinel node biopsy (SNB) has become accepted for staging the axilla in early
      breast cancer with avoidance of axillary lymph node dissection (ALND) in patients
      with negative SNB. For those with positive SNB, the standard surgical management
      is ALND; however, this approach is increasingly being challenged. The central
      problem is that it is not possible to preoperatively predict whether the SNB will
      be positive, and it is even more difficult to determine the likelihood of
      nonsentinel node positivity. Various histopathological features indicate
      increased risk of nonsentinel node metastasis, including size of SNB metastasis,
      presence of lymphovascular invasion, multifocality, number of involved sentinel
      nodes and, conversely, the number of negative sentinel nodes. These features have
      been combined to produce predictive nomograms but, understandably, these still
      lack precision. Presently, the decision to avoid ALND will depend upon both the
      clinician and the patient's impression of risk, but if either requires assurance
      that no residual axillary disease remains, a completion clearance will be
      required.

PMID- 17026454
TI  - Tumor dormancy and the role of metastasis suppressor genes in regulating ectopic
      growth.
AB  - Metastasis, or tumor growth in an ectopic site, may occur several years after
      apparently successful treatment of the primary malignancy. Clinical dormancy is
      seen in a large number of cancer patients, but once growth in an ectopic site
      initiates, current adjuvant therapies are inadequate and the majority of patients
      with metastatic disease will die. Many genes may regulate ectopic growth in a
      secondary site, including a small subset, termed the metastasis suppressor genes.
      Investigation into this class of genes holds promise in terms of gaining a
      greater understanding of tumor dormancy and how the process of metastasis may be
      naturally inhibited. This review will focus on the role of metastasis suppressor
      genes in tumor dormancy. Insights into the metastatic process from studies of
      metastasis suppressor genes may lead to novel targets for antimetastatic therapy
      through drug-induced reactivation of one or more of these genes and/or their
      respective signaling pathways.

PMID- 17026455
TI  - Recent advances in the systemic management of colorectal cancer.
AB  - Colorectal cancer represents one of the most prevalent malignancies. There have
      been considerable improvements in the management of the disease in the last
      decade, including advances in surgery. In terms of systemic management, 5
      fluorouracil, usually with leucovorin, has remained the mainstay of chemotherapy
      for colorectal cancer in both the adjuvant and metastatic settings. In the late
      1990s, irinotecan and oxaliplatin reached the clinical arena, and the
      introduction of these agents has led to significant improvements in outcomes.
      More recently, several biopharmaceuticals, including the monoclonal antibodies
      bevacuzimab and cetuximab, have shown promise in clinical studies. These novel
      agents are now being incorporated into treatment schedules for colorectal cancer.
      This review assesses recent improvements in the systemic management of large
      bowel cancer and highlights future challenges.

PMID- 17026456
TI  - CXC chemokines and prostate cancer: growth regulators and potential biomarkers.
AB  - CXC chemokines are a subset of chemotactic cytokines that possess angiogenic or
      angiostatic properties. Using genetically engineered mice lacking the receptors
      for these ligands, recent research has demonstrated a significant role for CXC
      chemokines in the development and growth of prostate tumors. The Duffy
      antigen/receptor for chemokines (DARC), which only binds to CXC chemokines that
      have angiogenic properties, is a nonsignaling receptor expressed on erythrocytes
      that appears to function by clearing these chemokines from sites of
      overproduction. The majority of men of African descent lack this receptor on
      their erythrocytes, suggesting that loss of this receptor may contribute to
      aggressive tumor phenotypes in these individuals. Thus, CXC chemokines and the
      erythrocyte DARC may serve as important growth regulators and biomarkers for
      prostate cancer stage and progression.

PMID- 17026457
TI  - Novel approaches for the management of patients with Ewing sarcoma.
AB  - The concepts of tailored therapy according to genetic profiling and response
      based on minimal residual disease evaluation during therapy are attracting
      increasing interest in modern clinical oncology. Children with acute
      lymphoblastic leukemia are being stratified to various treatment arms with
      different intensities according to the genetic characteristics of their leukemia
      and their response to therapy as measured by real-time polymerase chain reaction.
      Our ability to quickly identify patients with Ewing sarcoma who have a poor
      prognosis, and to offer them aggressive therapeutic modalities, such as stem cell
      transplantation, may result in an improved cure rate. Based on the knowledge
      gained by gene expression profiling and gene silencing techniques we can expect
      the emergence of new specific drugs that will target malignant cells without
      causing damage to normal tissue, resulting in improved cancer therapy.

PMID- 17026458
TI  - Role of surgery in the management of soft tissue tumors.
AB  - Pediatric soft tissue sarcomas (STSs), of which rhabdomyosarcoma is the most
      common, constitute approximately 5-6% of all cancers in children. Biopsy, being
      incisional or rarely excisional, is an essential primary diagnostic step, while
      in some cases it may be followed by primary re-excision to establish a correct
      diagnosis in which molecular analysis can be helpful. Most European STS treatment
      groups favor preoperative chemotherapy, sometimes combined with preoperative
      irradiation. Local therapy is essential, in which surgery remains an important
      adjunct. However, it has to be applied in a multidisciplinary, combined fashion
      in close cooperation with oncologists, pathologists and radiotherapeutists.
      Current 5-year survival in rhabdomyosarcoma reaches 60-70% in nonmetastatic cases
      and remains below 20% in metastatic situations. Outcome in pediatric
      nonrhabdomyosarcoma STS is similar.

PMID- 17026459
TI  - New drugs for the treatment of metastatic or refractory soft tissue sarcomas in
      children.
AB  - Children with relapsed, recurrent or metastatic sarcomas represent a therapeutic
      challenge for the pediatric oncologist. Strategies for the development of newer
      therapies for children with these sarcomas have, in the past, been histology
      specific. For example, drug development in rhabdomyosarcoma has relied upon the
      preclinical xenograft model, whereas therapies for pediatric
      nonrhabdomyosarcomatous soft tissue sarcomas have mostly been derived from adult
      trials. The progress to date and the tools used in the treatment of advanced
      pediatric sarcomas will be summarized in this review.

PMID- 17026460
TI  - In memoriam: Serafino Zappacosta (1935-2006).

PMID- 17026461
TI  - Antigen mimicry, epitope spreading and the pathogenesis of pemphigus.
AB  - The molecular and cellular pathogenesis of pemphigus remains unclear. However,
      the integrity of intraepidermal and dermoepidermal adhesion appears to be of
      special importance, and the presence of antibodies directed against desmosomal
      plaque proteins can provoke pemphigus-like pathologies. Antibodies reactive with
      various tissue antigens have been detected in pemphigus-like skin conditions. Two
      major factors determining the occurrence of different pemphigus subforms are
      antigen mimicry and epitope spreading, as these two phenomena underpin antibody
      generation in response to different antigens. This multiplicity of target
      antigens and antibody responses may lead to diagnostic problems early in the
      disease and may also explain the apparent transformation of one disease subform
      into another as time progresses.

PMID- 17026462
TI  - Human leukocyte antigen class I and MICA haplotypes in a multicase family with
      Cladophialophora carrionii chromoblastomycosis.
AB  - Previous studies carried out in an endemic semiarid region northwest of Venezuela
      at Falcon State have shown a prevalence of 15.4/1000 of chromoblastomycosis
      following traumatisms with xenophile vegetation infected with Cladophialophora
      carrionii. We performed high-resolution DNA typing of human leukocyte antigen
      (HLA)-A, -B and -C and major histocompatibility complex class I chain related
      gene A (MICA) alleles and segregation analysis in 49 members of one extended
      family with 12 affected individuals, who have lived for approximately 70 years in
      this endemic zone. None of the alleles, haplotypes or genotypes is shared by all
      the patients. No deviation from the expected HLA haplotype distribution or
      association of chromoblastomycosis with HLA-A, -B and -C haplotypes was observed.
      Further, a haplotype-sharing transmission/disequilibria testing of 11 nuclear
      families did not give enough evidence to claim linkage (P = 0.398), suggesting
      that genes located in the short arm of chromosome 6 may not be relevant in the
      immune response toward infection with C. carrionii in this Venezuelan endemic
      zone. Deleted MICA alleles on HLA-B*4802 haplotypes were present among several
      members of the extended family, but only two of them were affected.

PMID- 17026463
TI  - Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis:
      association with HLA-DR alleles.
AB  - Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a
      consequence of an exaggerated immune response to group A beta-haemolytic
      streptococci, which causes pharyngitis. Major manifestations of ARF include
      carditis, arthritis and chorea. Several investigators have attempted to establish
      a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in
      various studies has been found, although associations with certain antigens were
      reported. The aim of this study was to analyse whether HLA-DR alleles play a role
      in the resistance or susceptibility to streptococci-related disorders including
      rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal
      pharyngitis in Turkish patients. The study included 102 patients with RHD, 71
      persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR
      alleles were typed by using polymerase chain reaction (PCR)-sequence-specific
      primers. Positive association with HLA-DRB1*07 allele was found for RHD when
      compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01,
      odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for
      recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P <
      0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was
      decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01,
      OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic
      factor in increasing the susceptibility to develop RHD and recurrent
      streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor
      against RHD.

PMID- 17026464
TI  - Class II HLA allele polymorphism: DRB1, DQB1 and DPB1 alleles and haplotypes in
      the New Zealand Maori population.
AB  - Class II alleles of interest to transplantation comprise the DRB1, DQB1 and DPB1
      loci. Sequence-based typing was used to determine the class II allelic
      variability present in New Zealand Maori, a population with close genetic ties to
      Polynesia and known anthropological and linguistic connections to mainland Asia.
      The most common DRB1 alleles identified were DRB1*1201, DRB1*110101, DRB1*0403
      and DRB1*080302, with frequencies of 21.5%, 14%, 11.25% and 9.25%, respectively.
      Standard linkages between the DRB1 locus and the DRB3, 4 and 5 loci were
      maintained, with no novel patterns identified. The most common DQB1 alleles
      identified were DQB1*030101, DQB1*060101, DQB1*020101, DQB1*0602 and DQB1*050201,
      with frequencies of 29.5%, 8%, 7.8%, 6.4% and 6.2%, respectively. The most common
      DPB1 alleles identified were DPB1*0501, DPB1*040101 and DPB1*020102, with
      frequencies of 40.2%, 28.89% and 15.83%, respectively. A total of 80 estimated
      DRB1-DQB1 two-locus haplotypes were detected. DRB1*1201-DQB1*030101 was the most
      frequent (15.40%) haplotype, followed by DRB1*110101-DQB1*030101 (9.97%),
      DRB1*0403-DQB1*030201 (7.37%) and DRB1*080302-DQB1*060101 (5.96%). The allelic
      variation determined is being used in further analysis of the requirement for
      bone marrow transplantation in the New Zealand Maori population and has
      implications for optimal ethnic donor distribution on the New Zealand Bone Marrow
      Donor Registry, anthropological studies and disease association.

PMID- 17026465
TI  - Analysis of the expression of HLA class I, proinflammatory cytokines and
      chemokines in primary tumors from patients with localized and metastatic renal
      cell carcinoma.
AB  - Changes in the human leukocyte antigen (HLA) class I expression and cytokine and
      chemokine production both by cancer cells and by normal surrounding tissue are
      believed to be responsible for immune escape and tumor progression. In this
      study, we compared the tumor expression levels of HLA heavy chain (HLAhc), beta-2
      microglobulin (beta2m), chemokines (Interferon-gamma-inducible Protein-10 (IP
      10), Interferon-inducible T-cell Alpha-Chemoattractant (I-TAC), Stromal cell
      Derived Factor-1 (SDF-1), Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha)
      and Regulated upon Activation, Normally T-Expressed, and presumably Secreted
      (RANTES)) and cytokines (Vascular Endothelial Growth Factor (VEGF), Interferon
      gamma (IFN-gamma), Interleukin-10 (IL-10), Tumor Growth Factor-beta (TGB-beta))
      in primary tumors and adjacent normal tissues from patients with localized and
      metastatic renal cell carcinoma (RCC) using a quantitative real-time polymerase
      chain reaction technique. We report that the expression of HLAhc, beta2m and the
      studied cytokines and chemokines (except for SDF-1) was significantly higher in
      the tumor (29 samples) than in the normal tissue (14 samples). When we compared
      the tumor expression levels between patients with localized RCC and patients with
      advanced metastatic stage, we found that the messenger RNA expression levels of
      HLAhc and beta2m were much lower in patients with metastatic RCC (6 cases) than
      in patients with localized cancer (23 cases), with levels similar to those in
      normal tissue. This was also confirmed on a protein level by immunohistological
      labeling of tumor tissues. Thirty-nine percent of the analyzed RCC tumors showed
      partial loss of HLA class I molecules, while 6% of the tumors showed HLA class I
      total loss. The expression of IP-10, SDF-1 and VEGF-c was also significantly
      lower in patients with advanced tumor, while the IFN-gamma expression in
      metastatic RCC was not detectable. Our findings show that primary RCC tumors are
      characterized by a high expression of HLAhc and a presence of proinflammatory
      mediators and chemokines. We also observed that disease progression and
      development of metastasis in RCC are associated with decreased expression of
      HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This microenvironment may suppress the
      cytotoxic response, creating conditions that favor tumor escape and cancer
      progression.

PMID- 17026466
TI  - Maternal human leukocyte antigen-G polymorphism is not associated with pre
      eclampsia in a Chinese Han population.
AB  - Pre-eclampsia is a multisystem disorder of pregnancy and remains the leading
      cause of both maternal and fetal morbidity and mortality in many countries.
      Despite extensive studies, the underlying mechanisms still remain unknown.
      Besides its restricted expression in the tissues of placenta and its function in
      regulating immune suppression and in ensuring successful invasion of placental
      tissues into maternal deciduas, it has been postulated that HLA-G may play a role
      in modulation of immune tolerance at the fetal-maternal interface. Aberrant HLA-G
      expression may result in pregnancy disorders that are associated with poor
      invasion of extravillous cytotrophoblast into maternal spiral arteries, such as
      pre-eclampsia. Studies have shown that pre-eclampsia is largely under genetic
      control, but genetic mechanisms underlying the disorder have yet to be
      determined. In the current study, we focus on the potential role of HLA-G
      polymorphism in the pathogenesis of pre-eclampsia. Samples were obtained from
      Chinese Han primiparous women with pre-eclampsia and irrelative normal women, and
      case-matched placentas were genotyped for the HLA-G polymorphism in the exons 2,
      3, and 4, and the 14-base-pair (bp) insertion/deletion polymorphism in the 3'
      untranslated region of exon 8 was analyzed separately. The frequency of HLA-G
      polymorphism in these samples was not significantly different from those of
      normal controls, indicating that maternal HLA-G polymorphism is not associated
      with the risk for pre-eclampsia in this Chinese Han population. However, the
      maternal 14-bp insertion/deletion polymorphism is ethnically different.

PMID- 17026467
TI  - Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca
      mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem
      cell antigen.
AB  - Human prominin-1 (CD133 or AC133) is an important cell surface marker used to
      isolate primitive hematopoietic stem cells. The commercially available antibody
      to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated,
      cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene
      and determined its coding potential. Following the nomenclature of prominin
      family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid
      sequence data of the putative rhesus prominin-1.s1 could be used in designing
      antigenic peptides to raise antibodies for use in isolation of pure populations
      of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there
      has been no previously published report about the isolation of a prominin-1 cDNA
      from rhesus monkey (Macaca mulatta).

PMID- 17026468
TI  - IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis.
AB  - Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection,
      unresolving inflammation and progressive lung damage. Bronchiectasis can be
      associated with autoimmune diseases including ulcerative colitis. Defects of both
      innate and adaptive immunity have been proposed. The airway inflammation is
      characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils
      and T cells. Here we investigated two candidate gene polymorphisms that may
      contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that
      is implicated in IL-8 binding and neutrophil trafficking as well as the
      interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of
      IFNgamma production. These polymorphisms were distributed similarly in the
      idiopathic bronchiectasis group and controls, suggesting that these two candidate
      gene polymorphisms are not associated with disease susceptibility.

PMID- 17026469
TI  - Association of interleukin-1 receptor antagonist gene polymorphism and
      susceptibility to human brucellosis.
AB  - The aim of this study was to determine the influence of the polymorphism within
      the intron 2 of the interleukin-1 receptor antagonist gene (IL-1Ra) on the
      susceptibility to or development of brucellosis. A total of 255 patients with
      brucellosis and 162 healthy volunteers were genotyped for polymorphisms in intron
      2 of the IL-1Ra gene. The frequency of allele 2 of the IL-1Ra gene was
      significantly higher in patients with brucellosis compared with the controls
      (24.5% vs 18.5%, P = 0.03). Although the heterozygosity was more prevalent in
      patients than in control individuals, it did not have any statistical
      significance (P = 0.1). Alleles 3, 4, and 5 were absent in our study population.
      This work is the first that verifies a significant association between genetic
      polymorphism of IL-1Ra and susceptibility to brucellosis.

PMID- 17026470
TI  - Analysis of the C/T(-1) single nucleotide polymorphism in the CD40 gene in
      multiple sclerosis.
AB  - The costimulatory CD40-CD40L pathway plays a critical role in the generation and
      maintenance of adaptive immune responses. Genetic interference of CD40-CD40L
      interactions strongly influences the onset and course in many autoimmune disease
      models including experimental autoimmune encephalomyelitis. We analysed the
      association of a single nucleotide polymorphism of the CD40 gene (C/T(-1)) in 287
      patients with multiple sclerosis (MS) and 184 matched controls. No significant
      differences were found in the frequency of the C/T(-1) polymorphism between the
      patients with MS and the controls (53% vs 49%) or among different MS subtypes.
      Cell surface expression of CD40 did not differ within the different genotypes,
      but carriers of the T allele showed a trend for a lower stimulatory index
      compared with individuals with the CC genotype. Although these subtle differences
      indicate functional consequences in the immune stimulatory capabilities related
      to the CD40 C/T(-1) polymorphism, our population-based study found no association
      with disease susceptibility or disease course in MS.

PMID- 17026471
TI  - Characterization of HLA-B*5516, -B*1313, -B*9512, and -DRB1*1457 alleles
      identified in a southwest Chinese population.
AB  - The human leukocyte antigen (HLA)-B*5516 allele differs from the B*5502 by a
      single 97 T --> C substitution (His to Tyr at position 33) in exon 2. The B*1313
      allele results from 419 T --> A and 420 A --> C substitutions, encoding a Leu to
      Tyr substitution at 140 in exon 2 of the B*1301 allele. The B*9512 allele differs
      from B*1502 by a single 360 G --> C substitution (Gln to His at 120) in exon 3.
      The DRB1*1457 allele appears to be a hybrid molecule generated by recombination
      between the DRB1*13 and DRB1*14 alleles. The serological equivalents of these new
      alleles are HLA-B22, -B13, -B15, and DR13, respectively. Family studies detected
      two rare haplotypes: A*11, B*9512, DRB1*14 and A*24, B*52, Cw*07, DRB1*1457,
      DRB3*020201, DQB1*050301. The gene frequencies of these alleles in the Chinese
      population are less than 0.0001.

PMID- 17026472
TI  - The new human leukocyte antigen-A*2631 is characterized by a new HLA-A
      polymorphism at amino acid position 62.

PMID- 17026473
TI  - A novel HLA-B*44 allele, B*4446, identified by sequence-based typing in a Chinese
      donor.

PMID- 17026474
TI  - Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1460.

PMID- 17026475
TI  - Exon 2 sequence analysis of a novel HLA-DRB1 allele, DRB1*1520.

PMID- 17026478
TI  - Effect of pro-inflammatory stimuli on mucin expression and inhibition by
      secretory leucoprotease inhibitor.
AB  - Stimuli-induced expression of certain mucin genes has been demonstrated to occur
      as a result of ligand-dependent activation of the epidermal growth factor
      receptor (EGFR). In particular, MUC5AC expression can be induced by cigarette
      smoke, neutrophil elastase and lipopolysaccharide (LPS) following activation of
      tumour necrosis factor alpha-converting enzyme. We now show that a large of
      number of stimuli relevant to the cystic fibrosis lung - neutrophil elastase,
      LPS, Pam3Cys-Ser-(Lys)4 Hydrochloride (a lipopeptide analogue), CpG DNA (which
      mimics bacterial DNA) and cystic fibrosis bronchoalveolar lavage fluid - can
      activate MUC1 and 2 expression as well as MUC5AC expression in lung epithelial
      cells via an EGFR-dependent mechanism. In addition, we demonstrate that the
      immunomodulatory anti-protease, secretory leucoprotease inhibitor, can inhibit
      stimuli-induced MUC1, 2 and 5AC expression via a mechanism that is primarily
      dependent on the inhibition of transforming growth factor type alpha release.
      Therefore, mucin gene expression, induced by cystic fibrosis respiratory stimuli,
      can be inhibited by secretory leucoprotease inhibitor indicating its potential
      importance as an anti-mucin agent in cystic fibrosis and other chronic lung
      diseases characterized by mucus hypersecretion.

PMID- 17026479
TI  - Histones and histone modifications in protozoan parasites.
AB  - Protozoan parasites are early branching eukaryotes causing significant morbidity
      and mortality in humans and livestock. Single-celled parasites have evolved
      complex life cycles, which may involve multiple host organisms, and strategies to
      evade host immune responses. Consequently, two key aspects of virulence that
      underlie pathogenesis are parasite differentiation and antigenic variation, both
      of which require changes in the expressed genome. Complicating these requisite
      alterations in the parasite transcriptome is chromatin, which serves as a
      formidable barrier to DNA processes including transcription, repair, replication
      and recombination. Considerable progress has been made in the study of chromatin
      dynamics in other eukaryotes, and there is much to be gained in extending these
      analyses to protozoan parasites. Much of the work completed to date has focused
      on histone acetylation and methylation in the apicomplexans and trypanosomatids.
      As we describe in this review, such studies provide a unique vantage point of the
      evolutionary picture of eukaryotic cell development, and reveal unique phenomena
      that could be exploited pharmacologically to treat protozoal diseases.

PMID- 17026480
TI  - Does Pseudomonas aeruginosa use intercellular signalling to build biofilm
      communities?
AB  - Pseudomonas aeruginosa is a Gram-negative bacterial species that causes several
      opportunistic human infections. This organism is also found in the environment,
      where it is renowned (like other Pseudomonads) for its ability to use a wide
      variety of compounds as carbon and energy sources. It is a model species for
      studying group-related behaviour in bacteria. Two types of group behaviour it
      engages in are intercellular signalling, or quorum sensing, and the formation of
      surface-associated communities called biofilms. Both quorum sensing and biofilm
      formation are important in the pathogenesis of P. aeruginosa infections. Quorum
      sensing regulates the expression of several secreted virulence factors and quorum
      sensing mutant strains are attenuated for virulence in animal models. Biofilms
      have been implicated in chronic infections. Two examples are the chronic lung
      infections afflicting people suffering from cystic fibrosis and colonization of
      indwelling medical devices. This review will discuss quorum sensing and biofilm
      formation and studies that link these two processes.

PMID- 17026481
TI  - Non-lipooligosaccharide-mediated signalling via Toll-like receptor 4 causes fatal
      meningococcal sepsis in a mouse model.
AB  - Meningococcal lipooligosaccharide (LOS) is a major inflammatory mediator of
      fulminant meningococcal sepsis and meningitis with disease severity correlating
      with circulating concentrations of LOS and proinflammatory cytokines. In this
      study we show that the proinflammatory response to live meningococci in a mouse
      model of sepsis involves TLR4, but can develop independently of the expression of
      LOS. This is supported by data showing that in vivo an isogenic LOS-deficient
      strain, lpxA, induced equivalent disease severity and similar proinflammatory
      responses as the serogroup C wild-type parent strain FAM20. This response was
      abolished in TLR4-/- mice, and neither the wild-type strain of meningococci nor
      the LOS-deficient mutant was able to cause fatal sepsis in these mice. Mouse
      survival correlated with low levels of cytokines and chemokines, the chemotactic
      complement factor C5a and neutrophil levels in blood at 24 h post infection.
      These data suggest that during meningococcal sepsis the recognition of one or
      more unidentified non-LOS component(s) by TLR4 is important in stimulating
      proinflammatory responses, and that fatality associated with meningococcal sepsis
      in mice is induced by the proinflammatory host response.

PMID- 17026482
TI  - Haemolysin produced by Vibrio mimicus activates two Cl- secretory pathways in
      cultured intestinal-like Caco-2 cells.
AB  - Haemolysin (VMH) is a virulent factor produced by Vibrio mimicus, a human
      pathogen that causes diarrhoea. As intestinal epithelial cells are the primary
      targets of haemolysin, we investigated its effects on ion transport in human
      colonic epithelial Caco-2 cells. VMH increased the cellular short circuit current
      (Isc), used to estimated ion fluxes, and 125I efflux of the cells. The VMH
      induced increases in Isc and 125I efflux were suppressed by depleting Ca2+ from
      the medium or by pretreating the cells with BAPTA-AM or by Rp-adenosin 3',5'
      cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). The Cl- channel
      inhibitors 4,4'-disothiocyanatostibene-2,2'-disulfonic acid (DIDS),
      glybenclamide, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) suppressed
      the VMH-induced increases in Isc and 125I efflux. Moreover, VMH increased the
      intracellular concentrations of Ca2+ and cAMP. Thus, VMH stimulates Caco-2 cells
      to secrete Cl- by activating both Ca2+ -dependent and cAMP-dependent Cl-
      secretion mechanisms. VMH forms ion-permeable pores in the lipid bilayer that are
      non-selectively permeable to small ions. However, the ion permeability of these
      pores was not inhibited by glybenclamide and DIDS, and VMH did not change the
      cell membrane potential. These observations indicate that the pores formed on the
      cell membrane by VMH are unlikely to be involved in VMH-induced Cl- secretion.
      Notably, VMH stimulated fluid accumulation in the iliac loop test that was fully
      suppressed by a combination of DIDS and glybenclamide. Thus, Ca2+-dependent and
      cAMP-dependent Cl- secretion may be important therapeutic targets with regard to
      the diarrhoea that is induced by Vibrio mimicus.

PMID- 17026483
TI  - AMP-activated protein kinase: Role in metabolism and therapeutic implications.
AB  - AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which
      becomes activated in situations of energy consumption. AMPK functions to restore
      cellular ATP levels by modifying diverse metabolic and cellular pathways. In the
      skeletal muscle, AMPK is activated during exercise and is involved in contraction
      stimulated glucose transport and fatty acid oxidation. In the heart, AMPK
      activity increases during ischaemia and functions to sustain ATP, cardiac
      function and myocardial viability. In the liver, AMPK inhibits the production of
      glucose, cholesterol and triglycerides and stimulates fatty acid oxidation.
      Recent studies have shown that AMPK is involved in the mechanism of action of
      metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin.
      These data, along with evidence that pharmacological activation of AMPK in vivo
      improves blood glucose homeostasis, cholesterol concentrations and blood pressure
      in insulin-resistant rodents, make this enzyme an attractive pharmacological
      target for the treatment of type 2 diabetes, ischaemic heart disease and other
      metabolic diseases.

PMID- 17026484
TI  - Role of leptin in the cardiovascular and endocrine complications of metabolic
      syndrome.
AB  - AIM: To review the potential role of leptin, hyperleptinaemia and leptin
      resistance in the cardiovascular and endocrine complications of metabolic
      syndrome. METHODS: Review of literature listed in Medline. RESULTS:
      Hyperleptinaemia is common in obesity and reflects increased adiposity and leptin
      resistance. Nevertheless, leptin resistance may not be complete as several
      actions of leptin, such as cardiovascular sympatho-activation, might be preserved
      in obese subjects known to be resistant to the metabolic effects of leptin (i.e.
      selective leptin resistance). Notably, the renal and sympathetic actions of
      leptin may play an important role in the pathogenesis of hypertension related to
      obesity and metabolic syndrome. Furthermore, the lipotoxic effect of leptin
      resistance may cause insulin resistance and beta cell dysfunction, increasing the
      risk of type 2 diabetes. Leptin has also been shown to possess proliferative, pro
      inflammatory, pro-thrombotic, and pro-oxidative actions. CONCLUSION:
      Hyperleptinaemia and leptin resistance may contribute to hypertension, impaired
      glucose metabolism, and pro-atherogenic state in obesity and metabolic syndrome.

PMID- 17026485
TI  - Novel insulin analogues and its mitogenic potential.
AB  - Insulin analogues were developed to modify the structure of the human insulin
      molecule in order to more accurately approximate the endogenous secretion of
      insulin. With the help of recombinant technology and site-directed mutagenesis,
      the insulin molecule can be modified to either delay or shorten absorption time,
      providing better insulin treatment options and facilitating the achievement of
      glycaemic goals. Changing the structure of the insulin molecule, however, may
      significantly alter both its metabolic and mitogenic activity. Multiple factors
      such as residence time on the receptor, dissociation rate, rate of receptor
      internalization and the degree of phosphorylation of signalling proteins can
      affect the mitogenic potencies of insulin analogues. Changes in the structure of
      the insulin have raised concern about the safety of the insulin analogues. For
      example, questions have emerged about the relationship between the use of insulin
      lispro and insulin glargine and the progression of diabetic retinopathy. Two
      studies have shown progression of retinopathy with the use of insulin lispro.
      However, others have not confirmed these results, and causality could not be
      proven as progression of retinopathy can occur with rapid improvement in
      glycaemic control, and methods of assessments among studies were not consistent.
      Therefore, we examine the metabolic and mitogenic characteristics of the three
      insulin analogues, insulin lispro, insulin aspart and insulin glargine, that are
      currently on the market, as well as the two insulin analogues, insulin glulisine
      and insulin detemir, that are soon going to be available for clinical use.

PMID- 17026486
TI  - Catecholamine storage vesicles and the metabolic syndrome: The role of the
      chromogranin A fragment pancreastatin.
AB  - Chromogranins or secretogranins (granins), present in secretory granules of
      virtually all neuroendocrine cells and neurones, are structurally related
      proteins encoded by different genetic loci: chromogranins A and B, and
      secretogranins II through VI. Compelling evidence supports both intracellular and
      extracellular functions for this protein family. Within the cells of origin, a
      granulogenic or sorting role in the regulated pathway of hormone or
      neurotransmitter secretion has been documented, especially for chromogranin A
      (CHGA). Granins also function as pro-hormones, giving rise by proteolytic
      processing to an array of peptide fragments for which diverse autocrine,
      paracrine, and endocrine activities have been demonstrated. CHGA measurements
      yield insight into the pathogenesis of such human diseases as essential
      hypertension, in which deficiency of the catecholamine release-inhibitory CHGA
      fragment catestatin may trigger sympathoadrenal overactivity as an aetiologic
      culprit in the syndrome. The CHGA dysglycaemic fragment pancreastatin is
      functional in humans in vivo, affecting both carbohydrate (glucose) and lipid
      (fatty acid) metabolism. Pancreastatin is cleaved from CHGA in hormone storage
      granules in vivo, and its plasma concentration varies in human disease. The
      pancreastatin region of CHGA gives rise to three naturally occurring human
      variants, one of which (Gly297Ser) occurs in the functionally important carboxy
      terminus of the peptide, and substantially increases the peptide's potency to
      inhibit cellular glucose uptake. These observations establish a role for
      pancreastatin in human intermediary metabolism and disease, and suggest that
      qualitative hereditary alterations in pancreastatin's primary structure may give
      rise to interindividual differences in glucose disposition.

PMID- 17026487
TI  - Inhaled insulin delivery--where are we now?
AB  - Since 1925, when the concept of treating diabetes with inhaled insulin (INH) was
      originally published, a number of clinical challenges have been resolved through
      technological advancements. Efforts by pharmaceutical partnerships or individual
      companies have resulted in the development of both injection-free devices and
      novel insulin formulations. Four different INH systems are now in phase 3 of
      clinical development, and several other INH systems are in earlier stages of
      clinical study. Clinical data consistently demonstrate that INH therapy is
      comparable to subcutaneous (SC) therapy in improving glycaemic control in
      patients with either type 1 or type 2 diabetes, generally without greater risk of
      overall hypoglycaemia. INH is generally well tolerated and appears to be safe.
      Adverse-event profiles for INH therapies are similar to SC insulin therapy, with
      the majority of events being reported as being mild to moderate. Long-term safety
      studies are ongoing, with emphasis on evaluating the impact of INH therapy on
      pulmonary function and immune responses. Although small, reversible decreases in
      pulmonary diffusion capacity (DL(co)) and FEV1 have been reported in response to
      INH, pulmonary function and structure do not appear to be affected in any
      clinically significant way. While insulin antibodies are increased in INH
      therapy, these antibodies have not been correlated with haemoglobin A1c (HbA1c),
      insulin dosage, hypoglycaemia, pulmonary function or adverse events.
      Nevertheless, properly controlled, long-term studies will best answer any
      remaining concerns. From the patient's perspective, INH therapy is preferred by
      the majority of patients over conventional SC insulin therapy. Studies have shown
      that patients prefer INH therapy, because it provides greater lifestyle
      flexibility and social acceptability while at the same time avoiding the pain
      associated with injection. Thus, after more than 80 years during which the
      injection route has been the only means of administering insulin, patients and
      physicians may soon avail themselves of another valuable tool in management of
      diabetes.

PMID- 17026488
TI  - Improvement in glycaemic control with rosiglitazone/metformin fixed-dose
      combination therapy in patients with type 2 diabetes with very poor glycaemic
      control.
AB  - OBJECTIVE: Traditional first-line intervention in patients with type 2 diabetes
      and very poor glycaemic control is insulin therapy or high doses of sulfonylureas
      if there is no evidence of volume depletion. This study explored the safety and
      efficacy of open-label treatment with rosiglitazone and metformin (RSG/MET) fixed
      dose combination therapy (AVANDAMET) in patients with type 2 diabetes with very
      poor glycaemic control, to better characterize the magnitude of glycated
      haemoglobin (A1c) reduction after 24 weeks of therapy. METHODS: In this
      multicentre, open-label trial, 190 patients with an A1c greater than 11% or
      fasting plasma glucose (FPG) greater than 15 mmol/l were included after failing
      to meet glycaemic entry criteria for a primary double-blind, controlled,
      randomized study. Unless tolerability issues arose, eligible patients initiated
      RSG/MET 4 mg/1000 mg fixed-dose combination therapy and were up-titrated in
      increments of 2 mg/500 mg at 4-week intervals to a daily dose of 8 mg/2000 mg or
      the maximum tolerated dose. Patients were assessed for efficacy and safety at
      five visits over a 24-week period. The primary efficacy end point was change from
      baseline in A1c at week 24. Secondary efficacy end points included the proportion
      of patients achieving defined A1c targets, change from baseline to week 24 in FPG
      and insulin sensitivity. RESULTS: The majority of patients (78%) completed 24
      weeks of open-label treatment. At week 24, clinically significant mean reduction
      in A1c from 11.8 to 7.8% (mean reduction, 4.0 +/- 2.2%; p < 0.0001) and mean FPG
      reduction from 16.9 to 9.2 mmol/l (mean reduction, 7.7 +/- 4.4 mmol/l; p <
      0.0001) were observed. A clinically significant reduction in FPG (5.2 mmol/l) was
      observed after 4 weeks of treatment with RSG/MET fixed-dose combination therapy.
      Despite a high mean baseline A1c of 11.8%, 33% of patients achieved treatment
      goal of A1c less than or equal to 6.5% at week 24, and 44% achieved an A1c less
      than 7% at week 24. RSG/MET fixed-dose combination was well tolerated, with a low
      incidence of hypoglycaemia (2%) and mean increase in weight from baseline of 2.6
      +/- 5.2 kg, and few patients withdrew (2.6%) because of an adverse event.
      CONCLUSIONS: RSG/MET fixed-dose combination therapy was effective as initial
      therapy in patients with type 2 diabetes and very high levels of A1c and/or FPG,
      as demonstrated by robust and relatively rapid improvements in glycaemic control.
      RSG/MET fixed-dose combination was well tolerated as first-line therapy with no
      new tolerability issues identified.

PMID- 17026489
TI  - Initial treatment with rosiglitazone/metformin fixed-dose combination therapy
      compared with monotherapy with either rosiglitazone or metformin in patients with
      uncontrolled type 2 diabetes.
AB  - AIM: This study assessed the efficacy and safety of rosiglitazone and metformin
      (RSG/MET) fixed-dose combination (AVANDAMET) as initial therapy in patients with
      uncontrolled type 2 diabetes compared with monotherapy with either RSG or MET
      after 32 weeks of treatment. METHODS: A total of 468 drug-naive patients with
      uncontrolled type 2 diabetes were recruited for this multicentre, double-blind
      trial if their glycated haemoglobin (A1c) was greater than 7.5%, but less than or
      equal to 11%, and their fasting plasma glucose (FPG) was less than or equal to 15
      mmol/l. Patients were randomized to 32 weeks of blinded treatment with either
      RSG/MET fixed-dose combination (n = 155), MET (n = 154) or RSG (n = 159). The
      groups were comparable at baseline, with mean A1c of 8.8% and FPG of 11 mmol/l.
      RSG/MET was initiated with a total daily dose of 2 mg/500 mg and could be
      increased up to 8 mg/2000 mg; MET therapy began with a total daily dose of 500 mg
      and could be increased up to 2000 mg; and RSG treatment began with a total daily
      dose of 4 mg and could be increased up to 8 mg. Medication was uptitrated during
      on-therapy visits based on failure to attain glycaemic target of mean daily
      glucose less than or equal to 6.1 mmol/l (unless at maximum tolerated dose).
      Patients were assessed for efficacy and safety at nine visits over a 32-week
      treatment period. This was a trial designed to show greater efficacy of RSG/MET
      combination therapy compared with MET or RSG monotherapy. The primary end point
      was change in A1c from baseline to week 32. Secondary end points included the
      proportion of patients achieving recommended A1c and FPG targets for glycaemic
      control and change from baseline in FPG, free fatty acid, lipids, insulin,
      insulin sensitivity, C-reactive protein and adiponectin. Safety evaluations
      included adverse-event (AE) monitoring, changes in weight and clinical laboratory
      evaluations. RESULTS: At week 32, RSG/MET showed significant improvements in A1c
      from a baseline of 8.9 +/- 1.1% to 6.6 +/- 1.0% at study end, and this 2.3%
      reduction was significantly greater than the reductions achieved individually
      with MET (-1.8%; p = 0.0008) and RSG (-1.6%; p < 0.0001). The greatest mean
      decrease in FPG was seen with RSG/MET (-4.1 mmol/l) and was significant compared
      with MET (-2.8 mmol/l; p < 0.0001) and RSG (-2.6 mmol/l; p < 0.0001). Target A1c
      of less than or equal to 6.5% and less than 7% were achieved in more patients in
      the RSG/MET group (60% and 77%) than with MET (39% and 57%) or RSG (35% and 58%)
      respectively. Treatment was well tolerated, with nausea, vomiting and diarrhoea
      as the most commonly reported AEs. Oedema was comparable between RSG/MET (6%) and
      RSG (7%) and lower in the MET group (3%). No new safety and tolerability issues
      were observed in the RSG/MET group. CONCLUSIONS: As first-line therapy in
      patients with uncontrolled type 2 diabetes, RSG/MET fixed-dose combination
      therapy achieved significant reductions in A1c and FPG compared with either RSG
      or MET monotherapy. RSG/MET was generally well tolerated as initial therapy, with
      no new tolerability issues identified with the fixed-dose combination.

PMID- 17026490
TI  - Effect of nelfinavir on insulin metabolism, proteasome activity and protein
      degradation in HepG2 cells.
AB  - HIV-1 protease inhibitors have revolutionized the treatment of HIV infection, but
      their use has been associated with lipodystrophy and insulin resistance. One
      suggestion for this has been the inhibition of insulin-degrading enzyme (IDE). We
      have previously demonstrated that insulin, through IDE, can inhibit the
      proteasome, thus decreasing cytosolic protein degradation. We examined whether
      the protease inhibitor nelfinavir inhibited IDE and its effect on protein
      degradation both in vitro and in whole cells. 125I-Insulin degradation was
      measured by trichloroacetic acid precipitation. Proteasome activities were
      measured using fluorogenic peptide substrates. Cellular protein degradation was
      measured by prelabelling cells with 3H-leucine and determining the release of TCA
      soluble radioactivity. Nelfinavir inhibited IDE in a concentration-dependent
      manner with 50% inhibition at the maximal concentration tested, 100 microm.
      Similarly, the chymotrypsin-like and trypsin-like activities of the proteasome
      were decreased with an IC50 of approximately 3 microm. The ability of insulin to
      inhibit the proteasome was abrogated by nelfinavir. Treatment of HepG2 cells with
      50 microm nelfinavir decreased 125I-insulin degradation and increased cell
      associated radioactivity. Insulin alone maximally decreased protein degradation
      by 15%. Addition of 50 microm nelfinavir inhibited cellular protein degradation
      by 14% and blunted the effect of insulin. These data show that nelfinavir
      inhibits IDE, decreases insulin's ability to inhibit protein degradation via the
      proteasome and provides another possible mechanism for the insulin resistance
      seen in protease inhibitor-treated HIV patients.

PMID- 17026491
TI  - Weight gain and insulin requirement in type 2 diabetic patients during the first
      year after initiating insulin therapy dependent on baseline BMI.
AB  - AIM: The aim of this study was to determine differences, if any, in weight gain
      and increased insulin requirements in insulin-treated type 2 diabetic patients
      with a normal and an elevated body mass index (BMI). METHODS: A total of 192
      patients with newly insulinized type 2 diabetes were included in the study. The
      patients were divided into three groups: those with BMI <26 (n = 102), BMI 26-30
      (n = 50) and those with BMI >30 (n = 40). At the beginning of insulin therapy and
      12 months later, we compared HbA1c, BMI and required insulin doses in each group
      and evaluated weight gain and the increase in insulin requirement during the
      observation period. Moreover, we investigated the influence of additional
      metformin therapy on weight gain and insulin requirement. RESULTS: Body weight
      increased in the group with normal BMI from 68.8 +/- 9.2 to 70.8 +/- 9.4 kg
      (+2.9%) and in the other groups from 79.0 +/- 9.3 to 81.2 +/- 8.4 (+2.8%) and
      from 96.2 +/- 11.2 to 99.1 +/- 16.5 kg (+3.0%) respectively. The differences
      between the groups were not significant. The insulin requirement increased by 22%
      in the normal-weighted group and by 23% in both groups with overweight. The
      reduction in mean HbA1c was similar in the three groups (22, 18 and 22%). Under
      additional metformin therapy, the increment of insulin requirement of all
      patients (n = 40) was significantly lower (11 vs. 26%, p < 0.01), and there was
      no significant difference between the groups with different BMIs. During the same
      period, the gain in body weight and the decrease of HbA1c were not significantly
      different in the patients with and without metformin independent on the BMI.
      CONCLUSIONS: The risk for weight gain and increase in insulin requirement is
      similar in insulin-treated type 2 diabetic patients with normal and elevated BMI.
      Additional metformin therapy reduces insulin requirement in patients with and
      without overweight.

PMID- 17026492
TI  - Reduced left ventricular mass after treatment of obese patients with sibutramine:
      An echocardiographic multicentre study.
AB  - AIM: In obesity, left ventricular hypertrophy is frequently observed, especially
      in the presence of hypertension. Following body weight reduction, the left
      ventricular mass (LVM) is reduced. It is not known to which extent this occurs
      after treatment with sibutramine. METHODS: In this multicentre trial, 195 male
      and female patients (18-65 years of age, body mass index 30-40 kg/m2) were
      treated for 12 weeks with either 15 mg/day sibutramine or placebo. They were
      advised to follow mildly hypocaloric reducing diets. Exclusion criteria were
      blood pressure values >180/110 mmHg and tachycardia (heart rate > or =100
      beats/min). Echocardiography in M-mode was performed to determine LVM as well as
      systolic function. RESULTS: Body weight was reduced by 6.9 +/- 0.3 kg under
      sibutramine and by 2.1 +/- 0.6 kg under placebo; body fat was reduced by 5.2 +/-
      0.4 kg and 1.6 +/- 0.7 kg respectively. In the sibutramine group, LVM was reduced
      by 10.9 +/- 24.2 g; LVM indexed for body surface area was reduced by 2.3 +/- 11.8
      g/m2 and LVM indexed for body height was reduced by 2.5 +/- 6.0 g/m(2.7). In the
      placebo group, LVM and LVM indices were not significantly changed. Changes in LVM
      correlated with reductions in body weight and initial LVM but not with changes in
      blood pressure or heart rate. CONCLUSIONS: After 3 months of treatment with
      sibutramine, obese patients lost about three times as much of body weight and LVM
      than patients treated with placebo. Therefore, sibutramine may be recommended not
      only to reduce body weight but also to obtain a regression of the LVM in obese
      patients with and without hypertension.

PMID- 17026493
TI  - Multiple mealtime administration of biphasic insulin aspart 30 versus traditional
      basal-bolus human insulin treatment in patients with type 1 diabetes.
AB  - AIM: The aim of this study was to compare the effect of multiple mealtime
      injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the
      formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on
      glycaemic control in patients with type 1 diabetes. METHODS: Twenty-three
      patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range)
      with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All
      eligible patients were randomly assigned to BIAsp30 thrice daily supplied with
      bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then
      switched to the alternative regimen for another 12 weeks. The insulin dose
      adjustments were made by patients on the basis of advice from a diabetes nurse.
      At end of each treatment period, the patients attended two profile days, 1 week
      apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at
      baseline and at the end of each treatment period. A seven-point self-monitored
      blood glucose (SMBG) was obtained twice weekly. RESULTS: In comparison with HI,
      multiple mealtime injections of BIAsp30 resulted in a significant reduction in
      HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7
      9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was
      significantly improved. Day-to-day variation in pharmacodynamics and
      pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30
      compared with HI. CONCLUSIONS: In type 1 diabetics, multiple mealtime
      administration of BIAsp30 compared with traditional basal-bolus human insulin
      treatment significantly improves long-term glycaemic control without increasing
      the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting
      insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day
      variations in insulin pharmacokinetics and pharmacodynamics.

PMID- 17026494
TI  - The metabolic syndrome in type 2 diabetes: When does it matter?
AB  - AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the
      problem of when to start therapies for the primary prevention of vascular disease
      and how to identify those at most vascular risk. We examine whether the metabolic
      syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this
      context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects
      were categorized as having MetS by World Health Organization criteria (body mass
      index criteria modified for Asians using >23 kg/m2). The prevalence of
      macrovascular disease was examined by MetS status and age. RESULTS: The overall
      MetS prevalence was 72.3%. MetS was associated with an increased prevalence of
      ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001),
      coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular
      disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across
      all age groups. MetS subjects had an IHD prevalence equivalent to that seen in
      subjects who were one decade older without MetS. The most significant impact of
      MetS was for the age group of 40-49 years with much lesser impact seen with
      progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with
      no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age
      >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft
      (CABG) and PVD. There was a strong relationship between the number of MetS risk
      factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data
      suggest that MetS is particularly useful in stratifying vascular risk in younger
      T2Dm patients and in those with a high number of MetS components. For patients
      with MetS, especially those with a full house of MetS risk factors, commencing
      risk-lowering interventions 10 years earlier than their MetS-free counterparts
      could be considered.

PMID- 17026495
TI  - Measurement of liver fat by magnetic resonance imaging: Relationships with body
      fat distribution, insulin sensitivity and plasma lipids in healthy men.
AB  - AIM: We compared the use of magnetic resonance imaging (MRI) as a test for liver
      fat content (LFAT) with proton magnetic resonance spectroscopy (MRS) and
      investigated its relationship with body fat distribution, insulin sensitivity,
      plasma lipids and lipoproteins. METHODS: LFAT was quantified by MRI and MRS in 17
      free-living, healthy men with a wide range of body mass indexes. Fasting
      adiponectin was measured by immunoassay and insulin resistance by homeostasis
      assessment (HOMA) score. Intraperitoneal, retroperitoneal, anterior subcutaneous
      and posterior subcutaneous abdominal adipose tissue masses (ATMs) were determined
      by MRI. RESULTS: Measurements of LFAT by MRI and MRS were highly correlated (r =
      0.851, p < 0.001). In univariate regression analysis, LFAT by MRI was also
      significantly correlated with plasma triglycerides (TGs), insulin, HOMA score,
      carbohydrate intake and the masses of all abdominal adipose tissue compartments
      (p < 0.05). LFAT was inversely correlated with plasma adiponectin (r = -0.505, p
      < 0.05). In multivariate linear regression analysis including plasma adiponectin
      and age, intraperitoneal ATM was an independent predictor of LFAT (beta
      coefficient = 0.587, p = 0.024). Moreover, intraperitoneal ATM was also an
      independent predictor of HOMA score after adjusting for LFAT, plasma adiponectin
      and age (beta-coefficient = 0.810, p = 0.010). Conversely, LFAT was a significant
      predictor of plasma TG concentration after adjusting for adiponectin,
      intraperitoneal ATM, HOMA and age (beta-coefficient = 0.751, p = 0.007). Similar
      findings applied with LFAT measured by MRS. CONCLUSIONS: These data suggest that
      MRI is as good as MRS to quantify liver fat content. Our data also suggest that
      liver fat content could link intraabdominal fat with insulin resistance and
      dyslipidaemia.

PMID- 17026496
TI  - Obesity risk associated with the K121Q polymorphism of the glycoprotein PC-1
      gene.
AB  - BACKGROUND: Obesity is considered to be a multifactorial trait resulting from the
      combined influence of genetic and environmental determinants. Insulin resistance
      plays an important role in the development of obesity. Plasma-cell membrane
      differentiation antigene-1 (PC-1) inhibits insulin receptor signalling when
      overexpressed and thus causes insulin resistance. PC-1 gene polymorphism might be
      associated with adipocyte metabolism disturbance and energy imbalance. The
      purpose of this study was to determine whether K121Q polymorphism in PC-1 gene is
      involved in obesity susceptibility in Chinese Han population. METHODS: The
      genotype of the polymorphism was determined using polymerase chain reaction
      restriction fragment length polymorphism analysis for 338 unrelated subjects of
      Beijing, China. Their Body mass index (BMI), plasma glucose, total cholesterol,
      triglyceride, high-density lipoprotein cholesterol (HDL), free fatty acid (FFA)
      and insulin level were measured. Chi-square analyses were applied to test the
      significance differences in genotypic and allelic frequencies. Association
      studies were undertaken using the t-test and logistic regression analyses.
      RESULTS: The obese had significantly higher frequency of KQ/QQ genotype or Q
      allele than non-obese in females (26.7% vs. 10.9%, p = 0.014 and 13.3% vs. 5.5%,
      p = 0.021). Significant elevation of insulin amongst the Q121 carrier women in
      obesity individuals and higher FFA level of Q121 carrier men in non-obese
      controls (BMI < or = 23 kg/m2) were observed. Binary logistic regression analysis
      revealed that PC-1 genotype together with higher glucose, total cholesterol,
      triglyceride and serum HDL were independently associated with the presence of
      obesity. CONCLUSIONS: The observed genotype distributions revealed a significant
      association of PC-1 K121Q with obesity. PC-1 Q121 carriers are more likely to be
      insulin-resistant or get fatter in respect to KK subjects and carriers of the Q
      allele are at higher risk for the development of obesity in female.

PMID- 17026497
TI  - Variant K of butyrylcholinesterase and risk of early-onset type 1 diabetes
      mellitus in Euro-Brazilians.

PMID- 17026498
TI  - Re-feeding syndrome following adjustable gastric banding.

PMID- 17026499
TI  - Hyperbaric exposure with high oxygen concentration inhibits growth-associated
      increase in the glucose level of diabetic Goto-Kakizaki rats.

PMID- 17026500
TI  - Runx2 and dental development.
AB  - The Runx2 gene is a master transcription factor of bone and plays a role in all
      stages of bone formation. It is essential for the initial commitment of
      mesenchymal cells to the osteoblastic lineage and also controls the
      proliferation, differentiation, and maintenance of these cells. Control is
      complex, with involvement of a multitude of factors, thereby regulating the
      expression and activity of this gene both temporally and spatially. The use of
      multiple promoters and alternative splicing of exons further extends its
      diversity of actions. RUNX2 is also essential for the later stages of tooth
      formation, is intimately involved in the development of calcified tooth tissue,
      and exerts an influence on proliferation of the dental lamina. Furthermore, RUNX2
      regulates the alveolar remodelling process essential for tooth eruption and may
      play a role in the maintenance of the periodontal ligament. In this article, the
      structure of Runx2 is described. The control and function of the gene and its
      product are discussed, with special reference to developing tooth tissues, in an
      attempt to elucidate the role of this gene in the development of the teeth and
      supporting structures.

PMID- 17026501
TI  - Detection of pemphigus desmoglein 1 and desmoglein 3 autoantibodies and
      pemphigoid BP180 autoantibodies in saliva and comparison with serum values.
AB  - Although there is much literature on the detection of pemphigus and pemphigoid
      autoantibodies by enzyme-linked immunosorbent assay (ELISA) in serum, nothing is
      known about their presence in saliva. The aim of this study was to evaluate the
      salivary levels of these autoantibodies in pemphigus and pemphigoid patients.
      Autoantibodies against desmoglein3, desmoglein1, and BP180 were assayed, by
      ELISA, in serum and saliva samples of patients and healthy controls. The titres
      of autoantibodies against Dsg1/3 found in both serum and saliva of pemphigus
      patients showed a statistically significant correlation, suggesting that saliva
      may be a useful biological material for diagnostic purposes, in monitoring
      disease activity, as well as for the early detection of relapses. By contrast,
      the titres of autoantibodies against BP180 in the serum and saliva of bullous
      pemphigoid patients were not statistically related, and further study of the
      usefulness of the BP180 ELISA for saliva in this disease is needed. In addition,
      based on our results, the BP180 ELISA with a recombinant NC16a epitope failed to
      detect the autoantibodies against BP180 in the serum and saliva of mucous
      membrane pemphigoid patients.

PMID- 17026502
TI  - Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis
      imperfecta type II.
AB  - Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder
      affecting dentin. Defective dentin formation results in discolored teeth that are
      prone to attrition and fracture. To date, several mutations have been described
      in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and
      dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP)
      and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP
      in seven Finnish families with DGI type II. We report two mutations and five
      single nucleotide polymorphisms. In one family we found a mutation that has been
      described earlier in families with different ethnicity, while in six families we
      found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known
      DSPP mutations suggests that DGI type II is usually caused by aberration of
      normal splicing.

PMID- 17026503
TI  - Oral health, dental anxiety, and behavior management problems in children with
      attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common developmental
      disorder. The aim of this study was to investigate whether children with ADHD
      have a higher caries prevalence, a higher degree of dental anxiety, or more
      dental behavior management problems (BMP) than children of a control group.
      Twenty-five children with ADHD and a control group of 58 children, all aged 11
      yr, were included in the study. The children underwent a clinical dental
      examination, and bitewing radiographs were taken. The parents completed the
      Dental Subscale of Children's Fear Survey Schedule (CFSS-DS). Dental records from
      the subjects were obtained, and data regarding notes on behavior management
      problems (BMP) of the children when between 3 and 10 yr of age were compiled.
      Compared with controls, children with ADHD had significantly higher decayed,
      missing or filled surfaces (DMFS) (2.0 +/- 3.0 vs. 1.0 +/- 1.5) and significantly
      higher decayed surfaces (DS) (1.7 +/- 3.6 vs. 0.5 +/- 0.9). Differences between
      the groups regarding CFSS-DS scores were non-significant. In the ADHD group, the
      prevalence of BMP increased when the children were between 7 and 9 yr of age. In
      conclusion, children with ADHD exhibited a higher caries prevalence, did not
      exhibit a higher degree of dental anxiety, and had more BMP than children of a
      control group.

PMID- 17026504
TI  - Clinical correlates of oral health-related quality of life: evidence from a
      national sample of British older people.
AB  - This study investigated the relationships between an oral health-related quality
      of life (OHRQoL) indicator and specific clinical dental measures, in a national
      representative sample of the British older population. A random subsample was
      drawn from the free-living sample of the National Diet and Nutrition Survey
      (people aged >or= 65 yr). This subsample consisted of 407 dentate and 346
      edentate participants, who were clinically examined and interviewed. The OHRQoL
      was assessed through the Oral Impacts on Daily Performance (OIDP) indicator.
      After adjusting for age, gender, and education, dentate subjects with up to 8
      occluding pairs of teeth were 2.66 [95% confidence interval (CI): 1.08, 6.51)
      times, and those with up to 2 anterior occluding pairs were 3.00 (95% CI: 1.55,
      5.81) times, more likely to report oral impacts when compared with those having
      more occluding pairs of teeth. Edentate participants with inadequate denture
      adaptation were 1.92 (95% CI: 1.04, 3.53) times, and subjects with inadequate
      denture retention were 2.04 (95% CI: 1.13, 3.69) times, more likely to report
      oral impacts than the remaining edentate sample in each case. OHRQoL in older
      British people is significantly related to the number of occluding pairs of
      natural teeth among the dentate and denture quality among the edentate.

PMID- 17026505
TI  - Predictors of recall assignment decisions by general dental practitioners
      performing routine oral examinations.
AB  - The aim of this study was to explore the decision-making behavior of general
      dental practitioners (GDPs) in performing routine oral examinations (ROEs).
      Change over time was studied by comparing data from a cohort sample of
      participants in two surveys in 2000 and 2005. A written questionnaire was sent to
      809 dentists (509 responses were obtained) and 475 (61%) were used for analysis.
      Of the respondents, 347 also participated in the survey in 2000. The mean number
      of diagnostic ROE items per ROE was 6.9 (standard deviation = 1.7). Groups of
      GDPs were distinguished based on their answer to the question 'Do you apply for
      all patients a fixed recall interval between two successive ROEs?' and four
      personal profiles. Of the GDPs, 38.5% (n = 183) assigned fixed recall intervals
      (Fxs) for all patients. Individual recall intervals (Ivs) were applied by 61.5%
      (n = 292) of GDPs, depending on specific selected patient characteristics and
      risk factors. Logistic regression showed that GDPs applying Fxs also used fixed
      periods between successive bitewing radiographs. Furthermore, GDPs applying Ivs
      conducted more frequent periodontal screening and, in the event of periodontal
      problems, were more inclined to prescribe radiographs. Over a 5 yr period, a
      shift towards Ivs assignment (from 49% in 2000 to 61.5% in 2005) was found.
      Differences in assigned recall intervals (Fxs/Ivs) by GDPs are determined by
      three clinical ROE predictors and two GDP profiles. A shift towards a more
      individual assessment was found between 2000 and 2005 in the way that Dutch GDPs
      are dealing with the assignment of recall interval frequency.

PMID- 17026506
TI  - Smoking modulates interferon-gamma expression in the gingival tissue of patients
      with chronic periodontitis.
AB  - Although interferon-gamma (IFN-gamma) plays a critical role in periodontitis, no
      information is available regarding the effect of smoking on this cytokine in the
      periodontium. Therefore, this study aimed to evaluate the effect of smoking on
      the IFN-gamma levels in gingival tissue from patients with chronic periodontitis.
      Sixty-two patients were assigned to three groups: healthy [non-smoking and
      periodontally healthy individuals (probing depth <or= 3 mm and no bleeding on
      probing; n = 12)]; periodontitis [non-smokers clinically diagnosed with moderate
      to severe chronic periodontitis (probing depth >or= 5 mm and bleeding on probing;
      n = 25)]; and smoking [smokers (>or= 1 pack/day for at least 10 yr) diagnosed
      with chronic periodontitis (n = 25)]. Gingival biopsies were analyzed by
      quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.
      Regardless of smoking status, diseased patients presented higher levels of IFN
      gamma than peridontally healthy patients. In sites with comparable types of
      periodontitis, smoking increased both protein and mRNA levels of IFN-gamma in
      gingival tissue. Within the limits of this study, it can be concluded that
      modulation of periodontal tissue destruction by smoking may involve its effect on
      IFN-gamma production.

PMID- 17026507
TI  - Expression of stem cell factor and its receptor, c-kit, in human oral mesenchymal
      cells.
AB  - Stem cell factor (SCF) is the pleiotropic ligand for the tyrosine kinase
      receptor, c-kit. Ligand and receptor are usually expressed in different cell
      types, and binding of SCF to c-kit promotes cell proliferation, differentiation,
      and recruitment of progenitor cells in various biologic systems. However, the
      localization of these two molecules in cells of the oral cavity has not been
      systematically examined. We investigated the expression of SCF and c-kit in human
      dental pulp (HDP) cells as well as in human gingival fibroblasts (HGF). Both
      alternatively spliced isoforms of SCF were detected (through reverse
      transcription-polymerase chain reaction) in RNA obtained from the two cell types.
      Western analysis established that both cell types express SCF and/or c-kit,
      whereas flow cytometry demonstrated distinct cell populations expressing only the
      ligand (SCF), only the receptor (c-kit), or co-expressing the two. HDP cultures
      showed higher soluble SCF (sSCF) production associated with faster cell growth,
      as compared with HGF cultures. In both cell types, however, sSCF levels appeared
      to increase as a result of in vitro aging and/or differentiation.

PMID- 17026508
TI  - Composition changes in gingival crevicular fluid during orthodontic tooth
      movement: comparisons between tension and compression sides.
AB  - The aim of this study was to evaluate whether the application of tension or
      compression forces exerted on the periodontium during the early phase of
      orthodontic tooth movement is reflected by differences in the composition of the
      gingival crevicular fluid (GCF), at the level of interleukin-1beta (IL-1beta),
      substance P (SP), and prostaglandin E(2) (PGE(2)). Eighteen children (mean age
      10.8 yr) starting orthodontic treatment were included in the study. Molar elastic
      separators were inserted mesially to two first upper or lower molars. One of the
      antagonist molars served as the control. GCF was collected from the mesial and
      distal sites of each molar, before (-7 d, 0 d) and immediately after (1 min, 1 h,
      1 d, and 7 d) the placement of separators. The levels of IL-1beta, SP, and PGE(2)
      were determined by enzme-linked immunosorbent assay. At the orthodontically moved
      teeth, the GCF levels of IL-1beta, SP, and PGE(2) were significantly higher than
      at the control teeth in both tension and compression sides, and at almost all
      occasions after insertion of separators. The increase, relative to baseline
      values, was generally higher in tension sides. For the control teeth, the three
      mediators remained at baseline levels throughout the experiment. The results
      suggest that IL-1beta, SP, and PGE(2) levels in the GCF reflect the biologic
      activity in the periodontium during orthodontic tooth movement.

PMID- 17026509
TI  - Interleukin-1alpha and tumor necrosis factor-alpha expression during the early
      phases of orthodontic tooth movement in rats.
AB  - Remodelling of the periodontium after application of mechanical forces
      constitutes the basis of clinical orthodontics and various immunoregulatory
      molecules are involved in this process. The aim of this study was to investigate
      the expression of the cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis
      factor-alpha (TNF-alpha) in dental tissues during the early phases of orthodontic
      tooth movement. Eightteen male Wistar rats were used. All maxillary right first
      molars were moved orthodontically, with a force of 0.5 N, for 3 h, 1 d, and 3 d.
      The contralateral sides served as untreated controls. Parasagittal sections of
      the maxillary molars and the surrounding tissues were subjected to
      immunohistochemical staining for IL-1alpha or TNF-alpha, and were evaluated with
      light microscopy. IL-1alpha and TNF-alpha were expressed in the bone and
      periodontal ligament (PDL) along the roots of the orthodontically moved molars
      and in the gingiva. Increased expression of both cytokines was observed in the
      aforementioned areas after 1 and 3 d of tooth movement. The pulp tissue exhibited
      only minor changes in cytokine expression during tooth movement. The results
      suggest that mechanical stress results in almost immediate inflammatory reactions
      in various dental tissues.

PMID- 17026510
TI  - Longitudinal quantification of incipient carious lesions in postorthodontic
      patients using a fluorescence method.
AB  - The aims of this study were to evaluate the effect of two caries-preventive
      programs, and to apply the laser fluorescence method, DIAGNOdent, for
      longitudinal quantification of changes in incipient carious lesions. Twelve
      subjects with 127 test teeth exhibiting white spot lesions on the buccal surfaces
      after completed orthodontic therapy were enrolled in the study. Visual
      examination was performed at baseline and after 12 months. The subjects were
      divided into two groups: one group received repeated professional tooth cleaning
      combined with oral hygiene instruction; and the control group received repeated
      oral hygiene instruction only. The white spot lesions were measured by DIAGNOdent
      at baseline, and at 3, 6, 9, and 12 months thereafter. There was a significant
      difference in the DIAGNOdent readings between the first and the final
      evaluations. However, there was no statistically significant difference between
      the two treatment groups regarding changes of DIAGNOdent values over time. In
      conclusion, it may be possible to use DIAGNOdent for longitudinal quantification
      of carious lesions on smooth surfaces over a period of 1 yr under in vivo
      conditions. The combination of professional tooth cleaning and oral hygiene
      instruction had a similar efficacy to professional tooth cleaning only for
      promoting the remineralization of white spot lesions.

PMID- 17026511
TI  - Effect of ozone on oral cells compared with established antimicrobials.
AB  - Ozone has been proposed as an alternative antiseptic agent in dentistry based on
      reports of its antimicrobial effects in both gaseous and aqueous forms. This
      study investigated whether gaseous ozone (4 x 10(6) microg m(-3)) and aqueous
      ozone (1.25-20 microg ml(-1)) exert any cytotoxic effects on human oral
      epithelial (BHY) cells and gingival fibroblast (HGF-1) cells compared with
      established antiseptics [chlorhexidine digluconate (CHX) 2%, 0.2%; sodium
      hypochlorite (NaOCl) 5.25%, 2.25%; hydrogen peroxide (H(2)O(2)) 3%], over a time
      of 1 min, and compared with the antibiotic, metronidazole, over 24 h. Cell
      counts, metabolic activity, Sp-1 binding, actin levels, and apoptosis were
      evaluated. Ozone gas was found to have toxic effects on both cell types.
      Essentially no cytotoxic signs were observed for aqueous ozone. CHX (2%, 0.2%)
      was highly toxic to BHY cells, and slightly (2%) and non-toxic (0.2%) to HGF-1
      cells. NaOCl and H(2)O(2) resulted in markedly reduced cell viability (BHY, HGF
      1), whereas metronidazole displayed mild toxicity only to BHY cells. Taken
      together, aqueous ozone revealed the highest level of biocompatibility of the
      tested antiseptics.

PMID- 17026512
TI  - Three-dimensional finite-element model of the human temporomandibular joint disc
      during prolonged clenching.
AB  - In the temporomandibular joint (TMJ), overloading induced by prolonged clenching
      appears to be important in the cascade of events leading to disc displacement. In
      this study, the effect of disc displacement on joint stresses during prolonged
      clenching was studied. For this purpose, finite-element models of the TMJ, with
      and without disc displacement, were used. Muscle forces were used as a loading
      condition for stress analysis during a time-period of 10 min. The TMJ disc and
      connective tissue were characterized as a linear viscoelastic material. In the
      asymptomatic model, large stresses were found in the central and lateral part of
      the disc through clenching. In the retrodiscal tissue, stress relaxation occurred
      during the first 2 min of clenching. In the symptomatic model, large stresses
      were observed in the posterior part of the disc and in the retrodiscal tissue,
      and the stress level was kept constant through clenching. This indicates that
      during prolonged clenching the disc functions well in the asymptomatic joint,
      meanwhile the retrodiscal tissue in the symptomatic joint is subject to excessive
      stress. As this structure is less suitable for bearing large stresses, tissue
      damage may occur. In addition, storage of excessive strain energy might lead to
      breakage of the tissue.

PMID- 17026514
TI  - Growth kinetics of microorganisms isolated from Alaskan soil and permafrost in
      solid media frozen down to -35 degrees C.
AB  - We developed a procedure to culture microorganisms below freezing point on solid
      media (cellulose powder or plastic film) with ethanol as the sole carbon source
      without using artificial antifreezes. Enrichment from soil and permafrost
      obtained on such frozen solid media contained mainly fungi, and further
      purification resulted in isolation of basidiomycetous yeasts of the genera Mrakia
      and Leucosporidium as well as ascomycetous fungi of the genus Geomyces. Contrary
      to solid frozen media, the enrichment of liquid nutrient solutions at 0 degrees C
      or supercooled solutions stabilized by glycerol at -1 to -5 degrees C led to the
      isolation of bacteria representing the genera Polaromonas, Pseudomonas and
      Arthrobacter. The growth of fungi on ethanol-microcrystalline cellulose media at 
      8 degrees C was exponential with generation times of 4.6-34 days, while bacteria
      displayed a linear or progressively declining curvilinear dynamic. At -17 to -0
      degrees C the growth of isolates and entire soil community on 14C-ethanol was
      continuous and characterized by yields of 0.27-0.52 g cell C (g of C-substrate)(
      1), similar to growth above the freezing point. The 'state of maintenance,'
      implying measurable catabolic activity of non-growing cells, was not confirmed.
      Below -18 to -35 degrees C, the isolated organisms were able to grow only
      transiently for 3 weeks after cooling with measurable respiratory and
      biosynthetic (14CO2 uptake) activity. Then metabolic activity declined to zero,
      and microorganisms entered a state of reversible dormancy.

PMID- 17026513
TI  - Predominance of Roseobacter, Sulfitobacter, Glaciecola and Psychrobacter in
      seawater collected off Ushuaia, Argentina, Sub-Antarctica.
AB  - Bacterial diversity in sub-Antarctic seawater, collected off Ushuaia, Argentina,
      was examined using a culture independent approach. The composition of the 16S
      rRNA gene libraries from seawater and seawater contaminated with the water
      soluble fraction of crude oil was statistically different (P value 0.001). In
      both libraries, clones representing the Alphaproteobacteria, Gammaproteobacteria,
      the Cytophaga-Flavobacterium-Bacteroidetes group and unculturable bacteria were
      dominant. Clones associated with the genera Roseobacter, Sulfitobacter, Staleya,
      Glaciecola, Colwellia, Marinomonas, Cytophaga and Cellulophaga were common to
      both the libraries. However, clones associated with Psychrobacter, Arcobacter,
      Formosa algae, Polaribacter, Ulvibacter and Tenacibaculum were found only in
      seawater contaminated with hydrocarbons (Table 1). Further, the percentage of
      clones of Roseobacter, Sulfitobacter and Glaceicola was high in seawater (43%,
      90% and 12% respectively) compared to seawater contaminated with hydrocarbons
      (35%, 4% and 9% respectively). One of the clones F2C63 showed 100% similarity
      with Marinomonas ushuaiensis a bacterium identified by us from the same site.

PMID- 17026515
TI  - Hip and non-spine fracture risk reductions differ among antiresorptive agents:
      Evidence from randomised controlled trials.
AB  - A number of antiresorptive agents reduce the risk of vertebral fractures, but few
      have shown consistent effects on hip and other non-spine fractures. Meta-analysis
      provides a more precise estimate than individual trials when results are
      consistent across pooled trials. Earlier meta-analyses summarised the results for
      vertebral and non-spine fractures. New data have emerged for hormone therapy
      (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed
      recent reports of randomised, placebo-controlled trials with non-spine and/or hip
      fracture data, and used meta-analysis where appropriate to test for heterogeneity
      and derive pooled estimates. The magnitude of effect on hip fracture appears to
      be similar to that for non-spine fracture for each drug, but differs among drugs.
      Based on the current data, ALN reduces the risk of hip and non-spine fracture by
      49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent
      evidence of an effect on these fractures for IBN, calcitonin and raloxifene.

PMID- 17026516
TI  - Lupus erythematosus: clinical and histopathological study of oral manifestations
      and immunohistochemical profile of epithelial maturation.
AB  - BACKGROUND: Lupus erythematosus (LE) is an autoimmune disease of unknown cause.
      Prevalence of oral involvement in patients with LE is uncertain but may vary from
      9 to 45% in patients with systemic disease and from 3 to 20% in patients with
      chronic cutaneous involvement. METHODS: Incidence of oral lesions of LE and their
      clinical aspects were investigated. Their histopathologic features were analyzed,
      and the status of epithelial maturation was assessed through the expression
      patterns of cytokeratins. RESULTS: Twenty-six patients (from 188 examined)
      presented oral lesions of LE. Most of them were females (19) with systemic
      disease (11). Clinical aspects of these lesions varied, and lips and buccal
      mucosa were most affected. Histologically, lesions revealed lichenoid mucositis
      with perivascular infiltrate and thickening of basement. Cytokeratins profile
      showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all
      epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers
      only. CONCLUSIONS: Oral lesions of LE show a variety of aspects, and their
      microscopic features are of a lichenoid mucositis with deep inflammatory
      infiltrate. Cytokeratins expression patterns are of hyperproliferative
      epithelium, and this phenomenon must be analyzed in relation to the inflammatory
      cytokines for a better understanding of the mechanisms of the disease.

PMID- 17026517
TI  - Immunoreactivity of CD99 in invasive malignant melanoma.
AB  - BACKGROUND: CD99, also known as p30/32, is a glycoprotein product of the MIC2
      gene. It was originally utilized in immunohistochemistry as a unique marker for
      Ewing sarcoma, other primitive neuroectodermal tumors, and subsequently in other
      tumors. Its expression in malignant melanoma (MM) has not been well documented,
      with just two isolated cases of MM recently reported. Recent studies have
      documented CD99 expression in a significant percentage of atypical fibroxanthomas
      (AFX), posing potential diagnostic problems in differentiating these two
      entities. As mistaking MM for AFX based on immunohistochemical staining pattern
      has significant consequences, we sought to determine the percentage of invasive
      MM in our archives that have this staining pattern. METHODS: Seventy-eight cases
      of invasive melanoma were retrieved from our files. Each case was stained with
      mouse anti-human CD99 and evaluated for membranous expression. RESULTS: Our
      evaluation revealed that 47 of 78 MM cases (60%) stain positive for CD99.
      CONCLUSION: This study is the first to demonstrate, in a large series, the
      prevalence of CD99 expression in primary cutaneous melanoma. Additionally, this
      introduces in the histologic differential diagnosis of CD99 expressing dermal
      spindle cell lesions.

PMID- 17026518
TI  - Stem cell apoptosis in HIV-1 alopecia.
AB  - BACKGROUND: Diffuse alopecia occurs in almost 7% of HIV-1-infected patients.
      Telogen effluvium is the main pathogenic mechanism involved. Apoptotic
      keratinocytes in the outer root sheath at bulge level was described as the most
      characteristic histopathologic finding of this kind of hair loss. METHODS: A case
      control study was conducted to investigate the occurrence of apoptosis of
      follicular stem cells at the bulge in diffuse alopecia of HIV-1 infection. We
      applied a double-staining procedure to transverse scalp sections from 15 HIV-1
      infected patients and 12 controls, with the monoclonal antibody anticytokeratin
      19 as stem cell marker and TUNEL technique to identify apoptosis. RESULTS: Eighty
      percent of cases and 25% of controls presented at least one double-stained
      follicle. The proportion of positive follicles per section was 48% (+/-7%) for
      cases and 26% (+/-13%) for controls. CONCLUSION: Our study demonstrated that
      diffuse alopecia related to HIV-1 infection represents a hair cycle disturbance
      and that part of the follicular stem cell population become apoptotic in a higher
      proportion than normal subjects. We found no cytotoxic folliculitis. Owing to its
      cell-cycle interaction and caspase-induction capacities, we propose HIV-1 viral
      protein R as a possible follicular stem cell apoptosis inductor.

PMID- 17026519
TI  - Type I interferon-associated cytotoxic inflammation in lichen planus.
AB  - INTRODUCTION: Lichen planus (LP) is an inflammatory autoimmune skin disease of
      unknown origin. Evidence has accumulated that autoreactive cytotoxic CD8(+) T
      lymphocytes cause destruction of keratinocytes. Recent studies suggested that
      type I interferons (IFNs) play a central role in cytotoxic skin inflammation by
      increasing the expression of IP10/CXCR10 and recruiting effector cells via CXCR3.
      Here, we investigated whether type I IFNs are also involved in the pathogenesis
      of LP. PATIENTS AND METHODS: Skin biopsies of altogether 17 donors (seven LP and
      10 healthy controls) were analyzed by immunohistochemistry using monoclonal
      antibodies against CD3, CD4, CD8, CD20, CD68, CXCR3, granzyme B, IP10/CXCL10,
      CD123, and the MxA protein, which is specifically induced by type I IFNs.
      RESULTS: Our analysis revealed a significant expression of the MxA protein in all
      LP skin biopsies, indicating involvement of type I IFNs. Expression of MxA was
      closely associated with the recruitment of CXCR3(+) and granzyme B(+)
      lymphocytes, indicating a Th1-biased cytotoxic immune response. Strong expression
      of the CXCR3 ligand, the interferon-inducible protein IP10/CXCL10, links type I
      IFN expression and recruitment of CXCR3(+) lymphocytes. Plasmacytoid dendritic
      cells (pDCs) appear to be a major source of type I IFNs in LP. DISCUSSION: Our
      observations support the hypothesis that lesional type I IFNs produced by pDCs
      plays an important role in chronic cytotoxic inflammation of LP by recruiting
      cytotoxic effector lymphocytes via IP10/CXCR3 interactions.

PMID- 17026520
TI  - Acral keratosis with eosinophilic dermal deposits: a distinctive clinicopatholgic
      entity or colloid milium redux?
AB  - AIMS: The differential diagnosis of acral keratoses is broad. Encompassing a
      variety of infectious, heritable and degenerative disorders, emphasis upon the
      clinical setting and histologic subtlety are often required to arrive at the
      correct diagnosis. Herein, we report on a series of adult patients who presented
      with agminated or solitary papules of the distal finger found on histologic
      examination to contain amorphous eosinophilic deposits. RESULTS: The eosinophilic
      deposits were found in close proximity to the overlying epithelium and devoid of
      apoptotic keratinocytes, plasma cells, or vascular thickening reminiscent of
      amyloidosis or hyalinosis cutis. Special and immunostains yielded eosinophilic
      material that was elastin and Protein P negative. Despite a similar
      histomorphologic appearance to colloid milium, typical clinical features of this
      entity were not present. CONCLUSION: The etiologic significance of this condition
      is unknown. Potential sources of the material and a discussion of the
      differential diagnosis follow.

PMID- 17026521
TI  - Merkel cell carcinoma in organ-transplant recipients: report of two cases with
      unusual histological features and literature review.
AB  - BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ
      transplantation and are often associated with human papillomavirus (HPV). Merkel
      cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have
      been reported up till now, usually briefly, in organ transplant patients.
      METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one
      renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of
      post graft, respectively. These were studied histologically and
      immunohistochemically, as well as virologically for the presence of HPV. A
      thorough literature review of all reported cases of Merkel cell carcinoma
      following solid organ transplantation was performed. RESULTS: Despite a typical
      immunophenotype, the tumors showed unusual histological features: both were
      epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma.
      Search for HPV by immunohistochemistry and PCR proved negative in both cases.
      CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is
      much rarer than other non melanoma skin cancers but may show unusual histologic
      features. HPV do not seem to be involved in its pathogenesis.

PMID- 17026522
TI  - Nephrogenic fibrosing dermopathy and calciphylaxis with pseudoxanthoma elasticum
      like changes.
AB  - Nephrogenic fibrosing dermopathy (NFD) and calciphylaxis are rare conditions that
      are associated with chronic kidney disease. Histopathologic changes, including
      dystrophic dermal calcification, often in association with elastic fibers have
      been observed in NFD and calciphylaxis. A pattern of dermal elastic fiber
      calcification that mimics pseudoxanthoma elasticum (PXE) has been previously
      reported as an incidental finding in the setting of calciphylaxis. Despite a
      shared association with renal disease and abnormal calcium deposits, however, NFD
      and calciphylaxis are discrete pathologic processes with distinct clinical and
      histopathologic features. Criteria for each are reviewed through case
      presentation of a patient meeting the clinical and histopathologic criteria for
      both NFD and calciphylaxis with histologic features mimicking PXE.

PMID- 17026523
TI  - Reactivation of dormant cutaneous Leishmania infection in a kidney transplant
      patient.
AB  - BACKGROUND: Leishmaniasis is an infection caused by a protozoan parasite
      belonging to genus Leishmania and transmitted by the Phlebotomus sandfly.
      Clinical presentations of infection include visceral, cutaneous, and
      mucocutaneous forms. Leishmaniasis is endemic in Africa, Asia, Europe, South
      America, and southern part of North America. This infection is extremely rare in
      the US and is mostly found among travelers coming from endemic areas. Cases of
      cutaneous and visceral leishmaniasis have been reported in organ transplant
      recipients in endemic areas. CASE REPORT: We describe a case of cutaneous
      leishmaniasis in a kidney transplant patient, originally from Bolivia, who
      resides in the area known to be non-endemic for leishmaniasis and who is known
      not to travel within or outside of the US after the transplantation. RESULTS:
      Histologic examination of cutaneous lesion revealed extensive subcutaneous
      lymphohistiocytic inflammation with clusters of amastigote within histiocytes.
      CONCLUSION: To our knowledge, this is the first case of cutaneous leishmaniasis
      in a kidney transplant patient residing in the US in an area known to be non
      endemic for leishmaniasis, probably after reactivation of a previously dormant
      infection acquired outside of the US at least 9 months prior to developing
      clinical symptoms.

PMID- 17026524
TI  - Pigmented malignant hidroacanthoma simplex mimicking irritated seborrheic
      keratosis.
AB  - Pigmented variant of malignant hidroacanthoma simplex (PMHS) is very rare. We are
      aware of only two reported cases, all arising in pigmented hidroacanthoma simplex
      (HS). We report the third case of PMHS arising in a pigmented HS. A 71-year-old
      woman presented with a well-demarcated pigmented hyperkeratotic tumor on the
      right knee resembling irritated seborrheic keratosis. Histopathologic examination
      of the excised tumor revealed intraepidermal proliferation of atypical polygonal
      poroid cells forming large, sharply demarcated nests with colonization of
      dendritic melanocytes. In addition, there were focal changes of a benign
      pigmented HS and syringofibroadenoma. The key diagnostic features of ductal
      structures and intracytoplasmic lumina were highlighted by carcinoembryonic
      antigen and epithelial membrane antigen immunostaining. PMHS should be
      differentiated from irritated seborrheic keratosis, melanoacanthoma, Bowen's
      disease and malignant melanoma both clinically and pathologically.

PMID- 17026525
TI  - CD-34-reactive trichodiscoma.

PMID- 17026526
TI  - The dynamic pattern of glucocorticoid receptor-mediated transcriptional responses
      in neuronal PC12 cells.
AB  - The aim of the current study was (i) to examine the overlap in the pattern of
      glucocorticoid receptor (GR)-mediated transcriptional responses between different
      neuronal substrates and (ii) to assess the nature of these responses by
      differentiating between primary and downstream GR-responsive genes. For this
      purpose, nerve growth factor-differentiated catecholaminergic PC12 cells were
      used in which endogenous GRs were activated briefly with a high dose of
      corticosterone followed by gene expression profiling 1 and 3 h afterwards using
      Affymetrix GeneChips. The results revealed a strikingly similar temporal pattern
      to that which was reported previously in hippocampus, with only down-regulated
      genes 1 h after GR activation and the majority of genes up-regulated 3 h after GR
      activation. Real-time quantatitive PCR of transcripts in cycloheximide-treated
      cells showed that all five GR-responsive genes selected from the 1-h time point
      were primary responsive, whereas all four GR-responsive genes selected from the 3
      h time point were downstream responsive. At the level of individual genes, the
      overlap with the previously generated hippocampal data sets was small,
      illustrating the cell-type specifity of GR-mediated genomic responses. Finally,
      we identified a number of interesting genes, such as SWI/SNF, synaptosomal
      associated protein 25 and certain Rab proteins which may play a role in the
      effects of glucocorticoids on catecholaminergic neuronal functioning.

PMID- 17026527
TI  - Up-regulation of dopamine D(2)L mRNA levels in the ventral tegmental area and
      dorsal striatum of amphetamine-sensitized C57BL/6 mice: role of Ca(v)1.3 L-type
      Ca(2+) channels.
AB  - Dopamine D(2) long (D(2)L) and D(2) short (D(2)S) isoforms of the D(2) receptor
      play an important role in psychostimulant-induced neuronal adaptations. In this
      study, we used quantitative real-time PCR to specifically amplify these two
      splice variants to examine their mRNA expression in the dorsal striatum (dStr),
      nucleus accumbens (NAc) and the ventral tegmental area (VTA) of amphetamine
      sensitized C57BL/6 mice. We found a significant increase in D(2)L mRNA in the VTA
      and dStr of amphetamine-treated mice that positively correlated with the
      sensitized locomotor response. We also found a significant increase in D(2)S mRNA
      in the VTA. We further examined the role of the Ca(v)1.3 subtype of L-type Ca(2+)
      channels in up-regulation of D(2)L and D(2)S mRNA in the VTA. Amphetamine
      pretreated Ca(v)1.3 wild-type (Ca(v)1.3(+/+)) mice exhibited sensitized behavior
      and a significant increase in D(2)L and D(2)S mRNA compared with saline
      pretreated mice Amphetamine-pretreated homozygous Ca(v)1.3 knockout (Ca(v)1.3(-/
      )) mice did not exhibit sensitized behavior. There was a significant increase in
      D(2)S mRNA, but not D(2)L mRNA. In conclusion, our results find that amphetamine
      increases D(2)L mRNA expression in the dStr and the VTA, an adaptation that
      correlates with expression of sensitized behavior and dependence on Ca(v)1.3
      Ca(2+) channels.

PMID- 17026528
TI  - Manipulating Kv4.2 identifies a specific component of hippocampal pyramidal
      neuron A-current that depends upon Kv4.2 expression.
AB  - The somatodendritic A-current, I(SA), in hippocampal CA1 pyramidal neurons
      regulates the processing of synaptic inputs and the amplitude of back propagating
      action potentials into the dendritic tree, as well as the action potential firing
      properties at the soma. In this study, we have used RNA interference and over
      expression to show that expression of the Kv4.2 gene specifically regulates the
      I(SA) component of A-current in these neurons. In dissociated hippocampal
      pyramidal neuron cultures, or organotypic cultured CA1 pyramidal neurons, the
      expression level of Kv4.2 is such that the I(SA) channels are maintained in the
      population at a peak conductance of approximately 950 pS/pF. Suppression of Kv4.2
      transcripts in hippocampal pyramidal neurons using an RNA interference vector
      suppresses I(SA) current by 60% in 2 days, similar to the effect of expressing
      dominant-negative Kv4 channel constructs. Increasing the expression of Kv4.2 in
      these neurons increases the level of I(SA) to 170% of the normal set point
      without altering the biophysical properties. Our results establish a specific
      role for native Kv4.2 transcripts in forming and maintaining I(SA) current at
      characteristic levels in hippocampal pyramidal neurons.

PMID- 17026529
TI  - PACAP and C2-ceramide generate different AP-1 complexes through a MAP-kinase
      dependent pathway: involvement of c-Fos in PACAP-induced Bcl-2 expression.
AB  - The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)
      inhibits C2-ceramide-induced cell death through blockade of the mitochondrial
      apoptotic pathway in rat cerebellar granule neurones. However, the gene induction
      processes and transcription factors involved in the anti-apoptotic effect of
      PACAP remain unknown. Here, we show that PACAP and C2-ceramide activate activator
      protein-1 (AP-1) DNA binding in a dose- and time-dependent manner, but generate
      different AP-1 dimers. Thus, PACAP increased the proportion of c-Fos and Jun D
      while C2-ceramide increased c-Jun and reduced c-Fos in AP-1 complexes. In
      addition, PACAP strongly activated c-Fos gene expression while C2-ceramide
      markedly increased c-Jun phosphorylation. The effect of PACAP on c-Fos expression
      was blocked by the mitogen-activated protein kinase/extracellular signal
      regulated kinase (MEK) inhibitor, U0126, while phosphorylation of c-Jun induced
      by C2-ceramide was abrogated by the protein phosphatase 2A (PP2A) inhibitor,
      okadaic acid. Transfection of immature granule cells with c-Fos siRNA, which
      strongly reduced basal and PACAP-stimulated levels of the protein, totally
      prevented the stimulatory effect of PACAP on Bcl-2 expression. The present study
      demonstrates that AP-1 complexes containing c-Fos mediate the effect of PACAP on
      Bcl-2 gene expression in cerebellar granule neurones. Our data also indicate that
      different AP-1 dimers are associated with the pro-apoptotic effect of C2-ceramide
      and the anti-apoptotic effect of PACAP.

PMID- 17026530
TI  - Dorsal hippocampal administration of triiodothyronine enhances long-term memory
      for trace cued and delay contextual fear conditioning in rats.
AB  - Thyroid hormones play critical roles in brain maturation and cognitive functions.
      The present study investigated the role of thyroid hormone in emotional learning
      and memory using trace and delay contextual and cued fear conditioning tasks,
      respectively. Rats were administered triiodothyronine (T3) into the dorsal
      hippocampal area 10 min before training or immediately after training, and were
      scored for freezing behaviour in the same context and in a novel context with and
      without an auditory cue that had been paired previously with an aversive
      stimulus, a foot shock. Rats administered T3 before and after training both
      exhibited significantly increased long-term fear memory in the trace cued and the
      delay contextual fear conditioning procedures compared to their control groups.
      The T3-administered rats were not significantly different from their respective
      controls on the acquisition and short-term fear memory in the trace and delay
      fear conditioning tasks. No significant difference on long-term trace contextual
      and delay cued fear memory, respectively, was found. These results indicate that
      the observed T3-induced enhancement of long-term contextual and cued fear memory
      was specific to the hippocampus-dependent conditioning tasks. These findings are
      the first to demonstrate that infusion of T3 into the dorsal hippocampus can
      improve performance on an emotional memory task.

PMID- 17026531
TI  - Nerve growth factor secretion in cultured enteric glia cells is modulated by
      proinflammatory cytokines.
AB  - The enteric nervous system is composed of neurones and glial cells. These enteric
      glia cells (EGC) appear to be essential for the maintenance of gut homeostasis
      and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an
      important role for the gut integrity by regulating sensory and inflammatory
      processes in the intestines. Here, we demonstrate EGCs as one source of NGF and
      show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A
      (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and
      lipopolysaccharides. NGF is continuously secreted from cultured EGCs and
      proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this
      neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no
      effect on NGF expression. Furthermore, NGF secretion was sustained for more than
      12 h after withdrawal of the proinflammatory cytokines, suggesting the
      involvement of transcriptional and/or translational processes. Thus, the release
      of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a
      higher expression of TrkA in EGCs. NGF, in turn, can increase visceral
      sensitivity and, on the other hand, appears to improve gut inflammation.
      Therefore, NGF secreting EGCs may play a key role in modulating visceral
      sensitivity and might be involved in inflammatory processes of the gut.

PMID- 17026532
TI  - Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate
      release in the hippocampus of the near-term foetal guinea pig.
AB  - Exposure to high cortisol concentration can injure the developing brain, possibly
      via an excitotoxic mechanism involving glutamate (Glu). The present study tested
      the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal
      hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the
      foetal compartment and alters sensitivity to glucocorticoid-induced Glu release
      in the foetal hippocampus. Pregnant guinea pigs received daily oral
      administration of ethanol (4 g/kg maternal body weight/day) or isocaloric
      sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately
      GD 68) at which time they were euthanised, 1 h after their final treatment.
      Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined
      in foetal plasma. Basal and electrically stimulated Glu and gamma-aminobutyric
      acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective
      glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal
      slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N
      methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in
      situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE
      increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated
      glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices.
      Low DEX concentration (0.3 microM) decreased stimulated glutamate, but not GABA,
      release in both CPEE and control foetal hippocampal slices. High DEX
      concentration (3.0 microM) increased basal release of Glu, but not GABA, in CPEE
      foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the
      hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the
      CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE
      increases high glucocorticoid concentration-induced Glu release in the foetal
      hippocampus, presumably as a consequence of increased GR expression. These
      effects of CPEE, coupled with increased glutamate release and increased NMDA
      receptor expression, may predispose the near-term foetal hippocampus to GR and
      Glu-NMDA receptor-mediated neurodevelopmental toxicity.

PMID- 17026533
TI  - Lack of annexin 1 results in an increase in corticotroph number in male but not
      female mice.
AB  - Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium
      binding proteins with a well demonstrated role in early delayed (30 min to 3 h)
      inhibitory feedback of glucocorticoids in the pituitary. We have examined
      corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of
      lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1
      wild-type, heterozygote and null mice was fixed and examined (i) by confocal
      immunocytochemistry to determine the number of corticotrophs and (ii) by electron
      microscopy to examine the size, secretory granule population and secretory
      machinery of corticotrophs. No differences in these parameters were detected in
      female mice. In male ANXA1 null mice, there were approximately four-fold more
      corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null
      mice were smaller and had reduced numbers of secretory granules (the reduction in
      granules paralleled the reduction in cell size). No differences in the numerical
      density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were
      detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic
      hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but
      pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6
      pituitary content was significantly elevated in male and reduced in female ANXA1
      null mice compared to wild-type. In conclusion, these data indicate that ANXA1
      deficiency is associated with gender-specific changes in corticotroph number and
      structure, via direct actions of ANXA1 and/or indirect changes in factors such as
      IL-6.

PMID- 17026534
TI  - Oestrogen synthesis in the hippocampus: role in axon outgrowth.
AB  - Ovarian oestrogens have been postulated to be neuroprotective. It has also been
      shown that considerable amounts of oestrogens are synthesised in hippocampal
      neurones. In the present study, we focused on a potential role of hippocampus
      derived oestradiol compared to gonad-derived oestradiol on axon outgrowth of
      hippocampal neurones. To address the role of hippocampus-derived oestradiol, we
      inhibited oestrogen synthesis by treatment of neonatal hippocampal cell cultures
      with letrozole, a specific aromatase inhibitor. As an alternative, we used siRNA
      against steroidogenic acute regulatory protein (StAR). Axon outgrowth and GAP-43
      expression were significantly down-regulated in response to letrozole and in
      siRNA-StAR transfected cells. The effects after inhibition of oestrogen synthesis
      in response to letrozole and in siRNA-StAR transfected cells were reversed by
      oestrogen supplementation. No difference was found between ovariectomised
      animals, cycling animals at pro-oestrus and ovariectomised and subsequently
      oestradiol-treated animals. However, high pharmacological doses of oestradiol
      promoted axon outgrowth, which was possible to abolish by the oestrogen receptor
      antagonist ICI 182,780. Our results show that oestradiol-induced neurite
      outgrowth is very likely mediated by genomic oestrogen receptors and requires
      higher doses of oestradiol than physiological serum concentrations derived from
      the gonads.

PMID- 17026535
TI  - Sexual behaviour induces the expression of activity-regulated cytoskeletal
      protein and modifies neuronal morphology in the female rat ventromedial
      hypothalamus.
AB  - Female sexual behaviour activates a distributed network within the brain,
      including the ventrolateral subdivision of the hypothalamic ventromedial nucleus
      (vlVMH), as demonstrated by behavioural studies performed in conjunction with the
      neuroanatomical analysis of immediate early gene (IEG) expression. However, it
      has been difficult to interpret mating-induced IEG expression because the precise
      function of many IEGs remains poorly defined. One possible function for genomic
      activation of the vlVMH during mating behaviour is to establish synaptic
      remodelling. The present experiments tested the hypothesis that sexual behaviour
      rapidly induces the expression of a structural protein associated with synaptic
      plasticity and ultimately causes morphological changes in the vlVMH. First, the
      expression of activity-regulated cytoskeletal protein (Arc), an IEG associated
      with neural plasticity, was assayed immunohistochemically in females after
      approximately 1 h of mating. The number of Arc-labelled neurones in the vlVMH was
      greater in mated females compared to unmated controls. Second, VMH neurones were
      biolistically labelled for morphological measurements, including soma size,
      dendrite number and length and dendritic spine density. Dendritic spine density
      in the vlVMH was significantly reduced 5 days after mating in experienced females
      compared to sexually naive females. There were no differences between these
      groups in soma size, dendrite length or dendrite number. Collectively, these
      studies suggest that mating behaviour produces short-term changes in structural
      proteins and long-term, selective changes in dendrite morphology, which then may
      influence future behaviours and/or physiology.

PMID- 17026536
TI  - Metabolic signals modulate hypothalamic-pituitary-adrenal axis activation during
      maternal separation of the neonatal mouse.
AB  - The postnatal development of the mouse is characterised by a period of hypo
      responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to moderate
      stressors. Maternal separation disinhibits this blockade of the HPA axis, but the
      mechanism responsible is not clear. The present study examined the influence of
      metabolic signals on the central and peripheral components of the HPA axis in
      neonatal mice aged 8 days in absence or presence of the mother. Reductions in
      plasma glucose and leptin as well as rapid increases in plasma ghrelin were
      apparent in the neonate 4 h following maternal deprivation and maximal at 8 h. In
      addition, maternal separation induced an increase of neuropeptide Y (NPY) mRNA
      expression in the arcuate nucleus, a decrease of corticotrophin-releasing hormone
      (CRH) mRNA expression in the paraventricular nucleus and a rise in serum
      corticosterone. Pharmacological manipulation of the metabolic signals attenuated
      the HPA response to maternal separation. Thus, the rise in plasma corticosterone
      induced by maternal separation was ameliorated by prevention of reduction in
      blood glucose or blockade of the ghrelin signalling pathway, as were the
      hypothalamic changes in NPY and CRH mRNAs. By contrast, leptin treatment did not
      affect the HPA axis response to maternal separation. Together these results
      suggest that metabolic signals play an important role in triggering the HPA
      response of the neonate to maternal separation.

PMID- 17026537
TI  - Protective effects of endotoxin in a rat model of chronic inflammation are
      accompanied by suppressed secretion of pro-inflammatory cytokines and biphasic
      alteration in hypothalamo-pituitary-adrenal axis activity.
AB  - We have previously demonstrated that Gram-negative bacterial endotoxin can exert
      long-term protective effects against the chronic inflammatory disease adjuvant
      arthritis in rats. The present study was designed to investigate the mechanisms
      and time-course of hypothalamo-pituitary-adrenocortical (HPA) axis activity and
      cytokine secretion underlying this phenomenon. Rats were injected with endotoxin
      (lipopolysaccharide) and blood was collected either 7 or 21 days later. Priming
      with endotoxin induced a biphasic alteration in secretion of adrenocorticotrophic
      hormone and corticosterone in response to a second injection of endotoxin, with
      decreased secretion observed after 7 days whereas robust secretion was observed
      at 21 days. Seven days following priming with endotoxin, plasma concentrations of
      pro-inflammatory cytokines interleukin (IL)-6 and interferon (IFN)-gamma were
      reduced by 90%, and tumour necrosis factor (TNF)-alpha by 70%, compared to saline
      treated rats, whereas robust secretion of the anti-inflammatory cytokine IL-10
      was maintained in both groups. A similar net change favouring an anti
      inflammatory cytokine secretory milieu was also observed 21 days following
      priming with endotoxin. This study provides evidence that the long-term
      protective effects of endotoxin on inflammation are associated with a sustained
      reduction in secretion of pro-inflammatory cytokines. HPA axis hypoactivity at 7
      days suggests that corticosterone is not involved in suppressing IL-6, IFN-gamma
      and TNF-alpha at this time point. Conversely, hypersecretion of corticosterone at
      21 days may underlie synchronous suppression of IL-6 and IFN-gamma. These data
      provide novel insight into interactions between HPA axis activity and cytokine
      secretion following endotoxin priming prior to induction of inflammatory disease.

PMID- 17026538
TI  - Laser capture microdissection of plant cells from tape-transferred paraffin
      sections promotes recovery of structurally intact RNA for global gene profiling.
AB  - Laser capture microdissection and related technologies permit the harvest of
      individual cells and cell types. Isolation of either nucleic acids or proteins
      from laser-captured cells supports such downstream applications as the
      construction of cell-specific cDNA libraries and the profiling of expressed genes
      and proteins. The success of these endeavors is dependent upon the yield, purity
      and structural integrity of the macromolecules derived from harvested cells.
      Here, we report protocols that promote the isolation of structurally intact RNA
      from laser-captured cells of paraffin-embedded tissues. The use of a tape
      transfer system that obviates the need to wet paraffin sections prior to slide
      mounting significantly increases RNA structural quality. Integrity is assessed
      directly via electrophoretic separation of picogram-nanogram levels of total RNA
      isolated from multiple cell types, including those comprising Arabidopsis ovules,
      replums and stamen abscission zones. RNA prepared from specialized cells within
      siliques provided targets for profiling the Arabidopsis genome during replum cell
      development. Digital northern analysis of transcripts expressed near the
      threshold of the system's ability to score signal presence suggests that low
      abundance transcripts representing as little as approximately 0.002% of total
      mRNA can be reliably detected. Microarray data reveal a significant shift from
      primary cell-wall metabolism to lignin biosynthesis in replum tissues during
      fruit maturation.

PMID- 17026539
TI  - Additive contribution of AMT1;1 and AMT1;3 to high-affinity ammonium uptake
      across the plasma membrane of nitrogen-deficient Arabidopsis roots.
AB  - In Arabidopsis four root-expressed AMT genes encode functional ammonium
      transporters, which raises the question of their role in primary ammonium uptake.
      After pre-culturing under nitrogen-deficiency conditions, we quantified the
      influx of (15)N-labeled ammonium in T-DNA insertion lines and observed that the
      loss of either AMT1;1 or AMT1;3 led to a decrease in the high-affinity ammonium
      influx of approximately 30%. Under nitrogen-sufficient conditions the ammonium
      influx was lower in Columbia glabra compared with Wassilewskija (WS), and AMT1;1
      did not contribute significantly to the ammonium influx in Col-gl. Ectopic
      expression of AMT1;3 under the control of a 35S promoter in either of the
      insertion lines amt1;3-1 or amt1;1-1 increased the ammonium influx above the
      level of their corresponding wild types. In transgenic lines carrying AMT
      promoter-GFP constructs, the promoter activities of AMT1;1 and AMT1;3 were both
      upregulated under nitrogen-deficiency conditions and were localized to the
      rhizodermis, including root hairs. AMT gene-GFP fusions that were stably
      expressed under the control of their own promoters were localized to the plasma
      membrane. The double insertion line amt1;1-1amt1;3-1 showed a decreased
      sensitivity to the toxic ammonium analog methylammonium and a decrease in the
      ammonium influx of up to 70% relative to wild-type plants. These results suggest
      an additive contribution of AMT1;1 and AMT1;3 to the overall ammonium uptake
      capacity in Arabidopsis roots under nitrogen-deficiency conditions.

PMID- 17026540
TI  - An eIF4E allele confers resistance to an uncapped and non-polyadenylated RNA
      virus in melon.
AB  - The characterization of natural recessive resistance genes and virus-resistant
      mutants of Arabidopsis have implicated translation initiation factors of the 4E
      family [eIF4E and eIF(iso)4E] as susceptibility factors required for virus
      multiplication and resistance expression. To date, viruses controlled by these
      genes mainly belong to the family Potyviridae. Melon necrotic spot virus (MNSV)
      belongs to the family Tombusviridae (genus Carmovirus) and is an uncapped and non
      polyadenylated RNA virus. In melon, nsv-mediated resistance is a natural source
      of recessive resistance against all strains of MNSV except MNSV-264. Analyses of
      chimeras between non-resistance-breaking and resistance-breaking strains have
      shown that the avirulence determinant maps to the 3'-untranslated region (3'-UTR)
      of the viral genome. Using a combination of positional cloning and microsynteny
      analysis between Arabidopsis thaliana and melon, we genetically and physically
      delimited the nsv locus to a single bacterial artificial chromosome clone and
      identified the melon eukaryotic translation initiation factor 4E (Cm-eIF4E) as a
      candidate gene. Complementation analysis using a biolistic transient expression
      assay, confirmed Cm-eIF4E as the product of nsv. A single amino acid change at
      position 228 of the protein led to the resistance to MNSV. Protein expression and
      cap-binding analysis showed that Cm-eIF4E encoded by a resistant plant was not
      affected in it's cap-binding activity. The Agrobacterium-mediated transient
      expression of the susceptibility allele of Cm-eIF4E in Nicotiana benthamiana
      enhanced MNSV-264 accumulation. Based on these results, a model to explain melon
      resistance to MNSV is proposed. These data, and data from other authors, suggest
      that translation initiation factors of the eIF4E family are universal
      determinants of plant susceptibility to RNA viruses.

PMID- 17026541
TI  - Advances in equine surgery.

PMID- 17026542
TI  - Use of a synthetic bone substitute to retard molariform tooth drift after
      maxillary tooth loss in ponies.
AB  - OBJECTIVE: To evaluate the effect of alveolar bone substitute on post-extraction
      drift of maxillary cheek teeth in ponies. STUDY DESIGN: In vivo longitudinal
      experimental study. ANIMALS: Five ponies (5-7 years) with a healthy dentition.
      METHODS: Both maxillary 4th premolar teeth (Triadan 08) were surgically removed.
      One alveolus was filled with a biocompatible non-resorbable bone substitute
      (Bioplant 24), whereas the other healed by second intention. A polyvinylsiloxane
      plug and spring wire isolated the bone substitute from the oral environment.
      Pathologic changes to dentition and adjacent soft tissue were recorded. Tooth
      drift was calculated after 1 and 2 years. RESULTS: At 1 month, bone substitute
      material was incorporated into healthy tissue. Tooth drift was observed but
      differed significantly between control and treated sides at 2 years (P<.01). For
      both techniques, tooth drift differed significantly between years 1 and 2
      (P<.001). Total drift in control arcades for year 1 was 10.69+/-2.12 mm and for
      year 2 was 9.08+/-0.87 mm, whereas for bone substitute arcades it was 9.90+/-1.60
      mm for year 1 and 5.60+/-1.78 mm for year 2. CONCLUSIONS: Partial tooth
      replacement therapy after maxillary P4 extraction provided good healing in the
      immediate post-surgical phase. Alveolar filling with bone substitute material
      significantly slowed post-extraction tooth drift but did not stop it completely.
      Clinical Relevance- Important changes occur in equine dentition after maxillary
      cheek teeth removal. Further longer term observations are needed to fully
      validate study findings.

PMID- 17026543
TI  - Levator labii superioris muscle transposition to treat oromaxillary sinus fistula
      in three horses.
AB  - OBJECTIVE: To describe surgical transposition of the levator labii superioris
      muscle to treat oromaxillary sinus fistula in horses. STUDY DESIGN: Clinical
      study. ANIMALS: Three horses with chronic oromaxillary sinus fistula. METHODS:
      After severing its tendinous insertion, the muscle belly of the levator labii
      superioris muscle was retracted and transposed through the oromaxillary sinus
      fistula. The tendon exited the oral cavity through a full-thickness buccal
      incision created adjacent to the oral end of the fistula and was then tunneled
      subcutaneously in a ventral direction before being anchored by sutures to the
      cheek tissues. RESULTS: Fistulae healed with few complications and with good
      cosmetic and functional results. CONCLUSIONS: Oromaxillary sinus fistula
      associated with molariform tooth loss in horses can be treated successfully by
      transposition of the levator labii superioris muscle. CLINICAL RELEVANCE:
      Transposition of the levator labii superioris muscle should be considered for
      resolution of chronic oromaxillary sinus fistula in horses.

PMID- 17026544
TI  - Cell growth characteristics and differentiation frequency of adherent equine bone
      marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity.
AB  - OBJECTIVES: To characterize equine bone marrow (BM)-derived mesenchymal stem cell
      (MSC) growth characteristics and frequency as well as their adipogenic and
      osteogenic differentiation potential. STUDY DESIGN: In vitro experimental study.
      ANIMALS: Foals (n=3, age range, 17-51 days) and young horses (n=5, age range, 9
      months to 5 years). METHODS: Equine MSCs were harvested and isolated from sternal
      BM aspirates and grown up to passage 10 to determine cell-doubling (CD)
      characteristics. Limit dilution assays were performed on primary and passaged
      MSCs to determine the frequency of colony-forming units with a fibroblastic
      phenotype (CFU-F), and the frequency of MSC differentiation into adipocytes (CFU
      Ad) and osteoblasts (CFU-Ob). RESULTS: Initial MSC isolates had a lag phase with
      a significantly longer CD time (DT=4.9+/-1.6 days) compared with the average DT
      (1.4+/-0.22 days) of subsequent MSC passages. Approximately 1 in 4224+/-3265 of
      the total nucleated BM cells displayed fibroblast colony-forming activity.
      Primary MSCs differentiated in response to adipogenic and osteogenic inductive
      conditions and maintained their differentiation potential during subsequent
      passages. CONCLUSIONS: The frequency, in vitro growth rate, and adipogenic and
      osteogenic differentiation potential of foals and young adult horses are similar
      to those documented for BM MSCs of other mammalian species. CLINICAL RELEVANCE:
      The results have direct relevance to the use of BM as a potential source of adult
      stem cells for tissue engineering applications in equine veterinary medicine.

PMID- 17026545
TI  - Comparison of radiography and computed tomography to evaluate
      metacarpo/metatarsophalangeal joint pathology of paired limbs of thoroughbred
      racehorses with severe condylar fracture.
AB  - OBJECTIVE: To compare the orthogonal radiographic (OR) and computed tomographic
      (CT) appearance of paired Thoroughbred racehorse limbs with severe condylar
      fracture. STUDY DESIGN: In vitro study. SAMPLE POPULATION: Cadaveric paired limbs
      with severe condylar fracture (n=11 horses). METHODS: Four standard radiographic
      and multiple transverse CT images were obtained of the fractured and
      contralateral limbs centering on the metacarpo/metatarsophalangeal (fetlock)
      joints. Radiographs and CT images were graded by 4 raters, and interobserver
      agreement was calculated. Imaging evaluations were supplemented by fetlock joint
      dissection. A consensus description of actual injury and the detection accuracy
      of OR and CT for that injury was determined. Results- Rater agreement for OR and
      CT for most pathologic features was good or excellent. OR was similar to CT for
      the detection of condylar and diaphyseal third metacarpal and metatarsal (MC/MT3)
      fractures, diaphyseal fractures of the first phalanx (P1), and fracture location
      on the condyle. CT was superior to OR for detection of MC/MT3 proximal fissures
      and articular comminution, condylar small cracks and lucencies, and proximal
      sesamoid fractures. OR was superior to CT for detection of proximal P1 dorsal
      fractures. Both OR and CT were poor at detecting palmar/planter proximal P1
      fractures and coalescing cracks in the subchondral bone of MC/MT3. CONCLUSIONS:
      CT is better than OR for detection of pathology in limbs with condylar fractures,
      but does not detect every pathologic feature. CLINICAL RELEVANCE: CT provides
      superior information of pathology in Thoroughbred racehorses with condylar
      fractures.

PMID- 17026546
TI  - Computed tomographic documentation of a comminuted fourth carpal bone fracture
      associated with carpal instability treated by partial carpal arthrodesis in an
      Arabian filly.
AB  - OBJECTIVE: To report treatment of a unilateral comminuted fourth carpal bone (C4)
      fracture associated with carpal instability by partial carpal arthrodesis (PCA)
      of the middle carpal joint (MCJ) and carpometacarpal joint (CMCJ). STUDY DESIGN:
      Case Report. ANIMALS: An 8-month-old Arabian filly. METHODS: A C4 slab fracture
      was diagnosed radiographically; however, fracture comminution was conclusively
      diagnosed after computed tomographic (CT) imaging. PCA of the MCJ and CMCJ was
      performed with 2 narrow dynamic compression plates. RESULTS: PCA provided
      appropriate carpal stability and correct limb alignment immediately after
      surgery. Complete bony fusion with substantial carpal flexion and no lameness at
      walk or light trot was observed 8 months after surgery. CONCLUSIONS: Carpal CT
      was successfully used to define fracture configuration after standard
      radiographic examination failed to delineate comminution. PCA was selected
      because of joint instability and lateral carpal collapse of MCJ and CMCJ and can
      be successfully used to treat comminuted C4 slab fractures associated with carpal
      instability. Moderate MCJ osteoarthritis without radiocarpal joint involvement
      allows pain-free, substantial carpal flexion and thus, return to low-level
      pleasure riding may be possible. CLINICAL RELEVANCE: CT imaging may more
      adequately characterize traumatic carpal bone injury, particularly, when carpal
      bone fracture configuration cannot be determined on standard radiographs. Early
      PCA of the MCJ and CMCJ is an useful alternative to treat comminuted C4 slab
      fractures that cannot be reconstructed.

PMID- 17026547
TI  - Computer-assisted surgery for screw insertion into the distal sesamoid bone in
      horses: an in vitro study.
AB  - OBJECTIVE: To compare the precision of computer-assisted surgery with a
      conventional technique (CV) using a special guiding device for screw insertion
      into the distal sesamoid bone in horses. STUDY DESIGN: In vitro experimental
      study. SAMPLE POPULATION: Cadaveric forelimb specimens. METHODS: Insertion of a
      3.5 mm cortex screw in lag fashion along the longitudinal axis of intact (non
      fractured) distal sesamoid bones was evaluated in 2 groups (8 limbs each): CV and
      computer-assisted surgery (CAS). For CV, the screw was inserted using a special
      guiding device and fluoroscopy, whereas for CAS, the screw was inserted using
      computer-assisted navigation. The accuracy of screw placement was verified by
      radiography, computed tomography, and specimen dissection. RESULTS: Surgical
      precision was better in CAS compared with CV. CONCLUSION: CAS improves the
      accuracy of lateromedial screw insertion, in lag fashion, into the distal
      sesamoid bone. CLINICAL RELEVANCE: The CAS technique should be considered for
      improved accuracy of screw insertion in fractures of the distal sesamoid bone.

PMID- 17026548
TI  - An in vitro biomechanical comparison between prototype tapered shaft cortical
      bone screws and AO cortical bone screws for an equine metacarpal dynamic
      compression plate fixation of osteotomized equine third metacarpal bones.
AB  - OBJECTIVES: To compare biomechanical properties of a prototype 5.5 mm tapered
      shaft cortical screw (TSS) and 5.5 mm AO cortical screw for an equine third
      metacarpal dynamic compression plate (EM-DCP) fixation to repair osteotomized
      equine third metacarpal (MC3) bones. STUDY DESIGN: Paired in vitro biomechanical
      testing of cadaveric equine MC3 with a mid-diaphyseal osteotomy, stabilized by 1
      of 2 methods for fracture fixation. ANIMAL POPULATION: Adult equine cadaveric MC3
      bones (n=12 pairs). METHODS: Twelve pairs of equine MC3 were divided into 3
      groups (4 pairs each) for (1) 4-point bending single cycle to failure testing,
      (2) 4-point bending cyclic fatigue testing, and (3) torsional single cycle to
      failure testing. An EM-DCP (10-hole, 4.5 mm) was applied to the dorsal surface of
      each, mid-diaphyseal osteotomized, MC3 pair. For each MC3 bone pair, 1 was
      randomly chosen to have the EM-DCP secured with four 5.5 mm TSS (2 screws
      proximal and distal to the osteotomy; TSS construct), two 5.5 mm AO cortical
      screws (most proximal and distal holes in the plate) and four 4.5 mm AO cortical
      screws in the remaining holes. The control construct (AO construct) had four 5.5
      mm AO cortical screws to secure the EM-DCP in the 2 holes proximal and distal to
      the osteotomy in the contralateral bone from each pair. The remaining holes of
      the EM-DCP were filled with two 5.5 mm AO cortical screws (most proximal and
      distal holes in the plate) and four 4.5 mm AO cortical screws. All plates and
      screws were applied using standard AO/ASIF techniques. Mean test variable values
      for each method were compared using a paired t-test within each group.
      Significance was set at P<.05. RESULTS: Mean 4-point bending yield load, yield
      bending moment, bending composite rigidity, failure load and failure bending
      moment of the TSS construct were significantly greater (P<.00004 for yield and
      P<.00001 for failure loads) than those of the AO construct. Mean cycles to
      failure in 4-point bending of the TSS construct was significantly greater
      (P<.0002) than that of the AO construct. The mean yield load and composite
      rigidity in torsion of the TSS construct were significantly greater (P<.0039 and
      P<.00003, respectively) than that of the AO construct. CONCLUSION: The TSS
      construct provides increased stability in both static overload testing and cyclic
      fatigue testing. CLINICAL RELEVANCE: The results of this in vitro study support
      the conclusion that the EM-DCP fixation using the prototype 5.5 mm TSS is
      biomechanically superior to the EM-DCP fixation using 5.5 mm AO cortical screws
      for the stabilization of osteotomized equine MC3.

PMID- 17026549
TI  - A comparison of laryngoplasty and modified partial arytenoidectomy as treatments
      for laryngeal hemiplegia in exercising horses.
AB  - OBJECTIVE: To compare upper airway mechanics, arterial blood gases, and tracheal
      contamination in horses with induced left laryngeal hemiplegia (recurrent
      laryngeal neuropathy [RLN]) treated by laryngoplasty/vocal cordectomy (LPVC) or
      modified partial arytenoidectomy (MPA). STUDY DESIGN: Repeated measures under the
      following conditions: Control, RLN, LPVC, and MPA. ANIMALS: Six horses. METHODS:
      Two trials were conducted under all conditions at 80% and 100% of maximal heart
      rate (HR(max)). In Trial 1, arterial blood gases, tracheal and pharyngeal
      pressures, and laryngeal videoendoscopy were recorded. In Trial 2, upper airway
      pressure and airflow were determined. Tracheobronchial aspirates were performed
      after exercise to quantify airway contamination. RESULTS: Compared with control,
      RLN significantly increased inspiratory impedance and worsened exercise-induced
      hypoxemia. At 80% HR(max), LPVC restored most variables to control values. At
      100% HR(max), LPVC improved all variables, but did not restore minute volume,
      arterial pH, and PaCO(2). At 80% HR(max), MPA restored all variables except
      bicarbonate to control values. At 100% HR(max), MPA improved all variables, but
      did not statistically restore minute ventilation or bicarbonate level. Only minor
      differences were noted between LPVC and MPA. Both resulted in equivalent tracheal
      contamination. CONCLUSIONS: Airway mechanics and arterial blood gas values were
      not restored to normal after either LPVC or MPA in horses exercising at HR(max).
      This does not affect ventilation at sub-maximal exercise, but has clinical
      implications at HR(max). Both procedures diminish normal laryngeal protective
      mechanisms. CLINICAL RELEVANCE: At sub-maximal exercise intensities both LPVC and
      MPA restore airway ventilation to normal. At maximal exercise the superiority of
      LPVC over MPA is slight.

PMID- 17026550
TI  - Ventriculocordectomy as the sole treatment for recurrent laryngeal neuropathy:
      long-term results from ninety-two horses.
AB  - OBJECTIVE: To evaluate the effect ventriculocordectomy (VC) for treatment of
      recurrent laryngeal neuropathy (RLN) on exercise performance and owner
      satisfaction in a mixed-breed population of horses. STUDY DESIGN: Retrospective
      study. ANIMALS: Adult horses (n=92) with a history of abnormal respiratory noise
      and RLN. METHODS: Retrospective analysis of horse that had unilateral VC (and
      contralateral ventriculectomy in 63 horses) for treatment of idiopathic RLN.
      Owners/trainers completed a questionnaire about complications and outcome at
      least 1 year after surgery. Performance index was determined using race records
      for previously raced Thoroughbreds to evaluate outcome. RESULTS: Clinical signs
      included abnormal exercise-induced respiratory noises (noises; 52%), poor
      performance (11%), and noises and poor performance (37%). The median preoperative
      resting endoscopic grade of laryngeal function was Havemeyer grade III.1 (mild
      asymmetry). No discharge from the laryngotomy 1 week postoperatively occurred in
      62% horses, 22% coughed after surgery, 66% made no noises, 9% continued to make
      noises at the canter, 21% made noise at the gallop, and 4% of owners were unsure
      whether noises were present. Ninety-three percent of horses returned to full work
      after surgery. Overall, 86% of owners considered the surgery worthwhile, 3% did
      not consider it worthwhile, and 11% were unsure. Surgery had a significantly
      beneficial effect on the racing performance index in Thoroughbreds (P=.004).
      CONCLUSIONS: VC is a useful alternative to laryngoplasty for selected cases of
      RLN and is associated with a positive effect on exercise performance, a low
      postoperative complication rate, and a high rate of owner satisfaction. CLINICAL
      RELEVANCE: Unilateral VC should be considered as a sole treatment in horses with
      low grades of RLN.

PMID- 17026551
TI  - Standing surgical removal of inspissated guttural pouch exudate (chondroids) in
      ten horses.
AB  - OBJECTIVE: To report use of a modified Whitehouse approach in standing horses for
      management of inspissated guttural pouch empyema. STUDY DESIGN: Retrospective
      study. ANIMALS: Adult horses (n=10) with guttural pouch empyema. METHODS:
      Inspissated exudate in 1 or both guttural pouches was removed surgically through
      a modified Whitehouse approach, with the horses standing and sedated. Medical
      records of affected horses were reviewed to determine history; physical,
      endoscopic, and radiological examination findings; surgical technique;
      complications, and outcome. RESULTS: All horses had purulent nasal discharge; 3
      horses had dysphagia, 2 had recurrent laryngeal neuropathy on the side affected
      by guttural pouch empyema, and 1 had persistent soft palate displacement.
      Inspissated exudate was removed safely without causing apparent discomfort. Eight
      horses returned to their previous level of athletic activity after surgery; 1
      horse dysphagic before surgery, was euthanatized because of persistent dysphagia
      after surgery, and 1 horse died 1 week after surgery for unknown reasons.
      Streptococcus equi subsp equi was isolated from the affected guttural pouch of 3
      horses. CONCLUSIONS: Inspissated exudate can be removed surgically from the
      guttural pouch in standing horses through a modified Whitehouse approach.
      CLINICAL RELEVANCE: To eliminate risks associated with general anesthesia and
      avoid surgical suite contamination, removal of chondroids can be performed in
      standing sedated horses through a modified Whitehouse approach.

PMID- 17026552
TI  - Mandibular condylectomy and meniscectomy for the treatment of septic
      temporomandibular joint arthritis in a horse.
AB  - OBJECTIVE: To report use of mandibular condylectomy for treatment of advanced
      degenerative joint disease of the temporomandibular joint (TMJ) caused by sepsis.
      DESIGN: Clinical case report. ANIMALS: Two-year-old Noriker filly. METHODS:
      Computed tomography (CT) was used to confirm advanced degenerative joint disease
      of the left TMJ and for follow-up after mandibular condylectomy and removal of
      necrotic meniscus. RESULTS: Painful swelling (3 weeks duration) with drainage
      located just caudal to the left lateral canthus of the eye was associated with
      atrophy of the left masseter muscle, masticatory problems, and inappetence. There
      was incisor malocclusion with a 1.4 cm resting lateral mandibular deviation to
      the right and inability to open the mouth more than a few centimeters. Left
      mandibular condylectomy combined with meniscectomy and thorough debridement of
      the septic left TMJ resulted in resolution of clinical signs and complete return
      of function. Streptococcus zooepidemicus, intermediately resistant to penicillin
      and subsequently to enrofloxacin, was isolated from the wound. Regeneration of a
      mandibular "pseudocondyle" was evident on CT at 4 months. At 4 months and 1 year
      the filly had maximal mouth opening >10 cm and no malocclusion. CONCLUSION:
      Mandibular condylectomy can be used to facilitate management of septic TMJ
      arthritis. There was no radiologic or clinical evidence of TMJ ankylosis >1 year
      after meniscal removal. CLINICAL RELEVANCE: Mandibular condylectomy, including
      meniscectomy, is an acceptable treatment option for advanced TMJ septic arthritis
      and allowed return of normal masticatory function.

PMID- 17026553
TI  - Comparison of one-layer (continuous Lembert) versus two-layer (simple
      continuous/Cushing) hand-sewn end-to-end anastomosis in equine jejunum.
AB  - OBJECTIVE: To evaluate single and double layer end-to-end anastomosis in equine
      jejunum. STUDY DESIGN: Experimental in vitro study. ANIMALS: Mid-jejunal sections
      from 12 adult horses without gastrointestinal disease. METHODS: Jejunal end-to
      end anastomoses were performed by a continuous Lembert pattern or a simple
      continuous pattern oversewn with a Cushing pattern. Jejunal segments were
      distended with fluid at 1 L/min, and intraluminal pressure at failure, and mode
      of failure were recorded. Bursting pressure and bursting wall tension were
      calculated. Anastomosis construction time and degree of luminal reduction were
      recorded. Results- Single layer anastomoses were constructed in less time than 2
      layer anastomoses. Both anastomotic techniques resulted in luminal reduction
      compared with control tissue; however, the reduction was smaller with a 1-layer
      continuous Lembert anastomosis. No differences were noted in bursting pressure or
      bursting wall tension between groups. CONCLUSIONS: Anastomosis using a 1-layer
      continuous Lembert pattern resulted in a larger stoma, was faster to perform, and
      as strong as a 2-layer anastomosis. CLINICAL RELEVANCE: Use of a 1-layer
      continuous Lembert pattern for jejunojejunosotomy may be beneficial by decreasing
      anastomosis time and produce a larger stoma than a 2-layer anastomosis.

PMID- 17026554
TI  - Initial evaluation of a technique for complete cecal bypass in the horse.
AB  - OBJECTIVE: To describe a novel stapling technique for creation of a complete
      cecal bypass, without ileal transection in horses. STUDY DESIGN: Experimental
      study. ANIMALS: Four adult horses. METHODS: Through a ventral median celiotomy,
      jejunocolostomy was made with an intraluminal anastomosis device (ILA-100) and
      oversewn with a Cushing pattern to reinforce the staple line. Immediately distal
      to the anastomosis, 4 rows of staples were applied using a thoracoabdominal
      stapling device (TA-90) to occlude the lumen of the distal jejunum and proximal
      ileum. Necropsy exams were performed at least 60 days after surgery. RESULTS: No
      intraoperative complications occurred. Cecal bypass was functional in all horses
      at necropsy. The most oral staple line across the ileum partially failed in 1
      horse; however cecal bypass was functional. CONCLUSIONS: Complete cecal bypass
      without ileal transection is a viable alternative to traditional methods of
      complete cecal bypass. Two sets of staple lines across the ileum are recommended.
      Longer term follow-up is warranted before clinical use of this technique.
      CLINICAL RELEVANCE: Cecal bypass without ileal transection is technically simple
      and effectively bypasses the cecum. It also should intuitively require less time
      and have a reduced risk of contamination compared with complete cecal bypass with
      ileal transection.

PMID- 17026555
TI  - In vitro evaluation of an inverted end-to-end equine jejunojejunal anastomosis
      using skin staples.
AB  - OBJECTIVE: To compare functional indices of end-to-end (EEA) jejunojejunal
      anastomosis using skin staples in horses with a 2-layer inverting hand-sewn
      technique. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Jejunal segments
      from 8 fresh equine cadavers. METHODS: For each bowel segment, 2 EEA anastomoses
      were created: one 2-layer hand-sewn and one 1-layer using skin staples. Time for
      anastomosis creation was recorded and compared. Lumen diameter of each
      anastomosis was measured on digital radiographs after intraluminal instillation
      of contrast medium and inflation of the jejunal segments to 14 mm Hg. Anastomotic
      indices (a compensated measure of stoma diameter) and bursting pressure were
      determined. RESULTS: EEA jejunal anastomosis using skin staples was significantly
      faster than use of a 2-layer hand-sewn technique. Anastomotic index, a measure of
      lumen size, was significantly larger with the skin-staple technique; however, the
      bursting pressure of stapled anastomoses was significantly less than for the hand
      sewn technique, but the values were well above those reported for other
      anastomotic techniques. CONCLUSIONS: An anastomotic technique using skin staples
      was easy to learn and perform, effective and faster, and mechanically comparable
      with a hand-sewn 2-layer technique. CLINICAL RELEVANCE: The staple technique
      could be beneficial in equine gastrointestinal surgery by reducing anastomosis
      time, although further in vivo studies are needed to establish clinical safety.

PMID- 17026556
TI  - In vitro evaluation of a closed-bowel technique for one-layer hand-sewn inverting
      end-to-end jejunojejunosotomy in the horse.
AB  - OBJECTIVE: To report a technique for closed-bowel 1-layer inverting end-to-end
      jejunojejunal anastomosis in horses. STUDY DESIGN: Experimental study. SAMPLE
      POPULATION: Fresh cadaveric jejunal segments from 12 horses. METHODS: For each
      bowel segment a 1-layer closed and a 2-layer inverting end-to-end
      jejunojejunosotomy was created. Anastomosis construction time and anastomotic
      bursting pressure were measured and compared. RESULTS: Closed-bowel anastomosis
      was significantly faster to create than a 2-layer technique. Luminal narrowing
      (<30%) was similar with both techniques and comparable with other inverting
      techniques. Bursting pressure was significantly higher for the 2-layer technique,
      although all anastomoses resisted pressures higher than those reported for other
      jejunojejunal anastomosis techniques. CONCLUSIONS: A 1-layer hand-sewn, closed,
      inverting jejunojejunosotomy using a modified Doyen clamp was easy and faster to
      perform, and resulted in functional characteristics similar to, a 2-layer hand
      sewn inverting technique. CLINICAL RELEVANCE: A closed, 1-layer inverting
      technique could be considered for equine jejunal anastomosis but requires in vivo
      evaluation before recommendation for clinical use.

PMID- 17026557
TI  - Laparoscopic intestinal exploration and full-thickness intestinal biopsy in
      standing horses: a pilot study.
AB  - OBJECTIVE: To assess a laparoscopic technique for equine intestinal biopsy. STUDY
      DESIGN: Experimental study. ANIMALS: Seven adult horses. METHODS: Food but not
      water was withheld for 36 hours before laparoscopy. In 3 horses (group A)
      standing, right laparoscopic access to different small intestinal segments was
      compared with ventral median celiotomy access. Inaccessible segments were
      identified at necropsy. In 4 horses (group B), the feasibility of obtaining full
      thickness duodenal and cecal biopsies and any associated morbidity were
      evaluated. Biopsy specimens were collected during standing right laparoscopy
      using a 2-step procedure and intracorporeal suturing technique, and abdominal
      lavage was performed. Horses were monitored clinically and by abdominal fluid
      cytology and microbial culture, and repeat laparoscopy was performed on day 6.
      RESULTS: Standing right flank laparoscopy provided good observation of small
      intestinal segments and enabled manipulation of all but 15-20 cm of the duodenum
      and approximately 40 cm more ileum compared with ventral median celiotomy. Group
      B horses had no complications, no adhesions, and no bacterial growth from
      peritoneal fluid samples. None of the horses had signs of abdominal pain.
      CONCLUSION: A 2-stage intestinal biopsy technique performed during standing,
      right flank laparoscopy may be a safe alternative to exploratory celiotomy and
      biopsy in normal horses. CLINICAL RELEVANCE: Right flank laparoscopy allows
      biopsy of intestinal segments including duodenum and 50% more of the ileum than
      is accessible by ventral median celiotomy. This technique should be evaluated in
      clinical patients.

PMID- 17026558
TI  - Cytomegalovirus colitis complicating inflammatory bowel disease.
AB  - When patients with inflammatory bowel disease (IBD) are admitted to the hospital
      with a flare of acute severe colitis, the possibility of a concurrent
      cytomegalovirus (CMV) infection causing or worsening the colitis is often
      considered. IBD patients are usually immunosuppressed, and therefore presumably
      at increased risk for active CMV infection and disease. Multiple techniques are
      used to diagnose CMV infection, including endoscopy, histology, serology, viral
      culture, CMV antigen testing, and CMV DNA testing. Immunohistochemistry (IHC)
      performed on colon biopsy specimens with monoclonal antibodies directed against
      CMV immediate early antigen is considered by most to be the current gold standard
      for diagnosis. The prevalence of CMV infection in acute severe colitis appears to
      be 21-34%, and the prevalence of CMV infection in the steroid refractory subgroup
      of these patients is 33-36%. After antiviral therapy, colitis remission rates in
      IBD patients with CMV infection range from 67% to 100%, though CMV histological
      infection or the presence of circulating virus alone is not always associated
      with steroid resistance, and may not require antiviral therapy.

PMID- 17026559
TI  - The impact of colon preparation timing on colonoscopic detection of colorectal
      neoplasms--a prospective endoscopist-blinded randomized trial.
AB  - OBJECTIVES: Timing of colon preparation might influence the cleansing condition
      of the colon and therefore affect the quality and diagnostic yield of
      colonoscopy. This study compared two different timings of colon preparation to
      assess the efficacy of colon cleansing and diagnostic yield of colorectal
      neoplasms during colonoscopy. METHODS: One hundred twenty-one eligible subjects
      who had colorectal neoplasms detected at a screening colonoscopy were randomly
      assigned to receive colon preparation with polyethylene glycol electrolyte lavage
      solution (PEG-ELS) either on the day of (on the day group) or the night before
      (previous night group) a second colonoscopy. The condition of colon preparation
      and the diagnostic yield of colorectal neoplasms were recorded and compared
      between the two groups for the initial and second colonoscopies. RESULTS: Fifty
      nine subjects received colon preparation on the night before and 60 subjects
      received colon preparation the day of a second colonoscopy. Colon preparation for
      the second colonoscopy was better in the on-the-day group than in the previous
      night group (P= 0.003). Colon preparation for the second colonoscopy was better
      for each group in comparison with the initial colonoscopy (P < 0.0001). An
      interobserver variability analysis using 20 randomly selected colonoscopies from
      the two groups revealed good correlation among four colonoscopists. More lesions
      were detected in group A during the second colonoscopy (P= 0.028). CONCLUSION:
      Colon preparation on the day of colonoscopy has a better cleansing quality and
      higher diagnostic yield. Subjects who had lesions detected during the initial
      screening colonoscopy had better colon cleansing for the second colonoscopy
      regardless of the timing of preparation.

PMID- 17026560
TI  - A prospective, randomized comparison of adrenaline injection in combination with
      detachable snare versus adrenaline injection alone in the prevention of
      postpolypectomy bleeding in large colonic polyps.
AB  - OBJECTIVES: Our study sought to compare the efficacy of adrenaline injection in
      combination with detachable snare versus adrenaline injection alone in the
      prevention of postpolypectomy bleeding in large colonic polyps. METHODS: At the
      time of colonoscopy, patients with at least one colonic polyp > or =2 cm were
      randomized to receive treatment either by the injection of a 1:10.000 solution of
      adrenaline and the position of a detachable snare followed by a conventional
      snare polypectomy (group A) or injection of adrenaline followed by a conventional
      snare polypectomy (group B). A total of 159 consecutive patients were randomly
      assigned to one of the above groups. Out of them, 84 patients (47 men, 37 women,
      mean age 61 yr) were assigned to group A and 75 (37 men, 38 women, mean age 64
      yr) to group B. Early (<24 h) and late (>24 h-30 days) bleeding complications
      were assessed. RESULTS: Overall bleeding complications occurred in 10/159 (6.2%)
      of the patients. There were two cases of bleeding in group A (2.3%), and eight in
      group B (10.6%) (P= 0.04). The number of early bleeding episodes was
      significantly reduced in group A patients (1 case) compared to that of group B (7
      cases) (P= 0.02). In contrast, there was no significant difference between group
      A and B as far as late bleeding is concerned. CONCLUSIONS: Our data suggest that
      the use of adrenaline injection in combination with detachable snare may
      significantly decrease the number of early postpolypectomy bleeding episodes in
      patients with large colonic polyps.

PMID- 17026561
TI  - Incidence and management of primary malignant small bowel cancers: a well-defined
      French population study.
AB  - BACKGROUND AND AIM: Few data are available from population-based statistics on
      small bowel cancers. The aim of this study was to report on their incidence and
      management. METHODS: Data were obtained from the population-based Digestive
      Cancer Registry of Burgundy over a 26-yr period. Incidence rates were calculated
      by gender, age group, histological type, and 5-yr period. Treatment and stage at
      diagnosis were investigated. Prognosis was determined using crude and relative
      survival rates. A multivariate relative survival analysis was performed. RESULTS:
      Age-standardized incidence rates were 1.2/100,000 inhabitants for men and
      0.8/100,000 inhabitants for women. The mean 5-yr variation in incidence were,
      respectively, +46.7% (P < 0.01) and + 53.2% (P < 0.05). There were four main
      histological types: adenocarcinoma (40.4%), malignant endocrine tumors (30.5%),
      lymphoma (20.1%), and sarcoma (9.0%). Resection for cure was performed in 56.6%
      of the cases. Cancer was not extending beyond the organ in 33.2% of the cases,
      was associated with lymph node metastasis in 32.1%, and with distant metastasis
      or unresectability in 34.7%. The 5-yr relative survival rate was 37.4%. It varied
      between 56.8% for endocrine tumors and 17.8% for sarcoma. In the multivariate
      analysis, age, histology, and stage at diagnosis significantly influenced the
      prognosis. CONCLUSIONS: Small bowel cancers represent a heterogeneous group of
      rare tumors. Prognosis at a population level is worse than in hospital series. In
      the short term, new therapeutic possibilities represent the best way to improve
      prognosis.

PMID- 17026562
TI  - Agreement between rapid onsite and final cytologic interpretations of EUS-guided
      FNA specimens: implications for the endosonographer and patient management.
AB  - BACKGROUND: The practice of onsite cytology interpretation varies across
      endoscopic ultrasound (EUS) programs in the United States and Europe. The value,
      reliability, and agreement of rapid onsite evaluation (ROSE) compared with final
      interpretation and its impact on patient management remain largely unknown. We
      compared agreement between ROSE of EUS-FNA (endoscopic ultrasound-guided fine
      needle aspiration) specimens with final cytology interpretation and their
      respective operating characteristics. METHODS: We prospectively evaluated
      consecutive EUS-FNA specimens obtained by a single endosonographer in the
      presence of an attending cytopathologist (July 2000-November 2002). The
      "agreement" between ROSE and final cytology interpretation was assessed by the
      "kappa" statistic. The frequency and possible reasons for discrepancy between
      ROSE and final cytologic interpretation were determined. RESULTS: A total of 540
      patients (median age 63 yr, 77% white) underwent EUS-FNAs of 656 lesions. These
      included lymph nodes (LNs, N = 248), solid pancreatic masses (SPMs, N = 229),
      cystic pancreatic masses (CPM, N = 57), mural lesions (41), bile duct/gallbladder
      (N = 28), liver (N = 17), mediastinum/lung (N = 17), adrenal (N = 15), spleen (N
      = 3), and kidney (N = 1). Data were available for onsite evaluation in 607
      lesions. Initial cytology was benign (N = 243), atypical (N = 23), suspicious
      (24), malignant (300), and indeterminate (N = 17). Out of the 243 benign lesions
      interpreted by onsite evaluation, five lesions (2.1%) were upgraded to be
      malignant or suspicious for malignancy on final cytology report. Of the 300
      lesions initially reported malignant on ROSE, 294 (98%) remained malignant on the
      final cytology. There was an excellent agreement between ROSE and final cytologic
      evaluation (kappa = 84.0%, 95% CI 80.2-87.7), Compared with the true final
      status, accuracy for final interpretation was slightly higher than for ROSE but
      was not statistically significant (95.8%vs 93.9%). Scant cellularity remained the
      most frequent reason for discrepancy, accounting for 21 of 51 discrepancies
      (41%). Other reasons for discrepancy included: cases requiring an
      intradepartmental consultation (22%), cases requiring ancillary studies (12%),
      intra-observer variability (10%), and challenging diagnosis (10%). In three
      cases, (6%) we were unable to determine the possible reason for discrepancy.
      CONCLUSION: ROSE of EUS-FNA specimens is highly accurate compared with final
      cytologic evaluation. Because the diagnosis of malignancy rarely changes,
      informing our patients and their families and our referring physicians of a
      cancer diagnosis significantly reduces physician work load and expedites patient
      management. The majority of discrepancies are related to the nature of the lesion
      either because it sheds few cells, has challenging morphology, and/or requires
      additional ancillary studies.

PMID- 17026563
TI  - Microsatellite instability accounts for tumor site-related differences in
      clinicopathologic variables and prognosis in human colon cancers.
AB  - OBJECTIVE: Colon cancers with high frequency microsatellite instability (MSI-H)
      are preferentially located in the proximal colon. Given that 15-20% of sporadic
      colon cancers are MSI-H, we determined whether tumor site-specific differences in
      clinicopathological variables, biomarkers, and prognosis are due to inclusion of
      MSI-H cases. METHODS: TNM stage II and III primary colon carcinomas (N = 528)
      from patients enrolled in 5-fluorouracil-based adjuvant trials were analyzed for
      MSI using 11 microsatellite markers. Immunostaining for DNA mismatch repair
      (hMLH1, hMSH2, hMSH6) and p53 proteins was performed. DNA ploidy (diploid vs
      aneuploid/tetraploid) and proliferative indices (PI: S-phase + G(2)M) were
      analyzed by flow cytometry. RESULTS: MSI-H was found in 95 (18%) colon cancers.
      Proximal tumors (N = 286) were associated with MSI-H, older age (>65 yr), poor
      differentiation, and diploid DNA content compared with distal tumors (all P< or =
      0.016). Nuclear p53 staining was more frequent in distal tumors (P= 0.002); PI
      was unrelated to tumor site. When MSI-H tumors were excluded, no tumor site
      related differences were found except for age, which remained associated with
      proximal cancers (P= 0.030). Proximal site was associated with improved disease
      free survival in all patients (P= 0.042), but not when MSI-H cases were excluded
      (P= 0.236). MSI-H status or loss of mismatch repair proteins, diploidy, and lower
      PI were associated with improved survival rates. CONCLUSIONS: Tumor site-related
      differences in clinicopathological variables, biomarkers, and prognosis of
      sporadic colon cancers can be explained by the inclusion of MSI-H cases. Older
      age, however, is associated with proximal tumor site independent of MSI status.

PMID- 17026564
TI  - Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine
      in inflammatory bowel disease: long-term follow-up study of 394 patients.
AB  - AIM: To prospectively evaluate whether a relationship between thiopurine
      methyltransferase (TPMT) activity and incidence of adverse effects (especially
      myelotoxicity) exists, in a long-term follow-up study of a large group of
      patients with inflammatory bowel disease treated with azathioprine. METHODS: TPMT
      activity in red blood cells (RBC) was measured by a radiochemical method in 394
      consecutive patients with Crohn's disease (238) or ulcerative colitis (156)
      starting treatment with azathioprine. The relationship among several variables
      and TPMT values was assessed, and the correlation between such levels and the
      incidence of adverse effects was evaluated. RESULTS: Mean TPMT value was 18.6 +/-
      4 U/mL RBCs (range 9.4-33.7). No patient had low levels (<5), 7.1% had
      intermediate levels (5-13.7), and 92.9% had high levels (>13.8). Differences (P <
      0.001) were demonstrated in TPMT activity depending on the type of inflammatory
      bowel disease, but not on the remaining variables (including treatment with 5
      aminosalycilates). Adverse effects were reported in 74 patients (18.8%), the most
      frequent being gastrointestinal intolerance (9.1%) and myelotoxicity (4.3%). No
      patient having adverse effects had low TPMT levels. However, mean TPMT activity
      was lower in those with adverse effects (16.6 +/- 3 vs 19.1 +/- 4 U/mL, P <
      0.001). Moreover, the probability of suffering myelotoxicity in the high TPMT
      group was only 3.5%, compared with 14.3% in the TPMT intermediate group (95% CI =
      1.37-14.9; OR = 4.5). CONCLUSIONS: The strategy of determining TPMT activity in
      all patients prior to initiating treatment with azathioprine could help to
      minimize the risk of myelotoxicity, as patients with intermediate TPMT activity
      had fourfold more risk than high TPMT activity patients.

PMID- 17026565
TI  - Singapore familial adenomatous polyposis (FAP) patients with classical
      adenomatous polyposis but undetectable APC mutations have accelerated cancer
      progression.
AB  - OBJECTIVES: Germline mutation in adenomatous polyposis coli (APC) is detected in
      up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this
      study, we evaluated clinical features and APC mutations of Singapore FAP patients
      and contrasted genotype-phenotype correlation with Caucasians from other regions
      of the world and between FAP patients with and without detectable APC mutations.
      METHODS: We screened 242 members from 57 unrelated FAP families using a
      combination of cDNA protein truncation test, multiplex ligation-dependent probe
      amplification, and differential expression techniques. RESULTS: APC germline
      mutations were detected in 50 families. In contrast to Caucasians, fundic gland
      polyposis in Singapore patients was associated with APC mutations throughout the
      coding region and osteomas were also not confined to codon 767-1573. There was
      also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative
      patients from four families with mixed (adenomatous/hyperplastic/atypical
      juvenile) polyps were subsequently reclassified as hereditary mixed polyposis
      syndrome (HMPS) patients. APC mutation-negative patients with classical
      adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations.
      These patients had a significantly older age at diagnosis (P < 0.001) and more
      colorectal cancers (P= 0.017) than patients with APC mutations. CONCLUSIONS: We
      achieved a 94% (50/53) APC mutation detection rate via a combination of
      techniques, suggesting that the current detection rate is probably not
      exhaustive. Singapore patients have some features similar to and other features
      distinct from Caucasians. Furthermore, APC mutation-negative patients have
      accelerated cancer progression that merits closer surveillance.

PMID- 17026566
TI  - Association between liver fibrosis and insulin sensitivity in chronic hepatitis C
      patients.
AB  - BACKGROUND: Several clinical studies have suggested a possible link between
      chronic hepatitis caused by hepatitis C virus (HCV) and the development of
      diabetes mellitus. We investigated the association between liver fibrosis and
      glucose intolerance in HCV-infected patients by measuring insulin sensitivity and
      beta-cell function. METHOD: A total of 83 chronic HCV-infected patients were
      recruited into this study. We evaluated insulin sensitivity and beta-cell
      function of all patients in a fasting state (homeostasis model assessment of
      insulin resistance [HOMA-R] and homeostasis model assessment of beta-cell
      function [HOMA-beta]) and after an oral load of 75 g glucose (whole-body insulin
      sensitivity index [WBISI] and Delta-insulin/Delta-glucose 30). RESULTS: In a
      multivariate analysis, severe fibrosis was the only independent factor associated
      with insulin resistance. There were significant differences in both HOMA-R (P=
      0.0063) and WBISI (P= 0.0159) between patients with mild fibrosis (N = 34) and
      those with severe fibrosis (N = 49). Although HOMA-beta was increased
      significantly in the subjects with severe fibrosis compared with those with mild
      fibrosis (P= 0.0169), Delta-insulin/Delta-glucose 30 showed no significant
      difference in stage of liver fibrosis, suggesting an uncertain association
      between liver fibrosis and beta-cell function. CONCLUSION: Our findings suggest
      that the development of liver fibrosis is associated with insulin resistance in
      HCV-infected patients.

PMID- 17026567
TI  - Gut-brain neuropeptides in the regulation of ingestive behaviors and obesity.
AB  - The prevalence of obesity has increased to epidemic proportions and has become an
      urgent public health problem. Obesity causes significant morbidity and mortality
      and its impact on health-care costs in the United States is growing dramatically.
      Apart from bariatric surgery treatment, options are limited. Future advances in
      treatment will rely on a better understanding of the pathogenesis and physiology
      of obesity. Alterations in gastrointestinal (GI) sensory-motor function and
      symptoms have been associated with obesity. GI neuroendocrine communications
      between the periphery and the brain regulate energy balance and ingestive
      behaviors. These interactions are largely mediated by the gut-brain peptides
      through negative and positive feedback loops that maintain energy homeostasis.
      Bariatric surgery has been shown effective, but the mechanisms of weight loss
      following these procedures clearly require further studies and a better
      understanding of the affects of bariatric surgery on the gut-brain neuropeptide
      homeostasis. Gut-brain peptides may provide attractive therapeutic targets in the
      fight against this very morbid disease. We review alterations in GI function and
      some of the more important gut-brain neuropeptides that occur in obesity.

PMID- 17026568
TI  - Influence of body position and stool characteristics on defecation in humans.
AB  - BACKGROUND: Whether defecation is influenced by body position or stool
      characteristics is unclear. AIM: We investigated effects of body position,
      presence of stool-like sensation, and stool form on defecation patterns and
      manometric profiles. METHODS: Rectal and anal pressures were assessed in 25
      healthy volunteers during attempted defecation either in the lying or sitting
      positions and with balloon-filled or empty rectum. Subjects also expelled a water
      filled (50 cc) balloon or silicone-stool (FECOM) either lying or sitting and
      rated their stooling sensation. RESULTS: When attempting to defecate in the lying
      position, a dyssynergic pattern was seen in 36% of subjects with empty rectum and
      24% with distended rectum. When sitting, 20% showed dyssynergia with empty rectum
      and 8% with distended rectum. More subjects (p < 0.05) showed dyssynergia in
      lying position. When lying, 60% could not expel balloon and 44% FECOM. When
      sitting, fewer (p < 0.05) failed to expel balloon (16%) or FECOM (4%). FECOM
      expulsion time was quicker (p < 0.02). Stool-like sensation was more commonly (p
      < 0.005) evoked by FECOM than balloon. CONCLUSIONS: In the lying position, one
      third showed dyssynergia and one-half could not expel artificial stool. Whereas
      when sitting with distended rectum, most showed normal defecation pattern and
      ability to expel stool. Thus, body position, sensation of stooling and stool
      characteristics may each influence defecation. Defecation is best evaluated in
      the sitting position with artificial stool.

PMID- 17026569
TI  - 30-day mortality after peptic ulcer perforation among users of newer selective
      COX-2 inhibitors and traditional NSAIDs: a population-based study.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drug (NSAID) use is a strong risk
      factor for peptic ulcer perforation, yet little is known about the outcome of
      this condition among NSAID users. We examined 30-day mortality after peptic ulcer
      perforation associated with the use of traditional NSAIDs and newer selective
      cyclo-oxygenase-2 (COX-2) inhibitors. METHODS: We conducted a cohort study of
      patients with the first hospitalization for peptic ulcer perforation, identified
      in discharge registries of three Danish counties between 1991 and 2003. Data on
      preadmission NSAID use, other ulcer-related drugs, and comorbidity were likewise
      from population-based registries. Mortality was ascertained from the Civil
      Registration System. We compared 30-day mortality in NSAID users and nonusers
      while adjusting for age, gender, comorbidity, previous uncomplicated peptic
      ulcer, and ulcer medication use. RESULTS: Of the 2,061 patients hospitalized with
      peptic ulcer perforation, 38% were current NSAID users. The 30-day mortality was
      25% overall, and 35% among current NSAID users. Compared with never-use, the
      adjusted 30-day mortality rate ratios (MRRs) were 1.8 (95% CI 1.4-2.3) for
      current use of NSAIDs alone and 1.6 (95% CI 1.2-2.2) for current use combined
      with other ulcer-associated drugs. The mortality increase associated with the use
      of COX-2 inhibitors was similar to that of traditional NSAIDs: adjusted MRR for
      users of COX-2 inhibitors alone and in combination, 2.0 (1.3-3.1) and 1.4 (0.8
      2.5), and for users of traditional NSAIDs alone or in combination, 1.7 (1.3-2.3)
      and 1.6 (1.2-2.3). CONCLUSION: Current use of NSAIDs, including COX-2 inhibitors,
      is associated with a poor prognosis for patients hospitalized with peptic ulcer
      perforation.

PMID- 17026570
TI  - Rapid development of diffuse large B-Cell lymphoma after successful eradication
      of Helicobacter pylori for gastric MALT lymphoma.
AB  - Primary low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the
      stomach has a potential to transform to high-grade diffuse large B-cell lymphoma
      (DLBCL). However, the clonal relation between MALT lymphoma and de novo DLBCL is
      still controversial. We report here three patients with Helicobacter pylori (H.
      pylori)-positive gastric MALT lymphoma rapidly progressing to DLBCL at the same
      site after successful eradication of H. pylori. Although MALT lymphomas in our
      cases did not possess t(11; 18)(q21;q21), sequence analysis of the rearranged
      immunoglobulin heavy chain gene showed no clonal relation between preceding MALT
      lymphoma cells and de novo DLBCL cells at the same site. These findings question
      the scenario of direct clonal progression of low-grade MALT lymphomas without
      t(11; 18)(q21;q21) to DLBCL and serve as a reminder of the risk of the
      progression of DLBCL with a distinct clonality immediately after H. pylori
      eradication for low-grade MALT lymphoma.

PMID- 17026572
TI  - Complexity of anti-immunosenescence strategies in humans.
AB  - Immunosenescence is characterized by three main aspects: (i) the shrinkage of the
      T cell repertoire and the accumulation of oligoclonal expansions (megaclones) of
      memory/effector cells directed toward ubiquitary infectious agents; (ii) the
      involution of the thymus and the exhaustion of naive T cells; and (iii) a chronic
      inflammatory status called inflamm-aging. We present here possible strategies to
      counteract these main aspects of immunosenescence in humans with particular
      attention to the reduction of antigenic load by pathogens, such as CMV, and the
      normalization of intestinal microflora, the possible utilization of IL-7 to
      reverse thymic involution, the purging of megaclones, the forced expression of
      CD28 on T lymphocytes, the reduction of inflamm-aging and the administration of
      nutrients such as vitamin D. Possible drawbacks of all these strategies are
      discussed. Finally, the complexity of a rejuvenation approach is stressed, with
      particular attention to the inhibitory role played by the "old microenvironment"
      on the performance of progenitor cells, the best candidate to counteract the
      decline in regenerative potential characteristic of organs and tissues from old
      organisms.

PMID- 17026573
TI  - Reversibility of the differentiated state: regeneration in amphibians.
AB  - In contrast to mammals, some fish and amphibians have retained the ability to
      regenerate complex body structures or organs, such as the limb, tail, eye lens,
      or even parts of the heart. One major difference in the response to injury is the
      appearance of a mesenchymal growth zone or blastema in these regenerative species
      instead of the scarring seen in mammals. This blastema is thought to largely
      derive from the dedifferentiation of various functional cell types, such as
      skeletal muscle, dermis, and cartilage. In the case of multinucleated skeletal
      muscle fibers, cell cycle reentry into S-phase as well as fragmentation into
      mononucleated progenitors is observed both in vitro and in vivo.

PMID- 17026574
TI  - The stairway: a novel behavioral test detecting sensomotoric stroke deficits in
      rats.
AB  - New therapeutic concepts of cell and tissue replacement therapies have been
      introduced in treatment of neurological disorders which require robust and
      sensitive sensomotoric behavioral diagnostic test systems for experimental
      research. However, most test arrays available are either expensive and/or
      sensitive to environmental disturbances. Moreover, an extensive training phase
      for experimental animals is often required by conventional tests to get
      reproducible data. In this study, we describe a new test array, the Stairway,
      that is robust, cost-effective, and needs only a minimum training phase. Its
      efficiency is evaluated in comparison to the well-established RotaRod and
      modified neurological severity score. Stroke was induced by middle cerebral
      artery occlusion. Human umbilical cord blood transplantation (n = 18) was
      performed 24 h after stroke by intravenous injection of suspended cells in
      comparison to control injections (n = 18), while behavioral assessment was
      carried out continuously for 29 days. Furthermore, development of lesions was
      monitored by magnetic resonance imaging. The results reveal the Stairway test as
      a simple, highly reproducible, and easy manageable test system thus reflecting
      therapeutic benefits precisely.

PMID- 17026575
TI  - Poly(ether imide) scaffolds as multifunctional materials for potential
      applications in regenerative medicine.
AB  - This article gives an overview of scaffolds that can be prepared from poly(ether
      imide) (PEI). These scaffolds were developed for extracorporeal blood
      detoxification processes in which specific compounds from blood or plasma are
      removed selectively. Both the preparation of porous microparticles and the
      preparation of hollow fibers are described. Commercially available particulate
      support materials have the disadvantage of a low accessibility of the internal
      pore system, a poor flow-through behavior and low adsorption specificity. Thus,
      novel support materials with optimally adapted properties profiles are needed.
      The second part of this article shows some recently developed highly asymmetric
      PEI hollow fibers. PEI scaffolds can be considered multifunctional because they
      combine separation characteristics, biocompatibility, sufficient biostability,
      and the possibility of creating tailor-made biofunctional surfaces.

PMID- 17026576
TI  - Bone engineering: combining smart biomaterials and the application of stem cells.
AB  - Remarkable preclinical progress and achievements in the isolation and
      characterization of stem cells from different sources have been made, together
      with the ability to control proliferation and differentiation in vitro.
      Researchers and physicians pin their hope on stem cells to develop novel
      approaches in regenerative medicine. Stem cell therapy is no longer a scientific
      discipline in the laboratory or in animal models only, as it is already performed
      routinely in the human therapeutical and clinical treatment for hematological
      malignancies and clinical trials for bone repair. It has further been recognized
      that angiogenesis plays a pivotal role for the successful transplantation of in
      vitro engineered tissues like bone structures, for the repair of large bone
      defects to facilitate engraftment. We intended to generate transplantable
      composite grafts, which consist of in vitro generated bone tissue from
      multipotent adult progenitor cells, maintaining an angiogenic potential to ease
      and optimize a successful engraftment of long-term sustainable and viable bone
      tissue. The other component was generated from several synthetically produced
      three-dimensional tissues like fibrin, thrombin, collagen, hydroxyapatite, and
      beta-tricalciumphosphate in different compositions and concentrations, all
      mimicking natural body structures of bone tissue as biocompatible grafts. We
      established an in vitro mouse model, using bone marrow and peripheral blood
      derived murine progenitor cells as well as industrially manufactured materials
      generating composite grafts. Based on our preliminary results, we propose to
      pursue research on composite grafts for an extended graft survival and successful
      engraftment of transplanted tissue.

PMID- 17026577
TI  - Initiation of mesenchymal condensation in alginate hollow spheres--a useful model
      for understanding cartilage repair?
AB  - A promising strategy for the regeneration of degenerated cartilage tissue
      structure in osteoarthritic joints is the use of mesenchymal precursor cells.
      These cells can be triggered to undergo differentiation into functional active
      chondrocytes resulting in newly synthesized cartilage. Because chondrogenic
      differentiation is initiated by the step of mesenchymal condensation in vitro, it
      is of great interest to fully characterize the first lineage specific step in
      vitro. Therefore, a modified culture system was developed which mimics the
      process in vitro and may finally help to identify the key factors that are
      essential for the induction of chondrogenic differentiation in vivo. Compared to
      other established 3D culture systems like alginate beads and micromass cultures,
      the use of alginate hollow spheres bears the advantage to analyze different
      phases of cell aggregation starting from a single cell suspension of previously
      isolated and expanded human primary cells of mesenchymal origin.

PMID- 17026578
TI  - Electrospinning approaches toward scaffold engineering--a brief overview.
AB  - Tissue engineering involves the in vitro seeding of cells onto scaffolds which
      assume the role of supporting cell adhesion, migration, proliferation, and
      differentiation, and which define the three-dimensional shape of the tissue to be
      engineered. Among the various types of scaffold architectures available,
      scaffolds based on nanofibers mimicking to a certain extent the structure of the
      extracellular matrix offer great advantages. Electrospinning is the technique of
      choice for the preparation of such scaffolds. Investigations have revealed that
      the nanofibrous structure promotes cell adhesion, proliferation, and
      differentiation. Parameters relevant for these processes such as fiber diameters,
      surface topology, porosity, mechanical properties, and the fibrous architecture
      of the scaffold can be controlled by electrospinning in a broad range.

PMID- 17026579
TI  - Membrane bioreactor for cell tissues and organoids.
AB  - Progresses in polymeric membrane preparation and in the understanding and control
      of their transport properties make possible the design of novel membranes to be
      used for cell culture (e.g., hepatocytes, lymphocytes, pancreatic islets) in
      biohybrid systems such as therapeutic device or as in vitro model systems for
      studying the effects of various drugs and chemicals on cell metabolism. Special
      attention is paid to the design of the membrane with defined microstructure and
      physicochemical properties as well as to the importance of transport and
      physicochemical properties of the membrane in contact with the cells. The
      development of new biomaterials and bioreactors able to activate a specific
      response of the cells and to maintain cell differentiation for a long time is one
      of the most pertinent issues in the field of tissue engineering and regenerative
      medicine. Polymeric membranes are attractive for their selectivity and
      biostability characteristics in the use of biohybrid systems for cell culture.
      Semipermeable membranes act as a support for the adhesion of anchorage-dependent
      cells and allow the specific transport of metabolites and nutrients to cells and
      the removal of catabolites and specific products. Moreover, new membrane systems
      that have been recently realized as the membrane contactors might also
      potentially contribute to regenerative medicine and tissue engineering.

PMID- 17026580
TI  - A human lymph node in vitro--challenges and progress.
AB  - Extracorporeal human lymphatic organs are expected to be excellent tools in the
      study of human molecular and cellular bases of the immunologic balance and tissue
      harmony. A rational approach and process to design a device and a procedure to
      recreate the human lymph node environment in vitro is described with emphasis on
      T-cell activation. Based on this approach, a bioreactor and a process supporting
      self-assembly of human lymphatic tissues due to proper emulation of human
      architecture and homeostasis could be developed.

PMID- 17026581
TI  - The cardiovascular tissue-reactor: a novel device for the engineering of heart
      valves.
AB  - The shortage of human donor valves and disadvantages of current mechanical and
      xenogenic valve grafts cause a growing demand for biologically engineered valves.
      We developed a bioreactor for in vitro transformation of porcine semilunar heart
      valves into human valves. The reactor design was optimized in order to achieve a
      complete removal of porcine cells by trypsinization and cellularization of the
      remaining matrix with human vascular cells. The physical parameters of the
      reactor were characterized. Based on these data, decellularization and
      cellularization protocols were developed and the successful application of
      protocols was investigated by immunohistochemistry. The resulting reactor
      consisted of two connectable and perfuseable modules. Heart valve structures of
      varying sizes could be mounted into the reactor and could be completely
      depopulated within 4 days by a sequence of enzymatic and mechanical treatments
      applied simultaneously to the valves. Complete cellularization with human cells
      could be achieved after optimizing the seeding design, density, and time.

PMID- 17026582
TI  - Evaluation of liver support systems for preclinical testing by animal trials.
AB  - In the present review, various animal models of acute liver failure are reviewed
      with respect to their suitability for evaluating liver support systems (LSS)
      according to envisaged modes of therapy. In order to increase the value of the
      preclinical testing of LSS, it would be advantageous to include more than one
      animal model in the evaluation program. It is possible to identify appropriate
      sets of models, which make a suitable test system for particular clinical
      applications. A standardization of evaluation methods between testing groups
      would also be beneficial to the field of liver support.

PMID- 17026583
TI  - Visions for regenerative medicine: interface between scientific fact and science
      fiction.
AB  - This article gives a brief overview of the authors' views on the future
      development of tissue engineering with respect to the challenges both to the
      materials and life sciences. Emphasis will be placed on the advantages of three
      dimensional bioresorbable polymers in combination with relevant molecular cues
      and the application of autologous stem or progenitor cells. There is a
      requirement for much more diversity in the synthesis of so-called "intelligent"
      materials, which respond to external stimuli, as well as the development of novel
      drug and gene delivery systems. In addition, much more basic research is
      necessary in developmental biology and the application of modern cell and
      molecular biology to biomaterial questions.

PMID- 17026584
TI  - Future of regenerative medicine: challenges and hurdles.
AB  - Tissue regeneration strategies such as tissue engineering, growth factor
      administration, and stem cell-based therapies have undergone significant
      development over the past two decades. Most notably, we are much closer to
      realizing the engineering of whole organs and tissue with complex architecture
      than we were 5 years ago. A major driving force has been the demand placed by the
      scientific community at large and the public to go beyond simple engineering of
      tissues and demonstrate functionality in engineered tissues and functional
      recovery upon transplantation. Some recent advances include de novo engineering
      of bone, engineering of fully functional bladder, and vascularization of skeletal
      muscle constructs. Notwithstanding, several challenges lie ahead in making
      regenerative medicine a viable science of the future, the key being the evolution
      of programs and policies that promote a close relationship among government
      agencies, private sector, and academia, more specifically between materials
      scientists, biologists, and clinicians.

PMID- 17026586
TI  - The clinical features of anterior prostate cancers.
AB  - OBJECTIVE: To identify the clinical characteristics of anterior prostate cancers
      (APCs) and to compare these with posterior prostate cancers (PPCs). PATIENTS AND
      METHODS: We reviewed 1290 consecutive open and laparoscopic radical
      prostatectomies (RPs) at the authors' institution from January 2000 to March
      2004. Prostates were processed using a whole-mount technique. Each surgical
      specimen was reviewed by one pathologist, and tumour areas were marked, measured
      and mapped. Positive surgical margins (PSMs) were defined as the presence of
      cancer cells at the inked surface of the specimen. Specimens were then
      categorized by the location of their dominant tumour, i.e. pure anterior,
      anterior > posterior, posterior > anterior, or pure posterior. We compared the
      clinical and pathological characteristics of 259 patients in the pure-anterior
      group with the 594 in the pure-posterior group. RESULTS: Before RP, APCs had a
      significantly lower biopsy Gleason score (78% vs 68% with Gleason 4-6), fewer
      mean biopsy cores positive (2.0 vs 2.6), a smaller median percentage of positive
      cores (17% vs 26%), lower clinical stage (T1 in 79% vs 62%), and higher
      progression-free probability estimated by preoperative nomogram (86% vs 84%) than
      PPCs. Patients with APCs also had more previous negative biopsy sessions. The
      pathological analysis of RP specimens showed that those with APCs had higher
      tumour volume (1.6 vs 0.83 mL) and had a higher PSM rate (12% vs 7%) than those
      with PPCs, despite specimens with PPCs having higher rates of extraprostatic
      extension (10% vs 19%). CONCLUSIONS: APCs have lower Gleason grade and lower
      rates of extraprostatic extension, yet patients with anterior tumours have higher
      overall tumour volumes and higher PSM rates. Because current tools for detecting
      and staging prostate cancer can underestimate the extent of anterior prostate
      disease, improved methods are needed for localizing and characterizing anterior
      cancers.

PMID- 17026587
TI  - Sialorphin (the mature peptide product of Vcsa1) relaxes corporal smooth muscle
      tissue and increases erectile function in the ageing rat.
AB  - OBJECTIVE: To determine if the mature peptide product of the Vcsa1 gene,
      sialorphin, could restore erectile function in ageing rats, and whether these
      effects are mediated through relaxation of corporal smooth muscle tissue, as we
      recently reported that Vcsa1 is one of the most down-regulated genes in the
      corpora of rats in three distinct models of erectile dysfunction, and gene
      transfer of plasmids expressing Vcsa1 into the corpora of ageing rats restored
      erectile function. MATERIALS AND METHODS: Sialorphin was injected
      intracorporeally into retired breeder rats, and the effect on the physiology of
      corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement
      at different times after injection. In organ-bath studies, the ability of
      sialorphin (1 microg/mL) to enhance C-type natriuretic peptide (CNP) relaxation
      of corporal smooth muscle tissue strips was investigated after pre-contraction
      with 1 microm phenylephrine. RESULTS: Intracorporal injection of 100 microg
      sialorphin into retired breeder rats resulted in a time-dependent increase in the
      ICP/BP response to electrostimulation of the cavernosal nerve. After 55-65 min
      the ICP/BP ratio increased to approximately 0.6, a value associated with normal
      erectile function. In organ-bath studies after pre-contraction with 1 microm
      phenylephrine, 1 microm CNP significantly (67%) increased the relaxation rate of
      corporal tissue. This rate of relaxation was increased by 2.5-fold after
      incubation with sialorphin (1 microg/mL) compared with carrier alone. CONCLUSION:
      These results show that sialorphin has a role in erectile function, probably
      through a mechanism that involves relaxation of corporal smooth muscle tissue.

PMID- 17026588
TI  - The role of anticholinergics in men with lower urinary tract symptoms suggestive
      of benign prostatic hyperplasia: a systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the safety and efficacy of anticholinergics in men with
      lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia
      (BPH) by a systematic review of published reports and a meta-analysis of the
      reported outcomes. METHODS: We searched Medline, Embase and Cochrane databases
      (1966-2006), and hand-searched relevant reference lists and conference
      proceedings, for studies on the use of anticholinergics in men with BPH or
      bladder outlet obstruction. Eligible studies were assessed for quality and
      foreign language studies were translated. We collected data on all reported
      outcomes, conducted meta- analyses on the maximum urinary flow rate (Q(max)),
      postvoid residual urine volume (PVR) and volume at first contraction, and
      calculated the acute urinary retention (AUR) rate. We used sensitivity analysis
      to confirm the findings. RESULTS: We identified five randomized controlled trials
      (RCTs) and 15 observational studies. Four RCTs incorporating 633 patients were
      included in the meta-analyses. Anticholinergics did not significantly alter
      Q(max) (0.1 mL/s, 95% confidence interval, CI, 0.6-0.7). The PVR was increased by
      11.6 mL (95% CI 4.5-18.6) although there was no significant difference between
      AUR rates. The total International Prostate Symptom Scores (IPSS) were not
      significantly different, but there were improvements for IPSS storage subscores
      in one RCT. The AUR rate was 0.3% at the 12-week follow-up in 365 men in the RCTs
      and observational studies. CONCLUSION: Anticholinergic use in men with LUTS
      suggestive of BPH appears to be safe. Further studies are required to establish
      efficacy with a suitable precision.

PMID- 17026589
TI  - Simultaneous transurethral cystolithotripsy with holmium laser enucleation of the
      prostate: a prospective feasibility study and review of literature.
AB  - OBJECTIVE: To report experience with holmium laser enucleation of the prostate
      (HoLEP) simultaneously with transurethral holmium laser cystolithotripsy (HLC)
      for managing bladder outlet obstruction (BOO) and associated vesical calculi; we
      also review previously reported cases of managing vesical calculi and associated
      BOO. PATIENTS AND METHODS: The high-powered holmium laser is a very efficient
      multifunctional endourological instrument that effectively fragments calculi of
      all compositions and is capable of haemostatic cutting of tissue, resulting in
      minimal bleeding after prostatic resection. A prospective study was conducted
      from April 2003 that included 32 men who underwent simultaneous HoLEP with
      transurethral HLC at our institution. Demographic, laboratory, peri-operative and
      follow-up data were analysed. Complications during and after surgery were
      identified to assess the morbidity of procedure. RESULTS: The mean (range) size
      of bladder calculi was 34.6 (12-70) mm and the preoperative weight of the
      prostate was 51.9 (11-172) g. Combined HoLEP with transurethral HLC was
      technically feasible in all patients, and all were stone-free after surgery. The
      mean operative duration was 97.7 (40-230) min, the weight of prostate tissue
      removed 34.6 (5-88) g, and the duration of catheterization and hospital stay 29.3
      h and 34.8 h, respectively. Complications during and after surgery occurred in
      12.5% and 15.6% of patients, respectively; all complication were minor and none
      caused any residual disability to the patient. No patient required a blood
      transfusion or developed clot retention. CONCLUSIONS: Managing bladder stones and
      BOO with simultaneous transurethral HLC and HoLEP should be considered the
      treatment of choice for such cases. Stones of any size and composition, and
      prostates of practically any size can be treated endoscopically using the holmium
      laser, with acceptable morbidity once the technique is mastered. The review of
      previous reports suggested a need for a prospective study comparing endoscopic
      management of BOO and associated bladder stones, with medical management of BOO
      and extracorporeal shock wave lithotripsy/endoscopic lithotripsy for bladder
      stone.

PMID- 17026590
TI  - Ureteric embolization with stainless-steel coils for managing refractory lower
      urinary tract fistula: a 12-year experience.
AB  - OBJECTIVE: To report our 12-year experience with radiological treatment (ureteric
      embolization) for refractory urinary fistula, as malignancy, radiation therapy,
      and/or chronic inflammation increase the risk of lower urinary tract fistula
      after surgical urinary diversion, which can lead to significant morbidity, and
      for patients who are not surgical candidates permanent nephrostomy drainage and
      ureteric embolization offer an alternative form of urinary diversion. PATIENTS
      AND METHODS: We retrospectively reviewed patients who had ureteric occlusion for
      refractory urinary fistula at our institution between 1993 and 2005. Stainless
      steel coils, with or without gelatine sponge, were placed antegradely through a
      percutaneous nephrostomy tract. Patients were then managed by long-term
      nephrostomy drainage until death or definitive reconstructive surgery. RESULTS:
      In all, 29 patients (23 women and six men; mean age 59 years, sd 16) were
      identified who had urinary fistulae that were refractory to nephrostomy drainage
      alone. One patient had a history of severe perineal trauma and the remaining 28
      had a history of cancer. Seventeen fistulae occurred in the setting of previous
      surgery, 20 patients had received adjunctive pelvic irradiation and 11 had had
      chemotherapy. In all, 52 ureters were embolized; occlusion was successful in all
      cases, with complete or near-complete (<1 pad/day) dryness within 3 days. No
      repeat embolization was required and there were no significant complications. Two
      patients were lost to follow-up. Three patients had definitive urinary diversion
      surgery and currently are well. One patient is alive and living with nephrostomy
      tubes; 23 patients have died. CONCLUSION: Ureteric embolization is a viable
      option for managing complex lower urinary tract fistulae in patients with a poor
      performance status. It can be used as definitive management in patients with a
      limited life-expectancy or as a temporary measure in those for whom another
      management plan is anticipated.

PMID- 17026591
TI  - The association between T-type Ca2+ current and outward current in isolated human
      detrusor cells from stable and overactive bladders.
AB  - OBJECTIVE: To determine if bladder overactivity in humans is associated with an
      altered activity of Ca(2+) channels in detrusor smooth muscle and the consequent
      activation of other ion channels. MATERIAL AND METHODS: Samples of bladder were
      obtained from patients with urodynamically stable bladders, or with idiopathic
      detrusor overactivity. Isolated cells were patch-clamped with pipettes containing
      a Cs(+)-based filling solution to isolate inward currents, or a K(+)-filling
      solution to measure outward current. Components of inward current were separated
      according to their sensitivity to NiCl(2) (< or =100 microm) and nifedipine.
      RESULTS: Ni(2+)-sensitive (T-type) and nifedipine-sensitive (L-type) current was
      recorded in all cells. The voltage- and time-dependent properties were similar in
      cells from both patient groups. However, the current density of the L-type
      current was less, and that of the T-type current was greater, in myocytes from
      overactive bladders. In cells from overactive bladders, the mean K(+) current
      over the range - 80 to - 50 mV was also higher than in control cells. This
      current was sensitive to the large-conductance channel modulator iberiotoxin and
      to NiCl(2) (100 microm) CONCLUSIONS: Detrusor myocytes from overactive human
      bladders have a higher T-type Ca(2+) current density; we propose that this
      increases transient outward currents, and so might contribute to higher levels of
      spontaneous activity.

PMID- 17026592
TI  - The value of frozen-section analysis of ureteric margins on surgical decision
      making in patients undergoing radical cystectomy for bladder cancer.
AB  - OBJECTIVE: To prospectively investigate the value of routine frozen-section
      analysis (FSA) of the ureteric margin for detecting distal ureteric malignancy in
      patients undergoing cystectomy for bladder transitional cell carcinoma (TCC).
      PATIENTS AND METHODS: In all, 100 consecutive patients had a radical cystectomy
      for TCC of the bladder; routine FS biopsies were obtained from the lower ureters
      of all. Definitive pathology with step-sectioning of the lower ureters was
      reviewed, and the results of paraffin-wax embedded sections and FSA were
      compared. The true incidence of distal ureteric malignancy was identified and
      correlated with different clinical and pathological variables. RESULTS: There
      were 193 ureteric specimens examined; 16 ureters (8.3%) in 14 patients showed
      evidence of malignancy by FSA. True distal ureteric malignancy was diagnosed in
      29 ureteric specimens (15%) in 24 patients. The sensitivity and specificity of
      the FSA were 45% and 98%, respectively, while the positive and negative
      predictive values were 81% and 91%, respectively. There was no significant
      correlation between distal ureteric malignancy and: patient age, tumour site or
      morphology, clinical or pathological staging, ipsilateral hydronephrosis,
      suspicious intraoperative ureter, biopsy or tumour grade, associated carcinoma in
      situ or nodal involvement. Male gender and positive intraoperative FSA were the
      only predictors significantly associated with distal ureteric malignancy by
      univariate analysis (P = 0.01 and <0.01, respectively). Both predictors remained
      significant on multivariate analysis. CONCLUSION: A positive ureteric FSA during
      cystectomy has a high predictive value in the diagnosis of distal ureteric
      malignancy, and is justified as an independent predictor in male patients with
      bladder TCC.

PMID- 17026593
TI  - The effects of a new selective beta3-adrenoceptor agonist (GW427353) on
      spontaneous activity and detrusor relaxation in human bladder.
AB  - OBJECTIVE: To examine the effects of a new selective beta3-adrenoceptor agonist,
      GW427353 on human detrusor function, as beta2- and beta3-adrenoceptors have been
      identified in the bladder, and can mediate detrusor relaxation, but beta3
      adrenoceptors are less widely distributed and beta3-adrenoceptor agonists should
      have the therapeutic advantage of producing fewer treatment side-effects.
      PATIENTS AND METHODS: 'Normal' human detrusor was retrieved from 12 patients
      (mean age 56 years) at cystectomy and from organ donors. Detrusor strips (4 x 1 x
      1 mm) were mounted in superfused organ baths. Tone was induced with carbachol (5
      x 10(-7)m) before applying either a nonselective beta-adrenoceptor agonist
      (isoprenaline) or GW427353 (with or without the beta3-adrenoceptor antagonist,
      SR59230A). In addition, the effect of GW427353 was tested on intrinsic nerve
      evoked smooth muscle contraction over time. Effects on spontaneous activity were
      also recorded. RESULTS: GW427353 produced significant relaxation at
      concentrations of >10(-7)m; isoprenaline produced a significant effect from 10(
      6)m, but otherwise both agonists had similar effects. The addition of SR59230A
      (10(-7)m), produced partial inhibition of the GW427353 response. GW427353 at 10(
      6)m significantly reduced spontaneous activity within 10 min of incubation, and
      at higher concentrations (>5 x 10(-6)m) inhibited detrusor contractions evoked by
      electrical field stimulation. CONCLUSION: Neuropathic bladder dysfunction is
      characterized by increased spontaneous activity and involuntary detrusor
      contractions, which can result in urinary frequency, urgency, nocturia and
      incontinence. The novel feature of GW427353 is the ability to suppress
      spontaneous activity and produce significant relaxation in human detrusor tissue
      at low concentrations, whilst also inhibiting evoked detrusor contractions at
      higher concentrations.

PMID- 17026594
TI  - A clinical assessment of the performance of a sensor to detect crystalline
      biofilm formation on indwelling bladder catheters.
AB  - OBJECTIVES: To test the ability of a sensor developed to signal infection by the
      organisms that generate the crystalline biofilms that encrust catheters, to give
      an early warning that encrustation was occurring on patients' catheters, as the
      care of many patients undergoing long-term bladder catheterization is complicated
      by the encrustation and blockage of their catheters. PATIENTS AND METHODS: Twenty
      patients were followed prospectively for the lifetime of one of their catheters.
      Sensors based on cellulose acetate/bromothymol blue were placed in the urine
      collection bags, which were changed as usual at weekly intervals. The
      bacteriology was assessed and pH determined weekly on urine samples. Photographic
      records were made of the sensors twice weekly. On removal, each catheter was
      examined for encrustation and blockage. RESULTS: Proteus mirabilis was not
      isolated from five patients and in these cases the sensor colour remained golden
      yellow to brown. The catheters drained for the scheduled period and showed no
      signs of encrustation. By contrast, the sensors turned dark blue/black in the
      urine of all 15 patients infected with P. mirabilis. All these patients'
      catheters were encrusted and in 12 the catheters blocked. The mean interval
      between the sensor signalling and the catheter blocking was 12 days. CONCLUSION:
      The cellulose acetate/bromothymol blue sensors placed in the urine collection
      bags are capable of signalling infection by P. mirabilis. They also signal the
      early stages of catheter encrustation and allow catheter replacement in ample
      time to avoid the clinical crises and emergency referrals caused by catheter
      blockage.

PMID- 17026595
TI  - Clinically significant prostate cancer found incidentally in radical
      cystoprostatectomy specimens.
AB  - OBJECTIVE: To review the incidence, histopathological features and clinical
      outcomes of patients with incidental prostate cancer found in radical
      cystoprostatectomy (RCP) specimens excised for bladder cancer, to determine if
      these cancers affected the follow-up strategy and if prostate-sparing cystectomy
      would be appropriate for these patients. PATIENTS AND METHODS: We retrospectively
      reviewed the charts of men who had a RCP for transitional cell carcinoma (TCC) of
      the bladder, at our institution between 1987 and 2003. Patients with a
      preoperative diagnosis or clinical suspicion of prostate cancer were excluded
      from further analysis. We identified those men with incidental prostate cancer in
      the RCP specimens. The patients' demographic, histopathological and clinical
      outcome data were collected. RESULTS: In all, 217 men had RCP for TCC between
      1987 and 2003; 13 were excluded from the study due to a preoperative diagnosis or
      clinical suspicion of prostate cancer, and 58 (28%) were found to have incidental
      prostate cancer. The mean (range) follow-up was 47 (6-157) months. Of these
      prostate cancers, 20% were of Gleason score > or = 7 and two patients developed
      local and metastatic prostate cancer recurrences. CONCLUSION: Incidental prostate
      cancer is a relatively common finding in RCP specimens, with a significant
      proportion having the characteristics of clinically relevant prostate cancer. The
      follow-up for prostate cancer should be incorporated with that for TCC and
      adapted according to the grade and stage of the prostate cancer. Preserving the
      prostate in an attempt to decrease the morbidity after RCP carries a high risk of
      significant prostate cancer in the residual prostatic tissue, suggesting that
      prostate-sparing cystectomy should only be reserved for a highly selected group
      of patients.

PMID- 17026596
TI  - Retroperitoneal anomalies in men with testicular germ cell tumours.
AB  - OBJECTIVES: To assess whether vascular and other retroperitoneal anomalies are
      more frequent during retroperitoneal lymph node dissection (RPLND) for metastatic
      testicular tumours (when retroperitoneal masses persist after chemotherapy) than
      would be expected, based on the initial observations from one centre with a large
      experience of RPLND in the UK. PATIENTS AND METHODS: A prospective series of 278
      consecutive patients treated with RPLND for testicular tumours comprised the
      sample population. For each patient the presence or absence of four factors from
      the history was recorded. Each patient then underwent RPLND. During surgery, a
      template was constructed of the anatomy of the retroperitoneum and the
      information stored. Eight different retroperitoneal anatomical anomalies were
      identified in the sample population; the incidence of each was then compared with
      the largest available study of a normal population, and differences analysed
      statistically. RESULTS: Of the 278 patients who had RPLND, 55 had 59 anomalies
      (21%), found by history and as retroperitoneal vascular and urological anomalies;
      cryptorchidism was present in 7.6%, 9.5 times the incidence in the control
      population (P < 0.01). A left-sided inferior vena cava was present in 3.6% of
      patients, 21 times the incidence in the control population (P < 0.001); a retro
      aortic left renal vein in 3.2%, four times that in the control population (P <
      0.05); and ipsilateral renal agenesis had an incidence of 1% in the test
      population, 11 times greater than in the control population (P < 0.01).
      CONCLUSIONS: This prospective study of 278 RPLNDs provides evidence that some
      retroperitoneal anatomical anomalies are associated with testicular germ cell
      tumours. The link between maldescent and testicular tumours, rather than an
      isolated association, should be considered as part of a spectrum of
      retroperitoneal anomalies that occur in these men.

PMID- 17026597
TI  - The prevalence and predictors of erectile dysfunction in men with newly diagnosed
      with type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine the prevalence of and risk factors for erectile
      dysfunction (ED) in men newly diagnosed with type 2 diabetes mellitus (DM).
      PATIENTS AND METHODS: All consecutive samples of men newly diagnosed with type 2
      DM attending the diabetes centre in the capital of Kuwait were included in the
      study. Face-to-face interviews with the men were conducted using the
      International Index of Erectile Function (IIEF)-5 questionnaire. A threshold IIEF
      5 score of <21 was used to identify men with ED. Pertinent clinical and
      laboratory characteristics were collected. RESULTS: Of 323 men with newly
      diagnosed type 2 DM, 31% had ED; comparing potent men and men with ED, there were
      statistically significant differences for smoking, duration of smoking,
      hypertension, education level, body mass index and serum glycosylated haemoglobin
      level. Among these, age was the most important risk factor identified by
      multivariate logistic regression. CONCLUSION: About a third of men with newly
      diagnosed type 2 DM had ED; this was associated with many variables, but most
      notably with age at presentation.

PMID- 17026598
TI  - Testicular microlithiasis: what does it mean clinically?
AB  - OBJECTIVE: To review our current practice of follow-up for boys with testicular
      microlithiasis (TM), an uncommon condition characterized by calcification within
      the seminiferous tubules, detected by ultrasonography (US); TM has been
      associated with both benign and malignant conditions of the testes but the
      natural history of TM in children remains unclear. PATIENTS AND METHODS: All boys
      diagnosed with TM over a 14-year period were included in this study. A search of
      the radiology database was carried out using the keywords 'testicular
      microlithiasis' and 'testicular calcification'. A retrospective case-note review
      was then used to determine age at diagnosis, presenting symptoms, indication for
      testicular US, outcome and follow-up. We also searched Medline/PubMed, using the
      same keywords for published data on TM from 1970 to 2006. RESULTS: Over the study
      period 711 testicular scans were taken in 623 patients; seven cases (1.1%) of TM
      were identified. The mean (range) age at presentation was 12 (7-15) years. The
      presenting symptoms were testicular pain (three), undescended testes (two),
      hydrocele (one) and asymptomatic scrotal swelling (one). In five cases the TM was
      bilateral and in two a solitary kidney was identified. Only one patient had
      tumour markers measured (beta-human chorionic gonadotrophin and alpha
      fetoprotein) and these were within normal limits. On yearly US follow-up, the TM
      was less prominent in one patient, unchanged in four and two were lost to follow
      up. Three patients are currently on yearly US follow-up while two are under the
      care of adult general surgeons. The analysis of reports published to date
      indicated that malignancy only develops when TM is associated with other
      predisposing factors. CONCLUSION: There is no convincing evidence that TM alone
      is premalignant. However, when it accompanies other potentially premalignant
      features we recommend annual US follow-up.

PMID- 17026599
TI  - Clinicians' attitudes to prostate cancer peer-support groups.
AB  - OBJECTIVE: To assess clinicians' knowledge and attitudes to prostate cancer peer
      support groups, essential in improving support services for men with prostate
      cancer, as patients' perceptions of their clinicians' attitudes to such groups
      predict patients' positive and negative perceptions of their experiences at such
      groups. SUBJECTS AND METHODS: In all, 36 clinicians (75% response) across
      Australia, of whom 27 were urologists and nine were radiation oncologists, were
      interviewed in-depth using a key-informant approach. Nine clinicians were from
      regional Australia, with the remaining 27 from major metropolitan settings.
      Subsequently, 30 clinicians (69% response) completed surveys to confirm
      identified themes. RESULTS: Peer support was rated positively by most clinicians
      and most report a fair to good knowledge of such groups. However, less than a
      quarter regularly refer their patients to these groups. While clinicians can
      describe positive aspects of peer support, many are concerned that biased
      viewpoints and misinformation within these groups might potentially contribute to
      patients' decisional uncertainty and regret. CONCLUSIONS: Further research is
      needed to establish for whom these support groups are most helpful. Concerns
      about misleading information that might be proffered in support groups is a
      barrier to clinician referral to these groups. Dialogue between prostate cancer
      interest groups and clinicians to resolve concerns presents as a key strategy to
      improve support for men with prostate cancer.

PMID- 17026600
TI  - A dynamic journal for a dynamic profession.

PMID- 17026601
TI  - The path to modern industrial colour measurement.

PMID- 17026602
TI  - From lower to higher colour metrics: a historical account.
AB  - BACKGROUND: 'Lower colour metrics' describes the laws of colour mixture as
      manifest in trichromatic colour space and best known in its two-dimensional
      projection, the chromaticity diagram. 'Higher colour metrics' describes how
      distance in this colour space translates into perceptual difference. It is higher
      in the sense that it builds on the fundamentals of lower colour metrics. METHODS:
      A historical account is given of the development of higher colour metrics, with
      many ups and downs, since Helmholtz started it at the end of the 19th Century.
      RESULTS: Despite long periods of silence, Helmholtz's basic ideas have survived
      by successfully extended modelling, which could also account for seemingly
      paradoxical effects of luminance and saturation on colour discrimination.
      CONCLUSION: The subject theme, which presently is at a low tide of interest,
      deserves the renewed interest of colour vision researchers.

PMID- 17026603
TI  - Sarcoidosis: case report and review.
AB  - Sarcoidosis is a granulomatous disorder of uncertain aetiology that can affect
      almost any organ. Anterior uveitis is a feature of the condition in about 30 per
      cent of those affected. We describe a patient with sarcoidosis presenting with
      anterior uveitis and describe a diagnostic approach. Sarcoidosis is a condition
      that must be considered in patients presenting with symptomatic uveitis, as the
      underlying disease is serious and usually treatable. The diagnosis of sarcoidosis
      is aided by an understanding of the pattern of organ involvement and may
      ultimately require tissue confirmation through biopsy of granulomata, including
      those found in the ocular adnexa.

PMID- 17026604
TI  - Monocular and binocular thresholds for abruptly and gradually presented illusory
      contours.
AB  - BACKGROUND: In this study, monocular thresholds and binocular summation for
      abrupt onset/offset versus gradually revealed phantom letter E (illusory
      contours) stimuli are compared to determine the suitability of these stimuli for
      assessment of the integrity of two of the major retinal streams: the
      magnocellular and the parvocellular pathways. Such tests are important in
      progressive retinal disease where disease severity may differ between the classes
      of retinal ganglion cells and between the two eyes. Abrupt onset phantom contours
      have long been considered to activate the magnocellular visual pathway and we
      propose that gradually revealed high contrast ramped onset/offset stimuli are
      more likely to promote the more sustained processing of the parvocellular stream.
      METHODS: Contrast discrimination thresholds for monocular and binocular viewing
      were compared in a counter-balanced order in 70 young normal subjects, using
      tests of contrast threshold for a flicker-defined letter E produced by
      alternation of light and dark dots. Three onset/offset conditions were used -
      abrupt onset that was maintained for 34 milliseconds (four frames of 8.5
      milliseconds) then discontinued, ramped onset over 34 milliseconds (four frames)
      with offset over 34 milliseconds and ramped onset over 85 milliseconds (10
      frames) with offset over 85 milliseconds. RESULTS: Contrast thresholds for
      identification of the orientation of the E, when presented with four frames
      ramped onset and offset when compared to the four frames abrupt onset/offset were
      three times higher, irrespective of monocular or binocular viewing conditions.
      Threshold contrasts were seven times higher when the 10 frames ramped
      onset/offset stimuli were compared to abrupt four frames onset/offset. Binocular
      contrast thresholds were reduced by approximately 40 per cent compared to
      monocular thresholds for all conditions. The binocular increase in contrast
      sensitivity is approximately equal for abrupt transiently presented stimuli and
      for gradually presented more sustained stimuli. DISCUSSION: The results indicate
      that the same mechanisms of monocular processing and binocular summation are used
      for identification of a flickering contrast-defined phantom contour under
      presentation conditions, which are characteristic of the temporal and contrast
      preferences of the primate magnocellular and parvocellular visual pathways. This
      suggests that the phantom contour E test may be useful for clinical
      differentiation of the integrity of the M and P retinal ganglion-derived visual
      pathways, regardless of whether it is applied monocularly or binocularly.

PMID- 17026605
TI  - A novel method to measure oxygen permeability and transmissibility of contact
      lenses.
AB  - PURPOSE: The present paper describes an accurate and cost-effective method
      requiring simple equipment to measure the oxygen permeability and
      transmissibility of contact lenses. METHOD: The method involves accurate
      measurement of oxygen across the material by allowing the gas (oxygen) to pass
      through the lens material in a specially fabricated lens mould. The expelled gas
      is collected by dissolution in ethanol and the oxygen is measured by titration of
      the solvent. RESULT: This method is suitable for the measurement of oxygen
      permeability and transmissibility of contact lenses of varying thickness and
      different radii of curvature. It can measure Dk and Dk/t of collagen bandage
      lenses in both wet and dry conditions. CONCLUSION: The oxygen permeability and
      transmissibility values obtained by this method were compared with the oxygen
      permeability standard values of commercially available contact lenses and the
      results are summarised.

PMID- 17026606
TI  - Effect of Proview self-tonometry on pharmaceutical compliance.
AB  - AIM: To evaluate changes in patient compliance with medical treatment while using
      the Proview Eye Pressure Monitor. METHODS: A crossover study design was used to
      compare the compliance of patients with established use of topical medication to
      lower intraocular pressure in the treatment of primary open-angle glaucoma.
      Thirty-two patients currently managed with latanoprost 0.005%, brimonidine 0.15%,
      travoprost 0.004% or bimatoprost 0.03% as monotherapy or in combination were
      randomly assigned to two study groups. Group 1 was instructed in the use of
      Proview Eye Pressure Monitor three times daily for 30 days as an adjunct to the
      glaucoma regimen. Group 2 was observed with no change in the patients' treatment
      regimen during this phase of study. A crossover occurred at 30 days. Compliance
      was monitored by assigning new bottles of topical medication during each phase of
      study. Bottles were weighed with a Mettler balance (Mettler Toledo Co.) at the
      initiation and completion of each phase. The changes in bottle-weight determined
      the amount of medication consumed by each patient for each phase of the study.
      The weights were analysed to estimate changes in compliance. RESULTS: A paired
      samples Student t-test compared the consumed bottle weights with and without
      Proview Eye Pressure Monitor usage. No statistical significance or trend was
      identifiable (p = 0.98). Use of the Proview Eye Pressure Monitor did not
      significantly change compliance with adjunct eye drop medication. CONCLUSION: The
      use of the Proview Eye Pressure Monitor use did not improve but appeared to
      hinder compliance with glaucoma treatment in this study.

PMID- 17026607
TI  - Delayed surface opacification of a hydroview intraocular lens.
AB  - The insertion of an intraocular lens during cataract surgery is routine but
      delayed opacification of hydrophilic foldable intraocular lenses (IOLs) has been
      increasingly noticed as a late post-operative complication. Such opacification
      may present with reduced visual acuity and can be diagnosed with slitlamp
      biomicroscopy. Lens explantation may be required. We report an 89-year-old female
      presenting with opacification of a Hydroview IOL and correlate the clinical
      findings of the lens in situ with the light microscopy of the explanted lens, as
      well as transmission electron microscopy (TEM), scanning electron microscopy
      (SEM) and elemental analysis. Pathological analysis of an explanted IOL may
      assist in a better understanding of the condition and may become relevant in
      medico-legal proceedings.

PMID- 17026608
TI  - Ocular manifestations of molluscum contagiosum.
AB  - PURPOSE: Two cases of molluscum contagiosum (MC) are presented to illustrate the
      range of potential anterior segment complications of this condition. METHODS:
      Clinical records for two patients diagnosed with MC are retrospectively reviewed.
      Diagnosis and management of both cases are presented. RESULTS: The first patient
      demonstrates a classic presentation of ocular MC. The patient was young and had
      several dermal lid lesions at the time of presentation. The second case
      represents a less common presentation. The patient was an adult and had a single
      lid lesion that was not apparent at the initial examination. Both patients had
      follicular conjunctivitis that resolved with excision of the concomitant eyelid
      lesions. CONCLUSION: MC is a treatable cause of chronic conjunctivitis or
      keratoconjunctivitis. Eye-care providers should be mindful that MC could present
      as a follicular keratoconjunctivitis with or without obvious dermal lid lesions.
      The possibility of immuno-compromise must be considered in patients with multiple
      large lesions, cutaneous lesions that do not respond to standard therapy, or
      recurrent lesions.

PMID- 17026609
TI  - ACGIH defends its guidelines for protection against retinal damage by optical
      radiation.

PMID- 17026611
TI  - Ocular therapeutics.

PMID- 17026615
TI  - Chimera and other fertilization errors.
AB  - The finding of a mixture of 46,XX and 46,XY cells in an individual has been
      rarely reported in literature. It usually results in individuals with ambiguous
      genitalia. Approximately 10% of true human hermaphrodites show this type of
      karyotype. However, the underlying mechanisms are poorly understood. It may be
      the result of mosaicism or chimerism. By definition, a chimera is produced by the
      fusion of two different zygotes in a single embryo, while a mosaic contains
      genetically different cells issued from a single zygote. Several mechanisms are
      involved in the production of chimera. Stricto sensu, chimerism occurs from the
      post-zygotic fusion of two distinct embryos leading to a tetragametic chimera. In
      addition, there are other entities, which are also referred to as chimera:
      parthenogenetic chimera and chimera resulting from fertilization of the second
      polar body. Furthermore, a particular type of chimera called 'androgenetic
      chimera' recently described in fetuses with placental mesenchymal dysplasia and
      in rare patients with Beckwith-Wiedemann syndrome is discussed. Strategies to
      study mechanisms leading to the production of chimera and mosaics are also
      proposed.

PMID- 17026616
TI  - Presymptomatic and predictive genetic testing in minors: a systematic review of
      guidelines and position papers.
AB  - The objective of this study is to review ethical and clinical guidelines and
      position papers concerning the presymptomatic and predictive genetic testing of
      minors. The databases Medline, Philosopher's Index, Biological Abstracts, Web of
      Science and Google Scholar were searched using keywords relating to the
      presymptomatic and predictive testing of children. We also searched the websites
      of the national bioethics committees indexed on the websites of World Health
      Organization (WHO) and the German Reference Centre for Ethics in the Life
      Sciences, the websites of the Human Genetics Societies of various nations indexed
      on the website of the International Federation of Human Genetics Societies and
      related links and the national medical associations indexed on the website of the
      World Medical Association. We retrieved 27 different papers dealing with
      guidelines or position papers that fulfilled our search criteria. They
      encompassed the period 1991-2005 and originated from 31 different organizations.
      The main justification for presymptomatic and predictive genetic testing was the
      direct benefit to the minor through either medical intervention or preventive
      measures. If there were no urgent medical reasons, all guidelines recommend
      postponing testing until the child could consent to testing as a competent
      adolescent or as an adult. Ambiguity existed for childhood-onset disorders for
      which preventive or therapeutic measures are not available and for the timing of
      testing for childhood-onset disorders. Although the guidelines covering
      presymptomatic and predictive genetic testing of minors agree strongly that
      medical benefit is the main justification for testing, a lack of consensus
      remains in the case of childhood-onset disorders for which preventive or
      therapeutic measures are not available.

PMID- 17026620
TI  - Inherited association of breast and colorectal cancer: limited role of CHEK2
      compared with high-penetrance genes.
AB  - We assessed the association between breast cancer (BC) and colorectal cancer
      (CRC) from referral pattern to the Regional Genetics Service including molecular
      analysis. Hospital computer records and/or department referral books were used to
      identify cases referred to the Regional Genetic Service during a 16-year period
      (1990-2005 inclusive). All files were reviewed along with associated demographic
      data, risk assessments, referral details and results from mutation testing.
      Families were assessed for hereditary breast and colorectal cancer (HBCC)
      criteria, and all families with eligible individuals were tested for the 1100delC
      mutation in CHEK2. A total of 8,612 families were identified. One hundred and
      sixteen of 1,631 (7.5%) families with a primary referral for CRC fulfilled the
      criteria for HBCC, whereas only 68/6981 (1%) BC referrals fulfilled these
      criteria. Blood samples were obtained from 113 individuals from 83/184 families.
      Only 1/113 (1%) has screened positive for the CHEK2 mutation, whereas 14 (17%)
      families segregate BRCA1/2 mutations and at least 7 (8.5%) carry MLH1/MSH2
      mutations. HBCC syndrome, if it exists as a separate entity, is not likely to be
      due to CHEK2 mutations. Many families are explicable by existing high-penetrance
      genes, and further work is necessary to elucidate whether the remainder is due to
      chance or as yet undiscovered genes.

PMID- 17026621
TI  - Maturity of judgement in decision making for predictive testing for nontreatable
      adult-onset neurogenetic conditions: a case against predictive testing of minors.
AB  - International guidelines developed to minimize harm from predictive testing for
      adult-onset, nontreatable neurogenetic conditions such as Huntington disease (HD)
      state that such testing should not be available to minors. Some authors have
      proposed that predictive testing for these conditions should be available to
      minors at the request of parents and/or of younger adolescents themselves. They
      highlight the lack of empirical evidence that predictive testing of minors causes
      harm and suggest that refusing to test minors may be detrimental. The current
      study focuses on the context of predictive test requests by adolescents younger
      than 18 years, and presents arguments and evidence that the risk of potential
      harm from testing such young people is sufficiently high to justify continued
      caution in this area. A study based on a model of psychosocial maturity found
      that the 3 factors involved in maturity of judgement in decision making -
      responsibility, temperance and perspective - continue to develop into late
      adolescence. There is also evidence that the prefrontal areas of the brain, which
      are involved in executive functions such as decision making, are not fully
      developed until early adulthood. Combined with evidence of adverse long-term
      effects, from research with adults who have undergone predictive testing, these
      findings constitute grounds for retaining a minimum age of 18 years for
      predictive testing for nontreatable conditions. Further research on assessment of
      maturity will assist with reaching a consensus on this issue.

PMID- 17026622
TI  - Association of the CT gene (CA) polymorphism with BMD in osteoporotic Mexican
      women.
AB  - Calcitonin (CT) plays a role in the pathogenesis of osteoporosis and genetic
      variations in or adjacent to the CT gene may be associated with loss of bone
      mineral density (BMD). The correlation between a dinucleotide (cytosine-adenine)
      repeat polymorphism at the CT locus and BMD was examined in 70 osteoporotic
      women, 70 non-osteoporotic women and 500 subjects from the Mexican population.
      The allele A and genotype AA frequencies were significantly higher in
      osteoporotic women than in non-osteoporotic women (60% vs 32%; p < 0.0001 and 41%
      vs 14%; p = 0.0007, respectively). Genotype AA was associated with the presence
      of osteoporosis [odds ratio 2.58; 95% confidence interval (CI); 1.62-4.12].
      Likewise, the loss of lumbar BMD and T scores were related to the presence of
      allele A: subjects with a single A allele displayed lower values for lumbar BMD
      and T score (84.02% and -1.51, respectively) than those who do not present any A
      allele (89.61% and -0.88, respectively). Individuals with two alleles A showed
      the lowest lumbar BMD and T-score values (73.77% and -2.51, respectively).
      Analysis of potential confounder demonstrated that aging has a significant effect
      on osteoporosis development (odds ratio 1.1; 95% CI; 1.1052-1.152).

PMID- 17026623
TI  - An updated mutation spectrum in an Australian series of PJS patients provides
      further evidence for only one gene locus.
AB  - The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be
      associated with mutations in the serine threonine kinase 11 (STK11) gene but only
      a proportion of probands have been shown to harbour changes in the gene. The
      remaining patients were proposed to be either associated with a second PJS gene
      or they harboured more cryptic mutations within the STK11 gene itself. With the
      introduction of the multiplex ligation probe amplification (MLPA) assay, large
      sequence losses or gains can be more readily identified. In this report we have
      screened 33 PJS patients from unrelated families, employing a combination of
      denaturing high-performance liquid chromatography, direct DNA sequencing and the
      MLPA assay to identify deleterious changes in the STK11 gene. The results
      revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic
      mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene
      deletions. No phenotypic differences were identified in patients harbouring large
      deletions in the STK11 gene compared to patients harbouring missense or nonsense
      mutations. Mutation analysis in PJS should include techniques such as MLPA to
      identify large exonic or whole-gene deletions and rearrangements. The high
      proportion of families with identifiable mutations in the STK11 gene using this
      range of techniques suggests that most, if not all PJS, is attributable to
      mutations in the STK11 gene, perhaps including as yet undiscovered changes in
      promoter or enhancer sequences or other cryptic changes.

PMID- 17026624
TI  - Origin of the SCA7 gene mutation in South Africa: implications for molecular
      diagnostics.

PMID- 17026625
TI  - Large deletions of the MECP2 gene in Chinese patients with classical Rett
      syndrome.

PMID- 17026626
TI  - A novel mutation in BAP/SIL1 gene causes Marinesco-Sjogren syndrome in an
      extended pedigree.

PMID- 17026627
TI  - Introduction: genetic diversity and science communication.

PMID- 17026628
TI  - The post-Human Genome Project mindset: race, reliability, and health care.
AB  - The following essay reports on the first session of a 2-day workshop on genetic
      diversity and science communication, organized by the Institute of Genetics. I
      argue that the four talks in this session reflected two different facets of a
      'post-Human Genome Project (HGP)' view of human genetics. The first is
      characterized by an increasing interest in genetic differences. Two speakers -
      Troy Duster and Jasber Singh - expressed skepticism about one aspect of this
      trend: an emphasis on race in medicine and genetics. The other two speakers -
      Kenneth Weiss and Gustavo Turecki - spoke to a second facet of the post-HGP view:
      a recognition of the difficulty in translating genetic discovery into medical or
      public health applications. Though both sets of talks were highly critical of
      current trends in genetic research, they pulled in opposite directions: one
      warned about the role of genetics in stabilizing racial categories, while the
      other lamented the failure of any genetic claims or categories to stabilize at
      all. I argue that the use of racial categories in medicine seems likely to
      encounter scientific, medical, and social challenges.

PMID- 17026629
TI  - The challenges of translating genomic knowledge.
AB  - Knowledge translation has been described as 'the exchange, synthesis and
      ethically-sound application of research findings within a complex set of
      interactions among researchers and knowledge users'. While the objectives of
      knowledge translation have been geared to accelerating the transfer of knowledge
      from producers to users, this essay argues that translation processes are seldom
      linear and are much more complex. Using the examples of how scientific
      institutions and the media communicate with various publics and how publics
      respond to or make use of genomic and genetic information presented at the
      workshop, this report suggests that the complexities of translation - who does
      it, how, using what assumptions, towards what ends, need to be examined and
      better understood.

PMID- 17026630
TI  - Assessing risk assessment: genetic testing and screening for complex disease.
AB  - This paper reports on the presentations from the second session of a 2-day
      workshop on genetic diversity and science communication, organized by the
      Institute of Genetics. The four talks in this session (by Sarah Cunningham
      Burley, Gail Geller, Michael Hayden, and Theresa Marteau) focused on the topic of
      risk assessment in the context of genetic testing, screening and preventive
      medicine for complex disease. Each talk underscored the urgency and importance of
      evaluating when and for whom risk assessment may be useful. A recurrent theme was
      the need to attend closely to the diverse ways that risk is constructed,
      perceived and communicated in a variety of contexts and the significant
      implications of this for laypersons as well as experts. Although there was no
      consensus on when genetic risk assessment ceases (or might begin) to be useful,
      ensuing dialogue between presenters and participants reflected what is perhaps a
      new and critical engagement with how risk assessment itself is assessed. In
      response to this impetus, I use the word RISK as a heuristic to identify, extract
      and amplify four tendencies that appear to advance understandings of risk
      assessment towards a more explicitly reflexive, interpretive, and situated form
      of knowing.

PMID- 17026631
TI  - Science communication in transition: genomics hype, public engagement, education
      and commercialization pressures.
AB  - This essay reports on the final session of a 2-day workshop entitled 'Genetic
      Diversity and Science Communication', hosted by the CIHR Institute of Genetics in
      Toronto, April 2006. The first speaker, Timothy Caulfield, introduced the
      intersecting communities that promulgate a 'cycle of hype' of the timelines and
      expected outcomes of the Human Genome Project (HGP): scientists, the media and
      the public. Other actors also contribute to the overall hype, the social science
      and humanities communities, industry and politicians. There currently appears to
      be an abatement of the overblown rhetoric of the HGP. As pointed out by the
      second speaker, Sharon Kardia, there is broad recognition that most phenotypic
      traits, including disease susceptibility are multi-factorial. That said, George
      Davey-Smith reminded us that some direct genotype-phenotype associations may be
      useful for public health issues. The Mendelian randomization approach hopes to
      revitalize the discipline of epidemiology by strengthening causal influences
      about environmentally modifiable risk factors. A more realistic informational
      environment paves the way for greater public engagement in science policy. Two
      such initiatives were presented by Kardia and Jason Robert, and Peter Finegold
      emphasized that science education and professional development for science
      teachers are important components of later public engagement in science issues.
      However, pressures on public research institutions to commercialize and seek
      industry funding may have negative impacts in both encouraging scientists to
      inappropriately hype research and on diminishing public trust in the scientific
      enterprise. The latter may have a significant effect on public engagement
      processes, such as those proposed by Robert and Kardia.

PMID- 17026632
TI  - Conclusion: genetic diversity and science communication - some issues of
      'translation' and language.
AB  - This commentary concerns some key themes from the symposium. While molecular
      genetics may provide new opportunities to articulate biological concepts of race,
      the ideological baggage associated with the term suggests that it is best dropped
      from discussions. In screening programmes and genetic practice, ethnic identity
      is likely to be an uncertain surrogate to identify individuals with particular
      genetic variants. Precise language and explanation will aid communication about
      genetic matters. Talking of genes for particular traits or diseases is unhelpful.
      School teaching of classic Mendelian genetics is ineffective and should be
      replaced with some teaching of elementary developmental biology based on matters
      of everyday salience and interest. Social science literature is replete with
      unfounded claims of geneticization.

PMID- 17026635
TI  - Is overweight based on BMI a good predictor of risk for hypertension among
      adolescents?

PMID- 17026636
TI  - Law as a tool to improve the health of children and adolescents in schools.

PMID- 17026637
TI  - Enhancing No Child Left Behind-School mental health connections.
AB  - The No Child Left Behind Act of 2001 was signed into law by President George W.
      Bush in January 2002 and is regarded as the most significant federal education
      policy initiative in a generation. The primary focus of the No Child Left Behind
      Act is on promoting educational success for all children; however, the
      legislation also contains opportunities to advance school-based mental health.
      Unfortunately, the complexities of the provisions of the No Child Left Behind Act
      have made it difficult for educators, stakeholders, and mental health
      professionals to understand the legal and practical interface between No Child
      Left Behind and the school mental health movement. Therefore, the goals of this
      article are to (1) raise awareness about the challenges educators and school
      mental health professionals face as a result of the implementation of No Child
      Left Behind and (2) provide ideas and recommendations to advance the interface
      between No Child Left Behind and school mental health, which will support key
      provisions of the act and the growth of the field.

PMID- 17026638
TI  - Implementation of an aggressive random drug-testing policy in a rural school
      district: Student attitudes regarding program fairness and effectiveness.
AB  - School districts are increasingly initiating random drug-testing (RDT) programs
      in an effort to curb substance-use rates among students, yet little is known
      about student attitudes toward RDT and potential obstacles to program acceptance
      and effectiveness. The authors surveyed 1011 9th through 11th grade students in 2
      rural high schools in North Florida regarding the pending implementation of one
      of the most aggressive RDT programs in the nation. A significant majority of
      students predicted that RDT would be effective, yet students were more clearly
      divided in their perceptions of the fairness and the accuracy of testing. Student
      perceptions of whether there is a drug problem at their school proved to be a
      robust predictor of perceptions of policy fairness. Student substance-use rates
      were more limited predictors of policy effectiveness and fairness. These results
      may prove useful to school administrators, health professionals, and policy
      makers seeking to build acceptance for RDT in their schools.

PMID- 17026639
TI  - Assessing the use of school public address systems to deliver nutrition messages
      to children: Shape up Somerville--audio adventures.
AB  - Given the current childhood obesity epidemic, it is especially important to find
      effective ways to promote healthful foods to children. School public address (PA)
      systems represent an inexpensive and a replicable way of reaching children with
      health messages. To test the effectiveness of this channel, messages were created
      to promote 2 dried bean (legume) dishes that had been added to the school lunch
      menu. Six elementary schools were pair matched, and 1 school from each pair was
      randomly chosen to play the messages. The impact of the intervention on choice of
      the 2 new entrees was assessed. Results indicate that for all schools combined,
      choice was not significantly affected. However, compared to their matched control
      schools, choice was significantly higher in the school that received the highest
      dose of the intervention and was significantly lower in the school that received
      the lowest dose. Choice was not changed in the school that received an
      intermediate dose. These results suggest that PA systems show promise as an
      effective and appropriate communications channel but only in schools that are
      able to play messages frequently.

PMID- 17026640
TI  - Bullying and smoking: Examining the relationships in Ontario adolescents.
AB  - Using data from the 2003 Ontario Student Drug Use Survey (Centre for Addiction
      and Mental Health, Toronto), the relationships between bullying and smoking in
      adolescents were examined. A representative sample of 3314 grade 7-12 students
      was included in the analysis. Models were adjusted for confounders identified in
      the current literature. Multinomial logistic regression showed that current
      smokers were more likely to be bullies than nonsmokers (relative risk ratio =
      2.3, p < .001); being a current smoker was not associated with being a victim or
      a bully/victim (one who is both a bully and a victim). Moreover, gender was found
      to modify the effect of smoking on bullying status. Female smokers were more
      likely to be bullies and bully/victims than nonsmokers while there were no
      statistically significant differences for males. The associations between
      bullying status and smoking are consistent with those found in a multinational
      World Health Organization survey of adolescent health. Findings of the study
      suggested that girls were at much higher risk for involvement in bullying if they
      smoked, although girls were less frequently involved in bullying.

PMID- 17026642
TI  - Assuring the safety of severely food allergic children in school.

PMID- 17026641
TI  - Validating an asthma case detection instrument in a Head Start sample.
AB  - Although specific tests screen children in preschool programs for vision,
      hearing, and dental conditions, there are no published validated instruments to
      detect preschool-age children with asthma, one of the most common pediatric
      chronic conditions affecting children in economically disadvantaged communities
      of color. As part of an asthma education intervention, a 15-item Brief
      Respiratory Questionnaire (BRQ) was developed to detect children with probable
      asthma in Head Start and subsidized preschool settings in communities with high
      asthma prevalence and associated morbidity. Preschool personnel administered the
      BRQ to consenting parents of 419 enrolled children. Trained interviewers
      administered validation interviews (VALs) to parents of 149 case-positive
      children and 51 case-negative children. Three physicians independently assessed
      deidentified summaries of the VALs that captured responses about signs and
      symptoms of asthma, diagnosis and treatment, and use of medical services. The
      physicians' assessments of the summarized VALs were the validated standard to
      which the BRQ classifications were compared. A simple algorithm of 4 items was
      identified that can be administered and scored by nonmedical preschool personnel
      in less than 5 minutes. The chance-corrected agreement between these 4 items of
      the BRQ and the VAL was good: kappa, .73 (95% confidence interval, 0.62-0.84);
      specificity, 96%; sensitivity, 73%; and positive predictive value, 97%. The BRQ
      appears to be a valid instrument for detecting children with probable asthma in
      Head Start and other subsidized preschool settings in communities with high
      prevalence of asthma.

PMID- 17026644
TI  - Contrast nephropathy following computed tomography angiography of the chest for
      pulmonary embolism in the emergency department.
AB  - OBJECTIVE: To estimate the frequency of contrast nephropathy after computed
      tomography angiography (CTA) to rule out pulmonary embolism (PE) in the emergency
      department (ED) setting. METHODS: We prospectively followed patients undergoing
      CTA for PE, while in the ED, for 45 days. Patients who refused follow-up or were
      receiving hemodialysis were excluded. Severe renal failure was defined as an
      increase in creatinine > or = 3.0 mg dL(-1) or a need for hemodialysis within the
      follow-up period. Patients were also followed for laboratory-defined contrast
      nephropathy, defined as an increase in creatinine of > 0.5 mg dL(-1) or > 25%,
      within seven days following CTA. RESULTS: A total of 1224 patients were followed,
      and 354 [29%, 95% confidence interval (CI): 26-32%] patients had paired (preCTA
      and post-CTA) creatinine measurements. None developed renal failure (0/1224; 0%,
      CI: 0-0.3%). 44 patients developed laboratory-defined contrast nephropathy,
      corresponding to an overall frequency of 4% (44/1224; CI: 3-5%) and 12% (44/354;
      95% CI: 9-16%) among those with paired creatinine measurements. CONCLUSIONS:
      Following CTA for PE, the incidence of severe renal failure was very low, but the
      incidence of laboratory-defined contrast nephropathy (4% overall and 12% of those
      with paired measurements) was higher than expected.

PMID- 17026645
TI  - Value of D-dimer testing to decide duration of anticoagulation after deep vein
      thrombosis: yes.

PMID- 17026646
TI  - Performance of quantitative D-dimer methods: results of the Italian external
      quality assessment scheme.

PMID- 17026647
TI  - Platelet activation and cardiovascular outcomes in acute coronary syndromes.

PMID- 17026648
TI  - Platelet hyperactivity and risk of recurrent thrombosis.

PMID- 17026649
TI  - Attempts to make sense of the antiphospholipid syndrome.
AB  - Many investigators have been intrigued by the paradoxical association of a
      circulating anticoagulant, first called lupus anticoagulant by Feinstein and
      Rapaport [1], with a tendency to develop thrombosis, as initially described by
      Walter Bowie [2]. Work in Leuven on this topic started when Luis Carreras, an
      Argentinian hematologist, joined the laboratory of blood coagulation at this
      university in 1979. At that time, the head of the laboratory was Marc Verstraete.
      Luis had a particular interest in antibody-mediated coagulation disorders, and
      had prepared reviews on thrombosis and thrombocytopenia induced by heparin [3]
      and on the lupus inhibitor [4]. In Leuven, he joined Jos Vermylen, senior member
      of the laboratory, and an internist with particular interest in hemostasis,
      thrombosis and vascular disease. As such, Professor Vermylen was involved in both
      laboratory research and patient care.

PMID- 17026650
TI  - Experimental studies on the nature of sensitive skin.
AB  - BACKGROUND: In the USA, Europe and Japan 40 to 50% of women report that they have
      sensitive skin, defined as abnormal sub-clinical sensory responses to drugs,
      cosmetics and toiletries in the absence of visible signs of irritation. Itching,
      burning, stinging and tightness are the commonest complaints, which mainly
      afflict women. Manufacturers of skin care products have made available a large
      variety of products which are designed for persons with sensitive skin. Such
      products are not required by regulatory agencies to submit evidence of safety and
      efficacy, allowing marketers to make claims that are often exaggerated,
      irrational and even preposterous. The consumer with self-assessed sensitive skin
      has no way of judging which products are likely to be most beneficial and least
      harmful. The marketplace is awash with products for which there is no evidence
      that the rosy claims have been substantiated by appropriate testing procedures.
      There is no internationally accepted consensus regarding the criteria which
      define sensitive skin. Many papers have been published in the last 15 years,
      mainly originating from industry, which express widely differing views regarding
      what constitutes sensitive skin. For some, any adverse reaction to a product
      topically applied to sensitive skin, including breakouts, redness, scaling etc.,
      a panoply of adverse reactions which is virtually meaningless. Others include
      environmental factors as causative, including cold, dry wind, heat and high
      humidity, solar radiation, etc., which add to the manifest complexities of the
      subject. METHODS: This is the first paper in a series which provides a
      comprehensive review of the subject, emphasizing the all too many controversies
      and confusions arising from the lack of a consensus regarding the identification,
      classification, epidemiology, prevalence and pathogenesis of sensitive skin.
      Sensitive skin is a biologic reality and not a psychological, fashionable fantasy
      on the part of impressionable women. RESULT/CONCLUSION: There is an urgent
      necessity to establish rigorous methodologies for estimating the quality and
      severity of sensitive skin, a heterogeneous condition involving multi-factorial
      factors. Subsequent papers in this series will describe in detail the
      experimental approach our group has used to bring some clarity and credibility to
      this querulous, but important subject.

PMID- 17026651
TI  - Assessment of anti-inflammatory activity of Poria cocos in sodium lauryl sulphate
      induced irritant contact dermatitis.
AB  - OBJECTIVE: In the present study, we evaluated the anti-inflammatory activity of
      Poria cocos (PoCo) on experimentally induced irritant contact dermatitis (ICD) in
      a repeated sodium lauryl sulphate (SLS) irritation model. METHODS: The anti
      irritative effect of PoCo was evaluated with a visual score and quantified by non
      invasive bioengineering methods, namely chromametry and transepidermal water
      loss. Three concentrations of PoCo in base cream DAC (amphiphilic emollient;
      German pharmacopoeia) were tested in a 4-day repetitive irritation test using
      SLS. RESULTS: A statistically significant anti-inflammatory activity was observed
      for PoCo by all three methods when applied in parallel to the induction period of
      ICD. Application of PoCo after induction of ICD once a day for 5 days, starting
      just at the end of 4 days, was without any effect. CONCLUSION: An anti
      inflammatory efficacy of PoCo on the elicitation phase of the ICD induced by
      repeated SLS test could be observed and quantified by three independent, non
      invasive biophysical assessment parameters. This effect can be explained by its
      influence on pro-inflammatory enzymes, namely phospholipase A2.

PMID- 17026652
TI  - Acyclovir concentrations in the skin of humans after a single oral dose assessed
      by in vivo cutaneous microdialysis.
AB  - BACKGROUND/PURPOSE: Acyclovir is a synthetic deoxyguanosine analogue used in the
      treatment of certain viral diseases. This drug is effective primarily against
      Herpes simplex virus, Varicella zoster virus and to a lesser extent against
      Epstein-Barr virus and cytomegalovirus. The aim of the study was to determine the
      acyclovir concentrations in plasma and skin (cutaneous microdialysate) and to
      compare its penetration into real (skin) and theoretical peripheral compartment
      after administration of a single 0.4 g oral dose. METHODS: To evaluate the skin
      concentrations of the examined agent in 10 healthy male volunteers linear
      microdialysis probes with 2 kDa molecular-weight cut-off were inserted
      intradermally and were perfused with Ringer solution up to 6 h after drug
      ingestion. RESULTS: The mean maximum acyclovir concentrations in the plasma, skin
      and theoretical peripheral compartment were 3.16+/-0.86, 0.94+/-0.34 and 1.85+/
      0.69 micromol/L, respectively, and were achieved after 1.6+/-0.4, 2.4+/-0.3 and
      3.7+/-0.7 h. The degree of penetration into the real (skin) and theoretical
      peripheral compartment was 0.36+/-0.15 and 0.74+/-0.12, respectively, and the
      differences were statistically significant. Similarly, also, the maximum
      concentration, time to maximum concentration and area under the concentration
      time curve differed significantly between the plasma and skin as well as between
      the skin and the theoretical peripheral compartment. CONCLUSIONS: In selected
      cases skin concentrations should be determined rather than those in blood plasma
      when studying the distribution of orally administered drugs. Evaluation of
      acyclovir concentrations in the skin cannot be replaced by the calculation of the
      theoretical peripheral compartment.

PMID- 17026653
TI  - Measurement of oedema in irritant-exposed skin by a dielectric technique.
AB  - BACKGROUND: Easily applicable water-specific instruments measuring local oedema
      in skin are not available. The aim of this study is to demonstrate quantitative
      assessment of skin oedema with the dielectric technique by measuring increase of
      skin water content related to sodium lauryl sulphate (SLS)-induced irritant
      contact dermatitis. METHODS: Irritant skin reaction and resulting oedema were
      induced by an irritant patch test on volar forearms in 12 healthy volunteers with
      the application of 1% SLS for 6 h. After occlusion the volunteers were divided
      into two groups: the patch test site of group I (six volunteers) received no
      treatment other than a base cream for the skin reaction, while for group II (six
      volunteers) a strong corticosteroid (clobetasol propionate) was applied on the
      irritant skin. During a follow-up of 72 h, erythema was scored visually, and
      irritant-induced oedema was measured with a novel water-specific instrument
      MoistureMeter-D. RESULTS: In the untreated irritant skin, a maximum increase of
      45% in skin water content was found at 10 h postocclusion and water content was
      still elevated at 72 h. With these persons, the degree of oedema agreed well with
      the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated
      skin, an increase of 8% in water content was measured during 72 h but there was
      no correlation between oedema and skin thickness. There was no correlation
      between erythema and oedema in untreated or corticosteroid-treated skin.
      CONCLUSION: The new instrument can easily be applied for noninvasive quantitative
      evaluation of local oedema and fluid retention in irritant-exposed skin.

PMID- 17026654
TI  - Moisturizing effect of cosmetic formulations containing Aloe vera extract in
      different concentrations assessed by skin bioengineering techniques.
AB  - BACKGROUND/PURPOSE: The polysaccharide-rich composition of Aloe vera extracts
      (Aloe barbadensis Miller), often used in cosmetic formulations, may impart
      moisturizing properties to the product. The aim of this study was to evaluate the
      effect of cosmetic formulations containing different concentrations of freeze
      dried Aloe vera extract on skin hydration, after a single and a 1- and 2-week
      period of application, by using skin bioengineering techniques. METHODS: Stable
      formulations containing 5% (w/w) of a trilaureth-4 phosphate-based blend were
      supplemented with 0.10%, 0.25% or 0.50% (w/w) of freeze-dried Aloe vera extract
      and applied to the volar forearm of 20 female subjects. Skin conditions in terms
      of the water content of the stratum corneum and of transepidermal water loss
      (TEWL) (Corneometer CM 825 and Tewameter TM 210) were analysed before and after a
      single and 1- and 2-week period of daily application. RESULTS: After a single
      application, only formulations supplemented with 0.25% and 0.50% (w/w) of Aloe
      vera extract increased the water content of the stratum corneum, while after the
      2-week period application, all formulations containing the extract (0.10%, 0.25%
      and 0.50%) had the same effect, in both cases as compared with the vehicle. TEWL
      was not modified after a single and after 1- and 2-week period of application,
      when compared with the vehicle. CONCLUSION: Our results show that freeze-dried
      Aloe vera extract is a natural effective ingredient for improving skin hydration,
      possibly through a humectant mechanism. Consequently, it may be used in
      moisturizing cosmetic formulations and also as a complement in the treatment of
      dry skin.

PMID- 17026655
TI  - Kinetics of blood flow during healing of excisional full-thickness skin wounds in
      pigs as monitored by laser speckle perfusion imaging.
AB  - BACKGROUND/PURPOSE: The laser speckle perfusion imaging (LSPI) system is a new,
      non-invasive technique for rapidly and reproducibly measuring tissue perfusion.
      The high resolution and frame rate of the LSPI overcome many of the limitations
      of traditional laser Doppler imaging techniques. Therefore, LSPI is a useful
      means for evaluating blood flow in a variety of situations. The present study
      investigates the ability of the LSPI system to detect temporal changes in blood
      flow during the healing of cutaneous wounds in a well-characterized animal model.
      METHODS: Full-thickness excisional skin wounds (2 x 2 cm) were created on the
      backs of juvenile female red Duroc pigs. Every week post-injury, the wounds were
      measured and photographed, and normalized blood flow values were determined using
      the LSPI system. RESULTS: Tissue perfusion values were available after complete
      re-epithelialization and removal of the eschar, at day 21. At this point, wound
      blood flow was significantly elevated as compared with the surrounding,
      uninvolved skin. Wound blood flow declined steadily during healing, and
      approached normal values by day 35 post-injury. CONCLUSION: The kinetics of blood
      flow during excisional wound healing in the red Duroc model are comparable with
      that previously observed in laser Doppler imaging of healing human skin wounds
      and hypertrophic scars. These results therefore confirm that the red Duroc is a
      good model of human wound healing, and further indicates that the LSPI is an
      excellent technique for evaluating angiogenesis and neovascularization during
      healing in this and other models.

PMID- 17026656
TI  - Characterization and quantification of the skin radiance through new digital
      image analysis.
AB  - BACKGROUND/AIMS: The individual perception of the radiance is difficult to define
      and quantify because it often includes physiological and psychological
      attributes. Although if they are differences in the perception of the skin
      radiance, dermatologists and experts in cosmetology consider that the complexion
      must reflect the general health of an individual. The aim of this work was to
      determine existing conditions of skin radiance via digital image analysis,
      consumer's perception and experts' evaluation, and propose a mathematical model
      to quantify the global radiance phenomenon. METHODS: A round table meeting was
      organized in order to have free discussions about skin radiance. The qualitative
      assessment of skin radiance was carried out using a self-assessment questionnaire
      constructed according to the information obtained from the round table meeting. A
      simplified version of this questionnaire was proposed to experts. One hundred
      female subjects belonging to three different age groups (20-30, 30-40, 40-50 and
      >50 years old) participated in the study. Facial images were taken using a video
      imaging with visual control system to ensure consistency of images among
      volunteers. From these images, algorithms based on the principle of polynomial
      approximation, segmentation by maximalization of the entropy and the Logarithmic
      Image Processing model were required to extract skin radiance parameters.
      Multiple regression analysis was used to establish, via consumer's perception of
      the skin radiance and experts' evaluation studies, the degree to which each of
      the independent parameters contributes to the skin radiance perception. RESULTS:
      All the items of the self-assessment questionnaire explained 74% of the variation
      of the skin radiance. Data from experts' analysis explained 87% of the variation
      of skin radiance. In the two cases, skin radiance appeared to be independent of
      age and the presence of wrinkles. From the image analysis, we observed that the
      skin surface parameters explained 20% of the variation of the skin radiance
      expressed by experts and 24% of the variation of the skin radiance expressed by
      volunteers. As a result, about 80% of the variation is not explained by the
      instrumental data. If we combine experts' analysis and instrumental data, we
      obtain a mathematical model that explains 92% of the variation of the skin
      radiance. CONCLUSION: The questionnaire constructed from this brainstorming
      session allowed volunteers and experts to judge their perception of skin radiance
      more precisely. Video imaging appears as an interesting method to quantify visual
      properties of the skin and to visualize what the consumer perceives of skin
      radiance. However, the mathematical model proposed from the skin surface
      parameters analysis does not totally explain the global perception of skin
      radiance. In the future, it will be necessary to develop new data-processing
      programs to quantify subjective parameters in order to validate our mathematical
      model.

PMID- 17026657
TI  - High-resolution optical coherence tomography as a non-destructive monitoring tool
      for the engineering of skin equivalents.
AB  - BACKGROUND: Three dimensional skin equivalents are widely used in
      dermatopharmacological and toxicological studies and as autologous transplants in
      wound healing. In pharmacology, there is tremendous need for monitoring the
      response of engineered skin equivalents to external treatment. Transplantation of
      skin equivalents for wound healing requires careful verification of their quality
      prior to transplantation. Optical coherence tomography (OCT) is a non-contact,
      non-destructive imaging technique for living tissues offering the potential to
      fulfill these needs. This work presents an analysis of OCT for high-resolution
      monitoring of skin equivalents at different stages during the culture process.
      METHODS: We developed a high-resolution OCT imaging setup based on a commercially
      available OCT system. A broadband femtosecond laser light source replaces the
      original superluminescence diode. Tomograms of living skin equivalents were
      recorded with an axial resolution of 3 mum and correlated with histology and
      immunofluorescence images. Comparison with standard low-resolution OCT is
      presented to emphasize the advantages of high-resolution OCT for this
      application. RESULTS: OCT is particularly able to distinguish between different
      layers of skin equivalents including stratum corneum, epidermal and dermal layer
      as well as the basement membrane zone. The high-resolution OCT scans correlate
      closely with two key benchmarks, histology and immunofluorescence imaging.
      CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT
      for identifying living tissue structure and morphology. Compared with the current
      gold standard histology, OCT offers non-destructive tissue imaging, enabling high
      resolution evaluation of living tissue morphology and structure as it evolves.

PMID- 17026658
TI  - Reference ranges of skin micro-relief according to age in French Caucasian and
      Japanese women.
AB  - BACKGROUND/PURPOSE: The variation of skin surface morphological indicators
      according to age has not been frequently studied. The aim of this work was to
      establish French Caucasian and Japanese reference ranges of these indicators
      according to age. METHODS: Two studies were performed simultaneously in Paris and
      Sendai on 356 Caucasian and 120 Japanese healthy women aged from 20 to 80 years.
      Skin replicas were obtained from the volar forearm and analysed by
      interferometry. This analysis yielded 16 morphological indicators. Reference
      ranges according to age were established using the statistical methodology
      defined by Royston. RESULTS/DISCUSSION: Reference ranges were found for 15 out of
      the 16 parameters for the French women as well as for the Japanese women. The
      models' truthfulness will have to be confirmed using new samples, larger if
      possible. Moreover, non-parametric methods will be used in order to compare the
      results provided by these approaches.

PMID- 17026659
TI  - Mechanobiology and force transduction in scars developed in darker skin types.
AB  - BACKGROUND: Scarring is a complex process involving many cell types, cytokines
      and biological pathways including mechanobiology. Some subtle mechanical
      properties of skin can be assessed by measuring the speed of ultrasound shear
      wave propagation. The orientation of abnormal skin tension forces can be
      visualized, particularly in darker skin types, using dermoscopy showing distinct
      patterns of rete ridges' conformation. AIM: To assess some mechanobiological
      features of scars in darker skin types. PATIENTS AND METHODS: Large atrophic and
      hypertrophic surgical scars were examined on the trunk of 35 darker skin
      subjects. The surrounding skin was used as a comparator. Dermoscopic aspects were
      recorded. Resonance running time measurements (RRTM) were performed using a shear
      wave propagation device (Reviscometer). They were performed in four specific
      directions at given angles with regard to the long axis of the scar. The minimum,
      maximum and mean RRTM values were recorded at each site. RESULTS: Dermoscopy
      revealed patterns of melanin deposits in scars distinct from the normal honeycomb
      network seen in the surrounding skin. Hypertrophic scars showed a patchy pattern
      of large macular melanoderma dispersed in a lighter background. In these cases,
      low RRTM values were obtained with little variations according to the orientation
      of the measurements. By contrast, atrophic scars showed a streaky laddering
      melanotic pattern under dermoscopy. Higher RRTM values were often obtained,
      particularly in the transversal direction of the scars. Mechanical anisotropy was
      greater in the atrophic scars compared with the normal skin. DISCUSSION: Darker
      skin types represent a model for visualizing the main orientation of the
      epidermal rete ridges. A correlation was found between the pattern of melanized
      rete ridges of scars and the main orientation of the intrinsic forces in the
      skin.

PMID- 17026660
TI  - Relationships between changes in mechanical properties of the skin, wrinkling,
      and destruction of dermal collagen fiber bundles caused by photoaging.
AB  - BACKGROUND/PURPOSE: Long-term exposure to ultraviolet (UV) radiation induces
      various cutaneous changes that differ from those because of physiological aging,
      including structural destruction of dermal collagen fiber bundles (DCFBs), which
      comprise the major component of the dermis. Wrinkling, a representative change in
      skin surface associated with photoaging, is often seen at the corners of the eyes
      and in the space between the eyebrows. These are locations where the skin
      contracts repeatedly and routinely. Lowered resiliency to skin contraction
      induced by marked structural changes in DCFBs may represent one cause of photo
      induced wrinkles. Using animal models of photoaging, changes in mechanical
      properties of the skin caused by UV irradiation were measured, and relationships
      between UV-induced changes were analyzed. METHODS: Animal models of photoaging
      were prepared by irradiating hairless mice with UVB light. Dorsal skin surface
      replicas of animals were taken using silicon rubber, and volume of wrinkles was
      calculated using an image analyzer. Stress of the skin against horizontal
      contraction was measured using a new device called the Resiliometer. Three
      dimensional organization of dermal collagen structures in skin samples collected
      from the back of each animal was observed under scanning electron microscopy, and
      compactness of DCFBs was assessed from electron micrography. RESULTS: With time
      and therefore increasing UV dose, deep wrinkles formed on the backs of mice.
      Volume of wrinkles peaked at 8 weeks. All parameters obtained from Resiliometer
      measurements were increased by irradiation. DCFB structure was degraded in a
      radiation dose-dependent manner. DCFB grading was significantly correlated with
      each Resiliometer parameter. Significant correlations were also observed between
      each Resiliometer parameter and volume of wrinkles. CONCLUSION: Stress of the
      skin against horizontal contraction obtained using the Resiliometer changes
      following UV irradiation, correlating with photo-induced wrinkling and
      destruction of DCFBs. These results support the hypothesis that changed force of
      restitution to skin contraction induced by marked structural changes in DCFBs
      represents one cause of photo-induced wrinkles. The resiliometric parameter may
      offer a good indicator for monitoring the condition of DCFB structure, as changes
      in these would induce failure in restitution to skin contraction, leading to
      wrinkling.

PMID- 17026661
TI  - Fluorescence digital photography of acne using a light-emitting diode
      illuminator.
AB  - BACKGROUND/PURPOSE: The fluorescence findings of several dermatological diseases,
      such as erythrasma, tinea versicolor, and acne are helpful for diagnosis and
      follow-up. However, many experience difficulty taking photographic images of
      fluorescence. The aim of this study was to develop a 405 nm light-emitting diode
      (LED) system for fluorescence digital photography of acne and to determine
      whether such a diode can be used to evaluate acne. METHODS: Eight healthy acne
      patients were compared with controls by fluorescence digital photography using a
      digital camera equipped with a 405 nm LED illuminator. Digital photographs were
      taken by two different ways of exposure, i.e. appropriate exposure level and
      longer exposure. One side of the nose, cheek, and glabella was compared. The
      numbers and extents of fluorescence dots were counted and measured. As normal
      controls, seven individuals with apparent oiliness and no acne were enrolled.
      RESULTS: Red fluorescent facial dots were observed and photographed digitally
      using the 405 nm LED illuminator. These were more numerous and extensive on the
      glabella and cheeks of acne patients. CONCLUSION: Fluorescence digital
      photography of acne was successfully performed using a 405 nm LED illuminator.
      This illuminator could be used for acne evaluations.

PMID- 17026663
TI  - Application of a pigment measuring device--Mexameter--for the differential
      diagnosis of vitiligo and nevus depigmentosus.
AB  - BACKGROUND/PURPOSE: Vitiligo and nevus depigmentosus (ND) present similar
      hypopigmented macules with significantly different prognoses. Although the
      distinction between the two diseases is important, differential diagnosis relies
      on medical history and physical examination, which is far from decisive in some
      cases. The Mexameter is an objective skin color-measuring device, and has been
      reported to provide a reproducible and sensitive means of quantifying small skin
      color differences. In this study, we investigated the usefulness of a Mexameter
      for discriminating these diseases. METHODS: A selection of 202 hypopigmented skin
      lesions (182 from vitiligo and 20 from ND) were the objects of this study. Using
      a Mexameter, MIs were obtained from lesions and symmetrically located control
      skin. RMIs, ratios of the MIs of lesional skins to control skins, were
      calculated. RESULTS: The mean MIs and RMIs were significantly different for
      vitiligo and ND. The mean RMI of ND lesions was 74+/-13, which was significantly
      higher than that of vitiligo lesions (50+/-24). No ND lesion had an RMI of <50%.
      CONCLUSION: This study shows that the Mexameter, an objective pigment-measuring
      device, can be used to achieve a more accurate diagnosis of hypopigmentary
      disorders, and that the relative melanin index (RMI), which represents the
      relative pigment levels, might be a more effective parameter than the melanin
      index (MI) itself for comparing pigmentation differences.

PMID- 17026662
TI  - Hand-held pulsed photothermal radiometry system to estimate epidermal temperature
      rise during laser therapy.
AB  - BACKGROUND/PURPOSE: During laser therapy of port wine stain (PWS) birthmarks in
      human skin, measurement of the epidermal temperature rise (DeltaT(epi)) is
      important to determine the maximal permissible light dose. In order to measure
      DeltaT(epi) on a specific PWS skin site, we developed an AC-coupled hand-held
      pulsed photothermal radiometry (PPTR) system, which overcomes the in vivo
      measurement limitations of bench-top systems. METHODS: The developed hand-held
      PPTR system consists of an infrared (IR) lens, AC-coupled thermoelectrically
      cooled IR detector, laser hand-piece holder, and positioning aperture. The raw AC
      coupled signal was integrated to obtain a higher signal-to-noise ratio (SNR). The
      experimental temperature difference (DeltaT) calibration was compared with
      theoretical computations. In vitro and in vivo measurements of DeltaT were
      performed with a tissue phantom as a function of radiant exposure and human
      subject as a function of melanin concentration, respectively. RESULTS: The
      integrated AC-coupled signal provided higher SNR as compared with the raw AC
      coupled signal. The experimental DeltaT calibration resulted in good agreements
      with the theoretical results. The in vitro and in vivo results also presented
      good agreements with theory. CONCLUSIONS: A fiber-free, hand-held AC-coupled PPTR
      system is capable of accurate epidermis temperature rise (DeltaT(epi))
      measurements of human skin during pulsed laser exposure.

PMID- 17026664
TI  - A non-invasive method for the in vivo determination of skin antioxidant capacity
      (IAC-S).
AB  - BACKGROUND/PURPOSES: Skin antioxidant network protects cells against oxidative
      injury and prevents the production of oxidation products. When oxidative stress
      overwhelms the skin antioxidant capacity, the subsequent modification of the
      cellular redox apparatus leads to an alteration of cell homeostasis leading to
      degenerative processes. In the dermocosmetic field, the topical application of
      antioxidants is often suggested as a possible strategy to prevent and modulate
      oxidative skin damages. Continuing our studies addressed to set-up new bio
      engineering protocols for the claim substantiation of antioxidant cosmetic
      products, we have developed a new non-invasive methodology for the evaluation of
      antioxidants cosmetics ingredients and finished products. METHODS: The effects of
      a pre-treatment on forearm skin with an antioxidant ingredient were investigated
      on 15 volunteers, in a double-blind randomised fashion. A non-invasive method was
      devised that comprises the collection of forehead SC layers of the pre-treated
      area and control and the next evaluation of skin antioxidant capacity (IAC-S) by
      a luminescence-based method. RESULTS: The results showed that the antioxidant
      preparation was able to increase, to a statistically significant extent (P<0.01),
      the IAC-S in comparison with the control area. The data were confirmed (P<0.05)
      by comparison with a method, previously developed by us, based on DermAnalyzer.
      CONCLUSIONS: In view of the simplicity and reliability of the method here
      presented, this new technique is proposed as a possible tool for the routine
      evaluation of in vivo efficacy of antioxidant functional ingredients and finished
      products.

PMID- 17026665
TI  - Phototrichogram findings in women with androgenetic alopecia.
AB  - BACKGROUND/PURPOSE: Androgenetic alopecia (AGA) in women is characterized by
      diffuse thinning in the frontal and parietal areas of the scalp; preservation of
      the frontal hairline is norm. Hair over the occipital scalp is preserved. The
      purpose of this work was to investigate the findings of phototrichogram (PTG) of
      the affected and the spared areas in women with AGA and to compare them with
      those of healthy subjects. METHODS: Twenty-two controls and 60 untreated women
      with AGA (32 with Ludwig I, 28 with Ludwig II) were included in this study. Hair
      density, percentages of thin hair, and non-growing hair were estimated both on
      the midscalp and on the occiput by using PTG with digital camera attached to a
      dermoscope. RESULTS: In the control group, hair density was higher on the
      midscalp than the occiput. In AGA groups, hair density was lower on the midscalp
      than the occiput and percentages of thin hair and non-growing hair were higher on
      the midscalp than the occiput. These findings were more prominent in Ludwig II
      group. In the occiput there were findings mimicking the changes seen on the
      midscalp. These were less striking than those seen on the midscalp yet the
      difference between the control and Ludwig II group was statistically significant.
      CONCLUSION: We concluded that the hair is not equally distributed on the scalp,
      the occiput may be affected in females with AGA and further studies are necessary
      to support these findings.

PMID- 17026667
TI  - Epitheliocystis in fish.
AB  - Epitheliocystis is a condition affecting the gills and skin of fish, which has
      been reported from more than 50 freshwater and marine species. It is caused by
      intracellular Gram-negative bacteria. Mortalities have been associated with
      epitheliocystis infections in cultured fish. This review provides an update of
      our current understanding of this condition, including characterization of the
      pathogen using immunohistochemical and molecular studies. In most fish species
      the epitheliocystis agent was negative to an antibody specific for chlamydial
      genus-specific lipopolysaccharide antigen. Recently, four epitheliocystis agents
      from four different fish species have been characterized using molecular
      analysis. While they all belong to the order Chlamydiales, in a lineage separate
      from the Chlamydiaceae, they are distinct organisms and similarity analysis
      showed that they had highest similarity values with other chlamydia-like bacteria
      isolated from various sources, including humans or pig. This confirms the high
      diversity and host specificity of the pathogen. Further molecular analysis should
      result in an increased understanding of this condition. To date the pathogen has
      not been cultured, making experimental studies difficult. High stocking
      densities, presence of nutrients, season, temperature and fish age have been
      identified as potential risk factors for the manifestation of this condition.

PMID- 17026666
TI  - Keep the traffic moving: mechanism of the Hsp70 motor.
AB  - Hsp70s are ubiquitous chaperones that use ATP hydrolysis to drive a variety of
      protein processing reactions, including a number of steps in protein trafficking.
      Recent studies have shed light on how ATP might generate conformational changes
      in an Hsp70 molecule and how such changes might be harnessed to drive processes
      as diverse as protein import into subcellular organelles and uncoating of
      clathrin-coated vesicles.

PMID- 17026668
TI  - Pre-exposure to infectious hypodermal and haematopoietic necrosis virus or to
      inactivated white spot syndrome virus (WSSV) confers protection against WSSV in
      Penaeus vannamei (Boone) post-larvae.
AB  - Larvae and post-larvae of Penaeus vannamei (Boone) were submitted to primary
      challenge with infectious hypodermal and haematopoietic necrosis virus (IHHNV) or
      formalin-inactivated white spot syndrome virus (WSSV). Survival rate and viral
      load were evaluated after secondary per os challenge with WSSV at post-larval
      stage 45 (PL45). Only shrimp treated with inactivated WSSV at PL35 or with IHHNV
      infection at nauplius 5, zoea 1 and PL22 were alive (4.7% and 4%, respectively)
      at 10 days post-infection (p.i.). Moreover, at 9 days p.i. there was 100%
      mortality in all remaining treatments, while there was 94% mortality in shrimp
      treated with inactivated WSSV at PL35 and 95% mortality in shrimp previously
      treated with IHHNV at N5, Z1 and PL22. Based on viral genome copy quantification
      by real-time PCR, surviving shrimp previously challenged with IHHNV at PL22
      contained the lowest load of WSSV (0-1x10(3) copies microg-1 of DNA). In
      addition, surviving shrimp previously exposed to inactivated WSSV at PL35 also
      contained few WSSV (0-2x10(3) copies microg-1 of DNA). Consequently, pre-exposure
      to either IHHNV or inactivated WSSV resulted in slower WSSV replication and
      delayed mortality. This evidence suggests a protective role of IHHNV as an
      interfering virus, while protection obtained by inactivated WSSV might result
      from non-specific antiviral immune response.

PMID- 17026669
TI  - Pathogenicity of Edwardsiella tarda to olive flounder, Paralichthys olivaceus
      (Temminck & Schlegel).
AB  - The LD50 and cytotoxic and enzymatic activities of both cells and extracellular
      products (ECPs) of eight Edwardsiella tarda strains were determined and their
      bacterial superoxide dismutase gene (sodB) and catalase gene (katB) were
      sequenced. Strains were also examined for their ability to resist the immune
      responses of olive flounder, Paralichthys olivaceus. LD50 values of strains
      (FSW910410, KE1, 2, 3, 4, 5 and 6) in olive flounder ranged between 10(2.5) and
      10(5.3) cfu (colony forming units) per fish. Unlike the avirulent strain SU100
      (LD50>or=10(7)), all pathogenic strains were able to survive in flounder serum
      and head kidney leucocytes (except for KE2). The virulent strains possessed type
      I sodB and katB, whereas SU100 had type II sodB but not katB. However, there was
      no difference between avirulent and virulent strains in haemolytic and cytotoxic
      activities. The results of this study demonstrated that the ability of E. tarda
      to resist complement activity and phagocytosis is conferred by its superoxide
      dismutase and catalase, which thus play an essential role in the pathogenicity of
      this bacterium. In addition genotyping of sodB and kat B proved to be a very
      useful tool to distinguish virulent from avirulent strains.

PMID- 17026670
TI  - Isolation of viral haemorrhagic septicaemia virus from muskellunge, Esox
      masquinongy (Mitchill), in Lake St Clair, Michigan, USA reveals a new sublineage
      of the North American genotype.
AB  - Viral haemorrhagic septicaemia virus (VHSV) was isolated from muskellunge, Esox
      masquinongy (Mitchill), caught from the NW portion of Lake St Clair, Michigan,
      USA in 2003. Affected fish exhibited congestion of internal organs; the inner
      wall of the swim bladder was thickened and contained numerous budding, fluid
      filled vesicles. A virus was isolated using fish cell lines inoculated with a
      homogenate of kidney and spleen tissues from affected fish. Focal areas of cell
      rounding and granulation appeared as early as 24 h post-inoculation and expanded
      rapidly to destroy the entire cell sheet by 96 h. Electron microscopy revealed
      virions that were 170-180 nm in length by 60-70 nm in width having a bullet
      shaped morphology typical of rhabdoviruses. The virus was confirmed as VHSV by
      reverse transcriptase-polymerase chain reaction. Sequence analysis of the entire
      nucleoprotein and glycoprotein genes revealed the virus was a member of the North
      American genotype of VHSV; however, the isolate was sufficiently distinct to be
      considered a separate sublineage, suggesting its origin may have been from marine
      species inhabiting the eastern coastal areas of the USA or Canada.

PMID- 17026671
TI  - Efficacy of emamectin benzoate against sea lice infestations of Atlantic salmon,
      Salmo salar L.: evaluation in the absence of an untreated contemporary control.
AB  - The efficacy of emamectin benzoate (SLICE) against sea lice infestations of
      Atlantic salmon, Salmo salar L., is typically assessed using untreated fish, or
      fish treated with alternative therapeutants, as controls. The State of Maine,
      USA, is currently under active management for the OIE-notifiable pathogen,
      infectious salmon anaemia virus (ISAV); consequently, neither control group is
      feasible in this region. Untreated salmon risk extensive damage from the
      ectoparasites, and threaten to increase vector-borne exposure or susceptibility
      of farms to ISAV; and the only treatment presently available in Maine is SLICE.
      However, because sea lice infestations are unlikely to resolve spontaneously, and
      response to treatment occurs within weeks, use of a pretreatment baseline is a
      reasonable alternative for confirmatory studies. We evaluated SLICE efficacy on
      Atlantic salmon farms in Cobscook Bay 2002-2005, in the absence of untreated
      controls, using pretreatment lice loads as a reference for calculation. Maximum
      efficacy ranged from 68% to 100% reduction from initial levels. Time-to-maximum
      efficacy ranged from 1 to 8 weeks after treatment initiation. Efficacy duration,
      measured between first reduction and first progressive rise in counts, ranged
      from 4 to 16 weeks.

PMID- 17026672
TI  - Isolation of Flavobacterium psychrophilum from sea lamprey, Petromyzon marinus
      L., with skin lesions in Lake Ontario.

PMID- 17026673
TI  - Susceptibility of the fish cell line SAF-1 to betanodavirus.

PMID- 17026690
TI  - Allergic contact dermatitis to copolymers in cosmetics--case report and review of
      the literature.
AB  - Copolymers or heteropolymers are large molecules with high molecular weights
      (>1000 D). They have been underestimated for a long time as to their sensitizing
      capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a
      medical dressing has been described; however, the nature of the hapten is still
      unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone
      (PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature
      on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene,
      PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy
      PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and
      polyvinyl methyl/maleic acid anhydride.

PMID- 17026691
TI  - Identification and classification of skin sensitizers: identifying false
      positives and false negatives.
AB  - The first step in regulatory evaluation of substances involves the identification
      of their intrinsic hazards, including the potential for skin sensitization. This
      is, quite properly, entirely different from assessment of the risks to human
      health, which might arise from incorporation of substances in products. EU
      guidance on regulations concerning the classification of skin sensitizers
      suggests a range of sources of information be deployed in the hazard
      identification process. These include chemical structure, predictive animal
      tests, and various types of human data. Where the information is clear-cut, then
      uncertainties rarely arise. However, for some materials, discordant information
      arises, perhaps because the substance is on the borderline of test sensitivity
      and classification (sensitizing materials of insufficient potency do not
      classified according to the EU scheme), due to conflicting results in predictive
      tests or for other reasons. In this study, we review data on a number of
      substances where a classification decision is complicated by such discordances
      and seek to use these examples to demonstrate how best to make a weight of
      evidence decision on whether a substance should, or should not, be classified as
      a skin sensitizer.

PMID- 17026692
TI  - Not only oxidized R-(+)- but also S-(-)-limonene is a common cause of contact
      allergy in dermatitis patients in Europe.
AB  - Limonene, one of the most often used fragrance terpenes in any kind of scented
      products, is prone to air-oxidation. The oxidation products formed have a
      considerable sensitizing potential. In previous patch test studies on
      consecutively tested dermatitis patients, oxidized R-limonene has been proven to
      be a good and frequent indicator of fragrance-related contact allergy. The
      current study extends these investigations to 6 European clinics of dermatology,
      where the oxidation mixture of both enantiomers of limonene (R and S) have been
      tested in 2411 dermatitis patients. Altogether, 63 out of 2411 patients tested
      (2.6%) reacted to 1 or both the oxidized limonene preparations. Only 2.3% reacted
      to the oxidized R-limonene and 2.0% to the oxidized S-limonene. In 57% of the
      cases, simultaneous reactions were observed to both oxidation mixtures.
      Concomitant reactions to the fragrance mix, colophonium, Myroxylon pereirae, and
      fragrance-related contact allergy were common in patients reacting to 1 or both
      the oxidized limonene enantiomers. Our study provides clinical evidence for the
      importance of oxidation products of limonene in contact allergy. It seems
      advisable to screen consecutive dermatitis patients with oxidized limonene 3%
      petrolatum, although this patch test material is not yet commercially available.

PMID- 17026693
TI  - The aetiology of eyelid dermatitis: a 10-year retrospective analysis.
AB  - Few studies have examined the aetiology of eyelid dermatitis across broad
      demographics. The objectives of this study were (i) to compare the diagnoses of
      patients with isolated eyelid dermatitis to the diagnoses of patients with
      additional sites of involvement and (ii) to determine the relevant allergens
      among patients with allergic eyelid dermatitis. A retrospective analysis of 1215
      patients patch tested over 10 years was conducted in this study. Compared to
      patients without eyelid dermatitis, patients with this entity were more often
      female. Of the 105 patients with eyelid dermatitis, 43.8% had allergic contact
      dermatitis (ACD), 36.2% seborrhoeic dermatitis, 11.4% other
      dermatitis/dermatoses, 7.6% irritant contact dermatitis, 3.8% psoriasis, and 2.9%
      atopic eczema. With isolated eyelid dermatitis, seborrhoeic dermatitis was the
      most frequent diagnosis (46.3%) followed by ACD (35.2%). Allergens commonly
      causing allergic eyelid dermatitis consisted of fragrances, metals, neomycin,
      oleamidopropyl dimethylamine, tosylamide formaldehyde resin, benzalkonium
      chloride, and other preservatives. When evaluated according to sites of
      involvement, seborrhoeic dermatitis was diagnosed most often in patients with
      isolated eyelid dermatitis, but when dermatitis was distributed to facial or
      other sites, ACD was the most frequent diagnosis. A majority of the causative
      allergens for eyelid dermatitis are not present on the Food and Drug
      Administration-approved panels available in the USA.

PMID- 17026694
TI  - Nickel allergy and hand eczema--a 20-year follow up.
AB  - The aim of this study was to investigate the occurrence of hand eczema after 20
      years in women patch tested to nickel during childhood. In 1982-1983, 960
      schoolgirls were patch tested for nickel allergy; its prevalence was found to be
      9%. 20 years later, the same individuals received a questionnaire regarding hand
      eczema and factors of importance for the development of hand eczema. 735 of 908
      women (80.9%) answered the questionnaire. In total, 17.6% of respondents reported
      hand eczema after the age of 15 years, and the 1-year prevalence was 12.8%. There
      was no statistically significant difference in the occurrence of hand eczema
      between the groups who had previously tested positive and negative for nickel
      allergy. 38.3% of the respondents considered themselves to be nickel sensitive at
      the time they answered the questionnaire; in this group, the reported prevalence
      of hand eczema after age 15 was 22.5%. 31.4% of those with a history of atopic
      dermatitis reported hand eczema after age 15, compared with 10.6% of those
      without (P < 0.001). In conclusion, contact allergy to nickel in childhood did
      not seem to increase the prevalence of hand eczema later in life.

PMID- 17026695
TI  - Adverse skin reactions to personal protective equipment against severe acute
      respiratory syndrome--a descriptive study in Singapore.
AB  - Severe acute respiratory syndrome (SARS) was first recognized in February 2003.
      It is the first severe and readily transmissible new disease to emerge in the
      21st century. Healthcare workers in affected countries were exposed to the
      regular use of personal protective equipment (PPE) such as the N95 mask, gloves,
      and gowns. Our aim was to study the prevalence of adverse skin reactions to PPE
      among healthcare workers in Singapore during the SARS outbreak. Healthcare staff
      in the National Skin Centre and Tan Tock Seng Hospital were surveyed using
      questionnaires. Of those asked to participate, 322 (94.7%) agreed. 14.3% of the
      respondents were doctors, 73.0% nurses, and 12.7% other ancillary staff. Mean age
      of respondents was 32.4 years, with the majority being women (85.7%) and Chinese
      (53.7%). 109 (35.5%) of the 307 staff who used masks regularly reported acne
      (59.6%), facial itch (51.4%), and rash (35.8%) from N95 mask use. 64 (21.4%) of
      the 299 who used gloves regularly reported dry skin (73.4%), itch (56.3%), and
      rash (37.5%). The use of PPE is associated with high rates of adverse skin
      reactions. There is a need to find suitable alternatives for affected staff and
      to encourage awareness among staff of the role of dermatologists in their care.

PMID- 17026696
TI  - The validity of a questionnaire-based epidemiological study of occupational
      dermatosis.
AB  - The aim of this study was to evaluate the validity of a questionnaire and medical
      anamnesis to identify persons with dermatitis in an occupational setting. The
      design was a clinical epidemiological cross-sectional study. The study was
      performed between the second and fourth week of January 2001. A questionnaire was
      followed a week later by a medical occupational interview and a clinical
      dermatological examination, including a comprehensive patch test with potential
      workplace chemicals. The anamnesis and the clinical examination were made
      independently by occupational and dermatological physicians, and the skin
      examination was performed blinded to anamnestic data. The setting was the mother
      plants of a Danish-based international company producing wind turbine systems.
      The study population was a workplace cohort, highly exposed to epoxy resin
      systems and other chemicals, and totalled 724 production workers at 4 facilities.
      The rate of participation was 84.7%. Using enquete questions of current skin rash
      against the clinical presence of dermatitis, we found a sensitivity of 22% and a
      specificity of 89%, compared to 45% and 87%, respectively, when the anamnestic
      work history, taken by an occupational physician, was the screening parameter.
      Using 'workplace periodic prevalence' of dermatitis, we found sensitivities in
      the range of 63-76% by a questionnaire and 70-83% by medical anamnesis.
      Questionnaire screening by skin symptoms gave the highest values for redness, a
      sensitivity of 33% and a specificity of 76%, and decreasing validity parameters
      as more symptoms were added to the list of screening questions. We found that the
      use of a questionnaire and medical anamnesis were problematic, when the purpose
      was screening for contact dermatitis and allergy, in this industrial cohort
      manufacturing reinforced plastic products. But these instruments might be useful
      for epidemiological surveillance, when the questionnaire has been validated in
      the given occupational setting.

PMID- 17026697
TI  - IgE-mediated anaphylaxis from chlorhexidine: diagnostic possibilities.

PMID- 17026698
TI  - Occupational airborne dermatitis from gordolobo (Verbascum densiflorum).

PMID- 17026699
TI  - Contact allergy to sodium cocoamphoacetate present in an eye make-up remover.
AB  - This is a case report of a contact allergic reaction on the face due to a skin
      cleansing product containing the amphoteric surfactant sodium cocoamphoacetate,
      occurring in an atopic woman with multiple contact sensitivities. Because of its
      weak irritant properties, this surfactant is widely used in cosmetic products
      intended to be used for sensitive skin, including products for intimate, and baby
      hygiene.

PMID- 17026700
TI  - Irritant contact dermatitis with a vasculitic-like pattern from PVP-I.

PMID- 17026701
TI  - Photopatch tests: any news under the sun?

PMID- 17026702
TI  - Contact allergy to propylene glycol and dodecyl gallate mimicking seborrheic
      dermatitis.

PMID- 17026703
TI  - Occupational contact urticaria-dermatitis by Tyrophagus putrescentiae.

PMID- 17026704
TI  - Contact erythema annulare centrifugum.

PMID- 17026705
TI  - PPD: is this a connubial dermatitis?

PMID- 17026706
TI  - Airborne contact dermatitis to methylchloroisothiazolinone/methylisothiazolinone
      in a boy.

PMID- 17026707
TI  - Airborne contact dermatitis from n-alkyl dimethylbenzylammonium chloride and n
      alkyl dimethylethyl-benzylammonium chloride in a detergent.
AB  - Occupational airborne contact dermatitis from disinfectants are not frequent.
      They are usually seen in hospitals, were the exposure is more common. We report a
      case of a young woman, with an intense eczematous eruption that developed hours
      after an accidental contact with a cleaning solution.

PMID- 17026708
TI  - Allergic contact dermatitis from cera alba (purified propolis) in a lip balm and
      candy.

PMID- 17026709
TI  - Both mercaptobenzothiazole and mercapto mix should be part of the standard
      series.

PMID- 17026711
TI  - Somatic H1 histone accumulation and germ layer determination in amphibian
      embryos.
AB  - The induction of mesoderm and/or endoderm from prospective ectoderm and
      dorsalization of the marginal zone mesoderm may be linked to inhibition of cell
      cycling and DNA synthesis in early amphibian embryos. In turn, this may lead to
      reduction of somatic H1 histone accumulation. A greater number of cell cycles and
      rounds of DNA synthesis characterizes the induction of neural tissue. This is
      correlated with an increase of somatic H1 histone accumulation. The number of
      rounds of DNA replication may regulate the level of H1 histone accumulation and
      this may have a role in germ layer determination.

PMID- 17026712
TI  - Sox genes regulate type 2 collagen expression in avian neural crest cells.
AB  - Neural crest cells give rise to a wide variety of cell types, including cartilage
      cells in the cranium and neurons and glial cells in the peripheral nervous
      system. To examine the relationship of cartilage differentiation and neural crest
      differentiation, we examined the expression of Col2a1, which encodes type 2
      collagen often used as a cartilage marker, and compared it with the expression of
      Sox transcription factor genes, which are involved in neural crest development
      and chondrogenesis. We found that Col2a1 is expressed in many neural crest
      derived cell types along with combinations of Sox9, Sox10 and LSox5.
      Overexpression studies reveal the activation of Col2a1 expression by Sox9 and
      Sox10, and cross-regulation of these Sox genes. Luciferase assay indicates a
      direct activation of the Col2a1 enhancer/promoter both by Sox9 and Sox10, and
      this activation is further enhanced by cAMP-dependent kinase (PKA) signaling. Our
      study suggests that the regulatory mechanisms are similar in cartilage and neural
      crest differentiation.

PMID- 17026713
TI  - Endo16 is required for gastrulation in the sea urchin Lytechinus variegatus.
AB  - The Endo16 gene encodes a large extracellular protein with several functional
      domains that provide some insight into the role of this protein during embryonic
      development. We isolated the full-length cDNA sequence from Lytechinus variegatus
      and utilized morpholinos to further investigate the role of Endo16 during
      embryonic development in this species. Endo16-deficient embryos failed to undergo
      gastrulation and the blastocoele became filled with dissociated cells after 24 h
      of incubation. Moreover, there was a delay in endoderm differentiation as assayed
      by staining with an antibody that recognizes Endo1. The differentiation of other
      cell types including oral ectoderm, primary mesenchymal cells (PMC) and secondary
      mesenchymal cells (SMC) appeared to be normal, although the patterns of protein
      expression did not resemble control embryos due to the gross morphological
      abnormalities elicited by the LvEndo16 morpholino. Microinjection of full-length
      EGFP mRNA with the LvEndo16 morpholino-targeted sequence confirmed that this
      phenotype can be attributed specifically to the loss of Endo16 protein. Taken
      together, our data suggest that Endo16 may be required for the cell-extracellular
      matrix (ECM) interactions that are required for endoderm differentiation in the
      sea urchin embryo.

PMID- 17026714
TI  - Characterization of myeloid cells derived from the anterior ventral mesoderm in
      the Xenopus laevis embryo.
AB  - A recent study revealed the presence of a unique population of myeloid cells in
      the anterior ventral (AV) mesoderm of Xenopus laevis embryo, as characterized by
      the expression of peroxidase 2 (POX2), which encodes for a leukocyte-specific
      enzyme. The current report further characterized the POX2-positive cells in terms
      of their contribution to hematopoiesis in tadpole and regulatory mechanism in
      differentiation. Grafting experiments with cytogenetically labeled tissues
      revealed that AV-derived mesoderm supplies a transient population of migrating
      leukocytes in the mesenchyme of early tadpole. These cells were rarely found in
      blood vessels at any stages. Using a ventral marginal zone explant system, we
      demonstrated that dkk1, shown as a heart inducer in this system, has a strong
      ability to induce the expression of POX2. Injection of a high dose dkk1 RNA
      induced a heart marker while a low dose of dkk1 preferentially induced the
      expression of POX2, suggesting that dkk1 works as a morphogen to determine the
      different lineages. Overall results indicate that wnt signal inhibitors induce
      leukocytes at the early neurula stage and that these cells spread to the entire
      body and exist until the ventral blood island-derived leukocytes appear in the
      body.

PMID- 17026715
TI  - Role of ERK 1/2 signaling in neuronal differentiation of cultured embryonic stem
      cells.
AB  - Embryonic stem (ES) cells represent an ideal source for cell engraftment in the
      damaged central nervous system (CNS). Understanding key signals that control ES
      cell differentiation may improve cell type-specific differentiation that is
      suitable for transplantation therapy. We tested the hypothesis that extracellular
      signal-regulated kinase (ERK) 1/2 phosphorylation is an early signaling event
      required for the neuronal differentiation of ES cells. Cultured mouse ES cells
      were treated with an all-trans-retinoic-acid (RA) protocol to generate neurally
      induced progenitor cells. Western blot analysis showed a dramatic increase in ERK
      1/2 phosphorylation (p-ERK 1/2) 1-5 days after RA induction, which was attenuated
      in the presence of the p-ERK 1/2-specific inhibitor UO126. Phospho-ERK 1/2
      inhibition significantly reduced the number of NeuN-positive cells and the
      expression of associated cytoskeletal proteins. In differentiating ES cells,
      there was increased nuclear translocation of STAT3 and decreased protein
      expression levels of GDNF, BDNF and NGF. STAT3 translocation was attenuated by
      UO126. Finally, caspase-3 activation was observed in the presence of UO126,
      suggesting that the ERK pathway also contributes to the survival of
      differentiating ES cells. These data indicate that ERK 1/2 phosphorylation is a
      key event required for early neuronal differentiation and survival of ES cells.

PMID- 17026716
TI  - Functional demonstration of the ability of a primary spermatogonium as a stem
      cell by tracing a single cell destiny in Xenopus laevis.
AB  - In Xenopus, although primary spermatogonium (PG), the largest cell in the testis,
      is believed to be spermatogonial stem cell by histological observations,
      functional evidence has never been obtained. In the present study, we first
      indicated that culture of juvenile testis in a medium supplemented with follicle
      stimulating hormone resulted in no proliferation of PG. In this culture system,
      early secondary spermatogonia could undergo mitotic divisions with a concomitant
      decrease in their size, so that they became distinguishable in size from PG.
      Because the subcutaneous environment of juveniles permitted aggregates of the
      dissociated testicular cells to reconstruct the normal testis structure, we next
      inserted a genetically marked PG isolated from cultured testes into the aggregate
      and transplanted it subcutaneously. In this system, 73.9% of the aggregates
      contained a marked PG. When we observed the aggregates 12 weeks after
      transplantation, most aggregates (70.0%) contained marked PG that had self
      renewed. Among these, fully growing aggregates contained many spermatogenic cells
      at the later developmental stage. These results suggested that isolated PG from
      the cultured testes had the ability as stem cells, and that purification of the
      spermatogenic stem cells became reliable in Xenopus.

PMID- 17026717
TI  - Differential growth identified in salamander larvae half-sib cohorts: survival
      strategy?
AB  - In this study we describe the growth of several different larval cohorts (i.e.
      half-siblings of the same mother born on the same day) of a rare, xeric-adapted
      salamander Salamandra s. infraimmaculata Martens, 1885, under constant density
      and food conditions from birth to metamorphosis. The larvae spend the critical
      first phase of their lives in water, mostly in temporary ponds. Age and weight at
      metamorphosis were highly affected by varying food conditions. We have identified
      six different growth modes that these larvae use, both fast growing and slow
      growing. Each larval cohort was found to use 2-4 different such growth modes
      regardless of their initial weight. Fast growing modes (I-III) will enable larvae
      to survive dry years, and metamorphose bigger. Slow growing modes (IV-VI), used
      by 8% of the larval population, will enable survival only in rainy years. These
      last growth modes effect differential temporal dispersal in wet years by delaying
      the emergence of postmetamorphs onto land. Distribution of growth modes in the
      larval population is affected by food but not by density conditions. Late-born,
      fast-growing larvae will have an advantage in dry years being able to
      metamorphose and disperse, whereas the slow-growing larvae will survive only in
      wet years.

PMID- 17026718
TI  - Dynamics of the IncW genetic backbone imply general trends in conjugative plasmid
      evolution.
AB  - Plasmids cannot be understood as mere tools for genetic exchange: they are
      themselves subject to the forces of evolution. Their genomic and phylogenetic
      features have been less studied in this respect. Focusing on the IncW
      incompatibility group, which includes the smallest known conjugative plasmids, we
      attempt to unveil some common trends in plasmid evolution. The functional modules
      of IncW genetic backbone are described, with emphasis on their architecture and
      relationships to other plasmid groups. Some plasmid regions exhibit strong
      phylogenetic mosaicism, in striking contrast to others of unusual synteny
      conservation. The presence of genes of unknown function that are widely
      distributed in plasmid genomes is also emphasized, exposing the existence of ill
      defined yet conserved plasmid functions. Conjugation is an essential hallmark of
      IncW plasmid biology and special attention is given to the organization and
      evolution of its transfer modules. Genetic exchange between plasmids and their
      hosts is analysed by following the evolution of the type IV secretion system.
      Adaptation of the trw conjugative machinery to pathogenicity functions in
      Bartonella is discussed as an example of how plasmids can change their host modus
      vivendi. Starting from the phage paradigm, our analysis articulates novel
      concepts that apply to plasmid evolution.

PMID- 17026719
TI  - Leishmania cytosolic silent information regulatory protein 2 deacetylase induces
      murine B-cell differentiation and in vivo production of specific antibodies.
AB  - In previous studies, we identified a gene product belonging to the silent
      information regulatory 2 protein (SIR2) family. This protein is expressed by all
      Leishmania species so far examined (L. major, L. infantum, L. amazonensis, L.
      mexicana) and found to be crucial for parasite survival and virulence. In the
      present study, we investigated whether a Leishmania SIR2 recombinant protein
      (LmSIR2) would affect T- and B-cell functions in a murine model. In vitro
      treatment of spleen cells from normal BALB/c mice with LmSIR2 showed increased
      expression of CD69 on B cells. This effect was not abolished by the addition of
      polymyxin B. Intravenous injection of LmSIR2 into BALB/c mice induced increased
      spleen B cell number by a factor of about approximately 1.6, whereas no
      modification occurred at the level of CD4(+) and CD8(+) cells. Furthermore,
      intraperitoneal injection of LmSIR2 alone without adjuvant into BALB/c mice or
      nude mice triggered the production of elevated levels of LmSIR2-specific
      antibodies. The analysis of specific isotype profiles showed a predominance of
      immunoglobulin G1 (IgG1) and IgG2a antibody responses in BALB/c mice, and IgM in
      nude mice. Moreover, the anti-LmSIR2 mouse antibodies in the presence of
      complement induced the in vitro lysis of L. infantum amastigotes. In the absence
      of complement, the antibodies induced significant inhibition of amastigotes
      developpement inside macrophages. Together, the current study provides the first
      evidence that a Leishmania protein belonging to the SIR2 family may play a role
      in the regulation of immune response through its capacity to trigger B-cell
      effector function.

PMID- 17026720
TI  - Comparison of cervical and blood T-cell responses to human papillomavirus-16 in
      women with human papillomavirus-associated cervical intraepithelial neoplasia.
AB  - Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically
      cause localized mucosal infections. We therefore hypothesized that T-cell
      responses to HPV antigens would be greater at sites of pathology than in the
      blood. Focusing on HPV-16 because of its association with cervical cancer, the
      magnitude of HPV-specific T-cell responses at the cervix was compared with those
      in the peripheral blood by intracellular cytokine staining following direct ex
      vivo stimulation with both virus-like particles assembled from the major capsid
      protein L1, and the major HPV oncoprotein, E7. We show that both CD4(+) and
      CD8(+) T cells from the cervix responded to the HPV-16 antigens and that
      interferon-gamma (IFN-gamma) production was HPV type-specific. Comparing HPV
      specific T-cell IFN-gamma responses at the cervix with those in the blood, we
      found that while CD4(+) and CD8(+) T-cell responses to L1 were significantly
      correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-gamma
      responses in both T-cell subsets were significantly greater in magnitude at the
      cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In
      contrast, both CD4(+) and CD8(+) T-cell IFN-gamma responses to E7 were of similar
      magnitude in both compartments and CD8(+) responses were significantly correlated
      between these distinct immunological compartments (P = 0.04). We therefore show
      that inflammatory T-cell responses against L1 (but not E7) demonstrate clear
      compartmental bias and the magnitude of these responses do reflect local viral
      replication but that correlation of HPV-specific responses between compartments
      indicates their linkage.

PMID- 17026721
TI  - Recombinant integrin CD11b A-domain blocks polymorphonuclear cells recruitment
      and protects against skeletal muscle inflammatory injury in the rat.
AB  - The beta2 integrin CD11b/CD18 (CR3) is a major adhesion receptor of neutrophils,
      normally utilized to fend off infections. This receptor contributes, however, to
      multiple forms of non-infectious inflammatory injury when dysregulated as shown
      in gene knock-outs and through the use of blocking monoclonal antibodies. The
      major ligand recognition site of CR3 has been mapped to the A-domain in the CD11b
      subunit (CD11bA). The recombinant form of this domain exhibits a ligand binding
      profile similar to that of the holoreceptor. To assess the potential anti
      inflammatory activity of CD11bA as a competitive antagonist of CR3 in vivo, we
      assessed its effects on a developed animal model of traumatic skeletal muscle
      injury in the rat. Recombinant soluble rat CD11bA-domain fused to glutathione-S
      transferase (GST) was administered intravenously in a single dose at 1 mg/kg to
      nine groups of Wistar rats, five in each group, 30 min before inducing traumatic
      skeletal muscle injury. Control animals received either a function-blocking anti
      CD11b/CD18 monoclonal antibody (1 mg/kg), non-functional mutant forms of the
      CD11bA (D140GS/AGA, T209/A, D242/A), recombinant GST or buffer alone. In control
      animals, the wounded muscle showed oedema, erythrocyte extravasation and
      myonecrosis both within and outside the immediate wounded area (5-10 mm zone) and
      influx of neutrophils was detected 30 min post-wound, followed by a second wave 3
      hr later. Wild-type CD11bA- or anti-CD11b monoclonal antibody (mAb)-treated rats
      showed a comparable and significant decrease in the number of infiltrating PMN
      (78 + 4%, n = 70 and 86 +/- 2%, n = 50, respectively) and preservation of the
      muscular fibres outside the immediate zone of necrosis (75 + 4%, n = 70, 84 +/-
      1%, n = 50, respectively), compared to controls. These data demonstrate that
      CD11bA can be an effective tissue-preserving agent in acute inflammatory muscular
      injury.

PMID- 17026722
TI  - The value of urine specific gravity in detecting diabetes insipidus in a patient
      with uncontrolled diabetes mellitus: urine specific gravity in differential
      diagnosis.
AB  - When a patient with diabetes mellitus presents with worsening polyuria and
      polydipsia, what is a sensible, cost-effective approach? We report the unique
      coincidence of type 2 diabetes mellitus and diabetes insipidus. A 46-year-old
      woman with poorly controlled type 2 diabetes complained of polyuria with a daily
      output of 5 L. Although urinalysis demonstrated significant glucosuria, diabetes
      insipidus was suspected owing to a low urine specific gravity (1.008). The low
      specific gravity persisted during a water deprivation test. Ultimately, diabetes
      insipidus was confirmed when urine specific gravity and urine osmolality
      normalized following desmopressin administration. This case emphasizes the
      importance of accurately interpreting the urine specific gravity in patients with
      polyuria and diabetes mellitus to detect diabetes insipidus.

PMID- 17026723
TI  - Acquired Fanconi's syndrome associated with tenofovir therapy.
AB  - Tenofovir (Viread) is a nucleotide reverse transcriptase inhibitor introduced
      into the United States in 2001. It is frequently prescribed not only for its
      efficacy but also for its decreased side effect profile compared with other
      nucleoside analogs. It is now increasingly recognized as a cause of acquired
      Fanconi's syndrome (FS) in human immunodeficient individuals. We describe a case
      of a patient with AIDS, who, after starting tenofovir therapy, developed
      myalgias, renal failure, and profound electrolyte abnormalities compatible with
      the classic features of FS. On discontinuation of tenofovir and replacement of
      electrolytes, the individual improved clinically with normalization of his renal
      failure and electrolyte abnormalities. With the success of tenofovir in the anti
      HIV drug market, practitioners should remain alert to the possibility of the
      development of FS. Frequent urine, renal, and electrolyte parameters should be
      measured at regular intervals following initiation of tenofovir therapy.

PMID- 17026724
TI  - Disseminated intravascular coagulation as the presenting sign of metastatic
      prostate cancer.
AB  - Disseminated intravascular coagulation (DIC) is an acquired coagulation disorder
      that may occur in a wide variety of clinical conditions. Suspicion of DIC should
      lead to a differential diagnosis that includes primary fibrinolysis and other
      bleeding diatheses such as thrombocytopenias of diverse etiology. Confirmation of
      the diagnosis of DIC should always prompt a search for an underlying medical
      disorder, including sepsis, severe trauma, solid and hematological malignancies,
      obstetrical complications, and vascular disorders. Here, we describe an unusual
      case of acute bleeding and DIC as the presenting manifestation of metastatic
      prostate cancer in a 60-year-old man. Treatment with a luteinizing hormone
      releasing hormone (LHRH) agonist and a short course of an antiandrogen, together
      with supportive measures (i.e., clotting factors, heparin, and platelets), led to
      normalization of all coagulation parameters within 1 week, and to clinical
      improvement and decline in the serum level of prostate-specific antigen (PSA). We
      discuss the pathogenesis, differential diagnosis, and association of DIC with
      prostate cancer along with the management of this condition.

PMID- 17026725
TI  - A twist on torsade: a prolonged QT interval on methadone.
AB  - A woman developed a prolonged QT interval and torsade de pointes while on
      methadone treatment for heroin addiction. We think methadone, or its impaired
      metabolism, was the major cause for her prolonged QT interval and progression to
      torsade. However, torsade is often multifactorial, as was likely so in this case.
      We advise physicians treating patients taking methadone to obtain careful
      medication and drug-use histories, screen for risk factors associated with long
      QT syndrome, counsel patients about potential drug interactions, and measure the
      QT interval before and during methadone treatment in high-risk patients.

PMID- 17026726
TI  - Medical comorbidity in women and men with schizophrenia: a population-based
      controlled study.
AB  - BACKGROUND: Persons with persistent mental illness are at risk for failure to
      receive medical services. In order to deliver appropriate preventive and primary
      care for this population, it is important to determine which chronic medical
      conditions are most common. OBJECTIVE: We examined chronic medical comorbidity in
      persons with schizophrenia using validated methodologies. DESIGN: Retrospective
      analysis of longitudinal administrative claims data from Wellmark Blue Cross/Blue
      Shield of Iowa. PARTICIPANTS: Subjects with schizophrenia or schizoaffective
      disorder (N=1,074), and controls (N=726,262) who filed at least 1 claim for
      medical services, 1996 to 2001. MEASUREMENTS: Case subjects had schizophrenia as
      the most clinically predominant psychotic disorder, based on psychiatric
      hospitalization, psychiatrist diagnoses, and outpatient care. Controls had no
      claims for any psychiatric comorbidity. Using a modified version of the
      Elixhauser Comorbidity Index, inpatient and outpatient claims were used to
      determine the prevalence of 46 common medical conditions. Odds ratios (ORs) were
      adjusted for age, gender, residence, and nonmental health care utilization using
      logistic regression. RESULTS: Subjects with schizophrenia were significantly more
      likely to have 1 or more chronic conditions compared with controls. Adjusted OR
      (95% confidence interval [CI]) were 2.62 (2.09 to 3.28) for hypothyroidism, 1.88
      (1.51 to 2.32) for chronic obstructive pulmonary disease, 2.11 (1.36 to 3.28) for
      diabetes with complications, 7.54 (3.55 to 15.99) for hepatitis C, 4.21 (3.25 to
      5.44) for fluid/electrolyte disorders, and 2.77 (2.23 to 3.44) for nicotine
      abuse/dependence. CONCLUSIONS: Schizophrenia is associated with substantial
      chronic medical burden. Familiarity with conditions affecting persons with
      schizophrenia may assist programs aimed at providing medical care for the
      mentally ill.

PMID- 17026727
TI  - Types of information physicians provide when prescribing antidepressants.
AB  - BACKGROUND: Providing antidepressant information to patients may foster greater
      adherence to therapy. OBJECTIVE: To assess physician information-giving while
      prescribing antidepressants, and to identify factors that influence the provision
      of information. DESIGN: Randomized experiment using standardized patients (SPs).
      Standardized patients roles were generated by crossing 2 clinical conditions
      (major depression or adjustment disorder) with 3 medication request types (brand
      specific, general, or none). PARTICIPANTS: One hundred and fifty-two general
      internists and family physicians recruited from solo and group practices and
      health maintenance organizations; cooperation rates ranged from 53% to 61%.
      MEASUREMENTS: We assessed physician information-giving by analyzing audio
      recordings of interactions between physicians and SPs, and collected physician
      background information by survey. Generalized estimating equations were used to
      examine the influence of patient and physician factors on physicians' provision
      of information. RESULTS: One hundred and one physicians prescribed
      antidepressants, accounting for 131 interactions. The mean age of physicians was
      46.3 years; 69% were males. Physicians mentioned an average of 5.7 specific
      topics of antidepressant-related information (of a possible maximum of 11). The
      most frequently mentioned topic was purpose (96.1%). Physicians infrequently
      provided information about the duration of therapy (34.9%) and costs (21.4%).
      Standardized patients who presented with major depression received less
      information than those with adjustment disorder, and older and solo/private
      practice physicians provided significantly less information to SPs. CONCLUSIONS:
      Physicians provide limited information to patients while prescribing
      antidepressants, often omitting critical information that may promote adherence.
      Mechanisms are needed to ensure that patients receive pertinent antidepressant
      information.

PMID- 17026728
TI  - Brief report: incidence, etiology, risk factors, and outcome of hospital-acquired
      fever: a systematic, evidence-based review.
AB  - OBJECTIVES: Temperature is universally measured in the hospitalized patient, but
      the literature on hospital-acquired fever has not been systematically reviewed.
      This systematic review is intended to provide clinicians with an overview of the
      incidence, etiology, and outcome of hospital-acquired fever. DATA SOURCES: We
      searched MEDLINE (1970 to 2005), EMBASE (1988 to 2004), and Web of Knowledge.
      References of all included articles were reviewed. Articles that focused on
      children, fever in the developing world, classic fever of unknown origin, or
      specialized patient populations were excluded. REVIEW METHODS: Articles were
      reviewed independently by 2 authors before inclusion; a third author acted as
      arbiter. RESULTS: Of over 1,000 studies reviewed, 7 met the criteria for
      inclusion. The incidence of hospital-acquired fever ranged from 2% to 17%. The
      etiology of fever was infection in 37% to 74%. Rates of antibiotic use for
      patients with a noninfectious cause of fever ranged from 29% to 55% for a mean
      duration of 6.6 to 9.6 days. Studies varied widely in their methodology and the
      patient population studied. CONCLUSIONS: Limited information is available to
      guide an evidence-based approach to hospital-acquired fever. We propose criteria
      to help standardize future studies of this important clinical situation.

PMID- 17026729
TI  - Morbidity and mortality conference, grand rounds, and the ACGME's core
      competencies.
AB  - Morbidity and Mortality (M&M) Conferences are an Accreditation Council for
      Graduate Medical Education (ACGME) mandated educational series that occur
      regularly at all institutions that have residency training programs. The
      potential for learning from medical errors, complications, and unanticipated
      outcomes is immense--provided that the focus is on education, as opposed to
      culpability. The education innovation described in this manuscript is the manner
      in which we have used the ACGME Outcome Project's 6 core competencies as the
      structure upon which the cases discussed at our M&M conference are framed. When
      presented at grand rounds in a novel format, M&M conference has not only
      maintained support for the quality improvement efforts in the Department, but has
      served to improve the educational impact of the conference.

PMID- 17026730
TI  - Exploring the educational value of clinical vignettes from the Society of General
      Internal Medicine national meeting in the internal medicine clerkship: a pilot
      study.
AB  - INTRODUCTION: Whether the clinical vignettes presented at the Society of General
      Internal Medicine (SGIM) annual meeting could be of educational value to third
      year students in the Internal Medicine clerkship has not been studied. OBJECTIVE:
      To explore the relevance and learning value of clinical vignettes from the SGIM
      national meeting in the Internal Medicine clerkship. SETTING: Third year
      Ambulatory Internal Medicine clerkship at one academic medical center (academic
      year 2005 to 2006). METHODS: Students were introduced to the clinical vignette
      and oriented to the database of clinical vignettes available through the SGIM
      annual meeting website. Students then reviewed 5 to 10 clinical vignettes using a
      worksheet, and rated the learning value of each vignette using a 5-point Likert
      scale (1=least, 5=greatest). A single investigator evaluated congruence of the
      vignette with the Clerkship Directors of Internal Medicine (CDIM)-SGIM curriculum
      to assess relevance. MAIN RESULTS: A total of 42 students evaluated 371 clinical
      vignettes from the 2004 and 2005 meetings. The clinical vignettes were curriculum
      congruent in 42.6% (n=175), and clearly incongruent in 40.4% (n=164). The mean
      rating for learning value was 3.8 (+/-1.0) (5 signifying greatest learning
      value). Curriculum-congruent vignettes had a higher mean learning value compared
      with curriculum-incongruent vignettes (4.0 vs 3.6, Student's t-test, P=.017).
      CONCLUSION: The clinical vignettes presented at the national SGIM meeting offer
      clinical content that is relevant and of some educational value for third year
      clerkship students. Based on this pilot study, the educational value and
      strategies for their use in the clinical clerkships deserve further study.

PMID- 17026731
TI  - The effect of market reform on racial differences in hospital mortality.
AB  - OBJECTIVE: To determine whether racial differences in hospital mortality worsened
      after implementation of a New Jersey law in 1993 that reduced subsidies for
      uninsured hospital care and changed hospital payment from rate regulation to
      price competition. DATA SOURCES/STUDY SETTING: State discharge data for New
      Jersey and New York from 1990 to 1996. STUDY DESIGN: We used an interrupted time
      series design to compare risk-adjusted in-hospital mortality rates between states
      over time. Adjusting for patient characteristics, baseline interstate
      differences, and common intertemporal trends, we compared the effect sizes for
      whites and blacks in the following 4 groups: overall, uninsured, insured under
      age 65, and Medicare patients. DATA COLLECTION/EXTRACTION METHODS: The study
      sample included 1,357,394 patients admitted to New Jersey or New York hospitals
      between 1990 to 1996 with stroke, hip fracture, pneumonia, pulmonary embolism,
      congestive heart failure, or acute myocardial infarction (AMI). PRINCIPAL
      FINDINGS: The increase in mortality in New Jersey versus New York was
      significantly larger among blacks than among whites for AMI (2.4% points vs 0.1%
      points, P-value for difference .026) but not for the other 6 conditions. In
      groupings of conditions for which hospital admission is non-discretionary and
      conditions in which admission is discretionary, we found qualitatively larger
      increases in mortality for blacks but no statistically significant racial
      differences among patients overall, uninsured patients, insured patients under
      age 65, or Medicare patients. CONCLUSIONS: Market-based reform and reductions in
      subsidies for hospital care for the uninsured in New Jersey were associated with
      worsening racial disparities in in-hospital mortality for AMI but not for 6 other
      common conditions.

PMID- 17026735
TI  - Medical care for patients with severe and persistent mental illness.

PMID- 17026736
TI  - Tough questions, even harder answers.

PMID- 17026737
TI  - The inherent inequities of market-based health care reform.

PMID- 17026739
TI  - Letter to the editor regarding Kho, et al.

PMID- 17026741
TI  - Internal medicine specialists' attitudes towards working part-time: a comparison
      between 1996 and 2004.
AB  - BACKGROUND: Although medical specialists traditionally hold negative views
      towards working part-time, the practice of medicine has evolved. Given the trend
      towards more part-time work and that there is no evidence that it compromises the
      quality of care, attitudes towards part-time work may have changed as well in
      recent years. The aim of this paper was to examine the possible changes in
      attitudes towards part-time work among specialists in internal medicine between
      1996 and 2004. Moreover, we wanted to determine whether these attitudes were
      associated with individual characteristics (age, gender, investments in work) and
      whether attitudes of specialists within a partnership showed more resemblance
      than specialists' attitudes from different partnerships. METHODS: Two samples
      were used in this study: data of a survey conducted in 1996 and in 2004. After
      selecting internal medicine specialists working in general hospitals in The
      Netherlands, the sample consisted of 219 specialists in 1996 and 363 specialists
      in 2004. They were sent a questionnaire, including topics on the attitudes
      towards part-time work. RESULTS: Internal medicine specialists' attitudes towards
      working part-time became slightly more positive between 1996 and 2004. Full-time
      working specialists in 2004 still expressed concerns regarding the investments of
      part-timers in overhead tasks, the flexibility of task division, efficiency,
      communication and continuity of care. In 1996 gender was the only predictor of
      the attitude, in 2004 being a full- or a part-timer, age and the time invested in
      work were associated with this attitude. Furthermore, specialists' attitudes were
      not found to cluster much within partnerships. CONCLUSION: In spite of the
      increasing number of specialists working or preferring to work part-time, part
      time practice among internal medicine specialists seems not to be fully accepted.
      The results indicate that the attitudes are no longer gender based, but are
      associated with age and work aspects such as the number of hours worked. Though
      there is little evidence to support them, negative ideas about the consequences
      of part-time work for the quality of care still exist. Policy should be aimed at
      removing the organisational difficulties related to part-time work and create a
      system in which part-time practice is fully integrated and accepted.

PMID- 17026740
TI  - Clinicopathological significance of stromal variables: angiogenesis,
      lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal
      carcinomas.
AB  - Cancer research has mainly focused on alterations of genes and proteins in cancer
      cells themselves that result in either gain-of-function in oncogenes or loss-of
      function in tumour-suppressor genes. However, stromal variables within or around
      tumours, including blood and lymph vessels, stromal cells and various proteins,
      have also important impacts on tumour development and progression. It has been
      shown that disruption of stromal-epithelial interactions influences cellular
      proliferation, differentiation, death, motility, genomic integrity, angiogenesis,
      and other phenotypes in various tissues. Moreover, stromal variables are also
      critical to therapy in cancer patients. In this review, we mainly focus on the
      clinicopathological significance of stromal variables including angiogenesis,
      lymphangiogenesis, inflammatory infiltration, matrix metalloproteinase (MMP), and
      the particularly interesting new cysteine-histidine rich protein (PINCH) in
      colorectal cancer (CRC).

PMID- 17026743
TI  - Trends in scientific activity addressing transmissible spongiform
      encephalopathies: a bibliometric study covering the period 1973-2002.
AB  - BACKGROUND: The purpose of this study is to analyse the trends in scientific
      research on transmissible spongiform encephalopathies by applying bibliometric
      tools to the scientific literature published between 1973 and 2002. METHODS: The
      data for the study were obtained from Medline database, in order to determine the
      volume of scientific output in the above period, the countries involved, the type
      of document and the trends in the subject matters addressed. The period 1973-2002
      was divided in three sub-periods. RESULTS: We observed a significant growth in
      scientific production. The percentage of increase is 871.7 from 1973 to 2002.
      This is more evident since 1991 and particularly in the 1996-2001 period. The
      countries found to have the highest output were the United States, the United
      Kingdom, Japan, France and Germany. The evolution in the subject matters was
      almost constant in the three sub-periods in which the study was divided. In the
      first and second sub-periods, the subject matters of greatest interest were more
      general, i.e Nervous system or Nervous system diseases, Creutzfeldt-Jakob
      disease, Scrapie, and Chemicals and Drugs, but in the last sub-period, some
      changes were observed because the Prion-related matters had the greatest
      presence. Collaboration among authors is small from 1973 to 1992, but increases
      notably in the third sub-period, and also the number of authors and clusters
      formed. Some of the authors, like Gajdusek or Prusiner, appear in the whole
      period. CONCLUSION: The study reveals a very high increase in scientific
      production. It is related also with the beginnings of research on bovine
      spongiform encephalopathy and variant Creutzfeldt-Jakob disease, with the
      establishment of progressive collaboration relationships and a reflection of
      public health concerns about this problem.

PMID- 17026744
TI  - [X]uniqMAP: unique gene sequence regions in the human and mouse genomes.
AB  - BACKGROUND: Current approaches for genome-wise functional analyses, such as
      microarray and RNA interference studies, rely on the specificity of
      oligonucleotide sequences to selectively target cellular transcripts. The design
      of specific oligos involves the determination of unique DNA regions in the
      gene/transcripts of interest from the targeted organism. This process is tedious,
      time consuming and it does not scale up for high-throughput studies. DESCRIPTION:
      Taking advantage of the availability of complete genome sequence information for
      mouse and human, the most widely used systems for the study of mammalian
      genetics, we have built a database, [X]uniqMAP, that stores the precalculated
      unique regions for all transcripts of these two organisms. For each gene, the
      database discriminates between those unique regions that are shared by all
      transcripts and those exclusive to single transcripts. In addition, it also
      provides those unique regions that are shared between orthologous genes from the
      two organisms. The database is updated regularly to reflect changes in genome
      assemblies and gene builds. CONCLUSION: Over 85% of genes have unique regions at
      least 19 bases long, with the majority being unique over 60% of their lengths.
      14482 human genes share exactly at least a unique region with mouse genes, though
      such regions are typically under 40 bases long. The full data are publicly
      accessible online both interactively and for download. They should facilitate (i)
      the design of probes, primers and siRNAs for both small- and large-scale
      projects; and (ii) the identification of regions for the design of oligos that
      could be re-used to target equivalent gene/transcripts from human and mouse.

PMID- 17026742
TI  - Hyper-IgG4 disease: report and characterisation of a new disease.
AB  - BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4
      disease', which has many synonyms depending on the organ involved, the country of
      origin and the year of the report. It is characterized histologically by a
      lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis,
      which leaves dense fibrosis on resolution. A typical example is idiopathic
      retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing
      pancreatitis. METHODS: We report an index case with fever and severe systemic
      disease. We have also reviewed the histology of 11 further patients with
      idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells,
      and examined a wide range of other inflammatory conditions and fibrotic diseases
      as organ-specific controls. We have reviewed the published literature for disease
      associations with idiopathic, systemic fibrosing conditions and the synonyms:
      pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis,
      xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from
      all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell
      infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes
      eosinophilic aggregates, with venulitis and obliterative arteritis. The majority
      of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell
      rich small lymphoid follicles. In all cases, there was a significant increase in
      IgG4-positive plasma cells compared with controls. In two cases, biopsies before
      and after steroid treatment were available, and only scattered plasma cells were
      seen after treatment, none of them expressing IgG4. Review of the literature
      shows that although pathology commonly appears confined to one organ, patients
      can have systemic symptoms and fever. In the active period, there is an acute
      phase response with a high serum concentration of IgG, and during this phase,
      there is a rapid clinical response to glucocorticoid steroid treatment.
      CONCLUSION: We believe that hyper-IgG4 disease is an important condition to
      recognise, as the diagnosis can be readily verified and the outcome with
      treatment is very good.

PMID- 17026745
TI  - Dog Y chromosomal DNA sequence: identification, sequencing and SNP discovery.
AB  - BACKGROUND: Population genetic studies of dogs have so far mainly been based on
      analysis of mitochondrial DNA, describing only the history of female dogs. To get
      a picture of the male history, as well as a second independent marker, there is a
      need for studies of biallelic Y-chromosome polymorphisms. However, there are no
      biallelic polymorphisms reported, and only 3200 bp of non-repetitive dog Y
      chromosome sequence deposited in GenBank, necessitating the identification of dog
      Y chromosome sequence and the search for polymorphisms therein. The genome has
      been only partially sequenced for one male dog, disallowing mapping of the
      sequence into specific chromosomes. However, by comparing the male genome
      sequence to the complete female dog genome sequence, candidate Y-chromosome
      sequence may be identified by exclusion. RESULTS: The male dog genome sequence
      was analysed by Blast search against the human genome to identify sequences with
      a best match to the human Y chromosome and to the female dog genome to identify
      those absent in the female genome. Candidate sequences were then tested for male
      specificity by PCR of five male and five female dogs. 32 sequences from the male
      genome, with a total length of 24 kbp, were identified as male specific, based on
      a match to the human Y chromosome, absence in the female dog genome and male
      specific PCR results. 14437 bp were then sequenced for 10 male dogs originating
      from Europe, Southwest Asia, Siberia, East Asia, Africa and America. Nine
      haplotypes were found, which were defined by 14 substitutions. The genetic
      distance between the haplotypes indicates that they originate from at least five
      wolf haplotypes. There was no obvious trend in the geographic distribution of the
      haplotypes. CONCLUSION: We have identified 24159 bp of dog Y-chromosome sequence
      to be used for population genetic studies. We sequenced 14437 bp in a worldwide
      collection of dogs, identifying 14 SNPs for future SNP analyses, and giving a
      first description of the dog Y-chromosome phylogeny.

PMID- 17026746
TI  - The SNARE protein family of Leishmania major.
AB  - BACKGROUND: Leishmania major is a protozoan parasite with a highly polarised cell
      shape that depends upon endocytosis and exocytosis from a single area of the
      plasma membrane, the flagellar pocket. SNAREs (soluble N-ethylmaleimide-sensitive
      factor adaptor proteins receptors) are key components of the intracellular
      vesicle-mediated transports that take place in all eukaryotic cells. They are
      membrane-bound proteins that facilitate the docking and fusion of vesicles with
      organelles. The recent availability of the genome sequence of L. major has
      allowed us to assess the complement of SNAREs in the parasite and to investigate
      their location in comparison with metazoans. RESULTS: Bioinformatic searches of
      the L. major genome revealed a total of 27 SNARE domain-containing proteins that
      could be classified in structural groups by phylogenetic analysis. 25 of these
      possessed the expected features of functional SNAREs, whereas the other two could
      represent kinetoplastid-specific proteins that might act as regulators of the
      SNARE complexes. Other differences of Leishmania SNAREs were the absence of
      double SNARE domain-containing and of the brevin classes of these proteins.
      Members of the Qa group of Leishmania SNAREs showed differential expressions
      profiles in the two main parasite forms whereas their GFP-tagging and in vivo
      expression revealed localisations in the Golgi, late endosome/lysosome and near
      the flagellar pocket. CONCLUSION: The early-branching eukaryote L. major
      apparently possess a SNARE repertoire that equals in number the one of metazoans
      such as Drosophila, showing that the machinery for vesicle fusion is well
      conserved throughout the eukaryotes. However, the analysis revealed the absence
      of certain types of SNAREs found in metazoans and yeast, while suggesting the
      presence of original SNAREs as well as others with unusual localisation. This
      study also presented the intracellular localisation of the L. major SNAREs from
      the Qa group and reveals that these proteins could be useful as organelle markers
      in this parasitic protozoon.

PMID- 17026747
TI  - ORENZA: a web resource for studying ORphan ENZyme activities.
AB  - BACKGROUND: Despite the current availability of several hundreds of thousands of
      amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined
      by the Nomenclature Committee of the International Union of Biochemistry and
      Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in
      major public databases. This wide gap separating knowledge of biochemical
      function and sequence information is found for nearly all classes of enzymes.
      Thus, there is an urgent need to explore these sequence-less EC numbers, in order
      to progressively close this gap. DESCRIPTION: We designed ORENZA, a PostgreSQL
      database of ORphan ENZyme Activities, to collate information about the EC numbers
      defined by the NC-IUBMB with specific emphasis on orphan enzyme activities.
      Complete lists of all EC numbers and of orphan EC numbers are available and will
      be periodically updated. ORENZA allows one to browse the complete list of EC
      numbers or the subset associated with orphan enzymes or to query a specific EC
      number, an enzyme name or a species name for those interested in particular
      organisms. It is possible to search ORENZA for the different biochemical
      properties of the defined enzymes, the metabolic pathways in which they
      participate, the taxonomic data of the organisms whose genomes encode them, and
      many other features. The association of an enzyme activity with an amino acid
      sequence is clearly underlined, making it easy to identify at once the orphan
      enzyme activities. Interactive publishing of suggestions by the community would
      provide expert evidence for re-annotation of orphan EC numbers in public
      databases. CONCLUSION: ORENZA is a Web resource designed to progressively bridge
      the unwanted gap between function (enzyme activities) and sequence (dataset
      present in public databases). ORENZA should increase interactions between
      communities of biochemists and of genomicists. This is expected to reduce the
      number of orphan enzyme activities by allocating gene sequences to the relevant
      enzymes.

PMID- 17026748
TI  - Management of plant species for controlling pests, by peasant farmers at Lagoa
      Seca, Paraiba state, Brazil: an ethnoecological approach.
AB  - Ethnoecological knowledge may be understood as spontaneous knowledge, culturally
      referenced of any society's members, learned and transmitted through social
      interactions and that are targeted at resolution of daily routine situations. The
      traditional knowledge in small scale economy societies as well as the non
      academic knowledge in urban-industrial societies might be included in this
      concept. An ethnoecological approach study was performed here on people living at
      the communities of Alvinho, Almeida, Cha do Marinho, Floriano, and Cha de Oiti,
      all located in the municipality of Lagoa Seca, Paraiba state, Northeast Brazil.
      The general objective pursued here was to study the knowledge that peasant
      farmers have on management of plant species utilized for pest control. For this,
      the methodological instruments employed here to investigate the ethnoecological
      knowledge were: direct observation, structured and semi-structured interviews,
      and tours conducted by local peasant farmers. We analyzed the data obtained under
      an emic/etic view and also by comparing the local knowledge with those obtained
      from the literature. The results showed that people in those communities utilize
      management alternatives for controlling pests, which are mainly: (i) fallowing;
      (ii) crop rotation; (iii) destruction of crop remains and fruits attacked by
      pests; (iv) alternations of crops with repellent plants; and/or (v) mixed
      cropping; (vi) insect's larvae covered with soil; (vii) crops irrigated
      abundantly; and (viii) soil preparation. The recovery and comprehension we get
      about this knowledge as well as the farmers' savoir faire, are extremely
      important to the revival of ancient agricultural practices, which have been
      forgotten due to advances in modern agriculture. The data obtained here showed
      that a huge body of knowledge the farmers have on many forms or strategies of
      management are generally compatible with scientific knowledge.

PMID- 17026749
TI  - Double valve replacement for acute spontaneous left chordal rupture secondary to
      chronic aortic incompetence.
AB  - A 54 years old male with undiagnosed chronic calcific degenerative aortic valve
      incompetence presented with acute left anterior chordae tendinae rupture
      resulting in severe left heart failure and cardiogenic shock. He was successfully
      treated with emergency double valve replacement using mechanical valves. The
      pathogenesis of acute rupture of the anterior chordae tendinae, without any
      evidence of infective endocarditis or ischemic heart disease seems to have been
      attrition of the subvalvular mitral apparatus by the chronic regurgitant jet of
      aortic incompetence with chronic volume overload. We review the literature with
      specific focus on the occurrence of this unusual event.

PMID- 17026750
TI  - Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men
      and women.
AB  - BACKGROUND: Cigarette smoking is an established risk factor for bladder cancer.
      Epidemiological and biological data suggest that genetic polymorphisms in
      activating and detoxifying enzymes may play a role in determining an individual's
      susceptibility to bladder cancer in particular when in combination with specific
      environmental exposures such as cigarette smoking. N-acetyltransferase (NAT)
      enzymes, NAT1 and NAT2, are involved in the activation and detoxification of
      tobacco smoke constituents. Polymorphisms in these genes alter the ability of
      these enzymes to metabolize carcinogens, as certain allelic combinations result
      in a slow or rapid acetylation phenotype. Glutathione S-transferases (GSTs) also
      detoxify tobacco smoke constituents, and polymorphisms within the GSTM1 and GSTT1
      genes can result in a complete lack of enzyme activity. METHODS: We assessed the
      association between common polymorphisms identified in the GSTM1, GSTT1, NAT1,
      and NAT2 genes and the risk of bladder cancer in two nested case-control studies
      within the Nurses' Health Study (n = 78 female cases, 234 female controls) and
      the Health Professionals' Follow-up Study (n = 139 male cases, 293 male
      controls). We also evaluated whether cigarette smoking modified the associations
      of the genotypes and bladder cancer risk in men and women. RESULTS: Overall, we
      observed no statistically significant associations between the polymorphisms and
      bladder cancer risk among men and women, although given our sample size, we had
      limited power to detect small to moderate effects. There was however the
      suggestion of an increased risk among female ever smokers with the NAT2 slow
      genotype and an increased risk in male never smokers with the GSTM1 null
      genotype. CONCLUSION: In summary, these prospective results are consistent with
      previous literature supporting associations between bladder cancer and the NAT2
      slow acetylation and the GSTM1 null genotypes.

PMID- 17026751
TI  - A super-spreading ewe infects hundreds with Q fever at a farmers' market in
      Germany.
AB  - BACKGROUND: In May 2003 the Soest County Health Department was informed of an
      unusually large number of patients hospitalized with atypical pneumonia. METHODS:
      In exploratory interviews patients mentioned having visited a farmers' market
      where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever.
      We asked local health departments in Germany to identify notified Q fever
      patients who had visited the farmers market. To investigate risk factors for
      infection we conducted a case control study (cases were Q fever patients,
      controls were randomly selected Soest citizens) and a cohort study among vendors
      at the market. The sheep exhibited at the market, the herd from which it
      originated as well as sheep from herds held in the vicinity of Soest were tested
      for Coxiella burnetii (C. burnetii). RESULTS: A total of 299 reported Q fever
      cases was linked to this outbreak. The mean incubation period was 21 days, with
      an interquartile range of 16-24 days. The case control study identified close
      proximity to and stopping for at least a few seconds at the sheep's pen as
      significant risk factors. Vendors within approximately 6 meters of the sheep's
      pen were at increased risk for disease compared to those located farther away.
      Wind played no significant role. The clinical attack rate of adults and children
      was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The
      ewe that had lambed as well as 25% of its herd tested positive for C. burnetii
      antibodies. CONCLUSION: Due to its size and point source nature this outbreak
      permitted assessment of fundamental, but seldom studied epidemiological
      parameters. As a consequence of this outbreak, it was recommended that pregnant
      sheep not be displayed in public during the 3rd trimester and to test animals in
      petting zoos regularly for C. burnetii.

PMID- 17026752
TI  - Evaluation of the acquired immune responses to Plasmodium vivax VIR variant
      antigens in individuals living in malaria-endemic areas of Brazil.
AB  - BACKGROUND: The naturally-acquired immune response to Plasmodium vivax variant
      antigens (VIR) was evaluated in individuals exposed to malaria and living in
      different endemic areas for malaria in the north of Brazil. METHODS: Seven
      recombinant proteins representing four vir subfamilies (A, B, C, and E) obtained
      from a single patient from the Amazon Region were expressed in Escherichia coli
      as soluble glutathione S-transferase fusion proteins. The different recombinant
      proteins were compared by ELISA with regard to the recognition by IgM, IgG, and
      IgG subclass of antibodies from 200 individuals with patent infection. RESULTS:
      The frequency of individuals that presented antibodies anti-VIR (IgM plus IgG)
      during the infection was 49%. The frequencies of individuals that presented IgM
      or IgG antibodies anti-VIR were 29.6% or 26.0%, respectively. The prevalence of
      IgG antibodies against recombinant VIR proteins was significantly lower than the
      prevalence of antibodies against the recombinant proteins representing two
      surface antigens of merozoites of P. vivax: AMA-1 and MSP119 (57.0% and 90.5%,
      respectively). The cellular immune response to VIR antigens was evaluated by in
      vitro proliferative assays in mononuclear cells of the individuals recently
      exposed to P. vivax. No significant proliferative response to these antigens was
      observed when comparing malaria-exposed to non-exposed individuals. CONCLUSION:
      This study provides evidence that there is a low frequency of individuals
      responding to each VIR antigens in endemic areas of Brazil. This fact may explain
      the host susceptibility to new episodes of the disease.

PMID- 17026753
TI  - Ultrasound absorption and entropy production in biological tissue: a novel
      approach to anticancer therapy.
AB  - The entropy production of tumorous cells is higher than that of normal cells, and
      entropy flow is therefore directed from tumorous toward healthy cells. This
      results in information concerning the cancer propagating into the surrounding
      normal tissue. However, ultrasound absorption results in additional entropy
      production in tissues. The entropy mechanism possibly provides a basis for a
      novel approach to anticancer therapy through the use of ultrasound irradiation.
      METHODS: Through the calculation of ultrasound-induced entropy production and
      comparison of the theoretical results with the experimental data on ultrasound
      absorption in biological tissues, we have demonstrated that ultrasound absorption
      will increase the entropy in normal tissue more efficiently than in tumorous
      tissue due to the more acidic nature of the latter. Consequently, the direction
      of entropy flow between these two kinds of cells may be reversed on exposure to
      ultrasound. CONCLUSION: The higher entropy accumulation of normal cells during
      ultrasound irradiation may possibly lead to a change in the original direction of
      entropy flow and avoid the propagation of information on the cancer into the
      normal tissues. We suggest that low-intensity, low-frequency ultrasound
      irradiation may be an efficient tool for the therapy of solid tumors.

PMID- 17026754
TI  - Oxygen limitation modulates pH regulation of catabolism and hydrogenases,
      multidrug transporters, and envelope composition in Escherichia coli K-12.
AB  - BACKGROUND: In Escherichia coli, pH regulates genes for amino-acid and sugar
      catabolism, electron transport, oxidative stress, periplasmic and envelope
      proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the
      overall intersection of pH stress and oxygen limitation has not been
      investigated. RESULTS: The pH dependence of gene expression was analyzed in
      oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110
      was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and
      pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384
      genes and 610 intergenic regions. A core group of 251 genes showed pH responses
      similar to those in a previous study of cultures grown with aeration. The highly
      acid-induced gene yagU was shown to be required for extreme-acid resistance
      (survival at pH 2). Acid also up-regulated fimbriae (fimAC), periplasmic
      chaperones (hdeAB), cyclopropane fatty acid synthase (cfa), and the
      "constitutive" Na+/H+ antiporter (nhaB). Base up-regulated core genes for
      maltodextrin transport (lamB, mal), ATP synthase (atp), and DNA repair (recA,
      mutL). Other genes showed opposite pH responses with or without aeration, for
      example ETS components (cyo,nuo, sdh) and hydrogenases (hya, hyb, hyc, hyf, hyp).
      A hypF strain lacking all hydrogenase activity showed loss of extreme-acid
      resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis
      (rpl,rpm, rps). Acid up-regulated the catabolism of sugar derivatives whose
      fermentation minimized acid production (gnd, gnt, srl), and also a cluster of 13
      genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL), but
      down-regulated penicillin-binding proteins (dacACD, mreBC). Intergenic regions
      containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC).
      CONCLUSION: pH regulates a core set of genes independently of oxygen, including
      yagU, fimbriae, periplasmic chaperones, and nhaB. Under oxygen limitation,
      however, pH regulation is reversed for genes encoding electron transport
      components and hydrogenases. Extreme-acid resistance requires yagU and
      hydrogenase production. Ribosome synthesis is down-regulated at low pH under
      oxygen limitation, possibly due to the restricted energy yield of catabolism.
      Under oxygen limitation, pH regulates metabolism and transport so as to maximize
      alternative catabolic options while minimizing acidification or alkalinization of
      the cytoplasm.

PMID- 17026755
TI  - Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk
      factors, and outcome.
AB  - INTRODUCTION: The aim of this study was to determine incidence, risk factors, and
      impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas
      maltophilia. METHODS: This prospective observational case-control study, which
      was a part of a cohort study, was conducted in a 30-bed ICU during a three year
      period. All immunocompetent patients hospitalised >48 hours were eligible.
      Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were
      excluded. Patients without ICU-acquired S. maltophilia who developed an ICU
      acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal
      aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all
      patients at ICU admission and weekly. Univariate and multivariate analyses were
      performed to determine risk factors for ICU-acquired S. maltophilia and for ICU
      mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU
      acquired colonisation and/or infection and were all successfully matched with 76
      controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic
      treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p <
      0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated
      with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] =
      1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 +/- 16 versus
      7 +/- 11 days, p < 0.001), and duration of ICU stay (29 +/- 21 versus 15 +/- 17
      days, p < 0.001) were significantly higher in cases than in controls. In
      addition, ICU-acquired infection related to S. maltophilia was independently
      associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044).
      CONCLUSION: COPD and duration of antibiotic treatment are independent risk
      factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is
      associated with increased morbidity and mortality rates. ICU-acquired infection
      related to S. maltophilia is an independent risk factor for ICU mortality.

PMID- 17026756
TI  - Selection of housekeeping genes for gene expression studies in human
      reticulocytes using real-time PCR.
AB  - BACKGROUND: Control genes, which are often referred to as housekeeping genes, are
      frequently used to normalise mRNA levels between different samples. However, the
      expression level of these genes may vary among tissues or cells and may change
      under certain circumstances. Thus, the selection of housekeeping genes is
      critical for gene expression studies. To address this issue, 7 candidate
      housekeeping genes including several commonly used ones were investigated in
      isolated human reticulocytes. For this, a simple DeltaCt approach was employed by
      comparing relative expression of 'pairs of genes' within each sample. On this
      basis, stability of the candidate housekeeping genes was ranked according to
      repeatability of the gene expression differences among 31 samples. RESULTS:
      Initial screening of the expression pattern demonstrated that 1 of the 7 genes
      was expressed at very low levels in reticulocytes and was excluded from further
      analysis. The range of expression stability of the other 6 genes was (from most
      stable to least stable): GAPDH (glyceraldehyde 3-phosphate dehydrogenase), SDHA
      (succinate dehydrogenase), HPRT1 (hypoxanthine phosphoribosyl transferase 1),
      HBS1L (HBS1-like protein) and AHSP (alpha haemoglobin stabilising protein),
      followed by B2M (beta-2-microglobulin). CONCLUSION: Using this simple approach,
      GAPDH was found to be the most suitable housekeeping gene for expression studies
      in reticulocytes while the commonly used B2M should be avoided.

PMID- 17026757
TI  - Effects of 3-beta-diol, an androgen metabolite with intrinsic estrogen-like
      effects, in modulating the aquaporin-9 expression in the rat efferent ductules.
AB  - BACKGROUND: Fluid homeostasis is critical for normal function of the male
      reproductive tract and aquaporins (AQP) play an important role in maintenance of
      this water and ion balance. Several AQPs have been identified in the male, but
      their regulation is not fully comprehended. Hormonal regulation of AQPs appears
      to be dependent on the steroid in the reproductive tract region. AQP9 displays
      unique hormonal regulation in the efferent ductules and epididymis, as it is
      regulated by both estrogen and dihydrotestosterone (DHT) in the efferent
      ductules, but only by DHT in the initial segment epididymis. Recent data have
      shown that a metabolite of DHT, 5-alpha-androstane-3-beta-17-beta-diol (3-beta
      diol), once considered inactive, is also present in high concentrations in the
      male and indeed has biological activity. 3-beta-diol does not bind to the
      androgen receptor, but rather to estrogen receptors ER-alpha and ER-beta, with
      higher affinity for ER-beta. The existence of this estrogenic DHT metabolite has
      raised the possibility that estradiol may not be the only estrogen to play a
      major role in the male reproductive system. Considering that both ER-alpha and ER
      beta are highly expressed in efferent ductules, we hypothesized that the DHT
      regulation of AQP9 could be due to the 3-beta-diol metabolite. METHODS: To test
      this hypothesis, adult male rats were submitted to surgical castration followed
      by estradiol, DHT or 3-beta-diol replacement. Changes in AQP9 expression in the
      efferent ductules were investigated by using immunohistochemistry and Western
      blotting assay. RESULTS: Data show that, after castration, AQP9 expression was
      significantly reduced in the efferent ductules. 3-beta-diol injections restored
      AQP9 expression, similar to DHT and estradiol. The results were confirmed by
      Western blotting assay. CONCLUSION: This is the first evidence that 3-beta-diol
      has biological activity in the male reproductive tract and that this androgen
      metabolite has estrogen-like activity in the efferent ductules, whose major
      function is the reabsorption of luminal fluid.

PMID- 17026758
TI  - Inhibition of prefrontal protein synthesis following recall does not disrupt
      memory for trace fear conditioning.
AB  - BACKGROUND: The extent of similarity between consolidation and reconsolidation is
      not yet fully understood. One of the differences noted is that not every brain
      region involved in consolidation exhibits reconsolidation. In trace fear
      conditioning, the hippocampus and the medial prefrontal cortex (mPFC) are
      required for consolidation of long-term memory. We have previously demonstrated
      that trace fear memory is susceptible to infusion of the protein synthesis
      inhibitor anisomycin into the hippocampus following recall. In the present study,
      we examine whether protein synthesis inhibition in the mPFC following recall
      similarly results in the observation of reconsolidation of trace fear memory.
      RESULTS: Targeted intra-mPFC infusions of anisomycin or vehicle were performed
      immediately following recall of trace fear memory at 24 hours, or at 30 days,
      following training in a one-day or a two-day protocol. The present study
      demonstrates three key findings: 1) trace fear memory does not undergo protein
      synthesis dependent reconsolidation in the PFC, regardless of the intensity of
      the training, and 2) regardless of whether the memory is recent or remote, and 3)
      intra-mPFC inhibition of protein synthesis immediately following training
      impaired remote (30 days) memory. CONCLUSION: These results suggest that not all
      structures that participate in memory storage are involved in reconsolidation.
      Alternatively, certain types of memory-related information may reconsolidate,
      while other components of memory may not.

PMID- 17026760
TI  - Breast carcinoma and malignant melanoma metastasis within a single axillary lymph
      node.
AB  - A 58 year old lady presented with a right breast cancer and a prior history of
      malignant melanoma excised from the right chest wall eight years previously. An
      abnormal axillary lymph node resected contained features of both metastatic
      breast carcinoma and malignant melanoma. Following oncologic breast cancer
      management, the patient is well with no evidence of recurrence at three years.

PMID- 17026759
TI  - Breast cancer risk and drinking water contaminated by wastewater: a case control
      study.
AB  - BACKGROUND: Drinking water contaminated by wastewater is a potential source of
      exposure to mammary carcinogens and endocrine disrupting compounds from
      commercial products and excreted natural and pharmaceutical hormones. These
      contaminants are hypothesized to increase breast cancer risk. Cape Cod,
      Massachusetts, has a history of wastewater contamination in many, but not all, of
      its public water supplies; and the region has a history of higher breast cancer
      incidence that is unexplained by the population's age, in-migration, mammography
      use, or established breast cancer risk factors. We conducted a case-control study
      to investigate whether exposure to drinking water contaminated by wastewater
      increases the risk of breast cancer. METHODS: Participants were 824 Cape Cod
      women diagnosed with breast cancer in 1988-1995 and 745 controls who lived in
      homes served by public drinking water supplies and never lived in a home served
      by a Cape Cod private well. We assessed each woman's exposure yearly since 1972
      at each of her Cape Cod addresses, using nitrate nitrogen (nitrate-N) levels
      measured in public wells and pumping volumes for the wells. Nitrate-N is an
      established wastewater indicator in the region. As an alternative drinking water
      quality indicator, we calculated the fraction of recharge zones in residential,
      commercial, and pesticide land use areas. RESULTS: After controlling for
      established breast cancer risk factors, mammography, and length of residence on
      Cape Cod, results showed no consistent association between breast cancer and
      average annual nitrate-N (OR = 1.8; 95% CI 0.6-5.0 for > or = 1.2 vs. < .3 mg/L),
      the sum of annual nitrate-N concentrations (OR = 0.9; 95% CI 0.6-1.5 for > or =
      10 vs. 1 to < 10 mg/L), or the number of years exposed to nitrate-N over 1 mg/L
      (OR = 0.9; 95% CI 0.5-1.5 for > or = 8 vs. 0 years). Variation in exposure levels
      was limited, with 99% of women receiving some of their water from supplies with
      nitrate-N levels in excess of background. The total fraction of residential,
      commercial, and pesticide use land in recharge zones of public supply wells was
      associated with a small statistically unstable higher breast cancer incidence (OR
      = 1.4; 95% CI 0.8-2.4 for highest compared with lowest land use), but risk did
      not increase for increasing land use fractions. CONCLUSION: Results did not
      provide evidence of an association between breast cancer and drinking water
      contaminated by wastewater. The computer mapping methods used in this study to
      link routine measurements required by the Safe Drinking Water Act with interview
      data can enhance individual-level epidemiologic studies of multiple health
      outcomes, including diseases with substantial latency.

PMID- 17026761
TI  - Priority setting in developing countries health care institutions: the case of a
      Ugandan hospital.
AB  - BACKGROUND: Because the demand for health services outstrips the available
      resources, priority setting is one of the most difficult issues faced by health
      policy makers, particularly those in developing countries. However, there is lack
      of literature that describes and evaluates priority setting in these contexts.
      The objective of this paper is to describe priority setting in a teaching
      hospital in Uganda and evaluate the description against an ethical framework for
      fair priority setting processes--Accountability for Reasonableness. METHODS: A
      case study in a 1,500 bed national referral hospital receiving 1,320 out patients
      per day and an average budget of 13.5 million US dollars per year. We reviewed
      documents and carried out 70 in-depth interviews (14 health planners, 40 doctors,
      and 16 nurses working at the hospital). Interviews were recorded and transcribed.
      Data analysis employed the modified thematic approach to describe priority
      setting, and the description was evaluated using the four conditions of
      Accountability for Reasonableness: relevance, publicity, revisions and
      enforcement. RESULTS: Senior managers, guided by the hospital strategic plan make
      the hospital budget allocation decisions. Frontline practitioners expressed lack
      of knowledge of the process. RELEVANCE: Priority is given according to a cluster
      of factors including need, emergencies and patient volume. However, surgical
      departments and departments whose leaders "make a lot of noise" are also
      prioritized. Publicity: Decisions, but not reasons, are publicized through
      general meetings and circulars, but this information does not always reach the
      frontline practitioners. Publicity to the general public was through ad hoc radio
      programs and to patients who directly ask. Revisions: There were no formal
      mechanisms for challenging the reasoning. Enforcement: There were no mechanisms
      to ensure adherence to the four conditions of a fair process. CONCLUSION:
      Priority setting decisions at this hospital do not satisfy the conditions of
      fairness. To improve, the hospital should: (i) engage frontline practitioners,
      (ii) publicize the reasons for decisions both within the hospital and to the
      general public, and (iii) develop formal mechanisms for challenging the
      reasoning. In addition, capacity strengthening is required for senior managers
      who must accept responsibility for ensuring that the above three conditions are
      met.

PMID- 17026762
TI  - The difficult doctor? Characteristics of physicians who report frustration with
      patients: an analysis of survey data.
AB  - BACKGROUND: Literature on difficult doctor-patient relationships has focused on
      the "difficult patient." Our objective was to determine physician and practice
      characteristics associated with greater physician-reported frustration with
      patients. METHODS: We conducted a secondary analysis of the Physicians Worklife
      Survey, which surveyed a random national sample of physicians. Participants were
      1391 family medicine, general internal medicine, and medicine subspecialty
      physicians. The survey assessed physician and practice characteristics, including
      stress, depression and anxiety symptoms, practice setting, work hours, case-mix,
      and control over administrative and clinical practice. Physicians estimated the
      percentage of their patients who were "generally frustrating to deal with." We
      categorized physicians by quartile of reported frustrating patients and compared
      characteristics of physicians in the top quartile to those in the other three
      quartiles. We used logistic regression to model physician characteristics
      associated with greater frustration. RESULTS: In unadjusted analyses, physicians
      who reported high frustration with patients were younger (p < 0.001); worked more
      hours per week (p = 0.041); and had more symptoms of depression, stress, and
      anxiety (p < 0.004 for all). In the final model, factors independently associated
      with high frustration included age < 40 years, work hours > 55 per week, higher
      stress, practice in a medicine subspeciality, and greater number of patients with
      psychosocial problems or substance abuse. CONCLUSION: Personal and practice
      characteristics of physicians who report high frustration with patients differ
      from those of other physicians. Understanding factors contributing to physician
      frustration with patients may allow us to improve the quality of patient
      physician relationships.

PMID- 17026763
TI  - Validation of the Provincial Transfer Authorization Centre database: a
      comprehensive database containing records of all inter-facility patient transfers
      in the province of Ontario.
AB  - BACKGROUND: The Provincial Transfer Authorization Centre (PTAC) was established
      as a part of the emergency response in Ontario, Canada to the Severe Acute
      Respiratory Syndrome (SARS) outbreak in 2003. Prior to 2003, data relating to
      inter-facility patient transfers were not collected in a systematic manner. Then,
      in an emergency setting, a comprehensive database with a complex data collection
      process was established. For the first time in Ontario, population-based data for
      patient movement between healthcare facilities for a population of twelve million
      are available. The PTAC database stores all patient transfer data in a large
      database. There are few population-based patient transfer databases and the PTAC
      database is believed to be the largest example to house this novel dataset. A
      patient transfer database has also never been validated. This paper presents the
      validation of the PTAC database. METHODS: A random sample of 100 patient inter
      facility transfer records was compared to the corresponding institutional patient
      records from the sending healthcare facilities. Measures of agreement, including
      sensitivity, were calculated for the 12 common data variables. RESULTS: Of the
      100 randomly selected patient transfer records, 95 (95%) of the corresponding
      institutional patient records were located. Data variables in the categories
      patient demographics, facility identification and timing of transfer and reason
      and urgency of transfer had strong agreement levels. The 10 most commonly used
      data variables had accuracy rates that ranged from 85.3% to 100% and error rates
      ranging from 0 to 12.6%. These same variables had sensitivity values ranging from
      0.87 to 1.0. CONCLUSION: The very high level of agreement between institutional
      patient records and the PTAC data for fields compared in this study supports the
      validity of the PTAC database. For the first time, a population-based patient
      transfer database has been established. Although it was created during an
      emergency situation and data collection is dependent on front-line medical
      workers, the PTAC data has achieved a high level of validity, perhaps even higher
      than many purpose built databases created during non-emergency settings.

PMID- 17026764
TI  - In the absence of cancer registry data, is it sensible to assess incidence using
      hospital separation records?
AB  - BACKGROUND: Within the health literature, a major goal is to understand
      distribution of service utilisation by social location. Given equivalent access,
      differential incidence leads to an expectation of differential service
      utilisation. Cancer incidence is differentially distributed with respect to
      socioeconomic status. However, not all jurisdictions have incidence registries,
      and not all registries allow linkage with utilisation records. The British
      Columbia Linked Health Data resource allows such linkage. Consequently, we
      examine whether, in the absence of registry data, first hospitalisation can act
      as a proxy measure for incidence, and therefore as a measure of need for service.
      METHODS: Data are drawn from the British Columbia Linked Health Data resource,
      and represent 100% of Vancouver Island Health Authority cancer registry and
      hospital records, 1990-1999. Hospital separations (discharges) with principal
      diagnosis ICD-9 codes 140-208 are included, as are registry records with ICDO-2
      codes C00-C97. Non-melanoma skin cancer (173/C44) is excluded. Lung, colorectal,
      female breast, and prostate cancers are examined separately. We compare registry
      and hospital annual counts and age-sex distributions, and whether the same
      individuals are represented in both datasets. Sensitivity, specificity and
      predictive values are calculated, as is the kappa statistic for agreement. The
      registry is designated the gold standard. RESULTS: For all cancers combined,
      first hospitalisation counts consistently overestimate registry incidence counts.
      From 1995-1999, there is no significant difference between registry and hospital
      counts for lung and colorectal cancer (p = 0.42 and p = 0.56, respectively). Age
      sex distribution does not differ for colorectal cancer. Ten-year period
      sensitivity ranges from 73.0% for prostate cancer to 84.2% for colorectal cancer;
      ten-year positive predictive values range from 89.5% for female breast cancer to
      79.35% for prostate cancer. Kappa values are consistently high. CONCLUSION:
      Claims and registry databases overlap with an appreciable proportion of the same
      individuals. First hospital separation may be considered a proxy for incidence
      with reference to colorectal cancer since 1995. However, to examine equity across
      cancer health services utilisation, it is optimal to have access to both hospital
      and registry files.

PMID- 17026765
TI  - Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review.
AB  - Transcriptional silencing of tumor suppressor genes, associated with DNA
      methylation, is a common epigenetic event in hematologic malignancies. Although
      DNA hypermethylation of CpG islands is well described in acute leukemias and
      myelodysplastic syndromes, much less is known of the specific methylation changes
      that commonly occur in follicular B cell lymphomas. Earlier methylation studies
      of follicular lymphoma involved only cell lines; however there is a growing
      literature of methylation changes in primary human FL samples. Published studies
      of primary follicular lymphoma specimens have demonstrated that: androgen
      receptor, SHP1, and death-associated protein kinase genes are commonly
      methylated. By contrast, the cyclin dependent kinase inhibitors p15, p16, and p57
      are uncommon epigenetic events in follicular lymphoma. Methylation of cyclin
      dependent kinase inhibitors is more common in high grade lymphomas, and may be an
      important step in the progression and transformation of follicular lymphoma.
      Further methylation studies in follicular lymphoma should investigate the
      prognostic and therapeutic significance of these epigenetic changes and
      investigate methylation of other genes. Finally, reactivation of methylated tumor
      suppressor genes through the use of hypomethylating agents is a promising and
      novel approach to the treatment of indolent and transformed follicular lymphomas.

PMID- 17026766
TI  - Anticipating pulmonary complications after thoracotomy: the FLAM Score.
AB  - OBJECTIVE: Pulmonary complications after thoracotomy are the result of
      progressive changes in the respiratory status of the patient. A multifactorial
      score (FLAM score) was developed to identify postoperatively patients at higher
      risk for pulmonary complications at least 24 hours before the clinical diagnosis.
      METHODS: The FLAM score, created in 2002, is based on 7 parameters (dyspnea,
      chest X-ray, delivered oxygen, auscultation, cough, quality and quantity of
      bronchial secretions). To validate the FLAM score, we prospectively calculated
      scores during the first postoperative week in 300 consecutive patients submitted
      to posterolateral thoracotomy. RESULTS: During the study, 60 patients (20%)
      developed pulmonary complications during the postoperative period. The FLAM score
      progressively increased in complicated patients until the fourth postoperative
      day (mean 13.5 +/- 11.9). FLAM scores in patients with complications were
      significantly higher (p < 0.05) at least 24 hours before the clinical diagnosis
      of complication, compared to FLAM scores in uncomplicated patients. ROC curves
      analysis showed that the cut-off value of FLAM with the best sensitivity and
      specificity for pulmonary complications was 9 (area under the curve 0.97). Based
      on the highest FLAM scores recorded, 4 risk classes were identified with
      increasing incidence of pulmonary complications and mortality. CONCLUSION:
      Changes in FLAM score were evident at least 24 hours before the clinical
      diagnosis of pulmonary complications.FLAM score can be used to categorize
      patients according to risk of respiratory morbidity and mortality and could be a
      useful tool in the postoperative management of patients undergoing thoracotomy.

PMID- 17026767
TI  - Insights into the evolution of the ErbB receptor family and their ligands from
      sequence analysis.
AB  - BACKGROUND: In the time since we presented the first molecular evolutionary study
      of the ErbB family of receptors and the EGF family of ligands, there has been a
      dramatic increase in genomic sequences available. We have utilized this greatly
      expanded data set in this study of the ErbB family of receptors and their
      ligands. RESULTS: In our previous analysis we postulated that EGF family ligands
      could be characterized by the presence of a splice site in the coding region
      between the fourth and fifth cysteines of the EGF module and the placement of
      that module near the transmembrane domain. The recent identification of several
      new ligands for the ErbB receptors supports this characterization of an ErbB
      ligand; further, applying this characterization to available sequences suggests
      additional potential ligands for these receptors, the EGF modules from previously
      identified proteins: interphotoreceptor matrix proteoglycan-2, the alpha and beta
      subunit of meprin A, and mucins 3, 4, 12, and 17. The newly available sequences
      have caused some reorganizations of relationships among the ErbB ligand family,
      but they add support to the previous conclusion that three gene duplication
      events gave rise to the present family of four ErbB receptors among the
      tetrapods. CONCLUSION: This study provides strong support for the hypothesis that
      the presence of an easily identifiable sequence motif can distinguish EGF family
      ligands from other EGF-like modules and reveals several potential new EGF family
      ligands. It also raises interesting questions about the evolution of ErbB2 and
      ErbB3: Does ErbB2 in teleosts function differently from ErbB2 in tetrapods in
      terms of ligand binding and intramolecular tethering? When did ErbB3 lose kinase
      activity, and what is the functional significance of the divergence of its kinase
      domain among teleosts?

PMID- 17026768
TI  - Use of selected complementary and alternative medicine (CAM) treatments in
      veterans with cancer or chronic pain: a cross-sectional survey.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is emerging as an
      important form of care in the United States. We sought to measure the prevalence
      of selected CAM use among veterans attending oncology and chronic pain clinics
      and to describe the characteristics of CAM use in this population. METHODS: The
      self-administered, mail-in survey included questions on demographics, health
      beliefs, medical problems and 6 common CAM treatments (herbs, dietary
      supplements, chiropractic care, massage therapy, acupuncture and homeopathy) use.
      We used the chi-square test to examine bivariate associations between our
      predictor variables and CAM use. RESULTS: Seventy-two patients (27.3%) reported
      CAM use within the past 12 months. CAM use was associated with more education (p
      = 0.02), higher income (p = 0.006), non-VA insurance (p = 0.003), additional care
      outside the VA (p = 0.01) and the belief that lifestyle contributes to illness (p
      = 0.015). The diagnosis of chronic pain versus cancer was not associated with
      differential CAM use (p = 0.15). Seventy-six percent of CAM non-users reported
      that they would use it if offered at the VA. CONCLUSION: Use of 6 common CAM
      treatments among these veterans is lower than among the general population, but
      still substantial. A large majority of veterans reported interest in using CAM
      modalities if they were offered at the VA. A national assessment of veteran
      interest in CAM may assist VA leaders to respond to patients' needs.

PMID- 17026769
TI  - Medicinal plants used by traditional healers in Kancheepuram district of Tamil
      Nadu, India.
AB  - An ethnobotanical survey was undertaken to collect information from traditional
      healers on the use of medicinal plants in Kancheepuram district of Tamil Nadu
      during October 2003 to April 2004. The indigenous knowledge of local traditional
      healers and the native plants used for medicinal purposes were collected through
      questionnaire and personal interviews during field trips.The investigation
      revealed that, the traditional healers used 85 species of plants distributed in
      76 genera belonging to 41 families to treat various diseases. The documented
      medicinal plants were mostly used to cure skin diseases, poison bites,
      stomachache and nervous disorders. In this study the most dominant family was
      Euphorbiaceae and leaves were most frequently used for the treatment of
      diseases.This study showed that many people in the studied parts of Kancheepuram
      district still continue to depend on medicinal plants at least for the treatment
      of primary healthcare. The traditional healers are dwindling in number and there
      is a grave danger of traditional knowledge disappearing soon since the younger
      generation is not interested to carry on this tradition.

PMID- 17026770
TI  - Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease.
AB  - Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to
      play a role in the pathogenesis of many inflammatory diseases. Although this
      enzyme has also been implicated in the pathogenesis of neurodegenerative
      diseases, there has not been a direct demonstration of its expression in diseased
      human brain. In this study, we show that sPLA2-IIA mRNA is up-regulated in
      Alzheimer's disease (AD) brains as compared to non-demented elderly brains (ND).
      We also report a higher percentage of sPLA2-IIA-immunoreactive astrocytes present
      in AD hippocampus and inferior temporal gyrus (ITG). In ITG, the majority of
      sPLA2-IIA-positive astrocytes were associated with amyloid beta (Abeta)
      containing plaques. Studies with human astrocytes in culture demonstrated the
      ability of oligomeric Abeta1-42 and interleukin-1beta (IL-1beta) to induce sPLA2
      IIA mRNA expression, indicating that this gene is among those induced by
      inflammatory cytokines. Since exogenous sPLA2-IIA has been shown to cause
      neuronal injury, understanding the mechanism(s) and physiological consequences of
      sPLA2-IIA upregulation in AD brain may facilitate the development of novel
      therapeutic strategies to inhibit the inflammatory responses and to retard the
      progression of the disease.

PMID- 17026772
TI  - Malignant potential of intrahepatic biliary papillomatosis: a case report and
      review of the literature.
AB  - BACKGROUND: Biliary papillomatosis (BP) is a rare disease entity with a strong
      malignant potential. It is characterized by multiple papillary adenomas involving
      both the intrahepatic and extrahepatic biliary tree. BP was considered in the
      past to be a disease with low malignant potential. However, a current review of
      the English literature revealed a high rate of malignant occurrence of
      approximately 41% and histological analysis along with the expression pattern of
      mucin core proteins (MUC) and mucin carbohydrate antigens suggests that BP is a
      borderline or low grade malignant neoplasm with a high malignant potential. CASE
      PRESENTATION: A 68 year-old male patient was referred to our hospital due to the
      presence of sudden right upper quadrant abdominal pain, nausea and dark urine.
      Imaging workup demonstrated dilatation of the left hepatic duct without the
      presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were
      carried out and histological analysis revealed a moderately to poorly
      differentiated carcinoma of the left hepatic duct in the background of biliary
      papillomatosis. Postoperative course was uneventful. Unfortunately, two years
      after initial diagnosis the patient rapidly deteriorated and died from multiple
      pulmonary secondary deposits. CONCLUSION: BP should not be considered to be a
      benign disease. The clinical behavior, the high recurrence rate and the even
      higher malignant transformation occurrence, as well as the presence of
      carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn
      antigens) strongly support that BP is a low-grade neoplasm with high malignant
      potential.

PMID- 17026771
TI  - Finasteride induced depression: a prospective study.
AB  - BACKGROUND: Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme,
      and is used for treatment of benign prostatic hyperplasia and androgenetic
      alopecia. Animal studies have shown that finasteride might induce behavioral
      changes. Additionally, some cases of finasteride-induced depression have been
      reported in humans. The purpose of this study was to examine whether depressive
      symptoms or anxiety might be induced by finasteride administration. METHODS: One
      hundred and twenty eight men with androgenetic alopecia, who were prescribed
      finasteride (1 mg/day) were enrolled in this study. Information on depressed mood
      and anxiety was obtained by Beck Depression Inventory (BDI), and Hospital Anxiety
      and Depression Scale (HADS). Participants completed BDI and HADS questionnaires
      before beginning the treatment and also two months after it. RESULTS: Mean age of
      the subjects was 25.8(+/- 4.4) years. At baseline, mean BDI and HADS depression
      scores were 12.11(+/- 7.50) and 4.04(+/- 2.51), respectively. Finasteride
      treatment increased both BDI (p < 0.001) and HADS depression scores significantly
      (p = 0.005). HADS anxiety scores were increased, but the difference was not
      significant (p = 0.061). CONCLUSION: This preliminary study suggests that
      finasteride might induce depressive symptoms; therefore this medication should be
      prescribed cautiously for patients with high risk of depression. It seems that
      further studies would be necessary to determine behavioral effects of this
      medication in higher doses and in more susceptible patients.

PMID- 17026773
TI  - Methylene blue for malaria in Africa: results from a dose-finding study in
      combination with chloroquine.
AB  - The development of safe, effective and affordable drug combinations against
      malaria in Africa is a public health priority. Methylene blue (MB) has a similar
      mode of action as chloroquine (CQ) and has moreover been shown to selectively
      inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled
      dose-finding study on the combination MB-CQ was performed in 435 young children
      with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50%
      clinical failure rate in this area in 2003). Three serious adverse events (SAE)
      occurred of which one was probably attributable to the study medication. In the
      per protocol safety analysis, there were no dose specific effects. The overall
      clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%,
      14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have
      efficacy against malaria, but the combination of CQ-MB is clearly not effective
      in the treatment of malaria in Africa.

PMID- 17026774
TI  - Abdominal wall implantation of hepatocellular carcinoma.
AB  - BACKGROUND: Percutaneous fine needle aspiration cytology (FNAC) became a popular
      method for diagnosis of hepatic masses. Abdominal wall implantation from FNAC is
      rare. CASE PRESENTATION: We report a female patient who presented with a right
      upper abdominal wall mass 3 years following a fine needle aspiration cytology
      (FNAC) and resection of a solitary hepatocellular carcinoma (HCC) from the liver.
      The mass proved to be a metastatic HCC; it was locally resected with safety
      margins. To date (20 months later) she remains well with no recurrence.
      CONCLUSION: Implantation of tumor cells after FNAC for HCC is rare, but can
      happen. The availability of dynamic imaging of the liver should reduce the need
      for this technique in the diagnostic workup of patients suspected of having HCC.

PMID- 17026775
TI  - STAR: predicting recombination sites from amino acid sequence.
AB  - BACKGROUND: Designing novel proteins with site-directed recombination has
      enormous prospects. By locating effective recombination sites for swapping
      sequence parts, the probability that hybrid sequences have the desired properties
      is increased dramatically. The prohibitive requirements for applying current
      tools led us to investigate machine learning to assist in finding useful
      recombination sites from amino acid sequence alone. RESULTS: We present STAR,
      Site Targeted Amino acid Recombination predictor, which produces a score
      indicating the structural disruption caused by recombination, for each position
      in an amino acid sequence. Example predictions contrasted with those of
      alternative tools, illustrate STAR'S utility to assist in determining useful
      recombination sites. Overall, the correlation coefficient between the output of
      the experimentally validated protein design algorithm SCHEMA and the prediction
      of STAR is very high (0.89). CONCLUSION: STAR allows the user to explore useful
      recombination sites in amino acid sequences with unknown structure and unknown
      evolutionary origin. The predictor service is available from
      http://pprowler.itee.uq.edu.au/star.

PMID- 17026777
TI  - Development of a new set of reference genes for normalization of real-time RT-PCR
      data of porcine backfat and longissimus dorsi muscle, and evaluation with
      PPARGC1A.
AB  - BACKGROUND: An essential part of using real-time RT-PCR is that expression
      results have to be normalized before any conclusions can be drawn. This can be
      done by using one or multiple, validated reference genes, depending on the
      desired accuracy of the results. In the pig however, very little information is
      available on the expression stability of reference genes. The aim of this study
      was therefore to develop a new set of reference genes which can be used for
      normalization of mRNA expression data of genes expressed in porcine backfat and
      longissimus dorsi muscle, both representing an economically important part of a
      pig's carcass. Because of its multiple functions in fat metabolism and muscle
      fibre type composition, peroxisome proliferative activated receptor gamma
      coactivator 1alpha (PPARGC1A) is a very interesting candidate gene for meat
      quality, and was an ideal gene to evaluate our developed set of reference genes
      for normalization of mRNA expression data of both tissue types. RESULTS: The mRNA
      expression stability of 10 reference genes was determined. The expression of
      RPL13A and SDHA appeared to be highly unstable. After normalization to the
      geometric mean of the three most stably expressed reference genes (ACTB, TBP and
      TOP2B), the results not only showed that the mRNA expression of PPARGC1A was
      significantly higher in each of the longissimus dorsi muscle samples than in
      backfat (P < 0.05), but also that the expression was significantly higher in the
      most cranial of the three muscle samples (P < 0.05). CONCLUSION: This study
      provides a new set of reference genes (ACTB, TBP and TOP2B) suitable for
      normalization of real-time RT-PCR data of backfat and longissimus dorsi muscle in
      the pig. The obtained PPARGC1A expression results, after application of this set
      of reference genes, are a first step in unravelling the PPARGC1A expression
      pattern in the pig and provide a basis for possible selection towards improved
      meat quality while maintaining a lean carcass.

PMID- 17026778
TI  - An estimate of the prevalence of dementia among residents of long-term care
      geriatric institutions in the Jerusalem area.
AB  - BACKGROUND: To determine the prevalence of dementia among the residents of
      geriatric institutions in the greater Jerusalem area. METHODS: A population
      based, cross-sectional survey of a representative sample, weighted according to
      the level of care, of 11 of the 88 long-term care (LTC) wards in 34 LTC
      institutions providing care for the elderly residents in the greater Jerusalem
      area in 1999. A single physician interviewed 311 residents. The presence of
      dementia was determined from medical records and by performance on the Modified
      Mini-mental State Examination (3MS) instrument (with a score less than 78/100
      indicating significant cognitive impairment or suspected dementia), and
      professional care providers were interviewed for their opinion regarding the
      presence of dementia in each subject. RESULTS: The mean age of the patients was
      83.9 years and 75% were women. Overall, 180 residents, representing 49.9% of the
      weighted sample in Jerusalem LTC facilities, were determined to have dementia
      according to medical records, ranging from 22.9% in independent and frail care
      units to 97.7% in skilled nursing care wards. However, based on their performance
      on the 3MS, the prevalence of cognitive impairment with suspected dementia among
      the subjects was substantially greater, with the staff being unaware of this
      diagnosis in about one-quarter of the subjects. CONCLUSIONS: There is a high
      prevalence of dementia in geriatric institutions in the Jerusalem area,
      particularly in those providing greater care. Moreover, significant cognitive
      impairment is probably under-reported in the medical records.

PMID- 17026776
TI  - Fatigue states after cancer treatment occur both in association with, and
      independent of, mood disorder: a longitudinal study.
AB  - BACKGROUND: Persistent fatigue is recognised as one of the most common, ongoing
      symptoms reported by patients following cancer treatment and may have profound
      effects on the quality of life. However, recent cross-sectional studies also
      highlight the close relationship between cancer related fatigue (CRF) and
      diagnoses of depression or anxiety disorder. There is currently limited
      information about the relationships between these conditions over time. We sought
      to examine the longitudinal relationships between fatigue and mood disorder in
      women treated with adjuvant therapy for early stage breast cancer. METHODS: Women
      who had recently completed adjuvant therapy for Stage I or II breast cancer (n =
      212) were sent a questionnaire with established case thresholds for clinically
      significant fatigue and psychological disorder, as well as a questionnaire
      assessing disability. Potentially relevant variables linked to fatigue states,
      including age, treatment modality, menopausal status, and hematological indices
      were recorded. The illness outcomes were assessed over 48 months of follow-up.
      RESULTS: The 176 women who responded to the questionnaire (84%) had a mean age of
      55 (range 24-83) years and had completed adjuvant treatment on average 10 (range
      4.7-16.3) months previously. Radiotherapy had been administered, either alone
      (50% of women) or in combination with chemotherapy (36%). Responses from 87 women
      (48%) indicated a significant fatigue state (termed here post-cancer fatigue;
      PCF), and from 59 women (33%) responses indicated significant psychological
      distress. Thirty-four women (19%) were cases of fatigue alone (i.e. unaccompanied
      by psychological disorder), whereas 52 (30%) were cases of both disorders.
      Multivariate analysis did not reveal any association between demographic,
      clinical or laboratory variables, and caseness for PCF. Self-reported functional
      disability was significantly associated with fatigue. Follow-up at 24, 36 and 48
      months revealed high rates of ongoing PCF in conjunction with psychological
      distress, despite falling rates of psychological distress alone and fatigue
      alone. CONCLUSION: Post-cancer fatigue was prevalent and sustained on follow-up.
      Concurrent psychological disorder was evident in the majority, but not all, cases
      of PCF and tended to be sustained over time. Further prospective cohort studies
      to define the longitudinal co-morbid relationships between fatigue, mood
      disorder, and ongoing disability after cancer treatment are indicated.

PMID- 17026779
TI  - Visual hallucinations and amnesia associated with zolpidem triggered by
      fluvoxamine: a possible interaction.

PMID- 17026780
TI  - A practice audit of maintenance electroconvulsive therapy in the elderly.

PMID- 17026781
TI  - Implications of daily, monthly and seasonal variation of new referrals for
      working patterns of a community mental health team.

PMID- 17026782
TI  - Catechol-o-methyltransferase gene polymorphism in dementia with Lewy bodies
      related psychosis: evidence for a genetic predisposition.

PMID- 17026783
TI  - Towards education-fair dementia screening.

PMID- 17026785
TI  - The role of a drug holiday: even patients with cancer need a vacation.

PMID- 17026784
TI  - Noradrenaline-induced smooth muscle relaxation in the specific region of canine
      facial vein: implications for facial and cranial circulation.
AB  - This study was performed to investigate the heterogeneity of physiological and
      pharmacological properties in segments of the facial veins with special reference
      to selective brain cooling. Canine facial veins were isolated and the isometric
      tension of each segment was measured using the organ bath technique. Vessels in
      the segments of the facial veins that run opposite to the buccal cavity
      automatically produced myogenic tone and tended to show spontaneous contractions,
      but vessels in other segments did not. When no contractile agent was used for
      precontraction, noradrenaline and adrenaline produced dose-dependent relaxations
      in the former venous segments, but contractions in the latter ones. A Schild plot
      analysis for metoprolol against denopamine and for ICI118,551 against salbutamol
      showed that the venous segments running opposite the buccal cavity contained both
      beta(1)- and beta(2)-adrenoceptors, but the other venous segments contained only
      beta(2)-adrenoceptors. Electrical field stimulation-induced tetrodotoxin
      sensitive relaxations in the former venous segments were diminished by
      pretreatment with metoprolol, but not with ICI118,551, indicating that the
      electrical stimulation-induced relaxation may be related to the activation of
      beta(1)-adrenoceptors in the venous smooth muscles. In conclusion, the
      heterogeneity of the functional properties, especially in the distribution of
      beta-adrenoceptors, in different segments of canine facial veins was observed in
      the present study, and autoregulatory mechanisms, humoral mechanisms, and neural
      mechanisms were suggested to affect cranial venous drainage.

PMID- 17026786
TI  - Highlights from: 42nd Annual Meeting of the American Society of Clinical
      Oncology.

PMID- 17026787
TI  - Safety of bevacizumab with fluoropyrimidine-based regimens for first-line
      treatment of metastatic colorectal cancer.

PMID- 17026788
TI  - Do all patients with metastatic colorectal cancer need chemotherapy until disease
      progression?
AB  - The question of continuous versus intermittent chemotherapy for patients with
      metastatic colorectal cancer has been an ongoing issue of debate for determining
      the optimum duration of treatment. The results from 2 major trails addressing
      this issue were recently presented at the 2006 Annual Meeting of the American
      Society of Clinical Oncology. The OPTIMOX2 trial evaluated the efficacy and
      safety of oxaliplatin reintroduction after a complete chemotherapy-free interval
      or maintenance therapy in patients with previously untreated disease. The GISCAD
      (Italian Group for the Study of Digestive Tract Cancer) study investigated the
      utility of intermittent versus continuous irinotecan-based chemotherapy. Both
      studies demonstrated that chemotherapy can be administered intermittently without
      affecting the overall efficacy of treatment.

PMID- 17026789
TI  - Liver resection for metastatic colorectal cancer in the age of neoadjuvant
      chemotherapy and bevacizumab.
AB  - Hepatic metastases from colorectal carcinoma (CRC) were once thought to portend a
      uniformly grim outcome; however, improvements in chemotherapeutic and surgical
      approaches have led to significant advances as well as new clinical challenges.
      Some 60% of the 150,000 patients diagnosed with CRC each year in the United
      States will develop hepatic metastases. Only a fraction of these metastases are
      resectable at the time of presentation, but an increasing number of patients are
      able to undergo resection after neoadjuvant chemotherapy. Additionally, recent
      trials have demonstrated the efficacy of using chemotherapy with bevacizumab as
      first-line therapy for metastatic CRC, but how this treatment will affect
      surgical resection is unknown. Herein, we review the recent literature regarding
      neoadjuvant chemotherapy for hepatic metastases from CRC, discuss key aspects of
      the basic science of hepatic regeneration with regard to angiogenic mediators,
      and outline the key problems to be solved so that a rational strategy can be
      developed to treat patients with hepatic colorectal metastases in the age of
      neoadjuvant chemotherapy and antiangiogenic drugs.

PMID- 17026791
TI  - Epidermal growth factor receptor and epidermal growth factor receptor variant III
      gene expression in metastatic colorectal cancer.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) variant type III (variously
      called EGFRvIII, de2-7 EGFR, or triangle upEGFR) has an in-frame deletion of the
      extracellular domain and is found in numerous types of human tumors. Because
      EGFRvIII has been reported to be tumor specific and has oncogenic potential, it
      is being investigated as a potential therapeutic target, but to our knowledge,
      there is only 1 previous report about EGFRvIII by immunohistochemistry in
      colorectal cancer. Our aim was to indicate the frequency of gene expressions of
      EGFRvIII and EGFR in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:
      Forty-five patients with mCRC who received the chemotherapy for metastatic
      disease were analyzed for the EGFRvIII variant. Paraffin-embedded tumor tissues
      were dissected using laser-captured microdissection and analyzed for the EGFR and
      EGFRvIII messenger RNA expression using a quantitative real-time reverse
      transcriptase polymerase chain reaction method. Gene expression values (relative
      messenger RNA levels) are expressed as ratios (differences from the cycle
      threshold values) between the target gene and internal reference gene (beta
      actin). Twenty-five women and 20 men with a median age of 55 years (range, 25-76
      years) were included in this study. RESULTS: We did not find any expression of
      EGFRvIII in these 45 patients except for control cell lines as U87.EGFRvIII.
      However, EGFR gene expression was found in 43 of 45 (95.6%) with a range of 0.38
      2.83. CONCLUSION: Our results demonstrate that the expression of EGFRvIII is
      rare, but most colon cancer demonstrates EGFR gene expression. We conclude that
      EGFRvIII does not play an important role in mCRC.

PMID- 17026790
TI  - Phase I study of gefitinib plus FOLFIRI in previously untreated patients with
      metastatic colorectal cancer.
AB  - BACKGROUND: In this study, the maximum tolerated dose and toxicity profile of
      FOLFIRI (infusional fluorouracil [5-FU]/leucovorin/irinotecan) plus gefitinib (an
      oral inhibitor of the epidermal growth factor receptor) were evaluated as first
      line therapy in patients with metastatic colorectal cancer. PATIENTS AND METHODS:
      Sixteen patients participated in this study. Oral gefitinib was administered at
      250 mg or 500 mg daily in 2 dose-escalation cohorts. FOLFIRI was administered
      without dose escalation on a 14-day cycle with treatment on day 1 with irinotecan
      180 mg/m2, leucovorin 200 mg/m2, and 5-FU 400 mg/m2 bolus, followed by 5-FU 2400
      mg/m2 continuous infusion over 46 hours. RESULTS: The maximum tolerated dose of
      gefitinib was 250 mg, with diarrhea and neutropenia noted as the principal dose
      limiting toxicities. Dose reductions in 5-FU and irinotecan were required in 4
      patients because of diarrhea and 1 patient because of neutropenia. A partial
      response was observed in 25% of patients, and 56% had stable disease for > 12
      weeks, corresponding to a disease control rate of 81%. CONCLUSION: These findings
      suggest that gefitinib can be safely combined with FOLFIRI as first-line
      treatment of metastatic CRC and support the safety of further investigations of
      EGFR tyrosine kinase inhibitors with multiagent chemotherapy in this patient
      population.

PMID- 17026792
TI  - Hand-foot syndrome variant in a dihydropyrimidine dehydrogenase-deficient patient
      treated with capecitabine.
AB  - We present a case with dihydropyrimidine dehydrogenase (DPD) deficiency that
      manifested a variant of hand-foot syndrome (HFS). A 52-year-old man received
      capecitabine for adjuvant treatment of rectal cancer. On the ninth day of the
      first cycle, he presented to the clinic with a rash on the dorsum of both hands
      accompanied by symptoms of pain, erythema, swelling, and desquamation consistent
      with grade 3 HFS. The palms of his hands and soles of his feet were only tender
      with no apparent rash or discoloration. Dihydropyrimidine dehydrogenase activity
      was evaluated by radio assay using peripheral blood mononuclear cells.
      Dihydropyrimidine dehydrogenase activity was below normal: 0.12 nmol/minute/mg
      protein. Capecitabine was not resumed, and the rash resolved in 3 weeks with the
      use of pyridoxine and Udderly Smooth balm. Interestingly, HFS is rarely seen with
      5-fluorouracil regimens containing selective DPD-inhibitors. This patient with
      DPD deficiency manifested a variant of HFS. The pharmacologic basis for the
      development of HFS in DPD-deficient patients warrants further investigation.
      Dihydropyrimidine dehydrogenase deficiency, if undiagnosed, can lead to death. In
      addition to severe to life-threatening toxicities akin to 5-fluorouracil,
      capecitabine can lead to unusual variants of common toxicities, including HFS, in
      DPD-deficient patients.

PMID- 17026793
TI  - Ocular toxicity related to cetuximab monotherapy in patients with colorectal
      cancer.
AB  - Cetuximab is a monoclonal antibody that specifically blocks the epidermal growth
      factor receptor pathway. Cetuximab is now a standard drug to treat refractory
      advanced colorectal cancer. The most common side effect is a rash, seen in most
      patients. Ocular toxicity is uncommon. We report 2 cases of ocular toxicity
      characterized by blepharitis and conjunctivitis related to cetuximab
      administration. Strategies for management are discussed.

PMID- 17026794
TI  - Streptococcus suis endocarditis and colon carcinoma: a case report.
AB  - Streptococcus bovis has classically been associated with colorectal carcinomas in
      literature. Curiously enough, no other Streptococcus species have hitherto been
      associated with such a malignancy or any other tumors. This report presents a
      case of early-stage colorectal carcinoma diagnosed in a patient with infection
      with the related Streptococcus species S suis. A discussion of possible
      pathogenetic implications follows.

PMID- 17026796
TI  - Assessing progress against prostate cancer.

PMID- 17026795
TI  - Phase III multicenter randomized clinical trial to evaluate the safety and
      efficacy of CoFactor/5-fluorouracil/bevacizumab versus leucovorin/5
      fluorouracil/bevacizumab as initial treatment for metastatic colorectal
      carcinoma.

PMID- 17026797
TI  - Highlights from: the third International Congress on Kidney and Bladder Cancer.
      Orlando, FL; August 3-6, 2006.

PMID- 17026798
TI  - Current data with mammalian target of rapamycin inhibitors in advanced-stage
      renal cell carcinoma.
AB  - Mammalian target of rapamycin (mTOR) is the key regulator of cell growth and
      proliferation. Alterations in the mTOR signaling pathway can lead to neoplastic
      transformation and progression. The inhibition of mTOR blocks the progression of
      the cell cycle from G1 to S phase, leading to cell growth arrest and apoptosis.
      Thus, mTOR is a promising target for the treatment of human malignancies.
      Rapamycin and its analogues, including temsirolimus, everolimus, and AP23573,
      block the mTOR signaling pathway and induce a cellular state akin to starvation,
      with significant antitumor activity in a variety of malignancies, including renal
      cell carcinoma (RCC). Current data from ongoing clinical trials suggest that mTOR
      targeted therapy with rapamycin derivatives is well tolerated with significant
      clinical activity in patients with advanced-stage RCC. Specifically, temsirolimus
      as monotherapy has demonstrated improved progression-free and overall survival in
      patients with poor-risk advanced-stage RCC. Everolimus has also demonstrated
      promising antitumor activity in patients with metastatic RCC. However, optimal
      dose, treatment schedule, selection of patients, and appropriate combination
      strategies with other novel agents need to be defined for mTOR-targeted therapies
      in the treatment of advanced-stage RCC.

PMID- 17026799
TI  - Interleukin-2 therapy of metastatic renal cell carcinoma: update of phase III
      trials.
AB  - High-dose bolus interleukin-2 (IL-2) was granted Food and Drug Administration
      approval for the treatment of metastatic renal cell carcinoma based on its
      ability to produce durable responses in a small number of patients. Results from
      randomized phase III trials suggest that regimens involving lower doses of IL-2
      alone or in combination with interferon produce fewer tumor regressions of
      decreased overall quality. Because of the toxicity and limited efficacy of this
      treatment, recent studies have focused on identifying predictors of response (or
      resistance) to IL-2 therapy. This year, investigators will launch a clinical
      trial designed to prospectively determine whether patients who are more likely to
      respond to high-dose IL-2 can be identified before therapy is initiated.

PMID- 17026800
TI  - Adjuvant therapy of renal cell carcinoma.
AB  - Metastatic renal cell carcinoma (RCC) has a highly variable natural history and
      carries a dismal prognosis. Unlike many other tumors, RCC is generally
      unresponsive to cytotoxic, hormonal, and radiation adjuvant therapies after
      cytoreductive surgery. Different modalities of treatment have been tried and
      tested with modest success. Until recently, only immunotherapies such as
      interleukin-2 and interferon-alpha have been shown to provide a response, albeit
      in a minority of patients and often with severe treatment-associated toxicities.
      Other adjuvant therapies, such as active specific immunotherapy with Bacillus
      Calmette-Guerin and autologous renal tumor cell vaccines, have not provided
      alternative solutions. Recent approaches include heat-shock protein peptide
      complex 96 vaccine and cG250 monoclonal antibody therapy. Novel targeted
      therapies have been developed using our knowledge of the molecular genetics that
      belie RCC. This culminated in sorafenib and sunitinib, the first Food and Drug
      Administration-approved drugs for RCC in more than a decade in the United States.
      The future will see further trials being carried out in the development of
      targeted therapies with emphasis placed on patient selection. Staging systems
      will need to be updated to integrate molecular biomarkers, which could
      potentially act not just as diagnostic and prognostic predictors, but also as
      tools for appropriate patient selection for treatment. In the future, this could
      potentially lead us to our ultimate goal of personalized medicine.

PMID- 17026801
TI  - A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone
      refractory prostate cancer.
AB  - PURPOSE: The objective of this phase II study was to determine the response rate
      in patients with hormone-refractory prostate cancer given
      paclitaxel/estramustine/carboplatin for weeks 1, 2, and 3 of a 4-week cycle.
      PATIENTS AND METHODS: Eighty-four patients were registered into the trial.
      Paclitaxel 80 mg/m2 and carboplatin area under the curve of 2 were administered
      intravenously on days 2, 9, and 16, and oral estramustine 280 mg 3 times daily
      was given on days 1-3, 8-10, and 15-17 for 6 cycles. Eastern Cooperative Oncology
      Group performance status 0, 1, and 2 was 46%, 41%, and 13%, respectively, and
      median age was 70 years (range, 53-82 years), with 58 patients (69%) aged > 65
      years. The majority of patients (83%) were white. Fifteen patients (18%) had
      received previous chemotherapy, 61 patients (73%) had undergone previous surgery,
      and 51 patients (61%) had received previous external-beam radiation therapy.
      RESULTS: Intent-to-treat analysis revealed a > or = 50% prostate-specific antigen
      decrease rate of 61%. Median survival was 15.3 months. The most frequent grade >
      or = 3 toxicities included fatigue (11%), nausea (10%), neutropenia (9%), anemia
      (6%), and vomiting (6%). CONCLUSION: Paclitaxel/estramustine/carboplatin
      administered in a weekly regimen is highly effective in the treatment of hormone
      refractory prostate cancer and can be administered with reasonable safety in an
      outpatient setting.

PMID- 17026802
TI  - Intermittent hormone therapy in nonmetastatic prostate cancer.
AB  - PURPOSE: The object of this study was to evaluate the duration of response to
      intermittent androgen deprivation (IAD) in patients with nonmetastatic recurrent
      or localized prostate cancer. PATIENTS AND METHODS: One hundred ten patients
      received IAD from February 1992 to February 2005. One hundred three patients were
      treated after failure of primary radiation therapy and/or prostatectomy, with the
      remaining 7 patients treated primarily with IAD. The median duration of treatment
      cycle was 6 months. Patients were considered resistant to hormone therapy if the
      prostate-specific antigen (PSA) level increased, with castrate levels of
      testosterone. At the time of initial diagnosis, the median Gleason score was 7
      (range, 4-9), and tumor stages were as follows: T1/T2 (n = 73), T3 and T4 N1 (n =
      34), and other (n = 3). The median PSA at the initiation of IAD was 8.25 ng/mL.
      RESULTS: The median follow-up after beginning IAD was 45.5 months. Patients
      received a median of 2 cycles (range, 1-9 cycles). Ninety-four of 110 patients
      (85.5%) remained responsive to IAD. Sixteen patients (14.5%) progressed to become
      refractory to primary hormone treatment. Patients with a higher tumor stage (T3
      and T4) were significantly more likely to develop resistance. The median time to
      become refractory to hormone therapy was 47.9 months (range, 9.4-93.4 months).
      Five patients were put on secondary continuous hormone treatment, and 3 of them
      developed resistance at a median of 9 months. One patient was put on a secondary
      IAD and was still responding at the last follow-up. CONCLUSION: With 85.5% of the
      original patient population still responding to the primary hormone therapy at
      45.5 months of follow-up, IAD appears to be a viable option for patients with
      biochemical failure after local radiation therapy. A pattern of shortening time
      between cycles and an increasing nadir PSA level with each successive cycle is
      consistent with the gradual development of hormone resistance.

PMID- 17026803
TI  - Thalidomide/estramustine/paclitaxel in metastatic androgen-independent prostate
      cancer.
AB  - BACKGROUND: This is a phase I/II trial of thalidomide with estramustine and
      paclitaxel in men with androgen-independent prostate cancer (AIPC) who underwent
      previous chemotherapy. PATIENTS AND METHODS: Men with progressive AIPC were
      treated with oral thalidomide (200 mg, 400 mg, or 600 mg daily), intravenous
      paclitaxel (100 mg/m2 over 3 hours on days 3 and 10), and oral estramustine (140
      mg 3 times daily on days 1-5 and days 8-12) every 21 days. RESULTS: Phase I:
      first cycle dose-limiting toxicity occurred in 0 of 3 patients at 200 mg
      thalidomide daily, 0 of 3 at 400 mg daily, and 1 of 3 at 600 mg daily (the
      designated maximum tolerated dose). Phase II: twenty-nine of 38 evaluable
      patients (76%; 95% confidence interval, 67%-87%) experienced a 50% decrease in
      prostate-specific antigen level. Five of 18 patients (28%) with measurable
      disease exhibited an objective response. Nine of 14 patients (64%) with disease
      refractory to previous taxane therapy had 50% decreases in prostate-specific
      antigen level. Grade 3/4 adverse events included neutropenia (9 of 39 [23%]),
      fatigue (9 of 39 [23%]), dyspnea (8 of 39 [21%]), and thromboembolic events (7 of
      39 [18%]). Cumulative dose-limiting toxicity rates were minimal (13%) with
      thalidomide at 200 mg daily. CONCLUSION: The profile of activity of
      thalidomide/paclitaxel/estramustine in taxane-refractory AIPC warrants further
      investigation.

PMID- 17026804
TI  - Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in
      patients with locally advanced bladder cancer.
AB  - BACKGROUND: Despite the general acceptance of gemcitabine/cisplatin in metastatic
      bladder cancer, its role and tolerability in the adjuvant setting, in which renal
      insufficiency is common, is unclear. PATIENTS AND METHODS: A total of 39 patients
      with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2)
      were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical
      cystectomy. All toxicities were evaluated by the National Cancer Institute Common
      Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53,
      and p16. RESULTS: Thirty-five patients (90%) completed 4 cycles of chemotherapy.
      Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients
      (36%) experienced grade 3 nonhematologic toxicity. The median increase in
      creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70
      months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after
      completion of therapy. Twelve patients (31%) died, including 11 (28%) with
      recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16
      alterations. In an exploratory analysis, altered expression of p53, p16, and pRB
      was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No
      association between altered p53 and disease-free or overall survival was
      detected, but altered p16 and pRB expression was associated with better outcome
      (P < or = 0.001). CONCLUSION: Gemcitabine/cisplatin with amifostine is tolerated
      in the adjuvant setting for patients with locally advanced bladder cancer. The
      favorable prognostic value of altered p16 and pRB raises the hypothesis of a
      relative beneficial effect of chemotherapy in this population but needs
      verification in other studies.

PMID- 17026805
TI  - Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer.
AB  - BACKGROUND: Docetaxel is the most active single agent in the treatment of hormone
      refractory prostate cancer (HRPC). Because of the preclinical and clinical
      evidence of synergy of capecitabine and docetaxel, it was hypothesized that this
      combination would be active and tolerable in HRPC. PATIENTS AND METHODS: Patients
      received docetaxel 60 mg/m2 intravenously over 60 minutes on day 1 of each 21-day
      cycle and capecitabine 1000 mg/m2 administered orally twice daily on days 1-14 of
      each cycle for a maximum of 8 cycles or until disease progression or intolerable
      toxicity. Seventy-seven patients were enrolled at 43 US Oncology sites. The
      median age was 69.3 years (range, 48-86 years); 86% were white, and the Eastern
      Cooperative Oncology Group performance status scores of 0 and 1 were 49% and 51%
      respectively. Sixty-nine (90%) patients were evaluated for prostate-specific
      antigen response. RESULTS: Overall, 41% of patients had a decreased prostate
      specific antigen level > or = 50%. There were 4 complete responses (6%), 24
      partial responses (35%), 29 incidences of stable disease (43%), and 11 incidences
      of progressive disease (16%). Nine patients has stable disease > or = 6 months
      and the clinical benefit rate was 54%. The median time to response was 1.5 months
      (range, 1-16.9 months). The estimated survival at 12 and 24 months (range, < 1-27
      months). There were no treatment-related deaths. Grade 3/4 toxicities included
      neutropenia (50%), leukopenia (22%), hand-foot syndrome (17%), fatigue (11%), and
      nausea (11%). CONCLUSION: Docetaxel/capcitabine is an active and tolerable
      combination in HRPC. Toxicity was acceptable and anticipated. Response rate and
      survival are comparable with other docetaxel combinations.

PMID- 17026806
TI  - Stromal-epithelial interaction in prostate cancer progression.
AB  - Cancer is not a single-cell disease, and its existence and behavior are
      constantly modulated by the host. Cancer gene expression and genetics are also
      highly dynamic and are regulated epigenetically by the host through gene
      environment interaction. In this article, we describe the molecular pathways
      leading to an unusual property of cancer cells: the ability to mimic the host
      microenvironment and, in particular, the characteristics of osteomimicry and
      vasculogenic mimicry, which are likely to be regulated by soluble and insoluble
      factors in the tumor-adjacent microenvironment. We also discuss the importance of
      host inflammatory and stem cells that contribute to the growth and survival of
      cancer cells. By understanding the salient features of cancer-host interaction,
      novel therapeutics might be developed to target the cancer and its host in the
      treatment of lethal prostate cancer metastases.

PMID- 17026807
TI  - Therapy for stage III non-small-cell lung cancer: Bob Beamon or Chemo-Beamo?

PMID- 17026809
TI  - Aurora kinase inhibitors: a new class of targeted drugs in cancer.
AB  - Aurora kinases (A, B, and C) are essential for spindle assembly, centrosome
      maturation, chromosomal segregation, and cytokinesis. Aurora kinases A and B are
      overexpressed in many cancers, including non-small-cell lung cancer and
      mesothelioma. Small-molecule inhibitors selective for aurora kinases have shown
      promising activity in preclinical tumor models. To date, phase I studies with
      aurora kinase inhibitors have shown that myelosuppression is the dose-limiting
      toxicity, and disease stabilization was achieved in a number of tumor types,
      including non-small-cell lung cancer. Phase II trials are under way in selected
      tumor types. This article reviews the biology of aurora kinases, their potential
      role in the treatment of lung cancer, and challenges in the clinical development
      of this unique class of antineoplastic agents.

PMID- 17026810
TI  - Future trends in patient-reported outcomes assessment for patients with advanced
      stage lung cancer receiving targeted therapy.
AB  - Recent advances in cancer cell biology have led to the development of therapeutic
      agents that target pathways critical to the development and progression of
      disease. These so-called "targeted therapies" might offer patients a more
      tolerable alternative to traditional systemic chemotherapy that often achieves
      therapeutic benefit at the cost of debilitating side effects. Several targeted
      agents have been recently tested in clinical trials of advanced-stage lung
      cancer. As interest in these therapies grows, an understanding of their impact on
      the patient's well-being will be important. Patient-reported outcome measures
      such as formal assessments of health-related quality of life and disease symptoms
      provide a useful means for addressing the impact of therapy from the perspective
      of the patient. We summarize the most commonly used measures of health-related
      quality of life in clinical trials of advanced-stage lung cancer. Although
      existing measurement systems do provide adequate coverage of many important
      patient-related outcome issues, the advent of targeted therapies in advanced
      stage lung cancer does expose several measurement gaps. We highlight some of
      these gaps by reviewing a representative sample of recently conducted clinical
      trials of targeted lung cancer therapy and offer insight as to how these gaps can
      be filled. We also briefly discuss a set of issues unique to patients receiving
      targeted therapy (eg, perceptions of treatment efficacy, treatment compliance,
      patient satisfaction, and treatment convenience) and consider a few methodologic
      concerns unique to patients with advanced cancer.

PMID- 17026811
TI  - Evolving role of interventional pulmonology in the interdisciplinary approach to
      the staging and management of lung cancer: bronchoscopic mediastinal staging of
      lung cancer.
AB  - Mediastinal lymph node involvement is present in 26%-38% of patients with non
      small-cell lung cancer at the time of diagnosis, and it is often the most
      significant factor in determining surgical resectability. Complete and accurate
      mediastinal staging of lung cancer is essential for determining prognosis and for
      guiding optimal treatment strategies. Computed tomography and positron emission
      tomography are the most widely used noninvasive means for mediastinal staging in
      lung cancer. However, based on their reported specificities, computed tomography
      and positron emission tomography findings should be verified by cytohistologic
      sampling. In recent decades, the technique of transbronchial needle aspiration
      (TBNA) has been developed, permitting the bronchoscopist to obtain cytohistologic
      material from the hilar and mediastinal lymph nodes adjacent to the
      tracheobronchial wall. The technique of TBNA has a great specificity, is safe and
      cost-effective compared with surgical methods, and can be performed during the
      initial diagnostic bronchoscopy. Transbronchial needle aspiration sensitivity is
      76%-78% but is highly influenced by several factors. Endobronchial ultrasound has
      been proposed as a means for improving TBNA sensitivity. Recently, a new type of
      bronchoscope with a built-in convex ultrasound probe directly attached to the tip
      has been developed to guide TBNA under real-time imaging. Reports on this
      innovative technique reveal a sensitivity of 94%-95.7%, which is superior to the
      reported sensitivity of surgical methods. However, ultrasound-guided TBNA and
      traditional TBNA should be considered complementary techniques, because their
      integration is likely to become the optimal staging strategy for patients with
      lung cancer.

PMID- 17026812
TI  - Long-term survival with concurrent chemoradiation therapy followed by
      consolidation docetaxel in stage IIIB non-small-cell lung cancer: a phase II
      Southwest Oncology Group Study (S9504).
AB  - PURPOSE: Here we report 5-year survival data from S9504, a Southwest Oncology
      Group phase II trial evaluating consolidation docetaxel after concurrent
      cisplatin/etoposide and thoracic radiation therapy in patients with
      pathologically documented stage IIIB non-small-cell lung cancer. Survival
      outcomes were compared with a predecessor study (S9019) with identical
      eligibility, staging criteria, and treatment, excepting docetaxel consolidation.
      PATIENTS AND METHODS: Treatment consisted of cisplatin 50 mg/m(2) per day on days
      1, 8, 29, and 36; etoposide 50 mg/m(2) per day on days 1-5 and 29-33; and
      concurrent thoracic radiation therapy (total dose, 61 Gy). Consolidation
      docetaxel (75 mg/m(2) initial dose) started 4-6 weeks after completion of
      chemotherapy. RESULTS: Concurrent chemotherapy was generally well tolerated, with
      a low level of radiation-related esophagitis; 2 patients died from pneumonitis.
      Grade 3/4 neutropenia during consolidation docetaxel was common. At a median
      follow-up of 71 months, median progression-free survival was 16 months; median
      survival 26 months; and 3-, 4-, and 5-year survival rates were 40%, 29%, and 29%,
      respectively. Brain metastasis was the most common site of failure. In the
      predecessor trial S9019, median survival was 15 months, and 3-, 4-, and 5-year
      survival rates were 17%, 17%, and 17%, respectively. CONCLUSION: The 5-year
      survival rate in S9540 of 29% compares favorably with the predecessor trial S9019
      and other treatment approaches currently used in this patient population. A phase
      III trial designed to validate the concept of consolidation docetaxel is
      presently under way.

PMID- 17026813
TI  - Phase II trial of sequential chemotherapy followed by chemoradiation, surgery,
      and postoperative chemotherapy for the treatment of stage IIIA/IIIB non-small
      cell lung cancer.
AB  - BACKGROUND: The optimal treatment of locally advanced non-small-cell lung cancer
      remains a challenge. Although the benefit of combined chemoradiation has been
      established, the optimal chemotherapy regimen, timing of full-dose chemotherapy,
      and how best to combine chemotherapy with radiation to maximize systemic and
      radiosensitizing effects remain unclear. PATIENTS AND METHODS: Twenty-nine
      patients with pathologically confirmed stage IIIA/IIIB non-small-cell lung cancer
      were included in a phase II trial of sequential carboplatin/paclitaxel followed
      by chemoradiation, surgery, and postoperative gemcitabine. Twenty-five patients
      (86%) completed the concurrent chemotherapy and radiation therapy phase and were
      eligible for surgery. At restaging, 7 patients (21%) showed disease progression.
      Seventeen patients (59%) went on to surgery. Few were able to tolerate full
      postoperative chemotherapy. RESULTS: The 1-year overall survival rate was 61%,
      with a 2-year survival rate of 56%. Median overall survival was 25.2 months.
      Seven of the patients are alive and without recurrence at the time of this
      writing. Our median follow-up time was 22.2 months. Reversible grade 3/4
      toxicities were fairly common, experienced in 45% of patients. CONCLUSION: Our
      results with this combined modality approach are comparable with those of
      previous, similar studies. Postoperative chemotherapy after initial combined
      modality therapy is often not feasible, reinforcing the value of initial systemic
      therapy. Long-term results are still suboptimal and await studies adding targeted
      therapies to our usual chemotherapy/radiation approaches.

PMID- 17026814
TI  - Topotecan therapy in patients with relapsed small-cell lung cancer and poor
      performance status.
AB  - PURPOSE: Topotecan is generally well tolerated and active in patients with
      relapsed small-cell lung cancer (SCLC) and poor performance status (PS). In this
      study, we investigated whether treatment with topotecan is associated with
      improvement in PS as measured by the rate of conversion from PS 2 to PS 0/1.
      PATIENTS AND METHODS: A retrospective analysis of data from 7 clinical trials (N
      = 795) investigating topotecan in patients with relapsed SCLC was performed. All
      patients received topotecan 1.25-1.5 mg/m2 daily on days 1-5 of a 21-day cycle.
      Demographics were similar for patients with PS 2 and PS 0/1. A total of 152
      patients with PS 2 at baseline received 502 cycles (median, 2 cycles; range, 1-14
      cycles) of therapy, and 32 (21%) experienced PS improvement to PS 0/1 that lasted
      for > or = 2 cycles. RESULTS: Overall, 50% of patients who experienced PS
      conversion also exhibited an objective antitumor response, compared with 8% of
      patients with PS 2 who had no improvement in PS and achieved a response.
      Similarly, median overall survival was longer for patients with PS improvement
      (37 weeks; 95% confidence interval, 29.6-49.4 weeks) compared with patients with
      PS 2 who had a response but no PS improvement (10.4 weeks; 95% confidence
      interval, 8.7-13.6 weeks). A substantial proportion of patients with PS 2 and
      relapsed SCLC experienced PS improvement during topotecan treatment. These
      patients had a substantially longer median survival and a higher response rate
      compared with the overall trial population. CONCLUSION: Improvement in PS appears
      to be a good indicator of benefit from topotecan therapy.

PMID- 17026815
TI  - Randomized, multicenter, open-label phase II study of gemcitabine plus single
      dose versus split-dose carboplatin in the treatment of patients with advanced
      stage non-small-cell lung cancer.
AB  - BACKGROUND: Gemcitabine/carboplatin is a convenient and effective treatment for
      advanced-stage non-small-cell lung cancer (NSCLC), but modification of the
      schedule to diminish thrombocytopenia is worthwhile. PATIENTS AND METHODS: One
      hundred fifty-eight chemotherapy-naive patients with stage IIIB/IV NSCLC were
      randomized from 15 centers in Germany to receive gemcitabine 1250 mg/m(2) on days
      1 and 8 plus carboplatin area under the curve 5 on day 1 (arm A) or carboplatin
      area under the curve 2.5 on days 1 and 8 (arm B), every 21 days for 4 cycles.
      RESULTS: The 2 arms (A vs. B) were well balanced with regard to patient baseline
      characteristics: stage IV 72.5% versus 69%, median Eastern Cooperative Oncology
      Group performance status 1 versus 1. The incidence of grade 3/4 hematologic
      toxicity was as follows (percentage of patients in arm A vs. B): leukopenia 37.5%
      versus 27% (P = 0.075), granulocytopenia 36% versus 36%, and thrombocytopenia 51%
      versus 35% (P = 0.017). Nonhematologic toxicity was modest and comparable with
      both schedules. The overall response rate was 46% versus 36% (P = 0.12), and 24%
      versus 42% had stable disease. Median progression-free survival (5.8 months vs.
      6.1 months) and overall survival (11.7 months vs. 10.7 months) were not
      significantly different between arms A and B. CONCLUSION: Splitting the dose of
      carboplatin between days 1 and 8 on the same days as gemcitabine results in a
      significantly decreased incidence of severe thrombocytopenia, without
      compromising the activity of the combination.

PMID- 17026816
TI  - Cell-free DNA concentration in pleural fluid and serum: quantitative approach and
      potential prognostic factor in patients with cancer and pleural effusions.
AB  - PURPOSE: The presence of pleural effusions in patients with tumors is often
      indicative of locally advanced or metastatic disease, and detection of malignancy
      in effusion samples frequently leads to a disease upstaging. Our purpose was to
      quantify the DNA in pleural effusion and serum in patients presenting pleural
      effusion in order to assess the potential prognostic impact. PATIENTS AND
      METHODS: The DNA level was determined by amplifying hRNase P in paired samples of
      serum and pleural fluid in 70 consecutive patients with cancer showing pleural
      effusion. A group of 30 patients without cancer was included. The correlation
      between serum and pleural DNA was calculated. Survival curves according to serum
      and pleural DNA were analyzed. RESULTS: Median DNA concentrations were greater in
      patients with neoplasia than in patients without malignancy: 105 ng/mL versus 40
      ng/mL (P = 0.001) in serum samples, respectively; 93 ng/mL versus 21 ng/mL (P =
      0.001) in pleural fluids, respectively. A positive correlation between serum and
      pleural levels was confirmed (r = 0.3; P < 0.05). Median survival time for
      patients with serum DNA < or = 105 ng/mL was 11.03 months in contrast to only
      3.63 months for patients with higher values (P = 0.036). Accordingly, median
      survival time for patients with pleural DNA < or = 93 ng/mL was 12.3 months
      versus only 4.63 months in case of higher levels (P = 0.027). CONCLUSION: This
      study shows that there is a strong correlation between higher levels of free DNA
      in pleural fluid or serum and malignancy. Survival is worse for patients with
      higher DNA levels in serum and pleural fluid.

PMID- 17026817
TI  - A multidisciplinary approach to management in a patient with bilateral superior
      sulcus non-small-cell lung carcinoma.
AB  - Superior sulcus tumors comprise a rare subset of non-small-cell lung carcinomas
      that are particularly challenging to treat because of their location and extent
      of nerve and vessel involvement. In this report, we present a case illustrating
      the uncommon situation of a patient presenting with bilateral superior sulcus
      tumors, and we review the latest combined therapeutic approach developed to
      aggressively treat the more common unilateral presentation of these tumors.

PMID- 17026818
TI  - Bortezomib dosing in relapsed multiple myeloma.

PMID- 17026820
TI  - Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation
      inducing ligand in hematologic malignancies.
AB  - B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation
      inducing ligand (APRIL), members of the tumor necrosis family of ligands, are
      expressed by monocytes, macrophages, and dendritic cells, and increased
      expression of these ligands is noted in lymphomas and plasma cell malignancies.
      BLyS and APRIL are essential for the survival of normal and malignant B
      lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell
      maturation, transmembrane activator and calcium-modulating cyclophilin ligand
      interactor, or BAFF-R have been reported in various B-cell malignancies,
      including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's
      lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS
      (in the tumor and in the serum) increased with the transformation of the tumors
      to a more aggressive phenotype. A high BLyS level inversely correlated with a
      poor median overall survival, presence of constitutional symptoms, and increased
      levels of lactate dehydrogenase in patients with non-Hodgkin's lymphoma.
      Additionally, patients who responded to therapy had a lower BLyS level than those
      with progressive disease. Several agents targeting BLyS and APRIL are currently
      being pursued in phase I clinical studies in patients with B-cell malignancies.

PMID- 17026821
TI  - Response to bortezomib and activation of osteoblasts in multiple myeloma.
AB  - Histomorphometry and biochemical markers of bone turnover have shown that,
      although osteoclast activity is increased in multiple myeloma (MM), mostly
      through the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin
      axis, the key element in vivo to determine the presence or absence of osteolytic
      lesions resides on the presence and activity of osteoblasts. The loss of bone
      observed in MM is the result of an uncoupling of bone formation and bone
      resorption. Bortezomib is a first-in-class proteasome inhibitor developed as an
      antineoplastic agent with marked activity in relapsed/refractory MM. Response to
      bortezomib has been related to a significant increase in alkaline phosphatase
      (ALP). Increased ALP in patients responding to bortezomib was associated with a
      parallel increase in bone-specific ALP and parathyroid hormone, suggesting that
      response to bortezomib in MM is closely associated with osteoblastic activation.
      Variation in markers of osteoblastic activation (such as ALP) have also predicted
      response and response duration in patients with myeloma treated with bortezomib
      (P < 0.0001). This clinical observation has been confirmed in an experimental
      mouse model for primary human myeloma. The consequences of increased bone
      anabolism on myeloma growth need to be closely evaluated in prospective trials.

PMID- 17026822
TI  - Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability.
AB  - Follicular lymphoma (FL) is typically characterized by repeated remissions and
      relapses, and many patients receive a number of therapeutic interventions during
      their disease course. Although treatment options are evolving rapidly, stem cell
      transplantation offers a potentially favorable impact on survival. In general,
      many patients with FL are not eligible for this approach by virtue of age and/or
      comorbid disease. Salvage chemotherapy consequently remains the mainstay of
      treatment, being individualized according to disease and patient characteristics,
      goals of therapy, and patient preference. Many of the cytotoxic agents used in
      relapsed FL are highly myelotoxic, leading to significant morbidity and
      mortality, including febrile neutropenia, hemorrhage, and impaired quality of
      life. Nausea and vomiting can also be problematic, particularly with regimens
      incorporating carmustine, cisplatin, and high-dose cyclophosphamide. Other acute
      toxicities include mucositis, alopecia, extravasation injuries, and
      neurotoxicity. Late toxicities can also occur, sometimes months or even years
      after the administration of antineoplastic agents. Acute myeloid leukemias,
      myelodysplastic syndromes, or solid tumors can occur after chemotherapy with
      alkylating agents. The cardiotoxic profile of anthracycline antibiotics is well
      recognized, and several agents, including carmustine and cyclophosphamide, can
      cause lung injury. Persistent neurotoxicity, nephrotoxicity, ototoxicity, and
      vascular toxicity have also been reported in association with chemotherapeutic
      agents used in patients with relapsed FL. Novel therapeutic strategies might
      allow patients to achieve longer remissions, potentially reducing lifetime
      exposure to repeated cycles of chemotherapy and their attendant toxicities. These
      could include the use of more efficient preparative and purging approaches in the
      transplantation setting or the administration of rituximab maintenance therapy
      after (immuno) chemotherapy induction or transplantation.

PMID- 17026823
TI  - Updated guidelines on the management of cytomegalovirus reactivation in patients
      with chronic lymphocytic leukemia treated with alemtuzumab.
AB  - The anti-CD52 monoclonal antibody alemtuzumab is highly active in the treatment
      of chronic lymphocytic leukemia (CLL) in patients with previously treated,
      relapsed, and/or refractory CLL as well as in patients with previously untreated
      disease. The general immunosuppressive impact and toxicities associated with
      alemtuzumab therapy are largely predictable and manageable. In particular,
      cytomegalovirus (CMV) reactivation is now a well-documented complication in
      patients receiving alemtuzumab. This article discusses several strategies for
      monitoring and treating CMV reactivation in patients with CLL receiving
      alemtuzumab-based therapy and provides practical recommendations for CMV
      management by building upon the guidelines published previously in 2004.

PMID- 17026824
TI  - Weekly bortezomib/methylprednisolone is effective and well tolerated in relapsed
      multiple myeloma.
AB  - BACKGROUND: The standard schedule of bortezomib requires frequent infusions and
      is often associated with dose-dependent, adverse effects such as sensory
      neuropathy and thrombocytopenia. Because of the known additive effect between
      bortezomib and glucocorticoid, we explored weekly bortezomib/methylprednisolone
      in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Twenty-nine
      patients were treated at Indiana University with bortezomib (1.3 mg/m2) and
      methylprednisolone (500-2000 mg) intravenously on days 1, 8, and 15 of 28-day
      cycles. Response was evaluated using the Blade criteria. Twenty-one patients
      (70%) had previous stem cell transplantation, and 13 were in third relapse or
      higher. RESULTS: A response was observed in 18 patients (62%): 1 (3%) complete
      response, 1 (3%) near complete response, and 16 (55%) partial responses. Six
      (21%) had stable disease, and 5 (17%) had disease progression. The median time to
      progression, which was defined from the beginning of therapy until progression,
      was 6.6 months (95% confidence interval, 6.4-9.2 months). The median number of
      treatment cycles was 6 (range, 2-12 cycles). The median overall survival was 20.2
      months (lower 95% confidence interval, 13.1 months). The most common toxicities
      were fatigue and gastrointestinal disturbances. Grade >or= 3 adverse effects
      included neuropathy (2 grade 3), gastrointestinal side effects (1 grade 3), and
      congestive heart failure (1 grade 3). CONCLUSION: The weekly
      bortezomib/methylprednisolone regimen was well tolerated and yielded a response
      rate comparable with the standard schedule of bortezomib alone. Our data support
      further investigation of this regimen in larger patient cohorts.

PMID- 17026825
TI  - Immunotherapy with rituximab/interleukin-2 after autologous stem cell
      transplantation as treatment for CD20+ non-Hodgkin's lymphoma.
AB  - BACKGROUND: Relapse of non-Hodgkin's lymphoma (NHL) remains a problem after
      autologous stem cell transplantation (ASCT). Soon after ASCT, the immune system
      is not very active, and this immune incompetence could thus result in decreased
      ability for immune-mediated tumor eradication. The early addition of
      immunotherapy after ASCT might decrease the incidence of relapse and prolong
      survival. In an initial phase I/II trial at our center, the immune modulator
      interleukin-2 (IL-2) increased over baseline natural killer and lymphokine
      activated killer activity in vitro. Because rituximab can lyse CD20-bearing cells
      by antibody-dependent cellular cytotoxicity, adding IL-2 to rituximab might boost
      its effectiveness. It thus seemed reasonable to study this combination after
      ASCT. The results of our phase II study are reported herein. PATIENTS AND
      METHODS: Twenty patients with CD20+ NHL who had ASCT were treated. The median
      time to starting therapy was 79 days (range, 49-100 days) after transplantation.
      RESULTS: The majority of patients reported grade <or= 2 erythema, induration and
      pain at IL-2 injection sites, flu-like symptoms, and worsening fatigue.
      Neutropenia that responded to granulocyte colony-stimulating factor was the most
      common grade 3/4 toxicity, seen in 45% of patients. There were no treatment
      related deaths. Eighteen of 20 patients remain alive in complete remission, with
      a median follow-up of 55.5 months (range, 17-64 months). CONCLUSION: Interleukin
      2/rituximab can be administered after ASCT with manageable toxicity. A randomized
      trial is under way to address whether this combination therapy is beneficial to
      patients with NHL who have had ASCT.

PMID- 17026826
TI  - Response to rituximab in patients with type II cryoglobulinemia.
AB  - Type II cryoglobulinemia (CG) is a heterogeneous, generally indolent disorder
      caused by a monoclonal antibody with activity against polyclonal antibodies and
      is commonly associated with hepatitis C, lymphoproliferative disorders (LPDs), or
      autoimmune diseases. It can lead to substantial morbidity, including renal
      failure, cutaneous ulcers, or neuropathy. Medical records were reviewed for 8
      patients with previously treated symptomatic CG who were part of a prospectively
      held dysproteinemia database. Patients subsequently received 14 total courses of
      rituximab treatment (standard infusion, 375 mg/m2 for 4 or 8 doses) between
      February 1999 and March 2005. One patient had essential CG, and 1 had Gaucher
      disease with hypersplenism. Six patients had an LPD, and 4 of them had
      concomitant disorders (2 with hepatitis C and 2 with Sjogren syndrome). Treatment
      indications included purpura, LPD, cutaneous ulcers, and renal failure. Clinical
      improvement was evaluated by improved cryocrit, total complement, C4, and
      rheumatoid factor. Six patients had some clinical improvement. Cutaneous
      manifestations were the most responsive; renal disease and lymphoma were more
      refractory. Laboratory values showed improvement after 7 of 12 available
      treatment courses. No adverse reactions were noted. Overall, rituximab appears to
      be a safe and effective therapy.

PMID- 17026827
TI  - Scleritis complicating zoledronic acid infusion.
AB  - We present a case of severe unilateral posterior scleritis associated with
      zoledronic acid administration that was recognized and treated in a timely
      manner. Subsequent use of pamidronate was associated with milder inflammation in
      the same eye that eventually resolved with continued monthly infusions,
      indicating the possibility of immunologic tolerance. Physicians prescribing these
      drugs should be aware of this side effect, which, if not recognized and treated
      appropriately, is potentially devastating. We review the published data as well
      as the current treatment recommendations.

PMID- 17026828
TI  - Mycosis fungoides with coccidioidomycosis.
AB  - Mycosis fungoides is an indolent, epidermotropic, cutaneous T-cell lymphoma of
      helper/memory T cells that presents as heterogeneous, papulosquamous patches,
      plaques, and tumors. We present a patient with mycosis fungoides and infection
      with Coccidioides immitis of the skin, which has not been previously reported.

PMID- 17026829
TI  - Engraftment syndrome after hematopoietic stem cell transplantation in multiple
      myeloma.

PMID- 17026830
TI  - EXTEND PIX301: a phase III randomized trial of pixantrone versus other
      chemotherapeutic agents as third-line monotherapy in patients with relapsed,
      aggressive non-Hodgkin's lymphoma.

PMID- 17026831
TI  - Adult mesenchymal stem cells in dental research: a new approach for tissue
      engineering.
AB  - Many adult tissues contain a population of stem cells that have the ability to
      regenerate after trauma, disease or aging. Recently, there has been great
      interest in mesenchymal stem cells and their roles in maintaining the
      physiological structure of tissues. The studies on stem cells are thought to be
      very important and, in fact, it has been shown that this cell population can be
      expanded ex vivo to regenerate tissues not only of the mesenchymal lineage, such
      as intervertebral disc cartilage, bone and tooth-associated tissues, but also
      other types of tissues. Several studies have focused on the identification of
      odontogenic progenitors from oral tissues, and it has been shown that the
      mesenchymal stem cells obtained from periodontal ligament and dental pulp could
      have similar morphological and phenotypical features of the bone marrow
      mesenchymal cells. In fact a population of homogeneous human mesenchymal stem
      cells derived from periodontal ligament and dental pulp, and proliferating in
      culture with a well-spread morphology, can be recovered and characterized. Since
      these cells are considered as candidates for regenerative medicine, the knowledge
      of the cell differentiation mechanisms is imperative for the development of
      predictable techniques in implant dentistry, oral surgery and maxillo-facial
      reconstruction. Thus, future research efforts might be focused on the potential
      use of this cell population in tissue engineering. Further studies will be
      carried out to elucidate the molecular mechanisms involved in their maintenance
      and differentiation in vitro and in vivo.

PMID- 17026832
TI  - Platelet-leukocyte interactions in hemodialysis patients: culprit or bystander?
AB  - The formation of circulating platelet-leukocyte complexes has been observed in a
      variety of conditions and may be pathophysiologically significant. Platelet
      leukocyte interactions in fact facilitate metabolic cooperation and mutual
      activation, which may be of relevance in many biological processes including
      inflammation, atherogenesis and hemostasis. During hemodialysis procedure, the
      series of reactions that can occur upon blood contact with the foreign membrane
      surface may involve a variety of changes affecting almost every cellular and
      plasmatic component of the blood. This article reviews the evidence for abnormal
      interactions between circulating platelets and leukocytes in uremic patients
      undergoing maintenance hemodialysis and the pathophysiologic implications which
      may stem from such interactions.

PMID- 17026833
TI  - A study of the purine derivative AIT-082 in G93A SOD1 transgenic mice.
AB  - AIT-082 is a purine derivative with neuroprotective and neurotrophic activity
      that is desirable in a candidate therapy for Amyotrophic Lateral Sclerosis.
      Consequently, we investigated the effect of AIT-082 in a transgenic mouse model
      of ALS. AIT-082 (0, 1, 3, 10, 30, 60, 100 mg/kg) was given to TgN(SOD1-G93A)1Gur
      transgenic mice from age 30 days until death. The age at onset of clinical signs
      of disease and the age at death were recorded for each animal. Disease
      progression was measured by the weekly average distance run in a running wheel.
      Analysis was made by the Kaplan Meier method with log rank statistics, log rank
      for trend and Cox regression. Neuropathological study of the brain, spinal cord,
      muscles and other organs was undertaken at death. In a second experiment we
      studied the effect of AIT-082 (30 mg/kg) at the onset of disease and during
      survival of transgenic G93A SOD1 mice, beginning dosing at different ages (20,
      30, 40, 60, 80 days). Disease onset was mildly earlier (i.e. worse) at 1 and 10
      mg/kg AIT-082 and mildly delayed at 30 mg/kg. This improvement did not reach the
      usual statistical significance. There was no difference in the age at death for
      any treatment dose. There was no difference in the neuropathology of treated and
      untreated G93A mice. However, there was an early improvement in the running wheel
      function at all tested doses. Using Cox regression, after adjustment for sex, the
      mice in the running wheels had slightly delayed onset of disease without change
      in survival and, after adjustment for exercise, the female mice had slightly
      improved survival. Consequently, AIT-082 would not be an attractive candidate for
      ALS clinical trials as monotherapy and justification for its use in combination
      therapy would require additional laboratory support. There was dissociation
      between the endpoints of disease progression (as judged by running wheel
      performance) and disease onset and survival. AIT-082 improved early running wheel
      performance yet led to accelerated late decline and had no impact on survival. It
      is possible that the drug facilitates early sprouting that leads to accelerated
      late decline.

PMID- 17026834
TI  - Synovial fluid OX40T lymphocytes of patients with rheumatoid arthritis display a
      Th2/Th0 polarization.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease in which T-cell activation
      plays a pivotal role in the induction of articular damage. CD4+/OX40+ T cells
      accumulate in the synovial fluid (SF) of RA patients, which suggests that they
      are involved in the pathogenesis of the disease. In this study, we assessed the
      intracellular cytokine production of peripheral blood and SF CD4+ and CD4+/OX40+
      T cells from RA patients in order to evaluate their role in this disorder. Our
      results show that SF CD4+ cells are predominantly interferon gamma (IFN-gamma)
      positive and express a Th1-like cytokine pattern. In SF, significantly more
      CD4+/OX40+ T cells expressed interleukin-4 (IL-4) and IL4/IFN-gamma than IFN
      gamma alone. Our data demonstrate that SF CD4+/OX40+ T cells express a Th2/Th0
      cytokine profile, which suggests that they are involved in inflammatory responses
      in RA joints.

PMID- 17026835
TI  - Cellular infiltrate and related cytokines, chemokines, chemokine receptors and
      adhesion molecules in chronic autoimmune urticaria: comparison between
      spontaneous and autologous serum skin test induced wheal.
AB  - In recent years, the demonstration of circulating functional autoantibodies
      against the high affinity IgE receptor or against IgE themselves in about one
      third of patients with chronic idiopathic urticaria has suggested that an
      autoimmune mechanism might be involved in the pathogenesis of the disease--the so
      called chronic autoimmune urticaria (CAIU). In this study we compare findings
      from serum-induced and spontaneous wheals with regard to immunohistochemical
      markers of disease activity and discuss whether autologous serum skin test (ASST)
      may be regarded as an in vivo experimental model of the physiological stimulus
      causing urticaria skin condition, or if it does not reproduce the whole of the
      mechanisms operating in the development of spontaneous wheals. By means of
      immunohistochemical technique, we analyzed specimens from just-developed
      spontaneous wheals and from serum-evoked wheals of six CAIU patients, to glean
      information on cellular infiltrate and related cytokines, chemokines, chemokine
      receptors and adhesion molecules. According to the results of our study,
      spontaneous urticaria lesions seem to be sustained by a characteristic
      inflammation pattern where neutrophils, adhesion molecules, IL-8 and chemokine
      receptors play a main role in flogosis triggering and, consequently, disease
      development. On the contrary, ASST-induced wheals seem to imply different
      activities mainly represented by basophil granulocytes and related molecules,
      i.e. IL-4. Although it represents an efficacious diagnostic instrument to screen
      CAIU patients, ASST is not an exhaustive model of the many immunopathogenic
      pathways operating in the development of urticaria lesions, especially with
      regard to systemic activation networks.

PMID- 17026836
TI  - Peroxiredoxin genes are not induced in myeloid leukemia cells exposed to ionizing
      radiation.
AB  - Peroxiredoxins (Prx) comprise an extended family of small antioxidant proteins
      which conserve a thioredoxin-dependent catalytic function that can contribute to
      cell protection from reactive oxygen species (ROS). ROS generation is one of the
      deleterious intracellular effects of ionizing radiation, but the role of Prx
      during radiation treatment has not been extensively explored. Present experiments
      measure effects of ionizing radiation on expression of human Prx types I (PAGA),
      II (NKEF-B) and IV (AOE372) in human myeloid leukemia cells (K562). Prx gene
      transcription was analyzed by amplifying with RT-PCR cDNAs complementary to each
      Prx-specific coding sequence and by identifying the derived products with
      Southern blotting procedure. Transcripts of GAPDH were used as the endogenous
      standard for semi-quantitative comparisons. No consistent increase in Prx gene
      expression was detected at time intervals up to 72 h after gamma radiation doses
      that caused cell cycle arrest and nuclear damage (maximum 20 Gy). Immunoblots
      also were consistent with a prolonged expression or stability of the Prx I/II
      proteins. Similarly, a cytotoxic concentration of the oxidant hemin, which
      stimulates rapid hemoglobinization of K562 cells, caused no induction of Prx gene
      expression. Our results indicate a high Prx stability in human radio-resistant
      leukemia cells.

PMID- 17026837
TI  - Impairment of TNF-alpha production and action by imidazo[1,2- alpha]
      quinoxalines, a derivative family which displays potential anti-inflammatory
      properties.
AB  - In a previous study, we analysed the synthesis and properties of a series of
      imidazo[1,2-alpha]quinoxalines designed in our laboratory as possible imiquimod
      analogues. We found that these imidazo[1,2-alpha]quinoxalines were in fact potent
      inhibitors of phosphodiesterase 4 enzymes (PDE4). PDE4 inhibition normally
      results in an increase in intracellular cAMP which, in PBMC, induces the
      suppression of TNF-alpha mRNA transcription and thus cytokine synthesis. Such an
      effect is antagonistic to that of imiquimod. Furthermore, some TNF-alpha-induced
      activity, such as cell apoptosis which is dependent on the intracellular cAMP
      levels might also be affected. Therefore, by counteracting the properties of TNF
      alpha and/or its production, the imidazo[1,2-alpha]quinoxalines could be
      considered as potential anti-inflammatory drugs. The present study was performed
      to confirm or refute this hypothesis. For this, we characterized the effects of
      imidazo[1,2-alpha]quinoxalines both on TNF-alpha activity and synthesis in regard
      to their ability to act as inhibitors of PDE4 (IPDE4). We found that the
      imidazo[1,2-alpha]quinoxalines dose-dependently prevented the TNF-alpha-triggered
      death of L929 cells, with the 8-series (-NHCH3 in R4) being the most potent.
      Moreover, when the effect of the 8-series on TNF-alpha production was
      investigated using gamma9delta2 T cells, it was observed that these compounds
      impaired the TCR:CD3-triggered TNF-alpha production. Structure-activity analysis
      revealed that these properties of the drugs did not coincide with their IPDE4
      properties. This prompted further exploration into other signalling mechanisms
      possibly involved in TNF-alpha action and production, notably the p38 MAPK and
      the PI3K pathway. We demonstrate here that the imidazo[1,2-alpha]quinoxalines
      targeted these pathways in a different way: they activated the p38 MAPK pathway
      whilst inhibiting the PI3K pathway. Such effects on cell signalling could account
      for the imidazo[1,2-alpha]quinoxalines effects on 1) action and 2) production of
      TNF-alpha, which define these drugs as potential anti-inflammatory agents.

PMID- 17026838
TI  - Melaleuca alternifolia essential oil possesses potent anti-staphylococcal
      activity extended to strains resistant to antibiotics.
AB  - Melaleuca alternifolia Cheel essential oil (TTO) and its major component terpinen
      4-ol were examined against a large number of clinical isolates of Staphylococcus
      aureus to establish their anti-staphylococcal activities. Classic and established
      procedures were used to study M.I.C., time-kill curves, synergism and mutational
      frequency. The anti-staphylococcal activity of terpinen-4-ol and TTO were
      superior to those of antibiotics belonging to the major families (all the tested
      drugs are for topical use or included in ointments, eye drops or used during
      surgery); terpinen 4-ol and TTO were active against strains resistant to
      mupirocin, fusidic acid, vancomycin, methicillin and linezolid. TTO and terpinen
      4-ol were bactericidal as revealed by time-kill curves; the frequency of
      mutational frequency to TTO was < 2.9 x 10 9. The study demonstrates good anti
      staphylococcal activity of TTO and terpinen-4-ol against a large number of
      S.aureus isolates and suggests the possible application of these agents for
      topical treatment of staphylococcal infections. This is the first extensive study
      on the anti-staphylococcal activity of TTO. The results suggest that this
      compound may have application as a topical agent for the control of superficial
      staphylococcal infections, including activity against organisms resistant to
      antibiotics which can be used, or are specific, for topical use.

PMID- 17026839
TI  - In vitro susceptibility of isolates of Borrelia burgdorferi s.l. to antimicrobial
      agents.
AB  - In the present study, we investigate the in vitro antimicrobial activity of
      macrolides, beta-lactams and tetracycline against Borrelia burgdorferi s.l.
      clinical and tick isolates. Minimal inhibitory concentrations (MICs) were
      determined in normal growth condition and after pre-exposure of the strains to
      sub-MIC of the founder of each drug family. All the classes of tested antibiotics
      showed good antibacterial activity against all the borreliae isolates and there
      were no significant susceptibility differences among clinical and tick isolates.
      After pre-exposure of the strains to sub-MIC of erythromycin, cefoxitin and
      tetracycline, we observed that some strains of B. burgdorferi s.l. showed higher
      MIC values to both the pre-exposed drug and drugs of the same family. The less
      susceptibility of borreliae, in the last growth condition in vitro, could be one
      of the justifications of clinical results indicating the limited efficacy of
      these antibiotics in treatment of B. burgdoferi infections.

PMID- 17026840
TI  - In vivo effect of an immunostimulating bacterial lysate on human B lymphocytes.
AB  - The aim of the present study is to investigate in humans the mechanism by which
      the oral vaccine Polyvalent Mechanical Bacterial Lysate (PMBL) can rapidly
      mobilize specific immune response and evaluate the efficacy of its
      immunostimulating activity in preventing recurrent infections of the upper
      respiratory tract (URTIs) in a group of patients with a medical history of URTI
      recurrence. Patients received, by sublingual route, PBML, an immunostimulating
      lysate obtained by mechanical lysis of the most common bacteria responsible for
      upper respiratory tract infections. The treatment was administered for 10
      consecutive days/month for 3 consecutive months. After the end of the treatment
      period the patients were followed up for an additional 3 months. The frequency of
      IgM memory B cells and the expression of the activation marker CD25 in peripheral
      blood lymphocytes were measured using the flow cytometric method before the start
      and at days 30 and 90 of the treatment cycle. To correlate clinical results to
      immunological parameters, the patients were monitored at different time-points
      during the treatment and at the end of follow-up period. The results showed that
      PMBL exerts a therapeutic and preventing effect in acute and recurrent infections
      of the upper respiratory tract and that this effect correlated with the
      activation and enhancement of both IgM memory B lymphocytes (CD24+/CD27+ cells)
      and IL2 receptor-expressing lymphocytes (CD25+ cells) involved either in humoral
      or cellular immunity.

PMID- 17026841
TI  - Non-lethal Candida albicans cph1/cph1 efg1/efg1 transcription factor mutant
      establishing restricted zone of infection in a mouse model of systemic infection.
AB  - The cph1/cph1 efg1/efg1 Candida albicans mutant cells were non-lethal in a mouse
      model of systemic infection. We investigated in vivo proliferation and invasion
      of C. albicans cells in infected mice to elucidate the interaction between the
      host and the pathogen. Homogenates of kidneys from the mice infected with the
      wild-type and the mutant C. albicans cells yielded a mean of 2.1 x 10 7 CFU/g and
      2.2 x 10 6 CFU/g, respectively. The kidneys from the mice infected with the wild
      type cells showed extensive renal cortical necrosis associated with neutrophilic
      infiltration. There were also wild-type hyphal cells present in abundance. Hence,
      tubular necrosis leading to renal failure in the mice may be the cause of death.
      Although the cph1/cph1 efg1/efg1 mutant cells were not lethal, they were capable
      of establishing restricted zones of infection and colonization near the renal
      pelvis instead of simply being cleared by the immune system in mice.

PMID- 17026843
TI  - Chromium (VI)-induced immunotoxicity and intracellular accumulation in human
      primary dendritic cells.
AB  - Chromium compounds, besides being occupational carcinogens, can also induce
      allergic contact dermatitis (ACD) and other immunomodulatory effects. In this
      study we investigate cell viability, uptake and intracellular distribution of
      chromium in human primary dendritic cells (DCs), either immature (iDCs) or driven
      to differentiate by a specific maturation stimulus (LPS) (mature DCs, mDCs), when
      exposed for 48 h to concentrations of soluble radiolabelled Na251CrO4 ranging
      from 5 to 0.5 microM. The modulation of the expression of membrane markers (CD80,
      CD86, MHC class II) correlated with the immunological functions of DCs was also
      measured. After 48 h of exposure the mean IC50 values in 4 donors were 36 and 31
      microM in iDCs and mDC respectively, as detected by propidium iodide
      incorporation. Cellular uptake of chromium was nearly linear with increasing
      doses. At 48 h post-exposure chromium was accumulated preferentially in the
      nuclear and cytosolic fractions (44.1 to 66% and 13.1 to 31% of total cellular
      chromium, respectively). Although a high inter-individual variability was
      observed, an increase in the expression of CD86 and, to a lower extent, CD80 and
      MHC class II membrane markers was found in mDCs of single donors. These results
      highlight the relevance of searching for the biodistribution of trace metals in
      primary cells of the immune system. Moreover, they suggest that DCs
      differentiation markers can help in measuring the immunotoxicity of metal
      compounds with sensitisation potential.

PMID- 17026842
TI  - Discrete MBL-MASP complexes show wide inter-individual variability in
      concentration: data from UK vs Armenian populations.
AB  - Mannan-binding lectin (MBL) circulates in plasma in complex with MBL-associated
      serine proteases (MASP) -1, -2 and -3 and a smaller component, MAp19. When MBL
      binds to the surface of foreign material (microorganisms), MASP-1, -2, -3 are
      activated. MASP-2 then activates the complement system. MASP-1 and -3 may
      activate other (unidentified) systems. MBL levels, MBL-bound MASP-1 and MBL-bound
      MASP-2 activities have been evaluated in healthy individuals from UK and Armenian
      populations. MBL-bound MASP-2 activity declines in aging (P<0.04). MBL correlates
      with smoking (P<0.02). There were significant differences between the two
      populations in MBL-bound MASP-1 activity and in MBL, but no difference in MBL
      bound MASP-2 activity. When MASP activities were normalised to MBL (i.e. MASP-1
      activity/MBL, MASP-2 activity/MBL), normalised MASP-2 activity in UK individuals
      was more than 2 fold higher than in Armenians. The difference in normalised MASP
      2 activity level between these two Caucasoid populations, suggests that
      concentration of the MBL-(MASP-2) complex, and therefore the function of
      activating complement, depends not only on the quantity of MBL in serum and its
      oligomeric state, but also on the quantity of MASP-2 in serum. It is likely that
      in individuals with high MBL concentration there is excess free MBL not occupied
      by MASPs, particularly not by MASP-2.

PMID- 17026844
TI  - A clinical trial of oral hyposensitization in systemic allergy to nickel.
AB  - Nickel allergy is the most common contact allergy. Some nickel-sensitive patients
      present systemic (cutaneous and/or digestive) symptoms related to the ingestion
      of high nickel-content foods, which significantly improve after a specific low
      nickel-content diet. The etiopathogenetic role of nickel in the genesis of
      systemic disorders is, furthermore, demonstrated by the relapse of previous
      contact lesions, appearance of widespread eczema and generalized urticaria-like
      lesions after oral nickel challenge test. The aim of this study is to investigate
      the safety and efficacy of a specific oral hyposensitization to nickel in
      patients with both local contact disorders and systemic symptoms after the
      ingestion of nickel-containing foods. Inclusion criteria for the recruitment of
      these patients were (other than a positive patch test) a benefit higher than 80%
      from a low nickel-content diet and a positive oral challenge with nickel. Based
      on the previous experiences, our group adopted a therapeutic protocol by using
      increasing oral doses of nickel sulfate associated to an elimination diet.
      Results have been excellent: this treatment has been effective in inducing
      clinical tolerance to nickel-containing foods, with a low incidence of side
      effects (gastric pyrosis, itching erythema).

PMID- 17026845
TI  - Non-invasive assessment of airway inflammation in ship-engine workers.
AB  - Smoking is harmful for respiratory function. In young to middle-aged men the
      damage is insidious and difficult to demonstrate. The respiratory impairment
      could increase under specific stressful conditions in the professional
      environment. On the hypothesis that exhaled markers are useful for assessing
      airway susceptibility to inhaled irritants, we measured exhaled markers and lung
      function in smoking and non-smoking engine-driver military coastguards before and
      after a patrol at sea. Eighteen men, mean age 39 yrs (range 23-58 yrs), 8
      smokers, underwent spirometry, exhaled and nasal nitric oxide (eNO, nNO), exhaled
      carbon monoxide (CO) and exhaled breath condensate (EBC) for measures of hydrogen
      peroxide (H2O2), leukotriene B4 (LTB4), proteins (Prots), 8-isoprostanes (8
      IsoPs), nitrite (NO2-) and nitrosothiols (RS-NOs) at baseline and after an 8-hour
      patrol navigation on board small, high-speed diesel-powered ships. At baseline,
      the smokers showed higher middle flows and CO levels, lower eNO and nNO than non
      smokers, but similar levels of EBC markers; geometric means (95% confidence
      interval), CO: 23.6 (14.5 to 38.3) vs. 3.5 (2.5 to 5.3) ppm; eNO: 7.9 (4.8 to
      12.9) vs. 26.7 (15.7 to 45.5) ppb, p=0.000. After navigation, Prots, 8-IsoPs and
      RS-NOs (but not lung function variables or other markers) significantly increased
      only in smokers; baseline vs post-navigation RS-NOs: 0.27 (0.11 to 0.65) vs. 1.30
      (0.58 to 2.89) micromol, p=0.012. The respiratory consequences of a stressing
      environment in engine-driver military coastguards who actively smoke are better
      assessed by measuring EBC markers than by eNO, nNO or lung function. By
      increasing airway inflammation from oxidative-stress, tobacco smoking appears to
      interact with other chemical or physical factors elicited during sea navigation.
      Precisely what these factors are deserves further investigation.

PMID- 17026846
TI  - Deficiency of INFgamma producing cells in adenoids of children exposed to passive
      smoke.
AB  - Exposure to passive smoke is a very common event associated with increased
      susceptibility to respiratory tract infections. Many related adverse effects
      result from the ability of cigarette smoke extracts to interfere with the immune
      system, but the mechanism is not yet completely understood. The aim of the
      present study is to evaluate the intracellular cytokine profile in adenoids and
      peripheral blood cells of children exposed to passive smoke. Children undergoing
      adenoidectomy exposed or not exposed to passive smoke were studied. The
      intracellular cytokine profile of lymphocyte subsets in adenoids and in
      peripheral blood were evaluated by flow cytometry analysis. Children exposed to
      tobacco smoke showed a significantly lower percentage of INF-gamma producing CD4+
      and CD8+ cells in adenoids. Moreover a significant correlation was observed
      between the quantity of exposure and reduction in Th1 (CD4+INFgamma+ and
      CD8+INFgamma+) cells in adenoids. This reduction may be a contributing factor in
      the increasing susceptibility to respiratory tract infection in children exposed
      to tobacco smoke.

PMID- 17026847
TI  - Evidence of lower oxidative stress in the air spaces of patients with reversible
      COPD.
AB  - The mechanism responsible for the reversibility of airflow limitation in stable
      chronic obstructive pulmonary disease (COPD) patients is unknown. The aim of this
      study is to assess the relationship between the reversibility of airflow
      limitation, the redox balance and the inflammatory cells in the sputum of
      patients with stable COPD. For this purpose we examined 15 normal healthy control
      subjects and 20 nonatopic COPD patients. The COPD patients were divided into two
      groups: reversible COPD (increase in FEV1> 200 ml and/or > or =12> or = after 200
      microg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in
      induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL
      4 and IL-6 and TNF-alpha in plasma and sputum. GSH oxidation and protein
      oxidation were lower in reversible COPD patients than in those with no
      reversibility. The sputum eosinophil count was significantly higher in the
      reversible group than in the non-reversible group, and IL-4 concentration was
      higher in the same patients both in sputum and in plasma. In contrast, IL-6 and
      TNF-alpha were increased in non-reversible COPD patients in both biological
      samples. We conclude that airflow reversibility in COPD patients is associated
      with airway oxidative stress and activation of eosinophil inflammatory pattern in
      sputum and blood, suggesting that these patients could respond to specific
      pharmacological treatment.

PMID- 17026848
TI  - Relationship between specific serum IgE to Ascaris lumbricoides and onset of
      respiratory symptoms in Bangladesh immigrants.
AB  - The role of helminths in asthma and/or rhinitis and in allergic sensitization is
      still unclear. We assessed the relationship between Ascaris-specific IgE,
      respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246
      individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE,
      specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological
      evaluation of the stool were performed. Total serum IgE were significantly higher
      in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0-1436.0] kU/L vs.
      207.0 [127.0-332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms
      (413.0 [239.0-1096.0] kU/L vs. 259.5 [147.0-387.0] kU/L), (P < 0.0001), but not
      in SPT positive subjects (413.0 [179.0-894.0] kU/L vs. 404.6 [305.0-1201.0] kU/L
      (P = 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory
      symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P =
      0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and
      Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay
      in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5-19.8], P = 0.007, and
      OR 1.5 [CI 95% 1.3-1.7], P< 0.0001), and with respiratory symptoms (OR 13.7 [CI
      95% 3.0-62.4];, P = 0.0007, and OR 2.4 [CI 95% 1.9-3.0], P < 0.0001). Ascaris-IgE
      were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1-0.8], P =
      0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04-0.7], P = 0.01). Our
      findings favour the role of environmental factors in the development of
      respiratory symptoms in immigrants, irrespective of Ascaris-IgE.

PMID- 17026849
TI  - Immunoinflammatory activation during the acute phase of lacunar and non-lacunar
      ischemic stroke: association with time of onset and diabetic state.
AB  - Several studies have stressed the involvement of inflammation in the
      pathophysiology of acute brain ischemia, but the role of immunoinflammatory
      activation in diabetic stroke patients has not yet been fully evaluated. The aim
      of our study was to evaluate immunoinflammatory activation of acute phase of
      stroke in relation to time of symptoms onset, diabetic state and diagnostic
      subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute
      ischemic stroke and 123 subjects without acute ischemic stroke, and measured
      levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM
      1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24
      72h. Our stroke patients exhibited significantly higher plasma levels of
      cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients
      exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones.
      Lacunar strokes in comparison with those non-lacunar exhibited significantly
      lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic
      patients with lacunar strokes exhibited a minor grade of immunoinflammatory
      activation of the acute phase at 24-72h and 7-10 days after stroke onset. The
      minor grade of immunoinflammatory activation of patients with lacunar strokes,
      particularly diabetic ones, could be related to the minor extension of the
      infarct size, owing to the typical microvascular disease of diabetic subjects
      which could also explain the reported better outcome of this subtype of ischemic
      stroke.

PMID- 17026850
TI  - Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in
      patients with renal diseases.
AB  - It is well known that change in apoptosis may modulate the natural story of
      illness, and that many drugs may act through modulation of apoptosis, but the
      role of steroids in acting through apoptosis in different settings, including
      renal diseases, has still to be elucidated. We studied the in vivo effects of
      steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses
      (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral
      lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79
      subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN,
      19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial
      nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22
      (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A
      significant decrease in CD3+CD8+ cell count and a significant increase of the
      CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA
      fragmentation did not change after oral steroids, paralleling a 22 to 32%
      decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a
      deeper drop of all lymphocyte subsets was observed, while DNA fragmentation
      turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to
      present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the
      presence of apoptosis in renal diseases is associated with decreased CD3+CD8+
      cell count. Furthermore, steroid intravenous pulses, besides inducing a profound
      decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte
      apoptosis, eventually leading to a reversal of baseline patterns, either turning
      from negative to positive or from positive to negative. Oral steroid therapy did
      not influence baseline apoptosis.

PMID- 17026851
TI  - Immunity to extracellular matrix antigens is associated with ultrastructural
      alterations of the stroma and stratified epithelium basement membrane in the skin
      of Hashimotos thyroiditis patients.
AB  - Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and
      V collagens (CI, CIII, CIV, CV), laminin (LM) and fibronectin (FN), as antigen
      sources we detected autoantibodies to conformational and/or denatured ECM
      antigens among 34 of 50 sera obtained from Hashimotos thyroiditis (HT) patients
      and 6 of 51 control sera obtained from non-autoimmune thyroid disease patients
      and healthy donors (HT sera vs. control sera p=4 x 10-9). Reactivity to
      conformational antigens, mostly due to autoantibodies of the IgG isotype, was
      observed in 30/50 HT sera and in 6/51 control sera (p=3.5 x 10-7) and was not
      always concomitant with that to linear antigens, found in 23/50 HT and in 6/51
      control sera (p=1.6 x 10-4). Ultrastructural analysis of skin biopsies obtained
      from 18 HT patients without symptomatic cutaneous diseases revealed defects of
      the stratified squamous epithelium basement membrane in 11/18, alterations of the
      stroma in 13/18 and both basement membrane and stromal defects in 9/18.
      Interestingly, 13/13 (p=0.012) and 9/11 (p=0.012) patients with stromal and
      basement membrane defects respectively, exhibited serum antibodies to at least
      one ECM antigen involved in the organization of the altered tissue compartment.
      Lastly, 10/18 skin biopsies presented immunoglobulin (Ig) and/or complement (C3)
      deposits along the cutaneous basement membrane zone (BMZ) or in the papillary
      dermis and 9/10 sera from the same patients simultaneously showed antibodies to
      at least one ECM antigen involved in the organization of these two skin
      compartments. Besides, 8/11 HT patients with basement membrane defects exhibited
      Ig or C3 deposits along the BMZ. Our findings suggest that autoantibodies to ECM
      molecules might contribute to the development of asymptomatic extra-thyroid skin
      diseases in HT patients.

PMID- 17026852
TI  - Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused
      apoptotic pathway.
AB  - We investigated mRNA expression of the genes involved in the apoptotic mechanism
      in oral squamous cell carcinoma (OSCC) by cDNA microarray. The aim of this study
      was to identify genes mainly involved in tumorigenesis, comparing the difference
      of gene expression in neoplastic and non-neoplastic tissues. Eight frozen samples
      of OSCC and the corresponding normal oral mucosa were treated to obtain mRNA. The
      mRNA extracted from these specimens was converted into cDNA and analyzed with
      SuperArray GEArray Q Series Human Apoptosis Gene Array kit. Our results showed
      that in OSCC there is a different expression of CRADD, FADD, ATM and APAF-1 genes
      compared to normal mucosa. Real-Time PCR, and Western blot analysis were
      performed on a separate cohort of patients in order to confirm the results
      obtained by DNA microarray. Our analysis of apoptotic process through microarray
      technology confirmed that different molecules could be responsible or favour the
      imbalance of apoptosis in cancer tissues. Microarray technology has made it
      possible to analyze the expression of multiple genes in a single experiment.
      However, most commercial array kits, designed to include as many genes as
      possible, produce a vast amount of data that often is difficult to interpret. In
      addition, the cost of equipment is often prohibitive. In contrast, the focused
      kit used was a complete, affordable and effective method to improve knowledge of
      molecular specific pathways.

PMID- 17026853
TI  - The role of calcium and magnesium ions in uptake of beta-amyloid peptides by
      microglial cells.
AB  - Amyloid peptides 1-40 and 1-42 (Abeta 1-40 and Abeta 1-42) are major components
      of diffuse and neuritic senile plaques present in the brain of patients with
      Alzheimers disease. Their interaction with microglial cells was studied using a
      system partly mimicking these plaques, which consisted in heat-killed yeast
      particles coated with either Abeta 1-40 or Abeta 1-42. Using these particles, it
      has been shown in our laboratory that LRP is involved mainly in the elimination
      of Abeta 1-42-coated heat-killed yeast particles and partly in that of Abeta 1-40
      coated heat-killed yeast particles by microglial cells in culture. We show here
      that in the presence of calcium and magnesium ions extracellular chelators,
      namely EDTA (for both ions) and EGTA (for calcium ions), the internalization of
      coated heat-killed particles was impaired. In the presence of BAPTA-AM, an
      intracellular chelator of calcium ions and thapsigargin, an inhibitor of the
      endoplasmic reticulum calcium pump, no effect was observed on the phagocytosis of
      Abeta 1-40-coated heat-killed yeast particles, whereas that of Abeta 1-42-coated
      heat-killed yeast particles was affected. These results suggest that different
      signaling mechanisms are involved after the internalization of Abeta 1-40 and
      Abeta 1-42.

PMID- 17026854
TI  - Neonatal eating epilepsy: pathophysiological and pharmacologic aspects.
AB  - We report a case of neonatal Eating Epilepsy. The baby was admitted to the
      Neonatal Intensive Care Unit of Chieti after delivery, with respiratory distress
      syndrome. In the first day of life the baby had an episode of arterial
      desaturation and cyanosis with EEG alterations. After laboratory and instrumental
      investigations we found a correlation between EEG abnormalities and GER. So we
      administered a combination of anticonvulsive and antacid therapy and, considering
      the total improvement of EEG, we diagnosed a neonatal form of "eating epilepsy".

PMID- 17026856
TI  - Study of the morphology and biomechanics of sacral fracture.
AB  - OBJECTIVE: To observe the morphological characteristics of sacral fracture under
      different impact loads. METHOD: Ten fresh pelvic specimens were loaded in dynamic
      or static state. A series of mechanical parameters including the pressure strain
      and velocity were recorded. Morphological characteristics were observed under
      scanning electron microscope. RESULTS: The form of sacral fracture was related to
      the impact energy. Under low energy impact loads, ilium fracture, acetabulum
      fracture and crista iliaca fracture were found. Under high energy impact loads,
      three types of sacral fracture occurred according to the classification of Denis:
      sacral ala fracture, Type I fracture; sacral foramen cataclasm fracture, Type II
      fracture; central vertebral canal fracture, Type III fracture. Nerve injury of
      one or two sides was involved in all three types of sacral fracture. The fracture
      mechanism of sacrum between the dynamic impact and static compression was
      significantly different. When the impact energy was above 25 J, sacral foramen
      cataclasm fracture occurred, involving nerve root injury. When it was below 20 J,
      ilium and sacral fracture was most likely to occur. When it was 20 approximately
      25 J, Type I fracture would occur. While in the static test, most of the fracture
      belonged to ilium or acetabulum fracture. The cross section of sacrum was crackly
      and the bone board of Haversian system was brittle, which could lead to
      separation of bone boards and malposition of a few of cross bone boards.
      CONCLUSIONS: In dynamic state, sacrum fracture mostly belongs to Type I and Type
      II, and usually involves the nerve roots. Sacrum fracture is relevant to the
      microstructures, the distribution of the bone trabecula, the osseous lacuna and
      the Haversian system of sacrum. The fracture of ilium and acetabulum more
      frequently appears in static state, with slight wound of peripheral tissues.

PMID- 17026855
TI  - TIMP-1 is a key factor of fibrogenic response to bleomycin in mouse lung.
AB  - Pulmonary fibrosis is characterized by the excessive deposition of extracellular
      matrix in the interstitium, resulting in respiratory failure. The role of
      remodeling mediators such as metalloproteinases (MMPs) and their inhibitors
      (TIMPs) in the fibrogenic process remains misunderstood. We investigated MMP-9,
      MMP-2, TIMP-1, TIMP-2 and TIMP-3 in the fibrotic response to bleomycin of
      fibrosis prone C57BL/6J and fibrosis resistant BALB/c mice. Mice were
      administered with 0.1 mg bleomycin by intranasal administration. Either 24 h or
      14 days after, the mice were anesthetized and underwent either bronchoalveolear
      lavage (BAL) or lung removal. Collagen deposition in lung tissue was determined
      by hydroxyproline measurement, MMP activity was analyzed by zymography, and other
      mediators were analyzed by ELISA. TIMP-1 was localized in lung sections by
      immunohistochemistry and real time PCR was performed to gene expression in lung.
      Non parametric Mann-Whitney and Spearman tests were used for statistical
      analysis. Fourteen days after bleomycin administration, hydroxyproline assay and
      histological study revealed that BALB/c mice developed significantly less
      fibrosis compared to C57BL/6J mice. At day 1, bleomycin enhanced TIMP-1, MMP-2
      and MMP-9 protein levels in BALF, and induced corresponding genes in lung tissue
      of both strains. The rise of Timp-1, Mmp-9 and Mmp-2 gene levels were
      significantly stronger in lungs of C57BL/6J, whereas gelatinase activities of MMP
      2 and MMP-9 were similar. Immunohistochemistry revealed that TIMP-1 macrophages
      and epithelial cells were prominent TIMP-1 producers in both strains. At day 14,
      neither MMP-2 nor MMP-9 levels exhibited strain-dependent protein level or gene
      expression, although TIMP-1 was strongly associated with fibrosis. Interestingly,
      bleomycin induced neither Timp-2 nor Timp-3 in lung tissue at any time of the
      study. The present study shows that early altered regulation of TIMP-1 following
      bleomycin administration may be involved in bleomycin-induced pulmonary fibrosis.

PMID- 17026857
TI  - Repairing articular cartilage defects with tissue-engineering cartilage in
      rabbits.
AB  - OBJECTIVE: To investigate the effect of cancellous bone matrix gelatin (BMG)
      engineered with allogeneic chondrocytes in repairing articular cartilage defects
      in rabbits. METHODS: Chondrocytes were seeded onto three-dimensional cancellous
      BMG and cultured in vitro for 12 days to prepare BMG-chondrocyte complexes. Under
      anesthesia with 2.5% pentobarbital sodium (1 ml/kg body weight), articular
      cartilage defects were made on the right knee joints of 38 healthy New Zealand
      white rabbits (regardless of sex, aged 4-5 months and weighing 2.5-3 kg) and the
      defects were then treated with 2.5% trypsin. Then BMG-chondrocyte complex (Group
      A, n=18), BMG (Group B, n=10), and nothing (Group C, n=10) were implanted into
      the cartilage defects, respectively. The repairing effects were assessed by
      macroscopic, histologic, transmission electron microscopic (TEM) observation,
      immunohistochemical examination and in situ hybridization detection,
      respectively, at 2, 4, 8, 12 and 24 weeks after operation. RESULTS: Cancellous
      BMG was degraded within 8 weeks after operation. In Group A, lymphocyte
      infiltration was observed around the graft. At 24 weeks after operation, the
      cartilage defects were repaired by cartilage tissues and the articular cartilage
      and subchondral bone were soundly healed. Proteoglycan and type II collagen were
      detected in the matrix of the repaired tissues by Safranin-O staining and
      immunohistochemical staining, respectively. In situ hybridization proved gene
      expression of type II collagen in the cytoplasm of chondrocytes in the repaired
      tissues. TEM observation showed that chondrocytes and cartilage matrix in
      repaired tissues were almost same as those in the normal articular cartilage. In
      Group B, the defects were repaired by cartilage-fibrous tissues. In Group C, the
      defects were repaired only by fibrous tissues. CONCLUSIONS: Cancellous BMG can be
      regarded as the natural cell scaffolds for cartilage tissue engineering.
      Articular cartilage defects can be repaired by cancellous BMG engineered with
      allogeneic chondrocytes. The nature of repaired tissues is closest to the normal
      cartilage. Local administration of trypsin can promote the adherence of repaired
      tissues to host tissues. Transplantation of allogeneic chondrocytes has
      immunogenicity, but the immune reaction is weak.

PMID- 17026858
TI  - Treatment of chronic osteomyelitis with one-stage allograft.
AB  - OBJECTIVE: To avoid disadvantages of two-stage cancellus bone autograft, we
      investigated the feasibility of one-stage allograft for reconstructing the bone
      defect resulting from debridement of chronic osteomyelitis in limbs. METHODS:
      Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of
      nonunion) underwent one-stage allograft after debridement in our hospital.
      RESULTS: Thirty-five cases were followed up for an average period of 28 months
      (range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and
      3 cases (8.57%) were confirmed recurrence of infection. Four out of 8 cases of
      bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and
      another case also acquired union after redebridement and autograft of ilium due
      to infection recurrence 35 days after surgery. Renonunion occurred in 3 cases, 2
      out of whom healed after secondary operation with autograft. One case of
      renonunion and 2 cases of infection recurrence refused further treatment.
      CONCLUSIONS: A high rate of infection arrest can be attained when one-stage
      allograft is used to reconstruct the bone defect of chronic osteomyelitis after
      debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as
      a contraindication to one-stage allogeneic bone grafting. Renonuion, however,
      achieves a relatively high rate, especially in cases of segmental bone defect.

PMID- 17026859
TI  - Bcl-2 gene therapy for apoptosis following traumatic brain injury.
AB  - OBJECTIVE: To investigate the therapeutic effect of Bcl-2 fusion protein on
      apoptosis in brain following traumatic brain injury. METHODS: Bcl-2 gene was
      cloned by RT-PCR. Bcl-2 and EGFP genes were linked together and inserted into
      pAdeno-X vector. This recombinant vector was packaged into infectious adenovirus
      in HEK293 cells. Ninety Wistar rats were assigned randomly into experimental
      group (n=45) and control group (n=45). All rats were subjected to traumatic brain
      injury. Then recombinant adenovirus (for experimental group) or saline (for
      control group) was injected into the traumatic brain. The expression of Bcl-2
      fusion protein was investigated by Western blotting, immunohistochemistry and
      fluorescence microscopy. Apoptosis in the injured brain was studied by TUNEL.
      Animals' behavior capacity was evaluated by tiltboard test. RESULTS: In the
      experimental group, many fluorescent cells were found around the traumatic locus,
      which were also proven to be Bcl-2 positive by immunohistochemistry. On the
      contrary, few Bcl-2 positive cells and no fluorescent cell were detected in the
      control group. Bcl-2 expression of experimental group was much higher than that
      of control group, which was illustrated by Western blotting. The apoptosis index
      of experimental group was 0.027+/-0.005, and that of control group was 0.141+/
      0.025 (P < 0.01). Two weeks after injury, animals of the experimental group
      behaved better than those of the control group. CONCLUSIONS: A recombinant
      adenovirus vector expressing Bcl-2 fusion protein has been constructed. Bcl-2
      fusion protein can suppress apoptosis and promote cell survival. Moreover, the
      behavior recovery of the injured animal is promoted. Bcl-2 fusion protein
      provides a way to track the target cells in vivo.

PMID- 17026860
TI  - Clinical analysis of hydroxyapatite orbital implantation after ocular trauma in
      211 cases.
AB  - OBJECTIVE: To evaluate the therapeutic effects and complications of
      hydroxyapatite (HA) orbital implantation on patients after trauma-related
      surgeries. METHODS: Retrospective analysis was made from 211 cases (211 eyes) who
      underwent HA orbital implant placement after trauma-related enucleation or
      evisceration, including 68 cases of evisceration and primary HA implant
      placement, 77 cases of enucleation and HA implant placement wrapped with multi
      windowed sclera, 66 cases of enucleation and HA implant placement free of
      wrapping. All the cases were followed up for 1-5 years to observe the therapeutic
      effects and major complications. RESULTS: Five of 211 cases had wound dehiscence.
      Ten cases had HA implants exposure, including 1 case suffering severe orbital
      infection and requiring HA implant removal. The implants exposure incidences by
      the three surgical methods were from 1.30% to 10.06% and averaged 4.74%.
      Significant difference was found in late exposure incidence and total incidence
      from the three methods (chi(2)=13.372, P < 0.01 and chi(2)=7.540, P < 0.05). Two
      cases had shrinkage of the lower fornix. Enophthalmos occurred in 1 case treated
      by method 1 and was corrected by implanting porous polyethylene (Medpor) plate
      into the bottom of orbit. In 210 cases, the artificial eye moved well and the
      cosmetic results were satisfactory. CONCLUSIONS: Different surgical methods have
      their own merit and disadvantage. Enucleation and placement of HA implant wrapped
      with multi-windowed sclera has corroborated fewer complications than others.

PMID- 17026861
TI  - Biomechanical and clinical study on screw hook fixation after direct repair of
      lumbar spondylolysis.
AB  - OBJECTIVE: To evaluate the biomechanical effect and clinical results of hook
      screw fixation after direct repair of lumbar spondylous defects in the pars
      interarticularis. METHODS: L(2)-L(6) spines of 8 fresh-frozen and thawed calf
      cadavers were used for mechanical testing. Bilateral spondylous defects were
      created in the L(4)vertebra. The intervertebral rotation ranges between L(4) and
      L(5) were scanned and computerized in various states of motion, such as
      flexion/extension, lateral bending and torsional loadings applied on the intact
      spine and the spondylous spine when the spondylous spine was fixed with modified
      Scott's fixation, hook screw fixation and Buck's fixation sequentially and
      respectively. Between July 2002 and February 2004, 14 young male patients (aged
      15-31 years) suffering from symptomatic lumbar spondylolysis were treated with
      TSRH hook screw fixation after direct repair of the defects. MacNab criteria were
      used to assess their pre-and post-operative status. RESULTS: Each fixation
      technique could significantly increase the intervertebral rotational stiffness
      and made the stiffness return to nearly the intact level. Hook screw technique
      provided more rotational stability than the others. Hook screw and Buck's
      techniques provided more flexion/extension stability than modified Scott's
      technique. Neither complication nor instrumental failure was observed in this
      study. The mean follow-up period was 21 months. All the patients except one
      acquired union during the follow-up period. Thirteen patients had a "good" or
      "excellent" result according to MacNab criteria. CONCLUSIONS: Hook screw fixation
      shows biomechanical advantages and is safe and effective for young patients with
      lumbar spondylolysis.

PMID- 17026862
TI  - Gene damages of mitochondrial DNA encoding cytochrome oxidase of intestinal
      epithelial cells in hemorrhagic shock rats.
AB  - OBJECTIVE: To investigate the detrimental effects of hemorrhagic shock on the
      structure and function of mitochondria DNA (mtDNA) encoding cytochrome oxidase
      genes in intestinal epithelial cells. METHODS: Wistar rats were used and divided
      into two groups: hemorrhagic shock group and control group. Hemorrhagic shock
      model of rats was utilized in this experiment. The mtDNA was extracted from the
      intestinal epithelial cells and amplified by polymerase chain reaction (PCR) with
      different primers of cytochrome oxidase (COX I, COX II and COX III). The products
      of PCR were directly sequenced. RESULTS: Hemorrhagic shock could result in the
      point mutagenesis in mitochondrial genome encoding cytochrome oxidase (COX I and
      COX II). There were 4, 4, 22, 16, 35 point mutations in COX I from 5545 to 6838
      bp in 5 shocked rats. There were five point mutations in COX II from 7191 to 7542
      bp at the site of t7191c, t7212c, a7386g, a7483g, c7542g in 1 shocked rat. There
      was no mutation found in COX III. CONCLUSIONS: Hemorrhagic shock could
      significantly induce the damage of the gene of cytochrome oxidase encoded by
      mtDNA.

PMID- 17026863
TI  - Repair of the radial defect of rabbit with polyester/tricalcium phosphate
      scaffolds prepared by rapid prototyping technology.
AB  - OBJECTIVE: To evaluate the effects of repairing rabbit radial defects with
      polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology
      loaded with bovine bone morphogenetic protein (bBMP), and find new carriers for
      growth factors. METHODS: Polyester/tricalcium phosphate scaffolds prepared by
      rapid prototyping technology loaded with and without bovine BMP were used to
      repair the 15 mm radial defect in rabbit. Then the results of radiography,
      histology, scaffolds degrade rates and bone mineral density (BMD) were appraised
      to examine the effects at the 12th week. RESULTS: At the 12th week
      postoperatively, all defects treated with bBMP were radiographically repaired. No
      radius implanted polyester/tricalcium phosphate scaffolds without bBMP showed
      radiographic and histological union. At experimental groups, longitudinal
      alignment of lamellar structure was observed histologically at the 12th week,
      indicating that remodeling of regenerated bone was complete in different degree.
      Of the three experimental groups, the bony regeneration and remodeling of callus
      in poly lactide-co-glycolide/tricalcium phosphate (PLGA/TCP) group was the best.
      The BMD values were beyond 70% of normal value at the 12th week while the
      PLGA/TCP scaffolds group was the highest, and no abnormalities were observed in
      the surrounding soft tissue in all groups. CONCLUSIONS: Polyester/tricalcium
      phosphate scaffolds prepared by rapid prototyping technology loaded with bovine
      BMP can repair a 15 mm radial defect of rabbit. As for the results, the PLGA/TCP
      scaffold is ideal and better than poly L-lactide-co-D, L-lactide (PDLLA/TCP)
      scaffold, but the ploy L-lactic acid (PLLA/TCP) is not so good for its low
      degradation rates.

PMID- 17026864
TI  - Antioxidation of quercetin against spinal cord injury in rats.
AB  - OBJECTIVE: To observe the effect of quercetin on experimental spinal cord injury
      (SCI) in rats. METHODS: Sixty Sprague-Dawley rats were randomly divided into four
      groups: Group A only for laminectomy, Group B for laminectomy with SCI, Group C
      for SCI and intraperitoneal injection with a bolus of 200 mg/kg quercetin and
      Group D for SCI and intraperitoneal injection of saline. SCI model was made by
      using modified Allen's method on T(12). Six rats of each group were killed at 4 h
      after injury and the levels of free iron and malondialdehyde (MDA) of the
      involved spinal cord segments were measured by bleomycin and thiobarbituric acid
      (TBA) assays separately. The recovery of hind limb function was assessed by
      Modified Tarlov's scale and inclined plane method at 7 d, 14 d and 21 d after
      SCI. The histological changes of the damaged spinal cord were also examined at 7
      d after SCI. RESULTS: After SCI, the levels of free iron and MDA were
      significantly increased in Groups B and D, while not in Group C. The Modified
      Tarlov's score and the inclined plane angles were significantly decreased in
      Groups B, C and D. The histological findings were not improved. CONCLUSIONS:
      After SCI, quercetin can reduce the level of lipid peroxidation, but not improve
      recovery of function.

PMID- 17026865
TI  - Progress of cellular dedifferentiation research.
AB  - Differentiation, the stepwise specialization of cells, and transdifferentiation,
      the apparent switching of one cell type into another, capture much of the stem
      cell spotlight. But dedifferentiation, the developmental reversal of a cell
      before it reinvents itself, is an important process too. In multicellular
      organisms, cellular dedifferentiation is the major process underlying
      totipotency, regeneration and formation of new stem cell lineages. In humans,
      dedifferentiation is often associated with carcinogenesis. The study of cellular
      dedifferentiation in animals, particularly early events related to cell fate
      switch and determination, is limited by the lack of a suitable, convenient
      experimental system. The classic example of dedifferentiation is limb and tail
      regeneration in urodele amphibians, such as salamanders. Recently, several
      investigators have shown that certain mammalian cell types can be induced to
      dedifferentiate to progenitor cells when stimulated with the appropriate signals
      or materials. These discoveries open the possibility that researchers might
      enhance the endogenous regenerative capacity of mammals by inducing cellular
      dedifferentiation in vivo.

PMID- 17026866
TI  - Clinical significance of scoring system for systemic inflammatory response
      syndrome.
AB  - The concepts of systemic inflammatory response syndrome (SIRS) and scoring system
      were defined by the journal of Bone in 1992. SIRS was described as occurrence of
      two or more clinical criteria in four ones (fever or hypothermia, tachypnea,
      tachycardia, and leukocytosis). An early diagnosis and estimation of systemic
      inflammation in patients is helpful for treatment selection. This paper reviews
      the application of SIRS scoring system, which has been extensively validated for
      large groups of critical care patients with severe injury and critical surgical
      diseases. Recent studies have documented SIRS score as a significant predictive
      parameter of adverse outcome in critical care patients. Furthermore, some studies
      also give us a suggestion on how to reduce the overload systemic response.

PMID- 17026867
TI  - Atopic eczema.

PMID- 17026871
TI  - Evidence-based allergy diagnostic tests.
AB  - Effective management of allergic diseases relies on the ability to make an
      accurate diagnosis. Although clinicians rely on experience obtained over many
      years of practice, such experience is anecdotal and unique to the individual
      using it. The result is a tendency for patients with similar clinical
      presentations to receive different diagnoses and treatment, depending on which
      provider they happened to see. The probability that a patient has a particular
      diagnosis can be determined using a combination of diagnostic tests. To make the
      best use of tests, it is important to understand their performance
      characteristics in terms of reproducibility and likelihood ratios. A test that is
      reproducible but that does not predict the presence of a disease is not helpful,
      nor is an accurate test that is not reproducible. To improve the reproducibility
      of diagnostic tests, it is important that proficiency testing be instituted for
      both skin and in vitro tests so that the coefficient of variance can be
      determined. This has already been done for the latter and needs to be done for
      skin tests as well. With use of a combination of history and appropriate
      diagnostic tests, the probability that a particular diagnosis is present can be
      increased or decreased sufficiently either to confirm it or to rule it out. As
      proficiency testing of allergy tests becomes more common and the use of tests
      becomes more consistent, we believe that patients with allergic diseases will
      benefit.

PMID- 17026872
TI  - Childhood asthma in the emergency department: trends, challenges, and
      opportunities.
AB  - Acute exacerbations of childhood asthma are frequently managed in the emergency
      department (ED). ED-based surveillance and intervention projects highlight the
      limitations and challenges of acute and chronic childhood asthma management.
      Because a significant number of asthmatic children currently receive and will
      likely continue to seek acute asthma care in the ED, provision of asthma
      education and initiation of controller medication therapy during the ED visit,
      although controversial, may contribute to improving asthma outcomes and
      eventually to reducing the burden of asthma on our overcrowded EDs.

PMID- 17026874
TI  - Eosinophilic disorders in children.
AB  - Many pediatric diseases demonstrate blood or tissue eosinophilia. Included among
      these disorders are common atopic diatheses such as asthma as well as the rarer
      conditions of hypereosinophilic syndrome and eosinophilic gastrointestinal
      disorders. Eosinophil trafficking and activation in target organs leads to tissue
      damage and ongoing reparative attempts that can ultimately result in changes in
      organ structure and function. Recent treatment with biologic agents such as
      tyrosine kinase inhibitors and anti-interleukin-5 has offered new therapeutic
      options in certain eosinophilic disorders. Eosinophilic disorders such as
      eosinophilic esophagitis are increasingly being diagnosed in children, but many
      lessons in disease pathogenesis, diagnosis, optimal treatment, and natural
      history continue to be learned.

PMID- 17026873
TI  - Immunodeficiency in childhood.
AB  - Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of
      human immunity and hypersensitivity. New discoveries in common variable
      immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways
      of importance in human antibody production. FOXP3 mutations demonstrate the
      essential role that T-regulatory cells play in controlling autoantibody formation
      and disease. Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the
      key role that innate immunity plays in the defense of bacterial disease occurring
      early in life. With respect to therapy, subcutaneous immunoglobulin treatment may
      indeed be a better treatment than intravenous immunoglobulin for many patients
      with antibody deficiency. Finally, PIDs remain in the vanguard for the treatment
      of inherited disorders by gene therapy. Gene therapy has cured patients with
      chronic granulomatous disease and severe combined immunodeficiency, but not
      without morbidity and mortality. Into the 21st century, PIDs continue to instruct
      us in human health and disease.

PMID- 17026876
TI  - Advances in imaging of the paranasal sinuses.
AB  - Imaging technology has played a significant role in the diagnosis and management
      of sinonasal disorders. Plain sinus films are almost exclusively replaced by CT
      in the work-up for inflammatory sinus disease. MRI provides complementary
      information to CT in cases of sinonasal and skull-base neoplasms. The evolution
      of endoscopic surgical techniques for the paranasal sinuses and skull base is
      made possible by the parallel advancement of imaging technologies. Recent
      advances that are currently in clinical use have included multidetector row CT
      scanners and computer image-guidance systems for surgery. Three-dimensional CT
      angiography, image-guided CT-MR fusion, and intraoperative image-guidance are new
      techniques that are currently being evaluated. As imaging technology continues to
      advance, so does the capability to treat diseases beyond the sinuses and skull
      base with minimally invasive, endoscopic approaches.

PMID- 17026875
TI  - The relationship between rhinosinusitis and asthma sinusitis.
AB  - Chronic sinusitis comprises numerous disorders characterized by inflammation,
      mucous gland hyperplasia, and remodeling. Chronic hyperplastic eosinophilic
      sinusitis (CHES) is characterized by unrestrained proliferation of eosinophils,
      Th2-like lymphocytes, fibroblasts, goblet cells, and mast cells. The pathology of
      CHES is similar to that of asthma, and it is frequently diagnosed in association
      with asthma. It has been reported that exacerbations of CHES occur temporally
      with worsening of asthma; however, in the absence of well-controlled studies,
      this linkage remains unproven. In this article, the potential mechanisms linking
      these two diseases are examined.

PMID- 17026877
TI  - Rhinosinusitis in children.
AB  - Clinical practice guidelines for the management of acute bacterial rhinosinusitis
      in children were published by the American Academy of Pediatrics in 2001. Changes
      in the antibiotic susceptibility patterns for the common pathogens causing both
      acute and chronic rhinosinusitis warrant a reevaluation and update of these
      recommendations. In addition, there was only a very brief discussion of chronic
      disease in this publication, with the conclusion that the pathogenesis and
      management of recurrent or prolonged infection were essentially unknown. Although
      there are still insufficient data in the literature to develop evidence-based
      clinical guidelines, a careful review of recent literature and the clinical
      experience of experts who manage pediatric chronic sinusitis are presented in an
      effort to provide some specific recommendations and to offer practical treatment
      options. Factors associated with chronic rhinosinusitis should be addressed
      individually and include environmental pollution, recurrent viral upper
      respiratory infections, allergic and nonallergic rhinitis, ciliary dyskinesia,
      cystic fibrosis, immunodeficiency, gastroesophageal reflux, and anatomic
      abnormalities.

PMID- 17026878
TI  - Primary ciliary dyskinesia and upper airway diseases.
AB  - Primary ciliary dyskinesia (PCD) is a rare and difficult-to-diagnose disease with
      morbidity related to infections of the upper and lower respiratory tract. The
      disease is caused by mutations in genes that are required for proper ciliary
      function. The defect in ciliary function results in reduced or absent mucociliary
      clearance, thereby predisposing the affected individual to repeated bacterial
      infections. Recent advances in the understanding of the basic biology and
      function of the cilium have led to the identification of some of the genes that
      are mutated in cases of PCD. Further studies of this disease will likely lead to
      earlier diagnosis, better treatment, and improved outcomes.

PMID- 17026879
TI  - Dust mite allergen avoidance as a preventive and therapeutic strategy.
AB  - Asthma is a global health problem with genetic and environmental components.
      Indoor allergens have a major impact on asthma, and exposure in sensitized
      subjects can compromise lung function. A reduction in allergen exposure would
      seem a logical facet to treatment. Methods for reducing mite allergen levels that
      are effective in the laboratory may not work in the home and may not result in a
      clinical benefit. Six ongoing studies are investigating the effects of
      environmental control on the primary prevention of asthma and allergies. Although
      the Isle of Wight and Canadian studies provide encouraging results at age 8 and 7
      years, respectively, it will be some time before a definitive public health
      message emerges. For secondary prevention, there is little evidence to support
      the use of mite-proof encasings as a single intervention in adults. In children,
      however, single or multifaceted interventions appear to be of some benefit.

PMID- 17026880
TI  - Principles and clinical application of the locking compression plate (LCP).
AB  - The principle of the locking compression plate (LCP) is represented by the
      combination of two completely different anchorage technologies and two opposed
      principles of osteosynthesis in one implant it combines the principles of
      conventional plate osteosynthesis for direct anatomical reduction with those of
      bridging plate osteosynthesis. Since the LCP can be used as a conventional plate
      using only dynamic compression, as a pure internal fixator using locking head
      screws, or as both combined, it provides the surgeon with multiple variations.
      Nevertheless, these new possibilities mean that preoperative planning and an
      understanding of the different biomechanical principles of osteosynthesis are
      essential if good clinical outcomes are to be achieved and maximum benefit is to
      be attained from the options offered by the LCP system. The current article
      provides biomechanical background to and guidelines for the use of LC plates in
      the operative treatment of fractures and also reports experimental and clinical
      results obtained with LCP.

PMID- 17026881
TI  - [Current strategies for prevention of prosthetic joint infection].
AB  - Deep sepsis still remains the second most common cause of prosthetic joint
      failure despite its overall incidence is decreasing. It can be defined as a
      bacterial growth and replication on the prosthetic joint surface resulting in
      periprosthetic tissue damage and prosthesis loosening. The implants are colonized
      by airborne-, skin-, tool-, and/ or surgeon-related bacteria during surgery even
      though majority of procedures are performed under strictly respected conditions
      nowadays. After the insertion of the prosthesis into the human body the race
      between bacteria and host cells begins on what will colonize the prosthetic
      surface first. If the bacteria are more successful then they develop on formation
      of biofilm which is the biological correlative for the prosthetic joint infection
      (PJI) resisting effectively against host immune response and antibiotics. That is
      why preventative measures are strongly worth to do it, and removal of the
      prosthesis is the single optimal treatment. Each step in the pathogenesis of
      prosthetic joint infection may represent relevant targets against which
      prevention strategies may be directed. Of them the most useful seems to be
      identification of individual factors predisposing for PJI development, antibiotic
      prophylaxis given before the surgery, and operating room/ surgical quality
      parameters. Key words: prevention, prosthetic joint infection, deep sepsis,
      biofilm, total joint replacement.

PMID- 17026882
TI  - Acute musculoskeletal infection: comparison of different methods for
      intraoperative bacterial identification.
AB  - PURPOSE OF THE STUDY: Various techniques are used for detection of pathogens in
      musculoskeletal infection. These methods differ with respect to reliability and
      ease of handling. A prospective study was performed to evaluate the efficacy of
      three intraoperative techniques. MATERIAL AND METHODS: In 20 cases (18 patients)
      with clinically confirmed acute musculoskeletal infections, intraoperative
      collected swab samples, tissue samples and fluid samples injected into standard
      blood culture vials were used for microbiological diagnosis. Identification of
      bacteria, time necessary for detection and ease of handling during surgery was
      evaluated. RESULTS: In 19 cases bacterial growth was demonstrated using either
      intraoperative swabs or blood culture technique (95% sensitivity), whereas 18
      tissue biopsies were positive (90% sensitivity. 27 bacterial species were
      isolated. In 18 instances for the swab technique, 14 instances for the tissue
      biopsy and 4 operations for the blood culture vials, ease of handling was rated
      as excellent. DISCUSSION: The study demonstrated differences between the three
      tested methods with respect to ease of handling. With respect to the number of
      detected organisms and time for their detection there are no significant
      differences. These last findings are in contrast to of the results of other
      authors. The reason for this could be that during operative dissection an
      accurate and specific collection of specimens from the acute deep infected soft
      tissues and bones independent from the type of surgical procedure is possible.
      Therefore, even with the swab method a high amount of microorganisms can be
      recovered. Especially for intraarticular infections, fluid samples injected into
      standard blood vials is a practical method for the surgeon. In acute
      musculoskeletal infections other than joint infections, there is less benefit for
      the blood culture vials. CONCLUSION: Intraoperative swab technique yields valid
      results comparable to other techniques and is an accurate technique for detection
      of pathogens from acute musculoskeletal infections. Key words: implant,
      infections, bacteriological techniques, comparative study.

PMID- 17026883
TI  - [Method for assessment of distribution of UHMWPE wear particles in periprosthetic
      tissues in total hip arthroplasty].
AB  - PURPOSE OF THE STUDY: Aseptic loosening of implants is the main complication
      affecting the longevity of joint prostheses. The highest proportion of loosening
      occurs due to osteolysis produced by the presence of ultra-high molecular weight
      polyethylene (UHMWPE) wear particles smaller than 1 microm. These can be
      identified by microscopic, spectroscopic or light-scattering methods. Here we
      describe our method for counting wear particles, based on the principle of light
      scattering. MATERIAL AND METHODS: Between 2002 and 2004, we collected samples of
      polyethylene granuloma in 19 patients who underwent revision total hip
      arthroplasty (THA) for aseptic loosening. The samples were obtained from strictly
      defined areas corresponding to the radiographic presentation of periprosthetic
      zones describes by Gruen and DeLee in THA. The frozen samples were lyophilized
      and subjected to delipidation and hydrolyzation procedures in 65 % HNO3. The top
      part of solution containing wear particles was blended with isopropanol, and the
      mixture was filtered through a 10-microm polycarbon membrane. Subsequently, the
      filtrate was filtered through a 0.1-microm membrane. Membranes with trapped
      particles, 0.1 to 1.0 microm in size, were sent for particle characterization and
      quantification. The number of wear particles was measured by the method based on
      light scattering with calibration (LSC), using a Beckman Coulter LS230 analyzer
      that can express particle size distribution in a given volume in percent. The
      method was based on the fact that each particle reflects rays that can be
      measured. The medium measured contained an unknown number of UHMWPE particles and
      a known number of calibration glass beads varying in size. The number of UHMWPE
      particles was calculated from the known number of calibration beads. RESULTS:
      Because the collected samples were also used to develop the method, comprehensive
      data was obtained in six patients only. Particle distribution recorded in the
      periprosthetic zones in THA varied greatly; up to a five-fold difference in
      particle concentration was observed between the zones. In five of the six
      patients, the highest particle concentration was found in zone III. DISCUSSION:
      Seeking a method that would be exact, quick and cheap and would eliminate
      particle aggregation remains the subject of study for researchers cooperating
      with clinical practice. At present methods based on weighing isolated particles
      are used most frequently. We developed the LSC method that, for quantification,
      utilizes the ability of particles to disperse light, and allows us to calculate
      the real numbers of UHMWPE wear particles in a medium containing a known number
      of calibration particles. Although this is an indirect method, it gives more
      accurate results than the direct weighing of particles. The advantages of the LSC
      method involve less demand on sample purity, greater speed and low limits of
      detection. The method is useful for statistical evaluation of a larger number of
      samples. The variation in particle distribution in THA found in this study is in
      agreement with the relevant literature data; it is also in agreement with our
      assumptions and clinical findings. CONCLUSIONS: The authors developed an original
      method for assessment of UHMWPE wear particles in tissue samples, which is
      quicker than the methods so far used. In the periprosthetic tissues studied,
      particles about 1 microm in size were detected; their numbers (about 1010
      particles per gram dry tissue) are in agreement with the literature data. The
      distribution of particles in periprosthetic zones in THA was uneven. The highest
      number of particles was found in the neighboring zone III and zone 7, as
      described by Gruen and DeLee. Key words: wear, polyethylene, total hip
      arthroplasty, light scattering, aseptic loosening, wear particles.

PMID- 17026884
TI  - [Treatment of deep cartilage defects of the knee with autologous chondrocyte
      transplantation on a hyaluronic Acid ester scaffolds (Hyalograft C)].
AB  - PURPOSE OF THE STUDY: The treatment of chondral defects by transplantation of
      autologous chondrocytes has recently shown further development. Various
      biomaterials are used as carriers facilitating attachment and even distribution
      of chondrocytes in the defect. Since 2003 Hyalograft C, hyaluronan-based
      scaffolds, has been used, in a clinical study, for implantation of autologous
      chondrocytes in the treatment of deep chondral lesions of the knee at our
      department. MATERIAL: Eight patients (7 men and 1 woman; average age, 31 years)
      followed up for at least 9 months were evaluated. The lesions with an average
      size of 3.9 cm2 were localized on femoral condyles. METHODS: The outcome of
      surgery was evaluated on the basis of the IKDC Subjective Knee Evaluation Form,
      Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm knee score. The
      patients underwent MR examination preoperatively and at 3, 6 and 12 months after
      surgery. The newly-formed cartilage was assessed by International Cartilage
      Repair Society (ICRS) visual scores at second-look arthroscopy carried out at 9
      to 12 months following transplantation. Consistency of the new cartilage
      developing in the defect and that of healthy cartilage around the defect was
      compared by means of a special indentation probe in three patients. A biopsy
      sample was collected from the grafted site for histological, histochemical and
      immunohistochemical examination. RESULTS: All patients reported improvement in
      knee function on average at 10 months after surgery. The average IKDC subjective
      score increased from 46 points preoperatively to 74 points postoperatively. The
      KOOS evaluation showed pain relief and improved function. In quality of life
      evaluation the average score of 35 points before surgery increased to 70 points
      after it. The average Lysholm knee score was 61 points before and 83 points after
      surgery. MR findings correlated well with arthroscopic findings. Second-look
      arthroscopy showed a normal appearance of the newly-formed cartilage in six, and
      an abnormal appearance in two patients. The average ICRS visual score was 9.4
      points. No graft failure was recorded. The newly-produced tissue had the
      histological characteristics of a mixed hyaline and fibrous cartilage in seven
      patients, and of hyaline-like cartilage in one patient. DISCUSSION: The ICRS
      visual repair assessment of the newly-formed tissue showed that our results were
      better than the one-year outcomes reported by Bartlett et al. (11 patients after
      transplantation of a collagen bilayer seeded with chondrocytes), but worse than
      the results of an Italian multi-center study (55 patients with Hyalograft C-based
      grafts followed up on average for 14 months). At almost one year, implantation of
      on a Hyalograft C resulted in the production of mixed cartilage incorporated well
      in the subchondral bone. Only one patient had mature hyaline cartilage. One year
      is too short to allow for complete remodeling of the newly formed cartilage into
      a mature hyaline cartilage. This is in agreement with other studies suggesting
      that the new cartilage continues to mature and remodel for a time longer than one
      year. CONCLUSIONS: Based on our results we suggest that the use of Hyalograft C
      is a safe and effective option for treatment of deep chondral defects of the
      knee; it is particularly useful in patients in whom the primary defect treatment
      has failed. The application of Haylograft C is relatively quick and easy; this is
      convenient when surgery involves more than one procedure (ligament
      reconstruction, osteotomy). However, a definite evaluation of this method will be
      possible only after long-term results are available. Key words: deep cartilage
      defects, chondral defects, cartilage repair, autologous chondrocyte
      transplantation, hyaluronan- based scaffold, Hyalograft C, cartilage repair
      assessment, ICRS.

PMID- 17026885
TI  - [Complex injuries of the shoulder - floating shoulder].
AB  - Complex injuries of the shoulder are comparatively rare. Within the field of
      complex shoulder injuries this article particularly deals with the diagnosis and
      therapy of the "floating shoulder injury" as a review article. This term
      describes a discontinuation of the osseus and soft tissue suspension of the upper
      extremity from the axial skeleton. By literature review and involvement of recent
      biomechanical studies this article will show the injury patterns that lead to
      instability of the shoulder girdle and the therapeutic to be employed in
      respective cases. Key words: shoulder, floating shoulder, clavicle fracture,
      scapula fracture.

PMID- 17026886
TI  - [Hip joint arthroplasty following surgical treatment of acetabular fracture].
AB  - PURPOSE OF THE STUDY: A group of 49 patients treated by total hip arthroplasty
      after previous surgery for an acetabular fracture are evaluated in this
      retrospective study. MATERIAL: In the period from 1997 to 2004, 49 patients, 35
      men and 14 women, with posttraumatic arthritis following acetabular fracture were
      treated in our department. The average age was 42 years, with 67 % of the
      patients being younger than 40 years. The average follow-up was 42 montsh (range,
      18 to 92). The acetabular fractures evaluated by the AO classification included
      type A1 in 17 patients, type A2 in seven, type B1 in nine, type B2 in six, type
      B3 in seven, type C1 in three and type C2 in two patients. METHODS: In 11
      patients with aseptic necrosis of the femoral head without acetabular deformity,
      cementless Zweymuller Bicon or Spotorno CLS acetabular components were used.
      Twenty-nine patients with acetabular defects of type I and II, according to the
      American Academy of Orthopedic Surgeons (AAOS) classification, underwent
      acetabular reconstruction with the bone impaction grafting technique, using
      allogenic grafts and cementless Zweymuller Bicon acetabular components. Four
      patients with AAOS type III acetabular defects were treated with impacted
      morsellized bone allografts, using titanium mesh and cemented polyethylene
      acetabular cups. Three patients were treated with solid bone grafts fixed with
      osteosynthetic material. In two patients with type IV defects, osteosynthesis
      using a plate completed with allogenic bone graft, a mesh and a cemented cup were
      used. RESULTS: The patients were evaluated with the use of Harris hip scores. In
      20 patients (43 %) the outcomes were excellent, and very good in 18 (37 %),
      satisfactory in six (12 %) and poor in four (8 %) patients. DISCUSSION: Hip joint
      arthroplasty following the surgical treatment of acetabular fracture is indicated
      in patients with post-traumatic hip arthritis. This frequently occurs due to
      complications associated with surgery for acetabular fractures, or the cause
      remains unknown. Some types of these fractures show a high proportion of poor
      results. The group can be divided into two different subgroups: the patients with
      a spherical, healed acetabulum and the patients with acetabular deformity or
      defect, of which the most serious condition is pseudoarthrosis of one or both
      columns. In the first subgroup, the surgical technique of acetabulum replacement
      is the same as in cases with arthritis due to degenerative disease. In the other
      subgroup, the procedure for cup implantation resembles revision arthroplasty for
      acetabular loosening. The options for treating defects or deformities and the
      implants used are identical in both situations. Therefore the results should be
      compared with those of revision arthroplasty and not primary implantation. Scars,
      fibrotic changes in muscles, para-articular ossification, bone defects, residual
      deformities of the acetabulum, devitalized bone fragments or hindering previous
      implants make the surgical procedure more difficult and interfere with good
      results. CONCLUSIONS: Total hip arthroplasty carried out after acetabular
      fracture is technically demanding. The prerequisite for a good result is to
      achieve primary stability of the acetabulum. Acetabular reconstruction is based,
      in the first place, on replacement of the missing bony tissue, and on providing
      conditions for correct alignment of the acetabulum and reliable primary and early
      secondary osteointegration. THA after acetabular fracture achieves poorer results
      than when it is indicated for degenerative disease. Key words: acetabular
      fracture, post-traumatic hip arthritis, total hip replacement.

PMID- 17026887
TI  - [Early primary total hip arthroplasty for acetabular fractures in elderly
      patients].
AB  - PURPOSE OF THE STUDY: The aim of this pilot study was to evaluate the clinical
      and functional outcomes of total hip arthroplasty (THA) in patients with
      acetabular fractures due to a low-energy injury. Acute primary THA included an
      antiprotrusion cage and autologous bone grafting of the acetabulum. This
      prospective study was carried out between 1998 and 2004. MATERIAL: Ten patients,
      of whom six were men, (average age, 71 years; range, 60 to 83 years) with
      acetabular fractures were treated by THA. Two patients had type A2, two had type
      B1, three had type B2 and three had type B3 fractures, as assessed by the AO
      classification. X-ray showed osteoporosis due to decreased bone mass in all
      patients, and dislocations of the fragments in the weight-bearing area of the
      joint exceeded 1 cm. The average follow-up was 36 months. METHODS: Indications
      for primary THA included, in addition to higher age, displacement in the fracture
      line exceeding 1 cm, a fracture line extending to the weight-bearing part of the
      acetabulum, presence of hip arthritis, cartilage injury, defects of the weight
      bearing area of either the femoral head or acetabulum, and Pipkin type IV injury.
      The interval between accident and surgery ranged from 6 to 12 days (average,
      9.5). Three surgical techniques were used, namely, cemented THA with a
      polyethylene cup cemented into an acetabulum-stabilizing cage; reconstruction
      with a cementless RSC acetabular component; internal fixation using screws and a
      cemented cup. Bone grafting of the acetabulum was used in all patients. Evaluated
      were basic operative parameters, complications, X-ray findings, ability to walk
      and Merle d'Aubigne scores. RESULTS: The average operative time was 100 min, the
      average blood loss was 1000 ml. Hip motion showed the following average values:
      flexion, 110 degrees ; extension, 10 degrees ; rotation, 30 degrees -0 degrees 
      30 degrees ; adduction, 25 degrees ; abduction, 35 degrees . All patients
      returned to their preoperative range of motion. X-ray examination showed good
      reduction, bone graft was completely incorporated in the acetabulum, and no
      displacement or signs of loosening or graft migration were recorded. Two patients
      had Brooker type I heterotropic ossification. The final evaluation of function at
      36 months on the basis of the Merle d'Aubigne classification showed excellent and
      good results in four (57 %) and three (43 %) patients, respectively. The
      remaining three patients had a shorter follow-up, but were fully mobile with no
      complications observed. DISCUSSION: It has been reported that bony union of
      acetabular fracture after open reduction and internal fixation (ORIF) was
      achieved in 74 % patients younger than 60 years, but in only 44 % of the patients
      older than 60 years. Secondary THA following ORIF is a demanding technique. Due
      to adhesions and a frequent malposition of the acetabulum, THA is associated with
      and increased risk of infection, tendency to develop para-articular
      ossifications, and a higher risk of early component loosening than in the
      standard procedure. One of the options is to perform acetabular stabilization and
      primary THA at one stage. The results of our study are fully in agreement with
      those reported for THA in hip arthritis or dislocated fracture of the femoral
      neck. CONCLUSIONS: Acute primary THA with the use of a antiprotrusion cage and
      bone grafting for acetabular fractures in elderly patients allows us to employ
      only one surgical technique for definitive repair. It provides primary stability
      and immediate pain relief, permits graded weight-bearing and early pain-free
      mobilization, and may also treat hip arthritis, if it exists. This technique has
      also good prospects for a selected group of younger patients in whom the
      treatment of acetabular fractures has a poor prognosis. Key words: acetabular
      fracture, elderly patient, primary total hip arthroplasty.

PMID- 17026888
TI  - [Cementless ceramic-on-ceramic total hip system].
AB  - PURPOSE OF THE STUDY: This is an experimental and clinical study on the use of
      cementless, ceramic-on-ceramic total hip arthroplasty (THA). MATERIAL AND
      METHODS: In the experimental part, the authors constructed, by means of
      mathematical analysis of finite elements, surface tension standards for the
      ceramic liner at various angles of cup inclination, and identified potentials for
      destruction of the liner. In the clinical trial, they evaluated the outcomes in
      50 patients, out of the 249 implanted prostheses, at five-year follow-up.
      RESULTS: The experiment showed that a slightly steeper inclination the cup
      provided physical conditions for increased longevity of the ceramic liner. In the
      clinical study, no post-operative complications, such as fracture of the
      acetabulum or femur, and dislocation or break of any ceramic part, were recorded.
      No infection or loosening of the prosthesis occurred. The patients did not
      complained of any pain in the hip joint, which is typical of non-cemented THA.
      DISCUSSION: Ceramic-on-ceramic bearing surfaces show the least wear due to high
      biocompatibility. Computer-assisted surgery can markedly reduce the risk of
      incorrect positioning of the acetabular component. In this prospective study, the
      five-year survival of ceramic-on-ceramic THA in 50 patients free from any
      complications, whose Harris hip score was 97.4 points, suggests that objections
      to these prostheses, as raised by some authors, are not justified. CONCLUSIONS:
      In our experience the Plasmacup Bicontact ceramic-on-ceramic prosthesis is one of
      a few options that has a prospect of remaining the only total hip replacement in
      one's lifetime. Key words: total hip replacement, ceramic-on-ceramic.

PMID- 17026889
TI  - [Be careful on the Internet].

PMID- 17026890
TI  - [Bleeding complications after treatment with antithrombotic agents after acute
      coronary syndrome].

PMID- 17026891
TI  - [Survival in cold water. Physiological consequences of accidental immersion in
      cold water].
AB  - This survey addresses the immediate physiological reactions to immersion in cold
      water: cold shock response, diving reflex, cardiac arrhythmias and hypothermia.
      Cold shock response is the initial sympathetic reaction to immersion in cold
      water. The diving reflex is elicited by submersion of the face. Afferent and
      efferent nerves are the trigeminal and vagal nerves. Cardiac arrhythmias occur
      immediately after immersion. If the immersion persists, hypothermia becomes an
      issue. Hypothermia is delayed by habituation to immersion in cold water as well
      as insulating garments, subcutaneous fat and a large lean body mass.

PMID- 17026892
TI  - [Therapeutic hypothermia after perinatal asphyxia--the time is ripe].

PMID- 17026893
TI  - [Bivalirudin: a direct thrombin inhibitor in percutaneous coronary
      interventions].
AB  - Bivalirudin is a direct thrombin inhibitor that has biological and
      pharmacokinetic advantages over heparin, e.g., by inhibiting both fibrin-bound
      and -unbound thrombin. In patients undergoing subacute or elective percutaneous
      coronary intervention, bivalirudin + provisional glycoprotein IIb/IIIa inhibition
      is as effective as unfractionated heparin + glycoprotein IIb/IIIa inhibition and
      is associated with a reduced risk of bleeding. The results of ongoing trials will
      further define the promising role of bivalirudin in the treatment of patients
      with acute coronary syndromes.

PMID- 17026894
TI  - [Bleeding complications after treatment with clopidogrel and acetylsalicylic acid
      after acute coronary syndrome].
AB  - INTRODUCTION: The Clopidogrel in Unstable Angina to Prevent Recurrent Events
      (CURE) study showed that patients with unstable angina pectoris (UAP) and non-ST
      elevation myocardial infarction (NSTEMI) benefit from combined therapy with
      acetylsalicylic acid (ASA) and clopidogrel. However, only patients entering
      clinical randomized trials were studied. We sought to assess whether the risk of
      bleeding increased after the introduction of the CURE criteria in an unselected
      population of Danish patients with NSTEMI or UAP. MATERIALS AND METHODS: The CURE
      criteria were implemented in the Department of Cardiology, Odense University
      Hospital, in December 2001. Two consecutive one-year periods were studied: period
      1, December 2000-November 2001, and period 2, December 2001-November 2002.
      Patient charts were reviewed, and major bleeding complications and the primary
      clinical end point (non-fatal myocardial infarction, stroke or death) was
      registered. Follow-up took place one year later. RESULTS: In all, 290 patients
      were included in period 1 and 189 in period 2. During period 1, there were 12
      (4.1%) and during period 2, 21 (11.1%) major bleeding events (odds ratio 3.07;
      95% CI 1.42-6.65; p = 0.005). Compared with the patients treated with clopidogrel
      and ASA in the CURE study, we also found a three times greater risk of major
      bleeding in period 2. In particular, patients over 70 years of age and patients
      undergoing bypass surgery were at heightened risk. The incidence of the primary
      clinical end point was higher in both period 1 and period 2 than in the CURE
      study. CONCLUSION: Our study demonstrates an increased risk of major bleeding in
      unselected patients receiving combination therapy with ASA and clopidogrel after
      UAP or NSTEMI. Major bleeding complications most frequently occur in patients
      above 70 years of age and following bypass surgery.

PMID- 17026895
TI  - [Peer tutorial programme as a part of the medical curriculum].
AB  - This article shows the possible effects of an integrated intensive introduction
      to medical school using older students as tutors for first-year students. Our
      project resulted in a significant decrease in the average time to completion of
      the first five semesters of the medical bachelor' degree.

PMID- 17026897
TI  - [Patterns of contact with the out-of-hours service and emergency rooms by guest
      workers with immigrant and refugee background in Copenhagen municipality, 1998].
AB  - INTRODUCTION: Outside normal office hours, patients in Denmark with acute
      conditions are treated by the out-of-hours service connected to general practice
      and in the emergency rooms of hospitals. Little is known about the contact
      pattern of immigrants with these services. The purpose of this study was to
      compare the contact rates for immigrants (guest workers and refugees) and non
      immigrants with out-of-hours service and emergency rooms and compare the results
      with the total number of contacts with general practice (out-of-hours service,
      daytime contacts) and emergency rooms. MATERIALS AND METHOD: Data from 2,243,633
      contacts in Copenhagen 1998 registered in the National Patient Registry and
      112,733 visits to emergency units were merged with information about citizenship
      and place of birth in the Central Office of Civil Registration. The contacts were
      described by the average number of contacts per person at risk per year. RESULTS:
      The contact rates with the out-of-hours service were significantly lower for
      immigrant children than for non-immigrants, whereas the number of visits to
      emergency rooms did not show any differences. For both sexes aged 19-59, the
      contact rates for out-of-hours service and emergency rooms were higher for
      immigrants. The total number of contacts was 31-11% lower for children and those
      60+ years of age and 4-20% higher for 19- to 59-year-old immigrants. CONCLUSION:
      Significant differences in the use of acute services by immigrants and non
      immigrants were observed. Whether this is appropriate is questionable.

PMID- 17026896
TI  - [Patterns of contact with general practice in the daytime by guest workers with
      immigrant and refugee background in Copenhagen municipality, 1998].
AB  - INTRODUCTION: Little is known about immigrants' contact with the Danish health
      system. The aim of this study was to compare the pattern of contact with general
      practitioners of guest workers, refugees and non-immigrants in Copenhagen.
      MATERIALS AND METHODS: 2.04 daytime contacts (home visits, clinic consultations
      and telephone consultations) by 423,202 inhabitants during the year 1998 as
      recorded in the National Patient Registry were merged with information about
      citizenship and place of birth in the Danish Central Office of Civil
      Registration. The contacts were described by the average number of contacts per
      person at risk per year. The differences between non-immigrants and immigrants
      were analyzed using Poisson regression. RESULTS: Immigrants and non-immigrants
      showed nearly the same sex- and age-dependent contact pattern. Immigrant children
      (1-18 years) and older people (60+ years) had a lower contact rate than non
      immigrants in the same age groups. The 19- to 59-year-old guest worker women and
      men had 3% and 5% higher contact rates and the refugee women and men 2% and 17%
      higher contact rates, respectively, than non-immigrants in the same age group.
      The percentage of telephone consultations was lower for immigrants and the clinic
      consultation rate higher than for non-immigrants. CONCLUSION: There are sex- and
      age-specific differences between immigrants and non-immigrants. If equity is a
      goal in public health care, we should know more about its actual use. More
      complex research designs are needed, as well as theoretical studies, to shed
      light on these issues.

PMID- 17026898
TI  - [Prolonged survival after accidental immersion in cold water].
AB  - In a recent boat accident, a 25-year-old yachting enthusiast fell overboard and
      survived for 24 hours in 17 degrees C water. Existing survival models are
      discussed in this case report. There is a discrepancy regarding survival
      probability amongst the various models. The calculated survival time for the
      yachtsman ranges from 3 hours to more than 30 hours. A reliable survival-time
      model is needed to determine the appropriate search duration of rescue services.
      In this case, the majority of the models underestimated the actual survival time.

PMID- 17026899
TI  - [Tumor-induced colocolonic invagination in an adult].
AB  - A case of colocolonic invagination is presented. The mass was palpated
      preoperatively and diagnosed by barium enema X-ray and ultrasound. Operation
      confirmed the diagnosis and demonstrated a coecum tumor. The patient was treated
      successfully with a right hemicolectomy.

PMID- 17026900
TI  - [Picture of the month: FLAIR].

PMID- 17026907
TI  - The endovascular explosion: an interview with Dr. Edward B. Diethrich. Interview
      by Roger T. Gregory.
AB  - Dr. Edward B. Diethrich, a pioneer in endovascular surgery, discusses the
      evolution, maturation, and future of endovascular surgery from a personal
      perspective.

PMID- 17026908
TI  - Total laparoscopic aortic surgery versus minimal access techniques: review of
      more than 600 patients.
AB  - In the following paper we describe our experience with a large number of patients
      in which either a laparoscopic assisted procedure or a total laparoscopic
      operation was performed. From 1996 until 2005 a total number of 638 aortic
      patients were operated on using a total laparoscopic or a laparoscopic assisted
      approach. A total laparoscopic operation was accomplished in 236 cases. A
      laparoscopic assisted aortic operation was performed in 402 patients. In aneurysm
      patients a tube graft was more frequently implanted. Thirty-day mortality was
      significantly higher in patients with a total laparoscopic abdominal aortic
      aneurysm repair (3.0%) compared to a laparoscopic assisted procedure (1.8%).
      There was no significant difference in mortality in patients with occlusive
      disease and a total laparoscopic aortofemoral bypass versus a laparoscopically
      assisted operation. The same tendency could be observed when analyzing the
      incidence of major perioperative complications. Again we found no significant
      difference in patients with occlusive disease yet more severe complications
      directly related to the operation in patients with a total laparoscopic aneurysm
      repair. There was a significantly increased complication rate in total
      laparoscopic aortoiliac repair with a bifurcated prosthesis compared to a tube
      graft repair: a tendency we could not observe in aneurysm patients with a
      laparoscopic assisted operation. Our data also show that there is a lot of room
      for technical improvements such as stapling devices or special grafts to reduce
      total operating times as well as the period of aortic crossclamping. The routine
      use of a minilaparotomy can hardly be a solution considering the technical
      drawbacks such as impaired vision and long term complications like ventral
      hernias. Compared to open surgery the midterm results of laparoscopic aortic
      procedures are promising. The time has come to prove that good results can be
      obtained in more than a few specialized centers.

PMID- 17026909
TI  - Statins and biomarkers in claudicants with peripheral arterial disease: cross
      sectional study.
AB  - This exploratory substudy of The Iron (Fe) and Atherosclerosis Study (FeAST)
      compared baseline inflammatory markers, including cytokines, C-reactive protein
      (CRP), and ferritin, in subjects with peripheral arterial disease (PAD) taking
      statins with subjects with PAD who were not taking statins. Inflammatory markers
      in the serum of 47 subjects with PAD not taking statins and a healthy cohort of
      21 medication-free men were compared with 53 PAD subjects taking statins at entry
      to the FeAST. Healthy subjects demonstrated lower levels of tumor necrosis factor
      (TNF)-R1, interleukin-6 (IL-6), and CRP. TNF-alpha R1 averaged 2.28 ng/mL versus
      3.52 ng/mL, p = .0025; IL-6 averaged 4.24 pg/mL versus 16.61 pg/mL, p = .0008;
      and CRP averaged 0.58 mg/dL versus 0.92 mg/dL, p = .0192. A higher level of IL-6
      was observed in PAD statin takers versus PAD subjects not taking statins: 19.47
      pg/mL versus 13.24 pg/mL, p = .0455. As expected, total cholesterol and low
      density lipoprotein levels were lower in the statin-treated group, p = .0006 and
      p = .0001, respectively. No significant differences in inflammatory cytokines
      were detected for varying doses of simvastatin. Additionally, no significant
      differences in inflammatory biomedical markers were found in subjects with PAD
      alone compared with those with concomitant coronary artery disease (CAD).
      Unexpectedly, serum inflammatory cytokine IL-6 levels were significantly higher
      in PAD subjects receiving statins. There was no difference in measured
      inflammatory markers in PAD subjects with concomitant CAD.

PMID- 17026910
TI  - Importance of the arteriographic anatomy of the descending genicular artery and
      sural arteries in patients with atherosclerotic occlusion of the popliteal
      artery.
AB  - Bypasses to the descending genicular artery (DGA) or the medial sural artery
      (MSA) have been performed with acceptable rates of midterm success. The
      arteriographic appearance of the DGA, the MSA, and the lateral sural artery (LSA)
      was described and the applicability of bypass to these vessels was investigated.
      The arteriograms of 45 patients who had occlusion of the below-knee popliteal
      artery were analyzed to determine the presence, dominance, and extension of
      collaterals for each perigeniculate branch, which were used to assess the
      applicability of a perigeniculate bypass. A dominant perigeniculate artery was
      found in 26 arteriograms and corresponded to 13 DGAs, 9 MSAs, and 4 LSAs. Of 14
      applicable perigeniculate bypasses, 2 would be an obligatory bypass and 12 would
      be an alternative to a conventional infrapopliteal bypass. Although rarely an
      obligatory solution, a bypass to a perigeniculate branch artery represents a
      valuable alternative.

PMID- 17026911
TI  - Long-term outcome of operated inflammatory aortic aneurysms.
AB  - Inflammatory aortic aneurysms (IAAs) represent a rare form of aortic aneurysms.
      Compared with atherosclerotic aneurysms, patients with IAA have an increased risk
      of perioperative and long-term morbidity. This retrospective clinical study
      analyzed the outcome after conventional and endovascular repair of IAAs. Patients
      treated for an abdominal IAA between January 1995 and November 2004 were
      included. Imaging (computed tomographic angiography or magnetic resonance
      angiography) was performed preoperatively and at the time of follow-up (mean 2.7
      years). Transperitoneal open repair and endovascular aortic repair were the
      operative procedures used. Over 10 years, 40 patients were treated with
      conventional and 5 patients with endovascular repair. The in-hospital morbidity
      rate was 11.1% (five patients; four conventional, one endovascular). On 10
      patients (47.6%), the retroperitoneal fibrosis was no longer detectable. After
      operative repair, the majority of cases presented with a distinct regression of
      inflammation. Endovascular treatment of IAA represents a feasible alternative
      procedure to open aortic repair.

PMID- 17026912
TI  - Endovascular repair for thoracic aortic disease: tertiary single-center
      experience in northwestern Greece.
AB  - The purpose of this article is to report the initial experience with endovascular
      repair of thoracic aortic disease in a single tertiary vascular unit in
      northwestern Greece. Between 2003 and 2005, 16 patients were treated with
      endovascular techniques for various pathologies of the descending thoracic aorta.
      Twelve patients were treated electively and four emergently. Operative and follow
      up data for a mean time of 18.4 months were retrospectively collected and
      analyzed. Primary technical success was obtained in 14 (87.5%) cases. No early or
      late deaths occurred, and there was no major operation-related complication. No
      paraplegia was observed in our patients. Stent graft-related complications
      occurred in 18.75% (one type 2 and two type 3 endoleaks), but they all had a
      favorable outcome. No further problems have been reported in any of our patients.
      Endovascular stent graft repair for diseases of the thoracic aorta seems to be a
      promising alternative to open surgery, especially for high-risk patients. Long
      term results are needed to confirm the early benefit of this treatment option
      with regard to morbidity and mortality rates. The potential of this technique to
      be applicable even in relatively small, tertiary vascular centers might be of
      great benefit to patients.

PMID- 17026913
TI  - Novel access technique facilitating carotid artery stenting.
AB  - Carotid artery stenting (CAS) may be impossible, or associated with a high risk,
      in patients with severe vessel tortuosity. A novel method of catheterization of
      the carotid artery intended to facilitate CAS is described. It involves the
      placement of a microcatheter and a coronary wire through a dissected superficial
      temporal artery (STA), and then advanced to the ascending aorta. The wire is then
      snared and brought out through a sheath already placed from the common femoral
      artery (CFA). Thus through-and-through access from the STA to the CFA is
      established. The sheath is then brought over the coronary artery into the common
      carotid artery. Using the coronary artery as "buddy wire" the carotid artery
      stenting is carried out in a standard fashion. The potential benefit of this new
      technique is the decrease of risk of the procedures in patients with prohibiting
      vessel tortuosity.

PMID- 17026914
TI  - Endovascular management of blunt abdominal aortic injury.
AB  - The endovascular management of blunt aortic injuries is being used more
      frequently in the trauma patient. Traumatic aortic injuries usually occur in the
      descending thoracic aorta near the origin of the left subclavian artery. Many
      reports in the literature demonstrate the efficacy of endovascular repair of
      blunt thoracic aortic injury. We report here an unusual case of abdominal aortic
      dissection secondary to blunt abdominal trauma following a fall. The patient also
      had associated intra-abdominal injuries requiring bowel resection and repair of
      small bowel mesenteric lacerations. He was treated with a bifurcated abdominal
      endograft with an excellent result after the initial operation was performed to
      treat the bowel injuries.

PMID- 17026915
TI  - Rupture of a popliteal artery aneurysm 10 years after surgical repair.
AB  - The usual method for popliteal artery aneurysm exclusion is distal and proximal
      ligation followed by bypass grafting via a medial approach. This technique
      preserves collaterals to the aneurysm, which might cause back-bleeding and
      symptomatic enlargement. We report the eighth case in the literature of a
      ruptured popliteal artery aneurysm after previous ligation and bypass grafting.
      The ruptured aneurysm was successfully excluded via a posterior approach. The
      advantage of this approach over the medial approach is the possibility of opening
      the aneurysm sac to oversew patent side branches, thereby excluding back
      bleeding. We review the advantages and disadvantages of both the medial and the
      dorsal technique to treat popliteal aneurysms.

PMID- 17026916
TI  - Endovascular exclusion of subclavian artery pseudoaneurysm.
AB  - Subclavian artery pseudoaneurysms are typically a rare occurrence commonly caused
      by iatrogenic injury and trauma. We describe an endovascular approach employing a
      brachiofemoral through-wire technique for the treatment of a left subclavian
      artery pseudoaneurysm in the presence of a hostile aortic arch and great vessel
      anatomy.

PMID- 17026917
TI  - [Photonic revolution or how non linear optics fosters new approaches in cell and
      tissue imaging].

PMID- 17026918
TI  - [Human embryonic stem cells to rescue fulminant hepatic failure].

PMID- 17026920
TI  - [New hopes for cancer immunotherapy].

PMID- 17026919
TI  - [Salmonella transcriptome during macrophage infection].

PMID- 17026921
TI  - [The UN peace-keeping force in the plants: A microRNA, miR164, stabilizes the
      boundary domain in the meristem].

PMID- 17026922
TI  - [Uncoupling between noradrenergic and serotonergic neurons: As a mechanism for
      drug addiction].

PMID- 17026923
TI  - [Functional dissection of a new regulator of DNA replication initiation in
      bacteria].

PMID- 17026924
TI  - [Help yourself and the sky will help you! On the importance of radiative heat
      exchange during nocturnal flight in birds].

PMID- 17026925
TI  - [NEDD1 and microtubule nucleation complexes: To recruit for better organizing].

PMID- 17026926
TI  - [The dog and its genome].

PMID- 17026927
TI  - [A neuropeptide at the origin of testicular aging?].

PMID- 17026928
TI  - [Two sensors to control bacterial life style: the choice between chronic or acute
      infection].

PMID- 17026929
TI  - [Modeling as a tool for analysis in developmental biology].

PMID- 17026930
TI  - [Diversity of plant-pollinator interaction and stability of ecosystems].

PMID- 17026931
TI  - [New approach of fibrosis by multiphoton microscopy with second harmonic
      generation].

PMID- 17026932
TI  - [Bone marrow stem cells to the rescue of Alzheimer's disease].

PMID- 17026933
TI  - [Unexpected properties of red blood cell anion exchanger: The fish lesson].

PMID- 17026934
TI  - [Connexins, renin and hypertension].

PMID- 17026935
TI  - [Nanog and the magic wand].

PMID- 17026937
TI  - [Two-photon laser scanning fluorescence microscopy for functional cellular
      imaging: Advantages and challenges or One photon is good... but two is better!].
AB  - One of the main challenges of modern biochemistry and cell biology is to be able
      to observe molecular dynamics in their functional context, i.e. in live cells in
      situ. Thus, being able to track ongoing molecular events with maximal spatial and
      temporal resolution (within subcellular compartments), while minimizing
      interference with tissue biology, is key to future developments for in situ
      imaging. The recent use of non-linear optics approaches in tissue microscopy,
      made possible in large part by the availability of femtosecond pulse lasers, has
      allowed major advances on this front that would not have been possible with
      conventional linear microscopy techniques. Of these approaches, the one that has
      generated most advances to date is two-photon laser scanning fluorescence
      microscopy. While this approach does not really provide improved resolution over
      linear microscopy in non absorbing media, it allows us to exploit a window of low
      absorbance in live tissue in the near infrared range. The end result is much
      improved tissue penetration, minimizing unwanted excitation outside the focal
      area, which yields an effective improvement in resolution and sensitivity. The
      optical system is also simplified and, more importantly, phototoxicity is
      reduced. These advantages are at the source of the success of two-photon
      microscopy for functional cellular imaging in situ. Yet, we still face further
      challenges, reaching the limits of resolution that conventional optics can offer.
      Here we review some recent advances in optics/photonics approaches that hold
      promises to improve our ability to probe the tissue in finer areas, at faster
      speed, and deeper into the tissue. These include super-resolution techniques,
      introduction of non paraxial optics in microscopy and use of amplified
      femtosecond lasers, yielding enhanced spatial and temporal resolution as well as
      tissue penetration.

PMID- 17026938
TI  - [Second- and third-harmonic generation microscopies for the structural imaging of
      intact tissues].
AB  - One principal advantage of multiphoton excitation microscopy is that it preserves
      its three-dimensional micrometer resolution when imaging inside light-scattering
      samples. For that reason two-photon-excited fluorescence microscopy has become an
      invaluable tool for cellular imaging in intact tissue, with applications in many
      fields of physiology. This success has driven increasing interest in other forms
      of nonlinear microscopy that can provide additional information on cells and
      tissues, such as second- (SHG) and third- (THG) harmonic generation microscopies.
      In recent years, significant progress has been made in understanding the contrast
      mechanisms of these recent methodologies, and high-resolution imaging based on
      intrinsic sources of signal has been demonstrated in cells and tissues. Harmonic
      generation exhibits structural rather than chemical specificity and can be
      obtained from a variety of non-fluorescent samples. SHG is observed specifically
      in dense, non-centrosymmetric arrangements of polarizable molecules, such as
      collagen fibrils, myofilaments, and polarized microtubule bundles. SHG imaging is
      therefore emerging as a novel approach for studying processes such as the
      physiopathological remodelling of the collagen matrix and myofibrillogenesis in
      intact tissue. THG does not require a non-centrosymmetric system ; however no
      signal can be obtained from a homogeneous medium. THG imaging therefore provides
      maps of sub-micrometer heterogeneities (interfaces, inclusions) in unstained
      samples, and can be used as a general purpose structural imaging tool. Recent
      studies showed that this technique can be used to image embryo development in
      small organisms and to characterize the accumulation of large lipid bodies in
      specialized cells. SHG and THG microscopy both rely on femtosecond laser
      technology and are easily combined with two-photon microscopy.

PMID- 17026939
TI  - [Stimulated Raman microscopy (CARS): From principles to applications].
AB  - A new technique in microscopy is now available which permits to image specific
      molecular bonds of chemical species present in cells and tissues. The so called
      Coherent Anti-Stokes Raman Scattering (CARS) approach aims at maximizing the
      light matter interaction between two laser pulses and an intrinsic molecular
      vibrational level. This is possible through a non linear process which gives rise
      to a coherent radiation that is greatly enhanced when the frequency difference
      between the two laser pulses equals the Raman frequency of the aimed molecular
      bond. Similar to confocal microscopy, the technique permits to build an image of
      a molecular density within the sample but doesn't require any labelling or
      staining since the contrast uses the intrinsic vibrational levels present in the
      sample. Images of lipids in membranes and tissues have been reported together
      with their spectral analysis. In the case of very congested media, it is also
      possible to use a non invasive labelling such as deuterium which shifts the
      molecular vibration of the C-H bond down to the C-D bond range which falls in a
      silent region of the cell and tissue vibrational spectra. Such an approach has
      been used to study lipid phase in artificial membranes. Although the technique is
      still under development, CARS has now reach a maturity which will permit to bring
      the technology at a commercial stage in the near future. The last remaining
      bottleneck is the laser system which needs to be simplified but solutions are now
      under evaluation. When combined with others more conventional techniques, CARS
      should give its full potential in imaging unstained samples and like two photons
      techniques has the potential of performing deep tissues imaging.

PMID- 17026940
TI  - [Full-field OCT].
AB  - Optical coherence tomography (OCT) is an emerging technique for imaging of
      biological media with micrometer-scale resolution, whose most significant impact
      concerns ophthalmology. Since its introduction in the early 1990's, OCT has known
      a lot of improvements and sophistications. Full-field OCT is our original
      approach of OCT, based on white-light interference microscopy. Tomographic images
      are obtained by combination of interferometric images recorded in parallel by a
      detector array such as a CCD camera. Whereas conventional OCT produces B-mode
      (axially-oriented) images like ultrasound imaging, full-field OCT acquires
      tomographic images in the en face (transverse) orientation. Full-field OCT is an
      alternative method to conventional OCT to provide ultrahigh resolution images
      (approximately 1 microm), using a simple halogen lamp instead of a complex laser
      based source. Various studies have been carried, demonstrating the performances
      of this technology for three-dimensional imaging of ex vivo specimens. Full-field
      OCT can be used for non-invasive histological studies without sample preparation.
      In vivo imaging is still difficult because of the object motions. A lot of
      efforts are currently devoted to overcome this limitation. Ultra-fast full-field
      OCT was recently demonstrated with unprecedented image acquisition speed, but the
      detection sensitivity has still to be improved. Other research directions include
      the increase of the imaging penetration depth in highly scattering biological
      tissues such as skin, and the exploitation of new contrasts such as optical
      birefringence to provide additional information on the tissue morphology and
      composition.

PMID- 17026941
TI  - [Regulation of p16INK4a, senescence and oncogenesis].
AB  - The transcriptional regulation of p16INK4a is essential for cellular aging and
      oncogenic stress response. This regulation involves p16INK4a transcriptional
      activators such as proteins Ets1 and 2 or E47. The binding of these proteins to
      INK4a promoter can be inhibited by proteins Id-1 or -4 after heterodimer
      formation. The transcriptional inhibition of p16INK4a includes also the
      transcriptional repression by Bmi-1, and an epigenetic regulation which appears
      complex and remains incompletely understood. Actually, INK4a promoter and exon1
      present a CpG island which can be methylated on cytosines by DNA
      methyltransferases. This DNA methylation is preceded by the lysine 9 histone H3
      methylation and by the deacetylation of histone H4 both involved in gene
      silencing. Indeed, RNA Helicase A might protect INK4a against methylation of CpG
      island. Furthermore, chromatin remodelling involving SWI/SNF complex, antagonist
      to Bmi-1, might activate INK4a expression. The analysis of INK4a regulation
      mechanisms and the comprehension of the epigenetic modulation of its expression
      may allow us to develop a rational use of new anti-neoplastic agents.

PMID- 17026942
TI  - [PI3-kinase: Linking immunological synapse to T-cell proliferation].
AB  - T cell clonal expansion contributing to host defense against pathogens is a
      tightly controlled process to maintain the homeostasis of the immune system. Our
      understanding of how T cell growth and proliferation are controlled following
      antigenic stimulation is therefore a major challenge. Antigen recognition occurs
      when a naive T lymphocyte contacts an antigen-presenting cell. A specialized
      junction enriched in T-cell receptors, costimulation molecules and signaling
      adaptors, called the immunological synapse, is then created for several hours
      between the two cell types. Recent discoveries now clarify the molecular
      mechanisms used by this organization to control T cell growth and proliferation.
      It has been established that the immunological synapse functions in fact as an
      integrative platform where class Ia phosphoinositide-3-kinases (PI3Ks) are
      recruited and activated to continuously produce high levels of 3'
      phosphoinositides. These lipids regulate the localization and the activation of a
      wide range of PH-domain containing proteins, among which the serine-threonine
      kinase Akt, a downstream effector of PI3Ks, appears to be a key player. FoxO
      (Forkhead subgroup O) family members control in various cell systems genes
      implicated in apoptosis, stress resistance and cell cycle arrest, thereby
      contributing to maintain quiescence in unstimulated cells. In naive T cells
      contacting antigen-presenting cells a rapid but also very prolonged nuclear
      exclusion of these transcription factors is observed downstream of Akt. Mainly,
      this compartmentalization process is mandatory to induce T cell growth triggered
      by the T cell/antigen-presenting cell interaction. These findings demonstrate
      that to initiate cell cycle progression the formation of the immunological
      synapse is an undemanding tactic used by primary T cells to securely maintain the
      3'-phosphoinositide-dependent mitotic switch governed by the spatial control of
      FoxO transcription factors.

PMID- 17026943
TI  - [Tuberculosis and HIV: The drama of Africa].

PMID- 17026944
TI  - [Differences and similarities of industrial and institutional promotions].
AB  - The Delegation a la Recherche Clinique d'Ile-de-France et de l'Assistance
      Publique/Hopitaux de Paris (AP-HP) has elaborated a pragmatic approach for the
      monitoring of institutionally sponsored clinical studies. The mandatory practices
      aiming at preventing enrolled volunteers from risks and results from fraud and
      poor quality have been reviewed and a four-stage graduate monitoring has been
      defined, which is applied since 2002. This system needs to be scientifically
      assessed and adapted to the permanent evolution of national and international
      regulations. double dagger.

PMID- 17026945
TI  - [Targets of antithrombotic drugs].
AB  - New antithrombotic agents are being developed not only to improve efficacy, but
      also to increase safety in comparison with widely used conventional agents such
      as the oral anticoagulants. New anticoagulant, antiplatelet, and profibrinolytic
      compounds are currently under study in drug development programs, and most of
      those in phase II or III of development are derived from the observation of
      natural phenomena and merely mimic processes developed by mammalians, including
      humans, to avoid thrombosis, or by blood-sucking insects or animals to prevent
      coagulation of the blood their are feeding on. By contrast, drug candidates
      identified by means of rigorous research and designed to target new pathways and
      achieve direct and specific inhibition of factors that are presumed to play an
      important role in thrombogenesis have generally failed to show any benefit and
      sometimes even induce deleterious effects. The clinical development of new drugs,
      even those mimicking natural phenomena, improves our knowledge of the
      pathogenesis of thrombosis and sheds light, retrospectively, on previous
      conceptual errors. The improvement in our basic knowledge and the development of
      new types of drugs suggest that, in contrast to the current antithrombotic
      compounds that are used in a broad range of clinical settings, use of new drugs
      should be restricted to specific situations in which their mechanisms of action
      are predicted to deliver the highest medical benefit. A major obstacle resides in
      the fact that current drug development programs are still required to comply with
      long obsolete guidelines based on the characteristics of first-generation
      antithrombotic agents, and that do not take into account the specific mechanisms
      of action of new drugs. This situation should change, however, and new
      antithrombotic drugs should soon be able to benefit from adapted development
      programs that will make it possible to determine their optimal risk-benefit
      ratio.

PMID- 17026946
TI  - Issues in using state hospital discharge data in injury control research and
      surveillance.
AB  - This study evaluates the quality of injury-related coding in state hospital data
      and their usefulness to injury researchers. Using 1997 hospital discharge records
      from 19 states, hospitalized non-fatal injury-related cases were identified by
      first selecting all cases that met broad criteria for injury, and then dropping
      cases that appeared incorrectly coded as injuries and cases related to medical
      care. Based on our criteria, 1,129,980 non-fatal hospitalized cases were
      identified as probable acute injuries. Three-quarters were coded with a
      traditional injury diagnosis in the primary diagnosis field, and 90% had a
      traditional injury diagnosis somewhere in the first six diagnosis fields. Of
      cases with an injury diagnosis code in the first three diagnosis fields, 88.1%
      were E coded. E coding completeness varied by state, with some states reporting
      high rates of E coding by using non-specific E codes. Other challenges included E
      coded cases where no injury diagnosis was reported and apparent miscoding of the
      E code. We conclude that it is possible to combine multiple states' data if
      researchers are aware of the challenges they may encounter. In order to capture
      all injury-related cases, it is important to scan secondary diagnosis fields.

PMID- 17026947
TI  - Health status of lymphatic filariasis assessed from patients using seven domains
      five levels (7D5L) instrument.
AB  - Health status is the standardized description of health condition of individuals
      either normal or ill due to diseases and is presented as multidimentional
      profiles. In an effort to develop an indicator to assess the impact of morbidity
      intervention against lymphatic filariasis (LF), we assessed the health status of
      seven different clinical manifestations (health states) of LF from the patient's
      perspective. One hundred and seventy-four filarial patients either with hydrocele
      or lymphoedema were involved in the study. Acute episode of adenolymphangitis
      (ADL) among chronic patients was considered as co-morbidity. Severity levels,
      focusing on physical, mental and social dimensions of health were defined and
      quantified, using seven domains and five levels (7D5L) instrument, an extended
      form of EuroQol (5D3L). All the seven domains of health are affected by filarial
      disease, with the levels of severity varying with health states. The mean
      severity score of ADL (25.8) was significantly higher compared to lymphoedema
      (10.7) and hydrocele (6.9) (P<0.05). In males, the mean score of lymphoedema
      (11.6) was significantly higher in comparison to hydrocele (P<0.05). The severity
      scores increase with the progression of filarial disease but independent of
      gender. The health states of LF were further classified based on the percentage
      of severity according to International Classification of Functioning, Disability
      and Health (ICF) on impairments. Lymphoedema grade 4 (oedema with skin changes)
      and ADL were ranked as severe. The importance of these findings is discussed in
      view of priority setting and evaluating the morbidity management under Global
      Programme for Elimination of Lymphatic Filariasis (GPELF).

PMID- 17026948
TI  - Birth weight and neurodevelopmental outcome of children at 2 years of age after
      planned vaginal delivery for breech presentation at term.

PMID- 17026950
TI  - Myth of the ideal cesarean section rate: commentary and historic perspective.

PMID- 17026951
TI  - Histological and biomechanical evaluation of implanted graft materials in a
      rabbit vaginal and abdominal model.
AB  - OBJECTIVE: The objective of the study was to describe the histologic and
      biomechanical changes of implanted dermal collagen graft materials. STUDY DESIGN:
      Twenty rabbits were randomized into 2 groups (6 and 12 weeks, respectively). Each
      rabbit had 4 graft segments (human dermis, porcine dermis, porcine collagen
      coated polypropylene mesh, and autologous fascia) randomly implanted into the
      abdomen and the vagina. Biomechanical testing and histologic analysis was
      performed after recovery of graft segments. RESULTS: Dermal graft segments showed
      a marked decrease in ultimate strength (84% to 86%) and elastic modulus (73% to
      82%) that was significantly different from the decrease seen in autologous fascia
      or coated synthetic mesh (P < .0008 and P < .0001, respectively). The decrease in
      ultimate strength was associated with vaginal implantation (P = .057). Dermal
      graft materials had moderate inflammation and minimal collagen infiltration.
      CONCLUSION: The mechanical properties of dermal graft materials decline after
      implantation. Vaginal implantation may cause a different tissue response to graft
      material than abdominal implantation. Dermal graft material caused moderate
      inflammation and minimal collagen ingrowth remote from implantation.

PMID- 17026953
TI  - Serotonin transporter, tryptophan hydroxylase, and monoamine oxidase A gene
      polymorphisms in premenstrual dysphoric disorder.
AB  - OBJECTIVE: The purpose of this study was to investigate whether common
      polymorphisms of key genes that control the serotonin (5-hydroxytryptamine)
      pathway are associated with premenstrual dysphoric disorder. STUDY DESIGN: The
      study sample comprised 53 women with clinically diagnosed premenstrual dysphoric
      disorder (age range, 27-46 years; mean age, 37.7 years) and 52 healthy control
      subjects (age range, 22-48 years; mean age, 36.2 years). Eight polymorphisms that
      encode the 5-hydroxytryptamine transporter (LPR, VNTR-2, and 3' UTR G/T),
      tryptophan hydroxylase 1 (TPH1 G-6526A, G-5806T, and A218C), and monoamine
      oxidase A (monoamine oxidase A promoter VNTR-1 and exon 8 Fnu 4H1) were
      genotyped. Genotype and allelic frequencies were analyzed by chi-square test and
      stepwise logistic regression analysis. RESULTS: There was no significant
      association between any genotype and clinical category and no significant allelic
      distribution profiles in either the premenstrual dysphoric disorder group or the
      control group. CONCLUSION: These findings do not support a major role for common
      5-hydroxytryptamine transporter, TPH1, and monoamine oxidase A polymorphisms in
      contributing to susceptibility to premenstrual dysphoric disorder.

PMID- 17026954
TI  - [Results of pancreatic cancer surgery].

PMID- 17026956
TI  - Telomerase with mutated catalytic motifs has dominant negative effects on
      telomerase activity and inhibits cell growth.
AB  - Telomerase catalytic subunit (TERT) seems a key factor controlling telomerase
      activity, telomere length, and cell growth. To further address this issue, we
      forced expression of a catalytically inactive mutant human TERT (hTERT) in hTERT
      immortalised sheep fibroblasts to examine its effects. Expression of mutant hTERT
      compromised telomerase activity reconstituted by wild-type hTERT in a manner
      directly attributable to mutant hTERT expression level. High levels of mutant
      hTERT expression inhibited cell growth with a subset of cells entering
      replicative senescence. Furthermore, significant telomere attrition was evident
      in two of three clones with high levels of mutant hTERT expression. Our findings
      are consistent with the notion that hTERT homodimers are necessarily required to
      form a functional telomerase complex at the telomere substrate. We also highlight
      the requirement of a more thorough understanding of telomerase- and telomere
      associated factors to understand fully the interplay that governs telomere
      homeostasis in vitro and in vivo.

PMID- 17026955
TI  - Self-association of isolated large cytoplasmic domain of plasma membrane H+ 
      ATPase from Saccharomyces cerevisiae: role of the phosphorylation domain in a
      general dimeric model for P-ATPases.
AB  - Large cytoplasmic domain (LCD) plasma membrane H+ -ATPase from S. cerevisiae was
      expressed as two fusion polypeptides in E. coli: a DNA sequence coding for Leu353
      Ileu674 (LCDh), comprising both nucleotide (N) and phosphorylation (P) domains,
      and a DNA sequence coding for Leu353-Thr543 (LCDDeltah, lacking the C-terminus of
      P domain), were inserted in expression vectors pDEST-17, yielding the respective
      recombinant plasmids. Overexpressed fusion polypeptides were solubilized with 6 M
      urea and purified on affinity columns, and urea was removed by dialysis. Their
      predicted secondary structure contents were confirmed by CD spectra. In addition,
      both recombinant polypeptides exhibited high-affinity 2',3'-O-(2,4,6
      trinitrophenyl)adenosine-5'-triphosphate (TNP-ATP) binding (Kd = 1.9 microM and
      2.9 microM for LCDh and LCDDeltah, respectively), suggesting that they have
      native-like folding. The gel filtration profile (HPLC) of purified LCDh showed
      two main peaks, with molecular weights of 95 kDa and 39 kDa, compatible with
      dimeric and monomeric forms, respectively. However, a single elution peak was
      observed for purified LCDDeltah, with an estimated molecular weight of 29 kDa, as
      expected for a monomer. Together, these data suggest that LCDh exist in monomer
      dimer equilibrium, and that the C-terminus of P domain is necessary for self
      association. We propose that such association is due to interaction between
      vicinal P domains, which may be of functional relevance for H+ -ATPase in native
      membranes. We discuss a general dimeric model for P-ATPases with interacting P
      domains, based on published crystallography and cryo-electron microscopy
      evidence.

PMID- 17026957
TI  - Analysis of the XBP1 splicing mechanism using endoplasmic reticulum stress
      indicators.
AB  - Under endoplasmic reticulum (ER) stress conditions, XBP1 mRNA is processed by
      unconventional splicing and translated into a functional transcription factor. ER
      stress-specific XBP1 splicing is also known to be activated by IRE1. However,
      many aspects of the molecular mechanism of XBP1 splicing remain to be elucidated.
      We previously developed an indicator system that enabled detection of XBP1
      splicing using fluorescent proteins as the reporter signals. Here, we use a
      modification of this method that employs modified ER stress-indicators and mutant
      IRE1 in vivo and in vitro to analyze XBP1 splicing mechanisms. Our analyses
      suggest that the 506-579 nt region of the XBP1 mRNA is necessary and sufficient
      for XBP1 splicing, that XBP1 splicing can occur in the cytoplasm, and that
      cleavage and ligation of XBP1 mRNA during splicing may occur as a coupled
      reaction.

PMID- 17026958
TI  - p38MAPK mediates benzyl isothiocyanate-induced p21WAF1 expression in vascular
      smooth muscle cells via the regulation of Sp1.
AB  - It has recently been reported that the transcription factors involved in p21WAF1
      activation by certain signaling factors may vary in different cell types.
      However, the role and importance of the signaling pathway in the transcriptional
      regulation of p21WAF1 on vascular smooth muscle cells (VSMC) in response to
      benzyl isothiocyanate (BITC) has been unclear. In this report, we demonstrate
      that BITC induces the p21WAF1 expression at the transcriptional level. This
      increase in p21WAF1 gene expression was due to p38MAPK-dependent activation of
      the p21WAF1 promoter by BITC. Transcription factor Sp1 binding site was
      identified as the cis-element for the activation of p21WAF1 promoter by BITC, as
      determined by deletion and mutation analysis. In addition, gel shift and
      supershift assays demonstrated that this BITC-responsive element binds
      specifically to the transcription factor Sp1. Treatment with SB203580, an
      inhibitor of the p38MAPK, significantly downregulated transactivation of BITC
      induced Sp1. Finally, the transient expression of VSMC with dominant negative
      p38MAPK plasmid suppressed BITC-stimulated Sp1 activity. In conclusion, we report
      that the transcription factor Sp1 involved in the p38MAPK-mediated control of
      p21WAF1 regulation on VSMC in response to BITC has now been identified.

PMID- 17026959
TI  - Association and insulin regulated translocation of hormone-sensitive lipase with
      PTRF.
AB  - Polymerase I and transcript release factor (PTRF) is in human adipocytes mainly
      localized at the plasma membrane. This localization was under control of insulin,
      which translocated PTRF to the cytosol and nucleus, indicating a novel role for
      PTRF in insulin transcriptional control. In the plasma membrane PTRF was
      specifically bound to a triacylglycerol-metabolizing subclass of caveolae
      containing hormone-sensitive lipase (HSL). In response to insulin PTRF was
      translocated to the cytosol in parallel with HSL. PTRF and HSL were
      quantitatively immunoprecipitated from the cytosol by antibodies against either
      PTRF or HSL. The findings indicate also a novel extranuclear function for PTRF in
      the control of lipolysis.

PMID- 17026960
TI  - Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of
      canonical Wnt signaling.
AB  - Placental choriocarcinoma, a reproductive system carcinoma in women, has about
      0.81% occurrence frequency in China, which leads to over 90% lethality due to
      indistinct pathogenesis and the absence of efficient therapeutic treatment. In
      the present study, using immunostaining and reverse transcription PCR, we
      reported that Dickkopf-1 (Dkk-1) is prominently expressed in human
      cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma
      cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and
      carcinogenesis of placental choriocarcinoma. Further, through exogenous
      introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced
      apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1
      in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is
      achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway
      may not have a great role. This discovery is not symphonic to previous functional
      understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data
      indicate the possible correlation between Dkk-1 and human placental
      choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human
      placental choriocarcinomas.

PMID- 17026961
TI  - Hypo-osmotic shock induces nuclear export and proteasome-dependent decrease of
      UBL5.
AB  - The osmolarity of body fluid is strictly controlled through the action of
      diuretic hormones, which are secreted in the hypothalamus. In the mammalian
      brain, ubiquitin-like 5 (UBL5) is expressed in oxytocin- and vasopressin-positive
      neurons in the hypothalamus, and these neurons play a role in regulating
      osmolarity. We examined the dynamics of UBL5 levels in response to hyper- or hypo
      osmotic conditions. Hypo-osmotic conditions led to significantly reduced levels
      of UBL5 both in brain slices from the hypothalamus and in NIH-3T3 cells. This
      decrease in UBL5 was transcription-independent and proteasome-dependent. Time
      course immunocytochemical studies using exogenous UBL5 revealed that the protein
      was exported from the nucleus under hypo-osmotic conditions and decreased in a
      proteasome-dependent manner. This report is the first to describe changes in the
      intracellular and subcellular localization of UBL5 in response to hypo-osmotic
      conditions. Our results imply osmoregulation of UBL5.

PMID- 17026962
TI  - Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal
      cord.
AB  - Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its
      protein were confirmed in rat fetal spinal cord tissues by RT-PCR and
      immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced
      significant proliferation of primary cultured cells from the fetal spinal cord.
      The proliferating cells were then double-stained using antibodies against the
      neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'
      deoxyuridine (BrdU), and the nestin-positive cells were also found to be co
      stained with antibody against GHS-R. Furthermore, binding studies using [125I]des
      acyl ghrelin indicated the presence of a specific binding site for des-acyl
      ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl
      ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin
      induce proliferation of neuronal precursor cells that is both dependent and
      independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are
      involved in neurogenesis of the fetal spinal cord.

PMID- 17026963
TI  - Ethanol augments elevated-[Ca2+]C induced trypsin activation in pancreatic acinar
      zymogen granules.
AB  - It has been long recognized that significant percentage of patients with acute
      pancreatitis often presents with a history of excessive alcohol consumption;
      however, the patho-physiological effect of ethanol on acute pancreatitis remains
      poorly understood. Abnormally elevated cytosolic Ca2+ ([Ca2+]C) has been found to
      be a shared phenomenon in acute pancreatitis that could induce trypsin premature
      activation. Here, we present the effects of ethanol to sensitize zymogen granules
      (ZGs) of pancreas acinar cells to elevated [Ca2+]C leading to zymogen premature
      activation that could result in acute pancreatitis. The pH fluctuations ([pH]G),
      Ca2+ concentration ([Ca2+]G), and premature trypsin activation inside the ZGs
      were monitored directly with specific fluorescence indicators. Our results showed
      that ethanol could act directly on ZGs and cause ZGs more receptive to elevated
      [Ca2+]C that could induce premature activation of zymogen (trypsin). This alcohol
      induced effect is concentration dependent and strongly influenced by the
      surrounding [Ca2+]C. The K+ channels on ZGs membranes are required in the
      sensitization process. Our observations provide a mechanistic understanding of
      the role of ethanol in the initiation phase of alcoholic pancreatitis.

PMID- 17026964
TI  - Mitotic phosphorylation of tankyrase, a PARP that promotes spindle assembly, by
      GSK3.
AB  - The assembly and function of mitotic spindles require poly(ADP-ribosyl)ation of
      spindle components by tankyrase, a poly(ADP-ribose) polymerase that aggregates to
      spindle poles during mitosis. Tankyrase itself is phosphorylated during mitosis,
      but the kinases involved remain undefined. Herein we report that mitotic
      phosphorylation of tankyrase is abrogated in cells treated with the GSK3
      inhibitors LiCl and indirubin. Moreover, the electrophoretic mobility-shift of
      tankyrase arising from mitotic phosphorylation can be reproduced in vitro by GSK3
      mediated phosphorylation. Lastly, mutagenesis study suggested that GSK3 in vitro
      phosphorylates tankyrase on S978, T982, S987, and S991, residues that comprise
      two adjacent copies of the canonical GSK3 phospho-acceptor motif [S/T]-X-X-X
      [S/T]. Collectively, our data suggest that GSK3 contributes to mitotic tankyrase
      phosphorylation, raising the possibility that this phosphorylation might mediate
      some of the established roles of GSK3 in spindle assembly and mitotic
      progression.

PMID- 17026965
TI  - Single-stranded oligonucleotide-mediated gene repair in mammalian cells has a
      mechanism distinct from homologous recombination repair.
AB  - Single-stranded DNA oligonucleotide (SSO)-mediated gene repair has great
      potentials for gene therapy and functional genomic studies. However, its
      underlying mechanism remains unclear. Previous studies from other groups have
      suggested that DNA damage response via the ATM/ATR pathway may be involved in
      this process. In this study, we measured the effect of two ATM/ATR inhibitors
      caffeine and pentoxifylline on the correction efficiency in SSO-mediated gene
      repair. We also checked their effect on double-stranded break (DSB)-induced
      homologous recombination repair (HRR) as a control, which is well known to be
      dependent on the ATM/ATR pathway. We found these inhibitors could completely
      inhibit DSB-induced HRR, but could only partially inhibit SSO-mediated process,
      indicating SSO-mediated gene repair is not dependent on the ATM/ATR pathway.
      Furthermore, we found that thymidine treatment promotes SSO-mediated gene repair,
      but inhibits DSB-induced HRR. Collectively, our results demonstrate that SSO
      mediated and DSB-induced gene repairs have distinct mechanisms.

PMID- 17026966
TI  - Deletion of vitamin E enhances phenotype of Alzheimer disease model mouse.
AB  - Increased oxidative damage is a prominent and early feature in Alzheimer disease
      (AD). However, whether it is a primary cause or merely a downstream consequence
      in AD pathology is still unknown. We previously generated alpha-tocopherol
      transfer protein knockout (Ttpa-/-) mice, in which lipid peroxidation in the
      brain was significantly increased by complete depletion of alpha-tocopherol
      (alpha-Toc). Here we crossed AD transgenic (APPsw) model mice (Tg2576) with Ttpa
      /- mice. The resulting double-mutant (Ttpa-/- APPsw) mice showed earlier and more
      severe cognitive dysfunction in the Morris water maze, novel-object recognition,
      and contextual fear conditioning tests. They also showed increased amyloid beta
      peptide (Abeta) deposits in the brain by immunohistochemical analysis, which was
      ameliorated with alpha-Toc supplementation. In this report we provide clear
      evidence indicating that chronic lipid peroxidation due to alpha-Toc depletion
      enhances AD phenotype in a mouse model.

PMID- 17026967
TI  - Pharmacological profiling of disulfiram using human tumor cell lines and human
      tumor cells from patients.
AB  - The thiocarbamate drug disulfiram has been used for decades in the treatment of
      alcohol abuse. Disulfiram induces apoptosis in a number of tumor cell lines and
      was recently by us proposed to act as a 26S proteasome inhibitor. In this work we
      characterized disulfiram in vitro with regard to tumor-type specificity, possible
      mechanisms of action and drug resistance and cell death in human tumor cell lines
      and in 78 samples of tumor cells from patients using the fluorometric
      microculture cytotoxicity assay and the automated fluorescence-imaging microscope
      ArrayScan((R)). Disulfiram induced cytotoxicity in a biphasic pattern in both
      cell lines and patient tumor cells. Disulfiram induced apoptosis as measured by
      cell membrane permeability, nuclear fragmentation/condensation and caspase-3/7
      activation using high content screening assays. For many of the cell lines tested
      disulfiram was active in sub-micromolar concentrations. When comparing the
      logIC(50) patterns with other cytotoxic agents, disulfiram showed low correlation
      (R<0.5) with all drugs except lactacystin (R=0.69), a known proteasome inhibitor,
      indicating that the two substances may share mechanistic pathways. Disulfiram was
      more active in hematological than in solid tumor samples, but substantial
      activity was observed in carcinomas of the ovary and the breast and in non-small
      cell lung cancer. Disulfiram also displayed higher cytotoxic effect in cells from
      chronic lymphocytic leukemia than in normal lymphocytes (p<0.05), which may
      indicate some tumor selectivity. These results together with large clinical
      experience and relatively mild side effects encourage clinical studies of
      disulfiram as an anti-cancer agent.

PMID- 17026968
TI  - EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion
      injury.
AB  - LPA (lysophosphatidic acid) specific endothelial differentiation gene (EDG)
      receptors have been implicated in various anti-apoptotic pathways. Ischemia of
      the brain and retina causes neuronal apoptosis, which raises the possibility that
      EDG receptors participate in anti-apoptotic signaling in ischemic injury. We
      examined the expression of EDG receptors in a model of retinal ischemia
      reperfusion injury and also tested LXR-1035, a novel analogue of LPA, in the rat
      following global retinal ischemic injury. Rats were subjected to 45 or 60 min of
      raised intraocular pressure. Animals were sacrificed at 24 h post-ischemia and
      retinal tissue was stained for EDG receptors. In separate experiments, animals
      were randomized to receive LXR or saline vehicle by intravitreal injection 24 h
      prior to ischemia. The degree of retinal damage was assessed morphologically by
      measuring the thickness of the inner retinal layers as well as functionally by
      electroretinography (ERG). We found that the normal retina has a baseline
      expression of the LPA receptors, EDG-2 and EDG-4, which are significantly
      upregulated in the inner layers in response to ischemia. Animals pretreated with
      LXR-1035 had dose-dependent, significant reductions in histopathologic damage and
      significant improvement in functional deficits compared with corresponding
      vehicle-controls, after 45 and 60 min of ischemia. These results suggest that LPA
      receptor signaling may play an important role in neuroprotection in retinal
      ischemia-reperfusion injury.

PMID- 17026969
TI  - Aldehyde load in ischemia-reperfusion brain injury: neuroprotection by
      neutralization of reactive aldehydes with phenelzine.
AB  - In ongoing studies of the neuroprotective properties of monoamine oxidase
      inhibitors, we found that phenelzine provided robust neuroprotection in the
      gerbil model of transient forebrain ischemia, with drug administration delayed up
      to 3 h post reperfusion. Since ischemia-reperfusion brain injury is associated
      with large increases in the concentrations of reactive aldehydes in the penumbra
      area, we investigated if the hydrazine function of phenelzine was capable of
      sequestering reactive aldehydes. Both aminoaldehydes and acrolein are generated
      from the metabolism of polyamines to putrescine by polyamine oxidase. These toxic
      aldehydes in turn compromise mitochondrial and lysosomal integrity and initiate
      apoptosis and necrosis. Previous studies have demonstrated that pharmacological
      neutralization of reactive aldehydes via the formation of thioacetal derivatives
      results in significant neuroprotection in ischemia-reperfusion injury, in both
      focal and global ischemia models. In our studies of acrolein and 3-aminopropanal
      toxicity, using an immortalized retinal cell line, we found that aldehyde
      sequestration with phenelzine was neuroprotective. The neuroprotection observed
      with phenelzine is in agreement with previous studies of aldehyde sequestering
      agents in the treatment of ischemia-reperfusion brain injury and supports the
      concept that "aldehyde load" is a major factor in the delayed cell losses of the
      ischemic penumbra.

PMID- 17026970
TI  - Extranuclear estrogen receptor beta immunoreactivity is on doublecortin
      containing cells in the adult and neonatal rat dentate gyrus.
AB  - In adult female rats, estrogen receptor (ER) activation, particularly of ERbeta,
      promotes hippocampal neurogenesis. We previously reported that extranuclear
      ERbeta immunoreactivity (ir) in adult rats is on cellular profiles in or near the
      granule cell layer, which is the location of newly generated cells. During
      development, cells in or near the granule cell layer transiently express high
      levels of estrogen binding and nuclear ERs. Thus, we sought to determine if
      extranuclear ERbeta is in newly generated cells in adult and neonatal rat dentate
      gyrus. Sections from the dentate gyrus of adult proestrus or postnatal day 7 and
      14 female rats were dual-labeled for ERbeta and the new-cell marker doublecortin
      (DCX) and examined by electron microscopy. DCX-containing neurons were found in
      the subgranular hilus in adult rats and were more widespread throughout the
      granule cell layer and hilus of neonatal rats. In both adults and neonatal rats,
      ERbeta immunoreactivity was found in a subset of DCX-labeled neurons. Electron
      microscopic examination of the adult dentate gyrus revealed that most perikarya
      with DCX-ir had the morphological characteristics of granule cells, although a
      few resembled interneurons. Dendrites with DCX-ir also were observed. In both
      adults and neonates, DCX-labeled neuronal perikarya and dendrites contained
      ERbeta-ir; ERbeta-ir usually was aggregated near the plasma membrane,
      mitochondria or endoplasmic reticula. ERbeta-ir was in glial profiles that
      apposed DCX-labeled perikarya and dendrites. These findings are consistent with
      data showing that estrogens can exert non-genomic effects directly and indirectly
      on newly generated cells in neonatal and adult rat dentate gyrus.

PMID- 17026971
TI  - Interaction of interleukin-1beta with muscarinic acetylcholine receptor-mediated
      signaling cascade in cholinergically differentiated SH-SY5Y cells.
AB  - Increased expression of interleukin (IL)-1beta has been found in Alzheimer brain,
      raising the question whether plaque-associated up-regulation of IL-1beta may
      contribute to neurodegeneration. IL-1beta is capable to induce a number of events
      that also occur in Alzheimer's disease such as stimulation of the amyloidogenic
      pathway of amyloid precursor protein processing. However, less is known on
      participation of IL-1beta in specific cholinergic cell loss. To reveal whether IL
      1beta affects muscarinic acetylcholine receptor (mAChR)-mediated intracellular
      signaling, cholinergically differentiated SH-SY5Y cells were exposed to IL-1beta
      for various periods of time followed by stimulation of mAChR with carbachol for 1
      h, and key molecules of cholinergic signaling cascades were determined including
      phosphoinositide hydrolysis, DNA-binding capacity of NFkappaB and AP-1, and
      activity of acetylcholinesterase (AChE). Carbachol stimulation of SH-SY5Y cells
      dose-dependently stimulated the activation of the transcription factors NFkappaB
      and AP-1 as revealed by electrophoretic mobility shift assay (EMSA), while pre
      exposure of SH-SY5Y cells for 24 h with 1 ng/ml IL-1beta completely suppressed
      the carbachol response. mAChR-mediated enhancements of AChE activity by carbachol
      were impaired following pre-exposure of SH-SY5Y cells with IL-1beta, already
      detectable at a concentration of 1 ng/ml and 1 h of exposure time. The data
      indicate that IL-1beta may interfere with the cholinergic signal transduction
      cascade by inhibiting transcription factor activation, thus providing another
      mechanism by which IL-1beta may induce cholinergic dysfunction in Alzheimer's
      disease.

PMID- 17026972
TI  - Why the Brugada syndrome is not yet a disease: syndromes, diseases, and genetic
      causality.

PMID- 17026973
TI  - Simvastatin improves left ventricular function after myocardial infarction in
      hypercholesterolemic rabbits by anti-inflammatory effects.
AB  - OBJECTIVES: Hypercholesterolemia contributes to coronary artery disease
      progression but little is known about its effect on left ventricular (LV)
      function after myocardial infarction (MI). The aim of this study was to
      investigate the effects of hypercholesterolemia and statin treatment in rabbits
      with experimental MI. METHODS AND RESULTS: New Zealand White rabbits on a normal
      or cholesterol-rich diet for 4 weeks, underwent permanent coronary artery
      ligation. Starting on the first day post-MI rabbits were treated with either
      placebo or simvastatin (5 mg/kg/day) for 9 weeks. Hypercholesterolemia itself did
      not affect LV function in sham-operated animals but further impaired LV systolic
      (dP/dtmax -42%) and diastolic (dP/dtmin -47%) function in MI rabbits on placebo.
      Simvastatin treatment not only prevented deterioration of LV function associated
      with hypercholesterolemia but improved LV function (dP/dtmax +130%; dP/dtmin
      +144%, P < 0.05). Simvastatin also attenuated the depression of LV function in
      normocholesterolemic MI rabbits (dP/dtmax +46%; dP/dtmin +53%, P < 0.05).
      Hypercholesterolemia in MI rabbits coincided with a significant increase in C
      reactive protein levels (marker of inflammation) and Rac1-GTPase activity (marker
      of oxidative stress), and a reduction in cardiac sarcoplasmic-reticulum calcium
      ATPase-2 expression and endothelial nitric oxide synthase protein
      phosphorylation, all of which were normalised by simvastatin treatment. Elevated
      serum cholesterol levels were only partially reduced by simvastatin. CONCLUSIONS:
      Hypercholesterolemia further impaired the depressed LV function in rabbits post
      MI. Statin treatment reversed this effect, and conferred additional protection,
      as in normocholesterolemic animals. Our study suggests that anti-inflammatory and
      anti-oxidative effects of simvastatin substantially contribute to its beneficial
      effects on cardiac function after MI.

PMID- 17026974
TI  - Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in
      patient management.
AB  - Drugs are bound to various serum proteins in different degrees and only unbound
      or free drug is pharmacologically active. Although free drug concentration can be
      estimated from total concentration, for strongly bound drugs, prediction of free
      level is not always possible. Conditions like uremia, liver disease and
      hypoalbuminemia can lead to significant increases in free drug resulting in drug
      toxicity even if the concentration of total drug is within therapeutic range.
      Drug-drug interactions may also lead to a disproportionate increase in free drug
      concentrations. Elderly patients may have increased free drug concentrations due
      to hypoalbuminemia. Elevated free phenytoin concentrations have also been
      reported in patients with AIDS and pregnancy. Currently free drug concentrations
      of anticonvulsants such as phenytoin, carbamazepine and valproic acid are widely
      measured in clinical laboratories. Newer drugs such as mycophenolic acid mofetil
      and certain protease inhibitors are also considered as candidates for monitoring
      free drug concentration.

PMID- 17026975
TI  - Brain natriuretic peptide limits myocardial infarct size dependent of nitric
      oxide synthase in rats.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) has recently been shown to have a
      cardioprotective effect in animal models of myocardial ischemia-reperfusion (I-R)
      injury. We hypothesized that exogenous BNP limits myocardial infarction on nitric
      oxide synthase pathway. METHODS: A rat model of myocardial I-R injury was
      established by ligating the left descending coronary artery for 30 min and then
      reperfusing for 2 h. BNP was injected with different dose 5 min after the
      ligation and lasting for 145 min. The myocardial infarct size and the area at
      risk of ischemia were measured by staining with triphenyltetrazolium chloride
      (TTC) and Evans blue dye. To examine the role of nitric oxide synthase (NOS),
      expression of eNOS in the left ventricle was analyzed by western blotting. Nomega
      nitro-L-arginine methyl ester (L-NAME; 30 ug/kg), or S-methylisothiourea (SMT; 3
      ug/kg) was administrated before I-R with or without BNP. RESULTS: The control
      infarct-to-risk ratio was 45.1+/-1.72% (means+/-SE). BNP infused 5 min after
      ischemia limited infarct size in a dosage-dependent manner, with maximal
      protection observed at 0.01 ug/(kg min) (infarct-to-risk: 24.7+/-1.69%, P<0.01
      vs. control), associated with a 10-fold increase of myocardial endothelial nitric
      oxide synthase above the control value. Protection afforded by BNP was abolished
      by L-NAME but not by SMT, suggesting the involvement of putative endothelial but
      not inducible nitric oxide synthase activation. CONCLUSIONS: We conclude that
      natriuretic peptide/NOS/NO signaling may constitute an important injury-limiting
      mechanism in myocardium.

PMID- 17026976
TI  - Learning about occlusion: initial assumptions and rapid adjustments.
AB  - We examined 6-month-olds abilities to represent occluded objects, using a corneal
      reflection eye-tracking technique. Experiment 1 compared infants' ability to
      extrapolate the current pre-occlusion trajectory with their ability to base
      predictions on recent experiences of novel object motions. In the first condition
      infants performed at asymptote ( approximately 2/3 accurate predictions) from the
      first occlusion passage. In the second condition all infants initially failed to
      make accurate prediction. Performance, however, reached asymptote after two
      occlusion passages. This is the first study that demonstrates such rapid learning
      effects during an occlusion task. Experiment 2 replicates these effects and
      demonstrates a robust memory effect extending 24h. In occlusion tasks such long
      term memory effects have previously only been observed in 14-month-olds (Moore &
      Meltzoff, 2004).

PMID- 17026977
TI  - Apes know that hidden objects can affect the orientation of other objects.
AB  - Four bonobos, seven gorillas, and six orangutans were presented with two small
      rectangular boards on a platform. One of the boards had a piece of food under it
      so that it acquired an inclined orientation whereas the other remained flat on
      the platform. Subjects preferentially selected the inclined board. In another
      experiment, subjects were initially presented with two inclined boards and a
      transformation took place in which one of the boards fell flat to the platform
      while the other remained inclined. Subjects also preferred the board that
      remained inclined. Two additional experiments highlighted some of the possible
      limitations of their reasoning in this task. Presented with two inclined boards,
      one of which was visibly supported by a piece of wood, they failed to
      systematically select the unsupported one whose only reason for being inclined
      was the presence of the reward. Another experiment presented two rewards in each
      trial (instead of the customary one) in one of the following two combinations:
      large banana vs. small carrot or small banana vs. large carrot. Prior to the
      test, E presented both rewards to the subject and then hid each of them under one
      of the boards so that both boards were differentially inclined due to the
      different sizes of the rewards involved. Although subjects selected the board
      that showed a greater inclination (thus securing the larger reward), they
      disregarded the type of food that was involved. This often meant that they chose
      the large carrot over the small banana even though they reversed such a choice
      when the rewards were not occluded by the boards. Providing subjects with a
      'reminder' of the type of reward hidden under the boards did not alter the
      original results. There was no evidence of learning throughout the various
      experiments and control tests ruled out the possibility of inadvertent cuing by
      the experimenter, poor performance due to a lack of motivation, or good
      performance due to a predisposition to select objects with sloped surfaces. It is
      concluded that subjects made some inferences about the reason for the inclined
      orientation of the boards, and not simply associated an inclined orientation with
      the presence of the reward.

PMID- 17026978
TI  - Long-term signal detection, segmentation and summarization using wavelets and
      fractal dimension: a bioacoustics application in gastrointestinal-motility
      monitoring.
AB  - The current paper describes a wavelet-based method for long-term processing and
      analysis of gastrointestinal sounds (GIS). Windowing techniques are used to
      select sequential blocks of the prolonged multi-channel recordings and proceed to
      various wavelet-domain processing stages. De-noising, significant-activity
      detection, automated segmentation and extraction of summary curves are applied in
      an integrated mode, allowing for enhanced content manipulation and analysis. The
      proposed analysis scheme combines flexible long-term graphical representation
      tools, while maintaining the ability of quick browsing via visualization and
      auralization of the detected short-term events. This work is part of a project
      aiming to implement non-invasive diagnosis over gastrointestinal-motility (GIM)
      physiology. However, the proposed techniques might be applied to any study of
      long-term bioacoustics time series.

PMID- 17026979
TI  - Beneficial effect of intracellular free high-mannose oligosaccharides on
      cryopreservation of mammalian cells and proteins.
AB  - The cryoprotective effect of intracellular free high-mannose oligosaccharides
      (HMOS) on mammalian cells and proteins was examined by monitoring PC-12 cell
      viability and assaying protein kinase C (PKC)-epsilon activity. 1
      Deoxymannojirimycin, an inhibitor of alpha-mannosidase, to cause an increase in
      intracellular free HMOS, significantly rescued PC-12 cells with 2-h freezing
      insult at -15 degrees C in a concentration (1-50mM)- and pretreatment time (48
      72h)-dependent manner, as compared with unpretreated cells; full rescue from
      freezing injury was obtained with 1-deoxymannojirimycin at more than 25mM for 48
      h pretreatment and more than 3mM for 72- and 96-h pretreatment. For PC-12 cells
      pretreated with 1-deoxymannojirimycin at 1mM for 72h, thawed cell viability after
      more than 8-w cryopreservation at -80 degrees C in 10% (v/v) dimethyl sulfoxide
      was much higher than that for cells without pretreatment. PKC-epsilon activity
      was well preserved after 16-h cryopreservation at -20 degrees C in the presence
      of mannose 9-N-acetylglucosamine 2 (Man9-GlcNAc2) (1 mM), an HMOS, while the
      activity was reduced to 15% without Man9-GlcNAc2. Collectively, the results of
      the present study suggest that intracellular free HMOS is a key molecule to
      protect mammalian cells and proteins from freezing injury; in other words, HMOS
      could be a new target for cryopreservation of mammalian cells and proteins.

PMID- 17026980
TI  - Mechanisms of gonadal morphogenesis are not conserved between chick and mouse.
AB  - To understand mechanisms of sex determination, it is important to know the
      lineage relationships of cells comprising the gonads. For example, in mice, the Y
      linked gene Sry triggers differentiation of Sertoli cells from a cell population
      originating in the coelomic epithelium overlying the nascent gonad that also
      gives rise to uncharacterised interstitial cells. In contrast, little is known
      about origins of somatic cell types in the chick testis, where there is no Sry
      gene and sex determination depends on a ZZ male/ZW female mechanism. To
      investigate this, we performed fate mapping experiments in ovo, labelling at
      indifferent stages the coelomic epithelium by electroporation with a lacZ
      reporter gene and the underlying nephrogenous (or mesonephric) mesenchyme with
      chemical dyes. After sex differentiation, LacZ-positive cells were exclusively
      outside testis cords and were 3betaHSD-negative, indicating that the coelomic
      epithelium contributes only to non-steroidogenic interstitial cells. However, we
      detected dye-labelled cells both inside and outside the cords. The former were
      AMH-positive while some of the latter were 3betaHSD-positive, showing that
      nephrogenous mesenchyme contributes to both Sertoli cells and steroidogenic
      cells. This is the first demonstration via lineage analysis that steroidogenic
      cells originate from nephrogenous mesenchyme, but the revelation that Sertoli
      cells have different origins between chick and mouse suggests that, during
      evolution, mechanisms of gonad morphogenesis may diverge alongside those of sex
      determination.

PMID- 17026981
TI  - Fgf signaling negatively regulates Nodal-dependent endoderm induction in
      zebrafish.
AB  - In zebrafish development, Nodal signaling is critical for the induction of
      endoderm and mesoderm. Three transcription factors downstream of Nodal, Bonnie
      and Clyde (Bon), Faust (Fau)/Gata5 and Casanova (Cas), are required for endoderm
      induction. However, it is not yet fully understood how the Nodal signaling
      pathway regulates the decision process of endoderm and mesoderm induction. In
      this study, we focused on Fgf signaling, downstream of Nodal signaling, during
      endoderm induction. We found that activation of Fgf signaling decreases the
      number of cas-expressing endodermal cells. Conversely, inhibition of this
      signaling increases the number of endodermal cells without affecting the
      expression of Nodal, Nodal antagonists, bon or fau/gata5. Inhibition of Fgf
      signaling in endoderm mutants suggests that this signaling negatively regulates
      cas expression by a pathway parallel to Bon and Fau/Gata5 in the molecular
      cascade leading to endoderm. Furthermore, activation of Fgf signaling can
      overcome Cas-mediated abrogation of mesodermal gene expression. Altogether, these
      results suggest that Fgf signaling negatively regulates endoderm induction,
      possibly through repression of cas expression and down-regulation of Cas
      function.

PMID- 17026982
TI  - VCAM-1 inhibits TGFbeta stimulated epithelial-mesenchymal transformation by
      modulating Rho activity and stabilizing intercellular adhesion in epicardial
      mesothelial cells.
AB  - Regulation of epithelial-mesenchymal transformation (EMT) is of central
      importance both in normal development and in disease. During heart development,
      cells of the superficial epicardial mesothelium undergo EMT to give rise to
      precursor cells of the coronary vasculature and cardiac fibroblasts. Here we
      report that the alpha(4)beta(1) integrin ligand, VCAM-1, inhibits EMT of chick
      epicardial mesothelial cells stimulated by TGFbeta isoforms. We further
      investigated the molecular basis of this inhibition using cultured chick
      embryonic and rat adult epicardial mesothelial cells. We observed that VCAM-1
      increased cortical actin filaments at intercellular junctions and reduced stress
      fibers across epicardial cells. VCAM-1 inhibited stress fiber formation by
      TGFbeta1, TGFbeta2, TGFbeta3 and lysophosphatidic acid and altered Rho activity
      stimulated by TGFbeta3. This was accompanied by an increase in tyrosine
      phosphorylation of p190RhoGAP. All three TGFbeta isoforms weakened intercellular
      adhesion, reduced membrane localization of beta-catenin and E-cadherin and
      stimulated epicardial EMT in chick hearts. Each of these effects was restricted
      by simultaneous VCAM-1 treatment. Our data support the hypothesis that VCAM-1 can
      alter epicardial EMT at two key points: it limits Rho-dependent events such as
      stress fiber formation and it maintains the association of beta-catenin and E
      cadherin with the adherens junction.

PMID- 17026983
TI  - Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse
      hindbrain.
AB  - Sonic Hedgehog (Shh) signaling plays a critical role during dorsoventral (DV)
      patterning of the developing neural tube by modulating the expression of neural
      patterning genes. Overlapping activator functions of Gli2 and Gli3 have been
      shown to be required for motoneuron development and correct neural patterning in
      the ventral spinal cord. However, the role of Gli2 and Gli3 in ventral hindbrain
      development is unclear. In this paper, we have examined DV patterning of the
      hindbrain of Shh(-/-), Gli2(-/-) and Gli3(-/-) embryos, and found that the
      respective role of Gli2 and Gli3 is not only different between the hindbrain and
      spinal cord, but also at distinct rostrocaudal levels of the hindbrain.
      Remarkably, the anterior hindbrain of Gli2(-/-) embryos displays ventral
      patterning defects as severe as those observed in Shh(-/-) embryos suggesting
      that, unlike in the spinal cord and posterior hindbrain, Gli3 cannot compensate
      for the loss of Gli2 activator function in Shh-dependent ventral patterning of
      the anterior hindbrain. Loss of Gli3 also results in a distinct patterning defect
      in the anterior hindbrain, including dorsal expansion of Nkx6.1 expression.
      Furthermore, we demonstrate that ventral patterning of rhombomere 4 is less
      affected by loss of Gli2 function revealing a different requirement for Gli
      proteins in this rhombomere. Taken together, these observations indicate that
      Gli2 and Gli3 perform rhombomere-specific function during DV patterning of the
      hindbrain.

PMID- 17026984
TI  - The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N
      at micromolar concentrations: off-target alterations of signaling mediated by the
      bradykinin B1 and angiotensin receptors.
AB  - The N-terminal sequence of icatibant, a widely used peptide antagonist of the
      bradykinin B(2) receptors, is analogous to that of other known aminopeptidase N
      inhibitors. Icatibant competitively inhibited the hydrolysis of L-Ala-p
      nitroanilide by recombinant aminopeptidase N (K(i) 9.1 microM). In the rabbit
      aorta, icatibant (10-30 microM) potentiated angiotensin III, but not angiotensin
      II (contraction mediated by angiotensin AT(1) receptors), and Lys-des-Arg(9)
      bradykinin, but not des-Arg(9)-bradykinin (effects mediated by the bradykinin
      B(1) receptors), consistent with the known susceptibility of these agonists to
      aminopeptidase N. At concentrations possibly reached in vivo (e.g., in kidneys),
      icatibant alters physiological systems different from bradykinin B(2) receptors.

PMID- 17026986
TI  - N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell
      apoptosis and restores eNOS expression.
AB  - The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is
      increased in pathological conditions, such as diabetes, which initiate or
      exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive
      oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha
      induced endothelial cell apoptosis. We investigated the effects of the
      antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular
      endothelial cell (cell line ECV304) apoptosis, NO production and lipid
      peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated
      (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the
      presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h.
      Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow
      cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with
      increased inducible NO synthase but reduced endothelial NO synthase (eNOS)
      protein expression. NO production and the levels of the lipid peroxidation
      product malondialdehyde were concomitantly increased. Treatment with NAC at 30
      mmol/l restored eNOS expression and further increased NO production as compared
      to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis.
      This was accompanied by increased superoxide dismutase activity, increased
      glutathione peroxidase production and reduced malondialdehyde levels. N
      acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF
      alpha-induced endothelial cell apoptosis and cell viability despite it slightly
      enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF
      alpha-induced human vascular endothelial cell apoptosis is associated with the
      restoration of eNOS expression.

PMID- 17026985
TI  - p38 mitogen-activated protein kinase inhibitor SB203580 reverses the
      antianalgesia induced by dextro-morphine or morphine in the mouse spinal cord.
AB  - We have previously demonstrated that intrathecal pretreatment with dextro
      morphine or morphine attenuates the morphine-produced antinociception. The
      phenomenon has been defined as antianalgesia, which is mediated by a non-opioid
      receptor [Wu, H., Thompson, J., Sun, H., Terashvili, M., Tseng, L.F., 2005.
      Antianalgesia: stereo-selective action of dextro-morphine over levo-morphine on
      glia in the mouse spinal cord. J. Pharmacol. Exp. Ther. 314, 1101-1108]. To
      determine if p38 mitogen-activated protein kinase (MAPK) is involved in the
      antianalgesia, the effects of p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) on the attenuation of
      the morphine-produced tail-flick inhibition induced by dextro-morphine or
      morphine were studied in male CD-1 mice. Intrathecal pretreatment with SB203580
      (24.2 nmol) reversed the attenuation of the morphine-produced tail-flick
      inhibition induced by dextro-morphine (33 fmol) or morphine (0.3 nmol)
      pretreatment. The finding indicates that the antianalgesia induced by dextro
      morphine or morphine is mediated by the activation of p38 MAPK in the mouse
      spinal cord.

PMID- 17026987
TI  - Specific down-regulation of spinal mu-opioid receptor and reduced analgesic
      effects of morphine in mice with postherpetic pain.
AB  - The analgesic effects of opioid agonists and the expression of mu- and kappa
      opioid receptors were compared between mice with herpetic pain and those with
      postherpetic pain induced by herpetic virus inoculation. Morphine inhibited
      herpetic pain more effectively than postherpetic pain. Intrathecal injection
      reduced the analgesic effects of morphine on postherpetic pain, but
      intracerebroventricular injection did not. The kappa-opioid receptor agonist
      nalfurafine suppressed herpetic and postherpetic pain to similar degrees. mu
      Opioid receptor-like immunoreactivities in the lumbar dorsal horn were markedly
      decreased at the postherpetic, but not herpetic, stage of pain. In the dorsal
      root ganglia, the expression of mu-opioid receptor mRNA was significantly
      decreased in mice with postherpetic pain, whereas the kappa-opioid receptor mRNA
      level was not altered. These results suggest that specific down-regulation of the
      mu-opioid receptor in the primary sensory neurons is responsible for the reduced
      analgesic action of morphine on postherpetic pain. The kappa-opioid receptor may
      be a useful target for the analgesic treatment of postherpetic neuralgia.

PMID- 17026988
TI  - Anti-hyperlipidemic properties of CM108 (a flavone derivative) in vitro and in
      vivo.
AB  - Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha
      are ligand-activated transcription factors that belong to nuclear receptors
      superfamily and are involved in the regulation of lipid metabolism. PPAR,
      especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists
      can regulate the expression or biosynthesis of some factors involved in the
      formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding
      cassette transporter A1 (ABCA1). It is well known that HDL plays an important
      role in the treatment of hyperlipidemia as the carrier of reverse cholesterol
      transport. In the present study, the anti-hyperlipidemic properties of CM108, a
      derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa
      2lambda(5)-phospha-cyclopenta[b]naphthalen-8-one, were studied. Through the
      transactivation assays of in vitro study, it was discovered that CM108 could
      activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml,
      which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and
      apoA-II production, whereas reducing apoC-III production significantly.
      Furthermore, after in vivo study that the hyperlipidemic rats were treated with
      CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels
      (26.7%, P<0.05) and a significant decrease was also noticed in triglyceride
      levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control
      animals. Meanwhile, the atherogenicity index, represented by total
      cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108
      can effectively elevate HDL levels and lower triglyceride levels in
      hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins
      related to HDL.

PMID- 17026989
TI  - Roles of stretch-activated cation channel and Rho-kinase in the spontaneous
      contraction of airway smooth muscle.
AB  - In guinea pigs, it is well-known that mechanical stretch of airway smooth muscle
      exhibits spontaneous tone which is mediated by cyclooxygenase (COX) activation.
      We tested the hypothesis that this spontaneous contraction of airway smooth
      muscle is mediated by stretch-activated non-selective cation channels and the
      Rho/Rho-kinase pathway, as well as COX-2 using a pharmacological approach.
      Isometric force and intracellular Ca(2+) concentrations ([Ca(2+)](i)) were
      assessed in isolated guinea pig tracheal smooth muscle tissues. The samples were
      stretched to a given level and the muscle behavior was monitored under isometric
      conditions. We observed an increase in [Ca(2+)](i) and subsequent force
      generation over a 15-min period. The augmented [Ca(2+)](i) and spontaneous
      contraction due to the stretch were markedly attenuated by application of Gd(3+),
      an inhibitor of stretch-activated channels, and removal of extracellular Ca(2+).
      In contrast, nifedipine only had a mild inhibitory effect on the contraction. (R)
      (+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide (Y-27632; a Rho
      kinase inhibitor) abolished the spontaneous contraction with no changes in
      [Ca(2+)](i). Simvastatin, which down-regulates Rho activity, also significantly
      inhibited the contraction. Moreover, indomethacin, an inhibitor of COX-1 and -2,
      and N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398; a COX-2
      inhibitor) abolished the stretch-induced contraction without affecting
      [Ca(2+)](i), whereas the inhibitory effect of 5-(4-chlorophenyl)-1-(4
      methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC560; a COX-1 inhibitor) on the
      contraction was much less. These findings demonstrated that Ca(2+) entry via
      stretch-activated channels, the Rho/Rho-kinase pathway, and COX-2 are involved in
      the mechanotransduction in guinea pig tracheal smooth muscle. Additionally, while
      the Rho/Rho-kinase pathway and COX-2 regulate the spontaneous contraction
      independently of [Ca(2+)](i), COX-1 is not involved in the stretch-induced force
      generation.

PMID- 17026990
TI  - Piceatannol stimulates osteoblast differentiation that may be mediated by
      increased bone morphogenetic protein-2 production.
AB  - Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a polyphenol present in
      grapes and wine. By means of alkaline phosphatase activity and osteocalcin enzyme
      linked immunosorbent assay (ELISA), we have shown that piceatannol exhibits a
      significant induction of differentiation in immortalized fetal osteoblasts
      (hFOB), and osteosarcoma cells (MG-63). Alkaline phosphatase and osteocalcin are
      phenotypic markers for early-stage differentiated osteoblasts and terminally
      differentiated osteoblasts, respectively, our results indicate that piceatannol
      stimulate osteoblast differentiation at various stages (from maturation to
      terminally differentiated osteoblasts). Induction of differentiation by
      piceatannol was associated with increased bone morphogenetic protein-2 (BMP-2)
      production. Addition of purified BMP-2 protein did not increase the upregulation
      of alkaline phosphatase activity and osteocalcin secretion by piceatannol,
      whereas the BMP-2 antagonist noggin blocked piceatannol and BMP-2-mediated
      alkaline phosphatase activity, and osteocalcin secretion enhancement, indicating
      that BMP-2 production is required in piceatannol-mediated osteoblast maturation
      and differentiation. In conclusion, piceatannol increased BMP-2 synthesis, and
      this effect may contribute to its action on the induction of osteoblasts
      maturation and differentiation, followed by an increase of bone mass. Decreases
      in new bone formation, followed by estrogen deficiency or various pathologic
      factors, may contribute to the mechanisms involved in postmenopausal
      osteoporosis.

PMID- 17026991
TI  - mGlu5 receptors are involved in the discriminative stimulus effects of self
      administered ethanol in rats.
AB  - Recent work has identified a role for metabotropic glutamate receptor subtype 5
      (mGlu(5)) in the discriminative stimulus properties of investigator-administered
      ethanol. The purpose of this study was to determine if mGlu(5) receptors modulate
      the discriminative stimulus properties of self-administered ethanol. Results show
      that the mGlu(5) receptor antagonist 6-Methyl-2-(phenylethynyl)pyridine (MPEP; 10
      mg/kg) inhibited the discriminative stimulus properties of consumed ethanol
      during a self-administration test session. Further, 10 mg/kg MPEP increased and 1
      mg/kg MPEP decreased the amount of self-administered ethanol required to produce
      full substitution. These results indicate that mGlu(5) receptors are involved in
      the expression of the discriminative stimulus properties of self-administered
      ethanol.

PMID- 17026992
TI  - N-tosyl-L-phenylalanyl-chloromethyl ketone reduces ceramide during hypoxic
      ischemic brain injury in newborn rat.
AB  - N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) suppresses apoptosis and
      protects neurons from damage in animal models. TPCK is thought to act by
      inhibiting ceramide production by sphingomyelinase. Ceramide is a proapoptotic
      intracellular signal that is involved in the cerebral ischemia. We wished to see
      whether ceramide contributes to TPCK's neuroprotective effects in vivo. Seven-day
      old rat pups had the right carotid arteries permanently ligated followed by 2.5 h
      of hypoxia (8% oxygen). TPCK (10 mg/kg, n=62) or vehicle (n=63) was administered
      by i.p. 5 min prior to hypoxia. The level of ceramide in brain cortex both in
      lesioned and unlesioned hemispheres was measured at 8 h, 18 h, 24 h, 2 and 5 days
      after hypoxia-ischemia using reversed phase high performance liquid
      chromatography. The level of ceramide significantly increased due to hypoxic
      ischemia at 18, 24 h and 2 days after hypoxia (P<0.05 or P<0.01) but not at 8 h
      or 5 days after hypoxia as compared to the contralateral hemisphere or a sham
      group. Pretreatment with TPCK reduced this increase. We also examined the level
      of sphingomyelin and the activities of the ceramide synthesizing sphingomyelinase
      enzymes by thin layer chromatography. The activities of acidic and neutral
      sphingomyelinase significantly increased due to hypoxic ischemia at 24 h after
      hypoxia. TPCK significantly reduced this increase (P<0.05 vs. vehicle) but did
      not affect the level of sphingomyelin. The results are consistent with the
      hypothesis that ceramide is involved in TPCK's neuroprotective effects in hypoxic
      ischemic brain injury in the newborn rat.

PMID- 17026993
TI  - Dexfenfluramine does not worsen but moderates progression of chronic hypoxia
      induced pulmonary hypertension.
AB  - This study shows for the first time, that dexfenfluramine, a 5-HT(2) receptor
      agonist, attenuates the development of chronic hypoxia-induced pulmonary
      hypertension. Chronic exposure to hypoxia, 4 weeks, induced hypoxic pulmonary
      hypertension in adult rat as haemodynamic and cardiac measurements showed
      significant modifications in right ventricle parameters (free wall right
      ventricle thickness; pulmonary acceleration time and velocity time integral) in
      chronic hypoxic control when compared to normoxic control animals. We observed
      that free wall right ventricle thickness and pulmonary velocity time integral
      were significantly less in chronic hypoxic rats treated with dexfenfluramine when
      compared to chronic hypoxic control rats. Similarly, rats exposed to chronic
      hypoxia exhibited an increase in both right ventricle pressure and weight by
      comparison to normoxic control animals but those variations were significantly
      diminished in dexfenfluramine-treated rats, indicating the moderating influence
      exerted by dexfenfluramine on chronic hypoxia-induced pulmonary hypertension and
      cardiac alterations. Thus, we report here the ability of dexfenfluramine to limit
      chronic hypoxia-induced pulmonary hypertension, emphasizing the importance of the
      time after the dexfenfluramine treatment discontinuation to assess the influence
      of this 5-HT receptor agonist on the development of chronic hypoxia-induced
      pulmonary hypertension.

PMID- 17026994
TI  - Effect of levofloxacin on serum glucose concentration in rats.
AB  - To clarify the mechanism of fluoroquinolone-induced abnormalities in blood
      glucose, the effect of levofloxacin on serum glucose concentration was
      investigated in rats. Rats received an intravenous injection of levofloxacin and
      their arterial blood was sampled periodically. The serum glucose concentration
      decreased after an injection of 100 mg/kg of levofloxacin, while it increased at
      levofloxacin 300 mg/kg. The serum immunoreactive insulin concentration increased
      as the dose of levofloxacin increased. The serum epinephrine concentration was
      rapidly elevated by levofloxacin at 300 mg/kg. The serum histamine concentration
      increased after injections of levofloxacin, 200 and 300 mg/kg. Diphenhydramine (1
      mg/kg) antagonized the hyperglycemia induced by 300 mg/kg of levofloxacin. In an
      in vitro study, the release of epinephrine from the adrenal medulla in the
      presence of levofloxacin was determined. Levofloxacin (300 microg/ml) did not
      affect epinephrine release from the adrenal medulla. Levofloxacin can induce
      hypoglycemia and hyperglycemia in rats. Levofloxacin can promote histamine
      release, leading to an increased serum epinephrine concentration and
      hyperglycemia.

PMID- 17026995
TI  - Antiaggressive effects of MPEP, a selective antagonist of mGlu5 receptors, in
      agonistic interactions between male mice.
AB  - mGlu5 receptors are highly concentrated in limbic brain structures involved in
      motivational and emotional behaviours. This study describes the effects of 2
      methyl-6-(phenylethylnyl)pyridine (MPEP; 5, 10, 15, 20 and 25 mg/kg, ip), a
      selective antagonist of the mGlu5 receptors, on agonistic behaviour elicited by
      isolation in male mice. Individually housed mice were exposed to anosmic
      opponents in a neutral area 30 min after drug administration. Besides other
      behaviours, the aggressive (threat and attack) and exploratory behaviours were
      evaluated during 10 min using an ethologically based analysis. MPEP produced a
      behavioural profile characterized by a notable decrement of offensive behaviours,
      accompanied by a significant increase of exploratory behaviours (nonsocial
      exploration and social investigation). These findings suggest a role for mGlu5
      receptors in aggression modulation.

PMID- 17026996
TI  - The motor-impairing effects of GABA(A) and GABA(B) agonists in gamma
      hydroxybutyrate (GHB)-treated rats: cross-tolerance to baclofen but not
      flunitrazepam.
AB  - gamma-Hydroxybutyrate (GHB) is believed to function as a neurotransmitter in the
      mammalian brain by binding to a GHB-specific binding site. In addition, GHB may
      also indirectly enhance the neuroinhibitory actions of gamma-aminobutyric acid
      (GABA) by converting to GABA at neuronal synapses. The purpose of the present
      study was to examine the effects of representative GABA(A) and GABA(B) receptor
      agonists in rats treated chronically with GHB. Using a rotorod apparatus, the
      motor-impairing effects of GHB, the indirect GABA(A) receptor agonist,
      flunitrazepam, and the direct GABA(B) receptor agonist, baclofen, were examined
      before, during and after chronic treatment with 1000 mg/kg GHB, b.i.d. Prior to
      chronic treatment, all three drugs produced dose-dependent decreases in motor
      performance at low (8 rpm) and high (32 rpm) rotational speeds. Chronic treatment
      with GHB significantly decreased the potency of baclofen at both speeds, but did
      not alter the potency of either GHB or flunitrazepam. Following termination of
      chronic treatment, the potency of baclofen increased significantly at both speeds
      and returned to that observed prior to chronic treatment. These data indicate
      that chronic treatment with GHB confers tolerance to a GABA(B) receptor agonist
      under conditions in which tolerance is not conferred to a GABA(A) receptor
      agonist. These findings are consistent with the in vivo behavioral profile of
      GHB, which reveals a greater role for GABA(B) receptors than for GABA(A)
      receptors in its behavioral effects.

PMID- 17026997
TI  - In situ detection of global DNA hypomethylation in exfoliative urine cytology of
      patients with suspected bladder cancer.
AB  - Global DNA hypomethylation is a common phenomenon in bladder cancer. Therefore we
      investigated whether it is possible to detect and assess global DNA
      hypomethylation in bladder cancer using a specific monoclonal antibody for 5
      methyl-cytosine. Cytospins from exfoliative urine cytology specimens of patients
      with bladder cancer or a history of bladder cancer, control patients with benign
      urological diseases and of young healthy volunteers were analyzed. Urothelial
      carcinoma (UC) cells showed various degrees of nuclear destaining indicating
      global DNA hypomethylation whereas all specimens from healthy volunteers showed
      granular nuclear staining indicating regular methylation of repeated DNA
      sequences. Lowest 5-methylcytosine immunostaining scores were observed in
      carcinoma cells and a statistically significant difference was observed between
      urothelial cells of healthy controls or patients with benign disease compared to
      bladder cancer patients (p<0.01, p<0.05, respectively). In UC cases even
      morphologically normal urothelial cells often displayed evident hypomethylation.
      Likewise, in patients with a history of UC, but no cystoscopic evidence of
      recurrence, morphologically non-malignant urothelial cells presented with some
      degree of demethylation. Our results strongly support the hypothesis of early
      global demethylation in bladder cancer. Immunocytochemical staining with the 5
      methylcytosine antibody allows simultaneous individual assessment of nuclear
      morphology and methylation status of a given sample.

PMID- 17026999
TI  - The murine TRAIL receptor signals caspase-independent cell death through
      ceramide.
AB  - Death receptors such as the 55 kDa tumor necrosis factor (TNF) receptor (TNF-R55)
      or Fas can initiate both apoptotic (caspase-dependent) and caspase-independent
      routes to programmed cell death (PCD). Here, we demonstrate for the first time
      that the single murine receptor for (TNF)-related apoptosis-inducing ligand
      (mTRAIL-R2) can induce a caspase-independent form of PCD with necrosis-like
      features in addition to apoptosis. Analysis of morphological and cellular
      features of caspase-independent PCD in response to TRAIL and TNF suggests that
      mTRAIL-R2 and TNF-R55 elicit caspase-independent PCD through similar pathways,
      although without participation of cathepsins. Cells overexpressing acid
      ceramidase (AC), an enzyme that metabolizes the sphingolipid ceramide, show
      enhanced survival from TRAIL-induced caspase-independent PCD but not from
      apoptosis, implicating a function of ceramide as a key mediator in caspase
      independent PCD (but not apoptosis) induced by mTRAIL-R2. In concert with the
      enhanced resistance of AC-overexpressing cells against caspase-independent PCD
      induced by TNF, our results suggest that ceramide acts as a common mediator of
      caspase-independent PCD caused by death receptors such as mTRAIL-R2 and TNF-R55.

PMID- 17026998
TI  - Requirements for proximal tubule epithelial cell detachment in response to
      ischemia: role of oxidative stress.
AB  - Sublethal renal ischemia induces tubular epithelium damage and kidney
      dysfunction. Using NRK-52E rat proximal tubular epithelial cells, we have
      established an in vitro model, which includes oxygen and nutrients deprivation,
      to study the proximal epithelial cell response to ischemia. By means of this
      system, we demonstrate that confluent NRK-52E cells lose monolayer integrity and
      detach from collagen IV due to: (i) actin cytoskeleton reorganization; (ii) Rac1
      and RhoA activity alterations; (iii) Adherens junctions (AJ) and Tight junctions
      (TJ) disruption, involving redistribution but not degradation of E-cadherin, beta
      catenin and ZO-1; (iv) focal adhesion complexes (FAC) disassembly, entangled by
      mislocalization of paxillin and FAK dephosphorylation. Reactive oxygen species
      (ROS) are generated during the deprivation phase and rapidly balanced at recovery
      involving MnSOD induction, among others. The use of antioxidants (NAC) prevented
      FAC disassembly by blocking paxillin redistribution and FAK dephosphorylation,
      without abrogating AJ or TJ disruption. In spite of this, NAC did not show any
      protective effect on cell detachment. H(2)O(2), as a pro-oxidant treatment,
      supported the contribution of ROS in tubular epithelial cell-matrix but not cell
      cell adhesion alterations. In conclusion, ROS-mediated FAC disassembly was not
      sufficient for the proximal epithelial cell shedding in response to sublethal
      ischemia, which also requires intercellular adhesion disruption.

PMID- 17027000
TI  - Thy-1, via its GPI anchor, modulates Src family kinase and focal adhesion kinase
      phosphorylation and subcellular localization, and fibroblast migration, in
      response to thrombospondin-1/hep I.
AB  - Normal fibroblast subpopulations have differential surface expression of the GPI
      linked raft protein Thy-1, which correlates with differences in cellular adhesion
      and migration in vitro. Thrombospondin-1 (TSP-1) induces an intermediate state of
      adhesion in fibroblasts and other cells which facilitates migration. TSP-1 and
      the hep I peptide derived from the amino-terminal/heparin-binding domain of TSP-1
      induce disassembly of cellular focal adhesions. Our lab previously reported that
      the induction of focal adhesion disassembly in fibroblasts by TSP-1 or by hep I
      requires surface expression of Thy-1, as well as lipid raft integrity and Src
      family kinase (SFK) signaling. We now report that TSP-1/hep I-induced fibroblast
      migration requires Thy-1 expression and FAK phosphorylation, and that following
      TSP-1/hep I stimulation, Thy-1 associates with FAK and SFK in a lipid raft
      dependent manner. Furthermore, the GPI anchor of Thy-1, which localizes the
      protein to specific lipid raft microdomains, is necessary for hep I-induced FAK
      and SFK phosphorylation, focal adhesion disassembly, and migration. This is the
      first report of an association between Thy-1 and FAK. Thy-1 modulates SFK and FAK
      phosphorylation and subcellular localization, promoting focal adhesion
      disassembly and migration in fibroblasts, following exposure to TSP-1/hep I.

PMID- 17027002
TI  - Expressions of Rac1, Tiam1 and Cdc42 in retinoblastoma.
AB  - The Rho GTPases are the molecular regulators of the cell motility processes and
      are involved in cell cycle progression and gene transcription. We studied the
      expression of Rho-like GTPases molecules, particularly Rac, Tiam1 and cdc42, in
      retinoblastoma and correlated these with clinicopathological parameters of the
      tumors. Sixty-seven tumors were included which were divided in to two groups;
      group A: tumors with optic nerve/choroidal/orbital invasion (n=35) and group B:
      tumors with no invasion (n=32). Immunohistochemistry was done on paraffin
      sections for all the proteins and were confirmed by Western blot on fresh tumor
      samples. In group A tumors, Rac was positive in 10/35 (28%), cdc42 was positive
      in 12/35 (34%) and Tiam1 was positive in 30/35 (85%) tumors. In group 2 tumors,
      Rac was positive in 5/32 (15%), cdc42 was positive in 4/32 (12%) and Tiam1 was
      positive in 30/32 (93%) tumors. Two groups (both invasive and non-invasive
      tumors) showed decreased expression of Rac1 and cdc42 whereas Tiam1 was
      significantly expressed in invasive tumors compared to non-invasive tumors
      (P<0.0001). We observed a 70K cleavage product of Tiam1 along with an 110K
      product by blotting in RB samples. Caspase-3 was also demonstrated in RB samples,
      which showed Tiam1 cleavage products. This is the first study that showed the
      expression patterns of Rac, cdc42 and Tiam1 in retinoblastoma tumors. Thus,
      further studies are required to prove the involvement of caspase-3 in the
      cleavage of Tiam1 in vitro in RB cells and to trace out alternative pathways
      involved in tumor progression.

PMID- 17027003
TI  - Clonorchis sinensis: codon usage in nuclear genes.
AB  - Codon usage in Clonorchis sinensis was analyzed using 12,515 codons from 38
      coding sequences. Total GC content was 49.83%, and GC1, GC2 and GC3 contents were
      56.32%, 43.15% and 50.00%, respectively. The effective number of codons converged
      at 51-53 codons. When plotted against total GC content or GC3, codon usage was
      distributed in relation to GC3 biases. Relative synonymous codon usage for each
      codon revealed a single major trend, which was highly correlated with GC content
      at the third position when codons began with A or U at the first two positions.
      In codons beginning with G or C base at the first two positions, the G or C base
      rarely occurred at the third position. These results suggest that codon usage is
      shaped by a bias towards G or C at the third base, and that this is affected by
      the first and second bases.

PMID- 17027001
TI  - Proteasome-dependent regulation of signal transduction in retinal pigment
      epithelial cells.
AB  - As in many other types of cells, retinal pigment epithelial (RPE) cells have an
      active ubiquitin-proteasome pathway (UPP). However, the function of the UPP in
      RPE remains to be elucidated. The objective of this study is to determine the
      role of the UPP in controlling the levels and activities of transcription factors
      hypoxia-inducible factor (HIF) and NF-kappaB. We inhibited the UPP with
      proteasome-specific inhibitors and determined the activation of HIF and NF-kappaB
      as well as the expression and secretion of pro-angiogenic factors. HIF-1alpha was
      not detectable in ARPE-19 cells under normal culture conditions. However, when
      proteasome activity was inhibited, HIF-1alpha accumulated in RPE in a time
      dependent manner. Consistent with accumulation of HIF-1alpha in the cells, levels
      of mRNA for vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2)
      in RPE were up to 7-fold higher upon inhibition of the proteasome. Proteasome
      inhibition was also associated with a 2-fold increase in levels of mRNA for
      angiopoietin-1 (Ang-1). ARPE-19 cells secrete significant levels of VEGF under
      normal culture conditions. Inhibition of proteasome activity increased the
      secretion of VEGF by 2-fold. In contrast to the increase in HIF activity, NF
      kappaB activation was reduced by proteasome inhibition. In addition, the
      expression and secretion of monocyte chemoattractant protein-1 (MCP-1) by RPE
      were substantially attenuated by the inhibition of proteasome activity. These
      data demonstrate that the UPP plays an important role in modulating the
      activities of HIF and NF-kappaB in the RPE. Consequences of an impairment of the
      UPP include accumulation of HIF-1alpha and diminished NF-kappaB activation, which
      lead to enhanced expression and secretion of pro-angiogenic factors and
      attenuated expression of MCP-1. Taken together, these data predict that the
      impairment of the UPP could lead to the development of AMD-related phenotypes.

PMID- 17027004
TI  - Leishmania mexicana amazonensis: development of a peptide tag useful for labeling
      and purifying biotinylated recombinant proteins.
AB  - A number of peptide tags are available to facilitate the characterization of
      recombinant proteins. We have tested the bacterial oxaloacetate decarboxylase
      biotinylation domain for its efficacy in tagging recombinant proteins in vivo in
      Leishmania. To achieve efficient biotinylation, Leishmania also had to be co
      transformed with the gene for bacterial biotin protein ligase (birA gene
      product). The recombinant chimeric protein could be detected on blots probed with
      avidin-horseradish peroxidase and purified on immobilized monomeric avidin
      resins.

PMID- 17027005
TI  - Antigen receptor regulation of phosphoinositide-dependent kinase 1 pathways
      during thymocyte development.
AB  - Phosphoinositide-dependent kinase 1 (PDK1) is essential for T cell development
      but little is know about the stimuli that regulate PDK1 signaling in vivo. The
      thymus contains a heterogeneous mixture of cells at different stages of
      development making it difficult to use biochemical techniques to examine the
      activity of PDK1 pathways as thymocytes develop in situ. Herein, we use a single
      cell assay to quantify activation of the PDK1 target kinase ribosomal S6 kinase 1
      (S6K1) in different murine thymocyte subsets immediately ex vivo. This technique
      allows an assessment of S6K1 activation as thymocytes respond to developmental
      stimuli in vivo. These studies reveal that only a small percentage of thymocytes
      show evidence for activation of PDK1 mediated signaling in situ. The thymic
      subpopulations that contain active PDK1/S6K1 are those known to be responding to
      signaling by the pre T cell receptor and the mature alpha/beta T cell antigen
      receptor (TCR). Moreover, loss of antigen receptor signaling in T cell
      progenitors that cannot rearrange their TCR beta locus prevents in vivo
      activation of S6K1. The present data identifying antigen receptor signaling as a
      key activator of PDK1 mediated signaling afford a molecular explanation for the
      important role of this molecule in T cells.

PMID- 17027006
TI  - Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and
      their co-localization in Lewy bodies.
AB  - TPPP/p25, a flexible unstructured protein, binds to tubulin and induces aberrant
      microtubule assemblies. We identified hereby glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) as a new interacting partner of TPPP/p25. The
      immunoprecipitation and affinity chromatographic experiments with bovine brain
      cell-free extract revealed that the interaction was salt and NAD(+) sensitive
      while ELISA showed resistant and firm association of the two isolated proteins.
      In transfected HeLa cells at low expression level of EGFP-TPPP/p25, while the
      green fusion protein aligned at the microtubular network, GAPDH distributed
      uniformly in the cytosol. However, at high expression level, GAPDH co-localized
      with TPPP/p25 in the aggresome-like aggregate. Immunohistochemistry showed
      enrichment of TPPP/p25 and GAPDH within the alpha-synuclein positive Lewy body.

PMID- 17027007
TI  - Mechanisms of sexual selection: sexual swellings and estrogen concentrations as
      fertility indicators and cues for male consort decisions in wild baboons.
AB  - Male mate-guarding episodes ('consortships'), are taxonomically widespread, yet
      costly to individual males. Consequently, males should bias consortships toward
      females with whom the probability of conception is high. We combined data on
      consortships with visual scoring of sexual swellings and assays of fecal estrogen
      concentrations (fE) in a wild population of baboons (Papio cynocephalus) to test
      the hypotheses that sexual swellings are reliable indicators of (1) within-cycle
      timing of ovulation, (2) differences in conception probability among females that
      differ in maturational stage, and (3) conceptive versus non-conceptive cycles of
      parous females. We also evaluated whether adult males might rely on swellings or
      other estrogen-dependent signals (e.g., fE) for mate-guarding decisions. We found
      that sexual swellings reflected conception probability within and among cycles.
      Adult males limited their consortships to the turgescent phase of cycles, and
      consorted more with adult females than with newly cycling adolescents. The
      highest ranking (alpha) males discriminated more than did males of other ranks;
      they (1) limited their consortships to the 5-day peri-ovulatory period, (2)
      consorted more with adult than with adolescent females, and (3) consorted more
      with adult females on conceptive cycles than on non-conceptive cycles, all to a
      greater extent than did males of other ranks. Male mate choice based on sexual
      swellings and other estrogenic cues of fertility may result in sexual selection
      on these female traits and enhance dominance-based reproductive skew in males.
      Alpha males are the least constrained in their mating behavior and can best take
      advantage of these cues to mate selectively.

PMID- 17027008
TI  - The prefrontal cortex, gonadal hormones and memory.

PMID- 17027009
TI  - Fast gas chromatographic/mass spectrometric determination of diuretics and
      masking agents in human urine: Development and validation of a productive
      screening protocol for antidoping analysis.
AB  - An analytical procedure was developed for the fast screening of 16 diuretics
      (acetazolamide, althiazide, amiloride, bendroflumethiazide, bumetanide, canrenoic
      acid, chlorthalidone, chlorthiazide, clopamide, ethacrynic acid, furosemide,
      hydrochlorthiazide, hydroflumethiazide, indapamide, triamterene,
      trichlormethiazide) and a masking agent (probenecid) in human urine. The whole
      method involves three analytical steps, including (1) liquid/liquid extraction of
      the analytes from the matrix, (2) their reaction with methyl iodide at 70 degrees
      C for 2 h to form methyl derivatives, (3) analysis of the resulting mixture by
      fast gas chromatography/electron impact mass spectrometry (fast GC/EI-MS). The
      analytical method was validated by determining selectivity, linearity, accuracy,
      intra and inter assay precision, extraction efficiencies and signal to noise
      ratio (S/N) at the lowest calibration level (LCL) for all candidate analytes. The
      analytical performances of three extraction procedures and five combination of
      derivatization parameters were compared in order to probe the conditions for
      speeding up the sample preparation step. Limits of detection (LOD) were evaluated
      in both EI-MS and ECNI-MS (electron capture negative ionization mass
      spectrometry) modes, indicating better sensitivity for most of the analytes using
      the latter ionization technique. The use of short columns and high carrier gas
      velocity in fast GC/MS produced efficient separation of the analytes in less than
      4 min, resulting in a drastic reduction of the analysis time, while a resolution
      comparable to that obtained from classic GC conditions is maintained. Fast
      quadrupole MS electronics allows high scan rates and effective data acquisition
      both in scan and selected ion monitoring modes.

PMID- 17027010
TI  - Reaction product analysis by high-performance liquid chromatography-solid-phase
      extraction-nuclear magnetic resonance Application to the absolute configuration
      determination of naturally occurring polyyne alcohols.
AB  - The absolute configuration of secondary hydroxy functions of seven natural
      occurring polyyne derivatives has been elucidated by the application of Mosher
      method of diastereomeric methoxy-2-trifluoromethyl-phenylacetyl (MTPA) ester
      formation. High-performance liquid chromatography with diode array detection
      (HPLC-DAD) of the reaction mixture using a water/acetonitrile gradient allowed
      monitoring the reaction progress. Coupling of high-performance liquid
      chromatography to solid-phase extraction combined with nuclear magnetic resonance
      (HPLC-SPE-NMR) was utilized to generate highly reproducible (1)H and (19)F NMR
      data needed as input for the absolute configuration determination based on the
      analysis of relative shift differences. Chromatographic peaks of reaction
      substrates and reaction products bearing less 10mug analyte were trapped on SPE
      cartridges with the aid of water as makeup solvent. Deuterated chloroform was
      used to elute and transfer the peak content from the SPE to the 60mul flow cell
      of a 500MHz NMR spectrometer. For each analyte (1)H NMR spectra were obtained
      within 15min. Additionally (19)F NMR spectra were recorded for selected analytes
      in the same timeframe. Based on the obtained NMR data, the absolute configuration
      of all polyynes under investigation was successfully designated.

PMID- 17027011
TI  - Development of an online two-dimensional nano-scale liquid chromatography/mass
      spectrometry method for improved chromatographic performance and hydrophobic
      peptide recovery.
AB  - An online two-dimensional (2D) strong cation-exchange (SCX)/reversed-phase (RP)
      nano-scale liquid chromatography/mass spectrometry (nanoLC/MS) method was
      developed for improved separation and hydrophobic peptide recovery. Sharper and
      more symmetric RP peaks were observed with the use of a "band re-focusing
      method", in which an analytical RP column with more hydrophobicity than the RP
      trap column was used in the system. To recover hydrophobic peptides still
      unreleased from the SCX column after a conventional salt step gradient due to
      hydrophobic interaction, a RP step gradient from 10% to 30% acetonitrile (ACN)
      was applied to the SCX column in the presence of a high salt concentration
      following the salt gradient. There were 301 unique hydrophobic E. coli peptides
      identified from the RP fractions. These peptides, which were 19% of all E. coli
      peptides identified from a 2D run, would not have been identified without the
      application of the RP gradient to the SCX column.

PMID- 17027012
TI  - Identification of complex mixtures of sphingolipids in the stratum corneum by
      reversed-phase high-performance liquid chromatography and atmospheric pressure
      photospray ionization mass spectrometry.
AB  - Sphingolipids, such as ceramides and cerebrosides, are important molecules in the
      formation and maintenance of the epidermal barrier to water vapor diffusion. In
      this paper we explore a new method to identify the sphingolipids found in the
      stratum corneum (SC), the outer layer of the epidermis, of House sparrows living
      in Saudi Arabia using reversed-phase high-performance liquid chromatography
      (HPLC) coupled with atmospheric pressure photo-ionization mass spectrometry (APPI
      MS). First, using thin layer chromatography (TLC) we found that the SC contains
      ceramides, cerebrosides, and free fatty acids along with smaller amounts of
      cholesterol. Knowing the classes of sphingolipids present in the SC markedly
      reduced the number of possible molecules present. Then, we identified each
      sphingolipid molecule in our sample by both negative and positive mode of APPI
      MS. We confirmed our identifications by generation of accurate mass data, and by
      examination of MS/MS spectra for selected molecules. Using APPI-MS, we identified
      7 families of cerebrosides, for a total of 97 molecular species, and 4 families
      of ceramides, for a total of 79 molecules, in the SC of House sparrows, a wider
      array than would be found in mammals. Carbon chain lengths of fatty acids in the
      sphingolipids were longer than those that have been reported for mammalian SC;
      chain lengths of over 40 carbons were common. We also compared our estimates of
      the quantity of lipids in the SC obtained by HPLC/MS with those from TLC.
      Estimates of the amount of total ceramides and cerebrosides using TLC differed
      from those obtained by HPLC/MS by +0.95% and -2.5%, respectively. We conclude
      that our protocol using reversed-phase HPLC and APPI-MS is an useful method of
      analyzing complex mixtures of sphingolipids in the SC.

PMID- 17027013
TI  - Monodisperse hollow titania nanospheres prepared using a cationic colloidal
      template.
AB  - Titania-coated polymeric nanoparticles were synthesized based on the cationic
      colloidal particles which were prepared by surfactant-free emulsion
      copolymerization of styrene and butylacrylate in the presence of a cationic
      monomer, methacryloxyethyltrimethyl ammonium chloride (MOTAC) using
      azobis(isobutylamidine)hydrochloride (AIBA) as an initiator. These cationic
      particles were stabilized by poly(vinylpyrrolidone) (PVP). Then, these particles
      were dispersed in ethanol and mixed with titanium(IV) butoxide. Negatively
      charged titania precursors were rapidly hydrolyzed onto the cationic surfaces of
      colloidal particles. Subsequently, the samples were heated to 450 degrees C to
      form anatase TiO2 and to remove the colloidal template, which resulted in hollow
      nanospheres. The hollow titania particles were characterized with zeta analyzer,
      transmission electron microscopy, scanning electron microscopy, light scattering,
      X-ray diffraction, thermogravimetric analysis and FT-IR.

PMID- 17027014
TI  - Layered double hydroxides as potential chromate scavengers.
AB  - The LDH of Ni with Fe, having the formula Ni(1-x)Fe(x)(OH)2(A(n-))(x/n)yH2O (A =
      NO3-, Cl-; x = 0.25, 0.33), scavenges CrO4(2-) ions from solution throughout the
      concentration range examined (0.00625-0.25 N). The CrO4(2-) uptake capacity is
      independent of the anion in the starting LDH but is higher when x = 0.25 (3.60
      meq g(-1)) as compared to x = 0.33 (2.40 meq g(-1)). These values are higher than
      those observed for control compounds beta-Ni(OH)2 (1.86 meq g(-1)) and FeO(OH)
      (1.26 meq g(-1)), which do not have any interlayer chemistry, showing that
      chromate uptake takes place by its incorporation in the interlayer region by a
      stoichiometric anion-exchange reaction, rather than by adsorption. Nevertheless,
      the interaction between the LDH and the chromate ions is weak. The weak
      interaction is due to the mismatch between the symmetry of the chromate ions and
      the symmetry of the interlayer site, which introduces turbostratic disorder in
      the chromate-intercalated LDHs. The chromate ions can be completely leached out
      by soaking the LDH in a sodium carbonate solution.

PMID- 17027015
TI  - Correlation between surface tension and critical temperatures of liquid metals.
AB  - The inter-relationship of surface tension sigma, molar volume V, and critical
      temperature Tc has been examined using experimental values for eighteen liquid
      metals. Hard-sphere diameters a correlate with the equation a(5/2) = 8.9733 x 10(
      19) V (sigma/Tc)(1/4) - 1.0459 x 10(-25). Unknown Tc may be estimated using
      surface tension and liquid density values.

PMID- 17027016
TI  - Relation between P-wave dispersion and left ventricular geometric patterns in
      newly diagnosed essential hypertension.
AB  - AIM: P-wave durations and P-wave dispersion (PD) are considered to reflect the
      heterogeneous conduction in atria. The aim of this study was to investigate PD
      and P-wave duration in different left ventricle geometric patterns of
      hypertensive patients. METHODS: One hundred forty-nine consecutive patients with
      newly diagnosed essential hypertension and 29 healthy control groups were
      included in the study. The maximum and minimum P-wave duration (Pmax and Pmin,
      respectively) and PD were measured from the 12-lead surface electrocardiogram.
      Echocardiographic examination was also performed in all subjects. Four different
      geometric patterns were identified in hypertensive patients according to left
      ventricular mass index (LVMI) and relative wall thickness. RESULTS: P-wave
      dispersion was longer in concentric remodeling (CR), concentric hypertrophy (CH),
      and eccentric hypertrophy (EH) groups when compared with the control group (P =
      .009, P < .001, P < .001, respectively). P-wave dispersion of normal left
      ventricle (NLV) geometric pattern was not different from that of the control
      group. Patients with NLV geometric pattern had shorter PD than patients who had
      CH and EH (NLV vs CH, P < .001; NLV vs EH, P = .025). P-wave dispersion of the
      NLV group was not different from that of the CR group. Patients with CR had also
      shorter PD than patients who had CH (P = .002). In bivariate analysis, there was
      a significant correlation between PD with left ventricle geometry, body surface
      area, LVMI, and relative wall thickness. In multiple linear regression analysis,
      PD was independently correlated only with LVMI (beta = .425, P < .001).
      CONCLUSIONS: P-wave dispersion is independently associated with LVMI rather than
      left ventricle geometry and relative wall thickness in hypertensive patients.
      Thus, it is increased particularly in patients with CH and EH.

PMID- 17027017
TI  - Effect of clinical variables on the correlation between amount of ST elevation
      and myocardial scintigraphic perfusion defect during coronary occlusion.
AB  - PURPOSE: We investigated if the correlation between the amount of ST elevation
      (STE) and myocardial ischemia could be altered by variables such as hypertension
      or body mass index (BMI). METHODS: A 12-lead electrocardiogram and a technetium
      99m tetrofosmin injection were performed during balloon coronary occlusion in 34
      patients with single-vessel disease. RESULTS: The sum of STE correlated with
      scintigraphic extent of ischemia (r = 0.441; P = .009), but this correlation
      improved significantly in men and patients with BMI of 28 kg/m2 or less and was
      highest in nonhypertensive patients (r = 0.763; P < .001). In contrast, it was
      poor in women and patients with BMI greater than 28 kg/m2 or arterial
      hypertension, being lowest in the latter subset (r = 0.110; P = .664). Moreover,
      8 (80%) of 10 patients with extensive hypoperfusion but with low SigmaSTE (< or
      =20 mm) were hypertensive. CONCLUSIONS: If confirmed by larger studies,
      electrocardiographic underestimation of transmural ischemia during coronary
      occlusion in patients with hypertension or increased BMI may lead to adjustments
      in STE criteria for reperfusion therapy.

PMID- 17027018
TI  - Electrocardiographic changes by accidental hypothermia in an urban and a tropical
      region.
AB  - BACKGROUND: Hypothermia is defined as a condition in which core temperature
      (rectal, esophageal, or tympanic) reaches values below 35 degrees C. This may be
      accidental, metabolic, or therapeutic. The accidental form is frequent in cold
      climate countries and rare in those with tropical or subtropical climate. The aim
      of this study was to evaluate electrocardiographic changes of patients with
      accidental hypothermia. METHODS: In 59 patients with hypothermia, the following
      electrocardiogram parameters were analyzed: rhythm and heart rate (HR), P-wave
      characteristics, PR-interval duration, QRS-complex duration, presence of J wave
      and its location characteristics, polarity, voltage, aspect and its correlation
      with the degree of hypothermia, changes in T wave regarding its polarity and
      characteristics, duration of the QT interval corrected for HR using both Bazett
      and Friderica formulas, and possible presence of both supraventricular and
      ventricular arrhythmias were independently and blindly analyzed in the tracings
      by experienced cardiologists. RESULTS: In 6 patients, electrocardiogram was
      normal. Sinus bradycardia was observed in 52.5% of the patients. J wave was
      present in 51 patients, and its voltage correlated inversely and was
      statistically significantly with the core temperature. Changes in T wave were
      observed in 47.4% of the cases. QT interval, adjusted for HR, was prolonged in
      72.8% of the cases. Idioventricular rhythm was found in 6 cases, total
      atrioventricular block in 3 cases, and junctional rhythm and atrial fibrillation
      in 2 patients. CONCLUSIONS: Electrocardiogram changes in accidental hypothermia
      are frequent and characteristic for this entity improving diagnosis in usually
      unconscious patients, and in many cases, it may be the diagnostic clue in
      patients with conscience deficit in emergency units, even in patients from a
      tropical climate where the population at risk may be exposed to temperatures
      below 20 degrees C.

PMID- 17027019
TI  - Characterization and incidence of inducible monomorphic ventricular tachycardia
      in a postinfarction rabbit model.
AB  - OBJECTIVE: Ventricular tachycardia (VT), occurring late after myocardial
      infarction, is an important cause of sudden death. Animal models are useful for
      the investigation of this arrhythmia. The aim of this study is to develop and
      characterize a model of late postinfarction monomorphic VT in the rabbit. METHODS
      AND RESULTS: Myocardial infarction was created by ligation of the left circumflex
      artery. Cardiac electrophysiologic studies were performed 10 to 17 days
      postinfarction in 39 rabbits, in 10 sham-operated rabbits, and 6 control rabbits.
      Ventricular tachycardia was defined as a broad-complex tachycardia with a cycle
      length of more than 100 milliseconds, a duration of more than 10 seconds, and
      monomorphic QRS complexes. Using programmed stimulation, we induced VT in 9
      rabbits (23%) in the infarct group but in none of the sham or control animals.
      The mean infarct size was 23% +/- 9% (mean +/- SD) of the left ventricle.
      CONCLUSION: Coronary ligation in the rabbit creates a substrate, which allows the
      induction of sustained monomorphic VT with programmed stimulation. Monomorphic VT
      is not inducible in rabbits without myocardial infarction. This model might allow
      the testing of interventions that reduce the incidence of VT late after
      myocardial infarction.

PMID- 17027020
TI  - Production of calmodulin-tagged proteins in Drosophila Schneider S2 cells: a
      novel system for antigen production and phage antibody isolation.
AB  - We report the development of an expression system for the production of soluble,
      calmodulin (CaM)-tagged proteins in Drosophila Schneider S2 cells and the
      subsequent use of these proteins for the selection of phage displayed antibodies.
      The CaM-tag permitted the purification of recombinant protein to >90% purity in a
      single step at yields of >20 mg/l. Using platelet glycoprotein VI (GP6) as a
      model, we demonstrated that the recombinant CaM-tagged protein was post
      translationally N-glycosylated and had identical ligand specificity to native
      protein. A novel selection strategy, exploiting the CaM tag, was then used to
      isolate four single chain Fv fragments (scFvs) specific for GP6 from a non-immune
      phage display library. In contrast to other selection methods, which can result
      in antibodies that do not recognise native protein, all of the scFvs we selected
      bound cell surface expressed GP6. In conclusion, the production of CaM-tagged
      proteins in Drosophila Schneider S2 cells and the selection strategy reported
      here offer advantages over previously published methods, including simple culture
      conditions, rapid protein purification, specific elution of phage antibodies and
      preferential selection of phage antibodies that recognise native, cell surface
      expressed protein.

PMID- 17027021
TI  - Amplification of the antigen-antibody interaction from quartz crystal
      microbalance immunosensors via back-filling immobilization of nanogold on
      biorecognition surface.
AB  - A new quartz crystal microbalance immunoassay method based on a novel transparent
      immunoaffinity reactor was developed for clinical immunoassay. To construct such
      an affinity reactor, resonators with a frequency of 10 MHz were fabricated by
      affinity binding of functionalized gold nanoparticles (nanogold) to quartz
      crystal with immobilized specific ligand for the label-free analysis of the
      affinity reaction between a ligand and its receptor. [Recombinant human tumor
      markers, carcinoembryonic antigen (CEA) was chosen as a model ligand.] The
      binding of target molecules onto the immobilized antibodies decreased the
      sensor's resonant frequency, and the frequency shift was proportional to the CEA
      concentration in the range of 3.0-50 ng/ml with a detection limit of 1.5 ng/ml at
      a signal/noise ration of 3. A glycine-HCl solution (pH 2.3) was used to release
      antigen-antibody complexes from the biorecognition surface. Good reusability was
      exhibited. Moreover, spiking various levels of CEA into normal human sera was
      diagnosed using the proposed immunoassay. Analytical results show the precision
      of the developed immunoassay is acceptable, implying a promising alternative
      approach for detecting CEA in clinical immunoassay. Compared with the
      conventional enzyme-linked immunosorbent assay, the proposed immunoassay system
      was simple and rapid without multiple labeling and separation steps. Importantly,
      the proposed immunoassay system could be further developed for the immobilization
      of other antigens or biocompounds.

PMID- 17027022
TI  - Epizootiological studies of Amblyospora camposi (Microsporidia: Amblyosporidae)
      in Culex renatoi (Diptera: Culicidae) and Paracyclops fimbriatus fimbriatus
      (Copepoda: Cyclopidae) in a bromeliad habitat.
AB  - The epizootiology of Amblyospora camposi was studied in a natural population of
      Culex renatoi, a bromeliad-inhabiting mosquito, and its intermediate host,
      Paracyclops fimbriatus fimbriatus, over a 2-year period. Twenty Eryngium cabrerae
      plants were sampled monthly from January 2003 to January 2005 and the prevalence
      of A. camposi in P.f. fimbriatus and Cx. renatoi populations was determined. The
      monthly prevalence rates of meiospore infections in Cx. renatoi larvae never
      exceeded 5.5% and was detected in 50% of the monthly samples. Meiospores were
      available in plants over the course of the study at a mean concentration of 2 x
      10(4) meiospores/ml. Within each plant the parasite was maintained by horizontal
      transmission. P.f. fimbriatus with vegetative stages and mature spores were found
      regularly in bromeliads suggesting efficient meiospore infectivity to field
      copepod populations. The mean concentration of spores from copepods found in
      plants was 8 x 10(2) spores/ml. Infections in copepods were detected in 54% of
      the monthly samples with a prevalence rate ranging from 0.55 to 17.4% and an
      overall average of 5.1%. Vegetative stages in fourth instar mosquito larvae
      (probably derived from the horizontal pathway via spores formed in copepods) were
      detected in 12.5% of the monthly samples with an overall prevalence rate of 1.1%.
      Infections in female and male adults were detected in 20.8% of the monthly
      samples with an overall average of 4.1% and 6.8%, respectively.

PMID- 17027023
TI  - Molecular and phenotypic characterisation of Bacillus thuringiensis isolated
      during epizootics in Cydia pomonella L.
AB  - Twelve Bacillus thuringiensis strains were isolated from intestinal tracts of
      Cydia pomonella larvae during epizootics in different laboratory insect culture
      lines. Phenotypic and genetic similarity of these isolates, together with two
      cultured from Leucoma salicis larvae and 14 reference B. thuringiensis strains
      were determined. The epizootic bacteria did not form a single group based on
      numerical analysis of biochemical properties. Simple RAPD method with only one
      primer does not allow estimating the genetic similarity of B. thuringiensis
      strains. We propose a novel strategy based on combining several DNA patterns
      obtained by RAPD technique with different primers for B. thuringiensis typing.
      Majority of infections in the C. pomonella culture lines were caused by bacteria
      with different genotypes. However, two isolates cultured from infected insects at
      different time (one strain was isolated in 1990 and the other in 1992) had
      identical DNA fingerprint that suggested a possibility of these bacteria to
      survive in the laboratory and to cause infections in different years. The results
      of SDS-PAGE of whole-cell proteins revealed a possibility to apply protein
      profile analysis in epidemiological investigations of infections caused by B.
      thuringiensis. Strains with identical DNA patterns had very similar whole-cell
      protein profiles.

PMID- 17027024
TI  - Mechanical unloading of the heart activates the calpain system.
AB  - The mechanism for the decrease in cardiomyocyte size with mechanical unloading is
      unknown. The calpain system regulates cardiomyocyte atrophy. We obtained samples
      from failing human hearts at the time of implantation and explantation of a left
      ventricular assist device. For mechanical unloading, we also heterotopically
      transplanted rat or mouse hearts for 1 week. The effect of calpain inhibition on
      cardiac atrophy was assessed in transplanted hearts overexpressing calpastatin.
      We measured transcript levels of calpain 1 and 2 in the human and the rodent
      model, as well as calpain activity, a calpain-specific degradation product and
      cardiomyocyte size in the two rodent models. Mechanical unloading of the failing
      human heart significantly increased calpain 2 gene expression. Transcript levels
      of calpain 1 and 2, calpain activity and a calpain-specific degradation product
      all significantly increased in the unloaded rat heart. Unexpectedly, in hearts of
      animals overexpressing calpastatin, cardiomyocyte size also decreased. Mechanical
      unloading of the mammalian heart activates the calpain system, although other
      proteolytic systems may compensate for decreased calpain activity when
      calpastatin is overexpressed.

PMID- 17027026
TI  - How does endothelin-1 cause a sustained increase in intracellular sodium and
      calcium which lead to hypertrophy?

PMID- 17027025
TI  - Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia
      in rat hearts.
AB  - Cardiac pathologies are associated with increased late INa that contributes to
      the dysregulation of ion homeostasis and causes electrical and contractile
      dysfunction. This study was designed to test the hypothesis that an increased
      late sodium channel current (INa) leads to Ca2+ overload and left ventricular
      (LV) dysfunction, and thereby inhibition of late INa (e.g., by ranolazine)
      improves Ca2+ homeostasis and reduces LV dysfunction. Intracellular Ca2+
      ([Ca2+]i) and LV function were measured simultaneously in rat isolated perfused
      hearts. Augmentation of late INa with sea anemone toxin-II (ATX-II, 12 nM)
      increased diastolic [Ca2+]i (d[Ca2+]i), and impaired LV mechanical function, but
      had no effect on [Ca2+]i transient amplitude. Although ranolazine (4 and 9
      microM), an inhibitor of late INa, had no direct effects on d[Ca2+]i or LV
      function, it significantly reduced the deleterious effects of ATX-II. Global
      ischemia increased d[Ca2+]i and inhibited Ca2+ transient amplitude. During
      reperfusion, Ca2+ transient amplitude recovered fully, but d[Ca2+]i remained
      elevated and LV function was depressed, indicative of Ca2+ overload. Ranolazine
      (9 microM) reduced d[Ca2+]i accumulation during ischemia as well as reperfusion
      and improved recovery of LV function. These results show that augmentation of
      late INa with ATX-II or by ischemia is associated with diastolic Ca2+ overload
      and LV dysfunction. The beneficial effects of ranolazine in reducing Ca2+
      overload and LV mechanical dysfunction during ischemia/reperfusion is consistent
      with the inhibition of late INa mechanism of action.

PMID- 17027027
TI  - Selective binding of meiosis-specific yeast Hop1 protein to the holliday
      junctions distorts the DNA structure and its implications for junction migration
      and resolution.
AB  - Saccharomyces cerevisiae HOP1, which encodes a component of synaptonemal complex
      (SC), plays an important role in both gene conversion and crossing over between
      homologs, as well as enforces meiotic recombination checkpoint control over the
      progression of recombination intermediates. In hop1Delta mutants, meiosis
      specific double-strand breaks (DSBs) are reduced to 10% of the wild-type level,
      and at aberrantly late times, these DSBs are processed into inter-sister
      recombination intermediates. However, the underlying mechanism by which Hop1
      protein regulates these nuclear events remains obscure. Here we show that Hop1
      protein interacts selectively with the Holliday junction, changes its global
      conformation and blocks the dissolution of the junction by a RecQ helicase. The
      Holliday junction-Hop1 protein complexes are significantly more stable at higher
      ionic strengths and molar excess of unlabeled competitor DNA than complexes
      containing other recombination intermediates. Structural analysis of the Holliday
      junction using 2-aminopurine fluorescence emission, DNase I footprinting and
      KMnO4 probing provide compelling evidence that Hop1 protein binding induces
      significant distortion at the center of the Holliday junction. We propose that
      Hop1 protein might coordinate the physical monitoring of meiotic recombination
      intermediates with the process of branch migration of Holliday junction.

PMID- 17027028
TI  - Small-angle X-ray scattering reveals the solution structure of a
      bacteriophytochrome in the catalytically active Pr state.
AB  - Phytochromes are light-sensing macromolecules that are part of a two component
      phosphorelay system controlling gene expression. Photoconversion between the Pr
      and Pfr forms facilitates autophosphorylation of a histidine in the dimerization
      domain (DHp). We report the low-resolution structure of a bacteriophytochrome
      (Bph) in the catalytic (CA) Pr form in solution determined by small-angle X-ray
      scattering (SAXS). Ab initio modeling reveals, for the first time, the domain
      organization in a typical bacteriophytochrome, comprising an chromophore binding
      and phytochrome (PHY) N terminal domain followed by a C terminal histidine kinase
      domain. Homologous high-resolution structures of the light-sensing chromophore
      binding domain (CBD) and the cytoplasmic part of a histidine kinase sensor allows
      us to model 75% of the structure with the remainder comprising the phytochrome
      domain which has no 3D representative in the structural database. The SAXS data
      reveal a dimeric Y shaped macromolecule and the relative positions of the
      chromophores (biliverdin), autophosphorylating histidine residues and the ATP
      molecules in the kinase domain. SAXS data were collected from a sample in the
      autophosphorylating Pr form and reveal alternate conformational states for the
      kinase domain that can be modeled in an open (no-catalytic) and closed
      (catalytic) state. This model suggests how light-induced signal transduction can
      stimulate autophosphorylation followed by phosphotransfer to a response regulator
      (RR) in the two-component system.

PMID- 17027029
TI  - Thermus thermophilus bacteriophage phiYS40 genome and proteomic characterization
      of virions.
AB  - We determined the sequence of the 152,372 bp genome of phiYS40, a lytic tailed
      bacteriophage of Thermus thermophilus. The genome contains 170 putative open
      reading frames and three tRNA genes. Functions for 25% of phiYS40 gene products
      were predicted on the basis of similarity to proteins of known function from
      diverse phages and bacteria. phiYS40 encodes a cluster of proteins involved in
      nucleotide salvage, such as flavin-dependent thymidylate synthase, thymidylate
      kinase, ribonucleotide reductase, and deoxycytidylate deaminase, and in DNA
      replication, such as DNA primase, helicase, type A DNA polymerase, and predicted
      terminal protein involved in initiation of DNA synthesis. The structural genes of
      phiYS40, most of which have no similarity to sequences in public databases, were
      identified by mass spectrometric analysis of purified virions. Various phiYS40
      proteins have different phylogenetic neighbors, including myovirus, podovirus,
      and siphovirus gene products, bacterial genes and, in one case, a dUTPase from a
      eukaryotic virus. phiYS40 has apparently arisen through multiple acts of
      recombination between different phage genomes as well as through acquisition of
      bacterial genes.

PMID- 17027030
TI  - The alkali molten globule state of horse ferricytochrome c: observation of cold
      denaturation.
AB  - Here, we present the basic structural properties and the thermodynamic
      description of a previously unknown alkali molten globule state of horse
      "ferricytochrome c". Both sodium and guanidinium cations stabilize the alkali
      denatured state at pH 13, presumably by a charge screening mechanism. The Na(+)
      stabilized conformation (B state) clearly meets with the molecular organizational
      definition of the generic molten globule state. The B state exhibits highly
      cooperative thermal unfolding transitions monitored by both near and far-UV CD.
      Analyses of these transitions show substantial heat capacity change, suggesting
      that the hydrophobic effect contributes considerably to its energetic stability.
      At low salt concentration where molten globules are less stable, the B state
      undergoes reversible cold denaturation.

PMID- 17027031
TI  - Structure and action of the binary C2 toxin from Clostridium botulinum.
AB  - C2 toxin from Clostridium botulinum is composed of the enzyme component C2-I,
      which ADP-ribosylates actin, and the binding and translocation component C2-II,
      responsible for the interaction with eukaryotic cell receptors and the following
      endocytosis. Three C2-I crystal structures at resolutions of up to 1.75 A are
      presented together with a crystal structure of C2-II at an appreciably lower
      resolution and a model of the prepore formed by fragment C2-IIa. The C2-I
      structure was determined at pH 3.0 and at pH 6.1. The structural differences are
      small, indicating that C2-I does not unfold, even at a pH value as low as 3.0.
      The ADP-ribosyl transferase activity of C2-I was determined for alpha and
      beta/gamma-actin and related to that of Iota toxin and of mutant S361R of C2-I
      that introduced the arginine observed in Iota toxin. The substantial activity
      differences between alpha and beta/gamma-actin cannot be explained by the protein
      structures currently available. The structure of the transport component C2-II at
      pH 4.3 was established by molecular replacement using a model of the protective
      antigen of anthrax toxin at pH 6.0. The C-terminal receptor-binding domain of C2
      II could not be located but was present in the crystals. It may be mobile. The
      relative orientation and positions of the four other domains of C2-II do not
      differ much from those of the protective antigen, indicating that no large
      conformational changes occur between pH 4.3 and pH 6.0. A model of the C2-IIa
      prepore structure was constructed based on the corresponding assembly of the
      protective antigen. It revealed a surprisingly large number of asparagine
      residues lining the pore. The interaction between C2-I and C2-IIa and the
      translocation of C2-I into the target cell are discussed.

PMID- 17027032
TI  - Mixed macromolecular crowding accelerates the refolding of rabbit muscle creatine
      kinase: implications for protein folding in physiological environments.
AB  - The effects of four single macromolecular crowding agents, Ficoll 70, dextran 70,
      polyethylene glycol (PEG) 2000, and calf thymus DNA (CT DNA), and three mixed
      crowding agents containing both CT DNA and polysaccharide (or PEG 2000) on the
      refolding of guanidine hydrochloride-denatured rabbit muscle creatine kinase (MM
      CK) have been examined by activity assay. When the total concentration of the
      mixed crowding agent is 100 g/l, in which the weight ratio of CT DNA to Ficoll 70
      is 1:9, the refolding yield of MM-CK after refolding for 3 h under these
      conditions increases 23% compared with that in the presence of 10 g/l CT DNA, 18%
      compared with 100 g/l Ficoll 70, and 19% compared with that in the absence of
      crowding agents. A remarkable increase in the refolding yield of MM-CK by a mixed
      crowding agent containing CT DNA and dextran 70 (or PEG 2000) is also observed.
      Further folding kinetics analyses show that these three mixed crowding agents
      remarkably accelerate the refolding of MM-CK, compared with single crowding
      agents. Aggregation of MM-CK in the presence of any of the three mixed crowding
      agents is less serious than that in the presence of a single crowding agent at
      the same concentration but more serious than that in the absence of crowding
      agents. Both the refolding yield and the refolding rate of MM-CK in mixtures of
      these agents are increased relative to the individual agents by themselves,
      indicating that mixed macromolecular crowding agents are more favorable to MM-CK
      folding and can be used to reflect the physiological environment more accurately
      than single crowding agents.

PMID- 17027033
TI  - A mouse model of posttraumatic stress disorder that distinguishes between
      conditioned and sensitised fear.
AB  - The pathomechanisms of posttraumatic stress disorder (PTSD) are still unknown,
      but both fear conditioning and stress sensitisation are supposed to play a
      crucial role. Hence, valid animal models that model both associative and non
      associative components of fear will facilitate elucidation of the biological
      substrates of the illness, and to develop novel and specific approaches for its
      prevention and therapy. Here we applied a single electric footshock to C57BL/6N
      (B6N) and C57BL/6JOla (B6JOla) mice and recorded the conditioned response to
      contextual trauma reminders (associative fear), the sensitised reaction to a
      neutral tone in a novel environment (non-associative fear, hyperarousal), social
      interaction and various emotional behaviours using Modified Holeboard, Test for
      Novelty-Induced Suppression of Feeding and Forced Swimming Test, after different
      incubation times (1, 14, 28 days). Freezing generally increased as a function of
      shock intensity. In B6N mice, sensitised fear was maximal 28 days after trauma
      and was accompanied by signs of emotional blunting and social withdrawal. B6JOla
      mice, in contrast, were less susceptible to develop PTSD-like symptoms. The
      phenotype of B6N exhibited high behavioural variance, allowing distinction
      between vulnerable and resilient individuals. Only in vulnerable B6N mice,
      chronic fluoxetine treatment - initiated after an incubation period of 28 days -
      ameliorated sensitised fear. This new mouse model fulfils common criteria for
      face and predictive validity and can be used to investigate the biological
      correlates of individual fear susceptibility, as well as the impact and
      interrelationship of associative and non-associative fear components in the
      development and maintenance of PTSD.

PMID- 17027034
TI  - Cambodian founder effect for spinocerebellar ataxia type 3 (Machado-Joseph
      disease).
AB  - Four families from the same region of Cambodia immigrated to the Pacific
      Northwest of the United States. All four families have been discovered to have
      spinocerebellar ataxia type 3 (SCA 3; Machado-Joseph disease) with a similar
      clinical phenotype. CAG repeat expansions in the ATXN3 gene range from 72 to 77.
      Mean age of onset has varied from 19 to 44 years and mean age at death of 4
      individuals has been 60 years. The prevalence of the various subtypes of SCA
      varies worldwide from country to country. Neurologists should be alert to the
      possibility of SCA 3 in Cambodian patients with unexplained cerebellar ataxia.

PMID- 17027035
TI  - Intrafamilial phenotypic and genetic heterogeneity of dystonia.
AB  - Most cases of early-onset primary torsion dystonia are caused by the same 3-bp
      (GAG) deletion in the DYT1 gene. We describe a large Serbian family with
      significant intrafamilial variability of the DYT1 phenotype, from asymptomatic
      carrier status to late-onset focal, and generalized jerky dystonia. Seven
      mutation carriers (six proven by direct analysis and one by inferred haplotype)
      were identified, but only two of them were affected by dystonia (penetrance
      reduced to 29%). In addition, three GAG-deletion-negative family members also
      developed dystonia (two multifocal dystonia and one torticollis), suggesting that
      their involuntary movements are due to some other etiological factor(s) (i.e.,
      another dystonia gene), or may be psychogenic.

PMID- 17027036
TI  - Angiosperms (seagrass) within the EU water framework directive: a UK perspective.
AB  - Taxonomic composition, the presence of disturbance-sensitive species and
      abundance are attributes for monitoring the status of marine angiosperms; a
      biological quality element required for assessment of environmental condition
      under the Water Framework Directive (WFD). Their relevance for defining the
      ecological status of UK water bodies and the establishment of reference
      conditions for these attributes are described. Founded on quantitative
      measurements of these attributes, a set of metrics has been developed for
      monitoring and assessment of the only truly marine angiosperms, seagrass. The
      proposed metrics are presented and tested against a variety of littoral and
      sublittoral UK seagrass beds. In combination they express the cumulative response
      of marine angiosperms to different levels of anthropogenic disturbance.

PMID- 17027037
TI  - Survival under chronic stress from sediment load: spatial patterns of hard coral
      communities in the southern islands of Singapore.
AB  - Six reef sites were chosen along the west coast of the southern islands of
      Singapore, at an increasing distance from the densely populated metropolitan
      area, to study the spatial patterns of coral reef communities on the upper reef
      slope ( approximately 4m) and the associated environmental conditions. Chronic
      exposure to high sediment load was the most obvious form of anthropogenic stress.
      Recruitment rates on ceramic tiles were low (1.4+/-1.0-20+/-14.7 recruits m(-2)
      yr(-1)) but decreased towards the main island of Singapore as did hard coral
      cover and coral density. Coral fauna consisted of genera generally found in
      deeper waters (e.g., fungiids, foliose Oxypora, Leptoseris, and Echinopora) or
      those well-adapted to turbid waters (e.g., Porites, Pectinia, Leptastrea,
      Montipora). Light extinction coefficient (K) and % live coral cover (%LCC) showed
      a strong and inverse curvilinear relationship (%LCC=13.60 *K(-3.40)). Similarly,
      the rate of sediment deposition (DFSPM) (RR=1.51-0.17 *DFSPM) and water clarity
      (RR=3.56-2.92 *K) exhibited strong and inverse relationships with recruitment
      rates (RR). Although measured levels of the downward flux of suspended
      particulate matter and suspended solids were well within "normal" levels recorded
      in the literature, it was the proportion of benthic space, generic coral
      composition, and site history that offered compelling evidence of chronic
      exposure to increased sediment load. Clearly a reduction in both water clarity
      and live-coral cover has taken place since monitoring efforts began in the early
      1970s, in fact coral cover has more than halved at all sites examined since the
      1980s and benthic space was predominantly occupied by dead corals covered with
      sediment and filamentous algae.

PMID- 17027038
TI  - Globally attracting attenuant versus resonant cycles in periodic compensatory
      Leslie models.
AB  - We use a periodically forced density-dependent compensatory Leslie model to study
      the combined effects of environmental fluctuations and age-structure on pioneer
      populations. In constant environments, the models have globally attracting
      positive fixed points. However, with the advent of periodic forcing, the models
      have globally attracting cycles. We derive conditions under which the cycle is
      attenuant, resonant, and neither attenuant nor resonant. These results show that
      the response of age-structured populations to environmental fluctuations is a
      complex function of the compensatory mechanisms at different life-history stages,
      the fertile age classes and the period of the environment.

PMID- 17027039
TI  - A general bilinear model to describe growth or decline time profiles.
AB  - Linear models are widely used because of their unrivaled simplicity, but they
      cannot be applied for data that have a turning-or rate-change-point, even if the
      data show good linearity sufficiently far from this point. To describe such
      bilinear-type data, a completely generalized version of a linearized
      biexponential model (LinBiExp) is proposed here to make possible smooth and fully
      parametrizable transitions between two linear segments while still maintaining a
      clear connection with the linear models. Applications and brief conclusions are
      presented for various time profiles of biological and medical interest including
      growth profiles, such as those of human stature, agricultural crops and fruits,
      multicellular tumor spheroids, single fission yeast cells, or even labor
      productivity, and decline profiles, such as age-effects on cognition in patients
      who develop dementia and lactation yields in dairy cattle. In all these cases,
      quantitative model selection criteria such as the Akaike and the Schwartz
      Bayesian information criteria indicated the superiority of the bilinear model
      compared to adequate less parametrized alternatives such as linear, parabolic,
      exponential, or classical growth (e.g., logistic, Gompertz, Weibull, and
      Richards) models. LinBiExp provides a versatile and useful five-parameter
      bilinear functional form that is convenient to implement, is suitable for full
      optimization, and uses intuitive and easily interpretable parameters.

PMID- 17027040
TI  - Intracellular delay limits cyclic changes in gene expression.
AB  - Based on previously published experimental observations and mathematical models
      for Hes1, p53 and NF-kappaB gene expression, we improve these models through a
      distributed delay formulation of the time lag between transcription factor
      binding and mRNA production. This description of natural variability for delays
      introduces a transition from a stable steady state to limit cycle oscillations
      and then a second transition back to a stable steady state which has not been
      observed in previously published models. We demonstrate our approach for two
      models. The first model describes Hes1 autorepression with equations for Hes1
      mRNA production and Hes1 protein translation. The second model describes Hes1
      repression by the protein complex Gro/TLE1/Hes1, where Gro/TLE1 is activated by
      Hes1 phosphorylation. Finally, we discuss our analytical and numerical results in
      relation to experimental data.

PMID- 17027042
TI  - Differential noradrenergic influence on seizure expression in genetically Fast
      and Slow kindling rat strains during massed trial stimulation of the amygdala.
AB  - The involvement of alpha(2) noradrenergic receptors during amygdala 'massed'
      stimulation (MS) was examined in rats that were selectively bred to be seizure
      prone (Fast) or seizure-resistant (Slow) to amygdala kindling. The selective
      alpha(2) noradrenergic agonist guanfacine, or the antagonist idazoxan, was
      intraperitoneally injected during the MS procedure to study subsequent changes in
      afterdischarge (AD) threshold, AD duration and behavioral seizure expression.
      These measurements were again assessed weekly for 2 weeks after the MS treatment.
      Daily kindling began immediately thereafter. Following 6 stage-5 once daily
      convulsive seizures, guanfacine or idazoxan were re-administered. With idazoxan,
      the Slow rats expressed greater numbers of convulsive seizures and longer AD
      durations compared to guanfacine or saline controls during MS treatment. This pro
      convulsive property of idazoxan was absent in Fast rats. By contrast, Fast rats
      showed enhanced convulsive expression in the presence of guanfacine. In the fully
      kindled rat, idazoxan and guanfacine differentially impacted seizure duration and
      severity in the Slow rats, but again not in the Fast rats. These data suggest
      that some aspect(s) of the alpha(2) noradrenergic system in the Fast and Slow
      rats are dissimilar and the mechanisms by which these receptors govern seizure
      genesis and propagation may be genetically controlled and distinct.

PMID- 17027041
TI  - Neutrophil-activating activity and platelet-activating factor synthesis in
      cytokine-stimulated endothelial cells: reduced activity in growth-arrested cells.
AB  - The reactivity of endothelial cells (ECs) to proinflammatory cytokines is
      critically important for the pathogenesis of vascular diseases. Here, we studied
      functional alterations of human ECs during culture under a confluent condition;
      i.e., the alterations of neutrophil-activating activity, platelet-activating
      factor (PAF) synthesis, and granulocyte-macrophage colony-stimulating factor (GM
      CSF) production in cytokine-stimulated ECs. Human umbilical vein-derived ECs
      exhibited the increased activity in neutrophil activation, PAF synthesis, and GM
      CSF production when stimulated by proinflammatory cytokines such as interleukin-1
      beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The activity of
      cytokine-stimulated ECs to stimulate superoxide release in human neutrophils and
      to produce PAF declined markedly in parallel as ECs became growth-arrested during
      culture under a confluent condition. By contrast, GM-CSF production induced by
      cytokine stimulation was modestly increased, and up-regulation of intercellular
      adhesion molecule-1 (ICAM-1) and activation of mitogen-activated protein kinases
      were not altered. The neutrophil-activating activity of cytokine-stimulated ECs
      was dependent on PAF synthesis and GM-CSF production from ECs. These findings
      indicate that the reduced neutrophil-activating activity in growth-arrested ECs
      may be, at least in part, ascribed to down-regulation of PAF synthesis.

PMID- 17027043
TI  - Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in
      rat thalamus.
AB  - We have investigated the presence of histamine H(3) receptors (H(3)Rs) on rat
      thalamic isolated nerve terminals (synaptosomes) and the effect of their
      activation on glutamate and GABA release. N-alpha-[methyl-(3)H]histamine ([(3)H]
      NMHA) bound specifically to synaptosomal membranes with dissociation constant
      (K(d)) 0.78+/-0.20 nM and maximum binding (B(max)) 141+/-12fmol/mg protein.
      Inhibition of [(3)H]-NMHA binding by histamine and the H(3)R agonist immepip fit
      better to a two-site model, whereas for the H(3)R antagonist clobenpropit the
      best fit was to the one-site model. GTPgammaS (30 microM) decreased [(3)H]-NMHA
      binding by 55+/-4% and made the histamine inhibition fit better to the one-site
      model. Immepip (30 nM) induced a modest, but significant increase (113+/-2% of
      basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect
      prevented by clobenpropit (1 microM) and by pre-treatment with pertussis toxin.
      In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate
      release was inhibited by histamine (1 microM, 25+/-4% inhibition) and immepip (30
      nM, 38+/-5% reduction). These effects were reversed by clobenpropit (1microM).
      Conversely, immepip (up to 1 microM) had no effect on depolarisation-evoked
      [(3)H]-GABA release. Extracellular synaptic responses were recorded in the
      thalamus ventrobasal complex by stimulating corticothalamic afferents. H(3)R
      activation reduced by 38+/-7% the glutamate receptor-mediated field potentials
      (FPs), but increased the FP2/FP1 ratio (from 0.86+/-0.03 to 1.38+/-0.05) in a
      paired-pulse paradigm. Taken together, our results confirm the presence of H(3)Rs
      on thalamic nerve terminals and show that their activation modulates pre
      synaptically glutamatergic, but not GABAergic neurotransmission.

PMID- 17027044
TI  - Anticonvulsive effects of carbenoxolone on penicillin-induced epileptiform
      activity: an in vivo study.
AB  - Epilepsy is an important problem in neurological disorders. Recent studies
      claimed that gap junctions have a critical role in epileptic neuronal events. The
      aim of present study is to investigate the effects of gap junction blocker
      carbenoxolone on penicillin-induced experimental epilepsy. For this purpose, 4
      month-old male Wistar rats were used in the present study. Permanent screw
      electrodes allowing EEG monitoring from conscious animals and permanent cannula
      providing the administration of the substances to the brain ventricle were placed
      into the cranium of rats under general anesthesia. At the end of the
      postoperative recovery period, epileptiform activity was generated by injecting
      300 IU crystallized penicillin through the ventricular cannula. Epileptiform
      activity monitored from a digital recording system, when it reached its maximum
      intensity, carbenoxolone (100, 200, 500 nmol) was applied in the same way with
      penicillin. Effects of carbenoxolone on epileptiform activity were assessed by
      both electrophysiological and behavioral analysis. Carbenoxolone suppressed
      epileptiform activity by decreasing the amplitude and frequency of epileptiform
      spikes and by attenuating the epileptiform behavior. The results of this study
      suggest that the blockade of electrical synapses may contribute to the prevention
      and amelioration of epileptic activity.

PMID- 17027045
TI  - The effect of L-stepholidine, a novel extract of Chinese herb, on the
      acquisition, expression, maintenance, and re-acquisition of morphine conditioned
      place preference in rats.
AB  - The effect of L-stepholidine (SPD), a novel alkaloid extract of the Chinese herb
      Stephania with partial dopamine D1 receptor agonistic and D2 receptor
      antagonistic dual actions, on morphine conditioned place preference (CPP) was
      studied. Daily injection of morphine (10 mg/kg, i.p.) for 6 days induced CPP in
      rats, and daily treatment with SPD at 10 or 20 mg/kg before morphine injection
      dose-dependently attenuated morphine-induced CPP. On the day following
      acquisition of morphine CPP, a single administration of SPD at 10 or 20 mg/kg
      failed to block the expression of CPP. However, daily administration of SPD at 20
      mg/kg for 7 days attenuated the maintenance of CPP. Morphine-induced CPP
      extinguished after a 21-day saline training and then a single injection of
      morphine (3 mg/kg, i.p.) induced re-acquisition of morphine CPP; however,
      pretreatment with SPD at 10 or 20 mg/kg 30 min before morphine injection dose
      dependently blocked morphine (3 mg/kg, i.p.)-induced re-acquisition of morphine
      CPP. Furthermore, our data indicate that SPD had no effect on food-induced CPP or
      state-dependent learning, suggesting that the observed effect of SPD does not
      result from an inhibition of general learning ability. These results demonstrate
      that SPD can inhibit acquisition, maintenance, and re-acquisition of morphine
      conditioned place preference and suggest its potential for treatment of opioid
      addiction.

PMID- 17027046
TI  - Evidence for adenosine- and serotonin-mediated antihyperalgesic effects of
      cizolirtine in rats suffering from diabetic neuropathy.
AB  - Cizolirtine is a novel non-opioid drug which demonstrated antinociceptive
      activity in numerous pain models in rodents. Yet, its mechanism of action remains
      unknown. Several lines of evidence support the idea that adenosine (ADO) and
      serotonin (5-HT) modulate nociceptive signaling. Our study aimed at investigating
      whether these neuroactive molecules could be implicated in the mechanism of
      action of cizolirtine. Cizolirtine-induced antihyperalgesia was compared before
      and after pretreatment with ADO A(1)-A(2A) and 5-HT(1B/1D) receptor ligands in
      rats rendered diabetic by streptozotocin pretreatment and suffering from
      neuropathic pain. Cizolirtine alone (30-80 mg/kg, i.p.) significantly increased
      mechanical nociceptive thresholds. Acute pretreatment with the A(1)-A(2A)
      receptor antagonist caffeine (5 mg/kg, i.p.) or the 5-HT(1B/1D) receptor
      antagonist GR-127,935 (3 mg/kg, i.p.) significantly reduced the antihyperalgesic
      effects of cizolirtine. Conversely, cizolirtine-induced antihyperalgesia was
      promoted by pretreatment with either the selective A(1) receptor agonist CPA (0.3
      mg/kg, i.p.) or the selective 5-HT(1B) receptor agonist CP-94,253 (3mg/kg, i.p.),
      and this potentiation was totally prevented by acute pretreatment with respective
      antagonists. Interestingly, A(1) receptor blockade by DPCPX inhibited the
      promoting effect of CP-94,253 on cizolirtine-induced antihyperalgesia, suggesting
      that the adenosine A(1)-mediated step takes place downstream the serotonin 5
      HT(1B)-mediated step in the neurobiological mechanisms underlying cizolirtine
      action.

PMID- 17027047
TI  - ATP depletion does not account for apoptosis induced by inhibition of
      mitochondrial electron transport chain in human dopaminergic cells.
AB  - As the mitochondrial electron transport chain (ETC) is necessary for life, its
      inhibition results in cell death. To date, ETC complex (I-IV) inhibitors (ETCIs)
      have been thought to induce ATP depletion, triggering cellular apoptosis. To
      clarify whether the depletion of intracellular ATP is relevant to apoptosis
      induced by ETCIs, we conducted comparative studies using oxidative
      phosphorylation inhibitors (OPIs), including a specific F(0)F(1)ATP synthase
      inhibitor oligomycin, an ionophore valinomycin and an uncoupler 2,4
      dinitrophenol, as tools to deplete only ATP without influencing the ETC. In human
      dopaminergic SH-SY5Y cells, ETCIs (rotenone, thenoyltrifluoroacetone, antimycin A
      and potassium cyanide) depleted ATP and induced apoptosis. However, OPIs failed
      to induce apoptosis despite ATP being decreased to an extent comparable to that
      observed with ETCIs. Reactive oxygen species (ROS) production was augmented by
      ETCIs, but not by OPIs. Furthermore, ETCI-induced apoptosis was inhibited by the
      addition of an antioxidant N-acetylcysteine. Apoptosis was induced without ATP
      depletion by H(2)O(2) at a concentration that generated ROS at an amount
      comparable to that induced by ETCIs. Our findings demonstrate that ROS production
      is more relevant than ATP depletion to apoptosis induced by ETCIs.

PMID- 17027048
TI  - The "hidden" semantic category dissociation in mild-moderate Alzheimer's disease
      patients.
AB  - In patients manifesting mild-moderate Alzheimer's disease (AD), lexical semantic
      tasks are known to be influenced by several variables which should be adequately
      taken into account when studying semantic category dissociations. The following
      study provides indexes of three new variables (imageability (I), percentage of
      name agreement (pNA) and number of target alternatives (nTA)) and investigates
      their role in naming in a group of people with AD and in matched older adults
      controls. Forty young healthy participants rated I, pNA and nTA of 155 stimuli
      (including living and non-living items) from and sets. Forty-eight people with
      mild-moderate AD and 40 older adults were given the two naming tests and their
      naming ratings were analysed with a two-way ANOVA (two groupsxtwo categories) to
      assess category specificity and the effect of interaction. The influence of
      relevant concomitant variables in naming was measured using a multiple regression
      analysis. Semi-partial correlations were carried out to assess the independent
      contribution of each variable to naming. We found that living items were more
      imageable and had fewer lexical alternatives and higher name agreement than non
      living items. We also found that controls significantly named better than AD
      patients (F=37.551, p<.001), whilst the two-way ANOVA showed no significant
      effect of category (F=.649, p=.423). Notably category effect emerged when
      assessing its independent contribution performing a semi-partial correlation
      (beta=-.278, p<.001) which kept the effect of relevant concomitant variables
      under control. Our results confirm that category dissociation does emerge in mild
      moderate AD patients when the effect of relevant concomitant variables is
      adequately taken into account. The hypothesis that the highly correlated
      properties of items from biological categories may play a protective effect on
      living things, making them less prone to impairment in the early stages of AD, is
      discussed.

PMID- 17027049
TI  - Stimulus animal characteristics do not modulate the expression of partner
      preference by female rats.
AB  - The stimulus animals used in tests of partner preference in female rats vary. To
      test the hypothesis that the alternative stimulus animal modulates the preference
      for an intact male, gonadectomized (GDX) female rats received estradiol benzoate
      plus progesterone or the oil vehicle and were tested for partner preference with
      either an intact male paired with a GDX hormone-primed female or an intact male
      paired with a GDX male. Rats were tested under conditions that limited physical
      contact (No Contact) or allowed sexual interaction (Contact). Stimulus animal
      condition was not a primary determinant of partner preference. In contrast,
      contact condition and hormone treatment modulated preference, as well as activity
      levels and the display of proceptive behaviors. Our findings demonstrate that the
      characteristics of the alternative stimulus animals tested here do not play a
      significant role in modulating partner preference in female rats.

PMID- 17027050
TI  - Heat and social rank impact behavior and physiology of PRRS-virus-infected pigs.
AB  - Changes in thermal environment can invoke a stress response in pigs, which in
      turn can potentially impact their immune system and disease susceptibility. We
      investigated effects of heat stress and social rank on behavior, immune
      responsiveness, and performance of pigs challenged with porcine reproductive and
      respiratory syndrome (PRRS) virus. Sixty-four 7-week-old PRRS-naive pigs were
      assigned to each of four experimental treatments consisting of a 2 x 2 factorial
      design: PRRS (PRRS- or PRRS+) and environmental temperature (24 degrees C or 32
      degrees C). Blood samples were taken prior to and at days 7 and 14 post
      inoculation, and alveolar macrophages were collected via bronchoalveolar lavage
      at day 14. Total white blood cell counts, natural killer cytotoxicity, macrophage
      numbers, macrophage subpopulations, and performance measures were all
      significantly affected by social rank, heat stress, and/or infection status of
      the pig. Heat stress and PRRS status also significantly influenced the amount of
      time pigs spent lying with or without contacting another animal. Cortisol and
      various immune measures were also affected by PRRS status. These results show not
      only that intranasal inoculation with PRRS virus affects physiological,
      behavioral, and performance measures in growing pigs, but that social rank
      influences pigs' immune responsiveness to PRRS as well. Moreover, heat stress
      does not have additive negative impact on physiological or performance traits in
      pigs challenged with PRRS virus.

PMID- 17027051
TI  - Are we getting what we pay for?
AB  - The British NHS delivers health care free at the point of access to whomever
      needs it. It is often claimed to be the envy of the world. But does it deliver
      health? Or could the resource put into the health service be better spent
      elsewhere? In this article, we discuss the determinants of health in the United
      Kingdom in the past, the rise of public health and the impact medical technology
      has had on health. We discuss resource distribution in health care, and apply the
      principles of health economics to the wider context of the delivery of health,
      rather than health care. With a background of rising demand for health care and
      rationing of resources in the UK, combined with inequalities in life expectancy
      related to position in society, we conclude that wealth redistribution,
      environmental regulation, improved nutrition and better education must come first
      in the priorities for achieving a healthy population.

PMID- 17027052
TI  - The contribution of health to the economy in the European Union.
AB  - Despite increasing recognition of the link between health and economic
      development in low-income countries, the relationship has to date received scant
      attention in rich countries. We argue that this lack of attention is not
      justifiable. While the economic argument for investing in health in rich
      countries may differ in detail from that in low-income countries, there is
      considerable and convincing evidence that significant economic benefits can be
      achieved by improving health not only in poor, but also in rich countries. Better
      health increases labour supply and productivity and historically, health has been
      a major contributor to economic growth. In spite of remaining evidence gaps
      economic policy-makers also in developed countries should consider investing in
      health as one (of few) ways by which to achieve their economic objectives.

PMID- 17027053
TI  - When the boat comes in.

PMID- 17027054
TI  - Age-related changes in hookworm infection, anaemia and iron deficiency in an area
      of high Necator americanus hookworm transmission in south-eastern Brazil.
AB  - Surprisingly few detailed age-stratified data exist on the epidemiology of
      hookworm and iron status, especially in Latin America. We present data from a
      cross-sectional survey examining 1332 individuals aged 0-86 years from a
      community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty
      eight percent of individuals were infected with the human hookworm Necator
      americanus. The force of infection (lambda=0.354) was similar to estimates from
      other areas of high hookworm transmission. Individuals from poorer households had
      significantly higher prevalence and intensity of infection than individuals from
      better-off households. The prevalence of anaemia, iron deficiency and iron
      deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most
      prevalent among young children and the elderly. Univariate analysis showed that
      haemoglobin and serum ferritin were both significantly negatively associated with
      hookworm intensity among both school-aged children and adults. Multivariate
      analysis showed that, after controlling for socio-economic status, iron
      indicators were significantly associated with heavy hookworm infection. Our
      results indicate that, even in areas where there is a low overall prevalence of
      anaemia, hookworm can still have an important impact on host iron status,
      especially in school-aged children and the elderly.

PMID- 17027055
TI  - Estrogenic activity of UV filter mixtures.
AB  - UV-absorbing chemicals (UV filters) are widely used for protection against UV
      radiation in sunscreens and in a variety of cosmetic products and materials.
      Depending on the breadth and factor of UV protection, they are added as single
      compounds or as a combination thereof. Some UV filters have estrogenic activity,
      but their activity and interactions in mixtures are largely unknown. In this
      work, we analyzed 8 commonly used UV filters, which are pure or partial hERalpha
      agonists, for their estrogenic activity in equieffective mixtures in a
      recombinant yeast assay carrying the human estrogen receptor alpha (hERalpha).
      Mixtures of two, four and eight UV filters alone, or in combination with 17 beta
      estradiol (E2), were assessed at different effect levels and no-observed-effect
      concentrations (NOEC). Predictions of the joint effects of these mixtures were
      calculated by employing the concentration addition (CA) and independent action
      (IA) model. Most binary mixtures comprising of pure hERalpha agonists showed a
      synergistic activity at all mixture combinations. Only in combination with
      benzophenone-1, antagonistic activity was observed at some effect levels. All
      mixtures of four or eight, pure or pure and partial hERalpha agonists, alone or
      including E2, showed synergistic activity at concentrations giving an increase of
      10% of basal activity (BC10). This occurred even at concentrations that were at
      the NOEC level of each single compound. Hence, there were substantial mixture
      effects even though each UV filter was present at its NOEC level. These results
      show that significant interactions occur in UV filter mixtures, which is
      important for the hazard and risk assessments of these personal care products.

PMID- 17027056
TI  - Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066
      1087) as the fusion peptide.
AB  - The La Crosse Virus (LACV) M segment encodes two glycoproteins (Gn and Gc), and
      plays a critical role in the neuropathogenesis of LACV infection as the primary
      determinant of neuroinvasion. A recent study from our group demonstrated that the
      region comprising the membrane proximal two-thirds of Gc, amino acids 860-1442,
      is critical in mediating LACV fusion and entry. Furthermore, computational
      analysis identified structural similarities between a portion of this region,
      amino acids 970-1350, and the E1 fusion protein of two alphaviruses: Sindbis
      virus and Semliki Forrest virus (SFV). Within the region 970-1350, a 22-amino
      acid hydrophobic segment (1066-1087) is predicted to correlate structurally with
      the fusion peptides of class II fusion proteins. We performed site-directed
      mutagenesis of key amino acids in this 22-amino acid segment and determined the
      functional consequences of these mutations on fusion and entry. Several mutations
      within this hydrophobic domain affected glycoprotein expression to some extent,
      but all mutations either shifted the pH threshold of fusion below that of the
      wild-type protein, reduced fusion efficiency, or abrogated cell-to-cell fusion
      and pseudotype entry altogether. These results, coupled with the aforementioned
      computational modeling, suggest that the LACV Gc functions as a class II fusion
      protein and support a role for the region Gc 1066-1087 as a fusion peptide.

PMID- 17027057
TI  - Impact of genetic changes to the CRPV genome and their application to the study
      of pathogenesis in vivo.
AB  - The cottontail rabbit papillomavirus (CRPV)/rabbit model has been used to study
      oncogenicity and immunogenicity of different antigens from the papillomavirus
      genome and has therefore served as a preclinical model for the development of
      preventive and therapeutic vaccines against papillomavirus infections. One unique
      property of the CRPV model is that infection can be initiated using viral DNA.
      This property allows for the functional testing of viral mutants in vivo. We have
      introduced point mutations, insertions and deletions into all of the different
      coding and non-coding regions of the CRPV genome and have tested their
      infectivity in this model. We found that the majority of the mutant genomes
      retained viability and could induce papillomas in domestic rabbits. These data
      indicated that the CRPV genome is tolerant of many modifications without
      compromising its ability to initiate skin papillomas. In combination with our
      recently established HLA-A2.1 transgenic rabbit model, this plasticity allows us
      to extend the utility of the CRPV/rabbit model to the screening of HLA-A2.1
      restricted epitopes from other human viral and tumor antigens.

PMID- 17027059
TI  - Intracellular localization of varicella-zoster virus ORF39 protein and its
      functional relationship to glycoprotein K.
AB  - Varicella-zoster virus (VZV) encodes two multiply inserted membrane proteins,
      open reading frame (ORF) 39 protein (ORF39p) and glycoprotein K (gK). The HSV-1
      homologs of these proteins are believed to act in conjunction with each other
      during viral egress and cell-cell fusion, and they directly influence each
      other's intracellular trafficking. However, ORF39p and VZV gK have received very
      limited study largely due to difficulties in producing antibodies to these highly
      hydrophobic proteins. To overcome this obstacle, we introduced epitope tags into
      both ORF39p and gK and examined their intracellular distributions in transfected
      and infected cells. Our data demonstrate that both ORF39p and gK accumulate
      predominately in the ER of cultured cells when expressed in the absence of other
      VZV proteins or when coexpressed in isolation from other VZV proteins. Therefore,
      the transport of VZV ORF39p and gK does not exhibit the functional
      interdependence seen in their HSV-1 homologs. However, during infection, the
      primary distributions of ORF39p and gK shift from the ER to the Golgi, and they
      are also found in the plasma membrane indicating that their intracellular
      trafficking during infection depends on other VZV-encoded proteins. During
      infection, ORF39p and gK tightly colocalize with VZV envelope glycoproteins B, E
      and H; however, the coexpression of ORF39p or gK with other individual viral
      glycoproteins is insufficient to alter the transport of either ORF39p or gK.

PMID- 17027058
TI  - Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that
      infect Chlorella NC64A.
AB  - Viruses NY-2A and AR158, members of the family Phycodnaviridae, genus
      Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like
      green alga, Chlorella NC64A. The 368,683-bp genome of NY-2A and the 344,690-bp
      genome of AR158 are the two largest chlorella virus genomes sequenced to date; NY
      2A contains 404 putative protein-encoding and 7 tRNA-encoding genes and AR158
      contains 360 putative protein-encoding and 6 tRNA-encoding genes. The protein
      encoding genes are almost evenly distributed on both strands, and intergenic
      space is minimal. Two of the NY-2A genes encode inteins, the large subunit of
      ribonucleotide reductase and a superfamily II helicase. These are the first
      inteins to be detected in the chlorella viruses. Approximately 40% of the viral
      gene products resemble entries in the public databases, including some that are
      unexpected for a virus. These include GDP-d-mannose dehydratase, fucose synthase,
      aspartate transcarbamylase, Ca(++) transporting ATPase and ubiquitin. Comparison
      of NY-2A and AR158 protein-encoding genes with the prototype chlorella virus PBCV
      1 indicates that 85% of the genes are present in all three viruses.

PMID- 17027060
TI  - Adenoviral infection induces a multi-faceted innate cellular immune response that
      is mediated by the toll-like receptor pathway in A549 cells.
AB  - Adenovirus vectors are known to induce certain genes and impact innate response
      networks, but a broad understanding of this process and its mechanisms is
      currently lacking. For this reason, we chose to investigate and characterize Ad
      innate immunity using homogeneous, primary MEF cells replete with all the
      elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an
      array-based approach to maximally define transcriptome changes induced upon Ad
      vector infection, we discovered that Ad infection induces a potent gene and
      transcription factor network response. This response is characterized by
      significant changes in the expression of genes involved in focal adhesion, tight
      junction, and RNA regulation, in addition to TLR pathway and other innate sensing
      genes. Further investigation using human A549 cells knocked down for various TLR
      pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and
      interferon responses, thus confirming TLR involvement in Ad-mediated immunity
      across diverse species.

PMID- 17027061
TI  - Age related differences in learning with the useful field of view.
AB  - In naturalistic tasks, subjects often interact with a cluttered visual
      environment in which they need to divide their attention simultaneously among
      multiple objects and tasks. Previous work examining the effects of aging in tasks
      that approximate these real world demands have shown that performance often
      declines with age. For example, when subjects must perform central and peripheral
      visual tasks simultaneously in a Useful Field of View (UFOV) task, performance on
      the peripheral task declines relative to when subjects perform the peripheral
      task alone, and this divided-attention deficit grows decade-by-decade throughout
      our lifetimes [e.g., Sekuler, A.B., Bennett, P.J., and Mamelak, M. (2000).
      Effects of Aging on the Useful Field of View. Experimental Aging Research, 26,
      103-120]. Here, we investigated the extent to which age-related differences in
      divided-attention could be overcome with practice. In addition, we assessed how
      divided attention costs varied when initial performance levels were equated
      across age groups at the start of practice. Experiment 1 determined the stimulus
      durations that approximately equated attentional costs for younger and older
      subjects. These stimulus durations were used in Experiments 2 and 3 to equate
      task difficulty across age. Experiments 2 and 3 examined the effect of practice
      for 1-2 weeks. Practice improved performance for both younger and older subjects,
      and, when older subjects were provided with enough practice, their attentional
      costs were equivalent to those of younger subjects. Indeed, with enough practice,
      both younger and older subjects reached a point where they showed no divided
      attention deficits, although older subjects may need more practice to reach this
      point. Finally, the beneficial effects of practice were maintained for at least
      three months.

PMID- 17027062
TI  - Contamination levels of selected organochlorine and organophosphate pesticides in
      the Selangor River, Malaysia between 2002 and 2003.
AB  - In Malaysia, rivers are the main source of public water supplies. This study was
      conducted from 2002 to 2003 to determine the levels of selected organochlorine
      and organophosphate pesticides in the Selangor River in Malaysia. Surface water
      samples have been collected seasonally from nine sites along the river. A liquid
      liquid extraction followed by gas chromatography-mass spectrometry technique was
      used to determine the trace levels of these pesticide residues. The
      organochlorine pesticides detected were lindane, heptachlor, endosulfan,
      dieldrin, endosulfan sulfate, o,p'-DDT, p,p'-DDT, o,p'-DDE and p,p'-DDE whereas
      for organophosphate pesticides, they were chlorpyrifos and diazinon. At the river
      upstream where a dam is located for public water supply, incidents of pesticide
      levels exceeding the European Economic Community Directive of water quality
      standards have occurred. Furthermore, the wetland ecosystems located at the
      downstream of the river which houses the fireflies community is being threatened
      by occasional pesticide levels above EPA limits for freshwater aquatic organisms.
      The occurrence of these residual pesticides in the Selangor River can be
      attributed to the intense agriculture and urban activity.

PMID- 17027063
TI  - Langerhans cell histiocytosis and its relationship with Epstein-Barr virus.

PMID- 17027064
TI  - Biogenic emissions of isoprenoids and NO in China and comparison to anthropogenic
      emissions.
AB  - In this study, a regional dynamical model (WRF) is used to drive biogenic
      emission models to calculate high resolution (10x10 km) biogenic emissions of
      isoprene (C(5)H(8)), monoterpenes (C(10)H(16)), and nitric oxide (NO) in China.
      This high resolution biogenic inventory will be available for the community to
      study the effect of biogenic emissions on photochemical oxidants in China. The
      biogenic emissions are compared to anthropogenic emissions to gain insight on the
      potential impact of the biogenic emissions on tropospheric chemistry, especially
      ozone production in this region. The results show that the biogenic emissions in
      China exhibit strongly diurnal, seasonal, and spatial variations. The isoprenoid
      (including both isoprene and monoterpenes) emissions are closely correlated to
      tree density and strongly vary with season and local time. During winter
      (January), the biogenic isoprenoid emissions are the lowest, resulting from lower
      temperature and solar radiation, and highest in summer (July) due to higher
      temperature and solar radiation. The biogenic NO emissions are also higher during
      summer and lower during winter, but the magnitude of the seasonal variation is
      smaller than the emissions of isoprene and monoterpenes. The biogenic emissions
      of NO are widely spread out in the northern, eastern, and southern China regions,
      where high-density agricultural soil lands are located. Both biogenic NO and
      isoprenoid emissions are very small in western China. The calculated total
      biogenic emission budget is smaller than the total anthropogenic VOC emission
      budget in China. The biogenic isoprenoid and anthropogenic VOC emissions are 10.9
      and 15.1 Tg year(-1), respectively. The total biogenic and anthropogenic
      emissions of NO are 5.9 and 11.5 Tg(NO) year(-1), respectively. The study shows
      that in central eastern China, the estimated biogenic emissions of isoprenoids
      are very small, and the anthropogenic emissions of VOCs are dominant in this
      region. However, in northeastern and southern China, there are relatively large
      biogenic emissions of isoprenoids, leading to an important impact on the ozone
      production in these regions. Furthermore, the emissions of isoprenoids are
      highest during summer and noontime, which correlates to the peak of ozone
      production period. For example, the ratio between summer and winter for the
      emissions of isoprenoids is about 15 in China. As a result, the biogenic
      emissions of isoprenoids are significantly larger than the anthropogenic
      emissions of VOCs in China during daytime in summer. Biogenic NO emissions are
      mostly produced by agricultural soils which co-exist with large populations and
      human activity. As a result, the biogenic emissions of NO are mostly overlapped
      with the anthropogenic emissions of NO, leading to the enhancement in NO
      concentrations in the high anthropogenic NO emission regions. Finally, the future
      emissions of isoprene and monoterpenes over China are estimated. The results show
      that the future biogenic emissions may increase significantly due to land cover
      changes in central eastern China, which could have a very important impact on
      ozone formation in this region. However, these estimates are highly uncertain and
      are presented as a potential scenario to show the importance of possible changes
      of biogenic emissions in China.

PMID- 17027065
TI  - EPCR gene A3 haplotype and elevated soluble endothelial protein C receptor
      (sEPCR) levels in Turkish pediatric stroke patients.
AB  - INTRODUCTION: High plasma levels of sEPCR lead to dysfunction of the EPCR
      mediated coagulation. We have evaluated the role of EPCR A3 haplotype with its
      representative promoter variant 1651 C-G in a total of twenty-seven pediatric
      stroke patients and fifty-nine healthy subjects. MATERIALS AND METHODS:
      Genotyping of the A3 haplotype was performed with RFLP analysis. Plasma sEPCR
      levels were measured with ELISA. The mutant 1651 G allele frequency was observed
      to be 0.166 in the patient group. Common risk factors such as FV 1691 G-A and PT
      20210 G-A mutations were also screened. RESULTS AND CONCLUSIONS: None of the
      patients with sEPCR levels below 100 ng/ml carried the A3 haplotype, while
      patients with elevated sEPCR levels carried the A3 haplotype either in a
      heterozygous or homozygous state. Our study confirms that there is a strong
      association between A3 haplotype and elevated sEPCR levels. We suggest that
      elevated sEPCR levels might increase the risk of stroke at pediatric age when
      compared to controls. Studies with large series of patients are warranted to
      confirm this hypothesis.

PMID- 17027066
TI  - Promise and problems of translational research.

PMID- 17027067
TI  - The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined
      to the labium majus or minus.
AB  - OBJECTIVE: To determine the pattern of lymph node metastases, recurrence rate,
      and survival of patients with lateral T1 and T2 squamous cell cancer (SCC) of the
      vulva treated by radical vulvectomy or hemivulvectomy and inguinal
      lymphadenectomy. METHODS: An institutional review was performed to identify
      lateral T1 and T2 SCC of the vulva confined to the labium majus and minus.
      RESULTS: Sixty-one patients with lateral T1 and 61 patients with lateral T2 SCC
      of the vulva were treated from 1963 to 2003. Radical vulvectomy (RV) was
      performed in 60 patients, and radical hemivulvectomy (RHV) in 62 patients. Seven
      of 61 patients (11%) with T1 lesions had ipsilateral superficial inguinal lymph
      node (SIL) metastases, but none had deep inguinal lymph (DIL) node metastases.
      Nineteen of 61 patients (31%) with T2 lesions had ipsilateral SIL metastases, and
      8 had ipsilateral DIL metastases. No patient had contralateral SIL or DIL
      metastases. Six patients (10%) with T1 lesions and seven patients (11%) with T2
      lesions developed recurrence to the ipsilateral vulva and were treated by re
      excision. All patients are alive with no evidence of disease 10-195 months after
      treatment. One patient with T1 and three patients with T2 SCC developed distant
      recurrence and died of disease (DOD) 10-15 months after surgery. Disease-free
      survival of patients with T1 lesions was 98% at 2 years and 98% at 5 years, and
      with T2 lesions was 95% at 2 years and 93% at 5 years. Local or distant
      recurrence was not more common in patients treated by RHV than in those treated
      by RV. CONCLUSION: Lateral T1 and T2 squamous cell cancers of the vulva spread to
      the ipsilateral inguinal lymph nodes and can be treated effectively with RHV and
      ipsilateral SIL dissection. Deep inguinal lymphadenectomy is indicated only when
      the SIL are positive.

PMID- 17027068
TI  - Summary and discussion of session recommendations.

PMID- 17027069
TI  - Biomarkers and clinical trial design.

PMID- 17027070
TI  - Potential predictors of chemotherapy response in ovarian cancer--how do we define
      chemosensitivity?
AB  - OBJECTIVE: The aim of this study was to assess whether microvessel density
      (measured by CD31), vascular endothelial growth factor (VEGF) or multidrug
      resistance (MDR1) could determine the response to chemotherapy or act as
      prognostic factors in ovarian cancer. METHODS: Seventy-nine ovarian specimens
      were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for
      univariate analysis. Kaplan Meier survival curves were used, log-rank was used
      for univariate analysis and a Cox proportional hazards regression model was used
      for multivariate evaluation. Response to chemotherapy was assessed after 6 months
      and again after 1 year. RESULT: Quantifying VEGF proved to be a valuable
      independent prognostic indicator in progression-free survival (PFS) (p<0.05) and
      overall survival (OS) (p<0.0001). VEGF correlated with response to chemotherapy
      at the 6-month interval (r=0.446, p<0.001) but failed to correlate at the 1-year
      interval. Increased staining with CD31 was associated with decreased PFS (p<0.01)
      and OS (p<0.01) in univariate but not multivariate analysis. MDR1 failed to act
      as a prognostic marker or as a predictor of response to chemotherapy. CONCLUSION:
      VEGF correlates with response to chemotherapy at the 6-month but not the 12-month
      interval. What should our criteria be for determining sensitivity to
      chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but
      other factors are likely to be involved and perhaps molecular profiling will
      determine which factors will be important for determining the response to
      chemotherapy.

PMID- 17027071
TI  - Expression of CD44, E-cadherin, and antimetastatic protein nm23-H1 in complete
      hydatidiform moles.
AB  - INTRODUCTION: There is scant information about the expression of CD44 and E
      cadherin, two cell adhesion molecules, and the antimetastatic protein nm23-H1, in
      complete hydatidiform moles. We measured the expression of these markers to
      determine their usefulness in predicting the development of invasive disease.
      MATERIALS AND METHODS: We performed a retrospective study of 27 patients with
      complete hydatidiform moles, collecting clinical information including the
      patient's age, pre-evacuation hCG level, pathology, hCG monitoring, and the
      development of gestational trophoblastic neoplasia. Immunohistochemical staining
      for CD44, E-cadherin, and nm23-H1 was performed. CD44 expression was classified
      as positive or negative. For E-cadherin and nm23-H1, the intensity of expression
      was graded on a 0 to 3 scale. Chi-square or Fisher's exact testing was used to
      evaluate the relationship between these markers and the development of invasive
      disease. RESULTS: CD44 was expressed in 26% of cases. E-cadherin expression was
      1+, 2+, and 3+in 8%, 33%, and 59% of cases, respectively. Nm23-H1 expression was
      1+, 2+, and 3+in 4%, 11%, and 85% of cases. The risk of developing invasive
      disease did not correlate with the expression of CD44, E-cadherin, or nm23-H1.
      CONCLUSION: In this preliminary study, there is no relationship between CD44, E
      cadherin, and nm23-H1 expression in complete hydatidiform moles and the risk of
      invasive disease. Other molecular markers predictive of invasive disease should
      be sought to limit hCG surveillance to those at risk.

PMID- 17027073
TI  - Intraperitoneal chemotherapy and the NCI clinical announcement.

PMID- 17027072
TI  - Long-term survival from gynecologic cancer: psychosocial outcomes, supportive
      care needs and positive outcomes.
AB  - OBJECTIVES: To assess the long-term psychosocial outcomes and supportive care
      needs of gynecologic cancer survivors. METHODS: Women who had received care in a
      tertiary-based gynecologic cancer center 1-8 years earlier and who were disease
      free were invited to complete a mailed self-report questionnaire to assess
      psychosocial outcomes and supportive care needs. RESULTS: In total, 199 survivors
      participated in the study. Survivors reported normal quality of life and
      relationship adjustment although functioning was at the lower end of the range;
      over two-thirds (68%) reported positive outcomes. However, nearly one-third (29%)
      reported clinical levels of anxiety and the most frequently endorsed need
      concerned fear of disease recurrence (24%). About one-fifth (19%) reported
      symptoms that indicated posttraumatic stress disorder (PTSD) and this rose to
      close to one-third (29%) for survivors of advanced stage disease. Nearly 90% of
      survivors reported supportive care needs and the diagnosis of anxiety or PTSD
      resulted in a four-fold increase in unmet needs. Needs most frequently concerned
      "existential survivorship" (e.g., spiritual beliefs, decision making, the meaning
      of life) and "comprehensive cancer care" (e.g., team care, communication, local
      health care services). Years since diagnosis was not related to distress or need
      levels. CONCLUSIONS: All members of the care team need to be aware that
      significant psychosocial morbidity may occur many years after the successful
      treatment of a gynecologic malignancy and may be associated with elevated
      supportive care needs. Comprehensive and extended supportive care services are
      required to address anxiety and trauma responses and investigate strategies to
      meet ongoing needs in order to improve long-term psychosocial outcomes.

PMID- 17027074
TI  - The future of phase II trials.

PMID- 17027075
TI  - The association between exposure to environmental tobacco smoke and breast
      cancer: a review by the California Environmental Protection Agency.
AB  - BACKGROUND: The California Environmental Protection Agency (Cal/EPA) recently
      completed a health effects assessment of exposure to environmental tobacco smoke
      (ETS) which resulted in California listing ETS as a Toxic Air Contaminant in
      January 2006. As part of the assessment, studies on the association between
      exposure to ETS and breast cancer were reviewed. METHODS: Twenty-six published
      reports (including 3 meta-analyses) evaluating the association between ETS
      exposure and breast cancer were reviewed. A weight-of-evidence approach was
      applied to evaluate the data and draw conclusions about the association between
      breast cancer and ETS exposure. RESULTS: The published data indicate an
      association between ETS and breast cancer in younger primarily premenopausal
      women. Thirteen of 14 studies (10 case-control and four cohort) that allowed
      analysis by menopausal status reported elevated risk estimates for breast cancer
      in premenopausal women, seven of which were statistically significant. Our meta
      analyses indicated elevated summary relative risks ranging from OR 1.68 (95% C.I.
      1.31, 2.15) for all 14 studies to 2.20 (95% C.I. 1.69, 2.87) for those with the
      best exposure assessment. CONCLUSIONS: Cal/EPA concluded that regular ETS
      exposure is causally related to breast cancer diagnosed in younger, primarily
      premenopausal women and that the association is not likely explained by bias or
      confounding.

PMID- 17027076
TI  - Involvement of Ca2+-dependent proteasome in the degradation of both cyclin B1 and
      Mos during spontaneous activation of matured rat oocytes.
AB  - In matured rat oocytes, spontaneous activation from the metaphase-II (MII) stage
      occurred after collection from the oviducts. It is well known that the mitogen
      activated protein kinase (MAPK) pathway and p34(cdc2) kinase play an important
      role in the arrest at MII in other species. However, there is no information
      about the difference in these factors among strains of rats. In the present
      study, in spontaneously activated oocytes from the Wistar rat, the Mos protein
      level and the activity of MAPK kinase (MEK)/MAPK were decreased at 120 min (13.8,
      25.7, and 19.3, respectively, P<0.05), whereas Sprague-Dawley (SD) oocytes, which
      were not spontaneously activated, had a high level of Mos protein and MEK/MAPK
      activity (75.9, 76.2, and 87.9, respectively, P<0.05). Phosphorylation of MAPK in
      the SD oocytes was significantly suppressed by MEK inhibitor, U0126 at 60 min;
      this treatment decreased p34(cdc2) kinase activity via cyclin B1 degradation in a
      time-dependent manner. The treatment with proteasome inhibitor, MG132 or Ca2+
      chelator, BAPTA-AM, overcame the spontaneous degradation of both Mos and cyclin
      B1 in a dose-dependent manner in Wistar oocytes. More than 90% of Wistar oocytes
      treated with BAPTA-AM were arrested at MII until 120 min. In conclusion, SD
      oocytes carrying Mos/MEK/MAPK, maintained a high activity of p34(cdc2) kinase by
      stabilizing cyclin B1, thus involved in their meiotic arrest. In contrast, Wistar
      oocytes had a relatively low cytostatic factor activity; rapid decrease of
      Mos/MEK/MAPK failed to stabilize both cyclin B1 and Mos, and these oocytes were
      likely to spontaneously activate.

PMID- 17027077
TI  - Evaluation of artificial chaperoning behavior of an insoluble cyclodextrin-rich
      copolymer: solid-phase assisted refolding of carbonic anhydrase.
AB  - Insoluble beta-cyclodextrin (beta-CD) copolymers have been used for the refolding
      of thermally and/or chemically denatured carbonic anhydrase with refolding yield
      of 40% using 300 mg of the copolymer/ml refolding solution containing 0.042 mg/ml
      protein. In an attempt to enhance the refolding yield with lower quantities of
      the copolymer, a new beta-CD-rich copolymer with higher beta-CD content was
      synthesized. Regarding the need for rapid stripping of the detergent molecules
      from the detergent-protein complexes formed in the capture step of the technique
      (artificial chaperone-assisted refolding), experimental variables (e.g. copolymer
      and the protein contents) were optimized to improve the refolding yields along
      with depressing the aggregate formation. In addition, comparative studies using
      different ionic detergents and the copolymer were conducted to get a more
      comprehensive understanding of the detergent's tail length in the stripping step
      of the process. Our results indicated that under the optimal developed refolding
      environment, the denatured CA was refolded with a yield of 75% using only 5mg of
      the copolymer/1.2 ml refolding solution containing 0.0286 mg/ml protein. Taking
      into account the recycling potential of the copolymer, the new resin, with
      significant cost-cutting capability, is a suitable candidate for industrial
      applications.

PMID- 17027078
TI  - Expression and cellular localisation of chloride intracellular channel 3 in human
      placenta and fetal membranes.
AB  - Chloride channels regulate the movement of a major cellular anion and are
      involved in fundamental processes that are critical for cell viability.
      Regulation of intracellular chloride is achieved by multiple classes of channel
      proteins. One class of putative channels are the chloride intracellular channel
      (CLIC) family. Evidence suggests that several CLICs are expressed in human
      placenta, although their roles in this tissue are not certain. Northern blot
      analysis has shown that CLIC3 is highly expressed in placenta relative to other
      human tissues; however, its cellular distribution is not known. This study used
      microarray expression profiling to clarify which CLICs are expressed in human
      placenta and RT-PCR, Western blot and immunohistochemistry to determine the
      expression pattern of CLIC3 in human placenta and fetal membranes. Placentas and
      fetal membranes were obtained from term pregnancies after delivery and placental
      tissue was obtained from first trimester following either chorionic villous
      sampling or elective pregnancy termination. Trophoblast cells were isolated from
      first trimester and term placentas and placental endothelial cells were isolated
      from term placentas. Microarray expression profiling identified high expression
      of mRNA for CLICs 1, 3 and 4 in the isolated first trimester and term trophoblast
      cells. High mRNA expression in the isolated endothelial cells was also found for
      CLICs 1 and 4, but not CLIC3. Low expression was found for CLIC5 in all three
      types of isolated cells. RT-PCR confirmed that CLIC3 mRNA was expressed in
      trophoblast cells at both gestational ages, but was not present in endothelial
      cells. CLIC3 mRNA was also identified in whole placental extracts at both
      gestational ages and in term amnion and choriodecidua. Immunohistochemistry using
      a chicken anti-human CLIC3 antibody localised strong CLIC3-specific staining to
      the syncytiotrophoblast and villous cytotrophoblast cells in both first trimester
      and term placentas, and weaker staining in extravillous trophoblast cells in
      first trimester. In fetal membranes at term strong CLIC3-specific staining was
      localised to chorionic trophoblast cells, with weaker staining in amniotic
      epithelial and decidual cells. It was previously shown that chloride uptake was
      increased into cells that had been transfected with CLIC3. CLIC3 may facilitate
      chloride ion movement and the regulation of cellular processes associated with
      the movement of chloride in the placental and fetal membrane cells in which it is
      expressed.

PMID- 17027079
TI  - Glucose transporter 1 localisation throughout pregnancy in the carnivore
      placenta: light and electron microscope studies.
AB  - Glucose is one of the major fetal nutrients. Maternofetal transfer requires
      transport across the several placental membranes. This transfer is mediated by
      one or more of the fourteen known isoforms of glucose transporter. So far only
      Glucose Transporters 1 and 3 (GT1, GT3) have been shown to be located in
      placental membranes. GT1 may be the only one on the syncytiotrophoblast (human)
      or both may be present on the same membrane (rodents) or be required in sequence
      (ruminants, horses and elephant). This paper shows GT1 to be the only transporter
      demonstrable by immunocytochemistry in carnivore (cat, dog and mink)
      endotheliochorial placental membranes. GT1 is invariably present on both apical
      and basal surfaces of the cyto- and syncytiotrophoblast in all carnivore species
      examined and the pattern of development is described from implantation to term.

PMID- 17027080
TI  - Calcium microdomains and the fine control of cell function: an introduction.

PMID- 17027081
TI  - Ca2+-sparks constitute elementary building blocks for global Ca2+-signals in
      myocytes of retinal arterioles.
AB  - Spontaneous Ca2+-events were imaged in myocytes within intact retinal arterioles
      (diameter <40 microm) freshly isolated from rat eyes. Ca2+-sparks were often
      observed to spread across the width of these small cells, and could summate to
      produce prolonged Ca2+-oscillations and contraction. Application of cyclopiazonic
      acid (20 microM) transiently increased spark frequency and oscillation amplitude,
      but inhibited both sparks and oscillations within 60s. Both ryanodine (100
      microM) and tetracaine (100 microM) reduced the frequency of sparks and
      oscillations, while tetracaine also reduced oscillation amplitude. None of these
      interventions affected spark amplitude. Nifedipine, which blocks store filling
      independently of any action on L-type Ca2+-channels in these cells, reduced the
      frequency and amplitude of both sparks and oscillations. Removal of external
      [Ca2+] (1mM EGTA) also reduced the frequency of sparks and oscillations but these
      reductions were slower in onset than those in the presence of tetracaine or
      cyclopiazonic acid. Cyclopiazonic acid, nifedipine and low external [Ca2+] all
      reduced SR loading, as indicated by the amplitude of caffeine evoked Ca2+
      transients. This study demonstrates for the first time that spontaneous Ca2+
      events in small arterioles of the eye result from activation of ryanodine
      receptors in the SR and suggests that this activation is not tightly coupled to
      Ca2+-influx. The data also supports a model in which Ca2+-sparks act as building
      blocks for more prolonged, global Ca2+-signals.

PMID- 17027082
TI  - The role of depression and dissociation in the relationship between childhood
      trauma and bulimic symptoms among ethnically diverse female undergraduates.
AB  - OBJECTIVE: The goals of this study were to examine the role of dissociation and
      depression as possible mediators of the relationship between several forms of
      childhood trauma and bulimic symptomatology and to explore potential ethnic
      differences in these relationships. METHOD: Four hundred seventeen female
      undergraduates participated in this cross-sectional study. They completed
      measures of dissociative, depressive, and bulimic symptoms, and childhood trauma.
      Experiences of multiple forms of childhood trauma were measured, including
      physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional
      neglect. However, only emotional abuse was correlated with bulimic symptoms at
      p<.01. Therefore, other forms of trauma were excluded from the analyses to
      control for Type I error. RESULTS: Dissociation was not associated with emotional
      abuse after controlling for depression; therefore, tests of dissociation as a
      mediator were discontinued. Depression was significantly associated with
      emotional abuse after controlling for dissociation. Emotional abuse was
      significantly associated with bulimia. Finally, emotional abuse and depression
      together were significantly associated with bulimia after controlling for
      dissociation. However, emotional abuse became nonsignificant when entered with
      depression, indicating that depression mediated the relationship between
      emotional abuse and bulimic symptoms. There were no ethnic differences in this
      relationship. CONCLUSIONS: It appears that among women who have experienced
      childhood emotional abuse, depression is more strongly associated with unhealthy
      eating behaviors than is dissociation. Results also suggest that emotional abuse
      is a form of childhood trauma particularly relevant to bulimia.

PMID- 17027083
TI  - Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome.
AB  - Mutations in complement regulatory proteins predispose to the development of
      aHUS. Approximately 50% of patients bear a mutation in one of three complement
      control proteins, factor H, factor I, or membrane cofactor protein (MCP; CD46).
      Another membrane regulator that is closely related to MCP, decay accelerating
      factor (DAF; CD55) thus far has shown no association with aHUS and continues to
      be investigated. The goal of this study was to compare the regulatory profile of
      MCP and DAF and to assess how alterations in MCP predispose to complement
      dysregulation. We employed a model system of complement activation on Chinese
      hamster ovary (CHO) cell transfectants. The four regularly expressed isoforms of
      MCP and DAF inhibited C3b deposition by the alternative pathway. DAF, but not
      MCP, inhibited the classical pathway. Most patients with MCP-aHUS are
      heterozygous and express only 25-50% of the wild-type protein. We, therefore,
      analyzed the effect of reduced levels of wild-type MCP and found that cells with
      lowered expression levels were less efficient in inhibiting alternative pathway
      activation. Further, a dysfunctional MCP mutant, expressed at normal levels and
      identified in five patients with aHUS (S206P), failed to protect against C3b
      amplification on CHO cells, even if expression levels were increased 10-fold. Our
      results add new information relative to the necessity for appropriate expression
      levels of MCP and further implicate the alternative pathway in disease processes
      such as aHUS.

PMID- 17027084
TI  - Distinct role of IL-3 promoter and enhancer region in murine mast cells.
AB  - Crosslinking of Fcvarepsilon receptor on mast cells induces IL-3 gene expression
      with the concentration dependent of intracellular calcium, but its regulatory
      mechanism remains unclear. Here, we found that phorbol 12-myristate 13-acetate
      (PMA) alone did not induce IL-3 gene expression, but potentiated A23187-induced
      IL-3 gene expression. Interestingly, the A23187-induced IL-3 promoter activity
      was suppressed by PMA, but it was enhanced when IL-3 promoter contained enhancer
      region, a DH site. While IL-3 mRNA expression was increased by A23187 and PMA in
      a dose-dependent manner, the promoter activity appeared all or none in all doses
      of A23187 and PMA. IL-3 promoter region between -293 and -150bp was responsible
      for A23187-induced gene expression and PMA- or cyclosporin A (CsA)-mediated
      suppression. Taken together, IL-3 gene expression was primarily regulated at the
      transcriptional level, which was differentially controlled by a restricted
      promoter and enhancer region.

PMID- 17027085
TI  - Structure and biological properties of the copper(II) complex with the quinolone
      antibacterial drug N-propyl-norfloxacin and 2,2'-bipyridine.
AB  - The neutral mononuclear copper complex with the quinolone antibacterial drug N
      propyl-protected norfloxacin, Hpr-norfloxacin, in the presence of the nitrogen
      donor heterocyclic ligand 2,2'-bipyridine has been prepared and characterized.
      The crystal structure of (chloro)(2,2'-bipyridine)(pr-norfloxacinato)copper(II),
      1, has been determined and refined with X-ray crystallography. X-band electron
      paramagnetic resonance (=EPR) spectroscopy at liquid helium temperatures from
      powdered samples indicates the presence of dimeric units in consistency with the
      crystal structure. In aqueous solutions of 1 the EPR behavior indicates mixture
      of dimeric and monomeric species. The antimicrobial activity of the complex has
      been tested on three different microorganisms and the best inhibition
      (MIC=0.25mugmL(-1)) has been exhibited against Escherichia coli. The study of the
      interaction of the complex with calf-thymus DNA has been performed with diverse
      spectroscopic techniques and has shown that complex 1 is bound to calf-thymus DNA
      by the intercalative mode. Potential anticancer cytostatic and cytotoxic effects
      of complex 1 on human promyelocytic leukemia HL-60 and human chronic myelogenous
      leukemia K562 cell lines have been investigated. Complex 1 shows an increased
      antiproliferative and necrotic effect on both HL-60 and K562 human leukemia cells
      in comparison to the free pr-norfloxacin.

PMID- 17027086
TI  - Microbiologically confirmed meningoencephalitis due to Enterococcus avium: a
      first report.
AB  - We describe an 80-year-old lady with a meningoencephalitic illness followed by
      vertebral discitis. Enterococcus avium was cultured from her cerebrospinal fluid.
      No other pathogen was incriminated in her illness. The meningoencephalitic
      illness settled after 3 weeks of antimicrobials, but the vertebral discitis
      required longer therapy.

PMID- 17027087
TI  - Bipolar spectrum and drug addiction.

PMID- 17027088
TI  - Integrin alpha5 is involved in fibronectin-induced human extravillous trophoblast
      invasion.
AB  - To identify the molecules involved in human extravillous trophoblast (EVT)
      invasion, we raised murine mAbs that react with EVTs and obtained one mAb (CHL3)
      that inhibited invasion of a human choriocarcinoma-derived cell line, BeWo cells.
      The N-terminal 22 aminoacid sequence of the CHL3 antigen (150kDa) purified from
      placental tissue completely matched that of integrin alpha5, which is known to
      interact with fibronectin. Double immunohistochemical staining and flow cytometry
      confirmed the reactivity of CHL3 with integrin alpha5 and its expression on the
      surface of BeWo cells and human EVTs isolated from villous explant cultures. CHL3
      mAb inhibited the attachment of human EVTs and BeWo cells to fibronectin-coated
      dishes, but not to Matrigel dishes. In the Matrigel invasion assay supplemented
      with or without fibronectin, the invasion of isolated EVTs and BeWo cells was
      attenuated by treatment with CHL3 without affecting cell proliferation. During
      invasion assays, the production of matrix metalloproteases 2 and 9 was not
      changed by CHL3. These findings suggest that interaction with fibronectin through
      integrin alpha5 plays an important role in human extravillous trophoblast
      invasion.

PMID- 17027089
TI  - Natural Killer T cells in patients with major depressive disorder.
AB  - CD56 (Natural Killer T) cells showed a significant negative correlation with
      depressive symptom scale scores in acute and unmedicated patients with major
      depressive disorder. Decreased CD56 cells may reflect the severity of depressive
      symptoms but not the severity of anxiety symptoms in major depression.

PMID- 17027090
TI  - Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic
      epithelial cells.
AB  - The gut maintains a delicate balance between the downregulation of inflammatory
      reactions to commensal bacteria and the capacity to respond to pathogens with
      vigorous cellular and humoral immune responses. Intestinal epithelial cells,
      including colonic epithelial cells (CECs) possess many properties of cells of the
      innate immune system, in particular the ability to recognize and respond to
      microbial antigens. Recognition of microorganisms by CECs is based upon their
      recognition of signature molecules, called microbe-associated molecular patterns
      (MAMP), by pattern recognition receptors (PRR) including membrane toll-like
      receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The
      purpose of this study was to determine whether primary CECs from normal dogs
      express a functional TLR2, TLR4, and Nod2 and whether they are regulated by
      inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and
      Nod2 that can be modulated in response to their respective MAMPs,
      lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate
      that these receptors are functional as evidenced by the induction of cytokine
      gene expression in response to LPS or PGN.

PMID- 17027092
TI  - Maternal IgG suppresses NMDA-induced spasms in infant rats and inhibits NMDA
      mediated neurotoxicity in hippocampal neurons.
AB  - Maternal immunoglobulin G (IgG) was derived from Wistar rats that just delivered
      the new offsprings. We examined the effect of this maternal IgG on infantile
      spasms induced by N-methyl-d-aspartate (NMDA) in immature rats. Pup animals were
      treated subcutaneously with 10 mg/kg/day maternal IgG from day 11 to day 15 after
      birth followed by a single intraperitoneal dose of NMDA (15 mg/kg).
      Administration of maternal IgG decreased the severity and increased the number of
      ACTH immunoreactive cells in the cortex of rats with NMDA-induced spasms.
      Furthermore, maternal IgG inhibited NMDA-induced intracellular LDH activity in
      cultured hippocampal neurons in a dose-dependent manner. The results indicate
      that maternal IgG can attenuate NMDA-induced seizures. In infantile spasms, some
      factors may during pregnancy negatively affect the transfer of maternal IgG from
      mother to fetus thereby causing a decrease in the amount of protective maternal
      IgG.

PMID- 17027091
TI  - The immune response to disialoganglioside GD3 vaccination in normal dogs: a
      melanoma surface antigen vaccine.
AB  - As a result of its metastatic potential, canine malignant melanoma like its human
      counterpart like its human counter part, has a poor response to conventional
      treatment protocols. This prompted us to investigate the possibility of enhancing
      the immune response against the melanoma cell surface antigen, disialoganglioside
      GD3. Initially a flow cytometric study was designed in which the incidence of GD3
      on the cell surface, recognized by the monoclonal antibody Mel-1 (R24), was
      established in canine melanoma cell lines. Results from the flow cytometry found
      GD3 to be highly expressed (94.2%) in six out of seven canine melanoma cell
      lines. Since it was thus potentially a good target, a study in which normal dogs
      were vaccinated intradermally with a vaccine containing GD3 plus adjuvants was
      designed. The adjuvant included CpG oligodeoxynucleotide (CpG-ODN) sequences and
      RIBI-adjuvant, which are known to target toll-like receptors (TLR) of the innate
      immune system. From a cohort of 10 dogs, 4 were vaccinated 3 times, at 4 weekly
      intervals with GD3 plus adjuvant, and 4 received only RIBI-adjuvant, and 2
      phosphate buffered saline. Caliper measurements were collected to assess skin
      reaction at the vaccination site and sera assayed for IgM and IgG antibodies
      against GD3 and cell-mediated cytotoxicity against a melanoma cell line. Results
      from the study found significant differences (P<0.05) in the vaccine site
      reactions, IgM/IgG levels and cell-mediated cytotoxicity in the vaccinated versus
      unvaccinated dogs. The addition of CpG-ODN sequences and increasing GD3
      concentration in the vaccine increased the inflammation response at the injection
      site. GD3 IgG and IgM antibodies in vaccinated dogs showed increasing titers over
      time and achieved significance at weeks 9 and 12, respectively. Cell-mediated
      cytotoxicity was only detected in peripheral blood mononuclear cells from
      vaccinated dogs. In conclusion, by combining the tumor antigen GD3 (a known weak
      self-antigen) and an adjuvant, tolerance was overcome by an innate and adaptive
      immune response in this population of normal dogs.

PMID- 17027093
TI  - Clozapine but not haloperidol treatment reverses sub-chronic phencyclidine
      induced disruption of conditional discrimination performance.
AB  - Abusers of phencyclidine (PCP) often present with a symptom profile similar to
      that exhibited by schizophrenic patients. Animal models utilising such
      psychotomimetics are currently informing research into the condition.
      Accumulating evidence suggests that a central cognitive deficit in schizophrenia
      is the inability to use task-setting cues to guide goal directed behaviour and
      that this ability is mediated by prefrontal dopamine (DA). The current study used
      the non-competitive NMDA antagonist phencyclidine (PCP) and Haloperidol (typical
      antipsychotic) and Clozapine (atypical antipsychotic) in order to further
      investigate the influence of DAergic manipulation on a task that requires the use
      of conditional information to inform goal-directed performance. An instrumental
      conditional discrimination task was employed in which rats learn to respond
      appropriately according to the presence of specific auditory conditional stimuli.
      Probe test 1 showed impaired conditional discrimination performance following sub
      chronic PCP administration (seven twice-daily injection protocol) compared to
      control which was reversed by acute treatment with clozapine (5 mg/kg) but not
      haloperidol (0.1 mg/kg) both administered 60 min pre-test. Probe test 2 (8 days
      post-treatment) showed enduring deficits to conditional discrimination
      performance that were again reversed by clozapine but not haloperidol (injection
      procedures as above). These results show that tasks dependent upon conditional
      relationships are particularly sensitive to manipulation of DAergic systems as
      prolonged treatment with PCP has been shown to selectively reduce prefrontal
      cortex (PFC) DA activity and treatment with clozapine (known to ameliorate
      cognitive deficits) but not haloperidol has been shown to selectively restore PFC
      DA levels.

PMID- 17027094
TI  - Neuroprotection by endogenous and exogenous PACAP following stroke.
AB  - We investigated the effects of PACAP treatment, and endogenous PACAP deficiency,
      on infarct volume, neurological function, and the cerebrocortical transcriptional
      response in a mouse model of stroke, middle cerebral artery occlusion (MCAO).
      PACAP-38 administered i.v. or i.c.v. 1 h after MCAO significantly reduced infarct
      volume, and ameliorated functional motor deficits measured 24 h later in wild
      type mice. Infarct volumes and neurological deficits (walking faults) were both
      greater in PACAP-deficient than in wild-type mice, but treatment with PACAP
      reduced lesion volume and neurological deficits in PACAP-deficient mice to the
      same level of improvement as in wild-type mice. A 35,546-clone mouse cDNA
      microarray was used to investigate cortical transcriptional changes associated
      with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP
      treatment after MCAO in wild-type mice. 229 known (named) transcripts were
      increased (228) or decreased (1) in abundance at least 50% following cerebral
      ischemia in wild-type mice. 49 transcripts were significantly up-regulated only
      at 1 h post-MCAO (acute response transcripts), 142 were up-regulated only at 24 h
      post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at
      both times (sustained response transcripts). More than half of these are
      transcripts not previously reported to be altered in ischemia. A larger
      percentage of genes up-regulated at 24 hr than at 1 hr required endogenous PACAP,
      suggesting a more prominent role for PACAP in later response to injury than in
      the initial response. This is consistent with a neuroprotective role for PACAP in
      late response to injury, i.e., even when administered 1 hr or more after MCAO.
      Putative injury effector transcripts regulated by PACAP include beta-actin,
      midline 2, and metallothionein 1. Potential neuroprotective transcripts include
      several demonstrated to be PACAP-regulated in other contexts. Prominent among
      these were transcripts encoding the PACAP-regulated gene Ier3, and the
      neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.

PMID- 17027095
TI  - Peroxisomes and aging.
AB  - Peroxisomes are indispensable for proper functioning of human cells. They
      efficiently compartmentalize enzymes responsible for a number of metabolic
      processes, including the absolutely essential beta-oxidation of specific fatty
      acid chains. These and other oxidative reactions produce hydrogen peroxide, which
      is, in most instances, immediately processed in situ to water and oxygen. The
      responsible peroxidase is the heme-containing tetrameric enzyme, catalase. What
      has emerged in recent years is that there are circumstances in which the tightly
      regulated balance of hydrogen peroxide producing and degrading activities in
      peroxisomes is upset-leading to the net production and accumulation of hydrogen
      peroxide and downstream reactive oxygen species. The factor most essentially
      involved is catalase, which is missorted in aging, missing or present at reduced
      levels in certain disease states, and inactivated in response to exposure to
      specific xenobiotics. The overall goal of this review is to summarize the
      molecular events associated with the development and advancement of peroxisomal
      hypocatalasemia and to describe its effects on cells. In addition, results of
      recent efforts to increase levels of peroxisomal catalase and restore oxidative
      balance in cells will be discussed.

PMID- 17027096
TI  - Primary hyperoxaluria type 1: AGT mistargeting highlights the fundamental
      differences between the peroxisomal and mitochondrial protein import pathways.
AB  - Primary hyperoxaluria type 1 (PH1) is an atypical peroxisomal disorder, as befits
      a deficiency of alanine:glyoxylate aminotransferase (AGT), which is itself an
      atypical peroxisomal enzyme. PH1 is characterized by excessive synthesis and
      excretion of the metabolic end-product oxalate and the progressive accumulation
      of insoluble calcium oxalate in the kidney and urinary tract. Disease in many
      patients is caused by a unique protein trafficking defect in which AGT is
      mistargeted from peroxisomes to mitochondria, where it is metabolically
      ineffectual, despite remaining catalytically active. Although the peroxisomal
      import of human AGT is dependent upon the PTS1 import receptor PEX5p, its PTS1 is
      exquisitely specific for mammalian AGT, suggesting the presence of additional
      peroxisomal targeting information elsewhere in the AGT molecule. This and many
      other functional peculiarities of AGT are probably a consequence of its rather
      chequered evolutionary history, during which much of its time has been spent
      being a mitochondrial, rather than a peroxisomal, enzyme. Analysis of the
      molecular basis of AGT mistargeting in PH1 has thrown into sharp relief some of
      the fundamental differences between the requirements of the peroxisomal and
      mitochondrial protein import pathways, particularly the properties of peroxisomal
      and mitochondrial matrix targeting sequences and the different conformational
      limitations placed upon importable cargos.

PMID- 17027097
TI  - The importomer--a peroxisomal membrane complex involved in protein translocation
      into the peroxisome matrix.
AB  - The import of proteins into the peroxisome matrix is an essential step in
      peroxisome biogenesis, which is critical for normal functioning of most
      eukaryotic cells. The translocation of proteins across the peroxisome membrane
      and the dynamic behavior of the import receptors during the import cycle is
      facilitated by several peroxisome-membrane-associated protein complexes, one of
      which is called the importomer complex [B. Agne, N.M. Meindl, K. Niederhoff, H.
      Einwachter, P. Rehling, A. Sickmann, H.E. Meyer, W. Girzalsky, W.H. Kunau, Pex8p:
      an intraperoxisomal organizer of the peroxisomal import machinery, Mol. Cell 11
      (2003) 635-646; P.P. Hazra, I. Suriapranata, W.B. Snyder, S. Subramani,
      Peroxisome remnants in pex3Delta cells and the requirement of Pex3p for
      interactions between the peroxisomal docking and translocation subcomplexes,
      Traffic 3 (2002) 560-574. ]. We provide below a brief historical perspective
      regarding the importomer and its role in peroxisome biogenesis. We also identify
      areas in which further work is needed to uncover the physiological role of the
      importomer.

PMID- 17027098
TI  - The ether lipid-deficient mouse: tracking down plasmalogen functions.
AB  - Chemical and physico-chemical properties as well as physiological functions of
      major mammalian ether-linked glycerolipids, including plasmalogens were reviewed.
      Their chemical structures were described and their effect on membrane fluidity
      and membrane fusion discussed. The recent generation of mouse models with ether
      lipid deficiency offered the possibility to study ether lipid and particularly
      plasmalogen functions in vivo. Ether lipid-deficient mice revealed severe
      phenotypic alterations, including arrest of spermatogenesis, development of
      cataract and defects in central nervous system myelination. In several cell
      culture systems lack of plasmalogens impaired intracellular cholesterol
      distribution affecting plasma membrane functions and structural changes of ER and
      Golgi cisternae. Based on these phenotypic anomalies that were accurately
      described conclusions were drawn on putative functions of plasmalogens. These
      functions were related to cell-cell or cell-extracellular matrix interactions,
      formation of lipid raft microdomains and intracellular cholesterol homeostasis.
      There are several human disorders, such as Zellweger syndrome, rhizomelic
      chondrodysplasia punctata, Alzheimer's disease, Down syndrome, and Niemann-Pick
      type C disease that are distinguished by altered tissue plasmalogen
      concentrations. The role plasmalogens might play in the pathology of these
      disorders is discussed.

PMID- 17027099
TI  - Prospective evaluation of atrial tachyarrhythmias in patients with interatrial
      block.
AB  - INTRODUCTION: Interatrial block (P-wave> or =110 ms) is clinically associated
      with left atrial enlargement and electromechanical dysfunction as well as atrial
      tachyarrhythmias. We prospectively evaluated the incidence of such arrhythmias,
      especially atrial fibrillation among patients with interatrial block over the
      course of 1 year. METHODS: 118 patients (aged 48 to 104 years; female 56.6%) who
      had been hospitalized between December 15, 2004 and January 14, 2005 were
      identified and divided into 3 groups based on their respective baseline
      electrocardiogram (interatrial block=41 patients, sinus non-interatrial block=51
      patients and atrial tachyarrhythmia=24 patients). Patients were subsequently
      followed for 12 months for pertinent cardiovascular events (heart failure,
      peripheral embolism, transient ischemic attacks and stroke), atrial
      tachyarrhythmias (atrial fibrillation and atrial flutter) and death as endpoints.
      RESULTS: 19 patients (17.9%) had atrial fibrillation during the 12-month follow
      up (sinus non-interatrial block group=4 [9.1%], interatrial block group=12
      [29.3%] and atrial tachyarrhythmia group=3 [14.3%]). Coronary artery disease,
      hypertension, pre-existing atrial fibrillation history, dilated cardiomyopathy,
      atrioventricular valvular disease and interatrial block (age- and sex-adjusted
      hazard ratio=4.2; 95% confidence interval 1.2-14.4; p=0.02) were significantly
      associated with future events of atrial fibrillation. However, logistic
      regression analysis indicated that interatrial block was not an independent
      predictor of future atrial fibrillation whereas only history of pre-existing
      atrial tachyarrhythmias was (hazard ratio=23.6; 95% confidence interval 4.5
      121.7; p=0.0002). CONCLUSION: Interatrial block may be associated with atrial
      fibrillation but in a 12-month period, does not appear to be an independent
      predictor of future atrial fibrillation. Continued prospective investigation of
      such a relationship is certainly warranted given its already known consequences.

PMID- 17027100
TI  - Sildenafil therapy for pulmonary arterial hypertension associated with atrial
      septal defects.
AB  - BACKGROUND: There is increasing evidence for beneficial effects of the type 5
      phosphodiesterase inhibitor, sildenafil, in idiopathic pulmonary arterial
      hypertension (PAH). The effects of sildenafil in severe PAH associated with an
      atrial septal defect (ASD) have not been clearly delineated. METHODS: This
      extended case series reviews our experience with sildenafil treatment in three
      patients with severe PAH and Eisenmenger syndrome associated with an ASD. Case
      notes were reviewed for baseline and follow-up anatomic, clinical and
      haemodynamic characteristics. RESULTS: Of three patients identified, median age
      44.3 years (range, 28 to 59 years), two had large secundum ASDs and the other a
      sinus venous defect. All patients had severe PAH and were desaturated at rest
      and/or during exercise. Sildenafil was started because of progressive and severe
      effort intolerance. All patients experienced symptomatic improvement, had higher
      arterial saturations (range 8-19%) and improvement in effort tolerance (88 m and
      56 m improvement in 6-min walk test distance (MWTD) in two patients). Right
      ventricular (RV) function and Doppler derived RV systolic pressure improved in
      two patients. Pulmonary arterial pressures decreased in two patients who had
      cardiac catheterization (range 4 to 14 mm Hg). Pulmonary vascular resistance
      decreased from 7.58 to 3.8 Wood's units in one patient who is now awaiting
      surgery. Another patient developed significant pulmonary vasoreactivity (8.3 to
      6.2 Wood's units with 100% oxygen) after 16 months of sildenafil therapy.
      CONCLUSIONS: Sildenafil not only relieves symptoms associated with severe PAH in
      patients with large ASDs, but also improves pulmonary arterial hemodynamics and
      RV function.

PMID- 17027101
TI  - Angina caused by coronary steal phenomenon.

PMID- 17027102
TI  - Atrial fibrillation is associated with increased neurohumoral activation and
      reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.
AB  - OBJECTIVES: To assess atrial fibrillation (AF) associated differences in
      proinflammatory cytokines, natriuretic peptide levels and exercise capacity in
      patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy
      (NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left
      ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III.
      Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6,
      tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal
      atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional
      class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients
      (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF
      duration compared to patients in sinus rhythm (SR). AF was associated with
      increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP
      (p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and
      slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to
      SR patients. No significant differences in cytokine and natriuretic peptide
      levels or exercise tolerance were noted when patients in AF were compared to the
      subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed
      that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently
      associated with the presence of AF in our patient population. CONCLUSION: AF is
      associated with increased inflammatory state, natriuretic peptide levels and
      reduced exercise capacity in patients with HF secondary to NIDC. These findings
      suggest that the presence of AF in HF represents a more advanced stage of the
      syndrome.

PMID- 17027103
TI  - The impact of cardiorespiratory fitness on inflammatory markers in patients with
      metabolic syndrome.

PMID- 17027104
TI  - Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic
      patients undergoing CABG.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) is known to negatively affect
      biological properties of venous vasculature, and, particularly, to reduce
      endothelium-derived nitric oxide release. This condition might influence venous
      graft function following coronary artery bypass surgery (CABG). The aim of this
      study was to evaluate the functional effects of a NO-releasing aspirin (NORA) on
      vein grafts (VG) of diabetics and control patients undergoing elective CABG.
      METHODS: In 40 consecutive ischemic heart disease patients, the effects of NORA
      were tested on segments of saphenous vein conduits harvested during elective
      CABG. Twenty patients had type-2 DM (mean age 69+/-2), whereas 20 patients had no
      DM (NDM) and represented the control group (mean age 67+/-4). Functional
      responses were tested by exposing VGs to NORA and to standard vasoactive agents
      in an organ-bath preparation. Histological features of VGs were also assessed by
      light and electronic microscopy. RESULTS: Significant impairment of endothelial
      dependent vasodilation (acetylcholine induced) was documented in VGs of DM
      subjects. NORA induced a significant and comparable vascular relaxation in all
      venous segments of NDM and DM patients (56+/-12% of maximal relaxation vs 61+/
      11% in the control group, respectively). Histology showed variable extent of
      vascular layer and cellular abnormalities in VGs of diabetics (intimal
      hyperplasia, calcific deposition, endothelial cell degeneration) likely
      responsible of the endothelial functional impairment, whereas control group VG
      showed preserved structures. CONCLUSIONS: This preliminary study confirms the
      impairment of endothelium-dependent vasodilative property of VGs in DM patients.
      It also indicates that NORA effectively induces vasodilation of VGs which was
      effective also in DM patients thereby representing a promising therapy for
      diabetics undergoing CABG with the use of VGs, although further studies are
      mandatory to conclusively assess the safety and benefits of this pharmacological
      agent.

PMID- 17027105
TI  - The last Swan song for the Swan-Ganz catheter?

PMID- 17027106
TI  - Plasma von Willebrand factor and soluble E-selectin levels in stable outpatients
      with systolic heart failure: the Frederiksberg heart failure study.
AB  - BACKGROUND: Endothelial dysfunction is a well-established aspect of the
      pathophysiology of patients with systolic heart failure. We have previously
      reported that patients who have had multiple current or previous hospital
      admissions for decompensated heart failure have consistently shown abnormal
      levels of plasma von Willebrand factor (vWf, an index of endothelial
      damage/dysfunction) and soluble E-selectin (E-sel, an index of endothelial
      activation), as well as other indices of endothelial perturbation. METHODS: To
      investigate if endothelial abnormalities extend to CHF outpatients who have only
      been recently diagnosed or have relatively mild or few, stable symptoms (at
      baseline), given the better prognosis in these patients, we performed a cross
      sectional analysis of CHF patients, where vWf and E-sel levels (as indices of
      endothelial perturbation) were measured (ELISA) and related to left ventricular
      ejection fraction (LVEF), exercise capacity (6-min walk test) and N-terminal pro
      Brain Natiuretic Peptide (NT-proBNP). RESULTS: There were no statistically
      significant differences in vWf and E-sel levels amongst patients with systolic
      heart failure compared to controls. Plasma NT-proBNP levels in patients with CHF
      were significantly elevated compared to controls (p<0.0001). Among the patients
      with CHF, higher NT-proBNP levels correlated with poorer LVEF [Spearman r=-0.244,
      p<0.004] and shorter 6-min walk distance [Spearman r=-0.226, p=0.045] but not
      NYHA class. Plasma vWf or E-sel levels did not correlate with LVEF, 6-min walk
      test or NYHA class. NT-proBNP levels correlated weakly with E-sel [Spearman r=
      0.211, p=0.015] but not vWf. CONCLUSION: The present observation suggests that
      stable CHF outpatients with few symptoms may in fact have less severe endothelial
      perturbation, as reflected by plasma indices such as vWf and E-selectin. There
      was limited association of endothelial indices to LVEF, exercise capacity, NYHA
      class and NT-proBNP levels.

PMID- 17027107
TI  - Obesity epidemic in modern China.

PMID- 17027108
TI  - Evaluation of 1MDS electropositive microfilters for simultaneous recovery of
      multiple microbe classes from tap water.
AB  - The 1MDS electropositive microfilter was designed specifically for virus capture
      and recovery from water, but its electrostatic properties raise the possibility
      that 1MDS filters can also effectively capture bacteria and parasites present in
      water samples. This filter is recommended by United States Environmental
      Protection Agency (USEPA) for recovering human enteric viruses from water
      matrices through the Virus Adsorption-Elution (VIRADEL) technique. If bacteria
      and parasites can also be concentrated and recovered using 1MDS filters, this
      sampling technique would have greater utility and cost-effectiveness for
      microbial water quality testing. In this study, both 142-mm flat and 25.4-cm
      cartridge 1MDS filters (Cuno) were tested to determine their effectiveness for
      recovery of MS2 and phi X174 bacteriophage, Salmonella enterica (serovar
      Typhimurium), Bacillus globigii endospores, and Cryptosporidium parvum oocysts
      from a tap water matrix. By amending the USEPA standard beef extract/glycine
      eluent with a surfactant (Tween 80) and dispersant (sodium polyphosphate) and
      varying the pH and temperature, multiple eluent conditions were compared in order
      to identify an optimum eluent for all organisms. While viruses, bacteria, and
      parasites are effectively retained by the 1MDS filter, elution efficiencies and
      associated recovery efficiencies varied for each organism.

PMID- 17027109
TI  - The effect of task preparation in task switching as reflected on lateralized
      readiness potential.
AB  - The present study examined whether task preparation had an equivalent beneficial
      effect for both switch and repeat trials in the context of a task switching
      paradigm. A pair-wise task-switching paradigm was used where each trial was
      comprised of two tasks that were either the same (task repeat) or different (task
      switch). The effect of preparation was manipulated so that participants either
      performed pure repeat trials or pure switch trials in separate blocks
      (foreknowledge conditions) or performed both switch and repeat trials within the
      same block (non-foreknowledge conditions). In addition, the time interval between
      the response to the first task and the onset of the next task's stimulus
      (response-stimulus interval, RSI) was set at either 300 ms or 600 ms. Both
      stimulus-locked and response-locked lateralized readiness potentials were
      measured to examine at what stage in time that task preparation affects the task
      performance. The results showed that task preparation had the same amount of
      beneficial effect on the stage of response selection for both switch and repeat
      trials, regardless of whether the RSI was short or long.

PMID- 17027111
TI  - Advances in graphonomics: studies on fine motor control, its development and
      disorders.
AB  - During the past 20 years graphonomic research has become a major contributor to
      the understanding of human movement science. Graphonomic research investigates
      the relationship between the planning and generation of fine motor tasks, in
      particular, handwriting and drawing. Scientists in this field are at the
      forefront of using new paradigms to investigate human movement. The 16 articles
      in this special issue of Human Movement Science show that the field of
      graphonomics makes an important contribution to the understanding of fine motor
      control, motor development, and movement disorders. Topics discussed include
      writer's cramp, multiple sclerosis, Parkinson's disease, schizophrenia, drug
      induced parkinsonism, dopamine depletion, dysgraphia, motor development,
      developmental coordination disorder, caffeine, alertness, arousal, sleep
      deprivation, visual feedback transformation and suppression, eye-hand
      coordination, pen grip, pen pressure, movement fluency, bimanual interference,
      dominant versus non-dominant hand, tracing, freehand drawing, spiral drawing,
      reading, typewriting, and automatic segmentation.

PMID- 17027110
TI  - Decomposing delta, theta, and alpha time-frequency ERP activity from a visual
      oddball task using PCA.
AB  - OBJECTIVE: Time-frequency (TF) analysis has become an important tool for
      assessing electrical and magnetic brain activity from event-related paradigms. In
      electrical potential data, theta and delta activities have been shown to underlie
      P300 activity, and alpha has been shown to be inhibited during P300 activity.
      Measures of delta, theta, and alpha activity are commonly taken from TF surfaces.
      However, methods for extracting relevant activity do not commonly go beyond
      taking means of windows on the surface, analogous to measuring activity within a
      defined P300 window in time-only signal representations. The current objective
      was to use a data driven method to derive relevant TF components from event
      related potential data from a large number of participants in an oddball
      paradigm. METHODS: A recently developed PCA approach was employed to extract TF
      components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005).
      Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314
      1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken
      from both individual trials and condition averages. Activity including
      frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to
      1312.5 ms were decomposed. RESULTS: A coordinated set of time-frequency events
      was apparent across the decompositions. Similar TF components representing
      earlier theta followed by delta were extracted from both individual trials and
      averaged data. Alpha activity, as predicted, was apparent only when time
      frequency surfaces were generated from trial level data, and was characterized by
      a reduction during the P300. CONCLUSIONS: Theta, delta, and alpha activities were
      extracted with predictable time-courses. Notably, this approach was effective at
      characterizing data from a single-electrode. Finally, decomposition of TF data
      generated from individual trials and condition averages produced similar results,
      but with predictable differences. Specifically, trial level data evidenced more
      and more varied theta measures, and accounted for less overall variance.

PMID- 17027112
TI  - A probiotic strain of Lactobacillus plantarum stimulates lymphocyte responses in
      immunologically intact and immunocompromised mice.
AB  - Experimental evidences showing the immunomodulatory effects of probiotic
      microorganisms have been provided by studies on immunologically intact animals.
      Here we compared the immunomodulation capacity of a probiotic strain of
      Lactobacillus plantarum on intact and cyclophosphamide-treated BALB/c mice.
      Although this strain fulfilled the in vitro criteria for the selection of
      potentially probiotic bacteria (resistance to low pH and bile, adhesion to
      epithelial cells and antimicrobial activity), it was unable to establish a
      persistent colonization in the gastrointestinal tract after intragastric gavage.
      The administration of L. plantarum did not modify the cyclophosphamide-induced
      leukopenia, but partially restored the proliferation of spleen cells from
      cyclophosphamide-treated mice in response to lipopolysaccharide. Our findings
      show that probiotic bacteria may exert immunomodulatory effects despite a limited
      colonization ability and may improve the immune function damaged by
      immunosuppressive agents.

PMID- 17027113
TI  - Expression of recombinant proteins lacking methionine as N-terminal amino acid in
      plastids: human serum albumin as a case study.
AB  - Removal of the N-terminal methionine of a protein could be critical for its
      function and stability. Post-translational modifications of recombinant proteins
      expressed in heterologous systems may change amino-terminal regions. We studied
      the expression of mature proteins lacking methionine as the N-terminal amino acid
      in tobacco chloroplasts, using human serum albumin (HSA) as an example. Two
      approaches were explored. First, we fused the Rubisco small subunit transit
      peptide to HSA. This chimeric protein was correctly processed in the stroma of
      the chloroplast and rendered the mature HSA. The second approach took advantage
      of the endogenous N-terminal methionine cleavage by methionine aminopeptidase.
      Study of this protein processing reveals a systematic cleavage rule depending on
      the size of the second amino acid. Analysis of several foreign proteins expressed
      in tobacco chloroplasts showed a cleavage pattern in accordance to that of
      endogenous proteins. This knowledge should be taken into account when recombinant
      proteins with N-terminus relevant for its function are expressed in plastids.

PMID- 17027114
TI  - The DE loop of the domain III of the envelope protein appears to be associated
      with West Nile virus neutralization.
AB  - The envelope (E) protein of WNV plays an important role in the virus
      neutralization. Using a mAb 5E8, a neutralizing epitope on the domain III of the
      E of the New York strain of WN virus was characterized. Results from
      neutralization-escape mutants and site-directed mutagenesis revealed that the 5E8
      epitope is a highly conformation dependent epitope consisting of at least
      residues E330, E332 and E367 on the domain III. Besides known critical
      neutralizing epitopes E330 and E332, our results indicate that residue E367, a
      component of DE loop on the domain III, appeared to be associated with
      neutralization but little with neuroinvasion of the virus, as reported previously
      (Beasley et al., 2002).

PMID- 17027115
TI  - [Camptocormia disclosing Parkinson's disease].
AB  - Camptocormia is characterised as an extreme bent-forward posture of the trunk
      that disappears in the recumbent position. On X-ray, trunk flexion appears
      without vertebral rotation as in scoliosis. The condition is a well-known
      complication of Parkinson's disease (PD) at the late stage. The authors present
      the case of a 77-year-old woman affected by severe camptocormia, which appeared
      and worsened in less than 6 months and hindered gait. Despite no signs of PD,
      neuro-imaging (DAT-Scan) showed an L-Dopa transducer decrease in putamens. A few
      weeks later, bradykinesia appeared and the clinical diagnosis of PD became more
      obvious. L-Dopa improved bradykinesia but did not change the bent-spine posture.
      A 1-year follow-up showed no other signs of PD other than bradykinesia, but the
      camptocormia was unchanged.

PMID- 17027116
TI  - Semi-automated CT segmentation using optic flow and Fourier interpolation
      techniques.
AB  - In radiotherapy treatment planning, tumor volumes and anatomical structures are
      manually contoured for dose calculation, which takes time for clinicians. This
      study examines the use of semi-automated segmentation of CT images. A few high
      curvature points are manually drawn on a CT slice. Then Fourier interpolation is
      used to complete the contour. Consequently, optical flow, a deformable image
      registration method, is used to map the original contour to other slices. This
      technique has been applied successfully to contour anatomical structures and
      tumors. The maximum difference between the mapped contours and manually drawn
      contours was 6 pixels, which is similar in magnitude to difference one would see
      in manually drawn contours by different clinicians. The technique fails when the
      region to contour is topologically different between two slices. A solution is
      recommended to manually delineate contours on a sparse subset of slices and then
      map in both directions to fill the remaining slices.

PMID- 17027117
TI  - Accumulation of p-hydroxybenzoic acid in hairy roots of Daucus carota.
AB  - We report here the accumulation of p-hydroxybenzoic acid in Agrobacterium
      rhizogenes-induced hairy root cultures of Daucus carota. This phenolic acid finds
      application in food, pharmaceutical and polymer industries. Metabolic profiling
      of phenolics by HPLC/ESI-MS from these hairy roots showed a considerable amount
      of p-hydroxybenzoic acid accumulation both in cytosol and in the cell wall.
      Analyses of HCl and NaOH treated soluble phenolic fractions resulted in the
      elution of peaks with same retention time and similar UV-absorption spectra as
      observed with p-hydroxybenzoic acid standard. This suggests that p-hydroxybenzoic
      acid is present in the cytosol as free-form (unconjugated). A correlation has
      been drawn between the accumulation of soluble and wall-bound phenolic acids on a
      time-course basis. An apparent absence of any p-hydroxybenzoic acid-glucoside
      supports this observation, which in turn encourages the idea of its incorporation
      in the cell wall in an alkaline-labile form.

PMID- 17027118
TI  - Transgenic rice plants ectopically expressing AtBAK1 are semi-dwarfed and
      hypersensitive to 24-epibrassinolide.
AB  - Brassinosteroids (BRs) are endogenous plant hormones essential for plant growth
      and development. Brassinosteroid insensitive1 (BRI1)-assocaiated receptor kinase
      (BAK1) is one of the key components in the BR signal transduction pathway due to
      its direct association with the BR receptor, BRI1. Although BRI1 and its
      orthologs have been identified from both dicotyledonous and monocotyledonous
      plants, less is known about BAK1 and its orthologs in higher plants other than
      Arabidopsis. This article provides the first piece of evidence that AtBAK1 can
      greatly affect growth and development of rice plants when ectopically expressed,
      suggesting that rice may share similar BR perception mechanism via BRI1/BAK1
      complex. Interestingly, transgenic rice plants displayed semi-dwarfism and
      shortened primary roots. Physiological analysis and cell morphology assay
      demonstrated that the observed phenotypes in transgenic plants were presumably
      caused by hypersensitivity to endogenous levels of BRs, different from BR
      insensitive and deficient rice mutants. Consistently, several known BR inducible
      genes were also upregulated in transgenic rice plants, further suggesting that
      BAK1 was able to affect BR signaling in rice. On the other hand, the transgenic
      plants generated by overproducing AtBAK1 may potentially have agricultural
      applications because the dwarfed phenotype is generally resistant to lodging,
      while the fertility remains unaffected.

PMID- 17027119
TI  - Effect of early decrease in the lesion size on late brain tissue loss,
      synaptophysin expression and functionality after a focal brain lesion in rats.
AB  - The purpose of the present study is to determine the effects of early decrease in
      the lesion size on late brain tissue loss, synaptogenesis and functionality after
      a focal brain lesion in rats. The lesion was induced either to the cortex using
      the photothrombotic ischemic stroke or to the striatum using the malonate
      poisoning model. The cortical and striatal lesions amounted to 66-80 mm(3) at day
      1 post-lesion and were reduced by 50% after the acute administration of dipyridyl
      (a liposoluble iron chelator) and aminoguanidine (an inhibitor of the inducible
      nitric oxide synthase), respectively. Loss of histologically intact tissue and
      synaptophysin expression as an indicator of synaptogenesis were examined at day
      35 post-lesion. Both types of lesion resulted in synaptophysin upregulation in
      contralateral and ipsilateral cortical areas. On the contrary, brain tissue loss
      was greater after the striatal (-17%) than the cortical lesion (-5%).
      Synaptophysin expression and tissue loss were not different between drug- and
      vehicle-treated rats. Moreover, a set of standard neurological tests revealed a
      difference in deficit between the both types of lesion, yet only in the acute
      post-lesion stage. However, it did not distinguish between vehicle- and drug
      treated rats whatever the lesion location. Our results indicate that late
      histological endpoints measurements are not recommended to probe the potential
      neuroprotective properties of a drug administered within the acute post-lesion
      stage. They also suggest that inhibition of cytotoxic mechanisms involved in
      lesion growth is of no clinical interest when it cannot lead to a long-term
      histological protection and/or increased synaptogenesis.

PMID- 17027122
TI  - Hepatitis B infection among health workers in Uganda: evidence of the need for
      health worker protection.
AB  - Hepatitis B exposure was assessed in 311 health workers in Uganda, a highly
      endemic country. Health workers were selected by random sampling from a
      categorized list of health workers at district level, proportionate to the
      population of each district. Whereas 60.1% of health workers have evidence of
      hepatitis B infection, with 8.7% being chronic carriers and one (0.3%) acutely
      infected, 36.3% are still susceptible and could benefit from vaccination. Only
      5.1% reported having had at least one dose of hepatitis B vaccine and 3.5% were
      apparently immune through vaccination. Needle stick injuries reported by 77% of
      health workers were the most common mode of exposure to blood and body fluids.
      Trends suggested duration of service as a predictor while age and history of
      blood transfusion remained significant independent risk factors for hepatitis B
      infection. 98% of health workers are willing to be vaccinated. These results
      confirm the need for protection and vaccination of health workers in Uganda
      against hepatitis B.

PMID- 17027123
TI  - Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae
      infection.
AB  - Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia
      which leads to high economic losses in the swine industry worldwide. Vaccination
      against this pathogen is hampered by the occurrence of 15 serotypes, and commonly
      used whole cell bacterin vaccines are not sufficiently cross-serotype protective.
      In addition, for generating and maintaining specified pathogen-free herds it is
      desirable to use DIVA (differentiating infected from vaccinated animals)
      vaccines. Based on a detergent wash extraction of outer membrane associated
      proteins and secreted proteins we developed a DIVA vaccine using the immunogenic
      ApxII toxin which is present in 13 of the 15 A. pleuropneumoniae serotypes as the
      DIVA antigen. The apxIIA gene was deleted in one strain each of serotypes 1, 2,
      and 5 using a single-step transconjugation system, and equal parts of detergent
      washes from these strains served as the vaccine antigen. After intramuscular
      immunisation all pigs developed a strong humoral immune response to the vaccine
      antigen and showed no reactivity in an ApxIIA ELISA. Upon challenge all pigs were
      completely protected from clinical symptoms in trials with a homologous (serotype
      2) as well as with a heterologous strain (serotype 9); in addition, colonisation
      of the challenge strain was clearly reduced but not abolished completely. As a
      result of the highly efficient protection, however, immunised pigs did not
      develop antibodies to the DIVA-antigen at levels detectable by ELISA but only by
      a more sensitive Western blotting approach, thereby demonstrating the challenge
      in developing appropriate marker vaccines for the livestock industry.

PMID- 17027124
TI  - Protective immune responses to a multi-gene DNA vaccine against Staphylococcus
      aureus.
AB  - To investigate the strategy of using a multivalent polyprotein DNA vaccine
      against Staphylococcus aureus, a series of plasmids was used to immunize mice
      followed by infectious challenge. The plasmid vaccines expressed Clumping factor
      A (Clfa), fibronectin binding protein A (FnBPA) and the enzyme Sortase (Srt) as
      single proteins or combined as a polyprotein. All animals produced a mixed Th1
      and Th2 response including functional antigen-specific, mostly IgG2a antibodies,
      sustained production of IFN-gamma and a predominantly CD8+ T-cell response. Upon
      challenge with a virulent S. aureus isolate (Sa042), after 21 days, 55% of the
      multi-gene vaccinated mice survived infection compared to only 15% of the control
      groups. Vaccinated mice showed no signs of arthritis when challenged with the
      less virulent "Newman" strain that caused reactive arthritis in the controls. The
      results suggest that a multi-gene polyprotein-expressing nucleic acid vaccine
      alone produces a combined Th1 and Th2 response that can contribute to protection
      against the complex pathogenesis of S. aureus.

PMID- 17027126
TI  - A cost-effectiveness analysis of radon protection methods in domestic properties:
      a comparative case study in Brixworth, Northamptonshire, UK.
AB  - Building regulations in the UK have since 1992 required that radon-proof
      membranes be installed in new domestic properties to protect residents against
      the adverse effects of radon. This study compares the cost-effectiveness of the
      current regulatory regime with an alternative that would entail new properties
      being tested for radon after construction, and being remediated if necessary. The
      alternative regime is found to be more cost-effective for a sample of properties
      in Brixworth, Northamptonshire, UK. For this regime, the central estimate of cost
      per quality-adjusted life-year gained, the measure of cost-effectiveness used, is
      2869 pounds compared to 6182 pounds for installing membranes, results suggesting
      a case for re-examining the current regulations on radon protection in new
      properties. Pilot studies will, however, be needed to consider how different
      means of protecting residents of new properties against radon might operate in
      practice and to provide improved evidence on their relative cost-effectiveness.

PMID- 17027125
TI  - Comparative proteomics analysis to annexin B1 DNA and protein vaccination in
      mice.
AB  - DNA vaccines have been widely reported to elicit both effective humoral and
      cellular immune responses, but the mechanisms of antigen processing and
      presentation in DNA immunization is still ambiguous. Aiming to molecular
      mechanisms involved in DNA immunization, comparative serum proteomics was
      introduced to discover differentially expressed proteins after different
      immunizations. Using two-dimensional electrophoresis and matrix-assisted laser
      desorption ionisation-time-of-flight mass spectrometry, 23 three-fold or greater
      up-regulated proteins were separated and identified, including 14 from ANXB1 DNA
      immunized mice and 9 from annexin B1 protein immunized mice. The
      histocompatibility class I molecule H2-Q10 (HA10_MOUSE) and proteasome activator
      PA28 alpha-subunit (PSME1_MOUSE) were found up-regulated in ANXB1 DNA immunized
      mice, which may contribute to the augmented activation of T lymphocytes. These
      proteins may serve as potential surrogate markers of successful vaccination and
      provide research targets for molecular mechanisms of vaccinology.

PMID- 17027127
TI  - Changes in the inferior alveolar nerve following sagittal split ramus osteotomy
      in monkeys: a comparison of monocortical and bicortical fixation.
AB  - We aimed to observe the changes in the inferior alveolar nerve (IAN) after
      bilateral sagittal split ramus osteotomy (SSRO) using monocortical or bicortical
      screw fixation. Bilateral SSRO for setback of the mandible was done in 12
      monkeys, and monocortical or bicortical fixation was applied on opposing sides of
      each mandible. Sensory nerve action potentials were tested before and immediately
      after operation, and at 2, 4, 8, and 12 weeks. Six animals selected randomly were
      killed at 4 and 12 weeks after the operation. Specimens of nerve were harvested
      and processed for histological examination and electron microscopic analysis.
      Obvious prolongation of latency and diminution of amplitude in the IAN were found
      postoperatively. At 4 weeks after operation, Wallerian degeneration was apparent,
      and there were signs of axonal regeneration in the nerves. The IAN had more
      abnormalities of evoked potentials and pathological changes after bicortical than
      after monocortical fixation. Although considerable recovery was found after both
      forms of fixation at 12 weeks, the function of the nerve after plate fixation was
      better than after screw fixation. Our results suggest that the nerve damage
      during SSRO could be temporary and reversible, and monocortical fixation may
      result in restoration of the nerve function sooner than bicortical fixation.

PMID- 17027128
TI  - Endodontic reoperation using an endoscope and microsurgical instruments: One year
      follow-up.
AB  - Endodontic reoperation was required for 30 teeth with periapical lesions in 18
      patients, using microsurgical instruments and a 6cm long and 3mm wide endoscope
      for magnification. Reoperation was successful in 14 patients after 1 year.

PMID- 17027129
TI  - Penetrating injury of the facial skeleton through the orbit, by a massive
      metallic shotgun block: A case report.
AB  - We present a case of invasion of the orbit and the infra-temporal fossa by a
      massive breechblock from a shotgun. The block was removed and two months later
      the orbit was reconstructed with iliac crest. Six months after that the patient
      had plastic surgery and insertion of ocular prosthesis.

PMID- 17027130
TI  - Meniscal screw fixation provides sufficient stability to prevent tears from
      gapping.
AB  - BACKGROUND: Many meniscal fixation implants have low pull-out forces. It is still
      unknown if these forces are higher than the forces the implants must resist in
      vivo. It was hypothesized that meniscal repair with the meniscal screw as an
      example for a device of low pull-out force significantly reduces tear gapping.
      METHODS: Longitudinal tears were set in the posterior horn of the medial menisci
      of porcine knee joints. To observe the tears a translucent placeholder copying
      the original articular surface replaced the medial tibial plateau. The knees were
      moved in a loading and motion simulator under various external moments and axial
      loads and gapping of the tear was registered. The measurements were repeated
      after fixation of the tears with three ClearFix Screws, which show a low pull-out
      force of 20N only. FINDINGS: Maximum gapping (median 1.6mm, min/max 1.1/1.8mm)
      occurred at 200N axial joint load under the combination of a valgus and external
      rotation moment. Fixation with the ClearFix Screw significantly reduced tear
      gapping in all load cases. INTERPRETATION: Moderate joint loads only lead to
      small gaps of meniscal tears. Meniscal fixation with the ClearFix Screw prevents
      longitudinal meniscal tears from gapping. This could indicate from a
      biomechanical point of view that fixation implants of low pull-out strength are
      not in danger of failure in a normal rehabilitation regimen.

PMID- 17027131
TI  - Compositional assessment of event DAS-59122-7 maize using substantial
      equivalence.
AB  - Event DAS-59122-7 (Herculex RW) maize (Zea mays L.) plants were transformed to
      express the Cry34Ab1 and Cry35Ab1 binary insecticidal crystal proteins originally
      isolated from Bacillus thuringiensis Berliner (Bt) strain PS149B1. These proteins
      protect maize roots from attack by corn rootworms, Diabrotica spp. DAS-59122-7
      maize also contains the pat gene, originally isolated from Streptomyces
      viridochromogenes, which confers tolerance to glufosinate-ammonium herbicides
      (e.g. Liberty). We assessed the composition of these transgenic plants (with and
      without Liberty herbicide treatment), grown at a total of eight fields sites over
      2 years, by applying the principle of substantial equivalence. Forage and grain
      samples were analyzed for proximates, fiber and minerals, and grain was further
      analyzed for amino acids, fatty acids, vitamins, secondary metabolites and anti
      nutrients. Data plots were prepared that allow for efficient investigation of
      equivalency between event DAS-59122-7 maize and a non-transgenic near-isogenic
      maize line grown contemporaneously. Results demonstrated that DAS-59122-7 maize
      is equivalent to non-transgenic maize with respect to these important
      constituents.

PMID- 17027132
TI  - Effects of bilateral eye movements on gist based false recognition in the DRM
      paradigm.
AB  - The effects of saccadic bilateral (horizontal) eye movements on gist based false
      recognition was investigated. Following exposure to lists of words related to a
      critical but non-studied word participants were asked to engage in 30s of
      bilateral vs. vertical vs. no eye movements. Subsequent testing of recognition
      memory revealed that those who undertook bilateral eye movement were more likely
      to correctly recognise previously presented words and less likely to falsely
      recognise critical non-studied associates. This result joins other research in
      demonstrating the conditions in which false memory effects can be attenuated.

PMID- 17027133
TI  - Posture recognition in Alzheimer's disease.
AB  - BACKGROUND: Apraxia is neurologically induced deficit in the ability perform
      purposeful skilled movements. One of the most common forms is ideomotor apraxia
      (IMA) where spatial and temporal production errors are most prevalent. IMA can be
      associated Alzheimer's disease (AD), even early in its course, but is often not
      identified possibly because the evaluation of IMA by inexperienced judges using
      performance tests is unreliable. The purpose of this study, therefore, is to
      learn if the Postural Knowledge Test (PKT), a praxis discrimination test that
      assesses knowledge of transitive (PKT-T subtest) and intransitive (PKT-I subtest)
      postures and does not require extensive training, is as sensitive and specific as
      the praxis performance tests. METHODS: We studied 15 subjects with probable AD as
      well as 18 age-matched controls by having them perform transitive and
      intransitive gestures to command and imitation, as well as having them
      discriminate between correct and incorrect transitive and intransitive postures.
      RESULTS: Overall on all tests, the control subjects performed better than those
      with AD. In addition all subjects had more trouble with transitive than
      intransitive gestures. Using a stepwise discriminative analysis, 81.8% of the
      subjects could be classified according to Group (94.4% of Controls, 66.7% of AD
      subjects). In this analysis, the PKT-T (transitive posture subtest) was the only
      measure that contributed to the discrimination of subjects. CONCLUSION: We found
      that having subjects select the correct transitive hand postures in this "booklet
      test" was more sensitive than grading their praxis performances even when using
      judges with extensive training. This suggests that this discrimination test might
      be an excellent means for diagnosing and screening patients for AD. The reason
      why recognition of transitive postures is relatively more difficult for our AD
      subjects is not known. Two possibilities are that the representations for
      intransitive movements are stronger than those for transitive movements, and
      hence, more resistant to degradation, or that intransitive acts are stored in
      parts of the brain not affected by AD.

PMID- 17027134
TI  - Activation of premotor vocal areas during musical discrimination.
AB  - Two same/different discrimination tasks were performed by amateur-musician
      subjects in this functional magnetic resonance imaging study: Melody
      Discrimination and Harmony Discrimination. Both tasks led to activations not only
      in classic working memory areas--such as the cingulate gyrus and dorsolateral
      prefrontal cortex--but in a series of premotor areas involved in vocal-motor
      planning and production, namely the somatotopic mouth region of the primary and
      lateral premotor cortices, Broca's area, the supplementary motor area, and the
      anterior insula. A perceptual control task involving passive listening alone to
      monophonic melodies led to activations exclusively in temporal-lobe auditory
      areas. These results show that, compared to passive listening tasks,
      discrimination tasks elicit activation in vocal-motor planning areas.

PMID- 17027136
TI  - Assessing 12(S)-lipoxygenase inhibitory activity using colorectal cancer cells
      overexpressing the enzyme.
AB  - 12(S)-Lipoxygenase (LOX) is regarded as a pro-tumorigenic enzyme and as a
      potential target for therapy and prevention of cancer so that the search for
      specific 12(S)-LOX inhibitors is part of drug development strategies. To
      facilitate the identification of specific 12(S)-LOX inhibitors we have created an
      assay cell line by introducing a12(S)-LOX expression vector into SW480 colorectal
      cancer cells. When arachidonic acid was supplied in the medium both transiently
      and stably overexpressing cells produced 12(S)-hydroxytetraenic acid (HETE)
      originating from the transfected gene at 4-5-fold the amount obtained from
      control transfectants. 12(S)-HETE production was 1913.7+/-17.2pg/ml and reached a
      steady state level 24h after addition of arachidonic acid. To demonstrate the
      models suitability of 12(S)-LOX overexpressing SW480 cells they were used to
      measure the inhibitory activity of the plant phenols baicalein, kaempferol,
      quercetin, nordihydroguaretic acid and resveratrol which are known for their
      chemopreventive as well as LOX-inhibitory activity in different tumour models.
      All 5 compounds inhibited 12(S)-HETE production at concentrations below those
      necessary for growth inhibition.

PMID- 17027137
TI  - Lack of immunogenicity of ice structuring protein type III HPLC12 preparation
      administered by the oral route to human volunteers.
AB  - Before a novel protein can be used in foods, its potential allergenicity must be
      assessed. In this study, healthy volunteers consumed ice structuring protein
      (ISP) Type III preparation or a control material 5 days a week for a total of 8
      weeks. General measures of health were recorded during the study, and the
      immunogenicity of the protein was assessed by monitoring the levels of IgG and
      IgE antibodies specific for ISP Type III. The participants remained in good
      health throughout the study and during the 4 week follow-up period. No IgG or IgE
      antibodies specific for ISP Type III were detected in the blood of the
      participants. Investigations of immunogenicity in man have not been previously
      applied in the context of safety evaluation and they do not form part of the
      regimens proposed for the evaluation of protein allergenicity. Consequently no
      standardised protocols exist for such studies, nor any background against which
      to interpret the results. Nevertheless, the absence of an immune response using a
      protocol which could have been expected to result in a response with a strongly
      immunogenic protein, confirms the conclusions of earlier published work, and
      attests to the lack of allergenicity of ISP Type III preparation.

PMID- 17027138
TI  - Effects of fluoroquinolones on HERG channels and on pancreatic beta-cell ATP
      sensitive K+ channels.
AB  - An inhibition of the cardiac rapid delayed rectifier K(+) current (I(Kr)) and of
      the ATP-sensitive K(+) (K(ATP)) current seems to be involved in the mechanisms of
      the cardiotoxic effects and the alterations in glucose homeostasis, respectively,
      induced by some fluoroquinolones. The aim of the present study was to compare the
      effects of fluoroquinolone derivatives on the pore-forming subunit of the cardiac
      I(Kr), which is encoded by human ether-a-go-go-related gene (HERG), and on the
      ATP-sensitive K(+) (K(ATP)) channel from the clonal insulinoma cell line RINm5F.
      Sparfloxacin blocked HERG currents half-maximally (IC(50) value) at a
      concentration of 33.2 microM, whereas norfloxacin and lomefloxacin each tested at
      a concentration of 300 microM inhibited HERG currents only by 2.8+/-3.6% and
      12.3+/-4.7%, respectively. Four newly synthesized fluoroquinolone derivatives
      with either a p-fluoro-phenyl (compound C3) or an o-fluoro-phenyl (compound C4)
      substituent at position N(1) and an additional dimethylated piperazine ring
      (compounds C1 and C2) inhibited HERG currents by 7.3-14.7% at test concentrations
      of 100 microM. The rank order of potency for the inhibition of K(ATP) currents
      was C2>C1, C4, sparfloxacin>C3. In conclusion, the structural requirements for
      fluoroquinolones to inhibit I(Kr) currents and K(ATP) currents appear to differ.
      The amino group at position C(5) seems to be primarily responsible for the strong
      HERG current blocking property of sparfloxacin. In contrast, for the block of
      pancreatic beta-cell K(ATP) currents by fluoroquinolones the substituents at
      positions N(1), C(7) and C(8) all might play a role.

PMID- 17027139
TI  - Clinical wear of posterior metal-free polymer crowns. One-year results from a
      randomized clinical trial.
AB  - OBJECTIVES: The purpose of this randomized clinical trial was to evaluate the
      clinical wear behavior of posterior, metal-free polymer crowns, with and without
      a glass-fiber framework, and to compare it with that of metal-ceramic crowns.
      METHODS: Eighty single crowns manufactured from a newly designed polymer
      composite were set in posterior teeth. Half of these received a glass-fiber
      framework (group 1) whereas half were prepared without framework stabilization
      (group 2). All polymer crowns were adhesively luted with resin cement. As the
      control group, 40 conventional metal-ceramic crowns were inserted with hybrid
      cement. Wear was measured, by use of gypsum replicas, at baseline and after 12
      months, by use of a 3D laser scanner. Statistical analysis was performed using
      mixed-effects regression model analyses. RESULTS: The mean total wear of
      posterior single crowns was -8.1 microm (+/-9.7 microm) in group 1, -7.0 microm
      (+/-9.1 microm) in group 2, and -3.4 microm (+/-6.3 microm) in the control group.
      Statistical analysis revealed wear behavior was significantly different from the
      control group for group 1 (p=0.014) and group 2 (p<0.01). No significant
      difference was detected between groups 1 and 2. Age, gender, and opposing teeth
      had no significant effect on wear behavior. CONCLUSIONS: Within a 12-month
      observation period mean total wear of posterior polymer crowns with and without a
      glass-fiber framework was significantly greater than for metal-ceramic crowns.
      The selection of restorative materials should be based on knowledge of clinical
      wear in order to preserve occlusal stability.

PMID- 17027140
TI  - A dose-response curve for the negative bias pressure of an intrathoracic pressure
      regulator during CPR.
AB  - An intrathoracic pressure regulator (ITPR) is a device that can be added to the
      external end of a tracheal tube to create controlled negative airway pressure
      between positive pressure ventilations. The resulting downward bias of the airway
      pressure baseline promotes increased venous return and enhanced circulation
      during CPR and also during hypovolemic shock. In the present study, we exercised
      a mathematical model of the human cardiopulmonary system, including airways,
      lungs, a four chambered heart, great vessels, peripheral vascular beds, and the
      biomechanics of chest compression and recoil, to determine the relationship
      between systemic perfusion pressure during CPR and the value of baseline negative
      airway pressure in an ITPR. Perfusion pressure increases approximately 50% as
      baseline airway pressure falls from zero to -10 cm H2O. Thereafter perfusion
      pressure plateaus. Negative bias pressures exceeding -10 cm H2O are not needed in
      ITPR-CPR.

PMID- 17027141
TI  - Short-schedule intravesical gemcitabine with ablative intent in recurrent Ta-T1,
      G1-G2, low- or intermediate-risk, transitional cell carcinoma of the bladder.
AB  - OBJECTIVES:  PRIMARY OBJECTIVE: to assess ablative efficacy and tolerability of
      short-schedule intravesical gemcitabine for intact, low- and intermediate-risk,
      recurrent superficial bladder tumours. SECONDARY OBJECTIVE: to assess effect on
      prophylaxis. METHODS: Patients with a diagnosis of recurrence and a history of
      previous superficial, low- or intermediate-risk bladder tumours were selected for
      the study. They received 2000 mg gemcitabine in 50 ml, that is 40 mg/ml,
      intravesically, weekly for 4 wk, followed by resection of any residual lesions.
      Complete responses consisted of absence of any macroscopic, histologically
      confirmed, residual lesion, and no response in the presence of residual lesions.
      The effect on prophylaxis was measured in months as disease-free interval to
      first recurrence, and as percentage of patients recurring within the first 12 mo.
      Toxicity was assessed as local and systemic. RESULTS: Of 34 recruited patients,
      28 consecutive patients were evaluable, with complete responses observed in 13 of
      28 (46.4%) and no response in 15 (53.6%). Median time to first recurrence was 9.1
      mo (range: 2.9-26.5) for 19 of 28 (67.8%) patients experiencing recurrence during
      the first year. Local or systemic toxicity was observed in 9 of 34 (26.4%)
      patients, resulting in protocol interruption in 6 patients. CONCLUSIONS:
      Intravesical gemcitabine alone showed ablative efficacy in nearly one half of the
      patients under study. Drug tolerability was good, both locally and systemically.

PMID- 17027142
TI  - PhotoMEA: an opto-electronic biosensor for monitoring in vitro neuronal network
      activity.
AB  - PhotoMEA is a biosensor useful for the analysis of an in vitro neuronal network,
      fully based on optical methods. Its function is based on the stimulation of
      neurons with caged glutamate and the recording of neuronal activity by Voltage
      Sensitive fluorescent Dyes (VSD). The main advantage is that it will be possible
      to stimulate even at sub-single neuron level and to record with high resolution
      the activity of the entire network in the culture. A large-scale view of neuronal
      intercommunications offers a unique opportunity for testing the ability of drugs
      to affect neuronal properties as well as alterations in the behaviour of the
      entire network. The concept and a prototype for validation is described here in
      detail.

PMID- 17027143
TI  - A bio-inspired visual collision detection mechanism for cars: combining insect
      inspired neurons to create a robust system.
AB  - The lobula giant movement detector (LGMD) of locusts is a visual interneuron that
      responds with an increasing spike frequency to an object approaching on a direct
      collision course. Recent studies involving the use of LGMD models to detect car
      collisions showed that it could detect collisions, but the neuron produced
      collision alerts to non-colliding, translating, stimuli in many cases. This study
      presents a modified model to address these problems. It shows how the neurons pre
      synaptic to the LGMD show a remarkable ability to filter images, and only
      colliding and translating stimuli produce excitation in the neuron. It then
      integrates the LGMD network with models based on the elementary movement detector
      (EMD) neurons from the fly visual system, which are used to analyse directional
      excitation patterns in the biologically filtered images. Combining the
      information from the LGMD neuron and four directionally sensitive neurons
      produces a robust collision detection system for a wide range of automotive test
      situations.

PMID- 17027145
TI  - Positive feedback of hepatic angiotensinogen expression in silver sea bream
      (Sparus sarba).
AB  - The renin-angiotensin system (RAS) is involved in the maintenance of fluid
      homeostasis in vertebrates. Production of the precursor protein, angiotensinogen,
      is regulated by other components within the RAS. Angiotensin II (Ang II)
      stimulates the production and secretion of angiotensinogen in many mammalian
      models. However, the existence of a similar positive feedback mechanism for
      angiotensinogen has not been demonstrated for any non-mammalian species. In the
      present study, we have cloned the angiotensinogen for silver sea bream (Sparus
      sarba) and investigated the role of Ang II on angiotensinogen expression. The
      nucleotide sequence of angiotensinogen for S. sarba only exhibits a fair
      resemblance to other fish angiotensinogens and shows 76.6% similarity to that of
      Takifugu rubripes and 57.2% similarity to that of Danio rerio. Angiotensinogen
      transcripts have been identified in the brain, liver, kidney, and various parts
      of the intestine of sea bream, an observation, which probably implies the
      presence of a local RAS at the tissue level. The liver is probably the major
      source of angiotensinogen, as it exhibits the highest angiotensinogen transcript
      abundance among different tissues. Differential angiotensinogen expression was
      found among different regions of the intestine where the pyloric caeca exhibits
      the highest expression. Putative Ang I is identified at the N-terminal of the
      deduced protein with a novel sequence [Asn1, Ile5, His9]-Ang I. Hepatic
      angiotensinogen expression in sea bream adapted to different salinities remained
      constant and this is probably due to desensitization of the angiotensin receptors
      by angiotensin. A positive feedback mechanism of angiotensinogen by Ang II has
      been demonstrated as exogenous Ang II increased the amount of angiotensinogen
      transcript in isolated hepatocytes in vitro. Blockade of endogenous RAS by the
      angiotensin converting enzyme (ACE) inhibitor, captopril, significantly lowered
      the hepatic expression of angiotensinogen in vivo. The effect of Ang II
      stimulation on angiotensinogen expression is more potent in fish than that in
      mammals. These data suggest that the positive feedback mechanism of
      angiotensinogen by Ang II has already evolved in teleosts and such mechanism may
      be involved in the maintenance of angiotensinogen secretion under resting and
      hypertensive conditions.

PMID- 17027146
TI  - Efects of growth hormone and cadmium on the transcription regulation of two
      metallothionein isoforms.
AB  - The effect of growth hormone (GH) and cadmium (Cd) on metallothionein (MT)
      expression was investigated in hepatoma cells. In fish the constitutive isoform
      MT-B and the metal-responsive MT-A are expressed. Real-time RT-PCR revealed that:
      Cd up-regulates mostly MT-A, GH slightly induces MT-B and the GH/Cd combination
      induces synergistically both MTs. Perturbations in Ca2+ levels suppressed or
      reduced the Cd-induction of MTs and abolished the GH/Cd synergy. Similar results
      were obtained by inhibition of tyrosine kinases. Also the signaling molecules
      recruited by the GH receptor responded differently to GH and Cd, with ERKs
      showing a synergistic activation upon GH/Cd. The following conclusions can be
      drawn: (1) cytosolic Ca2+ is mainly involved in MT-A regulation; (2) both Ca2+
      and tyrosine phosphorylation are essential for Cd-induction and GH/Cd synergy on
      MTs. The synergy could depend on interactions in different signaling pathways,
      leading to a differential recruitment of MTF-1 and AP-1 transcription factors.

PMID- 17027144
TI  - Differential regulation of CREB and ERK phosphorylation through corticotropin
      releasing factor receptors type 1 and 2 in AtT-20 and A7r5 cells.
AB  - The corticotropin-releasing factor (CRF) family of peptides generally exerts its
      biological actions by binding to two major subtypes of CRF receptors: CRF
      receptor type 1 (CRF1 receptor) and CRF receptor type 2 (CRF2 receptor). In this
      study, we investigated the mechanism by which three ligands altered
      phosphorylation of CREB and ERK 1/2, using AtT-20 cells (expressing CRF1
      receptor) and A7r5 cells (expressing CRF2 receptor). Incubation with 100 nM of
      CRF, urocortin 1 (UCN 1), or UCN 2 increased CREB phosphorylation. The protein
      kinase A pathway was involved in the CRF- or UCN-mediated increase in CREB
      phosphorylation in both cell lines. Bisindolylmaleimide partially inhibited the
      CRF-mediated increase in CREB phosphorylation, but only in AtT-20 cells,
      suggesting that the protein kinase C pathway is involved in regulation of CREB
      phosphorylation via CRF1 receptor but not CRF2 receptor. CRF increased ERK
      phosphorylation in AtT-20 cells, whereas the UCNs decreased it in A7r5 cells.
      Bisindolylmaleimide partially inhibited the UCN-mediated decrease in ERK
      phosphorylation in A7r5 cells, suggesting that the protein kinase C pathway is
      partially involved in CRF2 receptor signal transduction. In AtT-20 cells, the
      mitogen-activated protein kinase kinase pathway regulated ERK phosphorylation
      following CRF1 receptor activation. These findings suggest differential
      regulation of CREB and ERK 1/2 phosphorylation through CRF receptors.

PMID- 17027147
TI  - Alternative splicing in angiogenesis: the vascular endothelial growth factor
      paradigm.
AB  - Alternative splicing, first discovered in the 1970s, has emerged as one of the
      key generators of proteomic diversity. Not surprisingly, alternative splicing is
      increasingly linked to the etiology of cancer. This is illustrated by vascular
      endothelial growth factor (VEGF), the dominant angiogenic factor. Recently, an
      antiangiogenic family of VEGF isoforms was discovered, and termed VEGF(xxx)b.
      VEGF(xxx)b isoforms arise from an alternative 3' splice site in exon 8, and
      differ by a mere six amino acids at the C-terminus. These alternative six amino
      acids radically change the functional properties of VEGF. VEGF(xxx)b isoform
      expression is regulated in human tissues and development, and disregulated in
      many pathological states including cancer. Understanding what regulates
      VEGF(xxx)b alternative splicing, and therefore the balance of pro- and
      antiangiogenic isoforms is of great importance and will be explored in detail
      over the next few years.

PMID- 17027148
TI  - The retinoid X receptor-selective ligand, LGD1069, inhibits tumor-induced
      angiogenesis via suppression of VEGF in human non-small cell lung cancer.
AB  - The present study determined the influence of a retinoid X receptor agonist
      LGD1069 on angiogenesis in non-small cell lung cancer. In A549 xenograft models,
      treatment with LGD1069 inhibited the growth and CD31 expression compared with
      control. In vivo angiogenesis assay utilizing hollow fiber, LGD1069 reduced
      density of capillary network induced by tumor cells. To determine the basis of
      these observations, we examined the expression of VEGF and activation of JNK and
      ERK in A549 cells exposed to LGD1069. Our data showed that LGD1069 decrease the
      VEGF expression of tumor cells in a dose-dependent manner. Furthermore, it was
      demonstrated that the decreasing expression of VEGF was consist with inhibition
      of JNK and ERK activation induced by LGD1069. Collectively, our results suggest a
      role of LGD1069 in treatment for non-small cell lung cancer by inhibition of
      tumor-induced angiogenesis.

PMID- 17027149
TI  - Neural drive preservation after detraining following neuromuscular electrical
      stimulation training.
AB  - The purpose of the study was to investigate the behaviour of the central nervous
      system when 5 weeks of neuromuscular electrical stimulation (NMES) training was
      followed by 5 weeks of detraining. Nineteen males were divided into the
      neuromuscular electrostimulated group (EG, n=12) and the control group (CG, n=7).
      The training program consisted of 15 sessions of isometric NMES over a 5-week
      period. The EG subjects were tested before training (PRE), after 5 weeks of NMES
      training (POST) and after 5 weeks of detraining (DE) while CG subjects were only
      tested at PRE and at POST. Soleus (SOL) and gastrocnemii (GAS) maximal H-reflex
      and M-wave potentials were evoked at rest (i.e., H(max) and M(max), respectively)
      and during maximal voluntary contraction (MVC) (i.e., H(sup) and M(sup),
      respectively). SOL and GAS V-wave were recorded by supramaximal stimulation
      delivered during MVC. SOL and GAS electromyographic (EMG) activity as well as
      muscle activation were also assessed during MVC. After training, plantar flexor
      MVC increased significantly by 22% (P<0.001). Torque gains were associated with
      an increase in muscle activation (P<0.05), SOL and GAS normalized EMG activity
      (P<0.01 and P<0.05, respectively) and V/M(sup) ratios (P<0.01 and P<0.05,
      respectively). No significant changes occurred in any of these parameters between
      POST and DE. H(max)/M(max) and H(sup)/M(sup) ratios for both muscles were
      unchanged after both the training and detraining periods. In conclusion, the NMES
      training-induced neural adaptations were maintained after detraining, suggesting
      that neural changes are long-lasting and did not affect the elements of H-reflex
      pathways.

PMID- 17027150
TI  - Distribution of choline acetyltransferase immunoreactivity in the alimentary
      tract of the barnacle Balanus amphitrite (Cirripedia, Crustacea).
AB  - To date only peptidergic innervation has been described in the alimentary tract
      of barnacles. In the present work the presence and distribution of choline
      acetyltransferase (ChAT), the acetylcholine (ACh) synthesizing enzyme, was
      investigated by immunohistochemistry in the alimentary tract of the adult
      barnacle Balanus amphitrite. Numerous ChAT-immunoreactive (IR) cells and a net of
      ChAT-IR cytoplasmic processes were localized inside the epithelium of the
      posterior midgut, close to the basement membrane; no IR nerve endings were
      detected in the midgut longitudinal and circular muscle bundles. Epithelial
      neurons or endocrine cells in the gut epithelium have been described in some
      invertebrate species belonging to different taxa and their peptidergic features
      are reported in the literature. Our results point out the presence of
      neuroepithelial cells also in the gut epithelium of barnacles; moreover, for the
      first time, a cholinergic feature is suggested for this cell type. These data
      seem to indicate the involvement of ACh in the gut functions of barnacle and
      suggest that the barnacle alimentary tract is more complex than previously
      thought and requires further study.

PMID- 17027151
TI  - Potential participation of cystatin C in rapid eye movement sleep (REMS)
      modulation.
AB  - It has been hypothesized that proteins modulate rapid eye movement sleep (REMS).
      Studies have shown an increase in the liberation of proteins in the mesencephalic
      reticular formation of cats during REMS. It has also been determined that protein
      synthesis inhibitors diminish REMS and that protease-inhibitors increase this
      sleep phase. These and other studies support the importance of "di novo" protein
      molecules in sleep, and in particular, in REMS regulation. In this context, it is
      important to determine the role of endogenous proteases and their endogenous
      inhibitors in sleep regulation. In this study, we found that Cystatin C (CC), an
      endogenous protease inhibitor, diminishes wakefulness and increases REMS. We have
      also found an increase in CC expression after REMS deprivation and a tendency to
      decrease after a 2 h period of REMS rebound. We further showed that REMS
      deprivation increases the expression of Cathepsin H (CH), a protease inhibited by
      CC. These results suggest that naturally occurring protease-inhibitors enhance
      REMS, perhaps by facilitating the availability of proteins.

PMID- 17027152
TI  - Association analysis of NAD(P)H:quinone oxidoreductase gene 609 C/T polymorphism
      with Alzheimer's disease.
AB  - Alterations of the NAD(P)H:quinone oxidoreductase (NQO1) activity are associated
      with Alzheimer's disease (AD). A polymorphism consisting of a single nucleotide
      (C-->T) change at position 609 of NQO1 influences the NQO1 activity. Therefore
      the NQO1 C609T polymorphism may confer susceptibility for AD developing. To test
      the hypothesis, we have performed an association study between the NQO1 gene
      polymorphism C609T and late-onset Alzheimer's disease (LOAD) in Chinese
      population. Totally 104 LOAD patients and 128 controls were enrolled in our data
      set. All subjects were genotyped for NQO1 and Apolipoprotein E (APOE). There were
      no significant differences in NQO1 genotype or allele frequencies between cases
      and controls. Likewise, with the stratification of APOE psilon4 status, no
      statistical difference was observed between cases and controls. Our findings
      suggested that this polymorphism might not represent additional genetic risk
      factor for LOAD. However, the present study cannot exclude NQO1 as a possible
      candidate for LOAD. Further study in a larger population and biological
      functional analysis of NQO1 gene is required to verify the role of NQO1 in LOAD.

PMID- 17027153
TI  - Response delay and spatial representation in pointing movements.
AB  - Pointing movements decrease in accuracy when target information is removed before
      movement onset. This time effect was analyzed in relation with the spatial
      representation of the target location, which can be egocentric (i.e. in relation
      to the body) or exocentric (i.e. in relation to the external world) depending on
      the visual environment of the target. The accuracy of pointing movements
      performed without visual feedback was measured in two delay conditions: 0 and 5-s
      delay between target removal and movement onset. In each delay condition, targets
      were presented either in the darkness (egocentric localization) or within a
      structured visual background (exocentric localization). The results show that
      pointing was more accurate when targets were presented within a visual background
      than in the darkness. The time-related decrease in accuracy was observed in the
      darkness condition, whereas no delay effect was found in the presence of a visual
      background. Therefore, contextual factors applied to a simple pointing action
      might induce different spatial representations: a short-lived sensorimotor
      egocentric representation used in immediate action control, or a long-lived
      perceptual exocentric representation which drives perception and delayed action.

PMID- 17027154
TI  - Use of the Faces Pain Scale by left and right hemispheric stroke patients.
AB  - No pain scale is available for stroke patients due to the presence of language or
      cognitive disorders. However, the Faces Pain Scale (FPS), which was initially
      developed for children, has been used with success in adults with cognitive
      impairments. The aim of this study is to test whether the FPS could be used in
      left or right hemispheric stroke patients (LHSP, RHSP). One hundred twenty-seven
      stoke patients and 21 controls were recruited in 2 rehabilitation units.
      Construct validity of FPS was assessed by rating and ranking facial expressions.
      FPS was correlated to a Visual Analog Scale (VAS) and to a Verbal Rating Scale
      (VRS) for the assessment of shoulder pain. Reliability was determined by test
      retest procedures. Performances of RHSP in the ranking and rating procedures were
      very poor compared to LHSP and to controls. However, in the assessment of
      patients' shoulder pain, FPS scores were highly correlated with VAS and VRS in
      both stroke groups (r=0.65-0.82, p<10(-3)). FPS was more reliable in LHSP than in
      RHSP. It was preferred to VAS and VRS in LHSP, while in RHSP VAS was the
      preferred scale. The present study provides preliminary support for the validity
      and the reliability of FPS in LHSP. However, we do not recommend its sole use in
      stroke patients. Further studies are needed to determine whether FPS can be used
      in stroke patients for assessing changes in severity of pain over time.

PMID- 17027155
TI  - Stereotyped topography of different elevated contingent negative variation
      components in children with migraine without aura points towards a subcortical
      dysfunction.
AB  - Increased negativity during contingent negative variation (CNV) is thought to
      reflect abnormal neural activation in adult migraineurs' attention related
      processing. Findings in childhood and adolescence have yielded less clear
      results. This study characterizes the age-dependent development of CNV topography
      in migraine during childhood in order to elucidate the origin and cerebral
      generators of described CNV elevations. A large sample of children with primary
      headache (migraine with/without aura, tension type headache) and healthy controls
      aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution
      DC-EEG. Patients were tested for diagnose-related topographic group differences
      of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation
      (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed
      elevated negativity over the supplementary motor area (SMA) and around the
      vertex. Migraine children lacked age-dependent development of late CNV around Cz
      as previously reported. However, they showed a normal development of late CNV
      over pre-/primary motor cortex (MI). There was no marked elevation of iCNV
      amplitude over frontal areas (orienting reaction) nor specific amplitude
      elevations over "motor" or "sensory" areas during sustained attention (late CNV).
      Additional "pre-mature" activation e.g., in the locus coeruleus (leading to
      diffuse cortical activation summing up to a maximum over the vertex) or the basal
      ganglia (interacting with SMA) explained the rather stereotyped CNV elevation
      around the vertex better than a specific implication of the cortical systems
      responsible for orienting, motor preparation or sensory attention.

PMID- 17027156
TI  - Two rare clinical manifestations of coenurosis in sheep.
AB  - Two rare clinical manifestations of coenurosis in sheep are reported. (i) A case
      of partial seizure disorder in a ram of 11 months old. During seizure episodes
      the animal lay down in lateral recumbency displaying initially a stuporous
      condition and subsequently began to revolve its head from the base of the cervix.
      At the necropsy of the case, Coenurus cerebralis cyst (young bladder worm) was
      found dorsally inside the brainstem, in the site of the tectum mesencephaly. (ii)
      The second-reported manifestation was a bacterial meningoengephalitis that was
      witnessed in two lambs of 6-7 weeks old. The lambs displayed lateral recumbency
      with seizure activity. At necropsy, meningoencephalitis with congestion and
      abscesses were observed in both of them. Interestingly, C. cerebralis cysts were
      also found in both brains. Streptococcus dysgalactiae was isolated from the
      abscesses. Possibly, S. dysgalactiae translocation of the blood-brain barrier was
      facilitated by the migration of the immature stages of C. cerebralis to and
      through the brain.

PMID- 17027157
TI  - Anticoccidial effect of green tea-based diets against Eimeria maxima.
AB  - Anticoccidial effects of green tea (GT)-based diets were evaluated in chickens
      following oral infection with Eimeria maxima an ubiquitous intestinal parasite of
      poultry that impairs the growth and feed efficiency of infected birds. Five-week
      old chickens were assigned to four groups (GT 0.5%, GT 2.0%, untreated/infected
      and non-infected control) and each group consisted of 15 chickens. Chickens were
      fed a standard diet supplemented with ground green tea for 2 weeks prior to
      infection with E. maxima (10,000 sporulated oocysts per bird). The effects of
      green tea on E. maxima infection were assessed by two parameters, fecal oocyst
      shedding and body weight gain. The green tea-fed chickens produced significantly
      reduced fecal oocysts (P<0.05) when compared to the E. maxima-infected group fed
      standard diet. The green tea-based diet, however, did not improve body weight
      loss caused by E. maxima infection. This study is the first to demonstrate
      anticoccidial effect of green tea on Eimeria parasites.

PMID- 17027158
TI  - Therapeutic and persistent efficacy of spinosad applied as a pour-on or a topical
      spray against natural infestations of chewing and sucking lice on cattle.
AB  - Studies were conducted in Wisconsin and Illinois, USA, to assess and compare the
      therapeutic and persistent efficacy of spinosad when applied as either a pour-on
      or topical spray and compared with cyfluthrin pour-on and coumaphos topical spray
      for controlling natural infestations of chewing (Bovicola bovis) and sucking
      (Linognathus vituli, Solenopotes capillatus and Haematopinus eurysternus) lice on
      cattle. Thirty-five animals at each trial site were blocked according to pre
      treatment lice counts and randomly allocated to one of five treatment groups:
      single treatments of spinosad (25 g/L), diluted with water to 0.04% active
      ingredient and applied as a whole-body topical spray; spinosad (25 g/L) applied
      as a neat pour-on at 2 mg/kg body weight; Co-Ral Emulsifiable Livestock
      Insecticide (5.8% coumaphos), diluted to 0.03% active ingredient and applied as a
      whole-body topical spray; CyLence Pour-on Insecticide (1% cyfluthrin), applied as
      a neat pour-on at the manufacturer's recommended use rate for lice; and untreated
      control. Both spinosad treatments and cyfluthrin provided > or =96% control of B.
      bovis for up to 7 weeks, whereas the efficacy of coumaphos dropped to <90% after
      week 5 at one site. Spinosad spray had the best therapeutic and residual control
      of all treatments against L. vituli, > or =98% for at least 5 weeks at both
      sites, compared with 3 weeks for coumaphos at one site. Spinosad and coumaphos
      sprays provided 100% control of S. capillatus for at least 8 weeks compared with
      > or =97% control for spinosad and cyfluthrin pour-on treatments over the same
      interval. While H. eurysternus burden was low and limited to one study site, all
      four treatments provided 100% control for at least 6 weeks. These studies showed
      that topically applied spinosad provided a high degree of therapeutic and
      residual control against both sucking and chewing lice.

PMID- 17027159
TI  - Cellular senescence and cancer treatment.
AB  - Cellular senescence, an irreversible cell-cycle arrest, reflects a safeguard
      program that limits the proliferative capacity of the cell exposed to endogenous
      or exogenous stress signals. A number of recent studies have clarified that an
      acutely inducible form of cellular senescence may act in response to oncogenic
      activation as a natural barrier to interrupt tumorigenesis at a premalignant
      level. Paralleling the increasing insights into premature senescence as a tumor
      suppressor mechanism, a growing line of evidence identifies cellular senescence
      as a critical effector program in response to DNA damaging chemotherapeutic
      agents. This review discusses molecular pathways to stress-induced senescence,
      the interference of a terminal arrest condition with clinical outcome, and the
      critical overlap between premature senescence and apoptosis as both tumor
      suppressive and drug-responsive cellular programs.

PMID- 17027160
TI  - Methemoglobinemia by cerium nitrate poisoning.
AB  - Cerium nitrate is a topical antiseptic used with silver sulfadiazine
      (Flammacerium) for the treatment of serious burns. This topical agent can induce
      methemoglobinemia, but no cases have been reported in the recent literature. In
      this article, we present the case of a 16-year old girl, with third-degree burns
      over 95% of her body. After daily dressings of Flammacerium, on the sixth day she
      developed a bluish skin coloring. When tested for methemoglobinemia, levels of
      31.8% were found. These returned to normal after classic treatment with Methylene
      blue.

PMID- 17027161
TI  - Treatment of flexion contractures following burns in extremities.
AB  - In order to release and cover defects in burn contractures over joints, several
      surgical procedures have been proposed. Skin grafting is easy to do, but it
      requires immobilization, and tends to contract again, different types of flaps
      without skin grafting are alternatives. These flaps have their specific
      indications, limitations and some disadvantages such as a bulky, unattractive
      appearance in donor or recipient sites, partial necrosis, and sometimes patients
      dissatisfaction. Considering these points, the authors proposed a new technique
      composed of a Y-V advancement in the middle and two scar releases proximal and
      distal to the joint which were covered with full thickness skin grafts. This
      seems to have some advantages in both case of technique and more patients
      satisfaction. In the current study, the authors presented their results with
      different methods of treatment, which they performed for burn flexion
      contractures in limbs. Ninety-one operations were performed in 74 patients, the
      method of reconstruction included skin grafting in 43 contractures, local flaps
      in 16, pediculated flaps in 11, and the new combined approach in 21 cases. Width
      of scar was one of the main factors for selection of choice option. This proposed
      technique is especially appropriate for scars which cover 10-60% of joint surface
      area. Advantages of this combined technique are coverage of joint area with a
      pretty normal skin flap, and enough scar lengthening due to combination of Y-V
      advancement and skin grafted released areas.

PMID- 17027162
TI  - Neuropeptide Y regulates recurrent mossy fiber synaptic transmission less
      effectively in mice than in rats: Correlation with Y2 receptor plasticity.
AB  - A unique feature of temporal lobe epilepsy is the formation of recurrent
      excitatory connections among granule cells of the dentate gyrus as a result of
      mossy fiber sprouting. This novel circuit contributes to a reduced threshold for
      granule cell synchronization. In the rat, activity of the recurrent mossy fiber
      pathway is restrained by the neoexpression and spontaneous release of
      neuropeptide Y (NPY). NPY inhibits glutamate release tonically through activation
      of presynaptic Y2 receptors. In the present study, the effects of endogenous and
      applied NPY were investigated in C57Bl/6 mice that had experienced pilocarpine
      induced status epilepticus and subsequently developed a robust recurrent mossy
      fiber pathway. Whole cell patch clamp recordings made from dentate granule cells
      in hippocampal slices demonstrated that, as in rats, applied NPY inhibits
      recurrent mossy fiber synaptic transmission, the Y2 receptor antagonist (S)-N2
      [[1-[2-[4-[(R,S)-5,11-dihydro-6(6H)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2
      oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H
      1,2,4-triazol-4-yl]ethyl]-argininamide (BIIE0246) blocks its action and BIIE0246
      enhances synaptic transmission when applied by itself. Y5 receptor agonists had
      no significant effect. Thus spontaneous release of NPY tonically inhibits
      synaptic transmission in mice and its effects are mediated by Y2 receptor
      activation. However, both NPY and BIIE0246 were much less effective in mice than
      in rats, despite apparently equivalent expression of NPY in the recurrent mossy
      fibers. Immunohistochemistry indicated greater expression of Y2 receptors in the
      mossy fiber pathway of normal mice than of normal rats. Pilocarpine-induced
      status epilepticus markedly reduced the immunoreactivity of mouse mossy fibers,
      but increased the immunoreactivity of rat mossy fibers. Mossy fiber growth into
      the inner portion of the dentate molecular layer was associated with increased Y2
      receptor immunoreactivity in rat, but not in mouse. These contrasting receptor
      changes can explain the quantitatively different effects of endogenously released
      and applied NPY on recurrent mossy fiber transmission in mice and rats.

PMID- 17027164
TI  - Glutamate reduces secretion of l-serine in astrocytes isolated from stroke-prone
      spontaneously hypertensive rats.
AB  - In the CNS, l-serine (l-Ser) plays an essential role in neuronal survival by
      evoking a variety of biological responses in glial cells. Initially, we examined
      whether glutamate, hydrogen peroxide (H(2)O(2)), interleukin-1 (IL-1) beta, and
      sodium nitroprusside (SNP) induce the secretion of l-Ser in astrocytes isolated
      from Wistar Kyoto rats (WKY). The secretion of l-Ser was significantly induced
      with glutamate and SNP in cultured astrocytes. Next, to gain insight into the
      involvement of l-Ser in glutamate-induced neuroprotection, we compared the
      secretion of l-Ser in astrocytes isolated from stroke-prone spontaneously
      hypertensive rats (SHRSP) and normotensive rats, WKY. We also examined the mRNA
      expression of the enzyme that produces l-Ser, 3-phosphoglycerate dehydrogenase
      (PHGDH), and a neural amino acid transporter, ASCT1, in the cultured astrocytes.
      A dose-dependent study of glutamate in astrocytes of SHRSP indicated differences
      in the secretion of l-Ser, and gene expression of PHGDH and ASCT1, compared with
      levels in the WKY astrocytes. We demonstrated that both the secretion and the
      gene expression were significantly attenuated in glutamate-treated astrocytes
      from SHRSP. Cerebral ischemia in SHRSP induced a massive efflux of glutamate,
      causing delayed neuronal death in region CA1 of the hippocampus. The results
      suggest that the attenuated secretion of l-Ser in astrocytes is involved in
      neuronal vulnerability and survival in SHRSP during the production of glutamate,
      as the secretion of l-Ser, which is stimulated by glutamate, is closely related
      to the protective effect against glutamate-mediated neurotoxicity. We conclude
      that glutamate and SNP up-regulate the secretion of l-Ser in primary astrocytes.
      Secretion of l-Ser is regulated in astrocytes in response to glutamate and nitric
      oxide and may correspond to the level of l-Ser needed for neuronal survival
      during brain insults such as ischemic stroke in SHRSP.

PMID- 17027163
TI  - Fos responses of dopamine neurons to sociosexual stimuli in male zebra finches.
AB  - Dopamine (DA) is produced in numerous brain areas and influences a wide variety
      of social behaviors, but very few data are available to establish the socially
      relevant response properties of most DA populations, which comprise eight cell
      groups numbered A8-A15. Anatomically, these DA populations are evolutionarily
      conserved, and all have been identified in both birds and mammals. We now report
      the Fos responses of tyrosine hydroxylase-immunoreactive (TH-ir; putatively
      dopaminergic) neurons in the A8-A15 cell groups of male zebra finches following
      exposure to a control condition or one of six different social stimuli: a
      heterospecific male, conspecific male, fighting in a mate competition paradigm
      (which includes both male and female stimuli), a courtship interaction without
      physical contact, a courtship interaction with physical contact but no mounting,
      and a courtship interaction with mounting. We found that the DA cell groups
      exhibit distinctive profiles of responsiveness to social stimuli. Fos induction
      in A8, A9, A10 and midbrain A11 neurons increased significantly in response to a
      variety of conspecific stimuli, but not heterospecific stimuli. In contrast, Fos
      induction in the preoptic A14 neurons was observed specifically in response to
      sexual interactions, and Fos induction in hypothalamic A11 neurons appears to
      primarily reflect the performance of courtship singing. Infundibular A12 neurons,
      which may be involved in stress-related processes, showed the highest level of
      TH+Fos colocalization in control subjects. This colocalization decreased in
      response to all conspecific stimuli except fighting, and did not decrease
      following exposure to a heterospecific male.

PMID- 17027165
TI  - Muscle inflammation induces a rapid increase in calcitonin gene-related peptide
      (CGRP) mRNA that temporally relates to CGRP immunoreactivity and nociceptive
      behavior.
AB  - Recent data support an important role for calcitonin gene-related peptide (CGRP)
      in deep tissue nociceptive processing. Using real-time reverse transcriptase
      polymerase chain reaction (RT-PCR), radioimmunoassay, immunohistochemistry and
      behavioral testing, we studied the early time course of CGRP mRNA and protein
      expression as well as nociceptive behavior following muscle inflammation. A rapid
      and significant increase in CGRP mRNA occurred in the mandibular division (V3) of
      the ipsilateral trigeminal ganglion at 30 minutes, 4 and 24 h after the injection
      of complete Freund's adjuvant as an inflammatory agent into rat masseter muscle.
      No change in mRNA occurred in the ipsilateral ophthalmic and maxillary divisions
      (V1/V2) or in the contralateral V3. The levels of immunoreactive calcitonin gene
      related peptide (iCGRP) in the ipsilateral V3 significantly increased at 1, 4 and
      24 h following muscle inflammation. In contrast, no change occurred in iCGRP
      levels in either the ipsilateral V1/V2 or contralateral V3. When saline was
      injected into the masseter muscle, the levels of mRNA or iCGRP did not change in
      the ipsilateral V3 suggesting that the biochemical changes are specific to CFA
      induced muscle inflammation. The number of muscle afferent neurons immunoreactive
      for CGRP was significantly reduced compared with control at 1, 4 and 24 h in the
      ipsilateral but not in the contralateral trigeminal ganglion following
      inflammation. This decrease in the ipsilateral ganglion may indicate a loss of
      intrasomatic CGRP as a result of increased axonal transport away from the
      neuronal cell body and/or release of CGRP. Behavioral testing showed a reduction
      in head withdrawal thresholds bilaterally from 30 min through 24 h following
      muscle inflammation. Thus upregulation of CGRP mRNA and iCGRP levels are
      temporally related to the development of inflammation and lowered pain
      thresholds. The present data support the hypothesis that CGRP is upregulated
      during deep tissue inflammation and suggest that gene transcription is involved
      in this upregulation.

PMID- 17027166
TI  - Subcellular localization of nicotinamide adenine dinucleotide phosphate oxidase
      subunits in neurons and astroglia of the rat medial nucleus tractus solitarius:
      relationship with tyrosine hydroxylase immunoreactive neurons.
AB  - Superoxide produced by the enzyme nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase mediates crucial intracellular signaling cascades in the medial
      nucleus of the solitary tract (mNTS), a brain region populated by
      catecholaminergic neurons, as well as astroglia that play an important role in
      autonomic function. The mechanisms mediating NADPH oxidase (phagocyte oxidase)
      activity in the neural regulation of cardiovascular processes are incompletely
      understood, however the subcellular localization of superoxide produced by the
      enzyme is likely to be an important regulatory factor. We used immunogold
      electron microscopy to determine the phenotypic and subcellular localization of
      the NADPH oxidase subunits p47(phox), gp91(phox,) and p22(phox) in the mNTS in
      rats. The mNTS contains a large population of neurons that synthesize
      catecholamines. Significantly, catecholaminergic signaling can be modulated by
      redox reactions. Therefore, the relationship of NADPH oxidase subunit labeled
      neurons or glia with respect to catecholaminergic neurons was also determined by
      dual labeling for the superoxide producing enzyme and tyrosine hydroxylase (TH),
      the rate-limiting enzyme in catecholamine biosynthesis. In the mNTS, NADPH
      oxidase subunits were present primarily in somatodendritic processes and
      astrocytes, some of which also contained TH, or were contacted by TH-labeled
      axons, respectively. Immunogold quantification of NADPH oxidase subunit
      localization showed that p47(phox) and gp91(phox) were present on the surface
      membrane, as well as vesicular organelles characteristic of calcium storing
      smooth endoplasmic reticula in dendritic and astroglial processes. These results
      indicate that NADPH oxidase assembly and consequent superoxide formation are
      likely to occur near the plasmalemma, as well as on vesicular organelles
      associated with intracellular calcium storage within mNTS neurons and glia. Thus,
      NADPH oxidase-derived superoxide may participate in intracellular signaling
      pathways linked to calcium regulation in diverse mNTS cell types. Moreover, NADPH
      oxidase-derived superoxide in neurons and glia may directly or indirectly
      modulate catecholaminergic neuron activity in the mNTS.

PMID- 17027167
TI  - The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is
      unaffected by restraint stress or adrenalectomy.
AB  - The vasopressin 1b receptor (Avpr1b) is one of two principal receptors mediating
      the behavioral effects of vasopressin (Avp) in the brain. Avpr1b has recently
      been shown to strongly influence social forms of aggression in mice and hamsters.
      This receptor appears to play a role in social recognition and motivation as well
      as in regulating the hypothalamic-pituitary-adrenal axis. Most of these studies
      have been performed in knockout mice, a species in which the localization of the
      Avpr1b has not been described, thus precluding correlations with the behaviors.
      We performed in situ hybridization histochemistry (ISHH) with specific probes and
      found especially prominent expression within the CA2 pyramidal neurons of the
      hippocampus, with much lower expression in the hypothalamic paraventricular
      nucleus and amygdala. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      confirmed expression in those as well other areas in which the ISHH was not
      sensitive enough to detect labeled cells (e.g. piriform cortex, septum, caudate
      putamen and lower brainstem areas). Mouse Avpr1b transcript levels were not
      altered in the CA2 field by restraint stress or adrenalectomy. Finally, ISHH and
      RT-PCR showed expression of the Avpr1b gene in the rat and human hippocampi as
      well. We suggest that the CA2 field may form or retrieve associations (memories)
      between olfactory cues and social encounters.

PMID- 17027168
TI  - Contribution of epoxyeicosatrienoic acids to the hypoxia-induced activation of
      Ca2+ -activated K+ channel current in cultured rat hippocampal astrocytes.
AB  - Brief hypoxia differentially regulates the activities of Ca(2+)-activated K(+)
      channels (K(Ca)) in a variety of cell types. We investigated the effects of
      hypoxia (<2% O(2)) on K(Ca) channel currents and on the activities of cytochrome
      P450 2C11 epoxygenase (CYP epoxygenase) in cultured rat hippocampal astrocytes.
      Exposure of astrocytes to hypoxia enhanced macroscopic outward K(Ca) current,
      increased the open state probability (NPo) of 71 pS and 161 pS single-channel
      K(Ca) currents in cell-attached patches, but failed to increase the NPo of both
      the 71 pS and 161 pS K(Ca) channel currents recorded from excised inside-out
      patches. The hypoxia-induced enhancement of macroscopic K(Ca) current was
      attenuated by pretreatment with tetraethylammonium (TEA, 1 mM) or during
      recording using low-Ca(2+) external bath solution. Exposure of astrocytes to
      hypoxia was associated with generation of superoxide as detected by staining of
      cells with the intracellular superoxide detection probe hydroethidine (HE),
      attenuation of the hypoxia-induced activation of unitary K(Ca) channel currents
      by superoxide dismutation with tempol, and as quantitated by high-pressure liquid
      chromatography/fluorescence assay using HE as a probe. In cultured astrocytes in
      which endogenous CYP epoxygenase activity has been inhibited with either
      miconazole or N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MSPPOH)
      hypoxia failed to increase the NPo of both the 71 pS and 161 pS K(Ca) currents
      and generation of superoxide. Hypoxia increased the level of P450 epoxygenase
      protein and production of epoxyeicosatrienoic acids (EETs) from cultured
      astrocytes, as determined by immunohistochemical staining and LC/MS analysis,
      respectively. Exogenous 11,12-EET increased the NPo of both the 71 pS and 161 pS
      K(Ca) single-channel currents only in cell-attached but not in excised inside-out
      patches of cultured astrocytes. These findings indicate that hypoxia enhances the
      activities of two types of unitary K(Ca) currents in astrocytes by a mechanism
      that appears to involve CYP epoxygenase-dependent generation of superoxide and
      increased production or release of EETs.

PMID- 17027169
TI  - Galanin inhibits neural activity in the subfornical organ in rat slice
      preparation.
AB  - The activation of the subfornical organ (SFO), a circumventricular organ, induces
      water intake and vasopressin release. Since central administrations of galanin
      (GAL) suppress water intake and vasopressin release, GAL may inhibit the neural
      activity of SFO neurons. In the present study, we investigated effects of GAL on
      the SFO using molecular biological, electrophysiological and anatomical
      techniques. Reverse transcription-polymerase chain reaction analysis demonstrated
      the presence in the SFO of rats of the mRNAs for each of the three known GAL
      receptor subtypes (GalR1, GalR2 and GalR3). In extracellular recordings in SFO
      slice preparations, GAL dose-dependently inhibited the neural activity of cells
      from a number of recording sites. Many GAL-sensitive SFO neurons showed
      excitatory responses to angiotensin II (ANGII). The GalR1 agonist M617 inhibited
      the activity of SFO neurons, whereas the GalR2 and GalR3 agonist GAL(2-11) had
      almost no effect. In patch-clamp recordings, GAL induced an outward current in
      SFO neurons without influencing synaptic currents. An immunoelectron microscopic
      study revealed the existence of GAL-containing synaptic vesicles in the SFO.
      These results suggest that the SFO has neural inputs involving GAL. The response
      to GAL is inhibitory, mediated at least in part by GalR1 and provides a plausible
      explanation for the opposite effects of ANGII and GAL seen in vivo on water
      intake and vasopressin release.

PMID- 17027170
TI  - Metallothionein-I and -III expression in animal models of Alzheimer disease.
AB  - Previous studies have described altered expression of metallothioneins (MTs) in
      neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and
      Alzheimer's disease (AD). In order to gain insight into the possible role of MTs
      in neurodegenerative processes and especially in human diseases, the use of
      animal models is a valuable tool. Several transgenic mouse models of AD amyloid
      deposits are currently available. These models express human beta-amyloid
      precursor protein (AbetaPP) carrying different mutations that subsequently result
      in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have
      evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in
      three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring
      the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F
      mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA
      levels were induced in all transgenic lines studied, although the pattern of
      induction differed between the models. In the Tg2576 mice MT-I was weakly
      upregulated in cells surrounding Congo Red-positive plaques in the cortex and
      hippocampus. A more potent induction of MT-I was observed in the cortex and
      hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques
      content. MT-I upregulation was also more significant in Tg-SwDI mice, especially
      in the subiculum and hippocampus CA1 area. Immunofluorescence stainings
      demonstrate that astrocytes and microglia/macrophages surrounding the plaques
      express MT-I&II. In general, MT-I regulation follows a similar but less potent
      response than glial fibrillary acidic protein (GFAP) expression. In contrast to
      MT-I, MT-III mRNA expression was not significantly altered in any of the models
      examined suggesting that the various MT isoforms may have different roles in
      these experimental systems, and perhaps also in human AD.

PMID- 17027171
TI  - A vital role for voltage-dependent potassium channels in dopamine transporter
      mediated 6-hydroxydopamine neurotoxicity.
AB  - 6-Hydroxydopamine (6-OHDA), a neurotoxic substrate of the dopamine transporter
      (DAT), is widely used in Parkinson's disease models. However, the molecular
      mechanisms underlying 6-OHDA's selectivity for dopamine neurons and the injurious
      sequelae that it triggers are not well understood. We tested whether ectopic
      expression of DAT induces sensitivity to 6-OHDA in non-dopaminergic rat cortical
      neurons and evaluated the contribution of voltage-dependent potassium channel
      (Kv)-dependent apoptosis to the toxicity of this compound in rat cortical and
      midbrain dopamine neurons. Cortical neurons expressing DAT accumulated dopamine
      and were highly vulnerable to 6-OHDA. Pharmacological inhibition of DAT
      completely blocked this toxicity. We also observed a p38-dependent Kv current
      surge in DAT-expressing cortical neurons exposed to 6-OHDA, and p38 antagonists
      and Kv channel blockers were neuroprotective in this model. Thus, DAT-mediated
      uptake of 6-OHDA recruited the oxidant-induced Kv channel dependent cell death
      pathway present in cortical neurons. Finally, we report that 6-OHDA also
      increased Kv currents in cultured midbrain dopamine neurons and this toxicity was
      blocked with Kv channel antagonists. We conclude that native DAT expression
      accounts for the dopamine neuron specific toxicity of 6-OHDA. Following uptake, 6
      OHDA triggers the oxidant-associated Kv channel-dependent cell death pathway that
      is conserved in non-dopaminergic cortical neurons and midbrain dopamine neurons.

PMID- 17027172
TI  - Analysis of the variation in use-dependent inactivation of high-threshold
      tetrodotoxin-resistant sodium currents recorded from rat sensory neurons.
AB  - This study addressed variation in the use-dependent inactivation (UDI) of high
      threshold tetrodotoxin-resistant Na+ currents (TTX-R currents) and action
      potential firing behavior among acutely isolated rat dorsal root ganglion (DRG)
      cells. UDI was quantified as the percent decrease in current amplitude caused by
      increasing the current activation rate from 0.1-1.0 Hz for 20 s. TTX-R current
      UDI varied from 6% to 66% among 122 DRG cells examined, suggesting the existence
      of two or more levels of UDI. The voltage-dependency of the TTX-R currents was
      consistent with Na(V)1.8, regardless of UDI. However, TTX-R currents with more
      UDI had a more negative voltage-dependency of inactivation, a greater tendency to
      enter slow inactivation, and a slower recovery rate from slow inactivation,
      compared with those with less UDI. TTX-R currents with more UDI ran down faster
      than those with less UDI. However, UDI itself changed little over time,
      regardless of the initial UDI level observed in a particular DRG cell. Together,
      these two observations suggest that individual DRG cells did not express mixtures
      of TTX-R channels that varied regarding UDI. TTX-R current UDI was correlated
      with expression of a low-threshold A-current and whole-cell capacitance,
      suggesting that it varied among different nociceptor types. Whole-cell inward
      currents (WCI-currents), recorded without channel blockers, also exhibited UDI.
      WCI-current UDI varied similarly to TTX-R current UDI in magnitude, and relative
      to whole-cell capacitance and A-current expression, suggesting that the WCI
      currents were carried predominantly by TTX-R channels. DRG cells with more WCI
      current UDI exhibited a greater decrease in action potential amplitude and
      number, and a greater increase in action potential threshold over seven ramp
      depolarizations, compared with DRG cells with less WCI-current UDI. Variation in
      UDI of Na(V)1.8 channels expressed by different nociceptor types could contribute
      to shaping their individual firing patterns in response to noxious stimuli.

PMID- 17027173
TI  - Multisensory processing via early cortical stages: Connections of the primary
      auditory cortical field with other sensory systems.
AB  - It is still a popular view that primary sensory cortices are unimodal, but recent
      physiological studies have shown that under certain behavioral conditions primary
      sensory cortices can also be activated by multiple other modalities. Here, we
      investigate the anatomical substrate, which may underlie multisensory processes
      at the level of the primary auditory cortex (field AI), and which may, in turn,
      enable AI to influence other sensory systems. We approached this issue by means
      of the axonal transport of the sensitive bidirectional neuronal tracer
      fluorescein-labeled dextran which was injected into AI of Mongolian gerbils
      (Meriones unguiculatus). Of the total number of retrogradely labeled cell bodies
      (i.e. cells of origin of direct projections to AI) found in non-auditory sensory
      and multisensory brain areas, approximately 40% were in cortical areas and 60% in
      subcortical structures. Of the cell bodies in the cortical areas about 82% were
      located in multisensory cortex, viz., the dorsoposterior and ventroposterior,
      posterior parietal cortex, the claustrum, and the endopiriform nucleus, 10% were
      located in the primary somatosensory cortex (hindlimb and trunk region), and 8%
      in secondary visual cortex. The cortical regions with retrogradely labeled cells
      also contained anterogradely labeled axons and their terminations, i.e. they are
      also target areas of direct projections from AI. In addition, the primary
      olfactory cortex was identified as a target area of projections from AI. The
      laminar pattern of corticocortical connections suggests that AI receives
      primarily cortical feedback-type inputs and projects in a feedforward manner to
      its target areas. Of the labeled cell bodies in the subcortical structures,
      approximately 90% were located in multisensory thalamic, 4% in visual thalamic,
      and 6% in multisensory lower brainstem structures. At subcortical levels, we
      observed a similar correspondence of retrogradely labeled cells and anterogradely
      labeled axons and terminals in visual (posterior limitans thalamic nucleus) and
      multisensory thalamic nuclei (dorsal and medial division of the medial geniculate
      body, suprageniculate nucleus, posterior thalamic cell group, zona incerta), and
      in the multisensory nucleus of the brachium of the inferior colliculus.
      Retrograde, but not anterograde, labeling was found in the multisensory pontine
      reticular formation, particularly in the reticulotegmental nucleus of the pons.
      Conversely, anterograde, but no retrograde, labeling was found in the visual
      laterodorsal and lateroposterior thalamic nuclei, in the multisensory
      peripeduncular, posterior intralaminar, and reticular thalamic nuclei, as well as
      in the multisensory superior and pericentral inferior colliculi (including
      cuneiform and sagulum nucleus), pontine nuclei, and periaqueductal gray. Our
      study supports the notion that AI is not merely involved in the analysis of
      auditory stimulus properties but also in processing of other sensory and
      multisensory information. Since AI is directly connected to other primary sensory
      cortices (viz. the somatosensory and olfactory ones) multisensory information is
      probably also processed in these cortices. This suggests more generally, that
      primary sensory cortices may not be unimodal.

PMID- 17027174
TI  - Stress dysfunctions as a unifying paradigm for illness: repairing relationships
      instead of individuals as a new gateway for medicine.
AB  - Stress has been implicated as a risk factor for most diseases, but a mechanistic
      explanation behind such associations remains elusive. As emergent responses to
      stress, adaptations range from acute responses where extant system capabilities
      mitigate current stress, to longer-term responses where system plasticity buffers
      against future stress. The long compendium of human ailments manifests through a
      much shorter set of symptoms that may operate through the stress axis. We propose
      a unifying ontology for human illnesses that classifies stress dysfunctions
      according to types of Darwinian dysfunction - inadequate response with adequate
      adaptation, inadequate adaptation, inappropriate adaptation, and epiphenomena of
      adaptation. Examples include cancer as a bystander effect of increased biologic
      plasticity in response to stress, and infectious illness as a manifestation of
      mutually escalating stress in an otherwise commensal relationship between hosts
      and microbes. We explore the contributing role of man-made stresses that have
      emerged as humans increasingly remodel their environment. Examples include
      biologic decompensation associated with reliance on technology to buffer stress,
      and behavioral stress caused by the dislocation of kin networks that promotes
      illegitimate signaling. Dysfunctional relationships engender stress not only
      among humans, but also among individual organs; heart failure, renal failure, and
      carotid stenosis may represent examples of such conditions. If stress dysfunction
      is the Occam's razor of human illnesses, and derangements in biologic
      relationships induce stress dysfunctions, then the study of relationships - an
      incarnation of systems biology - may represent a new gateway for medicine.

PMID- 17027175
TI  - Analysis of the potential of retroviral gene vectors produced on yeast
      intracellular membranes.

PMID- 17027176
TI  - Possible magnetic multifunctional nanoplatforms in medicine.
AB  - Recently, magnetic nanoparticles have attracted attention because of their
      potential in biomedicine. They can be applied to special medical techniques, such
      as separation, immunoassay, magnetic resonance imaging (MRI), drug delivery, and
      hyperthermia, and so on. But these nanoparticles only have one or two kinds of
      functions and cannot realize multipurpose. Therefore, we propose that it is need
      to constitute magnetic multifunctional nanoplatforms, which not only have
      delivery property of gene vector and drug carrier, but also have heating property
      of thermseeds in the alternative magnetic field. Recent trials have proved that
      gene therapy combined with chemotherapy and hyperthermia achieves better results
      than single therapy strategy. But this is difficult in clinical practice. With
      the development of the magnetic multifunctional nanoplatforms, the combined
      treatment is feasible in clinical practice. This nanoplatforms is versatile, and
      can be applied to wide fields. The use of magnetic multifunctional nanoplatforms
      will further improve medical techniques.

PMID- 17027177
TI  - Identification of staphylococcal cassette chromosome mec encoding methicillin
      resistance in Staphylococcus aureus isolates at Charles Nicolle Hospital of
      Tunis.
AB  - Staphylococcal cassette chromosome is a mobile element that carries the gene mecA
      mediating the methicillin resistance in staphylococci. In Staphylococcus aureus
      five types of SCCmec have been described, which differs in size and genetic
      composition among strains. SCCmec typing of 34 non redundant methicillin
      resistant S. aureus (MRSA) recovered in 2004 at Charles Nicolle Hospital of Tunis
      was carried out. The isolates were identified by conventional methods.
      Methicillin resistance was detected by oxacillin and cefoxitin disks and
      confirmed by mecA PCR. The SCCmec complex types were determined by using PCR
      which amplify a sequence overlapping the right SCCmec chromosome junction.
      Strains were recovered mainly from cutaneous pus (61.7%) and blood cultures
      (17.64%). They were isolated from different wards: medicine (53.1%) especially
      from dermatology (41.2%); surgery (40.6%) and pediatrics (3.1%). Only two strains
      were community-acquired MRSA. Two strains (5.9%) were harboring SCCmec type I;
      five (14.7%) SCCmec type II and 27 (79.4%) SCCmec type III. The two community
      acquired MRSA were harboring type II and III SCCmec, usually found in hospital
      acquired MRSA. Our findings indicate that there are only three SCCmec types at
      Charles Nicolle Hospital. However, the existence of SCCmec types II and III in
      community incite us to investigate more community-acquired MRSA.

PMID- 17027178
TI  - Dynamics of Puumala virus infection in bank voles in Ardennes department
      (France).
AB  - The hantaviruses (genus Hantavirus, family Bunyaviridae) include human pathogens
      and occur worldwide. In Western and Central Europe, the predominant serotype is
      Puumala (PUU) virus, which causes epidemic nephropathy. Voles are considered to
      be the main reservoir and the vector of PUU virus. A total of 719 rodents (mainly
      Clethrionomys glareolus, Apodemus sp.) trapped by capture-mark-recapture (CMR) in
      four sites in Ardennes department (France) between April 2004 and October 2005
      were tested for the presence of PUU virus antibodies by enzyme-linked
      immunosorbent assay (ELISA). The predominant species, C. glareolus (86.5% [622 of
      719]), also had the highest antibody prevalence (37.6% [291 of 773]). In C.
      glareolus, the antibody prevalence rate increased with age (weight) in site A, B
      and D, reaching more than 50% in the heaviest weight, and suggesting that
      horizontal infection may be important.

PMID- 17027179
TI  - [Use of BioRad plating agar MRSASelect for the daily detection of methicillin
      resistant staphylococci isolated from samples taken from blood culture bottles].
AB  - Within a medium size general biology laboratory, it is not always easy to set up
      rapid methods for detection of methicillin-resistant staphylococci (detection of
      the mecA gene or PLP2a). Since we already use BioRad chromogenic plating agar
      MRSASelect for the detection of carriers of methicillin resistant Staphylococcus
      aureus, we wanted to test its use on samples taken from blood culture bottles.
      Between December 2004 and October 2005, all the blood bottle cultures that
      detected positive by direct examination for Gram positive cocci and suspected to
      be staphylococci, that is 45 pairs of blood cultures and 3 joint aspirations,
      were inoculated on quarter plates of both MRSASelect and standard non-selective
      agar. After culture, they were screened by the disc method. No mismatch was
      observed between the cultures themselves or the highlighting of methicillin
      resistance in either Staphylococcus aureus isolates or for coagulase-negative
      staphylococci, regardless of species. Furthermore, the red colour of
      Staphylococcus aureus on the medium allowed visualisation of the colonies after
      only about ten hours incubation, thus giving the clinician rapid warning of
      suspected methicillin resistant Staphylococcus aureus. In addition, in
      polymicrobial cultures the different colour of the colonies of Staphylococcus
      aureus (red) and coagulase-negative staphylococci (white) is extremely useful.

PMID- 17027180
TI  - [Caenorhabditis elegans: in vivo study model of bacterial virulence].
AB  - The nematode Caenorhabditis elegans presents many advantages as a model system.
      The worm has recently emerged as a potentially useful tool for the study of host
      pathogen interactions. This paper presents advantages and inconveniences of this
      model, the variety of bacterial pathogens studied, and its use to monitor
      virulence of Extraintestinal Escherichia coli strains.

PMID- 17027181
TI  - [Contribution of PCR for detection of Mycobacterium tuberculosis complex in
      respiratory and nonrespiratory specimens].
AB  - AIM OF THE STUDY: To evaluate the sensitivity of PCR versus culture of complex
      tuberculosis mycobacteria and to determine the delay between PCR results and
      identification of mycobacteria in culture. MATERIALS AND METHODS: Ninety-nine
      pulmonary and 66 extrapulmonary specimens were analyzed. Samples were inoculated
      on liquid (MGIT, Bactec) and solid media (Coletsos) and respectively incubated 6
      and 12 weeks. Identification was performed by reverse hybridization of PCR
      products to their complementary probes immobilized on membrane strips (Genotype
      MTBC, HAIN). Specimens DNA detection was realized by PCR (Cobas Amplicor
      Mycobacterium tuberculosis test, Roche). RESULTS: Sensitivity of PCR for acid
      fast bacilli smear positive pulmonary (50/50) and extrapulmonary (7/7) specimens
      was 100%. Delay between PCR result and identification was 11 days for pulmonary
      specimens and 8 days for extrapulmonary specimens. Sensitivity of PCR for smear
      negative samples was, respectively, of 78.7% (37/47) and 51.8% (29/56) for
      pulmonary and extrapulmonary specimens. In case of PCR positive result of a smear
      negative sample, a gap of respectively 13 and 12 days was obtained for pulmonary
      and extrapulmonary specimens compared to identification. CONCLUSION: Positive PCR
      result for respiratory specimens allows a gap of 11 to 13 days in diagnosis in
      comparison with identification of mycobacteria in culture.

PMID- 17027182
TI  - [Uncomplicated urinary tract infections, what about fosfomycin and nitrofurantoin
      in 2006?].
AB  - Since 2000 to 2005 we assessed the prevalence of antimicrobial resistance among
      uropathogens causing acute uncomplicated urinary tract infections (UTI). A total
      of 19 618 bacteria were studied, fosfomycin, fluoroquinolones, nitrofurantoin
      were in vitro the most potent drugs with more than 80% of susceptibility. If we
      compare year 2000 to 2005 we observed a significant decrease of susceptibility
      for fluoroquinolones. For the same point of comparison, fosfomycin and
      nitrofurantoin showed a favourable evolution. Rationale and prudent use of
      antibiotics must now moved us to prescribe parsimoniously fluoroquinolones
      especially for some indications such as uncomplicated UTI though there are some
      others "old antibiotics" with a role may be underestimated for this specific
      indication.

PMID- 17027183
TI  - [Comparative susceptibility evolution in Escherichia coli from urinary tract
      infections in outpatients and inpatients at Perpignan hospital in 2002 and 2004].
AB  - The medical emergency ward makes a link between outpatients and hospitalized
      ones, so we can study community bacterial ecology. The antibiotic susceptibility
      in Escherichia coli strains isolated from urinary tract infections (UTI) of
      patients consulting at emergency ward of our hospital in 2002 and 2004 was
      determined and compared with the susceptibility of the same strains isolated from
      UTI of hospitalized patients on the same period. The antibiotic susceptibility
      was performed with Microscan (Dade Behring). All bacteria were tested against the
      following antimicrobial agents: amoxicilline (Amx), l'amoxicilline+clavulanic
      acid (AMC), nalidixic acid (NA), ciprofloxacine (Cip), cotrimoxazole (SXT),
      nitrofurantoin (Ft). Susceptibility in E. coli strains isolated from outpatients
      vary from 58 to 54% for Amx, from 88 to 83% for NA, from 96 to 89% for Cip, from
      82 to 79% for SXT, from 94 to 96% for Ft and remains at 60% for AMC from 2002 to
      2004. Susceptibility in E. coli strains isolated from hospitalized patients vary
      from 52 to 47% for Amx, 55 to 53% for AMC, from 79 to 70% for NA, from 87 to 79%
      for Cip, from 74 to 69% for SXT, from 93 to 92% for Ft. Susceptibility in E. coli
      strains isolated in the community from UTI outpatients is decreasing and it
      becomes worrying particularly concerning the fluoroquinolones, therefore empiric
      treatment of pyelonephritis by fluoroquinolones must be assessed again.

PMID- 17027184
TI  - [Direct and fast detection of methicillin resistant Staphylococcus aureus
      carriage by automated nucleic acid extraction and real time PCR].
AB  - We have developed a real time PCR assay for methicillin resistant Staphylococcus
      aureus (MRSA) screening able to provide a result in less than 3 h. The PCR
      amplifies a 184 bp fragment corresponding to the junction area between mecA and
      orfX genes that allows specific identification of MRSA in a nonsterile specimen.
      1481 nasal swabs taken from geriatrics, dialysis and intensive care patients were
      compared with traditional bacteriology. A short centrifugation, preliminary to
      the extraction, with "SETS" system allows a recovery of the sample. The automated
      DNA extraction is carried out by the MagNA Pure LC and the PCR by the
      LightCycler. The agreement between the two methods is 97.7%. A study of
      sensitivity and specificity on 1111 samples respectively gives 75 and 98% for the
      real time PCR and, 64 and 99% for the culture. The strategy of fast and effective
      tracking that we propose is of an undeniable contribution in the fight against
      the MRSA infections.

PMID- 17027185
TI  - [HIV controllers: a homogeneous group of HIV-1 infected patients with a
      spontaneous control of viral replication].
AB  - We identified a group of chronically HIV-1-infected patients in whom viral
      replication is spontaneously controlled without antiretroviral treatment. These
      patients account for less than 1% of HIV-infected patients. They are defined
      according to a virological definition: plasma viral load less than 400 copies
      RNA/ml in more than 90% of the samples tested and HIV positive serology known for
      more than 10 years. They should never have received antiretroviral therapy. The
      CD4 T cell count is not taken into account, which differenciate these patients
      from long-term non progressors. Fifteen patients HIV controllers have been
      studied in a preliminary work with two main results: i) the demonstration of a
      strong HIV-specific CD8 immune response and ii) the amount of viral DNA in PBMCs
      is very low and stable along the time. The aim of the ANRS EP36 study group is to
      precize the immunological and virological characteristics of these patients.
      First data seem to confirm an essential role of CD8 T cells to control viral
      replication, the absence of defective virus, and a normal susceptibility of the
      CD4 T cells from these patients to the infection with various HIV strains. This
      group of patients is homogeneous and its study supports physiopathological
      studies. To go further, a national survey of these patients has been set up to
      allow future study.

PMID- 17027186
TI  - Streptococcus pneumoniae thoracic empyema in children: rapid diagnosis by using
      the Binax NOW immunochromatographic membrane test in pleural fluids.
AB  - AIM: To evaluate an immunochromatographic membrane test for Streptococcus
      pneumoniae antigen (Binax NOW, Inverness medical France) applied to pleural fluid
      samples. METHODS: Binax NOW was applied to the pleural fluids of 69 children with
      thoracic empyema, in comparison with conventional culture and molecular
      techniques. RESULTS: Binax NOW was positive on all 15 pleural fluid samples that
      yielded S. pneumoniae in culture, on two samples that yielded S. oralis and S.
      salivarius in culture and on 34 culture-negative samples. Fifteen of these 34
      culture-negative samples were retrospectively tested by PCR methods, and 14 were
      shown to contain S. pneumoniae DNA. Thus, S. pneumoniae was identified by culture
      in 22% of samples and by Binax NOW in 69% of samples. CONCLUSION: Binax NOW may
      thus be useful for rapid diagnosis of S. pneumoniae thoracic empyema.

PMID- 17027187
TI  - [Treatment of localised lung cancer].
AB  - This paper focuses on stage I, II and IIIA non-small cell lung cancer treatable
      with local treatment. It addresses five questions raised by strategies combining
      local treatments with chemotherapy. Even if chemotherapy increases resectability
      of stage III disease, the chemotherapy-surgery combination has not been
      demonstrated to increase survival compared to the standard chemo-radiation
      treatment. The results of the study by Van Meerbeeck do not support this
      hypothesis. Does surgery, added to chemo-radiotherapy, improve the outcome in
      stage IIIAN2 disease? This was the question addressed by the study by K. Albain.
      There is probably not clear cut answer. However, the trimodality strategy might
      be interesting in patients undergoing a lobectomy and might have a negative
      impact when a pneumonectomy has been performed. In patients with a non
      resectable/inoperable cancer treated with standard chemoradiation, the
      concomitant strategy has been shown to be superior to sequential treatment.
      However, due to acute toxicity, it should be delivered to selected patients, who
      still need to be better defined. The chemotherapy-surgery combination is becoming
      standard (in stage II disease) and most cooperative groups will probably stand in
      favour of it in 2006. The best respective timing for chemotherapy and surgery is
      still debated. There are many advantages in favour of preoperative chemotherapy,
      including better feasibility and the higher proportion of patients who can
      benefit. However, there is no statistically reliable demonstration of such
      superiority.

PMID- 17027188
TI  - [Hepatic steatosis: an emerging cause of cirrhosis in HIV patients].
AB  - Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy
      (ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly
      understood. We report two cases of rapid evolution of disseminated macrovacuolar
      steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor
      intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS
      antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled
      with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy
      showed a disseminated macrovacuolar steatosis (>80%). The patient had then
      cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two
      years later, and HIV was controlled by a new line of ART. It showed a regression
      of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis.
      Patient 2 had a long history of HIV infection. He also had an uncontrolled
      dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV
      infection and elevated liver enzymes. The biopsy showed a major macrovacuolar
      steatosis (>80%). The second biopsy was realised 6 years after and showed the
      same steatosis and signs of cirrhosis. The HIV infection was then under control.
      Observations reported here show a rapid evolution of liver steatosis to cirrhosis
      in HIV positive / HCV negative patients, despite the control of HIV infection.
      The implication of HAART remains unclear. In the era of HAART, liver steatosis
      can rapidly evoluate to cirrhosis without any risk factor except ART.

PMID- 17027189
TI  - [Evaluation of four immunoenzymatic tests for detecting Clostridium difficile
      toxins A and B].
AB  - Four immunoenzymatic tests for detecting Clostridium difficile toxins A and B
      were studied: two rapid tests (Tox A/B QUIK CHEK-Techlab and NoviView Toxine-A
      Hiss diagnostics) and two Elisa tests (C. difficile TOX A/B II -Techlab and Toxin
      A+B Elisa Test, Novitec-Hiss diagnostics). The results were compared to those
      obtained with ImmunoCard Tox A+B -ICTAB (Meridian), C. difficile Toxine A (Oxoid)
      for rapid test and Elisa Premier A+B Meridian for Elisa. A total of 41 stools and
      16 isolates were studied with rapid tests. On stools, the sensitivity and
      specificity of QUIK CHEK test was 94.1% and 100% respectively compared to the
      test ICTAB. On the isolates, sensitivity and specificity was 100%. With the
      Noviview test, the sensitivity on stools and isolates was respectively 88.2 and
      85.7% and the specificity was 100% compared to Oxoid. A total of 38 stools were
      studied with Elisa tests. With Techlab test compared to the test Premier,
      sensitivity and specificity was 100%. The Novitec test gave five false negative
      reactions with consequently a sensitivity of 70.6%.

PMID- 17027190
TI  - Resistance to antibiotics in clinical isolates of Pseudomonas aeruginosa.
AB  - OBJECTIVES: To analyse the global resistance to some antibiotics used to treat
      nosocomial infections by Pseudomonas aeruginosa, specially to carbapenems, and
      its relationship with the presence of carbapenemases, OXA, VIM and IMP. METHODS:
      The study included 229 P. aeruginosa isolates from a Hospital in Northern Spain
      (year 2002). Susceptibility to antimicrobial agents was determined by the
      analysis of the MIC. Genetic typing was carried out by RAPD-PCR fingerprinting
      with primer ERIC-2. Genetic experiments to detect class-1 integrons were
      performed by PCR with primers 5'CS and 3'CS. Detection of carbapenemases was done
      by phenotypic (Hodge test and DDST) and genotypic methods (PCR with primers for
      imp, vim1, vim2 and oxa40 genes). RESULTS: 23.9% of isolates were resistant to
      ceftazidime, 35.9% to cefotaxime, 5.3% to amikacin, 54.9% to gentamicin, 14.6% to
      imipenem and 6.6% to meropenem. Isolates resistant to imipenem (33) were
      furtherly tested. Genetic typing didn't show clonal relatedness among the most of
      the isolates. Class-1 integrons were present in most isolates (sizes 600-1700
      bp). Phenotypic methods for carbapenemases showed 5 positive isolates. Genotypic
      methods showed the presence of two isolates with the oxa40 gene. CONCLUSIONS:
      Meropenem, amikacin and imipenem were the most active agents to treat infections
      caused by Pseudomonas aeruginosa. In our study, the presence of carbapenemase
      enzymes wasn't high. Phenotypic tests cannot be considered as accurate screening
      tool to detect carbapenemases. This is the fist report of the oxa40 gene in
      Pseudomonas aeruginosa isolates.

PMID- 17027191
TI  - [Recurrence of hepatitis C virus (HCV) infection after liver transplantation for
      HCV-related disease: host factors and viral factors implicated in the occurrence
      and the severity of HCV recurrence].
AB  - Cirrhosis due to chronic infection by hepatitis C virus (HCV), associated or not
      to a primary hepatocarcinoma, has become the first indication of liver
      transplantation. Graft reinfection by HCV is considered to be systematic while
      its prognosis is variable from one patient to another. A better knowledge of
      factors implicated in the occurrence and severity of hepatitis C recurrence is
      crucial in order to make optimal patients' monitoring. This article aims to
      present available data in this field, clarifying the role of viral factors (viral
      load, genotype, evolution of viral quasispecies) and host-related factors (immune
      response) which could take part in the development of hepatitis C recurrence.

PMID- 17027192
TI  - [Automated RNA amplification for the rapid identification of Mycobacterium
      tuberculosis complex in respiratory specimens].
AB  - Rapid and sensitive detection of Mycobacterium tuberculosis complex (MTB)
      directly on clinical respiratory specimens is essential for a correct management
      of patients suspected of tuberculosis. For this purpose PCR-based kits are
      available to detect MTB in respiratory specimen but most of them need at least 4
      hours to be completed. New methods, based on TRC method (TRC: Transcription
      Reverse transcription Concerted--TRCRapid M. Tuberculosis--Tosoh Bioscience,
      Tokyo, Japon) and dedicated monitor have been developed. A new kit (TRC Rapid M.
      tuberculosis and Real-time monitor TRCRapid-160, Tosoh Corporation, Japan)
      enabling one step amplification and real-time detection of MTB 16S rRNA by a
      combination of intercalative dye oxazole yellow-linked DNA probe and isothermal
      RNA amplification directly on respiratory specimens has been tested in our
      laboratory. 319 respiratory specimens were tested in this preliminary study and
      results were compared to smear and culture. Fourteen had a positive culture for
      MTB. Among theses samples, smear was positive in 11 cases (78.6%) and TRC process
      was positive in 8 cases (57.1%). Overall sensitivity of TRC compared to smear
      positive samples is 73%. Theses first results demonstrated that a rapid
      identification of MTB was possible (less than 2 processing hours for 14 specimens
      and about 1 hour for 1 specimen) in most cases of smear positive samples using
      ready to use reagents for real time detection of MTB rRNA in clinical samples.
      New pretreatment and extraction reagents kits to increase the stability of the
      sputum RNA and the extraction efficiency are now tested in our laboratory.

PMID- 17027193
TI  - [Bacterial DNA alteration by plasma generated atomic nitrogen. Real-time PCR
      detection contribution].
AB  - AIMS: Bacterial sterilization by the technology of plasma in post-discharge shows
      a growing interest. The main appeal of this new process resides in its action at
      dry and low temperature (60 degrees C). This technology would be therefore useful
      for the complex medical equipment, sensitive to the oxidization, humidity and/or
      requiring a temperature lower than 60 degrees C. The objective of this survey is
      to demonstrate the activity of an atomic flux emanating a plasma of pure
      molecular nitrogen on the bacterial DNA: does the plasma of nitrogen damage the
      genetic material? MATERIALS AND METHODS: The bacteria tested (Bacillus
      stearothermophilus, Staphylococcus aureus MRSA and Helicobacter pylori) are
      cultivated on suitable agar, and the bacterial DNA is extracted from every CFU by
      the technique of the columns (High Pure PCR Template, Roche). Every quantity of
      DNA extracted is diluted in 1 ml pure water. Then, 50 microl of each of these
      solutions of DNA are laid down in sterile Nunclon's plates holes, which undergo
      an advanced emptiness cycle during 60 minutes. The DNA residues will be then
      introduced during 40 minutes in a plasma sterilization surrounding wall
      (Plasmalyse), Satelec) where the debit of nitrogen, the pressure and the
      temperature are adjusted respectively to 1 L x min(-1), 5 Torrs and 60 degrees C.
      The DNA so ''plasmalyse'', is recovered then by aspiration in 500 mul pure water
      and processed to undergo an amplification/detection by Real-Time PCR
      (LightCycler2.0, Roche). The DNA ''plasmalyse'' will be compared to the intact
      DNA control(1), to the DNA control control(2) having undergone the cycle of
      emptiness solely, as well as to the DNA control(3) solely heated to 60 degrees C
      during 40 min. RESULTS: The amplification curves demonstrated that the only
      advanced emptiness and the only heat don't have any activity on the bacterial
      DNA. On the other hand, the DNA ''plasmalyse'' shows a deterioration of the
      amplified sequences. CONCLUSION: The genomic bacterial DNA, once extracted, is
      damaged by the gaseous flux of nitrogen plasma. A new sterilization process of
      the medical material will presumably impose itself in medium-term.

PMID- 17027194
TI  - Evaluation by Q-RTPCR of the efficacy of ribavirin complexed with beta
      cyclodextrin against measles virus in a mouse encephalitis model.
AB  - The objective of this work was to study the antiviral activity of ribavirin on
      measles encephalitis infection when using cyclodextrins as carriers. The use of
      cyclic oligosaccharides can promote the activity of many drugs and the benefit of
      the association of ribavirin with beta-cyclodextrin has already been demonstrated
      in vitro. Intracranial inoculation of the rodent adapted neurovirulent CAM/RB
      strain of measles virus induces encephalitis in CBA/ca mice. The antiviral
      activity of the complex ribavirin/beta-cyclodextrin at molar ratio 1:1 has been
      evaluated in vivo in the above encephalitis model. CBA/ca mice were treated with
      daily intraperitoneal injection of ribavirin (40 mg/kg) with or without beta
      cyclodextrin. The viral load in the brain of mice was quantified by real-time
      Reverse transcription-Polymerase chain reaction. Treatment of mice by the complex
      ribavirin/beta-cyclodextrin (1:1) by intraperitoneal route decreases the viral
      load in the brain of 1.1 and 0.7 log(10) Eq copies x mL(-1) compared to
      distillated water and ribavirin treatment, respectively. At the same time, free
      ribavirin injection shows a negligible difference compared to treatment by
      distillated water.

PMID- 17027195
TI  - Recent and future therapeutic advances in the management of HIV infection.
AB  - Human immunodeficiency virus (HIV) infection is a worldwide pandemic that remains
      a major health and socio-epidemiological problem at the beginning of the 21st
      century, including in developed countries. In 2006, 10 years after the
      introduction of highly active antiretroviral therapy (HAART), therapeutic needs
      in HIV are different from what they were a decade ago. Physicians now handle more
      than 20 different molecules, all active against HIV virus. However, they still
      need safe, tolerable and simple regimens in order to improve patient's compliance
      to therapy, as well as more potent drugs in cases of multi-resistant viral
      strains. Our understanding of HIV infection and its medical management has
      improved and will certainly continue to evolve. We are currently taking benefit
      from the elaboration and evaluation of various new therapeutic concepts and
      promising future medical approaches based on already 20 years experience in the
      field of HIV management, as well as on the rapidly expanding pharmaceutical
      development and researches in this domain. Nevertheless, the majority of these
      new therapeutic strategies are still to be further evaluated, and their practical
      application is awaiting the results of numerous ongoing clinical trials.

PMID- 17027196
TI  - [Simultaneous detection by multiplex PCR of atypical bacterial pathogens involved
      in infections of respiratory tract. Is it useful for the microbiological
      diagnosis of respiratory infections].
AB  - The aim was to evaluate the "strategical place" of the new commercial test
      Chlamylege (Argene-Biosoft-France) which allows the simultaneous detection in
      respiratory samples of Chlamydophila pneumoniae, Mycoplasma pneumoniae and most
      Legionella species using a PCR multiplex. 41 patients with an atypical pneumonia
      were included, all standard procedures of diagnosis were done and in addition the
      chamylege test. A pathogen was identified in 12 patients, an other microorganisms
      than the 3 targeted by our study was found in 8 patients. 4 positive PCR were
      obtained, 3 with M. pneumoniae and 1 with Legionella pneumophila 1. That means
      that for 29 patients no aetiology was found. Among them 23 clearly improved under
      antibiotic treatment. Though that PCR multiplex is an attractive test, easy to
      perform, sensitive, specific and convenient, we need further studies to approach
      the place of this PCR test in the diagnosis of multifaceted atypical pneumonia.
      We also need to know if the cost associated with the microbiological diagnosis
      (culture, serology, immunofluorescence, urinary antigen test, PCR...) for
      atypical pneumonia worth value? An algorithm as to be drawn to determine the
      value of intensive microbiological investigation. An other point to discuss, may
      be this kind of rapid and multiplex PCR technique could lead to spare the use of
      some antibiotics.

PMID- 17027197
TI  - Prevalence of agr specificity groups among methicilin resistant Staphylococcus
      aureus circulating at Charles Nicolle hospital of Tunis.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen with
      many clinical aspects. In S. aureus, the accessory gene regulator (agr) globally
      controls the production of virulence factors. There are four agr groups. Our
      study was done to define the agr specificity of MRSA circulating at Charles
      Nicolle hospital and to investigate a possible relationship between agr groups
      and human disease types. From January 2004 to June 2005, a total of 57 MRSA
      isolated from individual hospitalized patients were collected, representing 12%
      of the total S. aureus isolates. The isolates were identified by conventional
      methods. Methicillin resistance was detected by oxacillin and cefoxitin disks and
      confirmed by the amplification of mecA gene by PCR. The agr groups were
      identified by multiplex PCR. All the strains were recovered from different wards:
      medicine (57.8%) especially from dermatology (56.2%), surgery (28%) and
      pediatrics (7%). Cutaneous pus (36.84%) and blood culture (35.08%) represented
      the main specimens. The agr groups were distributed as follow nine (15.7%)
      belonged to group I, two (3.5%) belonged to group II and 23 (40.3%) belonged to
      group III. For 23 strains, the agr group was not identified. A relationship
      between agr group and type of disease was observed: agr group III strains were
      associated with non invasive infections (P=0.02) and agr group I strains with
      invasive infections especially bacteremia (P=0.002).

PMID- 17027198
TI  - [Optimisation of retrospective diagnosis of cytomegalovirus congenital infection
      from dried blood spots].
AB  - Out of the 90% of cytomegalovirus (CMV) congenitally infected children that are
      asymptomatic at birth, 5 to 15% will later develop complications, mainly
      neurodevelopmental defects and/or deafness. Unfortunately, after the first 2
      weeks of life, usual diagnostic techniques for CMV detection (viral culture and
      serology) are useless to differentiate congenital infection from post-natal
      acquired infection, whereas detection of viral DNA from dried blood spots (DBS;
      Guthrie cards), systematically collected from all newborns in the first days of
      life, has been described for late diagnosis of CMV congenital infection. The aim
      of our study was to choose and optimise a viral DNA extraction method from DBS
      and to study if CMV DNA detection is reliable when DBS are stored for 1 year at
      room temperature or 2 months at 37 degrees C. 10 reference cards (blood collected
      from CMV seronegative newborns (IgG/IgM negative) were "infected" with serial
      dilutions of virus and spotted on Guthrie cards) were tested. 3 extraction
      methods were evaluated, products of PCR were analyzes by agarose gel
      electrophoresis and quantification of CMV from DBS was also performed. Analysis
      of the results obtained from reference cards showed higher sensitivity of
      phenol/chloroform extraction following treatment with proteinase K, compared to
      heat extraction in cell culture medium or extraction with a commercial kit. We
      did not observe quantitative loss of viral DNA after 1 year storage at room
      temperature. CMV DNA detection from Guthrie cards could become a very useful tool
      for retrospective diagnosis of congenital CMV infection when sequelae are
      diagnosed in the first years of life. We are pursuing this study with DBS from
      congenitally infected children.

PMID- 17027199
TI  - Phylogenetic relationships and gene expression pattern of three different
      cathepsin L (Ctsl) isoforms in zebrafish: Ctsla is the putative yolk processing
      enzyme.
AB  - Certain cysteine proteases, such as cathepsin L (Ctsl), have been involved in
      yolk processing mechanisms in oocytes and embryos of lower vertebrates. In
      zebrafish (Danio rerio), three different ctsl genes, ctsla, ctslb and ctslc, have
      been found in the genome, but their pattern of expression, as well as information
      on which the encoded enzymes are potentially involved in yolk absorption during
      embryogenesis, is unknown. Here, phylogenetic and gene structure analysis
      revealed that zebrafish ctsla and ctslb genes are similar, showing a highly
      conserved structure in comparison with human ctsl, while ctslc presents different
      exon organization together with an earlier evolution. Thus, ctslc appears to be
      evolved from a common ancestral ctsl-like gene, possibly through an early
      duplication event, whereas ctsla and ctslb may be originated from a second
      duplication mechanism. Zebrafish ctsla, ctslb and ctslc also showed different
      patterns of mRNA expression during embryogenesis and in adult tissues. While
      Ctsla transcripts were accumulated in embryos throughout development and in the
      adult ovary, those encoding Ctslb were detected only in embryos around the time
      of hatching as previously reported, and those for Ctslc appeared only in larvae
      and in some adult tissues, but not in the ovary. In zebrafish and killifish
      (Fundulus heteroclitus) embryos, Ctsla mRNA was first detected in blastomers, and
      later in development it was localized in cells of the yolk syncytial layer, an
      embryonic structure involved in yolk absorption. These data therefore suggested
      that Ctsla is most likely the putative protease involved in yolk processing in
      fish embryos, while Ctslc seems not to be required during early embryogenesis in
      zebrafish.

PMID- 17027200
TI  - Introduction for the Gene special issue dedicated to the meeting "Genomic impact
      of eukaryotic transposable elements" at Asilomar.

PMID- 17027201
TI  - DNA damage and repair capacity by comet assay in lymphocytes of white-collar
      active smokers and passive smokers (non- and ex-smokers) at workplace.
AB  - The comet assay has been widely used to quantify DNA damage in isolated
      lymphocytes from subjects exposed to several environmental or occupational
      substances, especially for estimation of oxidative damage in the DNA, which is
      well-known to be induced by tobacco smoke. Passive smoking or environmental
      tobacco smoke (ETS) has been included among those substances that cause cancer
      with sufficient evidence in humans. In this study, we analyzed, by the alkaline
      version of comet assay, the lymphocyte DNA damage of white-collar active smokers
      and non- and ex-smokers exposed to ETS at the workplace. We investigated basal
      DNA damage, DNA oxidation by formamidopyrimidine glycosylase (Fpg), the repair
      capacity H2O2-induced DNA damage by kinetics studies and lymphocyte GSH levels,
      the major intracellular defense against exogenous oxidative stress imposed by
      cigarette smoking. Our results indicated high basal DNA damage with clear
      significant correlations with urinary nicotine and cotinine, number of
      cigarettes/day, and an inverse significant correlation with GSH cellular content
      in active smokers. Significant Fpg-sensitive sites were found in smokers (> 85%),
      considerably high but not significant in passive non- and ex-smokers (> 51% and
      37%, respectively). The DNA repair capacity had seriously decreased in non
      smokers > smokers > ex-smokers, while the same damage was repaired in a short
      time in never smokers.

PMID- 17027202
TI  - Early detection and treatment of vesicular adenitis in bulls.
AB  - The objective of this study was to determine whether early detection and
      treatment with tilmicosin would reduce the number of yearling bulls culled due to
      vesicular gland disease at the time of their first semen test. Bulls (n=2207) of
      15 breeds at 17 performance test stations were examined by transrectal palpation
      at 9-12 months of age and assigned to three treatment groups: (1) positive
      treated group, receiving subcutaneous injections of tilmicosin every second day
      for three treatments (2) positive untreated control group, (3) negative untreated
      control group. Transrectal palpation of the glands was done again at a pre-sale
      semen test 28-70 d (mean=42.8 d) after the first examination. Semen was evaluated
      for the presence of pus and/or leukocytes by light microscopy. The proportion of
      bulls with vesiculitis was 4.4% (97/2207). At the pre-sale semen test the number
      of bulls with vesiculitis had decreased to 1.3% (29/2207); however, seven of
      these were new cases that developed after the first examination. Therefore, there
      was a recovery rate of 75/97 (77.3%) in the original group of bulls positive for
      vesiculitis. At the pre-sale test, there was no difference in the proportion of
      bulls with enlarged glands in the positive treated group (15/66) versus the
      positive untreated group (7/31) and no difference in the proportion of bulls with
      leukocytes or pus in their semen samples. The results of this experiment did not
      indicate any advantage in detection and treatment of vesiculitis before a year on
      age due to a high rate of spontaneous recovery.

PMID- 17027203
TI  - Changes in the ovarian dynamics and endocrine profiles in goats treated with a
      progesterone antagonist during the early luteal phase of the estrous cycle.
AB  - The aim of the present study was to determine the physiological role of
      endogenous progesterone in the regulation of ovarian dynamics, gonadotropin and
      progesterone secretion during the early luteal phase in the goat. Cycling Shiba
      goats received subcutaneously a vehicle (control group, n=5) or 50 mg of RU486
      (RU486 group, n=4) daily from 1 to 7 days after ovulation (day 0) determined by
      transrectal ultrasonography. Ovarian dynamics were monitored by the
      ultrasonography and blood samples were collected daily until the subsequent
      ovulation for analysis of progesterone, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) secretion. Blood samples were also collected at 10 min
      intervals for 6 h on day 3 and day 7 for the analysis of pulsatile patterns of LH
      and FSH. The LH pulse frequency was significantly (P<0.05) higher in the RU486
      group than in the control group on day 7 (4.8+/-1.1 pulses/6 h versus 1.2+/-0.4
      pulses/6 h). The shape of the FSH pulses was unclear on day 3 and day 7 in both
      groups and the overall means of FSH concentration for 6 h on day 3 and day 7 were
      not significantly different between the RU486 and the control groups. The pattern
      of daily FSH concentrations showed a wave-like fluctuation in both groups. There
      was no significant difference in the inter-peak intervals of the wave-like
      pattern of daily FSH secretion between the RU486 and the control groups (4.1+/
      0.6 days versus 4.5+/-0.6 days). The maximum diameter of the largest follicle
      that grew from day 1 to day 7 in the RU486 group tended to be greater than that
      in control goats (6.4+/-0.8 mm versus 5.0+/-0.8 mm, P=0.050), whereas no
      significant difference was detected in the size of the corpus luteum and
      progesterone concentrations between the control and RU486 groups on almost all
      days during the treatment period. These results indicate that the rise of the
      progesterone concentration suppresses the pulsatile LH secretion and follicular
      growth, whereas progesterone has no physiological role in the regulation of FSH
      secretion and luteal function during the early luteal phase of the estrous cycle
      in goats.

PMID- 17027204
TI  - Stabilization of protein encapsulated in poly(lactide-co-glycolide) microspheres
      by novel viscous S/W/O/W method.
AB  - In stabilizing proteins during microsphere fabrication, the viscous solid-in
      water-in-oil-in-water (S/W/O/W) method was compared to the conventional multi
      emulsion W/O/W and S/O/W method. Solid proteins lyophilized with cyclodextrin
      derivatives and polyethylene glycol (PEG) pass through an organic solvent phase
      and are then embedded in aqueous microdroplets of first emulsion. Proteins were
      stabilized at the water/organic solvent interface by an internal aqueous phase
      containing viscous polysaccharides, and then can be safely encapsulated without
      degradation. In addition, these microspheres showed a long-term protein release
      followed by nearly zero-order kinetics with minimal initial burst. This means
      that the viscous S/W/O/W method provides a safe strategy for microsphere
      fabrication and has promising properties, involving the preservation of protein
      bioactivity, the inhibition of protein denaturation or agglomeration, and long
      term protein release.

PMID- 17027205
TI  - Doxorubicin skin penetration from monoolein-containing propylene glycol
      formulations.
AB  - Topical chemotherapy with the antineoplastic doxorubicin (DXR) could be an
      alternative to treat skin cancer, however its poor skin penetration often limits
      the efficacy of topical formulations. The aim of this work was to study the
      effect of monoolein (MO), a penetration enhancer, on the in vitro skin permeation
      and retention of DXR. DXR was incorporated in a propylene glycol preparation
      containing 0-20% of MO. DXR release rate and topical delivery were evaluated in
      vitro using acetate cellulose membrane and porcine skin, respectively, mounted in
      a Franz diffusion cell. At 5%, MO did not significantly change DXR release rate,
      but MO concentrations larger than 10% decreased almost twice its release. In
      vitro skin penetration studies showed that the presence of MO in the propylene
      glycol formulations markedly increased DXR presence in the stratum corneum (SC).
      At 5%, MO significantly increased the amount of DXR in the SC already in the
      first hours, attained a maximum in 6h. Comparing propylene glycol formulations
      containing more than 10% MO with that containing 5%, the former took the double
      of the time (12h) to reach the same amount of DXR in the skin, result that is in
      agreement with in vitro release studies. Interesting, despite the fact that MO
      significantly increased the amount of DXR in the SC, drug transdermal delivery
      did not change. These findings suggest a cutaneous delivery of DXR that is an
      important condition for topical treatment of skin tumors. Further in vivo
      experiments can show DXR delivery to deeper skin layers.

PMID- 17027206
TI  - A novel multicompartimental system based on aminated poly(vinyl alcohol)
      microspheres/succinoylated pullulan microspheres for oral delivery of anionic
      drugs.
AB  - Poly(vinyl alcohol) (PVA) microspheres were prepared by dispersion reticulation
      with glutaraldehyde and further aminated. These microspheres were firstly loaded
      with diclofenac (DF) and then entrapped in cellulose acetate butyrate (CAB)
      microcapsules by an o/w solvent evaporation technique for intestinal delivery of
      drug. The encapsulated PVA microspheres due to their low swelling degree in
      intestinal fluids, do not have enough force to produce the disruption of CAB
      shell, therefore different amounts of succinoylated pullulan microspheres (SP-Ms)
      (exchange capacity up to 5.2 meq/g) were co-encapsulated. The SP-Ms do not swell
      in acidic pH, but swell up to 20-times in intestinal fluids causing the rupture
      of CAB shell and facilitating the escape of loaded PVA microspheres.

PMID- 17027207
TI  - Effect of the melt granulation technique on the dissolution characteristics of
      griseofulvin.
AB  - This work describes a melt granulation technique to improve the dissolution
      characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation
      technique is a process by which pharmaceutical powders are efficiently
      agglomerated by a meltable binder. The advantage of this technique compared to a
      conventional granulation is that no water or organic solvents is needed. Because
      there is no drying step, the process is less time consuming and uses less energy
      than wet granulation. Granules were prepared in a lab scale high shear mixer,
      using a jacket temperature of 60 degrees C and an impeller speed of approximately
      20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire
      44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was
      investigated using a half two level-four factor factorial design. The granules
      were characterized using powder XRD, DSC and SEM techniques. A significant
      enhancement in the in vitro dissolution profiles of the granules was observed
      compared to the pure drug and drug excipient physical mixtures. The factorial
      design results indicated that higher drug loading and the presence of HPMC
      reduced the extent of dissolution of the drug, whereas, the presence of starch
      enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation
      matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in
      the granulated formulations. In conclusion, the results of this work suggest that
      melt granulation is a useful technique to enhance the dissolution rate of poorly
      water-soluble drugs, such as, griseofulvin.

PMID- 17027208
TI  - Antispasmodic and relaxant effects of the hidroalcoholic extract of Pimpinella
      anisum (Apiaceae) on rat anococcygeus smooth muscle.
AB  - The present work describes the mechanisms involved in the muscle relaxant effect
      of ethanol:water (40:60, 60:40 and 80:20) aerial parts extracts of Pimpinella
      anisum. Three hidroalcoholic extracts in which the proportion of ethanol was 40%
      (HA(40%)), 60% (HA(60%)) or 80% (HA(80%)) were tested for activity in the rat
      anococcygeus smooth muscle. The three extracts (50 microg/mL) inhibited
      acetylcholine-induced contraction. The extract HA(60%) (5-50 microg/mL)
      concentration dependently relaxed acetylcholine-pre-contracted tissues (31.55+/
      3.56%). Conversely, HA(40%) and HA(80%) did not exert relaxant action. Pre
      incubation of the preparations with N(G)-nitro-L-arginine methyl ester (L-NAME,
      100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 3 microM) and
      oxyhemoglobin (10 microM) reduced the relaxation induced by HA(60%) (percentage
      of relaxation: 6.81+/-1.86%, 13.13+/-5.87% and 2.12+/-1.46%, respectively).
      Neither indomethacin (10 microM) nor tetraethylammonium (1 mM) affected the
      relaxation induced by HA(60%). Incubation of the tissues with L-NAME
      significantly enhanced the maximal contraction induced by acetylcholine,
      indicating an inhibitory role for NO in the modulation of the contractile
      response of anococcygeus smooth muscle to acetylcholine. However, simultaneous
      addition of L-NAME and HA(60%) resulted in an effect similar to that observed
      with L-NAME alone, further confirming the observation that Pimpinella anisum acts
      by realizing NO. Additionally, HA(60%) did not alter CaCl(2)-induced contraction.
      Collectively, our results provide functional evidence that the effects elicited
      by the hidroalcoholic extract of Pimpinella anisum involve the participation of
      NO and subsequent activation of the NO-cGMP pathway. The relaxant action
      displayed by Pimpinella anisum justifies its use in the folk medicine as an
      antispasmodic agent.

PMID- 17027209
TI  - Using tibia fragments from South Africans of European descent to estimate maximum
      tibia length and stature.
AB  - Intact long limb bones have been used in the derivation of regression equations
      for stature assessment in different population groups. Since intact long bones
      are not always present for analyses in forensic cases, it has become necessary to
      derive regression equations for the estimation of stature from the fragments of
      these bones which are obtained in forensic and archaeological cases. Regression
      equations have been derived for stature estimation from fragments of the tibia.
      Since these equations are population specific, it was the aim of this study to
      derive similar equations for estimation of stature and maximum tibia length from
      measurements of different fragments of tibia of South Africans of European
      descent. Analyses were based on a sample of 50 male and 50 female complete
      skeletons of adult South Africans of European descent. Total skeletal height for
      the individual skeletons was measured using the Fully's (anatomical) method. Six
      variables were measured on the tibia which included the medial tibial condyle
      lengths and breadths, lateral tibial condyle lengths and breadths, proximal
      breadth and distal breadth. Univariate and multivariate regression equations were
      formulated for estimation of total skeletal height (and subsequent estimation of
      living stature) and maximum tibial length from measurements of the tibia. The
      standard errors of estimate for the equations were higher than those obtained for
      intact long bones which when present in forensic cases should be used for stature
      estimation. In the absence of intact long bones, the equations derived from the
      present study can provide a reliable estimate of skeletal height and living
      stature.

PMID- 17027211
TI  - Motor and reflex testing in GM1-gangliosidosis model mice.
AB  - A large number of genetic disease model mice have been produced by genetic
      engineering. However, phenotypic analysis is not sufficient, particularly for
      brain dysfunction in neurogenetic diseases. We tried to develop a new assessment
      system mainly for motor and reflex functions in G(M1)-gangliosidosis model mice.
      Two genetically engineered model mouse strains were used for this study: the beta
      galactosidase-deficient knockout mouse representing infantile G(M1)
      gangliosidosis (severe form), and transgenic mouse representing juvenile G(M1)
      gangliosidosis (mild form). We modified human child neurology techniques, and
      selected eleven tests for motor assessment and reflex testing. The test results
      were scored in four grades: 0 (normal), 1 (slightly abnormal), 2 (moderately
      abnormal), and 3 (severely abnormal). Both disease model mouse strains showed
      high scores even at the apparently pre-symptomatic stage of the disease,
      particularly with abnormal tail and hind limb postures. Individual and total test
      scores were well correlated with the progression of the disease. This method is
      simple, quick, and reproducible. The testing is sensitive enough to detect early
      neurological abnormalities, and will be useful for monitoring the natural
      clinical course and effect of therapeutic experiments in various neurogenetic
      disease model mice, such as chemical chaperone therapy for G(M1)-gangliosidosis
      model mice.

PMID- 17027212
TI  - [Observance of antiretroviral treatments: African specificities].
AB  - Since the Durban conference in 2000, the initiatives of access to antiretroviral
      therapy (ART) have expanded in sub-Saharan Africa. It is of high interest to
      monitor observance to HAART, in a context of increasing ART use, a rapid increase
      of patients under HAART, and the sociocultural specificities in Africa. In sub
      Saharan Africa the concept of disease without cure does not exist and a disease
      always has or is attributed an external cause. Optimizing observance is a key
      element for the success of implementation programs for which we recommend a light
      monitoring to follow-up patients and the use of first line and effective
      antiretroviral drugs, with a low genetic barrier (efavirenz, nevirapine). The
      consequences of non-adherence are extremely negative for a patient in Africa, for
      whom we have few assessment tools and a limited number of ART. Improvement of
      adherence requires the involvement of all health care actors including
      traditional healers.

PMID- 17027213
TI  - [Impact of antibiotic use and prescribing policy in a Tunisian intensive care
      unit].
AB  - OBJECTIVE: The aim of this study was to assess the efficacy of local antibiotic
      policy in a Tunisian ICU. The predefined primary efficacy objectives were the
      decrease of antibiotic consumption, reduction of inappropriate antibiotic (ATB)
      use and antimicrobial resistance. DESIGN: This prospective intervention study
      lasted from January 2002 to December 2004. In the first study period or the
      baseline phase (from January to December 2002) we focused on physician education
      for ATB prescription practice. The second period concerned intervention (control
      of all ATB use). RESULTS: The number of infection episodes significantly
      decreased from 2002 to 2004; 198 infection episodes in 2002 (1.63+/-1.15
      episodes/patient) versus 124 in 2003 (1.22+/-0.93) (P<0.0008) versus 121 in 2004
      (1.23+/-0.8) (P1<0.0008). The number of ATB/prescription also significantly
      decreased from 1.85+/-1.3 in 2002 to 1.5+/-0.9 in 2003 (P=0.02) and 1.5+/-1.4 in
      2004 (P1=0.05). Appropriateness of antibiotherapy improved during the
      intervention period: 65% in 2002 versus 86% in 2003 (P=0.0003) and 81% in 2004
      (P1=0.02). The length of antibiotherapy in survivors was considerably reduced:
      14.1+/-2.9 days in 2002 versus 11.9+/-1.2 days in 2003 (P<10(-5)) and 10.9+/-2.5
      days in 2004 (P1<10(-5)) with a significant reduction of antibiotherapy cost and
      length of stay (20.4+/-9 days in 2002 versus 18.3+/-6 days in 2003 and 16.9+/-8
      days in 2004; P=0.05; P1=0.02). There was a significant decrease of carbapenem
      resistant Enterobacteriaceae esbeta, Pseudomonas aeruginosa and Acinetobacter
      baumannii.

PMID- 17027214
TI  - [A case of severe community acquired pneumonia and non-respiratory illness
      induced by Influenza A].
AB  - BACKGROUND: Severe community acquired pneumonia is a common cause of acute
      respiratory failure. The influenza virus itself can cause a severe pneumonia and
      non-respiratory illness. CASE REPORT: A physician developed an acute respiratory
      failure associated with hemolytic anemia, acute renal failure, and myocarditis.
      Influenza A infection was diagnosed by screening for antibodies (complement
      fixation, ELISA Ig A). DISCUSSION: Fulminant influenza pneumonia is a rare
      clinical presentation of influenza infection and usually has a severe clinical
      course. Influenza infection is also associated with myositis, myocarditis, acute
      renal failure, encephalopathy, and hemolytic anemia. Rapid laboratary diagnosis
      can be made by PCR or immunofluorescence applied directly to respiratory
      specimens. Antiviral treatment did not prove its efficacy in fulminant Influenza.
      This case report is an opportunity to stress the importance of seroprophylaxis by
      parenteral vaccination in exposed occupations.

PMID- 17027215
TI  - [Rhinocerebral mucormycosis: A case report].
AB  - Mucormycosis is a rare and acute fungal infection which is frequently lethal,
      usually observed in non-controlled diabetic patients. The infection usually
      begins in the nose but it can invade the lung, the digestive tract, and the skin.
      Rhinocerebral mucormycosis accounts for 40 to 49% of mucormycosis cases. We
      report the case of a 53-year-old diabetic man, with chronic renal failure,
      presenting with rhinocerebral mucormycosis. Our patient was treated by an
      association of amphotericin B and surgical debridement. This observation provides
      on opportunity to recall clinical, histopathological, and therapeutic aspects of
      rhinocerebral mucormycosis.

PMID- 17027216
TI  - [Human babesiosis].
AB  - Babesia is one of the most ubiquitous and widespread blood parasite in the world
      based on numbers and distribution of species in animals. The clinical
      presentation may vary according to the incriminated species. In some states of
      the USA this kind of infection is endemic; the number of cases reported in Europe
      is inferior but more life-threatening. A better understanding of parasite
      specificities such as cycle and pathogenicity allowed to suggest treatment
      guidelines adapted to the different clinical and microbiological situations.

PMID- 17027217
TI  - [Legionnaire's disease complicated by acute renal failure due to rhabdomyolosis:
      a case report].
AB  - The infectious origin of non-traumatic rhabdomyolysis is rare (5% of cases). An
      elevated muscle enzyme level is often reported in the legionnaire's disease. We
      report the case of a 39-year-old male, with no previous medical history, admitted
      for renal failure (creatininemia=977 micromol/l) secondary to rhabdomyolysis and
      a twelve-day history of infectious syndrome with pneumonia in the left base.
      Legionella pneumophila was considered responsible for these symptoms because of a
      positive serology. The other microbial assessments were negative. After
      rehydration and three weeks of antibiotics, the outcome was favorable: the renal
      failure resolved completely and the muscle enzyme level returned to normal.

PMID- 17027218
TI  - [Role of antiviral drugs in containing pandemic influenza. Contribution of recent
      modelling exercises synthesis prepared by the InVS/Inserm "epidemiology" group -
      November 2005].
AB  - The growing threat of influenza pandemic has lead many countries to stockpile
      specific antiviral drugs, mainly oseltamivir, as it can be used both for
      prophylaxis and therapy. Several recently published studies, based on
      mathematical modelling, have assessed the impact of a large scale use of this
      drug to contain an emerging pandemic, slow its spread within a country or reduce
      its epidemiological impact. They conclude that ring antiviral prophylaxis around
      the first cases, combined with social distancing measures, may halt a nascent
      pandemic, if the human-to-human transmissibility of the virus is limited and the
      control measures implemented promptly and with a high coverage. In case of
      failure, these same strategies could delay the spread of the virus within a
      country. The use of influenza antiviral drugs would reduce the burden of disease
      and even the clinical attack rate, under the assumption of a shorter infectious
      period for treated patients. These studies are in favour of stockpiling influenza
      antiviral drugs, at least to cover the curative needs and, even better, to
      contribute to the global effort to contain an emergent pandemic and to allow an
      intervention around the first chains of indigenous transmission in a country,
      thus slowing the virus spread. These results are based on the hypothesis of the
      effectiveness of oseltamivir on the pandemic virus and confirm the critical
      importance of a sensitive and reactive surveillance.

PMID- 17027219
TI  - [Optimal vancomycin serum level in Staphylococcus aureus infections?].
AB  - Vancomycin is the cornerstone of therapy against methicillin-resistant
      Staphylococus aureus in both community and nosocomial-acquired infections.
      Because vancomycin is a concentration-independent or time-dependant antibiotic,
      most clinicians have abandoned the routine practice of determining peak serum
      concentrations to rely solely on monitoring serum concentrations. The so-called
      therapeutic range most often quoted for vancomycin was assessed for through serum
      concentrations of 5-10 mg/l. But prolonged exposure to serum concentration close
      to the MIC is associated with the emergence of resistance. More recent guidelines
      recommended vancomycin in concentrations of 15-20 mg/l for the treatment of
      severe Staphylococcus infections or in situations where vancomycin penetration is
      poor. However, because of the great variability of vancomycin MIC(S) (0,12-4
      mg/l) of susceptible Staphylococcus strains, guidelines should recommend through
      serum concentrations of 5-10 times the MIC.

PMID- 17027220
TI  - Alkalibacillus halophilus sp. nov., a new halophilic species isolated from
      hypersaline soil in Xin-Jiang province, China.
AB  - A halophilic, Gram-positive, spore-forming motile Bacillus-like strain YIM
      012(T), was isolated from one of the hypersaline soil samples collected in Xin
      jiang province, China. Its optimum growth occurred at 10-20% of NaCl
      concentration (w/v), pH 7.0-8.0. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain YIM 012(T) is a member of the genus of
      Alkalibacillus, which is well supported by its chemotaxonomic and molecular
      characteristics. Based on its phenotypic evidence and genotypic data,
      Alkalibacillus halophilus sp. nov. was proposed and strain YIM 012(T) (=DSM
      17369(T)=KCTC 3990(T)) was assigned as the type strain of the novel species.

PMID- 17027221
TI  - The extent and breadth of benefits from participating in chronic disease self
      management courses: a national patient-reported outcomes survey.
AB  - OBJECTIVE: To quantify the benefits that people receive from participating in
      self-management courses and identify subgroups that benefit most. METHODS: People
      with a wide range of chronic conditions attending self-management courses (N =
      1341 individuals) were administered the Health Education Impact Questionnaire
      (heiQ). Baseline and follow-up data were collected resulting in 842 complete
      responses. Outcomes were categorized as substantial improvement (effect size, ES
      > or = 0.5), minimal/no change (ES -0.49 to 0.49) and substantial decline (ES <
      or = -0.5). RESULTS: On average, one third of participants reported substantial
      benefits at the end of a course and this ranged from 49% in the heiQ subscale
      Skill and technique acquisition to 27% in the heiQ subscale Health service
      navigation. Stratification by gender, age and education showed that younger
      participants were more likely to benefit, particularly young women. No further
      subgroup differences were observed. CONCLUSION: While the well-being of people
      with chronic diseases tends to decline, about one third of participants from a
      wide range of backgrounds show substantial improvements in a range of skills that
      enable them to self-manage. PRACTICE IMPLICATIONS: These data support the
      application of self-management courses indicating that they are a useful adjunct
      to usual care for a modest proportion of attendees.

PMID- 17027223
TI  - Exhaustive genotyping of the interferon alpha receptor 1 (IFNAR1) gene and
      association of an IFNAR1 protein variant with AIDS progression or susceptibility
      to HIV-1 infection in a French AIDS cohort.
AB  - We have undertaken a systematic genomic approach in order to explore the role of
      the interferon alpha (IFN-alpha) pathway in AIDS disease development. As it is
      very difficult to genotype the IFN-alpha gene itself since it has many pseudo
      genes, we have focused our interest on the genetic polymorphisms of the IFN-alpha
      receptor 1 (IFNAR1). We genotyped the Genetics of Resistance to Immunodeficiency
      Virus (GRIV) cohort composed of patients with extreme profiles of progression to
      AIDS, slow progressors (SP) and rapid progressors (RP), as well as seronegative
      controls (CTR). We identified 19 single nucleotide polymorphisms (SNPs) with a
      minor allele frequency (MAF) greater than 1% among which two were newly
      characterized by our study. We found putative associations with AIDS disease
      development for four SNP alleles and for three haplotypes. The most interesting
      signals were found for two SNPs in linkage disequilibrium, the SNP IFNAR1_18339
      corresponding to a Val168Leu mutation in the extracellular domain of the protein
      and the intronic SNP, IFNAR1_30127. The intronic SNP IFNAR1_30127 yielded a
      strong signal both when comparing SP with CTR (P=0.002) and RP with CTR (P=0.005)
      while IFNAR1_18339 yielded a smaller signal because less patients were analyzed;
      these SNPs could thus be involved in AIDS progression or in susceptibility to
      human immunodeficiency virus 1 (HIV-1) infection. Interestingly, two independent
      studies have previously pointed out the SNP IFNAR1_18339 in susceptibility to
      multiple sclerosis and to malaria. This is the first work investigating the
      polymorphisms of the IFNAR1 gene in AIDS. Our results which point out a possible
      role for the IFN-alpha pathway in susceptibility to HIV-1 infection or
      progression to AIDS need a necessary confirmation by genomic studies in other
      AIDS cohorts.

PMID- 17027222
TI  - [Paracervical block in obstetrics].
AB  - OBJECTIVE: To review the most recent and relevant issues concerning paracervical
      block in obstetrics since 1975 when Jagerhorn described the superficial technique
      that has become a standard. DATA SOURCES: Extraction from Pubmed database of
      articles issued from 1975 to 2005. DATA SELECTION: The collected articles were
      selected on the basis of the use of the superficial injection method. The more
      recent data were selected. The keywords were: paracervical, labour, childbirth,
      and neonate. DATA SYNTHESIS: Paracervical block (PCB) is routinely used over the
      world despite the risk of foetal bradycardia. Bradycardia occurring immediately
      after the performance of block is short lasting. The reports of few cases of
      foetal or neonatal deaths have caused many physicians to question its safety. The
      incidence of bradycardia has dramatically decreased (less than 10%) due to the
      Jagerhorn superficial injection method. In case of healthy neonate the occurrence
      of bradycardia is harmless but its mechanism is still imprecise. The intensity an
      duration of analgesia is poor in comparison with epidural anaesthesia. PCB is a
      viable alternative to epidural in selected cases.

PMID- 17027224
TI  - Characterization of multipotent cells from human adult hair follicles.
AB  - Recent works demonstrated the presence of a multipotent epithelial cell
      population in the bulge region of adult human hair follicles. These cells can be
      cultured in vitro, thus leading to the preparation of dermal-epidermal
      substitutes which are applicable in the treatment of burns and ulcers. We
      evaluated the main marker expression in cells obtained from stripped human hair
      follicles. A pool of hair follicles were incubated at 37 degrees C and 5% CO(2)
      in a growth medium. The cells were then labelled with antibodies (anti-CD34, anti
      CD38, anti-CD45, anti-CD90, anti-CD133, anti-CD146) and analysed by cytometry. We
      also used hair follicles for immunohistochemical studies, employing antibodies
      such as CD34, Actin Smooth Muscle, Filaggrin, Desmin, Vimentin, Glial Fibrillary
      Acidic Protein, Ki-67, PanCytokeratin, CK15, CK19. The cytometry results revealed
      that a part of bulge cells were CD34+ (1-2%). CD34+ population comprises both
      large, CD45-, CD133-, CD146- cells and small, CD45+, CD133+, CD146+ cells. Thus,
      a part of CD34+ cells present a mature endothelial marker (CD146). An expression
      of the proliferation marker Ki-67 and the stem cell marker CD34 is present in the
      follicle bulge region. In conclusion, we observed that the stripped hair follicle
      has the same multipotent cell population as adult and fetal scalp hair follicles.

PMID- 17027226
TI  - Cognitive conflict without explicit conflict monitoring in a dynamical agent.
AB  - We examine mechanisms for resolving cognitive conflict in an embodied, situated,
      and dynamic agent, developed through an evolutionary learning process. The agent
      was required to solve problems of response conflict in a dual-target "catching"
      task, focusing response on one of the targets while ignoring the other. Conflict
      in the agent was revealed at the behavioral level in terms of increased latencies
      to the second target. This behavioral interference was correlated to peak
      violations of the network's stable state equation. At the level of the agent's
      neural network, peak violations were also correlated to periods of disagreement
      in source inputs to the agent's motor effectors. Despite observing conflict at
      these numerous levels, we did not find any explicit conflict monitoring
      mechanisms within the agent. We instead found evidence of a distributed conflict
      management system, characterized by competitive sources within the network. In
      contrast to the conflict monitoring hypothesis [Botvinick, M. M., Braver, T. S.,
      Barch, D. M., Carter, C. S., & Cohen, J. D. (2001). Conflict monitoring and
      cognitive control. Psychological Review, 108(3), 624-652], this agent
      demonstrates that resolution of cognitive conflict does not require explicit
      conflict monitoring. We consider the implications of our results for the conflict
      monitoring hypothesis.

PMID- 17027225
TI  - Selective attention through phase relationship of excitatory and inhibitory input
      synchrony in a model cortical neuron.
AB  - Neurons in area V2 and V4 exhibit stimulus specific tuning to single stimuli, and
      respond at intermediate firing rates when presented with two differentially
      preferred stimuli ('pair response'). Selective attention to one of the two
      stimuli causes the neuron's firing rate to shift from the intermediate pair
      response towards the response to the attended stimulus as if it were presented
      alone. Attention to single stimuli reduces the response threshold of the neuron
      and increases spike synchronization at gamma frequencies. The intrinsic and
      network mechanisms underlying these phenomena were investigated in a multi
      compartmental biophysical model of a reconstructed cat V4 neuron. Differential
      stimulus preference was generated through a greater ratio of excitatory to
      inhibitory synapses projecting from one of two input V2 populations. Feedforward
      inhibition and synaptic depression dynamics were critical to generating the
      intermediate pair response. Neuronal gain effects were simulated using gamma
      frequency range correlations in the feedforward excitatory and inhibitory inputs
      to the V4 neuron. For single preferred stimulus presentations, correlations
      within the inhibitory population out of phase with correlations within the
      excitatory input significantly reduced the response threshold of the V4 neuron.
      The pair response to simultaneously active preferred and non-preferred V2
      populations could also undergo an increase or decrease in gain via the same
      mechanism, where correlations in feedforward inhibition are out of phase with
      gamma band correlations within the excitatory input corresponding to the attended
      stimulus. The results of this model predict that top-down attention may bias the
      V4 neuron's response using an inhibitory correlation phase shift mechanism.

PMID- 17027227
TI  - The N-terminal SH2 domain of the tyrosine phosphatase, SHP-2, is essential for
      Jak2-dependent signaling via the angiotensin II type AT1 receptor.
AB  - Previous work has suggested that the protein tyrosine phosphatase, SHP-2, may act
      to facilitate angiotensin II (Ang II)-mediated, Jak2-dependent signaling.
      However, the mechanisms by which this occurs are not known. Here, Ang II
      mediated, Jak2-dependent signaling was analyzed in a fibroblast cell line lacking
      the N-terminal, SH2 domain of SHP-2 (SHP-2(Delta46-110)). While the SHP-2(Delta46
      110) cells were capable of activating Jak2 tyrosine kinase, they were unable to
      facilitate AT1 receptor/Jak2 co-association, STAT activation and subsequent Ang
      II-mediated gene transcription when compared to wild type control cells. These
      data therefore suggested that the N-terminal SH2 domain of SHP-2 was acting to
      recruit Jak2 to the AT1 receptor signaling complex. We found that the N-terminal
      SH2 domain of SHP-2 binds Jak2 predominantly, but not exclusively at tyrosine
      201. Mass spectrometry analysis confirmed that this tyrosine residue is in fact
      phosphorylated. When this tyrosine was converted to phenylalanine, the ability of
      Jak2 to activate subsequent downstream signaling events was reduced. In summary,
      we have identified a novel site of Jak2 tyrosine autophosphorylation; namely,
      tyrosine 201. Our data suggest that the N-terminal SH2 domain of SHP-2 binds this
      amino acid residue. The functional consequence of this interaction is to recruit
      Jak2 to the AT1 receptor signaling complex and in turn promote downstream Jak2
      dependent signaling.

PMID- 17027228
TI  - Wnt-3a utilizes a novel low dose and rapid pathway that does not require casein
      kinase 1-mediated phosphorylation of Dvl to activate beta-catenin.
AB  - The current view of canonical Wnt signalling is that following Wnt binding to its
      receptors (Frizzled-Lrp5/6), dishevelled (Dvl) becomes hyperphosphorylated, and
      the signal is transduced to the APC-GSK3beta-axin-beta-catenin multiprotein
      complex, which subsequently dissociates. As a result beta-catenin is not
      phosphorylated, escapes proteosomal degradation and activates its target genes
      after translocation to the nucleus. Here, we analyzed the importance of the Wnt
      3a-induced phosphorylation and shift in electrophoretic migration of Dvl (PS-Dvl)
      for the activation of beta-catenin. Analysis of Wnt-3a time- and dose-responses
      in a dopaminergic cell line showed that beta-catenin is activated rapidly (within
      minutes) and at a low dose of Wnt-3a (1 ng/ml). Surprisingly, PS-Dvl appeared
      only after 30 min and at greater doses (> or =20 ng/ml) of Wnt-3a. Moreover, we
      found that a casein kinase 1 inhibitor (D4476) or siRNA for casein kinase 1
      delta/epsilon (CK1delta/epsilon) blocked the Wnt-3a-induced PS-Dvl.
      Interestingly, CK1 inhibition or siRNA for CK1delta/epsilon did not ablate the
      activation of beta-catenin by Wnt-3a, indicating that there is a PS-Dvl
      independent path to activate beta-catenin. The increase in beta-catenin
      activation by Wnt-3a (PS-Dvl-dependent or -independent) were blocked by Dickkopf1
      (Dkk1), suggesting that the effect of Wnt-3a is in both cases mediated by Lrp5/6
      receptors. Thus, our results show that Wnt-3a rapidly induce a partial activation
      of beta-catenin in the absence of PS-Dvl at low doses, while at high doses induce
      a full activation of beta-catenin in a PS-Dvl-dependent manner.

PMID- 17027230
TI  - Longitudinal study of body composition changes associated with weight change and
      physical activity.
AB  - OBJECTIVE: Weight changes result in fat-free mass (FFM) and body fat (BF)
      changes. This study determined FFM and BF changes after weight gain or loss and
      whether these changes differ by gender, physical activity, and age. METHODS:
      Healthy volunteers, recruited between 1991 and 2003, were followed for 1 y (n =
      400) or 3 y (n = 305). Active subjects performed >3 h of physical activity of >
      or =4.0 metabolic equivalents/wk, sedentary subjects performed <3 h/wk. Body
      weight and body composition by bioelectrical impedance analysis were determined
      at year 0, 1, or 3. RESULTS: At years 1 and 3, FFM and BF decreased with weight
      loss and increased with weight gain. BF was more sensitive (P < 0.03) to weight
      change than FFM. Compared to weight-stable individuals at year 1, weight gains of
      1.0-1.9, 2.0-2.9, and > or =3.0 kg changed FFM by -0.04 (P = 0.90), +0.48 (P =
      0.15), and +1.39 kg and BF by +1.35, +1.87, and +3.09 kg, respectively (all P <
      0.001). Comparable FFM and BF decreases were observed for weight losses (FFM 
      0.28 kg, P = 0.38; -0.75 kg, P = 0.04; -1.51 kg, P < 0.001; BF -1.01 kg, P <
      0.01; -1.55 kg, P = 0.01; -3.13 kg, P < 0.001). These relations were similar
      across gender and age strata. At year 1, active individuals were less likely to
      gain BF with weight gain and more likely to lose BF with weight loss than were
      sedentary individuals, except for weight losses >3 kg. At year 3, the association
      between body weight and FFM and BF change was similar between active and
      sedentary individuals. CONCLUSION: Greater weight changes (>3 kg) are necessary
      for weight change to have a significant effect on FFM than to have an effect on
      BF.

PMID- 17027231
TI  - Allicin, a major component of garlic, inhibits apoptosis of macrophage in a
      depleted nutritional state.
AB  - OBJECTIVE: Allicin is believed to be the main component responsible for the
      biological activity of garlic. The regulation of cell death might have
      therapeutic potential in many diseases, and previous studies have demonstrated
      that allicin stimulates the functional activity of macrophages. Therefore, this
      study examined the effects of allicin on the apoptosis of macrophages induced by
      serum- and amino acid-free culture. METHODS: The apoptosis of peritoneal
      macrophages was examined after pretreating them with allicin and incubating them
      in a depleted nutritional state. The rate of apoptosis was determined using
      propidium iodide staining analysis using flow cytometry, DNA fragmentation, and a
      caspase-3 assay. Western blot analysis was used to examine the changes in the pro
      or antiapoptotic protein expression levels. RESULTS: DNA fragmentation and
      propidium iodide staining analyses revealed that allicin decreased the
      malnutrition-induced apoptosis of macrophages. The level of Bax expression, the
      amount of cytochrome-c released from the mitochondria, and the caspase-3 activity
      were also lower in the allicin-treated macrophages than in the untreated
      macrophages in a depleted nutritional state. Moreover, the MEK (mitogen-activated
      protein kinase/extracellular signal-regulated kinase-kinase) inhibitor suppressed
      the allicin-induced inhibition of apoptosis in a depleted nutritional state and
      allicin increased the level of ERK1/2 phosphorylation. CONCLUSION: Allicin
      inhibits the apoptosis of macrophages in a depleted nutritional state through the
      MEK/extracellular signal-regulated kinase pathway.

PMID- 17027229
TI  - Low-carbohydrate and high-fat intake among adult patients with poorly controlled
      type 2 diabetes mellitus.
AB  - OBJECTIVE: This study examined baseline dietary intake, body weight, and
      physiologic status in patients enrolled in a dietary intervention for type 2
      diabetes mellitus (T2DM). METHODS: Dietary, physiologic, and demographic
      information were collected at baseline from 40 adult patients with poorly
      controlled T2DM (glycosylated hemoglobin >7%) who participated in a clinical
      trial at an academic medical center in Worcester, Massachusetts, USA. RESULTS:
      The average age at enrollment was 53.5 y (SD 8.4), average body mass index was
      35.48 kg/m(2) (SD 7.0), and glycosylated hemoglobin was 8.3% (SD 1.2).
      Participants were predominantly white, married, and employed full time. Forty
      eight percent were men. Seventy-eight percent had hyperlipidemia, and 68% had
      hypertension. Reported baseline daily average energy intake was 1778 kcal (SD
      814), daily carbohydrate was 159 g (SD 71.5), and dietary fiber was 11.4 g (SD
      5.2). The dietary composition was 35% carbohydrate, 45% fat (15% saturated fat),
      and 20% protein. The American Diabetes Association (ADA) guidelines recommends 45
      65% of energy from carbohydrate, 20-35% from fat (<7% saturated), and 20% from
      protein. CONCLUSION: These patients reported a low-carbohydrate, low-fiber, high
      fat (especially saturated) diet, although they stated they are not following any
      of the popular low-carbohydrate diets. Patients with T2DM may find the current
      trend toward reducing weight through low-carbohydrate diets attractive for
      control of blood glucose, despite ADA recommendations. This dietary pattern may
      represent a popular trend that extends beyond our particular study and, if so,
      has serious cardiovascular implications in this vulnerable population of T2DM
      patients.

PMID- 17027232
TI  - Effect of fish oil pretreatment on isoproterenol-induced changes in myocardial
      membrane phospholipids.
AB  - OBJECTIVE: In the present study, the protective effect of fish oil treatment on
      the fatty acid composition in isoproterenol (IPH)-induced myocardial infarction
      was studied in male albino Wistar rats. METHODS: Rats were injected for 2
      consecutive days with IPH (60 mg/kg body weight) at 24-h intervals to induce
      myocardial infarction. Fish oil was administered orally at a dose of 0.05 mL/d
      for 45 d, after which serum and heart tissue were assayed for lipid profile,
      lipoprotein changes, and myocardial membrane phospholipid fatty acid composition.
      RESULTS: Biochemical assessment of myocardial infarction was done by measuring
      the activities of creatinine kinase and lactate dehydrogenase, which were
      significantly elevated in the rats administered with IPH. Further, the
      administration of IPH modified the fatty acid composition and analysis of fatty
      acids showed there was an increase in the omega-3/omega-6 ratio in phospholipid
      pool. In addition, increased levels of total cholesterol, free cholesterol, ester
      cholesterol, phospholipids, triacylglycerols and free fatty acid was observed in
      serum and heart tissue of IPH-induced rats. The fish oil treatment for a period
      of 45 d decreased the levels of cardiac markers (creatinine kinase and lactate
      dehydrogenase) and reversed the biochemical lesions induced by IPH. CONCLUSION:
      Our study suggests that fish oil treatment has a hypolipidemic effect and has
      potential use in the treatment of myocardial infarction.

PMID- 17027233
TI  - Konjac acts as a natural laxative by increasing stool bulk and improving colonic
      ecology in healthy adults.
AB  - OBJECTIVE: Konjac glucomannan (KGM) has been shown to relieve constipation, which
      could be associated with increased stool bulk and improved colonic ecology.
      METHODS: This placebo-controlled study consisted of a 21-d placebo period, a 7-d
      adaptation period when volunteers consumed KGM progressively, and a 21-d KGM
      supplemented period (1.5 g/meal, 4.5 g/d). Eight healthy adults consumed 7-d
      cycle menus of typical low-fiber Chinese food throughout the study. The
      gastrointestinal response was monitored daily. Stools were fully collected on
      days 15 to 21 of placebo and KGM periods to determine the fecal mass, components,
      microflora, and short-chain fatty acid contents. RESULTS: The KGM supplement
      significantly increased the mean defecation frequency (number/day), wet stool
      weight, and dry stool weight (g/d) by approximately 27.0% (P < 0.05), 30.2% (P <
      0.05), and 21.7% (P < 0.05), respectively. The dry fecal mass increased mainly in
      the plant and soluble material, whereas bacterial mass tended to increase from
      12.9 +/- 1.6 to 13.6 +/- 2.7 g/d (P > 0.05). However, KGM significantly promoted
      the fecal concentrations (log counts/g wet feces) of lactobacilli (P < 0.05) and
      total bacteria (P < 0.05), and promoted the daily output (log counts per day) of
      bifidobacteria (P < 0.05), lactobacilli (P < 0.05), and total bacteria (P < 0.05)
      as evaluated by the fluorescence in situ hybridization method. KGM supplement
      also promoted colonic fermentation as shown in the decreased fecal pH (P < 0.05)
      and increased fecal short-chain fatty acid concentrations (P < 0.05). CONCLUSION:
      Supplementation of KGM into a low-fiber diet promoted the defecation frequency in
      healthy adults, possibly by increasing the stool bulk, thus promoting the growth
      of lactic acid bacteria and colonic fermentation.

PMID- 17027234
TI  - Resonance frequency measurements of implant stability in the dog mandible:
      experimental comparison with histomorphometric data.
AB  - The aim of the present study was to test the hypothesis that measurements of
      implant stability using resonance frequency analysis (RFA) correlate with
      histomorphometric data of bone anchorage. Ten adult female foxhounds received a
      total of 80 implants in their mandibles 3 months after removal of all premolar
      teeth. At the time of implant placement, torque required for bone tapping was
      registered as a measure of bone density and immediately after placement implant
      stability was assessed using RFA. RFA measurements were repeated at the time of
      implant retrieval after 1 month (5 dogs) and 3 months (5 dogs). Peri-implant bone
      regeneration was assessed histomorphometrically by measuring bone-implant contact
      (BIC) and the volume density of the newly formed peri-implant bone (BVD). RFA
      values at the time of implant placement did not correlate with the torque
      required to tap the bone for implant placement. After 1 and 3 months, RFA values
      were significantly increased compared with baseline values. BIC and BVD, however,
      had increased significantly during this interval. There was no correlation
      between bone-implant contact and RFA values nor between peri-implant bone density
      and RFA values. Thus, the hypothesis could not be verified. It is concluded that
      the validity of the individual measurement of implant stability using RFA should
      be considered with caution.

PMID- 17027235
TI  - Osseointegration of oxidized and turned implants in circumferential bone defects
      with and without adjunctive therapies: an experimental study on BMP-2 and
      autogenous bone graft in the dog mandible.
AB  - The aim of the study was to compare the integration and implant stability of
      turned and oxidized titanium implants when placed in experimental bone defects
      with autogenous bone graft, BMP-2 or without adjunctive therapy. Four defects
      were prepared on each side of the mandible of 12 mongrel dogs five months after
      tooth extractions. Implants with turned and oxidized surfaces were placed in the
      defects. The circumferential gaps were filled with either autogenous bone grafts,
      a BMP-allogeneic dog mixture in a thermoplastic carrier, carrier alone or left
      without any treatment (control). There were no statistically significant
      differences between control and treated sites, neither for turned nor for
      oxidized implants with regard to histomorphometric measurements in ground
      sections and to implant stability as measured with resonance frequency analysis
      (RFA) after 4 and 12 weeks of healing. However, oxidized implants showed a
      significantly higher stability after 4 weeks and a tendency (p < 0.1) of that
      after 12 weeks. Histomorphometry showed more bone contacts for oxidized than for
      turned implants. It is concluded that oxidized implants gain stability more
      rapidly and integrate with more bone contacts than implants with a turned surface
      when placed in bone defects.

PMID- 17027236
TI  - MRI abnormalities of the hippocampus and cavum septi pellucidi in females with
      schizotypal personality disorder.
AB  - OBJECTIVE: This study examined MRI hippocampal volume and cavum septi pellucidi
      (CSP) in female subjects with schizotypal personality disorder (SPD) and
      comparison subjects. METHOD: MRI was performed on 20 SPD and 29 comparison
      subjects with delineation of left and right hippocampi. Number of slices
      containing the CSP was counted. Subjects were given a working memory task, the
      Delayed Alternation task and other measures of working memory including the
      Wechsler Memory Test-Revised and the California Verbal Learning Test. Clinical
      measures were derived from the SCID-II. RESULTS: SPD females evinced bilaterally
      smaller hippocampal volumes compared with non-psychiatric female subjects (15.1%
      on left, 15.7% on right). Additionally, SPD subjects showed statistically
      significantly more slices containing CSP, and a trend level difference when large
      CSP was defined as four or more slices (20% vs. 6.9%). SPD subjects demonstrated
      more errors, more perseverations, and a trend toward more failure to maintain set
      on the Delayed Alternating task, which were associated with smaller left
      hippocampal volumes. There was no difference between groups in logical memory,
      verbal learning or semantic clustering nor a significant correlation between
      these measures and hippocampal volumes. Clinically, in SPD subjects, right
      hippocampal volumes correlated negatively with odd appearance/behavior and
      positively with suspiciousness/paranoia, and odd speech was positively correlated
      with the number of slices containing a CSP in exploratory analyses. CONCLUSIONS:
      Female SPD subjects showed bilaterally smaller hippocampal volumes and larger CSP
      than comparison subjects, similar to what has been shown in schizophrenia.
      Moreover, these abnormalities have clinically significant associations which may
      help to explain some of the manifestations of the disorder.

PMID- 17027237
TI  - CTX-M-1- and CTX-M-15-type beta-lactamases in clinical Escherichia coli isolates
      recovered from food-producing animals in France.
AB  - Clinical Escherichia coli strains with resistance or variable susceptibility to
      third-generation cephalosporins were detected in cattle, swine and poultry in
      France. These strains were shown to produce extended-spectrum beta-lactamases
      (ESBLs), with CTX-M-1- and CTX-M-15-type beta-lactamases being responsible for
      this phenotype. The bla(CTX-M-1) gene was encountered most commonly and was
      characterised in seven E. coli strains isolated from cattle, swine and poultry,
      whereas bla(CTX-M-15) was identified in one E. coli isolated from cattle. These
      genes were located on a conjugative plasmid and were linked to the insertion
      sequence ISEcp1, which could have contributed to dissemination of the resistance
      gene. No epidemiological link between the strains was determined by pulsed-field
      gel electrophoresis, although two plasmids were identical in two strains isolated
      from swine and in two strains isolated from cattle and poultry. Thus, this study
      describes the emergence of ESBLs in animals in France, with a probable similar
      prevalence rate to that observed in humans. This is a major concern because of
      the possibility of transfer of these genes between animal species as well as to
      humans, leading to treatment failures in veterinary and human medicine.

PMID- 17027238
TI  - Fate map of the distal portion of Drosophila proboscis as inferred from the
      expression and mutations of basic patterning genes.
AB  - The late-third-instar labial disc is comprised of two disc-proper cell layers,
      one representing mainly the ventral half of the anterior compartment (L-layer)
      and the other, the dorsal half of the anterior compartment and most, if not all,
      of the posterior compartment (M-layer). In the L-layer, Distal-less represses
      homothorax whereas no Distal-less-dependent homothorax repression occurs in the M
      layer where Distal-less is coexpressed with homothorax. In wild-type labial
      discs, clawless, one of the two homeobox genes expressed in distal cells
      receiving maximum (Decapentaplegic+Wingless) signaling activity in leg and
      antennal discs, is specifically repressed by proboscipedia. A fate map, inferred
      from data on basic patterning gene expression in larval and pupal stages and
      mutant phenotypes, indicates the inner surface of the labial palpus, which
      includes the pseudotracheal region, to be a derivative of the distal portion of
      the M-layer expressing wingless, patched, Distal-less and homothorax. The outer
      surface of the labial palpus with more than 30 taste bristles derives from an L
      layer area consisting of dorsal portions of the anterior and posterior
      compartments, each expressing Distal-less. Our analysis also indicates that, in
      adults and pupae, the anterior-posterior boundary, dividing roughly equally the
      outer surface of the distiproboscis, runs along the outer circumference of the
      inner surface of distiproboscis.

PMID- 17027239
TI  - Dlx5- and Dlx6-mediated chondrogenesis: Differential domain requirements for a
      conserved function.
AB  - During endochondral ossification in the vertebrate limb, multipotent mesenchymal
      cells first differentiate into chondroblasts (chondrogenesis) that further
      differentiate (via chondrocyte hypertrophy) to a terminal cellular phenotype.
      Dlx5 and Dlx6 are functionally redundant regulators of chondrocyte hypertrophy.
      We now show that Dlx5 and Dlx6 also regulate the earlier step of chondrogenesis
      in the limb. Limb bud mesenchymal cells from Dlx5/6(-/-) embryos show reduced
      chondrogenesis compared to wild-type littermates, and expression of either Dlx5
      or Dlx6 stimulated differentiation of limb bud mesenchymal cells to
      chondroblasts. The functional overlap between Dlx5 and Dlx6 occurs despite the
      fact that the amino- and carboxyl-terminal domains of the encoded proteins are
      dissimilar. In order to reconcile the disparity between the divergent structures
      of Dlx5 and Dlx6 with their overlapping biological functions, we investigated the
      domain requirements and transcriptional activities associated with Dlx5- and Dlx6
      mediated chondrogenesis. We find distinct domain requirements for the
      chondrogenic function of these related homeoproteins, indicating divergent
      molecular mechanisms of action.

PMID- 17027240
TI  - [Maffucci syndrome: an historical case].
AB  - We report a case of Maffucci syndrome in a 24-year-old patient, diagnosed thanks
      to the data of the clinical examination, the imagery and the histology. The
      clinical, radiological and evolutionary aspects are discussed, as well as the
      various therapeutic means.

PMID- 17027241
TI  - Extending temporal databases to deal with telic/atelic medical data.
AB  - OBJECTIVE: In this paper, we aim at defining a general-purpose data model and
      query language coping with both "telic" and "atelic" medical data. BACKGROUND: In
      the area of Medical Informatics, there is an increasing realization that temporal
      information plays a crucial role, so that suitable database models and query
      languages are needed to store and support it. However, despite the wide range of
      approaches in the area, in this paper we show that a relevant class of medical
      data cannot be properly dealt with. METHODOLOGY: We first show that data models
      based on the "point-based" semantics, which is (implicitly or explicitly) assumed
      by the totality of temporal database approaches, have several limitations when
      dealing with "telic" data. We then propose a new model (based on the "interval
      based" semantics) to cope with such data, and extend the query language
      accordingly. RESULTS: We propose a new three-sorted model and a query language to
      properly deal with both "telic" and "atelic" medical data (as well as non
      temporal data). Our query language is flexible, since it allows one to switch
      from "atelic" to "telic" data, and vice versa. CONCLUSION: In this paper, we
      demonstrate the feasibility of a database approach copying with both telic and
      atelic data as needed in several (medical) applications.

PMID- 17027242
TI  - Circulating homocysteine levels in patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND AIM: Previous studies have shown conflicting results regarding
      circulating homocysteine levels in patients with type 2 diabetes. METHODS AND
      RESULTS: This observational study included 2121 patients with angiographically
      proven coronary artery disease (507 patients with type 2 diabetes and 1614
      patients without diabetes). Circulating homocysteine levels,
      methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal
      function, presence of coronary artery disease (CAD) diagnosed by coronary
      angiography, and circulating folate and vitamin B12 status were assessed. Plasma
      homocysteine levels [median (25th; 75th percentile)] were significantly higher in
      patients with diabetes than in those without [12.4 micromol/L (9.9 micromol/L;
      15.9 micromol/L) versus 11.7 micromol/L (9.6 micromol/L; 14.5 micromol/L),
      P=0.011]. Diabetes affected homocysteine levels only in patients with a
      glomerular filtration rate <90 mL/min [13.0 micromol/L (10.5 micromol/L; 16.7
      micromol/L) in patients with diabetes versus 12.2 micromol/L (10.1 micromol/L;
      15.2 micromol/L) in patients without diabetes, P=0.006] but not in those with a
      glomerular filtration rate > or = 90 mL/min [10.1 micromol/L (8.1 micromol/L;
      12.4 micromol/L) versus 10.2 micromol/L (8.8 micromol/L; 12.3 micromol/L),
      P=0.267]. Multivariable analysis did not show an independent association between
      diabetes and homocysteine level (P=0.342). CONCLUSION: Circulating homocysteine
      levels are increased in patients with type 2 diabetes compared with non-diabetic
      patients due to a more diabetes-associated adverse risk profile rather than to
      diabetes itself.

PMID- 17027243
TI  - Fate of micelles and quantum dots in cells.
AB  - Micelles and quantum dots have been used as experimental drug delivery systems
      and imaging tools both in vitro and in vivo. Investigations of their fate at the
      subcellular level require different surface-core modifications. Among the most
      common modifications are those with fluorescent probes, dense-core metals or
      radionucleids. Cellular fate of several fluorescent probes incorporated into
      poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal
      microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles
      were developed to explore micelle fate by electron microscopy. More recently, we
      have examined quantum dots (QDs) as the next-generation-labels for cells and
      nanoparticulate drug carriers amenable both to confocal and electron microscopic
      analyses. Effects of QDs at the cellular and subcellular levels and their
      integrity were studied. Results from different studies suggest that size, charge
      and surface manipulations of QDs may play a role in their subcellular
      distribution. Examples of pharmacological agents incorporated into block
      copolymer micelles, administered or attached to QD surfaces show how the final
      biological outcome (e.g. cell death, proliferation or differentiation) depends on
      physical properties of these nanoparticles.

PMID- 17027244
TI  - Effect of surfactant on dissolution of spherical particles in micellar systems.
AB  - The influence of micelle-drug solubilization on the dissolution rate of
      monodisperse particles of benzocaine has been investigated. A model describing
      and predicting the initial dissolution rates of spherical particles was derived
      starting from the boundary layer theory. The dissolution rate of benzocaine
      spherical particles was determined in water and in solutions of sodium lauryl
      sulfate (SLS) under static conditions. The derived model was applied to the
      experimental data. The diffusion coefficients and the aqueous diffusion layer
      values were estimated from the experimental results and the aforementioned model.
      The diffusion coefficients and the boundary layer thickness values were also
      obtained experimentally from the rotating disk method and were used to predict
      the initial dissolution rates. Excellent correlations were obtained between the
      experimental and the calculated values at low micellar concentrations. However,
      obvious deviation was observed at high micellar concentrations. The results
      obtained from this study suggest that it is possible to predict the initial
      dissolution rates of monodisperse particles in micellar systems.

PMID- 17027245
TI  - Stable high surface area lactate dehydrogenase particles produced by spray
      freezing into liquid nitrogen.
AB  - Enzyme activities were determined for lactate dehydrogenase (LDH) powder produced
      by lyophilization, and two fast freezing processes, spray freeze-drying (SFD) and
      spray freezing into liquid (SFL) nitrogen. The 0.25 mg/mL LDH aqueous feed
      solutions included either 30 or 100 mg/mL trehalose. The SFL process produced
      powders with very high enzyme activities upon reconstitution, similar to
      lyophilization. However, the specific surface area of 13 m(2)/g for SFL was an
      order of magnitude larger than for lyophilization. In SFD activities were reduced
      in the spraying step by the long exposure to the gas-liquid interface for 0.1-1s,
      versus only 2 ms in SFL. The ability to produce stable high surface area
      submicron particles of fragile proteins such as LDH by SFL is of practical
      interest in protein storage and in various applications in controlled release
      including encapsulation into bioerodible polymers. The SFL process has been
      scaled down for solution volumes <1 mL to facilitate studies of therapeutic
      proteins.

PMID- 17027246
TI  - Predictors of asthma control in children from different ethnic origins living in
      Amsterdam.
AB  - To identify factors associated with asthma control in a multi-ethnic paediatric
      population. We interviewed 278 children with paediatrician diagnosed asthma (aged
      7-17 years) and one of their parents. Asthma control was assessed with the Asthma
      Control Questionnaire (ACQ). Detailed information about sociodemographic
      variables, asthma medication, knowledge of asthma, inhalation technique and
      environmental factors were collected. Turkish and Moroccan parents were
      interviewed in their language of choice. Logistic regression analyses were used
      to identify correlates of asthma control. Of the 278 children, 85 (30.6%) were
      Dutch, 84 (30.2%) were Moroccan, 58 (20.9%) were Turkish and 51 (18.3%) were
      Surinamese. Overall, almost 60% had a status of well-controlled asthma, as
      indicated by the ACQ. Only 51 of the 142 (35.9%) Moroccan and Turkish parents had
      a good comprehension of the Dutch language. In logistic regression analyses the
      risk of having uncontrolled asthma was significantly higher among Surinamese
      children (OR 2.3; 95% CI 1.06-4.83), respondents with insufficient comprehension
      of the Dutch language (OR 2.3; 95% CI 1.08-4.78), children using woollen blankets
      (OR 9.8; 95% CI 1.52-63.42), and significantly lower among male (OR 0.5; 95% CI
      0.31-0.91) and non-daily users of inhaled corticosteroids (OR 0.6; 95% CI 0.38
      1.07). In conclusion, ethnicity as well as insufficient comprehension of the
      Dutch language appeared to be independent risk factors for uncontrolled asthma.
      Special attention should be given to children from immigrants groups for example
      by calling in an interpreter by physicians when comprehension is insufficient.

PMID- 17027247
TI  - Incidence and risk factors for ventilator-associated pneumonia in a developing
      country: where is the difference?
AB  - BACKGROUND: Latin America exhibits a wide range of differences, compared to
      developed nations, in genetic background, health services, and clinical research
      development. It is valid to hypothesize that the incidence and risk factors for
      ventilator-associated pneumonia (VAP) in our setting may be substantially
      different of those reported elsewhere. We conducted a study to determine the
      incidence and risk factors for VAP in a University Hospital from Medellin,
      Colombia. METHODS: Prospective cohort study in three intensive care units (ICU)
      (surgical/trauma, medical, cardiovascular) in a 550-bed University Hospital.
      Critically ill patients (n=270) who required at least 48 h of mechanical
      ventilation (MV) between June 2002 and October 2003 were followed until ICU
      discharge, VAP diagnosis or death. RESULTS: Sixty patients (22.2%) developed VAP
      5.9+/-3.6 days after admission. The overall incidence of VAP was 29 cases per
      1000 ventilator-days. The daily hazard for developing VAP increased until day 8,
      and then decreased over the duration of stay in the ICU. The only statistically
      significant factor after multivariable analysis was gender, with being female
      reducing 57% the risk of pneumonia (hazard ratios (HR): 0.43; 95% confidence
      intervals (CI): 0.19-0.96). CONCLUSIONS: The epidemiologic profile of VAP in
      terms of incidence, length of stay and clinical course resembles the general
      pattern described everywhere. Surprisingly, we could not identify any potentially
      modifiable risk factor for VAP. A comprehensive multicenter study is warranted.
      It should provide deep insight about the specific microbiological, genetic and
      clinic features of VAP in our setting.

PMID- 17027248
TI  - Quantifying the availability and the stability of trace cationic elements in fly
      ash.
AB  - For adsorption-desorption controlled leaching processes, the total leachable mass
      and the adsorption constant are parameters representing the availability and the
      stability of trace elements in solid media. With these parameters, one can
      predict the leaching behavior of trace elements from solids under various pH and
      solid-to-liquid ratio conditions. An approach was developed in this paper to
      determine these parameters for model elements Cu(II), Cd(II), and Ni(II) in fly
      ash. This approach consists of a batch equilibrium titration, a batch equilibrium
      leaching with and without target element addition, and mathematical modeling.
      Results indicated that the adsorption constant of a trace element can be
      determined by modeling the adsorption ratio of the added element to the system as
      a function of pH. Results also indicated that the trace element originally
      present in fly ash had similar adsorption-desorption behavior as that added
      externally. By modeling the batch leaching data with and without external element
      addition, the total leachable mass and adsorption constant of the target element
      can be determined simultaneously. The total leachable mass is in agreement with
      experimental data from 50mM EDTA extraction.

PMID- 17027249
TI  - Flexible manipulation of microfluids using optically regulated
      adsorption/desorption of hydrophobic materials.
AB  - To realize highly integrated micro total analysis systems (microTAS), a simply
      controlled miniaturized valve should be utilized on microfluidic device. In this
      paper, we describe the application of photo-induced super-hydrophilicity of
      titanium dioxide (TiO2) to microfluidic manipulation. In addition, we found a new
      phenomenon for reversibly converting the surface wettability using a
      polydimethylsiloxane (PDMS) matrix and the photocatalytic properties of TiO2.
      While PDMS polymer was irradiated with UV, it was confirmed that hydrophobic
      material was released from the polymer to air. Several prepolymers were
      identified as the hydrophobic material with a gas chromatograph and mass
      spectrometer (GC/MS). Here, we successfully demonstrated the flexible
      manipulation of microfluid in a branched microchannel using the reversible
      wettability as micro opto-switching valve (MOS/V). The simultaneous control of
      MOS/Vs was also demonstrated on a 256-MOS/V integrated disk. The MOS/V promises
      to be one of the most effective flow switching valves for advanced applications
      in highly integrated micro/nano fluidics.

PMID- 17027250
TI  - A biomolecule friendly photolithographic process for fabrication of protein
      microarrays on polymeric films coated on silicon chips.
AB  - The last years, there is a steadily growing demand for methods and materials
      appropriate to create patterns of biomolecules for bioanalytical applications.
      Here, a photolithographic method for patterning biomolecules onto a silicon
      surface coated with a polymeric layer of high protein binding capacity is
      presented. The patterning process does not affect the polymeric film and the
      activity of the immobilized onto the surface biomolecules. Therefore, it permits
      sequential immobilization of different biomolecules on spatially distinct areas
      on the same solid support. The polymeric layer is based on a commercially
      available photoresist (AZ5214) that is cured at high temperature in order to
      provide a stable substrate for creation of protein microarrays by the developed
      photolithographic process. The photolithographic material consists of a
      (meth)acrylate copolymer and a sulfonium salt as a photoacid generator, and it is
      lithographically processed by thermal treatment at temperatures <or=50 degrees C,
      development with dilute aqueous basic developer solutions and exposure at
      wavelengths above 300 nm. Following this photolithographic procedure onto the
      polymeric layer coated silicon surface, protein spots with diameters ranging from
      2 to 50 microm were created. The proposed methodology provided good intra-spot
      homogeneity (CV <or=5%) and inter-spot repeatability (CV <or=5%), as it was
      determined through epifluorescence microscopy after reaction of the immobilized
      proteins with their respective fluorescently labeled binding counterparts.
      Moreover, the polymeric film selected for immobilization of biomolecules
      presented high protein binding capacity, which was at least three folds higher
      than that obtained using aminosilanized surfaces. The proposed methodology is
      expected to facilitate considerably the fabrication of dense protein microarrays
      for bioanalytical applications.

PMID- 17027251
TI  - Flexible polyimide microelectrode array for in vivo recordings and current source
      density analysis.
AB  - This work presents implantable, flexible polymer-based probes with embedded
      microelectrodes for acute and chronic neural recordings in vivo, as tested on
      rodents. Acute recordings using this array were done in mice under urethane
      anesthesia and compared to those made using silicon-based probes manufactured at
      the Center for Neural Communication Technology, University of Michigan. The two
      electrode arrays yielded similar results. Recordings with chronically implanted
      polymer-based electrodes were performed for 60 days post-surgically in awake,
      behaving rats. The microelectrodes were used to monitor local field potentials
      and capture laminar differences in function of cortex and hippocampus, and
      produced response waveforms of undiminished amplitude and signal-to-noise ratios
      8 weeks after chronic implantation. The polymer-based electrodes could also be
      connected to a lesion current to mark specific locations in the tissue. Current
      source density (CSD) analysis from the recordings depicted a source - sink
      composition. Tissue response was assessed 8 weeks after insertion by
      immunochemical labeling with glial fibrillary acidic protein (GFAP) to identify
      astrocytes, and histological analysis showed minimal tissue reaction to the
      implanted structures.

PMID- 17027252
TI  - Archaic admixture in the human genome.
AB  - One of the enduring questions in the evolution of our species surrounds the fate
      of 'archaic' forms of Homo. Did Neanderthals go extinct without interbreeding
      with modern humans 25-40 thousand years ago or are their genes present among
      modern-day Europeans? Recent work suggests that Neanderthals and an as yet
      unidentified archaic African population contributed to at least 5% of the modern
      European and West African gene pools, respectively. Extensive sequencing of
      Neanderthal and other archaic human nuclear DNA has the potential to answer this
      question definitively within the next few years.

PMID- 17027253
TI  - TuBaFrost 6: virtual microscopy in virtual tumour banking.
AB  - Many systems have already been designed and successfully used for sharing
      histology images over large distances, without transfer of the original glass
      slides. Rapid evolution was seen when digital images could be transferred over
      the Internet. Nowadays, sophisticated Virtual Microscope systems can be acquired,
      with the capability to quickly scan large batches of glass slides at high
      magnification and compress and store the large images on disc, which subsequently
      can be consulted through the Internet. The images are stored on an image server,
      which can give simple, easy to transfer pictures to the user specifying a certain
      magnification on any position in the scan. This offers new opportunities in
      histology review, overcoming the necessity of the dynamic telepathology systems
      to have compatible software systems and microscopes and in addition, an adequate
      connection of sufficient bandwidth. Consulting the images now only requires an
      Internet connection and a computer with a high quality monitor. A system of
      complete pathology review supporting bio-repositories is described, based on the
      implementation of this technique in the European Human Frozen Tumor Tissue Bank
      (TuBaFrost).

PMID- 17027254
TI  - TuBaFrost 1: Uniting local frozen tumour banks into a European network: an
      overview.
AB  - TuBaFrost is the consortium responsible for the creation of a virtual European
      human frozen tumour tissue bank: a collection of high quality frozen residual,
      accurately classified tumour tissue samples, which are stored in European cancer
      centres and universities. This virtual tissue bank, searchable on the internet,
      has rules for access and use, and a code of conduct to comply with the various
      legal and ethical regulations in European countries. The easy accessibility and
      the European scale of the bank will result in the availability of a large number
      of samples even of rarer tumour types. Standardisation of collection, storage and
      quality control throughout the network is achieved minimising inter-institutional
      variability. A website providing access to upload, search and request samples is
      a key tool of the tissue bank. The search engine makes use of virtual microscopy.
      An overview of the development of the European virtual frozen tissue bank
      infrastructure is described in this paper. The various key aspects are described
      in more detail in a series of articles to appear in this Journal.

PMID- 17027255
TI  - TuBaFrost 2: Standardising tissue collection and quality control procedures for a
      European virtual frozen tissue bank network.
AB  - Tumour Bank Networking presents a great challenge for oncological research as in
      order to carry out large-scale, multi-centre studies with minimal intrinsic bias,
      each tumour bank in the network must have some fundamental similarities and be
      using the same standardised and validated procedures. The European Human Frozen
      Tumour Tissue Bank (TuBaFrost) has responded to this need by the promotion of an
      integrated platform of tumour banks in Europe. The operational framework for
      TuBaFrost has drawn upon the best practice of standard workflows and operating
      procedures employed by members of the TuBaFrost project and key initiatives
      worldwide.

PMID- 17027256
TI  - TuBaFrost 4: access rules and incentives for a European tumour bank.
AB  - When designing infrastructure for a networked virtual tumour bank (samples remain
      at the collector institutes and sample data are collected in a searchable central
      database), it is apparent that this can only function properly after developing
      an adequate set of rules for use and access. These rules must include sufficient
      incentives for the tissue sample collectors to remain active within the network
      and maintain sufficient sample levels in the local bank. These requirements
      resulted in a key TuBaFrost rule, stating that the custodianship of the samples
      remains under the authority of the local collector. As a consequence, the samples
      and the decision to issue the samples to a requestor are not transferred to a
      large organisation but instead remain with the collector, thus allowing
      autonomous negotiation between collector and requestor, potential co-authorship
      in publications or compensation for collection and processing costs. Furthermore,
      it realises a streamlined cost effective network, ensuring tissue visibility and
      accessibility thereby improving the availability of large amounts of samples of
      highly specific or rare tumour types as well as providing contact opportunities
      for collaboration between scientists with cutting edge technology and tissue
      collectors. With this general purpose in mind, the rules and responsibilities for
      collectors, requestors and central office were generated.

PMID- 17027257
TI  - A feasibility study of the efficacy and tolerability of the combination of
      Exemestane with the COX-2 inhibitor Celecoxib in post-menopausal patients with
      advanced breast cancer.
AB  - BACKGROUND: This was a feasibility study of the combination of Exemestane and the
      cyclooxygenase-2 (COX-2) inhibitor Celecoxib in advanced breast cancer. PATIENTS
      AND METHODS: Post-menopausal women with histologically proven, hormone receptor
      positive, advanced breast cancer who had progressive disease, normal blood
      counts, liver and renal function were eligible. Exemestane was given at a dose of
      25 mg daily and Celecoxib at a dose of 400 mg bd. Responses were assessed
      according to RECIST criteria and toxicity was accessed according to CTC. The
      primary end-point was the percentage of patients who had neither discontinued
      therapy nor progressed at 6 months ('treatment successes'). RESULTS: Fifty-three
      eligible patients were enrolled. Of 30 patients with target lesions, 4 (13%) had
      a complete response (CR), 12 (40%) a partial response (PR) and 5 (17%) stable
      disease (SD). The best response in 18 of the 23 patients with no target lesions
      at baseline was stable disease. The clinical benefit (CR, PR+SD) for the whole
      group was therefore 39/53 (74%). The 'treatment success' rate was 60%. There were
      two non-malignant deaths which may have been associated with treatment.
      CONCLUSION: The combination of Exemestane and Celecoxib shows promising activity
      and tolerability and these results support the use of this combination in phase
      III clinical trials of short duration treatments.

PMID- 17027258
TI  - Development of luciferase tagged brain tumour models in mice for chemotherapy
      intervention studies.
AB  - The blood-brain barrier (BBB) is considered one of the major causes for the low
      efficacy of cytotoxic compounds against primary brain tumours. The aim of this
      study was to develop intracranial tumour models in mice featuring intact or
      locally disrupted BBB properties, which can be used in testing chemotherapy
      against brain tumours. These tumours were established by intracranial injection
      of suspensions of different tumour cell lines. All cell lines had been
      transfected with luciferase to allow non-invasive imaging of tumour development
      using a super-cooled CCD-camera. Following their implantation, tumours developed
      which displayed the infiltrative, invasive or expansive growth patterns that are
      also found in primary brain cancer or brain metastases. Contrast-enhanced
      magnetic resonance imaging showed that the Mel57, K1735Br2 and RG-2 lesions grow
      without disruption of the BBB, whereas the BBB was leaky in the U87MG and VEGF-A
      transfected Mel57 lesions. This was confirmed by immunohistochemistry.
      Bioluminescence measurements allowed the visualisation of tumour burden already
      within 4 days after injection of the tumour cells. The applicability of our
      models for performing efficacy studies was demonstrated in an experiment using
      temozolomide as study drug. In conclusion, we have developed experimental brain
      tumour models with partly disrupted, or completely intact BBB properties. In vivo
      imaging by luciferase allows convenient follow-up of tumour growth and these
      models will be useful for chemotherapeutic intervention studies.

PMID- 17027259
TI  - Improvement of carbonyl reductase production of Geotrichum candidum for the
      transformation of 1-acetonaphthone to S(-)-1-(1'-napthyl) ethanol.
AB  - The aim of this work was to study the influence of media components and physico
      chemical parameters on the growth and carbonyl reductase production by Geotrichum
      candidum. Under optimized conditions, the conversion of the substrate increased
      to >93%, while the specific growth rate and enzyme activity were increased by
      200% and 29%, respectively. The rate of conversion of the substrate was also very
      high in the cells grown in optimized medium. The volumetric productivity of the
      biotransformation process was much higher (0.27g/lh) with the cells grown in the
      optimized medium compared to that of grown in un-optimized medium (0.16g/lh). The
      cells were also highly stable in the operational condition, indicating the
      feasibility of their use in multiple batches of reaction.

PMID- 17027260
TI  - Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno
      and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation
      targeting angiogenetic kinases.
AB  - A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been
      designed based on pharmacophore models of ATP competitive kinase inhibitors.
      Versatile synthetic methods via double Suzuki coupling to explore SAR have been
      established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2,
      and EphB4, have been successfully discovered.

PMID- 17027261
TI  - Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor
      alpha converting enzyme (TACE).
AB  - Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of
      selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was
      discovered. Optimization of initial lead 1 resulted in a potent inhibitor (51),
      with an IC(50) of 2 nM in a porcine TACE assay. To the best of our knowledge,
      compound 51 and related analogues represent first examples of non-hydroxamate
      based inhibitors of TACE with single digit nanomolar potency.

PMID- 17027262
TI  - Discovery and initial development of a novel class of antibacterials: inhibitors
      of Staphylococcus aureus transcription/translation.
AB  - The novel bacterial transcription/translation (TT) inhibitor 1 was identified
      through a combination of high throughput screening and exploratory medicinal
      chemistry. Initial optimization of the anthranilic acid moiety and sulfonamide
      amine diversity was accomplished via 1- and two-dimensional solution phase
      libraries, resulting in an improvement in the MIC of the lead from 64 to 8mug/mL
      (compound 4l). Subsequent modification of the central aromatic ring and further
      refinement of the sulfonamide amines required the development of a solid phase
      route on Wang resin. The resulting libraries generated a number of potent
      antibacterials with MICs of 1mug/mL (e.g., 10b, 12, and 13). During the course of
      this work, it became apparent that the antibacterial activity of the series is
      not fully correlated with TT inhibition, suggesting that at least one additional
      mechanism of action is operative.

PMID- 17027263
TI  - Identification of novel, orally bioavailable spirohydantoin CGRP receptor
      antagonists.
AB  - A rapid analogue approach to identification of spirohydantoin-based CGRP
      antagonists provided novel, low molecular weight leads. Modification of these
      leads afforded a series of nanomolar benzimidazolinone-based CGRP receptor
      antagonists. The oral bioavailability of these antagonists was inversely
      correlated with polar surface area, suggesting that membrane permeability was a
      key limitation to absorption. Optimization provided compound 12, a potent CGRP
      receptor antagonist (K(i)=21nM) with good oral bioavailability in three species.

PMID- 17027264
TI  - New pyrimido[5,4-b]indoles and [1]benzothieno[3,2-d]pyrimidines: high affinity
      ligands for the alpha(1)-adrenoceptor subtypes.
AB  - A number of new pyrimido[5,4-b]indole and [1]benzothieno[3,2-d]pyrimidine
      derivatives were synthesized and evaluated for their binding and functional
      properties at alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes. They behaved
      as potent alpha(1)-AR antagonists. In binding experiments, some of them (RC24 and
      RC23) showed very high affinity for the alpha(1D)-AR subtype.

PMID- 17027265
TI  - Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4
      b]quinoxalines.
AB  - A new series of 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4
      b]quinoxalines was synthesized and submitted to antibacterial and antifungal
      activities. Result of the antimicrobial screening showed the compound 4j being
      the most effective among the various treatments in antimicrobial screening.
      Compounds 4c, 4d, 4k, and 4l showed moderate activity against the microorganisms
      tested.

PMID- 17027266
TI  - Binding affinity prediction of non-peptide inhibitors of HIV-1 protease using
      COMBINE model introduced from peptide inhibitors.
AB  - Comparative binding energy (COMBINE) analysis method is one of the QSAR
      techniques for the prediction of biological activities of inhibitors based on
      interaction energies between ligands and proteins decomposed into each amino acid
      residue. We supposed that the predictive ability of the COMBINE method does not
      depend essentially on the molecular frameworks of ligands. To verify this idea,
      we performed the COMBINE analysis of non-peptide inhibitors of HIV-1 protease
      (HIVp), where the prediction model was constructed using inhibitors with a
      peptide scaffold as a training set. The predictive performance of the AMBER and
      CHARMm force fields was very high and at the same level (q(2)=0.75, 0.67,
      SDEP(cv)=0.76, 0.89, and SDEP(ex)=0.92, 0.66, respectively). The high predictive
      ability of the COMBINE method for the distinct scaffold compounds is due to the
      informative description of the interaction energies for compounds that are
      located at the binding site. This result suggests that COMBINE analysis may be
      applied not only to the lead optimization stage but also to the lead evolution
      stages.

PMID- 17027267
TI  - Design, synthesis, and biological evaluation of new (2E,6E)-10-(dimethylamino)
      3,7-dimethyl-2,6-decadien-1-ol ethers as inhibitors of human and Trypanosoma
      cruzi oxidosqualene cyclase.
AB  - New dimethylamino truncated squalene ether derivatives containing a different
      aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic)
      group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of
      the sterol biosynthetic pathway. The activity against human OSC was compared with
      the activity against the OSCs of pathogenic organisms such as Pneumocystis
      carinii and Trypanosoma cruzi. The phenyl derivative was the most potent
      inhibitor of T. cruzi OSC.

PMID- 17027268
TI  - New antifungal flavonoid glycoside from Vitex negundo.
AB  - Flavonoids are ubiquitous in photosynthesizing cells and are common part of human
      diet. For centuries, preparations containing these compounds as the principal
      physiologically active constituents have been used to treat human diseases.
      Increasingly, this class of natural products is becoming the subject of anti
      infective research. Our bioactivity guided fractionation of ethanolic extract of
      leaves of Vitex negundo resulted in the isolation of new flavone glycoside (4)
      along with five known compounds 1-3, 5 and 6. All the isolated compounds were
      evaluated for their antimicrobial activities. The new flavone glycoside 4 and
      compound 5 were found to have significant antifungal activity against
      Trichophyton mentagrophytes and Cryptococcus neoformans at MIC 6.25 microg/ml.

PMID- 17027269
TI  - Arylsulfonamides as a new class of cannabinoid CB1 receptor ligands:
      identification of a lead and initial SAR studies.
AB  - High-throughput screening of the UCB sample collection identified the piperidinyl
      sulfonyl benzoic ester 1 as a novel agonist for CB(1) receptor with nanomolar
      affinity. We report here the pharmacological profile of compound 1 as well as
      preliminary biological activities in pain model. Diverse close analogs of 1 were
      purchased and the structure-affinity relationships among this novel class are
      discussed.

PMID- 17027270
TI  - Improved 3D-QSAR CoMFA of the dopamine transporter blockers with multiple
      conformations using the genetic algorithm.
AB  - A 3D-QSAR/CoMFA was performed for a series of 42 piperidine-based dopamine
      transporter (DAT) blockers. The overall process consisted of three major steps:
      (1) a pharmacophore model was built using the Genetic Algorithm Similarity
      Program (GASP); (2) the Flexible Superposition (FlexS) technique was applied to
      generate multiple conformations for each of the ligands based on the
      pharmacophore; (3) the Genetic Algorithm was employed to optimize the selection
      of the ligand conformations for the CoMFA modeling. The CoMFA models were found
      to be more detailed in the putative binding site by exploring multiple
      conformations of each ligand. The comparison of the contour maps shows that, in
      general, these models are comparable and the differences between them result from
      the ability of the flexible 3alpha-substituents of the ligands to adopt multiple
      conformations satisfying the same pharmacophore model. These findings provide
      guidance for the design and improvement of compounds with DAT activity, which is
      important for the development of a treatment of cocaine addiction and certain
      neurological disorders.

PMID- 17027271
TI  - Natural inhibitors targeting osteoclast-mediated bone resorption.
AB  - Human cathepsin K, matrix metalloproteinase 9, and alpha(V)beta(3) integrin are
      the key regulators in osteoclast-mediated bone resorption. In this paper, we
      found natural inhibitors 1-10 for them by enzyme inhibition assays. Inhibitors 1
      7, 8-9, and 10 are novel inhibitors of human cathepsin K, matrix
      metalloproteinase 9, and alpha(V)beta(3), respectively.

PMID- 17027272
TI  - SAR studies of 6-(arylamino)-4,4-disubstituted-1-methyl-1,4-dihydro
      benzo[d][1,3]oxazin-2-ones as progesterone receptor antagonists.
AB  - We previously disclosed that 6-aryl benzoxazin-2-ones were PR modulators. In a
      continuation of this work we examined the SAR of new 6-arylamino benzoxazinones
      and found the targets 1-25, with an extra amino linker between the pendent 6-aryl
      groups and benzoxazinone or benzoxazine-2-thione core, were PR antagonists. A
      series of compounds with substituents at the 1- and 4-positions as well as
      different 6-aryl groups were prepared and tested in the T47D cell alkaline
      phosphatase assay. Interestingly, the SAR unveiled from the 6-arylamino
      benzoxazinones was quite different from those of their parent compounds. For
      example, in contrast to the 6-aryl benzoxazinones, methyl substitution at the 1
      position significantly increased the potency of 6-arylamino benzoxazinones.
      Several 6-arylamino benzoxazinones (e.g., 12, IC(50)=5.0 nM) had low nanomolar in
      vitro potency as PR antagonists in the T47D cell alkaline phosphatase assay.

PMID- 17027273
TI  - CLOCK leaves its mark on histones.
AB  - Transcriptional regulation of circadian rhythms in mammals involves a negative
      feedback loop whereby a CLOCK-BMAL1 complex activates transcription of the genes
      encoding the proteins PER1 (Period 1), PER2, CRY1 (Cryptochrome 1) and CRY2,
      which feed back to inhibit the activity of CLOCK-BMAL1. It is becoming evident
      that chromatin remodeling has a crucial role in the transcriptional regulation of
      genes governing circadian rhythms. This is highlighted in a recent report that
      shows that CLOCK has histone acetyltransferase activity, thus, demonstrating that
      molecular components of the biological clock can themselves catalyze chromatin
      modifications.

PMID- 17027274
TI  - Determinants of drug brain uptake in a rat model of seizure-associated
      malformations of cortical development.
AB  - We examined the blood-brain barrier (BBB) function in methylazoxymethanol acetate
      (MAM)-treated rats, a model of human developmental brain malformations. We found
      aberrant vessels morphology and serum albumin leakage in the heterotopic
      (malformed) hippocampus; these changes were associated with a significant
      increase in endothelial P-glycoprotein (P-gp) expression. Seizures exacerbated
      BBB leakage and greatly augmented P-gp expression in vessels and additionally in
      perivascular/parenchymal astrocytes. The effects of seizures were observed to a
      much larger extent in malformed than in normal brain tissue. The intrinsic
      changes in BBB function in MAM-exposed rats were associated with increased blood
      to-brain penetration of ondansetron, a P-gp substrate. However, a marked
      reduction in drug brain levels was provoked by seizures, and this effect was
      reversed by selective blockade of P-gp activity with tariquidar. Changes in BBB
      function may critically contribute to determine the brain uptake and distribution
      of P-gp substrates in epileptic tissue associated with developmental
      malformations.

PMID- 17027275
TI  - Interleukin-1beta mediates GDNF up-regulation upon dopaminergic injury in ventral
      midbrain cell cultures.
AB  - We recently proposed the involvement of diffusible modulators in signalling
      astrocytes to increase glial cell line-derived neurotrophic factor (GDNF)
      expression after selective dopaminergic injury by H2O2 or L-DOPA. Here we report
      that interleukin-1beta (IL-1beta) is involved in this crosstalk between injured
      neurons and astrocytes. IL-1beta was detected only in the media from challenged
      neuron-glia cultures. Exogenous IL-1beta did not change GDNF protein levels in
      astrocyte cultures, and diminished GDNF levels in neuron-glia cultures. This
      decrease was not due to cell loss, as assessed by the MTT assay and
      immunocytochemistry. Neither H2O2 nor L-DOPA induced microglia proliferation or
      appeared to change its activation state. The IL-1 receptor antagonist (IL-1ra)
      prevented GDNF up-regulation in challenged cultures, showing that IL-1beta is
      involved in the signalling between injured neurons and astrocytes. Since IL-1ra
      decreased the number of dopaminergic neurons in H2O2-treated cultures, we propose
      that IL-1 has a neuroprotective role in this system involving GDNF up-regulation.

PMID- 17027276
TI  - Characterization of plant phenotypes associated with loss-of-function of AtCNGC1,
      a plant cyclic nucleotide gated cation channel.
AB  - Of the 57 cation channel genes in the Arabidopsis genome, over a third encode
      cyclic nucleotide gated cation channels (CNGCs). CNGCs are ion channels regulated
      by cytosolic signaling molecules (cyclic nucleotides, calmodulin, and Ca(2+)),
      and which conduct Ca(2+) as well as K(+) and in some cases Na(+). Little is
      currently known about the role CNGCs may play in plant growth and development.
      Here, we examined the hypothesis that an Arabidopsis thaliana genotype containing
      a null mutation in one of the CGNC genes (AtCNGC1) would display cation uptake
      related growth phenotype differences from wild type (WT) plants. We determined
      that AtCNGC1 protein is primarily expressed in the roots of Arabidopsis
      seedlings. Seedlings lacking this protein had slightly (6-22%) lower shoot Ca(2+)
      than WT plants. Primary roots of Atcngc1 mutant seedlings grew faster than roots
      of WT plants, and had larger angles of gravicurvature and less nitric oxide
      generation upon gravistimulation. We conclude that channels formed (at least in
      part) by AtCNGC1 contribute (along with other channels) to Ca(2+) uptake into
      plants, and that Ca(2+) uptake into roots through AtCNGC1 affects some aspects of
      growth in the primary root of Arabidopsis seedlings.

PMID- 17027277
TI  - Risk factors for mortality and hospital re-admission after surgical ventricular
      restoration.
AB  - BACKGROUND: Surgical ventricular restoration is an option in patients with
      coronary artery disease, heart failure, postinfarction left ventricular aneurysm
      or ischemic dilated cardiomyopathy with or without ventricular tachycardia. The
      aims of this study were to investigate survival and re-admission for heart
      failure and to identify predictors for early and long-term mortality and re
      admission after surgical ventricular restoration. METHODS: Pre- and postoperative
      data were collected for 136 consecutive patients who underwent surgical
      ventricular restoration for postinfarction left ventricular aneurysm or ischemic
      dilated cardiomyopathy during 1994-2005. Survival and risk factors for mortality
      and hospital re-admission were analyzed by using multivariable models. RESULTS:
      Early mortality was 10/136 (7.4%). At 1, 3, 5 and 9 years overall actuarial
      survival was 89%, 80%, 68% and 62%. Increasing age, diabetes and mitral
      regurgitation grade III-IV were associated with an increased risk for late
      mortality. Freedom from re-hospitalization due to heart failure or cardiac death
      in operative survivors at 1, 3 and 5 years was 78%, 72% and 58%. Risk factors for
      re-hospitalization or cardiac death in operative survivors were increasing age
      and increasing grade of mitral regurgitation. CONCLUSIONS: Surgical ventricular
      restoration by the Dor procedure can achieve good long-term survival and a high
      degree of freedom from readmission for heart failure in patients with advanced
      ischemic heart disease. We found a strong association between increasing grade of
      mitral regurgitation and both long-term mortality and re-admission for heart
      failure.

PMID- 17027278
TI  - Glioblastoma in the elderly: current and future trends.
AB  - Data from a prospective trial large enough to provide a reliable analysis of
      outcome and prognostic factors in elderly patients with glioblastoma (GBM) are
      not yet available in the literature. Extensive tumor removal appears to offer
      patients the best possible chance of a speedy neurological recovery. Adequate
      radiotherapy (RT) should always be given to elderly patients if they have
      undergone gross total debulking and have maintained a good performance status. It
      is, however important to bear in mind that the risk of long-term cognitive
      impairment may be higher in patients on high-dose RT and that a short course of
      accelerated RT can achieve the same survival. Rather than being ruled out on
      principle, chemotherapy should be considered on the basis of an accurate
      assessment of the factors that might compromise the individual patient's
      tolerance to drugs administered. Temozolomide appears to be the best available
      chemotherapy in this population of patients.

PMID- 17027279
TI  - Should concomitant and adjuvant treatment with temozolomide be used as standard
      therapy in patients with anaplastic glioma?
AB  - Malignant gliomas are devastating tumors associated with poor prognosis. Standard
      treatment has been surgery followed by radiotherapy while the role of
      chemotherapy has remained controversial. Concomitant and adjuvant treatment with
      temozolomide has recently been shown to improve survival in patients with
      glioblastoma. While it seems intuitive to apply this regimen to patients with
      anaplastic gliomas which have traditionally been considered more chemosensitive,
      chemotherapy has not been shown to prolong life in patients with anaplastic
      gliomas. Despite promising preclinical and early clinical results, there is
      currently not enough level 1 evidence to justify concomitant and adjuvant
      temozolomide as standard therapy for patients with newly diagnosed anaplastic
      gliomas. Further investigation is needed to better define the role of
      chemotherapy in patients with anaplastic gliomas. Trials evaluating
      chemoradiotherapy as well as targeted therapeutic agents are the subject of
      further research.

PMID- 17027280
TI  - Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its
      correlation with disease activity.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease
      characterized by a wide variety of autoantibodies, some of which are pathogenic.
      In recent years it has become more evident that the polyclonal B cell activation
      in SLE is T-cell dependent. The stimulation of the autoantibody producing B cells
      is likely mediated by the TH2 subtype of T cells producing IL-4, IL-5, IL-6 and
      IL- 10, whereas the TH1 subtype secreting IL-2 and IFN-gamma predominates in cell
      mediated immune response. Tumor Necrosis Factor (TNF-alpha) is both a
      proinflammatory and an immunoregulatory cytokine. TNF-alpha has differential
      effects on B cells, on T cells and on dendritic cells as well as on the process
      of programmed cell death. Understanding how the immune system integrates the
      pleiotropic properties of TNF-alpha is a challenge, particularly so in diseases
      like SLE. Meanwhile the role of IL-6 in the pathogenesis of SLE is controversial.
      OBJECTIVE: To investigate whether serum levels of TNF-alpha and IL-6 is higher in
      Egyptian patients with SLE than healthy control volunteers and its correlation
      with the clinical activity in patients with different activity scores as measured
      by Systemic Lupus Erythmatosus Disease Activity Index (SLEADI). METHODS: Sixty
      individuals (40 patients with Systemic lupus Erythmatosus and 20 healthy control
      volunteers) were the subject of this study, they were subjected to thorough
      clinical examination, laboratory investigations, their clinical disease activity
      was scored according to SLEDAI, and serum sampling was obtained for TNF-alpha and
      IL-6 levels assay. Renal biopsy was carried out and examined by light microscopy
      by a pathologist blinded with the clinical activity. RESULTS: The mean level of
      TNF-alpha was (766.95+/-357.82Pg/ml) for patients with active disease while it
      was (314.01+/-100.87Pg/ml) for those with inactive disease and (172.7+/
      39.19Pg/ml) for the healthy control group. The difference was statistically
      significant (P=.002). The mean level of IL-6 was (135.4+/-54.23Pg/ml) for
      patients with active disease while it was (47.33+/-18.61Pg/ml) for those with
      inactive disease and (21.15+/-10.99Pg/ml) for the healthy control group. The
      difference was statistically significant (P=.002). A significant correlations
      between TNF-alpha and IL-6 serum levels and the SLEDAI score was observed (r=.743
      and .772, respectively). CONCLUSION: Serum TNF-alpha and IL-6 are sensitive
      markers of SLE disease activity. They may be useful independent markers for
      prediction of SLE disease activity and to differentiate normal subjects from
      those having SLE. Possible therapeutic implications in the treatment of SLE in
      the future deserve wide scale trials.

PMID- 17027281
TI  - The role of the CD95, CD38 and TGFbeta1 during active human cytomegalovirus
      infection in liver transplantation.
AB  - AIM: Human cytomegalovirus (HCMV) has highly evolved mechanisms for avoiding
      detection by the host immune system. The aim of this study was to analyze the
      expression levels of TGFbeta1, soluble form of CD95, CD95 ligand (sCD95 and
      sCD95L, respectively) in plasma and CD95 expression on CD3(+) cells, CD38
      expression on CD8(+) cells in liver transplanted recipients with active HCMV
      infection. METHODS: Blood samples were collected from 15 liver transplanted
      recipients with active HCMV infection and 15 recipients without HCMV infection.
      CD95 expression on CD3(+) cells and CD38 expression on CD8(+) cells were
      quantitatively detected with two-color fluorescence activated cell sorter (FACS)
      analysis. Lymphocyte surface phenotypes of CD4 and CD8 were detected with FACS
      analysis. Plasma sCD95, sCD95L and TGFbeta1 levels were determined with enzyme
      linked-immuno-sorbent assay (ELISA). The results were compared with that from 15
      healthy individuals. RESULTS: CD95 expression on CD3(+) T-cells and CD38
      expression on CD8(+) cells were significantly increased in active HCMV infection
      group compared with that in stable group or healthy group (P<0.01). No
      significant difference was seen between stable group and healthy group (P>0.05).
      The percentages of CD4(+) T-cell and CD4/CD8 ratio in active HCMV infection group
      were significantly lower than the values in stable group and healthy group
      (P<0.05). Plasma levels of TGFbeta1 and sCD95 were significantly increased in
      active HCMV infection group compared to stable group and healthy group (P<0.05).
      In contrast, plasma levels of sCD95L in healthy group were not significantly
      different from that expressed in active HCMV infection group and stable group
      (P>0.05). CONCLUSION: HCMV suppress proliferation of activated T cells by
      apoptosis and by releasing immunosuppressive cytokine TGFbeta1. This may provide
      an important clue to a better understanding of the pathogenesis in liver
      transplanted recipients with active HCMV infection.

PMID- 17027282
TI  - One-step affinity purification of recombinant urokinase-type plasminogen
      activator receptor using a synthetic peptide developed by combinatorial
      chemistry.
AB  - Several lines of evidence have pointed to a role of urokinase-type plasminogen
      activator receptor (uPAR) as a modulator of certain biochemical processes that
      are active during tumor invasion and metastasis. Consequently, the structure and
      function of this receptor have been studied extensively, using recombinantly
      produced uPAR that has been purified by either affinity chromatography using its
      cognate ligand, the urokinase-type plasminogen activator (uPA), or a monoclonal
      anti-uPAR antibody (R2), or by hydroxyapatite. Here, we present a new method for
      the efficient one-step affinity purification of recombinant uPAR exploiting a
      high-affinity synthetic peptide antagonist (AE152). The corresponding parent
      peptide was originally identified in a random phage-display library and
      subsequently subjected to affinity maturation by combinatorial chemistry. This
      study compares the affinity purification of a soluble, recombinant uPAR using the
      monoclonal antibody R2 or the peptide AE152 immobilized on Sepharose. The two
      affinity ligands perform equally well in purifying uPAR from Drosophila
      melanogaster Schneider 2 cell culture medium and yield products of comparable
      purity, activity, and stability as judged by SDS-PAGE, size exclusion
      chromatography and surface plasmon resonance analysis. The general availability
      of peptide synthesis renders the present AE152-based affinity purification of
      uPAR more accessible than the traditional protein-based affinity purification
      strategies. In this way, large amounts of recombinant uPAR can conveniently be
      purified for further structural and functional studies.

PMID- 17027283
TI  - Preparation and characterization of recombinant protein ScFv(CD11c)-TRP2 for
      tumor therapy from inclusion bodies in Escherichia coli.
AB  - Dendritic cells (DCs)-based immunotherapy represents an approach to the
      prevention and treatment of cancers. Targeting antigens to receptors on DCs can
      be expected to enhance immune response. We have constructed an expression vector
      pET32a(+)-ScFv(CD11c)-TRP2 based on a single-chain antibody fragment (ScFv) that
      targets the high affinity receptor CD11c which is expressed on murine DCs. The 3'
      terminal end of the ScFv was ligated to the gene for MHC class I molecule
      recognized peptide from mouse tyrosine-related protein 2 (TRP2). Using this
      vector, we have expressed and purified ScFv(CD11c)-TRP2, a fusion protein that
      could target TRP2 peptide to CD11c on DCs in vivo to elicit anti-tumor responses.
      This fusion protein was expressed in inclusion bodies in Escherichia coli
      BL21(DE3) and was refolded and purified on-column effectively by immobilized
      metal affinity chromatography using His-tag. Flow cytometry assays showed the
      specific binding ability of ScFv(CD11c)-TRP2 to DCs, which could be blocked by a
      hamster anti-mouse CD11c produced by N418 hybridoma. Further studies demonstrated
      that ScFv(CD11c)-targeted TRP2 peptide processed by DCs was capable of
      stimulating T cells proliferation. Thus, this fusion protein provides a basis for
      further research in cancer therapy in vivo.

PMID- 17027284
TI  - Estimating osteoarthritis incidence from population-based administrative health
      care databases.
AB  - PURPOSE: The aim of the study is to develop a method to estimate osteoarthritis
      (OA) incidence by using administrative health care databases. METHODS: Using
      actual counts of OA diagnoses in different periods, we generated an equation that
      estimated the number of new OA diagnoses based on the length of time used for
      excluding prevalent OA cases. Physicians billing files from 1983 to 2002
      maintained at Alberta Health and Wellness were used to verify the proposed
      method. Age- and sex-specific and crude OA incidences in 2002 were calculated by
      using this method. RESULTS: Women aged 50 to 59 years had the greatest incidence.
      For men, the greatest incidence was in the 60- to 69-year age category. Crude
      incidences for women and men were 1103 and 934 per 100,000 person-years,
      respectively. The overall crude rate was 1040 per 100,000 person-years.
      CONCLUSIONS: Modified power function accurately summarizes the relationship
      between number of first OA diagnoses and length of the clearance period and thus
      provides an effective model to estimate OA incidence. Not restricted to OA, this
      model also can be implemented to estimate incidences of other chronic conditions.

PMID- 17027285
TI  - Weight, height, and body mass index and risk for ovarian cancer in a cohort
      study.
AB  - PURPOSE: Reported associations between ovarian cancer and body size are
      inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer
      Detection Demonstration Project Follow-Up Study. METHODS: The 46,026 participants
      completed a baseline interview and mailed questionnaires between 1979 and 1998.
      By using multiple sources, we identified 346 incident ovarian cancers during
      follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to
      estimate relative risks for developing ovarian cancer associated with height and
      weight (measured 1973 to 1980) and self-reported current and usual adult weight
      (collected during follow-up). RESULTS: Neither taller height (> or =66 versus <62
      inches; RR, 0.90; 95% CI, 0.64-1.26) nor greater weight (> or =161 versus < or
      =120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer.
      Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)),
      overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% CI, 0.78-1.29) and obesity
      (BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1.48) were not associated with
      ovarian cancer. Severe obesity (BMI > or = 35 kg/m(2)) produced a
      nonsignificantly elevated RR (1.55; 95% CI, 0.84-2.84). Associations with
      histologic types and statistical interactions with menopausal status and hormone
      therapy use were null. CONCLUSIONS: Based on height and weight measured before
      baseline, overweight and obesity were not significantly associated with ovarian
      cancer in this cohort.

PMID- 17027286
TI  - Match rate and positional accuracy of two geocoding methods for epidemiologic
      research.
AB  - PURPOSE: This study compares the match rate and positional accuracy of two
      geocoding methods: the popular geocoding tool in ArcGIS 9.1 and the Centrus
      GeoCoder for ArcGIS. METHODS: We first geocoded 11,016 Texas addresses in a case
      control study using both methods and obtained the match rate of each method. We
      then randomly selected 200 addresses from those geocoded by using both methods
      and obtained geographic coordinates of the 200 addresses by using a global
      positioning system (GPS) device. Of the 200 addresses, 110 were case maternal
      residence addresses and 90 were control maternal residence addresses. These GPS
      surveyed coordinates were used as the "true" coordinates to calculate positional
      errors of geocoded locations. We used Wilcoxon signed rank test to evaluate
      whether differences in positional errors from the two methods were statistically
      significantly different from zero. In addition, we calculated the sensitivity and
      specificity of the two methods for classifying maternal addresses within 1500 m
      of toxic release inventory facilities when distance is used as a proxy of
      exposure. RESULTS: The match rate of the Centrus GeoCoder was more than 10%
      greater than that of the geocoding tool in ArcGIS 9.1. Positional errors with the
      Centrus GeoCoder were less than those of the geocoding tool in ArcGIS 9.1, and
      this difference was statistically significant. Sensitivity and specificity of the
      two methods are similar. CONCLUSIONS: Centrus GeoCoder for ArcGIS for geocoding
      gives greater match rates than the geocoding tool in ArcGIS 9.1. Although the
      Centrus GeoCoder has better positional accuracy, both methods give similar
      results in classifying maternal addresses within 1500 m of toxic release
      inventory facilities when distance is used as a proxy of exposure.

PMID- 17027287
TI  - Confounder selection in environmental epidemiology: assessment of health effects
      of prenatal mercury exposure.
AB  - PURPOSE: The purpose of the study is to compare different approaches to the
      identification of confounders needed for analyzing observational data. Whereas
      standard analysis usually is conducted as if the confounders were known a priori,
      selection uncertainty also must be taken into account. METHODS: Confounders were
      selected by using backward elimination (BE), change in estimate (CIE) method,
      Akaike information criterion, Bayesian information criterion (BIC), and an
      empirical approach using a priori information. A modified ridge regression
      estimator, which shrinks effects of confounders toward zero, also was considered.
      For each criterion, uncertainty in the estimated exposure effect was assessed by
      using bootstrap simulations for which confounders were selected in each sample.
      These methods were illustrated by using data for mercury neurotoxicity in Faroe
      Islands children. Point estimates and standard errors of mercury effects on
      confounder-sensitive neurobehavioral outcomes were calculated for each selection
      procedure. RESULTS: The full model and the empirical a priori model showed
      approximately the same precision, and these methods were (slightly) inferior to
      only modified ridge regression. Lower precisions were obtained by using BE with a
      low cutoff level, BIC, and CIE. CONCLUSIONS: Standard analysis ignores model
      selection uncertainty and is likely to yield overoptimistic inferences. Thus, the
      traditional BE procedure with p = 5% should be avoided. If data-dependent
      procedures are required for confounder identification, we recommend that
      inferences be based on bootstrap statistics to describe the selection process.

PMID- 17027288
TI  - Cognitive functioning in late life: the impact of moderate alcohol consumption.
AB  - PURPOSE: Sex differences in the association between moderate alcohol consumption
      and cognitive functioning were examined during 4 years. METHODS: Participants
      were 2716 US older adults 70 years and older (mean age, = 76.02 years) who were
      free of cognitive impairment from the Second Longitudinal Study of Aging (1994 to
      2000). Multiple logistic regression models were used to predict cognitive
      functioning (adapted Telephone Interview for Cognitive Status) from average daily
      alcohol intake (no drink, one drink or less daily, and more than one drink daily)
      during 4 years after controlling for covariates. RESULTS: Sex differences in the
      association between alcohol consumption and cognitive functioning were found (p <
      0.01). Older adults with alcohol consumption of one drink or less per day had a
      lower odds of low cognitive functioning compared with abstainers for women
      (adjusted odds ratio [AOR], 0.67; 95% confidence interval [CI], 0.55-0.83), but
      not men (AOR, 0.96; 95% CI, 0.69-1.34). CONCLUSIONS: For older adults with a
      level of cognitive functioning within normal ranges, moderate amounts of alcohol,
      an average of one drink or less daily, was protective for women, but not men.
      Caution should be used in suggesting moderate alcohol consumption to maintain
      cognitive functioning because of the risks of consuming alcohol.

PMID- 17027289
TI  - Modeling adolescent drug-use patterns in cluster-unit trials with multiple
      sources of correlation using robust latent class regressions.
AB  - PURPOSE: The purpose of the study is to examine variation in adolescent drug-use
      patterns by using latent class regression analysis and evaluate the properties of
      an estimating-equations approach under different cluster-unit trial designs.
      METHODS: A set of second-order estimating equations for latent class models under
      the cluster-unit trial design are proposed. This approach models the correlation
      within subclusters (drug-use behaviors), but ignores the correlation within
      clusters (communities). A robust covariance estimator is proposed that accounts
      for within-cluster correlation. Performance of this approach is addressed through
      a Monte Carlo simulation study, and practical implications are illustrated by
      using data from the National Evaluation of the Enforcing Underage Drinking Laws
      Randomized Community Trial. RESULTS: The example shows that the proposed method
      provides useful information about the heterogeneous nature of drug use by
      identifying two subtypes of adolescent problem drinkers. A Monte Carlo simulation
      study supports the proposed estimation method by suggesting that the latent class
      model parameters were unbiased for 30 or more clusters. Consistent with other
      studies of generalized estimating equation (GEE) estimators, the robust
      covariance estimator tended to underestimate the true variance of regression
      parameters, but the degree of inflation in the test size was relatively small for
      70 clusters and only slightly inflated for 30 clusters. CONCLUSIONS: The proposed
      model for studying adolescent drug use provides an alternative to standard
      diagnostic criteria, focusing on the nature of the drug-use profile, rather than
      relying on univariate symptom counts. The second-order GEE-type estimation
      procedure provided a computationally feasible approach that performed well for a
      moderate number of clusters and was consistent with prior studies of GEE under
      the generalized linear model framework.

PMID- 17027290
TI  - Impact of hysterectomy and bilateral oophorectomy on race-specific rates of
      corpus, cervical, and ovarian cancers in the United States.
AB  - PURPOSE: Population-based cancer incidence rates of the corpus uteri, cervix
      uteri, and ovaries are underestimated if they fail to remove women not at risk
      for developing the cancers from the denominator in the race calculation. This
      study compares incidence rates among selected racial groups for these cancers
      before and after correction for prevalence of hysterectomy and bilateral
      oophorectomy. METHODS: The study covers 1998 through 2002 and involves
      Surveillance, Epidemiology, and End Results Program; Behavior Risk Factor
      Surveillance System; and National Health Interview Survey data. Prevalence data
      were obtained by using survey and life-table methods. Four racial groups are
      considered: whites, blacks, American Indians/Alaska Natives, and Asians/Pacific
      Islanders. RESULTS: Risk correction significantly increased rates of corpus
      uterine cancer by 73.1% for whites, 93.0% for blacks, 86.3% for American
      Indians/Alaska Natives, and 41.0% for Asians/Pacific Islanders. Corresponding
      percentages among these racial groups for cervical cancer were 37.7%, 60.2%,
      45.6%, and 33.0%, and for ovarian cancer, 32.5%, 31.1%, 35.0%, and 23.6%,
      respectively. Risk correction had large influences on the comparison of rates
      among racial groups. For example, for uterine corpus cancer, Asians/Pacific
      Islanders had 32.9% lower rates than whites before correction, but 45.3% lower
      rates after correction. For cervical cancer, blacks had 27.6% higher rates than
      whites before correction, but 48.5% higher rates after correction; and for
      ovarian cancer, Asians/Pacific Islanders had 31.2% lower rates than whites before
      correction and 35.8% lower rates after correction. CONCLUSIONS: Corrected rates
      of corpus uteri, cervix uteri, and ovarian cancers have a large, but
      differential, impact on the racial groups considered.

PMID- 17027291
TI  - Regarding "selection and recall bias in a case-control study of lifetime alcohol
      intake and breast cancer risk".

PMID- 17027292
TI  - Cumulative socioeconomic status across the life course and subclinical
      atherosclerosis.
AB  - PURPOSE: The purpose of this study is to investigate the relationship between
      individual-level and neighborhood-level socioeconomic status (SES) across the
      life course and subclinical atherosclerosis. METHODS: Participants from the
      Atherosclerosis Risk in Communities Study (n=12,332) were queried about
      individual-level SES and residential addresses across the life course. Individual
      level measures were scored and summed to obtain a summary score (I-CumSES),
      whereas residential addresses were geocoded and linked to census data to obtain a
      summary neighborhood z score (N-CumSES) to evaluate the association of SES with
      intima-media thickness (IMT) and peripheral arterial disease (PAD). RESULTS: A 1
      SD lower I-CumSES was associated with greater mean IMT in each race-sex group and
      greater odds of PAD in white men (odds ratio [OR], 1.28; 95% confidence interval
      [CI], 0.99-1.64), white women (OR, 1.18; 95% CI, 1.02-1.36), and black women (OR,
      1.33; 95% CI, 1.00-1.76). Compared with the highest tertile of N-CumSES, the
      lowest tertile was associated with greater mean IMT among whites, but was not
      associated with PAD for whites or blacks. When I-CumSES and N-CumSES were
      considered simultaneously, associations remained for only I-CumSES and were
      attenuated after adjustment for cardiovascular disease (CVD) risk factors.
      CONCLUSIONS: Lower cumulative individual-level SES across the life course was
      associated with a greater burden of subclinical atherosclerosis, and this
      association was mediated in part by CVD risk factors.

PMID- 17027293
TI  - Suicide risk among Chernobyl cleanup workers in Estonia still increased: an
      updated cohort study.
AB  - PURPOSE: The aim of the study is to examine the mortality experience among
      Chernobyl cleanup workers. METHODS: A cohort study of 4786 men from Estonia who
      participated in the Chernobyl cleanup from 1986 to 1991 and were traced until
      December 31, 2002. Standardized mortality ratio (SMR) and adjusted mortality rate
      ratio (RR) derived through Poisson regression analysis were calculated. RESULTS:
      During follow-up, 550 deaths occurred, yielding an SMR of 1.01 (95% confidence
      interval [CI], 0.92-1.09). Increased risks were observed for suicide alone (SMR,
      1.32; 95% CI, 1.03-1.67) and suicide combined with undetermined injury (SMR,
      1.29; 95% CI, 1.03-1.60). One leukemia death occurred, and no thyroid cancer
      deaths were found. Elevated mortality also was observed for brain cancer (SMR,
      2.78; 95% CI, 1.02-6.05). The adjusted RR for suicide remained stable over the
      time passed since return from the Chernobyl area, showing RRs of 1.09 (95% CI,
      0.56-2.10) for 5 to 9 years and 1.00 (95% CI, 0.48-2.05) for 10 or more years
      compared with less than 5 years. CONCLUSIONS: During the 17 years after the
      accident, suicide risk in the cohort was greater than in the general male
      population. No elevated risk in overall mortality and radiation-related cancers
      was observed. The long-term nature of this elevated risk provides concrete
      evidence that psychological consequences represent the largest public health
      problem caused by the accident to date.

PMID- 17027295
TI  - Severe back pain among farmworker high school students from Starr County, Texas:
      baseline results.
AB  - PURPOSE: This cohort study is among the first to estimate the prevalence of and
      examine potential risk factors for severe back pain (resulting in medical care,
      4+ hours of time lost, or pain lasting 1+ weeks) among adolescent farmworkers.
      These youth often perform tasks requiring bent/stooped postures and heavy
      lifting. METHODS: Of 2536 students who participated (response rate across the
      three public high schools, 61.2% to 83.9%), 410 students were farmworkers
      (largely Hispanic and migrant). Students completed a self-administered Web-based
      survey including farm work/nonfarm work and back-pain items relating to a 9-month
      period. RESULTS: The prevalence of severe back pain was 15.7% among farmworkers
      and 12.4% among nonworkers. The prevalence increased to 19.1% among farm workers
      (n = 131) who also did nonfarm work. A multiple logistic regression for
      farmworkers showed that significantly increased adjusted odds ratios for severe
      back pain were female sex (4.59); prior accident/back injury (9.04); feeling
      tense, stressed, or anxious sometimes/often (4.11); lifting/carrying heavy
      objects not at work (2.98); current tobacco use (2.79); 6+ years involved in
      migrant farm work (5.02); working with/around knives (3.87); and working on corn
      crops (3.40). CONCLUSIONS: Areas for further research include ergonomic exposure
      assessments and examining the effects of doing farm work and nonfarm work
      simultaneously.

PMID- 17027294
TI  - Reliability of serum assays of iron status in postmenopausal women.
AB  - PURPOSE: The aim of the study is to determine the reliability during a 2-year
      period of several newly developed iron-related assays to assess their potential
      for use in prospective epidemiologic studies. METHODS: We assessed the temporal
      reliability of several iron-related assays by using three serum samples collected
      at yearly intervals from 50 postmenopausal participants in a large prospective
      study. RESULTS: We observed high reliability coefficients for ferritin (0.78; 95%
      confidence interval [CI], 0.67-0.86), soluble transferrin receptor (sTfR; 0.79;
      95% CI, 0.69-0.87), sTfR/ferritin ratio (0.74; 95% CI, 0.62-0.83), and hepcidin
      (0.89; 95% CI, 0.84-0.94). In a subset of 30 women, lower reliability was
      observed for serum iron (0.50; 95% CI, 0.29-0.70), unsaturated iron-binding
      capacity (0.55; 95% CI, 0.34-0.73), total iron-binding capacity (0.60; 95% CI,
      0.40-0.76), and serum transferrin saturation rate (0.44; 95% CI, 0.22-0.65). The
      reliability of anti-5-hydroxymethyl-2'-deoxyuridine autoantibody titers, a
      biomarker of oxidized DNA damage, one of the mechanisms by which iron is thought
      to impact disease risk, was very high (0.97, 95% CI, 0.5-0.99). CONCLUSIONS: Our
      results show that some newly developed iron-related assays could be useful tools
      to assess iron-disease associations in prospective cohorts that collect a single
      blood sample.

PMID- 17027296
TI  - Cross-sectional and prospective associations between passive smoking and
      respiratory symptoms at the workplace.
AB  - PURPOSE: The purpose of the study is to investigate the cross-sectional and
      prospective relation between workplace secondhand smoke (SHS) exposure and
      respiratory symptoms. METHODS: Cross-sectional data for workplace SHS exposure
      and respiratory symptoms were collected by using random digit dialing from 7336
      never-smoking Hong Kong workers 15 years or older in 1997 to 1998. In the 2000 to
      2001 follow-up, 2213 workers who remained never smoking, had the same SHS
      exposure status, worked at the same job for at least 2 years, and were not
      exposed to SHS at home at follow-up were included for prospective analysis.
      RESULTS: Cross-sectionally, SHS was associated significantly with frequent colds,
      cough and phlegm, throat problems, and the presence of any respiratory symptoms
      with adjusted odds ratios of 1.89 (95% confidence interval [CI], 1.66-2.15), 1.65
      (95% CI, 1.35-2.02), 1.88 (95% CI, 1.63-2.15), and 1.96 (95% CI, 1.75-2.20) at
      baseline, each having significant linear associations with duration of exposure.
      SHS was not associated with rhinitis. Prospectively, consistent SHS exposure
      increased the risk for cough and phlegm and any respiratory symptoms by 48% (12%
      to 97%) and 54% (13% to 109%), respectively. CONCLUSIONS: This first non-Western
      population-based prospective study shows that workplace SHS exposure is
      associated significantly with frequent respiratory symptoms, both cross
      sectionally and prospectively, thus providing strong evidence that the
      association is causal.

PMID- 17027297
TI  - First- and third-person approaches in implicit learning research.
AB  - How do we find out whether someone is conscious of some information or not? A
      simple answer is "We just ask them"! However, things are not so simple. Here, we
      review recent developments in the use of subjective and objective methods in
      implicit learning research and discuss the highly complex methodological problems
      that their use raises in the domain.

PMID- 17027298
TI  - CD8alpha+ dendritic cells are required for efficient entry of Listeria
      monocytogenes into the spleen.
AB  - In addition to their bridging function between innate and adaptive immunity,
      dendritic cells (DCs) may also contribute to primary resistance against
      infection. Here we analyzed the role of DCs during infection with Listeria
      monocytogenes by performing systemic in vivo depletion of these cells. We showed
      that CD8alpha(+) DCs were crucial for L. monocytogenes spreading and
      proliferation in the spleen. Efficient and rapid uptake of L. monocytogenes by
      CD8alpha(+) DCs required the small GTPase Rac1 and is a general characteristic of
      this DC subpopulation in filtering particles out of the blood. Thus, CD8alpha(+)
      DCs appear to play an important role for efficient bacterial entry into the
      spleen, which is of relevance for subsequent immune responses.

PMID- 17027299
TI  - Innate immune activation and CD4+ T cell priming during respiratory fungal
      infection.
AB  - Aspergillus fumigatus is a mold that causes a spectrum of diseases, including
      lethal lung infections in immunocompromised humans and allergic asthma in atopic
      individuals. T helper 1 (Th1) CD4(+) T cells protect against invasive A.
      fumigatus infections whereas Th2 CD4(+) T cells exacerbate asthma upon inhalation
      of A. fumigatus spores. Herein, we demonstrate that A. fumigatus-specific T cells
      were rapidly primed in lymph nodes draining the lung and fully differentiated
      into interferon-gamma (IFN-gamma)-producing Th1 CD4(+) T cells upon arrival in
      the airways. T-bet induction in A. fumigatus-specific CD4(+) T cells was enhanced
      by MyD88-mediated signals in draining lymph nodes, but T cell proliferation,
      trafficking, and Th1 differentiation in the airways were Toll-like receptor (TLR)
      and MyD88 independent. Our studies demonstrate that CD4(+) T cell differentiation
      during respiratory fungal infection occurs incrementally, with TLR-mediated
      signals in the lymph node enhancing the potential for IFN-gamma production
      whereas MyD88-independent signals promote Th1 differentiation in the lung.

PMID- 17027301
TI  - Letter to the editor re: "Preoperative radiological assessment for vascular
      access". Eur J Vasc Endovasc Surg 2006;31:64-69.

PMID- 17027300
TI  - A role for the endoplasmic reticulum protein retrotranslocation machinery during
      crosspresentation by dendritic cells.
AB  - Crosspresentation of exogenous antigens (Ags) to CD8(+) T cells by dendritic
      cells generally requires their entry into the cytosol. Here we show that both
      soluble and phagocytosed extracellular Ags accessed the cytosol via molecular
      components required for endoplasmic reticulum (ER)-associated degradation (ERAD).
      Exogenous Pseudomonas aeruginosa Exotoxin A, which inhibits protein translocation
      from the ER to the cytosol, abrogated crosspresentation. Exotoxin A also
      prevented the transporter associated with antigen processing (TAP) inhibitor,
      ICP47, from entering the cytosol and blocking TAP-mediated peptide transport. In
      an in vitro model of retrotranslocation, the AAA ATPase p97, an enzyme critical
      for ERAD, was the only cytosolic cofactor required for protein export from
      isolated phagosomes. Functional p97 was also required for crosspresentation but
      not conventional presentation. Thus, crosspresentation appears to result from an
      adaptation of the retrotranslocation mechanisms involved in the degradation of
      misfolded ER proteins.

PMID- 17027302
TI  - Medical optimisation can reduce morbidity and mortality associated with elective
      aortic aneurysm repair.
AB  - OBJECTIVES: Patients with aortic aneurysms have significant comorbidities which
      influence outcome. Our practice includes comprehensive assessment to identify
      comorbidities, allowing subsequent medical optimisation prior to aneurysm repair.
      The aim of this study was to assess this process and to identify any factors
      predictive of outcome. DESIGN: Prospective observational study. MATERIALS:
      Medical case notes of 200 patients referred with aortic pathology. METHODS: Data
      analysed included preoperative, perioperative and postoperative factors. Multiple
      logistic regression analysis was performed to identify predictors of outcome.
      RESULTS: Following assessment 17 patients (8.5%) were found to be unfit for
      intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group
      assessment uncovered previously undiagnosed cardiac, respiratory and renal
      comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic
      regression analysis indicated that optimisation by a renal physician reduced post
      operative renal impairment (OR 0.12, 95% CI 0.03-0.45, P=0.002) while
      optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI
      0.05-0.99, P=0.049). An abnormal echocardiogram was associated with pneumonia (OR
      6.9, 95% CI 1.6-29, P=0.01) and death (OR 7.9, 95% CI 1.15-54, P=0.036).
      CONCLUSION: Pre-operative assessment identifies previously undiagnosed
      comorbidity in a significant proportion of patients. Subsequent medical
      optimisation may reduce post-operative morbidity and mortality.

PMID- 17027303
TI  - Getting a grip on strangles.

PMID- 17027304
TI  - Home truths about scientific truth.

PMID- 17027305
TI  - Anisotropic diffusion of metabolites in peripheral nerve using diffusion weighted
      magnetic resonance spectroscopy at ultra-high field.
AB  - Although the diffusivity and anisotropy of water has been investigated thoroughly
      in ordered axonal systems (i.e., nervous tissue), there have been very few
      studies on the directional dependence of diffusion of metabolites. In this study,
      the mean apparent diffusion coefficient (Trace/3 ADC) and fractional anisotropy
      (FA) values of the intracellular metabolites N-acetyl aspartate (NAA), creatine
      and phosphocreatine (tCr), choline (Cho), taurine (Tau), and glutamate and
      glutamine (Glx) were measured parallel and perpendicular to the length of excised
      frog sciatic nerve using a water suppressed, diffusion-weighted, spin-echo pulse
      sequence at 18.8T. The degree of anisotropy (FA) of NAA (0.41+/-0.09) was
      determined to be less than tCr (0.59+/-0.07) and Cho (0.61+/-0.11), which is
      consistent with previously reported human studies of white matter. In contrast,
      Glx diffusion was found to be almost isotropic with an FA value of 0.20+/-0.06.
      The differences of FA between the metabolites is most likely due to their
      differing micro-environments and could be beneficial as an indicator of
      compartment specific changes with disease, information not readily available with
      water diffusion.

PMID- 17027306
TI  - A field-sweep/field-lock system for superconducting magnets--Application to high
      field EPR.
AB  - We describe a field-lock/field-sweep system for the use in superconducting
      magnets. The system is based on a commercially available field mapping unit and a
      custom designed broad-band 1H NMR probe. The NMR signal of a small water sample
      is used in a feedback loop to set and control the magnetic field to high
      accuracy. The current instrumental configuration allows field sweeps of +/-0.4 T
      and a resolution of up to 10(-5) T (0.1 G) and the performance of the system is
      demonstrated in a high-field electron paramagnetic resonance (EPR) application.
      The system should also be of utility in other experiments requiring precise and
      reproducible sweeps of the magnetic field such as DNP, ENDOR or PELDOR.

PMID- 17027307
TI  - HMQC and refocused-INEPT experiments involving half-integer quadrupolar nuclei in
      solids.
AB  - Hetero-nuclear coherence transfers in HMQC and refocused-INEPT experiments
      involving half-integer quadrupolar nuclei in solids are analyzed. 1D and 2D
      schemes are considered under MAS for the general case of multi-spin systems SI(n)
      (n4), where S is an observed nucleus. These results are also discussed in the
      context of high-resolution schemes featuring MQMAS or STMAS. The theoretical
      predictions are verified experimentally in a series of 1D and 2D experiments
      performed at 9.4 and 18.8T.

PMID- 17027308
TI  - Three-dimensional through-bond homonuclear-heteronuclear correlation experiments
      for quadrupolar nuclei in solid-state NMR applied to (27)Al-O-(31)P-O-(27)Al
      networks.
AB  - We present here the first 3D homonuclear/heteronuclear correlation experiment
      applied to quadrupolar nuclei and making use of the sole scalar J-coupling. This
      experiment, based on the 2D-Homonuclear-Heteronuclear Single Quantum Correlation
      (H-HSQC) experiment, uses a relayed transfer from the (27)Al central transition
      to neighbouring (31)P spins and to the central transition of a second (27)Al. It
      confirms the correlation map characterizing the two (27)Al and the (31)P NMR
      signatures of (27)Al-O-(31)P-O-(27)Al chemically bonded molecular motifs.

PMID- 17027309
TI  - Towards understanding the mechanism of action of the multidrug resistance-linked
      half-ABC transporter ABCG2: a molecular modeling study.
AB  - The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC
      transporters with potential clinical importance as a mediator of multidrug
      resistance. We carried out a homology and knowledge-based, and mutationally
      improved molecular modeling study to establish a much needed structural framework
      for the protein, which could serve as guidance for further genetic, biochemical,
      and structural analyses. Based on homology with known structures of both full
      length and nucleotide-binding domains (NBD) of ABC transporters and structural
      knowledge of integral membrane proteins, an initial model of ABCG2 was
      established. Subsequent refinement to conform to the lipophilic index
      distributions in the transmembrane domain (TMD) and to the results of site
      directed mutagenesis experiments led to an improved model. The complete ABCG2
      model consists of two identical subunits facing each other in a closed
      conformation. The dimeric interface in the nucleotide-binding domain (NBD)
      involves a characteristic nucleotide sandwich and the interface in the TMD
      consists of the TM helices 1-3 of one subunit and the helices 5 and 6 of the
      other. The interface between the NBD and the TMD is bridged by the conserved
      structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the
      terminal beta-strand (S6) of the central beta-sheet in the NBD. The apparent
      flexibility of the ICD1 may play a role in transmitting conformational changes
      from the NBD to the TMD or from the TMD to the NBD.

PMID- 17027310
TI  - Genetic mutation profile of isovaleric acidemia patients in Taiwan.
AB  - Isovaleric acidemia (IVA), a rare recessive autosomal disorder, is caused by
      isovaleryl-CoA dehydrogenase (IVD) deficiency. IVA may present with symptoms
      during the acute stage of severe metabolic acidosis, ketosis, vomiting, and
      altered mental status. With the help of newborn screening (NBS) by tandem mass
      spectrometry (MS/MS), IVA can now be diagnosed presymptomatically. According to
      statistic data, the incidence of IVA in Taiwan was about 1/365,000. In this
      study, six IVA patients from five families were investigated and followed-up
      clinically. As for the timing, two patients were found before MS technique
      introduced to Taiwan, the others were identified after MS/MS applied to NBS. The
      blood level of C5-carnitine in our patients was 7.43-18.96 microM (with upper
      limit in our laboratory <0.51 microM) and all of their urines contained raised
      amounts of 3-hydroxyisovaleric acid and isovalerylglycine. Molecular analysis of
      their IVD gene revealed six mutation profiles, among which the 149G-->A
      (Arg21His) and 1174 C-->T (Arg363Cys) mutations have been reported previously,
      while the other four mutations, 386A-->G (His100Arg), 347C-->T (Ser87Phe), 1007G-
      >A (Cys307Tyr) and 1199A-->G (Tyr371Cys), were first reported. Specially, we
      found 1199A-->G (Tyr371Cys) mutated was a common recurring missense mutation in
      our population (4 in 10 mutant alleles).

PMID- 17027311
TI  - Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian
      mutations with novel mutations.
AB  - Inherited mutations of a purine salvage enzyme, hypoxanthine guanine
      phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome
      or HPRT-related gout. We have identified a number of HPRT mutations in Asian
      patients manifesting different clinical phenotypes, by analyzing all nine exons
      of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the
      PCR technique coupled with direct sequencing. In this study, we update the
      spectrum of mutations with nine novel mutations. Two missense mutations (T124P
      and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a
      patient having a severe partial deficiency of HPRT with neurological dysfunction
      (HRND: HPRT-related neurological dysfunction), a single nucleotide substitution
      (27+5G > A) causing a splicing error was found in intron 1. The mutation resulted
      in a remarkably decreased level of normal mRNA, and production of an abnormal
      mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift
      of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found
      two 3-bp deletions responsible for single amino acid deletions (V8del and
      Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an
      insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4
      to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42
      HPRT1 mutations have been identified among 47 Asian families with deficiency of
      HPRT.

PMID- 17027312
TI  - [Valorisation of high technology radiotherapy in Europe].
AB  - In order to support adoption and dissemination into clinical practice of
      innovative treatment strategies, being almost by definition more expensive than
      the corresponding standard treatments, an appropriate reimbursement is a
      prerequisite. This article describes different possible financing systems in the
      context of technological advances in radiation oncology and analyses if and how
      the reimbursement issue has been tackled in European radiotherapy centres.

PMID- 17027313
TI  - Sexual differences in Turkish dentition.
AB  - Sexual variation in the human skeleton and dentition is of great concern for both
      anthropologists and odontologists. Assessment of variation in dental size gives a
      clue about the behavior of a population, and also differences between the sexes.
      This study deals with sexual differences in a Turkish sample of individuals
      ranging in age from 20 to 29 years. The sample is composed of 28 buccolingual
      (BL) and mesiodistal (MD) dimensions of upper and lower dentition (I1 through
      M2). Dental casts of 50 males and 50 females were analyzed using discriminant
      function statistics. The results indicated that 8 of the upper and 7 of the lower
      dimensions were significantly greater in males. Many of the differences were
      located in the anterior teeth of both jaws. In a stepwise function applied to
      both arches, the lower and upper canine BL, lower canine and P1 MD, and lower I2
      BL were used as the most discriminating variables. When the front teeth (i.e.,
      I1, I2, and C) are used in separate functions, only the canine BL of the lower
      jaw and I2 and C BL of the upper jaw were found to have the discriminating
      variables. Classification accuracy was 81% for the total sample, 76% for upper
      front and 81% for lower front teeth. In conclusion, dentition in Turkish people
      seems to be less sexually dimorphic than the populations with which they were
      compared (Jordanians, Swedish and South Africans) as was determined by the
      percent of accuracy obtained. In comparison with other populations, as
      anticipated, Turkish dental size is closest to the Jordanian sample and farthest
      from the South African whites.

PMID- 17027314
TI  - Application of salicylic acid dosimetry to evaluate hydrodynamic cavitation as an
      advanced oxidation process.
AB  - The generation of OH* radicals inside hydrodynamic cavitation bubbles was
      monitored using a salicylic acid dosimeter. The reaction of this scavenger with
      OH* produces 2,5-dihydroxybenzoic acid (2,5-DHB) and, to a lesser degree, 2,3
      DHB. The former, is a specific reaction product that can be determined with a
      very high sensitivity using HPLC-IF. This method has been applied to study the
      influence of the flow-rate and the solution pH for a given cavitation chamber
      geometry. The salicylic dosimetry has proven especially suitable for the
      characteristic time scales of hydrodynamic cavitation (higher than those of
      ultrasonic cavitation), which usually gives rise to recombination of radicals
      before they can reach the liquid-phase. Working at low pH the hydrophobic
      salicylic acid migrates to the gas-liquid interface and reacts with the OH*
      radicals, increasing the trapping efficiency of the dosimeter. Hydrodynamic
      cavitation works as a very low frequency sonochemical reactor, and therefore its
      potential as an Advanced Oxidation Process might be limited to reactions at the
      gas-liquid interface and inner bubble (i.e. with volatiles and/or hydrophobic
      substances).

PMID- 17027315
TI  - Development of a novel articulator that reproduced jaw movement with six-degree
      of-freedom.
AB  - A novel robotic articulator that reproduced a six-degree-of-freedom jaw movement
      was developed and tested. A precise six-axis micro-positioning stage was employed
      for this articulator. A high-resolution jaw-tracking device measured the
      functional jaw movement of the patient and a six-axis micro-positioning stage
      reproduced recorded jaw movement data. A full veneer crown restoration was
      fabricated with this articulator system. A working cast was mounted on the
      positioning stage of the articulator. An occlusal table with soft wax was
      attached on the cast tooth die, and the jaw movements were reproduced to create a
      functionally generated path on the occlusal table. The finished occlusal record
      was used to obtain the wax pattern for the crown. In this subject, no intra-oral
      occlusal adjustment was necessary for setting the finished full veneer crown.
      Since this articulator could perform a precise reproduction of the dynamic jaw
      motion during the functional jaw movement, this system has potential to improve
      accuracy of the prosthetic teeth occlusion.

PMID- 17027316
TI  - The development and practice of forensic podiatry.
AB  - Forensic podiatry is a small, but potentially useful specialty using clinical
      podiatric knowledge for the purpose of person identification. The practice of
      forensic podiatry began in the early 1970s in Canada and the UK, although
      supportive research commenced later in the 1990s. Techniques of forensic podiatry
      include identification from podiatry records, the human footprint, footwear, and
      the analysis of gait forms captured on Closed Circuit Television Cameras. The
      most valuable techniques relate to the comparison of the foot impressions inside
      shoes. Tools to describe, measure and compare foot impressions with footwear wear
      marks have been developed through research with potential for further
      development. The role of forensic podiatrists is of particular value when dealing
      with variable factors relating to the functioning and the shod foot. Case studies
      demonstrate the approach of podiatrists, in footwear identification, when
      comparing exemplar with questioned foot impressions. Forensic podiatry practice
      should be approached cautiously and it is essential for podiatrists undertaking
      this type of work to understand the context within which the process of person
      identification takes place.

PMID- 17027317
TI  - Agricultural and horticultural pesticides fatal poisoning; the Jordanian
      experience 1999-2002.
AB  - A prospective autopsy study addressing fatal poisoning with agricultural and
      horticultural pesticides was undertaken in Jordan over a 4 year period. A total
      number of 140 deaths occurred during 1999-2002. The mean fatality rate was 0.68
      case per 100,000 population and the age range was 2-55 years; mean 28.3 years
      with male to female ratio 1.03. The largest number of cases occurred in those 20
      29 years (n=69, 49.3%) followed by the age group 30-39 years (n=34, 24.3%) and 40
      49 years (n=17, 12.1%). Less than 3.0% of the total fatal poisoning was noticed
      in both children younger than 9 years of age and those in the age group 50-59
      years, with no fatal poisoning in adults at the age 60 years and above. At least
      64.3% of all pesticide fatalities were due to suicide with male: female ratio
      (1.37:1). Accidental and homicide poisoning resulted in 24.3% and 7.9% of the
      total fatalities, respectively; however, only five cases 3.6% of fatal poisoning
      were due to unknown pesticides. The main pesticide used was carbamates with 110
      cases 78.6% followed by organophosphorus 23 cases 16.4%. The study showed that
      the present legislation on pesticides availability in Jordan failed to reduce the
      number of fatal pesticides poisoning since the number of fatal pesticides
      poisoning was increased from 25.3 to 35 cases per year over a 20 years period.
      Enforcement of a new legislation addressing the availability of agricultural and
      horticultural pesticides for self-harm, especially carbamates and
      organophosphorus, is the most important strategy in the long term to prevent
      fatal pesticides poisoning in Jordan.

PMID- 17027318
TI  - Fatal asphyxia by a thyroglossal duct cyst in an adult.
AB  - Thyroglossal duct cysts arise from remnants of embryonic thyroglossal duct that
      connects the foramen cecum at the base of the tongue to the thyroid gland. The
      remnants enlarge secondary to secretions from the epithelial lining. Usually,
      thyroglossal cysts present as non-tender masses. However, they may also become
      infected, produce fistulas or give hoarseness and dysphagia. Rarely, especially
      if the mass is located at the base of the tongue, airway obstruction and dyspnea
      can ensue. This unusual presentation has been mainly seen in very young children
      and has caused death in about half of these cases. Nevertheless, in the adult
      population, very few cases of airway obstruction by thyroglossal duct cysts have
      been reported, only one being fatal. We present the case of a 55-year-old man who
      died from fatal asphyxia caused by a thyroglossal cyst.

PMID- 17027319
TI  - Delayed deaths after vascular traumatism: two cases.
AB  - During expert testimony in court, forensic pathologists are often asked to
      estimate the length of survival following fatal injuries. Though it is impossible
      to be precise, fatal vascular trauma survival times are generally considered
      short. We here report two unusual cases of delayed deaths, one following
      homicidal stabbing of the heart and the other by suicidal cutting of the neck. In
      those two cases, investigation clearly provided evidence of prolonged survival:
      slightly more than 2h for the first case and about 8h for the second. Relevant
      literature is revised and physiopathological hypotheses are discussed.

PMID- 17027320
TI  - Macrophage activation syndrome: an autopsy case of sudden death.
AB  - In a context of viral gastroenteritis, we report an unusual case of sudden death
      in an 8-year-old child. The only macroscopic abnormality observed in the autopsy
      was a diffuse mesenteric adenitis. Organ samples were taken for histopathological
      examination and a diffuse lymphocytic infiltration was observed. A sinusoidal
      histiocytic hyperplasia was found in the lymph nodes. Microscopic examination of
      the lungs and the lymph nodes revealed haemophagocytic lesions (lymphocytes
      within the cytoplasm of histiocytic macrophages). Immunohistochemical studies
      demonstrated that the histiocytes were CD68+ PS100- CD1A-. Following this
      microscopic examination macrophage activation or haemophagocytic syndrome was
      diagnosed. The syndrome is a distinct clinical entity characterised by fever,
      pancytopaenia, splenomegaly, and haemophagocytosis in the bone marrow, liver and
      lymph nodes. It is a clinical entity that is very difficult to diagnose due to
      the lack of specific clinical signs. It is generally a complication of an
      infectious process, an aggravation of an auto-immune disease or a complication of
      a neoplastic process. The physiopathology involves a disregulation of T
      lymphocytes and particularly T helper lymphocytes. To make this diagnosis the
      anatomopathological examination must be performed by an experienced practitioner.
      The presence of a lymphocyte infiltrate of macrophagic histiocytes in myeloid
      organs and especially positive CD68+ immune markers are the anatomopathological
      proofs of diagnosis. The autopsy examination must be carefully performed and
      include systematic sample harvesting for anatomopathological examination. The
      results of all these examinations taken together allow the diagnosis of
      haemophagocytic syndrome to be finally made.

PMID- 17027321
TI  - Children and adolescents victimized by sexual abuse in the city of Rio de
      Janeiro: an appraisal of cases.
AB  - Physical and/or sexual abuse, negligence, and psychological abuse against
      children and adolescents, constitute a socially important syndrome, demanding
      preventive public policies and rules for its eradication. Sexual abuse, as a
      troublesome occurrence, or even its mere presumption, does not regularly undergo
      official notification. We have examined legal investigative registers at the
      Instituto Medico-Legal do Rio de Janeiro - Sede set up from January to March
      2000, including women, children and adolescents, with medico-legal histories
      suggestive of sexual assault. From a sample of 1419 cases, we selected those
      involving vaginal coitus or other libidinous practices, with an upper age limit
      of 17 years, reducing our sample to 44 subjects. 84.09% of the assaults occurred
      between ages 0 and 14 years. In 62.36% of the studied cases there was no mention
      about perpetrators. Material for laboratory researches had not been collected in
      84.09% of the cases. There is any lesions in 70.45% of the sample.

PMID- 17027322
TI  - Sudden cardiac death associates with a large right atrium thrombus in a late
      survivor of heart transplantation.
AB  - A fatal circulatory collapse developed acutely in a patient six years after
      orthotopic heart transplantation. Autopsy revealed a large, fresh thrombus inside
      the right atrium which obstructed the orifice of the vena cava completely. The
      grafted coronary artery and pulmonary vessels were patent. There was no rejection
      or acute infarct in myocardium. Mildly immature organization was seen on the
      thrombus-adhered wall. Four chamber enlargement and a rapid decline of right
      ventricular hypokinesia were detected shortly before death although he did not
      show active cardiopulmonary symptom. Intracardiac thrombus formation is rather
      uncommon in late survivor. A synergic effect of atrial turbulence and ventricular
      hypokinesia in the right heart, superimposed by tissue organization, was proposed
      for thrombus formation. An empty cardiac output was favored for his mortality.
      These findings provide a strong evidence to suggest anticoagulation in case of
      complicated or highly risk of embolization such as turbulence or hypokinesia
      despite of an absence of active cardiopulmonary symptom.

PMID- 17027323
TI  - Cerebellar-pulmonary embolism, cause of death in the newborn.
AB  - A 28-year-old woman delivered twin girls. The first twin was delivered without
      any difficulty. The head of the second twin failed to descend with pushing. A
      special kind of obstetrical forceps, Thierry's spatulas, were used to extract the
      second twin in the occipito-posterior vertex position. She was declared dead
      after recording Apgar scores of 0 and 0 and after 35 min of resuscitation. An
      autopsy was performed for medico-legal reasons. Macroscopic examination of the
      brain showed a small area of leptomeningeal haemorrhage in the left sylvian fossa
      and the base of the brain. Histopathological studies demonstrated cerebellar
      tissue emboli in meningeal and pulmonary arteries. Excessive pressure on the
      suboccipital region during delivery can cause traumatic separation of the
      occipital chondral junctions, which may lead to separation of the occipital
      squama from lateral parts of the occipital bones. The inferior part of the
      occipital squama is displaced forward and upward into the posterior fossa. This
      produces tearing of the duramater and occipital sinuses leading to leptomeningeal
      haemorrhage in the posterior cranial fossa, often associated with cerebellar
      lesions. Major stretching and tearing of the posterior aspect of tentorium
      cerebelli in contact with the sinuses and the cerebellar cortex may also occur,
      inducing slight movement of the occipital bones and subsequent emboli. This case
      study is that of a newborn death due to pulmonary cerebellar tissue embolism
      occurring during delivery with Thierry's forceps, which are considered less
      traumatic to the foetal cranium. A review of the literature identified 17 other
      published cases. In difficult deliveries this pathology should sought carefully.
      Brain, lung and placenta tissue sections must be studied.

PMID- 17027324
TI  - New views of S-RNase-based self-incompatibility.
AB  - S-RNase-based self-incompatibility (SI) is the most widespread form of
      genetically controlled mate selection in plants. S-RNase controls pollination
      specificity in the pistil, while the newly discovered SLF/SFB controls
      pollination specificity in the pollen. A widely discussed model suggests that
      compatibility is explained by ubiquitylation and degradation of nonself-S-RNase
      and that, conversely, incompatibility is caused by failure to degrade self-S
      RNase. This model is consistent with the long-standing view that S-RNase
      inhibition is central to SI. Recent results show, however, that S-RNase is
      compartmentalized in pollen tubes and, significantly, that compatibility might
      not require SLF/SFB. S-RNase compartmentalization and dislocation into the pollen
      tube cytoplasm might be similar to the trafficking of other cytotoxins such as
      ricin.

PMID- 17027325
TI  - Mutagenic and carcinogenic potential of a textile azo dye processing plant
      effluent that impacts a drinking water source.
AB  - Recently a textile azo dye processing plant effluent was identified as one of the
      sources of mutagenic activity detected in the Cristais River, a drinking water
      source in Brazil [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D.
      Claxton, Investigating the sources of the mutagenic activity found in a river
      using the Salmonella assay and different water extraction procedures, Chemosphere
      54 (2004) 1589-1597]. Besides presenting high mutagenic activity in the
      Salmonella/microsome assay, the mutagenic nitro-aminoazobenzenes dyes CI Disperse
      Blue 373, CI Disperse Violet 93, and CI Disperse Orange 37 [G.A. Umbuzeiro, H.S.
      Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The
      contribution of azo dyes in the mutagenic activity of the Cristais river,
      Chemosphere 60 (2005) 55-64] as well as benzidine, a known carcinogenic compound
      [T.M. Mazzo, A.A. Saczk, G.A. Umbuzeiro, M.V.B. Zanoni, Analysis of aromatic
      amines in surface waters receiving wastewater from textile industry by liquid
      chromatographic with eletrochemical detection, Anal. Lett., in press] were found
      in this effluent. After approximately 6 km from the discharge of this effluent, a
      drinking water treatment plant treats and distributes the water to a population
      of approximate 60,000. As shown previously, the mutagens in the DWTP intake water
      are not completely removed by the treatment. The water used for human consumption
      presented mutagenic activity related to nitro-aromatics and aromatic amines
      compounds probably derived from the cited textile processing plant effluent
      discharge [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton,
      Investigating the sources of the mutagenic activity found in a river using the
      Salmonella assay and different water extraction procedures, Chemosphere 54 (2004)
      1589-1597; G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T.
      Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of
      the Cristais river, Chemosphere 60 (2005) 55-64]. Therefore, it is important to
      evaluate the possible risks involved in the human consumption of this
      contaminated water. With that objective, one sample of the cited industrial
      effluent was tested for carcinogenicity in the aberrant crypt foci medium-term
      assay in colon of Wistar rats. The rats received the effluent in natura through
      drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity
      was also confirmed in the Salmonella/microsome assay with the strains TA98 and
      YG1041. There was an increased number of preneoplastic lesions in the colon of
      rats exposed to concentrations of 1% and 10% of the effluent, and a positive
      response for both Salmonella strains tested. These results indicate that the
      discharge of the effluent should be avoided in waters used for human consumption
      and show the sensitivity of the ACF crypt foci assay as an important tool to
      evaluate the carcinogenic potential of environmental complex mixtures.

PMID- 17027326
TI  - Identification of the rosasite group minerals--an application of near infrared
      spectroscopy.
AB  - The ability of near infrared reflectance spectroscopy to classify the rosasite
      group minerals from spectral characteristics is demonstrated. NIR spectroscopy
      can be regarded as an alternative tool for structure analysis. The spectra show
      that rosasite group minerals with different cations can be distinguished. Ni2+ in
      nullaginite [Ni2(CO3)(OH)2] is conspicuous through a single broad band absorption
      feature at 8525 cm-1, extended from 11,000 to 7000 cm-1. The effect of Ni on Cu
      is seen in the spectrum of glaukosphaerite [(Cu, Ni)2(CO3)(OH)2] both by a red
      shift of the spectrum and reduction in intensity of bands with variable positions
      of band maxima for Cu2+ at 6995 cm-1 and Ni2+ at 7865 cm-1. The spectrum of
      rosasite [(Cu, Zn)2(CO)3(OH)2] is characterised by Cu2+ band at 7535 cm-1.
      Kolwezite [(Cu, Co)2(CO)3(OH)2] is a spectral mixture of Cu and Co but optically
      separated by Co2+ and Cu2+ peaks at 8385 and 7520 cm-1. Vibrational spectra of
      carbonates show a number of bands in the 7000-4000 cm-1 region attributable to
      overtones, combination of OH stretching and deformation modes. They appear to be
      uniform in nature since the structure of rosasite group minerals is identical.
      The complexity of these features varies between samples because of the variation
      in composition and hence is useful for discriminating different hydrous
      carbonates.

PMID- 17027327
TI  - Fluorescence properties of Nd3+-doped tellurite glasses.
AB  - The compositional and concentration dependence of luminescence of the (4)F(3/2)-
      >(4)I(J) (J=13/2, 11/2 and 9/2) transitions in four Nd(3+)-doped tellurite based
      glasses has been studied. The free-ion energy levels obtained for
      60TeO(2)+39ZnO(2)+1.0Nd(2)O(3) (TZN10) glass have been analysed using the free
      ion Hamiltonian model and compared with similar results obtained for Nd(3+):glass
      systems. The absorption spectrum of TZN10 glass has been analysed using the Judd
      Ofelt theory. Relatively longer decay rates have been obtained for Nd(3+)-doped
      phosphotellurite glasses. The emission characteristics of the (4)F(3/2)-
      >(4)I(11/2) transition, of the Nd(3+):TZN10 glass, are found to be comparable to
      those obtained for Nd(3+):phosphate laser glasses. The non-exponential shape of
      the emission decay curves for the (4)F(3/2)-->(4)I(11/2) transition is attributed
      to the presence of energy transfer processes between the Nd(3+) ions.

PMID- 17027328
TI  - Promoter analysis of the murine squalene epoxidase gene. Identification of a 205
      bp homing region regulated by both SREBP'S and NF-Y.
AB  - Squalene epoxidase (SE) is one of the most highly regulated enzymes of the
      cholesterol biosynthesis pathway. Here we identify the molecular basis for SREBP
      2 synergy with NF-Y as the prime regulator of SE gene transcription. As expected
      cholesterol markedly suppressed transcriptional activity, while SREBP-1a, -1c and
      -2 activated it. Knock down of SREBP-2 mRNA resulted in an 85% reduction in SE
      expression. Interspecies comparison of SE promoter sequences identified two
      conserved putative NF-Y sites that were found to be important for maximal SREBP
      dependent gene activation and one novel conserved sterol response element (SRE).
      Altogether three novel SREs were identified within a 205 bp region of the SE
      promoter. Each of the SREs was capable of binding SREBP-2 but mutation of all
      three, singly or in combination, did not completely eliminate the SREBP response.
      Our results demonstrate the critical dependence of this 205 bp region for sterol
      dependent regulation of SE and uncover a possible framework for SREBP-promoter
      interaction, including a potent synergy with NF-Y that may be of principal
      importance.

PMID- 17027329
TI  - Prolonged effect of single carnitine administration on fasted carnitine-deficient
      JVS mice regarding their locomotor activity and energy expenditure.
AB  - Carnitine is an essential cofactor for the oxidation of fatty acid in the
      mitochondria and an efficient therapeutics for primary carnitine deficiency. We
      herein analyzed the prolonged effects of carnitine on the reduced locomotor
      activity and energy metabolism of fasted carnitine-deficient juvenile visceral
      steatosis (jvs(-/-)) mice. We found that a single carnitine administration to 24
      h fasted jvs(-/-) mice in the morning increased both the locomotor activity and
      oxygen consumption at night not only on the same day, but also on the next day,
      when the carnitine levels in the blood and tissues were already as low as at the
      original carnitine-deficient state. We also found that fat utilization for energy
      production significantly increased under fasting even in jvs(-/-) mice and was
      stimulated in the carnitine-administrated fasted jvs(-/-) mice at night, in
      comparison to that observed in the saline-administered jvs(-/-) mice, at least
      for 2 days even under the low plasma and tissue carnitine levels. These results
      suggest that the low tissue carnitine levels are therefore not the sole rate
      limiting factor of general fatty acid oxidation in carnitine-deficient jvs(-/-)
      mice.

PMID- 17027330
TI  - Prevalence and prognostic significance of atrial fibrillation in outpatients with
      heart failure due to left ventricular systolic dysfunction.
AB  - INTRODUCTION: Atrial fibrillation (AF) is common in patients with heart failure
      (HF) due to left ventricular systolic dysfunction (LVSD), with conflicting
      prognostic data. The aim of our study was to assess the prevalence and incidence
      of AF in patients with HF and to determine the prognostic impact of baseline AF
      and the development of new onset AF. METHODS AND RESULTS: We included 1019
      outpatients with HF due to LVSD; follow-up time ranged from 3 to 64 months. At
      baseline 26.4% of patients had AF. Of the 284 patients with a follow-up ECG and
      baseline SR, 18.7% developed new onset AF. Patients with AF were older (p<0.001),
      more often male (p=0.04), and more likely to have a history of stroke (p=0.03),
      but were less likely to have IHD (p<0.001). Baseline rhythm was independent of
      LVEF and NYHA-class. Baseline AF was associated with increased all-cause
      mortality (HR 1.38; CI 1.07-1.78, p=0.01) and all-cause mortality/hospitalisation
      (HR 1.43; CI 1.22-1.68, p<0.001). When adjusted for baseline covariates, baseline
      AF was independently associated with an increased risk of experiencing the
      combined endpoint (HR 1.29; CI 1.05-1.58; p=0.02), but did not predict all-cause
      mortality. By multivariable analyses, new-onset AF was associated with increased
      risk of all-cause mortality/hospitalisation (HR 1.45; CI 1.05-2.00; p=0.02).
      CONCLUSION: In outpatients with HF due to LVSD, AF is a common co-morbidity,
      which adversely affects morbidity and mortality outcomes.

PMID- 17027331
TI  - Pressure tracings in obstructive Tako-Tsubo cardiomyopathy.
AB  - A 70-year-old female experienced severe anxiety due to an incident with a
      stranger when she was home alone at night. Immediately after the event, she had
      an oppressive chest sensation; 16 h later she was admitted to hospital. Left
      ventriculography showed akinesia of the mid-to-distal portion and hyperkinesia of
      the basal portion of the left ventricular chamber. However, coronary angiography
      showed no significant coronary artery disease. We diagnosed her as having Tako
      Tsubo cardiomyopathy. Subsequently, left ventricular and central aortic pressures
      were recorded simultaneously. Initial recording showed a peak systolic gradient
      of 60 mm Hg. On the first sinus beat after a premature ventricular contraction,
      the peak systolic gradient increased to 130 mm Hg, and the pulse pressure
      decreased. Shortly after intravenous administration of nitroglycerin (0.5 mg),
      central aortic pressure decreased and the peak systolic gradient increased to 100
      mm Hg. On the first sinus beat after a premature ventricular contraction, the
      peak systolic gradient increased to 160 mm Hg, and the pulse pressure decreased.
      Five minutes after intravenous nitroglycerin, the peak systolic gradient returned
      to 70 mm Hg. Follow-up transthoracic echocardiography 13 days later showed normal
      left ventricular wall motion with no pressure gradient through the left
      ventricular outflow tract.

PMID- 17027332
TI  - Don't miss extra-cardiac manifestations of familial left ventricular
      hypertrabeculation/non-compaction.

PMID- 17027333
TI  - Sleep-disordered breathing in patients with symptomatic heart failure: a
      contemporary study of prevalence in and characteristics of 700 patients.
AB  - AIM: Evaluation of the prevalence and nature of sleep-disordered breathing (SDB)
      in patients with symptomatic chronic heart failure (CHF) receiving therapy
      according to current guidelines. METHODS AND RESULTS: We prospectively screened
      700 patients with CHF (NYHA class> or =II, LV-EF< or =40%) for SDB using
      cardiorespiratory polygraphy (Embletta). Furthermore, echocardiography,
      cardiopulmonary exercise and 6-min walk testing were performed. Medication
      included ACE-inhibitors and/or AT1-receptor blockers in at least 94%, diuretics
      in 87%, beta-blockers in 85%, digitalis in 61% and spironolactone in 62% of
      patients. SDB was present in 76% of patients (40% central (CSA), 36% obstructive
      sleep apnoea (OSA)). CSA patients were more symptomatic (NYHA class 2.9+/-0.5 vs.
      no SDB 2.57+/-0.5 or OSA 2.57+/-0.5; p<0.05) and had a lower LV-EF (27.4+/-6.6%
      vs. 29.3+/-2.6%, p<0.05) than OSA patients. Oxygen uptake (VO(2)) was lowest in
      CSA patients: predicted peak VO(2) 57+/-16% vs. 64+/-18% in OSA and 63+/-17% in
      no SDB, p<0.05. 6-min walking distances were 331+/-111 m in CSA, 373+/-108 m in
      OSA and 377+/-118 m in no SDB (p<0.05). CONCLUSIONS: This study confirms the high
      prevalence of SDB, particularly CSA in CHF patients. CSA seems to be a marker of
      heart failure severity.

PMID- 17027334
TI  - Prescription of beta-blockers in patients with advanced heart failure and
      preserved left ventricular ejection fraction. Clinical implications and survival.
AB  - BACKGROUND: The effects of beta-blockers in patients with heart failure (HF) and
      preserved left ventricular ejection fraction (LVEF) are not well established.
      AIMS: To assess the association between beta-blocker prescription at discharge
      and mortality in a cohort of patients with advanced HF and preserved LVEF.
      METHODS AND RESULTS: We prospectively studied a cohort of 443 patients with
      advanced HF and preserved LVEF (LVEF> or =40%). Mean age was 78 years, 56%
      female, 33% NYHA class IV. Overall, 227 patients (51%) had a beta-blocker
      prescribed at discharge. Mean duration of follow-up was 25 (+/-18) months. Death
      (all cause) occurred in 40 patients (17.6%) who were receiving a beta-blocker at
      discharge and 73 patients (33.8%) who were not on a beta-blocker. In multivariate
      Cox analysis, including adjustment for propensity score, prescription of a beta
      blocker remained associated with a 43% relative mortality risk reduction (HR
      0.57, 95% CI 0.37 to 0.88, p=0.01). CONCLUSIONS: In this cohort of patients with
      advanced HF and preserved LVEF, prescription of a beta-blocker was associated
      with a significant mortality reduction. This beneficial effect of beta-blocker
      use needs to be further confirmed in prospective, randomised clinical trials.

PMID- 17027335
TI  - B-type natriuretic peptide levels predict event-free survival in patients with
      implantable cardioverter defibrillators.
AB  - INTRODUCTION: We examined whether B-type natriuretic peptide (BNP) levels predict
      outcome in heart failure patients with implantable cardioverter defibrillators
      (ICD) using a combined endpoint of malignant tachyarrhythmias, death or heart
      transplantation. METHODS AND RESULTS: BNP levels were measured in 123 ICD
      patients with chronic heart failure (age: 63+/-12 years, ejection fraction: 29+/
      10%). After a median follow-up of 25 months, the combined endpoint was reached in
      28 patients (first tachyarrhythmic event, n=16; death, n=11; heart
      transplantation, n=1). BNP levels were significantly lower in patients with event
      free survival compared to patients reaching the combined endpoint of this study
      (median: 140 vs. 373 pg/ml; p<0.001). Multivariable Cox regression analysis
      revealed that BNP levels predict adverse outcome (RR 1.002 per pg/ml increment;
      95% CI: 1.001-1.003; p<0.001) and use of beta-blockers was associated with
      favourable outcome (RR 0.319; 95% CI 0.151-0.670; p=0.004). LV ejection fraction
      (p=0.66) did not significantly predict event-free survival in multivariable
      analysis. CONCLUSIONS: BNP plasma levels are useful markers to predict event-free
      survival in ICD patients with heart failure. Of note, malignant tachyarrhythmias
      appear responsible for about 50% of fatal outcomes. Our findings suggest that
      determination of BNP plasma levels is more valuable than determining LV ejection
      fraction to anticipate event-free survival in this population.

PMID- 17027336
TI  - Metabolic disturbances in chronic heart failure: a case for the "macho" approach
      with testosterone?!
AB  - Chronic heart failure (CHF) primarily affects the cardiovascular system. In
      addition, there is strong evidence that CHF is a complex metabolic disorder.
      Metabolic abnormalities include insulin resistance and lack of anabolic hormone
      activity. To date there have been few interventional trials targeting insulin
      sensitivity. A recent study suggests a link between testosterone therapy and
      improvements in insulin sensitivity, measured using the homeostatic model
      assessment (HOMA-IR). We discuss this study in detail. Further studies are needed
      to substantiate this link and to generally explore the value of testosterone
      therapy in CHF patients.

PMID- 17027337
TI  - Identification and characterization of "pathoadaptive mutations" of the cadBA
      operon in several intestinal Escherichia coli.
AB  - The dysenteric Shigella spp. and enteroinvasive Escherichia coli (EIEC) have
      evolved from commensal E. coli by the acquisition of a virulence plasmid and
      inactivation of genes of the cad locus encoding lysine decarboxylase (LDC) by so
      called pathoadaptive mutation. As horizontal gene transfer and recombination
      occurs frequently in E. coli we were interested to see if similar pathoadaptive
      mutations are commonly present in other intestinal pathotypes. Therefore, we
      examined 140 intestinal E. coli strains of various pathotypes and the ECOR
      collection for their ability to decarboxylate lysine, and identified 25 strains
      that were unable to do so. Complementation of a Shiga toxin-producing E. coli and
      two enteropathogenic E. coli strains, both LDC-negative, with the intact cad
      locus restored LDC activity and resulted in a reduction in adherence to tissue
      culture cells. We investigated the cad locus for possible alterations by using
      hybridization and PCR techniques and compared the results with the alterations
      reported for Shigella spp. and EIEC strains. Interestingly, the alterations of
      the cad genes were similar to those previously reported, pointing towards a
      parallel evolution of LDC silencing in different intestinal E. coli pathotypes.

PMID- 17027338
TI  - Cannabinoid receptors as therapeutic targets for obesity and metabolic diseases.
AB  - One of the most interesting pharmacological targets proposed in the past ten
      years for fighting obesity and related metabolic disorders is the endocannabinoid
      system. The role of the endocannabinoid system is crucial in regulating the
      rewarding properties of food, in controlling energy balance by acting at the
      hypothalamic circuitries involved in food intake, and in peripheral metabolism by
      influencing adipocytes, hepatocytes, myocytes and pancreatic endocrine cells.
      Obesity seems to be a condition associated with a pathological overactivation of
      the endocannabinoid system; therefore, restoring a normal endocannabinoid tone by
      antagonizing the cannabinoid receptor type 1 (CB(1)) could help arrest both the
      development and the maintenance of obesity.

PMID- 17027339
TI  - Understanding the molecular causes of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease that is both common and
      incurable. The majority of cases are sporadic and of unknown origin but several
      genes have been identified that, when mutated, give rise to rare, familial forms
      of the disease. The principal genes that have been shown to cause PD are alpha
      synuclein (SNCA), parkin, leucine-rich repeat kinase 2 (LRRK2), PTEN-induced
      putative kinase 1 (PINK1) and DJ-1. Here, we discuss what has been learnt from
      the study of these genes and what has been elucidated of the molecular pathways
      that lead to cell degeneration. Of importance is what these molecular events and
      pathways tell scientists of the common sporadic form of PD. Although complete
      knowledge of these genes' functions remains elusive, recent work implicates
      abnormal protein accumulation, protein phosphorylation, mitochondrial dysfunction
      and oxidative stress as common pathways to PD pathogenesis.

PMID- 17027341
TI  - Electrical induction of spikes in the hippocampus impairs recognition capacity
      and spatial memory in rats.
AB  - In clinical studies, interictal EEG spikes (IS) have been associated with
      numerous neuropsychological abnormalities, ranging from transitory cognitive
      impairment to epileptic encephalopathies. Understanding the pathophysiological
      mechanisms of IS has been hampered by the lack of validated animal models. To
      mimic IS, a stimulating microelectrode was implanted in the ventral hippocampal
      commissure and a recording microelectrode in the CA1 region of the hippocampus of
      normal male rats. Spike patterns were induced using a series of electrical pulses
      10-30 ms in duration with a frequency of 0.5-2Hz and a current of 0.2mA. The
      commissural stimulation-evoked population discharges in the hippocampus resembled
      naturally occurring IS in epileptic rats and, in no cases, resulted in behavioral
      seizures. For behavioral testing, the Morris water maze, radial arm maze, and
      object recognition tasks were used. Spikes were induced during sleep between the
      two sets of water maze trials; during the trials in the radial arm maze task; and
      prior to the sample phase and during the delay periods in the object recognition
      task. We demonstrated that rats that received spikes took longer to reach the
      escape platform in the second set of water maze trials; had significantly more
      reference errors and required more trials to complete the radial arm maze task;
      and had lower investigation ratios in the object recognition task. The results
      indicate that induction of spikes in the hippocampus results in impairment of
      spatial reference and nonspatial object recognition memory.

PMID- 17027340
TI  - Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy
      are normalized by impairment of brain corticotropin-releasing factor.
AB  - Social interaction phenotyping is an unexplored niche in animal modeling of
      epilepsy despite the sensitivity of affiliative behaviors to emotionality and
      stress, which are known seizure triggers. Thus, the present studies examined the
      social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in
      untreated animals and following preexposure to a handling stressor. The second
      aim of the present studies was to evaluate the dependence of sociability in El
      mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor
      (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively
      reduced CRF peptide levels in the basolateral amygdala of El mice. El mice
      exhibited lower social investigation times than ddY counterparts, whereas central
      administration of CRF-SAP normalized social investigation times relative to ddY
      controls. Moreover, handling-induced seizures in El mice were reduced by 50%
      following treatment with CRF-SAP relative to saporin alone-injected El controls.
      The results of this study suggest that tonically activated CRF systems in the El
      mouse brain suppress affiliative behavior and facilitate evoked seizures.

PMID- 17027342
TI  - Removed: Integrative differential gene expression analysis for cross-platform
      microarray datasets.
AB  - This article has been removed, consistent with Elsevier Policy on Article
      Withdrawal. Please see . The Publisher apologizes for any inconvenience this may
      cause.

PMID- 17027343
TI  - Evaluation of a brief cardiovascular autonomic screen.
AB  - OBJECTIVE: To test the validity and practicality of a simple, rapid autonomic
      cardiovascular evaluation (RACE). INTRODUCTION: Assessment of the autonomic
      nervous system is costly and time consuming. Consequently, briefer measures are
      often utilized as evaluations of autonomic function. We therefore set out to
      assess the validity and practicality of a simple, rapid autonomic cardiovascular
      evaluation protocol which mimicked the bedside evaluations used in many
      healthcare centers. DESIGN/METHODS: Every eligible patient undergoing full
      autonomic testing (FAT) in our laboratory was enrolled. The protocol, performed
      blinded to FAT results, consisted of one breath in the supine position, and
      supine and standing (1 and 3 min) pressures and pulse. Results were scored for
      cardiac variation during the breath, a drop in pressure during the stand. Pulse
      increase was also scored. Aggregate RACE score was regressed against a similarly
      scored FAT. RESULTS: The single breath response correlated poorly with the
      standard response to deep breathing with convergent results in only 26/37
      patients, with a specificity of 30%, and sensitivity of 85%. HR and BP changes
      standing showed little regression against matching values during FAT. Only 5/11
      patients who met the criteria for postural tachycardia syndrome by FAT
      demonstrated a >20 bpm increase in HR by 3 min standing. Finally, aggregate
      scores for FAT and RACE correlated poorly. DISCUSSION: The RACE does not satisfy
      the criteria to serve as a robust dysautonomia screen. Full autonomic testing
      provides more complete and accurate information than simple bedside assessment.

PMID- 17027344
TI  - Genetic heterogeneity among visceral and post-Kala-Azar dermal leishmaniasis
      strains from eastern India.
AB  - In India and Sudan, some patients of visceral leishmaniasis develop post-Kala
      Azar dermal leishmaniasis (PKDL) while majority will not. Similarly, the clinical
      manifestations and treatment outcome are reported to vary from district to
      district and state to state in India. Present study is focused on to find out the
      genetic variations between VL & PKDL causing strains. Nuclear DNA from 24 strains
      of Leishmania donovani, isolated from patients of visceral leishmaniasis (18) and
      PKDL (6) was extracted and digested with PstI restriction enzyme followed by
      southern hybridization using Dig labeled beta-tubulin as probe. The results
      showed three different banding patterns among 18 VL strains. However, all PKDL
      isolates showed a genetic homogeneity within themselves but heterogeneity from VL
      isolates. Interestingly maximum heterogenic groups were found in Bihar but all
      isolates from West Bengal showed a single genotype origin. This study shows that
      genetic mutations might be responsible for such variation and development of PKDL
      in visceral strains of Indian L. donovani.

PMID- 17027345
TI  - BRCA1 ubiquitylation of CtIP: Just the tIP of the iceberg?
AB  - Ubiquitylation is an important regulatory mechanism of many cellular processes.
      The breast and ovarian cancer-specific tumour suppressor BRCA1 is well
      acknowledged to be a RING/E3 ubiquitin ligase, however, identification of its
      physiological substrates has proved elusive. Recently published data have shown
      that the BRCA1-interacting protein CtIP is in fact ubiquitylated by BRCA1, and
      opens new avenues for the isolation of other substrate proteins.

PMID- 17027346
TI  - A specific database for providing local and national level of integration of
      clinical data in cystic fibrosis.
AB  - It has recently been stated that a database is an essential tool in the
      management of CF. The purpose of this work is to create a specific database
      allowing optimal performance of storage, search and retrieval functions on
      patients with CF. A specific database was developed using a Windev licence, for
      application via Microsoft supported platforms or Intranet system. The database
      allows real-time point of care data management of medical, investigational and
      administrative data. It is currently being used in the 6 Belgian reference
      centres. It represents a useful tool for gathering information on routine
      clinical and lab data, bacteriology, treatments, complications and specific
      outcomes for clinical and research purposes. The ongoing evolution of the
      database includes enhancements toward research data orientation including
      comparison of patient data between different centres and completeness of the
      National CF registry questionnaire. A complimentary copy of the software can be
      provided to multidisciplinary accredited CF centres worldwide upon request.

PMID- 17027347
TI  - Long-term facilitation of breathing is absent after episodes of hypercapnic
      hypoxia in awake humans.
AB  - Despite the failure by many previous investigators to demonstrate a long-term
      facilitation of breathing following episodes of hypoxia in awake humans, we
      attempted to produce it using a pattern of hypercapnic hypoxic episodes similar
      to that experienced by obstructive sleep apnoea patients, reasoning that if long
      term facilitation was relevant to these patients then it is appropriate to test
      the effectiveness of such episodes. Ten subjects drawn from the University
      student population were instrumented to measure ventilation, heart rate and end
      tidal PCO2 and PO2 breath-by-breath while seated in a comfortable reclining
      chair. After an initial resting period breathing room air they experienced
      fifteen, 30-s episodes breathing 6% O2 and 5% CO2 separated by 90 s of breathing
      air. We examined the measured variables for an hour after the episodes but found
      no trends toward an increase in ventilation or decrease in end-tidal PCO2 that
      would indicate the presence of a long-term facilitation. We therefore concluded
      that long-term facilitation of ventilation was not demonstrated in awake humans
      using this pattern of stimuli.

PMID- 17027348
TI  - Recurrent obstructive apneas trigger early systemic inflammation in a rat model
      of sleep apnea.
AB  - Obstructive sleep apnea (OSA) is associated with vascular disorders possibly due
      to systemic inflammation. To determine whether repeated episodes of OSA in a rat
      model lead to endothelial cell activation and systemic leukocyte recruitment in
      the microcirculation. Three experimental groups (apnea, sham and naive) were
      studied. The apnea group was instrumented and subjected to repeated obstruction
      for 3h (rate 60/h, length 5s) using a special device. The sham group was only
      instrumented and the naive group was used as a control. Leukocyte-endothelial
      cell interactions (intravital microscopy) and expression of P-selectin
      (immunohistochemistry) were determined in colonic venules. The apnea group
      induced a significant increase in the flux of leukocytes rolling, number of
      rolling leukocytes and number of adherent leukocytes when compared with the sham
      or naive groups. P-selectin was up-regulated only in the apnea group. This
      experimental model of recurrent obstruction demonstrates rapid endothelial cell
      activation, suggesting the onset of an inflammatory response.

PMID- 17027349
TI  - Simple liquid chromatography-tandem mass spectrometry method for determination of
      novel anti-methicillin-resistant Staphylococcus aureus fluoroquinolone WCK 771 in
      human serum.
AB  - A simple, rapid, specific, precise, accurate and sensitive method for
      determination of WCK 771 in human serum has been developed. The method uses high
      performance liquid chromatography with tandem mass spectrometric detection.
      Sample preparation involves protein precipitation method by addition of
      acetonitrile. Gatifloxacin was used as internal standard. The response was found
      to be linear from 0.312 to 40 microg/ml of serum with correlation coefficient
      greater than 0.99. Limit of detection and lower limit of quantification for WCK
      771 was found to be 0.078 microg/ml and 0.312 microg/ml, respectively. The intra
      day precision and accuracy from analysis of quality control (QC) samples at four
      concentrations was in the range of 2.36-2.58% and from 96.71 to 103.2%,
      respectively. The inter-day precision and accuracy from analysis of quality
      control samples at four concentrations was in the range of 3.14-6.82% and from
      96.84 to 105.76%, respectively. WCK 771 was found to be stable for 24 h at auto
      injector environment. WCK 771 was also found to be stable for 2h in serum at 25+/
      3 degrees C and for 3 months at -20 degrees C. Mean absolute recovery at four
      different concentrations was 86.92% with standard deviation of 1.79. Throughput
      of the method is approximately one sample every 4 min. The method was also
      reproduced with monkey serum. The method was employed for estimation of drug
      serum levels during pre-clinical and clinical trials.

PMID- 17027350
TI  - Optimal operation conditions for protein separation in hydrophobic interaction
      chromatography.
AB  - Protein retention in hydrophobic interaction chromatography is determined by
      protein physicochemical properties and by system characteristics. In this paper
      we present an attempt to determine the optimal operation conditions that would
      allow the separation of binary protein mixtures. The statistically significant
      system variables were determined, and then empirical models were obtained which
      explained more than 92% of variability in dimensionless retention time based on
      salt properties, ionic strength of the initial eluent and substitution degree of
      the resin. These variables were optimized in order to achieve the maximum
      retention time difference between two proteins in a mixture. The optimum
      operation conditions as predicted by the models were tested experimentally,
      showing a good agreement with predicted separation. We concluded that it would be
      possible to determine the system conditions that allow the maximum separation of
      two proteins based on the main system properties. The methodology proposed here
      presents potential to be applied to partially characterized systems, however, it
      could be improved if protein's properties were included explicitly in the models.

PMID- 17027351
TI  - Comparison of the internal dynamics of globular proteins in the microcrystalline
      and rehydrated lyophilized states.
AB  - Natural abundance solid-state 13C-NMR spin-lattice relaxation experiments in the
      laboratory (T1) and off-resonance rotating (T(1rho)) frames were applied for
      qualitative comparison of the internal molecular dynamics of barstar, hen egg
      white lysozyme and bacteriophage T4 lysozyme in both the microcrystalline and the
      rehydrated (water content is 50% of the protein mass) lyophilized states. The
      microcrystalline state of proteins provides a better spectral resolution;
      however, less is known about the local structure and dynamics in the different
      states. We found by visual comparison of both T1 and T(1rho) relaxation decays of
      various resonance bands of the CPMAS spectra that within the ns-mus range of
      correlation times there is no appreciable difference in the internal dynamics
      between rehydrated lyophilized and crystalline states for all three proteins
      tested. This suggests that the internal conformational dynamics depends weakly if
      at all on inter-protein interactions in the solid state. Hence, physical
      properties of globular proteins in a fully hydrated solid state seem to be
      similar to those in solution. This result at least partly removes concerns about
      biological relevance of studies of globular proteins in the solid state.

PMID- 17027353
TI  - The second National Institutes of Health International Congress on advances in
      uterine leiomyoma research: conference summary and future recommendations.
AB  - OBJECTIVE: To summarize the proceedings of the Advances in Uterine Leiomyoma
      Research: 2nd NIH International Congress, which was convened on February 24-25,
      2005 by the Department of Health and Human Services (DHHS), National Institutes
      of Health (NIH) in Bethesda, Maryland. DESIGN: Scientific information was
      presented at a 2-day conference, which was a collaborative effort of agencies
      across the DHHS and members of the academic, clinical, and medical communities
      involved in uterine leiomyoma research. CONCLUSION(S): The conference brought
      together scientists in biomedicine, epidemiology, basic research, therapeutics,
      and translational medicine and fostered an exchange of scientific information
      among members of the uterine leiomyoma research and health care communities. This
      document summarizes this exchange and outlines research needs and recommendations
      for future research directions.

PMID- 17027354
TI  - Toward developing a once-a-month pill: a double-blind, randomized, controlled
      trial of the effect of three single doses of mifepristone given at midcycle on
      the pattern of menstrual bleeding.
AB  - OBJECTIVE: To test the feasibility of timing the administration of mifepristone
      as a once-a-month contraceptive pill on the 12th day before the next menses, as
      calculated from the length of the previous menstrual cycles. DESIGN: Double
      blind, randomized, controlled trial. SETTING: Five family planning centers across
      the world. PATIENT(S): Three hundred ninety-nine women attending family planning
      clinics. INTERVENTION(S): Randomized to receive 10, 25, or 200 mg of mifepristone
      or a placebo. MAIN OUTCOME MEASURE(S): Lengthening or shortening of the normal
      menstrual cycle length following administration of the drug by at least 5 days.
      RESULT(S): The menstrual period came within 5 days of the predicted date in 88%
      of women receiving the placebo, 84% of women receiving 10 mg, 72% of women
      receiving 25 mg of mifepristone, and only 48% of women treated with 200 mg of
      mifepristone. Increasing the dose of mifepristone was associated with an
      increased chance of having a delayed period (P<.001). Only 45% of women were in
      the peri-ovulatory phase of the cycle according to LH and P measurements on the
      day of drug administration. Women treated before ovulation were more likely to
      have delayed menses with all three doses of mifepristone. CONCLUSION(S): Because
      of the disruption in cycle length, it appears unlikely that mifepristone
      administered once a month, at a calendar-based time, would provide a reliable
      method of contraception.

PMID- 17027355
TI  - Prediction of embryo developmental potential and pregnancy based on early stage
      morphological characteristics.
AB  - OBJECTIVE: To analyze the association between morphological details at different
      stages of culture with blastocyst development, with an aim to improve selection
      for transfer. DESIGN: Retrospective audit of data. SETTING: Tertiary referral
      center and university hospital. PATIENT(S): Two hundred sixty-eight couples
      underwent 357 treatment cycles. INTERVENTION(S): Oocyte pickups for IVF or
      intracytoplasmic sperm injection (ICSI) after ovarian stimulation. Embryos were
      individually cultured and examined on days 0-2 for morphological details and
      developmental characteristics, and selected for transfer, freezing, or further
      culture. MAIN OUTCOME MEASURES: The association of blastocyst development and
      pregnancy with morphological characteristics. RESULT(S): Five morphological
      characteristics (appearance of the cytoplasm, pronuclei and nucleoli, cytoplasmic
      deficit, and developmental rate) showed the strongest association with blastocyst
      development. By combining information from all days of culture into a cumulative
      score, prediction was greatly improved, compared to only using day 2 morphology.
      Cytoplasmic dysmorphisms of the oocyte, including accumulation of smooth
      endoplasmic reticulum, were associated with poor developmental performance.
      Differential weighting of these characteristics was included in a new embryo
      scoring system, which showed a strong correlation with implantation.
      CONCLUSION(S): Weighting individual morphological characteristics of zygotes and
      embryos and combining them into a cumulative embryo score can improve selection
      of embryos for transfer.

PMID- 17027356
TI  - Association between androgen receptor gene CAG trinucleotide repeat length and
      testicular histology in older men.
AB  - OBJECTIVE: To determine whether the size of CAG repeat in exon 1 of the androgen
      receptor (AR) gene is related to impaired spermatogenesis in older men. DESIGN:
      Study of two groups of older men: one with preserved spermatogenesis and the
      other with arrested spermatogenesis. SETTING: University teaching hospital.
      PATIENT(S): Twenty-eight men aged from 53 to 102 years. INTERVENTION(S): The DNA
      fragment encoding the AR polyglutamine tract was amplified from DNA of testis
      tissue. MAIN OUTCOME MEASURE(S): The size of the CAG repeat was evaluated by
      using fluorescent-labeled polymerase chain reaction performed on an ABI Prism 377
      DNA sequencer followed by automated analysis with Genscan 3.1.2 software.
      RESULT(S): Mean CAG repeat length was 22.76 +/- 3 in the group of 13 aged men
      with preserved spermatogenesis and 21.86 +/- 2.23 in the group of 15 aged men
      with arrested spermatogenesis. CONCLUSION(S): Impaired spermatogenesis in elderly
      men does not seem to be correlated with the AR gene CAG repeat length, which
      therefore does not appear to be a risk factor for impaired spermatogenesis in
      older men.

PMID- 17027357
TI  - Reactive oxygen species as an independent marker of male factor infertility.
AB  - OBJECTIVE: To determine the abnormal patterns of reactive oxygen species (ROS)
      production in male factor infertility (MFI) patients and to define the ROS
      reference values in such patients. DESIGN: A retrospective study. SETTING: Male
      infertility clinic at a tertiary healthcare center. PATIENT(S): We examined 132
      MFI patients (all normal sperm parameters, n = 24, and all abnormal sperm
      parameters, n = 38) and 34 healthy donors. INTERVENTION(S): Routine semen
      analysis, measurement of ROS. MAIN OUTCOME MEASURE(S): Sperm parameters, ROS
      levels (10(4) cpm/20 x 10(6) sperm). RESULT(S): Normal, healthy donors had
      significantly higher (P<.0001) sperm concentration, motility, and morphology
      compared with all MFI patients. Univariate analysis indicated a significant
      association between MFI and log (ROS + 1) (odds ratio [OR] = 3.84), besides sperm
      parameters and age. A multivariate model using logistic regression analysis also
      indicated an independent association of log ROS with MFI (OR = 4.25). The ROS
      cutoff values of 1.2-1.4 had a sensitivity of 0.70-0.78 with a corresponding
      specificity of 0.82. However, at a cutoff point of 1.2, the OR was 68.6, which
      increased with an increase in the cutoff. CONCLUSION(S): High ROS is an
      independent marker of MFI, irrespective of whether these patients have normal or
      abnormal semen parameters. We suggest the inclusion of ROS measurement as part of
      idiopathic infertility evaluation. Treatment with antioxidants may be beneficial
      in such patients.

PMID- 17027358
TI  - Pubertal evaluation of adolescent boys with beta-thalassemia major and delayed
      puberty.
AB  - OBJECTIVE: To examine the hormonal status of the hypothalamic-pituitary-gonadal
      axis in adolescent males with beta-thalassemia major. DESIGN: Controlled clinical
      study. SETTING: Tertiary referral teaching hospital. PATIENT(S): Thirty-three
      adolescent males with beta-thalassemia major. INTERVENTION(S): Basal LH, FSH, and
      T were examined. All individuals received 100 microg GnRH analogue. Four hours
      later the hormone levels were retested. Patients with beta-thalassemia and low T
      levels received hCG. MAIN OUTCOME MEASURE(S): The preintervention and
      postintervention levels of FSH, LH, and T were examined. RESULT(S): Of the 33
      beta-thalassemia major adolescents, 17 had delayed puberty. The difference in
      basal LH, FSH, and T levels between delayed and normal puberty beta-thalassemia
      groups were statistically significant. These levels were significantly lower
      compared with the constitutional delayed puberty group and become even more
      significant after GnRH analogue administration. The T levels in the beta
      thalassemia group were significantly lower than in the control group. After hCG
      administration, the T levels remained significantly lower in the delayed-puberty
      beta-thalassemia compared to the normal-puberty beta-thalassemia group.
      CONCLUSION(S): Despite recent therapeutic advances in the management of beta
      thalassemia major, the risk of secondary endocrine dysfunction remains high.
      Hypogonadism is one of the most frequent endocrine complications.

PMID- 17027359
TI  - Interleukin-18 system messenger RNA and protein expression in human endometrium
      during the menstrual cycle.
AB  - OBJECTIVE: To investigate the IL-18 system, including IL-18, IL-18 receptor (IL
      18R), IL-18 binding protein (IL-18BP), and IL-18 precursor (proIL-18), mRNA and
      protein expression in human endometrium during the menstrual cycle. DESIGN:
      Controlled study. SETTING: Clinical and academic research setting in a university
      medical center. PATIENT(S): Human endometrium was obtained from surgical
      specimens of normal cycling women undergoing hysterectomy for benign reasons.
      INTERVENTION(S): A total of 24 human endometrium samples were obtained at
      proliferative and secretory phase from surgical specimens of normal cycling women
      undergoing hysterectomy. Quantitative competitive polymerase chain reaction (QC
      PCR) and immunohistochemistry were performed. MAIN OUTCOME MEASURE(S): The
      differences of IL-18 system mRNA and the ratio of antagonist to agonist in both
      proliferative and secretory phases of endometrium were analyzed. RESULT(S): Our
      results showed a complete IL-18 system, including mRNA expression and protein
      production in both proliferative and secretory phases of the endometrium. The QC
      PCR demonstrated that both IL-18 and IL-18R decreased and IL-18BP increased mRNA
      expression in human endometrium in secretory phase compared with proliferative
      phase. A positive correlation of IL-18 and IL-18R in human endometrium was
      demonstrated in proliferative phase but not in secretory phase. In addition,
      there is a significantly higher ratio of IL-18BP to IL-18 mRNA levels in
      secretory endometrium compared with proliferative phase endometrium (P<.05).
      CONCLUSION(S): The expression and ratio of IL-18 antagonist to agonist may be
      responsible for embryo implantation.

PMID- 17027360
TI  - Serum sex hormone-binding globulin levels show too much variability to be used
      effectively as a screening marker for insulin resistance in women with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To evaluate the relationship between serum sex hormone-binding
      globulin (SHBG) and parameters of insulin sensitivity in women with polycystic
      ovary syndrome (PCOS) and controls, and determine the feasibility of using SHBG
      levels to predict insulin resistance. DESIGN: Evaluation of a prospectively
      collected database. SETTING: University reproductive center. PATIENT(S): A total
      of 21 women with PCOS and 17 controls. INTERVENTION(S): Oral glucose tolerance
      test. MAIN OUTCOME MEASURE(S): Correlations of serum SHBG and parameters of
      insulin sensitivity. RESULT(S): [1] Among all participants, SHBG levels indicated
      a correlation between the fasting glucose-to-insulin (GI) ratio and the
      quantitative insulin sensitivity check index (QUICKI). Participants with PCOS
      demonstrated significant correlations of SHBG and fasting GI ratio, 1-hour
      postglucola insulin levels, and random 17-hydroxyprogesterone (17ohP4) levels.
      Among controls, SHBG and fasting serum glucose and 2-hour postglucola serum
      glucose levels were associated. [2] Participants with PCOS and lean controls
      exhibited different glucose and insulin responses to 75 g of glucose at 1 and 2
      hours postchallenge, resulting in paradoxically similar GI ratios. CONCLUSION(S):
      [1] Although certain parameters of insulin status and serum SHBG demonstrated
      statistically significant correlation coefficients, these relationships are weak
      and SHBG cannot be used as a predictor of insulin resistance. [2] The post
      glucose load GI ratio cannot be used to determine the magnitude of insulin
      resistance.

PMID- 17027361
TI  - Preimplantation genetic diagnosis of Marfan syndrome using multiple displacement
      amplification.
AB  - OBJECTIVE: To evaluate the use of multiple displacement amplification (MDA) for
      whole-genome amplification in the preimplantation genetic diagnosis (PGD) of
      Marfan syndrome. DESIGN: Multiple displacement amplification was used to amplify
      the whole-genome directly from a single cell. The MDA product was used for
      polymerase chain reaction (PCR) analysis of five different loci. At this point
      MDA was used to develop a PGD-Marfan syndrome program. SETTING: Fertility and
      gynecology private center in Alicante, Spain. PATIENT(S): A couple in which the
      husband is affected by Marfan syndrome and carries a novel mutation in the FBN-1
      gene. INTERVENTION(S): The MDA of single cells and PCR tests for PGD. MAIN
      OUTCOME MEASURE(S): Allele drop-out (ADO), amplification efficiency rates, and
      the ability to detect Marfan syndrome using MDA. RESULT(S): We report that
      isothermal whole-genome amplification from single cells allowed analysis of five
      different loci using standard conditions. The development of a MDA-PGD protocol
      for Marfan syndrome allowed for the diagnosis of seven embryos. These were
      biopsied on day 3 of culture and analyzed. Two healthy embryos were transferred
      48 hours after culture, resulting in a singleton ongoing pregnancy and the birth
      of a healthy child. CONCLUSION(S): The MDA technique is useful for overcoming the
      problem of insufficient genomic DNA in PGD. The use of MDA as a universal step
      marks a new cycle for PGD as it allows for the diagnosis of any known gene defect
      by standard methods and conditions.

PMID- 17027363
TI  - Presence of hydrosalpinx correlated to endometrial inflammatory response in vivo.
AB  - OBJECTIVE: To evaluate and compare the inflammatory response and mediators in the
      endometrium of patients with hydrosalpinges compared with normal controls.
      DESIGN: Retrospective case-control study. SETTING: Urban medical center.
      PATIENT(S) AND INTERVENTION(S): Hysterectomy samples were identified as being
      affected by hydrosalpinx or salpingitis (n = 30) and were age-matched with
      control samples (n = 30). INTERVENTIONS: Fallopian tube and endometrial slides
      were analyzed for leukocytes and immunohistochemical techniques performed for
      cytokines (interleukin-2 [IL-2]). MAIN OUTCOME MEASURE(S): Evaluate and compare
      the endometrial inflammatory response (leukocytes and cytokines) from samples
      affected and non-affected by hydrosalpinx and salpingitis. RESULT(S): Examination
      of tubal and endometrial slides with hydrosalpinx demonstrated a statistically
      significant increase in the number of overall inflammatory cells. High-intensity
      immunohistochemical staining for IL-2 was demonstrated in 7.4% of controls versus
      65% of cases. CONCLUSION(S): A defined, identifiable, local response to
      hydrosalpingeal fluid has been demonstrated in the endometrium. This response
      consists of statistically significant elevations of leukocytes and IL-2. An
      inflammatory endometrial response may be an independent contributor to the
      decreased reproductive outcome observed in patients with hydrosalpinges.

PMID- 17027362
TI  - A randomized prospective study of misoprostol or mifepristone followed by
      misoprostol when needed for the treatment of women with early pregnancy failure.
AB  - OBJECTIVE: To compare the effectiveness and safety of misoprostol and
      mifepristone, followed when needed by misoprostol, for the treatment of women
      with early pregnancy failure. DESIGN: Prospective randomized nonblinded
      controlled trial. SETTING: University-affiliated tertiary medical center.
      PATIENT(S): One hundred fifteen consecutive women diagnosed as having a blighted
      ovum or missed abortion of <9 weeks of gestation enrolled. INTERVENTION(S): The
      patients received orally 600 mg mifepristone (group I) or orally 800 microg
      misoprostol (group II). Most patients in both groups subsequently received 48
      hours later orally 800 microg misoprostol. MAIN OUTCOME MEASURE(S): Failure was
      defined as surgical intervention due to retained gestational sac 48 hours after
      completion of the drug protocol, severe symptoms, or suspected retained products
      of conception after the menstrual period. RESULT(S): The success rate was similar
      in groups I and II: 38 of 58 patients (65.5%) versus 42 of 57 patients (73.6%),
      respectively. No cases of severe infection or bleeding necessitating blood
      transfusion occurred. CONCLUSION(S): Misoprostol is an effective and safe
      treatment for early pregnancy failure and could replace surgical curettage in
      over two-thirds of the patients. Mifepristone offers no advantage compared with
      misoprostol as initial treatment.

PMID- 17027364
TI  - Early postoperative changes in testosterone, dehydroepiandrosterone sulfate, and
      sex hormone-binding globulin after hysterectomy with or without concomitant
      oophorectomy.
AB  - OBJECTIVE: To investigate the cross-sectional associations of hysterectomy and
      oophorectomy status, chronological age, and body mass index with early
      postoperative plasma levels of total and free T, DHEAS, and sex hormone-binding
      globulin (SHBG). DESIGN: A cross-sectional study. SETTING: University hospital.
      PATIENT(S): Ninety-two women age 35-47 years who were scheduled for hysterectomy
      and/or oophorectomy, advocated for benign gynecological pathologies.
      INTERVENTION(S): Ninety-two eligible premenopausal women underwent hysterectomy
      and/or oophorectomy, with plasma T, DHEAS, and SHBG levels assayed before surgery
      and during the postoperative period. MAIN OUTCOME MEASURE(S): Effects of time x
      operation and age x operation interactions between oophorectomized and
      nonoophorectomized groups and within-subject main effect of time on plasma
      androgen levels. RESULT(S): Of 92 women, hysterectomy alone was performed in only
      49 (53.3%) cases. Oophorectomy, either unilateral or bilateral, was performed in
      35.8% of cases. Age x within-group interactions exhibited an important difference
      (P=.03) in total T levels. The time x between- and within-group interaction
      effects on plasma DHEAS levels of postoperative day 7, compared with day 1, were
      statistically significant (P<.001). The effect of time x group interaction was
      remarkable, in terms of SHBG levels during the postoperative period. Age x
      oophorectomy interaction exhibited a statistically significant change of decline
      in DHEAS levels on postoperative day 7 (P=.05). CONCLUSION(S): The present study
      demonstrated a time and operation effect decline in plasma DHEAS levels. In
      contrast, the time x operation interaction on SHBG levels exhibited an increase
      toward postoperative day 7.

PMID- 17027366
TI  - Ectopic nucleolus organizer regions in a patient with premature ovarian failure.
AB  - OBJECTIVE: To present a case of premature ovarian failure (POF) and a complex
      chromosomal rearrangement involving band Xq21. DESIGN: Case report. SETTING:
      Department of cytogenetics, general analysis laboratory. PATIENT(S): A woman with
      POF and a complex translocation involving chromosomes X and 2 and a nucleolus
      organizer region (NOR) structure inserted in the critical region Xq21.
      INTERVENTION(S): Chromosomal analysis, NOR banding, hysteroscopy. MAIN OUTCOME
      MEASURE(S): Fluorescence in situ hybridization, comparative genome hybridization,
      human androgen receptor gene technique. RESULT(S): Four mechanisms may explain a
      causal relationship between the phenotype of the patient and her chromosome
      constitution. The presence of a NOR structure at the breakpoint of chromosome X
      suggests a complex reorganization and is of interest per se. CONCLUSION(S):
      Cytogenetic analysis is essential in women with unexplained POF and may provide
      valuable information on the chromosome location of critical regions implicated in
      ovarian function. However, in very complex reorganizations such as that described
      herein, classical cytogenetic techniques must be combined with molecular
      techniques to achieve a more complete characterization of the anomaly.

PMID- 17027365
TI  - Whole-arm translocations between chromosome 1 and acrocentric G chromosomes are
      associated with a poor prognosis for spermatogenesis: two new cases and review of
      the literature.
AB  - OBJECTIVE: To analyze unusual translocations involving a chromosome 1 whole arm
      and an acrocentric G chromosome p arm found in two men with azoospermia. DESIGN:
      Case report with review of the scientific literature. SETTING: Cytogenetics
      department. PATIENT(S): Two men with azoospermia and normal hormonal levels.
      INTERVENTIONS(S): Peripheral blood lymphocytes were obtained for karyotype, and
      metaphases were studied by standard GBG, RBG, and CBG banding procedures. MAIN
      OUTCOME MEASURE(S): Karyotype GBG, RBG, and CBG banding. RESULT(S): Karyotype
      revealed balanced translocation involving a chromosome 1 whole arm and an
      acrocentric G chromosome p arm: 46,XY,t(1;21)(q11;p13) (patient 1) and
      46,XY,t(1;22)(q11;p11) (patient 2). CONCLUSION(S): With regard to published cases
      of whole-arm translocation of human chromosome 1 with an acrocentric p arm and a
      maternal origin of these abnormalities, we argue for an impairment of meiosis
      resulting in a high probability of quadrivalent-XY-body interaction. Male factor
      infertility might be due to two poor prognostic factors, first the involvement of
      human chromosome 1 (and its heterochromatic region) and second the involvement of
      an acrocentric chromosome p-arm breakpoint. This probable interaction between the
      pachytene quadrivalent and XY body might explain azoospermia.

PMID- 17027367
TI  - Symptoms of premenstrual syndrome may be caused by hyperventilation.
AB  - OBJECTIVE: To determine whether women with premenstrual syndrome (PMS) differ
      from healthy women in the extent of hyperventilation during the luteal phase of
      the cycle. DESIGN: Case report. SETTING: Medical university. PATIENT(S): Three
      reproductive-age women with severe symptoms of PMS in whom dramatic decline in
      end-tidal PCO2 (PETCO2) occurred during the luteal phase of the cycle.
      INTERVENTION(S): Measurements of PETCO2, administration of GnRH agonist
      triptorelin. MAIN OUTCOME MEASURE(S): PETCO2 was determined daily by sidestream
      capnometry. RESULT(S): The decline in PETCO2 in women with PMS was 12-18 mm Hg,
      on the average. This was significantly more pronounced than the decline of PETCO2
      that was observed in healthy women. With the decline of PETCO2 the symptoms of
      PMS appeared. Symptoms disappeared at the end of the luteal phase when PETCO2 was
      increasing again. During treatment with the GnRH agonist, PETCO2 did not decline,
      and all women were free of symptoms. CONCLUSION(S): The symptoms of PMS observed
      in our patients were associated with a pronounced decline of PETCO2 that occurred
      during the luteal phase of the cycle. Because the symptoms were similar to
      symptoms observed in the chronic hyperventilation syndrome it is suggested that
      some symptoms of PMS may be caused by chronic hyperventilation. It appears that
      in women with PMS the sensitivity of the respiratory center to CO2 is increased
      more than normal by P or some other secretory product of the corpus luteum,
      resulting in pronounced hyperventilation with the associated clinical signs and
      symptoms of a chronic hyperventilation syndrome.

PMID- 17027368
TI  - Infertility in a man with oligoasthenoteratozoospermia associated with
      nonrobertsonian translocation t(9;15)(p10;q10).
AB  - OBJECTIVE: To analyze an unusual nonrobertsonian translocation t(9;15)(p10;q10)
      found in an infertile man with oligoasthenoteratozoospermia who had a normal
      phenotype. DESIGN: Case report with a review of scientific literature. SETTING:
      Academic research environment. PATIENT(S): Infertile man with
      oligoasthenoteratozoospermia but otherwise apparently healthy. INTERVENTION(S):
      Peripheral blood lymphocytes were obtained for karyotyping, and metaphases were
      studied by the GBG fluorescence in situ hybridization (FISH) procedure. MAIN
      OUTCOME MEASURE(S): Physical examination, semen analysis, GBG banding, and FISH
      procedure. RESULT(S): The semen analysis revealed oligoasthenoteratozoospermia.
      The lymphocytic karyotype detected a translocation t(9;15)(p10;q10), and FISH
      procedure showed that the derived chromosome had a chromosome 15 centromere.
      CONCLUSION(S): The association of unusual translocation with male factor
      infertility was described. To our knowledge no such association has been
      described previously in men whose clinical manifestation is only infertility.

PMID- 17027369
TI  - Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian
      failure.
AB  - Mutational screening of the bone morphogenetic protein 15 (BMP15) and growth
      differentiation factor 9 (GDF9) genes in a population with premature ovarian
      failure (POF) identified no new mutations. However, three single nucleotide
      polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and
      71C>G) and another in exon 1 (387G>A), were found to be common in both POF and
      control groups.

PMID- 17027370
TI  - Oxygen, cyanide and energy generation in the cystic fibrosis pathogen Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is a gram-negative, rod-shaped bacterium that belongs to
      the gamma-proteobacteria. This clinically challenging, opportunistic pathogen
      occupies a wide range of niches from an almost ubiquitous environmental presence
      to causing infections in a wide range of animals and plants. P. aeruginosa is the
      single most important pathogen of the cystic fibrosis (CF) lung. It causes
      serious chronic infections following its colonisation of the dehydrated mucus of
      the CF lung, leading to it being the most important cause of morbidity and
      mortality in CF sufferers. The recent finding that steep O2 gradients exist
      across the mucus of the CF-lung indicates that P. aeruginosa will have to show
      metabolic adaptability to modify its energy metabolism as it moves from a high O2
      to low O2 and on to anaerobic environments within the CF lung. Therefore, the
      starting point of this review is that an understanding of the diverse modes of
      energy metabolism available to P. aeruginosa and their regulation is important to
      understanding both its fundamental physiology and the factors significant in its
      pathogenicity. The main aim of this review is to appraise the current state of
      knowledge of the energy generating pathways of P. aeruginosa. We first look at
      the organisation of the aerobic respiratory chains of P. aeruginosa, focusing on
      the multiple primary dehydrogenases and terminal oxidases that make up the highly
      branched pathways. Next, we will discuss the denitrification pathways used during
      anaerobic respiration as well as considering the ability of P. aeruginosa to
      carry out aerobic denitrification. Attention is then directed to the limited
      fermentative capacity of P. aeruginosa with discussion of the arginine deiminase
      pathway and the role of pyruvate fermentation. In the final part of the review,
      we consider other aspects of the biology of P. aeruginosa that are linked to
      energy metabolism or affected by oxygen availability. These include cyanide
      synthesis, which is oxygen-regulated and can affect the operation of aerobic
      respiratory pathways, and alginate production leading to a mucoid phenotype,
      which is regulated by oxygen and energy availability, as well as having a role in
      the protection of P. aeruginosa against reactive oxygen species. Finally, we
      consider a possible link between cyanide synthesis and the mucoid switch that
      operates in P. aeruginosa during chronic CF lung infection.

PMID- 17027371
TI  - Structure, mechanism and physiological roles of bacterial cytochrome c
      peroxidases.
AB  - Cytochrome-c peroxidases (CCPs) are a widespread family of enzymes that catalyse
      the conversion of hydrogen peroxide (H2O2) to water using haem co-factors. CCPs
      are found in both eukaryotes and prokaryotes, but the enzymes in each group use a
      distinct mechanism for catalysis. Eukaryotic CCPs contain a single b-type haem co
      factor. Conventional bacterial CCPs (bCCPs) are periplasmic enzymes that contain
      two covalently bound c-type haems. However, we have identified a sub-group of
      bCCPs by phylogenetic analysis that contains three haem-binding motifs. Although
      the structure and mechanism of several bacterial di-haem CCPs has been studied in
      detail and is well understood, the physiological role of these enzymes is often
      much less clear, especially in comparison to other peroxidatic enzymes such as
      catalase and alkyl-hydroperoxide reductase. In this review, the structure,
      mechanism and possible roles of bCCPs are examined in the context of their
      periplasmic location, the regulation of their synthesis by oxygen and their
      particular function in pathogens.

PMID- 17027372
TI  - Respiratory transformation of nitrous oxide (N2O) to dinitrogen by Bacteria and
      Archaea.
AB  - N2O is a potent greenhouse gas and stratospheric reactant that has been steadily
      on the rise since the beginning of industrialization. It is an obligatory
      inorganic metabolite of denitrifying bacteria, and some production of N2O is also
      found in nitrifying and methanotrophic bacteria. We focus this review on the
      respiratory aspect of N2O transformation catalysed by the multicopper enzyme
      nitrous oxide reductase (N2OR) that provides the bacterial cell with an electron
      sink for anaerobic growth. Two types of Cu centres discovered in N2OR were both
      novel structures among the Cu proteins: the mixed-valent dinuclear Cu(A) species
      at the electron entry site of the enzyme, and the tetranuclear Cu(Z) centre as
      the first catalytically active Cu-sulfur complex known. Several accessory
      proteins function as Cu chaperone and ABC transporter systems for the biogenesis
      of the catalytic centre. We describe here the paradigm of Z-type N2OR, whose
      characteristics have been studied in most detail in the genera Pseudomonas and
      Paracoccus. Sequenced bacterial genomes now provide an invaluable additional
      source of information. New strains harbouring nos genes and capability of N2O
      utilization are being uncovered. This reveals previously unknown relationships
      and allows pattern recognition and predictions. The core nos genes, nosZDFYL,
      share a common phylogeny. Most principal taxonomic lineages follow the same
      biochemical and genetic pattern and share the Z-type enzyme. A modified N2OR is
      found in Wolinella succinogenes, and circumstantial evidence also indicates for
      certain Archaea another type of N2OR. The current picture supports the view of
      evolution of N2O respiration prior to the separation of the domains Bacteria and
      Archaea. Lateral nos gene transfer from an epsilon-proteobacterium as donor is
      suggested for Magnetospirillum magnetotacticum and Dechloromonas aromatica. In a
      few cases, nos gene clusters are plasmid borne. Inorganic N2O metabolism is
      associated with a diversity of physiological traits and biochemically challenging
      metabolic modes or habitats, including halorespiration, diazotrophy, symbiosis,
      pathogenicity, psychrophily, thermophily, extreme halophily and the marine
      habitat down to the greatest depth. Components for N2O respiration cover
      topologically the periplasm and the inner and outer membranes. The Sec and Tat
      translocons share the task of exporting Nos components to their functional sites.
      Electron donation to N2OR follows pathways with modifications depending on the
      host organism. A short chronology of the field is also presented.

PMID- 17027373
TI  - A circadian timing mechanism in the cyanobacteria.
AB  - Cyanobacteria such as Synechococcus elongatus PCC 7942, Thermosynechococcus
      elongatus BP-1, and Synechocystis species strain PCC 6803 have an endogenous
      timing mechanism that can generate and maintain a 24 h (circadian) periodicity to
      global (whole genome) gene expression patterns. This rhythmicity extends to many
      other physiological functions, including chromosome compaction. These rhythmic
      patterns seem to reflect the periodicity of availability of the primary energy
      source for these photoautotrophic organisms, the Sun. Presumably, eons of
      environmentally derived rhythmicity--light/dark cycles--have simply been
      mechanistically incorporated into the regulatory networks of these cyanobacteria.
      Genetic and biochemical experimentation over the last 15 years has identified
      many key components of the primary timing mechanism that generates rhythmicity,
      the input pathways that synchronize endogenous rhythms to exogenous rhythms, and
      the output pathways that transduce temporal information from the timekeeper to
      the regulators of gene expression and function. Amazingly, the primary timing
      mechanism has evidently been extracted from S. elongatus PCC 7942 and can also
      keep time in vitro. Mixing the circadian clock proteins KaiA, KaiB, and KaiC from
      S. elongatus PCC 7942 in vitro and adding ATP results in a circadian rhythm in
      the KaiC protein phosphorylation state. Nonetheless, many questions still loom
      regarding how this circadian clock mechanism works, how it communicates with the
      environment and how it regulates temporal patterns of gene expression. Many
      details regarding structure and function of the individual clock-related proteins
      are provided here as a basis to discuss these questions. A strong, data-intensive
      foundation has been developed to support the working model for the cyanobacterial
      circadian regulatory system. The eventual addition to that model of the metabolic
      parameters participating in the command and control of this circadian global
      regulatory system will ultimately allow a fascinating look into whole-cell
      physiology and metabolism and the consequential organization of global gene
      expression patterns.

PMID- 17027376
TI  - Top-down facilitation of visual object recognition: object-based and context
      based contributions.
AB  - The neural mechanisms subserving visual recognition are traditionally described
      in terms of bottom-up analysis, whereby increasingly complex aspects of the
      visual input are processed along a hierarchical progression of cortical regions.
      However, the importance of top-down facilitation in successful recognition has
      been emphasized in recent models and research findings. Here we consider evidence
      for top-down facilitation of recognition that is triggered by early information
      about an object, as well as by contextual associations between an object and
      other objects with which it typically appears. The object-based mechanism is
      proposed to trigger top-down facilitation of visual recognition rapidly, using a
      partially analyzed version of the input image (i.e., a blurred image) that is
      projected from early visual areas directly to the prefrontal cortex (PFC). This
      coarse representation activates in the PFC information that is back-projected as
      "initial guesses" to the temporal cortex where it presensitizes the most likely
      interpretations of the input object. In addition to this object-based
      facilitation, a context-based mechanism is proposed to trigger top-down
      facilitation through contextual associations between objects in scenes. These
      contextual associations activate predictive information about which objects are
      likely to appear together, and can influence the "initial guesses" about an
      object's identity. We have shown that contextual associations are analyzed by a
      network that includes the parahippocampal cortex and the retrosplenial complex.
      The integrated proposal described here is that object- and context-based top-down
      influences operate together, promoting efficient recognition by framing early
      information about an object within the constraints provided by a lifetime of
      experience with contextual associations.

PMID- 17027377
TI  - Building the gist of a scene: the role of global image features in recognition.
AB  - Humans can recognize the gist of a novel image in a single glance, independent of
      its complexity. How is this remarkable feat accomplished? On the basis of
      behavioral and computational evidence, this paper describes a formal approach to
      the representation and the mechanism of scene gist understanding, based on scene
      centered, rather than object-centered primitives. We show that the structure of a
      scene image can be estimated by the mean of global image features, providing a
      statistical summary of the spatial layout properties (Spatial Envelope
      representation) of the scene. Global features are based on configurations of
      spatial scales and are estimated without invoking segmentation or grouping
      operations. The scene-centered approach is not an alternative to local image
      analysis but would serve as a feed-forward and parallel pathway of visual
      processing, able to quickly constrain local feature analysis and enhance object
      recognition in cluttered natural scenes.

PMID- 17027378
TI  - Beyond the face: exploring rapid influences of context on face processing.
AB  - Humans optimize behavior by deriving context-based expectations. Contextual data
      that are important for survival are extracted rapidly, using coarse information,
      adaptive decision strategies, and dedicated neural infrastructure. In the field
      of object perception, the influence of a surrounding context has been a major
      research theme, and it has generated a large literature. That visual context, as
      typically provided by natural scenes, facilitates object recognition as has been
      convincingly demonstrated (Bar, M. (2004) Nat. Rev. Neurosci., 5: 617-629). Just
      like objects, faces are generally encountered as part of a natural scene. Thus
      far, the facial expression literature has neglected such context and treats
      facial expressions as if they stand on their own. This constitutes a major gap in
      our knowledge. Facial expressions tend to appear in a context of head and body
      orientations, body movements, posture changes, and other object-related actions
      with a similar or at least a closely related meaning. For instance, one would
      expect a frightened face when confronted to an external danger to be at least
      accompanied by withdrawal movements of head and shoulders. Furthermore, some cues
      provided by the environment or the context in which a facial expression appears
      may have a direct relation with the emotion displayed by the face. The brain may
      even fill in the natural scene context typically associated with the facial
      expression. Recognition of the facial expression may also profit from processing
      the vocal emotion as well as the emotional body language that normally accompany
      it. Here we review the emerging evidence on how the immediate visual and auditory
      contexts influence the recognition of facial expressions.

PMID- 17027379
TI  - The effectiveness of disruptive coloration as a concealment strategy.
AB  - Our understanding of camouflage has been developing for over 100 years. Several
      underlying principles have emerged. Background pattern matching, or crypsis, is
      insufficient to conceal objects because of edge information. Other strategies
      exist to disrupt the continuity of extended edges. These strategies are reviewed.
      We pay particular attention to the theory of disruptive coloration, which
      predicts that high-contrast elements located at the object edge will mask the
      perception of a target as belonging to a certain category of object, in spite of
      the fact that the edge elements are independently visible. Although this strategy
      has long been assumed to be effective, there has been a lack of supportive data
      involving the perception of targets by nonhuman animals. We present evidence,
      from a field study, in support of the notion that disruptive coloration reduces
      the chances of bird predation of artificial "moths."

PMID- 17027381
TI  - From perceptive fields to Gestalt.
AB  - Studies on visual psychophysics and perception conducted in the Freiburg
      psychophysics laboratory during the last 35 years are reviewed. Many of these
      were inspired by single-cell neurophysiology in cat and monkey. The aim was to
      correlate perceptual phenomena and their effects to possible neuronal mechanisms
      from retina to visual cortex and beyond. Topics discussed include perceptive
      field organization, figure-ground segregation and grouping, fading and filling
      in, and long-range color interaction. While some of these studies succeeded in
      linking perception to neuronal response patterns, others require further
      investigation. The task of probing the human brain with perceptual phenomena
      continues to be a challenge for the future.

PMID- 17027382
TI  - In honour of Lothar Spillmann - filling-in, wiggly lines, adaptation, and
      aftereffects.
AB  - I have studied a number of visual phenomena that Lothar Spillmann has already
      elucidated. These include: Neon spreading: when a small red cross is superimposed
      on intersecting black lines, the red cross seems to spread out into an illusory
      disk. Unlike the Hermann grid, neon spreading is relatively unaffected when the
      black lines are curved or wiggly. This suggests that the Hermann grid, but not
      neon spreading, involves long-range interactions. Neon spreading can be shown in
      random-dot patterns, even without intersections. It is strongest when the red
      crosses are equiluminous with the gray background. Adaptation, aftereffects, and
      filling-in: direct and induced aftereffects of color, motion, and dimming.
      Artificial scotomata and filling-in: the "dam" theory is false. Staring at wiggly
      lines or irregularly scattered dots makes them gradually appear straighter, or
      more regularly spaced. I present evidence that irregularity is actually a visual
      dimension to which the visual system can adapt. Conjectures on the nature of
      peripheral fading and of motion-induced blindness. Some failed experiments on
      correlated visual inputs and cortical plasticity.

PMID- 17027383
TI  - Lightness, filling-in, and the fundamental role of context in visual perception.
AB  - Visual perception is defined by the unique spatial interactions that distinguish
      it from the point-to-point precision of a photometer. Over several decades,
      Lothar Spillmann has made key observations about the nature of these interactions
      and the role of context in perception. Our lab has explored the perceptual
      properties of spatial interactions and more generally the importance of visual
      context for neuronal responses and perception. Our investigations into the
      spatiotemporal dynamics of lightness provide insight into underlying mechanisms.
      For example, backward masking and luminance modulation experiments suggest that
      the representation of a uniformly luminous object develops first at the borders
      and, in some manner, the center fills in. The temporal dynamics of lightness
      induction are also consistent with a filling-in process. There is a slow cutoff
      temporal frequency above which surround luminance modulation will not elicit
      perceptual induction of a central area. The larger the central area, the lower
      the cutoff frequency for induction, perhaps indicating that an edge-based process
      requires more time to "complete" the larger area. In recordings from primary
      visual cortex we find that neurons respond in a manner surprisingly consistent
      with lightness perception and the spatial and temporal properties of induction.
      For example, the activity of V1 neurons can be modulated by light outside the
      receptive field and as the modulation rate is increased response modulation falls
      off more rapidly for large uniform areas than smaller areas. The conclusion we
      draw from these experiments is that lightness appears to be computed slowly on
      the basis of edge and context information. A possible role for the spatial
      interactions is lightness constancy, which is thought to depend on extensive
      spatial integration. We find not only that V1 responses are strongly context
      dependent, but that this dependence makes V1 lightness constant on average. The
      dependence of constancy on surround interactions underscores the fundamental role
      that context plays in perception. In more recent studies, further support has
      been found for the importance of context in experiments using natural scene
      stimuli.

PMID- 17027384
TI  - Beyond a relay nucleus: neuroimaging views on the human LGN.
AB  - The lateral geniculate nucleus (LGN) is the thalamic station in the
      retinocortical projection and has traditionally been viewed as the gateway for
      sensory information to enter the cortex. Here, we review recent studies of the
      human LGN that have investigated the retinotopic organization, physiologic
      response properties, and modulation of neural activity by selective attention and
      by visual awareness in a binocular rivalry paradigm. In the retinotopy studies,
      we found that the contralateral visual field was represented with the lower field
      in the medial-superior portion and the upper field in the lateral-inferior
      portion of each LGN. The fovea was represented in posterior and superior
      portions, with increasing eccentricities represented more anteriorly. Functional
      MRI responses increased monotonically with stimulus contrast in the LGN and in
      visual cortical areas. In the LGN, the dynamic response range of the contrast
      function was larger and contrast gain was lower than in the cortex. In our
      attention studies, we found that directed attention to a spatial location
      modulated neural activity in the LGN in several ways: it enhanced neural
      responses to attended stimuli, attenuated responses to ignored stimuli, and
      increased baseline activity in the absence of visual stimulation. Furthermore, we
      showed in a binocular rivalry paradigm that neural activity in the LGN correlated
      strongly with the subjects' reported percepts. The overall view that emerges from
      these studies is that the human LGN plays a role in perception and cognition far
      beyond that of a relay nucleus and, rather, needs to be considered as an early
      gatekeeper in the control of visual attention and awareness.

PMID- 17027386
TI  - Finding a face in the crowd: parallel and serial neural mechanisms of visual
      selection.
AB  - At any given moment, our visual system is confronted with more information than
      it can process. Thus, attention is needed to select behaviorally relevant
      information in a visual scene for further processing. Behavioral studies of
      attention during visual search have led to the distinction between serial and
      parallel mechanisms of selection. To find a target object in a crowded scene, for
      example a "face in a crowd", the visual system might turn on and off the neural
      representation of each object in a serial fashion, testing each representation
      against a template of the target object. Alternatively, it might allow the
      processing of all objects in parallel, but bias activity in favor of those
      neurons representing critical features of the target, until the target emerges
      from the background. Recent neurophysiological evidence shows that both serial
      and parallel selections take place in neurons of the ventral "object-recognition
      pathway" during visual search tasks in which monkeys freely scan complex displays
      to find a target object. Furthermore, attentional selection appears to be
      mediated by changes in the synchrony of responses of neuronal populations in
      addition to the modulation of the firing rate of individual neurons.

PMID- 17027387
TI  - Saccades, salience and attention: the role of the lateral intraparietal area in
      visual behavior.
AB  - Neural activity in the lateral intraparietal area (LIP) has been associated with
      attention to a location in visual space, and with the intention to make saccadic
      eye movement. In this study we show that neurons in LIP respond to recently
      flashed task-irrelevant stimuli and saccade targets brought into the receptive
      field by a saccade, although they respond much to the same stimuli when they are
      stable in the environment. LIP neurons respond to the appearance of a flashed
      distractor even when a monkey is planning a memory-guided delayed saccade
      elsewhere. We then show that a monkey's attention, as defined by an increase in
      contrast sensitivity, is pinned to the goal of a memory-guided saccade throughout
      the delay period, unless a distractor appears, in which case attention
      transiently moves to the site of the distractor and then returns to the goal of
      the saccade. LIP neurons respond to both the saccade goal and the distractor, and
      this activity correlates with the monkey's locus of attention. In particular, the
      activity of LIP neurons predicts when attention migrates from the distractor back
      to the saccade goal. We suggest that the activity in LIP provides a salience map
      that is interpreted by the oculomotor system as a saccade goal when a saccade is
      appropriate, and simultaneously is used by the visual system to determine the
      locus of attention.

PMID- 17027388
TI  - Visual masking approaches to visual awareness.
AB  - In visual masking, visible targets are rendered invisible by modifying the
      context in which they are presented, but not by modifying the targets themselves.
      Here I summarize a decade of experimentation using visual masking illusions in
      which my colleagues and I have begun to establish the minimal set of conditions
      necessary to maintain the awareness of the visibility of simple unattended
      stimuli. We have established that spatiotemporal edges must be present for
      targets to be visible. These spatiotemporal edges must be encoded by transient
      bursts of spikes in the early visual system. If these bursts are inhibited,
      visibility fails. Target-correlated activity must rise within the visual
      hierarchy at least to the level of V3, and be processed within the occipital
      lobe, to achieve visibility. The specific circuits that maintain visibility are
      not yet known, but we have deduced that lateral inhibition plays a critical role
      in sculpting our perception of visibility, both by causing interactions between
      stimuli positioned across space, and also by shaping the responses to stimuli
      across time. Further, the studies have served to narrow the number of possible
      theories to explain visibility and visual masking. Finally, we have discovered
      that lateral inhibition builds iteratively in strength throughout the visual
      hierarchy, for both monoptic and dichoptic stimuli. Since binocular information
      is not integrated until inputs from the two eyes reach the primary visual cortex,
      it follows that the early visual areas contain differential levels of monoptic
      and dichoptic lateral inhibitions. We exploited this fact to discover that
      excitatory integration of binocular inputs occurs at an earlier level than
      interocular suppression. These findings are potentially fundamental to our
      understanding of all forms of binocular vision and to determining the role of
      binocular rivalry in visual awareness.

PMID- 17027389
TI  - Blindsight, conscious vision, and the role of primary visual cortex.
AB  - What is the role the primary visual cortex (V1) in vision? Is it necessary for
      conscious sight, as indicated by the cortical blindness that results from V1
      destruction? Is it even necessary for blindsight, the nonreflexive visual
      functions that can be evoked with stimuli presented to cortically blind fields?
      In the context of this controversial issue, I present evidence indicating that
      not only is blindsight possible, but that conscious vision may, to a varying
      degree, return to formerly blind fields with time and practice even in cases
      where functional neuroimaging reveals no V1 activation.

PMID- 17027390
TI  - Chapter 13 Bilateral frontal leucotomy does not alter perceptual alternation
      during binocular rivalry.
AB  - When discrepant stimuli are presented to each eye and fusion is impossible,
      perception spontaneously oscillates between the two patterns (binocular rivalry).
      Functional MRI (fMRI) research identified a frontoparietal network in the right
      hemisphere associated with perceptual transitions, and it has been proposed that
      this network is at the origin of the perceptual alternations. Neuroimaging
      results, however, do not imply causality and lesion studies are needed. Here, we
      studied one patient who had most of the prefrontal cortex disconnected from the
      rest of the brain after a bilateral frontal leucotomy. His performance in two
      binocular rivalry tasks was indistinguishable from that of the controls. The
      results indicate that prefrontal cortex is unnecessary for perceptual
      alternations during binocular rivalry.

PMID- 17027392
TI  - Combining visual and auditory information.
AB  - Robust perception requires that information from by our five different senses be
      combined at some central level to produce a single unified percept of the world.
      Recent theory and evidence from many laboratories suggests that the combination
      does not occur in a rigid, hardwired fashion, but follows flexible situation
      dependent rules that allow information to be combined with maximal efficiency. In
      this review we discuss recent evidence from our laboratories investigating how
      information from auditory and visual modalities is combined. The results support
      the notion of Bayesian combination. We also examine temporal alignment of
      auditory and visual signals, and show that perceived simultaneity does not depend
      solely on neural latencies, but involves active processes that compensate, for
      example, for the physical delay introduced by the relatively slow speed of sound.
      Finally, we go on to show that although visual and auditory information is
      combined to maximize efficiency, attentional resources for the two modalities are
      largely independent.

PMID- 17027393
TI  - Crossmodal interactions: lessons from synesthesia.
AB  - Synesthesia is a condition in which stimulation in one modality also gives rise
      to a perceptual experience in a second modality. In two recent studies we found
      that the condition is more common than previously reported; up to 5% of the
      population may experience at least one type of synesthesia. Although the
      condition has been traditionally viewed as an anomaly (e.g., breakdown in
      modularity), it seems that at least some of the mechanisms underlying synesthesia
      do reflect universal crossmodal mechanisms. We review here a number of examples
      of crossmodal correspondences found in both synesthetes and nonsynesthetes
      including pitch-lightness and vision-touch interaction, as well as cross-domain
      spatial-numeric interactions. Additionally, we discuss the common role of spatial
      attention in binding shape and color surface features (whether ordinary or
      synesthetic color). Consistently with behavioral and neuroimaging data showing
      that chromatic-graphemic (colored-letter) synesthesia is a genuine perceptual
      phenomenon implicating extrastriate cortex, we also present electrophysiological
      data showing modulation of visual evoked potentials by synesthetic color
      congruency.

PMID- 17027394
TI  - Integrating motion information across sensory modalities: the role of top-down
      factors.
AB  - Recent studies have highlighted the influence of multisensory integration
      mechanisms in the processing of motion information. One central issue in this
      research area concerns the extent to which the behavioral correlates of these
      effects can be attributed to late post-perceptual (i.e., response-related or
      decisional) processes rather than to perceptual mechanisms of multisensory
      binding. We investigated the influence of various top-down factors on the
      phenomenon of crossmodal dynamic capture, whereby the direction of motion in one
      sensory modality (audition) is strongly influenced by motion presented in another
      sensory modality (vision). In Experiment 1, we introduced extensive feedback in
      order to manipulate the motivation level of participants and the extent of their
      practice with the task. In Experiment 2, we reduced the variability of the
      irrelevant (visual) distractor stimulus by making its direction predictable
      beforehand. In Experiment 3, we investigated the effects of changing the stimulus
      response mapping (task). None of these manipulations exerted any noticeable
      influence on the overall pattern of crossmodal dynamic capture that was observed.
      We therefore conclude that the integration of multisensory motion cues is robust
      to a number of top-down influences, thereby revealing that the crossmodal dynamic
      capture effect reflects the relatively automatic integration of multisensory
      motion information.

PMID- 17027395
TI  - Crossmodal audio-visual interactions in the primary visual cortex of the visually
      deprived cat: a physiological and anatomical study.
AB  - Blind individuals often demonstrate enhanced non-visual perceptual abilities.
      Neuroimaging and transcranial magnetic stimulation experiments have suggested
      that computations carried out in the occipital cortex may underlie these enhanced
      somatosensory or auditory performances. Thus, cortical areas that are dedicated
      to the analysis of the visual scene may, in the blind, acquire the capacity to
      participate in other sensory processing. However, the neural substrate that
      underlies this transfer of function is not fully characterized. Here we studied
      the synaptic and anatomical basis of this phenomenon in cats that were visually
      deprived by dark rearing, either early visually deprived after birth (EVD), or
      late visually deprived after the end of the critical period (LVD); data were
      compared with those obtained in normally reared cats (controls). The presence of
      synaptic and spike responses to auditory stimulation was examined by means of
      intracellular recordings in area 17 and the border between areas 17 and 18. While
      none of the cells recorded in control and LVD cats showed responses to sound, 14%
      of the cells recorded in EVD cats showed both subthreshold synaptic responses and
      suprathreshold spike responses to auditory stimuli. Synaptic responses were of
      small amplitude, but well time-locked to the stimuli and had an average latency
      of 30+/-12ms. In an attempt to identify the origin of the inputs carrying
      auditory information to the visual cortex, wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling
      examined in the cortex and thalamus. No significant retrograde labeling was found
      in auditory cortical areas. However, the proportion of neurons projecting from
      supragranular layers of the posteromedial and posterolateral parts of the lateral
      suprasylvian region to V1 was higher than that in control cats. Retrograde
      labeling in the lateral geniculate nucleus showed no difference in the total
      number of neurons between control and visually deprived cats, but there was a
      higher proportion of labeling in C-laminae in deprived cats. Labeled cells were
      not found in the medial geniculate nucleus, a thalamic relay for auditory
      information, in either control or visually deprived cats. Finally,
      immunohistochemistry of the visual cortex of deprived cats revealed a striking
      decrease in pavalbumin- and calretinin-positive neurons, the functional
      implications of which we discuss.

PMID- 17027396
TI  - The "other" transformation required for visual-auditory integration:
      representational format.
AB  - Multisensory integration of spatial signals requires not only that stimulus
      locations be encoded in the same spatial reference frame, but also that stimulus
      locations be encoded in the same representational format. Previous studies have
      addressed the issue of spatial reference frame, but representational format,
      particularly for sound location, has been relatively overlooked. We discuss here
      our recent findings that sound location in the primate inferior colliculus is
      encoded using a "rate" code, a format that differs from the place code used for
      representing visual stimulus locations. Possible mechanisms for transforming
      signals from rate-to-place or place-to-rate coding formats are considered.

PMID- 17027398
TI  - Publication bias.

PMID- 17027399
TI  - Sensitivity of routine 1.0-Tesla magnetic resonance imaging versus arthroscopy as
      gold standard in fresh traumatic chondral lesions of the knee in young adults.
AB  - PURPOSE: The purpose of this study was to evaluate the sensitivity, specificity,
      and accuracy of routine 1.0-Tesla magnetic resonance imaging (MRI) versus
      arthroscopy in detecting fresh traumatic chondral lesions of the knee. METHODS:
      Over a period of 6 years, 578 consecutive military personnel underwent MRI before
      arthroscopy of the knee. Of these, 32 patients with arthroscopically proven fresh
      traumatic chondral lesions of the knee were chosen for further analysis. A
      supplementary condition was that arthroscopy was performed no later than 6 weeks
      after the onset of trauma. The original MRIs and hospital records were re
      evaluated and the chondral lesions were graded and compared with arthroscopic
      findings. The arthroscopic results served as the gold standard when the
      sensitivity, specificity, and accuracy of MRI were calculated. RESULTS: The age
      of the patients ranged from 19 to 21 years (mean, 19.6 years). MRI detected
      cartilage defects with a sensitivity of 36% (95% confidence interval [CI], 23% to
      50%), specificity of 91% (95% CI, 85% to 95%), and diagnostic accuracy of 78%
      (95% CI, 72% to 83%). MRI results were affected by the grade of the chondral
      lesions. CONCLUSIONS: This study shows that routine 1.0-T MRI is not sensitive
      but is specific and somewhat accurate in detecting fresh traumatic articular
      cartilage lesions. The hypothesis of this study was that 1.0-T MRI could replace
      diagnostic arthroscopy in the diagnosis of fresh traumatic chondral lesions. Our
      results fail to support this hypothesis because of the poor sensitivity obtained
      with MRI. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria.

PMID- 17027400
TI  - Initial biomechanical properties of staple-anchor Achilles tendon allograft and
      interference screw bone-patellar tendon-bone autograft fixation for anterior
      cruciate ligament reconstruction in a cadaveric model.
AB  - PURPOSE: Anterior cruciate ligament (ACL) reconstruction is a common procedure
      that has a fairly high success rate. Despite such success, controversy exists
      with regard to fixation and graft type. The purpose of this study was to quantify
      the maximum load to failure for staple-anchor freeze-dried Achilles tendon
      allograft fixation compared with interference screw bone-pattelar tendon-bone
      autograft fixation at the time of insertion for ACL reconstruction. METHODS:
      Eleven pairs of cadaveric knees were prepared for ACL reconstruction by
      disarticulation before graft insertion. The tibia and femur were mounted
      separately onto an MTS machine and were loaded to failure in line with the
      tunnels. Femoral fixation for the allograft was provided by a staple anchor;
      tibial fixation was provided by a suture anchor. Titanium interference screws on
      the femoral and tibial sides provided autograft fixation. A paired t test was
      performed to compare mechanical testing results in the 2 groups. RESULTS: Mean
      maximum load to failure for the allograft was 58.7 N (range, 32.3 to 92.6 N) and
      119.6 N (range, 82 to 165.9 N) for the femur and the tibia, respectively,
      compared with 228.2 N (range, 74.2 to 352 N) and 232.9 N (range, 65.1 to 553.1 N)
      for the autografts. This difference was statistically significant (P < .001) for
      femoral fixation, but it was not statistically significant for tibial fixation (P
      = .186). CONCLUSIONS: Soft tissue Achilles tendon allograft with staple fixation
      is a significantly weaker fixation construct when compared with autograft bone
      patellar tendon-bone with interference screw fixation. CLINICAL RELEVANCE: This
      study shows significantly weaker fixation in the staple-alograft construct and
      yet this construct has had at least equivalent results over a 5-year time frame,
      indicating that rigid femoral fixation may not be a critical factor in long-term
      results.

PMID- 17027401
TI  - Assessment of reprocessed arthroscopic shaver blades.
AB  - PURPOSE: The purpose of this study was to evaluate the level of contaminants on,
      as well as the quality of, reprocessed shaver blades. METHODS: We assessed 7 new
      shaver blades and 27 shaver blades that had been reprocessed with mechanical
      cleaning, functional testing, and sterilization with ethylene oxide. A
      spectrophotometer measured the amount of nucleic acid and protein. The blade
      quality was assessed by photographing the blades with magnification and
      determining the percentage of damage present on each blade. A subset of shaver
      blades were then used to cut meniscal tissue, and the cut surface was measured
      for smoothness by image processing and automated laser scanning cytometry. In
      evaluation of the meniscus, for the subset of shavers, an image processing value
      of 1 indicates a smooth, straight line, and values lower than 1 reflect
      deviations in the cut surface (the closer the value is to 1, the smoother the
      surface). Laser scanning cytometry values indicate the percentage of
      irregularities in the cut surface (the lower the value is, the smoother the
      surface). RESULTS: Of the 27 reprocessed shaver blades, 13 (48%) had detectable
      levels of protein and 17 (63%) had detectable levels of nucleic acid. On the
      reprocessed shaver blades, protein levels ranged from 2.43 microg to 60 microg
      and nucleic acid levels ranged from 0.40 microg to 3.5 microg. No new shaver
      blade had contaminants. Twenty reprocessed shaver blades had been manufactured
      with teeth and could be evaluated for visible damage. Of these, 10 had 1% to 25%
      damage, 5 had 26% to 50% damage, 3 had 51% to 75% damage, and 2 had 76% to 100%
      damage. The new blades had no visible damage. Image processing revealed
      smoothness of the surface cut with new shaver blades, yielding values of 1 +/-
      0.12, whereas the values for reprocessed shaver blades ranged from 0.62 +/- 0.02
      to 1 +/- 0.07. Laser scanning cytometry values ranged from 3.3% to 7.1% for the
      new blades as compared with 5.8% to 20.0% for the reprocessed blades.
      CONCLUSIONS: Of the reprocessed shaver blades, 48% had detectable levels of
      protein and 63% had detectable levels of nucleic acid. All of the reprocessed
      blades visually evaluated showed some level of damage or wear, whereas no new
      blade had such damage. In addition, menisci cut with reprocessed shavers showed
      rougher edges than did menisci cut with new shavers. CLINICAL RELEVANCE: To make
      an informed decision regarding the use of reprocessed shaver blades, surgeons
      will want to know the level of contamination on, and the quality of, reprocessed
      shaver blades.

PMID- 17027402
TI  - Self-reported patient outcomes at a minimum of 5 years after allograft anterior
      cruciate ligament reconstruction with or without medial meniscus transplantation:
      an age-, sex-, and activity level-matched comparison in patients aged
      approximately 50 years.
AB  - PURPOSE: Patient outcomes at a minimum of 5 years after medial meniscus
      transplantation and primary anterior cruciate ligament (ACL) reconstruction via
      allograft tissues were compared with those of age-, sex-, and activity level
      matched patients who underwent meniscal repair or partial meniscectomy and
      primary ACL reconstruction via allograft tissues. METHODS: Eight patients (mean
      age, 51 +/- 5 years; three women and five men) at 5.5 +/- 0.5 years after medial
      meniscus transplantation and ACL reconstruction (group 1) and eight matched
      patients (mean age, 50 +/- 5 years; three women and five men) at 5.1 +/- 0.5
      years after meniscal repair or partial meniscectomy and ACL reconstruction (group
      2) completed the meniscus allograft clinical registry questionnaire, which
      combined the modified Lysholm knee scoring scale, the 1999 International Knee
      Documentation Committee subjective knee evaluation, and the knee pain level score
      on a 10-cm visual analog scale. RESULTS: Both groups displayed similar
      improvements in the modified Lysholm knee scoring scale components of pain, knee
      stability, squatting, stair climbing, and limping, as well as overall score (P <
      .05). Only group 2 displayed significant reductions in swelling. The groups
      displayed similar improvements in the 1999 International Knee Documentation
      Committee subjective knee evaluation components of sitting, rising from a chair,
      running, jumping, and stopping quickly, as well as overall score (P < .05). They
      also displayed significant improvements in the visual analog scale knee pain
      level score; however, group 1, which displayed greater preoperative pain levels,
      had considerably larger reductions. Most group 1 patients (7/8 [87.5%]) and all
      group 2 patients (8/8 [100%]) considered their surgery to be a success and would
      undergo the same procedure again if necessary. CONCLUSIONS: Although group 1 had
      greater preoperative knee pain levels, their pain levels at 5 years
      postoperatively were comparable to those in group 2. With the exception of
      swelling, comparable improvements were observed between groups for all other
      variables. LEVEL OF EVIDENCE: Level III, retrospective, case-control study.

PMID- 17027403
TI  - Sutures and suture anchors--update 2006.
AB  - PURPOSE: To evaluate recently introduced sutures and suture anchors for single
      pull load to failure strength and failure mode. METHODS: Suture anchors were
      tested in fresh porcine metaphyseal cortex and cancellous troughs with the use of
      an established protocol. An Instron machine applied tensile loads parallel to the
      axis of insertion at a rate of 12.5 mm/sec until failure, and mean anchor failure
      strengths were calculated. The mode of failure (anchor pull-out, suture eyelet
      cut-out, or suture failure) was recorded. Anchors tested included the BioRaptor
      2.9, BioZip, Super Revo, Impact, Allograft cortical anchor, SpiraLok, Herculon,
      AxyaLoop titanium anchors 3, 5, and 6.5 mm, AxyaLoop bioabsorbable anchors 3, 5,
      and 6.5, ParaFix titanium anchors 3, 5, and 6.5, ParaSorb BioAnchors 3, 5.5, and
      6.5, and Bio-Corkscrew FT. Sutures were also tested through an established
      protocol for load to failure. Sutures tested consisted of Orthocord, Ultrabraid
      (White and CoBraid), ForceFiber, Hi-Fi, MagnumWire, and Maxbraid Polyethylene
      Plus. RESULTS: Mean failure loads were as follows: BioRaptor 238 N, BioZip 366 N,
      double-loaded Super Revo 486 N, triple-loaded Super Revo 362 N, Impact 202 N,
      Allograft cortical anchor 240 N, SpiraLok 289 N, Herculon 819 N, AxyaLoop
      titanium anchors 3.0 (335 N), 5.0 (485 N), and 6.5 mm (465 N), AxyaLoop
      bioabsorbable anchors 3 (143 N), 5 (395 N), and 6.5 (369 N), ParaFix titanium
      anchors 3 (335 N), 5 (485 N), and 6.5 (465 N), ParaSorb BioAnchors 3 (143 N), 5.5
      (395 N), and 6.5 (369 N), and Bio-Corkscrew FT (260 N). The sutures all broke at
      the mid point of their tested strands away from the grips. Mean suture strength
      for No. 2 Orthocord was 92 N; for No. 2 Ultrabraid CoBraid and White, strengths
      were 265 N and 280 N, respectively; strength for No. 2 Force Fiber was 289 N, for
      No. 2 Hi-Fi 250 N, for No. 2 MagnumWire 303 N, and for No. 2 Maxbraid
      Polyethylene Plus 256 N. CONCLUSIONS: Newer suture products showed significant
      improvements in load to failure values when compared with braided polyester
      sutures. Higher load to failure values continue to be seen in metal versus
      biodegradable anchors and in screw-type versus nonscrew designs. CLINICAL
      RELEVANCE: Surgeons who prefer stronger sutures now have several high-strength
      suture options from which to choose. Most of the new anchors tested performed
      very well.

PMID- 17027404
TI  - Evaluation of residual rotator cuff defects after in vivo single- versus double
      row rotator cuff repairs.
AB  - PURPOSE: As arthroscopic rotator cuff surgery has advanced, new techniques have
      emerged to maximize the biomechanical strength of the repair construct. The
      double-row repair has been recommended as a means of increasing the contact area
      of the repaired rotator cuff to the native bone bed. This study attempts to
      sequentially examine and measure the rotator cuff footprint (in vivo) before cuff
      repair, after an initial lateral-row repair (before the medial-row sutures are
      tied), and finally, after the double-row repair. In this way, the rotator cuff
      footprint of single- and double-row repairs can be quantified and compared.
      METHODS: Between October 2004 and February 2005, 26 patients were enrolled in the
      study. These patients had rotator cuff tears that were amenable to double-row
      repair by means of performing the lateral-row repair before the medial-row
      repair. After preparation of the greater tuberosity footprint, the native
      footprint was measured in the medial-to-lateral direction. Next, the medial-row
      anchors and sutures were passed through the cuff (but not tied), and then the
      lateral row was secured via suture anchors and the arthroscope was reinserted
      into the intra-articular space. A depth gauge was introduced through the repaired
      cuff (lateral row only), and the residual bare footprint was measured. The medial
      row was then tied, and the cuff was again visualized from the intra-articular
      position to measure any remaining bare footprint. RESULTS: The mean footprint
      measured 17.0 +/- 1.9 mm from medial to lateral. After repair of the lateral row,
      the mean residual uncovered footprint measured 9.0 +/- 2.0 mm. This constituted a
      52.7% +/- 9.2% uncovered area after a single lateral-row repair. After the medial
      row was secured, there were no remaining residual deficits of the cuff footprint.
      CONCLUSIONS: After an isolated lateral-row repair, 52.7% +/- 9.2% of the rotator
      cuff footprint remains uncovered. On average, the double-row repair offered over
      twice the footprint coverage yielded by a single-row repair. CLINICAL RELEVANCE:
      The arthroscopic shoulder surgeon should be aware of the enhanced footprint
      coverage offered by double-row rotator cuff fixation as opposed to single-row
      rotator cuff fixation.

PMID- 17027405
TI  - The bear-hug test: a new and sensitive test for diagnosing a subscapularis tear.
AB  - PURPOSE: It was our intent to devise a new clinical test that would more
      accurately diagnose subscapularis tears than the current clinical tests. This new
      test is called the bear-hug test. The purpose of this study was to assess the
      bear-hug test and compare it with the current tests of subscapularis function
      (lift-off, belly-press, and Napoleon tests). METHODS: Between January 2004 and
      March 2004, 68 consecutive patients scheduled for an arthroscopic procedure were
      evaluated preoperatively; the preoperative clinical examination findings were
      then correlated with arthroscopic findings. Lift-off, belly-press, Napoleon, and
      bear-hug tests were included in the examination. Furthermore, for the belly-press
      and bear-hug tests, the strength was precisely quantified by means of an
      electronic digital tensiometer (Kern HBC). Diagnostic arthroscopy was the
      reference that determined the actual pathologic lesions. RESULTS: Subscapularis
      tears occurred with a prevalence rate of 29.4%. Of the subscapularis tears, 40%
      were not predicted by preoperative assessment by use of all of the tests. The
      bear-hug test was found to be the most sensitive test (60%) of all of those
      studied (belly-press test, 40%; Napoleon test, 25%; and lift-off test, 17.6%). In
      contrast, all 4 tests had a high specificity (lift-off test, 100%; Napoleon test,
      97.9%; belly-press test, 97.9%; and bear-hug test, 91.7%). No statistically
      significant difference was found between the area under the receiver operating
      characteristic curve of the bear-hug test and that of the belly-press test in
      diagnosing a torn subscapularis. However, the areas under the receiver operating
      characteristic curve for both the bear-hug test and the belly-press test were
      significantly greater than those for the lift-off and Napoleon tests (P < .05).
      Positive bear-hug and belly-press tests suggest a tear of at least 30% of the
      subscapularis, whereas a positive Napoleon test indicates that greater than 50%
      of the subscapularis is torn. Furthermore, a positive lift-off test is not found
      until at least 75% of the subscapularis is torn. CONCLUSIONS: The bear-hug test
      optimizes the chance of detecting a tear of the upper part of the subscapularis
      tendon. Moreover, because the bear-hug test represents the most sensitive test,
      it can be considered to be the most likely clinical test to alert the surgeon to
      a possible subscapularis tear. Performing all of the subscapularis tests is
      useful in predicting the size of the tear. LEVEL OF EVIDENCE: Level I, diagnostic
      study: testing of previously developed criteria in a series of consecutive
      patients with arthroscopy used as the criterion standard.

PMID- 17027406
TI  - Osteochondral lesions of the talus: randomized controlled trial comparing
      chondroplasty, microfracture, and osteochondral autograft transplantation.
AB  - PURPOSE: The purpose of this study was to compare outcomes of chondroplasty
      versus microfracture versus osteochondral autologous transplantation (OAT) in
      patients with osteochondral lesions of the talus (OLT). METHODS: After
      prospective sample size analysis, patients with symptomatic, recalcitrant Ferkel
      class 2b, 3, and 4 OLT were randomized to chondroplasty, microfracture, or OAT
      treatment groups. Outcomes were measured with use of the American Orthopaedic
      Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHS), the Subjective
      Assessment Numeric Evaluation (SANE) rating, Numeric Pain Intensity (NPI), and
      magnetic resonance imaging (MRI). RESULTS: Eleven patients had chondroplasty, 10
      ankles (9 patients) had microfracture, and 12 patients had OAT. Mean time to
      follow-up was 53 months (range, 24 to 119 months). AHS scores showed no
      differences at 12 and 24 months, and SANE ratings showed no differences at final
      follow-up. NPI was significantly lower (P < .001) in chondroplasty and
      microfracture cases as compared with OAT at 24 hours postoperatively. Pearson's
      correlation analysis demonstrated an inverse relation between microfracture and
      OAT groups in that better outcome was associated with smaller lesions, compared
      with the chondroplasty group, which revealed mixed results with no particular
      trend. MRI revealed incomplete fill and edema after chondroplasty or
      microfracture and chondral gaps after OAT. CONCLUSION: Our results demonstrate no
      difference between chondroplasty, microfracture, and OAT with regard to AHS and
      SANE ratings in patients with OLT. However, NPI at 24 hours postoperatively was
      significantly lower in patients who had chondroplasty and microfracture. LEVEL OF
      EVIDENCE: Level I, Therapeutic study, high-quality randomized controlled trial
      with no statistically significant differences but narrow confidence interval.

PMID- 17027407
TI  - A retrospective review of bone tunnel enlargement after anterior cruciate
      ligament reconstruction with hamstring tendons fixed with a metal round
      cannulated interference screw in the femur.
AB  - PURPOSE: To assess bone tunnel enlargement after anterior cruciate ligament (ACL)
      reconstruction with the use of hamstring tendons fixed with a round cannulated
      interference (RCI) screw in the femur. METHODS: A consecutive series of 30 ACL
      reconstructions performed with hamstring tendons fixed with an RCI screw in the
      femur and with staples via Leeds-Keio ligament in the tibia was retrospectively
      reviewed. The clinical outcome was evaluated through the Lysholm score. Anterior
      instability was tested by Telos-SE (Telos Japan, Tokyo, Japan) measurement. The
      location and angle of each femoral and tibial tunnel were measured with the use
      of plain radiographs, and bone tunnel enlargement greater than 2 mm detected any
      time 3, 6, 12, and 24 months postoperatively was defined as positive. Each factor
      (location and angle of the tunnels, sex, affected side, age, Lysholm score, and
      Telos-SE measurement) was compared between enlarged and nonenlarged groups.
      RESULTS: Positive enlargement of the bone tunnel (>2.0 mm) was observed in 36.7%
      (11 of 30) on the femoral side and 33.3% (10 of 30) on the tibial side, and in 6
      knees of both sides. Half of patients (15 of 30) had an enlarged tunnel on the
      femoral or the tibial side until 1 year postoperatively. In most cases,
      enlargement reached maximum at 6 months postoperatively. Female patients tended
      to have an enlarged tunnel, especially on the femoral side (P < .05). Tunnel
      enlargement was not correlated with location and angle of the tunnels. Moreover,
      no difference was found in Lysholm score and Telos-SE measurement between
      enlarged and nonenlarged groups, although the nonenlarged group tended to exhibit
      higher Lysholm score and lesser instability. CONCLUSIONS: Bone tunnel enlargement
      of the femoral or tibial side was observed in half of patients (6 in both sides,
      5 only in the femur, and 4 only in the tibia) after ACL reconstruction was
      performed with a hamstring tendon fixed with an RCI screw. Female patients had a
      greater chance for enlargement of the femoral tunnel than did males. This
      enlargement had no significant impact on patient activity and on anterior
      instability of the knee 1 year after surgery. LEVEL OF EVIDENCE: Level IV,
      Therapeutic case series.

PMID- 17027408
TI  - Changes in knee laxity and ligament force after sectioning the posteromedial
      bundle of the posterior cruciate ligament.
AB  - PURPOSE: Our purpose was to evaluate the role of the posteromedial (PM) bundle of
      the native posterior cruciate ligament (PCL) in restraining posterior tibial
      translation and the effects of sectioning of the PM bundle on PCL forces.
      METHODS: The PCL's femoral origin was mechanically isolated by use of a
      cylindrical coring cutter, and a cap of bone containing the ligament fibers was
      attached to a load cell that recorded resultant force in the ligament as the knee
      was passively extended from 120 degrees to 0 degrees without and with simulated
      tibial loading conditions. Anteroposterior laxity was also measured after load
      cell installation. The PM bundle was cut at its femoral origin, and all tests
      were repeated. RESULTS: Cutting the PM bundle produced small but statistically
      significant increases in mean laxity at 0 degrees (+1.06 mm) and 10 degrees
      (+0.83 mm) of flexion; mean laxities at 30 degrees, 45 degrees, 70 degrees, and
      90 degrees were unchanged. Forces in the remaining anterolateral bundle were not
      significantly different from those in the intact ligament for any mode of tibial
      loading, with the exception of the valgus moment, where sectioning of the PM
      bundle significantly reduced the PCL force at 0 degrees and 5 degrees of flexion.
      CONCLUSIONS: The relatively small increases in mean laxity after cutting of the
      PM bundle show that it plays a minor role in restraining posterior tibial
      translation. The minor changes in ligament force profiles after cutting of the PM
      bundle indicate that the remaining anterolateral bundle fibers continued to be
      loaded in a near-normal fashion. CLINICAL RELEVANCE: This study helps to
      elucidate the function of the PM bundle in the native PCL. Because only small
      changes were seen in the biomechanical parameters tested, the rationale for
      reconstructing this bundle of the PCL could be questioned.

PMID- 17027409
TI  - Tunnel expansion after anterior cruciate ligament reconstruction with autogenous
      hamstrings: a comparison of the medial portal and transtibial techniques.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of 2 techniques of
      drilling the femoral tunnel in anterior cruciate ligament (ACL) reconstruction
      (medial portal v transtibial) on tunnel expansion. METHODS: Autogenous hamstring
      ACL reconstructions performed by the senior author between July 1998 and July
      2004, with a minimum 6-month radiographic follow-up, using the transtibial
      technique (41 patients) and the medial portal technique (34 patients), were
      evaluated. All procedures were performed via an endoscopic technique with
      identical postoperative rehabilitation and graft fixation. Lateral and 45 degrees
      posteroanterior (PA) radiographs were obtained for each patient at a minimum of 6
      months postoperatively. The sclerotic margins of the femoral and tibial tunnels
      were measured at the widest dimension of the tunnel by 2 physicians and were
      compared with the initially drilled tunnel size after correction for radiographic
      magnification. Statistical analysis was performed to compare the 2 groups by use
      of the independent-samples t test, with significance set at .05. RESULTS: The
      mean percentage increase in the femoral tunnel was 38.20% +/- 17.76% for the
      medial portal technique and 53.96% +/- 21.72% for the transtibial technique on
      the PA view and 23.80% +/- 16.50% for the medial portal technique and 50.07% +/-
      26.98% for the transtibial technique on the lateral view. This difference was
      statistically significant on both PA and lateral views. The mean percentage
      increase in the tibial tunnel was 31.81% +/- 14.39% for the medial portal
      technique and 36.31% +/- 17.81% for the transtibial technique on the PA view and
      27.70% +/- 15.25% for the medial portal technique and 30.11% +/- 18.98% for the
      transtibial technique on the lateral view; however, these increases failed to
      reach statistical significance on either view. CONCLUSIONS: Femoral tunnel
      expansion for hamstring autologous ACL reconstructions is significantly lower for
      the medial portal technique when compared with the conventional transtibial
      technique. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic
      study.

PMID- 17027410
TI  - Mini-open arthroscopically assisted Bristow-Latarjet procedure for the treatment
      of patients with anterior shoulder instability: a cadaver study.
AB  - PURPOSE: The purpose of this study was to evaluate the arthroscopically assisted
      Bristow-Latarjet procedure. The aim was to use arthroscopic guidance to assist in
      positioning of the coracoid bone block onto the anterolateral aspect of the
      glenoid. The feasibility of this technique and its efficacy, reproducibility, and
      potential neurovascular complications were evaluated. METHODS: A minimally
      invasive technique was used to harvest the coracoid bone block and the attached
      coracobiceps tendon. A portal was created through the subscapularis muscle and,
      under arthroscopic guidance, the anterior aspect of the glenoid was cleaned and
      reamed before the bone block was placed. Cannulated screws (3.5 mm) were used to
      fix the vertically oriented bone block to the glenoid. The size of the bone
      block, its position on the glenoid, and its relation to the subscapularis tendon
      and the musculocutaneous and axillary nerves were recorded. RESULTS: In all 5
      cadavers, the bone block was well positioned and was fixed to the anteroinferior
      part of the glenoid. No lesions of the cephalic vein or of the surrounding
      neurovasculature were observed. CONCLUSIONS: This study demonstrated the safe and
      effective use of this arthroscopically assisted technique for correct positioning
      of the coracoid bone block at the anterolateral aspect of the glenoid in the
      cadaveric shoulder. Arthroscopy facilitated adequate reaming of the anterior
      glenoid and aided in optimal positioning of the bone block. CLINICAL RELEVANCE:
      This cadaveric study highlights the advantages offered by an arthroscopically
      assisted Bristow-Latarjet procedure, which optimizes positioning of the block and
      ensures adequate reaming of the anterior glenoid, thereby potentially reducing
      the risks of early nonunion and late arthritis--complications commonly associated
      with the classical Bristow-Latarjet technique.

PMID- 17027411
TI  - Reconstruction of lateral ligament with arthroscopic drilling for treatment of
      early-stage osteoarthritis in unstable ankles.
AB  - PURPOSE: The purpose of this study was to investigate the clinical, radiologic,
      and arthroscopic results of lateral stabilization with reconstruction of the
      lateral ligaments and cartilage regeneration with arthroscopic drilling for the
      treatment of moderate osteoarthritis of the ankle with simultaneous lateral
      instability of the ankle (LIA). METHODS: There were 16 cases with LIA, 7 of which
      had stage 2 osteoarthritis of the ankle according to the radiographic
      classification of Takakura et al. and 9 of which had stage 3 osteoarthritis.
      Arthroscopic drilling was performed with a motorized drill for the chondral
      defect, and anatomic reconstruction of the lateral ligament with an autologous
      gracilis tendon graft was performed for LIA. Clinical, radiologic, and
      arthroscopic evaluations were performed before surgery and at the most recent
      follow-up. RESULTS: In stage 2 cases the mean score on the American Orthopaedic
      Foot and Ankle Society ankle-hindfoot scale was 42.5 +/- 6.8 points before
      surgery and 87.4 +/- 4.2 points at the most recent follow-up (P = .0002). In
      stage 3 cases the mean score was 41.4 +/- 8.0 points before surgery and 61.2 +/-
      7.4 points at the most recent follow-up (P = .0001). The talar tilt angles on
      standard stress radiography in stage 2 cases were 17.4 degrees +/- 4.5 degrees
      before surgery and 3.4 degrees +/- 0.9 degrees at the most recent follow-up (P =
      .0009). In stage 3 cases the mean talar tilt angles were 18.2 degrees +/- 4.7
      degrees before surgery and 3.6 degrees +/- 0.7 degrees at the most recent follow
      up (P < .0001). In all cases the radiographic classification of Takakura et al.
      was unchanged between assessments before surgery and at the most recent follow
      up. With regard to arthroscopic findings at 1 year after surgery, the
      International Cartilage Repair Society's cartilage repair assessment score showed
      6 nearly normal and 1 abnormal stage 2 cases and 1 abnormal and 8 severely
      abnormal stage 3 cases. CONCLUSIONS: Reconstruction of the lateral ligament with
      arthroscopic drilling as a surgical procedure for the treatment of stage 2
      osteoarthritis with LIA can be recommended. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 17027412
TI  - Open and arthroscopic treatment of multidirectional instability of the shoulder.
AB  - Multidirectional instability of the shoulder can be a difficult diagnostic and
      therapeutic dilemma for orthopaedic surgeons. First described by Neer and Foster,
      the mainstay of treatment is usually conservative, with most patients doing very
      well with nonoperative management. In patients with recalcitrant symptoms,
      surgical treatment primarily has been aimed at addressing the pathologically
      increased capsular volume. Newer studies suggest that the pathology also includes
      abnormal labral morphology and perhaps inadequate neuromuscular control. The
      arthroscopic treatment of multidirectional instability has come to have
      comparable results to open techniques when the multifactorial nature of the
      disease is recognized and the multiple techniques are used in combination to
      fully treat all pathology. Thermal capsulorrhaphy cannot be recommended at this
      time, except perhaps as an adjunct to other capsular plication or capsulorrhaphy
      techniques. The advantages of a less invasive procedure make arthroscopic
      capsular plication attractive, but it is associated with increased technical
      difficulty and a steep learning curve. Further studies are needed to distinguish
      a clear advantage of one over the other. Regardless of the technique used, the
      key to success is addressing the capsular laxity and redundancy to restore
      anatomic capsuloligamentous tension without overconstraining the shoulder.

PMID- 17027413
TI  - Meniscal repair for anterior horn tear of the lateral meniscus.
AB  - This technical note describes all-inside meniscal repair for anterior horn tears
      of the lateral meniscus. A modified anteromedial portal is created for use in
      visualizing the anterior horn of the lateral meniscus. A crescent-shaped suture
      hook loaded with a polydioxanone suture (PDS) is inserted through an
      anterolateral portal. The hook tip penetrates the meniscal peripheral rim and
      advances across the tear. The suture hook penetrates the mobile central fragment.
      A leading limb of the PDS is advanced into the knee joint. Then, the leading limb
      of the suture is retrieved back to the anterolateral portal. With 2 limbs of PDS,
      endoscopic knot tying is done. With this simple technique, vertically oriented
      all-inside meniscal repair of an anterior horn tear of the lateral meniscus with
      the use of absorbable suture materials is easily performed.

PMID- 17027414
TI  - The accessory posteromedial portal revisited: utility for arthroscopic rotator
      cuff repair.
AB  - Arthroscopic rotator cuff repair is a technically challenging procedure.
      Accessory arthroscopic portals have been described that allow for optimal suture
      anchor placement, suture management, and knot tying. We describe here the
      usefulness of an accessory posteromedial portal that facilitates direct suture
      retrieval through the posterior aspect of a rotator cuff tear. This portal is
      created approximately 4 to 5 cm medial to the posterolateral corner of the
      acromion and 2 cm inferior to the scapular spine. The accessory posteromedial
      portal is especially useful when a retracted tear of the infraspinatus or teres
      minor is encountered. Because these tendons retract in a posterior and medial
      direction, the accessory posteromedial portal places the tendon-penetrating
      device in an ideal position for suture passage through the posterior portion of
      the rotator cuff tear. This portal also allows placement of margin convergence
      sutures for large U-shaped or L-shaped tears by permitting a direct "hand-off" of
      the suture to or from a second penetrating device that is placed through a
      standard anterior portal. If multiple suture anchors are required (as in the case
      of large or massive cuff tears, or when double-row fixation is employed), sutures
      can be pulled out through the accessory posteromedial portal to facilitate suture
      management.

PMID- 17027415
TI  - The "cruciate suture" for arthroscopic meniscal repair: a new technique.
AB  - Meniscal repair has become the treatment of choice whenever a reparable tear is
      diagnosed. Fixation strength of the repair technique is always of paramount
      importance in comparison of various techniques, especially after the evolution of
      many arthroscopic all-inside devices. We present a new arthroscopic meniscal
      repair suturing technique called "cruciate suture." One 18-gauge needle and
      suture material are used. The needle is loaded with the suture material from its
      tip. The suture is folded at the tip of the needle, which is inserted to
      penetrate the skin obliquely to appear inside the joint, making a loop. The
      needle is retracted, while the suture is kept inside of it. The needle is
      reinserted at the same hole, appearing inside the joint and making a second loop.
      The needle is retracted completely. With the use of a probe, the loop at the
      second point is pulled through the loop at the first point, thereby forming a
      free end. The 2 limbs of the loop are pulled, thus driving the limb with the free
      end outside of the joint. The first oblique vertical suture is completed at this
      point. The needle is reloaded by the suture limb from the first point. The
      previous procedure is repeated, with use of the second skin hole and the third
      and fourth points to make the second oblique vertical suture. The cruciate suture
      is now complete. We tested the ultimate tension load (UTL) of the cruciate suture
      in comparison with that of the vertical suture (the gold standard). A total of 36
      tests (18 for the cruciate suture and 18 for the vertical suture) were performed
      on human menisci. The mean UTL of the cruciate suture was measured at 110 N; the
      mean UTL of the vertical suture was 67 N.

PMID- 17027416
TI  - Arthroscopic technique for patch augmentation of rotator cuff repairs.
AB  - The patient is placed in the lateral position, and an arthroscopic cuff repair is
      performed according to standard techniques. The line of repair is usually in the
      shape of a "T" or an "L." The repair is viewed through the lateral portal, with
      fluid inflow through the scope. Mattress sutures are placed in the anterior and
      posterior portions of the cuff, with respect to the line of repair, just medial
      to the most medial point of the tear. The sutures are placed in accordance with
      margin convergence suture passing methods. Next, 2 double-stranded suture anchors
      are placed into the lateral aspect of the greater tuberosity, which can be used
      to secure the anterior and posterior portions of the rotator cuff as well as the
      patch. The cuff sutures are tied first; then, the patch is addressed. The graft
      is sized by placement of a ruled probe or similar device into the subacromial
      space. The length of each side of the "rectangle" is measured to obtain the
      dimensions of the patch. The patch is then cut to fit the measurements. If the
      patch material is elastic, a slightly smaller than measured graft is cut to
      provide tension on the repair. The arthroscope is then moved to the posterior
      portal, and a large (8 mm) cannula, with a dam, is placed into the lateral
      portal. All sutures are brought out of the lateral cannula, and corresponding
      ends of each suture are held together in a clamp. The sutures are placed in their
      respective orientations once outside the cannula (e.g., anterior-medial, anterior
      lateral), covering all 4 quadrants. Care is taken to ensure that the sutures have
      no twists and are not wrapped around one another. The sutures are passed through
      the graft, in mattress fashion, with a free needle, in their respective corners
      and clamped again. The graft is then grasped with a small locking grasper on its
      medial edge and is passed through the cannula into the subacromial space. The
      clamps holding the sutures are then gently pulled to remove the slack. A smaller
      (5 mm) cannula is placed through 1 of the anchor incisions into the subacromial
      space. The medial 2 sutures are retrieved, a pair at a time, through the small
      cannula and are tied according to standard arthroscopic techniques; then, the
      lateral 2 sutures are retrieved from the anchor. The graft should cover the area
      of repair completely and should be under slight tension. Additional sutures may
      be placed to further secure or tension the graft as necessary, with the use of
      standard suture passing techniques, similar to those used when margin convergence
      is performed. Passive shoulder motion, pendulum exercises, and active elbow and
      wrist motion begin 2 days after surgery when the dressing is removed. Active
      assisted motion and active motion begin at 6 weeks, with integrated periscapular
      stabilization exercises. Formal cuff strengthening begins no sooner than 12 weeks
      after surgery for large and massive tears.

PMID- 17027417
TI  - Trans-cuff portal for arthroscopic posterior capsulorrhaphy.
AB  - Arthroscopic repair of posterior shoulder instability is becoming an accepted
      method of treatment. Most surgeons perform this procedure with the patient in a
      lateral decubitus position to facilitate access to the posterior glenoid. We have
      developed an accessory portal placed through the midportion of the rotator cuff
      that allows easy and complete viewing of the posterior glenohumeral joint when
      the patient is in a beach chair position and does not require the use of
      traction. This portal provides a superior-to-inferior view of the posterior
      glenoid rim and capsule and allows use of anterior and posterior routine portals
      for posterior Bankart repair. In this study, the technique of posterior labral
      repair in the beach chair position with use of the trans-cuff portal is
      described, and preliminary results in 5 patients at an average follow-up of 24
      months are presented. Through this approach, we were able to place 3 anchors,
      with the lowest at the 7 o'clock position (for a right shoulder), in all
      patients. Mean American Shoulder Elbow Surgeons (ASES) score improved from 53 +/-
      15 preoperatively to 87 +/- 8 postoperatively (P < .01). All patients had an
      excellent result with complete resolution of pain and instability.

PMID- 17027418
TI  - Calcific tendonitis of the subscapularis tendon causing subcoracoid stenosis and
      coracoid impingement.
AB  - Calcific tendonitis is a common disease of the shoulder which usually responds to
      conservative treatment. In cases unresponsive to conservative management,
      arthroscopic treatment is sometimes required. While there are several reports on
      calcifications within the supraspinatus tendon, documented cases involving the
      subscapularis tendon are rare. We present a case of a 47 year old farmer with
      recurrent anterior shoulder pain. An MRI revealed calcium deposits as well as a
      large subcoracoid cyst. Arthroscopic excision of the multiple calcific deposits
      left a large defect in the subscapularis tendon which was repaired back to the
      lesser tuberosity using arthroscopic techniques. A coracoplasty resulted in an
      increased coracohumeral space. The patient followed a conservative postop
      rehabilitation protocol and ultimately regained full strength and was pain free
      at the latest follow-up. We postulate two possible etiologies of subscapularis
      calcific tendonitis: either an idiopathic calcific tendonitis caused a secondary
      coracoid impingement or a primary subcoracoid stenosis resulted in an
      interstitial subscapularis tear which eventually resulted in calcium deposition.
      This report describes the clinical and technical details of arthroscopic excision
      of calcific deposits of the subscapularis tendon as well as arthroscopic repair
      of the resulting subscapularis defect.

PMID- 17027419
TI  - Arthroscopic debridement and irrigation of periprosthetic total elbow infection.
AB  - We report on a case of arthroscopic treatment of septic arthritis of the elbow
      joint in a 65-year-old man with an elbow endoprosthesis. Two months after
      arthroplasty of the elbow joint, the patient developed acute septic arthritis of
      the right elbow. Methicillin-sensitive Staphylococcus aureus was identified as
      the causative organism. Six days after the onset of symptoms, the patient was
      treated with a single arthroscopic procedure of the infected periprosthetic
      joint, including irrigation with 5 L of Ringer's lactate solution, debridement,
      and partial synovectomy with a 4.5-mm curved shaver. Intravenous antibiotic
      therapy was also used for 3 months including rifampicine and fucidic acid
      according to the intraoperative cultures. The acutely infected total elbow
      arthroplasty could be cured without removal of the endoprosthesis of the elbow.
      Ten months postoperatively, the patient remains free of symptoms and his blood
      rates are within normal limits.

PMID- 17027420
TI  - Incidences of frostbite in arthroscopic knee surgery postoperative cryotherapy
      rehabilitation.
AB  - A retrospective study of 4 cases of frostbite was undertaken to examine causes
      and to identify related contributory behaviors and circumstances. These patients
      underwent various surgical interventions before the onset of frostbite during
      similar postoperative care regimens. Surgical procedures included some of the
      following in each patient: lateral retinacular release, vastus medialis oblique
      muscle advancement, partial medial meniscectomy, chondromalacia patella,
      trochlea, medial and lateral femoral condyle debridement, lateral retinaculum
      release, and excision of medial plica. The mechanism of onset, development, and
      sites of frostbite were uniform in all patients. In every case, the sites were
      located in the area on top of the patella including some adjacent regions
      depending on the size of each injury. Frostbite locations were correlated with
      the part of the cryotherapy cold cuff device located on top of the patellar
      region. This cuff portion was originally designed to accommodate surgical trauma
      induced during autogenous bone-tendon-bone graft harvest in anterior cruciate
      ligament reconstruction surgery. Locating cryotherapy over this region assisted
      in minimizing pain and effusion for patients subsequent to distal patella bone
      plug harvest trauma. However, the requirement for use of the pad in the patella
      area for patients not undergoing anterior cruciate ligament reconstruction with
      autograft was found to be unnecessary and was the primary cause of frostbite in
      the cases presented here.

PMID- 17027421
TI  - Why are so few randomized trials useful, and what can we do about it?

PMID- 17027422
TI  - The Trial Protocol Tool: The PRACTIHC software tool that supported the writing of
      protocols for pragmatic randomized controlled trials.
AB  - OBJECTIVE: To develop a tool that would make it easier for researchers,
      especially those in low- and middle-income countries, to write research protocols
      for pragmatic randomized controlled trials. STUDY DESIGN AND SETTING: A series of
      focus groups was held at the inaugural meeting of the Pragmatic RAndomized
      Controlled Trials in Health Care (PRACTIHC) project in 2001 to develop a desired
      specification for the Trial Protocol Tool. A working group of five individuals
      from the PRACTIHC group was formed to develop content for the tool. RESULTS: The
      Trial Protocol Tool was developed in English and Spanish as a Microsoft Windows
      HTML help system. A Web-based version is also available. This main body of the
      tool provides information, advice, and resources about the major headings that
      should be part of every research protocol. Illustrative examples are used
      throughout and are taken directly from the tool's protocol library. Additional
      resources include checklists, programs (e.g., a sample size calculator), and
      example documents (e.g., patient information leaflets). CONCLUSION: The Trial
      Protocol Tool packages all the key requirements for the development of a research
      protocol into one resource. We believe that the use of the tool will help
      researchers to design effective trials and to write high-quality protocols.

PMID- 17027423
TI  - Recommendations for reporting randomized controlled trials of herbal
      interventions: Explanation and elaboration.
AB  - Controlled trials that use randomized allocation are the best tool to control for
      bias and confounding in trials testing clinical interventions. Investigators must
      be sure to include information that is required by the reader to judge the
      validity and implications of the findings in the reports of these trials. In
      part, complete reporting of trials will allow clinicians to modify their clinical
      practice to reflect current evidence toward the improvement of clinical outcomes.
      The consolidated standards of reporting trials (CONSORT) statement was developed
      to assist investigators, authors, reviewers, and editors on the necessary
      information to be included in reports of controlled clinical trials. The CONSORT
      statement is applicable to any intervention, including herbal medicinal products.
      Controlled trials of herbal interventions do not adequately report the
      information suggested in CONSORT. Recently, reporting recommendations were
      developed in which several CONSORT items were elaborated to become relevant and
      complete for randomized controlled trials of herbal medicines. We expect that
      these recommendations will lead to more complete and accurate reporting of herbal
      trials. We wrote this explanatory document to outline the rationale for each
      recommendation and to assist authors in using them by providing the CONSORT items
      and the associated elaboration, together with examples of good reporting and
      empirical evidence, where available, for each. These recommendations for the
      reporting of herbal medicinal products presented here are open to revision as
      more evidence accumulates and critical comments are collected.

PMID- 17027424
TI  - Claude Bernard was a 19th century proponent of medicine based on evidence.
AB  - The French physiologist Claude Bernard (1813-1878) has the unfair reputation of
      being ferociously opposed to the use of probabilities and statistics in medicine.
      In the 19th century, he would have been included among those who opposed the
      emergence of what would eventually become clinical epidemiology. The truth is
      that Bernard valued the role of medical statistics in clinical medicine but
      viewed it as potentially misleading in laboratory-based physiology. He posited
      that clinical medicine had to be guided by probabilistic evidence as long as
      physiological mechanisms remained unknown. Bernard praised the clinical
      researches of Pierre Louis aiming to assess the efficacy of bloodletting in the
      treatment of pneumonitis. The real objects of Bernard's contempt were the
      physicians who pretended that medicine was an art strictly based on intuition and
      tact and who pretended that comparative trials and statistics were useless for
      clinical medicine. Overall, Bernard was a strong and explicit proponent of the
      importance of scientific evidence in medical knowledge, be it from experiments or
      from comparative trials.

PMID- 17027425
TI  - Recurrent events counted in evaluations of predictive accuracy.
AB  - OBJECTIVES: To describe an alternate approach for the calculation of sensitivity
      and specificity when analyzing the accuracy of screening tools, which can be used
      when standard calculations may be inappropriate. Sensitivity(ER) (ER denoting
      event rate) is the number of events correctly predicted, divided by the total
      number of events. Specificity(ER) is the amount of time that study participants
      are predicted to be event negative, divided by the total amount of participant
      observed time. Variance estimates for these statistics are constructed by
      bootstrap resampling, taking into account event dependence. METHODS: Standard and
      alternate approaches for calculating sensitivity and specificity were applied to
      hospital falls risk screening tool data. In this application, the outcome of
      interest was a recurrent event, there were multiple applications of the screening
      tool, delays in screening tool completion, and patients' follow-up durations were
      unequal. RESULTS: Application of sensitivity(ER) and specificity(ER) to this data
      not only provided a clearer description of the screening tool's overall accuracy,
      but also allowed examination of accuracy over time, accuracy in predicting
      specific event numbers, and evaluation of the added value that screening tool
      reapplications may have. CONCLUSION: Sensitivity(ER) and specificity(ER) provide
      a valuable approach to screening tool evaluation in the clinical setting.

PMID- 17027426
TI  - Empirical-Bayes adjustment improved conventional estimates in postmarketing drug
      safety studies.
AB  - OBJECTIVES: Empirical-Bayes adjustment was used to investigate the effects of
      antibacterials on risk of arrhythmia in a large cohort study based upon automated
      record linkage. STUDY DESIGN AND SETTING: The Prescription Drug Database of the
      Varese Province, Italy, was used to form a population-based cohort of patients
      who received at least one prescription of antibacterials for systemic use. All
      cohort members were followed-up from the beginning of each antibacterial
      therapeutic cycle up to 60 days afterward, identifying the first prescription of
      an antiarrhythmic drug and/or the first admission for arrhythmia. Standardized
      incidence ratios for eight classes of antibacterials, as well as for the specific
      antibacterial drugs, were estimated using both conventional methods and empirical
      Bayes (EB) adjustment. RESULTS: Using EB adjustment, overall precision was
      greatly enhanced compared to the conventional analysis. Statistical evidence of
      drug-induced dysrhythmic events was found for 17 drugs mostly belonging to
      Macrolides and Quinolones. Strongest proarrhythmic effects were found for
      Ciprofloxacin (standardized incidence ratio [SIR]: 1.98; 95% CI: 1.67, 2.34) and
      Erythromycin (SIR: 1.91; 95% CI: 1.20, 2.88). CONCLUSION: Empirical-Bayes may
      mitigate some problems inherent the conventional analysis. Macrolides and
      Quinolones were associated with the highest number of positive signals of
      dysrhythmic events. This requires further investigation by other types of
      epidemiologic studies.

PMID- 17027427
TI  - A comparison of two consensus methods for classifying morbidities in a single
      professional group showed the same outcomes.
AB  - OBJECTIVE: To investigate whether consensus differs when reached by the Nominal
      or the Delphi method. STUDY DESIGN AND SETTING: Seventeen general practices from
      North Staffordshire, England were randomly allocated to Delphi (postal feedback
      only) or Nominal group (also had group discussion). General practitioners
      classified 56 morbidities according to four scales of severity (chronicity, time
      course, health care use, patient impact) in two consensus rounds. Consensus
      outcomes were assessed by between-group comparison of severity scores at baseline
      and follow-up rounds, and consensus process by within-group change in the
      variance of severity scores between the two rounds. RESULTS: Consensus rounds
      were completed by 21 out of 35 Nominal GPs and 23 out of 43 Delphi GPs. Baseline
      scores for three of the four severity scales were significantly higher for
      Nominal compared to Delphi GPs, but there were no differences at follow-up.
      Between the two rounds, variance reduced within the Nominal and Delphi group,
      respectively, by 61% and 35% (chronicity), 40% and 62% (time course), 42% and 36%
      (health care use), and 19% and 38% (patient impact). CONCLUSION: The Nominal and
      Delphi methods did not result in different outcomes and we conclude that either
      method can be used in health services research.

PMID- 17027428
TI  - Computer adaptive testing improved accuracy and precision of scores over random
      item selection in a physical functioning item bank.
AB  - BACKGROUND AND OBJECTIVE: Measuring physical functioning (PF) within and across
      postacute settings is critical for monitoring outcomes of rehabilitation;
      however, most current instruments lack sufficient breadth and feasibility for
      widespread use. Computer adaptive testing (CAT), in which item selection is
      tailored to the individual patient, holds promise for reducing response burden,
      yet maintaining measurement precision. We calibrated a PF item bank via item
      response theory (IRT), administered items with a post hoc CAT design, and
      determined whether CAT would improve accuracy and precision of score estimates
      over random item selection. METHODS: 1,041 adults were interviewed during
      postacute care rehabilitation episodes in either hospital or community settings.
      Responses for 124 PF items were calibrated using IRT methods to create a PF item
      bank. We examined the accuracy and precision of CAT-based scores compared to a
      random selection of items. RESULTS: CAT-based scores had higher correlations with
      the IRT-criterion scores, especially with short tests, and resulted in narrower
      confidence intervals than scores based on a random selection of items; gains, as
      expected, were especially large for low and high performing adults. CONCLUSION:
      The CAT design may have important precision and efficiency advantages for point
      of-care functional assessment in rehabilitation practice settings.

PMID- 17027429
TI  - Longer response scales improved the acceptability and performance of the
      Nottingham Health Profile.
AB  - OBJECTIVE: To test alternative response formats for the Nottingham Health Profile
      (NHP), in terms of acceptability, score distributions, and measurement
      properties. STUDY DESIGN AND SETTINGS: Randomized trial of four response formats
      for the NHP: original "yes/no" format, a 3-point similarity format ("applies
      completely/in part/not at all"), a 5-point intensity format ("completely true" to
      "completely false"), and a 5-point frequency format ("all the time" to "never").
      Respondents were patients discharged from a hospital. We compared scores
      distributions, reliability coefficients, correlations with dimension-specific
      numerical scales, and patient ratings of the instrument. RESULTS: Response rates
      were similar for the four versions. The original response format had the fewest
      fully completed questionnaires, and the largest ceiling effects. Internal
      consistency and test-retest coefficients were acceptable for all versions, but
      were higher for the two 5-point formats. Correlations reflecting convergent and
      discriminant validity were higher for the longer response formats than for the
      original version. The frequency format received the highest ratings from
      patients, particularly from the sicker and older subgroups. CONCLUSIONS: The
      psychometric performance and patient acceptability of the NHP can be improved by
      using a 5-point frequency response format instead of the original dichotomous
      response format.

PMID- 17027430
TI  - Heritabilities and shared environmental effects were estimated from household
      clustering in national health survey data.
AB  - OBJECTIVES: The relative contributions of genetic and environmental variables to
      within-household clustering of quantitative traits in household surveys are
      poorly characterized. We estimated shared genetic and shared environmental
      contributions to within-household correlation for anthropometric variables and
      cardiovascular disease risk factors. STUDY DESIGN AND SETTING: Data were analyzed
      for the Health Survey for England 1998, a representative national household
      survey. Two-generation pedigrees were defined using information for relationships
      within households. After standardizing for age and sex, data were analyzed for 11
      quantitative traits. Variance components models were fitted to estimate the
      proportion of variance due to additive genetic variance or shared environmental
      effects. RESULTS: Within-household correlation coefficients for all related and
      unrelated subjects ranged from 0.10 for C-reactive protein to 0.31 for height.
      Pairwise correlations between related individuals within households were
      consistently higher than those between unrelated individuals. Estimated
      heritability ranged from 6% for diastolic blood pressure to 40% for serum
      cholesterol. The proportion of variance attributable to shared environmental
      effects ranged from 8% for cholesterol to 24% for height. CONCLUSION: In this
      large, representative national sample of generally small families, estimates for
      heritability were generally lower than previously reported, whereas the
      contribution of shared environment and individual-level variation were greater.

PMID- 17027431
TI  - A new method of analysis enabled a better understanding of clinical practice
      guideline development processes.
AB  - OBJECTIVE: To describe the process by which various forms of evidence are
      discussed, valued, and interpreted within the process of developing evidence
      based clinical practice guidelines and, in so doing, to develop a method for such
      studies. STUDY DESIGN AND SETTING: An observational study. Two guideline
      development groups were observed by a nonparticipant observer. The 21 meetings
      were recorded, transcribed, and analyzed using grounded theory and frame
      analysis. Qualitative analysis was complemented with descriptive statistics.
      RESULTS: The groups organized their discussion around four domains--'science',
      'practice', politics', and 'process'--and used boundary work to mediate between
      these domains. Both groups spent most time discussing 'science', followed by
      'practice' or its relation with 'science'. CONCLUSION: Our analysis offers an
      innovative, replicable method of analysis of guideline development that permits
      the identification of the proportions and interrelations between knowledge
      domains deployed by guideline groups. This analysis also suggests that the
      participation hierarchy observed here and by others might be an effect of the
      imbalanced use of knowledge domains in the construction of clinical guidance.
      This constitutes an important framework to understand the interplay of
      participants and knowledge in guideline development.

PMID- 17027432
TI  - Prediction of asthma in young adults using childhood characteristics: Development
      of a prediction rule.
AB  - OBJECTIVE: To develop an easily applicable prediction rule for asthma in young
      adulthood using childhood characteristics. METHODS: A total of 1,055 out of 1,328
      members of a Dutch birth cohort were followed from 2 to 21 years of age.
      Univariate and multivariate logistic regression analyses were used to evaluate
      the predictive value of childhood characteristics on asthma at 21 years of age. A
      prognostic function was developed, and the area under the receiving operating
      characteristic (ROC) curve was used to estimate the predictive ability of the
      prognostic models. RESULTS: Of the 693 responding subjects, 86 (12%) were
      diagnosed with asthma. Independent prognostic factors at ages 2 and 4 years were
      female gender (odds ratios (OR) 1.9 and 2.1; 95% confidence intervals (CI) 1.2
      3.2 and 1.3-2.5), smoking mother (OR 1.6 and 1.6; CI 1.0-2.7 and 1.0-2.6), lower
      respiratory tract illness (OR 1.9 and 2.4; CI 1.0-3.6 and 1.4-4.0), and atopic
      parents (OR 2.1 and 1.9; CI 1.3-3.4 and 1.2-3.1). The predictive power of both
      models was poor; area under ROC curve was 0.66 and 0.68, respectively.
      CONCLUSION: Asthma in young adulthood could not be predicted satisfactorily based
      on childhood characteristics. Nevertheless, we propose that this method is
      further tested as a tool to predict development of asthma.

PMID- 17027433
TI  - Health problems were the strongest predictors of attrition during follow-up of
      the GAZEL cohort.
AB  - BACKGROUND AND OBJECTIVES: This study examined socioeconomic, lifestyle, and
      health factors associated with response to annual mail questionnaires in a
      longitudinal study from 1990 through 2000 within the French GAZEL cohort.
      METHODS: Twenty thousand six hundred twenty-four participants volunteered in
      1989, and received each year a questionnaire. As responding one given year was
      not independent of responding in other years, mixed models were used to analyze
      the variables associated with response. RESULTS: Higher response rates were
      associated with gender (male), age (older), managerial status, and retirement.
      Smoking and alcohol drinking at baseline were associated with lower
      participation. Subjects who had at least three sick leaves were less likely to
      respond, especially for absence for psychiatric and alcohol-related diseases
      among men. Those who had rated their health as bad at baseline were less prone to
      respond during the follow-up. Attrition in subsequent response to questionnaires
      was associated with cancer diagnosis and with episodes of coronary heart disease
      for men. CONCLUSION: Most of the variables that predicted initial participation
      were also associated with continued participation during follow-up. Health
      problems strongly predicted attrition, whereas socioeconomic factors played a
      weaker role. Withdrawing is a reversible state and considering only one episode
      of nonparticipation could be misleading.

PMID- 17027434
TI  - A low tension between individual and societal time aspects in health improved
      outcomes.
AB  - OBJECTIVES: To review intertemporal choices, involving decisions with a trade-off
      between something now and something later. These choices are common in health
      both at an individual and societal level. METHODS: The present value of an
      outcome, for example, the amount of money or the health outcomes in various
      aspects, is equivalent to the value of a future outcome discounted with the delay
      of time. The concept of diminishing value over time is positive discounting.
      Economic forecasts generally use discount rates in which the value of a future
      dollar is less than the value of a present dollar, and where the discount rates
      are similar for the individual investor and society. The value of future health
      is commonly thought of as similar to the value of future money. Yet, the
      individual may rationally choose a discount rate that is exceedingly low or even
      negative. This paradox is particularly relevant when considering primary and
      secondary prevention, where initial and continuing costs may precede beneficent
      outcomes by decades, making discount rate selections the dominant factor in
      determining decisions. CONCLUSION: We suggest that the societal perspective
      should also recognize that discount rates for health outcomes are largely
      irrelevant and that even negative discount rates have crucial relevance.

PMID- 17027435
TI  - Response to Carter et al.: A survey identified publication bias in the secondary
      literature.

PMID- 17027437
TI  - Nutrition and soccer: a primer.

PMID- 17027436
TI  - Oily fish reduces plasma triacylglycerols: a primary prevention study in
      overweight men and women.
AB  - OBJECTIVE: Previous studies have demonstrated benefits of high-dose long-chain
      omega-3 polyunsaturated fatty acid (LC omega-3 PUFA) supplements on metabolic
      risk. Effects of increased dietary omega-3 PUFA, via oily fish and/or plant
      derived omega-3 PUFAs, are less clear and may be modulated by the omega-6:omega-3
      PUFA of the habitual diet. This study examined the effect on cardiovascular
      disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in
      linoleic acid:alpha-linolenic acid (LA:LNA) and/or increasing LC omega-3 PUFA. It
      tested whether decreases in LA:LNA modulate effects of LC omega-3 PUFA. METHODS:
      One hundred forty-two subjects, recruited to a 24-wk randomized study, were
      assigned to a control group or one of four interventions. Intervention groups
      received two portions of oily fish (4.5 g eicosapentaenoic acid + docosahexanoic
      acid) or white fish (0.7 g eicosapentaenoic acid + docosahexanoic acid) per week,
      and replaced habitual household fats with ones high in sunflower (high LA:LNA) or
      rapeseed (low LA:LNA) oil. RESULTS: Modest dietary manipulations of omega-6 and
      omega-3 PUFAs resulted in significant group x time interactions for serum
      triacylglycerols (TAGs; P = 0.05); at 24 wk the control and two oily fish groups
      showed lower TAG than did the white fish/sunflower group (P = 0.05). Reductions
      in TAG, associated with increased oily fish intakes, were maximized when combined
      with lower dietary LA:LNA. There were no significant changes in several other
      cardiovascular disease risk markers. CONCLUSIONS: Two portions of oily fish per
      week led to significant reductions in TAG relative to consumption of two portions
      of white fish per week. Changes in TAG were maximized when combined with lower
      LA:LNA.

PMID- 17027439
TI  - Impact of average patient acuity on staffing of the phase I PACU.
AB  - The authors consider methods for determining staffing requirements for a Phase I
      PACU. Given that the total number of nursing hours per day is limited by
      budgetary constraints, PACU staffing can be adjusted to minimize the percentage
      of days that the PACU is full and cannot accept additional patients from the OR.
      Except for very small PACUs, the number of staffing options is so large that
      computer optimization methods must be used. In addition, patient acuity must be
      incorporated into the staffing plan. Methods are described for adjusting staffing
      requirements when some patient acuities differ from 1 nurse:2 patients, when
      patients transition from one acuity to another, and when acuity is not known for
      all patients.

PMID- 17027440
TI  - Effectiveness of femoral nerve blockade for pain control after total knee
      arthroplasty.
AB  - Control of postoperative pain is a major concern for patients undergoing total
      knee arthroplasty (TKA). The purpose of this study was to investigate pain
      control and opioid use, as well as length of stay, ambulation time, antiemetic
      use, and degree of mobilization for patients undergoing total knee arthroplasty,
      comparing those receiving femoral nerve block (FNB) to those receiving no femoral
      nerve block. Using retrospective patient record data, 133 subjects from an acute
      care community hospital in western Canada were split into three groups: no FNB
      (control group, n = 49), single-shot FNB (n = 33), and continuous FNB (n = 51).
      There was a statistically significant improvement in pain control on day of
      surgery for the FNB group compared with the no-FNB group, and reduction in opioid
      usage on days 0, 1, and 2 in the continuous FNB group compared with the no-FNB
      and single-shot group. Also noted was a statistically significant reduction in
      antiemetic use in the FNB compared with the no-FNB group on the day after
      surgery. This study is in accordance with earlier studies that support continuous
      FNB as an effective method for achieving postoperative pain control and reducing
      opioid use for patients undergoing TKA.

PMID- 17027441
TI  - Surgical site verification: A through Z.
AB  - Performing the correct procedure on the correct patient has always been of prime
      importance to all health care providers. For the past six years, it has been a
      patient safety initiative priority of the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO). Before JCAHO took the lead in this arena,
      however, health care facilities handled this issue with individualized policies
      and procedures. This became problematic because physicians practice in multiple
      institutions that could have conflicting policies, which could confuse the issue.
      This case study presents the evolution of the surgical side marking and site
      verification policy at St Joseph's Wayne Hospital, Wayne, NJ. It has been a
      painful process, requiring numerous policy rewrites with updated information as
      prescribed by JCAHO. Enforcing physician compliance and continually re-educating
      nurses with each new JCAHO change proved challenging. The marking of surgical
      sides and verification of all sites, however, has proven to be a collaborative
      effort with safe patient outcomes as the shared goal.

PMID- 17027442
TI  - Detection and treatment of perioperative corneal abrasions.
AB  - Corneal abrasion is the most common ocular injury occurring in the perioperative
      period. Corneal abrasion may occur during general anesthesia, monitored
      anesthesia care, regional anesthesia, or in the immediate recovery period. This
      injury is not usually apparent until the patient is in the PACU, and the
      perianesthesia nurse may be the first clinician to detect this complication.
      Preventive measures and vigilant care can help reduce the incidence of corneal
      abrasion in susceptible patients. Early detection and prompt intervention may
      help reduce the incidence of ocular morbidity. The purpose of this article is to
      explore the incidence, mechanism of injury, prevention, recognition, and
      treatment of perioperative corneal abrasion.

PMID- 17027443
TI  - Outcomes measurement in ambulatory surgery.

PMID- 17027444
TI  - Perianesthesia staffing...thinking beyond numbers.

PMID- 17027445
TI  - What a pain!

PMID- 17027446
TI  - A tragedy unfolds: lessons to learn.

PMID- 17027447
TI  - Binding mode of porphyrins to poly[d(A-T)(2)] and poly[d(G-C)(2)].
AB  - We examined the binding geometry of Co-meso-tetrakis (N-methyl pyridinium-4
      yl)porphyrin, Co-meso-tetrakis (N-n-butyl pyridinium-4-yl)porphyrin and their
      metal-free ligands to poly[d(A-T)(2)] and poly[d(G-C)(2)] by optical
      spectroscopic methods including absorption, circular and linear dichroism
      spectroscopy, and fluorescence energy transfer technique. Signs of an induced CD
      spectrum in the Soret band depend only on the nature of the DNA sequence; all
      porphyrins exhibit negative CD when bound to poly[d(G-C)(2)] and positive when
      bound to poly[d(A-T)(2)]. Close analysis of the linear dichroism result reveals
      that all porphyrins exhibit outside binding when complexed with poly[d(A-T)(2)],
      regardless of the existence of a central metal and side chain. However, in the
      case of poly[d(G-C)(2)], we observed intercalative binding mode for two
      nonmetalloporphyrins and an outside binding mode for metalloporphyrins. The
      nature of the outside binding modes of the porphyrins, when complexed with
      poly[d(A-T)(2)] and poly[d(G-C)(2)], are quite different. We also demonstrate
      that an energy transfer from the excited nucleo-bases to porphyrins can occur for
      metalloporphyrins.

PMID- 17027448
TI  - Anomalous phase transition in
      dipalmitoylphosphatidylethanolamine/palmitoylphosphatidylcholine/water system.
AB  - An anomalous phase transition with a marked rise in specific heat, the isobaric
      thermal expansion coefficient, and the compressibility coefficient at 62.5
      degrees C for an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine (DPPE) and 1-palmitoyl-sn-glycero-3-phosphocholine (PLPC), in
      water (34 wt.%) has been shown by differential scanning calorimetry, scanning
      dilatometry and isothermal compressibility measurements. This transition occurs
      15 degrees C above a first-order transition observed in the same system. (31)P
      and (2)H nuclear magnetic resonance results are consistent with the occurrence of
      'defects' in the bilayer in the temperature range between the first and the
      anomalous phase transitions. It is proposed that conically, PLPC molecules prefer
      regions with high curvature in the defective bilayer, while DPPE molecules are
      mostly confined to the flat regions of the bilayers.

PMID- 17027449
TI  - Thermodynamics of the hydration of non-polar substances.
AB  - We re-examine the numerical value and physical significance of T(S) the
      temperature where the entropy of transfer Delta(L)(W)S from the pure hydrocarbon
      liquid into water is zero. It is shown that the numerical value of T(S) depends
      on the convention adopted for calculating Delta(L)(W)G from solubility data at 25
      degrees C and on the Delta(L)(W)C(P) fitting function. It is concluded that the
      interpretation of T(S) as the temperature where hydration ceases cannot be
      sustained. As previously reported [R.L. Baldwin. N. Muller, Proc. Natl. Acad.
      Sci. USA, 89 (1992) 7110], hydration must vanish at a temperature T' > T(S),
      where its experimental manifestation, i.e., Delta(L)(W)C(P), is zero. We discuss
      the concept of water relaxation around a non-polar solute molecule and its
      relation to the hydration process.

PMID- 17027450
TI  - An improved approximate solution of the Lamm equation for the simultaneous
      estimation of sedimentation and diffusion coefficients from sedimentation
      velocity experiments.
AB  - Sedimentation and diffusion coefficients are important parameters to describe
      size and shape of macromolecules in solution. The data can be obtained from
      sedimentation velocity experiments by a nonlinear fitting procedure using
      approximate solutions for the Lamm equation. Here, we present a modification of
      such a model function that was originally proposed by Fujita [H. Fujita,
      Mathematical Theory of Sedimentation Analysis, Wiley, New York, 1962]. The
      extended model function is well suitable to study low molecular mass compounds.
      The improvement of this solution given here is based on using an adjustable value
      for the explicit integration variable, z, the reduced radius. This modification
      leads to more accurate sedimentation and diffusion coefficients compared to using
      a constant value of 0.5 as used by Fujita. The advantage of our modification was
      demonstrated by the analysis of noise-free curves calculated using the finite
      element method, as well as experimental curves obtained for the peptides
      angiotensin I and II. The relatively low sedimentation and diffusion coefficients
      found for both substances indicate that the peptides exist as extended chains of
      about 3.65 nm (angiotensin I) or 3.04 nm length (angiotensin II) in solution. The
      lack of higher-order structure of the peptides that was derived also from CD
      spectra might facilitate receptor binding, and could be one reason for the fast
      proteolytic digestion of the free peptides.

PMID- 17027451
TI  - Photophysics of ethidium bromide complexed to ct-DNA: a maximum entropy study.
AB  - Time-integrated and time-resolved fluorescence spectroscopies have been used to
      probe the photophysical properties of ethidium bromide (Eb) complexed to calf
      thymus DNA (ct-DNA). Fluorescence decay profiles are obtained using the technique
      of time-correlated single photon counting (TCSPC), and subsequently analysed
      using conventional sum-of-exponential (SOE) routines and also the maximum entropy
      method (MEM). Through use of these methods and simulated decay data, it is
      demonstrated that the kinetics of Eb in the presence of ds-DNA are best described
      by a generic model consisting of three exponential terms. At all DNA:Eb ratios
      and NaCl concentrations studied, free Eb is detected. Furthermore, Eb is found to
      interact with ds-DNA through two mechanisms, each distinguishable by its
      fluorescence decay time. Eb is shown to interact with DNA through classic
      intercalation, and also through binding at secondary sites. The component decay
      times are shown to be a function of NaCl concentration but independent of DNA:Eb
      molar ratio.

PMID- 17027452
TI  - Dynamic properties of individual water molecules in a hydrophobic pore lined with
      acyl chains: a molecular dynamics study.
AB  - Recently, a certain class of synthetic molecules has been shown to form ion
      channels, the pore of which is lined with hydrophobic acyl chains [M. Sokabe, in:
      F. Oosawa, H. Hayashi, T. Yoshioka (Eds.), Transmembrane Signaling and Sensation,
      JSSP/VNU Science Press BV, Tokyo, 1984, p. 119; F. Hayashi, M. Sokabe, M. Takagi,
      K. Hayashi, U. Kishimoto, Biochim. Biophys. Acta, 510 (1978) 305; M.J. Pregel, L.
      Jullien, J. Canceill, L. Lacombe, J.M. Lehn, J. Chem. Soc. Perkin Trans., 2
      (1995) 417; Y. Tanaka, Y. Kobuke, M. Sokabe, Angew. Chem. Int. Ed. Engl., 34
      (1995) 693; M. Sokabe, Z. Qi, K. Donowaki, H. Ishida, K. Okubo, Biophys. J., 70
      (1996) A201; H. Ishida, K. Donowaki, Y. Inoue, Z. Qi, M. Sokabe, Chem. Lett.
      (1997) p. 953]. As an initial step towards understanding the physical mechanisms
      of ion permeation across such a hydrophobic pore, systematic molecular dynamics
      simulations were performed to investigate dynamic and energetic properties of
      water molecules inside the pore using a dimer of alanine-N'-acylated cyclic
      peptide as a channel model. Dynamic energy profiles for water molecules indicated
      that the energy barrier at the middle region of the pore is approximately 2-3
      kcal/mol higher than that in the cap water region which was defined as a vicinity
      region of the channel entrance. Energetics analyses demonstrated that the mutual
      interactions among intrapore water molecules are the major factor to give
      favorable interaction (negative energy contribution) for themselves. The pore,
      despite being lined with acyl chains, has a favorable van der Waals interaction
      with intrapore water molecules. These results may help to explain why water
      filled channels can be formed by the hydrophobic helices in natural channels.

PMID- 17027453
TI  - Enzymatic reactions in small spatial volumes: comment on a model of Hess and
      Mikhailov.
AB  - Recently Hess and Mikhailov pointed out that in small subcellular compartments
      diffusion is so fast that mixing is instantaneous on the time scale of many
      enzymatic reactions. This opens the possibility for synchronizing individual
      reaction events. To illustrate this fact they discuss as example an irreversible
      enzymatic reaction with allosteric product activation. Under appropriate
      conditions their model shows coherent spiking in the number of product molecules,
      caused by the strong correlation between reaction events. In this model only
      substrate binding is an indeterministic process, all other subsequent transitions
      between different enzyme states being deterministic, contrary to real processes.
      The purpose of the present paper was to investigate this interesting phenomenon
      by means of a more realistic modification of the original model, with only
      probabilistic transitions. In an attempt to obtain spiking, which was not
      observed under these conditions, the model was extended to make a clear
      distinction between allosteric high and low affinity substrate binding, in
      contrast to the original model using a product dependent mean binding
      probability. However no periodic signal was detectable in the indeterministic
      version of the Hess Mikhailov model or the extended version, either by means of
      direct visualization or on autocorrelation or Fourier analysis. Reasons why
      spiking is not observed in indeterministic enzyme models are discussed.

PMID- 17027455
TI  - Sterically stabilized liposomes of DPPC/DPPE-PEG:2000. A spin label ESR and
      spectrophotometric study.
AB  - The chain dynamics and the thermotropic phase behavior of sterically stabilized
      liposomes obtained introducing in the host bilayer matrix of DPPC up to 7 mol% of
      the polymer-lipid DPPE-PEG:2000 were investigated by spin label electron spin
      resonance spectroscopy and spectrophotometry. The experimental data indicate that
      the dispersions have the dynamic and thermotropic characteristics of normal
      lamellar phase. Moreover, using spin labels that locate both in the interfacial
      and in the hydrocarbon regions, namely TEMPO-stearate, 5- and 16-PCSL, we find
      that relative to the unmodified DPPC bilayers, the polymer-grafted bilayers are
      loosely packed in the interfacial region and have reduced chain mobility in the
      gel phase. From the temperature dependence of the partition coefficient (P(c)),
      of the spin probe DTBN between the aqueous and the fluid hydrophobic regions of
      the bilayers and from the melting curves of the absorbance at 400 nm, we observe
      a slight influence on the endothermic phase transitions when increasing the
      concentration of the polymer-lipid in the DPPC bilayers, the influence being more
      evident in the pre-transition.

PMID- 17027456
TI  - Plant sterols: a neutron diffraction study of sitosterol and stigmasterol in
      soybean phosphatidylcholine membranes.
AB  - Neutron scattering experiments have been performed on oriented Soybean
      phosphatidylcholine (SPC) bilayers, containing sitosterol or stigmasterol, two
      major sterols of plant plasma membranes. Sitosterol and stigmasterol were either
      protonated or deuterated on position C25 of the lateral chain. Incorporation of
      sitosterol leads to an increase of the hydrophobic thickness of SPC bilayers of
      1.2 and 2 A when present, at 16 and 30 mol%, respectively. On the other hand, no
      change was observed when stigmasterol is present in the bilayer at its maximal
      solubility of 16 mol%. These results are in agreement with the fact that
      sitosterol is more efficient than stigmasterol to order acyl chains of SPC, as
      already shown with other biophysical techniques. In order to get more insight
      into the behavior of the lateral chains of the two sterols, the proton-deuterium
      contrast method was used in order to locate the (2)H25 atoms of the two sterols.
      For sitosterol, this atom was found close to the center of the bilayer at +/
      (1.6+/-0.2 A), with a width, nu=2.5+/-0.5 A. For stigmasterol, the difference
      profile could be fitted in two different ways: either two possible locations are
      found at +/-(2.3+/-0.2 A) and +/-(10+/-0.2 A) with the same width, nu=2.5+/-0.5 A
      or only one broad distribution at +/-(6.1+/-0.3 A), nu=8.5+/-0.7 A. The results
      are discussed in terms of difference of dynamics for the lateral chain of the two
      sterols.

PMID- 17027457
TI  - Hydration of diglycyl tripeptides with non-polar side chains: a volumetric study.
AB  - We have determined the apparent molar volumes and the apparent molar adiabatic
      compressibilities at 25 degrees C of 10 X-Gly-Gly and Gly-Gly-X tripeptides in
      which X represents a residue with a non-polar side chain. We also have determined
      the changes in volume and compressibility which accompany neutralization of the
      amino and carboxyl termini in these tripeptides. The mutual influence of the non
      polar side chain of the X residue and the terminal amino and carboxyl groups on
      the hydration of each other depends on the chemical nature of the side chain and
      the state of ionization of the termini. We interpret our data in terms of the
      hydration of the component aliphatic, aromatic, and charged atomic groups, as
      well as the mutual interactions between these groups.

PMID- 17027458
TI  - Mean-field analysis of protein-protein interactions.
AB  - Calculations were performed on the D1.3-E5.2 antibody-antibody complex estimating
      the binding affinities of the wild-type and 16 alanine substitutions. Analyzed
      were structural models of the interfacial region containing a zinc ion and
      crystallographic waters. A continuum approach was used to evaluate the
      electrostatic free energies and the hydrophobic effect was calculated by
      employing a buried molecular surface area relationship. Estimates of the absolute
      binding affinity reproduced the experimental value within the uncertainty of
      assessing entropic and strain energy contributions. The best correlation for
      mutants with experimental data was achieved when the hydrophilicity of created
      cavities were considered, and yielded a correlation coefficient of 0.7 and an
      average error of +/-1.4 kcal/mol. Empirically fitting the free energy function
      produced a smaller error of +/-1.0 kcal/mol. Depending on the electrical
      potential and electrostatic reorganization, scaling the 'protein dielectric
      constant' to approximately 10 may improve the accuracy of continuum models for
      evaluating amino acid substitutions.

PMID- 17027460
TI  - Kinetic asymmetry as a key source of functional diversity in biochemical
      networks.
AB  - From the analysis of the dynamic properties of various symmetric and asymmetric
      kinetic schemes, the present report demonstrates that all kinetic schemes, which
      can be hypothetically divided into two equal halves about an axis of mirror
      symmetry, are endowed with structural metastability under mass-closed conditions.
      In mass-closed symmetric schemes, absolute symmetry in reaction conditions in two
      halves is essential for the occurrence of ordered dynamic behaviour. Even an
      infinitesimal deviation from the symmetry relations instantaneously drives such
      systems from limit-cycles to turbulence. Reaction schemes with no axes of
      symmetry may exhibit a large variety of complex, structurally stable temporal
      order for wide ranges of values of system parameters and variables. Kinetic
      asymmetry, therefore, may confer to biochemical networks the functional diversity
      as well as stability against environmental perturbations.

PMID- 17027461
TI  - Effect of cation and anion of an electrolyte on apparent molar volume, isentropic
      compressibility and refractive index of glycine in aqueous solutions.
AB  - Experiments at 298.15 K have been performed to measure the density, velocity of
      sound and refractive index in three water+glycine+electrolyte systems. The
      electrolytes studied were KCl, KNO3 and NaNO3. The values of apparent molar
      volume and isentropic compressibility of glycine in aqueous electrolyte solutions
      were calculated from the measured data. The results obtained in this study and
      those reported previously for water+glycine+NaCl system have been comparatively
      studied. The results show that the nature of both the cation and the anion of an
      electrolyte influence the behaviour of glycine in aqueous solutions. For all four
      electrolytes studied, the comparison shows a positive volume transfer for glycine
      from an electrolyte solution to a more concentrated solution of the same
      electrolyte. The results also show a negative apparent isentropic compressibility
      for glycine in the presence of the electrolytes studied. These effects indicate
      that the volume of a glycine molecule is larger in solutions with higher
      electrolyte concentration and the water molecules around the glycine molecules
      are less compressible than the water molecules in the bulk solution. These
      effects were attributed to the doubly charged behaviour of glycine and to the
      formation of physically bonded ion-pairs between the charged groups of glycine
      and the cation and the anion of the electrolyte.

PMID- 17027462
TI  - High pressure fourier transform infrared spectroscopy of poly(dA)poly(dT),
      poly(dA) and poly(dT).
AB  - The effect of hydrostatic pressure upon the DNA duplex, poly(dA)poly(dT), and its
      component single strands, poly(dA) and poly(dT) has been studied by fourier
      transform infrared spectroscopy (FT-IR). The spectral data indicate that at 28
      degrees C and pressures up to 12 kbar (1200 MPa) all three polymers retain the B
      conformation. Pressure causes the band at 967 cm(-1), arising from water
      deoxyribose interactions, to shift to higher frequencies, a result consistent
      with increased hydration at elevated pressures. A larger pressure-induced
      frequency shift in this band is observed in the single stranded polymers than in
      the double stranded molecule, suggesting that the effect of pressure on the
      hydration of single strands may be greater than upon a double stranded complex. A
      pressure-dependent hypochromicity in the bands attributed to base stacking
      indicates that pressure facilitates the base stacking in the three polymers, in
      agreement with previous assessments of the importance of stacking in the
      stabilization of DNA secondary structure at ambient and high pressures.

PMID- 17027463
TI  - Folding and unfolding of a giant duplex-DNA in a mixed solution with polycations,
      polyanions and crowding neutral polymers.
AB  - To understand the conformational behavior of a giant duplex-DNA chain in a mixed
      solution with various biopolymers with different state of ionization, the higher
      order structure of the DNA chain was analyzed with a fluorescence microscope in
      the presence of polycations (poly-arginine), polyanions (poly-glutamic acid), and
      neutral polymers (poly-ethylene glycol) as a model for cellular environment.
      Concentrated medium with neutral polymer induced the discrete folding transition
      of the DNA. At the threshold condition for the transition, addition of small
      amounts of either the polycation or the polyanion caused marked structural
      changes in the folded DNAs. Based on thermodynamic considerations on the
      experimental results, profile of free energy of a single giant DNA chain was
      depicted with respect to the size, or the expansion factor alpha, in the three
      dimensional structure of the DNA. The effect of the neural crowding polymer on
      the degree of folding of a single giant DNA chain is discussed in a semi
      quantitative manner.

PMID- 17027464
TI  - Effect of transport and competition on ligand binding.
AB  - We present a model to describe the physics of chemoreception in processes
      determined by competitive ligand binding. Our model describes the competition
      between various populations, such as ligands vs. blockers and receptors vs.
      decoys, in protein activation when diffusion is rate-determining. Full spatio
      temporal solutions can be obtained numerically. The model structure is kept
      simple enough as to permit its easy generalization to describe a large subset of
      the manifold of possible situations occurring in nature. The power and simplicity
      of the proposed method are exhibited through the solution of several examples
      which are discussed in detail.

PMID- 17027465
TI  - Conversions of the left-handed form and the protonated form of DNA back to the
      bound right-handed form by sanguinarine and ethidium: a comparative study.
AB  - The interaction of sanguinarine and ethidium with right-handed (B-form), left
      handed (Z-form) and left-handed protonated (designated as H(L)-form) structures
      of poly(dG-dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) was investigated by
      measuring the circular dichroism and UV absorption spectral analysis. Both
      sanguinarine and ethidium bind strongly to the B-form DNA and convert the Z-form
      and the H(L)-form back to the bound right-handed form. Circular dichroic data
      also show that the conformation at the binding site is right-handed, even though
      adjacent regions of the polymer have a left-handed conformation either in Z-form
      or in H(L)-form. Both the rate and extent of B-form to Z-form transition were
      decreased by sanguinarine and ethidium under ionic conditions that otherwise
      favour the left-handed conformation of the polynucleotides. The rate of decrease
      is faster in the case of ethidium as compared to that of sanguinarine. Scatchard
      analysis of the spectrophotometric data shows that sanguinarine binds strongly to
      both the polynucleotides in a non-cooperative manner under B-form conditions, in
      sharp contrast to the highly-cooperative binding under Z-form and H(L)-form
      conditions. Correlation of binding isotherms with circular dichroism data
      indicates that the cooperative binding of sanguinarine under the Z-form and the
      H(L)-form conditions is associated with a sequential conversion of the polymer
      from a left-handed to a bound right-handed conformation. Determination of bound
      alkaloid concentration by spectroscopic titration technique and the measurement
      of circular dichroic spectra have enabled us to calculate the number of base
      pairs of Z-form and H(L)-form that adopt a right-handed conformation for each
      bound alkaloid. Analysis reveals that 2-3 base pairs (bp) of Z-form of poly(dG
      dC).poly(dG-dC) and poly(dG-me5dC).poly(dG-me5dC) switch to the right-handed form
      for each bound sanguinarine, while approximately same number of base pairs switch
      to the bound right-handed form in complexes with H(L)-form of these
      polynucleotides. Comparative binding analysis shows that ethidium also converts
      approximately 2 bp of Z-form or H(L)-form to bound right-handed form under same
      experimental conditions. Since sanguinarine binds preferentially to alternating
      GC sequences, which are capable of undergoing the B to Z or B to H(L) transition,
      these effects may be an important part in understanding its extensive biological
      activities.

PMID- 17027466
TI  - Protein heat capacity: inconsistencies in the current view of cold denaturation.
AB  - The present study shows on the basis of the thermodynamic stability criterion
      (partial differential S/partial differential T)p>0 that partitioning of the
      entropy of cold-unfolding of a protein into independent positive conformational
      and negative hydrational contributions is incorrect. Furthermore it provides a
      new microscopic interpretation of protein heat capacity that takes into account
      the significant fluctuations in energy and entropy which result from the small
      size of these macromolecules.

PMID- 17027467
TI  - Effects of solvent perturbation on gelation driven by spinodal demixing.
AB  - We study effects of solvent perturbation on kinetic competition between spinodal
      demixing and gelation in agarose solutions at a concentration of 5 g/l. Two
      different cosolutes (tert-butyl alcohol and trimethyl amine N-oxide) known for
      altering in opposite way solvent-mediated interactions are chosen. By rheometry,
      static and dynamic light scattering experiments, we show that the cosolute
      presence shifts the boundary of the instability region of solution leaving
      unaffected temperature and polymer concentration values required for percolation.
      Results suggest that an appropriate choice of quenching temperature and solvent
      allows controlling the gelation time and the gel structural properties.

PMID- 17027468
TI  - Effects of diacylglycerol on the structure and phase behaviour of non-bilayer
      forming phospholipid.
AB  - The phase behaviour of mixed aqueous dispersions of the monomethyl derivative of
      dioleoylphosphatidylethanolamine and dipalmitoylglycerol has been characterised
      by X-ray diffraction, differential scanning calorimetry and freeze-fracture
      electron microscopy for mixtures containing dipalmitoylglycerol in the
      concentration range 0-20 mol%. Dispersions prepared at temperatures where the
      phospholipid exhibits a liquid-crystalline lamellar phase show that
      dipalmitoylglycerol is completely phase separated into aggregates of stable
      crystal phase (beta'-phase). Heating mixed dispersions results in transformation
      of lamellar into hexagonal-II structure commencing at approximately 45 degrees C.
      This temperature coincides with a disappearance of beta'-phase of DPG which
      becomes incorporated into hexagonal-II phase. The pure phospholipid is
      transformed upon cooling from hexagonal-II into characteristic cubic phases; the
      formation of cubic phase is prevented by the presence of dipalmitoylglycerol and
      mixed dispersions initially form a lamellar liquid-crystalline phase in which the
      lipids are phase separated. The X-ray and thermal data suggest that relatively
      small domains of metastable crystal phase (alpha-phase) of DPG form initially on
      cooling and these subsequently coalesce and transform to beta'-phase.

PMID- 17027469
TI  - Thermodynamic and spectroscopic features of the behavior of amphotericin B in
      aqueous medium.
AB  - The interaction between amphotericin B molecules in aqueous medium solution was
      studied using absorption and circular dichroism approaches. The results showed
      that at concentrations below 1 microM of amphotericin B, an equilibrium between
      the monomer and aggregate occurred with a constant of approximately 0.6x10(6) M(
      1). The aggregate formation constant was dependent on the experimental conditions
      of the medium: its value increased at acidic pH values, while alkaline medium
      induced the equilibrium displacement to the monomer formation. Either neutral
      salts or chaotropic agents such as urea prevented the formation of the aggregate.
      The presence of net electrical charge on the amine and carboxyl groups plays a
      role in the thermodynamic stability of the aggregate. A hydrophobic effect was
      also found between the monomer form and the water molecules of neighbours. In the
      aggregate formation water molecules were released contributing to an increase in
      the entropic change.

PMID- 17027470
TI  - Lattice simulations of protein crystal formation.
AB  - A new algorithm is presented for the lattice simulation of protein crystal
      growth. The algorithm allows the calculation of the size distribution of
      microcrystals in the volume and timescale of experiments and within the framework
      of the previously-published microscopic model [A.M. Kierzek, W.M. Wolf, P.
      Zielenkiewicz, Biophys. J. 73 (1997) 571-580]. Simulations for the tetragonal
      lysozyme crystal show that there are two critical sizes in the development of
      ordered phase. The first one corresponds to the size of the smallest stable
      complex which, in the case of the tetragonal lysozyme crystal, is the particular
      tetramer. In a volume of 5 mul the tetramer appears in the millisecond timescale.
      The second critical radius of approximately 100 monomers is only reached by a few
      of all the smallest stable complexes formed in the solution. The model predicts
      that out of 10(7) tetramers which appear in solution, only eight reach the size
      of 100 monomers within 8 h. After exceeding the second critical radius the
      microcrystals grow to the size of 10(4) monomers in the minute timescale and are
      thus assumed to quickly lead to macroscopic crystals. The predicted number of
      crystals formed during 8 h of nucleation is in qualitative agreement with
      arrested nucleation experiments.

PMID- 17027471
TI  - Evolutionary contingency.

PMID- 17027472
TI  - Evolutionary convergence.

PMID- 17027473
TI  - Form and function in systems neuroscience.
AB  - 'Form follows function' is an architectural philosophy attributed to the great
      American architect Louis Sullivan, and later taken up by the Bauhaus movement. It
      stresses that the form of a building should reflect its function. Neuroscientists
      have used the converse of this dictum to learn the functions of neural circuits,
      believing that if we study neural architecture, it will lead us to an
      understanding of how neural systems function. New tools for studying the
      structure of neural circuits are being developed, so it is important to discuss
      what the old techniques have taught us about how to derive function from the form
      of a neural circuit.

PMID- 17027474
TI  - Evolvability.

PMID- 17027475
TI  - Neural basis of time changes during saccades.

PMID- 17027476
TI  - Archerfish shots are evolutionarily matched to prey adhesion.

PMID- 17027477
TI  - DNA topology: dynamic DNA looping.
AB  - The DNA in repressive loops is often tightly bent. DNA flexibility imposes
      significant constraints on their topology suggesting that they may exist as
      perturbations in plectonemic DNA.

PMID- 17027478
TI  - Growth control: p53, the guardian angel of compensatory proliferation.
AB  - Compensatory growth, or regeneration, is used to replace damaged tissue during
      animal development. Recent work has revealed a new role for Drosophila p53 in the
      compensatory proliferation of cells that are needed to repair damaged tissues, a
      role that requires the non-apoptotic function of the caspase protease Dronc.

PMID- 17027479
TI  - Nursing behavior: remembrance of things past.
AB  - Successful suckling is vital to the survival of mammalian newborns. In many
      mammals, nursing behavior is triggered by maternally derived odors. Such odors
      may also promote the learned association of odorant cues present in the
      environment during nursing.

PMID- 17027480
TI  - Replicative helicases: a staircase with a twist.
AB  - The first crystal structure of a ring helicase encircling single-stranded DNA
      reveals a mechanism for ATP-dependent DNA translocation.

PMID- 17027481
TI  - Perception: transient disruptions to neural space-time.
AB  - How vision operates efficiently in the face of continuous shifts of gaze remains
      poorly understood. Recent studies show that saccades cause dramatic, but
      transient, changes in the spatial and also temporal tuning of cells in many
      visual areas, which may underly the perceptual compression of space and time, and
      serve to counteract the effects of the saccades and maintain visual stability.

PMID- 17027482
TI  - Transcription: adjusting to adversity by regulating RNA polymerase.
AB  - Under growth-limiting conditions, budding yeast shut down transcription of genes
      of the translation apparatus. Recent studies have shown that this response is
      signaled, in part, by multiple pathways that converge on Maf1, leading to a
      change of this protein's phosphorylation state and its relocation to the nucleus,
      where it represses RNA polymerase III.

PMID- 17027483
TI  - Animal cognition: an insect's sense of time?
AB  - For Immanuel Kant, time was the very form of the inner sense, the bedrock of our
      consciousness and also the origin of arithmetic ability. New research on
      bumblebees has shown that even an invertebrate with a brain the size of a pinhead
      can actively sense the passage of elapsed time, allowing it to predict when
      certain salient events will occur in the future.

PMID- 17027484
TI  - G-protein signaling: a new branch in an old pathway.
AB  - A recent study provides evidence for a new branch of the yeast mating pathway in
      which a G-protein alpha subunit directly activates phosphatidylinositol 3-kinase
      at endosomes.

PMID- 17027485
TI  - A novel Eph receptor-interacting IgSF protein provides C. elegans motoneurons
      with midline guidepost function.
AB  - BACKGROUND: The ventral midline is a prominent structure in vertebrate and
      invertebrate nervous systems that provides crucial topological information for
      guiding axons to their appropriate target destinations. Rather than being
      composed of specialized midline glia cells as in many other species, the
      embryonic midline of the nematode Caenorhabditis elegans is physically defined by
      motoneuron cell bodies that separate the left from the right ventral cord
      fascicles. Their function during development, if any, is not known. RESULTS: We
      show here that besides being components of the postembryonic locomotory circuit,
      these embryonic motoneurons (eMNs) actively provide midline guidance information
      for a specific subset of ventral midline axons. This information is provided in
      the form of a novel, cell-surface-anchored immunoglobulin superfamily (IgSF)
      member, WRK-1. WRK-1 acts in eMNs to prevent follower axons from inappropriately
      crossing the ventral midline. We describe the function of the Eph receptor vab-1
      and multiple ephrin ligands at the midline, and we show by double mutant analysis
      and physical interaction tests that WRK-1 functionally interacts with the Eph
      receptor system. This interaction appears to occur exclusively in the context of
      axon guidance at the ventral midline but not in other cellular contexts, thereby
      suggesting that Eph receptor signaling is mechanistically distinct in different
      tissue types. CONCLUSIONS: Our studies reveal cellular and molecular components
      of axon midline patterning and suggest that Ephrin signaling relies on previously
      unknown accessory components.

PMID- 17027486
TI  - Seeing or doing? Influence of visual and motor familiarity in action observation.
AB  - The human brain contains specialized circuits for observing and understanding
      actions. Previous studies have not distinguished whether this "mirror system"
      uses specialized motor representations or general processes of visual inference
      and knowledge to understand observed actions. We report the first neuroimaging
      study to distinguish between these alternatives. Purely motoric influences on
      perception have been shown behaviorally, but their neural bases are unknown. We
      used fMRI to reveal the neural bases of motor influences on action observation.
      We controlled for visual and knowledge effects by studying expert dancers. Some
      ballet moves are performed by only one gender. However, male and female dancers
      train together and have equal visual familiarity with all moves. Male and female
      dancers viewed videos of gender-specific male and female ballet moves. We found
      greater premotor, parietal, and cerebellar activity when dancers viewed moves
      from their own motor repertoire, compared to opposite-gender moves that they
      frequently saw but did not perform. Our results show that mirror circuits have a
      purely motor response over and above visual representations of action. We
      understand actions not only by visual recognition, but also motorically. In
      addition, we confirm that the cerebellum is part of the action observation
      network.

PMID- 17027487
TI  - Distinct developmental mechanisms reflect the independent origins of leaves in
      vascular plants.
AB  - Vascular plants diverged more than 400 million years ago into two lineages, the
      lycophytes and the euphyllophytes . Leaf-like organs evolved independently in
      these two groups . Microphylls in lycophytes are hypothesized to have originated
      as lateral outgrowths of tissue that later became vascularized (the enation
      theory) or through the sterilization of sporangia (the sterilization hypothesis)
      . Megaphylls in euphyllophytes are thought to represent modified lateral branches
      . The fossil record also indicates that the seed plant megaphyll evolved uniquely
      in the ancestor of seed plants, independent of megaphylls in ferns, because seed
      plants evolved from leafless progymnosperm ancestors . Surprisingly, a recent
      study of KNOX and ARP gene expression in a lycophyte was reported to indicate
      recruitment of a similar mechanism for determinacy in both types of leaves . We
      examined the expression of Class III HD-Zip genes in the lycophyte Selaginella
      kraussiana and in two gymnosperms, Ginkgo and Pseudotsuga. Our data indicate that
      mechanisms promoting leaf initiation, vascularization, and polarity are quite
      different in lycophytes and seed plants, consistent with the hypotheses that
      megaphylls originated as lateral branches whereas microphylls originated as
      tissue outgrowths.

PMID- 17027488
TI  - Somatosensory precision in speech production.
AB  - Speech production is dependent on both auditory and somatosensory feedback.
      Although audition may appear to be the dominant sensory modality in speech
      production, somatosensory information plays a role that extends from brainstem
      responses to cortical control. Accordingly, the motor commands that underlie
      speech movements may have somatosensory as well as auditory goals. Here we
      provide evidence that, independent of the acoustics, somatosensory information is
      central to achieving the precision requirements of speech movements. We were able
      to dissociate auditory and somatosensory feedback by using a robotic device that
      altered the jaw's motion path, and hence proprioception, without affecting speech
      acoustics. The loads were designed to target either the consonant- or vowel
      related portion of an utterance because these are the major sound categories in
      speech. We found that, even in the absence of any effect on the acoustics, with
      learning subjects corrected to an equal extent for both kinds of loads. This
      finding suggests that there are comparable somatosensory precision requirements
      for both kinds of speech sounds. We provide experimental evidence that the neural
      control of stiffness or impedance--the resistance to displacement--provides for
      somatosensory precision in speech production.

PMID- 17027489
TI  - A novel mechanism for the formation of actin-filament bundles by a nonprocessive
      formin.
AB  - Actin-filament bundles (or cables) have a structural role during cell division
      and morphogenesis, but also serve as important "tracks" for the transport of
      materials during cytokinesis and polarized cell growth. However, the dynamic
      formation of these longitudinal actin-filament higher-order structures is not
      understood. Recently, several lines of evidence suggest that formins provide one
      avenue for the initiation of actin cables in vivo. A popular model for the
      mechanism of polymerization of actin filaments by formin involves the processive
      movement of formin attached at the barbed end of an elongating filament. In the
      present study, we use an in vitro system to reconstitute the dynamic formation of
      actin-filament bundles generated by Arabidopsis FORMIN1 (AFH1). To be able to
      visualize individual events in such a complex system, we used real-time
      evanescent-wave microscopy. Surprisingly, we find that AFH1 is a nonprocessive
      formin that moves from the barbed end to the side of an actin filament after the
      nucleation event. We show why this new mechanism of nucleation by a member of the
      formin family is important for bundle formation. Finally, we analyze the
      different parameters controlling the dynamic formation of such longitudinal actin
      filament bundles.

PMID- 17027490
TI  - Generation of specific Ca(2+) signals from Ca(2+) stores and endocytosis by
      differential coupling to messengers.
AB  - It remains unclear how different intracellular stores could interact and be
      recruited by Ca(2+)-releasing messengers to generate agonist-specific Ca(2+)
      signatures. In addition, refilling of acidic stores such as lysosomes and
      secretory granules occurs through endocytosis, but this has never been
      investigated with regard to specific Ca(2+) signatures. In pancreatic acinar
      cells, acetylcholine (ACh), cholecystokinin (CCK), and the messengers cyclic ADP
      ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and
      inositol 1,4,5-trisphosphate (IP(3)) evoke repetitive local Ca(2+) spikes in the
      apical pole. Our work reveals that local Ca(2+) spikes evoked by different
      agonists all require interaction of acid Ca(2+) stores and the endoplasmic
      reticulum (ER), but in different proportions. CCK and ACh recruit Ca(2+) from
      lysosomes and from zymogen granules through different mechanisms; CCK uses NAADP
      and cADPR, respectively, and ACh uses Ca(2+) and IP(3), respectively. Here, we
      provide pharmacological evidence demonstrating that endocytosis is crucial for
      the generation of repetitive local Ca(2+) spikes evoked by the agonists and by
      NAADP and IP(3). We find that cADPR-evoked repetitive local Ca(2+) spikes are
      particularly dependent on the ER. We propose that multiple Ca(2+)-releasing
      messengers determine specific agonist-elicited Ca(2+) signatures by controlling
      the balance among different acidic Ca(2+) stores, endocytosis, and the ER.

PMID- 17027491
TI  - Microtubule-associated AIR9 recognizes the cortical division site at preprophase
      and cell-plate insertion.
AB  - In plants, the preprophase band (PPB) of microtubules marks the cortical site
      where the cross-wall will fuse with the parental wall during cytokinesis . This
      band disappears before metaphase, and it is not known how the division plane is
      "memorized". One idea is that the PPB leaves behind molecules involved in the
      maturation of the cell plate . Here, we report on the proteomic isolation of a
      novel 187 kDa microtubule-associated protein, AIR9, conserved in land plants and
      trypanosomatid parasites. AIR9 decorates cortical microtubules and the PPB but is
      downregulated during mitosis. AIR9 reappears at the former PPB site precisely
      when the cortex is contacted by the outwardly growing cytokinetic apparatus. AIR9
      then moves inward on the new cross-wall and thus forms a torus. Truncation
      studies show that formation of the torus requires a repeated domain separate from
      AIR9's microtubule binding site. Cell plates induced to insert outside the
      predicted division site do not elicit an AIR9 torus, suggesting that AIR9
      recognizes a component of the former PPB. Such misplaced walls remain immature,
      based on their prolonged staining for the cell-plate polymer callose. We propose
      that AIR9 may be part of the mechanism ensuring the maturation of those cell
      plates successfully contacting the "programmed" cortical division site.

PMID- 17027492
TI  - Katanin disrupts the microtubule lattice and increases polymer number in C.
      elegans meiosis.
AB  - Katanin is a heterodimer that exhibits ATP-dependent microtubule-severing
      activity in vitro. In Xenopus egg extracts, katanin activity correlates with the
      addition of cyclin B/cdc2, suggesting a role for microtubule severing in the
      disassembly of long interphase microtubules as the cell prepares for mitosis.
      However, studies from plant cells, cultured neurons, and nematode embryos suggest
      that katanin could be required for the organization or postnucleation processing
      of microtubules, rather than the dissolution of microtubule structures. Here we
      reexamine katanin's role by studying acentrosomal female meiotic spindles in C.
      elegans embryos. In mutant embryos lacking katanin, microtubules form around
      meiotic chromatin but do not organize into bipolar spindles. By using electron
      tomography, we found that katanin converts long microtubule polymers into shorter
      microtubule fragments near meiotic chromatin. We further show that turning on
      katanin during mitosis also creates a large pool of short microtubules near the
      centrosome. Furthermore, the identification of katanin-dependent microtubule
      lattice defects supports a mechanism involving an initial perforation of the
      protofilament wall. Taken together, our data suggest that katanin is used during
      meiotic spindle assembly to increase polymer number from a relatively inefficient
      chromatin-based microtubule nucleation pathway.

PMID- 17027493
TI  - A pheromone that rapidly promotes learning in the newborn.
AB  - Mammalian neonates depend on their mother's food supply and use a defined
      sequence of actions to find her mammary area. Their behavior is initially
      uncertain and demanding but rapidly becomes optimal. Efficient learning is thus
      operating in newborns. For instance, European rabbit (Oryctolagus cuniculus) pups
      localize the nipples through typical orocephalic movements. These movements are
      released by the mammary pheromone secreted in milk or by prenatally learned odor
      cues. During daily nursing, they also learn odors associated with the mother,
      supposedly with sucking as the main reinforcer. We here investigate the role of
      the mammary pheromone as an enforcer of early olfactory learning in newborn
      rabbits. In testing more than 950 pups, we show that the mammary pheromone
      promotes learning of neutral odorants paired with the pheromone in single and
      short trials. The pheromone-induced learning is efficient from birth and supports
      successive acquisition of distinct odorants. This reveals that a mammalian
      pheromone can function as a "cognitive organizer" that promotes early learning of
      relevant environmental cues.

PMID- 17027494
TI  - Mitosis-specific mechanosensing and contractile-protein redistribution control
      cell shape.
AB  - Because cell-division failure is deleterious, promoting tumorigenesis in mammals,
      cells utilize numerous mechanisms to control their cell-cycle progression. Though
      cell division is considered a well-ordered sequence of biochemical events,
      cytokinesis, an inherently mechanical process, must also be mechanically
      controlled to ensure that two equivalent daughter cells are produced with high
      fidelity. Given that cells respond to their mechanical environment, we
      hypothesized that cells utilize mechanosensing and mechanical feedback to sense
      and correct shape asymmetries during cytokinesis. Because the mitotic spindle and
      myosin II are vital to cell division, we explored their roles in responding to
      shape perturbations during cell division. We demonstrate that the contractile
      proteins myosin II and cortexillin I redistribute in response to intrinsic and
      externally induced shape asymmetries. In early cytokinesis, mechanical load
      overrides spindle cues and slows cytokinesis progression while contractile
      proteins accumulate and correct shape asymmetries. In late cytokinesis,
      mechanical perturbation also directs contractile proteins but without apparently
      disrupting cytokinesis. Significantly, this response only occurs during anaphase
      through cytokinesis, does not require microtubules, and is independent of spindle
      orientation, but is dependent on myosin II. Our data provide evidence for a
      mechanosensory system that directs contractile proteins to regulate cell shape
      during mitosis.

PMID- 17027495
TI  - Metaphase arrest by cyclin E-Cdk2 requires the spindle-checkpoint kinase Mps1.
AB  - Cytostatic factor (CSF) arrests vertebrate eggs in metaphase of meiosis II
      through several pathways that inhibit activation of the anaphase-promoting
      complex/cyclosome (APC/C). In Xenopus, the Mos-MEK1-MAPK-p90(Rsk) cascade
      utilizes spindle-assembly-checkpoint components to effect metaphase arrest.
      Another pathway involves cyclin E-Cdk2, and sustained cyclin E-Cdk2 activity in
      egg extracts causes metaphase arrest in the absence of Mos; this latter finding
      suggests that an independent pathway contributes to CSF arrest. Here, we
      demonstrate that metaphase arrest with cyclin E-Cdk2, but not with Mos, requires
      the spindle-checkpoint kinase monopolar spindles 1 (Mps1), a cyclin E-Cdk2 target
      that is also implicated in centrosome duplication. xMps1 is synthesized and
      activated during oocyte maturation and inactivated upon CSF release. In egg
      extracts, CSF release by calcium was inhibited by constitutively active cyclin E
      Cdk2 and delayed by wild-type xMps1. Ablation of cyclin E by antisense
      oligonucleotides blocked accumulation of xMps1, suggesting that cyclin E-Cdk2
      controls Mps1 levels. During meiosis II, activated cyclin E-Cdk2 significantly
      inhibited the APC/C even in the absence of the Mos-MAPK pathway, but this
      inhibition was not sufficient to suppress S phase between meiosis I and II. These
      results uniquely place xMps1 downstream of cyclin E-Cdk2 in mediating a pathway
      of APC/C inhibition and metaphase arrest.

PMID- 17027496
TI  - DNA kinks available...if needed.

PMID- 17027497
TI  - The Role of histidine residues in low-pH-mediated viral membrane fusion.
AB  - A central event in the invasion of a host cell by an enveloped virus is the
      fusion of viral and cell membranes. For many viruses, membrane fusion is driven
      by specific viral surface proteins that undergo large-scale conformational
      rearrangements, triggered by exposure to low pH in the endosome upon
      internalization. Here, we present evidence suggesting that in both class I
      (helical hairpin proteins) and class II (beta-structure-rich proteins) pH
      dependent fusion proteins the protonation of specific histidine residues triggers
      fusion via an analogous molecular mechanism. These histidines are located in the
      vicinity of positively charged residues in the prefusion conformation, and they
      subsequently form salt bridges with negatively charged residues in the postfusion
      conformation. The molecular surfaces involved in the corresponding structural
      rearrangements leading to fusion are highly conserved and thus might provide a
      suitable common target for the design of antivirals, which could be active
      against a diverse range of pathogenic viruses.

PMID- 17027498
TI  - Common evolutionary origin of swapped-hairpin and double-psi beta barrels.
AB  - The core of swapped-hairpin and double-psi beta barrels is formed by duplication
      of a conserved betaalphabeta element, suggesting a common evolutionary origin.
      The path connecting the two folds is unclear as the two barrels are not
      interconvertible by a simple topological modification, such as circular
      permutation. We have identified a protein family whose sequence properties are
      intermediate to the two folds. The structure of one of these proteins, Pyrococcus
      horikoshii PhS018, is also built by duplication of the conserved betaalphabeta
      element but shows yet a third topology, which we name the RIFT barrel. This
      topology is widespread in the structure database and spans three folds of the
      SCOP classification, including the middle domain of EF-Tu and the N domain of F1
      ATPase. We propose that swapped-hairpin beta barrels arose from an ancestral RIFT
      barrel by strand invasion and double-psi beta barrels by a strand swap. We group
      the three barrel types into a metafold, the cradle-loop barrels.

PMID- 17027499
TI  - Assessing computational amino acid beta-turn propensities with a phage-displayed
      combinatorial library and directed evolution.
AB  - Structure propensities of amino acids are important determinants in guiding
      proteins' local and global structure formation. We constructed a phage display
      library--a hexa-HIS tag upstream of a CXXC (X stands for any of the 20 natural
      amino acids) motif appending N-terminal to the minor capsid protein pIII of M13KE
      filamentous phage--and developed a novel directed-evolution procedure to select
      for amino acid sequences forming increasingly stable beta-turns in the disulfide
      bridged CXXC motif. The sequences that emerged from the directed-evolution cycles
      were in good agreement with type II beta-turn propensities derived from surveys
      of known protein structures, in particular, Pro-Gly forming a type II beta-turn.
      The agreement strongly supported the notion that beta-turn formation plays an
      active role in initiating local structure folding in proteins.

PMID- 17027500
TI  - Structures of two bacterial prolyl-tRNA synthetases with and without a cis
      editing domain.
AB  - Prolyl-tRNA synthetases (ProRSs) are unique among synthetases in that they have
      diverse architectures, notably the variable presence of a cis-editing domain
      homologous to the freestanding deacylase proteins YbaK and ProX. Here, we
      describe crystal structures of two bacterial ProRSs from the pathogen
      Enterococcus faecalis, which possesses an editing domain, and from
      Rhodopseudomonas palustris, which does not. We compare the overall structure and
      binding mode of ATP and prolyl-adenylate with those of the archael/eukaryote-type
      ProRS from Thermus thermophilus. Although structurally more homologous to YbaK,
      which preferentially hydrolyzes Cys-tRNA(Pro), the editing domain of E. faecalis
      ProRS possesses key elements similar to ProX, with which it shares the activity
      of hydrolyzing Ala-tRNA(Pro). The structures give insight into the complex
      evolution of ProRSs, the mechanism of editing, and structural differences between
      prokaryotic- and eukaryotic-type ProRSs that can be exploited for antibiotic
      design.

PMID- 17027501
TI  - Kinking occurs during molecular dynamics simulations of small DNA minicircles.
AB  - Recent experiments on minicircle formation suggest that a conformational
      mechanism other than smooth deformation may be playing a role in enhancing DNA
      flexibility. Both local base unpairing and kink formation have been suggested as
      possible explanations. Although kinks within isolated DNA were proposed 30 years
      ago, they have, until now, only been observed within DNA complexed with proteins.
      In order to test how DNA behaves in the strong bending regime, we have carried
      out molecular dynamics simulations of a 94 base pair minicircle in explicit
      solvent with two different linking numbers, corresponding to a torsionally
      relaxed state and a positively supercoiled state. The simulations suggest that
      sharp kinks can indeed arise in small minicircles. The relaxed minicircle is
      generally associated with a single kink, while two kinks occur with the
      supercoiled state. No evidence is seen of base unpaired regions.

PMID- 17027502
TI  - The structures of frataxin oligomers reveal the mechanism for the delivery and
      detoxification of iron.
AB  - Defects in the mitochondrial protein frataxin are responsible for Friedreich
      ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children.
      Here, we present the crystal structures of the iron-free and iron-loaded frataxin
      trimers, and a single-particle electron microscopy reconstruction of a 24 subunit
      oligomer. The structures reveal fundamental aspects of the frataxin mechanism.
      The trimer has a central channel in which one atom of iron binds. Two
      conformations of the channel with different metal-binding affinities suggest that
      a gating mechanism controls whether the bound iron is delivered to other proteins
      or transferred to detoxification sites. The trimer constitutes the basic
      structural unit of the 24 subunit oligomer. The architecture of this oligomer and
      several features of the trimer structure demonstrate striking similarities to the
      iron-storage protein ferritin. The data reveal how stepwise assembly provides
      frataxin with the structural flexibility to perform two functions: metal delivery
      and detoxification.

PMID- 17027503
TI  - Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible
      binding mode.
AB  - Calmodulin regulates ryanodine receptor-mediated Ca(2+) release through a
      conserved binding site. The crystal structure of Ca(2+)-calmodulin bound to this
      conserved site reveals that calmodulin recognizes two hydrophobic anchor residues
      at a novel "1-17" spacing that brings the calmodulin lobes close together but
      prevents them from contacting one another. NMR residual dipolar couplings
      demonstrate that the detailed structure of each lobe is preserved in solution but
      also show that the lobes experience domain motions within the complex. FRET
      measurements confirm the close approach of the lobes in binding the 1-17 target
      and show that calmodulin binds with one lobe to a peptide lacking the second
      anchor. We suggest that calmodulin regulates the Ca(2+) channel by switching
      between the contiguous binding mode seen in our crystal structure and a state
      where one lobe of calmodulin contacts the conserved binding site while the other
      interacts with a noncontiguous site on the channel.

PMID- 17027504
TI  - A potential protein-RNA recognition event along the RISC-loading pathway from the
      structure of A. aeolicus Argonaute with externally bound siRNA.
AB  - Argonaute proteins are key components of the RNA-induced silencing complex
      (RISC). They provide both architectural and catalytic functionalities associated
      with small interfering RNA (siRNA) guide strand recognition and subsequent guide
      strand-mediated cleavage of complementary mRNAs. We report on the 3.0 A crystal
      structures of 22-mer and 26-mer siRNAs bound to Aquifex aeolicus Argonaute (Aa
      Ago), where one 2 nt 3' overhang of the siRNA inserts into a cavity positioned on
      the outer surface of the PAZ-containing lobe of the bilobal Aa-Ago architecture.
      The first overhang nucleotide stacks over a tyrosine ring, while the second
      overhang nucleotide, together with the intervening sugar-phosphate backbone,
      inserts into a preformed surface cavity. Photochemical crosslinking studies on Aa
      Ago with 5-iodoU-labeled single-stranded siRNA and siRNA duplex provide support
      for this externally bound siRNA-Aa-Ago complex. The structure and biochemical
      data together provide insights into a protein-RNA recognition event potentially
      associated with the RISC-loading pathway.

PMID- 17027505
TI  - Ligand-release pathways in the pheromone-binding protein of Bombyx mori.
AB  - Pheromone-binding proteins (PBP) supply olfactory neuron cells with pheromones by
      binding the ligands they are tailored for and carrying them to their receptor.
      The function of a PBP as an efficient carrier requires fast ligand uptake and
      release. The molecular basis of the ligand-binding mechanism was addressed here
      for the intriguing case of the PBP of the silk moth Bombyx mori. This PBP
      completely encapsulates its ligand bombykol without displaying any obvious ligand
      entrance/exit sites. Here, two opposite dissociation routes were identified as
      the most likely entrance/exit paths by replica-exchange molecular dynamics,
      essential dynamics, and force-probe molecular dynamics simulations. One of the
      paths runs along a flexible front lid; the other along the termini at the back.
      Calculated forces and energies suggest that both routes are physiologically
      relevant. The multiplicity of pathways may reduce or tune the entropic barrier
      for ligand binding.

PMID- 17027506
TI  - Pheromone discrimination by the pheromone-binding protein of Bombyx mori.
AB  - Pheromone-binding proteins are postulated to contribute to the exquisite
      specificity of the insect's olfactory system, acting as a filter by
      preferentially binding only one of the components of the natural pheromone. Here,
      we investigated the possible discrimination of the two very similar components of
      the natural pheromone gland from the silk moth, Bombyx mori, bombykol and
      bombykal, by the only pheromone-binding protein (BmorPBP) known to be expressed
      in the pheromone-detecting sensilla. Free-energy calculations and virtual docking
      indicate that both bombykol and bombykal bind to BmorPBP with similar affinity.
      In addition, in vitro competitive binding assays showed that both bombykol and
      bombykal were bound by BmorPBP with nearly the same high affinity. While BmorPBP
      might filter out other physiologically irrelevant compounds hitting the sensillar
      lymph, discrimination between the natural pheromone compounds must be achieved by
      molecular interactions with their cognate receptors.

PMID- 17027507
TI  - Structure of complement component C2A: implications for convertase formation and
      substrate binding.
AB  - C2a provides the catalytic center to the convertase complexes of the classical
      and lectin-binding pathways of complement activation. We determined two crystal
      structures of full-length C2a, with and without a pseudo ligand bound. Both
      structures reveal a near-active conformation of the catalytic center of the
      serine protease domains, while the von Willebrand factor A-type domains display
      an intermediate activation state of helix alpha7 with an open, activated metal
      ion-dependent adhesion site. The open adhesion site likely serves to enhance the
      affinity for the ligand C4b, similar to "inside-out" signaling in integrins.
      Surprisingly, the N-terminal residues of C2a are buried in a crevice near helix
      alpha7, indicative of a structural switch between C2 and C2a. Extended loops on
      the protease domain possibly envelop the protruding anaphylatoxin domain of the
      substrate C3. Together with a putative substrate-induced completion of the
      oxyanion hole, this may contribute to the high substrate specificity of the
      convertases.

PMID- 17027509
TI  - IL-3, IL-5, and GM-CSF signaling: crystal structure of the human beta-common
      receptor.
AB  - The cytokines, interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte
      macrophage colony stimulating factor (GM-CSF), are polypeptide growth factors
      that exhibit overlapping activities in the regulation of hematopoietic cells.
      They appear to be primarily involved in inducible hematopoiesis in response to
      infections and are involved in the pathogenesis of allergic and inflammatory
      diseases and possibly in leukemia. The X-ray structure of the beta common (betac)
      receptor ectodomain has given new insights into the structural biology of
      signaling by IL-3, IL-5, and GM-CSF. This receptor is shared between the three
      ligands and functions together with three ligand-specific alpha-subunits. The
      structure shows betac is an intertwined homodimer in which each chain contains
      four domains with approximate fibronectin type-III topology. The two betac
      subunits that compose the homodimer are interlocked by virtue of the swapping of
      beta-strands between domain 1 of one subunit and domain 3 of the other subunit.
      Site-directed mutagenesis has shown that the interface between domains 1 and 4 in
      this unique structure forms the functional epitope. This epitope is similar to
      those of other members of the cytokine class I receptor family but is novel in
      that it is formed by two different receptor chains. The chapter also reviews
      knowledge on the closely related mouse beta(IL-3) receptor and on the alpha
      subunit-ligand interactions. The knowledge on the two beta receptors is placed in
      context with advances in understanding of the structural biology of other members
      of the cytokine class I receptor family.

PMID- 17027510
TI  - Crystal structures and inhibitors of proteins involved in IL-2 release and T cell
      signaling.

PMID- 17027511
TI  - Structural studies of the interleukin-19 subfamily of cytokines.
AB  - The interleukin-19 (IL-19) subfamily of cytokines is part of a larger family of
      homologs of IL-10 that includes two groups of proteins: five viral cytokines, and
      eight cellular cytokines, having quite different biological activities. Among
      proteins of the latter group, IL-19, IL-20, IL-22, and IL-24 were suggested to
      form a structurally unique IL-19 subfamily characterized by their structural
      features and aggregation state as monomers. IFN-lambda1, IFN-lambda2, and IFN
      lambda3 are likely to belong to this subfamily, and it is still not clear whether
      IL-26 belongs to it or not. In spite of their differences in biological function,
      all cellular homologs of IL-10 used for signaling a set of five overlapping
      membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN
      lambdaR) and two short receptor chains (IL-20R2 and IL-10R2). Signal transduction
      is initiated when a cytokine binds two receptor chains, one long and one short,
      forming a ternary complex. Crystal structures of IL-19 and IL-22 showed that
      these cytokines consist of seven amphipathic helices of different length
      organized in helical bundle, covering an extensive hydrophobic core. Based on the
      similarity of the structures with the structure of a single domain of IL-10, and
      with the crystal structure of a binary IL-10/IL-10R1 complex, putative receptor
      binding sites on the surface of IL-19 and IL-22 were identified. This chapter
      summarizes the available structural data on the IL-19 subfamily of cytokines and
      their putative ligand/receptor complexes.

PMID- 17027512
TI  - Interleukin-22 and its crystal structure.
AB  - Interleukin-22 (IL-22) is a cytokine that regulates the production of acute phase
      proteins of the immunological response. On binding to its cognate receptor (IL
      22R1), which is associated to the interleukin-10 receptor 2 (IL-10R2), IL-22
      promotes activation of signal transducer and activator of transcription (STAT)
      pathway and several other cellular responses. A soluble receptor termed
      interleukin-22 binding protein (IL-22BP) is also able to bind to IL-22 as a
      natural protein antagonist, and probably provides systemic regulation of IL-22
      activity. This inflammatory response system is analyzed here in terms of its
      molecular physiology and structural assembly. Three-dimensional (3D) model of IL
      22 and structural basis of its interactions with the cognate receptors are
      discussed.

PMID- 17027513
TI  - Control of interleukin-2 gene transcription: a paradigm for inducible, tissue
      specific gene expression.
AB  - Interleukin-2 (IL-2) is a key cytokine that controls immune cell function, in
      particular the adaptive arm of the immune system, through its ability to control
      the clonal expansion and homeostasis of peripheral T cells. IL-2 is produced
      almost exclusively by T cells in response to antigenic stimulation and thus
      provides an excellent example of a cell-specific inducible gene. The mechanisms
      that control IL-2 gene transcription have been studied in detail for the past 20
      years and our current understanding of the nature of the inducible and tissue
      specific controls will be discussed.

PMID- 17027514
TI  - Transcription factors mediating interleukin-3 survival signals.
AB  - Interleukin-3 (IL-3) is one of the major hematopoietic cytokines that regulate
      the survival of hematopoietic cells of various lineages. Although the mechanism
      underlying the survival effect of IL-3 has been investigated intensively for more
      than a decade, our knowledge of the survival-signaling network remains
      incomplete. Binding of IL-3 to its cognate receptors initiates rapid tyrosine
      phosphorylation of Janus kinases (JAKs) and of signal transducer and activator of
      transcription (STAT) proteins, as well as activation of the phosphatidylinositol
      3 kinase (PI-3K)/Akt and Ras/Raf/MAPK kinase (MEK)/mitogen-activated protein
      kinase (MAPK) pathways. These signals culminate in induction of a constellation
      of antiapoptotic genes and prevent cell death from occurring. Thus IL-3 signaling
      has substantial effects on kinase activation and gene transcription. Previous
      articles have summarized the roles of these kinase pathways in cell proliferation
      and survival. In this chapter, we will focus on the role of several newly
      characterized transcriptional factors, which are targets of these initial kinase
      cascades and bridge the gap between kinases and survival effector genes, in
      transducing the IL-3 survival signal. The biological significance of the
      existence of these multiple survival-specific transcription pathways will also be
      discussed.

PMID- 17027515
TI  - Interleukins and STAT signaling.
AB  - Metazoan cells secrete small proteins termed cytokines that execute a variety of
      biological functions essential for the survival of organisms. Binding of
      cytokines that belong to the hematopoietin- or interferon-family, to their
      cognate receptors on the surface of target cells, induces receptor aggregation,
      which in turn sequentially triggers tyrosine-phosphorylation-dependent activation
      of receptor-associated Janus-family tyrosine kinases (JAKs), receptors, and
      signal transducers and activators of transcription (STATs). Phosphorylated STATs
      form dimers that migrate to the nucleus, bind to cognate enhancer elements and
      activate transcription of target genes. Each cytokine activates a specific set of
      genes to execute its biological functions with a certain degree of redundancy.
      Cytokine signals are, in general, transient in nature. Therefore, under normal
      physiological conditions, initiation and attenuation of cytokine signals are
      tightly controlled via multiple cellular and molecular mechanisms. Aberrant
      activation of cytokine signaling pathways is, however, found under a variety of
      patho-physiological conditions including cancer and immune diseases.

PMID- 17027516
TI  - The newest interleukins: recent additions to the ever-growing cytokine family.
AB  - Cytokines play a critical role in the control of the innate and adaptive immune
      responses. The most recent additions to the ever-growing family of cytokines
      include interleukin (IL)-27, IL-28A, IL-28B, IL-29, IL-31, IL-32, and IL-33. Many
      of the newly identified cytokines and/or their specific receptors have been
      identified using bioinformatics. The coming of age of this discipline has
      coincided with completion of the sequencing of the human genome thus enabling the
      identification of new uncharacterized proteins. The latest additions to the
      interleukin family have shed new light on the intricacies of immune system
      regulation. These novel cytokines have pleiotrophic actions ranging from
      antiviral immunity to the regulation of Th2 immune responses. For example, the
      discovery of IL-27 has greatly improved our understanding of the factors
      regulating the polarization of the T helper cell responses and IL-31 appears to
      be an important regulator of Th2 responses. On the other hand, IL-28 and IL-29
      are considered to be critical for mounting an efficient antiviral response and IL
      32 and IL-33, which are yet to be fully characterized, are emerging as important
      components of the inflammatory response in allergy and autoimmunity. These new
      cytokine/receptor combinations may therefore serve as novel targets for the
      treatment and control of allergy, autoimmune diseases, and some cancers.

PMID- 17027517
TI  - The interleukin-1 receptor family.
AB  - The cytokines IL-1 and IL-18 are key molecules both in the innate and in the
      adaptive immune response. Their activity is mediated by specific receptors
      present on the membrane of target cells. It has become apparent that these
      receptors are members of a larger family of related receptors, most of which are
      apparently involved in the mechanisms of host defense. Thus, the large Toll/IL-1R
      (TIR) superfamily encompasses the Ig domain family (IL-1 receptors, IL-18
      receptors, and IL-1R-like receptors), the leucine-rich domain family [the Toll
      like receptors (TLR) and similar receptors], and a series of TIR domain
      containing intracellular adapter molecules. The TIR superfamily is defined by a
      common intracellular TIR domain, involved in the initiation of signaling. A group
      of TIR domain-containing adapters (MyD88, TIRAP, TRIF, and TRAM) are
      differentially recruited to the Toll/IL-1 receptors, contributing to the
      specificity of signaling. Recent studies have also begun to unravel the
      mechanisms of negative regulation of the Toll/IL-1 receptors. The orphan receptor
      TIR8/SIGIRR, a member of TIR superfamily, while unable to initiate signaling, can
      negatively modulate the TIR-mediated responses. Other negative regulators of the
      Toll/IL-1R family include T1/ST2, some soluble forms of TLR, and MyD88s. The
      coordinated positive and negative regulation of the TIR activation ensures the
      appropriate modulation of the innate and inflammatory responses and avoids the
      risk of pathological derangement. This chapter will consider in detail the
      characteristics and functional role of the Ig domain receptor subfamily in the
      regulation of host defense and their possible role in pathology.

PMID- 17027518
TI  - The IL-17 cytokine family.
AB  - IL-17A and its receptor are the founding members of a recently described cytokine
      family, with unique sequences and functions in the immune system and elsewhere.
      Consisting of six ligands (IL-17A-F) and five receptors (IL-17RA-IL-17RE) in
      mammals, these molecules have distinct primary amino acid structures with only
      minimal homology to other cytokine families. By far the best studied of these
      cytokines to date are IL-17A and its receptor, IL-17RA. IL-17A is produced
      primarily by T cells, and is the hallmark cytokine of a newly defined T helper
      cell subset that appears to be involved in generation of autoimmunity. Despite
      its production by the adaptive immune system, IL-17A exhibits proinflammatory
      activities similar to innate immune cytokines such as IL-1beta and TNF-alpha and
      appears to play important and nonredundant roles in regulating granulocytes in
      vivo. As a result, IL-17A also plays key roles in host defense. In contrast to
      the restricted expression of IL-17A, the IL-17RA receptor is ubiquitously
      expressed, and thus most cells are potential physiological targets of IL-17A.
      This chapter describes the major molecular properties, biological activities, and
      known signaling pathways of the IL-17 family, with an emphasis on IL-17A and IL
      17RA.

PMID- 17027519
TI  - NF-kappaB and cytokines.
AB  - Cytokines represent a heterogeneous group of soluble mediators which are involved
      in almost any physiological and pathological process. The release of many
      cytokines and numerous of their biological activities are mediated by nuclear
      factor-kappaB (NF-kappaB). NF-kappaB is a ubiquitous transcription factor which
      is crucially involved in many biological processes, including tissue development
      and maintenance of tissue homeostasis. NF-kappaB also controls apoptotic cell
      death of both normal and malignant cells. Thus, it is a challenging target for
      anticancer and anti-inflammatory strategies. However, it has been recognized that
      NF-kappaB does not only influence many biological processes but also under
      certain conditions the activities of NF-kappaB can be altered as well, for
      example, by cytokines. This cross talk needs to be taken into account when
      developing strategies targeting NF-kappaB for anticancer therapy.

PMID- 17027520
TI  - IkappaB-zeta: an inducible regulator of nuclear factor-kappaB.
AB  - The innate immune system responds to various microbial substances to elicit
      production of cytokines, chemokines, and costimulatory molecules that regulate
      activation of the acquired immune system. Although the transcription factor
      nuclear factor (NF)-kappaB plays central roles in the induction, it remains to be
      clarified how appropriate genes are selectively activated with appropriate timing
      and duration by the multifunctional transcription factor after integration of
      signals activated by invasion of various pathogens. IkappaB-zeta is barely
      detectable in resting cells and is strongly induced upon stimulation of the
      innate immune system. The induced IkappaB-zeta associates with the NF-kappaB
      subunit in the nucleus and regulates its transcriptional activity both positively
      and negatively depending on genes. Thus, the innate immune system utilizes NF
      kappaB as a major transcription factor and modulates its activity in a gene
      specific manner by the regulatory factor IkappaB-zeta, which is specifically
      induced upon stimulation of the innate immune system. This multistep regulation
      of the transcription would be fundamental in selective expression of genes upon
      cell activation.

PMID- 17027521
TI  - The inhibitory effects of interleukin-1 on growth hormone action during catabolic
      illness.
AB  - Growth hormone (GH) induces the expression of the anabolic genes responsible for
      growth, metabolism, and differentiation. Normally, GH stimulates the synthesis of
      circulating insulin-like growth factor-I (IGF-I) by liver, which upregulates
      protein synthesis in many tissues. The development of GH resistance during
      catabolic illness or inflammation contributes to loss of body protein, resulting
      in multiple complications that prolong recovery and cause death. In septic
      patients, increased levels of proinflammatory cytokines and GH resistance are
      commonly observed together. Numerous studies have provided evidence that the
      inhibitory effects of cytokines on skeletal muscle protein synthesis during
      sepsis and inflammation are mediated indirectly by changes in the GH/IGF-I
      system. Interleukin (IL)-1, a member of the family of proinflammatory cytokines,
      interacts with most cell types and is an important mediator of the inflammatory
      response. Infusion of a specific IL-1 receptor antagonist (IL-1Ra) ameliorates
      protein catabolism and GH resistance during systemic infection. This suggests
      that IL-1 is an important mediator of GH resistance during systemic infection or
      inflammation. Consequently, a better understanding of the interaction between GH,
      IL-1, and the regulation of protein metabolism is of great importance for the
      care of the patient.

PMID- 17027522
TI  - The role of the interleukin-6/gp130 signaling pathway in bone metabolism.

PMID- 17027523
TI  - Regulation of osteoclast differentiation and function by interleukin-1.
AB  - Interleukin-1 (IL-1) is a multifunctional cytokine that regulates various
      cellular and tissue functions. Among tissues, bone is the most sensitive to IL-1.
      IL-1 is a potent cytokine for bone resorption and participates in the multiple
      steps of osteoclast recruitment, such as differentiation, multinucleation,
      activation, and survival. On the other hand, considerable evidence has been
      accumulated over the past 10 years to indicate that this cytokine plays key roles
      in pathological bone destruction in a variety of human diseases, including
      rheumatoid arthritis, osteoporosis, and periodontal disease. In this chapter, we
      review the history of "IL-1 in bone" and the locus of this cytokine "from
      laboratory bench to bedside." A better understanding of the role of IL-1 in
      osteoclastic bone resorption would provide opportunities for developing new
      therapeutics to treat diseases of the bone.

PMID- 17027524
TI  - The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation.
AB  - Interleukin (IL)-1 is a cytokine that plays a major role in inflammatory
      responses in the context of infections and immune-mediated diseases. IL-1 refers
      to two different cytokines, termed IL-1alpha and IL-1beta, produced from two
      genes. IL-1alpha and IL-1beta are produced by different cell types following
      stimulation by bacterial products, cytokines, and immune complexes.
      Monocytes/macrophages are the primary source of IL-1beta. Both cytokines do not
      possess leader peptide sequences and do not follow a classical secretory pathway.
      IL-1alpha is mainly cell associated, whereas IL-1beta can be released from
      activated cells after cleavage of its amino-terminal region by caspase-1. IL-1 is
      present in the synovial tissue and fluids of patients with rheumatoid arthritis.
      Several in vitro studies have shown that IL-1 stimulates the production of
      mediators such as prostaglandin E(2), nitric oxide, cytokines, chemokines, and
      adhesion molecules that are involved in articular inflammation. Furthermore, IL-1
      stimulates the synthesis and activity of matrix metalloproteinases and other
      enzymes involved in cartilage destruction in rheumatoid arthritis and
      osteoarthritis. The effects of IL-1 are inhibited in vitro and in vivo by natural
      inhibitors such as IL-1 receptor antagonist and soluble receptors. IL-1 receptor
      antagonist belongs to the IL-1 family of cytokines and binds to IL-1 receptors
      but does not induce any intracellular response. IL-1 receptor antagonist inhibits
      the effect of IL-1 by blocking its interaction with cell surface receptors. The
      use of IL-1 inhibitors in experimental models of inflammatory arthritis and
      osteoarthritis has provided a strong support for the role of IL-1 in the
      pathogeny of these diseases. Most importantly, these findings have been confirmed
      in clinical trials in patients with rheumatic diseases. Additional strategies
      aimed to block the effect of IL-1 are tested in clinical trials.

PMID- 17027525
TI  - Cytokines in type 2 diabetes.

PMID- 17027526
TI  - Release of interleukins and other inflammatory cytokines by human adipose tissue
      is enhanced in obesity and primarily due to the nonfat cells.
AB  - The white adipose tissue, especially of humans, is now recognized as the central
      player in the mild inflammatory state that is characteristic of obesity. The
      question is how the increased accumulation of lipid seen in obesity causes an
      inflammatory state and how this is linked to the hypertension and type 2 diabetes
      that accompanies obesity. Once it was thought that adipose tissue was primarily a
      reservoir for excess calories that were stored in the adipocytes as
      triacylglycerols. In times of caloric deprivation these stored lipids were
      mobilized as free fatty acids and the insulin resistance of obesity was
      attributed to free fatty acids. It is now clear that in humans the expansion of
      adipose tissue seen in obesity results in more blood vessels, more connective
      tissue fibroblasts, and especially more macrophages. There is an enhanced
      secretion of some interleukins and inflammatory cytokines in adipose tissue of
      the obese as well as increased circulating levels of many cytokines. The central
      theme of this chapter is that human adipose tissue is a potent source of
      inflammatory interleukins plus other cytokines and that the majority of this
      release is due to the nonfat cells in the adipose tissue except for leptin and
      adiponectin that are primarily secreted by adipocytes. Human adipocytes secrete
      at least as much plasminogen activator inhibitor-1 (PAI-1), MCP-1, interleukin-8
      (IL-8), and IL-6 in vitro as they do leptin but the nonfat cells of adipose
      tissue secrete even more of these proteins. The secretion of leptin, on the other
      hand, by the nonfat cells is negligible. The amount of serum amyloid A proteins 1
      & 2 (SAA 1 & 2), haptoglobin, nerve growth factor (NGF), macrophage migration
      inhibitory factor (MIF), and PAI-1 secreted by the adipocytes derived from a gram
      of adipose tissue is 144%, 75%, 72%, 37%, and 23%, respectively, of that by the
      nonfat cells derived from the same amount of human adipose tissue. However, the
      release of IL-8, MCP-1, vascular endothelial growth factor (VEGF), TGF-beta1, IL
      6, PGE(2), TNF-alpha, cathepsin S, hepatocyte growth factor (HGF), IL-1beta, IL
      10, resistin, C-reactive protein (CRP), and interleukin-1 receptor antagonist (IL
      1Ra) by adipocytes is less than 12% of that by the nonfat cells present in human
      adipose tissue. Obesity markedly elevates the total release of TNF-alpha, IL-6,
      and IL-8 by adipose tissue but only that of TNF-alpha is enhanced in adipocytes.
      However, on a quantitative basis the vast majority of the TNF-alpha comes from
      the nonfat cells. Visceral adipose tissue also releases more VEGF, resistin, IL
      6, PAI-1, TGF-beta1, IL-8, and IL-10 per gram of tissue than does abdominal
      subcutaneous adipose tissue. In conclusion, there is an increasing recognition
      that adipose tissue is an endocrine organ that secretes leptin and adiponectin
      along with a host of other paracrine and endocrine factors in addition to free
      fatty acids.

PMID- 17027527
TI  - Role of interleukin-13 in cancer, pulmonary fibrosis, and other T(H)2-type
      diseases.
AB  - Interleukin (IL)-13 plays a major role in various inflammatory diseases including
      cancer, asthma, and allergy. It mediates a variety of different effects on
      various cell types including B cells, monocytes, natural killer cells,
      endothelial cells, and fibroblasts. IL-13 binds to two primary receptor chains IL
      13Ralpha1 and IL-13Ralpha2. The IL-13Ralpha2 but not IL-13Ralpha1 chain binds IL
      13 with high affinity and is overexpressed in a variety of human cancer cells
      derived from glioma, squamous cell carcinoma of head and neck, and AIDS
      associated Kaposi's sarcoma. We have also demonstrated that IL-13Ralpha2
      expression is greatly increased in lung cells when mice were challenged
      intranasally with bleomycin or Aspergillus fumigatus. In addition, IL-13Ralpha2
      increased in surgical lung biopsies from patients with usual interstitial
      pneumonia, nonspecific interstitial pneumonia, and respiratory bronchiolitic
      interstitial pneumonia of unknown origin. Based on various studies, it is
      concluded that IL-13Ralpha2-expressing cells are involved in various pulmonary
      pathological conditions. In contrast, normal tissues such as brain, lung,
      endothelial cells, and head and neck tissues express IL-13Ralpha1 chain, but show
      only marginal expression of IL-13Ralpha2 chain. Thus, IL-13Ralpha2 chain may
      serve as a novel biomarker for diseased cells such as cancer or fibrosis and a
      target for receptor-directed therapeutic agents. To target IL-13R, a recombinant
      fusion protein composed of IL-13 and a derivative of Pseudomonas exotoxin (PE)
      has been produced. This cytotoxin termed as IL-13PE38QQR or IL-13PE38, or IL-13PE
      is highly and specifically cytotoxic to a variety of human tumor cell lines. In
      preclinical models of human glioblastoma, head and neck and AIDS-associated
      Kaposi's cancer, IL-13PE has been found to have significant antitumor activity at
      a tolerated dose. Several phase I clinical trials have been completed in patients
      with recurrent malignant glioma. Recently a phase III clinical trial (PRECISE) in
      patients with recurrent malignant glioma has been completed recruiting a total of
      294 patients. IL-13PE cytotoxin has also shown a significant therapeutic effect
      in preclinical bleomycin or A. fumigatus or Schistosoma mansoni-induced pulmonary
      pathology including granulomatous fibrosis in mouse models. A clinical study in
      these diseases has yet to be initiated.

PMID- 17027528
TI  - Interleukins, inflammation, and mechanisms of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common progressive neurodegenerative form of
      dementia in the elderly and is characterized neuropathologically by
      neurofibrillary tangles (NFT), amyloid neuritic plaques (NP), and prominent
      synaptic and eventually neuronal loss. Although the molecular basis of AD is not
      clearly understood, a neuroinflammatory process, triggered by Abeta42, plays a
      central role in the neurodegenerative process. This inflammatory process is
      driven by activated microglia, astrocytes and the induction of proinflammatory
      molecules and related signaling pathways, leading to both synaptic and neuronal
      damage as well as further inflammatory cell activation. Epidemiologic data as
      well as clinical trial evidence suggest that nonsteroidal anti-inflammatory drug
      (NSAID) use may decrease the incidence of AD, further supporting a role for
      inflammation in AD pathogenesis. Although the precise molecular and cellular
      relationship between AD and inflammation remains unclear, interleukins and
      cytokines might induce activation of signaling pathways leading to futher
      inflammation and neuronal injury. This chapter will discuss the association
      between interleukins and neurodegeneration in AD and highlight the significance
      of genetic and clinical aspects of interleukins in disease expression and
      progression. As part of an emerging inflammatory signaling network underlying AD
      pathogenesis, beta-amyloid (Abeta) stimulates the glial and microglial production
      of interleukins and other cytokines, leading to an ongoing inflammatory cascade
      and contributing to synaptic dysfunction and loss, and later, neuronal death.
      Inflammatory pathways involving interleukin and cytokine signaling might suggest
      potential targets for intervention and influence the development of novel
      therapies to circumvent synaptic and neuronal dysfunction ultimately leading to
      AD neurodegeneration.

PMID- 17027529
TI  - Interleukin-2: from T cell growth and homeostasis to immune reconstitution of HIV
      patients.
AB  - Interleukin (IL)-2 was initially described as a major stimulant of T lymphocytes
      in vitro. Later, the characterization of IL-2 knockout animals showed that the
      ability to stimulate T cells could be replaced by other cytokines. In vivo, IL-2
      plays a unique role in controlling lymphoproliferation. This is partly explained
      by its role in the generation and maintenance of T regulatory cells (Treg). In
      HIV-infected patients, the IL-2/IL-2 receptor (IL-2R) system is dysregulated. The
      fact that IL-2 is underproduced along with defective IL-2R signaling detected in
      patient lymphocytes, may explain the progressive impairment of the immune system
      that occurs during chronic infection with this virus. These defects are partly
      reversed by highly active antiretroviral therapy (HAART). However, in some
      patients IL-2R defects persist and the CD4 counts remain low despite good control
      of the viral load. These patients benefit from HAART given in conjunction with IL
      2 therapy.

PMID- 17027530
TI  - Asthma end points and outcomes: what have we learned?
AB  - In spite of the wide prevalence of asthma and its substantial consequences, the
      diagnosis and assessment of asthma has not been standardized, and the goals of
      therapy currently are not being achieved. Our purpose is to help delineate what
      the most important asthma end points are and what kinds of strategies we should
      use to guide therapy. Comparison of numerous studies reveals that asthma measures
      used routinely in the clinic, such as spirometric lung function, do not uniformly
      correlate with asthma control. We cannot improve outcomes until we determine
      which measures reveal the underlying disease process most clearly and at the same
      time offer ease of performance during routine office visits. We propose that by
      standardizing the way we collect and analyze data from our daily practice, we can
      better define which measures reflect true asthma control. Such measures most
      likely address a spectrum of changes occurring in the pathophysiology of asthma,
      notably distal airway inflammation and hyperresponsiveness. Inflammation may
      provide the best opportunity for assessment and treatment, because if it is
      adequately addressed, airway sensitivity may improve, thereby reducing airway
      obstruction and subsequently minimizing exacerbations. The fraction of exhaled
      nitric oxide as a measure of inflammation is suggested as offering the best
      combination of disease evaluation and practical implementation for improved
      asthma outcomes.

PMID- 17027531
TI  - Effectiveness of community-based injury prevention. Long-term injury rate levels,
      changes, and trends for 14 Swedish WHO-designated Safe Communities.
AB  - This study investigates the injury rate levels, changes, and trends between 1987
      and 2002 for the 14 Swedish municipalities designated as WHO Safe Communities.
      The injury rate was defined as the number of injured patients discharged from
      hospital per 1000 persons. Injury rates were age standardised. Each municipality
      was compared with its respective municipality group, according to a
      classification of Sweden's 288 municipalities into nine groups based on numerous
      structural parameters. The average injury rate levels for the 14 WHO-designated
      Safe Community municipalities ranged from 11.54 to 19.09 per 1000 population
      during the study period, which was defined as the time period during which a
      municipality's injury prevention program has been operational. Eleven of 14
      municipalities had higher levels than their corresponding municipality groups.
      Five of the 14 municipalities "outperformed" their respective municipality groups
      and achieved a greater relative injury rate decrease during the study period. The
      trends for the 14 municipalities in relation to their municipality groups showed
      an inconsistent pattern, with only four municipalities exhibiting overall
      favourable trends for the study period.

PMID- 17027532
TI  - Photocatalytic paper from colloidal TiO(2)--fact or fantasy.
AB  - Photocatalytic paper encompasses a range of materials based on paper and nonwoven
      fabrics which performs a function based on the light-activated catalytic activity
      of colloidal TiO(2). The literature describing photocatalytic paper is surveyed,
      including mechanisms, applications, limitations and future opportunities. The
      technology is in its infancy with less than 10 patents and as many scientific
      publications appearing over the last decade. The main applications described are
      the destruction of organic molecules (mineralization) and photo-disinfection
      (sterilization). These disclosures build upon a much larger literature describing
      photochemical properties of TiO(2) both supported on non-cellulose substrates or
      simply as suspended particles in water or air. Current photocatalytic paper
      developments include methods to fix TiO(2) to cellulose substrates to minimize
      photochemical damage to the paper. Another theme is the use of multiple
      approaches, such as zeolites, for enhanced mineralization, and metals, such as
      silver and copper, for enhanced photocatalytic disinfection.

PMID- 17027533
TI  - Ninety-day mortality after bilateral hip arthroplasty.
AB  - Despite lack of any studies, to our knowledge, bilateral total hip arthroplasty
      (THA) is believed to carry higher perioperative mortality. The purpose of this
      study is to investigate the incidence of mortality within 90 days of bilateral
      THA in a major urban medical center. The incidence of 90-day mortality after 1
      stage bilateral THA performed in 707 patients between 1995 and 2004 was
      evaluated. A detailed analysis of our database was performed to determine which
      bilateral THA patients died within 90 days of surgery. Every living patient who
      had undergone bilateral hip arthroplasty was contacted. One patient (0.14%,
      1/707) died within 90 days of 1-stage bilateral THA. The patient developed
      spontaneous retroperitoneal hematoma requiring massive transfusion. The patient
      died of multisystem failure 35 days after undergoing bilateral THA. One-stage
      bilateral uncemented THA performed in a select group of healthy and young
      patients carries an acceptable risk.

PMID- 17027534
TI  - Steady-state penetration rates of electron beam-irradiated, highly cross-linked
      polyethylene at an average 45-month follow-up.
AB  - Steady-state penetration rates were determined on 53 total hip arthroplasties
      with a minimum 3-year follow-up using electron beam highly cross-linked melted
      polyethylene by determining the femoral head penetration occurring after the
      first year in vivo. These data were compared with that of a matched control
      group. The average steady-state penetration rate of the control group was 144 +/-
      191 mum/y, significantly higher than that of the highly cross-linked polyethylene
      group, 25 +/- 99 microm/y (P = .0001). Linear regression analysis indicated that
      the magnitude of femoral head penetration did not increase with time in the cross
      linked groups. Also, no significant difference existed between the steady-state
      wear rates of the highly cross-linked groups with two head sizes (28 vs 32 mm, P
      = .39).

PMID- 17027535
TI  - Wear of highly cross-linked polyethylene acetabular cup in Japan.
AB  - The wear characteristics of ultra-high-molecular-weight polyethylene acetabular
      cups irradiated with 6.0 to 7.5 Gy of gamma-irradiation were studied in a hip
      simulator and in vivo in 70 hips for 6 to 39 months. The linear wear was 2.5% to
      4.5% of the wear seen in conventional polyethylene cups. A biphasic wear pattern
      was observed over time with a relatively large wear in the first year and a
      subsequent leveling of the wear rate curve. The linear wear rate in the second
      phase (steady state) was 0.006 mm/y. The extent of decrease in clinical wear of
      6.0-Mrad polyethylene (Aeonian, Kyocera Corp, Kyoto, Japan) cups is comparable
      with the decrease of the in vitro wear measured by the hip simulation test.

PMID- 17027536
TI  - Treatment of medial compartment arthritis of the knee: a survey of the American
      Association of Hip and Knee Surgeons.
AB  - Medial compartmental arthritis of the knee is a common orthopedic problem. This
      study surveyed active members of the American Association of Hip and Knee
      Surgeons on recommended surgical treatment of this condition. A response rate of
      30.8% was obtained. One third of respondents (32.9%) reported patient age as the
      most important factor in determining surgical treatment. Total knee arthroplasty
      (89.2%) and arthroscopy (87.2%) were the most widely reported surgical
      treatments. Most respondents (73.7%) rated experience as the primary basis in
      determining factors for surgical recommendations. Case scenarios revealed age and
      gender having significant bearing on treatment recommendations. These results
      suggest that age and degree of deformity are 2 important considerations in
      surgical treatment of medial compartment arthritis and, among this group of
      respondents, influence the wide variety of treatment options.

PMID- 17027537
TI  - Comparison between hand rasping and robotic milling for stem implantation in
      cementless total hip arthroplasty.
AB  - We evaluated the effects of conventional hand rasping and robotic milling on the
      clinical and radiographic results of cementless total hip arthroplasty, with the
      same computed tomography (CT)-based 3-dimensional preoperative planning using a
      ROBODOC workstation (Integrated Surgical Systems, Davis, Calif). The robotic
      milling group consisted of 78 hips, and the hand-rasping group 78 hips. The
      radiographic findings from the preoperative planning and postoperative CT data
      were evaluated using the most accurate CT images reconstructed by the ROBODOC
      workstation. The robotic milling group showed significant superior Merle
      D'Aubigne hip score at 2 years. In the robotic milling group, there were no
      intraoperative femoral fractures, and a radiographically superior implant fit was
      obtained. Hand rasping had the potential to cause intraoperative femoral
      fractures, undersizing of the stem, unexpectedly higher vertical seating, and
      unexpected femoral anteversion causing inferior implant fit.

PMID- 17027538
TI  - Long-term results of the cementless ALLOCLASSIC hip arthroplasty system using a
      28-mm ceramic head: with a retrospective comparison to a 32-mm head.
AB  - One hundred twenty-four total hip arthroplasties in 119 patients, all performed
      with the cementless ALLOCLASSIC hip arthroplasty system (SL stem and CSF cup;
      Centerpulse, Winterthur, Switzerland), were analyzed retrospectively. In all
      hips, a 28-mm head and an ultrahigh-molecular-weight polyethylene inlay were
      used. Of the 124 hips, 81 could be investigated clinically and radiologically
      after an average of 150.6 months (range, 133-169 months). Twenty-six patients (26
      hips) died in the interim. One of these patients had septic cup loosening.
      Seventeen hips (16 patients) were not available for follow-up because of health
      reasons (12 hips in 11 patients), lack of cooperation (3 hips in 3 patients), or
      loss to follow-up (2 hips in 2 patients). Of the 124 total hip arthroplasties, 4
      cups were removed (2 aseptic and 2 septic loosening). No stem had to be removed.
      If aseptic loosening is defined as the end point, the survival rate is 98.4% (95%
      confidence interval, 93.8%-99.6%) for the cup and 100% for the stem after 157
      months. If revision for any reason is defined as the end point, the survival rate
      is 95.6% (95% confidence interval, 90.1%-98.3%). Before operation, the average
      Harris Hip Score was 36.4 points (21-46). At time of follow-up, the average
      Harris Hip Score was 89.7 points (54-100). Radiolucent lines and osteolyses were
      found only seldom (mostly in the proximal stem zones).

PMID- 17027539
TI  - Five-year follow-up of socket movements and loosening after revision with
      impacted morselized allograft bone and cement: a radiostereometric and
      radiographic analysis.
AB  - In 1999, we reported on the 2-year results of a series of 21 first-time socket
      revisions using impacted morselized allograft bone. Seven still migrated between
      1.5 and 2 years. Seventeen remained for the current 5-year follow-up. No socket
      had been rerevised. Five sockets showed signs of radiographic loosening. These 5
      cases also exhibited radiographic signs of allograft resorption as well as high
      rates of socket migration and rotation as measured by radiostereometric analysis.
      Of the 6 remaining sockets that had migrated between 1.5 and 2 years, 3
      stabilized and 3 were among those with signs of radiographic loosening. Fifteen
      patients (15 hips) revealed pain reduction at the 5-year follow-up. Three had
      slight pain on walking that disappeared immediately at rest (pain score 4). All
      the others revealed either no pain (pain score 6) or slight pain that disappeared
      with activity (pain score 5). No pattern of early socket migration according to
      radiostereometric analysis could be identified, predicting later socket migration
      or loosening. The rate of cases with signs of radiographic loosening (29%, 5/17)
      was comparable to that reported by the Nijmegen group but the follow-up was
      shorter in the current study. The rate of cases with signs of radiographic
      loosening was comparable to both conventionally cemented socket revisions and
      cementless revisions. The future will show if further sockets loosen and if the
      loose sockets up to date will end up in rerevisions.

PMID- 17027540
TI  - Comparative flexion after rotating-platform vs fixed-bearing total knee
      arthroplasty.
AB  - A retrospective review of rotating-platform (n = 113) and fixed-bearing (n = 100)
      total knee arthroplasties at a minimum 2-year follow-up was performed. All
      patients in both groups in this study had osteoarthritis and underwent surgery by
      1 of the 2 senior authors at 1 of 2 institutions. A cruciate-retaining total knee
      arthroplasty was implanted with patellar resurfacing in all cases. The only
      difference between the 2 groups was the design of the tibial bearing and its
      tibial tray. Through minimization of confounding variables relating to pathology,
      surgeon, institution, soft-tissue balancing, and type of prosthesis, this study
      isolates articular design as a variable. We could not demonstrate any significant
      difference in knee flexion after either fixed-bearing or rotating-platform
      cruciate-retaining total knee arthroplasty.

PMID- 17027541
TI  - Polyethylene liner exchange of the Harris-Galante porous I and II acetabular
      components without cement: results and complications.
AB  - This study reviewed the long-term efficacy of the locking mechanism of the Harris
      Galante porous (HGP) I and II acetabular components and the results and
      complications of polyethylene liner exchange without cement. There were 400 HGP-I
      components with a mean follow-up of 10 years (range, 2-19 years) and 78 HGP-II
      components with 8 years of mean follow-up (range, 2-13 years). There has been
      only 1 liner dislodgement (0.2%). Thirty-five hips (34 patients) have undergone
      liner exchange without cement. The index acetabular component was implanted as a
      primary procedure in 19 hips and a revision in 16 hips. No exchanged liner has
      dislodged at a mean follow-up time of 5.1 years (range, 2-11 years). However,
      there have been 7 patients (20%) with recurrent dislocation and all required
      reoperation. Dislocation was significantly lower when an elevated rim liner was
      used.

PMID- 17027542
TI  - Patients' outcome after total hip arthroplasty: a comparison between the Western
      Ontario and McMaster Universities index and the Oxford 12-item hip score.
AB  - This prospective cohort study included 402 patients who had primary total hip
      arthroplasty. The Western Ontario and McMaster Universities Index (WOMAC) and the
      Oxford 12-item Hip Score (OHS) were used to assess patients preoperatively and at
      1 year postoperation. The OHS has a higher responsiveness than the WOMAC in the
      global scale and in the pain subscale. However, the WOMAC has better
      responsiveness in its function scale. The point estimate of relative precision of
      measuring postoperative quality of life shows that the OHS has a tendency toward
      a better performance than the WOMAC; however, this finding is not statistically
      significant. The OHS also demonstrates similar floor and ceiling effect patterns
      as does the WOMAC. We recommend that the choice should depend on which scale
      researchers are using to power a study.

PMID- 17027543
TI  - In vivo oxidation of retrieved cross-linked ultra-high-molecular-weight
      polyethylene acetabular components with residual free radicals.
AB  - Wear of ultra-high-molecular-weight polyethylene (UHMWPE) contributes to debris
      that can lead to periprosthetic osteolysis in total hip arthroplasty. Irradiation
      not only decreases wear of UHMWPE but also generates residual free radicals that
      can oxidize the UHMWPE in the long term. Melting or annealing is used to quench
      the free radicals. Melting is more effective than annealing. We hypothesized that
      the postirradiation annealed UHMWPE components would oxidize in vivo and that
      postirradiation melted ones would not. We analyzed surgical explants of UHMWPE
      acetabular liners. The irradiated and annealed explants showed embrittlement,
      oxidation, and an increase in crystallinity. The irradiated and melted UHMWPE
      explants showed no oxidation, no increase in crystallinity, and no embrittlement.
      To prevent long-term chemical changes in highly cross-linked UHMWPE components,
      the residual free radicals must be stabilized after irradiation, preferably by
      melting and not annealing.

PMID- 17027544
TI  - Midterm results of primary total knee arthroplasty using a dished polyethylene
      insert with a recessed or resected posterior cruciate ligament.
AB  - Use of a dished polyethylene insert in 114 total knee arthroplasties, all with
      the posterior cruciate ligament resected or recessed, was retrospectively
      studied. Patients were evaluated at a mean follow-up of 8.3 years. Mean range of
      motion increased from 92 degrees to 111 degrees . Mean Knee Society pain and
      function scores increased from 35.2 and 39.7 to 91.3 and 74.7, respectively.
      WOMAC scores improved significantly in each category evaluated, including pain,
      stiffness, and physical function. Kaplan-Meier survivorship was 95% at 10 years
      (95% confidence interval, 82%-99%). The use of a dished polyethylene insert in
      primary total knee arthroplasty provides good to excellent midterm results
      regardless of whether the posterior cruciate ligament is recessed or sacrificed.

PMID- 17027545
TI  - Lateral patellar contact after total knee arthroplasty: an analysis of the
      effects on postoperative pain and outcome.
AB  - Although medialization of the patellar component during primary total knee
      arthroplasty (TKA) has been advocated for biomechanical reasons, this can lead to
      lateral patellar contact with the femoral component. Using blinded radiographic
      evaluations, we evaluated 980 consecutive primary TKAs performed from 1997 to
      1998. The prevalence of lateral patellar contact in this series was found to be
      46.1%. Lateral patellar contact was not correlated with significant differences
      in our measures of outcome (knee score [P = .1066], functional score [P = .2457],
      or range of motion [P = .2514]). The average pain score in knees with lateral
      patellar contact was higher (48.1) (less pain) when compared with knees without
      (46.7). Total knee arthroplasties without lateral patellar contact had a 1.61
      times odds of experiencing postoperative pain compared with those TKAs with
      lateral patellar contact (P = .0025).

PMID- 17027546
TI  - Ten-year results of ALIZE acetabular cup with hydroxyapatite coating and AURA
      hydroxyapatite-coated stem in total hip arthroplasty.
AB  - One hundred seven total hip arthroplasties were done between 1991 and 1992 with
      ALIZE acetabular cup with hydroxyapatite coating (Biomet France, Valence, France)
      and AURA hydroxyapatite-coated stem (Biomet France) in 107 patients. The
      articulation was ceramic on polyethylene for 102 patients and metal on
      polyethylene for the remaining 5 patients. The mean follow-up of the series was
      8.4 +/- 2.5 years. The mean preoperative Merle d'Aubigne hip functional score was
      10.6 +/- 3 vs 15.8 +/- 1.8 at the latest follow-up. Sixty-three patients were
      alive for the long-term follow-up at a mean of 9.67 +/- 0.25 years. Of the
      patients, 98.5% were satisfied or very satisfied at the latest follow-up. Five
      revisions were documented in these series: 1 for acetabular loosening, 2 for
      traumatic ceramic head fracture, 1 for polyethylene replacement, and 1 for stem
      replacement due to bone fracture. The mean wear rate was 0.076 +/- 0.043 mm/y
      (<0.1 mm/y considered as the normal wear rate). The overall survival rate at 10
      years was 95.6% +/- 2.1% using revision of either component as the end point.

PMID- 17027547
TI  - Outcome of the contralateral hip in rapidly destructive arthrosis after total hip
      arthroplasty: a preliminary report.
AB  - We investigated the outcome of the contralateral hip in patients with rapidly
      destructive arthrosis of the hip after total hip arthroplasty. Twenty-four
      patients were included, and the mean duration of radiographic follow-up was 7.0
      years (range, 3.8-17.8 years). To assess the capable parameters for predicting
      the development of osteoarthritis, we evaluated the receiver operating
      characteristic curves. Three (12.5%) of 24 patients developed osteoarthritis and
      underwent total hip arthroplasty within 3.8 to 6.5 years. In these 3 patients,
      both the acetabular-head index and the center-edge angle were significantly lower
      than those in patients without osteoarthritis (P < .005). Based on the receiver
      operating characteristic curves, both an acetabular-head index of less than 72%
      and a center-edge angle of less than 16 degrees were considered to be associated
      with the development of osteoarthritis.

PMID- 17027548
TI  - Influence of polyethylene constraint on tibial component fixation in total knee
      arthroplasty: follow-up report after 5 years.
AB  - The influence of articulating surface design of AMK total knee prosthesis (DePuy,
      Johnson & Johnson) on migration and radiographic outcome at 5 years was
      evaluated. The knees were randomly allocated to receive a flat or a concave
      insert with retention of the posterior cruciate ligament when preoperative
      deformity was less severe and either a concave or a posterior-stabilized insert
      with resection of the posterior cruciate ligament when deformity was more
      pronounced. In 64 knees, migration was measured with radiostereometry. The
      posterior-stabilized component displayed more varus-valgus tilting than the
      concave insert. Other statistically significant differences in migration were not
      seen. Radiolucent lines were frequently seen without differences between
      prosthesis groups.

PMID- 17027549
TI  - Less invasive total hip arthroplasty: description of a new technique.
AB  - We describe a new technique and aim to justify its use in total hip arthroplasty.
      The incision is short and there is minimal soft tissue dissection: piriformis and
      most of quadratus femoris remain intact. A meticulous capsular repair is
      performed. Patients are mobilized without restrictions. One hundred total hip
      arthroplasties by the standard posterior approach (group 1) were compared with
      100 by the less invasive approach (group 2). Minimum follow-up was 2 years. Mean
      blood loss in group 1 was higher (P < .0001) and inpatient stay longer (P <
      .0001). There was greater improvement in WOMAC scores for up to 1 year in the
      less invasive group (P = .027). In conclusion, the less invasive approach is safe
      and the functional benefits last up to 1 year.

PMID- 17027550
TI  - Predicting pain after total knee arthroplasty.
AB  - Six hundred twenty-two primary total knee arthroplasties were studied
      prospectively in 512 patients. A group with no pain and one with severe pain at 5
      years were statistically compared. The following were significant predictors of
      poor pain outcomes: age below 60 (17%) compared with above 60 (7%, P < .05). The
      first knee was most likely to be in the poor outcome group (13%) compared with
      the second knee (6%). In contrast, patients who underwent simultaneous bilateral
      arthroplasty faired better (2%, P < .01). Performing lateral release and
      sacrificing the posterior cruciate ligament also significantly predicted for poor
      pain outcomes but may have been influenced by selection bias. We conclude that
      avoiding surgery in patients younger than 60 and choosing a simultaneous approach
      to bilateral disease reduce the chance of poor pain outcomes.

PMID- 17027551
TI  - Polished vs rough femoral components in grade A and grade C-2 cement mantles.
AB  - The ideal surface for cemented femoral components remains controversial. Six
      polished stems were compared with 6 rough stems both with good cement mantle and
      also with poor cement mantles in a stair-climbing model. With good cement
      mantles, both the polished and the rough stems were loose by 6 million cycles.
      However, none were loose by radiographic criteria. With the poor cement mantle,
      both stems became loose earlier and developed more micromotion, the polished
      stems having significantly higher and earlier motion than the rough. Radiographic
      evidence of debonding was not visible until the stems had motion of more than
      2,000 microm. In the presence of a good cement mantle in this laboratory model
      there was no significant difference in the development of micromotion under
      fatigue stair-climbing conditions between a polished or grit-blasted femoral
      component. However, in the presence of a poor cement mantle, the polished
      components had earlier and higher micromotion. This study reinforces the
      importance of centralization and cement technique, particularly if using a
      polished surface finish.

PMID- 17027552
TI  - A clinical, radiographic, and cost comparison of cerclage techniques: wires vs
      cables.
AB  - The cerclage technique is used to secure femoral fractures, allografts, and
      plates. It is not clear whether wires or cables are better suited for this
      technique. A retrospective radiographic review of the 6,460 total hip
      arthroplasties done between 1986 and 2003 was performed. Wires/cables were used
      in 249 hips. It was found that one cable was broken (0.92%) compared with 11
      wires (1.72%) (P < .5373). It was found that there was no statistical difference
      in Harris hip function or pain scores between patients with wires and those with
      cables or between those with broken wires/cables and those without broken
      wires/cables. The Luque wires, which cost 29.79 US dollars each, performed
      equally to the cables, which cost 275.40 US dollars each, suggesting that wiring
      may be the preferred cerclage technique.

PMID- 17027553
TI  - Fracture of femoral component in a resurfacing total knee arthroplasty.
AB  - We present a case of an unusual complication after a resurfacing total knee
      arthroplasty. Fracture of the uncemented porous-coated femoral component occurred
      4 years after its implantation. The mechanical axis was restored and collateral
      ligament balance was achieved at the primary procedure. At revision, the femoral
      component was found fractured at the junction of the trochlea with the medial
      condyle, anteriorly to the medial peg. A thin layer of fibrous tissue was
      interposed between bone and metal under the fracture area. Metallurgical analysis
      of the fractured component revealed fatigue failure but no structural defect.
      Lack of bony support and excessive cyclic loading led to fracture of the implant.

PMID- 17027554
TI  - Fracture of a ceramic femoral head after ceramic-on-ceramic total hip
      arthroplasty.
AB  - A case of fracture of the ceramic head of a total hip arthroplasty is presented,
      which was a total cementless arthroplasty with ceramic-on-ceramic articulation.
      No history of trauma was observed. The arthroplasty was revised, and a new
      cementless arthroplasty with a polyethylene insert and a metal head was inserted.
      The result has been satisfactory.

PMID- 17027555
TI  - Cruciate-retaining stemmed total knee arthroplasty for supracondylar
      intercondylar femoral fractures in elderly patients: a report of three cases.
AB  - The treatment of supracondylar or intercondylar femoral fractures in elderly
      patients with gonarthrosis is a difficult problem. Primary total knee
      arthroplasty (TKA) can be considered as a treatment modality for these patients,
      and several authors have reported acceptable results with this option. They have
      performed TKA using custom-made, hinged, or constrained components with long stem
      for fracture reduction and stabilization. But use of hinged or constrained total
      knee arthroplasties for dealing with supracondylar and intercondylar fractures
      may be unnecessary, and an alternative is to use a cruciate-retaining stemmed
      TKA. We report 3 elderly female patients who had supracondylar or intercondylar
      femoral fractures and coexisting gonarthrosis treated by primary TKA with use of
      a cruciate-retaining augmentable femoral component with stem extension. All
      patients improved their ambulatory status and showed good knee function. We
      believe that use of a cruciate-retaining type of component is a reasonable
      alternative to the use of a more constrained prosthesis in the treatment for this
      group of patients.

PMID- 17027557
TI  - Late fatigue fracture of a modern cemented forged cobalt chrome stem for total
      hip arthroplasty: a report of 10 cases.

PMID- 17027558
TI  - Short- and long-term prognosis after acute myocardial infarction in men versus
      women.
AB  - The prevailing view is that women have a higher early mortality after acute
      myocardial infarction (AMI) than men, but several studies have shown no
      differences. Further, long-term differences have not been addressed widely. The
      present study examined gender differences in short- and long-term prognoses after
      AMI in The Netherlands. A nationwide cohort of 21,565 patients with a first
      hospitalized AMI in 1995 was identified through linkage of the National Hospital
      Discharge Register and the population register. Crude short- and long-term
      mortalities were significantly higher in women than in men (28-day hazard ratio
      [HR] 1.70, 95% confidence interval [CI] 1.58 to 1.82; 5-year HR 1.52, 95% CI 1.46
      to 1.59). After adjustment for age, the risk difference was attenuated at 28 days
      and even reversed at 5 years in favor of women (28-day HR 1.11, 95% CI 1.03 to
      1.20; 5-year HR 0.94, 95% CI 0.90 to 0.99). When differences in other covariates
      were also taken into account, the risk differences remained virtually the same.
      To account for differences in reperfusion procedures, we repeated the analyses in
      1,176 patients who underwent acute reperfusion therapy
      (angioplasty/thrombolysis). Comparable, but not statistically significant, gender
      differences were observed (28-day HR 1.06, 95% CI 0.65 to 1.74; 5-year HR 0.82,
      95% CI 0.62 to 1.08). In conclusion, our findings in an unselected cohort
      covering a complete nation indicate that the worse short- and long-term prognoses
      after an AMI in women compared with men may largely be explained by differences
      in age, whereas differences in co-morbidity, origin, infarct location, and
      reperfusion therapy seem to contribute little.

PMID- 17027559
TI  - Predictors of in-hospital mortality difference between male and female patients
      with acute myocardial infarction.
AB  - Many studies have demonstrated that, compared with men, women have increased long
      and short-term mortality after acute myocardial infarction (AMI). The reasons
      for this mortality difference remain in dispute. We analyzed baseline
      characteristics, in-hospital management, and short-term outcomes of 1,246 men and
      537 women with AMI to identify clinical variables that can predict the in
      hospital mortality difference between genders. A higher in-hospital mortality was
      found in women with AMI than in men (11.9% vs 6.9%, p <0.001). Women were
      generally older, had a higher incidence of hypertension, diabetes mellitus, and
      hyperlipidemia, and had a higher Killip class of cardiac function compared with
      men. Reperfusion therapy and beta-receptor blockers were underused in women.
      Using a multivariate logistic regression model, we identified age, history of
      hypertension and diabetes mellitus, Killip class of cardiac function, and
      administration of reperfusion therapy and beta-receptor blockers as significant
      predictors of in-hospital mortality in patients with AMI, with odds ratios of
      1.05 (95% confidence interval [CI] approximately 1.03 to 1.07), 1.65 (95% CI 1.12
      to 2.41), 1.92 (95% CI 1.27 to 2.90), 3.62 (95% CI 2.88 to 4.56), 0.39 (95% CI
      0.24 to 0.66), and 0.63 (95% CI 0.43 to 0.93), respectively. In conclusion, women
      with AMI had a higher in-hospital mortality rate than did men, probably due to
      older age, higher incidence of hypertension, diabetes mellitus, and
      hyperlipidemia, a higher Killip class of cardiac function, and less utilization
      of reperfusion therapy and beta-receptor blockers.

PMID- 17027560
TI  - Echocardiographic and angiographic correlations in patients with cardiogenic
      shock secondary to acute myocardial infarction.
AB  - In patients with cardiogenic shock (CS) complicating acute myocardial infarction,
      echocardiographic and angiographic findings are used to aid diagnosis, determine
      prognosis, and guide management. The purpose of this analysis from the Should we
      emergently revascularize Occluded Coronary arteries for Cardiogenic ShocK (SHOCK)
      trial is to identify relations between the angiographic and echocardiographic
      features of patients with CS. Such an analysis of the correlations between
      echocardiographic and angiographic findings in patients with CS may provide
      insights into the etiology and treatment of CS. In 302 randomized patients, an
      echocardiogram and an angiogram before revascularization were available in 127
      patients. Although the median ejection fraction derived by echocardiography and
      left ventricular angiography was identical (30%), the positive correlation was
      weak (R2 = 0.209, p = 0.019). Patients with a larger number of diseased vessels
      had worse mitral regurgitation (MR) by echocardiography (p = 0.005). There was a
      significant but weak association between left ventricular angiographic MR grade
      and echocardiographic MR severity (R2 = 0.162, p = 0.015), but there was no
      association between culprit vessel and degree of MR. In conclusion, worse
      coronary artery disease is associated with more severe MR. Echocardiography and
      angiography are valuable and result in similar estimated ejection fractions in a
      large cohort, but there is wide variation between the techniques in patients.

PMID- 17027561
TI  - Outcome of patients with adenosine-induced ST-segment depression but with normal
      perfusion on tomographic imaging.
AB  - Most patients with ST depression during adenosine infusion have reversible
      perfusion defects by single-photon emission computed tomographic (SPECT)
      perfusion images. Occasionally ST depression is observed in the setting of normal
      perfusion images. The outcome of such patients is controversial. We identified 65
      patients who underwent gated SPECT perfusion imaging with adenosine as the stress
      agent. These patients were selected based on the following criteria: none had
      previous myocardial infarction or coronary revascularization, all were in sinus
      rhythm, and none had left bundle branch block. The 65 patients had normal SPECT
      images but ischemic ST response (>or=1 mm ST depression). There were 52 women and
      13 men who were 66 +/- 13 years of age. History of diabetes mellitus was present
      in 16 patients (25%) and hypertension in 48 patients (74%). At a mean follow-up
      of 24 months, there were no cardiac deaths or myocardial infarctions, and there
      were 6 coronary revascularization procedures (2 coronary artery bypass graftings
      and 4 coronary stentings of 1-vessel coronary disease). One patient died of
      cancer. In conclusion, patients with no previous myocardial infarction or
      coronary revascularization who have normal SPECT images have a benign outcome
      despite the presence of ST depression (0% for death or myocardial infarction and
      4.6%/year for coronary revascularization). Balanced ischemia could not be a
      common cause for discordant perfusion and ST response.

PMID- 17027562
TI  - Genotype-phenotype association of matrix metalloproteinase-3 polymorphism and its
      synergistic effect with smoking on the occurrence of acute coronary syndrome.
AB  - Matrix metalloproteinase-3 (MMP-3) degrades the extracellular matrix and may
      contribute to the weakening of the plaque cap. To determine whether genotype
      phenotype associations differed in different categories of acute coronary
      syndrome, we enrolled 650 consecutive Taiwanese patients diagnosed with acute
      coronary syndrome. Genotypic analysis was done on DNA using polymerase chain
      reaction and direct sequencing on the 5 adenines (5A)/6 adenines (6A; -1,171 bp)
      polymorphism in the MMP-3 gene promoter region. The frequency of the 5A
      polymorphism was higher in patients with acute coronary syndrome, especially in
      those with ST-elevation myocardial infarction (p <0.01). The number of 5A allele
      polymorphisms was strongly associated with more complex coronary angiography
      (diffuse score for 5A/5A vs 5A/6A vs 6A/6A, 6.6 +/- 1.2 vs 5.3 +/- 1.3 vs 4.6 +/-
      1.1, all p values <0.05 in subgroup analysis) and higher plasma MMP-3 activity in
      this acute coronary syndrome cohort (MMP-3 level for 6A/6A vs 5A/6A vs 5A/5A,
      21.0 +/- 2.2 vs 23.3 +/- 2.1 vs 27.9 +/- 2.2 ng/ml, all p values <0.05 in
      subgroup analysis). Multiple logistic regression analysis showed that this
      polymorphism, in addition to hypertension, diabetes, and a history of smoking,
      was an independent risk factor (odds ratio 2.2, 95% confidence interval 1.1 to
      4.3, p = 0.02) for the occurrence of acute coronary syndrome. Further, carriers
      of this polymorphism who smoked had a significantly increased (20-fold) risk of
      acute coronary syndrome compared with nonsmoking noncarriers. In conclusion, the
      MMP-3 5A/6A polymorphism is significantly associated with the occurrence of acute
      coronary syndrome, MMP-3 activity, and severity of coronary atherosclerosis.
      There is a synergistic effect between smoking and this genetic risk factor for
      acute coronary syndrome.

PMID- 17027563
TI  - Comparison of 30-day outcomes in patients <75 years of age versus >or=75 years of
      age with acute myocardial infarction treated by primary coronary angioplasty.
AB  - We reviewed 1,087 consecutive patients treated by primary coronary angioplasty
      for acute myocardial infarction; 309 were >or=75 and 778 were <75 years of age.
      Compared with the younger group, the older group had higher 30-day (8.1% vs 4.0%,
      p = 0.0057) and cardiac (6.5% vs 3.6%, p = 0.038) mortality rates. Successful
      reperfusion was achieved in the 2 groups at a similarly high rate (91.6% and
      92.9%, p = 0.45). Successful compared with unsuccessful angioplasty decreased 30
      day mortality rates in the older group (6.0% vs 30.8%, p <0.0001) and in the
      younger group (3.2% vs 14.5%, p <0.0001). When reperfusion was successful, the
      cardiac mortality rate in older patients was not significantly greater than that
      in younger patients (4.6% vs 2.8%, p = 0.14). By multivariate analysis in all
      1,087 patients, overt cardiogenic shock on admission (odds ratio 44.7, 95%
      confidence interval 22.0 to 91.1, p <0.0001) and unsuccessful reperfusion (odds
      ratio 9.40, 95% confidence interval 4.11 to 21.5, p <0.0001) were found to be
      independent predictors of 30-day mortality, whereas age >or=75 years (odds ratio
      1.79, 95% confidence interval 0.91 to 3.50, p = 0.090) was not. In conclusion,
      aggressive angioplasty in older patients improves prognosis.

PMID- 17027564
TI  - Polymer-based paclitaxel-eluting stents are superior to nonpolymer-based
      paclitaxel-eluting stents in the treatment of de novo coronary lesions.
AB  - Although polymer coating of coronary stents enables sufficient loading and
      release of incorporated drugs, it has also been associated with potentially
      negative effects. This study compared the clinical, angiographic, and
      intravascular ultrasound (IVUS) outcomes of patients treated with polymer- versus
      nonpolymer-based paclitaxel-eluting stents (PESs). Sixty-five consecutive
      patients (70 de novo lesions) treated with polymer-based PESs (TAXUS, 1
      microg/mm2 of paclitaxel; Boston Scientific Corp.) and 65 consecutive patients
      (65 de novo lesions) treated with nonpolymer-based PESs (V-Flex Plus, 2.7
      microg/mm2 of paclitaxel; Cook, Inc.) were enrolled in the study. Six-month
      angiographic follow-up was performed on 54 lesions of the polymer-based PES group
      and 51 lesions of the nonpolymer-based PES group. IVUS at angiographic follow-up
      was performed in 61 of the first 70 included lesions. At 6-month IVUS follow-up,
      mean intimal hyperplasia cross-sectional area was 2.36 +/- 1.60 mm2 in the
      nonpolymer-based PES group versus 0.62 +/- 0.41 mm2 in the polymer-based PES
      group (p = 0.003). Implantation of polymer-based PESs resulted in significantly
      lower in-stent late lumen loss (0.22 +/- 0.27 vs 0.74 +/- 0.61 mm, respectively,
      p <0.001). In-stent binary restenosis rate was 5% versus 20%, respectively (p
      <0.001). Target lesion revascularization rate was 9% after implantation of
      polymer-based PES versus 18% (p = 0.128) after implantation of nonpolymer-based
      PES, and the major adverse cardiac event rate was 9% versus 23%, respectively (p
      = 0.032). In conclusion, polymer-based PESs result in superior angiographic and
      IVUS follow-up findings compared with nonpolymer-based PESs.

PMID- 17027565
TI  - Twelve-month outcomes with a paclitaxel-eluting stent transitioning from
      controlled trials to clinical practice (the WISDOM Registry).
AB  - The WISDOM Registry tracked clinical outcomes in patients receiving a slow
      release, polymer-based, paclitaxel-eluting stent during the transition from
      randomized trials to commercial use in everyday interventional cardiology
      practice. Although randomized trials of drug-eluting stents have demonstrated the
      safety and effectiveness of these devices in less complicated, de novo lesions,
      observation of long-term clinical outcomes is required to monitor safety as use
      of this revolutionary technology expands to broader patient populations. In
      total, 778 patients were enrolled at 22 sites in 9 countries where the TAXUS
      paclitaxel-eluting stent first received market approval. Patients with de novo or
      restenotic coronary lesions eligible for stenting were enrolled. Clinical follow
      up was conducted by telephone at 3, 6, 9, and 12 months after the procedure to
      capture reported stent thrombosis and major cardiac events (death, myocardial
      infarction, and reintervention on the target lesion). Clinical follow-up at 12
      months was completed for 92% of patients. The 12-month rate of physician-reported
      major cardiac events was 5.2%, with a target lesion reintervention rate of 2.0%.
      The low overall stent thrombosis rate of 0.6% included no stent thromboses >30
      days after the index procedure. Low target lesion reintervention rates were also
      observed in the high-risk subgroups: patients with diabetes (4.0%), vessels <2.5
      mm (2.5%), lesions >20 mm (3.6%), and multiple stents in a lesion (1.4%). In
      conclusion, the paclitaxel-eluting TAXUS slow-release stent exhibits long-term
      safety and efficacy in uncomplicated and higher risk patients and lesions seen in
      everyday clinical practice.

PMID- 17027566
TI  - Influence of transmurality, infarct size, and severe microvascular obstruction on
      left ventricular remodeling and function after primary coronary angioplasty.
AB  - Infarct size has been considered an established marker of left ventricular (LV)
      remodeling. We assessed the predictive value of myocardial/microvascular injury
      assessed by delayed enhanced magnetic resonance imaging (MRI) on LV remodeling
      and LV ejection fraction after primary coronary intervention (PCI) compared with
      peak troponin levels, an established index of myocardial infarct size. We
      performed MRI in 76 patients with first acute myocardial infarction 6 +/- 2 days
      after successful PCI. Necrosis was judged as transmural when delayed enhancement
      was extended to >or=75% of LV segment thickness. Severe microvascular obstruction
      was identified as areas of late hypoenhancement surrounded by delayed
      enhancement. Infarct size was expressed as an index by dividing the total
      percentage of delayed enhancement involvement by the number of LV segments. LV
      end-diastolic volume index and function were quantified by 2-dimensional
      echocardiography at 6 +/- 1 months after acute myocardial infarction. Remodeling
      was evaluated as a change in LV end-diastolic volume index at follow-up compared
      with baseline. At univariate analyses, transmural necrosis, severe microvascular
      obstruction, infarct size, and troponin level were correlated directly with
      remodeling and inversely with LV function at follow-up (p <0.001). At multiple
      regression, only transmural necrosis and troponin level remained independent
      predictors of LV remodeling and function. With respect to troponin, transmural
      necrosis improved the predictive power of LV remodeling (R2 for change = 0.19)
      and function (R2 for change = 0.16). In conclusion, in patients with acute
      myocardial infarction undergoing PCI, the amount of transmural necrosis as
      assessed by MRI is a major determinant of LV remodeling and function, with
      significant additional predictive value to infarct size and severe microvascular
      obstruction.

PMID- 17027567
TI  - Effect of plaque volume on subsequent vessel remodeling at edges of sirolimus
      eluting stents.
AB  - Serial (baseline and 9-month follow-up) intravascular ultrasound analysis was
      performed at 5-mm reference segments immediately proximal and distal to the
      sirolimus-eluting stent (SES) in 33 lesions. Proximal and distal reference
      segments were divided into 1-mm subsegments. Between postintervention and follow
      up intravascular ultrasound studies, there were significant decreases in the
      lumen and increases in plaque & media areas in the subsegment closest to the
      distal edge, with no change in external elastic membrane area. There was no
      significant change in external elastic membrane, lumen, and plaque & media areas
      within the other subsegments. At the nearest 1-mm subsegment from the proximal
      and distal edges, baseline plaque & media area was associated with subsequent
      vessel remodeling. In conclusion, a large amount of plaque at the SES edge may be
      a risk of negative remodeling at follow-up (stent edge restenosis). It supports
      the importance of "normal-to-normal" SES deployment.

PMID- 17027568
TI  - Comparison of prevalence of unrecognized myocardial infarction and of silent
      myocardial ischemia detected by a treadmill exercise sestamibi stress test in
      patients with versus without diabetes mellitus.
AB  - We investigated, in 287 patients with diabetes (71% men; mean age 63 +/- 8 years)
      and 292 age- and gender-matched patients with diabetes, the prevalence of
      unrecognized myocardial infarction (MI) and silent myocardial ischemia (SMI)
      detected by a treadmill exercise sestamibi stress test. In the patients without a
      history of MI, MI was diagnosed by treadmill exercise sestamibi stress test in 40
      of 217 patients (18%) with diabetes and 16 of 224 patients (7%) without diabetes
      (p <0.001). In patients with a history of angina, SMI was diagnosed in 35 of 98
      patients (36%) with diabetes and 30 of 101 patients (30%) without diabetes (p =
      NS). In patients without a history of angina, SMI was diagnosed in 62 of 189
      patients (33%) with diabetes and 35 of 191 patients (15%) without diabetes (p
      <0.001). In patients with 2 or 3 risk factors, SMI was diagnosed in 58 of 144
      patients (40%) with diabetes and 41 of 142 patients (29%) without diabetes (p
      <0.005). In patients with 0 or 1 risk factor, SMI was diagnosed in 39 of 143
      patients (27%) with diabetes and 24 of 150 patients (16%) without diabetes (p
      <0.02). In conclusion, patients with diabetes have a higher prevalence of
      unrecognized MI and a higher prevalence of SMI without a history of angina than
      patients without diabetes.

PMID- 17027569
TI  - A population-based, cross-sectional comparison of lipid-related indexes for
      symptoms of atherosclerotic disease.
AB  - Current lipid guidelines recommend that therapy be targeted primarily at low
      density lipoprotein (LDL) cholesterol, and that other lipid indexes may be used
      as secondary or supplementary targets. Emerging data have suggested that measures
      such as non-high-density lipoprotein (HDL) cholesterol, apolipoprotein-B, or the
      total/HDL cholesterol ratio may be more predictive of cardiovascular risk than
      LDL cholesterol. We conducted a cross-sectional analysis of data from the Third
      National Health and Nutrition Examination Survey to directly compare the
      strengths of the associations among various lipid-related indexes and clinical
      features consistent with atherosclerotic disease. From approximately 9,500 data
      sets in the overall analysis, the apolipoprotein-B/HDL cholesterol ratio emerged
      as the strongest correlate (odds ratio 1.177 per 1 mg/dl increment, 95%
      confidence interval 1.063 to 1.302, p <0.01), followed by the total or non-HDL
      cholesterol/HDL cholesterol ratio (odds ratio for each 1.070 per 1 mg/dl
      increment, 95% confidence interval 1.024 to 1.118, p <0.01), followed by the
      triglyceride/HDL cholesterol ratio (odds ratio 1.033 per 1 mg/dl increment, 95%
      confidence interval 1.011 to 1.056, p <0.01). Neither LDL cholesterol nor the
      LDL/HDL cholesterol ratio correlated significantly. Parallel analyses comparing
      tertile extremes and analyses in subgroups determined by gender, age, and body
      mass index revealed similar findings. The LDL/HDL cholesterol ratio was only
      significant for lean patients. In conclusion, these observations add to the
      published data suggesting that LDL cholesterol may not be the best target of
      lipid-lowering treatment strategies.

PMID- 17027570
TI  - Comparison of body mass index versus waist circumference with the metabolic
      changes that increase the risk of cardiovascular disease in insulin-resistant
      individuals.
AB  - This study compared the abilities of body mass index (BMI) and waist
      circumference (WC) to identify resistance to insulin-mediated glucose uptake and
      related metabolic abnormalities in 261 apparently healthy patients. Insulin
      resistance and associated metabolic abnormalities occur more commonly in the
      overweight/obese, and these changes increase the risk of cardiovascular disease
      (CVD). Determining either their BMI or WC can identify patients more likely to
      experience the adverse effects of excess adiposity on CVD risk, and the relative
      clinical utility of these measurements is not clear. Therefore, insulin-mediated
      glucose uptake was quantified in 261 apparently healthy adults by determining the
      steady-state plasma glucose concentrations during the insulin suppression test;
      the higher the concentration, the greater the defect in insulin action. The
      fasting plasma glucose, triglyceride, and total, low-density lipoprotein, and
      high-density lipoprotein cholesterol concentrations were also measured, and the
      associations between these variables and the measurements of BMI and WC were
      determined. The greater the degree of adiposity, the higher the steady-state
      plasma glucose, fasting plasma glucose, and triglyceride concentrations,
      irrespective of the index of adiposity used. However, increases in the total and
      low-density lipoprotein cholesterol and decreases in the high-density lipoprotein
      cholesterol concentrations were only seen in those with higher BMI values. In
      conclusion, because BMI performed at least as well as WC in identifying
      differences in insulin sensitivity and multiple CVD risk factors, either estimate
      can be used to identify patients at increased CVD risk.

PMID- 17027571
TI  - Relation of improvement in endothelium-dependent flow-mediated vasodilation after
      rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C
      reactive protein in nondiabetic patients with the metabolic syndrome.
AB  - The mechanisms by which thiazolidinediones exert beneficial effects on the
      endothelium are still not clear. We examined the effects of rosiglitazone on the
      plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and
      lipid profiles), markers of inflammation (high-sensitivity C-reactive protein
      [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and
      vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric
      dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between
      changes in endothelium-dependent flow-mediated dilation of the brachial artery
      and changes in these markers to elucidate their roles in mediating the vascular
      protective effects of rosiglitazone. Of 70 nondiabetic patients who met a
      modified National Cholesterol Education Program definition of the metabolic
      syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to
      receive placebo for 8 weeks. At study end, treatment with rosiglitazone had
      significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p
      <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein
      cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and
      decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (
      16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and
      diastolic blood pressures. Rosiglitazone treatment significantly improved flow
      mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001)
      of the right brachial artery. On multivariate analysis, changes in ADMA,
      endothelin-1, and CRP were independent predictors of improved endothelial
      reactivity with rosiglitazone. In conclusion, we have, for the first time,
      demonstrated the independent associations between the improvement in flow
      mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of
      treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome.
      These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as
      possible mechanisms for the improvement in endothelial function conferred by
      rosiglitazone treatment.

PMID- 17027572
TI  - Sequelae of systemic hypertension in alcohol abstainers, light drinkers, and
      heavy drinkers.
AB  - A link exists between alcohol intake and increased blood pressure (BP), with many
      studies showing increased hypertension prevalence in heavy drinkers. The harmful
      and beneficial effects of alcohol can confound the study of the long-term risks
      of alcohol-related hypertension. We therefore studied cardiovascular sequelae
      separately in heavy drinkers, light drinkers, and abstainers among 127,212
      subjects with BP and alcohol intake ascertained at 1978 to 1985 health
      examinations. Subsequent cardiovascular end points included mortality risk,
      hospitalization risk, and outpatient diagnosis of hypertension. Analyses were
      performed for all subjects and stratified by 5 alcohol-drinking categories (from
      never drinkers to >or=3 drinks/day). With <120/80 mm Hg as the referent, Cox
      proportional hazards models were used to estimate relative risks and 95%
      confidence intervals for 3 higher BP categories (120 to 129/80 to 84, 130 to
      139/85 to 89, and >or=140/90 mm Hg). The covariates were age, gender, race, body
      mass index, education, and smoking. The risk of all outcomes was progressively
      higher for increasing BP categories, with a similarly increased risk for
      abstainers, light drinkers, and heavy drinkers. The interaction tests for alcohol
      and BP were not statistically significant for the mortality and hospitalization
      outcomes. Interpretation was limited by an inability to separate subjects with
      increased BP from alcohol consumption from those with other etiologies. In
      conclusion, the data indicate that the risks of hypertension are similar
      regardless of the amount of alcohol consumption.

PMID- 17027574
TI  - Pulmonary embolism as a cause of death in adults who died with heart failure.
AB  - Although heart failure (HF) is a known risk factor for pulmonary embolism (PE),
      little is known about the frequency of death from PE in patients who die with HF.
      This investigation was undertaken to determine the frequency of PE as the cause
      of death in patients who died with HF on the basis of data from death
      certificates, as listed by the United States Census Bureau. Among adults with HF
      who died over the 19-year period of study, PE was the listed cause of death in
      20,387 of 755,807 (2.7%). Assuming that the accuracy of death certificates was
      only 26.7%, the rate of death from PE in these patients may have been as high as
      10.1%. The frequency of death from PE in patients who died with HF decreased from
      1980 to 1998. In conclusion, the estimated death rate from PE in patients who
      died with HF is 3% to 10%. A decrease over 2 decades in the proportion of deaths
      from PE in such patients is compatible with the increasing and effective use of
      antithrombotic prophylaxis.

PMID- 17027573
TI  - Effect of marital quality on eight-year survival of patients with heart failure.
AB  - Recent evidence suggests that psychosocial factors such as self-efficacy,
      psychological distress, perceived social support, and marital quality have
      prognostic significance for morbidity and mortality after heart failure.
      Previously, we reported that interview and observational measures of marital
      quality obtained from 189 patients with heart failure (139 men and 50 women) and
      their spouses predicted all-cause patient mortality during the next 4 years,
      independent of the baseline illness severity (New York Heart Association class).
      We present additional follow-up results for this sample, with Cox regression
      analyses showing that a couple-level composite measure of marital quality
      continued to predict survival during an 8-year period (p <0.001), especially when
      the patient was a woman, and did so substantially better than individual (patient
      level) risk and protective factors, such as psychological distress, hostility,
      neuroticism, self-efficacy, optimism, and breadth of perceived emotional support.
      In conclusion, relationship factors may be especially relevant in managing a
      difficult chronic condition such as heart failure, which makes stringent and
      complex demands on patients and their families.

PMID- 17027575
TI  - A novel prognostic index to determine the impact of cardiac conditions and co
      morbidities on one-year outcome in patients with heart failure.
AB  - Prognostic stratification is relevant in clinical decision making in heart
      failure (HF). Predictors identified during hospitalization or in clinical trials
      may be unrepresentative of HF in the community. The aim of this study was to
      derive and validate, in different clinical settings, a risk stratification model
      for the prediction of stable HF outcomes. The study included 807 patients, 350
      enrolled at discharge from the hospital (44%), 309 in the outpatient clinic
      (38%), and 148 in the home-care setting (18%). There were 292 patients in the
      derivation cohort and 515 in the validation cohort. A multivariate logistic
      analysis was performed to obtain the CardioVascular Medicine Heart Failure (CVM
      HF) index. One-year mortality was 20.8% in the derivation cohort and 20.7% in the
      validation cohort. The CVM-HF index included cardiac conditions and co
      morbidities and stratified the 1-year mortality risk as low (death rate 4%),
      average (32%), high (63%), and very high (96%). The area under the curve of the
      receiver-operating characteristic curve was 0.844 (95% confidence interval [CI]
      0.779 to 0.89) for the derivation cohort and 0.812 (95% CI 0.76 to 0.86) for the
      validation cohort. Model performance was equally good in the 3 different HF
      settings. In a subgroup of 409 patients, the CVM-HF index (area under the curve
      0.821, 95% CI 0.79 to 0.89) outperformed the most-used prognostic models (the
      Charlson index and the Heart Failure Risk Scoring System). In conclusion, the CVM
      HF index, a novel prognostic model that is easy to derive and applicable to
      unselected patients, may represent a valuable tool for the prognostication of
      stable HF outcomes.

PMID- 17027576
TI  - Are left ventricular diastolic function and diastolic asynchrony important
      determinants of response to cardiac resynchronization therapy?
AB  - Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and
      reverse left ventricular (LV) remodeling. It is not known, however, whether
      diastolic function will improve after CRT and diastolic asynchrony will predict
      LV reverse remodeling. Seventy-six patients (mean age 65 +/- 12 years, 74% men)
      who received CRT were studied at baseline and after 3 months. Diastolic function
      was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and
      diastolic asynchrony were assessed by the time to peak myocardial contraction
      (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental
      model. There were 42 responders (55%) with LV reverse remodeling (defined as a
      reduction of LV end-systolic volume >or=15%). Parameters of systolic function
      were significantly improved only in the responders. For diastolic function, there
      were reductions of transmitral E velocity in the 2 groups, without any change in
      atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial
      early diastolic velocity was unchanged in responders but was significantly
      worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV
      segments) correlated significantly with LV reverse remodeling (r = -0.64, p
      <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments)
      (r = -0.10, p = NS). The systolic asynchrony index was the only independent
      predictor of reverse remodeling (beta = -0.99, 95% confidence interval -1.41 to 
      0.58, p <0.001). In conclusion, CRT improves systolic function and systolic
      asynchrony but has a neutral effect on diastolic function and diastolic
      asynchrony. LV reverse remodeling response is determined by the severity of
      prepacing systolic asynchrony but not diastolic asynchrony or the diastolic
      filling pattern.

PMID- 17027577
TI  - Value of mitral valve tenting volume determined by real-time three-dimensional
      echocardiography in patients with functional mitral regurgitation.
AB  - This study sought to evaluate mitral valve tenting volume (TnV) as a clinical
      parameter using real-time 3-dimensional echocardiography in patients with
      functional mitral regurgitation (MR). In 27 patients with functional MR and 4
      controls without mitral disease, real-time 3-dimensional echocardiographic images
      were obtained to measure TnV frame by frame from presystole to end-systole. The
      maximal and minimal TnVs during systole were identified in each patient, and
      mitral annular areas and tenting heights were also measured. Using 2-dimensional
      echocardiography, tenting area (TnA) was measured from the apical long-axis,
      apical 4-chamber, and apical 2-chamber views. The regurgitant orifice area was
      measured by the proximal isovelocity surface area method. Maximal and minimal
      TnVs occurred at the time of 2 +/- 6% and 78 +/- 6% of whole systolic duration,
      respectively, and the systolic percentage change of TnV was related to that of
      tenting height but not to that of mitral annular area. TnA on the long-axis
      images was significantly larger than that on the 4- and 2-chamber images (2.5 +/-
      1.4 vs 1.7 +/- 1.3 and 1.9 +/- 1.4 cm(2), respectively, p <0.001). Regurgitant
      orifice area was significantly correlated with maximal TnV (r = 0.90), minimal
      TnV (r = 0.86), and TnA on the long-axis (r = 0.79), 4-chamber (r = 0.75), and 2
      chamber (r = 0.73) images. Among minimal TnV and 3 TnAs, minimal TnV was the only
      independent determinant of regurgitant orifice area (p <0.001). Minimal TnV
      >or=3.90 ml identified significant functional MR with a sensitivity of 86% and a
      specificity of 100%. In conclusion, TnV derived from real-time 3-dimensional
      echocardiography is a preferable novel single index for assessing mitral valve
      tethering in functional MR to TnA that is dependent on the location of 2
      dimensional planes.

PMID- 17027578
TI  - Comparison of the pattern of aortic dilation in children with the Marfan's
      syndrome versus children with a bicuspid aortic valve.
AB  - Marfan's syndrome (MS) and bicuspid aortic valves (BAVs) are associated with
      aortic dilation. Despite their histologic similarities, the 2 diseases differ
      with regard to the location of maximal aortic dilation. Echocardiographic
      analysis of aortic dimensions was performed in children with MS, children who had
      aortic dilation in the setting of nonstenotic BAVs (peak gradient <16 mm Hg), and
      healthy controls. Data on 25 patients with MS, 31 with BAVs, and 65 controls were
      analyzed. Subjects with BAVs had greater dimensions at all levels of the aortic
      root compared with normal controls. Patients with BAVs also had greater dilation
      than those with MS at the level of the annulus and the ascending aorta, with
      dilation often extending cranially beyond the region of measurement. Conversely,
      patients with MS had more focal dilation at the sinuses of Valsalva compared with
      controls and patients with BAVs. In conclusion, despite similar histologic
      abnormalities, the anatomic pattern of aortic dilation differs in children with
      MS and BAVs.

PMID- 17027579
TI  - Morphology and function of the bicuspid aortic valve with and without coarctation
      of the aorta in the young.
AB  - This study sought to determine the morphology and function of bicuspid aortic
      valves (BAVs) with and without coarctation of the aorta (CoA) in a young
      population. The transthoracic echocardiograms of 117 patients with BAVs and 62
      patients with CoA were retrospectively reviewed and compared with normal
      transthoracic echocardiographic results. In each patient, the area subtended by
      the aortic cusps and valve and the diameters of the aortic root at different
      levels were measured, and additionally in each BAV, the type of cusp fusion and
      the presence and degree of aortic stenosis and/or regurgitation were evaluated.
      The median age of patients with BAVs was 4 years (range 0 days to 34 years), and
      the median age of patients with CoA was 1.9 years (range 0 days to 16.5 years).
      BAVs with right and left coronary cusp fusion were significantly associated with
      CoA (p <0.0001) and cardiac anomalies (p <0.0001), whereas BAVs with noncoronary
      and right coronary cusp fusion were affected by valvar dysfunction (p <0.001).
      Compared with normal tricuspid aortic valves, BAVs had aortic root dilation, even
      in patients with no hemodynamic disturbance, particularly at the level of the
      ascending aorta (p <0.0001); the difference was still significant comparing BAVs
      and CoA with tricuspid aortic valves and CoA (p <0.0001). In conclusion,
      different morphologies of BAVs are associated with different cardiac
      abnormalities, valvar function, and aortic root dilation. Although detectable
      early in life, valvar dysfunction and aortic root dilation progress with age.

PMID- 17027580
TI  - Frequency of circumferential pericardial effusion by echocardiography in adults
      with foramen ovale type atrial septal defect versus ventricular septal defect.
AB  - Many published reports have described pericardial effusions in patients with
      secundum atrial septal defects. This study investigated their associated
      prevalence echocardiographically using 40 patients with isolated ventricular
      septal defects as controls in an adult patient population. Pericardial effusions
      accompanied atrial septal defects in 13 patients and ventricular septal defects
      in only 3 patients (p <0.0001). In conclusion, pericardial effusions are much
      more common (p <0.005) with uncomplicated secundum atrial septal defects than
      with uncomplicated ventricular septal defects.

PMID- 17027581
TI  - Association between the ankle-brachial index and carotid intimal medial thickness
      in the Rancho Bernardo Study.
AB  - Previous cross-sectional studies have demonstrated significant associations
      between the ankle-brachial index (ABI) and carotid intimal medial thickness
      (IMT). In a longitudinal study, 637 participants who had ABI measurements from
      1992 to 1994 were tested for carotid IMT an average of 4.8 years later. Mean age
      was 72.5 years; 60% were women. More than half (51%) were hypertensive, whereas
      28% had dyslipidemia, 56% were past or current smokers, and 6% had diabetes. The
      mean +/- SD ABI and IMT were 1.06 +/- 0.13 and 1.28 +/- 0.44 mm, respectively.
      Mean age- and gender-adjusted IMTs for the ABI groups of <or=0.90, 0.91 to 0.99,
      and 1.00 to 1.09 were significantly greater than those from 1.10 to 1.26 (1.53,
      1.49, 1.28, and 1.18 mm, respectively, p <0.05 for all). In logistic regression
      analyses, each of these ABI groups was significantly associated with increased
      odds for an IMT in the highest decile compared with an ABI of 1.10 to 1.26 (odds
      ratios 3.2, 4.3, and 2.3, respectively, p <0.05 for all). In conclusion, an ABI
      of 1.10 to 1.26 was associated with the lowest levels of cardiovascular disease
      risk factors and carotid atherosclerosis, suggesting that a new cut point for ABI
      risk stratification should be considered.

PMID- 17027582
TI  - Contrast administration reduces interobserver variability in determination of
      left ventricular ejection fraction in patients with left ventricular dysfunction
      and good baseline endocardial border delineation.
AB  - Echocardiographic contrast agents improve endocardial border delineation in
      patients with technically difficult baseline studies. With medical and device
      therapy for heart failure increasingly based on left ventricular (LV) ejection
      fraction (EF) partition values, the accurate and reproducible assessment of LV
      function is necessary. It was hypothesized that routine contrast enhancement
      would significantly reduce interobserver variability in the determination of
      LVEFs in a cohort of patients with LV dysfunction and good baseline endocardial
      delineation. All patients underwent baseline noncontrast studies followed by
      contrast-enhanced imaging using Definity. Two experienced echocardiographers,
      blinded to the clinical data, determined LVEFs using 4 different techniques:
      noncontrast estimated (NCE), noncontrast calculated (NCC), contrast estimated
      (CE), and contrast calculated (CC). Using a mixed-model procedure that allows for
      fixed and random events, the variance due to error and that due to the patient
      was obtained (interclass correlation). The proportion of variation due to the
      reader was calculated as 1--interclass correlation. Mean standardized percentage
      differences ([reader 1 EF--reader 2 EF]/mean EF) were also calculated for each
      method. The proportion of variation due to the reader was smallest in the CC
      group and largest in the NCC group (NCE = 0.21, NCC = 0.33, CE = 0.25, CC =
      0.11). The results were similar when only patients with NCE EFs >or=20% and
      <or=50% were analyzed (NCE = 0.29, NCC = 0.47, CE = 0.33, CC = 0.15). The mean
      standardized percentage difference between readers was smallest in the CC group
      for all patients and for those with NCE EFs >or=20% and <or=50%. In conclusion,
      contrast administration reduces interobserver variability in LVEF assessment,
      even in patients with good baseline endocardial border delineation, and should be
      used routinely regardless of the perceived adequacy of baseline images,
      especially if the LVEF is >or=20% and <or=50%.

PMID- 17027583
TI  - Effect of beta blockers, particularly carvedilol, on reducing the risk of events
      after acute myocardial infarction.
AB  - The morbidity and mortality rates of patients who have had acute myocardial
      infarctions (AMIs) are high. Clinical guidelines recommend that most survivors of
      AMIs without contraindications should receive long-term treatment with beta
      blockade. Beta blockers have been shown to reduce mortality and reinfarction
      after AMI, but the pharmacologic differences among beta blockers may affect their
      ability to reduce these adverse events. The beta blocker carvedilol has
      adjunctive pharmacologic properties, including alpha1-blocking, antioxidant, anti
      inflammatory, and antiarrhythmic activities that appear to underlie the outcomes
      demonstrated in experimental models and clinical trials. In conclusion, this
      review explores the experimental and clinical evidence supporting the
      preferential use of carvedilol in post-AMI patients with left ventricular
      dysfunction.

PMID- 17027584
TI  - Cardiovascular factors and cognitive impairment: a role for unsaturated fatty
      acids and Mediterranean diet?

PMID- 17027585
TI  - Is transthoracic echocardiography sufficient to identify left atrial thrombus?

PMID- 17027586
TI  - Estimation of left ventricular mass by real-time three-dimensional
      echocardiography depends on good image acquisition by two-dimensional
      echocardiography.

PMID- 17027587
TI  - Cocaine and methadone: parallel effects on the QTc interval.

PMID- 17027588
TI  - Does life-long reduction in low-density lipoprotein cholesterol reduce the risk
      of new-onset hypertension?

PMID- 17027589
TI  - A Troia horse into cardiovascular system: anabolic steroid(s).

PMID- 17027590
TI  - Clinical significance of acute neurohormonal response after levosimendan
      treatment.

PMID- 17027591
TI  - Perioperative complications and adverse events of the MONARC transobturator tape,
      compared with the tension-free vaginal tape.
AB  - OBJECTIVE: The objective of the study was to compare the incidence of
      perioperative complications of the MONARC transobturator tape with the tension
      free vaginal tape in women undergoing surgical treatment for stress urinary
      incontinence. STUDY DESIGN: A retrospective review of all patients undergoing
      either a transobturator tape or tension-free vaginal tape between January 2003
      and August 2005 was performed. The incidence of intraoperative and postoperative
      (6 weeks or less) complications was compared between groups. RESULTS: Two hundred
      five women underwent a transobturator tape and 213 women underwent a tension-free
      vaginal tape during the study period. Tension-free vaginal tape resulted in a
      significantly higher rate of bladder perforation than did transobturator tape (11
      of 213 [5%] versus 0 of 205 [0%], P < .001). Postoperatively, subjects who
      received tension-free vaginal tape were significantly more likely to require
      urethrolysis for voiding dysfunction or urinary urgency (adjusted odds ratio 3.2
      [95% confidence interval 1.2 to 10.1], P = .026) and more likely to use
      anticholinergic medications (adjusted odds ratio 2.1 [95% confidence interval
      1.02 to 4.70], P = .046) than those who received a transobturator tape.
      CONCLUSION: Transobturator tape is associated with a lower rate of bladder
      injury, a decreased incidence of postoperative anticholinergic medication use,
      and fewer urethrolyses for postoperative voiding dysfunction or urinary urgency
      than tension-free vaginal tape.

PMID- 17027596
TI  - Interlacing sleep, pain, mental disorders and organic diseases.

PMID- 17027597
TI  - The close participation of ET-1 and NO in human hepatic hemodynamics.
AB  - BACKGROUND: Nitric oxide and endothelin-1 (ET-1) are believed to closely
      participate in the hepatic circulation. However, there are no clinical studies
      evaluating the participation of these two molecules in the hepatic circulation.
      PATIENTS AND METHODS: All 27 patients had liver tumors; 6 liver tumors were
      associated with liver cirrhosis and 12 patients had chronic hepatitis. Portal
      vein and hepatic arterial blood flow was measured with an electromagnetic
      flowmeter. Blood was sampled to quantitate endothelin-1 and nitrate/nitrite
      (NO(x)) from portal veins, peripheral veins and peripheral arteries. RESULTS:
      Serum ET-1 levels tended to be higher in patients with liver cirrhosis than
      patients with chronic hepatitis or patients with normal livers. There were no
      apparent differences in NO(x) concentrations among underlying liver disease
      states. Portal blood flow and estimated total hepatic blood flow was adversely
      correlated with ET-1 in portal veins with relatively higher correlation
      coefficients whereas arterial blood flow was not correlated to ET-1. On the other
      hand, arterial plasma ET-1 concentrations were not correlated to any type of
      blood flow. NO(x) concentrations were not correlated with any type of hepatic
      blood flow. The ratio of NO(x) to ET-1 in portal veins was correlated with portal
      blood flow and estimated hepatic blood flow. This correlation coefficients were
      higher than correlation coefficients between ET-1 concentrations in portal veins,
      and portal and hepatic blood flow. CONCLUSION: ET-1 levels in portal blood are
      significantly associated with portal blood flow and total hepatic blood flow in
      humans, and ratio of NO(x) to ET-1 is better indicators than either ET-1 or NO(x)
      alone. Although this study has limitations because it was carried out in a
      clinical setting, the data may contribute to the understanding of human hepatic
      hemodynamics.

PMID- 17027598
TI  - Nurturing the voice of nursing.

PMID- 17027600
TI  - Most nurses understand that the purpose of the National Nursing Licensure
      Examination (NCLEX) is to assess a candidate's ability to provide safe, effective
      nursing care upon entry into practice in the United States and its territories.

PMID- 17027602
TI  - "Voice of the profession:" Nurse editors as leaders.

PMID- 17027603
TI  - Finding patterns of knowing in the work of Florence Nightingale.

PMID- 17027605
TI  - A framework for the study of self- and family management of chronic conditions.

PMID- 17027606
TI  - Preparing junior investigators to develop gerontological research.

PMID- 17027607
TI  - Xtreme nursing and the nursing shortage.

PMID- 17027608
TI  - Biobehavioral research at NINR and NIH.

PMID- 17027609
TI  - 1,4-Benzoquinone-based electrophoretic assay for glucose oxidase.
AB  - The communication demonstrates feasibility of an enzyme microassay for glucose
      oxidase with 1,4-benzoquinone as an acceptor of electrons. The protocol uses the
      plug-plug mode of electrophoretically mediated microanalysis, with nanolitre
      injected volumes of enzyme and reactant solutions. The reactant and product, 1,4
      benzoquinone and hydroquinone, are separated during the assay by differential
      binding to sulfated-beta-cyclodextrin used as additive to the phosphate buffer
      (pH 7) and monitored at selected wavelengths in their UV spectra. The assay
      covers glucose oxidase concentration from 0.01 to 0.1mgml(-1). Due to the strong
      UV absorbance of the both reactant and product, there is no need for use of a
      second enzyme (peroxidase) in the present assay.

PMID- 17027611
TI  - Functional genomics and its implications for molecular medicine.
AB  - Technological development in genetics and genomics provides unprecedented
      possibilities to identify the underlying molecular basic of many common diseases.
      With the availability of the human genome sequence and growing information on the
      most frequent DNA variations combined with the molecular analysis on the RNA
      expression and protein level, diseases might be characterized in the future at
      the molecular level. Describing gene function anf the specific role of DNA, RNA,
      and proteins in the disease process provides novel diagnosis tools and treatment.
      Ultimately how the unique genetic signature of an individual influences the risk
      and prognosis of disease will be the basis for individualized medicine in the
      years to come.

PMID- 17027612
TI  - Current methods for the rapid diagnosis of bioterrorism-related infectious
      agents.
AB  - Bioterrorism is the calculated use of violence against civilians to attain
      political, religious, or ideologic goals using weapons of biological warfare.
      Bioterrorism is of particular concern because these weapons can be manufactured
      with ease and do not require highly sophisticated technology. Moreover, biologic
      agents can be delivered and spread easily and can effect a large population and
      geographic area. The terrorist attacks occurring around the world necessitate
      society's continued investment in adequate defense against these unpredictable
      and irrational events.

PMID- 17027613
TI  - Human artificial chromosomes: potential applications and clinical considerations.
AB  - Human artificial chromosomes demonstrate promise as a novel class of
      nonintegrative gene therapy vectors. The authors outline current developments in
      human artificial chromosome technology and examine their potential for clinical
      application.

PMID- 17027614
TI  - Inborn errors of development: disruption of pathways critical for normal
      development.
AB  - Traditionally, congenital birth defects have been classified descriptively based
      on the observed defects. As the genes important for some birth defects have been
      identified, it is clear that several of the genes mutated in malformation
      syndromes or genes whose expression is disrupted by environmental agents or
      teratogens are part of conserved signal transduction pathways. One can consider
      malformations to be inborn errors of development whereby pathways important for
      controlling development throughout evolution have been disrupted. This article
      focuses on three highly conserved pathways and their interactions and provides a
      framework that allows pediatricians to relate the phenotype of humans who have
      developmental disorders to the functions of genes in a signal transduction
      pathway.

PMID- 17027615
TI  - Transcriptional regulation of perinatal lung maturation.
AB  - Respiration at birth depends on maturation changes in lung tissue architecture,
      cell differentiation, and gene expression. At the transcriptional level,
      maturation is controlled by the actions of a group of transcription factors
      mediating gene expression in the lung. A network of transcription factors
      regulates gene expression in the respiratory epithelium, which then influences
      cell maturation throughout the lung. Glucocorticoids (via the glucocorticoid
      receptor), acting primarily in the pulmonary mesenchyme, influence maturation in
      the respiratory epithelium. Elucidation of the intersecting pathways controlling
      perinatal lung function may provide opportunities to induce pulmonary maturation
      in preterm infants at risk for respiratory distress syndrome before birth, and
      will help identify genes and processes important for various aspects of lung
      function.

PMID- 17027616
TI  - Renal cystic disease: new insights for the clinician.
AB  - This article cannot comprehensively cover the enormous strides made in defining
      the molecular and cellular basis of renal cystic diseases over the last decade.
      Therefore, it provides a brief overview and categorization of inherited,
      developmental, and acquired renal cystic diseases, providing a relevant, up-to
      date bibliography as well as a useful list of informative Internet Web sites. Its
      major focus is the translational biology of polycystic kidney disease. It
      demonstrates how emerging molecular and cellular knowledge of the pathophysiology
      of particular diseases such as autosomal dominant polycystic kidney disease
      (ADPKD) and autosomal recessive polycystic kidney disease (ADPKD) can translate
      into innovative therapeutic insights.

PMID- 17027618
TI  - The cell biology of acute childhood respiratory disease: therapeutic
      implications.
AB  - Respiratory syncytial virus (RSV), the recently identified human metapneumovirus
      (HMPV), and the human parainfluenza viruses (HPIVs), cause most cases of
      childhood croup, bronchiolitis, and pneumonia. Influenza virus also causes a
      significant burden of disease in young children, although its significance in
      children was not fully recognized until recently. This article discusses
      pathogens that have been studied for several decades, including RSV and HPIVs,
      and also explores the newly identified viral pathogens HMPV and human coronavirus
      NL63. The escalating rate of emergence of new infectious agents, fortunately
      meeting with equally rapid advancements in molecular methods of surveillance and
      pathogen discovery, means that new organisms will soon be added to the list. A
      section on therapies for bronchiolitis addresses the final common pathways that
      can result from infection with diverse pathogens, highlighting the mechanisms
      that may be amenable to therapeutic approaches. The article concludes with a
      discussion of the overarching impact of new diagnostic strategies.

PMID- 17027617
TI  - Defects in surfactant synthesis: clinical implications.
AB  - Since the original description of deficiency of the pulmonary surfactant in
      premature newborn infants by Avery and Mead in 1959, respiratory distress
      syndrome has most commonly been attributed to developmental immaturity of
      surfactant production. Studies of different ethnic groups, gender, targeted gene
      ablation in murine lineages, and recent clinical reports of monogenic causes of
      neonatal respiratory distress syndrome have demonstrated that genetic defects
      disrupt pulmonary surfactant metabolism and cause respiratory distress syndrome,
      especially in term or near-term infants and in older infants, children, and
      adults. In contrast to developmental causes of respiratory distress, which may
      improve as infants and children mature, genetic causes result in both acute and
      chronic (and potentially irreversible) respiratory failure.

PMID- 17027619
TI  - Pulmonary hypertension in children: the twenty-first century.
AB  - Pulmonary hypertension is an elevation in pulmonary artery pressure that is
      associated with a spectrum of diseases and causes. Its clinical severity and
      presentation are widely varied. The field of study has changed immensely over the
      past several years. Significant knowledge has been gained in the pathophysiology,
      genetics, and vascular biology associated with pulmonary hypertension. These
      discoveries have contributed to medical interventions that have improved outcomes
      associated with pulmonary hypertension. This article reviews pulmonary
      hypertension in children, focusing on idiopathic pulmonary hypertension. Because
      most information is associated with children who have this form of the disease,
      formerly classified as primary pulmonary hypertension, medical therapy is
      discussed with a focus on this patient group. Additional therapeutic concepts
      relevant to other causes of pulmonary hypertension are highlighted.

PMID- 17027620
TI  - Molecular and cellular basis of congenital heart disease.
AB  - The cellular and molecular basis of congenital heart disease (CHD) is an evolving
      area of rapid discovery. This article introduced the basic mechanisms underlying
      cardiac development and CHD in order to permit a clear understanding of current
      diagnostics and therapeutics and their future development. It is clear that
      although significant advances have been made in understanding mechanisms
      controlling heart formation, the direct causes of CHD remain poorly defined.
      Future studies tha delineate the complexity of these mechanisms are required to
      provide a comprehensive understanding of the etiologies of CHD. Such
      understanding will lead to the development of novel approaches to prevention and
      therapy.

PMID- 17027621
TI  - The molecular basis of pediatric hypertension.
AB  - Blood pressure, the product of cardiac output and peripheral vascular resistance,
      follows a circadian rhythm and is altered by a host of circulating and local
      substances and by many physiologic events. The number of genes, signaling
      pathways, and systems involved in blood pressure regulation is enormous, and
      dissecting those factors that are most important in hypertension has proven
      challenging. This article discusses molecular mechanisms of hypertension in
      several conditions in which mutations in a single gene give rise to hypertension
      and then considers the contribution of these and other genes to essential
      hypertension.

PMID- 17027622
TI  - Reactive oxygen species cerebral autoregulation in health and disease.
AB  - Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that
      are produced in mammalian cells under normal and pathologic conditions. Many ROS,
      such as the superoxide anion (O2-) and hydrogen peroxide (H2O2), act as cellular
      signaling molecules within blood vessels, altering mechanisms mediating
      mechanical signal transduction and autoregulation of cerebral blood flow. This
      article focuses on the actions of ROS, such as O2.- and H2O2, and how they
      influence mechanisms responsible for the modulation of pressure-induced myogenic
      tone in the cerebral circulation and blood flow autoregulation in response to
      elevated arterial pressure. ROS may be a key target for therapeutic interventions
      in pediatric patients who have hypoxic injury or altered cerebral metabolism
      induced by trauma or infection.

PMID- 17027624
TI  - A continuous quality improvement pilot study: impact on nutritional care quality.
AB  - OBJECTIVE: All long-term care facilities are supposed to engage in quality
      improvement activities in an effort to improve care quality. The purpose of this
      pilot study was to teach long-term care staff how to conduct continuous quality
      improvement (CQI) related to nutritional care. METHODS: Research staff conducted
      CQI training in one 48-bed pilot site with designated staff members. Supervisory
      staff were taught a standardized direct observational protocol, which was
      implemented weekly by both facility and research staff, to monitor defined
      nutritional care processes under the control of direct care staff. In addition,
      direct care staff received feedback on a weekly basis about care process
      implementation. RESULTS: Following initial training and 12 weeks of CQI
      implementation, there were improvements in all 5 nutritional care processes
      related to the adequacy and quality of daily feeding assistance care provision
      according to both facility and research staff data. Weekly CQI implementation
      required approximately 1 hour of supervisory staff time and less than 15 minutes
      of direct care staff time to receive feedback. IMPLICATIONS: Both initial
      training and weekly CQI implementation were effective and required less than 2
      hours of total staff time per week. Long-term care staff in this pilot site were
      able to improve nutritional care quality using a standardized direct
      observational protocol to guide CQI activities.

PMID- 17027623
TI  - Eliciting Goals of Care in a nursing home.
AB  - OBJECTIVES: To identify enablers and barriers facing providers and staff in
      initiating Goals of Care (GOC) discussions with patients in the nursing home.
      DESIGN: Qualitative methods, one-on-one interviews. The interviews began with
      eliciting the participant's definition of GOC. The open-ended questions were
      designed to assess recent experience and satisfaction with the participant's role
      in the GOC discussion. SETTING: Nursing home. PARTICIPANTS: We interviewed 23
      nursing home staff and providers. MEASUREMENTS: Transcripts were qualitatively
      analyzed. RESULTS: Five themes emerged that were identified as barriers to
      discussing GOC: (1) Fear of legal ramifications; (2) Not enough education on how
      to have a GOC discussion; (3) Family not involved on a regular basis; (4) Time
      pressure; (5) Interdisciplinary team not involved. Five themes also emerged that
      were identified as enablers to the GOC discussion: (1) Education/experience with
      the GOC discussion; (2) Interdisciplinary team involved in the discussion; (3)
      Established trusting relationship with the patient/family/other staff; (4)
      Terminal diagnosis/hospice involvement; (5) Discussion occurs in-person.
      CONCLUSION: A major finding of these interviews is the lack of systematic
      attention to GOC in the nursing home setting. Since education and experience were
      identified as crucial to understanding GOC, more formal education and observed
      practice discussing GOC is needed for all staff. The outcomes of GOC discussions
      should be documented in the patient record and be accessible to all staff and
      communicated systematically to all staff. Addressing these barriers and
      facilitating these enablers to the GOC discussion will improve the care of
      nursing home patients.

PMID- 17027625
TI  - Nursing home involuntary relocation: clinical outcomes and perceptions of
      residents and families.
AB  - OBJECTIVES: To examine the physical and mental health characteristics of 120
      residents 3 months following their discharge from 1 transferring nursing home to
      23 facilities, to compare these characteristics to their pre-transfer status, and
      to describe resident and family perceptions of the transfer. DESIGN: Secondary
      analysis of a longitudinal, prospective quasi-experimental intervention and a
      qualitative description of resident and family views. SETTING: The setting was 23
      nursing homes in the Philadelphia metropolitan area. PARTICIPANTS: Participants
      included 120 nursing home residents and 56 family members. MEASUREMENTS: Minimum
      Data Set (MDS) and data from the Centers for Medicare and Medicaid Services (CMS)
      Nursing Home Compare Web site RESULTS: There was a statistically significant
      increase in the number of residents who fell during the post-transfer (76.9%)
      compared to the pre-transfer (51.2%) period (P = .0001): 76.3% of those with a
      history of falling prior to transfer fell during the post-transfer period while
      77.4% of those without a history of falling prior to transfer fell. Residents
      were 3.78 times more likely to fall if they required more than supervision while
      walking (95% confidence interval [CI] 1.57-9.06) and 2.65 times more likely if
      they required more than supervision while transferring (95% CI 1.09-6.44).
      Logistic regression demonstrated that the mobility was also associated with falls
      (odds ratio 1.15, 95% CI 1.05-1.26). Residents did not demonstrate any other
      significant physical or mental health changes during the 3 months following the
      involuntary transfer when compared with their pre-transfer status. Residents and
      family members clearly voiced their dismay over the process of involuntary
      relocation. CONCLUSION: Relocation is a stressful event; however, a move to a
      higher quality care environment does not result in any significant physical or
      mental health changes. The high incidence of falls post-transfer in both those
      with and without a fall history points to the need for extra fall precautions in
      newly admitted residents. In particular, frequent reorientation reminders for the
      cognitively intact and a high level of staff surveillance for all new residents
      is indicated during the first few weeks of admission.

PMID- 17027626
TI  - Which clinical indicators and resident characteristics are associated with health
      care practitioner nursing home visits or hospital transfer for urinary tract
      infections?
AB  - OBJECTIVES: (1) To determine factors associated with practitioner visitation
      and/or hospital transfer for skilled nursing facility (SNF) patients who develop
      a urinary tract infection (UTI) and (2) to determine if SNF patients with a Do
      Not Resuscitate (DNR) directive are less likely to be personally assessed and/or
      transferred to the hospital in the event of a UTI when compared to patients
      without a DNR directive. DESIGN: Retrospective cohort study using nursing home
      medical record review. PARTICIPANTS: Participants were 564 residents from 35
      nursing homes in 3 states who became acutely ill with UTI during the first 90
      days of their nursing home admission. They were identified from 2832 random
      nursing home Medicare admissions and divided into 2 groups, those with DNR
      directives (n = 334) and those without (n = 230). MEASUREMENTS: Logistic
      regression was used to determine factors associated with practitioner in-person
      assessment and/or hospitalization, and to determine differences in the likelihood
      of practitioner in-person assessment and/or hospitalization among those with DNR
      directives versus those without DNR directives. RESULTS: Only one third (29%) of
      patients with unstable vital signs were seen by a practitioner or transferred to
      a hospital. Factors associated with practitioner assessment or hospital transfer
      were elevated temperature (OR 1.7, CI 1.04-2.64), pulse more than 100 beats per
      minute (OR 1.7, CI 1.01-2.99), and delirium (OR 2.1, CI 1.267-3.44). White
      residents were less likely to be assessed by a practitioner or transferred to a
      hospital (OR 0.45, CI 0.22-0.95). DNR directives were not significantly
      associated with fewer in-person assessments (P = .067). CONCLUSION: Only one
      third of SNF patients who developed a UTI with unstable vital signs were
      personally assessed by a practitioner and/or hospitalized. Patients with delirium
      were twice as likely to be assessed or transferred to a hospital, suggesting that
      practitioners use delirium as an indicator of illness severity. However,
      practitioner visit or transfer was also associated with ethnic background. In the
      absence of good evidence regarding which nursing home residents are likely to
      benefit from hospitalization or an urgent practitioner visit, these care
      decisions will continue to be associated with factors that are unknown.

PMID- 17027627
TI  - Challenges in transitional care between nursing homes and emergency departments.
AB  - OBJECTIVE: To obtain opinions of knowledgeable professionals involved in the
      emergency care of nursing home (NH) residents. DESIGN: Structured focus group
      interviews. PARTICIPANTS: Five provider categories, including NH staff, NH
      physicians and nurse practitioners, emergency medical services (EMS) providers,
      emergency department (ED) nurses, and ED physicians. SETTING: Two NHs, 2 EDs, and
      a county-wide EMS system. ANALYSIS: Audiotaped discussions were transcribed and
      analyzed independently by 2 authors. RESULTS: Themes included barriers to
      providing high-quality care, data needed when residents are transported in both
      directions between EDs and NHs, and possible solutions to improve care.
      Communication problems were the most frequently cited barrier to providing care.
      Residents are often transported in both directions without any written
      documentation; however, even when communication does occur, it is often not in a
      mode that is useable by the receiving provider. ED personnel need a small amount
      of organized, written information. When residents are released from the ED, NH
      personnel need a verbal report from ED nurses as well as written documentation.
      All groups were optimistic that communication can be improved. Ideas included use
      of (1) fax machines or audiotape cassette recorders to exchange information, (2)
      an emergency form in residents' charts that contains predocumented information
      with an area to write in the reason for transfer, and (3) brief NH-to-ED and ED
      to-NH transfer forms that are accepted and used by local NHs and EDs. CONCLUSION:
      The transitional care of NH residents is laden with problems but has solutions
      that deserve additional development and investigation.

PMID- 17027628
TI  - Barriers to the implementation of palliative care in the nursing home.

PMID- 17027629
TI  - An unintended consequence: fatal amiodarone pulmonary toxicity in an older woman.
AB  - Amiodarone pulmonary toxicity represents the most serious adverse reaction from
      amiodarone use. It remains underdiagnosed and can have a variable presentation.
      The elderly population is at increased risk for amiodarone pulmonary toxicity.
      Thus, clinicians should prescribe the lowest dosage possible in the elderly and
      have a low threshold to discontinue the amiodarone for anyone with unexplained
      fatigue, dyspnea, cough, or weight loss. We present the case of an 89-year-old
      female who presented with a several month history of fatigue and recent
      development of dyspnea on exertion and a dry cough. She had been taking
      amiodarone for 1 year secondary to atrial fibrillation. Chest x-ray and chest CT
      revealed multilobar airway opacities. An infectious work-up was negative and a
      transbronchial biopsy revealed prominent intra-alveolar foamy macrophages,
      consistent with amiodarone pulmonary toxicity. Despite the prompt discontinuation
      of her amiodarone and a trial of intravenous steroids, the patient succumbed to
      respiratory failure. The risk factors, clinical presentation, diagnosis,
      treatment, and prevention of amiodarone pulmonary toxicity are discussed.

PMID- 17027630
TI  - The application of evidence-based principles of care in older persons (issue 4):
      pain management.

PMID- 17027631
TI  - The new F-tag 314: prevention and management of pressure ulcers.

PMID- 17027632
TI  - Defining and measuring quality outcomes in long-term care.
AB  - The US health care industry increasingly agrees that sharing information about
      quality of care is necessary to stimulate providers' efforts to improve the
      quality of health care. The availability of mandated, uniform clinical data in
      all nursing homes and home health agencies has facilitated the rapid adoption of
      public reporting of comparative quality data. This paper examines the conceptual
      and technical challenges underlying the application of information about long
      term care provider quality to judge and compare the quality of care provided by
      nursing homes and home health agencies. In general, the impetus to apply the
      emerging set of quality "tools" based on mandated clinical assessments may have
      outstripped the evidence for their valid application in selecting top providers
      or for rewarding their superior performance.

PMID- 17027633
TI  - A point mutation (R192H) in the C-terminus of human cardiac troponin I causes
      diastolic dysfunction in transgenic mice.
AB  - Cardiac troponin I (cTnI) mutations have been linked to the development of
      restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in
      human cTnI C-terminus, arginine192-->histidine (R192H) by cardiac specific
      expression of the mutated protein (cTnI(193His) in mouse sequence) in transgenic
      mice. Heart tissue sections revealed neither significant hypertrophy nor
      ventricular dilation in cTnI(193His) mice. The main functional alteration
      detected in cTnI(193His) mice by ultrasound cardiac imaging examinations was
      impaired cardiac relaxation manifested by a decreased left ventricular end
      diastolic dimension (LVEDD) and an increased end diastolic dimension in both
      atria. The cardiac ejection fraction (EF) was not significant changed in 6- to 8
      week-old cTnI(193His) mice, however, the EF was significantly decreased in
      cTnI(193His) mice at age of 11 months. These data indicate that individual
      genetic conditions and environmental factors participate together in the
      development of the cTnI mutation based-cardiac muscle disorders. This mouse model
      provides us with a tool to further investigate the pathophysiology and the
      development of RCM.

PMID- 17027634
TI  - Conformational and functional studies of gomesin analogues by CD, EPR and
      fluorescence spectroscopies.
AB  - The aim of this work was to examine the bioactivity and the conformational
      behavior of some gomesin (Gm) analogues in different environments that mimic the
      biological membrane/water interface. Thus, manual peptide synthesis was performed
      by the solid-phase method, antimicrobial activity was evaluated by a liquid
      growth inhibition assay, and conformational studies were performed making use of
      several spectroscopic techniques: CD, fluorescence and EPR. [TOAC(1)]-Gm;
      [TOAC(1), Ser(2,6,11,15)]-Gm; [Trp(7)]-Gm; [Ser(2,6,11,15), Trp(7)]-Gm; [Trp(9)]
      Gm; and [Ser(2,6,11,15), Trp(9)]-Gm were synthesized and tested. The results
      indicated that incorporation of TOAC or Trp caused no significant reduction of
      antimicrobial activity; the cyclic analogues presented a beta-hairpin
      conformation similar to that of Gm. All analogues interacted with negatively
      charged SDS both above and below the detergent's critical micellar concentration
      (cmc). In contrast, while Gm and [TOAC(1)]-Gm required higher LPC concentrations
      to bind to micelles of this zwitterionic detergent, the cyclic Trp derivatives
      and the linear derivatives did not seem to interact with this membrane-mimetic
      system. These data corroborate previous results that suggest that electrostatic
      interactions with the lipid bilayer of microorganisms play an important role in
      the mechanism of action of gomesin. Moreover, the results show that hydrophobic
      interactions also contribute to membrane binding of this antimicrobial peptide.

PMID- 17027636
TI  - Identification of conserved lentiviral sequences as landmarks of genomic
      flexibility.
AB  - Considering that recombinations produce quasispecies in lentivirus spreading, we
      identified and localized highly conserved sequences that may play an important
      role in viral ontology. Comparison of entire genomes, including 237 human, simian
      and non-primate mammal lentiviruses and 103 negative control viruses, led to
      identify 28 Conserved Lentiviral Sequences (CLSs). They were located mainly in
      the structural genes forming hot spots particularly in the gag and pol genes and
      to a lesser extent in LTRs and regulatory genes. The CLS pattern was the same
      throughout the different HIV-1 subtypes, except for some HIV-1-O strains. Only
      CLS 3 and 4 were detected in both negative control HTLV-1 oncornaviruses and D
      particle-forming simian viruses, which are not immunodeficiency inducers and
      display a genetic stability. CLSs divided the virus genomes into domains allowing
      us to distinguish sequence families leading to the notion of 'species self'
      besides that of 'lentiviral self'. Most of acutely localized CLSs in HIV-1s (82%)
      corresponded to wide recombination segments being currently reported.

PMID- 17027637
TI  - Midgut glycosidases activities in monophagous larvae of Apollo butterfly,
      Parnassius apollo ssp. frankenbergeri.
AB  - Parnassius apollo (Lepidoptera, Papilionidae) declines on numerous localities all
      over Europe. Its local subspecies frankenbergeri, inhabiting the Pieniny Mts
      (southern Poland) and successfully recovered from extinction, is monophagous in
      larval stage. In natural conditions, it completes development on the orpine Sedum
      telephium ssp. maximum. Since proper quality and quantity of necessary
      nutritional compounds of the food plant ensure developmental success, the
      digestive processes in the insect midgut should reflect adaptation to a specific
      food source. The paper presents, for the first time, the activity of detected
      glycolytic enzymes in midgut tissue and liquid gut contents of the L4 and L5
      instars of P. apollo larvae. alpha-Amylase plays the main role in utilization of
      carbohydrates, contrary to cellulase activity. Saccharase seems to be the main
      disaccharidase, and high activity of beta-glycosidase enables hydrolysis of the
      plant glycosides. Trehalase activity was unexpectedly low and comparable to those
      of cellobiase and lactase. alpha-Amylolytic and other glycolytic activities
      indicate that larvae utilize starch and other carbohydrate compounds as energy
      sources. Possible use of some plant allelochemicals as energy sources by Apollo
      larvae is discussed.

PMID- 17027638
TI  - [Impact of green tea on oxidative stress induced by ammonium metavanadate
      exposure in male rats].
AB  - Transitional metals, as vanadium, are known to exert noxious effects by
      generating oxidative stress. Addition of antioxidants in the diet could decrease
      the cytotoxic effect related to the oxidative stress. The present study, carried
      out in Wistar rats, is a contribution to the evaluation of protective effects of
      green tea Camellia sinensis, which is known to be rich in antioxidant compounds
      (polyphenols...). Rats were divided into four groups: (C) was control, (V) was
      given ammonium metavanadate (AMV), (TH) was given herbal tea as drink (66 g/l)
      and TH + V was given tea and metavanadate. Group (TH) was given herbal tea one
      month before vanadium treatment. Metavanadate was daily i.p. injected (5 mg
      NH4VO3/kg body weight) for 10 days. (C) and (TH) groups received i.p. injections
      of 0.9% NaCl during the same period. Changes in lipid peroxidation levels (TBARS)
      in kidney, liver and testes, serum concentrations of vitamins E and A and
      superoxidismutase (SOD) and catalase (CAT) activities in blood cells were
      determined. One month pre-treatment with green tea, followed by 10 days of
      treatment (TH) did not change TBARS in liver and testes as compared to controls,
      but induced a clear decrease of TBARS in kidneys. Intraperitoneal administration
      of AMV to rats (V) induced a time-dependant increase of TBARS in kidney, liver
      and testes that was lowered in rats (V + TH) drinking tea. Vitamin E
      concentrations were found to be drastically decreased from day 1 to 10 in rats
      (V). Vitamin A concentration was decreased at day 10 only. Drinking tea lowered
      AMV inhibitory effects in rats (V + TH), and conversely an increase of vitamins A
      and E concentrations were found at day 10. SOD and catalase activities were found
      increased in the blood cells from day 1 to day 5 and conversely decreased at day
      10. In contrast, associated to green tea, AMV did not affect SOD and catalase
      activities compared to controls.

PMID- 17027639
TI  - Spatio-temporal dynamics of the nematode Anguillicola crassus in Northeast
      Tunisian lagoons.
AB  - Anguillicola crassus, parasite nematode of the European eel Anguilla anguilla,
      was recorded for the first time in Tunisia (1999) in the Ichkeul lagoon. Its
      distribution has since spread toward Bizerte and Ghar El Melh lagoons. The
      monthly epidemiological survey reveals that A. crassus exists throughout the year
      in the Ichkeul lagoon. In this lagoon, its prevalence is low in winter (12% in
      December), with a marked increases in the spring reaching a maximum in March
      (35%), before it starts to decrease in summer with a minimum in July (4.35%),
      which in turn is followed by a pronounced new rise in autumn (30% in November).
      However, mean intensity values do not show such a marked variation. The majority
      of the values are between 1 and 1.5 parasites per host. In the Bizerte and Ghar
      El Melh lagoons, the presence of this nematode is limited only to one to three
      months. Investigations in the Tunis lagoon did not reveal until now the presence
      of A. crassus. It has been observed that the length of the eel influences the
      prevalence values: A. crassus becomes less common if the length of the eel
      increases. Comparatively with the global epidemiological values of A. crassus
      signalled subsequently (1999) in the Ichkeul lagoon, we note that the present
      values record a clean increase.

PMID- 17027640
TI  - [Implication of glutamate, isocitrate and malate deshydrogenases in nitrogen
      assimilation in the cadmium-stressed tomato].
AB  - Tomato seedlings grown on nitric medium and treated with various cadmium
      concentrations (0 to 50 microM) were used. Results obtained show that cadmium
      remains predominantly located in the roots, which then seem to play the role of
      trap-organs. Increasing cadmium concentration in the medium leads particularly to
      a decrease in NO3- accumulation, together with a decrease in the activity of
      glutamine synthetase and in the quantity of plastidic isoform ARNm (GS2), and, on
      the contrary, to an increase of the cytosolic isoform ARNm (GS1). On the other
      hand, stimulations were observed for NADH-dependent glutamate synthase, NADH
      dependent glutamate dehydrogenase, ARNm quantity of this enzyme, ammonium
      accumulation, and protease activity. In parallel, stimulations were observed for
      NAD+ and NADP+-dependent malate dehydrogenase and NADP+-dependent isocitrate
      dehydrogenase. These results were discussed in relation to the hypothesis
      attributing to the dehydrogenase enzymes (GDH, MDH, ICDH) an important role in
      the plant defence processes against cadmium-induced stresses.

PMID- 17027641
TI  - Dynamical and statistical models of vertebrate population dynamics.
AB  - Population dynamics methodology now powerfully combines discrete time models
      (with constant parameters, density dependence, random environment, and/or
      demographic stochasticity) and capture-recapture models for estimating
      demographic parameters. Vertebrate population dynamics has strongly benefited
      from this progress: survival estimates have been revised upwards, trade-offs
      between life history traits have been demonstrated, analyses of population
      viability and management are more and more realistic. Promising developments
      concern random effects, multistate and integrated models. Some biological
      questions (density dependence, links between individual and population levels,
      and diversification of life histories) can now be efficiently attacked.

PMID- 17027642
TI  - Relevance of various formulations of phytoplankton chlorophyll a:carbon ratio in
      a 3D marine ecosystem model.
AB  - Numerous experimental studies showed that the phytoplankton Chla-to-Carbon ratio
      (Chla:C) is highly variable, whereas most of the marine ecosystem models use a
      constant ratio. In this work, we tested three different formulations for
      computing the modelled Chla in a 3D coupled hydrodynamical-biogeochemical model
      of the Southwest lagoon of New Caledonia. The first formulation considers a
      constant Chla:C ratio. In the second one, Chla is a diagnostic variable related
      to the variable phytoplankton nitrogen-to-carbon ratio. In the last formulation,
      Chla is a state variable of the model, which is dynamically simulated. Results
      showed important differences between the formulations, the first leading to
      overestimate the Chla concentration in low nutrients conditions. Thus, this study
      strengthens the importance of the Chla modelling in a coupled model in order to
      better estimate a crucial variable for validation of ecosystem models.

PMID- 17027643
TI  - New proposals for naming lower-ranked taxa within the frame of the International
      Code of Zoological Nomenclature.
AB  - The recent multiplication of cladistic hypotheses for many zoological groups
      poses a challenge to zoological nomenclature following the International Code of
      Zoological Nomenclature: in order to account for these hypotheses, we will need
      many more ranks than currently allowed in this system, especially in lower
      taxonomy (around the ranks genus and species). The current Code allows the use of
      as many ranks as necessary in the family-series of nomina (except above
      superfamily), but forbids the use of more than a few ranks in the genus and
      species-series. It is here argued that this limitation has no theoretical
      background, does not respect the freedom of taxonomic thoughts or actions, and is
      harmful to zoological taxonomy in two respects at least: (1) it does not allow to
      express in detail hypothesized cladistic relationships among taxa at lower
      taxonomic levels (genus and species); (2) it does not allow to point
      taxonomically to low-level differentiation between populations of the same
      species, although this would be useful in some cases for conservation biology
      purposes. It is here proposed to modify the rules of the Code in order to allow
      use by taxonomists of an indeterminate number of ranks in all nominal-series.
      Such an 'expanded nomenclatural system' would be highly flexible and likely to be
      easily adapted to any new finding or hypothesis regarding cladistic relationships
      between taxa, at genus and species level and below. This system could be useful
      for phylogeographic analysis and in conservation biology. In zoological
      nomenclature, whereas robustness of nomina is necessary, the same does not hold
      for nomenclatural ranks, as the latter are arbitrary and carry no special
      biological, evolutionary or other information, except concerning the mutual
      relationships between taxa in the taxonomic hierarchy. Compared to the Phylocode
      project, the new system is equally unambiguous within the frame of a given
      taxonomic frame, but it provides more explicit and informative nomina for non
      specialist users, and is more economic in terms of number of nomina needed to
      account for a given hierarchy. These ideas are exemplified by a comparative study
      of three possible nomenclatures for the taxonomy recently proposed by Hillis and
      Wilcox (2005) for American frogs traditionally referred to the genus Rana.

PMID- 17027644
TI  - [Laurentaeglyphea, a new genus for the second recent species of Glypheid recently
      discovered. (Crustacea Decapoda Glypheidae)].
AB  - In 1975, a recent member of a large group of Crustacea Decapoda was described as
      Neoglyphea inopinata Forest & de Saint Laurent, until now only known as fossils
      and presumed extinct since the Eocene. The only known specimen had been collected
      in the Philippine waters, in 1908, at a depth of 200 m. During the next years,
      three oceanographical expeditions gave more adult specimens, allowing complete
      study of the species. From its morphology, it appeared that the status attributed
      to glypheids in the past in the classification of Decapoda Crustacea was quite
      erroneous. This group, until then considered as related to Palinurids (rock
      lobsters) was in fact much closer to Astacids (lobster, crayfish, etc.). In 1982,
      N. inopinata was recorded from the other side of Equator, from the Timor Sea. In
      October 2005, a second living species of glypheid was discovered southwest of New
      Caledonia. It was named Neoglyphea neocaledonica B. Richer de Forges, 2006.
      However, important and significant differences set apart the two species,
      especially the ornamentation of the cephalothorax, the conformation of the
      cephalic part and the proportions of epistom and thoracic appendages, being much
      more robust. It seems justified to establish, for the more recently described
      species, a new genus, Laurentaeglyphea, much closer to fossil forms.

PMID- 17027645
TI  - Low dose cadmium poisoning results in sustained ERK phosphorylation and caspase
      activation.
AB  - Cadmium poisoning has been known to result in a wide variety of cellular
      responses, including oxidative stress and kinase activation. It has been reported
      that ERK is activated following acute cadmium exposure, and this response is
      commonly seen as a classical ERK survival mechanism. Here, we analyzed different
      cell types for their responses to low concentrations of cadmium poisoning. We
      found that there is an association between cell susceptibility to cadmium
      toxicity and ERK activation. This activation is atypical, since it consists of a
      sustained ERK phosphorylation, that lasts up to 6 days post stimulation. This
      activation is associated with the appearance of cleaved caspases 8 and 3,
      processed PARP, and irreversible damage. Pharmacological inhibition of ERK
      phosphorylation results in the ability of cells to resist cadmium poisoning. Our
      data indicate that low cadmium concentrations result in an unconventional ERK
      sustained phosphorylation, which in turn leads to death signaling.

PMID- 17027646
TI  - Binding of glutamate receptor delta2 to its scaffold protein, Delphilin, is
      regulated by PKA.
AB  - The glutamate receptor delta2 (GluRdelta2) is selectively expressed in cerebellar
      Purkinje cells and plays an important role in motor learning, motor coordination,
      and long-term depression. Delphilin is identified as a GluRdelta2-interacting
      protein, selectively expressed in Purkinje cell-parallel fiber synapses, and
      specifically interacts with the GluRdelta2 C-terminus via its PDZ domain. Here,
      surface plasmon resonance analyses showed that Delphilin PDZ bound to GluRdelta2
      C-terminal peptide (DPDRGTSI), but not to its phosphopeptides (DPDRGphosphoTSI
      and DPDRGTphosphoSI). We showed the incorporation of phosphate into threonine at 
      2 (-2T) and serine at -1 (-1S) of GluRdelta2 C-terminus by cAMP-dependent protein
      kinase (PKA) in vitro. In the experiments using heterologous expression system,
      Delphilin coimmunoprecipitated with GluRdelta2 was dramatically decreased under
      the condition with forskolin and isobutylmethylxanthine, which led to cAMP
      dependent phosphorylation by PKA. Thus, phosphorylation of -2T and/or -1S of
      GluRdelta2 C-terminus by PKA may regulate the binding of GluRdelta2 to its
      scaffolding protein, Delphilin.

PMID- 17027647
TI  - ESE-3 transcription factor is involved in the expression of death receptor (DR)-5
      through putative Ets sites.
AB  - The death receptor 5 (DR-5), a receptor for tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL), is critical for TRAIL-mediated apoptosis in
      various tumor cells. The ESE-3, a member of Ets transcription factors, regulates
      the expression of a variety of cellular genes by binding to purine-rich GGAA/T
      core sequence in cooperation with other transcription factors and co-factors. In
      this study, we demonstrate for the first time that ESE-3 regulates DR-5
      expression through Ets binding sequences on the DR-5 promoter. Using a
      combination of the electrophoretic mobility shift assay and the luciferase
      reporter assay, we identified putative Ets sites responsible for ESE-3
      transcriptional activity on the DR-5 promoter. In addition, we show the possible
      involvement of co-factors CBP and p300 in ESE-3-mediated DR-5 up-regulation.

PMID- 17027648
TI  - The interaction of mammalian Class C Vps with nSec-1/Munc18-a and syntaxin 1A
      regulates pre-synaptic release.
AB  - Membrane docking and fusion in neurons is a highly regulated process requiring
      the participation of a large number of SNAREs (soluble N-ethylmaleimide sensitive
      factor attachment protein receptors) and SNARE-interacting proteins. We found
      that mammalian Class C Vps protein complex associated specifically with nSec
      1/Munc18-a, and syntaxin 1A both in vivo and in vitro. In contrast, VAMP2 and
      SNAP-25, other neuronal core complex proteins, did not interact. When co
      transfected with the human growth hormone (hGH) reporter gene, mammalian Class C
      Vps proteins enhanced Ca2+-dependent exocytosis, which was abolished by the Ca2+
      channel blocker nifedipine. In hippocampal primary cultures, the lentivirus
      mediated overexpression of hVps18 increased asynchronous spontaneous synaptic
      release without changing mEPSCs. These results indicate that mammalian Class C
      Vps proteins are involved in the regulation of membrane docking and fusion
      through an interaction with neuronal specific SNARE molecules, nSec-1/Munc18-a
      and syntaxin 1A.

PMID- 17027649
TI  - ErbB-4 and TNF-alpha converting enzyme localization to membrane microdomains.
AB  - Sequential proteolytic processing of ErbB-4 occurs in response to ligand
      addition. Here, we assess the localization of cleavable and non-cleavable ErbB-4
      isoforms to membrane microdomains using three methodologies: (1) Triton X-100
      insolubility, (2) Brij98-insolubility, and (3) detergent-free density gradient
      centrifugation. Whereas ErbB-4 translocated to a Triton X-100-insoluble fraction
      upon treatment of T47D cells with heregulin, it constitutively associated with a
      Brij98-insoluble fraction and a lipid raft fraction isolated using detergent-free
      methodology. Comparison of cleavable and non-cleavable isoforms of ErbB-4
      revealed that both ErbB-4 isoforms are constitutively localized to either a
      Triton X-100-soluble or Brij98-insoluble fraction. In contrast, addition of
      heregulin resulted in translocation of the cleavable isoform to a detergent-free
      lipid raft. Tumor necrosis factor-alpha converting enzyme (TACE), the ectodomain
      secretase for ErbB-4, was present predominantly in its mature active form in most
      microdomains analyzed. These data suggest the assembly of ErbB-4 ectodomain
      cleavage apparatus in a membrane microdomain.

PMID- 17027650
TI  - Thrombin induces rapid PAR1-mediated non-classical FGF1 release.
AB  - Thrombin induces cell proliferation and migration during vascular injury. We
      report that thrombin rapidly stimulated expression and release of the pro
      angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to
      induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts,
      indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1
      expression and release were induced by TRAP, a specific oligopeptide agonist of
      PAR1. These results identify a novel aspect of the crosstalk between FGF and
      thrombin signaling pathways which both play important roles in tissue repair and
      angiogenesis.

PMID- 17027651
TI  - Surface functionalization of inorganic nano-crystals with fibronectin and E
      cadherin chimera synergistically accelerates trans-gene delivery into embryonic
      stem cells.
AB  - Stem cells holding great promises in regenerative medicine have the potential to
      be differentiated to a specific cell type through genetic manipulation. However,
      conventional ways of gene transfer to such progenitor cells suffer from a number
      of disadvantages particularly involving safety and efficacy issues. Here, we
      report on the development of a bio-functionalized inorganic nano-carrier of DNA
      by embedding fibronectin and E-cadherin chimera on the carrier, leading to its
      high affinity interactions with embryonic stem cell surface and accelerated trans
      gene delivery for subsequent expression. While only apatite nano-particles were
      very inefficient in transfecting embryonic stem cells, fibronectin-anchored
      particles and to a more significant extent, fibronectin and E-cadherin-Fc
      associated particles dramatically enhanced trans-gene delivery with a value
      notably higher than that of commercially available lipofection system. The
      involvement of both cell surface integrin and E-cadherin in mediating
      intracellular localization of the hybrid carrier was verified by blocking
      integrin binding site with excess free fibronectin and up-regulating both
      integrin and E-cadherin through PKC activation. Thus, the new establishment of a
      bio-functional hybrid gene-carrier would promote and facilitate development of
      stem cell-based therapy in regenerative medicine.

PMID- 17027652
TI  - A high affinity human antibody antagonist of P-selectin mediated rolling.
AB  - We have characterized the IgG form of a previously isolated and engineered single
      chain Fv (scFv), named RR2r3s4-1, that binds to human PSGL-1. This fully human
      IgG was determined to have a Kd of 1.8+/-0.7 nM by fluorescence quenching
      titration. It better inhibits P-selectin-PSGL-1 interactions than a commercially
      available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling
      than KPL1. Thus, RR2r3s4-1 is the most effective antibody at inhibiting P
      selectin-PSGL-1 interactions known. Specificity analysis reveals that RR2r3s4-1
      does not cross react with murine PSGL-1 and thus requires more than tyrosine
      sulfate for binding to human PSGL-1. This evidence demonstrates the therapeutic
      potential of this antibody as a potent anti-inflammatory therapeutic.

PMID- 17027653
TI  - Treatment of diffuse large B-cell lymphomas.

PMID- 17027654
TI  - Diffuse aggressive histologies of non-hodgkin lymphoma: treatment and biology of
      limited disease.
AB  - A quarter century has passed since the paradigm for treating aggressive
      histologies of non-Hodgkin lymphoma (NHL) presenting with limited extent of
      disease (LD) changed from using aggressive surgical staging techniques followed
      by primary radiotherapy (RT) to clinical staging followed by initial treatment
      with doxorubicin-containing chemotherapy (CT). This paradigm shift occurred for
      two reasons. First, unlike the predictable contiguous spread of Hodgkin lymphoma
      from one lymph node region to the next, the NHLs are largely systemic diseases
      characterized by early hematogenous spread. Second, the discovery of a potential
      curative combination of drugs, including cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP), for use in advanced disease could eradicate
      micro-metastatic disease in patients with LD. The focus of current investigation
      on controlling the systemic nature of the disease has not changed. In this
      regard, new effective systemic therapies using combination chemotherapy plus
      monoclonal antibodies have resulted in improved outcome for patients with
      advanced disease and those treatment strategies are now under investigation in
      patients with LD.

PMID- 17027655
TI  - Standard treatment of advanced-stage diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma and is not
      localized in 70% of the cases. Even if the clinical picture, the morphologic
      aspect, and the prognostic parameters are different from one patient to another,
      the standard treatment is the same for all patients. Currently, treatment
      decision is based on the International Prognostic Index (IPI) and age of the
      patient. Outcome has been completely modified with the introduction of rituximab
      in combination with chemotherapy. A review of standard treatment and remaining
      questions is presented.

PMID- 17027656
TI  - Dose-intensified treatment of advanced-stage diffuse large B-cell lymphomas.
AB  - The introduction of the CHOP (cyclophosphamide, doxorubicin, vincristine, and
      prednisone) regimen 30 years ago was the great breakthrough in the treatment of
      advanced-stage aggressive lymphomas. About 50% of all patients treated with CHOP
      achieved complete remission, and about one third experienced long-term disease
      free survival and cure. Attempts to improve results by modifications of CHOP
      using escalated doses, additional drugs, or the alternative use of putatively non
      cross-resistant chemotherapy regimens were not confirmed in randomized trials.
      With the availability of granulocyte colony-stimulating factor (G-CSF) and the
      tool of autologous stem cell support in the 1990s, dose escalation, dose
      densification (by interval reduction), or combinations thereof were pursued to
      increase dose intensity. While dose-escalation strategies, including high-dose
      approaches necessitating stem cell support, have not been demonstrated
      unequivocally yet to be superior to a baseline CHOP-21, dose-dense (biweekly)
      modifications improved the outcome of young and elderly patients with aggressive
      lymphomas compared to baseline CHOP-21. The challenges in the era of the
      monoclonal antibody rituximab are the identification of the ideal chemotherapy
      partner for rituximab both with respect to potential synergistic effects and to
      the lack of interference with its effector mechanisms. Finally, the issue of
      intensifying rituximab within such approaches must be addressed by appropriately
      designed randomized trials.

PMID- 17027657
TI  - Drug resistance in diffuse large B-cell lymphoma.
AB  - Despite significant advances in the treatment of diffuse large B-cell lymphoma
      (DLBCL), drug resistance remains a major cause of treatment failure. Early
      strategies to improve outcome were mostly empiric or relied on classical
      mechanisms of drug resistance and were largely unsuccessful. More recent
      approaches have been aided by an understanding of the molecular pharmacology of
      drug action and tumor biology. Microarray profiling in particular has provided
      important insights into the complex biology of DLBCL and has led to a molecular
      taxonomy based on cell of origin and pathways of lymphomagenesis. It is now
      recognized that drug resistance is a complex and dynamic process related to cell
      cycle and apoptotic pathways, cellular differentiation, and the microenvironment.
      Drugs that target potential pathways of drug resistance, such as nuclear factor
      kappaB (NFkappaB), cyclin-dependent kinases (CDKs), and BCL-2 have entered
      clinical trials. However, the complexity of drug resistance requires that future
      clinical trials incorporate molecular translational endpoints to help identify
      the biologic basis of treatment failure.

PMID- 17027658
TI  - Role of hematopoietic stem cell transplantation for advanced-stage diffuse large
      cell B-cell lymphoma-B.
AB  - The prognosis of patients with relapsed or refractory diffuse large cell B-cell
      lymphoma-B (DLCL-B) is poor with conventional salvage chemotherapy; therefore,
      high-dose therapy (HDT) combined with autologous stem cell transplant (ASCT) has
      become the treatment of choice for these patients. The outcomes of transplant are
      better in patients with chemosensitive relapse: those with a longer duration of
      first remission (>12 month) and those with an age-adjusted low-risk International
      Prognostic Index (IPI) at relapse. Several high-dose regimens with or without
      total body irradiation (TBI) have been used with similar outcomes. Relapse
      remains the most common cause of treatment failure, and thus the use of
      radioimmunotherapy (RIT) in the high-dose regimens and incorporation of rituximab
      in the transplant setting have been explored. Several studies have shown that RIT
      both at conventional dose and at high dose can be given in combination with high
      dose chemotherapy regimens without additional toxicity or delay in hematopoietic
      recovery after ASCT. Additional studies using RIT in combination with high-dose
      chemotherapy and ASCT are ongoing, and preliminary results suggest that these
      approaches may be superior to conventional high-dose regimens. Since rituximab is
      an effective therapy for B-cell non-Hodgkin's lymphoma and given its limited
      toxicity, rituximab has been incorporated into HDT and ASCT for DLCL-B as in vivo
      purging, as part of high-dose regimens, and as maintenance therapy to prevent
      relapse. Preliminary results suggested that rituximab during ASCT and as
      maintenance therapy post-transplant reduces the risk of relapse and improves
      survival; however, these results need to be confirmed in phase III randomized
      trials. The role of ASCT during first remission as consolidative therapy in
      patients with DLCL-B remains controversial and should not be performed outside of
      the clinical trial setting. Allogeneic stem cell transplant (allo-SCT) for
      patients with relapsed DLCL-B is associated with significant toxicity and should
      be reserved for patients who relapse after ASCT or those with persistent marrow
      involvement. Innovative approaches are needed for primary refractory and
      chemoresistant relapsed DLCL-B since these patients have very poor outcomes after
      ASCT.

PMID- 17027659
TI  - New drugs for the treatment of advanced-stage diffuse large cell lymphomas.
AB  - The rapid pace of discovering new signaling pathways that influence the growth
      and survival of different types of cancer cells has produced a daunting array of
      potentially new, "drugable" targets for the treatment of cancer. This has been
      particularly true for the lymphomas. The empiric observation that many kinds of
      "novel targeted" drugs appear to exhibit relatively selective patterns of
      activity is testament to the concept that the lymphomas represent an incredibly
      diverse group of human cancers. Targeting one pathway in a subtype of lymphoma
      may not be universally effective against all subtypes of lymphoma, even closely
      related ones. These observations suggest that pharmacologically driven "target
      identification" plays an important role in the continued development of new
      therapeutic agents, and underscores the need for more research into the biologic
      basis for different subtypes of lymphoma. Over the past 10 years, there has been
      an explosion of new drugs making their way through preclinical laboratories and
      early clinical studies. These experiences have taught us some frustrating
      lessons. Sometimes, the strongest biologic rationale is associated with the
      poorest clinical results. Sometimes, where no rationale exists, golden
      therapeutic opportunities emerge. In either case, both experiences typically end
      up teaching us something about the disease we didn't historically appreciate. In
      this review, we will take a close look at some of the more intriguing targets in
      aggressive large B-cell lymphomas, all of which now have small molecules that can
      profoundly affect their activity, activity we hope will lead to new treatment
      opportunities. We will focus on the biologic rationale for targeting novel
      pathways regulated by Bcl-6, Bcl-2, BLysS, and APRIL for example. In addition, we
      will review how new concepts in structural biology and chemical design can help
      produce new generation compounds with novel activity, as is the case for
      pralatrexate and targeting the reduced folate carrier-type-1. Clearly, given the
      breadth and depth of information emerging on these and other relevant biologic
      pathways, we are limited to discussing only a few illustrative examples, which
      should in no way detract from the importance of other critical signaling and
      survival pathways now being exploited in the treatment of lymphoma.

PMID- 17027670
TI  - Tyramine in the assessment of regional adrenergic function.
AB  - Regional adrenergic function is difficult to assess in humans. Tyramine given
      through a microdialysis probe may be a useful tool in this regard. However,
      tyramine data is hard to interpret given the drug's complex mode of action. We
      characterized the response to tyramine, isoproterenol, and dopamine in adipose
      tissue with microdialysis probes in normal subjects. We measured glycerol
      concentrations to follow changes in lipolysis and monitored tissue perfusion with
      ethanol dilution. During perfusion with tyramine, dialysate glycerol
      concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/
      18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM
      at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response.
      A similar lipolytic response was not observed in isolated human adipocytes.
      Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however,
      dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine
      induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied
      through a microdialysis probe in concentrations up to 3.5 mM can be used to
      assess pre- and post-synaptic mechanisms regulating lipid mobilization.

PMID- 17027671
TI  - Modulation of extracellular matrix components by metalloproteinases and their
      tissue inhibitors during degeneration and regeneration of rat sural nerve.
AB  - The success of peripheral nervous system regeneration has been associated with
      changes on the microenvironment, particularly on the extracellular matrix (ECM)
      components. In the present study we analyzed by indirect immunohistochemistry,
      electron microscopy and Western blotting, the distribution of ECM components,
      metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), during Wallerian
      degeneration (WD) and nerve regeneration (2nd, 7th and 21st days after injury) on
      crushed rat sural nerves. Our results showed that laminin alpha3-chain and alpha2
      chain are over expressed during the early stages of degeneration and regeneration
      respectively, whereas type IV collagen expression increased progressively after
      crush. On the other hand, the expression of chondroitin sulfate was down
      regulated during the early stages of degeneration, returning progressively to
      normal values during nerve regeneration. The expression of MMP-3 was almost
      normal immediately after lesion, and then reduced progressively achieving the
      smallest expression at 21 days after crush; on the contrary, the expression of
      MMP-7 increased significantly immediately after crush (2nd day) returning to
      normal values afterwards. TIMP-1 and TIMP-2 were over expressed at the beginning
      of WD, returning progressively to normal values after that. These results
      indicate that the modifications of ECM components, which are favorable for nerve
      regeneration, are correlated with changes on the balance between MMPs and TIMPs.

PMID- 17027672
TI  - Combining motor training with transplantation of rat bone marrow stromal cells
      does not improve repair or recovery in rats with thoracic contusion injuries.
AB  - Previous studies have demonstrated that either transplantation of bone marrow
      stromal cells (MSC) or physical exercise regimens can elicit limited functional
      recovery following spinal cord injury, presumably through different mechanisms.
      The present study examined whether transplantation of MSC derived from transgenic
      Fischer alkaline phosphatase (AP) rats, in combination with exercise, would have
      synergistic effects leading to recovery of function that is greater than either
      alone. Adult female Sprague-Dawley rats received a moderate thoracic contusion
      injury and were divided into three groups: operated controls (Op-Control), MSC
      transplant recipients (MSC), and MSC transplant recipients plus exercise
      (MSC+Ex). Nine days after contusion, a Vitrogen matrix +/-one million MSC was
      injected into the lesion site in all animals. Immunosuppression with high doses
      of Cyclosporine A, required for MSC survival, was provided for all animals.
      Passive hindlimb exercise on motorized bicycles was applied 1 h/day, 3 days/week
      to the MSC+Ex group. A battery of behavioral tests was performed weekly to assess
      motor and sensory functions in all 3 groups for 12 weeks. Morphological
      evaluation included MSC survival, evidence of axonal growth into grafts,
      phenotypic analysis of MSC, and lesion/transplant size. The weight of the medial
      gastrocnemius muscle, a hindlimb muscle activated during stance, was used to
      identify extent of atrophy. No differences in motor recovery were found among the
      three groups. MSC survived 3 months after transplantation, indicating that the
      immunosuppression treatment was successful. The extent of survival was variable,
      and there was no correlation between MSC survival and behavioral scores. The
      matrix persisted, filling the lesion cavity, and some axons grew into the
      lesion/matrix but to a similar extent in all groups. There was no difference in
      lesion/matrix size among groups, indicating no neuroprotective effect on the host
      provided by the treatments. Immunocytochemical analysis provided no evidence that
      MSC differentiated into neurons, astrocytes or oligodendrocytes. Muscle mass of
      the medial gastrocnemius was diminished in the Op-Control group indicating
      significant atrophy, but was partially preserved in both the MSC and MSC+Ex
      groups. Our results indicate that combining the beneficial effects of rat MSC and
      this exercise protocol was not sufficient to enhance behavioral recovery.

PMID- 17027673
TI  - The relationship between electrophysiological correlates of recollection and
      amount of information retrieved.
AB  - The electrophysiological correlates of recollection were investigated with a
      modified Remember/Know task in which subjects signaled whether they fully or
      partially recollected visual object information in each study episode. A positive
      going ERP deflection--the left parietal old/new effect--was sensitive to the
      amount of information recollected, demonstrating greater amplitude when elicited
      by test items associated with full relative to partial recollection. These
      findings support prior proposals that the left parietal ERP old/new effect is
      sensitive to the amount of information recollected from episodic memory. An early
      onsetting (ca. 150 ms), left frontal old/new effect differentiated items accorded
      correct old versus correct new responses regardless of whether the items were
      endorsed as familiar or recollected. This finding extends the range of
      circumstances under which early, frontally distributed old/new effects occur, and
      adds weight to previous suggestions that these effects are a neural correlate of
      familiarity-driven recognition memory.

PMID- 17027674
TI  - G-protein coupled receptor kinase-like immunoreactivity in the snail, Helix
      pomatia, neurons.
AB  - GPRCs are regulated via phosphorylation by different protein kinases including
      GRKs and PKA and PKC. The purpose of this study was to determine the presence and
      physiological role of GRKs in the tissues of the snail, Helix pomatia. Here we
      report that immunoblotting of brain homogenate with anti-GRK2/3 antibody prepared
      from mammalian tissue can be detected in snail GRK-like immunoreactivity. The
      GRK2/3 immunoreactivity was found at approximately 80 kDa in a variety of cells,
      including salivary duct, salivary gland and eye. Intracellular injection of the
      anti-GRK2/3 prevented the neuron from desensitization and agonist-induced
      activation augmented the phosphorylated GRKs in the membrane fraction suggesting
      that GRKs may have a functional role in the neuropeptide receptor desensitization
      in snail.

PMID- 17027676
TI  - Wild plants and viruses: under-investigated ecosystems.

PMID- 17027677
TI  - Genetic diversity of plant virus populations: towards hypothesis testing in
      molecular epidemiology.

PMID- 17027678
TI  - Plant virus epidemiology: the concept of host genetic vulnerability.

PMID- 17027679
TI  - History and current distribution of begomoviruses in Latin America.

PMID- 17027680
TI  - Evolutionary epidemiology of plant virus disease.

PMID- 17027681
TI  - Control of plant virus diseases.

PMID- 17027682
TI  - Control of tropical plant virus diseases.

PMID- 17027683
TI  - Begomovirus evolution and disease management.

PMID- 17027684
TI  - Transgenic papaya: development, release, impact and challenges.

PMID- 17027685
TI  - Cassava mosaic virus disease in East and Central Africa: epidemiology and
      management of a regional pandemic.

PMID- 17027686
TI  - Host-plant viral infection effects on arthropod-vector population growth,
      development and behaviour: management and epidemiological implications.

PMID- 17027687
TI  - The migration of insect vectors of plant and animal viruses.

PMID- 17027689
TI  - Tissue preparation and banking.
AB  - With the increasing application of genomic and proteomic technologies to the
      research of neurological and psychiatric disorders it has become imperative that
      the postmortem tissue utilized be of the highest quality possible. Every step of
      the research design, from identifying donors, acquiring sufficient information
      for accurate diagnosis, to assessing tissue quality has to be carefully
      considered. In order to obtain high-quality RNA and protein from the postmortem
      brain tissue a standardized system of brain collection, dissection, and storage
      must be employed and key ante- and postmortem factors must be considered.
      Reliable RNA expression and protein data can be obtained from postmortem brains
      with relatively long postmortem intervals (PMIs) if the agonal factors and
      acidosis are not severe. While pH values are correlated with RNA integrity number
      (RIN), a higher pH does not guarantee intact RNA. Consequently RNA integrity must
      be assessed for every case before it is included in a study. An analysis of anti-
      and postmortem factors in a large brain collection has revealed that several
      diagnostic groups have significantly lower pH values than other groups, however,
      they do not have significantly lower RIN values. Moreover, the lower pH of these
      groups is not entirely due to agonal factors and/or smoking, indicating that
      these subjects may have additional metabolic abnormalities that contribute to the
      lower pH values.

PMID- 17027690
TI  - Functional genomic methodologies.
AB  - The ability to form tenable hypotheses regarding the neurobiological basis of
      normative functions as well as mechanisms underlying neurodegenerative and
      neuropsychiatric disorders is often limited by the highly complex brain circuitry
      and the cellular and molecular mosaics therein. The brain is an intricate
      structure with heterogeneous neuronal and nonneuronal cell populations dispersed
      throughout the central nervous system. Varied and diverse brain functions are
      mediated through gene expression, and ultimately protein expression, within these
      cell types and interconnected circuits. Large-scale high-throughput analysis of
      gene expression in brain regions and individual cell populations using modern
      functional genomics technologies has enabled the simultaneous quantitative
      assessment of dozens to hundreds to thousands of genes. Technical and
      experimental advances in the accession of tissues, RNA amplification
      technologies, and the refinement of downstream genetic methodologies including
      microarray analysis and real-time quantitative PCR have generated a wellspring of
      informative studies pertinent to understanding brain structure and function. In
      this review, we outline the advantages as well as some of the potential
      challenges of applying high throughput functional genomics technologies toward a
      better understanding of brain tissues and diseases using animal models as well as
      human postmortem tissues.

PMID- 17027691
TI  - Methods for proteomics in neuroscience.
AB  - Proteomics reveals complex protein expression, function, interactions and
      localization in different phenotypes of neuron. As proteomics, regarded as a
      highly complex screening technology, moves from a theoretical approach to
      practical reality, neuroscientists have to determine the most-appropriate
      applications for this technology. Even though proteomics compliments genomics, it
      is in sheer contrast to the basically constant genome due to its dynamic nature.
      Neuroscientists have to surmount difficulties particular to the research in
      neuroscience; such as limited sample amounts, heterogeneous cellular compositions
      in samples and the fact that many proteins of interest are hydrophobic proteins.
      The necessity of exclusive technology, sophisticated software and skilled
      manpower tops the challenge. This review examines subcellular organelle
      isolation, protein fractionation and separation using two-dimensional gel
      electrophoresis (2-DGE) as well as multi-dimensional liquid chromatography (LC)
      followed by mass spectrometry (MS). The methods for quantifying relative gene
      product expression between samples (e.g., two-dimensional difference in gel
      electrophoresis (2D-DIGE), isotope-coded affinity tag (ICAT) and iTRAQ) are
      elaborated. An overview of the techniques used currently to assign post
      translational modification status on a proteomics scale is also evaluated. The
      feasible coverage of the proteome, ability to detect unique cell components such
      as post-synaptic densities and membrane proteins, resource requirements and
      quantitative as well as qualitative reliability of different approaches is also
      discussed. While there are many challenges in neuroproteomics, this field
      promises many returns in the future.

PMID- 17027692
TI  - Functional genomics and proteomics in the clinical neurosciences: data mining and
      bioinformatics.
AB  - The goal of this chapter is to introduce some of the available computational
      methods for expression analysis. Genomic and proteomic experimental techniques
      are briefly discussed to help the reader understand these methods and results
      better in context with the biological significance. Furthermore, a case study is
      presented that will illustrate the use of these analytical methods to extract
      significant biomarkers from high-throughput microarray data. Genomic and
      proteomic data analysis is essential for understanding the underlying factors
      that are involved in human disease. Currently, such experimental data are
      generally obtained by high-throughput microarray or mass spectrometry
      technologies among others. The sheer amount of raw data obtained using these
      methods warrants specialized computational methods for data analysis. Biomarker
      discovery for neurological diagnosis and prognosis is one such example. By
      extracting significant genomic and proteomic biomarkers in controlled
      experiments, we come closer to understanding how biological mechanisms contribute
      to neural degenerative diseases such as Alzheimers' and how drug treatments
      interact with the nervous system. In the biomarker discovery process, there are
      several computational methods that must be carefully considered to accurately
      analyze genomic or proteomic data. These methods include quality control,
      clustering, classification, feature ranking, and validation. Data quality control
      and normalization methods reduce technical variability and ensure that discovered
      biomarkers are statistically significant. Preprocessing steps must be carefully
      selected since they may adversely affect the results of the following expression
      analysis steps, which generally fall into two categories: unsupervised and
      supervised. Unsupervised or clustering methods can be used to group similar
      genomic or proteomic profiles and therefore can elucidate relationships within
      sample groups. These methods can also assign biomarkers to sub-groups based on
      their expression profiles across patient samples. Although clustering is useful
      for exploratory analysis, it is limited due to its inability to incorporate
      expert knowledge. On the other hand, classification and feature ranking are
      supervised, knowledge-based machine learning methods that estimate the
      distribution of biological expression data and, in doing so, can extract
      important information about these experiments. Classification is closely coupled
      with feature ranking, which is essentially a data reduction method that uses
      classification error estimation or other statistical tests to score features.
      Biomarkers can subsequently be extracted by eliminating insignificantly ranked
      features. These analytical methods may be equally applied to genetic and
      proteomic data. However, because of both biological differences between the data
      sources and technical differences between the experimental methods used to obtain
      these data, it is important to have a firm understanding of the data sources and
      experimental methods. At the same time, regardless of the data quality, it is
      inevitable that some discovered biomarkers are false positives. Thus, it is
      important to validate discovered biomarkers. The validation process may be slow;
      yet, the overall biomarker discovery process is significantly accelerated due to
      initial feature ranking and data reduction steps. Information obtained from the
      validation process may also be used to refine data analysis procedures for future
      iteration. Biomarker validation may be performed in a number of ways - bench-side
      in traditional labs, web-based electronic resources such as gene ontology and
      literature databases, and clinical trials.

PMID- 17027693
TI  - Reproducibility of microarray studies: concordance of current analysis methods.

PMID- 17027694
TI  - The genomics of mood disorders.

PMID- 17027695
TI  - Transcriptome alterations in schizophrenia: disturbing the functional
      architecture of the dorsolateral prefrontal cortex.
AB  - The availability of methods for quantifying tissue concentrations of messenger
      RNAs in the postmortem of the human brain has provided a number of new findings
      in schizophrenia. However, understanding how these findings actually relate to
      the disease process of schizophrenia requires knowledge both of the factors that
      might give rise to such changes in gene expression and of the impact of these
      changes on the function of the affected neural circuits. Consequently, this
      chapter provides a review of the potential causes and consequences of some of the
      schizophrenia-related transcriptome changes in the dorsolateral prefrontal
      cortex, a brain region implicated in the pathophysiology of certain core
      cognitive deficits in this illness.

PMID- 17027696
TI  - Strategies for improving sensitivity of gene expression profiling: regulation of
      apoptosis in the limbic lobe of schizophrenics and bipolars.

PMID- 17027698
TI  - Neuronal gene expression profiling: uncovering the molecular biology of
      neurodegenerative disease.
AB  - The development of gene array techniques to quantify expression levels of dozens
      to thousands of genes simultaneously within selected tissue samples from control
      and diseased brain has enabled researchers to generate expression profiles of
      vulnerable neuronal populations in several neurodegenerative diseases, including
      Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, and
      Creutzfeld-Jakob disease. Intriguingly, gene expression analysis reveals that
      vulnerable brain regions in many of these diseases share putative pathogenetic
      alterations in common classes of genes, including decrements in synaptic
      transcript levels and increments in immune response transcripts. Thus, gene
      expression profiles of diseased neuronal populations may reveal mechanistic clues
      to the molecular pathogenesis underlying various neurological diseases and aid in
      identifying potential therapeutic targets. This chapter will review how regional
      and single cell gene array technologies have advanced our understanding of the
      genetics of human neurological disease.

PMID- 17027697
TI  - Assessment of genome and proteome profiles in cocaine abuse.
AB  - Until recently, knowledge of the impact of abuse drugs on gene and protein
      expression in the brain was limited to less than 100 targets. With the advent of
      high-throughput genomic and proteomic techniques investigators are now able to
      evaluate changes across the entire genome and across thousands of proteins in
      defined brain regions and generate expression profiles of vulnerable
      neuroanatomical substrates in rodent and non-human primate drug abuse models and
      in human post-mortem brain tissue from drug abuse victims. The availability of
      gene and protein expression profiles will continue to expand our understanding of
      the short- and long-term consequences of drug addiction and other addictive
      disorders and may provide new approaches or new targets for pharmacotherapeutic
      intervention. This chapter will review gene expression data from rodent, non
      human primate and human post-mortem studies of cocaine abuse and will provide a
      preliminary proteomic profile of human cocaine abuse and explore how these
      studies have advanced our understanding of addiction.

PMID- 17027699
TI  - Epileptogenesis-related genes revisited.
AB  - The main goal of this study was to identify common features in the molecular
      response to epileptogenic stimuli across different animal models of
      epileptogenesis. Therefore, we compared the currently available literature on the
      global analysis of gene expression following epileptogenic insult to search for
      (i) highly represented functional gene classes (GO terms) within data sets, and
      (ii) individual genes that appear in several data sets, and therefore, might be
      of particular importance for the development of epilepsy due to different
      etiologies. We focused on two well-described models of brain insult that induce
      the development of spontaneous seizures in experimental animals: status
      epilepticus and traumatic brain injury. Additionally, a few papers describing
      gene expression in rat and human epileptic tissue were included for comparison.
      Our analysis revealed that epileptogenic insults induce significant changes in
      gene expression within a subset of pre-defined GO terms, that is, in groups of
      functionally linked genes. We also found individual genes for which expression
      changed across different models of epileptogenesis. Alterations in gene
      expression appear time-specific and underlie a number of processes that are
      linked with epileptogenesis, such as cell death and survival, neuronal
      plasticity, or immune response. Particularly, our analysis highlighted
      alterations in gene expression in glial cells as well as in genes involved in the
      immune response, which suggests the importance of gliosis and immune reaction in
      epileptogenesis.

PMID- 17027700
TI  - Functional genomics of sex hormone-dependent neuroendocrine systems: specific and
      generalized actions in the CNS.
AB  - Sex hormone effects on hypothalamic neurons have been worked out to a point where
      receptor mechanisms are relatively well understood, a neural circuit for a sex
      steroid-dependent behavior has been determined, and several functional genomic
      regulations have been discovered and conceptualized. With that knowledge in hand,
      we approach deeper problems of explaining sexual arousal and generalized CNS
      arousal. After a brief summary of arousal mechanisms, we focus on three chemical
      systems which signal generalized arousal and impact hormone-dependent
      hypothalamic neurons of behavioral importance: histamine, norepinephrine and
      enkephalin.

PMID- 17027701
TI  - Implications for the practice of psychiatry.

PMID- 17027702
TI  - Human brain evolution.

PMID- 17027703
TI  - N-acetylgalactosamine-6-sulfatase protein detection in MPS IVA patient and
      unaffected control samples.
AB  - BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome) is a
      lysosomal storage disorder caused by a deficiency in the activity of the
      lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS). MPS IVA patients
      can present with severe myelopathy, hearing loss, heart valve involvement, short
      trunk/dwarfism and corneal clouding. Early diagnosis of MPS IVA will allow
      potential treatments to be implemented before the onset of irreversible
      pathology. METHODS: We have developed a sensitive immune-quantification assay for
      the accurate detection of GALNS protein in skin fibroblasts, blood and plasma
      from unaffected control and MPS IVA patients. RESULTS: MPS IVA patient fibroblast
      extracts (n=11) had non-detectable (ND)-10 ng/mg of 6-sulfatase protein compared
      to 3-82 ng/mg for normal controls (n=19). Dried blood-spots from MPS IVA patients
      (n=4) contained ND-1.3 ng/L of 6-sulfatase protein compared to 18-145 ng/L for
      normal controls (n=49). Plasma from MPS IVA patients (n=7) contained ND 6
      sulfatase protein compared to 1-9 ng/L for normal controls (n=49). CONCLUSIONS:
      The immune assay described here had the capacity to accurately measure the amount
      of GALNS protein in various biological samples, providing the basis of an assay
      that could be further developed to enable newborn and high-risk population
      screening for MPS IVA patients.

PMID- 17027704
TI  - Institute of Medicine urges reforms at FDA.

PMID- 17027705
TI  - Should HPV vaccines be mandatory for all adolescents?

PMID- 17027706
TI  - Water and sanitation: the neglected health MDG.

PMID- 17027707
TI  - The next Director-General of WHO.

PMID- 17027708
TI  - SPACE: not the final frontier.

PMID- 17027709
TI  - Misoprostol for preventing PPH: some lessons learned.

PMID- 17027710
TI  - Glucose lowering and diabetes prevention: are they the same?

PMID- 17027711
TI  - The definition of disability: what is in a name?

PMID- 17027712
TI  - Rising to the global challenge of the chronic disease epidemic.

PMID- 17027713
TI  - Institutional reviews and innovation in clinical research.

PMID- 17027715
TI  - Lawrence K Altman.

PMID- 17027716
TI  - Are statins analogues of vitamin D?

PMID- 17027717
TI  - Are statins analogues of vitamin D?

PMID- 17027718
TI  - Are statins analogues of vitamin D?

PMID- 17027719
TI  - Are statins analogues of vitamin D?

PMID- 17027720
TI  - Smoking and age-related maculopathies.

PMID- 17027721
TI  - Treatment of age-related macular degeneration.

PMID- 17027723
TI  - Toronto AIDS conference: where were the children?

PMID- 17027724
TI  - Cautious optimism for new HIV/AIDS prevention strategies.

PMID- 17027725
TI  - Killer fentanyl: a lesson from anaesthesiology.

PMID- 17027726
TI  - Confusion begets confusion.

PMID- 17027727
TI  - Bad sex.

PMID- 17027729
TI  - 30 day results from the SPACE trial of stent-protected angioplasty versus carotid
      endarterectomy in symptomatic patients: a randomised non-inferiority trial.
AB  - BACKGROUND: Carotid endarterectomy is effective in stroke prevention for patients
      with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has
      been widely used as alternative treatment. Since equivalence or superiority has
      not been convincingly shown for either treatment, we aimed to compare the two.
      METHODS: 1200 patients with symptomatic carotid-artery stenosis were randomly
      assigned within 180 days of transient ischaemic attack or moderate stroke
      (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or
      carotid endarterectomy (n=595). The primary endpoint of this hospital-based study
      was ipsilateral ischaemic stroke or death from time of randomisation to 30 days
      after the procedure. The non-inferiority margin was defined as less than 2.5% on
      the basis of an expected event rate of 5%. Analyses were on an intention-to-treat
      basis. This trial is registered at Current Controlled Trials with the
      international standard randomised controlled trial number ISRCTN57874028.
      FINDINGS: 1183 patients were included in the analysis. The rate of death or
      ipsilateral ischaemic stroke from randomisation to 30 days after the procedure
      was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy
      (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for
      non-inferiority is 0.09. INTERPRETATION: SPACE failed to prove non-inferiority of
      carotid-artery stenting compared with carotid endarterectomy for the
      periprocedural complication rate. The results of this trial do not justify the
      widespread use in the short-term of carotid-artery stenting for treatment of
      carotid-artery stenoses. Results at 6-24 months are awaited.

PMID- 17027730
TI  - Oral misoprostol in preventing postpartum haemorrhage in resource-poor
      communities: a randomised controlled trial.
AB  - BACKGROUND: Postpartum haemorrhage is a major cause of maternal mortality in the
      developing world. Although effective methods for prevention and treatment of such
      haemorrhage exist--such as the uterotonic drug oxytocin--most are not feasible in
      resource-poor settings where many births occur at home. We aimed to investigate
      whether oral misoprostol, a potential alternative to oxytocin, could prevent
      postpartum haemorrhage in a community home-birth setting. METHODS: In a placebo
      controlled trial undertaken between September, 2002, and December, 2005, 1620
      women in rural India were randomised to receive oral misoprostol (n=812) or
      placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the
      deliveries, administered the study drug, and measured blood loss. The primary
      outcome was the incidence of acute postpartum haemorrhage (defined as > or =500
      mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The
      trial was registered with the US clinical trials database (http://www.
      clinicaltrials.gov) as number NCT00097123. FINDINGS: Oral misoprostol was
      associated with a significant reduction in the rate of acute postpartum
      haemorrhage (12.0% to 6.4%, p<0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and
      acute severe postpartum haemorrhage (1.2% to 0.2%, p<0.0001; 0.20 [0.04-0.91].
      One case of postpartum haemorrhage was prevented for every 18 women treated.
      Misoprostol was also associated with a decrease in mean postpartum blood loss
      (262.3 mL to 214.3 mL, p<0.0001). Postpartum haemorrhage rates fell over time in
      both groups but remained significantly higher in the placebo group. Women taking
      misoprostol had a higher rate of transitory symptoms of chills and fever than the
      control. INTERPRETATION: Oral misoprostol was associated with significant
      decreases in the rate of acute postpartum haemorrhage and mean blood loss. The
      drug's low cost, ease of administration, stability, and a positive safety profile
      make it a good option in resource-poor settings.

PMID- 17027731
TI  - Short-term risk of AIDS or death in people infected with HIV-1 before
      antiretroviral therapy in South Africa: a longitudinal study.
AB  - BACKGROUND: In sub-Saharan Africa, data for short-term risk of AIDS or death,
      which might inform decisions about when to start antiretroviral therapy (ART),
      are scarce. Our aim was to investigate these risks in patients who had no access
      to ART or who were given zidovudine alone. METHODS: 6-month risks (%) of death,
      AIDS, and combined risk of AIDS and death (AIDS/death) were calculated according
      to CD4-cell count category of less than 200 cells per microL, 200-350 cells per
      microL, or greater than 350 cells per microL, stratified by WHO clinical stages 1
      and 2 combined, 3, or 4 in untreated patients (n=1399) seeking care in tertiary
      public-sector HIV clinics before widespread availability of ART in Cape Town,
      South Africa. FINDINGS: Risk of death for WHO stages 1 and 2 was 3.5% for those
      with less than 200 cells per microL, 2.8% for 200-350 cells per microL, and 1.2%
      for greater than 350 cells per microL. The corresponding rates for WHO stage 3
      were 10.8%, 4.3%, and 4.9% and for stage 4, 22.2%, 10.3%, and 13.8%. 52% (90) of
      deaths took place in patients without AIDS. 6-month risk of AIDS for WHO stages 1
      and 2 was 3.5% for those with less than 200 cells per microL, 1.6% for 200-350
      cells per microL, and zero for greater than 350 cells per microL. The
      corresponding rates for those with WHO stage 3 disease were 17.4%, 7.0%, and
      2.2%. INTERPRETATION: In this study, risk of AIDS in patients with a CD4-cell
      count of less than 200 cells per microL or greater than 350 cells per microL was
      similar to that previously reported from European cohorts, but was 1.9 times
      greater for those with CD4-cell counts of between 200 and 350 cells per microL.
      The high death rate before development of AIDS and a high risk of AIDS in those
      with CD4-cell counts of 200-350 cells per microL indicate that delay in
      initiation of ART is associated with increased morbidity and mortality. These
      findings might help to amend criteria for start of ART in resource-limited
      settings.

PMID- 17027732
TI  - Prevalence of intimate partner violence: findings from the WHO multi-country
      study on women's health and domestic violence.
AB  - BACKGROUND: Violence against women is a serious human rights abuse and public
      health issue. Despite growing evidence of the size of the problem, current
      evidence comes largely from industrialised settings, and methodological
      differences limit the extent to which comparisons can be made between studies. We
      aimed to estimate the extent of physical and sexual intimate partner violence
      against women in 15 sites in ten countries: Bangladesh, Brazil, Ethiopia, Japan,
      Namibia, Peru, Samoa, Serbia and Montenegro, Thailand, and the United Republic of
      Tanzania. METHODS: Standardised population-based household surveys were done
      between 2000 and 2003. Women aged 15-49 years were interviewed and those who had
      ever had a male partner were asked in private about their experiences of
      physically and sexually violent and emotionally abusive acts. FINDINGS: 24,097
      women completed interviews, with around 1500 interviews per site. The reported
      lifetime prevalence of physical or sexual partner violence, or both, varied from
      15% to 71%, with two sites having a prevalence of less than 25%, seven between
      25% and 50%, and six between 50% and 75%. Between 4% and 54% of respondents
      reported physical or sexual partner violence, or both, in the past year. Men who
      were more controlling were more likely to be violent against their partners. In
      all but one setting women were at far greater risk of physical or sexual violence
      by a partner than from violence by other people. INTERPRETATION: The findings
      confirm that physical and sexual partner violence against women is widespread.
      The variation in prevalence within and between settings highlights that this
      violence in not inevitable, and must be addressed.

PMID- 17027733
TI  - Persistent left superior vena cava into left atrium.

PMID- 17027734
TI  - Necrotising enterocolitis.
AB  - Necrotising enterocolitis is one of the most common gastrointestinal emergencies
      in newborn infants. Here we review the epidemiology, clinical presentation, and
      pathophysiology of the disease, as well as strategies for diagnosis, management,
      and prevention. Necrotising enterocolitis is one of the most devastating and
      unpredictable diseases affecting premature infants. Despite decades of research,
      its pathogenesis remains unclear; diagnosis can be difficult; and treatment is
      challenging. We will need to improve our understanding of intestinal defences in
      premature infants, dietary and bacterial factors, and genetic effects that could
      predispose infants to necrotising enterocolitis before we can develop new
      strategies for prevention and treatment.

PMID- 17027735
TI  - Strategies for reducing maternal mortality: getting on with what works.
AB  - The concept of knowing what works in terms of reducing maternal mortality is
      complicated by a huge diversity of country contexts and of determinants of
      maternal health. Here we aim to show that, despite this complexity, only a few
      strategic choices need to be made to reduce maternal mortality. We begin by
      presenting the logic that informs our strategic choices. This logic suggests that
      implementation of an effective intrapartum-care strategy is an overwhelming
      priority. We also discuss the alternative configurations of such a strategy and,
      using the best available evidence, prioritise one strategy based on delivery in
      primary-level institutions (health centres), backed up by access to referral
      level facilities. We then go on to discuss strategies that complement intrapartum
      care. We conclude by discussing the inexplicable hesitation in decision-making
      after nearly 20 years of safe motherhood programming: if the fifth Millennium
      Development Goal is to be achieved, then what needs to be prioritised is obvious.
      Further delays in getting on with what works begs questions about the commitment
      of decision-makers to this goal.

PMID- 17027736
TI  - Benign intraspinal tumour misdiagnosed as mechanical low back pain.

PMID- 17027737
TI  - Belief-desire reasoning in the explanation of behavior: do actions speak louder
      than words?
AB  - The mechanisms underwriting our commonsense psychology, or 'theory of mind', have
      been extensively investigated via reasoning tasks that require participants to
      predict the action of agents based on information about beliefs and desires.
      However, relatively few studies have investigated the processes contributing to a
      central component of 'theory of mind' - our ability to explain the action of
      agents in terms of underlying beliefs and desires. In two studies, we demonstrate
      a novel phenomenon in adult belief-desire reasoning, capturing the folk notion
      that 'actions speak louder than words'. When story characters were described as
      searching in the wrong place for a target object, adult subjects often endorsed
      mental state explanations referencing a distracter object, but only when that
      object was approached. We discuss how this phenomenon, alongside other reasoning
      "errors" (e.g., hindsight bias; the curse of knowledge) can be used to illuminate
      the architecture of domain specific belief-desire reasoning processes.

PMID- 17027738
TI  - The role of the SCRAMBLED receptor-like kinase in patterning the Arabidopsis root
      epidermis.
AB  - Cell-type patterning in the Arabidopsis root epidermis is achieved by a network
      of transcription factors and influenced by a position-dependent mechanism. The
      SCRAMBLED receptor-like kinase is required for the normal pattern to arise, but
      its precise role is not understood. Here we describe genetic and molecular
      studies to define the spatial and temporal role of SCM in epidermal patterning
      and its relationship to the transcriptional network. Our results suggest that SCM
      helps unspecified epidermal cells interpret their position in relation to the
      underlying cortical cells and establish distinct cell identities. Furthermore,
      SCM loss-of-function and overexpression analyses suggest that SCM influences cell
      fate through its negative transcriptional regulation of the WEREWOLF MYB gene in
      epidermal cells at the H position. We also find that SCM function is specifically
      required for patterning the post-embryonic root epidermis and not for the
      analogous epidermal cell-type patterning during embryogenesis or hypocotyl
      development. In addition, we show that two closely related SCM-like genes in
      Arabidopsis (SRF1 and SRF3) are not required alone or together with SCM for
      proper epidermal patterning. These findings help define the developmental and
      mechanistic role of SCM and suggest a new model for its action in root epidermal
      cell patterning.

PMID- 17027739
TI  - The immune gene repertoire encoded in the purple sea urchin genome.
AB  - Echinoderms occupy a critical and largely unexplored phylogenetic vantage point
      from which to infer both the early evolution of bilaterian immunity and the
      underpinnings of the vertebrate adaptive immune system. Here we present an
      initial survey of the purple sea urchin genome for genes associated with
      immunity. An elaborate repertoire of potential immune receptors, regulators and
      effectors is present, including unprecedented expansions of innate pathogen
      recognition genes. These include a diverse array of 222 Toll-like receptor (TLR)
      genes and a coordinate expansion of directly associated signaling adaptors.
      Notably, a subset of sea urchin TLR genes encodes receptors with structural
      characteristics previously identified only in protostomes. A similarly expanded
      set of 203 NOD/NALP-like cytoplasmic recognition proteins is present. These genes
      have previously been identified only in vertebrates where they are represented in
      much lower numbers. Genes that mediate the alternative and lectin complement
      pathways are described, while gene homologues of the terminal pathway are not
      present. We have also identified several homologues of genes that function in
      jawed vertebrate adaptive immunity. The most striking of these is a gene cluster
      with similarity to the jawed vertebrate Recombination Activating Genes 1 and 2
      (RAG1/2). Sea urchins are long-lived, complex organisms and these findings reveal
      an innate immune system of unprecedented complexity. Whether the presumably
      intense selective processes that molded these gene families also gave rise to
      novel immune mechanisms akin to adaptive systems remains to be seen. The genome
      sequence provides immediate opportunities to apply the advantages of the sea
      urchin model toward problems in developmental and evolutionary immunobiology.

PMID- 17027740
TI  - The sea urchin kinome: a first look.
AB  - This paper reports a preliminary in silico analysis of the sea urchin kinome. The
      predicted protein kinases in the sea urchin genome were identified, annotated and
      classified, according to both function and kinase domain taxonomy. The results
      show that the sea urchin kinome, consisting of 353 protein kinases, is closer to
      the Drosophila kinome (239) than the human kinome (518) with respect to total
      kinase number. However, the diversity of sea urchin kinases is surprisingly
      similar to humans, since the urchin kinome is missing only 4 of 186 human
      subfamilies, while Drosophila lacks 24. Thus, the sea urchin kinome combines the
      simplicity of a non-duplicated genome with the diversity of function and
      signaling previously considered to be vertebrate-specific. More than half of the
      sea urchin kinases are involved with signal transduction, and approximately 88%
      of the signaling kinases are expressed in the developing embryo. These results
      support the strength of this nonchordate deuterostome as a pivotal developmental
      and evolutionary model organism.

PMID- 17027741
TI  - Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by
      integrin signaling that targets phospholipase C.
AB  - Integrin signaling modulates trophoblast adhesion to extracellular matrices
      during blastocyst implantation. Fibronectin (FN)-binding activity on the apical
      surface of trophoblast cells is strengthened after elevation of intracellular
      Ca(2+) downstream of integrin ligation by FN. We report here that
      phosphoinositide-specific phospholipase C (PLC) mediates Ca(2+) signaling in
      response to FN. Pharmacological agents used to antagonize PLC (U73122) or the
      inositol phosphate receptor (Xestospongin C) inhibited FN-induced elevation of
      intracellular Ca(2+) and prevented the upregulation of FN-binding activity. In
      contrast, inhibitors of Ca(2+) influx through either voltage-gated or non-voltage
      gated Ca(2+) channels were without effect. Inhibition of protein tyrosine kinase
      activity by genistein, but not G-protein inhibition by suramin, blocked FN
      induced intracellular Ca(2+) signaling and upregulation of adhesion, consistent
      with involvement of PLC-gamma. Confocal immunofluorescence imaging of peri
      implantation blastocysts demonstrated that PLC-gamma2, but not PLC-gamma1 nor PLC
      beta1, accumulated near the outer surface of the embryo. Phosphotyrosine site
      directed antibodies revealed phosphorylation of PLC-gamma2, but not PLC-gamma1,
      upon integrin ligation by FN. These data suggest that integrin-mediated
      activation of PLC-gamma to initiate phosphoinositide signaling and intracellular
      Ca(2+) mobilization is required for blastocyst adhesion to FN. Signaling cascades
      regulating PLC-gamma could, therefore, control a critical feature of trophoblast
      differentiation during peri-implantation development.

PMID- 17027742
TI  - Ginsenoside Re of Panax ginseng possesses significant antioxidant and
      antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is characterized by hyperglycemia and complications affecting
      the eye, kidney, nerve and blood vessel. We have previously demonstrated the
      occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded
      by a depletion in the tissue level of glutathione. In this study, when diabetic
      rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a
      significant reduction in blood glucose, total cholesterol and triglyceride
      levels. On the other hand, oxidative stress has been implicated in the
      pathogenesis of diabetes and its complications. It was found that treatment by
      ginsenoside Re restored the levels of both glutathione and malondialdehyde in the
      eye and kidney to those found in the control rats. This is the first report
      demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes,
      and prevents the onset of oxidative stress in some vascular tissues. Our results
      demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and
      exerts protective actions against the occurrence of oxidative stress in the eye
      and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re
      could be used as an effective antidiabetic agent particularly in the prevention
      of diabetic microvasculopathy.

PMID- 17027743
TI  - Fluorescence- and luminescence-based methods for the determination of affinity
      and activity of neuropeptide Y2 receptor ligands.
AB  - With respect to the discovery and characterization of neuropeptide Y(2) receptor
      ligands as pharmacological tools or potential drugs, fluorescence- and
      luminescence-based assays were developed to determine both the affinity and the
      activity of receptor agonists and antagonists. A flow cytometric binding assay is
      described for the hY(2) receptor stably expressed in CHO cells using cy5-labeled
      porcine neuropeptide Y and compared with a radioligand binding assay. Binding of
      the fluorescent ligand was visualized by confocal microscopy. Stable co
      transfection with the chimeric G protein Gq(i5) enabled the establishment of a
      spectrofluorimetric fura-2 and a flow cytometric fluo-4 calcium assay. Further
      stable expression of apoaequorin targeted to the mitochondria allowed the
      establishment of an aequorin assay which could be performed in the 96-well
      format. The shape of the concentration-response curves of porcine neuropeptide Y
      in the presence of the Y(2)-selective receptor antagonist BIIE0246,
      characteristic of either competitive or insurmountable antagonism, depended on
      the period of incubation with the cells. Functional data of Y(2) receptor
      agonists and antagonists determined in the fluorescence- and luminescence-based
      assays were in good agreement.

PMID- 17027744
TI  - Synergistic antinociceptive effects of anandamide, an endocannabinoid, and
      nonsteroidal anti-inflammatory drugs in peripheral tissue: a role for endogenous
      fatty-acid ethanolamides?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit fatty-acid amide hydrolase
      (FAAH), the enzyme responsible for the metabolism of anandamide, an
      endocannabinoid. It has been suggested that the mechanisms of action of NSAIDs
      could be due to inhibition of cyclooxygenase (COX) and also to an increase in
      endocannabinoid concentrations. In a previous study we have demonstrated that the
      local analgesic interaction between anandamide and ibuprofen (a non-specific COX
      inhibitor) was synergistic for the acute and inflammatory phases of the formalin
      test. To test this hypothesis further, we repeated similar experiments with
      rofecoxib (a selective COX-2 inhibitor) and also measured the local
      concentrations of anandamide, and of two fatty-acid amides, oleoylethanolamide
      and palmitoylethanolamide. We established the ED(50) for anandamide (34.52 pmol+/
      17.26) and rofecoxib (381.72 pmol+/-190.86) and showed that the analgesic effect
      of the combination was synergistic. We also found that paw tissue levels of
      anandamide, oleoylethanolamide and palmitoylethanolamide were significantly
      higher when anandamide was combined with NSAIDs and that this effect was greater
      with rofecoxib. In conclusion, local injection of anandamide or rofecoxib was
      antinociceptive in a test of acute and inflammatory pain and the combination of
      anandamide with rofecoxib was synergistic. Finally, locally injected anandamide
      with either NSAID (ibuprofen or rofecoxib) generates higher amount of fatty-acid
      ethanolamides. The exact comprehension of the mechanisms involved needs further
      investigation.

PMID- 17027745
TI  - Montmorillonite ameliorates hyperthyroidism of rats and mice attributed to its
      adsorptive effect.
AB  - The present study aims to evaluate the adsorbing effect of montmorillonite on
      thyroid hormone in the entero-hepatic circulation. The concentration of thyroid
      hormone in the serum of hyperthyroidism model rats and in solution was measured
      by radioimmunoassay and ultraviolet spectrometry, respectively. The body weight,
      temperature, and consumption of food and water were observed in hyperthyroidism
      model rats. Furthermore, hypoxia tolerance, sodium-pentobarbital-induced sleep
      time, spontaneous activities were measured on hyperthyroidism model mice after
      being treated with montmorillonite. Results showed that montmorillonite adsorbed
      thyroxin (T(4)) and triiodothyronine (T(3)) in vitro. Montmorillonite at dosage
      of 1.0 g/kg and 0.3 g/kg decreased thyroid hormone levels on hyperthyroidism
      model rats; Montmorillonite (2.0 g/kg and 0.6 g/kg) prolonged the sleep time,
      improved the hypoxia tolerant capacity and reduced the spontaneous activities of
      the hyperthyroidism model mice. These results suggest montmorillonite has anti
      hyperthyroidism effect attributed to its adsorptive effect.

PMID- 17027746
TI  - Cardio-protective role of terazosin is possibly mediated through alteration in
      thyroid function.
AB  - An investigation was made to reveal the possible involvement of thyroid hormones,
      if any, in terazosin (an alfa-1 adrenergic receptor blocker) induced alterations
      in tissue lipid peroxidation (LPO) and in the concentration of different serum
      lipids. We determined the impact of terazosin on the changes in
      hypercholesterolemic (CCT) diet induced thyroid dysfunction; cardiac, renal and
      hepatic LPO and on serum glucose concentration in female Wister rats.
      Simultaneously levels of total cholesterol (TC), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides
      (TG), creatinine, alkaline phosphatase (ALP) activity, hepatic glycogen synthesis
      and total daily food consumption were studied as supporting parameters. While a
      decrease in the level of serum thyroid hormones, HDL-C and in hepatic glycogen
      content, was observed in CCT diet fed animals; it increased the concentration of
      other serum lipids, glucose and creatinine; ALP activity; tissue and serum LPO.
      However, following terazosin administration for 15 days to CCT diet fed animals,
      status of thyroid hormones and all other thyroid dependent parameters were
      reversed suggesting that the drug might be acting through an alteration in the
      thyroid functions.

PMID- 17027747
TI  - Selective antagonism activity of alkaloids from bulbs Fritillariae at muscarinic
      receptors: functional studies.
AB  - 15 alkaloids were isolated from five Fritillariae species and 6 derivatives were
      synthesized. Alkaloids having anticholinergic effect on guinea-pig tracheal
      smooth muscle were screened out and their mechanism was further studied on the
      cAMP formation in Chinese hamster ovary cells stably expressing human muscarinic
      M2 receptor (CHO-hM2 cells) and intracellular calcium ([Ca(2+)](i)) transient in
      Chinese hamster ovary cells stably expressing human muscarinic M3 receptor (CHO
      hM3 cells). In normal Krebs-Henseleit (KH) solution, imperialine (15), 3beta
      acetylimperialine (16) and sinpeinine A (17) concentration-dependently relaxed 1
      microM carbachol-induced contraction of guinea-pig tracheal rings with EC(50) of
      4.19, 1.71 and 4.67 microM, respectively. In Ca(2+)-free KH solution, 10 microM
      3beta-acetylimperialine (16), imperialine (15) and sinpeinnine A (17) caused
      97.42%, 5.45% and 6.55% inhibition, respectively, which indicated that the three
      components might inhibit muscarinic receptor in different mechanism. Results of
      muscarinic M2 receptor-inhibited cAMP formation in CHO-hM2 cells showed that
      imperialine (15) and sinpeinine A (17) could potently elevate the cAMP formation
      whereas 3beta-acetylimperialine (16) only had weak effect on antagonism of cAMP
      inhibition. Furthermore, the investigations of muscarinic M3 receptor-stimulated
      [Ca(2+)](i) transient in CHO-hM3 cells revealed that imperialine (15) and
      sinpeinine A (17) could not antagonize [Ca(2+)](i) transient, but 3beta
      acetylimperialine (16) significantly inhibited [Ca(2+)](i) peak elevation with an
      IC(50) of 5.26 microM. The functional studies suggest that the mechanism of
      relaxant action of imperialine (15) and sinpeinine A (17) is due to their
      selective inhibitory effects on muscarinic M2 receptors and the mechanism of
      3beta-acetylimperialine (16) originates from its selective muscarinic M3
      receptors antagonism.

PMID- 17027748
TI  - 4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by
      inhibiting NF-kappaB-DNA-binding activity.
AB  - We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a
      major metabolite of gallic acid abundant in red wine, on vascular inflammation
      and its action mechanism. 4-OMGA inhibited the expression of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis
      factor-alpha (TNF-alpha), resulting in the suppression of leukocyte adhesion to
      HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM
      1 and the activity of nuclear factor-kappaB (NF-kappaB) without affecting
      cytosolic IkappaB kinase (IKK) activation, inhibitor of kappaB (IkappaB)
      phosphorylation and degradation, and nuclear translocation of NF-kappaB. This
      compound did not alter nitric oxide (NO) generation, but inhibited reactive
      oxygen species (ROS) production in TNF-alpha-stimulated HUVECs, suggesting that
      NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-kappaB activity.
      Moreover, 4-OMGA directly blocked the binding activity of NF-kappaB to its
      consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from
      TNF-alpha-stimulated HUVECs, but not with the oligonucleotide alone. This
      inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA
      exhibits an anti-inflammatory property by interfering with the formation of the
      NF-kappaB-DNA complex in the nuclei through direct and redox-sensitive
      interactions and may play an important role in the prevention of inflammatory
      responses such as the atherosclerotic process.

PMID- 17027749
TI  - Adenosine A1 receptor antagonist versus montelukast on airway reactivity and
      inflammation.
AB  - Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans
      by activating adenosine A(1) receptors. Previously, it is reported that a high
      dose of L-97-1, a water-soluble, small molecule adenosine A(1) receptor
      antagonist, blocks early and late allergic responses, and bronchial hyper
      responsiveness to histamine in a hyper-responsive rabbit model of allergic
      asthma. Effects of a lower dose of L-97-1 are compared to montelukast, a
      cysteinyl leukotriene-1 receptor antagonist on early allergic response, late
      allergic response, bronchial hyper-responsiveness, and inflammatory cells in
      bronchoalveolar lavage (BAL) fluid following house dust mite administration.
      Rabbits received intraperitoneal injections of house dust mite extract within 24
      h of birth followed by booster house dust mite injections. Hyper-responsive
      rabbits received aerosolized house dust mite (2500 allergen units), 1 h after
      intragastric administration of L-97-1 (1 mg/kg) or montelukast (0.15 mg/kg) and
      lung dynamic compliance was measured for 6 h. Lung dynamic compliance was
      significantly higher following L-97-1 at all time points and with montelukast at
      60-300 min following house dust mite (P<0.05). L-97-1 blocks both early and late
      allergic responses. Montelukast blocks only the late allergic response. Both L-97
      1 and montelukast significantly blocked bronchial hyper-responsiveness at 24 h
      (P<0.05). Both L-97-1 and montelukast significantly reduced BAL eosinophils at 6
      h and neutrophils at 6 and 24 h (P<0.05). L-97-1 significantly reduced BAL
      lymphocytes at 6 and 24 h (P<0.05). Montelukast significantly reduced BAL
      macrophages at 6 and 24 h (P<0.05). By blocking both bronchoconstriction and
      airway inflammation, L-97-1 may be an effective oral anti-asthma treatment.

PMID- 17027750
TI  - Antidepressants enhance the antinociceptive effects of carbamazepine in the
      acetic acid-induced writhing test in mice.
AB  - Some antidepressants, as well as antiepileptics, are effective for treating pain
      of varying etiology. The present study was designed to characterize the
      antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a
      selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline
      reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic
      acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine
      (5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and
      significantly reduced the number of writhes induced by the injection of acetic
      acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than
      those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.)
      also showed a dose-dependent and significant antinociceptive effect. In
      combination studies, the co-administration of a sub-effective dose of
      carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.),
      fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.)
      significantly reduced the number of writhes. Additionally, the hole-board test
      revealed that the medications with significant antinociceptive effects barely
      produced changes in motor activity that could possibly affect writhing behavior.
      Thus, the present study demonstrated that the antinociceptive effect of
      carbamazepine is enhanced by combination with imipramine, fluvoxamine and
      milnacipran. Therefore, the combined therapy using antidepressants and
      carbamazepine may be useful clinically for the control of pain.

PMID- 17027751
TI  - Nicotine administration enhances conditioned inhibition in rats.
AB  - The effect of nicotine on conditioned inhibition was examined using a serial
      feature negative discrimination task. Nicotine (0.35 mg/kg) or vehicle was
      administered before each of the 16 training sessions. On some trials in each
      session, a tone was presented and followed by food reward. On other trials, the
      tone was preceded by a visual stimulus and not reinforced. Nicotine-treated rats
      exhibited greater discrimination between the two trial types as evidenced by less
      frequent responding during non-reinforced trials, and learned the discrimination
      in fewer sessions than vehicle-treated rats. In contrast, there were no group
      differences in responding during the reinforced trials.

PMID- 17027752
TI  - ZNF198, a zinc finger protein rearranged in myeloproliferative disease, localizes
      to the PML nuclear bodies and interacts with SUMO-1 and PML.
AB  - The ZNF198/FGFR1 fusion gene in atypical myeloproliferative disease produces a
      constitutively active cytoplasmic tyrosine kinase, unlike ZNF198 which is
      normally a nuclear protein. We have now shown that the ZNF198/FGFR1 fusion kinase
      interacts with the endogenous ZNF198 protein suggesting that the function of
      ZNF198 may be compromised in cells expressing it. Little is currently known about
      the endogenous function of ZNF198 and to investigate this further we performed a
      yeast two-hybrid analysis and identified SUMO-1 as a binding partner of ZNF198.
      These observations were confirmed using co-immunoprecipitation which demonstrated
      that ZNF198 is covalently modified by SUMO-1. Since many of the SUMO-1-modified
      proteins are targeted to the PML nuclear bodies we used confocal microscopy to
      show that SUMO-1, PML and ZNF198 colocalize to punctate structures, shown by
      immunocytochemistry to be PML bodies. Using co-immunoprecipitation we now show
      that PML and sumoylated ZNF198 can be found in a protein complex in the cell.
      Mutation of the SUMO-1 binding site in wild-type ZNF198 resulted in loss of
      distinct PML bodies, reduced PML levels and a more dispersed nuclear localization
      of the PML protein. In cells expressing ZNF198/FGFR1, which also lack the SUMO-1
      binding site, SUMO-1 is preferentially localized in the cytoplasm, which is
      associated with loss of distinct PML bodies. Recently, arsenic trioxide (ATO) was
      proposed as an alternative therapy for APL that was resistant to traditional
      therapy. Treatment of cells expressing ZNF198/FGFR1 with ATO demonstrated reduced
      autophosphorylation of the ZNF198/FGFR1 protein and induced apoptosis, which is
      not seen in cells expressing wild-type ZNF198. Overall our results suggest that
      the sumoylation of ZNF198 is important for PML body formation and that the
      abrogation of sumoylation of ZNF198 in ZNF198/FGFR1 expressing cells may be an
      important mechanism in cellular transformation.

PMID- 17027754
TI  - Effects of latanoprost on rodent intraocular pressure.
AB  - The aim of the present study was to evaluate the effects of the prostaglandin F2
      alpha analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes.
      Rodents have been increasingly used in glaucoma research; however, conflicting
      results regarding the actions of prostaglandins on rodent IOP have been
      published. In Wistar rats, a single dose of latanoprost (60 ng) produced a
      biphasic change in IOP: an initial rise in pressure (2.1+/-0.7 mmHg) peaking at 2
      h, followed by a prolonged hypotension with a peak reduction in IOP (5.2+/-0.7
      mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose
      related with ED50 values of 108 and 5.2 ng, respectively. These responses were
      antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6
      mice, a single dose of latanoprost also produced a biphasic response in IOP with
      an initial rise in pressure peaking between 1 and 2 h, followed by prolonged
      hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP
      response to topical latanoprost is characterized by an initial hypertension
      followed by a prolonged hypotension. This prolonged hypotension is similar to
      that measured in monkeys and humans. Taken together, these results support the
      idea that rodents can serve as in vivo models to study the actions of ocular
      hypotensive agents, such as prostaglandins.

PMID- 17027753
TI  - Epithelial-mesenchymal transition occurs after epidermal development in mouse
      skin.
AB  - In the present study, we studied epithelial-mesenchymal transition (EMT) with
      fetal and postnatal serial skin sections. E-cadherin, occludin and zonula
      occludens 1 (ZO-1)-expressing cells appear in the dermal area from E18.5 to
      postnatal day 9 (P9), with highest expression from P2 to P5. The co-expression of
      mesenchymal marker alpha-smooth muscle (alpha-SMA), fibronectin and vimentin with
      E-cadherin in these dermal cells was further examined. Almost no dermal cells
      express alpha-SMA before P0. From P2 to P6, cells expressing both E-cadherin and
      alpha-SMA appear in the dermis. In contrast, fibronectin-releasing cells were
      detected in the dermis as early as on E15.5, although on P5, some dermal cells
      was found weakly expressing both fibronectin and E-cadherin, most cells strongly
      expressing fibronectin did not express E-cadherin. Vimentin was mainly expressed
      in both endothelial and blood-derived cells and did not show co-expression with E
      cadherin. Confocal microscopy studies further found that during EMT, E-cadherin
      appears intracellularly, while the expression of alpha-SMA starts from the
      membrane area and moves to the cytosol of the cells. Our data are the first in
      vivo evidence that EMT occurs during mouse skin development. Dermal cells are
      derived from EMT and other origins, including blood, during skin development.

PMID- 17027755
TI  - Differential effects of water deprivation and rehydration on Fos and
      FosB/DeltaFosB staining in the rat brainstem.
AB  - This study examined the effects of dehydration and rehydration with water on Fos
      and FosB staining in the brainstem of rats. Male rats were water deprived for 48
      h (Dehyd, n=7) or 46 h followed by 2 h access to water (Rehyd, n=7). Controls had
      ad libitum access to water (Con, n=9). Brainstems were stained for Fos and
      FosB/DeltaFosB using commercially available antibodies. In the nucleus of the
      solitary tract (NTS), the number of Fos stained neurons was significantly
      increased by dehydration and increased further following rehydration (Con 5+/-1;
      Dehyd 22+/-1; Rehyd 48+/-5). The average number of Fos-positive cells in the
      parabrachial nucleus (PBN) was significantly increased only by rehydration (Con
      12+/-2; Dehyd 6+/-2; Rehyd 51+/-4). The area postrema (AP) showed significant
      increases in Fos staining after dehydration and rehydration (Fos: Con 4+/-1;
      Dehyd 28+/-3; Rehyd 24+/-3). In the rostral ventrolateral medulla (RVL), Fos
      staining significantly increased after dehydration and this effect was reduced by
      rehydration (Con 3+/-1; Dehyd 21+/-2; Rehyd 12+/-1). In contrast, Fos staining in
      the caudal ventrolateral medulla (CVL) was not significantly influenced following
      either dehydration or rehydration with water (Con 4+/-1; Dehyd 4+/-1; Rehyd 5+/
      1). FosB/DeltaFosB staining in the NTS, AP, and RVL was comparably increased by
      dehydration and rehydration. In the PBN and CVL, FosB/DeltaFosB staining was not
      affected by the treatments. Dehydration and rehydration have regionally specific
      effects on Fos and FosB/DeltaFosB staining in the brainstem.

PMID- 17027756
TI  - Transcriptional activation of the proapoptotic bik gene by E2F proteins in cancer
      cells.
AB  - BH3-only proteins are required for execution of apoptotic cell death. We have
      found that one of these proteins, Bik, is strongly induced in cancer cells
      treated with chemotherapeutic agents. Furthermore, we showed that chemotherapy
      induced expression of bik is independent of p53. Consistent with its pro
      apoptotic activity, blockade of bik expression reduces the adriamycin-mediated
      apoptotic cell death. We also found that the bik gene is transcriptionally
      activated by E2F proteins. Consistently, adriamycin induces the E2F-bik pathway.
      In addition, E2Fs transactivate bik by a p53-independent mechanism. Thus, our
      data indicate that transcriptional regulation of bik contributes to the efficient
      apoptotic response to chemotherapeutic agents.

PMID- 17027757
TI  - Regulation of Stat3 transcriptional activity by the conserved LPMSP motif for OSM
      and IL-6 signaling.
AB  - To achieve maximal transcriptional activity in response to gp130 cytokines,
      Serine-727 (Ser-727) of Stat3 is phosphorylated. Ser-727 resides in the LPMSP
      motif, the only conserved sequence among the transcription activation domains of
      several STATs. We show here that in addition to Ser-727, other residues in this
      LPMSP motif are also required for Stat3 activity in response to cytokine
      signaling through regulation of Ser-727 phosphorylation and recruitment of the
      transcription co-activator CBP/p300 to the promoters of Stat3-target genes for
      transcription activation. Hence, we have demonstrated a critical role for the
      whole conserved LPMSP motif in JAK-STAT signaling.

PMID- 17027758
TI  - Respective importance of protein folding and glycosylation in the thermal
      stability of recombinant feruloyl esterase A.
AB  - The thermal stability of four molecular forms (native, refolded, glycosylated,
      non-glycosylated) of feruloyl esterase A (FAEA) was studied. From the most to the
      least thermo-resistant, the four molecular species ranked as follows: (i)
      glycosylated form produced native, (ii) non-glycosylated form produced native,
      (iii) non-glycosylated form produced as inclusion bodies and refolded, and (iv)
      glycosylated form produced native chemically denatured and then refolded. On the
      basis of these results and of crystal structure data, we discuss the respective
      importance of protein folding and glycosylation in the thermal stability of
      recombinant FAEA.

PMID- 17027759
TI  - Counting abortions so that abortion counts: Indicators for monitoring the
      availability and use of abortion care services.
AB  - SUMMARY: Maternal mortality reduction has been a focus of major international
      initiatives for the past two decades. Widespread provision of emergency obstetric
      care (EmOC) has been shown to be an important strategy for addressing many of the
      complications that might otherwise lead to maternal death. However, unsafe
      abortion is one of the major causes of pregnancy-related deaths, and will be only
      partially addressed by EmOC. This manuscript presents a comprehensive approach to
      measuring whether abortion-related needs are met. PROPOSED METHODS: We propose a
      set of indicators for monitoring the implementation of safe abortion care (SAC)
      interventions. We build on the model developed for monitoring the availability
      and use of Emergency Obstetric (EmOC) services. We describe the critical elements
      ("signal functions") of SAC - including treatment of abortion complications,
      legal, induced abortion and postabortion contraception - and define the
      indicators necessary to assess the availability, utilization and quality of
      abortion-related services. SAMPLE EVIDENCE: Data from 5 countries suggest there
      are sufficient service delivery points to provide decentralized abortion care,
      but that the full range of necessary abortion care services may not be provided
      at all these sites. Studies from several countries also show that many women
      receiving services for the treatment of abortion complications accept
      contraceptive methods when offered prior to discharge. This is an important
      strategy for reducing unwanted pregnancy, repeat unsafe abortion and risk for
      abortion-related mortality. Both findings suggest there are considerable
      opportunities within the present facilities to improve the delivery of abortion
      care services. CONCLUSION: This article recommends that the proposed model
      undergo field-testing on its own or in conjunction with the EmOC indicators, and
      encourages increased support for this important but often neglected aspect of
      pregnancy-related health.

PMID- 17027760
TI  - Characterization of a Trypanosoma cruzi antigen with homology to intracellular
      mammalian lectins.
AB  - Two cDNAs, isolated from a Trypanosoma cruzi amastigote library immunoscreened
      with sera from patients with Chagas disease, encode proteins with sequence
      homology to eukaryotic components of the cellular sorting and recycling
      machinery. These proteins, denominated TcAGL, present an N-terminal lectin domain
      and a C-terminal region containing repetitive amino acids and a poly-glutamine
      tract. They are products of polymorphic alleles of a single copy gene
      constitutively expressed during the parasite life cycle. Polyclonal antibodies
      obtained from mice immunized with the recombinant antigen recognize proteins with
      apparent molecular weight ranging from 95 to 120 kDa in cell lysates from all
      three life stages and in various strains of the parasite. Sera from Chagas
      disease patients recognize the recombinant antigen in ELISA and
      immunoprecipitation assays but not in Western blot assays under denaturing
      conditions. Consistent with its proposed role in the glycoprotein secreting
      pathway, immunofluorescence analyses and expression of a green fluorescent
      protein-tagged TcAGL protein indicate a sub-cellular localization in the vicinity
      of the flagellar pocket membrane and the Golgi complex of the parasite.

PMID- 17027761
TI  - Independent component model of the default-mode brain function: Assessing the
      impact of active thinking.
AB  - The "default-mode" network is an ensemble of cortical regions, which are
      typically deactivated during demanding cognitive tasks in functional magnetic
      resonance imaging (fMRI) studies. Using functional connectivity, this network can
      be conceptualized and studied as a "stand-alone" function or system. Regardless
      of the task, independent component analysis (ICA) produces a picture of the
      "default-mode" function even when the subject is performing a simple sensori
      motor task or just resting in the scanner. This has boosted the use of default
      mode fMRI for non-invasive research in brain disorders. Here, we studied the
      effect of cognitive load modulation of fMRI responses on the ICA-based pictures
      of the default-mode function. In a standard graded working memory study based on
      the n-back task, we used group-level ICA to explore the variability of the
      default-mode network related to the engagement in the task, in 10 healthy
      volunteers. The analysis of the default-mode components highlighted similarities
      and differences in the layout under three different cognitive loads. We found a
      load-related general increase of deactivation in the cortical network.
      Nonetheless, a variable recruitment of the cingulate regions was evident, with
      greater extension of the anterior and lesser extension of the posterior clusters
      when switching from lower to higher working memory loads. A co-activation of the
      hippocampus was only found under no working memory load. As a generalization of
      our results, the variability of the default-mode pattern may link the default
      mode system as a whole to cognition and may more directly support use of the ICA
      model for evaluating cognitive decline in brain disorders.

PMID- 17027762
TI  - Light-induced Fos expression in the suprachiasmatic nucleus of the four-striped
      field mouse, Rhabdomys pumilio: A southern African diurnal rodent.
AB  - Previous studies have suggested that nocturnal and diurnal species of rodents
      differ in their circadian responses to light including phase shifts and early
      gene expression. Rhabdomys pumilio, the four-striped field mouse, is diurnal both
      in nature and in the laboratory. We studied in this species the response of the
      suprachiasmatic nucleus (SCN) to light stimuli at different time periods using
      light-induced expression of Fos as marker of neuronal activity. Fos induction in
      the SCN was investigated using immunohistochemistry and quantitative image
      analysis. The animals were exposed to a 15 min light pulse with monochromatic
      green light at different circadian times throughout a 24-h cycle. Animals
      maintained in constant darkness served as controls. R. pumilio exhibited an
      endogenous Fos rhythm in the SCN during constant darkness with highest expression
      during the subjective day at circadian time (CT) 2 and CT10. Photic stimulation
      resulted in significant Fos induction in the SCN at CT6, CT14, CT18 and CT22,
      compared to controls kept in constant darkness, with a peak of expression at
      CT22, i.e. during late subjective night, mainly due to expression in the ventral
      SCN. In tract tracing experiments based on the use of cholera toxin subunit B, we
      found that retinal fibres innervate mainly the contralateral ventral SCN. The
      intergeniculate leaflet received bilateral retinal innervation with overlap
      between ipsilateral and contralateral fibres. Altogether the data show that the
      rodent R. pumilio is a unique diurnal model for chronobiological studies.

PMID- 17027763
TI  - Glutamatergic innervation of growth hormone-releasing hormone-containing neurons
      in the hypothalamic arcuate nucleus and somatostatin-containing neurons in the
      anterior periventricular nucleus of the rat.
AB  - Growth hormone-releasing hormone (GHRH) and somatostatin are the two main
      hypothalamic neurohormones, which stimulate or inhibit directly hypophysial
      growth hormone (GH) release. Majority of the GHRH neurons projecting to the
      median eminence is situated in the arcuate nucleus and the somatostatin neurons
      in the anterior periventricular nucleus. Data suggest that the excitatory amino
      acid glutamate may play an important role in the control of hypothalamic
      neuroendocrine neurons and processes including the control of GH. There is a
      dense plexus of glutamatergic fibres in the hypothalamic arcuate and anterior
      periventricular nucleus. The aim of the present studies was to examine the
      relationship of these fibres to the GHRH neurons in the arcuate nucleus and to
      somatostatin neurons in the anterior periventricular nucleus. Double-labelling
      immuno-electron microscopy was used. Glutamatergic structures were identified by
      the presence of vesicular glutamate transporter 2 (VGluT2) (a selective marker of
      glutamatergic elements) immunoreactivity. A significant number of VGluT2
      immunoreactive boutons was observed to make asymmetric type of synapses with GHRH
      immunostained nerve cells in the arcuate and with somatostatin neurons in the
      anterior periventricular nucleus. A subpopulation of somatostatin-immunoreactive
      neurons displayed also VGluT2 immunoreactivity. Our findings provide direct
      neuromorphological evidence for the view that the action of glutamate on GH
      release is exerted, at least partly, directly on GHRH and somatostatin neurons
      releasing these neurohormones into the hypophysial portal blood.

PMID- 17027764
TI  - Temporal dynamics of face repetition suppression.
AB  - Single-unit recordings and functional brain imaging studies have shown reduced
      neural responses to repeated stimuli in the visual cortex. Using MEG, we compared
      responses evoked by repetitions of neutral faces to those evoked by fearful
      faces, which were either task relevant (targets) or irrelevant (distracters).
      Faces evoked a bi-phasic response in extrastriate cortex, peaking at 160-185 ms
      and at 220-250 ms, with stronger responses to neutral faces at the earlier
      interval and stronger responses to fearful faces at the later interval. At both
      latencies, repetitions of neutral and fearful targets resulted in reduced
      amplitude of the MEG signal. Additionally, we found that the context in which
      targets were presented affected their processing: fearful distracters increased
      the responses evoked by both neutral and fearful targets. Our data indicate that
      valence enhancement and context effects can be detected in extrastriate visual
      cortex within 250 ms and that these processes likely reflect feedback from other
      regions.

PMID- 17027765
TI  - Relative expression of D3 dopamine receptor and alternative splice variant D3nf
      mRNA in high and low responders to novelty.
AB  - Studies in rodents suggest an important role for the D3 dopamine receptor in
      regulating locomotor responses to spatial novelty and psychostimulants. The D3
      receptor alternatively spliced variant D3nf produces a non-dopamine binding
      protein that may alter D3 receptor localization by dimerizing with the full
      length receptor. In the high responder/low responder (HR/LR) model, the locomotor
      response to an inescapable, novel spatial environment predicts individual
      differences in the locomotor and rewarding effects of psychostimulants. We
      hypothesized that individual differences in D3 receptor expression could
      contribute to individual differences in the locomotor response to novelty in the
      HR/LR model. To test this hypothesis, we screened rats for response to a novel
      spatial environment and analyzed brain tissue for mRNA levels of the D3 receptor
      and D3nf by real-time RT-PCR. The ratios of D3/D3nf mRNA in prefrontal cortex and
      substantia nigra/ventral tegmentum were significantly lower in HRs than in LRs.
      There were no differences in relative expression of D3/D3nf between HRs and LRs
      in nucleus accumbens. These data further support a role for the D3 dopamine
      receptor in behavioral responses to novelty and, given the established
      relationship between novelty and psychostimulant responses, suggest that the D3
      receptor may be an important target for assessment of drug abuse vulnerability.
      Additionally, these findings are consistent with the hypothesis that alternative
      splicing may contribute to regulation of D3 dopamine receptor function.

PMID- 17027766
TI  - Blood content modulates the induction of heat shock proteins in the neurovascular
      network.
AB  - Heat shock proteins are ubiquitous members of a family of molecular chaperones
      that protect various cell populations from injury. Up-regulation of heat shock
      proteins, particularly the 70 kDa species, bind selectively to denatured or
      partially damaged polypeptides that would otherwise perturb cell function and
      initiate cell death programs. In this regard, induction of heat shock proteins
      provides protection from cerebral ischemia in animal models of stroke.
      Endothelial cells, in particular, are intimately involved in the above protective
      event as these cells mount a stress response with induction of the 70 kDa heat
      shock protein. However, the coupling of heat shock proteins and the neurovascular
      response are not yet known. Here we show that blood content is an important
      factor in this stress response as rats devoid of blood content do not display a
      heat shock response in the microvasculature of the hippocampal formation. This
      lack of stress response, however, is reversed when rats are reperfused with
      exogenous rat or human blood content. We propose a new ischemic-sensing role for
      blood that serves to integrate information about protein-damaging conditions and
      heat shock protein levels in the neurovascular network. Further characterization
      of this sensing role could represent an attractive new approach to treatment of
      global ischemia and other microvascular pathologies.

PMID- 17027767
TI  - Negative symptoms: A review of schizophrenia, melancholic depression and
      Parkinson's disease.
AB  - Negative symptoms generally refer to a reduction in normal functioning. In
      schizophrenia they encompass apathy, anhedonia, flat affect, avolition, social
      withdrawal and, on some accounts, psychomotor retardation. Negative symptoms have
      been identified in other psychiatric disorders, including melancholic depression,
      and also in neurological disorders, such Parkinson's disease. Achieving a better
      understanding of negative symptoms constitutes a priority in mental health.
      Primarily, negative symptoms represent an unrelenting, intractable and disabling
      feature for patients, often amounting to a severe burden on families, carers and
      the patients themselves. Identifying and understanding subgroups within disorders
      may also contribute to the clinical care and scientific understanding of the
      pathophysiology of these disorders. The purpose of this paper is to review the
      current literature on negative symptoms in schizophrenia and explore the idea
      that negative symptoms may play an important role not only in other psychiatric
      disorders such as melancholic depression, but also in neurological disorders,
      such as Parkinson's disease. In each disorder negative symptoms manifest with
      similar motor and cognitive impairments and are associated with comparable
      neuropathological and biochemical findings, possibly reflecting analogous
      impairments in the functioning of frontostriatal-limbic circuits.

PMID- 17027768
TI  - The prefrontal cortex in the Gottingen minipig brain defined by neural projection
      criteria and cytoarchitecture.
AB  - In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig
      brain the distribution of reciprocal thalamocortical projections was investigated
      using anterograde and retrograde tracing techniques and evaluated in relation to
      the specific cytoarchitectonic organization. Tracers were visualized using
      standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an
      MRI paramagnetic tracer. The in vivo tract tracing turned out to be very
      sensitive with a high correspondence to the histological labelling. Tracers
      injected into the mediodorsal thalamus labelled the medial and rostral pole of
      the frontal lobe as well as the anterior cingulate, anterior insular and
      dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of
      these connections were tested from injections into the traced frontal cortices
      indicating that the PFC has cortical connections to different parts of the MD
      nucleus. Although the granular layer IV, characteristic of primate PFC could not
      be identified, both cytoarchitectonic and connectional data suggests that the
      Gottingen minipig has a structurally divided prefrontal cortex. Stereological
      estimates of PFC volume showed that the Gottingen minipig PFC constitutes about
      24% of the total neocortex volume and 10% of the total brain volume.

PMID- 17027769
TI  - Differential effects of age on sequence learning and sensorimotor adaptation.
AB  - Although many studies have documented declines in the ability of the elderly to
      learn new manual motor skills, studies have not directly compared the capacity of
      older adults to learn sequences versus adapt to sensorimotor perturbations within
      the context of the same task paradigm, despite differences in the underlying
      neural mechanisms and strategic processes supporting the two types of learning.
      The purpose of the current study was to exploit these task differences in an
      effort to determine whether aging results in a generalized or more specific skill
      learning deficit. Groups of young and older adult subjects learned to make a
      sequence of actions, adapted to one of two visuomotor rotations, or adapted to an
      altered gain of display, all while performing the same basic manual joystick
      aiming task. While the older adults exhibited normal sequence learning in
      comparison to the young adults, they exhibited impairments in all three of the
      adaptation tasks. These deficits in adaptation for the older adults were
      associated with hypometric movements and reduced velocity modulation in
      comparison to that seen in the younger adults. These data suggest that older
      adults may have greater difficulty with learning cerebellar-mediated motor
      skills.

PMID- 17027770
TI  - NMDA receptor activity in learning spatial procedural strategies I. The influence
      of hippocampal lesions.
AB  - To acquire knowledge about the environment two types of learning are necessary:
      declarative localizatory learning about where environmental cues and the subject
      are, and procedural learning about how to explore and move around the
      environment. Experimental data indicate that hippocampal regions are involved in
      spatial learning, playing a key role in building spatial cognitive maps. The
      contribution of hippocampal NMDA receptors to spatial functions is indicated by
      the disruption of place learning when NMDA long-term potentiation is blocked.
      Conversely, the hippocampal contribution to the acquisition of procedural
      strategies is still controversial. Inactivation of the hippocampus by
      antagonizing the activity of AMPA/kainate receptors results in impaired spatial
      procedural learning. However, in the presence of a blockade of NMDA long-term
      potentiation in hippocampal areas it is still possible to learn explorative
      strategies. To investigate the involvement of the hippocampal NMDA receptors in
      spatial procedural learning, an NMDA receptor antagonist (CGS 19755) was
      administered i.p. to unlesioned animals or to animals with total ablation of
      hippocampal structures that had been tested in the Morris water maze. The CGS
      administration induced peripheral circling in both unlesioned control animals and
      in rats with bilateral hippocampal ablation. Conversely, circling was not
      observed if the drug-treated animals (either unlesioned or lesioned) had been
      spatially trained before drug administration. These findings indicate that even
      in the absence of the hippocampal formation the NMDA receptor antagonist found a
      site of action to influence the acquisition of spatial procedures to search for
      the platform.

PMID- 17027771
TI  - NMDA receptor activity in learning spatial procedural strategies II. The
      influence of cerebellar lesions.
AB  - Experimental data support the involvement of cerebellar circuits in the
      acquisition of spatial procedural competences. Since the ability to acquire new
      procedural competences is lost when cerebellar regions are lesioned or when NMDA
      receptor activity is blocked, we analyzed whether the learning of explorative
      strategies is affected by blocking NMDA receptor activity in the presence of
      cerebellar lesions. To this aim, the NMDA receptor antagonist (CGS 19755, 7
      mg/kg) was administered i.p. to un-lesioned rats, or rats subjected to total
      ablation of the cerebellum or to hemi-cerebellectomy. CGS 19755 and
      cerebellectomy both produced water maze behavior characterized by circling.
      Administration of CGS 19755 did not modify the Morris Water Maze (MWM) peripheral
      circling behavior of cerebellectomized animals. Circling was the dominant
      strategy of hemicerebellectomized animals in the absence of drugs. However,
      increasingly compulsive circling was observed under the action of CGS 19755.
      Circling was not observed if the drug-treated animals (un-lesioned or lesioned)
      had been previously trained. In conclusion, the NMDA antagonist caused severe
      impairment in the acquisition of spatial procedures, thus mimicking the
      consequences of cerebellar ablation on spatial procedural learning. Based on the
      present findings, we hypothesize that cerebellar NMDA receptor activity is
      involved in the acquisition of procedural spatial competence.

PMID- 17027772
TI  - Acute effects of moclobemide and deprenyl on 5-HT synthesis rates in the rat
      brain: An autoradiographic study.
AB  - Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) released from nerve
      terminals in the brain are primarily removed from the synaptic cleft by a
      reuptake mechanism. In part, the homeostasis is maintained by monoamine oxidase
      (MAO) deamination achieved primarily intracellularly. The present study's aim was
      to examine the effect of the acute administration of the MAO inhibitors,
      moclobemide (a MAO-A inhibitor) and deprenyl (a MAO-B inhibitor), on 5-HT
      synthesis rates, measured in discrete regions of the rat brain by an
      autoradiographic method, using alpha-[14C]methyl-l-tryptophan as a tracer. MAO
      inhibitors have different effects on 5-HT synthesis rates in the cell bodies and
      areas of the nerve terminals. Moclobemide (10 mg/kg, i.p. 30 min before the
      tracer injection) and deprenyl (3 mg/kg, i.p. 2 h before the tracer injection)
      decreased the 5-HT synthesis rates in the dorsal (-18% and -22%) and median (-22%
      and -33%) raphe, respectively. Moclobemide also significantly decreased 5-HT
      synthesis in the entire nerve terminal areas investigated. The reductions were
      between 23% (cingulate cortex) and 50% (locus coeruleus). Deprenyl did not
      significantly affect 5-HT synthesis in the nerve terminals. The present results
      suggest that MAO-A, and to a lesser extent, MAO-B, are involved in the regulation
      of 5-HT synthesis in the rat brain. The mechanism(s) of MAO inhibitors' action on
      5-HT synthesis in the raphe nuclei are probably related to an increase in the
      extraneuronal 5-HT concentration and also to the interaction between the
      serotonergic and catecholaminergic neurons. The reduction of 5-HT synthesis in
      the raphe nuclei likely occurs by an action of extracellular 5-HT via the
      dendritic autoreceptors with a possible contribution from the action of
      extracellular DA and NE. In the terminal regions, the most likely mechanism is
      via the presynaptic autoreceptors through which elevated extraneuronal 5-HT acts
      on synthesis control. However, there is also a possibility that the elevation in
      intraneuronal 5-HT directly inhibits its synthesis, especially following deprenyl
      treatment. A great influence of moclobemide on 5-HT synthesis could be related to
      its antidepressant action.

PMID- 17027773
TI  - Peripheral mGluR5 antagonist attenuated craniofacial muscle pain and inflammation
      but not mGluR1 antagonist in lightly anesthetized rats.
AB  - The present study investigated the role of peripheral group I metabotropic
      glutamate receptors (mGluRs) in MO-induced nociceptive behaviour and inflammation
      in the masseter muscles of lightly anesthetized rats. Experiments were carried
      out on male Sprague-Dawley rats weighing 300-400 g. After initial anesthesia with
      sodium pentobarbital (40 mg/kg, i.p.), one femoral vein was cannulated and
      connected to an infusion pump for intravenous infusion of sodium pentobarbital.
      The rate of infusion was adjusted to provide a constant level of anesthesia.
      Mustard oil (MO, 30 microl) was injected into the mid-region of the left masseter
      muscle via a 30-gauge needle over 10s. After 30 microl injection of 5, 10, 15, or
      20% MO into the masseter muscle, the total number of hindpaw shaking behaviour
      and extravasated Evans' blue dye concentration in the masseter muscle were
      significantly higher in the MO-treated group in a dose-dependent manner compared
      with the vehicle (mineral oil)-treated group. Intramuscular pretreatment with 3
      or 5% lidocaine reduced MO-induced hindpaw shaking behaviour and increases in
      extravasated Evans' blue dye concentration. Intramuscular pretreatment with 5 mM
      MCPG, non-selective group I/II mGluR antagonist, or MPEP, a selective group I
      mGluR5 antagonist, produced a significant attenuation of MO-induced hindpaw
      shaking behaviour and increases in extravasated Evans' blue dye concentration in
      the masseter muscle while LY367385, a selective group I mGluR1 antagonist, did
      not affect MO-induced nociceptive behaviour and inflammation in the masseter
      muscle. These results indicate that peripheral mGluR5 plays important role in
      mediating MO-induced nociceptive behaviour and inflammation in the craniofacial
      muscle.

PMID- 17027774
TI  - Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder.
AB  - INTRODUCTION: REM sleep behavior disorder (RBD) is a parasomnia characterized by
      a loss of atonia and an increased phasic muscle activity during REM sleep.
      Idiopathic RBD frequently herald an alpha-synucleinopathy, including such as
      Parkinson's disease (PD) and dementia with Lewy Body (DLB). Pathological changes
      in the anterior olfactory nucleus and olfactory loss occur very early in the
      course of PD and DLB. The aim of the study was to assess olfactory function in a
      large group of idiopathic RBD patients. METHODS: Fifty-four consecutive
      polysomnographically-confirmed iRBD patients (44 men, 10 women; mean age: 69.2+/
      8.3 years; mean Unified Parkinson's Disease Rating Scale Part III (UPDRS-III)
      score: 4.9+/-4.3) and 54 age and gender-matched control subjects underwent the
      Brief University of Pennsylvania Smell Identification Test (B-SIT). RESULTS: A
      marked olfactory impairment was observed in the RBD group (mean B-SIT score:
      7.1+/-2.5 versus 9.4+/-1.8; p < 0.0001), with 33 (61.1%) RBD patients versus 9
      (16.6%) controls showing abnormal olfactory function (p < 0.0001). No correlation
      was found between the degree of olfactory loss and either duration of RBD
      symptoms or UPDRS-III score. Deficit in recognize paint thinner odorant showed
      the highest positive predictive value (0.95) for identifying idiopathic RBD.
      CONCLUSIONS: The olfactory deficit found in most idiopathic RBD patients shares
      similarities with that described in PD and may be a sign of a widespread
      neurodegenerative process. Its detection may help in identifying subjects at
      higher risk of developing an alpha-synucleinopathy-mediated neurodegeneration.

PMID- 17027775
TI  - Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel
      Prize award to Santiago Ramon y Cajal.
AB  - Exactly 100 years ago, the Nobel Prize for Physiology and Medicine was awarded to
      Santiago Ramon y Cajal, "in recognition of his meritorious work on the structure
      of the nervous system". Cajal's great contribution to the history of science is
      undoubtedly the postulate of neuron theory. The present work makes a historical
      analysis of the circumstances in which Cajal formulated his theory, considering
      the authors and works that influenced his postulate, the difficulties he
      encountered for its dissemination, and the way it finally became established. At
      the time when Cajal began his neurohistological studies, in 1887, Gerlach's
      reticular theory (a diffuse protoplasmic network of the grey matter of the nerve
      centres), also defended by Golgi, prevailed among the scientific community. In
      the first issue of the Revista Trimestral de Histologia Normal y Patologica (May,
      1888), Cajal presented the definitive evidence underpinning neuron theory, thanks
      to staining of the axon of the small, star-shaped cells of the molecular layer of
      the cerebellum of birds, whose collaterals end up surrounding the Purkinje cell
      bodies, in the form of baskets or nests. He thus demonstrated once and for all
      that the relationship between nerve cells was not one of continuity, but rather
      of contiguity. Neuron theory is one of the principal scientific conquests of the
      20th century, and which has withstood, with scarcely any modifications, the
      passage of more than a 100 years, being reaffirmed by new technologies, as the
      electron microscopy. Today, no neuroscientific discipline could be understood
      without recourse to the concept of neuronal individuality and nervous
      transmission at a synaptic level, as basic units of the nervous system.

PMID- 17027776
TI  - Nitric oxide synthase in retina and optic nerve head of rat with increased
      intraocular pressure and effect of timolol.
AB  - We investigated the expression of nitric oxide synthase (NOS) isoforms -1, -2 and
      -3 in the retina and optic nerve head (ONH) in an experimental rat model of
      elevated intraocular pressure (IOP) before and after treatment with timolol, to
      assess whether its neuroprotective action is associated with the activity of
      these enzymes. Episcleral vein cauterization in unilateral eyes of Wistar rats
      was performed to produce elevated IOP. Histological sections of retina and ONH
      from animals with normal IOP, with elevated IOP, and elevated IOP treated with
      timolol, were studied by immunohistochemistry with antibodies to NOS-1, NOS-2,
      and NOS-3. In the control rats, NOS-1 was localized to photoreceptor inner
      segments, amacrine cells and bipolar cells in the retina, and in astrocytes,
      pericytes and vascular nitrergic terminals in the ONH. NOS-3 immunostaining
      localized to the endothelial cells. The rats with elevated IOP showed increased
      expression of NOS-1 in the plexiform layers of the retina and reactive astrocytes
      in the ONH. These cells also showed NOS-2 positivity. The rats treated with
      timolol showed reduced expression of NOS-1 in the retina and ONH. NOS-2 was only
      detected in a few groups of astrocytes in the ONH. NOS-3 was unchanged in both
      elevated IOP and timolol-treated groups. These results show that excessive levels
      of NO synthesized by the NOS-1 and -2 isoforms, considered neurotoxic, might
      contribute to the progressive lesions of retinal ganglion cell axons. Their
      reduction after treatment suggests a possible neuroprotective effect of timolol
      in neurons exposed to excessive amounts of NO.

PMID- 17027777
TI  - Antidepressant treatment reduces Fos-like immunoreactivity induced by swim stress
      in different columns of the periaqueductal gray matter.
AB  - Antidepressant treatment attenuates behavioral changes induced by uncontrollable
      stress. The periaqueductal gray matter (PAG) is proposed to be a brain site
      involved in the behavioral responses to uncontrollable stress and antidepressant
      effects. The main goal of the present study was to investigate the effect of
      antidepressant treatment on the pattern of neural activation of the PAG along its
      mediolateral and rostrocaudal subregions after a forced swim stress episode. Male
      Wistar rats were sub-acutely treated with desipramine (a selective noradrenaline
      re-uptake blocker, three injections of 10 mg/kg in 24 h) or clomipramine (a non
      selective serotonin and noradrenaline re-uptake blocker, three injections of 10
      mg/kg in 24 h) and submitted to the forced swimming test (FST). Two hours after
      the test their brain were removed for Fos immunohistochemistry. Fos-like
      immunoreactivity (FLI) in rostral, intermediate and caudal portions of
      dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral
      (vlPAG) PAG were quantified by a computerized system. The FST session increased
      FLI in most parts of the PAG. Previous treatment with desipramine or clomipramine
      reduced FLI in all columns of the PAG. FLI in the PAG correlated positively with
      to the immobility time and negatively with to climbing behavior scored during the
      test. These results indicate that neurons in the PAG are activated by
      uncontrollable stress. Moreover, inhibitory action of antidepressants on this
      activity may be associated with the anti-immobility effects of these drugs in the
      FST.

PMID- 17027778
TI  - Acute methylphenidate treatments reduce sucrose intake in restricted-fed bingeing
      rats.
AB  - Recent evidence suggests that methylphenidate HCl may be effective at limiting
      the frequency and the amount of binge eating. The present study investigated if
      daily treatments with methylphenidate reduced the bingeing-like behavior observed
      in restricted-fed adult male rats. Three groups (n = 6) received peripheral
      injections of methylphenidate in doses of 1.5 or 0.75 mg/kg/day, or saline, 3
      days prior and 7 days during a previously characterized intermittent feeding
      regimen that results in a gradual increase of sucrose and food intake. The
      higher, but not the lower, dose of methylphenidate reduced sucrose intake to an
      asymptotic level starting after 3 days of the feeding protocol and concurrently
      led to an increase in the intake of chow. The high dose methylphenidate group
      also had two-fold lower plasma insulin levels compared with the saline-treated
      animals at the time of sacrifice on the last day of the feeding regimen. Further
      histological assays revealed that the methylphenidate treatments, irrespective of
      the dose used, resulted in selectively higher dopamine transporter and D2-like
      receptor labeled bindings in the shell region of the nucleus accumbens. These
      results suggest that relatively low-dose methylphenidate treatments may be
      effective for the management of binge eating by reducing the intake of palatable
      foods and may not interfere with short-term regulation of energy balance. These
      findings further support the notion that the mesoaccumbens dopamine system plays
      an important role in restricted access-induced sucrose bingeing in this rat
      model.

PMID- 17027779
TI  - Perceptual contributions to problem solving: Chunk decomposition of Chinese
      characters.
AB  - Chunk decomposition is the decomposing of familiar patterns into their component
      elements so that they can be regrouped in another meaningful manner. Such a
      regrouping is sometimes critically required in problem solving because during
      initial encoding the problem elements become automatically grouped into familiar
      chunks and this may prohibit finding a novel or efficient solution to problems
      [G. Knoblich, S. Ohlsson, H. Haider, D. Rhenius, Constraint relaxation and chunk
      decomposition in insight problem solving, J. Exp. Psychol. Learn. Mem. Cogn. 25
      (1999) 1534-1556]. In order to elucidate the brain mechanisms underlying the
      process of chunk decomposition, we developed a task that uses Chinese character
      as materials. Chinese characters are ideal examples of perceptual chunks. They
      are composed of radicals, which in turn, are composed of strokes. Because
      radicals are meaningful chunks themselves but strokes are not meaningful in
      isolation, it is much easier to separate a character by its radicals than to
      separate a character by its strokes. By comparing the stroke-level decomposition
      and the radical-level decomposition, we observed activities in occipital,
      frontal, and parietal lobes. Most importantly, during the moment of chunk
      decomposition, we found the early visual cortex showed a tendency of negative
      activation whereas the higher visual cortex showed a tendency of positive
      activation. This suggests that in order to successfully decompose a chunk, the
      higher visual areas must at least partly be 'disconnected' from the input
      provided by early visual processing in order to allow simple features to be
      rearranged into a different perceptual chunk. We conclude that early perceptual
      processes can crucially affect thinking and problem solving.

PMID- 17027780
TI  - Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol
      induced impairment of long-term potentiation in rat hippocampal slices.
AB  - Enhancing inhibition via gamma-aminobutyric acid type A (GABA(A)) receptors
      contributes to anesthetic-induced impairment of long-term potentiation (LTP) of
      excitatory synaptic transmission, which may account for general anesthesia
      associated memory impairment (amnesia). The neuron-specific K+ -Cl- cotransporter
      2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low
      intracellular chloride concentration required for the hyperpolarizing actions of
      GABA via GABA(A) receptors. To explore a possible role of KCC2-dependent
      inhibition in anesthetic-induced impairment of LTP, we used field excitatory
      postsynaptic potentials (fEPSP) recording and immunoblotting to study the effect
      of propofol on LTP maintenance and KCC2 expression in CA1 region of rat
      hippocampal slices. We found that propofol (30 microM) not only impaired LTP
      expression but also prevented LTP-accompanied downregulation of KCC2 without
      affecting the basal transmission of glutamatergic synapses. Moreover, the
      recurrent inhibition in hippocampal slices was enhanced by propofol. These
      propofol-induced effects were completely abolished by picrotoxin, a specific
      GABA(A) receptor-chloride channel blocker. Thus, enhancement of GABAergic
      inhibition and suppression of neuronal excitability may account for the sustained
      expression of KCC2 and the impairment of LTP by propofol. Together, this study
      supports a novel role for KCC2 in LTP expression and gives hints to a molecular
      mechanism, by which anesthetics might cause impairment of LTP.

PMID- 17027781
TI  - Respiratory drive in hindlimb motoneurones of the anaesthetized female cat.
AB  - Anatomical studies have shown a monosynaptic projection from nucleus
      retroambiguus (NRA) to semimembranosus (Sm) motor nucleus in female cats, which
      is stronger in oestrus. Expiratory bulbospinal neurones are the best documented
      functional cell type in the NRA. If these cells participate in this projection,
      an expiratory drive would be expected in Sm motoneurones and this drive would be
      expected to be stronger in oestrus. In anaesthetized, paralyzed,
      ovariohysterectomized female cats, artificially ventilated to produce a strong
      respiratory drive (as monitored by phrenic nerve discharges), intracellular
      recordings were made from Sm motoneurones and from motoneurones in the
      surrounding hindlimb motor nuclei that are outside the focus of the NRA
      projection. The animals comprised two groups: either treated for 7 days with
      oestradiol benzoate (oestrous) or untreated (non-oestrous). Central respiratory
      drive potentials (CRDPs) were observed in most motoneurones of both groups, with
      amplitudes larger for the oestrous than for the non-oestrous group (1.58+/-1.34
      mV versus 0.89+/-0.79 mV, mean+/-S.D.). However, the CRDPs most often consisted
      of a maximum depolarization in early expiration, which declined in late
      expiration and into inspiration. This pattern is different from the incrementing
      firing pattern of most expiratory bulbospinal neurones. The CRDPs in Sm and
      semitendinosus motoneurones (located in the same motor column) were of similar
      size and frequency to CRDPs in motoneurones outside that column. The hypothesis
      that expiratory bulbospinal neurones are significantly involved in the projection
      was rejected. Alternative sources and possible functional roles for the CRDPs are
      discussed.

PMID- 17027782
TI  - Induction of dopaminergic neurons from growth factor expanded neural
      stem/progenitor cell cultures derived from human first trimester forebrain.
AB  - Multipotent stem/progenitor cells derived from human first trimester forebrain
      can be expanded as free-floating aggregates, so called neurospheres. These cells
      can differentiate into neurons, astrocytes and oligodendrocytes. In vitro
      differentiation protocols normally yield gamma-aminobutyric acid-immunoreactive
      neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found.
      The present report describes conditions under which 4-10% of the cells in the
      culture become TH immunoreactive (ir) neurons within 24h. Factors including
      acidic fibroblast growth factor (aFGF) in combination with agents that increase
      intracellular cyclic AMP and activate protein kinase C, in addition to a
      substrate that promotes neuronal differentiation appear critical for efficient TH
      induction. The cells remain THir after trypsinization and replating, even when
      their subsequent culturing takes place in the absence of inducing factors.
      Consistent with a dopaminergic phenotype, mRNAs encoding aromatic acid
      decarboxylase, but not dopamine-beta-hydroxylase were detected by quantitative
      real time RT-PCR. Ten weeks after the cells had been grafted into the striatum of
      adult rats with unilateral nigrostriatal lesions, only very few of the surviving
      human neurons expressed TH. Our data suggest that a significant proportion of
      expandable human neural progenitors can differentiate into TH-expressing cells in
      vitro and that they could be useful for drug and gene discovery. Additional
      experiments, however, are required to improve the survival and phenotypic
      stability of these cells before they can be considered useful for cell
      replacement therapy in Parkinson's disease.

PMID- 17027783
TI  - Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to
      autobiographic test items.
AB  - The purpose of this experiment was to assess the effects of probe familiarity,
      the consequences of having recently retrieved an autobiographic memory (AM), on
      subsequent recall. This was accomplished by replicating an earlier imaging
      experiment, using the same participants and memory probes. Subtractions between
      sessions showed significant pre-exposure effects (i.e., drop in BOLD signal
      intensity) in the prefrontal cortex, thalamus, cerebellum and other brain
      structures. Further, region of interest (ROI) analysis illustrated a significant
      decrease in neural activity in the hippocampus in both conditions. The results
      are discussed in terms of the pre-scan interview technique, a method applied in
      AM research to procure personal information. Although invaluable, we emphasize it
      must be used with caution as it can result in a loss of power. The widespread use
      of this method in AM research may explain why studies often fail to find evidence
      of significant responding in the hippocampus in response to memory probes.
      Alternatively, when activity in the hippocampus is reported, it often fails to
      differentiate between recent and remote memories. This point is of particular
      importance to the on-going consolidation debate, as it often centers on a failure
      to detect an effect in the hippocampus in one or both conditions.

PMID- 17027784
TI  - Partnerships and innovations.

PMID- 17027785
TI  - Elbow capsulectomy for posttraumatic elbow stiffness.
AB  - PURPOSE: To determine factors associated with diminished elbow function and upper
      extremity-specific health status after elbow capsulectomy for posttraumatic
      stiffness. METHODS: Forty-six adult patients with posttraumatic elbow stiffness
      were evaluated an average of 48 months after open capsular excision. A second
      capsular excision was performed in 9 patients (29%). Stepwise multiple linear
      regression analysis was used to identify predictors of the American Shoulder and
      Elbow Surgeons Elbow Score, the Mayo Elbow Performance Index, and the
      Disabilities of the Arm, Shoulder, and Hand scores after all procedures. RESULTS:
      The average improvement in ulnohumeral motion after the index surgery for
      capsular release was 53 degrees . (The average flexion was 98 degrees .) The 9
      patients who had subsequent repeat elbow contracture release gained an additional
      24 degrees , leading to a final average flexion arc for the entire cohort of 103
      degrees . Multiple linear regression identified the American Shoulder and Elbow
      Surgeons pain score, persistent ulnar nerve dysfunction, and duration of follow
      up evaluation after the initial capsular release as independent predictors of a
      higher Disabilities of the Arm, Shoulder, and Hand questionnaire score; flexion
      arc and pain score as independent predictors of the Mayo Elbow Performance Index;
      and flexion arc, forearm arc, pain score, and persistent ulnar neuropathy as
      independent predictors of the American Shoulder and Elbow Surgeons score.
      CONCLUSIONS: Open elbow capsulectomy for posttraumatic elbow stiffness restores a
      near-100 degrees flexion arc on average. Second elbow releases provide limited
      additional motion in most patients. Final motion influences physician-based
      rating scales but not patient-specific health status (Disabilities of the Arm,
      Shoulder, and Hand questionnaire), which is dominated by pain and persistent
      ulnar neuropathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 17027786
TI  - Anatomy of the coronoid process.
AB  - PURPOSE: Coronoid injuries are classified according to the size of the coronoid
      fracture. The purpose of this study was to provide a detailed anatomic
      description of the coronoid process, with specific focus on the coronoid height,
      the coronoid width, and the olecranon-coronoid angle. METHODS: Thirty-five
      cadaveric arms were dissected. All soft tissue was removed and the ulna was
      disarticulated from the humerus, radius, and the carpal bones. A 3-dimensional
      digitizing system was used to locate 19 anatomic landmarks on each specimen. By
      using the 3-dimensional coordinates of the landmarks, the coronoid heights,
      proximal ulnar widths, and olecranon-coronoid angles were determined. RESULTS:
      The coronoid height, with its base defined by the trough of the trochlear notch
      and the slope change of the distal coronoid process, measured 15 mm and was 42%
      of the ulnar height. The coronoid height, with its base defined by the transverse
      groove of the sigmoid notch at the guiding ridge and the distal insertion of the
      brachialis muscle, measured 15 mm and was 43% of the ulnar height. The olecranon
      coronoid angle ranged between 33 degrees and 38 degrees . CONCLUSIONS: For
      lateral radiographic classification of coronoid fractures, coronoid height is
      best defined by the trough of the trochlear notch and the slope change of the
      distal coronoid process. For anatomic studies, coronoid height is best defined by
      the transverse groove of the sigmoid notch at the guiding ridge and the distal
      insertion of the brachialis muscle. The olecranon-coronoid angle is best defined
      by the angle formed by the lines from the olecranon tip through the coronoid tip
      and through the slope change of the distal coronoid process. The coronoid anatomy
      measurements reported in this study may help to improve coronoid fracture
      classification.

PMID- 17027787
TI  - Patterns of mRNA expression for matrix molecules and growth factors in flexor
      tendon injury: differences in the regulation between tendon and tendon sheath.
AB  - PURPOSE: Injuries to tendons, particularly flexor tendons, can lead to loss of
      function after healing due to adhesion formation and other complications. The aim
      of this study was to increase our understanding of the healing process in tendons
      and tendon sheaths to develop methods to affect the healing process and improve
      the outcome of tendon repair in the future. METHODS: In a rabbit model of flexor
      tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6
      for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant
      genes in tendon and tendon sheaths were measured using the reverse transcription
      polymerase chain reaction. Messenger RNA levels for a subset of relevant
      molecules at different time points after injury were compared with those of
      uninjured controls for tendons and tendon sheaths. RESULTS: Initially after
      injury, there was a shift in collagen expression with a marked increase in type
      III mRNA levels in both the tendon and tendon sheath, whereas those for collagen
      I increased only in the sheath at later time points. Aggrecan and versican mRNA
      levels were increased in both tissues, but temporal aspects of the changes were
      different. The mRNA levels for biglycan and lumican were all upregulated
      throughout the healing interval examined, whereas those for decorin were
      significantly decreased throughout in the tendon more so than the sheath. The
      mRNA levels for basic fibroblastic growth factor and transforming growth factor
      beta were elevated after injury in the tendon but not in the sheath. In contrast,
      mRNA levels for connective tissue growth factor were unaltered or decreased in
      both tissues throughout the interval assessed. CONCLUSIONS: Healing after injury
      to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of
      gene expression; however, the pattern in the tendon is very different from that
      in the sheath. These findings indicate that interventions developed to improve
      healing of these tissues will have to address these differences, because they
      will likely affect the outcomes.

PMID- 17027788
TI  - Revision of incompletely released trigger fingers by percutaneous release:
      results and complications.
AB  - PURPOSE: Percutaneous trigger digit release has been reported as a safe,
      effective, and quick procedure, but most surgeons convert to an open method for
      residual triggering after percutaneous release. This study evaluates the safety
      and efficacy of repeated percutaneous release for patients who had residual
      triggering after the initial percutaneous release. METHODS: Between January 2000
      and December 2002, 31 patients with a mean age of 55 years had a repeat
      percutaneous release to treat residual snapping or locking symptoms. Surgery was
      performed in the physician's office using the tip of a 19-gauge needle mounted on
      a 2-mL syringe. Patients received regular postoperative follow-up examinations at
      1, 6, and 12 weeks after surgery, and at the last visit, they completed a
      questionnaire regarding the duration of pain or swelling and when were they able
      to return to normal work. RESULTS: Twenty-eight digits (90%) were completely free
      of triggering. Three digits (10%) during follow-up evaluation had residual
      snapping. Of these, 1 patient had repeated percutaneous release, which achieved
      an excellent outcome; 1 patient favored an open-release technique, and 1 patient
      refused further treatment. No complications were identified at the final follow
      up examinations. Almost all patients returned to normal work within 3 days.
      CONCLUSIONS: Percutaneous A1 pulley release is an effective, safe, and convenient
      technique for the primary trigger finger and as a secondary procedure for
      patients who have residual triggering after the initial surgical procedure. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 17027789
TI  - Flexor tenosynovitis caused by Mycobacterium scrofulaceum: case report.
AB  - Atypical hand infections with Mycobacterium species are uncommon, and
      Mycobacterium scrofulaceum infections are rare. We present a case of flexor
      tenosynovitis caused by M scrofulaceum in a 66-year-old man with hypertension and
      diabetes.

PMID- 17027791
TI  - Arthroscopic repair of peripheral triangular fibrocartilage complex tears with
      suture welding: a technical report.
AB  - This report presents a method of arthroscopic repair of the peripheral triangular
      fibrocartilage complex tears that replaces traditional suture knots with
      ultrasonic welding of sutures. This will help eliminate potential causes of ulnar
      sided wrist discomfort during the postoperative period.

PMID- 17027790
TI  - Monopolar radiofrequency energy application to the dorsal extensor tendon
      apparatus in a canine model of tendon injury.
AB  - PURPOSE: To evaluate the use of monopolar radiofrequency energy (MRFE) to shorten
      stretched dorsal extensor tendon apparatus (DETA) tissues in a canine model.
      METHODS: Eleven adult canine forelimbs were used in this in vitro investigation.
      The DETA tissue was isolated between the metacarpophalangeal and proximal
      interphalangeal joints in the third and fourth digits of each limb. Isolated
      tissue was stretched in all but 2 of the digits (control group). After tissue
      stretching, monopular radiofrequency energy (MRFE) was applied to 18 of the
      digits at 1 of 3 temperatures: 50 degrees C, 60 degrees C, or 70 degrees C
      (stretch-treatment group). Two digits were treated identically, but MRFE was not
      applied (stretch-only group). Tissue length was measured before and after
      stretching and after treatment. Percent stretch, percent shortening, and percent
      original length were compared among the 3 stretch-treatment groups. All DETA
      specimens were examined with light microscopy. RESULTS: Histologic changes were
      apparent in the stretch-treatment and stretch-only specimens compared with
      controls. Percent stretch was not significantly different between groups. Percent
      shortening and percent original length were significantly lower and higher,
      respectively, in the 50 degrees C group than in the 60 degrees C and 70 degrees C
      stretch-treatment groups, which were not significantly different from each other.
      There was a significant linear correspondence between percent shortening and
      treatment temperature. CONCLUSIONS: The application of MRFE at a temperature of
      60 degrees C and a power of 10 W appears to shorten stretched DETA tissue to
      approximately the prestretched length in an in vitro canine model. Further
      investigation is necessary to determine the effect of treatment on the tissue's
      mechanical properties.

PMID- 17027792
TI  - Comparison between high-resolution MRI with a microscopy coil and arthroscopy in
      triangular fibrocartilage complex injury.
AB  - PURPOSE: To determine whether high-resolution magnetic resonance imaging (MRI)
      could detect injuries to the triangular fibrocartilage complex (TFCC). METHODS:
      Eleven patients who showed both a positive sign during the ulnocarpal stress test
      and tenderness at the distal end of the ulna had a high-resolution MRI using a 47
      mm diameter microscopy coil. Six regions of the TFCC were investigated for
      injury: the radial attachment, disc, ulnar attachment of the triangular
      fibrocartilage (TFC), ulnotriquetral ligament, palmar radioulnar ligament (PRUL),
      and dorsal radioulnar ligament (DRUL). Arthroscopy was performed subsequently on
      each patient. RESULTS: For injuries to the radial attachment or the disc of the
      TFC, a high-resolution MRI showed 100% sensitivity and 100% specificity compared
      with arthroscopy. In 3 cases in which injury to the ulnar attachment of the TFC
      was detected with MRI and examination showed a positive piano-key sign and distal
      radioulnar joint instability, only 1 injury was confirmed with arthrotomy. For
      MRI diagnosis of an ulnotriquetral ulnolunate attachment injury, the sensitivity
      was 100% and the specificity was 70%; however, 3 cases had false-positive
      results. Finally MRI had 100% sensitivity for detecting DRUL and PRUL injuries,
      although specificities were 75% and 83%, respectively. With MRI there were 2
      false-positive DRUL injury diagnoses and 1 false-positive PRUL injury diagnosis.
      CONCLUSIONS: High-resolution MRI using a microscopy surface coil allowed
      assessment of each TFCC component and showed a higher accuracy for diagnosing
      injuries to the radial attachment and the disc of the TFC compared with previous
      studies. High-resolution MRI, however, was not able to diagnose DRUL, PRUL, or
      ulnolunate ligament injuries accurately. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Diagnostic III.

PMID- 17027793
TI  - Trapeziectomy and intermetacarpal ligament reconstruction with the extensor carpi
      radialis longus for osteoarthritis of the trapeziometacarpal joint: surgical
      technique and long-term results.
AB  - PURPOSE: To report the long-term results of excision of the trapezium and
      intermetacarpal ligament reconstruction with the extensor carpi radialis longus
      for thumb trapeziometacarpal osteoarthritis. METHODS: Fourteen women and 5 men
      were retrospectively reviewed after an average of 9 years of follow-up
      evaluation. Trapeziectomy was performed and the extensor carpi radialis longus
      was harvested by a dorsoradial approach to reconstruct the intermetacarpal
      ligament. All patients wore a below-elbow cast for 6 weeks. Each patient had
      objective and subjective assessments. Thumb shortening was measured in follow-up
      radiographs. RESULTS: At the final follow-up evaluation, 16 (84%) patients were
      free of pain and 17 patients (89%) were satisfied with the results. Grip, key
      strength, and pinch strength improved compared with preoperative values. The
      trapezium space lost 14% of its height compared with preoperative values. Thumb
      motion improved, and there were no cases of instability. CONCLUSIONS: Resection
      arthroplasty of the trapezium with intermetacarpal ligament reconstruction with
      the extensor carpi radialis longus is an effective procedure that permits motion
      restoration and pain relief in the trapeziometacarpal joint in the long term
      without affecting thumb stability. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 17027794
TI  - Overgrowth after radial shortening for Kienbock's disease in a teenager: case
      report.
AB  - A 16-year-old boy was treated by a radial-shortening procedure for symptomatic
      stage IIIB Kienbock's disease with 4 mm negative ulnar variance. The osteotomy
      corrected the ulnar variance to negative 1 mm after surgery, but further negative
      ulnar variance of 9 mm occurred at follow-up evaluation as a result of radial
      overgrowth. The functional outcome was excellent with remodeling of the lunate.
      The possibility of overgrowth should be considered when contemplating a radial
      shortening osteotomy for Kienbock's disease in skeletally immature patients.

PMID- 17027795
TI  - In vivo elongation of the palmar and dorsal scapholunate interosseous ligament.
AB  - PURPOSE: To investigate the elongation of the palmar and dorsal subregions of the
      scapholunate interosseous ligament (SLIL) in healthy human subjects throughout a
      complete range of wrist motion. METHODS: The 3-dimensional in vivo kinematics of
      the scaphoid and lunate were determined in both wrists of 13 female and 13 male
      volunteers from computed tomography volume images. For each wrist the palmar and
      dorsal insertions of the SLIL were identified on reconstructed surface models of
      the scaphoid and lunate. The interbone distances between the palmar and dorsal
      sites were calculated for the neutral wrist position. Elongations were then
      calculated after applying the 3-dimensional kinematics to the scaphoid and
      lunate. A multiple linear regression model was used to determine if elongations
      varied significantly as a function of wrist flexion/extension and radioulnar
      deviation. RESULTS: From pure wrist extension to pure wrist flexion, the fibers
      of the SLIL at the palmar insertion site increased significantly, from 29%
      shortening to 27% elongation, and the dorsal insertion decreased from 26% to 4%
      shortening with respect to the fiber lengths in the neutral position. From pure
      radial deviation to pure ulnar deviation, the elongation of the palmar insertion
      significantly decreased from 9% elongation to 21% shortening. There was no
      notable change in dorsal elongation with wrist radioulnar deviation. The multiple
      linear regression model predicted that there would be minimal elongation of the
      palmar and dorsal fibers at the wrist position along the dart thrower's path from
      radial extension to ulnar flexion. CONCLUSIONS: In vivo elongation of the palmar
      and dorsal fibers of the SLIL varied with wrist position. The palmar fibers
      lengthened and the dorsal fibers shortened with wrist flexion and the opposite
      occurred with wrist extension. Scapholunate interosseous ligament elongation was
      minimal as the wrist was positioned along the dart thrower's path.

PMID- 17027796
TI  - The outcome of intra-articular distal radius fractures treated with fragment
      specific fixation.
AB  - PURPOSE: To assess the clinical, radiographic, and functional outcome of treating
      intra-articular distal radius fractures with fragment-specific fixation. METHODS:
      A retrospective review of 81 patients with 85 intra-articular distal radius
      fractures who were treated with fragment-specific fixation was performed. Minimum
      time to follow-up evaluation was 1 year, with a mean time of 32 months. The
      immediate postoperative films were compared with those taken at the final follow
      up evaluation. Radiographs of the uninjured wrist were also obtained at the final
      follow-up evaluation for comparison. Patients were examined for wrist and finger
      range of motion, deformity, and grip strength, and they completed a standard
      Disabilities of the Arm, Shoulder, and Hand outcome survey. RESULTS: According to
      Gartland and Werley scoring there were 61 excellent and 24 good results. Flexion
      and extension of the surgically treated wrist at the final follow-up evaluation
      averaged 85% and 91%, respectively, of the uninjured wrist; grip strength
      averaged 92% compared with the uninjured side. The average Disabilities of the
      Arm, Shoulder, and Hand outcome score for the injured wrist was 9. Sixty-two
      percent of patients achieved a 100 degrees arc of flexion and extension and
      normal forearm rotation by postoperative week 6. Radiographic alignment was
      maintained between immediate postoperative and final follow-up films, and there
      were no cases of symptomatic arthritis at the final follow-up evaluation.
      CONCLUSIONS: Fragment-specific fixation is a reasonable alternative for treating
      intra-articular fractures of the distal radius. At final follow-up evaluations,
      patients had good to excellent results with respect to range of motion, grip
      strength, radiographic alignment, and satisfaction scores. Stable fixation
      allowed starting active and passive motion of the wrist without compromising
      postoperative alignment. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 17027797
TI  - Functional outcome of en bloc excision and osteoarticular allograft replacement
      with the Sauve-Kapandji procedure for Campanacci grade 3 giant-cell tumor of the
      distal radius.
AB  - PURPOSE: Multiple options have been reported for reconstruction of Campanacci
      grade 3 giant-cell tumor of the distal radius after resection. In 1990, the
      senior author described an allograft reconstruction combined with a Sauve
      Kapandji procedure after distal radius resection and reported preliminary results
      in 3 patients. The purpose of this study was to assess with validated patient
      outcome surveys the intermediate to long-term outcomes of all patients treated
      with this surgery and to analyze their functional results and document tumor
      control. METHODS: All cases of distal radius osteoarticular allograft combined
      with the Sauve-Kapandji reconstruction for Campanacci grade 3 giant-cell tumors
      performed from 1986 to 2000 by a single surgeon were evaluated by clinical and
      radiologic examinations; the Disabilities of the Arm, Shoulder, and Hand
      questionnaire; the Short Form-36; and Mayo Wrist scores. RESULTS: Nine
      consecutive patients (7 women, 2 men) with an average age at follow-up evaluation
      of 42 years and with a Campanacci grade 3 giant-cell tumor of the distal radius
      formed the study population. Clinical follow-up time after reconstruction
      averaged 7 years. Examination showed an average of 51 degrees of extension and 19
      degrees of flexion of the wrist and 63 degrees of supination and 79 degrees of
      pronation of the forearm. Grip strength measured in 5 patients averaged 23 kg.
      The Disabilities of the Arm, Shoulder, and Hand questionnaire; the Short Form-36;
      and the Mayo Wrist scores averaged 15, 72, and 73, respectively. These scores
      indicate modest functional impact. No patient had tumor recurrence, metastases,
      nonunion, or proximal ulna instability. CONCLUSIONS: En bloc resection of a
      Campanacci grade 3 giant-cell tumor of the distal radius followed by
      reconstruction with an osteoarticular allograft and a Sauve-Kapandji procedure
      with autogenous bone graft results in a reasonable functional outcome at
      intermediate to long-term follow-up evaluation. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 17027798
TI  - Mini-screw fixation for the treatment of proximal interphalangeal joint dorsal
      fracture-dislocations.
AB  - PURPOSE: Surgical intervention may be necessary to treat unstable dorsal fracture
      dislocations of the proximal interphalangeal (PIP) joint of the hand. One method
      of stabilization is open reduction and internal fixation (ORIF). The purpose of
      this study was to assess the outcomes of ORIF for unstable dorsal fracture
      dislocations of the PIP joint using mini-screws via a volar approach. METHODS: A
      retrospective chart review with clinical follow-up evaluation was performed on 9
      patients who had ORIF for unstable dorsal fracture-dislocations of the PIP joint.
      The fracture fragment(s) from the middle phalangeal base were reduced and secured
      using mini-screws. RESULTS: A clinical evaluation was performed at an average of
      42 months after surgery. The average arc of motion for the involved PIP joint was
      70 degrees (range, 55 degrees -90 degrees ). The average PIP joint motion in the
      2 patients with 1 fracture fragment was 85 degrees , and the average PIP joint
      motion for the remaining 7 patients was 65 degrees . One joint was subluxated
      with an intra-articular screw. Nine patients had an average flexion contracture
      of 14 degrees . Seven patients had no pain, and 2 had pain only with heavy
      activity. CONCLUSIONS: Open reduction and internal fixation of unstable dorsal
      PIP joint fracture-dislocations using mini-screws can be considered if the
      fracture fragment(s) can accommodate the screws. The procedure attempts to
      restore the concave contour of the middle phalangeal base and permits early
      protected range of motion. The procedure should be approached cautiously,
      especially in the presence of comminution. Proximal interphalangeal joint range
      of motion is usually compromised; 8 of our 9 joints had a residual flexion
      contracture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 17027799
TI  - Radial collateral ligament injury of the index metacarpophalangeal joint: an
      underreported but important injury.
AB  - PURPOSE: To present the results of various treatment modalities based on injury
      grade of radial collateral ligament (RCL) injuries to the index
      metacarpophalangeal (MP) joint. METHODS: Fourteen patients were evaluated (4
      male, 10 female) with RCL injuries to the index MP joint. We defined injuries as
      Grade 1 (tenderness over RCL, no instability), grade 2 (laxity compared to the
      contralateral digit with a definite endpoint), or grade 3 (laxity without
      endpoint). Early presentation is defined as less than four weeks and late greater
      than four weeks. RESULTS: The average follow up was 24 months. Grade I-II
      injuries seen early (4 patients) treated with 4-6 weeks splinting had excellent
      results (normal ROM, stable pinch, pain free). There were no Grade I-II injuries
      seen late. Of Grade III injuries seen early (2 patients), attempted treatment in
      a removable splint was unsuccessful secondary to patient noncompliance;
      subsequently requiring primary repair of the collateral ligament which resulted
      in good outcomes. No Grade III injury seen early had attempted treatment in a
      cast. Eight patients presented late with Grade III injuries (4 elected for
      surgical intervention, 4 for nonsurgical management) and all had fair or poor
      outcomes. CONCLUSIONS: The significance of this injury remains underestimated and
      requires a high index of suspicion. Stable injuries seen early should be treated
      with prompt immobilization. Casting may be more effective than a removable
      splint. Grade III injuries seen early could possibly be treated with cast
      immobilization though close follow up is mandatory as surgical repair may be
      necessary in the high demand hand. All Grade III injuries treated late yielded
      fair to poor results requiring tendon reconstruction or fusion with significant
      alteration in hand function.

PMID- 17027800
TI  - Attitudes of hand surgeons, hand surgery patients, and the general public
      regarding psychologic influences on illness.
AB  - PURPOSE: Psychologic influences on illness are well recognized but infrequently
      addressed in the interactions of hand surgeons and patients. This study assessed
      the attitudes of hand surgery patients and hand surgeons regarding psychologic
      influences on illness and compared their attitudes with those of the general
      population. METHODS: An 8-question survey regarding participant's attitudes
      toward psychologic influences on illness was given to the general public (people
      waiting in an airport), patients presenting to a hand surgery practice, and
      members of the American Society for Surgery of the Hand. RESULTS: A total of 474
      surgeons, 85 patients, and 42 public participants completed the survey. There
      were no notable differences between patients and the general public, but the
      surgeons' attitudes were markedly different from both patients and the general
      public with respect to 4 items: the surgeons underestimated the openness of
      patients and the general public to discussing psychologic influences and
      willingness to see a psychologist or psychiatrist; and they were more supportive
      than the general public or patients regarding the opinion that the placebo effect
      reflects the strong influence of psychologic factors in healing and that
      psychologic stress often is expressed as a physical complaint. The distribution
      of patient responses showed 2 subgroups with respect to the idea that psychologic
      stress often is expressed as a physical complaint and with regard to willingness
      to see a mental heath professional, reflecting that a subset of patients with a
      hand illness may be resistant to these concepts. CONCLUSIONS: Hand surgery
      patients and the general public are not as aware of the psychologic influences on
      illness as are hand surgeons, but they are more willing to consider and discuss
      psychologic factors-and even psychologic treatment-than their surgeons realize.
      Surgeons' views may be colored by a few negative interactions with challenging
      patients, but a dialogue with our patients regarding the influence of psychologic
      issues on illness will be well received by most patients and may facilitate
      recovery.

PMID- 17027801
TI  - Hand span influences optimal grip span in male and female teenagers.
AB  - PURPOSE: To determine if there is an optimal grip span for determining the
      maximum handgrip strength in male and female teenagers, and if the optimal grip
      span was related to hand span. If they are related then the second aim was to
      derive a mathematic equation relating hand span and optimal grip span. METHODS:
      One hundred healthy teenage boys (15.1 +/- 1.1 y) and 106 girls (15.4 +/- 1.3 y)
      were evaluated (age range, 13-18 y). Each hand was randomly tested on 10
      occasions using 5 different grip spans, allowing a 1-minute rest between
      attempts. The hand span was measured from the tip of the thumb to the tip of the
      small finger with the hand opened as wide as possible. RESULTS: The results
      showed that an optimal grip span to determine the maximum handgrip strength was
      identified for both genders, and the optimal grip span and hand span correlated
      in both genders. CONCLUSIONS: The results suggest that there is an optimal grip
      span to which the dynamometer should be adjusted when measuring handgrip strength
      in teenagers. The optimal grip span was influenced by hand span in both genders.
      For males the optimal grip span can be derived from the equation y = x/7.2 + 3.1
      cm, and for females from the equation y = x/4 + 1.1 cm. where y is the optimal
      grip span and x is the hand-span. These equations may improve the reliability and
      accuracy of the results and may guide clinicians and researchers in selecting the
      optimal grip span on the hand dynamometer when measuring handgrip strength in
      teenagers.

PMID- 17027802
TI  - Outcomes research in hand surgery: where have we been and where should we go?
AB  - PURPOSE: The outcomes movement began in response to a national emphasis to
      control cost and to limit geographic variation in medical services. The impact of
      the outcomes movement on hand surgery research is unknown. We conducted a
      systematic review of hand surgery studies to assess the past and current states
      of outcomes research in this specialty. METHODS: A systematic review of hand
      surgery outcomes studies was conducted in The Journal of Hand Surgery (American
      and British volumes) from 1988 to 2004. A Medline search using the 11 Agency for
      Healthcare Research and Quality categories of outcomes studies was performed.
      Studies were rated for study design, data endpoints, and level of impact using
      the Agency for Healthcare Research and Quality-designated impact levels. RESULTS:
      A total of 2,236 studies were identified, and 1,188 were included in the
      analysis. Most studies were rated as level 1 impact (N = 1,090, 92%), and a small
      number of studies were level 4 impact (N = 98, 8%). Thirty-nine percent were
      prospective and 45% (N = 529) were retrospective descriptive studies. Data
      gathered in studies included objective clinical measures (N = 672, 57%), quality
      of life (N = 374, 31%), morbidity (N = 401, 34%), subjective clinical measures (N
      = 27, 16%), cost (N = 185, 2%), and mortality (N = 11, 1%). CONCLUSIONS: Our
      systematic review of hand surgery outcomes studies found that much of the
      research is confined to testing new or existing surgical techniques (level 1
      impact). We found a small number of studies that did show improvement in patient
      outcomes as a result of an intervention (level 4 impact). The future direction of
      outcomes studies should consider the impact of the research goals to change
      patient or physician behavior to enhance health parameters. More research on
      economic analysis needs to be conducted in hand surgery to meet the national goal
      of containing cost and improving the quality of health care.

PMID- 17027803
TI  - Outcome after repair of the scapholunate interosseous ligament and dorsal
      capsulodesis for dynamic scapholunate instability due to trauma.
AB  - PURPOSE: To retrospectively assess outcomes in 17 patients treated with
      scapholunate (SL) interosseous ligament repair and capsulodesis for dynamic SL
      instability due to trauma. METHODS: A retrospective review of 17 consecutive
      patients included clinical and radiographic examinations to determine outcome
      after SL interosseous ligament repair and dorsal capsulodesis. The average age at
      the time of surgery was 36 years, and the postoperative follow-up period averaged
      66 months. Outcome measures included the Mayo wrist evaluation system and
      Disabilities of the Arm, Shoulder, and Hand questionnaire scores. Pain complaints
      were measured on a 10-point visual analog scale. RESULTS: Preoperative and
      postoperative measurements, respectively, for all patients were obtained as
      follows: SL gap, 2 versus 3 mm; stress views of the SL gap, 3 versus 4 mm; SL
      angle, 49 degrees versus 54 degrees ; capitolunate angle, 4 degrees versus 7
      degrees . Grip strength was 82% of the uninjured side at the final follow-up
      evaluations. Pain averaged a 3 out of 10 before and after surgery. Surgery was
      completed an average of 22 weeks from injury. Disabilities of the Arm, Shoulder,
      and Hand questionnaire scores averaged 31, indicating wrist impairment. Three
      patients developed degenerative changes noted on postoperative x-rays. When
      patients were evaluated based on daily job requirements (strenuous vs
      nonstrenuous) there were statistically significant differences. Nonstrenuous job
      requirements had lower pain scores; better Disabilities of the Arm, Shoulder, and
      Hand questionnaire scores; better Mayo outcomes; better grip strength; and
      decreased SL gap on stress views. Flexion and extension of the wrist were better
      in the nonstrenuous group but did not reach statistical significance.
      CONCLUSIONS: Prior reports evaluating patients for SL ligament repair appeared to
      be favorable in short-term (1- to 2-y) follow-up periods. In the present report,
      for patients followed up for an average of 66 months after surgery, the results,
      clinically and radiographically, appear to deteriorate in those who place high
      demands on the wrists on a daily basis. Although the numbers in the present study
      are small, they indicate that SL ligament repair with dorsal capsulodesis may
      have a place for patients who have normal preoperative static unloaded x-rays and
      sufficient ligament for repair and who do not place high demands on the wrists on
      a daily basis. The ideal procedure for this difficult problem continues to remain
      elusive. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 17027805
TI  - Glomus tumors.
AB  - Glomus tumors are rare vascular tumors that are found most commonly in the hand.
      Although the tumors are benign, they can cause intense focal pain. Patients often
      go undiagnosed or misdiagnosed for many years because the tumors are small,
      usually not palpable, and have varying presentations. A combination of magnetic
      resonance imaging and clinical examination is used to support the diagnosis.
      Surgical excision normally provides complete pain relief. An awareness of the
      diagnosis is critical to preventing an unnecessary delay in treatment.

PMID- 17027804
TI  - Arthroscopic treatment of glenohumeral instability.
AB  - Arthroscopic treatment of glenohumeral instability using modern suture anchor
      techniques has reported recurrence rates equal to open techniques, even in high
      demand contact athletes. Compared with open procedures, arthroscopic
      stabilization leads to less morbidity and less stiffness, leading to improved
      postoperative function, especially in overhead athletes. This article highlights
      the technical aspects of arthroscopic treatment of anterior glenohumeral
      instability.

PMID- 17027806
TI  - Refinements in the technique for repair of the accessory nerve.
AB  - Trapezius muscle palsy after accessory nerve injury leads to periscapular pain
      and shoulder motion deficit. The results of accessory nerve repair generally are
      good, but surgery is difficult. The difficulty consists of finding the nerve
      stumps that are embedded in fat and scar tissue from previous surgeries or
      injuries. Five patients with accessory nerve lesions had surgery and grafting of
      the accessory nerve. We dissected the proximal stump of the accessory nerve
      within the fibers of the sternocleidomastoid muscle and in the vicinity of the
      greater auricular nerve. To achieve dissection of the distal nerve stump, the
      deep cervical fascia was detached from the trapezius muscle 3 cm cephalad to the
      clavicle. The detached fascia and the trapezius muscle were flipped similar to
      book pages. The motor branches entering the trapezius muscle were visualized and
      followed toward the accessory nerve. A sural nerve graft with a mean length of
      6.6 cm was used for grafting. Uncomplicated identification of the nerve stumps
      was possible in all patients. After accessory nerve grafting, pain and motion
      consistently improved in all patients. The technique proposed here ensures
      reliable and rapid identification of the divided stumps of the accessory nerve.

PMID- 17027807
TI  - Aberrant nerve in limited open carpal tunnel release.

PMID- 17027809
TI  - A comparative study of ulnar shortening osteotomy by the freehand technique
      versus the Rayhack technique.

PMID- 17027810
TI  - Comparative study of the whisky aroma profile based on headspace solid phase
      microextraction using different fibre coatings.
AB  - A dynamic headspace solid-phase microextraction (HS-SPME) and gas chromatography
      coupled to ion trap mass spectrometry (GC-(IT)MS) method was developed and
      applied for the qualitative determination of the volatile compounds present in
      commercial whisky samples which alcoholic content was previously adjusted to 13%
      (v/v). Headspace SPME experimental conditions, such as fibre coating, extraction
      temperature and extraction time, were optimized in order to improve the
      extraction process. Five different SPME fibres were used in this study, namely,
      poly(dimethylsiloxane) (PDMS), poly(acrylate) (PA), Carboxen
      poly(dimethylsiloxane) (CAR/PDMS), Carbowax-divinylbenzene (CW/DVB) and Carboxen
      poly(dimethylsiloxane)-divinylbenzene (CAR/PDMS/DVB). The best results were
      obtained using a 75 microm CAR/PDMS fibre during headspace extraction at 40
      degrees C with stirring at 750 rpm for 60 min, after saturating the samples with
      salt. The optimised methodology was then applied to investigate the volatile
      composition profile of three Scotch whisky samples--Black Label, Ballantines and
      Highland Clan. Approximately seventy volatile compounds were identified in the
      these samples, pertaining at several chemical groups, mainly fatty acids ethyl
      esters, higher alcohols, fatty acids, carbonyl compounds, monoterpenols, C13
      norisoprenoids and some volatile phenols. The ethyl esters form an essential
      group of aroma components in whisky, to which they confer a pleasant aroma, with
      "fruity" odours. Qualitatively, the isoamyl acetate, with "banana" aroma, was the
      most interesting. Quantitatively, significant components are ethyl esters of
      caprilic, capric and lauric acids. The highest concentration of fatty acids, were
      observed for caprilic and capric acids. From the higher alcohols the fusel oils
      (3-methylbutan-1-ol and 2.phenyletanol) are the most important ones.

PMID- 17027811
TI  - Confirmatory and quantitative analysis using experimental design for the
      extraction and liquid chromatography-UV, liquid chromatography-mass spectrometry
      and liquid chromatography-mass spectrometry/mass spectrometry determination of
      quinolones in turkey muscle.
AB  - The aim of this work is to established methods for determination of quinolones
      (ciprofloxacin, danofloxacin, enrofloxacin, difloxacin and flumequine), regulated
      by European Union, and sarafloxacin in turkey muscle. An experimental design has
      been applied for the optimization of the factors that influence the extraction of
      quinolones from turkey muscle in order to determine the experimental conditions
      for their extraction with high recoveries. Liquid chromatography with ultraviolet
      detection (LC-UV), liquid chromatography-mass spectrometry (LC-MS) and liquid
      chromatography tandem mass spectrometry (LC-MS/MS) have been used for the
      simultaneous quantification of quinolones antibiotics in turkey muscle. The
      proposed methods have been validated according to the Food Drugs Administration
      guideline and presents the limit of quantification below the maximum residue
      limits established by the European Union for quinolones in turkey muscle. The
      methods developed have been applied to quantification of enrofloxacin and its
      main metabolite ciprofloxacin in samples of turkey muscle obtained from animals
      treated with enrofloxacin.

PMID- 17027812
TI  - A level set method for determining critical curvatures for drainage and
      imbibition.
AB  - An accurate description of the mechanics of pore level displacement of immiscible
      fluids could significantly improve the predictions from pore network models of
      capillary pressure-saturation curves, interfacial areas and relative permeability
      in real porous media. If we assume quasi-static displacement, at constant
      pressure and surface tension, pore scale interfaces are modeled as constant mean
      curvature surfaces, which are not easy to calculate. Moreover, the extremely
      irregular geometry of natural porous media makes it difficult to evaluate surface
      curvature values and corresponding geometric configurations of two fluids.
      Finally, accounting for the topological changes of the interface, such as
      splitting or merging, is nontrivial. We apply the level set method for tracking
      and propagating interfaces in order to robustly handle topological changes and to
      obtain geometrically correct interfaces. We describe a simple but robust model
      for determining critical curvatures for throat drainage and pore imbibition. The
      model is set up for quasi-static displacements but it nevertheless captures both
      reversible and irreversible behavior (Haines jump, pore body imbibition). The
      pore scale grain boundary conditions are extracted from model porous media and
      from imaged geometries in real rocks. The method gives quantitative agreement
      with measurements and with other theories and computational approaches.

PMID- 17027813
TI  - A new glance at ruthenium sorption mechanism on hydroxy, carbonate, and fluor
      apatites: Analytical and structural studies.
AB  - The sorption mechanism of Ru3+ ions on hydroxy (HAp), carbonate (CO3HAp), and
      fluor apatites (FAp) has been studied in detail. Ru apatites were obtained by
      reaction of the apatites with RuCl3 in aqueous solution. The structure and
      composition of the ruthenium-modified apatites were studied by several
      techniques: elemental analysis, XRD, EXAFS, IR, NMR, SEM-EDS, TEM, and thermal
      analysis. The amount of Ru in the modified apatite varies from 7.8 to 10.5 wt%
      and is not related to the initial composition or the specific surface area of the
      apatite. The different characterization techniques show that in the Ru-modified
      apatites Ru is surrounded by six oxygen atoms and do not contain any chlorine.
      For Ru-HAp and Ru-CO3HAp the new phase is amorphous whereas it is crystalline for
      FAp. The catalytic oxidation ability is higher for Ru-HAp and Ru-CO3HAp compared
      to Ru-FAp apatite in the oxidation of benzylic alcohol.

PMID- 17027815
TI  - New ways of measuring blood pressure.

PMID- 17027816
TI  - Blood pressure variability and cardiovascular risk in treated hypertensive
      patients.
AB  - BACKGROUND: The independent prognostic value of blood pressure (BP) variability
      in treated hypertension is not yet clear. We investigated the relationship
      between BP variability, evaluated by noninvasive monitoring, and cardiovascular
      outcome in treated hypertensive patients. METHODS: The occurrence of fatal and
      nonfatal cardiovascular events was evaluated in 1472 treated patients. Subjects
      with the standard deviation of daytime or night-time systolic BP below or above
      the median of the population were classified as having low or high BP
      variability. Specifically, 738 and 734 patients had low and high daytime BP
      variability, respectively, and 739 and 733 subjects had low and high night-time
      BP variability, respectively. RESULTS: During follow-up (4.88 +/- 2.9 years,
      range 0.2-11.6 years) there were 119 events. The event rates per 100 patient
      years in subjects with low and high BP variability according to daytime BP were
      1.18 and 2.01, respectively, and in those with low and high BP variability
      according to night-time BP were 1.2 and 2.05, respectively. Event-free survival
      was significantly different between the low and high BP variability groups (P =
      .006 for both daytime and night-time BP). However, after adjustment for other
      covariates in a Cox multivariate analysis, the adverse prognostic relevance of
      high BP variability was no longer detectable, whereas age, smoking habit, LDL
      cholesterol, diabetes, previous events, LV hypertrophy, and daytime or night-time
      systolic BP resulted independent predictors of risk. CONCLUSIONS: Increased BP
      variability is associated with higher incidence of cardiovascular events, but
      also with other relevant prognostic factors. Indeed, in multivariate analysis the
      possible adverse prognostic impact of BP variability is no longer evident. Thus,
      in treated hypertension, BP variability evaluated by noninvasive monitoring is
      not an independent predictor of outcome.

PMID- 17027817
TI  - Renal dysfunction predicts attenuation of ischemic heart disease mortality risk
      from elevated glucose among treated hypertensive patients.
AB  - BACKGROUND: Impaired fasting glucose (IFG) and renal dysfunction are recognized
      as independent risk factors for adverse heart outcomes. This study examines the
      interaction of renal dysfunction and IFG (>or=110 mg/dL) upon the risk of
      ischemic heart disease (IHD) mortality among treated hypertensive subjects.
      METHODS: Subjects were 9918 participants in a worksite-based antihypertensive
      treatment program in New York City (1981 to 1999) with baseline estimated
      glomerular filtration rate (GFR) >30 mL/min/1.73 m2 (estimated by Cockcroft and
      Gault formula) observed for a mean follow-up of 9.6 +/- 5.0 years (range 0.5-20.0
      years). Outcome events were IHD deaths (n = 337) ascertained from the National
      Death Index. Cox proportional hazard models were constructed for the entire
      cohort to assess the interaction and then stratified by moderate renal
      dysfunction (MRD; GFR 60-30 mL/min/1.73 m2). Age and sex adjusted rates were
      calculated within MRD and NKF-defined categories. Hazard ratios for IFG were
      calculated within MRD strata. RESULTS: The interaction product term of MRD and
      IFG significantly improved (P = .001) a Cox proportional hazard model after
      adjusting for known cardiovascular risk factors. Among participants with GFR
      >or=60 mL/min/1.73 m2 the IHD mortality hazard ratio for IFG was 1.47 (95% CI =
      1.09-1.99; P = .012). Conversely, among participants with MRD, the IHD mortality
      hazard ratio for IFG was 0.44 (95% CI = 0.21-0.94; P = .034). CONCLUSIONS: These
      results suggest an attenuating effect modification of GFR on IHD mortality risk
      associated with IFG among treated hypertensive subjects. Whether the observed
      qualitative interaction is simply statistical or reflects a biological counter
      regulatory mechanism requires additional study.

PMID- 17027818
TI  - Effects of 24-h shift work in the emergency room on ambulatory blood pressure
      monitoring values of medical residents.
AB  - BACKGROUND: Medical residency is marked by long work hours and shift work. The
      acute effects of these factors on the blood pressure (BP) of medical residents
      have not been adequately evaluated. METHODS: A total of 61 medical residents
      underwent to ambulatory blood pressure monitoring (ABPM) during a 24-h shift work
      in the emergency room (ER) and during a common working day. RESULTS: Both mean 24
      h systolic and diastolic BP (DBP) and mean diastolic BP readings during sleep
      were higher during the 24-h shift work in the ER than during common working day
      (117 v 113 mm Hg, P < .05; 73 v 69 mm Hg, P < .05; and 61 v 58 mm Hg, P < .05,
      respectively). Abnormally high mean BP readings were more frequent during the 24
      h shift work in the ER than in common working day (19 v 8, P < .05). Pressure
      load, nocturnal BP fall and pulse pressure values were similar in these two
      different working situations. CONCLUSION: Working in the ER on a 24-h shift leads
      to abnormal BP behavior in medical residents, thus suggesting that this type of
      work may be a risk factor for cardiovascular disease.

PMID- 17027819
TI  - Rate of morning increase in blood pressure is elevated in hypertensives.
AB  - BACKGROUND: We applied a new logistic curve fitting procedure to ambulatory blood
      pressure (ABP) recordings to determine whether the rate of increase in systolic
      (SBP), mean (MBP) and diastolic blood pressure (DBP) and heart rate (HR) in the
      morning is related to the level of BP in subjects. METHODS: The rate of
      transition in the morning and evening period was determined using a six-parameter
      double-logistic equation applied to 528 ABP recordings from a cardiovascular risk
      assessment clinic. Based on daytime BP (MBP, SBP, or DBP), the upper quartile
      (UQ, n = 132) and lower quartile (LQ) were compared. RESULTS: Subjects in the UQ
      of daytime MBP were hypertensive and showed greater day-night differences
      compared to normotensive subjects in the LQ (29 +/- 1 mm Hg for MBP compared to
      20 +/- 1 mm Hg). The rate of morning increase in SBP and DBP was 42% and 30%
      greater in UQ subjects compared to the LQ subjects (P < .05). The rates of
      evening decrease in all BPs were 69% to 84% greater in the subjects in the UQ.
      Similar results were obtained if subjects were divided according to daytime SBP
      or DBP. The rate of morning increase in MBP was correlated with daytime BP, but
      not night-time or 24 h MBP. CONCLUSIONS: The rate of morning increase in BP is
      greater in those subjects with the highest daytime BP. The exaggerated rate of
      morning increase in BP in this group, which were all hypertensive, may also be
      important for greater cardiovascular risk.

PMID- 17027820
TI  - Exaggerated morning surge in blood pressure in hypertension.

PMID- 17027821
TI  - Aortic augmentation index is inversely associated with cardiorespiratory fitness
      in men without known coronary heart disease.
AB  - BACKGROUND: We investigated whether the aortic augmentation index (AIx), a
      measure of arterial wave reflection and stiffness, is associated with
      cardiorespiratory fitness in men without known coronary heart disease (CHD).
      METHODS: Asymptomatic men (n = 201, mean age 51 +/- 9.2 years) referred for a
      screening exercise electrocardiogram (ECG) underwent applanation tonometry to
      obtain radial artery pulse waveforms, and an ascending aortic pressure waveform
      was derived by a transfer function. The AIx is the difference between the first
      and second systolic peak of the ascending aortic pressure waveform, expressed as
      a percentage of the pulse pressure. Cardiorespiratory fitness was assessed by
      maximal oxygen consumption (VO2max mL/min/kg) during a symptom-limited graded
      exercise test. Multivariable regression analyses were used to identify
      significant independent determinants of AIx and of VO2 max. RESULTS: Diabetes was
      present in 2.5% of subjects, 34.8% had history of smoking, and 29% were
      hypertensive. Mean (+/- SD) AIx was 19.9% +/- 9.0% and mean VO(2 max) was 33.9 +/
      6.4 mL/min/kg. In a multivariable linear regression model, AIx was positively
      associated with age, hypertension, and history of smoking and inversely with
      heart rate, height, and body mass index (BMI). The VO2 max was significantly
      inversely related to AIx after adjustment for age, heart rate, height, and BMI (r
      = -0.22, P = .002), after further adjustment for CHD risk factors (total
      cholesterol, HDL-cholesterol, history of smoking, diabetes, hypertension) (P =
      .006), and after additional adjustment for behavioral factors (physical activity
      score, alcohol intake, and percent body fat) (P = .022). CONCLUSIONS: These
      findings indicate that AIx, a measure of arterial wave reflection and stiffness,
      is inversely associated with cardiorespiratory fitness in men without CHD.

PMID- 17027822
TI  - Relationship of circulating biomarkers of inflammation and hemostasis with
      preclinical atherosclerotic burden in nonsmoking hypercholesterolemic men.
AB  - BACKGROUND: Relations of mediators of inflammation and hemostasis with
      preclinical atherosclerosis have been poorly analyzed. The aim of this study was
      to test potential associations of these blood markers with indicators of
      cardiovascular risk and atherosclerotic burden in asymptomatic, nonsmoking,
      hypercholesterolemic men. METHODS: A total of 87 men underwent cardiovascular
      risk assessment by means of 10-year Framingham risk calculation (median 9%) and
      atherosclerotic burden evaluation by means of ultrasonographic measurement of
      common carotid intima-media thickness and assessment of atherosclerotic plaques
      at three arterial sites (three-site plaques). RESULTS: Of the markers C-reactive
      protein, tumor necrosis factor-alpha, interleukin-10, factor VIIc, fibrinogen,
      plasminogen activator inhibitor-activator, soluble intercellular adhesion
      molecule-1, soluble P-selectin (sP-selectin), and von Willebrand factor, only sP
      selectin was positively and independently associated with high Framingham risk
      score (>9%) (71.7 +/- 3.6 ng/mL, n = 33 v 59.6 +/- 2.8, n = 54; mean +/- SEM; P <
      .05) and with three-site plaques (75.4 +/- 5.7 ng/mL, n = 14 v 62.0 +/- 2.5, n =
      73; P < .05). After adjustment for all of the above markers and for
      cardiovascular risk factors, odd ratios of having high Framingham risk and three
      site plaques were 3.38 (1.43 to 10.21) and 5.23 (1.74 to 23.52) respectively, per
      1-standard deviation increase in sP-selectin. CONCLUSIONS: These results confirm
      that among several hemostasis and inflammation mediators, only sP-selectin blood
      level was associated with preclinical atherosclerosis. It might confer to sP
      selectin measurement a clinical usefulness for detecting and managing high
      cardiovascular risk in primary prevention.

PMID- 17027823
TI  - Physical activity duration, intensity, and arterial stiffening in postmenopausal
      women.
AB  - BACKGROUND: Aerobic exercise training is associated with lower central arterial
      stiffness, but little information exists on the effects of physical activity
      intensity or duration on central arterial stiffness. Using a cross-sectional and
      interventional approach, we tested the hypothesis that both moderate and vigorous
      physical activity reduce central arterial stiffness in postmenopausal women.
      METHODS: Carotid arterial stiffness (via ultrasound and applanation tonometry)
      and duration of physical activity at low, moderate, and vigorous intensities (via
      electronic accelerometer) were measured in 103 apparently healthy sedentary or
      recreationally active women 47 to 82 years of age. Moderate intensity physical
      activity was defined as 4.0 to 6.0 metabolic equivalents (MET) in subjects aged
      <65 years and as 3.0 to 5.0 MET in subjects >or=65 years. A subgroup of 17
      sedentary subjects was randomly assigned to moderate (n = 8) or vigorous (n = 9)
      intensity cycling exercise training (900 kcal/week, three to five sessions per
      week, for 12 weeks). Carotid arterial stiffness was measured before and after
      training. RESULTS: Carotid beta-stiffness index was significantly correlated with
      the duration of moderate and vigorous intensity physical activity (r = -0.25 and
      r = -0.22) even after adjustment for age, height, and mean BP. Carotid beta
      stiffness index significantly decreased after moderate and vigorous intensity
      cycling training. There were no significant group differences in the magnitude of
      beta-stiffness index change even after adjustment for expected confounders (eg,
      baseline beta-stiffness index, height, body mass index, heart rate, and post
      training body mass, body mass index, and mean BP). CONCLUSIONS: These results
      suggest that both moderate and vigorous physical activities have favorable
      effects on central arterial stiffness in postmenopausal women.

PMID- 17027824
TI  - The benefits of exercise for arterial stiffness.

PMID- 17027825
TI  - Chronic effect of combined treatment with omapatrilat and adrenomedullin on the
      progression of heart failure in rats.
AB  - BACKGROUND: We and other investigators have reported that short- and long-term
      treatment with adrenomedullin has beneficial effects in heart failure. This study
      examined the effects of long-term treatment with a vasopeptidase inhibitor plus
      adrenomedullin in a model of heart failure in rats and assessed potential
      mechanisms of action. METHODS: Dahl salt-sensitive rats aged 11 weeks were
      randomly divided into three groups: an omapatrilat group, an omapatrilat plus
      adrenomedullin group, and an untreated group. The effects of these treatments
      were evaluated after 7 weeks of treatment. RESULTS: Omapatrilat monotherapy
      significantly improved left ventricular weight (LVW), blood pressure (BP), and
      central hemodynamics as compared with the untreated group. Omapatrilat decreased
      the gene expression levels of adrenomedullin and atrial natriuretic peptide (ANP)
      in the left ventricle. In addition, omapatrilat decreased mRNA levels of
      transforming growth factor-beta (TGF-beta), collagen I, collagen III, plasminogen
      activator inhibitor-1 (PAI-1), and intercellular adhesion molecule-1 (ICAM-1) in
      the left ventricle, and omapatrilat decreased perifibrosis score and myocyte area
      histologically. Omapatrilat plus adrenomedullin further improved LVW, central
      hemodynamics, and mRNA expression of TGF-beta, collagen I, collagen III, PAI-1,
      and ICAM-1 without changing BP. Omapatrilat plus adrenomedullin further reduced
      mRNA levels of ANP and adrenomedullin without altering levels of ANP or
      adrenomedullin in plasma. Interestingly, omapatrilat slightly decreased mRNA
      levels of subunits of NADPH oxidase, whereas omapatrilat plus adrenomedullin
      further decreased these variables. CONCLUSIONS: Our results suggest that combined
      treatment with adrenomedullin and omapatrilat may be a new strategy for the
      management of heart failure, acting partly by inhibition of the extracellular
      matrix gene, adhesion molecule, antifibrinolysis, and oxidative stress
      production.

PMID- 17027826
TI  - Left ventricular hypertrophy in patients with autonomic failure.
AB  - BACKGROUND: In autonomic failure (AF), supine hypertension may predispose
      patients to end-organ damage. The pathophysiology of hypertensive heart disease
      in AF is not known. The aim of the present study was to evaluate the prevalence
      and predisposing factors of left ventricular hypertrophy (LVH) in patients with
      AF. METHODS: We studied 25 patients with AF (67 +/- 8 years); 80% were being
      treated for orthostatic hypotension. Twenty patients with essential hypertension
      (68 +/- 6 years) were considered as the control group. All subjects underwent
      echocardiography for measurement of left ventricular mass (LVM). The patients
      with AF underwent a 24-h BP monitoring and long-term blood pressure (BP)
      variability was calculated as standard deviation (SD) of the average of the half
      hour mean values. RESULTS: The LVM is comparable in patients with AF and
      hypertensive controls (145 +/- 35 g/m2 v 127 +/- 32 g/m2, P = .07). The
      proportion of patients with LVH is similar in both populations (AF 80%,
      hypertensive 70%). The patients with AF were divided into two groups, with and
      without LVH. The SDs are significantly higher in AF patients with LVH than in
      those with normal LVM (SD 24-h systolic BP: 22 +/- 4 v 14 +/- 1 mm Hg, P = .001).
      CONCLUSIONS: A high proportion of patients with AF show LVH. The LVM values are
      comparable with those of patients with essential hypertension. The development of
      LVH seems to depend on high BP variability, characteristic of AF patients.
      Detection of LVH may help in the choice of treatment for orthostatic hypotension
      and in the prevention of heart failure.

PMID- 17027827
TI  - Serum uric acid is a determinant of metabolic syndrome in a population-based
      study.
AB  - BACKGROUND: Determination of serum uric acid concentrations and role in risk of
      metabolic syndrome (MS) were investigated in 1877 participants in a cross
      sectional population-based study including a brief follow-up. METHODS: The MS was
      identified by modified criteria of the Adult Treatment Panel III, and coronary
      heart disease (CHD) by clinical findings and Minnesota coding of resting
      electrocardiograms. Uric acid concentrations were measured by the uricase method.
      RESULTS: Metabolic syndrome was present in 39.1% of the cohort. Linear regression
      analysis of uric acid levels in a model comprising 13 variables identified
      gender, waist girth, total cholesterol (TC), alcohol usage, triglycerides, log C
      reactive protein (CRP), and log gamma-glutamyl transferase (GGT), and in women
      diuretic use and elevated blood pressure (BP), as significant independent
      covariates whereby the largest contribution (1.6 mg/dL) was generated by waist
      girth. Logistic regression analysis of serum uric acid for MS disclosed for the
      top versus the bottom tertile an odds ratio (OR) of 1.89 (95% confidence interval
      [CI]: 1.45-2.46) in men and women combined, after adjustment for sex, age, TC,
      log CRP, log GGT, alcohol, and diuretic drug use, presence of diabetes/impaired
      fasting glucose, elevated BP, and smoking status. This corresponded to an
      increase by 35% in MS likelihood for each 1 SD uric acid increment. This rate
      declined to a significant 15% by inclusion of waist girth into the model. The OR
      of uric acid concentrations for prevalent and incident CHD, adjusted for age, MS,
      smoking, and diuretic use, was not significant among women and only tended toward
      significance in men. CONCLUSIONS: Abdominal obesity is the main determinant of
      uric acid variance. An increment of 1 SD in serum uric acid levels are associated
      in both sexes with a 35% higher MS likelihood, independent of 10 risk factors
      related to MS. After adjustment for waist girth, a more modest but significant
      likelihood persists, which suggests that serum uric acid is a determinant of MS.

PMID- 17027828
TI  - Reviewer's perspective of the role of uric acid.

PMID- 17027829
TI  - Evening-morning differences in blood pressure in sleep apnea syndrome: effect of
      gender.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. In the
      current study we sought to determine whether the evening-morning differences in
      blood pressure (BP) would correlate with the severity of OSA and whether there
      are gender-related differences. METHODS: A total of 2009 consecutive patients
      referred to sleep examination because of suspected sleep apnea were
      retrospectively included. The patients comprised 1566 men, of whom 870 were
      nonhypertensive (non-HT) and 696 hypertensive (HT) and 443 women, of whom 258
      were non-HT and 185 HT. Four BP measurements, two in the evening and two in the
      morning, were taken. The relationship between evening-morning differences in BP
      and the number of apneas/hypopneas divided by hours of sleep (AHI) were analyzed
      separately for HT and non-HT men and women. RESULTS: In men, increase in AHI was
      associated with increase in morning BP, and the evening-morning difference for
      both systolic and diastolic BP became negative. These trends were found to be
      significant by linear regression analyses both for HT (for systolic BP, r = 0.75,
      P < .05, for diastolic BP r = 0.96, P < .05) and non-HT patients (for systolic BP
      r = 0.93, P < .05, for diastolic BP r = 0.94, P < .05). In women (unlike in men),
      increasing AHI was not associated with a linear increase in the evening-morning
      BP differences. None of the regression lines fitted to the data was significant.
      CONCLUSIONS: Our results demonstrate that the evening to morning difference in BP
      in men with OSA is linearly related to the severity of OSA, both in patients with
      HT and in those with non-HT. These results may have practical relevance in
      screening for patients with OSA and may have prognostic clinical value in
      predicting future cardiovascular events.

PMID- 17027830
TI  - The sympathetic drive after acute myocardial infarction in hypertensive patients.
AB  - BACKGROUND: Sympathetic activation occurs in hypertension (HT) and after acute
      myocardial infarction (AMI) and is related to greater cardiovascular risk. Also,
      AMI in patients with HT (AMI-HT) carries greater risk than that in normal
      subjects (AMI-NT). We therefore planned to determine whether the sympathetic
      activation and its duration after AMI are greater in patients with antecedent HT
      than in patients with normal arterial pressure (NT). METHODS: In 68 matched
      subjects with uncomplicated AMI-HT (n = 17), AMI-NT (n = 17), HT (n = 17), and NT
      (n = 17), we measured resting muscle sympathetic nerve activity (MSNA) as the
      mean frequency of multiunit bursts (m-MSNA) and single units (s-MSNA). In AMI
      groups data were obtained 2 to 4 days after AMI and then at 3-month intervals
      until MSNA returned to levels found in HT and NT. RESULTS: The AMI-HT had greater
      (at least P < 0.05; ANOVA) s-MSNA (99 +/- 3.5 impulses/100 cardiac beats) than
      AMI-NT (84 +/- 2.8 impulses/100 cardiac beats). During follow up, s-MSNA
      hyperactivity in AMI-HT was always greater than in AMI-NT, and returned to values
      found in HT and NT (84 +/- 3.5 impulses/100 cardiac beats and 62 +/- 4.4
      impulses/100 cardiac beats, respectively) 9 months after AMI. Similar results
      were obtained for m-MSNA. CONCLUSIONS: AMI in hypertensives resulted in greater
      MSNA levels lasting at least 6 months longer than AMI in normotensives. This
      indicates that AMI further augmented the MSNA hyperactivity of HT and that this
      could be one mechanism involved in the reported worse prognosis in AMI-HT.

PMID- 17027831
TI  - Reviewer critique of the sympathetic drive after acute myocardial infarction in
      hypertensive patients.

PMID- 17027832
TI  - Antihypertensive agents have different ability to modulate arterial pressure and
      heart rate variability in 2K1C rats.
AB  - We examined the effect of chronic (15 days) administration of antihypertensive
      agents, from different pharmacologic classes, on arterial pressure (AP) and heart
      rate variability in two-kidney, one-clip hypertensive (2K1C) rats. The 2K1C rats
      received by gavage one of the following: water, ramipril, losartan, atenolol,
      amlodipine, or hydrochlorothiazide. Sham-operated normotensive rats received
      water. After 15 days of treatment AP was continuously sampled from an indwelling
      catheter in awake rats during a 2-h period and systolic AP and pulse interval
      (PI) were submitted to autoregressive spectral analysis with oscillatory
      components quantified in low (LF: 0.25 to 0.75 Hz) and high (HF: 0.75 to 3.0 Hz)
      frequency bands. The AP measured by tail-cuff was 170 +/- 2 mm Hg in 2K1C and 131
      +/- 3 mm Hg in normotensive rats. Pooled data indicated that all antihypertensive
      agents reduced the AP of 2K1C rats to 127 +/- 2 mm Hg, whereas 2K1C rats treated
      with water remained hypertensive (206 +/- 11 mm Hg). Variance of systolic AP was
      found increased in 2K1C rats treated with water (34 +/- 2 mm Hg2), whereas 2K1C
      rats treated with ramipril, atenolol, amlodipine, or hydrochlorothiazide
      presented AP variance similar to normotensive rats (16 +/- 2 mm Hg2). Losartan
      normalized AP of 2K1C rats but variance of systolic AP remained increased (34 +/-
      7 mm Hg2). The 2K1C rats treated with water had increased LF of systolic AP,
      whereas 2K1C rats treated with losartan showed higher LF of systolic AP and PI.
      Atenolol presented lower LF and higher HF of PI. In conclusion, losartan
      normalized AP but did not reduce AP variability, suggesting an autonomic
      imbalance characterized by higher sympathetic modulation of the cardiovascular
      system.

PMID- 17027833
TI  - Beta2-adrenoceptor polymorphisms relate to obesity through blunted leptin
      mediated sympathetic activation.
AB  - BACKGROUND: Obesity is a growing public health problem. It has been reported that
      beta2-adrenoceptor polymorphisms are associated with obesity. This study examines
      the associations of beta2-adrenoceptor polymorphism with relationships between
      plasma norepinephrine (NE) and leptin to evaluate further the mechanisms of
      obesity. METHODS: In 329 normotensive (BP <140/90 mm Hg) men with a wide range of
      BMI (17.0 to 36.5 kg/m2), we measured BMI, total body fat mass, waist-to-hip
      ratio (W/H), BP, plasma NE, leptin, and the beta2-(Arg16Gly, Gln27Glu)
      adrenoceptor polymorphisms. The subjects consisted of 206 nonobese (BMI <25
      kg/m2) and 123 overweight or obese (BMI >or=25 kg/m2) men. RESULTS: Overweight or
      obese subjects had a significantly higher frequency of Gly16 and Glu27 alleles
      compared with nonobese subjects. The subjects carrying Gly16 or Glu27 alleles
      regardless of BMI had greater total fat mass, W/H and plasma leptin compared with
      those without the Gly16 or Glu27 alleles, indicating that Gly16 and Glu27 alleles
      of the beta2-adrenoceptor gene are related to obesity and fat mass. Only in the
      nonobese subjects who carried the Gly16 and Glu27 alleles was there a high plasma
      NE level, but similar in overweight or obese subjects. To evaluate leptin
      mediated sympathetic activation, we performed linear regression analyses between
      plasma leptin and NE. In groups with and without the Gly16 or Glu27 alleles,
      plasma leptin correlated with NE, but the slope in the group carrying the Gly16
      or Glu27 allele was significantly lower than that without the Gly16 or Glu27.
      CONCLUSIONS: The findings demonstrate a strong and significant association of the
      Gly16 and Glu27 alleles with obesity. Lower slopes between leptin and NE in the
      subjects carrying these beta2-adrenoceptor polymorphisms indirectly indicate a
      blunted leptin-mediated sympathetic nerve activity. We propose that the beta2
      adrenoceptor polymorphisms related to blunted leptin-mediated sympathetic
      activation offers further proof for the mechanisms of obesity.

PMID- 17027835
TI  - Interactions between melatonin and estrogen in the regulation of blood pressure
      in women.

PMID- 17027836
TI  - Hypertension, diuretics, and uric acid.

PMID- 17027837
TI  - Vectorcardiographic lead systems for the characterization of atrial fibrillation.
AB  - OBJECTIVE: The aim of the study was to design a vectorcardiographic lead system
      dedicated to the analysis of atrial fibrillation (AF). METHODS: Body surface
      potentials during AF were simulated by using a biophysical model of the human
      atria and thorax. The XYZ components of the equivalent dipole were derived from
      the Gabor-Nelson equations. These served as the gold standard while searching for
      an optimal orthogonal lead system for the estimation of the heart vector while
      using a limited number of electrode positions. Six electrode configurations and
      their dedicated transfer matrices were tested by using 10 different episodes of
      simulated AF and 25 different thorax geometries. RESULTS: Root-mean-square-based
      relative estimation error of the vectorcardiogram using the Frank electrodes was
      0.39. An adaptation of 4 of the 9 electrode locations of the standard
      electrocardiogram, with 1 electrode moved to the back, reduced the error to 0.24.
      CONCLUSION: The Frank lead system is suboptimal for estimating the equivalent
      dipole components (VCG) during AF. Alternative electrode configurations should
      include at least 1 electrode on the back.

PMID- 17027838
TI  - ST-segment elevation: a common finding in severe hypercalcemia.

PMID- 17027839
TI  - P-wave and QRS complex measurements in patients undergoing hemodialysis.
AB  - Hemodialysis (HD) has been associated with an increase in the amplitude of QRS
      complexes. Experience in a single patient with multiple measurements has shown
      that HD leads also to augmentation of P-wave amplitude. The objective of this
      investigation was to evaluate electrocardiogram (ECG) changes with HD in a cohort
      of patients undergoing this procedure with particular emphasis on the P-wave and
      QRS complex changes. The sum of amplitudes of P waves (OP) and QRS complexes
      (OQRS) in millimeters in the 12 leads of the ECG, along with a host of other ECG
      parameters, body weight, blood pressure, heart rate, electrolytes, and
      hemoglobin/hematocrit were measured before and immediately after HD in 47
      patients. Hemodialysis resulted in a loss of a mean of 3 kg of weight and an
      increase in the SigmaP, SigmaQRS, mean QRS duration, maximum P-wave duration, and
      P-wave duration measured in lead II, whereas the changes in mean P-wave and
      corrected QT interval durations were not statistically significant. Percentage
      change (Delta%) in SigmaP and SigmaQRS correlated poorly with Delta% in
      electrolytes, hematocrit, blood pressure, heart rate, and weight. Values for
      SigmaP and SigmaQRS vs weight were r = 0.105, P = .48 and r = 0.09, P = .51,
      respectively. The Delta% in SigmaP correlated well with Delta% in SigmaQRS (r =
      0.42, P = .003). Alterations in P-wave amplitudes and duration commensurate with
      the ones affecting the corresponding QRS complexes occur in patients undergoing
      HD and indicate that evaluation of measurements in serial ECGs should take this
      into account. The mechanisms of these phenomena continue to be elusive, and
      whether they represent cardiac and/or extracardiac influences has not as yet been
      unraveled.

PMID- 17027840
TI  - Assessment of QT-measurement accuracy using the 12-lead electrocardiogram derived
      from EASI leads.
AB  - The purpose of the present study is to assess QT-interval measurements from the
      EASI 12-lead electrocardiogram (ECG) as compared with the standard 12-lead ECG.
      The QT interval was automatically determined in simultaneously recorded standard
      and EASI 12-lead ECGs, using a validated wavelet-based delineator. The agreement
      between the 2 sets of measurements was quantified both on a lead-by-lead basis
      and a multilead basis with global definitions of QRS onset and T-wave end. The
      results show that the agreement between QT-interval measurements from the 2 lead
      systems is acceptable, with negligible mean differences and with correlation
      coefficients ranging from 0.91 to 0.98 depending on the lead studied. Although
      the SD shows a clear dependence on the selected lead (ranging from 9.2 to 26.4
      milliseconds), differences are within the accepted tolerances for automatic
      delineation. In a few patients, large differences were found, mainly because of
      changes in morphology present in both lead systems. QT intervals measured by the
      multilead approach were considerably more stable than single-lead measurements
      and resulted in a much better agreement between the 2 lead systems (correlation
      coefficient, 0.98; QT difference, 1.1 +/- 9.8 milliseconds). Thus, the EASI 12
      lead ECG may be used for reliable QT monitoring when the multilead delineation
      approach is adopted.

PMID- 17027841
TI  - Identification and characterisation of the dopamine receptor II from the cat flea
      Ctenocephalides felis (CfDopRII).
AB  - G protein-coupled receptors (GPCRs) represent a protein family with a wide range
      of functions. Approximately 30% of human drug targets are GPCRs, illustrating
      their pharmaceutical relevance. In contrast, the knowledge about invertebrate
      GPCRs is limited and is mainly restricted to model organisms like Drosophila
      melanogaster and Caenorhabditis elegans. Especially in ectoparasites like ticks
      and fleas, only few GPCRs are characterised. From the cat flea Ctenocephalides
      felis, a relevant parasite of cats and dogs, no GPCRs are known so far. Thus, we
      performed a bioinformatic analysis of available insect GPCR sequences from the
      honeybee Apis mellifera, the mosquito Anopheles gambiae, the fruit fly Drosophila
      melanogaster and genomic sequences from insect species. Aim of this analysis was
      the identification of highly conserved GPCRs in order to clone orthologs of these
      candidates from Ctenocephalides felis. It was found that the dopamine receptor
      family revealed highest conservation levels and thus was chosen for further
      characterisation. In this work, the identification, full-length cloning and
      functional expression of the first GPCR from Ctenocephalides felis, the dopamine
      receptor II (CfDopRII), are described.

PMID- 17027842
TI  - Endocrine control of TAG lipase in the fat body of the migratory locust, Locusta
      migratoria.
AB  - Aspects of the role and activation of the enzyme triacylglycerol lipase (TAG
      lipase) in the fat body of the migratory locust Locusta migratoria were
      investigated. TAG lipase is under the hormonal control of the three endogenous
      adipokinetic peptides of the migratory locust, Locmi-AKH-I, Locmi-AKH-II and
      Locmi-AKH-III. Injection of low doses (5-10 pmol) of each peptide causes an
      increase in lipase activity. The activation of lipase is time dependent: an
      elevated activity was recorded 15 min after injection of 10 pmol Locmi-AKH-I and
      maximum activation was reached after 45-60 min. The activation of TAG lipase is
      also dose-dependent. Doses of 2 pmol of each Locmi-AKH had no effect, whereas 5
      pmol caused a significant activation. Maximum activation is reached with a dose
      of 10 pmol. Analogues of the second messengers cAMP (cpt-cAMP) and IP(3) (F
      IP(3)) both activate the enzyme glycogen phosphorylase whereas only cpt-cAMP, but
      not F-IP(3), activates TAG lipase; cpt-cAMP elevates the lipid levels in the
      haemolymph. Activation of lipase is specific to the three endogenous AKH
      peptides: 5 pmol of the endogenous peptide Locmi-HrTH and 10 pmol of corazonin
      failed to activate lipase. High doses of octopamine did not activate lipase nor
      did they elevate the lipid concentration in the haemolymph. TAG lipase is
      stimulated by flight activity but activation is slower than that of glycogen
      phosphorylase: after 30 min of flight or after 5 min of flight plus 1h of
      subsequent rest, activity of TAG lipase is increased, but not immediately after 5
      min of flight. In contrast, glycogen phosphorylase is activated significantly
      after 5 min of flight. These activation patterns of the two enzymes mirror-image
      the concentration of their substrates in the haemolymph: there is a significant
      decrease in the concentration of carbohydrates after 5 min of flight, whereas no
      change of the concentration of lipids can be measured after such short time of
      flight activity; however, a subsequent rest period of 1h is sufficient to
      increase the lipid concentration.

PMID- 17027843
TI  - Anopheles gambiae immune responses to Sephadex beads: involvement of anti
      Plasmodium factors in regulating melanization.
AB  - We have performed a global genome expression analysis of mosquito responses to CM
      25 Sephadex beads and identified 27 regulated immune genes, including several
      anti-Plasmodium factors and other components with likely roles in melanization.
      Silencing of two bead injection responsive genes, TEP1 and LRIM1, which encode
      proteins known to mediate Plasmodium killing, significantly compromised the
      ability to melanize the beads. In contrast, silencing of two Plasmodium
      protective c-type lectins, CTL4 and CTLMA2, did not affect bead melanization.
      This data suggest that the anti-Plasmodium factors have dual functions, as
      determinants of both Plasmodium killing and melanization of the parasite and
      other foreign bodies, while the Plasmodium protective factors are specifically
      utilized by the parasite for evasion of mosquito defense mechanisms.

PMID- 17027844
TI  - Differential usage of two promoters of the Broad-Complex gene in the silkworm,
      Bombyx mori.
AB  - The Broad-Complex gene encodes one of the key regulators of the ecdysone signal
      cascade. We previously isolated part of the genomic DNA and cDNAs of Broad
      Complex in Bombyx mori (BmBR-C). Here, we report structures of the entire genomic
      DNA and 5' untranslated region (5'-UTR) of the cDNAs. BmBR-C was found to span
      about 158 kbp including 13 exons. In the 5'-UTR, additional alternatively spliced
      exons were identified. The 5' ends of the cDNAs were mapped to two different
      positions, the distal promoter (P(dist)) and proximal promoter (P(prox)),
      separated by 86 kbp. Expression from these promoters was controlled
      differentially. Semi-quantitative PCR using cDNAs from the carcass, silk glands
      and fat body revealed that expression from P(prox) was changed moderately and
      expression from P(dist) was weak and constant during the fourth ecdysis. At the
      onset of pupation, expression from P(prox) was suppressed in all tissues, but
      that from P(dist) was induced in the carcass and ASG. In the fat body, expression
      from both promoters increased in the prepupal stage. A combination of promoters
      differing in responsiveness to an ecdysone signal may serve to achieve a complex
      regulation of downstream genes in reply to a simple hormonal signal.

PMID- 17027845
TI  - Purification, characterization and molecular cloning of the major chitinase from
      Tenebrio molitor larval midgut.
AB  - Insect chitinases are involved in degradation of chitin from the exoskeleton
      cuticle or from midgut peritrophic membrane during molts. cDNAs coding for insect
      cuticular and gut chitinases were cloned, but only chitinases from moulting fluid
      were purified and characterized. In this study the major digestive chitinase from
      T. molitor midgut (TmChi) was purified to homogeneity, characterized and
      sequenced after cDNA cloning. TmChi is secreted by midgut epithelial cells, has a
      molecular weight of 44 kDa and is unstable in the presence of midgut proteinases.
      TmChi shows strong substrate inhibition when acting on umbelliferyl-derivatives
      of chitobio- and chitotriosaccharides, but has normal Michaelis kinetics with the
      N-acetylglucosamine derivative as substrate. TmChi has very low activity against
      colloidal chitin, but effectively converts oligosaccharides to shorter fragments.
      The best substrate for TmChi is chitopentaose, with highest k(cat)/K(M) value.
      Sequence analysis and chemical modification experiments showed that the TmChi
      active site contains carboxylic groups and a tryptophane, which are known to be
      important for catalysis in family 18 chitinases. Modification with p
      hidroximercuribenzoate of a cysteine residue, which is exposed after substrate
      binding, leads to complete inactivation of the enzyme. TmChi mRNA encodes a
      signal peptide plus a protein with 37 kDa and high similarity with other insect
      chitinases from family 18. Surprisingly, this gene does not encode the C-terminal
      Ser-Thr-rich connector and chitin-binding domain normally present in chitinases.
      The special features of TmChi probably result from its adaptation to digest
      chitin-rich food without damaging the peritrophic membrane.

PMID- 17027847
TI  - Active ammonia absorption in the midgut of the Tobacco hornworm Manduca sexta L.:
      transport studies and mRNA expression analysis of a Rhesus-like ammonia
      transporter.
AB  - In this study the mid- and hindgut of Manduca sexta larvae were tested for their
      ammonia transport properties using a custom-made Ussing chamber. In the presence
      of 0.1 mmoll(-1) ammonia on both sides of the isolated epithelium, active
      transepithelial ammonia absorption (aTEPA) was observed in all midgut sections,
      with greatest transport rates (ca. 140 nmol cm(-2)h(-1)) detected in the median
      midgut. The hindgut showed no aTEPA. In the median midgut inhibition of energy
      metabolism by azide blocked aTEPA completely, whereas inhibition of vacuolar H(+)
      ATPase by bafilomycin A(1) reduced the active transport by 50%. The imposition of
      a luminal-directed NH(3)-gradient (pH 6.5 apical, pH 8.5 basal) lowered the aTEPA
      by approximately 50% but did not reverse its direction. Apical addition of
      amiloride reduced aTEPA by 90%, suggesting a role of carrier-mediated ammonia
      transport across the apical membrane via a member of the NHE family. Inhibition
      of the microtubule network by colchicine reduced aTEPA by ca. 50%. In contrast,
      blocking basal K(+) channels by Ba(2+) had no effect on aTEPA. Using molecular
      methods, evidence for intestinal expression of a Rhesus-like ammonia transporter
      (RhMS) was found with low mRNA expression in midgut tissues, but high expression
      levels in the hindgut, Malpighian tublules and ganglia.

PMID- 17027846
TI  - Expression and down-regulation of cytochrome P450 genes of the CYP4 family by
      ecdysteroid agonists in Spodoptera littoralis and Drosophila melanogaster.
AB  - The function of CYP4 genes in insects is poorly understood. Some CYP genes are up
      regulated by ecdysteroids and a number of Cyp4 genes in Drosophila melanogaster
      have been shown by microarray to be down-regulated when the ecdysteroid titre is
      high, suggesting hormonal regulation. Here, we report the utilization of certain
      cloned CYP4 cDNAs/fragments to probe their developmental/tissue expression in the
      Lepidopteran, Spodoptera littoralis, including the effects of ecdysteroid
      receptor agonists (bis-acyl hydrazines). CYP4L8 is expressed essentially
      throughout the final larval instar of S. littoralis and, together with CYP4M12,
      is down-regulated by agonist. Furthermore, expression of these genes occurs in
      midgut, but is undetectable in brain, fat body, and integument. Similarly, in D.
      melanogaster, Cyp4ac1, Cyp4ac3, Cyp4ad1 and Cyp4d1 gene expression is drastically
      down-regulated by ecdysteroid agonist. The significance of the results is
      discussed in relation to the plausible functions of the CYP4 genes in Lepidoptera
      and mechanisms of down-regulation.

PMID- 17027848
TI  - Delta11 desaturases of Trichoplusia ni and Spodoptera littoralis exhibit dual
      catalytic behaviour.
AB  - The Delta(11) desaturases found in moths such as Spodoptera littoralis play a
      critical role in the biosynthesis of their sex pheromones. The ability to
      functionally express these enzymes in yeast has allowed one to study the
      transformation of long-chain fatty acyl substrates to their 11-ene products in
      greater mechanistic detail. In this article, we report on the detection and
      quantitation of a minor 11-hydroxylated byproduct (0.1% of total fatty acids),
      which is formed by the Delta(11) desaturases found in Trichoplusia ni and
      Spodoptera littoralis. The position of the hydroxyl group was determined by
      characteristic mass spectral fragmentation of the trimethylsilyl derivatives and
      is in accord with predictions based on previous mechanistic investigations of the
      Spodoptera Delta(11) desaturase. The level of 11-hydroxylation was insensitive to
      the mode of desaturase expression (constitutive vs. induced) and the presence or
      absence of a b5-fusion domain. Our findings suggest that in future, a search for
      hydroxylated products should be included in functional analyses of insect
      desaturase genes.

PMID- 17027849
TI  - New flow cytometric technique for the evaluation of circulating endothelial
      progenitor cell levels in various disease groups.
AB  - Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and
      play a role in vascular repair and re-endothelialisation of injured blood
      vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in
      the general population. It is not clear at present whether and how the numbers of
      circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the
      flow cytometric analysis of whole blood by using a novel cocktail of monoclonal
      antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non
      progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs.
      We analysed 250 patients with varying stages of uraemia, 36 patients with
      inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress
      syndrome and compared this to 74 healthy controls. Using flow cytometry we were
      able to measure the circulating levels of EPCs, with a result available within
      hours of the sample being obtained. Circulating EPC numbers vary in different
      patient groups and healthy controls. In uraemic patients, irrespective of disease
      severity, there are lower numbers of circulating EPC numbers compared to normal
      controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means
      of monitoring patients and shows a reduction in circulating EPCs in uraemic
      patients; this abnormality may be a target of novel therapies.

PMID- 17027850
TI  - Antibody generation through B cell panning on antigen followed by in situ culture
      and direct RT-PCR on cells harvested en masse from antigen-positive wells.
AB  - We describe a method for the generation of high-affinity monoclonal antibodies,
      which combines the power of natural immune responses with in vitro panning, B
      cell culture, RT-PCR and expression of the recombinant product. B cells from
      immunised rabbits were incubated at approximately 1000-10,000 cells per well with
      solid phase antigen coated on the surface of 96-well ELISA plates. Extensive
      washing removed non-binding cells as well as those B cells, which bound with low
      affinity. Retained B cells were cultured for 7 days in the presence of activated
      rabbit splenocyte supernatant and irradiated EL-4-B5 mouse thymoma cells, to
      induce proliferation and secretion of immunoglobulin. Supernatants were screened
      to confirm the presence of specific antibody, before the cells were harvested en
      masse from individual positive wells. Single heavy- and light-chain variable
      region genes were recovered from individual wells by RT-PCR, critically without
      the need for isolation of single B cells. Paired VH and VL genes were
      subsequently expressed as recombinant antibodies and shown to retain the original
      activity and specificity of the B cell culture supernatants. The method has also
      been successfully applied to the generation of high-affinity antibodies to
      antigen expressed on the surface of target cells.

PMID- 17027852
TI  - Dodecin sequesters FAD in closed conformation from the aqueous solution.
AB  - Both extensive theoretical calculations and experimental data obtained during
      several decades leave little doubt that flavin adenine dinucleotide (FAD) exists
      in an open as well as in a closed conformation in aqueous solution. However, the
      knowledge about the intramolecularly stacked complex of FAD is constructed on
      indirect methods while direct structural evidence is lacking. Recently, dodecin
      was reported as an unspecific flavin binding protein which exhibits the unique
      binding mode of incorporating stacked dimers of flavins into a single binding
      pocket. Here, we show that FAD is not bound in this manner, but in monomers of
      intramolecularly stacked conformation. As resulting from the dodecin ligand
      binding characteristic, this FAD stacked conformation suggests to be directly
      sequestered from the aqueous solution and thus to be the first X-ray structural
      view on a FAD solution-stacked form. Moreover, in extraordinary FAD binding,
      dodecin serves as a model for studying bound monomeric (FAD) versus bound dimeric
      (e.g. riboflavin) flavin properties.

PMID- 17027851
TI  - Dyssynchronous (non-uniform) Ca2+ release in myocytes from streptozotocin-induced
      diabetic rats.
AB  - Using biochemical/pharmacological approaches, we previously showed that type 2
      ryanodine receptors (RyR2) become dysfunctional in hearts of streptozotocin
      induced type 1 diabetic rats. However, the functional consequence of this
      observation remains incompletely understood. Here we use laser confocal
      microscopy to investigate whether RyR2 dysfunction during diabetes alters evoked
      and spontaneous Ca(2+) release from the sarcoplasmic reticulum (SR). After 7-8
      weeks of diabetes, steady-state levels of RyR2 remain unchanged in hearts of male
      Sprague-Dawley rats, but the number of functional receptors decreased by >37%.
      Interestingly, residual functional RyR2 from diabetic rat hearts exhibited
      increased sensitivity to Ca(2+) activation (EC(50activation) decreased from 80
      microM to 40 microM, peak Ca(2+) activation decreased from 425 microM to 160
      microM). When field stimulated, intracellular Ca(2+) release in diabetic
      ventricular myocytes was dyssynchronous (non-uniform) and this was independent of
      L-type Ca(2+) currents. Time to peak Ca(2+) increased 3.7-fold. Diabetic myocytes
      also exhibited diastolic Ca(2+) release and 2-fold higher frequency of
      spontaneous Ca(2+) sparks, albeit at a lower amplitude. The amplitude of caffeine
      releasable Ca(2+) was also lower in diabetic myocytes. RyR2 from diabetic rat
      hearts exhibited increased phosphorylation at Ser2809 and contained reduced
      levels of FKBP12.6 (calstablin2). Collectively, these data suggest that RyR2
      becomes leaky during diabetes and this defect may be responsible to the reduced
      SR Ca(2+) load. Diastolic Ca(2+) release could also serve as a substrate for
      delayed after-depolarizations, contributing to the increased incidence of
      arrhythmias and sudden cardiac death in type 1 diabetes.

PMID- 17027853
TI  - In silico approaches reveal the potential for DNA sequence-dependent histone
      octamer affinity to influence chromatin structure in vivo.
AB  - Nucleosome positioning signals embedded within the DNA sequence have the
      potential to influence the detailed structure of the higher-order chromatin
      fibre. In two previous studies of long stretches of DNA, encompassing the chicken
      beta-globin and ovine beta-lactoglobulin genes, respectively, we mapped the
      relative affinity of every site for the core histone octamer. In both cases a
      periodic arrangement of the in vitro positioning sites suggests that they might
      influence the folding of a nucleosome chain into higher-order structure; this
      hypothesis was borne out in the case of the beta-lactoglobulin gene, where the
      distribution of the in vitro positioning sites is related to the positions
      nucleosomes actually occupy in sheep liver cells. Here, we have exploited the in
      vitro nucleosome positioning datasets to simulate nucleosomal organisation using
      in silico approaches. We use the high-resolution, quantitative positioning maps
      to define a one-dimensional positioning energy lattice, which can be populated
      with a defined number of nucleosomes. Monte Carlo techniques are employed to
      simulate the behaviour of the model at equilibrium to produce a set of
      configurations, which provide a probability-based occupancy map. Employing a
      variety of techniques we show that the occupancy maps are a sensitive function of
      the histone octamer density (nucleosome repeat length) and find that a minimal
      change in this property can produce dramatic localised changes in structure.
      Although simulations generally give rise to regular periodic nucleosomal
      arrangements, they often show octamer density-dependent discontinuities, which
      tend to co-localise with sequences that adopt distinctive chromatin structure in
      vivo. Furthermore, the overall organisation of simulated chromatin structures are
      more closely related to the situation in vivo than is the original in vitro
      positioning data, particularly at a nucleosome density corresponding to the in
      vivo state. Although our model is simplified, we argue that it provides a unique
      insight into the influence that DNA sequence can have in determining chromatin
      structure and could serve as a useful basis for the incorporation of other
      parameters.

PMID- 17027854
TI  - Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis.
AB  - PURPOSE: To demonstrate whether optical coherence tomography (OCT-3) and scanning
      laser ophthalmoscopy (HRT-2) can be used to measure changes of the optic disc and
      peripapillary retinal nerve fiber layer (RNFL) in eyes with acute retrobulbar
      optic neuritis that have no clinically apparent optic disc swelling. To correlate
      these findings with presentation magnetic resonance imaging (MRI) of the affected
      optic nerve. METHODS: Eight consecutive patients with acute retrobulbar optic
      neuritis, who had no prior optic neuritis in either eye, were prospectively
      investigated at presentation and at between 1 and 3 months with clinical
      examination, OCT-3, HRT-2. At presentation, MRI of the optic nerves were
      performed in 7/8 patients. RESULTS: Compared to unaffected eyes, affected eyes
      without clinically seen optic disc swelling at baseline, there was a non
      significant trend to increased thickness in the total RNFL, superior and nasal
      measurements. Baseline HRT in affected eyes showed smaller mean cup to disc ratio
      (p=0.003) and a smaller cup area (p=0.002) compared with the unaffected eye. The
      MRI-demonstrated optic nerve lesion did not correlate with OCT RNFL thickening or
      HRT decrease of the physiological cup. Follow-up imaging of the affected eyes
      showed normalization of HRT cup size parameters and OCT RNFL thickness (p<0.04).
      At follow-up, the temporal RNFL had thinning in 7/8 affected eyes (46.8 mum,
      p=0.021) compared with fellow unaffected eyes (57.8 mum), which did not change.
      CONCLUSION: OCT-3 and HRT demonstrate mild RNFL thickening or optic disc swelling
      in acute optic neuritis, even when swelling is not seen clinically. OCT-3 appears
      to reveal measurable RNFL thinning in the temporal quadrant after retrobulbar
      optic neuritis, even though vision improves. RNFL imaging may be useful in future
      studies of residual injury after optic neuritis.

PMID- 17027856
TI  - Myotonic dystrophies type 1 and 2: a summary on current aspects.
AB  - Myotonic dystrophies (DMs) encompass at least 2 forms: myotonic dystrophy type 1
      and 2. In general, DMs are late-onset autosomal dominant disorders characterized
      by a variety of multisystemic features including myotonia, muscular dystrophy,
      cardiac conduction defects, dilated cardiomyopathy, posterior iridescent
      cataracts, frontal balding, insulin-resistance and disease-specific serological
      abnormalities such as gamma-glutamyltransferase and creatine kinase elevations,
      hyperglycemia, hypotestosteronism, and reduced immunoglobulin (Ig) G and IgM
      levels. Beyond the adult forms, in the classic DM1, a congenital form and an
      early-onset form is recognized. Here we summarize current aspects of the myotonic
      dystrophy pathogenesis and review the core features of both types of myotonic
      dystrophies, including the congenital DM1.

PMID- 17027857
TI  - Congenital muscular dystrophies and the extracellular matrix.
AB  - During the past decade, considerable progress in the field of congenital muscular
      dystrophies (CMDs) had led to the identification of a growing number of causative
      genes. This genetic progress has uncovered crucial pathophysiological concepts
      and has been instrumental in redefining clinical phenotypes. Important new
      pathogenic mechanisms include the disorders of O-mannosyl-linked glycosylation of
      alpha-dystroglycan as well as the involvement of a collagen type VI in the
      pathogenesis of congenital disorders of muscle. Thus, an emerging theme among
      gene products involved in the pathogenesis of congenital muscular dystrophy is
      their intimate connection to the extracellular matrix. In this review, we focus
      on the clinical phenotypes that we are correlating with the novel genetic and
      biochemical findings encountered within CMD. This correlation will frequently
      lead to a considerably expanded clinical spectrum associated with a given CMD
      gene.

PMID- 17027858
TI  - Autophagic vacuolar myopathy.
AB  - Autophagic vacuoles are a frequent feature in numerous neuromuscular disorders.
      However, they are also pathognomonic morphologic hallmarks in a slowly emerging
      new group of conditions called autophagic vacuolar myopathies (AVMs), of which
      Danon disease, originally called "lysosomal glycogen storage disease with normal
      acid maltase," is the best known entity. Other such conditions, often although
      not always described from Japan, are X-linked myopathy with excessive authophagy,
      infantile autophagic vacuolar myopathy, adult-onset autophagic vacuolar myopathy
      with multiorgan involvement, and X-linked congenital autophagic vacuolar
      myopathy. Although only 1 protein, the transmembranous lysosomal protein LAMP-2,
      has been found mutated in Danon disease, the remaining AVMs are genetically still
      incompletely identified. Several of these conditions not only share autophagic
      vacuoles, but such autophagic vacuoles also have morphologic properties of the
      sarcolemma, thus rendering them autophagic vacuoles with sarcolemmal features, an
      almost pathognomonic phenomenon of this group of disorders.

PMID- 17027859
TI  - Protein aggregate myopathies.
AB  - Protein aggregate myopathies (PAMs) based on the morphologic phenomenon of
      aggregation of proteins within muscle fibers may occur in children
      (selenoproteinopathies, actinopathies, and myosinopathies) or adults (certain
      myofibrillar myopathies and myosinopathies). They may be mutation related, which
      includes virtually all childhood forms but certain other forms as well, or
      sporadic, which are largely seen in adults. Their classification as myofibrillar
      or desmin-related myopathies, actinopathies, or myosinopathies is based on the
      identification of respective mutant proteins, most of them components of the
      sarcomeres. Recognition of PAM requires muscle biopsy and an extensive
      immunohistochemical and electron microscopic workup of the biopsied muscle tissue
      after which molecular analysis of morphologically ascertained proteins should
      ensue to permit recognition of individual entities and genetic counseling of
      patients and families. Because pathogenetic principles in PAMs are still
      incompletely known, causative therapy, at this time, is not available.

PMID- 17027860
TI  - The childhood limb-girdle muscular dystrophies.
AB  - The heterogeneous childhood limb-girdle muscular dystrophies have originally been
      defined as a group of autosomal recessive and dominant diseases with progressive
      weakness and wasting of shoulder and pelvic-girdle muscles. Over the last 12
      years, the underlying genetic defects for many of the diseases have been
      identified and insight into pathomechanisms of disease has been gained. At the
      same time, improved diagnostic techniques have allowed to extend the phenotypic
      spectrum for many of these devastating conditions, which showed that clinical
      symptoms and pathological findings are not restricted to skeletal muscles.
      Childhood limb-girdle muscular dystrophies are systemic diseases that often
      affect the musculoskeletal, respiratory, and cardiovascular system and that can
      go along with central nervous system involvement and gastrointestinal symptoms.
      The systemic nature of the diseases requires adequate management strategies that
      improve symptoms, longevity, and quality of life of the patients. As we are
      entering an era of translational research the need for precise molecular
      diagnoses, a thorough understanding of the natural history of the diseases and
      guidelines for standardized assessments of the patients become even more
      relevant. In this review, the best characterized childhood limb-girdle muscular
      dystrophies are discussed and their management aspects highlighted.

PMID- 17027861
TI  - Glycogen storage disease: clinical, biochemical, and molecular heterogeneity.
AB  - Glycogen storage diseases (GSDs) are characterized by abnormal inherited glycogen
      metabolism in the liver, muscle, and brain and divided into types 0 to X. GSD
      type I, glucose 6-phosphatase system, has types Ia, Ib, Ic, and Id, glucose 6
      phosphatase, glucose 6-phosphate translocase, pyrophosphate translocase, and
      glucose translocase deficiencies, respectively. GSD type II is caused by
      defective lysosomal alpha-glucosidase (GAA), subdivided into 4 onset forms. GSD
      type III, amylo-1,6-glucosidase deficiency, is subdivided into 6 forms. GSD type
      IV, Andersen disease or amylopectinosis, is caused by deficiency of the glycogen
      branching enzyme in numerous forms. GSD type V, McArdle disease or muscle
      phosphorylase deficiency, is divided into 2 forms. GSD type VI is characterized
      by liver phosphorylase deficiency. GSD type VII, phosphofructokinase deficiency,
      has 2 subtypes. GSD types VIa, VIII, IX, or X are supposedly caused by tissue
      specific phosphorylase kinase deficiency. GSD type 0, glycogen synthase
      deficiency, is divided into 2 subtypes.

PMID- 17027862
TI  - Spinal muscular atrophy: from gene to therapy.
AB  - The molecular basis of spinal muscular atrophy (SMA), an autosomal recessive
      neuromuscular disorder, is the homozygous loss of the survival motor neuron gene
      1 (SMN1). A nearly identical copy of the SMN1 gene, called SMN2, modulates the
      disease severity. The functional difference between both genes is a
      translationally silent mutation that, however, disrupts an exonic splicing
      enhancer causing exon 7 skipping in most SMN2 transcripts. Only 10% of SMN2
      transcripts encode functional full-length protein identical to SMN1.
      Transcriptional activation, facilitation of correct SMN2 splicing, or
      stabilization of the protein are considered as strategies for SMA therapy. Among
      various drugs, histone deacetylase inhibitors such as valproic acid (VPA) or 4
      phenylbutyrate (PBA) have been shown to increase SMN2-derived RNA and protein
      levels. Recently, in vivo activation of the SMN gene was shown in VPA-treated SMA
      patients and carriers. Clinical trials are underway to investigate the effect of
      VPA and PBA on motor function in SMA patients.

PMID- 17027863
TI  - "My son is still walking": stages of receptivity to discussions of advance care
      planning among parents of sons with Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is an inherited progressive neuromuscular disease
      that generally results in death by early adulthood. Because of its life
      threatening nature, discussions of advance care planning are extremely relevant
      to families with affected children and adolescents. Seventeen parents of sons
      with Duchenne muscular dystrophy were interviewed about their attitudes,
      experiences, and the nature of their discussions about these topics. Parents
      showed a lack of familiarity with and experience communicating about advance care
      planning. They also discussed opportunities for communication that centered on
      transitional life events. Parents appeared to vacillate between hope for future
      treatments, avoidance of emotionally difficult aspects of the disease, and
      presence with the fullness of life's experiences. These data suggest a model for
      future research in which windows of opportunity for discussion may exist as sons
      are approaching significant transitional milestones and parents are able to see
      the world through a lens of "presence."

PMID- 17027864
TI  - Anti-leukemic activities of Dictyostelium secondary metabolites: a novel aromatic
      metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from Dictyostelium
      mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells.
AB  - It has previously been shown that DIF-1, a differentiation-inducing factor of the
      cellular slime mold Dictyostelium discoideum, possesses antitumor activities in
      mammalian tumor cells and that neuronal differentiation of PC12 cells can be
      induced with furanodictines (FDs), aminosugar analogs found in D. discoideum, or
      dictyoglucosamines (DGs), N-acetyl glucosamine derivatives (DG-A from D.
      purpureum and DG-B from D. discoideum). Thus, cellular slime molds are attractive
      natural resources that may provide valuable lead compounds to be utilized in the
      field of pharmacology and medicine. In this study, we have isolated a novel
      aromatic compound, 4-methyl-5-n-pentylbenzene-1,3-diol (MPBD), from fruiting
      bodies of the cellular slime mold D. mucoroides and assessed the in vitro
      antiproliferative activities of MPBD, FDs, and DGs in human leukemia K562 and HL
      60 cells. MPBD at 20-80 microM dose-dependently suppressed cell growth in both
      K562 and HL-60 cells. While FDs at 10-80 microM did not affect cell growth, DGs
      at 10-40 microM dose-dependently suppressed cell growth in the cells. Although we
      failed to find the roles of FDs and DGs in the original organisms, MPBD at 5-20
      microM was found to promote stalk cell formation in D. discoideum. The present
      results indicate that MPBD, DGs or their derivatives may have therapeutic
      potential in the treatment of cancer and confirm our expectations regarding
      cellular slime molds as drug resources.

PMID- 17027865
TI  - Acute exposure to UVB has a more profound effect on plant genome stability than
      chronic exposure.
AB  - Environmental factors that damage DNA have various lengths of exposure and
      intensity levels. Although the results of increasing the intensity of a DNA
      damaging agent is often predictable, it is not clear whether the stage during
      development when the exposure is received has any influence on the amount of DNA
      damage. In this paper we analyzed the influence of UVB on the stability of
      Arabidopsis thaliana and the Nicotiana tabacum genomes. Our experiments showed
      that the acute exposure to UVB produces a significantly greater increase in
      homologous recombination frequency (HRF) and recombination rate (RR) compared
      with that produced by chronic exposure. The increase in HRF showed a positive
      correlation with UVB dose and a negative correlation with plant age. In other
      words, as the UVB dose was increased, there was a concomitant increase in HRF.
      Conversely, older plants had a lower HRF increase as compared to younger plants.
      Our experiments suggest that exposure to UVB makes the most significant impact on
      genome stability during the early stages of plant development.

PMID- 17027866
TI  - Amygdala control of emotion-induced forgetting and remembering: evidence from
      Urbach-Wiethe disease.
AB  - When presented in a neutral context, emotional items interfere with episodic
      encoding of temporally contiguous non-emotional items, resulting in dissociable
      valence-dependent retrograde and arousal-dependent anterograde modulatory
      effects. By studying two rare patients with congenital lipoid proteinosis (Urbach
      Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we
      demonstrate that this bidirectional modification of episodic encoding by emotion
      depends on the integrity of the amygdala, as both retrograde and anterograde
      modulatory effects are absent. Our findings implicate the amygdala in a neural
      circuitry that orchestrates rapid retrograde and anterograde regulation of
      episodic memory access upon criteria of behavioral significance.

PMID- 17027867
TI  - Decomposition of extremely hard-to-degrade animal proteins by thermophilic
      bacteria.
AB  - Hard-to-degrade animal proteins are ubiquitously present throughout animal
      bodies. Enormous numbers of these proteins generated in the meat industry are
      converted to industrial wastes, the disposal of which is tremendously difficult.
      Most hard-to-degrade animal proteins are currently disposed of by incineration;
      however, this method has ecological disadvantages in terms of an apparent energy
      loss and the production of a large amount of carbon dioxide. As a result, an
      innovative solution to these problems has been sought. In this review, we focus
      on the degradation of three hard-to-degrade animal proteins (extracellular matrix
      proteins, collagen in particular, keratin, and prion proteins) and discuss the
      decomposing capability of thermophilic bacteria. These proteins are strongly
      resistant to proteinases because of their structural features; therefore, new
      approaches employing bacterial proteases with strong activity and broad
      specificity are required for practical application.

PMID- 17027868
TI  - Purification and characterization of an alkaline lipase from Pseudomonas
      aeruginosa isolated from putrid mineral cutting oil as component of metalworking
      fluid.
AB  - Extracellular lipase was isolated and purified from the culture broth of
      Pseudomonas aeruginosa, an extremophile which naturally grows in water-soluble
      mineral cutting oil (pH 10) used as metalworking fluid (MWF) for cooling and
      lubrication in industrial metalworking processes. The molecular mass of the
      purified lipase was estimated by SDS-PAGE to be 54 kDa. The optimum pH and
      temperature were 11 and 70 degrees C, respectively. The enzyme is stabile over a
      broad pH range (pH 4-11.5). The lipase preferably acted on triacylglycerols with
      medium-chain fatty acids. The lipase was inhibited strongly by Zn(2+), Hg(2+),
      Cu(2+) and slightly by Ca(2+) and Mg(2+). Non-ionic detergents and
      sodiumdeoxycholate enhanced lipase activity. Alkaline lipase from P. aeruginosa,
      capable of growing in a water-restricted medium has excellent properties and good
      potential for biotechnological applications in the metal industry. Its marked
      stability and activity in organic solvents suggest that this lipase is highly
      suitable as a biotechnological tool in a water-restricted medium with a variety
      of applications including organosynthetic reactions and the control and
      prevention of MWF putrification in the metal industry.

PMID- 17027869
TI  - Highly sensitive real-time PCR assay for quantification of toxic cyanobacteria
      based on microcystin synthetase A gene.
AB  - The presence of cyanobacterial bloom in water supply reservoirs can cause
      potential health hazards. In this study, we aimed at the quantification of
      microcystin-producing cyanobacteria based on the microcystin synthetase A (mcyA)
      gene using real-time PCR. To perform a highly sensitive real-time PCR assay, the
      novel primer MSR-2R was designed and a coprecipitation DNA extraction method was
      used in this study. Cyanobacterial cells could be collected efficiently by
      coprecipitation with other bacteria suspended in solution even in the case of low
      concentrations of cyanobacteria. The detection limit of the method was found to
      be 8.8 cells per reaction. When cyanobacterial growth was monitored in pure
      culture, the cell concentration determined by real-time PCR positively correlated
      with the cell concentration determined from direct microscopic count.
      Furthermore, we could detect and quantify the mcyA gene in lake water samples
      using real-time PCR. It was concluded that the quantification of the mcyA gene
      based on real-time PCR is a powerful tool for the rapid quantification of
      microcystin-producing cyanobacteria in environmental samples.

PMID- 17027870
TI  - Effective utilization of transmitted light for astaxanthin production by
      Haematococcus pluvialis.
AB  - A new cultivation method, in which physiological responses of Haematococcus
      pluvialis to different intensities and wavelengths of illuminating light are
      utilized, is proposed. In this method, light transmitted through a cultivation
      vessel illuminated from the opposite side was utilized for the early-phase
      cultivation of H. pluvialis in another inoculated vessel that was located behind
      the cultivation vessel, to save time required for the growth of cells. After
      harvesting cells from the front vessel, the vessel that was originally behind was
      shifted to the position of the front vessel. The abrupt increase in light
      intensity caused by shift of the position induced the effective accumulation of
      astaxanthin. These procedures for inoculation, shift of vessels and harvest were
      repeated using two vessels arranged in series along the light path. After four
      repeated cycles of cultivation (840 h from the start of cultivation), using 2.5
      cm thick vessels, astaxanthin production per unit volume and the astaxanthin
      content were higher than obtained in a batch cultivation with two 2.5 cm vessels.

PMID- 17027871
TI  - High-efficiency secretory production of peroxidase C1a using vesicular transport
      engineering in transgenic tobacco.
AB  - Horseradish peroxidase isozyme C1a (HRP C1a) is widely used as a reporter enzyme
      in a variety of detection procedures such as enzyme-linked immunosorbent assay
      (ELISA) and western blotting. We previously isolated the gene encoding HRP C1a
      and showed that HRP C1a is at first translated as a preproprotein containing
      propeptides at its N- and C-termini (N-terminal secretion signal peptide and C
      terminal propeptide; CTPP). The signal peptide (sp) is necessary for endoplasmic
      reticulum (ER) translocation and the CTPP acts as a vacuolar sorting determinant.
      Furthermore, HRP C1a was secreted into the culture medium from cells expressing
      the HRP C1a gene without the CTPP region. We optimized the secretory production
      system of HRP C1a in tobacco plants. To determine a suitable signal peptide for
      high-efficient secretion of proteins, three types of sp derived from HRP C1a
      (C1Psp), beta-D-glucan exohydrolase (GEsp) and 38 kDa peroxidase (38Psp) were
      compared. GE and 38P are secretory proteins highly accumulated in the culture
      medium of BY2 cells. The secretion efficiency was increased by 34% and 53% when
      GEsp and 38Psp was used, respectively. Next, we used a translational enhancer,
      the 5'-untranslated region of Nicotiana tabacum alcohol dehydrogenase gene (NtADH
      5'-UTR). The production of HRP C1a was increased by placing NtADH 5'UTR in front
      of the ORF in BY2 cells. These results indicate that the localization and
      expression level of recombinant proteins can be controlled by the use of
      propeptides and 5'UTR, respectively. Finally, high-efficiency secretory
      production of the HRP C1a was also achieved in transgenic tobacco.

PMID- 17027872
TI  - Characterization of autoinducer 2 signal in Eikenella corrodens and its role in
      biofilm formation.
AB  - Quorum sensing (QS) is a process by which bacteria communicate using secreted
      chemical signaling molecules called autoinducers (AIs). By this process, many
      bacterial species modulate the expression of a wide variety of physiological
      functions in response to changes in population density. In this study, the
      periodontal pathogen Eikenella corrodens was observed to secrete type 2 signaling
      molecules. An ortholog of luxS, the gene required for AI-2 synthesis in Vibrio
      harveyi, was isolated from the E. corrodens genome. A V. harveyi bioassay showed
      luxS functionality in E. corrodens and the ability of luxS to complement the luxS
      negative phenotype of Escherichia coli DH5alpha. AI activity was detected in the
      supernatant, and the maximum expression of AI-2 was observed during the late
      exponential phase. To determine the potential role of luxS in the colonization
      processes, an E. corrodens luxS mutant was constructed and tested for its
      capacity to form an in vitro biofilm on a polystyrene surface. The biofilm
      forming efficiency of the luxS mutant was approximately 1.3-fold greater than
      that of the wild type. These data suggest that a LuxS-dependent signal plays a
      role in the biofilm formation by E. corrodens.

PMID- 17027873
TI  - Transmission electron microscopic study on supramolecular nanostructures of
      bacteriochlorophyll self-aggregates in chlorosomes of green photosynthetic
      bacteria.
AB  - Supramolecular nanostructures of bacteriochlorophyll (BChl) self-aggregates in
      major light-harvesting complexes (chlorosomes) of green photosynthetic bacteria
      were successfully observed by freeze-fracture transmission electron microscope.
      Rod-shaped nanostructures with approximately 10 nm in diameter could be
      visualized in three types of green sulfur bacteria (Chlorobium). Diameter of the
      rod-shaped nanostructures in Chlorobium chlorosomes was independent of the
      molecular structures of their light-harvesting pigments, namely BChl-c or d. In
      contrast, chlorosomes of the green filamentous bacterium Chloroflexus aurantiacus
      had rod-shaped nanostructures with approximately 5 nm in diameter. The present
      results support that BChl self-aggregates in chlorosomes form rod-shaped
      nanostructures called rod-elements with approximately 10- and 5-nm diameters for
      Chlorobium and Chloroflexus, respectively.

PMID- 17027874
TI  - Isolation and characterization of Streptomyces sp. NL15-2K capable of degrading
      lignin-related aromatic compounds.
AB  - Strain NL15-2K was isolated from soil by screening for bacteria capable of
      catabolizing lignin-related aromatic acids. This isolate was identified as a
      Streptomyces sp. on the basis of morphology and an analysis of its 16S rRNA gene
      sequence. NL15-2K utilized caffeic acid, coniferyl alcohol, ferulic acid,
      isovanillic acid, protocatechuic acid, vanillic acid, vanillin, and veratric acid
      as sole carbon sources.

PMID- 17027876
TI  - Thermotolerant Bacillus licheniformis TY7 produces optically active l-lactic acid
      from kitchen refuse under open condition.
AB  - A thermotolerant l-lactic-acid-producing bacterium was isolated and identified as
      Bacillus licheniformis TY7. TY7 shows optimum growth at pH 6.5 at 30 degrees C
      and normal growth up to 65 degrees C. Using nonsterile kitchen refuse at 50
      degrees C, the strain produced 40 g/ll-lactic acid with 97% optical activity and
      2.5 g/lxh productivity.

PMID- 17027875
TI  - Selection of photosynthetic bacterium Rhodobacter sphaeroides 14F for
      polyhydroxyalkanoate production with two-stage aerobic dark cultivation.
AB  - Polyhydroxyalkanoate (PHA) production abilities in a two-stage aerobic dark
      culture of photosynthetic bacteria were investigated at relatively high
      temperatures (37-40 degrees C). A 14F strain, identified as Rhodobacter
      sphaeroides, showed the highest PHA production (3.5 g/l PHA with 60% PHA
      content). Its productivity was 2-3 times higher than those of other
      photosynthetic bacteria.

PMID- 17027877
TI  - Glucosylation of flavonols by Escherichia coli expressing glucosyltransferase
      from rice (Oryza sativa).
AB  - A glucosyltransferase cDNA, RF5, was cloned from Oryza sativa using an RT-PCR
      strategy and expressed in Escherichia coli. Several flavonoids were tested for
      their ability to serve as substrates for RF5. RF5 effectively glucosylated
      kaempferol and quercetin to produce their 3-O-glucosides. Thus, RF5 could be
      defined as a flavonol 3-O-glucosyltransferase. E. coli cells expressing RF5
      effectively converted 100 microM of kaempferol and quercetin into their
      corresponding glucosides.

PMID- 17027878
TI  - Macrocyclic diarylheptanoids from Garuga pinnata.
AB  - Three macrocyclic diarylheptanoids, 6'-hydroxygaruganin V (1), 9'
      desmethylgarugamblin I (2) and 1,9'-didesmethylgaruganin III (3) were isolated
      from the petroleum ether and dichloromethane extracts of the stem bark of Garuga
      pinnata. The structures of these compounds were established by extensive
      spectroscopic studies, including high field NMR and MS measurements.

PMID- 17027879
TI  - Stereochenols A and B, two quinones from Stereospermum chelonoides.
AB  - Two quinones, stereochenols A (1) and B (2) were isolated from a methanol extract
      of the stem bark of Stereospermum chelonoides, in addition to the known
      naphthoquinones, sterekunthal B (3) and sterequinone C (4). The structures of
      these compounds were established by extensive spectroscopic analyses and by
      comparison of their spectral data with those of related compounds.

PMID- 17027880
TI  - Factors influencing the care needs and demands of rural outpatients in Shaanxi,
      China.

PMID- 17027881
TI  - Influenza vaccination coverage rates in the UK: a comparison of two monitoring
      methods during the 2002-2003 and 2003-2004 seasons.
AB  - OBJECTIVES: To assess the feasibility of measuring influenza vaccination coverage
      during 2002-2003 and 2003-2004 seasons using a telephone survey; to compare these
      findings with routine vaccine uptake monitoring based on data provided by general
      practitioners. STUDY DESIGN: Telephone-based survey. METHODS: We interviewed a
      random sample of non-institutionalized individuals representative of the
      population aged 16 years and over. Four target groups were determined for
      analysis: (1) people aged 65 years and over; (2) healthcare workers; (3) people
      under 65 years with chronic illnesses, which placed them at risk for influenza;
      and (4) a group composed of all three previous groups combined. RESULTS: The
      overall sample consisted of 4054 people (about 2000 per season). Population
      influenza vaccine coverage in the UK increased from 22.3% in 2002-2003 to 24.2%
      in 2003-2004. Vaccine uptake was strongly age dependent, even in people aged 65
      years and over (the ages at which all people are routinely targeted). In both
      seasons, the estimates of vaccine uptake in people aged 65 years and over were
      remarkably consistent with those obtained through routine monitoring. Vaccine
      uptake in healthcare workers was markedly suboptimal. CONCLUSIONS: In the UK, a
      telephone-based system of monitoring influenza vaccine uptake seems robust enough
      to generate data that are comparable with routine vaccine monitoring undertaken
      using data provided by general practitioners. Although such a system cannot
      easily contribute towards monitoring of vaccination at local and regional levels,
      it offers a validated method of estimating vaccine uptake that is independent of
      healthcare workers' time. This may be especially important for a pandemic
      vaccination programme, especially in countries in which healthcare resources are
      scarce, or where the configuration of healthcare services is less conducive to
      internal monitoring than is the case in the UK.

PMID- 17027882
TI  - Preconditioning with low concentration NO attenuates subsequent NO-induced
      apoptosis in vascular smooth muscle cells via HO-1-dependent mitochondrial death
      pathway.
AB  - Nitric oxide (NO) signaling pathways are important in both the maintenance of
      vascular homeostasis and disease progression. Overproduction of NO has been
      associated with ischemia/reperfusion (I/R) injury. Growing evidences suggest that
      NO preconditioning has cytoprotective effects against I/R injury. However, the
      mechanism with which NO mediates these effects remains to be elucidated. The
      purpose of this study was to examine the mechanism of how NO preconditioning
      inhibits subsequent NO-induced apoptosis in vascular smooth muscle cells (VSMC),
      specifically focusing on heme oxygenase-1 (HO-1). According to our data, sodium
      nitroprusside (SNP) increased HO-1 expression in a concentration dependent
      manner. Preconditioning with low concentration SNP (0.3mM) inhibited subsequent
      high concentration SNP (1.5mM)-induced apoptosis, and this effect was reversed by
      the HO-1 inhibitor SnPP. Low concentration SNP-mediated protection involved p38
      kinase inactivation and increased Bcl-2 expression. Furthermore, mitochondrial
      membrane potential was concomitantly increased with decreased expressions of Bax,
      Apaf-1, and activity of caspase-3, which was reversed by SnPP treatment. Our
      results show that low concentration SNP preconditioning suppresses subsequent
      high concentration SNP-induced apoptosis by inhibiting p38 kinase and
      mitochondrial death pathway via HO-1-dependent mechanisms in VSMC.

PMID- 17027884
TI  - Perspectives in multiple sclerosis health care: special focus on the costs of
      multiple sclerosis.
AB  - Brain disorders are amongst the leading causes of disease and disability
      worldwide, accounting for 35% of the burden of all diseases in Europe. Despite
      their enormous personal and national impact the knowledge of the financial and
      economic impression of brain disorders has been relatively little researched.
      Recently it has been estimated that there are nearly 400,000 multiple sclerosis
      (MS) patients in Europe, which is 0.003% of all brain disease patients in the
      continent. In MS economic consequences are predominantly the early loss of work
      capacity and the impact of physical and psychological disabilities in a
      population of young adults, hospitalization during severe disease exacerbations
      and the need for assistance in activities of daily living. In the last decade the
      introduction of new immunomodulatory treatments led to an increase in direct
      costs due to the cost of these drugs, but also led to a more intensive management
      of patients. However, most studies of MS costs were carried out prior to the
      widespread use of newer treatments. In the present study we estimated the
      economic impact of MS in Israel and compared the traditional-vertical management
      model with the integrated-multidisciplinary model of health service delivery
      following the introduction of immunomodulatory treatments. Mean direct health
      cost was 8,554 euros and 5,599 euros in the traditional and integrative models,
      respectively (p<0.01). After 1-year follow-up, full-time employment decreased by
      10% in the traditional model and increased by 17% in the integrated model
      (p<0.05). Analysis of variance demonstrated that the model of service delivery
      explained most of the difference in cost between the two models. Compared to mean
      annual costs in Europe that are estimated at 23,695 euros per case the cost of
      health services in Israel by MS patients is significantly lower. MS represents a
      high economic burden to society. In line with the findings from 15 studies
      published in Europe, we can conclude that studies agree with the following
      findings: a) costs outside the healthcare system, non-medical costs and informal
      care dominate the costs of MS, b) costs increase with increasing severity of the
      disease and c) an integrated service delivery model that is satisfying to
      patients on the one hand and cost effective on the other is to be recommended.

PMID- 17027885
TI  - Peripheral blood gene expression signature mirrors central nervous system
      disease: the model of multiple sclerosis.
AB  - Global gene expression analysis using cDNA microarrays has proven to be a
      sensitive method to gain insight into molecular pathways mediating multiple
      sclerosis (MS) activity and to develop and refine the molecular taxonomy of the
      disease. This method was applied as a tool to investigate molecular heterogeneity
      of MS related gene transcripts in the aim of distinguishing between transcripts
      that trigger disease activity and account for direct genotype-phenotype
      correlation, and those whose expression is altered as a downstream effect of
      other genes. This review summarizes the current state of gene expression
      microarray applications for the study of MS, and specifically emphasizes the
      results of gene expression studies using peripheral blood mononuclear cells
      (PBMC) that were shown to be useful for better understanding of disease related
      pathways, monitoring of therapeutic responses to various drugs and prediction of
      clinical outcome. In the long run it is expected that the information provided by
      cDNA microarrays experiments will allow the determination of key molecular
      players involved in MS pathogenesis, and lead to better management of the disease
      using targeted treatments that will prevent its progression.

PMID- 17027886
TI  - The immune system and happiness.
AB  - Human ability to experience negative and positive emotions has an evolutionary
      perspective and the presence of feelings designed to influence behavior should
      thus be reflected in physiological and immune interactions. The complex
      interactions between the immune system and the central nervous system have been
      studied extensively in schizophrenia and depression. On the other hand, effects
      of positive human emotions, especially happiness, on physiological parameters and
      immunity have received very little attention. Emotions are intimately involved in
      the initiation or progression of cancer, HIV, cardiovascular disease, and
      autoimmune disorders. The specific physiological responses induced by pleasant
      stimuli were recently investigated with the immune and endocrine systems being
      monitored when pleasant stimuli such as odors and emotional pictures were
      presented to subjects. The results revealed that an increase in secretory
      immunoglobulin A and a decrease in salivary cortisol were induced by pleasant
      emotions. The mechanisms by which positive as opposed to negative states are
      instantiated in the brain and interact with the immune system are not yet
      understood. The present review investigates relations among physiological
      measures of affective style, psychological well-being, and immune function. There
      is data to support the hypothesis that individuals characterized by a more
      negative affective style poorly recruit their immune response and may be at risk
      for illness more so than those with a positive affective style. Future research
      is needed to expand our knowledge of the physiological and immune interactions of
      positive emotional states and their beneficial effects on health.

PMID- 17027887
TI  - Thrombin in inflammatory brain diseases.
AB  - Inflammatory brain diseases such as multiple sclerosis (MS) include
      hyperactivation of the coagulation pathway which includes thrombin. In the
      experimental autoimmune encephalomyelitis (EAE) model we have found significantly
      higher levels of thrombin inhibitors which include the very early elevation of
      protease nexin 1. The physiological importance of excess thrombin in neural
      tissue is demonstrated by recent experiments which link thrombin with conduction
      block in the sciatic nerve.

PMID- 17027888
TI  - A model for the comprehensive investigation of a chronic autoimmune disease: the
      multiple sclerosis CLIMB study.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous
      system (CNS) resulting in various disabilities including weakness and imbalance,
      visual abnormalities, changes in cognition, as well as bladder and sexual
      dysfunction. The majority of patients begin with a relapsing-remitting course of
      the disease until eventually there is a progressive decline in disability. With
      FDA-approved disease modifying therapy now given to the majority of MS patients
      early in the course of the disease, the advent of MRI imaging, as well as
      advances in immunology and genetics, the study of MS has entered into an exciting
      era. Natural history studies of untreated patients have provided a guide for
      disease prognosis based on the clinical features of the disease but have limited
      utility in this new era of MS. Major questions are unanswered, including how does
      treatment affect the long-term clinical course of the disease and are there major
      subcategories of the disease with different implications for treatment and
      outcome. Advances in our ability to clinically measure and monitor the disease
      through MRI imaging technology, immunology, and genetic analysis provide the
      opportunity to address these critical questions.

PMID- 17027889
TI  - Neuromyelitis optica - Devic's syndrome, update.
AB  - Neuromyelitis optica of Devic (NMO) is a syndrome which combines transverse
      myelitis and optic neuritis. For many years it was assumed that transverse
      myelitis and optic neuritis should be simultaneous, that optic neuritis should be
      bilateral, and that transverse myelitis must be complete. NMO was considered to
      be very rare. Through the 20th century there was a debate on whether NMO is a
      distinct nosologic entity or a form of MS. In 2005 it is now possible to
      distinguish NMO from MS on the basis of the clinical, imaging, serology and
      immunopathology profile. This distinction is necessary for the implementation of
      adequate treatments, as the relapsing form of the illness carries significant
      morbidity and mortality.

PMID- 17027890
TI  - Novel image processing techniques to better understand white matter disruption in
      multiple sclerosis.
AB  - In Multiple Sclerosis (MS) patients, conventional magnetic resonance imaging
      (MRI) shows a pattern of white matter (WM) disruption but may also overlook some
      WM damage. Diffusion tensor MRI (DT-MRI) can provide important in-vivo
      information about fiber direction that is not provided by conventional MRI. The
      geometry of diffusion tensors can quantitatively characterize the local structure
      in tissues. The integration of both conventional MRI and DT-MRI measures together
      with connectivity-based regional assessment provide a better understanding of the
      nature and the location of WM abnormalities. Image processing and visualization
      techniques have been developed and applied to study conventional MRI and DT-MRI
      of MS patients. These include methods of: Image Segmentation for identifying the
      different areas of the brain as well as to discriminate normal from abnormal WM,
      Computerized Atlases, which include structural information obtained from a set of
      subjects, and Tractographies which can aid in the delineation of WM fiber tracts
      by tracking connected diffusion tensors. These new techniques hold out the
      promise of improving our understanding of WM architecture and its disruption in
      diseases such as MS. In the present study, we review the work that has been done
      in the development of these techniques and illustrate their applications.

PMID- 17027891
TI  - European Working Party on Systemic Lupus Erythematosus: a 15-year report.
AB  - The "European Working Party on Systemic Lupus Erythematosus" was created 15 years
      ago in order to promote research in Europe on the different problems related to
      this disease. Nowadays, more than 50 European centres are collaborating in this
      venture, 9 large multicentre studies are ongoing and 10 workshops have been
      organized.

PMID- 17027892
TI  - Type-I interferons and systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease
      characterized by the production of autoantibodies directed against nuclear
      antigens and chronic inflammation affecting multiple tissues. Complex genetic
      disorders are at the origin of the disease in humans and in SLE-prone mice,
      leading to the escape of auto-reactive B-lymphocytes from central and peripheral
      control checkpoints that operate normally in healthy organisms. Although
      necessary, autoimmune B-cells are not sufficient and additional mechanisms such
      as T-cell help are clearly needed for the disease to occur. The role of type-I
      interferons (type-I IFNs), and in particular IFNalpha, as prominent cofactors for
      SLE was suggested years ago. Leading observations in patients and recent data in
      SLE-prone mice have now established IFNalpha as a major actor in SLE. Several
      systemic clinical symptoms and laboratory findings can indeed be interpreted as
      downstream effects of a high IFNalpha production, and point to this cytokine as a
      link between the expansion of autoimmune B-cells and the stimulation of other
      components of the immune system. Consequently, a vicious circle is established
      with overt immune-cell activation and inflammatory infiltrates culminating in the
      selective destruction of tissue targets, notably the kidney. These notions can
      now be transplanted to the clinic and designate IFNalpha as a new promising
      therapeutic target.

PMID- 17027893
TI  - Transforming growth factor-beta signaling through the Smad proteins: role in
      systemic sclerosis.
AB  - Transforming growth factor-beta (TGF-beta) plays a critical role in the
      development of tissue fibrosis. Its expression is consistently elevated in
      affected organs and correlates with increased extracellular matrix deposition.
      During the last few years, tremendous progress has been made in understanding the
      molecular aspects of intracellular signaling downstream of the TGF-beta
      receptors. In particular, Smad proteins, TGF-beta receptor kinase substrates that
      translocate into the cell nucleus to act as transcription factors, have been
      studied extensively. Their role in the transcriptional regulation of type I
      collagen and other extracellular matrix (ECM) genes expression, and in the
      development of fibrosis is of critical importance because it may lead to novel
      therapeutic strategies for the treatment of these multi-organ tissue reactions to
      injury. Systemic sclerosis (SSc) is a complex autoimmune disease characterized by
      pathological remodelling of connective tissues correlated to the activation of
      TGF-beta/Smad signaling pathway. This review focuses on the mechanisms underlying
      Smad modulation of gene expression and how they relate to fibrotic process.
      Potential implications for the development of therapeutic approaches against
      tissue fibrosis during SSc are discussed.

PMID- 17027894
TI  - Paramyxovirus Sendai virus V protein counteracts innate virus clearance through
      IRF-3 activation, but not via interferon, in mice.
AB  - The present study was undertaken to clarify the role of Sendai virus (SeV) V
      protein, which has been shown to downregulate IFN-beta induction through
      inhibition of IRF-3 activation, in viral pathogenesis. Mice infected with rSeV
      mutants, deficient in V expression or expressing V lacking the C-terminus, had
      several-fold higher IFN activity levels in the lungs than those in wild-type
      virus-infected mice, and the mutant viruses were rapidly excluded from the lung
      from the early phase of infection before induction of acquired immunity. In
      addition, the unique early clearance of the mutants did not occur in IRF-3
      knockout (KO) mice. However, high titers of IFN were detected even in the
      infected KO mice. Furthermore, early clearance of the mutant viruses was also
      observed in IFN signaling-deficient mice, IFN-alpha/beta receptor KO mice and
      STAT1 KO mice. These results indicate that SeV V protein counteracts IRF-3
      mediated innate antiviral immunity for efficient virus replication and
      pathogenesis in mice, but it is not IFN.

PMID- 17027895
TI  - Virion tails of Beet yellows virus: Coordinated assembly by three structural
      proteins.
AB  - Filamentous virions of Beet yellows virus contain a long body formed by a major
      capsid protein and a short tail that is assembled by a minor capsid protein
      (CPm), an Hsp70-homolog (Hsp70h), a 64-kDa protein (p64), and a 20-kDa protein
      (p20). Using mutation analysis and newly developed in planta assays, here we
      investigate the genetic requirements for the tail assembly. We show that the
      inactivation of CPm dramatically reduces incorporation of both Hsp70h and p64.
      Furthermore, inactivation of Hsp70h prevents incorporation of p64 into virions
      and vice versa. Hsp70h and p64 are each required for efficient incorporation of
      CPm. We also show that the tails possessing normal relative amounts of CPm,
      Hsp70h, and p64 can be formed in the absence of the major capsid protein and p20.
      Similar to the tails isolated from the wild-type virions, these mutant tails
      encapsidate the approximately 700 nt-long, 5'-terminal segments of the viral RNA.
      Taken together, our results imply that CPm, Hsp70h and p64 act cooperatively to
      encapsidate a defined region of the closterovirus genome.

PMID- 17027896
TI  - Anisotropic local contrast normalization: the role of stimulus orientation and
      spatial frequency bandwidths in the oblique and horizontal effect perceptual
      anisotropies.
AB  - Visual ability for sine waves and other narrowband stimuli shows an oblique
      effect--worst performance at obliques, best at horizontal and vertical
      orientations. Recently, we have shown that with broadband stimuli (either
      1/f(alpha) visual noise or natural scenes), performance for detecting oriented
      content is worst at horizontal, best at the obliques, and intermediate at
      vertical orientations (a "horizontal effect"). This horizontal effect has been
      explained by a cortical contrast normalization model that is both local (over
      orientation and spatial frequency) and anisotropic (due to a numerical bias of
      neurons with different preferred orientations). Here, the bandwidth of content at
      which an oblique effect or horizontal effect occurs was assessed in two
      suprathreshold matching experiments conducted with 1/f(alpha) noise stimuli
      filtered with a triangle increment function of varied bandwidth (16 levels of
      orientation and spatial frequency bandwidth). The results provided further
      support for the local anisotropic normalization model in that an oblique effect
      was observed when a fairly small range of orientations and high spatial
      frequencies were tested and the horizontal effect was observed for broadband
      increments > or = 20 degrees orientation bandwidth and > or = 1-octave in
      frequency. At intermediate spatial frequency and orientation increment
      bandwidths, a blend of the two anisotropies was observed.

PMID- 17027897
TI  - Centrins, gatekeepers for the light-dependent translocation of transducin through
      the photoreceptor cell connecting cilium.
AB  - Centrins are members of a highly conserved subgroup of the EF-hand superfamily of
      Ca(2+)-binding proteins commonly associated with centrosome-related structures.
      In the retina, centrins are also prominent components of the photoreceptor cell
      ciliary apparatus. Centrin isoforms are differentially localized at the basal
      body and in the lumen of the connecting cilium. All molecular exchanges between
      the inner and outer segments occur through this narrow connecting cilium. Ca(2+)
      activated centrin isoforms bind to the visual heterotrimeric G-protein transducin
      via an interaction with the betagamma-subunit. Ca(2+)-dependent assemblies of
      centrin/G-protein complexes may regulate the transducin movement through the
      connecting cilium. Formation of this complex represents a novel mechanism in
      regulation of translocation of signaling proteins in sensory cells, as well as a
      potential link between molecular trafficking and signal transduction in general.

PMID- 17027898
TI  - Insights into functional aspects of centrins from the structure of N-terminally
      extended mouse centrin 1.
AB  - Centrins are members of the family of Ca(2+)-binding EF-hand proteins. In
      photoreceptor cells, centrin isoform 1 is specifically localized in the non
      motile cilium. This connecting cilium links the light-sensitive outer segment
      with the biosynthetic active inner segment of the photoreceptor cell. All
      intracellular exchanges between these compartments have to occur through this
      cilium. Three-dimensional structures of centrins from diverse organisms are
      known, showing that the EF-hand motifs of the N-terminal domains adopt closed
      conformations, while the C-terminal EF-hand motifs have open conformations. The
      crystal structure of an N-terminally extended mouse centrin 1 (MmCen1-L)
      resembles the overall structure of troponin C in its two Ca(2+) bound form.
      Within the N-terminal extension in MmCen1-L, residues W24 and R25 bind to the C
      terminal domain of centrin 1 in a target-protein-like geometry. Here, we discuss
      this binding mode in connection with putative interaction sites of the target
      protein transducin and the self-assembly of centrins.

PMID- 17027899
TI  - A methyl group at C7 of 11-cis-retinal allows chromophore formation but affects
      rhodopsin activation.
AB  - The newly synthesized 11-cis-7-methylretinal can form an artificial visual
      pigment with kinetic and spectroscopic properties similar to the native pigment
      in the dark-state. However, its photobleaching behavior is altered, showing a
      Meta I-like photoproduct. This behavior reflects a steric constraint imposed by
      the 7-methyl group that affects the conformational change in the binding pocket
      as a result of retinal photoisomerization. Transducin activation is reduced, when
      compared to the native pigment with 11-cis-retinal. Molecular dynamics
      simulations suggest coupling of the C7 methyl group and the beta-ionone ring with
      Met207 in transmembrane helix 5 in agreement with recent experimental results.

PMID- 17027900
TI  - Enantioselective separation and determination of single nonylphenol isomers.
AB  - It has recently become clear that an isomer specific view of technical 4
      nonylphenol (NP) is absolutely necessary for the evaluation of the biological
      behavior of NP, raising additional questions concerning enantiomer specific
      effects. For the first time, in this study enantioselective HPLC was applied to
      enantiomeric separation of chiral NP isomers. A semipreparative separation of two
      NP isomers could be achieved. A GC-MS method has been developed for the
      simultaneous detection of three chiral NP isomers in water samples. Investigation
      of influent and effluent samples from a wastewater treatment plant in Germany
      indicated that enantioselective degradation could occur in the environment. In
      one examined influent, an enantiomer ratio of 1.7 for two different isomers was
      determined.

PMID- 17027901
TI  - High-resolution characterization of antibody fragment/antigen interactions using
      Biacore T100.
AB  - A Biacore T100 optical biosensor was used to characterize the binding kinetics of
      a panel of antigen binding fragments (Fabs) directed against the PcrV protein
      from Pseudomonas aeruginosa. PcrV protein forms part of the type III secretion
      system complex of this opportunistic pathogen. We demonstrate that the biosensor
      response data for each Fab collected from three different surface densities of
      the antigen could be fit globally to a simple 1:1 interaction model. Importantly,
      we found that the Fabs with the slowest dissociation rate provided the best
      protection in cell cytotoxicity studies. To further characterize the Fab
      interactions, binding data were automatically acquired at different temperatures
      and under different buffer conditions. The comprehensive characterization of
      these Fabs shows how Biacore T100 can be used to complement protein therapeutic
      discovery programs from basic research to the selection of therapeutic
      candidates.

PMID- 17027902
TI  - Quantification of defensins by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry.

PMID- 17027903
TI  - Comparative quantification of sphingolipids and analogs in biological samples by
      high-performance liquid chromatography after chloroform extraction.
AB  - Sphingosine 1-phosphate (S1P) is an extra- and intracellular messenger that
      specifically activates five G-protein-coupled cell surface receptors designated
      S1P(1-5). The S1P(1) receptor is particularly important for the maintenance of
      immune surveillance by regulating egress of lymphocytes from thymus and secondary
      lymphoid organs. S1P is generated through phosphorylation of sphingosine which is
      catalyzed by sphingosine kinase types 1 and 2. The immunosuppressant and
      sphingosine analog Fingolimod (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3
      propanediol, FTY720) can also be phosphorylated and induces lymphopenia by
      downregulating cell surface expression of the S1P(1) receptor on lymphocytes. To
      analyze the role of S1P in lymphocyte circulation and distribution we established
      a high-performance-liquid-chromatography-based method for parallel detection and
      quantification of Fingolimod, sphingosine, and dihydrosphingosine together with
      their phosphorylated derivatives Fingolimod-phosphate, S1P, and
      dihydrosphingosine 1-phosphate. Phosphorylated and nonphosphorylated lipids were
      efficiently isolated from biological samples such as cells, tissues, serum,
      plasma, and media by simple chloroform extraction. Fluorescence labeling with 9
      fluorenylmethyl chloroformiate ensured high selectivity and enhanced sensitivity
      for sphingolipid detection. The described method provides an accurate approach to
      investigate phosphorylation, dephosphorylation, hydrolyzation, and
      dehydrolyzation of sphingolipids and analogs. In addition it works independently
      from enzymatic conversions, measuring actual concentrations rather than enzymatic
      activities.

PMID- 17027904
TI  - Proton nuclear magnetic resonance spectroscopic determination of ethanol-induced
      formation of ethyl glucuronide in liver.
AB  - Ethyl glucuronide (ethyl-beta-D-6-glucosiduronic acid, EtG), a unique metabolite
      of ethanol, has received much recent attention as a sensitive and specific
      biological marker of ethanol consumption. Formed in the liver via conjugation of
      ethanol with activated glucuronate, EtG remains detectable in serum, plasma, and
      hair for days after ethanol abuse. Thus far, gas chromatography-mass spectrometry
      and enzyme-linked immunosorbent assays have been developed to detect trace
      quantities of EtG for forensic purposes, but reports of the nuclear magnetic
      resonance (NMR) properties of EtG have been scarce. Herein we present the first
      report of EtG determination using proton NMR spectroscopy. We collected 700-MHz
      proton spectra of liver extracts from rats treated with a 4-day binge ethanol
      protocol (average ethanol dose: 8.6g/kg/day). An unexpected signal (triplet, 1.24
      ppm) appeared in ethanol-treated liver extracts but not in control samples; based
      on chemical shift and multiplicity, we suspected EtG. We observed quantitative
      hydrolysis of the unknown species to ethanol while incubating our samples with
      beta-glucuronidase, confirming that the methyl protons of EtG were responsible
      for the triplet at 1.24 ppm. This study demonstrates that proton NMR spectroscopy
      is capable of detecting EtG and that future NMR-based metabolomic studies may
      encounter this metabolite of ethanol.

PMID- 17027905
TI  - A homemade cytospin apparatus.

PMID- 17027906
TI  - Development of a viologen-based microtiter plate assay for the analysis of
      oxyanion reductase activity: application to the membrane-bound selenate reductase
      from Enterobacter cloacae SLD1a-1.
AB  - The membrane-bound selenate reductase of Enterobacter cloacae SLD1a-1 is purified
      in low yield and has relatively low activity in the pure form compared to that of
      other oxyanion reductases, such as the membrane-bound and periplasmic nitrate
      reductases. A microtiter plate assay based on the original quartz cuvette
      viologen assay of Jones and Garland (R.W. Jones, P.B. Garland, Biochem. J 164
      (1977) 199-211) was developed specifically for analysis of such low-abundant,
      labile oxyanion reductases. The plate assay detects the enzyme-dependent
      reoxidation of reduced methyl viologen spectrophotometrically at 600 nm. The
      assay is quick, uses a minimal sample volume (<5 microl), can simultaneously test
      a range of alternative substrates, and permits activity measurements on multiple
      samples. We demonstrate the accuracy and versatility of the microtiter plate
      assay by application to the kinetic analysis, inhibition, and pH optimization of
      the membrane-bound selenate reductase from E. cloacae SLD1a-1. Results show that
      the membrane-bound selenate reductase has optimum activity at pH approximately 8
      and its active site is able to accommodate larger inhibitory complexes resulting
      in mixed-type inhibition, in the presence of selenate and potassium thiocyanate.

PMID- 17027908
TI  - 23-carboxy-24,25,26,27-tetranorvitamin D3 (calcioic acid) and 24-carboxy-25,26,27
      trinorvitamin D3 (cholacalcioic acid): end products of 25-hydroxyvitamin D3
      metabolism in rat kidney through C-24 oxidation pathway.
AB  - During the past two and half decades the elucidation of the metabolic pathways of
      25OHD(3) and its active metabolite 1alpha,25(OH)(2)D(3) progressed in parallel.
      In spite of many advances in this area of vitamin D research, the unequivocal
      identification of the end products of 25OHD(3) metabolism through C-24 oxidation
      pathway has not been achieved. It is now well established that both 25OHD(3) and
      1alpha,25(OH)(2)D(3) are metabolized through the same C-24 oxidation pathway
      initiated by the enzyme 24-hydroxylase (CYP24A1). Based on the information that
      the end product of 1alpha,25(OH)(2)D(3) metabolism through C-24 oxidation pathway
      is 1alpha-OH-23- COOH-24,25,26,27-tetranor D(3) or calcitroic acid; the
      metabolism of 25OHD(3) into 23-COOH-24,25,26,27-tetranor D(3) has been assumed.
      Furthermore, a previous study indicated 24-COOH-25,26,27-trinor D(3) as a water
      soluble metabolite of 24R,25(OH)(2)D(3) produced in rat kidney homogenates.
      Therefore, 24-COOH-25,26,27-trinor D(3) was also assumed as another end product
      of 25OHD(3) metabolism through C-24 oxidation pathway. We embarked on our present
      study to provide unequivocal proof for these assumptions. We first studied the
      metabolism of 25OHD(3) at low substrate concentration (3x10(-10)M) using [1,2
      (3)H]25OHD(3) as the substrate in the perfused rat kidneys isolated from both
      normal and vitamin D(3) intoxicated rats. A highly polar water soluble
      metabolite, labeled as metabolite X was isolated from the kidney perfusate. The
      amount of metabolite X produced in the kidney of a vitamin D intoxicated rat was
      about seven times higher than that produced in the kidney of a normal rat. We
      then produced metabolite X in a quantity sufficient for its structure
      identification by perfusing kidneys isolated from vitamin D intoxicated rats with
      high substrate concentration of 25OHD(3) (5x10(-6)M). Using the techniques of
      electron impact and thermospray mass spectrometry, we established that the
      metabolite X contained both 23-COOH-24,25,26,27-tetranor D(3) and 24-COOH
      25,26,27-trinor D(3) in a ratio of 4:1. The same metabolite X containing both
      acids in the same ratio of 4:1 was also produced when 24R,25(OH)(2)D(3) was used
      as the starting substrate. Previously, the trivial name of cholacalcioic acid was
      assigned to 24-COOH-25,26,27-trinorvitamin D(3). Using the same guidelines, we
      now assign the trivial name of calcioic acid to 23-COOH-24,25,26,27-tetranor
      D(3). In summary, for the first time our study provides unequivocal evidence to
      indicate that both calcioic and cholacalcioic acids as the end products of
      25OHD(3) metabolism in rat kidney through C-24 oxidation pathway.

PMID- 17027907
TI  - Serum heat shock protein 70 level as a biomarker of exceptional longevity.
AB  - Heat shock proteins are highly conserved proteins that, when produced
      intracellularly, protect stress exposed cells. In contrast, extracellular heat
      shock protein 70 (Hsp70) has been shown to have both protective and deleterious
      effects. In this study, we assessed heat shock protein 70 for its potential role
      in human longevity. Because of the importance of HSP to disease processes,
      cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in
      centenarians and centenarian offspring are different from controls and (2)
      alleles in genes associated with Hsp70 explain these differences. In this cross
      sectional study, we assessed serum Hsp70 levels from participants enrolled in
      either the New England Centenarian Study (NECS) or the Longevity Genes Project
      (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126
      controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic
      frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266
      from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls
      (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79
      spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS
      centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls
      were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70
      level is associated with longevity; however, no genetic associations were found
      with two SNPs within two hsp70 genes.

PMID- 17027909
TI  - Investigation of the role of cytochrome P450 2B4 active site residues in
      substrate metabolism based on crystal structures of the ligand-bound enzyme.
AB  - Based on the X-ray crystal structures of 4-(4-chlorophenyl)imidazole (4-CPI)- and
      bifonazole (BIF)-bound P450 2B4, eight active site mutants at six positions were
      created in an N-terminal modified construct termed 2B4dH and characterized for
      enzyme inhibition and catalysis. I363A showed a >4-fold decrease in differential
      inhibition by BIF and 4-CPI (IC(50,BIF)/IC(50,4-CPI)). F296A, T302A, I363A,
      V367A, and V477A showed a 2-fold decreased k(cat) for 7-ethoxy-4
      trifluoromethylcoumarin O-deethylation, whereas V367A and V477F showed an altered
      K(m). T302A, V367L, and V477A showed >4-fold decrease in total testosterone
      hydroxylation, whereas I363A, V367A, and V477F showed altered stereo- and
      regioselectivity. Interestingly, I363A showed a 150-fold enhanced k(cat)/K(m)
      with testosterone, and yielded a new metabolite. Furthermore, testosterone
      docking into three-dimensional models of selected mutants based on the 4-CPI
      bound structure suggested a re-positioning of residues 363 and 477 to yield
      products. In conclusion, our results suggest that the 4-CPI-bound 2B4dH/H226Y
      crystal structure is an appropriate model for predicting enzyme catalysis.

PMID- 17027910
TI  - Biological and functional responses of in situ bioassays with Chironomus riparius
      larvae to assess river water quality and contamination.
AB  - Single species responses have the potential to measure impacts at earlier stages
      than more traditional methods based in community structure. This study evaluates
      a bioassay with biological (survival, development, growth) and functional (post
      exposure feeding rate) responses of Chironomus riparius larvae to assess water
      quality and contamination in rivers. The bioassay with C. riparius third instar
      larvae was performed, in autumn and spring, in reference sites and in organic and
      metal contaminated sites in Portuguese rivers. Biotic, physical and chemical
      parameters were determined for each site. The relationship between both bioassays
      responses and biotic indices (IBMWP and IASPT) and the physical and chemical
      parameters of respective sites were determined. In general biotic indices were
      able to discriminate between contaminated and not contaminated sites although
      they demonstrated a poor ability to detect low level of metal contamination
      during autumn. IASPT was negatively related to ammonia concentrations in both
      seasons. No significant differences in survival and post-exposure feeding rate
      were found between sites. Development was inhibited in the most metal
      contaminated site during autumn, but pH and ammonia concentrations in water
      accounted for 82% of developmental variation during this season. Growth was
      highly inhibited in the most metal contaminated site during both seasons. In
      autumn, growth was also inhibited in the low metal contaminated site and, during
      this season, pH and Mn and Fe concentrations in water samples accounted for 97%
      of growth variation between sites. The results suggest that in situ bioassay with
      C. riparius larvae using growth as the endpoint is a responsive and suitable tool
      that can be used as bioindicator of metal pollution and to biomonitor water
      quality in metal contaminated rivers.

PMID- 17027911
TI  - Stress reactivity and coping in seasonal and nonseasonal depression.
AB  - Stress, stress reactivity, and coping skill use were examined in individuals with
      seasonal depression, nonseasonal depression, and nondepressed controls. Although
      participants in the two depressed groups reported using more avoidance coping
      strategies than controls, only participants in the seasonal depressed group
      reported using more season-specific coping (i.e., light-related strategies) than
      participants in the nonseasonal depressed and control groups. Individuals in the
      seasonal depressed group also reporting using acceptance coping strategies less
      frequently than individuals in the control group. Only participants in the
      nonseasonal depressed group, however, exhibited greater psychophysiological
      arousal in reaction to a laboratory stressor (i.e., unsolvable anagram task) when
      compared to participants in the seasonal and nondepressed control groups.
      Participants in both depressed groups reported greater impact of negative life
      events during the past 6 months than did controls. Similarities and differences
      in the two types of depression may have implications for the conceptualization
      and treatment of seasonal depression.

PMID- 17027912
TI  - Zuotin, a DnaJ molecular chaperone, stimulates cap-independent translation in
      yeast.
AB  - A small inhibitor RNA (IRNA) isolated from yeast has previously been shown to
      efficiently block poliovirus and hepatitis C virus IRES-mediated translation by
      sequestering mammalian RNA-binding (transacting) factors that play important
      roles in cap-independent translation. Here we have investigated the IRNA-binding
      proteins that might be involved in cap-independent translation in the yeast
      Saccharomyces cerevisiae. We have identified Zuotin, a DnaJ chaperone protein
      similar to mammalian HSP-40 chaperone, which interacts strongly with IRNA. Using
      ZUO1-deleted S. cerevisiae, we demonstrate a preferential requirement of Zuo1p
      for cap-independent translation mediated by the 5' untranslated region of the
      yeast TFIID mRNA. Further studies using zuo1delta S. cerevisiae complemented with
      various Zuo1p mutants indicate that the DnaJ domain of Zuo1p, known to influence
      its interaction with HSP-70, significantly affects cap-independent translation.
      These results demonstrate for the first time a role for an established chaperone
      protein in cap-independent translation of a cellular mRNA.

PMID- 17027913
TI  - Hyaluronidase increases the biodistribution of acid alpha-1,4 glucosidase in the
      muscle of Pompe disease mice: an approach to enhance the efficacy of enzyme
      replacement therapy.
AB  - Pompe disease (glycogen storage disease type II) is a glycogen storage disease
      caused by a deficiency of the lysosomal enzyme, acid maltase/acid alpha-1,4
      glucosidase (GAA). Deficiency of the enzyme leads primarily to intra-lysosomal
      glycogen accumulation, primarily in cardiac and skeletal muscles, due to the
      inability of converting glycogen into glucose. Enzyme replacement therapy (ERT)
      has been applied to replace the deficient enzyme and to restore the lost
      function. However, enhancing the enzyme activity to the muscle following ERT is
      relatively insufficient. In order to enhance GAA activity into the muscle in
      Pompe disease, efficacy of hyaluronidase (hyase) was examined in the heart,
      quadriceps, diaphragm, kidney, and brain of mouse model of Pompe disease.
      Administration of hyase 3000 U/mouse (intravenous) i.v. or i.p. (intraperitoneal)
      and 10 min later recombinant human GAA (rhGAA) 20 mg/kg i.v. showed more GAA
      activity in hyase i.p. injected mice compared to those mice injected with hyase
      via i.v. Injection of low dose of hyase (3000 U/mouse) or high dose of hyase
      (10,000 U/mouse) i.p. and 20 min or 60 min later 20 mg/kg rhGAA i.v. increased
      GAA activity into the heart, diaphragm, kidney, and quadriceps compared to hyase
      untreated mice. These studies suggest that hyase enhances penetration of enzyme
      into the tissues including muscle during ERT and therefore hyase pretreatment may
      be important in treating Pompe disease.

PMID- 17027914
TI  - Identification of two isoforms of Dsk2-related protein XDRP1 in Xenopus eggs.
AB  - The budding yeast UbL-UBA protein Dsk2 has a UbL domain at its N-terminus and a
      UBA domain at its C-terminus, and thus functions as a shuttle protein in the
      ubiquitin-proteasome pathway. In this report we describe two isoforms of Xenopus
      Dsk2-related protein, XDRP1L and XDRP1S. Difference of the two proteins in
      sequence was that the UbL domain of XDRP1S lacks 15 residues in the middle part
      of that of XDRP1L. Both XDRP1L and XDRP1S were expressed in Xenopus eggs. XDRP1L
      and XDRP1S bound to polyubiquitinated proteins via their UBA domains. XDRP1L also
      bound to the proteasome via its UbL domain, whereas the XDRP1S UbL domain was
      less likely to bind to the proteasome. Instead, XDRP1S not XDRP1L bound to
      monomeric cyclin A and prevented its degradation. The existence of such Dsk2
      isoforms in Xenopus eggs suggests that the shuttling function via the UbL-UBA
      protein Dsk2 is evolutionally conserved across species.

PMID- 17027915
TI  - Different expression patterns of TRP genes in murine B and T lymphocytes.
AB  - A prolonged increase in the intracellular calcium concentration ([Ca2+]i) is
      essential for lymphocyte activation that includes cell proliferation and
      differentiation. This increase in [Ca2+]i results from Ca2+ release from the
      intracellular store and the subsequent Ca2+ influx from the extracellular
      environment via calcium channels located on the plasma membrane. Although
      transient receptor potential (TRP) channels have been reported to play important
      roles in the [Ca2+]i increase in lymphocytes, the function of these channels in
      lymphocyte activation remains unknown. Here, we report the comprehensive
      expression profile of TRP channel gene families including TRPC, TRPV, and TRPM in
      the murine immune system. RT-PCR analysis revealed different expression patterns
      of the TRP channel genes in B and T lymphocytes isolated from the spleen.
      Therefore, our results provide an appropriate reference of TRP gene expression in
      murine lymphocytes.

PMID- 17027916
TI  - Isoproterenol suppresses cytokine-induced RANTES secretion in human lung
      epithelial cells through the inhibition of c-jun N-terminal kinase pathway.
AB  - It has been reported that beta2-agonists may potentially exert some anti
      inflammatory action in addition to bronchodilation that may contribute to their
      beneficial effects on asthma control. Bronchial epithelial cells are well known
      to respond to a range of stimuli by producing various biologically active
      mediators that can influence airway inflammation. RANTES (regulated on
      activation, normal T cells expressed and secreted) plays an important role in the
      pathophysiology of airway inflammation of asthmatics through its chemotactic
      activity for eosinophils. In this study, the authors investigated whether
      cytokine-induced RANTES release from BEAS-2B human bronchial epithelial cells
      could be modulated by beta-agonist isoproterenol (ISO). The possible involvement
      of c-jun N-terminal kinase (JNK) pathway was also studied. Combination of tumor
      necrosis factor-alpha and interleukin-1beta (cytokine mix) increased RANTES
      release from BEAS-2B cells and stimulated JNK activity. Similar to JNK inhibitor
      SP600125, ISO inhibited not only the production of RANTES but also the activation
      of JNK pathway in cytokine mix-stimulated BEAS-2B cells. The effect of ISO was
      mediated by the beta2-adrenoceptor, since it was blocked by ICI 118,551, a
      selective beta2-receptor antagonist, but not by atenolol, a selective beta1
      receptor antagonist. Adenylyl cyclase activator forskolin reproduced the effects
      of ISO. Isoproterenol was found to inhibit the release of RANTES from the human
      bronchial epithelial cells, at least in part, through the inhibition of JNK
      signaling pathway.

PMID- 17027917
TI  - Necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and
      TLR3: implication in Wallerian degeneration.
AB  - Schwann cells play an important role in peripheral nerve regeneration. Upon nerve
      injury, Schwann cells are activated and produce various proinflammatory cytokines
      and chemokines, resulting in the recruitment of macrophages and the phagocytosis
      of myelin debris. However, it is unclear how nerve injury induces Schwann cell
      activation. Recently, it was reported that necrotic cells induce immune cell
      activation via toll-like receptors (TLRs). This suggests that the TLRs expressed
      on Schwann cells may recognize nerve injury by binding to the endogenous ligands
      secreted by the damaged nerve, thereby inducing Schwann cell activation. To
      explore such a possibility, we stimulated rat Schwann cells with necrotic
      neuronal cells (NNC). The stimulation of Schwann cells with NNC induced the
      expression of various inflammatory mediators, including TNF-alpha and iNOS.
      Studies on the NNC-mediated intracellular signaling pathways revealed that p38
      and JNK are involved in the NNC-mediated Schwann cell activation. In addition,
      NNC-induced proinflammatory gene expression was reduced in mouse Schwann cells
      derived from TLR2 or TLR3 knockout mice. In summary, these results suggest that
      necrotic neuronal cells induce inflammatory Schwann cell activation via TLR2 and
      TLR3, which might be involved in Wallerian degeneration upon peripheral nerve
      injury.

PMID- 17027918
TI  - Trafficking defect of mutant kidney anion exchanger 1 (kAE1) proteins associated
      with distal renal tubular acidosis and Southeast Asian ovalocytosis.
AB  - Compound heterozygous anion exchanger 1 (AE1) SAO/G701D mutations result in
      distal renal tubular acidosis with Southeast Asian ovalocytosis. Interaction,
      trafficking and localization of wild-type and mutant (SAO and G701D) kAE1
      proteins fused with hemagglutinin, six-histidine, Myc, or green fluorescence
      protein (GFP) were examined in human embryonic kidney (HEK) 293 cells. When
      individually expressed, wild-type kAE1 was localized at cell surface while mutant
      kAE1 SAO and G701D were intracellularly retained. When co-expressed, wild-type
      kAE1 could form heterodimer with kAE1 SAO or kAE1 G701D and could rescue mutant
      kAE1 proteins to express on the cell surface. Co-expression of kAE1 SAO and kAE1
      G701D also resulted in heterodimer formation but intracellular retention without
      cell surface expression, suggesting their trafficking defect and failure to
      rescue each other to the plasma membrane, most likely the molecular mechanism of
      the disease in the compound heterozygous condition.

PMID- 17027919
TI  - MRSP1, encoding a novel Trichoderma secreted protein, is negatively regulated by
      MAPK.
AB  - A novel gene, MRSP1 (MAP kinase repressed secreted protein 1) is strongly
      overexpressed in the tmkA MAPK mutant of the biocontrol fungus Trichoderma
      virens. Transcriptional regulation of MRSP1 is determined by presence or absence
      of TmkA, rather than by light or sporulation, making it a molecular marker for
      the unusual, negative, regulation by TmkA. The predicted protein is 15.9 kDa, has
      a secretory signal, and the four-cysteine pattern, C-X29-CP(G)C-X31-C, may define
      a new cysteine-rich motif. This is a novel protein with functions not known from
      any other organism. Conservation in ascomycete, basidiomycete, and Dictyostelium
      homologs, as well as tight MAPK regulation, might indicate important cellular
      functions.

PMID- 17027920
TI  - Lipid fluidity at different regions in LDL and HDL of beta-thalassemia/Hb E
      patients.
AB  - Atherosclerosis-related vascular complications in beta-thalassemia/hemoglobin E
      (beta-thal/Hb E) patients may result from iron induced oxidation of lipoproteins.
      To identify the specific site of oxidative damage, changes in lipid fluidity at
      different regions in LDL and HDL particle were investigated using two
      fluorescence probes and two ESR spin probes. The magnitude of increased lipid
      fluidity in thalassemic lipoproteins was dependent on the location of the probes.
      In hydrophobic region, the rotational correlation times for 16-doxyl stearic acid
      and DPH anisotropy were markedly changed in LDL and HDL of the patients. In the
      surface region, there was only a slight change in the order parameter (S) for 5
      doxyl stearic acid and TMA-DPH anisotropy. Lipid fluidity at the core of LDL and
      HDL showed good correlation with oxidative stress markers, the ratio of CL/CO,
      and the level of alpha-tocopherol, suggesting that hydrophobic region of
      thalassemic lipoprotein was a target site for oxidative damage.

PMID- 17027921
TI  - Quantitative measurement of damage caused by 1064-nm wavelength optical trapping
      of Escherichia coli cells using on-chip single cell cultivation system.
AB  - We quantitatively examined the possible damage to the growth and cell division
      ability of Escherichia coli caused by 1064-nm optical trapping. Using the
      synchronous behavior of two sister E. coli cells, the growth and interdivision
      times between those two cells, one of which was trapped by optical tweezers, the
      other was not irradiated, were compared using an on-chip single cell cultivation
      system. Cell growth stopped during the optical trapping period, even with the
      smallest irradiated power on the trapped cells. Moreover, the damage to the
      cell's growth and interdivision period was proportional to the total irradiated
      energy (work) on the cell, i.e., irradiation time multiplied by irradiation
      power. The division ability was more easily affected by a smaller energy, 0.36 J,
      which was 30% smaller than the energy that adversely affected growth, 0.54 J. The
      results indicate that the damage caused by optical trapping can be estimated from
      the total energy applied to cells, and furthermore, that the use of optical
      trapping for manipulating cells might cause damage to cell division and growth
      mechanisms, even at wavelengths under 1064 nm, if the total irradiation energy is
      excessive.

PMID- 17027922
TI  - mBET3 is required for the organization of the TRAPP complexes.
AB  - Large tethering complexes mediate the initial interaction of a transport vesicle
      with its target membrane. There are two forms of the multi-subunit tethering
      complex called TRAPP (TRAPPI and TRAPPII) that tether transport vesicles in
      different trafficking steps. Understanding TRAPP complex assembly and the protein
      protein interactions among the subunits is an important step in elucidating the
      function of this tether. Here we have used several different approaches to study
      the protein-protein interactions among the subunits of the TRAPP complexes in
      both mammalian cells and yeast. Our studies have revealed that the low molecular
      weight subunits of TRAPP form two subcomplexes in vitro. One subcomplex contains
      mammalian BET3 (mBET3), mTRS31 and mTRS20, while mBET5 and mTRS23 form a second
      subcomplex. Furthermore, mBET3 directly interacts with mBET5 in vitro. Our
      findings also suggest that the TRAPPII-specific subunit, yTrs120p (yeast
      Trs120p), binds to the periphery of the TRAPPII complex. Although the non
      essential TRAPP subunit yTrs33p interacts with yBet3p, yTrs33p is not required
      for TRAPP complex assembly. Together our findings indicate that BET3 plays an
      important role in the organization of the TRAPP complexes in both mammalian cells
      and yeast.

PMID- 17027923
TI  - Identification and analysis of the mouse basic/Helix-Loop-Helix transcription
      factor family.
AB  - The basic/Helix-Loop-Helix (bHLH) proteins are a family of transcription factors
      that regulates a variety of biological processes. Based on a previously defined
      consensus motif, we identified the complete set of bHLH protein family from the
      mouse proteome databases and carried out a series of bioinformatics analysis. As
      results, 124 mouse bHLH proteins were identified in this study, and 28 of them
      were additional bHLH proteins beyond the previous report. These 124 mouse bHLH
      proteins were classified into groups from A to F by the nomenclature and
      phylogenetic analysis. Statistic analysis of the Gene Ontology annotation of
      these proteins showed that the bHLH proteins tend to perform functions related to
      cell differentiation and development. Gene function enrichment analysis among six
      groups illuminated that the proteins in certain group tend to have special
      biology functions, so that the molecular function of the uncharacterized proteins
      in groups could be inferred.

PMID- 17027924
TI  - Fucoidan prevents C epsilon germline transcription and NFkappaB p52 translocation
      for IgE production in B cells.
AB  - Fucoidan, a dietary fiber contained in seaweed, reduces the increase of antigen
      specific IgE in mice exposed to ovalbumin. In this study, we investigated the
      effect of fucoidan on IgE production and intracellular events in B cells in
      vitro. Fucoidan inhibited the production of IgE and C epsilon germline
      transcription in murine B cells induced by IL-4 (100 ng/ml) and anti-CD40
      antibodies (10 microg/ml), whereas it stimulated cell proliferation. A
      significant effect of fucoidan on IgE production was observed when B cells were
      stimulated with a higher dose (5 microg/ml) of anti-CD40 antibodies, but not when
      stimulated with lower doses (1.25, 2.5 microg/ml), regardless of the IL-4
      concentrations. Moreover, nuclear translocation of NFkappaB p52, but neither that
      of NFkappaB p65, nor the phosphorylation of JAK1 and STAT6 was reduced by
      fucoidan. These results suggest that fucoidan inhibited IgE production by
      preventing the NFkappaB p52-mediated pathways activated by CD40.

PMID- 17027925
TI  - A Cdc2-sensitive interaction of the UbL domain of XDRP1S with cyclin B mediates
      the degradation of cyclin B in Xenopus egg extracts.
AB  - The yeast UbL-UBA protein Dsk2 is thought to act as a shuttle protein that
      delivers polyubiquitinated proteins to the proteasome. Previously, we identified
      Xenopus Dsk2-related protein, XDRP1, as a cyclin A-interacting protein. Using
      Xenopus egg extracts, we further characterized its two isoforms, XDRP1L and
      XDRP1S, with respect to cyclin binding and its degradation. Polyubiquitinated
      cyclins bound to the UBA domain of XDRP1L and XDRP1S, whereas monomeric cyclins A
      and B bound to the UbL domain of XDRP1S but not to XDRP1L. Binding of XDRP1S with
      monomeric cyclins was affected by a Cdc2-mediated phosphorylation of either the
      XDRP1S UbL domain or cyclins. Degradation of cyclin B was also prevented by
      XDRP1S in a Cdc2-sensitive manner. Loss of the XDRP1S-cyclin interaction allowed
      cyclins to be degraded in calcium-treated CSF extracts. These results suggest
      that the shuttling pathway via the UbL-UBA protein XDRP1 participates in
      degradation of mitotic cyclins in Xenopus eggs.

PMID- 17027927
TI  - Neural circuits containing pallidotegmental GABAergic neurons are involved in the
      prepulse inhibition of the startle reflex in mice.
AB  - BACKGROUND: Prepulse inhibition (PPI) of the startle response is a measure of the
      inhibitory function and time-linked information processing by which a weak
      sensory stimulus (the prepulse) inhibits the startle response caused by a sudden
      intense stimulus. We attempted to clarify the neuronal circuits underlying the
      control of PPI of the startle reflex in mice. METHODS: c-Fos immunohistochemistry
      was used to detect neurons activated by startle pulse and/or prepulse trials.
      Behavioural pharmacology and tracing studies were also conducted. RESULTS: The
      lateral globus pallidus (LGP) was activated by prepulses. Activation of the
      caudal pontine reticular nucleus (PnC) evoked by the startle pulses was inhibited
      under PPI conditions. Double-immunostaining revealed that c-Fos-positive cells in
      the LGP following prepulse trials were GABAergic neurons. Bilateral
      microinjections of lidocaine into the LGP resulted in an impairment of PPI.
      Fluoro-gold infusion into the PnC and the pedunculopontine tegmental nucleus
      (PPTg) retrogradely labeled neurons in the PPTg and LGP, respectively.
      Microinjections of phaclofen into the PPTg significantly impaired PPI.
      CONCLUSIONS: These results suggest that GABAergic neurons in the LGP which
      project to the PPTg play a crucial role through the activation of GABAB receptors
      in the regulation of PPI of the startle reflex in mice.

PMID- 17027928
TI  - Voxel-based study of structural changes in first-episode patients with bipolar
      disorder.
AB  - BACKGROUND: Although morphometric studies of bipolar disorder (BD) suggest that
      neurofunctional abnormalities reflect underlying structural changes, it remains
      unclear whether abnormalities are present at illness onset or reflect disease
      progression. Previous voxel-based morphometry (VBM) findings suggest that
      ventrolateral prefrontal cortex (VLPFC) changes develop over time, whereas
      morphologic abnormalities elsewhere in the anterior limbic network (ALN) are
      present early in BD. In this study, we used VBM to explore structural brain
      changes in first-episode bipolar patients. METHODS: First-episode bipolar (n =
      33) and healthy (n = 33) subjects underwent magnetic resonance imaging. Images
      were normalized and compared on a voxel-by-voxel basis. RESULTS: Bipolar subjects
      showed no change in VLPFC density or volume. We observed increased volume in left
      thalamus and fusiform and cerebellum bilaterally; increased gray matter density
      in anterior cingulate and posterior parietal structures; and increased gray
      matter volume and density in middle/superior temporal and posterior cingulate
      gyri. No areas of decreased volume or density were observed. CONCLUSIONS: These
      data indicate that structural changes are absent from VLPFC early in the course
      of BD. Morphologic abnormalities are present in other portions of the ALN and in
      structures previously observed to mediate neurofunctional changes in BD,
      suggesting that dysfunctional neuronal proliferation or pruning may occur in
      bipolar patients.

PMID- 17027929
TI  - Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling
      pairs from the OCD Collaborative Genetics Study.
AB  - BACKGROUND: Identification of familial, more homogenous characteristics of
      obsessive-compulsive disorder (OCD) may help to define relevant subtypes and
      increase the power of genetic and neurobiological studies of OCD. While factor
      analytic studies have found consistent, clinically meaningful OCD symptom
      dimensions, there have been only limited attempts to evaluate the familiality and
      potential genetic basis of such dimensions. METHODS: Four hundred eighteen
      sibling pairs with OCD were evaluated using the Structured Clinical Interview for
      DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist
      and Severity scales. RESULTS: After controlling for sex, age, and age of onset,
      robust sib-sib intraclass correlations were found for two of the four YBOCS
      factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I
      (aggressive, sexual, and religious obsessions, and checking compulsions; p =
      .002). Smaller, but still significant, familiality was found for Factor III
      (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p =
      .04). Limiting the sample to female subjects more than doubled the familiality
      estimates for Factor II (p = .003). Among potentially relevant comorbid
      conditions for genetic studies, bipolar I/II and major depressive disorder were
      strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence,
      and bulimia were associated with Factor II (p < .01). CONCLUSIONS: Factor
      analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some
      gender-dependence, exhibit relatively specific relationships to comorbid
      psychiatric disorders and thus may be useful as refined phenotypes for molecular
      genetic studies of OCD.

PMID- 17027930
TI  - Regional cerebral glucose metabolic abnormalities in bipolar II depression.
AB  - BACKGROUND: Functional neuroimaging studies of bipolar disorder (BD) performed in
      conjunction with antidepressant treatment trials generally require that patients
      remain on mood stabilizers to reduce the risk of inducing mania; yet, it is
      unknown whether the metabolic abnormalities evident in unmedicated BD depressives
      remain detectable in patients receiving mood stabilizers. This study investigated
      whether cerebral metabolic abnormalities previously reported in unmedicated BD
      subjects are evident in depressed bipolar disorder type II (BD II) subjects
      receiving lithium or divalproex. METHODS: Using [18F]-fluorodeoxyglucose-positron
      emission tomography, cerebral glucose metabolism was compared between 13
      depressed BD II subjects on therapeutic doses of lithium or divalproex and 18
      healthy control subjects. Regional metabolism was compared between groups in
      predefined regions of interest. RESULTS: Metabolism was increased in the
      bilateral amygdala, accumbens area, and anteroventral putamen, left orbitofrontal
      cortex and right pregenual anterior cingulate cortex in depressives versus
      control subjects. Post hoc exploratory analysis additionally revealed increased
      metabolism in left parahippocampal, posterior cingulate, and right anterior
      insular cortices in depressives versus control subjects. Correlational analyses
      showed multiple limbic-cortical-striatal interactions in the BD sample not
      evident in the control sample, permitting sensitive and specific classification
      of subjects by discriminant analysis. CONCLUSIONS: These results confirm previous
      reports that bipolar depression is associated with abnormally increased
      metabolism in the amygdala, ventral striatum, orbitofrontal cortex, anterior
      cingulate, and anterior insula, and extend these results to bipolar disorder type
      II depressives on lithium or divalproex. They also implicate an extended
      functional anatomical network known to modulate visceromotor function in the
      pathophysiology of BD II depression.

PMID- 17027931
TI  - Increased amygdala and decreased dorsolateral prefrontal BOLD responses in
      unipolar depression: related and independent features.
AB  - BACKGROUND: Major depressive disorder is characterized by increased and sustained
      emotional reactivity, which has been linked to sustained amygdala activity. It is
      also characterized by disruptions in executive control, linked to abnormal
      dorsolateral prefrontal cortex (DLPFC) function. These mechanisms have been
      hypothesized to interact in depression. This study explored relationships between
      amygdala and DLPFC activity during emotional and cognitive information processing
      in unipolar depression. METHOD: Twenty-seven unmedicated patients with DSM-IV
      unipolar major depressive disorder and 25 never-depressed healthy control
      subjects completed tasks requiring executive control (digit sorting) and
      emotional information processing (personal relevance rating of words) during
      event-related functional magnetic resonance imaging (fMRI) assessment. RESULTS:
      Relative to control subjects, depressed subjects displayed sustained amygdala
      reactivity on the emotional tasks and decreased DLPFC activity on the digit
      sorting task. Decreased relationships between the time-series of amygdala and
      DLPFC activity were observed within tasks in depression, but different depressed
      individuals showed each type of bias. CONCLUSIONS: Depression is associated with
      increased limbic activity in response to emotional information processing and
      decreased DLPFC activity in response to cognitive tasks though these may reflect
      separate mechanisms. Depressed individuals also display decreased relationships
      between amygdala and DLPFC activity, potentially signifying decreased functional
      relationships among these structures.

PMID- 17027932
TI  - Beliefs and interest in cancer risk in an underserved Latino cohort.
AB  - OBJECTIVE: To measure beliefs about cancer causation, cancer screening behaviors,
      access to information about and resources for cancer screening, and interest in
      cancer genetics services in two underserved predominantly Latino communities.
      METHODS: An anonymous survey, in both English and Spanish, was distributed at the
      registration desk to all attendees of selected general medicine clinics in two
      underserved healthcare systems. RESULTS: There were a total of 312 respondents,
      representing 98% of eligible candidates. The reported data focus on 75.3% (n=235)
      of Latino respondents; mean age 43 years; 78% female; 72% less than high school
      education. Heredity was perceived as the most frequent cause of cancer, after
      smoking. Only 37% knew of free cancer screening programs. Over 85% expressed
      interest in obtaining information about personal cancer risk and motivation to
      participate in cancer genetics services. CONCLUSIONS: The results of this survey
      demonstrate an awareness of heredity as a potential cause of cancer. The observed
      high level of interest in cancer genetics services suggests the acceptability of
      cancer genetics services in this predominantly underserved Latino population.
      Furthermore, cancer genetics services would likely augment awareness and
      utilization of available cancer screening services in the community.

PMID- 17027933
TI  - Phonemic restoration in a sentence context: evidence from early and late ERP
      effects.
AB  - When a particular speech sound is obliterated and replaced by a non-speech sound
      in continuous speech the listener may not notice any disturbance in speech or
      have difficulties in understanding the word. The present study examined for the
      first time neurophysiological correlates of the perception of words with an
      obliterated initial phoneme. Behavioral responses and event-related potentials
      (ERPs) were measured while participants listened to naturally spoken sentences
      which had a highly or less expected final word. Half of the sentences were
      manipulated to have a cough replacing the beginning of the final word, thus,
      reducing the initial phonetic information available for the word recognition. An
      N1-P2 complex indicated an automatic registration of the cough's onset. An early
      negativity to less expected relative to highly expected words was observed for
      phonetically intact words but not for manipulated words. Although the N400 effect
      to manipulated words was elicited later than to intact words, after the fragment
      onset, its amplitude was not enhanced. Further, no significant enhancement of the
      N400 was found for the manipulated highly expected words. This finding, together
      with behavioral results, indicated an easier integration of the manipulated
      highly expected words with the sentence context than of intact but less expected
      words. Taken together, the study demonstrates an efficient usage of both a
      context-driven expectancy of the suitable word as well as a stimulus-driven
      processing of the phonetic information during online perception of speech. The
      present ERP results support the earlier behavioral research in showing that
      phonemic restoration is not a bottom-up phenomenon but rather reflects a top-down
      repair process.

PMID- 17027935
TI  - Correcting for false alarms in a simple reaction time task.
AB  - Simple reaction times (RTs) constitute an important source of information and
      tool in human and animal psychophysics, in cognitive neuroscience, and in the
      clinic. We measure simple RTs to auditory stimuli, in a high signal rate
      vigilance design, to examine the possibility that simple RT may be used as a tool
      to study mechanisms of temporal summation at absolute threshold. By means of
      catch trials, we monitor the subjects' tendencies to produce false alarms, that
      is reactions not controlled by the reaction stimulus. Here we examine the
      possibility that a model of a race between a stimulus-controlled reaction process
      and a false alarm process can account for the numbers as well as for the timing
      of early and late RTs on stimulus trials in our experiments. We show that the
      responses in both tails of our empirical RT distributions on stimulus trials are
      indeed correctly predicted by the race model and can be considered false alarms.
      This suggests that the race model might also provide a reasonable description of
      the way in which false alarms and stimulus-controlled reactions combine when they
      overlap in time. We examine the magnitudes of the estimated effects of false
      alarms on several parameters of the RT distributions by application of the race
      model. The analyses reveal that the effects not only vary with false alarm rate
      but also with stimulus parameters. Our data suggest that the race model may
      provide a theoretically reasonable and easy means of correcting for false alarms
      in simple RT paradigms and thus may constitute a useful alternative to the common
      practice of truncation.

PMID- 17027934
TI  - MCH-containing neurons in the hypothalamus of the cat: searching for a role in
      the control of sleep and wakefulness.
AB  - Neurons that utilize melanin-concentrating hormone (MCH) and others that employ
      hypocretin as neurotransmitter are located in the hypothalamus and project
      diffusely throughout the CNS, including areas that participate in the generation
      and maintenance of the states of sleep and wakefulness. In the present report,
      immunohistochemical methods were employed to examine the distribution of MCHergic
      and hypocretinergic neurons. In order to test the hypothesis that the MCHergic
      system is capable of influencing specific behavioral states, we studied Fos
      immunoreactivity in MCH-containing neurons during (1) quiet wakefulness, (2)
      active wakefulness with motor activity, (3) active wakefulness without motor
      activity, (4) quiet sleep and (5) active sleep induced by carbachol (AS
      carbachol). We determined that MCHergic neuronal somata in the cat are
      intermingled with hypocretinergic neurons in the dorsal and lateral hypothalamus,
      principally in the tuberal and tuberomammillary regions; however, hypocretinergic
      neurons extended more in the anterior-posterior axis than MCHergic neurons.
      Axosomatic and axodendritic contacts were common between these neurons. In
      contrast to hypocretinergic neurons, which are known to be active during motor
      activity and AS-carbachol, Fos immunoreactivity was not observed in MCH
      containing neurons in conjunction with any of the preceding behavioral
      conditions. Non-MCHergic, non-hypocretinergic neurons that expressed c-fos during
      active wakefulness with motor activity were intermingled with MCH and hypocretin
      containing neurons, suggesting that these neurons are related to some aspect of
      motor function. Further studies are required to elucidate the functional sequela
      of the interactions between MCHergic and hypocretinergic neurons and the
      phenotype of the other neurons that were active during motor activity.

PMID- 17027937
TI  - Effect of orofacial motor cortex stimulation on neuronal activity in the red
      nucleus.
AB  - We studied modulation of the activities of the red nucleus (RN) neurons under to
      electrical stimulation of the orofacial motor cortex (OfM) in urethane
      anesthetized rats. Of 57 neurons studied, 30 (53%) neurons modulated the firing
      patterns. The firing patterns of the RN neurons were classified into four types:
      an excitation (E) type (n=4), a long inhibition (LI) type (n=4), a short
      inhibition (SI) type (n=22), and a no-effect type (n=27). These modulated neurons
      were intermingled in the dorso-ventral part of the RN. Our results suggest that
      the RN neurons receive excitatory or inhibitory inputs from the OfM.

PMID- 17027936
TI  - Subchronic administration of L-DOPA to adult rats with a unilateral 6
      hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced
      GABA release in the substantia nigra, pars reticulata.
AB  - L-DOPA is the most effective pharmacological agent used for the symptomatic
      treatment of Parkinson's disease but long-term L-DOPA treatment induces
      involuntary abnormal movements such as dyskinesias. The present study, using in
      vivo microdialysis, investigated the effects of a single or subchronic
      administration of L-DOPA to adult rats with a unilateral 6-OHDA lesion of
      dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr).
      The results indicate that a challenge injection of L-DOPA (50 mg/kg, i.p.)
      significantly increases GABA levels in the SNr of rats treated with a daily
      repeated administration of L-DOPA (50 mg/kg, i.p.). Further statistical analysis
      between groups also showed that extracellular GABA levels were significantly
      higher in the subchronic L-DOPA group than in the group receiving only one
      injection of L-DOPA. These results show that the subchronic administration of L
      DOPA results in a sensitization of enhanced extracellular GABA levels in the SNr.

PMID- 17027938
TI  - Fracture strength of direct versus indirect laminates with and without fiber
      application at the cementation interface.
AB  - OBJECTIVES: This study compared the fracture strength of direct and indirect
      resin composite laminate veneers and evaluated the effect of a bidirectional E
      glass woven fiber application at different locations at the cementation
      interface. METHODS: Standard preparations on canines (N=50, 10 per group) were
      made using a depth cutting bur (0.7mm depth) designed for laminate veneer
      restorations. Forty indirect laminates using a highly filled polymeric material
      (Estenia) and 10 direct laminates (Quadrant Anterior Shine) were prepared
      according to the manufacturer's instructions. Bidirectional E-glass woven-fiber
      sheet (0.06mm) (Everstick) was applied at different locations at the cementation
      interface. The control group received no fibers. The specimens were stored in
      water at 37 degrees C for 1 month prior to fracture testing performed in a
      universal testing machine where the load was applied from the incisal direction
      at 137 degrees (1mm/min). RESULTS: No significant differences were found between
      the five groups (P>0.01) (one-way ANOVA). While indirect laminate veneers showed
      mean fracture strength of 247+/-47N, direct laminate veneers revealed 239+/-104N.
      The use of E-glass fibers at the cementation interface at different locations did
      not increase the fracture strength significantly (286-313N) (P>0.01). Failure
      analysis showed mainly cohesive fracture of the veneer restoration (20/50) and
      adhesive failure between the cementation interface and the laminate with fiber
      exposure (19/50) covering more than half of the restorations. SIGNIFICANCE:
      Direct and indirect resin composite laminate veneers showed comparable mean
      fracture strengths. The use of E-glass woven-fiber sheet at the cementation
      interface did not increase the fracture strength of the polymeric laminate
      veneers.

PMID- 17027939
TI  - Shrinkage stress in light-cured composite resins: influence of material and
      photoactivation mode.
AB  - OBJECTIVES: The aim of this study was to record the effect of composite type and
      photoactivation mode on the stresses resulting from polymerization of five
      established composite resins: packable (Solitaire, Solitaire 2), micro-hybrid
      (Aelitefil, Z100) and hybrid (Clearfil AP-X). METHODS: A mechanical testing
      machine was used to record the polymerization contraction stress (MPa) of
      cylindrical composite specimens (d=5mm; h=2mm; C-factor=1.25) at 0.1s intervals
      over a period of 400s. The samples were photopolymerized using a halogen light
      curing device under two types of light exposure: group 1, Standard (800mW.cm(
      2)x60s); group 2, Exponential (logarithmic increase from 150 to 800mW.cm(-2) over
      15s+800mW.cm(-2)x45s). The stress rate (SR: slope(MPa>0-60s)) and the maximum
      shrinkage stress (MSS: MPa(400s)) of each material (five replications) were
      statistically analysed by one-way ANOVA/Scheffe's test and Pearson's correlation
      procedure (alpha=0.05). Finally, Student's t-test (two matched series) enabled
      the assessment of the effect of the irradiation method on the results. RESULTS:
      For group 1, in decreasing order, the MSS was 1.51+/-0.07MPa (Solitaire)
      statistically equivalent to 1.45+/-0.06MPa (Aelitefil), 1.29+/-0.08MPa (Solitaire
      2), and 1.04+/-0.03MPa (Z100) statistically equivalent to 0.92+/-0.05MPa
      (Clearfil AP-X). Z100 showed the highest SR (0.045+/-6x10(-3)) and Solitaire, the
      lowest (0.017+/-2x10(-3)). There was no correlation between SR and MSS (r<-0.33,
      p<0.05). For group 2, the MSS and SR values were distributed in a similar way to
      those from group 1. There was a negative correlation between SR and MSS (r<-0.43
      and p<0.01). The exponential ramp successfully reduced the MSS (-3.9%) and SR (
      11%) values. SIGNIFICANCE: There is no relationship between composite resin type,
      stress rate and shrinkage stress levels. The slower stress rate development,
      resulting from ramped light intensity, helped slightly to reduce the maximum
      polymerization stress.

PMID- 17027940
TI  - Synthesis of novel 2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-beta-d
      glucopyranosyl)thiazolidine-4-ones from thiosemicarbazide precursors.
AB  - To develop novel biologically active organic compounds possessing a sugar moiety,
      a series of 2-phenylsulfonylhydrazono-3-(2',3',4',6'-tetra-O-acetyl-beta-d
      glucopyranosyl)thiazolidine-4-one were synthesized via reaction of the
      thiosemicarbazide with ethyl bromoacetate. Their chemical structures were
      characterized by (1)H and (13)C NMR spectroscopy, elemental analysis and MS. The
      bioassay results indicated that some of these compound exhibit moderate
      fungicidal and herbicidal activities. Furthermore, the effect of various solvents
      at reflux temperature on the reactions of ethyl bromoacetate with the related
      thiosemicarbazides was investigated.

PMID- 17027941
TI  - Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin
      ligands.
AB  - Completely protected sialyl LewisX azide was synthesized from a neolactosamine
      azide precursor carrying a 3-O-allyloxycarbonyl group as the temporary protecting
      group. After its Pd(0)-catalyzed deprotection and stereoselective alpha
      fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the
      galactose unit and subsequent regio- and stereoselective sialylation. Reduction
      of the anomeric azido group afforded the sialyl LewisX amine building block. Two
      molecules of this tetrasaccharide ligand were conjugated to a preformed
      cyclooctapeptide containing two equidistant l-asparagine units equipped with
      carboxy-terminated tetraethyleneglycol side chains to give, after deprotection,
      the target glycopeptide conjugate. Preliminary biological evaluation of the
      synthesized bivalent sialyl LewisX cyclopeptide conjugate showed only slightly
      enhanced inhibition of E-selectin binding in spite of the given flexibility of
      the two linked saccharide determinants.

PMID- 17027942
TI  - Synthesis, characterization and thermal sensitivity of chitosan-based graft
      copolymers.
AB  - Novel chitosan-based graft copolymers (CECTS-g-PDMA) were synthesized through
      homogeneous graft copolymerization of (N,N-dimethylamino)ethyl methacrylate (DMA)
      onto N-carboxyethylchitosan (CECTS) in aqueous solution by using ammonium
      persulfate (APS) as the initiator. The effect of polymerization variables,
      including initiator concentration, monomer concentration, reaction time and
      temperature, on grafting percentage was studied. XRD, FTIR, DSC and TGA were used
      to characterize the graft copolymers. Surface-tension measurements, turbidity
      measurements and temperature-variable (1)H NMR analysis were combined to
      investigate the thermal sensitivity of CECTS-g-PDMAs in aqueous solution.

PMID- 17027943
TI  - Evaluation of thioglycosides of Kdo as glycosyl donors.
AB  - The use of Kdo thioglycosides as glycosyl donors using DMTST, IBr/AgOTf and
      NIS/AgOTf as promoters has been evaluated. Activation at low temperature allowed
      to escape the formation of 2,3-glycal byproducts to give glycosides in high yield
      and with good beta-anomeric selectivity. The use of diethyl ether as solvent and
      (especially) isopropylidene acetals as protecting groups improved the alpha
      anomeric selectivity. NIS/AgOTf as promoter surprisingly yielded the 3-iodo
      product via the glycal intermediate.

PMID- 17027944
TI  - Mechanisms of the in vivo inhibition of calcification of bioprosthetic porcine
      aortic valve cusps and aortic wall with triglycidylamine/mercapto bisphosphonate.
AB  - Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked
      heterograft materials, porcine aortic valves or bovine pericardium, have been
      widely used in cardiac surgery to treat heart valve disease. However, these
      bioprosthetic heart valves often fail in long-term clinical implants due to
      pathologic calcification of the bioprosthetic leaflets, and for stentless porcine
      aortic valve bioprostheses, bioprosthetic aortic wall calcification also
      typically occurs. Previous use of the epoxide-based crosslinker, triglycidyl
      amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior
      biocompatibility, mechanics, and calcification resistance for porcine aortic
      valve cusps (but not porcine aortic wall) and bovine pericardium, vs. Glut
      prepared controls. However, TGA preparation did not completely prevent long-term
      calcification of cusps or pericardium. Herein we report further mechanistic
      investigations of an added therapeutic component to this system, 2
      mercaptoethylidene-1,1-bisphosphonic acid (MABP), a custom synthesized thiol
      bisphosphonate, which has previously been shown in a preliminary report to
      prevent bioprosthetic heterograft biomaterial calcification when used in
      combination with initial TGA crosslinking for 7 days. In the present studies, we
      have further investigated the effectiveness of MABP in experiments that examined:
      (1) The use of MABP after optimal TGA crosslinking, in order to avoid any
      competitive interference of MABP-reactions with TGA during crosslinking; (2)
      Furthermore, recognizing the importance of alkaline phosphatase (ALP) in the
      formation of dystrophic calcific nodules, we have investigated the hypothesis
      that the mechanism by which MABP primarily functions is through the reduction of
      ALP activity. Results from cell-free model systems, cell culture studies, and rat
      subcutaneous implants, show that materials functionalized with MABP after TGA
      crosslinking have reduced ALP activity, and in vivo have no significant
      calcification in long-term implant studies. It is concluded that bioprosthetic
      heart valves prepared in this fashion are compelling alternatives for Glut
      prepared bioprostheses.

PMID- 17027945
TI  - A Nd:YAG laser-microperforated poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-basal
      membrane matrix composite film as substrate for keratinocytes.
AB  - Epithelia cultured for the treatment of ulcers, burns and for gene therapy
      applications require a flexible biomaterial for growth and transplantation that
      is adaptable to body contours. We tested several materials and found that a
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) polyester provided support
      for keratinocytes, although adhesion to this material proved to be suboptimal.
      Since epithelia adhere to the mesoderm through basal membranes, we engineered a
      basal membrane surrogate by preparing composites of PHBHV with basal membrane
      matrix (BMM). To allow cell migration into injuried areas the polyester film was
      micromachined to insert high-density micropores through a Nd:YAG laser ablation
      process. These flexible composites provided firm attachment for keratinocytes
      from the outer root sheath of human hair allowing keratinocyte migration through
      micropores. Films of microperforated PHBHV-BMM may be of use for the replacement
      of diseased or injured skin epithelia.

PMID- 17027946
TI  - Effects of oral dosing paradigms (gavage versus diet) on pharmacokinetics and
      pharmacodynamics.
AB  - In cancer chemopreventive studies, test agents are typically administered via
      diet, while the preclinical safety studies normally employ oral gavage dosing.
      Correspondence in pharmacokinetic and pharmacodynamic profiles between the two
      dosing approaches cannot be assumed a priori. Sulindac, a non-steroidal anti
      inflammatory agent with potential chemopreventive activity, was used to assess
      effects of the two oral dosing paradigms on its pharmacokinetics and
      pharmacodynamics. Time-dependent concentrations of sulindac and its sulfone
      metabolite were determined in plasma and potential target organ, mammary gland.
      Prostaglandin E(2) was used as a pharmacodynamic biomarker and measured in
      mammary gland. An inverse linear relationship was detected between
      pharmacodynamic and pharmacokinetic markers, area under the curve for
      prostaglandin E(2) levels and sulindac sulfone concentrations, respectively, in
      the mammary tissue. Marked differences in pharmacokinetics and pharmacodynamics
      were observed after administration of sulindac by the two oral dosing paradigms.
      In general, oral gavage resulted in higher peak and lower trough concentrations
      of sulindac in plasma and mammary tissue, higher area under concentration-time
      curve in plasma and mammary tissue, and greater effect on prostaglandin E(2)
      levels than the corresponding diet dosing. This study illustrates potential
      pitfalls and limitations in trying to generalize based on data obtained with
      different oral dosing schemes and their extrapolation to potential efficacy and
      health risks in humans.

PMID- 17027947
TI  - Functional characterization of human and cynomolgus monkey UDP
      glucuronosyltransferase 1A6 enzymes.
AB  - UDP-glucuronosyltransferase 1A6 (UGT1A6) is a major isoform in the human liver
      that glucuronidates numerous drugs, environmental chemicals and endogenous
      substrates. In this study, human and cynomolgus monkey UGT1A6 cDNAs (humUGT1A6
      and monUGT1A6, respectively) were cloned, and the corresponding proteins were
      heterologously expressed in yeast cells to identify the functions of primate
      UGT1A6s. The enzymatic properties of UGT1A6 proteins were characterized by the
      kinetic analysis of serotonin (5-hydroxytryptamine, 5-HT) and 4
      methylumbelliferone (4-MU) glucuronidation. humUGT1A6 and monUGT1A6 showed 96%
      identity in their nucleotide and amino acid sequences. Immunoblotting analysis
      using an antibody raised against human UGT1A6 showed that protein staining
      intensities were different between human and cynomolgus monkey UGT1A6 enzymes in
      microsomal fractions from livers and yeast cells, although both enzymes were
      detectable. The apparent K(m) value (15 mM) for 5-HT glucuronidation of
      cynomolgus monkey liver microsomes was significantly higher than that (8.6mM) of
      human liver microsomes, whereas V(max) values were lower in cynomolgus monkeys
      (2.8 nmol/min/mg protein) than in humans (8.6 nmol/min/mg protein). No
      significant species difference was observed in K(m) (approximately 90 microM) or
      V(max) (approximately 25 nmol/min/mg protein) values for liver microsomal 4-MU
      glucuronidation. In yeast cell microsomes, K(m) values (approximately 6mM) for 5
      HT glucuronidation by recombinant UGT1A6s were similar, while a V(max) value
      (0.1nmol/min/mg protein) of monUGT1A6 was significantly lower than that (0.7
      nmol/min/mg protein) of humUGT1A6. In 4-MU glucuronidation, both K(m) (210
      microM) and V(max) (3.5 nmol/min/mg protein) values of monUGT1A6 were
      significantly higher than those of humUGT1A6 (K(m), 110 microM; V(max),
      1.5nmol/min/mg protein). These findings suggest that the enzymatic properties of
      UGT1A6 were extensively different between humans and cynomolgus monkeys, although
      humUGT1A6 and monUGT1A6 showed high homology at the amino acid level. The
      information gained in this study should help with in vivo extrapolation and to
      assess the toxicity of xenobiotics.

PMID- 17027948
TI  - Phase behaviour of stearic acid-stearonitrile mixtures. A thermodynamic study in
      bulk and at the air-water interface.
AB  - The solid-liquid phase behaviour of stearic acid (SA) and stearonitrile (SN) in
      binary mixtures was investigated by differential scanning calorimetry (DSC), and
      the formation of SA-SN mixed monolayers at the air-water interface was followed
      by surface pressure-area (pi-A) measurements and by Brewster angle microscope
      (BAM) observation. The solid-liquid phase diagram is a eutectic type phase
      diagram, with the eutectic composition 0.90<X(SN)<0.95 and T(eut)=40.9 degrees C.
      The DSC results also suggest that the two components are immiscible in the solid
      phase but form a liquid mixture with positive deviations to the ideal behaviour.
      At the air-water interface, the two components form liquid condensed monolayers
      in the entire range of compositions, at low surface pressures, while solid mixed
      monolayers only form at high surface pressures for X(SN)<0.8. Thermodynamic
      analysis indicates that SA and SN are miscible in the liquid condensed phase,
      with negative deviations from the ideal behaviour. The variation of the collapse
      surface pressure of mixed monolayers also indicates miscibility at the air-water
      interface.

PMID- 17027949
TI  - A Langmuir film approach to elucidating interactions in lipid membranes: 1,2
      dipalmitoyl-sn-glycero-3-phosphoethanolamine/cholesterol/metal cation systems.
AB  - The interactions between two membrane lipids, 1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine (DPPE) and cholesterol (CHOL), were studied in Langmuir films
      using surface pressure isotherms and Brewster angle microscopy. The DPPE/CHOL
      interactions were probed for chosen monolayer and subphase (Na(+), Ca(2+))
      composition at 20, 25, and 30 degrees C. The results obtained show that DPPE and
      CHOL are miscible for the cholesterol mol fractions x(CHOL)=0.3-0.5. Cholesterol
      induces condensation of the DPPE monolayers. The most significant condensation of
      the DPPE/CHOL monolayers was observed in the presence of Ca(2+) ions in the
      subphase at x(CHOL)=0.4. The negative deviation of the molecular surface area
      (MMA) additivity from the ideal behavior together with negative values of excess
      free enthalpy of mixing in the monolayers were interpreted in terms of attractive
      interactions between lipid molecules.

PMID- 17027950
TI  - Interaction of lead with some essential trace metals in the blood of anemic
      children from Lucknow, India.
AB  - BACKGROUND: The effects of lead on the hematological system results in the
      inhibition of heme synthesis and in anemia. Lead may affect the absorption and
      metabolism of essential trace metals also. There is little information especially
      from the northern region of India regarding the relationship between blood lead
      levels>or=10 microg/dl and anemia in children. We performed a cross-sectional
      study to evaluate the association of blood lead levels>or=10 microg/dl with
      anemia, and its effect on hematological system and some essential trace metals in
      children. METHODS: A total of 75 children aged 1-7 years, 50 anemic (Hb<or=8 g%)
      and 25 non-anemic (Hb>8 g%), drawn from Lucknow, India and nearby areas were
      recruited to determine blood levels of lead, iron, zinc, copper, and calcium
      along with hematological parameters [delta-aminolevulinic acid dehydratase (delta
      ALAD) hemoglobin (Hb), hematocrit, and ascorbic acid]. RESULTS: Based on Centre
      for Disease Control and Prevention's intervention level of blood lead, children
      were categorized into those with blood lead<10 microg/dl (6.89+/-2.44) (n=19)
      (GI) and those with blood lead<10 microg/dl (21.86+/-7.58) (n=56) (GII). After
      adjustment for child's age, sex, and area of residence, children with blood lead
      levels>or=10 microg/dl were 2.87 (95% CI: 1.60-2.87) times as likely to have
      anemia as children with blood lead levels<10 microg/dl. The differences of the
      adjusted mean values of Hb, delta-ALAD, and hematocrit were significantly lower
      in children from the GII group when compared to children from the GI group
      (p<0.01, p<0.01, and p<0.05, respectively). Among essential trace metals,
      adjusted mean levels of blood iron, zinc, and calcium were significantly lower in
      GII as compared to GI (P<0.05 each). There were significant negative correlations
      of blood lead levels with delta-ALAD (r=-0.612, p<0.01), hematocrit (r=-0.427,
      p<0.05), iron (r=-0.552, p<0.05) zinc (r=-0.427, p<0.05), and calcium (r=-0.324,
      p<0.05). CONCLUSION: Results indicate that elevated blood lead levels (>or=10
      microg/dl) in children were significantly associated with risk of anemia and that
      blood lead levels also influenced the status of essential trace metals. However,
      results of this study may be limited due to limited sample size but certainly
      form the basis of a larger sample size study, taking into account all the known
      potential confounders of anemia in children.

PMID- 17027951
TI  - Comparison of plasma beta-globin DNA and S-100 protein concentrations in acute
      stroke.
AB  - BACKGROUND: This study aimed to compare changes in plasma beta-globin DNA and
      serum S100 protein to diagnose stroke and for predicting mortality and morbidity.
      METHODS: Patients with stroke-like symptoms presenting to the emergency
      department of a Hong Kong hospital were recruited. Plasma DNA was analyzed for
      the beta-globin gene with fluorescent-based PCR. S100 concentrations were
      determined using ELISA. Primary outcomes were diagnosis of stroke, mortality, and
      modified Rankin Score (mRS) after 6 months. RESULTS: One hundred ninety-seven
      consecutive patients recruited, 118 (60%) ischemic stroke, 35 (18%) hemorrhage
      and 44 (22%) with no acute neuroimaging changes. Serum S100 and plasma DNA were
      increased in 126 (p<0.0010) and 36 (p=0.21) stroke patients respectively vs.
      controls. Median plasma DNA was higher in hemorrhagic stroke than those without
      (1725 vs. 1050 kilogenome-equivalents/l, p=0.0104). Median plasma DNA was higher
      in mRS>2 vs. mRS<or=2 (1350 vs. 1025, p=0.0103), and higher in non-survivors vs.
      survivors (1625 vs. 1050, p=0.0070). Median serum S100 higher in mRS>2 patients
      vs. mRS<or=2 (0.152 vs. 0.131 microg/l, p=0.0003). The odds ratio (OR) of
      discriminating hemorrhagic from non-hemorrhagic stroke with DNA was 4.24 (95% CI
      1.88-9.56); S100 and DNA together give an OR of 16.55. CONCLUSION: For stroke
      diagnosis, S100 performs better than DNA; DNA is a better marker for hemorrhage.
      For diagnosis of hemorrhagic stroke, combined S100 and DNA performs better than
      either alone. Plasma DNA and serum S100 predict morbidity and mortality in
      stroke.

PMID- 17027952
TI  - Multiple strand displacement amplification of DNA isolated from human archival
      plasma/serum: identification of cytokine polymorphism by pyrosequencing analysis.
AB  - BACKGROUND: DNA isolation from formalin-fixed paraffin-embedded tissue appears to
      be problematic due to degradation caused by fixative. Our aim was to investigate
      if the isolated genomic DNA from archival plasma/serum, combined with multiple
      strand displacement amplification (MDA) can be used for genotyping. METHODS: Nine
      archival plasma/serum samples and freshly frozen gastric biopsies from the same
      nine H. pylori-infected subjects were used for DNA isolation. Subsequently, MDA
      DNA derived from the plasma/serum samples and DNA isolated from the antrum
      biopsies were analyzed by PCR amplification and pyrosequencing for the presence
      of interleukin-1beta gene (IL-1B) single nucleotide polymorphism (SNP). In
      addition, Southern blot and pyrosequencing analysis of H. pylori-specific PCR
      amplicons were performed. RESULTS: IL-1B SNP profiles obtained from the
      plasma/serum MDA-DNA and antrum biopsy DNA were identical. A C/C genotype was
      observed in 7 of 9 samples, and 2 of 9 revealed a C/T genotype for IL-1B -511.
      Similarly, 7 of 9 had a T/T, and 2 of 9 had a C/T genotype for IL-1B -31; 4 of 9
      had a C/C, 4 of 9 had a C/T, and 1 of 9 had a T/T genotype, respectively, for IL
      1B +3954. Moreover, pyrosequencing analysis revealed the presence of H. pylori
      26695 and J99-like 16S rDNA variable V3 region sequence motifs in the antrum
      biopsies but not in the plasma/serum samples. CONCLUSIONS: We conclude that MDA
      combined with pyrosequencing enables a rapid and accurate molecular typing of
      cytokine single nucleotide polymorphisms from archival plasma/serum samples.

PMID- 17027953
TI  - Detection of molecular variants of prolactin in human serum, evaluation of a
      method based on ultrafiltration.
AB  - BACKGROUND: In human blood, there are several molecular variants of prolactin
      with different biological effects. There is a need for new methods to detect and
      quantify these variants in order to fully understand the pathophysiological role
      of prolactin. METHODS: A method based on ultrafiltration was optimized, validated
      and compared to PEG precipitation. Serum samples from 84 patients were analyzed
      before and after pre treatment on two immunoassays, Elecsys (Roche) and Access
      (Beckman). Protein G precipitation was used to confirm presence of
      macroprolactin. RESULTS: The recovery of prolactin after ultrafiltration was
      lower than after PEG precipitation. A limit of 40% recovery after PEG
      precipitation corresponded to 27% recovery after ultrafiltration. Using these
      limits there were total agreement regarding detection of macroprolactin
      (r(s)=0.96). In contrast, recovery of prolactin in samples without macroprolactin
      showed a considerable disagreement between ultrafiltration and PEG precipitation
      (r(s)=0.48). Within-run CV was 4% for the ultrafiltration method. The correlation
      coefficient (r) between the immunoassays was 0.96 after ultrafiltration.
      CONCLUSIONS: Ultrafiltration can be used to compare different prolactin
      immunoassays and to detect macroprolactin in assays with interference from PEG.
      For samples without macroprolactin ultrafiltration may give additional
      information reflecting individual variations of other molecular variants of
      prolactin.

PMID- 17027954
TI  - What is stage II in high-grade primary gastric lymphoma? How to define the range
      of "localized disease".
AB  - We conducted a retrospective analysis to evaluate the Musshoff staging system for
      high-grade primary gastric lymphoma (HG-PGL), particularly in those patients with
      stages IE and IIE localized diseases. One hundred twenty-six patients presented
      with stage IE or IIE diseases were retrospectively reclassified on the basis of a
      pretreatment CT examination as to whether there was lymph node involvement. A
      positive M1 node (by AJCC staging system) on pretreatment CT scanning was
      associated with poor clinical outcome for localized stage I or II patients.

PMID- 17027955
TI  - Quantum dot labeling and tracking of human leukemic, bone marrow and cord blood
      cells.
AB  - Quantum dots (QDs) are nanometer scale fluorescent semiconductors that are
      increasingly used as labeling tools in biological research. These nanoparticles
      have physical properties, such as high quantum yield and resistance to
      photobleaching, that make them attractive molecular probes for tracking
      hematologic cells. Here, we show that QDs attached to a transporter protein
      effectively label all hematologic cells tested, including cell lines and
      malignant and non-malignant patient samples. We demonstrate that dividing cells
      can be tracked through at least four cell divisions. In leukemic cell lines, some
      cells remain labeled for 2 weeks. We show that QDs can be used to follow cells as
      they differentiate. QDs are seen in monocyte-like and neutrophil-like progeny of
      labeled HL-60 myeloblasts exposed to Vitamin D analogues and DMSO, respectively.
      QDs are also observed in monocytes generated from labeled CD34+ cells. In
      addition, QDs attached to streptavidin can target cells with differing cell
      surface markers, including CD33. In summary, QDs have the ability to bind to
      specific cells of interest, be taken up by a diverse range of hematologic cells,
      and followed through many divisions and through differentiation. These results
      establish QDs as extremely useful molecular imaging tools for the study of
      hematologic cells.

PMID- 17027956
TI  - WUSCHEL regulates cell differentiation during anther development.
AB  - During anther development a series of cell specification events establishes the
      male gametophyte and the surrounding sporophytic structure. Here we show that the
      homeobox gene WUSCHEL, originally identified as a central regulator of stem cell
      maintenance, plays an important role in cell type specification during male
      organogenesis. WUS expression is initiated very early during anther development
      in the precursor cells of the stomium and terminates just before the stomium
      cells enter terminal differentiation. At this stage the stomium cells and the
      neighboring septum cells that separate the pollen sacs undergo typical cell wall
      thickening and degenerate which leads to rupture of the anther and pollen
      release. In wus mutants, neither stomium cells nor septum cells differentiate or
      undergo cell death and degenerate. As a consequence, the anther stays intact and
      pollen is not released. CLAVATA3 which is activated by WUS in stem cell
      maintenance, is not activated in anthers indicating a novel pathway regulated by
      WUS. Comparing WUS function in stem cell maintenance and sexual organ development
      suggests that WUS expressing cells represent a conserved signaling module that
      regulates behavior and communication of undifferentiated cells.

PMID- 17027957
TI  - Analysis of cytoskeletal and motility proteins in the sea urchin genome assembly.
AB  - The sea urchin embryo is a classical model system for studying the role of the
      cytoskeleton in such events as fertilization, mitosis, cleavage, cell migration
      and gastrulation. We have conducted an analysis of gene models derived from the
      Strongylocentrotus purpuratus genome assembly and have gathered strong evidence
      for the existence of multiple gene families encoding cytoskeletal proteins and
      their regulators in sea urchin. While many cytoskeletal genes have been cloned
      from sea urchin with sequences already existing in public databases, genome
      analysis reveals a significantly higher degree of diversity within certain gene
      families. Furthermore, genes are described corresponding to homologs of
      cytoskeletal proteins not previously documented in sea urchins. To illustrate the
      varying degree of sequence diversity that exists within cytoskeletal gene
      families, we conducted an analysis of genes encoding actins, specific actin
      binding proteins, myosins, tubulins, kinesins, dyneins, specific microtubule
      associated proteins, and intermediate filaments. We conducted ontological
      analysis of select genes to better understand the relatedness of urchin
      cytoskeletal genes to those of other deuterostomes. We analyzed developmental
      expression (EST) data to confirm the existence of select gene models and to
      understand their differential expression during various stages of early
      development.

PMID- 17027958
TI  - Hippi is essential for node cilia assembly and Sonic hedgehog signaling.
AB  - Hippi functions as an adapter protein that mediates pro-apoptotic signaling from
      poly-glutamine-expanded huntingtin, an established cause of Huntington disease,
      to the extrinsic cell death pathway. To explore other functions of Hippi we
      generated Hippi knock-out mice. This deletion causes randomization of the embryo
      turning process and heart looping, which are hallmarks of defective left-right
      (LR) axis patterning. We report that motile monocilia normally present at the
      surface of the embryonic node, and proposed to initiate the break in LR symmetry,
      are absent on Hippi-/- embryos. Furthermore, defects in central nervous system
      development are observed. The Sonic hedgehog (Shh) pathway is downregulated in
      the neural tube in the absence of Hippi, which results in failure to establish
      ventral neural cell fate. Together, these findings demonstrate a dual role for
      Hippi in cilia assembly and Shh signaling during development, in addition to its
      proposed role in apoptosis signal transduction in the adult brain under
      pathogenically stressful conditions.

PMID- 17027959
TI  - Xenopus fibrillin regulates directed convergence and extension.
AB  - Fibrillin-based human diseases such as Marfan syndrome and congenital
      contractural arachnodactyly implicate fibrillins in the function and homeostasis
      of multiple adult tissues. Fibrillins are also expressed in embryos, but no early
      developmental role has been described for these proteins. We use three
      independent methods to reveal a role for Xenopus fibrillin (XF) at gastrulation.
      First, expressing truncated forms of XF in the embryo leads to failure of
      gastrulation concomitant with a dominant-negative effect on native fibrillin
      fibril assembly. Expressing truncated XF also inhibits normal progression of the
      patterned, polarized cell motility that drives convergence and extension at
      gastrulation and perturbs directed extension in cultured explants of dorsal
      mesoderm. Second, injection of a synthetic peptide encoding a cell-binding domain
      of XF into midgastrula embryos causes acute failure of gastrulation associated
      with defective fibrillin fibril assembly. These injections also reveal a critical
      role for this peptide in the fibril assembly process. Third, morpholino-mediated
      knockdown of translation of XF in the embryo also perturbs normal gastrulation
      and directed extension. Together, these data show that native Xenopus fibrillin
      is essential for the process of directed convergent extension in presumptive
      notochord at gastrulation.

PMID- 17027960
TI  - Mobilization of the gonococcal 5.2 kb beta-lactamase plasmid pSJ5.2 into
      Escherichia coli by cointegration with several gram-conjugative plasmids.
AB  - We report the mobilization by cointegration of the gonococcal 5.2 kb beta
      lactamase plasmid pSJ5.2 in an Escherichia coli background. Transfer of pSJ5.2
      was measured by filter mating assays with five different conjugative plasmids
      from Enterobacteriaceae and the gonococcal 41 kb tet(M). Plasmid pSJ5.2 was
      mobilized to E. coli at frequencies of 1.7x10(-6), 9.3x10(-8) and 2.7x10(-5) by
      the tet(M), R64 drd-33 and N3 conjugative plasmids, respectively. Mobilization of
      pSJ5.2 by the 41 kb tet(M) conjugative plasmid resulted in stable Amp(R) E. coli
      transconjugants consisting of pSJ5.2 plasmid with an insertion located in the 2.4
      kb BamHI-BamHI fragment. Mobilization of pSJ5.2 by R64drd-33 and N3 conjugative
      plasmids involved stable cointegrates as detected by Southern Blot with a DIG
      labelled PstI-digested pSJ5.2 probe. Restriction analysis of the R64::pSJ5.2 and
      N3::pSJ5.2 cointegrates and Southern Blot with the pSJ5.2 probe showed that
      cointegrates formed by deletion of DNA regions within the 1.8 kb BamHI-HindIII
      fragment of pSJ5.2. The plasmid thus appears to use multiple recombination
      mechanisms for cointegration with different conjugative plasmids. The complete
      nucleotide sequence of pSJ5.2 was determined, and will be a useful tool to
      further investigate the molecular mechanisms leading to its cointegrative
      transfer.

PMID- 17027961
TI  - Effects of peripheral-type benzodiazepine receptor ligands on Ehrlich tumor cell
      proliferation.
AB  - Peripheral-type benzodiazepine receptors have been found throughout the body, and
      particularly, in high numbers, in neoplastic tissues such as the ovary, liver,
      colon, breast, prostate and brain cancer. Peripheral-type benzodiazepine receptor
      expression has been associated with tumor malignity, and its subcellular
      localization is important to define its function in tumor cells. We investigated
      the presence of peripheral-type benzodiazepine receptors in Ehrlich tumor cells,
      and the in vitro effects of peripheral-type benzodiazepine receptors ligands on
      tumor cell proliferation. Our results demonstrate the presence of peripheral-type
      benzodiazepine receptor in the nucleus of Ehrlich tumor cells (85.53+/-12.60%).
      They also show that diazepam and Ro5-4864 (peripheral-type benzodiazepine
      receptor agonists) but not clonazepam (a molecule with low affinity for the
      peripheral-type benzodiazepine receptor) decreased the percentage of tumor cells
      in G0-G1 phases and increased that of cells in S-G2-M phases. The effects of
      those agonists were prevented by PK11195 (a peripheral-type benzodiazepine
      receptor antagonist) that did not produce effects by itself. Altogether, these
      data suggest that the presence of peripheral-type benzodiazepine receptor within
      the nucleus of Ehrlich tumor cells is associated with tumor malignity and
      proliferation capacity.

PMID- 17027962
TI  - Spinal and pontine alpha2-adrenoceptors have opposite effects on pain-related
      behavior in the neuropathic rat.
AB  - Descending noradrenergic pathways contribute to feedback inhibition of pain by
      releasing norepinephrine in the spinal cord. Noradrenergic nuclei in the pons
      contain abundant alpha(2)-adrenoceptors. We assessed the contribution of pontine
      alpha(2)-adrenoceptors to endogenous regulation of pain in nerve-injured rats.
      Tactile allodynia and mechanical hyperalgesia were assessed in the injured
      dermatome and heat nociception in an uninjured dermatome. Atipamezole, an
      alpha(2)-adrenoceptor antagonist, or saline was administered systemically or
      microinjected into the locus coeruleus, the lateral parabrachial nucleus, the
      central nucleus of the amygdala, the midbrain periaqueductal gray, and/or through
      an intrathecal (i.t.) catheter to the spinal cord. Atipamezole administered
      systemically, into the amygdala or the periaqueductal gray had no significant
      effects on pain behavior. Atipamezole (0.3-5 microg) microinjected into the pons,
      the locus coeruleus or the lateral parabrachial nucleus, produced a selective and
      dose-related antiallodynia, which was reversed by i.t. administration of
      atipamezole (5 microg). I.t. administration of atipamezole alone (5 microg)
      produced thermal hypersensitivity in the non-neuropathic segment (tail) of nerve
      injured animals. In sham-operated controls, i.t. administration of atipamezole
      had no effect. Suppression of heat nociception in uninjured dermatomes of nerve
      injured but not the control animals following i.t. administration of atipamezole
      indicates that nerve injury produced a tonic activation of noradrenergic feedback
      inhibition acting on spinal alpha(2)-adrenoceptors. In parallel, antiallodynia
      induced by pontine administration of atipamezole indicates that nerve injury
      induces a tonic activation of pontine alpha(2)-adrenoceptors that promotes
      neuropathic hypersensitivity by attenuating descending inhibition. Thus, spinal
      and pontine alpha(2)-adrenoceptors have opposite effects on pain-related behavior
      in neuropathic animals.

PMID- 17027963
TI  - Pharmacological characteristics of endothelium-derived hyperpolarizing factor
      mediated relaxation of small mesenteric arteries from db/db mice.
AB  - Endothelial dysfunction is considered as a major risk factor of cardiovascular
      complications of type I and type II diabetes. Our previous studies have
      demonstrated that endothelial dysfunction in the small mesenteric arteries from
      12-16 week old type II diabetic mice was associated with decreased bio
      availability of nitric oxide whereas endothelium-derived hyperpolarizing factor
      (EDHF)-mediated relaxation was preserved. The objective of the present study was
      to characterize EDHF-mediated relaxations of small mesenteric arteries from db/db
      mice. A depolarizing concentration of KCl or tetraethylammonium (TEA, 10 mM)
      significantly inhibited the EDHF-mediated relaxation to acetylcholine and
      bradykinin in small mesenteric arteries from both db/+ and db/db mice.
      Charybdotoxin or iberiotoxin alone and a combination of ouabain and barium
      significantly reduced the maximal relaxation to acetylcholine in small mesenteric
      arteries from db/db mice and charybdotoxin or iberiotoxin either alone or in
      combination with apamin reduced the sensitivity to the EDHF-mediated component of
      the relaxation response to bradykinin. 17-octadecynoic acid, but not catalase,
      significantly reduced the sensitivity to EDHF-mediated responses to bradykinin in
      db/db mice; 17-octadecynoic acid had no effect on acetylcholine-mediated
      relaxations. No differences were, however, detected for mRNA expression levels of
      calcium-activated potassium channels or connexins 37, 40, 43 and 45.
      Collectively, these data suggest that bradykinin-induced, EDHF-dependent
      relaxation in small mesenteric arteries from db/db mice is mediated via
      cytochrome P450 product that activates the large conductance calcium-activated
      potassium (BK(Ca) or Slo) channel, whereas the acetylcholine-induced, EDHF
      mediated relaxation involves neither cytochrome P450 product nor hydrogen
      peroxide.

PMID- 17027964
TI  - Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium
      independent relaxation via the cyclic AMP pathway in porcine coronary artery.
AB  - Puerarin, an isoflavonoid derived from the Chinese medicinal herb Radix
      puerariae, has been suggested to be useful in the management of various
      cardiovascular disorders. The present study examined the effect of acute exposure
      (30 min) to puerarin on vascular relaxation. Rings from porcine coronary artery
      of either sex were used. The highest concentration of puerarin (100 microM)
      produced a small but statistically significant relaxation of U46619-contracted
      rings. Vascular relaxations were also studied in the presence of lower
      concentrations of puerarin (0.1, 1 and 10 microM) which had no direct relaxation
      effect. Puerarin enhanced vasorelaxation to endothelium-independent relaxing
      agents, sodium nitroprusside and cromakalim. However, puerarin had no effect on
      vasorelaxation induced by endothelium-dependent relaxing agents, bradykinin and
      calcium ionophore A23187. The potentiating action of puerarin (10 microM) on
      sodium nitroprusside-mediated relaxation was not affected by the nitric oxide
      synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM),
      or by the disruption of the endothelium with Triton X-100. The effect of puerarin
      was reversible following a washout period. The potentiating effects were
      comparable with the 3'-5'-cyclic adenosine monophosphate (cyclic AMP) analogues,
      8-bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP; 10 muM) and Sp
      isomer [S nomenclature refers to phosphorus] of adenosine-3', 5'-cyclic
      monophosphorothioate (Sp-cyclic AMPS; 3 microM), but not the 3'-5'-cyclic
      guanosine monophosphate (cyclic GMP) analogue, 8-bromoguanosine-3'-5'-cyclic
      monophosphate (8-Br-cyclic GMP; 3 microM). The cyclic AMP antagonist, Rp-isomer
      [R nomenclature refers to phosphorus] of 8-bromoadenosine-3', 5'-cyclic
      monophosphorothioate (Rp-8-Br-cyclic AMPS; 10 microM), but not cyclic GMP
      antagonist, Rp-isomer of 8-bromoguanosine-3', 5'-cyclic monophosphorothioate (Rp
      8-Br-cyclic GMPS; 10 microM), reversed the effects of puerarin (10 microM) on the
      enhancement of vasorelaxation to sodium nitroprusside. Our results demonstrated
      that puerarin enhanced sodium nitroprusside-induced relaxation, possibly via the
      cyclic AMP-dependent pathway.

PMID- 17027965
TI  - Differential effects of cyclooxygenase inhibitors on intracerebroventricular
      colchicine-induced dysfunction and oxidative stress in rats.
AB  - Alzheimer's disease is a progressive neurological and psychiatric disorder.
      Oxidative stress and neuroinflammation have been implicated in pathophysiology of
      Alzheimer's disease. Inflammatory cells, such as astrocytes and microglia, are
      activated in areas of the brain affected by amyloid plaques and inflammatory
      mediators including cytokines, chemokines, prostaglandins, oxygen free radicals
      and reactive nitrogen species may have a crucial role in Alzheimer's disease
      pathogenesis. Central administration of colchicine, a microtubule-disrupting
      agent, causes loss of cholinergic neurons and cognitive dysfunction that is
      associated with excessive free radical generation. The present study was aimed to
      evaluate the effects of cyclooxygenase inhibitors against colchicine-induced
      cognitive dysfunction and oxidative stress in rats. Following
      intracerebroventricular (i.c.v.) administration of colchicine (15 microg/5
      microl), rats exhibited poor retention of memory in Morris water maze and
      elevated plus maze task paradigms and oxidative stress in rats. Chronic treatment
      with naproxen (per se; 20 and 40 mg/kg, p.o.) or valdecoxib (per se; 5 and 10
      mg/kg, p.o.) daily respectively for a period of 25 days beginning 4 days prior to
      colchicine injection significantly improved colchicine-induced cognitive
      impairment. Intracerebroventricular colchicine injection resulted in free radical
      generation characterized by alterations in oxidative stress markers with a
      significant increase in malondialdehyde and nitrite levels and depletion of
      reduced glutathione levels in the brains of rats. It also caused a decrease in
      acetylcholinesterase activity. Besides, improving cognitive dysfunction, chronic
      administration of cyclooxygenase inhibitors (naproxen and valdecoxib)
      significantly reduced elevated malondialdehyde, nitrite levels and restored
      reduced glutathione levels and acetylcholinesterase activity. The results of the
      present study indicated that naproxen (per se; 20 and 40 mg/kg, p.o.) or
      valdecoxib (per se; 5 and 10 mg/kg, p.o.) treatment has a neuroprotective role
      against colchicine-induced cognitive impairment and associated oxidative stress.
      The present findings further support the potential use of cyclooxygenase
      inhibitors in treatment of neurodegenerative diseases such as Alzheimer's
      disease.

PMID- 17027966
TI  - Determining when contamination is pollution - weight of evidence determinations
      for sediments and effluents.
AB  - Contamination is simply the presence of a substance where it should not be or at
      concentrations above background. Pollution is contamination that results in or
      can result in adverse biological effects to resident communities. All pollutants
      are contaminants, but not all contaminants are pollutants. Differentiating
      pollution from contamination cannot be done solely on the basis of chemical
      analyses because such analyses provide no information on bioavailability or on
      toxicity. Effects-based measures such as laboratory or field toxicity tests and
      measures of the status of resident, exposed communities provide key information,
      but cannot be used independently to determine pollution status. Laboratory
      studies can be predictive, but are rarely realistic. Measures of resident
      communities include innate natural variability and cannot easily distinguish
      between adaptation to contamination (a genetic process) and acclimation (a
      physiological process that may decrease energy reserves, possibly reducing such
      critical population-level parameters as reproduction). Finally, contaminant
      effects may not only be direct but also indirect; predicting such effects
      requires knowledge of the system under study as well as appropriate use of lines
      of evidence (LOE) such as toxicity tests directed to key species. Consequently,
      in sediments, effluents or other inputs/environmental compartments, determining
      when contamination is or may in future become pollution, requires a weight of
      evidence (WOE) assessment using different LOE appropriate to the situation under
      investigation. WOE investigations provide two different types of information:
      definitive conclusions regarding pollution; or, information as to what
      additional, investigative studies are necessary for definitive conclusions.
      Effectively, a WOE assessment comprises an initial screening-level ecological
      risk assessment (ERA), which may be followed by a detailed-level ERA if key
      uncertainties need to be resolved.

PMID- 17027967
TI  - Dock4 is regulated by RhoG and promotes Rac-dependent cell migration.
AB  - Cell migration is essential for normal development and many pathological
      processes including tumor metastasis. Rho family GTPases play important roles in
      this event. In particular, Rac is required for lamellipodia formation at the
      leading edge during migration. Dock4 is a member of the Dock180 family proteins,
      and Dock4 mutations are present in a subset of human cancer cell lines. However,
      the function and the regulatory mechanism of Dock4 remain unclear. Here we show
      that Dock4 is regulated by the small GTPase RhoG and its effector ELMO and
      promotes cell migration by activating Rac1. Dock4 formed a complex with ELMO, and
      expression of active RhoG induced translocation of the Dock4-ELMO complex from
      the cytoplasm to the plasma membrane and enhanced the Dock4- and ELMO-dependent
      Rac1 activation and cell migration. On the other hand, RNA interference-mediated
      knockdown of Dock4 in NIH3T3 cells reduced cell migration. Taken together, these
      results suggest that Dock4 plays an important role in the regulation of cell
      migration through activation of Rac1, and that RhoG is a key upstream regulator
      for Dock4.

PMID- 17027968
TI  - P-gp localization in mitochondria and its functional characterization in multiple
      drug-resistant cell lines.
AB  - Multidrug resistance (MDR) phenotype is characterized by the over-expression of P
      glycoprotein (P-gp) on cell plasma membranes that extrudes several drugs out of
      cells. Cells that express the MDR phenotype are resistant to the mitochondrial
      related apoptosis and to several anticancer drugs. This study assessed the
      presence of P-gp in mitochondria and its role in parental drug-sensitive (P5) and
      in P5-derived MDR1 cells P1(0.5) hepatocellular carcinoma (HCC) cell lines and in
      drug-sensitive (PSI-2) and mdr1-transfected (PN1A) NIH/3T3 cells. By using
      Western blot analysis, confocal laser microscopy, measurements of Rhodamine 123
      transport across mitochondrial membranes, MDR1 small interfering RNA and flow
      cytometry analysis, experiments indicate that P-gp is expressed in mitochondria
      of P1(0.5) and PN1A cells and it is functionally active. Rho 123 accumulation was
      largely reduced in mitochondria of P1(0.5) cells as compared to those of P5
      cells; the reduced uptake of fluorescence in mitochondria of MDR cells was due to
      P-gp-mediated Rho 123 efflux. In conclusion, these data demonstrate that
      functionally active P-gp is expressed in the mitochondrial membrane of MDR
      positive cells and pumps out anticancer drugs from mitochondria into cytosol.
      Therefore, P-gp could be involved in the protection of mitochondrial DNA from
      damage due to antiproliferative drugs.

PMID- 17027969
TI  - Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of
      the receptor tyrosine kinase DDR1.
AB  - Cell migration plays a central role in processes such as development, wound
      healing and cancer metastasis. Here we describe a novel interaction between DDR1,
      a receptor tyrosine kinase activated by collagen, and the phosphoprotein DARPP-32
      in mammary epithelial cells. DARPP-32 expression was readily detected in non
      transformed mammary cell lines, but was strongly reduced or even absent in breast
      tumor cell lines, such as MCF7. Transfection of MCF7 cells with DARPP-32 resulted
      in severely impaired cell migration, while DARPP-32 transfection into the DDR1
      deficient breast cancer cell line MDA-MB-231 did not alter migration. Co
      expression of both DDR1 and DARPP-32 in MDA-MB-231 cells inhibited migration,
      thereby supporting a critical role of the DDR1/DARPP-32 complex in motility.
      Mutational substitution of the phosphorylation sites Thr-34 or Thr-75 on DARPP-32
      revealed that phosphorylation of Thr-34 is necessary for the ability of DARPP-32
      to impair breast tumor cell migration. Thus, DARPP-32 signaling downstream of
      DDR1 is a potential new target for effective anti-metastatic breast cancer
      therapy.

PMID- 17027970
TI  - Involvement of caspase-3, lipid peroxidation and TNF-alpha in causing apoptosis
      of macrophages by coordinately expressed Salmonella phenotype under stress
      conditions.
AB  - Invasive Salmonella has been reported to induce apoptosis of macrophages as a
      part of its infection process, which may allow it to avoid detection by the
      innate immune system. However, the bacterial components capable of inducing
      apoptosis, particularly under the environments offered by the host have not been
      fully identified. Therefore, in the present study, attempts were made to evaluate
      the apoptotic potential of Salmonella enterica serovar Typhi (S. typhi) outer
      membrane protein expressed under stress conditions like iron, oxidative and
      anaerobic simulating the in vivo situations encountered by the pathogen. Analysis
      of data revealed that a coordinately expressed 69kDa outer membrane protein (OMP)
      expressed with enhanced intensity under iron, oxidative and anaerobic stress
      conditions caused apoptotic cell death in 51% of macrophages, whereas OMPs of S.
      typhi extracted under normal conditions accounted for apoptotic cell death in
      only 31% of macrophages. A significantly enhanced activity of caspase-3 was
      observed during macrophage-apoptosis induced by this protein. A significant
      increase in the extent of lipid peroxidation (levels of oxidant) and decrease in
      the activities of antioxidants was also observed which correlated with the
      increased generation of tumor necrosis factor-alpha, interleukine-1alpha and
      interleukine-6. These results suggest that caspase-3 and tumor necrosis factor
      alpha in conjunction with other cytokines may induce apoptotic cell death through
      the up-regulation of oxidants and down-regulation of antioxidants. These findings
      may be relevant for the better understanding of the disease pathophysiology and
      for the future developments of diagnostic and preventive strategies during the
      host-pathogen interactions.

PMID- 17027971
TI  - Factors affecting outflow facility calculations.

PMID- 17027972
TI  - Systemic bevacizumab (Avastin) therapy for neovascular age-related macular
      degeneration: twenty-four-week results of an uncontrolled open-label clinical
      study.
AB  - PURPOSE: To evaluate the safety, efficacy, and durability of bevacizumab for the
      treatment of subfoveal choroidal neovascularization (CNV) in patients with
      neovascular age-related macular degeneration (AMD). DESIGN: Open-label, single
      center, uncontrolled clinical study. PARTICIPANTS: Age-related macular
      degeneration patients with subfoveal CNV (n = 18) and best-corrected visual
      acuity (VA) letter scores of 70 to 20 (approximate Snellen equivalent, 20/40
      20/400). METHODS: Patients were treated at baseline with an intravenous infusion
      of bevacizumab (5 mg/kg) followed by 1 or 2 additional doses given at 2-week
      intervals. Safety assessments were performed at all visits. Ophthalmologic
      evaluations included protocol VA measurements, ocular examinations, and optical
      coherence tomography (OCT) imaging at each visit. Retreatment with bevacizumab
      was performed if there was evidence of recurrent CNV. MAIN OUTCOME MEASURES:
      Assessments of safety and changes from baseline in VA scores and OCT measurements
      were performed through 24 weeks. RESULTS: No serious ocular or systemic adverse
      events were identified through 24 weeks. The only adverse event identified was a
      mild elevation of mean systolic and diastolic blood pressure measurements (+11
      mmHg, P = 0.004; +8 mmHg, P<0.001) evident by 3 weeks and easily controlled with
      antihypertensive medications. By 24 weeks, the systolic and diastolic mean blood
      pressures were at or below baseline measurements. Visual acuity in the study eyes
      improved within the first 2 weeks, and by 24 weeks, the mean VA letter score
      increased by 14 letters in the study eyes (P<0.001), and the mean OCT central
      retinal thickness measurement decreased by 112 microm (P<0.001). By 24 weeks,
      retreatment was needed for only 6 of the 18 study eyes, and after retreatment,
      the recurrent leakage was eliminated, with restoration of any lost VA.
      CONCLUSIONS: Systemic bevacizumab therapy for neovascular AMD was well tolerated
      and effective for all 18 patients through 24 weeks. By 6 months, most patients
      did not require any additional treatment beyond the initial 2 or 3 infusions.
      Despite these impressive results, it is unlikely that systemic bevacizumab will
      be studied in a large clinical trial because of the potential risks associated
      with systemic anti-VEGF therapy and the perception that intravitreal therapy is
      safer.

PMID- 17027973
TI  - Leishmania donovani: dyskinetoplastid cells survive and proliferate in the
      presence of pyruvate and uridine but do not undergo apoptosis after treatment
      with camptothecin.
AB  - We have shown that treatment with luteolin in leishmanial cells causes loss of mt
      DNA and induces apoptosis through mitochondria dependent pathway [Sen, N., Das,
      B.B., Ganguly, A., Banerjee, B., Sen, T., Majumder, H.K., 2006. Leishmania
      donovani: intracellular ATP level regulates apoptosis-like death in luteolin
      induced dyskinetoplastid cells. Experimental Parasitology, in press]. Here, we
      report that mitochondrial DNA depleted leishmanial cells require exogenous
      sources of pyruvate and uridine to survive and proliferate. The presence of
      pyruvate and uridine in a growing media help them to produce sufficient amount of
      glycolytic ATP to maintain the mitochondrial membrane potential in the absence of
      their functional ETC. Treatment of wild type cells with CPT causes generation of
      ROS that leads to apoptosis. But unlike the normal cells ROS was not generated in
      these mt-DNA depleted cells after treatment with CPT. Taken together we have
      shown for the first time that dyskinetoplastid cells are auxotrophic for pyruvate
      and uridine and apoptosis cannot be induced in these cells in the presence of
      CPT. Therefore, the presence of mitochondrial DNA is absolutely necessary for the
      cytotoxicity of CPT in kinetoplastid parasites.

PMID- 17027974
TI  - DNA conformational changes and cleavage by ruthenium(II) nitrofurylsemicarbazone
      complexes.
AB  - Metal complexes that establish interactions with DNA are being studied not only
      because of their potential use as therapeutic agents but also as tools for
      biochemistry and molecular biology. Searching for drugs with anti-trypanosome
      activity, we previously synthesized a series of ruthenium mixed ligand dimethyl
      sulfoxide complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L is 5
      nitrofurylsemicarbazone derivatives and DMSO is dimethyl sulfoxide. Though they
      present the ability to bind DNA, no activity against parasites in cell culture
      was observed. Considering their potential application as molecular tools we
      further analyzed the interactions with DNA through an electrophoretic approach.
      Non covalent withdrawal of superhelicity and a rapid nicking activity upon
      covalent interaction was observed. Inhibition of both effects was observed in the
      presence of distamycin suggesting the involvement of the DNA minor groove in the
      interaction with the nitrofurylsemicarbazone ruthenium complexes. In addition
      cleavage inhibition by dimethyl sulfoxide suggests an oxidative mechanism of
      action.

PMID- 17027975
TI  - A role for copper in biological time-keeping.
AB  - A family of cell surface and growth related proteins that oxidize both NADH and
      hydroquinones and carry out protein disulfide-thiol interchange (ECTO-NOX
      proteins) exhibits unique characteristics. The two activities they catalyze,
      hydroquinone or NADH oxidation and protein disulfide-thiol interchange, alternate
      in CNOX (the constitutive ECTO-NOX), to generate a regular period length of
      24min. For NADH or hydroquinone oxidation each period is defined by maxima that
      recur at intervals of 24min. Here, we report that bound Cu(II) is required to
      sustain the 24min oscillation cycle of CNOX. CNOX preparations from plasma
      membranes of soybean, when unfolded in the presence of the copper chelator
      bathocuproine and refolded, lose activity. When refolded in the presence of
      copper, activity is restored. Unexpectedly, however, the released copper is
      capable of catalyzing NADH (or hydroquinone) oxidation in the absence of protein.
      Solvated Cu(II) as the chloride or other salts alone is capable of catalyzing
      NADH oxidation and the oxidation rates oscillate with an overall period length of
      24min. With Cu(II)Cl(2) the pattern consists of five maxima, two of which are
      separated by an interval of 6min and three of which are separated by intervals of
      4.5min [6min+4 (4.5min)]. The period length is independent of temperature and pH.
      The asymmetry of the oscillatory pattern is retained after solvation of the
      Cu(II) salts in D(2)O but the overall period length is increased to 30min. The
      findings suggest that the bound copper of CNOX and perhaps of ECTO-NOX proteins
      in general, is essential to maintain the structural changes that underlie the
      periodic alternations in activity that define the 24min time-keeping cycle of the
      protein.

PMID- 17027976
TI  - Mapping contacts of the S12-S7 intercistronic region of str operon mRNA with
      ribosomal protein S7 of E. coli.
AB  - In E. coli, S7 initiates 30S ribosome assembly by binding to 16S rRNA. It also
      regulates translation of the S12 and S7 cistrons of the 'streptomycin' operon
      transcript by binding to the S12-S7 intercistronic region. Here, we describe the
      contacts of N-terminally His(6)-tagged S7 with this region as mapped by UV
      induced cross-linking. The cross-links are located at U(-34), U(-35), quite
      distant from the start codons of the two cistrons. In order to explain the
      mechanism of translational repression of S12-S7, we consider a possible
      conformational rearrangement of the intercistronic RNA structure induced by S7
      binding.

PMID- 17027977
TI  - CHD6 is a DNA-dependent ATPase and localizes at nuclear sites of mRNA synthesis.
AB  - The CHD family of proteins comprises ATP-dependent chromatin remodeling enzymes,
      which combine chromodomains, with SWI2/SNF2 ATPase/helicase motifs and DNA
      binding capability. In the last few years, CHD proteins have drawn increased
      attention, because some of them were found to form large multi-subunit complexes,
      involved in transcription-related events like gene activation, suppression, or
      histone modification. We previously described the identification of CHD6, a
      protein of the CHD subfamily III. In the present study, we report that CHD6 is
      expressed in cells of human origin and in various mouse tissues. Subcellular
      distribution of CHD6 is restricted to the nucleoplasm. We further show that CHD6
      colocalizes with both hypo- and hyper-phosphorlylated forms of RNA polymerase II.
      CHD6 was found to be present at sites of mRNA synthesis and to be part of a high
      molecular weight complex. Moreover, we demonstrate DNA-dependent ATPase activity
      of CHD6.

PMID- 17027978
TI  - Depletion of Jab1 inhibits proliferation of pancreatic cancer cell lines.
AB  - Jab1 overexpression is observed in many human cancers, but its physiological
      significance remains to be investigated. We reduced the level of Jab1 expression
      in pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 by the RNA interference
      and found that Jab1-knockdown resulted in impaired cell proliferation and
      enhanced apoptosis regardless of the genotype of the tumor suppressor p53. This
      growth inhibition was rescued by the introduction of siRNA-resistant mouse Jab1
      cDNA. Jab1-knocked-down cells expressed a higher level of c-myc, and additional
      depletion of c-myc rescued cells from Jab1-knockdown-mediated growth suppression.
      Thus, Jab1 overexpression contributes to pancreatic cancer cell proliferation and
      survival. Jab1 could be a novel target in cancer therapy.

PMID- 17027979
TI  - Neurogenic effect of vascular endothelial growth factor during germ layer
      formation of human embryonic stem cells.
AB  - Vascular endothelial growth factor (VEGF), a potent mitogen for vascular
      endothelial cells, has been suggested as a modulator that is involved in
      neurogenesis as well as angiogenesis. Here, we directly examined the effect of
      VEGF on neuroectodermal differentiation using human embryonic stem cells (hESCs).
      VEGF treatment upregulated the expression of neuroectodermal genes (Sox1 and
      Nestin) during germ layer formation in embryoid bodies (EBs) and efficiently
      increased the number of neural rosettes expressing both Pax6 and Nestin. The
      neural progenitors generated from VEGF-treated EBs further differentiated into
      cells that showed a similar pattern of gene expression observed in the
      development of dopaminergic neurons upon terminal differentiation. These results
      support the neurogenic effect of VEGF on hESC differentiation.

PMID- 17027980
TI  - Caspase-mediated changes in Sir2alpha during apoptosis.
AB  - Silent information regulator 2 (Sir2) is an NAD(+)-dependent histone deacetylase
      that establishes repressive chromatin status and extends the life span of both
      budding yeast and the nematode worm Caenorhabditis elegans. There is growing
      evidence that its mammalian homologue Sir2alpha protects cells from stress
      induced apoptosis. We report here that mammalian Sir2alpha was directly cleaved
      by both initiator and executioner caspases, and relocated from the nucleus to the
      cytoplasm in apoptotic cells. These alterations of Sir2alpha were largely
      inhibited by a caspase-9 dominant-negative mutant or Bcl-xL. Our results indicate
      that Sir2alpha undergoes dynamic changes in caspase-dependent manner during
      apoptosis.

PMID- 17027981
TI  - Characterization of DIDS-sensitive ATP accumulation in brain synaptic vesicles.
AB  - ATP is an excitatory neurotransmitter in the central and peripheral nervous
      system. We investigated ATP accumulation in highly purified brain synaptic
      vesicles (SVs). Based on the amount of ATP accumulated in SVs under the
      conditions used, ATP is not transported against a concentration gradient but
      rather appears to have a Delta mu H(+)-independent mechanism. ATP transport was
      inhibited by DIDS and NEM, but was not affected by Mg(2+) or by pre-incubation
      with nucleotides. These results suggest a unique transport mechanism that does
      not involve exchange with other nucleotides or protons, unlike other known
      neurotransmitter transport systems.

PMID- 17027982
TI  - SECRET AGENT, an Arabidopsis thaliana O-GlcNAc transferase, modifies the Plum pox
      virus capsid protein.
AB  - The capsid protein of Plum pox virus (PPV-CP) is modified with O-linked GlcNAc (O
      GlcNAc). While Arabidopsis has two O-GlcNAc transferases, SECRET AGENT (SEC) and
      SPINDLY (SPY), previous work suggests that SEC modifies PPV-CP and that the
      modification plays a role in the infection process. Here, we show that when co
      expressed in Escherichia coli SEC modifies PPV-CP. Deletion mapping and site
      directed mutagenesis identified three threonine and a serine located near the N
      terminus of PPV-CP that are modified by SEC. Two of these threonines have
      recently been shown to be modified in virus from plants suggesting that SEC has
      the same specificity in plants and E. coli.

PMID- 17027983
TI  - Identification of the zinc binding ligands and the catalytic residue in human
      aspartoacylase, an enzyme involved in Canavan disease.
AB  - Canavan disease is an autosomal-recessive neurodegenerative disorder caused by a
      lack of aspartoacylase, the enzyme that degrades N-acetylaspartate (NAA) into
      acetate and aspartate. With a view to studying the mechanisms underlying the
      action of human aspartoacylase (hASP), this enzyme was expressed in a
      heterologous Escherichia coli system and characterized. The recombinant protein
      was found to have a molecular weight of 36 kDa and kinetic constants K(m) and
      k(cat) of 0.20 +/- 0.03 mM and 14.22 +/- 0.48 s(-1), respectively. Sequence
      alignment showed that this enzyme belongs to the carboxypeptidase metalloprotein
      family having the conserved motif H(21)xxE(24)(91aa)H(116). We further
      investigated the active site of hASP by performing modelling studies and site
      directed mutagenesis. His21, Glu24 and His116 were identified here for the first
      time as the residues involved in the zinc-binding process. In addition, mutations
      involving the Glu178Gln and Glu178Asp residues resulted in the loss of enzyme
      activity. The finding that wild-type and Glu178Asp have the same K(m) but
      different k(cat) values confirms the idea that the carboxylate group contributes
      importantly to the enzymatic activity of aspartoacylase.

PMID- 17027984
TI  - Orexin-A (hypocretin 1)-like immunoreactivity in growth hormone-containing cells
      of the Japanese seaperch (Lateolabrax japonicus) pituitary.
AB  - Immunohistochemical techniques were employed to investigate the distribution of
      orexin-A-like immunoreactivity in the Japanese seaperch (Lateolabrax japonicus)
      pituitary. Orexin-A-immunoreactive cells were concentrated in the proximal part
      of the pars distalis. We found that these cells corresponded to the cells
      immunostained with antiserum against salmon growth hormone (sGH). Immunoelectron
      microscopic analysis indicated that the orexin-A-like substance and GH coexisted
      in the secretory granules. Western blot analysis of seaperch pituitary extract
      revealed that anti-human orexin-A serum labeled approximately 16.2- and 8.0-kDa
      bands, which were not labeled with anti-sGH serum. The orexin-A-like substance in
      the pars distalis may participate in the modulation of pituitary functions
      together with GH in the seaperch.

PMID- 17027985
TI  - Methodological and ethical issues in conducting qualitative research with
      children and young people: a literature review.
AB  - BACKGROUND: There is an increasing interest in involving children in research
      that has been influenced by the recognition of children's rights and by the
      reconceptualisation of children within the social sciences as active agents
      rather than as the objects of research. OBJECTIVES: To review the methodological
      and ethical issues involved in conducting qualitative research with children and
      to consider the implications for nursing research in light of recent debates
      within the social sciences. DESIGN: Narrative literature review using a
      systematic search of computerized databases. DATA SOURCES: Published papers, key
      texts, reports and policy documents that relate to the methodological and ethical
      issues in conducting qualitative research with children. RESULTS: There are three
      ethical issues in relation to conducting research with children: power relations,
      informed consent and confidentiality. Two key methodological issues are
      identifiable in relation to conducting research with children. One is
      epistemological and relates to the different cultures of childhood and adulthood
      and the second relates to the heterogenous nature of childhood itself. Novel
      techniques and task-based activities are being increasingly used to establish
      rapport and as a method of data collection. CONCLUSION: There are both
      differences and similarities in conducting qualitative research with children and
      with adults but often the similarities have been overlooked and the differences
      overstated. Nursing and other health-related researchers conducting research with
      adults could learn much from children's researchers, particularly in terms of
      sensitivity to ethical issues. Nursing research need to consider the
      methodological issues that have been debated in the social sciences and to
      critically reflect on the use of novel techniques in qualitative research.

PMID- 17027986
TI  - Measuring peer caring behaviors of nursing students: scale development.
AB  - BACKGROUND: Caring is one of the most important domains of nursing research, peer
      caring among student nurses, and its potential effects on nurse caring behaviors
      remains largely unexplored. Few tools in the literature target peer caring
      interactions, and which were either irrelevant to our research purpose or
      culturally inappropriate for nursing student population in Taiwan. OBJECTIVES:
      The purpose of this study was to develop a culturally sensitive instrument to
      measure peer caring behavior from the student perspective and to offer a
      descriptive answer to "what is peer caring in Taiwan." DESIGN: The study uses
      both qualitative and quantitative methods in developing the "Peer Caring
      Measurement (PCM)" questionnaire. SETTINGS: Students from a 5-year associate
      degree nursing program in a university of technology in southern Taiwan were
      recruited into this study. PARTICIPANTS: Thirteen first- through fourth-year
      student volunteers between the ages of 16 and 20 were interviewed to explore
      caring behavior in student peer-to-peer interactions. Two classes from each of
      the first, second, third, and fourth year students, a total of 360 students were
      randomly selected to assess the internal consistency of "PCM", and 47 first-year
      students were conveniently selected to examine the stability of the tool.
      METHODS: Interviews were conducted in an unstructured manner. Qualitative data
      were analyzed by a constant comparative method. The questionnaire survey was used
      to assess the validity and reliability of "PCM". RESULTS: A 17-item "PCM" was
      developed; the content validity, construct validity, and reliability of the tool
      were ensured by expert review, factor analysis, and internal consistency. Three
      factors, labeled assistant caring, academic caring, and affective caring,
      accounted for 63.197% of the variance. CONCLUSIONS: The "PCM" addressed the
      multidimensional construct of peer caring. It was validated in a Chinese language
      version and can be used in college settings to evaluate student interactions and
      their peer caring behaviors.

PMID- 17027987
TI  - Calling for international collaborative research in nursing, genetics and
      genomics: a discussion paper.
AB  - There is an explosion in the numbers of nurse authors exploring new and exciting
      opportunities to understand genomic medicine because of international success on
      The Human Genome Project. OBJECTIVES: The primary purpose of this paper is to
      spotlight and to promote collaborative interdisciplinary and international
      nursing research within genetics and genomics. DESIGN: Review of the literature.
      DATA SOURCES: Research in nursing pertaining to genetics and genomics, policy
      statements, and opinion papers. REVIEW METHODS: Synthesis of the literature in
      four areas: genetic nursing research, genomic medicine, barriers to international
      collaboration, and elements that foster international collaboration. RESULTS:
      Genetics and genomic medicine have implications for virtually all diseases in all
      health care settings in developed and still developing nations. Research in
      nursing, genetics and genomics is scarce. There is a gap in nursing literature
      about how to address barriers to foster international collaboration. CONCLUSIONS:
      The authors who have engaged in international collaboration offer a tentative
      road map for establishing and assessing the progress of research collaboration.
      New funding mechanisms to support international nursing research in this area are
      needed.

PMID- 17027989
TI  - The Leishmania donovani complex: genotypes of five metabolic enzymes (ICD, ME,
      MPI, G6PDH, and FH), new targets for multilocus sequence typing.
AB  - Flagellates of the Leishmania donovani complex are causative agents of human
      cutaneous and visceral leishmaniasis. The complex is comprised of L. donovani,
      Leishmania infantum and Leishmania archibaldi, although the latter is not now
      considered to be a valid species. Morphological distinction of Leishmania species
      is impractical, so biochemical, immunological and DNA-based criteria were
      introduced. Multilocus enzyme electrophoresis (MLEE) is the present gold
      standard. We have sequenced the genes encoding five metabolic enzymes used for
      MLEE, both to resolve the DNA diversity underlying isoenzyme mobility differences
      and to explore the potential of these targets for higher resolution PCR-based
      multilocus sequence typing. The genes sequenced were isocitrate dehydrogenase,
      malic enzyme, mannose phosphate isomerase, glucose-6-phosphate dehydrogenase, and
      fumarate hydratase, for 17 strains of L. infantum, seven strains of L. donovani,
      and three strains of L. archibaldi. Protein mobilities predicted from amino acid
      sequences did not always accord precisely with reported MLEE profiles. A high
      number of heterozygous sites was detected. Heterozygosity was particularly
      frequent in some strains and indirectly supported the presence of genetic
      exchange in Leishmania. Phylogenetic analysis of a concatenated alignment based
      on a total of 263 kb protein-coding sequences showed strong correlation of
      genotype with geographical origin. Europe and Africa appear to represent
      independent evolutionary centres.

PMID- 17027990
TI  - Spatial and temporal transmission risk of Dirofilaria immitis in Argentina.
AB  - The aim of this work was to assess spatial and seasonal Dirofilaria immitis
      transmission risk throughout Argentina with models based on the temperature
      threshold below which filarial development will not proceed in the mosquito (i.e.
      14 degrees C), the occurrence and the number of potential vector mosquito
      species, and the Heartworm Development Units derived from the degree-days
      concept. The four models showed a similar increasing southwest-northeast tendency
      and correlated significantly with canine prevalences used as external validation
      data. About one-third of Argentina would be suitable for heartworm transmission
      and the highest risk areas include the north-eastern provinces. According to our
      models, heartworm transmission is markedly seasonal with peaks in January and
      February; no region would support transmission throughout the year. To improve
      the present models, it is necessary to know which mosquito species are competent
      rather than potential vectors in the country. We believe the present study
      provides the first risk assessment maps for D. immitis transmission in the
      Southern Hemisphere and provides a useful guide for heartworm prevention during
      the transmission periods in different regions of Argentina.

PMID- 17027988
TI  - The neurocognitive bases of human multimodal food perception: consciousness.
AB  - This review explores how we become aware of the (integrated) flavor of food. In
      recent years, progress has been made understanding the neural correlates of
      consciousness. Experimental and computational data have been largely based on the
      visual system. Contemporary neurobiological frameworks of consciousness are
      reviewed, concluding that neural reverberation among forward- and back-projecting
      neural ensembles across brain areas is a common theme. In an attempt to
      extrapolate these concepts to the oral-sensory and olfactory systems involved
      with multimodal flavor perception, the integration of the sensory information of
      which into a flavor gestalt has been reviewed elsewhere (Verhagen, J.V., Engelen,
      L., 2006. The neurocognitive bases of human multimodal food perception: Sensory
      integration. Neurosci. Biobehav. Rev. 30(5): 613_650), I reconceptualize the
      flavor-sensory system by integrating it into a larger neural system termed the
      Homeostatic Interoceptive System (HIS). This system consists of an oral (taste,
      oral touch, etc.) and non-oral part (non oral-thermosensation, pain, etc.) which
      are anatomically and functionally highly similar. Consistent with this new
      concept and with a large volume of experimental data, I propose that awareness of
      intraoral food is related to the concomitant reverberant self-sustained
      activation of a coalition of neuronal subsets in agranular insula and
      orbitofrontal cortex (affect, hedonics) and agranular insula and perirhinal
      cortex (food identity), as well as the amygdala (affect and identity) in humans.
      I further discuss the functional anatomy in relation essential nodes. These
      formulations are by necessity to some extent speculative.

PMID- 17027991
TI  - Activation of extracellular signal-regulated kinase signaling by chronic
      electroconvulsive shock in the rat frontal cortex.
AB  - The effects of chronic electroconvulsive shock (ECS), given daily for 1, 5 and 10
      days, on the activation of extracellular signal-regulated kinase (ERK) were
      studied in the rat frontal cortex. The phosphorylation of MEK1/2 and ERK1/2
      increased through 5 days of ECS. Thereafter, a plateau was achieved. The
      expression of brain-derived neurotrophic factor was continuously increased for 10
      days. Our data show that the effect of ECS on ERK1/2 signaling is increased with
      chronic treatment.

PMID- 17027992
TI  - Diagonal ear-lobe crease is associated with carotid intima-media thickness in
      subjects free of clinical cardiovascular disease.
AB  - BACKGROUND: The diagonal ear-lobe crease (ELC) has been suggested as a simple
      marker of cardiovascular disease in the general population. There is no knowledge
      concerning the relation between carotid intima-media thickness (IMT), an index of
      subclinical atherosclerosis, and diagonal ELC. The aim of our study was to assess
      this relation. METHODS AND RESULTS: The study population was prospectively
      selected from apparently healthy subjects. Sixty-five consecutive subjects with
      ELC and 65 age- and gender-matched control subjects without ELC were included in
      this study. These were examined by B-mode ultrasound to measure the IMT at the
      far wall of the common carotid artery. Subjects with ELC had significantly higher
      carotid IMT compared to control subjects without ELC (0.88+/-0.14 versus 0.69+/
      0.14 mm, respectively, p=0.0001). The presence of ELC was independently
      associated with IMT in the multivariate logistic regression analysis. In
      addition, we detected a significant positive correlation between the presence of
      ELC and carotid IMT (r=0.558, p=0.0001). CONCLUSIONS: We have shown for the first
      time an association between increased carotid IMT and diagonal ELC in apparently
      healthy subjects.

PMID- 17027993
TI  - Movement of a spherical cell in capillaries using a boundary element method.
AB  - This study aims to investigate the translation and rotation of a spherical
      particle in capillaries and overcomes limitations in previous studies by using a
      boundary element method. The capillary, a straight cylindrical tube, is filled
      with a Newtonian viscous fluid. A spherical particle is arbitrarily positioned in
      the capillary either co-centrically or eccentrically and is free to translate and
      rotate. Flow in the capillary is first assumed to be caused solely by the
      movement of the sphere under the gravity. When a steady state is reached, the net
      force and torque on the sphere are zero. The translating velocity and rotation of
      the particle are calculated from equilibrium equations. For a co-centric sphere,
      our result agrees to Bohlin's analytical solution (Bohlin, 1960) and the
      difference is less than 1%. For an eccentrically positioned sphere in the tube,
      there are no analytical solutions unless the eccentricity is infinitesimal.
      Results by boundary element method (BEM) give an improved estimations on the
      velocity and rotation of the sphere than earlier results by a boundary
      singularity method (BSM), particularly when the clearance between the tube and
      the sphere becomes small. Movement of a spherical particle in a capillary driven
      by a pressure gradient is further investigated, which has closer relevance to
      movement of blood cells in capillaries. The current study using BEM enables
      investigation on cell movement in close proximities of the capillary wall.

PMID- 17027994
TI  - A functional comparison of canine and murine bone marrow derived cultured mast
      cells.
AB  - Disorders involving mast cells are extremely common in dogs, ranging from
      allergic diseases to neoplastic transformation resulting in malignant mast cell
      tumors. Relatively little is known regarding the basic biologic properties of
      normal canine mast cells, largely due to the difficulty in reliably purifying
      large numbers from canine skin. In vitro generated bone marrow derived cultured
      mast cells (BMCMCs) are routinely used in both human and murine studies as a
      ready source of material for in vitro and in vivo studies. We previously
      developed a technique to generate canine BMCMCs from bone marrow derived CD34+
      cells and demonstrated that these cells exhibit the phenotypic properties
      characteristic of mast cells and release histamine in response to IgE cross
      linking. The purpose of the following study was to characterize the functional
      properties of these canine BMCMCs and contrast these with the functional
      properties of murine BMCMCs. Our work demonstrates that both IL-4 and IL-10
      promote canine BMCMC proliferation, possibly through upregulation of Kit
      expression, while TGFbeta inhibits proliferation. The canine BMCMCs produce a
      variety of cytokines and chemokines in response to IgE cross-linking and chemical
      stimulation including IL-3, IL-4, IL-13, GM-CSF, RANTES, and MIP1alpha.
      Interestingly, the canine BMCMCs released significantly larger amounts of MCP-1
      and tryptase and significantly smaller amounts of IL-6 following chemical
      stimulation and IgE cross-linking when compared to murine BMCMCs. Lastly, the
      canine BMCMCs produced larger amounts of active MMP9 than their murine
      counterparts. In summary, canine BMCMCs exhibit unique functional properties that
      distinguish them from murine BMCMCs and provide insight into the contribution of
      these cells to mast cell disorders in the dog.

PMID- 17027995
TI  - Factorial design applied to a non-aqueous capillary electrophoresis method for
      the separation of beta-agonists.
AB  - The aim of this work was to study the effects of both chemical and instrumental
      parameters on the separation of beta-agonists (clenbuterol (CLE), salbutamol
      (SAL) and terbutaline (TER)) by non-aqueous capillary electrophoresis (NACE)
      method. Due to the number of parameters involved and their interactions,
      factorial experimental designs (EDs) at two levels was applied to investigate the
      influence of experimental factors (ionic strength of the background electrolyte
      (BGE), organic solvent, injection time, voltage and temperature) in sets of
      several CE responses (resolution, (RS), number of theoretical plate (N), tailing
      factor (TF) and migration time (tm)). As a compromise between the four responses,
      the optimum condition was obtained in 18 mM ammonium acetate in methanol
      (MeOH):acetonitrile (ACN):glacial acetic acid (66:33:1%, v/v/v) using an
      injection time of 4 s, the voltage and the temperature of 28 kV and 24 degrees C,
      respectively. The proposed NACE permitted the baseline separation of the three
      beta-agonists within 10.5 min with good repeatability (%RSD < 3.5%) and linearity
      (r2 > 0.99). The developed method was applicable for the analysis of the beta
      agonists in syrup and tablets and the NACE condition was compatible with a mass
      spectrometer detector.

PMID- 17027996
TI  - Simple and environmental friendly procedure for the gas chromatographic-mass
      spectrometric determination of caffeine in beverages.
AB  - A simple, quick and organic solvent saving procedure has been developed for the
      GC/MS determination of caffeine in beverages. The procedure involves the mixing
      of 25 microL sample with 1 mL ethyl acetate, and a following simple desiccation
      procedure in a 1.5 mL autosampler vial. A linear calibration curve was generated
      with caffeine concentration ranging from 0.005 mg/L to 30.0mg/L. The procedure
      developed provides a 0.001 mg/L detection limit of caffeine in the final solution
      by injection of 1 microL solution and the relative standard deviation (RSD) was
      less than 2% for independent measurement. The total amount of organic solvent
      used for individual detection is 1 mL of nontoxic ethyl acetate. The developed
      method was repeatable and could be applied to determine trace amounts of caffeine
      in popular commercial beverages.

PMID- 17027997
TI  - Improved and simplified liquid chromatography/atmospheric pressure chemical
      ionization mass spectrometry method for the analysis of underivatized free amino
      acids in various foods.
AB  - An improved analytical method which offers rapid, accurate determination and
      identification of 22 amino acids in a variety of matrices, e.g. baby foods,
      juices, honey is reported. The amino acids were extracted from the matrixes using
      acidified water. Simultaneous determination of 22 underivatized amino acids was
      carried out by a liquid chromatography-mass spectrometry (LC/MS). A narrow-bore
      column allowed rapid screening and quantitative analysis by positive
      LC/atmospheric pressure chemical ionization (APCI) MS with only acidified mobile
      phase. Retention times of the 22 amino acids were in the range of ca. 0.9-7.5
      min. Sample preparation without clean-up followed by fast chromatographic
      analysis allowed the analysis to be completed in <25 min.

PMID- 17027998
TI  - Chromatographic separation of certain metal ions using a bifunctional quaternary
      ammonium-sulfonate mixed bed ion-exchanger.
AB  - The separation behaviour of Pb(2+), Cu(2+), Cd(2+), Co(2+), Zn(2+) and Ni(2+) on
      bifunctional quaternary ammonium-sulfonate mixed ion-exchangers (Dionex, IonPac
      CS5 and CG5) was studied using different eluents including solutions of oxalic
      acid, potassium oxalate, sodium oxalate and ammonium oxalate. Separated metal
      ions were followed by using 4-(2-pyridylazo) resorcinol (PAR) as post-colouring
      complex. The retention factors of different ions proved to be dependent on the
      pH, concentration, nature of each complexing agent, and to less extent on eluent
      flow rate. The retention behaviour and separation mechanism of complexed metal
      analytes are discussed in the light of the stability of metal complexes and the
      ligand complexing ability of used eluent. Comparison between various mobile
      phases is evaluated, and both sodium and potassium oxalate can be used
      successfully for simultaneous separation of studied metals with good resolution
      within short elution periods. The method can be used in different applications
      including analysis of bottled water from different resources.

PMID- 17027999
TI  - 4-(4'-Methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide: a new
      electrophoric derivatizing reagent.
AB  - Commercially-available 4,4'-dimethyloctafluorobiphenyl was converted in a single
      step to 4-(4'-methyltetrafluorophenyl)-2,3,5,6-tetrafluorobenzyl bromide (MTFP
      TFBBr) for the purpose of providing a new electrophoric derivatizing reagent.
      When reacted with this reagent, 2-fluoro-O6-(2'-hydroxyethyl)hypoxanthine, a
      model analyte, gave a mixture of isomeric products (apparently substituted at N7
      and N9, analogous to its known reaction with pentafluorobenzyl bromide), and 53
      femtograms of the mixture was detected at S/N = 10 by gas chromatography electron
      capture mass spectrometry (GC-EC-MS). As intended, the volatility of the MTFB
      TFBBr derivative was much less (two-fold) than that of the corresponding
      pentafluorobenzyl derivative. It is anticipated that MTFB-TFBBr sometimes will be
      useful in providing an electrophoric derivative that encounters less background
      noise in analysis by electrophore derivatization/GC-EC-MS.

PMID- 17028000
TI  - Classification and dating of black gel pen ink by ion-pairing high-performance
      liquid chromatography.
AB  - A novel approach for classification and dating of the black gel pen ink entries
      on document was developed based on ion-pairing high-performance liquid
      chromatography (IP-HPLC). Ninety-three black gel pens were collected and divided
      into two groups, dye-based and pigment-based, by preliminary solubility test. The
      chromatographic conditions for separation of the dye-based black gel pen inks
      were optimized and the dye components in inks were satisfactorily separated by
      using 40 mmol/L tetrabutylammonium bromide as ion-pairing reagent. According to
      the number and the chromatographic retention times of the main dye components,
      the 50 dye-based inks were categorized into four classes. The inks within a class
      can be further identified by the percentage of each dye component. The
      compositional changes of the dye components in the black gel pen ink entries on
      paper were investigated in light and natural aging conditions and it has been
      found that the dye components in the ink entries underwent obvious decomposition,
      and the decomposing extent of the dye components was related to the aging time.
      The results can provide scientific evidences for dating of the suspicious black
      gel pen ink entries on documents.

PMID- 17028001
TI  - Rapid determination of short chain carnitines in human plasma by electrospray
      ionisation-ion trap mass spectrometry using capillary electrophoresis instrument
      as sampler.
AB  - A capillary electrophoresis apparatus was used as sampler for flow injection
      analysis (FIA) in tandem mass spectrometry of L-carnitine and its acetyl- and
      propionyl-metabolites in human plasma. The capillary electrophoresis instrument
      was coupled to the ion trap mass spectrometer by an electrospray ionization
      coaxial sheath liquid interface. The electrophoresis capillary introduced the
      sample directly into the source by applying a prolonged sample injection. The use
      of the capillary electrophoresis apparatus miniaturised the FIA procedure,
      substantially reducing the quantities of solvents and samples used, and allowed
      rapid automated sequential analyses. The method was optimised and validated using
      a dialyzed human plasma matrix. The plasma samples were analysed after a simple,
      rapid deproteinisation procedure with acetonitrile and diluted 70 times before
      direct injection into the mass spectrometer for product ion scan MS/MS analysis
      in positive ionisation. The total analysis time was 5 min, including capillary
      preconditioning and acquisition time (3 min). The method was sensitive, allowing
      the determination of L-, L-acetyl- and L-propionyl-carnitines at 140, 14 and 3.6
      nM concentrations (injected values) corresponding to lower limit of quantitation
      values in plasma of 10, 1 and 0.25 microM, respectively. The method was processed
      for full validation and applied to the analysis of L-carnitine and its short
      chain derivatives in human plasma samples.

PMID- 17028002
TI  - Activational levels of androgens influence risk assessment behaviour but do not
      influence stress-induced suppression in hippocampal cell proliferation in adult
      male rats.
AB  - Adult male, but not female, rats demonstrate a suppression in hippocampal cell
      proliferation in response to an acute predator odour stress. The present study
      examined the effect of activational levels of androgens on stress-induced changes
      in hippocampal cell proliferation and defensive and non-defensive behaviours in
      adult male rats. Adult male Sprague-Dawley rats were castrated and exposed to
      trimethylthiazoline (TMT, the main component of fox feces). Androgen status did
      not significantly affect TMT-induced suppression in hippocampal cell
      proliferation or expression of defensive burying. However, castrated males did
      not show an increase in duration of stretch attends (a risk assessment behaviour)
      in response to TMT. The results of this study suggest that activational levels of
      androgens in the male rat do not directly regulate the sex difference in stress
      induced suppression of hippocampal cell proliferation but do regulate risk
      assessment behaviour.

PMID- 17028003
TI  - Nozzle and liquid effects on the spray modes in nanoelectrospray.
AB  - Unforced nanoelectrospray can exhibit a number of stable spray modes. These
      include low frequency pulsations, high frequency pulsations, and a steady cone
      jet. Experiments are reported here on such pulsations that have been observed in
      various salt loaded solutions of ethylene glycol, triethylene glycol and water.
      The spray current was monitored with 1 mus time resolution to show that spray
      regime characteristics depend on nozzle diameter and liquid conductivity. The
      frequency of pulsations was found to increase with both increased liquid
      conductivity and decreasing nozzle diameter. The charge ejected during a pulse is
      lower for smaller nozzles spraying higher conductivity liquids. Water solutions
      were observed undergoing high frequency pulsations, with these pulsations often
      occurring in lower frequency bursts. The frequencies of water pulsations were as
      high as 635 kHz but the charge ejected by each pulsation was an order of
      magnitude lower than that observed in triethylene glycol. An unforced
      electrospray of water was also identified as being in the steady cone-jet mode
      with a higher degree of confidence than previously. The values for stable
      pulsation frequency and charge ejected observed in ethylene glycol lay between
      those of TEG and water.

PMID- 17028004
TI  - Microwave-assisted synthesis of anhydrous CdS nanoparticles in a water-oil
      microemulsion.
AB  - Microwave irradiation at a frequency of 2.45 GHz and a power ranging between 22
      and 30 W was used, in a water-oil microemulsion at 35+/-2 degrees C, to obtain
      stable, small, crystalline, anhydrous CdS nanoparticles exhibiting enhanced
      luminescence properties. The process of nanoparticles growth at different
      irradiation times was followed by UV-vis spectroscopy. It was observed that
      irradiated nanoparticles grew faster and their size reached a constant value. The
      final mean nanoparticle diameter was 2.7 nm, smaller than that observed in a non
      irradiated sample, in which particle dimensions slowly increased even after 10 h.
      This finding was confirmed by high resolution transmission electron microscopy
      which also suggested that the spherical nanoparticles had a narrow size
      distribution and were spatially well separated. Furthermore, Fourier transform
      infrared spectroscopy was used to obtain information about structural changes
      that the microemulsion underwent when irradiated by microwaves. In particular,
      the evolution of the stretching and bending bands of water molecules along with
      the CO and SO3 stretching bands of the surfactant molecules, showed that water
      was selectively and almost completely extracted from the aqueous core of the
      reversed micelles. Changes in the surroundings of the nanoparticles surface were
      monitored by photoluminescence spectroscopy and variations in the emission band
      profiles indicated enhanced luminescence properties. The latter finding, as well
      as the inhibition of the nanoparticles growth process, are attributable to the
      progressive reduction of water content in the core of the reversed micelles.

PMID- 17028006
TI  - Application of a multi-dentate amphiphilic compound to transfer silver
      nanoparticles into an organic solvent.
AB  - A multi-dentate amphiphilic compound, 3,3'-(dodecylazanediyl)-bis-[N-(2
      aminoethyl)propanamide] (12C-2NH2) has been synthesized. The molecular structure
      was characterized by Fourier transform infrared (FT-IR) spectroscopy, ultraviolet
      visible (UV-vis) spectra, nuclear magnetic resonance (NMR) spectra, and fast atom
      bombardment mass (FAB-MS) spectra. 12C-2NH2 was employed to stabilize silver
      nanoparticles. Surface properties and stability of silver nanoparticles were
      controlled by adjusting the 12C-2NH2 to silver (0) molar ratio. 12C-2NH2 was also
      applied to transfer silver nanoparticles from an aqueous to an organic phase. The
      transfer efficiency depends on 12C-2NH2 concentration. When 12C-2NH2 to silver
      (0) molar ratio was 2:1, the highest efficiency of phase transfer to toluene was
      obtained. These 12C-2NH2 stabilized silver nanoparticles are very stable over a
      period of four days in toluene.

PMID- 17028005
TI  - Quartz crystal microbalance studies on bilirubin adsorption on self-assembled
      phospholipid bilayers.
AB  - Bilirubin adsorption on self-assembled phospholipid bilayers was studied using
      quartz crystal microbalance, and factors influencing its adsorption such as pH,
      temperature, and solution ionic strength were discussed in detail. The results
      show the amount of adsorbed bilirubin on self-assembled phospholipid bilayers is
      small at higher temperature and large at higher pH and solution ionic strength,
      and the adsorption kinetic parameter estimated from the in situ frequency
      measurement is (1.8+/-0.27)x10(6) M(-1) (mean +/- S.D.). With the present method,
      the desorption of adsorbed bilirubin caused by human serum albumin and the
      photoinduced decomposition of adsorbed bilirubin under light illumination were
      also examined. QCM measurement provides a useful method for monitoring the
      adsorption/desorption process of bilirubin on self-assembled phospholipid
      bilayers.

PMID- 17028007
TI  - Solvent effect on CO oxidation as a novel diagnosing tool to pin down low
      coverage CO at the liquid-solid interface: An in situ infrared study.
AB  - In situ probing of liquid-solid interfaces is important for understanding
      heterogeneous liquid-phase catalysis and other interfacial phenomena, but the
      spectroscopic interference from the bulk is often a problem. Some organics may
      have infrared features overlapping the adsorbed CO peaks, making the
      determination of adsorbed CO difficult. In this study, CCl4-flushing was used as
      a novel diagnosing tool to pin down the low-coverage CO derived from
      decarbonylation of organics. This diagnosing tool was designed based on our in
      situ reflection-absorption infrared spectroscopy results reported here that there
      is a marked solvent effect (water > ethanol > methanol > cyclohexane > benzene
      approximately carbon tetrachloride) on CO oxidation at the liquid-solid
      interface. Possible reasons for that solvent effect were discussed.

PMID- 17028008
TI  - Differentiation of Leishmania major is impaired by over-expression of
      pyroglutamyl peptidase I.
AB  - Pyroglutamyl peptidases I (PPI) are cysteine peptidases of the clan CF, family
      C15, which hydrolyse N-terminal l-pyroglutamyl residues (l-pGlu). The l-pGlu
      modification is a post-transcriptional modification that confers relative
      aminopeptidase resistance and, in some cases, is essential to the modified
      peptides' biological activity. PPIs have been identified in a variety of
      organisms, although definitive biological functions have yet to be attributed to
      them. The L. major PPI was expressed in Escherichia coli as active recombinant
      enzyme, and shown to have biochemical properties more similar to mammalian than
      bacterial PPIs. The LmPPI active site catalytic triad of E101, C210, and H234 was
      confirmed by mutagenesis. PPI activity was detected in L. major promastigotes,
      and the enzyme localised to the parasite cytosol. No detectable phenotype could
      be observed for L. major PPI-deficient mutants, which retained infectivity to
      macrophages in vitro and mice. However, over-expression of the active PPI, but
      not inactive PPI(C210A), in L. major impaired differentiation from the procyclic
      promastigote to the infective metacyclic promastigote. Susceptibility to a
      natural l-pGlu-modified antimicrobial peptide, gomesin, was tested using the
      different cell lines, which were all equally susceptible. Whilst PPI is
      widespread through the eukaryotic kingdom, this study now suggests that the
      enzyme is not essential for normal eukaryotic cell function. However, PPI could
      be involved in regulating the action of l-pGlu-modified peptides required for
      differentiation of L. major.

PMID- 17028009
TI  - Involvement of actin and myosins in Plasmodium berghei ookinete motility.
AB  - Ookinetes of the genus Plasmodium are motile, invasive cells that develop in the
      mosquito midgut following ingestion of a parasite-infected blood meal. We show
      here that ookinetes display gliding motility on glass slides in the presence of
      insect cells. Moreover, in addition to stationary "flexing" and "twirling" of the
      cells, two distinct types of movements occur: productive forward translocational
      motility in straight segment that progresses with an average speed of
      approximately 6mum/min and rotational motility, which does not lead to forward
      translocation. Locomotion is reduced by treatment with butanedione monoxime, an
      inhibitor of myosin ATPase, and by three different actin inhibitors. We also
      studied the expression during ookinete development of genes encoding actin and
      two small class XIV myosins, PbMyoA, and PbMyoB. Western immunoblots revealed
      that PbMyoA is only present in fully mature ookinetes, whilst the other two
      proteins are additionally expressed in gametocytes and zygotes.
      Immunofluorescence experiments reveal that MyoA and actin co-localize in the
      apical tip of the parasite whereas MyoB displays a punctate pattern of expression
      around the entire cell periphery. Following treatment with jasplakinolide, the
      apparent level of detectable actin appears to substantially increase and becomes
      concentrated in a discrete area in the basal pole of the ookinete.

PMID- 17028010
TI  - Central actions of angiotensin II on spontaneous baroreflex sensitivity in the
      trout Onc orhynchus mykiss.
AB  - The goal of the present study was to investigate the central action of native
      angiotensin II (ANG II) on the spontaneous baroreflex sensitivity (BRS) in
      unanesthetized trout. The animals were equipped with two subcutaneous
      electrocardiographic (ECG) electrodes, a dorsal aorta catheter and an
      intracerebroventricular (ICV) cannula which was inserted within the third
      ventricle of the brain. The ECG and the systolic blood pressure (SBP) signals
      were recorded during a pre-injection period of 5 min and during five post
      injection periods of 5 min. All injections were made at the fifth minute of the
      test. The time-series were processed with a sequence technique in order to detect
      the sequences of three or more consecutive increases in the SBP pulse, or three
      or more decreases in the SBP pulse correlated respectively with one delay beat
      increase of the RR interval of the ECG signal or shortening of this interval. The
      slope of the average regression line between the SBP and the RR intervals for
      each type of sequence was taken as a measure of the spontaneous BRS. Compared
      with pre-injection values, the ICV injection of vehicle (0.5 microl) had no
      effect on heart rate (HR), SBP, the total number of positive or negative
      sequences or on the spontaneous BRS during the post-injection periods. By
      contrast, ANG II at doses of 5 and 50 pmol increased HR but only 50 pmol ANG II
      elevated SBP. For all doses, ANG II depressed the spontaneous BRS, but the
      peptide had no effect upon the number of each baroreflex sequences. Intra
      arterial injections of atropine dramatically reduced the number of positive and
      negative baroreflex sequences and decreased the sensitivity of the few remaining
      sequences, suggesting that the autonomic control of the cardiac BRS was solely
      due to vagal parasympathetic control. In atropinized trout the ICV injection of 5
      pmol ANG II had no effect upon HR, SBP and the baroreflex parameters. This study
      determines for the first time the spontaneous BRS in a non-mammalian species and
      demonstrates an inhibitory action of ICV injection of ANG II upon this variable
      through a probable control of the vagal parasympathetic activity.

PMID- 17028011
TI  - Peroxisomal beta-oxidation--a metabolic pathway with multiple functions.
AB  - Fatty acid degradation in most organisms occurs primarily via the beta-oxidation
      cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes,
      whereas plants and most fungi harbor the beta-oxidation cycle only in the
      peroxisomes. Although several of the enzymes participating in this pathway in
      both organelles are similar, some distinct physiological roles have been
      uncovered. Recent advances in the structural elucidation of numerous mammalian
      and yeast enzymes involved in beta-oxidation have shed light on the basis of the
      substrate specificity for several of them. Of particular interest is the
      structural organization and function of the type 1 and 2 multifunctional enzyme
      (MFE-1 and MFE-2), two enzymes evolutionarily distant yet catalyzing the same
      overall enzymatic reactions but via opposite stereochemistry. New data on the
      physiological roles of the various enzymes participating in beta-oxidation have
      been gathered through the analysis of knockout mutants in plants, yeast and
      animals, as well as by the use of polyhydroxyalkanoate synthesis from beta
      oxidation intermediates as a tool to study carbon flux through the pathway. In
      plants, both forward and reverse genetics performed on the model plant
      Arabidopsis thaliana have revealed novel roles for beta-oxidation in the
      germination process that is independent of the generation of carbohydrates for
      growth, as well as in embryo and flower development, and the generation of the
      phytohormone indole-3-acetic acid and the signal molecule jasmonic acid.

PMID- 17028012
TI  - Peroxisomal matrix protein receptor ubiquitination and recycling.
AB  - The peroxisomal targeting signal type1 (PTS1) receptor Pex5 is required for the
      peroxisomal targeting of most matrix proteins. Pex5 recognises target proteins in
      the cytosol and directs them to the peroxisomal membrane where cargo is released
      into the matrix, and the receptor shuttles back to the cytosol. Recently, it has
      become evident that the membrane-bound Pex5 can be modified by mono- and
      polyubiquitination. This review summarises recent results on Pex5 ubiquitination
      and on the role of the AAA peroxins Pex1 and Pex6 as dislocases required for the
      release of Pex5 from the membrane to the cytosol where the receptor is either
      degraded by proteasomes or made available for another round of protein import
      into peroxisomes.

PMID- 17028013
TI  - p120-ctn: A nexus for contextual signaling via Rho GTPases.
AB  - p120 catenin (p120) is the prototypic member of a subfamily of armadillo repeat
      domain proteins involved in intercellular adhesion. Recent evidence indicates
      that p120 associates with classical cadherins and regulates their stability.
      Ectopic p120 expression results in a variety of morphological effects, and
      promotes cell migration. There is now strong evidence that p120 acts, at least in
      part, through regulation of Rho GTPases. The data suggest that p120 may act as a
      signaling nexus, conveying messages from the cellular micro- and macro
      environment to the cell's interior. By regulating Rho GTPases in a context
      dependent manner p120 can exert profound effects on cellular responses from
      synaptic plasticity to vesicle trafficking, as well as regulate the motile vs.
      sessile, and possibly the proliferative vs. quiescent phenotype of epithelial
      cells. Here, we review the new evidence on the relationship of p120 to Rho
      GTPases, and discuss potential roles for the p120-Rho connection in normal and
      malignant cells.

PMID- 17028014
TI  - PTS2 co-receptors: diverse proteins with common features.
AB  - One feature of the PTS2 import pathway is the separation of the roles of the PTS
      receptor between two proteins. Pex7p alone is insufficient to act as the receptor
      for the import cycle for peroxisomal matrix proteins. In all cases, Pex7p needs a
      PTS2 co-receptor to form an import-competent PTS2 receptor complex together with
      the PTS2 cargo. We provide an overview of the proteins that have been identified
      as PTS2 co-receptors and discuss their proposed functions.

PMID- 17028015
TI  - Detection of allergens from Alternaria alternata by gold-conjugated anti-human
      IgE and field emission scanning electron microscopy.
AB  - Fungal allergens are present in viable and non-viable conidia, hyphae and fungal
      fragments. It has been shown that large quantities of allergen are released from
      conidia during germination. We used a gold immunolabelling technique and field
      emission scanning electron microscopy to examine the allergen release from
      Alternaria alternata conidia. Immunolabelling was associated with the hyphal tip
      and amorphous matter associated with the emerging hyphae. Non-specific antibody
      controls showed no labelling associated with germinating fungi. This suggests
      that material released from hyphae may be an additional source of fungal
      allergens.

PMID- 17028017
TI  - Reversal of supra-systemic pulmonary pressures following mitral valve surgery in
      a young girl.

PMID- 17028016
TI  - Octopamine and tyramine influence the behavioral profile of locomotor activity in
      the honey bee (Apis mellifera).
AB  - The biogenic amines octopamine and tyramine are believed to play a number of
      important roles in the behavior of invertebrates including the regulation of
      motor function. To investigate the role of octopamine and tyramine in locomotor
      behavior in honey bees, subjects were injected with a range of concentrations of
      octopamine, tyramine, mianserin or yohimbine. Continuous observation of freely
      moving worker bees was used to examine the effects of these treatments on the
      amount of time honey bees spent engaged in different locomotor behaviors such as
      walking, grooming, fanning and flying. All treatments produced significant shifts
      in behavior. Decreases in time spent walking and increases in grooming or stopped
      behavior were observed for every drug. However, the pattern of the shift depended
      on drug, time after injection and concentration. Flying behavior was
      differentially affected with increases in flying seen in octopamine treated bees,
      whereas those receiving tyramine showed a decrease in flying. Taken together,
      these data provide evidence that octopamine and tyramine modulate motor function
      in the honey bee perhaps via interaction with central pattern generators or
      through effects on sensory perception.

PMID- 17028018
TI  - Levosimendan in acute decompensation of anthracycline-induced cardiotoxicity.

PMID- 17028019
TI  - Serpin1 of Arabidopsis thaliana is a suicide inhibitor for metacaspase 9.
AB  - Metacaspases are distant relatives of animal caspases found in plants, fungi and
      protozoa. We demonstrated previously that two type II metacaspases of Arabidopsis
      thaliana, AtMC4 and AtMC9 are Arg/Lys-specific cysteine-dependent proteases. We
      screened a combinatorial tetrapeptide library of 130,321 substrates with AtMC9.
      Here, we show that AtMC9 is a strict Arg/Lys-specific protease. Based on the
      position-specific scoring matrix derived from the substrate library results, the
      tetrapeptide Val-Arg-Pro-Arg was identified as an optimized substrate. AtMC9 had
      a kcat/KM of 4.6x10(5) M-1 s-1 for Ac-Val-Arg-Pro-Arg-amido-4-methyl-coumarin,
      representing a more than 10-fold improvement over existing fluorogenic
      substrates. A yeast two-hybrid screen with catalytically inactive AtMC9 as bait
      identified a serine protease inhibitor, designated AtSerpin1, which was found to
      be a potent inhibitor of AtMC9 activity in vitro through cleavage of its reactive
      center loop and covalent binding to AtMC9. On the basis of the substrate
      profiling of AtMC9 and confirmation through site-directed mutagenesis, the
      inhibitory P4-P1 cleavage site of AtSerpin1 was determined to be Ile-Lys-Leu
      Arg351. Further mutagenesis of the AtSerpin1 inhibitory cleavage site modulated
      AtMC9 inhibition positively or negatively. Both AtMC9 and AtSerpin1 were
      localized in the extracellular space, suggesting an in vivo interaction as well.
      To our knowledge, this is the first report of plant protease inhibition by a
      plant serpin.

PMID- 17028021
TI  - SOS repair and DNA supercoiling influence the genetic stability of DNA triplet
      repeats in Escherichia coli.
AB  - Molecular mechanisms responsible for the genetic instability of DNA trinucleotide
      sequences (TRS) account for at least 20 human hereditary disorders. Many aspects
      of DNA metabolism influence the frequency of length changes in such repeats.
      Herein, we demonstrate that expression of Escherichia coli SOS repair proteins
      dramatically decreases the genetic stability of long (CTG/CAG)n tracts contained
      in plasmids. Furthermore, the growth characteristics of the bacteria are affected
      by the (CTG/CAG)n tract, with the effect dependent on the length of the TRS. In
      an E. coli host strain with constitutive expression of the SOS regulon, the
      frequency of deletions to the repeat is substantially higher than that in a
      strain with no SOS response. Analyses of the topology of reporter plasmids
      isolated from the SOS+ and SOS- strains revealed higher levels of negative
      supercoiling in strains with the constitutively expressed SOS network. Hence, we
      used strains with mutations in topoisomerases to examine the effect of DNA
      topology upon the TRS instability. Higher levels of negative DNA supercoiling
      correlated with increased deletions in long (CTG/CAG)n, (CGG/CCG)n and
      (GAA/TTC)n. These observations suggest a link between the induction of bacterial
      SOS repair, changes in DNA topology and the mechanisms leading to genetic
      instability of repetitive DNA sequences.

PMID- 17028020
TI  - In meso structure of the cobalamin transporter, BtuB, at 1.95 A resolution.
AB  - Crystals of the apo form of the vitamin B12 and colicin receptor, BtuB, that
      diffract to 1.95 A have been grown by the membrane-based in meso technique. The
      structure of the protein differs in several details from that of its counterpart
      grown by the more traditional, detergent-based (in surfo) method. Some of these
      differences include (i) the five N-terminal residues are resolved in meso, (ii)
      residues 57-62 in the hatch domain and residues 574-581 in loop 21-22 are
      disordered in meso and are ordered in surfo, (iii) residues 278-287 in loop 7-8
      are resolved in meso, (iv) residues 324-331 in loop 9-10, 396-411 in loop 13-14,
      442-458 in loop 15-16 and 526-541 in loop 19-20 have large differences in
      position between the two crystal forms, as have residues 86-96 in the hatch
      domain, and (v) the conformation of residues 6 and 7 in the Ton box (considered
      critical to signal transduction and substrate transport) are entirely different
      in the two structures. Importantly, the in meso orientation of residues 6 and 7
      is similar to that of the vitamin B12-charged state. These data suggest that the
      "substrate-induced" 180 degrees -rotation of residues 6 and 7 reported in the
      literature may not be a unique signalling event. The extent to which these
      findings agree with structural, dynamic and functional insights gleaned from site
      directed spin labelling and electron paramagnetic resonance measurements is
      evaluated. Packing in in meso grown crystals is dense and layered, consistent
      with the current model for crystallogenesis of membrane proteins in lipidic
      mesophases. Layered packing has been used to locate the transmembrane hydrophobic
      surface of the protein. Generally, this is consistent with tryptophan, tyrosine,
      lipid and CalphaB-factor distributions in the protein, and with predictions based
      on transfer free energy calculations.

PMID- 17028022
TI  - ATP synthase b subunit dimerization domain: a right-handed coiled coil with
      offset helices.
AB  - The dimerization domain of Escherichia coli ATP synthase b subunit forms an
      atypical parallel two-stranded coiled coil. Sequence analysis reveals an 11
      residue abcdefghijk repeat characteristic of right-handed coiled coils, but no
      other naturally occurring parallel dimeric structure of this class has been
      identified. The arrangement of the helices was studied by their propensity to
      form interhelix disulfide linkages and analysis of the stability and shape of
      disulfide-linked dimers. Disulfides formed preferentially between cysteine
      residues in an a position of one helix and either of the adjacent h positions of
      the partner. Such heterodimers were far more stable to thermal denaturation than
      homodimers and, on the basis of gel-filtration chromatography studies, were
      similar in shape to both non-covalent dimers and dimers linked through flexible
      Gly(1-3)Cys C-terminal extensions. The results indicate a right-handed coiled
      coil structure with intrinsic asymmetry, the two helices being offset rather than
      in register. A function for the right-handed coiled coil in rotational catalysis
      is proposed.

PMID- 17028023
TI  - Structure of Halothiobacillus neapolitanus carboxysomes by cryo-electron
      tomography.
AB  - Carboxysomes are polyhedral bodies consisting of a proteinaceous shell filled
      with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO). They are found in
      the cytoplasm of all cyanobacteria and some chemoautotrophic bacteria. Previous
      studies of Halothiobacillus neapolitanus and Nitrobacter agilis carboxysomes
      suggest that the structures are either icosahedral or dodecahedral. To determine
      the protein shell structure more definitively, purified H. neapolitanus
      carboxysomes were re-examined by cryo-electron tomography and scanning
      transmission electron microscopy (STEM). Due to the limited tilt angles in the
      electron microscope, the tomographic reconstructions are distorted. Corrections
      were made in the 3D orientation searching and averaging of the computationally
      extracted carboxysomes to minimize the missing data effects. It was found that H.
      neapolitanus carboxysomes vary widely in size and mass as shown by cryo-electron
      tomography and STEM mass measurements, respectively. We have aligned and averaged
      carboxysomes in several size classes from the 3D tomographic reconstruction by
      methods that are not model-biased. The averages reveal icosahedral symmetry of
      the shell, but not of the density inside it, for all the size classes.

PMID- 17028024
TI  - GFP technology for the study of biocontrol agents in tritrophic interactions: a
      case study with Pseudozyma flocculosa.
AB  - GFP technology was applied to the biocontrol agent (BCA) Pseudozyma flocculosa to
      study its development and interactions at the tritrophic level plant-powdery
      mildew-BCA. Transformation experiments with GFP led to the production of a
      strongly fluorescent strain, Act-4, that displayed biocontrol traits typical of
      P. flocculosa WT. Following inundative applications, growth of P. flocculosa Act
      4 was closely and almost exclusively associated with the colonies of the pathogen
      regardless of the powdery mildew species or the host plant tested. Development of
      P. flocculosa Act-4 on control leaves alone was extremely limited 24 h after its
      application and was typical of the epiphytic growth characterizing this type of
      yeast-like fungus. Based on the strong correlation between the colonization
      pattern of the different powdery mildew species tested and the presence of P.
      flocculosa Act-4, as determined by its fluorescence, it seems that growth of the
      BCA is dependant on the presence of powdery mildews. These results demonstrate
      that the GFP technology can be used to study plant-pathogen-BCA interactions and
      fulfill a wide array of purposes ranging from fundamental observations of the
      biocontrol behavior of a BCA to very applied ones serving some of the
      requirements for the registration of BCA's such as defining their environmental
      fate.

PMID- 17028025
TI  - Basal cortisol and DHEA levels in women with borderline personality disorder.
AB  - Previous research suggests that in borderline personality disorder (BPD) normal
      stress regulation, with a main role for cortisol, is disturbed. However, most
      studies were confounded by their lack of attention to co-morbidity. Relevant
      patient characteristics such as depression, childhood abuse, posttraumatic stress
      disorder (PTSD) and copying styles were not systematically examined. Moreover,
      none of the studies incorporated dehydroepiandrosterone (DHEA), a hormone that
      can antagonize the effects of cortisol. Hence, the present pilot study
      investigates the basic levels of cortisol and DHEA and the ratio (CDR) between
      the two hormones in BPD patients. Twenty-two women with BPD and 22 healthy female
      controls provided two diurnal (8 a.m./8 p.m.) salivary samples. Overall cortisol
      levels were not significantly increased in the patient group as a whole but only
      in those patients diagnosed with co-morbid PTSD and a history of childhood abuse.
      The patients' cortisol secretions decreased relatively less steep during the day
      than it did in the controls. Surprisingly, morning DHEA levels were significantly
      higher in the patients than in the controls. Moreover, the CDR showed a
      significantly larger and less favourable increase in the BPD group during the
      day. In the patients lower levels of DHEA in the evening proved significantly
      related to a stronger tendency to avoid active problem solving and a lowered
      inclination to seek social support. The current findings underline the relevance
      of cortisol and DHEA assessments and the need for further scrutiny of their
      interplay to foster our understanding of the biological basis of stress
      regulation in BPD.

PMID- 17028026
TI  - Comparing safety climate factors as predictors of work-related driving behavior.
AB  - INTRODUCTION: Research suggests safety climate (SC) is a strong predictor of
      safety-related outcomes in organizations. This study explores the relationship
      between six SC dimensions and four aspects of work-related driving. METHOD: The
      SC factors measured were "communication and procedures," "work pressures,"
      "relationships," "safety rules," "driver training," and "management commitment."
      The aspects of self-reported occupational driving measured were traffic
      violations, driver error, driving while distracted, and pre-trip vehicle
      maintenance. RESULTS: Hierarchical regression analyses revealed that the SC
      factors accounted for significant amounts of variance in all four aspects of work
      related driving, over and above the control factors of age, sex, and work-related
      driving exposure. However, further investigation indicated certain SC factors
      (particularly safety rules, communication, and management commitment) were more
      strongly related to specific aspects of work-related driving behavior than
      others. Together, the SC factors were better able to predict self-reported
      distraction from the road than the other aspects of driving behavior measured.
      Implications for occupational safety, particularly for the management of work
      related drivers are discussed.

PMID- 17028027
TI  - Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin
      variant tetramers in serum against dissociation required for amyloidogenesis.
AB  - Transthyretin (TTR) tetramer dissociation, misfolding and misassembly are
      required for the process of amyloid fibril formation associated with familial
      amyloid polyneuropathy (FAP). Preferential stabilization of the native TTR
      tetramer over the dissociative transition state by small molecule binding raises
      the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Two
      NSAIDs, diflunisal and flufenamic acid, and trivalent chromium have this ability.
      Here, we investigated the feasibility of using these molecules for the treatment
      of FAP utilizing serum samples from 37 FAP patients with 10 different mutations.
      We demonstrated that the TTR heterotetramer structures in FAP patients serum are
      significantly less stable than that in normal subjects, indicating the
      instability of the variant TTR structure is a fundamental cause of TTR
      amyloidosis. We also demonstrated that therapeutic serum concentrations of
      diflunisal (100-200 microM) stabilized serum variant TTR tetramer better than
      those of flufenamic acid (35-70 microM). Trivalent chromium at levels obtained by
      oral supplementation did not stabilize TTR in a statistically significant
      fashion. Importantly, diflunisal increased serum TTR stability in FAP patients
      beyond the level of normal controls.

PMID- 17028029
TI  - Voltage-gated potassium channel antibodies associated limbic encephalitis in a
      patient with invasive thymoma.
AB  - Recently, limbic encephalitis (LE) associated with Voltage-gated potassium
      channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most
      previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and
      reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman
      with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive
      thymoma. There was a close temporal relationship between the clinical course and
      the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab
      associated LE cases, our cases showed the more extensive high intensity lesions
      on MRI and the absence of seizure and hyponatremia.

PMID- 17028028
TI  - Chronic high-dose haloperidol has qualitatively similar effects to risperidone
      and clozapine on immediate-early gene and tyrosine hydroxylase expression in the
      rat locus coeruleus but not medial prefrontal cortex.
AB  - Acute administration of clozapine has been reported to activate the locus
      coeruleus (LC) and beta-adrenoceptor-dependent Fos immunoreactivity in the medial
      prefrontal cortex (mPFC) in rodents. Haloperidol is reported to exhibit a similar
      acute effect on LC firing and beta-adrenoceptor dependent Fos immunoreactivity in
      the mPFC but only at high doses. We compared the effects of chronic 4-week
      treatment with risperidone (1mg/kg/day s.c.), clozapine (10mg/kg/day s.c.) or a
      high dose of haloperidol (4mg/kg/day s.c.) on immediate-early gene protein (c
      Fos, Egr-1 and Egr-2) and tyrosine hydroxylase (TH) expression. In the mPFC,
      haloperidol decreased, whereas clozapine increased, c-Fos immunoreactivity. Only
      haloperidol increased Egr-1 immunoreactivity. There was no significant effect on
      Egr-2 immunoreactivity. In the LC, both Egr-1 and Egr-2 expression was down
      regulated by all three antipsychotics. Clozapine and risperidone increased TH
      immunoreactivity in both mPFC and LC. Haloperidol caused a smaller increase in TH
      expression in the LC, but did not alter expression in the mPFC. In conclusion,
      despite qualitatively similar effects in the LC, chronic treatment with
      haloperidol had different effects to clozapine and risperidone in the mPFC. This
      may relate to the reported advantage of clozapine and risperidone over
      haloperidol against prefrontal cortical-dependent cognitive and negative
      symptoms.

PMID- 17028031
TI  - Yeast cell inactivation related to local heating induced by low-intensity
      electric fields with long-duration pulses.
AB  - The effects of electric field (EF) treatments on Saccharomyces cerevisiae
      viability were investigated using a PG200 electroporator (Hoefer Scientific
      Instrument, San Fransisco, CA, USA) with specific attention to induced thermal
      effects on cell death. Lethal electric fields (1.5 kV cm(-1) for 5 s) were shown
      to cause heat variations in the cell suspension medium (water+glycerol), while
      corresponding classical thermal treatments at equivalent temperatures had no
      effect on the cells viability. Variations of the electrical conductivity of the
      intra- and extracellular matrix caused by ions and solutes transfer across the
      membrane were shown to be involved in the observed heating. The results permitted
      to build a theoretical model for the temperature variations induced by electric
      fields. Using this model and the electrical conductivity of the different media,
      a plausible explanation of the cell death induced by low-intensity electric
      fields with long-duration pulses has been proposed. Indeed, cell mortality could
      in part be caused by direct and indirect effects of electric fields. Direct
      effects are related to well known electromechanical phenomena, whereas indirect
      effects are related to secondary thermal stress caused by plasma membrane
      thermoporation. This thermoporation was attributed to electrical conductivity
      variations and the corresponding intracellular heating.

PMID- 17028030
TI  - Occurrence of nervous system involvement in SIRS.
AB  - Systemic inflammatory response syndrome (SIRS) is a medical condition in which
      the all-organ microcirculation is affected including nervous system. We describe
      neurological findings in 64 patients with SIRS at Hospital das Clinicas of Sao
      Paulo University School of Medicine; 45.3% were male and 54.7% female; their age
      ranged from 16 to 95 years old. SIRS was caused by infection in 68.8% of
      patients, trauma in 10.9%, burns in 7.8%, and elective surgery in 4.7%. The
      central nervous system involvement occurred in 56.3% of patients and was
      characterized as encephalopathy in 75%, seizures in 13.9%, non-epileptic
      myoclonus in 2.8%, and ischemic stroke in 8.3%. The magnetic resonance imaging,
      cerebrospinal fluid and electroencephalographic changes were unremarkable in
      encephalopathic patients. Neuromuscular disorders were diagnosed in 43.7%.
      Critical ill polyneuropathy was characterized in 57.1%, critical ill myopathy in
      32.1%, demyelinating neuropathy in 7.2%, and pure motor neuropathy in 3.6%. Nerve
      and muscle pathological studies dismissed inflammatory abnormalities. The
      identification of these conditions has important economic implications and may
      change the critically ill patients' prognosis.

PMID- 17028032
TI  - On the lag phase and initial decline of microbial growth curves.
AB  - The lag phase is generally thought to be a period during which the cells adjust
      to a new environment before the onset of exponential growth. Characterizing the
      lag phase in microbial growth curves has importance in food sciences,
      environmental sciences, bioremediation and in understanding basic cellular
      processes. The goal of this work is to extend the analysis of cell growth curves
      and to better estimate the duration of the lag phase. A non-autonomous model is
      presented that includes actively duplicating cells and two subclasses of non
      duplicating cells. The growth curves depend on the growth and death rate of these
      three subpopulations and on the initial proportion of each. A deterministic and a
      stochastic model are both developed and give the same results. A notable feature
      of the model is the decline of cells during the early stage of the growth curve,
      and the range of parameters when this decline occurs is identified. A limited
      growth model is also presented that accounts for the lag, exponential growth and
      stationary phase of microbial growth curves.

PMID- 17028033
TI  - Orientational control is an efficient control mechanism for phase switching in
      the E. coli fim system.
AB  - The fim system in E. coli controls the expression of type-1 fimbriae. These are
      hair-like structures that can be used to attach to host cells. Fimbriation is
      controlled by a mechanism called "orientational control." We present two families
      of models for orientational control to understand the details of how it works. We
      find that the main benefits of orientational control are that (i) it allows rapid
      adjustment of fimbriation levels in response to a change of environmental
      conditions while (ii) keeping the overall frequencies with which a cell switches
      between the fimbriate state and the afimbriate state low. The main reason for the
      efficiency of orientational control in regulation of fimbriation levels is that
      it keeps the system far from its steady state.

PMID- 17028034
TI  - Probing the role of microenvironment for microencapsulated Sacchromyces
      cerevisiae under osmotic stress.
AB  - Cell encapsulation opens a new avenue to the oral delivery of genetically
      engineered microorganism for therapeutic purpose. Osmotic stress is one of the
      universal chemical stress factors in the application of microencapsulation
      technology. In order to understand the effect and mechanism of the encapsulated
      microenvironment on protecting cells from hyper-osmotic stress, yeast cells of
      Saccharomyces cerevisiae Y800 were encapsulated in calcium alginate micro-gel
      beads (MB), alginate-chitosan-alginate (ACA) solid core microcapsules (SCM), and
      ACA liquid core microcapsules (LCM), respectively. The stress-induced
      intracellular components and enzyme activity including trehalose, glycerol and
      super oxide dismutase (SOD) were measured. Free cell culture was used as control.
      The survival of encapsulated cells and the cells released from MB, SCM and LCM
      after osmotic shock induced by NaCl solution (1, 2 and 3M) was evaluated. An
      analysis method was established to probe the effect of encapsulated
      microenvironment on the cell tolerance to osmotic stress. The results showed that
      LCM gave rise to the highest level of intracellular trehalose and glycerol, and
      SOD activity, as well as the highest survival rate of encapsulated cells or cells
      released from microcapsule. It was demonstrated that LCM was able to induce the
      highest stress response and stress tolerance of cells, which was adapted during
      culture, while SCM failed. The theoretical analysis revealed that it was the
      liquid alginate matrix in microcapsule that played a central role in
      domesticating the cells to adapt to hyper-osmotic stress. This finding provides a
      very useful guideline to cell encapsulation.

PMID- 17028035
TI  - Tumor necrosis factor alpha alters Na+-K+ ATPase activity in rat cardiac
      myocytes: involvement of NF-kappaB, AP-1 and PGE2.
AB  - There has been increasing evidence that tumor necrosis factor alpha (TNF-alpha)
      is synthesized by cardiomyoctes and contributes to their impaired function and to
      cardiac failure. Because the Na(+)-K(+) ATPase is a key player in the contraction
      of cardiomyocytes, this work was undertaken to study the effect of TNF-alpha on
      the Na(+)-K(+) ATPase in rat heart. Sprague Dawley rats (Rattus norvegicus) were
      injected with TNF-alpha (270 ng/100 g body weight) and 4 h later the ventricles
      were isolated, homogenized and assayed for their Na(+)-K(+) ATPase activity. The
      effect of TNF-alpha on the pump was studied also in isolated myocytes treated in
      suspension. The involvement of PGE2 was investigated by pre-treating animals or
      cells with indomethacin, an inhibitor of COX enzymes. The involvement of NF
      kappaB and AP-1 was studied using their respective inhibitors PDTC and curcumin.
      A time response study showed an increase in the activity of the Na(+)-K(+) ATPase
      in the left and right ventricles of animals treated with the cytokine, with no
      change in its protein expression. This effect disappeared in the presence of
      indomethacin suggesting an involvement of PGE(2) in the action of TNF-alpha. Rats
      and cells treated directly with PGE(2) showed a dose-dependent response. A
      decrease in the activity of the Na(+)-K(+) ATPase was observed at a low dose and
      an increase at a high dose in both ventricles. Since PGE(2) is suspected to be
      the active mediator in TNF-alpha signaling, inhibiting its synthesis by
      inhibiting some suspected transcription factors was attempted. PDTC abrogated
      fully, and curcumin partially the effect of the cytokine. It was concluded that
      TNF-alpha activates NF-kappaB and AP-1 and induces PGE(2) release which alters
      dose-dependently the activity of the pump by activating different EP receptors
      with different affinities for PGE(2).

PMID- 17028036
TI  - Cyclopamine treatment of human embryonic stem cells followed by culture in human
      astrocyte medium promotes differentiation into nestin- and GFAP-expressing
      astrocytic lineage.
AB  - Human embryonic stem cells (hESCs) are able to differentiate into various cell
      types, including neuronal cells and glial cells. However, little information is
      available regarding astrocyte differentiation. This report describes the
      differentiation of hESCs into nestin- and GFAP-expressing astrocytes following
      treatment with cyclopamine, which is an inhibitor of Hedgehog (Hh) signaling, and
      culturing in human astrocyte medium (HAM). In hESCs, cyclopamine treatment
      suppressed the expression of Hh signaling molecules, the Hh signaling target
      gene, and ESC-specific markers. Clyclopamine also induced the differentiation of
      the cells at the edges of the hESC colonies, and these cells stained positively
      for the early neural marker nestin. Subsequent culturing in HAM promoted the
      expression of the astrocyte-specific marker GFAP, and these cells were also
      nestin-positive. These findings indicate that treatment with cyclopamine followed
      by culturing in HAM leads to the differentiation of hESCs into nestin- and GFAP
      expressing astrocytic lineage.

PMID- 17028037
TI  - Assessing the impact of nutrient enrichment in estuaries: susceptibility to
      eutrophication.
AB  - The main aim of this study was to develop a generic tool for assessing risks and
      impacts of nutrient enrichment in estuaries. A simple model was developed to
      predict the magnitude of primary production by phytoplankton in different
      estuaries from nutrient input (total available nitrogen and/or phosphorus) and to
      determine likely trophic status. In the model, primary production is strongly
      influenced by water residence times and relative light regimes. The model
      indicates that estuaries with low and moderate light levels are the least likely
      to show a biological response to nutrient inputs. Estuaries with a good light
      regime are likely to be sensitive to nutrient enrichment, and to show similar
      responses, mediated only by site-specific geomorphological features. Nixon's
      scale was used to describe the relative trophic status of estuaries, and to set
      nutrient and chlorophyll thresholds for assessing trophic status. Estuaries
      identified as being eutrophic may not show any signs of eutrophication.
      Additional attributes need to be considered to assess negative impacts. Here,
      likely detriment to the oxygen regime was considered, but is most applicable to
      areas of restricted exchange. Factors which limit phytoplankton growth under high
      nutrient conditions (water residence times and/or light availability) may favour
      the growth of other primary producers, such as macrophytes, which may have a
      negative impact on other biological communities. The assessment tool was
      developed for estuaries in England and Wales, based on a simple 3-category
      typology determined by geomorphology and relative light levels. Nixon's scale
      needs to be validated for estuaries in England and Wales, once more data are
      available on light levels and primary production.

PMID- 17028038
TI  - Reversibly stable thiopolyplexes for intracellular delivery of genes.
AB  - Novel polyaspartamide non-viral carriers for gene therapy were synthesized by
      introducing, on the same polymer backbone, positively charged groups, for
      electrostatic interactions with DNA, and thiol groups for the formation of
      disulfide bridges between polymer chains. The introduction of thiols was aimed to
      have a vector with low redox potential sensitivity: disulfide crosslinking in
      fact, being stable in extracellular environment, allowed either to have stable
      complexes in plasma, that can protect DNA from metabolism, or to be reduced
      inside the cell, where the excess of glutathion in reduced form maintains a low
      redox potential. The consequent destabilization of the complex after disulfide
      cleavage can release DNA selectively inside the cells. Alpha,beta-poly(N-2
      hydroxyethyl)-D,L-aspartamide (PHEA) was used as starting polymer being a highly
      water-soluble synthetic polymer, already proposed with success as therapeutic
      carrier by our group. In this study, PHEA was firstly functionalised with
      ethylendiamine, obtaining a well defined copolymer with pendant primary amine
      groups (PHEA-EDA), to which N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP)
      and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) were linked in two
      subsequent steps, allowing the introduction of thiol and cationic groups
      respectively. Finally DTT treatment lead to the final PHEA-EDA-SH-CPTA
      thiopolycation, named PESC. The present work describes the synthesis and
      characterization of the thiopolycation PESC. 1H NMR spectroscopy detected the
      derivatization molar degrees in SPDP and CPTA; the formation of DNA complexes
      (thiopolyplexes), their stability in the presence of polyanions and the ability
      to release DNA under reductive conditions were studied by agarose gel
      electrophoresis. DNase II degradation study was carried out to detect the ability
      of thiopolyplex to stabilize DNA towards enzymatic metabolism. Thiopolyplexes
      were then characterized by Dynamic Light Scattering (DLS) and Zeta Potential
      analysis. Finally, in vitro toxicity profile (MTT) and gene transfer efficiency
      (Luciferase assay) were carried out to evaluate thiopolyplex biocompatibility,
      safety and efficacy to be used as gene delivery system.

PMID- 17028039
TI  - Protective effects of transcription factor HESR1 on retinal vasculature.
AB  - HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch
      signaling pathway in vertebrate and Drosophila embryos, and is related to the
      HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial
      cells and could be an effector of Notch signaling in these cells. HESR1 is
      necessary for the induction of a tubular network and for continued maintenance of
      mature and quiescent blood vessels. To examine the role of HESR1 in retinal
      neovascularization, we transfected retinal vascular endothelial cells (HRCECs)
      with the HESR1 gene and studied its effects on the expression of angiogenic
      factors, on the proliferation and migration of endothelial cells, and on the
      formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated
      VEGFR-2 expression, upregulated occludin expression, inhibited the migration and
      proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a
      key role in the finely tuned network of molecules involved in the regulation of
      retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects
      of VEGF, shift endothelial cells from a proliferative state to a quiescent state,
      and restore normal vessel structures. Expression of the HESR1 gene in retinal
      vascular endothelial cells may protect retinal blood vessels and may be useful in
      the treatment of diseases involving damage to the retinal vasculature, including
      diabetic retinopathy, age-related macular degeneration, and retinal vein
      occlusion.

PMID- 17028040
TI  - Effects of big endothelin-1 in comparison with endothelin-1 on the microvascular
      blood flow velocity and diameter of rat mesentery in vivo.
AB  - Synthetic big endothelin-1 (ET-1), a 39-residue precursor of ET-1, has been
      reported to elicit potent contractile action on helical strip specimens obtained
      from the porcine coronary artery, but its molar potency was found to be 140-fold
      lower than that of ET-1 [Saito, Y., Nakao, K., Mukoyama, M., Imura, H., 1990.
      Increased plasma endothelin level in patients with essential hypertension. N.
      Engl. J. Med. 322, 205]. It has been hypothesized that the increased rate of
      production and/or release of ET-1 from the vascular endothelium may contribute to
      the pathogenesis of hypertension. However, the effects of big ET-1 in comparison
      with ET-1 on the macrocirculation and microcirculation of the rat mesentery have
      not been well documented. Thus, our main purpose for this study was to examine
      the effects of both big ET-1 and ET-1 to clarify the role of phosphoramidon in
      inhibiting the conversion of big ET-1 to ET-1, by investigating the systemic
      blood pressure, microvascular blood flow velocity, and diameters of arterioles
      and venules of the rat mesentery. For this purpose, two groups of experiments
      were performed. In these experiments, the mesentery was arranged for in situ
      intravital microscopic observation under transillumination. In the first group of
      experiments, intravenous cumulative injections of big ET-1 or ET-1 were infused
      through a catheter inserted into the right jugular vein. Infusion of big ET-1 (1
      8 nmol/kg) elicited a long-lasting significant pressor effect. Infusion of big ET
      1 (1-2 nmol/kg) elicited a significant dose-dependent increase in the
      microvascular blood flow velocity both in arterioles (20-30 microm) and venules
      (30-40 microm). Microvascular diameters exhibited a slight but significant
      vasodilator effect. However, the infusion of big ET-1 (4-8 nmol/kg) elicited a
      dose-dependent significant decrease in the blood flow velocities, and diameters
      returned to control measurements. The administration of ET-1 (0.25-2 nmol/kg)
      induced a dose-dependent significant decrease in the blood flow velocity of
      arterioles and venules, and their diameters exhibited a vasoconstrictive effect
      more prominent in arterioles than in venules. In the second group of experiments,
      cumulative injections of phosphoramidon (30 mg/kg/10 min) were administered 10
      min prior to the infusion of big ET-1. Phosphoramidon significantly suppressed
      the long-lasting significant pressor effect and significantly inhibited the dose
      dependent increase and dose-dependent decrease in the microvascular blood flow
      velocity produced by big ET-1 in the rat mesenteric microcirculation. This study
      observed differences in the effects big ET-1 and ET-1 have on the rat mesenteric
      microcirculation and proposes a possible mechanism explaining these differences.
      Moreover, phosphoramidon markedly inhibited the conversion of big ET-1 to ET-1 in
      the rat mesenteric microcirculation, which may suggest an inhibition of the
      enzyme which converts big ET-1 to ET-1.

PMID- 17028041
TI  - Ionizing radiation decreases capillary-like structure formation by endothelial
      cells in vitro.
AB  - For successful tissue engineering in surgical radiotherapy patients, irradiated
      endothelial cells (EC) must form new blood vessels to nourish and build
      connections with the engineered segment. Therefore, it is critical to understand
      neovasculogenesis by irradiated EC. The objective of this study was to determine
      the effects of ionizing radiation on endothelial cell proliferation and capillary
      like structures (CLS) formation. Human Umbilical Vein Endothelial Cells (HUVEC)
      were irradiated with single or fractionated doses of radiation. Proliferation was
      determined by counting cells. CLS morphology was analyzed from photomicrographs.
      A single dose of 8 Gy radiation was highly lethal to HUVEC compared to lower
      dosage. A single dose had more of an inhibitory effect on cell proliferation
      compared to the same dose delivered in a fractionated manner. CLS formation began
      after cells reached confluency. To form a CLS, a single cell expanded, and a
      number of cells rearranged around its periphery in an oval fashion (mimicking a
      vessel wall). The central cell later disintegrated leaving a void, mimicking the
      lumen. Irradiated EC can form CLS, although they are fewer and smaller compared
      to those by sham cells. By disrupting the peripheral cells, >or=4 Gy doses
      significantly reduced the number of CLS. The disruptive affect was seen more with
      large CLS compared to small CLS. At different doses, the shapes of CLS were not
      significantly different.

PMID- 17028042
TI  - Price differences between Japan and the US for medical materials and how to
      reduce them.
AB  - INTRODUCTION: Previous reports (1996, 1997) have revealed that the market prices
      of medical materials in Japan were two to four times higher than those in the US.
      The Japanese government introduced the foreign price adjustment rule (FPA) in
      2002 to reduce reimbursement prices in Japan. We aimed to investigate the current
      price differences between Japan and the US in the first half of 2005 and to
      evaluate the effectiveness of the FPA. METHODS: The investigation was performed
      at two joint purchasing organizations (JPO) and a hospital group in the US, and
      at a university hospital in Japan. Forty-one items in 14 categories were selected
      in advance. RESULTS: The price ratio (Japanese price/US price) was largest at 4.5
      6.8 for percutaneous transluminal coronary angioplasty (PTCA) balloon catheters
      and 1.4-6.0 for vascular grafts. The price ratio was smallest at 1.2-2.4 for
      automatic sutures, 1.4-1.6 for Swan-Ganz catheters, and 1.5-2.3 for mechanical
      valves. DISCUSSION: The price differences between Japan and the United States
      were found to have rather widened with the exception of the pacemaker, because
      their market prices decreased more markedly in the United States. The
      investigation suggests several problems with the FPA: (1) the determination
      process of reimbursement prices is inappropriate, which has made the Japanese
      market less competitive, (2) the FPA needs too much time for the resolution of
      price differences, and (3) price data collected according to the FPA lacks
      strictness. CONCLUSIONS: The high prices of medical material in Japan need to be
      adjusted down with more appropriate measures such as the full cost or cost
      inclusion methods.

PMID- 17028043
TI  - Patient (customer) expectations in hospitals.
AB  - The expectations of patient are one of the determining factors of healthcare
      service. The purpose of this study is to measure the Patients' Expectations,
      based on Patient's Rights. This study was done with Likert-Survey in Trabzon
      population. The analyses showed that the level of the expectations of the patient
      was high on the factor of receiving information and at an acceptable level on the
      other factors. Statistical meaningfulness was determined between age, sex,
      education, health insurance, and the income of the family and the expectations of
      the patients (p<0.05). According to this study, the current legal regulations
      have higher standards than the expectations of the patients. The reason that the
      satisfaction of the patients high level is interpreted due to the fact that the
      level of the expectation is low. It is suggested that the educational and public
      awareness studies on the patients' rights must be done in order to increase the
      expectations of the patients.

PMID- 17028044
TI  - Genetic variance contributes to ingestive processes: a survey of eleven inbred
      mouse strains for fat (Intralipid) intake.
AB  - Genetic variation across inbred and outbred mouse strains have been observed for
      intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our
      laboratory recently reported marked strain differences in the amounts and/or
      percentages of kilocalories of sucrose consumed among 11 inbred and one outbred
      mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%)
      in two-bottle 24-h preference tests. To assess whether differences in fat intake
      were similarly associated with genetic variation, the present study examined
      intake of chow, water and an emulsified fat source (Intralipid) across nine
      different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse
      strains using two-bottle 24-h preference tests, which controlled for Intralipid
      concentration presentation effects, Intralipid and water bottle positions, and
      measurement of kilocalorie intake consumed as Intralipid or chow. Strains
      displayed differential increases in Intralipid intake relative to corresponding
      water with significant effects observed at the seven (BALB/cJ: 0.001% threshold
      sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity),
      three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J,
      C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing
      the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed
      significantly more at the three highest concentrations to a greater degree than
      BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn
      consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong
      (h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted
      Intralipid intake at those concentrations (0.001-1%) that displayed the largest
      strain-specific effects in sensitivity to Intralipid. The identification of
      strains with diverging abilities to regulate kilocalorie intake when presented
      with high Intralipid concentrations may lead to the successful mapping of genes
      related to hedonics and obesity.

PMID- 17028045
TI  - Differential effects of hypocretins on noise-alone versus potentiated startle
      responses.
AB  - Hypocretins are recently discovered neuropeptides, synthesized exclusively in the
      hypothalamus with excitatory efferents to noradrenergic, serotonergic, and
      GABAergic (gamma-aminobutyric acid) neurons. Hypocretins also increase
      corticotropin releasing hormone (CRH) secretion. These actions suggest a possible
      role for hypocretins in the neurobiology of anxiety, fear, or startle mechanisms.
      We examined the effects of intracerebroventricular (ICV) administration of
      hypocretin-A and hypocretin-B on behavior in the Startle Potentiated Startle
      (SPS) paradigm, a repeated measures, non-shock animal model for studying the
      classically conditioned enhancement of acoustic startle in the rat. SPS has been
      used to study effects of anxiolytic treatments. Male Sprague-Dawley rats were
      tested using the SPS paradigm for 3 days (M-W-F). Following training, rats were
      anesthetized and 26 gauge stainless cannulae were permanently implanted into the
      lateral ventricle for intracerebroventricular (ICV) infusions. Following 6-9 days
      of recovery period, the M-W-F SPS testing was resumed. ICV infusion of both
      Hypocretin-A (1 and 3 nM) and Hypocretin-B (3 and 10 nM) produced significant
      reduction in Noise Alone Startle amplitude compared to pre-infusion baseline,
      whereas infusion with vehicle did not affect Noise Alone Startle. The effect of
      Hypocretin-B was brief (first 10 min post-infusion), whereas the effect of
      Hypocretin-A persisted across much of the 50 min post-infusion period. Neither
      Hypocretin-A nor Hypocretin-B significantly altered the magnitude of the SPS
      response. Contrary to our expectations, hypocretins seems to possess anxiolytic
      rather than pro-anxiogenic properties, as indicated by decrease in Noise Alone
      Startle.

PMID- 17028046
TI  - The effect of monosodium glutamate on parotid salivary flow in comparison to the
      response to representatives of the other four basic tastes.
AB  - Parotid salivary flow was recorded from eight fit and healthy subjects using
      modified Lashley cups connected to an instantaneous flow meter in response to
      gustatory stimuli. The gustatory stimuli were monosodium glutamate (MSG), sodium
      chloride, sucrose, magnesium sulphate and citric acid. Stimuli were applied for
      30 s, and repeated after the flows had returned to baseline following the rinse.
      Subjects were a significant source of variation for salivary response to each
      different test stimuli (p<0.001). The normalised salivary flow showed a strong
      correlation to concentration for all test stimuli (p<0.0001). The parotid
      salivary flow to MSG (umami) showed a dose-dependant response in which both Na(+)
      and glutamate ions contributed. The overall order of relative salivary flow
      responses from highest to lowest flows was citric acid (sour)>MSG (umami)>NaCl
      (salt)>sucrose (sweet)>=magnesium sulphate (bitter). The relative responses of
      the peak salivary flows showed the same ordered relation. The peak salivary flow
      provided a greater contribution to the response to citric acid, NaCl and MSG
      compared to the response to sucrose and magnesium sulphate.

PMID- 17028047
TI  - Control of Schistosoma mekongi in Cambodia: results of eight years of control
      activities in the two endemic provinces.
AB  - In Cambodia, schistosomiasis is transmitted in the provinces of Kratie and Stung
      Treng where approximately 80000 individuals are estimated to be at risk of
      infection. The baseline prevalence of infection was estimated to be between 73%
      and 88%, and cases of severe morbidity (hepatosplenomegaly, puberty retardation)
      and mortality were very common. In 1994, the Ministry of Health of Cambodia
      started schistosomiasis control applying universal chemotherapy with praziquantel
      (40mg/kg). The coverage of the programme was between 62% and 86% for 8 years.
      This simple control measure resulted in the control of the disease: no cases were
      reported in 2004 and only three cases were reported in 2005. In addition, there
      are no longer reports of cases of severe morbidity due to schistosomiasis. Since
      the beginning of the control programme, a single dose of mebendazole (500mg) has
      been combined with praziquantel during the mass chemotherapy; as a result the
      prevalence of Ascaris lumbricoides and hookworms dropped from 74.5% to 10% and
      from 86% to 40% respectively. The experience in Cambodia demonstrates that, with
      political commitment, control of parasitic diseases is achievable even in a
      situation of minimal resources. The programme represents a successful model for
      other developing countries.

PMID- 17028048
TI  - Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to
      chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia.
AB  - To determine the level of antimalarial drug resistance in southern Papua,
      Indonesia, we assessed the therapeutic efficacy of chloroquine plus sulfadoxine
      pyrimethamine (CQ+SP) for Plasmodium falciparum infections as well as CQ
      monotherapy for P. vivax infections. Patients with P. falciparum failing therapy
      were re-treated with unsupervised quinine+/-doxycycline therapy and those with P.
      vivax with either unsupervised quinine+/-doxycycline or amodiaquine. In total,
      143 patients were enrolled in the study (103 treated with CQ+SP and 40 with CQ).
      Early treatment failures occurred in four patients (4%) with P. falciparum and
      six patients (15%) with P. vivax. The failure rate by Day 28 for P. vivax was 65%
      (95% CI 49-81). After PCR correction for re-infections, the Day 42 recrudescence
      rate for P. falciparum infections was 48% (95% CI 31-65). Re-treatment with
      unsupervised quinine+/-doxycycline resulted in further recurrence of malaria in
      48% (95% CI 31-65) of P. falciparum infections and 70% (95% CI 37-100) of P.
      vivax infections. Eleven patients with recurrent P. vivax were re-treated with
      amodiaquine; there were no early or late treatment failures. In southern Papua, a
      high prevalence of drug resistance of P. falciparum and P. vivax exists both to
      first- and second-line therapies. Preliminary data indicate that amodiaquine
      retains superior efficacy compared with CQ for CQ-resistant P. vivax.

PMID- 17028049
TI  - Type 2 11beta-hydroxysteroid dehydrogenase activity in human ovarian cancer.
AB  - In the ovary cortisol-cortisone inter-conversion is catalyzed by the enzyme
      11beta-hydroxysteroid dehydrogenase (11beta-HSD). Its role in carcinomas of human
      ovary is unknown. The majority of ovarian cancers are derived from ovarian
      surface epithelium and the inflammation caused by successive ovulation seems to a
      play a role in the development of cancer. Cortisol is known to act as anti
      inflammatory agent and its metabolism by type 1 and type 11beta-HSD may control
      the inflammatory action by cortisol in ovary. We undertook this study to
      investigate type 2 11beta-HSD activity which functions exclusively oxidative
      direction, in normal ovarian tissue compared to ovarian epithelial cancer.
      Ovarian tissue was obtained from patients undergoing hysterectomy for both benign
      and malignant disease. Tissue was placed immediately on dry ice and subsequently
      transferred to a freezer where they were maintained at -70 degrees C. NAD
      dependent 11beta-HSD activity was then determined in this tissue. T-test was
      performed to determine statistical significance. Mean type 2 enzyme activity was
      0.87 +/- 1.65 pmol/min g tissue in normal ovarian tissue versus a mean enzyme
      activity of 2.96 +/- 1.37 pmol/mim g tissue in from cancer specimens. This
      difference was statistically significant with a p-value of 0.03. Type 2 1beta-HSD
      activity in ovarian cancer specimens was significantly higher than enzyme
      activity measured in normal post-menopausal ovarian tissue. Decreased cortisol
      levels due type 2 1beta-HSD activity may play a role neoplastic transformation as
      well as tumor proliferation in ovarian cancer by eliminating anti-inflammatory
      action of cortisol.

PMID- 17028050
TI  - Mean curvature versus normality: a comparison of two approximations of Fisher's
      geometrical model.
AB  - Fisher's geometrical model amounts to a description of mutation and selection for
      individuals characterised by a number of quantitative traits. In the present work
      the fitness landscape is not assumed to be spherically symmetric, hence different
      points, i.e. phenotypes, on a surface of constant fitness generally have
      different curvatures. We investigate two different approximations of Fisher's
      geometrical model that have appeared in the literature. One approximation uses
      the average curvature of the fitness surface at the parental phenotype. The other
      approach is based on a normal approximation of a distribution associated with new
      mutations. Analytical results and simulations are used to compare the accuracy of
      the two approximations.

PMID- 17028051
TI  - Surnames in Western Europe: a comparison of the subcontinental populations
      through isonymy.
AB  - We studied the isonymic structure of Western Europe using the distributions of
      26.2 million surnames in 8 countries, 125 regions and 2094 towns of the
      Subcontinent. We found that, for the whole of Western Europe, Nei's distance was
      correlated with geographic distance (r=0.610+/-0.009). It was observed that at
      long geographic distances the isonymyc distance stays below linearity and tends
      to become asymptotic, and this was attributed to long distance migration. A
      dendrogram of the125 regions was built and the clusters identified by the
      dendrogram are almost exactly coincident with the nations of the Subcontinent.
      Random inbreeding calculated from isonymy, F(ST), was highest in Spanish regions,
      and lowest in France. The geographical distribution of alpha in 2094 towns, high
      in the Center and East of the Subcontinent and lower in Spain, is compatible with
      the settlement of subsequent waves of migrants moving from the West and from the
      South toward the centre of the Continent. The present surname structure of
      Western Europe is strictly linked to local languages.

PMID- 17028052
TI  - A proper schedule of weekly paclitaxel and gemcitabine combination is highly
      active and very well tolerated in NSCLC patients.
AB  - BACKGROUND: In a previous phase I dose-escalation study, we showed a weekly
      administration of paclitaxel (TAX) and gemcitabine (GEM) to be active and very
      well tolerated in non-small-cell lung cancer (NSCLC) patients, with the lack of
      interaction between drugs. The dose of GEM 1500 mg/m(2) and TAX 100 mg/m(2) was
      selected for phase II studies due to its predictable kinetic behaviour and less
      severe thrombocytopenia. PATIENTS AND METHODS: Fifty-four chemo-naive patients
      with advanced NSCLC (53 patients: stage IV) received TAX (100mg/m(2) i.v.
      infusion over 1h) followed by GEM 1500 mg/m(2) over 30 min) on days 1, 8, 15 and
      21 of a 28-day cycle. RESULTS: The objective response rate was 46% (95% CI 32
      61), median OS of 10.4 ms (95% CI 6.5-4.3), and a 1-year survival rate of 53%.
      Grades 3 and 4 haematological toxicity consisted of non-febrile neutropenia and
      thrombocytopenia in 13 and 4% of the cycles, respectively. Grade 3 non
      haematological toxicities were observed in three patients (asthenia, diarrhoea
      and neuropathy), and were always reversible. CONCLUSIONS: This weekly schedule of
      TAX and GEM is highly active in chemo-naive NSCLC patients and confirms the low
      toxicity profile already observed in a previous phase I study.

PMID- 17028053
TI  - Recognition of external object features in gas media using ultrasound
      transmission tomography.
AB  - The paper presents and analyzes a new way of recognizing external object features
      (shape, size, location) in gas media using ultrasound transmission tomography
      (UTT) with parallel-ray-projection scanning geometry. The concept of UTT in a gas
      medium is close to classical tomography, however because of the nature of the
      measurement environment, visualizing the internal structure of solid objects is
      difficult; whereas it is possible to image their external features: their shape,
      size and spatial location. The paper presents the results of examining the shape,
      size and location of different objects in the air in the form of tomographic
      images, obtained in parallel-ray-projection geometry, using a specially
      elaborated research setup for UTT. Applying parallel-ray-projection geometry
      enabled us to investigate the influence of scanning resolution on image quality.
      In order to test the operation of the elaborated algorithm of tomographic image
      reconstruction on the basis of correct measurement data, special software was
      written for simulating the binary matrix of the measurements for a set of a dozen
      or so solid objects of different shapes and a few simulations were performed.

PMID- 17028054
TI  - Merging theory and mechanism in studies of gynodioecy.
AB  - In gynodioecious species, females and hermaphrodites coexist and the genetics of
      sex determination is usually nuclear cytoplasmic. Maintaining nuclear-cytoplasmic
      gynodioecy requires polymorphism for the feminizing genes (contained in the
      mitochondria) and the genes that restore male fertility (contained in the
      nucleus). This complex polymorphism depends, in part, on there being negative
      pleiotropic effects (i.e. costs) of the nuclear restorer alleles. Here, we
      combine information from theoretical studies and studies on the molecular action
      of restorer alleles in crops to interpret the probable costs of such alleles, and
      suggest how various aspects of the theoretical models could be tested. In doing
      so, we highlight how crops can be used to address evolutionary questions about
      the maintenance of nuclear-cytoplasmic gynodioecy.

PMID- 17028055
TI  - The perils and prospects of using phytohaemagglutinin in evolutionary ecology.
AB  - Several techniques are available for quantifying the vertebrate immune response,
      information that is particularly useful for understanding the contribution of
      immunity to the evolution of life-history strategies. The most widely used is the
      phytohaemagglutinin (PHA) skin-swelling technique, which is usually regarded as
      an index of acquired immunity. However, our understanding of the effects of PHA
      in skin is poor, despite the fact that it has implications for what the test can
      tell us about immune activity. As we discuss here, a recent study by Martin and
      colleagues on the response to PHA at the cellular level in wild birds has
      highlighted the relative extent to which PHA-induced swelling, as most commonly
      applied, measures innate immunity versus acquired immunity.

PMID- 17028056
TI  - Mating and immunity in invertebrates.
AB  - Mating and immunity are intimately linked to fitness. In both vertebrates and
      invertebrates, recent investigations into mate choice for immunity, tradeoffs
      between reproduction and immunity, and the relationships between post-mating
      processes and immune function have revealed that mating and immunity are also
      intimately linked to each other. Here, we focus on invertebrates and critically
      examine the evidence that immunity is under sexual selection, both pre- and post
      mating, and explore other hypotheses linking mating and immunity. We find little
      evidence for a consensus regarding which theories best account for the
      accumulating empirical data. However, we suggest that progress can quickly be
      made by exploiting the intrinsic strengths of invertebrate model systems.

PMID- 17028057
TI  - Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein
      of Herpesvirus saimiri.
AB  - Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus
      saimiri, has been known to activate NF-kappaB signaling pathway, the detailed
      mechanism has not been reported yet. We herein report that STP-A11 activates non
      canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition,
      translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the
      expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein
      requires proteosome-mediated proteolysis because MG132 treatment clearly blocked
      p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants
      to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site
      not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11
      mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug
      mediated cell death, suggesting that p52 production induced by the expression of
      STP-A11 would contribute to cellular transformation, which results from a
      resistance to cell death.

PMID- 17028058
TI  - Efficacy of inactivated vaccines against H5N1 avian influenza infection in ducks.
AB  - The current Asian H5N1 highly pathogenic avian influenza virus has spread over
      much of Asia and into Europe and Africa. As well as affecting village and
      commercial chicken operations in many South East Asian countries, it differs from
      past H5 avian influenza viruses in that it causes morbidity and mortalities in
      other domesticated birds, such as ducks and turkeys and in wild water birds.
      Effective vaccines that can prevent infection, as well as disease, and be used in
      a variety of avian species are needed for field use. In this report, a bivalent
      H5N9+H7N1 oil emulsion vaccine is compared, in ducks, to a monovalent H5N3 oil
      emulsion vaccine that has been derived by reverse genetics with an H5 from
      A/chicken/Vietnam/C58/04. While both vaccines protected against morbidity, the
      monovalent vaccine provided effective protection, with no evidence of shedding of
      the challenge virus and no serological response to the H5N1 challenge virus.

PMID- 17028059
TI  - Marek's disease virus up-regulates major histocompatibility complex class II cell
      surface expression in infected cells.
AB  - Many herpesviruses modulate major histocompatibility complex (MHC) expression on
      the cell surface as an immune evasion mechanism. We report here that Marek's
      disease virus (MDV), a lymphotrophic avian alphaherpesvirus, up-regulates MHC
      class II cell surface expression in infected cells, contrary to all other
      herpesviruses examined to date. This MDV-induced class II up-regulation was
      detected both in vitro and in vivo. This effect was not solely an indirect effect
      of interferon, which is a highly potent natural inducer of MHC class II
      expression, since MHC class II up-regulation in cultured primary fibroblast cells
      was confined to the infected cells only. MHC class II up-regulation was also
      observed in infected cells of the bursa of Fabricius during the lytic phase of
      MDV infection in birds and upon reactivation of MDV from latency in an MDV
      transformed cell line. As MDV is a strictly cell-associated virus and requires
      activated T cells for its life cycle, this up-regulation of MHC class II in
      infected cells may contribute to virus spread within the infected host by
      increasing the chance of contact between productively infected cells and
      susceptible activated T cells.

PMID- 17028060
TI  - Injection of the sciatic nerve with TMEV: a new model for peripheral nerve
      demyelination.
AB  - Demyelination of the human peripheral nervous system (PNS) can be caused by
      diverse mechanisms including viral infection. Despite association of several
      viruses with the development of peripheral demyelination, animal models of the
      condition have been limited to disease that is either autoimmune or genetic in
      origin. We describe here a model of PNS demyelination based on direct injection
      of sciatic nerves of mice with the cardiovirus, Theiler's murine
      encephalomyelitis virus (TMEV). Sciatic nerves of FVB mice develop inflammatory
      cell infiltration following TMEV injection. Schwann cells and macrophages are
      infected with TMEV. Viral replication is observed initially in the sciatic nerves
      and subsequently the spinal cord. Sciatic nerves are demyelinated by day 5 post
      inoculation (p.i.). Injecting sciatic nerves of scid mice resulted in increased
      levels of virus recovered from the sciatic nerve and spinal cord relative to FVB
      mice. Demyelination also occurred in scid mice and by 12 days p.i., hindlimbs
      were paralyzed. This new model of virus-induced peripheral demyelination may be
      used to dissect processes involved in protection of the PNS from viral insult and
      to study the early phases of lesion development.

PMID- 17028061
TI  - Synthesis and characterization of novel biotinylated carboxyl-terminal
      parathyroid hormone peptides that specifically crosslink to the CPTH-receptor.
AB  - Parathyroid hormone (PTH) regulates calcium, phosphorous and skeletal homeostasis
      via interaction with the G protein-coupled PTH/PTHrP receptor, which is fully
      activated by the amino-terminal 34 amino-acid portion of the hormone. Recent
      evidence points to the existence of another class of receptors for PTH that
      recognize the carboxyl (C)-terminal region of intact PTH (1-84) (CPTHRs) and are
      highly expressed by osteocytes. Here we report the synthesis and characterization
      of two novel bifunctional CPTH ligands that include benzoylphenylalanine (Bpa)
      substitutions near their amino-termini and carboxyl-terminal biotin moieties, as
      well as a tyrosine(34) substitution to enable radioiodination. These peptides are
      shown to bind to CPTHRs with affinity similar to that of PTH (1-84) and to be
      specifically and covalently crosslinked to CPTHRs upon exposure to ultraviolet
      light. Crosslinking to osteocytes or osteoblastic cells generates complexes of 80
      and 220 kDa, of which the larger form represents an aggregate that can be
      resolved into the 80 kDa. The crosslinked products can be further purified using
      immunoaffinity and avidin-based affinity procedures. While the molecular
      structure of the CPTHR(s) remains undefined, these bifunctional ligands represent
      powerful new tools for use in isolating and characterizing CPTHR protein(s).

PMID- 17028062
TI  - Effects of design flow and treatment level on construction and operation costs of
      municipal wastewater treatment plants and their implications on policy making.
AB  - Construction costs of 55 municipal wastewater treatment plants in Israel
      (secondary, advanced secondary, and advanced treatment) were analysed in order to
      derive cost functions expressing the effects of design flow and treatment level
      on construction costs. Three equations were derived (statistically significant,
      p<0.01), one for each treatment level. These indicate that economy of scale may
      become weaker as treatment level rises. Analysis of the distribution of
      construction costs revealed negative correlation (p<0.05) between the
      proportional cost of civil engineering and design flow, positive correlation
      (p<0.05) between the proportional cost of elecromechanical equipment and design
      flow, and no correlation between the proportional cost of electricity and control
      and design flow. Operation costs were found to be 20-70% more sensitive than
      construction costs to treatment level. The share of operation costs as part of
      the total annual costs was found to increase both with design flow and treatment
      level, whereas the share of construction costs concurrently decreased. The
      implication of the findings on policy, and consequently on treatment plants
      performance is discussed in the last part of the paper.

PMID- 17028063
TI  - Degradation of endocrine disrupting bisphenol A by 254 nm irradiation in
      different water matrices and effect on yeast cells.
AB  - The photodegradation of bisphenol A (BPA) in pure water, surface water and
      wastewater effluents was studied. The effect of different hydrogen peroxide
      concentrations on degradation was investigated. The rate of BPA photolysis in the
      presence of hydrogen peroxide was lower in wastewater effluent than in purified
      water. Phenol, 1,4-dihydroxylbenzene and 1,4-benzoquinone were identified by
      means of HPLC as intermediate products of the photodegradation of bisphenol A. In
      addition, the disappearance of the estrogenic activity of bisphenol A during
      irradiation was shown by the YES test. Based upon the YES test results, there was
      a strong decrease of estrogenic activity of parent compound after 120 min
      irradiation in the presence of hydrogen peroxide.

PMID- 17028064
TI  - UV light assisted decolorization of dark brown colored coffee effluent by photo
      Fenton reaction.
AB  - The photochemical decolorization of coffee effluent has been examined by photo
      Fenton (UV/Fe2+/H2O2) process. Effects of UV light intensity, initial coffee
      concentration, iron dose and H2O2 dose on the color removal of model coffee
      effluent have been investigated. The rate of decolorization increased with
      decreasing initial coffee effluent concentration. It was found that the Fe ion
      dose and UV light intensity enhanced the decolorization rate. The decolorization
      process of coffee effluent could be divided into three established phases. At the
      beginning of the photo-Fenton process, the instantaneous and significant increase
      in color of the solution was found (Phase-I). In the subsequent phase (Phase-II),
      the decolorization rate was initially fast and subsequently decreased. In Phase
      III, the rate was accelerated and then the complete decolorization of model
      coffee effluent was achieved. In order to elucidate the mechanisms of coffee
      effluent color removal process, the concentration changes in Fe3+ and Fe2+
      besides H2O2 were measured during the course of the photo-Fenton process. The
      rate-determining step in Phase-II was the photo-Fenton reaction or photoreduction
      of Fe3+. On the other hand, the decolorization process in Phase-III was highly
      affected by Fenton reaction or decomposition of H2O2 with Fe2+. About 93%
      mineralization of 250 mg L(-1) model coffee effluent was achieved after 250 min.
      A comparative study for TiO2, ZnO and photo-Fenton oxidation processes has been
      also carried out and the photo-Fenton process was found to be the most effective
      for color removal of coffee effluent.

PMID- 17028065
TI  - Characterization of soluble organic matter of waste activated sludge before and
      after thermal pretreatment.
AB  - Microwave (MW) irradiation and conventional heating (CH) at 96 degrees C was
      successful in disrupting the complex waste activated sludge (WAS) floc structure
      and releasing extra- and intra-cellular biopolymers, such as protein and sugars
      from activated sludge flocs into soluble phase along with solubilization of
      particulate chemical oxygen demand (COD). Soluble CODs of CH and MW-irradiated
      WAS were 361+/-45% and 143+/-34% higher and resulted in 475+/-3% and 211+/-2%
      higher cumulative biogas productions (CBP) relative to the control at the end of
      23 days of mesophilic anaerobic digestion, respectively. Ultrafiltration (UF) was
      used to characterize the soluble molecular weight (Mw) distributions of control
      (unpretreated), CH and MW-irradiated WAS. Depending on the Mw fraction, the range
      of substrate volumetric utilization rate increases from anaerobic digesters was
      between 94% and 84% for CH and 26-113% for MW compared to the control for the
      first nine days of the digestion. Digesters treating high Mw (>300 kDa) materials
      resulted in smaller biodegradation rate constants, k, indicating that
      microorganisms require a longer time to utilize high Mw fractions which are most
      likely cell wall fragments and exopolymers.

PMID- 17028066
TI  - Synthesis, biological activity and molecular modelling of new trisubstituted 8
      azaadenines with high affinity for A1 adenosine receptors.
AB  - We describe here the synthesis and biological activity of new 8-azaadenines
      bearing both a phenyl group on C(2) and a 9-benzyl group substituted in the ortho
      position with a Cl or a F atom or a CF(3) group, to verify the synergistic effect
      of a combination of these substitution patterns on binding with the A(1)
      adenosine receptors. In position N(6) aliphatic and cycloaliphatic substituents
      were chosen which had been shown to bind well with the A(1) receptors. Because of
      the high lipophilicity of these kinds of molecules, we also introduced a
      hydroxyalkyl substituent in the same position. The compounds obtained generally
      showed a very good affinity and selectivity for A(1) receptors. Some of the
      compounds showed K(i) in the nanomolar range, one even in the subnanomolar range
      (0.6 M). Molecular docking calculations were performed in order to evaluate the
      interaction energies between the bovine A(1) receptor model and the selected
      ligands, and then to correlate these energies with biological activities of the
      ligands as obtained from the experiments. Molecular docking analysis suggests
      different binding modes towards A(1) receptors that are plausible for these
      ligands.

PMID- 17028071
TI  - Determinants of substrate specificity in KdcA, a thiamin diphosphate-dependent
      decarboxylase.
AB  - Thiamin diphosphate-dependent decarboxylases catalyze the non-oxidative
      decarboxylation of 2-keto carboxylic acids. Although they display relatively low
      sequence similarity, and broadly different range of substrates, these enzymes
      show a common homotetrameric structure. Here we describe a kinetic
      characterization of the substrate spectrum of a recently identified member of
      this class, the branched chain 2-keto acid decarboxylase (KdcA) from Lactococcus
      lactis. In order to understand the structural basis for KdcA substrate
      recognition we developed a homology model of its structure. Ser286, Phe381,
      Val461 and Met358 were identified as residues that appeared to shape the
      substrate binding pocket. Subsequently, site-directed mutagenesis was carried out
      on these residues with a view to converting KdcA into a pyruvate decarboxylase.
      The results show that the mutations all lowered the Km value for pyruvate and
      both the S286Y and F381W variants also had greatly increased values of k(cat)
      with pyruvate as a substrate.

PMID- 17028072
TI  - Nursing education: key issues for the 21st century.
AB  - In this paper, I reflect on what can be learned by engaging in future thinking
      within our discipline, and what implications the results of that thinking may
      have for the development of nursing education. Recognizing the marvelous
      diversity of perspective within our discipline with regard to what will and ought
      to be our future mandate, it seems reasonable to search for some grounding in
      what might ensure that we enter that future wisely. We all know that change is a
      fundamental characteristic of all future projections, and yet that insight seems
      a weak justification for failure to plan. Nurse educators hold a particular
      obligation to ensure that they are preparing the professionals who will take that
      future forward. Although we have always recognized that they must nurse for today
      with an eye on tomorrow, it is inordinately difficult to come to some agreement
      on how we can best bridge that gap within our educational programs and
      strategies. Toward this end, I draw on lessons that can be drawn from our
      professional history as a rich and vibrant context to propose some key issues for
      that future theorizing.

PMID- 17028073
TI  - Education leadership in the clinical health care setting: a framework for nursing
      education development.
AB  - This paper describes how a new framework for clinical nursing education was
      introduced at Counties Manukau District Health Board (CMDHB), New Zealand. The
      project was initiated in response to the significant legislative and post
      registration nursing education changes within New Zealand. The journey of change
      has been a significant undertaking, and has required clear management, strong
      leadership, perseverance and understanding of the organisation's culture. The
      approach taken to managing the change had four stages, and reflects various
      change management models. The first stage, the identification process, identified
      the impetus for change. Creating the vision is the second stage and identified
      what the change would look like within the organisation. To ensure success and to
      guide the process of change a realistic and sustainable vision was developed.
      Implementing the vision was the third stage, and discusses the communication and
      pilot phase of implementing the nursing education framework. Stage four,
      embedding the vision, explores the process and experiences of changing an
      education culture and embedding the vision into an organisation. The paper
      concludes by discussing the importance of implementing robust, consistent,
      strategic and collaborative processes--that reflect and evaluate best educational
      nursing practice.

PMID- 17028074
TI  - Ethically involving students in faculty research.
AB  - Students in nursing education programs have a right to privacy as they engage in
      their learning. At the same time, their faculty may be engaged in nursing
      education research in order to facilitate student learning. These two goals may
      conflict when faculty engage students as participants in nursing education
      research while at the same time facilitating their learning. Faculty as
      researchers with their students may encounter a conflict of interest in
      collecting data for their research while providing learning experiences for the
      same students. As a basic principle, students must be engaged as participants in
      an ethical manner that respects their rights for privacy. In this article, we
      explore the issues of faculty as researchers of their students and suggest
      strategies for addressing these issues.

PMID- 17028075
TI  - Is there a role for higher education in preparing nurses?
AB  - Nurse education is now almost wholly situated within universities
      internationally. However, issues such as the necessity of higher education for
      what is seen as a practical occupation and the question of whether or not nursing
      is a profession arise. Newman viewed universities as places where training was
      given but character was also formed and self-awareness was developed through
      exposure to a wide range of disciplines and this type of education has helped to
      shape other professions. If nursing fulfills the criteria for a profession then
      it requires nurses to be properly educated in higher education. Poor media images
      of nursing, opposition from within and outside of the profession and poor funding
      for research, especially in the UK, where most nurses still do not enter the
      register with a degree, mean that the place of nursing in higher education
      remains on the periphery. Nurses must be competent to practice and higher
      education is not incompatible with the development of competent practitioners.
      However, higher education should take competent practitioners to a higher level
      whereby they become capable: able to respond appropriately in unfamiliar
      situations and to unfamiliar events. This paper argues for the role of higher
      education for nurses in terms of developing capability.

PMID- 17028076
TI  - Education, philosophy and academic practice: nursing studies in the
      posthistorical university.
AB  - This paper is an amended and abridged version of a seminar given at the NET/NEP
      1st Nurse Education International Conference in Vancouver, Canada. The topic of
      the paper arose from our growing concerns about the state of nurse education and
      its position in the university at the start of the twenty-first century. We share
      the fears expressed by Readings that the university has lost its way and is
      increasingly driven by a business agenda and a quest for ever-greater efficiency.
      Our biggest concern is with the impact that the so-called 'posthistorical
      university' is having on the study of nursing, particularly the growing pressure
      on nurse academics to focus their attention and energy on output at the expense
      of process, and on research at the expense of practice and practitioner
      development. We suggest that the solution might lie with Jean-Francois Lyotard's
      notion of postmodern philosophy as a way of opening up debate and, in his words,
      saving the honour of thinking.

PMID- 17028077
TI  - Evolution of anthropogenic aerosols in the coastal town of Salina Cruz, Mexico:
      part II particulate phase chemistry.
AB  - An analysis of atmospheric gases and particles during periods of land and sea
      breezes in a coastal city in southwest Mexico indicates limited removal of total
      particle mass by deposition during periods when the air resides over the ocean.
      The average PM(2.5) mass concentrations for land and sea breeze samples were 25+/
      1.0 and 26+/-1.0 microg m(-3), respectively. The average sum of the ion
      concentrations (NH(4)(+), SO(4)(2-), NO(3)(-), Na(+), Cl(-)) were 10 and 11.8
      microg m(-3) for the samples taken during land and sea breeze periods. The
      average total carbon concentrations were 6.0 and 5.3 microg m(-3) for land and
      sea breeze periods. The mass of sulfate in particles of ocean origin, 3.3+/-2.8
      microg m(-3), is marginally higher than those originating from the land, 2.0+/
      0.8 microg m(-3), presumably as a result of the conversion of SO(2) recirculated
      from the city. The fraction of sulfate, nitrate and ammonium ions in rainwater
      samples is almost a factor of two higher than the fraction measured on filtered
      air samples. The rainwater also contains significant concentrations of elemental
      and organic carbon. This study, although extending over a period of only 15 days,
      with limited chemical samples, suggests that recirculation of anthropogenic
      particles from coastal cities should be taken into consideration when diagnosing
      and predicting air quality in such regions.

PMID- 17028078
TI  - Immune responses generated by Lactobacillus as a carrier in DNA immunization
      against foot-and-mouth disease virus.
AB  - To exploit Lactobacillus acidophilus as a carrier in DNA immunization against
      foot-and-mouth disease virus (FMDV), a recombinant eukaryotic expression plasmid
      (pRc/CMV2-VP1-Rep. 8014) harboring pRc/CMV2 vector, the FMDV VP1 gene, and a
      replication origin from Lactobacillus plantarum ATCC 8014 strain was constructed.
      To detect the VP1 protein, pRc/CMV2-VP1-Rep. 8014 was expressed in PK 15 cells
      and transfected into a L. acidophilus SW1 strain (L. acidophilus SFMD-1). To
      evaluate the immunization effect of L. acidophilus SFMD-1, anti-FMDV VP1
      antibody, T-cell proliferation, antigen-specific delayed-type hypersensitivity
      (DTH), and tissue distribution were investigated using intramuscular,
      intraperitoneal, intranasal, and oral administration delivery routes. The results
      showed that L. acidophilus SFMD-1 was able to elicit a detectable antibody level
      on day 21. The VP1 antibody levels induced by L. acidophilus SFMD-1 and
      commercial inactivated FMDV vaccine rose rapidly to 0.84 and 0.70, respectively,
      by day 42, then sustained a high level by day 49. The route of administration had
      an impact on the magnitude of the systemic antigen-specific IgG responses, with
      intramuscularly applied L. acidophilus SFMD-1 generating the greatest FMDV VP1
      antibody response, followed by intraperitoneal, intranasal, and oral
      administration delivery routes. Using the T-cell proliferation assay, the
      stimulation index of a group immunized with L. acidophilus SFMD-1 reached 2.78
      versus 5.08 in a group immunized with pRc/CMV2-VP1-Rep. 8014 plasmid. Mice
      immunized with L. acidophilus SFMD-1 were able to induce T-cell-mediated antigen
      specific DTH. In addition, the VP1 gene was detected in the muscle, kidney,
      spleen, and heart, but not in the liver. The results demonstrate clearly that
      Lactobacillus as a carrier is a promising approach of DNA vaccination, and is a
      potentially guard against FMDV.

PMID- 17028079
TI  - Germination-independent induction of cellular immune response by Bacillus
      subtilis spores displaying the C fragment of the tetanus toxin.
AB  - Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) on their
      surface have been previously shown to induce the production of specific IgG and
      secretory IgA in mice immunized through the oral or nasal route. Aim of this
      study was to analyze whether these spores were also able to induce cellular
      immunity, and whether such immune response was dependent on spore germination in
      the animal gastro-intestinal tract (GIT). We first developed a germination
      defective strain of B. subtilis unable to produce viable cells inside the mouse
      GIT. Germination-defective and congenic wild-type spores both expressing TTFC on
      their surface were then used to orally immunize Balb/C mice. Both types of spores
      induced spleen and mesenteric lymph nodes cell proliferation as well as
      production of IFNgamma but not of IL-4 and IL-10 in both districts. Our results
      indicate that recombinant spores preferentially induce a strong cell-mediated
      immune response with a Th1 phenotype, independently from their ability to
      germinate in the GIT.

PMID- 17028080
TI  - Molecular characterisation of pneumococcal serotype 16F: Established predominant
      carriage and otitis media serotype in the 7vPCV era.
AB  - Young Australian Aboriginal children in remote communities experience very high
      rates of pneumococcal carriage and otitis media. Prior to introduction of the 7
      valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an
      important type found in nasal and ear discharge swabs. Since commencement of
      pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the
      predominant established serotype in carriage and otitis media in young Aboriginal
      children. BOX typing and multi-locus sequence typing revealed a diverse
      population of serotype 16F strains, and evidence of potential capsule switching
      from a vaccine serotype 4 to a serotype 16F.

PMID- 17028081
TI  - The preventable burden of pneumococcal disease in the developing world.
AB  - The efficacy of pneumococcal conjugate vaccines (PCV) and their remarkable
      success in operational use in North America challenge us to define the burden of
      pneumococcal disease and the likely benefits of PCV use in developing countries.
      Community-based incidence studies of invasive pneumococcal disease (IPD) and
      vaccine probe analyses of efficacy trials suggest there are approximately 814,000
      pneumococcal deaths in children aged <5 years in developing countries each year
      and 1-4 million episodes of pneumococcal pneumonia in Africa alone. PCV will be
      effective where there is a demonstrable burden of IPD attributable to vaccine
      serotypes but herd protection and serotype replacement effects are unpredictable
      given existing knowledge of pneumococcal epidemiology in developing countries.
      Operational use of PCV in well-monitored settings is required to estimate these
      effects.

PMID- 17028082
TI  - The mental health of Chinese immigrants in Birmingham, UK.
AB  - OBJECTIVES: The objectives of this study were to describe the life experiences
      associated with migration to the UK and to explore in-depth information about the
      process of life adjustment to migration and the circumstances of mental health in
      Chinese immigrants living in a large city area. METHOD: A two-part research
      strategy using both quantitative and qualitative methods was employed. In the
      cross-sectional quantitative survey, 113 Chinese respondents completed a
      questionnaire investigating demographic factors, life experiences associated with
      migration, proficiency in the English language and mental health status. In the
      qualitative phase of the research, interviews were conducted with a further 24
      immigrants to explore these factors in more depth. RESULTS: In the questionnaire
      survey, over 60% of the group reported symptoms of poor mental health.
      Qualitative research shows that for those who were employed in catering,
      psychological adjustment was heavily dependent on strong ties with the Chinese
      community and there was minimal contact with the host society. By contrast, those
      concerned with professional development experienced conflict as a result of a
      high perceived need for integration and a recognition of the problems associated
      with this. CONCLUSION: The psychological distress experienced by immigrants of
      Chinese origin continues to be a largely invisible cause for concern.

PMID- 17028084
TI  - What is the extent of prokaryotic diversity?
AB  - The extent of microbial diversity is an intrinsically fascinating subject of
      profound practical importance. The term 'diversity' may allude to the number of
      taxa or species richness as well as their relative abundance. There is
      uncertainty about both, primarily because sample sizes are too small. Non
      parametric diversity estimators make gross underestimates if used with small
      sample sizes on unevenly distributed communities. One can make richness estimates
      over many scales using small samples by assuming a species/taxa-abundance
      distribution. However, no one knows what the underlying taxa-abundance
      distributions are for bacterial communities. Latterly, diversity has been
      estimated by fitting data from gene clone libraries and extrapolating from this
      to taxa-abundance curves to estimate richness. However, since sample sizes are
      small, we cannot be sure that such samples are representative of the community
      from which they were drawn. It is however possible to formulate, and calibrate,
      models that predict the diversity of local communities and of samples drawn from
      that local community. The calibration of such models suggests that migration
      rates are small and decrease as the community gets larger. The preliminary
      predictions of the model are qualitatively consistent with the patterns seen in
      clone libraries in 'real life'. The validation of this model is also confounded
      by small sample sizes. However, if such models were properly validated, they
      could form invaluable tools for the prediction of microbial diversity and a basis
      for the systematic exploration of microbial diversity on the planet.

PMID- 17028085
TI  - Cyanobacterial ecotypes in the microbial mat community of Mushroom Spring
      (Yellowstone National Park, Wyoming) as species-like units linking microbial
      community composition, structure and function.
AB  - We have investigated microbial mats of alkaline siliceous hot springs in
      Yellowstone National Park as natural model communities to learn how microbial
      populations group into species-like fundamental units. Here, we bring together
      empirical patterns of the distribution of molecular variation in predominant mat
      cyanobacterial populations, theory-based modelling of how to demarcate
      phylogenetic clusters that correspond to ecological species and the dynamic
      patterns of the physical and chemical microenvironments these populations inhabit
      and towards which they have evolved adaptations. We show that putative ecotypes
      predicted by the theory-based model correspond well with distribution patterns,
      suggesting populations with distinct ecologies, as expected of ecological
      species. Further, we show that increased molecular resolution enhances our
      ability to detect ecotypes in this way, though yet higher molecular resolution is
      probably needed to detect all ecotypes in this microbial community.

PMID- 17028086
TI  - The spatial scale of genetic differentiation in a model organism: the wild yeast
      Saccharomyces paradoxus.
AB  - Little information is presently available on the factors promoting genetic
      divergence in eukaryotic microbes. We studied the spatial distribution of genetic
      variation in Saccharomyces paradoxus, the wild relative of Saccharomyces
      cerevisiae, from the scale of a few centimetres on individual oak trees to
      thousands of kilometers across different continents. Genealogical analysis of six
      loci shows that isolates from Europe form a single recombining population, and
      within this population genetic differentiation increases with physical distance.
      Between different continents, strains are more divergent and genealogically
      independent, indicating well-differentiated lineages that may be in the process
      of speciation. Such replicated populations will be useful for studies in
      population genomics.

PMID- 17028087
TI  - Biosynthesis of polyunsaturated fatty acids in lower eukaryotes.
AB  - Polyunsaturated fatty acids have important structural roles in cell membranes.
      They are also intermediates in the synthesis of biologically active molecules
      such as eicosanoids, which mediate fever, inflammation, blood pressure and
      neurotransmission. Arachidonic and docosahexaenoic acids are essential components
      of brain tissues and, through their involvement in the development of neural and
      retinal functions, important dietary nutrients for neonatal babies. Lower
      eukaryotes are particularly rich in C20-22 polyunsaturated fatty acids. Fungi and
      marine microalgae are currently used to produce nutraceutic oils. Other protists
      and algae are being studied because of the variability in their enzymes involved
      in polyunsaturated fatty acid biosynthesis. Such enzymes could be used as source
      for the production of transgenic organisms able to synthesize designed oils for
      human diet or, in the case of parasitic protozoa, they might be identified as
      putative chemotherapeutic targets. Polyunsaturated fatty acids can be synthesized
      by two different pathways: an anaerobic one, by using polyketide synthase related
      enzymes, and an aerobic one, which involves the action of elongases and oxygen
      dependent desaturases. Desaturases can be classified into three main types,
      depending on which of the consecutive steps of polyunsaturated fatty acid
      synthesis they are involved with. The enzymes may be specialized to act on:
      saturated substrates (type I); mono- and di-unsaturated fatty acids by
      introducing additional double bonds at the methyl-end site of the existing double
      bonds (type II); or the carboxy half ('front-end') of polyunsaturated ones (type
      III). Type III desaturases require the alternating action of elongases. A
      description of the enzymes that have been isolated and functionally characterized
      is provided, in order to highlight the different pathways found in lower
      eukaryotes.

PMID- 17028088
TI  - A field study investigating the effects of a rebar-tying machine on trunk
      flexion, tool usability and productivity.
AB  - A field study with a before-and-after experimental design was conducted to
      evaluate the potential reduction in the risk of musculoskeletal injuries to
      rodworkers when using an automatic rebar-tying machine. Eleven rodworkers
      participated in this experiment. All dependent variables (trunk posture, rebar
      tying time and responses to a usability questionnaire) were first measured before
      introducing the rebar-tying machine and then after 3 months of usage all
      dependent variables were measured again. The results of the study indicated that
      working with a rebar-tying machine significantly reduced the magnitude, frequency
      and duration of exposure to awkward trunk posture. Tying time was reduced when
      participants used the machine. The usability questionnaire indicated that most
      participants preferred to use the rebar-tying machine for ground-level rebar
      construction. The field study also revealed that the rebar-tying machine is not
      limited to the reinforcing trade. The machine can be used for other purposes,
      such as tying electrical conduit and attaching radiant heat tube to steel mesh.
      Based on trunk posture exposure, rebar-tying time, usability and transferability,
      it is concluded that the rebar-tying machine can be an effective tool to reduce
      the frequency and duration of severe trunk flexion, improve usability and
      increase productivity among concrete reinforcement workers.

PMID- 17028089
TI  - Changes in upper extremity biomechanics across different mouse positions in a
      computer workstation.
AB  - In order to determine differences in biomechanical risk factors across different
      mouse positions within computer workstations a repeated measures laboratory study
      was completed with 30 adults (15 females 15 males). The subjects performed mouse
      intensive tasks during two experiments. One experiment examined three mouse
      positions: a standard mouse (SM) position with the mouse directly to the right of
      the keyboard; a central mouse (CM) position with the mouse between the keyboard
      and the body, positioned in the body's mid-sagittal plane; a high mouse (HM)
      position, which simulated using a keyboard drawer with the mouse on the primary
      work surface. The second experiment compared two mouse positions: the SM position
      and a more central position using a keyboard without a number keypad (NM).
      Electrogoniometers and inclinometers measured wrist and upper arm postures and
      surface electromyography measured muscle activity of four forearm muscles and
      three shoulder muscles. The CM mouse position was found to produce the most
      neutral upper extremity posture across all measures. The HM position produced the
      least neutral posture and resulted in the highest level of muscle activity.
      Compared to the SM position, the NM position reduced wrist extension slightly and
      promoted a more neutral shoulder posture. Little difference in muscle activity
      was observed between the SM and NM positions. In conclusion, of these alternative
      mouse positions, the HM position was the least desirable, whereas the CM position
      reduced overall awkward postures associated with mouse-intensive computer tasks.

PMID- 17028090
TI  - Y chromosome microdeletion in a case with Klinefelter's Syndrome.
AB  - In male infertility, the frequency of genetic factors is high. Klinefelter's
      Syndrome is the most frequent sex chromosomal abnormality detected in male
      infertility. In this study we report a patient diagnosed with Klinefelter's
      Syndrome with a deletion of the Yq interval. The patient was 24-years old with
      primary infertility. Semen analyses carried out in triplicate indicated
      azoospermia. The plasma leutenizing hormone (LH) and follicle stimulating hormone
      (FSH) levels were abnormally high and the testosterone level was lower than the
      usual range. Each of his testes had a volume of 3 cc. Peripheral blood karyotype
      analysis showed Klinefelter's Syndrome (47, XXY) pattern. Polymerase chain
      reaction amplification of DNA was performed using the following primers; AZFa
      (sY81, sY82, sY84), AZFb (sY127, sY142, sY164, RBM1), AZFc (CDY, BPY, sY254,
      sY255, sY277), AZFd (sY152, sY145, sY153). Analysis revealed a single deletion of
      AZFa region (sY84). Deletion of the AZFa region may be an additional factor for
      absolute azoospermia in men with Klinefelter's Syndrome. For individuals with
      Klinefelter's Syndrome who plan to undergo assisted reproduction techniques, Y
      chromosome microdeletion screening can diagnostically be convenient.

PMID- 17028091
TI  - Multivariable difference gel electrophoresis and mass spectrometry: a case study
      on transforming growth factor-beta and ERBB2 signaling.
AB  - Multivariable DIGE/MS was used to investigate proteins altered in expression
      and/or post-translational modification in response to activation of transforming
      growth factor (TGF)-beta receptors in MCF10A mammary epithelial cells
      overexpressing the HER2/Neu (ErbB2) oncogene. Proteome changes were monitored in
      response to exogenous TGF-beta over time (0, 8, 24, and 40 h), and proteins were
      resolved using medium range (pH 4-7) and narrow range (pH 5.3-6.5) isoelectric
      focusing combined with up to 2 mg of protein to allow inspection of lower
      abundance proteins. Triplicate samples were prepared independently and analyzed
      together across multiple DIGE gels using a pooled sample internal standard to
      quantify expression changes with statistical confidence. Unsupervised principle
      component analysis and hierarchical clustering of the individual DIGE proteome
      expression maps provided independent confirmation of distinct expression patterns
      from the individual experiments and demonstrated high reproducibility between
      replicate samples. Fifty-nine proteins (including some isoforms) that exhibited
      significant kinetic expression changes were identified using mass spectrometry
      and database interrogation and were mapped to existing biological networks
      involved in TGF-beta signaling. Several proteins with a potential role in breast
      cancer, such as maspin and cathepsin D, were identified as novel molecules
      associated with TGF-beta signaling.

PMID- 17028093
TI  - The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola
      hepatica.
AB  - OBJECTIVES: The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane
      (OZ78) were determined both in vivo and in vitro. METHODS: Two weeks post
      infection Echinostoma caproni-infected mice were administered single oral doses
      of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with
      50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were
      assessed against untreated control animals. Adult F. hepatica were observed by
      scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3
      days after administration of a single oral dose of 100 mg/kg OZ78 and after in
      vitro exposure to concentrations of 1, 10 and 100 microg/mL OZ78. RESULTS: In the
      E. caproni-mouse model 100% worm burden reductions were achieved with a single
      oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm
      burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica
      recovered from rats 3 days post-treatment displayed feeble activity and some
      flukes had died. Typical features revealed by SEM included extensive blebbing and
      sloughing. Exposure of F. hepatica to 10-100 microg/mL OZ78 in vitro resulted in
      the death of all trematodes. F. hepatica showed focal blebbing and sloughing of
      the tegument at all concentrations investigated. CONCLUSIONS: Our data indicate
      that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a
      sound platform for identification of a synthetic peroxide drug development
      candidate against major trematode infections.

PMID- 17028094
TI  - Testing the mutant selection window hypothesis with Staphylococcus aureus exposed
      to daptomycin and vancomycin in an in vitro dynamic model.
AB  - OBJECTIVES: To extend the mutant selection window (MSW) hypothesis to include
      antibiotics in addition to fluoroquinolones, the pharmacodynamics of daptomycin
      (DAP) and vancomycin (VAN) and their ability to prevent the selection of
      resistant Staphylococcus aureus were studied in an in vitro model that simulates
      antibiotic concentrations below the MIC, between the MIC and the mutant
      prevention concentration (MPC), and above the MPC. METHODS: Two clinical isolates
      of S. aureus, S. aureus 866 (MIC(DAP) 0.35, MIC(VAN) 0.7, MPC(DAP) 1.1, MPC(VAN)
      2.4 mg/L) and S. aureus 10 (MIC(DAP) 1.1, MIC(VAN) 1.3, MPC(DAP) 5.5, MPC(VAN) 11
      mg/L), were exposed for five consecutive days to once-daily daptomycin (half-life
      9 h) and twice-daily vancomycin (half-life 6 h) at the ratio of 24 h area under
      the concentration-time curve (AUC24) to MIC that varied over a 16- to 30-fold
      range. The cumulative antimicrobial effect was expressed by its intensity (I(E)).
      Changes in susceptibility and numbers of surviving organisms on agar plates
      containing 2x and 4x MIC of daptomycin or vancomycin were monitored daily.
      RESULTS: The I(E)-log AUC24/MIC plots were bacterial strain- and antibiotic
      independent. This allowed combination of data obtained with both antibiotics and
      both organisms. Based on the sigmoid relationship between I(E) and the AUC24/MIC
      (r2 = 0.9), the antistaphylococcal effect of the therapeutic doses of daptomycin
      (4 and 6 mg/kg) against a hypothetical S. aureus with MIC equal to the MIC90
      (AUC24/MIC90 380 and 570 h, respectively) was predicted to be similar to the
      effect of two 1 g doses of vancomycin given at a 12 h interval (AUC24/MIC90 200
      h). AUC24/MIC relationships of the final-to-initial MIC ratio and logarithm of
      the ratio of maximal-to-initial numbers of organisms resistant to 2x and 4x MIC
      of daptomycin or vancomycin were bell-shaped and bacterial strain- and antibiotic
      independent. Based on these relationships, an AUC24/MIC ratio that protects
      against the selection of resistant mutants was predicted at > or = 200 h. This
      protective value is less than the AUC24/MIC90s provided by the 4 mg/kg dose and
      considerably less than the 6 mg/kg dose of daptomycin, but it is close to the
      AUC24/MIC90 provided by two 1 g doses of vancomycin. CONCLUSIONS: These findings
      support the MSW hypothesis and suggest comparable antistaphylococcal effects of
      clinically achievable AUC24/MIC90s of daptomycin and vancomycin but slightly
      better prevention against the selection of resistant S. aureus by daptomycin.

PMID- 17028096
TI  - MetaGene: prokaryotic gene finding from environmental genome shotgun sequences.
AB  - Exhaustive gene identification is a fundamental goal in all metagenomics
      projects. However, most metagenomic sequences are unassembled anonymous
      fragments, and conventional gene-finding methods cannot be applied. We have
      developed a prokaryotic gene-finding program, MetaGene, which utilizes di-codon
      frequencies estimated by the GC content of a given sequence with other various
      measures. MetaGene can predict a whole range of prokaryotic genes based on the
      anonymous genomic sequences of a few hundred bases, with a sensitivity of 95% and
      a specificity of 90% for artificial shotgun sequences (700 bp fragments from 12
      species). MetaGene has two sets of codon frequency interpolations, one for
      bacteria and one for archaea, and automatically selects the proper set for a
      given sequence using the domain classification method we propose. The domain
      classification works properly, correctly assigning domain information to more
      than 90% of the artificial shotgun sequences. Applied to the Sargasso Sea
      dataset, MetaGene predicted almost all of the annotated genes and a notable
      number of novel genes. MetaGene can be applied to wide variety of metagenomic
      projects and expands the utility of metagenomics.

PMID- 17028095
TI  - The Saccharomyces cerevisiae RNA polymerase III recruitment factor subunits Brf1
      and Bdp1 impose a strict sequence preference for the downstream half of the TATA
      box.
AB  - Association of the TATA-binding protein (TBP) with its cognate site within
      eukaryotic promoters is key to accurate and efficient transcriptional initiation.
      To achieve recruitment of Saccharomyces cerevisiae RNA polymerase III, TBP is
      associated with two additional factors, Brf1 and Bdp1, to form the initiation
      factor TFIIIB. Previous data have suggested that the structure or dynamics of the
      TBP-DNA complex may be altered upon entry of Brf1 and Bdp1 into the complex. We
      show here, using the altered specificity TBP mutant TBPm3 and an iterative in
      vitro selection assay, that entry of Brf1 and Bdp1 into the complex imposes a
      strict sequence preference for the downstream half of the TATA box. Notably, the
      selected sequence (TGTAAATA) is a perfect match to the TATA box of the RNA
      polymerase III-transcribed U6 small nuclear RNA (SNR6) gene. We suggest that the
      selected T*A base pair step at the downstream end of the 8 bp TBP site may
      provide a DNA flexure that promotes TFIIIB-DNA complex formation.

PMID- 17028097
TI  - Effects of the trinucleotide preceding the self-cleavage site on eggplant latent
      viroid hammerheads: differences in co- and post-transcriptional self-cleavage may
      explain the lack of trinucleotide AUC in most natural hammerheads.
AB  - Eggplant latent viroid (ELVd) can form stable hammerhead structures in its (+)
      and (-) strands. These ribozymes have the longest helices I reported in natural
      hammerheads, with that of the ELVd (+) hammerhead being particularly stable (5/7
      bp are G-C). Moreover, the trinucleotide preceding the self-cleavage site of this
      hammerhead is AUA, which together with GUA also found in some natural
      hammerheads, deviate from the GUC present in most natural hammerheads including
      the ELVd (-) hammerhead. When the AUA trinucleotide preceding the self-cleavage
      site of the ELVd (+) hammerhead was substituted by GUA and GUC, as well as by AUC
      (essentially absent in natural hammerheads), the values of the self-cleavage rate
      constants at low magnesium of the purified hammerheads were: ELVd-(+)-AUC
      approximately ELVd-(+)-GUC>ELVd-(+)-GUA> ELVd-(+)-AUA. However, the ELVd-(+)-AUC
      hammerhead was the catalytically less efficient during in vitro transcription,
      most likely because of the transient adoption of catalytically-inactive
      metastable structures. These results suggest that natural hammerheads have been
      evolutionary selected to function co-transcriptionally, and provide a model
      explaining the lack of trinucleotide AUC preceding the self-cleavage site of most
      natural hammerheads. Comparisons with other natural hammerheads showed that the
      ELVd-(+)-GUC and ELVd-(+)-AUC hammerheads are the catalytically most active in a
      post-transcriptional context with low magnesium.

PMID- 17028098
TI  - A high throughput method for genome-wide analysis of retroviral integration.
AB  - Retroviral and lentiviral vectors integrate their DNA into the host cell genome
      leading to stable transgene expression. Integration preferentially occurs in the
      proximity of active genes, and may in some case disturb their activity, with
      adverse toxic consequences. To efficiently analyze high numbers of lentiviral
      insertion sites in the DNA of transduced cells, we developed an improved high
      throughput method called vector integration tag analysis (VITA). VITA is based on
      the identification of Genomic Tags associated to the insertion sites, which are
      used as signatures of the integration events. We use the capacity of MmeI to
      cleave DNA at a defined distance of its recognition site, in order to generate 21
      bp long tags from libraries of junction fragments between vector and cellular
      DNA. The length of the tags is sufficient in most cases, to identify without
      ambiguity an unique position in the human genome. Concatenation, cloning and
      sequencing of the tags allow to obtain information about 20-25 insertion sites in
      a single sequencing reaction. As a validation of this method, we have
      characterized 1349 different lentiviral vector insertion sites in transduced HeLa
      cells, from only 487 sequencing reactions, with a background of <2% false
      positive tags.

PMID- 17028099
TI  - DeepSAGE--digital transcriptomics with high sensitivity, simple experimental
      protocol and multiplexing of samples.
AB  - Digital transcriptomics with pyrophosphatase based ultra-high throughput DNA
      sequencing of di-tags provides high sensitivity and cost-effective gene
      expression profiling. Sample preparation and handling are greatly simplified
      compared to Serial Analysis of Gene Expression (SAGE). We compare DeepSAGE and
      LongSAGE data and demonstrate greater power of detection and multiplexing of
      samples derived from potato. The transcript analysis revealed a great abundance
      of up-regulated potato transcripts associated with stress in dormant potatoes
      compared to harvest. Importantly, many transcripts were detected that cannot be
      matched to known genes, but is likely to be part of the abiotic stress-response
      in potato.

PMID- 17028100
TI  - Expression of C-terminal deleted p53 isoforms in neuroblastoma.
AB  - The tumor suppressor gene, p53, is rarely mutated in neuroblastomas (NB) at the
      time of diagnosis, but its dysfunction could result from a nonfunctional
      conformation or cytoplasmic sequestration of the wild-type p53 protein. However,
      p53 mutation, when it occurs, is found in NB tumors with drug resistance acquired
      over the course of chemotherapy. As yet, no study has been devoted to the
      function of the specific p53 mutants identified in NB cells. This study includes
      characterization and functional analysis of p53 expressed in eight cell lines:
      three wild-type cell lines and five cell lines harboring mutations. We identified
      two transcription-inactive p53 variants truncated in the C-terminus, one of which
      corresponded to the p53beta isoform recently identified in normal tissue by
      Bourdon et al. [J. C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A.
      Diot, D. P. Xirodimas, M. K. Saville and D. P. Lane (2005) Genes Dev., 19, 2122
      2137]. Our results show, for the first time, that the p53beta isoform is the only
      p53 species to be endogenously expressed in the human NB cell line SK-N-AS,
      suggesting that the C-terminus truncated p53 isoforms may play an important role
      in NB tumor development.

PMID- 17028101
TI  - Functional characterization of a 48 kDa Trypanosoma brucei cap 2 RNA
      methyltransferase.
AB  - Kinetoplastid mRNAs possess a unique hypermethylated cap 4 structure derived from
      the standard m7GpppN cap structure, with 2'-O methylations on the first four
      ribose sugars and additional base methylations on the first adenine and the
      fourth uracil. While the enzymes responsible for m7GpppN cap 0 formations has
      been characterized in Trypanosoma brucei, the mechanism of cap 4 methylation and
      the role of the hypermethylated structure remain unclear. Here, we describe the
      characterization of a 48 kDa T.brucei 2'-O nucleoside methyltransferase (TbCom1).
      Recombinant TbCom1 transfers the methyl group from S-adenosylmethionine (AdoMet)
      to the 2'-OH of the second nucleoside of m7GpppNpNp-RNA to form m7GpppNpNmp-RNA.
      TbCom1 is also capable of converting cap 1 RNA to cap 2 RNA. The methyl transfer
      reaction is dependent on the m7GpppN cap, as the enzyme does not form a stable
      interaction with GpppN-terminated RNA. Mutational analysis establishes that the
      TbCom1 and vaccinia virus VP39 methyltransferases share mechanistic similarities
      in AdoMet- and cap-recognition. Two aromatic residues, Tyr18 and Tyr187, may
      participate in base-stacking interactions with the guanine ring of the cap, as
      the removal of each of these aromatic side-chains abolishes cap-specific RNA
      binding.

PMID- 17028102
TI  - RusA Holliday junction resolvase: DNA complex structure--insights into
      selectivity and specificity.
AB  - We have determined the structure of a catalytically inactive D70N variant of the
      Escherichia coli RusA resolvase bound to a duplex DNA substrate that reveals
      critical protein-DNA interactions and permits a much clearer understanding of the
      interaction of the enzyme with a Holliday junction (HJ). The RusA enzyme cleaves
      HJs, the fourway DNA branchpoints formed by homologous recombination, by
      introducing symmetrical cuts in the phosphodiester backbone in a Mg2+ dependent
      reaction. Although, RusA shows a high level of selectivity for DNA junctions,
      preferring to bind fourway junctions over other substrates in vitro, it has also
      been shown to have appreciable affinity for duplex DNA. However, RusA does not
      show DNA cleavage activity with duplex substrates. Our structure suggests the
      possible basis for structural selectivity as well as sources of the sequence
      specificity observed for DNA cleavage by RusA.

PMID- 17028103
TI  - August 2003 heat wave in France: risk factors for death of elderly people living
      at home.
AB  - The August 2003 heat wave in France resulted in many thousands of excess deaths
      particularly of elderly people. Individual and environmental risk factors for
      death among the community-dwelling elderly were identified. We conducted a case
      control survey and defined cases as people aged 65 years and older who lived at
      home and died from August 8 through August 13 from causes other than accident,
      suicide, or surgical complications. Controls were matched with cases for age,
      sex, and residential area. Interviewers used questionnaires to collect data.
      Satellite pictures provided profiles of the heat island characteristics around
      the homes. Lack of mobility was a major risk factor along with some pre-existing
      medical conditions. Housing characteristics associated with death were lack of
      thermal insulation and sleeping on the top floor, right under the roof. The
      temperature around the building was a major risk factor. Behaviour such as
      dressing lightly and use of cooling techniques and devices were protective
      factors. These findings suggest people with pre-existing medical conditions were
      likely to be vulnerable during heat waves and need information on how to adjust
      daily routines to heat waves. In the long term, building insulation and urban
      planning must be adapted to provide protection from possible heat waves.

PMID- 17028104
TI  - How to change environmental conditions for health.
AB  - Since the Lalonde report, contemporary public-health theory has given steadily
      more attention to the role of environments in influencing health status.
      Environments, both social and physical, influence health directly or through
      complex interactions with behavior, genetics and health-care systems. They are
      also important for public-health because environments are the complex systems
      through which people are both empowered and exercise their empowerment. If public
      health professionals are to play a significant role in influencing environments
      for health, they need analytical instruments that enable them to link specific
      environmental conditions with the actions necessary to improve them. These
      instruments must also enable public-health professionals to identify points of
      leverage for stimulating key actors to take the actions necessary to make
      environments more promoting of health. This article first presents one such
      analytical instrument. Then, building on examples relating to socio-economic
      health inequities, the analytical instrument is applied to reveal how it can add
      value to health professionals' effectiveness in planning interventions for more
      health-promoting environments.

PMID- 17028105
TI  - Physical activity to prevent obesity in young children: cluster randomised
      controlled trial.
AB  - OBJECTIVE: To assess whether a physical activity intervention reduces body mass
      index in young children. DESIGN: Cluster randomised controlled single blinded
      trial over 12 months. SETTING: Thirty six nurseries in Glasgow, Scotland.
      PARTICIPANTS: 545 children in their preschool year, mean age 4.2 years (SD 0.2)
      at baseline. INTERVENTION: Enhanced physical activity programme in nursery (three
      30 minute sessions a week over 24 weeks) plus home based health education aimed
      at increasing physical activity through play and reducing sedentary behaviour.
      MAIN OUTCOME MEASURE: Body mass index, expressed as a standard deviation score
      relative to UK 1990 reference data. Secondary measures were objectively measured
      physical activity and sedentary behaviour; fundamental movement skills; and
      evaluation of the process. RESULTS: Group allocation had no significant effect on
      the primary outcome measure at six and 12 months or on measures of physical
      activity and sedentary behaviour by accelerometry. Children in the intervention
      group had significantly higher performance in movement skills tests than control
      children at six month follow-up (P=0.0027; 95% confidence interval 0.3 to 1.3)
      after adjustment for sex and baseline performance. CONCLUSIONS: Physical activity
      can significantly improve motor skills but did not reduce body mass index in
      young children in this trial. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN36363490.

PMID- 17028107
TI  - Gas diffusion and alveolar-capillary unit in chronic heart failure.
AB  - AIMS: Alveolar gas diffusion (DLCO) is impaired in chronic heart failure (CHF).
      Diffusion depends on membrane diffusion (DM) and the amount of blood
      participating in gas exchange (VC). How DM, VC, and the alveolar-capillary unit
      behave in relationship to CHF severity is unknown. METHODS AND RESULTS: We
      measured pulmonary function, including DLCO, DM, VC, and alveolar volume (VA), in
      191 CHF patients in NYHA class I-III. CHF patients were grouped accordingly to
      peak exercise oxygen uptake (pVO(2)): group <12 mL/min/kg (n=24), group 12-16
      (n=76), group 16-20 (n=64), and group >20 (n=27). DLCO, DM, VC, and VA were
      lowest in severe CHF and were linearly related to pVO(2) (DLCO, r=0.577, P<0.001;
      DM, r=0.490, P<0.001; VC, r=0.216, P<0.01; VA, r=0.565, P<0.01). DM/VC ratio, an
      index of the alveolar-capillary unit efficiency, was higher in group <12 (0.49+/
      0.39 mL/min/mmHg/mL) and >20 (0.46+/-0.29), compared with 12-16 (0.34+/-0.19) and
      16-20 (0.35+/-0.17). CONCLUSION: DLCO progressively worsens as CHF severity
      increases due to reduction in lung tissue participating to gas exchange (low VC
      and VA). In severe CHF, the few working alveolar-capillary units are the most
      efficient as shown by the high DM/VC. This is useful for maintaining gas exchange
      efficiency in severe CHF.

PMID- 17028106
TI  - Cochrane reviews compared with industry supported meta-analyses and other meta
      analyses of the same drugs: systematic review.
AB  - OBJECTIVE: To compare the methodological quality and conclusions in Cochrane
      reviews with those in industry supported meta-analyses and other meta-analyses of
      the same drugs. DESIGN: Systematic review comparing pairs of meta-analyses that
      studied the same two drugs in the same disease and were published within two
      years of each other. DATA SOURCES: Cochrane Database of Systematic Reviews (2003,
      issue 1), PubMed, and Embase. DATA EXTRACTION: Two observers independently
      extracted data and used a validated scale to judge the methodological quality of
      the reviews. RESULTS: 175 of 1596 Cochrane reviews had a meta-analysis that
      compared two drugs. Twenty four meta-analyses that matched the Cochrane reviews
      were found: eight were industry supported, nine had undeclared support, and seven
      had no support or were supported by non-industry sources. On a 0-7 scale, the
      median quality score was 7 for Cochrane reviews and 3 for other reviews (P <
      0.01). Compared with industry supported reviews and reviews with undeclared
      support, Cochrane reviews had more often considered the potential for bias in the
      review--for example, by describing the method of concealment of allocation and
      describing excluded patients or studies. The seven industry supported reviews
      that had conclusions recommended the experimental drug without reservations,
      compared with none of the Cochrane reviews (P = 0.02), although the estimated
      treatment effect was similar on average (z = 0.46, P = 0.64). Reviews with
      undeclared support and reviews with not for profit support or no support had
      conclusions that were similar in cautiousness to the Cochrane reviews.
      CONCLUSIONS: Industry supported reviews of drugs should be read with caution as
      they were less transparent, had few reservations about methodological limitations
      of the included trials, and had more favourable conclusions than the
      corresponding Cochrane reviews.

PMID- 17028108
TI  - Platelets and heart failure.
AB  - Heart failure is associated with increased risk of venous thromboembolism,
      stroke, and sudden death. Platelet abnormalities have been well described in
      heart failure but the significance of platelets in contributing to the
      thromboembolic complications of heart failure remains uncertain. Furthermore, the
      role of antiplatelet agents in heart failure remains unclear. This review will
      focus on platelet activation and the role of platelet dysfunction in heart
      failure, with particular regard to pathophysiology and outcome. The effects of
      heart failure therapeutics on platelet function and antiplatelet therapy in heart
      failure will also be discussed.

PMID- 17028109
TI  - Sweet and sour coronary heart disease: results from the China Heart Survey.

PMID- 17028110
TI  - Toll the bell for another genetic association?

PMID- 17028111
TI  - Guidelines on the management of stable angina pectoris.

PMID- 17028113
TI  - A major susceptibility locus for HTLV-1 infection in childhood maps to chromosome
      6q27.
AB  - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is a human oncoretrovirus
      causing adult T-cell leukemia/lymphoma and chronic neuromyelopathy. We previously
      showed by segregation analysis that a dominant gene controls HTLV-1 infection
      through breast-feeding in children of African origin. Here, we report the mapping
      of this locus by a genome-wide linkage analysis based on the genetic model
      provided by segregation analysis. Five pedigrees of African origin with HTLV-1
      seropositive children were included in the study. Significant evidence for
      linkage (LOD score of 3.36, P=0.00004) was obtained for chomosomal region 6q27
      when using the robust analysis including only HTLV-1-infected subjects. When HTLV
      1 seronegative children born to infected mothers were added in the analysis, a
      maximum LOD score of 2.79 (P=0.0002) was obtained for chomosome 2p25. This result
      was mostly due to the largest pedigree of our sample, which alone gave a LOD
      score of 2.90 (P=0.00013). We further excluded the role of exonic variants of two
      candidate genes located in the linked regions, CCR6 (chemokine receptor 6) in
      6q27 and ID2 (inhibitor of DNA binding 2) in 2p25. Our results, mapping a major
      susceptibility locus to chromosome 6q27 and suggesting genetic heterogeneity with
      another locus at 2p25, pave the way to the determination of the molecular basis
      of predisposition to HTLV-1 infection in children.

PMID- 17028112
TI  - Analysis of Nsdhl-deficient embryos reveals a role for Hedgehog signaling in
      early placental development.
AB  - The X-linked Nsdhl gene encodes a sterol dehydrogenase involved in cholesterol
      biosynthesis. Mutations in this gene cause the male lethal phenotypes in human
      CHILD syndrome and bare patches (Bpa) mice. Affected male embryos for several
      mutant Nsdhl alleles die in mid-gestation with a thin and poorly vascularized
      placental labyrinth. The timing and specific abnormalities noted suggest a defect
      in one or more developmental signaling pathways as a possible mechanism. Here, we
      examined the possible involvement of the hedgehog signaling pathway in the
      placental pathology of Nsdhl mutants using a transgenic mouse line
      (Ptch1(tm1Mps)) that contains a lacZ reporter under the control of the promoter
      for Ptch1, the gene that encodes the major hedgehog receptor. We demonstrate
      expression of Ptch1 in allantoic mesoderm of the placenta from wild-type mid
      gestation embryos. The evidence suggests that the signaling is induced by Indian
      hedgehog that is produced by distal (ectoplacental) visceral endoderm cells that
      migrate into the allantoic mesoderm before embryonic day 10.0. Using a
      ubiquitously expressed, X-linked lacZ transgene that undergoes normal X
      inactivation, we demonstrate that the placental defects in Nsdhl/+ female embryos
      are non-cell autonomous. Further, affected placentas from mutant Nsdhl(Bpa-8H)
      male embryos demonstrate markedly decreased or no Ptch1-lacZ staining and no
      migration of Ihh expressing cells into the developing placenta. These data
      strongly implicate the hedgehog signaling pathway in the pathogenesis of the
      placental defects in NSDHL deficiency and provide evidence for a role for the
      hedgehog pathway in the development of a functional mammalian placenta.

PMID- 17028114
TI  - A functional M196R polymorphism of tumour necrosis factor receptor type 2 is
      associated with systemic lupus erythematosus: a case-control study and a meta
      analysis.
AB  - OBJECTIVES: To perform a case-control study of a functional M196R polymorphism of
      tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a
      meta-analysis of all published reports on the polymorphism to investigate the
      association of the M196R polymorphism of TNF-RII with systemic lupus
      erythematosus (SLE). METHODS: The functional M196R polymorphism of TNF-RII was
      genotyped by using polymerase chain reaction combined with the subsequent single
      strand conformation polymorphism (PCR-SSCP) analysis for screening, followed by
      nucleotide sequencing for confirmation. A total of 331 patients and 359 controls
      were subjected to a case-control study. A meta-analysis of the available case
      control studies including all published data as well as our own data was
      performed to investigate the association of the functional M196R polymorphism of
      TNF-RII with SLE. RESULTS: Our case-control study did not show any significant
      association of a functional M196R polymorphism of TNF-RII with SLE, although
      there was a trend towards association. A meta-analysis of seven case-control
      studies in eight different ethnic populations including our own showed that
      196M/R and 196R/R genotypes combined was significantly associated with an
      increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to
      1.60; p = 0.02). Stratification by ethnicity showed a more significant
      association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI
      1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in
      Caucasians. CONCLUSIONS: The 196R allele of the functional M196R polymorphism of
      TNF-RII is a risk factor for SLE, especially in the Asian population.

PMID- 17028115
TI  - Lumbar disc degeneration: association between osteophytes, end-plate sclerosis
      and disc space narrowing.
AB  - BACKGROUND: Lumbar disc degeneration is characterised radiologically by the
      presence of osteophytes, end-plate sclerosis and disc space narrowing. AIM: To
      determine the strength of the association between increasing severity of
      combinations of these features in a population sample of men and women. METHODS:
      Men and women aged >or=50 years were recruited from a primary care-based
      community health index in Aberdeen, UK. Participants had lateral spinal
      radiographs performed according to a standard protocol. The intervertebral disc
      spaces (L1/2-L4/5) were evaluated for the presence of anterior osteophytes, end
      plate sclerosis and disc space narrowing using a graded semiquantitative score
      (grade 0-3). Log linear modelling was used to determine the associations
      (pairwise) between increasing severity of these features, with the results
      expressed as beta coefficients and 95% confidence intervals (CIs). RESULTS: There
      were 286 men (mean age 65.3 years) and 299 women (mean age 65.2 years) with
      spinal radiographs, yielding a total of 2340 assessable lumbar vertebral levels.
      In all, 73% of vertebral levels had evidence of osteophytes, 26% of sclerosis and
      37% of disc space narrowing. Increasing severity of osteophyte grade was
      associated with an increasing severity both of sclerosis and of disc space
      narrowing, whereas the severity of sclerosis was associated with the severity of
      narrowing. This was true at all vertebral levels. The strongest association,
      however, was between osteophytes and sclerosis (beta coefficient = 2.7, 95% CI
      2.4 to 3.1). For sclerosis and narrowing the beta coefficient was 1.9 (95% CI 1.7
      to 2.1), whereas for osteophytes and narrowing the beta coefficient was much
      weaker at 1.2 (95% CI 1.1 to 1.3). There was no important influence of vertebral
      level on any of these associations. CONCLUSION: The association between
      increasing severity of osteophytes and end-plate sclerosis is stronger than for
      other combinations of radiographic features of lumbar disc degeneration.

PMID- 17028116
TI  - Diagnosis and treatment of dural carotid-cavernous fistulas: a consecutive series
      of 27 patients.
AB  - OBJECTIVES: To report clinical characteristics, angiographical findings and
      results of endovascular treatment of patients presenting with dural carotid
      cavernous fistulas (DCCFs). METHOD: Retrospective analysis of 27 consecutive
      patients with DCCF referred to a specialised interventional neuroradiology
      department. RESULTS: Orbital and neuro-ophthalmological symptoms were the most
      common clinical presentation at diagnosis (n = 25). The venous drainage of the
      fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the
      contralateral cavernous sinus in 6 and a leptomeningeal vein in 5 patients.
      Thrombosis of at least one petrosal sinus was found in 23 patients. 7 patients
      did not receive endovascular treatment: 3 had spontaneous DCCF obliteration, and
      4 had only minor clinical symptoms and no leptomeningeal venous drainage on an
      angiogram. 20 patients received endovascular treatment via either a transvenous
      (n = 16) or a transarterial approach (n = 4). Complete occlusion of the fistula
      was obtained in 14 of 16 (87%) patients treated by the transvenous approach and
      in 1 of 4 (25%) patients treated by the transarterial approach. 16 patients had
      early clinical improvement after endovascular treatment. One patient had a
      cerebral haemorrhage after transvenous embolisation of a DCCF with leptomeningeal
      drainage. On follow-up, all patients treated by the transarterial route remained
      symptomatic, whereas 10 of 14 (71%) patients cured by the transvenous route were
      asymptomatic. CONCLUSIONS: Transvenous embolisation is a safe and efficient
      endovascular approach to treat patients with DCCF. However, this technique
      requires a long learning curve.

PMID- 17028117
TI  - Functional connectivity of the prefrontal cortex in Huntington's disease.
AB  - BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that
      results in deterioration and atrophy of various brain regions. AIM: To assess the
      functional connectivity between prefrontal brain regions in patients with
      Huntington's disease, compared with normal controls, using functional magnetic
      resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease
      and 17 matched controls performed a Simon task that is known to activate lateral
      prefrontal and anterior cingulate cortical regions. The functional connectivity
      was hypothesised to be impaired in patients with Huntington's disease between
      prefrontal regions of interest, selected from both hemispheres, in the anterior
      cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a
      dynamic increase in interhemispheric functional connectivity during task
      performance, compared with the baseline state; patients with Huntington's
      disease, however, showed no such increase in prefrontal connectivity. Overall,
      patients with Huntington's disease showed significantly impaired functional
      connectivity between anterior cingulate and lateral prefrontal regions in both
      hemispheres compared with controls. Furthermore, poor task performance was
      predicted by reduced connectivity in patients with Huntington's disease between
      the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding
      represents a loss of synchrony in activity between prefrontal regions in patients
      with Huntington's disease when engaged in the task, which predicted poor task
      performance. Results show that functional interactions between critical
      prefrontal regions, necessary for cognitive performance, are compromised in
      Huntington's disease. It is speculated whether significantly greater levels of
      activation in patients with Huntington's disease (compared with controls)
      observed in several brain regions partially compensate for the otherwise
      compromised interactions between cortical regions.

PMID- 17028118
TI  - Corpus callosum atrophy is associated with mental slowing and executive deficits
      in subjects with age-related white matter hyperintensities: the LADIS Study.
AB  - BACKGROUND: Previous research has indicated that corpus callosum atrophy is
      associated with global cognitive decline in neurodegenerative diseases, but few
      studies have investigated specific cognitive functions. OBJECTIVE: To investigate
      the role of regional corpus callosum atrophy in mental speed, attention and
      executive functions in subjects with age-related white matter hyperintensities
      (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age
      related WMH were examined with a detailed neuropsychological assessment and
      quantitative magnetic resonance imaging. The relationships of the total corpus
      callosum area and its subregions with cognitive performance were analysed using
      multiple linear regression, controlling for volume of WMH and other confounding
      factors. RESULTS: Atrophy of the total corpus callosum area was associated with
      poor performance in tests assessing speed of mental processing--namely, trail
      making A and Stroop test parts I and II. Anterior, but not posterior, corpus
      callosum atrophy was associated with deficits of attention and executive
      functions as reflected by the symbol digit modalities and digit cancellation
      tests, as well as by the subtraction scores in the trail making and Stroop tests.
      Furthermore, semantic verbal fluency was related to the total corpus callosum
      area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to
      contribute to cognitive decline independently of age, education, coexisting WMH
      and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe
      mediated executive functions and attention, whereas overall corpus callosum
      atrophy is associated with the slowing of processing speed.

PMID- 17028119
TI  - A magnetic resonance imaging study of patients with Parkinson's disease with mild
      cognitive impairment and dementia using voxel-based morphometry.
AB  - BACKGROUND: Dementia is common in Parkinson's disease, but the underlying brain
      pathology is not yet fully understood. AIM: To examine the changes in the brain
      of patients with Parkinson's disease with mild cognitive impairment (MCI) and
      dementia, using structural magnetic resonance imaging. METHODS: Using voxel-based
      morphometry, the grey matter atrophy on brain images of patients with Parkinson's
      disease and dementia (PDD; n = 16) and Parkinson's disease without dementia
      (PDND; n = 20), and healthy elderly subjects (n = 20) was studied. In the PDND
      group, 12 subjects had normal cognitive status and 8 had MCI. Standardised rating
      scales for motor, cognitive and psychiatric symptoms were used. RESULTS:
      Widespread areas of cortical atrophy were found in patients with PDD compared
      with normal controls (in both temporal and frontal lobes and in the left parietal
      lobe). Grey matter reductions were found in frontal, parietal, limbic and
      temporal lobes in patients with PDD compared with those with PDND. In patients
      with PDND with MCI, areas of reduced grey matter in the left frontal and both
      temporal lobes were found. CONCLUSION: These findings show that dementia in
      Parkinson's disease is associated with structural neocortical changes in the
      brain, and that cognitive impairment in patients with PDND may be associated with
      structural changes in the brain. Further studies with larger groups of patients
      are needed to confirm these findings.

PMID- 17028120
TI  - Fatal encephalopathy after an isolated overdose of cocaine.

PMID- 17028121
TI  - Acute disseminated encephalomyelitis: a follow-up study in Taiwan.
AB  - BACKGROUND: Acute-disseminated encephalomyelitis (ADEM) is a demyelinating
      disorder of the central nervous system, whose epidemiology, clinical
      presentations and functional outcome are incompletely understood in Asian
      populations. OBJECTIVE: To assess the clinical presentations, predisposing
      factors and functional outcome of ADEM in Taiwan. METHODS: 50 patients initially
      diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005.
      Diagnosis of ADEM or multiple sclerosis was established during a follow-up period
      of 2-120 months. 8 adult patients were noted to have taken the immunomodulatory
      drug, levamisole, within 3 months before onset of symptoms. The remaining 42
      patients (male, 17; female, 25) were categorised by age as children (<16 years, n
      = 12), young adults (16-49 years, n = 21) and elderly adults (> or =50 years, n =
      9). The clinical manifestations, predisposing factors and radiological findings
      were compared between different age groups and adult patients with or without
      levamisole use. Functional outcome was compared by a log-rank test. RESULTS:
      Preceding upper respiratory tract infection was evident in 21 (50%) patients and
      only one young-adult patient had received Rubella vaccine immunisation. The
      frequency of fever was higher in children (p = 0.04) and psychiatric symptoms
      were more prevalent in elderly patients (p = 0.03). Functional recovery was
      faster in children than in adults (p = 0.002). Initial Expanded Disability Status
      Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were
      associated with poor outcome (modified Rankin scale > or =2). After a mean (SD)
      follow-up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3
      (25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability,
      radiological and cerebrospinal fluid findings did not differ between patients
      with and without levamisole use. One elderly adult patient previously receiving
      levamisole developed multiple sclerosis of relapse-remitting type after a mean
      follow-up period of 36.9 months. CONCLUSION: The clinical presentations,
      functional outcome and risk of developing multiple sclerosis differed between
      different age groups. Functional recovery was faster in children than in adults.
      Poor functional outcome was related to initial high Expanded Disability Status
      Scale score and absence of fever.

PMID- 17028122
TI  - Temporal changes in cerebral tissue oxygenation with cerebrovascular pressure
      reactivity in severe traumatic brain injury.
AB  - OBJECTIVE: To investigate the temporal relationship between cerebrovascular
      pressure reactivity and brain tissue oxygenation in patients with severe head
      injury. METHODS: In 40 patients, brain tissue oxygenation and intracranial
      pressure were monitored. Time-averaged values for intracranial pressure (ICP),
      mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain tissue
      oxygenation (PtiO2) were computed. The pressure reactivity index (PRx) was
      calculated. The mean values of the variables were obtained at the 6-h and 72-h
      post-injury time points, and the difference between the two time points for each
      of the variables was denoted as delta (delta). RESULTS: Of the 40 patients, 32
      were survivors and 8 were non-survivors. Statistically significant differences
      were present between these two groups with regard to deltaMAP (p = 0.013), ICP at
      6 h (p = 0.027), CPP at 72 h (p = 0.018), deltaCPP (p = 0.033), PRx at 6 h (p =
      0.029), PRx at 72 h (p = 0.002), PtiO2 at 72 h (p < 0.0005) and deltaPtiO2 (p =
      0.023) values, reflecting an improvement with time in survivors and a
      deterioration with time in non-survivors. In non-survivors, the magnitude of
      change in PtiO2 and CPP with time correlated in a negative linear fashion (p =
      0.042 and 0.029, respectively) with the change in PRx with time, whereas no such
      relationship was seen in survivors. CONCLUSION: The severity of brain tissue
      oxygenation derangement correlates with increasing cerebrovascular
      dysautoregulation in patients succumbing to severe head injury, supporting the
      utility of PRx as a monitoring variable and the rationale for a target-driven
      approach to head injury management.

PMID- 17028123
TI  - A case of intrahepatic cholangiocarcinoma involving the proper hepatic artery.

PMID- 17028124
TI  - International comparisons of cumulative risk of oesophagus cancer, from cancer
      incidence in five continents Vol. VIII.

PMID- 17028125
TI  - Outpatient liver biopsy: a prospective evaluation of 500 cases.

PMID- 17028126
TI  - Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin
      treatment for Helicobacter pylori eradication: the HYPER Study.
AB  - BACKGROUND: Triple therapy is recommended for Helicobacter pylori eradication,
      yet consensus on the duration of treatment is lacking. AIM: To compare the
      efficacy and safety of 1- and 2-week regimens of omeprazole, amoxicillin and
      clarithromycin in a large, multicentre, double-blind and randomised study.
      METHODS: A total of 909 H pylori-positive patients with duodenal ulcer, enrolled
      in 81 endoscopy units in Italy, were randomised to receive omeprazole,
      amoxicillin and clarithromycin for either 1 week (OAC1W) or 2 weeks (OAC2W) or
      omeprazole and amoxicillin for 2 weeks. H pylori eradication was assessed by
      histological examination and carbon-13 urea breath test 4 weeks after treatment.
      RESULTS: Both the intention-to-treat (ITT; n = 907) and per protocol (PP; n =
      661) analyses showed no significant differences between the eradication rates of
      OAC1W (ITT 79.7%; PP 83.6%) and OAC2W (ITT 81.7%; PP 84.9%; ITT p = 0.53; PP p =
      0.71). Both triple omeprazole, amoxicillin and clarithromycin regimens gave
      significantly higher eradication rates compared with omeprazole and amoxicillin
      treatment (ITT 44.6%; PP 42.8%; p<0.001). Poor compliance was reported in 18.6%,
      17.3% and 15.1% (p = 0.51) of patients for OAC2W, OAC1W and omeprazole and
      amoxicillin, respectively. Adverse events occurred in 9.9% and 9.6% (p = 0.88) of
      patients for OAC2W and OAC1W, respectively, and in 5.9% for omeprazole and
      amoxicillin (p = 0.11). CONCLUSIONS: 1-week and 2-week triple treatments for H
      pylori eradication are similar in terms of efficacy, safety and patient
      compliance.

PMID- 17028127
TI  - Ulcerative colitis: no rise in mortality in a European-wide population based
      cohort 10 years after diagnosis.
AB  - BACKGROUND: Population based studies have revealed varying mortality for patients
      with ulcerative colitis but most have described patients from limited
      geographical areas who were diagnosed before 1990. AIMS: To assess overall
      mortality in a European cohort of patients with ulcerative colitis, 10 years
      after diagnosis, and to investigate national ulcerative colitis related mortality
      across Europe. METHODS: Mortality 10 years after diagnosis was recorded in a
      prospective European-wide population based cohort of patients with ulcerative
      colitis diagnosed in 1991-1993 from nine centres in seven European countries.
      Expected mortality was calculated from the sex, age and country specific
      mortality in the WHO Mortality Database for 1995-1998. Standardised mortality
      ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: At
      follow-up, 661 of 775 patients were alive with a median follow-up duration of 123
      months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133))
      occurred compared with an expected 67. The overall mortality risk was no higher:
      SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to
      1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a
      slightly higher risk in older age groups. For disease specific mortality, a
      higher SMR was found only for pulmonary disease. Mortality by European region was
      SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for
      the south. CONCLUSIONS: Higher mortality was not found in patients with
      ulcerative colitis 10 years after disease onset. However, a significant rise in
      SMR for pulmonary disease, and a trend towards an age related rise in SMR, was
      observed.

PMID- 17028128
TI  - High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in
      inflammatory bowel disease.
AB  - BACKGROUND: It is not clear which species of bacteria may be involved in
      inflammatory bowel disease (IBD). One way of determining which bacteria might be
      likely candidates is to use culture-independent methods to identify
      microorganisms that are present in diseased tissues but not in controls. AIMS:
      (1) To assess the diversity of microbial communities of biopsy tissue using
      culture-independent methods; (2) to culture the bacteria found in the tissues of
      patients with IBD but not in the controls; (3) to identify potential virulence
      factors associated with cultured bacteria. METHODS: 84 biopsy specimens were
      collected from 15 controls, 13 patients with Crohn's disease (CD) and 19 patients
      with ulcerative colitis (UC) from a population-based case-control study.
      Ribosomal intergenic spacer analysis (RISA) was conducted to identify unique DNA
      bands in tissues from patients with CD and UC that did not appear in controls.
      RESULTS: RISA followed by DNA sequencing identified unique bands in biopsy
      specimens from patients with IBD that were classified as Escherichia coli.
      Targeted culture showed a significantly (p<0.05) higher number of
      Enterobacteriaceae in specimens from patients with IBD. The B2+D phylogenetic
      group, serine protease autotransporters (SPATE) and adherence factors were more
      likely to be associated with tissues from patients with UC and CD than with
      controls. CONCLUSIONS: The abundance of Enterobacteriaceae is 3-4 logs higher in
      tissues of patients with IBD and the B2+D phylogenetic groups are more prevalent
      in patients with UC and CD. The B2+D phylogenetic groups are associated with
      SPATE and adherence factors and may have a significant role in disease aetiology.

PMID- 17028129
TI  - Ultrasonic storage modulus as a novel parameter for analyzing protein-protein
      interactions in high protein concentration solutions: correlation with static and
      dynamic light scattering measurements.
AB  - The purpose of this work was to establish ultrasonic storage modulus (G') as a
      novel parameter for characterizing protein-protein interactions (PPI) in high
      concentration protein solutions. Using an indigenously developed ultrasonic shear
      rheometer, G' for 20-120 mg/ml solutions of a monoclonal antibody (IgG(2)),
      between pH 3.0 and 9.0 at 4 mM ionic strength, was measured at frequency of 10
      MHz. Our understanding of ultrasonic rheology indicated decrease in repulsive and
      increase in attractive PPI with increasing solution pH. To confirm this behavior,
      dynamic (DLS) and static (SLS) light scattering measurements were conducted in
      dilute solutions. Due to technical limitations, light scattering measurements
      could not be conducted in concentrated solutions. Mutual-diffusion coefficient,
      measured by DLS, increased with IgG(2) concentration at pH 4.0 and this trend
      reversed as pH was increased to 9.0. Second virial coefficient, measured by SLS,
      decreased with increasing pH. These observations were consistent with the nature
      of PPI understood from G' measurements. Ultrasonic rheology, DLS, and SLS
      measurements were also conducted under conditions of increased ionic strength.
      The consistency between rheology and light scattering analysis under various
      solution conditions established the utility of ultrasonic G' measurements as a
      novel tool for analyzing PPI in high protein concentration systems.

PMID- 17028131
TI  - Time-dependent DNA condensation induced by amyloid beta-peptide.
AB  - The major protein component of the amyloid deposition in Alzheimer's disease is a
      39-43 residue peptide, amyloid beta (Abeta). Abeta is toxic to neurons, although
      the mechanism of neurodegeneration is uncertain. Evidence exists for non-B DNA
      conformation in the hippocampus of Alzheimer's disease brains, and Abeta was
      reportedly able to transform DNA conformation in vitro. In this study, we found
      that DNA conformation was altered in the presence of Abeta, and Abeta induced DNA
      condensation in a time-dependent manner. Furthermore, Abeta sheets, serving as
      condensation nuclei, were crucial for DNA condensation, and Cu(2+) and Zn(2+)
      ions inhibited Abeta sheet-induced DNA condensation. Our results suggest DNA
      condensation as a mechanism of Abeta toxicity.

PMID- 17028130
TI  - Protein crystallography under xenon and nitrous oxide pressure: comparison with
      in vivo pharmacology studies and implications for the mechanism of inhaled
      anesthetic action.
AB  - In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe)
      and nitrous oxide (N(2)O) act by blocking the N-methyl-d-aspartate (NMDA)
      receptor. Using x-ray crystallography, we examined the binding characteristics of
      these two gases on two soluble proteins as structural models: urate oxidase,
      which is a prototype of a variety of intracellular globular proteins, and annexin
      V, which has structural and functional characteristics that allow it to be
      considered as a prototype for the NMDA receptor. The structure of these proteins
      complexed with Xe and N(2)O were determined. One N(2)O molecule or one Xe atom
      binds to the same main site in both proteins. A second subsite is observed for
      N(2)O in each case. The gas-binding sites are always hydrophobic flexible
      cavities buried within the monomer. Comparison of the effects of Xe and N(2)O on
      urate oxidase and annexin V reveals an interesting relationship with the in vivo
      pharmacological effects of these gases, the ratio of the gas-binding sites'
      volume expansion and the ratio of the narcotic potency being similar. Given these
      data, we propose that alterations of cytosolic globular protein functions by
      general anesthetics would be responsible for the early stages of anesthesia such
      as amnesia and hypnosis and that additional alterations of ion-channel membrane
      receptor functions are required for deeper effects that progress to "surgical"
      anesthesia.

PMID- 17028132
TI  - Mechanism of the difference in the binding affinity of E. coli tRNAGln to
      glutaminyl-tRNA synthetase caused by noninterface nucleotides in variable loop.
AB  - Aminoacyl-tRNA synthetases (ARSs) distinguish their cognate tRNAs from many other
      kinds of tRNAs, despite the very similar tertiary structures of tRNAs. Many
      researchers have supported the view that this recognition is achieved by
      intermolecular interactions between tRNA and ARS. However, one of the aptamers of
      Escherichia coli glutamine specific tRNA, var-AGGU, has a higher affinity to ARS
      than the wild-type, although the sequence difference only lies in the variable
      loop located on the opposite side of the binding interface with ARS. To
      understand the reason for the difference in affinity, we did molecular dynamics
      simulations on tRNAs and their complexes with ARS. We calculated the enthalpic
      and entropic contributions to the binding free energy with the molecular
      mechanics-Poisson-Boltzmann/surface area method and found that the entropic
      difference plays an important role in the difference in binding free energies.
      During the molecular dynamics simulations, dynamic rearrangements of hydrogen
      bonds occurred in the tertiary core region of the wild-type tRNA, whereas they
      were not observed in the free var-AGGU simulation. Since the internal mobility
      was suppressed upon complex formation with ARS, the entropy loss in the wild-type
      was larger than that of the aptamer. We therefore concluded that the sequence
      difference in the variable loop caused the difference in the internal mobility of
      the tertiary core region tRNAs and led to the difference in the affinity to ARS
      through the entropy term.

PMID- 17028133
TI  - Growth dynamics of domains in ternary fluid vesicles.
AB  - We have studied the growth dynamics of domains on ternary fluid vesicles composed
      of saturated (dipalmitoylphosphatidylcholine), unsaturated
      (dioleoylphosphatidylcholine) phosphatidylcholine lipids, and cholesterol using a
      fluorescence microscopy. The domain coarsening processes are classified into two
      types: normal coarsening and trapped coarsening. For the normal coarsening, the
      domains having flat circular shape grow in a diffusion-and-coalescence manner and
      phenomenologically the mean size grows as a power law of approximately t(2/3).
      The observed growth law is not described by a two-dimensional diffusion-and
      coalescence growth mechanism following the Saffman and Delbruck theory, which may
      originate from the two-body hydrodynamic interactions between domains. For
      trapped coarsening, on the other hand, the domain coarsening is suppressed at a
      certain domain size because the repulsive interdomain interactions obstruct the
      coalescence of domains. The two-color imaging of the trapped domains reveals that
      the repulsive interactions are induced by the budding of domains. The model free
      energy consisting of the bending energy of domains, the bending energy of matrix,
      the line energy of domain boundary, and the translation energy of domains can
      describe the observed trapped coarsening. The trapping of domains is caused by
      the coupling between the phase separation and the membrane elasticity under the
      incompressibility constraint.

PMID- 17028134
TI  - Microtubule protofilament number is modulated in a stepwise fashion by the charge
      density of an enveloping layer.
AB  - Microtubules are able to adjust their protofilament (PF) number and, as a
      consequence, their dynamics and function, to the assembly conditions and presence
      of cofactors. However, the principle behind such variations is poorly understood.
      Using synchrotron x-ray scattering and transmission electron microscopy, we
      studied how charged membranes, which under certain conditions can envelop pre
      assembled MTs, regulate the PF number of those MTs. We show that the mean PF
      number, <N>, is modulated primarily by the charge density of the membranes. <N>
      decreases in a stepwise fashion with increasing membrane charge density. <N> does
      not depend on the membrane-protein stoichiometry or the solution ionic strength.
      We studied the effect of taxol and found that <N> increases logarithmically with
      taxol/tubulin stoichiometry. We present a theoretical model, which by balancing
      the electrostatic and elastic interactions in the system accounts for the trends
      in our findings and reveals an effective MT bending stiffness of order 10-100
      k(B)T/nm, associated with the observed changes in PF number.

PMID- 17028135
TI  - Collagen fibrils: nanoscale ropes.
AB  - The formation of collagen fibrils from staggered repeats of individual molecules
      has become "accepted" wisdom. However, for over thirty years now, such a model
      has failed to resolve several structural and functional questions. In a novel
      approach, it was found, using atomic force microscopy, that tendon collagen
      fibrils are composed of subcomponents in a spiral disposition-that is, their
      structure is similar to that of macroscale ropes. Consequently, this arrangement
      was modeled and confirmed using elastic rod theory. This work provides new
      insight into collagen fibril structure and will have wide application-from the
      design of scaffolds for tissue engineering and a better understanding of
      pathogenesis of diseases of bone and tendon, to the conservation of irreplaceable
      parchment-based museum exhibits.

PMID- 17028136
TI  - Possible pathway for ubiquinone shuttling in Rhodospirillum rubrum revealed by
      molecular dynamics simulation.
AB  - In the last decade, the structures of many components of the photosynthetic
      apparatus of purple bacteria, as well as the mutual organization of these
      components within the purple membrane, were resolved. One key question that
      emerged concerned the assembly of the core complex consisting of the reaction
      center (RC) and the light-harvesting 1 (LH1) complex. In some species, like
      Rhodobacter sphaeroides, the ring-shaped LH1 complex was found to be open,
      whereas other species, like Rhodospirillum rubrum, have a closed ring surrounding
      the reaction center. This poses the question of how the ubiquinone molecule that
      transports electrons and protons from the RC to the cytochrome bc(1) complex
      overcomes the apparent barrier of the LH1 ring. In this study, we investigated
      how, in the case of a closed LH1 ring, the ubiquinone molecule diffuses through
      the LH1 ring. For this purpose, the LH1 structure of R. rubrum was modeled and
      the potential of mean force along the diffusion pathway through the LH1 was
      determined by steered molecular-dynamics simulations. The potential was
      reconstructed using the fluctuation theorem in combination with the stiff spring
      approximation. An upper limit for the mean first-passage time for diffusion of
      ubiquinone through the LH1 ring, based on a worst-case scenario potential, was
      calculated as approximately 8 x 10(-3) s, which is still in agreement with known
      turnover rates of RC and RC-LH1 complexes in the range of approximately 1000 Hz.

PMID- 17028137
TI  - A structural origin of latency relaxation in frog skeletal muscle.
AB  - A time-resolved x-ray diffraction study at a time resolution of 0.53 ms was made
      to investigate the structural origin of latency relaxation (LR) in frog skeletal
      muscle. Intensity and spacing measurements were made on meridional reflections
      from the Ca-binding protein troponin and the thick filament and on layer lines
      from the thin filament. At 16 degrees C, the intensity and spacing of all
      reflections started to change at 4 ms, simultaneously with the LR. At 0 degrees
      C, the intensity of the troponin reflection and the layer lines from the thin
      filament and the spacing of the 14.3-nm myosin meridional reflection, but not the
      spacing of other myosin meridional reflections, began to change at approximately
      15 ms, when the LR also started. Intensity of myosin-based reflections started to
      change later. When the muscle was stretched to non-overlap length, the intensity
      and spacing changes of the myosin reflections disappeared. The simultaneous
      spacing change of the 14.3-nm myosin meridional reflection with the LR suggests
      that detachment of myosin heads that are bound to actin in the resting muscle is
      the cause of the LR.

PMID- 17028138
TI  - Cholesterol sulfate and Ca(2+) modulate the mixing properties of lipids in
      stratum corneum model mixtures.
AB  - The influence of cholesterol sulfate (CS) and calcium on the phase behavior of
      lipid mixtures mimicking the stratum corneum (SC) lipids was examined using
      vibrational spectroscopy. Raman microspectrocopy showed that equimolar mixtures
      of ceramide, palmitic acid, and cholesterol underwent a phase transition in
      which, at low temperatures, lipids formed mainly a mosaic of microcrystalline
      phase-separated domains, and above 45 degrees C, a more fluid and disordered
      phase in which the three lipid species were more miscible. In the presence of
      Ca(2+), there was the formation of fatty acid-Ca(2+) complexes that led to
      domains stable on heating. Consequently, these lipid mixtures remained
      heterogeneous, and the fatty acid molecules were not extensively involved in the
      formation of the fluid lipid phase, which included mainly ceramide and
      cholesterol. However, the presence of CS displaced the association site of Ca(2+)
      ions and inhibited the formation of domains formed by the fatty acid molecules
      complexed with Ca(2+) ions. This work reveals that CS and Ca(2+) modulate the
      lipid mixing properties and the lipid order in SC lipid models. The balance in
      the equilibria involving Ca(2+), CS, and fatty acids is proposed to have an
      impact on the organization and the function of the epidermis.

PMID- 17028139
TI  - Dynamics of the nucleotide pocket of myosin measured by spin-labeled nucleotides.
AB  - We have used electron paramagnetic probes attached to the ribose of ATP (SL-ATP)
      to monitor conformational changes in the nucleotide pocket of myosin. Spectra for
      analogs bound to myosin in the absence of actin showed a high degree of
      immobilization, indicating a closed nucleotide pocket. In the Actin.Myosin.SL
      AMPPNP, Actin.Myosin.SL-ADP.BeF(3), and Actin.Myosin.SL-ADP.AlF(4) complexes,
      which mimic weakly binding states near the beginning of the power stroke, the
      nucleotide pocket remained closed. The spectra of the strongly bound
      Actin.Myosin.SL-ADP complex consisted of two components, one similar to the
      closed pocket and one with increased probe mobility, indicating a more open
      pocket, The temperature dependence of the spectra showed that the two
      conformations of the nucleotide pocket were in equilibrium, with the open
      conformation more favorable at higher temperatures. These results, which show
      that opening of the pocket occurs only in the strongly bound states, appear
      reasonable, as this would tend to keep ADP bound until the end of the power
      stroke. This conclusion also suggests that force is initially generated by a
      myosin with a closed nucleotide pocket.

PMID- 17028140
TI  - Role of pairwise interactions between M1 and M2 domains of the nicotinic receptor
      in channel gating.
AB  - The adult form of the nicotinic acetylcholine receptor (AChR) consists of five
      subunits (alpha(2)betaepsilondelta), each having four transmembrane domains (M1
      M4). The atomic model of the nicotinic acetylcholine receptor shows that the pore
      lining M2 domains make no extensive contacts with the rest of the transmembrane
      domains. However, there are several sites where close appositions between
      segments occur. It has been suggested that the pair alphaM1-F15' and alphaM2-L11'
      is one of the potential interactions between segments. To determine
      experimentally if these residues are interacting and to explore if this
      interhelical interaction is essential for channel gating, we combined mutagenesis
      with single-channel kinetic analysis. Mutations in alphaM1-F15' lead to profound
      changes in the opening rate and slighter changes in the closing rate. Channel
      gating is impaired as the volume of the residue increases. Rate-equilibrium
      linear free-energy relationship analysis reveals an approximately 70% open-state
      like environment for alphaM1-F15' at the transition state of the gating reaction,
      suggesting that it moves early during the gating process. Replacing the residue
      at alphaM1-15' by that at alphaM2-11' and vice versa profoundly alters gating,
      but the combination of the two mutations restores gating to near normal,
      indicating that alphaM1-F15' and alphaM2-L11' are interchangeable. Double-mutant
      cycle analysis shows that these residues are energetically coupled. Thus, the
      interaction between M1 and M2 plays a key role in channel gating.

PMID- 17028141
TI  - Composition effect on peptide interaction with lipids and bacteria: variants of
      C3a peptide CNY21.
AB  - The effect of peptide hydrophobicity and charge on peptide interaction with model
      lipid bilayers was investigated for the C3a-derived peptide CNY21 by fluorescence
      spectroscopy, circular dichroism, ellipsometry, z-potential, and photon
      correlation spectroscopy measurements. For both zwitterionic and anionic
      liposomes, the membrane-disruptive potency for CNY21 variants increased with
      increasing net positive charge and mean hydrophobicity and was completely lost on
      elimination of all peptide positive charges. Analogous effects of elimination of
      the peptide positive net charge in particular were found regarding bacteria
      killing for both Pseudomonas aeruginosa and Bacillus subtilis. The peptides,
      characterized by moderate helix content both in buffer and when attached to the
      liposomes, displayed high adsorption for the net positively charged peptide
      variants, whereas adsorption was non-measurable for the uncharged peptide. That
      electrostatically driven adsorption represents the main driving force for
      membrane disruption in lipid systems was also demonstrated by a drastic reduction
      in both liposome leakage and peptide adsorption with increasing ionic strength,
      and this salt inactivation can be partly avoided by increasing the peptide
      hydrophobicity. This increased electrolyte resistance translates also to a higher
      antibacterial effect for the hydrophobically modified variant at high salt
      concentration. Overall, our findings demonstrate the importance of the peptide
      adsorption and resulting peptide interfacial density for membrane-disruptive
      effects of these peptides.

PMID- 17028142
TI  - Mechanical unfolding of RNA: from hairpins to structures with internal
      multiloops.
AB  - Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using
      laser optical tweezer experiments have begun to reveal the features of the energy
      landscape that cannot be easily explored using conventional experiments. Upon
      application of constant force (f), RNA hairpins undergo cooperative transitions
      from folded to unfolded states whereas subdomains of ribozymes unravel one at a
      time. Here, we use a self-organized polymer model and Brownian dynamics
      simulations to probe mechanical unfolding at constant force and constant-loading
      rate of four RNA structures of varying complexity. For simple hairpins, such as
      P5GA, application of constant force or constant loading rate results in bistable
      cooperative transitions between folded and unfolded states without populating any
      intermediates. The transition state location (DeltaxFTS) changes dramatically as
      the loading rate is varied. At loading rates comparable to those used in laser
      optical tweezer experiments, the hairpin is plastic, with DeltaxFTS being midway
      between folded and unfolded states; whereas at high loading rates, DeltaxFTS
      moves close to the folded state, i.e., RNA is brittle. For the 29-nucleotide TAR
      RNA with the three-nucleotide bulge, unfolding occurs in a nearly two-state
      manner with an occasional pause in a high free energy metastable state. Forced
      unfolding of the 55 nucleotides of the Hepatitis IRES domain IIa, which has a
      distorted L-shaped structure, results in well-populated stable intermediates. The
      most stable force-stabilized intermediate represents straightening of the L
      shaped structure. For these structures, the unfolding pathways can be predicted
      using the contact map of the native structures. Unfolding of a RNA motif with
      internal multiloop, namely, the 109-nucleotide prohead RNA that is part of the 29
      DNA packaging motor, at constant value of rf occurs with three distinct rips that
      represent unraveling of the paired helices. The rips represent kinetic barriers
      to unfolding. Our work shows 1), the response of RNA to force is largely
      determined by the native structure; and 2), only by probing mechanical unfolding
      over a wide range of forces can the underlying energy landscape be fully
      explored.

PMID- 17028144
TI  - Protein phase diagrams II: nonideal behavior of biochemical reactions in the
      presence of osmolytes.
AB  - In the age of biochemical systems biology, proteomics, and high throughput
      methods, the thermodynamic quantification of cytoplasmatic reaction networks
      comes into reach of the current generation of scientists. What is needed to
      efficiently extract the relevant information from the raw data is a robust tool
      for evaluating the number and stoichiometry of all observed reactions while
      providing a good estimate of the thermodynamic parameters that determine the
      molecular behavior. The recently developed phase-diagram method, strictly
      speaking a graphical representation of linkage or Maxwell Relations, offers such
      capabilities. Here, we extend the phase diagram method to nonideal conditions.
      For the sake of simplicity, we choose as an example a reaction system involving
      the protein RNase A, its inhibitor CMP, the osmolyte urea, and water. We
      investigate this system as a function of the concentrations of inhibitor and
      osmolyte at different temperatures ranging from 280 K to 340 K. The most
      interesting finding is that the protein-inhibitor binding equilibrium depends
      strongly on the urea concentration--by orders-of-magnitude more than expected
      from urea-protein interaction alone. Moreover, the m-value of ligand binding is
      strongly concentration-dependent, which is highly unusual. It is concluded that
      the interaction between small molecules like urea and CMP can significantly
      contribute to cytoplasmic nonideality. Such a finding is highly significant
      because of its impact on renal tissue where high concentrations of cosolutes
      occur regularly.

PMID- 17028143
TI  - Novel lipid transfer property of two mitochondrial proteins that bridge the inner
      and outer membranes.
AB  - This study provides evidence of a novel function for mitochondrial creatine
      kinase (MtCK) and nucleoside diphosphate kinase (NDPK-D). Both are basic
      peripheral membrane proteins with symmetrical homo-oligomeric structure, which in
      the case of MtCK was already shown to allow crossbridging of lipid bilayers.
      Here, different lipid dilution assays clearly demonstrate that both kinases also
      facilitate lipid transfer from one bilayer to another. Lipid transfer occurs
      between liposomes mimicking the lipid composition of mitochondrial contact sites,
      containing 30 mol % cardiolipin, but transfer does not occur when cardiolipin is
      replaced by phosphatidylglycerol. Ubiquitous MtCK, but not NDPK-D, shows some
      specificity in the nature of the lipids transferred and it is not active with
      phosphatidylcholine alone. MtCK can undergo reversible oligomerization between
      dimeric and octameric forms, but only the octamer can bridge membranes and
      promote lipid transfer. Cytochrome c, another basic mitochondrial protein known
      to bind to anionic membranes but not crosslinking them, is also incapable of
      promoting lipid transfer. The lipid transfer process does not involve vesicle
      fusion or loss of the internal contents of the liposomes.

PMID- 17028145
TI  - Contour length and refolding rate of a small protein controlled by engineered
      disulfide bonds.
AB  - The introduction of disulfide bonds into proteins creates additional mechanical
      barriers and limits the unfolded contour length (i.e., the maximal extension)
      measured by single-molecule force spectroscopy. Here, we engineer single
      disulfide bonds into four different locations of the human cardiac titin module
      (I27) to control the contour length while keeping the distance to the transition
      state unchanged. This enables the study of several biologically important
      parameters. First, we are able to precisely determine the end-to-end length of
      the transition state before unfolding (53 Angstrom), which is longer than the end
      to-end length of the protein obtained from NMR spectroscopy (43 Angstrom).
      Second, the measured contour length per amino acid from five different methods
      (4.0 +/- 0.2 Angstrom) is longer than the end-to-end length obtained from the
      crystal structure (3.6 Angstrom). Our measurement of the contour length takes
      into account all the internal degrees of freedom of the polypeptide chain,
      whereas crystallography measures the end-to-end length within the "frozen"
      protein structure. Furthermore, the control of contour length and therefore the
      number of amino acids unraveled before reaching the disulfide bond (n)
      facilitates the test of the chain length dependence on the folding time (tau(F)).
      We find that both a power law scaling tau(F) lambda n(lambda) with lambda = 4.4,
      and an exponential scaling with n(0.6) fit the data range, in support of
      different protein-folding scenarios.

PMID- 17028146
TI  - Transport governs flow-enhanced cell tethering through L-selectin at threshold
      shear.
AB  - Flow-enhanced cell adhesion is a counterintuitive phenomenon that has been
      observed in several biological systems. Flow augments L-selectin-dependent
      adhesion by increasing the initial tethering of leukocytes to vascular surfaces
      and by strengthening their subsequent rolling interactions. Tethering or rolling
      might be influenced by physical factors that affect the formation or dissociation
      of selectin-ligand bonds. We recently demonstrated that flow enhanced rolling of
      L-selectin-bearing microspheres or neutrophils on P-selectin glycoprotein ligand
      1 by force decreased bond dissociation. Here, we show that flow augmented
      tethering of these microspheres or cells to P-selectin glycoprotein ligand-1 by
      three transport mechanisms that increased bond formation: sliding of the sphere
      bottom on the surface, Brownian motion, and molecular diffusion. These results
      elucidate the mechanisms for flow-enhanced tethering through L-selectin.

PMID- 17028147
TI  - Anesthesia, analgesia, and euphoria.

PMID- 17028148
TI  - Molecular interactions between the specialist herbivore Manduca sexta
      (Lepidoptera, Sphingidae) and its natural host Nicotiana attenuata. VII. Changes
      in the plant's proteome.
AB  - When Manduca sexta attacks Nicotiana attenuata, fatty acid-amino acid conjugates
      (FACs) in the larvae's oral secretions (OS) are introduced into feeding wounds.
      These FACs trigger a transcriptional response that is similar to the response
      induced by insect damage. Using two-dimensional gel electrophoresis, matrix
      assisted laser desorption ionization-time of flight, and liquid chromatography
      tandem mass spectrometry, we characterized the proteins in phenolic extracts and
      in a nuclear fraction of leaves elicited by larval attack, and/or in leaves
      wounded and treated with OS, FAC-free OS, and synthetic FACs. Phenolic extracts
      yielded approximately 600 protein spots, many of which were altered by
      elicitation, whereas nuclear protein fractions yielded approximately 100 spots,
      most of which were unchanged by elicitation. Reproducible elicitor-induced
      changes in 90 spots were characterized. In general, proteins that increased were
      involved in primary metabolism, defense, and transcriptional and translational
      regulation; those that decreased were involved in photosynthesis. Like the
      transcriptional defense responses, proteomic changes were strongly elicited by
      the FACs in OS. A semiquantitative reverse transcription-PCR approach based on
      peptide sequences was used to compare transcript and protein accumulation
      patterns for 17 candidate proteins. In six cases the patterns of elicited
      transcript accumulation were consistent with those of elicited protein
      accumulation. Functional analysis of one of the identified proteins involved in
      photosynthesis, RuBPCase activase, was accomplished by virus-induced gene
      silencing. Plants with decreased levels of RuBPCase activase protein had reduced
      photosynthetic rates and RuBPCase activity, and less biomass, responses
      consistent with those of herbivore-attacked plants. We conclude that the response
      of the plant's proteome to herbivore elicitation is complex, and integrated
      transcriptome-proteome-metabolome analysis is required to fully understand this
      ubiquitous ecological interaction.

PMID- 17028149
TI  - Proteomic analysis of seed dormancy in Arabidopsis.
AB  - The mechanisms controlling seed dormancy in Arabidopsis (Arabidopsis thaliana)
      have been characterized by proteomics using the dormant (D) accession Cvi
      originating from the Cape Verde Islands. Comparative studies carried out with
      freshly harvested dormant and after-ripened non-dormant (ND) seeds revealed a
      specific differential accumulation of 32 proteins. The data suggested that
      proteins associated with metabolic functions potentially involved in germination
      can accumulate during after-ripening in the dry state leading to dormancy
      release. Exogenous application of abscisic acid (ABA) to ND seeds strongly
      impeded their germination, which physiologically mimicked the behavior of D
      imbibed seeds. This application resulted in an alteration of the accumulation
      pattern of 71 proteins. There was a strong down-accumulation of a major part
      (90%) of these proteins, which were involved mainly in energetic and protein
      metabolisms. This feature suggested that exogenous ABA triggers proteolytic
      mechanisms in imbibed seeds. An analysis of de novo protein synthesis by two
      dimensional gel electrophoresis in the presence of [(35)S]-methionine disclosed
      that exogenous ABA does not impede protein biosynthesis during imbibition.
      Furthermore, imbibed D seeds proved competent for de novo protein synthesis,
      demonstrating that impediment of protein translation was not the cause of the
      observed block of seed germination. However, the two-dimensional protein profiles
      were markedly different from those obtained with the ND seeds imbibed in ABA.
      Altogether, the data showed that the mechanisms blocking germination of the ND
      seeds by ABA application are different from those preventing germination of the D
      seeds imbibed in basal medium.

PMID- 17028150
TI  - Physiological characterization of two genes for Na+ exclusion in durum wheat,
      Nax1 and Nax2.
AB  - Durum wheat (Triticum turgidum L. subsp. durum Desf.) Line 149 contains two novel
      major genes for excluding Na(+) from leaf blades, named Nax1 and Nax2. The genes
      were separated into families containing a single gene and near-isogenic
      homozygous lines were selected. Lines containing either Nax1 or Nax2 had lower
      rates of Na(+) transport from roots to shoots than their near-isogenic pairs due
      to lower rates of net loading of the xylem, not to lower rates of net uptake from
      the soil or higher rates of retranslocation in the phloem. Nax1 and Nax2 lines
      also had higher rates of K(+) transport from root to shoot, resulting in an
      enhanced discrimination of K(+) over Na(+). Lines containing Nax1 differed from
      those containing Nax2 by unloading Na(+) from the xylem as it entered the shoot
      so that Na(+) was retained in the base of the leaf, leading to a high sheath to
      blade ratio of Na(+) concentration. Gradients in tissue concentrations of Na(+)
      along the leaf suggested that Na(+) was continually removed from the xylem. The
      Nax2 line did not retain Na(+) in the base of the leaf, suggesting that it
      functioned only in the root. The Nax2 gene therefore has a similar function to
      Kna1 in bread wheat (Triticum aestivum).

PMID- 17028151
TI  - Modifications to the Arabidopsis defense proteome occur prior to significant
      transcriptional change in response to inoculation with Pseudomonas syringae.
AB  - Alterations in the proteome of Arabidopsis (Arabidopsis thaliana) leaves during
      responses to challenge by Pseudomonas syringae pv tomato DC3000 were analyzed
      using two-dimensional gel electrophoresis. Protein changes characteristic of the
      establishment of disease, basal resistance, and resistance-gene-mediated
      resistance were examined by comparing responses to DC3000, a hrp mutant, and
      DC3000 expressing avrRpm1, respectively. The abundance of each protein identified
      was compared with that of selected transcripts obtained from comparable GeneChip
      experiments. We report changes in three subcellular fractions: total soluble
      protein, chloroplast enriched, and mitochondria enriched over four time points
      (1.5-6 h after inoculation). In total, 73 differential spots representing 52
      unique proteins were successfully identified. Many of the changes in protein spot
      density occurred before significant transcriptional reprogramming was evident
      between treatments. The high proportion of proteins represented by more than one
      spot indicated that many of the changes to the proteome can be attributed to
      posttranscriptional modifications. Proteins found to show significant change
      after bacterial challenge are representative of two main functional groups:
      defense-related antioxidants and metabolic enzymes. Significant changes to
      photosystem II and to components of the mitochondrial permeability transition
      were also identified. Rapid communication between organelles and regulation of
      primary metabolism through redox-mediated signaling are supported by our data.

PMID- 17028152
TI  - Large-scale cis-element detection by analysis of correlated expression and
      sequence conservation between Arabidopsis and Brassica oleracea.
AB  - The rapidly increasing amount of plant genomic sequences allows for the detection
      of cis-elements through comparative methods. In addition, large-scale gene
      expression data for Arabidopsis (Arabidopsis thaliana) have recently become
      available. Coexpression and evolutionarily conserved sequences are criteria
      widely used to identify shared cis-regulatory elements. In our study, we employ
      an integrated approach to combine two sources of information, coexpression and
      sequence conservation. Best-candidate orthologous promoter sequences were
      identified by a bidirectional best blast hit strategy in genome survey sequences
      from Brassica oleracea. The analysis of 779 microarrays from 81 different
      experiments provided detailed expression information for Arabidopsis genes
      coexpressed in multiple tissues and under various conditions and developmental
      stages. We discovered candidate transcription factor binding sites in 64% of the
      Arabidopsis genes analyzed. Among them, we detected experimentally verified
      binding sites and showed strong enrichment of shared cis-elements within
      functionally related genes. This study demonstrates the value of partially
      shotgun sequenced genomes and their combinatorial use with functional genomics
      data to address complex questions in comparative genomics.

PMID- 17028153
TI  - Differential operation of dual protochlorophyllide reductases for chlorophyll
      biosynthesis in response to environmental oxygen levels in the cyanobacterium
      Leptolyngbya boryana.
AB  - Most oxygenic phototrophs, including cyanobacteria, have two structurally
      unrelated protochlorophyllide (Pchlide) reductases in the penultimate step of
      chlorophyll biosynthesis. One is light-dependent Pchlide reductase (LPOR) and the
      other is dark-operative Pchlide reductase (DPOR), a nitrogenase-like enzyme
      assumed to be sensitive to oxygen. Very few studies have been conducted on how
      oxygen-sensitive DPOR operates in oxygenic phototrophic cells. Here, we report
      that anaerobic conditions are required for DPOR to compensate for the loss of
      LPOR in cyanobacterial cells. An LPOR-lacking mutant of the cyanobacterium
      Leptolyngbya boryana (formerly Plectonema boryanum) failed to grow in high light
      conditions and this phenotype was overcome by cultivating it under anaerobic
      conditions (2% CO(2)/N(2)). The critical oxygen level enabling the mutant to grow
      in high light was determined to be 3% (v/v). Oxygen-sensitive Pchlide reduction
      activity was successfully detected as DPOR activity in cell-free extracts of
      anaerobically grown mutants, whereas activity was undetectable in the wild type.
      The content of two DPOR subunits, ChlL and ChlN, was significantly increased in
      mutant cells compared with wild type. This suggests that the increase in subunits
      stimulates the DPOR activity that is protected efficiently from oxygen by
      anaerobic environments, resulting in complementation of the loss of LPOR. These
      results provide important concepts for understanding how dual Pchlide reductases
      operate differentially in oxygenic photosynthetic cells grown under natural
      environments where oxygen levels undergo dynamic changes. The evolutionary
      implications of the coexistence of two Pchlide reductases are discussed.

PMID- 17028154
TI  - AKINbetagamma contributes to SnRK1 heterotrimeric complexes and interacts with
      two proteins implicated in plant pathogen resistance through its KIS/GBD
      sequence.
AB  - The sucrose nonfermenting-1 protein kinase (SNF1)/AMP-activated protein kinase
      subfamily plays a central role in metabolic responses to nutritional and
      environmental stresses. In yeast (Saccharomyces cerevisiae) and mammals, the beta
      and gamma-noncatalytic subunits are implicated in substrate specificity and
      subcellular localization, respectively, and regulation of the kinase activity.
      The atypical betagamma-subunit has been previously described in maize (Zea mays),
      presenting at its N-terminal end a sequence related to the KIS (kinase
      interacting sequence) domain specific to the beta-subunits (Lumbreras et al.,
      2001). The existence of two components, SNF1-related protein kinase (SnRK1)
      complexes containing the betagamma-subunit and one SnRK1 kinase, had been
      proposed. In this work, we show that, despite its unusual features, the
      Arabidopsis (Arabidopsis thaliana) homolog AKINbetagamma clearly interacts with
      AKINbeta-subunits in vitro and in vivo, suggesting its involvement in
      heterotrimeric complexes located in both cytoplasm and nucleus. Unexpectedly, a
      transcriptional analysis of AKINbetagamma gene expression highlighted the
      implication of alternative splicing mechanisms in the regulation of AKINbetagamma
      expression. A two-hybrid screen performed with AKINbetagamma as bait, together
      with in planta bimolecular fluorescence complementation experiments, suggests the
      existence of interactions in the cytosol between AKINbetagamma and two leucine
      rich repeats related to pathogen resistance proteins. Interestingly, this
      interaction occurs through the truncated KIS domain that corresponds exactly to a
      GBD (glycogen-binding domain) recently described in mammals and yeast. A
      phylogenetic study suggests that AKINbetagamma-related proteins are restricted to
      the plant kingdom. Altogether, these data suggest the existence of plant-specific
      SnRK1 trimeric complexes putatively involved in a plant-specific function such as
      plant-pathogen interactions.

PMID- 17028155
TI  - The BnALMT1 and BnALMT2 genes from rape encode aluminum-activated malate
      transporters that enhance the aluminum resistance of plant cells.
AB  - The release of organic anions from roots can protect plants from aluminum (Al)
      toxicity and help them overcome phosphorus (P) deficiency. Our previous findings
      showed that Al treatment induced malate and citrate efflux from rape (Brassica
      napus) roots, and that P deficiency did not induce the efflux. Since this
      response is similar to the malate efflux from wheat (Triticum aestivum) that is
      controlled by the TaALMT1 gene, we investigated whether homologs of TaALMT1 are
      present in rape and whether they are involved in the release of organic anions.
      We isolated two TaALMT1 homologs from rape designated BnALMT1 and BnALMT2 (B.
      napus Al-activated malate transporter). The expression of these genes was induced
      in roots, but not shoots, by Al treatment but P deficiency had no effect. Several
      other cations (lanthanum, ytterbium, and erbium) also increased BnALMT1 and
      BnALMT2 expression in the roots. The function of the BnALMT1 and BnALMT2 proteins
      was investigated by heterologous expression in cultured tobacco (Nicotiana
      tabacum) cells and in Xenopus laevis oocytes. Both transfection systems showed an
      enhanced capacity for malate efflux but not citrate efflux, when exposed to Al.
      Smaller malate fluxes were also activated by ytterbium and erbium treatment.
      Transgenic tobacco cells grew significantly better than control cells following
      an 18 h treatment with Al, indicating that the expression of BnALMT1 and BnALMT2
      increased the resistance of these plant cells to Al stress. This report
      demonstrates that homologs of the TaALMT1 gene from wheat perform similar
      functions in other species.

PMID- 17028156
TI  - Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein,
      blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression
      of NF-kappaB-regulated antiapoptotic and metastatic gene products.
AB  - Identifying the active chemical ingredients of ancient medicines and the
      molecular targets of those ingredients is an attractive therapeutic objective.
      Embelin, identified primarily from the Embelia ribes plant, is one such compound
      shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities
      through an unknown mechanism. Because nuclear factor-kappaB (NF-kappaB) regulates
      several genes associated with inflammation, proliferation, carcinogenesis, and
      apoptosis, we postulated that embelin might mediate its activity through
      modulation of NF-kappaB activation. We found that embelin inhibited tumor
      necrosis factor (TNF) alpha-induced NF-kappaB activation. Both inducible and
      constitutive NF-kappaB activation were abrogated by embelin. In addition, NF
      kappaB activated by diverse stimuli such as interleukin-1beta,
      lipopolysaccharide, phorbol myristate acetate, okadaic acid, hydrogen peroxide,
      and cigarette smoke condensate also was suppressed. We found that embelin
      inhibited sequentially the TNFalpha-induced activation of the inhibitory subunit
      of NF-kappaBalpha (IkappaBalpha) kinase, IkappaBalpha phosphorylation,
      IkappaBalpha degradation, and p65 phosphorylation and nuclear translocation.
      Embelin also suppressed NF-kappaB-dependent reporter gene transcription induced
      by TNFalpha, TNF receptor-1 (TNFR1), TNFR1-associated death domain protein, TNFR
      associated factor-2, NF-kappaB-inducing kinase, and IkappaBalpha kinase but not
      by p65. Furthermore, we found that embelin down-regulated gene products involved
      in cell survival, proliferation, invasion, and metastasis of the tumor. This down
      regulation was associated with enhanced apoptosis by cytokine and
      chemotherapeutic agents. Together, our results indicate that embelin is a novel
      NF-kappaB blocker and potential suppressor of tumorigenesis.

PMID- 17028157
TI  - The positional influence of the helical geometry of the heteroduplex substrate on
      human RNase H1 catalysis.
AB  - In a companion study published in this issue (p. 83), we showed that chimeric
      substrates containing 2'-methoxyethyl (MOE) nucleotides inhibited human RNase H1
      activity. In this study, we prepared chimeric substrates containing a central DNA
      region with flanking northern-biased MOE nucleotides hybridized to complementary
      RNA. Conformationally biased and flexible modified nucleotides were positioned at
      the junctions between the DNA and MOE residues of the chimeric substrates to
      modulate the effects of the MOE residues on human RNase H1 activity. The strong
      northern-biased locked-nucleic acid modification exacerbated the negative effects
      of the MOE modifications resulting in slower human RNase H1 cleavage rates.
      Enhanced cleavage rates were observed for the eastern-biased 2'-ara
      fluorothymidine and bulge inducing N-methylthymidine modifications positioned at
      the 5'-DNA/3'-MOE junction as well as the southern-biased 2'-methylthiothymidine
      and conformationally flexible tetrafluoroindole (TFI) modifications positioned at
      the 5'-MOE/3'-DNA junction. The heterocycle of the ribonucleotide opposing the
      TFI deoxyribonucleotide had no effect on the human RNase H1 activity, whereas
      nucleotide substitutions adjacent the TFI significantly affected the cleavage
      rate. Mismatch base pair(s) exhibited similar effects on human RNase H1 activity
      as the TFI modifications. The effects of the TFI modification and mismatch base
      pair(s) on human RNase H1 activity were influenced by the position of the
      modification relative to the nucleotides interacting with the catalytic site of
      the enzyme rather than the juxtaposition of the modification to the MOE residues.
      Finally, these results provide a method for enhancing the human RNase H1 activity
      of chimeric antisense oligonucleotides (ASO) as well as the design of more potent
      ASO drugs.

PMID- 17028158
TI  - Human RNase H1 discriminates between subtle variations in the structure of the
      heteroduplex substrate.
AB  - In a previous study, we demonstrated that the sugar conformation and helical
      geometry of the heteroduplex substrate at the catalytic site of human RNase H1
      directs the selective recognition of the substrate by the enzyme (J Biol Chem
      279: 36317-36326, 2004). In this study, we systematically introduced 2'
      methoxyethoxy (MOE) nucleotides into the antisense oligodeoxyribonucleotide (ASO)
      of the heteroduplex to alter the helical geometry of the substrate. The MOE
      substitutions at the 3' and 5' poles of the ASO resulted in fewer cleavage sites
      and slower cleavage rates compared with the unmodified substrates. Furthermore, a
      greater reduction in cleavage activity was observed for MOE substitutions at the
      5' pole of the ASO. The 3'- and 5'-most cleavage sites were positioned two and
      four to five base pairs, respectively, from the nearest MOE residues, suggesting
      a conformational transmission of the MOE/RNA helical geometry into the DNA/RNA
      portion of the heteroduplex. Similar conformational transmission was observed for
      Okazaki-like substrates containing deoxyribonucleotide substitutions at the 3'
      pole of the oligoribonucleotide. Finally, the heteroduplex substrates exhibited
      preferred cleavage sites that were cleaved 2- to 3-fold faster than other sites
      in the substrate, and these sites exhibited the greatest influence on the initial
      cleavage rates. The data presented here offer further insights into the role
      substrate structure plays in directing human RNase H1 activity as well as the
      design of effective ASOs.

PMID- 17028159
TI  - The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and
      xenobiotic nuclear receptor.
AB  - Sulforaphane (SFN) is a biologically active phytochemical found abundantly in
      broccoli. SFN has been promoted as a putative chemopreventive agent to reduce
      cancer, and most studies have associated its anti-cancer effects with the
      induction of phase II xenobiotic metabolism enzymes via activation of the
      Keap1/Nrf2 antioxidant response pathway. Interestingly, SFN can significantly
      down-regulate cytochrome P450 3A4 (CYP3A4) expression in human primary
      hepatocytes. CYP3A4 is responsible for the hepatic and intestinal metabolism of
      numerous protoxicants, pharmaceutical compounds, and endogenous sterols. Among
      the most important mediators of CYP3A4 expression is the nuclear hormone
      receptor, steroid and xenobiotic receptor (SXR; also called "hPXR"). SXR
      functions as a xenobiotic sensor to coordinately regulate xenobiotic metabolism
      via transcriptional regulation of xenobiotic-detoxifying enzymes and
      transporters. Here, we report that SFN is a specific antagonist of human SXR and
      that it inhibits SXR-mediated induction of drug clearance. SFN can bind directly
      to SXR, inhibit SXR coactivator recruitment, and efficiently repress SXR
      activities. Furthermore, SFN inhibited SXR-mediated CYP3A4 expression and CYP3A4
      catalyzed midazolam clearance in human primary hepatocytes. Thus, SFN is the
      first identified naturally occurring antagonist for SXR (hPXR). Because induction
      of CYP3A4 can result in adverse drug responses (e.g., lack of efficacy), which
      are a major public health problem, this discovery could lead to the development
      of important new therapeutic and dietary approaches to reduce the frequency of
      undesirable inducer-drug interactions.

PMID- 17028160
TI  - O2 delivery and redox state are determinants of compartment-specific reactive O2
      species in myocardial reperfusion.
AB  - Reperfusion of the ischemic myocardium leads to a burst of reactive O(2) species
      (ROS), which is a primary determinant of postischemic myocardial dysfunction. We
      tested the hypothesis that early O(2) delivery and the cellular redox state
      modulate the initial myocardial ROS production at reperfusion. Isolated buffer
      perfused rat hearts were loaded with the fluorophores dihydrofluorescein or
      Amplex red to detect intracellular and extracellular ROS formation using surface
      fluorometry at the left ventricular wall. Hearts were made globally ischemic for
      20 min and then reperfused with either 95% or 20% O(2)-saturated perfusate. The
      same protocol was repeated in hearts loaded with dihydrofluorescein and perfused
      with either 20 or 5 mM glucose-buffered solution to determine relative changes in
      NADH and FAD. Myocardial O(2) delivery during the first 5 min of reperfusion was
      84.7 +/- 4.2 ml O(2)/min with 20% O(2)-saturated buffer and 354.4 +/- 22.8 ml
      O(2)/min with 95% O(2) (n = 8/group, P < 0.001). The fluorescein signal
      (intracellular ROS) was significantly increased in hearts reperfused with 95%
      O(2) compared with 20% O(2). However, the resorufin signal (extracellular ROS)
      was significantly increased with 20% O(2) compared with 95% O(2) during
      reperfusion. Perfusion of hearts with 20 mM glucose reduced the (.)NADH during
      ischemia (P < 0.001) and the (.)ROS at reperfusion (P < 0.001) compared with 5.5
      mM-perfused glucose hearts. In conclusion, initial O(2) delivery to the ischemic
      myocardium modulates a compartment-specific ROS response at reperfusion such that
      high O(2) delivery promotes intracellular ROS and low O(2) delivery promotes
      extracellular ROS. The redox state that develops during ischemia appears to be an
      important precursor for reperfusion ROS production.

PMID- 17028161
TI  - Validation of the wall motion score and myocardial performance indexes as novel
      techniques to assess cardiac function in mice after myocardial infarction.
AB  - The aim of this study was to determine the feasibility and accuracy of wall
      motion score index (WMSI) and myocardial performance index (MPI) for measuring
      regional and global left ventricular (LV) function with use of high-resolution
      echocardiography after myocardial infarction (MI) in mice. In 48 mice, myocardial
      infarction was induced by ligation in the middle of the left anterior descending
      coronary artery. Echocardiography was performed under anesthesia at baseline and
      1 mo after MI. WMSI was analyzed by a 16-segment model on short-axis views, and
      wall motion was scored as 1 for normal, 2 for hypokinetic, 3 for akinetic, 4 for
      dyskinetic, and 5 for aneurysmal. WMSI was calculated as the sum of scores
      divided by the total number of segments. MPI was calculated on the basis of
      isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT), and
      ejection time (ET): MPI = (IVCT + IVRT)/ET. We measured LV ejection fraction
      (LVEF), end-systolic and end-diastolic volumes (ESV and EDV), fractional
      shortening (FS), and infarct size (IS). LVEF at 4 wk after MI was reduced at 32.8
      +/- 9.0%. Linear correlation analyses showed that WMSI (1.6 +/- 0.3) correlated
      with LVEF (r = -0.84, P < 0.0005), FS (r = -0.43, P = 0.003), and IS (34.3 +/-
      15.3%, r = 0.86, P < 0.0005). MPI (0.67 +/- 0.09) correlated with LVEF (r = 
      0.67, P < 0.0005) and IS (r = 0.72, P < 0.0005). MPI also correlated with mitral
      inflow velocity (r = -0.68, P < 0.0005) and deceleration time (r = -0.42, P =
      0.003). Stepwise regression analysis revealed that WMSI was independently
      associated with IS. IS, FS, mitral inflow velocity, and deceleration time were
      independent determinants of MPI. In conclusion, echocardiographic assessments of
      WMSI and MPI in mice are feasible and correlate strongly with two-dimensional
      measurement of LV function and IS. These novel parameters provide additional
      noninvasive assessment of regional and global LV function in mice after MI.

PMID- 17028162
TI  - Characterization and localization of Ac-SDKP receptor binding sites using 125I
      labeled Hpp-Aca-SDKP in rat cardiac fibroblasts.
AB  - We have shown that the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac
      SDKP) inhibited endothelin-1 (ET-1)-induced cell proliferation and collagen
      synthesis in cultured rat cardiac fibroblasts (CFs) and reduced left ventricle
      collagen deposition in rats with aldosterone (salt)- and ANG II-induced
      hypertension. However, it is not known whether these effects are mediated by
      receptor binding sites specific for Ac-SDKP. We hypothesized that Ac-SDKP exerts
      antifibrotic effects by binding to specific receptor sites in cultured rat CFs,
      which mediate the inhibitory effects of Ac-SDKP on ET-1-stimulated collagen
      synthesis. Ac-SDKP binding sites in rat CFs and hearts were characterized by a
      specific radioligand, (125)I-labeled 3-(p-hydroxyphenyl)-propionic acid (or
      desaminotyrosine) (Hpp)-Aca-SDKP, a biologically active analog of Ac-SDKP. (125)I
      labeled Hpp-Aca-SDKP bound to rat CFs and fractionated membranes with similar
      affinities and specificity in a concentration- and time-dependent fashion.
      Scatchard plot analyses revealed a single class of high-affinity Hpp-Aca-SDKP
      binding sites (maximal binding: 1,704 +/- 198 fmol/mg protein; dissociation
      constant: 3.3 +/- 0.6 nM). (125)I-labeled Hpp-Aca-SDKP binding in CFs was
      displaced by unlabeled native peptide Ac-SDKP (inhibition constant: 0.69 +/- 0.15
      nM) and the analog Hpp-Aca-SDKP (inhibition constant: 10.4 +/- 0.2 nM) but not
      the unrelated peptide ANG II or ET-1 (10 microM). In vitro, both Ac-SDKP and Hpp
      Aca-SDKP inhibited ET-1-stimulated collagen synthesis in CFs in a dose-dependent
      fashion, reaching a maximal effect at 1 nM (control: 7.5 +/- 0.4, ET-1: 19.9 +/-
      1.2, ET-1+SDKP: 7.7 +/- 0.4, ET-1+Hpp-Aca-SDKP: 9.7 +/- 0.1 microg/mg protein; P
      < 0.001). Ac-SDKP also significantly attenuated ET-1-induced increases in
      intracellular calcium and MAPK ERK1/2 phosphorylation in CFs. In the rat heart,
      in vitro autoradiography revealed specific (125)I-labeled Hpp-Aca-SDKP binding
      throughout the myocardium, primarily interstitially. We believe that these
      results demonstrate for the first time that Hpp-Aca-SDKP is a functional ligand
      specific for Ac-SDKP receptor binding sites and that both Ac-SDKP and Hpp-Aca
      SDKP exert antifibrotic effects by binding to Ac-SDKP receptors in rat CFs.

PMID- 17028163
TI  - TNF-alpha potentiates protein-tyrosine nitration through activation of NADPH
      oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic
      endothelial cells.
AB  - A major source of reactive oxygen species (ROS) in endothelial cells is the NADPH
      oxidase enzyme complex. The selective distributions of any enzyme within cells
      have important implications in regulating enzyme effectiveness through
      facilitation of access to local substrates and/or product targets. Because
      membrane rafts provide a spatially preferable environment for a variety of enzyme
      systems, we sought to determine whether NADPH oxidase is present and functional
      in this plasma membrane compartment in endothelial cells. We found that, in
      resting endothelial cells, NADPH oxidase subunits were preassembled and the
      enzyme functional in membrane rafts, specifically in caveolae. Stimulation with
      TNF-alpha induced additional recruitment of the p47(phox) regulatory subunit to
      raft-localized NADPH oxidase and enhanced ROS production within raft domains. TNF
      alpha also induced nitric oxide production through activation of endothelial
      nitric oxide synthase (eNOS) present in the same membrane compartment. The dual
      activation of superoxide and nitric oxide-generating systems provided a spatially
      favorable environment for nitration of tyrosine-containing proteins localized to
      rafts. Perturbation of membrane raft structural integrity with cholesterol
      sequestering compounds caused the delocalization of NADPH oxidase subunits and
      eNOS from the rafts and inhibited TNF-alpha-induced ROS production and protein
      tyrosine nitration. Together, these data provide evidence that membrane rafts and
      caveolae play a role in the spatial regulation of NADPH oxidase and subsequent
      ROS/reactive nitrogen species in endothelial cells.

PMID- 17028164
TI  - ANG II type 1A receptor signaling causes unfavorable scar dynamics in the
      postinfarct heart.
AB  - Blockade of ANG II type 1A receptor (AT(1A)) is known to attenuate postinfarction
      [postmyocardial infarction (post-MI)] heart failure, accompanying reduction in
      fibrosis of the noninfarcted area. In the present study, we investigated the
      influence of AT(1A) blockade on the infarcted tissue itself. Consistent with
      earlier reports, AT(1A) knockout (AT(1A)KO) mice showed significantly attenuated
      left ventricular (LV) remodeling (dilatation) and dysfunction compared with wild
      type (WT) mice. Morphometry revealed that the infarcted wall was thicker and had
      a smaller circumferential length in AT(1A)KO than WT hearts. In addition,
      significantly greater numbers of cells were present within infarcts in AT(1A)KO
      hearts 4 wk post-MI; most notably, there was an abundance of vessels and
      myofibroblasts. One week post-MI, the incidence of apoptosis among granulation
      tissue cells was fewer (3.3 +/- 0.4 vs. 4.4 +/- 0.5% in WT, P < 0.05), whereas
      vessel proliferation was higher in AT(1A)KO hearts, which likely explains the
      later abundance of cells within the scar tissue. Insulin-like growth factor
      receptor-I was upregulated and its downstream signal protein kinase B (Akt) was
      significantly activated in infarcted AT(1A)KO hearts compared with WT hearts.
      Inactivation of Akt with wortmannin partially but significantly prevented the
      benefits observed in AT(1A)KO. Collectively, in AT(1A)KO hearts, Akt-mediated
      granulation tissue cell proliferation and preservation resulting from
      antiapoptosis likely contributed to an abundant cell population that altered the
      infarct scar structure, thereby reducing wall stress and attenuating LV
      dilatation and dysfunction at the chronic stage. In conclusion, altered
      structural dynamics of infarct scar and increasing myocardial fibrosis may be
      responsible for the deleterious effects of AT(1A) signaling following MI.

PMID- 17028165
TI  - Long-term room temperature storage of high-quality embryonic stem cell genomic
      DNA extracted with a simple and rapid procedure.
AB  - A very simple procedure for the isolation of high-quality, high-molecular-weight
      genomic DNA from embryonic stem cells is described. The DNA is very stable once
      dried and can be stored for long periods of time without refrigeration. Living
      cells are lysed in a sodium dodecyl sulfate and EDTA buffer containing proteinase
      K and then air-dried. Samples can be processed in bulk, and an individual can
      easily process thousands of samples for extraction and shipment on a daily basis
      using only common laboratory materials such as plastic ware and a multichannel
      pipetteman.

PMID- 17028166
TI  - Biological systems modeling and analysis: a biomolecular technique of the twenty
      first century.
AB  - It is proposed that computational systems biology should be considered a
      biomolecular technique of the twenty-first century, because it complements
      experimental biology and bioinformatics in unique ways that will eventually lead
      to insights and a depth of understanding not achievable without systems
      approaches. This article begins with a summary of traditional and novel modeling
      techniques. In the second part, it proposes concept map modeling as a useful link
      between experimental biology and biological systems modeling and analysis.
      Concept map modeling requires the collaboration between biologist and modeler.
      The biologist designs a regulated connectivity diagram of processes comprising a
      biological system and also provides semi-quantitative information on stimuli and
      measured or expected responses of the system. The modeler converts this
      information through methods of forward and inverse modeling into a mathematical
      construct that can be used for simulations and to generate and test new
      hypotheses. The biologist and the modeler collaboratively interpret the results
      and devise improved concept maps. The third part of the article describes
      software, BST-Box, supporting the various modeling activities.

PMID- 17028167
TI  - In vitro optimization of antisense oligodeoxynucleotide design: an example using
      the connexin gene family.
AB  - The completion of the human and mouse genomes has identified at least 20 connexin
      isomers in this family of intercellular channel proteins. However, there are no
      specific gap junction blockers or channel-blocking mimetic peptides available for
      the study of specific connexins. We designed antisense oligodeoxynucleotides that
      functionally reduce targeted connexin protein expression and can be used to
      reveal the biological function of individual connexins in vivo. Connexin mRNA was
      firstly exposed in vitro to deoxyribozymes complementing the sense coding
      sequence. Those that cleaved the target connexin mRNA in defined regions were
      used as the basis to design oligodeoxynucleotides to the accessible sites, thus
      taking into account tertiary mRNA configurations rather than relying on computed
      predictions. Antisense oligodeoxynucleotides designed to bind to accessible mRNA
      sites selectively reduced connexin26 and -43 mRNA expression in a corneal
      epithelium ex vivo model. Connexin43 protein levels were reduced correlating with
      the knockdown in mRNA and the protein's rapid turnover; protein levels of
      connexin26 did not alter, supporting lower turnover rates reported for that
      protein. We show, for the first time, an inexpensive and empirical approach to
      the preparation of specific and functional antisense oligodeoxynucleotides
      against known gene targets in the post-genomic era.

PMID- 17028168
TI  - Optimization of the Tet-On system for inducible expression of RAGE.
AB  - We have optimized a two-plasmid Tet-On system, the regulatory plasmid and the
      response plasmid, to produce tightly controlled inducible expression of the gene
      RAGE in cell-culture models. Two sets of plasmids were constructed: set 1
      (universal; for broad range of cell types) and set 2 (neuron specific). For the
      response plasmid, the gene RAGE was cloned in pIRES2-EGFP plasmid (Clontech) and
      the CMV promoter replaced with TREtight (modified seven copies of Tet-operon
      fused with CMVm promoter). For the regulatory plasmid, rtTA (reverse tetracycline
      transactivator) was placed under either the CMV promoter or the cell-specific
      promoter neuronal specific enolase. Both plasmids have the mammalian selection
      marker neomycine; the EGFP reporter gene is only in the response plasmid and IRES
      is between the gene and EGFP. Following induction with doxycycline, cells
      expressing RAGE showed neomycine resistance and green fluorescence (EGFP). Our
      system has been tested in two different cell lines and showed negligible basal
      leakiness, high induction of the gene RAGE (142-fold), dose-dependent response to
      doxycycline, and strict cell-type specificity. This system is highly suitable for
      cell-specific expression of any gene of interest in primary cultures and mixed
      cell populations.

PMID- 17028169
TI  - Critical role for the beta regulatory subunits of Cav channels in T lymphocyte
      function.
AB  - Calcium ion is a universal signaling intermediate, which is known to control
      various biological processes. In excitable cells, voltage-gated calcium channels
      (Cav) are the major route of calcium entry and regulate multiple functions such
      as contraction, neurotransmitter release, and gene transcription. Here we show
      that T lymphocytes, which are nonexcitable cells, express both regulatory beta
      and pore-forming Cav1 alpha1 subunits of Cav channels, and we provide genetic
      evidence for a critical role of the Cav beta3 and Cav beta4 regulatory subunits
      in T lymphocyte function. Cav beta-deficient T lymphocytes fail to acquire normal
      functions, and they display impairment in the T cell receptor-mediated calcium
      response, nuclear factor of activated T cells activation, and cytokine
      production. In addition, unlike in excitable cells, our data suggest a minimal
      physiological role for depolarization in Cav channel opening in T cells. T cell
      receptor stimulation induces only a small depolarization of T cells, and
      artificial depolarization of T cells using KCl does not lead to calcium entry.
      These observations suggest that the Cav channels expressed by T cells have
      adopted novel regulation/gating mechanisms.

PMID- 17028170
TI  - Suppression of hypoxia-induced HIF-1alpha and of angiogenesis in endothelial
      cells by myo-inositol trispyrophosphate-treated erythrocytes.
AB  - Allosteric regulation of oxygen delivery by RBCs may have significant effects on
      tumor growth. Indeed, angiogenesis, the formation of new blood vessels, is
      induced in growing tumors by low oxygen partial pressure. Hypoxia-inducible genes
      are switched on, among which are the VEGF gene and its receptors. Most important,
      under hypoxia, hypoxia-inducible factor 1alpha has a significantly prolonged half
      life and up-regulates a number of hypoxia genes. Human microvascular endothelial
      cells (MECs), when subjected in vitro to hypoxia, align to form vessel-like
      structures as in the angiogenic process. We report here that, when cultured in
      hypoxic conditions in the presence of human RBCs loaded with a new membrane
      permeant allosteric effector of Hb, myo-inositol trispyrophosphate (ITPP),
      endothelial cells (ECs) do not align, i.e., do not form "vessel"-like structures,
      because the "loaded" RBCs are capable of releasing under hypoxia more oxygen than
      their "normal" counterparts. Levels of VEGF and of hypoxia-inducible factor
      1alpha, elevated in the human MECs under hypoxia, were dramatically reduced or
      even suppressed in the presence of the ITPP-loaded RBCs. Treatment of these ECs
      directly with free ITPP at different concentrations had no effect on their
      ability to undertake angiogenesis. Incubation with ITPP enhances the capacity of
      Hb to release bound oxygen, leading to higher oxygen tension in the hypoxic
      environment, thus inhibiting hypoxia-induced angiogenesis. These observations are
      suggestive of a potential in vivo role of ITPP-loaded, "low-O2-affinity" RBCs in
      cancer therapy.

PMID- 17028171
TI  - miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar
      stimulation, inhibits Fos translation.
AB  - The transcription factor activator protein 1 (AP-1) is formed through the
      dimerization of immediate-early genes Fos and Jun family members. Activator
      protein 1 is known as a pivotal regulator of major biological events such as cell
      proliferation, differentiation, organogenesis, memory formation, and apoptosis.
      During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that
      repress gene expression of target mRNAs in animals posttranscriptionally) that
      are differentially expressed in the mouse paraventricular and supraoptic nuclei
      after 10 days of drinking 2% saline, one candidate microRNA that is relatively
      highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence
      analysis suggested a likely interaction with the 3' untranslated region of Fos
      mRNA. We show that miR-7b expression inhibits Fos translation in vitro and that
      it and its host gene are prominently expressed in the PVN and other brain areas,
      including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed.
      Normally, Fos is expressed at low to undetectable levels in cells, but it shows
      rapid induction and decay after acute stimuli. Various pathways have been
      identified through which Fos family proteins are degraded; our results indicate a
      significant additional mechanism by which Fos protein and activity may be
      regulated.

PMID- 17028172
TI  - Switching off calcium-dependent inactivation in L-type calcium channels by an
      autoinhibitory domain.
AB  - The retinal L-type Ca2+ channel Cav1.4 is distinguished from all other members of
      the high voltage-activated (HVA) Ca2+ channel family by lacking Ca2+-calmodulin
      dependent inactivation. In synaptic terminals of photoreceptors and bipolar
      cells, this feature is essential to translate graded membrane depolarizations
      into sustained Ca2+ influx and tonic glutamate release. The sequences conferring
      Ca2+-dependent inactivation (CDI) are conserved throughout the HVA calcium
      channel family, raising the question of how Cav1.4 manages to switch off CDI.
      Here, we identify an autoinhibitory domain in the distal C terminus of Cav1.4
      that serves to abolish CDI. We show that this domain (ICDI, inhibitor of CDI)
      uncouples the molecular machinery conferring CDI from the inactivation gate by
      binding to the EF hand motif in the proximal C terminus. Deletion of ICDI
      completely restores Ca2+-calmodulin-mediated CDI in Cav1.4. CDI can be switched
      off again in the truncated Cav1.4 channel by coexpression of ICDI, indicating
      that ICDI works as an autonomous unit. Furthermore, we show that in the Cav1.2 l
      type Ca2+-channel replacement of the distal C terminus by the corresponding
      sequence of Cav1.4 is sufficient to block CDI. This finding suggests that
      autoinhibition of CDI can be introduced principally into other Ca2+ channel
      types. Our data provide a previously undescribed perspective on the regulation of
      HVA calcium channels by Ca2+.

PMID- 17028173
TI  - A deletion defining a common Asian lineage of Mycobacterium tuberculosis
      associates with immune subversion.
AB  - Six major lineages of Mycobacterium tuberculosis appear preferentially
      transmitted amongst distinct ethnic groups. We identified a deletion affecting
      Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that
      coincidentally defines the East African-Indian lineage matching a major ethnic
      group in this city. In broth media, CH grew less rapidly and was less acidic and
      H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless,
      CH was not impaired in its ability to grow in human monocyte-derived macrophages.
      When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and
      more antiinflammatory IL-10 and IL-6 gene transcription and secretion from
      monocyte-derived macrophages. It thus appears that CH compensates microbiological
      attenuation by skewing the innate response toward phagocyte deactivation.
      Complementation of Rv1519, but none of nine additional genes absent from CH
      compared with the type strain, H37Rv, reversed the capacity of CH to elicit
      antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M.
      tuberculosis confers an immune subverting phenotype that contributes to the
      persistence and outbreak potential of this lineage.

PMID- 17028174
TI  - Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and
      AMPK, and is involved in AMPK and mTOR signaling.
AB  - Birt-Hogg-Dube syndrome, a hamartoma disorder characterized by benign tumors of
      the hair follicle, lung cysts, and renal neoplasia, is caused by germ-line
      mutations in the BHD(FLCN) gene, which encodes a tumor-suppressor protein,
      folliculin (FLCN), with unknown function. The tumor-suppressor proteins encoded
      by genes responsible for several other hamartoma syndromes, LKB1, TSC1/2, and
      PTEN, have been shown to be involved in the mammalian target of rapamycin (mTOR)
      signaling pathway. Here, we report the identification of the FLCN-interacting
      protein, FNIP1, and demonstrate its interaction with 5' AMP-activated protein
      kinase (AMPK), a key molecule for energy sensing that negatively regulates mTOR
      activity. FNIP1 was phosphorylated by AMPK, and its phosphorylation was reduced
      by AMPK inhibitors, which resulted in reduced FNIP1 expression. AMPK inhibitors
      also reduced FLCN phosphorylation. Moreover, FLCN phosphorylation was diminished
      by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression,
      suggesting that FLCN may be regulated by mTOR and AMPK signaling. Our data
      suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting
      partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK
      and mTOR signaling pathways.

PMID- 17028175
TI  - Inhomogeneous dynamics in confined water nanodroplets.
AB  - The effect of confinement on the dynamical properties of liquid water was studied
      by mid-infrared ultrafast pump-probe spectroscopy on HDO:D2O in reverse micelles.
      By preparing water-containing reverse micelles of different well defined sizes,
      we varied the degree of geometric confinement in water nanodroplets with radii
      ranging from 0.2 to 4.5 nm. We find that water molecules located near the
      interface confining the droplet exhibit slower vibrational energy relaxation and
      have a different spectral absorption than those located in the droplet core. As a
      result, we can measure the orientational dynamics of these different types of
      water with high selectivity. We observe that the water molecules in the core show
      similar orientational dynamics as bulk water and that the water layer solvating
      the interface is highly immobile.

PMID- 17028176
TI  - Chlamydial TARP is a bacterial nucleator of actin.
AB  - Chlamydia trachomatis entry into host cells results from a parasite-directed
      remodeling of the actin cytoskeleton. A type III secreted effector, TARP
      (translocated actin recruiting phosphoprotein), has been implicated in the
      recruitment of actin to the site of internalization. To elucidate the role of
      TARP in actin recruitment, we identified host cell proteins that associated with
      recombinant GST-TARP fusions. TARP directly associated with actin, and this
      interaction promoted actin nucleation as determined by in vitro polymerization
      assays. Domain analysis of TARP identified an actin-binding domain that bears
      structural and primary amino acid sequence similarity to WH2 domain family
      proteins. In addition, a proline-rich domain was found to promote TARP
      oligomerization and was required for TARP-dependent nucleation of new actin
      filaments. Our findings reveal a mechanism by which chlamydiae induce localized
      cytoskeletal changes by the translocated effector TARP during entry into host
      cells.

PMID- 17028177
TI  - Fronto-cerebellar systems are associated with infant motor and adult executive
      functions in healthy adults but not in schizophrenia.
AB  - Delineating longitudinal relationships between early developmental markers, adult
      cognitive function, and adult brain structure could clarify the pathogenesis of
      neurodevelopmental disorders such as schizophrenia. We aimed to identify brain
      structural correlates of infant motor development (IMD) and adult executive
      function in nonpsychotic adults and to test for abnormal associations between
      these measures in people with schizophrenia. Representative samples of
      nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn
      from the Northern Finland 1966 general population birth cohort. IMD was
      prospectively assessed at age 1 year; executive function testing and MRI were
      completed at age 33-35 years. We found that earlier motor development in infancy
      was correlated with superior executive function in nonpsychotic subjects. Earlier
      motor development was also normally associated with increased gray matter density
      in adult premotor cortex, striatum, and cerebellum and increased white matter
      density in frontal and parietal lobes. Adult executive function was normally
      associated with increased gray matter density in a fronto-cerebellar system that
      partially overlapped, but was not identical to, the gray matter regions normally
      associated with IMD. People with schizophrenia had relatively delayed IMD and
      impaired adult executive function in adulthood. Furthermore, they demonstrated no
      normative associations between fronto-cerebellar structure, IMD, or executive
      function. We conclude that frontal cortico-cerebellar systems correlated with
      adult executive function are anatomically related to systems associated with
      normal infant motor development. Disruption of this anatomical system may
      underlie both the early developmental and adult cognitive abnormalities in
      schizophrenia.

PMID- 17028178
TI  - The deubiquitinating enzyme Ubp2 modulates Rsp5-dependent Lys63-linked
      polyubiquitin conjugates in Saccharomyces cerevisiae.
AB  - The functions of Lys(63)-linked polyubiquitin chains are poorly understood, as
      are the enzymes that specifically generate Lys(63)-linked conjugates. Rsp5 is a
      HECT (homologous to E6AP C terminus) ubiquitin ligase involved in numerous
      processes, and an associated deubiquitinating enzyme, Ubp2, modulates its
      activity. A dramatic increase in Lys(63)-linked conjugates was observed in
      ubp2Delta cells. The formation of these was Rsp5-dependent, and ubp2Delta
      phenotypes could be suppressed by prevention of formation of Lys(63) conjugates.
      Cell wall integrity was impaired in rsp5-1 cells and in cells defective in
      Lys(63)-polyubiquitination, as assayed by calcofluor white sensitivity, and
      ubp2Delta and rup1Delta mutants suppressed the calcofluor white sensitivity of
      rsp5-1. A large fraction of the Lys(63) conjugates in ubp2Delta cells bound to
      Rsp5, and a proteomics approach was used to identify Rsp5 substrates subject to
      Ubp2 regulation. Two closely related proteins, Csr2 and Ecm21, were among the
      identified proteins. Both were efficiently Lys(63)-polyubiquitinated by Rsp5 and
      deubiquitinated by Ubp2. Together, these results indicate that Ubp2 modulates
      Lys(63)-polyubiquitination of Rsp5 substrates in vivo, including ubiquitination
      of two newly identified Rsp5 substrates.

PMID- 17028179
TI  - A multienzyme network functions in intestinal protein digestion by a
      platyhelminth parasite.
AB  - Proteases frequently function not only as individual enzymes but also in cascades
      or networks. A notable evolutionary switch occurred in one such protease network
      that is involved in protein digestion in the intestine. In vertebrates, this is
      largely the work of trypsin family serine proteases, whereas in invertebrates,
      cysteine proteases of the papain family and aspartic proteases assume the role.
      Utilizing a combination of protease class-specific inhibitors and RNA
      interference, we deconvoluted such a network of major endopeptidases functioning
      in invertebrate intestinal protein digestion, using the parasitic helminth,
      Schistosoma mansoni as an experimental model. We show that initial degradation of
      host blood proteins is ordered, occasionally redundant, and substrate-specific.
      Although inhibition of parasite cathepsin D had a greater effect on primary
      cleavage of hemoglobin, inhibition of cathepsin B predominated in albumin
      degradation. Nevertheless, in both cases, inhibitor combinations were
      synergistic. An asparaginyl endopeptidase (legumain) also synergized with
      cathepsin B and L in protein digestion, either by zymogen activation or
      facilitating substrate cleavage. This protease network operates optimally in
      acidic pH compartments either in the gut lumen or in vacuoles of the intestinal
      lining cells. Defining the role of each of these major enzymes now provides a
      clearer understanding of the function of a complex protease network that is
      conserved throughout invertebrate evolution. It also provides insights into which
      of these proteases are logical targets for development of chemotherapy for
      schistosomiasis, a major global health problem.

PMID- 17028180
TI  - Transcriptional regulation by Foxp3 is associated with direct promoter occupancy
      and modulation of histone acetylation.
AB  - Regulatory T cells (T(reg)) express Foxp3, a forkhead family member that is
      necessary and sufficient for T(reg) lineage choice and function. Ectopic
      expression of Foxp3 in non-T(reg) leads to repression of the interleukin 2 (IL-2)
      and interferon gamma (IFNgamma) genes, gain of suppressor function, and induction
      of genes such as CD25, GITR, and CTLA-4, but the mode by which Foxp3 enforces
      this program is unclear. Using chromatin immunoprecipitation, we have
      demonstrated that Foxp3 binds to the endogenous IL-2 and IFNgamma loci in T
      cells, but only after T cell receptor stimulation. This activation-induced Foxp3
      binding was abrogated by cyclosporin A, suggesting a role for the phosphatase
      calcineurin in Foxp3 function. We have also shown that binding of Foxp3 to the IL
      2 and IFNgamma genes induces active deacetylation of histone H3, a process that
      inhibits chromatin remodeling and opposes gene transcription. Conversely, binding
      of Foxp3 to the GITR, CD25, and CTLA-4 genes results in increased histone
      acetylation. These data indicate that Foxp3 may regulate transcription through
      direct chromatin remodeling and show that Foxp3 function is influenced by signals
      from the TCR.

PMID- 17028181
TI  - Expression of expanded polyglutamine proteins suppresses the activation of
      transcription factor NFkappaB.
AB  - A major pathological hallmark of the polyglutamine diseases is the formation of
      neuronal intranuclear inclusions of the disease proteins that are ubiquitinated
      and often associated with various transcription factors, chaperones, and
      proteasome components. However, how the expanded polyglutamine proteins or their
      aggregates elicit complex pathogenic responses in the neuronal cells is not fully
      understood. Here, we have demonstrated that the expression of expanded
      polyglutamine proteins down-regulated the NFkappaB-dependent transcriptional
      activity. The expression of expanded polyglutamine proteins increased the
      stability and the levels of IkappaB-alpha and its phosphorylated derivatives. We
      have also found that various NFkappaB subunits and IkappaB-alpha aberrantly
      interacted with the expanded polyglutamine proteins and associated with their
      aggregates. Finally, we have shown that several NFkappaB-dependent genes are down
      regulated in the expanded polyglutamine protein-expressing cells and down
      regulation of NFkappaB activity enhances expanded polyglutamine protein-induced
      cell death. Because the NFkappaB pathway plays a very important role in cell
      survival, altered regulation of this pathway in expanded polyglutamine protein
      expressing cells might be linked with the disease pathogenesis.

PMID- 17028182
TI  - Structural insights into the design of nonpeptidic isothiazolidinone-containing
      inhibitors of protein-tyrosine phosphatase 1B.
AB  - Structural analyses of the protein-tyrosine phosphatase 1B (PTP1B) active site
      and inhibitor complexes have aided in optimization of a peptide inhibitor
      containing the novel (S)-isothiazolidinone (IZD) phosphonate mimetic. Potency and
      permeability were simultaneously improved by replacing the polar peptidic
      backbone of the inhibitor with nonpeptidic moieties. The C-terminal primary amide
      was replaced with a benzimidazole ring, which hydrogen bonds to the carboxylate
      of Asp(48), and the N terminus of the peptide was replaced with an aryl
      sulfonamide, which hydrogen bonds to Asp(48) and the backbone NH of Arg(47) via a
      water molecule. Although both substituents retain the favorable hydrogen bonding
      network of the peptide scaffold, their aryl rings interact weakly with the
      protein. The aryl ring of benzimidazole is partially solvent exposed and only
      participates in van der Waals interactions with Phe(182) of the flap. The aryl
      ring of aryl sulfonamide adopts an unexpected conformation and only participates
      in intramolecular pi-stacking interactions with the benzimidazole ring. These
      results explain the flat SAR for substitutions on both rings and the reason why
      unsubstituted moieties were selected as candidates. Finally, substituents ortho
      to the IZD heterocycle on the aryl ring of the IZD-phenyl moiety bind in a small
      narrow site adjacent to the primary phosphate binding pocket. The crystal
      structure of an o-chloro derivative reveals that chlorine interacts extensively
      with residues in the small site. The structural insights that have led to the
      discovery of potent benzimidazole aryl sulfonamide o-substituted derivatives are
      discussed in detail.

PMID- 17028183
TI  - Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole
      complex reveals new azole drug-P450 binding mode.
AB  - Azole and triazole drugs are cytochrome P450 inhibitors widely used as fungal
      antibiotics and possessing potent antimycobacterial activity. We present here the
      crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121 in complex
      with the triazole drug fluconazole, revealing a new azole heme ligation mode. In
      contrast to other structurally characterized cytochrome P450 azole complexes,
      where the azole nitrogen directly coordinates the heme iron, in CYP121
      fluconazole does not displace the aqua sixth heme ligand but occupies a position
      that allows formation of a direct hydrogen bond to the aqua sixth heme ligand.
      Direct ligation of fluconazole to the heme iron is observed in a minority of
      CYP121 molecules, albeit with severe deviations from ideal geometry due to close
      contacts with active site residues. Analysis of both ligand-on and -off
      structures reveals the relative position of active site residues derived from the
      I-helix is a key determinant in the relative ratio of on and off states.
      Regardless, both ligand-bound states lead to P450 inactivation by active site
      occlusion. This previously unrecognized means of P450 inactivation is consistent
      with spectroscopic analyses in both solution and in the crystalline form and
      raises important questions relating to interaction of azoles with both pathogen
      and human P450s.

PMID- 17028184
TI  - L4-33K, an adenovirus-encoded alternative RNA splicing factor.
AB  - Splicing of the adenovirus IIIa mRNA is subjected to a strict temporal regulation
      during virus infection such that efficient IIIa 3' splice site usage is confined
      to the late phase of the infectious cycle. Here we show that the adenovirus L4
      33K protein functions as a virus-encoded RNA splicing factor that preferentially
      activates splicing of transcripts with a weak 3' splice site sequence context, a
      sequence configuration that is shared by many of the late adenovirus 3' splice
      sites. Furthermore, we show that L4-33K activates IIIa splicing through the IIIa
      virus infection-dependent splicing enhancer element (3VDE). This element was
      previously shown to be the minimal element, both necessary and sufficient, for
      activation of IIIa splicing in the context of an adenovirus-infected cell. L4-33K
      stimulates an early step in spliceosome assembly and appears to be the only viral
      protein necessary to convert a nuclear extract prepared from uninfected HeLa
      cells to an extract with splicing properties very similar to a nuclear extract
      prepared from adenovirus late-infected cells. Collectively, our results suggest
      that L4-33K is the key viral protein required to activate the early to late
      switch in adenovirus major late L1 alternative splicing.

PMID- 17028185
TI  - Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro
      apoptotic.
AB  - The transcription factor STAT3 is activated by interleukin-6-related cytokines
      and has been implicated as an oncogene; it promotes cell proliferation and is
      anti-apoptotic. However, in some cases, STAT3 has been shown to be pro-apoptotic,
      especially in mammary epithelial cells. In this report, we generated SOCS3
      deficient murine embryonic fibroblasts (MEFs), in which STAT3 activation is
      extremely enhanced and prolonged. We found that LIF induces caspase-3 activation
      and apoptosis of SOCS3(-/-) MEFs. Exogenous expression of the dominant negative
      form of STAT3 but not STAT1 suppressed LIF-induced apoptosis of SOCS3(-/-) MEFs,
      indicating that STAT3 plays a critical role in apoptosis induction. As shown in
      mammary gland epithelial cells, expression of the phosphatidylinositol 3-kinase
      regulatory subunits p50alpha and p55alpha was induced in response to LIF in
      SOCS3(-/-) MEFs but not in wild-type MEFs, and Akt/protein kinase B activity was
      substantially reduced in SOCS3(-/-) MEFs. Furthermore, we found that some of the
      STAT3 target genes related to apoptosis and proliferation, such as Bcl-2 and
      cyclin D1, were repressed upon LIF treatment in SOCS3(-/-) cells. Not only the up
      regulation of p50alpha and p55alpha but also the repression of cyclin D1 and Bcl
      2 in SOCS3(-/-) MEFs was inhibited by dominant negative STAT3. These data suggest
      that prolonged activation of STAT3 could induce apoptosis/growth arrest rather
      than anti-apoptosis and proliferation in certain cases, and SOCS3 is a critical
      regulator of this balance.

PMID- 17028186
TI  - Molecular and functional characterization of a soluble form of oncostatin
      M/interleukin-31 shared receptor.
AB  - Activation of the signaling transduction pathways mediated by oncostatin M (OSM)
      requires the binding of the cytokine to either type I OSM receptor (leukemia
      inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the
      present work we have developed an enzyme-linked immunosorbent assay detecting a
      soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma
      tumor cell lines. sOSMR was also present in sera of healthy individuals, with
      increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA
      was carried out, and it encoded for a 70-kDa protein consisting of a half
      cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin
      like domain, and the first half of a second cytokine binding domain with
      cysteines in fixed positions. Analysis of the soluble receptor distribution
      revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR
      was able to bind OSM and interleukin-31 when associated to soluble gp130 or
      soluble interleukin-31R, respectively, and to neutralize both cytokine
      properties. We have also shown that OSM could positively regulate the synthesis
      of its own soluble receptor in tumor cells.

PMID- 17028187
TI  - Structural characterization of a blue chromoprotein and its yellow mutant from
      the sea anemone Cnidopus japonicus.
AB  - Green fluorescent protein (GFP) and its relatives (GFP protein family) have been
      isolated from marine organisms such as jellyfish and corals that belong to the
      phylum Cnidaria (stinging aquatic invertebrates). They are intrinsically
      fluorescent proteins. In search of new members of the family of green fluorescent
      protein family, we identified a non-fluorescent chromoprotein from the Cnidopus
      japonicus species of sea anemone that possesses 45% sequence identity to dsRed (a
      red fluorescent protein). This newly identified blue color protein has an
      absorbance maximum of 610 nm and is hereafter referred to as cjBlue.
      Determination of the cjBlue 1.8 A crystal structure revealed a chromophore
      comprised of Gln(63)-Tyr(64)-Gly(65). The ring stacking between Tyr(64) and
      His(197) stabilized the cjBlue trans chromophore conformation along the Calpha2
      Cbeta2 bond of 5-[(4-hydroxyphenyl)methylene]-imidazolinone, which closely
      resembled that of the "Kindling Fluorescent Protein" and Rtms5. Replacement of
      Tyr(64) with Leu in wild-type cjBlue produced a visible color change from blue to
      yellow with a new absorbance maximum of 417 nm. Interestingly, the crystal
      structure of the yellow mutant Y64L revealed two His(197) imidazole ring
      orientations, suggesting a flip-flop interconversion between the two
      conformations in solution. We conclude that the dynamics and structure of the
      chromophore are both essential for the optical appearance of these color
      proteins.

PMID- 17028188
TI  - Oncostatin M inhibits adipogenesis through the RAS/ERK and STAT5 signaling
      pathways.
AB  - Adipocytes play a key role in energy homeostasis and several cytokines have been
      shown to regulate adipogenesis. While the interleukin (IL)-6 family of cytokines
      was previously reported to be involved in adipogenesis, roles of this family in
      adipogenesis and their mechanisms of action are not fully understood. Here we
      show that among the IL-6 family, oncostatin M (OSM) most strongly inhibits
      adipogenesis of 3T3-L1 cells and mouse embryonic fibroblasts (MEFs). We also
      demonstrate that OSM inhibits adipogenesis through the Ras/extracellular signal
      regulated kinase (ERK) and signal transducer and activator of transcription
      (STAT) 5 signaling pathways. In addition, OSM inhibits the early phase of the
      differentiation without affecting cell proliferation throughout adipogenesis
      including mitotic clonal expansion. CCAAT/enhancer-binding protein (C/EBP) alpha,
      C/EBPbeta, and peroxisome proliferator-activated receptor (PPAR) gamma are known
      to be required for adipogenesis. Expression of C/EBPalpha and PPARgamma was
      almost completely abrogated by OSM. In contrast, neither the mRNA nor protein
      level of C/EBPbeta was affected by OSM. Forced expression of C/EBPbeta induced
      differentiation in the presence of troglitazone, and OSM inhibited this C/EBPbeta
      induced differentiation. Taken together, our results indicate that OSM inhibits
      the onset of terminal differentiation of adipocytes through the Ras/ERK and STAT5
      signaling pathways by possibly regulating C/EBPbeta activity.

PMID- 17028189
TI  - Trim5alpha accelerates degradation of cytosolic capsid associated with productive
      HIV-1 entry.
AB  - The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross
      species restriction in human immunodeficiency virus type 1 (HIV-1) infection of
      non-human cells, but the mechanism by which this occurs remains to be fully
      elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more
      rapidly degraded in cells expressing monkey TRIM5alpha than in cells expressing
      human TRIM5alpha. Other proteins encoded by Gag and Pol are not subject to
      TRIM5alpha-mediated accelerated degradation. The accelerated CA degradation by
      TRIM5alpha apparently occurs via a nonproteosomal pathway. TRIM5alpha selectively
      accelerates degradation of the CA population, which reached the cytosol of
      restrictive cells, but not the CA population, which ended into the vesicular
      compartment. Given that cytosolic CA represents "productively" entered cores,
      whereas vesicular CA represents "nonproductively" entered cores, our findings
      suggest that TRIM5alpha interrupts the infectious pathway of HIV-1 by acting on
      the incoming cytosolic CA. The mode of viral entry does not influence the
      accelerated degradation of cytosolic CA by TRIM5alpha. Thus, this study reveals a
      correlation between TRIM5alpha-mediated HIV-1 restriction and a selective
      degradation of cytosolic CA normally associated with productive viral entry.

PMID- 17028190
TI  - Mechanistic and structural studies of apoform, binary, and ternary complexes of
      the Arabidopsis alkenal double bond reductase At5g16970.
AB  - In this study, we determined the crystal structures of the apoform, binary, and
      ternary complexes of the Arabidopsis alkenal double bond reductase encoded by
      At5g16970. This protein, one of 11 homologues in Arabidopsis thaliana, is most
      closely related to the Pinus taeda phenylpropenal double bond reductase, involved
      in, for example, heartwood formation. Both enzymes also have essential roles in
      plant defense, and can function by catalyzing the reduction of the 7-8-double
      bond of phenylpropanal substrates, such as p-coumaryl and coniferyl aldehydes in
      vitro. At5g16970 is also capable of reducing toxic substrates with the same
      alkenal functionality, such as 4-hydroxy-(2E)-nonenal. The overall fold of
      At5g16970 is similar to that of the zinc-independent medium chain
      dehydrogenase/reductase superfamily, the members of which have two domains and
      are dimeric in nature, i.e. in contrast to their original classification as being
      zinc-containing oxidoreductases. As provisionally anticipated from the kinetic
      data, the shape of the binding pocket can readily accommodate p-coumaryl
      aldehyde, coniferyl aldehyde, 4-hydroxy-(2E)-nonenal, and 2-alkenals. However,
      the enzyme kinetic data among these potential substrates differ, favoring p
      coumaryl aldehyde. Tyr-260 is provisionally proposed to function as a general
      acid/base for hydride transfer. A catalytic mechanism for this reduction, and its
      applicability to related important detoxification mammalian proteins, is also
      proposed.

PMID- 17028191
TI  - Intracranial microenvironment reveals independent opposing functions of host
      alphaVbeta3 expression on glioma growth and angiogenesis.
AB  - alphaVbeta3 integrins are overexpressed in the host-derived vasculature of
      glioblastoma multiform (GBM) and are believed to contribute to angiogenesis and
      tumor growth. To directly address the role of host alphaVbeta3 expression in GBM
      growth and behavior, we intracranially implanted integrin beta3-expressing GBM
      cells into beta3 wild type (WT) or beta3 knock out (KO) mice and monitored
      angiogenesis and growth. GBM in beta3 WT animals had a vessel density greater
      than that in beta3 KO animals, consistent with a pro-angiogenic, pro-tumorigenic
      view of host integrin function. GBM in beta3 WT animals, however, were no larger
      than those in beta3 KO animals, because GBM in beta3WT animals were infiltrated
      with a higher number of tumor necrosis factor alpha-secreting, apoptosis-inducing
      macrophages than the tumors in the corresponding beta3 KO animals. The tumor
      suppressive effects of host beta3 expression could be reversed by macrophage
      depletion or by transplantation of bone marrow from beta3 KO animals into beta3
      WT animals, both of which significantly increased tumor growth independently of
      tumor vessel density. Taken together, these results show that host alphaVbeta3
      integrin expression has opposing actions in the intracranial setting, enhancing
      tumor vascularization and growth while independently enhancing macrophage
      mediated tumor elimination. Appropriate management of these functions could lead
      to enhanced efficacy of anti-integrin based therapies for glioma.

PMID- 17028192
TI  - An allosteric activator of glucokinase impairs the interaction of glucokinase and
      glucokinase regulatory protein and regulates glucose metabolism.
AB  - Glucokinase (GK) plays a key role in the control of blood glucose homeostasis. We
      identified a small molecule GK activator, compound A, that increased the glucose
      affinity and maximal velocity (V(max)) of GK. Compound A augmented insulin
      secretion from isolated rat islets and enhanced glucose utilization in primary
      cultured rat hepatocytes. In rat oral glucose tolerance tests, orally
      administrated compound A lowered plasma glucose elevation with a concomitant
      increase in plasma insulin and hepatic glycogen. In liver, GK activity is acutely
      controlled by its association to the glucokinase regulatory protein (GKRP). In
      order to decipher the molecular aspects of how GK activator affects the shuttling
      of GK between nucleus and cytoplasm, the effect of compound A on GK-GKRP
      interaction was further investigated. Compound A increased the level of
      cytoplasmic GK in both isolated rat primary hepatocytes and the liver tissues
      from rats. Experiments in a cell-free system revealed that compound A interacted
      with glucose-bound free GK, thereby impairing the association of GK and GKRP. On
      the other hand, compound A did not bind to glucose-unbound GK or GKRP-associated
      GK. Furthermore, we found that glucose-dependent GK-GKRP interaction also
      required ATP. Given the combined prominent role of GK on insulin secretion and
      hepatic glucose metabolism where the GK-GKRP mechanism is involved, activation of
      GK has a new therapeutic potential in the treatment of type 2 diabetes.

PMID- 17028193
TI  - Overexpression of rat long chain acyl-coa synthetase 1 alters fatty acid
      metabolism in rat primary hepatocytes.
AB  - Long chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide
      substrates for both anabolic and catabolic pathways. We have hypothesized that
      each of the five ACSL isoforms partitions FA toward specific downstream pathways.
      Acsl1 mRNA is increased in cells under both lipogenic and oxidative conditions.
      To elucidate the role of ACSL1 in hepatic lipid metabolism, we overexpressed an
      Acsl1 adenovirus construct (Ad-Acsl1) in rat primary hepatocytes. Ad-ACSL1,
      located on the endoplasmic reticulum but not on mitochondria or plasma membrane,
      increased ACS specific activity 3.7-fold. With 100 or 750 mum [1-(14)C]oleate, Ad
      Acsl1 increased oleate incorporation into diacylglycerol and phospholipids,
      particularly phosphatidylethanolamine and phosphatidylinositol, and decreased
      incorporation into cholesterol esters and secreted triacylglycerol. Ad-Acsl1 did
      not alter oleate incorporation into triacylglycerol, beta-oxidation products, or
      total amount of FA metabolized. In pulse-chase experiments to examine the effects
      of Ad-Acsl1 on lipid turnover, more labeled triacylglycerol and phospholipid, but
      less labeled diacylglycerol, remained in Ad-Acsl1 cells, suggesting that ACSL1
      increased reacylation of hydrolyzed oleate derived from triacylglycerol and
      diacylglycerol. In addition, less hydrolyzed oleate was used for cholesterol
      ester synthesis and beta-oxidation. The increase in [1,2,3-(3)H]glycerol
      incorporation into diacylglycerol and phospholipid was similar to the increase
      with [(14)C]oleate labeling suggesting that ACSL1 increased de novo synthesis.
      Labeling Ad-Acsl1 cells with [(14)C]acetate increased triacylglycerol synthesis
      but did not channel endogenous FA away from cholesterol ester synthesis. Thus,
      consistent with the hypothesis that individual ACSLs partition FA, Ad-Acsl1
      increased FA reacylation and channeled FA toward diacylglycerol and phospholipid
      synthesis and away from cholesterol ester synthesis.

PMID- 17028194
TI  - Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of
      tumor cells.
AB  - To study the role of p38 mitogen-activated protein kinase (p38) activity during
      the process of metastasis, p38alpha(+/-) mice were subjected to an in vivo
      metastasis assay. The number of lung colonies of tumor cells intravenously
      injected in p38alpha(+/-) mice was markedly decreased compared with that in wild
      type (WT) mice. On the other hand, the time-dependent increase in tumor volume
      after subcutaneous tumor cells transplantation was comparable between WT and
      p38alpha(+/-) mice. Platelets of p38alpha(+/-) mice were poorly bound to tumor
      cells in vitro and in vivo compared with those of WT mice. E- and P-selectin
      mRNAs were markedly induced in the lung after intravenous injection of tumor
      cells. However, the induction of these selectin mRNAs in p38alpha(+/-) mice was
      weaker than that in WT mice. Furthermore, the resting expression levels of E
      selectin in lung endothelial cells and P-selectin in platelets of p38alpha(+/-)
      mice were suppressed compared with those of WT mice. The number of tumor cells
      attached on lung endothelial cells of p38alpha(+/-) mice was significantly
      reduced compared with that of WT mice. The transmigrating activity of tumor cells
      through lung endothelial cells of p38alpha(+/-) mice was similar to that of WT
      mice. These results suggest that p38alpha plays an important role in
      extravasation of tumor cells, possibly through regulating the formation of tumor
      platelet aggregates and their interaction with the endothelium involved in a step
      of hematogenous metastasis.

PMID- 17028195
TI  - Mitochondrial creatine kinase activity prevents reactive oxygen species
      generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling
      activity.
AB  - As recently demonstrated by our group (da-Silva, W. S., Gomez-Puyou, A., Gomez
      Puyou, M. T., Moreno-Sanchez, R., De Felice, F. G., de Meis, L., Oliveira, M. F.,
      and Galina, A. (2004) J. Biol. Chem. 279, 39846-39855) mitochondrial hexokinase
      activity (mt-HK) plays a preventive antioxidant role because of steady-state ADP
      re-cycling through the inner mitochondrial membrane in rat brain. In the present
      work we show that ADP re-cycling accomplished by the mitochondrial creatine
      kinase (mt-CK) regulates reactive oxygen species (ROS) generation, particularly
      in high glucose concentrations. Activation of mt-CK by creatine (Cr) and ATP or
      ADP, induced a state 3-like respiration in isolated brain mitochondria and
      prevention of H(2)O(2) production obeyed the steady-state kinetics of the enzyme
      to phosphorylate Cr. The extension of the preventive antioxidant role of mt-CK
      depended on the phosphocreatine (PCr)/Cr ratio. Rat liver mitochondria, which
      lack mt-CK activity, only reduced state 4-induced H(2)O(2) generation when 1
      order of magnitude more exogenous CK activity was added to the medium. Simulation
      of hyperglycemic conditions, by the inclusion of glucose 6-phosphate in
      mitochondria performing 2-deoxyglucose phosphorylation via mt-HK, induced
      H(2)O(2) production in a Cr-sensitive manner. Simulation of hyperglycemia in
      embryonic rat brain cortical neurons increased both DeltaPsi(m) and ROS
      production and both parameters were decreased by the previous inclusion of Cr.
      Taken together, the results presented here indicate that mitochondrial kinase
      activity performed a key role as a preventive antioxidant against oxidative
      stress, reducing mitochondrial ROS generation through an ADP-recycling mechanism.

PMID- 17028196
TI  - Adenomatous polyposis coli control of C-terminal binding protein-1 stability
      regulates expression of intestinal retinol dehydrogenases.
AB  - Mutations in the human adenomatous polyposis coli (APC) gene are thought to
      initiate colorectal tumorigenesis. The tumor suppressor function of APC is
      attributed primarily to its ability to regulate the WNT pathway by targeting the
      destruction of beta-catenin. We report here a novel role for APC in regulating
      degradation of the transcriptional co-repressor C-terminal-binding protein-1
      (CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the
      expression of intestinal retinol dehydrogenases, which are required for retinoic
      acid production and intestinal differentiation. In support of a role for CtBP1 in
      initiation of colorectal cancer, adenomas taken from individuals with familial
      adenomatous polyposis contain high levels of CtBP1 protein in comparison with
      matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved
      between humans and zebrafish and provides a mechanistic model explaining APC
      control of intestinal retinoic acid biosynthesis.

PMID- 17028197
TI  - Low molecular weight fucoidan increases VEGF165-induced endothelial cell
      migration by enhancing VEGF165 binding to VEGFR-2 and NRP1.
AB  - Therapeutic induction of angiogenesis is a potential treatment for chronic
      ischemia. Heparan sulfate proteoglycans are known to play an important role by
      their interactions with proangiogenic growth factors such as vascular endothelial
      growth factor (VEGF). Low molecular weight fucoidan (LMWF), a sulfated
      polysaccharide from brown seaweeds that mimic some biological activities of
      heparin, has been shown recently to promote revascularization in rat critical
      hindlimb ischemia. In this report, we first used cultured human endothelial cells
      (ECs) to investigate the possible ability of LMWF to enhance the actions of
      VEGF(165). Data showed that LMWF greatly enhances EC tube formation in growth
      factor reduced matrigel. LMWF is a strong enhancer of VEGF(165)-induced EC
      chemotaxis, but not proliferation. In addition, LMWF has no effect on VEGF(121)
      induced EC migration, a VEGF isoform that does not bind to heparan sulfate
      proteoglycans. Then, with binding studies using (125)I-VEGF(165), we observed
      that LMWF enhances the binding of VEGF(165) to recombinant VEGFR-2 and Neuropilin
      1 (NRP1), but not to VEGFR-1. Surface plasmon resonance analysis showed that LMWF
      binds with high affinity to VEGF(165) (1.2 nm) and its receptors (5-20 nm), but
      not to VEGF(121). Pre-injection of LMWF on immobilized receptors shows that
      VEGF(165) has the highest affinity for VEGFR-2 and NRP1, as compared with VEGFR
      1. Overall, the effects of LMWF were much more pronounced than those of LMW
      heparin. These findings suggested an efficient mechanism of action of LMWF by
      promoting VEGF(165) binding to VEGFR-2 and NRP1 on ECs that could help in
      stimulating therapeutic revascularization.

PMID- 17028198
TI  - RalA-exocyst-dependent recycling endosome trafficking is required for the
      completion of cytokinesis.
AB  - In eukaryotic cells, recycling endosome-mediated trafficking contributes to the
      completion of cytokinesis, in a manner under the control of the centrosome. We
      report that the exocyst complex and its interacting GTPase RalA play a critical
      role in this polarized trafficking process. RalA resides in the recycling
      endosome and relocates from the pericentrosomal region to key cytokinetic
      structures including the cleavage furrow, and later, the abscission site. This
      event is coupled to the dynamic redistribution of the exocyst proteins. These
      associate with the centrosome in interphase and concentrate on the central
      spindle/midbody during cytokinesis. Disruption of RalA-exocyst function leads to
      cytokinesis failure in late stages, particularly abscission, resembling the
      cytokinesis defects induced by loss of centrosome function. These data suggest
      that RalA and the exocyst may regulate vesicle delivery to the centrosome-related
      abscission site during the terminal stage of cytokinesis, implicating RalA as a
      critical regulator of cell cycle progression.

PMID- 17028199
TI  - Sialidase expression in activated human T lymphocytes influences production of
      IFN-gamma.
AB  - Sialidases influence cellular activity by removing terminal sialic acid from
      glycoproteins and glycolipids. Four genetically distinct sialidases (Neu1-4) have
      been identified in mammalian cells. In this study, we demonstrate that only
      lysosomal Neu1 and plasma membrane-associated Neu3 are detected in freshly
      isolated and activated human T lymphocytes. Activation of lymphocytes by exposure
      to anti-CD3 and anti-CD28 IgG resulted in a ninefold increase in Neu1-specific
      activity after growth of cells in culture for 5 days. In contrast, the activity
      of Neu3 changed minimally in activated lymphocytes. The increase in Neu1 enzyme
      activity correlated with increased synthesis of Neu1-specific mRNA. Neu1 was
      present on the surface of freshly isolated and activated CD4 and CD8 T
      lymphocytes, as determined by staining intact cells with anti-Neu1 IgG and
      analysis by flow cytometry and by Western blot analysis of biotin-labeled cell
      surface proteins. Cell surface Neu1 was found tightly associated with a subunit
      of protective protein/cathepsin A (PPCA). Compared with freshly isolated
      lymphocytes, activated cells expressed more surface binding sites for galactose
      recognizing lectins Erythrina cristagalli (ECA) and Arachis hypogaea. Growth of
      cells in the presence of sialidase inhibitors 2,3-dehydro-2-deoxy-N
      acetylneuraminic acid or 4-guanidino-2-deoxy-2,3-dehydro-N-acetylneuraminic acid
      resulted in a smaller increase in number of ECA-binding sites and a greater
      amount of cell surface sialic acid in activated cells. Inhibition of sialidase
      activity also resulted in reduced expression of IFN-gamma in activated cells. The
      down-regulation of IFN-gamma occurred at the transcriptional level. Thus,
      sialidase activity in activated T lymphocytes contributes to the hyposialylation
      of specific cell surface glycoconjugates and to the production of IFN-gamma.

PMID- 17028200
TI  - Regulatory T cell-mediated suppression: potential role of ICER.
AB  - How regulatory T (TR) cells dampen T cell responses remains unclear. Multiple
      modes of action have been proposed, including cell contact-dependent and/or
      cytokine-dependent mechanisms. Suppression may involve direct contact between TR
      cells and responder T cells. Alternatively, TR cells may act on dendritic cells
      to reduce their ability to prime T cells by modulating costimulation, inducing
      the secretion of suppressive cytokines or the increase of tryptophan metabolism.
      Here, we review emerging, novel mechanisms involved in contact-dependent, TR
      mediated suppression of IL-2 production in responder CD25- T lymphocytes and the
      potential involvement of inducible cAMP early repressor (ICER) in this
      suppression. Finally, cytokines such as TGF-beta and IL-10, produced by TR cells
      or other cells, may exert local suppression, which can be conveyed by basic
      mechanism(s) acting in a similar manner as contact-dependent, TR-mediated
      suppression.

PMID- 17028201
TI  - The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection.
AB  - Pseudomonas is one of the leading causes of contact lens-related microbial
      keratitis. Despite the use of antibiotics, the host inflammatory response
      continues to cause damage to the cornea, which may lead to blindness. CXCR2
      binding chemokines have been implicated in the pathogenesis of Pseudomonas
      keratitis, and the exact role of this receptor remains to be elucidated. Corneas
      of CXCR2 knockout and wild-type mice (Cmkar 2-/- and Cmkar 2+/+) were scratched,
      and 2x10(6) CFU/mL Pseudomonas 6294 or 6206 was added to corneas. Twenty-four
      hours postinfection, mice were killed, and eyes were harvested for enumeration of
      bacteria, myeloperoxidase (MPO) levels, and inflammatory mediators. Cmkar 2-/-
      had 20- to 100-fold more bacteria than Cmkar 2+/+ mice. There were no differences
      in MPO levels between gene knockout and Cmkar 2+/+ mice. Histology revealed PMN
      were restricted to the limbal area. Levels of CXCR2 chemokines (keratinocyte
      derived chemokine and MIP-2) were elevated significantly in gene knockout mice. A
      lack of CXCR2 leads to an inability to control bacterial numbers as a result of
      the inability of PMN to reach the site of infection in the avascular cornea.
      These results imply that CXCR2 is critical to the extravasation of neutrophils
      into the avascular cornea.

PMID- 17028202
TI  - The proteolytic function of the Arabidopsis 26S proteasome is required for
      specifying leaf adaxial identity.
AB  - Polarity formation is central to leaf morphogenesis, and several key genes that
      function in adaxial-abaxial polarity establishment have been identified and
      characterized extensively. We previously reported that Arabidopsis thaliana
      ASYMMERTIC LEAVES1 (AS1) and AS2 are important in promoting leaf adaxial fates.
      We obtained an as2 enhancer mutant, asymmetric leaves enhancer3 (ae3), which
      demonstrated pleiotropic plant phenotypes, including a defective adaxial identity
      in some leaves. The ae3 as2 double mutant displayed severely abaxialized leaves,
      which were accompanied by elevated levels of leaf abaxial promoting genes
      FILAMENTOUS FLOWER, YABBY3, KANADI1 (KAN1), and KAN2 and a reduced level of the
      adaxial promoting gene REVOLUTA. We identified AE3, which encodes a putative 26S
      proteasome subunit RPN8a. Furthermore, double mutant combinations of as2 with
      other 26S subunit mutations, including rpt2a, rpt4a, rpt5a, rpn1a, rpn9a, pad1,
      and pbe1, all displayed comparable phenotypes with those of ae3 as2, albeit with
      varying phenotypic severity. Since these mutated genes encode subunits that are
      located in different parts of the 26S proteasome, it is possible that the
      proteolytic function of the 26S holoenzyme is involved in leaf polarity
      formation. Together, our findings reveal that posttranslational regulation is
      essential in proper leaf patterning.

PMID- 17028203
TI  - The tomato NBARC-LRR protein Prf interacts with Pto kinase in vivo to regulate
      specific plant immunity.
AB  - Immunity in tomato (Solanum lycopersicum) to Pseudomonas syringae bacteria
      expressing the effector proteins AvrPto and AvrPtoB requires both Pto kinase and
      the NBARC-LRR (for nucleotide binding domain shared by Apaf-1, certain R gene
      products, and CED-4 fused to C-terminal leucine-rich repeats) protein Prf. Pto
      plays a direct role in effector recognition within the host cytoplasm, but the
      role of Prf is unknown. We show that Pto and Prf are coincident in the signal
      transduction pathway that controls ligand-independent signaling. Pto and Prf
      associate in a coregulatory interaction that requires Pto kinase activity and N
      myristoylation for signaling. Pto interacts with a unique Prf N-terminal domain
      outside of the NBARC-LRR domain and resides in a high molecular weight
      recognition complex dependent on the presence of Prf. In this complex, both Pto
      and Prf contribute to specific recognition of AvrPtoB. The data suggest that the
      role of Pto is confined to the regulation of Prf and that the bacterial effectors
      have evolved to target this coregulatory molecular switch.

PMID- 17028204
TI  - The Medicago truncatula CRE1 cytokinin receptor regulates lateral root
      development and early symbiotic interaction with Sinorhizobium meliloti.
AB  - Legumes develop different types of lateral organs from their primary root,
      lateral roots and nodules, the latter depending on a symbiotic interaction with
      Sinorhizobium meliloti. Phytohormones have been shown to function in the control
      of these organogeneses. However, related signaling pathways have not been
      identified in legumes. We cloned and characterized the expression of Medicago
      truncatula genes encoding members of cytokinin signaling pathways. RNA
      interference of the cytokinin receptor homolog Cytokinin Response1 (Mt CRE1) led
      to cytokinin-insensitive roots, which showed an increased number of lateral roots
      and a strong reduction in nodulation. Both the progression of S. meliloti
      infection and nodule primordia formation were affected. We also identified two
      cytokinin signaling response regulator genes, Mt RR1 and Mt RR4, which are
      induced early during the symbiotic interaction. Induction of these genes by S.
      meliloti infection is altered in mutants affected in the Nod factor signaling
      pathway; conversely, cytokinin regulation of the early nodulin Nodule Inception1
      (Mt NIN) depends on Mt CRE1. Hence, cytokinin signaling mediated by a single
      receptor, Mt CRE1, leads to an opposite control of symbiotic nodule and lateral
      root organogenesis. Mt NIN, Mt RR1, and Mt RR4 define a common pathway activated
      during early S. meliloti interaction, allowing crosstalk between plant cytokinins
      and bacterial Nod factors signals.

PMID- 17028205
TI  - Loading of Arabidopsis centromeric histone CENH3 occurs mainly during G2 and
      requires the presence of the histone fold domain.
AB  - The centromeric histone H3 (CENH3) substitutes histone H3 within the nucleosomes
      of active centromeres in all eukaryotes. CENH3 deposition at centromeres is
      needed to assemble the kinetochore, a complex of conserved proteins responsible
      for correct chromosome segregation during nuclear division. Histones of regular
      nucleosomes are loaded during replication in S phase, while CENH3 deposition
      deviates from this pattern in yeast, human, and Drosophila melanogaster cells.
      Little is known about when and how CENH3 targets centromeric loci. Therefore, we
      determined the location and quantity of recombinant enhanced yellow fluorescent
      protein (EYFP)-CENH3 in mitotic root and endopolyploid leaf nuclei of transgenic
      Arabidopsis thaliana cells. Our data indicate significant loading of A. thaliana
      CENH3 during G2 (before splitting into sister kinetochores) rather than during
      the S or M phase of the cell cycle. The histone fold domain of the C-terminal
      part of CENH3 is sufficient to target A. thaliana centromeres. A. thaliana EYFP
      CENH3 can recognize and target three different centromeric repeats of Arabidopsis
      lyrata but not field bean (Vicia faba) centromeres.

PMID- 17028206
TI  - A posttranslationally regulated protease, VheA, is involved in the liberation of
      juveniles from parental spheroids in Volvox carteri.
AB  - The lineage of volvocine algae includes unicellular Chlamydomonas and
      multicellular Volvox in addition to their colonial relatives intermediate in size
      and cell number. In an asexual life cycle, daughter cells of Chlamydomonas hatch
      from parental cell walls soon after cell division, while Volvox juveniles are
      released from parental spheroids after the completion of various developmental
      events required for the survival of multicellular juveniles. Thus, heterochronic
      change in the timing of hatching is considered to have played an important role
      in the evolution of multicellularity in volvocine algae. To study the hatching
      process in Volvox carteri, we purified a 125-kD Volvox hatching enzyme (VheA)
      from a culture medium with enzymatic activity to degrade the parental spheroids.
      The coding region of vheA contains a prodomain with a transmembrane segment, a
      subtilisin-like Ser protease domain, and a functionally unknown domain, although
      purified 125-kD VheA does not contain a prodomain. While 143-kD VheA with a
      prodomain is synthesized long before the hatching stage, 125-kD VheA is released
      into the culture medium during hatching due to cleavage processing at the site
      between the prodomain and the subtilisin-like Ser protease domain, indicating
      that posttranslational regulation is involved in the determination of the timing
      of hatching.

PMID- 17028207
TI  - Identification and characterization of components of a putative petunia S-locus F
      box-containing E3 ligase complex involved in S-RNase-based self-incompatibility.
AB  - Petunia inflata S-locus F-box (Pi SLF) is thought to function as a typical F-box
      protein in ubiquitin-mediated protein degradation and, along with Skp1, Cullin-1,
      and Rbx1, could compose an SCF complex mediating the degradation of nonself S
      RNase but not self S-RNase. We isolated three P. inflata Skp1s (Pi SK1, -2, and 
      3), two Cullin-1s (Pi CUL1-C and -G), and an Rbx1 (Pi RBX1) cDNAs and found that
      Pi CUL1-G did not interact with Pi RBX1 and that none of the three Pi SKs
      interacted with Pi SLF(2). We also isolated a RING-HC protein, S-RNase Binding
      Protein1 (Pi SBP1), almost identical to Petunia hybrida SBP1, which interacts
      with Pi SLFs, S-RNases, Pi CUL1-G, and an E2 ubiquitin-conjugating enzyme,
      suggesting that Pi CUL1-G, SBP1, and SLF may be components of a novel E3 ligase
      complex, with Pi SBP1 playing the roles of Skp1 and Rbx1. S-RNases interact more
      with nonself Pi SLFs than with self Pi SLFs, and Pi SLFs also interact more with
      nonself S-RNases than with self S-RNases. Bacterially expressed S(1)-, S(2)-, and
      S(3)-RNases are degraded by the 26S proteasomal pathway in a cell-free system,
      albeit not in an S-allele-specific manner. Native glycosylated S(3)-RNase is not
      degraded to any significant extent; however, deglycosylated S(3)-RNase is
      degraded as efficiently as the bacterially expressed S-RNases. Finally, S-RNases
      are ubiquitinated in pollen tube extracts, but whether this is mediated by the Pi
      SLF-containing E3 complex is unknown.

PMID- 17028208
TI  - Rice plastidial N-glycosylated nucleotide pyrophosphatase/phosphodiesterase is
      transported from the ER-golgi to the chloroplast through the secretory pathway.
AB  - A nucleotide pyrophosphatase/phosphodiesterase (NPP) activity that catalyzes the
      hydrolytic breakdown of ADP-glucose (ADPG) has been shown to occur in the
      plastidial compartment of both mono- and dicotyledonous plants. To learn more
      about this enzyme, we purified two NPPs from rice (Oryza sativa) and barley
      (Hordeum vulgare) seedlings. Both enzymes are glycosylated, since they bind to
      concanavalin A, stain with periodic acid-Schiff reagent, and are digested by Endo
      H. A complete rice NPP cDNA, designated as NPP1, was isolated, characterized, and
      overexpressed in transgenic plants displaying high ADPG hydrolytic activity.
      Databank searches revealed that NPP1 belongs to a functionally divergent group of
      plant nucleotide hydrolases. NPP1 contains numerous N-glycosylation sites and a
      cleavable hydrophobic signal sequence that does not match with the N-terminal
      part of the mature protein. Both immunocytochemical analyses and confocal
      fluorescence microscopy of rice cells expressing NPP1 fused with green
      fluorescent protein (GFP) revealed that NPP1-GFP occurs in the plastidial
      compartment. Brefeldin A treatment of NPP1-GFP-expressing cells prevented NPP1
      GFP accumulation in the chloroplasts. Endo-H digestibility studies revealed that
      both NPP1 and NPP1-GFP in the chloroplast are glycosylated. Collectively, these
      data demonstrate the trafficking of glycosylated proteins from the endoplasmic
      reticulum-Golgi system to the chloroplast in higher plants.

PMID- 17028209
TI  - Mutants of Arabidopsis lacking starch branching enzyme II substitute plastidial
      starch synthesis by cytoplasmic maltose accumulation.
AB  - Three genes, BE1, BE2, and BE3, which potentially encode isoforms of starch
      branching enzymes, have been found in the genome of Arabidopsis thaliana.
      Although no impact on starch structure was observed in null be1 mutants,
      modifications in amylopectin structure analogous to those of other branching
      enzyme II mutants were detected in be2 and be3. No impact on starch content was
      found in any of the single mutant lines. Moreover, three double mutant
      combinations were produced (be1 be2, be1 be3, and be2 be3), and the impact of the
      mutations on starch content and structure was analyzed. Our results suggest that
      BE1 has no apparent function for the synthesis of starch in the leaves, as both
      be1 be2 and be1 be3 double mutants display the same phenotype as be2 and be3
      separately. However, starch synthesis was abolished in be2 be3, while high levels
      of alpha-maltose were assayed in the cytosol. This result indicates that the
      functions of both BE2 and BE3, which belong to class II starch branching enzymes,
      are largely redundant in Arabidopsis. Moreover, we demonstrate that maltose
      accumulation depends on the presence of an active ADP-glucose pyrophosphorylase
      and that the cytosolic transglucosidase DISPROPORTIONATING ENZYME2, required for
      maltose metabolization, is specific for beta-maltose.

PMID- 17028210
TI  - Human immunodeficiency virus-infected patients with prior Pneumocystis pneumonia
      exhibit increased serologic reactivity to several major surface glycoprotein
      clones.
AB  - Recombinant clones of the carboxyl terminus of the major surface glycoprotein
      (MsgC) of Pneumocystis jirovecii are useful for analyzing serologic responses in
      humans. However, there is no standardized set of antigens in general use, which
      could lead to conflicting results. We have previously shown that human
      immunodeficiency virus type 1 (HIV-1)-infected patients with prior Pneumocystis
      pneumonia (PcP+) responded more frequently and more strongly to a clone of MsgC
      than did HIV-1-infected patients without PcP (PcP-). Here we test three new
      clones of MsgC to determine the effect of antigenic sequence variation on immune
      reactivity in blood donors and HIV-infected patients previously analyzed for
      reactivity to our original MsgC clone. In Western blot analyses, PcP+ patients
      exhibited the highest frequency of reactivity to each MsgC clone, and the
      frequency of reactivity with all four MsgC clones together was significantly
      higher in sera from PcP+ patients than in sera from the other patient groups.
      Furthermore, in an enzyme-linked immunosorbent assay we found that the PcP+
      population had the highest level of reactivity to two of the four clones tested.
      One of the new clones could distinguish between PcP+ and PcP- populations, and
      two MsgC clones could distinguish blood donors from the other patient
      populations. The results show that inherent differences in MsgC amino acid
      sequence can affect recognition by antibodies independently of variations in
      protein length or patient population, and the utility of a clone depends on its
      sequence and on the populations tested.

PMID- 17028211
TI  - Sequencing of the porB gene: a step toward a true characterization of Neisseria
      meningitidis.
AB  - Variations in class 2/3 (PorB) proteins form the basis for meningococcal
      serotyping. Antibodies against these proteins are bactericidal, making serotyping
      results useful not only for epidemiological surveillance of meningococcal disease
      but also for identifying potential vaccine components. A total of 20 to 60% of
      meningococcal B and C isolates from any given population are nontypeable (NT)
      using a panel of monoclonal antibodies. To analyze the mechanisms responsible for
      the nonserotypeability characteristic in Neisseria meningitidis, we (i)
      established the nucleotide sequences of porB gene in 146 meningococcal strains
      (95 not recognized by the serotyping panel), (ii) identified 18 new allelic
      variants of the porB gene, (iii) correlated allelic variants with serotypes, (iv)
      suggest the nontypeability characteristic in those 95 NT strains, and (v) reject
      the possibility of variation in the levels of PorB expression.

PMID- 17028212
TI  - Assessment of analysis of urinary pneumococcal antigen by immunochromatography
      for etiologic diagnosis of community-acquired pneumonia in adults.
AB  - The limitations of conventional microbiologic methods (CMM) for etiologic
      diagnosis of community pneumococcal pneumonia have made faster diagnostic
      techniques necessary. Our aim was to evaluate the usefulness of the
      immunochromatography (ICT) technique for detecting urinary Streptococcus
      pneumoniae antigen in the etiologic diagnosis of community-acquired pneumonias
      (CAP). This was a prospective study on in-patients with CAP in a tertiary
      hospital conducted from October 2000 to March 2004. Apart from using CMM to reach
      an etiologic diagnosis, we determined pneumococcal antigen in concentrated urine
      by ICT. We also determined the urinary pneumococcal antigen (UPA) content in
      patients from two control groups to calculate the specificity of the technique.
      One group was comprised of in-patients diagnosed with chronic obstructive
      pulmonary disease (COPD) or asthma, with respiratory infection, and without
      pneumonia; the other group included fractures. We studied 959 pneumonia patients
      and determined UPA content in 911 (95%) of them. We diagnosed the etiology of 253
      cases (28%) using CMM; S. pneumoniae was the most common etiologic agent (57
      cases). ICT analysis was positive for 279 patients (31%). Using this technique,
      the percentage of diagnoses of pneumococcal pneumonias increased by 26%, while
      the overall etiologic diagnosis increased from 28 to 49%. The technique
      sensitivity was 81%; the specificity oscillated between 80% in CAP with
      nonpneumococcal etiology and 99% for patients with fractures without infections.
      Determination of UPA is a rapid, simple analysis with good sensitivity and
      specificity, which increased the percentage of etiologic diagnoses. Positive UPA
      may persist in COPD patients with probable pneumococcal colonization or recent
      pneumococcal infections.

PMID- 17028213
TI  - Immune responses of elk to initial and booster vaccinations with Brucella abortus
      strain RB51 or 19.
AB  - Previous studies have suggested that currently available brucellosis vaccines
      induce poor or no protection in elk (Cervus elaphus nelsoni). In this study, we
      characterized the immunologic responses of elk after initial or booster
      vaccination with Brucella abortus strains RB51 (SRB51) and 19 (S19). Elk were
      vaccinated with saline or 10(10) CFU of SRB51 or S19 (n=seven animals/treatment)
      and booster vaccinated with a similar dosage of the autologous vaccine at 65
      weeks. Compared to nonvaccinates, elk vaccinated with SRB51 or S19 had greater
      (P<0.05) antibody responses to SRB51 or S19 after initial vaccination and after
      booster vaccination. Compared to nonvaccinated elk, greater (P<0.05)
      proliferative responses to autologous antigen after initial vaccination occurred
      at only a few sample times in SRB51 (6, 14, and 22 weeks) and S19 (22 weeks)
      treatment groups. In general, proliferative responses of vaccinates to
      nonautologous antigens did not differ (P>0.05) from the responses of
      nonvaccinated elk. Gamma interferon production in response to autologous or
      nonautologous Brucella antigens did not differ (P>0.05) between controls and
      vaccinates after booster vaccination. Flow cytometric techniques suggested that
      proliferation occurred more frequently in immunoglobulin M-positive cells, with
      differences between vaccination and control treatments in CD4+ and CD8+ subset
      proliferation detected only at 22 weeks after initial vaccination. After booster
      vaccination, one technique ([3H]thymidine incorporation) suggested that
      proliferative responses to SRB51 antigen, but not S19 antigen, were greater
      (P<0.05) in vaccinates compared to the responses of nonvaccinates. However, in
      general, flow cytometric and other techniques failed to detect significant
      anamnestic responses to autologous or nonautologous Brucella antigens in S19 or
      SRB51 vaccinates after booster vaccination. Although some cellular immune
      responses were detected after initial or booster vaccination of elk with SRB51 or
      S19, our data suggest that responses tend to be transient and much less robust
      than previously reported in SRB51-vaccinated cattle (Bos taurus) or bison (Bison
      bison). These data may explain why the vaccination of elk with S19 and SRB51
      induces poor protection against brucellosis.

PMID- 17028214
TI  - Amastin peptide-binding antibodies as biomarkers of active human visceral
      leishmaniasis.
AB  - Amastin surface proteins belong to a large family of developmentally regulated
      proteins comprising up to 45 members that have recently been discovered in the
      genus Leishmania and are highly similar to the amastin proteins in Trypanosoma
      cruzi. All members of the amastin gene family contain a highly conserved 11-amino
      acid (aa) signature at the N terminus, which is unique to the amastin proteins
      and to the Trypanosomatidae family. Recent studies have demonstrated that this
      region is highly protective in a mouse model. The goal of the present study was
      to evaluate the potential of the 50-aa N-terminal domain of amastin proteins
      harboring the conserved 11-aa amastin signature peptide as a relevant immune
      biomarker of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). We
      report here the amastin-binding total immunoglobulins (IgG) and/or IgG subclasses
      in the sera of patients at different stages of CL (n=90) and VL (n=41). In CL
      cases, there is no significant difference in seroreactivities between active,
      recovered, and nonhealed cases. However, the amastin peptide-reactive antibodies
      were present at high titers in 19 of 20 sera collected from patients with active
      VL compared to sera from patients recovered from VL and asymptomatic cases of VL.
      These data suggest that the amastin signature peptide could represent a relevant
      biomarker for the serodiagnosis of VL and, most importantly, that it could permit
      differentiation among the different stages of the disease.

PMID- 17028215
TI  - Induction of long-term lipopolysaccharide tolerance by an agonistic monoclonal
      antibody to the toll-like receptor 4/MD-2 complex.
AB  - We have established an agonistic monoclonal antibody, UT12, that induces
      stimulatory signals comparable to those induced by lipopolysaccharide (LPS)
      through Toll-like receptor 4 and MD-2. UT12 activated nuclear factor kappaB and
      induced the production of proinflammatory cytokines such as tumor necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) in peritoneal exudative cells. In
      addition, mice injected with UT12 rapidly fell into endotoxin shock concomitant
      with the augmentation of serum TNF-alpha and IL-6 levels, followed by death
      within 12 h. On the other hand, when the mice were pretreated with a sublethal
      dose of UT12, the mice survived the subsequent lethal LPS challenges, with
      significant suppression of serum TNF-alpha and IL-6, indicating that UT12 induced
      tolerance against LPS. This effect of UT12 was maintained for at least 9 days. In
      contrast, the tolerance induced by LPS continued for less than 3 days. These
      results illuminate a novel potential therapeutic strategy for endotoxin shock by
      the use of monoclonal antibodies against the Toll-like receptor 4/MD-2 complex.

PMID- 17028216
TI  - Identification and characterization of a major cell wall-associated iron
      regulated envelope protein (Irep-28) in Mycobacterium tuberculosis.
AB  - Iron limitation and the expression of mycobactin and carboxymycobactin by
      Mycobacterium tuberculosis are known. Here, we report how iron regulated the
      coordinate expression of these two siderophores and a 28-kDa cell wall-associated
      iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU
      homologue HupB protein (hupB [Rv2986c]). Antibodies to this protein were detected
      in sera from tuberculosis patients. The location of the protein in the cell wall
      makes it a potential drug target.

PMID- 17028217
TI  - Comparison of the proteosomes and antigenicities of secreted and cellular
      proteins produced by Mycobacterium paratuberculosis.
AB  - The protein expression profiles and antigenicities of both culture filtrates (CF)
      and cellular extracts (CE) of Mycobacterium paratuberculosis were compared by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), one
      dimensional electrophoresis (1-DE) and 2-DE immunoblotting, and enzyme-linked
      immunosorbent assay (ELISA). The CF proteins were harvested from supernatants of
      stationary-phase liquid cultures and concentrated by size exclusion filtration.
      The CE proteins were extracted by mechanical disruption of cells using glass
      beads and a high-speed agitator. Analysis of SDS-PAGE gels showed that the
      majority of CF proteins had low molecular masses (<50 kDa), whereas CE protein
      mass ranged more evenly over a broader range up to 100 kDa. By 2-DE, CF proteins
      had a narrow array of pI values, with most being between pH 4.0 and 5.5; CE
      proteins spanned pI values from pH 4.0 to 7.0. The antigenicities of CF and CE
      proteins were first determined by 1-DE and 2-DE immunoblotting with serum from a
      cow naturally infected with M. paratuberculosis. The serum reacted strongly to
      more proteins in the CF than the CE. Sera from 444 infected and 412 uninfected
      cattle were tested by ELISA with CF and CE as solid-phase antigens. Receiver
      operator characteristic curve analysis of the ELISA results showed a
      significantly greater area under the curve for CF compared to CE (P<0.05). A high
      degree of variability in protein binding patterns was shown with 1-DE immunoblot
      analysis with 31 sera from M. paratuberculosis-infected cattle. Collectively,
      these results indicate that serologic tests for bovine paratuberculosis may be
      improved by using proteins derived from CF instead of CE. To maximize the
      diagnostic sensitivity of serologic tests, multiple proteins will be required.
      Even so, a CF ELISA may not be able to detect all M. paratuberculosis-infected
      cattle, in particular those in the early stages of infection that have yet to
      mount an antibody response.

PMID- 17028218
TI  - Analysis of antibody response in humans to the type A OspC loop 5 domain and
      assessment of the potential utility of the loop 5 epitope in Lyme disease vaccine
      development.
AB  - The OspC protein of Borrelia burgdorferi is an immunodominant antigen. Here we
      demonstrate that the loop 5 domain of type A OspC is surface exposed, elicits
      bactericidal antibody in mice, and is antigenic in humans. The data suggest that
      loop 5 may be suitable for inclusion in a polyvalent, chimeric OspC vaccinogen.

PMID- 17028219
TI  - Limited diagnostic capacities of two commercial assays for the detection of
      Leptospira immunoglobulin M antibodies in Laos.
AB  - The diagnostic utility of immunochromatographic (Leptotek) and enzyme-linked
      immunosorbent assay (ELISA; Panbio) tests for the detection of Leptospira
      immunoglobulin M antibodies was assessed in febrile adults admitted in Vientiane,
      Laos. Both tests demonstrated poor diagnostic accuracy using admission serum
      (Leptotek sensitivity of 47.3% and specificity of 75.5%: ELISA sensitivity of
      60.9% and specificity of 65.6%) compared to the Leptospira "gold standard"
      microscopic agglutination test.

PMID- 17028221
TI  - Cell-mediated immune responses to smallpox vaccination.
AB  - We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus
      vaccination status had no significant effect on cell-mediated immune responses
      (i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell
      response measured by enzyme-linked immunospot assay) 1 month after smallpox
      vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).

PMID- 17028220
TI  - Serologic evaluation of patients from Missouri with erythema migrans-like skin
      lesions with the C6 Lyme test.
AB  - Southern tick-associated rash illness (STARI), also known as Masters disease,
      affects people predominantly in the Southeast and South Central United States.
      These patients exhibit skin lesions that resemble erythema migrans (EM), the
      characteristic skin lesion in early Lyme disease. The etiology of STARI remains
      unknown, and no serologic test is available to aid in its diagnosis. The C6 Lyme
      enzyme-linked immunosorbent assay was used to evaluate coded serum specimens from
      patients with STARI at two laboratory sites. The specimens tested at one site
      consisted of acute- and convalescent-phase samples that were obtained from nine
      STARI patients from Missouri and from one patient with documented Borrelia
      lonestari infection who acquired this infection in either North Carolina or
      Maryland. All of these samples were C6 negative. Seventy acute- or convalescent
      phase specimens from 63 STARI patients from Missouri were C6 tested at the second
      site. All but one of these STARI specimens were also negative. In contrast, of
      nine acute- and nine convalescent-phase serum specimens obtained from culture
      confirmed Lyme disease patients with EM from New York state, seven were C6
      positive at the acute stage, and eight were positive at convalescence. The C6
      test is negative in patients with STARI, providing further evidence that B.
      burgdorferi is not the etiologic agent of this disease.

PMID- 17028222
TI  - High levels of serum thromboxane B2 are generated during human pulmonary
      dirofilariosis.
AB  - The canine parasite Dirofilaria immitis can infect humans. Patients with
      pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than
      healthy individuals living in areas where dirofilariosis is endemic and in areas
      where dirofilariosis is not endemic. The possible role of Wolbachia bacteria in
      the appearance of this eicosanoid is discussed.

PMID- 17028223
TI  - Change in substrate preference of Streptomyces aminopeptidase through
      modification of the environment around the substrate binding site.
AB  - We attempted to alter the substrate preference of aminopeptidase from
      Streptomyces septatus TH-2 (SSAP). Because Asp198 and Phe221 of SSAP are located
      in the substrate binding site, we screened 2,000 mutant enzymes with D198X/F221X
      mutations. By carrying out this examination, we obtained two enzymes; one
      specifically hydrolyzed an arginyl derivative, and the other specifically
      hydrolyzed a cystinyl derivative (65- and 12.5-fold higher k(cat) values for
      hydrolysis of p-nitroanilide derivatives than those of the wild type,
      respectively).

PMID- 17028224
TI  - Studies of the extracellular glycocalyx of the anaerobic cellulolytic bacterium
      Ruminococcus albus 7.
AB  - Anaerobic cellulolytic bacteria are thought to adhere to cellulose via several
      mechanisms, including production of a glycocalyx containing extracellular
      polymeric substances (EPS). As the compositions and structures of these
      glycocalyces have not been elucidated, variable-pressure scanning electron
      microscopy (VP-SEM) and chemical analysis were used to characterize the
      glycocalyx of the ruminal bacterium Ruminococcus albus strain 7. VP-SEM revealed
      that growth of this strain was accompanied by the formation of thin cellular
      extensions that allowed the bacterium to adhere to cellulose, followed by
      formation of a ramifying network that interconnected individual cells to one
      another and to the unraveling cellulose microfibrils. Extraction of 48-h-old
      whole-culture pellets (bacterial cells plus glycocalyx [G] plus residual
      cellulose [C]) with 0.1 N NaOH released carbohydrate and protein in a ratio of
      1:5. Boiling of the cellulose fermentation residue in a neutral detergent
      solution removed almost all of the adherent cells and protein while retaining a
      residual network of adhering noncellular material. Trifluoroacetic acid
      hydrolysis of this residue (G plus C) released primarily glucose, along with
      substantial amounts of xylose and mannose, but only traces of galactose, the most
      abundant sugar in most characterized bacterial exopolysaccharides. Linkage
      analysis and characterization by nuclear magnetic resonance suggested that most
      of the glucosyl units were not present as partially degraded cellulose.
      Calculations suggested that the energy demand for synthesis of the nonprotein
      fraction of EPS by this organism represents only a small fraction (<4%) of the
      anabolic ATP expenditure of the bacterium.

PMID- 17028225
TI  - Quantification and stability of human adenoviruses and polyomavirus JCPyV in
      wastewater matrices.
AB  - Human adenoviruses (HAdV) and human polyomavirus JCPyV have been previously
      proposed as indicators of fecal viral contamination in the environment. Different
      wastewater matrices have been analyzed by applying real-time quantitative PCR
      procedures for the presence, quantity, and stability of a wide diversity of
      excreted HAdV and JCPyV. High quantities of HAdV and JCPyV were detected in
      sewage, effluent wastewater, sludge, and biosolid samples. Both viruses showed
      high stability in urban sewage. These results confirm the suitability of both
      viruses as indicators of human fecal viral pollution.

PMID- 17028226
TI  - Diversity and significance of mold species in Norwegian drinking water.
AB  - In order to determine the occurrence, distribution, and significance of mold
      species in groundwater- and surface water-derived drinking water in Norway, molds
      isolated from 273 water samples were identified. Samples of raw water, treated
      water, and water from private homes and hospital installations were analyzed by
      incubation of 100-ml membrane-filtered samples on dichloran-18% glycerol agar.
      The total count (number of CFU per 100 ml) of fungal species and the species
      diversity within each sample were determined. The identification of mold species
      was based on morphological and molecular methods. In total, 94 mold species
      belonging to 30 genera were identified. The mycobiota was dominated by species of
      Penicillium, Trichoderma, and Aspergillus, with some of them occurring throughout
      the drinking water system. Several of the same species as isolated from water may
      have the potential to cause allergic reactions or disease in humans. Other
      species are common contaminants of food and beverages, and some may cause
      unwanted changes in the taste or smell of water. The present results indicate
      that the mycobiota of water should be considered when the microbiological safety
      and quality of drinking water are assessed. In fact, molds in drinking water
      should possibly be included in the Norwegian water supply and drinking water
      regulations.

PMID- 17028227
TI  - Longitudinal analysis of tick densities and Borrelia, Anaplasma, and Ehrlichia
      infections of Ixodes ricinus ticks in different habitat areas in The Netherlands.
AB  - From 2000 to 2004, ticks were collected by dragging a blanket in four habitat
      areas in The Netherlands: dunes, heather, forest, and a city park. Tick densities
      were calculated, and infection with Borrelia burgdorferi and Anaplasma and
      Ehrlichia species was investigated by reverse line blot analysis. The lowest tick
      density was observed in the heather area (1 to 8/100 m2). In the oak forest and
      city park, the tick densities ranged from 26 to 45/100 m2. The highest tick
      density was found in the dune area (139 to 551/100 m2). The infection rates
      varied significantly for the four study areas and years, ranging from 0.8 to 11.
      5% for Borrelia spp. and 1 to 16% for Ehrlichia or Anaplasma
      (Ehrlichia/Anaplasma) spp. Borrelia infection rates were highest in the dunes,
      followed by the forest, the city park, and heather area. In contrast,
      Ehrlichia/Anaplasma was found most often in the forest and less often in the city
      park. The following Borrelia species were found: Borrelia sensu lato strains not
      identified to the species level (2.5%), B. afzelii (2.5%), B. valaisiana (0.9%),
      B. burgdorferi sensu stricto (0.13%), and B. garinii (0.13%). For
      Ehrlichia/Anaplasma species, Ehrlichia and Anaplasma spp. not identified to the
      species level (2.5%), Anaplasma schotti variant (3.5%), Anaplasma phagocytophilum
      variant (0.3%), and Ehrlichia canis (0.19%) were found. E. canis is reported for
      the first time in ticks in The Netherlands in this study. Borrelia lusitaniae,
      Ehrlichia chaffeensis, and the human granylocytic anaplasmosis agent were not
      detected. About 1.6% of the ticks were infected with both Borrelia and
      Ehrlichia/Anaplasma, which was higher than the frequency predicted from the
      individual infection rates, suggesting hosts with multiple infections or a
      possible selective advantage of coinfection.

PMID- 17028228
TI  - A yeast platform for the production of single-chain antibody-green fluorescent
      protein fusions.
AB  - Fusion proteins comprised of a binding domain and green fluorescent protein (GFP)
      have the potential to act as one-step binding reagents. In this study, eight
      single-chain antibodies (scFv) and one single-chain T-cell receptor (scTCR) were
      secreted as fusions to GFP using a Saccharomyces cerevisiae expression system.
      Fusion protein secretion levels ranged over 3 orders of magnitude, from 4
      microg/liter to 4 mg/liter, and correlated well with the secretion levels of the
      unfused scFv/scTCR. Three fusion types with various linker lengths and fusion
      orientations were tested for each scFv/scTCR. Although the fusion protein
      secretion levels were not significantly affected by the nature of the fusion
      construct, the properties of the fusion protein were clearly influenced. The
      fluorescence yield per fusion molecule was increased by separating the scFv/scTCR
      and GFP with an extended (GGGGS)3 linker, and fusions with scFv/scTCR at the
      carboxy-terminus were more resistant to degradation. By evaluating leader
      sequence processing and using GFP fluorescence to track intracellular processing,
      it was determined that the majority of fusion protein synthesized by the yeast
      was not secreted and in most cases was accumulating in an immature, although
      active, endoplasmic-reticulum (ER)-processed form. This contrasted with unfused
      scFv, which accumulated in both immature ER-processed and mature post-Golgi
      forms. The results indicated that yeast can be used as an effective host for the
      secretion of scFv/scTCR-GFP fusion proteins and that as a result of intracellular
      secretory bottlenecks, there is considerable yeast secretory capacity remaining
      to be exploited.

PMID- 17028229
TI  - Can Anopheles gambiae be infected with Wolbachia pipientis? Insights from an in
      vitro system.
AB  - Wolbachia pipientis are maternally inherited endosymbionts associated with
      cytoplasmic incompatibility, a potential mechanism to drive transgenic traits
      into Anopheles populations for malaria control. W. pipientis infections are
      common in many mosquito genera but have never been observed in any Anopheles
      species, leading to the hypothesis that Anopheles mosquitoes are incapable of
      harboring infection. We used an in vitro system to evaluate the ability of
      Anopheles gambiae cells to harbor diverse W. pipientis infections. We
      successfully established W. pipientis infections (strains wRi and wAlbB) in the
      immunocompetent Anopheles gambiae cell line Sua5B. Infection was confirmed by
      PCR, antibiotic curing, DNA sequencing, and direct observation using fluorescence
      in situ hybridization. The infections were maintained at high passage rates for
      >30 passages. Our results indicate that there is no intrinsic genetic block to W.
      pipientis infection in A. gambiae cells, suggesting that establishment of in vivo
      W. pipientis infections in Anopheles mosquitoes may be feasible.

PMID- 17028230
TI  - Isolation and molecular characterization of chitinase-deficient Bacillus
      licheniformis strains capable of deproteinization of shrimp shell waste to obtain
      highly viscous chitin.
AB  - Proteolytic but chitinase-deficient microbial cultures were isolated from shrimp
      shell waste and characterized. The most efficient isolate was found to be a mixed
      culture consisting of two Bacillus licheniformis strains, which were first
      determined microscopically and physiologically. Molecular characterization was
      carried out by sequencing the 16S rRNA gene of both strains. According to the
      residual protein and ash content, the chitin obtained by fermentation of such a
      mixed culture was found to be comparable to a commercially available, chemically
      processed product. However, the strikingly high viscosity (80 versus 10 mPa of
      the commercially available sample) indicates its superior quality. The two
      strains differed in colony morphology and in their secretion capabilities for
      degradative extracellular enzymes. Sequencing of the loci encoding amylase,
      cellulase, chitinases, and proteases, as well as the degS/degU operon, which is
      instrumental in the regulation of degradative enzymes, and the pga operon, which
      is responsible for polyglutamic acid production, revealed no differences.
      However, a frameshift mutation in chiA, encoding a chitinase, was validated for
      both strains, providing an explanation for the ascertained absence of
      chitinolytic activities and the concomitant possibility of producing highly
      viscous chitin in a fermentational deproteinization process.

PMID- 17028232
TI  - Rainfall-induced release of fecal coliforms and other manure constituents:
      comparison and modeling.
AB  - Modeling release of fecal coliforms is an important component of fate and
      transport simulations related to environmental water quality. Manure constituents
      other than fecal coliforms may serve as natural tracers of fecal contamination
      provided that their release from manure to runoff is similar to the fecal
      coliform release. The objectives of this work were to compare release of fecal
      coliforms (FC), chloride (Cl-), organic carbon (OC), and water-soluble phosphorus
      (P) from dissolving manure and to assess the performance of three models in
      describing the observed release. Bovine manure was applied on 0.5- by 0.3-m bare
      and vegetated subplots with 20% slope on sandy loam and clay loam soils.
      Concentrations of Cl-, FC, OC, and P were measured in runoff collected from
      troughs at the edges of the subplots at 5-min intervals during 1-h rainfall
      simulations. The one-parametric exponential model and two-parametric Vadas
      Kleinman-Sharpley model and Bradford-Schijven model were fitted to the data. The
      Bradford-Schijven model had uncorrelated parameters, one of which was linearly
      related to the irrigation rate, and another parameter reflected the presence or
      the absence of vegetation. Kinetics of the FC release from manure was similar to
      the release kinetics of P and OC. The Bradford-Schijven model is recommended to
      simulate the release of manure constituents.

PMID- 17028231
TI  - Escherichia coli biofilms formed under low-shear modeled microgravity in a ground
      based system.
AB  - Bacterial biofilms cause chronic diseases that are difficult to control. Since
      biofilm formation in space is well documented and planktonic cells become more
      resistant and virulent under modeled microgravity, it is important to determine
      the effect of this gravity condition on biofilms. Inclusion of glass microcarrier
      beads of appropriate dimensions and density with medium and inoculum, in vessels
      specially designed to permit ground-based investigations into aspects of low
      shear modeled microgravity (LSMMG), facilitated these studies. Mathematical
      modeling of microcarrier behavior based on experimental conditions demonstrated
      that they satisfied the criteria for LSMMG conditions. Experimental observations
      confirmed that the microcarrier trajectory in the LSMMG vessel concurred with the
      predicted model. At 24 h, the LSMMG Escherichia coli biofilms were thicker than
      their normal-gravity counterparts and exhibited increased resistance to the
      general stressors salt and ethanol and to two antibiotics (penicillin and
      chloramphenicol). Biofilms of a mutant of E. coli, deficient in sigma(s), were
      impaired in developing LSMMG-conferred resistance to the general stressors but
      not to the antibiotics, indicating two separate pathways of LSMMG-conferred
      resistance.

PMID- 17028233
TI  - Evidence for the ubiquity of mixotrophic bacteria in the upper ocean:
      implications and consequences.

PMID- 17028234
TI  - Identification of novel Cryptosporidium genotypes from avian hosts.
AB  - A total of 430 avian-derived fecal specimens were randomly collected from
      selected Western Australian commercial aviaries, poultry farms, hatcheries,
      wildlife parks, and the Perth Zoo and screened for the presence of
      Cryptosporidium by PCR. Of these, 27 Cryptosporidium-positive isolates were
      detected, characterized, and compared with 11 avian-derived isolates from the
      Czech Republic at the 18S rRNA and actin gene loci. Sequence and phylogenetic
      analysis identified four genetically distinct genotypes, avian genotypes I to IV,
      from various avian hosts. In addition, the host range for Cryptosporidium galli
      was extended. Cryptosporidium muris and Cryptosporidium andersoni were also
      identified in a tawny frogmouth and a quail-crested wood partridge, respectively.

PMID- 17028235
TI  - Identification of a putative operon involved in fructooligosaccharide utilization
      by Lactobacillus paracasei.
AB  - The growth and activity of some Lactobacillus and Bifidobacterium strains are
      stimulated by the presence of nondigestible fructooligosaccharides (FOS), which
      are selectively fermented by specific intestinal bacteria. Consumption of FOS,
      therefore, enriches for those bacteria that possess metabolic pathways necessary
      for FOS metabolism. In this study, a DNA microarray consisting of 7,680 random
      genomic library fragments of Lactobacillus paracasei 1195 was used to examine
      genes involved in the utilization of FOS in this organism. Differential
      expression profiles between cells grown on FOS and those grown on glucose
      provided a basis for identifying genes specifically induced by FOS. Several of
      the FOS-induced genes shared sequence identity with genes encoding beta
      fructosidases and components of phosphoenolpyruvate-dependent phosphotransferase
      systems (PTS). These genes were organized in a putative operon, designated the
      fos operon, that may play an essential role in FOS utilization. The complete
      7,631-bp nucleotide sequence of the putative fos operon was determined and
      consists of fosABCDXE genes, which encode a putative fructose/mannose PTS
      (FosABCDX) and a beta-fructosidase precursor (FosE). The latter contains an N
      terminal signal peptide sequence and cell wall sorting signals at the C-terminal
      region, suggesting its localization at the cell wall. Inactivation of the fosE
      gene led to impaired growth on FOS and other beta-fructose-linked carbohydrates.
      Transcriptional analysis by reverse transcriptase PCR suggested that fosABCDXE
      was cotranscribed as a single mRNA during growth on FOS. Expression array
      analysis revealed that when glucose was added to FOS-grown cells, transcription
      of the FOS-induced genes was repressed, indicating that FOS metabolism is subject
      to catabolite regulation.

PMID- 17028236
TI  - Multilocus sequence typing supports the hypothesis that cow- and human-associated
      Salmonella isolates represent distinct and overlapping populations.
AB  - A collection of 179 human and 156 bovine clinical Salmonella isolates obtained
      from across New York state over the course of 1 year was characterized using
      serotyping and a multilocus sequence typing (MLST) scheme based on the sequencing
      of three genes (fimA, manB, and mdh). The 335 isolates were differentiated into
      52 serotypes and 72 sequence types (STs). Analyses of bovine isolates collected
      on different farms over time indicated that specific subtypes can persist over
      time on a given farm; in particular, a number of farms showed evidence for the
      persistence of a specific Salmonella enterica serotype Newport sequence type.
      Serotypes and STs were not randomly distributed among human and bovine isolates,
      and selected serotypes and STs were associated exclusively with either human or
      bovine sources. A number of common STs were geographically widespread. For
      example, ST6, which includes isolates representing serotype Typhimurium as well
      as the emerging serotype 4,5,12:i:-, was found among human and bovine isolates in
      a number of counties in New York state. Phylogenetic analyses supported the
      possibility that serotype 4,5,12:i:- is closely related to Salmonella serotype
      Typhimurium. Salmonella serotype Newport was found to represent two distinct
      evolutionary lineages that differ in their frequencies among human and bovine
      isolates. A number of Salmonella isolates carried two copies of manB (33
      isolates) or showed small deletion events in fimA (nine isolates); these
      duplication and deletion events may provide mechanisms for the rapid
      diversification of Salmonella surface molecules. We conclude that the combined
      use of an economical three-gene MLST scheme and serotyping can provide
      considerable new insights into the evolution and transmission of Salmonella.

PMID- 17028237
TI  - Molecular detection of epiphytic Acaryochloris spp. on marine macroalgae.
AB  - A molecular method for detecting the epiphyte community on marine macroalgae was
      developed by using PCR-denaturing gradient gel electrophoresis. Selective
      amplification of 16S rRNA gene fragments from either cyanobacteria or algal
      plastids improved the detection of minor epiphytes. Two phylotypes of
      Acaryochloris, a chlorophyll d-containing cyanobacterium, were found not only on
      red macroalgae but also on green and brown macroalgae.

PMID- 17028238
TI  - Bacterial community structure in the hyperarid core of the Atacama Desert, Chile.
AB  - Soils from the hyperarid Atacama Desert of northern Chile were sampled along an
      east-west elevational transect (23.75 to 24.70 degrees S) through the driest
      sector to compare the relative structure of bacterial communities. Analysis of
      denaturing gradient gel electrophoresis (DGGE) profiles from each of the samples
      revealed that microbial communities from the extreme hyperarid core of the desert
      clustered separately from all of the remaining communities. Bands sequenced from
      DGGE profiles of two samples taken at a 22-month interval from this core region
      revealed the presence of similar populations dominated by bacteria from the
      Gemmatimonadetes and Planctomycetes phyla.

PMID- 17028239
TI  - Intracellular accumulation of trehalose protects Lactococcus lactis from freeze
      drying damage and bile toxicity and increases gastric acid resistance.
AB  - Interleukin-10 (IL-10) is a promising candidate for the treatment of inflammatory
      bowel disease. Intragastric administration of Lactococcus lactis genetically
      modified to secrete IL-10 in situ in the intestine was shown to be effective in
      healing and preventing chronic colitis in mice. However, its use in humans is
      hindered by the sensitivity of L. lactis to freeze-drying and its poor survival
      in the gastrointestinal tract. We expressed the trehalose synthesizing genes from
      Escherichia coli under control of the nisin-inducible promoter in L. lactis.
      Induced cells accumulated intracellular trehalose and retained nearly 100%
      viability after freeze-drying, together with a markedly prolonged shelf life.
      Remarkably, cells producing trehalose were resistant to bile, and their viability
      in human gastric juice was enhanced. None of these effects were seen with
      exogenously added trehalose. Trehalose accumulation did not interfere with IL-10
      secretion or with therapeutic efficacy in murine colitis. The newly acquired
      properties should enable a larger proportion of the administered bacteria to
      reach the gastrointestinal tract in a bioactive form, providing a means for more
      effective mucosal delivery of therapeutics.

PMID- 17028241
TI  - Activity of a second Trypanosoma brucei hexokinase is controlled by an 18-amino
      acid C-terminal tail.
AB  - Trypanosoma brucei expresses two hexokinases that are 98% identical, namely,
      TbHK1 and TbHK2. Homozygous null TbHK2-/- procyclic-form parasites exhibit an
      increased doubling time, a change in cell morphology, and, surprisingly, a
      twofold increase in cellular hexokinase activity. Recombinant TbHK1 enzymatic
      activity is similar to that of other hexokinases, with apparent Km values for
      glucose and ATP of 0.09 +/- 0.02 mM and 0.28 +/- 0.1 mM, respectively. The k(cat)
      value for TbHK1 is 2.9 x 10(4) min(-1). TbHK1 can use mannose, fructose, 2
      deoxyglucose, and glucosamine as substrates. In addition, TbHK1 is inhibited by
      fatty acids, with lauric, myristic, and palmitic acids being the most potent
      (with 50% inhibitory concentrations of 75.8, 78.4, and 62.4 microM,
      respectively). In contrast to TbHK1, recombinant TbHK2 lacks detectable enzymatic
      activity. Seven of the 10 amino acid differences between TbHK1 and TbHK2 lie
      within the C-terminal 18 amino acids of the polypeptides. Modeling of the
      proteins maps the C-terminal tails near the interdomain cleft of the enzyme that
      participates in the conformational change of the enzyme upon substrate binding.
      Replacing the last 18 amino acids of TbHK2 with the corresponding residues of
      TbHK1 yields an active recombinant protein with kinetic properties similar to
      those of TbHK1. Conversely, replacing the C-terminal tail of TbHK1 with the TbHK2
      tail inactivates the enzyme. These findings suggest that the C-terminal tail of
      TbHK1 is important for hexokinase activity. The altered C-terminal tail of TbHK2,
      along with the phenotype of the knockout parasites, suggests a distinct function
      for the protein.

PMID- 17028242
TI  - The illness trajectory of elderly cancer patients across cultures: SIOG position
      paper.
AB  - BACKGROUND: Due to the aging of the population, cancer has become a health
      priority worldwide. While the number of elderly cancer patients is rapidly
      increasing, many barriers still exist to their effective management. Compared
      with their younger counterparts, the elderly are less likely to receive optimal
      medical, psychological and spiritual treatment provided in a culturally competent
      manner. DESIGN: The scanty literature on cultural competence in elderly cancer
      patients has been reviewed. Additional material has been selected based on the
      authors' clinical research in medical oncology and psycho-oncology, and on their
      scholarly work in anthropology and bioethics. RESULTS: The aging process is a
      synergistic product of biological, behavioral and social issues within a cultural
      context. Knowledge about how older people understand, perceive and experience
      their illness trajectory and make choices is essential to the planning and
      delivering of effective cancer care. CONCLUSION: This position paper of the SIOG
      Task Force on Cultural Competence in the Elderly creates awareness of the
      influence of culture in geriatric oncology. Negotiating cross-cultural issues in
      geriatric oncology helps managing possible conflicts between patients, families
      and physicians over differing health care values, beliefs, or practices. Possible
      areas of future scholarly investigation and clinical research are identified.

PMID- 17028240
TI  - Reciprocal nuclear shuttling of two antagonizing Zn finger proteins modulates Tup
      family corepressor function to repress chromatin remodeling.
AB  - The Schizosaccharomyces pombe global corepressors Tup11 and Tup12, which are
      orthologs of Saccharomyces cerevisiae Tup1, are involved in glucose-dependent
      transcriptional repression and chromatin alteration of the fbp1+ gene. The fbp1+
      promoter contains two regulatory elements, UAS1 and UAS2, one of which (UAS2)
      serves as a binding site for two antagonizing C2H2 Zn finger transcription
      factors, the Rst2 activator and the Scr1 repressor. In this study, we analyzed
      the role of Tup proteins and Scr1 in chromatin remodeling at fbp1+ during glucose
      repression. We found that Scr1, cooperating with Tup11 and Tup12, functions to
      maintain the chromatin of the fbp1+ promoter in a transcriptionally inactive
      state under glucose-rich conditions. Consistent with this notion, Scr1 is quickly
      exported from the nucleus to the cytoplasm at the initial stage of derepression,
      immediately after glucose starvation, at which time Rst2 is known to be imported
      into the nucleus. In addition, chromatin immunoprecipitation assays revealed a
      switching of Scr1 to Rst2 bound at UAS2 during glucose derepression. On the other
      hand, Tup11 and Tup12 persist in the nucleus and bind to the fbp1+ promoter under
      both derepressed and repressed conditions. These observations suggest that Tup1
      like proteins recruited to the fbp1+ promoter are controlled by either of two
      antagonizing C2H2 Zn finger proteins. We propose that the actions of Tup11 and
      Tup12 are regulated by reciprocal nuclear shuttling of the two antagonizing Zn
      finger proteins in response to the extracellular glucose concentration. This
      notion provides new insights into the molecular mechanisms of the Tup family
      corepressors in gene regulation.

PMID- 17028243
TI  - Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years)
      women with metastatic breast cancer? Early interruption of a phase II study.
AB  - BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer
      with moderate toxicity, in 2002 we started a phase II trial with a combination
      regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus
      partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus
      gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with
      advanced breast cancer and measurable lesions. All patients underwent
      multidimensional geriatric assessment before enrollment. A two-step design was
      applied, and the trial would be completed if an overall response rate>or=30% was
      obtained with a grade 3-grade 4 (G3-G4) toxicity rate<or=25% (excluding
      neutropenia) in the first step. RESULTS: Twelve eligible patients had a median
      age of 74 years. At MGA, eight patients were fit, three vulnerable, one frail due
      to major depression; only two patients had G3 comorbidities according to
      Cumulative Illness Rating Scale-Geriatric. Seventy-five percent of patients had
      visceral disease. We obtained only one partial remission (11.1%) and six
      stabilizations of disease in nine assessable patients, with a time to progression
      of 3 months. Three patients (25%) experienced G3 neutropenia, and three patients
      (25%) developed G3 anemia (one patient) and G3 gastrointestinal toxicity (two
      patients). CONCLUSIONS: The promising response rates obtained with this
      combination by other authors could not be confirmed in our small cohort of older
      women with breast cancer, therefore the trial was prematurely terminated. We do
      not recommend the co-administration of gemcitabine to vinorelbine in women>or=70
      years outside the setting of controlled clinical trials.

PMID- 17028244
TI  - Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed
      by esophagectomy for locally advanced esophageal cancer.
AB  - BACKGROUND: To test the feasibility of incorporating a twice-weekly paclitaxel
      (Taxol) and cisplatin regimen into concurrent chemoradiotherapy (CCRT), followed
      by surgery, for patients with locally advanced esophageal cancer. PATIENTS AND
      METHODS: Patients with operable T3N0-1M0 or T1-3N1M0 esophageal cancer were
      enrolled. The CCRT regimen included paclitaxel (35 mg/m2 1 h on days 1 and
      4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), and radiotherapy (2 Gy on
      days 1-5/week). When the accumulated radiation dose reached 40 Gy, the
      feasibility of esophagectomy was evaluated in all patients. In patients for whom
      esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. RESULTS:
      The majority of 97 patients enrolled had squamous cell carcinoma on histology
      (95%) and T3N1 disease by endoscopic ultrasonographic staging (90%). All patients
      received CCRT to 40 Gy. Sixty-one patients underwent surgery, and 26 patients
      continued definitive CCRT to 60 Gy. The intention-to-treat pathological complete
      response rate was 25% [24/97, 95% confidence interval (CI) 16-33]. At a median
      follow-up of 25.3 months, the median progression-free and overall survival was
      15.6 and 28.8 months, respectively. The most common grade 3/4 toxic effects were
      leukopenia (30%), thrombocytopenia (10%), and diarrhea (15%). CONCLUSIONS: CCRT
      with a twice-weekly paclitaxel and cisplatin regimen followed by esophagectomy is
      an active treatment of locally advanced esophageal cancer.

PMID- 17028245
TI  - The extracellular cAMP-adenosine pathway significantly contributes to the in vivo
      production of adenosine.
AB  - The extracellular cAMP-adenosine pathway is the cellular egress of cAMP followed
      by extracellular conversion of cAMP to adenosine by the sequential actions of
      ecto-phosphodiesterase and ecto-5'-nucleotidase. Although detailed studies in
      isolated organs, tissues, and cells provide evidence for an extracellular cAMP
      adenosine pathway, whether this mechanism contributes significantly to adenosine
      production in vivo is unclear. 1,3-Dipropyl-8-p-sulfophenylxanthine is restricted
      to the extracellular compartment due to a negative charge at physiological pH
      and, at high concentrations (> or =0.1 mM), blocks ecto-phosphodiesterase. Here,
      we show that administration of 1,3-dipropyl-8-p-sulfophenylxanthine at a dose
      that provided concentrations in plasma and urine of approximately 0.3 and 6 mM,
      respectively, inhibited urinary adenosine excretion. In Sprague-Dawley rats i.v.,
      1,3-dipropyl-8-p-sulfophenylxanthine (10 mg + 0.15 mg/min) significantly
      decreased by 48 and 39% the urinary excretion of adenosine (from 3.57 +/- 0.38 to
      1.87 +/- 0.14 nmol/30 min; p = 0.0003) and the ratio of urinary adenosine to cAMP
      (from 0.93 +/- 0.08 to 0.57 +/- 0.06; p = 0.0044), respectively, without altering
      blood pressure, renal blood flow, or glomerular filtration rate. Although 1,3
      dipropyl-8-p-sulfophenylxanthine transiently increased urine volume and sodium
      excretion, these effects subsided, yet adenosine excretion remained reduced.
      Thus, changes in systemic and renal hemodynamics and excretory function could not
      account for the effects of 1,3-dipropyl-8-p-sulfophenylxanthine on adenosine
      excretion. Additional experiments showed that 1,3-dipropyl-8-p
      sulfophenylxanthine, as in Sprague-Dawley rats, significantly attenuated
      adenosine excretion and the ratio of urinary adenosine to cAMP in both Wistar
      Kyoto rats and spontaneously hypertensive rats. We conclude that the
      extracellular cAMP-adenosine pathway significantly contributes to the in vivo
      production of adenosine.

PMID- 17028246
TI  - The FLIP-side of Fas signaling.

PMID- 17028247
TI  - A phase I study of in vitro expanded natural killer T cells in patients with
      advanced and recurrent non-small cell lung cancer.
AB  - PURPOSE: Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an
      invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand
      alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The
      human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been
      shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting
      a potent killing activity against various tumor cell lines. We did a phase I
      study with autologous activated Valpha24 NKT cell therapy. EXPERIMENTAL DESIGN:
      Patients with advanced or recurrent non-small cell lung cancer received i.v.
      injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5
      x 10(7)/m2) to test the safety, feasibility, and clinical response of this
      therapeutic strategy. Immunomonitoring was also done in all cases. RESULTS: Six
      patients were enrolled in this study. No severe adverse events were observed
      during this study in any patients. After the first and second injection of
      activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24
      NKT cells was observed in two of three cases receiving a level 2 dose of
      activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in
      peripheral blood mononuclear cells increased after the administration of
      activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No
      patient was found to meet the criteria for either a partial or a complete
      response. CONCLUSIONS: The clinical trial with activated Valpha24 NKT cell
      administration was well tolerated and carried out safely with minor adverse
      events even in patients with advanced diseases.

PMID- 17028248
TI  - PrP genotype progression in flocks participating in the National Scrapie Plan for
      Great Britain.
AB  - The National Scrapie Plan (NSP) for Great Britain is a voluntary scheme that,
      through PrP genotype testing and restricted breeding, aims to reduce the risk of
      scrapie in the national sheep flock. To gauge the progress in member flocks and
      within breeds, the genotype profile of successive crops of ram lambs was
      monitored between 2002 and 2004. In each of the 11 most frequently sampled
      breeds, the proportion of ram lambs testing in the most resistant genotype
      category (NSP type 1: ARR/ARR) increased, and there was a reduction in the
      proportion of genotypes associated with the highest disease risk, that is X/VRQ,
      where X is an allele other than ARR. Changes in the proportion of ram lambs
      testing for ARR-heterozygous genotypes (NSP type 2: ARR/X, where X is not VRQ)
      appeared to be influenced by whether the sheep were hill breeds or non-hill
      breeds. In each of six frequently sampled hill breeds these genotypes expanded,
      in relative terms, whereas they declined in four of five prominent
      lowland/crossing breeds. The proportion of ram lambs that carried neither ARR nor
      VRQ (NSP type 3) declined consistently in the top 11 breeds, but there was little
      change in the ARR/VRQ genotype (NSP type 4). Among individual flocks that had ram
      lambs tested in all three years 2002 to 2004, the majority experienced an
      increase in the proportion testing ARR/ARR, and of those that had VRQ ram lambs
      in 2002, most recorded a decrease in their frequency by 2004.

PMID- 17028249
TI  - Effects of two diets on the haematology, plasma chemistry and intestinal flora of
      budgerigars (Melopsittacus undulatus).
AB  - Two groups of 22 budgerigars (Melopsittacus undulatus) were housed for 12 months
      under identical conditions. One group was fed a commercial seed mixture plus
      carrots and a mineral supplement, and the other group was fed a commercially
      formulated diet plus carrots. Samples of blood and faeces were collected
      initially and after three, six, nine and 12 months. There were no significant
      differences between the haematological values of the two groups. The group fed
      the seed mixture had significantly higher concentrations of glucose, albumin,
      triglycerides and uric acid, and higher activity of aspartate aminotransferase,
      but the values were within the published reference ranges for normal birds. There
      were no significant differences between the faecal samples from the two groups,
      except that the fungus Macrorhabdus ornithogaster was identified in 48.3 per cent
      of the samples from the group fed the commercially formulated diet but from only
      3.4 per cent of the samples from the group fed the seed mixture.

PMID- 17028250
TI  - Metallic foreign bodies in the tongues of 16 horses.
AB  - The history, clinical signs, results of diagnostic imaging, treatment methods and
      outcome of 16 adult horses with a metallic foreign body in the tongue are
      reviewed. All the horses had a swollen tongue, they salivated excessively and
      were partially to completely anorexic. Less common clinical signs were fever, an
      enlarged and painful intermandibular space, dysphagia, unilateral tongue
      paralysis and halitosis. Most of the horses had shown clinical signs for less
      than 24 hours. The foreign bodies were diagnosed by oral examination, radiography
      and ultrasonography; they were removed from the tongue of four of the horses
      during the initial oral examination, and were removed surgically from nine
      others; the other three horses were treated medically without attempts being made
      to extract the foreign bodies. Twelve of the bodies were small pieces of wire and
      one was a hypodermic needle. All the horses received a combination of
      antimicrobial and non-steroidal anti-inflammatory drugs and they all made an
      uneventful recovery. Feeding hay and the use of cable-framed tractor tyres as
      feeders were commonly associated with the cases.

PMID- 17028251
TI  - Low-dose dexamethasone test with "inverse" results: a possible new pattern of
      cortisol response.

PMID- 17028252
TI  - Treatment of penile prolapse in horses using a modified Buhner suture technique.

PMID- 17028253
TI  - Lower urinary tract obstruction in a Mediterranean spur-thighed tortoise (Testudo
      graeca) with coxofemoral arthritis.

PMID- 17028254
TI  - Primary orthostatic tremor in a Scottish deerhound.

PMID- 17028255
TI  - Deaths in aviary birds associated with protozoal megaloschizonts.

PMID- 17028257
TI  - Practitioners' views.

PMID- 17028258
TI  - Treatment of ovine caseous lymphadenitis.

PMID- 17028259
TI  - Pathophysiological correlates of two unique renal tubule lesions in rats with
      intestinal resection.
AB  - Rats with small bowel resection fed a high-oxalate diet develop extensive
      deposition of calcium oxalate (CaOx) and calcium phosphate crystals in the kidney
      after 4 mo. To explore the earliest sites of renal crystal deposition, rats
      received either small bowel resection or transection and were then fed either
      standard chow or a high-oxalate diet; perfusion-fixed renal tissue from five rats
      in each group was examined by light microscopy at 2, 4, 8, and 12 wk. Rats fed
      the high-oxalate diet developed birefringent microcrystals at the brush border of
      proximal tubule cells, with or without cell damage; the lesion was most common in
      rats with both resection and a high-oxalate diet (10/19 with the lesion) and was
      significantly correlated with urine oxalate excretion (P < 0.001). Rats with
      bowel resection fed normal chow had mild hyperoxaluria but high urine CaOx
      supersaturation; four of these rats developed birefringent crystal deposition
      with tubule plugging in inner medullary collecting ducts (IMCD). Two rats fed a
      high-oxalate diet also developed this lesion, which was correlated with CaOx
      supersaturation, but not oxalate excretion. Tissue was examined under oil
      immersion, and tiny birefringent crystals were noted on the apical surface of
      IMCD cells only in animals with IMCD crystal plugging. In one animal, IMCD
      crystals were both birefringent and nonbirefringent, suggesting a mix of CaOx and
      calcium phosphate. Overall, these animals demonstrate two distinct sites and
      mechanisms of renal crystal deposition and may help elucidate renal lesions seen
      in humans with enteric hyperoxaluria and stones.

PMID- 17028260
TI  - Expression and functional characteristics of tubular transporters: P
      glycoprotein, PEPT1, and PEPT2 in renal mass reduction and diabetes.
AB  - Renal mass reduction is associated with a compromise in renal excretion, and thus
      dosages of drugs need to be adjusted to avoid adverse reactions and to ensure
      their effectiveness. A prototypic example is patients who had undergone
      transplantation due to a variety of causes, including diabetic nephropathy; the
      latter appears to be the major cause of renal failure requiring hemodialysis and
      transplantation. Conceivably, hyperglycemia with reduced renal mass interferes in
      the delivery of xenobiotics handled by various tubular transporters. In this
      investigation, effect of renal mass reduction/hyperglycemia on gene and protein
      expression of P-glycoprotein (Pgp), PEPT1, and PEPT2 was assessed. Also,
      [H(3)]glycylsarcosine uptake, a prototype of dipeptide, was measured in various
      groups of rats: sham-operated, uninephrectomized, streptozotocin-induced
      diabetes, and diabetic + uninephrectomized. An increase in Pgp, PEPT1, and PEPT2
      expression was observed in kidneys of uninephrectomy rats, the highest being in
      the Pgp. Similarly, an increase was observed in diabetic rats who had undergone
      uninephrectomy, although less than those with nephrectomy alone. No differences
      were observed between sham-operated and diabetic groups. Increased uptake of
      [H(3)]glycylsarcosine was also seen in uninephrectomised rats. A modest uptake
      was observed in diabetic rats who had undergone uninephrectomy. The data suggest
      that uninephrectomy induces an increase in the expression and activity of
      transporters localized to renal tubular epithelial brush border. The fact that
      upregulation and activity of the peptide transporters were less in kidneys of
      diabetic animals who had undergone uninephrectomy compared with uninephrectomy
      alone suggests that hyperglycemia interferes in their expression and activity
      during the compensatory phase.

PMID- 17028261
TI  - Epithelial repair is inhibited by an alpha(1,6)-fucose binding lectin.
AB  - The effective repair of damage to the airway epithelium is essential to maintain
      the ability to exclude airborne particulates and protect against potential
      pathogens. Carbohydrates on the cell surface have an important role in cell-cell
      and cell substrate interactions. Using a model of repair with airway epithelial
      derived cells of the 16HBE 14o(-) cell line, we have examined the effect of the
      Aleuria aurantia lectin (AAL), which binds very selectively to alpha(1,6)-linked
      fucose residues. Addition of unconjugated or FITC-labeled AAL reduced the rate of
      epithelial repair to approximately one-third of control values as measured by
      image analysis while cell viability was maintained. Pulse labeling with AAL-FITC
      for 30 min followed by incubation in AAL-free medium caused similar inhibition of
      repair but could be reversed by addition of fucose up to 7 h after AAL removal.
      By confocal microscopy, AAL binding was found to be on the apical, but not
      basolateral, surfaces of cells, and internalization of the labeled lectin was
      seen. Preincubation of the lectin with fucose prevented this effect. Ulex
      europeaus I lectin, which is also fucose specific, resulted in similar binding to
      the cells and internalization, but it did not affect the speed of the repair
      process. We conclude that alpha(1,6)-fucose binding sites play an important role
      in epithelial repair. Better understanding of this process will provide a deeper
      insight into the crucial mechanisms of epithelial repair.

PMID- 17028262
TI  - Prostaglandin E(2) inhibits collagen expression and proliferation in patient
      derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling.
AB  - Uncontrolled fibroblast activation is one of the hallmarks of fibrotic lung
      disease. Prostaglandin E(2) (PGE(2)) has been shown to inhibit fibroblast
      migration, proliferation, collagen deposition, and myofibroblast differentiation
      in the lung. Understanding the mechanisms for these effects may provide insight
      into the pathogenesis of fibrotic lung disease. Previous work has focused on
      commercially available fibroblast cell lines derived from tissue whose precise
      origin and histopathology are often unknown. Here, we sought to define the
      mechanism of PGE(2) inhibition in patient-derived fibroblasts from peripheral
      lung verified to be histologically normal. Fibroblasts were grown from explants
      of resected lung, and proliferation and collagen I expression was determined
      following treatment with PGE(2) or modulators of its receptors and downstream
      signaling components. PGE(2) inhibited fibroblast proliferation by 33% and
      collagen I expression by 62%. PGE(2) resulted in a 15-fold increase in
      intracellular cAMP; other cAMP-elevating agents inhibited collagen I in a manner
      similar to PGE(2). These effects were reproduced by butaprost, a PGE(2) analog
      selective for the cAMP-coupled E prostanoid (EP) 2 receptor, but not by selective
      EP3 or EP4 agonists. Fibroblasts expressed both major cAMP effectors, protein
      kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1), but only a
      selective PKA agonist was able to appreciably inhibit collagen I expression.
      Treatment with okadaic acid, a phosphatase inhibitor, potentiated the effects of
      PGE(2). Our data indicate that PGE(2) inhibits fibroblast activation in primary
      lung fibroblasts via binding of EP2 receptor and production of cAMP; inhibition
      of collagen I proceeds via activation of PKA.

PMID- 17028263
TI  - Diesel exhaust particulate-induced activation of Stat3 requires activities of
      EGFR and Src in airway epithelial cells.
AB  - In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory
      responses in the lung characterized by inflammatory cell influx and elevated
      expression of mediators such as cytokines and chemokines. Signal transducers and
      activators of transcription (STAT) proteins are a family of cytoplasmic
      transcription factors that are key transducers of signaling in response to
      cytokine and growth factor stimulation. One member of the STAT family, Stat3, has
      been implicated as a regulator of inflammation but has not been studied in regard
      to DEP exposure. The results of this study show that DEP induces Stat3
      phosphorylation as early as 1 h following stimulation and that phosphorylated
      Stat3 translocates into the nucleus. Inhibition of epidermal growth factor
      receptor (EGFR) and Src activities by the inhibitors PD-153035 and PP2,
      respectively, abolished the activation of Stat3 by DEP, suggesting that Stat3
      activation by DEP requires EGFR and Src kinase activation. The present study
      suggests that oxidative stress induced by DEP may play a critical role in
      activating EGFR signaling, as evidenced by the fact that pretreatment with
      antioxidant prevented the activation of EGFR and Stat3. These findings
      demonstrate that DEP inhalation can activate proinflammatory Stat3 signaling in
      vitro.

PMID- 17028264
TI  - Cell-based tissue engineering for lung regeneration.
AB  - Emphysema is a chronic lung disease characterized by alveolar enlargement and
      tissue loss. Tissue engineering represents an attractive potential for
      regeneration of several organ systems. The complex three-dimensional
      architectural structure of lung parenchyma requiring connections of alveolar
      units to airways and the pulmonary circulation makes this strategy less
      optimistic. In the present study, we used Gelfoam sponge as a scaffold material,
      supplemented with fetal rat lung cells as progenitors, to explore the potential
      application of cell-based tissue engineering for lung regeneration in adult rats.
      After injection into lung parenchyma, the sponge showed porous structures similar
      to alveolar units. It did not induce severe local inflammatory response. Fetal
      lung cells in the sponge were able to survive in the adult lung for at least 35
      days, determined by CMTMR [5-(and-6)-{[(4
      chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells
      within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling.
      Cells formed "alveolar-like structures" at the border between the sponge and the
      surrounding lung tissue with positive immunohistochemical staining for epithelial
      and endothelial cells. Neovascularization of the sponge was demonstrated with
      India ink perfusion. The sponge degraded after several months. This study
      suggests that cell-based tissue engineering possesses the potential to regenerate
      alveolar-like structures, an important step towards our ultimate goal of lung
      regeneration.

PMID- 17028265
TI  - Regulation of urokinase receptor expression by protein tyrosine phosphatases.
AB  - Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a major
      role in several physiological processes such as cell migration, proliferation,
      morphogenesis, and regulation of gene expression. Many of the biological
      activities of uPA depend on its association with uPAR. uPAR expression and its
      induction by uPA are regulated at the posttranscriptional level. Inhibition of
      protein tyrosine phosphatase-mediated dephosphorylation by sodium orthovanadate
      induces uPAR expression and, with uPA, additively induces cell surface uPAR
      expression. Sodium orthovanadate induces uPAR by increasing uPAR mRNA in a time-
      and concentration-dependent manner. Both sodium orthovanadate and uPA induce uPAR
      mRNA stability, indicating that dephosphorylation could contribute to uPA-induced
      posttranscriptional regulation of uPAR expression. Induction of the tyrosine
      phosphatase SHP2 in Beas2B and H157 cells inhibits basal cell surface uPAR
      expression and uPA-induced uPAR expression. Sodium orthovanadate also increases
      uPAR expression by decreasing the interaction of a uPAR mRNA coding region
      sequence with phosphoglycerate kinase (PGK) as well as by enhancing the
      interaction between a uPAR mRNA 3' untranslated sequence with heterogeneous
      nuclear ribonucleoprotein C (hnRNPC). On the contrary, overexpression of SHP2 in
      Beas2B cells increased interaction of PGK with the uPAR mRNA coding region and
      inhibited hnRNPC binding to the 3' untranslated sequence. These findings confirm
      a novel mechanism by which uPAR expression of lung airway epithelial cells is
      regulated at the level of mRNA stability by inhibition of protein tyrosine
      phosphatase-mediated dephosphorylation of uPAR mRNA binding proteins and
      demonstrate that the process involves SHP2.

PMID- 17028266
TI  - Increased lung expansion alters lung growth but not alveolar epithelial cell
      differentiation in newborn lambs.
AB  - Although increased lung expansion markedly alters lung growth and epithelial cell
      differentiation during fetal life, the effect of increasing lung expansion after
      birth is unknown. We hypothesized that increased basal lung expansion, caused by
      ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would
      stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and
      decrease surfactant protein mRNA levels. Two groups of lambs were sedated and
      ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n =
      5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group
      of nonventilated 2-wk-old lambs was used for comparison. We determined wet and
      dry lung weights, DNA and protein content, a labeling index for proliferating
      cells, surfactant protein mRNA expression, and proportions of AECs using electron
      microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not
      affect total lung DNA or protein, it significantly increased the proportion of
      proliferating cells in the lung when compared with nonventilated 2-wk-old
      controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP:
      1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed
      in AEC proportions or surfactant protein mRNA levels between either of the
      ventilated groups. This study demonstrates that increases in end-expiratory lung
      volumes, induced by the application of PEEP, lead to increased lung growth in
      mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.

PMID- 17028267
TI  - Cyclic stretch induces PlGF expression in bronchial airway epithelial cells via
      nitric oxide release.
AB  - Mechanical strain of lung tissue is an important stimulus for the production of
      growth factors that are critical for lung growth and development. However,
      excessive mechanical strain, as may occur during mechanical ventilation, may
      produce an increase in growth factors that may contribute to lung injury. We
      hypothesized that mechanical strain of primary bronchial airway epithelial cells
      (BAEpCs) induced the production of placental growth factor (PlGF), a member of
      the VEGF family. BAEpCs were cultured on a deformable silicoelastic membrane and
      exposed to different magnitudes of stretch. Stretch induced PlGF and nitric oxide
      (NO) production that increased with increasing magnitude of stretch. Stretch also
      induced PlGF and inducible NO synthase (iNOS) gene expression. The stretch
      induced PlGF production and NO synthesis were attenuated by PD98059, a specific
      mitogen-activated protein kinase kinase-1 and -2 inhibitor. Inhibition of NO
      generation by l-NAME or l-NMMA or scavenging NO by carboxy-PTIO prevented stretch
      mediated erk1/2 activation. In addition, in unstretched BAEpCs, exogenous NO
      enhanced erk1/erk2 activation. Our data suggest that mechanical stretch of BAEpCs
      induces iNOS expression and induces PlGF release in an erk1/2 activation
      dependent manner.

PMID- 17028268
TI  - Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and
      in transgenic mice.
AB  - The notch gene family encodes transmembrane receptors that regulate cell
      differentiation by interacting with surface ligands on adjacent cells.
      Previously, we demonstrated that tumor necrosis factor-alpha (TNF) induces
      neuroendocrine (NE) cell differentiation in H82, but not H526, undifferentiated
      small cell lung carcinoma lines. We now test the hypothesis that TNF mediates NE
      cell differentiation in part by altering Notch gene expression. First, using RT
      PCR, we determined that TNF treatment of H82, but not H526, transiently decreases
      notch-1 mRNA in parallel with induction of gene expression for the NE-specific
      marker DOPA decarboxylase (DDC). Second, we treated H82 and H526 with notch-1
      antisense vs. sense oligodeoxynucleotides. Using quantitative RT-PCR and Western
      analyses we demonstrate that DDC mRNA and protein are increased in H82 by notch-1
      antisense, whereas notch-1 mRNA and activated Notch-1 protein are decreased. mRNA
      for Hes1, a transcription factor downstream from activated Notch, is also
      decreased by Notch-1 antisense in H82 but not H526. After 7 days of Notch-1
      antisense treatment, neural cell adhesion molecule (NCAM) immunoreactivity is
      induced in H82 but not H526. Third, we generated transgenic mice bearing notch-1
      driven by the neural/NE-specific calcitonin promoter, which express activated
      Notch-1 in developing lung epithelium. Newborn NotchCal mouse lungs have high
      levels of hes1 mRNA, reflecting increased activated Notch, compared with wild
      type. NotchCal lungs have decreased CGRP-positive NE cells, decreased protein
      gene product 9.5 (PGP9.5)-positive NE cells, and decreased gastrin-releasing
      peptide (GRP), CGRP, and DDC mRNA levels compared with normal littermates.
      Cumulatively, these observations provide further support for a role for Notch-1
      signaling in regulating pulmonary NE cell differentiation.

PMID- 17028269
TI  - Population genetics and linkage analysis of loci within the FCT region of
      Streptococcus pyogenes.
AB  - The FCT regions of Streptococcus pyogenes strains encode a variety of cell wall
      anchored surface proteins that bind the extracellular matrix of the human host
      and/or give rise to pilus-like appendages. Strong linkage is evident between
      transcription-regulatory loci positioned within the FCT and emm regions and the
      emm pattern genotype marker for preferred infection of the throat or skin. These
      findings provide a basis for the hypothesis that FCT region gene products
      contribute to tissue-specific infection. In an initial series of steps to address
      this possibility, the FCT regions of 13 strains underwent comparative sequence
      analysis, the gene content of the FCT region was characterized for 113 strains
      via PCR, and genetic linkage was assessed. A history of extensive recombination
      within FCT regions was evident. The emm pattern D-defined skin specialist strains
      were highly homogenous in their FCT region gene contents, whereas the emm pattern
      A-C-defined throat specialist strains displayed a greater variety of forms. Most
      pattern A-C strains harbored prtF1 (75%) but lacked cpa (75%). In contrast, the
      majority of emm pattern D strains had cpa (92%) but lacked prtF1 (79%). Models
      based on FCT and emm region genotypes revealed the most parsimonious pathways of
      evolution. Using niche-determining candidate genes to infer phylogeny, emm
      pattern E strains--the so-called generalists, which lack a strong tissue site
      preference--occupied a transition zone separating most throat specialists from
      skin specialists. Overall, population genetic analysis supports the possibility
      that the FCT region gives rise to surface proteins that are largely necessary,
      but not always sufficient, to confer tissue site preference for infection.

PMID- 17028270
TI  - Time-resolved determination of the CcpA regulon of Lactococcus lactis subsp.
      cremoris MG1363.
AB  - Carbon catabolite control protein A (CcpA) is the main regulator involved in
      carbon catabolite repression in gram-positive bacteria. Time series gene
      expression analyses of Lactococcus lactis MG1363 and L. lactis MG1363DeltaccpA
      using DNA microarrays were used to define the CcpA regulon of L. lactis. Based on
      a comparison of the transcriptome data with putative CcpA binding motifs (cre
      sites) in promoter sequences in the genome of L. lactis, 82 direct targets of
      CcpA were predicted. The main differences in time-dependent expression of CcpA
      regulated genes were differences between the exponential and transition growth
      phases. Large effects were observed for carbon and nitrogen metabolic genes in
      the exponential growth phase. Effects on nucleotide metabolism genes were
      observed primarily in the transition phase. Analysis of the positions of putative
      cre sites revealed that there is a link between either repression or activation
      and the location of the cre site within the promoter region. Activation was
      observed when putative cre sites were located upstream of the hexameric -35
      sequence at an average position of -56.5 or further upstream with decrements of
      10.5 bp. Repression was observed when the cre site was located in or downstream
      of putative -35 and -10 sequences. The highest level of repression was observed
      when the cre site was present at a defined side of the DNA helix relative to the
      canonical -10 sequence. Gel retardation experiments, Northern blotting, and
      enzyme assays showed that CcpA represses its own expression and activates the
      expression of the divergently oriented prolidase-encoding pepQ gene, which
      constitutes a link between regulation of carbon metabolism and regulation of
      nitrogen metabolism.

PMID- 17028271
TI  - The two-component regulatory system TCS08 is involved in cellobiose metabolism of
      Streptococcus pneumoniae R6.
AB  - The two-component system TCS08 is one of the regulatory systems that is important
      for virulence of Streptococcus pneumoniae. In order to investigate the TCS08
      regulon, we have analyzed transcription profiles of mutants derived from S.
      pneumoniae R6 by microarray analysis. Since deletion mutants are often without a
      significant phenotype, we constructed a mutation in the histidine kinase HK08,
      T133P, in analogy to the phosphatase mutation T230P in the H box of the S.
      pneumoniae CiaH kinase described recently (D. Zahner, K. Kaminski, M. van der
      Linden, T. Mascher, M. Merai, and R. Hakenbeck, J. Mol. Microbiol. Biotechnol.
      4:211-216, 2002). In addition, a deletion mutation was constructed in rr08,
      encoding the cognate response regulator. The most heavily suppressed genes in the
      hk08 mutant were spr0276 to spr0282, encoding a putative cellobiose
      phosphoenolpyruvate sugar phosphotransferase system (PTS). Whereas the R6 Sm(r)
      parent strain and the Deltarr08 mutant readily grew on cellobiose, the hk08
      mutant and selected mutants with deletions in the PTS cluster did not, strongly
      suggesting that TCS08 is involved in the catabolism of cellobiose. Homologues of
      the TCS08 system were found in closely related streptococci and other gram
      positive cocci. However, the genes spr0276 to spr0282, encoding the putative
      cellobiose PTS, represent a genomic island in S. pneumoniae and homologues were
      found in Streptococcus gordonii only, suggesting that this system might
      contribute to the pathogenicity potential of the pneumococcus.

PMID- 17028272
TI  - The gene cluster for agmatine catabolism of Enterococcus faecalis: study of
      recombinant putrescine transcarbamylase and agmatine deiminase and a snapshot of
      agmatine deiminase catalyzing its reaction.
AB  - Enterococcus faecalis makes ATP from agmatine in three steps catalyzed by
      agmatine deiminase (AgDI), putrescine transcarbamylase (PTC), and carbamate
      kinase (CK). An antiporter exchanges putrescine for agmatine. We have cloned the
      E. faecalis ef0732 and ef0734 genes of the reported gene cluster for agmatine
      catabolism, overexpressed them in Escherichia coli, purified the products,
      characterized them functionally as PTC and AgDI, and crystallized and X-ray
      diffracted them. The 1.65-Angstroms-resolution structure of AgDI forming a
      covalent adduct with an agmatine-derived amidine reactional intermediate is
      described. We provide definitive identification of the gene cluster for agmatine
      catabolism and confirm that ornithine is a genuine but poor PTC substrate,
      suggesting that PTC (found here to be trimeric) evolved from ornithine
      transcarbamylase. N-(Phosphonoacetyl)-putrescine was prepared and shown to
      strongly (K(i) = 10 nM) and selectively inhibit PTC and to improve PTC
      crystallization. We find that E. faecalis AgDI, which is committed to ATP
      generation, closely resembles the AgDIs involved in making polyamines, suggesting
      the recruitment of a polyamine-synthesizing AgDI into the AgDI pathway. The
      arginine deiminase (ADI) pathway of arginine catabolism probably supplied the
      genes for PTC and CK but not those for the agmatine/putrescine antiporter, and
      thus the AgDI and ADI pathways are not related by a single "en bloc" duplication
      event. The AgDI crystal structure reveals a tetramer with a five-blade propeller
      subunit fold, proves that AgDI closely resembles ADI despite a lack of sequence
      identity, and explains substrate affinity, selectivity, and Cys357-mediated
      covalent catalysis. A three-tongued agmatine-triggered gating opens or blocks
      access to the active center.

PMID- 17028273
TI  - Lysophosphatidylethanolamine is a substrate for the short-chain alcohol
      dehydrogenase SocA from Myxococcus xanthus.
AB  - Short-chain alcohol dehydrogenases (SCADHs) synthesize a variety of intercellular
      signals and other chemically diverse products. It is difficult to predict the
      substrate of a SCADH on the basis of amino acid sequence homology, as the
      substrates are not known for most SCADHs. In Myxococcus xanthus, the SCADH CsgA
      is responsible for C signaling during fruiting body development, although the
      mechanism is unclear. Overexpression of the SCADH SocA compensates for the lack
      of CsgA and restores development and C signaling in csgA mutants. The potential
      of SocA in generating the C signal enzymatically was explored by developing a
      dehydrogenase assay-based screen to purify the SocA substrate(s). A SocA
      substrate was extracted from M. xanthus cells with acidified ethyl acetate and
      sequentially purified by solid-phase extraction on silica gel and by reverse
      phase high-performance liquid chromatography. The fraction with the highest SocA
      dehydrogenase activity contained the lysophospholipid 1-acyl 2-hydroxy-sn
      glycerophosphoethanolamine (lyso-PE) as indicated by the fragment ions and a
      phosphatidylethanolamine-specific neutral loss scan following liquid
      chromatography coupled to mass spectrometry. The abundant lysophospholipid with
      the mass m/z 450 (molecular ion [M-H]-) had a monounsaturated acyl chain with 16
      carbons. SocA oxidizes lyso-PE containing either saturated or unsaturated fatty
      acids but exhibits poor activity on l-alpha-glycerophosphorylethanolamine,
      suggesting that an acyl chain is important for activity. Of the five different
      head groups, only ethanolamine showed appreciable activity. The apparent Km and
      Vmax for lyso-PE 18:1 were 116 microM and 875 micromol min(-1) mg(-1),
      respectively. The catalytic efficiency (k(cat)/Km) was 1 x 10(8) M(-1) s(-1). The
      proposed product, 1-acyloxy-3-(2-aminoethylphosphatyl) acetone was unstable, and
      the fragmented products were unable to rescue csgA mutant development. The active
      fraction from thin-layer chromatography also contained an unidentified SocA
      substrate that had morphogenic properties.

PMID- 17028274
TI  - Characterization of XynC from Bacillus subtilis subsp. subtilis strain 168 and
      analysis of its role in depolymerization of glucuronoxylan.
AB  - Secretion of xylanase activities by Bacillus subtilis 168 supports the
      development of this well-defined genetic system for conversion of
      methylglucuronoxylan (MeGAXn [where n represents the number of xylose residues])
      in the hemicellulose component of lignocellulosics to biobased products. In
      addition to the characterized glycosyl hydrolase family 11 (GH 11) endoxylanase
      designated XynA, B. subtilis 168 secretes a second endoxylanase as the translated
      product of the ynfF gene. This sequence shows remarkable homology to the GH 5
      endoxylanase secreted by strains of Erwinia chrysanthemi. To determine its
      properties and potential role in the depolymerization of MeGAXn, the ynfF gene
      was cloned and overexpressed to provide an endoxylanase, designated XynC, which
      was characterized with respect to substrate preference, kinetic properties, and
      product formation. With different sources of MeGAXn as the substrate, the
      specific activity increased with increasing methylglucuronosyl substitutions on
      the beta-1,4-xylan chain. With MeGAXn from sweetgum as a preferred substrate,
      XynC exhibited a Vmax of 59.9 units/mg XynC, a Km of 1.63 mg MeGAXn/ml, and a
      k(cat) of 2,635/minute at pH 6.0 and 37 degrees C. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometry and 1H nuclear magnetic
      resonance data revealed that each hydrolysis product has a single glucuronosyl
      substitution penultimate to the reducing terminal xylose. This detailed analysis
      of XynC from B. subtilis 168 defines the unique depolymerization process
      catalyzed by the GH 5 endoxylanases. Based upon product analysis, B. subtilis 168
      secretes both XynA and XynC. Expression of xynA was subject to MeGAXn induction;
      xynC expression was constitutive with growth on different substrates. Translation
      and secretion of both GH 11 and GH 5 endoxylanases by the fully sequenced and
      genetically malleable B. subtilis 168 recommends this bacterium for the
      introduction of genes required for the complete utilization of products of the
      enzyme-catalyzed depolymerization of MeGAXn. B. subtilis may serve as a model
      platform for development of gram-positive biocatalysts for conversion of
      lignocellulosic materials to renewable fuels and chemicals.

PMID- 17028275
TI  - Heme biosynthesis in Methanosarcina barkeri via a pathway involving two
      methylation reactions.
AB  - The methanogenic archaeon Methanosarcina barkeri synthesizes protoheme via
      precorrin-2, which is formed from uroporphyrinogen III in two consecutive
      methylation reactions utilizing S-adenosyl-L-methionine. The existence of this
      pathway, previously exclusively found in the sulfate-reducing delta
      proteobacterium Desulfovibrio vulgaris, was demonstrated for M. barkeri via the
      incorporation of two methyl groups from methionine into protoheme.

PMID- 17028276
TI  - nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of
      Pseudomonas aeruginosa.
AB  - The Pseudomonas aeruginosa nalD gene encodes a TetR family repressor with
      homology to the SmeT and TtgR repressors of the smeDEF and ttgABC multidrug
      efflux systems of Stenotrophomonas maltophilia and Pseudomonas putida,
      respectively. A sequence upstream of mexAB-oprM and overlapping a second promoter
      for this efflux system was very similar to the SmeT and TtgR operator sequences,
      and NalD binding to this region was, in fact, demonstrated. Moreover, increased
      expression from this promoter was seen in a nalD mutant, consistent with NalD
      directly controlling mexAB-oprM expression from a second promoter.

PMID- 17028277
TI  - RhlR expression in Pseudomonas aeruginosa is modulated by the Pseudomonas
      quinolone signal via PhoB-dependent and -independent pathways.
AB  - The expression of virulence determinants in Pseudomonas aeruginosa is
      coordinately regulated in response to both the social environment--commonly
      referred to as quorum sensing--and to environmental cues. In this study we have
      dissected the various independent regulation levels for pyocyanin production,
      which is influenced by the homoserine lactone- and Pseudomonas quinolone signal
      (PQS)-mediated quorum-sensing systems as well as by iron and phosphate
      availability. We demonstrate that the phosphate regulon is involved in the
      transcriptional activation of rhlR and the augmentation of PQS and pyocyanin
      production under phosphate limitation. However, we also observed an enhancement
      of rhlR transcription under low-iron medium conditions and after the addition of
      PQS that was independent of the phosphate regulon. These results highlight the
      complexity of secondary metabolite production in P. aeruginosa via environmental
      cues and the quorum-sensing system.

PMID- 17028278
TI  - Overlapping and specialized functions of the molybdenum-dependent regulators MopA
      and MopB in Rhodobacter capsulatus.
AB  - The phototrophic purple bacterium Rhodobacter capsulatus encodes two similar but
      functionally not identical molybdenum-dependent regulator proteins (MopA and
      MopB), which are known to replace each other in repression of the modABC genes
      (coding for an ABC-type high-affinity Mo transport system) and anfA (coding for
      the transcriptional activator of Fe-nitrogenase genes). We identified further Mo
      regulated (mor) genes coding for a putative ABC-type transport system of unknown
      function (MorABC) and a putative Mo-binding protein (Mop). The genes coding for
      MopA and the ModABC transporter form part of a single transcriptional unit, mopA
      modABCD, as shown by reverse transcriptase PCR. Immediately upstream of mopA and
      transcribed in the opposite direction is mopB. The genes coding for the putative
      MorABC transporter belong to two divergently transcribed operons, morAB and morC.
      Expression studies based on lacZ reporter gene fusions in mutant strains
      defective for either MopA, MopB, or both revealed that the regulators substitute
      for each other in Mo-dependent repression of morAB and morC. Specific Mo
      dependent activation of the mop gene by MopA, but not MopB, was found to control
      the putative Mo-binding protein. Both MopA and MopB are thought to bind to
      conserved DNA sequences with dyad symmetry in the promoter regions of all target
      genes. The positions of these so-called Mo boxes relative to the transcription
      start sites (as determined by primer extension analyses) differed between Mo
      repressed genes and the Mo-activated mop gene. DNA mobility shift assays showed
      that MopA and MopB require molybdenum to bind to their target sites with high
      affinity.

PMID- 17028279
TI  - Mesorhizobium loti produces nodPQ-dependent sulfated cell surface
      polysaccharides.
AB  - Leguminous plants and bacteria from the family Rhizobiaceae form a symbiotic
      relationship, which culminates in novel plant structures called root nodules. The
      indeterminate symbiosis that forms between Sinorhizobium meliloti and alfalfa
      requires biosynthesis of Nod factor, a beta-1,4-linked lipochitooligosaccharide
      that contains an essential 6-O-sulfate modification. S. meliloti also produces
      sulfated cell surface polysaccharides, such as lipopolysaccharide (LPS). The
      physiological function of sulfated cell surface polysaccharides is unclear,
      although mutants of S. meliloti with reduced LPS sulfation exhibit symbiotic
      abnormalities. Using a bioinformatic approach, we identified a homolog of the S.
      meliloti carbohydrate sulfotransferase, LpsS, in Mesorhizobium loti. M. loti
      participates in a determinate symbiosis with the legume Lotus japonicus. We
      showed that M. loti produces sulfated forms of LPS and capsular polysaccharide
      (KPS). To investigate the physiological function of sulfated polysaccharides in
      M. loti, we identified and disabled an M. loti homolog of the sulfate-activating
      genes, nodPQ, which resulted in undetectable amounts of sulfated cell surface
      polysaccharides and a cysteine auxotrophy. We concomitantly disabled an M. loti
      cysH homolog, which disrupted cysteine biosynthesis without reducing cell surface
      polysaccharide sulfation. Our experiments demonstrated that the nodPQ mutant, but
      not the cysH mutant, showed an altered KPS structure and a diminished ability to
      elicit nodules on its host legume, Lotus japonicus. Interestingly, the nodPQ
      mutant also exhibited a more rapid growth rate and appeared to outcompete wild
      type M. loti for nodule colonization. These results suggest that sulfated cell
      surface polysaccharides are required for optimum nodule formation but limit
      growth rate and nodule colonization in M. loti.

PMID- 17028280
TI  - A homologue of the 3-oxoacyl-(acyl carrier protein) synthase III gene located in
      the glycosylation island of Pseudomonas syringae pv. tabaci regulates virulence
      factors via N-acyl homoserine lactone and fatty acid synthesis.
AB  - Pseudomonas syringae pv. tabaci 6605 possesses a genetic region involved in
      flagellin glycosylation. This region is composed of three open reading frames:
      orf1, orf2, and orf3. Our previous study revealed that orf1 and orf2 encode
      glycosyltransferases; on the other hand, orf3 has no role in posttranslational
      modification of flagellin. Although the function of Orf3 remained unclear, an
      orf3 deletion mutant (Deltaorf3 mutant) had reduced virulence on tobacco plants.
      Orf3 shows significant homology to a 3-oxoacyl-(acyl carrier protein) synthase
      III in the fatty acid elongation cycle. The Deltaorf3 mutant had a significantly
      reduced ability to form acyl homoserine lactones (AHLs), which are quorum-sensing
      molecules, suggesting that Orf3 is required for AHL synthesis. In comparison with
      the wild-type strain, swarming motility, biosurfactant production, and tolerance
      to H2O2 and antibiotics were enhanced in the Deltaorf3 mutant. A scanning
      electron micrograph of inoculated bacteria on the tobacco leaf surface revealed
      that there is little extracellular polymeric substance matrix surrounding the
      cells in the Deltaorf3 mutant. The phenotypes of the Deltaorf3 mutant and an AHL
      synthesis (DeltapsyI) mutant were similar, although the mutant-specific
      characteristics were more extreme in the Deltaorf3 mutant. The swarming motility
      of the Deltaorf3 mutant was greater than that of the DeltapsyI mutant. This was
      attributed to the synergistic effects of the overproduction of biosurfactants
      and/or alternative fatty acid metabolism in the Deltaorf3 mutant. Furthermore,
      the amounts of iron and biosurfactant seem to be involved in biofilm development
      under quorum-sensing regulation in P. syringae pv. tabaci 6605.

PMID- 17028281
TI  - Rapid evolution of diminished transformability in Acinetobacter baylyi.
AB  - The reason for genetic exchange remains a crucial question in evolutionary
      biology. Acinetobacter baylyi strain ADP1 is a highly competent and
      recombinogenic bacterium. We compared the parallel evolution of wild-type and
      engineered noncompetent lineages of A. baylyi in the laboratory. If
      transformability were to result in an evolutionary benefit, it was expected that
      competent lineages would adapt more rapidly than noncompetent lineages. Instead,
      regardless of competency, lineages adapted to the same extent under several
      laboratory conditions. Furthermore, competent lineages repeatedly evolved a much
      lower level of transformability. The loss of competency may be due to a selective
      advantage or the irreversible transfer of loss-of-function alleles of genes
      required for transformation within the competent population.

PMID- 17028282
TI  - Cyclic di-GMP signaling in bacteria: recent advances and new puzzles.

PMID- 17028283
TI  - Mycoplasma genitalium P140 and P110 cytadhesins are reciprocally stabilized and
      required for cell adhesion and terminal-organelle development.
AB  - Mycoplasma genitalium is a human pathogen that mediates cell adhesion by a
      complex structure known as the attachment organelle. This structure is composed
      of cytadhesins and cytadherence-associated proteins, but few data are available
      about the specific role of these proteins in M. genitalium cytadherence. We have
      deleted by homologous recombination the mg191 and mg192 genes from the MgPa
      operon encoding the P140 and P110 cytadhesins. Molecular characterization of
      these mutants has revealed a reciprocal posttranslational stabilization between
      the two proteins. Loss of either P140 or P110 yields a hemadsorption-negative
      phenotype and correlates with decreased or increased levels of cytoskeleton
      related proteins MG386 and DnaK, respectively. Scanning electron microscopy
      analysis reveals the absolute requirement of P140 and P110 for the proper
      development of the attachment organelle. The phenotype described for these
      mutants resembles that of the spontaneous class I and class II cytadherence
      negative mutants [G. R. Mernaugh, S. F. Dallo, S. C. Holt, and J. B. Baseman,
      Clin. Infect. Dis. 17(Suppl. 1):S69-S78, 1993], whose genetic basis remained
      undetermined until now. Complementation assays and sequencing analysis
      demonstrate that class I and class II mutants are the consequence of large
      deletions affecting the mg192 and mg191-mg192 genes, respectively. These
      deletions originated from single-recombination events involving sequences of the
      MgPa operon and the MgPa island located immediately downstream. We also
      demonstrate the translocation of MgPa sequences to a particular MgPa island by
      double-crossover events. Based on these observations, we propose that in addition
      to being a source of antigenic variation, MgPa islands could be also involved in
      a general phase variation mechanism switching on and off, in a reversible or
      irreversible way, the adhesion properties of M. genitalium.

PMID- 17028284
TI  - Mycobacterium tuberculosis SigM positively regulates Esx secreted protein and
      nonribosomal peptide synthetase genes and down regulates virulence-associated
      surface lipid synthesis.
AB  - The Mycobacterium tuberculosis genome encodes 12 alternative sigma factors,
      several of which regulate stress responses and are required for virulence in
      animal models of acute infection. In this work we investigated M. tuberculosis
      SigM, a member of the extracytoplasmic function subfamily of alternative sigma
      factors. This sigma factor is expressed at low levels in vitro and does not
      appear to function in stress response regulation. Instead, SigM positively
      regulates genes required for the synthesis of surface or secreted molecules.
      Among these are genes encoding two pairs of Esx secreted proteins, a multisubunit
      nonribosomal peptide synthetase operon, and genes encoding two members of the
      proline-proline-glutamate (PPE) family of proteins. Genes up regulated in a sigM
      mutant strain include a different PPE gene, as well as several genes involved in
      surface lipid synthesis. Among these are genes involved in synthesis of
      phthiocerol dimycocerosate (PDIM), a surface lipid critical for virulence during
      acute infection, and the kasA-kasB operon, which is required for mycolic acid
      synthesis. Analysis of surface lipids showed that PDIM synthesis is increased in
      a sigM-disrupted strain and is undetectable in a sigM overexpression strain.
      These findings demonstrate that SigM positively and negatively regulates cell
      surface and secreted molecules that are likely to function in host-pathogen
      interactions.

PMID- 17028285
TI  - Biosynthetic pathways of inositol and glycerol phosphodiesters used by the
      hyperthermophile Archaeoglobus fulgidus in stress adaptation.
AB  - Archaeoglobus fulgidus accumulates di-myo-inositol phosphate (DIP) and diglycerol
      phosphate (DGP) in response to heat and osmotic stresses, respectively, and the
      level of glycero-phospho-myo-inositol (GPI) increases primarily when the two
      stresses are combined. In this work, the pathways for the biosynthesis of these
      three compatible solutes were established based on the detection of the relevant
      enzymatic activities and characterization of the intermediate metabolites by
      nuclear magnetic resonance analysis. The synthesis of DIP proceeds from glucose-6
      phosphate via four steps: (i) glucose-6-phosphate was converted into l-myo
      inositol 1-phosphate by l-myo-inositol 1-phosphate synthase; (ii) l-myo-inositol
      1-phosphate was activated to CDP-inositol at the expense of CTP; this is the
      first demonstration of CDP-inositol synthesis in a biological system; (iii) CDP
      inositol was coupled with l-myo-inositol 1-phosphate to yield a phosphorylated
      intermediate, 1,1'-di-myo-inosityl phosphate 3-phosphate (DIPP); (iv) finally,
      DIPP was dephosphorylated into DIP by the action of a phosphatase. The synthesis
      of the two other polyol-phosphodiesters, DGP and GPI, proceeds via the
      condensation of CDP-glycerol with the respective phosphorylated polyol, glycerol
      3-phosphate for DGP and l-myo-inositol 1-phosphate for GPI, yielding the
      respective phosphorylated intermediates, 1X,1'X-diglyceryl phosphate 3-phosphate
      (DGPP) and 1-(1X-glyceryl) myo-inosityl phosphate 3-phosphate (GPIP), which are
      subsequently dephosphorylated to form the final products. The results disclosed
      here represent an important step toward the elucidation of the regulatory
      mechanisms underlying the differential accumulation of these compounds in
      response to heat and osmotic stresses.

PMID- 17028286
TI  - The parsing of food reward.

PMID- 17028287
TI  - Vagal afferents are essential for maximal resection-induced intestinal adaptive
      growth in orally fed rats.
AB  - Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine
      process thought to involve both sympathetic and parasympathetic innervation and
      enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated
      whether capsaicin-sensitive vagal afferent neurons are essential for maximal
      resection-induced intestinal growth. Rats received systemic or perivagal
      capsaicin or ganglionectomy before 70% midjejunoileal resection or transection
      and were fed orally or by total parenteral nutrition (TPN) for 7 days after
      surgery. Growth of residual bowel was assessed by changes in mucosal mass,
      protein, DNA, and histology. Both systemic and perivagal capsaicin significantly
      attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein,
      and DNA in rats fed orally. Villus height was significantly reduced in resected
      rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal
      mucosa was not significantly different; ileal mucosal sucrase specific activity
      was significantly increased by resection in capsaicin-treated rats. Capsaicin did
      not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in
      plasma concentration of bioactive GLP-2 resulting from resection in orally fed
      rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to
      attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not
      attenuate resection-induced mucosal growth. We conclude that vagal afferents are
      not essential for GLP-2 secretion when the ileum has direct contact with luminal
      nutrients after resection. In summary, vagal afferent neurons are essential for
      maximal resection-induced intestinal adaptation through a mechanism that appears
      to involve stimulation by luminal nutrients.

PMID- 17028288
TI  - Editorial: The SERM of my dreams.

PMID- 17028289
TI  - Editorial: Mortality and renal disease in type 1 diabetes mellitus--progress
      made, more to be done.

PMID- 17028290
TI  - Editorial: Anti-Mullerian hormone: Cinderella finds new admirers.

PMID- 17028291
TI  - Editorial: Metabolism lessons for survival: when adults and children are not
      alike.

PMID- 17028292
TI  - Understanding the presence and function of erythropoietin receptors on cancer
      cells.

PMID- 17028293
TI  - Do erythropoietin receptors on cancer cells explain unexpected clinical findings?
AB  - PURPOSE: Recent reports suggest that cancer control may worsen if erythropoietin
      is administered. We investigated whether erythropoietin receptor expression on
      cancer cells may correlate with this unexpected finding. PATIENTS AND METHODS:
      Cancer tissue from patients with advanced carcinoma of the head and neck (T3, T4,
      or nodal involvement) and scheduled for radiotherapy was assayed retrospectively
      for erythropoietin receptor expression by immunohistochemistry. Patients were
      anemic and randomized to receive epoetin beta (300 U/kg) or placebo under double
      blind conditions, given three times weekly starting 10 to 14 days before and
      continuing throughout radiotherapy. We administered 60 Gy following complete
      resection or 64 Gy subsequent to microscopically incomplete resection; 70 Gy were
      given following macroscopically incomplete resection or for definitive
      radiotherapy alone. We determined if the effect of epoetin beta on locoregional
      progression-free survival was correlated with the expression of erythropoietin
      receptors on cancer cells using a Cox proportional hazards regression model.
      RESULTS: We studied 154 of 157 randomly assigned patients; 104 samples were
      positive, and 50 were negative for receptor expression. Locoregional progression
      free survival was substantially poorer if epoetin beta was administered to
      patients positive for receptor expression compared with placebo (adjusted
      relative risk, 2.07; 95% CI, 1.27 to 3.36; P < .01). In contrast, epoetin beta
      did not impair outcome in receptor-negative patients (adjusted relative risk,
      0.94; 95% CI, 0.47 to 1.90; P = .86). The difference in treatment associated
      relative risks (2.07 v 0.94) was borderline statistically significant (P = .08).
      CONCLUSION: Erythropoietin might adversely affect prognosis of head and neck
      cancer patients if cancer cells express erythropoietin receptors.

PMID- 17028294
TI  - Molecular and pathologic aspects of endometrial carcinogenesis.
AB  - Endometrial cancer is the most common gynecological malignancy, with 41,000 new
      cases projected in the United States for 2006. Two different clinicopathologic
      subtypes are recognized: the estrogen-related (type I, endometrioid) and the non
      estrogen-related types (type II, nonendometrioid such as papillary serous and
      clear cell). The morphologic differences in these cancers are mirrored in their
      molecular genetic profile with type I showing defects in DNA-mismatch repair and
      mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy and
      p53 mutations. This article reviews the genetic aspects of endometrial
      carcinogenesis and progression. We will define the precursor lesion of type I
      endometrioid cancer and the role of genetics and estrogen in its progression.

PMID- 17028295
TI  - Elaborate petals in Australian Spermacoce (Rubiaceae) species: morphology,
      ontogeny and function.
AB  - BACKGROUND AND AIMS: Australian Spermacoce species display various types of
      elaborate petals. Their precise morphology, ontogenetic origin, and function are
      hitherto unknown. The aim of the present paper is to unravel the development and
      nature of the diverse types of elaborate petals in Spermacoce through a floral
      ontogenetic study. METHODS: The floral ontogeny of six species characterized by
      different types of corolla appendages was studied by scanning electron microscopy
      and light microscopy. In order to elucidate the possible functions of the
      elaborate petals, field observations were conducted as well. KEY RESULTS:
      Scanning electronmicrographs show that full-grown petals of Spermacoce lignosa,
      S. phaeosperma and S. redacta bear appendages on their ventral side. Despite
      their different appearance at anthesis, the appendages develop very similarly in
      all three species. They are initiated at the same developmental stage and are
      first visible as two arcs of primordia converging from the upper margins of the
      petal towards its midvein and downwards. In S. brevidens, S. caudata and S.
      erectiloba, the full-grown petals have two long, concave protuberances, which
      develop from the tissue at both sides of the petal's mid-vein. In these three
      species, initiation of appendages on the ventral side of the petals is also
      observed, but they are hardly visible on the mature petals. The two types of
      elaborate petals tightly enclose the anthers, both in bud and during most of the
      flowering period. CONCLUSIONS: Among Australian Spermacoce species, two types of
      elaborate petals can be distinguished. The former hypothesis that the two types
      of elaborate petals are essentially homologous is here rejected. Field
      investigations point out that the elaborate petals might play a role in the
      pollination biology of the species.

PMID- 17028297
TI  - alpha-Pinene inhibits growth and induces oxidative stress in roots.
AB  - BACKGROUND AND AIMS: Determining the mode of action of allelochemicals is one of
      the challenging aspects in allelopathic studies. Recently, allelochemicals have
      been proposed to cause oxidative stress in target tissue and induce an
      antioxidant mechanism. alpha-Pinene, one of the common monoterpenoids emitted
      from several aromatic plants including forest trees, is known for its growth
      inhibitory activity. However, its mechanism of action remains unexplored. The aim
      of the present study was to determine the inhibitory effect of alpha-pinene on
      root growth and generation of reactive oxygen species, as indicators of oxidative
      stress and changes in activities of antioxidant enzymes. METHODS: Effects of
      alpha-pinene on early root growth were studied in five test species, Cassia
      occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer
      arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation,
      proline accumulation, and activities of the enzymes superoxide dismutase (SOD),
      ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and
      glutathione reductase (GR) were studied in roots of C. occidentalis. KEY RESULTS:
      alpha-Pinene inhibited the radicle growth of all the test species. Exposure of C.
      occidentalis roots to alpha-pinene enhanced solute leakage, and increased levels
      of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation
      and induction of oxidative stress. Activities of the antioxidant enzymes SOD,
      CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced
      generation of reactive oxygen species (ROS) upon alpha-pinene exposure. Increased
      levels of scavenging enzymes indicates their induction as a secondary defence
      mechanism in response to alpha-pinene. CONCLUSIONS: It is concluded that alpha
      pinene inhibits early root growth and causes oxidative damage in root tissue
      through enhanced generation of ROS, as indicated by increased lipid peroxidation,
      disruption of membrane integrity and elevated antioxidant enzyme levels.

PMID- 17028296
TI  - Drought, abscisic acid and transpiration rate effects on the regulation of PIP
      aquaporin gene expression and abundance in Phaseolus vulgaris plants.
AB  - BACKGROUND AND AIMS: Drought causes a decline of root hydraulic conductance,
      which aside from embolisms, is governed ultimately by aquaporins. Multiple
      factors probably regulate aquaporin expression, abundance and activity in leaf
      and root tissues during drought; among these are the leaf transpiration rate,
      leaf water status, abscisic acid (ABA) and soil water content. Here a study is
      made of how these factors could influence the response of aquaporin to drought.
      METHODS: Three plasma membrane intrinsic proteins (PIPs) or aquaporins were
      cloned from Phaseolus vulgaris plants and their expression was analysed after 4 d
      of water deprivation and also 1 d after re-watering. The effects of ABA and of
      methotrexate (MTX), an inhibitor of stomatal opening, on gene expression and
      protein abundance were also analysed. Protein abundance was examined using
      antibodies against PIP1 and PIP2 aquaporins. At the same time, root hydraulic
      conductance (L), transpiration rate, leaf water status and ABA tissue
      concentration were measured. KEY RESULTS: None of the treatments (drought, ABA or
      MTX) changed the leaf water status or tissue ABA concentration. The three
      treatments caused a decline in the transpiration rate and raised PVPIP2;1 gene
      expression and PIP1 protein abundance in the leaves. In the roots, only the
      drought treatment raised the expression of the three PIP genes examined, while at
      the same time diminishing PIP2 protein abundance and L. On the other hand, ABA
      raised both root PIP1 protein abundance and L. CONCLUSIONS: The rise of PvPIP2;1
      gene expression and PIP1 protein abundance in the leaves of P. vulgaris plants
      subjected to drought was correlated with a decline in the transpiration rate. At
      the same time, the increase in the expression of the three PIP genes examined
      caused by drought and the decline of PIP2 protein abundance in the root tissues
      were not correlated with any of the parameters measured.

PMID- 17028298
TI  - Seasonal timing of pseudoviviparous reproduction of Leiothrix (Eriocaulaceae)
      rupestrian species in South-eastern Brazil.
AB  - BACKGROUND AND AIMS: Pseudovivipary is an asexual reproductive strategy.
      Leiothrix spiralis and L. vivipara (Eriocaulaceae) are pseudoviviparous and occur
      in rupestrian grasslands, a habitat that has a predominance of sandy and shallow
      soil, with low water retention. This study aims to investigate the seasonal
      variation effect of moisture availability on L. spiralis and L. vivipara
      pseudoviviparous reproduction, and to compare their life history attributes, on
      rupestrian grasslands in Southeastern Brazil. METHODS: A field study was
      conducted, including observations concerning pseudoviviparous reproduction and
      measurement of demographic variables in both L. spiralis and L. vivipara. Soil
      moisture measurements were also performed to study its effect on the
      pseudoviviparous reproduction of L. spiralis and L. vivipara. KEY RESULTS: Flower
      head and plantlet production in L. spiralis were highly correlated with soil
      moisture. All scapes split off in the drier period, indicating that this is a
      splitter ramet species. Plantlet mortality was positively correlated with scapes
      splitting off. The L. vivipara phenophases were not synchronized to the variation
      in soil moisture, since flower heads and plantlets were produced throughout the
      year. Moreover, the splitting off of scapes was not observed. In addition,
      plantlets were formed early, as soon as the flower heads appeared, and remained
      suspended. Therefore, this species was called 'canopy forming'. CONCLUSIONS:
      Seasonal timing of pseudoviviparous reproduction can be a vital component of the
      successful establishment of plantlets in L. spiralis, considering that in this
      species the plantlets are formed only after the flower head touches the ground.
      In contrast, in L. vivipara, the plantlets are formed early, without touching the
      ground. Moreover, L. spiralis is a splitter ramet species, while L. vivipara is a
      canopy-forming species. The pseudoviviparous canopy-forming strategy appears to
      be more advantageous than the splitter ramet strategy, because even under similar
      soil moisture conditions, the survival of L. vivipara plantlets was greater than
      that of L. spiralis.

PMID- 17028299
TI  - Summer dormancy in perennial temperate grasses.
AB  - BACKGROUND AND AIMS: Dormancy has been extensively studied in plants which
      experience severe winter conditions but much less so in perennial herbaceous
      plants that must survive summer drought. This paper reviews the current knowledge
      on summer dormancy in both native and cultivated perennial temperate grasses
      originating from the Mediterranean Basin, and presents a unified terminology to
      describe this trait. SCOPE: Under severe drought, it is difficult to separate the
      responses by which plants avoid and tolerate dehydration from those associated
      with the expression of summer dormancy. Consequently, this type of endogenous
      (endo-) dormancy can be tested only in plants that are not subjected to moisture
      deficit. Summer dormancy can be defined by four criteria, one of which is
      considered optional: (1) reduction or cessation of leaf production and expansion;
      (2) senescence of mature foliage; (3) dehydration of surviving organs; and (4,
      optional) formation of resting organs. The proposed terminology recognizes two
      levels of summer dormancy: (a) complete dormancy, when cessation of growth is
      associated with full senescence of foliage and induced dehydration of leaf bases;
      and (b) incomplete dormancy, when leaf growth is partially inhibited and is
      associated with moderate levels of foliage senescence. Summer dormancy is
      expressed under increasing photoperiod and temperature. It is under hormonal
      control and usually associated with flowering and a reduction in metabolic
      activity in meristematic tissues. Dehydration tolerance and dormancy are
      independent phenomena and differ from the adaptations of resurrection plants.
      CONCLUSIONS: Summer dormancy has been correlated with superior survival after
      severe and repeated summer drought in a large range of perennial grasses. In the
      face of increasing aridity, this trait could be used in the development of
      cultivars that are able to meet agronomic and environmental goals. It is
      therefore important to have a better understanding of the genetic and
      environmental control of summer dormancy.

PMID- 17028300
TI  - Proteomic identification of macrophage migration-inhibitory factor upon exposure
      to TiO2 particles.
AB  - Inhalation of particulate matter aggravates respiratory symptoms in patients with
      chronic airway diseases, but the mechanisms underlying this response remain
      poorly understood. We used a proteomics approach to examine this phenomenon.
      Treatment of epithelial cells with BSA-coated titanium dioxide (TiO(2)) particles
      altered 20 protein spots on the two-dimensional gel, and these were then analyzed
      by nano-LC-MS/MS. These proteins included defense-related, cell-activating, and
      cytoskeletal proteins implicated in the response to oxidative stress. The
      proteins were classified into four groups according to the time course of their
      expression patterns. For validation, RT-PCR was performed on extracts of in vitro
      TiO(2)-treated cells, and lung issues from TiO(2)-treated rats were analyzed by
      immunohistochemical staining and enzyme immunoassay. TiO(2) treatment was found
      to increase the amount of mRNA for macrophage migration-inhibitory factor (MIF).
      MIF was expressed primarily in epithelium and was elevated in lung tissues and
      bronchoalveolar lavage fluids of TiO(2)-treated rats as compared with sham
      treated rats. Carbon black and diesel exhaust particles also induced expression
      of MIF protein in the epithelial cells.

PMID- 17028301
TI  - Morphine administration alters the profile of hippocampal postsynaptic density
      associated proteins: a proteomics study focusing on endocytic proteins.
AB  - Numerous studies have shown that drugs of abuse induce changes in protein
      expression in the brain that are thought to play a role in synaptic plasticity.
      Drug-induced plasticity can be mediated by changes at the synapse and more
      specifically at the postsynaptic density (PSD), which receives and transduces
      synaptic information. To date, the majority of studies examining synaptic protein
      profiles have focused on identifying the synaptic proteome. Only a handful of
      studies have examined the changes in synaptic profile by drug administration. We
      applied a quantitative proteomics analysis technique with the cleavable ICAT
      reagent to quantitate relative changes in protein levels of the hippocampal PSD
      in response to morphine administration. We identified a total of 102 proteins in
      the mouse hippocampal PSD. The majority of these were signaling, trafficking, and
      cytoskeletal proteins involved in synaptic plasticity, learning, and memory.
      Among the proteins whose levels were found to be altered by morphine
      administration, clathrin levels were increased to the largest extent.
      Immunoblotting and electron microscopy studies showed that this increase was
      localized to the PSD. Morphine treatment was also found to lead to a local
      increase in two other components of the endocytic machinery, dynamin and AP-2,
      suggesting a critical involvement of the endocytic machinery in the modulatory
      effects of morphine. Because alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptors are thought to undergo clathrin-mediated endocytosis, we
      examined the effect of morphine administration on the association of the AMPA
      receptor subunit, GluR1, with clathrin. We found a substantial decrease in the
      levels of GluR1 associated with clathrin. Taken together, these results suggest
      that, by causing a redistribution of endocytic proteins at the synapse, morphine
      modulates synaptic plasticity at hippocampal glutamatergic synapses.

PMID- 17028302
TI  - MicroRNAs in biological processes and carcinogenesis.
AB  - MicroRNAs (miRNAs) encoding small non-coding RNAs have been recognized as a very
      large gene family present in most organisms. The precise biological effects of
      miRNAs are yet to be elucidated in detail, partly because each miRNA is believed
      to negatively regulate the expression of hundreds of target genes. Nevertheless,
      recent findings indicate that carcinogenic processes are associated with
      alterations in the expression of several miRNAs, suggesting that some function as
      oncogenes or tumor suppressor genes. The present review focuses on recent
      findings in this exciting new area of research, with special emphasis on the
      involvement of miRNAs in cancer development and progression. Further studies are
      clearly warranted to elucidate the molecular and biological roles of miRNAs,
      which may ultimately provide both a better understanding of disease development,
      as well as a foundation for novel strategies for cancer diagnosis and therapy.

PMID- 17028303
TI  - Association of DNA repair polymorphisms with DNA repair functional outcomes in
      healthy human subjects.
AB  - We investigated association between polymorphisms in DNA repair genes and the
      capacity to repair DNA damage induced by gamma-irradiation and by base oxidation
      in a healthy population. Irradiation-specific DNA repair rates were significantly
      decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45
      +/- 0.47 SSB/10(9) Da) than in those with wild-type genotype (1.10 +/- 0.70
      SSB/10(9) Da, P=0.0006, Mann-Witney U-test). The capacity to repair oxidative DNA
      damage was significantly decreased among individuals with hOGG1 Ser326Cys
      homozygous variant genotype (0.37 +/- 0.28 SSB/10(9) Da) compared to those with
      wild-type genotype (0.83 +/- 0.79 SSB/10(9) Da, P=0.008, Mann-Witney U-test).
      Investigation of genotype combinations showed that the increasing number of
      variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms
      resulted in a significant decrease of irradiation-specific repair rates (P=0.008,
      Kruskal-Wallis test). Irradiation-specific DNA repair rates also decreased with
      increasing number of variant alleles in XRCC1 Arg399Gln in combination with
      variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His
      (P=0.002 and P=0.005, respectively; Kruskal-Wallis test). In a binary combination
      variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were
      associated with a significant decrease in the capacity to repair DNA oxidative
      damage (P=0.018, Kruskal-Wallis test). In summary, XRCC1 Arg399Gln and hOGG1
      Ser326Cys polymorphisms seem to exert the predominant modulating effect on
      irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative
      damage, respectively.

PMID- 17028304
TI  - Examining treatment use among alcohol-dependent individuals from a population
      perspective.
AB  - AIMS: To assess the prevalence of treatment use in lifetime and past year alcohol
      dependent respondents. To establish the proportion of problem drinkers who use
      alcohol treatment that just go to one treatment versus attending multiple
      different types of treatment in the same year. To explore what treatments are
      most likely to form part of a multiple treatment package. METHOD: Analysis of the
      2001-2002 National Epidemiologic Survey of Alcohol and Related Conditions, a
      large (N = 43 039), representative survey of the non-institutionalized adult
      population of the USA. There were 4781 respondents who met criteria for a
      lifetime definition of alcohol dependence and 1484 respondents who met criteria
      for past year alcohol dependence. RESULTS: Prevalence of lifetime use of alcohol
      treatment was 25% among those with a lifetime diagnosis of alcohol dependence.
      Prevalence of past year use of alcohol treatment was 12% among respondents with
      past year alcohol dependence. Only one-third of past year treatment users had
      accessed just one type of alcohol treatment. CONCLUSIONS: While treatment
      services are only used by the minority of people with alcohol dependence, those
      people who do access alcohol treatment are likely to use several different
      alcohol treatment services in the same year.

PMID- 17028305
TI  - Drinking histories of self-identified lifetime abstainers and occasional
      drinkers: findings from the 1958 British Birth Cohort Study.
AB  - AIMS: To investigate the validity of retrospective items used to distinguish
      people who have rarely or never consumed alcohol. METHODS: The 1958 British Birth
      Cohort Study has followed 9377 individuals until age 45. Previous drinking (at
      16, 23, 33 and 42 years) was investigated for two groups of 45-year-old non
      drinkers, those reporting never having consumed alcohol ('never drinkers', n =
      143, 1.5%), and having only consumed very infrequently ('occasional-only
      drinkers', n = 1149, 12.3%). RESULTS: 67% of never drinkers previously reported
      drinking, 25% were past weekly/daily drinkers; 56% of occasional-only drinkers
      reported weekly/daily consumption. The validity of the retrospective items was
      progressively questionable when presumed to cover longer time periods.
      CONCLUSIONS: Substantial measurement error was evident when identifying
      'occasional-only' and 'never' drinkers using retrospective items covering the
      lifecourse. Researchers investigating potential health benefits associated with
      moderate drinking need to incorporate more sophisticated methods when identifying
      sub-groups of non-drinkers.

PMID- 17028306
TI  - Lipid peroxidation and serum cytokines in acute alcoholic hepatitis.
AB  - AIMS: Increased exposure of Kupffer cells to intestinal-borne Gram-negative
      bacteria enhances the metabolism and leads to cytokine production by these cells.
      Activation of Kupffer cells increases free radical release, which may, in turn,
      enhance cytokine secretion, creating a positive feedback loop, which contributes
      to liver inflammation. Cytokines act on T cells, inducing their proliferation and
      secretion of additional interleukins. Lipid peroxidation products
      (malondialdehyde; MDA) form adducts with proteins and acetaldehyde, triggering a
      T cell immune response. Controversy exists about the predominance of either Th-1
      or Th-2 cellular responses. We performed the present study in order to analyse
      the cytokine pattern in patients with acute alcoholic hepatitis, its relation to
      MDA and the relation between all these parameters and liver function and
      prognosis. SUBJECTS AND METHODS: The study included 53 male alcoholics, 47
      followed up for a median time of 32 months, during which 17 of them died. We
      measured serum MDA, tumour necrosis factor-alpha, interferon gamma (IFNG) and
      interleukins (IL) 4, 6, 8, and 10. RESULTS: MDA levels were raised in cirrhotics
      and non-cirrhotics with alcoholic hepatitis, maintaining a relationship with
      bilirubin and Maddrey index, and with mortality in the univariate analysis. Both
      IFNG and IL-4 were raised in our patients compared with controls, as well as IL
      8, and IL-6, but IL-10 were below the detection limit in the majority of cases,
      especially in cirrhotics. Using a Cox regression model, Maddrey index displaced
      MDA in the survival analysis. CONCLUSIONS: Our data lend support to the
      hypothesis that activation of both Th-1 and Th-2 cell subsets take place. MDA
      levels are raised in alcoholics with alcoholic hepatitis and are closely related
      to liver function derangement and to survival, although this is displaced by
      Maddrey index using Cox regression model.

PMID- 17028307
TI  - The life and times of the J-shaped curve.

PMID- 17028308
TI  - Assessing motivation for change in subjects with alcohol problems: the MAC2-A
      questionnaire.
AB  - AIMS: This article presents the validation study of a questionnaire (MAC2-A),
      created to assess motivation for change in Italian adult subjects with alcohol
      related problems who require or are referred for assessment and treatment. The
      questionnaire evaluates readiness to change (RTC), self-efficacy and discrepancy.
      METHODS: The questionnaire was validated on 419 subjects referred to 23 health
      agencies in Italy. RESULTS: The questionnaire showed good internal consistency
      and temporal stability. Exploratory and confirmatory factor analysis confirms the
      consistency with the theoretical assumptions. Test-retest showed high reliability
      on all scales except one. Visual analogue control scales used for reliability and
      concurrent validity yielded strong correlations with the corresponding variables.
      CONCLUSION: The study confirms the validity of the instrument, and its
      consistency with the model. The MAC2-A questionnaire is the first psychometric
      instrument integrating three factors (discrepancy, self-efficacy, RTC) into a 3D
      model of motivation for change.

PMID- 17028309
TI  - Differential enzymatic characteristics and tissue-specific expression of human
      TPST-1 and TPST-2.
AB  - Protein tyrosine sulfation is emerging as a widespread post-translational
      modification in multicellular eukaryotes. The responsible enzyme, named
      tyrosylprotein sulfotransferase (TPST), catalyzes the sulfate transfer from 3'
      phosphoadenosine 5'-phosphosulfate to tyrosine residues of proteins. Two distinct
      TPSTs, designated TPST-1 and TPST-2, had previously been identified. In the
      present study, we cloned human TPST-1 and TPST-2 expressed and characterized the
      recombinant enzymes using peptide substrates. These enzymes displayed distinct
      acidic pH optima and stimulatory effects of Mn(2+). Additionally, the activity of
      TPST-2, but not TPST-1, was stimulated in the presence of Mg(2+). Compared with
      TPST-2, TPST-1 displayed considerably lower K(m) and V(max) for the majority of
      the tested peptide substrates, implying their differential substrate specificity.
      Quantitative real-time PCR analysis showed that although the two TPSTs were co
      expressed in all 20 human tissues examined, the levels of expression of TPST-1
      and TPST-2 varied significantly among different tissues. These latter findings
      may imply distinct physiological functions of TPST-1 and TPST-2.

PMID- 17028310
TI  - Language and memory disorder in the case of Jonathan Swift: considerations on
      retrospective diagnosis.
AB  - The cause of behavioural changes described by Alzheimer for his original case,
      Auguste D., has been recently reconfirmed by histological examination. However,
      there has been active speculation regarding the cause of behavioural changes
      exhibited by the political satirist Jonathan Swift (1667-1745) during the final
      three years of his life for over 250 years. Swift's symptoms of cognitive
      changes, memory impairment, personality alterations, language disorder and facial
      paralysis have all been apportioned differing levels of significance in various
      attempts at retrospective diagnosis. The various medical arguments put forward
      from the 18th through 20th centuries will be critically examined. The diagnoses
      considered refer to evolving theories of insanity, phrenology, localization of
      cortical function, hydrocephalus, psychoanalysis, aphasia, dementia and
      depression in ageing. Re-consideration of the attempts to re-diagnose Swift's
      final mental state by the leading neurological thinkers of the day, including
      Wilde (The Closing Years of Dean Swift's Life. Dublin: Hodges and Smith, 1849),
      Bucknill (1882), Osler [Osler's textbook Principles and Practice of Medicine
      (1892); published in St Thomas's Hospital Gazette (London) 1902; 12: 59-60),
      Brain (Irish Med J 1952: 320-1 and 337-346) and Boller and Forbes (J Neurol Sci
      1998; 158: 125-133) reveal the changing attitudes regarding the significance of
      behavioural symptoms to neurological diagnosis from the 18th century to the
      present day.

PMID- 17028311
TI  - Thiorphan, a neutral endopeptidase inhibitor used for diarrhoea, is
      neuroprotective in newborn mice.
AB  - Excitotoxic damage appears to be a critical factor in the formation of perinatal
      brain lesions associated with cerebral palsy (CP). When injected into newborn
      mice, the glutamatergic analogue, ibotenate, produces cortical lesions and white
      matter cysts that mimic human perinatal brain lesions. Neuropeptides are neuronal
      activity modulators and could therefore modulate glutamate-induced lesions.
      However, neuropeptides are rapidly degraded by peptidases. Racecadotril, which is
      rapidly metabolized to its active metabolite thiorphan, is a neutral
      endopeptidase (NEP) inhibitor used in clinical practice for diarrhoea with a
      remarkable safety profile. This study aimed to test the original hypothesis that
      thiorphan could be neuroprotective against ibotenate-induced lesions in newborn
      mice. Intraperitoneal administration of thiorphan reduced ibotenate-induced
      cortical lesions by up to 57% and cortical caspase-3 cleavage by up to 59%. This
      neuroprotective effect was long-lasting and was still observed when thiorphan was
      administered 12 h after the insult, showing a remarkable window for therapeutic
      intervention. Further supporting the neuroprotective effect of pharmacological
      blockade of NEP, mouse pups with a genetic deletion of NEP displayed a
      significantly reduced size of the ibotenate-induced cortical grey matter lesion
      when compared with wild-type animals. Thiorphan effects were mimicked by
      substance P (SP) and, in a less potent manner, by neurokinin A. Thiorphan effects
      were inhibited by blockers of NK1 and NK2 receptors. Real-time reverse
      transcription-polymerase chain reaction, autoradiography and immunohistochemistry
      confirmed the expression of NK1 and NK2 receptors in the neonatal murine
      neocortex. These data demonstrate that thiorphan prevents neonatal excitotoxic
      cortical damage, an effect largely mediated by SP. Thiorphan could represent a
      promising drug for the prevention of CP, which remains a challenging disease. In
      a broader context, these results also raise potential implications for the
      prevention of neurodegenerative diseases involving glutamate-mediated excitotoxic
      neuronal death.

PMID- 17028312
TI  - Correlation of mRNA expression and protein abundance affected by multiple
      sequence features related to translational efficiency in Desulfovibrio vulgaris:
      a quantitative analysis.
AB  - The modest correlation between mRNA expression and protein abundance in large
      scale data sets is explained in part by experimental challenges, such as
      technological limitations, and in part by fundamental biological factors in the
      transcription and translation processes. Among various factors affecting the mRNA
      protein correlation, the roles of biological factors related to translation are
      poorly understood. In this study, using experimental mRNA expression and protein
      abundance data collected from Desulfovibrio vulgaris by DNA microarray and liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) proteomic
      analysis, we quantitatively examined the effects of several translational
      efficiency-related sequence features on mRNA-protein correlation. Three classes
      of sequence features were investigated according to different translational
      stages: (i) initiation, Shine-Dalgarno sequences, start codon identity, and start
      codon context; (ii) elongation, codon usage and amino acid usage; and (iii)
      termination, stop codon identity and stop codon context. Surprisingly, although
      it is widely accepted that translation initiation is the rate-limiting step for
      translation, our results showed that the mRNA-protein correlation was affected
      the most by the features at elongation stages, i.e., codon usage and amino acid
      composition (5.3-15.7% and 5.8-11.9% of the total variation of mRNA-protein
      correlation, respectively), followed by stop codon context and the Shine-Dalgarno
      sequence (3.7-5.1% and 1.9-3.8%, respectively). Taken together, all sequence
      features contributed to 15.2-26.2% of the total variation of mRNA-protein
      correlation. This study provides the first comprehensive quantitative analysis of
      the mRNA-protein correlation in bacterial D. vulgaris and adds new insights into
      the relative importance of various sequence features in prokaryotic protein
      translation.

PMID- 17028313
TI  - De novo exon duplication in a new allele of mouse Glra1 (spasmodic).
AB  - The novel neurological mutant Cincinatti arose by genomic duplication of exon 5
      in the glycine receptor gene Glra1. The mutant transcript results in premature
      protein truncation. A direct repeat of the pentamer GGGGC is present adjacent to
      the breakpoints and may have mediated the duplication event by a replication
      slippage mechanism.

PMID- 17028314
TI  - An integrated in silico gene mapping strategy in inbred mice.
AB  - In recent years in silico analysis of common laboratory mice has been introduced
      and subsequently applied, in slightly different ways, as a methodology for gene
      mapping. Previously we have demonstrated some limitation of the methodology due
      to sporadic genetic correlations across the genome. Here, we revisit the three
      main aspects that affect in silico analysis. First, we report on the use of
      marker maps: we compared our existing 20,000 SNP map to the newly released
      140,000 SNP map. Second, we investigated the effect of varying strain numbers on
      power to map QTL. Third, we introduced a novel statistical approach: a cladistic
      analysis, which is well suited for mouse genetics and has increased flexibility
      over existing in silico approaches. We have found that in our examples of complex
      traits, in silico analysis by itself does fail to uniquely identify quantitative
      trait gene (QTG)-containing regions. However, when combined with additional
      information, it may significantly help to prioritize candidate genes. We
      therefore recommend using an integrated work flow that uses other genomic
      information such as linkage regions, regions of shared ancestry, and gene
      expression information to obtain a list of candidate genes from the genome.

PMID- 17028315
TI  - roX RNAs are required for increased expression of X-linked genes in Drosophila
      melanogaster males.
AB  - The male-specific lethal (MSL) ribonucleoprotein complex is necessary for
      equalization of X:A expression levels in Drosophila males, which have a single X
      chromosome. It binds selectively to the male X chromosome and directs acetylation
      of histone H4 at lysine 16 (H4Ac16), a modification linked to elevated
      transcription. roX1 and roX2 noncoding RNAs are essential but redundant
      components of this complex. Simultaneous removal of both roX RNAs reduces X
      localization of the MSL proteins and permits their ectopic binding to autosomal
      sites and the chromocenter. However, the MSL proteins still colocalize, and low
      levels of H4Ac16 are detected at ectopic sites of MSL binding and residual sites
      on the X chromosome of roX1- roX2- males. Microarray analysis was performed to
      reveal the effect of roX1 and roX2 elimination on X-linked and autosomal gene
      expression. Expression of the X chromosome is decreased by 26% in roX1- roX2-
      male larvae. Enhanced expression could not be detected at autosomal sites of MSL
      binding in roX1- roX2- males. These results implicate failure to compensate X
      linked genes, rather than inappropriate upregulation of autosomal genes at
      ectopic sites of MSL binding, as the primary cause of male lethality upon loss of
      roX RNAs.

PMID- 17028316
TI  - Cis-regulatory evolution of chalcone-synthase expression in the genus
      Arabidopsis.
AB  - The contribution of cis-regulation to adaptive evolutionary change is believed to
      be essential, yet little is known about the evolutionary rules that govern
      regulatory sequences. Here, we characterize the short-term evolutionary dynamics
      of a cis-regulatory region within and among two closely related species, A.
      lyrata and A. halleri, and compare our findings to A. thaliana. We focused on the
      cis-regulatory region of chalcone synthase (CHS), a key enzyme involved in the
      synthesis of plant secondary metabolites. We observed patterns of nucleotide
      diversity that differ among species but do not depart from neutral expectations.
      Using intra- and interspecific F1 progeny, we have evaluated functional cis
      regulatory variation in response to light and herbivory, environmental cues,
      which are known to induce CHS expression. We find that substantial cis-regulatory
      variation segregates within and among populations as well as between species,
      some of which results from interspecific genetic introgression. We further
      demonstrate that, in A. thaliana, CHS cis-regulation in response to herbivory is
      greater than in A. lyrata or A. halleri. Our work indicates that the evolutionary
      dynamics of a cis-regulatory region is characterized by pervasive functional
      variation, achieved mostly by modification of response modules to one but not all
      environmental cues. Our study did not detect the footprint of selection on this
      variation.

PMID- 17028317
TI  - Contribution of growth and cell cycle checkpoints to radiation survival in
      Drosophila.
AB  - Cell cycle checkpoints contribute to survival after exposure to ionizing
      radiation (IR) by arresting the cell cycle and permitting repair. As such, yeast
      and mammalian cells lacking checkpoints are more sensitive to killing by IR. We
      reported previously that Drosophila larvae mutant for grp (encoding a homolog of
      Chk1) survive IR as well as wild type despite being deficient in cell cycle
      checkpoints. This discrepancy could be due to differences either among species or
      between unicellular and multicellular systems. Here, we provide evidence that
      Grapes is needed for survival of Drosophila S2 cells after exposure to similar
      doses of IR, suggesting that multicellular organisms may utilize checkpoint
      independent mechanisms to survive irradiation. The dispensability of checkpoints
      in multicellular organisms could be due to replacement of damaged cells by
      regeneration through increased nutritional uptake and compensatory proliferation.
      In support of this idea, we find that inhibition of nutritional uptake (by
      starvation or onset of pupariation) or inhibition of growth factor signaling and
      downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation
      survival of larvae. Further, some of these treatments are more detrimental for
      grp mutants, suggesting that the need for compensatory proliferation is greater
      for checkpoint mutants. The difference in survival of grp and wild-type larvae
      allowed us to screen for small molecules that act as genotype-specific radiation
      sensitizers in a multicellular context. A pilot screen of a small molecule
      library from the National Cancer Institute yielded known and approved radio
      sensitizing anticancer drugs. Since radiation is a common treatment option for
      human cancers, we propose that Drosophila may be used as an in vivo screening
      tool for genotype-specific drugs that enhance the effect of radiation therapy.

PMID- 17028319
TI  - Double-strand break repair in bacteriophage T4: recombination effects of 3'-5'
      exonuclease mutations.
AB  - The role of 3'-5' exonucleases in double-strand break (DSB)-promoted
      recombination was studied in crosses of bacteriophage T4, in which DSBs were
      induced site specifically within the rIIB gene by SegC endonuclease in the DNA of
      only one of the parents. Frequency of rII+ recombinants was measured in two
      factor crosses of the type i x ets1, where ets1 designates an insertion in the
      rIIB gene carrying the cleavage site for SegC and i's are rIIB or rIIA point
      mutations located at various distances (12-2040 bp) from the ets1 site. The
      frequency/distance relationship was obtained in crosses of the wild-type phage
      and dexA1 (deficiency in deoxyribonuclease A), D219A (deficiency in the
      proofreading exonuclease of DNA polymerase), and tsL42 (antimutator allele of DNA
      polymerase) mutants. In all the mutants, recombinant frequency in crosses with
      the i-markers located at 12 and 33 bp from ets1 was significantly enhanced,
      implying better preservation of 3'-terminal sequences at the ends of the broken
      DNA. The effects of dexA1 and D219A were additive, suggesting an independent
      action of the corresponding nucleases in the DSB repair pathway. The
      recombination enhancement in the dexA1 mutant was limited to short distances
      (<100 bp from ets1), whereas in the D219A mutant a significant enhancement was
      seen at all the tested distances. From the character of the frequency/distance
      relationship, it is inferred that the synthesis-dependent strand-annealing
      pathway may operate in the D219A mutant. The recombination-enhancing effect of
      the tsL42 mutation could be explained by the hypothesis that the antimutator
      43Exo removes a shorter stretch of paired nucleotides than the wild-type enzyme
      does during hydrolysis of the unpaired terminus in the D-loop intermediate. The
      role of the proofreading exonuclease in the formation of a robust replicative
      fork is discussed.

PMID- 17028320
TI  - Diverse roles for histone H2A modifications in DNA damage response pathways in
      yeast.
AB  - There are many types of DNA damage that are repaired by a multiplicity of
      different repair pathways. All damage and repair occur in the context of
      chromatin, and histone modifications are involved in many repair processes. We
      have analyzed the roles of H2A and its modifications in repair by mutagenizing
      modifiable residues in the N- and C-terminal tails of yeast H2A and by testing
      strains containing these mutations in multiple DNA repair assays. We show that
      residues in both tails are important for homologous recombination and
      nonhomologous end-joining pathways of double-strand break repair, as well as for
      survival of UV irradiation and oxidative damage. We show that H2A serine 122 is
      important for repair and/or survival in each of these assays. We also observe a
      complex pattern of H2A phosphorylation at residues S122, T126, and S129 in
      response to different damage conditions. We find that overlapping but
      nonidentical groups of H2A residues in both tails are involved in different
      pathways of repair. These data suggest the presence of a set of H2A "damage
      codes" in which distinct patterns of modifications on both tails of H2A may be
      used to identify specific types of damage or to promote specific repair pathways.

PMID- 17028321
TI  - Roles of PriA protein and double-strand DNA break repair functions in UV-induced
      restriction alleviation in Escherichia coli.
AB  - It has been widely considered that DNA modification protects the chromosome of
      bacteria E. coli K-12 against their own restriction-modification systems.
      Chromosomal DNA is protected from degradation by methylation of target sequences.
      However, when unmethylated target sequences are generated in the host chromosome,
      the endonuclease activity of the EcoKI restriction-modification enzyme is
      inactivated by the ClpXP protease and DNA is protected. This process is known as
      restriction alleviation (RA) and it can be induced by UV irradiation (UV-induced
      RA). It has been proposed that chromosomal unmethylated target sequences, a
      signal for the cell to protect its own DNA, can be generated by homologous
      recombination during the repair of damaged DNA. In this study, we wanted to
      further investigate the genetic requirements for recombination proteins involved
      in the generation of unmethylated target sequences. For this purpose, we
      monitored the alleviation of EcoKI restriction by measuring the survival of
      unmodified lambda in UV-irradiated cells. Our genetic analysis showed that UV
      induced RA is dependent on the excision repair protein UvrA, the RecA-loading
      activity of the RecBCD enzyme, and the primosome assembly activity of the PriA
      helicase and is partially dependent on RecFOR proteins. On the basis of our
      results, we propose that unmethylated target sequences are generated at the D
      loop by the strand exchange of two hemi-methylated duplex DNAs and subsequent
      initiation of DNA replication.

PMID- 17028322
TI  - emb-4 is a conserved gene required for efficient germline-specific chromatin
      remodeling during Caenorhabditis elegans embryogenesis.
AB  - In C. elegans, germline blastomeres are initially kept transcriptionally
      quiescent by the maternally loaded CCCH zinc-finger protein PIE-1. PIE-1
      disappears upon the birth of the primordial germ cells Z2 and Z3, yet these cells
      appear to remain quiescent. We have previously demonstrated that there is a
      chromatin-based repression that succeeds PIE-1 degradation. The chromatin in
      Z2/Z3 loses certain histone modifications, including histone H3 lysine 4
      dimethylation (H3K4me2), a conserved marker for transcriptionally competent
      chromatin. We find that mutations in the maternal-effect gene emb-4 cause defects
      in both PIE-1 degradation and germline-specific chromatin remodeling. emb-4
      encodes a highly conserved protein with orthologs in fly, mouse, and human and
      has a subtle role in Notch signaling. The embryonic phenotype of emb-4 is
      consistent with a defect in the efficient and timely activation of developmental
      programs, including germline chromatin remodeling. We also find that, as in early
      somatic blastomeres, the degradation of PIE-1 in Z2/Z3 is facilitated by zinc
      finger-interacting protein ZIF-1, and in the absence of either zif-1 or emb-4,
      PIE-1 is abnormally retained in Z2/Z3.

PMID- 17028318
TI  - Evolution of amino-acid sequences and codon usage on the Drosophila miranda neo
      sex chromosomes.
AB  - We have studied patterns of DNA sequence variation and evolution for 22 genes
      located on the neo-X and neo-Y chromosomes of Drosophila miranda. As found
      previously, nucleotide site diversity is greatly reduced on the neo-Y chromosome,
      with a severely distorted frequency spectrum. There is also an accelerated rate
      of amino-acid sequence evolution on the neo-Y chromosome. Comparisons of
      nonsynonymous and silent variation and divergence suggest that amino-acid
      sequences on the neo-X chromosome are subject to purifying selection, whereas
      this is much weaker on the neo-Y. The same applies to synonymous variants
      affecting codon usage. There is also an indication of a recent relaxation of
      selection on synonymous mutations for genes on other chromosomes. Genes that are
      weakly expressed on the neo-Y chromosome appear to have a faster rate of
      accumulation of both nonsynonymous and unpreferred synonymous mutations than
      genes with high levels of expression, although the rate of accumulation when both
      types of mutation are pooled is higher for the neo-Y chromosome than for the neo
      X chromosome even for highly expressed genes.

PMID- 17028323
TI  - Duplication of centromeric histone H3 (HTR12) gene in Arabidopsis halleri and A.
      lyrata, plant species with multiple centromeric satellite sequences.
AB  - Arabidopsis halleri and lyrata have three different major centromeric satellite
      sequences, a unique finding for a diploid Arabidopsis species. Since centromeric
      histones coevolve with centromeric satellites, these proteins would be predicted
      to show signs of selection when new centromere satellites have recently arisen.
      We isolated centromeric protein genes from A. halleri and lyrata and found that
      one of them, HTR12 (CENP-A), is duplicated, while CENP-C is not. Phylogenetic
      analysis indicates that the HTR12 duplication occurred after these species
      diverged from A. thaliana. Genetic mapping shows that HTR12 copy B has the same
      genomic location as the A. thaliana gene; the other copy (A, at the other end of
      the same chromosome) is probably the new copy. To test for selection since the
      duplication, we surveyed diversity at both HTR12 loci within A. lyrata. Overall,
      there is no strong evidence for an "evolutionary arms race" causing multiple
      replacement substitutions. The A. lyrata HTR12B sequences fall into three classes
      of haplotypes, apparently maintained for a long time, but they all encode the
      same amino acid sequence. In contrast, HTR12A has low diversity, but many
      variants are amino acid replacements, possibly due to independent selective
      sweeps within populations of the species.

PMID- 17028325
TI  - The maintenance of sex in bacteria is ensured by its potential to reload genes.
AB  - Why sex is maintained in nature is a fundamental question in biology. Natural
      genetic transformation (NGT) is a sexual process by which bacteria actively take
      up exogenous DNA and use it to replace homologous chromosomal sequences. As it
      has been demonstrated, the role of NGT in repairing deleterious mutations under
      constant selection is insufficient for its survival, and the lack of other viable
      explanations have left no alternative except that DNA uptake provides nucleotides
      for food. Here we develop a novel simulation approach for the long-term dynamics
      of genome organization (involving the loss and acquisition of genes) in a
      bacterial species consisting of a large number of spatially distinct populations
      subject to independently fluctuating ecological conditions. Our results show that
      in the presence of weak interpopulation migration NGT is able to subsist as a
      mechanism to reload locally lost, intermittently selected genes from the
      collective gene pool of the species through DNA uptake from migrants. Reloading
      genes and combining them with those in locally adapted genomes allow individual
      cells to readapt faster to environmental changes. The machinery of transformation
      survives under a wide range of model parameters readily encompassing real-world
      biological conditions. These findings imply that the primary role of NGT is not
      to serve the cell with food, but to provide homologous sequences for restoring
      genes that have disappeared from or become degraded in the local population.

PMID- 17028324
TI  - A point mutation in the Aspergillus nidulans sonBNup98 nuclear pore complex gene
      causes conditional DNA damage sensitivity.
AB  - The nuclear pore complex (NPC) is embedded in the nuclear envelope where it
      mediates transport between the cytoplasm and nucleus and helps to organize
      nuclear architecture. We previously isolated sonB1, a mutation encoding a single
      amino acid substitution within the Aspergillus nidulans SONBnNup98 NPC protein
      (nucleoporin). Here we demonstrate that this mutation causes marked DNA damage
      sensitivity at 42 degrees . Although SONBnNup98 has roles in the G2 transition,
      we demonstrate that the G2 DNA damage checkpoint is functional in the sonB1
      mutant at 42 degrees . The MRN complex is composed of MRE11, RAD50, and NBS1 and
      functions in checkpoint signaling, DNA repair, and telomere maintenance. At 42
      degrees we find that the DNA damage response defect of sonB1 mutants causes
      synthetic lethality when combined with mutations in scaANBS1, the A. nidulans
      homolog of NBS1. We provide evidence that this synthetic lethality is independent
      of MRN cell cycle checkpoint functions or MREAMRE11-mediated DNA repair
      functions. We also demonstrate that the single A. nidulans histone H2A gene
      contains the C-terminal SQE motif of histone H2AX isoforms and that this motif is
      required for the DNA damage response. We propose that the sonB1 nucleoporin
      mutation causes a defect in a novel part of the DNA damage response.

PMID- 17028326
TI  - Effect of the major repeat sequence on mitotic recombination in Candida albicans.
AB  - The major repeat sequence (MRS) is known to play a role in karyotypic variation
      in Candida albicans. The MRS affects karyotypic variation by expanding and
      contracting internal repeats, by altering the frequency of chromosome loss, and
      by serving as a hotspot for chromosome translocation. We proposed that the
      effects of the MRS on translocation could be better understood by examination of
      the effect of the MRS on a similar event, mitotic recombination between two
      chromosome homologs. We examined the frequency of mitotic recombination across an
      MRS of average size (approximately 50 kb) as well as the rate of recombination in
      a 325-kb stretch of DNA adjacent to the MRS. Our results indicate that mitotic
      recombination frequencies across the MRS were not enhanced compared to the
      frequencies measured across the 325-kb region adjacent to the MRS. Mitotic
      recombination events were found to occur throughout the 325-kb region analyzed as
      well as within the MRS itself. This analysis of mitotic recombination frequencies
      across a large portion of chromosome 5 is the first large-scale analysis of
      mitotic recombination done in C. albicans and indicates that mitotic
      recombination frequencies are similar to the rates found in Saccharomyces
      cerevisiae.

PMID- 17028328
TI  - Functional characterization of Drosophila Translin and Trax.
AB  - The vertebrate RNA and ssDNA-binding protein Translin has been suggested to
      function in a variety of cellular processes, including DNA damage response, RNA
      transport, and translational control. The Translin-associated factor X (Trax)
      interacts with Translin, and Trax protein stability depends on the presence of
      Translin. To determine the function of the Drosophila Translin and Trax, we
      generated a translin null mutant and isolated a trax nonsense mutation. translin
      and trax single and double mutants are viable, fertile, and phenotypically
      normal. Meiotic recombination rates and chromosome segregation are also not
      affected in translin and trax mutants. In addition, we found no evidence for an
      increased sensitivity for DNA double-strand damage in embryos and developing
      larvae. Together with the lack of evidence for their involvement in DNA double
      strand break checkpoints, this argues against a critical role for Translin and
      Trax in sensing or repairing such DNA damage. However, Drosophila translin is
      essential for stabilizing the Translin interaction partner Trax, a function that
      is surprisingly conserved throughout evolution. Conversely, trax is not essential
      for Translin stability as trax mutants exhibit normal levels of Translin protein.

PMID- 17028327
TI  - The histone deubiquitinating enzyme Ubp10 is involved in rDNA locus control in
      Saccharomyces cerevisiae by affecting Sir2p association.
AB  - Histone modifications influence chromatin structure and thus regulate the
      accessibility of DNA to replication, recombination, repair, and transcription. We
      show here that the histone deubiquitinating enzyme Ubp10 contributes to the
      formation/maintenance of silenced chromatin at the rDNA by affecting Sir2p
      association.

PMID- 17028329
TI  - Molecular diversity after a range expansion in heterogeneous environments.
AB  - Recent range expansions have probably occurred in many species, as they often
      happen after speciation events, after ice ages, or after the introduction of
      invasive species. While it has been shown that range expansions lead to patterns
      of molecular diversity distinct from those of a pure demographic expansion, the
      fact that many species do live in heterogeneous environments has not been taken
      into account. We develop here a model of range expansion with a spatial
      heterogeneity of the environment, which is modeled as a gamma distribution of the
      carrying capacities of the demes. By allowing temporal variation of these
      carrying capacities, our model becomes a new metapopulation model linking
      ecological parameters to molecular diversity. We show by extensive simulations
      that environmental heterogeneity induces a loss of genetic diversity within demes
      and increases the degree of population differentiation. We find that
      metapopulations with low average densities are much more affected by
      environmental heterogeneity than metapopulations with high average densities,
      which are relatively insensitive to spatial and temporal variations of the
      environment. Spatial heterogeneity is shown to have a larger impact on genetic
      diversity than temporal heterogeneity. Overall, temporal heterogeneity and local
      extinctions are not found to leave any specific signature on molecular diversity
      that cannot be produced by spatial heterogeneity.

PMID- 17028330
TI  - Phylogenetic analysis of fungal centromere H3 proteins.
AB  - Centromere H3 proteins (CenH3's) are variants of histone H3 specialized for
      packaging centromere DNA. Unlike canonical H3, which is among the most conserved
      of eukaryotic proteins, CenH3's are rapidly evolving, raising questions about
      orthology and conservation of function across species. To gain insight on CenH3
      evolution and function, a phylogenetic analysis was undertaken on CenH3 proteins
      drawn from a single, ancient lineage, the Fungi. Using maximum-likelihood
      methods, a credible phylogeny was derived for the conserved histone fold domain
      (HFD) of 25 fungal CenH3's. The collection consisted mostly of hemiascomycetous
      yeasts, but also included basidiomycetes, euascomycetes, and an archaeascomycete.
      The HFD phylogeny closely recapitulated known evolutionary relationships between
      the species, supporting CenH3 orthology. The fungal CenH3's lacked significant
      homology in their N termini except for those of the Saccharomyces/Kluyveromyces
      clade that all contained a region homologous to the essential N-terminal domain
      found in Saccharomyces cerevisiae Cse4. The ability of several heterologous
      CenH3's to function in S. cerevisiae was tested and found to correlate with
      evolutionary distance. Domain swapping between S. cerevisiae Cse4 and the
      noncomplementing Pichia angusta ortholog showed that species specificity could
      not be explained by the presence or absence of any recognized secondary
      structural element of the HFD.

PMID- 17028331
TI  - Selection, recombination and demographic history in Drosophila miranda.
AB  - Selection, recombination, and the demographic history of a species can all have
      profound effects on genomewide patterns of variability. To assess the impact of
      these forces in the genome of Drosophila miranda, we examine polymorphism and
      divergence patterns at 62 loci scattered across the genome. In accordance with
      recent findings in D. melanogaster, we find that noncoding DNA generally evolves
      more slowly than synonymous sites, that the distribution of polymorphism
      frequencies in noncoding DNA is significantly skewed toward rare variants
      relative to synonymous sites, and that long introns evolve significantly slower
      than short introns or synonymous sites. These observations suggest that most
      noncoding DNA is functionally constrained and evolving under purifying selection.
      However, in contrast to findings in the D. melanogaster species group, we find
      little evidence of adaptive evolution acting on either coding or noncoding
      sequences in D. miranda. Levels of linkage disequilibrium (LD) in D. miranda are
      comparable to those observed in D. melanogaster, but vary considerably among
      chromosomes. These patterns suggest a significantly lower rate of recombination
      on autosomes, possibly due to the presence of polymorphic autosomal inversions
      and/or differences in chromosome sizes. All chromosomes show significant
      departures from the standard neutral model, including too much heterogeneity in
      synonymous site polymorphism relative to divergence among loci and a general
      excess of rare synonymous polymorphisms. These departures from neutral
      equilibrium expectations are discussed in the context of nonequilibrium models of
      demography and selection.

PMID- 17028332
TI  - The transposable element landscape of the model legume Lotus japonicus.
AB  - The largest component of plant and animal genomes characterized to date is
      transposable elements (TEs). The availability of a significant amount of Lotus
      japonicus genome sequence has permitted for the first time a comprehensive study
      of the TE landscape in a legume species. Here we report the results of a combined
      computer-assisted and experimental analysis of the TEs in the 32.4 Mb of finished
      TAC clones. While computer-assisted analysis facilitated a determination of TE
      abundance and diversity, the availability of complete TAC sequences permitted
      identification of full-length TEs, which facilitated the design of tools for
      genomewide experimental analysis. In addition to containing all TE types found in
      previously characterized plant genomes, the TE component of L. japonicus
      contained several surprises. First, it is the second species (after Oryza sativa)
      found to be rich in Pack-MULEs, with >1000 elements that have captured and
      amplified gene fragments. In addition, we have identified what appears to be a
      legume-specific MULE family that was previously identified only in fungal
      species. Finally, the L. japonicus genome contains many hundreds, perhaps
      thousands of Sireviruses: Ty1/copia-like elements with an extra ORF.
      Significantly, several of the L. japonicus Sireviruses have recently amplified
      and may still be actively transposing.

PMID- 17028334
TI  - The distribution of beneficial mutant effects under strong selection.
AB  - For a general theory of adaptation, it is essential to know the distribution of
      fitness effects of beneficial mutations. Recent theoretical and empirical studies
      have made considerable progress in determining the characteristics of this
      distribution. To date, the experiments have largely verified the theoretical
      predictions. Despite the fact that the theoretical work has assumed small
      selection coefficients, strong selection has been observed in some experiments,
      especially those involving novel environments. Here, we derive the distribution
      of fitness effects among fixed beneficial mutants without the restriction of low
      selection coefficients. The fate of strongly favored alleles is less affected by
      stochastic drift while rare, causing the distribution of fitness effects among
      fixed beneficial mutations to reflect more closely the distribution among all
      newly arising beneficial mutations. We also find that when many alleles compete
      for fixation within an asexual population (clonal interference), the beneficial
      effects of a newly fixed mutant cannot be well estimated because of the high
      number of subsequent mutations that arise within the genome, regardless of
      whether selection is strong or weak.

PMID- 17028333
TI  - Testing chromosomal phylogenies and inversion breakpoint reuse in Drosophila.
AB  - A combination of cytogenetic and bioinformatic procedures was used to test the
      chromosomal phylogeny relating Drosophila buzzatii with D. repleta. Chromosomes X
      and 2, harboring most of the inversions fixed between these two species, were
      analyzed. First, chromosomal segments conserved during the divergence of the two
      species were identified by comparative in situ hybridization to the D. repleta
      chromosomes of 180 BAC clones from a BAC-based physical map of the D. buzzatii
      genome. These conserved segments were precisely delimited with the aid of clones
      containing inversion breakpoints. Then GRIMM software was used to estimate the
      minimum number of rearrangements necessary to transform one genome into the other
      and identify all possible rearrangement scenarios. Finally, the most plausible
      inversion trajectory was tested by hybridizing 12 breakpoint-bearing BAC clones
      to the chromosomes of seven other species in the repleta group. The results show
      that chromosomes X and 2 of D. buzzatii and D. repleta differ by 12 paracentric
      inversions. Nine of them are fixed in chromosome 2 and entail two breakpoint
      reuses. Our results also show that the cytological relationship between D.
      repleta and D. mercatorum is closer than that between D. repleta and D.
      peninsularis, and we propose that the phylogenetic relationships in this lineage
      of the repleta group be reconsidered. We also estimated the rate of rearrangement
      between D. repleta and D. buzzatii and conclude that rates within the genus
      Drosophila vary substantially between lineages, even within a single species
      group.

PMID- 17028335
TI  - On the generalized poisson regression mixture model for mapping quantitative
      trait loci with count data.
AB  - Statistical methods for mapping quantitative trait loci (QTL) have been
      extensively studied. While most existing methods assume normal distribution of
      the phenotype, the normality assumption could be easily violated when phenotypes
      are measured in counts. One natural choice to deal with count traits is to apply
      the classical Poisson regression model. However, conditional on covariates, the
      Poisson assumption of mean-variance equality may not be valid when data are
      potentially under- or overdispersed. In this article, we propose an interval
      mapping approach for phenotypes measured in counts. We model the effects of QTL
      through a generalized Poisson regression model and develop efficient likelihood
      based inference procedures. This approach, implemented with the EM algorithm,
      allows for a genomewide scan for the existence of QTL throughout the entire
      genome. The performance of the proposed method is evaluated through extensive
      simulation studies along with comparisons with existing approaches such as the
      Poisson regression and the generalized estimating equation approach. An
      application to a rice tiller number data set is given. Our approach provides a
      standard procedure for mapping QTL involved in the genetic control of complex
      traits measured in counts.

PMID- 17028336
TI  - Substitution mapping in dahl rats identifies two distinct blood pressure
      quantitative trait loci within 1.12- and 1.25-mb intervals on chromosome 3.
AB  - Substitution mapping was used to refine the localization of blood pressure (BP)
      quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located
      at the q terminus of rat chromosome 3 (RNO3). An F2(SxS.R-Edn3) population
      (n=173) was screened to identify rats having crossovers within the congenic
      region of RNO3 and six congenic substrains were developed that carry shorter
      segments of R-rat-derived RNO3. Five of the six congenic substrains had
      significantly lower BP compared to the parental S rat. The lack of BP lowering
      effect demonstrated by the S.R(ET3x5) substrain and the BP lowering effect
      retained by the S.R(ET3x2) substrain together define the RNO3 BP QTL-containing
      region as approximately 4.64 Mb. Two nonoverlapping substrains, S.R(ET3x1) and
      S.R(ET3x6), had significantly lower BP compared to the S strain, indicating the
      presence of two distinct BP QTL in the RNO3 q terminus. The RNO3 q terminus was
      fine mapped with newly developed polymorphic markers to characterize the extent
      of the congenic regions. The two RNO3 BP QTL regions were thus defined as within
      intervals of 0.05-1.12 and 0.72-1.25 Mb, respectively. Also important was our
      difficulty in fine mapping and marker placement in this portion of the rat genome
      (and thus candidate gene identification) using the available genomic data,
      including the rat genome sequence.

PMID- 17028337
TI  - Structure-function analysis of delta trafficking, receptor binding and signaling
      in Drosophila.
AB  - The transmembrane proteins Delta and Notch act as ligand and receptor in a
      conserved signaling pathway required for a variety of cell fate specification
      events in many organisms. Binding of Delta to Notch results in a proteolytic
      cascade that releases the Notch intracellular domain, allowing it to participate
      in transcriptional activation in the nucleus. Recent research has implicated the
      endocytic and ubiquitylation machinery as essential components of Delta-Notch
      signaling. Our analysis of chimeric and missense Delta variants has delineated a
      number of structural requirements for Delta trafficking, receptor binding, and
      signaling. We find that while the Delta N-terminal domain is necessary and
      sufficient for binding to Notch, the integrity of the epidermal-growth-factor
      like repeat (ELR) 2 is also required for Notch binding. Screening of 117 Delta
      mutant lines for proteins that exhibit aberrant subcellular trafficking has led
      to the identification of 18 Delta alleles (DlTD alleles) that encode "trafficking
      defective" Delta proteins. We find, unexpectedly, that many DlTD alleles contain
      missense mutations in ELRs within the Delta extracellular domain. Finally, we
      find that two DlTD alleles contain lysine missense mutations within the Delta
      intracellular domain (DeltaICD) that may identify residues important for DeltaICD
      mono-ubiquitylation and subsequent Delta endocytosis and signaling.

PMID- 17028338
TI  - The association among gene expression responses to nine abiotic stress treatments
      in Arabidopsis thaliana.
AB  - The identification and analysis of genes exhibiting large expression responses to
      several different types of stress may provide insights into the functional basis
      of multiple stress tolerance in plant species. This study considered whole-genome
      transcriptional profiles from Arabidopsis thaliana root and shoot organs under
      nine abiotic stress conditions (cold, osmotic stress, salt, drought, genotoxic
      stress, ultraviolet light, oxidative stress, wounding, and high temperature) and
      at six different time points of stress exposure (0.5, 1, 3, 6, 12, and 24 hr). In
      roots, genomewide correlations between transcriptional responses to different
      stress treatments peaked following 1 hr of stress exposure, while in shoots,
      correlations tended to increase following 6 hr of stress exposure. The generality
      of stress responses at the transcriptional level was therefore time and organ
      dependent. A total of 67 genes were identified as exhibiting a statistically
      significant pattern of gene expression characterized by large transcriptional
      responses to all nine stress treatments. Most genes were identified from early to
      middle (1-6 hr) time points of stress exposure. Analysis of this gene set
      indicated that cell rescue/defense/virulence, energy, and metabolism functional
      classes were overrepresented, providing novel insight into the functional basis
      of multiple stress tolerance in Arabidopsis.

PMID- 17028339
TI  - Association mapping of complex trait loci with context-dependent effects and
      unknown context variable.
AB  - A novel method for Bayesian analysis of genetic heterogeneity and multilocus
      association in random population samples is presented. The method is valid for
      quantitative and binary traits as well as for multiallelic markers. In the
      method, individuals are stochastically assigned into two etiological groups that
      can have both their own, and possibly different, subsets of trait-associated
      (disease-predisposing) loci or alleles. The method is favorable especially in
      situations when etiological models are stratified by the factors that are unknown
      or went unmeasured, that is, if genetic heterogeneity is due to, for example,
      unknown genes x environment or genes x gene interactions. Additionally, a
      heterogeneity structure for the phenotype does not need to follow the structure
      of the general population; it can have a distinct selection history. The
      performance of the method is illustrated with simulated example of genes x
      environment interaction (quantitative trait with loosely linked markers) and
      compared to the results of single-group analysis in the presence of missing data.
      Additionally, example analyses with previously analyzed cystic fibrosis and type
      2 diabetes data sets (binary traits with closely linked markers) are presented.
      The implementation (written in WinBUGS) is freely available for research purposes
      from http://www.rni.helsinki.fi/ approximately mjs/.

PMID- 17028340
TI  - The X chromosome in quantitative trait locus mapping.
AB  - The X chromosome requires special treatment in the mapping of quantitative trait
      loci (QTL). However, most QTL mapping methods, and most computer programs for QTL
      mapping, have focused exclusively on autosomal loci. We describe a method for
      appropriate treatment of the X chromosome for QTL mapping in experimental
      crosses. We address the important issue of formulating the null hypothesis of no
      linkage appropriately. If the X chromosome is treated like an autosome, a sex
      difference in the phenotype can lead to spurious linkage on the X chromosome.
      Further, the number of degrees of freedom for the linkage test may be different
      for the X chromosome than for autosomes, and so an X chromosome-specific
      significance threshold is required. To address this issue, we propose a general
      procedure to obtain chromosome-specific significance thresholds that controls the
      genomewide false positive rate at the desired level. We apply our methods to data
      on gut length in a large intercross of mice carrying the Sox10Dom mutation, a
      model of Hirschsprung disease. We identified QTL contributing to variation in gut
      length on chromosomes 5 and 18. We found suggestive evidence of linkage to the X
      chromosome, which would be viewed as strong evidence of linkage if the X
      chromosome was treated as an autosome. Our methods have been implemented in the
      package R/qtl.

PMID- 17028341
TI  - An Arabidopsis basic helix-loop-helix leucine zipper protein modulates metal
      homeostasis and auxin conjugate responsiveness.
AB  - The plant hormone auxin can be regulated by formation and hydrolysis of amide
      linked indole-3-acetic acid (IAA) conjugates. Here, we report the
      characterization of the dominant Arabidopsis iaa-leucine resistant3 (ilr3-1)
      mutant, which has reduced sensitivity to IAA-Leu and IAA-Phe, while retaining
      wild-type responses to free IAA. The gene defective in ilr3-1 encodes a basic
      helix-loop-helix leucine zipper protein, bHLH105, and the ilr3-1 lesion results
      in a truncated product. Overexpressing ilr3-1 in wild-type plants recapitulates
      certain ilr3-1 mutant phenotypes. In contrast, the loss-of-function ilr3-2 allele
      has increased IAA-Leu sensitivity compared to wild type, indicating that the ilr3
      1 allele confers a gain of function. Microarray and quantitative real-time PCR
      analyses revealed five downregulated genes in ilr3-1, including three encoding
      putative membrane proteins similar to the yeast iron and manganese transporter
      Ccc1p. Transcript changes are accompanied by reciprocally misregulated metal
      accumulation in ilr3-1 and ilr3-2 mutants. Further, ilr3-1 seedlings are less
      sensitive than wild type to manganese, and auxin conjugate response phenotypes
      are dependent on exogenous metal concentration in ilr3 mutants. These data
      suggest a model in which the ILR3/bHLH105 transcription factor regulates
      expression of metal transporter genes, perhaps indirectly modulating IAA
      conjugate hydrolysis by controlling the availability of metals previously shown
      to influence IAA-amino acid hydrolase protein activity.

PMID- 17028343
TI  - Dynamic genetic interactions determine odor-guided behavior in Drosophila
      melanogaster.
AB  - Understanding the genetic architecture of complex traits requires identification
      of the underlying genes and characterization of gene-by-gene and genotype-by
      environment interactions. Behaviors that mediate interactions between organisms
      and their environment are complex traits expected to be especially sensitive to
      environmental conditions. Previous studies on the olfactory avoidance response of
      Drosophila melanogaster showed that the genetic architecture of this model
      behavior depends on epistatic networks of pleiotropic genes. We performed a
      screen of 1339 co-isogenic p[GT1]-element insertion lines to identify novel genes
      that contribute to odor-guided behavior and identified 55 candidate genes with
      known p[GT1]-element insertion sites. Characterization of the expression profiles
      of 10 p[GT1]-element insertion lines showed that the effects of the transposon
      insertions are often dependent on developmental stage and that hypomorphic
      mutations in developmental genes can elicit profound adult behavioral deficits.
      We assessed epistasis among these genes by constructing all possible double
      heterozygotes and measuring avoidance responses under two stimulus conditions. We
      observed enhancer and suppressor effects among subsets of these P-element-tagged
      genes, and surprisingly, epistatic interactions shifted with changes in the
      concentration of the olfactory stimulus. Our results show that the manifestation
      of epistatic networks dynamically changes with alterations in the environment.

PMID- 17028342
TI  - Types and rates of sequence evolution at the high-molecular-weight glutenin locus
      in hexaploid wheat and its ancestral genomes.
AB  - The Glu-1 locus, encoding the high-molecular-weight glutenin protein subunits,
      controls bread-making quality in hexaploid wheat (Triticum aestivum) and
      represents a recently evolved region unique to Triticeae genomes. To understand
      the molecular evolution of this locus region, three orthologous Glu-1 regions
      from the three subgenomes of a single hexaploid wheat species were sequenced,
      totaling 729 kb of sequence. Comparing each Glu-1 region with its corresponding
      homologous region from the D genome of diploid wheat, Aegilops tauschii, and the
      A and B genomes of tetraploid wheat, Triticum turgidum, revealed that, in
      addition to the conservation of microsynteny in the genic regions, sequences in
      the intergenic regions, composed of blocks of nested retroelements, are also
      generally conserved, although a few nonshared retroelements that differentiate
      the homologous Glu-1 regions were detected in each pair of the A and D genomes.
      Analysis of the indel frequency and the rate of nucleotide substitution, which
      represent the most frequent types of sequence changes in the Glu-1 regions,
      demonstrated that the two A genomes are significantly more divergent than the two
      B genomes, further supporting the hypothesis that hexaploid wheat may have more
      than one tetraploid ancestor.

PMID- 17028344
TI  - The Cdc34/SCF ubiquitination complex mediates Saccharomyces cerevisiae cell wall
      integrity.
AB  - To identify novel functions for the Cdc34/SCF ubiquitination complex, we analyzed
      genomewide transcriptional profiles of cdc53-1 and cdc34-2 Saccharomyces
      cerevisiae mutants. This analysis revealed altered expression for several gene
      families, including genes involved in the regulation of cell wall organization
      and biosynthesis. This led us to uncover a role for the Cdc34/SCF complex in the
      regulation of cell wall integrity. In support of this, cdc53-1 and cdc34-2
      mutants exhibit phenotypes characteristic of cell wall integrity mutants, such as
      SDS sensitivity and temperature-sensitive suppression by osmotic stabilizers.
      Examination of these mutants revealed defects in their induction of Slt2
      phosphorylation, indicating defects in Pkc1-Slt2 MAPK signaling. Consistent with
      this, synthetic genetic interactions were observed between the genes encoding the
      Cdc34/SCF complex and key components of the Pck1-Slt2 MAPK pathway. Further
      analysis revealed that Cdc34/SCF mutants have reduced levels of active Rho1,
      suggesting that these defects stem from the deregulated activity of the Rho1
      GTPase. Altering the activity of Rho1 via manipulation of the Rho1-GAPs LRG1 or
      SAC7 affected Cdc34/SCF mutant growth. Strikingly, however, deletion of LRG1
      rescued the growth defects associated with Cdc34/SCF mutants, whereas deletion of
      SAC7 enhanced these defects. Given the differential roles that these GAPs play in
      the regulation of Rho1, these observations indicate the importance of
      coordinating Cdc34/SCF activity with specific Rho1 functions.

PMID- 17028345
TI  - Centromere-proximal crossovers are associated with precocious separation of
      sister chromatids during meiosis in Saccharomyces cerevisiae.
AB  - In most organisms, meiotic chromosome segregation is dependent on crossovers
      (COs), which enable pairs of homologous chromosomes to segregate to opposite
      poles at meiosis I. In mammals, the majority of meiotic chromosome segregation
      errors result from a lack of COs between homologs. Observations in Homo sapiens
      and Drosophila melanogaster have revealed a second class of exceptional events in
      which a CO occurred near the centromere of the missegregated chromosome. We show
      that in wild-type strains of Saccharomyces cerevisiae, most spore inviability is
      due to precocious separation of sister chromatids (PSSC) and that PSSC is often
      associated with centromere-proximal crossing over. COs, as opposed to
      nonreciprocal recombination events (NCOs), are preferentially associated with
      missegregation. Strains mutant for the RecQ homolog, SGS1, display reduced spore
      viability and increased crossing over. Much of the spore inviability in sgs1
      results from PSSC, and these events are often associated with centromere-proximal
      COs, just as in wild type. When crossing over in sgs1 is reduced by the
      introduction of a nonnull allele of SPO11, spore viability is improved,
      suggesting that the increased PSSC is due to increased crossing over. We present
      a model for PSSC in which a centromere-proximal CO promotes local loss of sister
      chromatid cohesion.

PMID- 17028346
TI  - Statistical epistasis is a generic feature of gene regulatory networks.
AB  - Functional dependencies between genes are a defining characteristic of gene
      networks underlying quantitative traits. However, recent studies show that the
      proportion of the genetic variation that can be attributed to statistical
      epistasis varies from almost zero to very high. It is thus of fundamental as well
      as instrumental importance to better understand whether different functional
      dependency patterns among polymorphic genes give rise to distinct statistical
      interaction patterns or not. Here we address this issue by combining a
      quantitative genetic model approach with genotype-phenotype models capable of
      translating allelic variation and regulatory principles into phenotypic variation
      at the level of gene expression. We show that gene regulatory networks with and
      without feedback motifs can exhibit a wide range of possible statistical genetic
      architectures with regard to both type of effect explaining phenotypic variance
      and number of apparent loci underlying the observed phenotypic effect. Although
      all motifs are capable of harboring significant interactions, positive feedback
      gives rise to higher amounts and more types of statistical epistasis. The results
      also suggest that the inclusion of statistical interaction terms in genetic
      models will increase the chance to detect additional QTL as well as functional
      dependencies between genetic loci over a broad range of regulatory regimes. This
      article illustrates how statistical genetic methods can fruitfully be combined
      with nonlinear systems dynamics to elucidate biological issues beyond reach of
      each methodology in isolation.

PMID- 17028347
TI  - Molecular analysis, cytogenetics and fertility of introgression lines from
      transgenic wheat to Aegilops cylindrica host.
AB  - Natural hybridization and backcrossing between Aegilops cylindrica and Triticum
      aestivum can lead to introgression of wheat DNA into the wild species. Hybrids
      between Ae. cylindrica and wheat lines bearing herbicide resistance (bar),
      reporter (gus), fungal disease resistance (kp4), and increased insect tolerance
      (gna) transgenes were produced by pollination of emasculated Ae. cylindrica
      plants. F1 hybrids were backcrossed to Ae. cylindrica under open-pollination
      conditions, and first backcrosses were selfed using pollen bags. Female fertility
      of F1 ranged from 0.03 to 0.6%. Eighteen percent of the sown BC1s germinated and
      flowered. Chromosome numbers ranged from 30 to 84 and several of the plants bore
      wheat-specific sequence-characterized amplified regions (SCARs) and the bar gene.
      Self fertility in two BC1 plants was 0.16 and 5.21%, and the others were
      completely self-sterile. Among 19 BC1S1 individuals one plant was transgenic, had
      43 chromosomes, contained the bar gene, and survived glufosinate treatments. The
      other BC1S1 plants had between 28 and 31 chromosomes, and several of them carried
      SCARs specific to wheat A and D genomes. Fertility of these plants was higher
      under open-pollination conditions than by selfing and did not necessarily
      correlate with even or euploid chromosome number. Some individuals having
      supernumerary wheat chromosomes recovered full fertility.

PMID- 17028348
TI  - Functional analysis of genes differentially expressed in the Drosophila wing
      disc: role of transcripts enriched in the wing region.
AB  - Differential gene expression is the major mechanism underlying the development of
      specific body regions. Here we assessed the role of genes differentially
      expressed in the Drosophila wing imaginal disc, which gives rise to two distinct
      adult structures: the body wall and the wing. Reverse genetics was used to test
      the function of uncharacterized genes first identified in a microarray screen as
      having high levels of expression in the presumptive wing. Such genes could
      participate in elaborating the specific morphological characteristics of the
      wing. The activity of the genes was modulated using misexpression and RNAi
      mediated silencing. Misexpression of eight of nine genes tested caused
      phenotypes. Of 12 genes tested, 10 showed effective silencing with RNAi
      transgenes, but only 3 of these had resulting phenotypes. The wing phenotypes
      resulting from RNAi suggest that CG8780 is involved in patterning the veins in
      the proximal region of the wing blade and that CG17278 and CG30069 are required
      for adhesion of wing surfaces. Venation and apposition of the wing surfaces are
      processes specific to wing development providing a correlation between the
      expression and function of these genes. The results show that a combination of
      expression profiling and tissue-specific gene silencing has the potential to
      identify new genes involved in wing development and hence to contribute to our
      understanding of this process. However, there are both technical and biological
      limitations to this approach, including the efficacy of RNAi and the role that
      gene redundancy may play in masking phenotypes.

PMID- 17028350
TI  - Prevention of medication error and unintentional drug poisoning in the elderly.

PMID- 17028349
TI  - Reduced dosage of pos-1 suppresses Mex mutants and reveals complex interactions
      among CCCH zinc-finger proteins during Caenorhabditis elegans embryogenesis.
AB  - Cell fate specification in the early C. elegans embryo requires the activity of a
      family of proteins with CCCH zinc-finger motifs. Two members of the family, MEX-5
      and MEX-6, are enriched in the anterior of the early embryo where they inhibit
      the accumulation of posterior proteins. Embryos from mex-5 single-mutant mothers
      are inviable due to the misexpression of SKN-1, a transcription factor that can
      specify mesoderm and endoderm. The aberrant expression of SKN-1 causes a loss of
      hypodermal and neuronal tissue and an excess of pharyngeal muscle, a Mex
      phenotype (muscle excess). POS-1, a third protein with CCCH motifs, is
      concentrated in the posterior of the embryo where it restricts the expression of
      at least one protein to the anterior. We discovered that reducing the dosage of
      pos-1(+) can suppress the Mex phenotype of mex-5(-) embryos and that POS-1 binds
      the 3'-UTR of mex-6. We propose that the suppression of the Mex phenotype by
      reducing pos-1(+) is due to decreased repression of mex-6 translation. Our
      detailed analyses of these protein functions reveal complex interactions among
      the CCCH finger proteins and suggest that their complementary expression patterns
      might be refined by antagonistic interactions among them.

PMID- 17028351
TI  - Drug-induced hypoglycaemia--new insight into an old problem.
AB  - OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not
      taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional
      hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced
      hypoglycaemia without a known history of exposure to hypoglycaemic agents,
      referred to the Hospital Authority Toxicology Reference Laboratory from June 2005
      to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases,
      laboratory findings, possible causes, age distribution, and final outcomes.
      RESULTS: A total of 51 such patients were referred, in whom the presence of oral
      hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23
      patients, oral hypoglycaemic agents could only be detected by target analysis,
      not through broad-spectrum screening. Gliclazide and glibenclamide were detected
      in 14 and eight patients respectively, whereas glimepiride, nateglinide and
      rosiglitazone were detected in the remaining patient. Possible sources of oral
      hypoglycaemic agents included drug administration errors in residential care
      homes for the elderly (n=9), mistakenly taking medication of a family member or
      employer (n=6), taking stock medication by mistake (n=2), taking Chinese
      proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking
      unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding
      these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered
      uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral
      hypoglycaemic agents is a recognised problem, particularly in cases where family
      members living in the same household are taking similar medications. Possible
      drug administration errors in residential care homes for the elderly should be
      investigated, and procedures rectified if confirmed. Health care providers should
      be vigilant to such potential errors, especially in cases of unexplained
      hypoglycaemia.

PMID- 17028352
TI  - Twelve years' local experience in ambulatory anaesthesia.
AB  - OBJECTIVES: To determine the incidence of adverse events after ambulatory
      anaesthesia (postoperative nausea and vomiting, postoperative pain, difficulty in
      movement), and to evaluate the level of satisfaction of patients with our
      service. DESIGN: Retrospective study with questionnaire survey. SETTING: Tertiary
      referral centre, Hong Kong. PARTICIPANTS: All patients whose duly completed
      questionnaires were available. MAIN OUTCOME MEASURES: Incidence of adverse events
      and level of patient satisfaction. RESULTS: A total of 9197 patients underwent
      surgery under general anaesthesia or neuraxial blockade by anaesthetists in
      ambulatory settings from October 1993 to December 2005: questionnaires filled out
      by 8231 of these patients were analysed, whereas 549 questionnaires were lost,
      and 417 patients could not be contacted. The response rate was 90%; 59% of the
      respondents were males, 50% were younger than 15 years and 5% older than 60
      years. Fifty-one percent of surgery with anaesthetists' involvement was performed
      under general anaesthesia and 48.9% under general anaesthesia and regional blocks
      and 0.1% under neuraxial blockade. There were 3.3% of patients experienced
      postoperative nausea and vomiting, 60.2% experienced episodes of pain between the
      time of discharge and the time of interview, and 46% required analgesics.
      Nonetheless, 80% resumed normal activities within 5 hours after anaesthesia and
      97.5% resumed normal diet the following morning. Over 99% rated our service as
      good or excellent. CONCLUSION: Although ambulatory anaesthesia was associated
      with minor adverse events, patients could resume normal diet and daily activities
      quickly and were satisfied with the service.

PMID- 17028353
TI  - Sublingual misoprostol compared to artificial rupture of membranes plus oxytocin
      infusion for labour induction in nulliparous women with a favourable cervix at
      term.
AB  - OBJECTIVES: To compare the efficacy of labour induction using sublingual
      misoprostol versus combined artificial rupture of membranes and oxytocin infusion
      for nulliparous women with a favourable cervix at term. DESIGN: Open randomised
      controlled trial. SETTING: Regional hospital, Hong Kong. PATIENTS: Fifty
      nulliparous women with a favourable cervix (Bishop score 6 or more) at term and
      indications for labour induction. INTERVENTIONS: With their informed consent, 100
      eligible women were to be randomised to receive either sublingual misoprostol 50
      micrograms every 4 hours for up to five doses or oxytocin infusion after
      artificial rupture of membranes. Interim analysis was planned at a sample size of
      50. MAIN OUTCOME MEASURES: Vaginal delivery within 24 hours of induction.
      RESULTS: The study was terminated when interim analysis of the first 50 recruits
      showed that a significantly smaller proportion of misoprostol-treated women
      delivered vaginally within 24 hours of induction than in the conventional
      treatment group (68% vs 100%; relative risk, 0.68; 95% confidence interval, 0.51
      0.91; P=0.009), although comparable numbers of women eventually delivered
      vaginally. The mean induction to vaginal delivery interval was 4.5 hours longer
      in the misoprostol group (P=0.027). After misoprostol treatment, all women went
      into labour. Forty percent of them delivered without oxytocin. There was no
      significant difference in uterine hyperstimulation rate, operative delivery rate,
      and neonatal outcomes. Maternal satisfaction was higher in the misoprostol group
      (92% vs 60%; relative risk, 1.53; 95% confidence interval, 1.09-2.16; P=0.008).
      CONCLUSIONS: Despite being well accepted by women, labour induction using this
      regimen of sublingual misoprostol is less effective in achieving vaginal delivery
      within 24 hours.

PMID- 17028354
TI  - Hong Kong men with low incomes have worse health-related quality of life as
      judged by SF-36 scores.
AB  - OBJECTIVE: To analyse the association between income and health-related quality
      of life using the Medical Outcome Study Short Form 36 (SF-36) Chinese version in
      Hong Kong Chinese working population. DESIGN: Cross-sectional observation study.
      SETTING: A commercial company in Hong Kong. PARTICIPANTS: All clerical and
      administrative staff of a commercial company was invited to participate; 876 of
      the 1003 staff agreed. The subjects were categorised into three income groups
      according to monthly income in Hong Kong dollars (low, < or =10,000; middle,
      >10,000-25,000; high, >25,000). The mean age of the 288 men and 588 women was
      34.9 (standard deviation, 7.9; median, 34.0; range, 18-71) years. MAIN OUTCOME
      MEASURES: SF-36 scores on health-related quality of life. RESULTS: The
      distribution of income was 30% in high-, 54.8% in middle-, and 15.2% in low
      income groups. Women had similar SF-36 scores among different income groups. In
      men, for most variables there was a significant positive linear correlation
      between income and SF-36 scores. CONCLUSION: Low income is associated with a
      worse health-related quality of life in Hong Kong Chinese men.

PMID- 17028355
TI  - The short-to-midterm results of endovascular stent grafting for acute thoracic
      aortic diseases in Chinese patients.
AB  - OBJECTIVE: To review the results of endovascular treatment of acute thoracic
      aortic diseases in a group of Chinese patients. DESIGN: Retrospective study.
      SETTING: A tertiary referral hospital with a cardiothoracic surgery service.
      PATIENTS: All 15 patients presenting with acute thoracic aortic diseases between
      September 2001 and October 2005 inclusive, of whom eight had traumatic rupture,
      four had complicated acute dissections, two had mycotic aneurysms, and one an
      aneurysm with an aortobronchial fistula. INTERVENTIONS: Thoracic aortic stent
      grafting. MAIN OUTCOME MEASURES: Immediate success, 6-month and 1-year survival
      rates. RESULTS: The median follow-up period was 20.6 months (range, 0-50.1
      months). Stent grafts were deployed with immediate success in all patients. Two
      patients had ancillary bypass surgery for the supra-aortic branches. There were
      two in-hospital deaths. Four sustained access artery injury and needed graft
      repair. Computed tomography at 1 month showed complete thrombosis of the
      aneurysmal lumen or the thoracic aortic false lumen in 12 of 13 survivors.
      Computed tomography at 6 months showed complete thrombosis of the aneurysmal
      lumen or the false lumen in nine of 10 patients due for follow-up. Both 6-month
      and 1-year survival rates were 87%. CONCLUSIONS: Thoracic aortic stent grafting
      for acute thoracic aortic disease is feasible and has a high success rate, with
      good short-to-midterm results. However, the large size of the stent graft
      introducer set imposes a high risk of access artery injury, for which further
      improvements are necessary.

PMID- 17028356
TI  - Uterine fibroid embolisation in Chinese women: medium-term results.
AB  - OBJECTIVE: To evaluate the medium-term results of uterine fibroid embolisation in
      Chinese women with symptomatic uterine fibroids. DESIGN: Prospective case series
      study. SETTING: Gynaecology and Interventional Radiology units in a public
      hospital, Hong Kong. PATIENTS: Patients with symptomatic fibroids who underwent
      uterine fibroid embolisation in Queen Elizabeth Hospital from October 1998 to
      June 2004. RESULTS: Fifty women (mean age, 42.9 years; median follow-up period,
      27.5 months) were recruited. Most (82%) had menorrhagia as the chief presenting
      symptom. Embolisation was successful in 49 (98%) women. Complications occurred in
      12 (24%) patients, but were all self-limiting. Significant decrease in the median
      clinical uterine size (14 weeks vs 10 weeks) and median volume of the largest
      fibroid on magnetic resonance imaging (157.9 mL vs 45 mL) were observed during
      the first year. The reduction seemed to be maintained till the last follow-up.
      Menorrhagia improved in 34 (84%) patients, dysmenorrhoea in 28 (88%), pelvic pain
      in 18 (82%) and abdominal mass in 15 (83%). Poor response was found for urinary
      symptoms (29% improvement). Eight (16%) patients underwent hysterectomies after
      uterine fibroid embolisation. On logistic regression analysis, the only
      significant predictive factor for symptomatic improvement was fibroid volume
      reduction at 6 months (P=0.03). CONCLUSION: Uterine fibroid embolisation is an
      effective uterine-preserving therapy in patients with symptomatic fibroids;
      overall symptomatic improvement was estimated as 80%. Uterine or fibroid size
      reduction correlated well with clinical outcome. The impact of uterine fibroid
      embolisation on young women wishing to conceive is yet to be determined.

PMID- 17028357
TI  - Immuno-prophylaxis of babies borne to hepatitis B carrier mothers.
AB  - OBJECTIVES: To examine the efficacy of current hepatitis B immuno-prophylaxis and
      estimate the prevalence of S-mutant infections among local newborn babies.
      DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A
      total of 137 newborn babies delivered between the period of November 2000 and 30
      June 2001 inclusive, whose mothers were chronic hepatitis B surface antigen
      carriers. RESULTS: Of the 121 infants who were followed up for 12 months, three
      were found to be chronic hepatitis B virus carriers, giving a vertical
      transmission rate of 2.5%. One (0.8%) was suspected to be infected by the S
      mutant. All the three hepatitis B virus carrier babies were born to mothers with
      hepatitis B e antigen, but none to the eight mothers suspected to have S-mutants.
      Of 119 (98.3%) infants who developed hepatitis B surface antibody upon follow-up
      at 12 months, 35 were found to have hepatitis B e antigen at birth. All were born
      to hepatitis B e antigen-positive mothers. Only three of the 35 babies were found
      to be hepatitis B virus carriers. Most babies lost the hepatitis B e antigen by 6
      months of age; only the infected babies had the antigen persisting at 1 year of
      age. The non-infected infants' hepatitis B e antigen is likely transplacental.
      CONCLUSIONS: Our hepatitis B virus prophylaxis programme was effective at
      preventing perinatal infection and the non-infected infants' hepatitis B e
      antigen was likely transplacental.

PMID- 17028358
TI  - Recurrent pneumothorax in pregnancy: what should we do after placing an
      intercostal drain.
AB  - Recurrent pneumothorax is rare during pregnancy. We describe a Chinese woman,
      with a history of spontaneous pneumothorax managed with an intercostal drain, who
      developed a recurrent pneumothorax during her 32nd week of pregnancy. There is no
      consensus on management in this situation. We review the literature and discuss
      different management approaches. Thirty-six cases of antepartum pneumothorax have
      been reported in 31 case reports. An intercostal drain only (n=11) or surgeries
      (thoracotomy, n=9; or video-assisted thoracoscopy, n=2) were common treatment
      options with no surgical complications reported. Twenty-two (61%) patients
      progressed to a normal vaginal delivery, while the rest required forceps delivery
      (22%) or Caesarean section (14%). No single treatment option outweighed the
      others. There were no maternal or foetal complications reported in those who
      underwent antepartum surgical intervention. Surgical management of recurrent
      pneumothorax during pregnancy is well tolerated.

PMID- 17028359
TI  - Ex-utero intrapartum treatment: a controlled approach to the management of
      anticipated airway problems in the newborn.
AB  - Airway problems in an unborn foetus that may cause obstruction can be safely
      managed using an ex-utero intrapartum technique. Advanced technology now allows
      many congenital airway problems to be diagnosed in the prenatal period. Careful
      prenatal planning of an ex-utero intrapartum treatment allows safe airway control
      while the foetus remains on uteroplacental support. It avoids the need for
      emergent intervention of an acutely obstructed airway in a neonate that often has
      disastrous consequences.

PMID- 17028360
TI  - Autoimmune polyendocrinopathy type II in a Chinese patient.
AB  - Autoimmune polyendocrinopathy type II is rarely reported in Chinese patients. A
      42-year-old Chinese woman with a history of Hashimoto's thyroiditis and
      hypogonadotropic hypogonadism presented with pneumonia. During hospitalisation,
      she went into an adrenal crisis and diabetic ketoacidosis. Subsequent dynamic
      hormonal tests revealed primary and secondary adrenal insufficiency. She also had
      pernicious anaemia, possible alopecia areata, and myasthenia gravis. This
      constellation of multiple endocrine and non-endocrine disorders led to the
      diagnosis of autoimmune polyendocrinopathy type II. As the syndrome can be
      lethal, it is important to maintain a high index of suspicion, enabling early
      diagnosis and the appropriate replacement therapy, to ensure a successful
      outcome.

PMID- 17028361
TI  - A case of takotsubo cardiomyopathy: transient left ventricular apical ballooning.
AB  - A 78-year-old woman was admitted to hospital with central chest pain and the
      electrocardiographic and cardiac marker changes typical of acute anterior
      myocardial infarction. Coronary angiography revealed normal epicardial coronary
      arteries, and left ventriculography showed apical akinesis as well as basal
      hyperkinesis. This is a case of transient left ventricular apical ballooning or
      takotsubo cardiomyopathy, possibly attributable to catecholamine-mediated
      myocardial stunning.

PMID- 17028362
TI  - Typhoid osteomyelitis of the lumbar spine.
AB  - A 25-year-old Nepali man presented with a 20-day history of fever associated with
      a lower backache. Physical examination found tenderness over the lower lumbar
      vertebrae. Magnetic resonance imaging following intravenous contrast injection
      showed enhancement of the L4 and L5 vertebrae, particularly pronounced around the
      intervening disc, and areas of endplate erosion. Extra-vertebral enhancement and
      a small subligamentous anterior collection were also noted. Computed tomography
      guided needle aspiration was performed at the level of L4/5 disc material and
      culture of the specimen grew Salmonella typhi sensitive to ampicillin,
      ciprofloxacin, and ceftriaxone. The patient received intravenous ampicillin 2 g
      per 4 hours for 6 weeks. The back pain resolved completely and the patient was
      discharged. Typhoid osteomyelitis of the spine should be considered in the
      differential diagnosis in patients from endemic areas who present with fever and
      backache.

PMID- 17028363
TI  - Acute renal failure associated with prolonged intake of slimming pills containing
      anthraquinones.
AB  - Chinese herbal medicine preparations are widely available and often regarded by
      the public as natural and safe remedies for a variety of medical conditions.
      Nephropathy caused by Chinese herbs has previously been reported, usually
      involving the use of aristolochic acids. We report a 23-year-old woman who
      developed acute renal failure following prolonged use of a proprietary Chinese
      herbal slimming pill that contained anthraquinone derivatives, extracted from
      Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the
      concomitant intake of a non-steroidal anti-inflammatory drug, diclofenac. Renal
      pathology was that of hypocellular interstitial fibrosis. Spontaneous renal
      recovery occurred upon cessation of the slimming pills, but mild interstitial
      fibrosis and tubular atrophy was still evident histologically 4 months later.
      Although a causal relationship between the use of an anthraquinone-containing
      herbal agent and renal injury remains to be proven, phytotherapy-associated
      interstitial nephropathy should be considered in patients who present with
      unexplained renal failure.

PMID- 17028364
TI  - Unusual bleeding gastric ulcer.

PMID- 17028365
TI  - Health professionals and the International Code of Marketing of Breast-milk
      Substitutes.

PMID- 17028366
TI  - Who founded WHO?

PMID- 17028369
TI  - The genetics of autism spectrum disorders.
AB  - Epidemiological twin studies demonstrate that autism spectrum disorders (ASDs)
      represent genetic disorders. Subsequent analyses indicate that the causes of ASDs
      include less common single-gene mutations and chromosomal abnormalities, as well
      as ASDs caused by multiple interacting genes of weak effect. Genome-wide linkage
      analysis has identified several susceptibility loci for the ASDs, and positional
      and functional candidate genes have been identified that appear to represent
      susceptibility genes for the ASDs. Analysis of additional larger samples and the
      use of genome-wide association and high-throughput variant detection will lead to
      the identification of further genes for ASDs.

PMID- 17028368
TI  - Cerebral palsy.
AB  - Cerebral palsy (CP) is a group of disorders of movement and posture resulting
      from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of
      cases of CP in term infants originate in the prenatal period; in premature
      infants, both prenatal or postnatal causes contribute. The most prevalent
      pathological lesion seen in CP is periventricular white matter injury (PWMI)
      resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32
      wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a
      spectrum of cognitive and behavioral disorders. Oxidative stress and
      excitotoxicity resulting from excessive stimulation of ionotropic glutamate
      receptors on preOLs are the most prominent molecular mechanisms for PWMI.
      Asphyxia around the time of birth in term infants accounts for less than 15% of
      CP in developed countries but the incidence is higher in underdeveloped areas.
      Asphyxia causes a different pattern of brain injury and CP than is seen after
      preterm injuries. This type of CP is associated with the clinical syndrome of
      hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal
      ganglia, and brainstem are selectively vulnerable to injury. Experimental models
      indicate that neurons in the neonatal brain are more likely to die by delayed
      apoptosis extending over days to weeks than those in the adult brain. Neurons die
      by glutamate-mediated excitotoxicity involving downstream caspase-dependent and
      caspase-independent cell death pathways. Recent reports indicate that males and
      females preferentially utilize different pathways. Clinical trials indicate that
      mild hypothermia reduces death or disability in term infants following asphyxia
      and basic research suggests that this approach might be combined with
      pharmacological strategies in the future.

PMID- 17028371
TI  - The molecular pathology of Rett syndrome: synopsis and update.
AB  - Genetic mutations of the X-linked gene MECP2, encoding methyl-CpG-binding protein
      2, cause Rett syndrome (RTT) and other neurological disorders. It is increasingly
      recognized that MECP2 is a multifunctional protein, with at least four different
      functional domains: (1) a methyl-CpG-binding domain; (2) an arginine-glycine
      repeat RNA-binding domain; (3) a transcriptional repression domain; and (4) an
      RNA splicing factor binding region (WW group II binding domain). There is
      evidence that MECP2 is important for large-scale reorganization of
      pericentromeric heterochromatin during differentiation. Studies in MECP2
      deficient mouse brain have identified a diverse set of genes with altered levels
      of mRNA expression or splicing. It is still unclear how altered MECP2 function
      ultimately results in neuronal disease after a period of grossly normal
      development. However, mounting evidence suggests that neuronal health and
      development depend on precise regulation of MECP2 expression. In genetically
      engineered mice, both increased and decreased levels of MECP2 result in a
      neurological phenotype. Furthermore, it was recently discovered that MECP2 gene
      duplications underlie a small number of atypical Rett cases and mental
      retardation syndromes. The finding that MECP2 levels are tightly regulated in
      neurons has important implications for the design of gene replacement or
      reactivation strategies for treatment of RTT, because affected individuals
      typically are somatic mosaics with one set of cells expressing a mutated MECP2
      from the affected X, and another set expressing normal MECP2 from the unaffected
      X. Further studies are necessary to elucidate the molecular pathology of both
      loss-of-function and gain-of-function mutations in MECP2.

PMID- 17028370
TI  - Attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based
      on the presence of developmentally inappropriate levels of impulsivity,
      overactivity, and inattentiveness. It is a familial condition with a complex
      pattern of inheritance. Variation of several genes involved in the regulation of
      dopamine, norepinephrine, and serotonin neurotransmission is associated with
      ADHD. We highlight the two most prominent findings with the dopamine D4 receptor
      (DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for
      the understanding of the cellular and neurobiological basis for ADHD. Cognitive
      and functional studies using electrophysiology and brain imaging frequently
      indicate altered processing in ADHD during performance on cognitive tasks
      hypothesized to measure a "core" deficit, such as response inhibition. Yet,
      children with ADHD appear to suffer from a more general deficit, including
      impairment in attentional alerting, orienting, response preparation, and control.
      Reward processes are also altered and, further, a strong association emerges with
      intraindividual variability, with several causal hypotheses being proposed. Task
      performance correlates with underactivation of, especially, frontostriatal areas
      of the brain, but an extended network of brain regions is also implicated.
      Electroencephalography studies indicate abnormalities in ADHD in relation to slow
      wave activity, linked to underarousal. These advances in the areas of genetics,
      cognitive function, neurophysiology, and neuroanatomy of ADHD give important
      leads for interdisciplinary research that aims to delineate the causal pathways.
      Such research is only at its beginning, but is illustrated by recent findings of
      an association between DAT1 and increased response variability in ADHD.

PMID- 17028372
TI  - Ataxia-telangiectasia and related diseases.
AB  - Appropriate cellular signaling responses to DNA damage and the ability to repair
      DNA are fundamental processes that are required for organismal survival. Ataxia
      telangiectasia (A-T) is a rare neurodegenerative disease that results from
      defective DNA damage signaling. Understanding the molecular basis of A-T has
      provided many critical insights into the cellular response to DNA double-strand
      breaks (DSBs). A-T is a syndrome that shows pronounced neurodegeneration of the
      nervous system coincident with immune deficiency, radiosensitivity, and cancer
      proneness. A-T results from inactivation of the A-T mutated (ATM) kinase, a
      critical protein kinase that regulates the response to DNA-DSBs by selective
      phosphorylation of a variety of substrates. Therefore, understanding the ATM
      signaling program has important biological ramifications for nervous system
      homeostasis. Underscoring the importance of the DNA-DSBs response in the nervous
      system are other diseases related to A-T that also result from defects in this
      signaling pathway. In particular, defects in the DNA damage sensor, the Mre11
      RAD50-NBS1 complex, also lead to syndromes with neurological deficits and
      overlapping phenotypes to A-T. Collectively, these diseases highlight the
      critical importance of appropriate responses to DNA-DSBs to maintain homeostasis
      in the nervous system.

PMID- 17028373
TI  - Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in
      newborns.
AB  - Kernicterus is a devastating, chronic disabling neurological disorder whose
      central nervous system (CNS) sequelae reflect both a predilection of bilirubin
      toxicity for neurons (rather than glial cells) and the regional topography of
      bilirubin-induced neuronal injury that is characterized by prominent basal
      ganglia, cochlear, and oculomotor nuclei involvement. The molecular pathogenesis
      of bilirubin-induced neuronal cell injury, although incompletely understood,
      likely reflects the untoward effects of hazardous unconjugated bilirubin
      concentrations on plasma, mitochondrial, and/or endoplasmic reticulum (ER)
      membranes. These membrane perturbations, in turn, might lead to the genesis of
      neuronal excitotoxicity, mitochondrial energy failure, or increased intracellular
      calcium concentration [Ca2+]i. These three phenomena are likely to be linked
      spatially and temporally in the pathogenesis of bilirubin-induced neuronal
      injury. Downstream events triggered by increased [Ca2+]i may include, among
      others, the activation of proteolytic enzymes, apoptotic pathways, and/or
      necrosis, the individual occurrence of which is likely a function of the degree
      and duration of bilirubin exposure. A recent study demonstrates the activation of
      mitogen-activated protein kinase signal transduction pathways by bilirubin
      heralding a degree of complexity regarding the molecular mechanism(s) of
      bilirubin-induced neurotoxicity not previously appreciated. There remains,
      however, a paucity of data regarding specific effects of bilirubin on
      intracellular signaling and cell death pathways, particularly in vivo. An
      enhanced understanding of the molecular pathogenesis of bilirubin-induced
      neuronal injury will lead to the identification of potential novel interventional
      strategies to protect the CNS against kernicterus.

PMID- 17028374
TI  - The neurobiology of the tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a multisystem disorder that affects numerous
      organ systems. Brain lesions that form during development, known as tubers, are
      highly associated with epilepsy, cognitive disability, and autism. Following the
      identification of two genes and their encoded proteins, TSC1 (hamartin) and TSC2
      (tuberin), responsible for TSC, identification of several downstream protein
      cascades that might be affected in TSC have been discovered. Of primary
      importance is the mammalian target of rapamycin pathway that controls cell growth
      and protein synthesis. The mechanisms governing brain lesion growth have not been
      fully identified but likely altered regulation of the mammalian target of
      rapamycin cascade by hamartin and tuberin during development leads to aberrant
      cell growth. Secondary effects of TSC gene mutations might disrupt normal
      neuronal migration and cerebral cortical lamination. Numerous studies have
      identified changes in gene and protein expression in animal models of TSC and in
      human TSC brain specimens that contribute to altered brain cytoarchitecture. This
      review will provide an overview of the neurobiological aspects of TSC.

PMID- 17028376
TI  - Low Serum Selenium Is Associated with Anemia Among Older Women Living in the
      Community: the Women's Health and Aging Studies I and II.
AB  - Anemia is common among older adults, and a substantial proportion of anemia in
      the older population is of indeterminate cause. Low selenium levels have been
      associated with anemia in animals, but this relationship has not been well
      characterized in humans. The objective was to determine whether low serum
      selenium concentrations are associated with anemia among older women. We
      conducted a cross-sectional analysis of participants in the Women's Health and
      Aging Studies, a population-based sample of women living in the community in
      Baltimore, MD, USA. Of 632 women, aged 70-79 yr, 14.1% of women were anemic
      (hemoglobin <120 g/L). The prevalence of anemia among women in the lowest to
      highest quartile of serum selenium was 22.4%, 14.6%, 11.9% and 6.6%, respectively
      (p < 0.0001). An increase in loge selenium was associated with a reduced risk of
      anemia (odds ratio per 1 SD increase = 0.63, 95% confidence interval = 0.47
      0.84), adjusting for age, education, chronic diseases, iron status, and serum
      interleukin-6. We conclude that low serum selenium is independently associated
      with anemia among older women living in the community.

PMID- 17028377
TI  - Effect of zinc supplementation on serum leptin levels and insulin resistance of
      obese women.
AB  - Leptin is thought to be a lipostatic signal that contributes to body weight
      regulation. Zinc might play an important role in appetite regulation and its
      administration stimulates leptin production. However, there are few reports in
      the literature on its role on leptin levels in the obese population. The present
      work assesses the effect of zinc supplementation on serum leptin levels in
      insulin resistance (IR). A prospective double-blind, randomized, clinical,
      placebo-controlled study was conducted. Fifty-six normal glucose-tolerant obese
      women (age: 25-45 yr, body mass index [BMI] = 36.2 +/- 2.3 kg/m2) were randomized
      for treatment with 30 mg zinc daily for 4 wk. Baseline values of both groups were
      similar for age, BMI, caloric intake, insulin concentration, insulin resistance,
      and zinc concentration in diet, plasma, urine, and erythrocytes. Insulin and
      leptin were measured by radioimmunoassay and IR was estimated by the homeostasis
      model assessment (HOMA). The determinations of zinc in plasma, erythrocytes, and
      24- h urine were performed by using atomic absorption spectrophotometry. After 4
      wk, BMI, fasting glucose, and zinc concentration in plasma and erythrocyte did
      not change in either group, although zinc concentration in the urine increased
      from 385.9 +/- 259.3 to 470.2 +/- 241.2 +/- microg/24 h in the group with zinc
      supplementation (p < 0.05). Insulin did not change in the placebo group, whereas
      there was a significant decrease of this hormone in the supplemented group. HOMA
      also decreased from 5.8 +/- 2.6 to 4.3 +/- 1.7 (p < 0.05) in the zinc
      supplemented group but did not change in the placebo group. Leptin did not change
      in the placebo group. In the zinc group, leptin was 23.6 +/- 12.3 microg/L and
      did not change. More human data from a unique population of obese individuals
      with documented insulin resistance would be useful in guiding future studies on
      zinc supplementation (with higher doses or longer intervals) or different
      measures.

PMID- 17028378
TI  - Dose-related influence of sodium selenite on apoptosis in human thyroid follicles
      in vitro induced by iodine, EGF, TGF-beta, and H2O2.
AB  - Apoptosis of thyroid follicular cells is induced by high doses of iodide,
      epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as
      well as H2O2 and might be attenuated by antioxidants. Therefore, we examined the
      apoptotic index induced by these substances in selenium-treated vs untreated
      human thyroid follicular cells. Reconstituted human thyroid follicles were
      incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none.
      The follicles were then distributed to 24-well plates and incubated with
      potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-beta (5 ng/mL), or H2O2
      (100 muM). Apoptosis was determined by a mitochondrial potential assay and the
      number of apoptotic cells counted by two independent, experienced technicians and
      the glutathione peroxidase (GPx) activity was determined. Asignificant increase
      of apoptic cells was obtained in control thyroid follicles treated with iodine
      (5, 10, or 20 microM), thyroidstimulating hormone (TSH) 1, or 10 mU/mL in
      combination with 5 and 10 microM iodine, EGF (5 ng/mL) and TGF-beta (5 ng/mL), or
      H2O2 (100 microM) (p < 0.001). In contrast, in thyroid follicles preincubated
      with 10 or 100 nM sodium selenite, the apoptototic index was identical to the
      basal rate. In H2O2-treated follicles, the apoptotic index was still
      significantly elevated but 50% lower compared to control cells. The GPx activity
      increased from 1.4 +/- 0.2 to 2.25 +/- 0.4 mU/microg DNA with 10 nMselenite and
      2.6 + 0.4 mU/microg DNA with 100 nM selenite. Sodium selenite might increase the
      antioxidative potential in human thyroid follicles in vitro and therefore
      diminish the apoptosis induced by TGF-beta, EGF, iodide, and even H2O2.

PMID- 17028375
TI  - Lissencephaly 1 linking to multiple diseases: mental retardation,
      neurodegeneration, schizophrenia, male sterility, and more.
AB  - Lissencephaly 1 (LIS1) was the first gene implicated in the pathogenesis of type
      1 lissencephaly. More than a decade of research by multiple laboratories has
      revealed that LIS1 is a key node protein, which participates in several pathways,
      including association with the molecular motor cytoplasmic dynein, the reelin
      signaling pathway, and the platelet-activating factor pathway. Mutations in LIS1
      interacting proteins, either in human, or in mouse models has suggested that LIS1
      might play a role in the pathogenesis of numerous diseases such as male
      sterility, schizophrenia, neuronal degeneration, and viral infections.

PMID- 17028379
TI  - Blood alpha-Tocopherol, selenium, and glutathione peroxidase changes and adipose
      tissue fatty acid changes in kittens with experimental steatitis (yellow fat
      disease): a comparative study between the domestic shorthaired and Siamese breed.
AB  - Twenty domestic shorthaired (DSH) and 20 Siamese (S) kittens were allocated into
      4 breed-specific groups, of 10 kittens each, that were fed exclusively cooked
      sardines (F groups) or commercial feline canned food based on oily fish (C
      groups) for a 4-month period. Clinical signs were scored every 15 d along with
      body weight recording and blood sampling for the measurement of alpha-tocopherol
      and selenium (Se) concentrations and glutathione peroxidase (GSH-Px) activity.
      Subcutaneous adipose tissue samples were obtained per month to determine its
      fatty acid composition. Steatitis, reproduced in all 20 F-group kittens, was
      accompanied by systemic signs in 5 DSH and 6 S animals. The severity of the
      disease reached its zenith at the second week in the DSH-F-group kittens and the
      fourth and sixth week in the S-F-group kittens. alpha-Tocopherol plasma level was
      significantly lower in F groups compared to their corresponding controls, whereas
      the opposite was true for Se and red blood cell GSH-Px activity. In conclusion,
      the results of this study have shown that although the morbidity rate is not
      different between the two breeds, the delay of Siamese cats to develop
      symptomatic steatitis is presumably attributed to an inherent resistance as a
      result of the long-standing evolution of more efficient antioxidant mechanisms.
      Also, the changes in fatty acid composition of the adipose tissue lipids are
      associated with the progression of the age, breed, and diet and probably with the
      inflammatory changes of the adipose tissue.

PMID- 17028380
TI  - Effect of dietary zinc on the levels and distribution of Fatty acids and vitamin
      A in blood plasma chylomicrons.
AB  - The aim of this work was to explore the effects of a low- and high-zinc diet and
      vitamin Aon the distribution of fatty acids in chylomicrons. Mongolian Gerbils
      were fed a basal diet (for 3 wk) containing 8 or 38 mg zinc/kg of feed (low-zinc
      group [termed LZ group] and saturated zinc group [termed SZ group],
      respectively). The following day, the animals were given sunflower oil containing
      50 nmol vitamin A. The results showed that the concentration of zinc in blood
      plasma was similar in both groups. The amount of plasma chylomicrons was lower in
      the LZ group than in the SZ group (p < 0.001). The concentration of retinol in
      blood plasma was lower in the LZ group than in the SZ group (p < 0.01). However,
      the results demonstrated an increase in the blood plasma retinol concentration in
      the LZ group compared to the SZ group when calculated per milligram of plasma
      chylomicrons (p < 0.01). In plasma chylomicrons, fatty acids corresponding to
      16:0, 16:1, 17:0, 17:1, 18:0, 18:1, 18:2, 18:3, 20:0, 21:0, and 20:4 were
      detected. The fatty acid distribution was similar in both groups. There was no
      major difference in the concentration of fatty acids in plasma chylomicrons
      between both experimental groups, except for 20:4 (a lower amount was found in
      the SZ group). Our results show that dietary zinc influences both the amount of
      chylomicrons in blood plasma and the concentrations of retinol and arachidonic
      acid in chylomicrons.

PMID- 17028381
TI  - Correlation between ZIP2 messenger RNA expression and zinc level in rat lateral
      prostate.
AB  - Zinc content in rat lateral prostate (LP) is higher compared with the other
      tissues, but the zinc retention system in the prostate remains unclear. In the
      present study, we examined the expression of ZRT, a IRT-like protein (ZIP) family
      transporter in rat prostate. The zinc level in rat LP was higher compared with
      the ventral (VP) and dorsal prostate (DP). The predicted ZIP2 mRNA was really
      expressed in LP at a high level. The expression was decreased in LP from
      castrated rats, associated with a decrease in zinc level, and these changes were
      prevented by testosterone replacement. Moreover, ZIP2 expression levels in LP
      positively correlated with the zinc levels. These findings strongly suggest that
      ZIP2 is involved in zinc homeostasis of rat prostate.

PMID- 17028382
TI  - Influence of sodium fluoride and caffeine on the concentration of fluoride ions,
      glucose, and urea in blood serum and activity of protein metabolism enzymes in
      rat liver.
AB  - The aim of the study was examining the effect of fluoride ions and caffeine
      administration on glucose and urea concentration in blood serum and the activity
      of protein metabolism enzymes and selected enzymes of the urea cycle in rat
      liver. The study was carried out using 18 male Sprague-Daowley rats (4.5 mo old).
      Rats were divided into three groups. Group I received distilled water ad libitum.
      Group II received 4.9 mg F-/kg body mass/d of sodium fluoride in the water, and
      group III received sodium fluoride (in the above-mentioned dose) and 3 mg/kg body
      mass/d of caffeine in the water. After 50 d, the rats were anesthetized with
      thiopental and fluoride ions, glucose, and urea concentration in blood serum were
      determined. Also determined were the activities of aspartate aminotransferase,
      alanine aminotransferase glutamate dehydrogenase, ornithine carbamoylotransferase
      and arginase in liver homogenates. Liver was taken for pathomorphological
      examinations. The applied doses of F- (4.9 mg/kg body mass/d) and F- + caffeine
      (4.9 mg F-/kg body mass/d + 3 mg caffeine/kg body mass/d) resulted in a
      statistically significant increase of fluoride ion concentration in blood serum,
      a slight increase of the glucose concentration, and no changes in the
      concentration of urea in blood serum. This might testify to the absence of kidney
      lesions for the applied concentrations of F-. No change in the functioning of
      hepatocytes was observed; however, slight disturbances have been noted in the
      functioning of the liver, connected with the activation of urea cycle, increase
      of arginase activity, and accumulation of F- in this organ. There was no observed
      significant influence of caffeine supplementation on the obtained results.

PMID- 17028383
TI  - Influence of silicon on cobalt, zinc, and magnesium in baker's yeast,
      Saccharomyces cerevisiae.
AB  - Silicon (Si, as silicate) is involved in numerous important structure and
      function roles in a wide range of organisms, including man. Silicate availability
      influences metal concentrations within various cell and tissue types, but, as
      yet, clear mechanisms for such an influence have been discovered only within the
      diatoms and sponges. In this study, the influence of silicate on the
      intracellular accumulation of metals was investigated in baker's yeast
      (Saccharomyces cerevisiae). It was found that at concentrations up to 10 mM,
      silicate did not influence the growth rate of S. cerevisiae within a standard
      complete medium. However, an 11% growth inhibition was observed when silicate was
      present at 100 mM. Intracellular metal concentrations were investigated in yeast
      cultures grown without added silicate (-Si) or with the addition of 10 mM
      silicate (+Si). Decreased amounts of Co (52%), Mn (35%), and Fe (20%) were found
      within +Sigrown yeast cultures as compared to -Si-grown ones, whereas increased
      amounts of Mo (56%) and Mg (38%) were found. The amounts of Zn and K were
      apparently unaffected by the presence of silicon. +Si enhanced the yeast growth
      rate for low-Zn2+ medium, but it decreased the growth rate under conditions of a
      low Mg2+ medium and did not alter the growth rates in high Zn2+ and Co2+ media.
      +Si doubled the uptake rate of Co2+ but did not influence that of Zn2+. We
      propose that a possible explanation for these results is that polysilicate
      formation at the cell wall changes the cell wall binding capacity for metal ions.
      The toxicity of silicate was compared to germanium (Ge, as GeO2), a member of the
      same group of elements as Si (group 14). Hence, Si and Ge are chemically similar,
      but silicate starts to polymerize to oligomers above 5 mM, whereas Ge salts
      remain as monomers at such concentrations. Ge proved to be far more toxic to
      yeast than Si and no influence of Si on Ge toxicity was found. We propose that
      these results relate to differences in cellular uptake.

PMID- 17028389
TI  - [Familial subtelomeric abnormality der(4)t(4p16.3;21q22.3) as a cause of mental
      retardation and mild dysmorphic features].
AB  - A 3-year-old girl with developmental delay, dysmorphic features, hypotonia and
      microcephaly is presented. Fluorescence in situ hybridization (FISH) with
      subtelomeric probes (Multiprobe Chromoprobe T System) revealed monosomy and
      trisomy of subtelomeric regions 4p and 21q respectively. Clinical and pedigree
      data were analyzed and the phenotype -genotype correlation for partial monosomy
      4p and trisomy 21q identified in the proband is also presented.

PMID- 17028390
TI  - [Characterization of marker chromosomes using molecular cytogenetic methods in
      patients with mental retardation and congenital malformations].
AB  - INTRODUCTION: Until recently, great variety of marker chromosomes and
      difficulties with their identification have presented a problem for cytogenetic
      and clinical interpretation of the karyotype. At present, molecular cytogenetic
      methods of chromosome analysis enable precise characterization of such
      abnormalities providing knowledge necessary for estimation of their genetic risk.
      AIM: The aim of the study was molecular cytogenetic characterization of marker
      chromosomes recognized in three patients, an analysis of clinical features in
      relation to the abnormality and estimation of genetic risk of identified markers.
      PATIENTS AND METHODS: Karyotypes of three phenotypically abnormal patients were
      estimated in lymphocytes from peripheral blood by G banding analysis. Marker
      chromosomes were identified by fluorescence in situ hybridization (FISH),
      multiplex FISH, multicolor band and high resolution comparative genomic
      hybridization methods. RESULTS: Marker chromosomes were identified as inv
      dup(22)(pter->q11.2::q11.2->pter), der(8)(:p22->q11.2:), der(2l)(:pter->q21.3:)
      and der(19)(:p11->q13.1). All of them contained euchromatic sequences. First
      marker, an inverted duplication of chromosome 22q11.2 corresponding to tetrasomy
      of this chromosome region was recognized in a child with partial cat eye
      syndrome. Two further markers derived from chromosomes 8 and 21 were found in a
      child with mosaic karyotype and clinical features of trisomy 8p. In the third
      case additional chromosome material was derived from chromosome 19 and it was
      found in a patient with mild mental retardation and clinical features of ovary
      dysgenesis. Genetic risk of identified marker chromosomes except for mar(19) was
      estimated as high. CONCLUSIONS: Our results provide further evidence for
      diagnostic value of molecular cytogenetic methods. They also confirmed the
      general opinion of the high risk of phenotypic abnormalities in the carriers of
      marker chromosomes containing euchromatic sequences.

PMID- 17028391
TI  - [Cytogenetic-molecular analysis of balanced chromosomal rearrangements in nine
      patients with intellectual disability, dysmorphic features and congenital
      abnormalities].
AB  - INTRODUCTION: In about 6% of individuals with intellectual disability, dysmorphic
      features and congenital anomalies, an abnormal, apparently balanced karyotype is
      found. These abnormalities may result from abnormal expression of genes at the
      breakpoints, presence of a submicroscopic deletion, or other unbalanced
      chromosome aberrations. In such cases, the detailed analysis of breakpoints of
      balanced chromosome rearrangements may help with identification of genes
      responsible for patient's clinical features. AIM OF WORK: Was the explanation of
      causes of abnormal phenotype in the carriers with abnormal but balanced
      karyotype. MATERIAL AND METHODS: Cytogenetic-molecular analysis performed in nine
      patients with mental retardation, dysmorphic features and congenital anomalies.
      Studies with subtelomeric probes, high resolution comparative genomic
      hybridization (HR-CGH) and fluorescence in situ hybridization (FISH) with region
      specific BAC clones were performed. RESULTS: Seventeen chromosome breakpoint
      regions were narrowed to 200-400 kb. In one case, an 0.5-Mb submicroscopic
      deletion associated with more complex rearrangement has been found. Mapping of
      the breakpoints and information obtained from the UCSC Human Genome Browser data
      base enabled identification of 46 genes in these regions. Twelve genes, that may
      have been disrupted as a result of the patients' chromosomal rearrangement, were
      found. At four different breakpoints the identified genes (NRCAM, NPTX1, NMT1,
      MAPT, HDAC5 and MEF2C) may be due to a position effect. CONCLUSIONS: The results
      confirm earlier suggestions concerning reasons of abnormal phenotype in the
      patients with balanced chromosome rearrangements and present the value of
      detailed analysis of the genome in such cases.

PMID- 17028392
TI  - [On the way to gene therapy in cystic fibrosis].
AB  - Cystic fibrosis (CF) is the most common recessively inherited lethal disease
      among the Caucasian population. CF is caused by mutations in the CFTR gene.
      Although several organs and tracts are affected, severe lung disease is the cause
      of the most of the morbidity and mortality in CF individuals. Current treatment
      is aimed at slowing the inevitable progression of lung disease, rather than
      halting it, or preventing its onset. The isolation of the gene responsible for CF
      suggested the feasibility of new therapeutic possibilities based on the CFTR gene
      transfer to CF patients. At present, somatic CF gene therapy clinical trials,
      using mostly animals but also CF patients, are being conducted. Gene therapy
      development is restricted by the lack of the appropriate gene vector systems,
      which could be successfully used to transfer in vivo and protect the therapeutic
      gene. This is because of the many extracellular, intracellular and immunological
      barriers, which protect living organisms against invasion of foreign genetic
      material. Future improvement in gene therapy depends on the more effective ways
      of the gene transfer methods, creation animal models of the human diseases and
      development of strategies involved in the new gene construct formulation, which
      facilitate to control gene transcription activity.

PMID- 17028393
TI  - [Genetic markers in the pathogenesis of osteopenia and osteoporosis in cystic
      fibrosis].
AB  - Cystic fibrosis (CF) is the most common recessive autosomal disorder in the
      Caucasian population. Advancements in treatment of CF patients have increased
      life expectancy from approximately 2 to over 30 years. Complex approach to the
      health status and management of CF children increased the interest in
      osteoarticular system pathology in these patients. This particularly concerns
      osteopenia and osteoporosis. Multiple studies indicate that osteoporosis is a
      genetic disease in which the phenotype is determined by both environmental and
      genetic factors and by mutual interactions between them. It is postulated that
      osteoporosis occurs as the result of mutations and/or polymorphisms in many
      different genes. The evidence for the genotype-phenotype correlation came from
      the analysis of mutations and polymorphisms in Collagen Type I Alpha 1 (COL1A1),
      Vitamin D Receptor (VDR) and Calcitonin receptor (CALCR) genes. Determination of
      osteoporotic genetic background may lead to better understanding of the
      pathomechanism of osteoporosis in CF patients and to help further define
      treatment guidelines.

PMID- 17028394
TI  - [Clinical symptoms and molecular pathogenesis of Noonan syndrome--current
      concepts].
AB  - Noonan syndrome (NS; MIM 163950) is an autosomal dominant disorder. With
      incidence of 1/1000 to 1/2500 live births, NS belongs to the most common genetic
      disorders. Typical features of NS are: short stature, chest deformities,
      congenital heart defects, cryptorchidism and dysmorphic features. Mutations of
      PTPN11 gene (located on chromosome 12q24.1) are responsible for NS and are
      identified in 33-60% cases. Less than half of the cases are familial. This paper
      presents current opinion on clinical symptoms, molecular pathogenesis and
      possibilities of growth hormone therapy. The genotype--phenotype correlation is
      also discussed.

PMID- 17028395
TI  - [Primary torsion dystonia--clinical and molecular aspects].
AB  - Dystonias are a heterogeneous group of neurological disorders. In this paper we
      present clinical and molecular characteristics of inherited primary torsion
      dystonias. Clinical data and current concepts on the pathogenesis of dystonias
      with known molecular defect are presented in detail. Therapeutic options in
      patients with primary dystonias are also discussed.

PMID- 17028396
TI  - [Identification of immunoglobulin and T-cell receptor gene rearrangements-
      prerequisite for monitoring of minimal residual disease in Polish acute
      lymphoblastic leukemia patients based on European standards. Preliminary
      results].
AB  - OBJECTIVE: Initiation and popularization of routine molecular diagnostics of
      minimal residual disease (MRD) are currently one of the most urgent challenges in
      Polish hemato-oncology. The paper is aimed to present preliminary results of
      identification of immunoglobulin (Ig) and T-cell receptor (TCR) gene
      rearrangements and quantitative assessment of MRD levels in Polish children with
      acute lymphoblastic leukemia (ALL). The results are presented in the context of
      clinical significance of MRD study, current methodology of MRD assessment and
      standardization process in Western Europe. MATERIAL: DNA isolated from bone
      marrow / bone marrow mononuclear cells obtained at diagnosis from 26 children (25
      B-precursor ALL, 1 T-ALL) aged 1.3-16.5 years. METHODS: PCR-heteroduplex
      analysis, based on standard BIOMED-1 and BIOMED-2 primer combinations and
      protocols for detection of rearrangements and clonality assessment; sequencing of
      clonal PCR products and comparison with germline sequences of Ig/TCR genes for
      identification of the rearranged genes andjunctional regions; real-time
      quantitative PCR (RQ-PCR) with the use of TaqMan probes for assessment of follow
      up MRD levels (in 11 patients). RESULTS: Clonal TCRG, incomplete TCRD, Vdelta2
      Jalpha, TCRB, IGK-Kde and IGH gene rearrangements were detected in 61, 61, 35,
      13, 39 and 83% of patients, respectively, which was generally concordant with
      published data for patients of other European nations. CONCLUSIONS: There is an
      urgent need to broaden the scope of minimal residual disease study in Poland and
      to develop Polish standards of MRD diagnostics, based on current European
      experience and standards.

PMID- 17028397
TI  - [Pathogenic mutation or polymorphism? (How to find criteria)].
AB  - The classification of amino-acid substitutions into pathogenic mutations and
      harmless polymorphisms should be revised. In the recent years it was shown that
      some amino-acid substitutions considered as pathogenic mutations were
      polymorphisms. Similarly, some 'harmless' polymorphisms have been shown to be
      pathogenic mutations. Functional analysis considered as a good method to estimate
      the pathogenic nature of mutations is also limited. The selection of DNA samples
      for the control group is also difficult. Due to the molecular mechanism mediated
      by recently discovered exonic splicing enhancers and silencers (ESE and ESS) it
      is hard to predict a pathogenic effect of some mutations. In addition, the
      phenotype variability observed between unrelated patients harboring the same
      mutation may reflect the effects of modifying genes as well as the lack of
      association between mutation and "its" phenotype. The aim of this study is to
      describe the problem of the pathogenic effect of mutations.

PMID- 17028398
TI  - [Attention deficit hyperactivity disorder (ADHD)--molecular and genetic aspects].
AB  - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder of childhood, affecting approximately 5-10% of children. ADHD is
      considered to be a multifactorial disorder because both genetic and environmental
      components may contribute to its progress. The etiology of attention deficit
      hyperactivity disorder (ADHD) is unknown, however family, twin and adoption
      studies have suggested that genetic factors are very important in its
      etiopathogenesis. The research of genetic basis of ADHD consists of linkage
      analysis, candidate gene approach and association studies. These analyses and
      also investigations on animal models of disease suggest that mutations in genes
      involved in dopaminergic, serotonergic and adrenergic systems are likely to be
      responsible for ADHD.

PMID- 17028399
TI  - [Hutchinson-Gilford progeria in the light of contemporary genetics].
AB  - Hutchinson-Gilford progeria causing premature aging of children is a genetic
      disease and according to most authors has an autosomal dominant inheritance. It
      has been regarded as a model of the process of aging. In 2003 mutations in the
      LMNA gene, localized f in chromosome 1, responsible for the disease, were
      identified. The most frequent mutation is located in exon 11, C1824T and does not
      change glycin in position 608 of protein chain, but activates cryptic splice
      site. This results in shortened lamin A synthesis which is named progerin. Point
      mutations in other exons of LMNA, found in progeria patients, are responsible for
      atypical phenotypes.

PMID- 17028400
TI  - [Carrier detection in Duchenne/Becker muscular dystrophy in the families in which
      the DNA of the affected person is not available].
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe, progressive, X
      linked muscular disease, which affects 1 in 3500 male newborns. The course of the
      other allelic form of the disease (Becker muscular dystrophy--BMD) is milder.
      Female relatives of affected subjects may carry the mutated gene. AIM OF THE
      STUDY: The purpose of this study was to detect the carrier among 23 families
      affected with DMD/BMD, in whom DNA from the deceased affected person was not
      available. MATERIAL AND METHODS: The analysis of polymorphic sequences within the
      dystrophin gene was applied. RESULTS: Informative results were obtained in 26 of
      39 females examined (66%): 7 females were found to be carriers and 19
      noncarriers. In one family the deletion could be detected in the mother and
      sister of the deceased proband.

PMID- 17028401
TI  - An adaptive input-output modeling approach for predicting the glycemia of
      critically ill patients.
AB  - In this paper we apply system identification techniques in order to build a model
      suitable for the prediction of glycemia levels of critically ill patients
      admitted to the intensive care unit. These patients typically show increased
      glycemia levels, and it has been shown that glycemia control by means of insulin
      therapy significantly reduces morbidity and mortality. Based on a real-life
      dataset from 15 critically ill patients, an initial input-output model is
      estimated which captures the insulin effect on glycemia under different settings.
      To incorporate patient-specific features, an adaptive modeling strategy is also
      proposed in which the model is re-estimated at each time step (i.e., every hour).
      Both one-hour-ahead predictions and four-hours-ahead simulations are executed.
      The optimized adaptive modeling technique outperforms the general initial model.
      To avoid data selection bias, 500 permutations, in which the patients are
      randomly selected, are considered. The results are satisfactory both in terms of
      forecasting ability and in the clinical interpretation of the estimated
      coefficients.

PMID- 17028402
TI  - Pseudo-polar drive patterns for brain electrical impedance tomography.
AB  - Brain electrical impedance tomography (EIT) is a difficult task as brain tissues
      are enclosed by the skull of high resistance and cerebrospinal fluid (CSF) of low
      resistance, which makes internal resistivity information more difficult to
      extract. In order to seek a single source drive pattern that is more suitable for
      brain EIT, we built a more realistic experimental setting that simulates a head
      with the resistivity of the scalp, skull, CSF and brain, and compared the
      performance of adjacent, cross, polar and pseudo-polar drive patterns in terms of
      the boundary voltage dynamic range, independent measurement number, total
      boundary voltage changes and anti-noise performance based on it. The results
      demonstrate that the pseudo-polar drive pattern is optimal in all the aspects
      except for the dynamic range. The polar and cross drive patterns come next, and
      the adjacent drive pattern is the worst. Therefore, the pseudo-polar drive
      pattern should be chosen for brain EIT.

PMID- 17028403
TI  - Investigation of fall-risk using a wearable device with accelerometers and rate
      gyroscopes.
AB  - A clinical tool and an associated test that can assess fall-risk in elderly
      patients have been designed. The clinical tool was based on a wearable device
      with accelerometers and rate gyroscopes to identify trunk kinematic parameters.
      The test was based on a posturography protocol with different constraints and
      statistical analysis of the kinematic parameters. Statistical clustering based on
      the Mahalanobis distance was carried out using three groups of 30 subjects (1,
      age < 65 years; 2, age > or = 65 years and 3, age > or = 65 years and a fall
      history). The method was statistically validated using three groups of 100
      subjects. The test allowed discrimination of elderly subjects with a high fall
      risk with high specificity > or = 0.930 and sensitivity > or = 0.939.

PMID- 17028404
TI  - Analysis of electroencephalograms in Alzheimer's disease patients with multiscale
      entropy.
AB  - The aim of this study was to analyse the electroencephalogram (EEG) background
      activity of Alzheimer's disease (AD) patients using multiscale entropy (MSE). MSE
      is a recently developed method that quantifies the regularity of a signal on
      different time scales. These time scales are inspected by means of several coarse
      grained sequences formed from the analysed signals. We recorded the EEGs from 19
      scalp electrodes in 11 AD patients and 11 age-matched controls and estimated the
      MSE profile for each epoch of the EEG recordings. The shape of the MSE profiles
      reveals the EEG complexity, and it suggests that the EEG contains information in
      deeper scales than the smallest one. Moreover, the results showed that the EEG
      background activity is less complex in AD patients than control subjects. We
      found significant differences between both subject groups at electrodes F3, F7,
      Fp1, Fp2, T5, T6, P3, P4, O1 and O2 (p-value < 0.01, Student's t-test). These
      findings indicate that the EEG complexity analysis performed on deeper time
      scales by MSE may be a useful tool in order to increase our knowledge of AD.

PMID- 17028405
TI  - Wound measurement by curvature maps: a feasibility study.
AB  - A non-contact wound measurement method by laser scanner and curvature maps is
      presented. A patient's foot ulcer is scanned by FastSCAN ten times over a three
      week period. With the surface's 3D coordinates, curvature maps of the ulcerous
      area are calculated. Utilizing a specified rim curvature value, the wound edge is
      detected and processed via cubic spline smoothing, which is qualitatively
      verified by a photograph. Subsequently, the depth, area and volume of the wound
      can be calculated. The results indicate that laser scanning followed by curvature
      analysis might be a potential clinical tool for non-contact measurement of
      wounds.

PMID- 17028406
TI  - Simulation of Brugada syndrome using cellular and three-dimensional whole-heart
      modeling approaches.
AB  - Brugada syndrome (BS) is a genetic disease identified by an abnormal
      electrocardiogram (ECG) (mainly abnormal ECGs associated with right bundle branch
      block and ST-elevation in right precordial leads). BS can lead to increased risk
      of sudden cardiac death. Experimental studies on human ventricular myocardium
      with BS have been limited due to difficulties in obtaining data. Thus, the use of
      computer simulation is an important alternative. Most previous BS simulations
      were based on animal heart cell models. However, due to species differences, the
      use of human heart cell models, especially a model with three-dimensional whole
      heart anatomical structure, is needed. In this study, we developed a model of the
      human ventricular action potential (AP) based on refining the ten Tusscher et al
      (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573-89) model to incorporate
      newly available experimental data of some major ionic currents of human
      ventricular myocytes. These modified channels include the L-type calcium current
      (I(CaL)), fast sodium current (I(Na)), transient outward potassium current
      (I(to)), rapidly and slowly delayed rectifier potassium currents (I(Kr) and
      I(Ks)) and inward rectifier potassium current (I(Ki)). Transmural heterogeneity
      of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by
      varying the maximum conductance of I(Ks) and I(to). The modified AP models were
      then used to simulate the effects of BS on cellular AP and body surface
      potentials using a three-dimensional dynamic heart-torso model. Our main findings
      are as follows. (1) BS has little effect on the AP of endocardial or mid
      myocardial cells, but has a large impact on the AP of epicardial cells. (2) A
      likely region of BS with abnormal cell AP is near the right ventricular outflow
      track, and the resulting ST-segment elevation is located in the median precordium
      area. These simulation results are consistent with experimental findings reported
      in the literature. The model can reproduce a variety of electrophysiological
      behaviors and provides a good basis for understanding the genesis of abnormal ECG
      under the condition of BS disease.

PMID- 17028407
TI  - Quantification of the timing of continuous modulated muscle activity in a
      repetitive-movement task.
AB  - The timing of muscle activity is commonly measured in studies of motor control.
      In repetitive-movement tasks, muscle activity may be continuous, and no defined
      onset or offset of activity may be measured. This does not imply that no timing
      of muscle activity occurs. Where activity is continuous, this timing will
      typically be exhibited by modulation of the amplitude of the signal in specific
      movement phases. The existence of this electromyographic (EMG) timing is
      dependent upon the existence of EMG amplitude modulation. This paper investigates
      this relationship in developing a quantification algorithm of EMG timing in a
      repetitive-movement task. A frequency domain quantification algorithm involving
      EMG linear-envelope generation is used. An EMG simulation algorithm is used to
      test this algorithm and determine the minimal amplitude-modulation threshold for
      timing detection. At five repetitive-movement speeds (25, 50, 75, 100 and 125
      cycles of movement per minute), thresholds between 1.558 and 2.326 times maximal
      to minimal linear-envelope amplitude are required for reliability of timing
      detection. Analysis of variance indicates that the robustness of the
      quantification algorithm was not significantly affected by burst width (F = 3.69,
      p = 0.055) or the underling input timing parameter (F = 0.52, p = 0.992). The
      phase-lead/lag quantification algorithm represents a useful tool for the analysis
      motor control via EMG during repetitive-movement tasks.

PMID- 17028408
TI  - Electrical impedance tomography in extremely prematurely born infants and during
      high frequency oscillatory ventilation analyzed in the frequency domain.
AB  - Functional electrical impedance tomography (EIT) measures relative impedance
      change that occurs in the chest during a distinct observation period and an EIT
      image describing regional relative impedance change is generated. Analysis of
      such an EIT image may be erroneous because it is based on an impedance signal
      that has several components. Most of the change in relative impedance in the
      chest is caused by air movement but other physiological events such as cardiac
      activity change in end expiratory level or pressure swings originating from a
      ventilator circuit can influence the impedance signal. We obtained EIT images and
      signals in spontaneously breathing healthy adults, in extremely prematurely born
      infants on continuous positive airway pressure and in ventilated sheep on
      conventional mechanical or high frequency oscillatory ventilation (HFOV). Data
      were analyzed in the frequency domain and results presented after band pass
      filtering within the frequency range of the physiological event of interest. Band
      pass filtering of EIT data is necessary in premature infants and on HFOV to
      differentiate and eliminate relative impedance changes caused by physiological
      events other than the one of interest.

PMID- 17028409
TI  - Evaluation of renal functional parameters in different settings of isolated organ
      hemoperfusions.
AB  - Isolated porcine kidneys are commonly used to study physiological and
      pathophysiological aspects of renal homeostasis but standardized evaluation
      procedures of renal function in this model do not exist so far. A double
      logarithmical nomogram is established for filtration and reabsorption functions
      in isolated and hemoperfused porcine kidneys using different perfusion settings.
      Model validity was demonstrated by the levels of urine flow and sodium excretion
      showing expected alteration levels of lowering in the ADH-group and increasing in
      the furosemide-group of isolated kidneys. Creatinine-clearance values were in
      constant ranges within each specific perfusion group as indicated by the nomogram
      procedure. The present studies used a nomogram method to analyze the effects of
      different renal perfusion settings in a porcine model of kidney perfusion. The
      method may be of use to differentiate various kidney perfusion parameters both at
      the experimental and clinical levels.

PMID- 17028410
TI  - Reference values for whole body and cerebral multi-frequency bio-impedance data
      in neonates less than 12 h postpartum.
AB  - Multiple frequency bio-electrical impedance analysis (MFBIA) may be useful for
      monitoring fluid balance in newborn infants or to provide early prediction of the
      outcome following perinatal asphyxia. A reference range of data is needed for
      identification of babies with abnormal impedance values. This was a cross
      sectional observational study in 84 term and near-term healthy neonates less than
      12 h postpartum. Whole body and cerebral MFBIA measurements were performed at the
      bedside in the post-natal ward. Gestational age, post-natal age, gender,
      birthweight, head circumference and foot length measures were recorded. Reference
      values for impedance at the characteristic frequency (Z(C)) and resistance at
      zero frequency (R(0)) are reported for whole body and cerebral impedance.
      Significant correlations (p < 0.05) were observed between whole body impedance
      and birthweight, footlength and head circumference. Females had a significantly
      higher whole body R(0) than males. Cerebral impedance did not correlate
      significantly with any of the demographic measures and there were no gender
      differences observed for cerebral impedance. The reference range for whole body
      multi-frequency bio-impedance values in term and near-term infants within the
      first 12 h postpartum can be calculated from the footlength (FL) using the
      following equations: Z(C) = (942.9 - 4.818*FL) +/- 124.6 Omega; R(0) = (1042 -
      4.520*FL) +/- 135.5 Omega. For cerebral impedance the reference range is 29.5
      48.7 Omega for Z(C) and 33.7-58.0 Omega for R(0).

PMID- 17028411
TI  - Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human
      skin in vivo.
AB  - Trace gases emitted by human skin in vivo are monitored non-invasively and in
      real time using laser-based photoacoustic detection and proton-transfer reaction
      mass spectrometry. A small quartz cuvette is placed on the skin to create a
      headspace from which a carrier gas transports the skin emissions to the detection
      systems. The transparency of quartz to ultraviolet radiation (UVR) allows
      investigation of UVR-related trace gas emissions. As a demonstration of this
      measurement system, the effect of supplemental intake of systemic antioxidants on
      UVR-induced lipid peroxidation is investigated. The production by the skin of
      three biomarkers of UVR-induced lipid peroxidation (ethylene, acetaldehyde and
      propanal) is monitored. Although no significant effect of antioxidant intake was
      observed, the method presented here is a novel and promising technique for
      investigation of human skin in vivo.

PMID- 17028412
TI  - Effect of body surface area calculations on body fat estimates in non-obese and
      obese subjects.
AB  - The purpose of the present study was to compare body surface area (BSA) estimates
      using two equations (Dubois and Dubois versus Livingston) and their respective
      effects on per cent body fat (%BF) obtained with two molecular approaches of body
      composition analysis, two-compartment (2C) and five-compartment (5C) models. Body
      composition data using the 2C model were studied in healthy adults, 432 women
      (body mass index (BMI): 28.3 +/- 4.4 kg m(-2)) and 147 men (BMI: 26.8 +/- 3.9 kg
      m(-2)), while another sample of 126 women (BMI: 30.4 +/- 3.7 kg m(-2)) was
      evaluated using the 5C model. Measures of body volume (BV) assessed by air
      displacement plethysmography, bone mineral content by dual energy x-ray
      absorptiometry (DXA) and total-body water by deuterium dilution were used to
      estimate %BF with the 5C model. Comparison of means and linear regression
      analysis was performed. Using BSA(Dubois), either in 2C and 5C models, BV and %BF
      estimates were significantly underestimated compared to results obtained using
      BSA(Livingston) (p < 0.05). BMI was strongly associated with %BF differences
      using BSA(Dubois) and BSA(Livingston) in both 2C (men: r = 0.90; women: r = 0.88)
      and 5C models (r = 0.88). Though %BF(Dubois) and %BF(Livingston) were strongly
      associated (r(2) = 1.000), some variability was observed on %BF differences using
      BSA(Dubois) and BSA(Livingston). These findings suggest that BSA calculation is
      critical in BF estimation, supporting the use of a more accurate equation for non
      obese and obese subjects.

PMID- 17028413
TI  - Analysis of the QT interval and its variability in healthy adults during rest and
      exercise.
AB  - The aim of the present study was to quantify the variability of
      electrocardiographic QT and RR intervals during rest and dynamic physical
      exercise, and to interpret these variabilities in terms of relative autonomic
      modulation of the atrial and ventricular myocardium. We also sought to
      characterize the relationships between QT, heart rate-corrected QT (QT(c)) and RR
      intervals, and to consider their associations with differential autonomic
      regulation. Nine males and eight females of similar age (22.8 +/- 4.7 years),
      mass (75.5 +/- 13.0 kg) and aerobic fitness (43.6 +/- 7.7 ml kg(-1) min(-1))
      (mean +/- SD) undertook progressive bicycle exercise. A three-lead Holter ECG was
      recorded continuously during pre-exercise, exercise and recovery, and mean values
      of RR, QT, QT(c), QT variability index (QTVI) and mean-normalized QT variance
      (QTVN) were determined. At the onset of exercise QTVI increased rapidly compared
      with rest and remained significantly elevated throughout exercise and recovery.
      There were significant differences between QT(a)VI and QT(e)VI (QT measured from
      Q wave onset to T wave apex (QT(a)) and T wave end (QT(e)), respectively)
      throughout the experimental protocol. QTVI was significantly reduced in males
      compared with females prior to exercise but was similar thereafter. We suggest
      that physical exercise perturbs the resting QT-RR relationship owing to the onset
      of differential parasympathetic modulation of the atrial and ventricular
      myocardium. QTVI can be used to quantify the relative autonomic influence on the
      atrial and ventricular myocardium during rest and exercise, and might be related
      to HR-dependent and HR-independent influences on the QT interval.

PMID- 17028414
TI  - Ballistocardiogram artifact removal from EEG signals using adaptive filtering of
      EOG signals.
AB  - We estimated ballistocardiogram (BCG) components in EEG signals recorded inside
      an MRI magnet using the electro-oculogram (EOG) signals recorded simultaneously
      with the EEG signals. Since the EOG signals are measured near the EEG measuring
      points, it is thought that the BCG components in the EOG signals resemble the BCG
      components in the EEG signals. To estimate the BCG components in the EEG signals,
      we applied the Kalman filter to the EOG and EEG signals recorded inside a 3.0 T
      MRI magnet. After removing the estimated BCG components from the EEG signals, we
      extracted the visual-evoked potentials (VEPs) from the BCG-removed EEG signals.
      To validate the efficacy of Kalman filtering in the BCG artifact removal, we have
      compared three types of VEPs of eight healthy subjects: one extracted from the
      raw EEG signals measured outside the magnet and the others extracted from the BCG
      removed EEG signals measured inside the magnet. The BCG artifacts have been
      removed with Kalman filtering as well as with the conventional BCG template
      subtraction method for the sake of comparison. No significant difference in
      waveforms, latencies and amplitudes has been found between the two types of VEPs
      extracted from the two kinds of BCG-removed EEG signals.

PMID- 17028415
TI  - Detrended fluctuation analysis of laser Doppler flowmetry time series: the effect
      of extrinsic and intrinsic factors on the fractal scaling of microvascular blood
      flow.
AB  - The relative contribution of extrinsic (central) and intrinsic (local)
      oscillatory mechanisms to the fractal scaling of blood flow in forearm cutaneous
      microcirculation is unclear. The aim of this study was to investigate the
      contributions of these mechanisms to the fractal properties of the blood flow
      signal by using their frequency spectrum in the analyses. To evoke local
      oscillatory components, acetylcholine (ACh) was iontophoresed into the forearm
      and cutaneous perfusion was measured by a laser Doppler flowmeter (LDF) at rest.
      Depending on the involved factors in ACh-induced vasodilatation, central, cardiac
      and respiratory, signals have also increasingly appeared in LDF. The detrended
      fluctuation analysis (DFA) of filtered LDF time series demonstrated that the LDF
      was fractal with three distinct scaling regions. Furthermore, the findings of the
      present study indicated that these regions are related to the frequency bands of
      well-known control systems of blood flow and were called cardiac, cardio
      respiratory and local regions. The mean scaling exponent increased with
      vasodilatation in the cardiac region but decreased and even changed its sign in
      the cardio-respiratory region. Inhibition of a local vasodilator mechanism not
      only decreased the scaling exponent of the local region but also eliminated the
      effect of respiratory coupling on fractal scaling. These findings suggest that
      the scaling exponents might have a diagnostic value for detecting pathological
      dynamics in vascular beds.

PMID- 17028416
TI  - Isolation and characterization of rat pituitary endothelial cells.
AB  - Most previous studies that determined the effect of estradiol on angiogenesis
      used endothelial cells from nonpituitary sources. Because pituitary tumor tissue
      receives its blood supply via portal and arterial circulation, it is important to
      use pituitary-derived endothelial cells in studying pituitary angiogenesis. We
      have developed a magnetic separation technique to isolate endothelial cells from
      pituitary tissues and have characterized these cells in primary cultures.
      Endothelial cells of the pituitary showed the existence of endothelial cell
      marker, CD31, and of von Willebrand factor protein. These cells in cultures also
      showed immunoreactivity of estrogen receptors alpha and beta. The angiogenic
      factors, vascular endothelial growth factor and basic fibroblast growth factor,
      significantly increased proliferation and migration of the pituitary-derived
      endothelial cells in primary cultures. These results suggest that a magnetic
      separation technique can be used for enrichment of pituitary-derived endothelial
      cells for determination of cellular mechanisms governing the vascularization in
      the pituitary.

PMID- 17028417
TI  - Friedrich Feyrter: a precise intellect in a diffuse system.
AB  - Prior to the contributions of Friedrich Feyrter (1895-1973), the regulation of
      gastrointestinal function was an ill-understood field that was polarized by a
      combination of the inability of clinical scientists to perceive the relationship
      between the cellular elements of 'nervism' and the newly recognized chemical
      messenger system. Feyrter, an Austrian pathologist of luminescent intellect and
      possessed of rigorous analytic capacity, recognized the interface of the
      divergent elements (neural and endocrine) and established the concept of the
      diffuse neuroendocrine system. His pathological descriptions of the specialized
      neuroendocrine cells producing biologically active substances and regulating
      homeostasis by a network functioning via endocrine, paracrine, and neuracrine
      mechanisms laid the basis for contemporary understanding of gut function. In
      1938, Feyrter identified Helle Zellen (clear cells) of the pancreas and
      gastrointestinal tract, which was later incorporated into the amine precursor
      uptake decarboxylation concept of endocrine cells by A.G.E. Pearse (1916-2003).
      Feyrter proposed a diffuse network as a functional regulatory system as opposed
      to the then current doctrine of 'organ' regulation in his 1938 manuscript Uber
      diffuse endokrine epitheliale Organe. In addition to this seminal contribution,
      the prodigious intellect of Feyrter produced an array of novel observations
      including benign and malignant tumors of the skin, gastrointestinal tract, and
      eyes, carcinoid tumors and the carcinoid syndrome, the genesis of the nevus, the
      transformation of lipids and disorders of cellular metabolism. Sadly, the
      contributions of Feyrter were obscured in the catastrophe of wartime Germany and
      his accomplishments little recognized. We describe the life and times of this
      gifted scientist, teacher, and pathologist, often referred to as the 'Father of
      Neuroendocrinology'.

PMID- 17028418
TI  - Progestin concentrations are increased following paced mating in midbrain,
      hippocampus, diencephalon, and cortex of rats in behavioral estrus, but only in
      midbrain of diestrous rats.
AB  - BACKGROUND: The progesterone (P(4)) metabolite, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP), acts in the midbrain ventral tegmental area (VTA) to
      modulate the intensity and duration of lordosis. 3alpha,5alpha-THP can also have
      anti-anxiety and anti-stress effects in part through actions in the hippocampus.
      Separate reports indicate that manipulating 3alpha,5alpha-THP levels in the VTA
      or hippocampus respectively can influence lordosis and affective behavior.
      3alpha,5alpha-THP levels can also be altered by behavioral experiences, such as
      mating or swim stress. Whether endogenous levels of 3alpha,5alpha-THP modulate
      and/or are increased in response to affective and/or reproductively-relevant
      behaviors was investigated. METHODS: In Experiment 1, rats in behavioral estrus
      or diestrus were individually tested sequentially in the open field, elevated
      plus maze, partner preference, social interaction, and paced mating tasks and
      levels of 17beta-estradiol (E(2)), P(4), dihydroprogesterone (DHP), and
      3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex were
      examined. In Experiments 2 and 3, rats in behavioral estrus or diestrus, were
      individually tested in the battery indicated above, with, or without, paced
      mating and tissues were collected immediately after testing for later assessment
      of endocrine measures. RESULTS: In Experiment 1, behavioral estrous, compared to
      diestrous, rats demonstrated more exploratory, anti-anxiety, social, and
      reproductive behaviors, and had higher levels of E(2) and progestins in serum,
      midbrain, hippocampus, diencephalon, and cortex. In Experiment 2, in midbrain and
      hippocampus, levels of 3alpha,5alpha-THP and its precursor DHP were increased
      among rats in behavioral estrus that were mated. In diencephalon, and cortex, DHP
      levels were increased by mating. In Experiment 3, in midbrain, levels of
      3alpha,5alpha-THP and its precursor DHP were increased among diestrous rats that
      were tested in the behavioral battery with mating as compared to those tested in
      the behavioral battery without mating. CONCLUSIONS: Increased levels of
      3alpha,5alpha-THP in behavioral estrus versus diestrous rats are associated with
      enhanced exploratory, anti-anxiety, social, and reproductive behaviors. Rats in
      behavioral estrus that are mated have further increases in 3alpha,5alpha-THP
      and/or DHP levels in midbrain, hippocampus, diencephalon, and cortex than do non
      mated rats in behavioral estrus, whereas diestrous rats only show 3alpha,5alpha
      THP increases in midbrain in response to behavioral testing that included mating.

PMID- 17028419
TI  - Prednisone blunts airway neutrophilic inflammatory response due to ozone exposure
      in asthmatic subjects.
AB  - BACKGROUND: The effect of corticosteroids on the ozone (O3)-induced airway
      inflammation is still debated. OBJECTIVE: The aim of the study was to confirm the
      effect of a short-term treatment with oral glucocorticosteroids on O3-induced
      airway inflammation, detected by induced sputum analysis, and on functional
      response in glucocorticosteroid-naive subjects. METHODS: A randomized, placebo
      controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out.
      Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27
      ppm O3 and to air in random order, after 4 days of treatment with prednisone (25
      mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary
      function test was measured; 6 h afterexposure, sputum induction was done.
      RESULTS: Oral glucorticosteroids did not prevent pulmonary function decrement due
      to O3. After placebo, the percentage of neutrophils in induced sputum was
      significantly higher after O3 than after air [52.1 (15.7-77.3) vs. 17.8 (1.7
      58.4), p=0.02, O3 vs. air]. This difference was lost after 4 days of treatment
      with prednisone [35.2% (10-96.2) vs. 30.9% (6.1-75.6), n.s., O3 vs. air].
      Neutrophil elastase in sputum supernatant increased after O3 exposure in the
      sample obtained after placebo, but not after prednisone treatment. CONCLUSIONS:
      This study confirms that glucocorticosteroids reduce inflammatory airway
      response, but do not prevent the airway functional impairment after O3 exposure.

PMID- 17028420
TI  - Autologous serum skin test for autoantibodies is associated with airway
      hyperresponsiveness in patients with asthma.
AB  - BACKGROUND: Autoimmune diseases have been implicated as a cause of intrinsic
      asthma; however, there is little data on the role of autoimmunity in the
      pathogenesis of asthma. OBJECTIVE: The purpose of this study was to investigate
      circulating functional autoantibodies against the high-affinity IgE receptor
      FcepsilonRI or IgE in patients with asthma. METHODS: Twenty-eight patients with
      asthma and 19 control subjects were included. All subjects were skin tested with
      autologous serum to assess for the potential presence of receptor FcepsilonRI or
      IgE autoantibodies. If the serum-induced wheal diameter was 1.5 mm larger than
      the histamine-induced wheal diameter and that was 3 mm larger than the saline
      induced wheal diameter at 30 min, the reaction was defined positive. RESULTS: Of
      the 47 total subjects (both asthma patients and control subjects), 13 (27.7%) had
      a positive autologous serum skin test (ASST). Of the 28 asthma patients, 8
      (28.6%) were regarded as having autoimmune origin. Autoantibodies against
      FcepsilonRI or IgE were found in asthma patients, irrespective of atopic status
      (atopy+ 3/13 vs. atopy- 5/15). The wheal diameter related to ASST was not related
      to atopy. Asthma patients with ASST-positive results as compared with patients
      with ASST-negative results exhibited a significant increased airway
      hyperresponsiveness (PC(20) methacholine, 2.70 +/- 1.27 vs. 9.08 +/- 2.35; p <
      0.026). CONCLUSION: Our data demonstrate that aberrant autoantibodies against the
      high-affinity IgE receptor FcepsilonRI or IgE are related to airway
      hyperresponsiveness in patients with asthma.

PMID- 17028421
TI  - Glucocorticoid regulation of GLT-1 glutamate transporter isoform expression in
      the rat hippocampus.
AB  - BACKGROUND: In the rat hippocampus, the predominate glutamate transporters are
      GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress
      increases GLT-1b expression throughout the hippocampus while more selectively
      increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b
      expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1
      expression is regulated by stress-induced increases in extracellular glutamate
      levels in the CA3 region. METHODS: In order to differentiate between the actions
      of GCs and glutamate, we examined GLT-1 isoform expression in adrenalectomized
      (ADX) rats and rats exposed to stress levels of GCs. RESULTS: ADX rats revealed
      no significant differences in GLT-1b mRNA or protein levels compared to sham
      operated controls or ADX rats given GC replacement. However, rats exposed to
      stress levels of GCs exhibited increases in GLT-1b protein expression in the CA3
      region and the dentate gyrus. GLT-1 mRNA expression was increased by ADX,
      increases that were inhibited by GC replacement. Similarly, stress levels of GCs
      increased GLT-1 protein expression throughout the hippocampus. CONCLUSIONS: Taken
      together, these data indicate that GLT-1b protein expression is regulated by
      stress levels of GCs while the regulation of GLT-1 mRNA and protein expression
      provides another example of the biphasic actions of GCs in the central nervous
      system.

PMID- 17028422
TI  - Effect of G-force on bicuspid aortic valve in aviators.
AB  - BACKGROUND AND AIMS: Bicuspid aortic valve (BAV) is a common congenital cardiac
      malformation. The major complications are aortic stenosis (AS), aortic
      regurgitation (AR), infectious endocarditis and aortic dissection. This paper
      aims to assess the hemodynamic importance of incidentally-found BAV in military
      aviators and evaluate the effect of high G-force on disease progression. METHODS:
      Aviators with BAV were detected by reviewing all cardiac assessment records
      between 1987 and 2005. All aviators underwent annual flight surgeon examination.
      Echocardiography was performed as recommended by our cardiologists and flight
      surgeons. RESULTS: Eight newly diagnosed cases of BAV were found. All of the
      aviators continued active aviation throughout the study period. Repeat
      echocardiography demonstrated progressive widening of the aortic diameter in five
      of the eight aviators. No worsening of valve dysfunction was seen in those with
      mild aortic regurgitation at diagnosis. Left ventricular dimensions and function
      did not deteriorate. No new valve complications, including infectious
      endocarditis, were seen. The age at diagnosis strongly correlated with the root
      diameter change; both total (r = 0.74, p = 0.02) and annualized (r = 0.78, p =
      0.02) change. Over a mean follow-up period of 12.1 years, no difference was seen
      in the progression of BAV in high-performance as compared to low-performance
      aviators. CONCLUSIONS: Exposure to G-force and anti-G maneuvers does not appear
      to worsen cardiac and valve function in aviators with BAV.

PMID- 17028423
TI  - Inhibition of restenosis development after mechanical injury: a new field of
      application for malononitrilamides?
AB  - OBJECTIVE: To investigate the efficacy of the malononitrilamide FK778 to prevent
      vascular smooth muscle cell (SMC) migration/proliferation, and vascular fibrosis,
      the key events in restenosis development using in vivo and in vitro studies.
      BACKGROUND: Since the high rate of restenosis after percutaneous transluminal
      coronary angioplasty limited its long-term success, the implementation of locally
      delivered antiproliferative/immunosuppressive agents became advantageous.
      METHODS: Rats underwent balloon denudation of the abdominal aorta and received
      sirolimus, tacrolimus, or FK778 for 28 days in varying doses. Aortas were
      harvested for histologic evaluation, profibrotic gene expression, and organ
      chamber studies. Antifibrotic, antiproliferative and antimigratory effects of the
      immunosuppressants were further evaluated in vitro. RESULTS: Histology of
      untreated animals revealed marked intimal hyperplasia with moderate luminal
      obliteration. Neointima formation was dose-dependently attenuated by all three
      agents with FK778 and sirolimus being most efficacious. Organ chamber relaxation
      studies showed a leftward shift of the nitroglycerin and the acetylcholine dose
      responses in all treatment groups, indicating diminished endothelial dysfunction.
      In vivo, only FK778 treatment revealed a significant downregulation of the TGF
      beta/vasorin system which could be explained by upregulation of the TGF-beta
      inhibitory mediator SMAD7. In vitro, FK778 showed most potent antiproliferative
      and antimigratory effects on SMC compared with sirolimus and tacrolimus. Only the
      antiproliferative effect of FK778 was due to pyrimidine synthesis blockade and
      could be reversed by uridine supplementation. CONCLUSIONS: The malononitrilamide
      FK778 proved highly efficacious against restenosis development by targeting two
      major components of intimal hyperplasia: SMC proliferation/migration and vascular
      fibrosis. Thus, the introduction of malononitrilamide-loaded stents may be a
      promising effort for future strategies.

PMID- 17028424
TI  - Time relation between a syncopal event and documentation of atrioventricular
      block in patients with bifascicular block: clinical implications.
AB  - BACKGROUND: Transient high-degree atrioventricular (AV) block is a common cause
      of syncope in patients with bifascicular block (BFB) but the intermittent nature
      of AV block makes ECG documentation a challenge. A sensitive and safe tool to
      investigate BFB patients with syncope would be a bradycardia-detecting pacemaker,
      which provides a possibility of studying the time relation between the index
      syncopal episode and the development of high-degree AV block. METHODS: Twenty
      seven patients with BFB and syncope were studied prospectively. All patients
      received a single-chamber ventricular-based pacemaker with bradycardia-detecting
      ability. A bradycardia episode was defined as a heart rate of < 30 beats/min
      lasting > or = 6 s. RESULTS: During a median follow-up of 60 months, a
      bradycardia event was detected in 14 patients (52%), of whom 13 also had
      documented high-degree AV block on ECG. The median time between the syncopal
      episode and the first pacemaker-detected bradycardia event was 5 months and after
      an additional median time of 6 months, high-degree AV block was documented on the
      ECG. In 10 of 13 patients (77%) high-degree AV block was documented within 24
      months of the syncopal episode corresponding to an annual incidence of 19% during
      the first 2 years of follow-up in the study population. CONCLUSION: In this group
      of BFB patients a syncopal episode was highly predictive of the development of
      high-degree AV block within 24 months, justifying pacemaker therapy without prior
      ECG verification.

PMID- 17028425
TI  - Myelin-associated oligodendrocytic basic protein: a family of abundant CNS myelin
      proteins in search of a function.
AB  - The myelin-associated oligodendrocytic basic protein (MOBP) family constitutes
      the third most abundant protein in CNS myelin. The mouse Mobp gene comprises
      eight exons. Mobp pre-mRNA processing gives rise to at least seven Mobp splice
      variants which are expressed solely in the oligodendrocyte. The predicted
      proteins all, with one exception, share a 68 residue amino terminus, encoded by
      exon 3. The carboxyl termini differ in length, giving rise to the diverse array
      of the protein isoforms. Like myelin basic protein, MOBP is present in the major
      dense line of CNS myelin suggesting a role in the compaction or stabilization of
      myelin. However, Mobp homozygous null mice display no overt clinical phenotype
      and no defect in the process of myelination. MOBP can induce experimental
      allergic encephalomyelitis in mice and has been proposed to have a role in the
      pathogenesis of multiple sclerosis. Despite 10 years of rigorous study, the
      normal physiological function of MOBP remains unknown.

PMID- 17028426
TI  - Activation, proliferation and commitment of endogenous stem/progenitor cells to
      the oligodendrocyte lineage by TS1 in a rat model of dysmyelination.
AB  - Wild-type and myelin-deficient rats received a single intraparenchymal injection
      of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus
      callosum at postnatal day 4. The fate of endogenous stem cells in the brain was
      examined by the expression of the stem cell marker nestin, together with Tf,
      neurofilaments and glial fibrillary acidic protein from 2 to 14 days after
      injection. Treated mutants lacked nestin expression in the ventricular wall and
      had an increase in nestin-labeled radial cell processes in the subventricular
      regions, and extended into the parenchyma. The subventricular zone was populated
      by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells
      originated by proliferation and were identified as OLs based upon Tf expression.
      Thus, TS1 is an effective treatment to promote endogenous subventricular zone
      progenitor proliferation, migration and OL lineage specification. This strategy
      offers for the first time the possibility of myelin restoration to treat myelin
      disorders.

PMID- 17028427
TI  - Inhibition of PC-PLC blocked the survival of mouse neural cells by up-regulating
      the expression of integrin beta4 and Rb.
AB  - In order to understand the survival signals of neural cells during the
      development of the central nervous system (CNS), we explored the role of
      phosphatidylcholine-specific phospholipase C (PC-PLC) in the survival of primary
      culture mouse neural cells (MNCs). We found that when the activity of PC-PLC in
      the neural cells was suppressed by its specific inhibitor, D609 (tricyclodecan-9
      yl-xanthogenate), the cell survival was blocked, the viability of the cells
      remarkably declined. At the same time, the expressions of integrin beta4 and Rb
      protein were evidently elevated. We also examined the intracellular ROS (reactive
      oxygen species) levels after the cells were treated with D609. The result showed
      that the ROS level in neural cells was reduced. Our data suggested that PC-PLC
      had an important role in regulating neural cell survival, and PC-PLC might
      perform its function by upregulating the expressions of integrin beta4 and Rb
      protein. The changes of intracellular ROS level induced by D609 indicated that a
      modest level of ROS might be indispensable to neural cell survival.

PMID- 17028428
TI  - The role of dopamine receptors in the neurobehavioral syndrome provoked by
      activation of L-type calcium channels in rodents.
AB  - In rodents, activation of L-type calcium channels with +/-BayK 8644 causes an
      unusual behavioral syndrome that includes dystonia and self-biting. Prior studies
      have linked both of these behaviors to dysfunction of dopaminergic transmission
      in the striatum. The current studies were designed to further elucidate the
      relationship between +/-BayK 8644 and dopaminergic transmission in the expression
      of the behavioral syndrome. The drug does not appear to release presynaptic
      dopamine stores, since microdialysis of the striatum revealed dopamine release
      was unaltered by +/-BayK 8644. In addition, the behaviors were preserved or even
      exaggerated in mice or rats with virtually complete dopamine depletion. On the
      other hand, pretreatment of mice with D(3) or D(1/5) dopamine receptor
      antagonists attenuated the behavioral effects of +/-BayK 8644, while pretreatment
      with D(2) or D(4) antagonists had no effect. In D(3) receptor knockout mice, +/
      BayK 8644 elicited both dystonia and self-biting, but these behaviors were less
      severe than in matched controls. In D(1) receptor knockout mice, behavioral
      responses to +/-BayK 8644 appeared exaggerated. These results argue that the
      behavioral effects of +/-BayK 8644 are not mediated by a presynaptic influence.
      Instead, the behaviors appear to result from a postsynaptic activation of the
      drug, which does not require but can be modified by D(3) or D(1/5) receptors.

PMID- 17028429
TI  - Characterization of mouse striatal precursor cell lines expressing functional
      dopamine receptors.
AB  - Dopamine and its receptors appear in the developing brain early in the embryonic
      period and dopamine receptor activation influences proliferation and
      differentiation of neuroepithelial precursor cells. Since dopamine D(1) and D(2)
      receptor activation produces opposing effects on precursor cell activity,
      dopamine's overall effects may correlate with relative numbers and activity of
      each receptor subtype on the precursor cells. Dopamine receptor expression and
      activity in individual precursor cells in the intact brain are difficult to
      ascertain. Therefore, cell lines with known receptor expression profiles can be
      useful tools to study dopamine's influence on neuroepithelial cells. We report
      characterization of dopamine receptor expression and activity profiles in three
      mouse striatal precursor cell lines and suggest that these cell lines can be
      valuable tools to study dopamine's effects on striatal precursor cell
      proliferation and differentiation.

PMID- 17028430
TI  - Differentiated dopaminergic MN9D cells only partially recapitulate the
      electrophysiological properties of midbrain dopaminergic neurons.
AB  - The cell line MN9D, a fusion of embryonic ventral mesencephalic and neuroblastoma
      cells, is extensively used as a model of dopamine (DA) neurons because it
      expresses tyrosine hydroxylase and synthesizes and releases DA. These cells are
      also used to test mechanisms and potential therapeutics relevant to the loss of
      DA neurons in Parkinson's disease. To date, little work has been done to
      determine whether MN9D cells electrophysiologically resemble mature DA neurons.
      We examined sodium, calcium and potassium currents in undifferentiated and
      differentiated MN9D cells, and compared these to those found in acutely
      dissociated mouse substantia nigra pars compacta DA neurons. It was observed that
      undifferentiated MN9D cells bore no resemblance to DA neurons. Upon
      differentiation with butyric acid with or without a prior treatment with glial
      cell line-derived neurotrophic factor, differentiated MN9D cells produce an
      electrophysiological profile that more closely resembles substantia nigra pars
      compacta DA neurons even though the A-type potassium current remains noticeably
      absent. These observations demonstrate that undifferentiated MN9D cells are not
      reasonable models of DA neurons. Although differentiated MN9D cells are closer to
      the mature DA neuronal phenotype, they do not fully mimic DA neurons and are
      likely to be of questionable value as a model because of their substantive
      differences, including the lack of the characteristic A-type potassium current.
      The future use of one or a combination of growth or other factors to
      differentiate MN9D cells may yield a more useful model system for Parkinson's
      disease studies in vitro.

PMID- 17028431
TI  - Distinct but overlapping functions for the closely related p190 RhoGAPs in neural
      development.
AB  - The p190 RhoGAPs, p190A and p190B, are highly related GTPase-activating proteins
      for the Rho GTPases. Rho GTPases and p190A reportedly control various aspects of
      brain development, and we hypothesized that p190B would be likewise involved in
      neuronal development. We find that like p190A, p190B is prominently expressed in
      the developing and adult brain. Unlike p190A, p190B is not abundantly tyrosine
      phosphorylated. We further demonstrate, using p190B-deficient mice, that p190B is
      required for normal brain development. Mice lacking p190B display several major
      defects, including (1) deficits in the formation of major forebrain commissures,
      including the corpus callosum and anterior commissure, (2) dilation of the
      lateral ventricles, suggesting inhibition of neurogenesis and/or survival, (3)
      thinning of the neocortical intermediate zone, suggesting defects in neuronal
      differentiation and/or axonal outgrowth, and (4) impaired neuronal
      differentiation. These defects are similar to, but distinct from, those described
      in p190A-deficient mice. RNA interference-mediated knockdown of neither p190
      protein results in significant inhibition of neurite outgrowth in neuroblastoma
      cells, despite an apparent increase in RhoA activity. We conclude that p190
      RhoGAPs control pivotal aspects of neural development, including neuronal
      differentiation and process outgrowth, and that these effects are mediated by
      signaling systems that include, but are not limited to, RhoA.

PMID- 17028432
TI  - Euglycemic hyperinsulinemia in severe sepsis and septic shock.
AB  - BACKGROUND: Recent studies have suggested that strict glucose control with
      intensive insulin therapy in critically ill patients may result in better
      outcomes. Whether this is also true in septic shock has not been determined. In
      addition, whether it is the insulin administration per se or the glucose control
      that contributes to the beneficial effects is unclear. We raised the hypothesis
      that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock
      due to peritonitis. MATERIALS AND METHODS: Fourteen anesthetized, mechanically
      ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight
      i.p. feces to induce sepsis. Ringer's lactate and 6% hydroxyethyl starch
      solutions were infused throughout the experiment to prevent hypovolemia. Two
      hours after feces injection, the animals were randomized to either an EH group (n
      = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40
      90 mg/dl), and potassium (to maintain the potassium level at 4.0- 5.5 mmol/l) or
      a control group (n = 7) with no intervention. All animals were studied until
      their spontaneous death or for 30 h. RESULTS: The EH group received a greater
      volume of 20% glucose, but blood glucose and potassium concentrations were
      similar in the two groups. No significant differences were found in hemodynamic
      variables. The circulating interleukin-6 levels increased in both groups after
      feces injection, but tended to be lower in the EH group (p < 0.05). The survival
      times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in
      the control group; p = 0.73). CONCLUSIONS: In this clinically relevant sheep
      septic shock model, EH decreased blood interleukin-6 concentrations but did not
      change hemodynamics or improve the outcome.

PMID- 17028433
TI  - Different protection mechanisms after pretreatment with glycine or alpha-lipoic
      acid in a rat model of warm hepatic ischemia.
AB  - BACKGROUND/AIM: Alpha-lipoic (LA) acid pretreatment has previously been described
      to reduce ischemia/reperfusion injury (IRI) after warm liver ischemia, whereas
      glycine pretreatment has been shown to be protective mostly in models of cold
      hepatic ischemia. The aim of this study was to determine whether glycine
      decreases IRI after warm hepatic ischemia. Furthermore we investigated whether
      doses of LA other than those used previously are also protective against IRI
      after warm hepatic ischemia. METHODS: Selective liver ischemia was maintained
      over a period of 90 min. In long-term as well as short-term experiments we
      studied IRI in several groups comparing animal survival as the pivotal endpoint.
      RESULTS: Animal survival was improved by glycine and 5,000 micromol LA, whereas
      all animals died within 3 days after pretreatment with 50 micromol LA. In the
      glycine group we observed a tendency towards decreased apoptosis-related cell
      death measured by the activity of caspase-3 in liver tissue and the percentage of
      TUNEL-positive hepatocytes in comparison to the untreated group. Serum alpha
      glutathione S-transferase, lipid peroxidation, and caspase-3 activity as well as
      the percentage of TUNEL-positive hepatocytes and the percentage of liver necrosis
      were only significantly decreased by 5,000 micromol LA pretreatment. Liver tissue
      levels of tumor necrosis factor (TNF)alpha were reduced only in the glycine group
      whereas TNFalpha was increased in the untreated as well as the LA group. Levels
      of TNFalpha mRNA were upregulated in both the glycine- and LA-pretreated groups.
      CONCLUSION: Our data show that increased animal survival by glycine was
      accompanied by a reduced TNFalpha content in liver tissue. Protection by glycine
      is likely to result from a reduction in adverse TNFalpha effects. Administration
      of high-dose LA on the other hand led to a significant reduction in necrosis- and
      apoptosis-related cell death in IRI of the liver without a reduction in liver
      TNFalpha.

PMID- 17028435
TI  - Evaluation of the risk factors for short-term mortality after acute ischemic
      stroke in the elderly: is there a role for nutritional risk assessment?

PMID- 17028434
TI  - Effective antitumoral immune responses are not induced by cytosine deaminase
      suicide gene transfer in a syngeneic rat pancreatic carcinoma model.
AB  - BACKGROUND: Experimental gene transfer can make tumors more immunogenic, leading
      to local regression and inducing immunological memory sufficient to permit
      resistance to a tumor rechallenge. However, this rarely had any significant
      impact on large established tumors. METHODS: To analyze potential immunological
      effects, we used weakly immunogenic pancreatic carcinomas in syngeneic,
      immunocompetent Lewis rats and performed in situ adenoviral mediated cytosine
      deaminase (CD) gene transfer followed by administration of the prodrug, 5
      fluorocytosine (5FC). In order to reflect the clinical situation, such treated
      tumors were surgically resected and animals were rechallenged with parental DSL6A
      pancreatic tumor cells. Tumor growth and cytotoxic activity of immune cells were
      determined. RESULTS: CD/5FC treatment of the DSL6A cells revealed significant
      induction of apoptosis in vitro and slowed down tumor progression in syngeneic
      hosts. Furthermore, we observed neither significant change in tumor growth nor
      protective immunity in the rechallenged animals. Analysis of T lymphocytes showed
      no specific cytotoxic activity against DSL6A cells. There was only a trend
      towards a minor NK cell activation. CONCLUSIONS: Albeit the present study failed
      to induce protective antitumor immunity, the initial finding of reduced tumor
      growth argues for the development of multimodal therapeutic options to overcome
      negative impacts of advanced malignant disease or chemotherapy-related anergy and
      immunosuppression.

PMID- 17028437
TI  - Nuclear factor-kappab (NF-kappaB): an unsuspected major culprit in the
      pathogenesis of endometriosis that is still at large?
AB  - Endometriosis, defined as the ectopic presence of endometrial glandular and
      stromal cells outside the uterine cavity, is a common benign gynecological
      disorder with an enigmatic pathogenesis. Many genes and gene products have been
      reported to be altered in endometriosis, yet some of them may not be major
      culprits but merely unwitting accomplices or even innocent bystanders. Therefore,
      the identification and apprehension of major culprits in the pathogenesis of
      endometriosis are crucial to the understanding of the pathogenesis and would help
      to develop better therapeutics for endometriosis. Although so far NF-kappaB only
      has left few traces of incriminating fingerprints, several lines of investigation
      suggest that NF-kappaB, a pivotal pro-inflammatory transcription factor, could
      promote and maintain endometriosis. Various inflammatory agents, growth factors,
      and oxidative stress activate NF-kappaB. NF-kappaB proteins themselves and
      proteins regulated by them have been linked to cellular transformation,
      proliferation, apoptosis, angiogenesis, and invasion. Interestingly, all existing
      and nearly all investigational medications for endometriosis appear to act
      through suppression of NF-kappaB activation. In endometriotic cells, NF-kappaB
      appears to be constitutively activated, and suppression of NF-kappaB activity by
      NF-kappaB inhibitors or proteasome inhibitors suppresses proliferation in vitro.
      Viewing NF-kappaB as a major culprit, an autoregulatory loop model can be
      postulated, which is consistent with existing data and, more importantly, can
      explain several puzzling phenomena that are otherwise difficult to interpret
      based on prevailing theories. This view has immediate and important implications
      for novel ways to treat endometriosis. Further research is warranted to precisely
      delineate the roles of NF-kappaB in the pathogenesis of endometriosis and to
      indict and convict its aiders and abettors.

PMID- 17028436
TI  - The obstetrical history in patients with Pfannenstiel scar endometriomas--an
      analysis of 81 patients.
AB  - INTRODUCTION: The participation of immune tolerance during pregnancy was
      suggested to be an important factor predisposing to the implantation of decidual
      cells after cesarean section in Pfannenstiel scar. Delivery at term is related to
      the termination of immune tolerance to fetal antigens that is maintained
      throughout pregnancy. Substantial proportion of cesarean section deliveries is
      performed before the onset of true term labor. The aim of this study was to
      analyze the clinical symptoms of spontaneous beginning of labor in pregnant women
      in whom cesarean sections were performed and in whom Pfannenstiel scar
      endometriomas were observed during follow-up. MATERIALS AND METHODS: We have
      retrospectively analyzed 81 patients following the surgical removal of scar
      endometrioma after cesarean section. Obstetrical histories of cesarean sections
      in the number of 5,370 preceding the occurrence of the scar endometrioma were
      analyzed. These data were collected in six different Gynecological and
      Obstetrical wards in Malopolska Province in Poland. Analysis of data was started
      by the retrospective evaluation of regular uterine contractions, uterine cervix
      ripening before cesarean section and the indications for surgery. RESULTS: In 67
      women from the group of 81 patients cesarean sections were performed with unripe
      uterine cervix and without the presence of regular uterine contractions. Elective
      indications for cesarean sections were predominant in this group of women. The
      relative risk of scar endometriomas occurrence following cesarean sections
      performed before onset of labor in comparison to cesarean sections following
      spontaneous onset of labor was statistically significantly higher [RR = 2.16, 95%
      CI = 1.21-3.83; OR = 2.18, 95% CI = 1.22-3.89]. CONCLUSIONS: Cesarean section
      performed before spontaneous onset of labor may increase substantially the risk
      of occurrence of scar endometriomas.

PMID- 17028438
TI  - Direct protection by a gonadotropin-releasing hormone analog from doxorubicin
      induced granulosa cell damage.
AB  - BACKGROUND/AIMS: Recent clinical applications suggest a beneficial effect of
      gonadotropin-releasing hormone analog (GnRHa) as a gonadal protector from
      chemotherapy-induced premature ovarian failure. This study aimed to determine
      cellular mechanisms involved in the protective action of GnRHa against granulosa
      cell damage caused by doxorubicin. METHODS: Granulosa cells were obtained by
      ultrasound-guided follicular aspiration from patients undergoing in vitro
      fertilization, and screened for GnRH receptor expression prior to analyses. The
      cellular function was assessed by measuring the conversion of exogenously
      supplied androstenedione to estradiol-beta (E2) in response to follicle
      stimulating hormone (FSH) (1 microM). RESULTS: Exposing to doxorubicin for 12 h
      before FSH stimulation caused a concentration-dependent inhibition of the E2
      secretion to a minimum level of 20% of control. When the cells were incubated
      with a GnRHa for 12 h before and during exposure to doxorubicin, granulosa cells
      produced an equal level of E2 to that of control cells. The protective action of
      GnRHa was dose-dependent; a half-maximal effect occurred at 10 nM. Preincubation
      with GnRHa alone had no effect on FSH-induced E2 production. CONCLUSION: These
      findings demonstrate that a GnRHa may retard doxorubicin-induced granulosa cell
      damage, suggesting an additional GnRH activity to protect the gonads during
      chemotherapy through GnRH receptor-mediated mechanism(s).

PMID- 17028439
TI  - Hypoglycaemia-insulin test: discordant growth hormone and cortisol response in
      paediatric patients regarding recovery from hypoglycaemia with or without oral
      glucose solution.
AB  - BACKGROUND: Hypoglycaemia-insulin test (HIT) is the 'gold standard' for the
      diagnosis of adrenal-pituitary-hypothalamic axis disorders. Controversy exists on
      the convenience of recovery from an insulin-induced hypoglycaemia since this test
      is not risk-free. OBJECTIVE: To ascertain whether recovery from insulin-induced
      hypoglycaemia with an oral glucose solution produces a different response of
      growth hormone (GH) and cortisol at different times of the study compared with
      spontaneous recovery from hypoglycaemia. PATIENTS AND METHODS: Prospective study
      of 100 children and adolescents with growth delay who underwent an HIT. Patients
      were consecutively assigned to two groups of 50. In one group recovery from
      hypoglycaemia occurred spontaneously and in the other recovery was achieved with
      an oral glucose solution (20 g of glucose) when glycaemia was under 30 mg/dl. The
      two groups did not differ in age, sex, pubertal status, weight, height and IGF-I
      levels. RESULTS: The response of GH at 30, 60, 90 and 120 min and cortisol at 10,
      60, 90 and 120 min was lower and statistically significant in patients with
      recovery from hypoglycaemia with oral glucose solution. GH deficiency was
      diagnosed more frequently in patients recovered with glucose solutions (94%)
      compared to those with spontaneous recovery (68%). CONCLUSIONS: Oral glucose
      solution administration when glycaemia was under 30 mg/dl in HIT produced a lower
      GH and cortisol response to insulin stimulus and a greater frequency of GH
      deficit diagnosis.

PMID- 17028441
TI  - Deterioration of visual acuity associated with growth hormone therapy in a child
      with extreme short stature and high hypermetropia.
AB  - BACKGROUND: Growth hormone (GH) has long been implicated in the pathogenesis of
      diabetic retinopathy, although its precise role remains ill-defined. In 1998, an
      association between exogenous human GH and retinal pathology in non-diabetic
      subjects was described. CASE REPORT: A female child with extreme short stature of
      unknown aetiology (height -7.38 SD at 11.3 years) and severe hypermetropia
      developed retinopathy with visual deterioration during two separate empiric
      trials of GH therapy. On the first occasion, a relatively high dose of GH (10.5
      mg/m2/week) administered from age 4.4 to age 4.7 years was associated with the
      development of central serous retinopathy, resulting in marked reduction in
      visual acuity. On cessation of GH, the macular oedema resolved, and visual acuity
      improved. At age 5.6 years, GH therapy was re-introduced at a lower dose (3.9
      mg/m2/week) and her vision monitored closely. Bilateral retinal oedema recurred
      after 3 months, and GH therapy was stopped. Once again, the macular oedema
      regressed, and visual acuity improved following withdrawal of GH. These
      ophthalmic changes contra-indicated further GH therapy. CONCLUSION: We suggest
      that GH may be a risk factor in the development of retinopathy in certain non
      diabetic patients, especially in the presence of a severe refractive error.

PMID- 17028440
TI  - Unique deletion in exon 5 of SHOX gene in a patient with idiopathic short
      stature.
AB  - BACKGROUND/AIM: It is known that haploinsufficiency for the SHOX gene (short
      stature homeobox gene on the X chromosome) is responsible for short stature in
      Turner syndrome and Leri-Weill dyschondrogenesis, and it has been reported that
      it is responsible for upwards of 1 in 50 cases of idiopathic short stature. SHOX
      haploinsufficiency is also associated with various radiographic abnormalities,
      such as coarse trabecular pattern, short metacarpals/metatarsals with metaphyseal
      flaring, altered osseous alignment at the wrist, radial/tibial bowing,
      triangularization of the radial head, abnormal tuberosity of the humerus, and an
      abnormal femoral neck. Shortening and bowing of the radius and dorsal dislocation
      of the distal ulna characterize the Madelung deformity. These characteristic
      findings led us to do a study assessing the predictive value of certain
      radiographic features in association with genetic markers of idiopathic short
      stature. METHODS: Here we describe a case of a Hispanic male with idiopathic
      short stature and Madelung deformity with a novel mutation in the SHOX gene.
      RESULTS: Additional studies revealed a strong family history of short stature and
      the same SHOX mutation segregating from the mother. CONCLUSION: This case
      resulted in the description of a novel mutation in exon 5 (M202delA) and suggests
      the importance of screening for SHOX mutations in patients with idiopathic short
      stature with subtle radiographic abnormalities, including the components of the
      Madelung deformity in their bone age films.

PMID- 17028442
TI  - Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese
      patients with cryptorchidism.
AB  - BACKGROUND/AIMS: Although insulin-like factor 3 (INSL3) and its receptor leucine
      rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor
      affecting testis descent (LGR8/GREAT) are essential for the gubernacular
      development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with
      cryptorchidism (CO), and there is no report documenting a positive association of
      CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the
      relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development
      of CO. METHODS: Sixty-two Japanese CO patients and 60 fertile males were studied.
      INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and
      LGR8/GREAT was examined by denaturing high-performance liquid chromatography
      followed by direct sequencing for exons with abnormal chromatogram patterns.
      RESULTS: No definitive mutation was identified in both genes. Six polymorphisms
      were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr
      polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3,
      95% confidence interval=1.7-17). CONCLUSION: The results, in conjunction with the
      previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and
      that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a
      susceptibility factor for the development of CO.

PMID- 17028443
TI  - The quail mesonephros: a new model for renal senescence?
AB  - BACKGROUND/AIMS: Renal senescence during normal aging is associated with specific
      vascular alterations and tissue degeneration. Although the degenerative program
      executed during embryonic kidney development is known to include vascular
      alterations, studies yet have to examine whether it involves replicative
      senescence. In this study, we assessed the potential of the quail mesonephros, a
      transitory embryonic kidney, as a model of human renal senescence. METHODS: Quail
      embryos with developing or degenerating mesonephros were studied on day 6 or day
      11 of incubation, respectively. Senescence-associated beta-galactosidase
      activity, a marker of replicative senescence, was examined on whole mounts and
      sections. Senescent vascular characterization was performed by the scanning
      electron-microscopic analysis of vascular corrosion casts. RESULTS: Senescence
      associated beta-galactosidase activity was found only in old mesonephros.
      Moreover, at 11 days of incubation glomerular capillaries showed discontinuities
      and were thinner and more tortuous than those observed at 6 days, characteristics
      also reported for the aging human kidney. CONCLUSION: The degenerating quail
      mesonephros is a potential model of renal senescence, showing biochemical and
      morphological characteristics of the aging human kidney.

PMID- 17028444
TI  - Altered expression of matrix-related molecules in the development of chronic
      Thy1.1 nephritis.
AB  - BACKGROUND/AIM: Matrix production and degradation are critically important in
      chronic nephritis. Our aim was to investigate the precise expression of matrix
      related molecules which is essential for understanding the pathogenesis of renal
      disease. METHODS: Chronic nephritis was induced by a single injection of anti
      Thy1.1 antibody to unilaterally nephrectomized rats. RNA was extracted from renal
      cortex and isolated glomeruli 4, 7, and 10 weeks after the antibody injection.
      Matrix-related gene expressions were measured by polymerase chain reaction. The
      expression of alpha1(IV) and alpha3(IV) collagens was studied by
      immunohistochemistry. The gelatinolytic activity in the glomeruli was assayed by
      gelatin zymography. RESULTS: Polymerase chain reaction revealed an increase of
      alpha1(IV) in both glomeruli and renal cortex from nephritic rats. In contrast,
      the expression of alpha3(IV), normally a component of the glomerular basement
      membrane, was decreased in nephritic animals. Immunohistochemistry confirmed the
      finding that alpha1(IV) and alpha3(IV) were up- and downregulated, respectively,
      in the glomeruli. Gene expression and activity of matrix metalloproteinase 2 were
      enhanced, while those of matrix metalloproteinase 9 were clearly suppressed in
      nephritis. CONCLUSIONS: Downregulation of alpha3(IV) and enhancement of the
      matrix metalloproteinase-2 activity in the glomeruli may contribute to the
      glomerular damage by altering the glomerular basement membrane components.
      Impairment of the glomerular basement membrane integrity may possibly be
      implicated in irreversible renal dysfunction.

PMID- 17028445
TI  - Serum ghrelin and cholesterol values in suicide attempters.
AB  - In our previous study, we demonstrated that suicide attempters had statistically
      significant lower leptin and cholesterol levels compared with healthy controls.
      In keeping with our previous report regarding lower serum cholesterol and leptin
      levels in suicide attempters compared with healthy controls, the relationship
      between cholesterol and leptin, and ghrelin, we aimed to evaluate serum total
      cholesterol and ghrelin levels in suicide attempters. In the present study, 30
      patients with suicide attempts (aged 18-47 years) and the same number of healthy
      controls were compared with regard to serum total cholesterol and ghrelin levels.
      The mean cholesterol level of the patients was significantly lower than that of
      the controls. On the other hand, the suicide attempters had significantly higher
      ghrelin levels compared with the controls. The results suggest that suicide
      attempts seem to be associated with decreased serum cholesterol and higher
      ghrelin values.

PMID- 17028447
TI  - Nitric oxide and neopterin in bipolar affective disorder.
AB  - BACKGROUND: There is an increasing interest in the role of nitric oxide (NO) and
      pterines in the pathophysiology of neuropsychiatric disorders. The results so far
      show an inconsistent pattern. METHODS: In the present study, neopterin and a
      measure of NO synthesis in plasma of symptomatic and euthymic bipolar affective
      patients were compared to those of patients with a major depression and healthy
      controls. As an index of NO synthesis, the ratio of the amino acids citrulline
      and arginine (Cit-Arg ratio) was calculated. Neopterin is a bypass product in the
      synthesis of tetrahydrobiopterin, which is a cofactor of NO synthase. RESULTS:
      The results indicate that both neopterin and the Cit-Arg ratio are decreased in
      bipolar affective patients, irrespective of their symptomatic status. In
      addition, an association between the values of the Cit-Arg ratio and the
      neopterin level was observed, which is suggestive for a low tetrahydrobiopterin
      activity. CONCLUSION: NO formation may be endangered in bipolar affective
      disorder.

PMID- 17028446
TI  - Constitutional downregulation of SEMA5A expression in autism.
AB  - There is strong evidence for the importance of genetic factors in idiopathic
      autism. The results from independent twin and family studies suggest that the
      disorder is caused by the action of several genes, possibly acting epistatically.
      We have used cDNA microarray technology for the identification of constitutional
      changes in the gene expression profile associated with idiopathic autism. Samples
      were obtained and analyzed from 6 affected subjects belonging to multiplex autism
      families and from 6 healthy controls. We assessed the expression levels for
      approximately 7,700 genes by cDNA microarrays using mRNA derived from Epstein
      Barr virus-transformed B lymphocytes. The microarray data were analyzed in order
      to identify up- or downregulation of specific genes. A common pattern with nine
      downregulated genes was identified among samples derived from individuals with
      autism when compared to controls. Four of these nine genes encode proteins
      involved in biological processes associated with brain function or the immune
      system, and are consequently considered as candidates for genes associated with
      autism. Quantitative real-time PCR confirms the downregulation of the gene
      encoding SEMA5A, a protein involved in axonal guidance. Epstein-Barr virus should
      be considered as a possible source for altered expression, but our consistent
      results make us suggest SEMA5A as a candidate gene in the etiology of idiopathic
      autism.

PMID- 17028448
TI  - The serotonin transporter gene: polymorphism and haplotype analysis in Russian
      suicide attempters.
AB  - The focus on gender-specific genes associated with female suicide is justified by
      the possible dimorphic nature of the serotonergic system and by the greater
      number of suicide attempts in females. We performed analysis of the promoter (5
      HTTLPR) and intron 2 (STin2 VNTR) polymorphisms and haplotypes of the serotonin
      transporter gene in Russian suicide attempters, separately in men and women. Our
      findings indicate the contribution of the SLC6A4 gene to susceptibility for
      suicidal behavior in women, but not in men. The L/L genotype (p = 0.013, OR =
      2.09) and L10 haplotype (p = 0.04, OR = 1.77) were associated with suicide in
      Russian women only. Further investigations of this gene in different phenotypic
      groups are necessary.

PMID- 17028449
TI  - Association of eating disorders with catechol-o-methyltransferase gene functional
      polymorphism.
AB  - AIM: The aim of this study was to evaluate functional catechol-O
      methyltransferase (COMT) genetic variation as a risk factor for eating disorders
      (ED). METHOD: Eighty women receiving treatment for serious ED (52 for anorexia
      nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group
      underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low
      activity allele and the high-activity allele (H) were determined. RESULTS: The
      H/H genotype was twice as frequent in the ED group as in the control group (52.5%
      in the ED group and 25% in controls, chi(2) = 15.5, d.f. = 2, p < 0.001, odds
      ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients
      (chi(2) = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio =
      4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison
      to 47.8% of patients from the control group (chi(2) = 13.89, p < 0.001, odds
      ratio = 6.088). In the anorexia group, H allele frequency was enhanced even
      higher (70.2 vs. 47.8%, chi(2) = 14.48, p < 0.001, odds ratio = 8.175). The
      genotype associations in the subgroup of bulimia patients were not significant,
      but a trend for a higher frequency of the H allele was found (p = 0.084, odds
      ratio = 5.309). CONCLUSIONS: These findings seem to suggest that a turnover of
      catecholamines, connected with polymorphism determining high activity of COMT
      enzyme, is connected with the risk of ED occurrence, particularly anorexia
      nervosa. The risk is significantly higher for women with an allele of higher
      activity.

PMID- 17028450
TI  - Assessment of cancer-related pain.

PMID- 17028451
TI  - The burden of pain of inpatients undergoing radiotherapy--discrepancies in the
      ratings of physicians and nurses.
AB  - BACKGROUND: The aim of this study was to rate the burden of pain of cancer
      patients receiving radiotherapy from the point of view of the patients themselves
      as well as the physicians and nurses caring for the patient, and to examine
      possible differences in the ratings. PATIENTS AND METHODS: 68 cancer patients
      received a pain questionnaire about pain intensity and subjective well-being. At
      the same time, physicians and nurses answered 7 pain-related questions about each
      patient. RESULTS: 34% of the patients reported strong or very strong pain in the
      past week, 8% even unbearable pain. 66% felt psychologically distressed, 70%
      developed anxiety because of pain. 74% believed that pain is an essential part of
      the disease. Nurses and physicians often underestimate patients' burden of pain.
      Nevertheless, the rating of the nurses is more accurate than that of the
      physicians. CONCLUSION: Physicians and nurses often underestimate pain intensity.
      It seems that several patients are unable or unwilling to express their pain or
      that therapists lack adequate methods of pain assessment. To optimize pain
      treatment, communication between patients, physicians and nurses needs to be
      improved.

PMID- 17028452
TI  - Retrospective analysis of CD38 expression in 102 patients with B-CLL with a
      maximum follow-up of 18 years: incidence and prognostic significance.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of CD38
      expression in all CLL patients of our institution and to determine its prognostic
      significance in correlation with other parameters of the disease. PATIENTS AND
      METHODS: We analyzed the CD38 expression in 102 B-CLL patients referred to our
      department over a period of 12 months. RESULTS: The follow-up period ranged from
      0 to 18 years. 30 patients (29%) were CD38-positive (CD38+) and 72 patients (71%)
      were CD38-negative (CD38-) with a median age of 65 and 64 years, respectively. Of
      the Binet A patients (77), 25% showed an expression of CD38; in Binet B/C
      patients (25), 67% expressed CD38. Median survival of the CD38- group was 77.5
      months and of the CD38+ group 56.3 months. CD38 expression was associated with
      shorter lymphocyte doubling time (p < 0.0001), a more advanced stage of the
      disease, and a shorter therapy- and progression-free time (p < 0.0017/p <
      0.0012), which was also true in the Binet A subgroup. In 2 cases, we detected a
      shift from the CD38- to the CD38+ phenotype. CONCLUSION: We found a low incidence
      of CD38+ CLL patients, and CD38 expression predicted significantly a more
      advanced stage of the disease, shorter lymphocyte doubling time and shorter
      therapy- and progression-free time.

PMID- 17028453
TI  - PAC fixed dose: pharmacokinetics of a 1-hour paclitaxel infusion and comparison
      to BSA-normalized drug dosing.
AB  - BACKGROUND: The aim of this study was to determine the pharmacokinetics (PKs) of
      a 175-mg fixed dose of paclitaxel (PAC) after a 1-h infusion in cancer patients
      and to compare them with the PK parameters from a study with a dose normalized to
      the body surface area (BSA) (100 mg/m2). PATIENTS AND METHODS: PAC PKs were
      studied during the first course of therapy in 13 patients. A fixed dose of 175 mg
      PAC was administered weekly by a 1-h infusion to patients with advanced cancer.
      Total PAC in serum was quantified by high-performance liquid chromatography
      (HPLC). PK parameters were calculated by non-compartmental and model-dependent
      methods. RESULTS: The mean BSA of 12 patients (1 patient excluded from all
      analyses because of prolonged infusion duration) was 1.79 m2 (coefficient of
      variation (CV) 7.8%), the mean dose referred to the individual BSAs was 98.3
      mg/m2 (CV 8.3%). The mean area under the curve (AUC) was 6,193 ng/ml x h (CV
      46%), the mean plasma clearance (Clp) was 19.7 l/h/m2 (CV 45%), and the volume of
      distribution at steady state (Vss) was 121.6 l/m2 (CV 52%). The mean residence
      time (MRT) was 7.6 h (CV 46%), the mean distribution half-life (t1/2 alpha) of
      PAC(tot) was 0.4 h (CV 62%), and the elimination half-life (t1/2 beta) 10.0 h (CV
      42%). Maximum plasma concentration Cmax was 3,161 ng/ml (CV 36%). The mean time
      above 0.05 microM (42.7 ng/ml) was 19.7 h, and the mean time above 0.1 microM
      (85.4 ng/ml) was 10.6 h. CONCLUSIONS: In this study, a fixed dose of PAC of 175
      mg corresponds to a mean BSA-normalized dose of 98.3 mg/m2 (range 88.8-117.4
      mg/m2). A higher variability of PK parameters was observed compared to previously
      published results of a PK study with BSA-normalized dosing of 100 mg/m2. However,
      the AUC and the time above threshold concentrations did not depend on the dose.
      Therefore, a fixed dose of 175 mg weekly could be an option for palliative
      treatment with PAC and may offer a simple but effective schedule for PAC
      treatment.

PMID- 17028454
TI  - Primary central nervous system lymphoma in an Asian population: a 15-year
      experience.
AB  - BACKGROUND: The aim of this study was to characterize primary central nervous
      system lymphoma (PCNSL) among Asian patients and to determine their outcomes with
      different therapeutic modalities. PATIENTS AND METHODS: Between 1990 and 2005, 37
      patients with PCNSL were analyzed within 5 different treatment groups:
      radiotherapy alone (arm A), combined chemoradiation (arm B), chemotherapy alone
      with methotrexate (MTX) > or = 1 g/m2 (arm C), miscellaneous therapy (arm D), and
      best supportive care (arm E). RESULTS: The median age at presentation was 59
      years, and the majority of patients were male (68%). All patients had aggressive
      diffuse large B-cell lymphoma. The number of patients in arms A to E were 6, 16,
      3, 8 and 4, respectively. The overall median survival was 7.4 months, 54.1
      months, not reached, 8.9 months and 0.9 months, respectively. Use of MTX 1-2.5
      g/m2 per cycle and an ECOG performance status of 0-2 were each associated with
      improved survival on univariate analysis (p = 0.022 and p = 0.049, respectively).
      Compared to radiotherapy alone, use of combined chemo-radiation was associated
      with a trend towards improved overall median survival (7.4 vs. 54.1 months, p =
      0.058). CONCLUSION: The clinical characteristics and treatment outcomes in our
      Asian patients were comparable to those reported in Western series. Use of MTX 1
      2.5 g/m2 per cycle and an ECOG performance status of 0-2 were associated with
      improved survival.

PMID- 17028455
TI  - Verrucous carcinoma of the temporal bone and maxillary antrum: two unusual
      presentations of a rare tumor.
AB  - BACKGROUND: Verrucous carcinoma (VC) is a low-grade variant of squamous cell
      carcinoma. The involvement of the temporal bone and maxillary antrum is very
      rare. PATIENTS AND METHODS: The clinicopathologic features of 2 such tumors are
      reported, and the pertinent literature is reviewed. RESULTS: In the 2 patients,
      the diagnostic procedure was complicated due to initial inconclusive histology.
      Both were treated with concomitant radiochemotherapy. They were free of disease
      for 5.8 and 11 years after diagnosis. An additional 15 cases of VC of the
      temporal bone and 10 cases of maxillary antrum tumors have been reported in the
      literature. In 10 patients, multiple biopsies were required, and in 7 patients, a
      definitive histological diagnosis was not obtained before surgery. The disease
      reappeared in 8 out of 15 patients treated solely with surgery. Only 2 of them
      were salvaged by reoperation. Radiochemotherapy only (without any surgery) was
      successfully used in 4 patients. CONCLUSIONS: VC of the temporal bone or
      maxillary antrum is an extremely rare tumor. For reliable histological diagnosis,
      multiple biopsies of deep and ample tissue samples are mandatory. Surgery is a
      mainstay of therapy; however, radiochemotherapy also represents a viable
      treatment option with curative potential.

PMID- 17028456
TI  - Leukocytoclastic vasculitis and acute renal failure after influenza vaccination
      in an elderly patient with myelodysplastic syndrome.
AB  - BACKGROUND: Influenza vaccination is recommended for individuals over 65 years of
      age and for all patients with chronic diseases who are at risk. Side effects
      which are seen in 1-10% of the vaccinated individuals are usually mild and
      consist of local reactions and constitutional symptoms. Since 1974, about 30
      cases of vasculitis following influenza vaccination have been reported. CASE
      REPORT: We here describe a 70-year-old male patient with a 5-year history of
      myelodysplastic syndrome, who had received continuous steroid treatment since
      2004 and presented with leukocytoclastic vasculitis and acute renal failure
      requiring hemodialysis therapy 1 week after influenza vaccination. High-dose
      steroid treatment was promptly initiated, but hemodialysis was needed for 9 days.
      Maintained steroid treatment for 2 weeks was associated with complete recovery of
      renal function and skin lesions. CONCLUSION: As influenza vaccination is
      increasingly used, physicians should be aware of the potential serious side
      effect of leukocytoclastic vasculitis, particularly in patients who are
      immunocompromised either due to an underlying disorder or as a treatment-related
      side effect.

PMID- 17028457
TI  - Cancer and thrombosis: managing the risks and approaches to thromboprophylaxis.
AB  - Patients with cancer are at increased risk of venous thromboembolism (VTE)
      compared with patients without cancer. This results from both the prothrombotic
      effects of the cancer itself and iatrogenic factors, such as chemotherapy,
      radiotherapy, indwelling central venous devices and surgery, that further
      increase the risk of VTE. Although cancer-associated thrombosis remains an
      important cause of morbidity and mortality, it is often underdiagnosed and
      undertreated. However, evidence is accumulating to support the use of low
      molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients
      with cancer. Not only have LMWHs been shown to be at least as effective as
      coumarin derivatives in this setting, but they have a lower incidence of
      complications, including bleeding, and are not associated with the practical
      problems of warfarin therapy. Furthermore, a growing number of studies indicate
      that LMWHs may improve survival among patients with cancer due to a possible
      antitumor effect. Current evidence suggests that LMWHs should increasingly be
      considered for the longterm management of VTE in patients with cancer.

PMID- 17028458
TI  - Schwa elision in fast speech: segmental deletion or gestural overlap?
AB  - Pretonic schwa elision in fast speech (e.g. potato --> [pt]ato, demolish -->
      [dm]olish) has been studied by both phonologists and phoneticians to understand
      how extralinguistic factors affect surface forms. Yet, both types of studies have
      major shortcomings. Phonological analyses attributing schwa elision to across-the
      board segmental deletion have been based on researchers' intuitions. Phonetic
      accounts proposing that elision is best characterized as gestural overlap have
      been restricted to very few sequence types. In this study, 28 different [#CeC-]
      sequences are examined to define appropriate acoustic criteria for 'elision', to
      establish whether elision is a deletion process or the endpoint of a continuum of
      increasing overlap, and to discover whether elision rates vary for individual
      speakers. Results suggest that the acoustic patterns for elision are consistent
      with an overlap account. Individual speakers differ as to whether they increase
      elision only at faster speech rates, or elide regardless of rate. Phonotactic
      legality per se does not affect elision rates, but speech rate may affect the
      phonological system by causing a modification of the standard timing
      relationships among gestures.

PMID- 17028459
TI  - Testing licensing by cue: a case of Russian palatalized coronals.
AB  - The hypothesis 'licensing by cue' by Steriade holds that phonological contrasts
      are maintained in environments that provide better acoustic cues to the contrasts
      and are neutralized in environments that provide poorer acoustic cues or no cues.
      This paper tests the hypothesis by examining the distribution of a phonological
      contrast--the Russian plain/palatalized coronal stops /t/ and /tj/ in various
      syllable-final contexts. The results of a series of acoustic and perceptual
      experiments presented in this paper provide some support for the hypothesis: the
      relative salience of releases in different word boundary contexts (_#k > _#n,
      _#s) correlates strongly with the general patterns of neutralization of the
      contrast in similar word-internal contexts (_k > _n, _s) in Russian and other
      related languages. At the same time, the relative salience of VC transitions in
      different vowel contexts (a_ > u_ > i_) has apparently little to do with attested
      patterns of neutralization. The results suggest that some perceptual cues are
      phonologically more relevant than others, providing evidence for interactions
      between phonetics and phonology more complex than predicted by the hypothesis.

PMID- 17028460
TI  - On the prosody of Orkney and Shetland dialects.
AB  - The aim of this study is to find experimental support for impressionistic claims
      that there are prosodic differences between the dialects of Orkney and Shetland.
      It was found that native listeners had no difficulty in discriminating between
      Orkney and Shetland dialects when presented with speech fragments containing only
      melodic information. The results of a subsequent acoustic investigation revealed
      that there is a striking difference in pitch-peak location, which can be
      characterised as a shift in the location of the entire rise, i.e. both the onset
      and the peak. Shetland has early alignment, whereas the accent-lending rise in
      Orkney occurs late, so that in disyllabic words with initial stress the pitch
      peak does not coincide with the stressed syllable, but is delayed until the post
      stress syllable. Finally, the perceptual relevance of the prosodic parameters
      identified in the acoustic study was investigated.

PMID- 17028461
TI  - Prosodic shaping of consonant gemination in Cypriot Greek.
AB  - This paper presents an experimental investigation of durational variation in
      lexical and post-lexical geminate alveolar laterals, under different stress
      conditions, in Cypriot Greek. Lexical geminates are found to be longer than post
      lexicals, and both geminates and non-geminates are longer in word-initial
      position. The durational distinction is robust in all conditions, but
      particularly for word-initial lexical geminates. Post-lexical geminates and word
      initial lexical geminates are significantly longer when pre-stress. Word-initial
      geminates are longer when preceded by a word-final nasal (the condition for post
      lexical gemination), thus creating a kind of 'supergeminate' consonant and
      indicating that word-final nasals are not deleted, as has previously been thought
      to be the case. Implications for the phonological analysis of Cypriot Greek
      geminates and the role of prosodic and phonotactic restrictions are considered.

PMID- 17028464
TI  - High level of expression of alpha-fetoprotein receptor in gastric cancers.
AB  - The expression of the receptor for alpha-fetoprotein (AFP-R) was examined
      immunohistochemically in 47 cancer and 14 benign human gastric tissues. Rabbit
      polyclonal antibody against human AFP-R was used for immunohistochemical
      staining. Thirty-four of the 47 cancer tissues expressed AFP-R showing granular
      or reticular staining on the cancer cell surface, while only 2 of 61 control
      cases (14 benign gastric tissues and 47 nonmalignant tissues adjacent to cancer)
      showed faint and homogeneous staining in the cytoplasm of noncancerous cells.
      There was a significant difference in staining intensity between the cancerous
      and noncancerous groups. However, no statistically significant difference in
      staining intensity was found among the groups of well-differentiated, moderately
      differentiated and poorly differentiated adenocarcinomas. On the other hand, the
      staining intensity of signet ring cell carcinoma was significantly weaker than
      that of the three adenocarcinoma groups. The high level of AFP-R expression in
      gastric cancers may allow the use of AFP-R as a new clinically useful marker of
      gastric cancer in the tissue level.

PMID- 17028465
TI  - Do serum angiogenic growth factors provide additional information to that of
      conventional markers in monitoring the course of metastatic breast cancer?
AB  - OBJECTIVE: Our work evaluated the potential role of basic fibroblast growth
      factor (bFGF) and vascular endothelial growth factor (VEGF) serum levels with
      respect to that of conventional serum tumour markers, CEA and CA 15-3, in
      monitoring the course of metastatic breast cancer in 56 female patients treated
      with cytotoxic chemotherapy. METHODS: VEGF and bFGF concentrations were
      determined using a quantitative sandwich enzyme immunoassay technique. The
      positive predictive value (PPV) of each marker and of marker combinations for
      different types of clinical response was calculated. RESULTS: The highest PPV for
      overall disease control was shown by bFGF (70%), which also showed the highest
      PPV for both partial response (36.4%) and stable disease (63.2%). CEA showed the
      highest predictive value for progression (69.2%). A combined increase in CEA and
      bFGF or VEGF was associated with disease progression in all patients.
      CONCLUSIONS: Information provided by angiogenic factor levels seems to be
      independent of and is possibly complementary to that provided by conventional
      serum markers. bFGF showed the maximum predictive value for disease control and
      provided additional information to that obtained from CEA or CA 15-3 evaluation.
      It could therefore be a promising candidate for monitoring response to
      chemotherapy in advanced breast cancer.

PMID- 17028466
TI  - [Hemolysis, elevated liver enzymes, and low platelet count syndrome].
AB  - HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome is a
      severe, life-threatening pregnancy pathology, which occurs in 0.2-0.8% of all
      pregnancies, and approximately 10% (2-20%) of pregnancies are complicated with
      severe preeclampsia. This syndrome usually develops in the third trimester of
      pregnancy in preeclamptic patients, sometimes it occurs in the second trimester
      of pregnancy, and very rarely HELLP syndrome may develop within 48-72 hours after
      delivery. Diagnosis is complicated as there are no specific clinical signs,
      therefore, this syndrome may be confused with other pathologies like acute fatty
      liver of pregnancy, idiopathic thrombocytopenia, hemolytic uremic syndrome,
      appendicitis, and etc. The patients with HELLP syndrome should be treated in the
      tertiary care hospital, where appropriate diagnostics and multidisciplinary help
      for mother and fetus can be assured. When the syndrome was described for the
      first time, L. Weinstein recommended prompt delivery as the only possible
      treatment. Current studies show that conservative treatment of patients with
      HELLP syndrome is safe, without an increase in morbidity and mortality. That is
      why now many authors agree that treatment approach should be based on the
      estimated gestational age and the condition of the mother and fetus.

PMID- 17028467
TI  - [Empiric de-escalation strategy of antibiotic treatment].
AB  - Nosocomial pneumonia, especially ventilator-acquired pneumonia, has the greatest
      impact on patients' management in intensive care unit. Inappropriate initial
      antimicrobial treatment increases attributable and crude mortality from
      ventilator-acquired pneumonia. De-escalation therapy improves short-term survival
      of patients with ventilator-acquired pneumonia without increasing the emergence
      of resistant organisms.

PMID- 17028468
TI  - Measurement of quality of life in stroke patients.
AB  - The quality of life after stroke and the methods of measuring this aspect of the
      disease have been viewed with a growing interest. The measurement has been
      focused on the physical, psychological, social, and functional aspects of living
      and is generally based on the patients' subjective perception of his/her general
      health and well-being. Seven generic measurement scales and three recently
      developed stroke-specific scales have been assessed and discussed. The stroke
      specific quality of life measures described in this review are as follows: the
      Stroke Adapted Sickness Impact Profile, the Stroke Impact Scale, and the Stroke
      Specific Quality of Life Measure. The various factors leading to a deterioration
      of the quality of life and influencing the quality of life scores are discussed
      and defined. Moreover, the necessity of further research is stressed.

PMID- 17028469
TI  - [Evaluation of the cosmetic effect of orbital endoimplantation after removal the
      eyeball].
AB  - The purpose of our study was to evaluate the cosmetic effect of endoimplantation
      after removal the eyeball. The removal of the globe creates anatomic and
      physiological alteration of the orbital tissue and orbital bones. A volume
      deficit occurs when an eye is enucleated. Deep upper lid sulcus, ptosis, lower
      lid laxity, and enophthalmus of the artificial eye together constitute the
      postenucleation socket syndrome, which creates an asymmetry of the face. The
      orbital prosthesis by placing it in the orbital cavity allows correcting volume
      deficit, so the implant with attached extraocular muscles, together with an
      artificial eye, creates an illusion of real eye. Forty patients were operated on
      in Clinic of Eye Diseases of Kaunas University of Medicine Hospital. Twenty
      patients underwent removal of the eye and procedure of orbital implant insertion
      (main group). Twenty patients had just an eyeball removal without insertion of an
      orbital implant (control group). There was a statistically significant difference
      in exophthalmometry data between main and control groups (14.20+/-2.73 vs.
      10.35+/-1.23 mm, respectively; p<0.05). The motility of artificial eye laterally
      (4.30+/-1.66 mm), medially (3.65+/-1.23 mm), up (3.70+/-1.13 mm), and down
      (3.40+/-1.19 mm) in the main group was significantly better as compared to the
      control group (p<0.05), where motility of the artificial eye was 0.60+/-0.68 mm
      laterally, 0.70+/-0.92 mm medially, 0.30+/-0.66 mm up, and 0.30+/-0.47 mm down.
      Therefore, a much better symmetry, better movement of the artificial eye, and
      less severe form of postenucleation syndrome were observed in patients who
      underwent orbital endoimplantation after eyeball removal.

PMID- 17028470
TI  - New surgical technique for the treatment of urinary incontinence in Clinic of
      Obstetrics and Gynecology of Kaunas University of Medicine.
AB  - There are various surgical methods for the treatment of female urinary stress
      incontinence. The aim of this study was to evaluate the effectiveness of tension
      free vaginal tape (TVT) operation based on a three-year clinical experience and
      the possibility of its use in the outpatient settings. MATERIALS AND METHODS: The
      patients were examined according to a standardized protocol for urinary
      incontinence and were operated on according to the original "Gynecare TVT"
      protocol. A total of 57 women were operated on and followed up during the study
      period (02/25/2000-12/31/2002). The average age was 52 years. Out of them 31
      (54.4%) women were after menopause and 56 (97.9%) gave birth. Nine women had
      operations in their medical histories: five had hysterectomies and the other four
      were operated on because of urinary incontinence. Besides, five women were
      operated due to mixed urinary incontinence. Among the operated women, 6 had local
      anesthesia, 13 had epidural, and 38 had lumbar anesthesia. The average time of
      the operation was 22.3 minutes. The mean hospital stay was 4.4 days. Five
      patients were hospitalized for one day. Besides TVT operation, eight patients had
      anterior colporrhaphy, two patients had posterior colporrhaphy, and two patients
      had "mesh" application for cystocele treatment. RESULTS: One woman had stress
      urinary incontinence symptoms after operation (the effectiveness of operation was
      98.2%). The main complications were: perforation of the urinary bladder was
      present in 1 (1.8%) patient and infection of urinary tract - in 4 (7.0%)
      patients. CONCLUSION: TVT operation is a minimal invasive, fast, safe and very
      effective surgical procedure for the treatment of urinary stress incontinence,
      which has to be implemented in Lithuania as a routine outpatient procedure.

PMID- 17028471
TI  - [Evaluation of factors influencing effectiveness of kinesitherapy in patients
      after traumatic brain injury].
AB  - OBJECTIVE OF THE STUDY: To establish the factors, which have an influence on
      recovery of motor and cognitive functions in patients after moderate or severe
      traumatic brain injury, when kinesitherapy is applied during the acute stage of
      injury and early stage of rehabilitation. MATERIAL AND METHODS: Subjects were 131
      patients (99 men and 32 women) with a mean age of 39.5+/-15.9 years. Patients
      were divided into two subgroups according to degree of injury: severe injury (103
      subjects) and moderate injury (28 subjects). During acute stage of injury,
      patients were treated at the Unit of Brain Injuries, Kaunas University of
      Medicine Hospital; thereafter, 80 patients continued rehabilitation at the Unit
      of Neurorehabilitation, while 51--in another rehabilitation centers. Recovery of
      motor and cognitive functions was evaluated using Functional Independence
      Measure: during acute stage of injury (beginning and end) and during early stage
      of rehabilitation (beginning, day 25, and end). RESULTS: In order to determine
      the effect of kinesitherapy, the influence of following factors was evaluated:
      meningitis, cranial nerves damage, musculoskeletal system dysfunctions, plegia of
      extremities, speech and cognitive dysfunctions, behavioral changes, sleep
      disorders, depression, pneumonia, edema, hydrocephalus, epilepsy. The motor score
      in patients after moderate traumatic brain injury at the beginning of acute stage
      was 32.4+/-12.7, while in patients after severe injury it was 21.3+/-7.7
      (p<0.01). At the end of this stage, the difference between subgroups was
      insignificant: 61.8+/-24.0 and 60.9+/-22.5, respectively (p>0.05). At the
      beginning of acute stage of injury, cognitive function score differed
      significantly: in moderate injury subgroup, the score was 14.2+/-5.5, while in
      severe injury subgroup - 10.0+/-4.9 (p<0.01). At the end of early stage of
      rehabilitation, no significant difference in cognitive function scores was found
      between subgroups: 22.3+/-8.4 and 22.5+/-8.6 scores, respectively (p>0.05).
      CONCLUSIONS: Insufficient recovery of motor functions during period of
      kinesitherapy was influenced by depression, pneumonia, plegia of extremities,
      speech and cognitive dysfunctions, sleep disorders, dysfunctions of
      musculoskeletal system, behavioral changes, while the recovery of cognitive
      functions was influenced mainly by pneumonia, speech and cognitive dysfunctions,
      and sleep disorders (p<0.05).

PMID- 17028472
TI  - The relationship of the intensity of lens opacity with physical activity.
AB  - OBJECTIVE: To study the character and the intensity of lens opacity and the
      visual acuity in cataract patients and controls and to determine the association
      of these indices with the subjects' physical activity. MATERIAL AND METHODS: The
      lens opacity in 110 eyes of patients (n=110) aged 60.3+/-0.4 (mean+/-SEM) years
      admitted to the Clinic of Eye Diseases of Kaunas University of Medicine Hospital
      for cataract surgery and the lens opacity of 100 eyes of controls (n=50) aged
      59.8+/-0.4 (mean+/-SEM) (p>0.05) years hospitalized in the Clinic of Skin and
      Venereal Diseases was evaluated according to the Lens Opacity Classification
      System, version III. Visual acuity was investigated using the Snellen chart.
      Physical activity in metabolic equivalent minutes per week (MET-minutes/week) was
      evaluated according to the International Physical Activity Questionnaire.
      RESULTS: The means of the intensity of lens opacity of patients with cataract
      were significantly higher, and the means of visual acuity and physical activity
      were significantly lower, compared to controls (p<0.01-0.001). For less active
      patients (<5900 MET-minutes/week) with the right eye examined, the odds ratio of
      cataract was by 7.00 (95% confidence interval 2.93-16.74, p<0.001) and for those
      with the left eye studied by 4.43 (95% confidence interval 1.97-9.98, p<0.001)
      times higher, compared to physically active (>5900 MET-minutes/week) patients.
      Physical activity was inversely correlated (r=-0.452, p<0.05) with the lens
      opacity in the cortex in physically active (>5900 MET-minutes/week) subjects with
      cataract who underwent the examination of the left eye. CONCLUSION: The intensity
      of lens opacity and cataract are statistically significantly related to physical
      activity.

PMID- 17028473
TI  - [The impact of subclinical vertebral fractures on health-related quality of life
      in women with osteoporosis].
AB  - The aim of the study was to evaluate the impact of subclinical vertebral
      fractures on health-related quality of life in women with postmenopausal
      osteoporosis. A disease-specific instrument, Quality of Life Questionnaire of the
      European Foundation for Osteoporosis (QUALEFFO-41) questionnaire, developed to
      measure quality of life in patients with osteoporosis, was used. A total of 120
      postmenopausal women who came for consultation were examined. Subclinical
      vertebral fractures were identified by standardized lateral radiographs. Patients
      were divided into three study groups according to bone mineral density and
      incident fracture status: group 1 (control group)--40 women without osteoporosis,
      group 2--40 women with osteoporosis, but without vertebral fracture, and group 3-
      40 women with subclinical osteoporotic vertebral fracture. The last group was
      divided into two subgroups: with one fracture and with multiple vertebral
      fractures. The mean total score of the QUALEFFO-41 for the control group was
      34.12 (95% CI 30.27-37.96), for the group with osteoporosis, but without
      vertebral fracture--36.51 (95% CI 33.56-39.45), and for the group with non
      clinical osteoporotic vertebral fracture--35.69 (95% CI 32.08-39.29). There were
      statistically significant differences in domains A (pain) and E (social function)
      between women with one non-clinical vertebral fracture and control group. Our
      results showed no statistically significant differences in health-related quality
      of life, assessed QUALEFFO-41, between women with subclinical vertebral fractures
      and control group. Women with one subclinical vertebral fracture showed
      statistically significant worse results in pain, social function, and general
      health perception domains. Significantly greater changes in body appearance were
      noted among women with multiple subclinical vertebral fractures.

PMID- 17028474
TI  - [The results of thyroid ultrasound examination in randomly selected
      schoolchildren].
AB  - Iodine deficiency is an actual problem of public health and mostly manifests as
      enlargement of the thyroid (goiter). OBJECTIVE: The aim of the study was to
      determine the prevalence of goiter using different evaluation criteria and to
      establish the relationship between changes in thyroid volume and dimensions of
      the body. MATERIAL AND METHODS: Thyroid palpation and ultrasound examination were
      performed in 310 (7-11-year-old) randomly selected schoolchildren from two
      Lithuanian nearby small towns (Birzai and Rokiskis) in the district with lowest
      urinary iodine excretion (5.4 and 4.5 microg/dl). The size of thyroid gland was
      determined by inspection and palpation using the World Health Organization
      criteria. All children were examined ultrasonographically; thyroid volume was
      assessed by two criteria: F. Delange (1997) and M. B. Zimmermann (2004). RESULTS:
      There were no differences in means and medians of age and all body parameters
      (height, weight, body surface area, body mass index) in boys and girls of the
      same age. Higher means and medians of the body surface area in all age groups
      were found in Birzai as compared to Rokiskis (p<0.05). Comparing body mass index
      of all investigated schoolchildren with upper limits (97th percentile) of body
      mass index of normal British children, no statistically significant difference in
      the prevalence of obesity between towns was observed (1.9% - in Rokiskis, 5.0% -
      in Birzai; p>0.05). Grouping the children according to age revealed a higher
      prevalence of goiter in Birzai as compared to Rokiskis (88% vs. 63%,
      respectively, according to M. B. Zimmermann and 25% vs. 10%, respectively,
      according to F. Delange; p<0.05). There was no significant difference in the
      prevalence of goiter between the towns when children were grouped by body surface
      area. In all groups by age and body surface area, the mean thyroid volume
      exceeded 97th percentile by M. B. Zimmerman and did not exceed by F. Delange.
      CONCLUSIONS: The prevalence of goiter, assessing the thyroid volume in 7-11-year
      old children by the different criteria, is significantly different. We recommend
      using the criteria based on body surface area in order to evaluate the
      constitutional characteristics of individual child's development.

PMID- 17028475
TI  - Association between environment and psycho-emotional stress experienced at sea by
      Lithuanian and Latvian seamen.
AB  - This is the first scientific research in Lithuania and Latvia that involves a
      national cross-sectional study of the seamen of two different countries-
      Lithuania and Latvia--including the evaluation and comparison of seamen's working
      environment, lifestyle, health, the prevalence of health-damaging risk factors,
      as well as the causative relationships between the objective and subjective
      health evaluation and psycho-emotional stress experienced at sea. The aim of the
      study was to investigate the frequency and predictors of the psycho-emotional
      stress experienced at sea by Lithuanian and Latvian seamen. Beside the common
      statistical methods, the logistic stepwise regression analysis was used in order
      to find the risk factors of the self-rated stress and to correct the risk
      estimates for the confounding variables. Seamen of both countries indicated that
      they experienced psycho-emotional stress after, on the average, 2.7-2.8 months
      from the beginning of the voyage. More than one-half (57.5%) of Latvian seamen
      stated that they had experienced psycho-emotional stress, whereas the respective
      percentage of Lithuanian seamen was smaller (46.1%). The obtained findings showed
      that, having evaluated the influence of all the analyzed factors (industry
      specific, health and lifestyle, medical and demographic), there was no
      significant difference between the seamen of the two countries concerning the
      experience of psycho-emotional stress on the ship. The following main prognostic
      factors related to the occurrence of psycho-emotional stress on the ship were
      determined: higher or specialized secondary education level (p<0.001), age of 35
      44 or 45-54 years (p<0.01), 9-10 or 11-12 hours of work per day when being
      exposed to detrimental factors (p<0.01), the evaluation of one's health status as
      "average" (p<0.05), and evaluation of one's physical capacity as "quite good" or
      "average" (p<0.01). The occurrence of psycho-emotional stress was mostly
      influenced by work in the environment requiring increased visual strain (p<0.001)
      and vibration (p<0.05). We found that the following factors were associated with
      the occurrence of psycho-emotional stress on the ship: depression that occurred
      more frequently at sea than on shore (p<0.001), disturbed working and resting
      regimen due to time zone changes (p<0.001), and disturbed regular sexual life
      (p<0.001). Many of the unique aspects of seafaring are unchangeable. However, it
      possible to modify, supplement, or develop new strategies to reduce the impact
      these factors have on the health of individual seafarers.

PMID- 17028476
TI  - [An update on multiple insulin injection therapy in type 1 and 2 diabetes].
AB  - Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or
      =7.0% according to American Diabetes Association and < or =6.5% according to
      International Diabetes Federation) is the primary goal in treating diabetes,
      which lowers the risk for diabetes-related complications. Insulin therapy is
      essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is
      initiated when glycemic control is inadequate despite the combination of
      antihyperglycemic drugs. The type of insulin therapy is selected according to the
      patient's lifestyle and needs. Multiple insulin injection therapy and premixed
      insulin therapy are usually administered. In multiple insulin injection therapy,
      basal insulin is administered one or two times a day, and regular human insulin
      or rapid-acting insulin analog is administered with each meal. The duration of
      action of regular insulin is 6-8 hours; therefore, the risk for postprandial
      hypoglycemia is increased. The action of novel insulin analogs (rapid- and long
      acting) closely mimics physiological insulin secretion. Three rapid-acting
      insulin analogs are currently available: insulin lispro, insulin aspart, and
      insulin glulisine. Insulin glulisine is the most recently approved rapid-acting
      insulin analog. It is safe, flexible, and effective in achieving target
      postprandial glycemic control. Moreover, the pharmacokinetics of insulin
      glulisine does not depend on the amount of subcutaneous fat. Basal insulins
      include intermediate-acting human insulins (neutral protamine Hagedorn) and long
      acting insulin analogs (insulin glargine, insulin detemir). The latter are the
      optimal choice covering basal insulin requirement. Compared to neutral protamine
      Hagedorn insulin, long-acting insulin analogs have no pronounced concentration
      peak and reduce nocturnal hypoglycemia risk and weight gain.

PMID- 17028477
TI  - Optimizing hypertension control in patients with multiple cardiovascular risk
      factors.

PMID- 17028478
TI  - Managing hypertension: state of the science.
AB  - Hypertension management is both routine and a challenge. Updated guidelines
      emphasize the need to achieve increasingly stringent blood pressure goals to
      reduce cardiovascular morbidity and mortality; however, the blood pressure of
      many patients who have been diagnosed with hypertension is not well controlled.
      Treating prehypertension nonpharmacologically may preempt the progression to
      hypertension, whereas early and aggressive management of hypertension with
      antihypertensive agents reduces short- and long-term cardiovascular risk.
      Treatment decisions should follow current guidelines while evaluating recently
      published clinical studies. When choosing between agents from different
      therapeutic classes or combining agents, physicians should consider current and
      targeted blood pressure levels, the patient's demographic profile, the presence
      or absence of compelling cardiovascular and metabolic indications, other
      comorbidities, and concurrent medication(s).

PMID- 17028479
TI  - Managing multiple cardiovascular risk factors: state of the science.
AB  - Cardiovascular risk comprises genetic, lifestyle, and metabolic factors. Risk
      factors frequently occur simultaneously, compounding the risk for a
      cardiovascular event. The most commonly occurring metabolic clustering includes
      elevated blood pressure, dyslipidemia (high triglyceride levels and low levels of
      high-density lipoprotein cholesterol), and impaired glucose tolerance or type 2
      diabetes mellitus. Together with visceral obesity, this clustering of risk
      factors is known as the metabolic syndrome. Although the definition of the
      metabolic syndrome and its relevance in clinical practice are the subject of
      discussion, there is emerging consensus about the importance of treating all risk
      factors early and aggressively. Recent evidence suggests that new-onset diabetes
      mellitus and microalbuminuria are independent risk factors that should be
      considered when assessing composite cardiovascular risk. Treatment should be
      tailored to a patient's risk profile, with consideration of the varying effects
      that agents of different therapeutic classes have on cardiovascular and metabolic
      parameters.

PMID- 17028480
TI  - Incremental risk-factor reduction improves overall cardiovascular benefit: is it
      time to abandon the silos?

PMID- 17028483
TI  - Relation of left ventricular hypertrophy to regional cerebral blood flow: single
      photon emission computed tomography abnormalities in essential hypertension.
AB  - Several reports have shown that left ventricular hypertrophy (LVH) is an
      independent predictor of acute cerebrovascular events. The aim of the present
      study was to investigate the relationship between LVH and cerebral blood flow in
      middle-aged patients with essential hypertension. Forty never-treated
      hypertensive patients (24 men, 16 women, aged 50-60 years) without clinical
      evidence of target organ damage were studied. Regional cerebral blood flow was
      measured by means of single photon emission computed tomography of the brain.
      Twenty-nine patients showed echocardiographic criteria of LVH; 11 patients did
      not show this feature. No differences were found in regional cerebral blood flow
      ratio of all brain areas studied between hypertensives with or without LVH except
      for the striatum area. The regional cerebral blood flow ratio was significantly
      reduced in the striatum region of hypertensive patients with LVH, compared with
      patients without LVH (91.5+/-7.4 vs 98.1+/-8.3; P=.023). This relationship
      remained significant after adjusting for blood pressure. The authors conclude
      that the presence of LVH in middle-aged patients with essential hypertension is
      associated with a reduction of regional cerebral blood flow in the striatum area.

PMID- 17028482
TI  - A randomized, double-blind trial comparing the effects of amlodipine
      besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure.
AB  - Evidence suggests that renin-angiotensin-aldosterone system inhibition
      ameliorates endothelial dysfunction. The authors examined the effect of
      amlodipine besylate/benazepril HCl combination treatment compared with amlodipine
      besylate monotherapy in modulating endothelial dysfunction. This multicenter,
      double-blind, 12-week study randomized 70 hypertensive subjects with at least one
      other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl
      (5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5
      mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced
      significant median increases from baseline in percentage flow-mediated
      vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow
      mediated vasodilation (25% and 16%, respectively). These improvements were
      numerically larger with combination treatment, but between-group differences did
      not achieve statistical significance. Reductions in systolic and diastolic blood
      pressure were significantly greater (P=.0452/P=.0297) with combination treatment
      (-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive
      correlation between change in systolic blood pressure and change in percent of
      flow-mediated vasodilation was demonstrated only for combination treatment.

PMID- 17028484
TI  - Changing patterns of initial drug therapy for the treatment of hypertension in a
      Medicaid population, 2001-2005.
AB  - Thiazide diuretics have been recommended as one preferred choice for the initial
      treatment of hypertension. This study was undertaken to determine whether Maine
      physicians initiating monotherapy for newly diagnosed hypertensive patients from
      2001-2005 used this guideline. The Maine Medicaid database was searched for the
      drug classes used to initiate monotherapy for patients followed for at least 6
      months. A total of 5373 patients were included. In 2001, the use of beta-blockers
      was 23.5%, diuretics 17.5%, angiotensin-converting enzyme inhibitors 37.5%,
      calcium channel blockers 9.5%, angiotensin receptor blockers 3.8%, and others
      8.2%. By 2005, the use of beta-blockers was 27.8%, diuretics 25.5%, angiotensin
      converting enzyme inhibitors 30.9%, calcium channel blockers 6.4%, angiotensin
      receptor blockers 1.6%, and others 7.7%. There was an increase in the use of
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in
      diabetics but no other condition affected drug choice. Although there was an
      increase in the use of diuretics as initial therapy in 2003 and 2004, this
      decreased in 2005. The increase in initial diuretic use was not reflected in
      patterns of ongoing antihypertensive use from 1997 to 2005. There appears to have
      been limited impact from the guidelines on initial drug choice and even less so
      on ongoing drug therapy.

PMID- 17028485
TI  - Insulin resistance, diabetes, hypertension, and renin-angiotensin system
      inhibition: reducing risk for cardiovascular disease.
AB  - Insulin resistance, diabetes mellitus, and hypertension are associated with
      significant cardiovascular morbidity and mortality. Lifestyle modifications
      effectively decrease the risk of progression to diabetes in high-risk patients,
      but intensive interventions can be costly and difficult for patients to maintain.
      The addition of pharmacotherapy is often necessary to treat hyperglycemia and
      hypertension and lower the risk of cardiovascular complications. Clinical trial
      data suggest the use of insulin-sensitizing and antihyperglycemic agents to delay
      the progression to diabetes. Similarly, analysis of data from clinical trials of
      angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
      indicate that the use of these agents results in fewer cases of new-onset
      diabetes among patients with hypertension, when compared with other
      antihypertensive agents. Angiotensin II has direct and indirect effects on
      insulin and its signaling pathways, providing support for the biologic mechanism
      underlying the benefits of renin-angiotensin system inhibition in preventing
      diabetes and cardiovascular events. Clinical trials now under way will further
      evaluate the role of renin-angiotensin system inhibition in preventing diabetes
      and its microvascular and macrovascular complications.

PMID- 17028486
TI  - The ASCOT Trial--are beta-blockers still useful as antihypertensive medication?

PMID- 17028487
TI  - Prehypertension: an important preventive medicine concept--or marketing ploy?

PMID- 17028488
TI  - Drug interactions and drugs that affect blood pressure.
AB  - Many antihypertensive drugs have important interactions with drugs used for
      different purposes; when these are used concomitantly, adverse effects on blood
      pressure can result. Fortunately, in recent years, the drug development process
      has generally discouraged the approval and marketing of antihypertensive drugs
      with this problem, although some anomalies still exist (eg, telmisartan +
      digoxin). Physicians who work in emergency departments are more familiar with
      illicit or unregulated drugs that affect blood pressure; chief among these are
      cocaine and other opioids, and methylphenidate and its congeners. The most
      important prescription drugs that affect blood pressure are the nonsteroidal anti
      inflammatory drugs (including selective inhibitors of the second isoform of
      cyclooxygenase) and steroids. Phenylpropanolamines, some antidepressants, and
      sibutramine can often be avoided, as they raise blood pressure in a significant
      proportion of those who take them. Conversely, the hypertensive effects of
      calcineurin inhibitors and erythropoietin are most commonly overcome by
      increasing the intensity of antihypertensive drug treatment, since these drugs
      are essentially unavoidable in most patients who receive them.

PMID- 17028489
TI  - Managing chronic severe hypertension in pregnancy.

PMID- 17028490
TI  - Does consumption of high-caffeine energy drinks affect blood pressure?

PMID- 17028491
TI  - Obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome is caused by upper airway collapse during
      inspiration, causing intermittent hypoxemia, hypercapnia, acidosis, sympathetic
      nervous system activation, and arousal from sleep. Nighttime blood pressure is
      higher, but unexpectedly, daytime hypertension occurs. The prevalence of
      hypertension is very high and the incidence of hypertension increases as the
      number of apneic and hypopneic events per hour rises. Obesity is a major
      predisposing factor for the development of obstructive sleep apnea. Daytime
      sleepiness, snoring, and breathing pauses are important symptoms to elicit from
      the patient or sleep partner. Resistant hypertension is an important clue.
      Overnight polysomnography is required for diagnosis. Weight loss, avoidance of
      nocturnal sedatives, cessation of evening alcohol ingestion, and avoidance of the
      supine position during sleep are initial therapeutic actions in mild obstructive
      sleep apnea syndrome. Continuous positive airway pressure is the treatment of
      choice for patients unable to find relief from lifestyle changes. Blood pressure
      modestly improves with treatment.

PMID- 17028492
TI  - Empower women through education and access.

PMID- 17028493
TI  - Negative campaign not in patients' best interest.

PMID- 17028494
TI  - Breaking through obesity with gastric bypass surgery.

PMID- 17028495
TI  - Acne: intervene early.
AB  - "There is no single disease which causes more psychic trauma, more maladjustment
      between parents and children, more general insecurity and feelings of
      inferiority, and greater sums of psychic suffering than does acne vulgaris."

PMID- 17028497
TI  - Evidence-based practice and the nurse practitioner.

PMID- 17028498
TI  - Popular diets: what practitioners should know.

PMID- 17028499
TI  - Breast cancer therapy and treatment guidelines.

PMID- 17028500
TI  - Ibandronate (boniva) offers new options for osteoporosis.

PMID- 17028502
TI  - Thyroid disease associated with exposure to the Nevada nuclear weapons test site
      radiation: a reevaluation based on corrected dosimetry and examination data.
AB  - BACKGROUND: A study was begun in 1965 to 1966 to determine whether children
      exposed to radioactive iodine from nuclear weapons testing at the Nevada Test
      Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we
      reported that among those examined in 1985 to 1986 (Phase II) there was an
      association between radiation from the Nevada Test Site and thyroid neoplasms.
      METHODS: We reevaluated the relationship between exposure to Nevada Test Site
      fallout and thyroid disease using newly corrected dose estimates and disease
      outcomes from the Phase II study. A prospective cohort of school children 12 to
      18 years old living in Utah, Nevada, and Arizona was first examined for thyroid
      disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report,
      2497 subjects formed the basis for this analysis. Thyroid disease, including
      thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk
      ratios (RRs) with a dose-response expressed as excess risk ratio (ERR/Gy).
      RESULTS: The RR between thyroid radiation dose in the highest dose group and
      thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for
      thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence
      interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to
      estimate risk. CONCLUSIONS: Persons exposed to radioactive iodine as children
      have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30
      years after exposure.

PMID- 17028503
TI  - Sequential meta-analysis of past clinical trials to determine the use of a new
      trial.
AB  - BACKGROUND: Clinical trials can be stopped early based on interim analyses or
      sequential analyses. In principle, sequential analyses can also be used to decide
      whether enough evidence has been gathered in completed trials to make further
      trials unnecessary. We demonstrate such an application through a retrospective
      analysis of clinical trials comparing ventilation methods for the treatment of
      preterm newborns. METHODS: We identified 5 recent trials that compared high
      frequency ventilation with conventional mechanical ventilation in the treatment
      of preterm newborns. Death or chronic lung disease and chronic lung disease in
      survivors were the primary clinical outcomes of interest. We applied sequential
      meta-analyses to these 5 studies. RESULTS: After including the first study of the
      last 5 trials in a sequential meta-analysis, the boundary of "no clinically
      relevant effect" was crossed for both outcomes (death or chronic lung disease). A
      sensitivity analysis using a reduction in the size of assumed clinically relevant
      effect showed the same findings after 2 trials. CONCLUSIONS: Sequential meta
      analyses showed that a lack of clinically relevant effect had been established
      after the first of the 5 trials. If such an analysis had been conducted after the
      first or second of these clinical trials, it might have led to changes in the
      study design of subsequent trials or even to a reassessment of the need for
      further trials.

PMID- 17028504
TI  - Risks for skin and other cancers up to 25 years after burn injuries.
AB  - BACKGROUND: Malignant degeneration of chronic ulcers such as nonhealed burn
      wounds has been described in the literature, but this phenomenon has never been
      quantified in an epidemiologic study. We investigated the risks for skin and
      other cancers among patients with a prior burn. METHODS: We identified 16,903
      patients from the Danish Hospital Discharge Register who had been admitted to a
      hospital with a thermal or chemical burn during 1978 to 1993. The cohort was
      followed for cancer in the Danish Cancer Registry through 2002, and the cancer
      incidence in the cohort was compared with that in the general population of
      Denmark. RESULTS: Patients with burn had 139 skin cancers, with 189 expected,
      yielding a standardized incidence ratio of 0.7 (95% confidence interval = 0.6
      0.9). This reduced risk was due mainly to deficits of basal cell carcinoma and
      malignant melanoma, whereas the number of squamous cell carcinomas observed was
      close to expected. We saw no consistent increases in risk for skin cancer in the
      subgroups of patients with the most severe injuries or with the longest periods
      of follow up. CONCLUSIONS: The tendency to malignant degeneration of burn scars,
      described in previous reports of case series, did not result in an excess of
      squamous cell carcinoma of the skin or of any other type of skin cancer during up
      to 25 years' follow up of a large unselected cohort of patients hospitalized for
      burn injuries.

PMID- 17028505
TI  - Models for the relationship between ambient temperature and daily mortality.
AB  - BACKGROUND: Ambient temperature is an important determinant of daily mortality
      that is of interest both in its own right and as a confounder of other
      determinants investigated using time-series regressions, in particular, air
      pollution. The temperature-mortality relationship is often found to be
      substantially nonlinear and to persist (but change shape) with increasing lag. We
      review and extend models for such nonlinear multilag forms. DEVELOPMENT: Popular
      models for mortality by temperature at given lag include polynomial and natural
      cubic spline curves, and the simple but more easily interpreted linear thresholds
      model, comprising linear relationships for temperatures below and above
      thresholds and a flat middle section. Most published analyses that have allowed
      the relationship to persist over multiple lags have done so by assuming that
      spline or threshold models apply to mean temperature in several lag strata (e.g.,
      lags 0-1, 2-6, and 7-13). However, more flexible models are possible, and a
      modeling framework using products of basis functions ("cross-basis" functions)
      suggests a wide range, some used previously and some new. These allow for stepped
      or smooth changes in the model coefficients as lags increase. Applying a range of
      models to data from London suggest evidence for relationships up to at least 2
      weeks' lag, with smooth models fitting best but lag-stratified threshold models
      allowing the most direct interpretation. CONCLUSIONS: A wide range of multilag
      nonlinear temperature-mortality relationships can be modeled. More awareness of
      options should improve investigation of these relationships and help control for
      confounding by them.

PMID- 17028506
TI  - Prospective study of plasma folate, vitamin B12, and cognitive function and
      decline.
AB  - BACKGROUND: The relation between B vitamins and cognitive decline is
      controversial. In this study, we explored the association of plasma folate and
      vitamin B12 with cognitive function measured approximately 10 years later.
      METHODS: We determined plasma folate and vitamin B12 levels from blood samples
      collected in 1989 to 1990 and initially evaluated cognition in 1995 to 2001 among
      635 women, age 70+ years, from the Nurses' Health Study. In a subset of 391, 3
      repeated cognitive tests were completed for evaluation of cognitive decline over
      4 years; repeated testing is ongoing for the remaining women. Our primary outcome
      was a global composite score of 6 neuropsychologic tests administered by
      telephone. We used linear regression models to estimate multivariable-adjusted
      mean cognitive performance across quartiles of the vitamins and longitudinal
      models for cognitive decline. RESULTS: Higher vitamin levels were not associated
      with either initial cognitive performance or subsequent cognitive decline. Mean
      difference in initial global score for top versus bottom quartiles was 0.06
      standard units for folate (95% confidence interval [CI] = -0.10 to 0.22) and 0.15
      units for vitamin B12 (0.00 to 0.31). There were no dose-response trends for
      either nutrient. Women with high levels of both nutrients initially performed
      better than women low in both nutrients (global score, mean difference = 0.34;
      95% CI = 0.05 to 0.62); this association did not hold for subsequent cognitive
      decline. CONCLUSIONS: Combined B vitamin deficiency may be associated with
      impaired cognition, but in these healthy, well-nourished women, plasma folate and
      vitamin B12 were not related to cognitive function.

PMID- 17028507
TI  - Maternal use of selective serotonin reuptake inhibitors and risk of congenital
      malformations.
AB  - BACKGROUND: Human data on the teratogenicity of selective serotonin reuptake
      inhibitors (SSRIs) are limited. We examined the association between SSRI use
      during early pregnancy and the risk of congenital malformations in the offspring.
      METHODS: In a population-based cohort study from Denmark, we identified 1051
      women who filled prescriptions for SSRIs from 30 days before conception to the
      end of the first trimester; of those, 453 filled the prescription during the
      second or third pregnancy month. We included 150,780 women with no SSRI
      prescriptions as a reference cohort. Drug use data were extracted from
      prescription databases. Data on congenital malformations and potential
      confounders were extracted from hospital discharge registries and the National
      Birth Registry. RESULTS: The 150,780 women with no SSRI prescriptions gave birth
      to 5112 (3.4%) children with congenital malformations. The 1051 women with SSRI
      prescriptions any time during early pregnancy gave birth to 51 (4.9%) children
      with congenital malformations. The corresponding adjusted relative risk (aRRs)
      was 1.34 (95% confidence interval = 1.00-1.79). The 453 women with prescriptions
      during the second or third month of pregnancy gave birth to 31 (6.8%) children
      with congenital malformations. The corresponding aRR was 1.84 (1.25-2.71).
      CONCLUSIONS: We found an increased risk of congenital malformations after
      exposure to SSRIs in early pregnancy. It is unclear whether the effects were
      causal or due to factors related to the underlying disease. There was no evidence
      that the association was specific to particular malformations.

PMID- 17028509
TI  - Systemic immune response to Trichomonas vaginalis infection during pregnancy.
AB  - OBJECTIVE: The objective of this study was to characterize the systemic immune
      response in women with trichomoniasis in pregnancy as compared with uninfected
      women. STUDY DESIGN: A nested case control study was performed on 195 serum
      samples. Serum concentrations of cytokines, chemokines, and C-reactive protein
      (CRP) were compared between infected and uninfected women. Cytokines and
      chemokines were measured using a multiplex bead assay. The CRP concentrations
      were determined using a standard enzyme-linked immunosorbent assay method.
      RESULTS: The median serum concentration of granulocyte-macrophage colony
      stimulating factor (GM-CSF) was significantly higher in the trichomonas-infected
      group compared with the uninfected group (8.9 pg/mL vs. 5.7 pg/mL; P <0.001). The
      mean log-transformed CRP values were higher in the infected group compared with
      the uninfected group (1.66 vs. 1.27; P = 0.03). CONCLUSIONS: The results of this
      study suggest that trichomoniasis during pregnancy can lead to a systemic immune
      response in some women as exhibited by elevation in the serum concentrations of
      both GM-CSF and CRP.

PMID- 17028508
TI  - Safety and tolerability of methylphenidate in preschool children with ADHD.
AB  - OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3-
      to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD)
      during 1 year of treatment. METHOD: Exactly 183 children (3-5 years old) entered
      a treatment study of MPH, consisting of a 1-week open-label lead-in (n=183); a 5
      week placebo-controlled, double-blind phase (n=165); a 5-week double-blind,
      parallel phase (n=114); and 10 months of open-label maintenance (n=140 entered,
      95 completed). Mean total daily MPH doses rose from the titration trial best
      dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean total daily dose at the
      end of maintenance. Pulse, blood pressure, and the presence of treatment emergent
      adverse events (AEs), parent and teacher AE ratings, and vital signs were
      recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported
      moderate to severe AEs in all study phases after baseline. These included
      emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts,
      appetite decrease, and irritability. During titration, decreased appetite
      (chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=4.0,
      p<.05) occurred statistically more often on MPH than on placebo. During
      maintenance, trouble sleeping and appetite loss persisted and other MPH-related
      AEs decreased. There were transient, one-time pulse and blood pressure elevations
      in five children. Twenty-one children (11%) discontinued because of drug
      attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued
      treatment because of intolerable MPH AEs. Of the serious AEs reported, one
      occurred in baseline, two in lead-in, three in titration, one in parallel, and
      one in maintenance. Only one was possibly related to MPH.

PMID- 17028510
TI  - Pelvic examination findings and Chlamydia trachomatis infection in asymptomatic
      young women screened with a nucleic acid amplification test.
AB  - BACKGROUND: Nucleic acid amplification tests (NAATs) allow chlamydia screening in
      asymptomatic women who otherwise may not have pelvic examinations. How often
      these women have examination findings that may prompt empiric therapy is unclear.
      OBJECTIVE: The objective of this study was to assess the relationship of
      chlamydia with pelvic examination findings in asymptomatic women screened by
      NAAT. METHODS: The authors conducted a retrospective analysis of clinical data
      from 577 young asymptomatic women screened by chlamydial transcription-mediated
      amplification (TMA). RESULTS: TMA was positive in 68 (11.8%). The most common
      examination finding was vaginal discharge (5.9%) followed by cervical ectopy
      (3.6%), endocervical mucopus (2.3%) or easily induced bleeding (2.3%), and
      cervical motion (1.4%) or adnexal (0.7%) tenderness. On multivariate analysis,
      only easily induced bleeding or mucopus predicted chlamydia (adjusted odds ratio
      [AOR] = 4.7; P = 0.010 and AOR = 4.4; P = 0.015, respectively). CONCLUSIONS:
      Abnormal pelvic examination findings were infrequent in asymptomatic young women
      screened by a chlamydial NAAT. However, endocervical bleeding or mucopus, when
      present, predicted chlamydia.

PMID- 17028511
TI  - Sexual risk behavior of married men and women in Bangladesh associated with
      husbands' work migration and living apart.
AB  - OBJECTIVES: This study aimed to ascertain the prevalence of sexual risk behavior
      among married men and women who had, or had not, lived apart from their spouse as
      a result of the husbands' work migration. METHODS: A cross-sectional survey was
      conducted among a random sample of 1,175 married women and 703 married men in 2
      rural areas of Bangladesh. RESULTS: Extramarital sex was reported by 64.2% (95%
      confidence interval [CI] = 58.7-69.7) of 296 men and 8.6% (95% CI = 7.6-9.6) of
      779 women who had lived apart from their spouse, 2 to 3 times higher than the
      proportions among those who had not lived apart (P <0.05). The proportions of men
      who reported sex with a female sex worker (50.7%; 95% CI = 45.0-56.4) or with
      another male (5.4%; 95% CI = 2.8-8.0), while living away, were double the
      proportions reporting they had done so before living away or among men who had
      not lived away (P <0.05). Only 2 men had ever used had a condom during sex with
      another male, and less than one third of men had used a condom during sex with a
      sex worker or during marital sex. CONCLUSIONS: The sexual risk behavior of
      married men living away from home may put themselves and their wives at risk for
      HIV infection and other sexually transmitted diseases.

PMID- 17028512
TI  - [Better management of patients with difficult asthma].

PMID- 17028513
TI  - [Difficult asthma].
AB  - Difficult asthma is a major issue in pulmonary medicine today because of its cost
      for patients and society. Difficult asthma is asthma that remains uncontrolled
      despite optimal specialist management. The validity of the diagnosis must be
      reconsidered in these cases: associated or differential diagnoses may be involved
      in the lack of control, and it is always necessary to assess the patient's
      treatment adhesion. Sufficient time--at least a year--must be taken to get to
      know the patient and to meet the objectives set. The standard asthma therapies
      should be tested objectively. Severe asthma is the reality of difficult asthma
      that endures despite a reaffirmed diagnosis, optimal compliance and controlled
      comorbidities. Better knowledge is needed of the pathophysiology of these
      patients' asthma. Improved knowledge of these phenotypes will make it possible to
      develop innovative treatments. They will need to be validated in clinical
      research for subsequent use that is wider but more rational because targeted at
      phenotypes likely to benefit from them.

PMID- 17028515
TI  - [Air pollution and cardiovascular and cerebrovascular disease: Epidemiologic
      data].
AB  - Recent convergent data suggest that air pollution affects the risk of acute
      atherothrombotic events including both myocardial infarction and ischemic stroke.
      The principal epidemiologic studies begun in the 1990s first examined the
      respiratory effects of atmospheric pollution and then focused on how pollution
      peaks affected cardiovascular risk. These studies used data from large
      metropolitan areas in North America and Asia as well as several large European
      cities to demonstrate the clear existence of a relation between air pollution and
      cardio- and cerebrovascular mortality. They also observed an increase in hospital
      admissions for myocardial infarctions and cerebrovascular accidents on days with
      high air pollution levels. The pollutants involved have not yet been clearly
      designated, but it appears that fine suspended particulate matter (PM2.5) and
      gaseous pollutants such as ozone appear to contribute strongly to these harmful
      effects. A complete analysis of these data shows the need for a thorough
      evaluation of the cardio- and cerebrovascular risks associated with air
      pollution, especially in French metropolitan areas. Precise identification of
      those at high risk from specific pollutants is essential to improve targeting of
      prevention strategies.

PMID- 17028514
TI  - [Safety of selective serotonin reuptake inhibitor antidepressants in children and
      adolescents].
AB  - Some behavioral side effects of selective serotonin reuptake inhibitor (SSRI)
      antidepressants have been known for a long time. Since the introduction of these
      drugs in the 1990s, publications have regularly reported behavioral side effects
      in children and adolescents, including excitation, motor restlessness, social
      disinhibition, and above all self-injurious ideation and behavior. Clinical
      trials provide only limited data. Although these data suggest that some self
      injurious and suicidal behavior may indeed occur in children and adolescents
      receiving SSRIs, they are too disparate to specify the frequency of these acts.
      Clinical trials provide useful data about drug efficacy, but their methodology is
      inappropriate for determining the frequency of such side effects. SSRI and
      suicidality: the data are difficult to read. Although some epidemiologic data
      suggest that SSRIs may increase the risk of occurrence of self-injurious and
      suicidal behavior in children and adolescents, other epidemiologic data show that
      the rate of suicide mortality in children and adolescents has decreased since the
      introduction of SSRIs. No known mechanism explains how SSRIs might increase the
      risk of these behavioral side effects. It is clear, however, that these effects
      are not particular to children and adolescents but may also be observed among
      adults. SSRIs must be used rationally and carefully in children and adolescents.
      They should not be administered routinely in youth with obsessive-compulsive or
      depressive disorders. Their use should be reserved for severe disorders or when
      psychotherapy alone has been shown to be inadequate, and when they are used,
      efficacy and side effects must be monitored carefully and frequently.

PMID- 17028516
TI  - [Osteoporosis priority: Reduce the number of fractures].

PMID- 17028518
TI  - [Diagnosing osteoporosis: Laboratory tests].
AB  - Malignant or metabolic causes of low bone mineral density must be sought after
      either a fragility fracture or the discovery of low bone density measurements.
      Laboratory tests for calcium and phosphate metabolism are normal in osteoporosis.
      Vitamin D deficiency is frequent and requires supplementation. Markers of bone
      remodeling can be useful in cases where the treatment decision is difficult.

PMID- 17028517
TI  - [Drug treatment of postmenopausal osteoporosis. What's New in 2006].

PMID- 17028519
TI  - [Osteoporosis: Optimizing treatment strategy].
AB  - Selection of patients for treatment is based on the assessment of their absolute
      fracture risk over 10 years. Assessment of fracture risk includes not only DXA
      measurement and age, the two principal risk factors, but also other clinical risk
      factors. The main goal of postmenopausal osteoporosis treatment is to reduce the
      risk of fragility fractures. Choice of treatment is based on drug properties,
      demonstrated in clinical trials, and patients' specific fracture risks. The
      minimum duration of treatment is 4-5 years, after which individual fracture risk
      must be reevaluated. Combinations of available drugs are not recommended for
      treatment of postmenopausal osteoporosis.

PMID- 17028520
TI  - [Osteoporosis in the elderly].
AB  - Osteoporosis is a frequent disease among the elderly and has major consequences
      in terms of mortality, morbidity and cost. Guidelines for diagnostic procedures
      are often difficult to apply in frail, elderly patients with multiple
      comorbidities. Bisphosphonates are the reference treatment for the elderly,
      combined with vitamin D and calcium supplementation. Vitamin D deficiency must
      also be treated to prevent falls and fractures. Strontium ranelate is a promising
      treatment in this population. Fall prevention is a major part of osteoporosis
      management. The potential benefit of hip protectors is questionable, even in
      institutionalized patients.

PMID- 17028521
TI  - [Hormone replacement therapy in the management of postmenopausal osteoporosis and
      prevention of fracture risk].
AB  - The consequences to the bone of estrogen deficiency are early and irreversible.
      Effective prevention of postmenopausal osteoporosis at the individual level
      requires early screening of women at risk of fractures and their early treatment.
      Hormone treatment prevents bone loss and has been proven effective in preventing
      fractures, even in situations of low risk. The benefit/risk ratio of hormone
      treatment can be optimized by the choice of the 'right moment' and the 'right
      treatment'. HRT, administered early and for a limited period, must be integrated
      into a strategy of long-term osteoporosis prevention that includes using the
      (drug and nondrug) means most appropriate to the patient's age and clinical
      condition and choosing the 'right moment' and 'right treatment.'

PMID- 17028522
TI  - [Follow-up of osteoporosis treatment].
AB  - There is no linear relation between changes in bone mineral density (BMD) and
      reduction in fracture risk with antiresorptive agents. Interpretation of BMD
      changes at the individual level requires calculating the smallest significant
      change at each measurement center. BMD measurement is essential before
      administration of antiresorptive or anabolic agents for prevention or treatment
      of postmenopausal osteoporosis. Biochemical markers of bone turnover can be
      monitored after 6 months of treatment. Their interpretation requires careful
      assessment of their intraindividual variability.

PMID- 17028523
TI  - [Management of corticosteroid-induced osteoporosis].
AB  - Corticosteroid-induced osteoporosis is common but too often unrecognized, and its
      management remains insufficient. Bone loss is variable from one patient to
      another and thus difficult to predict, but all treated patients must be
      considered at risk. There are tools to assess absolute fracture risk in this case
      as there are for menopause-associated osteoporosis, and they may help guide the
      clinician in decision-making. Recent guidelines help the physician to define
      indications for bone mineral density testing and for therapeutic management.
      Bisphosphonates are currently the first-line treatment for patients with
      fractures or elevated fracture risk during corticosteroid treatment.

PMID- 17028525
TI  - [Meningeal carcinomatosis].

PMID- 17028526
TI  - [The future of peer review of medical articles].

PMID- 17028524
TI  - [Non-corticosteroid drug-induced metabolic bone disease].
AB  - After osteoporotic fracture or low bone mineral density measurements, it is
      necessary to look for secondary causes of osteoporosis, such as drugs.
      Corticosteroids are the most common cause of drug-induced metabolic bone disease.
      Other drugs responsible for bone disease include: aromatase inhibitors, GnRH
      agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses.
      Confirmation is required of data about neuroleptics and antivitamin K.

PMID- 17028527
TI  - [Influenza: A nosocomial infection].

PMID- 17028528
TI  - [Legal insecurity of doctor-patient confidentiality].

PMID- 17028530
TI  - [Medical guidelines and medical practices: The example of lipid lowering
      therapy].
AB  - INTRODUCTION: The SPOT epidemiologic survey assessed the results of long-term
      cholesterol-lowering therapy in France and the reasons why patients do or do not
      meet their therapeutic objectives. OBJECTIVE: To assess the guidelines on which
      doctors base their practices for cholesterol-lowering therapy and make
      suggestions to improve the match between recommendations and practices. METHODS:
      LDL cholesterol was measured in 2479 French outpatients in 2003 and classified
      according to whether it met therapeutic objectives of 3 different scales: the
      official French (AFSSAPS) recommendations issued in 2000, the physician's opinion
      of the ideal level for the patient, and the physician's goal level for the
      patient. Agreement between these 3 criteria was analyzed. RESULTS: French doctors
      used guidelines stricter than the official recommendations to assess the
      achievement of lipid-lowering objectives. DISCUSSION: Physicians rely more on
      American than French guidelines. They also considered the patient's history and
      clinical condition in setting individual goals.

PMID- 17028529
TI  - [Nosocomial influenza outbreak in a geriatrics department: Effectiveness of
      preventive measures].
AB  - OBJECTIVE: To describe a nosocomial influenza outbreak and the pharmacologic and
      nonpharmacologic control measures implemented in a hospital ward with beds for
      acute geriatric care and rehabilitation care. METHODS: Descriptive survey
      conducted in the geriatrics department of a university hospital. An influenza
      outbreak occurred in February 2005 in 2 of the department's 3 separate units. The
      study concerned all patients in the 2 affected units (A and B) present during the
      outbreak, as well as all department staff. Once cases of influenza were
      confirmed, elderly patients in contact with influenza patients received
      chemoprophylaxis with oseltamivir when it became available. RESULTS: Thirty-eight
      (76%) patients and 62 (38%) staff members had been vaccinated. The time from the
      initial symptoms of the first case until implementation of control measures was 7
      days in unit A but only 1 day in unit B, -and chemoprophylaxis of contact
      patients began in 9 days and 24 hours respectively. The attack rate was 38% in
      the 38 vaccinated patients and 29% in the 14 unvaccinated patients (NS). All
      cases met the definition of nosocomial infection. No deaths imputable to
      influenza occurred during the outbreak. The implementation of the
      nonpharmacologic measures aimed at preventing spread of the outbreak presented no
      particular difficulty, except for compliance with geographic isolation of some
      patients with dementia and influenza. The difference between the attack rates for
      the two sectors (48% for unit A and 28% for unit B) suggests that the preventive
      measures were effective. Tolerance to chemoprophylaxis with oseltamivir was good.
      CONCLUSION: This study confirmed that influenza can affect elderly hospital
      patients, even those in whom the vaccination rate is high, and that rapid
      detection of the outbreak and immediate implementation of pharmacologic and
      nonpharmacologic preventive measures can limit its spread.

PMID- 17028531
TI  - [Health behavior of healthcare personnel: The European Presst-Next Study].
AB  - OBJECTIVES: The objective of the NEXT (Nurses' Early Exit) study was to identify
      the organizational and health factors in the 10 participating countries
      associated with job satisfaction of nurses and nurses' aides or with their desire
      to change occupation or stop working prematurely. METHODS: Questions about health
      were somewhat more detailed in the French version of the questionnaire and
      allowed us to determine health behaviors of this representative sample of French
      caregivers (PRESST: Promotion of Health and Job Satisfaction of European
      Healthcare Workers [www.next-study.net; www.presst-next.fr]). RESULTS: Of the
      6980 (796 men and 6184 women) nurses and nurses' aides studied in late 2002 and
      early 2003, 32.6% reported that they smoked at least occasionally and 24.3%
      regularly. Only 24.4% of the staff in our sample exercised at least weekly.
      Overweight was observed in 27,6% of the sample, mostly women (42% of men and
      24.7% of women), and obesity affected 6,4% of men and 7% of women. Overweight was
      slightly less frequent than among the general adult population of France, 39.8%
      according to the CREDES SPS survey in 2002, but these healthcare workers were
      younger. On the whole, burnout was higher among French caregivers than among
      those from other European nations in the Next study. CONCLUSION: This study
      demonstrates the need to conduct and assess interventions for the dual purpose of
      (1) reducing the morbidity and mortality associated with the conditions most
      sensitive to these risk factors in healthcare personnel and (2) improving their
      knowledge, motivations and credibility in providing health education to patients.

PMID- 17028532
TI  - [Smoking cessation counseling center in a French hospital: Effectiveness at one
      year and predictors of outcome].
AB  - OBJECTIVE: To assess the effectiveness at 1 year of a hospital clinic providing
      individual management of persons seeking to stop smoking and the factors
      predictive of failure. METHODS: This prospective descriptive study included
      smokers seeking assistance at this hospital clinic over a 1-year period. This
      analysis excludes persons with schizophrenia and those who came only to a first
      consultation. Treatment methods were those recommended by the 1998 consensus
      conference: nicotine substitutes or slow-release bupropion, depending on the
      level of nicotine dependence, cognitive-behavioral therapy appropriate for
      smoking in all cases, and the prescription before cessation of a selective
      serotonin re-uptake inhibitor (SSRI) for patients with anxiety or depressive
      disorders. Assessment was based on patients' self-report at 3 months, 6 months
      and 1 year. RESULTS: Of 99 smokers who came for at least one consultation, 38
      were excluded and 61 were considered in the analysis. At one year, 18 patients
      (29.5%) were still not smoking. Of the 43 patients who resumed smoking, 27 (63%)
      did so during the first three months after cessation. According to the
      multivariate analysis, only female sex (p = 0.0173) and early end to follow-up (p
      = 0.0023) were significantly associated with the risk of relapse at 1 year.
      CONCLUSION: The study confirmed the usefulness of specialized medical support
      over a one-year period and highlighted the difficulties of smoking cessation for
      women, who appear to need a new not yet invented approach. The other standard
      factors predictive of failure were not observed, possibly because of either the
      broad prescription of SSRIs in cases of anxiety- or depression-related
      comorbidity or the statistical limitations associated with the population size.

PMID- 17028533
TI  - [Use and misuse of intravenous drug administration in a department of internal
      medicine].
AB  - AIM: Numerous intravenously-administered medications are also available in
      equally effective oral forms. To assess the number of avoidable intravenous
      infusions, we retrospectively analyzed consecutive infusions prescribed in a
      department of internal medicine. METHODS: Between November and December 2004, we
      analyzed all patients who received at least one intravenous drug during
      hospitalization. Intravenous administration was considered unavoidable when
      prescribed for no more than 2 days in a patient unstable at admission, when oral
      administration or feeding was impossible, or when the drug was not available in
      oral form. RESULTS: During the study period 133 patients were admitted to the
      department. In all, 65 infusions were prescribed, 30% of which lasted more than 2
      days for no medical reason. Four intravenous antibiotics were prescribed in
      patients when their antibiotic susceptibility tests indicated that another oral
      antibiotic could easily be given. Infusions for 16 other patients continued
      longer than 48 hours, although the oral route was not contraindicated in these
      patients and the medication was available in oral form. CONCLUSION: Systematic
      analysis of the daily prescriptions may be helpful in preventing or shortening
      use of intravenous medications and thereby decreasing iatrogenic infections and
      injuries, length of hospitalization, and costs.

PMID- 17028534
TI  - [Consultations with infectious disease specialists for patients in a teaching
      hospital: Adherence in 174 cases].
AB  - OBJECTIVES: In a teaching hospital where infectious disease specialists were
      routinely consulted for infections in patients in other departments, we sought to
      assess adherence to the specialists' recommendations, identify the factors
      influencing adherence, and measure the proportion of nosocomial infections among
      these consultations. METHODS: We collected data from intrahospital consultations
      with infectious disease specialists over a 4-week period. Afterwards (48 hours
      later), a physician and pharmacist collected all prescriptions for anti
      infectious agents (dose, drug, combinations) and other orders (laboratory tests,
      radiology examination, isolation) for each patient. RESULTS: There were 174
      infectious disease consultations requested for 143 inpatients during the study
      period. Anti-infectious agents were prescribed for 52.4% of patients, modified
      for 22.4%, and stopped for 9.1%; 16.1% neither had nor required such treatment.
      The rate of adherence to the specialists' recommendations was 84.6% for anti
      infectious prescriptions and 77.4% for other orders. The factors associated with
      adherence were a bedside consultation (p = 0.04) and a recommendation to stop
      rather than modify anti-infectious treatment (p = 0.02). Roughly 40% of the
      patients (n = 57) had a nosocomial infection, most often during hospitalization
      for surgery (53.1% versus 29.1%, p < 0.01). Consultations were requested for 20%
      of the nosocomial infections observed at Grenoble University Hospital (based on
      annual prevalence in 2005). CONCLUSIONS: The specialist's presence at the
      patient's bedside has an impact on staff adherence to recommendations. These
      specialists play a vital role in managing nosocomial infections, which account
      for more than a third of these intrahospital' consultations.

PMID- 17028535
TI  - [Changes in prenatal ultrasound practices after the Perruche decision and Law no.
      2002-303 dated 4 March 2002].
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of French law (court
      rulings in the Perruche decision and its progeny as well as the statute enacted
      on March 4, 2002 to reverse or moderate this jurisprudence) on physicians'
      prenatal diagnosis and fetal medicine practices. METHODS: We sent questionnaires
      to 186 physician-ultrasonographers in two French districts, inquiring about
      changes in their daily practice and their provision of information to and
      communication with the future parents, as well as their opinions about the future
      of their specialization. RESULTS: We received 54 responses (29%): 40% of
      respondents found it more difficult to tell patients about fetal anomalies.
      Written and oral information, medical reports and explanations about the
      limitations of ultrasound have improved substantially in content for 64% and are
      better used for 42%. Some clinicians (24.1%) report that they take the future
      parents' emotions into account more often. Some try to be more distant (13%) or
      more neutral (9.3%). More than half (51.9%) request the opinion of a center for
      prenatal diagnosis and fetal medicine more often and 20.4% request karyotyping
      more often. In all, 7.4% believe that their counseling now leads more often
      towards abortions. CONCLUSION: Although practitioners had an extremely negative
      perception of the case law and some were also unhappy with the new statute, these
      did lead to the reorganization and formalization of their practices. We can see
      that judicial decisions taken in a specific, individual situation can change
      collective practices and influence--or even overturn--public health strategies.
      The respondents' intention to take parents' emotions into account suggests they
      will find a common language to communicate with them. It is nonetheless necessary
      to organize a nationwide debate about the objectives of fetal ultrasound.

PMID- 17028537
TI  - [Gallbladder volvulus: Two cases].
AB  - INTRODUCTION: Gallbladder volvulus remains a relatively rare disorder.
      OBSERVATION: We report two cases, both in men older than 80 years and both
      diagnosed during surgery. Both patients presented signs of peritonitis (one
      generalized and the other localized) and severe sepsis. DISCUSSION: We review the
      literature about gallbladder volvulus to analyze its incidence, etiology, and
      clinical, radiologic and therapeutic characteristics.

PMID- 17028536
TI  - [Adult idiopathic neutrophilic eccrine hidradenitis treated with colchicine].
AB  - INTRODUCTION: Neutrophilic eccrine hidradenitis (NEH) is a rare disease belonging
      to the group of neutrophilic dermatoses. It has a characteristic histopathologic
      pattern, with necrosis of the eccrine glands and a local neutrophilic infiltrate.
      It occurs mostly in patients receiving chemotherapy for acute myeloblastic
      leukemia or, less frequently, another malignancy. Its occurrence in healthy
      patients is rare. CASE REPORT: We report the case of a 56-year-old woman with no
      remarkable medical history who developed an erythematous papular facial eruption.
      Skin biopsy showed typical features of neutrophilic eccrine hidradenitis
      including neutrophilic infiltrate. No cause was found. The patient was
      successfully treated with colchicine. DISCUSSION: This case is particular because
      NEH was not associated with malignant hematologic disease, solid cancer,
      chemotherapy, fever or any other disease, after a follow-up of 22 months. Such
      idiopathic NEH has been reported only rarely in adults. The second particularity
      is the length of the eruption, which required colchicine treatment. Clinical
      improvement occurred within 1 month. Because hematologic malignancies can in some
      cases be preceded by neutrophilic dermatitis, clinical follow-up is recommended
      in adults.

PMID- 17028538
TI  - [Magnetic resonance imaging of endomyocardial fibrosis].

PMID- 17028539
TI  - [The return of psychosurgery].

PMID- 17028540
TI  - [New surgical techniques for brain tumors].
AB  - During the past years, the development of new technologies and techniques has
      been applied to brain tumor surgery, leading to decreased surgical morbidity and
      increased efficiency. These techniques can be used to reduce the invasiveness of
      the surgical approach (endoscopy, neuronavigation, robotics), to improve guidance
      (stereotaxy, neuronavigation), to better identify the tumor limits
      (neuronavigation, metabolic imaging, intra-operative MRI) or the functional areas
      (functional imaging, electrophysiological functional mapping) to optimize
      resection and to respect eloquent areas. This article reviews these techniques,
      focusing on their respective principles, practical utility, impact and limits.

PMID- 17028541
TI  - [How do the temporal lobes communicate in medial temporal lobe seizures?].
AB  - INTRODUCTION: Spatial and temporal patterns of the spread of partial epileptic
      seizures depend on the site from which they originate. Characterising seizure
      propagation patterns may help to better define the seizure focus. In medial
      temporal lobe epilepsies, seizure propagation to the contralateral temporal lobe
      is especially studied. STATE OF THE ART: Intracranial EEG records permit more
      precise definition of patterns of contralateral propagation in medial temporal
      lobe epilepsies. Several pathways have been implicated, sometimes differently in
      distinct studies, in propagation to the contralateral temporal lobe: the three
      commissures (the corpus callosum, the ventral hippocampal commissure and the
      anterior commissure, which link the temporal lobes) and an indirect circuit via
      the frontal lobes. Delays measured for contralateral propagation of a seizure of
      temporo-limbic origin vary significantly around a mean value of about 30 seconds.
      This slow spread may depend in part on the relatively small size of human
      commissural projections from the amygdalo-hippocampal formation, which largely
      originate in the presubiculum. However, a larger commissural projection pathway
      originates in the paralimbic medial temporal lobe and electrical stimulation of
      the anterior perirhinal cortex can induce contralateral epileptic discharges with
      delays as short as 100 ms (Adam et al., 2004). Thus, seizure activity emerging
      from anterior paralimbic regions can propagate rapidly to the contralateral
      medial temporal lobe via the anterior commissure. PERSPECTIVES: While the
      propagation of medial temporal lobe seizures is still debated, further studies
      are merited since the extent and speed of spread governs the electro-clinical
      semiology of seizures and our ability to identify their initiation site.
      CONCLUSIONS: We review anatomical (Demeter et al., 1990) and neurophysiological
      (Wilson et al., 1990) data for a dual inter-temporal propagation of medial
      temporal lobe seizures at different speeds and via different pathways.

PMID- 17028542
TI  - [Unverricht-Lundborg disease (PME1)].
AB  - Unverricht-Lundborg disease (ULD) is the purest and least severe type of
      progressive myoclonus epilepsy (PME), and is not associated with progressive
      cognitive deficit. Symptoms stabilize in adulthood, with a varying degree of
      permanent, often severe handicap that is mostly due to myoclonus. The disorder
      follows an autosomal recessive transmission pattern, with onset between 8 and 15
      years years of age of generalized tonic-clonic or clonic-tonic-clonic seizures,
      action myoclonus (massive or segmental), photosensitivity, and often ataxia.
      Prevalence varies, it is highest in certain isolates (Finland, La Reunion Island)
      and in region with higher levels of inbreeding (Maghreb). ULD is due to a deficit
      in cystatin B (stefin B), but the mechanisms leading to the clinical symptoms are
      not well understood. The causative gene, PME1, was identified in 1991 and
      localized to chromosome 21q22.3. The mutations are mainly expansions of the
      CCCCGCCCCGCG dodecamer, but less common point mutations were also found. A
      variant has been recently reported in a Palestinian family, with localization on
      chromosome 12. The diagnosis of ULD is made on the basis of family history, age
      at onset, geographical and ethnic context, and on the typical features of
      myoclonus and epilepsy, in the absence of cognitive and sensory deficits.
      Neurophysiological evaluation yields interesting, but unspecific results. There
      are no biological or pathological markers for ULD. Molecular analysis confirms
      the diagnosis in most patients. Genetic testing for heterozygotes and even
      prenatal diagnosis are possible, although seldom performed, if the mutation has
      been identified. In spite of intensive research, ULD has yet to reveal all of its
      secrets. It remains a quasi "idiopathic" type of PME, with limited progression.
      Clinicians and patients are still waiting for an etiologically oriented
      treatment, which should, ideally, be admnistered early in the course of the
      disease, if possible before the onset of invalidating symptoms.

PMID- 17028543
TI  - [CADASIL with minimal symptoms after 60 years].
AB  - INTRODUCTION: CADASIL is a hereditary cerebral arteriopathy leading to
      progressive disability and dementia usually observed at 60 years. OBSERVATION: We
      report four patients aged>60 years with typical Notch3 mutations leading to
      CADASIL who did not have dementia or disability. Three of them presented with
      only transient neurological manifestations. MRI results showed extensive
      hyperintense signals in the white-matter on T2-weighted images contrasting with
      very few lacunar infarcts. CONCLUSION: These observations suggest that silent or
      symptomatic infarcts, which were rare in the present cases may be responsible for
      the clinical severity in this disorder.

PMID- 17028544
TI  - [Stiff man syndrome: clinical forms, treatment and clinical course].
AB  - INTRODUCTION: Stiff-Man syndrome (SMS) is a rare neurological disease first
      described fifty years ago. There are several clinical forms, which are frequently
      misdiagnosed. The aim of this study is to review three of the main clinical
      forms. MATERIAL AND METHODS: Case reports concerning three women suffering from
      different forms of SMS are presented, giving the main clinical features, their
      associations with other diseases, and the biological and electrophysiological
      findings. RESULTS: The first patient presented a symmetric axial muscle rigidity,
      painful spasms and contractions of the trunk and limbs associated with anti-GAD
      antibodies. The common form of SMS was diagnosed and the patient was improved by
      intravenous immunoglobulin (IVIg). The second patient suffered from contractions
      and spasms localized to the lower limbs. In this patient, anti-GAD antibodies
      were absent. The Stiff-Leg syndrome was diagnosed and the patient was improved by
      intrathecal baclofen. The third patient presented rigidity of limb and trunk
      muscles associated with signs of encephalitis. In this patient, only anti
      amphiphysin antibodies were present. The progressive encephalomyelitis with
      rigidity was diagnosed and the patient was improved by IVIg associated with
      corticosteroid. CONCLUSION: Identifying patients with SMS makes it possible to
      propose appropriate medical management. There are several forms of the disease,
      and the severity of the evolution differs in each case. Treatment with GABA-ergic
      inhibitory drugs, IVIg and corticosteroid improve both the symptomatology and the
      quality of life of these patients.

PMID- 17028546
TI  - [Multiple gliomas: clinical studies and pathophysiological hypothesis].
AB  - INTRODUCTION: Although a rare entity, multiple gliomas must be recognized and
      distinguished from other causes of multiple brain lesions. METHODS: Clinical and
      radiological features of 33 multiple gliomas were reviewed, including 20
      synchronous cases and 13 metachronous cases. RESULTS: In 17 patients,
      radiological features were highly suggestive of spread from a primary site
      (multifocal gliomas). No apparent dissemination route was identified in the other
      cases which were presumed to be multicentric gliomas. For nine patients (27
      percent), a second neoplasia or cancer was found in first degree relatives
      suggesting a genetic predisposition. Overall median survival was 79 weeks (64
      weeks for glioblastomas). The age at onset was the main prognostic factor.
      CONCLUSION: Multiple gliomas represent a heterogeneous entity, probably
      corresponding to different mechanisms. In our group, survival was comparable to
      unique glioma.

PMID- 17028545
TI  - [Homocysteinemia and thrombophilic factors in unexplained decompression
      sickness].
AB  - INTRODUCTION: Decompression sickness with cerebral ischemic lesions occurs even
      in divers who have not committed any technical error. This study sought to
      determine whether an acquired or inborn thrombophilic factor might be involved.
      METHODS: 44 divers with ischemic medullar lesions (36 men, 8 women, mean age
      39.9+/-4.7 yr) were compared with 44 controls (34 men, 10 women, mean age 38.2+/
      5.1 yr). Coagulation screening included proteins S, C, and thrombin III and
      Factor VIII assays and circulating antibodies, Factor V Leiden, and mutation
      G20210A in Factor II gene research. Total plasma homocysteine (Hcy), an
      atherosclerosis factor (assayed by FPIA), folate and vitamin B12, (by
      microbiology), the cofactors of its metabolism, were assayed, and subjects were
      genotyped for mutation C677T on the MTHFR gene. RESULTS: Coagulation screening-
      protein C, protein S, or antithrombin III deficit or mutation G20210A--was
      negative in all divers. 3/44 divers were heterozygous for Factor V Leiden, 1/44
      had IgG antiphospholipid antibodies (9p.cent). While not found in controls, these
      percentages were not greater than those reported in the general population. 3/44
      divers had elevated Factor VIII levels, but repeat assays on Day 2 were much
      lower. 11/44 divers had a moderate increase in Hcy value (20p.cent): in 7 divers,
      Hcy values were>15 micromol/L, and in 4 others>12, vs. 2.3p.cent of the controls;
      2/11 had normal vitamin levels and 11 divers had folate or vitamin B12 deficiency
      or both, vs 2.3p.cent controls with a vitamin B12 deficit (percentage
      significantly different). 7/26 divers were homozygous for the C677T mutation,
      i.e. 27p.cent vs 12p.cent of 98 healthy controls (laboratory technicians).
      CONCLUSIONS: A high percentage of unexplained diving accident victims had
      moderate HHC, a folate or vitamin B12 deficiency or both, that are easy to
      detect, plus a genetic predisposition to HHC or to coagulation abnormality. Easy
      to-perform homocysteine, vitamin B12, and folate assays might prove helpful for
      primary prevention of diving accidents.

PMID- 17028547
TI  - [Study of episodic memory in multiple sclerosis using the California Verbal
      Learning Test: the data favour altered encoding].
AB  - INTRODUCTION: Alteration of episodic memory is one of the main cognitive deficits
      observed in MS patients. PATIENTS AND METHODS: We studied episodic memory in a
      group of 71 MS patients (37 RR, 34 SP) with the California Verbal Learning test
      (CVLT). Direct scores and calculated indices from CVLT performances were analyzed
      in comparison with controls. RESULTS: We observed a deficit of episodic memory in
      69 p.cent of patients. This deficit was related to an alteration of encoding and
      retrieval processes. Despite SP-MS patients performances were constantly lower
      than those of RR-MS patients no significant difference was observed between the
      two groups. Significant correlation between the disease duration and CVLT
      performances were observed for the whole group but not for RR- or SP-MS groups
      separately, indicating that duration is more important than the phase of the
      disease in the worsening of memory deficit.

PMID- 17028548
TI  - [Type I glutaric aciduria: an unrecognized cause of progressive dystonia].
AB  - INTRODUCTION: Glutaric acidemia type I is one of the least rare organic
      acidemias. The number of diagnosed causes is however still low because the
      presentation is variable and often confusing. The disease may sometimes have a
      slowly progressive course. Typically, it presents in infancy, mimicking acute
      encephalitis, leaving a previously healthy child severely handicapped with
      generalized dystonia, spastic quadriplegia or choreoathetosis. Cerebral MRI shows
      large CSF-containing spaces (sylvian fissures and anterior to the temporal lobes)
      and basal ganglia abnormal signal. CASE REPORT: An eight year-old boy had begun
      at 18 months with motor difficulties and abnormal posture of upper and lower left
      limbs. When examined, he had generalized dystonia more pronounced at the left
      side, severe dysarthria and tongue dystonia. IQ was normal. MRI showed high T2
      signal in basal ganglia and enlarged CSF containing spaces. Urinary organic acids
      chromatography confirmed glutaric acidemia type I. Two of his sisters deceased
      before the age of two years with a clinical picture of fever, seizures and
      hypotonia. Another sister had the same symptoms at the same age. She lived until
      10 year with severe quadriplegia. COMMENTS: Our observation shows variability of
      clinical picture and course of glutaric acidemia type I in the same kindred. We
      propose systematic organic acides chromatography in all children with acute or
      progressive dystonia with basal ganglia abnormalities on MRI. This seems an
      imperative attitude because appropriate diet could slow the progression of the
      illness.

PMID- 17028549
TI  - [Chemotherapy treatment for anti-Hu paraneoplastic syndrome without active
      malignancy].
AB  - INTRODUCTION: Anti-Hu associated paraneoplastic neurological syndromes are rare
      and characterized by poor prognosis. The research and treatment of a related
      cancer, a small-cell lung cancer most of the time, remains the best therapeutic
      strategy. CASE REPORT: We describe the clinical course of a paraneoplastic
      subacute sensory neuronopathy associated with anti-Hu antibodies in a male smoker
      treated by an early chemotherapy active against a small-cell lung cancer although
      no tumor could be found at repeated evaluations. In spite of this treatment, the
      neurological state deteriorated with the appearance of a cerebellar degeneration,
      and limbic encephalitis which resulted in a loss of autonomy. A small-cell lung
      cancer was found and treated 65 months after the onset of the neurological
      symptoms. The treatment of the underlying malignancy, when it can be found, is
      still considered as the optimal treatment for paraneoplastic neurological
      syndromes. Although no tumor could be found, we treated our patient with an
      empirical chemotherapy active against the most frequent malignancy associated to
      anti-Hu syndrome in a smoker man, without any improvement. CONCLUSION: Active and
      repeated research for a cancer related to an anti-Hu neurological syndrome and
      its treatment are undispensable. For our patient without any identified cancer
      empirical chemotherapy treatment was unable to stop neurological worsening. When
      no tumor can be identified by conventional imaging techniques, an early FDG-PET
      scan should be considered and then repeated if normal.

PMID- 17028550
TI  - [Peroneal nerve schwannoma presenting with a peroneal palsy].
AB  - Peroneal nerve injury in the lateral aspect of the knee is frequent, commonly
      dominated by traumatic or compressive etiologies. Tumors, generally synovial
      cysts, are exceptional causes. We report a case of a 70-year-old women referred
      for assessment of peroneal palsy syndrome found to be related to peroneal
      schwannoma in the lateral aspect of the knee. Schwannoma is the most frequent
      peripheral nerve benign tumor. It is commonly limited to cranial and upper limb
      nerves. Localization on the lower limbs (sciatic nerve) has been reported in 1
      percent of cases. The peroneal nerve localizaton has not been reported to date.
      We underline difficulties of diagnosis inherent to this particular localization.

PMID- 17028551
TI  - [Idiopathic chronic dysautonomia: when should the diagnosis be made?].
AB  - INTRODUCTION: Chronic autonomic disorders may complicate a wide range of
      conditions which can be divided into secondary, due to specific diseases, and
      primary, in which no cause has been determined. CASE REPORT: We report the case
      of a 43-year-old woman, who presented a chronic autonomic failure, which had
      begun by symptomatic orthostatic hypotension. Progressively, syncopes became
      daily, causing considerable discomfort associated with other signs of sympathic
      dysfunction: unilateral Horner's syndrome, diarrhea and hypohidrosis. The
      autonomic involvement was confirmed by study of the cardiovascular responses to
      tilt-up and electrophysiological autonomic testing. Etiologic search for a
      chronic acquired neuropathy (diabetes, amyloidis, paraneoplastic) or an inherited
      neuropathy was not conclusive. After five years, dysautonomic symptoms increased,
      but remained isolated. The physical examination did not show other clinical
      abnormalities such as cerebellar, pyramidal or extrapyramidal failure in favor of
      a multiple system atrophy or Parkinson's disease. All these data suggest the
      diagnosis of a primary autonomic failure. CONCLUSION: The diagnosis of primary
      autonomic failure is difficult to make because it requires that all the
      investigations in search of an etiology are negative and a long follow-up to be
      sure that dysautonomic symptoms persist isolated after many years of progression.

PMID- 17028552
TI  - [Rapid sensory motor neuropathy after gastric restriction surgery].
AB  - INTRODUCTION: Central and peripheral neurological complications have been
      described in association with bariatric surgery over the last 20 years. CASE
      REPORT: A 40 year-old women developed a sensory motor neuropathy 3 months after a
      gastric restriction operation followed by a 30 kilograms weight loss. No specific
      vitamin or mineral deficiency was detected but she improved after multivitamin
      and minerals supplementation. CONCLUSION: Acute or subacute neuropathy may
      develop in 1 to 2p.cent of patients who undergo bariatric surgery. Its
      pathogenesis is not very clear but the most commonly associated factors are rapid
      weight loss and non-supplementation with vitamins and minerals post-operatively.

PMID- 17028553
TI  - [Fatal giant cell arteritis with severe bilateral involvement of the vertebral
      arteries].
AB  - With steroid therapy, it is commonly considered that prognosis is good in giant
      cell arteritis. However serious or even fatal complications may occur. Here we
      report the case of a patient who developed fatal giant cell arteritis with severe
      stenosis of both vertebral arteries and right carotid siphon. Several similar
      cases have been reported in the literature. Initially diagnosis may be difficult
      because neurological manifestations are intermittent and classical signs of giant
      cell arteritis may be lacking. In such condition the reason of poor outcome is
      unknown and therapy remains empiric.

PMID- 17028554
TI  - [Neurological complications of Herpes zoster].
AB  - INTRODUCTION: Herpes zoster is a disease which occurs secondary to the
      reactivation of varicella-zoster virus (VZV). Its frequency is high in the
      general population. STATE OF ART: Herpes zoster leads to numerous complications,
      among which there were neurological peripheral or central lesions. Antiviral
      treatment must be instituted, particularly if neurological complications develop,
      as soon as possible. Corticosteroid therapy can be used, especially in Ramsay
      Hunt syndrome or central nervous system involvement. CONCLUSION: Herpes-zoster is
      a frequent disease which can lead to serious neurological complications. Early
      treatment is necessary in order to improve functional outcome.

PMID- 17028555
TI  - [THE SFN INTERNATIONAL MEETING Alzheimer's disease and dementia].

PMID- 17028556
TI  - Transgenic mouse models for Alzheimer's disease: the role of GSK-3B in combined
      amyloid and tau-pathology.
AB  - Describing and understanding the pathological processes which devastate the brain
      of Alzheimer's disease (AD) patients remains a major target for experimental
      biology. We approached this problem by generating different types of single and
      double transgenic mice that develop pathological hallmarks of AD. In APP-V717
      mice, the progression from intracellular amyloid to diffuse and senile plaques
      with vascular deposits, is preceded by early defects in cognition and LTP. In Tau
      P301L mice, the morbid tauopathy with intracellular filaments, cause mortality
      before age 1 year. Ageing APP-V717IxTau-P301L double tg mice (14-17 months) have
      combined AD-like pathology in hippocampus and cortex consisting of amyloid
      plaques and neurofibrillary tangles. Remarkably, while Tau-P301L mice die before
      age 1 year, the APP-V717IxTau-P301L double tg mice survive much longer, which
      correlates with alleviation of tauopathy in hindbrain, despite aggravation in
      forebrain. This hypothesis is corroborated in Tau-P301LxGSK-3B double transgenic
      mice, which have also an extended lifespan relative to Tau-P301L mice, that
      correlates with reduction of brainstem tauopathy. At the same time, Tau-P301LxGSK
      3B mice have dramatic forebrain tauopathy, with "tangles in almost all neurons",
      although without hyper-phosphorylation of Tau. The data corroborate the
      hypothesis that GSK-3B is the missing link between the amyloid and tau-pathology,
      and position GSK-3B as prominent player in the pathogenesis in AD.

PMID- 17028557
TI  - [From physiopathology to treatment of Alzheimer's disease].
AB  - The natural and molecular history of familial or sporadic Alzheimer's disease
      (AD) shows that APP (amyloid protein precursor) dysfunction is a consensual
      central etiological factor in Alzheimer's disease (AD). This is demonstrated by
      1) genetic defects involving APP gene or APP dysfunction (such as PS1 or PS2),
      leading to the formation of neocortical amyloid plaques in familial AD; 2)
      transgenic mice with these mutated genes that develop plaques; 3) both sporadic
      and familial AD develop plaques. But two alternatives to explain the
      physiopathology can be proposed: a gain of toxic function of AB peptide
      (reflected by the amyloid cascade hypothesis) or a loss of function of APP, a
      ubiquitous and well conserved protein with numerous possible neurotrophic
      activities. On the other hand, AD is also characterized by another inescapable
      degenerating process: tauopathy, an intraneuronal aggregation of tau proteins
      into neurofibrillary tangles. Remarkably enough, progression of tauopathy in
      neocortical areas fully explains the progressive clinical deficits of AD, from
      memory loss to aphasia, apraxia, agnosia. Also one has to bare in mind that most
      demented patients and most dementing neurodegenerative disorders have a
      tauopathy. From that, it is concluded that APP an Tau are solid therapeutic
      targets. But if we know that APP and Tau dysfunctions interact to boost
      neurodegeneration in AD, we still do no know what are the intraneuronal signaling
      pathways to activate or to inhibit to stop the degenerating process. There are
      many hypotheses and many possible approaches: the inhibition of toxicity of
      plaque, of AB protofibrils, or of AB oligomers inside or outside the neuron,
      using vaccination or ligands (Alzhemed). On the other hand, modulation of
      secretases that cleave APP by inhibiting those involved in the amyloidogenic
      pathway or by stimulating those of the non-amyloidogenic pathway, is a major
      route of research. Also modulation of kinases or phosphatases possibly involved
      in the aggregation of tau is also investigated. Because animal models are not
      perfectly relevant, at the end of the long and costly pathway of drug discovery,
      therapeutic trials are the only way to test these different hypotheses.

PMID- 17028558
TI  - [Neuropsychological markers for the diagnosis of Alzheimer's disease].
AB  - Better knowledge of the preclinical phase of Alzheimer's disease and of the
      symptomatic pre-dementia stage designated "mild cognitive impairment" will
      require considerable progress in our understanding of neuropsychological
      processes. The results of studies suggest that impaired performance in memory
      tests may serve as a marker for Alzheimer's disease. The best current predictors
      include stringent tests of episodic memory and recognition tests. The early
      stages of Alzheimer's disease also seem to involve subtle deficits in semantic
      memory and attentional processes. Face recognition and denomination seem to be
      useful tools. Greater accuracy and precision in the transitional zone between
      healthy aging and the first manifestations of Alzheimer's disease will require
      work combining data on neuropsychological profiles and neuroimaging.

PMID- 17028559
TI  - [Nosology of dementias: the neuropathologist's point of view].
AB  - The diagnosis of degenerative dementias heavily relies on the identification of
      neuronal or glial inclusions. Tauopathy is probably the largest group including
      Alzheimer and Pick disease, mutation of the tau gene, progressive supranuclear
      palsy, corticobasal degeneration, and argyrophilic grain disease. Lewy bodies,
      when numerous in the cerebral cortex, are usually associated with the cognitive
      deficit of Parkinson disease dementia or of dementia with Lewy bodies--both
      conditions being distinguished by clinical information. The inclusions of the
      dentate gyrus, only labeled by anti-ubiquitin antibodies, isolate a subgroup of
      fronto-temporal dementia (FTDu), sometimes familial and sometimes associated with
      amyotrophic lateral sclerosis. Mutations of the progranulin gene have been
      recently discovered among a significant proportion of these patients. Neuronal
      Intermediate Filament Inclusion Disease (NIFID) is a rare, apparently sporadic
      dementia, characterized by the presence of large inclusions in the cell body of
      many neurons. These inclusions react with antibodies directed against
      neurofilaments or against other intermediate filaments (such as alpha
      internexin). The diagnostic value of some of these inclusions allowing the
      classification of the degenerative dementias has been discussed. The link between
      the inclusions and the pathogenetic mechanism is indeed probably variable. It
      should however be stressed that whenever their composition has been elucidated,
      the inclusions have given important clues to the pathogenesis of the disease in
      which they had been found.

PMID- 17028560
TI  - [Alzheimer's disease and human memory].
AB  - Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to
      a detailed analysis into the framework of cognitive neuropsychology which aimed
      at describing the deficits of very specific processes. Beyond their clinical
      interest, these studies contributed to the modelisation of human memory thanks to
      the characterization of different memory systems and their relationships. The
      first part of this paper gives an overview of the memory deficits in Alzheimer's
      disease and insists on particular cognitive phenomena. Hence, several examples
      are developed in the domains of semantic memory (such as hyperpriming and
      hypopriming effects) and autobiographical memory. Recent results highlight the
      existence of severe autobiographical amnesia observed in all neurodegenerative
      diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's
      disease (showing that remote memories are better preserved than recent ones),
      reverse gradient in semantic dementia and no clear gradient in the frontal
      variant of frontotemporal dementia. The second part of this article presents
      advances in cognitive neuroscience searching to disclose the cerebral substrates
      of these cognitive deficits in Alzheimer's disease. The studies using functional
      imaging techniques are the most informative regarding this problematic. While
      showing the dysfunctions of an extended network, they emphasize the selectivity
      of cerebral damages that are at the root of very specific cognitive dysfunctions,
      coming close in that way to the conceptions of cognitive neuropsychology. These
      neuroimaging studies unravel the existence of compensatory mechanisms, which
      until recently were clearly missing in the literature on neurodegenerative
      diseases. These different researches lead to a wide conception of human memory,
      not just limited to simple instrumental processes (encoding, storage, retrieval),
      but necessarily covering models of identity and continuity of the subject, which
      interact in a dynamic way with eminently changing memory representations.

PMID- 17028561
TI  - Functional MRI in the early detection of dementias.
AB  - Functional MRI is a non-invasive imaging technology that can illuminate regional
      brain activity during the performance of a task, such as a memory paradigm, or at
      rest. fMRI data can be acquired during a session in which MRI data is also
      acquired to measure grey and white matter regional brain structure, and these
      measures can be analyzed together to investigate the relationships between
      altered regional brain function, structure, and cognitive task performance in
      neurologic illness. Data will be reviewed on the application of fMRI to the early
      detection of physiologic abnormalities associated with neurodegenerative diseases
      that cause dementia, and to differential diagnosis of dementias. Recent fMRI work
      will also be reviewed on the identification of abnormalities in regional brain
      function prior to dementia, the use of these measures to predict cognitive
      decline, and their application in investigations of alterations in regional brain
      networks that subserve cognitive function. Finally, the use of fMRI as a
      biomarker in clinical trials of putative neurotherapeutics for dementias will be
      discussed.

PMID- 17028562
TI  - [Brain profile of hypometabolism in early Alzheimer's disease: relationships with
      cognitive deficits and atrophy].
AB  - While accurate and early prediction of patients that will develop Alzheimer's
      disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive
      Impairment (MCI) state is of particular interest since it most conveniently
      represents the pre-dementia stage of AD. Consistently, the profile of brain
      functional alteration constantly evidenced in resting-state SPECT and PET studies
      is similar to that observed in mild AD, mainly involving the posterior cingulate
      and temporo-parietal regions. While the former is a characteristic feature of
      MCI, since it is present in each patient at this stage, the latter seems
      specifically associated with the future conversion to AD. Moreover, right temporo
      parietal hypometabolism has been found to be the best predictor of subsequent
      global cognitive decline, over and above neuropsychological and MRI volumetric
      measurements. This review also presents a discussion on the relationships between
      the brain profile of hypometabolism on the one hand, and cognitive impairment as
      well as cerebral structural alterations on the other. Thus, firstly, while
      functional impairment in the posterior cingulate region seems to be associated
      with deficits in retrieval of episodic memories in MCI, the relationship between
      right temporo-parietal hypometabolism and cognitive impairment is still obscure.
      However, several arguments point to its relation with visuo-spatial deficits,
      which are often associated with future conversion to AD. Secondly, the
      discordance between brain areas of major functional changes, and those of highest
      structural alterations, leads to some relevant questions about the relations
      between both pathological manifestations and their underlying mechanisms. More
      specifically, additional hypometabolism-inducing factors could occur in areas of
      highest hypometabolism compared to atrophy, i.e. mainly in posterior associative
      cortical regions, leading to genuine functional perturbation in early AD before
      the development of real atrophy and perhaps of disease as well. By contrast, the
      hippocampus is the main site of atrophy while its functional alteration is still
      debated, suggesting that compensation/protective mechanisms probably specifically
      occur in this structure to maintain a high level of metabolism relative to its
      structural alteration.

PMID- 17028563
TI  - [Update on the genetics of X-linked mental retardation].
AB  - Mutations in X-linked genes are likely to account for the observation that more
      males than females are affected with mental retardation. Causative mutations have
      been identified in both syndromic XLMR and in the genetically heterogeneous non
      syndromic forms of XLMR, without a clear clinical phenotype other than cognitive
      deficit. Progress in genome analysis and the establishment of large
      collaborations between clinical and molecular research teams, especially the
      European XLMR consortium, have led to the identification of 20 non-syndromic XLMR
      genes and 25 syndromic XLMR genes. Given the extensive heterogeneity of non
      syndromic XLMR, different strategies are used for the identification of new
      genes: linkage analysis, studies of balanced chromosomal rearrangements (X
      autosome translocations, microdeletions) and candidate genes strategies by
      mutation screening in regions of the X chromosome known to be involved in
      neuronal development and function. Delineating the monogenic causes of XLMR and
      their molecular and cellular consequences will provide insight into the
      mechanisms that are required for normal development of cognitive function in
      humans. Non syndromic XLMR proteins include 5 distinct classes: transmembrane
      receptors, small GTPases effectors or regulators, enzymes and translational
      regulators.

PMID- 17028564
TI  - [Contribution of ecological evaluation of executive disorders in multiple
      sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a major cause of neurological disability
      among young adults. The cognitive disorders are the second cause of alteration of
      quality of life after physical handicap and are often responsible for loss of
      social-occupational adaptability. The prevalence of cognitive disorders is 40 to
      65%. The alteration of executive functions predominates whereas instrumental
      functions are generally preserved. The assessment of these disorders is often
      underestimated by the usual battery of neuropsychological tests. However, the
      link between psychometric results and executive difficulties of daily life is
      uncertain. OBJECTIVES: To evaluate the sensitivity of an ecological test compared
      to standard psychometric tests in assessment of executive disorders in MS.
      METHODS: Twenty subjects with clinically definite MS were matched for age, sex
      and pre-morbid intellectual level with control subjects. A battery of
      neuropsychological and ecological tests was applied to all subjects. The
      performances on these tests formed a global score of executive function (SFE).
      The "paper and pencil" multiple errands test was used as the ecological test to
      examine planning and goal-oriented behavior. We also assessed fatigue and
      depression with the Fatigue Severity Scale and the Beck Depression Inventory.
      RESULTS: There was no significant differences between MS patients and controls in
      neuropsychological executive tests, except for verbal fluencies (p=0.01). The
      performances were significantly decreased in the MS group for the multiple
      errands test (p=0.01). 75% of MS subjects have a pathological score for this
      test. There was a significant link between the performances with this test and
      SFE (p=0.009). CONCLUSIONS: Executive disorders are underestimated in MS.
      However, we suggest that an ecological approach is more reliable than standard
      neuropsychological tests to estimate the cognitive difficulties in daily life in
      MS subjects. The results of our study favor further research to ascertain the
      usefulness of ecological assessment in MS.

PMID- 17028565
TI  - [Cognitive impairment and quality of life in multiple sclerosis patients].
AB  - INTRODUCTION: Cognitive disorders may bias perception of quality-of-life in
      patients with multiple sclerosis (MS). METHODS: Neuropsychological tests (WAIS
      vocabulary, Grober and Buschke, Stroop, WCST, WAIS-similitude, fluency,
      Hamilton's depression scale) along with a French health-related quality of life
      self questionnaire for MS patients (the SEP59) were performed by 117 MS patients
      with a minor cognitive impairment (Mini Mental State over 24) in order to explore
      the links between quality of life perception and cognitive functioning. RESULTS:
      Main Component Analysis and correlation analysis showed that cognitive impairment
      produced an overrating of the self perception of quality of life. Threshold
      analysis, splitting patients between the most and the less cognitively impaired,
      confirmed this relationship. CONCLUSION: The level of cognitive functioning must
      be considered with caution when analyzing health-related quality of MS patients.

PMID- 17028566
TI  - [Idiopathic acute transverse myelitis: application of new diagnosis criteria to
      17 patients].
AB  - INTRODUCTION: Idiopathic Acute Transverse Myelitis (ATM) is an inflammatory and
      immune-mediated disorder, distinct from infectious ATM, ATM of systemic lupus
      erythematosus or Sjogren's syndrome, and medullary manifestation of multiple
      sclerosis. Prognosis is not well-known. OBJECTIVE: To evaluate clinical,
      paraclinical and pronognosis data in patients selected with new diagnosis
      criteria, classically described in idiopathic ATM. METHODS: Seventeen patients
      with diagnosis criteria were retrospectively (1996-2005) studied. A telephone
      investigation was conducted in 2005 to obtained data on the clinical course.
      RESULTS: Seven men and 10 women, ranging in age from 15 to 75 years (mean: 39.8
      years) met these new criteria. Our study showed that epidemiological and clinical
      findings as well as laboratory results were in agreement with those presented in
      the literature. Conversely, prognosis was better since 76p.cent of the patients
      could walk without assistance. The clinical presentation of some of our patients
      and/or their progression towards other multifocal inflammatory disorders,
      suggests there might be links between ATM, neuromyelitis optica (NMO) and Acute
      Dissemined Encephalomyelitis (ADEM). CONCLUSION: Patients with idiopathic ATM,
      selected with new criteria, have a rather good prognosis. ATM seems to be part of
      a continuum of neuroimmunologic disorders including NMO or ADEM although reasons
      explaining distinct focal disorders remain unclear.

PMID- 17028567
TI  - [Late onset forms of myasthenia gravis. Comparison with early-onset myasthenia
      gravis].
AB  - INTRODUCTION: The incidence of myasthenia gravis appears to be increasing in
      elderly but few studies have been devoted to late onset myasthenia gravis.
      PATIENTS AND METHODS: We retrospectively compared myasthenic patients with an age
      at onset above or below 35 years which were observed in two departments of
      Neurology from 1980 to 2002. RESULTS: 81 cases were included, 28 of which were
      late onset myasthenia gravis. The two populations were similar in terms of sex
      ratio, clinical symptoms, course of the disease and therapeutic response. There
      was a trend for older patients to present more frequently at onset with dysphagia
      and axial or proximal involvement, and to have extra-ocular symptoms more
      quickly. Antibodies against acetylcholine receptor and striated muscle were
      statistically more frequent in elder patients. CONCLUSIONS: A late onset is not a
      factor of poor prognosis in myasthenia gravis and older patients must be treated
      in the same way than younger ones.

PMID- 17028568
TI  - [Finnish amyloid polyneuropathy in a French patient].
AB  - INTRODUCTION: Finnish amyloid variety is a rare familial amiloidosis
      polyneuropathy essentially observed in Finland. It concerns about six hundred
      people in the world in which five hundred reside in Finland. OBSERVATION: We
      report a case of a 58-year-old French woman with a 10-year history of lattice
      cornea dystrophy. She consulted in January 2004 for impaired swallowing, facial
      paralysis principally of the right superior territory and symptoms of arthritis
      which had developed a few months earlier. Observation revealed facial cutis laxa,
      tongue amyotrophy and some fasciculation. Electroneuromyography showed chronic
      neurogenic involvement of the facial muscles. Limbs and the sympathetic neuronal
      system were free of involvement. Pathological examination revealed areas of peri
      vascular amiloid deposits. Molecular biology confirmed the diagnosis of Finnish
      amiloidosis: substitution of aspartic acid by tyrosine in the 187 codon in the
      9th chromosome (gelsoline gene). This mutation has been previously found in
      Denmark and the Czech Republic. CONCLUSION: Finnish amiloidosis is a familial
      polyneuropathy characterized by an association of cornea lattice dystrophy, cutis
      laxa and a chronic neurogenic involvement of the cranial nerves. Two mutations
      are known. Life expectancy is not affected, but quality of life is altered.

PMID- 17028569
TI  - [Diffuse lower motor neuron disease in a carcinomatous meningitis].
AB  - INTRODUCTION: Between 4 and 15% of solid cancers are associated with
      carcinomatous meningitis ant its unfavorable prognosis. The clinical presentation
      of neoplastic meningitis typically associates cerebral signs, cranial nerve
      involvement, and medullary or radicular symptoms. OBSERVATION: We report a case
      of a 58-year-old woman, with a history of breast cancer in remission since 8
      years, who presented an acute paraparesia and a pure motor deficit of the left
      arm. This diffuse lower motor neuron disease was the inaugural sign of
      carcinomatous meningitis. CONCLUSION: The diagnosis of cacinomatous meningitis is
      based on medullar MRI and lumbar puncture. In same cases, clinical signs are
      limited to a pure diffuse lower motor neuron disease.

PMID- 17028570
TI  - [Ischemic, an uncommon complication of Biermer disease (pernicious anemia)].
AB  - INTRODUCTION: Stroke in a young adult justifies an extensive etiologic workup.
      OBSERVATION: We present a 44-year-old women victim of a frontal ischemic stroke.
      Extensive evaluation was normal, except for high plasma level of homocysteine in
      the context of pernicious anemia, otherwise asymptomatic. DISCUSSION:
      Hyperhomocysteinemia is a known marker, and probably risk factor for stroke,
      fostering atherosclerosis and thrombosis. It can be found among individuals
      suffering from homocystinuria, in individuals homozygous for the MHTFR T allele
      but also when there is deficiency of vitamin B12 or folic acid. Although it is
      very seldom ascribed, pernicious anemia would be a cause of stroke, possibly
      though hyperhomocysteinemia.

PMID- 17028571
TI  - [Reversible acute postpartum cerebral angiopathy].
AB  - Acute cerebral angiopathy is a rare neuro-vascular complication in postpartum. In
      this setting, the implication of vasoconstrictive drugs used for lactation or
      deliverance hemorrhage inhibition has been established. This review aimed 1) to
      describe, epidemiologic, clinical and diagnostic features of this pathological
      condition. 2) To put in perspective this condition within the scope of
      neurovascular clinical syndrome of pregnancy.

PMID- 17028572
TI  - [Continuous subcutaneous infusion of apomorphine for the treatment of Parkinson's
      disease].
AB  - Apomorphine administered by subcutaneous infusion has been used efficiently in
      parkinsonian patients to treat severe motor fluctuations and levodopa-induced
      dyskinesias. Despite increasing evidence of its efficacy and its relative safety,
      apomorphine infusion therapy is still underused. This article reviews
      pharmacokinetic properties, efficacy, tolerability and indications of apomorphine
      infusion in Parkinson's disease.

PMID- 17028573
TI  - Itch/AIP4 mediates Deltex degradation through the formation of K29-linked
      polyubiquitin chains.
AB  - Deltex (DTX) and AIP4 are the human orthologues of the Drosophila deltex and
      Suppressor of deltex, which have been genetically described as being
      antagonistically involved in the Notch signalling pathway. Both genes encode E3
      ubiquitin ligases of the RING (Really interesting new gene)-H2 and HECT
      (Homologous to E6AP carboxyl terminus) families, respectively. In an attempt to
      understand the molecular basis of their genetic interactions, we studied the
      relationship between DTX and AIP4 in the absence of activation of the Notch
      pathway. We show here that both molecules interact and partially colocalize to
      endocytic vesicles, and that AIP4 targets DTX for lysosomal degradation.
      Furthermore, AIP4-generated polyubiquitin chains are mainly conjugated through
      lysine 29 of ubiquitin in vivo, indicating a link between this type of chain and
      lysosomal degradation.

PMID- 17028574
TI  - Acetylation is important for MyoD function in adult mice.
AB  - Acetylation is a post-translational modification that influences the activity of
      numerous proteins in vitro. Among them, the myogenic transcription factor MyoD
      shows an increased transcriptional activity in vitro when acetylated on two
      lysines (K): lysines 99 and 102. Here, we have investigated the biological
      relevance of this acetylation in vivo. Using specific antibodies, we show that
      endogenous MyoD is acetylated on lysines 99 and 102 in myoblasts. Moreover, we
      show the functional importance of acetylation in live animals by using a mutant
      of MyoD in which lysines 99 and 102 were replaced by arginines (R). Knock-in
      embryos homozygous for the MyoD(R99,102) allele expressed slightly reduced levels
      of MyoD but developed normally. However, the knock-in homozygous adult mice
      showed a phenotype that was almost identical to that of MyoD-knockout animals,
      including delayed muscle regeneration in vivo and an increased number of
      myoblasts but with reduced differentiation potential in vitro. Together, these
      results show the importance of MyoD acetylation for adult myogenesis.

PMID- 17028576
TI  - Magnetic imaging of a supercooling glass transition in a weakly disordered
      ferromagnet.
AB  - Spin glasses are founded in the frustration and randomness of microscopic
      magnetic interactions. They are non-ergodic systems where replica symmetry is
      broken. Although magnetic glassy behaviour has been observed in many colossal
      magnetoresistive manganites, there is no consensus that they are spin glasses.
      Here, an intriguing glass transition in (La,Pr,Ca)MnO3 is imaged using a variable
      temperature magnetic force microscope. In contrast to the speculated spin-glass
      picture, our results show that the observed static magnetic configuration seen
      below the glass-transition temperature arises from the cooperative freezing of
      the first-order antiferromagnetic (charge ordered) to ferromagnetic transition.
      Our data also suggest that accommodation strain is important in the kinetics of
      the phase transition. This cooperative freezing idea has been applied to
      structural glasses including window glasses and supercooled liquids, and may be
      applicable across many systems to any first-order phase transition occurring on a
      complex free-energy landscape.

PMID- 17028575
TI  - Dengue-virus-infected dendritic cells trigger vascular leakage through
      metalloproteinase overproduction.
AB  - Dengue virus (DV) is an important re-emerging arthropod-borne virus of global
      significance. The defining characteristic of DV infection-associated pathology is
      haemorrhagic fever, which often leads to a fatal shock-like syndrome (DHF/DSS)
      owing to an increase in vascular endothelial permeability. Here, we show, in a
      viral dose-dependent manner, that DV-infected immature dendritic cells
      overproduce soluble gelatinolytic matrix metalloproteinase (MMP)-9-and to a
      lesser extent MMP-2-which enhances endothelial permeability, but which are
      reduced by specific inhibitors and a neutralizing anti-MMP-9 antibody. This
      permeability was associated with a loss of expression of the platelet endothelial
      adhesion molecule 1 (PECAM-1) and vascular endothelium (VE)-cadherin cell
      adhesion molecules and redistribution of F-actin fibres. These in vitro
      observations were confirmed in an in vivo vascular-leakage mouse model. These
      results provide a molecular basis for DHF/DSS that could be a basis for a general
      model of haemorrhagic fever-inducing viruses, and identify a new therapeutic
      approach for the treatment of viral-induced vascular leakage by specifically
      targeting gelatinolytic metalloproteases.

PMID- 17028577
TI  - Exciton polarizability in semiconductor nanocrystals.
AB  - The response of charge to externally applied electric fields is an important
      basic property of any material system, as well as one critical for many
      applications. Here, we examine the behaviour and dynamics of charges fully
      confined on the nanometre length scale. This is accomplished using CdSe
      nanocrystals of controlled radius (1-2.5 nm) as prototype quantum systems.
      Individual electron-hole pairs are created at room temperature within these
      structures by photoexcitation and are probed by terahertz (THz) electromagnetic
      pulses. The electronic response is found to be instantaneous even for THz
      frequencies, in contrast to the behaviour reported in related measurements for
      larger nanocrystals and nanocrystal assemblies. The measured polarizability of an
      electron-hole pair (exciton) amounts to approximately 10(4) A(3) and scales
      approximately as the fourth power of the nanocrystal radius. This size dependence
      and the instantaneous response reflect the presence of well-separated electronic
      energy levels induced in the system by strong quantum-confinement effects.

PMID- 17028578
TI  - Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce
      irreversible cellular senescence.
AB  - The p16(INK4a) cyclin-dependent kinase inhibitor has a key role in establishing
      stable G1 cell-cycle arrest through activating the retinoblastoma (Rb) tumour
      suppressor protein pRb in cellular senescence. Here, we show that the p16(INK4a)
      /Rb-pathway also cooperates with mitogenic signals to induce elevated
      intracellular levels of reactive oxygen species (ROS), thereby activating protein
      kinase Cdelta (PKCdelta) in human senescent cells. Importantly, once activated by
      ROS, PKCdelta promotes further generation of ROS, thus establishing a positive
      feedback loop to sustain ROS-PKCdelta signalling. Sustained activation of ROS
      PKCdelta signalling irreversibly blocks cytokinesis, at least partly through
      reducing the level of WARTS (also known as LATS1), a mitotic exit network (MEN)
      kinase required for cytokinesis, in human senescent cells. This irreversible
      cytokinetic block is likely to act as a second barrier to cellular
      immortalization ensuring stable cell-cycle arrest in human senescent cells. These
      results uncover an unexpected role for the p16(INK4a)-Rb pathway and provide a
      new insight into how senescent cell-cycle arrest is enforced in human cells.

PMID- 17028579
TI  - A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated
      exocytosis.
AB  - Fusion of vesicles into target membranes during many types of regulated
      exocytosis requires both SNARE-complex proteins and fusogenic lipids, such as
      phosphatidic acid. Mitochondrial fusion is less well understood but distinct, as
      it is mediated instead by the protein Mitofusin (Mfn). Here, we identify an
      ancestral member of the phospholipase D (PLD) superfamily of lipid-modifying
      enzymes that is required for mitochondrial fusion. Mitochondrial PLD (MitoPLD)
      targets to the external face of mitochondria and promotes trans-mitochondrial
      membrane adherence in a Mfn-dependent manner by hydrolysing cardiolipin to
      generate phosphatidic acid. These findings reveal that although mitochondrial
      fusion and regulated exocytic fusion are mediated by distinct sets of protein
      machinery, the underlying processes are unexpectedly linked by the generation of
      a common fusogenic lipid. Moreover, our findings suggest a novel basis for the
      mitochondrial fragmentation observed during apoptosis.

PMID- 17028580
TI  - Probing cell-division phenotype space and Polo-like kinase function using small
      molecules.
AB  - Cell-permeable small molecules that inhibit their targets on fast timescales are
      powerful probes of cell-division mechanisms. Such inhibitors have been identified
      using phenotype-based screens with chemical libraries. However, the
      characteristics of compound libraries needed to effectively span cell-division
      phenotype space, to find probes that target different mechanisms, are not known.
      Here we show that a small collection of 100 diaminopyrimidines (DAPs) yields a
      range of cell-division phenotypes, including changes in spindle geometry,
      chromosome positioning and mitotic index. Monopolar mitotic spindles are induced
      by four inhibitors, including one that targets Polo-like kinases (Plks),
      evolutionarily conserved serine/threonine kinases. Using chemical inhibitors and
      high-resolution live-cell microscopy, we found that Plk activity is needed for
      the assembly and maintenance of bipolar mitotic spindles. Plk inhibition
      destabilizes kinetochore microtubules while stabilizing other spindle
      microtubules, leading to monopolar spindles. Further testing of compounds based
      on 'privileged scaffolds', such as the DAP scaffold, could lead to new cell
      division probes and antimitotic agents.

PMID- 17028581
TI  - Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance.
AB  - Polo-like kinases (Plks) have several functions in mitotic progression and are
      upregulated in many tumor types. Small-molecule Plk inhibitors would be valuable
      as tools for studying Plk biology and for developing antitumor agents. Guided by
      homology modeling of the Plk1 kinase domain, we have discovered a chemical series
      that shows potent and selective Plk1 inhibition. The effects of one such
      optimized benzthiazole N-oxide, cyclapolin 1 (1), on purified centrosomes
      indicate that Plks are required to generate MPM2 epitopes, recruit gamma-tubulin
      and enable nucleation of microtubules. The compound can also promote loss of
      centrosome integrity and microtubule nucleating ability apparently through
      increased accessibility of protein phosphatases. We show that treatment of living
      S2 cells with cyclapolin 1 leads to collapsed spindles, in contrast to the
      metaphase-arrested bipolar spindles observed after RNAi. This different response
      to protein depletion and protein inhibition may have significance in the
      development of antitumor agents.

PMID- 17028582
TI  - Discrimination learning induced by training with identical stimuli.
AB  - Sensory stimuli become easier to detect or distinguish with practice. It is
      generally assumed that the task-relevant stimulus dimension becomes increasingly
      more salient as a result of attentively performing the task at a level that is
      neither too easy nor too difficult. However, here we show improved auditory
      frequency discrimination following training with physically identical tones that
      were impossible to discriminate. We also show that learning transfers across tone
      frequencies and across modalities: training on a silent visuospatial computer
      game improved thresholds on the auditory discrimination task. We suggest that
      three processes are necessary for optimal perceptual learning: sensitization
      through exposure to the stimulus, modality- and dimension-specific attention, and
      general arousal.

PMID- 17028583
TI  - Limited transfer of learning between unimanual and bimanual skills within the
      same limb.
AB  - Although a limb's motion appears to be similar across unimanual and bimanual
      movements, here we demonstrate partial, but not complete, transfer of learning
      across these behavioral contexts, hidden learning that remains intact (but
      invisible) until the original context is again encountered, and the ability to
      associate two conflicting force fields simultaneously, one with each context.
      These results suggest partial, but not complete, overlap in the learning
      processes involved in the acquisition of unimanual and bimanual skills.

PMID- 17028584
TI  - An allocentric rather than perceptual deficit in patient D.F.
AB  - The perception/action model states that vision for perception and vision for
      action are processed in separate pathways. This model was inspired by
      observations in patient D.F. who seemed unable to use vision for perceptual tasks
      while retaining 'normal' visuomotor capacity. I found that D.F.'s performance is
      preserved in perceptual and visuomotor tasks when the required spatial
      information is hand-centered and impaired when the information is object
      centered.

PMID- 17028585
TI  - Force field effects on cerebellar Purkinje cell discharge with implications for
      internal models.
AB  - The cerebellum has been hypothesized to provide internal models for limb movement
      control. If the cerebellum is the site of an inverse dynamics model, then
      cerebellar neural activity should signal limb dynamics and be coupled to arm
      muscle activity. To address this, we recorded from 166 task-related Purkinje
      cells in two monkeys performing circular manual tracking under varying viscous
      and elastic loads. Hand forces and arm muscle activity increased with the load,
      and their spatial tuning differed markedly between the viscous and elastic
      fields. In contrast, the simple spike firing of 91.0% of the Purkinje cells was
      not significantly modulated by the force nor was their spatial tuning affected.
      For the 15 cells with a significant force effect, changes were small and
      isolated. These results do not support the hypothesis that Purkinje cells
      represent the output of an inverse dynamics model of the arm. Instead these
      neurons provide a kinematic representation of arm movements.

PMID- 17028586
TI  - Ongoing eye movements constrain visual perception.
AB  - Eye movements markedly change the pattern of retinal stimulation. To maintain
      stable vision, the brain possesses a variety of mechanisms that compensate for
      the retinal consequences of eye movements. However, eye movements may also be
      important for resolving the ambiguities often posed by visual inputs, because
      motor commands contain additional spatial information that is necessarily absent
      from retinal signals. To test this possibility, we used a perceptually ambiguous
      stimulus composed of four line segments, consistent with a shape whose vertices
      were occluded. In a passive condition, subjects fixated a spot while the shape
      translated along a certain trajectory. In several active conditions, the spot,
      occluder and shape translated such that when subjects tracked the spot, they
      experienced the same retinal stimulus as during fixation. We found that eye
      movements significantly promoted perceptual coherence compared to fixation. These
      results indicate that eye movement information constrains the perceptual
      interpretation of visual inputs.

PMID- 17028587
TI  - Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.
AB  - Anergic T cells have altered diacylglycerol metabolism, but whether that altered
      metabolism has a causative function in the induction of T cell anergy is not
      apparent. To test the importance of diacylglycerol metabolism in T cell anergy,
      we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate
      diacylglycerol-dependent signaling. Overexpression of DGK-alpha resulted in a
      defect in T cell receptor signaling that is characteristic of anergy. We
      generated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had
      more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction
      was impaired in DGK-alpha-deficient mice. When stimulated in anergy-producing
      conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced
      interleukin 2. Pharmacological inhibition of DGK-alpha activity in DGK-zeta
      deficient T cells that received an anergizing stimulus proliferated similarly to
      wild-type T cells that received CD28 costimulation and prevented anergy
      induction. Our findings suggest that regulation of diacylglycerol metabolism is
      critical in determining whether activation or anergy ensues after T cell receptor
      stimulation.

PMID- 17028588
TI  - RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling
      and thymocyte development.
AB  - RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase
      family with unknown physiological function. Here we demonstrate that Rhoh-/- mice
      have impaired T cell receptor (TCR)-mediated thymocyte selection and maturation,
      resulting in T cell deficiency. RhoH deficiency resulted in defective CD3zeta
      phosphorylation, impaired translocation of the signaling molecule Zap70 to the
      immunological synapse and reduced activation of Zap70-mediated signaling in
      thymic and peripheral T cells. Proteomic analyses demonstrated that RhoH is a
      component of TCR signaling and is required for recruitment of Zap70 to the TCR
      through interaction with RhoH noncanonical immunoreceptor tyrosine-based
      activation motifs (ITAMs). In vivo reconstitution studies also demonstrated that
      RhoH function depends on phosphorylation of the RhoH ITAMs. These findings
      suggest that RhoH is a critical regulator of thymocyte development and TCR
      signaling by mediating recruitment and activation of Zap70.

PMID- 17028589
TI  - T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase
      alpha.
AB  - T cell anergy has been correlated with defective signaling by the GTPase Ras, but
      causal and mechanistic data linking defective Ras activity with T cell anergy are
      lacking. Here we used adenoviral transduction to genetically manipulate
      nonproliferating T cells and show that active Ras restored interleukin 2
      production and mitogen-activated protein kinase signaling in T cells that were
      made anergic in vitro or in vivo. Diacylglycerol kinases (DGKs), which negatively
      regulate Ras activity, were upregulated in anergic T cells, and a DGK inhibitor
      restored interleukin 2 production in anergic T cells. Both anergy and DGK-alpha
      overexpression were associated with defective translocation of the Ras guanine
      nucleotide-exchange factor RasGRP1 to the plasma membrane. Our data support a
      causal function for excess DGK activity and defective Ras signaling in T cell
      anergy.

PMID- 17028590
TI  - RNA polymerase II C-terminal domain mediates regulation of alternative splicing
      by SRp20.
AB  - Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II
      (pol II) with cotranscriptional precursor messenger RNA processing, but little is
      known about the CTD's function in regulating alternative splicing. We have
      examined this function using alpha-amanitin-resistant pol II CTD mutants and
      fibronectin reporter minigenes. We found that the CTD is required for the
      inhibitory action of the serine/arginine-rich (SR) protein SRp20 on the inclusion
      of a fibronectin cassette exon in the mature mRNA. CTD phosphorylation controls
      transcription elongation, which is a major contributor to alternative splicing
      regulation. However, the effect of SRp20 is still observed when transcription
      elongation is reduced. These results suggest that the CTD promotes exon skipping
      by recruiting SRp20 and that this contributes independently of elongation to the
      transcriptional control of alternative splicing.

PMID- 17028591
TI  - Amino acid residues in Rag1 crucial for DNA hairpin formation.
AB  - The Rag proteins carry out V(D)J recombination through a process mechanistically
      similar to cut-and-paste transposition. Specifically, Rag complexes form DNA
      hairpins through direct transesterification, using a catalytic Asp-Asp-Glu (DDE)
      triad in Rag1. How is sufficient DNA distortion introduced to allow hairpin
      formation? We hypothesized that, like certain transposases, the Rag proteins
      might use aromatic amino acid residues to stabilize a flipped-out base. Through
      in vivo and in vitro experiments and structural predictions, we identified
      residues in Rag1 crucial for hairpin formation. One of these, a conserved
      tryptophan (Trp893), probably participates in base-stacking interactions near the
      cleavage site, as do Trp298, Trp265 and Trp319 in the Tn5, Tn10 and Hermes
      transposases, respectively. Other residues surrounding the catalytic glutamate
      (YKEFRK) may share functional similarities with the YREK motif in IS4 family
      transposases.

PMID- 17028594
TI  - Principles of micro-RNA production and maturation.
AB  - Micro-RNAs (miRNAs) are a class of approximately 22-nucleotide non-coding RNAs
      expressed in multicellular organisms. They are first transcribed in a similar
      manner to pre-mRNAs. The transcripts then go through a series of processing
      steps, including endonucleolytic cleavage, nuclear export and a strand selection
      procedure, to yield the single-stranded mature miRNA products. The transcription
      and processing of miRNAs determines the abundance and the sequence of mature
      miRNAs and has important implications for the function of miRNAs.

PMID- 17028595
TI  - Principles and effects of microRNA-mediated post-transcriptional gene regulation.
AB  - MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of
      many key biological processes. Recent advances in understanding the mechanism of
      RNA interference and miRNA-mediated mechanisms shed light on major principals of
      the formation of the regulatory complex and provide models to explain how these
      small regulatory RNA species interfere with gene expression and how they
      influence the translational status of the transcriptome.

PMID- 17028596
TI  - MicroRNAs and the hallmarks of cancer.
AB  - It has become clear that particular microRNAs (miRNAs) function either as tumour
      suppressors or oncogenes, whose loss or overexpression, respectively, has
      diagnostic and prognostic significance. In several cases, miRNAs have been shown
      to affect target genes that are involved in the control of cell proliferation and
      apoptosis. However, malignant tumours display additional traits beyond the
      acquisition of enhanced growth potential and decreased cell death. Malignant
      disease is associated with altered tumour-host interactions leading to sustained
      angiogenesis and the ability to invade and metastasize. It is possible that
      miRNAs may act as master regulators of these aspects of tumour biology.
      Bioinformatic analysis of putative miRNA binding sites has indicated several
      novel potential gene targets of cancer-associated miRNAs that function in aspects
      of cell adhesion, neovascularization and tissue invasion. Among others, we
      speculate that miRNAs may find new roles in the regulation of E-cadherin,
      integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase,
      adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met
      and CXCR-4 that underpin the tissue architectural changes associated with
      malignancy.

PMID- 17028597
TI  - miRNAs and apoptosis: RNAs to die for.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs of about 18-24 nucleotides in length
      that negatively regulate gene expression. Discovered only recently, it has become
      clear that they are involved in many biological processes such as developmental
      timing, differentiation and cell death. Data that connect miRNAs to various kinds
      of diseases, particularly cancer, are accumulating. miRNAs can influence cancer
      development in many ways, including the regulation of cell proliferation, cell
      transformation, and cell death. In this review, we focus on miRNAs that have been
      shown to play a role in the regulation of apoptosis. We first describe in detail
      how Drosophila has been utilized as a model organism to connect several miRNAs
      with the cell death machinery. We discuss the genetic approaches that led to the
      identification of those miRNAs and subsequent work that helped to establish their
      function. In the second part of the review article, we focus on the involvement
      of miRNAs in apoptosis regulation in mammals. Intriguingly, many of the miRNAs
      that regulate apoptosis have been shown to affect cancer development. In the end,
      we discuss a virally encoded miRNA that influences the cell death response in the
      mammalian host cell. In summary, the data gathered over the recent years clearly
      show the potential and important role of miRNAs to regulate apoptosis at various
      levels and in several organisms.

PMID- 17028598
TI  - A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes.
AB  - The known classes of genes that function as tumor suppressors and oncogenes have
      recently been expanded to include the microRNA (miRNA) family of regulatory
      molecules. miRNAs negatively regulate the stability and translation of target
      messenger RNAs (mRNA) and have been implicated in diverse processes such as
      cellular differentiation, cell-cycle control and apoptosis. Examination of tumor
      specific miRNA expression profiles has revealed widespread dysregulation of these
      molecules in diverse cancers. Although studies addressing their role in cancer
      pathogenesis are at an early stage, it is apparent that loss- or gain-of-function
      of specific miRNAs contributes to cellular transformation and tumorigenesis. The
      available evidence clearly demonstrates that these molecules are intertwined with
      cellular pathways regulated by classical oncogenes and tumor suppressors such as
      MYC, RAS and p53. Incorporation of miRNA regulation into current models of
      molecular cancer pathogenesis will be essential to achieve a complete
      understanding of this group of diseases.

PMID- 17028599
TI  - Tumour-related microRNAs functions in Caenorhabditis elegans.
AB  - Altering cell proliferation and differentiation are usually key events leading to
      cancer. As originally demonstrated by Sydney Brenner in 1960s, the nematode
      Caenorhabditis elegans represents an animal model of choice to study mechanisms
      important to maintain proper cellular behaviour. This round worm has helped to
      elucidate components as well as new cellular pathways required for animal
      development. Among them, the discovery of the programmed cell death and non
      coding RNAs (microRNAs) controlling gene expression are two remarkable examples.
      Recently, two studies have demonstrated, once again, that using C. elegans can
      help gathering insights on cellular mechanisms leading to tumour formation. Two
      microRNAs, miR-84 and miR-61, control the expression of the oncogene orthologues
      Ras and Vav indicating their capacity to act as tumour suppressors. These
      observations demonstrate that uncovering the function of microRNAs is important
      to increase our understanding of cancer.

PMID- 17028600
TI  - MicroRNAs and chromosomal abnormalities in cancer cells.
AB  - Over the past five decades, a plethora of nonrandom chromosomal abnormalities
      have been consistently reported in malignant cells facilitating the
      identification of cancer-associated protein coding oncogenes and tumor
      suppressors. The genetic dissection of hot spots for chromosomal abnormalities in
      the age of the sequenced human genome resulted in the discovery that microRNA
      (miRNA) genes, encoding for a class of small noncoding RNAs, frequently resides
      in such genomic regions. The combination of nonrandom chromosomal abnormalities
      and other types of genetic alterations or epigenetic events contribute to
      downregulation or overexpression of miRNAs. The consequent abnormal expression of
      miRNAs affect cell cycle, survival and differentiation programs and selective
      targeting of these noncoding genes could provide novel therapeutic options for
      killing the malignant cells.

PMID- 17028601
TI  - Viruses, microRNAs and cancer.
AB  - Viruses represent one of the main factors that cause normal cells to proliferate
      and to become malignant: up to 15% of all human cancers are associated with
      single or multiple virus infections, and several viruses have been recognized as
      causal agents of specific types of cancer. Viruses have evolved many strategies
      to prevent infected cells from becoming apoptotic and to evade the innate and
      adaptive immune responses of their hosts. The recent discovery that Epstein-Barr
      virus and other herpesviruses produce their own sets of micro (mi)RNAs brings an
      additional layer of complexity in this ongoing host-virus arms race and changes
      our initial views of the antiviral roles of RNA silencing in plants and insects.
      It seems that, rather than being inhibited by this process, many mammalian
      viruses can usurp or divert the host RNA silencing machinery to their advantage.
      Viral-encoded miRNAs can act both in cis, to ensure accurate expression of viral
      genomes, and in trans, to modify the expression of host transcripts. Here, we
      review the current knowledge on viral miRNAs and discuss how mammalian viruses
      can also perturb host miRNA expression. Those recent findings provide new
      insights into the role of viruses and miRNAs in cancer development.

PMID- 17028602
TI  - Implications of micro-RNA profiling for cancer diagnosis.
AB  - Micro-RNAs (miRNAs) are a large class of small non-coding RNAs that regulate
      protein expression in eucaryotic cells. Initially believed to be unique to the
      nematode Caenorhabditis elegans, miRNAs are now recognized to be important gene
      regulatory elements in multicellular organisms and have been implicated in a
      variety of disease processes, including cancer. Advances in expression
      technologies have facilitated the high-throughput analysis of small RNAs,
      identifying novel miRNAs and showing that these genes may be aberrantly expressed
      in various human tumors. These studies suggest that miRNA expression profiling
      can be correlated with disease pathogenesis and prognosis, and may ultimately be
      useful in the management of human cancer.

PMID- 17028622
TI  - Alveolar hemorrhage following allogeneic hematopoietic cell transplantation using
      reduced-intensity conditioning.
AB  - Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity
      conditioning (RIC) has lower morbidity and mortality compared to transplantation
      using myeloablative conditioning (MAC). The syndrome of alveolar hemorrhage, a
      life-threatening pulmonary complication of HCT, has not been well described after
      RIC HCT. We reviewed prospectively collected data on 206 RIC and 1112 MAC HCT
      performed between 1995 and 2004 to study the impact of conditioning regimen on
      the clinical features and outcome of alveolar hemorrhage. Alveolar hemorrhage
      occurred in 18 RIC HCT recipients (cumulative incidence 8% (95% confidence
      intervals (CI), 5-11%)) and 85 MAC HCT recipients (cumulative incidence 7% (95%
      CI, 6-8%), P = 0.56). The clinical presentation of hemorrhage in both cohorts was
      similar. Survival at 60 days from the onset of hemorrhage was 28% (95% CI, 7-49%)
      for RIC group compared to 26% (95% CI, 17-35%) after MAC HCT (P = 0.56). Reducing
      the intensity of preparative regimen does not protect against post transplant
      alveolar hemorrhage. Alveolar hemorrhage occurring after RIC or MAC HCT has
      similar incidence, clinical presentation, and associated high mortality.

PMID- 17028623
TI  - Reduced-intensity unrelated cord blood transplantation for treatment of
      metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor
      effect.
AB  - We report a 69-year-old man with cytokine-resistant metastatic renal cell
      carcinoma treated with reduced-intensity unrelated cord blood transplantation.
      The patient achieved durable donor engraftment with minimal graft-versus-host
      disease. The patient showed regression of metastatic disease, providing the first
      evidence of a graft-versus-tumor effect on a solid tumor resulting from cord
      blood graft.

PMID- 17028625
TI  - [You should not tolerate].

PMID- 17028624
TI  - Outcome of adult umbilical cord blood transplant patients admitted to a medical
      intensive care unit.
AB  - Umbilical cord blood transplant (UCBT) has emerged as an alternate source of stem
      cells for transplantation in patients with hematologic malignancies. However,
      outcomes of adult UCBT patients requiring ICU admission remain unknown. In order
      to identify predictors of ICU transfer and mortality in UCBT patients, the course
      and outcome of all adult (> or = 16 years old) patients who underwent UCBT
      between 1 January 1998 and 31 December 2003 at University Hospitals of Cleveland
      were analyzed. Forty-four patients underwent UCBT during the study period and 25
      (57%) required ICU transfer. Use of a myeloablative preparative regimen was a
      significant predictor of ICU transfer (P = 0.03). An infusion of higher numbers
      of nucleated cells was protective from ICU transfer (P = 0.05). For those
      patients transferred to the ICU, mortality was 72%. The univariate predictors of
      mortality, at the time of ICU admission were a high APACHE III score (P =
      0.0004), use of vasopressors (P = 0.03), and a low platelet count (P = 0.03). We
      conclude that transfer of UCBT patients to an ICU may be predicted by their
      preparative regimen, while ICU mortality may be predicted by physiologic
      parameters upon admission.

PMID- 17028626
TI  - [Vaccination--the story about that's what did not happen].

PMID- 17028627
TI  - [Possibilities to help in amyotrophic lateral sclerosis].

PMID- 17028628
TI  - [Pregnancy, birth and neurologic disease].

PMID- 17028629
TI  - [Epilepsy and pregnancy--drug use, seizure control, and complications].
AB  - BACKGROUND: There is insufficient knowledge about the effect of epilepsy and
      epilepsy treatment on pregnancy, and vice versa. The European Registry of
      Antiepileptic drugs and Pregnancy (EURAP) was therefore established in 1999. We
      here present the results from the Norwegian part of the study, with emphasis on
      attack control, use of antiepileptics and folate, presence of status epilepticus,
      attacks in connection with birth and complications in the pregnancy. MATERIAL AND
      METHOD: The study is prospective and observational. The women are offered 5
      consultations, 3 during pregnancy and 2 after birth. RESULTS: As of September
      2005, 296 pregnancies in 263 Norwegian women were included. In 220 pregnancies
      (74 %), the women were treated with a single antiepileptic drug, most often
      carbamazepine. In 187 pregnancies (63 %), the women were seizure free. In those
      with seizures, 17 % had an increase in seizure frequency during pregnancy and 15
      % had a decrease. Convulsive status epilepticus associated with delivery occurred
      in 1 % of the women and seizures associated with the delivery in 2.7 %. The
      consequences for the mother and the child were not as serious as previously
      reported. The frequency of complications during pregnancy and the sectio rate did
      not differ significantly from the average population. INTERPRETATION: Most women
      with epilepsy go through pregnancy and delivery without complications.
      Specialists should only follow up those with a suboptimal seizure control. The
      slightly increased teratogenic risk can be reduced by giving these women extra
      folate before the conception.

PMID- 17028630
TI  - [Sexual abuse of prepubertal children].
AB  - BACKGROUND: During the last 15 years, a considerable change has taken place
      regarding the understanding of anatomical and microbiological anogenital findings
      in children. At the end of the 1980s, abnormal findings were described in more
      than 50 % of allegedly abused children. Today such findings are described in 5 %.
      An important consequence of this change is that absence of abnormal findings
      should never be used to exclude abuse, not even abuse with anogenital
      penetration. The main reason for this change is increased knowledge about normal
      variation and healing after injury, as well as an improvement in standardisation
      of terminology. MATERIAL AND METHODS: This paper is based on relevant literature
      published on this topic. RESULTS AND CONCLUSIONS: During this period, several
      findings have been reclassified from abnormal to normal or non-specific. Examples
      of such findings are anal dilatation, large and gaping hymenal opening and narrow
      hymenal brim. Some of the previously reported cases of anogenital scarring are
      probably mis-classified normal structures. Research-based international
      classification scales are now established in order to aid the physician in
      diagnosing sexual abuse, and these are revised on a regular basis. It is
      currently common to classify medical findings into three main categories;
      normal/unspecific findings, indeterminate findings and diagnostic findings.

PMID- 17028631
TI  - [Risk factors for sudden cardiac death related to the long QT syndrome].
AB  - BACKGROUND: Long QT syndrome is a rare condition. The syndrome is characterised
      by a prolonged QT-interval corrected for heart rate (QTc). The typical clinical
      presentation is the occurrence of syncope or cardiac arrest in young and
      otherwise healthy individuals. Cardiac events can be precipitated by
      environmental factors and use of certain drugs. The purpose of the present study
      is to provide guidelines regarding risk factors that may worsen the syndrome,
      based on available literature. MATERIAL AND METHODS: PubMed was searched for all
      literature in English from 1966 through 2004 on the Long QT syndrome. The
      articles and their literature references were examined. Additional information
      was achieved from experienced colleagues and from some key sites on the internet.
      RESULTS: The symptoms of the Long QT syndrome are tachycardia, syncope or cardiac
      arrest, often related to psychological or physical stress in young, usually
      healthy individuals. The syndrome can be inherited or acquired and is commonly
      caused by mutations in the potassium channel or by lack of inactivation of the
      sodium channels. The most common causes of acquired conditions are electrolyte
      abnormalities, intracranial disease, dietary deficiencies, myocardial infarction,
      dilated cardiomyopathy, mitral valve prolapse, bradycardia, severe malnutrition
      among anorexic patients and the use of medication. INTERPRETATION: It is
      important to have knowledge about the Long QT Syndrome. The treatment is
      primarily to remove potential risk factors and medically to give beta-blockers or
      insert pacemakers or cardiac defibrillators.

PMID- 17028632
TI  - [Quality of life of patients with amyotrophic lateral sclerosis].
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) leads to loss of important body
      functions, a huge need for assistance and is associated with a low quality of
      life (QoL). We have investigated QoL in ALS patients treated by a
      multidisciplinary ALS team, and to which degree this team met the patients'
      needs. MATERIAL AND METHODS: The patients' health-related QoL was measured by use
      of SF-36, and content with the treatment offered by the team was evaluated
      through a structured interview of 14 ALS patients at the Neurological Department
      at Ulleval University Hospital, Oslo, Norway. RESULTS: The patients reported low
      scores for physical QoL, but mental QoL was close to that of the general
      population. The patients were generally content with the treatment given by the
      ALS team. They were most content with the practical help given to organize their
      homes and the accessibility of different members of the team. They were least
      content with the psychological help and the information given to their relatives.
      Content with treatment was not correlated with self-perceived QoL or with
      physical disability. INTERPRETATION: Our findings suggest that the patients are
      content with the ALS team, but that their psychological reactions and information
      to relatives are not handled well enough. Most ALS patients treated by the ALS
      team experience their life as meaningful, regardless of their degree of
      neurological dysfunction.

PMID- 17028633
TI  - [Communication aids in amyotrophic lateral sclerosis].
AB  - BACKGROUND: Many patients with amyotrophic lateral sclerosis lose the ability to
      speak, and in late-stage disease also the ability to communicate through
      gestures. Social isolation is one of the greatest burdens of this disease.
      Implementation of alternative and augmentative communication can increase the
      quality of life even in advanced disease. MATERIALS AND METHODS: We have
      systematically recorded alternative and augmentative communication aids given to
      patients treated by the amyotrophic lateral sclerosis team at Ulleval University
      Hospital from 1998 to 2005, and evaluated the results in the light of current
      literature. RESULTS: 62 out of 92 patients received alternative and augmentative
      communication aids. Alternative and augmentative communication was more often
      used by female than male patients (p = 0.01). Except for two who developed
      dementia, all patients were able to express basic needs until the terminal stage
      of the disease. INTERPRETATION: Most patients retain enough mobility of head and
      eyes to use communication aids until the terminal stage. Physicians must know the
      possibilities and limitations of assisted and augmentative communication in order
      to give appropriate treatment and information, also concerning life-sustaining
      treatment.

PMID- 17028634
TI  - [Echinacea spp. (coneflower) and upper respiratory tract infections].

PMID- 17028636
TI  - [The Norwegian vaccination program].
AB  - Development of vaccines has in many ways been the art of the possible, using
      current knowledge about infections and microbes to devise new products. The aim
      of every vaccination is to prevent disease, but use of vaccines within
      vaccination programs is usually targeted not only to protect the individual, but
      also to changing the epidemiology of the disease. Several new vaccines will
      become available during the next decade, but the vaccination program will
      probably not be dramatically changed. Increased knowledge about the immune system
      might, in a longer time perspective, make it possible to rebuild a vaccination
      program on a new basis. Immunisations can perhaps be used for targeting the
      immune system in ways that still give protection against the specific infections,
      but in addition lead to better health through general protection against
      diseases, less allergy and less autoimmune diseases than we have today.

PMID- 17028635
TI  - [The cow, the boy and the lymph node--immunological principles for vaccines].
AB  - Vaccines stimulate the immune system by activating professional antigenpresenting
      cells, such as dendritic cells. Dendritic cells express a number of pattern
      recognition receptors (PRR) on their surface, receptors that recognize structures
      on viruses and bacteria. These receptors stimulate maturation of dendritic cells
      that thereafter migrate to regional lymph nodes where they present vaccine
      antigens to T-cells. PRR- ligands of the vaccine are decisive for the efficacy of
      the immune response. This article discusses cellular principles and mechanisms
      for vaccine responses; including antigen processing and presentation, T-cell
      circulation, Th1-, Th2- and CTL T-cell responses and T-B cell cooperation, as
      well as primary and secondary T and B cell responses and lymphocyte recirculation
      and homing.

PMID- 17028637
TI  - [Adverse events after vaccination].
AB  - When the diseases we try to prevent through vaccination are rare, we tend to
      focus more on the associated risks. Vaccination has led to unfortunate
      consequences, mainly due to production failure and inadequate control in earlier
      years. The requirements for vaccine control are now so rigorous that the risk for
      such occurrences is close to zero. Local and mild systemic reactions to vaccines
      are rather common, and are usually well known and described in detail when a
      vaccine is licensed. Some vaccine reactions are however so rare that they only
      will be discovered through surveillance after the vaccine has become available
      for routine use. Suspicion of adverse events will now normally arise through the
      official notification systems for adverse events. Large epidemiological studies
      are often necessary to decide whether there is a causal relationship or only a
      coincidence. Recording of adverse events following vaccination and transparency
      about their existence, are important issues in the work to maintain the
      credibility of vaccines.

PMID- 17028638
TI  - [Disability insurance--are drug addicts discriminated?].

PMID- 17028639
TI  - [Gender and language in primary health care].

PMID- 17028640
TI  - [Genefec--one more time].

PMID- 17028642
TI  - [Latin--keep the culture!].

PMID- 17028644
TI  - [Generic preparations--undocumented effects?].

PMID- 17028645
TI  - [Gaza--a comment].

PMID- 17028646
TI  - [Politics in the Tidsskrift].

PMID- 17028647
TI  - [Summer-juicy from Mads Gilbert].

PMID- 17028650
TI  - [Unexploded bombs in Gaza].

PMID- 17028653
TI  - [Surgical treatment og obstetric fistulas].

PMID- 17028656
TI  - The effect of Johne's disease on production traits in Romney, Merino and Merino x
      Romney-cross ewes.
AB  - AIM: To quantify the effects of clinical Johne's disease on the performance of
      Romney, Merino and Merino x Romney-cross ewes. METHODS: The performance of ewes
      was compared using eight birth cohorts (1971-1978). Merino and Merino-cross
      genotypes included New Zealand Merino and Australian Superfine Merino sources.
      Intensive monitoring of Johne's disease was undertaken over the production years
      1975-1982. Positive diagnostic evidence of Johne's disease was established post
      mortem from lesions of granulomatous enteritis associated with high numbers of
      acid-fast bacilli. Over years, data on a total of 2,341 Romney ewes and 1,292
      Merino and Merino x Romney-cross ewes were recorded, consisting of annual records
      of liveweight (LWT), greasy fleece weight (FWT), number of lambs born per ewe per
      year (NLB), and lifetime productivity of ewes. RESULTS: A total of 82 (3.5%)
      Romney ewes and 62 (4.8%) Merino and Merino x Romney-cross ewes were diagnosed
      with clinical Johne's disease over the 8-year monitoring period, equivalent to
      0.9% and 1.2% annual cases for these breeds, respectively, of the ewes present at
      mating. The percentage of clinical cases (p<0.04) and the age at death from
      Johne's disease (p<0.02) were lower for Romneys than for Superfine Merinos. The
      mean age of death from Johne's disease was 3.41 (standard error (SE) 0.06) years,
      lower than the mean disposal age from the flock of 5.03 (SE 0.02) years for
      clinically normal ewes (p<0.001). In their final year of production, ewes with
      clinical Johne's disease had lower LWT by 5.3 kg (10.5% of the mean; p<0.001),
      lower annual FWT by 0.54 (SE 0.10) kg (14.2%; p<0.001), fewer NLB by 0.15 (SE
      0.07) lambs (13%; p<0.05), and lower litter weaning weights by 3.6 (SE 1.3) kg
      (15%; p<0.01) compared with clinically normal ewes. The size of the production
      losses associated with Johne's disease depended on the age to which ewes
      survived. Considering all production years of ewes (up to 8 years), the total
      weight of lambs weaned by ewes with clinical Johne's disease was 30.9 (SE 3.4) kg
      lower (46%; p<0.001) than the total from clinically normal ewes. CONCLUSIONS:
      Clinical Johne's disease led to significant losses in LWT, FWT, NLB, and in the
      lifetime production of ewes, amounting overall to a 46% reduction in productivity
      (p<0.001). CLINICAL RELEVANCE: Productivity losses from clinical cases of Johne's
      disease would be of considerable economic importance in flocks with a high
      incidence of the disease. The lack of good diagnostic tests for Johne's disease
      in the live animal, and the lack of active surveillance programmes, has made it
      difficult to establish the true prevalence of Johne's disease in sheep flocks in
      New Zealand, and its economic consequences.

PMID- 17028657
TI  - Segmental axonopathy of Merino sheep in New Zealand.
AB  - AIM: To investigate an axonopathy of Merino sheep that caused progressive
      hindlimb ataxia and slight to moderate paresis, with the purpose of understanding
      its pathogenesis. METHODS: Tissues were fixed in buffered paraformaldehyde or
      paraformaldehyde and glutaraldehyde, processed into wax and epoxy resin,
      respectively, and examined by light and electron microscopy. Fresh frozen spinal
      cord and trigeminal nerve roots were subjected to homogenisation, centrifugation
      and two-dimensional electrophoresis. Selected protein spots were identified using
      matrix-assisted laser desorption ionisation (MALDI) mass spectrometry. RESULTS.
      By light microscopy, there were large pale foamy spheroidal axonal swellings
      affecting peripheral as well as central axons. By electron microscopy, these were
      shown to contain many membrane-bound vesicles. The main abnormalities in
      expressed proteins involved cytoskeletal elements and myosin heavy chain, the
      latter interpreted as associated with the molecular motor myosin Va. CONCLUSIONS:
      The disorder is the same as that described in Merinos in Australia as segmental
      axonopathy, and believed to have an inherited aetiology. The lesions and protein
      changes indicate abnormalities of the cytoskeleton, its relationship with the
      myelin sheath, and myosin Va molecular motor. The consequence appears to be
      abnormal axonal transport and inability to maintain the integrity of axons and
      their myelin sheaths.

PMID- 17028658
TI  - The effect of fertility control on the transmission of bovine tuberculosis in
      wild brushtail possums.
AB  - AIM: To determine the effect of fertility control on the rate of transmission of
      bovine tuberculosis (Tb), caused by Mycobacterium bovis, in brushtail possums
      (Trichosurus vulpecula). METHODS: At two study sites with a history of Tb
      infection in the resident possum population, a sample of adult male and female
      possums (n=50), determined by palpation to be Tb-free, was surgically sterilised
      by gonadectomy. A sample of untreated Tb-free male and female possums (n=54)
      served as controls. Each study site was trapped every 2 months over a 3-year
      period, and the Tb status of the individuals in the trial assessed. At the
      conclusion of the trial, all remaining experimental individuals were killed,
      necropsied and examined for characteristic lesions typical of Tb. The rate of
      transmission of Tb infection was estimated using the incidence of tuberculous
      cases in the experimental animals and comparing it between sites, sex and
      sterilisation treatment. RESULTS: Sterilisation by gonadectomy resulted in a
      reduction in the rate of transmission of Tb in male possums by 53%, but a
      corresponding increase in sterilised females for reasons that are still unclear.
      However, this interaction was statistically weak (p=0.10). When the sexes were
      combined, there was no overall effect of sterilisation on the rate of
      transmission of Tb (p=0.43). Sterility treatment notwithstanding, there was a
      highly significant difference in the rate of transmission between the sexes
      (p=0.01), being almost one order of magnitude higher in untreated males compared
      with untreated females. CONCLUSIONS: Although lacking strong statistical support,
      these results suggest that fertility control that targets endocrine control of
      fertility may provide some additional benefits for disease control over that
      achieved by reductions in population density, by reducing the rate of
      transmission of M. bovis in male possums. However, additional studies are needed
      to confirm the validity of these results. The large difference in the rate of
      transmission of M. bovis in untreated males compared with untreated females
      suggests that transmission of Tb among males may be an important driver of the
      dynamics of Tb infection in possums.

PMID- 17028659
TI  - Oral vaccination of brushtail possums with BCG: Investigation into factors that
      may influence vaccine efficacy and determination of duration of protection.
AB  - AIMS: To determine factors that may influence the efficacy of an oral pelleted
      vaccine containing Mycobacterium bovis bacille Calmette-Guerin (BCG) to induce
      protection of brushtail possums against tuberculosis. To determine the duration
      of protective immunity following oral administration of BCG. METHODS: In Study 1,
      a group of possums (n=7) was immunised by feeding 10 pellets containing dead
      Pasteur BCG, followed 15 weeks later with a single pellet of live Pasteur BCG. At
      that time, four other groups of possums (n=7 per group) were given a single
      pellet of live Pasteur BCG orally, a single pellet of live Danish BCG orally, 10
      pellets of live Pasteur BCG orally, or a subcutaneous injection of live Pasteur
      BCG. For the oral pelleted vaccines, BCG was formulated into a lipid matrix, and
      each pellet contained approximately 107 colony forming units (cfu) of BCG, while
      the vaccine injected subcutaneously contained 106 cfu of BCG. A sixth, non
      vaccinated, group (n=7) served as a control. All possums were challenged by the
      aerosol route with a low dose of virulent M. bovis 7 weeks after vaccination, and
      killed 7-8 weeks after challenge. Protection against challenge with M. bovis was
      assessed from pathological and bacteriological findings. In Study 2, lipid
      formulated live Danish BCG was administered orally to three groups of possums (10
      11 per group), and these possums were challenged with virulent M. bovis 8, 29 or
      54 weeks later. The possums were killed 7 weeks after challenge, to assess
      protection in comparison to a non-vaccinated group. RESULTS: The results from
      Study 1 showed that vaccine efficacy was not adversely affected by feeding dead
      BCG prior to live BCG. Feeding 10 vaccine pellets induced a level of protection
      similar to feeding a single pellet. Protection was similar when feeding possums a
      single pellet containing the Pasteur or Danish strains of BCG. All vaccinated
      groups had significantly reduced pathological changes or bacterial counts when
      compared to the non-vaccinated group. In Study 2, oral administration of Danish
      BCG induced protection against challenge with M. bovis, which persisted for at
      least 54 weeks after vaccination. Some protection was observed in possums
      challenged 54 weeks after vaccination, but this protection was significantly less
      than that observed in groups vaccinated 29 or 8 weeks prior to challenge. There
      was a strong relationship between the proportion of animals producing positive
      lymphocyte proliferation responses to M. bovis antigens and protection against
      challenge with M. bovis. CONCLUSIONS: Factors considered potentially capable of
      interfering with vaccination, including feeding dead BCG to possums prior to
      feeding live BCG, feeding multiple doses of BCG at one time, and changing strains
      of BCG, were shown not to interfere with the acquisition of protective immune
      responses in possums. Protection against tuberculosis was undiminished up to 29
      weeks after vaccination with BCG administered orally. It is concluded that
      vaccination of possums by feeding pellets containing BCG is a robust and
      efficient approach to enhance the resistance of these animals to tuberculosis.

PMID- 17028660
TI  - A possible predisposition to dilated cardiomyopathy in Huntaway dogs.
AB  - AIM: To compare the prevalence of dilated cardiomyopathy (DCM) in New Zealand
      Huntaway dogs with the prevalence of DCM in other breeds of dog. METHODS: The
      necropsy database at Massey University was used to identify cases of DCM
      diagnosed between January 1999 and March 2006. Dogs were considered to have DCM
      if echocardiographic, gross necropsy, or histological findings were consistent
      with this diagnosis. The prevalence in Huntaways was then compared with the
      prevalence observed in all breeds of dog, as well as the prevalence observed in
      large breeds of dog. RESULTS: Twelve dogs were identified with DCM. One was
      diagnosed using echocardiography, while the other 11 were diagnosed by gross
      necropsy examination. The gross diagnosis of DCM was confirmed histologically in
      6/11 dogs. The prevalence of DCM in Huntaways was significantly higher than the
      prevalence seen in all breeds of dog (p=0.008), and the prevalence in large
      breeds of dog (p=0.025). All four Huntaways diagnosed with DCM were male, and had
      an average age of 4 years. Three dogs presented with symptoms attributable to
      impaired heart function while one presented with symptoms of chronic renal
      failure. The duration of clinical symptoms prior to presentation ranged between 1
      day and 3 weeks. CONCLUSIONS: The results of this study suggest that Huntaways
      may be predisposed to the development of DCM. Although the increased prevalence
      in this breed was significant, only small numbers of affected Huntaways were
      identified, and additional cases are required to confirm these preliminary
      findings. CLINICAL RELEVANCE: Huntaways are the most common working dog in New
      Zealand. The premature loss of a working dog is expected to have a significant
      economic impact on farmers. Further investigation of DCM in Huntaways may allow
      measures to reduce the prevalence in this breed.

PMID- 17028661
TI  - The effect on creatinine kinase activity of freezing plasma from healthy foals.
AB  - AIM: To assess the stability of creatine kinase (CK) activity in plasma collected
      from healthy foals and frozen at -20 degrees C for up to 12 weeks. METHODS:
      Samples of venous blood drawn from 25 foals were analysed for CK activity soon
      after collection, and again after 1 and 12 weeks of freezing at -20 degrees C.
      RESULTS: CK activity decreased (p<0.001) between Week 0 and Week 1 and between
      Week 0 and Week 12. CONCLUSIONS AND CLINICAL RELEVANCE: Decreases in CK activity
      were statistically significant but clinically insignificant.

PMID- 17028662
TI  - Lesions in sheep following administration of a vaccine of a Freund's complete
      adjuvant nature used in the control of ovine paratuberculosis.
AB  - CASE HISTORIES: Occurrences of adverse reactions in seven sheep flocks in
      Australia following vaccination against paratuberculosis where veterinary
      attention was requested are reviewed. All cases occurred within the 3-year period
      following commencement of use of a vaccine of a Freund's complete adjuvant
      nature, at a time when approximately six million doses of vaccine had been
      administered. CLINICAL FINDINGS: In the first case, 26/58 (45%) Merino sheep
      vaccinated as adults had palpable tissue reactions at or near the site of
      vaccination; enlarged prescapular lymph nodes were palpated in 17 (29%), and nine
      (16%) sheep had both palpable lesions at the site of vaccination and enlarged
      prescapular lymph nodes. The reactions included caseous nodules up to 5.5 cm in
      diameter. In the other cases, fistulating or granulomatous wounds were
      occasionally found at the recommended site of injection behind the ear, and
      myiasis was rare. Occurrences of inappropriate choice of injection site were
      recorded, including injection into the axilla of two Merino rams, and lesions in
      the tissues of the maxilla and nose of almost 50% of 350 Border Leicester lambs.
      Four outbreaks of progressive paralysis due to injection into cervical
      musculature were reported, described as "OJD staggers" by producers. DIAGNOSIS:
      Granulomatous cellulitis and lymphadenitis associated with oil droplets typical
      of "oil granulomata". Injection of vaccine into the dorsal cervical area resulted
      in progressive paralysis due to myonecrosis and suspected granulomatous
      leptomeningitis. CLINICAL RELEVANCE AND CONCLUSIONS: Although lesions at and near
      the site of injection are common, adverse reactions to vaccination were rare and
      included mortality from cervical spinal injection, production losses from
      injection in the maxilla or axilla or if myiasis resulted, and potential
      marketing losses if animals or carcasses are discounted as a result of the
      lesions. Risk factors for adverse reactions included inadequate restraint of
      sheep, breed of sheep, experience of the operator, poor injection technique, and
      inappropriate placement of vaccine. Increasing attention to the proper restraint
      of animals, restricting vaccination to the recommended site behind the ear,
      careful placement of the vaccine into subcutaneous tissue to avoid drainage of
      vaccine material into tissues such as the spinal cord, and post-vaccination
      supervision to address welfare concerns should adverse reactions occur are
      recommended.

PMID- 17028664
TI  - Male pseudohermaphroditism in a Labrador Retriever, and a review of mammalian
      sexual differentiation.
AB  - CASE HISTORY: An 8-month-old Labrador Retriever was referred with a history of
      ambiguous external genitalia. CLINICAL FINDINGS AND TREATMENT: Clitoromegaly
      within apparent vulval folds, and an adjacent subcutaneous mass were noticed on
      external examination. An intra-abdominal testicle, with epididymis and suspected
      vas deferens ducts, was found during exploratory celiotomy. Incision over the
      subcutaneous mass revealed the accompanying testicle. Clitoridectomy was
      performed and an os clitoris removed. Normal juvenile testes were diagnosed on
      histology of the gonads. Chromosomal studies revealed a normal 78, XY male
      chromosomal constitution. Due to the combination of a male karyotype (78, XY),
      the presence of testicular tissue in the gonads, and the appearance of the
      external genitalia, a diagnosis of male pseudohermaphroditism (MPH) was made.
      CLINICAL RELEVANCE: This case presents the first report of MPH in a Labrador
      Retriever, and highlights the diagnostic steps recommended when confronted with a
      dog with ambiguous external genitalia.

PMID- 17028663
TI  - Canine gastrinoma: a case study and literature review of therapeutic options.
AB  - CASE HISTORY: A 6.2 kg, 8-year-old, spayed female Australian Terrier was
      presented with weight loss, inappetence, lethargy and a 2-day history of
      intermittent vomiting. CLINICAL FINDINGS: The dog had cranial abdominal pain and
      there was melaena present on digital rectal examination. Haematology revealed a
      marked, acute leucogram. DIAGNOSIS AND TREATMENT: Fasting serum gastrin levels
      were markedly elevated and gastrinoma was suspected. Treatment was initiated with
      omeprazole, ranitidine and sucralfate. The dog remained clinically normal for 26
      months, at which time exploratory surgery was undertaken and the dog subsequently
      euthanised due to extensive metastases. Histopathology and immunocytochemistry
      confirmed the diagnosis of metastatic gastrinoma. CLINICAL RELEVANCE: This is a
      rare condition infrequently reported. Although the number of cases treated with
      omeprazole are too few to draw firm conclusions, it would appear that proton pump
      inhibitors are useful and should be considered for cases of gastrinoma managed
      medically. Long-term prognosis is poor, and survival times range from 1 to 147
      weeks. Many treatment options are discussed in the medical literature though not
      all are feasible in veterinary patients.

PMID- 17028665
TI  - Confirmation of the occurrence of the chewing louse Bovicola (Lepikentron)
      breviceps (Insecta: Phthiraptera: Trichodectidae) on alpacas (Lama pacos) in New
      Zealand.

PMID- 17028666
TI  - Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic
      strategy for inflammatory disorders.
AB  - Interleukin (IL)-6 contributes to a myriad of physiologic and pathophysiologic
      processes. Among its many physiologic functions, IL-6 plays an active role in
      immunology, inflammatory responses, bone metabolism, arthritis and neoplasia.
      Overproduction of IL-6 has been implicated in the disease pathology of several
      inflammatory and autoimmune disorders, including rheumatoid arthritis,
      Castleman's disease, Crohn's disease and systemic-onset juvenile idiopathic
      arthritis. Interception of the IL-6 signaling pathway could thus represent a new
      treatment option for these diseases, given their refractory status to
      conventional therapy. Clinical studies with tocilizumab, a humanized monoclonal
      anti-IL-6 receptor antibody, have been undertaken to explore this option. Current
      short-term results indicate that tocilizumab dramatically improves disease
      activity and is well tolerated. Further long-term safety and efficacy studies are
      needed to confirm the therapeutic benefit of this antibody in inflammatory and
      autoimmune disorders.

PMID- 17028667
TI  - Ruboxistaurin.
AB  - Ruboxistaurin is a potent and specific inhibitor of the beta isoform of protein
      kinase C. Overactivation of protein kinase C has been demonstrated in patients
      with type 2 diabetes, and is postulated to play a major role in the pathogenesis
      of diabetic microvascular complications, which include diabetic retinopathy,
      neuropathy and nephropathy. The role of protein kinase C in promoting tissue
      injury in patients with diabetes, and the pharmacologic and clinical studies
      illustrating the potential of ruboxistaurin to reduce the burden of diabetic
      microvascular complications will be discussed in this article.

PMID- 17028668
TI  - Ropinirole treatment for restless legs syndrome.
AB  - In this paper we discuss therapy with ropinirole (known as adartrel in the United
      Kingdom) in patients with restless legs syndrome. Restless legs syndrome is
      characterized by an urge to move the legs, uncomfortable sensations in the legs
      and worsening of these symptoms during rest with at least temporary relief
      brought on by activity. Current recommendations suggest dopaminergic therapy
      (levodopa or dopamine receptor agonists like ropinirole) as the first-line
      treatment for restless legs syndrome. Based on the results of randomized, placebo
      controlled, double-blind trials, we conclude that ropinirole is effective in
      reducing symptoms of restless legs syndrome in the general population. Ropinirole
      has no serious or common side effects that would limit its use significantly.
      Rebound and augmentation problems are relatively rarely seen with ropinirole,
      although properly designed comparative trials are still needed to address this
      question. It must be noted, however, that most published studies with ropinirole
      compare this drug with placebo. Very few studies have compared ropinirole with
      other drugs (L-dopa, gabapentin, opioids, benzodiazepines, other dopaminergic
      agents and selegiline hydrochloride). No cost-effectiveness trial has been
      published yet. Treatment of restless legs syndrome with ropinirole shows it to be
      effective, well-tolerated and safe and it can be used in restless legs syndrome
      in general.

PMID- 17028669
TI  - Nanoparticle albumin-bound paclitaxel for treatment of metastatic breast cancer.
AB  - Two taxanes, paclitaxel and docetaxel, are among the most widely used
      chemotherapeutic agents in solid tumor oncology, with efficacy against tumors of
      the breast, lung, head and neck, ovary, prostate, stomach and urothelium. The
      taxanes have been studied extensively and have been proven effective for treating
      early and advanced breast cancer. However, paclitaxel and docetaxel are both
      highly hydrophobic compounds, requiring synthetic solvents for parenteral
      administration. The solvents in commercially available preparations cause life
      threatening toxic effects and decreased efficacy, and they are inconvenient to
      administer. Nanoparticle albumin-bound paclitaxel (nabP) is a novel, solvent-free
      formulation of paclitaxel. With nabP, in contrast to standard paclitaxel, life
      threatening hypersensitivity reactions have not been observed, and it can be
      administered safely without steroid and antihistamine premedication. Furthermore,
      nabP exploits cellular and tumor transport mechanisms to preferentially target
      tumor cells. Data from phase III studies of metastatic breast cancer demonstrated
      higher response rates, longer time to progression and an improved toxicity
      profile for nabP compared with standard paclitaxel. The U.S. Food and Drug
      Administration approved nabP in late 2004 for treatment of metastatic breast
      cancer after failure of an anthracycline-based regimen.

PMID- 17028670
TI  - The roles of mucus-associated bacteria in inflammatory bowel disease.
AB  - The etiology of inflammatory bowel disease (IBD) is currently unknown. Although
      there is convincing evidence supporting a critical role for micro-organisms in
      the pathogenesis of IBD, the specific organisms involved remain undetermined.
      Mucus-associated bacteria have recently been considered as likely candidates for
      involvement in IBD; indeed several mucus-associated bacteria species have been
      shown to induce IBD-like conditions in animal models, and some of these bacteria
      have been detected in human intestinal tissues. Further studies are required to
      investigate the possible role of mucus-associated bacteria in human IBD.

PMID- 17028671
TI  - Selective deoxygenation of sugar polyols to alpha,omega-diols and other oxygen
      content reduced materials--a new challenge to homogeneous ionic hydrogenation and
      hydrogenolysis catalysis.
AB  - An oxygen atom on every carbon--this is the problem! While nature provides linear
      C(3) to C(6) building blocks in the form of sugar alcohols in large and renewable
      abundance, they are overfunctionalized for the purpose of most chemical
      applications. Selective deoxygenation by anthropogenic catalyst systems may be
      one answer to this challenge.

PMID- 17028672
TI  - Structural and photophysical studies of phenanthrene adducts involving C6F5HgCl
      and [o-C6F4Hg]3.
AB  - Both pentafluorophenylmercury chloride and trimeric perfluoro-ortho-phenylene
      mercury interact with phenanthrene to form phosphorescent adducts which exhibit
      extended binary stacks in the solid state.

PMID- 17028673
TI  - Mechanistic investigation of CO2 hydrogenation by Ru(II) and Ir(III) aqua
      complexes under acidic conditions: two catalytic systems differing in the nature
      of the rate determining step.
AB  - Ruthenium aqua complexes [(eta(6)-C(6)Me(6))Ru(II)(L)(OH(2))](2+) {L = bpy (1)
      and 4,4'-OMe-bpy (2), bpy = 2,2'-bipyridine, 4,4'-OMe-bpy = 4,4'-dimethoxy-2,2'
      bipyridine} and iridium aqua complexes [Cp*Ir(III)(L)(OH(2))](2+) {Cp* = eta(5)
      C(5)Me(5), L = bpy (5) and 4,4'-OMe-bpy (6)} act as catalysts for hydrogenation
      of CO(2) into HCOOH at pH 3.0 in H(2)O. The active hydride catalysts cannot be
      observed in the hydrogenation of CO(2) with the ruthenium complexes, whereas the
      active hydride catalysts, [Cp*Ir(III)(L)(H)](+) {L = bpy (7) and 4,4'-OMe-bpy
      (8)}, have successfully been isolated after the hydrogenation of CO(2) with the
      iridium complexes. The key to the success of the isolation of the active hydride
      catalysts is the change in the rate-determining step in the catalytic
      hydrogenation of CO(2) from the formation of the active hydride catalysts,
      [(eta(6)-C(6)Me(6))Ru(II)(L)(H)](+), to the reactions of [Cp*Ir(III)(L)(H)](+)
      with CO(2), as indicated by the kinetic studies.

PMID- 17028674
TI  - The first member of the eleven-vertex azadicarbaborane series, 1,6,9-NC2B8H13,
      and its N-alkyl derivatives.
AB  - Reactions between closo-1,2-C(2)B(8)H(10) (1) and amines of general formulation
      R(1)R(2)NH (where R(1), R(2) = H, H; Me, H; t-Bu, H and Et, Et) resulted in a
      straightforward cluster expansion and formation of the 11-vertex arachno
      azadicarbaboranes of the 1,1-R(1),R(2-)1,6,9-NC(2)B(8)H(11) (2) cluster
      constitution (where R(1), R(2) = H, H 2a; Me, H 2b; t-Bu, H 2c and Et, Et 2d) in
      yields 10-75%, depending on the nature of the amine used. The reactions are the
      first example of a direct closo to arachno transformation in the area of cluster
      boron compounds. Compounds 2b and 2c were isolated in two isomeric forms anti-
      and syn- that differ in the positioning of the t-Bu substituent with respect to
      the bridging hydrogen site. Deprotonation of compounds 2 generally leads to
      removal of the bridging proton and formation of the [1,1-R(1),R(2-)1,6,9
      NC(2)B(8)H(11)](-) (2-) anions that, in the case of the monoalkylated Me and t-Bu
      derivatives, adopt only an anti configuration. The structure of anti-2c was
      determined by X-ray diffraction analysis and the geometries of the parent
      compound and the corresponding syn and anti isomers were optimised at the RMP2/6
      31G* level. The composition of all compounds is consistent with the results of
      mass spectrometry and multinuclear ((1)H and (11)B) spectroscopy complemented by
      two-dimensional [(11)B-(11)B]-COSY and (1)H{(11)B(selective)} NMR measurements.
      Experimental (11)B chemical shifts generally show acceptable agreement with
      theoretical values calculated by GIAO methods, in particular at GIAO-MP2/II,
      where possible.

PMID- 17028675
TI  - Pyridinyloxazolidines: versatile scaffolds for chiral catalyst construction.
AB  - Pyridinyloxazolidines are structurally versatile chiral ligand frameworks that
      are easily made and coordinated to Pd(II); the resulting complexes, which show
      significant steric and electronic differences from their oxazoline counterparts,
      as well as intermolecular H-bonding in the solid state, can be isolated in
      diastereomerically pure form and are remarkably resistant to hydrolysis.

PMID- 17028676
TI  - Synthesis, structure and fluorescent studies of novel uranium coordination
      polymers in the pyridinedicarboxylic acid system.
AB  - Self-assembly under hydrothermal conditions has been employed to synthesize
      several novel uranium-containing polymeric materials in the pyridinedicarboxylic
      acid (pydc) system. Uranium containing coordination polymers were synthesized
      utilizing 2,3-pyridinedicarboxylic acid (2,3-pydc), 2,4-pyridinedicarboxylic acid
      (2,4-pydc) and 2,6-pyridinedicarboxylic acid (2,6-pydc) as the organic linker.
      Furthermore, several bimetallic compounds were also synthesized, U-M-2,6-pydc (M
      = Cu, Ag, Pb). A new secondary building unit for uranium(vi) compounds has also
      been realized in compound 4 [(UO(2))(2)(C(7)H(3)NO(4))(O)(H(2)O)] through
      tetramer building units edge shared to form one-dimensional chains. Presented
      herein will be the syntheses, crystal structures and fluorescent properties of
      these uranium-containing compounds.

PMID- 17028677
TI  - Kinetics and mechanism of the reaction of [RuIII(edta)(H2O)]- with HOBr to form
      an intermediate RuV=O complex in aqueous solution.
AB  - The interaction of [Ru(III)(edta)(H(2)O)](-) (1) (edta =
      ethylenediaminetetraacetate) with the oxygen transfer agent HOBr, was studied
      kinetically as a function of [HOBr] and temperature (5-35 degrees C) at a fixed
      pH of 6.2. Spectroscopic evidence is reported for the formation of a high valent
      intermediate (edta)Ru(V)=O complex. Water soluble 2,2'-azobis(3
      ethylbenzithiazoline-6-sulfonate) (ABTS) was employed as a trap for this
      intermediate in order to gain further mechanistic information. Reactions were
      carried out under pseudo-first conditions for [ABTS] >> [HOBr] >> [1], and were
      monitored as a function of time for the formation of the one-electron oxidation
      product ABTS(*+). The reported kinetic data are interpreted in terms of a
      suggested reaction mechanism and discussed in reference to data reported before.

PMID- 17028678
TI  - Ferrocene-modified pyrimidine nucleosides: synthesis, structure and
      electrochemistry.
AB  - This paper reports syntheses, crystal structures and electrochemical results for
      two ferrocene(Fc)-modified pyrimidine nucleosides that could potentially be used
      for investigating electron transfer in DNA. Fc was directly attached to the 5
      position of deoxyuridine and deoxycytidine via the Stille coupling reaction. Fc
      modified uridine was incorporated into DNA trinucleotides with standard solid
      phase synthesis. The structures of corresponding detritylated compounds were
      determined by single-crystal X-ray analysis. Electrochemical investigations of
      all compounds by cyclic voltammetry revealed reversible redox processes.

PMID- 17028679
TI  - From structural properties of the EuIII complex with
      ethylenediaminetetra(methylenephosphonic acid) (H8EDTMP) towards biomedical
      applications.
AB  - Crystals of Eu(III) with ethylenediaminetetra(methylenephosphonic acid)
      (H(8)EDTMP) and with ethylenediaminetetraacetic acid (H(4)EDTA) have been
      synthesized in the same experimental conditions and their X-ray analyses have
      been performed. The EDTMP ligand wraps the Eu(III) ion in a fashion similar to
      its carboxylic analogue, EDTA, i.e. coordinating through two nitrogen atoms and
      four oxygen atoms in such a way that only one oxygen atom from each phosphonate
      group is bonded to the central ion. The coordination sphere is completed by two
      oxygen atoms of the bidentate carbonate anion in the case of the Eu(III)-EDTMP
      complex, whereas the inner sphere of the Eu(III)-EDTA crystal is completed by
      three water molecules. Spectroscopic studies (UV-Vis and (31)P NMR spectra) of
      Eu(III)-EDTMP solutions at controlled pH showed that the replacement of inner
      sphere water molecules and/or OH hydroxy groups by a carbonate anion in the
      Eu(III)-EDTMP complex at physiological pH results in the formation of
      [Eu(EDTMP)(CO(3))](7-) species which is thermodynamically stable and kinetically
      inert. The affinity of the carbonate anion towards the Eu(III)-EDTMP species was
      studied by analysis of f-f intensities and luminescence decay rates. The
      dissociation constant of the Eu(III)-EDTMP-carbonate complex was found to be
      approximately 43 mM. The presented results may be helpful in understanding the
      role played by the (153)Sm(III)-EDTMP complex known as Quadramet in the seeking
      of metastatic tissue in bones as well as possibly giving some premises for future
      ligand design of these types of complexes with lanthanide radionuclides.

PMID- 17028680
TI  - Complexation behaviour and stability of Schiff bases in aqueous solution. The
      case of an acyclic diimino(amino) diphenol and its reduced triamine derivative.
AB  - The copper(II), nickel(II), and zinc(II) complexes of the acyclic Schiff base
      H(2)L(A), obtained by [1 + 2] condensation of 1,2-ethanediamine,N-(2-aminoethyl)
      N-methyl with 3-ethoxy-2-hydroxybenzaldehyde, and of H(2)L(B), the reduced
      derivative of H(2)L(A), were prepared and their properties studied by IR, NMR and
      SEM-EDS. In these complexes, the metal ion is always located in the coordination
      chamber of the ligand delimited by two phenol oxygens and nitrogen atoms (either
      aminic or iminic). The coordination behaviour of H(2)L(A) and H(2)L(B) towards
      H(+), Cu(2+), Ni(2+) and Zn(2+) in aqueous solution at 298 K and mu = 0.1 mol dm(
      3) (Na)ClO(4) was also studied by potentiometric, NMR and UV-VIS measurements. In
      particular, potentiometric equilibrium studies indicate that H(2)L(A) is not
      stable enough to have a pH range in which it is the sole species in aqueous
      solution. In such a solution, the Schiff base forms over a limited pH range,
      between 6 and 10, with a maximum formation percentage at pH approximately 9. In
      addition, the involvement of imine nitrogens in the complexes markedly stabilises
      the azomethylene linkage, so that the metal complexes of H(2)L(A), particularly
      those of copper(II), are the species largely prevailing in solutions with pH
      >3.5. The stability constants of the complexes formed by metal ions with H(2)L(A)
      and H(2)L(B) follow the order Cu(2+) >> Ni(2+) > Zn(2+); distribution plots show
      that copper(II) gives complexes more stable with H(2)L(A), whereas Ni(2+) and
      Zn(2+) prefer the reduced ligand, H(2)L(B).

PMID- 17028681
TI  - Formation of a solubilized cobalt block oligomer from a M2L-type double helicate.
AB  - The multi-dentate ligand, 2,3,5,6-tetrakis(2,2'-bipyridyl)pyrazine (L) and
      divalent cobalt self-assemble to a block co-polymer-like oligomer in solution,
      which contains at least the L(7)Co(8) fragment. The extent of oligomerization is
      sensitive to the water content in acetonitrile solution. In the solid state, the
      simple monomer [LCo(2)(CH(3)CN)(4)][ClO(4)](4) is isolated. The X-ray structure
      of the crystallized material (containing four CH(3)CN solvate molecules) reveals
      a double-helical complex with two heptadentate Co(II) sites, and a helical pitch
      of approximately 28.1 A. Coupled Co(I/II) redox processes are observed between
      the two metal centres.

PMID- 17028682
TI  - Tricyclohexylphosphine-cyclopalladated ferrocenylimine complexes: synthesis,
      crystal structures and application in Suzuki and Heck reactions.
AB  - A series of novel tricyclohexylphosphine (PCy(3))-cyclopalladated ferrocenylimine
      complexes 2c-2g have been easily synthesized. These new palladacycles are
      thermally stable and are not sensitive to air and moisture. Their detailed
      structures have been determined by single-crystal X-ray analysis and six
      different types of intermolecular hydrogen bonds are found to be existed in the
      crystals of these complexes. The use of 2c-2g as catalysts for Suzuki and Heck
      reactions was examined. They were found to be very efficient for the Suzuki
      reaction of aryl chlorides with phenylboronic acid. Typically, using 0.1 mol% of
      catalyst in the presence of 1.5 equivalent of Cs(2)CO(3) as base in dioxane at
      100 degrees C provided coupled products in excellent yields. These complexes also
      displayed good activity in the Heck reaction of a range of aryl bromides with
      acrylic acid ethyl ester although they were not particularly useful for the
      activation of aryl chlorides.

PMID- 17028683
TI  - Functional polymers: scanning force microscopy insights.
AB  - Scanning force microscopy (SFM) and related techniques make it possible to
      visualize polymer systems with a molecular resolution. Beyond imaging, they also
      enable the unveiling of a variety of (dynamic) physico-chemical properties of
      both isolated polymer chains and their supramolecular architectures, including
      structural, mechanical and electronic properties. This article reviews recent
      progress in the use of SFM on polymers, with a particular emphasis on the
      mechanical properties of copolymers and single polymer chains, as well as on the
      bottom-up fabrication of supramolecular polymeric (helical) nanostructures in
      particular based upon pi-conjugated macromolecules as building blocks for
      nanoelectronics. Through a detailed understanding of the polymer behavior, we
      propose solutions for the generation of organic functional (nano)systems.

PMID- 17028684
TI  - On determining the nuclearity of iron sites in Fe-ZSM-5--a critical evaluation.
AB  - In order to interpret catalytic data on iron zeolites in terms of structure
      activity relationships, reliable characterisation methods are needed. In
      particular, the nuclearity of the iron species is an important issue, since it is
      often invoked to explain catalytic activity. In the present contribution, we
      address the problem of the nuclearity of the iron species in Fe-ZSM-5 by a
      combination of techniques, that is, UV-Vis, EXAFS, Magnetic Circular Dichroism
      (MCD) and magnetisation measurements. Based on an in-depth analysis of these
      data, we show that some of the current interpretations of UV-Vis and EXAFS
      spectra need to be revised.

PMID- 17028685
TI  - Parity conservation and polarization of differential cross sections in complex
      forming chemical reactions.
AB  - For complex-forming chemical reactions, such as atom-diatom insertion reactions,
      quantum scattering and quantum statistical calculations usually predict sharp
      forward/backward peaks in the Differential Cross Sections (DCS). Conversely, the
      corresponding classical calculations are unable to reproduce these peaks. We show
      here that the basic reason for such an intriguing failure is that parity
      conservation is ignored in classical mechanics. A by-product of the analysis is a
      simple parity-restoring approximation that might significantly increase the
      ability of classical mechanics to describe DCSs over the whole angular range for
      the title processes.

PMID- 17028686
TI  - Treating dispersion effects in extended systems by hybrid MP2:DFT calculations-
      protonation of isobutene in zeolite ferrierite.
AB  - We propose use of a hybrid method to study problems that involve both bond
      rearrangements and van-der-Waals interactions. The method combines second-order
      Moller-Plesset perturbation theory (MP2) calculations for the reaction site with
      density functional theory (DFT) calculations for a large system under periodic
      boundary conditions. Hybrid MP2:DFT structure optimisation for a cluster embedded
      in the periodic model is the first of three steps in a multi-level approach. The
      second step is extrapolation of the MP2 energy to the complete basis set limit.
      The third step is extrapolating the high-level (MP2) correction to the limiting
      case of the full periodic structure. This is done by calculating the MP2
      correction for a series of cluster models of increasing size, fitting an analytic
      expression to these energy corrections, and applying the fitted expression to the
      full periodic structure. We assume that, up to a constant, the high-level
      correction is described by a damped dispersion expression. Combining the results
      of all three steps yields an estimate of the MP2 reaction energy for the full
      periodic system at the complete basis set level. The method is designed for a
      reaction between a small or medium sized substrate molecule and a very large
      chemical system. For adsorption of isobutene in zeolite H-ferrierite, the
      energies obtained for the formation of different structures, the pi-complex, the
      isobutoxide, the tert-butoxide, and the tert-butyl carbenium ion, are -78, -73, 
      48, and -21 kJ mol(-1), respectively. This corresponds to corrections of the pure
      DFT (PBE functional) results by -62, -70, -67, and -29 kJ mol(-1), respectively.
      Hence, the MP2 corrections are substantial and, perhaps more importantly, not the
      same for the different hydrocarbon species in the zeolite. Coupled-cluster
      (CCSD(T)) calculations change the MP2 energies by -4 kJ mol(-1) (tert-butyl
      cation) or less (below +/-1 kJ mol(-1) for the other species).

PMID- 17028687
TI  - On the origin of the redshift of the OH stretch in Ice Ih: evidence from the
      momentum distribution of the protons and the infrared spectral density.
AB  - Recent measurements of the momentum distribution in water and ice have shown that
      the proton is in a considerably softer potential in ice Ih than in water or the
      free monomer. This is broadly consistent with the large red shift observed in the
      vibrational spectrum. We show that existing water models, which treat the
      intramolecular potential as unchanged by the hydrogen bonding are unable to
      reproduce the momentum distribution. In addition, even if they can substantially
      explain the red shift they are unable to explain the large increase in intensity
      observed in the infrared spectrum in going from the monomer to ice Ih. We show
      that the inclusion of a bond dipole derivative term is essential to explain the
      observed intensities in the infrared spectrum. Though this term is partially
      responsible for the softening of the effective potential of the proton we show
      that best agreement with the observed momentum distribution requires a further
      softening of the harmonic component of the intramolecular potential. We introduce
      an efficient normal-mode molecular dynamics algorithm for calculating the
      momentum distribution with path-integrals.

PMID- 17028688
TI  - Time-resolved photoelectron and photoion fragmentation spectroscopy study of 9
      methyladenine and its hydrates: a contribution to the understanding of the
      ultrafast radiationless decay of excited DNA bases.
AB  - The excited state dynamics of the purine base 9-methyladenine (9Me-Ade) has been
      investigated by time- and energy-resolved photoelectron imaging spectroscopy and
      mass-selected ion spectroscopy, in both vacuum and water-cluster environments.
      The specific probe processes used, namely a careful monitoring of time-resolved
      photoelectron energy distributions and of photoion fragmentation, together with
      the excellent temporal resolution achieved, enable us to derive additional
      information on the nature of the excited states (pipi*, npi*, pisigma*, triplet)
      involved in the electronic relaxation of adenine. The two-step pathway we propose
      to account for the double exponential decay observed agrees well with recent
      theoretical calculations. The near-UV photophysics of 9Me-Ade is dominated by the
      direct excitation of the pipi* ((1)L(b)) state (lifetime of 100 fs), followed by
      internal conversion to the npi* state (lifetime in the ps range) via conical
      intersection. No evidence for the involvement of a pisigma* or a triplet state
      was found. 9Me-Ade-(H(2)O)(n) clusters have been studied, focusing on the
      fragmentation of these species after the probe process. A careful analysis of the
      fragments allowed us to provide evidence for a double exponential decay profile
      for the hydrates. The very weak second component observed, however, led us to
      conclude that the photophysics were very different compared with the isolated
      base, assigned to a competition between (i) a direct one-step decay of the
      initially excited state (pipi* L(a) and/or L(b), stabilised by hydration) to the
      ground state and (ii) a modified two-step decay scheme, qualitatively comparable
      to that occurring in the isolated molecule.

PMID- 17028689
TI  - The heterogeneous kinetics of HOBr and HOCl on acidified sea salt and model
      aerosol at 40-90% relative humidity and ambient temperature.
AB  - The HOBr and HOCl uptake coefficient gamma on H(2)SO(4)-acidified submicron salt
      aerosol of known size distribution was measured in an atmospheric pressure
      laminar flow reactor. The interaction time of the trace gas with the aerosol was
      in the range 15 to 90 s and led to gamma values in the range 10(-4) to 10(-2).
      The acidity of the aerosol is essential in order to enable heterogeneous
      reactions of HOBr on NaCl, recrystallized sea salt (RSS) and natural sea salt
      (NSS) aerosols. Specifically, HOCl only reacts on acidified NSS aerosol with a
      gamma ranging from 0.4 x 10(-3) to 1.8 x 10(-3) at a relative humidity (rh) at 40
      and 85%, respectively. Uptake experiments of HOBr on aqueous H(2)SO(4) as well as
      on H(2)SO(4)-acidified NaCl, RSS or NSS aerosol were performed for rh ranging
      from 40 to 93%. The gamma value of HOBr on acidified NSS reaches a maximum gamma
      = 1.9 x 10(-2) at rh = 76 +/- 1% and significantly decreases with increasing rh
      in contrast to acidified NaCl and RSS aerosols whose gamma values remain high at
      gamma = (1.0 +/- 0.2) x 10(-2) at rh >/= 80%. An explanation based on the
      formation of an organic coating on NSS aerosol with increasing rh is proposed.

PMID- 17028691
TI  - Is perturbation DFT approach applicable to purely repulsive fluids?
AB  - A recently proposed third order + second order perturbation density functional
      theory (DFT) approach is tested for the validity and applicability to purely
      repulsive model fluids subjected to various external fields. Hard core repulsive
      Yukawa potential, point particle Yukawa potential, and inverse power potential
      are employed as sample models. Theoretical DFT results are compared with the
      corresponding simulation data obtained by grand canonical ensemble Monte Carlo
      simulation. This comparison indicates that the third order + second order
      perturbation DFT approach is suitable for these purely repulsive fluids only on
      condition of high accuracy of the imported bulk second order direct correlation
      function (DCF). However, in this case the origin of the successful performance
      somewhat differs from that observed for the mean field approximation applied to
      van der Waals fluids. In the present case it originates from the observation that
      the bulk second order DCF is strongly dependent on the density argument for the
      hard-core part, while for the distances exceeding the core dimension this
      dependence is considerably weaker.

PMID- 17028690
TI  - Detection of hydrogen bonding in solution: a 2H nuclear magnetic resonance method
      based on rotational motion of a donor/acceptor complex.
AB  - The effect of hydrogen bonding on the rotational correlation time of an H-bond
      acceptor, pyridine N-oxide-d(5), in various solvents was investigated using the
      (2)H spin-lattice relaxation time (T(1)). The results demonstrate a linear
      relationship between viscosity and measured rotational correlation times, an
      example of Stokes-Einstein-Debye behavior. The results also clearly demonstrate
      reduced rotational rates for the probe in hydrogen bonding solvents in comparison
      to solvents incapable of forming hydrogen bonds with the probe. The utility of
      this observation was exploited to estimate the association constant (K(a))
      through an NMR titration procedure. These results are presented as a new
      technique that can be applied to the characterization of hydrogen bonding in
      similar systems.

PMID- 17028692
TI  - On the nature of metallic nanoparticles obtained from molecular Co3Ru-carbonyl
      clusters in mesoporous silica matrices.
AB  - We report on the impregnation of THF solutions of the low-valent heterometallic
      cluster NEt(4)[Co(3)Ru(CO)(12)] into two mesoporous silica matrices, amorphous
      xerogels and ordered MCM-41, and a study of its thermal decomposition into
      metallic nanoparticles by X-ray diffraction, transmission electron microscopy and
      in situ magnetic measurements under controlled atmospheres. The decomposition of
      the cluster was monitored as a function of temperature by examining the chemical
      composition of the particles, their size distributions and their structures as
      well as their magnetic properties. Treatment under inert atmosphere (i.e. argon)
      at temperatures below 200 degrees C resulted in the formation of segregated
      spherical particles of hcp-ruthenium (2.3 +/- 1.0 nm) and hcp-cobalt (3.1 +/- 0.9
      nm). The latter is transformed to fcc-cobalt (3.2 +/- 1.0 nm) above 270 degrees
      C. At higher temperatures, Co-Ru alloying takes place and the Ru content of the
      particles increases with increasing temperature to reach the nominal composition
      of the molecular precursor, Co(3)Ru. The particles are more evenly distributed in
      the MCM-41 framework compared to the disordered xerogel and also show a narrower
      size distribution. Owing to the different magnetic anisotropy of hcp- and fcc
      cobalt, which results in different blocking temperatures, we were able to clearly
      identify the products formed at the early stages of the thermal decomposition
      procedure.

PMID- 17028693
TI  - Quantitative measurement and interpretation of optical second harmonic generation
      from molecular interfaces.
AB  - Second harmonic generation (SHG) has been proven a uniquely effective technique
      in the investigation of molecular structure and conformations, as well as
      dynamics of molecular interfaces. The ability to apply SHG to molecular interface
      studies depends on the ability to abstract quantitative information from the
      measurable quantities in the actual SHG experiments. In this review, we try to
      assess recent developments in the SHG experimental methodologies towards
      quantitative analysis of the nonlinear optical properties of the achiral
      molecular interfaces with rotational isotropy along the interface normal. These
      developments include the methodology for orientational analysis of the SHG
      experimental data, the experimental approaches for more accurate SHG
      measurements, and a novel treatment of the symmetry properties of the molecular
      polarizability tensors in association with the experimentally measurable
      quantities. In the end, the recent developments on the problem of surface versus
      bulk contribution in SHG surface studies is discussed. These developments can put
      SHG on a more solid foundation for molecular interface studies, and to pave the
      way for better understanding and application of SHG surface studies in general.

PMID- 17028695
TI  - Calculation of intermolecular interactions in the benzene dimer using coupled
      cluster and local electron correlation methods.
AB  - Potential energy curves for the parallel-displaced, T-shaped and sandwich
      structures of the benzene dimer are computed with density fitted local second
      order Moller-Plesset perturbation theory (DF-LMP2) as well as with the spin
      component scaled (SCS) variant of DF-LMP2. While DF-LMP2 strongly overestimates
      the dispersion interaction, in common with canonical MP2, the DF-SCS-LMP2
      interaction energies are in excellent agreement with the best available
      literature values along the entire potential energy curves. The DF-SCS-LMP2
      dissociation energies for the three structures are also compared with new
      complete basis set estimates of the interaction energies obtained from accurate
      coupled cluster (CCSD(T)) and DF-SCS-MP2 calculations. Since LMP2 is essentially
      free of basis set superposition errors, counterpoise corrections are not
      required. As a result, DF-SCS-LMP2 is computationally inexpensive and represents
      an attractive method for the study of larger pi-stacked systems such as truncated
      sections of DNA.

PMID- 17028694
TI  - Protein-bound chromophores astaxanthin and phytochromobilin: excited state
      quantum chemical studies.
AB  - We present an overview of excited state quantum chemical calculations aimed at
      elucidating controversial issues regarding the photochemistry of the protein
      bound chromophores astaxanthin and phytochromobilin. In particular, we show how
      the application of time-dependent density functional theory and other single
      reference quantum chemical excited state methods have contributed to shed new
      light on the origin of the >0.5 eV bathochromic shift of the electronic
      absorption by the carotenoid astaxanthin in the protein macromolecular complex
      crustacyanin, and the mechanism for C15-Z,syn --> C15-E,anti isomerization of the
      tetrapyrrole phytochromobilin that underlies the photoactivation of the plant
      photoreceptor phytochrome. Within the approximation that exciton coupling is
      neglected, the calculations on astaxanthin provide support for the notion that
      the bathochromic shift, which is responsible for the slate-blue coloration of
      lobster shell, is due to polarization rather than a conformational change of the
      chromophore in the protein-bound state. Furthermore, the polarization is
      attributed to a hydrogen-bonded protonated histidine residue. The calculations on
      phytochromobilin, in turn, suggest that a stepwise C15-Z,syn --> C15-E,syn
      (photochemical), C15-E,syn --> C15-E,anti (thermal) mechanism is much more
      favorable than a concerted, fully photochemical mechanism, and that neutral forms
      of the chromophore are much less likely to photoisomerize than the parent,
      protonated form. Accordingly, the calculations indirectly support the view that
      the photoactivation of phytochrome does not involve a proton transfer from the
      chromophore to the surrounding protein.

PMID- 17028696
TI  - Scalar relativistic calculations of hyperfine coupling tensors using the Douglas
      Kroll-Hess method with a finite-size nucleus model.
AB  - A scalar relativistic method to calculate hyperfine coupling tensors at the
      Douglas-Kroll-Hess level has been extended to incorporate a finite-size nucleus
      model using a Gaussian charge and magnetic moment distribution. Density
      functional calculations at gradient-corrected and hybrid functional levels have
      been carried out for the group 11 atoms and for a set of small group 12
      molecules, comparing nonrelativistic as well as scalar relativistic results at
      second-order Douglas-Kroll-Hess level with and without finite-size nucleus. While
      nonrelativistic calculations underestimate isotropic hyperfine couplings
      increasingly with increasing nuclear charge, scalar relativistic calculations
      with point nucleus provide somewhat overestimated values. Inclusion of the finite
      size nuclear model in the calculation of the wavefunction, and in the transformed
      hyperfine operators both decrease the magnitude of the hyperfine couplings. The
      effects, which are cumulative, improve agreement with experiment.

PMID- 17028697
TI  - How are the ready and unready states of nickel-iron hydrogenase activated by H2?
      A density functional theory study.
AB  - We have explored possible mechanisms for the formation of the catalytically
      active Ni(a)-S state of the enzyme, nickel iron hydrogenase, from the Ni*(r)
      (ready) or Ni*(u) (unready) state, by reaction with H(2), using density
      functional theory calculations with the BP86 functional in conjunction with a
      DZVP basis set. We find that for the reaction of the ready state, which is taken
      to have an -OH bridge, the rate determining step is the cleavage of H(2) at the
      Ni(3+) centre with a barrier of approximately 15 kcal mol(-1). We take the
      unready state to have a -OOH bridge, and find that reaction with H(2) to form the
      Ni(r)-S state can proceed by two possible routes. One such path has a number of
      steps involving electron transfer, which is consistent with experiment, as is the
      calculated barrier of approximately 19 kcal mol(-1). The alternative pathway,
      with a lower barrier, may not be rate determining. Overall, our predictions give
      barriers in line with experiment, and allow details of the mechanism to be
      explored which are inaccessible from experiment.

PMID- 17028698
TI  - Spatial distribution of stabilizer-derived nitroxide radicals during thermal
      degradation of poly(acrylonitrile-butadiene-styrene) copolymers: a unified
      picture from pulsed ELDOR and ESR imaging.
AB  - Double Electron-Electron Resonance (DEER) provides information on the spatial
      distribution of radicals on the length scale of a few nanometres, while Electron
      Spin Resonance Imaging (ESRI) provides information on a length scale of
      millimetres with a resolution of about 100 micrometres. Despite the gap between
      these length scales, results from the two techniques are found to complement and
      support each other in the characterization of the identity and distribution of
      nitroxide radicals derived from the Hindered Amine Stabilizer (HAS) Tinuvin 770
      in poly(acrylonitrile-butadiene-styrene) (ABS) copolymers. DEER measurements
      demonstrate that there is no significant formation of biradicals from the
      bifunctional HAS, and provide the distributions of local radical concentrations.
      These distributions are poorly resolved for model-free analysis of the DEER data
      by the Tikhonov regularization; the resolution was significantly improved by
      utilizing information obtained by ESRI. DEER data can be fitted with only one
      adjustable parameter, namely the average radical concentration, if 1D and 2D
      spectral--spatial ESRI results on both the spatial distribution of nitroxides and
      their distribution between the acrylonitrile--styrene-rich (SAN) and butadiene
      rich (B) microphases are considered.

PMID- 17028699
TI  - Synthesis and photophysical properties of a [60]fullerene compound with
      dimethylaniline and ferrocene connected through a pyrazolino group: a study by
      laser flash photolysis.
AB  - Pyrazolino[60]fullerene covalently-linked to ferrocene and N,N-dimethylaniline
      groups has been prepared and studied using time-resolved spectroscopic methods.
      The fluorescence quenching of the C(60) moiety indicates that charge-separation
      takes place via the singlet excited state of the C(60) moiety in both polar and
      non-polar solvents. The charge-separated state, in which an electron is localized
      on the C(60) sphere and a hole is located on the whole donor moieties of
      ferrocene, pyrazole, and N,N-dimethylaniline groups, has been confirmed by
      nanosecond transient spectra in the visible and near-IR spectral region. The
      lifetimes of the radical ion-pairs are as long as 30 - 50 ns in both polar and
      non-polar solvents.

PMID- 17028700
TI  - Competing through-space and through-bond, intramolecular triplet-energy transfer
      in a supposedly rigid ruthenium(II) tris(2,2'-bipyridine)--fullerene molecular
      dyad.
AB  - A ditopic ruthenium(II) tris(2,2'-bipyridyl)-based fullerene conjugate has been
      synthesized so as to separate the photoactive terminals by way of a short
      ethynylene spacer group that is expected to act as a rigid rod. Intramolecular
      triplet-energy transfer from the metal complex to the fullerene is quantitative
      at all temperatures and there is no indication for competing electron transfer.
      Temperature dependence studies indicate two pathways for triplet-energy transfer.
      An activationless route dominates at low temperature and is attributed to through
      bond electron exchange that takes place via super-exchange interactions. The
      triplet energy of the bridging unit lies well above that of the metal complex. An
      activated process is switched-on at high temperatures and is believed to involve
      through-space electron exchange within closed conformations. Molecular dynamics
      simulations predict that, in addition to an extended conformation, the linker can
      distort in such a way that the terminals come into orbital contact. In fact, the
      resultant closed conformation possesses an idealised geometry for fast electron
      exchange.

PMID- 17028701
TI  - Two grid refinement methods in the lattice Boltzmann framework for reaction
      diffusion processes in complex systems.
AB  - This paper studies the optimisation of a numerical model and a computer code to
      solve numerically reaction-diffusion processes in environmental or biological
      systems with complicated geometries and mixtures of reactions including time and
      spatial scales extending over several order of magnitude. In particular, we
      consider different grid refinement techniques in the framework of a lattice
      Boltzmann solver for reaction-diffusion systems. Two new grid refinement methods
      are proposed, which are both quantitatively good. The first method is based on
      the matching of the concentration profiles and fluxes across two adjacent sub
      domains, while the second method is based on nested subgrids. The focus of our
      study is the trade off between accuracy and CPU time. We show how the different
      parameters of the method, such as the refinement factors, the location of the
      boundary between different grids or coupling methods at the interface affect the
      quality of the numerical solution and the efficiency of the method.

PMID- 17028702
TI  - Scanning pyroelectric microscopy revealing the spatial polarity distribution in
      topologically centric crystals of trans-4-chloro-4'-nitrostilbene.
AB  - Scanning pyroelectric microscopy (SPEM) was applied to investigate grown-in
      polarity in trans-4-chloro-4'-nitrostilbene (CNS) single crystals. Sectors {011}
      and {011} were scanned for cross sections perpendicular to the a-direction. A
      rotational analysis for {011}, {011} faces was performed for a needle like
      crystal turned around the a-axis. All pyroelectric experiments confirm a bipolar
      grown-in state of polarity for sector involving the twofold axis b. These
      measurements agree with theoretical force field and stochastic calculations,
      predicting a bipolar state and a nearly identical extent of polarity for two
      different sectors.

PMID- 17028704
TI  - Triruthenium and triosmium carbonyl clusters containing chiral bidentate NHC
      thiolate ligands derived from levamisole.
AB  - The trinuclear complexes [M3(mu-Cl)(mu-S approximately CH)(CO)9] (M=Ru, Os; S
      approximately CH=1-ethylenethiolate-3-H-4-(S)-phenylimidazolin-2-ylidene) and
      [M3(mu-H)(mu-S approximately CMe)(CO)9] (M=Ru, Os; S approximately CMe=1
      ethylenethiolate-3-methyl-4-(S)-phenylimidazolin-2-ylidene) have been prepared by
      treating [Ru3(CO)12] and [Os3(CO)10(MeCN)2] with levamisolium chloride or [M3(mu
      H)(CO)11]- with methyl levamisolium triflate, respectively. The chiral N
      heterocyclic carbene-thiolate ligands S approximately CH and S approximately CMe
      arise from the oxidative addition of the C-S bond of levamisolium or methyl
      levamisolium cations to anionic trinuclear clusters.

PMID- 17028703
TI  - The role of electrochemistry in the development of pi-basic dearomatization
      agents.
AB  - Dihapto-coordination of aromatic molecules promotes numerous organic
      transformations that are not observed for the free aromatics. The development of
      osmium, rhenium, tungsten and molybdenum complexes that are capable of such
      binding is described in this perspective. The stability of these complexes
      strongly correlates to the metal d5/d6 reduction potential and electrochemical
      data has played a central role in their design.

PMID- 17028705
TI  - Crystal structure of lead(II) acetylacetonate and the structure of the
      acetylacetone solvated lead(II) ion in solution studied by large-angle X-ray
      scattering.
AB  - The crystal structure of bis(acetylacetonato)lead(II) and the structure of the
      acetylacetone solvated lead(II) ion in solution have been determined by single
      crystal X-ray diffraction and large-angle X-ray scattering (LAXS), respectively.
      The acetylacetone is deprotonated and acts as a bidentate anionic ligand (acac-)
      in the solid Pb(acac)2 compound. The lead(II) ion binds four oxygen atoms
      strongly in a nearly flat pyramidal configuration with Pb-O bond lengths in the
      range 2.32-2.37 A, and additionally three oxygens from neighboring complexes at
      3.01-3.26 A. Acetylacetone acts as a solvent (Hacac) at dissolution of lead(II)
      trifluoromethanesulfonate forming a pentasolvate with a mean Pb-O bond distance
      of 2.724(5) A. The 6s2 lone electron pair on the lead(II) ion becomes
      stereochemically active in the crystalline acetylacetonate complex, while it is
      inactive in the solvate in solution. The solution was also analysed using IR and
      1H NMR spectroscopy.

PMID- 17028706
TI  - New discrete and polymeric supramolecular architectures derived from dinuclear
      (bis-beta-diketonato)copper(II) metallocycles.
AB  - New examples of adducts between di- (and, in one instance, tetra-) functional
      nitrogen ligands and planar 'platform-like' dinuclear copper(II) complexes,
      [Cu2L2], incorporating the 1,3-aryl linked bis-beta-diketonato bridging ligand
      1,1'-(1,3-phenylene)-bis(4,4-dimethylpentane-1,3-dione) (H2L) have been
      synthesised. The X-ray structures of six adduct species are reported. The
      interaction of [Cu2(L)2] with the ditopic ligand aminopyrazine (apyz) yielded the
      sandwich-like tetranuclear species [(Cu2L2(apyz))2]. A variable-temperature
      magnetochemical investigation of this product indicated weak antiferromagnetic
      coupling between the (five-coordinate) copper centres, mediated by the 2
      aminopyrazine linkers. An analogous structure, [(Cu2L2(dabco))2] (dabco=1,4
      diazabicyclo[2.2.2]octane), was generated when dabco was substituted for
      aminopyrazine while use of 4,4'-dipyridyl sulfide (dps) and 4,4'-(1,3-xylylene)
      bis(3,5-dimethylpyrazole) (xbp) as the ditopic 'spacer' ligands resulted in
      polymeric species of type [Cu2L2(dps)]n and [Cu2L2(xbp)]n, respectively. These
      latter species exist as one-dimensional chain structures in which copper(II)
      centres on different dinuclear platforms are linked in a 'zigzag' fashion. In
      contrast, with 2,2'-dipyridylamine (dpa) a discrete complex of type [Cu2L2(dpa)2]
      formed in which one potential pyridyl donor from each 2,2'-dipyridylamine ligand
      remains uncoordinated. The use of the potentially quadruply-bridging
      hexamethylenetetramine (hmt) ligand as the linker unit was found to give rise to
      an unusual two-dimensional polymeric motif of type [(Cu2(L2)2)3(hmt)2]n. The
      product takes the form of a (6,3) network, incorporating triply bridging
      hexamethylenetetramine units.

PMID- 17028707
TI  - Assembled monolayers of Mo3S4(4+) clusters on well-defined surfaces.
AB  - A class of inorganic monolayers formed by assembling the molybdenum-sulfur
      cluster, Mo3S4(4+), onto a well-defined Au(111) surface is presented. The
      monolayers have been comprehensively characterized by electrochemistry, X-ray
      photoelectron spectroscopy (XPS), and in situ scanning tunneling microscopy (in
      situ STM). The voltammetric data show strong reductive and oxidative desorption
      signals from Au-S interactions, supported by the presence of both S and Mo
      signals in XPS. In situ STM shows many small pits in the dense adlayers uniformly
      spread over the surface, which is a typical feature of self-assembled monolayers
      (SAMs) of alkanethiols. The density of the pits is ca. 23 (+/-5)% and is
      significantly higher than for straight-chain alkanethiol SAMs with a single -SH
      group. The pit shapes are irregular, suggesting multiple Au-S interactions from
      Mo3S4(4+). High resolution images disclose bright round spots of ca. 8 A diameter
      representing individual molecules in the SAM. This is the first example of in
      situ monolayer formation by a metal-chalcogenide cluster directly anchored onto
      the gold surface through core ligands and offers a simple way to prepare a new
      class of functionalized inorganic monolayers.

PMID- 17028708
TI  - An improved method for the computation of ligand steric effects based on solid
      angles.
AB  - An improved algorithm has been designed to characterize ligand interactions in
      organometallic and coordination complexes in terms of the percentage of the metal
      coordination sphere shielded by a given ligand. The computations for ligand solid
      angles are performed numerically and employ introduced atomic radii that are
      larger than covalent but smaller than van der Waals radii. This approach enables
      facile evaluation of steric congestion in the metal coordination sphere,
      quantification of unfavorable interligand contacts, and in some cases prediction
      of the complex composition or ligand coordination on purely geometrical grounds.

PMID- 17028709
TI  - Basicity and coordination properties of a new phenanthroline-based bis
      macrocyclic receptor.
AB  - The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10
      triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic
      chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2,
      composed by two L1 moieties connected by an ethylenic bridge, are reported. Their
      basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and
      Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis,
      fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal
      complexes in aqueous solutions, while L2 can give both mono- and dinuclear
      complexes. In the mononuclear L2 complexes the metal is sandwiched between the
      two cyclic moieties. The metal complexes with L1 and L2 do not display
      fluorescence emission, due to the presence of amine groups not involved in metal
      coordination. These amine groups can quench the excited fluorophore through an
      electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to
      cleave the phosphate ester bond in the presence has been investigated by using
      bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2
      shows a remarkable hydrolytic activity, due to the simultaneous presence within
      this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act
      cooperatively in substrate binding, probably through a bridging interaction of
      the phosphate ester; the interaction is further reinforced by pi-stacking pairing
      and hydrophobic interactions between the phenanthroline unit(s) and the p
      nitrophenyl groups of BNPP.

PMID- 17028710
TI  - Syntheses and reactivity studies of solvated dirhenium acetonitrile complexes.
AB  - Fully and partially solvated triply-bonded [Re2]4+ complexes have been
      synthesized and their X-ray structures are described. A fully solvated dirhenium
      salt with BArf [tetrakis(3,5-bis(trifluoromethyl)phenyl)borate] as the counter
      anion [Re2(CH3CN)10][BArf]4 () has been characterized. The solubility of the
      complex in CH2Cl2 and THF in addition to CH3CN offers the possibility of improved
      reactivity. The structure of [Re2(micro-O)(CH3CN)10][BF4]4 () that possesses a
      linear [Re(III)-O-Re(III)]4+ unit is reported. Protonation reactions of cis
      Re2Cl2(dppm)2(O2CCH3)2 and trans-Re2Cl4(dppm)2 with HBF4.Et2O in acetonitrile
      afforded cis and trans [Re2(dppm)2(CH3CN)6][BF4]4 ( and ), respectively.
      Prolonging the reaction time, however, does not lead to fully solvated complex
      [Re2(CH3CN)10][BF4]4. The neutral nitrogen donor ligands pynp (2-(2-pyridyl)-1,8
      naphthyridine) and tznp (2-(2-thiazolyl)-1,8-naphthyridine) react readily with
      [Re2(CH3CN)10][BF4]4 to provide trans-[Re2(pynp)2(CH3CN)4][BF4]4 and trans
      [Re2(tznp)2(CH3CN)4][BF4]4. The X-ray structures trans-[Re2(pynp)2(CH3CN)4][BF4]4
      () and trans-[Re2(tznp)2(CH3CN)4][BF4]3[PF6] () have been determined.

PMID- 17028711
TI  - Effects of multiple ion loading on redox and luminescence properties of ruthenium
      trisphenanthroline crown ether hybrids.
AB  - Homoleptic and heteroleptic ruthenium trisphenanthrolines were prepared with
      azacrown ethers attached to the 4,7-positions of the phenanthrolines to maximise
      the electronic communication between the ruthenium and the crown ethers as
      complexation sites. Redox and spectral data were processed to explain the non
      steady trends in the absorption and emission spectra in the series. Addition of
      Ba2+ entailed large shifts in the redox potential (up to 370 mV) and in the
      emission spectra (up to 87 nm). Due to the crowded situation of the azacrown
      ether units in, this complex showed a non-linear behaviour both in the redox and
      emission properties upon loading with Ba2+ that is postulated to originate from
      the intermediate formation of sandwich type complexes.

PMID- 17028712
TI  - Solution chemistry of 1,15-bis(N,N-dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15
      pentaazapentadecane with metal ions of biological interest-Insights toward active
      metal ion containing therapeutics and diagnostic agents.
AB  - The equilibrium constants of Cu(II), Zn(II), Ca(II) and Gd(III) with 1,15-bis(N,N
      dimethyl)-5,11-dioxo-8-(N-benzyl)-1,4,8,12,15-pentaazapentadecane (La) have been
      studied at 25 degrees C and an ionic strength of 0.15 mol dm-3. Copper forms more
      stable complexes with La than the other metal ions investigated. This is probably
      due to the ease with which Cu(II) deprotonates the nitrogen donor atoms of the
      amide groups. UV/Vis spectrophotometric data indicate tetradentate binding of the
      ligand towards copper in [CuLaH-1] and pentadentate binding in [CuLaH-2]. Octanol
      water partition coefficients of Cu(II)-La complexes indicate that although these
      species are largely hydrophilic, approximately 5.62% of the [CuLaH-1] complex
      goes into the organic phase. This percentage may promote dermal absorption of
      copper with a calculated penetration rate of 3.75x10(-4) mm h-1. The [CuLaH-1]
      species which predominates at pH 7.4 is a poor mimic of native copper-zinc
      superoxide dismutase. Blood-plasma simulation studies predict that La is unable
      to increase the low molecular mass copper fraction in vivo. This has been
      confirmed by biodistribution patterns, which are similar to those of 64CuCl2.

PMID- 17028713
TI  - Synthesis and properties of Rh(I) and Ir(I) distibine complexes with
      organometallic co-ligands.
AB  - The first series of Rh(I) distibine complexes with organometallic co-ligands is
      described, including the five-coordinate [Rh(cod)(distibine)Cl], the 16-electron
      planar cations [Rh(cod)(distibine)]BF4 and [Rh{Ph2Sb(CH2)3SbPh2}2]BF4 and the
      five-coordinate [Rh(CO)(distibine)2][Rh(CO)2Cl2] (distibine=R2Sb(CH2)3SbR2, R=Ph
      or Me, and o-C6H4(CH2SbMe2)2). The corresponding Ir(I) species
      [Ir(cod)(distibine)]BF4 and [Ir{Ph2Sb(CH2)3SbPh2}2]BF4 have also been prepared.
      The complexes have been characterised by 1H and 13C{1H} NMR and IR spectroscopy,
      electrospray mass spectrometry and microanalysis. The crystal structure of the
      anion exchanged [Rh(CO){Ph2Sb(CH2)3SbPh2}2]PF(6).3/4CH2Cl2 is also described. The
      methyl-substituted distibine complexes are less stable than the complexes of
      Ph2Sb(CH2)3SbPh2, with C-Sb fission occurring in some of the complexes of the
      former. The salts [Rh(CO){Ph2Sb(CH2)3SbPh2}2]PF6 and [Rh{Ph2Sb(CH2)3SbPh2}2]BF4
      undergo oxidative addition with Br2 to give the known
      [RhBr2{Ph2Sb(CH2)3SbPh2}2]+, while using HCl gives the same hydride complex from
      both precursors, which is tentatively assigned as [RhHCl2{Ph2Sb(CH2)3SbPh2}]. An
      unexpected further Rh(III) product from this reaction, trans
      [RhCl2{Ph2Sb(CH2)3SbPh2}{PhClSb(CH2)3SbClPh}]Cl, was identified by a crystal
      structure analysis and represents the first structurally characterised example of
      a chlorostibine coordinated to a metal. [Rh{Ph2Sb(CH2)3SbPh2}2]BF4 reacts with CO
      to give [Rh(CO){Ph2Sb(CH2)3SbPh2}2]BF4 initially, and upon further exposure this
      species undergoes further reversible carbonylation to give a cis-dicarbonyl
      species thought to be [Rh(CO)2{Ph2Sb(CH2)3SbPh2}{kappa1Sb-Ph2Sb(CH2)3SbPh2}]BF4
      which converts back to the monocarbonyl complex when the CO atmosphere is
      replaced with N2.

PMID- 17028714
TI  - Syntheses and structural characterizations of 24-membered dimetal (Mn, Ni, Fe)
      macrocyclic complexes and the C-S bond formation between acetylacetone and a
      mercapto N-heterocycle.
AB  - An organic ligand 2,5-di(3-pentanedionylthio)-1,3,4-thiadiazole (H2L) reacts with
      metal (Mn, Ni, Fe) salts, resulting in 24-membered dimetal macrocyclic complexes
      [MnL(H2O)(dmso)](2).2dmso, [NiL(H2O)(dmf)](2).2dmf, [MnL(dmf)2]2 and
      [Fe2L2(solvent)2(SO4)] (solvent=dmso; H2O ; dmf). Di-manganese macrocyclic
      complexes [MnL(dmf)(dmso)]2 and [MnL(H2O)2](2).6H2O can also be obtained directly
      by aerobic assembly reaction of MnCl2, dipotassium 1,3,4-thiadiazole-2,5
      dithiolate (K2tdadt) and acetylacetone (H2acac) in various solvents, accompanying
      a C-S bond formation between acetylacetone and the mercapto N-heterocycle.
      Disulfide has been considered as the intermediate in the assembly reaction.
      Meanwhile an assembly reaction including MnCl2, 2-mercaptobenzimidazole and
      H2acac has produced an organic compound 2-(3-pentanedionylthio)benzimidazole with
      a new C-S bond. These dimetal complexes have similar macrocyclic structures, in
      which solvent molecules and sulfate coordinate to the octahedral metal in trans
      configuration, whereas a pair of water molecules are located in octahedral cis
      positions for owing to a small steric effect. A host cavity of sufficiently large
      size exists in the macrocyclic structure to trap the solvent molecules and the
      sulfate anion. The IR spectra have been used to assign the solvent molecules
      trapped and the sulfate anion which is shown as a bridged bidentate ligand.
      Thermal analyses show the stability of the macrocyclic backbone below 200 degrees
      C and gradual release processes of the trapped solvent molecules. Decomposition
      and oxidation of the dimetal macrocycle backbone occur at 300-500 degrees C,
      resulting in a metal sulfate. Further decomposition led to metal oxide at 500-600
      degrees C.

PMID- 17028715
TI  - o-Phenylene-bridged Cp/sulfonamido titanium complexes for ethylene/1-octene
      copolymerization.
AB  - The Suzuki-coupling reaction of 2-(dihydroxyboryl)-3,4-dimethyl-2-cyclopenten-1
      one and 2-(dihydroxyboryl)-3-methyl-2-cyclopenten-1-one with 2-bromoaniline
      derivatives affords cyclopentenone compounds from which cyclopentadiene
      compounds, 4,6-R'(2)-2-(2,5-Me2C5H3)C6H2NH2 and 4,6-R'(2)-2-(2,3,5
      Me3C5H2)C6H2NH2 are prepared. After sulfonation of the -NH2 group with p-TsCl,
      metallation is carried out by successive addition of Ti(NMe2)4 and Me2SiCl2
      affording o-phenylene-bridged Cp/sulfonamido titanium dichloride complexes, [4,6
      R'(2)-2-(2,5-Me2C5H2)C6H2NSO2C6H4CH3)]TiCl2 (R'=H, ; R'=Me, ; R'=F, ) and [4,6
      R'(2)-2-(2,3,5-Me3C5H)C6H2NSO2C6H4CH3)]TiCl2 (R'=H, ; R'=Me, ; R'=F, ). The
      molecular structures of and [2-(2,5-Me2C5H2)C6H4NSO2C6H4CH3)]Ti(NMe2)2 are
      determined by X-ray crystallography. The Cp(centroid)-Ti-N angle in is smaller
      (100.90 degrees) than that observed for the CGC (constrained-geometry catalyst),
      [Me2Si(eta5-Me4Cp)(NtBu)]TiCl2 (107.6 degrees) indicating a more "constrained
      feature" in than in the CGC. Complex shows the highest activity among the newly
      prepared complexes in ethylene/1-octene copolymerization but it is slightly
      inferior to the CGC in terms of activity, comonomer-incorporation ability, and
      molecular weight of the obtained polymers.

PMID- 17028717
TI  - Single molecule studies of DNA binding proteins using optical tweezers.
AB  - Optical tweezers have become a versatile tool in the biological sciences.
      Combined with various types of optical microscopy, they are being successfully
      used to discover the fundamental mechanism of biological processes. Recently, the
      study of proteins acting on DNA was aggressively undertaken at the single
      molecule level. Here, we review the most recent studies which have revealed the
      dynamic behavior of individual protein molecules at work on DNA, providing
      detailed mechanistic insight that could not be revealed, at least not easily,
      using bulk-phase or ensemble approaches.

PMID- 17028719
TI  - Evaluation of capillary ion exchange stationary phase coating distribution and
      stability using radial capillary column contactless conductivity detection.
AB  - The use of radial (across) capillary column capacitively coupled contactless
      conductivity detection is demonstrated as a simple and rapid technique for
      visualisation of stationary phase longitudinal coverage and coating stability in
      capillary ion exchange chromatography.

PMID- 17028718
TI  - Metabolic fingerprinting in disease diagnosis: biomedical applications of
      infrared and Raman spectroscopy.
AB  - The ability to diagnose the early onset of disease, rapidly, non-invasively and
      unequivocally has multiple benefits. These include the early intervention of
      therapeutic strategies leading to a reduction in morbidity and mortality, and the
      releasing of economic resources within overburdened health care systems. Some of
      the routine clinical tests currently in use are known to be unsuitable or
      unreliable. In addition, these often rely on single disease markers which are
      inappropriate when multiple factors are involved. Many diseases are a result of
      metabolic disorders, therefore it is logical to measure metabolism directly. One
      of the strategies employed by the emergent science of metabolomics is metabolic
      fingerprinting; which involves rapid, high-throughput global analysis to
      discriminate between samples of different biological status or origin. This
      review focuses on a selective number of recent studies where metabolic
      fingerprinting has been forwarded as a potential tool for disease diagnosis using
      infrared and Raman spectroscopies.

PMID- 17028720
TI  - Sensitive and rapid electrochemical bioassay of glycosidase activity.
AB  - Here we present a highly sensitive, rapid and simple electrochemical assay for
      glycosidases based on treatment of the glycosidase with the appropriate p
      nitrophenyl glycoside and anodic detection of released p-nitrophenol. The
      attractive characteristics of the new bioassay should facilitate advanced
      glycomic research and routine clinical diagnostics since glycosidases are
      associated with various diseases.

PMID- 17028721
TI  - Layer guided-acoustic plate mode biosensors for monitoring MHC-peptide
      interactions.
AB  - The transduction signals from the immobilisation of a class I heavy chain, HLA
      A2, on a layer guided acoustic plate mode device, followed by binding of beta(2)
      microglobulin and subsequent selective binding of a target peptide are reported.

PMID- 17028723
TI  - Apparent 'electrocatalytic' activity of multiwalled carbon nanotubes in the
      detection of the anaesthetic halothane: occluded copper nanoparticles.
AB  - The electrocatalytic detection of the anaesthetic halothane on a multiwalled
      carbon nanotube modified glassy carbon electrode is reported with a low limit of
      detection of 4.6 microM. A thorough investigation of the underlying cause of this
      apparent catalytic effect is undertaken by comparing the response of various
      carbon electrodes including glassy carbon, basal- and edge-plane pyrolytic
      graphite electrodes (bppg and eppg respectively) to increasing additions of
      halothane. The reduction of halothane is shifted by 250-300 mV to more negative
      potentials at an eppg electrode than that observed at the GC-CNT electrode.
      Therefore the results of this investigation show that, surprisingly, the
      electrocatalysis is not solely due to the introduction of edge-plane-like defect
      sites on the carbon nanotubes as is commonly found for many other substrates
      showing favourable voltammetry at nanotube modified electrodes. Instead, we
      reveal that in this unusual case the electroactive sites for the reduction of
      halothane are due to the presence of copper nanoparticles occluded within the
      carbon nanotubes during their production, which are never completely removed by
      standard purification techniques such as acid washing. This is only the third
      known case where apparent electrocatalysis by carbon nanotube modified electrodes
      is due to occluded metal-related nanoparticles within the nanotube structure,
      rather than the active sites being the edge-plane-like defect sites on the
      nanotubes. Furthermore this is the first case where the active sites are
      nanoparticles of copper metal, rather than metal oxide nanoparticles (namely
      oxides of iron(II)/(III)) as was found to be the case in the previous examples.

PMID- 17028722
TI  - Selective coulometric release of ions from ion selective polymeric membranes for
      calibration-free titrations.
AB  - Coulometry belongs to one of the few known calibration-free techniques and is
      therefore highly attractive for chemical analysis. Titrations performed by the
      coulometric generation of reactants is a well-known approach in electrochemistry,
      but suffers from limited selectivity and is therefore not generally suited for
      samples of varying or unknown composition. Here, the selective coulometric
      release of ionic reagents from ion-selective polymeric membrane materials
      ordinarily used for the fabrication of ion-selective electrodes is described. The
      selectivity of such membranes can be tuned to a significant extent by the type
      and concentration of ionophore and lipophilic ion-exchanger and is today well
      understood. An anodic current of fixed magnitude and duration may be imposed
      across such a membrane to release a defined quantity of ions with high
      selectivity and precision. Since the applied current relates to a defined ion
      flux, a variety of non-redox active ions may be accurately released with this
      technique. In this work, the released titrant's activity was measured with a
      second ionophore-based ion-selective electrode and corresponded well with
      expected dosage levels on the basis of Faraday's law of electrolysis. Initial
      examples of coulometric titrations explored here include the release of calcium
      ions for complexometric titrations, including back titrations, and the release of
      barium ions to determine sulfate.

PMID- 17028724
TI  - An electronic DNA microarray technique for detection and differentiation of
      viable Campylobacter species.
AB  - An electronic oligonucleotide microarray technique was developed for detection
      and differentiation of the viable Campylobacter species, C. jejuni, C. coli, and
      C. lari. This development consisted of four major components: identification of
      single nucleotide polymorphisms (SNPs) within the hsp60 gene as species markers,
      design of fluorescently labelled SNP-based reporters, development of an
      electronic microarray detection, and application of the integrated technique to
      analysis of Campylobacter species in food samples. A unique capability of this
      technique is the specific detection of viable cells and not dead ones. This is
      achieved by using mRNA of the 60 kDa heat-shock protein as the viability marker.
      The identification of two unique SNPs closely located at positions 291 and 294 of
      the hsp60 gene enabled the differentiation of the three Campylobacter species.
      This technique was able to detect as few as two viable Campylobacter cells. The
      analysis of 19 blind Campylobacter samples showed 100% agreement with their
      identities obtained using pulsed-field gel electrophoresis. The analysis of six
      chicken samples revealed the presence of C. coli in one of the samples.

PMID- 17028725
TI  - A compact broadband cavity enhanced absorption spectrometer for detection of
      atmospheric NO(2) using light emitting diodes.
AB  - A compact and low power detector has been developed for the in situ measurement
      of atmospheric NO(2) using broadband cavity enhanced absorption spectroscopy.
      Absorption by the O(2)-O(2) collisional pair was used to determine the cavity
      mirror reflectivity, thus enabling the retrieval of absolute absorber
      concentrations by differential spectral fitting techniques. Quantitative amounts
      of ambient NO(2) (between 3 and 32 parts per billion) were retrieved from spectra
      recorded in the presence of ambient aerosol with statistical uncertainties
      approaching 100 ppt for a 60 s averaging period. The instrument's response was
      compared to that of a commercial chemiluminescence detector and was found to
      agree to within 6%.

PMID- 17028726
TI  - Subfemtomolar electrochemical detection of target DNA by catalytic enlargement of
      the hybridized gold nanoparticle labels.
AB  - After showing the failure of conventional gold-enhancement procedures to amplify
      the gold nanoparticle-based electrochemical transduction of DNA hybridization in
      polystyrene microwells, a new efficient protocol was developed and evaluated for
      the sensitive quantification of a 35 base-pair human cytomegalovirus nucleic acid
      target (tDNA). In this assay, the hybridization of the target adsorbed on the
      bottom of microwells with an oligonucleotide-modified Au nanoparticle detection
      probe (pDNA-Au) was monitored by the anodic stripping detection of the chemically
      oxidized gold label at a screen-printed microband electrode (SPMBE). Thanks to
      the combination of the sensitive Au(III) determination at a SPMBE with the large
      amount of Au(III) released from each pDNA-Au, picomolar detection limits of tDNA
      can be achieved. Further enhancement of the hybridization signal based on the
      autocatalytic reductive deposition of ionic gold (Au(III)) on the surface of the
      gold nanoparticle labels anchored on the hybrids was first envisaged by
      incubating the commonly used mixture of Au(III) and hydroxylamine (NH(2)OH).
      However, due to a considerable nonspecific current response of poor
      reproducibility it was not possible to significantly improve the analytical
      performances of the method under these conditions. Complementary transmission
      electronic microscopy experiments indicated the loss of most of the grown gold
      labels during the post-enlargement rinsing step. To circumvent this drawback, a
      polymeric solute containing polyethyleneglycol and sodium chloride was introduced
      in the growth media to act as an aggregating agent during the catalytic process
      and thus retain the enlarged labels on the bottom of the microwell. This
      strategy, which led to an efficient increase of the hybridization response,
      allowed detection of tDNA concentrations as low as 600 aM (i.e., 10(4) lower than
      without amplification), and thus offers great promise for ultrasensitive
      detection of other hybridization events.

PMID- 17028727
TI  - Use of microchip-based hydrodynamic focusing to measure the deformation-induced
      release of ATP from erythrocytes.
AB  - In order to understand the role that erythrocytes play in conditions such as
      pulmonary hypertension, in vitro mimics of the microcirculation are needed. This
      paper describes the use of microchip-based hydrodynamic focusing to develop a
      mimic that allows both mechanical deformation of erythrocytes and quantification
      of the adenosine triphosphate (ATP) that is subsequently released in response to
      this deformation. In this mimic, two sheathing streams of a luciferin/luciferase
      mixture are used to focus and deform a central fluid flow of an erythrocyte
      sample. The focusing width is changed by simply manipulating the sheath flow
      rate. This allows a variety of cross-sectional areas to be studied using single
      point chemiluminescent detection. It was shown that increasing the sheath flow
      rate does result in elevated levels of ATP release. For example, one sample of
      rabbit erythrocytes released 0.80 (+/- 0.13) microM ATP when focused to a cross
      section of 3480 microm(2), while focusing the same sample to a smaller cross
      section (1160 microm(2)) led to a release of 6.43 (+/- 0.40) microM ATP. In
      addition, two different inhibitors, diamide and glibenclamide, were used to
      ensure a lack of cell lysis. This approach can be used to examine a wide range of
      deformation forces in a high throughput fashion and will be of interest to
      researchers studying the mechanisms leading to vasodilation in the
      microvasculature.

PMID- 17028728
TI  - Novel integrated paired emitter-detector diode (PEDD) as a miniaturized
      photometric detector in HPLC.
AB  - A novel low power, low cost, highly sensitive, miniaturized light emitting diode
      (LED) based flow detector has been used as optical detector for the detection of
      sample components in high performance liquid chromatography (HPLC). This
      colorimetric detector employs two LEDs, one operating in normal mode as a light
      source and the other is reverse biased to work as a light detector. Instead of
      measuring the photocurrent directly, a simple timer circuit is used to measure
      the time taken for the photocurrent generated by the emitter LED (lambda(max) 500
      nm) to discharge the detector LED (lambda(max) 621 nm) from 5 V (logic 1) to 1.7
      V (logic 0) to give digital output directly without using an A/D converter.
      Employing a post-column reagent method, a Nucleosil 100-7 column (functionalized
      with iminodiacetic acid (IDA) groups) was used to separate a mixture of
      transition metal complexes, manganese(II) and cobalt(II) in 4-(2-pyridylazo)
      resorcinol (PAR). All optical measurements were taken by using both the in-built
      HPLC variable wavelength detector and the proposed paired-emitter-detector-diode
      (PEDD) optical detector configured in-line for data comparison. The concentration
      range investigated using the PEDD was found to give a linear response to the
      Mn(II) and Co(II) PAR complexes. The effects of flow rate and emitter LED light
      source intensity were investigated. Under optimised conditions the PEDD detector
      offered a linear range of 0.9-100 microM and LOD of 0.09 microM for Mn-PAR
      complex. A linear range of 0.2-100 microM and LOD of 0.09 microM for Co-PAR
      complex was achieved.

PMID- 17028729
TI  - Rapid electrophoretic separations in short capillaries using contactless
      conductivity detection and a sequential injection analysis manifold for
      hydrodynamic sample loading.
AB  - A sequential injection-capillary electrophoresis (SI-CE) system for the fast and
      automated quantitative analysis of anions and cations is described. Because of
      the low sample load in capillary electrophoresis a split injection approach had
      to be used to achieve reliable hydrodynamic injection. The use of a capillary of
      8 cm effective length allowed for the separation of five inorganic cations within
      11 s. One common electrolyte solution containing 12 mM l-histidine and 2 mM 18
      crown-6 whose pH value was adjusted to 4.0 with 10% v/v acetic acid was used for
      anions and cations, thus the analysis of both groups of analytes could be carried
      out in rapid sequence simply by switching the polarity of the high voltage
      supply. The system also allows automated flushing of the capillary. Detection
      limits between about 2 and 5 micromol l(-1) could be achieved with the
      contactless conductivity detector employed.

PMID- 17028730
TI  - Template-free routes to porous inorganic materials.
AB  - New approaches to solid-state reactivity have allowed us to develop unusual
      routes to porous inorganic materials. This article describes our recent work on
      template-free routes involving the selective leaching of one phase from a two
      phase composite to form porous oxides. Subsequent reactions have been developed
      to yield porous metals, conformal coatings, and hierarchically porous materials.
      Pores can also be generated through simple redox processes in transition-metal
      oxides; such redox cycling allows mesopores to be produced in a regenerative
      process in a material which is already macroporous.

PMID- 17028731
TI  - Two new 3D metal-organic frameworks of nanoscale cages constructed by Cd(II) and
      conformationally-flexible cyclohexanehexacarboxylate.
AB  - Hydrothermal reactions of Cd(NO3)2.4H2O with a,e,a,e,a,e-1,2,3,4,5,6
      cyclohexanehexacarboxylic acid (H6L(I)) generate two new 3D MOFs with nanoscale
      cages, in which the L(I) ligand in the first MOF transforms its conformation to
      the e,e,e,e,e,e form while the L(I) ligand in the second MOF transforms its
      conformation to mixed e,e,e,e,e,e and e,e,e,e,a,a forms in a 1 : 3 ratio, showing
      the effect of the auxiliary sodium ion on stabilizing the intermediate
      conformations and on the construction of the heterometallic MOF structure.

PMID- 17028732
TI  - Chiral polymers by iterative tandem catalysis.
AB  - Racemic omega-substituted caprolactones can be completely converted into chiral
      polyesters of remarkable MW and high ee by combining lipase-catalyzed ring
      opening polymerization with Ru-catalyzed racemization.

PMID- 17028733
TI  - A lanthanide metal-organic framework with high thermal stability and available
      Lewis-acid metal sites.
AB  - A lanthanide metal-organic framework, Dy(BTC)(H2O).DMF, with excellent thermal
      stability shows a high surface area, 655 m(2) g(-1), high hydrogen and carbon
      dioxide storage capability, and available Lewis-acid metal sites which could be
      anticipated to use in catalysis and metal-site specific chemical sensor.

PMID- 17028734
TI  - Metal-mediated coordination polymer nanotubes of 5,10,15,20-tetrapyridylporphine
      and tris(4-pyridyl)-1,3,5-triazine at the water-chloroform interface.
AB  - Coordination polymer nanotubes have been prepared by using the Hg2+-mediated co
      assembly of two ligands, tetrapyridylporphine (TPyP) and tris(4-pyridyl)-1,3,5
      triazine (TPyTa), at the water-chloroform interface.

PMID- 17028735
TI  - Unique gold chemoselectivity for the aerobic oxidation of allylic alcohols.
AB  - Gold nanoparticles supported on nanocrystalline ceria has been found to be more
      active and chemoselective than palladium and gold(core)-palladium(shell)
      nanoparticles for the aerobic oxidation of allylic alcohols.

PMID- 17028736
TI  - Tetranuclear Cu(II) complex supported by a central mu4-1,1,3,3 azide bridge.
AB  - The new cluster [Cu4L2(N3)]Cl.16H2O has been synthesized and characterized; it
      features a unique mu4-1,1,3,3 bridging mode for azide, whose capacity to mediate
      magnetic coupling has been examined through bulk magnetic measurements and
      numeric fitting procedures.

PMID- 17028737
TI  - Easy access to stable pentavalent uranyl complexes.
AB  - Reaction of UO2I2(THF)3 with 1 molar equivalent of KC5R5 (R = H, Me) in pyridine
      led to the uranyl(V) compound {[UO2(Py)5][KI2(Py)2]}(infinity), which is an
      infinite 1D polymer in its crystalline form; the UO2X(THF)n (X = I, OSO2CF3)
      complexes were obtained by reduction of their U(VI) parents with TlC5H5 or KC5R5
      in THF.

PMID- 17028738
TI  - Rhodium-catalyzed carbonylative arylation of alkynes with arylboronic acids: an
      efficient and straightforward method in the synthesis of 5-aryl-2(5H)-furanones.
AB  - 5-Aryl-2(5H)-furanones can be synthesized by the Rh-catalyzed reactions of
      arylboronic acids with internal alkynes under a CO atmosphere.

PMID- 17028739
TI  - The intramolecular beta-fluorine...ammonium interaction in 4- and 8-membered
      rings.
AB  - The structures of 3-fluoroazetidinium hydrochloride and 3-fluoro-1,5
      diazacyclooctane hydrobromide are explored both by X-ray diffraction analysis and
      DFT calculations, and the conformations of these molecules are shown to be
      significantly influenced by the through space C-F...N+ interaction.

PMID- 17028740
TI  - The chemical modification of liposome surfaces via a copper-mediated [3 + 2]
      azide-alkyne cycloaddition monitored by a colorimetric assay.
AB  - A generic method for the efficient in-situ modification of liposomes is described
      based on "click" chemistry, and a simple colorimetric assay is developed for
      monitoring the reaction.

PMID- 17028741
TI  - Formation of triple helical nanofibers using self-assembling chiral benzene-1,3,5
      tricarboxamides and reversal of the nanostructure's handedness using mirror image
      building blocks.
AB  - Intertwining triple helical nanofibers with an overall handedness have been
      formed from self-assembling chiral benzene-1,3,5-tricarboxamides , and , whereas
      the achiral benzene-1,3,5-tricarboxamide upon self-association gives rise to
      straight nanofibers without any twist and transmission electron microscopy images
      of chiral compounds clearly demonstrate that the handedness of the triple helical
      nanofibers can be reversed by using the enantiomeric benzene-1,3,5-tricarboxamide
      building blocks.

PMID- 17028742
TI  - Anion binding inhibition of the formation of a helical organogel.
AB  - A chiral tris(urea) organogelator gels dmso-water and methanol-water mixtures at
      low weight percent. The formation of the helical gel fibres is partially
      inhibited by addition of chloride, which is bound by the gelator, resulting in
      fully crystalline material characterised by X-ray crystallography.

PMID- 17028743
TI  - Tuning electron transfer through p-phenyleneethynylene molecular wires.
AB  - Weak wire-like behavior-with a damping factor (beta) of 0.2 +/- 0.05 A(-1)--has
      been found in a series of C60-wire-exTTF systems (i.e., p-phenyleneethynylene):
      these results contrast with previous observations involving p-phenylenevinylene
      systems.

PMID- 17028744
TI  - Ultrasensitive detection of DNA by the PCR-Induced generation of DNAzymes: the
      DNAzyme primer approach.
AB  - The ultrasensitive detection of DNA is achieved by PCR-induced evolution of a
      DNAzyme.

PMID- 17028745
TI  - New reactivity and structural insights of alkali-metal-mediated alumination in
      directed ortho-alumination of a tertiary aromatic amide.
AB  - The first reported sodium alkyl(TMP)aluminate reagent to be synthesised and
      crystallographically characterised, [TMEDA.Na(mu-TMP)(mu-(I)Bu)Al((I)Bu)2],
      reacts as an amido base towards phenylacetylene to form crystalline
      [(TMEDA)2.Na(mu-CCPh)(mu-(I)Bu)Al((I)Bu)2]; whereas the congeneric TMEDA
      stabilised lithium (TMP)aluminate exhibits dual alkyl/amido basicity in its
      reaction with N,N-diisopropylbenzamide to form a novel heterobimetallic
      heterotrianionic crystalline complex [{PhC(=O)N(iPr)2}.Li{2-[1
      C(=O)N(iPr)2]C6H4}{Me2NCH2CH2N(Me)CH2}Al(iBu)2], which, in addition to having an
      ortho-deprotonated benzamide ligand, also contains a methyl-deprotonated TMEDA
      ligand and a neutral benzamide molecule ligated to lithium.

PMID- 17028746
TI  - A highly selective, organocatalytic route to chiral 1,2-oxazines from ketones.
AB  - A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines
      from achiral ketone starting materials is reported, which proceeds in moderate to
      good yields and excellent enantioselectivity.

PMID- 17028747
TI  - Accessing tetrahydrofuran-based natural products by microbial Baeyer-Villiger
      biooxidation.
AB  - A heterobicyclic lactone obtained by stereoselective Baeyer-Villiger biooxidation
      with recombinant whole-cells expressing cyclopentanone monooxygenase from
      Comamonas sp. NCIMB 9872 was used for formal total syntheses of various natural
      products containing a tetrahydrofuran structural motif.

PMID- 17028748
TI  - Molecularly-imprinted polymeric logic gates selective for predetermined chemical
      input species.
AB  - Selective AND and OR logic gates were fabricated by molecular imprinting with
      simultaneous use of two kinds of template species, with the resultant binding
      behaviour (AND or OR) of the imprinted polymers governed by intermolecular
      interactions between the two template species.

PMID- 17028749
TI  - Multilayer films based on host-guest interactions between biocompatible polymers.
AB  - Multilayer films are formed using host-guest interaction between two derivatized
      chitosans, one, with beta-cyclodextrin cavities and the other with adamantyl
      moieties.

PMID- 17028750
TI  - Site-specific transition of cytosine to uracil via reversible DNA photoligation.
AB  - We report that deamination coupled with 5-carboxyvinyldeoxyuridine-mediated
      photobranching causes the heat-induced transition of cytosine to uracil with high
      efficiency without any side reaction.

PMID- 17028751
TI  - 3-Hydroxypyrrolidines from epoxysulfonamides and dimethylsulfoxonium methylide.
AB  - N-Tosyl-protected 3-hydroxypyrrolidines are prepared by reaction of
      dimethylsulfoxonium methylide with readily available epoxysulfonamides.

PMID- 17028752
TI  - Selection of DNA ligands for protein kinase C-delta.
AB  - Protein kinase Cs are a family of serine and threonine kinases that mediate a
      wide variety of cellular signalling processes such as cell growth,
      differentiation, apoptosis and tumor development. We have selected high-affinity
      DNA aptamers for PKCdelta by capillary electrophoresis based SELEX (systematic
      evolution of ligands by exponential enrichment, CE-SELEX). We have demonstrated
      that fluorescently tagged PB9 aptamer can specifically recognize PKCdelta under
      in vitro conditions. The Kd of the aptamer-protein binding is 122 nM. These
      aptamers will enable us to apply fluorescently labelled probes to study the
      spatiotemporal dynamics and activation of individual endogenous PKC isoforms
      during various cell signalling processes.

PMID- 17028753
TI  - An outstanding catalyst for asymmetric transfer hydrogenation in aqueous solution
      and formic acid/triethylamine.
AB  - A Rh/tetramethylcyclopentadienyl complex containing a tethered functionality has
      been demonstrated to give excellent results in the asymmetric transfer
      hydrogenation of ketones in both aqueous and formic acid/triethylamine media.

PMID- 17028754
TI  - Addressing the regioselectivity problem in organic synthesis.
AB  - A screening process uncovered a heterogeneous catalytic system that hydrolyzes
      one of two nearly identical ketals in several diketals with a high selectivity.

PMID- 17028755
TI  - A new and convenient method for the synthesis of strong non-ionic bases.
AB  - Various strong non-ionic phosphazene bases were obtained by a new, efficient and
      very simple method involving the lithium phosphonium azayldiide Ph3P=NLi as a
      precursor.

PMID- 17028756
TI  - Discrete copper(I) clusters with Cu6P6Se6 and Cu6P4Se6 cores.
AB  - The reactions of chalcogenophosphinites with copper(I) metal salts are shown to
      yield highly stable, multi-metallic copper-chalcogen based clusters with novel
      topologies.

PMID- 17028757
TI  - Synthesis of the ester side chains of some potently antileukemic harringtonia
      alkaloids from chiral citrates.
AB  - The selective reduction of one of the three carboxyl groups of two chiral citric
      acid derivatives to the corresponding aldehydes, under Rosenmund conditions, are
      reported together with the application of these aldehydes to the syntheses of the
      ester side chains of some potently antileukemic Cephalotaxus alkaloids e.g.
      anhydroharringtonine.

PMID- 17028758
TI  - A transmembrane anion transporter selective for nitrate over chloride.
AB  - The C3-symmetric triamide selectively transports NO3- anions across lipid
      vesicles: this H+-NO3- co-transporter alters the pH inside of liposomes
      experiencing a NO3-/Cl- gradient.

PMID- 17028759
TI  - Pallado-catalysed hydrophosphination of alkynes: access to enantio-enriched P
      stereogenic vinyl phosphine-boranes.
AB  - Preliminary results dealing with the synthesis of non-racemic P-stereogenic
      vinylphosphine-boranes by hydrophosphination of alkynes in the presence of a
      chiral catalyst are reported.

PMID- 17028760
TI  - Kinetic and thermodynamic parameters for the equilibrium reactions of phenols
      with the dpph. radical.
AB  - The kinetics and energetics of the reversible reaction of phenols with the dpph.
      radical have been studied; steric shielding of the divalent N by the o-NO2 in
      dpph. seems to be the main cause of the entropic barriers of this reaction.

PMID- 17028761
TI  - Sodium intake in very low birth weight infants: is more always better?

PMID- 17028762
TI  - The Latin American exception: why is childhood asthma so prevalent in Brazil?

PMID- 17028763
TI  - We need to predict extubation failure.

PMID- 17028764
TI  - Cockroach allergy: risk factor for asthma severity.

PMID- 17028766
TI  - Serum prevalence of celiac disease in children and adolescents with type 1
      diabetes mellitus.

PMID- 17028768
TI  - Pediatrics - research and publications.

PMID- 17028769
TI  - Antimicrobial properties of alpha-MSH and related synthetic melanocortins.
AB  - The natural antimicrobial peptides are ancient host defense effector molecules,
      present in organisms across the evolutionary spectrum. Several properties of
      alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a
      natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared
      during the Paleozoic era, long before adaptive immunity developed and, like
      natural antimicrobial molecules, is produced by barrier epithelia, immunocytes,
      and within the central nervous system. alpha-MSH was discovered to have
      antimicrobial activity against two representative pathogens, Staphylococcus
      aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to
      be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP
      inducing capacity of alpha-MSH likely interferes with the yeast's own regulatory
      mechanisms of this essential signaling pathway. It is remarkable that this
      mechanism of action in yeast mimics the influences of alpha-MSH in mammalian
      cells in which the peptide binds to G-protein-linked melanocortin receptors,
      activates adenylyl cyclase, and increases cAMP. When considering that most of the
      natural antimicrobial peptides enhance the local inflammatory reaction, the anti
      inflammatory and antipyretic effects of alpha-MSH confer unique properties to
      this molecule relative to other natural antimicrobial molecules. Synthetic
      derivatives, chemically stable and resistant to enzymatic degradation, could form
      the basis for novel therapies that combine anti-inflammatory and antimicrobial
      properties.

PMID- 17028770
TI  - Accuracy of the combination of mammography and sonography in predicting tumor
      response in breast cancer patients after neoadjuvant chemotherapy.
AB  - BACKGROUND: Residual tumor size after neoadjuvant chemotherapy is an important
      consideration in surgical planning. We examined the accuracy of the combination
      of mammography and sonography in predicting pathologic residual tumor size.
      METHODS: Tumor size was evaluated by physical examination, mammography, and
      sonography at diagnosis and before surgery in 162 breast cancer patients who
      received neoadjuvant chemotherapy. Agreement between the predicted and the
      pathologic responses and the predicted and the pathologic tumor sizes was
      calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone
      receptor positivity, and the presence of an extensive intraductal component on
      the accuracy of mammography and sonography in predicting pathologic residual
      tumor size was analyzed. RESULTS: Forty-two patients (25.9%) had a pathologic
      complete response (pCR). Overall agreement between predicted and pathologic
      responses was 53% for physical examination, 67% for mammography plus sonography,
      and 63% for physical examination plus mammography and sonography. The sensitivity
      of mammography and sonography in predicting pCR was 78.6%, and the specificity
      was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography
      and sonography correlated with pathologic residual tumor size (r = .662);
      pathologic tumor size was within .5 cm of predicted in 69.1% of patients.
      Multivariate analysis showed that pathologic residual tumor size was
      underestimated for lobular carcinoma and overestimated for poorly differentiated
      tumors. CONCLUSIONS: The combination of mammography and sonography has a high
      accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual
      tumor size in mammography and sonography with pathologic residual tumor size was
      moderate.

PMID- 17028771
TI  - Surgical management of symptomatic pericardial effusion in patients with solid
      malignancies.
AB  - BACKGROUND: Symptomatic pericardial effusion in patients with cancer may lead to
      a life-threatening event that requires diligent treatment, but the best surgical
      treatment is still controversial. The purpose of this study was to identify
      predictors of survival for patients with solid malignancies and symptomatic
      pericardial effusion, which might help to select the best surgical treatment for
      each patient. METHODS: We retrospectively analyzed 47 patients with solid
      malignancies concomitant with symptomatic pericardial effusion who underwent
      surgery between 1994 and 2004. Overall survival was calculated from date of
      surgery, and prognostic importance of clinical and pathological variables was
      assessed. RESULTS: The most common primary sites of disease were breast (46.8%)
      and lung (25.6%). Initial pericardiocentesis were performed in 29 patients;
      median volume of fluid drained was 480 mL. Median interval from the diagnosis of
      primary cancer to the development of pericardial effusion (pericardial effusion
      free interval) was 34.8 months. Definitive surgical treatment was performed in 43
      patients, as follows: subxiphoid pericardial window (n = 21); thoracotomy and
      pleuropericardial window (n = 10); pericardiodesis (n = 8); and
      videothoracoscopic pleuropericardial window (n = 4). Pericardiocentesis was the
      only procedure in four patients. Median follow-up was 2.9 months. Median overall
      survival was 3.7 months. Pericardial effusion-free interval longer than 35 months
      and more than 480 mL of fluid drained at initial pericardiocentesis were
      determinants of better survival. CONCLUSIONS: Pericardial window and
      pericardiodesis seem to be safe and efficacious in treating effusion of the
      pericardium. Pericardial effusion-free interval and volume drained at initial
      pericardiocentesis are determinants of outcome.

PMID- 17028772
TI  - Risk factors for non-sentinel lymph node metastases in patients with breast
      cancer. The outcome of a multi-institutional study.
AB  - BACKGROUND: In this multi-institutional prospective study, we evaluated whether
      we could identify risk factors predictive for non-sentinel lymph node (non-SN)
      metastases in breast cancer patients with a positive sentinel lymph node (SN).
      METHODS: In this multi-institutional study, 541 eligible breast cancer patients
      were included prospectively. RESULTS: The occurrence of non-SN metastases was
      related to the size of the SN metastasis (P = .02), primary tumor size (P =
      .001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for
      SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro
      metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared
      with </=3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were
      no positive non-SNs when the primary tumor size was </=1.0 cm (n = 24) [95%
      confidence interval (95% CI) 0%-14.0%]. The proportion of positive non-SNs ranged
      in a prognostic logistic regression model from 9.7% (95% CI 4.0%-23.0%) for
      patients with SN isolated tumor cells, tumor size of 1.1-3.0 cm, and without
      vessel invasion, to 72.6% (95% CI 47.0%-89.0%) for patients with SN macro
      metastasis, tumor size >3.0 cm, and with vessel invasion. CONCLUSION: We
      identified three predictive factors for non-SN metastases in breast cancer
      patients with a positive SN: size of the SN metastasis; primary tumor size; and
      vessel invasion. We were not able to identify a specific group of patients with a
      positive SN in whom the risk for non-SN metastases was less than 5%.

PMID- 17028773
TI  - Health care students' differing conceptions of expertise: a challenge for inter
      professional care.
AB  - The aim of the study was to examine do health care students, who study at
      different programs, value similar expert qualities. To investigate this issue, a
      questionnaire was administered among health care students in a Finnish
      polytechnic (two cohorts, total n = 466), consisting of a scale for rating the
      importance of different expert qualities. The questionnaire resulted in the
      following dimensions of the conceptions of expertise: (1) social skills, (2)
      scientific skills, (3) innovativeness, (4) continuing self-development, and (5)
      problem-solving skills. Also the Inventory of General Study Orientations (IGSO)
      was applied to analyse possible motivational explanations for different
      conceptions of expertise. In addition to the scales, an open-ended writing task
      was used to explore in depth students' conceptions of expertise. It appeared that
      study orientations were a minor factor in the study, while study environment
      (study programs) clearly differentiated students' conceptions of expertise. Thus,
      the study argues that health care students' conceptions of expertise are
      constituted mainly on domain-specific bases and that students who graduate from
      different programs may possess very diverse ideas about their profession.
      Consequently, different conceptions captured during the education form a major
      challenge for inter-professional care later in work-life. This phenomenon should
      be taken into account when organising health care education.

PMID- 17028774
TI  - Recombinant expression of human cathelicidin (hCAP18/LL-37) in Pichia pastoris.
AB  - The constitutive expression of human cathelicidin LL-37 antimicrobial peptide was
      achieved using the methylotrophic yeast, Pichia pastoris. An LL-37 cDNA clone was
      amplified by PCR using human fetal cDNA library as template. The 111 bp fragment
      encoding mature LL-37 gene was subcloned into pGAPZ-E, an episomal form of the
      pGAPZB vector incorporating PARS1. It was then transformed into the P. pastoris X
      33 strain for intracellular expression. A small peptide with a molecular mass of
      about 5 kDa was detected by 17% peptide-PAGE analysis. The recombinant LL-37
      peptide was purified from the gel and its amino acid sequence was determined by
      LC-ESI-MS/MS analysis. The initiating amino acid, methionine, was still attached
      to the N-terminal region of recombinant LL-37. LL-37 crude extract from P.
      pastoris showed an antimicrobial activity against Micrococcus luteus as the test
      strain. The successful expression of human LL-37 indicates that the system may be
      applicable to the expression of other human defensins without resorting to fusion
      protein constructions.

PMID- 17028775
TI  - Effect of pretreatment chemicals on xylose fermentation by Pichia stipitis.
AB  - Pretreatment of biomass with dilute H2SO4 results in residual acid which is
      neutralized with alkalis such as Ca(OH)2, NaOH and NH4OH. The salt produced after
      neutralization has an effect on the fermentation of Pichia stipitis. Synthetic
      media of xylose (60 g total sugar/l) was fermented to ethanol in the presence and
      absence of the salts using P. stipitis CBS 6054. CaSO4 enhanced growth and
      xylitol production, but produced the lowest ethanol concentration and yield after
      140 h. Na2SO4 inhibited xylitol production, slightly enhanced growth towards the
      end of fermentation but had no significant effect on xylose consumption and
      ethanol concentration. (NH4)2SO4 inhibited growth, had no effect on xylitol
      production, and enhanced xylose consumption and ethanol production.

PMID- 17028776
TI  - Cancer/testis antigen cancer-associated gene (CAGE) promotes motility of cancer
      cells through activation of focal adhesion kinase (FAK).
AB  - The cancer-associated gene (CAGE) is a novel cancer/testis antigen. Over
      expression of it increased phosphorylation of focal adhesion kinase (FAK) and
      enhanced motility of SNU387 cells. Focal adhesion, kinase-related non-kinase
      (FRNK), an endogenous inhibitor of FAK, was significantly suppressed. This
      suggests that CAGE-promoted motility requires FAK. The inhibition of Rho
      Associated coiled-coil-containing protein kinase (ROCK), an activator of FAK,
      also suppressed CAGE-promoted motility.

PMID- 17028777
TI  - Metabolic characterisation of E. coli citrate synthase and phosphoenolpyruvate
      carboxylase mutants in aerobic cultures.
AB  - E. coli is still one of the most commonly used hosts for protein production.
      However, when it is grown with excess glucose, acetate accumulation occurs.
      Elevated acetate concentrations have an inhibitory effect on growth rate and
      recombinant protein yield, and thus elimination of acetate formation is an
      important aim towards industrial production of recombinant proteins. Here we
      examine if over-expression of citrate synthase (gltA) or phosphoenolpyruvate
      carboxylase (ppc) can eliminate acetate production. Knock-out as well as over
      expression mutants were constructed and characterized. Knocking out ppc or gltA
      decreased the maximum cell density by 14% and increased the acetate excretion by
      7%, respectively decreased it by 10%. Over-expression of ppc or gltA increased
      the maximum cell dry weight by 91% and 23%, respectively. No acetate excretion
      was detected at these increased cell densities (35 and 23 g/l, respectively).

PMID- 17028778
TI  - Pretreatment of lipase with soybean oil before immobilization to prevent loss of
      activity.
AB  - Lipase was pretreated with soybean oil in order to allow fatty acids to bond to
      the active site before immobilization. This pretreated lipase exhibited steric
      hindrance around the active site such that during immobilization, covalent bonds
      were formed between the carrier and the lipase region far from the active site.
      The activity of the pretreated lipase immobilized covalently on a silica gel was
      530 U/g-matrix, which is 16 times higher than that of the immobilized non
      pretreated lipase. In addition, the immobilized lipase activity was maintained at
      levels exceeding 90% of its original activity after 10 reuses.

PMID- 17028779
TI  - IgE binding to proteins from sesame and assessment of allergenicity: implications
      for biotechnology?
AB  - Successful prediction of the potential allergenicity of a protein may be a key
      factor in the development of novel, genetically modified foods. The use of the
      decision tree approach for the prediction of allergenicity is discussed. The
      methods currently used for identifying allergenic proteins (including use of IgE
      from patient sera for recognition of proteins) are reviewed. Finally, a specific
      review of the literature concerning identification of allergens from sesame leads
      to the conclusion that in the absence of validated animal models, identification
      of allergenicity (and, consequently, prediction of allergenicity) may be
      problematic.

PMID- 17028780
TI  - Involvement of polyamines in plant response to abiotic stress.
AB  - Environmental stresses are the major cause of crop loss worldwide. Polyamines are
      involved in plant stress responses. However, the precise role(s) of polyamine
      metabolism in these processes remain ill-defined. Transgenic approaches
      demonstrate that polyamines play essential roles in stress tolerance and open up
      the possibility to exploit this strategy to improve plant tolerance to multiple
      environmental stresses. The use of Arabidopsis as a model plant enables us to
      carry out global expression studies of the polyamine metabolic genes under
      different stress conditions, as well as genome-wide expression analyses of
      insertional-mutants and plants over-expressing these genes. These studies are
      essential to dissect the polyamine mechanism of action in order to design new
      strategies to increase plant survival in adverse environments.

PMID- 17028781
TI  - Cloning and characterization of a novel small monomeric GTPase, RasL10B, with
      tumor suppressor potential.
AB  - Ras proteins are members of the superfamily of small GTPase. A novel human Ras
      like transcript, termed RasL10B, was isolated from human blood cell cDNA library.
      RasL10B gene contains four exons and three introns, which encodes a 203 amino
      acid protein with a molecular mass of about 23.2 kDa. RT-PCR analysis showed that
      RasL10B is expressed extensively in human tissues. Subcellular location analysis
      of GFP-RasL10B fusion protein revealed that RasL10B was distributed to the
      cytoplasm of COS7 cells. In addition, RasL10B was expressed in E. coli Rosette
      (DE3) and purified to a homogenicity by Ni-NTA affinity chromatography. Finally,
      the mRNA levels of RasL10B were down-regulated in all human breast cancer cell
      lines we tested. In summary, RasL10B is a new member of Ras superfamily with
      tumor suppressor potential.

PMID- 17028782
TI  - Enzymatic synthesis of (R)-cyanohydrins by a novel (R)-oxynitrilase from Vicia
      sativa L.
AB  - The defatted seed meal of common vetch (Vicia sativa L.) served as a source of
      (R)-oxynitrilase which catalyzed the enantioselective addition of HCN to
      aromatic, heteroaromatic, fluoro-substituted aromatic aldehydes to produce the
      corresponding enantiomeric pure cyanohydrins in yields of 52-100% and 88-99% ee
      at 12 degrees C under micro-aqueous medium (diisopropyl ether) without addition
      of buffer solution.

PMID- 17028783
TI  - Cloning, expression, and characterization of a glycoside hydrolase family 50 beta
      agarase from a marine Agarivorans isolate.
AB  - The gene for a thermostable beta-agarase from Agarivorans sp. JA-1 was cloned and
      sequenced. It comprised an open reading frame of 2,988 base pairs, which encode a
      protein of 109,450 daltons consisting of 995 amino acid residues. A comparison of
      the entire sequence showed that the enzyme has 98.8% sequence similarities to
      beta-agarase from Vibrio sp. JT1070, indicating that it belongs to the family
      glycoside hydrolase (GH)-50. The gene corresponding to a mature protein of 976
      amino acids was inserted and expressed in Escherichia coli. The recombinant beta
      agarase was purified to homogeneity. It had maximal activity at 40 degrees C and
      pH 8.0 in the presence of 1 mM NaCl and 1 mM CaCl(2). The enzyme hydrolyzed
      agarose as well as neoagarohexaose and neoagarotetraose to yield neoagarobiose as
      the main product. Thus, the enzyme would be useful for the industrial production
      of neoagarobiose.

PMID- 17028784
TI  - Transgenic mice can express mutant human coagulation factor IX with higher level
      of clotting activity.
AB  - To improve the available values of transgenic animals, we produced a mutant human
      coagulation factor IX minigene (including cDNA and intron I) with arginine at 338
      changed to alanine (R338A-hFIX) by using a direct mutation technique. The R338A
      hFIX minigene was then cloned into a plasmid carrying the goat beta-casein
      promoter to get a mammary gland-specific expression vector. The clotting activity
      in the supernatant of the transfected HC-11 cells increased to approximately
      three times more than that of wild-type hFIX. Nine transgenic mice (three females
      and six males) were produced, and the copy number of the foreign gene was very
      different, ranging from 1 to 43 in different lines. ELISA, Western blot, and
      clotting assay experiments showed that the transgenic mice could express R338A
      hFIX, showing higher average levels of clotting activity than wild-type hFIX in
      the milk (103.76% vs. 49.95%). The highest concentration and clotting activity of
      hFIX reached 26 mug/mL and 1287% in one founder (F(0)-7), which was over 10 times
      higher than that in human plasma. Furthermore, RT-PCR, APTT assay, and
      histological analysis indicated that hFIX was expressed specifically in the
      mammary gland without affecting the intrinsic coagulation pathway and physiologic
      performance of the local tissue.

PMID- 17028785
TI  - Genetic variation and population structure of oriental migratory locust, Locusta
      migratoria manilensis, in China by allozyme, SSRP-PCR, and AFLP markers.
AB  - Allozyme analysis, microsatellite primer PCR (SSRP-PCR), and amplified fragment
      length polymorphism (AFLP) techniques were used to assess genetic diversity and
      population structure of the Chinese oriental migratory locust, Locusta migratoria
      manilensis. A total of 299 PCR markers (67 SSRPs and 232 AFLPs) were detected in
      eight populations, of which 98.7% were polymorphic markers. The proportion of
      polymorphic loci (95.5-98.8%) by SSRP+AFLP markers indicated no significant
      differences between populations, and all populations exhibited a similar level of
      variability; results of the allozyme analysis demonstrated that 19 loci gave rise
      to a lower level of polymorphism (55.6-66.7%). The genetic distances between the
      populations were relatively low. Shannon's index and Nei's gene diversity showed
      low differentiation among the populations. Allozyme analysis, however, reflected
      greater similarity and smaller differentiation between the populations than those
      shown by SSRP and AFLP markers. Neighbor-joining dendrograms derived from both
      the allozyme and SSRP+AFLP markers showed that the genetic distances among
      Chinese oriental migratory locust populations were not greatly influenced by
      geographic distance and breeding habitats.

PMID- 17028786
TI  - Genetic diversity of the giant tiger shrimp (Penaeus monodon) in Thailand
      revealed by PCR-SSCP of polymorphic EST-derived markers.
AB  - A total of 90 ESTs from normal and 157 from subtractive ovarian cDNA libraries of
      the giant tiger shrimp (Penaeus monodon) were sequenced. SSCP analysis of
      disulfide isomerase (DSl), zinc finger protein (ZFP), PMO920, and PMT1700 was
      carried out for population genetic studies of P. monodon in Thai waters. The
      number of codominant alleles per locus for overall samples was 6 for PMO920, 5
      for PMT1700, and 12 for ZFP, and there were 19 dominant alleles for DSI. The
      observed heterozygosity of each geographic sample was 0.3043-0.5128 for PMO920,
      0.3462-0.4643 for PMT1700, and 0.5000-0.8108 for ZFP. Linkage disequilibrium
      analysis indicated that genotypes of these loci segregate randomly (P > 0.05).
      Low genetic distance was found between pairs of geographic samples (0.0077
      0.0178). The neighbor-joining tree constructed from the average genetic distance
      of overall loci allocated the Andaman samples (Satun, Trang, and Phangnga) into
      one cluster, and Chumphon and Trat into other clusters. Geographic
      differentiation between Satun-Trat and Satun-Phangnga was found only at the ZFP
      locus (P < 0.05), suggesting low degrees of genetic subdivision of Thai P.
      monodon.

PMID- 17028787
TI  - Mitochondrial DNA diversity and genetic differentiation of the honeybee (Apis
      cerana) in Thailand.
AB  - Genetic diversity of the honeybee (Apis cerana) in Thailand collected from north,
      northeast, the central region, peninsular Thailand, and Samui Island (n = 181)
      was examined by PCR-RFLP of ATPase6-ATPase8. Interestingly, 78 individuals
      (43.09%) of the southern-latitude bees exhibited length heteroplasmy of the PCR
      product. The gel-eluted ATPase6-ATPase8 (825 bp) of each bee was restricted with
      TaqI, SspI, and VspI, respectively. Eight mitotypes were generated and revealed
      biogeographic differentiation between conspecific samples of A. cerana. AAA, ACA,
      AAD, BAA, ADA, and ABA were found only in the north-to-central samples (north,
      northeast, and central region); BBB and BBC were found in the southern-latitude
      bees; and BBC was restrictively found in the Samui sample. Large genetic
      distances were observed between each of the north-to-central samples and
      peninsular Thailand and Samui samples, but lower levels of genetic distance were
      found within each region. Geographic heterogeneity and phylogenetic analyses
      indicated that Thai A. cerana could be genetically differentiated into northern
      Thailand, peninsular Thailand, and Samui Island populations.

PMID- 17028788
TI  - A new method for the preperative and analytical electrophoresis of cells.
AB  - In this paper, a new method is described for the horizontal electrophoresis of
      cells on a density cushion under near-isopycnic conditions. When cell
      sedimentation is minimized, the electrophoresis of red blood cells (RBC) used as
      model cells within an anti-convective porous matrix (with pores over 300 microm
      in diameter) was capable of separating a mixture of human and chicken RBC
      according to their electrophoretic mobilities. Samples taken from the separated
      RBC bands show over 90% purity for each species. The simultaneous electrophoresis
      of several RBC samples carried out under identical conditions permitted the use
      of comparative data based on the electrophoretic mobility of cells which differ
      in their surface properties. We believe that this relatively simple system, in
      which cell sedimentation and convection are minimized, has the potential to be
      modified and adapted for the separation of other cell types/organelles.

PMID- 17028789
TI  - Helicobacter pylori infection can modulate the susceptibility of gastric mucosa
      cells to MNNG.
AB  - The pathogenesis of stomach cells can be associated with their susceptibility to
      exogenous dietary irritants, like nitrosamines such as dimethylnitrosamines
      (DMNA), and to the effects of non-dietary factors, including Helicobacter pylori
      infection. We used N-methyl-N'-nitro N-nitrosoguanidyne (MNNG) as a surrogate
      agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline
      comet assay, we showed that antioxidants--vitamins C and E, quercetin, and
      melatonin--reduced the genotoxic effect of MNNG in H. pylori-infected and non
      infected human gastric mucosa cells (GMCs). To compare the sensitivity of the
      stomach and the blood, the experiment was also carried out in peripheral blood.
      We observed a higher level of DNA damage induced by MNNG in H. pylori-infected
      than in noninfected GMCs. We did not note any difference in the efficacy of the
      repair of the damage in either type of GMC. H. pylori infection may play an
      important role in the pathogenesis of GMCs, as it can modulate their
      susceptibility to dietary mutagens/carcinogens, thus contributing to gastric
      cancer.

PMID- 17028790
TI  - Swelling of two-dimensional polymer rings by trapped particles.
AB  - The mean area of a two-dimensional Gaussian ring of N monomers is known to
      diverge when the ring is subject to a critical pressure differential, p c ~ N -1.
      In a recent publication (Eur. Phys. J. E 19, 461 (2006)) we have shown that for
      an inextensible freely jointed ring this divergence turns into a second-order
      transition from a crumpled state, where the mean area scales as [A]~N-1, to a
      smooth state with [A]~N(2). In the current work we extend these two models to the
      case where the swelling of the ring is caused by trapped ideal-gas particles. The
      Gaussian model is solved exactly, and the freely jointed one is treated using a
      Flory argument, mean-field theory, and Monte Carlo simulations. For a fixed
      number Q of trapped particles the criticality disappears in both models through
      an unusual mechanism, arising from the absence of an area constraint. In the
      Gaussian case the ring swells to such a mean area, [A]~ NQ, that the pressure
      exerted by the particles is at p c for any Q. In the freely jointed model the
      mean area is such that the particle pressure is always higher than p c, and [A]
      consequently follows a single scaling law, [A]~N(2) f (Q/N), for any Q. By
      contrast, when the particles are in contact with a reservoir of fixed chemical
      potential, the criticality is retained. Thus, the two ensembles are manifestly
      inequivalent in these systems.

PMID- 17028791
TI  - Renormalization group analysis of polymer cyclization with non-equilibrium
      initial conditions.
AB  - We develop a renormalization group approach for cyclizing polymers for the case
      when chain ends are initially close together (ring initial conditions). We
      analyze the behavior at times much shorter than the longest polymer relaxation
      time. In agreement with our previous work (Europhys. Lett. 73, 621 (2006)) we
      find that the leading time dependence of the reaction rate k(t) for ring initial
      conditions and equilibrium initial conditions are related, namely k (ring)(t)
      proportional, variant t (-delta) and k (eq)(t) proportional, variant t (1-delta)
      for times less than the longest polymer relaxation time. Here delta is an
      effective exponent which approaches delta = 5/4 for very long Rouse chains. Our
      present analysis also suggests a "sub-leading" term proportional to (ln t)/t
      which should be particularly significant for smaller values of the renormalized
      reaction rate and early times. For Zimm dynamics, our RG analysis indicates that
      the leading time dependence for the reaction rate is k(t) approximately 1/t for
      very long chains. The leading term is again consistent with the expected relation
      between ring and equilibrium initial conditions. We also find a logarithmic
      correction term which we "exponentiate" to a logarithmic form with a Landau pole.
      The presence of the logarithm is particularly important for smaller chains and,
      in the Zimm case, large values of the reaction rate.

PMID- 17028793
TI  - Is three selected parameters adequate to monitor rheumatoid arthritis?
AB  - This pilot study was done to choose which among the five core set criteria will
      have more discriminating ability and which is easy to administer in a clinical
      setting. Forty-eight patients recently diagnosed to have rheumatoid arthritis
      (RA) were recruited for the study. They were assessed by a rheumatologist in each
      visit (initial and after 2 months of treatment), for five core measures: patient
      assessment, pain (measured on VAS scale), number of tender joints, health
      assessment questionnaire (HAQ) score, and erythrocyte sedimentation rate (ESR).
      All patients were treated with methotrexate 7.5 mg per week and hydroxychloroquin
      400 mg per day with adequate dose of NSAIDs. Patients with associated conditions
      like stroke, ischemic heart disease, and other physical comorbidity were
      excluded. They were categorized as 20, 50, and 70% improvement, if four of the
      five criteria occur. The Wilcoxon signed rank test and discriminant function
      analysis were done to identify the order of importance of measures on influencing
      the outcome. The ESR followed by patient improvement scale showed the least
      changes, while HAQ showed the highest changes. Discriminate function analysis has
      been carried out to see which factors influenced in grouping them for responses
      with post hoc analyses of finding the order of importance of these factors in
      classifying the response. Pain scale, ESR, HAQ score, patient improvement scale,
      and tender score were in the decreasing value of importance. The pain scale, HAQ,
      and ESR, which are more objective and discriminate measures, are useful as
      measures in RA.

PMID- 17028792
TI  - Severity of vertebral fracture reflects deterioration of bone microarchitecture.
AB  - INTRODUCTION: Bone microarchitecture, a component of bone strength, is generally
      measured on transiliac bone biopsy samples. The objective of this study was to
      determine whether assessment of four grades of vertebral fracture severity could
      serve as a noninvasive surrogate marker for trabecular bone volume and
      microarchitecture. METHODS: Baseline vertebral fracture severity was determined
      by semiquantitative assessment of spine radiographs from 190 postmenopausal women
      with osteoporosis. Bone-structure indices were obtained by 2D histomorphometry
      and 3D microcomputed tomography (CT) analyses. Significance of differences was
      determined after adjusting for age, height, and lumbar spine bone mineral
      density. RESULTS: There were significant (P < 0.05) trends in decreasing bone
      volume, trabecular number, and connectivity, and increasing trabecular separation
      with greater vertebral fracture severity. Histomorphometric bone volume was 25
      and 36% lower (P < 0.05) in women with moderate and severe fractures than in
      women with no fractures, respectively. Compared with women without fractures,
      women with mild, moderate, and severe fractures had lower (P < 0.05) microCT bone
      volume (23, 30, and 51%, respectively). CONCLUSIONS: Microarchitectural
      deterioration was progressively worse in women with increasing severity of
      vertebral fractures. We conclude that assessment of vertebral fracture severity
      is an important clinical tool to evaluate the severity of postmenopausal
      osteoporosis.

PMID- 17028794
TI  - Modification of collagen formation using supplemented mesh materials.
AB  - BACKGROUND: Formation of recurrent inguinal and incisional hernia shows an
      underlying defect in the wound healing process. Even following mesh repair an
      altered collagen formation and insufficient mesh integration has been found as
      main reason for recurrences. Therefore the development of bioactive mesh
      materials to achieve a local modification of the scar formation to improve
      patients outcome is advisable. METHODS: Thirty-six male Wistar rats were used
      within this study. A Mersilene (R) mesh sample was implanted after midline skin
      incision and subcutaneous preparation. Before implantation mesh samples were
      incubated for 30 minutes with either one of the following agents: doxycycline,
      TGF-beta 3, zinc-hydrogeneaspartate, ascorbic acid, hyaluronic acid. Incubation
      with a physiologic 0.9 % NaCl solution served as control. Seven and 90 days after
      mesh implantation 3 animals from each group (n = 6) were sacrificed for
      morphological observations. Collagen quantity and quality was analyzed measuring
      the collagen/protein as well as the collagen type I/III ratio. RESULTS: Following
      an implantation interval of 90 days supplementation with doxycycline (39.3 +/-
      7.0 microg/mg) and hyaluronic acid (34.4 +/- 5.8 microg/mg) were found to have a
      significantly increased collagen/protein ratio compared to implantation of the
      pure Mersilene (R) mesh samples (28.3 +/- 1.9 microg/mg). Furthermore, an overall
      increase of the collagen type I/III ratio was found in all groups indicating scar
      maturation over time. However, no significant differences were found after 7 and
      90 days of implantation comparing collagen type I/III ratio of supplemented mesh
      samples and control group. CONCLUSIONS: In summary, we found an influence of
      supplemented mesh materials on collagen deposition. However, the investigated
      bioactive agents with reported influence on wound healing were not associated
      with an improved quality in scar formation.

PMID- 17028795
TI  - Karyotypic analysis of Skimmia japonica (Rutaceae) and related species.
AB  - A karyotypic analysis of three species of Skimmia (Rutaceae) in East Asia was
      performed that examined 88 individuals from 53 localities. Chromosome numbers of
      S. japonica, S. reevesiana and S. arisanensis were 2n=30, 31, 32 (=30+0-2B),
      2n=60 and 2n=60, respectively. The chromosome number of S. arisanensis was
      reported for the first time. All species had a large chromosome pair or quartet
      (the first pair or quartet) with a median-submedian centromere in the karyotype.
      In S. japonica the arm ratio of this first pair was considerably variable and
      showed a geographical pattern. In the northern half of the distribution range,
      Sakhalin, Hokkaido, Honshu, Shikoku and part of Kyushu, the arm ratio was 1-1.2,
      while in the southern half, part of Kyushu, Ryukyu and Taiwan, the arm ratio was
      very variable and ranged from 1.2 to 2.4. In S. japonica the first pair was
      sometimes rather heteromorphic; however, the heteromorphism was not related to
      sex of the plant.

PMID- 17028797
TI  - Osteoclastic bone resorption through receptor tyrosine kinase and extracellular
      signal-regulated kinase signaling in mature osteoclasts.
AB  - It has recently been suggested that signaling through receptor tyrosine kinases
      (RTKs) expressed on mature osteoclasts is involved in osteoclastic bone
      resorption. This study investigated the role and mechanism of two major RTKs
      expressed on mature osteoclasts, fibroblast growth factor receptor type 1 (FGFR1)
      and Tyro 3. Among the FGF receptors (FGFR1-4), only FGFR1 was detected on
      isolated mouse osteoclasts, while all FGFRs were identified on mouse osteoblasts.
      Tyro 3 was seen only in mature osteoclasts among bone cells. FGF-2 moderately
      stimulated pit formation by isolated rabbit osteoclasts at low concentrations
      (>==10(-12) M), whereas at high concentrations (>==10(-9) M) it strongly
      stimulated pit formation by unfractionated bone cells. Gas6, the ligand of Tyro
      3, was expressed ubiquitously in bone cells and stimulated osteoclast function to
      form resorbed pits on a dentine slice. Both FGF-2 and Gas6 upregulated the
      phosphorylation of cellular proteins, including extracellular signal-regulated
      kinase (ERK), and increased the kinase activity of immunoprecipitated FGFR1 and
      Tyro 3, respectively, in mouse osteoclasts. The stimulation of these cytokines on
      mouse and rabbit osteoclast functions was abrogated by PD98059, a specific
      inhibitor of ERK. These results strongly suggest that these cytokines act
      directly on mature osteoclasts through the activation of RTKs and ERK, causing
      the stimulation of bone resorption.

PMID- 17028796
TI  - Functional consequences of stenophylly for leaf productivity: comparison of the
      anatomy and physiology of a rheophyte, Farfugium japonicum var. luchuence, and a
      related non-rheophyte, F. japonicum (Asteraceae).
AB  - We investigated the anatomical and physiological characteristics of stenophyllous
      leaves of a rheophyte, Farfugium japonicum var. luchuence, and sun and shade
      leaves of a non-rheophyte, F. japonicum, comparing three different populations
      from coastal, forest floor, and riparian habitats. Light adaptation resulted in
      smaller leaves, and riparian adaptation resulted in narrower leaves
      (stenophylly). The light-saturated rate of photosynthesis (P (max)) per unit leaf
      area corresponded to the light availability of the habitat. Irrespective of leaf
      size, the P (max) per unit leaf mass was similar for sun and shade leaves.
      However, the P (max) per mass of stenophyllous leaves was significantly lower
      than that of sun and shade leaves. This was because the number and size of
      mesophyll cells were greater than that required for intercellular CO(2)
      diffusion, which resulted in a larger leaf mass per unit leaf area. Higher cell
      density increases contact between mesophyll cells and enhances leaf toughness.
      Stenophyllous leaves of the rheophyte are frequently exposed to a strong water
      flow when the water level rises, suggesting a mechanical constraint caused by
      physical stress.

PMID- 17028798
TI  - Implications of transcriptional coactivator CREB binding protein complexes in
      rheumatoid arthritis.
AB  - Transcriptional coactivators have crucial roles in eukaryotic transcription. It
      has been suggested that one of the coactivators, cAMP response element binding
      protein (CREB) binding protein (CBP), regulates gene expression with a number of
      transcription factors via two mechanisms. One is the recruitment of general
      transcriptional machinery to the promoters. The other is its intrinsic and
      associated histone acetyltransferase (HAT) activity, which increases the
      accessibility of the activator to DNA, and the acetylation of nonhistone
      proteins. Rheumatoid arthritis (RA) is characterized by the inflammation and
      proliferation of synovium, leading to the destruction of articular cartilage and
      bone. To understand the pathogenesis of RA, we focused the transcription
      mechanism through CBP in synoviocytes and chondrocytes. We identified Notch-1 in
      synoviocytes and p34(SEI-1) in chondrocytes as CBP binding proteins by yeast two
      hybrid screening. It was also suggested that the acetylation of p53 could repress
      transactivation in RA synoviocytes. These associations may regulate proliferation
      and apoptosis. This study suggests that regulation of the coactivator could
      become a novel strategy for RA therapy.

PMID- 17028799
TI  - Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis.
AB  - Systemic-onset juvenile idiopathic arthritis (JIA) is a severe and steroid
      dependent disease, which sometimes progresses to the fatal disease macrophage
      activation syndrome. An investigation of inflammatory cytokine levels revealed
      increases in IL-6 in serum of systemic-onset disease patients. Continuously
      elevated levels of IL-6 in serum may play a important role in manifesting the
      clinical symptoms and signs of systemic-onset JIA, including spiking fever, rash,
      arthritis, and serositis. The characteristic fever spikes parallel IL-6 levels.
      Long-term exposure to high levels of IL-6 in children results in severe growth
      impairment, which was strongly suggested by the recent establishment of IL-6
      transgenic mice. To avoid disease progression to macrophage activation syndrome
      and the adverse effects of high-dose corticosteroids, it might be reasonable to
      inhibit the formation of IL-6/IL-6R complex in order to block the binding to
      gp130 receptor, a biologically active receptor for IL-6. This review will provide
      evidence of the relationship between IL-6 homeostasis and systemic-onset JIA, and
      our recent trials of anti-IL-6R antibody (MRA) for children with acute systemic
      disease intractable to long-term and high-dose corticosteroid therapy. MRA could
      be a therapeutic modality for children with systemic-onset JIA intractable to
      high-dose corticosteroids.

PMID- 17028800
TI  - Recombinant adeno-associated virus preferentially transduces human, compared to
      mouse, synovium: implications for arthritis therapy.
AB  - Despite a number of published reports, including from our own laboratory,
      suggesting that adeno-associated virus (AAV) transduces mouse synovium, a careful
      analysis demonstrated transduction predominantly of the subsynovial muscle
      tissue, while the synovial lining is poorly transduced. To investigate the
      potential of AAV to transduce human synovium, three human rheumatoid arthritis
      (RA) and two murine collagen-induced arthritis (CIA) synovial cell lines were
      infected with recombinant AAV (rAAV) vectors encoding either mouse IL-10 or IL-4.
      Low-level transgene expression was observed. However, either Gamma-irradiation or
      the addition of a low-titer E1-, E3-deleted recombinant adenovirus resulted in up
      to a 100-fold increase in transgene product in the human, but not the mouse, cell
      lines. RA synovial tissues implanted subcutaneously in severe combined
      immunodeficiency (SCID) mice, which were subsequently infected with rAAV, showed
      marked increases in transgene expression when co-infected with adenovirus. To our
      knowledge, this is the first study to show that intact human synovial tissues can
      be transduced by rAAV, and it suggests that murine arthritis may not be an
      optimal model to study rAAV as a gene transfer vector. Further studies to
      elucidate the mechanisms limiting gene transduction in human synovium may allow
      optimization of this vector for the treatment of arthritis.

PMID- 17028801
TI  - Effect of ebselen, a scavenger of reactive oxygen species, on chondrocyte
      metabolism.
AB  - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a synthetic heterocyclic
      seleno-organic compound, has been shown to act as a scavenger of reactive oxygen
      species (ROS). We have previously reported that interleukin-1 (IL-1) inhibited
      proteoglycan (PG) synthesis and induced the production of ROS in cartilage
      explants and isolated chondrocyte cultures. In this study, we report the
      protective effect of ebselen against IL-1-mediated inhibition of PG synthesis and
      ROS induction in cultured cartilage explants and chondrocytes. Ebselen also
      reversed the inhibition of PG synthesis in mechanically stressed cultured
      chondrocytes. These data suggest that the use of the antioxidant ebselen may be a
      useful tool for studying the mechanisms of cartilage degradation.

PMID- 17028802
TI  - Radiological follow-up study of rheumatoid wrists after radio-lunate limited
      arthrodesis with ulnar head resection.
AB  - Radio-lunate limited arthrodesis (RLA) is an established surgical intervention
      for damaged rheumatoid arthritis (RA) wrists. The goal of RLA is to conserve the
      range of motion (ROM) and level of activities of daily life (ADL) by delaying
      more extensive fusion. In this study, we retrospectively reviewed the outcome of
      RLA with ulnar head resection (UHR) in terms of pain score, ROM, and radiographic
      parameters, including carpal height ratio, ulnar translation ratio, and palmar
      subluxation. The clinical factors, such as dose of corticosteroids per day and
      laboratory examination data before surgery, including C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), did not
      influence the results of the surgery. The changes in these clinical factors were
      also statistically analyzed in relation to the Schulthess classification of
      preoperative radiographs of wrists reported by Simmen and Huber: Type I
      (ankylosis type), Type II (osteoarthritis type), and Type III (disintegration
      type). This study hypothesized that RLA with UHR would provide no significant
      improvement in Type III wrists. The results showed that RLA with UHR resulted in
      stable wrists with excellent pain relief and with limited, but temporary,
      functional ROM, suggesting that this procedure seems to be applicable for all
      types of wrists within this group of patients.

PMID- 17028803
TI  - HLA-DRB1 haplotype did not affect the medium-term results of total knee
      arthroplasty in patients with rheumatoid arthritis.
AB  - This study investigated whether the HLA-DRB1 "susceptible allele" (SA) genotype
      is predictive for total knee arthroplasty (TKA) failure in patients with
      rheumatoid arthritis (RA). The results of 49 TKAs (30 RA patients) with an
      average follow-up of 7.9 years (range 5-15 years) were analyzed using a 12-item
      questionnaire and the Knee Society system. HLA-DRB1 alleles were used to estimate
      the severity of RA and divide the patients into three categories depending upon
      the gene dose of SA (SA+/+, SA+/-, and SA-/-). For all three categories, the 12
      item questionnaire had significantly improved postoperatively, but without
      significant difference. We divided the 12 items of the questionnaire into two
      groups: knee-relevant parameters and general parameters. Patients in all three
      groups improved similarly in knee-relevant parameters. In contrast, those
      homozygous for SA (SA+/+) benefited less in general parameters. The average
      radiolucency score was 1.87 mm, with no difference being detected among the three
      groups. The HLA-DRB1 genotype did not affect the survival of the knee implants.
      Overall, patients without the RA-associated HLA gene benefited most from TKA as
      they improved not only in knee function, but also in parameters of general
      functional status.

PMID- 17028804
TI  - Efficacy of plasma exchange therapy for Kawasaki disease intractable to
      intravenous gamma-globulin.
AB  - Kawasaki disease (KD) causes coronary artery lesions (CALs) in 500 Japanese
      children each year. Intravenous gamma-globulin (IVGG) decreases the incidence of
      these lesions from 25% to 8% of the total KD cases. We examined whether plasma
      exchange is a safe and effective prophylaxis against CALs in children with KD
      intractable to IVGG therapy. Eighty-nine children with KD at high risk of CALs
      were selected on the basis of increases in fractional changes in inflammatory
      markers such as white blood cell count, neutrophil count, and C-reactive protein
      between the baseline and 1-2 days after IVGG treatment. Of 105 children who
      received a second course of IVGG therapy because the initial course was
      ineffective, plasma exchange (PE) was performed in 46 children who had not
      responded to the second IVGG treatment. The outcome was compared with the results
      when a third course of IVGG therapy was given to the other 59 children. No
      complications occurred with the plasma exchange therapy. CALs developed in only 8
      of the 46 children (17.3%) who underwent plasma exchange, but they occurred in 24
      of the 59 (40.7%) who had received a third course of IVGG therapy (P << 0.0012).
      We concluded that PE was a safe, effective prophylactic measure against CALs in
      children with KD intractable to IVGG therapy. PE should be performed at an early
      stage, as soon as fractional increases in inflammatory markers are found after
      IVGG therapy.

PMID- 17028805
TI  - Total ankle arthroplasty for deformity of the foot in patients with rheumatoid
      arthritis using the TNK ankle system: clinical results of 21 cases.
AB  - We report the results of total ankle arthroplasty (TAA) of 21 ankle joints
      performed on 19 patients with rheumatoid arthritis (RA) using the Japanese TNK
      ankle system. The clinical evaluation for an average follow-up period of 33.8
      months was based on the ankle analysis system. The total score, pain score, range
      of motion, and walking ability significantly improved postoperatively compared
      with the preoperative period. These parameters also showed significantly
      different values between the preoperative and the follow-up periods. However, the
      range of motion significantly improved postoperatively. In the evaluation of TAA
      using the TNK ankle system, a radiolucent line of about 1 mm was detected, but
      there was no dislocation or sinking of the tibial and talar prostheses. There
      were no severe complications except for two cases with a delayed wound healing
      and one with a deep infection. These results suggest that if the talocrural joint
      only was destroyed and the neighboring joints (subtalar or talonavicular) had
      fibrous fusion, or the patient had relatively fewer activities in daily life or
      was an elderly person, TAA using the TNK ankle system was effective for the
      treatment of painful and disabling ankle joints in patients with RA in the middle
      of the follow-up period.

PMID- 17028806
TI  - Requirement of mitogen-activated protein kinase for collagenase production by the
      fibronectin fragment in human articular chondrocytes in culture.
AB  - Fibronectin fragments have been shown to up-regulate matrix metalloproteinase
      production in chondrocytes. We investigated the roles of mitogen-activated
      protein kinase (MAPK) pathways activated by the COOH-terminal heparin-binding
      fibronectin fragment (HBFN-f) in collagenase production by human chondrocytes in
      culture. In articular cartilage explant culture, HBFN-f stimulated type II
      collagen cleavage by collagenase in association with increased secretion of MMP-1
      and MMP-13. In human articular chondrocytes, HBFN-f induced the collagenases with
      activation of the extracellular signal-regulated kinase (ERK), p38, and the c-Jun
      NH(2)-terminal kinase (JNK). PD98059 that inhibits the ERK pathway blocked HBFN-f
      stimulated production of MMP-1 and MMP-13 in explant culture. SB203580 at 1
      microM, the concentration that inhibits p38 only, partially suppressed HBFN-f
      induced collagenase production, whereas at 10 microM, the inhibitor that blocks
      both p38 and JNK almost completely inhibited collagenase induction. PD98059 and
      SB203580 individually blocked HBFN-f-increased cleavage of type II collagen in
      the explant culture, although 10 microM SB203580 strongly inhibited the collagen
      cleavage compared with 1 microM of the inhibitor. These results indicate that
      collagenase production leading to type II collagen cleavage in cartilage explants
      requires ERK, p38, and JNK.

PMID- 17028807
TI  - A case of lupus cystitis with a history of idiopathic thrombocytopenic purpura.
AB  - A 36-year-old Japanese woman who had been diagnosed as having systemic lupus
      erythematosus (SLE) at the age of 34 began to complain of severe bowel symptoms
      and developed severe hydroureteronephrosis. She had a history of idiopathic
      thrombocytopenic purpura. Biopsy specimens from her bladder showed interstitial
      cystitis. She was diagnosed as having lupus cystitis, and treated with
      intravenous methylprednisolone pulse therapy followed by oral prednisolone and
      ureter catheterization. Her urinary and bowel symptoms were alleviated and the
      level of hydroureteronephrosis improved. We note that cystitis could be a primary
      manifestation of SLE. Patients not only with SLE but also with some autoimmune
      diseases require careful urological evaluation when they complain of severe bowel
      symptoms.

PMID- 17028808
TI  - Munchausen syndrome with foreign-body granuloma mimicking rheumatic diseases.
AB  - A 37-year-old man was admitted to our hospital because of fever, polyarthralgia,
      and subcutaneous tumors. There was swelling of the bilateral wrists and ankles,
      and subcutaneous tumors over the bilateral elbow joints. Despite his complaints
      of multiple symptoms, clinical investigations failed to reveal any abnormality.
      Although laboratory parameters improved rapidly after steroid therapy, the
      symptoms remained unchanged, and there was an enormous discrepancy between the
      laboratory data and his symptoms. A biopsy specimen from one of the subcutaneous
      tumors revealed foreign-body granuloma associated with a foreign body fragment.
      Because the nursing staff later discovered that the patient had been carrying out
      self-injection, a diagnosis of Munchausen syndrome was made. Munchausen syndrome
      should be included in the differential diagnosis of rheumatic diseases.

PMID- 17028810
TI  - A case of Weber-Christian disease associated with myelodysplastic syndrome.
AB  - We report the case of a 73-year-old man with myelodysplastic syndrome (MDS) who
      developed Weber-Christian disease (WCD). Bone marrow aspirates showed refractory
      anemia with abnormal karyotypes such as trisomy 8, trisomy 8 and 14, and trisomy
      8, 9, and 14. The patient had intermittent fever associated with multiple tender
      erythematous nodules on the skin. A biopsy sample taken from a nodule revealed
      focal subcutaneous infiltration of neutrophils and necrotizing fat tissue. We
      diagnosed the patient as having lobular panniculitis associated with
      myelodysplastic syndrome. The serum levels of soluble interleukin-2 (IL-2)
      receptor, interferon-Gamma, IL-1-Beta, IL-6 and tumor necrosis factor-Alpha were
      elevated in the active state but returned to normal after prednisolone therapy.
      This finding appears to implicate a T-cell immune response in the pathogenesis of
      Weber-Christian disease.

PMID- 17028809
TI  - Abacterial prostatitis and primary biliary cirrhosis with SjOgren's syndrome.
AB  - In patients with SjOgren's syndrome (SS), the salivary and lacrimal glands are
      often affected, although other epithelial tissues can become inflamed. Here, we
      report the first case of abacterial prostatitis in a patient with SS complicated
      by primary biliary cirrhosis. Histologically, the distribution and subpopulation
      of infiltrating lymphocytes were similar in the salivary gland, liver, and
      prostate. Treatment with steroid was successful. We speculate that the prostate
      may be one of the target organs in SS.

PMID- 17028811
TI  - Hemagglutination of preoperative blood donation in patients with rheumatoid
      arthritis.
AB  - We gave preoperative blood transfusions to 37 patients with rheumatoid arthritis
      (RA) and 35 patients with osteoarthritis (OA), including some whose baseline
      hemoglobin level was less than 10 g/dl. Transfusion packs can preserve whole
      blood containing citrate phosphate dextrose (CPD) for 3 weeks. The baseline
      hemoglobin level of RA cases was 10.4 g/dl (range 8.4-13.1 g/dl), and that of OA
      cases was 11.9 g/dl (range 10.4-15.0 g/dl). By collecting 200-400 g every week
      before the operation, the total was 800-1200 g. Erythropoietin was given to
      patients intramuscularly when their hemoglobin was less than 13 g/dl after blood
      had been collected. Hemagglutination, with diameters of more than 1 cm, made
      filter occlusions in 11 RA cases (30%) and one OA case (3%) (P << 0.0031) after
      retransfusion. There were no differences between hemagglutination patients
      (agglutination group) and nonhemagglutination patients (nonagglutination group)
      regarding baseline C-reactive protein (CRP), white blood cells, platelets, or
      fibrinogen. We could not predict the formation of macrohemagglutination in the
      packs collected during the clinical course. In RA cases, allogenic transfusions
      were performed for four cases (36%) in the agglutination group and for one case
      (12%) in the nonagglutination group. Preoperative transfusion for the RA patients
      showed hemagglutination in some cases, and highlighted the need for modifications
      to reduce these hemagglutinations.

PMID- 17028812
TI  - Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin
      treatment for superficial bladder carcinoma: report of six cases.
AB  - We report the cases of six patients who developed acute Reiter's syndrome
      following intravesical bacille biliE de Calmette-GuErin (BCG) immunotherapy for
      superficial bladder cancer. After the third to eighth BCG intravesical injection,
      the patients developed conjunctivitis, aseptic urethritis, and polyarthritis
      consistent with a diagnosis of Reiter's syndrome. HLA-B27 antigen was negative in
      five of the patients examined. Two of the patients responded to nonsteroidal anti
      inflammatory drugs for polyarthritis, and the other four responded to steroids
      (prednisolone 5-10 mg/day). The frequent use of intracavitary BCG may increase
      the incidence of BCG-induced Reiter's syndrome. Further analysis of the
      relationship between HLA-B and -DR alleles and arthritis should shed light on the
      mechanism of BCG-induced Reiter's syndrome.

PMID- 17028813
TI  - Gait analysis in an osteoarthritis patient with restoration of the hip joint
      space following contralateral total hip arthroplasty: a case report.
AB  - We present the case of a patient who, after undergoing unilateral total hip
      arthroplasty (THA), achieved pain reduction in the contralateral hip accompanied
      by restoration of the radiographic joint space. We conducted gait analysis to
      clarify the dynamic factors affecting the natural course of osteoarthritis (OA).
      Our findings revealed that the patient walked with exaggerated adduction of the
      hip following the contralateral THA, causing substantial regeneration of joint
      loading.

PMID- 17028814
TI  - Revised list of acronyms.

PMID- 17028815
TI  - Proposed [corrected] Japanese guidelines for the use of infliximab for rheumatoid
      arthritis.
AB  - Differences in ethnic backgrounds as well as in medical and socioeconomic status
      often affect both the efficacy and adverse effects of medications. Recent data
      suggest an increased risk of opportunistic infections, especially tuberculosis
      (TB), among rheumatoid arthritis (RA) patients receiving infliximab, a chimeric
      monoclonal anti-tumor necrosis factor alpha (TNF-alpha) antibody. In this regard,
      the annual incidence of TB is approximately five times higher in Japan than in
      the United States. Furthermore, since Bacillus Calmette-Guerin vaccination is
      mandatory in childhood when the skin test for purified protein derivative (PPD)
      is negative, a high incidence of false-positive PPD skin tests is observed among
      the Japanese population. In addition, the upper limit of methotrexate dosage to
      be used for RA is lower in Japan. We have therefore established official
      guidelines for the proper use of infliximab in Japanese RA patients. In this
      review, an algorithm for the diagnosis and management of TB in RA is presented in
      an evidenced-based form.

PMID- 17028816
TI  - The low-throughput protein A adsorber: an immune modulatory device. Hypothesis
      for the mechanism of action in the treatment of rheumatoid arthritis.
AB  - To achieve specific removal of pathogenic antibodies (Ab) or immune complexes
      (IC), several adsorbers have been developed. We discuss the mode of action of low
      throughput staphylococcal protein A (SPA) immunoadsorption. The SPA-based
      Prosorba apheresis is likely to modify some of the autoantibodies (autoAb) or IC.
      The low-throughput adsorber showed very limited adsorption capacity of
      circulating autoAb and/or circulating IC. Besides changes of humoral diagnostic
      parameters, cellular changes could be observed in the Prosorba-treated patients.
      These changes were rather similar to those that have been observed in a patient
      successfully treated with Ab against tumor necrosis factor alpha. We propose an
      adsorber-catalyzed conversion of small, tissue-penetrating, scarcely detectable,
      non-complement-binding, proinflammatory IgG-rheumatoid factor (RF)-based IC into
      the more readily phagocytosed species of IC: intermediate-sized, partially
      cryoprecipitable, non-tissue penetrating IC that are opsonized with complement.
      These IC are rather short-lived and could quickly be cleared by the body's
      scavenging system.

PMID- 17028817
TI  - Intracellular signal transduction pathways: good therapeutic targets for joint
      destruction in rheumatoid arthritis.
AB  - Preventing joint destruction is one of the most challenging issues in treating
      patients with rheumatoid arthritis (RA), and I propose that intracellular
      signaling pathways in osteoclasts and synovial fibroblastic cells (SFCs) can be
      good therapeutic targets. Osteoclasts are primarily involved in the bone
      destruction in RA joints, and SFCs support osteoclast differentiation and
      activation by producing various proinflammatory cytokines including receptor
      activator of NF-kappaB ligand (RANKL), the osteoclast differentiation factor
      belonging to the tumor necrosis factor-alpha superfamily. Suppressing c-Src
      pathways by adenovirus vector-mediated C-terminal Src family kinase (Csk) gene or
      Ras/extracellular-regulating kinase (ERK) pathways by introducing dominant
      negative Ras (Ras(DN)) adenovirus reduced osteoclastic bone resorption as well as
      the abnormal proliferation and interleukin-6 production of SFCs, and the local
      injection of these viruses ameliorated the joint destruction in adjuvant
      arthritis rats. Moreover, chondrogenic differentiation of SFCs could be induced
      by stimulating activin receptor-like kinase 3 pathways.

PMID- 17028818
TI  - Overcoming treatment unresponsiveness mediated by P-glycoprotein overexpression
      on lymphocytes in refractory active systemic lupus erythematosus.
AB  - P-glycoprotein (P-gp) expels various drugs from cells, resulting in multidrug
      resistance, including against glucocorticoids. Here, we present a case of
      systemic lupus erythematosus (SLE) that suggests the importance of initial
      intensive treatment in overcoming unresponsiveness due to P-gp overexpression on
      activated lymphocytes. A 28-year-old woman had been diagnosed with highly active
      SLE including severe pericarditis, hemolytic anemia, lupus nephritis, and
      retinopathy. The disease activity of SLE progressed despite 1 mg/kg per day oral
      prednisolone. At the time, P-gp expression was extremely high, as evaluated by
      flow cytometric analysis on peripheral lymphocytes. After intensive treatment
      with three courses of methylprednisolone pulse therapy and plasmapheresis, we
      succeeded in controlling disease activity in association with marked reduction of
      P-gp overexpression; namely, the clinical symptoms immediately improved along
      with the reduction of P-gp expression. These results imply that patients with
      highly active SLE might have drug unresponsiveness that is mediated by P-gp
      overexpression on lymphocytes. Therefore, downregulation of P-gp by initial
      intensive immunosuppressive therapy might be important for overcoming
      glucocorticoid resistance. We also propose that measurement of P-gp on
      lymphocytes is a useful test for prediction of drug resistance and may assist in
      the selection of appropriate initial treatment.

PMID- 17028819
TI  - Doppler sonographic analysis of synovial vascularization in knee joints of
      patients with rheumatoid arthritis: increased color flow signals and reduced
      vascular resistance.
AB  - Synovial vascularization was analyzed by power Doppler and spectral Doppler
      sonography in 42 knee joints of 28 patients with rheumatoid arthritis. The
      synovial vessels with greater intensity of color flow signals demonstrated
      significantly lower indicators of vascular resistance - resistive index (P <
      0.01) and pulsatility index (P < 0.01) - than those with lesser intensity.
      Consequently, an inverse correlation was observed between intensity of color flow
      signals and both resistive index (P < 0.01) and pulsatility index (P < 0.01).

PMID- 17028820
TI  - Doppler sonographic evaluation of effect of treatment with infliximab (Remicade)
      for rheumatoid arthritis.
AB  - Synovial vascularization in the knee joints of six patients with rheumatoid
      arthritis who were treated with infliximab was evaluated by Doppler sonography.
      Power Doppler sonography demonstrated a significant reduction of color flow
      signals (P < 0.05), and spectral Doppler sonography demonstrated a significant
      increase in vascular resistance (P < 0.05) at week 6 (after three injections)
      evaluation of the therapy. A significant decrease in the number of tender joints
      (P < 0.05) and C-reactive protein value (P < 0.05) was also observed in these
      patients.

PMID- 17028821
TI  - Musculoskeletal pain in Japan: prevalence and interference with daily activities.
AB  - We estimated the prevalence of musculoskeletal pain in five anatomical areas and
      their interference with daily activities (IDA) in a Japanese adult population (n
      = 3188). A questionnaire survey was conducted among participants in health
      examinations at three health care centers. On a drawing with predefined body
      regions, participants marked the regions affected by pain and the regions
      affected by IDA due to the pain, respectively. Overall prevalence of
      musculoskeletal pain was 41.4% (M 40.9%, F 42.2%) with a significant increase
      with age. Neck and shoulder area showed the highest prevalence of pain (20.3%; M
      19.6%; F 21.3%), followed by lower back area (19.1%; M 20.1%; F 17.5%), hip and
      knee area (11.1%; M 9.1%; F 14.3%), elbow, wrist, and hand area (7.4%; M 6.6%; F
      8.6%), and ankle and foot area (5.8%; M 5.5%; F 6.3%). Overall percentage of IDA
      in musculoskeletal pain was 20.5%. After adjustment for age and sex, the ranking
      of percentage of IDA in the pain was: (1) neck and shoulder area (31.0%), (2)
      elbow, wrist, and hand area (21.5%), (3) ankle and foot area (18.8%), (4) lower
      back area (17.9%), and (5) hip and knee area (17.4%). Overall percentage of
      treatment for musculoskeletal disorders was 6.6% (M 4.7%, F 9.7%), which remained
      28.1% (M 21.6%, F 38.0%) even in those who described IDA due to pain. According
      to our estimates, 42.2 million (41.2%) of Japanese adults might suffer from
      musculoskeletal pain and 9.1 million (8.8%) might encounter IDA due to the pain.
      Because of high prevalence and IDA, musculoskeletal pain is one of the health
      problems to be given high priority in Japan.

PMID- 17028822
TI  - Burden of musculoskeletal pain in Japan.
AB  - Based on the prevalence of musculoskeletal pain in the context of interference
      with daily activities (IDA) and treatment for musculoskeletal disorders in the
      study population (n = 3188), we estimated the prevalence and years lived with
      disability (YLD) of musculoskeletal pain in Japan. The total of 42,287 thousand
      (41.2%) of Japanese adult people was estimated to suffer from musculoskeletal
      pain. Among them, 9127 thousand was estimated to interfere with daily activities
      due to the pain. Overall YLD for musculoskeletal pain in Japan were estimated at
      1,297,843.7 (1263.6 per 100,000). The YLD for Pain without IDA were 33,159.3
      (32.3 per 100,000) and the YLD for Pain with IDA were 1,264,684.4 (1231.3 per
      100,000). One-way sensitivity analysis showed that the YLD of musculoskeletal
      pain might increase to 4,421,844.0 (4305.2 per 100,000) with the increased
      disability weight for Pain without IDA of 0.1, while they might inversely
      decrease to 1,018,875.0 (992.0 per 100,000) with the increased treatment rate in
      Pain with IDA of 100%. Musculoskeletal pain imposes a substantial burden on the
      Japanese adult population. To allow the population to keep their health-related
      quality of life, health professionals should pay more attention to
      musculoskeletal pain and make positive efforts to improve prevention and control
      of musculoskeletal pain.

PMID- 17028823
TI  - Observation of retrieved ceramic-on-ceramic articular surface: a case of revised
      total hip arthroplasty due to failure of the support ring.
AB  - We report the case of a 63-year-old woman who required revision surgery for
      ceramic-on-ceramic total hip arthroplasty (THA) due to failure of the support
      ring. We retrieved the ceramic cup and head, observed it macroscopically and
      measured it to determine its shape condition (sphere diameter, sphericity, and
      circularity) and surface condition (surface roughness by scanning electronic
      microscopy). Although abrasion was not found at the sliding surface of either the
      cup or head, it was observed at the edges of the cup and at one part of the head.
      We point out the risk of the edge contact and conclude the possibility of micro
      motion between the cup and the head during walking or loading in vivo, and that
      contact had taken place at such parts.

PMID- 17028824
TI  - HLA-B52-positive vasculo-Behcet disease: usefulness of magnetic resonance
      angiography, ultrasound study, and computed tomographic angiography for the early
      evaluation of multiarterial lesions.
AB  - We report a case of HLA-B52-positive Behcet disease accompanied by multiarterial
      lesions. A 24-year-old woman was suffering from sporadic high fever and recurrent
      oral and genital ulcers, and laboratory data revealed severe inflammation. A
      diagnosis of Behcet disease was made. Magnetic resonance angiography, ultrasound
      study, and computed tomographic angiography demonstrated multiarterial lesions
      that had caused no symptoms. These noninvasive examinations were extremely useful
      in evaluating asymptomatic early vascular lesions.

PMID- 17028825
TI  - Rapidly aggravated Mycobacterium avium infection in a patient with rheumatoid
      arthritis treated with infliximab.
AB  - Infliximab was introduced along with methotrexate 8 mg/week to a female patient
      with intractable rheumatoid arthritis. Although a dramatic improvement of her
      arthritic symptoms was achieved immediately, a small nodular shadow developed in
      the right middle field of her lung, visible on chest X-ray at the third
      injection. Because the nodular shadow rapidly increased its size in a week,
      transbronchial fiberoptic examination was performed and lavage fluid was
      obtained. The polymerase chain reaction was positive for Mycobacterium avium and
      the bacterial growth in culture confirmed the diagnosis. Although tuberculosis is
      a well-known adverse reaction to infliximab, development of nontuberculous
      mycobacteriosis is quite rare and no such report has so far been published in the
      context of infliximab usage. We should be alert to the fact that nontuberculous
      mycobacteriosis of slow progression in a usual clinical setting progresses quite
      rapidly, thus treatment should not be delayed, especially in patients on
      infliximab.

PMID- 17028826
TI  - Water intoxication associated with moderate dose of cyclophosphamide pulse
      therapy in an elderly patient: a case report and literature review.
AB  - Intravenous high-dose cyclophosphamide infusion, usually performed to treat
      malignant neoplasms, is known to cause water intoxication. Intravenous
      cyclophosphamide pulse therapy (IVCY) is increasingly being employed for the
      treatment of rheumatic diseases as well. Recently, water intoxication has been
      reported to occur even after low-to-moderate doses of IVCY. In the present paper,
      we describe a case of polyarteritis nodosa in a patient in whom water
      intoxication developed after IVCY at a moderate dose. Hydration is usually
      performed to maintain sufficient urine flow to avoid cystitis. Based on our case
      and a review of the literature, it is recommended that hydration should be
      carefully performed during IVCY in order to avoid water intoxication, especially
      when treating elderly patients.

PMID- 17028827
TI  - Systemic lupus erythematosus in identical twins: a case report.
AB  - In this report we describe the case of identical twin sisters that developed
      systemic lupus erythematosus (SLE). These patients have in common major
      histocompatibility complex class I and class II alleles and identical red blood
      cell antigens, which is a clear indication of monozygotic twins. Both twins
      showed high titers of anti-dsDNA antibody. However, only one of them manifested
      signs of lupus psychosis and was positive for the LE test, rheumatoid factor,
      anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived
      together; therefore, the environmental factors were considered to be the same.
      Interestingly, these patients expressed different types of autoantibodies and the
      manifestation of disease was also quite different. When one of the twins was
      diagnosed with SLE, we began to closely follow up signs of the disease in the
      other twin periodically. This enabled us to promptly diagnose the second twin
      with SLE and she was successfully treated without progression of the disease. It
      is important to mention that following up the subsequent history of an identical
      twin diagnosed with SLE allowed early detection of the disease in the other twin.

PMID- 17028828
TI  - A case of interstitial cystitis accompanying Sjogren's syndrome.
AB  - A 51-year-old woman with interstitial cystitis was referred for screening of
      autoimmune disease. She was positive for results of Schirmer and Saxon tests and
      for ss/A and ss/B antibodies. Autoantibodies to type 3 muscarinic acetylcholine
      receptor were detected in the patient's serum by Western blotting. We diagnosed
      her as having interstitial cystitis accompanying Sjogren's syndrome. To enable
      early treatment, interstitial cystitis should be considered when patients with
      Sjogren's syndrome complain of urinary symptoms.

PMID- 17028829
TI  - [Genetic research: chance or risk for health?].

PMID- 17028831
TI  - [Federal Environmental Department Commission "Human Biomonitoring": Report of the
      Commission].

PMID- 17028832
TI  - [Microbiological detection procedures according to Water Supply V 2001. List of
      alternative procedures according to 15 Abs. 1 Water Supply V 2001 --1.
      Notification of change: Notification of the Federal Environmental Department ].

PMID- 17028836
TI  - Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal
      rule.

PMID- 17028834
TI  - Ischemic proctitis following Delorme procedure for external rectal prolapse.

PMID- 17028837
TI  - Cell membrane-derived lysophosphatidylcholine activates cardiac ryanodine
      receptor channels.
AB  - Lysophosphatidylcholine (LPC) is metabolized from a membrane phospholipid and
      modulates a variety of channels in the plasma membrane (PM). We examined LPC
      modulation of cardiac ryanodine receptor (RyR) channels in the sarcoplasmic
      reticulum (SR) using the planar lipid bilayer method to measure the single
      channel currents. Micromolar concentrations of LPC increased the open probability
      of the reconstituted RyR channels irrespective of whether LPC was added to the
      cis or trans chamber. LPC also increased the membrane capacitance of the bilayer.
      The effects of LPC contrasted well with those of sphingosylphosphorylcholine
      (SPC). Taken together, these results suggest that amphipathic lipid LPC does not
      bind directly to the RyR channel protein, but rather, is incorporated into the
      bilayer membrane and activates the channel. Thus, we consider cell membrane
      derived LPC to be a putative endogenous mediator that activates not only plasma
      membrane channels but also RyR channels and induces arrhythmogenic Ca(2+)
      mobilization in cardiomyocytes.

PMID- 17028838
TI  - Whole-body MR vascular screening detects unsuspected concomitant vascular disease
      in coronary heart disease patients.
AB  - Coronary heart disease (CHD) patients often show atherosclerotic vascular disease
      in other vascular territories. We evaluated how often whole-body MR imaging
      detects concomitant arterial pathologies in CHD patients, and how often these
      pathologies were not known to the patients previously. Of 4,814 participants in
      the population-based Heinz Nixdorf Recall Study, 327 reported CHD (i.e., previous
      coronary bypass surgery, angioplasty); of those, 160 patients (mean age 66.4
      years) were examined using MR of the brain, the heart (excluding the coronary
      arteries), and whole-body MR angiography. The prevalence of each vascular
      pathology was assessed, correlated to the others and compared to patients'
      histories. Of the 160 CHD patients, 16 (10%) showed MR signs of stroke, and 77
      (48.1%) had a stenosis >50% in at least one extracerebral peripheral artery
      (other than the coronaries), including 28 (17.5%) with relevant renal artery
      stenoses, and 20 (12.5%) with relevant extracerebral internal carotid artery
      stenoses. False negative histories were reported in 12 of 81 cases with
      myocardial infarctions, and in 11 of 16 cases with cerebrovascular infarctions.
      This whole-body atherosclerosis MR screening program allows previously unknown
      concomitant vascular disease to be detected in coronary heart disease patients.
      Its prospective value should be assessed in further studies.

PMID- 17028839
TI  - [Recurring nose bleeds, dyspnea and conspicuous findings in the lung and liver].

PMID- 17028840
TI  - [Sturge-Weber syndrome. Early manifestation and visualization of disease course].
AB  - BACKGROUND: The purpose of this study was to evaluate ultrasound, MRI, and CT
      investigations in children with Sturge-Weber syndrome. PATIENTS AND METHODS: From
      1996 to 2005, a total of 15 investigations of the brain performed in 6 children
      with Sturge-Weber syndrome were reviewed. We evaluated four ultrasound, five CT,
      and six MRI exams. RESULTS: With ultrasound an increase of the echogenicity of
      the periventricular white matter was depicted in the first days of life. MRI is
      the best modality to demonstrate the vascular malformation, the impaired cerebral
      venous drainage, and the atrophy of one hemisphere. CONCLUSIONS: One-sided
      periventricular hyperechogenicity on ultrasound can be an early sign of Sturge
      Weber syndrome in children with a nevus flammeus. MRI is the method of choice to
      diagnose Sturge-Weber syndrome and to follow up these children if the
      neurological status of the patients changes.

PMID- 17028841
TI  - [Acute lid swelling].

PMID- 17028842
TI  - [Relevant secondary findings in magnetic resonance imaging of the heart using the
      examples of a bronchial carcinoma and a malignant lymphoma].
AB  - BACKGROUND: Here we consider the prevalence of extracardiac findings in the
      standard sequences and planning surveys of cardiac MRI. PATIENTS AND METHODS:
      Over a period of 2 years, 363 patients (261 men, 102 women) with different
      clinical diagnoses were examined by cardiac MRI. The MRI protocol included a
      planning survey in three planes and standard sequences in long and short axis
      orientation. RESULTS: A total of 53 extracardiac findings were detected: 1
      lymphoma, 1 bronchogenic carcinoma, 1 retroperitoneal hematoma, 1 mediastinal
      lymphadenopathy, 1 tumor of the adrenal glad, 16 pleural effusions, 14 renal
      cysts, 12 liver cysts, 2 pulmonary infiltrate, 1 atelectasis, 2
      cholecystolithiasis, 1 diaphragmatic elevation, 1 hiatus hernia. CONCLUSION:
      Evaluation of the standard sequences and the planning surveys is useful for
      discovering extracardiac findings in a cardiac MRI and should be carried out
      routinely.

PMID- 17028844
TI  - [Merkel cell carcinoma of the upper lid].
AB  - AIMS: Merkel cell carcinoma (MCC) of the skin is a rare form of cutaneous
      malignancy of neuroendocrine origin with a propensity to form cutaneous and
      lymphogenous metastases. The tumor, affecting predominately elderly patients, has
      a significantly higher incidence in female patients (80%) compared to male
      patients (20%). The mainstay of therapy is surgical resection with possible
      adjuvant radio- or chemotherapy. CASE REPORT: A case of a 78-year-old patient
      with a MCC of the upper lid without lymph node involvement or distant metastasis
      is described. The tumor was resected and the defect closed by a temporal skin
      flap performing a temporary cantholysis. The clinical follow-up revealed an
      undisturbed eye lid function without any clinical or radiological signs of a
      locoregional or distant recurrence.

PMID- 17028843
TI  - [Hyperplasia of the coronoid process: diagnosis and treatment].
AB  - STUDY GOAL: As it is an unusual and infrequent clinical entity, hyperplasia of
      the coronoid process is often overlooked or diagnosed too late. The aim of this
      study was to characterize the morphology, etiology, and clinical picture of
      coronoid hyperplasia as well as to discuss its diagnosis and treatment. MATERIALS
      AND METHODS: All cases of histologically confirmed hyperplasia of the coronoid
      process treated in our center between 1995 and 2004 were analyzed. Patient data
      were evaluated with respect to age, gender, clinical symptoms, diagnostic work
      up, and treatment. The extracted data were compared to those found in the
      literature. RESULTS: The study included 14 new cases and 101 cases already
      published: 96 with bilateral and 19 with unilateral hyperplasia. At the time of
      diagnosis, the subjects' mean age was 23.7 years. The patients in Bonn were all
      treated by coronoidectomy and appropriate physiotherapy. An improvement in mouth
      opening could be achieved in 86% of our patients. CONCLUSIONS: In comparison to
      the somewhat disappointing results of previously published studies with regard to
      mouth opening and mandibular mobility, our treatment concept seems to offer the
      possibility for improvement. Our study emphasizes the significance of three
      dimensional CT techniques for diagnosis and surgical planning, the superiority of
      coronoidectomy over coronoidotomy, and the importance of dynamic physiotherapy to
      prevent postoperative scar formation.

PMID- 17028845
TI  - [Effects of nicotine with special consideration given to tumorigenesis in the
      head and neck region].
AB  - BACKGROUND: Tumorigenesis is based on initiation, promotion, and progression,
      whereas tobacco smoke is a decisive predisposing factor for squamous cell
      carcinomas of the upper aerodigestive tract. A variety of tobacco smoke compounds
      is known to potentially initiate tumors, but the alkaloid nicotine is generally
      considered to induce addiction only. However, there is growing evidence that
      nicotine may also contribute to early stages of tumorigenesis. In the present
      study, a possible direct genotoxic potential of nicotine is investigated.
      MATERIAL AND METHODS: Lymphatic tissue of the tonsilla palatina of eight donors
      was harvested during surgery and incubated with nicotine. DNA damage was measured
      with the comet assay. RESULTS: Genotoxic effects of nicotine could be
      demonstrated. DISCUSSION: The results suggest a direct contribution of nicotine
      to tumor initiation and carcinogenesis.

PMID- 17028847
TI  - Protein kinase C isoforms from Giardia duodenalis: identification and functional
      characterization of a beta-like molecule during encystment.
AB  - Protein kinase C (PKC) is a family of serine/threonine kinases that regulate many
      different cellular processes such as cell growth and differentiation in
      eukaryotic cells. Using specific polyclonal antibodies raised against mammalian
      PKC isoforms, it was demonstrated here for the first time that Giardia duodenalis
      expresses several PKC isoforms (beta, delta, epsilon, theta and zeta). All PKC
      isoforms detected showed changes in their expression pattern during encystment
      induction. In addition, selective PKC inhibitors blocked the encystment in a dose
      dependent manner, suggesting that PKC isozymes may play important roles during
      this differentiation process. We have characterized here the only conventional
      type PKC member found so far in Giardia, which showed an increased expression and
      changes in its intracellular localization pattern during cyst formation. The
      purified protein obtained by chromatography on DEAE-cellulose followed by size
      exclusion chromatography, displayed in vitro kinase activity using histone HI
      IIIS as substrate, which was dependent on cofactors required by conventional
      PKCs, i.e., phospholipids and calcium. An open reading frame in the Giardia
      Genome Database that encodes a homolog of PKCbeta catalytic domain was identified
      and cloned. The expressed recombinant protein was also recognized by a mammalian
      anti-PKCbeta antibody and was referred as giardial PKCbeta on the basis of all
      these experimental evidence.

PMID- 17028846
TI  - Urinary F2-isoprostane metabolite levels in children with sleep-disordered
      breathing.
AB  - Oxidant stress-related mechanisms have been proposed as a major contributor to
      the increased prevalence of cardiovascular morbidity in adult patients with sleep
      disordered breathing. Isoprostanes provide a reliable biomarker of oxidant injury
      in vivo. The purpose of the present study was to examine the hypothesis that
      oxidant stress, as evidenced by increased levels of F2-isoprostane metabolites
      (IsoP-m) in urine, is present in children with a spectrum of sleep-disordered
      breathing. Assays were performed on urinary samples obtained from each of 47
      pediatric patients immediately upon awakening after standard overnight
      polysomnography. Of the subjects, 15% had mild, 9% had moderate, and 6% had
      severe sleep-disordered breathing. After controlling for correlations between BMI
      and IsoP-m and SpO2 values, IsoP-m values were unrelated to any polysomnographic
      measures. The absence of increased levels of urinary F2-isoprostane metabolites
      in children with sleep-disordered breathing suggests that oxidative stress is not
      a significant feature of pediatric sleep-disordered breathing.

PMID- 17028848
TI  - Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+
      influx through a vanilloid receptor-independent pathway in bovine adrenal
      medullary cells.
AB  - We report here the effects of capsaicin, a flavoring ingredient in the hot pepper
      Capsicum family, on catecholamine secretion and synthesis in cultured bovine
      adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5,
      11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic
      acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+)
      channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels,
      respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx
      (IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced
      (22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM),
      and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in
      catecholamine secretion caused by capsaicin was not overcome by increasing the
      concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive
      antagonist for the transient receptor potential vanilloid 1, and ruthenium red
      (30 microM), a nonselective cation channel antagonist, did not block the
      inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed
      both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6
      and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4
      dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase
      activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest
      that capsaicin inhibits catecholamine secretion and synthesis via suppression of
      Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.

PMID- 17028850
TI  - Compositional and technological features of glazed pottery from Aosta Valley
      (Italy): a SEM-EDS investigation.
AB  - Twelve finds from archaeological excavations carried out in the Aosta region
      (Italy) were studied by scanning electron microscopy coupled with energy
      dispersive X-ray detection (SEM-EDS). The archaeological samples were shards of
      glazed pottery dating from the fourth to the seventh century AD. Analysis of
      ceramic bodies revealed a general homogeneity in composition among the studied
      samples and the use of a noncalcareous clay for their manufacture; however, two
      shards stand out due to their high iron contents. Glazes proved to be high-lead
      products with more than 70% PbO in all of the samples investigated but one. For
      the latter, a composition poorer in lead and richer in silicon, aluminium and
      iron was found. SEM observation of the contact region between body and glaze
      suggests that the vitreous coatings were mostly obtained by applying the glazing
      components onto the unfired clay body; moreover, a comparison between clay and
      glaze compositions suggests the use of a lead compound mixed with a silica-rich
      material, not a lead compound by itself.

PMID- 17028849
TI  - Comparison of three radioligands for the labelling of human beta-adrenoceptor
      subtypes.
AB  - We have compared the ability of three radioligands, [(125)I]-cyanopindolol,
      [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol, to label the three human beta
      adrenoceptor subtypes. Saturation and competition binding experiments were
      performed using membrane preparations from Chinese hamster ovary cells stably
      transfected with the three subtypes. While [(3)H]-CGP 12,177 had very similar
      affinity for beta(1)- and beta(2)-adrenoceptors (about 40 pM), [(125)I]
      cyanopindolol and [(3)H]-dihydroalprenolol had 4- to 6-fold higher affinity for
      beta(2)- as compared to beta(1)-adrenoceptors (10 vs 45 and 187 vs 1,021 pM,
      respectively). The affinity of [(125)I]-cyanopindolol at beta(3)-adrenoceptors
      was considerably lower (440 pM) than at the other two subtypes. The beta(3)
      adrenoceptor affinity of [(3)H]-CGP 12,177 and [(3)H]-dihydroalprenolol was so
      low that it could not be estimated within the tested range of radioligand
      concentrations (up to 4,000 pM and 30,000 pM for [(3)H]-CGP 12,177 and [(3)H]
      dihydroalprenolol, respectively). We conclude that all three radioligands are ill
      suited to label beta(3)-adrenoceptors, particularly in preparations co-expressing
      multiple subtypes. In the absence of alternatives, [(125)I]-cyanopindolol appears
      the least unsuitable to label beta(3)-adrenoceptors. There is a need for high
      affinity radioligands which are either selective for beta(3)-adrenoceptors or
      reasonably non-selective among all three beta-adrenoceptor subtypes.

PMID- 17028852
TI  - Sonographic diagnosis of a common pancreaticobiliary channel in children.
AB  - BACKGROUND: A common pancreaticobiliary channel is a very rare condition, but its
      diagnosis is of paramount importance since it can lead to complications that can
      be prevented. OBJECTIVE: To illustrate the sonographic diagnosis of a common
      pancreaticobiliary channel in children referred for abdominal pain or jaundice.
      MATERIALS AND METHODS: Four children were diagnosed by ultrasonography and the
      diagnosis was subsequently confirmed by MRI. RESULTS: Sonography demonstrated a
      pancreaticobiliary junction located in the pancreatic head above the sphincter of
      Oddi. This rare congenital anomaly was confirmed in all patients by MRI.
      CONCLUSION: A common pancreaticobiliary channel can be diagnosed by sonography.
      Nevertheless, our experience is limited, and although sonography can provide an
      alert and can assist management, it cannot yet replace MRI.

PMID- 17028853
TI  - Diagnostic performance of MRI and MR myelography in infants with a brachial
      plexus birth injury.
AB  - BACKGROUND: Detailed evaluation of a brachial plexus birth injury is important
      for treatment planning. OBJECTIVE: To determine the diagnostic performance of MRI
      and MR myelography in infants with a brachial plexus birth injury. MATERIALS AND
      METHODS: Included in the study were 31 children with perinatal brachial plexus
      injury who underwent surgical intervention. All patients had cervical and
      brachial plexus MRI. The standard of reference was the combination of
      intraoperative (1) surgical evaluation and (2) electrophysiological studies
      (motor evoked potentials, MEP, and somatosensory evoked potentials, SSEP), and
      (3) the evaluation of histopathological neuronal loss. MRI findings of cord
      lesion, pseudomeningocele, and post-traumatic neuroma were correlated with the
      standard of reference. Diagnostic performance characteristics including
      sensitivity and specificity were determined. RESULTS: From June 2001 to March
      2004, 31 children (mean age 7.3 months, standard deviation 1.6 months, range 4.8
      12.1 months; 19 male, 12 female) with a brachial plexus birth injury who
      underwent surgical intervention were enrolled. Sensitivity and specificity of an
      MRI finding of post-traumatic neuroma were 97% (30/31) and 100% (31/31),
      respectively, using the contralateral normal brachial plexus as the control.
      However, MRI could not determine the exact anatomic area (i.e. trunk or division)
      of the post-traumatic brachial plexus neuroma injury. Sensitivity and specificity
      for an MRI finding of pseudomeningocele in determining exiting nerve injury were
      50% and 100%, respectively, using MEP, and 44% and 80%, respectively, using SSEP
      as the standard of reference. MRI in infants could not image well the exiting
      nerve roots to determine consistently the presence or absence of definite
      avulsion. CONCLUSION: In children younger than 18 months with brachial plexus
      injury, the MRI finding of pseudomeningocele has a low sensitivity and a high
      specificity for nerve root avulsion. MRI and MR myelography cannot image well the
      exiting nerve roots to determine consistently the presence or absence of avulsion
      of nerve roots. The MRI finding of post-traumatic neuroma has a high sensitivity
      and specificity in determining the side of the brachial plexus injury but cannot
      reveal the exact anatomic area (i.e. trunk or division) involved. The information
      obtained is, however, useful to the surgeon during intraoperative evaluation of
      spinal nerve integrity for reconstruction.

PMID- 17028855
TI  - Strain-dependent expression of four structurally related rat Ly49 receptors;
      correlation with NK gene complex haplotype and NK alloreactivity.
AB  - Natural killer (NK) cells from certain rat strains promptly kill MHC allogeneic
      lymphocytes in vivo, a rejection phenomenon termed allogeneic lymphocyte
      cytotoxicity (ALC). ALC can be reproduced in vitro, and is preferentially
      mediated by a subset of NK cells expressing the Ly49 stimulatory receptor 3
      (Ly49s3) in PVG strain rats. Functional studies have suggested that Ly49s3
      triggers NK cell alloreactivity, but its importance relative to other Ly49
      receptors has not been investigated. In this study, we have characterized three
      rat Ly49 receptors with close sequence similarity to Ly49s3 in the extracellular
      region, i.e., Ly49s4, Ly49 inhibitory receptor 3 (Ly49i3), and Ly49i4. Similar to
      Ly49s3, Ly49s4 mediated cellular activation while Ly49i4 inhibited NK cytolytic
      function. Ly49s4, -i3, and -i4 all reacted with a previously described anti
      Ly49s3 monoclonal antibody (mAb) (DAR13), but not a novel mAb (STOK6), which was
      shown to be specific for Ly49s3. Expression of these Ly49 receptors varied
      markedly between inbred strains, in patterns related to their NK gene complex
      (NKC) haplotype, and ability to mediate ALC. Three major groups of NKC haplotypes
      could be discerned by restriction fragment length polymorphism analysis. Ly49s3
      was present in strains from one of the groups, which corresponded with the "high"
      ALC responders. Ly49s3 surface expression was also markedly reduced in the
      presence of its putative MHC class Ib ligand(s) in MHC congenic strains. These
      data support the notion that Ly49s3 functions as a triggering MHC receptor both
      in vitro and in vivo. MHC ligands for the other three Ly49 receptors remain to be
      determined.

PMID- 17028856
TI  - Two factor H-related proteins from the mouse: expression analysis and functional
      characterization.
AB  - Complement factor H-related (FHR) proteins display structural and functional
      similarities to each other and to the complement regulator factor H (FH). FHRs
      have been identified in various species, including human, rat, and the fish
      barred sand bass. As mice provide a useful model system to study the
      physiological role of FHRs in vivo, we aimed at characterizing murine FHR
      proteins. Two putative FHRs of approximately 100 and 38 kDa were detected in
      mouse plasma using FH-specific antiserum. In a liver cDNA library, three murine
      FHR-encoding transcripts were identified. Two clones code for related FHR
      proteins termed FHR-C and FHR-C_v1, which in secreted form are composed of 14 and
      13 short consensus repeat (SCR) domains, homologous to SCRs 6-17 and 19-20 of FH.
      The third transcript, FHR-B, is derived from a separate gene and codes for a
      secreted protein composed of five SCR domains. FHR-B displays homology to SCRs 5
      7 and 19-20 of FH. Expression of FHR-B in various tissues was analyzed by real
      time polymerase chain reaction and was identified at high levels in liver, kidney
      and heart. In liver, FHR-B transcript level was even higher than that of FH. In
      addition, FHR-B was expressed as a recombinant 37-kDa protein, and this
      recombinant FHR-B interacted with the ligands heparin and human C3b. Using mouse
      plasma, the native presumptive FHR proteins were also analyzed in binding assays.
      In summary, we identify two FHR proteins in mice and for the first time
      characterize a murine FHR as a heparin- and C3b-binding protein.

PMID- 17028857
TI  - Radiological and functional assessment of pulmonary involvement in the rheumatoid
      arthritis patients.
AB  - The aim was to evaluate the findings of high resolution computed tomography
      (HRCT) and pulmonary function tests (PFT) in the rheumatoid arthritis (RA)
      patients with and without pulmonary symptoms and to determine their role in
      prediction of respiratory system involvement. Among 54 consecutive RA patients,
      22 (41%) were symptomatic and 32 (59%) were asymptomatic after detailed
      respiratory examination. Abnormal findings in PFTs were present in 10 (45%)
      symptomatic and 15 (47%) asymptomatic patients. PFT results were similar in both
      groups. A total of 18 (82%) symptomatic and 16 (50%) asymptomatic patients had
      abnormalities in HRCT scans. About 16 (80%) of 20 patients with normal HRCT scans
      had no pulmonary symptoms at all and we noted a significant correlation (P <
      0.05). HRCT was more useful mean than PFTs in evaluation of pulmonary involvement
      in the RA patients; however, no correlation was present between various
      respiratory symptoms and abnormal findings both in PFTs and HRCT scans.

PMID- 17028858
TI  - Enhanced oxidative status but not corresponding elevated antioxidative status by
      anticardiolipin antibody and disease activity in patients with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis,
      and an increased susceptibility of plasma lipids and lipoproteins to oxidation
      could at least in part promote atherogenesis. The objective of this study was to
      identify the effects of anticardiolipin antibody (aCL) and disease activity on
      oxidative and antioxidative status in patients with SLE. In this study, patients
      in SLE/aCL+ group and in SLE disease activity index >3 group had significantly
      higher thiobarbituric acid reactive substance (TBARS) levels, titers of
      autoantibodies against oxidized low-density lipoprotein (ox-LDL), and glutathione
      peroxidase activity than that of healthy controls. However, only TBARS and titers
      of autoantibodies against ox-LDL but not antioxidant enzyme activities were
      significantly different between SLE subgroups. Thus, enhanced oxidative status
      but not corresponding elevated antioxidative status by the presence of aCL and
      active disease activity make potent antioxidant therapy valuable for these SLE
      patients in preventing oxidative damage.

PMID- 17028859
TI  - Which of the three different tender points assessment methods is more useful for
      predicting the severity of fibromyalgia syndrome?
AB  - Digital palpation, myalgic scoring and dolorimetry are frequently used to count
      tender points in fibromyalgia syndrome. We aimed to investigate the probable
      relation between tender points count and fibromyalgia impact questionnaire and to
      assess which of the tender point counting methods is the most successful in
      predicting the severity of the disease. Tender point areas of 36 patients with
      fibromyalgia syndrome were assessed with three methods which are myalgic scoring,
      digital and dolorimetric tender points counting methods. Fibromyalgia impact
      questionnaire was used to measure the disease severity. The correlation between
      each of the assessment methods and fibromyalgia impact questionnaire was
      investigated. The mean count of digitally evaluated tender points was 14.86 +/-
      2.67 and by dolorimetry was 11.81 +/- 4.48. The mean total myalgic score was
      found to be 24.61 +/- 8.91. All of the tender point evaluation methods correlated
      positively with each other (P < 0.01). Fibromyalgia impact questionnaire score
      was also correlated with only digital palpation tender point count of these three
      evaluation methods (r = 0.427, P < 0.05). Digital tender point count seemed to be
      sufficient for assessment, and there is no need for an additional instrument for
      tender point evaluation.

PMID- 17028860
TI  - A case of pure red cell aplasia and systemic lupus erythematosus caused by human
      parvovirus B19 infection.
AB  - Human parvovirus B19 (B19) rarely induces pure red cell aplasia (PRCA) in healthy
      hosts. Meanwhile B19 infection is often clinically similar to systemic lupus
      erythematosus (SLE), and several cases have been reported wherein B19 actually
      stimulated SLE exacerbation in an immunocompetent subject. An 82-year-old healthy
      woman was diagnosed to have complicated with B19 infection and PRCA. Four weeks
      later, she had high fever, polyarthritis, and oral ulcers, additionally diagnosed
      with SLE, and subsequently, 15 mg of prednisone was started. This is the first
      case wherein B19 infection caused both PRCA and SLE in a healthy patient as far
      as our investigations are concerned.

PMID- 17028861
TI  - MRI in psoriatic arthritis with hand and foot involvement.
AB  - Evaluation of MRI-findings in patients with involvement of psoriatic arthritis
      (PsA) in small joints in hands and feet. Twenty-five patients with symptomatic
      joint involvement were studied by MRI. All patients were found to be positive for
      one or more imaging criteria. Soft tissue oedema was identified in 22/25 (88%)
      patients. Joint effusion was observed in 23/25 (92%) patients, whereas bone
      erosion was seen in 20/25 (80%) patients. Bone marrow oedema was evident in 21/25
      (84%) cases. In 12/25 (48%) cases, bone proliferation was noted. Tendon sheath
      effusion was present in 17/25 (68%) patients. Contrast enhancement of the synovia
      was detected in all patients (n = 25) (100%), whereas adjacent periost was
      enhanced in 22/25 (88%) and epiphysial bone marrow in 18/25 (72%) patients. MRI
      allows the assessment of PsA-alterations of soft tissue, cartilage, bone, bone
      marrow, and adjacent tendon sheath in patients with hand and foot involvement.

PMID- 17028862
TI  - The incidence of new onset congestive heart failure and heart failure
      exacerbation in Veteran's Affairs patients receiving tumor necrosis factor alpha
      antagonists.
AB  - The objective of this study was to evaluate the incidence of new onset or
      worsening congestive heart failure in Veteran's Affairs (VA) patients who have
      received infliximab, etanercept, or adalimumab, and to compare mortality rates in
      these patients to control populations. We enrolled three groups of patients for
      this retrospective study: TNF-alpha group (n = 103), a rheumatoid arthritis (RA)
      control group (n = 100), and a control group without RA (n = 100). All patients
      at our VA facility who had received at least one dose of the TNF-alpha
      antagonists were included in the TNF-alpha group. Admissions for CHF did not
      differ between the three groups: TNF-alpha 7 (6.7%), RA control 8 (8%), non-RA
      control 7 (7%); P = 0.940. Mortality rates were not significantly different: TNF
      alpha 4 (3.8%), RA control 7 (7%), non-RA control 11 (11%); P = 0.147. Our study
      showed no difference between the three groups in either CHF exacerbation or
      mortality.

PMID- 17028863
TI  - Matrix metalloproteinases and their inhibitors in the chamber angle of normal
      eyes and patients with primary open-angle glaucoma and exfoliation glaucoma.
AB  - BACKGROUND: In glaucoma, extensive pathological changes occur in the trabecular
      meshwork (TM) and juxtacanalicular tissue of the chamber angle. Aqueous humor
      drainage is disturbed due to the accumulation of extracellular matrix (ECM)
      material in the outflow system. Matrix metalloproteinases (MMPs) remodel ECM
      material and, thus, they may have a role in regulating outflow facility and
      intraocular pressure (IOP). This study examined the expression of MMPs and tissue
      inhibitors of MMPs (TIMPs) in the chamber angle of normal eyes and in primary
      open-angle glaucoma (POAG) and in exfoliation glaucoma (ExG). METHODS: TM tissues
      were isolated from healthy donor eyes for corneal transplantation. Specimens of
      the inner wall of Schlemm's canal and the juxtacanalicular tissue were collected
      from patients with POAG or ExG during deep sclerectomy operation. Monoclonal
      antibodies against MMPs (MMP-1, -2, -3, and -9) and antibodies against TIMPs
      (TIMP-1, -2, and -3) were used for immunohistochemical staining. RESULTS:
      Immunoreactivity for MMP-2, TIMP-2, or TIMP-3 was observed in human normal TM and
      in the inner wall of Schlemm's canal. In general, immunoreactions for all of the
      tested MMPs were more intense in POAG samples than in ExG samples or in the
      control group. The only exception was the MMP-2 level, which was the highest in
      the control group. The staining intensity of MMP-1 or MMP-3 was significantly
      higher in POAG when compared to ExG. TIMP-1 was significantly increased in POAG
      compared with ExG and there were no marked differences in the levels of TIMP-2 or
      TIMP-3 between POAG and ExG. The ratios of MMP-1/TIMP-1 and MMP(1+2+3+9) and
      TIMP(1+2+3) were significantly higher in samples from POAG compared to those of
      ExG. CONCLUSIONS: Our results reveal an expression imbalance between MMPs and
      their endogenous tissue inhibitors in tissue samples from patients with POAG and
      ExG. Differences in immunohistochemical reactions reflect discrete local
      pathogenic mechanisms involved in POAG and ExG. With respect to the proposed role
      of MMPs in the remodeling of ECM material, this may point to a weaker reactivity
      to the accumulation of ECM material in TM in ExG than POAG eyes.

PMID- 17028865
TI  - Bayesian data mining of protein domains gives an efficient predictive algorithm
      and new insight.
AB  - Identification of structural domains in uncharacterized protein sequences is
      important in the prediction of protein tertiary folds and functional sites, and
      hence in designing biologically active molecules. We present a new predictive
      computational method of classifying a protein into single, two continuous or two
      discontinuous domains using Bayesian Data Mining. The algorithm requires only the
      primary sequence and computer-predicted secondary structure. It incorporates
      correlation patterns between certain 3-dimensional motifs and some local helical
      folds found conserved in the vicinity of protein domains with high statistical
      confidence. The prediction of domain-class by this computationally simple and
      fast method shows good accuracy of prediction-average accuracies 83.3% for single
      domain, 60% for two continuous and 65.7% for two discontinuous domain proteins.
      Experiments on the large validation sample show its performance to be
      significantly better than that of DGS and DomSSEA. Computations of Bayesian
      probabilities show important features in terms of correlation of certain
      conserved patterns of secondary folds and tertiary motifs and give new insight.
      Applications for improved accuracy of predicting domain boundary points relevant
      to protein structural and functional modeling are also highlighted.

PMID- 17028864
TI  - Molecular characterization of deletion breakpoints in adults with 22q11 deletion
      syndrome.
AB  - 22q11 Deletion syndrome (22q11DS) is a common microdeletion syndrome with
      variable expression, including congenital and later onset conditions such as
      schizophrenia. Most studies indicate that expression does not appear to be
      related to length of the deletion but there is limited information on the
      endpoints of even the common deletion breakpoint regions in adults. We used a
      real-time quantitative PCR (qPCR) approach to fine map 22q11.2 deletions in 44
      adults with 22q11DS, 22 with schizophrenia (SZ; 12 M, 10 F; mean age 35.7 SD 8.0
      years) and 22 with no history of psychosis (NP; 8 M, 14 F; mean age 27.1 SD 8.6
      years). QPCR data were consistent with clinical FISH results using the TUPLE1 or
      N25 probes. Two subjects (one SZ, one NP) negative for clinical FISH had atypical
      22q11.2 deletions confirmed by FISH using the RP11-138C22 probe. Most (n = 34; 18
      SZ, 16 NP) subjects shared a common 3 Mb hemizygous 22q11.2 deletion. However,
      eight subjects showed breakpoint variability: a more telomeric proximal
      breakpoint (n = 2), or more centromeric (n = 3) or more telomeric distal
      breakpoint (n = 3). One NP subject had a proximal nested 1.4 Mb deletion. COMT
      and TBX1 were deleted in all 44 subjects, and PRODH in 40 subjects (19 SZ, 21
      NP). The results delineate proximal and distal breakpoint variants in 22q11DS.
      Neither deletion extent nor PRODH haploinsufficiency appeared to explain the
      clinical expression of schizophrenia in the present study. Further studies are
      needed to elucidate the molecular basis of schizophrenia and clinical
      heterogeneity in 22q11DS.

PMID- 17028866
TI  - Severe metallosis after unicompartmental knee arthroplasty.
AB  - We report on a case of a patient who had femoral osteolysis and severe metallosis
      of the knee joint resulting from the secondary abrasive wear of the metal-backed
      tibial component of a unicompartmental knee arthroplasty due to massive wear of
      tibial polyethylene. The failure was diagnosed 11 years after implantation. This
      metallosis affected the intra-articular tissues and the subchondral bone.

PMID- 17028867
TI  - Sclerosing polidocanol injections to treat chronic painful shoulder impingement
      syndrome-results of a two-centre collaborative pilot study.
AB  - The histological changes found in the supraspinatus tendon have similarities with
      the findings in Achilles-, patellar- and extensor carpi radialis brevis (ECRB)
      tendinopathy. In recent studies, we have found a vasculo-neural ingrowth in
      chronic painful Achilles and patellar tendinopathy, and demonstrated good short
      term clinical effects with injections of the sclerosing substance polidocanol. In
      this collaborative two-centre pilot study, 15 patients (10 males and 5 females,
      mean age 46 years) with a long duration of shoulder pain (mean 28 months), and
      given the diagnosis chronic painful shoulder impingement syndrome, were included.
      They had tried rest, traditional rehabilitation exercises and multiple
      subacromial corticosteroid injections, without effect. We found vascularity
      (neovessels) in chronic painful, but not in pain-free, supraspinatus tendons, and
      prospectively studied the clinical effects of ultrasound (US) and colour Doppler
      (CD)-guided injections of polidocanol, targeting the area with neovessels. The
      patients evaluated the amount of shoulder pain during horizontal shoulder
      activity on a visual analogue scale (VAS), and satisfaction with treatment. Two
      (median) (range 1-5) polidocanol treatments (with 4-8 weeks in between) were
      given. In four patients (considered treatment failure), cortisone was injected
      into an inflamed subacromial bursa at one separate occasion weeks after the last
      polidocanol injection. At follow-up, 8 (median) (range 4-17) months after the
      treatment, 14 patients were satisfied with the result. Using the visual analogue
      scale evaluation (VAS), the pain dropped from 79 before treatment to 21 at follow
      up (P < 0.05). In the short-term perspective, sclerosing polidocanol injections
      targeting the neovessels in the supraspinatus tendon and/or bursa wall seems to
      have a potential to reduce the pain during shoulder loading activity.

PMID- 17028868
TI  - The Oxford phase III unicompartmental knee replacement in patients less than 60
      years of age.
AB  - Treatment of younger patients with medial unicompartmental disease of the knee
      joint remains a challenging therapeutic dilemma. With the refinement of implant
      design, fixation and the minimally invasive techniques employed with
      unicompartmental knee replacement, indications have expanded to include its use
      in young patients. A prospective cohort of 46 unicompartmental knee procedures
      were performed with a 2-year minimum and 6-year maximum follow-up, using the
      Oxford phase III unicompartmental knee arthroplasty, in the younger patient group
      (age 60 or younger). We conclude that the unicompartmental knee arthroplasty is
      an important option for the treatment of medial compartment disease for patients
      60 years or younger. Obesity can cause technical difficulties, increased risk of
      complications and early failure of this prosthesis.

PMID- 17028869
TI  - Second-look arthroscopic findings of 208 patients after ACL reconstruction.
AB  - The aim of this study is to report the arthroscopic subjective findings of
      reconstructed anterior cruciate ligament (ACL) with good clinical outcome. Graft
      used for reconstruction was either patella bone-tendon-bone (PBTB) autograft or
      hamstring tendon [quadrupled semitendinous and gracilis tendon (QSGT)] autograft.
      From March 1997 to September 2003, among 716 ACL reconstructions 209 knees (208
      patients) were available for second-look arthroscopy at a mean 21.2-month (range,
      14-70 months) postoperative period. The second-look arthroscopy focused on the
      evaluation of (1) continuity of the reconstructed ACL graft, (2) subjective graft
      tension using a probe, (3) the extent of synovial coverage, (4) the prevalence of
      cyclops or cyclops-like lesion, and (5) bony change after notchplasty. Patellar
      tendon autograft was used in 80 knees, hamstring tendon autograft in 129 knees.
      Just prior to second-look arthroscopy two objective clinical evaluations, KT-2000
      arthrometer and Lysholm knee score, were performed to verify good clinical
      outcomes. A comparison between the hamstring tendon group and the patella tendon
      group, hamstring group showed slightly better results in Lysholm knee scores and
      KT-2000 arthrometer but there were no statistically significant differences
      (p>0.05). Undetected partial graft tear was seen in 21 knees (10%). With regard
      to graft tension, a total of 181 grafts (87%) showed normal tension and 28 (13%)
      showed slight lax tension. The overall synovial coverage was poor in nine (4%)
      knees. The synovial coverage was slightly better in the hamstring tendon group. A
      total of 45 knees (21.5%) showed cyclops-like lesion in variable sizes and
      locations. Reformation of the notch was seen in 85 knees (40%). In conclusion,
      the findings of second-look arthroscopy of reconstructed ACL in good clinical
      outcome patients showed approximately 10% partial graft tear, 5% poor synovial
      coverage, 20% cyclops-like lesion, and 40% some notch reformation.

PMID- 17028870
TI  - Distribution of extracellular polymeric substances in aerobic granules.
AB  - Extracellular matrix provides an architectural structure and mechanical stability
      for aerobic granules. Distributions of cells and extracellular polymeric
      substances (EPS), including proteins, alpha- and beta-D-glucopyranose
      polysaccharides, in acetate-fed granules and phenol-fed granules were probed
      using a novel quadruple staining scheme. In acetate-fed granules, protein and
      beta-D-glucopyranose polysaccharides formed the core, whereas, the cells and
      alpha-D-glucopyranose polysaccharides accumulated in the granule outer layers.
      Based on these experimental findings, this study indicated that different
      conclusions can be obtained regarding EPS distributions when granules were
      stained differently. The core of phenol-fed granules, conversely, was formed
      principally by proteins; whereas, the cells and alpha- and beta-D-glucopyranose
      polysaccharides were accumulated at an outer filamentous layer. Using a series of
      confocal laser scanning microscope (CLSM) images whose threshold values were
      determined via Otsu's scheme, the three-dimensional distributions of cells and
      EPS were produced using a polygonal surface model. Structural information
      extracted can be applied in further development of comprehensive granule models.

PMID- 17028871
TI  - Expression and secretion of a single-chain sweet protein monellin in Bacillus
      subtilis by sacB promoter and signal peptide.
AB  - The sweet protein monellin gene was expressed in Bacillus subtilis under the
      control of the Bacillus subtilis sacB promoter and signal peptide sequence. A 294
      bp DNA fragment, coding for sweet protein monellin, was ligated into the
      Escherichia coli/B. subtilis shuttle vector pHPC, producing pHPMS, which was
      subsequently transformed into B. subtilis QB1098, DB104, and DB403. The peptide
      efficiently directed the secretion of monellin from the recombinant B. subtilis
      cells. A maximum yield of monellin of 0.29 g protein l(-1) was obtained from the
      supernatant of B. subtilis DB403 harboring pHPMS. SDS-PAGE confirmed the purity
      of the recombinant product.

PMID- 17028872
TI  - Synthesis of DL-tryptophan by modified broad specificity amino acid racemase from
      Pseudomonas putida IFO 12996.
AB  - Broad specificity amino acid racemase (E.C. 5.1.1.10) from Pseudomonas putida IFO
      12996 (BAR) is a unique racemase because of its broad substrate specificity. BAR
      has been considered as a possible catalyst which directly converts inexpensive L
      amino acids to DL-amino acid racemates. The gene encoding BAR was cloned to
      utilize BAR for the synthesis of D-amino acids, especially D-Trp which is an
      important intermediate of pharmaceuticals. The substrate specificity of cloned
      BAR covered all of the standard amino acids; however, the activity toward Trp was
      low. Then, we performed random mutagenesis on bar to obtain mutant BAR
      derivatives with high activity for Trp. Five positive mutants were isolated after
      the two-step screening of the randomly mutated BAR. After the determination of
      the amino acid substitutions in these mutants, it was suggested that the
      substitutions at Y396 and I384 increased the Trp specific racemization activity
      and the racemization activity for overall amino acids, respectively. Among the
      positive mutants, I384M mutant BAR showed the highest activity for Trp. L-Trp (20
      mM) was successfully racemized, and the proportion of D-Trp was reached 43% using
      I384M mutant BAR, while wild-type BAR racemized only 6% of initial L-Trp.

PMID- 17028873
TI  - Methanol utilizing Desulfotomaculum species utilizes hydrogen in a methanol-fed
      sulfate-reducing bioreactor.
AB  - A sulfate-reducing bacterium, strain WW1, was isolated from a thermophilic
      bioreactor operated at 65 degrees C with methanol as sole energy source in the
      presence of sulfate. Growth of strain WW1 on methanol or acetate was inhibited at
      a sulfide concentration of 200 mg l(-1), while on H2/CO2, no apparent inhibition
      occurred up to a concentration of 500 mg l(-1). When strain WW1 was co-cultured
      under the same conditions with the methanol-utilizing, non-sulfate-reducing
      bacteria, Thermotoga lettingae and Moorella mulderi, both originating from the
      same bioreactor, growth and sulfide formation were observed up to 430 mg l(-1).
      These results indicated that in the co-cultures, a major part of the electron
      flow was directed from methanol via H2/CO2 to the reduction of sulfate to
      sulfide. Besides methanol, acetate, and hydrogen, strain WW1 was also able to use
      formate, malate, fumarate, propionate, succinate, butyrate, ethanol, propanol,
      butanol, isobutanol, with concomitant reduction of sulfate to sulfide. In the
      absence of sulfate, strain WW1 grew only on pyruvate and lactate. On the basis of
      16S rRNA analysis, strain WW1 was most closely related to Desulfotomaculum
      thermocisternum and Desulfotomaculum australicum. However, physiological
      properties of strain WW1 differed in some aspects from those of the two related
      bacteria.

PMID- 17028874
TI  - Genomic adaptation of ethanologenic yeast to biomass conversion inhibitors.
AB  - One major barrier to the economic conversion of biomass to ethanol is inhibitory
      compounds generated during biomass pretreatment using dilute acid hydrolysis.
      Major inhibitors such as furfural and 5-hydroxymethylfurfural (HMF) inhibit yeast
      growth and subsequent fermentation. The ethanologenic yeast Saccharomyces
      cerevisiae demonstrated a dose-dependant inhibition by the inhibitors and has the
      potential to transform furfural and HMF into less toxic compounds of furfuryl
      alcohol and 2,5-bis-hydroxymethylfuran (also termed as furan-2,5-dimethanol
      (FDM)), respectively. For a sustainable and cost-competitive biomass-to-ethanol
      industry, it is important to develop more tolerant yeast strains that can, in
      situ, detoxify the inhibitors and produce ethanol. This study summarizes current
      knowledge and our understanding of the inhibitors furfural and HMF and discusses
      metabolic conversion pathways of the inhibitors and the yeast genomic expression
      response to inhibitor stress. Unlike laboratory strains, gene expression response
      of the ethanologenic yeast to furfural and HMF was not transient, but a continued
      dynamic process involving multiple genes at the genome level. This suggests that
      during the lag phase, ethanologenic yeasts undergo a genomic adaptation process
      in response to the inhibitors. The findings to date provide a strong foundation
      for future studies on genomic adaptation and manipulation of yeast to aid more
      robust strain design and development.

PMID- 17028875
TI  - Monoterpenes as novel substrates for oxidation and halo-hydroxylation with
      chloroperoxidase from Caldariomyces fumago.
AB  - Chloroperoxidase (CPO) from Caldariomyces fumago was analysed for its ability to
      oxidize ten different monoterpenes with hydrogen peroxide as oxidant. In the
      absence of halide ions geraniol and, to a lesser extent, citronellol and nerol
      were converted into the corresponding aldehydes, whereas terpene hydrocarbons did
      not serve as substrates under these conditions. In the presence of chloride,
      bromide and iodide ions, every terpene tested was converted into one or more
      products. (1S)-(+)-3-carene was chosen as a model substrate for the CPO-catalysed
      conversion of terpenes in the presence of sodium halides. With chloride, bromide
      and iodide, the reaction products were the respective (1S,3R,4R,6R)-4-halo-3,7,7
      trimethyl-bicyclo[4.1.0]-heptane-3-ols, as identified by 1H and 13C nuclear
      magnetic resonance. These product formations turned out to be strictly regio- and
      stereoselective and proceeded very rapidly and almost quantitatively. Initial
      specific activities of halohydrin formation increased from 4.22 U mg-1 with
      chloride to 12.22 U mg-1 with bromide and 37.11 U mg-1 with iodide as the
      respective halide ion. These results represent the first examples of the
      application of CPO as a highly efficient biocatalyst for monoterpene
      functionalization. This is a promising strategy for 'green' terpene chemistry
      overcoming drawbacks usually associated with cofactor-dependent oxygenases, whole
      cell biocatalysts and conventional chemical methods used for terpene conversions.

PMID- 17028876
TI  - Biological nitrogen removal with nitrification and denitrification via nitrite
      pathway.
AB  - Presently, the wastewater treatment practices can be significantly improved
      through the introduction of new microbial treatment technologies. To meet
      increasingly stringent discharge standards, new applications and control
      strategies for the sustainable removal of ammonium from wastewater have to be
      implemented. Partial nitrification to nitrite was reported to be technically
      feasible and economically favorable, especially when wastewater with high
      ammonium concentrations or low C/N ratios is treated. For successful
      implementation of the technology, the critical point is how to maintain partial
      nitrification of ammonium to nitrite. Partial nitrification can be obtained by
      selectively inhibiting nitrite oxidizing bacteria through appropriate regulation
      of the system's DO concentration, microbial SRT, pH, temperature, substrate
      concentration and load, operational and aeration pattern, and inhibitor. The
      review addressed the microbiology, its consequences for their application, the
      current status regarding application, and the future developments.

PMID- 17028877
TI  - Production of red mold rice using a modified Nagata type koji maker.
AB  - In this research, a commercial koji maker with a rotary perforated bed of 5-m
      diameter was modified for red mold rice production. Monascus purpureus BCRC 31499
      was selected for its high production capacities of monacolin K and red pigment.
      The selected strain was first cultivated in a 120-l submerged type fermentor at
      34 degrees C and 2 vvm aeration rate with 60 rpm agitation for 5 days using 20%
      liquefied rice porridge as carbon source. The high concentration red mold rice
      broth (>3.5 g/ml) was harvested for inocula and well mixed with cooked rice to an
      initial concentration of 2% v/w. The inoculated cooked rice then was directed
      into the modified koji maker, in which temperature and humidity profiles were
      kept at varied levels at different stages, respectively. Air was circulated to
      remove fermentation heat while the perforated bed rotated slowly for providing
      mild agitation. Lag phase of the Monascus sp. in the modified koji maker was
      determined to be 16 h by the time the koji temperature raised rapidly. Water was
      added into the koji bed by a water curtain at the 36th hour to keep the moisture
      content of the rice koji at 50% or above. At the final stage, temperature was
      adjusted to 34 degrees C to direct red pigment production. After 7 days, 1,200-kg
      high quality red mold rice was harvested per batch. Labor costs, space, and
      fermentation time were reduced tremendously compared with those made by
      traditional methods.

PMID- 17028878
TI  - A case of split cord malformation associated with myeloschisis.
AB  - INTRODUCTION: Split cord malformation (SCM) associated with myeloschisis is a
      very rare form of spinal dysraphism. We encountered a case of SCM associated with
      myeloschisis showing split neural placodes (hemicords) in the upper lumbar
      region. RESULTS: Radiological examinations, including prenatal MRI and postnatal
      CT scan, clearly demonstrated a bony spur between the two hemicords as well as
      myeloschisis, which facilitated a precise preoperative diagnosis of this complex
      anomaly. Resection of the spur, closure of the myeloschisis, and untethering of
      the thickened filum terminale were successfully accomplished in one stage. The
      presence of SCM associated with myeloschisis is consistent with the hypothesis of
      an ontogenic basis of neural development, and we emphasize the importance of
      early imaging including prenatal MRI for diagnosing this complex anomaly.

PMID- 17028879
TI  - The Strata programmable valve for shunt-dependent hydrocephalus: the pediatric
      experience at a single institution.
AB  - BACKGROUND AND OBJECTIVE: The Medtronic PS Medical Strata valve has pressure flow
      characteristics that are noninvasively adjusted with a magnetic tool. The
      objective of this study was to examine its efficacy during our initial experience
      with it in shunt-dependent children. MATERIALS AND METHODS: A retrospective
      review of 53 children with a median age of 2.0 years who had 61 Strata valves
      implanted. CONCLUSION: The Strata valve is efficacious in the treatment of shunt
      dependant hydrocephalus in children. The 1-year shunt survival rate of 67.2% is
      comparable to that previously reported from a multicenter trial. Of the 30
      therapeutically aimed adjustments during the study period, 16 (53.3%) resulted in
      improvement in abnormal signs or symptoms. Our data indicate that adjustments can
      be used to treat signs or symptoms of cerebrospinal fluid overdrainage or
      underdrainage, which may obviate the need for additional surgery.

PMID- 17028880
TI  - Diastematomyelia in children: treatment outcome and natural history of associated
      syringomyelia.
AB  - OBJECTIVE: To quantify the long-term outcome of children with diastematomyelia
      and the implication of syringomyelia in the natural history. MATERIALS:
      Retrospective study of 17 children (nine girls and eight boys) with
      diastematomyelia operated during 1989-2004. Mean age at diagnosis was 3.4 years
      (range 5 days-12 years), mean follow-up was 5 years; 14 had excision of spur and
      cord untethering, 3 had excision of spur alone. RESULTS: The bony spur was in the
      lumbar region in 12 and thoracic in 5 patients. Syringomyelia was present in
      eight (47%), associated with bony spur between L1 and 4 (p=0.088), spina bifida
      occulta in ten (58.8%), and spinal lipoma in one (6%). Preoperative Necker
      Enfants Malades (NEM) scores were 17 in eight patients, 16 in four, 15 in three,
      13 in one, and 12 in one patient. Presenting neurological deficits were motor in
      eight, sensory deficits in three, and anal incontinence in one patient. There was
      improvement of NEM scores postoperatively in five patients only, but still with
      residual deficit. Repeat spur excision and cord untethering was performed in
      three patients for neurological deterioration 1-4 years after first operation. On
      postoperative MRI scans syringomyelia remained unchanged in all eight patients.
      There were one skin infection, one transient motor deterioration, and one patient
      with sensory deficit after surgery. CONCLUSION: Prophylactic operations were
      associated with the best clinical outcome. Despite improvement, all patients with
      established preoperative deficit still had residual neurological deficits at
      their last follow-up. The associated syringomyelia remained unchanged after
      surgery, indicating that it does not contribute to the neurological syndrome.

PMID- 17028881
TI  - Management of blunt tracheal trauma in children: a case series and review of the
      literature.
AB  - Blunt tracheal trauma seldom develops in children because of their anatomy and
      the mobility of the cartilage. It has the potential to be overlooked, either
      because of the severity of concomitant injuries or because of the unfamiliarity
      of paediatricians with this type of injury. However, tracheal injury might be
      lethal due to airway compromise. Early bronchoscopy may be necessary to
      anticipate complications and prevent permanent dysfunction. We present a
      retrospective, double-institution case series over a 5-year period, describing
      five children, aged 3 to 14 years, with tracheal injury after blunt cervical
      trauma. All patients showed emphysema with pneumomediastinum. After explorative
      bronchoscopy, all patients were successfully treated with antibiotics and/or
      supportive ventilation. In summary, minimal lesions due to blunt tracheal trauma
      could be treated conservatively in children. Since the external signs of tracheal
      injury are not indicative of the extent of the trauma, a high index of suspicion
      is warranted in these patients.

PMID- 17028882
TI  - Strategies to screen for adrenal suppression in children with asthma should take
      account of compliance with inhaled corticosteroids.

PMID- 17028883
TI  - Use of psychotropic medications in Italian children and adolescents.
AB  - INTRODUCTION: The evidence of psychotropic drug safety and efficacy in the
      pediatric population is scant and widely debated. Yet, the prescription
      prevalence and incidence are increasing. A drug utilization study, based on a
      multiregional prescription database was therefore carried out in a sample of
      1,484,770 Italian children and adolescents younger than 18 years during the year
      2004. Furthermore, the trend of psychotropic prescription prevalence was
      evaluated from 1998 to 2004. During 2004, 4,316 children and adolescents received
      psychotropic drugs (2.91 per thousand youths). Antidepressants were prescribed to
      3,503 youths (2.36 per thousand), antipsychotics to 1,005 (0.68 per thousand),
      and lithium to 73 (0.05 per thousand). A total of 265 youths received drugs from
      more than one psychotropic class. The prevalence rate of psychotropic drug
      prescriptions increased with increasing age, with a statistically significant
      trend ([Formula: see text]; p<0.0001), and it increased in the period 1998-2004
      with a statistically significant trend ([Formula: see text]; p<0.0001), reaching
      its highest value in 2002 (3.08 per thousand). The trend for antidepressants was
      similar ([Formula: see text]; p<0.0001), while the prevalence of antipsychotics
      did not increase. CONCLUSION: Even though the prevalence of psychotropic drug
      prescriptions in Italian children is lower than that reported in other countries
      (e.g. United States, Canada, Netherlands, UK), the increase in antidepressant
      prescriptions raises some concerns. Data concerning safety and efficacy of these
      antidepressants in pediatrics are still limited and further studies are needed to
      guarantee evidence based therapeutic approaches in children, adolescents and
      their families.

PMID- 17028884
TI  - Extending the mirror neuron system model, I. Audible actions and invisible
      grasps.
AB  - The paper introduces mirror neuron system II (MNS2), a new version of the MNS
      model (Oztop and Arbib in Biol Cybern 87 (2):116-140, 2002) of action recognition
      learning by mirror neurons of the macaque brain. The new model uses a recurrent
      architecture that is biologically more plausible than that of the original model.
      Moreover, MNS2 extends the capacity of the model to address data on audio-visual
      mirror neurons and on the response of mirror neurons when the target object was
      recently visible but is currently hidden.

PMID- 17028885
TI  - Do geomagnetic storms change the behaviour of the stingless bee guirucu
      (Schwarziana quadripunctata)?
AB  - Six behavioural experiments were carried out to investigate the magnetic field
      effects on the nest-exiting flight directions of the honeybee Schwarziana
      quadripunctata (Meliponini). No significant differences resulted during six
      experiment days under varying geomagnetic field and the applied static
      inhomogeneous field (about ten times the geomagnetic field) conditions. A
      surprising statistically significant response was obtained on a unique magnetic
      storm day. The magnetic nanoparticles in these bees, revealed by ferromagnetic
      resonance, could be involved in the observed effect of the geomagnetic storm.

PMID- 17028887
TI  - Adaptive-filtering of trisomy 21: risk of Down syndrome depends on family size
      and age of previous child.
AB  - The neonatal incidence rate of Down syndrome (DS) is well-known to accelerate
      strongly with maternal age. This non-linearity renders mere accumulation of
      defects at recombination during prolonged first meiotic prophase implausible as
      an explanation for DS rate increase with maternal age, but might be anticipated
      from chromosomal drive (CD) for trisomy 21. Alternatively, as there is selection
      against genetically disadvantaged embryos, the screening system that eliminates
      embryos with trisomy 21 might decay with maternal age. In this paper, we provide
      the first evidence for relaxed filtering stringency (RFS) to represent an
      adaptive maternal response that could explain accelerating DS rates with maternal
      age. Using historical data, we show that the proportion of aberrant live births
      decrease with increased family size in older mothers, that inter-birth intervals
      are longer before affected neonates than before normal ones, and that primiparae
      exhibit elevated levels of DS incidence at higher age. These findings are
      predicted by adaptive RFS but cannot be explained by the currently available
      alternative non-adaptive hypotheses, including CD. The identification of the
      relaxation control mechanism and therapeutic restoration of a stringent screen
      may have considerable medical implications.

PMID- 17028886
TI  - Women infected with parasite Toxoplasma have more sons.
AB  - The boy-to-girl ratio at birth (secondary sex ratio) is around 0.51 in most
      populations. The sex ratio varies between societies and may be influenced by many
      factors, such as stress and immunosuppression, age, primiparity, the sex of the
      preceding siblings and the socioeconomic status of the parents. As parasite
      infection affects many immunological and physiological parameters of the host, we
      analyzed the effect of latent toxoplasmosis on sex ratios in humans. Clinical
      records of 1,803 infants born from 1996 to 2004 contained information regarding
      the mother's age, concentration of anti-Toxoplasma antibodies, previous
      deliveries and abortions and the sex of the newborn. The results of our
      retrospective cohort study suggest that the presence of one of the most common
      parasites (with a worldwide prevalence from 20 to 80%), Toxoplasma gondii, can
      influence the secondary sex ratio in humans. Depending on the antibody
      concentration, the probability of the birth of a boy can increase up to a value
      of 0.72, C.I.95 = (0.636, 0.805), which means that for every 260 boys born, 100
      girls are born to women with the highest concentration of anti-Toxoplasma
      antibodies. The toxoplasmosis associated with immunosuppression or
      immunomodulation might be responsible for the enhanced survival of male embryos.
      In light of the high prevalence of latent toxoplasmosis in most countries, the
      impact of toxoplasmosis on the human population might be considerable.

PMID- 17028888
TI  - First evidence of poisonous shrews with an envenomation apparatus.
AB  - Herein, we report evidence of an envenomation apparatus (EA) in two different
      species of extinct "giant" shrews, Beremendia and an indeterminate soricine
      (Mammalia, Eulipotyphla, Soricidae), documented by very well preserved fossil
      specimens recovered from two Early Pleistocene cave deposits of the Sierra de
      Atapuerca in Burgos, Spain. The two soricine taxa from Atapuerca have evolved
      specialized teeth as EAs, which differ from those of recently reported mammals of
      the Paleocene age, being more similar to the ones described in the modern
      Solenodon. This discovery reveals the first instance of shrews possessing what
      appears to be an EA, an evolutionary adaptation that, in these species, was
      probably related to an increase in body mass and hunting of a larger-sized prey.
      The Atapuerca specimens would have a highly specialized EA, one of the very few
      reported for an extinct or living mammal of any time. In addition to the presence
      of a gutter-like groove along the medial side of the crown of the lower incisors,
      these two species also present stout jaws and a modified mandibular symphysis
      with a conspicuous cavity, which in life would likely contain large amounts of
      connective tissue. The strong mandible architecture of these large shrews would
      be, in this way, reinforced by a more immovable symphysis, increasing the bite
      force exerted over a potential prey. This adaptation, together with the grooved
      incisors, would ensure a rapid and efficient transmission of the poisonous saliva
      to paralyze relatively large-sized prey.

PMID- 17028889
TI  - Concentrations of cortisol, testosterone and glycosylated haemoglobin (HbA1c)
      among construction workers with 12-h workdays and extended workweeks.
AB  - OBJECTIVES: Working on large scale construction sites have been shown to have
      severe health consequences in terms of increased risk of hospitalization and
      disability retirement compared to construction work in general. The aim of the
      present study was to investigate whether large scale construction work involving
      12-h workdays and extended workweeks leads to insufficient recovery measured as
      increased catabolic and decreased anabolic metabolism. METHODS: The study group
      comprised 40 male construction workers of which 21 had 12-h workdays and extended
      workweeks (56 h/workweek). The comparison group consisted of 19 male construction
      workers, who worked regular hours (37 h/week, weekends off). Measurements of
      concentrations of cortisol in saliva and free testosterone and glycosylated
      haemoglobin (HbA(1c)) in blood were made in a repeated measures design during 2
      workweeks for both groups supplemented with 1 week off for construction workers
      with extended workweeks. RESULTS: The diurnal profile of concentrations of
      salivary cortisol for construction workers with extended workweeks differed from
      the diurnal profile of salivary cortisol for those with regular work schedules (P
      < 0.001). The construction workers with extended workweeks tended to have 15%
      [95% CI -3%; 37%] higher concentrations of free testosterone in serum compared to
      construction workers with regular work schedules (P = 0.09). There were no
      differences between the two groups with respect to concentrations of HbA(1c).
      There was no increasing trend in concentrations of cortisol or decreasing trend
      in concentrations of testosterone during the extended workweek. The diurnal
      profile for concentrations of cortisol differed between workdays and days off for
      construction workers with extended workweeks (P = 0.003). CONCLUSION: In
      conclusion, we observed no indications of insufficient recovery in terms of
      increased catabolic or decreased anabolic metabolism in construction workers with
      12-h workdays and extended workweeks compared to construction workers with
      regular work schedules.

PMID- 17028890
TI  - Clinical validity of the Japanese version of the Functional Assessment of Cancer
      Therapy-Anemia Scale.
AB  - GOALS OF WORK: The purpose of this study was to reveal the clinical validity of
      the Japanese version of the Functional Assessment of Cancer Therapy-Anemia scale
      (FACT-An) in relation to hemoglobin level. We also analyzed patients' scores for
      the related FACT-General scale (FACT-G), the FACT Anemia subscale, and the FACT
      Trial Outcome Index-Anemia scale (FACT TOI-An) to determine which was the most
      sensitive to anemia measurements. MATERIALS AND METHODS: Throughout Japan, we
      recruited 227 patients (mean+/-SD, 59+/-12.1 years old) diagnosed with a variety
      of cancers. We correlated the severity of anemia, as measured by hemoglobin
      levels, to scores on the FACT-An and on the other scales at baseline and at 3
      months. MAIN RESULTS: The questionnaire completion rate was more than 98% at both
      time points. The FACT-An had high internal consistency (Cronbach's alpha
      coefficient >0.8). FACT-An scores were significantly and positively correlated
      with hemoglobin levels both at baseline (r=0.24; 95% CI=0.12 to 0.36; n=225) and
      at 3 months (r=0.24; 95% CI=0.10 to 0.36; n=204). FACT-G, FACT Anemia subscale,
      and FACT TOI-An scores also successfully discriminated between patients with
      lower (Hb <11.0 g/dl) and higher (Hb > or =11.0 g/dl) hemoglobin levels.
      Moreover, the changes of these FACT scores over 3-months could discriminate
      changes in hemoglobin level. CONCLUSION: The Japanese version of the FACT-An has
      higher clinical validity and can be used to appropriately assess health-related
      quality of life among Japanese cancer patients with anemia.

PMID- 17028891
TI  - Temporal order judgment in dyslexia.
AB  - Hari et al. (Brain 174:1373-1380, 2001) demonstrated that dyslexics showed a
      sluggish attention capture in both visual hemifields. Additionally, they
      indicated a left-right asymmetry in the perception of temporal order of two
      visual stimuli (they performed worse than controls only if the stimulus in the
      left hemifield preceded that in right hemifield). They suggested that a left
      sided minineglect is associated with dyslexia. We hypothesized that if a kind of
      neglect syndrome is responsible for the asymmetry they found, dyslexics should
      not only show a left-right asymmetry in temporal order judgment of two laterally
      presented stimuli but also perform equally well as controls when the stimuli are
      vertically aligned. Our results indicated that in both tasks dyslexics performed
      generally worse than normal readers. The results suggest that dyslexics suffer
      from a more general problem of order discrimination.

PMID- 17028892
TI  - Nucleus accumbens subregions: hodological and immunohistochemical study in the
      domestic chick (Gallus domesticus).
AB  - The nucleus accumbens was identified in avian species some time ago. However, the
      precise localization and extent of this nucleus is still a matter of controversy.
      We have used immunolabeling against calbindin, neuropeptide Y, and DARPP-32
      (dopamine- and adenosine-related phosphoprotein, 32 kDa) for the selective
      marking of putative accumbens subdivisions and have followed the anterograde
      transport of biotinylated dextran amine injected to the nucleus tractus solitarii
      region of 7-day-old domestic chicks. The nucleus accumbens extending between
      rostrocaudal atlas coordinates A 10.6 and A 8.8 can be subdivided into the core
      and shell, the core corresponding to the ventromedial and juxtaventricular medial
      striatum laterodorsal to the bed nucleus of stria terminalis, and the shell
      representing an arched region situated ventrally and ventrolaterally to the core.
      Immunoreactivity to both calbindin and neuropeptide Y is more intense in the
      shell than in the core division. DARPP-32 immunolabeling does not differ in the
      two divisions but is markedly weaker in the bed nucleus of stria terminalis,
      enabling the separation of this nucleus from the surrounding accumbens
      subdivisions. Fibers from the nucleus solitarius predominantly terminate in the
      shell division, similar to the situation described in mammals. Whereas the
      suggested core lies entirely within the boundary of the medial striatum, the
      shell seems partially to overlap the ventral pallidum. We have been unable to
      subdivide the remaining part of accumbens lying rostral to A 10.6 into a putative
      shell and core by the methods employed in the present study. This region probably
      corresponds to the rostral pole of the nucleus accumbens.

PMID- 17028893
TI  - Modulation of cell proliferation during palatogenesis by the interplay between
      Tbx3 and Bmp4.
AB  - During secondary palate development, two shelves are elevated to a horizontal
      position above the tongue through a process involving many cellular mechanisms,
      including proliferation. In particular, the expression patterns of Tbx3 and Bmp4,
      which are colocalized at embryonic day 13.5 (E13.5) and have unique expression
      patterns in specific regions at E14.5, have been investigated in early mouse
      palatogenesis. Tbx3 expression is reported to be associated with Bmp4 signaling
      during the process of organogenesis in other areas, such as limb development.
      However, the function of Tbx3 and the relationship between Tbx3 and Bmp4 in
      palate development have not been determined. We have examined the gene expression
      pattern and cell proliferation in order to understand the mutual interactions and
      function of Tbx3 and Bmp4. An electroporation method was used to investigate the
      altered pattern of these genes after their over-expression in organ cultures.
      NOGGIN protein-soaked beads were also implanted into the cultured palate to
      determine the function of Bmp4 in palatogenesis. After electroporation and NOGGIN
      bead implantation, the number of PCNA-positive cells was counted. The results
      showed that Tbx3 and Bmp4 strongly up- and down-regulated each other in order to
      control the proliferation of the palatal shelf. Thus, Tbx3 expression is induced
      by Bmp4 in the mesenchyme of the anterior palatal shelves, whereas mesenchymal
      expression of Tbx3 down-regulates Bmp4 expression in the mesenchyme of the
      palate. The harmonization between Tbx3 and Bmp4 therefore controls cell
      proliferation to regulate secondary palate development.

PMID- 17028894
TI  - Molecular, cellular and histological changes in skin from a larval to an adult
      phenotype during bony fish metamorphosis.
AB  - Developmental models for skin exist in terrestrial and amphibious vertebrates but
      there is a lack of information in aquatic vertebrates. We have analysed skin
      epidermal development of a bony fish (teleost), the most successful group of
      extant vertebrates. A specific epidermal type I keratin cDNA (hhKer1), which may
      be a bony-fish-specific adaptation associated with the divergence of skin
      development (scale formation) compared with other vertebrates, has been cloned
      and characterized. The expression of hhKer1 and collagen 1alpha1 in skin taken
      together with the presence or absence of keratin bundle-like structures have made
      it possible to distinguish between larval and adult epidermal cells during skin
      development. The use of a flatfish with a well-defined larval to juvenile
      transition as a model of skin development has revealed that epidermal larval
      basal cells differentiate directly to epidermal adult basal cells at the climax
      of metamorphosis. Moreover, hhKer1 expression is downregulated at the climax of
      metamorphosis and is inversely correlated with increasing thyroxin levels. We
      suggest that, whereas early mechanisms of skin development between aquatic and
      terrestrial vertebrates are conserved, later mechanisms diverge.

PMID- 17028895
TI  - The clipped intestinal non-perforating anastomosis of small bowel: a new
      technique.
AB  - In contrast to adult surgery, the neonatal small intestine confronts the surgeon,
      depending on the age of the patient, with variable diameters of the intestine.
      Therefore, anastomoses are usually performed by hand with interrupted sutures. In
      the presented study, a new technique is demonstrated. An anastomosis in the
      distal ileum of Sprague Dawley rats was performed with a single clamp applicator
      (Anastoclip). Small bowel anastomoses were performed in 32 rats. The clipped
      bowel anastomosis was evaluated concerning stenosis, leakage, and adhesions in
      comparison to the sutured anastomosis. Tension test and X-ray examination were
      performed to measure the stability. The rats were sacrificed at day 3 or 14 after
      laparotomy. The clipped anastomosis is feasible, and faster to perform than the
      conventional hand-sutured anastomosis (Operation time: control group: 18.5 min
      versus clipped group 4 min; p > 0.05). Furthermore, there were differences in the
      mechanical stability, with higher tension forces needed for rupturing the clipped
      anastomosis. There were fewer stenoses (16.5 mm stenotic diameter in the control
      group versus 20.6 mm in the clipped group) and fewer adhesions in the group of
      the clipped anastomosis. Histological examinations were performed and did not
      show significant differences between the two groups. In the animal model
      presented, the clipped, intestinal, non-perforating anastomosis (CINPA) shows
      advantages compared to the common hand-sutured anastomosis.

PMID- 17028897
TI  - Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical
      outcomes in HLA-matched sibling allogeneic hematopoietic stem cell
      transplantation.
AB  - To evaluate whether the C677T and A1298C polymorphisms of 5,10
      methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of
      methotrexate (MTX) used in allogeneic stem cell transplantation, we performed
      association analysis between these genetic polymorphisms and the clinical
      outcomes of patients treated using human leukocyte antigen-matched sibling stem
      cell transplantation. Patients (n=72) with hematological malignancy or aplastic
      anemia were given a short course of MTX as a graft-versus-host disease
      prophylaxis. Patients with the 677TT genotype showed higher total bilirubin
      levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07)
      and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6
      vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients
      with the 677TT genotype than for patients with other genotypes (677TT, 59 days;
      677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T
      polymorphism on treatment-related mortality (TRM) were also analyzed. One-year
      cumulative TRMs for patients with the TT genotype and the other genotypes were 66
      and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56%
      (p=0.11). No association was observed between the A1298C polymorphism and
      clinical outcome for any of the different genotypes. Therefore, patients at high
      risk of developing hepatic toxicity and with a poor likelihood of survival could
      be selected by genotyping MTHFR C677T before allogeneic stem cell
      transplantation.

PMID- 17028896
TI  - Hematological malignancies in chronic inflammatory bowel diseases: report of five
      cases and review of the literature.
AB  - Several forms of primary and secondary hematological malignancies were rarely
      observed during the clinical course of inflammatory bowel diseases (IBD).
      Patients needing a prolonged treatment with immunosuppressants, such as
      azathioprine or methotrexate, with familiarity and genetic predisposition seem to
      be at a higher risk of leukemia. On the other hand, asthenia, thickness, and
      fever may be the symptoms of the onset of each kind of hematological malignancy.
      The finding of anemia, alteration of leukocyte count and large undetermined cells
      may suggest increased probability of abnormal proliferation of a single white
      blood cell line. In this report, the occurrence of hematological malignancies is
      described in five patients affected by IBD (three with ulcerative colitis and two
      with Crohn's disease) attending our Gastroenterology Unit.

PMID- 17028898
TI  - Contrasting insulin dose-dependent defects in activation of atypical protein
      kinase C and protein kinase B/Akt in muscles of obese diabetic humans.
AB  - AIMS/HYPOTHESIS: Insulin-stimulated glucose transport in muscle is impaired in
      obesity and type 2 diabetes, but alterations in levels of relevant signalling
      factors, i.e. atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt),
      are still uncertain. Clamp studies using maximal insulin concentrations have
      revealed defects in activation of aPKC, but not PKB, in both obese non-diabetic
      and obese diabetic subjects. In contrast, clamp studies using submaximal insulin
      concentrations revealed defects in PKB activation/phosphorylation in obese non
      diabetic and diabetic subjects, but changes in aPKC were not reported. The aim of
      this study was to test the hypothesis that dose-related effects of insulin may
      account for the reported differences in insulin signalling to PKB in diabetic
      muscle. SUBJECTS AND METHODS: We compared enzymatic activation of aPKC and PKB,
      and PKB phosphorylation (threonine-308 and serine-473) during hyperinsulinaemic
      euglycaemic clamp studies using both submaximal (400-500 pmol/l) and maximal
      (1400 pmol/l) insulin levels in non-diabetic control and obese diabetic subjects.
      RESULTS: In lean control subjects, the submaximal insulin concentration increased
      aPKC activity and glucose disposal to approximately 50% of the maximal level and
      PKBbeta activity to 25% of the maximal level, but PKBalpha activity was not
      increased. In these subjects, phosphorylation of PKBalpha and PKBbeta was
      increased to near-maximal levels at submaximal insulin concentrations. In obese
      diabetic subjects, whereas aPKC activation was defective at submaximal and
      maximal insulin concentrations, PKBbeta activation and the phosphorylation of
      PKBbeta and PKBalpha were defective at submaximal, but not maximal, insulin
      concentrations. CONCLUSIONS/INTERPRETATIONS: Defective PKBbeta
      activation/phosphorylation, seen on submaximal insulin stimulation in diabetic
      muscle, may largely reflect impaired activation of insulin signalling factors
      present in concentrations greater than those needed for full PKB
      activation/phosphorylation. Defective aPKC activation, seen at all insulin
      levels, appears to reflect, at least partly, an impaired action of distal factors
      needed for aPKC activation, or poor aPKC responsiveness.

PMID- 17028899
TI  - Increased intestinal permeability precedes clinical onset of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Recent observations have shown subclinical intestinal
      abnormalities in human type 1 diabetes. Whether these are related to the
      pathogenetic process or secondary to the diabetes remains to be clarified. The
      aim of this study was to investigate this issue by examining intestinal
      permeability to sugars in subjects at different stages of type 1 diabetes:
      preclinical, new-onset and long-term established disease. METHODS: Eighty-one
      subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term
      type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose
      mannitol test, consisting of oral administration of the two sugars and
      measurement of their urinary excretion. RESULTS: All groups of subjects with
      islet autoimmunity showed an increase in intestinal permeability (p < or = 0.009
      vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but
      a similar permeability to the monosaccharide mannitol (NS vs controls),
      indicative of an integral surface mucosa; consequently there was an increase in
      the lactulose:mannitol excretion ratio (p < or = 0.025 vs controls).
      CONCLUSIONS/INTERPRETATION: These findings indicate the presence of a subclinical
      enteropathy associated with type 1 diabetes that is already detectable before
      clinical onset of the disease, and suggest that the small intestine is an organ
      participating in the pathogenetic process of type 1 diabetes.

PMID- 17028900
TI  - Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a complex disease entity comprised of
      three distinct clinical syndromes that demonstrate indistinguishable histology.
      These syndromes are: eosinophilic granuloma, which is predominantly osseous or
      pulmonary; Hand-Schuller-Christian's disease, which involves multiple organ
      systems and, most typically, the skull base; and Letterer-Siwe's disease, the
      most severe disease manifestation, which typically involves the abdominal
      viscera. This article reviews our current understanding of Langerhans cell
      histiocytosis by discussing the history, histology, etiology, and treatment of
      the disease. It focuses on the radiographic findings and imaging modalities that
      are the most useful in disease diagnosis and management.

PMID- 17028901
TI  - Radiologic findings of the flexor pollicis longus hypoplasia.
AB  - A case of a 10-year-old boy with hypoplasia of the flexor pollicis longus and
      without other associated anomalies and trauma history is reported. Flexor
      pollicis longus tendon anomalies are rare; several types of this congenital
      anomaly have been reported in the literature. The diagnosis should be considered
      to the conditions of a patient who was unable to flex the interphalangeal joint
      of the thumb. Hypoplastic thumb or absent interphalangeal joint crease may be a
      diagnostic feature in such cases. We preoperatively present the radiological
      findings of this rare congenital anomaly. Ultrasound and magnetic resonance
      imaging (MRI) features have never been reported in the literature.

PMID- 17028902
TI  - A comparison of experimental designs for selection in breeding trials with nested
      treatment structure.
AB  - Plant breeders frequently evaluate large numbers of entries in field trials for
      selection. Generally, the tested entries are related by pedigree. The simplest
      case is a nested treatment structure, where entries fall into groups or families
      such that entries within groups are more closely related than between groups. We
      found that some plant breeders prefer to plant close relatives next to each other
      in the field. This contrasts with common experimental designs such as the alpha
      design, where entries are fully randomized. A third design option is to randomize
      in such a way that entries of the same group are separated as much as possible.
      The present paper compares these design options by simulation. Another important
      consideration is the type of model used for analysis. Most of the common
      experimental designs were optimized assuming that the model used for analysis has
      fixed treatment effects. With many entries that are related by pedigree, analysis
      based on a model with random treatment effects becomes a competitive alternative.
      In simulations, we therefore study the properties of best linear unbiased
      predictions (BLUP) of genetic effects based on a nested treatment structure under
      these design options for a range of genetic parameters. It is concluded that BLUP
      provides efficient estimates of genetic effects and that resolvable incomplete
      block designs such as the alpha-design with restricted or unrestricted
      randomization can be recommended.

PMID- 17028904
TI  - A randomized comparison between intravaginal misoprostol and prostaglandin E2 for
      labor induction.
AB  - OBJECTIVE: The aim of this randomized study was to compare the effectiveness,
      safety, and side effects of 6 h vaginal misoprostol versus vaginal prostaglandin
      E(2) (PGE(2)) for labor induction. STUDY DESIGN: Fifty microgram of misoprostol
      was given intravaginally in the misoprostol group (204 women), and 3 mg PGE(2)
      was given intravaginally in the PGE(2) group (211 women). In both groups, the
      dose was repeated every 6 h for a maximum of three doses, until active labor was
      achieved. Artificial rupture of membranes and oxytocin infusion was used during
      labor in both groups where it was indicated. RESULTS: The mean interval from the
      institution of labor induction to delivery was 11.3 +/- 8.6 h for the misoprostol
      group, and 15.7 +/- 9.3 h for PGE(2 )group (P < 0.05). In the misoprostol group,
      oxytocin was used less frequently, but there was a higher prevalence of
      tachysystole. No statistically significant differences were observed between the
      two groups as regard abnormal patterns of fetal heart rate, the mode of delivery,
      and the need for neonatal intervention. CONCLUSION: In conclusion, the
      intravaginal administration of 50 mug misoprostol at 6 h interval (maximum three
      doses) is comparable in safety, but more effective for induction of labor than 3
      mg intravaginal PGE(2).

PMID- 17028905
TI  - Evaluation of Eustachian tube function by sonotubometry: results and reliability
      of 8 kHz signals in normal subjects.
AB  - Sonotubometry allows an assessment of the Eustachian tube (ET) function under
      physiological conditions. The reliability of the application of an 8 kHz pure
      tone signal was investigated. In 40 normal subjects (80 ears) sonotubometric
      studies were performed with a custom-made device. ET opening was provoked by
      swallowing, yawning and Valsalva manoeuvre. An opening was detected in all
      patients but not in all manoeuvres. Four characteristic sonotubogram types were
      found. Most common was the spike-type (60%). The double-peak and the plateau
      shaped curves occurred in 17% each. The finding of an descendant curve was rare
      (5%). Of 623 measurements, only in 55% manouvres a positive sonotubometric result
      was found despite the fact that the patients reported an opening in all cases.
      The median opening time in dry swallowing, liquid swallowing, yawning and
      Valsalva was found to be 486, 355, 1,263 and 1,250 ms. A median sound increase of
      16.0, 13.8, 15.0 and 15.0 dB was recorded for these manoeuvres. There was a
      statistic significant difference (P < 0.02) between the increase in sound
      intensity of liquid and dry swallowing. There was also a statistic significant
      difference found for the duration of the forced manoeuvres Valsalva and yawning
      as compared to dry and liquid swallowing (P < 0.0001). The use of an 8 kHz pure
      tone signal showed a limited sensitivity for the detection of ET openings. This
      is mainly due to noise pollution, but also because of an altered positioning
      and/or dislocation of the probes and compression of the nostrils. The application
      of an 8 kHz signal is therefore not reliable enough for the use in practice.
      Further technical refinements and the use of alternative signals are necessary
      for a broader clinical application.

PMID- 17028906
TI  - Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis
      of patients with MYCN-amplified neuroblastoma.
AB  - PURPOSE: Amplification of the MYCN gene strongly correlates with advanced stage,
      rapid tumor progression and poor prognosis in neuroblastoma (NB). Several genes
      in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and
      neuroblastoma-amplified gene (NAG gene), have been found to be frequently co
      amplified with MYCN in NB. The aim of this study was to clarify the prognostic
      significance of the co-amplification or overexpression of DDX1 and NAG with MYCN.
      PROCEDURE: The gene copy numbers and mRNA expression levels of MYCN, DDX1, and
      NAG in 113 primary NBs were determined by the real-time quantitative polymerase
      chain reaction or quantitative reverse transcriptase/polymerase chain reaction
      assay. The relationships between gene co-amplification/overexpression status and
      stage, age at diagnosis, and overall survival were analyzed. RESULTS: For
      evaluating the frequency of DDX1 and NAG co-amplification, it proved appropriate
      to discriminate NBs with <40 copies of MYCN amplification from those with > or
      =40 copies of MYCN (DDX1, p = 0.00058; NAG, p = 0.0242, chi(2) for independence
      test). In patients with MYCN-amplified NB aged > or =18 months, those with tumor
      with enhanced DDX1 expression and low-NAG expression showed a significantly
      better outcome than those with low-DDX1 expression or enhanced NAG expression (p
      = 0.0245, log-rank test). None of the gene expression statuses had a significant
      relation to disease stage or survival for patients <18 months old. No
      relationship between any gene co-amplification status and disease stage, age at
      diagnosis, or overall survival was found. CONCLUSIONS: Our findings suggest that
      there may be a subset of NB in which enhanced DDX1 and low-NAG expression
      consequent to DDX1 co-amplification without NAG amplification contributes to
      susceptibility to intensive therapy. A larger study using an age cut-off of 18
      months will be required.

PMID- 17028907
TI  - Electro-encephalogram based brain-computer interface: improved performance by
      mental practice and concentration skills.
AB  - Mental imagination is the essential part of the most EEG-based communication
      systems. Thus, the quality of mental rehearsal, the degree of imagined effort,
      and mind controllability should have a major effect on the performance of electro
      encephalogram (EEG) based brain-computer interface (BCI). It is now well
      established that mental practice using motor imagery improves motor skills. The
      effects of mental practice on motor skill learning are the result of practice on
      central motor programming. According to this view, it seems logical that mental
      practice should modify the neuronal activity in the primary sensorimotor areas
      and consequently change the performance of EEG-based BCI. For developing a
      practical BCI system, recognizing the resting state with eyes opened and the
      imagined voluntary movement is important. For this purpose, the mind should be
      able to focus on a single goal for a period of time, without deviation to another
      context. In this work, we are going to examine the role of mental practice and
      concentration skills on the EEG control during imaginative hand movements. The
      results show that the mental practice and concentration can generally improve the
      classification accuracy of the EEG patterns. It is found that mental training has
      a significant effect on the classification accuracy over the primary motor cortex
      and frontal area.

PMID- 17028908
TI  - A comparison of nicotine dose estimates in smokers between filter analysis,
      salivary cotinine, and urinary excretion of nicotine metabolites.
AB  - RATIONALE: Nicotine uptake during smoking was estimated by either analyzing the
      metabolites of nicotine in various body fluids or by analyzing filters from
      smoked cigarettes. However, no comparison of the filter analysis method with body
      fluid analysis methods has been published. OBJECTIVES: Correlate nicotine uptake
      estimates between filter analysis, salivary cotinine, and urinary excretion of
      selected nicotine metabolites to determine the suitability of these methods in
      estimating nicotine absorption in smokers of filtered cigarettes. MATERIALS AND
      METHODS: A 5-day clinical study was conducted with 74 smokers who smoked 1-19 mg
      Federal Trade Commission tar cigarettes, using their own brands ad libitum.
      Filters were analyzed to estimate the daily mouth exposure of nicotine. Twenty
      four-hour urine samples were collected and analyzed for nicotine, cotinine, and
      3'-hydroxycotinine plus their glucuronide conjugates. Saliva samples were
      collected daily for cotinine analysis. RESULTS: Each method correlated
      significantly (p < 0.01) with the other two. The best correlation was between the
      mouth exposure of nicotine, as estimated by filter analysis, and urinary nicotine
      plus metabolites. Multiple regression analysis implies that saliva cotinine and
      urinary output are dependent on nicotine mouth exposure for multiple days.
      Creatinine normalization of the urinary metabolites degrades the correlation with
      mouth exposure. CONCLUSIONS: The filter analysis method was shown to correlate
      with more traditional methods of estimating nicotine uptake. However, because
      filter analysis is less complicated and intrusive, subjects can collect samples
      easily and unsupervised. This should enable improvements in study compliance and
      future study designs.

PMID- 17028909
TI  - Initial experience with Lodox Statscan imaging system for detecting injuries of
      the pelvis and appendicular skeleton.
AB  - The purpose of this study is to assess detection of pelvic and extremity injuries
      employing a rapid whole-body imaging system (Lodox Statscan). We retrospectively
      reviewed 37 consecutive cases. The study was approved by our hospital review
      board and carried out with Health Insurance Portability and Accountability Act
      (HIPAA) compliance. Anterior-posterior (AP) whole-body Lodox Statscan (LS) exams,
      obtained in 10-13 s, were reviewed by two musculoskeletal radiologists. Each
      patient's concurrent computed radiographs (CR) and computed tomographic (CT)
      studies were reviewed at a later date. There were 23 males and 14 females; ages
      ranged from 14 to 103 years (average 40 years). Sixteen patients had a total of
      73 abnormalities seen on LS, CR or CT. The LS examination identified 47
      abnormalities (64.4%) in 15 patients. Twenty-six additional abnormalities were
      detected with the other modalities (CR, CT) in 11 patients; 8 were evident on LS
      images in retrospect, with the remaining 18 not identified even retrospectively.
      Of these retrospectively occult injuries, only one was deemed significant to the
      acute management of the patient. The LS imaging system seems to be a useful tool
      for rapid screening of multitrauma patients.

PMID- 17028910
TI  - Utilization of thick (>3 mm) maximum intensity projection images in coronary CTA
      interpretation.

PMID- 17028911
TI  - Teleradiology by resident education.

PMID- 17028912
TI  - Effect of spatial frequency of stimulus on focal macular ERGs in monkeys :
      fmacERG dependence on the spatial-frequency.
AB  - PURPOSE: To determine the effect of the spatial frequency of a small grating
      stimulus centered on the macula on the focal macular ERGs (fmacERGs) of monkeys.
      METHODS: fmacERGs were recorded from eight eyes of four adult monkeys (Macaca
      fuscata). The spatial frequency of the stimulus was changed from 0.25 to 8
      cycles/degree. The luminance of the light bars was 10 cd/m(2), and the contrast
      was 95%. The stimulus was flashed on and off with an on duration of 100 ms and an
      off duration of 150 ms (4 Hz). The stimulus was centered on the fovea and
      subtended 12.7 degrees at the cornea. The luminance of the steady light-adapting
      background was 3.5 cd/m(2). The location of the stimulus on the retina was
      monitored throughout the recordings. The effects of the spatial frequency of the
      stimulus on the amplitudes and implicit times of the a-waves, b-waves, and
      oscillatory potentials (OPs) were determined. fmacERGs were also recorded
      following intravitreal tetrodotoxin (TTX). RESULTS: The amplitudes of the a- and
      b-waves did not change with changes in the spatial frequency of the stimulus. The
      OPs, on the other hand, responded best to the lowest spatial frequency, and the
      OPs after the first two were attenuated at intermediate and higher frequencies
      (Wilcoxon signed-rank test: P < 0.05). TTX reduced all OP wavelets in monkeys.
      CONCLUSIONS: The OPs of the photopic macular ERGs are affected by the spatial
      frequency of the stimulus and are reduced by TTX, consistent with their being
      generated by inner retinal neurons.

PMID- 17028914
TI  - Who are susceptible to pseudomembranous colitis among patients with presumed
      antibiotic-associated diarrhea?
AB  - PURPOSE: Pseudomembranous colitis is a severe form of antibiotic-associated
      diarrhea. However, there have been no reports about the factors that make
      patients with presumed antibiotic-associated diarrhea susceptible to
      pseudomembranous colitis. This study was designed to determine the clinical risk
      factors for pseudomembranous colitis among the patients with presumed antibiotic
      associated diarrhea. METHODS: This was a retrospective study of 150 consecutive
      patients admitted to our institution between January 2000 and December 2004 with
      a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent
      sigmoidoscopy or colonoscopy because of diarrhea after administration of
      antibiotics. Pseudomembranous colitis was confirmed both endoscopically and
      histologically. Various clinical parameters were compared between the
      pseudomembranous colitis group and non-pseudomembranous colitis group. RESULTS:
      The mean age of patients was 61 years, and 60 percent (90/150) was female.
      Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate
      analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than
      15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of
      antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029)
      were significant parameters for pseudomembranous colitis. On multivariate
      analysis, the important clinical risk factors were advanced age (older than aged
      70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208-6.131;
      P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1;
      95 percent confidence interval, 2.1-12.259; P < 0.0001). When both risk factors
      were present, the positive predictive value of pseudomembranous colitis was 0.86.
      CONCLUSIONS: Advanced age and long hospital stay may make patients with presumed
      antibiotic-associated diarrhea susceptible to pseudomembranous colitis.
      Therefore, pseudomembranous colitis should be first suspected in cases with
      presumed antibiotic-associated diarrhea having such risk factors.

PMID- 17028915
TI  - Evaluation of a protocol-based management of rectal cancer.
AB  - INTRODUCTION: The management of rectal cancer is multidisciplinary. We have
      devised and implemented a standardized protocol. This study was designed to
      evaluate the protocol and identify areas for improvement. METHODS: All patients
      with a diagnosis of rectal cancer were staged preoperatively. Magnetic resonance
      imaging and computed tomography were used to predict whether surgical resection
      would be complete (RO) or involved (R1/2). Data were collected on preoperative
      adjuvant therapy, surgical procedure, and subsequent pathologic stage, including
      circumferential resection margin status. RESULTS: Between January 2000 and
      October 2002, 163 patients were studied (107 male; median age, 70 (range, 60-77)
      years). One hundred and fifty seven patients underwent surgical excision for
      rectal cancer of whom 155 were discussed in the multidisciplinary meeting. One
      hundred seventeen patients (75 percent) had pelvic magnetic resonance scan and
      staging computed tomography of chest and abdomen, whereas 38 had computed
      tomography only. Seventy-seven tumors were predicted as R0 and 78 as likely R1/2.
      In the predicted RO group, 50 had surgery alone, 25 had short-course
      radiotherapy, and 2 had chemoradiotherapy. Twelve patients (15.5 percent) had
      involved circumferential resection margin on the histologic specimen. In the
      predicted R1/2 group (n = 78), 40 patients received chemoradiotherapy, 11 had
      short-course radiotherapy, and 27 had surgery alone. Thirty patients (38.4
      percent) had involved circumferential resection margin. Circumferential margin
      involvement was seen in 11 of 40 patients (27.5 percent) who received
      chemoradiotherapy, 6 of 11 patients (54.5 percent) who received short-course
      preoperative radiotherapy, and 13 of 27 patients (48.1 percent) who had surgery
      alone. CONCLUSIONS: Protocol-driven management of rectal cancer within the
      context of a multidisciplinary team has been demonstrated to work. Regular audit
      allows for modification and improvement of the protocol as newer management
      strategies evolve.

PMID- 17028916
TI  - The impact of the allee effect in dispersal and patch-occupancy age on the
      dynamics of metapopulations.
AB  - In this paper, we introduce a Levins-type metapopulation model with empty and
      occupied patches, and dispersing population. We structure the proportion of
      occupied patches according to the patch-occupancy age. We observe that patch
      occupancy age may destabilize the metapopulation, leading to persistent
      oscillations. We also allow for the dispersal rate to vary with the proportion of
      empty patches in a monotone or unimodal way. The unimodal dependence leads to
      multiple non-trivial equilibria and bistability when the reproduction number of
      the metapopulation R < 1 but greater than a lower critical value R(*). We show
      that the metapopulation will persist independently of its initial status if R >
      1.

PMID- 17028917
TI  - Non-radioactive and colorimetric quantification of monocyte adhesion to
      endothelial cells in early atherogenesis.
AB  - Monocyte adhesion to vascular endothelium is an initial step in atherogenesis. To
      quantify this, we incubated monocytes with cultured endothelial cells, and
      quantified the adhered live monocytes using a colorimetric assay. Endothelium
      activated with lipopolysaccharide attracted monocytes in a dose-dependent manner
      and the adhesion was attenuated with post-treatments with L-ascorbic acid (53%),
      alpha- (40%) and gamma-tocopherol (39%), resveratrol (39%), and Lithospermum
      erythrorhizon root extract (45%). This non-radioactive, colorimetric assay may be
      useful for screening anti-atherogenic compounds in early atherogenesis.

PMID- 17028918
TI  - Development of an oxygen-rich biosensor using enzymatic reaction.
AB  - This work reports a novel strategy for the development of an O2-rich biosensor.
      The principle is based on an enzymatic reaction between catalase and H2O2 to
      release O2, thus to increase the O2 amount in the enzyme matrix. This method
      improves the determination reliability by alleviating the O2 dependence.

PMID- 17028919
TI  - Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but
      not the MAPK, signaling pathway.
AB  - Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in
      sarcomas showed an effect on the formation of metastases, dependent on the level
      of ezrin expression. In this study, we explore the role of ezrin in Ewing's
      sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults.
      Through both immunohistochemistry and Western immunoblot studies we find
      ubiquitous, high-level expression of ezrin in Ewing's sarcoma. In contrast to the
      observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition
      of ezrin-mediated signal transduction, through the expression of a non
      phosphorylatable T567A mutant, slows primary growth of Ewing's sarcoma cells in
      vitro. This reduction in growth is a result of increased apoptosis in the mutant
      expressing cells. We further show that expression of this mutant reduces the
      ability of Ewing's sarcoma cells to form experimental metastases in vivo.
      Molecular examination reveals that the action of ezrin in Ewing's sarcoma is
      dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These
      results, therefore, demonstrate that, in Ewing's sarcoma, the biology of ezrin is
      distinct from that described in other sarcomas. This study further validates
      ezrin as a potential therapeutic target.

PMID- 17028920
TI  - Diagnostic identification of malignant cells in the cerebrospinal fluid by tumor
      specific qRT-PCR.
AB  - Tumor specific quantitative RT-PCRs for two neuroblastoma specific molecular
      markers, tyrosine hydroxylase (TH) and GD2 synthase, were used to unequivocally
      demonstrate the neoplastic nature of the cells present in the cerebrospinal fluid
      of a neuroblastoma patient. After radical surgery of two separate tumoral
      lesions, localized in the extradural area, the patient presented with meningitis.
      Common sites of neuroblastoma metastatization, e.g. bone and bone marrow, were
      not infiltrated by tumor cells, as assessed by standard scintigraphy,
      morphological investigation and by sensitive and specific immunocytochemical and
      molecular assays. The results presented here demonstrate the successful use of
      tumor-specific qRT-PCRs in cerebrospinal fluid to investigate questionable
      clinical cases. The technique, which compared to other detection methods (e.g.,
      immunocytochemistry) requires very few cells, yields unambiguous information once
      a suspected diagnosis has been formulated and a tumor-specific molecular marker
      is available.

PMID- 17028921
TI  - Understanding metastatic SCCHN cells from unique genotypes to phenotypes with the
      aid of an animal model and DNA microarray analysis.
AB  - Metastasis of squamous cell carcinoma of the head and neck (SCCHN) is a
      significant health-care problem worldwide. The 5-year survival rate is less than
      50% for patients with lymph node metastases. Understanding the molecular basis of
      SCCHN metastasis would facilitate the development of new therapeutic approaches
      to the disease. To identify proteins that mediate SCCHN metastasis, we
      established a SCCHN xenograft mouse model and performed in vivo selection from a
      SCCHN cell line using the model. In the fourth round of in vivo selection,
      significant incidences of metastases in lymph nodes (7/10) and lungs (6/10) were
      achieved from a derived SCCHN cell line as compared with its parental cells, 1/5
      in lymph nodes and 0/5 in lungs. Metastatic cell lines from lymph node metastases
      and parental cell lines from non-metastatic xenograft tumors were subjected to
      DNA microarray analysis using an Affymetrix gene chip HG-U133A, followed by data
      mining studies. The identified metastasis-related genes were further evaluated
      for their encoding protein products and the metastatic cells were examined by
      biological analyses. DNA microarray analysis highlighted molecular features of
      the metastatic SCCHN cells, including alteration of expression of cell-cell
      adhesion proteins, epithelial cell markers, apoptosis and cell cycle regulatory
      molecules. Further biological analyses of phenotypic alterations revealed that
      the metastatic cells gained epithelial-mesenchymal transition (EMT) features and
      were more resistant to anoikis, which are two of the important phenotypes for
      metastatic SCCHN.

PMID- 17028922
TI  - Expression of a metastatic phenotype in IFNs-primed/TNFalpha-activated B16 murine
      melanoma cells: role of JAK1/PKCdelta signal transduction factors.
AB  - In previous studies, we found that IFNgamma and TNFalpha generated by activated
      macrophages stimulate the metastatic potential in F10-M3 cells, a clone isolated
      from B16-F10 murine melanoma line. In this phenomenon, TNFalpha promoted the
      expression of a metastatic phenotype in tumor cells previously primed with
      IFNgamma. Here, we demonstrate that IFNalpha or IFNbeta may replace IFNgamma in
      priming tumor cells. We also noticed that an enhancement of the expression of
      p55TNFalpha receptor was associated with the preconditioning of tumor cells with
      IFNgamma and IFNbeta. By the use of an appropriate inhibitor, we observed that
      JAK1 signal transduction pathway was involved in the expression of a metastatic
      phenotype and of p55TNFalpha receptor shown in IFNgamma- and IFNbeta-primed
      melanoma cells stimulated with TNFalpha. Furthermore, the activity of the protein
      kinase C (PKC) was required for IFNgamma-primed melanoma cells to express a
      metastatic phenotype after stimulation with TNFalpha. In conclusion, our study
      shows that a metastatic phenotype was expressed in B16 murine melanoma cells
      stimulated with TNFalpha regardless of whether the cells were primed with
      IFNgamma IFNalpha or IFNbeta. The molecular events leading to the expression of a
      metastatic phenotype in F10-M3 melanoma cells are represented by: (a) an enhanced
      expression of p55TNFalpha receptor in IFNs-primed tumor cells dependent on JAK1
      signal transduction pathway; and (b) an intact PKC activity during TNFalpha
      stimulation.

PMID- 17028923
TI  - Soluble N-cadherin fragment promotes angiogenesis.
AB  - Endothelial cells express two dependent intercellular adhesion molecules:
      vascular endothelial (VE)-cadherin, specific for endothelial cells, and N
      cadherin, also present in neuronal, lens, skeletal and heart muscle cells,
      osteoblasts, pericytes and fibroblasts. While there exists a vast amount of
      evidence that VE-cadherin promotes angiogenesis, the role of N-cadherin still
      remains to be elucidated. We found that a soluble 90-kDa fragment N-cadherin
      promotes angiogenesis in the rabbit cornea assay and in the chorioallantoic assay
      when cleaved enzymatically from the extracellular domain of N-cadherin. Soluble N
      cadherin stimulates migration of endothelial cells in the wound healing assay and
      stimulates phosphorylation of extracellular regulated kinase. In vitro
      experiments with PD173074 and knock-down of N-cadherin and fibroblast growth
      factor (FGF)-receptor, showed that the pro-angiogenic effect of soluble N
      cadherin is N-cadherin- and FGF-receptor-dependent. Our results suggest that
      soluble N-cadherin stimulates migration of endothelial cells through the FGF
      receptor.

PMID- 17028924
TI  - Stem cell factor affects tumour progression markers in metastatic melanoma cells.
AB  - Stem cell factor (SCF), next to various relevant biological effects exerted on
      many cell types, is able to keep melanocyte homeostasis through its receptor c
      kit. Only a minority of metastatic melanoma cells (MMC) express c-kit receptor,
      but c-kit positive MMC move more slowly towards tumour progression and have a
      more natural tendency to undergo apoptosis. In our study c-kit positive MMC from
      human melanoma metastases and a c-kit positive human melanoma cell line-SK-MEL-28
      showed a clear-cut reduction of cytokines normally up-regulated along melanoma
      progression after SCF stimulation. SCF was also able to maintain all MMC and SK
      MEL-28 cells in a well differentiated status with an increase in organellogenesis
      and in particular of melanosomes in various degree of differentiation, but it did
      not induce apoptosis as observed in other in vitro models. The increase of
      melanosomes matched an increase of tyrosinase production. SCF did not modify the
      expression of NOS while it enhanced the expression of HLA-DR molecules on MMC
      membranes. Taken altogether these data stress the biological activity of SCF as a
      cytokine which is able to maintain MMC in a well differentiated status, and
      suggest a more in depth evaluation of possible effects of SCF on melanoma cells.

PMID- 17028925
TI  - The inhibition of lung colonization of B16-F10 melanoma cells in EFA-deficient
      animals is related to enhanced apoptosis and reduced angiogenesis.
AB  - Previous studies conducted in our laboratory showed that the reproduction of
      spontaneous and experimental metastases was reduced in host animals deprived of
      essential fatty acids (EFA). In the present study, we have explored the
      possibility whether apoptosis, proliferation, and angiogenesis might be involved
      in the antimetastatic effect of EFA deficiency. To this aim, in pulmonary
      colonies developed from B16-F10 cells in EFA-deficient animals or in animals fed
      a 5% corn oil diet, we performed an immunohistochemical analysis of bcl-2/bax
      proteins, PCNA, and VEGF and von Willebrand Factor (vWF), typical markers of
      apoptosis, proliferation, and angiogenesis, respectively. Apoptosis was also
      evaluated by detecting DNA fragments in metastatic cells. We found that the
      reduction of pulmonary colonies grown in EFA-deficient animals was associated
      with a high expression of apoptotic activity as revealed by the presence of
      apoptotic nuclei and a high immunoreactivity for bax. Cell proliferation seemed
      not to be influenced by EFA deficiency in view of the observation that PCNA was
      highly expressed in pulmonary colonies of control as well as EFA-deficient
      animals. Pulmonary colonies developed in EFA- deficient animals showed a lower
      expression of VEGF and a decreased microvessel density, indicating that a reduced
      angiogenesis contributes to the antimetastatic effects of EFA deficiency. Our
      analysis of the results invokes the possibility that a relationship between
      angiogenesis and apoptosis may account for the diminution of the development of
      experimental metastases in the lungs of EFA-deficient animals.

PMID- 17028926
TI  - Left ventricular outflow tract myxoma accompanied by dextrocardia with situs
      inversus: a case report.
AB  - Myxoma is the most frequently encountered primary tumour of the heart, comprising
      more than 50% of all benign cardiac tumours. The case presented here was
      diagnosed as having dextrocardia with situs inversus and concomitant left
      ventricular outflow tract myxoma which has been very rarely encountered,
      particularly consistent with the scarcity of reported cases.

PMID- 17028927
TI  - Comprehensive evaluation of atrial septal defects in individuals undergoing
      percutaneous repair by 64-detector row computed tomography.
AB  - Transcatheter atrial septal defect closure is becoming more commonplace as it has
      been demonstrated to be safe, efficacious and associated with low morbidity. Pre
      procedural assessment of individuals has primarily relied upon transesophageal
      echocardiography. We present four individuals who underwent both transesophageal
      echocardiography as well as cardiac multidetector computed tomography. In all
      four cases, multidetector computed tomography added incremental information above
      the transesophageal echocardiogram. Multidetector computed tomography may play an
      essential role in individuals with atrial septal defects undergoing percutaneous
      transcatheter closure.

PMID- 17028928
TI  - Multislice CT coronary angiography for the detection of burden, morphology and
      distribution of atherosclerotic plaques in the left main bifurcation.
AB  - The aim of the study was to explore the differences in plaque burden at different
      segments of the left main bifurcation and its relationship with the bifurcation
      angle using high-resolution multislice CT coronary angiography (MSCT). Patients
      were evaluated using a 40-row MSCT scanner. One observer assessed the
      localization, severity and distribution of plaques within the left main (LMCA)
      bifurcation, whereas another observer defined the angle. Fifty patients were
      included. The mean heart rate was 59.8 +/- 7.1. Seventeen (34%) patients
      presented at least wall irregularities in the LMCA and in the ostial LCx, whereas
      the ostial LAD was affected in 32 (64%) patients. More than 90% of plaques were
      located opposite to the flow divider. The median bifurcation angle was 88.5
      degrees (IQR 68.8 degrees, 101.4 degrees). Of the 18 patients with a normal
      ostial LAD, 13 (72%) had a bifurcation angle < 88.5 degrees , whereas the 63% of
      the patients with any LAD disease had an angle >or= 88.5 degrees (P = 0.018). In
      conclusion, at the left main bifurcation, atherosclerotic plaques are commonly
      located at the ostial LAD and opposite to the flow divider. The angle of the left
      main bifurcation and the presence of plaques within the bifurcation are closely
      related.

PMID- 17028929
TI  - Kawasaki disease: role of coronary CT angiography.
AB  - Invasive coronary angiography is considered to be the gold standard for diagnosis
      and follow-up of coronary artery aneurysms, thrombosis and stenosis in patients
      with Kawasaki Disease. However, the availability of multi-detector CT coronary
      angiography provides a viable alternative as a non-invasive imaging modality for
      sequential follow-up of patients with Kawasaki disease. High quality
      multidetector CT angiography images of coronary arterial anatomy can be obtained
      after adequate heart rate control using beta blockers.

PMID- 17028930
TI  - An evolutionary heterogeneity model of late-life fecundity in Drosophila.
AB  - There is now a significant body of research that establishes the deceleration of
      mortality rates in late life and their ultimate leveling off on a late-life
      plateau. Natural selection has been offered as one mechanism responsible for
      these plateaus. The force of natural selection should also exert such effects on
      female fecundity. We have already developed a model of female fecundity in late
      life that incorporates the general predictions of the evolutionary model. The
      original evolutionary model predicts a decline in fecundity from a peak in early
      life, followed by a plateau with non-zero fecundity in late life. However, in
      Drosophila there is also a well-defined decline in fecundity among dying flies,
      here called the "death spiral". This effect produces heterogeneity between dying
      and non-dying flies. Here a hybrid evolutionary heterogeneity model is developed
      to accommodate both the evolutionary plateau prediction and the death spiral. It
      is shown that this evolutionary heterogeneity model gives a much better fit to
      late-life fecundity data.

PMID- 17028931
TI  - Supplementation with a complex of active nutrients improved dermal and epidermal
      characteristics in skin equivalents generated from fibroblasts from young or aged
      donors.
AB  - Cultured skin equivalent (SE, Mimeskin) was generated by co-culturing skin
      fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan dermal
      substrate. In order to examine donor age effect, fibroblasts from 19- (young) or
      49- (aged) year-old females were used. Culture medium was supplemented with
      nutrients complex containing soy extract, tomato extract, grape seed extract,
      white tea extract, sodium ascorbate, tocopherol acetate, zinc gluconate and
      BioMarine complex. Epidermal and dermal structure and composition were examined
      after 42 and 60 days of culture. In untreated samples, SE generated from young
      fibroblasts was superior to SE from aged fibroblasts in all characteristics.
      Those include number and regularity of keratinocyte layers, number of
      keratinocytes expressing proliferation marker Ki67, content of collagen type I,
      fibrillin-1, elastin, and SE lifespan. Effects of nutritional supplementation
      were observed in SE from both young and aged fibroblasts, however, those effects
      were more pronounced in SE from aged fibroblasts. In epidermis, the treatment
      increased number of keratinocyte layers and delayed epidermal senescence. The
      number of cells expressing Ki67 was nine folds higher than those of controls, and
      was similar to that of young cell SE. In dermis, the treatment increased mRNA
      synthesis of collagen I, fibrillin-1 and elastin. In conclusion, skin cell donor
      age had major important effect on formation of reconstructed SE. Imperfections in
      epidermal and dermal structure and composition as well as life span in SE from
      aged cells can be improved by supplementation with active nutrients.

PMID- 17028932
TI  - Oxidative stress and brain aging: is zinc the link?
AB  - Zn(2+) dyshomeostasis has been strongly linked to neuronal injury in many
      neurological conditions. Toxic accumulation of intracellular free Zn(2+)
      ([Zn(2+)](i)) may result from either flux of the cation through glutamate
      receptor-associated channels, voltage-sensitive calcium channels, or Zn(2+)
      sensitive membrane transporters. Injurious [Zn(2+)](i) rises can also result from
      release of the cation from intracellular sites such as metallothioneins (MTs) and
      mitochondria. Chronic inflammation and oxidative stress are hallmarks of aging.
      Zn(2+) homeostasis is affected by oxidative stress, which is a potent trigger for
      detrimental Zn(2+) release from MTs. Interestingly, Zn(2+) itself is a strong
      inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial
      production of reactive oxygen species. In this review, we examine how Zn(2+)
      dyshomeostasis and oxidative stress might act synergistically to promote aging
      related neurodegeneration.

PMID- 17028933
TI  - Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects.
AB  - Immunosenescence features, such as thymic involution, alteration of T-cell
      repertoire, autoimmunity and accumulation of memory/effector T cells, may be the
      result, at least in part, of a zinc deficiency, which is often observed during
      ageing. Zinc, as essential trace element, affects the immune system function and
      it is an important regulator of apoptosis of immune cells. In this study we
      addressed the question whether zinc supplementation in vitro at physiological
      doses can affect spontaneous and oxidative stress-induced apoptosis in peripheral
      blood mononuclear cells from subjects of three different age groups: young (mean
      age 28 years), old (mean age 72 years) and nonagenarians. We studied different
      parameters related to apoptosis (phosphatydilserine exposure, mitochondrial
      membrane potential, caspase 3 cleavage) and we found that zinc, while decreasing
      spontaneous apoptosis, can increase oxidative stress-induced apoptosis in an age
      related fashion, being this effect more evident in nonagenarians than in old or
      young subjects. In particular, zinc can increase late apoptosis/necrosis, a
      phenomenon that could trigger unnecessary inflammation in vivo. We surmise that
      these age-associated alterations in susceptibility to apoptosis may be due to a
      different effect of zinc on T cell subsets, that are altered in very old people,
      and finally that the zinc deficiency, which is often observed in aged subjects,
      could be a compensatory mechanism to counteract the inflammatory status of the
      elderly.

PMID- 17028934
TI  - Bacterial endosymbioses in Solemya (Mollusca: Bivalvia)--model systems for
      studies of symbiont-host adaptation.
AB  - Endosymbioses between chemosynthetic bacteria and marine invertebrates are
      remarkable biological adaptations to life in sulfide-rich environments. In these
      mutualistic associations, sulfur-oxidizing chemoautotrophic bacteria living
      directly within host cells both aid in the detoxification of toxic sulfide and
      fix carbon to support the metabolic needs of the host. Though best described for
      deep-sea vents and cold seeps, these symbioses are ubiquitous in shallow-water
      reducing environments. Indeed, considerable insight into sulfur-oxidizing
      endosymbioses in general comes from detailed studies of shallow-water protobranch
      clams in the genus Solemya. This review highlights the impressive body of work
      characterizing bacterial symbiosis in Solemya species, all of which are presumed
      to harbor endosymbionts. In particular, studies of the coastal Atlantic species
      Solemya velum and its larger Pacific congener Solemya reidi are the foundation
      for our understanding of the metabolism and physiology of marine bivalve
      symbioses, which are now known to occur in five families. Solemya velum, in
      particular, is an excellent model organism for symbiosis research. This clam can
      be collected easily from coastal eelgrass beds and maintained in laboratory
      aquaria for extended periods. In addition, the genome of the S. velum symbiont is
      currently being sequenced. The integration of genomic data with additional
      experimental analyses will help reveal the molecular basis of the symbiont-host
      interaction in Solemya, thereby complementing the wide array of research programs
      aimed at better understanding the diverse relationships between bacterial and
      eukaryotic cells.

PMID- 17028935
TI  - Karyotypic relationships among the tribes of Hypostominae (Siluriformes:
      Loricariidae) with description of XO sex chromosome system in a Neotropical fish
      species.
AB  - The family Loricariidae, with about 683 species, is one the largest fish families
      in the world. The subfamily Hypostominae was recently reviewed and is now divided
      in five tribes. With the main objective of contributing to a better understanding
      of the relationships of the members of the subfamily Hypostominae, cytogenetic
      analyses were conducted in seven species (three Hypostomini, three
      Pterygoplichthini and two Ancistrini) from Brazil and Venezuela. In
      Pterygoplichthini, all species show 2n = 52 chromosomes. In Hypostomini
      Hypostomus ancistroides has 2n = 68, H. regani 2n = 72 and Hypostomus goyazensis
      2n = 72 chromosomes. In Ancistrini Ancistrus n. sp. 1 has 2n = 39/40 with a sex
      chromosome system of the type XX/X0, which is a novelty for neotropical fishes,
      and Ancistrus n. sp. 2 has 2n = 52 chromosomes. Six species have single Ag-NORs
      and two multiple Ag-NORs. The possible cytogenetic relationships among the
      species of Hypostominae are discussed.

PMID- 17028936
TI  - Direct determination of the influence of extreme temperature on transposition and
      structural mutation rates of Drosophila melanogaster mobile elements.
AB  - Two sets of mutation accumulation lines, one reared at 28 degrees C and the other
      at 24 degrees C, were compared for their transposition and rearrangement rates of
      eleven transposable element families. The changes affecting mobile elements were
      analysed by the Southern technique and in situ hybridization. No differences were
      found between treated and control lines. The role of the host genotype in
      transposition control and the significance of structural mutations in
      transposable element dynamics are discussed.

PMID- 17028937
TI  - Diversity of endogenous small non-coding RNAs in Oryza sativa.
AB  - Small non-coding RNAs play important roles in regulating cell functions by
      controlling mRNA turnover and translational repression in eukaryotic cells. Here
      we isolated 162 endogenous small RNA molecules from Oryza sativa, which ranged
      from 16 to 35 nt in length. Further analysis indicated that they represented a
      diversity of small RNA molecules, including 17 microRNAs (miRNAs), 30 tiny non
      coding RNAs (tncRNAs) and 20 repeat-associated small interfering RNAs (rasiRNAs).
      Among 17 miRNAs, 13 were novel miRNA candidates and their potential targets were
      important regulatory genes in the rice genome. We also found that a cluster of
      small RNAs, including many rasiRNAs, matched to a nuclear DNA fragment that
      evolutionarily derived from chloroplast. These results demonstrate clearly the
      existence of distinct types of small RNAs in rice and further suggest that small
      RNAs may control gene regulation through diverse mechanisms.

PMID- 17028938
TI  - Chromosomes of three freshwater stingrays (Rajiformes Potamotrygonidae) from the
      Rio Negro basin, Amazon, Brazil.
AB  - Potamotrygonidae is the representative family of South American freshwater
      elasmobranchs. It is a monophyletic group containing 20 species grouped into
      three genera. Three species belonging to two genera of this family were collected
      from the middle Negro River, Amazonas, Brazil, and studied cytogenetically:
      Paratrygon aiereba, Potamotrygon motoro and Potamotrygon orbignyi. Paratrygon
      aiereba presented 2n = 90 chromosomes and 4M+2SM+10ST+74A. Both species of
      Potamotrygon presented 2n = 66 chromosomes and differed in their chromosomal
      formulas: P. motoro had 18M+12SM+10ST+26A and P. orbignyi had 22M+10SM+8ST+26A.
      No sex heteromorphism was detected. The Fundamental Number (FN) was 106 for the
      three species. A system of multiple NORs was found in the three species, but with
      interspecific differences in terms of location and position of the active Ag-NORs
      sites. Paratrygon aiereba presented only four sites on the short arms of two
      chromosomal pairs, both in terminal regions. Potamotrygon motoro presented seven
      sites, on the long and short arms, all in terminal regions of non-homologous
      chromosomes; P. orbignyi presented eight sites on the long arms, all in terminal
      regions, of non-homologous chromosomes. The constitutive heterochromatin was in
      pericentromeric regions of all chromosomes, and no significant interspecific
      difference was found in relation to this marker.

PMID- 17028939
TI  - Genetic spatial clustering: significant implications for conservation of wild
      soybean (Glycine soja: Fabaceae).
AB  - Knowledge of spatial patterns of genetic variation within populations of wild
      relative species has significant implications with respect to sampling strategies
      for ex situ and in situ conservation. To study spatial genetic structure of wild
      soybean (Glycine soja Sieb. et Zucc.) at the fine scale, three natural
      populations in northern China were analyzed using inter-simple sequence repeat
      (ISSR) fingerprints for estimating kinship coefficients. A regression analysis of
      kinship coefficients against spatial distances revealed that individuals
      occurring close together tended to be more genetically related. The Sp statistic
      further indicated a comparable spatial pattern among the three wild soybean
      populations with similar Sp values (mean = 0.0734, varied from 0.0645 to 0.0943)
      detected across the three populations. Genetic patches were on average ca. 20 m
      in size, and the effective neighborhood sizes varied between 10 and 15 m. The
      spatial genetic structure evident in the wild soybean populations may be
      attributed to the restricted seed dispersal and predominant inbreeding mating
      system of this species. The detection of family structure in the populations of
      wild soybean has a significant implication for the effective conservation of the
      important genetic resources.

PMID- 17028940
TI  - Spatial variation in colour morph, spotting and allozyme frequencies in the candy
      stripe spider, Enoplognatha ovata (Theridiidae) on two Swedish archipelagos.
AB  - The selective significance, if any, of many invertebrate visible polymorphisms is
      still not fully understood. Here we examine colour- and black spotting-morph
      frequencies in the spider Enoplognatha ovata in populations on two Swedish
      archipelagos with respect to different spatial scales and, in one archipelago,
      against the background of variation at four putative neutral allozyme marker
      loci. Every population studied was polymorphic for colour and 28 out of 30
      contained all three colour morphs--lineata, redimita and ovata. We found no
      evidence for a breakdown in the traditional colour morph designation previously
      suggested for other northern European populations of this species. For colour
      there is no significant heterogeneity at spatial scales greater than between
      local populations within islands. Black spotting frequencies show a similar lack
      of pattern over larger spatial scales except that there are significant
      differences between the Stockholm and Goteborg archipelagos. Measures of
      population differentiation (theta) within the Stockholm islands for the two
      visible systems show them to be significantly more differentiated than the
      neutral markers, suggesting local selection acting on them in a population
      specific manner. On the basis of previous observations and the distribution of
      spotting phenotypes on a European scale, it is argued that thermal selection
      might operate on black spotting during the juvenile stages favouring more spots
      in continental climates. It is not clear what selective forces act on colour.

PMID- 17028941
TI  - Mapping of SMV resistance gene Rsc-7 by SSR markers in soybean.
AB  - Soybean mosaic virus (SMV) is one of the most prevalent pathogens that limit
      soybean production. In this study, segregation ratios of resistant plants to
      susceptible plants in P1, P2, F1, F2 populations of Kefeng No. 1 (P1) x Nannong
      1138-2 (P2) and derived RIL populations, were used to study the inheritance of
      resistance to the SMV strain SC-7. Populations Kefeng No. 1 and F1 were found to
      be completely resistant to this SMV strain while Nannong 1138-2 was susceptible
      to it. The F2 and RIL populations segregated to fit a ratio of 3:1 and 1:1for
      resistant plants to susceptible ones, respectively. These results indicated that
      a single dominant gene, designated as Rsc-7, controlled resistance to the SMV
      strain SC-7 in Kefeng No.1. SSR markers were used to analyze the RIL population
      and MAPMAKER/EXP 3.0b was employed to establish linkage between markers and this
      resistance gene. Combining the data of SSRs and resistance identification, a
      soybean genetic map was constructed. This map, covering 2625.9 cM of the genome,
      converged into 24 linkage groups, consisted of 221 SSR markers and the resistance
      gene Rsc-7. The Rsc-7 gene was mapped to the molecular linkage group G8-D1b+W.
      SSR markers Satt266, Satt634, Satt558, Satt157, and Satt698 were found linked to
      Rsc-7 with distances of 43.7, 18.1, 26.6, 36.4 and 37.9 cM, respectively.

PMID- 17028942
TI  - Altitudinal patterns for longevity, fecundity and senescence in Drosophila
      buzzatii.
AB  - We tested for variation in longevity, senescence rate and early fecundity of
      Drosophila buzzatii along an elevational transect in Argentina, using laboratory
      reared flies in laboratory tests performed to avoid extrinsic mortality. At 25
      degrees C, females from lowland populations lived longer and had a lower
      demographic rate of senescence than females from highland populations. Minimal
      instead of maximal temperature at the sites of origin of population best
      predicted this cline. A very different pattern was found at higher test
      temperature. At 29.5 degrees C, longevity of males increased with altitude of
      origin of population. No clinal trend was apparent for longevity of females at
      29.5 degrees C. There was evidence for a trade-off between early fecundity and
      longevity at non-stressful temperature (25 degrees C) along the altitudinal
      gradient. This trait association is consistent with evolutionary theories of
      aging. Population-by-temperature and sex-by-temperature interactions indicate
      that senescence patterns are expressed in environment specific ways.

PMID- 17028943
TI  - Accelerated molecular evolution in Microtus (Rodentia) as assessed via complete
      mitochondrial genome sequences.
AB  - Microtus is one of the most taxonomically diverse mammalian genera, including
      over 60 extant species. These rodents have evolved rapidly, as the genus
      originated less than 2 million years ago. If these numbers are taken at face
      value, then an average of 30 microtine speciation events have occurred every
      million years. One explanation for the rapid rate of cladogenesis in Microtus
      could be the karyotypic differentiation exhibited across the genus: diploid
      numbers range from 17 to 64. Despite the striking chromosomal variability within
      Microtus, phenotypic variation is unremarkable. To determine whether nucleotide
      substitution rates are also elevated in voles, we sequenced the entire
      mitochondrial DNA (mtDNA) genome of the Eurasian sibling vole (Microtus
      rossiaemeridionalis). We compared this genome to another previously sequenced
      vole mtDNA genome (Microtus kikuchii) and performed pairwise sequence comparisons
      with the mtDNA genomes of ten additional mammalian genera. We found that
      microtine mtDNA genomes are evolving more rapidly than any other mammalian
      lineage we sampled, as gauged by the rate of nucleotide substitution across the
      entire mtDNA genome as well as at each individual protein-coding gene.
      Additionally, we compared substitution rates within the cytochrome b gene to
      seven other rodent genera and found that Microtus mtDNA is evolving fastest. The
      root cause of accelerated evolution in Microtus remains uncertain, but merits
      further investigation.

PMID- 17028944
TI  - Sexual dimorphism of body size and sternopleural bristle number: a comparison of
      geographic populations of an invasive cosmopolitan drosophilid.
AB  - Zaprionus indianus is a cosmopolitan drosophilid, of Afrotropical origin, which
      has recently colonized South America. The sexual dimorphism (SD) of body size is
      low, males being almost as big as females. We investigated 10 natural
      populations, 5 from America and 5 from Africa, using the isofemale line
      technique. Three traits were measured on each fly: wing and thorax length and
      sternopleural bristle number. Two indices of SD were compared, and found to be
      highly correlated (r > 0.99). For the sake of simplicity, only the female/male
      (F/M) ratio was further considered. A significant genetic variability of SD was
      found in all cases, although with a low heritability (intra-class correlation of
      0.13), about half the value found for the traits themselves. For size SD, we did
      not find any variation among continents or any latitudinal trend, and average
      values were 1.02 for wing length and 1.01 for thorax length. Bristle number SD
      was much greater (1.07). Among mass laboratory strains, SD was genetically much
      more variable than in recently collected populations, a likely consequence of
      laboratory drift. Altogether, SD, although genetically variable and prone to
      laboratory drift, is independent of size variations and presumably submitted to a
      stabilizing selection in nature.

PMID- 17028945
TI  - Non-concerted evolution of the RET76 satellite DNA family in Reticulitermes taxa
      (Insecta, Isoptera).
AB  - The evolutionary dynamics of satellite DNA is most often studied in canonical
      mating systems, where bisexuality and panmixis are the rule. In eusocial
      termites, the limited number of reproducers starting a new colony and the
      maintenance of the colony through few neotenics act as bottle-necks both in space
      and time. No data on repetitive DNA are available for Isoptera and for their
      peculiar reproductive strategy. Here we present the first satellite DNA family
      isolated in European Reticulitermes. RET76 is a G+C rich satellite embodying two
      sub-families with a 76 bp monomer. RET76 sequences are highly variable (sequence
      homology is lower than 80% within sub-families and lower than 68% in the entire
      family) and this variability is equally distributed among the eight analysed
      taxa, thus depicting a pattern of non-concerted evolution. The absence of variant
      fixation--together with the strict monomer length conservation--may be explained
      at the molecular level as due to functional constraints acting on these
      sequences, and/or at the organismic level by considering the involvement of
      eusociality in preventing or greatly reducing variant fixation, somehow mimicking
      an unisexual strategy.

PMID- 17028946
TI  - Box-Cox transformation for QTL mapping.
AB  - The maximum likelihood method of QTL mapping assumes that the phenotypic values
      of a quantitative trait follow a normal distribution. If the assumption is
      violated, some forms of transformation should be taken to make the assumption
      approximately true. The Box-Cox transformation is a general transformation method
      which can be applied to many different types of data. The flexibility of the Box
      Cox transformation is due to a variable, called transformation factor, appearing
      in the Box-Cox formula. We developed a maximum likelihood method that treats the
      transformation factor as an unknown parameter, which is estimated from the data
      simultaneously along with the QTL parameters. The method makes an objective
      choice of data transformation and thus can be applied to QTL analysis for many
      different types of data. Simulation studies show that (1) Box-Cox transformation
      can substantially increase the power of QTL detection; (2) Box-Cox transformation
      can replace some specialized transformation methods that are commonly used in QTL
      mapping; and (3) applying the Box-Cox transformation to data already normally
      distributed does not harm the result.

PMID- 17028947
TI  - Origin and evolution of the Amyrel gene in the alpha-amylase multigene family of
      Diptera.
AB  - Alpha-amylase genes often form multigene families in living organisms. In
      Diptera, a remote paralog, Amyrel, had been discovered in Drosophila, where this
      gene is currently used as a population and phylogenetic marker. The putative
      encoded protein has about 40% divergence with the classical amylases. We have
      searched the presence of the paralog in other families of Diptera to track its
      origin and understand its evolution. Amyrel was detected in a number of families
      of Muscomorpha (Brachycera-Cyclorrapha), suggesting an origin much older than
      previously thought. It has not been found elsewhere to date, and it is absent
      from the Anopheles gambiae genome. The intron-exon structures of the genes found
      so far suggest that the ancestral gene (before the duplication which gave rise to
      Amyrel) had two introns, and that subsequent, repeated and independent loss of
      one or both introns occurred in some Muscomorpha families. It seems that the
      Amyrel protein has experienced specific amino acid substitutions in regions
      generally well conserved in amylases, raising the possibility of peculiar,
      functional adaptations of this protein.

PMID- 17028948
TI  - Constitutive heterochromatin, 5S and 18S rDNA genes in Apareiodon sp.
      (Characiformes, Parodontidae) with a ZZ/ZW sex chromosome system.
AB  - Karyotype, sex chromosome system and cytogenetics characteristics of an
      unidentified species of the genus Apareiodon originating from Piquiri River
      (Parana State, Brazil) were investigated using differential staining techniques
      (C-banding and Ag-staining) and fluorescent in situ hybridization (FISH) with 5S
      and 18S rDNA probes. The diploid chromosome number was 2n = 54 with 25 pairs of
      meta- (m) to submetacentric (sm) and 2 pairs of subtelocentric (st) chromosomes.
      The major ribosomal rDNA sites as revealed by Ag-staining and FISH with 18S rDNA
      probe were found in distal region of longer arm of st chromosome pair 26, while
      minor 5S sites were observed in the interstitial sites on chromosome pairs 2
      (smaller cluster) and 7 (larger one). The C-positive heterochromatin had
      pericentromeric and telomeric distribution. The heteromorphic sex chromosome
      system consisted of male ZZ (pair 21) and female middle-sized m/st Z/W
      chromosomes. The pericentric inversion of heterochromatinized short arm of
      ancestral Z followed by multiplication of heterochromatin segments is
      hypothesized for origin of W chromosome. The observed karyotype and chromosomal
      markers corresponded to those found in other species of the genus.

PMID- 17028949
TI  - Accumulation of chloroplast DNA sequences on the Y chromosome of Silene
      latifolia.
AB  - Silene latifolia is a model dioecious plant with heteromorphic sex chromosomes.
      The Y chromosome is the largest in this species. Theoretical models propose an
      accumulation of repetitive DNA sequences in non-recombining parts of the Y
      chromosome. In this study, we isolated a BAC7H5 clone preferentially hybridizing
      to the Y chromosome of S. latifolia. Sequence analysis revealed that this BAC7H5
      contains part of the chloroplast genome, indicating that these chloroplast
      sequences have accumulated on the Y chromosome and also may contribute to its
      large size. We constructed Y chromosome- and X chromosome-specific libraries and
      screened them to find Y- and/or X-linked copies of chloroplast sequences.
      Sequence analysis revealed higher divergence of a non-genic region of the
      chloroplast sequences located on the Y chromosome while genic regions tested
      showed only very low (max 0.9%) divergence from their chloroplast homologues.

PMID- 17028950
TI  - Molecular phylogeny of black flies (Diptera: Simuliidae) from Thailand, using
      ITS2 rDNA.
AB  - The sequences of the second internal transcribed spacer (ITS2) of ribosomal DNA
      (rDNA) were determined for 40 black fly species from Thailand, belonging to 4
      subgenera of the genus Simulium, namely Gomphostilbia (12 species), Nevermannia
      (5 species), Montisimulium (1 species), Simulium sensu stricto (21 species), and
      an unknown subgenus with one species (Simulium baimaii). The length of the ITS2
      ranged from 247 to 308 bp. All black fly species had high AT content, ranging
      from 71 to 83.8%. Intraindividual variation (clonal variation) occurred in 13
      species, ranging from 0.3 to 1.1%. Large intrapopulation and interpopulation
      heterogeneities exist in S. feuerboni from the same and different locations in
      Doi Inthanon National Park, northern Thailand. Phylogenetic relationships among
      40 black fly species were examined using PAUP (version 4.0b10) and MrBAYS
      (version 3.0B4). The topology of the trees revealed two major monophyletic
      clades. The subgenus Simulium and Simulium baimaii were placed in the first
      monophyletic clade, whereas the subgenera Nevermannia + Montisimulium were placed
      as the sister group to the subgenus Gomphostilbia in the second monophyletic
      clade. Our results suggest that S. baimaii belongs to the malyschevi-group or
      variegatum-group in the subgenus Simulium. The molecular phylogeny generally
      agrees with existing morphology-based phylogenies.

PMID- 17028951
TI  - Tuareg, a novel miniature-inverted repeat family of pearl millet (Pennisetum
      glaucum) related to the PIF superfamily of maize.
AB  - Miniature-inverted repeat transposable elements (MITEs) are abundantly repeated
      in plant genomes and are especially found in genic regions where they could
      contribute regulatory elements for gene expression. We describe with molecular
      and cytological tools the first MITE family reported in pearl millet: Tuareg. It
      was initially detected in the pearl millet ortholog of Teosinte-branched1, an
      important developmental gene involved in the domestication of maize. The Tuareg
      family was amplified recently in the pearl millet genome and elements were found
      more abundant in wild than in domesticated plants. We found that they shared
      similarity in their terminal repeats with the previously described mPIF MITEs and
      that they are also present in other Pennisetum species, in maize and more
      distantly related grasses. The Tuareg family may be part of MITEs activated by
      PIF-like transposases and it could have been mobile since pearl millet
      domestication.

PMID- 17028952
TI  - Direct and correlated effects of selection on flight after exposure to thermal
      stress in Drosophila melanogaster.
AB  - To demonstrate how insects may adapt to ecologically relevant levels of heat
      stress, we performed artificial selection on the ability of Drosophila
      melanogaster to fly after an exposure to a high but non-lethal thermal stress.
      Both tolerance and intolerance to heat stress arose very quickly, as only a few
      generations of selection were necessary to cause significant separation between
      high and low lines for heat tolerance. Estimates of heritability based on the
      lines artificially selected for increased flight ability ranged from 0.024 to
      0.052, while estimates of heritability based on the lines selected for the
      inability to fly after heat stress varied between 0.035 and 0.091. Reciprocal F1
      crosses among these lines revealed strong additive effects of one or more
      autosomes and a weaker X-chromosome effect. This variation apparently affected
      flight specifically; neither survival to a more extreme stress nor knockdown by
      high temperature changed between lines selected for high and low heat tolerance
      as measured by flight ability. As the well-studied heat-shock response is
      associated with heat tolerance as measured by survival and knockdown, the aspects
      of the stress physiology that actually affect flight ability remains unknown.

PMID- 17028953
TI  - Genetic variation in two land snails, Cepaea nemoralis and Succinea putris
      (Gastropoda, Pulmonata), from sites differing in heavy metal content.
AB  - Allozyme variation was determined in two land snail species (Cepaea nemoralis and
      Succinea putris) from four localities in northern Belgium. In each locality we
      selected a polluted and a nearby, less-polluted, reference plot. We examined
      whether (i) genetic variability differed between the polluted and reference
      plots, (ii) populations from polluted plots experienced recent bottlenecks, and
      (iii) certain allele or genotype frequencies were associated with the pollution.
      Our results suggest that (i) about 13% of the genetic differentiation in C.
      nemoralis and 5% in S. putris was due to differences among polluted and reference
      plots, (ii) polluted and reference plots had comparable levels of genetic
      variation, but in C. nemoralis observed heterozygosities were higher in polluted
      plots, (iii) most plots showed significant evidence for recent bottlenecks,
      irrespective of the degree of pollution, so that bottlenecks seem poor indicators
      of pollution-induced stress in land snails, and (iv) mutagenic or pollution
      induced modifications did not seem to account for new allozyme variants in
      polluted sites. The observed patterns of genetic variation may be explained by
      the action of genetic drift, pollution-mediated selection, restricted gene flow,
      or a combination of these processes.

PMID- 17028954
TI  - FISH on avian lampbrush chromosomes produces higher resolution gene mapping.
AB  - Giant lampbrush chromosomes, which are characteristic of the diplotene stage of
      prophase I during avian oogenesis, represent a very promising system for precise
      physical gene mapping. We applied 35 chicken BAC and 4 PAC clones to both mitotic
      metaphase chromosomes and meiotic lampbrush chromosomes of chicken (Gallus gallus
      domesticus) and Japanese quail (Coturnix coturnix japonica). Fluorescence in situ
      hybridization (FISH) mapping on lampbrush chromosomes allowed us to distinguish
      closely located probes and revealed gene order more precisely. Our data extended
      the data earlier obtained using FISH to chicken and quail metaphase chromosomes 1
      6 and Z. Extremely low levels of inter- and intra-chromosomal rearrangements in
      the chicken and Japanese quail were demonstrated again. Moreover, we did not
      confirm the presence of a pericentric inversion in Japanese quail chromosome 4 as
      compared to chicken chromosome 4. Twelve BAC clones specific for chicken
      chromosome 4p and 4q showed the same order in quail as in chicken when FISH was
      performed on lampbrush chromosomes. The centromeres of chicken and quail
      chromosomes 4 seem to have formed independently after centric fusion of ancestral
      chromosome 4 and a microchromosome.

PMID- 17028955
TI  - Cytogenetic characterization of the sole Solea senegalensis (Teleostei:
      Pleuronectiformes: Soleidae): Ag-NOR, (GATA)n, (TTAGGG)n and ribosomal genes by
      one-color and two-color FISH.
AB  - A cytogenetic analysis of the sole Solea senegalensis was carried out using
      silver staining for the nucleolus organizer region (Ag-NOR) identification, one
      color FISH for chromosomal mapping of 45S and 5S ribosomal DNAs (rDNAs), (GATA)n,
      and (TTAGGG)n, and two-color FISH for co-localization of both rDNAs. The Ag-NORs
      and the 45S rDNA were mapped to a medium-sized submetacentric chromosomal pair.
      Hybridization with the 5S rDNA showed a major signal on the short arm of a medium
      sized submetacentric chromosome pair and a minor signal on a centromeric site of
      a small acrocentric chromosome pair. Differences in the Ag-NOR and 45S and 5S
      rDNAs FISH signal sizes were observed between homologous chromosomes and among
      individuals. A two-color FISH co-localized 45S and 5S rDNAs to a medium-sized
      submetacentric chromosomal pair. The hybridization with the telomeric (TTAGGG)n
      repeat displayed small signals at all chromosomal telomeres. Finally, the (GATA)n
      probe produced dispersed and small hybridization signals on all chromosome
      spreads, showing its ubiquitous existence in the genome. These results were
      compared with those from other Pleuronectiformes and discussed in terms of
      karyotype evolution.

PMID- 17028956
TI  - Long L1 insertions in human gene introns specifically reduce the content of
      corresponding primary transcripts.
AB  - LINE-1 (L1) retrotransposons comprise about 17% of the human genome and include a
      recently transposed set of Ta-L1 elements that are polymorphic in humans.
      Although it is widely believed that L1s play an essential role in shaping and
      functioning of mammalian genomes, the understanding of the impact of L1
      insertions on gene expression is far from being comprehensive. Here we compared
      hnRNA contents for allele pairs of genes heterozygous for Ta-L1 insertions in
      their introns in human cell lines of various origin. We demonstrated that some Ta
      L1 insertions correlated with decreased content of the corresponding hnRNAs. This
      effect was characteristic of only nearly full-sized L1s and seemed to be tissue
      specific.

PMID- 17028957
TI  - Genic heterozygosity, chromosomal interchanges and fitness in rye: any
      relationship?
AB  - Relationship between heterozygosity at allozyme loci, chromosomal interchanges
      and fitness was analyzed in a rye cultivar showing a polymorphism for such
      rearrangements. Nine allozyme systems (ACO, ACPH, GOT, GPI, LAP, MDH, PER, PGD
      and PGM) and five components of fitness (number of fertile tillers, total
      offspring, egg cell fertility, flowers/ear and seeds/ear) were studied. The
      estimated selection coefficients against interchange heterozygotes ranged from s
      = 0.12 to s = 0.34. A significant effect of the genic heterozygosity on some
      fitness components was observed in interchange heterozygotes (tillering and total
      offspring), in their standard homozygous sibs (flowers/ear and seeds/ear) and in
      the descendants of the crosses between standard karyotypes (flowers/ear,
      seeds/ear and egg cell fertility). However, the main effect was linked to genetic
      background associated to different crosses. Significant differences for Acph-1,
      Gpi-1, Lap-1, Mdh-1, Mdh-4, Pgd-2 and Pgm-1 loci were also found in some of these
      crosses although these differences were inconsistent. This suggests that probably
      the allozyme loci analyzed were not directly contributing to the fitness and that
      they are linked, in some cases, to different deleterious alleles depending on
      both cross and locus. This fact could support the local effect hypothesis as
      explanation although we do not discard the existence of some inbreeding level
      (general effect hypothesis) since all crosses and loci studied show a overall
      consistent trend of increased fitness with increased heterozygosity.

PMID- 17028958
TI  - Conservation of pBuM-2 satellite DNA sequences among geographically isolated
      Drosophila gouveai populations from Brazil.
AB  - In this study, we have compared 34 repetition units of pBuM-2 satellite DNA of
      individuals from six isolated populations of Drosophila gouveai, a cactophilic
      member of Drosophila buzzatii cluster (repleta group). In contrast to the results
      of previous morphological and molecular data, which suggest differentiation among
      the D. gouveai populations, the sequences and the cluster analysis of pBuM-2
      monomers showed that this repetitive element is highly conserved among the six D.
      gouveai populations (97.8% similarity), indicating a slow rate of evolution of
      pBuM-2 sequences at the population level. Probably, some homogenization
      mechanisms of tandem sequences, such as unequal crossing or gene conversion, have
      maintained the sequence similarity of pBuM-2 among D. gouveai populations.
      Alternatively, such a result may be associated with a functional role of pBuM-2
      sequences, although it is not understood at present.

PMID- 17028959
TI  - The dynamic gene expression from different genetic systems for protein and lysine
      contents of indica rice.
AB  - The dynamic expression of genes for protein and lysine contents of rice grain
      under different environments was carried out with time-dependent measures by
      using the developmental genetic models for quantitative traits of triploid
      endosperm in cereal crops. The results showed that the genetic effects,
      especially genotype x environment (GE) interaction effects from the genes
      expression of different genetic systems including triploid endosperm, cytoplasm
      and diploid maternal plant were important for the performance of both nutrient
      quality traits at all developmental times/stages of rice grain. The conditional
      genetic variance analysis found that the activation of quantitative genes
      especially from endosperm and maternal plant genetic systems for protein and
      lysine contents was gradually carried through the developmental process of rice
      grain. The net genetic effects showed that the new expression of quantitative
      genes for protein and lysine contents was more active at late filling stage (15
      21 days after flowering) and maturity stage (22-28 days) of rice grain. Also the
      sequential expression of cytoplasmic genes cannot be ignorable for the
      development of nutrient quality traits. The phenomena that some genes could
      continuously express for several developmental stages or the genes expression
      could be interrupted among developmental stages of rice grain was detected
      especially for net endosperm additive main effects or maternal additive main
      effects. The differences of genetic relationships from different genetic systems
      were found for protein and lysine contents among developmental times of rice
      grain.

PMID- 17028960
TI  - Seasonal dynamics of population genetic structure in cryptic taxa of the
      Pellioditis marina complex (Nematoda: Rhabditida).
AB  - The distribution patterns and genetic structure of the Pellioditis marina species
      complex in Belgium and The Netherlands were compared between four consecutive
      seasons. Different types of habitats (coast, estuary, semi-estuary and lake) with
      different degrees of connectivity were sampled. In addition, each habitat type
      was characterised by either temporal or permanent algal deposits. We screened 426
      bp of the mitochondrial cytochrome oxidase c (COI) gene with the single-strand
      conformation polymorphism (SSCP) method in 1615 individuals of Pellioditis
      marina. The 51 haplotypes were divided into four (sympatric) lineages, with
      divergences ranging from 0.25 to 10.6%. Our results show that the lineages have
      different temporal dynamics, which may be linked to abiotic factors. Analysis of
      Molecular Variance (AMOVA) indicated a significant structuring in the PmI
      lineage, which correlated with habitat characteristics and which changed over
      time (Mantel, r = 0.51; p = 0.126). Intrapopulational diversity was similar in
      all locations, and temporal changes in haplotype frequencies were not higher in
      temporary than in permanent algal deposits. Instead, the results of the temporal
      survey indicated that (some) P. marina populations are characterised by a
      metapopulation structure. It is emphasized that a complete and correct
      interpretation of processes causing genetic structuring within species and of the
      genetic structure itself can only be done when analyses are performed at several
      time points.

PMID- 17028961
TI  - RAPD variation and population genetic structure of Physalaemus cuvieri (Anura:
      Leptodactylidae) in Central Brazil.
AB  - Studies about the organization of the genetic variability and population
      structure in natural populations are used either to understand microevolutionary
      processes or the effects of isolation by human-inducted landscape modifications.
      In this paper, we analyzed patterns of genetic population structure using 126
      RAPD loci scored for 214 individuals of Physalaemus cuvieri, sampled from 18
      local populations. Around 97% of these loci were polymorphic. The among
      population variation component (Phi(ST)) obtained by AMOVA was equal to 0.101 and
      theta B obtained using a Bayesian approach for dominant markers was 0.103.
      Genetic divergence, analyzed by Mantel spatial correlogram, revealed only a short
      distance significant correlation between genetic and geographic distances. This
      is expected if low levels of population differentiation, due to high abundance
      buffering the effect of stochastic processes, are combined with low spatially
      restricted gene flow. Although this may be consistent with the current knowledge
      of species' biology, the spatial distribution of local populations observed in
      this study also suggest that, at least in part, recent human occupation and
      habitat fragmentation may also explain part of the interpopulational component of
      the genetic variation.

PMID- 17028962
TI  - Evolutionary chromosomal differentiation among four species of Conoderus
      Eschscholtz, 1829 (Coleoptera, Elateridae, Agrypninae, Conoderini) detected by
      standard staining, C-banding, silver nitrate impregnation, and CMA3/DA/DAPI
      staining.
AB  - The speciose Brazilian Elateridae fauna is characterized by high karyotypic
      diversity, including one species (Chalcolepidius zonatus Eschscholtz, 1829) with
      the lowest diploid number within any Coleoptera order. Cytogenetic analysis of
      Conoderus dimidiatus Germar, 1839, C. scalaris (Germar, 1824,) C. ternarius
      Germar, 1839, and C. stigmosus Germar, 1839 by standard and differential staining
      was performed with the aim of establishing mechanisms of karyotypic
      differentiation in these species. Conoderus dimidiatus, C. scalaris, and C.
      ternarius have diploid numbers of 2n(male) = 17 and 2n(female) = 18, and a X0/XX
      sex determination system, similar to that encountered in the majority of
      Conoderini species. The karyotype of C. stigmosus was characterized by a diploid
      number of 2n = 16 and a neoXY/neoXX sex determination system that was highly
      differentiated from other species of the genus. Some features of the mitotic and
      meiotic chromosomes suggest an autosome/ancestral X chromosome fusion as the
      cause of the neoXY system origin in C. stigmosus. C-banding and silver
      impregnation techniques showed that the four Conoderus species possess similar
      chromosomal characteristics to those registered in most Polyphaga species,
      including pericentromeric C band and autosomal NORs. Triple staining techniques
      including CMA3/DA/DAPI also provided useful information for differentiating these
      Conoderus species. These techniques revealed unique GC-rich heterochromatin
      associated with NORs in C. scalaris and C. stigmosus and CMA3-heteromorphism in
      C. scalaris and C. ternarius.

PMID- 17028963
TI  - Interplasmid transposition demonstrates piggyBac mobility in vertebrate species.
AB  - The piggyBac transposon is an extremely versatile helper-dependent vector for
      gene transfer and germ line transformation in a wide range of invertebrate
      species. Analyses of genome sequencing databases have identified piggyBac
      homologues among several sequenced animal genomes, including the human genome. In
      this report we demonstrate that this insect transposon is capable of
      transposition in primate cells and embryos of the zebrafish, Danio rerio.
      piggyBac mobility was demonstrated using an interplasmid transposition assay that
      has consistently predicted the germ line transformation capabilities of this
      mobile element in several other species. Both transfected COS-7 primate cells and
      injected zebrafish embryos supported the helper-dependent movement of tagged
      piggyBac element between plasmids in the characteristic cut-and-paste, TTAA
      target-site specific manner. These results validate piggyBac as a valuable tool
      for genetic analysis of vertebrates.

PMID- 17028964
TI  - High efficiency of a double-screening method on single P-element insertion lines
      to identify quantitative trait mutants in Drosophila melanogaster.
AB  - Enhancer trap P-element insertion has become a common method for generating new
      mutations in Drosophila melanogaster. When this method is used to isolate mutants
      for quantitative traits, an appropriate control must be established to define
      normal and mutant phenotypes. Considering that enhancer-trap lines are generated
      by crossing several strains, usually with no homogeneous genetic background, no
      clear control strain can be selected. Previous reports tried to overcome this
      problem by homogenizing the genetic background of the original lines. However,
      this is not the most common scenario, especially when functional phenotypes are
      studied in previously generated lines. Without such caution, is it possible to
      identify functional mutants among P-element insertion lines? We tested this for
      olfactory preference, a quantitative trait. Using as control measurement the
      average phenotype of 30 simultaneously generated P-element insertion lines with
      preferential reporter-gene expression in olfactory reception organs, we found
      that 25 of the lines exhibited mutant phenotypes in response to one or several of
      5 tested odorants. Additional tests showed that the efficiency of the method for
      detecting olfactory mutations exceeded 60% even for such a small number of tested
      odorants. According to these results this approach greatly facilitates the
      identification of putative abnormal phenotypes, which must be extensively
      confirmed afterwards.

PMID- 17028965
TI  - The association between inversion In(3R)Payne and clinally varying traits in
      Drosophila melanogaster.
AB  - In Drosophila melanogaster, inversion In(3R)Payne increases in frequency towards
      low latitudes and has been putatively associated with variation in size and
      thermal resistance, traits that also vary clinally. To assess the association
      between size and inversion, we obtained isofemale lines of inverted and standard
      karyotype of In(3R)Payne from the ends of the Australian D. melanogaster east
      coast cline. In the northern population, there was a significant association
      between In(3R)Payne and body size, with standard lines from this population being
      relatively larger than inverted lines. In contrast, the inversion had no
      influence on development time or cold resistance. We strengthened our findings
      further in a separate study with flies from populations from the middle of the
      cline as well as from the cline ends. These flies were scored for wing size and
      the presence of In(3R)Payne using a molecular marker. In females, the inversion
      accounted for around 30% of the size difference between cline ends, while in
      males the equivalent figure was 60%. Adaptive shifts in size but not in the other
      traits are therefore likely to have involved genes closely associated with
      In(3R)Payne. Because the size difference between karyotypes was similar in
      different populations, there was no evidence for coadaptation within populations.

PMID- 17028966
TI  - Genetic diversity and population structure of Lamiophlomis rotata (Lamiaceae), an
      endemic species of Qinghai-Tibet Plateau.
AB  - Lamiophlomis rotata (Lamiaceae), a perennial medicinal herb, is endemic to the
      Qinghai-Tibet Plateau. A total of 188 individuals from eight natural populations
      of L. rotata in Qinghai-Tibet Plateau (four from Tibet, two from Yunnan, and two
      from Qinghai) were analyzed using intersimple sequence repeats (ISSR) and
      randomly amplified polymorphic DNA (RAPD) techniques. Our results revealed that
      the level of genetic variation in L. rotata was relatively high (P = 94.85%, I =
      0.440 +/- 0.220, H(T) = 0.289 +/- 0.028). Three genetic groups corresponding to
      the three geographic regions were detected, suggesting significant geographic
      structure. Our results suggest that the highly structured geographic pattern
      found in L. rotata might represent diverging evolutionary processes associated
      with the uplifting of the Qinghai-Tibet Plateau and Quaternary climatic
      oscillations. These findings imply that as many populations as possible should be
      preserved in situ for the conservation of this species. Given their genetic
      variability and peripheral distribution, Qinghai and Yunnan populations should be
      assigned priority for conservation. Optimal harvesting strategies, domestication
      and tissue culture of L. rotata should be developed as soon as possible to
      guarantee its sustainable use.

PMID- 17028967
TI  - Isolation and characterization of a novel semi-lethal Arabidopsis thaliana mutant
      of gene for pentatricopeptide (PPR) repeat-containing protein.
AB  - A novel Arabidopsis thaliana mutant of one member of the pentatricopeptide repeat
      (PPR) gene family has been identified among T-DNA insertion lines. Tagging of the
      At1g53330 gene caused the appearance of a semi-lethal mutation with a complex
      phenotypic expression from embryo lethality associated with the abnormal pattern
      of cell division during globular to heart transition to fertile plants with just
      subtle phenotypic changes. The PPR protein At1g53330.1 was predicted to be
      targeted to mitochondria by TargetP and MitoProt programs. Complementation
      analysis confirmed that the phenotype is a result of a single T-DNA integration.
      A thorough functional analysis of this mutant aimed at finding a particular
      organelle target of At1g53330.1 protein will follow.

PMID- 17028968
TI  - High RAPD but no cpDNA sequence variation in the endemic and endangered plant,
      Heptacodium miconioides Rehd. (Caprifoliaceae).
AB  - Heptacodium miconioides Rehd. is an endangered species endemic to China and has
      suffered rapid decrease of distribution range and population size. This species
      has been disappeared in central China where the modal specimen was collected. We
      analyzed the genetic variation of the remaining populations to reveal whether the
      genetic diversity also suffered decrease and to provide some suggestions for
      conservation. All the nine known remaining populations were sampled. Genetic
      variation was analyzed based on RAPD markers and two fragments of cpDNA sequence,
      intergenic spacers of petG-trnP and trnS-trnG. No variation was observed in the
      two fragments of cpDNA sequence. However, the species exhibited high level of
      RAPD variation compared to other threatened or rare plants. Measures of genetic
      diversity within populations were strongly related to the log of estimated
      population size, indicating that large populations usually have more genetic
      diversity than that of small ones. About 25% of the variation was partitioned
      among populations. Significant relationship was observed between differentiation
      and geographical distance, indicating a pattern of isolation-by-distance. Given
      for few populations remaining, all the populations should be protected and urgent
      efforts be paid on the small populations to avoid their local extinction.

PMID- 17028969
TI  - Testing alternative methods for purging genetic load using the housefly (Musca
      domestica L.).
AB  - When a population faces long-term inbreeding, artificial selection, in principle,
      can enhance natural selection processes for purging the exposed genetic load.
      However, strong purge pressures might actually decrease fitness through the
      inadvertent fixation of deleterious alleles and allelic combinations. We tested
      lines of the housefly (Musca domestica L.) for the effectiveness of artificial
      selection to promote the adaptation to small population size. Specifically,
      replicate populations were held at average census sizes of 54 for nine
      generations or 30 for 14 generations while being subjected to artificial
      selection pressure for increased fitness in overall mating propensity (i.e., the
      proportion of virgin male-female pairs initiating copulation within 30 min),
      while also undergoing selection to create differences among lines in multivariate
      components of courtship performance. In the 14-generation experiment, a subset of
      the lines were derived from a founder-flush population (i.e., derived from three
      male-female pairs). In both experiments, we also maintained parallel non
      selection lines to assess the potential for natural purging through serial
      inbreeding alone. Sub-populations derived from a stock newly derived from the
      wild responded to artificial selection for increased mating propensity, but only
      in the short-term, with eventual rebounds back to the original levels. Serial
      inbreeding in these lines simply reduced mating propensity. In sub-populations
      derived from the same base population, but 36 generations later, both artificial
      selection and serial inbreeding increased mating propensity, but mainly to
      restore the level found upon establishment in the laboratory. Founder-flush lines
      responded as well as the non-bottlenecked controls, so we base our major
      conclusions on the comparisons between fresh-caught and long-term laboratory
      stocks. We suggest that the effectiveness of the alternative purge protocols
      depended upon the amount of genetic load already exposed, such that prolonged
      periods of relaxed or altered selection pressures of the laboratory rendered a
      population more responsive to purging protocols.

PMID- 17028970
TI  - Molecular evolution and functional specialization of chalcone synthase
      superfamily from Phalaenopsis orchid.
AB  - Plant genomes appear to exploit the process of gene duplication as a primary
      means of acquiring biochemical and developmental flexibility. The best example is
      the gene encoding chalcone synthase (CHS, EC2.3.1.74), the first committed step
      in flavonoid biosynthesis. In this study, we examined the molecular evolution of
      three CHS family members of Phalaenopsis including a novel chs gene (phchs5),
      which is slowly evolved. The inferred phylogeny of the chs genes of Phalaenopsis
      with other two orchid plants, Bromoheadia finlaysoniana and Dendrobium hybrid,
      suggested that gene duplication and divergence have occurred before divergence of
      these three genera. Relatively quantitative RT-PCR analysis identified expression
      patterns of these three chs genes in different floral tissues at different
      developmental stages. Phchs5 was the most abundantly expressed chs gene in floral
      organs and it was specifically transcribed in petal and lip at the stages when
      anthocyanin accumulated (stage1-4). Phchs3 and phchs4 were expressed at much
      lower levels than phchs5. Phchs3 was expressed in pigmented tissue (including
      lip, petal and sepal) at middle stages (stages 2-4) and in colorless reproductive
      tissue at late stage (stage 5). Phchs4 was only expressed in petal at earlier
      stages (stage 1-3) and in lip at middle stage (stage 4). These results present
      new data on differentiation of gene expression among duplicate copies of chs
      genes in Phalaenopsis.

PMID- 17028971
TI  - Morgane, a new LTR retrotransposon group, and its subfamilies in wheats.
AB  - Transposable elements are the main components of grass genomes, especially in
      Triticeae species. In a previous analysis, we identified a very short element,
      Morgane_CR626934-1; here we describe more precisely this unusual element.
      Morgane_CR626934-1 shows high sequence identity (until 98%) with ESTs belonging
      to other possible small elements, expressed under abiotic and biotic stress
      conditions. No putative functional polyprotein could be identified in all of
      these different Morgane-like sequences. Moreover, elements from the
      Morgane_CR626934-1 subfamily are found only in wheats and Agropyrum genomes and
      among these species, only Ae. tauschii and T. aestivum present a high copy number
      of these elements. They are highly conserved in wheat genomes (95.5%). Based on
      the uncommon characteristics of the described Morgane-like elements, we proposed
      to classify them in a new group within the Class I LTR retrotransposon, the
      Morgane group.

PMID- 17028972
TI  - Differential organellar inheritance in Passiflora's (Passifloraceae) subgenera.
AB  - Four chloroplast (cp), one mitochondrial (mt), and one ribosomal nuclear (ITS)
      DNA regions were studied in four artificial and one natural interspecific
      Passiflora hybrids. The ITS results confirmed their hybrid origin and all mtDNAs
      were maternally inherited. The same, however, was not true for cpDNA. The four
      hybrids (three artificial and one natural) derived from species of the Passiflora
      subgenus showed a cpDNA paternal inheritance, while the one involving taxa of the
      Decaloba subgenus gave evidence of maternal transmission. These results are of
      significance for the ongoing studies which are being performed on the molecular
      evolution of this genus and furnish important background for investigations aimed
      at clarifying the factors which determine cpDNA inheritance.

PMID- 17028973
TI  - Repetitive DNA sequences include retrotransposons in genomes of the
      Glomeromycota.
AB  - Twenty-five repetitive elements are first described in the genomes of the
      arbuscular mycorrhizal (AM) fungi Gigaspora margarita, Gig. rosea and Glomus
      mosseae. Nineteen repetitive DNA sequences isolated by genomic library screening
      and four by self-priming PCR had no homology to known DNA sequences, except for
      two Gig. margarita sequences and one Gig. rosea sequence which showed amino acid
      similarity to retrotransposons. Part of the Gig. rosea sequence was also similar
      to a DNA transposon. Two other retrotransposon sequences were isolated using PCR
      targeting of reverse transcriptase and ribonuclease H domains. Evidence is
      provided for three gypsy-like LTR retrotransposon and two non-LTR retrotransposon
      sequences in the AM fungal genomes. Four contain stop codons indicating that they
      cannot be active. Expression of three retrotransposons was not detected in
      germinating spores or intraradical hyphae of Gig. margarita. Southern blot
      analyses indicated that these three sequences are dispersed in the genome and
      that two are methylated. Sequence analysis of different GmarLTR1 copies showed
      they have undergone mutations by transitions, which may have been induced by
      cytosine methylation. Transposable elements may have played a major role in
      shaping genome structure and size during evolution of the Glomeromycota.

PMID- 17028974
TI  - Estimating effects of a single gene and polygenes on quantitative traits from a
      diallel design.
AB  - A genetic model is developed with additive and dominance effects of a single gene
      and polygenes as well as general and specific reciprocal effects for the progeny
      from a diallel mating design. The methods of ANOVA, minimum norm quadratic
      unbiased estimation (MINQUE), restricted maximum likelihood estimation (REML),
      and maximum likelihood estimation (ML) are suggested for estimating variance
      components, and the methods of generalized least squares (GLS) and ordinary least
      squares (OLS) for fixed effects, while best linear unbiased prediction, linear
      unbiased prediction (LUP), and adjusted unbiased prediction are suggested for
      analyzing random effects. Monte Carlo simulations were conducted to evaluate the
      unbiasedness and efficiency of statistical methods involving two diallel designs
      with commonly used sample sizes, 6 and 8 parents, with no and missing crosses,
      respectively. Simulation results show that GLS and OLS are almost equally
      efficient for estimation of fixed effects, while MINQUE (1) and REML are better
      estimators of the variance components and LUP is most practical method for
      prediction of random effects. Data from a Drosophila melanogaster experiment
      (Gilbert 1985a, Theor appl Genet 69:625-629) were used as a working example to
      demonstrate the statistical analysis. The new methodology is also applicable to
      screening candidate gene(s) and to other mating designs with multiple parents,
      such as nested (NC Design I) and factorial (NC Design II) designs. Moreover, this
      methodology can serve as a guide to develop new methods for detecting
      indiscernible major genes and mapping quantitative trait loci based on mixture
      distribution theory. The computer program for the methods suggested in this
      article is freely available from the authors.

PMID- 17028976
TI  - Is survivin expression nevertheless related to disease outcome in breast cancer?

PMID- 17028975
TI  - Hypoxia-inducible factor-1alpha correlates with MET and metastasis in node
      negative breast cancer.
AB  - The mechanism of tumor hypoxia promoting metastasis remains uncertain. Hypoxia
      inducible factor-1alpha (HIF-1alpha) is a key mediator of the cellular response
      to hypoxia and binds the met promoter, resulting in increased expression of MET.
      In breast cancer, MET overexpression is associated with death caused by
      metastatic disease. Aim of this study is to investigate the role of HIF-1alpha in
      MET expression and metastasis in lymph node negative breast cancer. We recruited
      a homogeneous cohort of 104 patients with T(1-2)N(0)M(0) breast carcinoma, who
      had undergone primary surgery. Fifty-three patients had distant metastases and 51
      patients had no evidence of disease for more than 10 years. We analyzed the
      expressions of HIF-1alpha and MET in these patients using immunohistochemistry.
      HIF-1alpha and MET were positively correlated (Spearman's rank correlation
      coefficient, 0.35; P < 0.01), were independent predictors of distant metastasis
      (P = 0.002 and P = 0.03, respectively), and correlated with poor 10-year disease
      free survival rate (P < 0.001 for both). Furthermore, co-overexpression of HIF
      1alpha and MET was a significant independent predictor of distant metastasis (odd
      radio, 10.78; P < 0.001), and patients with co-overexpression had a significantly
      worse 10-year disease-free survival rate. The results provide evidence that tumor
      hypoxia promotes metastasis through the induction of MET overexpression by HIF
      1alpha and emphasize the promising status of HIF-1alpha as a therapeutic target
      against metastasis in node-negative breast cancer.

PMID- 17028977
TI  - Simultaneous two-color spectral fluorescence lymphangiography with near infrared
      quantum dots to map two lymphatic flows from the breast and the upper extremity.
AB  - Due to their small size and poor access, the lymphatic function has been
      difficult to study in vivo. Especially difficult is the mapping of lymphatic
      drainage from two basins into the same node. Quantum dots can be used to perform
      multicolor images with high fluorescent intensity and are of a nano-size size
      suitable for lymphatic imaging via direct interstitial injection. Here we show
      simultaneous two-color in vivo wavelength-resolved spectral fluorescence
      lymphangiography using two near infrared quantum dots with different emission
      spectra, which allow non-invasive and simultaneous visualization of two separate
      lymphatic flows draining the breast and the upper extremity and variations in the
      drainage patterns and the water sheds within the axillary node. Two-color
      spectral fluorescence lymphangiography can provide insight into mechanisms of
      drainage from different lymphatic basins that may lead to sentinel lymph nodes
      detection of the breast cancer as well as prevention of complications such as
      lymphedema of the arm.

PMID- 17028978
TI  - Physician and patient characteristics associated with outpatient breast cancer
      screening recommendations in the United States: analysis of the National
      Ambulatory Medical Care Survey Data 1996-2004.
AB  - BACKGROUND: The primary goal of breast cancer screening tests is to find cancer
      at an early stage before a person has any symptoms. Evidence suggests that
      screening examinations such as mammography and clinical breast examinations (CBE)
      are effective in early detection of breast cancer. Physician recommendation is an
      important reason many women undergo screening. This study examined the physician
      and patients related factors associated with physician recommendations for breast
      cancer screening in the United States (US) outpatient settings. METHODS: This
      cross-sectional study used data from the National Ambulatory Medical Care Survey
      (NAMCS) from 1996-2004. Women aged >or=40 years were included in the study
      sample. Multivariate logistic regression analyses were used to study the
      objectives. RESULTS: Weighted analysis indicated that physicians performed 198
      million CBEs and made 110 million mammography recommendations over the study
      period (1996-2004). Patients' age, duration of visits, history of previous breast
      cancer diagnosis, and source of insurance were significant predictors of
      screening recommendations in this population. Obstetricians and gynecologists
      were more likely to perform a CBE and recommend mammography than other specialty
      physicians. CONCLUSIONS: These findings indicated that there were certain
      disparities regarding the physician recommendations of breast cancer screening
      for women in the US outpatient settings.

PMID- 17028979
TI  - Results from an observational trial with oral vinorelbine and trastuzumab in
      advanced breast cancer.
AB  - PURPOSE: We evaluated the efficacy and tolerability of oral vinorelbine plus
      trastuzumab (OV + T) in Her2 positive advanced breast cancer as first line
      chemotherapy or after progressing on earlier treatment. PATIENTS AND METHODS:
      Thirty consecutive patients (median age: 59 years) were included. Patients
      received OV in a dose of 60 mg/m(2) on day 1 and 8, q=21, without dose
      escalation. Trastuzumab was administered every 3 weeks at a dose of 6 mg/kg
      bodyweight after a loading dose of 8 mg/kg. Response was evaluated every three
      cycles using UICC criteria. Time to progression (TTP) and overall survival (OS)
      were estimated using the Kaplan-Meier product limit method. A multivariate
      analysis was performed to evaluate factors potentially influencing response rate
      and TTP. RESULTS: Median time of observation was 20 months. We observed a
      complete response in 18% of patients, partial remission in 50%, stable disease
      >or= 6 months in 21%, and progressive disease in 11%. TTP was median 9 months. OS
      was not reached. Response rate and TTP were influenced by line of treatment only.
      The main toxicities consisted of neutropenia and nausea. CONCLUSIONS: OV + T
      appears to be an effective and safe treatment option in advanced breast cancer at
      the dose and schedule chosen.

PMID- 17028980
TI  - Are there racial differences in breast cancer treatments and clinical outcomes
      for women treated at M.D. Anderson Cancer Center?
AB  - PURPOSE: To determine the influence of race on breast cancer treatment and on
      recurrence and breast cancer specific death. PATIENTS AND METHODS: The study
      population consisted of 6,054 African-American or white women who were diagnosed
      with breast cancer and received at least one of the treatments including
      mastectomy or breast conservative surgery, radiation, adjuvant chemotherapy, neo
      adjuvant chemotherapy, and adjuvant endocrine therapy at M.D. Anderson Cancer
      Center between June 1997 and February 2005. The clinical outcomes were disease
      free survival and breast-cancer-specific survival. Logistic regression analysis
      was performed to investigate if race was associated with the selection of each
      primary treatment while adjusting for tumor characteristics at diagnosis. Cox
      proportional hazards model was used to determine the effect of race on recurrence
      free survival and breast-cancer-specific survival controlling for tumor
      characteristics, presence of co-morbidity conditions and use of these treatments.
      RESULTS: The use of any primary treatment for breast cancer was not significantly
      different by race after adjusting for tumor characteristics and co-morbidity
      conditions. Although tumor characteristics at diagnosis explained the major
      differences in clinical outcomes, race remained an independent prognostic factor
      for breast-cancer-specific survival (P=0.002), and a marginally significant
      factor for disease-free survival (P=0.063) in multivariate analyses. CONCLUSION:
      Equal treatment may not lead to equal clinical outcomes given similar tumor
      characteristics at diagnosis. To reduce racial differences in breast cancer
      recurrence and survival, it is important to have a better understanding of
      differences in tumor biology by race and to promote the use of early detection
      programs among African-American women.

PMID- 17028981
TI  - 15-deoxy-Delta(12,14)-prostaglandin J2 inhibits G2-M phase progression in human
      breast cancer cells via the down-regulation of cyclin B1 and survivin expression.
AB  - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ(2)) exerts a growth inhibitory effect on cancer cells, and this effect is
      linked to the induction of apoptosis or cell cycle arrest. Induction of apoptosis
      by 15d-PGJ(2) is associated with the down-regulation of anti-apoptotic proteins.
      G(0)-G(1)-->S phase progression is inhibited by 15d-PGJ(2) via the degradation of
      cyclin D1. In this study, we further investigated the mechanism by which 15d
      PGJ(2) inhibits cancer cell growth by using the breast cancer cell lines MCF-7
      and T-47D. Treatment with 20 microM 15d-PGJ(2) for 72 h completely blocked the
      growth in both cell lines. However, the proportions of apoptotic MCF-7 and T-47D
      cells were 21.1% and 40.9%, respectively, indicating that the induction of
      apoptosis did not appear to fully account for growth inhibition by 15d-PGJ(2).
      Cell cycle analysis using cells synchronized at the G(0)-G(1) or S phase revealed
      that 15d-PGJ(2) blocked not only G(0)-G(1)-->S phase progression but also G(2)-M
      phase progression. The expression of both cyclins D1 and B1 was decreased by 15d
      PGJ(2). Furthermore, 15d-PGJ(2) inhibited aurora-B kinase activity, which
      coincided with the down-regulation of survivin. Thus, 15d-PGJ(2) induced cell
      cycle arrest at the G(2)-M phase via inhibition of cyclin B1 expression and
      aurora-B kinase activity. We conclude that survivin may be an important target
      for 15d-PGJ(2), and its down-regulation may lead to a decrease in aurora-B kinase
      activity.

PMID- 17028982
TI  - Common non-synonymous polymorphisms in the BRCA1 Associated RING Domain (BARD1)
      gene are associated with breast cancer susceptibility: a case-control analysis.
AB  - The BRCA1 Associated RING Domain (BARD1) gene has been identified as a high
      penetrance gene for breast cancer, whose germline and somatic mutations were
      reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer
      cases. BARD1 plays a crucial role in tumor repression, along with its
      heterodimeric partner BRCA1. In the current study, we tested the hypothesis that
      common non-synonymous polymorphisms in BARD1 are associated with breast cancer
      susceptibility in a case-control study of 507 patients with incident breast
      cancer and 539 frequency-matched cancer-free controls in Chinese women. We
      genotyped all three common (minor allele frequency (MAF)>0.10) non-synonymous
      polymorphisms (Pro24Ser, Arg378Ser, and Val507Met) in BARD1. We found that the
      BARD1 Pro24Ser variant genotypes (24Pro/Ser and 24Ser/Ser) and Arg378Ser variant
      homozygote 378Ser/Ser were associated with a significantly decreased breast
      cancer risk, compared with their wild-type homozygotes, respectively.
      Furthermore, a significant locus-locus interaction was evident between Pro24Ser
      and Arg378Ser (P(int )= 0.032). Among the 378Ser variant allele carriers, the
      24Pro/Pro wild-type homozygote was associated with a significantly increased
      breast cancer risk (adjusted OR=1.81, 95% CI=1.11-2.95), but the subjects having
      24Pro/Ser or Ser/Ser variant genotypes had a significantly decreased risk
      (adjusted OR=0.74, 95% CI=0.56-0.99). In stratified analysis, this locus-locus
      interaction was more evident among subjects without family cancer history, those
      with positive estrogen receptor (ER) and individuals with negative progesterone
      receptor (PR). These findings indicate that the potentially functional
      polymorphisms Pro24Ser and Arg378Ser in BARD1 may jointly contribute to the
      susceptibility of breast cancer.

PMID- 17028983
TI  - Changes in risk of death from breast cancer with season and latitude: sun
      exposure and breast cancer survival in Norway.
AB  - The Norwegian counties can conveniently be divided in three groups with different
      annual UV exposures and different incidence rates of squamous cell carcinoma
      (SCC) of the skin. In view of the hypothesis that latitude and season of
      diagnosis may play a role for breast cancer progression, the prognosis of breast
      cancer as determined for summer and winter diagnosis, were evaluated in the three
      residential regions. Two age groups were analysed separately (stratification at
      50 years). For all regions, and for all ages, the prognosis was best for women
      diagnosed in the summer season (Relative risk (RR) of death was 15-25% lower for
      summer diagnosis versus winter diagnosis). There was no significant seasonal
      variation of the number of new cases. For women diagnosed before the age of 50, a
      geographical gradient in cancer prognosis was also found (RR of death 0.6, 95%
      CI: 0.5-0.7 for cases diagnosed in southeast Norway and RR of death 0.8, 95% CI:
      0.6-1.1 for diagnosis in the north of Norway). This is in agreement with a 1.5
      times larger annual UV exposures and 3-4 times larger incidence rates of SCC in
      the southeast region when compared with the north region. For women diagnosed
      after the age of 50, no significant difference was found between the three
      regions. Despite a 17% higher vitamin D intake from food in north of Norway no
      difference in cancer survival was found for diagnosis during winter (when no
      significant differences in the levels of UV exposure can be detected between
      regions). The overall data support our earlier hypothesis that season of
      diagnosis and therapy start improves the survival for breast cancer.

PMID- 17028984
TI  - Paget's disease of the breast: accuracy of preoperative assessment.
AB  - BACKGROUND: Routine preoperative assessment may not accurately assess the extent
      of underlying cancer in patients with Paget's disease (PD) of the breast. We
      performed this study to correlate findings on clinical examination and
      mammography with pathologic results and outcomes in women with PD. METHODS: An
      IRB-approved retrospective review identified all patients with PD between 1975
      and 2000. Clinical exam and mammographic findings were recorded, and information
      on recurrence and survival was obtained from medical records. RESULTS: Univariate
      analyses identified palpable mass and suspicious mammogram as risk factors
      significantly associated with a worse outcome. Patients were therefore
      categorized by combinations of these two preoperative factors. All patients with
      a palpable mass and a suspicious mammogram had invasive cancer. In the subgroup
      of 40 women with a benign mammogram and no palpable mass, invasive cancer
      occurred in 5% and the majority (68%) had ductal carcinoma in situ which extended
      beyond the nipple. Women with a palpable mass and a suspicious mammogram had
      significantly worse survival compared to those with a benign mammogram and no
      palpable mass (P = 0.008). With a median follow-up of 6.4 years, five local
      recurrences occurred in patients with invasive cancer who underwent mastectomy.
      CONCLUSION: In women with PD, a palpable mass or suspicious mammogram portends a
      high likelihood of invasive cancer. Underlying cancer is common even in women
      with a benign mammogram and no palpable mass. Although breast conservation is an
      attractive option in patients with PD, mammography and physical exam may
      significantly underestimate the presence and extent of underlying disease.

PMID- 17028985
TI  - Improvement of best practice in early breast cancer: actionable surgeon and
      hospital factors.
AB  - To identify actionable elements for improving best practice, this study examined
      the relative effects of patient, surgeon and hospital factors on surgical
      treatment variation of 2,929 early breast cancer patients, diagnosed from January
      1998 to January 2002 in the region of the Comprehensive Cancer Centre North
      Netherlands. Multilevel logistic regression was used to analyze the
      hierarchically structured data. Apart from the patient level, 43.3% of the
      treatment variation was due to the hospital and 56.7% to the surgeon, after
      adjustment for patient characteristics. Although hospital factors like volume,
      teaching status, and management and policy contributed to this variation,
      multidisciplinary care seemed the most important actionable hospital factor.
      Although the surgeon was shown to be an important starting point for quality
      improvement, actionable elements seemed difficult to identify as factors like
      surgeon experience and volume were not conclusive and significant variance on
      this level remained (sigma2 = 0.149, SE 0.053). We conclude that
      multidisciplinary care can improve best practice and that further research into
      actionable surgeon factors is needed.

PMID- 17028986
TI  - Risk factors for breast cancer in older women: the relative contribution of bone
      mineral density and other established risk factors.
AB  - AIM: To determine the contribution of bone mineral density (BMD) to breast cancer
      risk relative to other established breast cancer risk factors in postmenopausal
      women with osteoporosis. METHODS: Data for this analysis comprised those
      collected from women randomized to placebo in the MORE and CORE trials (N =
      2,576). Risk factors measured at baseline included age, family history of breast
      cancer, estradiol level, body mass index, prior hormone therapy, BMD and
      vertebral fracture status. Cox proportional hazards regression models were used
      to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:
      Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers
      occurred. In univariate analyses, older age and family history of breast cancer
      were the strongest predictors of breast cancer risk, associated with a 2.4- and
      2.6-fold increase in breast cancer incidence. A higher estradiol level was
      associated with a 1.9-fold increase in breast cancer incidence. The association
      between femoral neck BMD and breast cancer incidence was only significant after
      adjustment for age (P = 0.03). The final multivariable model included age, family
      history, estradiol, BMD, and the BMD-estradiol interaction since the effect of
      BMD on breast cancer varied by estradiol level (interaction P-value, 0.04); in
      those with a lower estradiol level, a higher BMD was associated with a 2.6-fold
      increased in breast cancer. CONCLUSION: Overall, BMD is a relatively weak
      predictor of breast cancer risk in these postmenopausal women with osteoporosis,
      after taking into consideration age, family history and endogenous estradiol
      level.

PMID- 17028987
TI  - Legumain expression as a prognostic factor in breast cancer patients.
AB  - Invasive tumor cells and their microenvironments are enriched with a broad
      spectrum of different proteases. Legumain, a novel asparaginyl endopeptidase, has
      been observed to be highly expressed in several types of solid tumors. However,
      there is no data available identifying the relationship of legumain expression
      and clinicopathologic or biological variables in invasive breast cancer. For the
      first time, the prevalence of legumain expression in invasive breast cancer (n =
      432) and non-neoplastic breast tissues (n = 128) was investigated by
      immunohistochemistry. Three staining patterns were observed in the cytoplasm:
      diffuse positivity, tiny dots and vesicles. Whereas vesicular positivity in the
      majority of tumor cells was significantly correlated to an adverse outcome,
      cytoplasmic and dot-like staining showed no prognostic effect. Vesicular
      positivity was observed in 24% of carcinomas, but only in one case of non
      neoplastic breast tissue (<1%; proliferative mastopathy). This staining pattern
      was found to be independent of other factors analysed as grading, nodal status or
      HER2 expression. Besides being of prognostic value, legumain might prove to be an
      important predictive factor in breast cancer, since its unique cleavage
      specificity is already used in prodrug activation strategies.

PMID- 17028988
TI  - Correlates of physical activity level in breast cancer survivors participating in
      the Women's Healthy Eating and Living (WHEL) Study.
AB  - BACKGROUND: Physical activity levels among breast cancer survivors are typically
      low, and knowledge of the correlates of increased physical activity among cancer
      survivors is limited. The purpose of this study was to examine factors that are
      associated with physical activity or inactivity among breast cancer survivors.
      METHODS: Data from 3088 women participating in the Women's Healthy Eating and
      Living (WHEL) Study, collected prior to randomization, were the focus of the
      current analyses. Self-reports of physical activity levels, quality of life,
      depression, and dietary intakes were collected. Pearson correlation analyses were
      employed to examine the associations among these variables, and multiple
      regression analyses were performed to examine the relationship between selected
      health behaviors and physical activity levels, after controlling for demographic,
      breast cancer-related, and psychosocial variables. RESULTS: Demographic and
      psychosocial variables were related to physical activity levels (P < 0.001 for
      all). Cancer treatment type and cancer stage were correlated with survivors'
      physical activity levels (P < 0.01), but the associations were no longer
      significant after controlling for demographic variables. Physical activity levels
      were strongly associated with other health behaviors, especially dietary intakes
      (P < 0.001), even after controlling for demographic, cancer-related, and
      psychosocial factors. CONCLUSION: Low physical activity levels in breast cancer
      survivors are associated with specific behavioral and other factors, which can be
      considered as indicators of women at higher risk. Findings of significant
      differences in physical activity levels based on demographic characteristics
      suggest the importance of promoting physical activity particularly among breast
      cancer survivors of ethnic minority or lower education levels.

PMID- 17028989
TI  - Transcriptome analysis reveals an osteoblast-like phenotype for human osteotropic
      breast cancer cells.
AB  - Metastatic breast cancer cells exhibit the selective ability to seed and grow in
      the skeleton. We and others have previously reported that human breast tumors
      which metastasize to the skeleton overexpress bone matrix extracellular proteins.
      In an attempt to reveal the osteoblast-like phenotype of osteotropic breast
      cancer cells, we performed a microarray study on a model of breast cancer bone
      metastasis consisting of the MDA-MB-231 human cell line and its variant B02
      selected for its high capacity to form bone metastases in vivo. Analysis of B02
      cells transcriptional profile revealed that 11 and 9 out of the 50 most up- and
      down-regulated mRNAs, respectively, corresponded to genes which expression has
      been previously associated with osteoblastic differentiation process. Thus,
      osteoblast specific cadherin 11 which mediates the differentiation of mesenchymal
      cells into osteoblastic cells is up-regulated in B02. While S100A4, recently
      described as a key negative regulator of osteoblast differentiation, is the most
      down-regulated gene in B02 cells. RT-PCR and western blotting experiments allowed
      the validation of the modulation of several genes of interest. Using
      immunohistochemistry, performed on human breast primary tumors and their matched
      liver and bone metastases, we were able to confirm that the osteoblast-like
      pattern of gene expression observed in our model holds true in vivo. This is the
      first report demonstrating a gene-expression pattern corresponding to the
      acquisition of an osteomimetic phenotype by bone metastatic breast cancer cells.

PMID- 17028990
TI  - Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest
      and apoptosis in breast cancer cells.
AB  - 25-Hydroxy-3-oxoolean-12-en-28-oic acid (Amooranin-AMR) is a triterpene acid
      isolated from the stem bark of a tropical tree (Amoora rohituka) grown wild in
      India. A herbal preparation used for the treatment of cancer by the Ayurvedic
      system of medicine contains the stem bark of Amoora rohituka as one of the
      ingredients. In this paper, we show that AMR displays a strong inhibitory effect
      on survival of human breast carcinoma MDA-468, breast adenocarcinoma MCF-7 cells
      compared to breast epithelial MCF-10A control cells. A 50% decrease in cells
      (IC50) ranged from 1.8 to 14.6 microM and cell growth was suppressed by arresting
      cell cycle at G2 + M phase. AMR effectively induces apoptosis and triggered a
      series of effects associated with apoptosis including cleavage of caspase-8, -9, 
      3, Bid and ER stress in MDA-468 cells and caspase- 8, -9, -6 and Bid in MCF-7
      cells, release of cytochrome c from the mitochondria, cleavage of poly (ADP
      ribose) polymerase (PARP) and DNA fragmentation with a concomitant upregulation
      of p53, Bax and down-regulation of Bcl-2 in MDA-468 cells, but Bax unchanged in
      MCF-7 cells. The use of caspase blocking peptides and acridine orange staining
      confirmed the involvement of primarily caspase-9 and -3 in MDA-468 cells with
      mutated p53 and primarily caspase-8, -9 and -6 in MCF-7 cells expressing wt p53.
      We also observed in MCF-7/p53siRNA cells AMR treatment caused reduced expression
      of Bcl-2 without affecting levels of Bax similar to MCF-7 cells treated with AMR
      and proteolytic activation of Bax in MDA-468 cells. These results suggest that
      AMR induces apoptosis in human breast carcinoma cells via caspase activation
      pathway and likely it is a p53-independent apoptosis.

PMID- 17028991
TI  - Theoretical, developmental & cultural orientations of school-based prevention
      programs for preschoolers.
AB  - Schools are the primary environment in which to conduct prevention programs for
      school-age children. Educators, policy makers, and psychologist argue that
      prevention efforts should begin as early as possible to maximize their
      effectiveness. Surprisingly, there are relatively few school-based prevention
      programs targeted for preschoolers. Given the evidence supporting earlier rather
      than later prevention efforts and the fact that many children in the United
      States attend preschool programs, more research on the feasibility and
      effectiveness of prevention programs administered in preschool environments is
      warranted. In this article, we review the existing literature on school-based
      prevention programs targeted for preschool children. We examine whether school
      based prevention programs are theory driven, developmentally appropriate,
      culturally sensitive, and aimed specifically at symptom reduction or behavior
      promotion. Based on the findings of this review, our aim is to identify gaps in
      the prevention research literature regarding programs for preschoolers and
      propose research to address such gaps to create more effective school-based
      prevention programs for young children.

PMID- 17028992
TI  - Efficacy of a group medication adherence intervention among HIV positive women:
      the SMART/EST Women's Project.
AB  - This intervention sought to improve overall quality of life and health behavior
      in women living with human immunodeficiency virus (HIV). We contrasted the effect
      of a group cognitive behavioral stress management expressive supportive therapy
      (CBSM+) intervention plus a healthier lifestyles (HL) component with an
      individual educational/informational format plus HL on HIV-medication adherence.
      Women, n = 237, predominantly African-American and Latina, living with HIV were
      recruited from Miami, New York and New Jersey and randomized to group or
      individual conditions (ten weekly sessions) plus group or individual HL, i.e.,
      four conditions. Women reported relatively high levels of adherence at baseline.
      Participants in any of the group conditions increased self-reported adherence and
      emotion-focused coping skills in comparison with individual participation. This
      study suggests that group interventions may be an important adjunct in increasing
      medication adherence for HIV positive women.

PMID- 17028993
TI  - Development of a computer-based risk-reduction counseling intervention:
      acceptability and preferences among low-income patients at an urban sexually
      transmitted infection clinic.
AB  - In preparation for the development of an individually tailored, multimedia,
      computerized sexually transmitted infection (STI)/HIV-risk reduction intervention
      software application for use in publicly funded STI clinics, we conducted a
      waiting-room survey among 583 inner-city patients (67% male; 79% African
      American; mean age = 30.3) at an STI clinic in Milwaukee, Wisconsin regarding
      their computer experience and opinions related to a computerized approach to
      HIV/STI-risk reduction counseling. A substantial minority of respondents
      indicated they would prefer having either a combined computerized and human
      counseling intervention (30%) or preferred a computerized intervention alone
      (13%). Perceived benefits of computerized counseling included impartiality of the
      response, privacy, accuracy of the information, convenience, and being able to
      control the dissemination of information. Perceived disadvantages included lack
      of human contact, inability to obtain necessary information, technical problems,
      threats to privacy, and failure to take information from a computer seriously.
      Despite their limited economic resources, participants reported relatively high
      levels of computer experience overall and a willingness to use an individually
      tailored computerized risk-reduction counseling approach. We discuss how
      participants' responses were used to inform the development of such an
      intervention.

PMID- 17028994
TI  - A longitudinal study of adolescents with perinatally or transfusion acquired HIV
      infection: sexual knowledge, risk reduction self-efficacy and sexual behavior.
AB  - As HIV-positive children are surviving to adolescence and beyond, understanding
      their HIV knowledge and sexual behavior is critical. Forty HIV+ adolescents/young
      adults were interviewed twice, approximately 21 months apart (mean age 16.6 and
      18.3 years, respectively). Data on demographics, safer sex knowledge, sexual risk
      behaviors, risk reduction self-efficacy, and Tanner stage were collected. Twenty
      eight percent of HIV+ youth at Time 1 and 41% at Time 2 reported being sexually
      active. HIV transmission/safer sex knowledge was low, increased with age, and
      both self-efficacy for and actual condom use was relatively high. Secondary
      prevention messages should be incorporated into routine medical settings.

PMID- 17028995
TI  - A social cognitive model of health for HIV-positive adults receiving care in
      India.
AB  - In-depth interviews were conducted with 50 HIV-positive adults (23 women, 27 men)
      with access to care at a non-governmental organization in Chennai, India to gain
      a broad understanding of how they managed their HIV infection. Using a Social
      Cognitive Model of Health, we identified factors within the model's three domains
      -Personal, Environmental, and Behavioral--that are applicable to this socio
      cultural context. The Personal domain's factors were a positive self-concept,
      family-focused goals, and treatment optimism; the Environmental domain comprised
      family-based support, treatment availability, access and quality, and HIV stigma
      and discrimination; and the Behavior domain's factors were medication adherence
      and health habits, sexual behavior, and social relationships and emotional well
      being. Significant differences for many of the factors within the three domains
      were observed across married men and women, widowed women, unmarried men, and
      female sex workers. Implications for an enhanced intervention for HIV-infected
      individuals in similar treatment settings are discussed.

PMID- 17028996
TI  - The impact of chronic hepatitis C on health-related quality of life in homeless
      and marginally housed individuals with HIV.
AB  - Although infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus
      (HIV) frequently co-exist, there has been little research to determine the
      effects of HIV/HCV co-infection on health-related quality of life (HRQOL). We
      performed a cross-sectional analysis of baseline data from 216 participants
      enrolled in a community based study of HIV-infected homeless and marginally
      housed individuals, using multivariable linear regression analysis to determine
      if co-infection with HCV was independently associated with lower short-form 36
      (SF-36) questionnaire scores. We found that individuals with HCV had
      significantly lower mean SF-36 scores in the domains of physical functioning,
      bodily pain, social functioning and role limitation due to emotional health, and
      that HIV/HCV co-infection was independently associated with a lower physical
      component score but not a lower mental component score after controlling for
      numerous covariates. These results suggest that co-infection with HCV may have an
      adverse effect on HRQOL among homeless and marginally housed individuals with
      HIV.

PMID- 17028997
TI  - Evaluating the risk and attractiveness of romantic partners when confronted with
      contradictory cues.
AB  - Research shows that people engage in "risky" sex with "safe" partners and in
      "safer" sex with "riskier" partners. How is the determination of "risky" or
      "safe" status made? Factorial survey methodology was used to randomly construct
      descriptions of romantic partners based on attractive and/or risky
      characteristics. Respondents evaluated 20 descriptions for attractiveness, health
      risk, likelihood of going on a date, likelihood of unprotected sex, and
      likelihood of STD/HIV infection. Respondents were most attracted to and perceived
      the least risk from attractive descriptions and were least attracted to and
      perceived the most risk from the risky descriptions. The differences between the
      "conflicting information" descriptions are attributable to a primacy effect:
      descriptions that began with attractiveness information but end with risk
      information were evaluated more positively than those that began with risk and
      ended with attractive information.

PMID- 17028998
TI  - Developing a partnership model for cancer screening with community-based
      organizations: the ACCESS breast cancer education and outreach project.
AB  - There is growing enthusiasm for community-academic partnerships to promote health
      in underserved communities. Drawing upon resources available at a comprehensive
      cancer center, we developed the ACCESS program to guide community based
      organizations through a flexible program planning process. Over a three-year
      period, ACCESS partnered with 67 agencies serving various medically underserved
      populations. Organizations included hospitals, parishes, senior centers, harm
      reduction programs, and recreational facilities. Program outcomes at the
      organizational level were quantified in terms of introduction of new cancer
      information, referral or screening programs, as well as organizational capacity
      building. ACCESS represents a viable model for promoting partnership to transfer
      behavioral health programs and adapt interventions for new audiences. Plans to
      further evaluate and enhance this model to promote cancer screening efforts are
      discussed. We argue that, ultimately, formation and development of community
      partnerships need to be understood as a fundamental area of practice that must be
      systematically integrated into the mission of major academic medical institutions
      in every area of public health.

PMID- 17028999
TI  - A comparison of two recorders for obtaining in-flight heart rate data.
AB  - : Measurement of mental workload has been widely used for evaluation of aircraft
      design, mission analysis and assessment of pilot performance during flight
      operations. Heart rate is the psychophysiological measure that has been most
      frequently used for this purpose. The risk of interference with flight safety and
      pilot performance, as well as the generally constrained access to flights, make
      it difficult for researchers to collect in-flight heart rate data. Thus, this
      study was carried out to investigate whether small, non-intrusive sports
      recorders can be used for in-flight data collection for research purposes. Data
      was collected from real and simulated flights with student pilots using the Polar
      Team System sports recorder and the Vitaport II, a clinical and research
      recording device. Comparison of the data shows that in-flight heart rate data
      from the smaller and less intrusive sports recorder have a correlation of.981
      with that from the clinical recorder, thus indicating that the sports recorder is
      reliable and cost-effective for obtaining heart rate data for many research
      situations.

PMID- 17029000
TI  - Reducing drug costs at a Veterans Affairs hospital by increasing market-share of
      generic fluoxetine.
AB  - We previously showed that a multifaceted intervention designed to contain costs
      of prescribing selective serotonin reuptake inhibitors (SSRIs) at a Veterans
      Affairs hospital resulted in substantial projected savings. Intervention
      components included clinician education and pharmacy and computer information
      process changes. We now report on effects of altering the intervention to promote
      prescribing of generic fluoxetine. Over 30 months, fluoxetine's market-share
      increased from 12 to 32% of all SSRIs prescribed. A total of $2,500,000 in cost
      avoidance resulted from substituting generic for brand fluoxetine, and $600,000
      resulted from increases in market-share of fluoxetine. The results highlight the
      robustness and flexibility of the intervention approach.

PMID- 17029001
TI  - Genes and the environment in neurodegeneration.
AB  - Neurodegenerative diseases are a heterogeneous group of pathologies which
      includes complex multifactorial diseases, monogenic disorders and disorders for
      which inherited, sporadic and transmissible forms are known. Factors associated
      with predisposition and vulnerability to neurodegenerative disorders may be
      described usefully within the context of gene-environment interplay. There are
      many identified genetic determinants for neurodegeneration, and it is possible to
      duplicate many elements of recognized human neurodegenerative disorders in animal
      models of the disease. However, there are similarly several identifiable
      environmental influences on outcomes of the genetic defects; and the course of a
      progressive neurodegenerative disorder can be greatly modified by environmental
      elements. In this review we highlight some of the major neurodegenerative
      disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral
      sclerosis, Huntington's disease, and prion diseases.) and discuss possible links
      of gene-environment interplay including, where implicated, mitochondrial genes.

PMID- 17029003
TI  - Cell biological and biophysical aspects of lipid-mediated gene delivery.
AB  - Cationic lipids are conceptually and methodologically simple tools to deliver
      nucleic acids into the cells. Strategies based on cationic lipids are viable
      alternatives to viral vectors and are becoming increasingly popular owing to
      their minimal toxicity. The first-generation cationic lipids were built around
      the quaternary nitrogen primarily for binding and condensing DNA. A large number
      of lipids with variations in the hydrophobic and hydrophilic region were
      generated with excellent transfection efficiencies in vitro. These cationic
      lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in
      the last decade delineated the cell biological basis of the cationic lipid gene
      delivery to a significant detail. The application of techniques such as small
      angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking
      the physical properties of lipid:DNA complex (lipoplex) with its intracellular
      fate. This biological knowledge has been incorporated in the design of the second
      generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective
      strategies to overcome the various cellular barriers along with the lipoplex
      formulations methodologies. In this context, cationic lipid-mediated gene
      delivery is considerably benefited by the methodologies of liposome-mediated drug
      delivery. Lipid mediated gene delivery has an intrinsic advantage of being a
      biomimetic platform on which considerable variations could be built to develop
      efficient in vivo gene delivery protocols.

PMID- 17029002
TI  - Studies on the critical micellar concentration and phase transitions of
      stearoylcarnitine.
AB  - The critical micellar concentration (CMC) of stearoylcarnitine was determined at
      different pH values at room temperature by fluorescence spectroscopy, monitoring
      the spectral changes of 8-anilinonaphthalene-1-sulfonate (ANS). The CMC was found
      to vary with pH, increasing from about 10 microM at pH 3.0 to ca. 25 microM at pH
      7.0, but decreasing slightly with further increase in pH to approximately 19
      microM at pH 10.0. Differential scanning calorimetry (DSC) shows that
      stearoylcarnitine dispersed in water at low concentration undergoes a broad
      thermotropic phase transition at 44.5 degrees C, with a transition enthalpy of
      15.0 kcal/mol. The transition temperature (Tt) shifts to ca. 50.5 degrees C in
      the presence of 1 mM EDTA or when the concentration is increased significantly.
      The turbidity of aqueous dispersions of stearoylcarnitine was found to be
      considerably high at low temperatures, which decreases quite abruptly over a
      short temperature range, indicating that a transition occurs from a phase of
      large aggregates to one of much smaller aggregates, most likely micelles. The
      phase transition temperature was determined as 29.1 degrees C at pH 3.0, which
      increased with increasing pH up to a value of 55.3 degrees C at pH 8.6 and
      remains nearly constant thereafter up to pH 11.2. The pH dependence of CMC and Tt
      suggest that the pKa of the carboxyl group of long chain acylcarnitines shifts to
      higher temperatures upon aggregation (micelles or bilayer membranes).

PMID- 17029004
TI  - Spectrin organization and dynamics: new insights.
AB  - Spectrin is the major constituent protein of the erythrocyte cytoskeleton which
      forms a filamentous network on the cytoplasmic face of the membrane by providing
      a scaffold for a variety of proteins. In this review, several aspects of spectrin
      organization are highlighted, particularly with respect to its ability to bind
      hydrophobic ligands and its interaction with membrane surfaces. The
      characteristic binding of the fluorescent hydrophobic probes Prodan and pyrene to
      spectrin, which allows an estimation of the polarity of the hydrophobic probe
      binding site, is illustrated. In addition, the contribution of uniquely localized
      and conserved tryptophan residues in the 'spectrin repeats' in these processes is
      discussed. A functional implication of the presence of hydrophobic binding sites
      in spectrin is its recently discovered chaperone-like activity. Interestingly,
      spectrin exhibits residual structural integrity even after denaturation which
      could be considered as a hallmark of cytoskeletal proteins. Future research could
      provide useful information about the possible role played by spectrin in cellular
      physiology in healthy and diseased states.

PMID- 17029005
TI  - Stopped-flow kinetic studies of the interaction of bovine folate binding protein
      (FBP) and folate.
AB  - The kinetics of the interaction of bovine folate binding protein and folate at pH
      7.4 and 5.0 were followed by measuring the changes of the intrinsic protein
      fluorescence intensity using the stopped-flow technique, which enables the study
      of reactions from the millisecond time-range. Our results immediately reject a
      simple one-step binding model, which requires a linear dependence of the observed
      rate constant on the concentration of the ligand. Thus, we are able to conclude
      that at pH 5.0 the interaction occurs in two steps and at pH 7.4 in three steps.
      Changes of fluorescence spectra at equilibrium were used to estimate the overall
      binding constants. Comparative studies on the binding of folate to human albumin
      are also reported.

PMID- 17029006
TI  - Modulation of antigenic phenotype in cultured human osteoblast-like cells by
      FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta, LPS and IFNgamma.
AB  - BACKGROUND/AIMS: Recent reports demonstrated that osteoblast-like cells can also
      exert activities directly associated with the immune system (cytokine synthesis,
      antigen presentation, phagocytosis and stimulation of T lymphocytes). The present
      study aimed to analyze the effect of Transforming growth factorbeta1 (TGFbeta1),
      Fibroblast growth factor basic (FGFb), Platelet-derived growth factor-BB (PDGF
      BB), Interleukin-1beta (IL-1beta), Interleukin-2 (IL-2), Lipopolysaccharide (LPS)
      and Interferon-gamma (IFNgamma) on the expression on osteoblast-like cells of
      antigens involved in antigen presentation. METHODS: Flow cytometry was used to
      investigate whether the growth factors FGFb, TGFbeta1, PDGF-BB, IL-2, IL-1beta,
      LPS and IFNgamma modulate the expression on cultured human osteoblast-like cells
      of different antigens involved in antigen-presentation and T cell activation.
      RESULTS: TGFbeta1 treatment significantly reduced the expression of CD54 and
      CD86. IL-1beta treatment significantly enhanced the expression of CD54, CD86 and
      HLA-DR. LPS and IFNgamma treatments produced a major increase in CD54, CD80, CD86
      and HLA-DR expression. Expression of these antigen-presenting molecules was not
      significantly modified by FGFb, PDGF-BB or IL-2 treatment.

PMID- 17029007
TI  - A novel agent, methylophiopogonanone B, promotes Rho activation and tubulin
      depolymerization.
AB  - Cytoskeletal reorganization, including reconstruction of actin fibers and
      microtubules, is essential for various biological processes, such as cell
      migration, proliferation and dendrite formation. We show here that
      methylophiopogonanone B (MOPB) induces cell morphological change via melanocyte
      dendrite retraction and stress fiber formation. Since members of the Rho family
      of small GTP-binding proteins act as master regulators of dendrite formation and
      actin cytoskeletal reorganization, and activated Rho promotes dendrite retraction
      and stress fiber formation, we studied the effects of MOPB on the small GTPases
      using normal human epidermal melanocytes and HeLa cells. In in vitro binding
      assay, MOPB significantly increased GTP-Rho, but not GTP-Rac or GTP-CDC42.
      Furthermore, a Rho inhibitor, a Rho kinase inhibitor and a small GTPase inhibitor
      each blocked MOPB-induced stress fiber formation. The effect of MOPB on actin
      reorganization was blocked in a Rho dominant negative mutant. These results
      suggest MOPB acts via the Rho signaling pathway, and it may directly or
      indirectly activate Rho. Quantitative Western blot analysis indicated that MOPB
      also induced microtubule destabilization and tubulin depolymerization. Thus, MOPB
      appears to induce Rho activation, resulting in actin cytoskeletal reorganization,
      including dendrite retraction and stress fiber formation.

PMID- 17029009
TI  - Feeling strained? Influence of genetic background on depression-related behavior
      in mice: a review.
AB  - Depression is a growing pandemic in developed societies. The use of inbred mouse
      strains in pre-clinical psychiatric research has proven to be a valuable
      resource. Firstly, they provide the background for genetic manipulations that aid
      in the discovery of molecular pathways that may be involved in major depression.
      Further, inbred mouse strains are also being used in the determination of genetic
      and environmental influences that may pre-dispose or trigger depression-related
      behavior. This review aims to highlight the utility of inbred mouse strains in
      depression research, while providing an overview of the current state of research
      into behavioral differences between strains in paradigms commonly used in the
      field. Neurochemical differences that may underlie strain differences are
      examined, and some caveats and cautions associated with the use of inbred strains
      are highlighted.

PMID- 17029008
TI  - Podophyllum hexandrum modulates gamma radiation-induced immunosuppression in
      Balb/c mice: implications in radioprotection.
AB  - Aqueous extract of Podophyllum hexandrum (RP-1), which has been reported to
      render more than 82% survival against whole body lethal (10 Gy) gamma-irradiation
      in mice, was further investigated for its immunomodulatory potential. In this
      study, no significant change could be scored in peritoneal macrophages survival
      up to 8th day after whole body irradiation. RP-1 treatment (200 mg/kg body
      weight, i.p.) alone or 2 h before whole body irradiation enhanced macrophage
      survival significantly (p<0.05) as compared to irradiated control mice. In
      irradiated animals, there was significant (p<0.01) reduction in splenocyte
      survival and proliferation as revealed by 3H-TdR method. RP-1 treatment (200
      mg/kg) alone or 2 h before irradiation countered the decrease in survival of
      splenocytes and proliferation significantly (p<0.05) as compared to irradiated
      control group. Whole body irradiation also significantly (p<0.05) reduced the
      population of CD4+ and CD8+ T cells and bone marrow GM-CFU at 24 h and 72 h post
      irradiation intervals, respectively, as compared to unirradiated control. RP-1
      treatment 2 h before whole body irradiation countered the decrease in CD4+ and
      CD8+ T cells populations and CGM-CFU. Nitric oxide free radicals generation was
      enhanced significantly (p<0.05) in the supernatant of peritoneal macrophage
      cultures exposed to 2 Gy gamma radiation ex vivo in comparison to unirradiated
      control, which was reduced by pre-irradiation (-2 h) administration of RP-1.
      Whole body irradiation (10 Gy) also reduced the serum titres of IL-3, IL-1 and
      various IgG isotypes observed at different post-irradiation time interval. RP-1
      treatment alone or before whole body irradiation countered radiation induced
      decrease in the titre of IL-1, IL-3 and IgG's in the serum of mice. These
      findings indicate immunostimulatory potential of RP-1.

PMID- 17029014
TI  - Diffusion MRI in the early diagnosis of malignant glioma.
AB  - OBJECTIVE: A subset of patients with malignant glioma comes to medical attention
      before their masses show rim enhancement and central necrosis. Tumors in those
      cases are frequently located in eloquent areas of the brain. Tissue diagnosis is
      limited to stereotactic biopsy providing limited material for accurate grading.
      We conducted this study to determine whether imaging characteristics of early
      stages of malignant gliomas could aid in timely definitive diagnosis. METHODS: We
      retrospectively analyzed patients with newly diagnosed malignant glioma seen at
      the Yale Brain Tumor Center between 2002 and 2005. Patients with typical
      radiographic presentation were excluded. RESULTS: Of 89 patients, eight meeting
      the inclusion criteria were identified. In five patients, patchy or small nodular
      enhancing lesions without central necrosis were present within the tumor mass.
      Diffusion-weighted imaging (DWI) showed areas of increased signal intensity in
      all cases. Apparent diffusion coefficient maps (ADC) revealed low-signal
      intensity in corresponding areas. At the time of imaging, biopsy was performed in
      seven patients but diagnosis of malignant glioma could only be established prior
      to further tumor growth in four cases. CONCLUSIONS: The diagnosis in the early
      stages of malignant glioma can be challenging in a subset of cases. Information
      obtained through DWI should be incorporated in the clinical decision-making
      process. Mass lesions displaying decreased water diffusion indicating high
      cellularity, are suggestive of a high-grade glioma. Biopsies are recommended.
      However, even when biopsies are inconclusive, a strong suspicion of malignant
      glioma should be considered.

PMID- 17029015
TI  - Huge lobar intracerebral hemorrhage by glioblastoma multiforme.

PMID- 17029016
TI  - Profound effects of the general anesthetic etomidate on oxidative phosphorylation
      without effects on their yield.
AB  - We investigated the effects of the general anesthetic Etomidate on oxidative
      phosphorylation in isolated rat liver mitochondria. The study of each electron
      transfer site shows that there is an inhibition: mainly at complex I but also, to
      a lesser extent, at complex III. Moreover, with succinate as substrate, the
      increase in non-phosphorylating respiration is accompanied by a decrease in
      DeltaPsi. However, this effect is not due to classical uncoupling of oxidative
      phosphorylation, since ADP addition at high Etomidate concentrations restores the
      transmembrane difference of electrical potential. Also, in the same range of
      Etomidate concentration, the ATP/O ratio is not significantly affected. In
      conclusion, the main effect of Etomidate is to decrease the oxidative
      phosphorylation rate without changing yield. The H(+) leak which appears under
      non-phosphorylating conditions becomes negligible in physiological conditions.

PMID- 17029017
TI  - Gestalt perception and local-global processing in high-functioning autism.
AB  - This study examined gestalt perception in high-functioning autism (HFA) and its
      relation to tasks indicative of local visual processing. Data on of gestalt
      perception, visual illusions (VI), hierarchical letters (HL), Block Design (BD)
      and the Embedded Figures Test (EFT) were collected in adult males with HFA,
      schizophrenia, depression and normative controls. Individuals with HFA processed
      gestalt stimuli less in accord with gestalt laws, particularly regarding the
      principle of similarity. Gestalt processing correlated positively with global
      processing of the HL. EFT and BD performance correlated negatively with VI
      susceptibility in HFA. All clinical groups succumbed less to VI than the
      normative sample. Results suggest decreased gestalt perception in HFA, being
      associated with a more general local visual processing bias.

PMID- 17029018
TI  - Slowing down presentation of facial movements and vocal sounds enhances facial
      expression recognition and induces facial-vocal imitation in children with
      autism.
AB  - This study examined the effects of slowing down presentation of facial
      expressions and their corresponding vocal sounds on facial expression recognition
      and facial and/or vocal imitation in children with autism. Twelve autistic
      children and twenty-four normal control children were presented with emotional
      and non-emotional facial expressions on CD-Rom, under audio or silent conditions,
      and under dynamic visual conditions (slowly, very slowly, at normal speed) plus a
      static control. Overall, children with autism showed lower performance in
      expression recognition and more induced facial-vocal imitation than controls. In
      the autistic group, facial expression recognition and induced facial-vocal
      imitation were significantly enhanced in slow conditions. Findings may give new
      perspectives for understanding and intervention for verbal and emotional
      perceptive and communicative impairments in autistic populations.

PMID- 17029019
TI  - Brief report: perception of body posture--what individuals with autism spectrum
      disorder might be missing.
AB  - Autism has been associated with atypical face and configural processing, as
      indicated by the lack of a face inversion effect (better recognition of upright
      than inverted faces). We investigated whether such atypical processing was
      restricted to the face or extended to social information found in body postures.
      An inversion paradigm compared recognition of upright and inverted faces, body
      postures, and houses. Typical adults demonstrated inversion effects for both
      faces and body postures, but adults with autism demonstrated only a face
      inversion effect. Adults with autism may not have a configural processing deficit
      per se, but instead may have strategies for recognizing faces not used for body
      postures. Results have implications for therapies employing training in imitation
      and body posture perception.

PMID- 17029020
TI  - Autism in the Faroe Islands: an epidemiological study.
AB  - The Faroe Islands are considered to be a genetic isolate. This population study
      of the prevalence of autism sought to identify a representative cohort for future
      genetic studies. In 2002 all schools were screened for autism spectrum disorders.
      The target population were all children born in 1985 through 1994 and living in
      the Faroe Islands on December 31, 2002. Children who screened positive for autism
      characteristics were examined using the Diagnostic Interview for Social and
      Communication Disorders (DISCO). Of the children aged 8 through 17 years, 0.56%
      had childhood autism, Asperger syndrome or atypical autism. The male:female ratio
      was just under 6:1. The prevalence of autism in the Faroe Islands was very
      similar to that reported from many western countries.

PMID- 17029021
TI  - What is the most appropriate energy source for aortic cusp ablation? A comparison
      of standard RF, cooled-tip RF and cryothermal ablation.
AB  - BACKGROUND: Certain tachycardias can be eliminated by catheter ablation from
      within the base of the aortic valve (AV) cusps but the high blood flow and
      proximity to the coronary arteries create unique challenges. Standard
      radiofrequency (RF) energy, cooled-tip RF energy or cryothermal energy were
      compared to determine the optimal ablation modality. MATERIALS AND METHODS:
      Experiments were conducted using adult swine or goats (15 animals). Ablation
      lesions were placed using either: temperature-controlled RF (4 mm-tip catheter;
      60 degrees C/60 s), cooled-tip RF (4 mm-tip catheter with internal saline
      circulation at 0.6 ml/s; 40 degrees C/60 s), or cryoablation (6 mm-tip spot
      cryocatheter; <-75 degrees C/4 min). Animals were sacrificed 1 h after the last
      application and lesions were subject to pathological analysis. RESULTS: Standard
      RF and cryoablation created similar depth lesions in the right coronary cusp
      (4.2+/-1.3 and 3.4+/-0.5 mm, respectively) but cryoablation was unable to create
      any visible lesions in the non-coronary cusp. Cooled tip ablation created larger
      ablation lesions in the right coronary cusp (5.25+/-0.5) and fully transmural
      left atrial ablation lesions after ablation in the noncoronary cusp. Acute damage
      to the cusps was not noted with any ablation modality. Disruption of elastic
      fibers in the aortic media was seen after standard and cooled tip radiofrequency
      ablation but not cryoablation. CONCLUSION: Cryoablation within the AV cusps
      created similar sized lesions to standard RF ablation without evidence of elastic
      fibre disruption and may therefore be an appropriate first line ablation
      modality. Cooled-tip ablation created larger ablation lesions and therefore may
      be required if cryoablation is ineffective.

PMID- 17029022
TI  - Bone morphogenetic proteins and their antagonists.
AB  - Skeletal homeostasis is determined by systemic hormones and local factors. Bone
      morphogenetic proteins (BMPs) are unique because they induce the commitment of
      mesenchymal cells toward cells of the osteoblastic lineage and also enhance the
      differentiated function of the osteoblast. BMP activities in bone are mediated
      through binding to specific cell surface receptors and through interactions with
      other growth factors. BMPs are required for skeletal development and maintenance
      of adult bone homeostasis, and play a role in fracture healing. BMPs signal by
      activating the mothers against decapentaplegic (Smad) and mitogen activated
      protein kinase (MAPK) pathways, and their actions are tempered by intracellular
      and extracellular proteins. The BMP antagonists block BMP signal transduction at
      multiple levels including pseudoreceptor, inhibitory intracellular binding
      proteins, and factors that induce BMP ubiquitination. A large number of
      extracellular proteins that bind BMPs and prevent their binding to signaling
      receptors have emerged. The extracellular antagonists are differentially
      expressed in cartilage and bone tissue and exhibit BMP antagonistic as well as
      additional activities. Both intracellular and extracellular antagonists are
      regulated by BMPs, indicating the existence of local feedback mechanisms to
      modulate BMP cellular activities.

PMID- 17029024
TI  - Price vs. quantity in health insurance reimbursement.
AB  - While "integrated" systems regulate the quantity of health services,
      "Bismarckian" systems regulate their price. This paper compares the consumers'
      allocations implemented within the two reimbursement systems. In the model,
      illness has a negative impact on labor productivity while public insurance is
      financed through income tax. Consumers have private information with respect to a
      parameter which can be interpreted as heterogeneity either in intensity of their
      preferences for treatment or in the type of illness. The social planner may be
      constrained to adopt uniform insurance plans, or may be free to choose self
      selecting plans. The analysis of uniform plans shows that Bismarckian systems
      dominate integrated systems from the social welfare point of view; whereas the
      opposite ranking holds with self-selecting plans.

PMID- 17029025
TI  - Reconceptualizing the case management relationship in intensive treatment: a
      study of staff perceptions and experiences.
AB  - The helping relationship or alliance is theorized to be an important process
      variable in case management services for people with serious mental illness.
      Previous studies of the case management relationship borrow concepts and measures
      from psychotherapy research and therefore may overlook important differences in
      tasks, settings, and clinical roles across settings. A study of client-provider
      relationships as perceived by case managers, based on a qualitative study of two
      intensive case management (ICM) teams, is presented. The findings, which
      delineate positive and negative experiential elements, may be used to improve
      measurement of the case management relationship in future research.

PMID- 17029027
TI  - Consultation-based academic interventions for children with ADHD: effects on
      reading and mathematics achievement.
AB  - The purpose of this investigation was to evaluate the relative efficacy of two
      consultation-based models for designing academic interventions to enhance the
      educational functioning of children with attention-deficit/hyperactivity disorder
      (ADHD). Children (N=167) meeting DSM-IV criteria for ADHD were randomly assigned
      to one of two consultation groups: Individualized Academic Intervention (IAI;
      interventions designed using a data-based decision-making model that involved
      ongoing feedback to teachers) and Generic Academic Intervention (GAI;
      interventions designed based on consultant-teacher collaboration, representing
      "consultation as usual"). Teachers implemented academic interventions over 15
      months. Academic outcomes (e.g., standardized achievement test, and teacher
      ratings of academic skills) were assessed on four occasions (baseline, 3 months,
      12 months, 15 months). Hierarchical linear modeling analyses indicated
      significant positive growth for 8 of the 14 dependent variables; however,
      trajectories did not differ significantly across consultation groups.
      Interventions in the IAI group were delivered with significantly greater
      integrity; however, groups did not differ with respect to teacher ratings of
      treatment acceptability. The results of this study provide partial support for
      the effectiveness of consultation-based academic interventions in enhancing
      educational functioning in children with ADHD; however, the relative advantages
      of an individualized model over "consultation as usual" have yet to be
      established.

PMID- 17029026
TI  - Attention processes in children with movement difficulties, reading difficulties
      or both.
AB  - Reading difficulties (RD) and movement difficulties (MD) co-occur more often in
      clinical populations than expected for independent disorders. In this study, we
      investigated the pattern of association between attentional processes, RD and MD
      in a population of 9 year old school children. Children were screened to identify
      index groups with RD, MD or both, plus a control group. These groups were then
      tested on a battery of cognitive attention assessments (TEA-Ch). Results
      confirmed that the occurrence of RD and MD was greater than would be predicted
      for independent disorders. Additionally, children with MD, whether or not
      combined with RD, had poor performance on all attention measures when compared
      with typically developing children. Children with RD only, were no poorer on
      measures of attention than typical children. The results are discussed with
      respect to approaches proposed to account for the co-occurrence of disorders.

PMID- 17029028
TI  - Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic
      cells: friends or enemies?
AB  - The tumor microenvironment consists of a variable combination of tumor cells,
      stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as
      macrophages, T lymphocytes, and dendritic cells. A variety of cytokines,
      chemokines and growth factors are produced in the local tumor environment by
      different cells accounting for a complex cell interaction and regulation of
      differentiation, activation, function and survival of multiple cell types. The
      interaction between cytokines, chemokines, growth factors and their receptors
      forms a comprehensive network at the tumor site, which is primary responsible for
      overall tumor progression and spreading or induction of antitumor immune
      responses and tumor rejection. Although the general thought is that dendritic
      cells are among the first cells migrating to the tumor site and recognizing tumor
      cells for the induction of specific antitumor immunity, the clinical relevance of
      dendritic cells at the site of the tumor remains a matter of debate regarding
      their role in the generation of successful antitumor immune responses in human
      cancers. While several lines of evidence suggest that intratumoral dendritic
      cells play an important role in antitumor immune responses, understanding the
      mechanisms of dendritic cell/tumor cell interaction and modulation of activity
      and function of different dendritic cell subtypes at the tumor site is
      incomplete. This review is limited to discussing the role of intratumoral
      cytokine network in the understanding immunobiology of tumor-associated dendritic
      cells, which seems to possess different regulatory functions at the tumor site.

PMID- 17029029
TI  - Advances in methods for assessing tumor hypoxia in vivo: implications for
      treatment planning.
AB  - Tumor hypoxia and its downstream effects have remained of considerable interest
      for decades due to its negative impact on response to various cancer therapies
      and promotion of metastasis. Diagnosing hypoxia non-invasively can provide a
      significant advancement in cancer treatment and is the dire necessity for
      implementing specific targeted therapies now emerging to treat different aspects
      of cancer. A variety of techniques are being proposed to do so. However, none of
      them has yet been established in the clinical arena. This review summarizes the
      methods currently available to assess tumor hypoxia in vivo and their respective
      advantages and shortcomings. It also points out the impedances that need to be
      overcome to establish any particular method in the clinic, along with a broad
      overview of requirements for further advancement in this sphere of cancer
      research.

PMID- 17029030
TI  - The paradox of pro-inflammatory cytokines in cancer.
AB  - Cytokines such as IL-1 and TNF are primarily pro-inflammatory. The inflammation
      induced by these cytokines is reflected in the type of genes they induce. In the
      pathogenesis of carcinogenesis as well as tumor growth and spread, cytokines such
      as IL-1 and TNF induce chemokines that attract neutrophils. Neutrophils are key
      players in the production of reactive oxygen species and carcinogenesis. Another
      aspect of pro-inflammatory cytokines is the induction of adhesion molecules and
      metalloproteinases, both of which provide mechanisms for tumor invasion. Blocking
      cytokines, however, will reduce tumor growth and spread if administered at
      sufficient concentrations and will require parenteral therapy. However, blocking
      cytokines will not kill tumor cells nor prevent carcinogenesis. Blocking
      cytokines is best as an adjunct therapy together with tumorocidal drugs.

PMID- 17029031
TI  - Dynamics of increased neutrophil adhesion to ICAM-1 after contacting immobilized
      IL-8.
AB  - Changing affinity of beta(2)-integrins on neutrophils for their ligands on
      endothelium is a critical, regulated step in the inflammatory response. In this
      report, the dynamics of the neutrophil response to the inflammatory chemokine
      interleukin-8 (IL-8) is examined. Human IL-8 was immobilized on beads and brought
      into contact with neutrophils selected from whole blood samples. Resulting
      changes in cellular adhesion were assessed by measuring the adhesion frequency
      between a human neutrophil and a bead coated with the endothelial ligand ICAM-1
      (intercellular adhesion molecule-1). Cells engulfed the IL-8 coated beads within
      a few tens of seconds, and most of the cells exhibited an increase in adhesion to
      ICAM-1 after approximately 5 to 10 min of contact with IL-8 at room temperature
      (3 to 5 min at 37 degrees C). Neither monocyte chemotactic protein-1 (MCP-1) nor
      anti-CD45-coated beads caused any changes in adhesion to ICAM-1. IL-8 induced
      adhesion was blocked by antibody against CD18. At lower surface density of
      chemokine, approximately 20% of IL-8 coated beads adhered but were not engulfed
      by the cells, although the increase in adhesion for ICAM-1 was still effected.
      Heterogeneity in the cellular response and variability between donors was also
      noted.

PMID- 17029032
TI  - Knee-loading modality drives molecular transport in mouse femur.
AB  - Mechanical loading is well known to stimulate bone remodeling. Load-driven
      interstitial fluid flow and molecular transport have been postulated to play a
      role in the enhancement of bone formation. In order to evaluate load-driven
      molecular transport in a lacunocanalicular network, we conducted fluorescence
      recovery after photobleaching (FRAP) experiments using lacunae stained with
      uranine (376 Da). Loads were applied to a mouse femur ex vivo with a novel knee
      loading modality, where the distal epiphysis was loaded with a sinusoidal force
      at 2 Hz. The lacunae in the diaphysis located 25% (approximately 4 mm) proximal
      to the loading site were photobleached and sequentially imaged, and a time
      constant for fluorescence recovery was determined both with and without knee
      loading. The time constant was estimated as the period to recover 63% of
      fluorescent intensity using a best-fit exponential curve. The results reveal that
      the applied loads shortened the time constant from 33 +/- 9 s with non-loading
      control to 25 +/- 11 s with knee loading (p = 0.0014). The strain in the
      measurement site was <100 microstain along the femoral midshaft, which was an
      order of magnitude smaller than the minimum effective strain threshold for bone
      remodeling. Taken together, the current study supports the notion that molecular
      transport in cortical bone is enhanced by the loads applied to the epiphysis
      without inducing significant in situ strain in the diaphysis.

PMID- 17029033
TI  - The brain computer interface using flash visual evoked potential and independent
      component analysis.
AB  - In this study flashing stimuli, such as digits or letters, are displayed on a LCD
      screen to induce flash visual evoked potentials (FVEPs). The aim of the proposed
      interface is to generate desired strings while one stares at target stimulus one
      after one. To effectively extract visually-induced neural activities with
      superior signal-to-noise ratio, independent component analysis (ICA) is employed
      to decompose the measured EEG and task-related components are subsequently
      selected for data reconstruction. In addition, all the flickering sequences are
      designed to be mutually independent in order to remove the contamination induced
      by surrounding non-target stimuli from the ICA-recovered signals. Since FVEPs are
      time-locked and phase-locked to flash onsets of gazed stimulus, segmented epochs
      from ICA-recovered signals based on flash onsets of gazed stimulus will be
      sharpen after averaging whereas those based on flash onsets of non-gazed stimuli
      will be suppressed after averaging. The stimulus inducing the largest averaged
      FVEPs is identified as the gazed target and corresponding digit or letter is sent
      out. Five subjects were asked to gaze at each stimulus. The mean detection
      accuracy resulted from averaging 15 epochs was 99.7%. Another experiment was to
      generate a specified string '0287513694E'. The mean accuracy and information
      transfer rates were 83% and 23.06 bits/min, respectively.

PMID- 17029034
TI  - The role of pulse pressure in the hemodynamic control of hypertension: exploring
      the link to cardiovascular remodeling.
AB  - OBJECTIVE: To correlate the values in the basic blood pressure groups presented
      in the JNC 7th with the computed values of the Noninvasive Hemodynamic Analyzer
      (NHA) and to demonstrate the pathophysiological alterations by three proportional
      hypertensive models. DESIGN: Hemodynamic values of each of the blood pressure
      groups presented in the JNC 7th are tabulated for men between 20 and 50 years of
      age with particular interest in Pulse Pressure. PATIENTS: Idealized patients were
      used in the three groups of the proportional hypertensive models. VALIDITY:
      Previous studies demonstrated that the Bias, Precision, and Accuracy of Cardiac
      Output measurement, compared to Thermodilution technique, resulted in
      statistically acceptable clinical values. CONCLUSION: This research has
      successfully demonstrated, with the use of the NHA, the leading role of Pulse
      Pressure in normal and hypertensive patients. We are convinced that this
      technique can be used as an economical and time-saving alternative screening tool
      in clinical medicine.

PMID- 17029040
TI  - The epigenetic alteration of synovial cell gene expression in rheumatoid
      arthritis and the roles of nuclear factor kappaB and Notch signaling pathways.
AB  - Rheumatoid arthritis (RA) is a complex process of chronic and progressive
      inflammation associated with activation of numerous signaling molecules and
      transcription factors and hyperproliferation of synoviocytes of the affected
      joints, although the greater part of its pathophysiological process is explained
      by activation of nuclear factor kappaB (NF-kappaB). For example, the self
      perpetuating nature of the rheumatoid inflammation is ascribable to
      overexpression of the proinflammatory cytokines tumor necrosis factor alpha and
      interleukin-1beta, known to elicit the activation cascade for NF-kappaB and
      activator protein-1 that are responsible for transcriptional induction of these
      cytokines among other target genes, which conform a positive feedback loop for
      continuation and expansion of the inflammatory responses. In addition,
      comparative gene expression profile analyses have revealed activation of a number
      of genes that explain the "transformed-like" phenotype of synoviocytes. Among the
      genes expressed in rheumatoid synoviocytes upon inflammatory stimuli, induction
      of gene expression of Notch proteins and its ligand have been found. Possible
      roles of Notch signaling in RA synoviocytes are discussed.

PMID- 17029041
TI  - Naturopathic management of rheumatoid arthritis.
AB  - Complementary and alternative medicines (CAM) are widely used by those with pain
      and/or musculoskeletal problems, and previous research has shown that high
      proportions of individuals with rheumatoid arthritis have used these therapies.
      One of the largest CAM modalities is that of naturopathy, which combines
      nutritional, herbal, and other complementary practices to treat such conditions.
      In this review, evidence is examined in relation to those factors which
      naturopaths believe are significant contributors to rheumatoid arthritis, and are
      hence the main focus of therapeutic management. These factors include food
      allergy, increased gut permeability, increased circulating immune complexes,
      excessive inflammatory processes, and increased oxidative stress. Naturopathic
      treatment attempts to alleviate symptoms by altering these factors through
      dietary modification, manipulation of dietary fats, and use of antioxidants and
      proteolytic enzymes. An understanding of the rationale for these treatments and
      evaluation of the evidence from their use in clinical settings will assist with
      the integration of complementary and conventional practices in the treatment of
      rheumatoid arthritis.

PMID- 17029042
TI  - Prediction of and prophylaxis against Pneumocystis pneumonia in patients with
      connective tissue diseases undergoing medium- or high-dose corticosteroid
      therapy.
AB  - We performed a retrospective analysis to establish a statistical model for the
      prediction of Pneumocystis pneumonia (PCP) in patients with connective tissue
      diseases (CTD) undergoing medium- or high-dose corticosteroid therapy, to
      identify independent risk factors for PCP and to evaluate the efficacy of the
      prophylactic use of trimethoprim-sulfamethoxazole (TMP/SMX) against PCP. One
      hundred and twenty-four patients who were receiving the equivalent of or more
      than 30 mg/day of prednisol-one (PSL) were classified into two groups according
      to the presence (prophylaxis group, n = 46) or absence (nonprophylaxis group, n =
      78) of prophylactic TMP/SMX. We developed a statistical model that was suitable
      for predicting the development of PCP using a logistic regression analysis. The
      initial steroid dosage, decreased peripheral blood lymphocyte counts at 2 weeks
      (<500/microl), and usage of immunosuppressant during 2 weeks after the
      institution of PSL (>or=30 mg/day) were found to independently contribute to the
      development of PCP. Finally, in the patient group with a defined risk for PCP, a
      significant prophylactic effect of TMP/SMX was demonstrated. We recommend the
      prophylactic use of TMP/SMX for patients with CTD undergoing medium- or high-dose
      corticosteroid therapy who are determined to have a high risk of developing PCP.

PMID- 17029043
TI  - Infliximab acts directly on human osteoclast precursors and enhances osteoclast
      formation induced by receptor activator of nuclear factor kappaB ligand in vitro.
AB  - Infliximab is known to protect against the development of joint destruction. In
      the present study, we sought to determine whether Infliximab acts directly on
      human osteoclast precursors and influences monocyte-osteoclast differentiation
      induced by receptor activator of nuclear factor kappaB ligand (RANKL) in vitro.
      Peripheral blood mononuclear cells (PBMCs) isolated from rheumatoid arthritis
      (RA) patients and normal controls were cultured in the presence of RANKL and
      macrophage colony stimulating factor. Infliximab, antihuman tumor necrosis factor
      alpha (TNFalpha), antihuman TNF soluble receptor p55 (TNFR p55), and antihuman
      TNF soluble receptor p75 (TNFR p75) antibodies were added. Osteoclast formation
      was determined by assessing the number of tartrate-resistant acid phosphatase
      (TRAP) staining cells and the extent of lacunar resorption. Addition of
      Infliximab resulted in a marked increase in the number of TRAP-positive
      multinucleated cells (TRAP(+) MNCs) and in the extent of lacunar resorption
      compared with the control cultures. Antihuman TNFalpha antibody showed the same
      effect; however, the addition of neither TNFR p55 nor TNFR p75 antibody affected
      the extent of TRAP(+) MNCs and lacunar resorption. Our results suggest that
      infliximab acts directly on early osteoclast precursors, and stimulates
      osteoclast formation and lacunar resorption induced by RANKL in vitro.

PMID- 17029036
TI  - Gender-dependent modulation of brain monoamines and anxiety-like behaviors in
      mice with genetic serotonin transporter and BDNF deficiencies.
AB  - 1. Brain-derived neurotrophic factor (BDNF) supports serotonergic neuronal
      development and our recent study found that heterozygous mice lacking one BDNF
      gene allele interbred with male serotonin transporter (SERT) knockout mice had
      greater reductions in brain tissue serotonin concentrations, greater increases in
      anxiety-like behaviors and greater ACTH responses to stress than found in the
      SERT knockout mice alone. 2. We investigated here whether there might be gender
      differences in these consequences of combined SERT and BDNF deficiencies by
      extending the original studies to female mice, and also to an examination of the
      effects of ovariectomy and tamoxifen in these female mice, and of 21-day 17-beta
      estradiol implantation to male mice. 3. We found that unlike the male SERTxBDNF
      deficient mice, female SERTxBDNF mice appeared protected by their gender in
      having significantly lesser reductions in serotonin concentrations in
      hypothalamus and other brain regions than males, relative to controls. Likewise,
      in the elevated plus maze, female SERTxBDNF-deficient mice demonstrated no
      increases in the anxiety-like behaviors previously found in males. 4.
      Furthermore, female SERTxBDNF mice did not manifest the approximately 40%
      reduction in the expression of TrkB receptors or the approximately 30% reductions
      in dopamine and its metabolites that male SERTxBDNF did. After estradiol
      implantation in male SERTxBDNF mice, hypothalamic serotonin was significantly
      increased compared to vehicle-implanted mice. These findings support the
      hypothesis that estrogen may enhance BDNF function via its TrkB receptor, leading
      to alterations in the serotonin circuits, which modulate anxiety-like behaviors.
      5. This double-mutant mouse model contributes to the knowledge base that will
      help in understanding genexgenexgender interactions in studies of SERT and BDNF
      gene polymorphisms in human genetic diseases such as anxiety disorders and
      depression.

PMID- 17029044
TI  - Malnutrition and disease progression in patients with rheumatoid arthritis.
AB  - To examine the changes in nutritional status during the progression of rheumatoid
      arthritis (RA), we studied anthropometric and biochemical variables in 97
      Japanese patients with RA. Anthropometric data included body mass index (BMI),
      triceps skinfold thickness (TSF), and arm muscle area (AMA). Levels of albumin
      and cholesterol in serum, and lymphocyte count were studied as biochemical
      variables. The prevalence of malnutrition defined as hypoalbuminemia less than
      3.4 g/dl was 24.7%, similar to the reports in other countries. Analysis of the
      data according to disease stage showed that malnutrition in RA was characterized
      by a progressive reduction in body protein. Body mass index and TSF were
      increased in patients with stage 1 disease, whereas serum albumin and AMA were
      within normal range. Stage 2 patients had normal BMI with decreased body protein,
      albumin, and AMA. Progression to stages 3 and 4 was associated with a stepwise
      decrease in AMA; serum albumin and BMI remained in the same range as stage 2.
      Albumin values and AMA were significantly lower in patients with poor functional
      class and high C-reactive protein. The characteristic progression of malnutrition
      in RA is attributed to excessive protein catabolism evoked by inflammatory
      cytokines and by disuse atrophy due to functional impairment.

PMID- 17029045
TI  - Transforming growth factor beta stimulates rheumatoid synovial fibroblasts via
      the type II receptor.
AB  - Transforming growth factor (TGF)-beta regulates the function of fibroblasts, and
      has been shown to have a role in the pathogenesis of rheumatoid arthritis (RA)
      because several studies have demonstrated the presence of TGF-beta in the
      synovial tissue and synovial fluids of RA patients. In this study, we examined
      the expression of TGF-beta receptors in synovial fibroblasts of patients with RA
      and demonstrated the significance in functional responses of synovial fibroblasts
      to TGF-beta in this disorder. Transforming growth factor beta1 stimulated the
      expression of connective tissue growth factor (CTGF) in fibroblasts of patients
      with RA more than in those of patients with osteoarthritis (OA). Transforming
      growth factor beta1 induced the chemotactic migration of RA synovial fibroblasts
      and inhibited their proliferation significantly more than OA synovial
      fibroblasts. Both RA and OA synovial fibroblasts expressed detectable amounts of
      TGF-beta receptor type II mRNA, but the expression was higher in RA patients than
      in OA patients, as assessed by reverse transcriptase-polymerase chain reaction.
      There was no significant difference in the expression of TGF-beta receptor type I
      or type III in synovial fibroblasts between RA and OA patients. These results
      indicate that synovial fibroblasts of RA patients express the increased TGF-beta
      receptor type II, which is associated with altered responses to TGF-beta observed
      in CTGF expression, chemotaxis, and proliferation of RA synovial fibroblasts, and
      may have an important role in the pathogenesis of RA.

PMID- 17029046
TI  - A case of nodular-type muscular sarcoidosis: findings of imaging, histopathology,
      and polymerase chain reaction.
AB  - We report a case of nodular-type muscular sarcoidosis with no systemic symptoms.
      Thallium-201 scintigraphy showed intense uptake in the muscular lesion mimicking
      malignant soft tissue tumor. Magnetic resonance imaging (MRI) demonstrated
      characteristic signal patterns of peripheral high intensity with central low
      intensity ("three stripes" pattern). Microscopy revealed sarcoid granuloma with
      typical histopathological characteristics. Propionibacterium acnes was detected
      on polymerase chain reaction analysis of the excised tissue.

PMID- 17029047
TI  - Rheumatoid arthritis complicated with myeloperoxidase antineutrophil cytoplasmic
      antibody (MPO-ANCA)-associated vasculitis: a case report.
AB  - This article describes a patient with rheumatoid arthritis (RA) with crescentic
      glomerulonephritis (CrGN) associated with myeloperoxidase-antineutrophil
      cytoplasmic antibodies (MPO-ANCA), who responded well to methotrexate (MTX). A 48
      year-old woman with a 4-year history of RA was admitted with fever and elevated C
      reactive protein. On laboratory evaluation, her level of MPO-ANCA was 422 EU, and
      urinalysis revealed proteinuria and hematuria. Because she was also suffering
      from episcleritis, vasculitis was considered. A renal biopsy was performed, which
      revealed necrotizing CrGN. We diagnosed RA complicated with MPO-ANCA-associated
      vasculitis. We considered treatment with high-dose oral prednisolone for
      vasculitis, but the patient refused this treatment. We started MTX at a dose of 8
      mg/week for RA from the time of admission, and the patient responded immediately.
      Biochemical parameters, including C-reactive protein, erythrocyte sedimentation
      rate, rheumatoid factor, and MPO-ANCA, improved. Seven months later, MPO-ANCA had
      decreased to 46 EU. In clinical studies, few patients have been reported with RA
      complicated with ANCA-associated CrGN. This case differs from previous cases in
      the treatment given. No high-dose steroid with intensive immunosuppression or
      plasma exchange was required.

PMID- 17029048
TI  - Repeated postoperative laryngeal obstruction due to bilateral cricoarytenoid
      joint involvement in rheumatoid arthritis.
AB  - A 61-year-old woman with a 40-year history of severe rheumatoid arthritis
      developed postoperative laryngeal obstruction twice; the first episode occurred
      just after surgery for cervical myelopathy and the second episode occurred 3
      weeks after surgery when physiotherapy activity increased. A flexible laryngeal
      endoscopy demonstrated that abduction of the bilateral vocal cords was severely
      disturbed at the paramedian position, suggesting a diagnosis of cricoarytenoid
      arthritis. Early administration of corticosteroids was successful.

PMID- 17029049
TI  - Concurrent occurrence of allergic granulomatous angiitis and temporal arteritis:
      a case report and review of the literature.
AB  - Allergic granulomatous angiitis (AGA) is a disease entity that was first
      distinguished from classical polyarteritis nodosa by Churg and Strauss in 1951,
      and is characterized by the clinical features of allergic rhinitis or bronchial
      asthma, eosinophilia, and vasculitis. Allergic granulomatous angiitis has been
      described to mainly involve small vessels. We herein describe a case of Churg
      Strauss syndrome which demonstrated the clinical and laboratory findings
      supporting a diagnosis of AGA and was also associated with the clinical and
      pathological findings for temporal arteritis, which was characterized by
      eosinophil infiltration and granuloma formation of the temporal artery (middle
      sized vessel).

PMID- 17029050
TI  - Catastrophic transverse myelitis in a patient with systemic lupus erythematosus.
AB  - A 24-year-old Japanese woman was admitted to our hospital suffering from high
      fever and progressive paralysis in both legs. Magnetic resonance imaging of the
      spinal cord showed high-intensity signals from C5 to Th4 and from Th7 to L1 on T2
      weighted images. The patient was diagnosed as having acute transverse myelitis
      trade mark, which was a complication of systemic lupus erythematosus based on the
      serological findings. Despite aggressive immunosuppressive treatments including
      corticosteroid pulse therapy, plasmapheresis, and intravenous cyclophosphamide,
      the paralysis of her lower extremities did not improve. In the catastrophic type
      of lupus-associated TM, which develops extensively and longitudinally along the
      spinal cord, the prognosis still seems to be poor despite intensive treatments.

PMID- 17029051
TI  - Normotensive scleroderma renal crisis with diffuse alveolar damage after
      corticosteroid therapy.
AB  - A 68-year-old woman with systemic sclerosis developed acute respiratory failure
      due to diffuse alveolar hemorrhage and normotensive scleroderma renal crisis
      (SRC) shortly after the initiation of corticosteroid therapy. Treatment with
      angiotensin-converting enzyme inhibitor and plasmapheresis had failed in this
      patient. Autopsy showed diffuse alveolar damage and thrombotic micro-angiopathy.
      The sequence of events in this patient clarifies the pathologic process of
      normotensive SRC, and suggests a causative role of corticosteroid therapy and
      normotensive SRC.

PMID- 17029052
TI  - Bilateral total knee arthroplasty after spontaneous osseous ankylosis in
      rheumatoid arthritis.
AB  - Total knee arthroplasty (TKA) was carried out on both knee joints for spontaneous
      bony ankylosis due to rheumatoid arthritis (RA). Preoperative fixation angles
      were 40 degrees . First, the peroneal nerve was released prior to TKA. Quadriceps
      snip was performed to evert the patella laterally. Bilateral TKAs were carried
      out using a stabilized prosthesis. The results showed full extension to 70
      degrees flexion at 3 years after the surgery. Absence of pain, maintenance of
      stability, and walking ability were achieved, without any significant
      complication. Total knee arthroplasty following takedown of a spontaneous
      ankylosed knee is an effective procedure under appropriate knee conditions.

PMID- 17029053
TI  - Sensorimotor polyneuropathy as an initial clinical manifestation of sarcoidosis.
AB  - A 45 year-old Japanese woman developed numbness and tingling of both hands and
      feet. Electrophysiological examination revealed sensorimotor polyneuropathy. She
      was diagnosed as suffering from sarcoidosis on the basis of the pathological
      findings from dermal biopsy. Steroid therapy effectively improved the clinical
      symptoms. Although sarcoid neuropathy is rare, this case suggests sensorimotor
      polyneuropathy is an important symptom of sarcoidosis and can represent the
      initial clinical manifestation of the disease.

PMID- 17029054
TI  - Bronchiolar disease associated with gold compounds administration in a patient
      with rheumatoid arthritis.
AB  - We report the case of a female patient with rheumatoid arthritis (RA) treated
      with gold sodium thiomalate and auranofin who developed bronchopulmonary
      involvement. Chest X-ray films showed diffuse mottled infiltrates and bronchial
      wall thickness in both lungs. Computed tomography revealed opacities along the
      thickening of the bronchovascular bundles. The pathologic findings were
      indistinguishable from those of diffuse panbronchiolitis. After discontinuation
      of gold compounds and initiation of steroid administration, her subjective
      symptoms immediately subsided. We conclude that our patient, who had suffered
      from chronic sinusitis and had a predisposition to bronchiolar disease, had
      bronchiolar disease induced by gold compounds.

PMID- 17029055
TI  - Treatment of early rheumatoid arthritis.
AB  - Recent advances in the understanding of the pathophysiology, aggressive
      treatment, and early detection of rheumatoid arthritis (RA) have changed the
      clinical, pathologic, and functional outcomes in patients with RA. Early
      aggressive treatment of RA has now become the norm in clinical practice rather
      than the use of the traditional pyramid approach of the last half of the
      twentieth century. Early treatment with monotherapy of traditional disease
      modifying antirheumatic drugs (DMARDs) or biologics, combination traditional
      DMARD therapy and, especially, combination of biologic therapy and methotrexate,
      have revolutionized the treatment of RA, producing significant improvement in
      clinical, radiographic, and functional outcomes not seen previously. For the
      individual patient, we still cannot determine which medication or combination of
      medications will give the most complete response. There have been a number of
      recent, well-designed clinical trials that have tried to answer this question.
      Herein we review the evidence-based medicine that addresses these issues.

PMID- 17029056
TI  - Glucocorticoid-induced osteoporosis: skeletal manifestations of glucocorticoid
      use and 2004 Japanese Society for Bone and Mineral Research-proposed guidelines
      for its management.
AB  - Glucocorticoid (GC) is widely used to treat a variety of inflammatory and
      allergic diseases, and about 0.9% of the adult population in Japan (approximately
      one million people) are known to take oral GC at any given time. GC causes a
      number of significant side effects, among which are skeletal manifestations such
      as osteoporosis and degenerative bone fracture, maor complications of GC therapy.
      Although the population of GC-induced osteoporosis patients is estimated to be
      approximately one-fifth of patients with primary osteoporosis, few physicians are
      aware of the increased risk of fracture caused of GC, and there is inadequate
      information concerning the effetiveness of prevention and treatment of GC-induced
      osteoporosis. Recently, mechanisms of GC-induced osteoporosis have been
      clarified, and treatment strategies have been developed. Accordingly, the 2004
      Japanese Society for Bone and Mineral Research (JSBMR)-proposed guidelines for
      the management and treatment of GC-induced osteoporosis have been developed based
      on the results of a longitudinal study by subcommittee members and the results of
      an analysis of patients collected by the Subcommittee to Study Diagnostic
      Criteria for Corticosteroid-induced Osteoporosis, together with evidence obtained
      overseas and in Japan. The present guideline is prepared for clinical practice.

PMID- 17029057
TI  - Locking compression plating: a new solution for fractures in rheumatoid patients.
AB  - Osteoporosis is a well-known phenomenon in rheumatoid arthritis (RA) that is
      characterized by marked loss of peripheral bone. It was found that the frequency
      of osteoporosis in RA can be increased significantly compared with the reference
      population, which implies a higher risk of fracture in this group of patients.
      Osteoporosis makes the treatment of fracture in RA patients more challenging,
      including the difficulty of fracture fixation, delayed union, secondary loss of
      reduction, and fixation failure. The locking compression plate was designed using
      the concept of "internal fixator," which provides a new solution for the fixation
      of osteoporotic fractures. The fixed angle between the screw and the plate
      increases the pull-out strength of the system, so the stability of the fixation
      no longer depends totally on the quality of the bone. The other benefits of this
      system include the fact that no accurate contouring is required, it protects the
      local blood supply, and it supports minimally invasive plate osteosynthesis.

PMID- 17029058
TI  - Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging
      features.
AB  - Imaging findings of 26 cases of leflunomide (Arava)-related acute lung injury
      were analyzed. Thirteen cases had pre-existing interstitial pulmonary disease on
      chest X-ray or computed tomography. The main features of clinically determined
      leflunomide-induced acute lung injury were similar to those caused by other
      drugs: diffuse or widespread patchy ground-glass opacities and/or consolidation,
      frequently accompanied by septal thickening and intralobular reticular opacities.
      We categorized these findings into four patterns: diffuse alveolar damage (DAD),
      acute eosinophilic pneumonia, hyperreaction, and cryptogenic organizing
      pneumonia. The DAD group had a higher mortality rate, but statistically not a
      significant one. It is impossible to exclude infectious disease such as
      pneumocystis carinii pneumonia based on imaging findings, and detailed
      correlation of imaging findings with clinical and laboratory findings is
      essential in order to make a correct diagnosis.

PMID- 17029060
TI  - Radiographic comparative evaluation of the Sauve-Kapandji procedure and the
      Darrach procedure for rheumatoid wrist reconstruction.
AB  - For surgical treatment of rheumatoid wrists, we have routinely selected the Sauve
      Kapandji (S-K) procedure or the Darrach procedure based on predetermined
      indications. In this study, we conducted a retrospective radiographic comparative
      evaluation of the changes in the carpus after the two procedures. The S-K group
      and the Darrach group each consisted of 13 wrists of 10 patients (all women). The
      indications for the Darrach procedure were the presence of radiolunate fusion,
      radial shelf formation, and old age. The carpal height ratio (CHR) and the
      ulnocarpal distance ratio (UCDR) were determined on wrist radiograms obtained
      before operation and at the final follow-up. The mean follow-up period was 4
      years. Fisher's test was used to analyze the differences between the two groups.
      Both groups showed a decrease in mean CHR and an increase in mean UCDR at the
      final follow-up compared to the values before the operation, and there were no
      statistically significant differences. Furthermore, in the Darrach group, no
      significant differences in changes of the carpus were observed between patients
      with or without a radial shelf. We concluded that the present results do not
      support the superiority of the S-K method over the Darrach procedure for
      rheumatoid wrist reconstruction based on a radiographic evaluation.

PMID- 17029059
TI  - Analysis for the major contributor of collagenase to the primary cleavage of type
      II collagens in cartilage degradation.
AB  - Degradation of type II collagen is a central process in cartilage destruction
      seen in osteoarthritis and rheumatoid arthritis. Primary cleavage of type II
      collagen at the collagenase site is rate-limiting and is, therefore, a critical
      step for its degradation. The major contributor to this cleavage was identified
      in three isozymes of collagenase in human cartilage. Primary cultured human
      chondrocytes were used for the study. The production of collagenase-1 was major
      in total production for three isozymes of collagenase after stimulations with any
      concentration of tumor necrosis factor-alpha and/or interleukin-1 at 48 and 72 h,
      comprising 98% or greater of the total collagenase. When the production of
      collagenase-1 was specifically suppressed by the transfection with duplexes of 21
      nucleotide small interfering ribonucleic acid into the cells, the activity of
      type II collagen cleavage was linearly decreased at neutral pH after activation.
      The relative contribution of collagenase-1 to the primary cleavage of type II
      collagen was determined to be 85%-93%. These findings suggest that collagenase-1
      is a major contributor to the primary cleavage of type II collagens in human
      cartilage and is a potential therapeutic target for osteoarthritis and rheumatoid
      arthritis.

PMID- 17029061
TI  - Clinical characteristics of Pneumocystis carinii pneumonia in patients with
      connective tissue diseases.
AB  - The characteristics of Pneumocystis carinii pneumonia (PCP) in patients with
      connective tissue diseases (CTDs) were examined retrospectively. Nine patients
      were enrolled in this study. Their mean age was 57.1 years. All the patients
      received a high-dose steroid or immunosuppressant. The onset (mean 6.6 days) of
      fever, cough, breathlessness, and geographical ground-glass opacities revealed by
      chest computed tomography was acute. The serum beta-D: -glucan level increased
      with a simultaneous increase in the Krebs von den Lungen (KL)-6 or surfactant
      protein D level. The serum immunoglobulin G (IgG) and albumin levels and the
      peripheral blood lymphocyte count at the onset of PCP were low, but only the
      serum IgG level decreased significantly. The patients were treated with
      trimethoprim-sulfamethoxazole or pentamidine isetionate. Six patients died
      eventually: two patients of progressive respiratory failure, two probably due to
      a recurrence of the PCP, and two with microbial respiratory infections other than
      PCP. Five of the six patients required mechanical ventilation. Three patients
      received secondary prophylaxis and survived. In conclusion, the acute onset was
      characteristic of PCP in patients with CTDs. High-dose steroids,
      immunosuppressants, and hypogammaglobulinemia are risk factors; and respiratory
      failure requiring mechanical ventilation, severe secondary infections, and a lack
      of secondary prophylaxis are poor prognostic factors. Secondary prophylaxis is
      recommended for all of these patients.

PMID- 17029062
TI  - Progressive facial hemiatrophy complicated by sclerodactyly, Raynaud's
      phenomenon, anti-ribonucleoprotein antibody, and trigeminal nerve disturbance.
AB  - A Japanese woman was diagnosed as having progressive facial hemiatrophy when she
      was 26 years old. After 30 years, Raynaud's phenomenon and sclerodactyly suddenly
      appeared; at the same time, positive rheumatoid factor and anti-ribonucleoprotein
      (anti-RNP) antibody were noted on serological examinations. When she was 60 years
      old, trigeminal nerve disturbance also appeared. The associations between
      progressive facial hemiatrophy, systemic scleroderma, and trigeminal nerve
      disturbance are interesting and should be discussed.

PMID- 17029063
TI  - Anaphylactic reaction to infliximab in two rheumatoid arthritis patients who had
      previously received infliximab and resumed.
AB  - Here we report on two cases of anaphylactic reaction following infliximab
      infusion in patients with active rheumatoid arthritis (RA). Both individuals had
      received infliximab treatment during a clinical trial approximately 2 years prior
      to further therapy; subsequent infusion of this agent led to anaphylactic
      reactions in both cases. In light of these findings, we recommend that future
      treatments with infliximab in RA patients who have previously received this agent
      should be carefully monitored.

PMID- 17029064
TI  - A case of Vogt-Koyanagi-Harada disease that developed relapsing polychondritis.
AB  - We report the case of a 56-year-old Japanese man with Vogt-Koyanagi-Harada
      disease in whom pain and diffuse swelling of the left auricle and bilateral
      episcleritis developed 3 years after diagnosis. Biopsy of the left ear showed
      acute chondritis, leading to another diagnosis of relapsing polychondritis.
      Additionally, he was found to carry human leukocyte antigen DR4, which has been
      reported to be associated with these inflammatory conditions. To our knowledge,
      our patient is the first reported case of the occurrence of relapsing
      polychondritis and Vogt-Koyanagi-Harada disease.

PMID- 17029065
TI  - A patient with symptomatic osteomalacia associated with Fanconi syndrome.
AB  - We report a patient with renal tubulointerstitial fibrosis and symptomatic
      osteomalacia associated with Fanconi syndrome. A 55-year-old woman was
      hospitalized because of an inability to walk. Beginning approximately 2 years
      previously, she had experienced gradually worsening pain in the hips, shoulders,
      and trunk, culminating in a bedridden state. Serum urea nitrogen was 38 mg/dl;
      creatinine, 2.6 mg/dl; uric acid. 3.6 mg/dl; phosphate, 2.3 mg/dl; and alkaline
      phosphatase, 2111 IU/l. Urinary beta2 microglobulin was 72 331 microg/day.
      Aminoaciduria, renal glucosuria, and proximal renal tubular acidosis with a
      normal anion gap were also noted. The patient was diagnosed with Fanconi
      syndrome. Radiography demonstrated typical Looser zones in the proximal portion
      of the left and especially the right femoral shaft, and at several other sites. A
      renal biopsy specimen disclosed severe tubulointerstitial fibrosis with little
      cellular infiltration. Glomeruli were largely intact. A bone biopsy specimen
      indicated osteomalacia; no tetracycline labeling could be seen along most
      trabecular bone surfaces, and the ratio of total osteoid volume to bone volume
      was increased (71.8%). Bicarbonate administration (9 g/day) gradually lessened
      most symptoms, permitting ambulation. Calcitriol administration decreased
      excessive intact-parathyroid hormone emerging after 2 months of acidosis
      correction. Thus, severe acidosis associated with Fanconi syndrome can induce
      osteomalacia showing serious skeletal complications, but also responsiveness to
      bicarbonate therapy.

PMID- 17029066
TI  - Two cases of cervical abscess in rheumatoid arthritis patients.
AB  - The prognosis of rheumatoid arthritis (RA) has recently been improved, resulting
      in longer survival of patients. The incidence of oral diseases increases with
      age, particularly for periodontal disease and those involving tooth decay, even
      in normal healthy individuals. Patients with RA display increased incidence of
      oral diseases, and the use of steroids or methotrexate to treat RA increases
      susceptibility to infections, sometimes causing serious infections. We present
      here two cases of cervical abscesses in RA patients who underwent emergency
      surgery to treat oral infections due to the possibility of mediastinal
      inflammation.

PMID- 17029067
TI  - Levofloxacin-induced Achilles tendon rupture in a patient with systemic
      microscopic polyangiitis.
AB  - We report a case of spontaneous Achilles tendon rupture associated with
      myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA)-related
      microscopic polyangiitis in a 77-year-old man who was treated with oral
      corticosteroids. Several days after 10 days of treatment with levoflaxacin (daily
      dose 200 mg) for bacterial pneumonia, he noted discomfort around both Achilles
      tendons. The discomfort developed into swelling around his left ankle, and he
      could not walk well. We diagnosed bilateral Achilles tendinitis with spontaneous
      rupture induced by levofloxacin. Epidemiological studies show that the risk of
      fluoroquinolone-related tendon rupture is highest among patients over the age of
      60 years who are receiving a corticosteroid. Rupture of the Achilles tendon is a
      rare but serious side effect of fluoroquinolone usage. Thus, physicians should be
      aware of this adverse effect, especially when prescribing medication for aged
      patients being treated with corticosteroids.

PMID- 17029068
TI  - A case of systemic lupus erythematosus: continued association of circulating
      prolactin levels with disease activity over a 4-year follow-up period.
AB  - Circulating prolactin levels in a woman with systemic lupus erythematosus (SLE)
      were measured over a period of 4 years, and her hyperprolactinemia remained
      associated with disease activity throughout. Circulating prolactin could thus be
      a better practical marker than standard parameters such as anti-double-stranded
      DNA antibodies and serum complement in some patients with SLE.

PMID- 17029069
TI  - A lupus-like butterfly rash following infliximab therapy.

PMID- 17029070
TI  - Osteoimmunological insight into bone damage in rheumatoid arthritis.
AB  - Research into the bone destruction associated with rheumatoid arthritis has
      highlighted the importance of the interplay of the immune and skeletal systems.
      Arthritic bone destruction is attributable to the defective control of
      osteoclastogenesis by T cells. We revealed that excessive expression of receptor
      activator of NF-kappaB ligand (RANKL) and a paucity of interferon-gamma underlie
      the enhanced osteoclastogenesis in arthritis. The interdisciplinary research
      field called osteoimmunology has attracted further attention after identification
      of a number of unexpected bone phenotypes in mice lacking immunomodulatory
      molecules. Accumulating evidence suggests that the immune and skeletal systems
      share not only cytokines but also various signaling molecules, transcription
      factors, and membrane receptors. Thus, bone turns out to be a dynamic tissue that
      is constantly renewed, where the immune system participates to a hitherto
      unexpected extent. This emerging field will be of great importance for a better
      understanding and treatment of rheumatic diseases.

PMID- 17029071
TI  - Mechanisms of bone loss in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune inflammatory disease in which
      destruction of bone in the joints causes major morbidity. Recent research has
      shed light on the cell and molecular mechanisms that lead to this osteolysis, all
      due directly or indirectly to the chronic inflammation. The aspects of this
      research covered in this review include the alteration of cell proliferation and
      survival that results in growth of the RA synovium. This process depends upon an
      increase in angiogenesis and local blood flow, which is also a feature of
      increased bone turnover. In addition, the inflammatory environment increases
      expression of chemokines, which are involved in the recruitment of monocytic
      osteoclast precursors. Chronic inflammation also promotes an overall catabolic
      state, with increased osteoclast differentiation and resorptive activity, driven
      by disregulation of receptor activator of NF-kappaB ligand (RANKL) and the
      synergistic activity of inflammatory cytokines such as tumor necrosis factor
      alpha and interleukin-1. Osteoclast survival is increased in this environment,
      but osteoblast differentiation and survival are decreased, with a consequent
      reduction in bone formation and a net loss of bone. Recognition of these
      processes and the factors involved will enable more effective and targeted
      treatments for RA.

PMID- 17029072
TI  - Long-term outcome of patients with rheumatoid arthritis treated by multiple
      arthroplasty.
AB  - We conducted a study of 82 patients with rheumatoid arthritis (RA) who had
      undergone multiple arthroplasty and investigated their clinical findings and
      clinical courses. We reviewed the significance of multiple arthroplasty in the
      treatment of RA, its problems, and measures to solve them. All patients initially
      regained and maintained good walking capacity. However, the walking capacity of
      many patients again decreased over the long term; in the tenth year, 79% of
      patients were capable of a practical gait. The causes of decreased walking
      capacity included complications of artificial joints, cervical lesions, and
      vertebral compression fractures. Fractures were observed in as many as nine
      patients, indicating that it is important to prevent and treat their cause, that
      is, osteoporosis. The survival rate was 71% in 10 years. In RA patients,
      particularly those who have undergone multiple arthroplasty, the major causes of
      death are infection and rheumatic disease, suggesting that prevention of such
      diseases should be considered paramount. Appropriate systemic treatment of RA,
      patient education, and measures against osteoporosis for prevention of
      complications may preserve the worth of multiple arthroplasty for RA patients
      with multiple joint destruction.

PMID- 17029073
TI  - Effect of G-1 column (Adacolumn) therapy in rats with adjuvant arthritis on the
      migration and immunoreactivity of peripheral and splenic leukocytes.
AB  - The G-1 column (Adacolumn), a novel extracorporeal adsorption device, is now
      available for the treatment of such chronic inflammatory diseases as ulcerative
      colitis and rheumatoid arthritis. G-1 column treatment sometimes results in a
      rapid decrease in clinical inflammatory parameters and/or has a delayed
      beneficial effect on disease activity. In order to identify the scientific basis
      for such clinical benefits, we studied rats with adjuvant arthritis induced by
      immunization with Mycobacterium butyricum antigen. The potential role of G-1
      column treatment on the migratory properties and immunoreactivities of leukocytes
      was investigated. Treatment of arthritic rats for 60 min with an extracorporeal
      perfusion through the G-1 column led to the adsorption of a small proportion
      (20%) of circulating granulocytes and monocytes. However, after G-1 treatment,
      the migration of radiolabeled blood granulocytes and monocytes to sites of acute
      dermal inflammatory reactions decreased significantly, in the case of
      granulocytes, almost by half. The migration of granulocytes to the inflamed
      hindpaws of severely affected animals was diminished in the G-1 treated group.
      Granulocytes that have passed through the G-1 column may stay in the bloodstream
      because of their markedly diminished number of adhesion molecules. A slightly
      increased accumulation in the liver and a decreased localization in the lung was
      also observed. These results may be relevant to the rapid clinical anti
      inflammatory effect observed in rheumatoid arthritis and possibly also in
      ulcerative colitis, without any pulmonary complications. In contrast, the
      adsorption rate by the G-1 column of T lymphocytes was very low, and their
      migration pattern to sites of dermal inflammatory reactions was not altered after
      treatment. However, the antigen (Mycobacterium purified protein derivative)
      reactivity of T lymphocytes in blood was almost completely abolished after G-1
      column treatment of arthritic rats. This unexpected qualitative effect on T
      lymphocytes of G-1 treatment warrants further detailed study.

PMID- 17029074
TI  - Clinical characteristics of anti-glucose-6-phosphate isomerase antibody-positive
      Japanese patients with rheumatoid arthritis.
AB  - Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are known to be
      arthritogenic in mice. These Abs are elevated in several forms of arthritic
      condition in humans, although their prevalence in rheumatoid arthritis (RA)
      patients is still in debate. Some RA patients have increased levels of anti-GPI
      Abs, but their clinical manifestation and relevance to other Abs are not clearly
      elucidated. The aims of this study were to explore the clinical and hematological
      characteristics of RA with anti-GPI Abs, and to compare their prevalence in RA
      patients, systemic lupus erythematosus (SLE) patients, and healthy subjects (HS)
      in a Japanese population. Anti-GPI Abs were positive in 16 patients with RA (12%,
      n = 137), in 10 patients with SLE (8%, n = 131), and in 6 HS (4%, n = 139). C
      reactive protein (CRP), immunoglobulin G, and the antinuclear antibody titer were
      higher in anti-GPI-positive patients than in those who were negative (P = 0.049,
      P = 0.0003, and P = 0.002, respectively). Moreover, the positivity of anti-GPI
      Abs was correlated with CRP more than with rheumatoid factor in RA patients. It
      is unclear whether anti-GPI Abs can predict the progress of disease, but the
      prevalence of these Abs was higher in active RA patients with severe arthritis,
      suggesting that anti-GPI Abs may be related to the pathogenesis of severe forms
      of arthritis.

PMID- 17029075
TI  - Inhibitory effect of mizoribine on matrix metalloproteinase-1 production in
      synovial fibroblasts and THP-1 macrophages.
AB  - To investigate the mechanism of antirheumatic action of mizoribine (MZR), we
      examined the expression of matrix metalloproteinase-1 (MMP-1) and MMP-3 utilizing
      THP-1 derived macrophage-like cells (THP-1 macrophages) and human synovial
      fibroblasts (SFs). The cells were respectively stimulated with lipopolysaccharide
      (LPS) and interleukin-1beta in the presence or absence of MZR in vitro. The
      concentrations of MMP-1 and MMP-3 in the supernatant were measured by enzyme
      linked immunosorbent assay. The secretion of MMP-1 from SFs, as well as THP-1
      macrophages, was inhibited by MZR in a dose-dependent manner. Furthermore, a
      quantitative real-time polymerase chain reaction revealed that MZR decreased the
      expression of MMP-1 messenger RNA. These findings may be an explanation for the
      clinical effect of MZR in patients with rheumatoid arthritis.

PMID- 17029076
TI  - Follow-up study of ankle arthrodesis in severe hind foot deformity in patients
      with rheumatoid arthritis using an intramedullary nail with fins.
AB  - We report herein a retrospective study of 25 cases of ankle arthrodesis performed
      in 23 patients with rheumatoid arthritis (RA) using an intramedullary nail with
      fins, developed in 1994. Surgical treatment, postoperative management, and
      clinical evaluation are described. Clinical evaluation, at an average follow-up
      period of 7 years 1 month, was based on foot disease scores from the Japanese
      Orthopedic Association; we compared these scores pre- and postoperatively, and
      during follow-up. These parameters showed a significant difference between
      preoperation and the follow-up period. However, instability only significantly
      improved when compared between pre- and postoperation. Arthrodesis using an
      intramedullary nail with fins was effective for the treatment of severe deformity
      of the hind foot. Nonunion was not observed and no remarkable changes of the
      Chopart joint were recognized between preoperation and the follow-up period. In
      our series, delayed wound healing was recognized in 6 of 25 joints. However,
      infection or neuropathy and other complications were not found. Arthrodesis using
      an intramedullary nail with fins is a viable treatment option for severe
      deformity of the hind foot in RA patients, because nonunion was not recognized
      and the clinical results over an average 7-year follow-up period were good or
      satisfactory.

PMID- 17029077
TI  - The relationship between initial clinical manifestation and long-term prognosis
      of patients with systemic lupus erythematosus.
AB  - The relationship between clinical manifestations and prognosis was examined and
      evaluated among systemic lupus erythematosus (SLE) patients. A total of 542
      patients with SLE were selected and divided into nine groups according to their
      main clinical manifestation at the time of initial diagnosis. The relationship
      between these clinical manifestations and long-term prognosis was evaluated in
      respect to the survival, remission, relapse rates, the development of a new
      clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE
      (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral
      vascular disease, or pneumonitis had poor survival rates with cause of death
      related to their major organ involvement. Patients with nephropathy or leukopenia
      had lower remission rates, and an increase in relapse rates was frequently
      recognized in patients with pneumonitis. Body damage (damage index) was higher in
      patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of
      the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and
      often observed in patients with autoimmune hemolytic anemia and arthritis. The
      majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and
      pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia
      as a new main manifestation had a poor outcome. The results of long-term
      prognosis in SLE greatly differed with respect to the initial clinical
      manifestation at the time of diagnosis.

PMID- 17029078
TI  - Reactive arthritis after influenza vaccination: report of a case.
AB  - We describe a patient with reactive arthritis (ReA) induced by influenza
      vaccination. A healthy 79-year-old Japanese man began suffering from migrating
      polyarthritis 2 days after receiving influenza vaccine. He proved negative for
      rheumatoid factor, showing no evidence for microbial infections such as
      Streptoccocci, Chlamydia, or Parbovirus B19. Human leukocyte antigen (HLA) typing
      analysis revealed positive results for HLA-B54 (22), which is one of the cross
      reactive antigens to HLA-B27. His arthritis improved with administration of
      nonsteroidal anti-inflammatory drugs, and recovery was attained within 6 weeks.
      Reactive arthritis is a rare adverse effect induced by influenza vaccination;
      however, it is important that it is recognized by all physicians.

PMID- 17029079
TI  - Intra-articular osteoid osteoma protruding from the acetabular fossa.
AB  - Osteoid osteoma is rarely found in the acetabular fossa. We treated a case of
      osteoid osteoma that had developed into a mass lesion and protruded from the
      acetabular fossa with synovitis. In this case, a well-defined bony tumor located
      in the acetabular fossa was detected by plain radiographs and computed tomography
      scans. Gadolinium-enhanced T1-weighted magnetic resonance (MR) images obtained
      with fat saturation indicated distinctive features in which the central area of
      the lesion and hyperemic synovium were enhanced. A surgical specimen contained
      the nidus, and osteoid osteoma was diagnosed. Retrospectively, this MR sequence
      demonstrated the characteristic nidus and synovitis, and it may thus be valuable
      in cases where diagnosis of intra-articular osteoid osteoma is difficult.

PMID- 17029080
TI  - Characteristic appearance of large subcutaneous gouty tophi in magnetic resonance
      imaging.
AB  - The development of multiple large tophi in patients with gout is rare. We report
      magnetic resonance (MR) and histological features of large subcutaneous tophi in
      a 32-year-old male patient with no known arthritis. His subcutaneous lesions were
      confused with a neoplastic process, evaluated by MR imaging, and surgically
      excised after biopsy. The honeycomb-like appearance on the gadolinium-enhanced
      images may reflect the characteristic multilobular structure of the tophi
      composed of avascular urate deposits and surrounding vascularized granulation
      tissue.

PMID- 17029081
TI  - The onset of Graves' disease during the clinical course of myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis.
AB  - A 47-year old man presented with atrial fibrillation, weight loss, hand tremor,
      and hyperperspiration concurrent with the reactivation of the disease activity of
      myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated
      glomerulonephritis. Laboratory findings indicated that the hyperthyroidism had
      already existed when glomerulonephritis was detected, and Graves' disease became
      evident while decreasing the dose of prednisolone. Although the levels of thyroid
      stimulating hormone receptor antibody, antithyroid peroxidase antibody, and
      myeloperoxidase antibody increased, both disease activities were suppressed by
      increasing the dose of prednisolone. This case indicates that MPO-ANCA-associated
      glomerulonephritis and Graves' disease may share a common pathogenesis.

PMID- 17029082
TI  - Total knee arthroplasty with a long-stemmed component for fractures adjacent to
      the knee in rheumatoid arthritis: a report of four cases.
AB  - Four rheumatoid arthritis patients with fractures adjacent to the knee were
      treated by total knee arthroplasty with a long-stemmed component. All four
      fractures healed; joint reconstruction and limb realignment were achieved
      simultaneously. Total knee arthroplasty with a long-stemmed component was useful
      in stabilizing the fracture and rapidly restoring function in the joint and the
      limb.

PMID- 17029083
TI  - No change of infliximab levels in stored blood for preoperative autologous blood
      donation: a preliminary report.

PMID- 17029084
TI  - Doppler sonographic evaluation of infliximab therapy for rheumatoid arthritis.

PMID- 17029085
TI  - Plantar heel pain and its 3-mode 4-stage treatment.
AB  - The most common cause for heel pain is plantar fasciitis. The diagnosis can
      usually be made by clinical examination, but sometimes ENMG
      (electroneuromyography), ultrasound, and magnetic resonance imaging examinations
      are helpful. Other reasons for heel pain, e.g., nerve entrapments,
      atherosclerosis/ischemia, and fat pad degeneration, should be excluded. Plantar
      fasciitis can also present a symptom of chronic seronegative
      spondyloarthropathies or reactive arthritis. In the case of common plantar
      fasciitis, three different modes of treatment can be administered, namely, (1)
      anti-inflammatory and analgesic treatment, (2) rest and diminution of the strain
      at the insertion, and (3) maintenance of the tension and flexibility of the soft
      tissues. A simple four-step treatment plan algorithm, based on symptoms, their
      duration, and response to treatment, is presented. Operative treatment is seldom
      needed if the algorithm is correctly followed. Operative treatment is recommended
      only when the pain remains resistant to conservative treatment after more than 1
      year. For operative treatment, partial release of the fascia close to insertion
      to avoid flat foot and secondary strain on the calcaneocuboid and midtarsal
      (Lisfranc) joints is our preferred option.

PMID- 17029086
TI  - Granzyme B and natural killer (NK) cell death.
AB  - Granzyme B is a unique serine protease, which plays a crucial role for target
      cell death. Several mechanisms of delivery of granzyme B to target cells have
      been recently identified. Granzyme B directly activates Bid, a specific substrate
      for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves
      many prominent autoantigens, and the hypothesis that autoantibodies arise when
      cryptic determinants are revealed to the immune system has been proposed. Some
      autoantibodies directed against granzyme B-specific neoepitopes are present in
      serum from patients with autoimmune diseases. In the tissues from autoimmune
      diseases, granzyme B might play an important role for disease progression (i.e.,
      rheumatoid arthritis synovium) or inhibition (i.e., regulatory T cells). We have
      identified a novel type of activation-induced cell death (granzyme B leakage
      induced cell death). Activation-induced natural killer (NK) cell death is
      accompanied by the leakage of granzyme B from intracellular granules into the
      cytoplasm, and it triggers apoptosis by directing Bid to mitochondrial membranes.
      An excess of "leaked" granzyme B over its inhibitor, serpin proteinase inhibitor
      9, is a major determinant of cell death. The role of granzyme B in autoimmunity
      and its influence on NK cell death are discussed.

PMID- 17029087
TI  - Therapeutic effects of the combination of methotrexate and bucillamine in early
      rheumatoid arthritis: a multicenter, double-blind, randomized controlled study.
AB  - Disease-modifying antirheumatic drug (DMARD) combination therapies are used
      widely, but there have been few reports clearly demonstrating that combination
      therapy is more effective than DMARD monotherapy. We conducted a multicenter,
      double-blind controlled trial in order to clarify that the combination of
      methotrexate and bucillamine is more effective than either alone. The subjects of
      this study were 71 patients with active rheumatoid arthritis within 2 years of
      onset. Dosages were 8 mg methotrexate with 5 mg folic acid per week (MTX group),
      200 mg bucillamine per day (BUC group), or both MTX and BUC (combination group).
      Clinical effects and adverse reactions were observed for 96 weeks. The ACR 20
      response rate was 79.2% in the combination group, significantly higher than the
      rates of 43.5% for the MTX group (P = 0.008) and 45.8% for the BUC group (P =
      0.0178). The cumulative survival curve of maintaining the ACR 20 response was
      significantly higher in the combination group than in the MTX and BUC groups (P =
      0.0123 and P = 0.0088, respectively). The mean increase in the total Sharp score
      over 96 weeks was 12.6 +/- 9.0 in the combination group, significantly lower (P =
      0.0468) than the value of 28.0 +/- 28.3 for the single DMARD (combined MTX and
      BUC) group. The incidence of adverse reactions did not differ significantly
      between the three groups. It was concluded that the combination therapy with MTX
      and BUC showed significantly higher clinical efficacy than either of the single
      DMARD therapies.

PMID- 17029088
TI  - A study of ten Japanese patients with seronegative spondylarthropathy: a
      tentative proposal.
AB  - We reviewed ten patients with seronegative spondylarthropathy (SNSA), who all
      fulfilled the European Spondylarthropathy Study Group criteria for
      spondylarthropathy (SpA); seven patients also met the Amor criteria for SpA.
      Seronegative spondylarthropathy was not a uniform syndrome but rather a wide
      spectrum of complex disease with characteristics of sacroiliitis and
      enthesopathy. The most frequent symptom at diagnosis of SNSA was inflammatory low
      back pain, followed by asymmetric oligoarthralgia and Achilles tendonitis and/or
      plantar fasciitis. Systemic complications were revealed as eye and skin
      involvement. Imaging methods including pelvic radiography, scintigraphy, and
      computed tomography scanning were useful in detecting spondylarthropathic
      changes, which were characteristic of SNSA. Human leukocyte antigen (HLA) typing
      showed various patterns among patients, in which HLA-B27 was positive in three
      patients with ankylosing spondylitis. HLA-B51, which is a well-known genetic
      factor associated with Behcet's disease (BD), was positive in two patients who
      were apparently distinct from BD. Two patients with palmoplantar pustulosis
      showed symptoms and signs characteristic of SNSA. Although we have few SNSA
      patients in the present study, we would like to propose that HLA-B51 positive SpA
      would be considered as a subset of SNSA, and that pustulotic SpA also would be
      classified as a member of SNSA. This led us to suggest the possibility to change
      the concept of SNSA proposed by Moll et al. The optimal treatment remains to be
      defined, but sulfasalazine was effectively used with almost all patients in
      combination with nonsteroidal anti-inflammatory drugs.

PMID- 17029089
TI  - Comparison in values of color flow signals and vascular resistance of synovial
      vascularity demonstrated by Doppler sonography between knee and
      metacarpophalangeal joints of patients with rheumatoid arthritis.
AB  - Synovial vascularity of 12 patients with rheumatoid arthritis (RA) was examined
      by Doppler sonography for color flow signals and vascular resistance on knee
      joints and metacarpophalangeal (MCP) joints, and the results were compared with
      each other and with C-reactive protein (CRP) levels of the patients. A
      significant correlation was observed between knee resistance index (RI) and MCP
      RI (P = 0.0140), but not between knee color flow signals and MCP color flow
      signals (P = 0.1029). A significant correlation was also observed between knee
      color flow signals and knee RI (P = 0.0107), and knee pulsatility index (PI) (P =
      0.0146). On the other hand, no correlation was observed between MCP color flow
      signals and MCP-RI (P = 0.828), and MCP-PI (P = 0.434). There was no significant
      correlation between CRP levels and grades of color flow signals, RI, and PI for
      both knee and MCP joints. Doppler sonographic evaluation of RI, especially knee
      RI, could be a useful marker for estimating synovial inflammation in RA patients.

PMID- 17029090
TI  - Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal
      ulcer in patients with rheumatoid arthritis in Japan.
AB  - We evaluated the prevalence of Helicobacter pylori infection and the association
      of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use
      with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with
      rheumatoid arthritis (RA). Using the clinical database of the cohort of RA
      patients and the serum titers of H. pylori antibody, 1815 patients were analyzed.
      Clinical data were successfully collected for 1529 patients over 2 years, and the
      history of NSAID use and the occurrence of newly diagnosed UGI ulcer were
      ascertained by patient self-reports and confirmed by their medical records. A
      total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of
      positivity for H. pylori in patients with and without NSAID use were 47.5% and
      54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58
      0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori-/NSAID-
      group, 1.24% in the H. pylori-/NSAID+ group, 1.06% in the H. pylori+/NSAID-
      group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori
      infection and NSAID for the occurrence of new UGI ulcers after adjusting for age
      and sex were 2.97 (95% CI: 1.19-7.38) and 4.31 (95% CI: 0.57-32.4), respectively.
      Although the prevalence of H. pylori antibody was low in patients with RA
      compared with that in healthy Japanese individuals, H. pylori infection was a
      significant risk factor for UGI ulcer in patients with RA.

PMID- 17029091
TI  - Macrophages that have phagocytosed particles are capable of differentiating into
      functional osteoclasts.
AB  - The aim of the current study was to determine whether human macrophages that have
      phagocytosed particles are capable of differentiating into osteoclastic bone
      resorbing cells. Macrophages isolated from human peripheral blood were cultured
      with latex particles in the presence of receptor activator of nuclear factor (NF)
      kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) on dentine
      slices and coverslips. After 24 h incubation, particles that had not yet been
      phagocytosed were removed by washing the slices. Histochemistry and
      immunohistochemistry was used to determine expression of macrophage and
      osteoclast markers and lacunae resorption, scanning electron microscopy, and
      transmission electron microscopy were used to examine cells with phagocytosed
      particles. Isolated macrophages on dentine slices were noted to contain a large
      number of particles inside, and no particles were identified outside of culture
      cells after washing. After 14 days of incubation, numerous tartrate-resistant
      acid phosphatase-positive multinucleated cells that contained particles in their
      cytoplasm, capable of extensive lacunae bone resorption, formed in these
      cultures. Our results clearly indicated that macrophages that have phagocytosed
      particles were still capable of differentiating into osteoclastic bone-resorbing
      cells. Macrophages that have phagocytosed wear particles in the pseudomembrane
      surrounding an implant not only produce cytokines but also may differentiate into
      functional osteoclasts, and influence bone resorption and loosening of a
      prosthesis.

PMID- 17029092
TI  - Bone resorption of the facet joint in rheumatoid arthritis as a predictor of
      lower cervical myelopathy.
AB  - The purpose of the present study was to identify the risk factors to predict
      instability of the subaxial cervical spine and cervical myelopathy based on plain
      radiographs. The study was performed on 99 patients with mutilating rheumatoid
      arthritis (RA). From plain lateral radiographs of the cervical spine over time,
      rheumatoid cervical spine lesions were investigated and evaluation was made on
      the possibility to develop cervical myelopathy. The incidence of subaxial
      cervical spine lesions in the patients with mutilating RA was as high as 98%. In
      particular, resorption of the superior facet suggests high risk to develop
      cervical myelopathy. The presence of spinous process erosion is also likely to
      reveal such a possibility. There was no statistically significant difference in
      the anteroposterior diameter of cervical spinal canal between the cases with
      cervical myelopathy and those without it. Resorption of the superior facet is the
      most important factor for the development of cervical myelopathy. In the cases
      with rheumatoid cervical spine lesions, it is necessary to take special notice of
      the superior facet.

PMID- 17029093
TI  - An unusual complication of familial Mediterranean fever: protracted arthritis
      with bilateral coxarthrosis and intraosseous amyloidosis of femoral head.
AB  - Protracted arthritis is uncommon in familial Mediterranean fever (FMF) and rarely
      may result in degenerative joint damage, a well-known complication of FMF,
      usually affecting kidneys. We present an unusual case of FMF involving severe
      bilateral coxarthrosis leading to residual incapacity that was treated by total
      hip arthroplasty, and an unusual presentation of amyloidosis - intraosseous
      amyloidosis of the femoral head.

PMID- 17029094
TI  - Massive mesenteric edema in a patient with type I hereditary angioedema.
AB  - We report a patient with hereditary angioedema (HAE) presenting with skin edema
      and abdominal pain. Laboratory examination showed reduced levels of CH50, C2, C4,
      and C1 inhibitor (C1-INH). Abdominal computed tomography (CT) showed marked
      mesenteric edema and wall thickening of the duodenum and transverse colon. Acute
      abdominal pain is common in HAE and is difficult to distinguish from surgical
      emergency. Massive mesenteric edema on CT is a rare, but specific, sign
      suggesting HAE.

PMID- 17029095
TI  - Utility of grommets for implant arthroplasty of the great toe in a patient with
      rheumatoid arthritis: a case report.
AB  - We report a case of rheumatoid arthritis treated by bilateral flexible hinge toe
      implant arthroplasty, using grommets only on one side, which resulted in
      bilateral fractures requiring removal of the implants 6.5 years after the
      surgery. Both implants were completely fractured at the bottom of the distal
      stems. Macroscopically, synovitis was present around both fractured stems,
      although the severity of synovitis and fragmentation of the fractured implant was
      relatively mild on the right side in which grommets were used. The shape of the
      body of the fractured implant was relatively preserved on the right side in which
      grommets were used. There was no damage or fracture of the grommets. The grommet
      might have acted to prevent pressures and scratches that would cause synovitis
      and deformity of the body of the implant, but might not completely prevent
      fractures of implants.

PMID- 17029096
TI  - A case of systemic lupus erythematosus presenting transverse myelitis after an
      episode of meningitis.
AB  - A 27-year-old woman suffering from systemic lupus erythematosus was admitted
      because she had motor and sensory palsy of the lower extremities, neck stiffness,
      and a fever. Cerebrospinal fluid study indicated meningitis, and magnetic
      resonance imaging revealed cord swelling and high signals at Th9-Th12 levels.
      Antibiotics treatment led to resolution of the meningeal signs. Intravenous
      cyclophosphamide and prednisolone resulted in a partial recovery from the
      transverse myelitis neurological disturbance.

PMID- 17029097
TI  - A case of systemic sclerosis sine scleroderma associated with perforation of an
      afferent loop after subtotal gastrectomy with Billroth 2 anastomosis for its
      severe gastrointestinal involvement.
AB  - A 50-year-old man was admitted to hospital for dysphagia. The upper
      gastrointestinal series revealed esophageal stricture, pyloric stenosis, and
      hypomotile small intestine. He was diagnosed with systemic sclerosis sine
      scleroderma with gastrointestinal involvement. After subtotal gastrectomy with
      Billroth 2 anastomosis, he had recurrent intestinal pseudo-obstruction and
      perforation of the afferent loop. Our experience indicates that surgical
      procedures in bowel scleroderma, in which an afferent loop is reconstructed,
      could easily cause perforation of the afferent loop.

PMID- 17029098
TI  - Human urinary trypsin inhibitor bolus infusion improved severe interstitial
      pneumonia in mixed connective tissue disease.
AB  - Interstitial pneumonia (IP) with mixed connective tissue disease (MCTD) often
      progresses despite immunosuppressive therapies that caused serious infections.
      Human urinary trypsin inhibitor (UT) inhibits inflammatory factors associated
      with IP, without immunosuppression. UT bolus infusion rescued a female MCTD
      patient with refractory IP and severe opportunistic fungal pneumonia. Her IP
      diminished with monthly UT bolus infusion despite tapering of prednisolone,
      without UT-related side effects. UT pulse therapy could prove beneficial for
      refractory IP in MTCD even with opportunistic infections.

PMID- 17029099
TI  - Asymptomatic interstitial pneumonitis induced by bucillamine in a patient with
      rheumatoid arthritis.

PMID- 17029100
TI  - Removal of dying cells and systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a very heterogeneous systemic autoimmune
      disease, in which autoantibody synthesis against nuclear constituents is the main
      immunological characteristic. These autoantibodies underwent affinity maturation
      and isotype switching. Additionally, T-cell tolerance against nuclear
      autoantigens should be affected in these autoimmune patients. Nuclear material
      derived from apoptotic and/or necrotic cells may serve as an important source of
      autoantigens. However, dead and dying cells as well as cellular debris are
      rapidly removed from tissues by phagocytes without eliciting inflammation or
      immune responses under healthy conditions. During apoptosis nuclear components
      are strongly modified through enzymatic reactions. If these cells are not timely
      cleared, those autoantigens may be released, taken up, and presented by dendritic
      cells in tissues or presented by follicular dendritic cells in lymph nodes to T
      and B cells, respectively. This could be a mechanism for breaking the peripheral
      self-tolerance. In this article we focus on the deficient clearance of apoptotic
      cells in SLE patients and its importance in development of this autoimmune
      disease.

PMID- 17029101
TI  - Involvement of cyclic guanosine monophosphate-dependent protein kinase II in
      chondrocyte hypertrophy during endochondral ossification.
AB  - During vertebrate skeletal development, the appendicular skeleton forms through
      endochondral ossification, which involves the intricately regulated multistep
      differentiation of mesenchymal cells. During this process, mesenchymal
      condensations initially differentiate into chondrocytes. Then chondrocytes in the
      center further differentiate into hypertrophic chondrocytes. Hypertrophic
      chondrocytes express a number of osteogenic factors and induce bone formation.
      Although numerous studies have provided novel insights into the regulation and
      function of cartilage development, little is known about the intracellular
      signaling pathways regulating chondrocyte hypertrophy. Recent study revealed that
      cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (cGKII) coupled
      the stop of proliferation and the start of hypertrophic differentiation of
      chondrocytes. Herein, we review the molecular mechanism of regulation of
      chondrocyte hypertrophy by cGKII and the interaction between cGKII and other
      signaling pathways.

PMID- 17029102
TI  - Pharmacokinetics, efficacy, and safety of short-term (12 weeks) etanercept for
      methotrexate-refractory polyarticular juvenile idiopathic arthritis in Japan.
AB  - We examined and evaluated the pharmacokinetics, efficacy, and safety of
      etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile
      idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA
      patients 4-17 years old received 0.4 mg of etanercept per kilogram of body weight
      subcutaneously twice weekly for up to 3 months in the open-label, prospective,
      and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%,
      or more from baseline in at least three of six indicators of disease activity,
      with no more than one indicator worsening by more than 30% from baseline (30%,
      50%, or 70% definition of improvement, respectively), and disease activity score
      (DAS28) by EULAR (European League Against Rheumatism) response criteria. At the
      end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both
      30% and 50% definition of improvement after etanercept treatment. To our
      surprise, 15 of 22 patients (68.2%) had a response with 70% definition of
      improvement. Moreover, in DAS28, eight patients were evaluated as having a good
      response and there were no patients with a poor response to etanercept. Treatment
      had to be stopped in one patient who developed joint contracture during the study
      period, but there were no significant adverse events in the other patients. In
      conclusion, treatment with etanercept leads to significant improvement in
      patients with active polyarticular JIA in Japan. Etanercept is well tolerated by
      pediatric patients as well as adults.

PMID- 17029103
TI  - Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy
      methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg
      capsule of methotrexate three times per week.
AB  - Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA);
      however, the pharmacodynamics of MTX in Japanese patients with RA treated
      legitimately according to the government recommended dosage, 6 mg per week, are
      unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured
      in sera of 16 outpatients with active RA in the first week of MTX treatment and 4
      12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of
      the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h.
      The mean maximal serum drug concentration (mean C(max)) of MTX attained at 1-2 h
      after ingestion of the first capsule was 0.215 and 0.252 microM, respectively, in
      the first and the follow-up week. The mean C(max) after ingestion of the third
      capsule was 0.223 microM and 0.357 microM. The mean C(max) of 7-OH MTX was 0.0334
      and 0.0289 microM for the first capsule, and 0.0495 and 0.0672 microM for the
      third capsule. The results indicate that MTX does not accumulate or deposit in
      the body of Japanese patients with RA when treated with 6 mg per week, and
      pharmacodynamics of MTX are comparable to those in overseas patients treated with
      7.5 mg per week.

PMID- 17029104
TI  - The study of bone mineral density and bone turnover markers in postmenopausal
      women with active rheumatoid arthritis.
AB  - The aim of this study was to investigate determinants of reduced bone mineral
      density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and
      to evaluate whether there are common markers of bone loss. We evaluated BMD of
      the femoral neck using dual-energy X-ray absorptiometry, and the measured
      biochemical markers included serum bone-specific alkaline phosphatase (BALP),
      serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I
      collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked
      immunsorbent assay, and OC was measured using an immunoradiometric assay. One
      hundred and forty postmenopausal Japanese women who had not received treatment
      with bisphosphonates or hormone replacement therapy were entered into the study.
      Thirty-four patients (41.0%) had femoral osteopenia (T score -1 to -2.5) and 23
      patients (27.7%) had osteoporosis (T < -2.5). The body mass index of patients
      with normal BMD (T score >or= -1.0) was significantly higher (P < 0.01) than in
      patients with osteoporosis at the femoral neck. The T score exhibited a
      significant negative correlation with age and the duration of RA disease. Serum
      BALP and serum OC, markers of osteoblast function, were negatively related to
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix
      metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function,
      exhibited a positive correlation with ESR, CRP, and MMP-3. From these results,
      this study suggests that generalized bone loss occurs in active RA and is
      characterized by evidence of bone resorption that is correlated with the high
      levels of inflammation. Body mass index, disease duration, and high serum NTx
      level were common risk factors in osteoporosis of postmenopausal women with RA.

PMID- 17029105
TI  - Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid
      arthritis patients after stimulation with monocytes.
AB  - It has been reported that nurse-like cells (NLCs) play a critical role in the
      pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs
      established from RA patients (RA-NLCs), and freshly isolated blood monocytes was
      analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were
      established from the synovium of RA patients. The RA-NLCs were cultured with
      monocytes freshly isolated from peripheral blood of healthy donors, and induction
      of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines
      was examined. The levels of IL-6 were over 400 times higher in the supernatant
      from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs
      alone. Anti-tumor necrosis factor (TNF)-alpha monoclonal antibody inhibited the
      induction of both cytokine in a dose-dependent fashion, although there was no
      detectable level of TNF-alpha in the supernatant from coculture. In addition,
      coculture of RA-NLCs and monocytes without direct cell contact did not induce
      cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes
      were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs
      contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured
      alone. The levels of IL-8 were also much higher (about 900 times) in the
      supernatant from coculture than in those from cultures of RA-NLCs alone.
      Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured
      alone. These results indicate that NLCs produce high levels of IL-6 and IL-8
      after cell-cell interaction with monocytes/macrophages via membrane-bound TNF
      alpha, and that activation of NLCs by monocytes/macrophages may be involved in
      the pathogenesis of RA through maintenance of synovial inflammation.

PMID- 17029106
TI  - Identification of three novel peptides that inhibit CD40-CD154 interaction.
AB  - The CD40-CD154 interaction is an attractive target for therapeutic intervention
      in various autoimmune disorders, including rheumatoid arthritis, systemic lupus
      erythematosus (SLE), multiple sclerosis, and myasthenia gravis. In this study, to
      develop a new disruption strategy of the CD40-CD154 interaction, we screened for
      peptides with inhibitory effects on such ligation. 2 x 10(11) phage display
      libraries displaying liner peptides of 12-mer amino acids were screened by CD40
      Ig binding assay and eight phages which expressed a different respective peptide
      (40BP-1 to -8) were able to specifically bind to CD40. Competitive inhibition
      analyses showed that 3 of the 8 peptides (40BP-N1-1 - APELPNMTPSWT; 40BP-N1-2 -
      APRPHTSYSPLP; and 40BP-N1-3 - GMTAPPPPRLTQ) blocked CD40-CD154 interaction when
      used at high concentrations. A consensus sequence (APxPPxxT) was conserved in
      these three peptides. These peptides may constitute a useful and novel strategy
      for the inhibition of the interaction between CD40 and CD154 molecules.

PMID- 17029107
TI  - Gouty flexor tenosynovitis of the hand mimicking atypical mycobacterial
      infection.
AB  - A 50-year-old Japanese fish dealer presented with painful and swollen fingers.
      Infectious flexor tenosynovitis with Mycobacterium marinum was suspected. Range
      of motion was restored after tenosynovectomy and after ofloxacin and
      clarithromycin were administered. Two years after the operation, the patient
      presented again with acute inflammation in the same fingers. Histopathological
      examination revealed gouty tenosynovitis. The preconception that mycobacterial
      infection occurs often in fish dealers caused us to miss the correct diagnosis of
      gouty tenosynovitis.

PMID- 17029108
TI  - An external snapping hip caused by osteochondroma of the proximal femur.
AB  - We herein report the findings of a 17-year-old boy who suffered from a right
      external snapping hip, which was caused by an osteochondroma of the proximal
      femur. He has been asymptomatic since the excision of the tumor. This case shows
      a rare etiology in which an external snapping hip occurred between the iliotibal
      band and the osteochondroma.

PMID- 17029109
TI  - A case of Epstein-Barr virus-associated natural killer/T-cell lymphoma presenting
      as dermatomyositis: extranodal relapse after 7 years in remission.
AB  - A 56-year-old Japanese man was admitted to our hospital due to a fever of unknown
      origin. He had had a history of extranodal natural killer (NK)/T-cell lymphoma,
      nasal type, and had been in complete remission for 7 years until June 2003, when
      he developed high fever, eyelid swelling, and muscular weakness. Serum creatine
      kinase levels were elevated. Histopathological examination of skin and muscle
      biopsy specimens revealed subcutaneous infiltration of lymphoid cells positive
      for CD3, CD56, and Epstein-Barr virus-encoded small nuclear RNA-1. We report this
      unique case of Epstein-Barr virus-associated lymphoma mimicking dermatomyositis.

PMID- 17029110
TI  - A case of systemic lupus erythematosus complicated with pneumatosis cystoides
      intestinalis.
AB  - Pneumatosis cystoides intestinalis (PCI), which is characterized by the presence
      of multiple gas-filled mucosal, submucosal, or subserosal cysts located
      throughout the colon and/or small intestine, is an unusual complication of
      systemic lupus erythematosus (SLE). We report a case of a 33-year-old woman with
      a 5-year history of SLE with PCI. Her symptoms improved with conservative
      management. Although PCI is a rare manifestation of SLE, clinicians should be
      alert to the differential diagnosis of this complication.

PMID- 17029111
TI  - Beneficial effect of complementary alternative medicine on lymphedema with
      rheumatoid arthritis.
AB  - Lymphedema of the limbs can be an added complication in a small number of
      rheumatoid arthritis cases, becoming a long-standing problem even when there is
      good control of inflammatory joint disease. In the present article, we describe a
      patient with RA who developed lymph-edema of the forearms successfully treated
      with TJ-48 (Juzentaihoto) as a complementary alternative medicine (CAM). This
      kind of edema does not seem to show any consistent relationship with the severity
      of arthritis in the literature surveyed. In contrast, lymphedema in this case
      improved in parallel with RA disease activity. We discuss the utility of CAM
      treatments and review the literature.

PMID- 17029112
TI  - Asynchronous progressive diaphyseal dysplasia.
AB  - We report the case of a 42-year-old Japanese woman with unusual diaphyseal
      dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the
      cortex with resultant enlargement of the diaphysis, unclear demarcation of the
      surface of the cortex, and no periosteal reaction. These changes were found on
      the left femur at the first presentation, and those on the right femur developed
      within several years. Although this patient partly presented characteristics of
      Ribbing disease and Camurati-Engelmann disease, the focal involvement of
      bilateral femora suggested an unknown pathogenesis.

PMID- 17029113
TI  - Rheumatoid arthritis-associated corneal ulceration complicated by bacterial
      infection.
AB  - We report two cases of rheumatoid ocular disease complicated by infection of
      methicillin-sensitive Staphylococcus aureus (MSSA) in one case, and methicillin
      resistant Staphylococcus aureus (MRSA) in the other. In both cases, punctal
      occlusion and immunosuppressive therapy were presumed to be major risk factors of
      the infections. In addition, the characteristic feature was corneal melting,
      which is probably accelerated by infection. To avoid infectious progression and
      melting, potent antibiotics followed by immunosuppressive therapy were necessary.

PMID- 17029114
TI  - Lack of relationship between mannose-binding lectin variant alleles and risk of
      arterial thrombosis in Japanese patients with systemic lupus erythematosus.

PMID- 17029115
TI  - Apoptosis and cerebral ischemic reperfusion injury developed after haemorrhagic
      shock: experimental study.
AB  - BACKGROUND: Apoptosis is a process of programmed cell death that plays a role in
      some normal and pathological conditions. In this study, we investigated the
      apoptosis during cerebral ischemic reperfusion injury in response to haemorrhagic
      shock in a rat model. METHODS: Thirty-six adult Sprague-Dawley rats were divided
      into six groups: control, haemorrhagic shock (HS), ischemic reperfusion (IR), 1st
      hour IR, 3rd hour IR, 6th hour IR and 24th hour IR. Rats were sacrificed by
      taking blood from intracardiac area after finishing the experiment. The tissues
      were fixed using neutral buffered 10% formaldehyde solution for histopathological
      examination. Tissues were stained immunohistochemically with APO 2.7 and positive
      expression apoptotic cells were counted using a Clemex Vision Lite 3.5 vision
      analysis system. RESULTS: There were 2-3 apoptotic cells in the control group
      (group 1) and this number increased to 8-11 in the haemorrhagic shock group
      (group 2) (p<0.05). Secondary or more serious injury occurs during ischemic
      reperfusion injury. The number of apoptotic cells increased to 11-14 at the 1st
      hour (group 3) and it was significant as compared to group 2 (p<0.05). The number
      of apoptotic cells significantly increased to 15-17 by the 3rd hour (group 4) as
      compared to group 3 (p<0.05). While there was no additional increase by the end
      of the 6th hour (group 5) as compared to group 4, the number of apoptotic cells
      significantly increased to 18-24 by the end of 24th hour (group 6) as compared to
      group 5 (p<0.05). CONCLUSION: The majority of injuries to the brain following
      haemorrhagic shock occur during ischemic reperfusion. We observed that apoptosis
      increases step by step on the 1st, 3rd and 24th hours after ischemic reperfusion
      injury.

PMID- 17029116
TI  - Bone marrow-derived osteoblasts seeded into porous beta-tricalcium phosphate to
      repair segmental defect in canine's mandibula.
AB  - BACKGROUND: Bone regeneration is often needed for many aesthetic and
      reconstructive procedures. Tissue engineering provided a promising approach to
      supplement existing treatment strategies. In this study, we aimed to evaluate the
      effect of reconstructing mandibular defect by using bioceramics seeded with bone
      marrow derived osteoblasts. METHODS: Canine's autologous marrow stromal cells
      were Culture-expanded and induced to osteoblastic phenotype, then were seeded
      into prepared porous beta-tricalcium phosphate, after being incubated in vitro.
      The cell/ scaffold complexes were implanted into the prepared defect in canines'
      mandibula and fixed by internal rigid fixation. In control groups, beta
      tricalcium phosphate alone and autologous iliums were implanted into the prepared
      defects. Twelve weeks after implantation, the specimens were examined
      macroscopically and histologically. RESULTS: In experimental group and autologous
      iliums group, new bone grafts were successfully developed at 12 weeks after
      implantation and repaired the continuity of the mandibula. Histologically, newly
      formed bone could be observed on the surface and in the pores of beta-tricalcium
      phosphate in the cell/scaffold group, whereas incomplete bone repair was found in
      pure beta-tricalcium phosphate group. CONCLUSION: The harvested bone marrow
      derived osteoblasts possess the ability to form new bone tissue when seeded onto
      porous beta-tricalcium phosphate, which shows the potential of using this method
      to repair large segmental mandibular defect clinically.

PMID- 17029117
TI  - The efficacy and immunogenicity of Pneumo-23 and ACT-HIB in patients undergoing
      splenectomy.
AB  - BACKGROUND: The objective of this prospective study is to validate the efficiency
      of Streptococcus pneumoniae and Haemophilus influenzae vaccines in splenectomized
      patients via the demonstration of seroconversion and uninterrupted ability for
      opsonization. METHODS: Thirty-two adult patients (18 males, 14 females; mean age
      46.1 years; range 18 to 79 years) who underwent elective or urgent splenectomy
      for various benign and malignant hematological disorders, splenic trauma and
      splenic masses were reviewed. Pneumo-23 and Act-HIB were administered to all
      patients on routine basis. In order to demonstrate the ongoing opsonizing
      capacity of the immune system and the seroconversion of immunoglobulins after
      vaccination, antibody titers of IgG and IgM and plasma C3 and C4 levels were
      quantitatively measured. RESULTS: The operative morbidity was 9% and overall
      mortality was 16%, with no early postoperative death in this series. Five
      patients with various malignant disorders died due to dissemination of their
      primary tumor. None of the patients with benign hematological disorders or those
      with splenic trauma died during the mean follow-up of 427 days. Furthermore,
      death from overwhelming postsplenectomy infection was nil in our clinical survey.
      All of the patients including those with malignancy had normal IgG (mean: 1383.1
      mg/dL) and IgM levels (mean: 80.9 mg/dL) during discharge and at the last follow
      up. Among the patients with benign hematological disorders, splenic trauma and
      splenic masses necessitating splenectomy, C3 and C4 levels were entirely within
      normal limits with a mean of 108.8 mg/dL and 21.4 mg/dL, respectively.
      CONCLUSION: This preliminary study reveals adequate seroconversion of
      immunoglobulins in all patients and normal C3 and C4 levels in patients with
      benign hematological disorders and splenic trauma. Moreover, none of the patients
      in the latter group had S. pneumoniae or H. influenzae infection nor did they
      expire due to overwhelming sepsis during the follow-up period. Long-term follow
      up is required to determine the continuation of this immunologic response and the
      necessity of repeated vaccination.

PMID- 17029118
TI  - [The use of the laryngeal mask airway and the cuffed oropharyngeal airway during
      percutaneous tracheostomy].
AB  - BACKGROUND: The aim of our study is to compare the safety and efficiency of the
      use of the laryngeal mask airway (LMA) and the cuffed oropharyngeal airway (COPA)
      with the use of endotracheal tube (ETT) for maintain patent airway during
      percutaneous tracheostomy (PCT). METHODS: The patients were randomly assigned to
      LMA group (n=35, M/F; 28/7, age; 52 [18-79]), COPA group (n=31, M/F; 23/8, age;
      57 [18-80]) and ETT group (n=30, M/F; 22/8, age; 49 [18-80]) with respect to use
      of LMA, COPA and ETT in order to maintain patent airway during PCT procedure. PT
      was performed as described by Griggs et al. Complications occurred during and
      after PCT procedure and airway manipulations required to maintain a patent airway
      were recorded. RESULTS: Duration of PT was longer in the ETT group comparing with
      the other groups (for both groups; p<0.01). The LMA failed to maintain patent
      airway in 1 of 35 patients (2.9%) and the COPA failed to maintain patent airway
      in 3 of 31 patients (9.7%). The airway intervention required to maintain patent
      airway was found to be higher in the COPA group (45.2%) than in the LMA group
      (11.4%) (p<0.01). There was no significant difference with respect to the
      complications between the groups. CONCLUSION: In our study, LMA and COPA were
      inserted easily during PCT with high success rates, but airway manipulations were
      higher in the COPA group. In our opinion, supra/infraglottic airway devices to
      maintain patent airway during PCT should be chosen according to patient's status
      and physician's experience.

PMID- 17029119
TI  - [The effects of informing patients and their relatives on satisfaction at
      emergency units].
AB  - BACKGROUND: The research was performed to determine the effect of adding a
      service unit planned to be carried out by nurses into the current emergency work
      flow on the patient satisfaction. METHODS: The research was carried out on 300
      patients who were discharged from an University Hospital Emergency Department in
      Turkey between 21 January 2002 and 22 March 2002. The data of the research were
      collected by using Patient Identification Form, Nurse Activity Form, The
      Evaluation Form for Service of Giving Information and Patient Follow-up Form. The
      patients were informed by the information booklet developed by the researcher,
      their questions were answered and a copy of the information booklet was given to
      the patients and/or their families. The patients were called from their homes or
      offices one week after their discharge from the hospital and their satisfaction
      levels of the information given by the researcher were questioned. The data
      collected from the research were analyzed in computer by using percentage, chi
      square and the significance test for universe rate. RESULTS: It was determined
      that the level of patient satisfaction was increased when the information was
      given together with the booklet about their diseases, treatments and the cares
      and it was also understood that calling the patients to be followed was
      essential. CONCLUSION: It is suggested that the informations should be given to
      the patients and their relatives on discharge by the nurses and new information
      booklets should be developed.

PMID- 17029120
TI  - [The evaluation of bicycle accidents that were admitted to a pediatric emergency
      department].
AB  - BACKGROUND: We planned this study to evaluate trauma cases secondary to bicycle
      driving in childhood and to draw attention to the importance of the regulation of
      traffic rules, the education of bicycle drivers, and the importance of helmet
      usage. METHODS: Data in this study were obtained by retrospective review of the
      files of trauma cases admitted to the Pediatric Emergency Unit of Trakya
      University Medical Faculty between January 2003 and August 2005. Patients' age,
      gender, clinical signs, type of injury, season of the event and percentage of
      hospitalization were obtained from hospital records. RESULTS: Fifteen (24.6%) of
      61 cases who were admitted to our emergency unit were females and 46 (75.4%) were
      males. The types of trauma of all patients who suffered from bicycle accidents
      were as following: 42 (68.9%) head trauma, 29 (47.5%) extremity trauma, 49
      (80.3%) soft tissue trauma, 2 (3.3%) abdominal trauma, and one case of urogenital
      trauma. Also multiple traumas were present in most of these cases. Thirteen
      patients had extremity fractures and three had cranial fractures. None of the
      bicycle drivers were using helmets at the time of the trauma. CONCLUSION: Bicycle
      drivers should have specific education, helmet use must become widespread and
      special traffic regulations have to be settled.

PMID- 17029122
TI  - Conservative management of a grade V renal trauma associated with a grade III
      hepatic lesion: is it possible?
AB  - Conservative management of solid abdominal organ injuries has been increasing and
      challenging trauma surgeons. This case report describes a successful non
      operative management of a grade V renal lesion associated to a grade III hepatic
      lesion. Such lesions have not been described in conjunction in the revised
      literature.

PMID- 17029121
TI  - [The factors affecting the morbidity and mortality in chest trauma].
AB  - BACKGROUND: We evaluated thoracic trauma cases with respect to etiologic causes,
      other system injuries accompanying to the thoracic trauma, treatment methods and
      outcomes and the prognostic factors affecting the need for thoracotomy, length of
      hospital stay, morbidity and mortality in the light of relevant literature data.
      METHODS: A retrospective evaluation was performed on 141 patients (102 males
      (72.3%), 39 females (27.7%); mean age 40; range 8 to 89 years) who were treated
      for thoracic trauma in our center between July 2003 and December 2005. RESULTS:
      117 patients (83%) had blunt and 24 (17%) penetrating thoracic trauma. Isolated
      thoracic trauma and multisystem trauma were found in 48 (34%) and 93 (66%)
      patients, respectively. Mean white blood cell count was 12.560+/-5.7 (5-25 x 103
      /uL) at admission. The number of patients who met lung injury scale criteria for
      grade I, grade II, grade III and grade IV were 19 (13.5%), 12 (8.5%), 25 (17.7%)
      and 13 (9.2%), respectively. Hypotension was determined in 16 patients (11.3%)
      during admission. With regard to treatment, while symptomatic conservative
      management was satisfactory in 76 patients (53.9%), tube thoracoscopy and
      thoracotomy were performed in 59 (41.8%) and 11 (7.8%) patients respectively. The
      morbidity was seen in 30 patients (21.3%). The mortality rate was 7.8% (n=11).
      CONCLUSION: The high white blood cell count, high lung injury scale grade, 3 and
      more rib fractures and accompanying head injury were determined as the prognostic
      factors affecting the morbidity and mortality.

PMID- 17029123
TI  - [Pneumatosis intestinalis mimicking free intraabdominal air: a case report].
AB  - A 47-year-old male patient had undergone endoscopic balloon dilatation six times
      due to pyloric stenosis however the result was not satisfying. Surgical treatment
      was considered. Chest X-ray revealed free sub-diaphragmatic air but there were no
      acute abdomen signs clinically. In abdominal computerized tomography, there were
      small intestinal loops anterior to the liver and there was gas collection, which
      can not be differentiated exactly between an extraluminal free air and the one in
      the bowel wall of adjacent small bowel segments. In the emergency surgery cysts
      filled with gas in the wall of distal ileal segments were seen. Pneumatosis
      intestinalis should be kept in mind in the differential diagnosis of free
      intraabdominal air.

PMID- 17029124
TI  - [Traumatic aneurysm of the superficial temporal artery: a case report].
AB  - Traumatic aneurysm of superficial temporal artery is an uncommon lesion. Blunt
      traumas of war, firearm, motorized vehicle and sport injuries are common causes.
      In this case, traumatic aneurysm of superficial temporal artery that occurs after
      scalp trauma in 74 years old male patient, was reported. Patient who suffers from
      a mass in his forehead ten days after trauma was admitted to our clinic.
      Selective angiography of the right temporal artery was performed as traumatic
      aneurysm was suspected upon the findings of physical examination and cranial
      computerized tomography studies. The aneurysm was detected. The proximal and
      distal part of the aneurysm was ligated and it was totally removed under general
      anesthesia. The histopathological investigation confirmed the presence of the
      traumatic aneurysm. Especially in hairy skin injuries, traumatic lesions should
      be considered as an aneurysm. Diagnosis, treatment, and surgical strategy must be
      planned by the help of these informations.

PMID- 17029125
TI  - [Longitudinal clival fractures: a report of three cases].
AB  - Fractures of the clivus are often associated with severe head trauma and have
      high mortality rates due to coexisting injury of the adjacent vessels, brain stem
      and lower cranial nerves. An early diagnosis is often not possible because of
      adherent problems, high mortality rate and inadequacy of emergency imaging.
      Diagnosis has recently become easier with high resolution bone window computed
      tomography studies. In this study, radiological and clinical findings of three
      patients with longitudinal clival fractures and severe head trauma have been
      presented and associated injuries and prognostic issues are discussed with
      reference to the limited number of similar cases in the English literature.

PMID- 17029126
TI  - Survival of an eight-year-old child with a very severe high-tension electrical
      burn injury: a case report.
AB  - We present the management and survival of an eight-year-old boy with a severe
      high-tension electrical burn injury of 68% of total body surface area in a
      surgical intensive care unit, as a result of a well-planned and applied treatment
      strategy. Subsequent to escharotomy and fasciotomy operations under general
      anesthesia, the patient was taken into the surgical intensive care unit. In
      addition, patient underwent nine more operations including right femur
      disarticulation and split-thickness skin graftings with homografts from his
      brother and autografts. The patient was connected to mechanical ventilator for 59
      days. By the time the patient was transferred to plastic and reconstructive
      surgery ward, he was fully conscious, cooperated and hemodynamically stable.

PMID- 17029127
TI  - Outbreak of cutaneous Rhizopus arrhizus infection associated with karaya ostomy
      bags.
AB  - BACKGROUND: We investigated an outbreak involving 2 patients hospitalized at
      hospital A with cutaneous Rhizopus arrhizus (oryzae) infections of surgically
      created stomas. METHODS: A cohort study involving all patients having ileostomy
      or colostomy surgery during the outbreak period (January-April 2005) was
      performed. Environmental samples, including samples obtained from nonsterile
      karaya (a plant-derived adhesive) ostomy bags and from select hospital areas,
      were collected. A point prevalence survey was conducted at 5 unrelated hospitals
      to assess stoma care practices and mold contamination of karaya ostomy bags
      outside of hospital A. Zygomycete isolates were identified by standard methods.
      RESULTS: Infections occurred 7 and 10 days after operations for the 2 patients; 1
      patient died. In a 21-patient cohort, receiving the equivalent of > or =0.5 mg/kg
      per day of prednisone during the week prior to the index date was associated with
      infection (infection rate, 33% for patients receiving > or =0.5 mg/kg per day of
      prednisone vs. 0% for patients receiving <0.5 mg/kg per day of prednisone;
      P=.07). The time to first ostomy bag change was longer for patients with
      infection (median duration, 8.5 days; range, 7-10 days) than for the 19 patients
      without infection (median duration, 1.5 days; range, 1-17 days; P=.08). At
      unrelated hospitals, the median time to first ostomy bag change was 2 days
      (range, 1-6 days) for 18 patients after ostomy. R. arrhizus was recovered from 10
      of 18 karaya ostomy bags from hospital A and from karaya ostomy bags donated from
      3 of 5 other hospitals, but it was not recovered from the hospital A environment.
      CONCLUSIONS: The initial karaya ostomy bag was likely to be the source of
      Rhizopus infection, and prolonged exposure before the first ostomy bag change
      might have precipitated infection in these susceptible individuals. Karaya might
      contain opportunistic molds that can pose an infectious risk among susceptible
      persons.

PMID- 17029128
TI  - No effect of pyridoxine on the incidence of myelosuppression during prolonged
      linezolid treatment.
AB  - Complications of long-term linezolid administration include anemia and
      thrombocytopenia. A recent report has suggested that pyridoxine may prevent
      myelosuppression. Pyridoxine was administered to 24 patients with bone infections
      who were being treated with linezolid. Thrombocytopenia occurred in 11 patients
      (45.8%), and anemia occurred in 6 (25%). We concluded that treatment wtih
      pyridoxine is unlikely to benefit patients who have been receiving linezolid for
      >2 weeks.

PMID- 17029129
TI  - Progression of Pneumocystis jiroveci pneumonia in patients receiving echinocandin
      therapy.
AB  - Echinocandins are a novel class of antifungal drugs that target beta (1, 3)-D
      glucan synthesis. Animal studies have shown that these agents have activity
      against Pneumocystis jiroveci infection; however, clinical data are lacking. We
      reviewed all cases of proven P. jiroveci pneumonia (PCP) in non-human
      immunodeficiency virus-infected patients at our hospital over a 5 year period
      (2001-2005). Two patients received conventional PCP treatment and concomitant use
      of echinocandins for presumed invasive aspergillus. In both cases, PCP
      progressed, and the patient died. The use of echinocandins in the prevention or
      treatment of PCP cannot be recommended without evidence to support their
      effectiveness.

PMID- 17029130
TI  - The clinical assessment, treatment, and prevention of lyme disease, human
      granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the
      Infectious Diseases Society of America.
AB  - Evidence-based guidelines for the management of patients with Lyme disease, human
      granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis),
      and babesiosis were prepared by an expert panel of the Infectious Diseases
      Society of America. These updated guidelines replace the previous treatment
      guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The
      guidelines are intended for use by health care providers who care for patients
      who either have these infections or may be at risk for them. For each of these
      Ixodes tickborne infections, information is provided about prevention,
      epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the
      doses and durations of antimicrobial therapy recommended for treatment and
      prevention of Lyme disease and provide a partial list of therapies to be avoided.
      A definition of post-Lyme disease syndrome is proposed.

PMID- 17029131
TI  - Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2
      vaccine preparations.
AB  - BACKGROUND: Influenza A/H9N2 viruses can infect humans and are considered to be a
      pandemic threat. Effective vaccines are needed for these and other avian
      influenza viruses. METHODS: We performed a phase I, randomized, double-blind
      trial to evaluate the safety and immunogenicity of a 2-dose schedule
      (administered on days 0 and 28) of 4 dose levels (3.75, 7.5, 15, and 30 microg of
      hemagglutinin) of inactivated influenza A/chicken/Hong Kong/G9/97 (H9N2) vaccine
      with and without MF59 adjuvant. Vaccine safety was assessed with a diary and
      selected blood tests. Immunogenicity was measured using serum hemagglutination
      inhibition (HAI) and microneutralization (MNt) antibody assays. RESULTS. Ninety
      six healthy adults (age, 18-34 years) were enrolled in the study. Arm discomfort
      was more common in groups that received adjuvant, but adverse effects of the
      vaccination were generally mild. Geometric mean serum HAI and MNt antibody titers
      to the influenza A/chicken/Hong Kong/G9/97 (H9N2) virus strain for all vaccine
      groups were similar on day 0 but were significantly higher (P<.001) on both days
      28 and 56 for the MF59-adjuvanted vaccine groups than for groups given
      nonadjuvanted vaccine. Other measures of immunogenicity were also higher in the
      adjuvanted vaccine groups. HAI and MNt geometric mean titers measured after the
      administration of a single dose of MF59-adjuvanted vaccine were similar to those
      measured after 2 doses of nonadjuvanted vaccine. CONCLUSIONS: The combination of
      MF59 adjuvant with a subunit vaccine was associated with improved immune
      responses to an influenza A/H9N2 virus. The adjuvanted vaccine was immunogenic
      even after a single dose, raising the possibility that a 1-dose vaccination
      strategy may be attainable with the use of adjuvanted vaccine.

PMID- 17029132
TI  - Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a leading cause of congenital illness and
      disability, including hearing loss and mental retardation. However, there are no
      nationwide estimates of CMV seroprevalence among pregnant women or the overall
      population of the United States. METHODS: To determine CMV prevalence in a
      representative sample of the US population, we tested serum samples for CMV
      specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the
      third National Health and Nutrition Examination Survey (1988-1994). RESULTS: The
      prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV
      seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to
      90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or
      ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic
      black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences
      in CMV seroprevalence persisted when controlling for household income level,
      education, marital status, area of residence, census region, family size, country
      of birth, and type of medical insurance. Among women, racial and/or ethnic
      differences were especially significant; between ages 10-14 years and 20-24
      years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non
      Hispanic white persons, and <1% for Mexican Americans. CONCLUSIONS: On the basis
      of these results, we estimate that each year in the United States approximately
      340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and
      50,000 Mexican American women of childbearing age experience a primary CMV
      infection. Given the number of women at risk and the significance of congenital
      disease, development of programs for the prevention of CMV infection, such as
      vaccination or education, is of considerable public health importance.

PMID- 17029133
TI  - Cytomegalovirus infection: back to the future or no more elephants?

PMID- 17029134
TI  - Risk factors and outcome among a large patient cohort with community-acquired
      acute hepatitis C in Italy.
AB  - BACKGROUND: The epidemiology of acute hepatitis C has changed during the past
      decade in Western countries. Acute HCV infection has a high rate of chronicity,
      but it is unclear when patients with acute infection should be treated. METHODS:
      To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and
      to assess the rate of and factors associated with chronic infection, we enrolled
      214 consecutive patients with newly acquired hepatitis C during 1999-2004. The
      patients were from 12 health care centers throughout the country, and they were
      followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver
      tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146
      patients (68%) had symptomatic disease. The most common risk factors for
      acquiring hepatitis C that were reported were intravenous drug use and medical
      procedures. The proportion of subjects with spontaneous resolution of infection
      was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days
      (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting
      hepatitis experienced HCV RNA clearance within 3 months of disease onset.
      Multiple logistic regression analyses showed that none of the variables
      considered (including asymptomatic disease) were associated with increased risk
      of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the
      importance of medical procedures as risk factors in the current spread of HCV
      infection in Italy. Because nearly all patients with acute, self-limiting
      hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance
      within 3 months of disease onset, it seems reasonable to start treatment after
      this time period ends to avoid costly and useless treatment.

PMID- 17029135
TI  - Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from
      humans: predictor for a severe clinical outcome.
AB  - BACKGROUND: Some Escherichia coli produce Shiga toxin (Stx) in which cytotoxicity
      is increased (activated) by intestinal mucus and elastase (Stx2d(activatable)).
      These strains are highly virulent in mice, but their association with human
      disease is poorly understood. We investigated the prevalence of
      Stx2d(activatable) among Stx-producing E. coli (STEC) isolated from humans and
      the association between production of this Stx and the clinical outcome of
      infection. METHODS: A total of 922 STEC isolates obtained from patients with
      hemolytic uremic syndrome or bloody or nonbloody diarrhea or from asymptomatic
      carriers were tested for the gene encoding Stx2d(activatable) by PCR and PstI
      restriction analysis. The toxin activatibility by human and mouse intestinal
      mucus and by an elastase was determined by quantifying the cytotoxicity using the
      Vero cell assay. RESULTS: The stx(2d-activatable) gene was identified in 60
      (6.5%) of 922 STEC strains; in 31 of these strains, it was the sole stx gene.
      Thirty of these 31 strains produced Stx2d(activatable). All of them lacked the
      intimin-encoding eae gene. Among eae-negative STEC, which typically cause mild
      diarrhea or asymptomatic infection, production of Stx2d(activatable) was
      significantly associated with the ability to cause severe disease, including
      bloody diarrhea (P<.001), and with systemic complications, such as hemolytic
      uremic syndrome (P<.001). CONCLUSIONS: Production of Stx2d(activatable) by the
      infecting STEC may predict a severe clinical outcome of the infection, with
      progression to hemolytic uremic syndrome. A prompt and comprehensive subtyping of
      stx genes in STEC isolates is necessary to alert the treating physician that a
      patient is at risk of developing hemolytic uremic syndrome, even though the
      infecting STEC lacks eae.

PMID- 17029136
TI  - What makes an enterohemorrhagic Escherichia coli?

PMID- 17029137
TI  - Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of
      traveler's diarrhea: a randomized, double-blind, controlled study.
AB  - BACKGROUND: Diarrhea is the most common illness associated with international
      tourism. We evaluated the efficacy of a probiotic preparation of nonviable
      Lactobacillus acidophilus (hereafter referred to as LA) for the prevention of
      traveler's diarrhea. METHODS: We conducted a randomized, double-blind, controlled
      trial. Travelers were randomized to receive either LA or placebo twice daily from
      1 day before their departure to 3 days after their return. On each day of the
      trip and the week following the return, travelers had to record the number and
      consistency of stools and their adherence to the treatment. Diarrhea was defined
      as > or =3 unformed stools in a 24-h period. RESULTS: From January 2001 to
      September 2004, a total of 174 subjects were randomized to each treatment group.
      Half of the travelers went to West Africa, and organized tours or backpacking
      were the most common modes of traveling. The incidence of diarrhea did not differ
      between the 2 groups; it was 61.4 cases per 100 person-months in the LA group
      (95% confidence interval [CI], 44.1-85.5) and 43.4 cases per 100 person-months in
      the placebo group (95% CI, 30.0-62.9) (P=.14). Adjustment for travel duration and
      other variables did not reveal any difference between the 2 groups (adjusted
      hazard ratios comparing the LA and placebo groups were 1.43 [95% CI, 0.87-2.36]
      in an intent-to-treat analysis and 1.38 [95% CI, 0.79-2.39] in an efficacy
      analysis). CONCLUSIONS: There was no beneficial effect of treatment with LA for
      the prevention of travelers' diarrhea. More studies are required to assess the
      efficacy of other specific probiotics (e.g., a Lactobacillus rhamnosus GG
      preparation) for preventing traveler's diarrhea.

PMID- 17029138
TI  - An elderly woman with abdominal pain and Fever.

PMID- 17029139
TI  - VisualDx: decision-support software for the diagnosis and management of
      dermatologic disorders.
AB  - The VisualDx system (http://www.logicalimages.com/prodVDx.htm) is a JAVA-based
      decision-support program developed by Logical Images to be used in clinical care
      to develop differential diagnoses based upon morphologic finding- and patient
      finding-driven searching. It consists of several modules, many of which are very
      relevant to infectious diseases specialists, such as Fever & Rash; International
      Travel; Drug Eruptions; Smallpox Vaccination; Terrorism Recognition;
      Immunocompromised, HIV or AIDS; Female Genital Rashes & Growths; and Male Genital
      Rashes & Growths. Unlike books and atlases indexed by disease, with VisualDx,
      clinicians can enter patient descriptors and lesion morphologies, resulting in
      rapid assistance with differential diagnosis. VisualDx also increases clinician
      awareness of, knowledge about, and skills in the recognition of chemical warfare,
      bioterrorism, and radiation injuries.

PMID- 17029140
TI  - Illness in travelers visiting friends and relatives: a review of the GeoSentinel
      Surveillance Network.
AB  - Travelers returning to their country of origin to visit friends and relatives
      (VFRs) have increased risk of travel-related health problems. We examined
      GeoSentinel data to compare travel characteristics and illnesses acquired by 3
      groups of travelers to low-income countries: VFRs who had originally been
      immigrants (immigrant VFRs), VFRs who had not originally been immigrants
      (traveler VFRs), and tourist travelers. Immigrant VFRs were predominantly male,
      had a higher mean age, and disproportionately required treatment as inpatients.
      Only 16% of immigrant VFRs sought pretravel medical advice. Proportionately more
      immigrant VFRs visited sub-Saharan Africa and traveled for >30 days, whereas
      tourist travelers more often traveled to Asia. Systemic febrile illnesses
      (including malaria), nondiarrheal intestinal parasitic infections, respiratory
      syndromes, tuberculosis, and sexually transmitted diseases were more commonly
      diagnosed among immigrant VFRs, whereas acute diarrhea was comparatively less
      frequent. Immigrant VFRs and traveler VFRs had different demographic
      characteristics and types of travel-related illnesses. A greater proportion of
      immigrant VFRs presented with serious, potentially preventable travel-related
      illnesses than did tourist travelers.

PMID- 17029141
TI  - Recurrent benign lymphocytic meningitis.
AB  - Recurrent benign lymphocytic meningitis is a recurring, typically innocuous,
      painful form of aseptic meningitis. This syndrome is associated with transient
      neurological symptoms in one-half of afflicted patients. The causative agent is
      usually herpes simplex virus type 2, which can be confirmed by detection of viral
      DNA in the cerebrospinal fluid using polymerase chain reaction. Clinical disease
      resolves spontaneously; however, acyclovir, valacyclovir, and famciclovir have
      been administered to some patients for both episodic therapy and suppression of
      recurrences. This therapy is thought to be beneficial, although there is no
      controlled trial data to support efficacy and safety.

PMID- 17029142
TI  - HIV-associated monoclonal gammopathy: a retrospective analysis of 25 patients.
AB  - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is unusual
      in the general population aged <60 years. Various reports indicate a much higher
      incidence of monoclonal gammopathy among human immunodeficiency virus (HIV)
      infected patients and a significantly younger age at diagnosis. We sought to
      describe the laboratory findings and clinical course of MGUS, including
      association with plasma cell disorders, other malignancies, and infections, in 25
      HIV-infected patients with a detectable serum monoclonal protein. METHODS: We
      reviewed the patients' demographic characteristics, stage of HIV infection, and
      clinical course. Laboratory studies included determination of CD4(+) T lymphocyte
      cell counts, HIV type 1 loads, and quantitative immunoglobulin levels; serum and
      urine protein immunoelectrophoresis; and determination of serum viscosity
      indices. Skeletal surveys and bone marrow biopsies were performed in selected
      cases. RESULTS: Twenty-four of 25 patients were male, and the median age of
      patients was 50 years (range, 21-69 years). The median CD4(+) T lymphocyte count
      was 350 cells/ microL (range, 40-1029 cells/ microL; mean, 355 cells/ microL),
      and the median HIV load was <75 copies/mL (range, <50 to 100,000 copies/mL; mean,
      20,800 copies/mL). Thirteen of 25 patients had HIV viremia, despite receiving
      highly active antiretroviral therapy (HAART). After a mean follow-up duration of
      21 months, 7 patients (28%) received a diagnosis of a malignancy (multiple
      myeloma, in 1 patient; non-Hodgkin lymphoma, in 1; Hodgkin lymphoma, in 1; Kaposi
      sarcoma, in 2; and plasmacytoma, in 2). Ten patients were coinfected with
      hepatitis B virus and/or hepatitis C virus; 6 were anemic. No patients developed
      renal failure or hypercalcemia. Nine (56%) of 19 evaluable patients had a
      decrease of serum monoclonal protein (mean, 0.5 g/dL) while receiving HAART.
      CONCLUSIONS: Patients in our study were characterized by the detection of a
      monoclonal protein at a younger age and the increased presence of other viral
      infections (infection with hepatitis B or C virus or Kaposi sarcoma herpesvirus)
      than is typically seen in an HIV-uninfected cohort. CD4(+) T lymphocyte counts
      were relatively robust. HAART appeared to have a favorable impact on the serum
      monoclonal protein level in 9 patients. Long-term follow-up is needed to better
      define the natural history of MGUS and the link to other possible contributing
      factors.

PMID- 17029143
TI  - Monoclonal gammopathy associated with HIV infection.

PMID- 17029144
TI  - Coinfection with hepatitis C virus increases lymphocyte apoptosis in HIV-infected
      patients.
AB  - To test the role of hepatitis C virus (HCV) in CD4 cell depletion in human
      immunodeficiency virus (HIV)-coinfected patients, T cell apoptosis was measured
      by annexin V labeling in 31 HIV-infected and 30 HIV-HCV-coinfected patients who
      were not receiving antiretroviral therapy. Apoptosis in naive CD4(+) T cells and
      in naive and memory CD8(+) T cells was significantly higher in HIV-HCV-coinfected
      than in monoinfected patients.

PMID- 17029145
TI  - John McFadyean and the centenary of the first isolation of Campylobacter species.
AB  - Campylobacter species recently emerged as a leading cause of acute diarrhea in
      humans, but it is not generally known that these species were first cultured from
      samples from aborting ewes as far back as 1906. This took place in the United
      Kingdom during a study that spanned several years of epizootic abortion in cattle
      and sheep. The chief investigator in this major undertaking was John McFadyean, a
      little-known yet remarkable man who founded veterinary pathology in Britain and
      who made immense contributions to public health. A brief portrayal illustrates
      his uncompromising dedication to scientific accuracy and to his profession, often
      in the face of opposition.

PMID- 17029148
TI  - Meta-analysis of diagnostic test accuracy.

PMID- 17029149
TI  - Randomized, controlled trials of directly administered antiretroviral therapy for
      HIV-infected patients: questions about study population and analytical approach.

PMID- 17029151
TI  - Colonization or infection with multidrug-resistant Acinetobacter baumannii may be
      an independent risk factor for increased mortality.

PMID- 17029152
TI  - Antituberculosis therapy and imatinib for chronic myeloid leukemia.

PMID- 17029153
TI  - Variant IS1016 insertion elements in invasive Haemophilus influenzae type b
      isolates harboring multiple copies of the capsulation b locus.

PMID- 17029154
TI  - Prevalence of influenza B during the 2004-2005 season in Japan.

PMID- 17029155
TI  - In support of Dr. Thomas Butler.

PMID- 17029156
TI  - Prevention of perioperative hypothermia with forced-air warming systems and upper
      body blankets.
AB  - Forced-air warming is known as an effective procedure in prevention and treatment
      of perioperative hypothermia. Hypothermia is associated with disturbances of
      coagulation, raises postoperative oxygen consumption by shivering, increases
      cardiac morbidity, leads to a higher incidence of wound infection, and prolongs
      hospital stay. Additionally, preoperative local warming reduces the incidence of
      wound infection after clean surgery. In an animal experiment it has been
      demonstrated that even during large abdominal operations the major source of heat
      loss was the skin. Although evaporation accounted for the largest heat loss from
      the abdominal cavity, it was a minor source due to the smaller heat losing area.
      As a consequence, reduction of heat loss from the skin is the most promising
      approach to avoid hypothermia. During abdominal surgery and lower-limb surgery,
      the use of upper blankets is favourable. The use of upper-body blankets implies a
      reduction of heat loss in a relevant area and, furthermore, a heat gain. The
      covered area is approximately 0.35 m2, or approximately 15%-20% of body surface.
      The heat balance in this area can be changed by 46.1W to 55.0W by forced-air
      warming systems with upper body blankets. Depending on the surgical procedure and
      resulting fluid demand, forced-air warming with upper-body blankets-in
      combination with insulation and fluid warming-is an effective method to prevent
      perioperative hypothermia.

PMID- 17029157
TI  - Current status of laparoscopic ultrasound.
AB  - The purpose of this chapter is to introduce the beginning surgeon
      ultrasonographer to the use of ultrasound during laparoscopic surgery. The
      authors routinely use ultrasound in the intraoperative, endoscopic, and office
      settings. The importance of ultrasound in the various surgical specialties is
      well documented in the literature. Since the introduction of minimally invasive
      techniques to General Surgery, many advanced applications of ultrasonography have
      been developed. Confident examinations of intraabdominal anatomy, pathologic
      conditions, and therapeutic procedures can readily be performed. In this chapter,
      a comprehensive introduction to laparoscopic ultrasound is presented to the
      practicing General Surgeon. The basic equipment requirements and setup are
      explained. Fundamental techniques of laparoscopic ultrasound examination are
      described. The authors' method of screening for common bile duct stones during
      routine laparoscopic cholecystectomy is illustrated. Examination of the normal
      biliary tree with helpful hints is presented. The authors' systematic technique
      of visualizing the normal liver parenchyma is described. Common benign and
      malignant findings are elucidated. A brief synopsis of pancreatic ultrasonography
      with attention to pathologic findings is provided. Uses of ultrasound in
      unanticipated situations are introduced. With perseverance, the reader will
      discover that laparoscopic ultrasound skills can be readily attained.

PMID- 17029158
TI  - Diagnostic validity of radio-guided sentinel node mapping for gastric cancer: a
      review of current status and future direction.
AB  - Diagnostic validity of sentinel node (SN) mapping has been recently introduced
      into the field of various solid tumors, including gastrointestinal (GI) cancer.
      In gastric cancer, acceptable detection rates of SNs, as well as sensitivity in
      detecting micrometastasis based on SN status, was reported using the dye-guided
      method, as well as the radio-guided method. Gastric cancer is currently one of
      the suitable targets of SN navigation surgery among visceral tumors. Despite the
      multi-directional and complicated lymphatic flow from gastric mucosa, the
      anatomical situation of the stomach is relatively suitable for SN mapping in
      comparison with organs embedded in closed spaces, such as the esophagus and
      rectum. In particular, clinically T1N0 gastric cancer seems to be a good entity
      for which to try to modify the therapeutic approach. From the data reported in
      the literature, micro-metastases tend to be limited within the sentinel basins in
      cT1N0 gastric cancer. Sentinel basins are, therefore, good targets of selective
      lymphadenectomy for cT1N0 gastric cancer with the potential risk of
      micrometastasis. Furthermore, laparoscopic local resection is theoretically
      feasible for curative treatment of SN negative early gastric cancer. For
      laparoscopic application of SN mapping of gastric cancer, a radio-guided method
      is essential. Although recent single institutional studies support the validity
      of the SN concept, a multi-centric prospective validation study based on a
      standardized protocol is essential for further clinical application. Currently,
      two major well-designed clinical trials of SN mapping for gastric cancer open
      surgery have been initiated in Japan. Radio-guided SN mapping for gastric cancer
      has a great potential to provide a new paradigm shift for surgical management of
      an early gastric cancer.

PMID- 17029159
TI  - Management of intra-abdominal abscess due to surgical site infection.
AB  - Intra-abdominal abscesses are one of the major complications that occur after
      Gastrointestinal Surgery. Therapeutic modalities include drainage and irrigation.
      This study describes the development of a new drainage and continuous irrigation
      system that results in less skin irritation and reduced dressing changes. This
      system involved the use of the Surgidrain open top (ALCARE, Tokyo, Japan), which
      consists of a sealing sheet with a drainage lumen and plastic cap. A double-lumen
      tube was inserted into the abscess cavity through a slit in the plastic cap. The
      abscess cavity could, therefore, be irrigated continuously through one lumen of
      the double-lumen tube, and most of the fluid could be drained through the second
      lumen of the double-lumen tube. Overflow fluid was drained through the Surgidrain
      open top drainage lumen. This system enabled better protection against skin
      complications and the ability to easily flush the abscess intermittently.

PMID- 17029161
TI  - Laparoscopic sleeve gastrectomy (LSG): review of a new bariatric procedure and
      initial results.
AB  - OBJECTIVE: To evaluate the outcomes and initial results of laparoscopic sleeve
      gastrectomy (LSG) and review of the literature. METHODS: A retrospective analysis
      of the initial ten patients who underwent LSG was performed. Study endpoints
      included operative time, complication rates, hospital length of stay, and
      percentage of excess body weight loss. RESULTS: This study included five women
      and five men, with a mean age of 43 (range: 31-52) years. Their mean preoperative
      weight was 182 kg (range: 125 kg-247 kg), with a mean preoperative body mass
      index (BMI) of 64 (range: 61- 80). Indication for LSG was the importance of BMI
      in all patients. One patient had previous restrictive bariatric surgery. Mean
      operative time was two (range: 1.5-2.5) hours. No patients required conversion.
      No postoperative complications nor mortality were noted. The median hospital stay
      was 7.2 days. Average excess body weight loss and BMI at one year were 51% and 23
      kg/m2, respectively. CONCLUSIONS: LSG can be integrated safely into a bariatric
      treatment program with good results in terms of weight loss and quality of life.
      LSG can be a first-step procedure before gastric bypass or duodenal switch, or a
      one-step restrictive procedure if long-term results are good. LSG should be
      considered as a surgical option in the bariatric field, but further studies are
      needed to determine its exact use.

PMID- 17029160
TI  - Clinical applications of commercially available video recording and monitoring
      systems: inexpensive, high-quality video recording and monitoring systems for
      endoscopy and microsurgery.
AB  - The exclusive charge-coupled device (CCD) camera system for the endoscope and
      electronic fiberscopes are in widespread use. However, both are usually
      stationary in an office or examination room, and a wheeled cart is needed for
      mobility. The total costs of the CCD camera system and electronic fiberscopy
      system are at least US Dollars 10,000 and US Dollars 30,000, respectively.
      Recently, the performance of audio and visual instruments has improved
      dramatically, with a concomitant reduction in their cost. Commercially available
      CCD video cameras with small monitors have become common. They provide excellent
      image quality and are much smaller and less expensive than previous models. The
      authors have developed adaptors for the popular mini-digital video (mini-DV)
      camera. The camera also provides video and acoustic output signals; therefore,
      the endoscopic images can be viewed on a large monitor simultaneously. The new
      system (a mini-DV video camera and an adaptor) costs only US Dollars 1,000.
      Therefore, the system is both cost-effective and useful for the outpatient clinic
      or casualty setting, or on house calls for the purpose of patient education. In
      the future, the authors plan to introduce the clinical application of a high
      vision camera and an infrared camera as medical instruments for clinical and
      research situations.

PMID- 17029162
TI  - Current aspects of surgical management of GERD.
AB  - Gastroesophageal reflux disease (GERD) is one of the most common pathologies
      treated by primary care physicians. Despite advances in antacid pharmacological
      treatments, many patients remain refractory to maximal medical therapy. In
      addition, many others are either unable to tolerate the side effects of the drugs
      or simply are unwilling to receive life-long daily medications. Laparoscopic
      Nissen fundoplication has evolved as the surgical procedure of choice for
      patients with GERD. Although the durability of surgical management has been
      questioned, experienced surgeons achieve long-term reflux cure rates of about 85%
      to 95%. Barrett's esophagus has recently been considered an additional indication
      for surgical therapy of reflux due to evidence of dysplasia regression following
      a 360 degrees fundoplication. However, the timing of surgical intervention and
      the exact procedure for patients with both short- and long-segment Barrett's
      esophagus remains debatable. Esophageal dysmotility in surgical patients with
      GERD has traditionally been approached by "tailoring" the degree of
      fundoplication. Recent evidence suggests that partial fundoplication may not be
      effective and that full fundoplication should still be employed. The degree of
      dysmotility prohibitive to a full 360 degrees fundoplication remains
      controversial and should be addressed with future randomized trials. Finally,
      patients with failed fundoplication represent a formidable diagnostic dilemma and
      a technical challenge. In experienced hands, these patients can still benefit
      from minimally-invasive restorative or "re-do" fundoplications with minimal
      perioperative morbidity and good long-term results.

PMID- 17029163
TI  - Initial clinical experience with telemetrically adjustable gastric banding.
AB  - BACKGROUND: The feasibility and safety of laparoscopic adjustable gastric banding
      for treatment of morbid obesity has been demonstrated in a large number of
      studies. Access port-related complications constitute a significant part of all
      complications related to gastric banding. Further, adjustment of hydraulic
      gastric bands can be fairly lengthy, uncomfortable, and is not a precise
      procedure. A study was performed to assess the usefulness and efficacy of a new
      type of band adjusted telemetrically without the need for an access port. The
      initial worldwide results of the first telemetrically adjustable gastric band for
      morbid obesity (EASYBAND EndoArt Medical Technologies, Switzerland) in two German
      academic centers are described herein. METHODS: EASYBAND is a purely mechanical
      gastric band, in which adjustment is achieved by means of an embedded micromotor,
      controlled by an external control unit using telemetry. The exact band diameter
      is displayed continuously during adjustment on the external control unit screen.
      Thirty-seven patients, means 36 +/- 8 (range: 22-60) years, 7 (19%) men and 30
      (81%) women, with a mean body mass index (BMI) of 44.1 +/- 4.5 (range: 35.6
      59.6), were implanted using the standard laparoscopic technique during the period
      from June 2005 to October 2005. Prospective data were collected on all morbidly
      obese patients who underwent laparoscopic telemetrically adjustable gastric
      banding (LTAGB). RESULTS: No serious adverse events occurred during the operative
      period or immediately postoperatively in relation to the device. A mean of 3.0 +/
      0.6 adjustments per patients were performed during the follow-up schedule at
      one, three and six months. The band diameter was set to 29 mm (fully open) at
      implantation, 24.5 mm +/- 0.5 mm at one month, 23.3 mm +/- 0.7 mm at three
      months, and 23.0 mm +/- 1.0 mm at six months. The mean percent excess weight loss
      was 10.2% +/- 4.5% at one month, 23.8% +/- 8.8% at three months, and 30.2% +/-
      10.5% at six months. CONCLUSION: This initial study shows that the new
      telemetrically adjustable gastric banding device is implanted and operated
      safely, allows for atruamatic band adjustments with superior patient comfort, and
      leads to early excess weight loss comparable to that achieved by other gastric
      bands. Longer-term follows and larger population studies are needed to establish
      the final safety and performance profile of the telemetric gastric band.

PMID- 17029164
TI  - Stapled hemorrhoidectomy.
AB  - The procedure of stapled hemorrhoidectomy has been established as a safe and
      effective method for treating symptomatic hemorrhoids not responsive to more
      conservative measures. This chapter discusses the issues of safety, efficacy,
      durability, and cost of this procedure. In addition, we outline techniques for
      performing the procedure safely and effectively.

PMID- 17029165
TI  - Thyroid surgery: new approach to dissection and hemostasis.
AB  - The essential objectives for thyroidectomy are avoidance of injury to the
      recurrent laryngeal nerves (RLNs), conservation of the parathyroid glands, an
      accurate haemostasis, and an excellent cosmesis. In the last 10 years, major
      improvements and new technologies have been proposed and applied in thyroid
      surgery, among these mini-invasive thyroidectomy, regional anaesthesia, and
      intraoperative neuromonitoring. Moreover, new devices for achieving dissection
      and haemostasis have been proposed. The purpose of ligating vessels is to
      maintain the surgical site free from an excess of blood and reduce blood loss in
      patients. This chapter reviews relevant medical literature published in the
      English language since 1990 on thyroid surgery techniques with well-controlled
      trials on haemostasis and dissection. Searches were last updated October 2005.

PMID- 17029166
TI  - Laparoscopic cholecystectomy: past, present, and future.
AB  - Laparoscopic cholecystectomy is one of the most commonly undertaken procedures in
      General Surgery with more than 500,000 performed annually. Overall, the
      complication rate is less than 1.5%, and the mortality rate is less than 0.1%. As
      such, laparoscopic cholecystectomy was considered by most to be at its zenith
      since its inception in the early 1990 s. Advancements in technology and equipment
      have opened new doors to physicians and allowed the laparoscopic cholecystectomy
      to once again evolve. Traditional four-port cholecystectomy has given way to
      three- and even two-port techniques. Standard 12-mm ports have been replaced by 2
      mm ports, and experiments have now been implemented to achieve cholecystectomy
      with no ports-known as the transgastric technique. The authors reviewed evolution
      of these techniques that included a synopsis of our experience with the three
      port cholecystectomy, as well as the future direction of laparoscopic surgery.

PMID- 17029167
TI  - Laparoscopic low anterior resection for rectal cancer.
AB  - More so than with other types of colon cancer, rectal cancer is associated with a
      range of laparoscopic surgical techniques. Treatment of cancer of the lower
      rectum requires favorable operative fields, minimal contact with the tumor during
      dissection, and delicate surgical procedures to avoid nerve damage. Such surgery
      thus requires immobilizing the trunk so the patient can be repositioned as
      needed, placing ports at appropriate locations, as well as careful handling of
      surgical equipment. To minimize the risk of disseminating cancer cells during the
      procedure, the surgery should be restricted to patients with early-stage cancer.
      The most difficult surgical procedure is resection of the lower rectum. While
      safe resection of the intestinal tract was difficult using previously available
      surgical equipment, newly developed equipment makes today's resections much safer
      and easier. Indications for surgical intervention should be broadened carefully,
      based on a deeper understanding of the surgical anatomy within the pelvis and on
      various relevant oncological and technical factors.

PMID- 17029168
TI  - Laparoscopic-assisted colectomy: technique and discussion.
AB  - Minimally invasive surgery has undergone rapid development over the last 20 years
      and has greatly impacted the field of General Surgery. Removal of the appendix
      and gallbladder by way of laparoscopic means has become standard in surgical
      training and care. More complex procedures also are becoming incorporated into
      surgical resident education and routine clinical practice. Colon cancer
      operations, previously performed by an open approach to ensure adequate resection
      of the specimen and draining lymph nodes, are currently being performed
      laparoscopically by experienced surgeons with equivalent recurrence, morbidity,
      and overall mortality rates. In this chapter, the technique of laparoscopic
      colectomy is described and advantages and disadvantages are discussed. The
      literature is reviewed and this technique compared with the open procedure. The
      authors contend that laparoscopic colectomy is a suitable, and perhaps
      preferable, alternative to open procedures for benign or malignant colon disease,
      with acceptable long-term results.

PMID- 17029169
TI  - Bioactive prosthetic material for treatment of hernias.
AB  - HYPOTHESIS: Laparoscopic herniorrhaphy using Surgisis (Cook Surgical,
      Bloomington, IN, USA) mesh is an effective long-term treatment for repair of
      inguinal hernia. PATIENTS AND INTERVENTION: Between August 1999 and April 2005,
      67 patients underwent laparoscopic inguinal hernia repair by the total
      extraperitoneal (TEP) mesh placement technique using Surgisis mesh. A total of 82
      primary direct, indirect, pantaloon, and femoral hernias were repaired using this
      technique. MAIN OUTCOME MEASURES: Postoperative complications and recurrence as
      evaluated at two weeks, six weeks, three months, six months, one year, and yearly
      thereafter for up to five years. RESULTS: The operations were performed
      successfully on all the patients. One revision was done to an open procedure.
      Postoperative complications were typical of inguinal hernia surgery. Average
      follow up was 38 (range: 4-72, median: 35 months. Four non-technical recurrences
      following repair of direct hernias were reported, which indicates a 4.9%
      recurrence rate. No recurrences of indirect hernias were noted. CONCLUSIONS:
      Laparoscopic inguinal herniorrhaphy using Surgisis mesh is effective in treatment
      of primary inguinal hernias in adults with minimal complications and recurrence
      up to five years of follow up.

PMID- 17029170
TI  - Endoscopic extraperitoneal inguinal hernioplasty: disposable and reusable
      instruments.
AB  - Endoscopic totally extraperitoneal inguinal hernioplasty, TEP, has become an
      established technique for repair of inguinal hernia. The performance of TEP
      usually requires a number of disposable instruments. The high cost of these
      devices has been a deterrent to development of laparoscopic surgery. Success in
      cost containment is pivotal to enhance a wider application of TEP and benefit
      more patients, particularly in public hospitals. The differences in the design
      and material of disposable and reusable instruments account for distinction in
      their handling and safety attributes. Replacement of disposable instruments by
      reusable ones sometimes requires modification of surgical techniques. Reusable
      instruments are economically advantageous, but they require sterilization. Wear
      and tear of these reusable tools after multiple procedures sometimes causes
      unexpected problems during operation. This chapter reviews the pros and cons of
      reusable and disposable instruments for performance of TEP. The selection of
      reusable or disposable instruments should balance the cost of the procedure,
      convenience of the operation theatre, safety of the patient, and experience of
      the surgeon. Instruments, whether reusable or disposable, should offer value for
      money.

PMID- 17029171
TI  - What is next in inguinal hernia surgery?
AB  - Traditionally, the inguinal hernia repair is performed through an incision in the
      groin. Different kinds of operations are suggested as best repairs by using the
      patient's own tissue, or use of prosthetic mesh to reinforce the abdominal wall.
      The advent of the laparoscopic repair that also uses prosthetic mesh, made it
      even more complex to determine the best repair. Using the Evidence Based Medicine
      (EBM) principles, endpoints of the treatment are not only based on recurrence
      rates, but also on complications, patient satisfaction, convalescence, and costs.
      Several meta-analyses concluded that use of mesh is superior to the non-mesh
      operations. More difficult to determine is which mesh repair, open or
      laparoscopically, is the best. The laparoscopic repair is difficult and less
      suitable for general practice, but the open-mesh repair results in a higher
      percentage of chronic postoperative pain. Further research should be focused on
      making the laparoscopic repair less complicated, and development of new meshes
      for open surgery that reduce the amount of persistent postoperative pain.

PMID- 17029172
TI  - Laparoscopic myomectomy: a report of 982 procedures.
AB  - We have reported the experience of two referral laparoscopic gynecologic centers
      in Italy considering the results of almost 1000 laparoscopic myomectomies,
      including complication rate and fertility outcome. From January 1991 to December
      2003, a total of 982 single or multiple laparoscopic myomectomies (LM) were
      performed. Indications were infertility, recent and significant uterine
      enlargement, and other symptoms such as pelvic pain, menometrorrhagia, and
      abnormal bleeding. All surgical procedures were performed by three surgeons in
      two different endoscopic centers. Surgery outcome and information about
      subsequent fertility and obstetric outcome were reported. Myomectomies were
      performed using a standard technique with three ancillary suprapubic ports. In
      cases of deep intramural myomas, we injected the myomas with vasoconstrictive
      agents. A vertical incision of the serosa was made and mechanical enucleation of
      the myomas was performed whenever possible. A suture in one or two layers with
      large, curved needles (CT 1, 30 mm) swaged to polyglactin 1 or 0 sutures was
      performed. Extraction of the removed myomas took place with electric
      morcellation. Most patients (47%) had more than one myoma, with a maximum of
      eight per patient (average myomas removed for patients: 2.23). Myoma size ranged
      from 1 cm to 20 cm (average 67.20 mm +/- 27.1 mm). Most of the myomas (75%) were
      intramural. The average drop in hemoglobin concentration was 1.06 g +/- 0.86
      g/100 ml. The duration of the entire procedure ranged from 30 min to 360 min with
      a mean of 104.5 min. The conversion rate to laparotomy was 1.29% and no major
      intraoperative complications occurred. The mean postoperative hospital stay was
      2.02 days +/- 0.61 days and we had three serious postoperative complications. The
      overall rate of intrauterine pregnancy following LM was 62.53% and the abortion
      rate was 15.9%. Data suggest that laparoscopic myomectomy is a safe and reliable
      procedure, even in the presence of multiple or very enlarged myomas, with a low
      complication rate and satisfying long-term results.

PMID- 17029173
TI  - Adhesiolysis in severe and reccurent cases of adhesions related disorder (ARD) -
      a novel approach utilizing lift (gasless) laparoscopy and SprayGel adhesion
      barrier.
AB  - We investigated the feasibility and outcome of adhesiolysis in patients with
      severe and reccurent adhesions using lift (gasless) laparoscopy and a SprayGel
      adhesion barrier at the Institute for Endoscopic Gynecology (EndoGyn). The design
      included a prospective evaluation of lift (gasless) laparoscopic adhesiolysis in
      combination with a SprayGel adhesion barrier. A new score for bowel adhesions was
      developed and applied. All 35 patients with severe and reccurent adhesions
      underwent a lift-laparoscopic adhesiolysis with the Abdo-Lift and SprayGel
      adhesion barrier, a second-look laparoscopy at Day 7 and, in case of continuation
      of pain, a third-look laparoscopy within 6 months after the initial surgery. All
      patients were operated upon without conversion to laparotomy. The reduction in
      the adhesion score of adhesions at the second-look laparoscopy was overall (sum)
      89.8% (90.1% reduction in extent, 89.3% reduction in severity, and 89.9%
      reduction in grade). Five patients (14.3%) had a third-look laparoscopy within 6
      months after the initial surgery, in which four cases of adhesion reformation
      were confirmed. However, the scores were reduced compared to the initial surgery,
      especially in grade (94.2%) and severity (93.2%). In these analyses, SprayGel was
      uniquely effective in improving the success rates of adhesiolysis when combined
      with lift (gasless) laparoscopy and good hemostasis techniques. Adhesiolysis with
      Abdo-Lift and SprayGel had unparalleled efficacy in the adhesiolysis procedure
      even in those patients in whom other solutions have not worked. An overall
      reduction of adhesions by 89.9% at second-look laparoscopy was found. Even if
      five patients (14.3%) required a third-look laparoscopy where four cases of
      adhesion reformation were confirmed, the scores were reduced when compared to the
      initial surgery, especially in grade and severity.

PMID- 17029174
TI  - Laparoscopic Myomectomy.
AB  - Laparoscopic myomectomy (LM) is an increasingly accepted method of treatment for
      symptomatic uterine leiomyomas. It affords patients a minimally invasive surgery
      compared to the more traditional abdominal approach. Studies have shown the
      benefits of decreased blood loss, shorter hospital stay and recovery period, as
      well as decreased postoperative pain and fever in comparison to abdominal
      myomectomy (AM). Even myomas larger than 5 cm can be laparoscopically resected
      safely in the hands of an experienced surgeon. To date, studies indicate a
      decreased adhesion rate with the laparoscopic approach compared to the abdominal
      procedure. The use of adhesion barriers may decrease this rate further. In
      infertile women with myomas, pregnancy and live-birth rates improve following LM,
      and appear to be comparable with those rates achieved following AM. The data
      regarding the risk of uterine rupture in pregnancy following LM is limited.
      However, small studies show safe outcomes when patients are managed with the same
      degree of caution one might employ with post-abdominal myomectomy patients. In
      performing LM, a precise and diligent technique should be exercised to ensure a
      secure, multilayer closure.

PMID- 17029175
TI  - Advanced technologies for cardiac valvular replacement, transcatheter innovations
      and reconstructive surgery.
AB  - Since the 2002 Surgical Technology International monograph on valvular
      prostheses, there have been significant developmental and investigative advances.
      Aortic bioprostheses and mechanical prostheses have undergone design changes to
      optimize hemodynamics and prevent patient-prosthesis mismatch to have a potential
      satisfactory influence on survival. There has been continual technological
      improvements striving to bring forward advances that improve the durability of
      bioprostheses and reduce the thrombogenicity of mechanical prostheses. There also
      has been a continuance to preserve biological tissue with glutaraldehyde, rather
      than clinically evaluate other cross-linking technologies, by controlling or
      retarding calcification with therapies to control phospholipids and residual
      aldehydes. The techniques of mitral valve reconstruction have now been well
      established and new annuloplasty rings have been designed for the potential of
      maintaining the anatomical and physiological characteristics of the mitral
      annulus. Several objectives exist for annuloplasty, namely remodeling of the
      length and shape of the dilated annulus, prevention of dilatation of the annulus,
      and support for the potentially fragile area after partial-leaflet resection.
      Currently, there exists an emergence of catheter-based therapies for management
      of aortic stenosis and mitral regurgitation. For management of selected
      populations with critical aortic stenosis, techniques for aortic valve
      substitution have been developed for both antegrade and retrograde catheter
      techniques, as well as apical transventricular implantation. Mitral regurgitation
      has been addressed by experimental transcoronary sinus, stent-like devices and
      transventricular, edge-to-edge leaflet devices. The devices, descriptions and
      pictorial images comprise this monograph.

PMID- 17029176
TI  - Mitral valve: toward complete repairability.
AB  - During the last 50 years, there has been an exponential increase in our
      understanding of the structure and function of the mitral valve in health and
      disease. Large numbers of patients have undergone mitral-valve reparative
      procedures worldwide with variable results. In our initial 10-year experience in
      which traditional techniques were used for repair of mitral regurgitation, a 70%
      success rate was achieved. In 1995, a critical reappraisal of the common causes
      of failure to repair, or failure of repair and developed improved surgical
      approaches for these patients began. The conditions addressed were massive
      bileaflet prolapse ("Barlow's valves"); anterior leaflet prolapse; multisegment
      chordal failure; commissural accessory leaflet tissue prolapse; and leaflet
      destruction by endocarditis. A widely applicable standard technique was developed
      that the author and colleagues called the "American Correction." It emphasizes
      chordal replacement with polytetrafluoroethylene (PTFE) artificial chordae,
      importance of the line of apposition of the leaflets, and importance of
      simultaneous dynamic adjustment of the chordal length and anteroposterior
      dimension of the mitral annulus. In addition, use of multiple techniques in 30%
      of patients to complete the repair has been emphasized. These techniques resulted
      in a 90% repairability rate for all pathologies and 100% for myxomatous-mitral
      insufficiency. These techniques also have led to a decline in reoperation rates,
      and improved long-term durability. Continued evaluation with intraoperative and
      postoperative three-dimensional (3-D) echo provides further insights and
      refinement of mitral-repair techniques.

PMID- 17029177
TI  - Early mobilization after aortic valve surgery.
AB  - In recent years, the focus in peri-operative care of cardiac patients has shifted
      from trying to create a stress-free environment to hasten the recovery of
      patients by providing early extubation, early mobilization, and enteral
      nutrition. Fast-track cardiac surgery has therefore made a paradigm shift in
      postoperative care. However, evidence on the safety of early postoperative
      mobilization in high-risk groups like aortic valve replacement surgery is
      lacking. Physiological evidence from controlled studies in patients undergoing
      aortic valve replacement (AVR) showed that heart rate increases and stroke volume
      falls with maintenance of cardiac output. However, the increase of 50% to 60% of
      oxygen consumption during mobilization is covered by increased oxygen extraction,
      resulting in marked mixed venous oxygen desaturation. These physiological changes
      during postoperative mobilization were also seen in CABG patients. The
      mobilization pattern was also maintained on the second day after surgery. No
      serious side effects were observed in the controlled trials of mobilization of
      AVR patients after cardiac surgery. Over a 13-year period, we have mobilized more
      than 1200 AVR patients. No serious situations have occurred during or in direct
      connection to mobilization.

PMID- 17029178
TI  - Isthmus endoprosthesis stent-graft treatment: implantation of relay dedicated
      device.
AB  - Among the 123 patients treated in our department by endovascular stent graft, 113
      (91.8%) were identified as having involvement of the isthmus. Therefore, the
      incorrectly defined descending aortic disease is essentially a pathology of the
      isthmus that represents the distal portion of the arch. The key to the treatment
      of all types of aortic lesions rests on understanding the morphology of this
      region gifted with a "double S" configuration. Current thoracic devices are
      noncompliant systems and should be modified greatly, taking into account that the
      media of the aorta has a semi-compliant behavior. The resultant of power
      transmission is oriented at 45 degrees and produces a transmural radial force
      that animal implantation has demonstrated to be a torsional movement. The
      improvements in new devices actually result in a new generation of endoprostheses
      that seem to be closely related to the anatomy of the patient by increasing the
      conformability and, therefore, we expect an increase in durability. To test these
      features, we have studied a new stent graft in different settings of thoracic
      aortic disease. The new device should conform to current standards while
      simultaneously transmitting torsional forces. The dedicated delivery system
      should be arch-compatible, flexible but sufficiently rigid, and able to be three
      dimensionally oriented. Moreover, the new stent graft should follow the three
      dimensional anatomy of the "double S" configuration of the isthmus area and thus
      reduce the mismatch between the aorta and the device itself.

PMID- 17029179
TI  - Use of modular large femoral heads without liners in hip arthroplasty.
AB  - The use of large-diameter femoral heads in total hip arthroplasty appears to
      reduce the risk for dislocation, and potentially improve articular wear.
      Moreover, large-diameter total hip femoral heads have been determined to increase
      range of motion. The purpose of this study was to report our experiences with
      this new device. In our patient cohort, many patients have done extremely well in
      the short-term with this new device, and it seems these patients function better
      than those with a standard total hip arthroplasty. The patients who experience
      less pain are able to return to full activities postoperatively. The preliminary
      results of this study are encouraging, and large femoral head prosthesis appears
      to be a great choice for orthopaedic surgeons in primary total hip arthroplasty.

PMID- 17029180
TI  - Manipulation with prolonged epidural analgesia for treatment of TKA complicated
      by arthrofibrosis.
AB  - Inability to achieve adequate range of motion (ROM) after total knee arthroplasty
      (TKA) represents a frustrating complication for both patient and surgeon.
      Manipulation under anesthesia is indicated in TKA having less than 90 degrees ROM
      after six weeks, with no progression or regression in ROM. A modified technique
      has evolved for patients with chronic regional pain syndrome (CRPS) symptoms or
      persistent stiffness after standard manipulation. A retrospective review was
      conducted to determine the efficacy of the modified technique, which uses
      epidural anesthesia continued for postoperative analgesia, hospital stay of one
      to three days, continuous passive motion (CPM) for two to three days, and daily
      physical therapy (PT). Between 1997 and 2003, 5714 TKAs were performed in 4106
      patients. Manipulation using a standard technique was performed on 334 (5.8%)
      knees in 273 patients. Manipulation using a modified technique was performed on
      65 (1%) knees in 60 patients. Age averaged 58 years and body mass index (BMI)
      averaged 34.39. Follow up averaged 18.4 months. ROM improved significantly from
      71 degrees to 102 degrees (p < 0.0001). Knee Society pain, function, and total
      clinical scores all improved significantly (all p < 0.0001). Successful results
      were observed in 48 (74%) knees. Four (6%) additional knees achieved a successful
      result after a subsequent manipulation. Nine (14%) knees required component
      revision for treatment of persistent arthrofibrosis, which included one full
      revision, five polyethylene exchanges, and three revisions of femoral component
      and polyethylene. Two significant complications occurred: one subdural hematoma
      and one death due to pulmonary embolism. Although not without complications,
      manipulation under epidural anesthesia represents a viable option for treatment
      of persistent stiffness after TKA; 80% of these difficult cases achieved
      successful results.

PMID- 17029181
TI  - Pulsed electrical stimulation in patients with osteoarthritis of the knee: follow
      up in 288 patients who had failed non-operative therapy.
AB  - BACKGROUND: Optimized pulsed electrical stimulation (PES) regulates chondrocyte
      genes, enhances production of cartilage matrix materials, and inhibits production
      of matrix catabolic factors. METHODS: This prospective, cohort study examined the
      use of a PES device in treatment of knee osteoarthritis (OA) in patients who had
      failed non-operative therapy. Primary outcome measures were patient and physician
      global evaluation, and patient assessment of knee pain. RESULTS: This study
      included 288 (95 men, 193 women) patients who used the device from 16 to more
      than 600 days (mean: 889 hours). Improvement in all efficacy variables (p <
      0.001) occurred. A dose-response relationship between effect size and hours of
      usage was observed as cumulative time increased to more than 750 hours.
      Improvement in patient or physician global occurred in 59.0% of patients who used
      it less than 750 hours, and for 73.0% of those who used it more than 750 hours.
      An economic analysis of a sub-group of patients showed that 45.3% reduced
      nonsteroidal anti-inflammatory drug (NSAID) use by 50.0% or more. CONCLUSIONS: A
      highly optimized PES device successfully attenuated knee OA symptoms in patients
      who had failed non-surgical therapy. Less than 250 hours of therapy provided
      relief, but improvement increased in a dose-response manner after 750 hours of
      cumulative use.

PMID- 17029182
TI  - Endoscopic assisted lumbar microdecompressive spinal surgery with a new SMART
      endoscopic spine system.
AB  - In response to the rapid development and demand of outpatient endoscopic
      minimally invasive lumbar surgical technique, the SMART endoscopic spine system
      was developed for neurodecompression. This lumbar spine surgery is performed with
      a small skin incision, dilatation surgical technology, and an endoscopic-assisted
      spinal surgical system with progressive serial tubular retractors providing
      superior lighting and better visualization of the operative field for performing
      minimally invasive spinal surgery (MISS). The SMART system incorporates the
      advantages of posterior paramedian endoscopic assisted microdecompressive
      surgical spinal system and posterolateral endoscopic lumbar system. This
      versatile SMART endoscopic spine system with various sized working channels
      provides a generous and optimal access for endoscopic MISS of microdecompression
      of herniated lumbar disc, degenerative spinal disease, spinal stenosis, and
      removal of intraspinal lesions as well as creating an access for spinal
      arthroplasty and spinal fixation. With the unique features of the SMART system,
      the surgeon can take advantage of microscopic, endoscopic, or direct vision for
      microdecompressive spinal surgery, bridging endoscopic and conventional spinal
      surgery. It appears easy, safe, and efficacious. This less traumatic and easier
      outpatient MISS treatment leads to excellent result speedier recovery, and
      significant economic savings. The SMART endoscopic spine system, surgical
      indications, operative techniques, and the potential complications and their
      avoidance are described and discussed herein.

PMID- 17029183
TI  - In-vivo endoscopic visualization of patho-anatomy in painful degenerative
      conditions of the lumbar spine.
AB  - The degenerative processes in an aging spine have been defined traditionally only
      by our knowledge of the biology of disc and facet degeneration, as well as
      interpretation of post-mortem cryosections by forensic anatomist Wolfgang
      Rauschning, M.D. In this chapter, visualization of in-vivo patho-anatomy in a
      degenerating disc and spinal segment is demonstrated at surgery using the Yeung
      Endoscopic Spine System (Y.E.S.S.), (Richard Wolf Surgical Instrument Company,
      Vernon Hills, IL, USA). An Institutional Review Board (IRB)-approved study of
      endoscopic treatment for degenerative conditions of the lumbar spine incorporated
      intraoperative probing under local anesthesia and endoscopic treatment of the
      visualized patho-anatomy. An intraoperative evocative chromo-discogram, using
      indigocarmine, was used to elicit discogenic pain and label the fissured and
      degenerative nucleus pulposus for surgical removal and thermal modulation.
      Painful patho-anatomy was probed in a conscious patient. The most common
      endoscopic finding was Inflammatory tissue in the disc and annulus. Inflammation
      was correlated with the presence of annular tears. Patho-physiologic changes that
      affect the exiting nerve, which contains the Dorsal Root Ganglion (DRG), was
      associated with stenotic and chemical irritation. Unavoidable postoperative
      dysesthesia was associated with the presence of an inflammatory membrane, and
      removal or thermal coagulation of "anomalous" furcal nerves in the foramen that
      branched off of the exiting spinal nerve. Neo-angiogenesis and neurogenesis in
      the inflammatory membrane present in the foraminal triangle was a new finding not
      reported in traditional clinical studies. Visualization and treatment of
      pathologic findings inside (annular tears) and outside the disc in Herniated
      Nucleus Pulposus (HNP), synovial cysts, foraminal stenosis, central stenosis,
      spondylolisthesis, is demonstrated. The endoscopic foraminal approach to the
      spine and disc is a technique that provides access to patho-anatomy in the lumbar
      spine not usually feasible with traditional surgical methods. Favorable surgical
      results allow for continued evolution of the endoscopic method, concomitant with
      the continued evolution of endoscopic spinal surgery.

PMID- 17029184
TI  - Posterolateral spinal cord decompression in patients with metastasis: an
      endoscopic assisted approach.
AB  - Spinal tumors that are radioresistant or cause bony compression of the spinal
      cord often require surgical decompression to protect or restore neurological
      function. Metastatic lesions and primary tumors such as multiple myeloma usually
      arise in the vertebral body, which can collapse and become unstable, and can
      compress the anterior columns of the cord. Laminectomy is often ineffective in
      these patients, and direct anterior decompression through thoracotomy is the
      widely-accepted solution to the neurological problem. The anterior surgical
      approach is particularly challenging in the upper thoracic spine. Patients with
      limited pulmonary reserve due to pneumonectomy or pulmonary metastasis might not
      tolerate the loss of lung capacity necessitated by either thoracotomy or
      thoracoscopy. Because posterior instrumentation is usually needed to provide
      stability following corpectomy and spinal cord decompression, posterolateral
      approaches to spinal cord decompression have gained favor in recent years.
      Posterolateral decompression offers advantages over the combined anterior and
      posterior approach, reducing operative time, morbidity, and hospital stay.
      Drawbacks to traditional posterolateral decompressions include poor visualization
      of the tumor immediately anterior to the spinal cord and the need to manipulate
      the spinal cord to completely remove a tumor adherent to the dura. Endoscopically
      assisted posterolateral decompression allows decompression of the anterior
      surface of the spinal cord, the point of pressure in most circumstances.
      Endoscopic video assistance facilitates vertebrectomy, cord decompression, and
      anterior reconstruction, all performed through the same posterior incision.
      Endoscopic assisted spinal cord decompression dramatically reduces morbidity, ICU
      requirements, and inpatient hospitalization and has proven useful for a variety
      of metastatic tumors at every level of the spinal column.

PMID- 17029185
TI  - Interspinous process decompression (IPD) system (X-STOP) for the treatment of
      lumbar spinal stenosis.
AB  - With increased life expectancy and an aging population, many patients suffering
      from progressive lumbar spinal stenosis with symptomatic neurogenic intermittent
      claudication (NIC) have been limited to a choice between nonsurgical therapies or
      a more traumatic decompressive surgical procedure, with or without lumbar fusion.
      The interspinous process decompression (IPD) system, the X-STOP implant, was
      developed to provide a minimally invasive alternative therapeutic treatment of
      lumbar spinal stenosis. The X-STOP IPD system, surgical indications, operative
      techniques, and the potential complications and their avoidance are described and
      discussed herein.

PMID- 17029186
TI  - Intradural lysis and peripheral nerve implantation for traumatic obsolete
      incomplete paralysis.
AB  - Twenty-eight patients who suffered traumatic obsolete incomplete paralysis were
      treated with intradural lysis and peripheral nerve implantation by a microsurgery
      technique. The endorachis was opened and the fibrous bands adhering to the spinal
      cord from the arachnoid, pia mater spinalis, ligamenta denticulatum, and the
      initial part of the nerve root were completely relieved. The abnormal spinal cord
      was then opened by three to six incisions, which were each 0.1 mm to 0.2 mm deep
      and longer than the abnormal portion. A cyst found in the back or side of the
      spinal cord was opened and the liquid in it was drained. After that, the denuded
      spineurium and perineurium of the autogenous sural nerve were grafted, which
      makes the character and aspect of the nerve like the cauda equine. The nerve was
      longitudinally implanted into the incised spinal cord, and the cyst was waded
      with grafted nerve and at least one of them is ectropion sutured with the pia
      mater with 9-0 scatheless wire as a drain. Finally, the endorachis was covered by
      sacrospinal muscle flap. These patients were followed for 2 years to 8 years
      (average 3.5 years), and the sensibility and motion of each increased at least
      one grade. The strength of the main muscle was increased two grades and reached
      four grades in 11 patients, and the capability to walk was recovered. Relieving
      of the adhesion in the endorhachis, carving the cicatricial spinal cord, and
      implanting the autogenous peripheral nerve yields good results by initial
      clinical observation for traumatic obsolete and incomplete paralysis.

PMID- 17029187
TI  - Treatment of osteochondral lesions of the talus with cryopreserved talar
      allograft and ankle distraction with external fixation.
AB  - This article presents the results of a retrospective review of six osteochondral
      lesions on six patients (five men and one woman) treated with transplantation of
      cryopreserved talar allograft and ankle joint distraction. All patients
      complained of ankle pain existing for a long time secondary to a traumatic
      episode confirmed through MRI. Lesions ranged in measurement from 0.8 cm x 0.8 cm
      to 3.2 cm x 1.8 cm with an average size of 2.1 cm x 1.5 cm. Each patient
      underwent talar dome transplantation using fresh frozen talar allograft followed
      by ankle distraction. Distraction was obtained using a three-ring multiplanar
      external fixation device. All surgeries were performed between 2002 and 2004. All
      external fixators were removed at 8 weeks and patients remained partial-weight
      bearing in a removable cast boot for an additional 8 weeks. Serial postoperative
      radiographs showed complete consolidation of the allograft within 16 weeks. The
      average follow up time was 24 months, and all patients related a subjective
      decrease in symptoms and increase in activity levels. Patients were also
      evaluated utilizing the Maryland Foot Score both pre- and postoperatively.
      Preoperatively, four patients were graded as fair and two were graded as poor.
      Postoperatively, two patients related excellent results, three patients related
      good results, and one patient related fair results. Several patients experienced
      minor complications such as pin site irritation (five patients), painful talar
      wire (one patient), and periostitis (one patient). No patients experienced any
      major complications and none have required additional surgery. We feel that these
      initial results warrant further investigation of this treatment.

PMID- 17029188
TI  - Alloplastic reconstruction of the temporomandibular joint in treatment of
      craniofacial developmental or congenital anomalies: a surgical case report.
AB  - OBJECTIVE: To describe the surgical planning and treatment approach in addressing
      the oral and maxillofacial needs for one particular patient suffering congenital
      anomalies of the craniofacial anatomy. A secondary objective is to restore
      mandibular and maxillary function and esthetics to the young, adult patient. The
      tertiary objective is to educate the surgeon as to alloplastic implant options
      that may be available to restore function and relieve pain for the patient
      missing certain anatomical structures from birth. METHODS: Through the use of
      advanced medical imaging tools, a thorough understanding of the patient's prior
      failed medical treatments, and a meticulous understanding of the benefits of
      alloplastic reconstruction, the surgeon can mitigate patient symptoms and at the
      same time increase the probability of a successful outcome. The surgeon can then
      collaborate with the surgical and implant design team to not only prescribe the
      surgical correction necessary, but also design and construct the actual
      temporomandibular joint (TMJ) and mandibular implants used for the case, as well
      as perform mock surgery on a stereolithography anatomical (SLA) model needed to
      restore function and esthetics for the patient. The end result is that a Patient
      Specific (custom) (TMJ Implants, Inc., Golden, CO, USA) prosthesis can then be
      manufactured and adapted surgically to the patient's unique anatomy. RESULTS: The
      early results from this alloplastic reconstructive surgery have brought forth the
      anticipated results of replacement of the congenitally absent TMJ, improvement of
      jaw function, reduction of joint pain, as well as improvement of the esthetics.
      Without this breakthrough surgical development, many of these congenital
      anatomically deficient patients would not be able to enjoy normal breathing,
      mastication, jaw function, esthetics, oral and dental health, and the emotional
      relief that these corrections allow. CONCLUSIONS: Many patients who suffer birth
      related anatomical deficiencies (such as cleft lip and branchial arch syndrome)
      never receive the surgical correction necessary. Many have had autogenous
      reconstruction of missing mandibular and TMJ structures only to relapse, at
      times, into a more disfiguring and lasting condition. By simply placing a
      Christensen Fossa-Eminence Prosthesis (FEP) and Condylar Prosthesis (CP) in a
      total joint-replacement solution, one is more likely to achieve satisfactory TMJ
      mobility and reduction in pain, as well as the mechanical replacement of missing
      anatomical structures and predictable and lasting improvement. As an additional
      benefit, the patient also would enjoy enhanced esthetics.

PMID- 17029189
TI  - Principles of microneurosurgery for safe and fast surgery.
AB  - Since their introduction by Prof. Yasargil in the 1960s, Microneurosurgical
      techniques have been the essentials of neurosurgical practice. Principles of
      Microneurosurgery are mainly based upon handling the lesions of different
      characteristics that can be localized in any part of the nervous system. Whereas
      the aim is to treat these lesions with efficacy and precision, the performance
      should be non-traumatic and minimally invasive. Delicate movements of instruments
      under the magnification of an operating microscope require a good knowledge of
      Microneurosurgical anatomy and experience. Professional teamwork is the essential
      part of Microneurosurgical operations. Fascinating approaches are not practical
      unless combined with appropriate positioning and optimal conduction of
      Neuroanesthesia. Although the neurosurgical operations are highly dependent on
      technological advancements, their use should be adjusted according to personal
      preferences and financial resources. To keep the operations simple and fast, and
      appreciate normal anatomy, only a limited array of instruments is preferable for
      use. The basic principles of Microneurosurgery discussed in this chapter are
      based on the Helsinki and Kuopio Neurosurgery practices in Finland, as well as
      the Senior Author's (J.H.) experience in approximately 10,000 microsurgery
      operations. The question to be addressed is: How does one perform operations
      safer and faster while preserving the normal anatomy?

PMID- 17029190
TI  - Local infusion therapy in the monkey brainstem: technical considerations.
AB  - This chapter assesses the safety of freehand placement of an infusion catheter
      (outer diameter, 0.3 mm) in brainstems of cynomolgus monkeys (Macaca
      fascicularis) for local infusion therapy. A posterior midline approach through
      the cerebellum and roof of the fourth ventricle was used to implant catheters
      into a pontine target area. Computer tomography (CT), magnetic resonance imaging
      (MRI), and histology were used to examine the position of the implants. The
      freehand placement of a catheter resulted in approximately 5-mm variations in
      anterior-posterior and dorsal-ventral locations of the targeted implantation
      site. No evidence of morbidity from the surgery, or from the infusion process was
      present. In conclusion, small-diameter catheters for chronic drug infusions can
      be implanted safely into the brainstem, an eloquent region that has been
      considered surgically inoperable. Infusion systems may offer a minimally
      invasive, generally applicable tool to provide chronic therapy for central
      nervous system (CNS) lesions.

PMID- 17029191
TI  - The G401D mutation of OPA1 causes autosomal dominant optic atrophy and hearing
      loss in a Chinese family.
AB  - OBJECTIVE: To describe the clinical and genetic characteristics of a Chinese
      family affected with optic atrophy 1 (OPA1). METHODS: Linkage analysis and DNA
      sequencing as well as PCR/restriction fragment length polymorphism (RFLP)
      analysis were performed to identify the disease-causing mutation. RESULTS: A
      missense mutation, G401D in the OPA1 gene was identified, and the patients
      demonstrate inherited syndrome of optic atrophy and hearing loss. CONCLUSION: The
      present study demonstrates that a mutation in the OPA1 gene can cause optic
      atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead
      to OPA1 combined with hearing loss.

PMID- 17029192
TI  - [Study on the molecular background of Del phenotype in Chinese population].
AB  - OBJECTIVE: To elucidate the molecular background of Del phenotype in the Chinese
      population and explore new Del alleles. METHODS: Five hundred and fifteen RhD
      negative blood samples was tested by Rh typing test, indirect antiglobulin test
      and adsorption and elution assay to screen the Del phenotype. DNA of all the Del
      samples was analysed by multiplex polymerase chain reaction (MPX PCR) for the
      presence of RHD and by sequence-specific primer polymerase chain reaction (PCR
      SSP) for Del alleles: RHD 1227A and RHD 885T. Samples which showed the negative
      result by PCR-SSP, were additionally analysed by genomic DNA sequencing and cDNA
      sequencing. RESULTS: Seventy-nine Del samples were found by adsorption and
      elution assay. All these samples had RHD exons 3, 4, 5, 6, 7 and 9. Except 4 Del
      samples, other 75 Del samples carried the RHD 1227A allele. None of the samples
      had the RHD 885T allele. Four novel RHD alleles were found in these four Del
      sample. There were RHD 3G-->A (GenBank DQ310735), RHD 28C-->T, RHD 53T-->C
      (GenBank DQ451877,DQ451878), RHD 251T-->C (GenBank DQ310734). CONCLUSION: fnRh
      blood group system is very complex. New D variation phenotypes and new RHD
      alleles may be discovered ceaselessly.

PMID- 17029193
TI  - [Functional interaction of the C-terminal of Nogo protein with connexin 26 and
      the expression of Nogo's mRNA in the murine inner ear].
AB  - OBJECTIVE: To screen and identify the proteins that interact with connexin 26
      (CX26) and to analyze the expressions of these proteins in cochlea so as to
      explore the proteins that relate to the trafficking, assembly, localizing and gap
      junction functions of CX26. METHODS: The whole coding region of GJB2 (CX26) gene
      was amplified from normal human genomic DNA by polymerase chain reaction (PCR)
      and then directionally subcloned into the vector pGBKT7 plasmid of the Match
      Maker Ga14 Two-Hybrid System 3 as a target to screen the interactive proteins of
      CX26 from the human fetal brain cDNA library by the yeast two hybrid technique.
      The false positive clones were discarded from the preys by repeated yeast two
      hybrid method between CX26 and everyone of the preys respectively. The DNAs of
      the insert of the identified positive clone were sequenced and BLAST analyzed
      against the GenBank. Lastly, the mRNA of the gene encoding the identified protein
      was analyzed in the murine inner ear by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: The insert of one positive clone contained 867 bp
      with the former 525 bp being coding region. The DNA sequence and the open reading
      frame of the insert were identical to the 525 bp before the stop codes (including
      the stop codes) and the 238 bp after the stop codes of RTN4 gene which encoded
      Nogo protein. And the 174 amino acid residues encoded by the insert were those of
      the C-terminal of Nogo protein: Nogo-A, Nogo-B and Nogo-C. RTN4 mRNA expressed in
      the murine inner ear was confirmed by RT-PCR method. CONCLUSION: The C-terminal
      of Nogo protein interacts with CX26. Nogo protein expresses in the inner ear and
      may take part in the trafficking of CX26 or CX26 gap junction function.

PMID- 17029194
TI  - [Characteristics of IGF-II gene imprinting in twin placentas].
AB  - OBJECTIVE: To compare insulin-like growth factor II (IGF-II) gene imprinting in
      twin placentas with singleton ones and to determine whether imprinting was
      influenced by assisted reproductive technology, zygosity and fetal sex. METHODS:
      One hundred and sixty cases of twin placentas and 42 cases of singleton ones were
      recruited. Allele-specific IGF-II expression was determined by reverse
      transcription-PCR combined with analysis of an Apa I-sensitive restriction
      fragment length polymorphism. RESULTS: Although the incidence of IGF-II
      imprinting loss was higher in normal twin placentas than in singleton ones (20.6%
      vs 8.7%), there was no statistical significance. There were no significant
      differences between twins conceived by assisted reproductive technology and those
      conceived spontaneously (17.9% vs 24.4%), and between dizygotic and monozygotic
      twins (22.4% vs 16.7%). The incidence of IGF-II imprinting loss in placenta of
      female twins was statistically higher than that of male ones (26.4% vs 9.8%).
      CONCLUSION: The risk of IGF-II gene imprinting loss is higher in female twins and
      has no relationship with assisted reproductive technology and zygosity.

PMID- 17029195
TI  - [A mutation in TGF beta1 gene encoding the latency-associated peptide in a
      Chinese patient with Camurati-Engelmann disease].
AB  - OBJECTIVE: To identify the mutation in transforming growth factor-beta1 gene (TGF
      beta1) in a Chinese patient with Camurati-Engelmann disease(CED). METHODS:
      Denaturing high-performance liquid chromatography (DHPLC) analysis was performed
      on the whole seven coding exons and exon-intron boundaries, then the mutation was
      identified by direct sequencing. RESULTS: Mutation screening of TGF beta1 in this
      patient revealed a heterozygous missense mutation R218H in exon 4. CONCLUSION:
      The identification of the mutation could provide essential data for subsequent
      therapy and genetic counseling.

PMID- 17029196
TI  - [Analysis of differential expression genes related to different metastasis
      potential of adenoid cystic carcinoma using restriction fragments differential
      display PCR].
AB  - OBJECTIVE: To construct differential expression profiles of adenoid cystic
      carcinoma cell lines for screening candidate genes related to metastasis and to
      verify some candidate genes in adenoid cystic carcinoma. METHODS: Restriction
      fragments differential display PCR (RFDD-PCR) was used to set up gene expression
      profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and
      low metastasis potential respectively. Candidate genes were screened through
      bioinformatics analysis. Then, a gene family of these candidate genes was checked
      using semi-quantitative reverse transcription-PCR(RT-PCR). RESULTS: Two gene
      expression profiles including 5420 gene fragments were constructed, 12 genes of a
      family called matrix metalloproteinase genes (MMPs) were observed obvious
      differentially expressed between two cell lines. Results of semi-quantitative RT
      PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and
      MMP24. CONCLUSION: The construction of gene expression profiles of ACC-M and ACC
      2 cell lines makes the foundation for seeking the target genes of adenoid cystic
      carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis,
      development and metastasis of adenoid cystic carcinoma, and different metastasis
      potential may result from different subtype of MMPs gene family.

PMID- 17029197
TI  - [Genetic heterogeneity for familial recurrent hydatidiform mole].
AB  - OBJECTIVE: To determine the parental origin of the genome in the molar
      pregnancies of two familes with familial recurrent hydatidiform mole (FRHM) and
      to investigate whether the gene responsible for FRHM is likely to be located
      within the 19q13.4 region in these familes. METHODS: The features of complete
      hydatidiform mole (CHM) were confirmed by pathological examination. DNA of CHM
      was prepared from sections of formalin-fixed paraffin-embedded blocks of molar
      tissue following laser capture microdissection. The polymerace chain reaction was
      used to amplify microsatellite polymorphisms in DNA from the patients, their
      husbands and the captured molar tissue. Parental contributions to the molar
      tissue were determined using ABI 310 GeneScan software. Genotyping and haplotype
      analysis of the candidate region on 19q13.4 was performed for members of both
      families using 25 microsatellite markers. RESULTS: One CHM from each family was
      identified as a biparental complete hydatidiform mole. All patients were
      heterozygous for most of the markers in the chromosome region of interest. In
      addition the two affected sisters in one of the families had different genotypes
      for the 19q13.4 region, suggesting that mutations in a different locus might be
      responsible for the disorder in this family. CONCLUSION: The location of the gene
      responsible for FRHM is unlikely to be located in the 19q13.4 chromosomal region
      in these two families suggesting that FRHM shows genetic heterogeneity.

PMID- 17029198
TI  - [Identification of two novel mutations of human blood coagulation factor V gene
      in a Chinese family with congenital factor V deficiency].
AB  - OBJECTIVE: To discover the mutations of human blood coagulation factor V (FV)
      gene in a Chinese family with congenital factor V deficiency, and to explore the
      molecular mechanism associated with the congenital factor V deficiency. METHODS:
      PCR and DNA sequencing were used to look for the FV gene mutations in the
      proband. And the novel mutation were testified by PCR restriction fragment length
      polymorphism technique or reverse DNA sequencing. One hundred healthy volunteers
      were chosen as controls at random. RESULTS: Two novel mutations were discovered
      in the FV gene of proband, which were the A1763C missense mutation in exon 11 and
      the splicing site mutation in the 3' terminal of intron 16 (G-->T). The pedigree
      analysis showed that the two mutations inherited from his parents respectively:
      the A1763C came from his father, and the G-->T from his mother. The A1763C
      missense mutation in exon 11 was not found in each of 100 healthy volunteers.
      CONCLUSION: The congenital deficiency of FV in the proband might be caused by the
      A1763C missense mutation in exon 11 and the splicing site mutation in the 3'
      terminal of intron 16, which jointly caused the proband to be a double
      heterozygote.

PMID- 17029199
TI  - [Associations between Ser447Ter gene polymorphism of lipoprotein lipase and
      atherosclerotic cerebral infarction].
AB  - OBJECTIVE: To investigate the relationship between lipoprotein lipase (LPL) gene
      Ser447Ter polymorphism and atherosclerotic cerebral infarction (CI), and to
      investigate the effect of Ser447Ter polymorphism on plasma lipids, carotid intima
      media thickness (IMT) and carotid artery plaque (CAP) in patients with CI.
      METHODS: PCR-restriction fragment lengh polymorphism (PCR-RFLP) technique was
      used to detect LPL gene Ser447Ter polymorphism in 166 patients with CI (CI group)
      and 72 healthy subjects (control group). Carotid IMT and CAP were measured with
      carotid color ultrasonographic doppler for the patients and the controls.
      RESULTS: CG+GG carriers had lower plasma triglyceride (TG) levels and higher high
      density lipoprotein cholesterol (HDL-C) levels than CC carriers in CI group
      (P=0.001 and P=0.007 respectively). CG+GG carriers had lower plasma TG levels
      than CC carriers in control group (P=0.041). The frequency of G allele in CI
      patients was significantly lower than that in control subjects (P= 0.014). There
      was no statistical correlation between LPL Ser447Ter gene polymorphism and
      carotid IMT and CAP. CONCLUSION: The Ser447Terls polymorphism of LPL gene is
      significantly associated with plasma lipids and CI. G allele genotype may lead to
      decrease of plasma TG and increase of plasma HDL-C. G allele may be a protective
      genotype of CI.

PMID- 17029200
TI  - [Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity
      and controls in Uighur nationality].
AB  - OBJECTIVE: To investigate the association of polymorphisms in the apolipoprotein
      B gene (APOB) 3'variable number of tandem repeat with natural longevity in the
      Xinjiang Uighur nationality people. METHODS: Totally 191 healthy individuals over
      90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur
      population, the nationality, gender and living area were matched. Genotyping was
      performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and
      PCR-sequencing. RESULTS: Fourteen alleles were found in the Xinjiang Uighur
      nationality population. The frequency of HVE36 and HVE42 in the natural longevity
      group were significantly higher than that in the control group (both P<0.05) and
      HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group.
      However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the
      natural longevity group compared to the control group. Logistic regression
      analyses revealed that allele L and the genotypes LL were positively associated
      with age, whereas the allele S and genotype SS were negatively associated with
      age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by
      PCR-sequencing. CONCLUSION: These results indicate that the S allele, and SS
      genotype are frail factors in China Uighur natural longevity people, whereas
      allele L and genotypes LL are protective factors.

PMID- 17029201
TI  - [Genetic polymorphism of HLA-Cw locus in hematopoietic stem cell transplantation
      patient and donor population].
AB  - OBJECTIVE: To analyze the distribution of genes in HLA-Cw locus from Han
      population of China in a large scale, and to provide basic data for further study
      on the genetic characteristics of HLA-Cw locus of this population. METHODS:
      Totally 1285 unrelated Chinese Han individuals were typed by PCR-SSP, and
      statistics was utilized to investigate the distribution rules of detected genes.
      RESULTS: Twenty-three HLA-Cw alleles were identified in Chinese Han population,
      out of them HLA-Cw*01, *03, *07 and *08 were the commonest genes, which accounted
      for frequencies of 0.1529, 0.2385, 0.1747 and 0.1004, respectively. Five genes
      which could not be identified by serological method were deaed: HLA-Cw*12, *14,
      *15, *16 and *17. Hardy-Weinberg test showed that the observed genetic
      polymorphism distribution values were correspondent with the expected (chi
      square=73.74, df=98, P>0.5). CONCLUSION: This study may serve a full-scale
      scientific genetic parameters of HLA-Cw genes for Chinese Han population studies.

PMID- 17029202
TI  - [Association between depression and G72 gene polymorphism].
AB  - OBJECTIVE: To investigate the association between G72 gene polymorphisms and
      depression,and to probe the difference of G72 gene polymorphisms between
      depression with and without mixed family history. METHODS: The polymorphisms of
      G72 gene (rs947267 and rs2181953) were detected by PCR technique in 100
      depressive patients without mixed family history, 50 depressive patients with
      mixed family history and 86 normal controls. RESULTS: (1) The frequencies of
      rs947267 genotypes and alleles in female depressive patients without mixed family
      history were significant different to the controls (P=0.017 and P=0.008), the OR
      scores were 0.300 (A/A, P=0.010), 0.456(A, P=0.008) and 2.195(C, P=0.008)
      respectively; but in male patients there were no significant differences to the
      controls (P>0.05). (2) The frequencies of rs2181953 genotypes and alleles in the
      depressive patients without mixed family history were not significantly different
      to the controls regardless of sex (P>0.05). (3) The frequencies of rs947267 and
      rs2181953 genotypes and alleles in the depressive patients with mixed family
      history were not significantly different to the controls regardless of sex
      (P>0.05). CONCLUSION: The G72 gene polymorphism may be associated with female
      depressive patients without mixed family history,C allele of rs947267 may be the
      risk factor.

PMID- 17029203
TI  - [Investigation of RHD 1227A allele in five pedigrees in Zhejiang Han population].
AB  - OBJECTIVE: To analysis the genetic mode of Rh DEL phenotype and RHD 1227A allele
      in Zhejiang Han population through family investigations. METHODS: Rh DEL
      phenotypes were identified by a serologic adsorption-elution method. Two
      polymerase chain reaction-sequence specific prime (PCR-SSP) methods which
      detectED RHD 1227A allele and Rhesus hybrid box, respectively, and a nucleotide
      sequencing method focused on the exon 9 of RHD 1227A allele were employed to
      determine the zygosity of RHD allele. RESULTS: All five probands with Rh DEL
      phenotype harbored a RHD 1227A allele and had a RHD allele deletion, and they
      were RHD 1227A/RHd heterozygote. One of the parent members was found to contain a
      RHD 1227A allele and a normal RHD allele in pedigree 1, 2 and 3, respectively.
      Thus, they were RHD 1227A/RHD heterozygotes and presented normal D positive
      phenotype. The son of proband No 1. inherited the RHD 1227A allele and presented
      a normal D positive phenotype due to a RHD 1227A/RHD heterozygote; The offsprings
      of proband No. 2, No. 4, and No. 5 did not inherit RHD 1227A allele and presented
      a normal D positive phenotype. CONCLUSION: RHD 1227A allele is an important
      genetic marker of Rh DEL phenotype; RHD 1227A is recessive to normal RHD allele
      and dominant to RHd allele; RHD 1227A allele is an ancestral, but not a
      spontaneously mutated allele.

PMID- 17029204
TI  - [The investigation of the technology of microcell mediated chromosome transfer
      for functional localization of metastasis suppressor genes for liver cancer on
      human chromosomes].
AB  - OBJECTIVE: In order to seek the functional evidence that there could be
      metastatsis suppressor gene for liver cancer on human chromosomes, the objective
      of this study is to establish a method of microcell mediated chromosome transfer
      (MMCT). METHODS: Human chromosome 8 randomly marked with neo gene was introduced
      into highly metastatic rat liver cancer C5F cell line by treating the single
      human chromosome donor cells with sequential steps of micronucleation,
      enucleation and microcell fusion. Double selections of G418 and HAT were applied
      to screen positive microcell hybrids, which were cloned by single cell isolation.
      Microcell hybrid clones were confirmed by STS-PCR and WCP-FISH. RESULTS:
      Microcell hybrids resistant to HAT and G418 were obtained, from which 15 clones
      were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that
      human chromosome 8 had been successfully introduced into rat liver cancer cell
      line C5F. The human chromosome 8 introduced into C5F was found to have random
      loss of chromosome fragments by STS-PCR and consistent recombination with rat
      chromosome by WCP-FISH. CONCLUSION: The successfulls introduction of human
      chromosome into highly metastatic rat liver cancer cell line has established the
      technical basis for functional localization of metastasis suppressor gene(s) for
      liver cancer on human chromosomes.

PMID- 17029205
TI  - The association of polymorphisms of CDT1 and GMNN gene with the risk of breast
      cancer in Chinese women: a case-control analysis.
AB  - OBJECTIVE: To investigate the association of polymorphisms of CDT1 and GMNN gene,
      two important genes participating in DNA replication, with the risk of sporadic
      breast cancer. METHODS: Using polymerase chain reaction-restriction fragment
      length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis
      (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a
      case-control study of 427 breast cancer cases and 477 cancer-free controls in a
      Chinese population. RESULTS: No significant association of the CDT1 838G/A and
      GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted
      OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95%
      CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a
      significant association of CDT1 GA+AA genotypes with breast cancer risk among
      subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20
      4.09). CONCLUSION: These findings suggest that the CDT1 838G/A and GMNN 387C/A
      polymorphisms may not play a major role in the etiology of breast cancer, but
      CDT1 variant may have a potential role only in genetically susceptible women.

PMID- 17029206
TI  - [Association of the polymorphism of macrophage migration inhibitory factor gene
      with coronary heart disease in Chinese population].
AB  - OBJECTIVE: Inflammation is involved in the process of coronary heart disease
      (CHD). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine
      which can inhibit the random migration of macrophages and concentrate macrophages
      at the inflammatory site, and is thought to play an important role in cell
      mediated immunity. The present study is to investigate the association of the 
      173 G/C polymorphism of MIF gene with the outcome of the CHD. METHODS: One
      hundred and thirty-eight patients with coronary angiography (CAG) proved CHD were
      studied, and 163 healthy matched controls in Guangdong were studied. Patients and
      controls were genotyped for a single nucleotide polymorphism in the 5'-flanking
      region at position -173 of the MIF gene, using PCR-RFLP analysis, followed by DNA
      sequencing identification. RESULTS: Only MIF -173G/G and MIF -173G/C genotypes
      were detected in CHD patients and controls. The MIF -173 G allele was detected in
      0.966 of normal controls and 0.917 of patients, while MIF -173 C allele was
      detected in 0.034 of normal controls and 0.083 of patients. Individuals
      possessing a MIF-173*C genotype have an increased risk of CHD (16.7% versus 6.8%)
      (OR: 2.764, 95% CI: 1.295-5.899; P= 0.007). CONCLUSION: These results suggest
      that MIF -173G /C polymorphism was associated with CHD in Chinese population, the
      MIF -173C allele might be a risk factor for CHD in Chinese Han nationality.

PMID- 17029207
TI  - [Association and mutation analysis of GLI3 gene in idiopathic congenital talipes
      equinovarus].
AB  - OBJECTIVE: To explore the association and mutation of GLI3 gene in idiopathic
      congenital talipes equinovarus(ICTEV). METHODS: (1) Genotype of 2 single
      nucleotide polymorphism (SNP) in 84 idiopathic congenital talipes equinovarus
      nuclear pedigree were analyzed by restriction fragment length polymorphism.
      Association analysis was directed between single SNP locus and ICTEV through ETDT
      software, respectively.(2) Mutation sites in exon 9,10,11,12 of GLI3 gene were
      detected in 103 patients with ICTEV by denaturing gradient gel electrophoresis
      technique. RESULTS: rs929387ls located in exon 14 of GLI3 gene have transmission
      disequilibrium in 84 nuclear pedigrees (P<0.05), and rs846266 located in exon 4
      have no transmission disequilibrium (P>0.05). A synonymous mutation in exon 9 was
      detected in one patient and his mother. CONCLUSION: There is an association
      between GLI3 gene and ICTEV, and exons 9,10,11,12 are not its mutation hot spots.

PMID- 17029208
TI  - [Association of genetic polymorphisms in human leukocyte antigen-DQA1 with
      intrahepatic cholestasis of pregnancy in Chengdu district].
AB  - OBJECTIVE: To explore the relationship between human leukocyte antigen-DQA1 (HLA
      DQA1) allele gene polymorphism and intrahepatic cholestasis of pregnancy (ICP).
      METHODS: Forty-five patients with ICP, eighteen ICP families, forty-five normal
      pregnant women and eighteen normal control families were tested for HLA-DQA1
      allele gene polymorphism by polymerase chain reaction with sequence-specific
      primer (PCR-SSP) method. RESULTS: The frequency of HLA-DQA1*0301 in normal
      pregnant women was markedly higher than that in the ICP group (P>0.05). No
      significant differences were observed between the frequencies of other detected
      HLA-DQA1 alleles in both groups. The analysis of feto-maternal or couples sharing
      of the HLA-DQA1 alleles showed that no significant differences were observed
      between the two groups. CONCLUSION: The above findings suggest that there is no
      significant association between the genetic polymorphisms in HLA-DQA1 and ICP in
      Chengdu district; HLA-DQA1*0301 may be a protective gene against ICP. It may
      prevent the development of ICP.

PMID- 17029209
TI  - [Avoiding the interference of ABCD1 pseudogenes in the molecular diagnosis of X
      linked adrenoleukodystrophy by double amplification refractory mutation system].
AB  - OBJECTIVE: To avoid the interference of ABCD1 pseudogenes, the amplification
      refractory mutation system (ARMS) was used to analyze the mutation of ABCD1 gene
      in the molecular diagnosis of X-linked adrenoleukodystrophy (ALD). METHODS: The
      upstream primers (wild primer and mutation primer) were designed according to the
      principle of primer-design in ARMS. In addition, a common downstream primer was
      designed in the same way to discriminate ABCD1 gene from its prologous
      pseudogenes. The genomic DNA isolated from the peripheral blood leukocytes of the
      family members and normal controls was amplified by PCR. RESULTS: In double ARMS,
      a specific product of 107bp could be amplified from genomic DNA of the patient
      with R617C mutation in ABCD1 gene and his mother, while the same product was not
      found when the genomic DNA of the patient's father and normal controls was used.
      Thus, the interference of ABCD1 pseudogenes in molecular diagnosis of ALD was
      excluded successfully at genomic DNA level. CONCLUSION: Double ARMS is a quick
      and effective method to eliminate the interference of the pseudogenes in
      detecting ABCD1 gene mutations.

PMID- 17029210
TI  - [Correlation between the polymorphism of platelet glycoprotein GPIb alpha Kozak
      gene and transient ischemic attack].
AB  - OBJECTIVE: Genic susceptibility could increase the risk of transient ischemic
      attack (TIA). The objective of this study is to investigate the relationship
      between the polymorphism of platelet glycoprotein GPIb alpha Kozak gene and TIA
      in Qindao Han population. METHODS: The polymorphisms of platelet glycoprotein
      GPIb alpha Kozak gene -5T/C in TIA patients and normal control were detected with
      sequence-specific primers polymerase chain reaction (PCR-SSP). RESULTS: The
      prevalence of the CC genotype and C alleles were significantly higher in TIA
      patients than in the control group (P<0.05). The positive correlation between C
      allele and TIA was showed by logistic regression analysis (P=0.016). CONCLUSION:
      The -5T/C polymorphism of the platelet glycoprotein GPIb alpha Kozak gene is
      implicated in the pathogenesis of TIA. C allele is an independent risk factor for
      TIA.

PMID- 17029211
TI  - [Methylation status of FHIT gene in plasma and expression of FHIT gene in cancer
      tissue of cervical cancer patients].
AB  - OBJECTIVE: To explore the methylation status of 5' CpG island of fragile
      histidine triad (FHIT) gene in plasma and the expression of FHIT protein in
      cancer tissue of cervical cancer patients. METHODS: Methylation-specific PCR (MS
      PCR) was employed to examine methylation of FHIT gene in 151 plasma samples
      before treatment. The immunohistochemistry was used to the expression of FHIT
      protein in cancer tissues. RESULTS: CpG island methylation of FHIT was detected
      in 31.13% of plasma samples. The expression of FHIT protein was decreased or
      discarded in 59.60% of cervical cancer tissues. Among them 47.78% was included in
      methylation positive samples. CONCLUSION: CpG island methylation of FHIT gene in
      plasma plays an important role on cervical cancer, which results in decreased
      expression of FHIT protein. It can be used to diagnose and evaluate the effect of
      treatment to cervical cancers.

PMID- 17029212
TI  - [Analysis of the non-Hodgkin lymphoma's clinic and blood marrow cytogenetics].
AB  - OBJECTIVE: To analyze the relationship among cytogenetics, hematopathology,
      morphology, clinic tumor index and prognosis of the non-Hodgkin lymphoma(NHL)
      patients. METHODS: Cytogenetics analysis of bone marrow cells was performed by
      direct method and 24 h culture method in 20 cases of NHL. Serous P53 protein was
      detected in all patients. RESULTS: Out of the twenty NHL patients, eight had bone
      marrow infiltration, and nine were found with abnormal karyotype: three were
      chromosome number abnormalities, one was t(14,18)(q32;q21), one was 14q+, two
      were t(8;14)(q24;q32), two were t(8;14)(q24;q32) with additional changes of
      chromosome. The serous P53 protein of patients with abnormal karyotype was
      significantly higher than that with normal karyotype. CONCLUSION: t(8;14)
      (q24;q32) is the most classic translocation in NHL, The patients with this
      karyotype have worse prognosis. The increase of mutant serous P53 relates to
      abnormal karyotype, and the patients with high mutant P53 level in serum also
      have worse prognosis.

PMID- 17029213
TI  - [The investigation and analysis of the Rh blood type distribution in four kinds
      of the minority nationalities (Miao, Buyi, Dong and Shui) in Guizhou, China].
AB  - OBJECTIVE: To comprehend the Rh blood type distribution and the gene frequency in
      four main kinds of the minority nationalities in Guizhou, China, so as to supply
      a scientific foundation for guiding the prevention and cure against the Rh
      hemolysis illness. METHODS: The irrelative individual blood of the four kinds of
      the minority nationalities (Miao, Buyi, Dong and Shui) in Guizhou was randomly
      collected in complete group style and the Rh blood type was identified and
      analyzed. RESULTS: Totally 15,992 minority nationality people were inspected and
      checked, and 4851 persons of Han nationality people were chosen as controls.
      Fifty-one persons were proven as Rh (D)negative individuals, in which, d gene
      frequency of Miao nationality population was 0.0474 and the Rh negative rate was
      0.22%, d gene frequency of Buyi nationality population was 0.0602 and the Rh
      negative rate was 0.36%, d gene frequency of Dong nationality population was
      0.0378 and the Rh negative rate was 0.14%, d gene frequency of Shui nationality
      population was 0.0307 and the Rh negative rate was 0.09%. d gene frequency of Han
      nationality population was 0.0574 and the Rh negative rate was 0.33%. In the four
      minority nationality populations, there was a common characteristic of the
      highest percentage of expressional type, CCDee type (52.47%-59.66%). At the same
      time, in the gene frequency of the four minority nationality populations, the CDe
      frequency was the highest: Miao nationality 0.7244, Buyi nationality 0.7389, Dong
      nationality 0.7410 and Shui nationality 0.7743. CONCLUSION: The Rh blood type
      distribution characteristic of the four minority nationality population, Miao,
      Dong, Buyi and Shui in Guizhou, is similar to that of the minority population in
      Southern China. The Rh negative rate of Miao, Dong and Shui nationality
      populations is lower than that of the Han nationality population(0.33%), only the
      Rh negative rate of Buiyi nationality population is closer or even higher than
      that of the Han nationality population. So that,the hemolysis illness frequency
      in the Rh newborn baby of Guizhou minority nationality population is not high.

PMID- 17029214
TI  - [Polymorphism of five short tandem repeat loci on chromosome X in Hebei Han
      population].
AB  - OBJECTIVE: To investigate the polymorphism of DXS6801, DXS6809, DXS7423, DXS7424,
      DXS9902 five loci in Hebei Han population. METHODS: The PCR products were
      detected by the polyacrylamide gel electrophresis and DNA sequencing analysis.
      RESULTS: Among 114 irrelative males and 118 irrelative females from Hebei Han
      population, 31 alleles were found in the 5 loci. One hundred and one haplotypes
      of the male were detected and the haplotype diversity reached 0.9975. CONCLUSION:
      The five loci are relatively abundant in polymorphic information for
      identification and paternity test. And the obtained data of Hebei Han population
      can be applied to the X-short tandem repeat genetic data bank.

PMID- 17029215
TI  - [hPARP1 genetic polymorphism in southern Chinese Han and Miao populations].
AB  - OBJECTIVE: To study hPARP1 genetic polymorphism in southern Chinese Han and Miao
      populations. METHODS: Blood samples from 187 and 210 southern healthy Han and
      Miao populations were collected. The mutations of exons 12,13,16 and 17 of hPARP1
      gene were investigated by PCR-single-strand conformation polymorphism(SSCP).
      RESULTS: Fragments of 253 bp,313 bp,175 bp,362 bp within exons 12,13,16 and 17
      respectively of hPARP1 gene were amplified by multiple PCR. An SSCP variant in
      exons 12,13,16 and 17 of PARP1 gene in 187 healthy Han and 210 healthy Miao
      individuals was identified. Seven single-base substitutions compared with the
      sequence of PARP1 gene were identified: a T to C transition in exon 12
      (Phe548Ser), a G to T transition in exon 13 (Ala683Ser), a G to T transition in
      exon 16 (Asp798Tyr), and a A to G transition in exon 17 (His808Arg). CONCLUSION:
      There were polymorphism sites in exons 12,13,16,17 of hPARP1 gene in southern
      Chinese Han and Miao populations; these results may be useful for the
      establishment of PARP1 genotyping, and these newly described PARP1 alleles would
      be advantageous indicators for population studies.

PMID- 17029216
TI  - Novel epigenetically deregulated genes in testicular cancer include homeobox
      genes and SCGB3A1 (HIN-1).
AB  - Testicular germ cell tumours (TGCTs) are classified into two main histological
      subgroups: seminomas and non-seminomas. The latter comprise several subtypes:
      embryonal carcinomas, yolk sac tumours, choriocarcinomas, and teratomas. These
      embryonal and extra-embryonal-like differentiation lineages represent a
      caricature of early normal development, and inactivation of gene expression
      through promoter hypermethylation may therefore be of particular importance in
      germ cell tumourigenesis. The promoter methylation status of ten candidate genes
      CDH13, DLX6, EMX2, HOXA9, HOXB5, MSX1, MSX2, RASSF1A, RUNX3, and SCGB3A1 (alias
      HIN-1)-was assessed by methylation-specific PCR in seven intratubular germ cell
      neoplasias and 55 primary TGCTs. Furthermore, by a discovery-based global
      approach, comparing cDNA microarray expression profiles of two germ cell tumour
      cell lines before and after treatment with the demethylating agent 5-aza-2'
      deoxycytidine, a gene list of potentially epigenetic targets was identified, from
      which CGGBP1, CGRRF1, SMARCC2, SORBS1, and XPA were analysed further. Overall,
      the non-seminomas were significantly more often methylated than were seminomas (p
      < 0.001). The three most frequently methylated genes among this subtype were
      SCGB3A1 (54%), RASSF1A (29%), and HOXA9 (26%). CDH13 and HOXB5 were methylated at
      low frequencies (10-15%), and EMX2, MSX1, RUNX3, SORBS1, and XPA only rarely
      (<10%). In conclusion, this study has identified several novel epigenetically
      deregulated target genes in TGCT development, including homeobox genes and
      SCGB3A1, suggesting that epigenetic inactivation of key genes in normal
      development also has an important role in TGCTs.

PMID- 17029217
TI  - Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.
AB  - Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional
      protein. Previous studies have suggested that galectin-3 may play an important
      role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is
      increasingly recognized as a liver condition that may progress to end-stage liver
      disease and based on the known functions of galectin-3, it was hypothesized that
      galectin-3 might play a role in the development of NAFLD. Thus, this study
      investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout
      (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male
      mice at 6 months of age histologically displayed mild to severe fatty change. The
      liver weight per body weight ratio, serum alanine aminotransferase levels, liver
      triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were
      significantly increased compared with those in gal3(+/+) mice. Furthermore, the
      hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE
      (RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were
      increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study
      suggests that the absence of gal3 can cause clinico-pathological features in male
      mice similar to those of NAFLD.

PMID- 17029218
TI  - The presence of an intronic deletion in p73 and high levels of ZEB1 alter the
      TAp73/DeltaTAp73 ratio in colorectal carcinomas.
AB  - TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms
      act as oncogenes through the inactivation of p53 and TAp73. The present study
      analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a
      73 bp deletion in a regulatory region of p73. The clinical relevance of this
      deletion was also examined. ZEB1 can bind to the region repressing p73
      transcription in vitro. The relationship between ZEB1 and p73 variant expression
      levels was studied in the context of this deletion and the levels of the ZEB1
      cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer
      patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73
      (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative
      real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour
      characteristics were examined in each patient. Suppressor and oncogenic isoforms
      of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was
      associated with adverse tumour features. The 73 bp deletion was present in 40% of
      the patients and was associated with adverse pathological parameters of the
      tumours and also with TAp73 down-regulation. In those cases harbouring the
      deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and
      DeltaNp73 correlated directly. Variations in the concentration of p300 affected
      the observed correlations between ZEB1 and the different p73 variants. In
      conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the
      p73 gene and different expression levels of ZEB1 and p300 may act in concert to
      affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In
      addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based
      on its relationship with advanced tumour stage.

PMID- 17029219
TI  - SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular
      carcinoma.
AB  - Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are
      multifunctional matricellular glycoproteins. Recent experimental studies
      suggested that Hevin and SPARC together diminish angiogenesis, but their
      significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed
      to correlate SPARC and Hevin expression with angiogenesis and clinicopathological
      features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens
      were assessed by immunostaining, immunoblotting, and quantitative reverse
      transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was
      assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further
      assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA
      levels were significantly higher in tumours than in non-tumourous livers. A
      significant correlation between tumour SPARC and Hevin mRNA levels was found.
      Moreover, SPARC protein localized in the tumour sinusoidal area correlated
      significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC
      and Hevin proteins were detected in clinical samples. Truncated SPARC protein
      localized in the tumour sinusoidal area correlated significantly with tumour MVD.
      On the other hand, overexpression of full-length SPARC in tumour xenografts in
      athymic nude mice significantly delayed tumour growth, and this delay was related
      to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC
      cells was related to the presence of tumour encapsulation and the absence of
      hepatitis B surface antigen in clinical samples. Overexpression of Hevin in
      tumour xenografts also significantly delayed tumour growth. In conclusion, this
      study has shown that SPARC and Hevin are upregulated in HCC compared with non
      tumourous liver, and that they are inter-related at both mRNA and protein levels.
      Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour
      progression.

PMID- 17029220
TI  - Differential expression and pathological significance of autocrine motility
      factor/glucose-6-phosphate isomerase expression in human lung carcinomas.
AB  - To clarify the involvement of autocrine motility factor (AMF) in the phenotype
      and biological profiles of human lung carcinomas, we analysed protein and mRNA
      expression in a total of 180 cases. Immunohistochemistry revealed positive
      staining in 67.2%, with the highest frequency in squamous cell carcinoma (SCC;
      90.8%) and the lowest in small cell carcinoma (SmCC; 27.8%). In SCC, the staining
      frequency and intensity correlated with the degree of morphological
      differentiation. Generally, the expression levels in immunoblotting analysis
      corresponded well with immunohistochemical positivity. However, there was less
      agreement between protein and mRNA levels: in SmCC and large cell carcinomas
      (LCCs), mRNA showed higher, but protein showed lower expression. Among non-small
      cell lung carcinomas (NSCLCs), AMF protein levels correlated inversely with
      tumour size, but tumours exhibiting lymph node metastasis showed higher mRNA
      expression. In cultured lung carcinoma cells which comprised all histological
      subtypes, AMF was detected in the lysates of all ten cell lines. Secreted AMF
      protein was detected in the conditioned media from six cell lines, most of which
      were SmCC or LCC. Thus, a particular subset of lung carcinomas secrete AMF, which
      may promote cell motility via autocrine stimulation through its cognate receptor
      and cause the biological aggressiveness seen in SmCC and LCC. Moreover, treatment
      by proteasome inhibitors resulted in increased cellular AMF in five cell lines,
      suggesting that intracellular AMF levels are regulated by both secretion and
      proteasome-dependent degradation. In conclusion, AMF was detected in a major
      proportion of lung carcinomas, and may play a part not only in proliferation
      and/or progression of the tumours, but also, possibly, in the differentiation of
      SCC. Furthermore, higher mRNA expression may be related to the high metastatic
      potential of NSCLC and increased protein secretion, leading to a more aggressive
      phenotype, such as the invasiveness of SmCC and LCC.

PMID- 17029221
TI  - Methyltestosterone efficiently induces male development in the self-fertilizing
      hermaphrodite fish, Kryptolebias marmoratus.
AB  - A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that
      reproduces by self-fertilization. In nature, males have been rarely observed. Low
      temperature treatment during late embryonic stages is known to induce males but
      its efficacy is variable. Here we report that 17alpha-methyltestosterone (MT)
      treatment of the embryos converted most of the fish to males. We examined a time
      course of this male induction with histological and marker gene expression
      analyses. Oogenesis started in the gonads of the control embryo at hatching;
      spermatogenesis did not start until two months after hatching. In the MT-treated
      fish, oogenesis started initially as in the control but stopped completely within
      one month after hatching. Instead, spermatogonial proliferation started earlier
      than in the control fish and progressed to full spermatogenesis. Expression
      profiles of the sex-specific marker genes corresponded well with histological
      observations. From one month after hatching, expression of an oocyte-specific
      marker, figalpha, and a testicular somatic cell marker, dmrt1, started to
      increase in the control and in the MT-treated fish, respectively.

PMID- 17029223
TI  - Real-time rigid body motion correction and shimming using cloverleaf navigators.
AB  - Subject motion during scanning can greatly reduce MRI image quality and is a
      major reason for discarding data in both clinical and research scanning. The
      quality of the high-resolution structural data used for morphometric analysis is
      especially compromised by subject movement because high-resolution scans are of
      longer duration. A method is presented that measures and corrects rigid body
      motion and associated first-order shim changes in real time, using a pulse
      sequence with embedded cloverleaf navigators and a feedback control mechanism.
      The procedure requires a 12-s preliminary mapping scan. A single-path, 4.2-ms
      cloverleaf navigator is inserted every repetition time (TR) after the readout of
      a 3D fast low-angle shot (FLASH) sequence, requiring no additional RF pulses and
      minimally impacting scan duration. Every TR, a rigid body motion estimate is made
      and a correction is fed back to adjust the gradients and shim offsets. Images are
      corrected and reconstructed on the scanner computer for immediate access.
      Correction for between-scan motion can be accomplished by using the same
      reference map for each scan repetition. Human and phantom tests demonstrated a
      consistent improvement in image quality if motion occurred during the
      acquisition.

PMID- 17029224
TI  - Dynamic coil selection for real-time imaging in interventional MRI.
AB  - MR-guided intravascular interventions require image update rates of up to 10
      images per second, which can be achieved using parallel imaging. However,
      parallel imaging requires many coil elements, which increases reconstruction
      times and thus compromises real-time image reconstruction. In this study a
      dynamic coil selection (DCS) algorithm is presented that selects a subset of
      receive coils to reduce image reconstruction times. The center-of-sensitivity
      coordinates and the relative signal intensities are determined for each coil in a
      prescan. During the intervention m coils are selected for reconstruction using a
      coil ranking based on the distance to the current slice or catheter position. In
      a phantom experiment for m = 6, an optimal signal-to-background ratio (SBR) was
      achieved and foldover artifacts were avoided. In three animal experiments
      involving catheter manipulation in the aorta and the right heart chamber, the
      anatomy was successfully visualized at frame rates of about 5 Hz using active
      catheter tracking.

PMID- 17029225
TI  - T2 measurement and quantification of glutamate in human brain in vivo.
AB  - The proton NMR transverse relaxation time T(2) of glutamate (Glu) in human brain
      was measured by means of spectrally selective refocusing at 3.0 T in vivo. An
      81.4-ms-long dual-band Gaussian 180 degrees RF pulse, designed for refocusing at
      2.35 and 3.03 ppm, was employed within point-resolved spectroscopy (PRESS) to
      generate the Glu C4-proton target multiplet and the total creatine (tCr) singlet.
      Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical
      analysis of the filtering performance for effective detection of the Glu signal
      with minimal contamination from glutamine (Gln), N-acetylaspartate (NAA), and
      glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral
      fitting of experimental and calculated spectra. Apparent T(2) values of Glu and
      tCr were estimated as 201 +/- 18 and 164 +/- 12 ms for the medial prefrontal (PF)
      cortex, and 198 +/- 22 and 169 +/- 15 ms (mean +/- SD, N = 5) for the left
      frontal (LF) cortex, respectively. With water segmentation data, the
      magnetization values of Glu and tCr of the two adjacent voxels, calculated from
      the T(2) values and spectra following the thermal equilibrium magnetization, were
      combined to give the Glu and tCr concentrations as 10.37 +/- 1.06 and 8.87 +/-
      0.56 mM for gray matter (GM), and 5.06 +/- 0.57 and 5.16 +/- 0.45 mM (mean +/-
      SD, N = 5) for white matter (WM), respectively.

PMID- 17029227
TI  - An algorithm for the automated quantitation of metabolites in in vitro NMR
      signals.
AB  - The quantitation of metabolite concentrations from in vitro NMR spectra is
      hampered by the sensitivity of peak positions to experimental conditions. The
      quantitation methods currently available are generally labor intensive and cannot
      readily be automated. Here, an algorithm is presented for the automatic time
      domain analysis of high-resolution NMR spectra. The TARQUIN algorithm uses a set
      of basis functions obtained by quantum mechanical simulation using predetermined
      parameters. Each basis function is optimized by subdividing it into a set of
      signals from magnetically equivalent spins and varying the simulated chemical
      shifts of each of these groups to match the signal undergoing analysis. A novel
      approach to the standard multidimensional minimization problem is introduced
      based on evaluating the fit resulting from different permutations of possible
      chemical shifts, obtained from one-dimensional searches. Results are presented
      from the analysis of (1)H proton magic angle spinning spectra of cell lines
      illustrating the robustness of the method in a typical application. Simulation
      was used to investigate the biggest peak shifts that can be tolerated.

PMID- 17029226
TI  - T2* measurement during first-pass contrast-enhanced cardiac perfusion imaging.
AB  - First-pass contrast-enhanced (CE) myocardial perfusion imaging will experience
      T(2) (*) effects at peak concentrations of contrast agent. A reduction in the
      signal intensity of left ventricular (LV) blood due to T(2) (*) losses may effect
      estimates of the arterial input function (AIF) used for quantitative perfusion
      measurement. Imaging artifacts may also result from T(2) (*) losses as well as
      off-resonance due to the bolus susceptibility. We hypothesized that T(2) (*)
      losses would not be significant for measurement of the AIF in full-dose studies
      using a short echo time (TE = 0.6 ms). The purpose of this study was to directly
      measure T(2) (*) in the LV cavity during first-pass perfusion. For single-dose Gd
      DTPA (0.1 mmol/kg at 5 ml/s), the LV blood pool T(2) (*) had a mean value of 9 ms
      (N = 10) at peak enhancement. Distortion of the AIF due to T(2) (*) signal
      intensity loss will be less than 10% using TE = 0.6 ms.

PMID- 17029228
TI  - Three-dimensional prepolarized magnetic resonance imaging using rapid acquisition
      with relaxation enhancement.
AB  - Prepolarized MRI (PMRI) with pulsed electromagnets has the potential to produce
      diagnostic quality 0.5- to 1.0-T images with significantly reduced cost,
      susceptibility artifacts, specific absorption rate, and gradient noise. In PMRI,
      the main magnetic field cycles between a high field (B(p)) to polarize the sample
      and a homogeneous, low field (B(0)) for data acquisition. This architecture
      combines the higher SNR of the polarizing field with the imaging benefits of the
      lower field. However, PMRI can only achieve high SNR efficiency for volumetric
      imaging with 3D rapid imaging techniques, such as rapid acquisition with
      relaxation enhancement (RARE) (FSE, TSE), because slice-interleaved acquisition
      and longitudinal magnetization storage are both inefficient in PMRI. This paper
      demonstrates the use of three techniques necessary to achieve efficient, artifact
      free RARE in PMRI: quadratic nulling of concomitant gradient fields,
      electromotive force cancelation during field ramping, and phase compensation of
      CPMG echo trains. This paper also demonstrates the use of 3D RARE in PMRI to
      achieve standard T(1) and fat-suppressed T(2) contrast in phantoms and in vivo
      wrists. These images show strong potential for future clinical application of
      PMRI to extremity musculoskeletal imaging and peripheral angiography.

PMID- 17029229
TI  - In vivo MRI of cancer cell fate at the single-cell level in a mouse model of
      breast cancer metastasis to the brain.
AB  - Metastasis (the spread of cancer from a primary tumor to secondary organs) is
      responsible for most cancer deaths. The ability to follow the fate of a
      population of tumor cells over time in an experimental animal would provide a
      powerful new way to monitor the metastatic process. Here we describe a magnetic
      resonance imaging (MRI) technique that permits the tracking of breast cancer
      cells in a mouse model of brain metastasis at the single-cell level. Cancer cells
      that were injected into the left ventricle of the mouse heart and then delivered
      to the brain were detectable on MR images. This allowed the visualization of the
      initial delivery and distribution of cells, as well as the growth of tumors from
      a subset of these cells within the whole intact brain volume. The ability to
      follow the metastatic process from the single-cell stage through metastatic
      growth, and to quantify and monitor the presence of solitary undivided cells will
      facilitate progress in understanding the mechanisms of brain metastasis and tumor
      dormancy, and the development of therapeutics to treat this disease.

PMID- 17029230
TI  - Proton MRI as a noninvasive tool to assess elastase-induced lung damage in
      spontaneously breathing rats.
AB  - Elastase-induced changes in lung morphology and function were detected in
      spontaneously breathing rats using conventional proton MRI at 4.7 T. A single
      dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline)
      was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid
      signals were detected in the lungs 24 hr after administration of elastase and
      resolved within 2 weeks. These results correlated with perivascular edema and
      cellular infiltration observed histologically. Reductions in MRI signal intensity
      of the lung parenchyma, and increases in lung volume were detected as early as 2
      weeks following elastase administration and remained uniform throughout the
      study, which lasted 8 weeks. Observations were consistent with air trapping
      resulting from emphysema detected histologically. In a separate experiment,
      animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid
      (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on
      day 21 after elastase administration and continuing for 12 days. Under these
      conditions, ATRA did not elicit a reversal of elastase-induced lung damage as
      measured by MRI and histology. The present approach complements other validated
      applications of proton MRI in experimental lung research as a method for
      assessing drugs in rat models of respiratory diseases.

PMID- 17029231
TI  - Microvessel density estimation in the human brain by means of dynamic contrast
      enhanced echo-planar imaging.
AB  - Animal studies have shown that in vivo estimates of microvessel density in the
      brain may be obtained from an MRI-measurable index (Q) provided that a
      sufficiently high dose of an intravascular paramagnetic contrast agent is
      employed. Q is determined from the shifts in the transverse relaxation rates
      induced by the contrast agent, and a high dose is required for the validity of
      analytic expressions relating Q to the microvessel density. However, the steady
      state imaging techniques used in these prior investigations are not appropriate
      for humans, as the required contrast agent dose is too large. Here results of a
      pilot study with three subjects are reported. The results suggest that reliable Q
      measurements can be performed in the human brain at 1.5 T by using an interleaved
      spin-echo (SE)/gradient-echo (GE) echo-planar imaging (EPI) sequence and a bolus
      injection of a triple dose of Gd-DTPA. Lower- and upper-bound estimates for the
      microvessel density were derived from the Q-values, and were found to be in
      reasonable accord with previously cited values determined by histology.

PMID- 17029232
TI  - Behavior of ordered sodium in enzymatically depleted cartilage tissue.
AB  - The onset of cartilage tissue disorders can be characterized by a loss of
      proteoglycans (PGs) and diagnosed by contrast-enhanced proton ((1)H) MRI
      techniques, as well as sodium MRI. The behavior of sodium located in anisotropic
      environments, is examined as a function of cartilage degeneration. PGs are
      proteolytically depleted from the cartilage samples, which gives rise to a
      decrease of the ordered sodium content. More surprisingly, however, the residual
      quadrupolar couplings are shown to increase with increasing depletion levels.
      Since the residual quadrupolar couplings are intimately related to local order
      and anisotropic motion, measuring their distribution in cartilage may provide
      insight into the structural changes that occur within the tissue upon
      degradation. In this study relatively mild orientational dependence of the
      couplings was found. Little or no free sodium was observed in the cartilage
      specimens under study.

PMID- 17029233
TI  - Magnetic resonance angiography reveals therapeutic enlargement of collateral
      vessels induced by VEGF in a murine model of peripheral arterial disease.
AB  - PURPOSE: To quantify spontaneous and therapeutic arteriogenesis in vivo in a
      murine model of peripheral arterial disease using magnetic resonance angiography.
      MATERIALS AND METHODS: Male, 8-12-week-old, C57/BL6 mice underwent femoral artery
      ligation; 21 days later, 2 mg/kg recombinant murine VEGF165, formulated for slow
      release, was injected into the ipsilateral gastrocnemius. The spontaneous
      (following ligation) and therapeutic (following vascular endothelial growth
      factor (VEGF)) formation of collateral vessels was quantified using 3D magnetic
      resonance angiography on a small-bore 4.7T system. Therapeutically induced
      angiogenesis and blood flow were quantified using an in situ anti-platelet
      endothelial cell adhesion molecule (PECAM) 1 radioimmunoassay and radiolabeled
      microsphere deposition, respectively. RESULTS: Spontaneous arteriogenesis was
      visible in all animals five days after ligation. VEGF treatment doubled the
      arteriogenic response five days after treatment compared to vehicle (cross
      sectional area of vessels: 0.96 vs. 0.46 mm2, P<0.01). VEGF also induced
      angiogenesis (PECAM1 levels 191% of vehicle, P<0.05) and increased blood flow
      specific to the injection site (57 vs. 7 mL/minute/100 g, P<0.05). CONCLUSION:
      The presented methodology allowed in vivo quantification of spontaneous
      arteriogenesis in a murine model of peripheral arterial disease and demonstrated
      that therapeutic enlargement of collateral vessels is possible with VEGF.

PMID- 17029234
TI  - Novel approach for alpha-helical topology prediction in globular proteins:
      generation of interhelical restraints.
AB  - The protein folding problem represents one of the most challenging problems in
      computational biology. Distance constraints and topology predictions can be
      highly useful for the folding problem in reducing the conformational space that
      must be searched by deterministic algorithms to find a protein structure of
      minimum conformational energy. We present a novel optimization framework for
      predicting topological contacts and generating interhelical distance restraints
      between hydrophobic residues in alpha-helical globular proteins. It should be
      emphasized that since the model does not make assumptions about the form of the
      helices, it is applicable to all alpha-helical proteins, including helices with
      kinks and irregular helices. This model aims at enhancing the ASTRO-FOLD protein
      folding approach of Klepeis and Floudas (Journal of Computational Chemistry
      2003;24:191-208), which finds the structure of global minimum conformational
      energy via a constrained nonlinear optimization problem. The proposed topology
      prediction model was evaluated on 26 alpha-helical proteins ranging from 2 to 8
      helices and 35 to 159 residues, and the best identified average interhelical
      distances corresponding to the predicted contacts fell below 11 A in all 26 of
      these systems. Given the positive results of applying the model to several
      protein systems, the importance of interhelical hydrophobic-to-hydrophobic
      contacts in determining the folding of alpha-helical globular proteins is
      highlighted.

PMID- 17029235
TI  - Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana.
AB  - AtFKBP13, an immunophilin in the chloroplast thylakoid lumen, participates in
      redox-regulatory processes via a pair of conserved disulfide bonds that are
      present at the N- and C-termini of the protein. Characterization of this protein
      by structural and biochemical analysis has revealed a novel mechanism of redox
      regulation in the thylakoid lumen. The protein is active in its oxidized form but
      is inactivated after reduction by the thioredoxin system. This is in sharp
      contrast with the regulation of biosynthetic enzymes in the stroma of the
      chloroplast, where reduction of enzymes by thioredoxin activates their function.
      To understand how the reduced form of AtFKBP13 is stabilized and how reduction of
      the cysteine residues affects the molecular properties of the enzyme, we
      determined the crystal structure of reduced AtFKBP13 at 1.88 A. Comparison of the
      reduced structure and the oxidized form that we published earlier shows
      rearrangements in redox site regions, readjustments of hydrogen-bonding
      interactions and the secondary structure of the active site residues 50-53, and
      reduced accessibility of the catalytic residues involved in the peptidyl proline
      isomerase (PPIase) activity of this enzyme. We propose that redox-linked changes
      in the secondary structure of the PPIase domain are responsible for significant
      functional differences in this protein in the reduced and oxidized states.

PMID- 17029236
TI  - Chemodosimetry of in vivo tumor liposomal drug concentration using MRI.
AB  - Effective cancer chemotherapy depends on the delivery of therapeutic drugs to
      cancer cells at cytotoxic concentrations. However, physiologic barriers, such as
      variable vessel permeability, high interstitial fluid pressure, and heterogeneous
      perfusion, make it difficult to achieve that goal. Efforts to improve drug
      delivery have been limited by the lack of noninvasive tools to evaluate
      intratumoral drug concentration and distribution. Here we demonstrate that tumor
      drug concentration can be measured in vivo using T(1)-weighted MRI, following
      systemic administration of liposomes containing both drug (doxorubicin (DOX)) and
      contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using
      T(1) relaxation times and Mn:DOX loading ratios, as previously described. Two
      independent validations by high-performance liquid chromatography (HPLC) and
      histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant
      linear relationship between DOX concentrations determined using T(1) and those
      measured invasively. This method of imaging exhibits potential for real-time
      evaluation of chemotherapeutic protocols and prediction of tumor response on an
      individual patient basis.

PMID- 17029237
TI  - Phototoxicity and fluorotoxicity combine to alter the behavior of neutrophils in
      fluorescence microscopy based flow adhesion assays.
AB  - The use of fluorescent probes that allow visualization of leukocyte-endothelial
      cell (EC) interactions has greatly informed our understanding of leukocyte
      recruitment. However, effects of these agents on the biological functions of
      leukocytes are poorly described, leading to concerns about the interpretation of
      such data. Here we used two flow-based neutrophil adhesion assays to compare the
      effects of phase contrast illumination (PCI) with high intensity illumination
      (HII) used for fluorescent microscopy, in the presence or absence of five
      commonly used fluorochromes. Isolated neutrophils were either (1) perfused across
      P-selectin to establish a population of rolling cells, which were subsequently
      activated with fMLP; or (2) perfused across EC activated with TNF-alpha. In the
      absence of fluorescent dyes, HII did not affect levels of leukocyte adhesion;
      however, subsequent neutrophil behavior was dramatically altered when compared
      with cells under PCI, for example, dramatically reducing their migration
      velocities. In the presence of fluorescent dyes, the effects of HII were
      exacerbated, although the precise nature of the biological effects of these
      probes was agent specific. Thus, for the first time, our experiments describe the
      effects of fluorescent microscopy on the separate stages of the neutrophil
      recruitment process and reveal a previously unsuspected effect of HII on
      neutrophil migration.

PMID- 17029238
TI  - Thermovoltaic properties of hornet silk.
AB  - In silk from the larval silk caps of the Oriental hornet Vespa orientalis
      (Hymenoptera, Vespinae), temperature-dependent changes in the electric voltage
      have been recorded, with rise in the voltage occurring mainly upon rise in the
      temperature between 10-36 degrees C. The peak voltage was measured between 32-38
      degrees C and attained 240-360 mV, but with further increase in temperature, the
      voltage decreased, dropping to 0 mV at about 45-50 degrees C. Upon second
      measurement (of same silk specimen), the voltage peak usually occurred later (by
      8-9 degrees C) and at higher temperature than in the first measurement.
      Continuous measurements during warming up to 30 degrees C followed by cooling
      down to 15 degrees C yielded an hysteresis between the warming "line" and the
      cooling "line", the former often straight and the latter usually curved.
      Maintaining the silk specimen at a fixed temperature for a prolonged period
      (hours) initially causes the voltage to rise, then remain steady, and finally
      drop. Boiling the silk caps in tap water for 7-10 min exerts some changes in the
      silk properties, mainly a decrease in voltage level. The general behavior of the
      silk suggests that it is a polymer endowed with the qualities of an organic
      semiconductor. The various properties of the larval silk are discussed in great
      detail.

PMID- 17029239
TI  - Analysis of changes in optical fibers during arc-fusion splicing by use of
      quantitative phase imaging.
AB  - A non-interferometric imaging technique in conjunction with Abel inversion is
      used to directly and quantitatively examine the changes in optical fibers due to
      the heating produced during arc-fusion splicing as a function of fusion arc
      parameters. Phase images in the vicinity of a fusion splice are obtained using
      Quantitative Phase Microscopy, allowing the refractive-index change to be
      reconstructed with high spatial resolution. This simple, nondestructive method
      confirms that, for a fixed arc current, while the fusion time increases, the
      refractive-index of both fiber cores within the fusion region decreases in
      magnitude, the core region broadens, and the axial gradient decreases.

PMID- 17029240
TI  - Anatomy of the frontal gland and ultramorphology of the frontal tube in the
      soldier caste of species of Nasutitermitinae (Isoptera, Termitidae).
AB  - All termite species (Isoptera) are eusocial. These insects live in societies
      where the division of labor is a predominant characteristic, conditioned by the
      presence of castes with different morphology, ontogeny, and development. The
      soldier caste is unique among social insects and it is responsible for colony
      defense. Soldiers belonging to the Nasutitermitinae subfamily are very peculiar,
      since they may be polymorphic and present a nasus in addition to either developed
      or vestigial mandibles. The defensive secretions of soldiers of the neotropical
      Nasutitermitinae have been the aim of several chemical studies, but few data
      exist concerning the anatomy and histology of the exocrine glands. This article
      presents a comparative study on the anatomy of the frontal gland of soldiers of
      several Nasutitermitinae species: Syntermes dirus (Burmeister), Syntermes nanus
      (Constantino), Constrictotermes cyphergaster (Silvestri), Nasutitermes corniger
      (Motschulsky) and Velocitermes heteropterus (Silvestri), with emphasis on the
      ultramorphology and ultrastructure of the frontal tube.

PMID- 17029241
TI  - Identification of a new subfamily of HNH nucleases and experimental
      characterization of a representative member, HphI restriction endonuclease.
AB  - The restriction endonuclease (REase) R. HphI is a Type IIS enzyme that recognizes
      the asymmetric target DNA sequence 5'-GGTGA-3' and in the presence of Mg(2+)
      hydrolyzes phosphodiester bonds in both strands of the DNA at a distance of 8
      nucleotides towards the 3' side of the target, producing a 1 nucleotide 3'
      staggered cut in an unspecified sequence at this position. REases are typically
      ORFans that exhibit little similarity to each other and to any proteins in the
      database. However, bioinformatics analyses revealed that R.HphI is a member of a
      relatively big sequence family with a conserved C-terminal domain and a variable
      N-terminal domain. We predict that the C-terminal domains of proteins from this
      family correspond to the nuclease domain of the HNH superfamily rather than to
      the most common PD-(D/E)XK superfamily of nucleases. We constructed a three
      dimensional model of the R.HphI catalytic domain and validated our predictions by
      site-directed mutagenesis and studies of DNA-binding and catalytic activities of
      the mutant proteins. We also analyzed the genomic neighborhood of R.HphI homologs
      and found that putative nucleases accompanied by a DNA methyltransferase (i.e.
      predicted REases) do not form a single group on a phylogenetic tree, but are
      dispersed among free-standing putative nucleases. This suggests that nucleases
      from the HNH superfamily were independently recruited to become REases in the
      context of RM systems multiple times in the evolution and that members of the HNH
      superfamily may be much more frequent among the so far unassigned REase sequences
      than previously thought.

PMID- 17029242
TI  - Crystal structure of XC5357 from Xanthomonas campestris: a putative
      tetracenomycin polyketide synthesis protein adopting a novel cupin subfamily
      structure.

PMID- 17029243
TI  - The crystal structure of XC847 from Xanthomonas campestris: a 3'-5'
      oligoribonuclease of DnaQ fold family with a novel opposingly shifted helix.

PMID- 17029245
TI  - Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients:
      non-infectious and long-term complications.
AB  - Pulmonary complications are among the most frequently encountered sequelae of
      pediatric hematopoietic stem cell transplantation (HSCT). Non-infectious
      complications are becoming increasingly more common in this unique population.
      This review addresses the diagnosis and management of non-infectious
      manifestations of lung disease in pediatric HSCT patients and briefly discusses
      the long-term pulmonary function of childhood HSCT survivors.

PMID- 17029244
TI  - Modulation of connexin expression and gap junction communication in astrocytes by
      the gram-positive bacterium S. aureus.
AB  - Gap junctions establish direct intercellular conduits between adjacent cells and
      are formed by the hexameric organization of protein subunits called connexins
      (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS
      infection with S. aureus, one of the main etiologic agents of brain abscess in
      humans, is capable of eliciting regional changes in astrocyte homocellular gap
      junction communication (GJC) and, by extension, influencing neuron homeostasis at
      sites distant from the primary focus of infection. Here we investigated the
      effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30,
      and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial
      stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however,
      Cx26 levels were elevated following bacterial exposure. Functional examination of
      dye coupling, as revealed by single-cell microinjections of Lucifer yellow,
      demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of
      protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly
      modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be
      regulated by a factor(s) that requires de novo protein production; however, CHX
      did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK
      inhibitor SB202190 was capable of partially restoring the S. aureus-mediated
      decrease in astrocyte GJC to that of unstimulated cells, suggesting the
      involvement of p38 MAPK-dependent pathway(s). These findings could have important
      implications for limiting the long-term detrimental effects of abscess formation
      in the brain which may include seizures and cognitive deficits.

PMID- 17029247
TI  - Validity and consequence of informed consent in pediatric bone marrow
      transplantation: The parental experience.
AB  - BACKGROUND: Conditions supporting a high quality of consent for pediatric bone
      marrow transplantation (BMT) are suboptimal given the complexity of the
      procedure, lack of options, and parent emotional duress. We studied if parents
      perceived choice when consenting to BMT, if they felt the consent provided was
      valid, and how the consent process affected them. METHODS: Telephone or face-to
      face interviews were recorded using a semi-structured interview outline.
      Interview transcripts were anonymized, and independently analyzed by three
      reviewers. RESULTS: Twenty parents of twelve children participated, including
      five bereaved parents. There were no differences in patient transplant
      characteristics between the eligible and study groups. Divorced or separated
      parents were underrepresented in the participant group. Fifteen parents felt
      personally compelled to consent; most (18) denied feeling external medical
      pressure to do so. All parents felt their consent was valid and most reported
      adequate levels of freedom, capacity, and information. Expectations formulated
      during the consent process strongly influenced parents' experience post-BMT. Good
      communication during consent contributed to trust and therapeutic alliance with
      physicians following BMT. Late parental stress and anxiety were periodic, but
      very high in some families. CONCLUSIONS: Parents feel consent for pediatric BMT
      is valid, despite feeling personally compelled to consent. Strategies aimed at
      nurturing hope and realistic expectations may assist in improving the consent
      process, while diminishing long-term stressors.

PMID- 17029246
TI  - Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients:
      overview, diagnostic considerations, and infectious complications.
AB  - Pulmonary complications are among the most common and serious sequelae seen in
      hematopoietic stem cell transplantation (HSCT) recipients. This two-part review
      addresses the incidence and impact of pulmonary complications in pediatric HSCT
      patients. In this first part we review the available data for the use of
      diagnostic modalities in this population, including flexible bronchoscopy with
      bronchoalveolar lavage (BAL) and open lung biopsy (OLB). We also review the many
      infectious pulmonary complications that may occur in pediatric HSCT recipients,
      utilizing the traditional chronologic divisions of neutropenic phase (0-30 days
      following HSCT), early phase (30-100 days), and late phase (>100 days).

PMID- 17029248
TI  - Risk factors for extraocular relapse following enucleation after failure of
      chemoreduction in retinoblastoma.
AB  - OBJECTIVE: To assess the outcome and determine risk factors for extraocular
      relapse in patients with retinoblastoma who had been enucleated after failure of
      chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions.
      Pathological risk factors (PRF) were defined as invasion of the anterior segment,
      choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the
      local pathology report. Extraocular relapse was defined as an event. RESULTS: One
      hundred twenty-two patients were included (17 had bilateral enucleation).
      Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%),
      vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty
      five also received external beam radiotherapy (28.7%). PRF included: 39 with
      choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post
      laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given
      to eight patients (6.5%) because of scleral invasion. Four patients had an
      extraocular relapse after enucleation, two of whom survive after intensive
      treatment including stem cell rescue. Five-year probability of event-free
      survival is 0.96. Only scleral invasion and bilateral enucleation were
      significantly associated with extraocular relapse. CONCLUSIONS: The risk of
      extraocular relapse is low after enucleation following failure of chemoreduction.
      Patients who underwent bilateral enucleation and those with scleral invasion are
      at higher risk of extraocular relapse.

PMID- 17029249
TI  - The role of angiotensin II in stress urinary incontinence: A rat model.
AB  - AIMS: Pharmacological treatment for stress urinary incontinence (SUI) is limited
      to the use of non-selective alpha-agonists, which are often ineffective. Non
      adrenergic mechanisms have also been implicated in urethral closure, including
      angiotensin II (Ang-II), which has been demonstrated throughout the urinary
      tract. We investigate the role of Ang-II in urethral tone in a rat model of SUI.
      METHODS: Abdominal leak point pressure (ALPP) and retrograde urethral pressure
      profilometry (RLPP) were measured in 70 female virgin rats. Thirty rats underwent
      pudendal nerve injury (PNT), 30 had circumferential urethrolysis (U-Lys), and 10
      had sham surgery. Rats received daily doses of Angiotensin Type 1 (AT-1) receptor
      inhibitor (20 mg/kg), Angiotensin Type 2 (AT-2) receptor antagonist (10 mg/kg),
      or Ang-II (2 mg/kg). RESULTS: Following U-Lys, RLPP and ALPP decreased from 21.4
      +/- 2.0 and 39.2 +/- 3.3 mm Hg, to 13.1 +/- 1.5 and 21.6 +/- 1.9 mmHg,
      respectively (P < 0.01). After PNT, RLPP, and ALPP decreased from 21.0 +/- 1.6
      and 41.9 +/- 3.0 mmHg to 13.1 +/- 1.5 and 24.7 +/- 3.3 mmHg, respectively (P <
      0.01). AT-1 inhibitor caused significant decrease in RLPP and ALPP from 21.0 +/-
      6.2 and 41.8 +/- 9.4 mmHg, to 12.0 +/- 3.8 and 25.6 +/- 6.6 mmHg, respectively (P
      < 0.01). Likewise, AT-2 treatment reduced RLPP and ALPP from 21.4 +/- 6.3 and
      40.1 +/- 1.7 mmHg, to 13.5 +/- 5.7 and 31.0 +/- 7.2 mmHg, respectively (P <
      0.01). Following surgery, Ang-II administration restored RLPP and ALPP to
      baseline presurgical values. CONCLUSIONS: AT-1 and AT-2 receptor inhibition
      significantly lowers urethral resistance, comparable to either neurogenic or
      urethrolytic injury. Ang-II treatment restored urethral tone in rats with
      intrinsic sphincter dysfunction. Ang II appears to serve a functional role in the
      maintenance of urethral tone and stress continence.

PMID- 17029250
TI  - Influence of temperature on urethra to bladder micturition reflex in the awake
      ewe.
AB  - AIMS: The flow of fluid along the urethra is known to facilitate detrusor
      contraction during micturition. This reflex, previously described in awake ewes,
      helps to achieve complete bladder emptying. In anesthetized cats, another urethra
      to bladder reflex involving urethral cold receptors has been described. The aim
      of this study was to investigate whether the urethral reflex first described in
      awake ewes could also be temperature-dependent. METHODS: Experiments were
      performed on 10 healthy ewes. Urethral flows were performed by injecting 10 ml
      saline (ranging from 17 to 43 degrees C) at the level of the proximal urethra.
      Catheterization of the bladder was performed so that detrusor pressure was
      continually recorded during the experiments. RESULTS: Urethral flows using body
      temperature saline (37-39 degrees C) consistently evoked detrusor contraction.
      Urethral flows using saline at temperatures between 40 and 43 degrees C induced
      detrusor contractions that were not significantly different from those observed
      at 37-39 degrees C. Urethral flows using saline at temperatures below 37-39
      degrees C (17-36 degrees C) resulted in a weaker or absent detrusor contraction.
      CONCLUSIONS: In ewes, we have shown that urethral to bladder micturition reflex
      involving mechanoreceptors is decreased at temperatures below the physiological
      range. It is suggested that transient receptor potential vanilloid cation
      channels (e.g., TRPV4 which is activated by sheer/stress flows at near-body
      temperature) could be involved in this urethra to bladder reflex. In humans, this
      reflex has hardly been described and is still a matter of debate. Our results
      reinforce that its full investigation may require systematic use of a range of
      saline flows at different temperatures.

PMID- 17029252
TI  - Modular neuropile organization in the Drosophila larval brain facilitates
      identification and mapping of central neurons.
AB  - Elucidating how neuronal networks process information requires identification of
      critical individual neurons and their connectivity patterns. For this purpose, we
      used the third-instar Drosophila larval brain and applied reverse-genetic tools,
      immunolabeling procedures, and 3D digital reconstruction software. Consistent
      topological definition of neuropile compartments in the larval brain can be
      obtained through simple fluorescence-immunolabeling methods. The modular
      neuropiles can be used as a fiducial framework for mapping the projection
      patterns of individual neurons labeled with green fluorescent protein (GFP). GFP
      labeled neurons often exhibit dendrite-like arbors as well as clustered varicose
      terminals on neurite branches that innervate identifiable neuropile compartments.
      We identified candidate cholinergic interneurons in genetic mosaic brains that
      overlap with the larval optic nerve terminus. By using the neuropile framework,
      we demonstrate that the candidate visual interneurons are not a subset of the
      previously identified circadian pacemaker neurons that also contact the larval
      optic nerve terminus; they may represent parallel pathways in the processing of
      visual inputs. Thus, in the Drosophila larval brain, modular neuropiles can be
      used as a framework for systematically identifying, mapping, and classifying
      interneurons; understanding their roles in behavior can then be pursued further.

PMID- 17029251
TI  - Galpha encoding gene family of the malaria vector mosquito Anopheles gambiae:
      expression analysis and immunolocalization of AGalphaq and AGalphao in female
      antennae.
AB  - To initiate a comprehensive investigation of chemosensory signal transduction
      downstream of odorant receptors, we identified and characterized the complete set
      of genes that encode G-protein alpha subunits in the genome of the malaria vector
      mosquito An. gambiae. Data are provided on the tissue-specific expression
      patterns of 10 corresponding aga-transcripts in adult mosquitoes and pre-imago
      developmental stages. Specific immunoreactivity in chemosensory hairs of female
      antennae provides evidence in support of the participation of a subset of
      AGalphaq isoforms in olfactory signal transduction in this mosquito. In contrast,
      AGalphao is localized along the flagellar axon bundle but is absent from
      chemosensory sensilla, which suggests that this G-protein alpha subunit does not
      participate in olfactory signal transduction.

PMID- 17029253
TI  - Estradiol-induced modulation of estrogen receptor-beta and GABA within the adult
      neocortex: a potential transsynaptic mechanism for estrogen modulation of BDNF.
AB  - Estrogen influences brain-derived neurotrophic factor (BDNF) expression in the
      neocortex. However, BDNF-producing cortical neurons do not express detectable
      levels of nuclear estrogen receptors; instead, the most abundant cortical nuclear
      estrogen receptor, ER-beta, is present in GABAergic neurons, prompting us to test
      the hypothesis that estrogen effects on BDNF are mediated via cortical inhibitory
      interneurons. Adult female ovariectomized rats were provided acute estrogen
      replacement and the number of cortical GABA, ER-beta, and ER-beta/GABA double
      labeled neurons was examined. Within 48 hours of injection of 17-beta-estradiol,
      the number of perirhinal neurons double-labeled for ER-beta/GABA was reduced by
      28% (P<0.01 compared to vehicle-treated ovariectomized controls), and all cells
      expressing detectable levels of GABA were reduced by 19% (P<0.01). To investigate
      potential relationships between estrogen receptors, GABAergic neurons, and BDNF
      expressing cells, brain sections were double- or triple-labeled for ER-beta,
      GABAergic, and BDNF immunomarkers. The findings indicated that ER-beta-bearing
      inhibitory neurons project onto other GABAergic neurons that lack nuclear
      estrogen receptors; these inhibitory neurons in turn innervate BDNF-expressing
      excitatory cells. High estrogen states reduce cortical GABA levels, presumably
      releasing inhibition on BDNF-expressing neurons. This identifies a putative two
      step transsynaptic mechanism whereby estrogen availability modulates expression
      of inhibitory transmitters, resulting in increased BDNF expression.

PMID- 17029254
TI  - Transitory uptake of serotonin in the developing sensory pathways of the common
      marmoset.
AB  - Serotonin (5-HT) affects brain development during sensitive developmental
      periods. In rodents, transient sites of high affinity capture of 5-HT were
      demonstrated in the primary sensory neurons and in the sensory thalamocortical
      afferents. This uptake is required to adjust 5-HT receptor stimulation during the
      formation of sensory maps. To determine whether similar mechanisms exist in
      primates, we analyzed staged embryos and postnatal pups in the common marmoset
      (total gestation time, 142 days). Immunocytochemical analyses were performed
      using antisera to 5-HT, to the serotonin transporter (SERT), and to the vesicular
      monoamine transporter (VMAT2). 5-HT, SERT, and VMAT2 labeled the raphe neurons
      and their terminal network from embryonic day (E)70 to adulthood. In addition,
      from E70-130 VMAT2 and SERT were observed in all the sensory cranial nerves, the
      olfactory nerve, the gustatory, the trigeminal, the auditory fibers, in the
      retinal ganglion cells, and the optic tract up to the lateral geniculate nucleus
      and the superior colliculus. All the spinal sensory ganglia and their peripheral
      sensory branches were labeled. Accumulation of 5-HT was observed in all the
      sensory neurons expressing SERT and the corresponding axon tracts. Since these
      neurons were missing tryptophan hydroxylase (TPH), the synthesizing enzyme for 5
      HT, they most likely accumulated 5-HT through the action of the amine
      transporters, as has been shown in rodents. No transient expression of 5-HT
      markers was detectable in the sensory thalamocortical axons at any of the ages
      examined. Thus, the existence of 5-HT uptake in nonserotoninergic neurons appears
      to be a conserved feature in primates, although the topographic extent of this
      transient expression is more restricted than that previously demonstrated in
      rodents.

PMID- 17029256
TI  - Bone morphogenetic protein-4 expression in the adult rat brain.
AB  - Bone morphogenetic protein-4 (BMP4) is a member of the transforming growth factor
      beta (TGF-beta) superfamily and plays important roles in multiple biological
      events. Although BMP4 expression has been well described in the early development
      of the central nervous system (CNS), little information is available on its
      expression in the adult CNS. Therefore, we investigated BMP4 expression in the
      adult rat CNS by using immunohistochemistry. BMP4 is intensely expressed in most
      neurons and their dendrites. In addition, intense BMP4 expression was also
      observed in the neuropil of the gray matters where high plasticity is reported,
      such as the molecular layer of the cerebellum and the superficial layer of the
      superior colliculus. Furthermore, we found that astrocytes also express BMP4
      protein. These data indicate that BMP4 is more widely expressed throughout the
      adult CNS than previously reported, and its continued abundant expression in the
      adult brain strongly supports the idea that BMP4 plays pivotal roles also in the
      adult brain.

PMID- 17029257
TI  - Primary and secondary sensory trigeminal projections in a cyprinid teleost, carp
      (Cyprinus carpio).
AB  - Primary and secondary sensory trigeminal projections were studied by means of
      tract-tracing methods in a cyprinid teleost, the carp. Tracer injections into the
      trigeminal nerve root labeled terminals in the ipsilateral principal sensory
      trigeminal nucleus, descending trigeminal nucleus, medial funicular nucleus,
      facial lobe, and medial part of posterior lateral valvular nucleus. The principal
      sensory trigeminal nucleus is considered a major origin of the secondary sensory
      trigeminal projections in teleosts. To investigate the secondary sensory
      trigeminal projections, tracer injections were performed into the principal
      sensory trigeminal nucleus. The present study suggests that the principal sensory
      trigeminal nucleus projects to the bilateral ventromedial thalamic nucleus,
      periventricular pretectal nucleus, stratum album centrale of the optic tectum,
      caudomedial region of lateral preglomerular nucleus, ventrolateral nucleus of
      semicircular torus, medial part of rostral and posterior lateral valvular
      nucleus, oculomotor nucleus, trochlear nucleus, trigeminal motor nucleus, facial
      motor nucleus, superior and inferior reticular formation, descending trigeminal
      nucleus, medial funicular nucleus, inferior olive, and to the contralateral
      sensory trigeminal nucleus. These observations indicate that the primary and
      secondary trigeminal sensory projections of a cyprinid teleost, the carp, are
      similar to those in percomorph teleosts.

PMID- 17029258
TI  - Expression of protein kinase C-substrate mRNAs in the basal ganglia of adult and
      infant macaque monkeys.
AB  - We performed in situ hybridization histochemistry on the monkey basal ganglia to
      investigate the mRNA localization of three protein kinase C substrates (GAP-43,
      MARCKS, and neurogranin), of which expression plays a role in structural changes
      in neurites and synapses. Weak hybridization signals for GAP-43 mRNA and intense
      signals for both MARCKS and neurogranin mRNAs were observed in the adult
      neostriatum. All three of the mRNAs were expressed in both substance P-positive
      direct pathway neurons and enkephalin-positive indirect pathway neurons. In the
      nucleus accumbens, the hybridization signals for the three mRNAs were weaker than
      those in the neostriatum. Double-label in situ hybridization histochemistry in
      the neostriatum revealed that GAP-43 and neurogranin mRNAs were expressed in a
      subset of MARCKS-positive neurons. While intense hybridization signals for MARCKS
      mRNA were observed in all of the other basal ganglia regions such as the globus
      pallidus, substantia innominata, subthalamic nucleus, and substantia nigra,
      intense signals for GAP-43 mRNA were restricted to the substantia innominata and
      substantia nigra pars compacta. No signal for neurogranin mRNA was observed in
      the basal ganglia regions outside the neostriatum and the nucleus accumbens.
      These results indicate that the protein kinase C substrates are abundant in some
      specific connections in cortico-basal ganglia circuits. Developmental analysis
      showed that the expression level in the putamen and nucleus accumbens, but not in
      the caudate nucleus, was higher in the infant than in the adult, suggesting that
      synaptic maturation in the caudate nucleus occurs earlier than that in the
      putamen and nucleus accumbens.

PMID- 17029259
TI  - Longitudinal study of the motor response to levodopa in Parkinson's disease.
AB  - In this prospective study of 34 patients with Parkinson's disease, measurements
      of the short duration levodopa motor response have been performed in defined off
      states at 3 yearly intervals over a mean period of 11.4 years from the point of
      commencement of levodopa treatment. Twenty-two patients were still available for
      study; 10 had died and 2 were lost to follow-up. The levodopa motor response
      amplitude increases over the first 5 years of treatment, and thereafter, on and
      off scores worsen in parallel with conservation of the response. Patients who
      developed motor fluctuations within the first 5 years of treatment had, on
      average, a stronger response to levodopa with significantly better on phase motor
      function (P = 0.003). Although the proportion of "midline" motor disability
      (affecting gait, balance, and cranial motor function) increases with time, these
      deficits do not actually become unresponsive to levodopa. Patients who developed
      dementia had a significantly more rapid decline in motor function. The latest
      graph of serial scores for the whole cohort shows an upward curving or
      exponential increase in motor disability after the first decade of treatment.
      Applying a notional untreated disability line to this graph--an estimate of the
      disability that would have accrued if drugs had never been given--we suggest that
      the long-duration response to levodopa eventually runs down with disease
      progression.

PMID- 17029260
TI  - Hypoperfusion of the auditory and prefrontal cortices in Parkinsonian patients
      with verbal hallucinations.
AB  - We examined patients with and without auditory hallucinations, using n-isopropyl
      p-[123I]iodoamphetamine single photon emission computed tomographic imaging. We
      assessed verbal hallucinations in the present study: patients with nonverbal
      auditory hallucinations were excluded. A total of 11 patients with verbal and
      visual hallucinations and 17 patients with visual hallucinations only were
      enrolled. Patients with both verbal and visual hallucinations revealed
      significant hypoperfusion in the bilateral prefrontal cortex and right superior
      temporal gyrus compared to patients with visual hallucinations only. There were
      no significant hyperperfusion in patients with verbal plus visual hallucinations.
      These results may support the release hallucination theory in verbal
      hallucinations of Parkinson's disease, although another explanations may be more
      appropriate and further studies are required.

PMID- 17029261
TI  - Age at menopause predicts age at onset of Parkinson's disease.
AB  - We investigated the association between age at onset of Parkinson's disease (PD)
      and fertile life characteristics in 145 women. Linear regression analyses showed
      a significant correlation between age at PD onset and age at menopause (P =
      0.003), between age at PD onset and fertile life duration (P = 0.008), and a
      nonsignificant correlation between PD onset and cumulative duration of
      pregnancies (P = 0.23). These results support the possible role of estrogens in
      PD.

PMID- 17029263
TI  - Neurosurgical treatment of tremor in mitochondrial encephalopathy.
AB  - A 53-year-old woman underwent several ischemic stroke-like episodes and later
      developed incomplete, bilateral ophthalmoplegia, left vision deterioration, and
      bilateral tremor. The clinical course, laboratory data, and muscle histology led
      to a diagnosis of mitochondrial encephalomyopathy. No other etiology could be
      identified in the background of her disabling bilateral postural-kinetic tremor.
      As this tremor did not respond to pharmacological therapy, left thalamotomy and
      subsequently right thalamic deep brain stimulator (DBS) implantation were
      performed, which resulted in an excellent clinical outcome. The Fahn-Tolosa-Marin
      Tremor Rating Scale improved from 110 to 11 points. This case suggests that the
      rare tremor caused by mitochondrial encephalopathy may be treated long-term with
      either thalamotomy or thalamic DBS implantation.

PMID- 17029262
TI  - Differential responses to branched and unsaturated aliphatic hydrocarbons in the
      rat olfactory system.
AB  - In an effort to understand mammalian olfactory processing, we have been
      describing the responses to systematically different odorants in the glomerular
      layer of the main olfactory bulb of rats. Previously, we demonstrated
      chemotopically organized and distinct olfactory responses to a homologous series
      of straight-chained alkanes that consisted of purely hydrocarbon structures,
      indicating that hydrocarbon chains could serve as molecular features in the
      combinatorial coding of odorant information. To better understand the processing
      of hydrocarbon odorants, we now have examined responses to other types of
      chemical changes in these kinds of molecules, namely, branching and carbon-carbon
      bond saturation. To this end, we used the [14C]2-deoxyglucose method to determine
      glomerular responses to a group of eight-carbon branched alkane isomers,
      unsaturated octenes (double-bonded), and octynes (triple-bonded). In contrast to
      the differential responses we observed previously for straight-chained alkanes of
      differing carbon number, the rat olfactory system was not particularly sensitive
      to these variations in branching and bond saturation. This result was unexpected,
      given the distinct molecular conformations and property profiles of the odorants.
      The similarity in activity patterns was paralleled by a similarity in spontaneous
      perceptual responses measured using a habituation assay. These results
      demonstrate again the functional relationship between bulbar activity patterns
      and odor perception. The results further suggest that the olfactory system does
      not respond equally to all aspects of odorant chemistry, functioning as a
      specific, rather than a general, chemical analysis system.

PMID- 17029264
TI  - Striatal dopaminergic neurons are lost with Parkinson's disease progression.
AB  - Increased numbers of dopaminergic neurons are described in the striatum of
      patients with Parkinson's disease. In postmortem striatal tissue from Parkinson's
      disease patients with short disease duration (< or =8 years), the number of
      dopaminergic neurons is approximately four times that in patients with long
      duration (> or =16 years). The data suggest the possibility that the presence of
      large numbers of these striatal dopaminergic neurons may be harmful and may
      accelerate the disease process. Alternatively, these neurons may be lost to the
      disease process.

PMID- 17029266
TI  - Cerebral autoregulation is preserved in multiple system atrophy: A transcranial
      Doppler study.
AB  - Patients with multiple system atrophy (MSA) present large changes in blood
      pressure (BP) due to autonomic disturbances. We analyzed how this change may
      influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of
      arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV)
      (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of
      age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to
      oscillations in mean BP was studied in the supine position by cross-spectral
      analysis of mean BP and mean MCA BFV. The DCA was also studied during the
      decrease in BP the first seconds when standing up from a sitting position by the
      assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV
      ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid
      frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active
      autoregulation in response to larger changes in BP. Changes in CR reflecting the
      rate of autoregulation, when standing did not differ between the two groups.
      These data suggest that dynamic cerebral autoregulation is preserved in MSA.

PMID- 17029267
TI  - Patterns of mechanical energy change in tetrapod gait: pendula, springs and work.
AB  - Kinematic and center of mass (CoM) mechanical variables used to define
      terrestrial gaits are compared for various tetrapod species. Kinematic variables
      (limb phase, duty factor) provide important timing information regarding the
      neural control and limb coordination of various gaits. Whereas, mechanical
      variables (potential and kinetic energy relative phase, %Recovery, %Congruity)
      provide insight into the underlying mechanisms that minimize muscle work and the
      metabolic cost of locomotion, and also influence neural control strategies. Two
      basic mechanisms identified by Cavagna et al. (1977. Am J Physiol 233:R243-R261)
      are used broadly by various bipedal and quadrupedal species. During walking,
      animals exchange CoM potential energy (PE) with kinetic energy (KE) via an
      inverted pendulum mechanism to reduce muscle work. During the stance period of
      running (including trotting, hopping and galloping) gaits, animals convert PE and
      KE into elastic strain energy in spring elements of the limbs and trunk and
      regain this energy later during limb support. The bouncing motion of the body on
      the support limb(s) is well represented by a simple mass-spring system. Limb
      spring compliance allows the storage and return of elastic energy to reduce
      muscle work. These two distinct patterns of CoM mechanical energy exchange are
      fairly well correlated with kinematic distinctions of limb movement patterns
      associated with gait change. However, in some cases such correlations can be
      misleading. When running (or trotting) at low speeds many animals lack an aerial
      period and have limb duty factors that exceed 0.5. Rather than interpreting this
      as a change of gait, the underlying mechanics of the body's CoM motion indicate
      no fundamental change in limb movement pattern or CoM dynamics has occurred.
      Nevertheless, the idealized, distinctive patterns of CoM energy fluctuation
      predicted by an inverted pendulum for walking and a bouncing mass spring for
      running are often not clear cut, especially for less cursorial species. When the
      kinematic and mechanical patterns of a broader diversity of quadrupeds and bipeds
      are compared, more complex patterns emerge, indicating that some animals may
      combine walking and running mechanics at intermediate speeds or at very large
      size. These models also ignore energy costs that are likely associated with the
      opposing action of limbs that have overlapping support times during walking. A
      recent model of terrestrial gait (Ruina et al., 2005. J Theor Biol, in press)
      that treats limb contact with the ground in terms of collisional energy loss
      indicates that considerable CoM energy can be conserved simply by matching the
      path of CoM motion perpendicular to limb ground force. This model, coupled with
      the earlier ones of pendular exchange during walking and mass-spring elastic
      energy savings during running, provides compelling argument for the view that the
      legged locomotion of quadrupeds and other terrestrial animals has generally
      evolved to minimize muscle work during steady level movement.

PMID- 17029265
TI  - Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or
      cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic
      vesicular transporter and postsynaptic scaffolding proteins.
AB  - Orexin/hypocretin (Orx) neurons are critical for the maintenance of waking in
      association with behavioral arousal and postural muscle tone, since with their
      loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons
      project to the hypothalamus and play important diverse roles in sleep/wake
      states, we sought to determine whether acetylcholine (ACh), glutamate (Glu),
      and/or GABA-releasing BF neurons innervate and could thereby differentially
      regulate the Orx neurons. From discrete injections of biotinylated dextran amine
      (BDA, 10,000 MW) into the magnocellular preoptic nucleus (MCPO) and substantia
      innominata (SI) in the rat, BDA-labeled fibers projected to the lateral
      hypothalamus (LH), perifornical area (PF), and dorsomedial hypothalamus (DMH),
      where approximately 41%, approximately 11%, and 9% of Orx-positive (+) neurons
      were respectively contacted in each region. Employing triple fluorescent staining
      for Orx, BDA, and presynaptic vesicular (V) transporters (T), we found that only
      4% of the innervated Orx+ neurons in the LH were contacted by BDA+[VAChT+]
      terminals, whereas approximately 31% and approximately 67% were respectively
      contacted by BDA+[VGluT2+] and BDA+[VGAT+] terminals. In 3D-rendered and rotated
      confocal images, we confirmed the latter contacts and examined staining for
      postsynaptic proteins PSD-95, a marker for glutamatergic synapses, and gephyrin,
      a marker for GABAergic synapses, that were located on Orx+ neurons facing BDA
      labeled terminals in approximately 20% and approximately 50% of contacts,
      respectively. With such synaptic input, BF glutamatergic neurons can excite Orx
      neurons and thus act to maintain behavioral arousal with muscle tone, whereas
      GABAergic neurons can inhibit Orx neurons and thus promote behavioral quiescence
      and sleep along with muscle atonia.

PMID- 17029268
TI  - The tri-segmented limbs of therian mammals: kinematics, dynamics, and self
      stabilization--a review.
AB  - The evolution of therian mammals is to a large degree marked by changes in their
      motion systems. One of the decisive transitions has been from the sprawled, bi
      segmented to the parasagittal, tri-segmented limb. Here, we review aspects of the
      tri-segmented limb in locomotion which have been elucidated in our research
      groups in the last 10 years. First, we report the kinematics of the tri-segmented
      therian limb from mouse to elephant in order to explore general principles of the
      therian limb configuration and locomotion. Torques will be reported from a
      previous paper (Witte et al., 2002. J Exp Biol 205:1339-1353) for a better
      understanding of the anti-gravity work of all limb joints. The stability of a
      limb in z-configuration will be explained and its advantage with respect to other
      potential solutions from modeling will be discussed. Finally, we describe how the
      emerging concept of self-stability can be explained for a tri-segmented leg
      template and how it affects the design of the musculoskeletal system and the
      operation of legs during locomotion. While locomotion has been considered as
      mainly a control problem in various disciplines, we stress the necessity to
      reduce control as much as possible. Central control can be cheap if the limbs are
      "intelligent" by means of their design. Gravity-induced movements and self
      stability seem to be energy-saving mechanisms.

PMID- 17029269
TI  - Correlation of symmetrical gaits and whole body mechanics: debunking myths in
      locomotor biodynamics.
AB  - Independent maturation of gait (Hildebrand) and whole body mechanics (Cavagna et
      al.) traditions in locomotor analyses has led to conflicting terminology. Re
      evaluation of these traditions yields three primary insights. First, walking and
      running should be recognized by their fundamentally different mechanics. Because
      duty factor fails to consistently distinguish these mechanics, its use in
      discriminating walks from runs should be abandoned in preference to parameters
      that more accurately reflect the movements of the center of mass (COM; phase
      difference in external mechanical energy or Froude number). Second, "trot" should
      be reserved as a descriptor of a particular footfall pattern. This and all gait
      terms lack explicit information about limb compliance and thus COM movements.
      Third, symmetrical gait definitions should be broadened to reflect the four
      primary footfall patterns: the lateral-couplet dominated pattern of the pace, the
      diagonal-couplet dominated pattern of the trot and the more independent
      sequencing of footfalls of the two singlefoots. Intermediate gaits (perennially
      confusing and a mouthful to pronounce) are thereby subsumed by these four
      discrete gaits. Confusion between gait terminologies would be avoided if limb
      phase were consistently reported.

PMID- 17029270
TI  - Periventricular efferent neurons in the optic tectum of rainbow trout.
AB  - The efferent connections and axonal and dendritic morphologies of periventricular
      neurons were examined in the optic tectum of rainbow trout to classify
      periventricular efferent neurons in salmonids. Among the target nuclei of tectal
      efferents, tracer injections to the following four structures labeled
      periventricular neurons: the area pretectalis pars dorsalis (APd), nucleus
      pretectalis superficialis pars magnocellularis (PSm), nucleus ventrolateralis of
      torus semicircularis (TS), and nucleus isthmi (NI). Two types of periventricular
      neurons were labeled by injections to the APd. One of them had an apical dendrite
      ramifying at the stratum fibrosum et griseum superficiale (SFGS), with an axon
      that bifurcated into two branches at the stratum griseum centrale (SGC), and the
      other had an apical dendrite ramifying at the SGC. Two types of periventricular
      neurons were labeled after injections to the TS. One of them had an apical
      dendrite ramifying at the boundary between the stratum opticum (SO) and the SFGS,
      and the other had dendritic branches restricted to the stratum album centrale or
      stratum periventriculare. Injections to the PSm and NI labeled periventricular
      neurons of the same type with an apical dendrite ramifying at the SO and a
      characteristic axon that split into superficial and deep branches projecting to
      the PSm and NI, respectively. This cell type also possessed axonal branches that
      terminated within the tectum. These results indicate that periventricular
      efferent neurons can be classified into at least five types that possess type
      specific axonal and dendritic morphologies. We also describe other tectal neurons
      labeled by the present injections.

PMID- 17029271
TI  - Distribution and differentiation of microglia in the human encephalon during the
      first two trimesters of gestation.
AB  - We describe the topographical distribution of microglial subpopulations during
      development of the human diencephalon and telencephalon. Brains from embryos and
      fetuses age 5-23.5 gestational weeks (gw) were subjected to single- and double
      immunolabeling for lectin RCA-1 (Ricinus Communis Agglutinin 1), Iba1 (a
      microglial marker), CD68 (specific of macrophages), CD45 (marker for mononucleate
      cells of hematopoietic lineage), CD34 (expressed on endothelial cells), and MIB1
      and Ki67 (markers for cell proliferation). At 5.5 gw the first intracerebral
      microglial cells were seen close to the meninges and choroid plexus near the di
      telencephalic fissure. They were amoeboid and positive for Iba1, CD45, and RCA-1,
      whereas cells in the deep parenchyma expressed Iba1/CD68/RCA-1 and constituted
      clusters. In the developing diencephalon, microglial clusters were located in
      junctional regions of the white matter anlagen, most notably at the junctions of
      the internal capsule with the thalamic projections, the external capsule, and the
      cerebral peduncle. In the cortical anlagen, Iba1+/RCA-1/CD68+/CD45+ cells
      accumulated at 10-12 gw, constituting a tangential band at the junction between
      the cortical plate and the subplate. Between 10 and 16 gw microglial clusters
      increased markedly in size and cellular density. Contact between Iba1+ microglia
      and CD34+ blood vessels was clearly visible from 10-12 gw onward, first in
      microglial clusters of the white matter anlagen and subsequently throughout the
      parenchyma. From the middle of the second trimester onward microglial cells
      colonized the entire cerebral parenchyma, developed a ramified morphology, and
      downregulated their surface antigens, but remained more numerous in the white
      matter.

PMID- 17029272
TI  - Hypoperfusion of the visual pathway in parkinsonian patients with visual
      hallucinations.
AB  - Little is known about the developing mechanisms of visual hallucinations in
      Parkinson's disease. This study aimed to investigate perfusion changes in
      parkinsonian patients with visual hallucinations using n-isopropyl-p
      [123I]iodoamphetamine ([123I]IMP) single photon emission computed tomography
      imaging. A total of 70 consecutive patients, including 31 patients with visual
      hallucinations, and 39 patients without hallucinations, participated in this
      study. Patients with severe cognitive impairment (Mini-Mental State Examination
      score < 20), nonvisual hallucinations, or confusion were excluded. We compared
      brain perfusion changes between the two groups. We found that hallucinatory
      patients had significant perfusion reductions in the bilateral inferior parietal
      lobule, inferior temporal gyrus, precuneus gyrus, and occipital cortex compared
      to nonhallucinatory patients. These results suggested that hypoperfusion of the
      visual pathway was closely related to visual hallucinations in Parkinson's
      disease.

PMID- 17029273
TI  - Associations between family history of Parkinson's disease and dementia and risk
      of dementia in Parkinson's disease: A community-based, longitudinal study.
AB  - Dementia is common in patients with Parkinson's disease (PDD). The etiology of
      PDD is still unclear, but exciting advances have been made in discovering
      pathogenetic components in Parkinson's disease (PD), implicating the role of
      genetic factors. It is, however, still controversial whether genetic factors also
      contribute to the development of dementia in PD. Thus, we investigated the
      association between development of dementia and a positive family history of PD
      or dementia in a community-based study of PD in Rogaland County, Norway (n =
      219). The patients were followed prospectively with neurological and
      neuropsychological assessments. Dementia was more common in patients with a
      strong family association of PD (first-degree relatives > second-degree relatives
      > no family history; P < 0.05). However, time to dementia did not differ between
      the two groups. No associations between dementia in PD and familial occurrence of
      dementia could be shown. Further studies with larger samples are needed to
      explore a possible relationship between a family history of PD and development of
      dementia in PD and its potential pathogenetic mechanisms.

PMID- 17029274
TI  - Measures of dyspnea in patients with amyotrophic lateral sclerosis.
AB  - Respiratory symptoms are not well characterized in amyotrophic lateral sclerosis
      (ALS). The baseline dyspnea index (BDI) and transition dyspnea index (TDI) are
      indices designed to measure change in dyspnea over time. They are easy to
      administer and do not inquire about specific physical tasks. The latter makes
      these scales particularly well suited for use in ALS. This study evaluated the
      ability of the BDI and TDI to measure dyspnea in 46 subjects with ALS. The
      BDI/TDI had excellent reproducibility. The TDI detected worsening dyspnea by 4
      weeks and declined significantly more over the subsequent 8 weeks. The TDI was
      significantly associated with changes in forced vital capacity and appeared more
      sensitive to changes in dyspnea than the ALS functional rating scale-respiratory
      subscale (ALS-FRS R) and a visual analog scale of breathlessness. The BDI and TDI
      thus appear to be useful measures in ALS and may have both clinical and research
      applications.

PMID- 17029275
TI  - Long-term outcome of hematuria home screening for bladder cancer in men.
AB  - BACKGROUND: The objectives of this study were to determine whether bladder cancer
      (BC) screening in healthy men could lead to earlier detection and reduced BC
      mortality compared with unscreened men and to determine long-term outcomes of a
      geographically defined, unscreened population with newly diagnosed BC. METHODS:
      In 1987 and from 1998 to 1992, 1575 men ages 50 years and older who were
      solicited from well patient rosters in clinics in and around Madison, Wisconsin,
      tested their urine repetitively with a chemical reagent strip for hemoglobin.
      Participants who had positive test results underwent standard urologic
      evaluation. BC grades and stages and the outcomes of men with BC detected by
      screening were compared with the grades, stages, and outcomes of 87% of men ages
      50 years and older with newly diagnosed BC who were reported to the Wisconsin
      Tumor Registry in 1988 (n = 509 men). RESULTS: Two hundred fifty-eight screening
      participants (16.4%) were evaluated for hematuria, and 21 participants (8.1%)
      were diagnosed with BC. Proportions of low-grade (Grade 1 and 2) superficial
      (Stage Ta and T1) versus high-grade (Grade 3) superficial or invasive (Stage > or
      = T2) cancers in screened men (52.4% vs. 47.7%) and in men from the tumor
      registry (60.3% vs. 39.7%) were similar (P = .50). The proportion of high-grade
      superficial or invasive BCs that were invasive were lower in screened men (10%)
      than in unscreened men (60%; P = .002). At 14 years of follow-up, no men with
      screen-detected BC had died of BC, whereas 20.4% of men with unscreened BC had
      died of BC (P = .02). CONCLUSIONS: Screening effected the early detection of BC
      and may reduce mortality from BC compared with BC that is diagnosed at standard
      clinical presentation.

PMID- 17029276
TI  - Improved tolerability and quality of life with maintained efficacy using twice
      daily low-dose interferon-alpha-2b: results of a randomized phase II trial of low
      dose versus intermediate-dose interferon-alpha-2b in patients with metastatic
      renal cell carcinoma.
AB  - BACKGROUND: In vivo data have shown a more potent antiangiogenic effect and a
      higher antitumor activity of low-dose interferon (IFN) given twice daily. In a
      randomized Phase II trial, the authors tested the hypothesis that twice-daily low
      dose IFN is more effective than daily intermediate-dose IFN in patients with
      metastatic renal cell cancer (MRCC). METHODS: A total of 118 patients (59 per
      arm) were randomly assigned to receive IFN at a dose of 0.5 million units (MU)
      given subcutaneously twice daily (IFN1) or IFN at a dose of 5 MU given
      subcutaneously daily (IFN5). The primary endpoint was progression-free survival
      (PFS). Secondary endpoints included response rate (RR), overall survival (OS),
      toxicity, and quality of life (QOL). RESULTS: There were no significant
      differences in either PFS or OS between IFN1 and IFN5 (median of 3.7 months and
      median of 3.4 months PFS, respectively; median of 25.5 months and median of 17.5
      months OS, respectively). The RRs were identical in the 2 arms (6.7%; 95%
      confidence interval [95% CI], 1.8-16.5%). Two patients, 1 in each arm, remained
      in complete remission at the time of last follow-up, at 45+ and 38+ months from
      treatment. Thirty-two patients receiving IFN5 and 19 patients receiving IFN1
      experienced Grade 3 or higher adverse events (graded using the National Cancer
      Institute Common Toxicity Criteria [version 2.0]) (P = .025). Eighteen patients
      receiving IFN5 and 4 patients receiving IFN1 had dose reductions (P = .002).
      There was a significant deterioration in QOL and an increase in depression
      associated with IFN5 but no change was noted with IFN1. CONCLUSIONS: Compared
      with IFN5, IFN1 is neither more nor less effective but is less toxic, with a
      better reported QOL. These results may have implications for the design of
      combination regimens incorporating IFN with targeted agents.

PMID- 17029277
TI  - Stability, limb coordination and substrate type: the ecorelevance of gait
      sequence pattern in primates.
AB  - The coordination of limb movements during mammalian locomotion has been well
      documented in the literature. Most mammals use lateral sequence (LS) gaits, in
      which a forelimb follows an ipsilateral hind limb during the stride cycle.
      Primates, however, tend to utilize diagonal sequence (DS) gaits, whereby a
      contralateral forelimb follows a given hind limb during the stride cycle. A
      number of scenarios have been offered to explain why primates favor DS gaits,
      most of them relating to the use of the arboreal habitat and, in particular, the
      exploitation of a terminal branch niche. Yet to date, there is surprisingly
      little evidence to support the advantage of DS gaits for negotiating different
      aspects of the terminal branch environment. Nonetheless, it is apparent that
      primates possess unique morphologies and a higher than typically recognized
      degree of flexibility in gait sequence pattern, both of which likely offer
      advantages for moving upon discontinuous and unstable terminal branches. This
      paper reviews potential explanations for the use of DS gaits in primates and
      considers mechanisms by which gait sequence may be altered during different types
      of arboreal challenges.

PMID- 17029278
TI  - Botulinum toxin and neuromotor rehabilitation: An integrated approach to
      idiopathic cervical dystonia.
AB  - Currently, the best treatment option for idiopathic cervical dystonia (ICD) is
      injection of botulinum toxin (BTX) into the affected muscles, whereas
      rehabilitative approaches have given disappointing results. We evaluated whether
      the association of an ad hoc rehabilitative program may improve the clinical
      efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty
      patients with ICD were randomly assigned to two different treatment groups: (1)
      BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2)
      BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the
      clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at
      reinjection (284.5 vs. 325.5 units). In addition, they showed more marked
      reductions in their disability in activities of daily living (-9.7 vs. -4.85
      points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A
      therapy with a specific program of physical therapy may improve ICD treatment
      outcome.

PMID- 17029279
TI  - Cost savings associated with the use of fine-needle aspiration biopsy (FNAB) for
      the diagnosis of palpable masses in a community hospital-based FNAB clinic.
AB  - BACKGROUND: Generally, it is assumed that fine-needle aspiration biopsy (FNAB)
      for the diagnosis of superficial, palpable masses is a less expensive alternative
      to diagnostic open surgical biopsy; however, to the authors' knowledge few
      studies to date have sought to quantify the number of diagnostic surgical
      procedures avoided and cost savings involved. In this article, the authors report
      their experience with 664 FNAB procedures that were performed by a
      cytopathologist/cytotechnologist team practicing in a community setting. METHODS:
      Records from a total of 664 consecutive FNAB cases from 607 patients who
      underwent FNAB in a community hospital-based FNAB clinic between 2003 and 2005
      were reviewed retrospectively, and follow-up data were obtained. RESULTS: Surgery
      was averted entirely as a result of the FNAB in 83% or 505 of 609 cases with
      follow-up available. The FNAB procedure was highly accurate and considerably less
      expensive than surgical biopsy. CONCLUSION: For patients who presented with
      palpable masses, FNAB was a reliable, cost-effective initial method for obtaining
      a tissue diagnosis.

PMID- 17029280
TI  - Identification of high-grade cervical dysplasia by the detection of p16INK4a in
      cell lysates obtained from cervical samples.
AB  - BACKGROUND: Current cervical cancer screening approaches are based on cytology
      supplemented by human papillomavirus (HPV) testing in some settings. Whereas
      cytology is laborious and depends on the cytologists' experience, HPV testing has
      limited specificity when it is used to detect high-grade lesions. A dichotomous
      test to identify high-grade lesions with greater specificity may be a useful tool
      for cervical cancer screening. p16(INK4a) is a cell-cycle regulator that has
      demonstrated strong overexpression in cervical precancer cells and cervical
      cancer induced by the deregulated expression of HPV oncogenes. METHODS: The
      authors used a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify the
      amount of solubilized p16(INK4a) protein in lysates that were prepared from
      cervical samples to detect high-grade cervical lesions. In total, 187 specimens
      that were obtained after sampling for conventional cytology in women who attended
      a cervical colposcopy clinic were analyzed. Seventy-six women underwent a biopsy,
      and 45 of those women showed histologically confirmed, high-grade cervical
      intraepithelial neoplasia. RESULTS: For 76 women with biopsy-proven diagnoses,
      receiver operating characteristic (ROC) analysis of different cutoff values
      showed an area under the ROC curve of 0.89 for the detection of high-grade
      cervical dysplasia. At a cutoff value of 8 U/mL, the sensitivity of the
      p16(INK4a) ELISA for detecting high-grade dysplastic cervical lesions was 96%.
      CONCLUSIONS: The data obtained in this study suggested that ELISA-based
      quantification of solubilized p16(INK4a) protein may have high sensitivity for
      detecting cervical precancer. Further population-based studies will be necessary
      to analyze the specificity and predictive values of p16(INK4a) protein
      quantification in cervical samples.

PMID- 17029281
TI  - What are the relations between mechanics, gait parameters, and energetics in
      terrestrial locomotion?
AB  - Are the different energy-conserving mechanics (i.e., pendulum and spring) used in
      different gaits reflected in differences in energetics and/or stride parameters?
      The analysis included published data from several species and new data from
      horses. When changing from pendulum to spring mechanics, there is a change in the
      slope of metabolic rate (MR) vs. speed in all species, in birds and quadrupeds
      there is no step increase, and in humans there are conflicting reports. At the
      trot-gallop transition, where quadrupeds are hypothesized to change from spring
      mechanics to some combination of spring and pendulum mechanics, there is a change
      in slope of MR vs. speed in horses but not in other species. Stride frequency
      (SF) is a logarithmic function of walking speed in all species, a linear function
      of trotting/running speed, and nearly independent of speed in galloping. In
      humans and horses there is a discontinuity in SF at the walk-trot (run)
      transition but not in birds. The slope of time of contact vs. speed does not
      change with mechanics in most species, but it does in humans. In horses and
      humans, there is a discontinuity at the walk-trot (run) transition and data for
      other species do not permit generalization. Duty factor (DF) in humans is greater
      than 0.5 in walking (pendulum mechanics) and less than 0.5 when running (spring
      mechanics). However, this is not true in many species that have DF>0.5 at the
      lowest speeds where they use spring mechanics. When trotting at low speeds,
      horses use forelimb DF>0.5 and hind limb DF<0.5. Thus, it is confusing to
      distinguish between walking and running by DF.

PMID- 17029282
TI  - De novo nonalcoholic fatty liver disease after liver transplantation.
AB  - Hepatic steatosis is a recognized problem in patients after orthotopic liver
      transplant (OLT). However, de novo development of nonalcoholic fatty liver
      disease (NAFLD) has not been well described. The aim of this study was to
      determine the prevalence and predictors of de novo NAFLD after OLT. A
      retrospective analysis was performed on 68 OLT patients with donor liver biopsies
      and posttransplantation liver biopsies. Individual medical charts were reviewed
      for demographics, indication for OLT, serial histology reports, genotypes for
      hepatitis C, comorbid conditions, and medications. Liver biopsies were reviewed
      blindly and graded according to the Brunt Scoring System. Multivariate logistic
      regression analysis was used to study the risk factors for developing NAFLD. The
      interval time from OLT to subsequent follow-up liver biopsy was 28 +/- 18 months.
      A total of 12 patients (18%) developed de novo NAFLD, and 6 (9%) developed de
      novo NASH. The regression model indicated that the use of angiotensin-converting
      enzyme inhibitors (ACE-I) was associated with a reduced risk of developing NAFLD
      after OLT (odds ratio, 0.09; 95% confidence interval, 0.010-0.92; P = 0.042).
      Increase in body mass index (BMI) of greater than 10% after OLT was associated
      with a higher risk of developing NAFLD (odds ratio, 19.38; 95% confidence
      interval, 3.50-107.40; P = 0.001). In conclusion, de novo NAFLD is common in the
      post-OLT setting, with a significant association with weight gain after
      transplant. The use of an ACE-I may reduce the risk of developing post-OLT NAFLD.

PMID- 17029283
TI  - Use of split-liver allografts does not impair pediatric recipient growth.
AB  - The use of split-liver (SL) allografts continues to be an excellent option for
      many pediatric recipients. Patient and graft survival with this graft type are
      comparable to patient and graft survival with whole organ grafts. Quality-of-life
      issues, specifically growth, for SL recipients have not been compared to those of
      recipients of more conventional whole-organ recipients. Pediatric recipients of
      SL and whole allografts at 2 institutions were identified. Height, z score, and
      delta z score were calculated for all recipients for each year after transplant.
      Between 1995 and 2004, 201 pediatric liver transplants were analyzed. Data were
      collected on 39 split-graft recipients and 36 whole-size recipients. Only
      subjects 3 years or younger were included in the study. Growth retardation was
      present in all recipients at transplant. Height z score post split and whole-size
      transplant were not statistically different at 1- (P = 0.65), 2- (P = 0.13), and
      3-year (P = 0.32) anniversaries, respectively. Catch-up growth was present only
      in recipients of split grafts. In conclusion, the use of split grafts as opposed
      to whole-size grafts revealed no significant differences in terms of linear
      growth. Our report indicates that split-liver transplantation does not impair
      recipient growth.

PMID- 17029284
TI  - Transthyretin-derived amyloid deposition on the gastric mucosa in domino
      recipients of familial amyloid polyneuropathy liver.
AB  - Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized
      amyloidosis. Liver tissue explanted from FAP patients has normal structure and
      function, except for the production of amyloidogenic variant transthyretin (TTR),
      and domino liver transplantation (DLT) using grafts from FAP patients was first
      performed in 1995. FAP symptoms usually develop in genetically determined
      individuals after the age of 20, but it is difficult to estimate when FAP
      symptoms will appear in domino recipients. Concerning this problem, histological
      findings showing amyloid deposition have recently been obtained in a few domino
      recipients of FAP livers. This study investigated the presence of de novo amyloid
      deposition in the gastroduodenal mucosa of domino recipients transplanted at our
      institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of
      FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of
      whom had undergone DLT 47 months previously. In FAP liver recipients, de novo
      systemic amyloid deposition may begin much sooner than previously supposed.
      Therefore, careful follow-up of domino recipients of FAP livers is required.

PMID- 17029285
TI  - Satellite cells express distinct patterns of myogenic proteins in immature
      skeletal muscle.
AB  - Satellite cells are the myogenic cells lying between the myofiber sarcolemma and
      basal lamina. The objective of this study was to determine the expression
      patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the
      growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the
      expression of the myogenic markers was also studied within the interstitial cell
      compartment and myonuclei. It was discovered that the soleus contained a higher
      number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL.
      Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus
      compared with the EDL, and myogenin was expressed at a higher level in the
      interstitial compartment of the soleus compared with the EDL. When interstitial
      nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the
      satellite cell population, it was discovered that approximately of 13% of the
      myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers
      exhibit a labeled satellite cell nucleus. Overall, results from this study
      suggest that expression patterns of these markers vary predictably among muscles
      with different growth dynamics and phenotypic characteristics.

PMID- 17029286
TI  - Neural stem cells for the treatment of disorders of the enteric nervous system:
      strategies and challenges.
AB  - The main goal of this review is to summarize the status of the research in the
      field of stem cells transplantation, as it is applicable to the treatment of
      gastrointestinal motility. This field of research has advanced tremendously in
      the past 10 years, and recent data produced in our laboratories as well as others
      is contributing to the excitement on the use of neural stem cells (NSC) as a
      valuable therapeutic approach for disorders of the enteric nervous system
      characterized by a loss of critical neuronal subpopulations. There are several
      sources of NSC, and here we describe therapeutic strategies for NSC
      transplantation in the gut. These include using NSC as a relatively nonspecific
      cellular replacement strategy in conditions where large populations of neurons or
      their subsets are missing or destroyed. As with many other recent "breakthroughs"
      stem cell therapy may eventually prove to be overrated. However, at the present
      time, it does appear to provide the hope for a true cure for many currently
      intractable diseases of both the central and the peripheral nervous system.
      Certainly more extensive research is needed in this field. We hope that our
      review will encourage new investigators in entering this field of research ad
      contribute to our knowledge of the potentials of NSC and other cells for the
      treatment of gastrointestinal dysmotility.

PMID- 17029287
TI  - Mes2, a MADF-containing transcription factor essential for Drosophila
      development.
AB  - The development of the Drosophila mesoderm is initiated by the basic helix-loop
      helix transcription factor twist. We identified a gene encoding a putative
      transcription factor, mes2, in a screen for essential mesoderm-expressed genes
      that function downstream of twist. Mes2 protein belongs to a family of 48
      Drosophila proteins containing MADF domains. MADF domains exist in worms, flies,
      and fish. Mes2 is a nuclear protein first produced in trunk and head mesoderm
      during late gastrulation. At later embryonic stages, mes2 is expressed in glia of
      the central and peripheral nervous systems, and in tissues derived from the head
      mesoderm. We have identified a null mutation of mes2 that leads to developmental
      arrest in first instar larvae. Increased production of Mes2 in multiple embryonic
      and larval tissues almost always causes lethality. The ubiquitous or epidermal
      misexpression of mes2 in the embryo causes a dramatic loss of epidermal integrity
      resulting in the failure of dorsal closure. Our data show that the precise
      regulation of mes2 expression is critical for normal development in Drosophila
      and implicate Mes2 in the regulation of essential target genes.

PMID- 17029288
TI  - Two-dimensional morphogen gradient in Xenopus: boundary formation and real-time
      transduction response.
AB  - Morphogen gradients play an important role in pattern formation in embryo.
      However, the interpretation of position in a morphogen gradient is not well
      understood. Because it is hard to analyze morphogen gradients especially in
      opaque embryos such as those of Xenopus, it is necessary to fix and section the
      embryo, thereby eliminating the possibility of real-time observation, and making
      more difficult the interpretation of events that take place in three dimensions.
      We describe here a two-dimensional preparation of cells from a Xenopus blastula
      animal cap, in which an activin concentration gradient appears to be formed and
      interpreted at the same rate and in the same way as in normal embryos. We use two
      dimensional preparations of this kind to contribute the following new information
      about gradient formation and interpretation in embryo. We determine the dynamics
      of formation of an activin activity gradient in real time. We demonstrate that
      this gradient is established by diffusion of activin through intercellular space
      and does not require internalization of receptor or ligand. We also show that the
      generation of a boundary of gene expression depends on the interpretation, rather
      than a change of composition, of the concentration gradient.

PMID- 17029289
TI  - Trends of selected malformations in relation to folic acid recommendations and
      fortification: an international assessment.
AB  - BACKGROUND: Two crucial issues relative to the benefits and impact of folic acid
      in the prevention of birth defects are whether supplementation recommendations
      alone, without fortification, are effective in reducing the population-wide rates
      of neural tube defects (NTDs), and whether such policies can reduce the
      occurrence of other birth defects. Using data from 15 registries, we assessed
      rates and trends of 14 major defects, including NTDs, in areas with official
      recommendations or fortification to assess the effectiveness of recommendations
      and fortification on a wide range of major birth defects. METHODS: We evaluated
      surveillance data through 2003 on major birth defects from population-based
      registries from Europe, North America, and Australia. All included ascertainment
      of pregnancy terminations (where legal). Trends before and after policies or
      fortification were assessed via Poisson regression and were compared via rate
      ratios. RESULTS: Significant changes in trends were seen for NTDs in areas with
      fortification but not in areas with supplementation recommendations alone. For
      other major birth defects, there was an overall lack of major trend changes after
      recommendations or fortification. However, some significant declines were
      observed for select birth defects in individual areas. CONCLUSIONS:
      Recommendations alone remain an ineffective approach in translating the known
      protective effect of folic acid in population-wide decline in NTD rates.
      Fortification appears to be effective in reducing NTDs. The effect on other birth
      defects remains unclear.

PMID- 17029290
TI  - The M3/M4 cytoplasmic loop of the alpha1 subunit restricts GABAARs lateral
      mobility: a study using fluorescence recovery after photobleaching.
AB  - A crucial problem in neurobiology is how neurons are able to maintain
      neurotransmitter receptors at specific membrane domains. The large structural
      heterogeneity of gamma aminobutyric acid receptors (GABAARs) led to the
      hypothesis that there could be a link between GABAAR gene diversity and the
      targeting properties of the receptor complex. Previous studies using Fluorescence
      Recovery After Photobleaching (FRAP) have shown a restricted mobility in GABAARs
      containing the alpha1 subunit. The M3/M4 cytoplasmic loop is the region of the
      alpha1 subunit with the lowest sequence homology to other subunits. Therefore, we
      asked whether the M3/M4 loop is involved in cytoskeletal anchoring and GABAAR
      clustering. A series of alpha1 chimeric subunits was constructed: alpha1CH
      (control subunit), alpha1CD (Cytoplasmic loop deleted), alpha1CD2, and alpha1CD3
      (alpha1 with the M3/M4 loop from the alpha2 and alpha3 subunits, respectively).
      Our results using FRAP indicate an involvement of the M3/M4 cytoplasmic loop of
      the alpha1 subunit in controlling receptor lateral mobility. On the other hand,
      inmunocytochemical approaches showed that this domain is not involved in subunit
      targeting to the cell surface, subunit-subunit assembly, or receptor aggregation.

PMID- 17029291
TI  - Myosin16b: The COOH-tail region directs localization to the nucleus and
      overexpression delays S-phase progression.
AB  - Rat Myo16a and Myo16b comprise the founding members of class XVI myosin and are
      characterized by an N-terminal ankyrin repeat domain thought to mediate an
      association with protein phosphatase 1 catalytic subunits 1alpha and 1gamma.
      Myo16b is the principal isoform and reveals predominant expression in developing
      neural tissue. Here, we use COS-7 cells as a model system to develop an
      understanding of Myo16b function. We find that Myo16b displays predominant
      localization in the nucleus of cells transitioning through interphase, but is not
      associated with processes of mitosis. Using a panel of EGFP-Myo16b-expression
      plasmids in transient transfection studies, we identified the COOH-terminal
      residues 1616-1912 as necessary and solely sufficient to target Myo16b to the
      nucleus. We show that the Myo16b-tail region directs localization to a nuclear
      compartment containing profilin and polymerized actin, which appears to form a
      three-dimensional meshwork through the depth of the nucleus. Further, we
      demonstrate that this compartment localizes within euchromatic regions of the
      genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both
      markers of S-phase of the cell cycle. Cells transiently expressing Myo16b or
      Myo16b-tail region show limited incorporation of BrdU, delayed progression
      through S-phase of the cell cycle, and curtailed cellular proliferation.

PMID- 17029292
TI  - Macrophages promote collagen fibrillogenesis around terminal end buds of the
      developing mammary gland.
AB  - Development of the ductal network in the mammary gland is dependent in part on
      the presence of macrophages. Here we utilize multi-photon microscopy and second
      harmonic generation to describe terminal end bud 3-dimensional structure and the
      organization of the surrounding collagen matrix. We have applied this approach to
      analyze the effect of macrophage deficiency on terminal end bud structure and
      collagen organization, using mice homozygous for a null mutation in the colony
      stimulating factor-1 gene (Csf1op/Csf1op). Primary terminal end buds have an
      oblong shape, with long collagen I fibers close to the neck of the terminal end
      bud and radiating upwards in the direction of growth. Around the terminal end
      buds, the amount of total collagen I detected by antibody staining was not
      affected by macrophage deficiency. However the amount of collagen I organized
      into long fibers, detected by second harmonic generation signal, was reduced in
      Csf1op/Csf1op mice. Macrophage deficiency also caused terminal end buds to be
      rounder and shorter. These studies reveal a role for macrophages in collagen
      fibrillogenesis and in organization of the structure of terminal end buds.

PMID- 17029293
TI  - Expression of connexins 36, 43, and 45 during postnatal development of the mouse
      retina.
AB  - Gap junction channels formed by connexins (Cx) may play essential roles in some
      processes that occur during retinal development, such as apoptosis and calcium
      wave spread. The present study was undertaken to determine the distribution
      pattern of Cx36, Cx43, and Cx45 by immunofluorescence, as well as their gene
      expression levels by quantitative PCR during postnatal development of the mouse
      retina. Our results showed an increased expression of neuronal Cx36 from P1 until
      P10, when this Cx reached adult levels, and it was mainly distributed in the
      outer and inner plexiform layers. In turn, Cx43 was almost absent in retinal
      progenitor cells at P1, it became more prominent in glial cell processes about
      P10, and did not change until adulthood. Double-labeling studies in situ and in
      vitro with antivimentin, a Muller cell marker, confirmed that Cx43 was expressed
      by these cells. In addition, quantitative PCR showed that Cx43 and vimentin
      shared very similar temporal expression patterns. Finally, in contrast to Cx36
      and Cx43, Cx45 mRNA was strongly down-regulated during development. In early
      postnatal days, Cx45 was seen ubiquitously distributed throughout the retina in
      cells undergoing proliferation and differentiation, as well in differentiated
      neurons. In adult retina, this protein had a more restricted distribution both in
      neurons and glial cells, as confirmed in situ and in vitro. In conclusion, we
      observed a distinct temporal expression pattern for Cx36, Cx43, and Cx45, which
      is probably related to particular roles in retinal function and maintenance of
      homeostasis during development of the mouse retina.

PMID- 17029294
TI  - ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve
      development.
AB  - Genetic mutations in minor fibrillar collagen types Va1 (ColVa1) and XIa1 (ColXI)
      have been identified in connective tissue disorders including Ehlers-Danlos
      syndrome and chondrodysplasias. ColVa1+/- and ColXIa1-/- mutant mice recapitulate
      these human disorders and show aberrations in collagen fiber organization in
      connective tissue of the skin, cornea, cartilage, and tendon. In the heart,
      fibrous networks of collagen fibers form throughout the ventricular myocardium
      and heart valves, and alterations in collagen fiber homeostasis are apparent in
      many forms of cardiac disease associated with myocardial dysfunction and valvular
      insufficiency. There is increasing evidence for cardiac dysfunction in connective
      tissue disorders, but the mechanisms have not been addressed. ColVa1+/- and
      ColXIa1-/- mutant mice were used to identify roles for ColVa1 and ColXIa1 in
      ventricular myocardial morphogenesis and heart valve development. These affected
      cardiac structures show a compensatory increase in type I collagen deposition,
      similar to that previously described in valvular and cardiomyopathic disease.
      Morphological cardiac defects associated with changes in collagen fiber
      homeostasis identified in ColVa1+/- and ColXIa1-/- mice provide an insight into
      previously unappreciated forms of cardiac dysfunction associated with connective
      tissue disorders.

PMID- 17029295
TI  - The production of (R)-2-hydroxy-1-phenyl-propan-1-one derivatives by benzaldehyde
      lyase from Pseudomonas fluorescens in a continuously operated membrane reactor.
AB  - Benzaldehyde lyase (BAL; E.C. 4.1.2.38) from Pseudomonas fluorescens Biovar I
      catalyzes the reversible formation of benzoins from aromatic aldehydes, and,
      moreover, the coupling of aromatic with aliphatic aldehydes yielding derivatives
      of (R)-2-hydroxy-1-phenyl- propan-1-one (R)-HPPs), which are important chiral
      building blocks. In this paper, we report on the development of a reactor system
      that allows the selective production of substituted (R)-HPP-derivatives. The
      reaction systems yielding (R)-1-(3-chloro-phenyl)-2-hydroxy- propan-1-one, (R)-2
      hydroxy-3-methoxy-1-(4-methoxy-phenyl)-propan-1-one, and (R)-2-hydroxy-3,3
      dimethoxy-1-phenyl-propan-1-one were investigated. A kinetic model optimized by
      batch experiments was developed, for the description of both batch and
      continuously operated reactors. This model was used to describe the HPP
      production in a continuously operated enzyme membrane reactor. The reactor type
      used combines the advantages of high conversion and excellent selectivity with
      high space-time yields and total turnover numbers of up to ttn=43,000. Products
      were obtained in high yield on a gram scale.

PMID- 17029296
TI  - Interaction of polyamine gene vectors with RNA leads to the dissociation of
      plasmid DNA-carrier complexes.
AB  - BACKGROUND: Plasmid DNA (pDNA) dissociation from polyamine gene vectors after
      cellular uptake has not been well characterized. A more detailed understanding of
      this process could lead to more efficient gene transfer agents. Since RNA is
      present in the cytoplasm at high concentrations and due to its structural
      similarity to DNA, we were interested in its conceivable interaction with
      polyamine gene vectors. METHODS: In a first set of experiments gene vectors were
      incubated in cell lysate and pDNA release was investigated by Southern blot
      analysis with or without RNase A pretreatment and by confocal laser scanning
      microscopy. Further, interaction of polyamine gene vectors with RNA was
      investigated by fluorescence quenching assay. These methods were complemented by
      a functionality assay using isolated nuclei. RESULTS: The incubation of gene
      vectors with cell lysate resulted in the dissociation of pDNA from the complexes.
      This effect was abolished when the cell lysate was pretreated with RNase A. The
      addition of RNA in the absence of cell lysate led also to a dissociation of pDNA.
      This process commenced instantaneously after the addition of RNA as analyzed by
      fluorescence quenching. When gene vectors were incubated in cell lysate
      containing isolated nuclei, the dissociation of pDNA from the polyamine gene
      vectors occurred preferentially extranuclearally as confirmed by confocal laser
      scanning microscopy. These results were further corroborated in a functional
      assay. CONCLUSIONS: These data suggest that RNA induces pDNA dissociation from
      the polyamine gene vectors. Furthermore, this process apparently occurs in the
      cytoplasm before the gene vectors enter the nucleus.

PMID- 17029297
TI  - Novel mutations in prenatal diagnosis of primary microcephaly.

PMID- 17029298
TI  - CT ratios: parameter estimates are inconsistent with SURUSS publications?

PMID- 17029299
TI  - Second-trimester intra-abdominal bowel dilation in fetuses with gastroschisis
      predicts neonatal bowel atresia.
AB  - OBJECTIVE: To determine in fetuses with gastroschisis the association between
      intra-abdominal bowel dilation in the second trimester and neonatal bowel
      atresia. METHODS: We reviewed ultrasound and medical records of fetuses with
      gastroschisis from January 1998 to August 2004. Fetuses with intra-abdominal
      bowel dilation in the second trimester were identified and followed into the
      neonatal period. RESULTS: We identified 58 mother-infant pairs showing fetal
      gastroschisis, with at least one prenatal ultrasound at our hospital and which
      were delivered there, or were transported there as newborns. Forty-eight of the
      58 fetuses had no intra-abdominal bowel dilation and none of these neonates had
      bowel atresia. Ten of the 58 fetuses had intra-abdominal bowel dilation and all
      had bowel atresia at birth (P<0.0001). In eight cases in which ultrasound was
      performed at <25 weeks' gestation, intra-abdominal bowel dilation was already
      present. CONCLUSION: Intra-abdominal bowel dilation in the second trimester
      predicts neonatal bowel atresia in fetuses with gastroschisis.

PMID- 17029300
TI  - Prenatal diagnosis of X chromosome monosomy.

PMID- 17029302
TI  - Commercial kit-based diagnosis is not enough for prenatal testing of beta
      thalassemia: pitfalls in diagnostic mutation analysis raises the need for
      reference laboratories.

PMID- 17029303
TI  - Effect of antipsychotic replacement with quetiapine on the symptoms and quality
      of life of schizophrenic patients with extrapyramidal symptoms.
AB  - Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a
      naturalistic setting in chronic schizophrenic patients who still showed moderate
      psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti
      parkinson drugs for the EPS. QTP was added on and gradually increased while the
      previous drugs were tapered and discontinued whenever possible. Clinical
      symptoms, objective and subjective QOL, and EPS were measured before and 6 months
      after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life
      Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced
      Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients
      completed the trial and received the assessment. It was found that replacement
      with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This
      improvement was equally observed in not only patients who switched to QTP
      monotherapy (n = 11) but also patients who took QTP together with reduced small
      doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that
      replacement with QTP improves symptoms as well as objective and subjective QOL in
      a subgroup of schizophrenia.

PMID- 17029304
TI  - Is the loudness dependence of auditory evoked potentials modulated by the
      selective serotonin reuptake inhibitor citalopram in healthy subjects?
AB  - The loudness dependence of auditory evoked potentials (LDAEP) has been discussed
      as a non-invasive in vivo marker of central serotonergic function. Evidence for
      this has been found in animal studies, but studies in humans provide less
      consistent results. In this study, the relationship between LDAEP and directly
      modulated central serotonergic activity in healthy subjects was investigated. In
      a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/-
      2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram
      diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo.
      LDAEP was measured at five different time points before, during and up to 60 min
      after drug/placebo administration and dipole source analysis was performed. The
      increase of the central serotonin activity in response to citalopram was not
      accompanied by a significant change of the LDAEP compared to the placebo
      condition. The result underlines that the acceptance of LDAEP as a marker of
      central serotonergic function still needs further discussion.

PMID- 17029305
TI  - Effect of risperidone on plasma catecholamine metabolites and brain-derived
      neurotrophic factor in patients with bipolar disorders.
AB  - A combination treatment with a mood stabilizer and an antipsychotic drug is often
      used in as many as 90% of subjects with acute mania. Recently, augmentation
      therapy with atypical antipsychotics has been investigated in both the acute and
      long-term treatment of bipolar disorder with or without psychosis. In the present
      study, the authors investigated the efficacy of risperidone treatment for both
      acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F:
      8/10, age: 34 +/- 15 yr) who met the DSM-IV criteria for bipolar I disorder (12
      cases of manic episodes, 6 cases of depressive episodes) with risperidone
      treatment were evaluated regarding their clinical improvement using the Young
      Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D).
      Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain
      derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The
      mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2,
      3, and 4 weeks after the risperidone administration, respectively. The mean
      scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2,
      3, and 4 weeks after the risperidone administration, respectively. The plasma
      levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have
      decreased 4 weeks after risperidone administration in manic patients. The levels
      did not change in depressive patients. The plasma levels of BDNF were decreased
      in depressive patients compared with manic patients or healthy controls. However,
      the administration of risperidone did not alter plasma BDNF levels.

PMID- 17029306
TI  - A case series of patients with Tourette's syndrome in the United Kingdom treated
      with aripiprazole.
AB  - OBJECTIVE: These cases illustrate that a new neuroleptic, aripiprazole, may be an
      effective treatment for the motor and vocal tics of Tourette Syndrome (TS), even
      in younger people. METHOD: A case series of 11 consecutive patients with TS (age
      range 7-50 years; M = 7) who were felt to require neuroleptic medication, were
      treated with aripiprazole, the majority of whom had been refractory to treatment
      with other neuroleptics, and in one case, Habit Reversal Training as well.
      RESULTS: Ten out of the 11 patients who were treated with aripiprazole improved,
      although to differing degrees. The only individual who showed no response was
      treated for only 1 month with a low dose (5 mg). Eight of the patients had been
      treated with many typical and atypical neuroleptics without success, and which
      had also given unacceptable side effects, resulting in them being unable to
      function at times. One was also unresponsive to previous Habit Reversal Training.
      The response to aripiprazole was dramatic and quick in five patients; in the rest
      (5/10) the response was less dramatic. In the majority of patients, response was
      sustained. The successful aripiprazole doses were between 10-20 mg daily. Side
      effects were mild and transient. This, to the best of our knowledge, is the first
      case series of patients with TS successfully treated with aripiprazole in the
      United Kingdom, and one of the few to date in the English Scientific literature.
      Our patients are also the first cases reported, in which the patients were
      assessed and whose improvement was monitored using standardised schedules and
      rating scales, such as the Yale Global Tic Severity Rating Scale and MOVES.
      Aripiprazole was licensed for use in patients with schizophrenia in the European
      Union in June 2004. We discuss possible reasons for these dramatic and
      idiosyncratic responses to aripiprazole. CONCLUSION: We suggest that aripiprazole
      may well be useful for individuals with TS as response to it is often quick,
      dramatic, sustained and with few generally mild and transient side effects.

PMID- 17029308
TI  - Fetal middle cerebral to uterine artery pulsatility index ratios in normal and
      pre-eclamptic pregnancies.
AB  - OBJECTIVES: To calculate the normal range for the fetal middle cerebral artery
      (MCA)/uterine artery pulsatility index (PI) ratio in the third trimester of
      pregnancy and to assess its value, compared with that of the MCA/umbilical artery
      PI ratio, in predicting an unfavorable outcome of pregnancies complicated by pre
      eclampsia. METHODS: Doppler blood flow velocimetry of the uterine and umbilical
      arteries and fetal MCA was performed. We calculated the ratios between 1) the PI
      of the MCA and the mean PI value of both uterine arteries and 2) the PI of the
      MCA and the PI of the umbilical artery. All women were examined at or beyond 26
      weeks of gestation. A cross-sectional study of 231 normal pregnancies was
      conducted to construct the reference range. Values below the 5th percentile or an
      MCA/umbilical artery PI ratio lower than 1.08 were defined as brain-sparing. A
      further 115 pregnancies with pre-eclampsia (50 mild and 65 severe) were assessed
      prospectively and the results were related to perinatal outcome. The accuracy of
      MCA/uterine artery and MCA/umbilical artery PI ratios for prediction of
      unfavorable pregnancy outcome was compared. RESULTS: Normal MCA/uterine artery PI
      ratios decreased with advancing gestational age. Redistribution of the fetal
      circulation indicated by a low MCA/uterine artery PI ratio was seen in 30% of the
      mild (n=15) and 46% of the severe (n=30) pre-eclamptic cases. There was a
      significant difference between those without and those with signs of brain
      sparing, respectively, in mean birth weight (2456.0 vs. 1424.5 g), gestational
      age at delivery (35.6 vs. 31.3 weeks) and gestational age at the time of
      examination (34.9 vs. 30.9 weeks). Furthermore, there was a significantly higher
      rate of small-for-gestational-age (SGA) neonates (57.8% vs. 25.7%), preterm
      delivery (100% vs. 81.8%) and Cesarean section (90.7% vs. 66.7%) in cases with an
      MCA/uterine artery PI ratio below the 5th percentile. However, there was no
      difference between the groups in the rate of low 5-min Apgar scores, admission to
      the neonatal intensive care unit, or deliveries before 34 weeks. The MCA/uterine
      artery and MCA/umbilical artery PI ratios were similar in the prediction of
      adverse perinatal outcome. Both ratios were better at predicting the outcome of
      pregnancy than were signs of increased vascular impedance in either the umbilical
      or uterine arteries. CONCLUSIONS: Normal MCA/uterine artery PI ratio decreases
      with gestational age. Abnormally low MCA/ uterine artery PI ratios are related to
      unfavorable pregnancy outcome. The predictive value of the MCA/uterine artery PI
      ratio is similar to that of the MCA/umbilical artery PI ratio.

PMID- 17029307
TI  - Verbal memory performance during subchronic challenge with a selective
      serotonergic and a mixed action antidepressant.
AB  - OBJECTIVES: Effects of escitalopram 10-20 mg/day and mirtazapine 30-45 mg/day on
      verbal memory of 18 healthy participants were assessed in a randomized, double
      blind, placebo-controlled, three-way crossover trial. METHOD: Each treatment
      period lasted for 15 days and was separated from the next period by a washout
      period of at least 13 days. Participants received an evening dose of escitalopram
      10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of
      escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2,
      9, and 16 a visual verbal memory task was performed measuring drug effects during
      the acute phase, after dose increase and at steady state. RESULTS: Escitalopram
      did not affect immediate or delayed verbal memory score throughout treatment.
      During mirtazapine treatment, participants performed less well in the overall
      immediate recall score compared to placebo. This impairment was most pronounced
      in the final trial of the visual verbal learning task. CONCLUSION: Verbal memory
      was not affected by acute and subchronic escitalopram treatment in healthy
      participants. Overall immediate verbal memory was slightly but significantly
      impaired throughout mirtazapine treatment, probably due to a general reduction in
      overall arousal caused by H1 blockade.

PMID- 17029309
TI  - Increased enantioselectivity and remarkable acceleration of lipase-catalyzed
      transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid.
AB  - Several types of imidazolium salt ionic liquids were prepared derived from
      poly(oxyethylene)alkyl sulfate and used as an additive or coating material for
      lipase-catalyzed transesterification in an organic solvent. A remarkably
      increased enantioselectivity was obtained when the salt was added at 3-10 mol %
      versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed
      transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl
      ether or a hexane solvent system. In particular, a remarkable acceleration was
      accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent
      system while maintaining excellent enantioselectivity; it reached approximately
      500- to 1000-fold acceleration for some substrates with excellent
      enantioselectivity. A similar acceleration was also observed for IL 1-coated
      Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic
      liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.

PMID- 17029310
TI  - A manganese(III) complex that exhibits spin crossover triggered by geometric
      tuning.

PMID- 17029311
TI  - Activity-stability parameterization of homogeneous green oxidation catalysts.
AB  - Small-molecule synthetic homogeneous-oxidation catalysts are normally poorly
      protected from self-destruction under operating conditions. Achieving design
      control over both activity and half-life is important not only in advancing the
      utility of oxidation catalysts, but also in minimizing hazards associated with
      their use and disposal. Iron(III)-TAML (tetraamido-macrocyclic ligand) oxidant
      catalysts rapidly activate H(2)O(2) for numerous significant processes,
      exhibiting high and differing activity and varying half-lives depending upon the
      TAML design. A general approach is presented that allows for the simultaneous
      determination of the second-order rate constant for the oxidation of a targeted
      substrate by the active catalyst (k(II)) and the rate constant for the
      intramolecular self-inactivation of the active catalyst (k(i)). The approach is
      valid if the formation of the active catalyst from its resting state and the
      primary oxidizing agent, measured by the second-order rate constant k(I), is fast
      and the catalyst concentration is very low, such that bimolecular inactivation
      pathways can be neglected. If the oxidation process is monitored
      spectrophotometrically and is set up to be incomplete, the kinetic trace can be
      analyzed by using the equation ln(lnA(t))/A(infnity)=ln(k(II)/k(i)[Fe(III)](tot)
      k(i)t, from which k(II) and k(i) can be determined. Here, A(t) and A(infinity)
      are absorbances at time t and at the end of reaction (t=infinity), respectively,
      and [Fe(III)](tot) is the total catalyst concentration. Several tools were
      applied to examine the validity of the approach by using a variety of different
      Fe(III)-TAML catalysts, H(2)O(2) and tBuOOH as oxidizing agents, and the dyes
      safranine O and orange II as target substrates. Learning how catalyst activities
      (k(II)) and catalyst half-lives (k(i)) can be controlled by ligand design is an
      important step in creating green catalysts that will not persist in the
      environment after they have achieved their purpose.

PMID- 17029312
TI  - Memory effect of activated Mg-Al hydrotalcite: in situ XRD studies during
      decomposition and gas-phase reconstruction.
AB  - The thermal decomposition of Mg-Al hydrotalcite and the subsequent reconstruction
      of the decomposed products in the presence of water vapor (2 vol. % H(2)O in
      N(2)) have been investigated by in situ XRD. Thermographic analysis and
      temperature-programmed desorption MS results complemented the diffraction data.
      Valuable mechanistic and kinetic insights into these processes, which are of
      prime importance for optimal activation of this type of material for catalytic
      applications, were obtained. Hydrotalcite decomposition to the mixed oxide
      proceeds via formation at 423-473 K of an intermediate phase, consisting of a
      highly disordered, dehydrated, layered structure. The latter evolves by removal
      of interlayer water on heating, causing a shrinking of the interlayer space (it
      is up to 45 % smaller than in the as-synthesized hydrotalcite). Above 623 K,
      Mg(Al)O(x) oxide with the periclase structure is formed. Reversion of the
      intermediate dehydrated structure to hydrotalcite upon contact with water vapor
      is complete and very fast at room temperature. Recovery of hydrotalcite from the
      oxide calcined at 723 K is two orders of magnitude slower than rehydration of the
      intermediate layered structure and one order of magnitude slower than the
      typically practiced liquid-phase reconstruction. In contrast to the
      decomposition, the reconstruction mechanism does not involve an intermediate
      phase. The gas-phase rehydration and reconstruction was interrupted above 303 K.
      This is attributed to the poor wetting of the surface of the decomposed materials
      induced by hampered H(2)O adsorption above room temperature at the water vapor
      pressure applied. The Avrami-Erofe'ev model describes the reconstruction kinetics
      well.

PMID- 17029313
TI  - O-O bond formation in the S(4) state of the oxygen-evolving complex in
      photosystem II.
AB  - Based on recent X-ray structures of the oxygen-evolving complex in photosystem
      II, quantum chemical geometry optimizations of several thousand structures have
      been performed in order to elucidate the mechanism for dioxygen formation. Many
      of the results of these calculations have been presented previously. The
      energetically most stable structure of the S(4) state has been used in the
      present study to investigate essentially all the possible ways the O--O bond can
      be formed in this structure. A key feature, emphasized previously, of the S(4)
      state is that an oxygen radical ligand is present rather than an Mn(V) state.
      Previous studies have indicated that this oxygen radical can form an O--O bond by
      an attack from a water molecule in the second coordination shell. The present
      systematic investigation has led to a new type of mechanism that is significantly
      favored over the previous one. A calculated transition-state barrier of 12.5 kcal
      mol(-1) was found for this mechanism, whereas the best previous results gave 18
      20 kcal mol(-1). A requirement on the spin alignment for a low barrier is
      formulated.

PMID- 17029314
TI  - Bridging rotaxanes' wheels--cyclochiral bonnanes.

PMID- 17029315
TI  - Tsuji-trost allylic alkylation with ketone enolates.

PMID- 17029316
TI  - On the species involved in the vaporization of imidazolium ionic liquids in a
      steam-distillation-like process.

PMID- 17029318
TI  - Highly luminescent ZnO nanocrystals stabilized by ionic-liquid components.

PMID- 17029317
TI  - Aqueous-phase hydroformylation of 1-octene: styrene latices as phase-transfer
      agents.

PMID- 17029319
TI  - Optical sensors based on nanostructured cage materials for the detection of toxic
      metal ions.

PMID- 17029320
TI  - Noncrystalline metal-boron nanotubes: synthesis, characterization, and catalytic
      hydrogenation properties.

PMID- 17029321
TI  - Halogen-bridged PtII/PtIV mixed-valence ladder compounds.

PMID- 17029322
TI  - Chiral neutral zirconium amidate complexes for the asymmetric hydroamination of
      alkenes.

PMID- 17029323
TI  - An FeVI nitride: there is plenty of room at the top!

PMID- 17029324
TI  - Ion-induced biomolecular radiation damage: from isolated nucleobases to
      nucleobase clusters.
AB  - A large number of studies are devoted to the investigation of the biomolecular
      ionization and fragmentation dynamics underlying biological radiation damage.
      Most of these studies have been based on gas-phase collisions with isolated DNA
      building blocks. The radiobiological significance of these studies is often
      questioned because of the lack of a chemical environment. To clarify this aspect,
      we studied interactions of keV ions with isolated nucleobases and with nucleobase
      clusters by means of coincidence time-of-flight spectrometry. Significant changes
      already show up in the molecular fragmentation patterns of very small clusters.

PMID- 17029325
TI  - Identification of the D(3h) isomer of carbon trioxide (CO3) and its implications
      for atmospheric chemistry.
AB  - The CO3 molecule is considered an important reaction intermediate in the
      atmospheres of Earth and Mars for quenching electronically excited oxygen atoms
      and in contributing to the anomalous 18O isotope enrichment. The geometry of the
      CO3 intermediate plays an important role in explaining these effects; however,
      only the cyclic (C(2v)) isomer has been experimentally confirmed so far. Here, we
      report on the first spectroscopic detection of the acyclic (D(3h)) isomer of
      carbon trioxide (12C16O3) via its nu1 and nu2 vibrational modes centered around
      1165 cm(-1) under matrix isolation conditions; the identification of the 12C18O3,
      13C16O3, 13C18O3, 16O12C18O2, and 18O12C16O2 isotopomers of the acyclic isomer
      confirms the assignments.

PMID- 17029327
TI  - Notice of Retraction: "Autonomous histopathological regression of primary tumours
      associated with specific immune responses to cancer antigens" (J Pathol 2003;
      200: 383-395).

PMID- 17029326
TI  - Redox-controlled photosensitization of nanocrystalline titanium dioxide.
AB  - Photosensitization of nanocrystalline titanium dioxide materials has been
      achieved by chemisorption of the pentacyanothiamineferrate(II) complex, which
      offers a relatively high redox potential that determines the photoelectrochemical
      properties of the photosensitized TiO(2). The adsorbed pentacyanoferrate complex
      binds to TiO(2) through the cyanide bridge and forms a new surface complex
      characterized by a metal-to-metal charge-transfer transition (MMCT) (Fe(II)-
      >Ti(IV)). The photosensitization can be observed only at low potentials at which
      Fe(II) moieties are present. Photocurrent switching between anodic and cathodic
      can be induced by varying either the photoelectrode potential or the wavelength
      of the incident light. Simple molecular modeling-together with spectroscopic and
      electrochemical measurements-allows the elucidation of the mechanism of the
      observed photoelectrochemical behavior.

PMID- 17029328
TI  - Contrast-enhanced cardiac computed tomographic angiography in the diagnosis of
      coronary artery stenosis or for evaluation of acute chest pain.

PMID- 17029329
TI  - Special report: fecal DNA analysis for colon cancer screening.

PMID- 17029330
TI  - Vagus nerve stimulation for treatment-resistance depression.

PMID- 17029331
TI  - Posthumous paternity testing: a proposal to amend EPTL 4-1.2(a)(2)(D).

PMID- 17029332
TI  - The interaction of law and psychiatry: a voyage over the ages.

PMID- 17029333
TI  - Can angiographic vasospasm be used as a surrogate marker in evaluating
      therapeutic interventions for cerebral vasospasm?
AB  - The authors tested the null hypothesis that published literature with a high
      level of evidence does not support the assertion that subarachnoid hemorrhage
      (SAH) causes cerebral vasospasm, which in turn causes cerebral infarction and
      poor outcome after aneurysmal SAH. The medical literature on SAH was searched in
      MEDLINE. The author's personal files of all published literature on SAH were
      reviewed. References cited in Cochrane reviews as well as the published papers
      that were reviewed were also retrieved. There is no question that SAH causes what
      the authors have chosen to call "angiographic vasospasm." However, the incidence
      and severity of vasospasm in recent series of patients is not well defined. There
      is reasonable evidence that vasospasm causes infarction, but again, accurate data
      on how severe and how diffuse vasospasm has to be to cause infarction and how
      often vasospasm is the primary cause of infarction are not available. There are
      good data on the incidence of cerebral infarction after SAH, and these data
      indicate that it is highly associated with poor outcome. The link between
      angiographic vasospasm and poor outcome is particularly poorly described in terms
      of what would be considered data of a high level of evidence. The question as to
      whether there is a clear pathway from SAH to vasospasm to cerebral infarction to
      poor outcome seems so obvious to neurosurgeons as to make it one not worth
      asking. Nevertheless, the obvious is not always true or accurate, so it is
      important to note that published literature only weakly supports the causative
      association of vasospasm with infarction and poor outcome after SAH. It behooves
      neurosurgeons to document this seemingly straightforward pathway with high
      quality evidence acceptable to the proponents of evidence-based medicine.

PMID- 17029334
TI  - Effects of acute treatment with statins on cerebral autoregulation in patients
      after aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: The authors previously have demonstrated that acute treatment with
      pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate
      vasospasm-related delayed ischemic neurological deficits (DINDs). In the current
      study, they test the hypothesis that these effects are associated with
      improvement in indices describing autoregulation of cerebral blood flow. METHODS:
      In this double-blind study, 80 patients between the ages of 18 and 84 years who
      had aneurysmal SAH were randomized equally to receive either 40 mg of oral
      pravastatin or placebo once daily for up to 14 days (medication was started 1.8 x
      1.3 days after ictus). Autoregulation was measured using a daily transient
      hyperemic response test (THRT) on transcranial Doppler ultrasonography (800
      measurements in 80 patients), and data were compared between the pravastatin and
      placebo groups and between patients with or without vasospasm, DINDs, or
      unfavorable outcome. Measurement of autoregulation also was performed using the
      pressure-reactivity index, a moving correlation coefficient between mean arterial
      and intracranial pressures (Days 0-5, 132 measurements in 32 patients). There was
      no difference in baseline autoregulation indices between the trial groups. The
      members of the pravastatin group not only had a shorter duration of impaired
      autoregulation but also had stronger transient hyperemic response ratios (THRRs)
      bilaterally. A negative correlation existed between the mean flow velocity in the
      middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral
      autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index
      correlated significantly with ipsilateral impaired autoregulation. CONCLUSIONS:
      The neuroprotective effects of acute treatment with pravastatin following
      aneurysmal SAH are associated with enhancement of autoregulation. A routine and
      daily assessment of cerebral autoregulation by using the THRT may help identify
      patients at high risk of DINDs.

PMID- 17029335
TI  - Effect of combined simvastatin and cyclosporine compared with simvastatin alone
      on cerebral vasospasm after subarachnoid hemorrhage in a canine model.
AB  - OBJECT: The object of this study was to determine whether the combination of
      cyclosporine and simvastatin could ameliorate cerebral vasospasm after
      subarachnoid hemorrhage (SAH) in a canine model to a greater extent than
      simvastatin alone. METHODS: Animals were assigned to one of three groups: control
      (five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A
      double SAH model was used. Baseline basilar artery (BA) angiograms were obtained.
      These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was
      performed. Decreased BA diameter was seen on Day 3 in the control and
      simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7.
      An increase from baseline diameter was seen in the simvastatin group at Day 10.
      CONCLUSIONS: Cyclosporine may interfere with the vasodilatory effects of
      simvastatin. Vasodilation greater than baseline is seen at Day 10 in the
      simvastatin group. The combination of simvastatin and cyclosporine does not
      ameliorate cerebral vasospasm in a canine model to a greater extent than
      simvastatin alone.

PMID- 17029336
TI  - Update on endovascular therapies for cerebral vasospasm induced by aneurysmal
      subarachnoid hemorrhage.
AB  - Cerebral vasospasm remains a major source of morbidity and death in patients with
      aneurysmal subarachnoid hemorrhage (SAH). When vasospasm becomes refractory to
      maximal medical management consisting of induced hypertension and hypervolemia
      and administration of calcium channel antagonists, endovascular therapies should
      be considered. The primary goal of endovascular treatment is to increase cerebral
      blood flow to prevent cerebral infarction. Two of the more frequently studied
      endovascular treatments are transluminal balloon angioplasty and intraarterial
      papaverine infusion. These two have been used either alone or in combination for
      the treatment of vasospasm. Other pharmacological vasodilating agents currently
      being investigated are intraarterial nimodipine, nicardipine, verapamil, and
      milrinone. Newer intraarterial agents, such as fasudil and colforsin daropate,
      have also been investigated. In this article the authors review the current
      options in terms of endovascular therapies for treatment of cerebral vasospasm.
      The mechanism of action, technique of administration, clinical effect and
      outcomes, and complications of each modality are discussed.

PMID- 17029337
TI  - Endovascular treatment strategies for cerebral vasospasm.
AB  - Cerebral vasospasm is a significant cause of morbidity and mortality in patients
      who have sustained a subarachnoid hemorrhage from aneurysm rupture. Symptomatic
      cerebral vasospasm is also a strong predictor of poor clinical outcome and has
      thus drawn a great deal of interest from cerebrovascular surgeons. Although
      medical management is the cornerstone of treatment for this condition,
      endovascular intervention may be warranted for those in whom this treatment fails
      and in whom symptomatic vasospasm subsequently develops. The rapid advancements
      in endovascular techniques and pharmacological agents used to combat this
      pathological state continue to offer promise in broadening the available
      treatment armamentarium. In this article the authors discuss the rationale and
      basis for using the various endovascular options for the treatment of cerebral
      vasospasm, and they also discuss the limitations, complications, and efficacy of
      these treatment strategies in regard to neurological condition and outcome.

PMID- 17029338
TI  - Safety and technical efficacy of over-the-wire balloons for the treatment of
      subarachnoid hemorrhage-induced cerebral vasospasm.
AB  - OBJECT: Over the past decade, low-pressure, flow-directed balloons have been
      replaced by over-the-wire balloons in the treatment of vasospasm induced by
      subarachnoid hemorrhage (SAH). The authors assess the procedural safety and
      technical efficacy of these newer devices. METHODS: Seventy-five patients who
      underwent 85 balloon angioplasty procedures for the treatment of SAH-induced
      vasospasm were identified from a prospective quality-assurance database. Medical
      records and angiographic reports were reviewed for evidence of procedural
      complications and technical efficacy. No vessel rupture or perforation occurred,
      but thromboembolic complications were noted in four (4.7%) of the 85 procedures.
      Balloon angioplasty was frequently attempted and successfully accomplished in the
      distal internal carotid (100%), proximal middle cerebral (94%), vertebral (73%),
      and basilar (88%) arteries. Severe narrowing was present in 89 proximal anterior
      cerebral arteries. Angioplasty was attempted in 41 of these vessels and was
      successful in only 14 (34%). In 19 of the 27 unsuccessful attempts, the balloon
      could not be advanced over the wire due to severe vasospasm or unfavorable vessel
      angle. Follow-up angiography in a subset of patients demonstrated that severe
      recurrent vasospasm occurred in 15 (13%) of 116 vessels studied after
      angioplasty. CONCLUSIONS: Over-the-wire balloons involve a low risk for vessel
      rupture. The anterior cerebral artery remains difficult to access and
      successfully treat with current devices. Further improvements in balloon design,
      such as smaller inflated diameters and better tracking, are necessary. Finally,
      thromboembolic complications remain an important concern, and severe vasospasm
      may recur after balloon angioplasty.

PMID- 17029339
TI  - Effect of intraarterial verapamil on the diameter of vasospastic intracranial
      arteries in patients with cerebral vasospasm.
AB  - OBJECT: This study was conducted to determine whether there is a change in
      intracranial arterial diameters after verapamil infusion for vasospasm and, if it
      is present, to determine whether the change occurs in proximal, intermediate, or
      distal vessels. METHODS: The authors measured arterial diameters in all patients
      treated with intraarterial verapamil at their institutions between August 2003
      and September 2004. In all, 18 treatments were examined in 15 patients.
      Measurements were made before and after verapamil infusion in a blinded fashion
      with the aid of a magnification loupe at nine predetermined arterial sites on
      each angiogram. Baseline arterial measurements were made on each patient's
      initial angiogram and on the angiogram demonstrating spasm prior to endovascular
      therapy as well in 14 of the patients. Charts were retrospectively reviewed to
      determine whether the patients benefited from intraarterial verapamil. From the
      time of the initial angiogram to the time of vasospasm, there was a 21.6%
      decrease (p = 0.092) in proximal artery diameter, a 47.1% decrease (p < 0.05) in
      intermediate artery diameter, and a 12.4% decrease (p < 0.05) in distal artery
      diameter. There were no significant changes in the diameters of proximal,
      intermediate, or distal vessels after verapamil infusion (mean dose 7.4 mg, range
      2.5-10 mg). After infusion of intraarterial verapamil, the proximal vessels
      showed a 1.1% decrease in diameter, the intermediate vessels showed a 9.4%
      increase, and the distal vessels showed a 3.3% decrease. CONCLUSIONS:
      Administration of intraarterial verapamil does not cause a significant increase
      in the diameter of vasospastic vessels at the administered doses.

PMID- 17029341
TI  - Vasospasm as the sole cause of cerebral ischemia: how strong is the evidence?
AB  - The authors review literature that challenges the view that vasospasm involving
      large arteries is the exclusive cause of delayed ischemic neurological deficits
      (DINDs) following subarachnoid hemorrhage. They discuss alternative mechanisms
      and review the evidence supporting a potential role for thromboembolism. They
      conclude that vasospasm and thromboembolism play interrelated and additive roles
      in the development of DINDs, and that this interaction provides opportunities for
      novel therapeutic approaches.

PMID- 17029340
TI  - Effect of intraarterial papaverine and/or angioplasty on the cerebral veins in
      patients with vasospasm after subarachnoid hemorrhage due to ruptured
      intracranial aneurysms.
AB  - OBJECT: The goal in this study was to determine if there was a change in
      intracranial venous diameters after endovascular treatment of carotid
      distribution vasospasm caused by subarachnoid hemorrhage. METHODS: The venous
      diameters were measured in all patients who received intraarterial papaverine
      and/or balloon angioplasty for treatment of vasospasm during the study period of
      3 years. To evaluate the veins of Labbe and Trolard, the straight sinus, and the
      superior sagittal sinus (SSS), measurements were performed in a blinded manner
      with the aid of a magnification loupe. Predetermined sites were evaluated on
      angiograms obtained before and after endovascular treatment. Forty-three
      treatments in 26 patients were included: 18 patients (33 territories) were
      treated with intraarterial papaverine alone, four (four territories) were treated
      with balloon angioplasty alone, and four (six territories) were treated with both
      papaverine infusion and angioplasty. The mean measured venous diameters increased
      significantly after addition of papaverine (10.9%), and also after combined
      papaverine and angioplasty (4.2%). There was no statistically significant
      increase in the mean venous diameters after angioplasty alone. If the initial
      intracranial pressure (ICP) was less than 15 mm Hg before treatment, the veins
      showed a greater tendency to dilate than if the initial ICP measurements were
      greater than 15 mm Hg. The straight sinus and the SSS increased more in diameter
      than the veins of Labbe and Trolard. There was no statistically significant
      correlation between the change in venous diameters with treatment and ICP.
      CONCLUSIONS: Endovascular treatment produces measurable increases in intracranial
      venous diameters. However, these changes do not correlate with changes in ICP.

PMID- 17029342
TI  - Update on evidence for a genetic predisposition to cerebral vasospasm.
AB  - Considerable evidence links cerebral vasospasm to the decreased bioavailability
      of endothelial nitric oxide synthase (eNOS) after aneurysmal subarachnoid
      hemorrhage (SAH). In recent studies from the cardiology literature, researchers
      have suggested that a genetic predisposition to coronary vasospasm might develop
      as the result of a T-786C single nucleotide polymorphism (SNP) in the eNOS gene.
      The authors of this study attempted to determine if there may be a similar
      genetic predisposition toward cerebral vasospasm. The authors prospectively
      identified 28 patients with Fisher Grade 3 SAH from a group of 51 consecutive
      patients with ruptured intracranial saccular aneurysms. Genomic DNA was isolated
      from a peripheral blood sample obtained with permission from each patient. Gene
      microarray technology was used to assay the samples for the presence and
      distribution of certain key eNOS gene polymorphisms. Clinical, radiological, and
      genomic data were analyzed. The finding of eNOS T-786C SNP could be used to
      significantly differentiate between the presence and severity of cerebral
      vasospasm (p = 0.04). The findings from this preliminary study support similar
      findings in the coronary vasospasm literature as well as the hypothesis that a
      predisposition toward cerebral vasospasm may be related partially to genetic
      factors, which needs to be confirmed in a larger study. Such gene-based
      information may be important in rapidly identifying patients at increased risk of
      vasospasm after SAH, independent of their Fisher grade. In this article, the
      authors review key studies in this area.

PMID- 17029344
TI  - Computed tomography grading schemes used to predict cerebral vasospasm after
      aneurysmal subarachnoid hemorrhage: a historical review.
AB  - The elucidation of predictive factors of cerebral vasospasm following aneurysmal
      subarachnoid hemorrhage (SAH) is a major area of both clinical and basic science
      research. It is becoming clear that many factors contribute to this phenomenon.
      The most consistent predictor of vasospasm has been the amount of SAH seen on the
      postictal computed tomography scan. Over the last 30 years, it has become clear
      that the greater the amount of blood within the basal cisterns, the greater the
      risk of vasospasm. To evaluate this risk, various grading schemes have been
      proposed, from simple to elaborate, the most widely known being the Fisher scale.
      Most recently, volumetric quantification and clearance models have provided the
      most detailed analysis. Intraventricular hemorrhage, although not supported as
      strongly as cisternal SAH, has also been shown to be a risk factor for vasospasm.

PMID- 17029343
TI  - Dissociation between vasospasm and functional improvement in a murine model of
      subarachnoid hemorrhage.
AB  - OBJECT: The efficacy of nimodipine was examined in a murine model of subarachnoid
      hemorrhage (SAH). End points included the diameter of the lumen of the middle
      cerebral artery (MCA) and behavioral outcome. An apolipoprotein E (apoE)-mimetic
      peptide, acetyl-AS-Aib-LRKL-Aib-KRLL-amide, previously shown to have promise in
      this model was tested both alone and in combination with nimodipine. The effects
      of carboxyamidotriazole (CAI), a non-voltage-gated calcium channel blocker, were
      explored using the same animal paradigm. METHODS: Experimental SAH was induced in
      male C57B1/6J mice. For 3 days postoperatively, behavioral analyses were
      performed. In the first experiment, the mice were treated with vehicle or with
      low- or high-dose CAI for 3 days. In the second experiment, the mice were treated
      with vehicle, high- and low-dose nimodipine, and/or the apoE-mimetic peptide. On
      postoperative Day 3 each mouse was killed and perfused. Following this, the right
      MCA was removed and its lumen measured. Mice that received nimodipine
      demonstrated significant behavioral improvements when compared with vehicle
      treated mice, but there was no clear dose-dependent effect on MCA diameter.
      Administration of the apoE-mimetic peptide was associated with improved
      functional performance and a significant reduction in vasospasm. Mice that
      received high-dose CAI performed worse on functional tests, despite a significant
      increase in the diameters of their MCA lumina. CONCLUSIONS: These results
      demonstrate a dissociation between vasospasm and neurological outcomes that is
      consistent with findings of previous clinical trials.

PMID- 17029345
TI  - Utility of computed tomography perfusion in detection of cerebral vasospasm in
      patients with subarachnoid hemorrhage.
AB  - OBJECT: Digital subtraction (DS) angiography is the gold standard for detecting
      cerebral vasospasm after subarachnoid hemorrhage (SAH). Computed tomography (CT)
      perfusion is a recently developed modality for the evaluation of cerebral
      hemodynamics. This study was conducted to evaluate the potential of using CT
      perfusion to detect vasospasm in patients with SAH. METHODS: Fourteen patients
      between the ages of 41 and 66 years with aneurysmal SAH underwent 23 CT perfusion
      scans for suspected vasospasm. All patients underwent DS angiography within 12
      hours of the CT perfusion scans. The presence of vasospasm on CT perfusion images
      was determined based on qualitative reading using color maps of mean transit
      time, cerebral blood flow, and cerebral blood volume as criteria. The presence or
      absence of vasospasm as retrospectively determined using CT perfusion was
      compared with DS angiography findings. Of the 23 CT perfusion scans performed, 21
      (91%) were concordant with angiography findings in predicting the presence or
      absence of vasospasm. In 15 of 23 scans, the presence of vasospasm was detected
      on CT perfusion scans and confirmed on DS angiography studies. In two cases,
      vasospasm was revealed on DS angiography but was not confirmed on CT perfusion.
      The degree of agreement between CT perfusion and DS angiography for detection of
      vasospasm was high (K = 0.8, p , 0.0001). CONCLUSIONS: Computed tomography
      perfusion is an accurate, reliable, and noninvasive method to detect the presence
      or absence of vasospasm. It can be used as a tool to help guide the decision to
      pursue DS angiography with the intent to treat vasospasm.

PMID- 17029346
TI  - Cerebral perfusion imaging in vasospasm.
AB  - Vasospasm following cerebral aneurysm rupture is one of the most devastating
      sequelae and the most common cause of delayed ischemic neurological deficit
      (DIND). Because vasospasm also is the most common cause of morbidity and
      mortality in patients who survive the initial bleeding episode, it is imperative
      not only to diagnose the condition but also to predict which patients are likely
      to become symptomatic. The exact pathophysiology of vasospasm is complex and
      incompletely elucidated. Early recognition of vasospasm is essential because the
      timely use of several therapeutic interventions can counteract this disease and
      prevent the occurrence of DIND. However, the prompt implementation of these
      therapies depends on the ability to predict impending vasospasm or to diagnose it
      at its early stages. A number of techniques have been developed during the past
      several decades to evaluate cerebral perfusion, including positron emission
      tomography, xenon-enhanced computed tomography, single-photon emission computed
      tomography, perfusion- and diffusion-weighted magnetic resonance imaging, and
      perfusion computed tomography. In this article, the authors provide a general
      overview of the currently available perfusion imaging techniques and their
      applications in treating vasospasm after a patient has suffered a subarachnoid
      hemorrhage. The use of cerebral perfusion imaging techniques for the early
      detection of vasospasm is becoming more common and may provide opportunities for
      early therapeutic intervention to counteract vasospasm in its earliest stages and
      prevent the occurrence of DINDs.

PMID- 17029347
TI  - Evidence-based cerebral vasospasm management.
AB  - Cerebral vasospasm and delayed cerebral ischemia remain common complications of
      aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral
      vasospasm are limited. Despite a large number of clinical trials, only calcium
      antagonists have strong evidence supporting their effectiveness. The purpose of
      this work was to perform a systematic review of the literature on the treatment
      of cerebral vasospasm. A literature search for randomized controlled trials of
      therapies used for prevention or treatment of cerebral vasospasm and/or delayed
      cerebral ischemia was conducted, and 41 articles meeting the review criteria were
      found. Study characteristics and primary results of these articles are reviewed.
      Key indicators of quality were poor when averaged across all studies, but have
      improved greatly over time. The only proven therapy for vasospasm is nimodipine.
      Tirilazad is not effective, and studies of hemodynamic maneuvers, magnesium,
      statin medications, endothelin antagonists, steroid drugs,
      anticoagulant/antiplatelet agents, and intrathecal fibrinolytic drugs have
      yielded inconclusive results. The following conclusions were made: nimodipine is
      indicated after SAH and tirilazad is not effective. More study of hemodynamic
      maneuvers, the effectiveness of other calcium channel antagonists such as
      nicardipine delivered by other routes (for example intrathecally), magnesium,
      statin drugs, endothelin antagonists, and intrathecal fibrinolytic therapy is
      warranted. There is less enthusiasm for the study of steroid drugs and
      anticoagulant/antiplatelet agents because they entail more risks and
      investigations so far have shown little evidence of efficacy. The study of rescue
      therapy such as balloon angioplasty and intraarterial vasodilating agents will be
      difficult. The quality of clinical trials should be improved.

PMID- 17029348
TI  - A review of current and future medical therapies for cerebral vasospasm following
      aneurysmal subarachnoid hemorrhage.
AB  - In an effort to help clarify the current state of medical therapy for cerebral
      vasospasm, the authors reviewed the relevant literature on the established
      medical therapies used for cerebral vasospasm following aneurysmal subarachnoid
      hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite
      advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common
      complication and has been correlated with a 1.5- to threefold increase in death
      during the first 2 weeks after hemorrhage. A number of medical, pharmacological,
      and surgical therapies are currently in use or being investigated in an attempt
      to reverse cerebral vasospasm, but only a few have proven to be useful. Although
      much has been elucidated regarding its pathophysiology, the treatment of cerebral
      vasospasm remains a dilemma. Although a poor understanding of SAH-induced
      cerebral vasospasm pathophysiology has, to date, hampered the development of
      therapeutic interventions, current research efforts promise the eventual
      production of new medical therapies.

PMID- 17029349
TI  - Synthesis and reactivity of a new octanuclear iron-sulfur nitrosyl cluster.
AB  - The synthesis and spectroscopic properties of (PPN)2[Fe8S6(NO)8] as well as its
      reactivity toward sulfur are reported.

PMID- 17029350
TI  - A traditional synthetic method, and a new structural motif, for molybdenum-gold
      clusters: synthesis and solid-state structure of Au8{Mo(CO)5}4(PPh3)4.
AB  - The neutral cluster [Au8Mo4(CO)20(PPh3)4] was synthesized in low yield from
      [AuCl(PPh3)] and [Mo2(CO)10]2- in acetonitrile at room temperature. The cluster
      was characterized by X-ray analysis, IR, and 31P NMR spectroscopy. Its solid
      state structure consists of four Au(3)Mo tetrahedral units, fused by four Au
      atoms in a ring. The average bond lengths are Au-Au 2.77 Angstrom and Mo-Au 2.93
      Angstrom. The internal angles of the planar square ring are very close to 90
      degrees.

PMID- 17029351
TI  - New 3-D La(III)-Cu(II)-containing coordination polymer with a high potential
      porosity.
AB  - A new 3-D coordination polymer containing both 3d and 4f ions has been designed.
      Its chemical formula is La2[Cu(pba)]3(H2O)8 . 8H2O. It crystallizes in the
      quadratic system, space group I41/a with a = 42.4947(9) Angstrom, c = 16.3378(3)
      Angstrom, and Z = 16. Its crystal structure can be described as a 3-D molecular
      framework exhibiting a complex network of interconnected zigzaglike channels.
      Once crystallization water molecules are removed, this compound presents a high
      potential porosity and a low density. The porosity has been evaluated using
      Connolly's algorithm.

PMID- 17029352
TI  - First 3D 3d-4f interpenetrating structure: synthesis, reaction, and
      characterization of {[LnCr(IDA)2(C2O4)]}n.
AB  - The hydrothermal reaction of Cr(NO3)3, Ln2O3, and iminodiacetate acid (H(2)IDA)
      in the molar ratio of 1:1:3 produced {[LnCr(IDA)2(C2O4)]}n (Ln = Eu, 1; Sm, 2),
      which represent the first 3D 3d-4f interpenetrating coordination polymers. In the
      reaction, the H(2)IDA ligands partly decompose into oxalate anions (ox), which
      connect Ln(III) ions to form 1D {Ln(ox)}n chains. Each of the Cr(III) ions is
      tridentate-coordinated by two IDA ligands, which act as tetradentate
      metalloligands to link {Ln(ox)}n chains to form 3D open networks. The two open
      networks interpenetrate each other to form nonporous products. 1 and 2 are
      thermally stable up to 327 and 360 degrees C, respectively. Both of complexes
      show normally paramagnetic behavior. The luminescent results imply that the
      energy transfers from Ln(III) to Cr(III) are strong.

PMID- 17029353
TI  - Intersite structural rearrangement of the blue copper site induced by substrate
      binding: spectroscopic studies of a copper-containing nitrite reductase from
      Alcaligenes xylosoxidans NCIMB 11015.
AB  - A copper-containing nitrite reductase from Alcaligenes xylosoxidans NCIMB 11015
      has its own unique blue or type 1 copper protein resonance Raman spectrum in the
      usual Cu-S(Cys) stretching region, nu(Cu-S(Cys)), with a pair of strong peaks at
      412 and 420 cm(-1) and a weak peak at 364 cm(-1). The predominantly nu(Cu-S(Cys))
      Raman bands at 412, 420, and 364 cm(-1) of the type 1 copper site all shifted to
      higher frequencies upon binding of nitrite to the type 2 copper site, and the
      resonance Raman difference spectra progressively intensified with the increments
      of nitrite ion concentration. Positive support for substrate binding to the type
      2 copper is provided by the nu(Cu-S(Cys)) bands in the resonance Raman spectrum
      of a type 2 copper-depleted enzyme, which is insensitive to the presence of NO2-.
      The shift to higher frequency of the Raman bands of the type 1 copper center with
      the addition of nitrite ions suggests a stronger Cu-S(Cys) interaction in the
      substrate-bound A. xylosoxidans nitrite reductase.

PMID- 17029354
TI  - An isolable, nonreducible high-valent manganese(V) imido corrolazine complex.
AB  - The manganese(V) imido complex [(TBP8Cz)Mn(V)(NMes)] (2) was synthesized from the
      Mn(III) complex [(TBP8Cz)Mn(III)] (1) and thermolysis of mesityl azide. An X-ray
      structure of 2 reveals a short Mn-N distance [1.595(4) A], consistent with the Mn
      N triple bond expected for a manganese(V) imido species. This high-valent species
      is remarkably inert to one- and two-electron reductive processes such as NR group
      transfer to alkenes or H-atom abstraction from O-H bonds. Electrochemical studies
      support this lack of reactivity. In contrast, oxidation of 2 is easily
      accomplished by treatment with [(4-BrC6H4)3N]*+SbCl6, giving a pi-radical-cation
      complex.

PMID- 17029355
TI  - Nonfluorinated volatile copper(I) 1,3-diketiminates as precursors for Cu metal
      deposition via atomic layer deposition.
AB  - Novel nonfluorinated Cu(diketiminate)L complexes with L = neutral olefinic ligand
      have been prepared as stable, volatile Cu(I) precursors for the deposition of
      copper films by an atomic layer deposition (ALD) process. Among them, the
      complexes of 4-a and 5-a are the most volatile and stable at low temperature (55
      degrees C). A clean, conformal copper film was deposited at 120 degrees C in an
      ALD process. These Cu(I) complexes are the first examples of nonfluorinated
      copper(I) diketiminates that can be readily applied to an industrial
      microelectronic fabrication process.

PMID- 17029356
TI  - The structure and synthesis of plutonium(III) chlorides from aqueous solution.
AB  - The preparation and structure of three trivalent plutonium chloride compounds
      from aqueous solution is reported. Two of the three are plutonium
      tetraaquatetrachloro complexes exhibiting a cis and a trans arrangement of Cl
      about the Pu. The identification of the coordination number of 4 with respect to
      Cl and the isomerism are both unprecedented in actinide solution chemistry. The
      third complex is a hexaaquadichloro complex of Pu(III), predicted by available
      thermodynamic data.

PMID- 17029357
TI  - Luminescent 2-D double-layered polymer, [(CuI)4(CH3SCH3)3]infinity, containing
      helical chains constructed by flower-basket-shaped Cu4I4 clusters.
AB  - A new route for the synthesis of coordination compounds with dimethyl sulfide
      ligand is reported; the prepared compound is a novel 2-D framework with a 1-D
      right-handed and left-handed helical structure, which is unique in the sense that
      the fundamental units are unusual Cu4I4 clusters.

PMID- 17029358
TI  - Synthesis and characterization of a doxorubicin-Gd(III) contrast agent conjugate:
      a new approach toward prodrug-procontrast complexes.
AB  - We have prepared the first MRI prodrug-procontrast complex by conjugating
      doxorubicin to a Gd(III) chelate using an acid-labile linker. The relaxometric
      properties of the adduct and pH activation are reported.

PMID- 17029359
TI  - Ultrahigh-field NMR spectroscopy of quadrupolar transition metals: 55Mn NMR of
      several solid manganese carbonyls.
AB  - 55Mn NMR spectra acquired at 21.14 T (nu(L)(55Mn) = 223.1 MHz) are presented and
      demonstrate the advantages of using ultrahigh magnetic fields for characterizing
      the chemical shift tensors of several manganese carbonyls: eta5-CpMn(CO)3,
      Mn2(CO)10, and (CO)5MnMPh3 (M = Ge, Sn, Pb). For the compounds investigated, the
      anisotropies of the manganese chemical shift tensors are less than 250 ppm except
      for eta5-CpMn(CO)3, which has an anisotropy of 920 ppm. At 21.14 T, one can
      excite the entire m(I) = 1/2 <--> m(I) = -1/2 central transition of eta5
      CpMn(CO)3, which has a breadth of approximately 700 kHz. The breadth arises from
      second-order quadrupolar broadening due to the 55Mn quadrupolar coupling constant
      of 64.3 MHz, as well as the anisotropic shielding. Subtle variations in the
      electric field gradient tensors at the manganese are observed for
      crystallographically unique sites in two of the solid pentacarbonyls, resulting
      in measurably different C(Q) values. MQMAS experiments are able to distinguish
      four magnetically unique Mn sites in (CO)(5)MnPbPh3, each with slightly different
      values of delta(iso), C(Q), and eta(Q).

PMID- 17029360
TI  - Metal-binding thermodynamics of the histidine-rich sequence from the metal
      transport protein IRT1 of Arabidopsis thaliana.
AB  - The widespread ZIP family of transmembrane metal-transporting proteins is
      characterized by a large intracellular loop that contains a histidine-rich
      sequence whose biological role is unknown. To provide a chemical basis for this
      role, we prepared and studied a peptide corresponding to this sequence from the
      first iron-regulated transporter (IRT1) of Arabidopsis thaliana, which transports
      Fe2+ as well as Mn2+, Co2+, Zn2+, and Cd2+. Isothermal titration calorimetry
      (ITC) measurements, which required novel experiments and data analysis, and
      supporting spectroscopic methods were used to quantify IRT1's metal-binding
      affinity and associated thermodynamics. The peptide, PHGHGHGHGP, binds metal ions
      with 1:1 stoichiometry and stabilities that are consistent with the Irving
      Williams series. Comparison of the metal-binding thermodynamics of the peptide
      with those of trien provides new insight about enthalpic and entropic
      contributions to the stability of the metal-peptide complex. Although Fe2+ and
      other IRT1-transported metal ions do not bind very tightly, this His-rich
      sequence has a very high entropy-driven affinity for Fe3+, which may have
      biological significance.

PMID- 17029361
TI  - Computational comparison of cation coordination to human prion peptide models.
AB  - The coordination of the cations Cu(II), Co(II), Rh(III), Ir(III), Ni(II), Pd(II),
      Pt(II), and Zn(II) to the copper-binding octapeptide region in the human prion
      protein has been compared through structural optimization. The initial
      coordination mode used in the calculations is a five-coordinated mode obtained
      from previously published crystallographic data for Cu(II). The computational
      results show that, among these cations, the coordinations of Co(II) and Rh(III)
      are the most similar to that of Cu(II). The cations Ni(II), Pd(II), and Pt(II)
      prefer a four-coordinate square-planar coordination by the peptide ligand. The
      paramagnetic Co(II) ion with its large quadrupole moment is not a good substitute
      for Cu(II) to be used in NMR spectroscopic studies of the coordinated peptide
      region. Rh(III) has more attractive NMR spectroscopic characteristics than Cu(II)
      and Co(II) and may represent a suitable substitute for Cu(II) in these types of
      studies. Some preliminary experimental studies using NMR spectroscopic methods
      indicate that Rh(III) coordinates the copper-binding octapeptide region of the
      human prion protein, although further studies are required to determine the mode
      of interaction in detail.

PMID- 17029362
TI  - Toward a clear-cut vision on the origin of 2,6-di(1,2,4-triazin-3-yl)pyridine
      selectivity for trivalent actinides: insights from theory.
AB  - Although BTP (2,6-di(1,2,4-triazin-3-yl)pyridine) has been widely evidenced as
      the most effective nitrogen ligand for the selective complexation of trivalent
      actinides from lanthanide counterparts, the origin of its selectivity is still an
      open question. Neither experimental data nor theoretical calculations have been
      able to rationalize the role of covalency in real experimental BTP complexes. We
      show herein with DFT calculations on [M(BTP)3]3+ (M = La, U, Cm, Gd) that, even
      if back-bonding effects are significant in the U-BTP bond, it is the contrast of
      donation on 6d and 5f Cm(III) orbitals that explains, at least in part, its
      selective complexation to BTP.

PMID- 17029363
TI  - Syntheses, structures, and photoluminescence properties of metal(II) halide
      complexes with pyridine-containing flexible tripodal ligands.
AB  - Seven coordination compounds, [Zn(L3)Cl2] . MeOH . H2O (1), [Mn(L3)2Cl2] .
      0.5EtOH . 0.5H2O (2), [Cu3(L2)2Cl6] . 2DMF (3), [Cu3(L2)2Br6] . 4MeOH (4),
      [Hg2(L4)Cl4] (5), [Hg2(L4)Br4] (6), and [Hg3(L4)2I6] . H2O (7), were synthesized
      by the reactions of ligands 1,3,5-tris(3-pyridylmethoxyl)benzene (L3), 1,3,5
      tris(2-pyridylmethoxyl)benzene (L2), and 1,3,5-tris(4-pyridylmethoxyl)benzene
      (L4) with the corresponding metal halides. All the structures were established by
      single-crystal X-ray diffraction analysis. In complexes 1 and 2, L3 acts as a
      bidentate ligand using two of three pyridyl arms to link two metal atoms to
      result in two different 1D chain structures. In complexes 3 and 4, each L2 serves
      as tridentate ligand and connects three Cu(II) atoms to form a 2D network
      structure. Complexes 5 and 6 have the same framework structure, and L4 acts as a
      three-connecting ligand to connect Hg(II) atoms to generate a 3D 4-fold
      interpenetrated framework, while the structure of complex 7 is an infinite 1D
      chain. The results indicate that the flexible ligands can adopt different
      conformations and thus can form complexes with varied structures. In addition,
      the coordination geometry of the metal atom and the species of the halide were
      found to have great impact on the structure of the complexes. The
      photoluminescence properties of the complexes were investigated, and the Zn(II),
      Mn(II) and Hg(II) complexes showed blue emissions in solid state at room
      temperature.

PMID- 17029365
TI  - Necklace-like hollow carbon nanospheres from the pentagon-including reactants:
      synthesis and electrochemical properties.
AB  - Necklace-like hollow carbon nanospheres (CNSs) have been successfully synthesized
      from the pentagon-including reactants, which provide an auxiliary example for the
      theoretical prediction that necklace-like hollow CNSs are assumed to be composed
      of the regular occurrence of nonhexagonal rings at the atomic level. Benefits of
      the as-obtained hollow CNSs also arise from the high Brunauer-Emmett-Teller value
      of 594.32 m(2)/g and a narrow pore distribution at 5 nm. The electrochemical
      hydrogen storage experiments for the as-obtained necklace-like hollow CNSs
      exhibit a capacity of 242 mAh/g at the current density of 200 mA/g, corresponding
      to a hydrogen storage of 0.89 wt %, which is higher than the previously reported
      electrochemical capacities for the multiwalled carbon nanotubes (MWCNTs).
      Furthermore, the as-obtained necklace-like hollow CNSs show a lithium capacity
      advantage compared with the carbon solid particles for application in lithium
      batteries. These results indicate that the necklace-like hollow CNSs provide a
      new candidate for the application in hydrogen storage and lithium batteries.

PMID- 17029364
TI  - Density functional theory study of Fe(IV) d-d optical transitions in active-site
      models of class I ribonucleotide reductase intermediate X with vertical self
      consistent reaction field methods.
AB  - The Fe(IV) d-d transition energies for four active-site structural models of
      class I ribonucleotide reductase (RNR) intermediate X have been calculated using
      broken-symmetry density functional theory incorporated with the Slater transition
      state vertical self-consistent reaction field methodology. Our model I (Figure
      1), which contains two mu-oxo bridges, one terminal water, and one bidentate
      carboxylate group, yields the best Fe(IV) d-d transition energies compared with
      experiment. Our previous study (J. Am. Chem. Soc. 2005, 127, 15778-15790) also
      shows that most of the other calculated properties of model I in both native and
      mutant Y122F forms, including geometries, spin states, pKa's, 57Fe, 1H, and 17O
      hyperfine tensors, and 57Fe Mossbauer isomer shifts and quadrupole splittings,
      are also the best in agreement with the available experimental data. This model
      is likely to represent the active-site structure of the intermediate state X of
      RNR.

PMID- 17029366
TI  - Isomeric distribution and catalyzed isomerization of cobalt(III) complexes with
      pentadentate macrocyclic ligands. importance of hydrogen bonding.
AB  - We have investigated the isomeric distribution and rearrangement of complexes of
      the type [CoXLn]2+,3+ (where X = Cl-, OH-, H2O, and Ln represents a pentadentate
      13-, 14-, and 15-membered tetra-aza or diaza-dithia (N4 or N2S2) macrocycle
      bearing a pendant primary amine). The preparative procedures for chloro complexes
      produced almost exclusively kinetically preferred cis isomers (where the pendant
      primary amine is cis to the chloro ligand) that can be separated by careful
      cation-exchange chromatography. For L13 and L14 the so-called cis-V isomer is
      isolated as the kinetic product, and for L15 the cis-VI form (an N-based
      diastereomer) is the preferred, while for the L14(S) complex both cis-V and trans
      I forms are obtained. All these complexes rearrange to form stable trans isomers
      in which the pendent primary amine is trans to the monodentate aqua or hydroxo
      ligand, depending on pH and the workup procedure. In total 11 different complexes
      have been studied. From these, two different trans isomers of [CoClL14(S)]2+ have
      been characterized crystallographically for the first time in addition to a new
      structure of cis-V-[CoClL14(S)]2+; all were isolated as their chloride
      perchlorate salts. Two additional isomers have been identified and characterized
      by NMR as reaction intermediates. The remaining seven forms correspond to the
      complexes already known, produced in preparative procedures. The kinetic,
      thermal, and baric activation parameters for all the isomerization reactions have
      been determined and involve large activation enthalpies and positive volumes of
      activation. Activation entropies indicate a very important degree of hydrogen
      bonding in the reactivity of the complexes, confirmed by density functional
      theory studies on the stability of the different isomeric forms. The
      isomerization processes are not simple and even some unstable intermediates have
      been detected and characterized as part of the above-mentioned 11 forms of the
      complexes. A common reaction mechanism for the isomerization reactions has been
      proposed for all the complexes derived from the observed kinetic and solution
      behavior.

PMID- 17029367
TI  - Investigation of the pronounced medium effects observed in the voltammetry of the
      highly charged lacunary anions [alpha-SiW11O39]8- and [alpha-PW11O39]7-.
AB  - A detailed study is reported of the influence of protons, metal cations, and
      media on the redox chemistry of lacunary anions [alpha-SiW11O39]8- and [alpha
      PW11O39]7- of high formal negative charge. Each anion displayed a single
      chemically reversible one-electron reduction process in carefully dried aprotic
      CH3CN solution. This process was detected at very negative potentials just prior
      to the solvent limit. Addition of 0.3 equiv of acid gave rise to a new reduction
      process at considerably less negative potentials, which is attributed to
      formation of the protonated species [SiW11O38(OH)]7- and [PW11O38(OH)]6-.
      Voltammograms derived from simulations based on a double-square scheme are in
      excellent agreement with experiment. Previous data reported the presence of
      several processes in CH3CN and appear to have been influenced by the presence of
      protons and/or adventitious water. Not surprisingly, protonation reactions
      coupled to charge transfer contribute significantly to the voltammetry of these
      lacunary anions in buffered aqueous media over the pH range 2-6. A multi-square
      scheme mechanism allowed the essential thermodynamic and kinetic features of this
      system to be captured and an assessment of the relative significance of possible
      individual pathways. The high formal anionic charges of [SiW11O39]8- and
      [PW11O39]7- appear to provide highly basic reduced forms that are able to
      abstract protons from water to produce protonated species which are reduced at
      potentials more than a volt less negative than those for the processes
      [SiW11O39]8-/9- and [PW11O39]7-/8- found in dry aprotic media.

PMID- 17029368
TI  - Dilacunary decatungstates functionalized by organometallic ruthenium(II),
      [{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-XW10O36)]4- (X = Si, Ge).
AB  - The benzene-Ru(II)-supported dilacunary decatungstosilicate
      [{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-SiW10O36)]4- and the isostructural
      decatungstogermanate [{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-GeW10O36)]4- have been
      synthesized and characterized by multinuclear solution NMR, IR, elemental
      analysis, and electrochemistry. Single-crystal X-ray analysis was carried out on
      K4[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-SiW10O36)].9H2O (K-1), which crystallizes in
      the orthorhombic system, space group Pmn2(1), with a = 13.6702(3) A, b =
      16.2419(4) A, c = 12.1397(2) A, and Z = 2, and on
      K4[{Ru(C6H6)(H2O)}{Ru(C6H6)}(gamma-GeW10O36)].7H2O (K-2), which also crystallizes
      in the orthorhombic system, space group Pmn2(1), with a = 13.6684(12) A, b =
      16.297(2) A, c = 12.1607(13) A, and Z = 2. Polyanions 1 and 2 consist of a
      Ru(C6H6)(H2O) group and a Ru(C6H6) group linked to a dilacunary (gamma-XW10O36)
      Keggin fragment resulting in an assembly with idealized Cs symmetry. The
      Ru(C6H6)(H2O) group is bound at the lacunary polyanion site via two Ru-O(W)
      bonds, whereas the Ru(C6H6) group is bound on the side via three Ru-O(W) bonds.
      Polyanions 1 and 2 were synthesized in aqueous acidic medium at pH 2.5 by the
      reaction of [Ru(C6H6)Cl2]2 with [gamma-SiW10O36]8- and [gamma-GeW10O36]8-,
      respectively. The formal potentials are roughly the same for the first W waves of
      1 and 2. However, important differences appear for the second W waves. These
      observations indicate different acid-base properties for the reduced forms of 1
      and 2. Three oxidation processes were detected: the oxidation of the Ru center is
      followed first by irreversible electrocatalytic processes of the Ru-benzene
      moiety and then of the electrolyte. Comparison of this behavior with that of the
      precursor reagent, [Ru(C6H6)Cl2]2, was useful to understand the main oxidation
      processes. A ligand substitution reaction was observed upon addition of dimethyl
      sulfoxide (dmso) to 1, 2, or [Ru(C6H6)Cl2]2. This reaction facilitates
      substantially the oxidation of the Ru center. The dmso was oxidized with large
      electrocatalytic currents more efficiently in the presence of 1 and 2 than with
      [Ru(C6H6)Cl2]2.

PMID- 17029369
TI  - Synthesis, structure, and photophysical properties of luminescent platinum(II)
      complexes containing cyclometalated 4-styryl-functionalized 2-phenylpyridine
      ligands.
AB  - A series of new luminescent cyclometalated platinum(II) complexes functionalized
      with various substituted styryl groups on the cyclometallating ligand [Pt(C/?N
      ppy-4-styryl-R)(O/?O-(O)CCR'CHCR'C(O))] (ppy-4-styryl-R = E-4(4-(R)styryl-2
      phenylpyridine) (3, R' = Me (acac); 4, R' = (t)Bu (dpm); R = H, OMe, NEt2, NO2)
      have been prepared. All complexes undergo an E-Z photoisomerization process in
      CH2Cl2 solution under sunlight, as monitored by 1H NMR. The solid-state
      structures of 3-OMe, 3-NEt2, 3-NO2, and 4-OMe have been determined by X-ray
      diffraction studies and compare well with optimized geometries obtained by
      density functional theory (DFT) calculations. The orbital pictures of 3-H, 3-OMe,
      and 3-NO 2 are very similar, the highest occupied molecular orbital (HOMO) being
      highly Pt(5d) metal-based. For 3-NMe2, an additional contribution from the amino
      styryl fragment leads to a decreased metal parentage of the HOMO, suggesting a
      predominantly ILCT character transition. Complexes 3-H, 3-OMe, and 3-NO2 show a
      low-energy band (350-400 nm) assigned to predominantly charge-transfer
      transitions. The amino derivative 3-NEt2 displays a very strong absorption band
      at 432 nm, tentatively assigned to a mixture of ILCT (Et2N --> CH=CH) and metal
      to-ligand charge-transfer (MLCT) (dpi(Pt) --> pi) transitions. Complexes 3 are
      weakly luminescent in CH2Cl2 solution at room temperature; the low intensity may
      be due to a competitive quenching through the E-Z photoisomerization process. All
      complexes exhibit similar structured emission bands under these conditions
      (around 520 nm), independent of the nature of the styryl-R group. In a frozen EPA
      glass (77 K), the spectrum of the representative complex 3-H exhibits two sets of
      vibronically structured bands (460-560, 570-800 nm; lambda(max) = 596 nm), due to
      the presence of two emitting species, the E and Z isomers, which have
      significantly different triplet excited-state energies. The other three complexes
      show similar behavior to 3-H at 77 K, but the lower-energy emission bands are
      progressively red-shifted in the order H < OMe < NO2 < NEt2 (e.g., for 3-NEt2,
      lambda(max)(em) = 658 nm; tau = 26 micros). The very large red-shift compared to
      related unsubstituted complexes (e.g., to [Pt(C/?N-ppy)(O/?O-acac)]) is the
      result of the extension of the pi-conjugated system and the electronic effects of
      substituent R.

PMID- 17029371
TI  - New ruthenium nitrosyl complexes with tris(1-pyrazolyl)methane (tpm) and 2,2'
      bipyridine (bpy) coligands. Structure, spectroscopy, and electrophilic and
      nucleophilic reactivities of bound nitrosyl.
AB  - The new compound [Ru(bpy)(tpm)NO](ClO4)3 [tpm = tris(1-pyrazolyl)methane; bpy =
      2,2'-bipyridine] has been prepared in a stepwise procedure that involves the
      conversion of [Ru(bpy)(tpm)Cl]+ into the aqua and nitro intermediates, followed
      by acidification. The diamagnetic complex crystallizes to exhibit distorted
      octahedral geometry around the metal, with the Ru-N(O) bond length 1.774(12) A
      and the RuNO angle 179.1(12) degrees , typical for a {RuNO}6 description. The
      [Ru(bpy)(tpm)NO]3+ ion (I) has been characterized by 1H NMR and IR spectroscopies
      (nu(NO) = 1959 cm(-1)) and through density functional theory calculations.
      Intense electronic transitions in the 300-350-nm region are assigned through time
      dependent (TD)DFT as intraligand pi --> pi for bpy and tpm. The dpi --> pi(bpy)
      metal-to-ligand charge-transfer transitions appear at higher energies. Aqueous
      cyclic voltammetric studies show a reversible wave at 0.31 V (vs Ag/AgCl, 3 M Cl
      ), which shifts to 0.60 V in MeCN, along with the onset of a wave of an
      irreversible process at -0.2 V. The waves are assigned to the one- and two
      electron reductions centered at the NO ligand, leading to species with {RuNO}(7)
      and {RuNO}(8) configurations, respectively. Controlled potential reduction of I
      in MeCN led to the [Ru(bpy)(tpm)NO]2+ ion (II), revealing a significant downward
      shift of nu(NO) to 1660 cm(-1) as well as changes in the electronic absorption
      bands. II was also characterized by electron paramagnetic resonance, showing an
      anisotropic signal at 110 K that arises from an S = 1/2 electronic ground state;
      the g-matrix components and hyperfine coupling tensor resemble the behavior of
      related {RuNO}7 complexes. Both I and II were characterized through their main
      reactivity modes, electrophilic and nucleophilic, respectively. The addition of
      OH- into I generated the nitro complex, with k(OH) = 3.05 x 10(6) M(-1) s(-1) (25
      degrees C). This value is among the highest obtained for related nitrosyl
      complexes and correlates with ENO+/NO, the one-electron redox potential. Complex
      II is a robust species toward NO release, although a conversion to I was observed
      in the presence of O2. This reaction afforded a second-order rate law with k =
      3.5 M(-1) s(-1) (25 degrees C). The stabilization of the NO radical complex is
      attributed to the high positive charge of the precursor and to the geometrical
      and electronic structure as determined by the neutral tpm ligand.

PMID- 17029372
TI  - Inorganic asymmetric synthesis: asymmetric synthesis of a two-bladed propeller,
      octahedral metal complex.
AB  - A C2 hexadentate, in which two pyridine-2-aldehyde 2'-pyridylhydrazone (PAPHY)
      groups are linked to a chiral auxiliary derived from (R,R)-tartaric acid, (R,R)
      1, reacts with iron(II) benzenesulfonate to give the two-bladed propeller,
      octahedral complex (P(Fe))-[Fe{(R,R)-1}](PhSO3)2 with complete
      diastereoselectivity, as determined by 1H NMR spectroscopy and X-ray
      crystallography. Saponification of the ester linkages and deprotonation of the
      hydrazone-NH groups in the configurationally pure diastereomer affords the
      complex (P(Fe))-[Fe(5-HOCH2PAPY)2] with 85% retention of configuration at the
      iron stereocenter, as determined by reprotonation of the neutral complex with
      enantiomerically pure (aR)-binaphthyl phosphoric acid and analysis of the 1H NMR
      spectrum of the mixture of diastereomeric salts produced. This is the first
      asymmetric synthesis of a two-bladed propeller, octahedral metal complex by the
      classical organic methodology of chiral auxiliary-directed, asymmetric synthesis.

PMID- 17029370
TI  - Pseudotetrahedral manganese complexes supported by the anionic
      tris(phosphino)borate ligand [PhBP(iPr)3].
AB  - This paper presents aspects of the coordination chemistry of mono- and divalent
      manganese complexes supported by the anionic tris(phosphino)borate ligand,
      [PhBP(i)(Pr)3] (where [PhBP(i)(Pr)3] = [PhB(CH(2)P(i)Pr2)3]-). The Mn(II) halide
      complexes, [PhBP(i)(Pr)3]MnCl (1) and [PhBP(i)(Pr)3]MnI (2), have been
      characterized by X-ray diffraction, SQUID magnetometry, and EPR spectroscopy.
      Compound 2 serves as a precursor to a series of Mn azide, alkyl, and amide
      species: [PhBP(i)(Pr)3]Mn(N3) (3), [PhBP(i)(Pr)3]Mn(CH2Ph) (4),
      [PhBP(i)(Pr)3]Mn(Me) (5), [PhBP(i)(Pr)3]Mn(NH(2,6-(i)Pr2-C6H3)) (6),
      [PhBP(i)(Pr)3]Mn(dbabh) (7), and [PhBP(i)(Pr)3]Mn(1-Ph(isoindolate)) (8). The
      complexes 2-8 feature a divalent-metal center and are pseudotetrahedral. They
      collectively represent an uncommon structural motif for low-coordinate,
      polyphosphine-supported Mn complexes. Two Mn(I) species have also been prepared.
      These include the Tl-Mn adduct [PhBP(i)(Pr)3]Tl-MnBr(CO)4 (9) and the octahedral
      complex [PhBP(i)(Pr)3]Mn(CN(t)Bu)3 (10). Some of our initial synthetic efforts to
      generate [PhBP(i)(Pr)3]MnN(x) species are briefly described, as are DFT studies
      that probe the electronic viability of these types of multiply bonded target
      structures.

PMID- 17029373
TI  - Formation of p-phenylenediamine-crown ether-[PMo12O40]4- salts.
AB  - Electron transfer from the electron donor of p-phenylenediamine (PPD) to the
      electron acceptor of (H+)3[PMo12O40]3- forms a one-electron-reduced Keggin
      cluster of [PMo12O40]4-, bearing a S = 1/2 spin, while proton transfer from the
      proton donor of (H+)3[PMo12O40]3- to the proton acceptor of PPD yielded mono- and
      diprotonated cations of 4-aminoanilinium (HPPD+) and p-phenylenediammonium
      (H2PPD2+). By introduction of crown ether receptors during the crystallization
      process, supramolecular cations of (HPPD+)(crown ethers) and/or (H2PPD2+)(crown
      ethers) were successfully introduced into three new alpha-[PMo12O40]4- salts of
      (H2PPD2+)2([12]crown-4)4[PMo12O40]4- (1), (HPPD+)4([15]crown-5)4[PMo12O40]4- (2),
      and (HPPD+)2(H2PPD2+)([18]crown-6)4[PMo12O40]4- (3) as the countercation. The
      protonated states of PPD and molecular-assembly structures of the supramolecular
      cations depended on the size of the crown ethers. In salt 3, a novel mixed
      protonated state of HPPD+ and H2PPD2+ was confirmed to be complexed in the cation
      structure. According to the changes in the cation structures, the anion
      arrangements were modulated from those of the two-dimensional layer for salt 1 to
      the isolated cluster for salts 2 and 3. The temperature-dependent magnetic
      susceptibilities of salts 1-3 were consistent with the isolated spin arrangements
      of [PMo12O40]4-. The electronic spectra of salts 1-3 indicated the intervalence
      optical transition from pentavalent Mo(V) to hexavalent Mo(VI) ions within the
      [PMo12O40]4- cluster. Temperature-dependent electron spin resonance spectra of
      salt 2 revealed the delocalization-localization transition of the S = 1/2 spin at
      60 K. The spin on the [PMo12O40]4- cluster was localized on a specific Mo(V) site
      below 60 K, which was thermally activated with an activation energy of 0.015 eV.

PMID- 17029374
TI  - Syntheses, structures, and nonlinear optical properties of heteroselenometallic W
      Se-Ag cluster compounds containing phosphine ligands.
AB  - Treatment of [Et4N]2[WSe4] with a 1:1 mixture of AgNO3 and PCy3 (Cy = cyclohexyl)
      in the absence of iodide afforded a linear trinuclear compound [(mu
      WSe4)(AgPCy3)2] (1). A similar reaction in the presence of iodide gave rise to
      the isolation of the cubanelike compound [(mu3-WSe4)Ag3(PCy3)3(mu3-I)] (2).
      Treatment of [Et4N]2[WSe4] with AgI in the presence of bidentate phosphine
      ligands bis(diphenylphosphino)amine (dppa) and bis(diphenylphosphino)methane
      (dppm) afforded the tetranuclear compounds [(mu3-WSe4)Ag3(mu-I)(mu-dppa)2] (3)
      and [(mu3-WSe4)Ag3(mu3-I)(mu-dppm)2] (4), respectively, which exhibit an open
      butterfly configuration. A novel hexanuclear cluster compound [(mu3-WSe4)2Ag4(mu
      dppm)3] (5) was obtained from interaction of [Et4N]2[WSe4] with AgNO3 and dppm in
      the absence of iodide source. The above cluster compounds are electrically
      neutral and air-stable in both solution and the solid state and have been
      characterized by electronic, infrared, mass, and NMR spectroscopies. The solid
      state structures of five cluster compounds have been established by X-ray
      crystallography. The nonlinear optical properties of compounds 4 and 5 were
      examined by z-scan techniques with 7 ns pulses at 532 nm. The optical limiting
      effects of compounds 1, 2, 4, and 5 were determined and compared with related
      argentoselenometallic compounds.

PMID- 17029375
TI  - Infrared spectra of the M(NO)n (M = Sn, Pb; n = 1, 2) and PbNO- molecules.
AB  - Reactions of laser-ablated tin and lead atoms with nitric oxide molecules in
      solid argon and neon have been investigated using matrix-isolation infrared
      spectroscopy. In the argon experiments, absorptions at 1560.1, 1625.8, and 1486.7
      cm(-1) are assigned to the N-O stretching vibrations of the SnNO and Sn(NO)2
      molecules, and absorptions at 1541.9, 1630.0, 1481.8, and 1457.5 cm(-1) are
      assigned to the N-O stretching vibrations of the PbNO, Pb(NO)2, and PbNO-
      molecules on the basis of isotopic shifts and splitting patterns. The present
      neon experiments only produce neutral tin and lead mononitrosyls. Density
      functional theory calculations have been performed on these tin and lead
      nitrosyls. The good agreement between the experimental and calculated vibrational
      frequencies, relative absorption intensities, and isotopic shifts substantiates
      the identification of these nitrosyls from the matrix infrared spectra.

PMID- 17029376
TI  - Catalysts for monooxygenations made from polyoxometalate: an iron(V)-oxo
      derivative of the Lindqvist anion.
AB  - This work uses density functional calculations to design a new high-valent
      Fe(V)=O catalyst [Mo5O18Fe=O]3-, which is based on the Lindqvist polyoxometalate
      (Mo6O19(2-)). Because the parent species is stable to oxidative conditions, one
      may assume that the newly proposed iron-oxo species will be stable, too. The
      calculated Mossbauer spectroscopic data may be helpful toward an eventual
      identification of the species. The calculations of C-H hydroxylation and C=C
      epoxidation of propene show that, if made, [Mo5O18Fe=O]3- should be a potent
      oxidant that will be subject to strong solvent effect. Moreover, the Lindqvist
      catalyst leads to an intriguing result; the reaction that starts along an
      epoxidation pathway with C=C activation ends with a C-H hydroxylation product
      ((4)6) due to rearrangement on the catalyst. The origins of this result are
      analyzed in terms of the structure of the catalyst and the electronic
      requirements for conversion of an epoxidation intermediate to a hydroxylation
      product. Thus, if made, the [Mo5O18Fe=O]3 will be a selective C-H hydroxylation
      reagent.

PMID- 17029377
TI  - Cadmium(II) and zinc(II) complexes of S-confused thiaporphyrin.
AB  - The synthesis of 5,10,15,20-tetraphenyl-2-thia-21-carbaporphyrin [S-confused
      thiaporphyrin, (SCPH)H] was optimized. The formation of the phlorin was detected,
      which was saturated at the meso carbon adjacent to thiophene. Phlorin converted
      readily to (SCPH)H in the final oxidation process. Insertion of cadmium(II) and
      zinc(II) into S-confused thiaporphyrin yielded (SCPH)Cd(II)Cl and (SCPH)Zn(II)Cl
      complexes. The macrocycle acted as a monoanionic ligand. Three nitrogen atoms and
      the C(21)H fragment of the inverted thiophene occupied equatorial positions. The
      compensation of the metal charge required the apical chloride coordination. The
      characteristic C(21)H resonances of the inverted thiophene ring were located at
      1.71 and 1.86 ppm in the 1H NMR spectra of (SCPH)Cd(II)Cl and (SCPH)Zn(II)Cl,
      respectively. The proximity of the thiophene fragment to the metal ion induced
      direct scalar couplings between the spin-active nucleus of the metal (111/113Cd)
      and the adjacent 1H nucleus (J(CdH) = 8.97 Hz). The interaction of the metal ion
      and C(21)H also was reflected by significant changes of C(21) chemical shifts:
      (SCPH)Zn(II)Cl, 92.9 ppm and (SCPH)Cd(II)Cl, 88.2 ppm (free ligand (SCPH)H, 123.7
      ppm). The X-ray analysis performed for (SCPH)Cd(II)Cl confirmed the side-on
      cadmium-thiophene interaction. The Cd...C(21) distance (2.615(7) A) exceeded the
      typical Cd-C bond lengths, but was much shorter than the corresponding van der
      Waals contact. The density functional theory (DFT) was applied to model the
      molecular structures of zinc(II) and cadmium(II) complexes of S-confused
      thiaporphyrin. Subsequent AIM analysis demonstrated that the accumulation of
      electron density between the metal and thiophene, which is necessary to induce
      these couplings, was fairly small. A bond path linked the cadmium(II) ion to the
      proximate C(22) carbon of the thiophene.

PMID- 17029378
TI  - Porous metal-organic framework with coordinatively unsaturated Mn(II)
      sites:sorption properties for various gases.
AB  - A 3D porous metal-organic framework generating 1D channels, [Mn(NDC)(DEF)]n (1),
      has been prepared from the solvothermal reaction of Mn(II) and 2,6
      naphthalenedicarboxylic acid (H2NDC) in diethylformamide (DEF). When DEF
      molecules coordinating Mn(II), which occupy the channels, are removed from 1 by
      heating the crystal of 1 at 250 degrees C under vacuum for 18 h, structural
      change occurs as evidenced by X-ray powder diffraction patterns. Desolvated solid
      [Mn(NDC)]n (2), which contains coordinatively unsaturated Mn(II) sites, reveals
      remarkable sorption capabilities for N2, H2, CO2, and CH4 gases and exhibits type
      I sorption behavior indicative of permanent microporosity.

PMID- 17029379
TI  - Construction of 3D layer-pillared homoligand coordination polymers from a 2D
      layered precursor.
AB  - Herein, we present a new method for preparing homoligand 3D coordination
      polymers. First, a layered metal-organic framework Zn3(BDC)3(H2O)2 x 4DMF 1 (BDC
      is terephthalate, DMF is N,N-dimethylformamide) was fabricated from a H2BDC by
      liquid-liquid diffusion. Second, the layered product, 1, was used as a precursor
      to solvothermally react with further H2BDC at 140-180 degrees C, resulting in two
      products of BDC insertion into the layered structure. These are [Zn3(p-BDC)4] x
      2HPIP, 2 (HPIP is partly protonated piperazine), and [Zn3(p-BDC)3(H2BDC)] x
      (C6H15NO) x H2O x 3DMF, 3 (C6H15NO is triethylamine N-oxide). Single-crystal X
      ray diffraction shows that 2 possesses a layer-pillared structure of mu4-BDC,
      with 1D channels, while 3 has a layer-pillared structure of mu2-BDC, with 2D
      channels. N2-sorption experiments show 3 has a relatively high BET surface area
      of 750 m(2)/g. It is proposed that 2 follows the crystal growth mechanism of
      Ostwald ripening, whereas the crystal structure of 3 might be formed by an
      insertion mechanism.

PMID- 17029380
TI  - Luminescent complexes of iridium(III) containing N/?C/?N-coordinating terdentate
      ligands.
AB  - A family of bis-terdentate iridium(III) complexes is reported which contain a
      cyclometalated, N/?C[wedge]N-coordinating 1,3-di(2-pyridyl)benzene derivative.
      This coordination mode is favored by blocking competitive cyclometalation at the
      C4 and C6 positions of the ligand. Thus, 1,3-di(2-pyridyl)-4,6-dimethylbenzene
      (dpyxH) reacts with IrCl3 x 3H2O to generate a dichlorobridged dimer [Ir(dpyx
      N,C,N)Cl(mu-Cl)]2, 1. This dimer is cleaved by DMSO to give [Ir(dpyx)(DMSO)Cl2],
      the X-ray crystal structure of which is reported here, confirming the N/?C/?N
      coordination mode of dpyx. The dimer 1 can also be cleaved by a variety of other
      ligands to generate novel classes of mononuclear complexes. These include charge
      neutral bis-terdentate complexes of the form [Ir(N/?C/?N)(C/?N/?C)] and
      [Ir(N/?C/?N)(C/?N/?O)], by reaction of 1 with C/?N/?C-coordinating ligands (e.g.,
      2,6-diphenylpyridine and derivatives) and C/?N/?O-coordinating ligands (based on
      6-phenylpicolinate), respectively. Treatment of 1 with terpyridines leads to
      dicationic complexes of the type [Ir(N/?C/?N)(N/?N/?N)]2+, while 2-phenylpyridine
      gives [Ir(dpyx-N/?C/?N)(ppy-C,N)Cl]. All of the charge-neutral complexes are
      luminescent in fluid solution at room temperature. Assignment of the emission to
      charge-transfer excited states with significant MLCT character is supported by
      DFT calculations. In the [Ir(N/?C/?N)(C/?N/?C)] class, fluorination of the
      C/?N/?C ligand at the phenyl 2' and 4' positions leads to a blue-shift in the
      emission and to an increase in the quantum yield (lambda(max) = 547 nm, phi =
      0.41 in degassed CH(3)CN at 295 K) compared to the nonfluorinated parent complex
      (lambda(max) = 585 nm, phi = 0.21), as well as to a stabilization of the compound
      with respect to photodissociation through cleavage of mutually trans Ir-C bonds.
      [Ir(dpyx-N/?C/?N)(ppy-C,N)Cl] is an exceptionally bright emitter: phi = 0.76,
      lambda(max) = 508 nm, in CH(3)CN at 295 K. In contrast, the
      [Ir(N/?C/?N)(C/?N/?O)] complexes are much less emissive, shown to be due to fast
      nonradiative decay of the excited state, probably involving reversible Ir-O bond
      cleavage. The [Ir(N/?C/?N)(N/?N/?N)]2+ complexes are very feeble emitters even at
      77 K, probably due to the almost exclusively interligand charge-transfer nature
      of the lowest-energy excited state in these complexes.

PMID- 17029381
TI  - Experimental and theoretical study of the coordination of 1,2,4-triazolato,
      tetrazolato, and pentazolato ligands to the [K(18-crown-6)]+ fragment.
AB  - Treatment of 3,5-diisopropyltriazole, 3,5-diphenyltriazole, 3,5-di-3
      pyridyltriazole, phenyltetrazole, pyrrolidinyltetrazole, or tert-butyltetrazole
      with equimolar quantities of potassium hydride and 18-crown-6 in tetrahydrofuran
      at ambient temperature led to slow hydrogen evolution and formation of (3,5
      diisopropyl-1,2,4-triazolato)(18-crown-6)potassium (88%), (3,5-diphenyl-1,2,4
      triazolato)(tetrahydrofuran)(18-crown-6)potassium (87%), (3,5-di-3-pyridyl-1,2,4
      triazolato)(18-crown-6)potassium (81%), (phenyltetrazolato)(18-crown-6)potassium
      (94%), (pyrrolidinyltetrazolato)(18-crown-6)potassium (90%), and (tert
      butyltetrazolato)(18-crown-6)potassium (94%) as colorless crystalline solids.
      (1,2,4-Triazolato)(18-crown-6)potassium was isolated as a hemi-hydrate in 81%
      yield upon treatment of 1,2,4-triazole with potassium metal in tetrahydrofuran.
      The X-ray crystal structures of these new complexes were determined, and the
      solid-state structures consist of the nitrogen heterocycles bonded to the (18
      crown-6)potassium cationic fragments with eta2-bonding interactions. In addition,
      (3,5-diphenyl-1,2,4-triazolato)(tetrahydrofuran)(18-crown-6)potassium has one
      coordinated tetrahydrofuran ligand on the same face as the 3,5-diphenyl-1,2,4
      triazolato ligand, while (3,5-di-3-pyridyl-1,2,4-triazolato)(18-crown-6)potassium
      forms a polymeric solid through coordination of the distal 3-pyridyl nitrogen
      atoms to the potassium ion on the face opposite the 1,2,4-triazolato ligand. The
      solid-state structures of the new complexes show variable asymmetry in the
      potassium-nitrogen distances within the eta2-interactions and also show variable
      bending of the heterocyclic C2N3 and CN4 cores toward the best plane of the 18
      crown-6 ligand oxygen atoms. Molecular orbital and natural bond order
      calculations were carried out at the B3LYP/6-311G(d,p) level of theory on the
      model complex, (phenyltetrazolato)(18-crown-6)potassium, and demonstrate that the
      asymmetric potassium-nitrogen distances and bending of the CN4 core toward the 18
      crown-6 ligand are due to hydrogen bond-like interactions between filled nitrogen
      based orbitals and carbon-hydrogen sigma orbitals on the 18-crown-6 ligands.
      Calculations carried out on the model pentazolato complex (pentazolato)(18-crown
      6)potassium predict a structure in which the pentazolato ligand N5 core is bent
      by 45 degrees toward the best plane of the 18-crown-6 oxygen atoms. Such bending
      is induced by the formation of intramolecular nitrogen-hydrogen-carbon hydrogen
      bonds. Examination of the solid-state structures of the new complexes reveals
      many intramolecular and intermolecular nitrogen-hydrogen distances of < or =3.0 A
      which support the presence of nitrogen-hydrogen-carbon hydrogen bonds.

PMID- 17029382
TI  - Homoleptic zinc(II) complexes with first and second coordination shells of 5-tert
      butylpyrazole.
AB  - Reaction of hydrated Zn[NO3]2 or Zn[BF4]2 with four or more equivalents of 3{5}
      tert-butylpyrazole (L(tBu)) yields [Zn(L(tBu))4]X2 (X- = NO3- or BF4-). The
      nitrate complex contains C2-symmetric four-coordinate zinc(II) centers with a
      slightly flattened tetrahedral geometry, and each nitrate anion hydrogen bonds to
      two pyrazole N-H groups. Similar reactions with Zn[ClO4]2 or ZnCl2 in the
      presence of 2 equiv of AgPF6 or AgSbF6 yield instead
      [{Zn(L(tBu))4}(L(tBu))4][ClO4]2 and [{Zn(L(tBu))4}(L(tBu))2]Y2 (Y- = PF6- or SbF6
      ). Crystals of [{Zn(L(tBu))4}(L(tBu))4][ClO4]2 are composed of discrete
      [{Zn(L(tBu))4}(L(tBu))4]2+ supramolecules that are formed from N-H...N hydrogen
      bonding between zinc-bound and uncoordinated pyrazole rings. The
      [{Zn(L(tBu))4}(L(tBu))4]2+ moieties are linked into planar 4(4) nets by hydrogen
      bonding to bridging ClO4- anions. The ClO4- ions are almost perfectly
      encapsulated in near-spherical cavities of approximate dimensions 5.0 x 5.0 x 4.5
      A that are formed by two interlocked supramolecular dications. Similarly,
      [{Zn(L(tBu))4}(L(tBu))2][PF6]2 crystallizes as discrete supramolecules in the
      crystal with the PF6- anions occupying a shallow bowl-shaped cavity on the
      surface of the complex that is formed by two zinc-bound and one uncoordinated
      pyrazole ligands. (1)H NMR and IR studies of [{Zn(L(tBu))4}(L(tBu))4][ClO4]2 in
      CD2Cl2 imply that the second-sphere L(tBu) ligands dissociate from the
      [Zn(L(tBu))4]2+ center in this solvent and that free and metal-bound L(tBu) are
      in rapid chemical exchange.

PMID- 17029383
TI  - Pyridine- and phosphonate-containing ligands for stable Ln complexation.
      Extremely fast water exchange on the Gd(III) chelates.
AB  - Two novel ligands containing pyridine units and phosphonate pendant arms, with
      ethane-1,2-diamine (L2) or cyclohexane-1,2-diamine (L3) backbones, have been
      synthesized for Ln complexation. The hydration numbers obtained from luminescence
      lifetime measurements in aqueous solutions of the Eu(III) and Tb(III) complexes
      are q = 0.6 (EuL2), 0.7 (TbL2), 0.8 (EuL3), and 0.4 (TbL3). To further assess the
      hydration equilibrium, we have performed a variable-temperature and -pressure UV
      vis spectrophotometric study on the Eu(III) complexes. The reaction enthalpy,
      entropy, and volume for the hydration equilibrium EuL <--> EuL(H2O) were
      calculated to be DeltaH degrees = -(11.6 +/- 2) kJ mol(-1), DeltaS degrees = 
      (34.2 +/- 5) J mol(-1) K(-1), and = 1.8 +/- 0.3 for EuL2 and DeltaH degrees = 
      (13.5 +/- 1) kJ mol(-1), DeltaS degrees = -(41 +/- 4) J mol(-1) K(-1), and = 1.7
      +/- 0.3 for EuL3, respectively. We have carried out variable-temperature 17O NMR
      and nuclear magnetic relaxation dispersion (NMRD) measurements on the GdL2(H2O)q
      and GdL3(H2O)q systems. Given the presence of phosphonate groups in the ligand
      backbone, a second-sphere relaxation mechanism has been included for the analysis
      of the longitudinal (17)O and (1)H NMR relaxation rates. The water exchange rate
      on GdL2(H2O)q, = (7.0 +/- 0.8) x 10(8) s(-1), is extremely high and comparable to
      that on the Gd(III) aqua ion, while it is slightly reduced for GdL3(H2O)q, = (1.5
      +/- 0.1) x 10(8) s(-1). This fast exchange can be rationalized in terms of a very
      flexible inner coordination sphere, which is slightly rigidified for L3 by the
      introduction of the cyclohexyl group on the amine backbone. The water exchange
      proceeds via a dissociative interchange mechanism, evidenced by the positive
      activation volumes obtained from variable-pressure 17O NMR for both GdL2(H2O)q
      and GdL3(H2O)q (DeltaV = +8.3 +/- 1.0 and 8.7 +/- 1.0 cm(3) mol(-1),
      respectively).

PMID- 17029384
TI  - Theoretical insight into electronic structures and spectroscopic properties of
      [Pt2(pop)4]4-, [Pt2(pcp)4]4-, and related derivatives (pop = P2O5H2(2-) and pcp =
      P2O4CH4(2-)).
AB  - The structures of [Pt2(pop)4]4-, [Pt2(pcp)4]4-, and related species
      [Pt2(pop)4X2]4- and [Pt2(pop)4]2- in the ground states (pop = P2O5H2(2-), pcp =
      P2O4CH4(2-), and X = I, Br, and Cl) were optimized using the second-order Moller
      Plesset perturbation (MP2) method. It is shown that the Pt-Pt distances decrease
      in going from [Pt2(pop)4]4- to [Pt2(pop)4X2]4- to [Pt2(pop)4]2-. This is
      supported by the analyses of their electronic structures. The calculated aqueous
      absorption spectra at the time-dependent density functional theory (TD-DFT) level
      agree with experimental observations. The unrestricted MP2 method was employed to
      optimize the structures of [Pt2(pop)4]4- and [Pt2(pcp)4]4- in the lowest-energy
      triplet excited states. The Pt-Pt contraction trend is well reproduced in these
      calculations. For [Pt2(pop)4]4-, the Pt-Pt distance decreases from 2.905 A in the
      ground state to 2.747 A in the excited state, which is comparable to experimental
      values of 2.91-2.92 A and 2.64-2.71 A, respectively. On the basis of the excited
      state structures of such complexes, TD-DFT predicts the solution emissions at 480
      and 496 nm, which is closer to the experimental values of 512 and 510 nm
      emissions, respectively.

PMID- 17029385
TI  - Reversible cation/anion extraction from K2La2Ti3O10: formation of new layered
      titanates, KLa2Ti3O9.5 and La2Ti3O9.
AB  - A new soft-chemical transformation of layered perovskite oxides is described
      wherein K2O is sequentially extracted from the Ruddlesden-Popper (R-P) phase,
      K2La2Ti3O10 (I), yielding novel anion-deficient KLa2Ti3O(9.5) (II) and La2Ti3O9
      (III). The transformation occurs in topochemical reactions of the R-P phase I
      with PPh4Br and PBu4Br (Ph = phenyl; Bu = n-butyl). The mechanism involves the
      elimination of KBr accompanied by decomposition of PR4+ (R = phenyl or n-butyl)
      that extracts oxygen from the titanate. Analysis of the organic products of
      decomposition reveals formation of Ph3PO, Ph3P, and Ph-Ph for R = phenyl, and
      Bu3PO, Bu3P along with butane, butene, and octane for R = butyl. The inorganic
      oxides II and III crystallize in tetragonal structures (II: P4/mmm, a = 3.8335(1)
      A, c = 14.334(1) A; III: I4/mmm, a = 3.8565(2) A, c = 24.645(2) A) that are
      related to the parent R-P phase. II is isotypic with the Dion-Jacobson phase,
      RbSr2Nb3O10, while III is a unique layered oxide consisting of charge-neutral
      La2Ti3O9 anion-deficient perovskite sheets stacked one over the other without
      interlayer cations. Interestingly, both II and III convert back to the parent R-P
      phase in a reaction with KNO3. While transformations of the R-P phases to other
      related layered/three-dimensional perovskite oxides in ion
      exchange/metathesis/dehydration/reduction reactions are known, the simultaneous
      and reversible extraction of both cations and anions in the conversions
      K2La2Ti3O10 right harpoon over left harpoon KLa2Ti3O9.5 right harpoon over left
      harpoon La2Ti3O9 is reported here for the first time.

PMID- 17029386
TI  - Synthesis, characterization, and UV-vis linear absorption of centrosymmetric pi
      systems incorporating closo-dodecaborate clusters.
AB  - Single- and multibranched centrosymmetric derivatives incorporating B12 clusters
      [B12H11-N(H)=C(H)-C6H4-C6H4-C(H)=(H)N-B12H11]2- (3) and [1,3,5-(4-(B12H11
      N(H)=C(H))-C6H4)-C6H3]3- (5) have been synthesized. Both derivatives were
      characterized by multinuclear NMR and ESI-MS analyses. To the best of our
      knowledge, compound 5 is the first example of a multicage derivative bearing
      three B12 units. Compounds 3 and 5 are only slightly yellowish colored. The UV
      vis absorption curves of 3 and 5 show intense absorption bands at 360 and 314 nm,
      respectively. This result permits us to confirm the strong donor effect of the
      B12 cluster. The hypsochrome effect observed for compound 5 compared to that of
      compound 3 confirms the interest in multibranched derivatives for the preparation
      of two-photon absorption materials active in the visible range.

PMID- 17029387
TI  - A dehydrogenation mechanism of metal hydrides based on interactions between
      Hdelta+ and H-.
AB  - This paper describes a reaction mechanism that explains the dehydrogenation
      reactions of alkali and alkaline-earth metal hydrides. These light metal
      hydrides, e.g., lithium-based compounds such as LiH, LiAlH4, and LiNH2, are the
      focus of intense research recently as the most promising candidate materials for
      on-board hydrogen storage applications. Although several interesting and
      promising reactions and materials have been reported, most of these reported
      reactions and materials have been discovered by empirical means because of a
      general lack of understanding of any underlying principles. This paper describes
      an understanding of the dehydrogenation reactions on the basis of the interaction
      between negatively charged hydrogen (H-, electron donor) and positively charged
      hydrogen (Hdelta+, electron acceptor) and experimental evidence that captures and
      explains many observations that have been reported to date. This reaction
      mechanism can be used as a guidance for screening new material systems for
      hydrogen storage.

PMID- 17029388
TI  - Phosphorus-nitrogen compounds. Part 13. Syntheses, crystal structures,
      spectroscopic, stereogenic, and anisochronic properties of novel spiro-ansa-spiro
      , spiro-bino-spiro-, and spiro-crypta phosphazene derivatives.
AB  - The condensation reactions of N2Ox (x = 2, 3) donor-type aminopodand (4) and
      dibenzo-diaza-crown ethers (5, 6, and 9) with hexachlorocyclotriphosphazatriene,
      N3P3Cl6, produce two kinds of partially substituted novel phosphazene
      derivatives, namely, spiro-bino-spiro- (19) and spiro-crypta (21, 22, and 25)
      phosphazenes. The partially substituted spiro-ansa-spiro-phosphazene (11) reacted
      with pyrrolidine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) give the
      corresponding new fully substituted phosphazenes (14 and 16). Unexpectedly, the
      reactions of 23 and 24 with pyrrolidine result in only geminal crypta
      phosphazenes (26 and 27). The solid-state structures of 16 and 22 have been
      determined by X-ray diffraction techniques. The relative inner hole-size of the
      macrocycle in the radii of 22 is 1.27 A. The relationship between the exocyclic
      NPN (alpha') and endocyclic (alpha) bond angles for spiro-crypta phosphazenes and
      exocyclic OPN (alpha') bond angles for spiro-ansa-spiro- and spiro-bino-spiro
      phosphazenes with 31P NMR chemical shifts of NPN and OPN phosphorus atoms,
      respectively, have been investigated. The structures of 10, 14, 16, 19, 21, 22,
      and 25-27 have also been examined by FTIR, 1H, 13C, and 31P NMR, HETCOR, MS, and
      elemental analyses. The 31P NMR spectra of 10, 21, 22, and 25 indicate that the
      compounds have anisochrony. In compounds 16 and 22, the spirocyclic nitrogen
      atoms have pyramidal geometries resulting in stereogenic properties.

PMID- 17029390
TI  - Isomerization processes on mixed ortho-metalated phosphine/succinimidato
      [Rh2(P(C5CH4)Ph2)2(OC4NH4O)2] complexes. A sliding movement of the succinimidato
      ligand.
AB  - An improved preparation of mixed ortho-metalated phosphine/succinimidato
      dirhodium(II) complexes, [Rh2(P(C5CH4)Ph2)2(OC4NH4O)2], allowed the isolation and
      characterization of a new isomeric form having both imidato N donors trans to P,
      1', that adds up to the two already known having both, 1, or only one, 2, of the
      imidato N donors trans to the metalated C (Chart 3). The new complex, 1',
      isomerizes to the thermodynamically stable complex 2 similarly to what had
      already been observed for isomer 1. Stoichiometric and kineticomechanistic
      studies of both isomerization processes have been carried out. The reactions have
      been shown to occur via an intramolecular dissociatively activated process,
      despite the involvement of the labile axial Rh2 coordination sites in the
      formation of intermolecular adducts in solution that do not affect the processes.
      Density functional theory calculations show two transition states with similar
      energies for the isomerizations, in very good agreement with the
      kineticomechanistic measurements. The calculation of the charge generation in the
      two distinct transition states, TS1 and TS1', indicates an important increase in
      the N negative charge from the reactants, more pronounced for TS1'. This fact
      agrees very well with the acceleration observed for the processes in polar
      solvents, especially for the 1' to 2 reaction, when compared that for the
      reactions carried out in toluene.

PMID- 17029389
TI  - Kinetics and mechanisms of chlorine dioxide and chlorite oxidations of cysteine
      and glutathione.
AB  - Chlorine dioxide oxidation of cysteine (CSH) is investigated under pseudo-first
      order conditions (with excess CSH) in buffered aqueous solutions, p[H+] 2.7-9.5
      at 25.0 degrees C. The rates of chlorine dioxide decay are first order in both
      ClO2 and CSH concentrations and increase rapidly as the pH increases. The
      proposed mechanism is an electron transfer from CS- to ClO2 (1.03 x 10(8) M(-1)
      s(-1)) with a subsequent rapid reaction of the CS* radical and a second ClO2 to
      form a cysteinyl-ClO2 adduct (CSOClO). This highly reactive adduct decays via two
      pathways. In acidic solutions, it hydrolyzes to give CSO(2)H (sulfinic acid) and
      HOCl, which in turn rapidly react to form CSO3H (cysteic acid) and Cl-. As the pH
      increases, the (CSOClO) adduct reacts with CS- by a second pathway to form
      cystine (CSSC) and chlorite ion (ClO2-). The reaction stoichiometry changes from
      6 ClO2:5 CSH at low pH to 2 ClO2:10 CSH at high pH. The ClO2 oxidation of
      glutathione anion (GS-) is also rapid with a second-order rate constant of 1.40 x
      10(8) M(-1) s(-1). The reaction of ClO2 with CSSC is 7 orders of magnitude slower
      than the corresponding reaction with cysteinyl anion (CS-) at pH 6.7. Chlorite
      ion reacts with CSH; however, at p[H+] 6.7, the observed rate of this reaction is
      slower than the ClO2/CSH reaction by 6 orders of magnitude. Chlorite ion oxidizes
      CSH while being reduced to HOCl, which in turn reacts rapidly with CSH to form Cl
      . The reaction products are CSSC and CSO3H with a pH-dependent distribution
      similar to the ClO2/CSH system.

PMID- 17029391
TI  - Synthesis and coordination behavior of planar-chiral ferrocene alkenylphosphines.
AB  - A series of planar-chiral ferrocene alkenylphosphines, (S(p))-2
      (diphenylphosphino)-1-vinylferrocene (2), (S(p))-2-(diphenylphosphino)-1-(prop-1
      en-1-yl)ferrocene (3; as a mixture of Z and E isomers in ca. 5:1 ratio), and
      (E,S(p))-2-(diphenylphosphino)-1-(2-phenylethen-1-yl)ferrocene ((E)-4), was
      obtained by Wittig and Horner-Wadsworth-Emmons reactions from the common
      precursor, (S(p))-2-(diphenylphosphino)ferrocene-1-carboxaldehyde (1).
      Coordination properties of these novel ferrocene donors were studied in their
      palladium(II) and tungsten(0)-carbonyl complexes. The reaction between 2 and
      [{Pd(mu-Cl)(L(NC))}2] (5, L(NC) = 2-{(dimethylamino)methyl-kappaN}phenyl
      kappaC(1)) gave the bridge-cleavage product [PdCl(L(NC))(2-kappaP)] (6) while the
      reaction with [Pd(L(NC))(MeCN)2]ClO4 (7) yielded the cationic bis(chelate)
      [Pd(L(NC))(2-eta2:kappaP)]ClO4 (8). Chelate complexes of the type [W(CO)4(L
      eta2:kappaP)] (9 with L = 2; (Z/E)-10 with L = (Z/E)-3) were obtained by reacting
      [W(CO)4(cod)] (cod = eta2:eta2-cycloocta-1,5-diene) with the appropriate
      phosphinoalkene in refluxing toluene while a similar reaction with (E)-4 yielded
      mixtures of [W(CO)5(4-kappaP)] ((E)-11) and [W(CO)4(4-eta2:kappaP)] ((E)-12). All
      compounds were characterized by spectral methods (multinuclear NMR, IR, MS, and
      CD), and the structures of 1, 2, 8, 9, (Z/E)-10, and (E)-11 were corroborated by
      X-ray diffraction analysis. Ligands 2 and (E)-4 as well as their complexes 6, 8,
      9, (E)-11, and (E)-12 were further studied by electrochemical methods.

PMID- 17029392
TI  - Mononitrosyl tris(thiolate) iron complex [Fe(NO)(SPh)3]- and dinitrosyl iron
      complex [(EtS)2Fe(NO)2]-: formation pathway of dinitrosyl iron complexes (DNICs)
      from nitrosylation of biomimetic rubredoxin [Fe(SR)4]2-/1- (R = Ph, Et).
AB  - Nitrosylation of the biomimetic reduced- and oxidized-form rubredoxin [Fe(SR)4]2
      /1- (R = Ph, Et) in a 1:1 stoichiometry led to the formation of the extremely air
      and light-sensitive mononitrosyl tris(thiolate) iron complexes (MNICs)
      [Fe(NO)(SR)3]- along with byproducts [SR]- or (RS)2. Transformation of
      [Fe(NO)(SR)3]- into dinitrosyl iron complexes (DNICs) [(RS)2Fe(NO)2]- and
      Roussin's red ester [Fe2(mu-SR)2(NO)4] occurs rapidly under addition of 1 equiv
      of NO(g) and [NO]+, respectively. Obviously, the mononitrosyl tris(thiolate)
      complex [Fe(NO)(SR)3]- acts as an intermediate when the biomimetic oxidized- and
      reduced-form rubredoxin [Fe(SR)4]2-/1- exposed to NO(g) were modified to form
      dinitrosyl iron complexes [(RS)2Fe(NO)2]-. Presumably, NO binding to the electron
      deficient [Fe(III)(SR)4]- and [Fe(III)(NO)(SR)3]- complexes triggers reductive
      elimination of dialkyl/diphenyl disulfide, while binding of NO radical to the
      reduced-form [Fe(II)(SR)4]2- induces the thiolate-ligand elimination. Protonation
      of [Fe(NO)(SEt)3]- yielding [Fe(NO)(SPh)3]- by adding 3 equiv of thiophenol and
      transformation of [Fe(NO)(SPh)3]- to [Fe(NO)(SEt)3]- in the presence of 3 equiv
      of [SEt]-, respectively, demonstrated that complexes [Fe(NO)(SPh)3]- and
      [Fe(NO)(SEt)3]- are chemically interconvertible. Mononitrosyl tris(thiolate) iron
      complex [Fe(NO)(SPh)3]- and dinitrosyl iron complex [(EtS)2Fe(NO)2]- were
      isolated and characterized by X-ray diffraction. The mean NO bond distances of
      1.181(7) A (or 1.191(7) A) in complex [(EtS)2Fe(NO)2]- are nearly at the upper
      end of the 1.178(3)-1.160(6) A for the anionic {Fe(NO)2}9 DNICs, while the mean
      FeN(O) distances of 1.674(6) A (or 1.679(6) A) exactly fall in the range of
      1.695(3)-1.661(4) A for the anionic {Fe(NO)2}9 DNICs.

PMID- 17029393
TI  - Aluminumoxyhydride: improved synthesis and application as a selective reducing
      agent.
AB  - Aluminumoxyhydride (HAlO) has been obtained by the reaction of aluminum hydride
      with the siloxane (Me2HSi)2O or the stannoxane (Bu3Sn)2O as an amorphous
      colorless insoluble powder. The highest-purity product resulted from the reaction
      of H3Al.NMe3 with (Me2HSi)2O. However, HAlO suspensions in tetrahydrofuran (THF)
      of sufficient quality for synthetic applications can be prepared from
      commercially available reagents with only minor precautions. A LiAlH4 solution in
      THF was treated successively with Me3SiCl and (Me2HSi)2O, followed by heating at
      60 degrees C for 20 h. The resulting suspensions are 0.4-0.5 M in active hydride
      content and selectively reduce aldehydes and ketones to the respective alcohols
      in the presence of any other common nonprotic functional group.

PMID- 17029395
TI  - On the seeding and oligomerization of pGlu-amyloid peptides (in vitro).
AB  - Oligomerization of amyloid beta (Abeta) peptides is the decisive event in the
      development of Alzheimer's disease (AD), the most common neurogenerative disorder
      in developed countries. Recent evidence links this conformation-driven process to
      primary- and secondary-structure modifications of Abeta. The N and C terminus of
      deposited Abeta has been shown to possess conspicuous heterogeneity. While the C
      terminally longer form of Abeta, i.e., Abeta (42), is considered more
      amyloidogenic, the role of the N-terminal modifications, e.g., truncation and
      glutamate cyclization accounting for the majority of the deposited peptides, is
      less understood. In the present study, we characterized the oligomerization and
      seeding capacity of pGlu-amyloid peptides using two unrelated techniques based on
      flow cytometry or flourescence dye binding. Under different conditions and
      irrespective of the C terminus of Abeta, i.e., Abeta40 or 42, pGlu-modified
      peptides displayed an up to 250-fold accelerated initial formation of aggregates
      compared to unmodified Abeta. The accelerated seed formation is accompanied by a
      change in the oligomerization kinetics because of N-terminal pGlu formation.
      Furthermore, the formation of mixed aggregates consisting of either pGlu-Abeta (3
      42) or ADan or ABri and Abeta (1-42) was investigated by Abeta fluorescence
      labeling in flow cytometry. The results suggest that pGlu-modified peptides are
      potential seeding species of aggregate formation in vivo. The data presented here
      and the abundance of pGlu peptides in amyloidoses, such as FBD and AD, suggest
      pGlu-amyloid peptides as a species with biophysical characteristics that might be
      in particular crucial for the initiation of the disease.

PMID- 17029396
TI  - Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites.
      1. Quantification of hemozoin development for drug sensitive versus resistant
      malaria.
AB  - We have customized a Nipkow spinning disk confocal microscope (SDCM) to acquire
      three-dimensional (3D) versus time data for live, intraerythrocytic malarial
      parasites. Since live parasites wiggle within red blood cells, conventional laser
      scanning confocal microscopy produces blurred 3D images after reconstruction of z
      stack data. In contrast, since SDCM data sets at high x, y, and z resolution can
      be acquired in hundreds of milliseconds, key aspects of live parasite cellular
      biochemistry can be much better resolved on physiologically meaningful times
      scales. In this paper, we present the first 3D DIC transmittance "z stack" images
      of live malarial parasites and use those to quantify hemozoin (Hz) produced
      within the living parasite digestive vacuole, under physiologic conditions. Using
      live synchronized cultures and voxel analysis of sharpened DIC z stacks, we
      present the first quantitative in vivo analysis of the rate of Hz growth for
      chloroquine sensitive (CQS) versus resistant (CQR) malarial parasites. We present
      data for laboratory strains, as well as pfcrt transfectants expressing a CQR
      conferring mutant pfcrt gene. We also analyze the rate of Hz growth in the
      presence and absence of physiologically relevant doses of chloroquine (CQ) and
      verapamil (VPL) and thereby present the first in vivo quantification of key
      predictions from the well-known Fitch hypothesis for CQ pharmacology. In the
      following paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12411
      12423], we acquire fluorescent images of live parasite DV via SDCM and use those
      to quantify DV volume for CQS versus CQR parasites.

PMID- 17029397
TI  - Spinning disk confocal microscopy of live, intraerythrocytic malarial parasites.
      2. Altered vacuolar volume regulation in drug resistant malaria.
AB  - In the previous paper [Gligorijevic, B., et al. (2006) Biochemistry 45, pp 12400
      12410], we reported on a customized Nipkow spinning disk confocal microscopy
      (SDCM) system and its initial application to DIC imaging of hemozoin within live,
      synchronized, intraerythrocytic Plasmodium falciparum malarial parasites. In this
      paper, we probe the biogenesis as well as the volume and pH regulation of the
      parasite digestive vacuole (DV), using the fluorescence imaging capabilities of
      the system. Several previous reports have suggested that mutant PfCRT protein,
      which causes chloroquine resistance (CQR) in P. falciparum, also causes increased
      acidification of the DV. Since pH and volume regulation are often linked, we
      wondered whether DV volume differences might be associated with CQR. Using fast
      acquisition of SDCM z stacks for synchronized parasites with OGd internalized
      into the DV, followed by iterative deconvolution using experimental point spread
      functions, we quantify the volume of the DV for live, intraerythrocytic HB3
      (CQS), Dd2 (CQR via drug selection), GCO3 (CQS), and GCO3/C3(Dd2) (CQR via
      transfection with mutant pfcrt) malarial parasites as they develop within the
      human red blood cell. We find that relative to both CQS strains, both CQR strains
      show significantly increased DV volume as the organelle forms upon entry into the
      trophozoite stage of development and that this persists until the trophozoite
      schizont boundary. A more acidic DV pH is found for CQR parasites as soon as the
      organelle forms and persists throughout the trophozoite stage. We probe DV volume
      and pH changes upon ATP depletion, hypo- and hypertonic shock, and rapid
      withdrawal of perfusate chloride. Taken together, these data suggest that the
      PfCRT mutations that cause CQR also lead to altered DV volume regulation.

PMID- 17029399
TI  - Isoform-specific membrane insertion of secretory phospholipase A2 and functional
      implications.
AB  - Despite increasing evidence that the membrane-binding mode of interfacial enzymes
      including the depth of membrane insertion is crucial for their function, the
      membrane insertion of phospholipase A(2) (PLA(2)) enzymes has not been studied
      systematically. Here, we analyze the membrane insertion of human group IB PLA(2)
      (hIBPLA(2)) and compare it with that of a structurally homologous V3W mutant of
      human group IIA PLA(2) (V3W-hIIAPLA(2)) and with a structurally divergent group
      III bee venom PLA(2) (bvPLA(2)). Increasing the anionic charge of membranes
      results in a blue shift of the fluorescence of Trp(3) of hIBPLA(2), a decrease in
      quenching by acrylamide, and an increase in enzyme activity, reflecting an
      enhancement in the membrane binding of PLA(2). Fluorescence quenching by
      brominated lipids indicates significant penetration of Trp(3) into fluid
      POPC/POPG membranes but little insertion into the solid DPPC/DPPG membranes.
      Increased membrane fluidity also supports hIBPLA(2) activity, suggesting that
      membrane insertion of hIBPLA(2) is controlled by membrane fluidity and is
      necessary for the full activity of the enzyme. Trp fluorescence quenching of the
      V3W-hIIAPLA(2) and bvPLA(2) by water- and membrane-soluble quenchers indicates
      substantial membrane insertion of Trp(3) of V3W-hIIAPLA(2), similar to that found
      for hIBPLA(2), and no insertion of tryptophans of bvPLA(2). Our results provide
      evidence that (a) structurally similar group IB and IIA PLA(2)s, but not
      structurally diverse group III PLA(2), significantly penetrate into membranes;
      (b) membrane insertion is controlled by membrane fluidity and facilitates
      activation of IB and IIA PLA(2)s; and (c) structurally distinct PLA(2) isoforms
      may employ different tactics of substrate accession/product release during lipid
      hydrolysis.

PMID- 17029398
TI  - Atomic force microscopy reveals DNA bending during group II intron
      ribonucleoprotein particle integration into double-stranded DNA.
AB  - The mobile Lactococcus lactis Ll.LtrB group II intron integrates into DNA target
      sites by a mechanism in which the intron RNA reverse splices into one DNA strand
      while the intron-encoded protein uses a C-terminal DNA endonuclease domain to
      cleave the opposite strand and then uses the cleaved 3' end to prime reverse
      transcription of the inserted intron RNA. These reactions are mediated by an RNP
      particle that contains the intron-encoded protein and the excised intron lariat
      RNA, with both the protein and base pairing of the intron RNA used to recognize
      DNA target sequences. Here, computational analysis indicates that Escherichia
      coli DNA target sequences that support Ll.LtrB integration have greater predicted
      bendability than do random E. coli genomic sequences, and atomic force microscopy
      shows that target DNA is bent during the reaction with Ll.LtrB RNPs. Time course
      and mutational analyses show that DNA bending occurs after reverse splicing and
      requires subsequent interactions between the intron-encoded protein and the 3'
      exon, which lead to two progressively larger bend angles. Our results suggest a
      model in which RNPs bend the target DNA by maintaining initial contacts with the
      5' exon while engaging in subsequent 3' exon interactions that successively
      position the scissile phosphate for bottom-strand cleavage at the DNA
      endonuclease active site and then reposition the 3' end of the cleaved bottom
      strand to the reverse transcriptase active site for initiation of cDNA synthesis.
      Our findings indicate that bendability of the DNA target site is a significant
      factor for Ll.LtrB RNP integration.

PMID- 17029400
TI  - Structural and functional effects of tryptophans inserted into the membrane
      binding and substrate-binding sites of human group IIA phospholipase A2.
AB  - Phospholipase A(2) (PLA(2)) enzymes become activated by binding to biological
      membranes and hydrolyze phospholipids to free fatty acids and lyso-phospholipids,
      the precursors of inflammatory mediators. To understand the functional
      significance of amino acid residues at key positions, we have studied the effects
      of the substitution of Val(3) (membrane binding surface) and Phe(5) (substrate
      binding pocket) of human group IIA PLA(2) by tryptophan on the structure and
      function of the enzyme. Despite the close proximity of the sites of mutations,
      the V3W mutation results in substantial enhancement of the enzyme activity,
      whereas the F5W mutant demonstrates significantly suppressed activity. A
      structural analysis of all three proteins free in buffer and bound to membranes
      indicates that large differences in activities result from distinct
      conformational changes in PLA(2)s upon membrane binding. Although PLA(2) and the
      V3W mutant demonstrate a decrease in helical content and an increase in helix
      flexibility, the F5W mutant experiences partial distortion of the alpha-helical
      structure presumably resulting from the tendency of Trp(5) to insert into the
      membrane. Furthermore, whereas the PLA(2) and the V3W mutant bind to the membrane
      at similar and apparently productive-mode orientation, the F5W mutant binds to
      membranes with a distinctly different orientation. It is suggested that both the
      stimulatory effect of the V3W mutation and the inhibitory effect of the F5W
      mutation result from the high affinity of Trp for the membrane-water interface.
      Although Trp(3) at the membrane binding face of PLA(2) facilitates the proper
      membrane binding of the enzyme, Trp(5) in the internal substrate binding site
      causes partial unwinding of the N-terminal helix in order to interact with the
      membrane.

PMID- 17029401
TI  - Evidence for a gem-diol reaction intermediate in bacterial C-C hydrolase enzymes
      BphD and MhpC from 13C NMR spectroscopy.
AB  - C-C hydrolase enzymes MhpC and BphD catalyze the hydrolytic C-C cleavage of meta
      ring fission intermediates on the Escherichia coli phenylpropionic acid and
      Burkholderia xenovorans LB400 biphenyl degradation pathways and are both members
      of the alpha/beta-hydrolase family containing a Ser-His-Asp catalytic triad. The
      catalytic mechanism of this family of enzymes is thought to proceed via a gem
      diol reaction intermediate, which has not been observed directly. Site-directed
      single mutants of BphD in which catalytic residues His-265 and Ser-112 were
      replaced with Ala were found to possess 10(4)-fold reduced k(cat) values, and in
      each case, the C-C cleavage step was shown by pre-steady-state kinetic analysis
      to be rate-limiting. The processing of a 6-(13)C-labeled aryl-containing
      substrate by these H265A or S112A mutant BphD enzymes was monitored directly by
      (13)C NMR spectroscopy. A new line-broadened signal was observed at 128 ppm for
      each enzyme, corresponding to the proposed gem-diol reaction intermediate, over a
      time scale of 1-24 h. A similar signal was observed upon incubation of the (13)C
      labeled substrate with an H114A MhpC mutant, which is able to accept the 6-phenyl
      containing substrate, on a shorter time scale. The direct observation of a gem
      diol intermediate provides further evidence that supports a general base
      mechanism for this family of enzymes.

PMID- 17029402
TI  - Catalytic role for arginine 188 in the C-C hydrolase catalytic mechanism for
      Escherichia coli MhpC and Burkholderia xenovorans LB400 BphD.
AB  - The alpha/beta-hydrolase superfamily, comprised mainly of esterase and lipase
      enzymes, contains a family of bacterial C-C hydrolases, including MhpC and BphD
      which catalyze the hydrolytic C-C cleavage of meta-ring fission intermediates on
      the Escherichia coli phenylpropionic acid pathway and Burkholderia xenovorans
      LB400 biphenyl degradation pathway, respectively. Five active site amino acid
      residues (Arg-188, Asn-109, Phe-173, Cys-261, and Trp-264) were identified from
      sequence alignments that are conserved in C-C hydrolases, but not in enzymes of
      different function. Replacement of Arg-188 in MhpC with Gln and Lys led to 200-
      and 40-fold decreases, respectively, in k(cat); the same replacements for Arg-190
      of BphD led to 400- and 700-fold decreases, respectively, in k(cat). Pre-steady
      state kinetic analysis of the R188Q MhpC mutant revealed that the first step of
      the reaction, keto-enol tautomerization, had become rate-limiting, indicating
      that Arg-188 has a catalytic role in ketonization of the dienol substrate, which
      we propose is via substrate destabilization. Mutation of nearby residues Phe-173
      and Trp-264 to Gly gave 4-10-fold reductions in k(cat) but 10-20-fold increases
      in K(m), indicating that these residues are primarily involved in substrate
      binding. The X-ray structure of a succinate-H263A MhpC complex shows concerted
      movements in the positions of both Phe-173 and Trp-264 that line the approach to
      Arg-188. Mutation of Asn-109 to Ala and His yielded 200- and 350-fold reductions,
      respectively, in k(cat) and pre-steady-state kinetic behavior similar to that of
      a previous S110A mutant, indicating a role for Asn-109 is positioning the active
      site loop containing Ser-110. The catalytic role of Arg-188 is rationalized by a
      hydrogen bond network close to the C-1 carboxylate of the substrate, which
      positions the substrate and promotes substrate ketonization, probably via
      destabilization of the bound substrate.

PMID- 17029403
TI  - Metal-linked dimerization in the iron-dependent regulator from Mycobacterium
      tuberculosis.
AB  - The iron-dependent regulator (IdeR) is a 230-amino acid transcriptional repressor
      that regulates iron homeostasis, oxidative stress response and virulence in
      Mycobacterium tuberculosis. The natural ligand for IdeR is Fe(II), but Ni(II),
      Co(II), Cd(II), Mn(II), and Zn(II) also bind to and activate the protein in
      vitro. Protein activation by metal is a complex process involving metal-induced
      folding of the N-terminal domain, changes in the interaction between the N- and C
      terminal domains, and the formation of homodimers. Here, we investigate the
      energetics of dimerization and metal binding in IdeR. The dimerization energetics
      were determined as a function of metal binding using equilibrium analytical
      ultracentrifugation. The equilibrium dimer dissociation constant of apo-IdeR was
      4.0 microM at 20 degrees C. The dissociation constant decreased to 0.5 microM in
      the presence of one equivalent of Ni(II)Cl(2) and decreased further (K(d) << 50
      nM) in the presence of excess Ni(II). IdeR contains two tryptophan residues. The
      addition of Ni(II) induced changes in fluorescence intensity and emission maximum
      of the tryptophan residues that strongly depended on protein concentration. At
      low IdeR concentration, fluorescence was enhanced at low metal-to-protein ratios
      but was quenched at high metal-to-protein ratios. At high IdeR concentration,
      metal binding resulted only in fluorescence quenching. The fluorescence
      enhancement at low protein concentrations was buffer-dependent and required the
      presence of both tryptophans. Metal binding affinity was measured quantitatively
      using equilibrium dialysis. The results showed strongly positive cooperative
      binding of three equivalents of metal per monomer with an average apparent
      dissociation constant of 2.2 +/- 0.3 microM and a Hill coefficient of 2. Metal
      binding was not cooperative in an IdeR variant that showed reduced affinity for
      dimer formation. The results of this study establish the positive cooperative
      nature of metal binding by IdeR and suggest that dimerization is a major
      contributor to cooperative binding. The strong coupling between metal binding and
      dimerization places specific constraints on the activation mechanism.

PMID- 17029404
TI  - Identification of tyrosine 79 in the tocopherol binding site of glutathione S
      transferase pi.
AB  - Alpha-tocopherol, the most abundant form of vitamin E present in humans, is a
      noncompetitive inhibitor of glutathione S-transferase pi (GST pi), but its
      binding site had not been located. Tocopherol iodoacetate (TIA), a reactive
      analogue, produces a time-dependent inactivation of GST pi to a limit of 25%
      residual activity. The rate constant for inactivation, k(obs), exhibits a
      nonlinear dependence on reagent concentration, with K(I) = 19 microM and k(max) =
      0.158 min(-)(1). Complete protection against inactivation is provided by
      tocopherol and tocopherol acetate, whereas glutathione derivatives, electrophilic
      substrate analogues, buffers, or nonsubstrate hydrophobic ligands have little
      effect on k(obs). These results indicate that TIA reacts as an affinity label of
      a distinguishable tocopherol binding site. Loss of activity occurs concomitant
      with incorporation of about 1 mol of reagent/mol of enzyme subunit when the
      enzyme is maximally inactivated. Isolation of the labeled peptide from the
      tryptic digest shows that Tyr(79) is the only enzymic amino acid modified. The
      Y79F, Y79S, and Y79A mutant enzymes were generated, expressed, and purified.
      Changing Tyr(79) to Ser or Ala, but not Phe, renders the enzyme insensitive to
      inhibition by either tocopherol or tocopherol acetate as demonstrated by
      increases of at least 49-fold in K(I) values as compared to the wild-type enzyme.
      These results and examination of the crystal structure of GST pi suggest that
      tocopherols bind at a novel site, where an aromatic residue at position 79 is
      essential for binding.

PMID- 17029405
TI  - The endothelium-derived hyperpolarizing factor, H2O2, promotes metal-ion efflux
      in aortic endothelial cells: elemental mapping by a hard X-ray microprobe.
AB  - Hydrogen peroxide (H(2)O(2)) is a physiologic oxidant implicated in vascular cell
      signaling, although little is known about the biochemical consequences of its
      reaction with endothelial cells. Submicrometer-resolution hard X-ray elemental
      mapping of cultured porcine aortic endothelial cells (PAEC) has provided data on
      the global changes for intracellular elemental density within PAEC and indicates
      an efflux of metal ions and phosphorus from the cytoplasm after H(2)O(2)
      treatment. The synchrotron-radiation-induced X-ray emission experiments (SRIXE)
      show that H(2)O(2)-treated cells are irregularly shaped and exhibit blebbing
      indicative of increased permeability due to the damaged membrane. The SRIXE
      results suggest that H(2)O(2)-induced damage is largely restricted to the cell
      membrane as judged by the changes to membrane and cytoplasmic components rather
      than the cell nucleus. The SRIXE data also provide a mechanism for cell
      detoxification as the metal-ion efflux resulting from the initial H(2)O(2)
      mediated changes to cell membrane potentially limits intracellular metal-mediated
      redox processes through Fenton-like chemistry. They may also explain the
      increased levels of these ions in atherosclerotic plaques, regardless of whether
      they are involved in plaque formation. Finally, the SRIXE data support the notion
      that cultured endothelial cells exposed to H(2)O(2) respond with enhanced
      cellular metal-ion efflux into the extracellular space.

PMID- 17029406
TI  - Dynamic behavior of fatty acid spin labels within a binding site of soybean
      lipoxygenase-1.
AB  - The putative substrate-binding site in lipoxygenases is long and internal. There
      is little direct evidence about how the unsaturated fatty acid substrates enter
      and move within the cavity to position themselves correctly for electron transfer
      reactions with the catalytic non-heme iron. An EPR spectroscopy approach, with
      spin-labeled fatty acids, is taken here to investigate dynamic behavior of fatty
      acids bound to soybean lipoxygenase-1. The probes are labeled on C5, C8, C10,
      C12, and C16 of stearic acid. The EPR-determined affinity for the enzyme
      increases as the length of the alkyl end of the probe increases, with a
      DeltaDeltaG of -190 cal/methylene. The probes in the series exhibit similar
      enhanced paramagnetic relaxation by the iron center. These results indicate that
      the members of the series have a common binding site. All of the bound probes
      undergo considerable local mobility. The stearate spin-labeled at C5 has the
      highest affinity for the lipoxygenase, and it is a competitive inhibitor, with a
      K(i) of 9 muM. Surprisingly, this stearate labeled near the carboxyl end
      undergoes more local motion than those labeled in the middle of the chain, when
      it is bound. This shows that the carboxyl end of the fatty-acid spin label is not
      rigidly docked on the protein. During catalysis, repositioning of the substrate
      carboxyl on the protein surface may be coupled to motion of portions of the chain
      undergoing reaction.

PMID- 17029408
TI  - Evaluating the roles of the heme a side chains in cytochrome c oxidase using
      designed heme proteins.
AB  - Heme a is a redox cofactor unique to cytochrome c oxidases and vital to aerobic
      respiration. Heme a differs from the more common heme b by two chemical
      modifications, the C-8 formyl group and the C-2 hydroxyethylfarnesyl group. The
      effects of these porphyrin substituents on ferric and ferrous heme binding and
      electrochemistry were evaluated in a designed heme protein maquette. The maquette
      scaffold chosen, [Delta7-H3m](2), is a four-alpha-helix bundle that contains two
      bis(3-methyl-l-histidine) heme binding sites with known absolute ferric and
      ferrous heme b affinities. Hemes b, o, o+16, and heme a, those involved in the
      biosynthesis of heme a, were incorporated into the bis(3-methyl-l-histidine) heme
      binding sites in [Delta7-H3m](2). Spectroscopic analyses indicate that 2 equiv of
      each heme binds to [Delta7-H3m](2), as designed. Equilibrium binding studies of
      the hemes with the maquette demonstrate the tight affinity for hemes containing
      the C-2 hydroxyethylfarnesyl group in both the ferric and ferrous forms. Coupled
      with the measured equilibrium midpoint potentials, the data indicate that the
      hydroxyethylfarnesyl group stabilizes the binding of both ferrous and ferric heme
      by at least 6.3 kcal/mol via hydrophobic interactions. The data also demonstrate
      that the incorporation of the C-8 formyl substituent in heme a results in a 179
      mV, or 4.1 kcal/mol, positive shift in the heme reduction potential relative to
      heme o due to the destabilization of ferric heme binding relative to ferrous heme
      binding. The two substituents appear to counterbalance each other to provide for
      tighter heme a affinity relative to heme b in both the ferrous and ferric forms
      by at least 6.3 and 2.1 kcal/mol, respectively. These results also provide a
      rationale for the reaction sequence observed in the biosynthesis of heme a.

PMID- 17029407
TI  - The W105G and W99G sorcin mutants demonstrate the role of the D helix in the
      Ca(2+)-dependent interaction with annexin VII and the cardiac ryanodine receptor.
AB  - Sorcin, a 21.6 kDa two-domain penta-EF-hand (PEF) protein, when activated by
      Ca(2+) binding, interacts with target proteins in a largely uncharacterized
      process. The two physiological EF-hands EF3 and EF2 do not belong to a structural
      pair but are connected by the D helix. To establish whether this helix is
      instrumental in sorcin activation, two D helix residues were mutated: W105,
      located near EF3 and involved in a network of interactions, and W99, located near
      EF2 and facing solvent, were substituted with glycine. Neither mutation alters
      calcium affinity. The interaction of the W105G and W99G mutants with annexin VII
      and the cardiac ryanodine receptor (RyR2), requiring the sorcin N-terminal and C
      terminal domain, respectively, was studied. Surface plasmon resonance experiments
      show that binding of annexin VII to W99G occurs at the same Ca(2+) concentration
      as that of the wild type, whereas W105G requires a significantly higher Ca(2+)
      concentration. Ca(2+) spark activity of isolated heart cells monitors the sorcin
      RyR2 interaction and is unaltered by W105G but is reduced equally by W99G and the
      wild type. Thus, substitution of W105, via disruption of the network of D helix
      interactions, affects the capacity of sorcin to recognize and interact with
      either target at physiological Ca(2+) concentrations, while mutation of solvent
      facing W99 has little effect. The D helix appears to amplify the localized
      structural changes that occur at EF3 upon Ca(2+) binding and thereby trigger a
      structural rearrangement that enables interaction of sorcin with its molecular
      targets. The same activation process may apply to other PEF proteins in view of
      the D helix conservation.

PMID- 17029409
TI  - Characterization of the LSGGQ and H motifs from the Escherichia coli lipid A
      transporter MsbA.
AB  - ATP-binding cassette (ABC) transporters make up one of the largest superfamilies
      of proteins known and have been shown to transport substrates ranging from lipids
      and antibiotics to sugars and amino acids. The dysfunction of ABC transporters
      has been linked to human pathologies such as cystic fibrosis, hyperinsulinemia,
      and macular dystrophy. Several bacterial ABC transporters are also necessary for
      bacterial survival and transport of virulence factors in an infected host. MsbA
      is a 65 kDa protein that forms a functional homodimer consisting of two six-helix
      transmembrane domains and two approximately 250 amino acid nucleotide-binding
      domains (NBD). The NBDs contain several conserved regions such as the Walker A,
      LSGGQ, and H motif that bind directly to ATP and align it for hydrolysis. MsbA
      transports lipid A, its native substrate, across the inner membrane of Gram
      negative bacteria. The loss or dysfunction of MsbA results in a toxic
      accumulation of lipid A inside the cell, leading to cell-membrane instability and
      cell death. Using site-directed spin labeling electron paramagnetic resonance
      spectroscopy, conserved motifs within the MsbA NBD have been evaluated for
      structure and dynamics upon substrate binding. It has been determined that the
      LSGGQ NBD consensus sequence is consistent with an alpha-helical conformation and
      that these residues maintain extensive tertiary contacts throughout hydrolysis.
      The dynamics of the LSGGQ and the H-motif region have been studied in the
      presence of ATP, ADP, and ATP plus vanadate to identify the residues that are
      directly affected by interactions with the substrate before, after, and during
      hydrolysis, respectively.

PMID- 17029411
TI  - Structural impact of heparin binding to full-length Tau as studied by NMR
      spectroscopy.
AB  - The neuronal Tau protein is involved in stabilizing microtubules but is also the
      major component of the paired helical filaments (PHFs), the intracellular
      aggregates that characterize Alzheimer's disease (AD) in neurons. In vitro, Tau
      can be induced to form AD-like aggregates by adding polyanions such as heparin.
      While previous studies have identified the microtubule binding repeats (MTBRs) as
      the major player in Tau aggregation, the fact that the full-length protein does
      not aggregate by itself indicates the presence of inhibitory factors. Charge and
      conformational changes are of uttermost importance near the second (R2) and third
      (R3) MTBR that are thought to be involved directly in the nucleation of the
      aggregation. Recently, the positively charged regions flanking the MTBR were
      proposed to inhibit PHF assembly, where hyperphosphorylation neutralizes these
      basic inhibitory domains, enabling Tau-Tau interactions. Here we present results
      of an NMR study on the interaction between intact full-length Tau and small
      heparin fragments of well-defined size, under conditions where no aggregation
      occurs. Our findings reveal (i) micromolar affinity of heparin to residues in R2
      and R3, (ii) two zones of strong interaction within the positively charged
      inhibitory regions flanking the MTBR, and (iii) another interaction site upstream
      of the two inserts encoded by exons 2 and 3. Three-dimensional heteronuclear NMR
      experiments demonstrate that the interaction with heparin induces beta-strand
      structure in several regions of Tau that might act as nucleation sites for its
      aggregation but indicate as well alpha-helical structure in regions outside the
      core of PHF. In the PHF, the residues outside of the core maintain sufficient
      mobility for NMR detection and recover their unbound chemical shift values after
      an overnight incubation at 37 degrees C with heparin. Heparin thus becomes
      integrated into the rigid core region of the PHF, probably providing the charge
      compensation for the lysine-rich stretches that form upon the in-register,
      parallel stacking of the repeat regions.

PMID- 17029412
TI  - Mechanism of the conformational transitions in 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase as revealed by NMR spectroscopy.
AB  - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer
      of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), leading to
      the biosynthesis of folate cofactors. HPPK undergoes dramatic conformational
      changes during its catalytic cycle, and the conformational changes are essential
      for enzymatic catalysis. Thus, the enzyme is not only an attractive target for
      developing antimicrobial agents but also an excellent model system for studying
      the catalytic mechanism of enzymatic pyrophosphoryl transfer as well as the role
      of protein dynamics in enzymatic catalysis. In the present study, we report the
      NMR solution structures of the binary complex HPPK*MgAMPCPP and the ternary
      complex HPPK*MgAMPCPP*DMHP, where alpha,beta-methyleneadenosine triphosphate
      (AMPCPP) and 7, 7-dimethyl-6-hydroxypterin (DMHP) are the analogues of the
      substrates ATP and HP, respectively. The results suggest that the three catalytic
      loops of the binary complex of HPPK can assume multiple conformations in slow
      exchanges as evidenced by multiple sets of NMR signals for several residues in
      loops 2 and 3 and the very weak or missing NH cross-peaks for several residues in
      loops 1 and 3. However, the ternary complex shows only one set of NMR signals,
      and the cross-peak intensities are rather uniform, suggesting that the binding of
      the second substrate shifts the multiple conformations of the binary complex to
      an apparently single conformation of the ternary complex. The NMR behaviors and
      conformations of the binary complex HPPK*MgAMPCPP are significantly different
      from those of HPPK in complex with Mgbeta,gamma-methyleneadenosine triphosphate
      (MgAMPPCP). It is suggested that the conformational properties of the binary
      substrate complex HPPK*MgATP be represented by those of HPPK*MgAMPCPP, because
      MgAMPCPP is a better MgATP analogue for HPPK with respect to both binding
      affinity and bound conformation.

PMID- 17029410
TI  - Rational design of new binding specificity by simultaneous mutagenesis of
      calmodulin and a target peptide.
AB  - Calcium-saturated calmodulin (CaM) binds and influences the activity of a varied
      collection of target proteins in most cells. This promiscuity underlies the role
      of CaM as a shared participant in calcium-dependent signal transduction pathways
      but imposes a handicap on popular CaM-based calcium biosensors, which display an
      undesired tendency to cross-react with cellular proteins. Designed CaM/target
      pairs that retain high affinity for one another but lack affinity for wild-type
      CaM and its natural interaction partners would therefore be useful as sensor
      components and possibly also as elements of "synthetic" cellular-signaling
      networks. Here, we have adopted a rational approach to creating suitably modified
      CaM/target complexes by using computational design methods to guide parallel site
      directed mutagenesis of both binding partners. A hierarchical design procedure
      was applied to suggest a small number of complementary mutations on CaM and on a
      peptide ligand derived from skeletal-muscle light-chain kinase (M13).
      Experimental analysis showed that the procedure was successful in identifying CaM
      and M13 mutants with novel specificity for one another. Importantly, the designed
      complexes retained an affinity comparable to the wild-type CaM/M13 complex. These
      results represent a step toward the creation of CaM and M13 derivatives with
      specificity fully orthogonal to the wild-type proteins and show that
      qualitatively accurate predictions may be obtained from computational methods
      applied simultaneously to two proteins involved in multiple-linked binding
      equilibria.

PMID- 17029413
TI  - Alternatively spliced exon B of myosin Va is essential for binding the tail
      associated light chain shared by dynein.
AB  - A 10 kDa dynein light chain (DLC), previously identified as a tail light chain of
      myosin Va, may function as a cargo-binding and/or regulatory subunit of both
      myosin and dynein. Here, we identify and characterize the binding site of DLC on
      myosin Va. Fragments of the human myosin Va tail and the DLC2 isoform were
      expressed, and their complex formation was analyzed by pull-down assays, gel
      filtration, and spectroscopic methods. DLC2 was found to bind as a homodimer to a
      approximately 15 residue segment (Ile1280-Ile1294) localized between the medial
      and distal coiled-coil domains of the tail. The binding region contains the three
      residues coded by the alternatively spliced exon B (Asp1284-Lys1286). Removal of
      exon B eliminates DLC2 binding. Co-localization experiments in a transfected
      mammalian cell line confirm our finding that exon B is essential for DLC2
      binding. Using circular dichroism, we demonstrate that binding of DLC2 to a
      approximately 85 residue disordered domain (Pro1235-Arg1320) induces some helical
      structure and stabilizes both flanking coiled-coil domains (melting temperature
      increases by approximately 7 degrees C). This result shows that DLC2 promotes the
      assembly of the coiled-coil domains of myosin Va. Nuclear magnetic resonance
      spectroscopy and docking simulations show that a 15 residue peptide (Ile1280
      Ile1294) binds to the surface grooves on DLC2 similarly to other known binding
      partners of DLCs. When our data are taken together, they suggest that exon B and
      its associated DLC2 have a significant effect on the structure of parts of the
      coiled-coil tail domains and such a way could influence the regulation and cargo
      binding function of myosin Va.

PMID- 17029414
TI  - Role of Asp1393 in catalysis, flavin reduction, NADP(H) binding, FAD
      thermodynamics, and regulation of the nNOS flavoprotein.
AB  - Nitric oxide synthases (NOS) are flavoheme enzymes with important roles in
      biology. The reductase domain of neuronal NOS (nNOSr) contains a widely conserved
      acidic residue (Asp(1393)) that is thought to facilitate hydride transfer between
      NADPH and FAD. Previously we found that the D1393V and D1393N mutations lowered
      the NO synthesis activity and the rates of heme and flavin reduction in full
      length nNOS. To examine the mechanisms for these results in greater detail, we
      incorporated D1393V and D1393N substitutions into nNOSr along with a truncated
      NADPH-FAD domain construct (FNR) and characterized the mutants. D1393V nNOSr had
      markedly lower (<or=1000x) cytochrome c reductase, ferricyanide reductase, and
      NADPH oxidase activities than the wild type. D1393N nNOSr also had lower
      reductase activities (<or=10x) but had greater NADPH oxidase activity than that
      of the wild type, as did its FNR fragment. Both mutants had an altered
      interaction between FAD and the nicotinamide ring of NADP(+), slower flavin
      reduction by NADPH, altered FAD midpoint potentials, a normal CaM response, and,
      in one case (D1393N), faster flavin oxidation by O(2) and a lack of FMN shielding
      in response to NADPH binding. The results suggest that the two mutants have
      compromised catalysis for two different reasons. In D1393V nNOSr, hydride
      transfer from NADPH to FAD is so slow that it compromises all downstream electron
      transfer events. In D1393N nNOSr, the increased oxidation of reduced flavins by
      O(2) and thermodynamic destabilization of the FAD semiquinone uncouples or limits
      electron transfer to an extent that it inhibits downstream catalysis. These
      effects are due in part to the mutations eliminating (D1393V) or altering
      (D1393N) the native side-chain hydrogen-bonding properties of Asp(1393) as well
      as removing its negative charge.

PMID- 17029415
TI  - Lactoperoxidase-catalyzed oxidation of thiocyanate by hydrogen peroxide: a
      reinvestigation of hypothiocyanite by nuclear magnetic resonance and optical
      spectroscopy.
AB  - In an effort to reconcile conflicting reports regarding the spectra of the human
      defense factor hypothiocyanite (OSCN(-)), we have synthesized OSCN(-) by three
      methods and characterized the product spectroscopically. Method I is
      lactoperoxidase-catalyzed oxidation of SCN(-) by H(2)O(2) at pH 7. Method II is
      hydrolysis of (SCN)(2) at pH 13. Method III is oxidation of SCN(-) by OX(-) (X =
      Cl and Br) at pH 13. All three methods produced essentially the same initial UV,
      (13)C NMR, and (15)N NMR spectra. The UV spectrum reveals a lambda(max) of 376
      nm, which is a previously unreported distinguishing feature. The (13)C NMR
      spectrum (delta = 127.8 ppm at pH 13 vs dioxane at 66.6 ppm) is comparable to
      those that have been previously reported for OSCN(-) as prepared by methods I and
      II (although in some cases different assignments have been made). However, the
      (15)N NMR spectrum we measure (delta = -80.6 ppm at pH 13 vs NO(3)(-) at 0 ppm)
      contrasts with previous reports. We conclude that all three methods produce the
      same species, and the spectra are now self-consistent with the formulation OSCN(
      ).

PMID- 17029417
TI  - Ceramide drives cholesterol out of the ordered lipid bilayer phase into the
      crystal phase in 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine/cholesterol/ceramide ternary mixtures.
AB  - The effect of brain ceramide on the maximum solubility of cholesterol in ternary
      mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), cholesterol,
      and ceramide was investigated at 37 degrees C by a cholesterol oxidase (COD)
      reaction rate assay and by optical microscopy. The COD reaction rate assay showed
      a sharp increase in cholesterol chemical potential as the cholesterol mole
      fraction approaches the solubility limit. A decline in the COD reaction rate was
      found after the formation of cholesterol crystals. The maximum solubility of
      brain ceramide in POPC bilayers was determined to be 68 +/- 2 mol % by
      microscopy. We found that ceramide has a much higher affinity for the ordered
      bilayers than cholesterol, and the maximum solubility of cholesterol decreases
      with the increase in ceramide content. More significantly, the displacement of
      cholesterol by ceramide follows a 1:1 relation. At the cholesterol solubility
      limit, adding one more ceramide molecule to the lipid bilayer drives one
      cholesterol out of the bilayer into the cholesterol crystal phase, and
      cholesterol is incapable of displacing ceramide from the bilayer phase. On the
      basis of these findings, a ternary phase diagram of the POPC/cholesterol/ceramide
      mixture was constructed. The behaviors of ceramide and cholesterol can be
      explained by the umbrella model. Both ceramide and cholesterol have small polar
      headgroups and relatively large nonpolar bodies. In a PC bilayer, ceramide and
      cholesterol compete for the coverage of the headgroups of neighboring PC to
      prevent the exposure of their nonpolar bodies to water. This competition results
      in the 1:1 displacement as well as the displacement of cholesterol by ceramide
      from lipid raft domains.

PMID- 17029420
TI  - Theories of reactive scattering.
AB  - This paper is an overview of the theory of reactive scattering, with emphasis on
      fully quantum mechanical theories that have been developed to describe simple
      chemical reactions, especially atom-diatom reactions. We also describe related
      quasiclassical trajectory applications, and in all of this review the emphasis is
      on methods and applications concerned with state-resolved reaction dynamics. The
      review first provides an overview of the development of the theory, including a
      discussion of computational methods based on coupled channel calculations,
      variational methods, and wave packet methods. Choices of coordinates, including
      the use of hyperspherical coordinates are discussed, as are basis set and
      discrete variational representations. The review also summarizes a number of
      applications that have been performed, especially the two most comprehensively
      studied systems, H+H2 and F+H2, along with brief discussions of a large number of
      other systems, including other hydrogen atom transfer reactions, insertion
      reactions, electronically nonadiabatic reactions, and reactions involving four or
      more atoms. For each reaction we describe the method used and important new
      physical insight extracted from the results.

PMID- 17029421
TI  - Infrared studies of ionic clusters: the influence of Yuan T. Lee.
AB  - Beginning in the mid-1980s, a number of innovative experimental studies on ionic
      clusters emerged from the laboratory of Yuan T. Lee combining infrared laser
      spectroscopy and tandem mass spectrometry. Coupled with modern electronic
      structure calculations, this research explored many facets of ionic clusters
      including solvation, structure, and dynamics. These efforts spawned a resurgence
      in gas-phase cluster spectroscopy. This paper will focus on the major areas of
      research initiated by the Lee group and how these studies stimulated and
      influenced others in what is currently a vibrant and growing field.

PMID- 17029416
TI  - Structure/function mapping of amino acids in the N-terminal zinc finger of the
      human immunodeficiency virus type 1 nucleocapsid protein: residues responsible
      for nucleic acid helix destabilizing activity.
AB  - The nucleocapsid protein (NC) of HIV-1 is 55 amino acids in length and possesses
      two CCHC-type zinc fingers. Finger one (N-terminal) contributes significantly
      more to helix destabilizing activity than finger two (C-terminal). Five amino
      acids differ between the two zinc fingers. To determine at the amino acid level
      the reason for the apparent distinction between the fingers, each different
      residue in finger one was incrementally replaced by the one at the corresponding
      location in finger two. Mutants were analyzed in annealing assays with
      unstructured and structured substrates. Three groupings emerged: (1) those
      similar to wild-type levels (N17K, A25M), (2) those with diminished activity
      (I24Q, N27D), and (3) mutant F16W, which had substantially greater helix
      destabilizing activity than that of the wild type. Unlike I24Q and the other
      mutants, N27D was defective in DNA binding. Only I24Q and N27D showed reduced
      strand transfer in in vitro assays. Double and triple mutants F16W/I24Q,
      F16W/N27D, and F16W/I24Q/N27D all showed defects in DNA binding, strand transfer,
      and helix destabilization, suggesting that the I24Q and N27D mutations have a
      dominant negative effect and abolish the positive influence of F16W. Results show
      that amino acid differences at positions 24 and 27 contribute significantly to
      finger one's helix destabilizing activity.

PMID- 17029422
TI  - Probing chemical dynamics with negative ions.
AB  - Experiments are reviewed in which key problems in chemical dynamics are probed by
      experiments based on photodetachment and/or photoexcitation of negative ions.
      Examples include transition state spectroscopy of biomolecular reactions,
      spectroscopy of open shell van der Waals complexes, photodissociation of free
      radicals, and time-resolved dynamics in clusters. The experimental methods used
      in these investigations are described along with representative systems that have
      been studied.

PMID- 17029423
TI  - State-to-state reaction dynamics: a selective review.
AB  - A selective review of state-to-state reaction dynamics experiments is presented.
      The review focuses on three classes of reactions that exemplify the rich history
      and illustrate the current state of the art in such work. These three reactions
      are (1) the hydrogen exchange reaction, H+H2-->H2+H and its isotopomers; (2) the
      H+RH-->H2+R reactions, where RH is an alkane, beginning with H+CH4-->H2+CH3 and
      extending to much larger alkanes; and (3) the Cl+RH-->HCl+R reactions,
      principally Cl+CH4-->HCl+CH3. We describe the experiments, discuss their results,
      present comparisons with theory, and introduce heuristic models.

PMID- 17029424
TI  - Including quantum effects in the dynamics of complex (i.e., large) molecular
      systems.
AB  - The development in the 1950s and 1960s of crossed molecular beam methods for
      studying chemical reactions at the single-collision molecular level stimulated
      the need and desire for theoretical methods to describe these and other dynamical
      processes in molecular systems. Chemical dynamics theory has made great strides
      in the ensuing decades, so that methods are now available for treating the
      quantum dynamics of small molecular systems essentially completely. For the large
      molecular systems that are of so much interest nowadays (e.g., chemical reactions
      in solution, in clusters, in nanostructures, in biological systems, etc.),
      however, the only generally available theoretical approach is classical molecular
      dynamics (MD) simulations. Much effort is currently being devoted to the
      development of approaches for describing the quantum dynamics of these complex
      systems. This paper reviews some of these approaches, especially the use of
      semiclassical approximations for adding quantum effects to classical MD
      simulations, also showing some new versions that should make these semiclassical
      approaches even more practical and accurate.

PMID- 17029425
TI  - The study of state-selected ion-molecule reactions using the vacuum ultraviolet
      pulsed field ionization-photoion technique.
AB  - This paper presents the methodology to generate beams of ions in single quantum
      states for bimolecular ion-molecule reaction dynamics studies using pulsed field
      ionization (PFI) of atoms or molecules in high-n Rydberg states produced by
      vacuum ultraviolet (VUV) synchrotron or laser photoexcitation. Employing the
      pseudocontinuum high-resolution VUV synchrotron radiation at the Advanced Light
      Source as the photoionization source, PFI photoions (PFI-PIs) in selected
      rovibrational states have been generated for ion-molecule reaction studies using
      a fast-ion gate to pass the PFI-PIs at a fixed delay with respect to the
      detection of the PFI photoelectrons (PFI-PEs). The fast ion gate provided by a
      novel interleaved comb wire gate lens is the key for achieving the optimal signal
      to-noise ratio in state-selected ion-molecule collision studies using the VUV
      synchrotron based PFI-PE secondary ion coincidence (PFI-PESICO) method. The most
      recent development of the VUV laser PFI-PI scheme for state-selected ion-molecule
      collision studies is also described. Absolute integral cross sections for state
      selected H2+ ions ranging from v+ = 0 to 17 in collisions with Ar, Ne, and He at
      controlled translational energies have been obtained by employing the VUV
      synchrotron based PFI-PESICO scheme. The comparison between PFI-PESICO cross
      sections for the H2+(HD+)+Ne and H2+(HD+)+He proton-transfer reactions and
      theoretical cross sections based on quasiclassical trajectory (QCT) calculations
      and three-dimensional quantum scattering calculations performed on the most
      recently available ab initio potential energy surfaces is highlighted. In both
      reaction systems, quantum scattering resonances enhance the integral cross
      sections significantly above QCT predictions at low translational and vibrational
      energies. At higher energies, the agreement between experiment and quasiclassical
      theory is very good. The profile and magnitude of the kinetic energy dependence
      of the absolute integral cross sections for the H2+(v+ = 0-2,N+ = 1)+He proton
      transfer reaction unambiguously show that the inclusion of Coriolis coupling is
      important in quantum dynamics scattering calculations of ion-molecule collisions.

PMID- 17029426
TI  - Recent advances in crossed-beam studies of bimolecular reactions.
AB  - A critical overview of the recent progress in crossed-beam reactive scattering is
      presented. This review is not intended to be an exhaustive nor a comprehensive
      one, but rather a critical assessment of what we have been learning about
      bimolecular reaction dynamics using crossed molecular beams since year 2000.
      Particular emphasis is placed on the information content encoded in the product
      angular distribution-the trait of a typical molecular beam scattering experiment
      and how the information can help in answering fundamental questions about
      chemical reactivity. We will start with simple reactions by highlighting a few
      benchmark three-atom reactions, and then move on progressively to the more
      complex chemical systems and with more sophisticated types of measurements.
      Understanding what cause the experimental observations is more than
      computationally simulating the results. The give and take between experiment and
      theory in unraveling the physical picture of the underlying dynamics is
      illustrated throughout this review.

PMID- 17029427
TI  - Mode- and bond-selective reaction of Cl(2P3/2) with CH3D: C-H stretch overtone
      excitation near 6000 cm(-1).
AB  - Experiments explore the influence of different C-H stretching eigenstates of CH3D
      on the reaction of CH3D with Cl(2P3/2). We prepare the mid |110>|0>(A1,E), mid
      |200>|>0(E), and mid |100>|0> +nu3 +nu5 eigenstates by direct midinfrared
      absorption near 6000 cm(-1). The vibrationally excited molecules react with
      photolytic Cl atoms, and we monitor the vibrational states of the CH2D or CH3
      radical products by 2+1 resonance enhanced multiphoton ionization. Initial
      excitation of the |200>|0>(E) state leads to a twofold increase in CH2D products
      in the vibrational ground state compared to|100>|0> +nu3 +nu5 excitation,
      indicating mode-selective chemistry in which the C-H stretch motion couples more
      effectively to the H-atom abstraction coordinate than bend motion. For two
      eigenstates that differ only in the symmetry of the vibrational wave function,
      |110>|0>(A1) and |110>|0>(E), the ratio of reaction cross sections is 1.00 +/-
      0.05, showing that there is no difference in enhancement of the H-atom
      abstraction reaction. Molecules with excited local modes corresponding to one
      quantum of C-H stretch in each of two distinct oscillators react exclusively to
      form C-H stretch excited CH2D products. Conversely, eigenstates containing
      stretch excitation in a single C-H oscillator form predominantly ground
      vibrational state CH2D products. Analyzing the product state yields for reaction
      of the |110>|0>(A1) state of CH3D yields an enhancement of 20 +/- 4 over the
      thermal reaction. A local mode description of the vibrational motion along with a
      spectator model for the reactivity accounts for all of the observed dynamics.

PMID- 17029428
TI  - State-to-state quantum reactive scattering for four-atom chemical reactions:
      differential cross section for the H+H2O-->H2+OH abstraction reaction.
AB  - The time-dependent wave packet method was extended to calculate the state-to
      state differential cross section for the title four-atom abstraction reaction
      with H2O in the ground rovibrational state. One spectator OH bond length was
      fixed in the study, but the remaining five degrees of freedom were treated
      exactly. It was found that (a) the differential cross section changes from being
      strongly backward peaked at low collision energy to sideward scattering at E =
      1.4 eV, and (b) the rotational state-resolved differential cross section for H2
      differs substantially from that for OH.

PMID- 17029429
TI  - A crossed molecular beam study on the dynamics of F atom reaction with SiH4.
AB  - In this report, the dynamics of the F+SiH4 reaction has been studied using the
      universal crossed molecular beam method. Angular resolved time-of-flight spectra
      have been measured for all reaction products in a single set of experiments. Two
      different reaction channels have been observed: HF+SiH3 and SiH3F+H. Product
      angular distributions as well as energy distributions were determined for these
      two product channels. Experimental results show that the HF product is forward
      scattered relative to the F atom beam direction, while the SiH3F product is
      backward scattered relative the F atom beam direction, suggesting that two
      reaction channels proceed with distinctive reaction dynamics. The relative
      branching ratios of the two channels have also been estimated.

PMID- 17029430
TI  - Mechanism and control of the F+H2 reaction at low and ultralow collision
      energies.
AB  - This article uses theoretical methods to study the dependence on stereodynamical
      factors of the mechanism and reactivity of the F+H2 reaction at low and ultralow
      collision energies. The impact of polarization of the H2 reactant on total and
      state-to-state integral and differential cross sections is analyzed. This leads
      to detailed pictures of the reaction mechanism in the cold and ultracold regimes,
      accounting, in particular, for distinctions associated with the various product
      states and scattering angles. The extent to which selection of reactant
      polarization allows for external control of the reactivity and reaction mechanism
      is assessed. This reveals that even the simplest of reactant polarization schemes
      allows for fine, product state-selective control of differential and (for
      reactions involving more than a single, zero orbital angular momentum partial
      wave) integral cross sections.

PMID- 17029431
TI  - Energy transfer between azulene and krypton: comparison between experiment and
      computation.
AB  - Trajectory calculations of collisional energy transfer between excited azulene
      and Kr are reported, and the results are compared with recent crossed molecular
      beam experiments by Liu et al. [J. Chem. Phys. 123, 131102 (2005); 124, 054302
      (2006)]. Average energy transfer quantities are reported and compared with
      results obtained before for azulene-Ar collisions. A collisional energy transfer
      probability density function P(E,E'), calculated at identical initial conditions
      as experiments, shows a peak at the up-collision branch of P(E,E') at low initial
      relative translational energy. This peak is absent at higher relative
      translational energies. There is a supercollision tail at the down-collision side
      of the probability distribution. Various intermolecular potentials are used and
      compared. There is broad agreement between experiment and computation, but there
      are some differences as well.

PMID- 17029432
TI  - A crossed-beam study of the F+HD-->HF+D reaction: the resonance-mediated channel.
AB  - This is the last report of our extensive studies on the title reaction. Presented
      here are the state-to-state differential cross section determinations at 11
      collision energies, ranging from 1.30 to 4.53 kcal/mol. Together with previously
      reported results at six lower energies (0.4-1.18 kcal/mol), this perhaps
      represents one of the most comprehensive set of data from a single investigation
      for any chemical reaction. The information contents of this set of data are
      examined in detail, from which the dynamical consequences of reactive resonances
      are elucidated. Qualitative interpretations of some of the major findings are
      proposed. Observations that need further theoretical investigations for better
      physical understanding are pointed out.

PMID- 17029433
TI  - Rotationally resolved reactive scattering: imaging detailed Cl+C2H6 reaction
      dynamics.
AB  - The hydrogen atom abstraction reaction of Cl (2P3/2) with ethane has been studied
      using the crossed molecular beam technique with dc slice imaging at collision
      energies from 3.2 to 10.4 kcal/mol. The products HCl (v,J) (v = 0, J = 0-5) were
      state-selectively detected using 2+1 resonance enhanced multiphoton ionization.
      The images were used to obtain the center-of-mass frame product angular
      distributions and translational energy release distributions. Two general
      features were found in all probed HCl quantum states at 6.7 kcal/mol collision
      energy, and these features have distinct translational energy release and angular
      distributions, as described for HCl (v = 0, J = 2) in a recent preliminary report
      [Li et al., J. Chem. Phys. 124, 011102 (2006)]. The results for HCl (v = 0, J =
      2) at four collision energies were also compared to investigate the energy
      dependent dynamics. We discuss the reaction in terms of a variety of models of
      polyatomic reaction dynamics. The dynamics of this well studied system are more
      complicated than can be accounted for by a single mechanism, and the results call
      for further theoretical and experimental investigations.

PMID- 17029434
TI  - Nonadiabatic effects in the H+D2 reaction.
AB  - The state-to-state dynamics of the H+D2 reaction is studied by the reactant
      product decoupling method using the double many-body expansion potential energy
      surface. Two approaches are compared: one uses only the lowest adiabatic sheet
      while the other employs both coupled diabatic sheets. Rotational distributions
      for the reaction H+D2 (upsilon = 0, j = 0)-->HD(upsilon' = 3, j')+D are obtained
      at eight different collision energies between 1.49 and 1.85 eV; no significant
      difference are found between the two approaches. Initial state-selected total
      reaction probabilities and integral cross sections are also given for energies
      ranging from 0.25 up to 2.0 eV with extremely small differences being observed
      between the two sets of results, thus showing that the nonadiabatic effects in
      the title reaction are negligible at least for small energies below 2.0 eV.

PMID- 17029435
TI  - Exact quantum calculations of the kinetic isotope effect: cross sections and rate
      constants for the F+HD reaction and role of tunneling.
AB  - In this paper we present integral cross sections (in the 5-220 meV collision
      energy range) and rate constants (in the 100-300 K range of temperature) for the
      F+HD reaction leading to HF+D and DF+H. The exact quantum reactive scattering
      calculations were carried out using the hyperquantization algorithm on an
      improved potential energy surface which incorporates the effects of open shell
      and fine structure of the fluorine atom in the entrance channel. The results
      reproduce satisfactorily molecular beam scattering experiments as well as
      chemical kinetics data for both the HF and DF channels. In particular, the
      agreement of the rate coefficients and the vibrational branching ratios with
      experimental measurements is improved with respect to previous studies. At
      thermal and subthermal energies, the rates are greatly influenced by tunneling
      through the reaction barrier. Therefore exchange of deuterium is shown to be
      penalized with respect to exchange of hydrogen, and the isotopic branching
      exhibits a strong dependence on translational energy. Also, it is found that
      rotational excitation of the reactant HD molecule enhances the production of HF
      and decreases the reactivity at the D end, obtaining insight on the reaction
      stereodynamics.

PMID- 17029436
TI  - Inelastic scattering from glyoxal: collision kinematics rather than the
      interaction potential dominates rotational channel selection.
AB  - Relative cross sections have been obtained for the rotationally and
      rovibrationally inelastic scattering of S1 trans-glyoxal (CHO-CHO) in its zero
      point level with K' = 0 from the target gases H2, D2, and He. Emphasis is placed
      on using crossed molecular beam conditions that provide several choices of
      collision kinematics (center-of-mass collision energy, relative velocity, center
      of-mass collision momentum) for each collision pair. The cross sections define
      the state-to-state competition among numerous rotational channels involving
      destination states with DeltaK' ranging from 1 to >15 for collisions with each
      target gas and under every kinematic condition. They also resolve a similar
      rotational competition among rovibrational channels where the torsion nu7' is
      collisionally excited. The cross section sets also allow the relative overall
      magnitudes of the two types of scattering to be compared. The primary motivation
      of these experiments concerns the rotationally inelastic scattering. Earlier
      studies with rare gases and fixed kinematics demonstrated that the distribution
      of rotational cross sections is remarkably similar from one collision pair to
      another. The new data show that the competition among rotational channels
      actually has a small but distinct dependence on kinematic conditions. Data
      analysis shows that the dependence is a systematic function of the available
      collision momentum and entirely unrelated to the identity of the target gases,
      including the heavier rare gases used in earlier studies. The competition among
      the rotational energy transfer channels and its kinematic heritage is discussed
      in the context of a classical hard ellipse model of linear momentum to angular
      momentum conversion much used with room temperature systems. When adapted to our
      beam conditions, the resulting account of the rotational scattering is accurate
      and provides insight into the collisional details.

PMID- 17029437
TI  - Intermolecular interactions of H2S with rare gases from molecular beam scattering
      in the glory regime and from ab initio calculations.
AB  - Integral cross sections for collisions of rotationally hot H2S molecules with
      rare gas atoms (Ne, Ar, and Kr) have been measured, in the collision energy range
      of 10-60 kJ mol(-1), using a molecular beam apparatus operating under high
      resolution both in angle and in velocity. A well resolved glory pattern has been
      measured which permitted the accurate characterization of the intermolecular
      potentials both at long range (in the attractive region) and at intermediate
      distances (in the well region). Considering the conditions used in the
      experiments, the obtained potentials must be considered very close to the
      spherical averages of the full intermolecular potential energy surfaces.
      Extensive ab initio calculations have also been carried out in parallel in order
      to characterize energy minima in the potential energy surfaces and energy
      barriers associated to the motion of the rare gas atoms around H2S. An assessment
      of the relative role of the various interaction components has been also
      attempted: the combined analysis of experimental and theoretical results suggests
      that H2S-rare gas aggregates are mainly bound by nearly isotropic noncovalent
      interactions of the van der Waals type.

PMID- 17029438
TI  - Parity-dependent rotational rainbows in D2-NO and He-NO differential collision
      cross sections.
AB  - The (j', Omega', epsilon') dependent differential collision cross sections of D2
      with fully state selected (j = 12, Omega = 12, epsilon = -1) NO have been
      determined at a collision energy of about 550 cm(-1). The collisionally excited
      NO molecules are detected by (1+1') resonance enhanced multiphoton ionization
      combined using velocity-mapped ion-imaging. The results are compared to He-NO
      scattering results and tend to be more forward scattered for the same final
      rotational state. Both for collisions of the atomic He and the molecular D2 with
      NO, scattering into pairs of rotational states with the same value of n = j' -
      epsilon epsilon'2 yields the same angular dependence of the cross section. This
      "parity propensity rule" remains present both for spin-orbit conserving and spin
      orbit changing transitions. The maxima in the differential cross sections-that
      reflect rotational rainbows-have been extracted from the D2-NO and the He-NO
      differential cross sections. These maxima are found to be distinct for odd and
      even parity pair number n. Rainbow positions of parity changing transitions (n is
      odd) occur at larger scattering angles than those of parity conserving
      transitions (n is even). Parity conserving transitions exhibit-from a classical
      point of view-a larger effective eccentricity of the shell. No rainbow doubling
      due to collisions onto either the N-end or the O-end was observed. From a
      classical point of view the presence of a double rainbow is expected. Rotational
      excitation of the D2 molecules has not been observed.

PMID- 17029439
TI  - Ab initio/Rice-Ramsperger-Kassel-Marcus study of the singlet C4H4 potential
      energy surface and of the reactions of C2(X1 Sigmag+) with C4H4(X1A1g) and C(1D)
      with C3H4 (allene and methylacetylene).
AB  - Ab initio modified Gaussian-2 G2M(RCC,MP2) calculations have been performed for
      various isomers and transition states on the singlet C4H4 potential energy
      surface. The computed relative energies and molecular parameters have then been
      used to calculate energy-dependent rate constants for different isomerization and
      dissociation processes in the C4H4 system employing Rice-Ramsperger-Kassel-Marcus
      theory and to predict branching ratios of possible products of the
      C2(1Sigmag+)+C2H4, C(1D)+H2CCCH2, and C(1D)+H3CCCH reactions under single
      collision conditions. The results show that C2 adds to the double C=C bond of
      ethylene without a barrier to form carbenecyclopropane, which then isomerizes to
      butatriene by a formal C2 "insertion" into the C-C bond of the C2H4 fragment.
      Butatriene can rearrange to the other isomers of C4H4, including allenylcarbene,
      methylenecyclopropene, vinylacetylene, methylpropargylene, cyclobutadiene,
      tetrahedrane, methylcyclopropenylidene, and bicyclobutene. The major
      decomposition products of the chemically activated C4H4 molecule formed in the
      C2(1Sigmag+)+C2H4 reaction are calculated to be acetylene+vinylidene (48.6% at
      Ecol = 0) and 1-buten-3-yne-2-yl radical [i-C4H3(X2A'), H2C=C=C=CH*]+H (41.3%).
      As the collision energy increases from 0 to 10 kcal/mol, the relative yield of i
      C4H3+H grows to 52.6% and that of C2H2+CCH2 decreases to 35.5%. For the
      C(1D)+allene reaction, the most important products are also i-C4H3+H (55.2%) and
      C2H2+CCH2 (30.1%), but for C(1D)+methylacetylene, which accesses a different
      region of the C4H4 singlet potential energy surface, the calculated product
      branching ratios differ significantly: 65%-69% for i-C4H3+H, 18%-14% for
      C2H2+CCH2, and approximately 8% for diacetylene+H2.

PMID- 17029440
TI  - Activation of methane by gold cations: guided ion beam and theoretical studies.
AB  - The potential energy surface for activation of methane by the third-row
      transition metal cation, Au+, is studied experimentally by examining the kinetic
      energy dependence of this reaction using guided ion beam tandem mass
      spectrometry. A flow tube ion source produces Au+ primarily in its 1S0 (5d10)
      electronic ground state level but with some 3D (and perhaps higher lying) excited
      states that can be completely removed by a suitable quenching gas (N2O). Au+
      (1S0) reacts with methane by endothermic dehydrogenation to form AuCH2+ as well
      as C-H bond cleavage to yield AuH+ and AuCH3+. The kinetic energy dependences of
      the cross sections for these endothermic reactions are analyzed to give 0 K bond
      dissociation energies (in eV) of D0(Au+ - CH2) = 3.70 +/- 0.07 and D0(Au+ -CH3) =
      2.17 +/- 0.24. Ab initio calculations at the B3LYPHW + /6-311++G(3df,3p) level
      performed here show good agreement with the experimental bond energies and
      previous theoretical values available. Theory also provides the electronic
      structures of the product species as well as intermediates and transition states
      along the reactive potential energy surface. Surprisingly, the dehydrogenation
      reaction does not appear to involve an oxidative addition mechanism. We also
      compare this third-row transition metal system with the first-row and second-row
      congeners, Cu+ and Ag+. Differences in thermochemistry can be explained by the
      lanthanide contraction and relativistic effects that alter the relative size of
      the valence s and d orbitals.

PMID- 17029441
TI  - The effects of collision energy, vibrational mode, and vibrational angular
      momentum on energy transfer and dissociation in NO2+-rare gas collisions: an
      experimental and trajectory study.
AB  - A combined experimental and trajectory study of vibrationally state-selected NO2+
      collisions with Ne, Ar, Kr, and Xe is presented. Ne, Ar, and Kr are similar in
      that only dissociation to the excited singlet oxygen channel is observed;
      however, the appearance energies vary by approximately 4 eV between the three
      rare gases, and the variation is nonmonotonic in rare gas mass. Xe behaves quite
      differently, allowing efficient access to the ground triplet state dissociation
      channel. For all four rare gases there are strong effects of NO2+ vibrational
      excitation that extend over the entire collision energy range, implying that
      vibration influences the efficiency of collision to internal energy conversion.
      Bending excitation is more efficient than stretching; however, bending angular
      momentum partially counters the enhancement. Direct dynamics trajectories for
      NO2+ + Kr reproduce both the collision energy and vibrational state effects
      observed experimentally and reveal that intracomplex charge transfer is critical
      for the efficient energy transfer needed to drive dissociation. The strong
      vibrational effects can be rationalized in terms of bending, and to a lesser
      extent, stretching distortion enhancing transition to the Kr+ -NO2 charge state.

PMID- 17029442
TI  - Direct observation and reactions of Cl3 radical.
AB  - The broad absorption of Cl3 radical was observed between 1150 and 1350 nm using
      cavity ring-down spectroscopy at 213-265 K and 50-200 Torr with He, N2, Ar, or
      SF6 diluents. The absorption intensity of Cl3 increased at lower temperature and
      higher pressure. SF6 was the most efficient diluent gas. The temperature
      dependent equilibrium constants for Cl3 formation from Cl+Cl2 were theoretically
      calculated at the MP4SDQ6-311+G(d) level. Observed decay time profiles of Cl3 and
      the pressure dependence of Cl3 formation are explained by the equilibrium
      reaction and a decay reaction of Cl+Cl3.

PMID- 17029443
TI  - Reaction dynamics of OH+(3Sigma-)+C2H2 studied with crossed beams and density
      functional theory calculations.
AB  - The reactions between OH+(3Sigma-) and C2H2 have been studied using crossed ion
      and molecular beams and density functional theory calculations. Both charge
      transfer and proton transfer channels are observed. Products formed by carbon
      carbon bond cleavage analogous to those formed in the isoelectronic O(3P)+C2H2
      reaction, e.g., 3CH2 + HCO+, are not observed. The center of mass flux
      distributions of both product ions at three different energies are highly
      asymmetric, with maxima close to the velocity and direction of the precursor
      acetylene beam, characteristic of direct reactions. The internal energy
      distributions of the charge transfer products are independent of collision energy
      and are peaked at the reaction exothermicity, inconsistent with either the
      existence of favorable Franck-Condon factors or energy resonance. In proton
      transfer, almost the entire reaction exothermicity is transformed into product
      internal excitation, consistent with mixed energy release in which the proton is
      transferred with both the breaking and forming bonds extended. Most of the
      incremental translational energy in the two higher-energy experiments appears in
      product translational energy, providing an example of induced repulsive energy
      release.

PMID- 17029444
TI  - Dynamics of ionization of H2 by Ne*(3P) investigated by electron spectroscopy.
AB  - The Penning ionization reaction Ne*(2p(5)3s 3P)+H2-->[NeH2]+ +e- has been studied
      in crossed supersonic molecular beams with electron-energy analysis at four
      collision energies E = 1.83, 2.50, 3.16, and 3.89 kcal/mol. The electron kinetic
      energy spectra, which directly reflect the ionizing transition region, show
      resolved peaks assignable to v' = 0-4 of H2+. The vibrational populations deviate
      systematically from Franck-Condon behavior, suggesting that the discrete
      continuum coupling increases with H2 bond stretching. Each peak displays both
      increasing breadth and increasing blueshift with increasing E, and the blueshift
      also increases with increasing v'. The first two properties are consistent with a
      predominantly repulsive excited-state potential-energy surface, while the last is
      speculated to be a reflection of the rHH dependence of the ionic surface. Quantum
      scattering calculations based on ab initio potential surfaces for the excited and
      ionic states in spherical and infinite-order-sudden rigid rotor approximations
      are in semiquantitative agreement with the measurements. Discrepancies suggest
      changes in the imaginary, absorptive part of the excited surface, which probably
      can be best effected by multiproperty fitting calculations.

PMID- 17029445
TI  - Direct ab initio molecular dynamics study on a microsolvated SN2 reaction of OH
      (H2O) with CH3Cl.
AB  - Reaction dynamics for a microsolvated SN2 reaction OH-(H2O)+CH3Cl have been
      investigated by means of the direct ab initio molecular dynamics method. The
      relative center-of-mass collision energies were chosen as 10, 15, and 25
      kcal/mol. Three reaction channels were found as products. These are (1) a channel
      leading to complete dissociation (the products are CH3OH+Cl- +H2O: denoted by
      channel I), (2) a solvation channel (the products are Cl-(H2O)+CH3OH: channel
      II), and (3) a complex formation channel (the products are CH3OH...H2O+Cl-:
      channel III). The branching ratios for the three channels were drastically
      changed as a function of center-of-mass collision energy. The ratio of complete
      dissociation channel (channel I) increased with increasing collision energy,
      whereas that of channel III decreased. The solvation channel (channel II) was
      minor at all collision energies. The selectivity of the reaction channels and the
      mechanism are discussed on the basis of the theoretical results.

PMID- 17029446
TI  - Quasiclassical trajectory study of the reaction H+CH4(nu3 = 0,1)-->CH3+H2 using a
      new ab initio potential energy surface.
AB  - Detailed quasiclassical trajectory calculations of the reaction H+CH4(nu3 = 0,1)-
      >CH3 + H2 using a slightly updated version of a recent ab initio-based CH5
      potential energy surface [X. Zhang et al., J. Chem. Phys. 124, 021104 (2006)] are
      reported. The reaction cross sections are calculated at initial relative
      translational energies of 1.52, 1.85, and 2.20 eV in order to make direct
      comparison with experiment. The relative reaction cross section enhancement ratio
      due to the excitation of the C-H antisymmetric stretch varies from 2.2 to 3.0
      over this energy range, in good agreement with the experimental result of 3.0 +/-
      1.5 [J. P. Camden et al., J. Chem. Phys. 123, 134301 (2005)]. The laboratory
      frame speed and center-of-mass angular distributions of CH3 are calculated as are
      the vibrational and rotational distributions of H2 and CH3. We confirm that this
      reaction occurs with a combination of stripping and rebound mechanisms by
      presenting the impact parameter dependence of these distributions and also by
      direct examination of trajectories.

PMID- 17029447
TI  - Crossed molecular beam studies on the reaction dynamics of O(1D)+N2O.
AB  - The reaction of oxygen atom in its first singlet excited state with nitrous oxide
      was investigated under the crossed molecular beam condition. This reaction has
      two major product channels, NO+NO and N2+O2. The product translational energy
      distributions and angular distributions of both channels were determined. Using
      oxygen-18 isotope labeled O(1D) reactant, the newly formed NO can be
      distinguished from the remaining NO that was contained in the reactant N2O. Both
      channels have asymmetric and forward-biased angular distributions, suggesting
      that there is no long-lived collision complex with lifetime longer than its
      rotational period. The translational energy release of the N2+O2 channel (fT =
      0.57) is much higher than that of the NO+NO channel (fT = 0.31). The product
      energy partitioning into translational, rotational, and vibrational degrees of
      freedom is discussed to learn more about the reaction mechanism. The branching
      ratio between the two product channels was estimated. The 46N2O product of the
      isotope exchange channel, 18O+44N2O-->16O+46N2O, was below the detection limit
      and therefore, the upper limit of its yield was estimated to be 0.8%.

PMID- 17029448
TI  - The bending vibrational levels of the acetylene cation: a case study of the
      Renner-Teller effect in a molecule with two degenerate bending vibrations.
AB  - Forty three vibronic levels of C2H2+, X 2Pi u, with upsilon4 = 0-6, upsilon5 = 0
      3, and K = 0-4, lying at energies of 0-3520 cm(-1) above the zero-point level,
      have been recorded at rotational resolution. These levels were observed by double
      resonance, using 1+1' two-color pulsed-field ionization zero-kinetic-energy
      photoelectron spectroscopy. The intermediate states were single rovibrational
      levels chosen from the A1Au, 4nu3 (K = 1-2), 5nu3 (K = 1), nu2+4nu3 (K = 0), and
      47,206 cm(-1) (K = 1) levels of C2H2. Seven of the trans-bending levels of C2H2+
      (upsilon4 = 0-3, K = 0-2) had been reported previously by Pratt et al. [J. Chem.
      Phys. 99, 6233 (1993)]; our results for these levels agree well with theirs. A
      full analysis has been carried out, including the Renner-Teller effect and the
      vibrational anharmonicity for both the trans- and cis-bending vibrations. The
      rotational structure of the lowest 16 vibronic levels (consisting of the complete
      set of levels with upsilon4 + upsilon5 < or = 2, except for the unobserved upper
      (2Pi u component of the 2nu4 overtone) could be fitted by least squares using 16
      parameters to give an rms deviation of 0.21 cm(-1). The vibronic coupling
      parameter epsilon5 (about whose magnitude there has been controversy) was
      determined to be -0.0273(7). For the higher vibronic levels, an additional
      parameter, r45, was needed to allow for the Darling-Dennison resonance between
      the two bending manifolds. Almost all the observed levels of the upsilon4 +
      upsilon5 = 3 and 4 polyads (about half of the predicted number) could then be
      assigned. In a final fit to 39 vibronic levels with upsilon4 + upsilon5 < or = 5,
      an rms deviation of 0.34 cm(-1) was obtained using 20 parameters. An interesting
      finding is that Hund's spin-coupling cases (a) and (b) both occur in the Sigmau
      components of the nu4 + 2nu5 combination level. The ionization potential of C2H2
      (from the lowest rotational level of the ground state to the lowest rotational
      level of the cation) is found to be 91,953.77 +/- 0.09 cm(-1) (3sigma).

PMID- 17029449
TI  - Probing the electronic structure of UO+ with high-resolution photoelectron
      spectroscopy.
AB  - The pulsed field ionization-zero kinetic energy photoelectron technique has been
      used to observe the low-lying energy levels of UO+. Rotationally resolved spectra
      were recorded for the ground state and the first nine electronically excited
      states. Extensive vibrational progressions were characterized. Omega+ assignments
      were unambiguously determined from the first rotational lines identified in each
      vibronic band. Term energies, vibrational frequencies, and anharmonicity
      constants for low-lying energy levels of UO+ are reported. In addition, accurate
      values for the ionization energies for UO [48,643.8(2) cm(-1)] and U [49,957.6(2)
      cm(-1)] were determined. The pattern of low-lying electronic states for UO+
      indicates that they originate from the U3+(5f3)O2- configuration, where the
      uranium ion-centered interactions between the 5f electrons are significantly
      stronger than interactions with the intramolecular electric field. The latter
      lifts the degeneracy of U3+ ion-core states, but the atomic angular momentum
      quantum numbers remain reasonably well defined.

PMID- 17029450
TI  - An empirical approach to the bond additivity model in quantitative interpretation
      of sum frequency generation vibrational spectra.
AB  - Knowledge of the ratios between different polarizability betai'j'k' tensor
      elements of a chemical group in a molecule is crucial for quantitative
      interpretation and polarization analysis of its sum frequency generation
      vibrational spectroscopy (SFG-VS) spectrum at interface. The bond additivity
      model (BAM) or the hyperpolarizability derivative model along with experimentally
      obtained Raman depolarization ratios has been widely used to obtain such tensor
      ratios for the CH3, CH2, and CH groups. Successfully, such treatment can
      quantitatively reproduce the intensity polarization dependence in SFG-VS spectra
      for the symmetric (SS) and asymmetric (AS) stretching modes of CH3 and CH2
      groups, respectively. However, the relative intensities between the SS and AS
      modes usually do not agree with each other within this model even for some of the
      simplest molecular systems, such as the air/methanol interface. This fact
      certainly has cast uncertainties on the effectiveness and conclusions based on
      the BAM. One of such examples is that the AS mode of CH3 group has never been
      observed in SFG-VS spectra from the air/methanol interface, while this AS mode is
      usually very strong for SFG-VS spectra from the air/ethanol interface, other
      short chain alcohol, as well as long chain surfactants. In order to answer these
      questions, an empirical approach from known Raman and IR spectra is used to make
      corrections to the BAM. With the corrected ratios between the betai'j'k' tensor
      elements of the SS and AS modes, all features in the SFG-VS spectra of the
      air/methanol and air/ethanol interfaces can be quantitatively interpreted. This
      empirical approach not only provides new understandings of the effectiveness and
      limitations of the bond additivity model but also provides a practical way for
      its application in SFG-VS studies of molecular interfaces.

PMID- 17029451
TI  - Gold as hydrogen: structural and electronic properties and chemical bonding in
      Si3Au3(+0-) and comparisons to Si3H3(+0-).
AB  - A single Au atom has been shown to behave like H in its bonding to Si in several
      mono- and disilicon gold clusters. In the current work, we investigate the AuH
      analogy in trisilicon gold clusters, Si3Au3(+0-). Photoelectron spectroscopy and
      density functional calculations are combined to examine the geometric and
      electronic structure of Si3Au3-. We find that there are three isomers competing
      for the ground state of Si3Au3- as is the case for Si3H3-. Extensive structural
      searches show that the potential energy surfaces of the trisilicon gold clusters
      (Si3Au3-, Si3Au3, and Si3Au3+) are similar to those of the corresponding silicon
      hydrides. The lowest energy isomers for Si3Au3- and Si3Au3 are structurally
      similar to a Si3Au four-membered ring serving as a common structural motif. For
      Si3Au3+, the 2pi aromatic cyclotrisilenylium auride ion, analogous to the
      aromatic cyclotrisilenylium ion (Si3H3+), is the most stable species. Comparison
      of the structures and chemical bonding between Si3Au3(+0-) and the corresponding
      silicon hydrides further extends the isolobal analogy between Au and H.

PMID- 17029452
TI  - Decay dynamics of the long-range H1Sigmag+ state of D2 and H2: experiment and
      theory.
AB  - We present accurate experimental measurements of the lifetimes of rovibrational
      levels of the long-range H1Sigmag+ state for both D2 and H2, obtained directly
      from the observation of the time-dependent decay of the fluorescence from these
      excited levels. These results improve upon and extend those of Reinhold et al.
      [J. Chem. Phys. 112, 10754 (2000)]. Several decay pathways are open to these
      levels including fluorescence, predissociation, and autoionization. We present
      theoretical results for each of these processes, each calculated using the
      simplest but still appropriate level of theory. In particular, the theoretical
      calculations provide a quantitative explanation of the dramatic vibrational
      dependence of the observed lifetimes, the isotope dependence of the lifetimes for
      levels well localized within the H potential well and therefore not subject to
      significant tunneling, and an insight into the role of enhanced tunneling in
      autoionization. In these calculations each of the rovibrational levels of the H
      state is treated individually, without having to engage in a global coupled-state
      calculation.

PMID- 17029453
TI  - The calculated infrared spectrum of Cl-H2O using a new full dimensional ab initio
      potential surface and dipole moment surface.
AB  - We report a full dimensional, ab initio-based global potential energy surface
      (PES) and dipole moment surface for Cl-H2O. Both surfaces are symmetric with
      respect to interchange of the H atoms. The PES is a fit to thousands of
      electronic energies calculated using the coupled-cluster method [CCSD(T)] with a
      moderately large basis (aug-cc-pVTZ). Vibrational energies and wave functions are
      accurately obtained using MULTIMODE. The wave function and dipole moment surface
      are used to calculate and analyze the pure infrared spectrum at 0 K which is
      compared with experiment. Vibrational energies and the infrared spectra for DOD
      and HOD/DOH are also presented.

PMID- 17029454
TI  - Vibrationally mediated photodissociation of ethene isotopic variants preexcited
      to the fourth C-H stretch overtone.
AB  - H and D photofragments produced via vibrationally mediated photodissociation of
      jet-cooled normal ethene (C2H4), 1,2-trans-d2-ethene (HDCCDH), and 1,1-d2-ethene
      (CH2CD2), initially excited to the fourth C-H stretch overtone region, were
      studied for the first time. H and D vibrational action spectra and Doppler
      profiles were measured. The action spectra include partially resolved features
      due to rotational cooling, while the monitored room temperature photoacoustic
      spectra exhibit only a very broad feature in each species. Simulation of the
      spectral contours allowed determination of the band types and origins, limited
      precision rotational constants, and linewidths, providing time scales for energy
      redistribution. The H and D Doppler profiles correspond to low average
      translational energies and show slight preferential C-H over C-D bond cleavage in
      the deuterated variants. The propensities toward H photofragments emerge even
      though the energy flow out of the initially prepared C-H stretch is on a
      picosecond time scale and the photodissociation occurs following internal
      conversion, indicating a more effective release of the light H atoms.

PMID- 17029455
TI  - Collision-free photochemistry of methylazide: observation of unimolecular
      decomposition of singlet methylnitrene.
AB  - Methylazide photolysis at 248 nm has been investigated by ionizing photofragments
      with synchrotron radiation in a photofragmentation translational spectroscopy
      study. CH3N and N2 were the only observed primary products. The translational
      energy release suggests a simple bond rupture mechanism forming singlet
      methylnitrene, 1CH3N, and N2. Thus, these experiments reveal the unimolecular
      decomposition of this highly unstable species. We explain our observations
      through a mechanism which is initiated by the isomerization of 1CH3N to a highly
      internally excited methanimine H2C=NH isomer, which decomposes by 1,1-H2
      elimination forming HNC+H2 as well as sequential H-atom loss (N-H followed by C-H
      bond cleavage), to form HCN. No evidence for dynamics on the triplet manifold of
      surfaces is found.

PMID- 17029456
TI  - Ultraviolet photodissociation of the van der Waals dimer (CH3I)2 revisited. II.
      Pathways giving rise to neutral molecular iodine.
AB  - The formation of neutral I2 by the photodissociation of the methyl iodide dimer,
      (CH3I)2, excited within the A band at 249.5 nm is evaluated using velocity map
      imaging. In previous work [J. Chem. Phys. 122, 204301 (2005)], we showed that the
      formation of I2+ from photodissociation of the methyl iodide dimer takes place
      via ionic channels (through the formation of (CH3I)2+). It is thus not possible
      to detect neutral I2 by monitoring I2+. Neutral I2 is detected in this study by
      monitoring I atoms arising from the photodissociation of I2. Iodine atoms from I2
      photodissociation have a characteristic kinetic energy and angular anisotropy,
      which is registered using velocity map imaging. We use a two-color probe scheme
      involving the photodissociation of nascent I2 at 499 nm, which gives rise to I
      atoms that are ionized by (2+1) resonance enhanced multiphoton ionization at
      304.67 nm. Our estimate of the yield of nascent I2 is based on the comparison
      with the signal from I2 at a known concentration. Using molecular beams with a
      small fraction of CH3I (1% in the expanded mixture) where smaller clusters should
      prevail, the production of I2 was found to be negligible. An upper estimate for
      the quantum yield of I2 from (CH3I)2 dimers was found to be less than 0.4%.
      Experiments with a higher fraction of CH3I (4% in the expanded mixture), which
      favor the formation of larger clusters, revealed an observable formation of I2,
      with an estimated translational temperature of about 820 K. We suggest that this
      observed I2 signal arises from the photodissociation of several CH3I molecules in
      the larger cluster by the same UV pulse, followed by recombination of two nascent
      iodine atoms is responsible for neutral I2 production.

PMID- 17029457
TI  - Rovibrationally selected and resolved state-to-state photoionization of ethylene
      using the infrared-vacuum ultraviolet pulsed field ionization-photoelectron
      method.
AB  - By preparing ethylene [C2H4(X1Ag)] in selected rotational levels of the
      nu11(b1u), nu2+nu12(b1u), or nu9(b2u) vibrational state with infrared (IR) laser
      photoexcitation prior to vacuum ultraviolet (VUV) laser photoionization, we have
      recorded rotationally resolved pulsed field ionization-photoelectron (PFI-PE)
      spectra for C2H4+(X2B3u) in the energy region of 0-3000 cm(-1) above the
      ionization energy (IE) of C2H4(X1Ag). Here, nu2(ag), nu9(b2u), nu11(b1u), and
      nu12(b1u) represent the C-C stretching, CH2 stretching, CH2 stretching, and CH2
      bending modes of C2H4(X1Ag), respectively. The fully rovibrationally resolved
      spectra have allowed unambiguous symmetry assignments of the observed vibrational
      bands, which in turn have provided valuable information on the photoionization
      dynamics of C2H4. The IR-VUV photoionization of C2H4(X1Ag) via the nu11(b1u) or
      nu2+nu12(b1u) vibrational states is found to predominantly produce vibrational
      states of C2H4+(X2B3u) with b1u symmetry, which cannot be observed in single
      photon VUV-PFI-PE measurements of C2H4(X1Ag). The analysis of the observed IR-VUV
      PFI-PE bands has provided the IE(C2H4) = 84,790.2(2) cm(-1) and accurate
      vibrational frequencies for the nu4+(au)[84.1(2) cm(-1)], nu12+(b1u)[1411.7(2)
      cm(-1)], nu4+ +nu12+(b1g)[1482.5(2) cm(-1)], nu2+(ag)[1488.3(2) cm(-1)], nu2+ +
      nu4+(au)[1559.2(2) cm(-1)], 2nu4+ + nu12 +(b1u)[1848.5(2) cm(-1)], 4nu4+ + nu12
      +(b1u)[2558.8(2) cm(-1)], nu2+ + nu12 +(b1u)[2872.7(2) cm(-1)], and
      nu11+(b1u)[2978.7(2) cm(-1)] vibrational states of C2H4+(X2B3u), where nu4+ is
      the ion torsional state. The IE(C2H4) and the nu4+(au), nu2+(ag), and nu2+ + nu4+
      (au) frequencies are in excellent accord with those obtained in previous single
      photon VUV-PFI-PE measurements. The other ion vibrational frequencies represent
      new experimental determinations. We have also performed high-level ab initio
      anharmonic vibrational frequency calculations for C2H4(X1Ag) and C2H4+(X2B3u) at
      the CCSD(T)/aug-cc-pVQZ level for guidance in the assignment of the IR-VUV-PFI-PE
      spectra. All theoretical vibrational frequencies for the neutral and ion, except
      the ion torsional frequency, are found to agree with experimental vibrational
      frequencies to better than 1%.

PMID- 17029458
TI  - Photodissociation and photoisomerization of alpha-fluorotoluene and 4
      fluorotoluene in a molecular beam.
AB  - The photodissociation of jet-cooled alpha-fluorotoluene and 4-fluorotoluene at
      193 and 248 nm was studied using vacuum ultraviolet (vuv)
      photoionization/multimass ion imaging techniques as well as electron impact
      ionization/photofragment translational spectroscopy. Four dissociation channels
      were observed for alpha-fluorotoluene at both 193 and 248 nm, including two major
      channels C6H5CH2F-->C6H5CH2 (or C7H7)+F and C6H5CH2F-->C6H5CH (or C7H6)+HF and
      two minor channels C6H5CH2F-->C6H5CHF+H and C6H5CH2F-->C6H5+CH2F. The vuv
      wavelength dependence of the C7H7 fragment photoionization spectra indicates that
      at least part of the F atom elimination channel results from the isomerization of
      alpha-fluorotoluene to a seven-membered ring prior to dissociation. Dissociation
      channels of 4-fluorotoluene at 193 nm include two major channels C6H4FCH3-
      >C6H4FCH2+H and C6H4FCH3-->C6H4F+CH3 and two minor channels C6H4FCH3-->C6H5CH2
      (or C7H7)+F and C6H4FCH3-->C6H5CH (or C7H6)+HF. The dissociation rates for alpha
      fluorotoluene at 193 and 248 nm are 3.3 x 10(7) and 5.6 x 10(5) s(-1),
      respectively. The dissociation rate for 4-fluorotoluene at 193 nm is 1.0 x 10(6)
      s(-1). An ab initio calculation demonstrates that the barrier height for
      isomerization from alpha-fluorotoluene to a seven-membered ring isomer is much
      lower than that from 4-fluorotoluene to a seven-membered ring isomer. The
      experimental observed differences of dissociation rates and relative branching
      ratios between alpha-fluorotoluene and 4-fluorotoluene may be explained by the
      differences in the six-membered ring to seven-membered ring isomerization barrier
      heights, F atom elimination threshold, and HF elimination threshold between alpha
      fluorotoluene and 4-fluorotoluene.

PMID- 17029459
TI  - Unimolecular dissociation of the propargyl radical intermediate of the CH+C2H2
      and C+C2H3 reactions.
AB  - This paper examines the unimolecular dissociation of propargyl (HCCCH2) radicals
      over a range of internal energies to probe the CH+HCCH and C+C2H3 bimolecular
      reactions from the radical intermediate to products. The propargyl radical was
      produced by 157 nm photolysis of propargyl chloride in crossed laser-molecular
      beam scattering experiments. The H-loss and H2 elimination channels of the
      nascent propargyl radicals were observed. Detection of stable propargyl radicals
      gave an experimental determination of 71.5 (+5-10) kcal/mol as the lowest barrier
      to dissociation of the radical. This barrier is significantly lower than
      predictions for the lowest barrier to the radical's dissociation and also lower
      than calculated overall reaction enthalpies. Products from both H2+HCCC and
      H+C3H2 channels were detected at energies lower than what has been theoretically
      predicted. An HCl elimination channel and a minor C-H fission channel were also
      observed in the photolysis of propargyl chloride.

PMID- 17029460
TI  - Spectroscopy and femtosecond dynamics of the ring opening reaction of 1,3
      cyclohexadiene.
AB  - The early stages of the ring opening reaction of 1,3-cyclohexadiene to form its
      isomer 1,3,5-hexatriene, upon excitation to the ultrashort-lived 1 1B2 state,
      were explored. A series of one-color two-photon ionization/photoelectron spectra
      reveal a prominent vibrational progression with a frequency of 1350 cm(-1), which
      is interpreted in a dynamical picture as resulting from the ultrafast wave packet
      dynamics associated with the ring opening reaction. Photoionization in two-color
      three-photon and one-color four-photon ionization schemes show an ionization
      pathway via the same ultrashort-lived 1 1B2 state, and in addition, a series of
      Rydberg states with quantum defects of 0.93, 0.76, and 0.15, respectively. Using
      those Rydberg states as probes for the reaction dynamics in a time-resolved pump
      probe experiment provides a direct observation of the elusive 2 1A1 state that
      has been implicated as an intermediate step between the initially excited 1 1B2
      state and the ground electronic state. The rise and decay times for the 2 1A1
      state were found to be 55 and 84 fs, respectively.

PMID- 17029461
TI  - The photodissociation dynamics of ozone at 193 nm: an O(1D2) angular momentum
      polarization study.
AB  - Polarized laser photolysis, coupled with resonantly enhanced multiphoton
      ionization detection of O(1D2) and velocity-map ion imaging, has been used to
      investigate the photodissociation dynamics of ozone at 193 nm. The use of
      multiple pump and probe laser polarization geometries and probe transitions has
      enabled a comprehensive characterization of the angular momentum polarization of
      the O(1D2) photofragments, in addition to providing high-resolution information
      about their speed and angular distributions. Images obtained at the probe laser
      wavelength of around 205 nm indicate dissociation primarily via the Hartley band,
      involving absorption to, and diabatic dissociation on, the B 1B2(3 1A1) potential
      energy surface. Rather different O(1D2) speed and electronic angular momentum
      spatial distributions are observed at 193 nm, suggesting that the dominant
      excitation at these photon energies is to a state of different symmetry from that
      giving rise to the Hartley band and also indicating the participation of at least
      one other state in the dissociation process. Evidence for a contribution from
      absorption into the tail of the Hartley band at 193 nm is also presented. A
      particularly surprising result is the observation of nonzero, albeit small values
      for all three rank K = 1 orientation moments of the angular momentum
      distribution. The polarization results obtained at 193 and 205 nm, together with
      those observed previously at longer wavelengths, are interpreted using an
      analysis of the long range quadrupole-quadrupole interaction between the O(1D2)
      and O2(1Deltag) species.

PMID- 17029462
TI  - Dissociative photodetachment dynamics of the iodide-aniline cluster.
AB  - The photodetachment dynamics of the iodide-aniline cluster, I-(C6H5NH2), were
      investigated using photoelectron-photofragment coincidence spectroscopy at
      several photon energies between 3.60 and 4.82 eV in concert with density
      functional theory calculations. Direct photodetachment from the solvated I-
      chromophore and a wavelength-independent autodetachment process were observed.
      Autodetachment is attributed to a charge-transfer-to-solvent reaction in which
      incipient continuum electrons photodetached from I- are temporarily captured by
      the nascent neutral iodine-aniline cluster configured in the anion geometry.
      Subsequent dissociation of the neutral cluster removes the stabilization, leading
      to autodetachment of the excess electron. The dependence of the dissociative
      photodetachment (DPD) and autodetachment dynamics on the final spin-orbit
      electronic state of the iodine fragment is characterized. The dissociation
      dynamics of the neutral fragments correlated with autodetached electrons were
      found to be identical to the DPD dynamics of the I atom product spin-orbit state
      closest to threshold at a given photon energy, lending support to the proposed
      sequential mechanism.

PMID- 17029463
TI  - Dissociation of heme from gaseous myoglobin ions studied by infrared multiphoton
      dissociation spectroscopy and Fourier-transform ion cyclotron resonance mass
      spectrometry.
AB  - Detachment of heme prosthetic groups from gaseous myoglobin ions has been studied
      by collision-induced dissociation and infrared multiphoton dissociation in
      combination with Fourier-transform ion cyclotron resonance mass spectrometry.
      Multiply charged holomyoglobin ions (hMbn+) were generated by electrospray
      ionization and transferred to an ion cyclotron resonance cell, where the ions of
      interest were isolated and fragmented by either collision with Ar atoms or
      irradiation with 3 mum photons, producing apomyoglobin ions (aMbn+). Both charged
      heme loss (with [Fe(III)-heme]+ and aMb(n-1)+ as the products) and neutral heme
      loss (with [Fe(II)-heme] and aMbn+ as the products) were detected concurrently
      for hMbn+ produced from a myoglobin solution pretreated with reducing reagents.
      By reference to Ea = 0.9 eV determined by blackbody infrared radiative
      dissociation for charged heme loss of ferric hMbn+, an activation energy of 1.1
      eV was deduced for neutral heme loss of ferrous hMbn+ with n = 9 and 10.

PMID- 17029464
TI  - Photodissociation dynamics of CBr4 at 267 nm by means of ion velocity imaging.
AB  - The photodissociation dynamics of CBr4 at 267 nm has been studied using time of
      flight (TOF) mass spectrometry and ion velocity imaging techniques. The
      photochemical products are detected with resonance enhanced multiphoton
      ionization (REMPI) as well as single-photon vacuum ultraviolet ionization at 118
      nm. REMPI at 266.65 and 266.71 nm was used to detect the ground Br(2P32) and spin
      orbit excited Br(2P12) atoms, respectively. The translational energy and angular
      distributions are consistent with direct dissociation from an excited triplet
      state and indirect dissociation from high vibrational levels on the singlet
      ground state surface. Br2+ ions are also observed in the TOF spectra with a
      focused 267 nm laser. The counter fragment, CBr2+, is observed when this
      photolysis laser is unfocused, and photons at 118 nm are used to ionize the
      radical products. The translational energy distributions of the CBr2+ and Br2+
      products can be momentum matched, which indicates that molecular Br2 elimination
      is one of the primary dissociation channels.

PMID- 17029465
TI  - Photodissociation of nitrous oxide starting from excited bending levels.
AB  - The photodissociation dynamics of N2O in the wavelength region of 203-205 nm was
      studied by velocity map ion imaging. A speed resolution of 0.8% was obtained
      using standard projection imaging and subpixel centroiding calculations. To
      investigate N2O dissociation starting from the excited bending levels in the
      ground electronic state, a supersonic molecular beam and an effusive beam were
      used. The photoabsorption transition probability from the first excited bending
      level in the wavelength region of 203-205 nm was estimated to be seven times
      greater than that from the ground vibrational level.

PMID- 17029466
TI  - Vector properties of the O(1D2) fragment produced from the photolysis of ozone in
      the wavelength range of 298 to 320 nm.
AB  - The speed averaged translational anisotropy and electronic angular momentum
      polarization of the O(1D2) atomic fragment formed from the photodissociation of
      ozone in the atmospherically important long wavelength region of the Hartley band
      (298 to 320 nm) have been measured using resonance enhanced multiphoton
      ionization time of flight mass spectrometry. The translational anisotropy
      parameter, beta, is found to decline from 1.1 for photolysis at 300 nm to a
      minimum value of 0 at 310 nm which is the threshold for production of O(1D2) in
      conjunction with the O2(a 1Deltag v = 0) molecular cofragment. For photolysis
      wavelengths greater than 310 nm, O(1D2) is formed from the dissociation of
      internally excited ozone molecules. The corresponding beta parameters are
      markedly lower than for atomic fragments produced with the same speed from the
      photolysis of ground state ozone molecules. This result is consistent with two
      different pathways contributing to the photolysis of internally excited ozone at
      the longest wavelengths studied corresponding to initial internal excitation
      either in the symmetric or asymmetric stretching vibration. In addition, the
      polarization of the atomic angular momentum has been determined with the
      incoherent polarization parameters a0(2)(||) and a0(2)(_|) increasing from values
      of -0.53 and -0.62 at 300 nm to -0.37 and -0.19 at 317 nm, consistent with the
      increasing contribution from the photolysis of internally excited ozone as the
      dissociation wavelength lengthens. Evaluation of these alignment parameters
      allows the populations of the magnetic substrates, mj, to be determined. For
      example, for a photolysis wavelength of 303 nm the populations of mj = 0, +/- 1,
      +/- 2 are in the ratio of 0.36: 0.56: 0.08 and this ratio is essentially
      independent of the photolysis wavelength. The coherent contribution to the atomic
      polarization is quantified by the Re{a1(2)(||, _|)} and Im{a1(1)(||, _|)}
      parameters and these are found to vary from -0.21 and 0.21 at 300 nm to -0.04 and
      0.24 at 313 nm, respectively.

PMID- 17029467
TI  - Enhanced selectivity and yield in multichannel photodissociation reactions:
      application to CH3I.
AB  - We develop a method to improve the population transfer and final-channel control
      of multichannel photodissociation reactions. The method is applied to the
      photodissociation of methyl iodide, CH3(v)+I*(2P1/2)<--CH3I-->CH3(v)+I(2P3/2).
      Our method is based on simultaneously exciting many two-photon pathways that lead
      to the same final outcome, each proceeding via a different intermediate bound
      state. The selectivity of the final product state(s) is a result of coherently
      controlled interference between the quantum pathways. The improvement in the
      population transfer yield from the ground state to the selected dissociative
      channel(s) is made possible by executing the process in an adiabatic fashion.

PMID- 17029468
TI  - Two-color visible/vacuum ultraviolet photoelectron imaging dynamics of Br2.
AB  - An experimental two-color photoionization dynamics study of laser-excited Br2
      molecules is presented, combining pulsed visible laser excitation and tunable
      vacuum ultraviolet (VUV) synchrotron radiation with photoelectron imaging. The X
      1Sigmag + -B 3Pi0+u transition in Br2 is excited at 527 nm corresponding
      predominantly to excitation of the v' = 28 vibrational level in the B 3Pi0+u
      state. Tunable VUV undulator radiation in the energy range of 8.40-10.15 eV is
      subsequently used to ionize the excited molecules to the X 2Pi32,12 state of the
      ion, and the ionic ground state is probed by photoelectron imaging. Similar
      experiments are performed using single-photon synchrotron ionization in the
      photon energy range of 10.75-12.50 eV without any laser excitation. Photoelectron
      kinetic energy distributions are extracted from the photoelectron images. In the
      case of two-color photoionization using resonant excitation of the intermediate B
      3Pi0+u state, a broad distribution of photoelectron kinetic energies is observed,
      and in some cases even a bimodal distribution, which depends on the VUV photon
      energy. In contrast, for single-photon ionization, a single nearly Gaussian
      shaped distribution is observed, which shifts to higher energy with photon
      energy. Simulated spectra based on Franck-Condon factors for the transitions
      Br2(X 1Sigmag+, v" = 0)-Br2 +(X 2Pi12,32, v+) and Br2(B 3Pi0+u, v' = 28)-Br2 +(X
      2Pi12,32, v+) are generated. Comparison of these calculated spectra with the
      measured images suggests that the differences in the kinetic energy distributions
      for the two ionization processes reflect the different extensions of the
      vibrational wave functions in the v" = 0 electronic ground state (X 1Sigmag+)
      versus the electronically and vibrationally excited state (B 3Pi0+u, v' = 28).

PMID- 17029469
TI  - Anisotropy of photofragment recoil as a function of dissociation lifetime,
      excitation frequency, rotational level, and rotational constant.
AB  - Quantum mechanical calculations of photofragment angular distributions have been
      performed as a function of the frequency of excitation, the lifetime of the
      dissociative state, the rotational level, and the rotational constant. In the
      limit of high J values and white, incoherent excitation, the general results are
      found to agree exactly with both those of Mukamel and Jortner [J. Chem. Phys. 61,
      5348 (1974)] and those of Jonah [J. Chem. Phys. 55, 1915 (1971)]. Example
      calculations describe how the anisotropy is dependent on the degree of
      broadening, the rotational constant, the initial rotational level, and the
      frequency of excitation. Applications are also made to interpret experimental
      results on the photodissociation of ClO via the 11-0, 10-0, and 6-0 bands of the
      A 2Pi3/2 -X 2Pi3/2 transition and on the photodissociation of O2 via the 0-0 band
      of the E 3Sigmau- -X 3Sigmag- transition.

PMID- 17029470
TI  - Dynamics of the 193 nm photodissociation of dichlorocarbene.
AB  - The dynamics of the 193 nm photodissociation of the CCl2 molecule have been
      investigated in a molecular beam experiment. The CCl2 parent molecule was
      generated in a molecular beam by pyrolysis of CHCl3, and both CCl2 and the CCl
      photofragment were detected by laser fluorescence excitation. The 193 nm
      attenuation cross section was estimated from the reduction of the CCl2 signal as
      a function of the photolysis laser fluence. The internal state distribution of
      the CCl photofragment was derived from analysis of laser fluorescence excitation
      spectra in the A 2Delta-X 2Pi band system. Most of the energy available to the
      CCl(X 2Pi)+Cl fragments appears as translational energy. The CCl fragment
      rotational energy is much less than predicted in an impulsive model. The excited
      electronic state appears to dissociate indirectly, through coupling with a
      repulsive state arising from the ground-state CCl(X 2Pi)+Cl asymptote. The
      identity of the initially excited electronic state is discussed on the basis of
      what is known about the CCl2 electronic states.

PMID- 17029471
TI  - High resolution photofragment translational spectroscopy studies of the near
      ultraviolet photolysis of phenol.
AB  - The fragmentation dynamics of gas phase phenol molecules following excitation at
      many wavelengths in the range 279.145 > or = lambdaphot > or = 206.00 nm have
      been investigated by H Rydberg atom photofragment translational spectroscopy.
      Many of the total kinetic energy release (TKER) spectra so derived show
      structure, the analysis of which confirms the importance of O-H bond fission and
      reveals that the resulting phenoxyl cofragments are formed in a very limited
      subset of their available vibrational state density. Spectra recorded at
      lambdaphot > or = 248 nm show a feature centered at TKER approximately 6500 cm(
      1). These H atom fragments, which show no recoil anisotropy, are rationalized in
      terms of initial S1<--S0 (pi*<--pi) excitation, and subsequent dissociation via
      two successive radiationless transitions: internal conversion to ground (S0)
      state levels carrying sufficient O-H stretch vibrational energy to allow
      efficient transfer towards, and passage around, the conical intersection (CI)
      between the S0 and S2(1pisigma*) potential energy surfaces (PESs) at larger R(O
      H), en route to ground state phenoxyl products. The observed phenoxyl product
      vibrations indicate that parent modes nu16a and nu11 can both promote
      nonadiabatic coupling in the vicinity of the S0S2 CI. Spectra recorded at
      lambdaphot < or = 248 nm reveal a faster, anisotropic distribution of recoiling H
      atoms, centered at TKER approximately 12,000 cm(-1). These we attribute to
      H+phenoxyl products formed by direct coupling between the optically excited
      S1(1pi pi*) and repulsive S2(1pi sigma*) PESs. Parent mode nu16b is identified as
      the dominant coupling mode at the S1/S2 CI, and the resulting phenoxyl radical
      cofragments display a long progression in nu18b, the C-O in-plane wagging mode.
      Analysis of all structured TKER spectra yields D0(H-OC6H5) = 30,015 +/- 40 cm(
      1). The present findings serve to emphasize two points of wider relevance in
      contemporary organic photochemistry: (i) The importance of 1) pi sigma* states in
      the fragmentation of gas phase heteroaromatic hydride molecules, even in cases
      where the 1pi sigma* state is optically dark. (ii) The probability of observing
      strikingly mode-specific product formation, even in "indirect" predissociations,
      if the fragmentation is driven by ultrafast nonadiabatic couplings via CIs
      between excited (and ground) state PESs.

PMID- 17029472
TI  - 248 nm photolysis of CH2Br2 by using cavity ring-down absorption spectroscopy:
      Br2 molecular elimination at room temperature.
AB  - Following photodissociation of CH2Br2 at 248 nm, Br2 molecular elimination is
      detected by using a tunable laser beam, as crossed perpendicular to the
      photolyzing laser beam in a ring-down cell, probing the Br2 fragment in the B
      3Piou+ -X 1Sigmag+ transition. The nascent vibrational population is obtained,
      yielding a population ratio of Br2(v = 1)Br2(v = 0) to be 0.7 +/- 0.2. The
      quantum yield for the Br2 elimination reaction is determined to be 0.2 +/- 0.1.
      Nevertheless, when CH2Br2 is prepared in a supersonic molecular beam under cold
      temperature, photofragmentation gives no Br2 detectable in a time-of-flight mass
      spectrometer. With the aid of ab initio potential energy calculations, a
      plausible pathway is proposed. Upon excitation to the 1B1 or 3B1 state, C-Br bond
      elongation may change the molecular symmetry of Cs and enhance the resultant 1
      1,3A'-X 1A' (or 1 1,3B1-X 1A1 as C2v is used) coupling to facilitate the process
      of internal conversion, followed by asynchronous concerted photodissociation.
      Temperature dependence measurements lend support to the proposed pathway.

PMID- 17029473
TI  - Explosive photodissociation of methane induced by ultrafast intense laser.
AB  - A new type of molecular fragmentation induced by femtosecond intense laser at the
      intensity of 2 x 10(14) W/cm2 is reported. For the parent molecule of methane,
      ethylene, n-butane, and 1-butene, fluorescence from H (n = 3-->2), CH (A 2Delta,
      B 2Sigma-, and C 2Sigma+-->X 2Pi), or C2 (d 3Pi g-->a 3Pi u) is observed in the
      spectrum. It shows that the fragmentation is a universal property of neutral
      molecule in the intense laser field. Unlike breaking only one or two chemical
      bonds in conventional UV photodissociation, the fragmentation caused by the
      intense laser undergoes vigorous changes, breaking most of the bonds in the
      molecule, like an explosion. The fragments are neutral species and cannot be
      produced through Coulomb explosion of multiply charged ion. The laser power
      dependence of CH (A-->X) emission of methane on a log-log scale has a slope of 10
      +/- 1. The fragmentation is thus explained as multiple channel dissociation of
      the superexcited state of parent molecule, which is created by multiphoton
      excitation.

PMID- 17029474
TI  - The time scale for electronic reorganization upon sudden ionization of the water
      and water-methanol hydrogen bonded dimers and of the weakly bound NO dimer.
AB  - When the valence molecular orbital is localized sudden ionization can cause the
      nascent hole to move rapidly even before any relaxation of the geometry occurs.
      Hydrogen bonded clusters offer suitable test systems where the hole is initially
      localized on one moiety. Computational studies are reported for the water dimer
      and water-methanol bimer. The local ionization potential of water is different in
      the methanol-water and water-methanol conformers and this difference is very
      clearly reflected in the dynamics of charge migration. For the NO dimer the
      results are that its structure is symmetric so that the two NO molecules are
      equivalent and do not exhibit the required localization. The role of symmetry is
      also evident in the charge propagation for holes created in different orbitals.
      Localization of the initial hole distribution even if absent in the bare molecule
      can still be induced by the intense electric field of a sudden photoionization.
      This effect is computationally studied for the NO dimer in the presence of a
      static electric field.

PMID- 17029475
TI  - Applied reaction dynamics: efficient synthesis gas production via single
      collision partial oxidation of methane to CO on Rh111.
AB  - Supersonic molecular beams have been used to determine the yield of CO from the
      partial oxidation of CH4 on a Rh111 catalytic substrate, CH4+12O2-->CO+2H2, as a
      function of beam kinetic energy. These experiments were done under ultrahigh
      vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that
      there was only a single collision for the CH4 to react with the surface. The
      fraction of CH4 converted is strongly dependent on the normal component of the
      incident beam's translational energy, and approaches unity for energies greater
      than approximately 1.3 eV. Comparison with a simplified model of the methane
      Rh111 reactive potential gives insight into the barrier for methane dissociation.
      These results demonstrate the efficient conversion of methane to synthesis gas,
      CO+2H2, are of interest in hydrogen generation, and have the optimal
      stoichiometry for subsequent utilization in synthetic fuel production (Fischer
      Tropsch or methanol synthesis). Moreover, under the reaction conditions explored,
      no CO2 was detected, i.e., the reaction proceeded with the production of very
      little, if any, unwanted greenhouse gas by-products. These findings demonstrate
      the efficacy of overcoming the limitations of purely thermal reaction mechanisms
      by coupling nonthermal mechanistic steps, leading to efficient C-H bond
      activation with subsequent thermal heterogeneous reactions.

PMID- 17029476
TI  - The collimation angle shift of desorbing product N2 in a steady-state N2O+CO
      reaction on Rh(110).
AB  - The angular distribution of desorbing product N2 was studied in N2O
      decompositions on Rh(110) in the temperature range of 60-700 K. The N2 desorption
      collimates along 62 degrees -68 degrees off normal toward either the [001] or
      [001] direction in a transient N2O decomposition below ca. 470 K or in the steady
      state N2O+CO reaction above 540 K. In the steady-state reaction at the
      temperature from ca. 470 to 540 K, however, the collimation angle shifts from 62
      degrees to 45 degrees with decreasing surface temperature. This angle shift is
      ascribed to the steric hindrance by coadsorbed CO because the N2 collimation in
      transient N2O decomposition at around 65 degrees is recovered in the range of 380
      500 K by an abrupt CO pressure drop followed by the decrease in CO coverage. N2O
      is oriented along the [001] direction before dissociation. A scattering model of
      the nascent N2 by adsorbed CO is proposed, yielding smaller collimation angles.

PMID- 17029477
TI  - Infrared spectroscopy of large ammonia clusters as a function of size.
AB  - We have measured the vibrational spectra of large ammonia (NH3)n clusters by
      photofragment spectroscopy in the spectral range from 3150 to 3450 cm(-1) for the
      average sizes n = 29, 80, 212, 447, and 989 and by depletion spectroscopy for
      n=8. The spectra are dominated by peaks around 3385 cm(-1) which are attributed
      to the asymmetric nu3 NH-stretch mode. Two further peaks between 3200 and 3260
      cm(-1) have about equal intensity for n = 8 and 29, but only about 0.40 of the
      intensity of the nu3 peak for the larger sizes. The spectra for the smallest and
      largest size agree with those obtained by Fourier transform infrared spectroscopy
      in slit jet expansion and collision cells, respectively. By accompanying
      calculation we demonstrate that the energetic order of the spectral features
      originating from the bending overtone 2nu4 and the symmetric NH-stretch nu1 in
      the range from 3150 to 3450 cm(-1) is changed between n = 10 and 100, while the
      asymmetric NH-stretch nu3 only exhibits a moderate redshift. The reason is the
      coupling of the ground state modes to the overtones.

PMID- 17029478
TI  - How many metal atoms are needed to dehydrogenate an ethylene molecule on metal
      clusters?: Correlation between reactivity and electronic structures of Fen+,
      Con+, and Nin+.
AB  - The absolute cross section for dehydrogenation of an ethylene molecule on Mn+
      [Fen+ (n = 2-28), Con+ (n = 8-29), and Nin+ (n = 3-30)] was measured as a
      function of the cluster size n in a gas-beam geometry at a collision energy of
      0.4 eV in the center-of-mass frame in an apparatus equipped with a tandem-type
      mass spectrometer. It is found that (1) the dehydrogenation cross section
      increases rapidly above a cluster size of approximately 18 on Fen+, approximately
      13 and approximately 18 on Con+, and approximately 10 on Nin+ and (2) the rapid
      increase of the cross section for Mn+ occurs at a cluster size where the 3d
      electrons start to contribute to the highest occupied levels of Mn+. These
      findings lead us to conclude that the 3d electrons of Mn+ play a central role in
      the dehydrogenation on Mn+.

PMID- 17029479
TI  - Time-resolved study of solvent-induced recombination in photodissociated IBr
      (CO2)n clusters.
AB  - We report the time-resolved recombination of photodissociated IBr-(CO2)n (n = 5
      10) clusters following excitation to the dissociative IBr-A' 2Pi12 state of the
      chromophore via a 180 fs, 795 nm laser pulse. Dissociation from the A' state of
      the bare anion results in I- and Br products. Upon solvation with CO2, the IBr-
      chromophore regains near-IR absorption only after recombination and vibrational
      relaxation on the ground electronic state. The recombination time was determined
      by using a delayed femtosecond probe laser, at the same wavelength as the pump,
      and detecting ionic photoproducts of the recombined IBr- cluster ions. In sharp
      contrast to previous studies involving solvated I2-, the observed recombination
      times for IBr-(CO2)n increase dramatically with increasing cluster size, from 12
      ps for n = 5 to 900 ps for n = 8,10. The nanosecond recombination times are
      especially surprising in that the overall recombination probability for these
      cluster ions is unity. Over the range of 5-10 solvent molecules, calculations
      show that the solvent is very asymmetrically distributed, localized around the Br
      end of the IBr- chromophore. It is proposed that this asymmetric solvation delays
      the recombination of the dissociating IBr-, in part through a solvent-induced
      well in the A' state that (for n = 8,10) traps the evolving complex. Extensive
      electronic structure calculations and nonadiabatic molecular dynamics simulations
      provide a framework to understand this unexpected behavior.

PMID- 17029480
TI  - Photodissociation of polycrystalline and amorphous water ice films at 157 and 193
      nm.
AB  - The photodissociation dynamics of amorphous solid water (ASW) films and
      polycrystalline ice (PCI) films at a substrate temperature of 100 K have been
      investigated by analyzing the time-of-flight (TOF) mass spectra of photofragment
      hydrogen atoms at 157 and 193 nm. For PCI films, the TOF spectrum recorded at 157
      nm could be characterized by a combination of three different (fast, medium, and
      slow) Maxwell-Boltzmann energy distributions, while that measured at 193 nm can
      be fitted in terms of solely a fast component. For ASW films, the TOF spectra
      measured at 157 and 193 nm were both dominated by the slow component, indicating
      that the photofragment H atoms are accommodated to the substrate temperature by
      collisions. H atom formation at 193 nm is attributed to the photodissociation of
      water species on the ice surface, while at 157 nm it is ascribable to a mixture
      of surface and bulk photodissociations. Atmospheric implications in the high
      latitude mesopause region of the Earth are discussed.

PMID- 17029481
TI  - Molecular dynamics of haloalkane corral formation and surface halogenation at
      Si(111)-7 x 7.
AB  - Long-chain organic molecules, 1-halododecane, RX (X = Cl,Br), adsorbed on Si(111)
      7 x 7 were shown to form stable dimeric corrals; type I around corner holes and
      type II around corner adatoms S. Dobrin et al. [Surf. Sci. Lett. 600, L43
      (2006)]. Here we examine the molecular dynamics of corral formation, in which
      mobile physisorbed adsorbates spontaneously convert to immobile. At high coverage
      the mechanism gives evidence of involving collisions between mobile vertical
      monomers, giving types I and II immobile horizontal dimers, vD +vD -->h2 (I, II).
      At low coverage mobile vertical monomers collide with immobile horizontal ones to
      form largely type-II corrals, vD + h-->h2 (II). Thermal reaction of corrals with
      X = Br brominates the surface by two distinct molecular pathways, thought to have
      more general applicability: "daughter-mediated" reaction of vertical v(A) with a
      low activation energy (here Ea approximately 5 kcal mol(-1)) and "parent
      mediated" reaction of horizontal h or h2 with high activation energy (here Ea =
      29 kcal mol(-1)).

PMID- 17029482
TI  - Ultrafast vectorial and scalar dynamics of ionic clusters: azobenzene solvated by
      oxygen.
AB  - The ultrafast dynamics of clusters of trans-azobenzene anion (A-) solvated by
      oxygen molecules was investigated using femtosecond time-resolved photoelectron
      spectroscopy. The time scale for stripping off all oxygen molecules from A- was
      determined by monitoring in real time the transient of the A- rise, following an
      800 nm excitation of A- (O2)n, where n = 1-4. A careful analysis of the time
      dependent photoelectron spectra strongly suggests that for n > 1 a quasi-O4 core
      is formed and that the dissociation occurs by a bond cleavage between A- and
      conglomerated (O2)n rather than a stepwise evaporation of O2. With time and
      energy resolutions, we were able to capture the photoelectron signatures of
      transient species which instantaneously rise (<100 fs) then decay. The transient
      species are assigned as charge-transfer complexes: A.O2- for A- O2 and A.O4-(O2)n
      2 for A-(O2)n, where n = 2-4. Subsequent to an ultrafast electron recombination,
      A- rises with two distinct time scales: a subpicosecond component reflecting a
      direct bond rupture of the A- -(O2)n nuclear coordinate and a slower component
      (1.6-36 ps, increasing with n) attributed to an indirect channel exhibiting a
      quasistatistical behavior. The photodetachment transients exhibit a change in the
      transition dipole direction as a function of time delay. Rotational dephasing
      occurs on a time scale of 2-3 ps, with a change in the sign of the transient
      anisotropy between A- O2 and the larger clusters. This behavior is a key
      indicator of an evolving cluster structure and is successfully modeled by
      calculations based on the structures and inertial motion of the parent clusters.

PMID- 17029483
TI  - A mass and time-of-flight spectroscopy study of the formation of clusters in free
      jet expansions of normal D2.
AB  - The mass spectra in the range of 2(D+)-38(D19+) amu of clusters formed in a
      supersonic free-jet expansion of normal D2 are investigated as functions of
      source temperature in the range of 95-220 K and of source pressure in the range
      of 10-120 bars. For some of the small ion fragments, time-of-flight distributions
      are also measured. For large clusters (n > 200) the intensities of the odd
      numbered ion fragments exhibit magic numbers at D9+ and D15+ in accordance with
      previous experiments and calculations. The even-numbered ion fragments have much
      smaller intensities and exhibit new magic numbers at D10+ and D14+. For source
      conditions such that large clusters are formed, the intensities of the various
      different ion fragments are observed to saturate beyond a certain source
      pressure. At lower source pressures, where only small clusters are formed, the
      terminal mole fractions of the neutral dimers are analyzed in the light of
      available theories which take into account both the thermodynamics and the
      kinetics of the expansion. At higher source pressures and lower temperatures,
      where larger clusters are formed, the sizes of the neutral clusters are estimated
      using scaling laws and are found to be consistent with the mass spectra and
      measured time-of-flight distributions. By using a variety of techniques it has
      been possible to obtain reliable conclusions about the neutral cluster sizes for
      the present free-jet expansion conditions.

PMID- 17029484
TI  - Manipulation of slow molecular beams by static external fields.
AB  - Deflection by magnetic or electric field gradients has long been used to analyze
      or to alter the translational trajectories of neutral gas-phase atoms or
      molecules. Recent work has developed sources of slow, cold molecular beams that
      offer means to enhance markedly the attainable deflections, which are inversely
      proportional to the translational kinetic energy. The sensitivity and resolution
      can thus be much increased, typically by factors of 10(2)-10(4). We illustrate
      ways to exploit this enhanced deflection capability, particularly when balancing
      electric and magnetic deflections. Chemical scope can be greatly extended by
      utilizing feeble but ubiquitous interactions, especially the induced electric
      dipole due to the molecular polarizability and magnetic moments resulting from
      molecular rotation or nuclear spins. We also examine the effect of non-Maxwellian
      velocity distributions produced by supersonic expansions or by quantum statistics
      (pertinent for ultracold beams). Generic plots are provided, employing
      dimensionless variables, to facilitate the design and interpretation of
      experiments with deflections amplified by low kinetic energy.

PMID- 17029485
TI  - A new time evolving Gaussian series representation of the imaginary time
      propagator.
AB  - Frantsuzov and Mandelshtam [J. Chem. Phys. 121, 9247 (2004)] have recently
      demonstrated that a time evolving Gaussian approximation (TEGA) to the imaginary
      time propagator exp(-betaH) is useful for numerical computations of
      anharmonically coupled systems with many degrees of freedom. In this paper we
      derive a new exact series representation for the imaginary time propagator whose
      leading order term is the TEGA. One can thus use the TEGA not only as an
      approximation but also to obtain the exact imaginary time propagator. We also
      show how the TEGA may be generalized to provide a family of TEGA's. Finally, we
      find that the equations of motion governing the evolution of the center and width
      of the Gaussian may be thought of as introducing a quantum friction term to the
      classical evolution equations.

PMID- 17029486
TI  - Construction and calibration of an instrument for three-dimensional ion imaging.
AB  - We describe a new instrument based on a delay-line detector for imaging the
      complete three-dimensional velocity distribution of photoionized products from
      photoinitiated reactions. Doppler-free [2+1] resonantly enhanced multiphoton
      ionization (REMPI) of H and D atoms formed upon photolysis of HBr and DBr in the
      range 203 nm < or = lambda photolysis < or = 243 nm yields radial speeds measured
      to be accurate within 1% of those calculated. The relative speed resolution is
      about 5% and limited by photoionization recoil broadening. A relative speed
      resolution of 3.4% is obtained for [3+1] REMPI, which minimizes the ionization
      recoil. We also determine the branching ratio between ground-state and spin-orbit
      excited product channels and their associated anisotropies. We find that DBr
      photolysis dynamics differs slightly from its HBr counterpart.

PMID- 17029487
TI  - Local angular momentum-local impact parameter analysis: derivation and properties
      of the fundamental identity, with applications to the F+H2, H+D2, and Cl+HCl
      chemical reactions.
AB  - The technique of local angular momentum-local impact parameter (LAM-LIP) analysis
      has recently been shown to provide valuable dynamical information on the angular
      scattering of chemical reactions under semiclassical conditions. The LAM-LIP
      technique exploits a nearside-farside (NF) decomposition of the scattering
      amplitude, which is assumed to be a Legendre partial wave series. In this paper,
      we derive the "fundamental NF LAM identity," which relates the full LAM to the NF
      LAMs (there is a similar identity for the LIP case). Two derivations are
      presented. The first uses complex variable techniques, while the second exploits
      an analogy between the motion of the scattering amplitude in the Argand plane
      with changing angle and the classical mechanical motion of a particle in a plane
      with changing time. Alternative forms of the fundamental LAM-LIP identity are
      described, one of which gives rise to a CLAM-CLIP plot, where CLAM denotes (Cross
      section) x LAM and CLIP denotes (Cross section) x LIP. Applications of the NF LAM
      theory, together with CLAM plots, are reported for state-to-state transitions of
      the benchmark reactions F+H2-->FH+H, H+D2-->HD+D, and Cl+HCl-->ClH+Cl, using as
      input both numerical and parametrized scattering matrix elements. We use the
      fundamental LAM identity to explain the important empirical observation that a NF
      cross section analysis and a NF LAM analysis provide consistent (and
      complementary) information on the dynamics of chemical reactions.

PMID- 17029488
TI  - Numerical generation of hyperspherical harmonics for tetra-atomic systems.
AB  - A numerical generation method of hyperspherical harmonics for tetra-atomic
      systems, in terms of row-orthonormal hyperspherical coordinates-a hyper-radius
      and eight angles-is presented. The nine-dimensional coordinate space is split
      into three three-dimensional spaces, the physical rotation, kinematic rotation,
      and kinematic invariant spaces. The eight-angle principal-axes-of-inertia
      hyperspherical harmonics are expanded in Wigner rotation matrices for the
      physical and kinematic rotation angles. The remaining two-angle harmonics defined
      in kinematic invariant space are expanded in a basis of trigonometric functions,
      and the diagonalization of the kinetic energy operator in this basis provides
      highly accurate harmonics. This trigonometric basis is chosen to provide a
      mathematically exact and finite expansion for the harmonics. Individually, each
      basis function does not satisfy appropriate boundary conditions at the poles of
      the kinetic energy operator; however, the numerically generated linear
      combination of these functions which constitutes the harmonic does. The size of
      this basis is minimized using the symmetries of the system, in particular,
      internal symmetries, involving different sets of coordinates in nine-dimensional
      space corresponding to the same physical configuration.

PMID- 17029489
TI  - The integration of measurement and management for the treatment of bipolar
      disorder: a STEP-BD model of collaborative care in psychiatry.
AB  - Patients with bipolar disorder are among the most challenging to treat. These
      patients frequently present with complex mood and other symptoms that change over
      time, complex psychiatric and medical comorbid conditions, and multiple
      medications. Clinicians rarely systematically assess or measure all of these
      factors and instead rely on memory and general impressions. It is imperative that
      clinicians systematically track and monitor these relevant variables to ensure
      treatment decisions are based on precise clinical data. By integrating
      measurement and management, clinicians and patients can collaborate to assess the
      effectiveness of treatments and to make joint decisions about critical points at
      which to adjust treatment. This method was shown to be successful in the National
      Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for
      Bipolar Disorder (STEP-BD).

PMID- 17029490
TI  - Illness course, comorbidity, gender, and suicidality in patients with bipolar
      disorder.
AB  - Among patients with bipolar disorder, comorbid conditions are common. Comorbidity
      is associated with a more difficult course of illness (such as longer episodes,
      shorter time euthymic, and earlier age at onset) and an increase in related
      problems (such as suicidality and violence). Data from the Systematic Treatment
      Enhancement Program for Bipolar Disorder (STEP-BD) reveal that anxiety disorders,
      attention-deficit/hyperactivity disorder, and substance and alcohol use disorder
      are conditions that commonly co-occur with bipolar disorder. This article details
      these findings and discusses the complications associated with these comorbid
      conditions. STEP-BD data about gender differences are also discussed, and
      correlates of suicidal ideation among patients entering the program are
      described.

PMID- 17029491
TI  - Implementing evidence-based treatment of manic and mixed episodes.
AB  - Manic and mixed episodes can be challenging to treat despite published guidelines
      and algorithms. An alternative iterative approach that offers evidence-based
      treatment options at critical decision points may help to individualize care.
      Implementing such an approach begins with making a diagnosis and recognizing
      individual patient factors, weighing treatment options, and developing a menu of
      reasonable treatment choices based on the best available evidence. A critical
      review of the evidence is needed to ensure that interventions with the highest
      quality evidence are offered preferentially and that relevant individual factors
      are considered. Educating patients, negotiating treatment options, and selecting
      a pathway of care with the patient are important steps before initiating an
      intervention. After initiating an intervention, follow-up proceeds by measuring
      efficacy and adverse events with the aim of determining whether or not the
      patient is benefiting from treatment. Based on this knowledge, new individual
      factors are known and new evidence can be reviewed, so the cycle begins again.
      Using this iterative approach to treat patients with bipolar disorder in manic
      and mixed episodes promotes personalized care and relies on understanding the
      quality of evidence for the treatments commonly used to treat these phases of
      bipolar disorder.

PMID- 17029492
TI  - The evidence for antidepressant use in bipolar depression.
AB  - Mood elevation, which includes mania, hypomania, and mixed states, was previously
      considered the defining symptom of bipolar disorder, but bipolar depression by
      comparison is actually a much more substantial challenge to diagnose and treat.
      Recent studies, including research by the Systematic Treatment Enhancement
      Program for Bipolar Disorder (STEP-BD), found that patients with bipolar disorder
      spend longer periods of time in depressive episodes and are more likely to
      relapse to depression compared with mania or hypomania. However, the treatment of
      bipolar depression is hampered by the limited number and varying quality of
      available studies of pharmacologic treatments to guide clinical decision making.
      Clinicians should rely on studies with the highest level of evidence (category A)
      when prescribing appropriate antidepressant treatments. The standard care
      pathways outlined by STEP-BD to aid clinicians in treating varying phases of
      bipolar disorder provide data on the use of various treatments for bipolar
      depression and their outcomes. While some treatments have the potential to induce
      mania, others appear to have some efficacy without inducing mania.

PMID- 17029493
TI  - Treatment of rapid-cycling bipolar disorder.
AB  - Rapid-cycling bipolar disorder is associated with poorer treatment response,
      poorer long-term prognosis, and probable higher suicide risk than bipolar
      disorder without rapid cycling. Patients with rapid cycling tend to experience
      more depressive than manic episodes, and the depressive episodes tend to be more
      refractory in nature compared with those in patients without rapid cycling.
      Results from studies of rapid cycling show that antidepressant use is most likely
      associated with the onset or worsening of rapid cycling. Controversy also exists
      as to whether rapid cycling is a transitory phenomenon in the course of bipolar
      illness or a more chronic condition better characterized as a subtype of the
      illness. Results from the first 500 patients with bipolar I or bipolar II
      disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD) study found an association between rapid cycling and
      depression and younger age at illness onset. Treatment involves a 3-part pathway
      to manage rapid cycling that includes reducing or stopping any possible cycle
      promoting agents, adding or optimizing mood stabilizers, and using experimental
      or putative treatments for persistent rapid cycling after more traditional
      treatments have failed. Effective treatments for some patients with rapid-cycling
      bipolar disorder currently include lithium, divalproex, lamotrigine,
      carbamazepine, atypical antipsychotics, and psychosocial therapy.

PMID- 17029494
TI  - A review of evidence-based psychosocial interventions for bipolar disorder.
AB  - Various forms of psychosocial intervention have been found efficacious as
      adjunctive treatments for bipolar disorder, including family-focused therapy,
      interpersonal and social rhythm therapy, cognitive-behavioral therapy, and
      individual or group psychoeducation. When used in conjunction with
      pharmacotherapy, these interventions may prolong time to relapse, reduce symptom
      severity, and increase medication adherence. Family-focused therapy seeks to
      reduce the high levels of stress and conflict in the families of bipolar
      patients, thereby improving the patient's illness course. Interpersonal and
      social rhythm therapy focuses on stabilizing the daily and nightly routines of
      bipolar patients and resolving key interpersonal problems. Cognitive-behavioral
      therapy assists patients in modifying dysfunctional cognitions and behaviors that
      may aggravate the course of bipolar disorder. Group psychoeducation provides a
      supportive, interactive setting in which patients learn about their disorder and
      how to cope with it. This article discusses each of these interventions and
      summarizes the evidence for their efficacy in randomized trials. Recommendations
      for implementing psychosocial interventions in clinical practice are also given.

PMID- 17029495
TI  - Phytochrome-mediated inhibition of coleoptile growth in rice: age-dependency and
      action spectra.
AB  - Phytochrome has been shown to be the major photoreceptor involved in the photo
      inhibition of coleoptile growth in Japonica-type rice (Oryza sativa L.). We have
      characterized this typical photomorphogenetic response of rice using mutants
      deficient in phytochrome A (phyA) and phytochrome B (phyB) and with respect to
      age-dependency and action spectra. Seedlings were irradiated with a pulse of
      light 40 h or 80 h after germination (i.e. at an early or late developmental
      stage) and the final coleoptile length of these seedlings was determined. A
      saturating pulse of red light (R) had a stronger effect when it was given in the
      late stage than in the early stage. It was found that the photoinhibition is
      mediated by both the phyA and the phyB in the late stage but predominantly by
      phyB in the early stage. Consistent with many other reported responses, the photo
      inhibition in the phyA mutant, which was observed in the early and late
      developmental stages and is thought to be mediated mainly by phyB, occurred in
      the low-fluence range (10(1)-10(3) micromol m(-2)) of R and was far-red-light
      (FR)-reversible; the photo-inhibition in the phyB mutant, which was observed in
      the late developmental stage and is thought to be mediated mainly by phyA,
      occurred in the very-low-fluence range (10(-2)-10(0) micromol m(-2)) and was FR
      irreversible. The action spectra (350-800 nm at 50 nm intervals) obtained at the
      two developmental stages using phyA and phyB mutants indicated that both the phyB
      mediated low-fluence response and the phyA-mediated very-low-fluence response
      have a major peak at 650 nm and a minor peak at 400 nm.

PMID- 17029496
TI  - Energy transfer from chemically attached rhodamine 101 to adsorbed methylene blue
      on microcrystalline cellulose particles.
AB  - Rhodamine 101 (R101) was chemically attached onto microcrystalline cellulose and
      methylene blue (MB) was adsorbed to a sample bearing nearby 6 x 10(-7) mol R101
      (g cellulose)(-1). The system was studied by reflectance and emission
      spectroscopy in the solid state. R101 shows no aggregation in these conditions
      and, while pure MB builds up dimers on cellulose even at 2 x 10(-8) mol g(-1), in
      the presence of R101 no evidence on selfaggregation or heteroaggregation is found
      up to around 10(-6) mol g(-1). No exciplex formation is found as well. The
      overall fluorescence quantum yield measured on thick layers, once re-absorption
      effects are accounted for, amounts to 0.80 +/- 0.07 for pure R101 and decreases
      steadily on increasing the concentration of MB. Results demonstrate the
      occurrence of radiative and nonradiative singlet energy transfer from R101 to MB.
      For thick layers of particles, the combined effect of both kinds of energy
      transfer amounts to nearly 80% at the highest acceptor concentration, while
      nonradiative transfer reaches 60% both for thin and optically thick layers. The
      dependence of nonradiative energy transfer efficiencies on the acceptor
      concentration is analyzed and the origin of departures from Forster behavior at
      low acceptor concentration is discussed.

PMID- 17029497
TI  - Inhibition of return and negative priming by persons with and without mental
      retardation.
AB  - Persons with and without mental retardation who were matched on CA took part in
      three tasks: an inhibition of return task, a location negative-priming task, and
      an identity negative-priming task. Having participants perform all three tasks
      allowed us to correlate performance among the tasks and assess the various
      relationships among performance measures on negative priming and inhibition of
      return. The participants with mental retardation did not exhibit negative priming
      of identity. However, they did exhibit negative priming of location and
      inhibition of return. The participants without mental retardation exhibited all
      three effects. A different pattern of correlations was observed for the
      participants with and those without mental retardation. Possible reasons for this
      difference are discussed.

PMID- 17029499
TI  - Broad cognitive abilities of children with mental retardation: an analysis of
      group and individual profiles.
AB  - Group and individual broad ability profiles of children with mental retardation
      and a matched sample of children with average achievement was investigated
      through use of the 7 Cattell-Horn-Carroll (CHC) factor clusters from the Woodcock
      Johnson III Tests of Cognitive Abilities. Results indicate that, as a group, the
      ranked performance of the children with mental retardation on the CHC factor
      clusters was largely consistent with the clusters' g loadings. When compared to
      average-achieving matches, the children with mental retardation scored lower on
      all CHC factor clusters, but the groups displayed different patterns of
      performance. Despite normative deficiencies in IQs, children with mental
      retardation demonstrated a wide range of performance across measures.
      Implications for assessment and diagnosis are discussed.

PMID- 17029498
TI  - Longitudinal analysis of the impact and cost of person-centered planning for
      people with intellectual disabilities in England.
AB  - Person-centered planning is central to United Kingdom policies regarding the
      support of people with intellectual disabilities. However, little evidence exists
      on the impact or cost of introducing person-centered planning. We examined the
      efficacy, effectiveness, and costs of introducing person-centered planning for 93
      people with intellectual disabilities over 2 years across four localities in
      England. A person-centered plan was successfully developed for 65 people. Little
      change was apparent prior to introducing person-centered planning. After its
      introduction, modest positive changes were found in the areas of social networks;
      contact with family; contact with friends; community-based activities; scheduled
      day activities; and choice. The direct training and support cost of introducing
      person-centered planning was $1,202 per participant; indirect costs were
      negligible.

PMID- 17029500
TI  - Interpreting kappa in observational research: baserate matters.
AB  - Kappa (Cohen, 1960) is a popular agreement statistic used to estimate the
      accuracy of observers. The response of kappa to differing baserates was examined
      and methods for estimating the accuracy of observers presented. Results suggest
      that setting a single value of kappa as "minimally acceptable" (i.e., a criterion
      value) is not useful in ensuring adequate accuracy of observers. Instead,
      researchers should use the best estimate of the true baserate of the target
      behavior and the obtained kappa to estimate the accuracy of observers.
      Investigators can then compare the estimated accuracy of observers to a
      preselected criterion level. Guidelines are given for selecting a criterion
      accuracy level.

PMID- 17029501
TI  - Effects of social stimuli on laughing and smiling in young children with Angelman
      syndrome.
AB  - The effects of social stimuli present and absent on laughing and smiling in 2
      young children with Angelman syndrome were assessed via a multielement design.
      Results indicated that laughing and smiling for either child was unaffected by
      the social stimuli assessed in the social interaction condition. Results are
      discussed in terms of the effects of biological variables and environmental
      stimuli on children with specific genetic disorders across the lifespan.

PMID- 17029502
TI  - Matching-to-sample assessment of stimulus overselectivity in students with
      intellectual disabilities.
AB  - A delayed matching-to-sample task with multiple sample stimuli was used to
      evaluate stimulus overselectivity in 70 individuals attending residential special
      education schools. A Mental Age Equivalent score (MAE) was obtained for each
      student using the Peabody Picture Vocabulary Test. Twenty-one participants failed
      to complete matching-to-sample pretests (mean MAE = 3.70 years). Results on the
      multiple-sample test for the remaining 49 participants indicated no
      overselectivity for 14 students (mean MAE = 7.44 years) and were consistent with
      overselectivity for 35 students (mean MAE = 5.28 years). Performances of students
      with overselectivity were more variable than those with no overselectivity. The
      MAE scores were related to both matching-to-sample performance and stimulus
      overselectivity.

PMID- 17029504
TI  - Lip shape and position in Class II division 2 malocclusion.
AB  - OBJECTIVE: To determine whether differences exist in the shape and position of
      the lips between Class II division 2 and Class I malocclusions. MATERIALS AND
      METHODS: Lateral cephalometric radiographs of subjects with Class II division 2
      (n = 30) and Class I (n = 30) incisor relationships were scanned at 300 dpi to
      produce digital images. These were subsequently digitized in random order. Twenty
      one landmarks characterizing the upper and lower lips and the maxillary and
      mandibular central incisors were digitized. Procrustes algorithms optimally
      superimposed the landmark configurations to standardize size, location, and
      orientation. Discriminant analysis of the principal components of shape
      determined the differences between the Class II division 2 and Class I groups.
      RESULTS: The shape and position of the upper and lower lips differed
      significantly between the Class II division 2 group and the Class I group (P <
      .001). Principal component (PC) 1 (46% of the variance) involved an increase in
      the thickness of the upper and lower lips in the Class II division 2 group. PC2
      (11% of the variance) was characterized by a relatively higher lip line in the
      Class II division 2 group. CONCLUSIONS: The shape and position of the lips differ
      between Class II division 2 and Class I malocclusions.

PMID- 17029505
TI  - Predictive factors of vertical bone depth in the paramedian palate of
      adolescents.
AB  - OBJECTIVE: To determine whether a relationship exists between the vertical bone
      depth in the paramedian palate (PP) of growing patients and age, gender, and
      palatal morphology. Clinically detectable traits may decrease the need for
      further imaging prior to implant placement for orthodontic anchorage. MATERIALS
      AND METHODS: Cone beam computed tomagraphic scans (Newtom-9000, Verona, Italy)
      were acquired in 183 orthodontic patients (10-19 years old). Vertical bone depth
      was measured at nine unilateral locations in the PP of each subject. Measurements
      were analyzed with univariate and multivariate statistical tests. RESULTS:
      Significant variability in the bone thickness was found among locations and among
      subjects. Male subjects had significantly greater mean bone thickness in six of
      the nine locations measured, showing a mean of 1.22 mm more vertical bone than
      females showed at these locations. Age and palatal measurements did not
      demonstrate a clinically useful relationship with bone depth. CONCLUSIONS: Age
      and palatal morphology are not valid predictors of bone height in the PP. Because
      of the large variability of bone thickness in this region, computed tomographic
      imaging remains valuable prior to paramedian implant placement in growing
      individuals. The paramedian palate presents a promising region for palatal
      implant placements when the midpalatal suture is to be avoided.

PMID- 17029506
TI  - Correlations between rapid maxillary expansion (RME) and the auditory apparatus.
AB  - OBJECTIVE: To evaluate the effects of rapid maxillary expansion (RME) on
      conductive hearing loss and maxillary constriction. MATERIALS AND METHODS: A
      total of 25 subjects (15 girls and 10 boys, aged between 6 years 8 months to 8
      years 2 months) with conductive hearing loss and maxillary constriction were
      studied. Audiogram, tympanogram, and video-otoscopy were used to investigate the
      anatomical and physiological modifications of the bony and muscular structure of
      the maxilla and the auditory apparatus. The records were taken before maxillary
      expansion (T0), after expansion (7-14 days; T1), and after the retention period
      (8 months after expansion; T2). RESULTS: After expansion, the audiometric records
      indicated an improvement in hearing levels for higher frequencies but not for
      lower ones. After the retention period, there was a functional improvement in all
      patients for all frequencies. The recovery of the tympanic membrane's elasticity
      occurred only after retention, as shown by the standard model tympanogram, which
      was still flat after expansion. CONCLUSIONS: The auditory function in patients
      with conductive hearing loss may be corrected through correction of the palatal
      anatomy, which influences the muscular function of the tubal ostia and allows a
      normal activity of the tympanic membrane and the auditory apparatus. Positive
      effects on conductive hearing loss are possible additional benefits of RME
      treatment, but this does not indicate that patients with conductive hearing loss
      without an accompanying maxillary constriction should consider this as a
      treatment approach.

PMID- 17029507
TI  - Nonsurgical rapid maxillary expansion effects on craniofacial structures in young
      adult females. A bone scintigraphy study.
AB  - OBJECTIVE: To evaluate the skeletal effects of nonsurgical rapid maxillary
      expansion (RME) on craniofacial structures with bone scintigraphy in young adult
      female subjects. MATERIALS AND METHODS: The material of the present study
      consists of scintigraphic records taken from 17 early adult females treated with
      RME. All patients had a bilateral posterior crossbite, transverse maxillary
      deficiency, deep palatal vault, and dental crowding at the beginning of the
      treatment. The age range of the patients was 16.1 to 18.8 years, and the mean age
      was 17.3 +/- 0.86 years. Bone scintigraphy records were obtained before RME (T1),
      during the splitting of the midpalatal suture (T2), and after the end of active
      widening period (T3). Repeated measure analysis of variance was used to assess
      the differences between the periods. In addition, Bonferroni multiple comparison
      tests were applied to the measurements at which F values were found to be
      statistically significant. RESULTS: According to the statistical analysis,
      significant activity changes were found in all regions studied and in all slices.
      The metabolic activity in all regions showed significant increases up to the
      separation of the midpalatal suture (T1-T2), whereas the metabolic activity
      exhibited a remarkable decrease (T2-T3) after the opening of the midpalatal
      suture. CONCLUSIONS: Scintigraphic records revealed an increase in the regions of
      interest scores during RME in all regions and all slices. Therefore, it can be
      speculated that RME has had not only dental effects but also skeletal effects on
      young adult patients.

PMID- 17029508
TI  - Dental maturation in short and long facial types. Is there a difference?
AB  - OBJECTIVE: The purpose of this investigation was to study the relationship
      between vertical skeletal growth pattern and dental maturation in children with
      long or short anterior facial height. MATERIALS AND METHODS: The sample consisted
      of the records of 312 Dutch children (153 boys and 159 girls, aged 9-12.9 years,
      with a mean chronological age of 11.3 years). The subjects were selected
      according to their lower anterior facial height as a percentage of the total
      facial height. Two groups, one with long and the other with short anterior facial
      height, were formed for further comparison. Dental age, according to Demirjian's
      dental maturity score, was determined for each subject. The power of the study
      was 79% (2-sided test) and 87% (1-sided test). RESULTS: There was no
      statistically significant difference in dental age score between the two extreme
      groups. The subjects with short anterior facial height demonstrated a slight
      tendency toward more advanced dental age. CONCLUSIONS: The difference in dental
      age between long and short facial types is not big enough to be clinically
      relevant.

PMID- 17029509
TI  - Measuring adult facial morphology in three dimensions.
AB  - OBJECTIVES: The aim of this study is to evaluate the reliability of measuring
      three-dimensional soft tissue morphology using a laser imaging system. DESIGN:
      Prospective clinical trial. MATERIALS AND METHODS: Thirty-eight adult subjects,
      mean age 24.5 years, were analyzed for soft tissue changes at baseline (T1) and
      at 1 week (T2) using two commercially available Minolta Vivid 900 (Osaka, Japan)
      laser scanning devices assembled as a stereopair. Left and right images were
      merged to form the whole face, and these images were superimposed to assess the
      errors between the two faces at T1 and at T2. RESULTS: The results showed that
      the mean shell deviations for left and right scans at T1 were 0.32 +/- 0.08 mm
      and 0.30 +/- 0.09 mm for males and females, respectively. The mean shell
      deviations for left and right scans at T2 were 0.34 +/- 0.08 mm and 0.32 +/- 0.09
      mm for males and females, respectively. The mean difference of the merged
      composite faces superimposed at T1 and T2 was 0.37 +/- 0.07 mm and 0.35 +/- 0.09
      mm for males and females, respectively. Paired t-tests revealed that the mean
      difference of 0.02 mm was statistically insignificant (P > .05). The
      reproducibility error was 0.7 and 0.8 mm for females and males, respectively,
      when a tolerance of 90% was imposed on the aligned faces. CONCLUSIONS: Capturing
      soft tissue morphology of the face, using the technique described, is clinically
      reproducible within 1 week of the initial records.

PMID- 17029510
TI  - Relationship between thoracic, lordotic, and pelvic inclination and craniofacial
      morphology in adults.
AB  - OBJECTIVE: To analyze the correlation ratios between the spinal posture
      (thoracic, lordotic, and pelvic inclination) and the craniofacial morphology.
      MATERIALS AND METHODS: The sample consisted of 53 healthy adults (32 women, 21
      men; mean age 24.6 years). Six angular skeletal measurements (facial axis,
      mandibular plane angle, inner gonial angle, lower facial height, facial depth,
      and maxilla position) were determined based on the analysis of lateral head
      cephalographs. Rasterstereography was used for a precise reconstruction of the
      back sagittal profile. From the profile parameters, the upper thoracic
      inclination, the thoracic angle, the lordotic angle, and the pelvic inclination
      were determined. The correlations to the craniofacial morphology were calculated
      by means of the Pearson and Mann-Whitney U-test. RESULTS: Significant
      correlations could be obtained with respect to the facial axis and the lordotic
      angle, the facial axis and the pelvic inclination, the inner gonial angle and the
      lordotic angle, the inner gonial angle and the pelvic inclination, the mandibular
      plane angle and the lordotic angle, the mandibular plane angle and the pelvic
      inclination, as well as the facial depth and the pelvic inclination. CONCLUSIONS:
      In the case of postural disorders of the back shape, an interdisciplinary
      treatment approach seems to be of clinical value. Further prospective studies are
      necessary to prove how changes in craniofacial parameters can affect the postural
      balance of an individual.

PMID- 17029511
TI  - Mandibular growth during adolescence.
AB  - OBJECTIVE: To evaluate the mandibular growth of whites according to Fishman's
      method. MATERIALS AND METHODS: Eighty-five subjects, 9 to 18 years of age, were
      selected from the files of the Department of Orthodontics, Pontificia
      Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil. Patients were
      evaluated at two time points. At T1, they had a lateral head film and a hand
      wrist radiograph and at T2, a lateral head film. The interval between T1 and T2
      was 5 to 24 months. Subjects presented a Class I or II skeletal pattern and were
      divided into three groups according to Fishman's method: group I, in an
      accelerating growth velocity phase; group II, in peak of growth velocity phase;
      and group III, in decelerating growth velocity phase. The cephalograms were
      manually traced and cephalometric points digitalized into DentoFacial Planner
      Plus 2.0. The absolute growth amount was adjusted to obtain an annual growth rate
      (mm/y). The annual growth rate was compared between sexes, between individuals
      with Class I or II skeletal patterns, and among the three groups. RESULTS:
      Mandibular annual growth rate in puberty was 2.16 mm for the mandibular body
      length, 3.16 mm for the ramus height, and 4.31 mm for the mandibular length. The
      results did not show significant differences between sexes, skeletal patterns,
      and groups, although there was a tendency for growth acceleration in group II.
      CONCLUSIONS: There is great individual variation in mandibular linear growth.

PMID- 17029512
TI  - Customized three-dimensional computational fluid dynamics simulation of the upper
      airway of obstructive sleep apnea.
AB  - OBJECTIVE: To use computer simulations to describe the role of fluid dynamics in
      the human upper airway. MATERIALS AND METHODS: The model was constructed using
      raw data from three-dimensional (3-D) computed tomogram (CT) images of an
      obstructive sleep apnea (OSA) patient. Using Bionix software (CantiBio Inc.,
      Suwon, Korea), the CT data in DICOM format was transformed into an anatomically
      correct 3-D Computational fluid dynamic (CFD) model of the human upper airway.
      Once constructed, the model was meshed into 725,671 tetra-elements. The solution
      for testing was performed by the STAR-CD software (CD adapco group, New York,
      NY). Airflow was assumed to be turbulent at an inspiration rate of 170, 200, and
      230 ml/s per nostril. The velocity magnitude, relative pressure, and flow
      distribution was obtained. RESULTS: High airflow velocity predominated in medial
      and ventral nasal airway regions. Maximum air velocity (15.41 m/s) and lowest
      pressure (negative 110.8 Pa) were observed at the narrowest portions of the
      velopharynx. Considering differences in model geometry, flow rate, and reference
      sections, when airflow patterns in nasal cavity were compared, our results were
      in agreement with previous data. CONCLUSIONS: CFD analyses on airway CT data
      enhanced our understanding of pharyngeal aerodynamics in the pathophysiology of
      OSA and could predict the outcome of surgeries for airway modification in OSA
      patients.

PMID- 17029513
TI  - Linear and angular filipino cephalometric norms according to age and sex.
AB  - OBJECTIVE: To quantify relevant cephalometric parameters for Filipinos according
      to age and sex. MATERIALS AND METHODS: A total of 157 Filipino subjects (78
      males, 79 females) who fulfilled specific criteria were selected from elementary,
      high school, and college students affiliated with Manila Central University. They
      were divided into comparison groups (GI, GII, GIII, and GIV) on the basis of
      chronological age and sex. Lateral cephalograms were taken for all subjects, and
      the mean and standard deviation for each parameter was recorded and compared
      among groups. RESULTS: The male group had a longer anterior cranial base (S-N),
      total facial height (N-Me), longer lower anterior facial height (N-ANS), longer
      ramus height (Cd-Go), longer lower posterior dentoalveolar height (Mo-Mi'), and
      total mandibular length (Gn-Cd) than the female group. All these linear
      measurements were statistically significantly different between males and females
      in GI, GIII, and GIV. On the other hand, SNB angle showed significant differences
      (P = .0271) in GIV only. In the lower third of the face, significant opposite
      tendencies were found in GIV. The female group showed a clockwise rotation,
      whereas the male counterpart had a counterclockwise rotation of the mandibular
      plane. The denture pattern of both groups was characterized by a proclination of
      both lower incisor (Ii to MP) and upper incisor (Is to SN). CONCLUSIONS:
      Convexity due to dentoalveolar protrusion is the naturally occurring facial
      profile for Filipinos. The adult females showed steeper mandibular and occlusal
      plane angles than the male samples.

PMID- 17029514
TI  - Spectrum and management of dentofacial deformities in a multiethnic Asian
      population.
AB  - OBJECTIVE: The aim of this retrospective study is to investigate the spectrum and
      management of dentofacial deformities in a multiethnic Asian community. MATERIALS
      AND METHODS: Over a period of 3 years (2001 to 2003), 212 patients with
      dentofacial deformities who had undergone orthognathic surgery in a national
      tertiary specialist center in Singapore were reviewed. Patients with cleft lip
      and palate or syndromes were excluded. RESULTS: The mean age (range: 16 to 58
      years) of the patients was 24.0 years (SD 6.4) and the ratio of female to male
      was 1.3:1. The predominant ethnic group was Chinese (91.5%). The majority of the
      patients had skeletal Class III pattern (68%). Asymmetry was diagnosed in 36% of
      all cases and in 48% of skeletal Class III cases. Vertical maxillary excess was
      diagnosed in 21% of all cases and in 47% of skeletal Class II cases. Bimaxillary
      surgery involving LeFort and bilateral sagittal split osteotomies was performed
      in 84% of skeletal Class III cases and in 73% of all cases. Segmental osteotomy
      and genioplasty were performed in 41% of the cases. CONCLUSIONS: The findings
      suggest that the majority of the patients were young Chinese adults with two-jaw
      deformities requiring bimaxillary surgeries with genioplasty or segmental
      osteotomy. This finding may reflect the greater severity of dentofacial
      deformities in patients in the Asian community.

PMID- 17029515
TI  - Midfacial morphology in adult unoperated complete unilateral cleft lip and palate
      patients.
AB  - OBJECTIVE: To examine lateral cephalometric radiographs of adult unoperated cleft
      lip and palate patients for the purpose of clarifying whether maxillary
      deficiencies observed in treated cleft patients result from intrinsic defects or
      surgical intervention early in life. MATERIALS AND METHODS: This retrospective
      study examined lateral cephalograms of 30 adult patients with nonsyndromic
      complete unilateral cleft lip and palate (CUCLP). The lateral cephalograms were
      traced and evaluated for size and position of the cranial base, maxilla,
      maxillary dentition, mandible, and mandibular dentition as well as for vertical
      relationships. Comparisons with 30 adult noncleft individuals were made. RESULTS:
      In unoperated adult cleft lip and palate patients, the cranial base angle was
      increased with the anterior cranial base reduced in length. The maxilla was found
      to be normal in size and somewhat prognathic in position. Both the maxillary and
      mandibular incisors were relatively upright. The mandible was smaller in size and
      posteriorly positioned. CONCLUSIONS: The potential for normal growth of the
      maxilla exists in patients with CUCLP. It is likely that disturbances of
      maxillary growth in surgically operated cleft patients are related primarily to
      the surgical intervention.

PMID- 17029516
TI  - Occlusal development in children of African American descent. Types of terminal
      plane relationships in the primary dentition.
AB  - OBJECTIVE: To compare the types and depths of the terminal plane relationships
      (mesial step, distal step, and flush) in the primary dentitions of African
      American (AA) and European (E) children. MATERIALS AND METHODS: A convenience
      sample of 189 African American children (103 males and 86 females) was compared
      to a historical sample of 61 European children (39 males and 22 females, age
      range 2.1 to 5.2 years, mean age of 4.1 years). Plaster dental casts were
      analyzed for both samples. Terminal plane depth (TPD) was defined as the
      anteroposterior distance (APD) between the distal surfaces of the maxillary and
      mandibular second primary molars of dental casts registered in centric occlusion.
      Sample differences were evaluated using a 2-sample independent group t-test.
      RESULTS: Eighty-nine percent of African American children and 63% of European
      children exhibited a mesial step terminal plane. The average APD of the mesial
      step in African American children was 1.29 mm compared to 1.13 mm in European
      children, but this was not statistically significant (P = .18). The samples
      differed significantly (P = .001) in the average APD distal step relationship
      (AA, 1.08 mm vs E, 2.26 mm). The prevalence of distal step relationships was
      lower in African American children (5%) compared to European children (16%).
      African American children had a lower prevalence of flush terminal plane (6%)
      compared to European children (21%). CONCLUSIONS: In African American children as
      in European children, a mesial step, rather than a flush terminal plane, is the
      norm for the completed primary dentition.

PMID- 17029517
TI  - Comparison of Doppler sonography to magnetic resonance imaging and clinical
      examination for disc displacement.
AB  - OBJECTIVE: To compare electronic devices advocated as an aid in the diagnosis of
      disc displacement (DD) of the temporomandibular joint. MATERIALS AND METHODS:
      Ninety-five joints (48 subjects, 36 females and 12 males, mean age = 33.3 years,
      SD +/- 11.9) were evaluated in this study using magnetic resonance imaging (MRI),
      clinical examination, and Doppler sonography. All subjects had bilateral MRI
      scans in the sagittal closed and opened and coronal closed positions. RESULTS:
      When the clinical and the Doppler diagnoses for all subjects were compared with
      the MRI diagnosis, there was a sensitivity of 73% and 90% and a specificity of
      70% and 49%, respectively. When the clinical and the Doppler diagnoses for
      asymptomatic volunteers were compared with the MRI, there was a sensitivity of 0%
      and 100% and a specificity of 100% and 56%, respectively. For the symptomatic
      patients, there was a sensitivity of 80% and 89% and a specificity of 48% and
      45%, respectively. CONCLUSIONS: The relatively low number of false-negative
      examinations suggests that Doppler is useful for ruling out DD and may be
      especially useful in symptomatic patients. Unfortunately, the specificity was
      low, producing many false-positive examinations.

PMID- 17029518
TI  - Interleukine-1beta and tumor necrosis factor-alpha levels in the human gingival
      sulcus during orthodontic treatment.
AB  - OBJECTIVE: To test whether interleukine 1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha) levels differ from each other in different treatment
      levels. MATERIALS AND METHODS: Eighteen patients, nine female and nine male (aged
      16-19 years; mean 17.4 +/- 1.8 years), participated in this study. Each subject
      underwent a session on professional oral hygiene and received oral hygiene
      instructions. Two months later, a fixed orthodontic appliance was placed. The
      patients were seen at baseline, at days 7 and 21 and at the 3rd and 6th month as
      the leveling of the teeth occurred. Records of the baseline scores for the
      distalization forces were taken at the 6th month. Days 7 and 21 after 6 months of
      treatment were also recorded. RESULTS: There were increases in the volume of
      gingival crevicular fluid (GCF) and in the concentrations of IL-1beta and TNF
      alpha. CONCLUSIONS: Leveling and distalization of the teeth evoke increases in
      both the IL-1 and TNF-alpha levels that can be detected in GCF.

PMID- 17029519
TI  - Orthodontic bonding with varying curing time and light power using an argon
      laser.
AB  - OBJECTIVE: To test the effects of curing time and light intensity on the shear
      bond strength of adhesive composites for stainless-steel orthodontic brackets.
      MATERIALS AND METHODS: An argon laser at four different power settings (100, 150,
      200, and 250 mW) and four different exposure times (5, 10, 15, and 20 seconds)
      was used to bond adhesive-precoated (APC) stainless-steel incisor brackets to the
      facial surfaces of 154 bovine incisors. The shear bond strength of each specimen
      in 16 randomly divided groups was randomly tested to failure using an Instron
      universal testing machine. Each mode of failure was described using the adhesive
      remnant index (ARI). RESULTS: The ARI scoring system showed that the location of
      bond failure did not differ significantly in relation to exposure time (P = .40).
      However, the location of bond failure was significantly different in relation to
      light power (P = .03). CONCLUSIONS: A short exposure time and a low power setting
      produce shear bond strengths equivalent to those produced by longer exposure
      times and higher power settings.

PMID- 17029520
TI  - Fluoride-releasing adhesive and antimicrobial self-etching primer effects on
      shear bond strength of orthodontic brackets.
AB  - OBJECTIVE: To determine whether the combination of a new antimicrobial primer and
      a fluoride-releasing adhesive will affect the shear bond strength (SBS) and the
      bracket/adhesive failure mode. MATERIALS AND METHODS: A total of 120 extracted
      human teeth were randomly divided into three groups of 40 specimens each (20
      incisors, 20 premolars). Transbond XT was used in group 1, a fluoride-releasing
      adhesive (Kurasper F) was used in group 2, and a new antimicrobial self-etching
      primer (Clearfil Protect Bond) was applied in combination with Kurasper F in
      group 3. A universal testing machine was used to determine the SBS, and the
      adhesive remaining after debonding was assessed. RESULTS: No enamel fractures
      were detected in any of the specimens. SBS values for incisors and premolars were
      11.40 +/- 4.65 MPa and 10.37 +/- 3.36 MPa in group 1, 14.50 +/- 4.22 MPa and
      13.06 +/- 5.13 MPa in group 2, and 14.79 +/- 4.10 MPa and 14.60 +/- 3.55 MPa in
      group 3. Statistically significant difference (P = .001) was found in the
      premolars in group 3 revealing the highest mean SBS. Significantly lower adhesive
      remnant index (ARI) values (median ARI value of 1) were detected in group 3 when
      compared with groups 1 and 2. CONCLUSIONS: Considering the acceptable bond
      strength and the mode of failure, the combination of the new antimicrobial primer
      with the fluoride-releasing adhesive is recommended for clinical use.

PMID- 17029521
TI  - Shear bond strength of metal brackets on enamel.
AB  - OBJECTIVE: To compare the shear bond strength of different metal orthodontic
      brackets. MATERIALS AND METHODS: Five types of orthodontic metal brackets were
      selected (S1, Victory Series, 3M Unitek, Monrovia, Calif; S2, Mini Dyna-Lock, 3M
      Unitek; S3, Mini Sprint, Forestadent, Pforzheim, Germany; S4, Topic, Dentaurum,
      Inspringen, Germany; and S5, equilibrium 2, Dentaurum). Brackets were bonded on
      enamel surfaces of bovine incisors (Transbond XT, 3M Unitek) and were tested for
      shear bond strength with an Instron universal testing machine (Instron Corp,
      Canton, Mass). Data obtained in newtons and megapascals were analyzed with
      descriptive statistics and with analysis of variance and Tukey honestly
      significant difference (HSD) tests. The adhesive fracture site was classified
      with the adhesive remnant index (ARI). RESULTS: All the specimens tested had
      shear bond strength adequate to resist orthodontic forces. S5 showed
      significantly greater bond strength when compared with the other samples, except
      for S1. S1, S3, and S5 showed a significantly greater bonding force. The ARI
      index demonstrated a large variability. Retentive structure of S1, S3, and S5 had
      equal validity. The enlargement of the retentive surface enhances adhesion but
      affects the adaptability to surface irregularity of the enamel, increasing the
      risk of fracture at the interface with the bracket. CONCLUSIONS: The results of
      this study suggest that probably the retentive base extension can be lower than 7
      mm2 proposed in previous studies as the minimal area.

PMID- 17029522
TI  - Effects of silica coating and silane surface conditioning on the bond strength of
      metal and ceramic brackets to enamel.
AB  - OBJECTIVE: To evaluate the effect of tribochemical silica coating and silane
      surface conditioning on the bond strength of metal and ceramic brackets bonded to
      enamel surfaces with light-cured composite resin. MATERIALS AND METHODS: Twenty
      metal and 20 ceramic brackets were divided into four groups (n = 10 for each
      group). The specimens were randomly assigned to one of the following treatment
      conditions of the metal and ceramic brackets' surface: (1) tribochemical silica
      coating combined with silane and (2) no treatment. Brackets were bonded to the
      enamel surface on the labial and lingual sides of human maxillary premolars (20
      total) with a light-polymerized resin composite. All specimens were stored in
      water for 1 week at 37 degrees C and then thermocycled (5000 cycles, 5 degrees C
      to 55 degrees C, 30 seconds). The shear bond strength values were measured on a
      universal testing machine. Student's t-test was used to compare the data (alpha =
      0.05). The types of failures were observed using a stereomicroscope. RESULTS:
      Metal and ceramic brackets treated with silica coating with silanization had
      significantly greater bond strength values (metal brackets: 14.2 +/- 1.7 MPa, P <
      .01; ceramic brackets: 25.9 +/- 4.4 MPa, P < .0001) than the control groups
      (metal brackets: 11.9 +/- 1.3 MPa; ceramic brackets: 15.6 +/- 4.2 MPa). Treated
      specimens of metal and ceramic exhibited cohesive failures in resin and adhesive
      failures at the enamel-adhesive interface, whereas control specimens showed mixed
      types of failures. CONCLUSIONS: Silica coating with aluminum trioxide particles
      coated with silica followed by silanization gave higher bond strengths in both
      metal and ceramic brackets than in the control group.

PMID- 17029523
TI  - Six-month bracket survival with a self-etch adhesive.
AB  - OBJECTIVE: To evaluate, over a 6-month period, the clinical performance of a self
      etch adhesive (Transbond Plus Self-Etching) compared with a conventional adhesive
      that uses the etch and rinse approach (Transbond XT). MATERIALS AND METHODS: One
      operator, using the straight-wire technique, placed 567 metallic brackets in 30
      patients (age range 12-18 years) such that homologous teeth from the same arch
      received different materials. The brackets were bonded following the
      manufacturer's instruction except for the fact that the self-etch system was
      brushed for a longer time than recommended (10-15 seconds). The failure modes
      were visually classified into three modes: adhesive-enamel, adhesive-bracket, and
      cohesive failure. The survival rate of the brackets was estimated by Kaplan-Meier
      and log-rank test (P < .05). RESULTS: The failure rates of the conventional and
      self-etch [corrected] adhesives were 10.6% and 7.4%, respectively. The failure
      rate of the conventional system was 0.43 [corrected] times greater than that of
      the self-etch system. The self-etch adhesive showed a higher survival rate
      compared with the conventional system (P < .05). Most of the failures were
      cohesive and at the adhesive-enamel surface. No difference in the fracture
      debonding mode was observed for the materials. CONCLUSIONS: These findings
      indicate that the self-etch Transbond Plus Self-Etching can be safely used for
      orthodontic brackets because it provides higher survival rates than does the
      conventional Transbond XT.

PMID- 17029524
TI  - Quantitative determination of adhesion patterns of cariogenic streptococci to
      various orthodontic adhesives.
AB  - OBJECTIVE: To investigate the adhesion of various cariogenic streptococci to
      orthodontic adhesives. MATERIALS AND METHODS: Five light-cure orthodontic
      adhesives (one fluoride-releasing composite, three non-fluoride-releasing
      composites, and one resin-modified glass ionomer cement) were used. The adhesive
      type, bacterial strain, incubation time, and saliva coating were studied. Thirty
      specimens of each adhesive were incubated with unstimulated whole saliva or
      phosphate-buffered saline for 2 hours. Binding assays were then performed by
      incubating tritium-labeled streptococci with the adhesives for 3 or 6 hours.
      RESULTS: The results showed a characteristic adhesion pattern according to the
      type of bacterial strains used. Streptococcus mutans LM7 showed the highest
      amount of adhesion, whereas S sobrinus B13 showed the lowest amount of adhesion.
      The cariogenic streptococci adhered to the glass ionomer significantly more than
      to the composites, whereas there was no significant difference in the adhesion
      amount among the four composites. The extended incubation time significantly
      increased bacterial adhesion. However, saliva coating did not significantly alter
      adhesion patterns of cariogenic streptococci. CONCLUSIONS: This study suggests
      that cariogenic streptococci can adhere diversely according to adhesive type and
      that the adhesion of the cariogenic streptococci is not influenced by its
      fluoride-releasing properties.

PMID- 17029525
TI  - Uprighting partially impacted permanent second molars.
AB  - Impaction of the lower second molar is not a common problem, but it is very
      challenging for both orthodontist and oral surgeon. Treatment options depend on
      the degree of tooth inclination, the position of the third molars, and the
      desired type of movement, which may be surgical and/or orthodontic in nature. A
      good treatment alternative is surgical uncovering with orthodontically-assisted
      eruption. A case of successful uprighting using a 0.017 x 0.025-inch titanium
      molybdenum alloy (TMA) tip-back cantilever is presented. Different aspects of
      uprighting impacted second molars are discussed in light of the literature. The
      iatrogenic character of lower second molar impaction is emphasized.

PMID- 17029526
TI  - Cephalometric facial soft tissue changes with the twin block appliance in Class
      II division 1 malocclusion patients. A systematic review.
AB  - OBJECTIVE: To evaluate facial soft tissue changes after the use of the twin block
      appliance in Class II division 1 malocclusion patients. MATERIALS AND METHODS:
      Several electronic databases (PubMed, MEDLINE, MEDLINE In-Process & Other Non
      Indexed Citations, Cochrane databases, EMBASE, Web of Science, and LILACS) were
      searched with the help of a senior health-sciences librarian. Abstracts that
      appeared to fulfill the initial selection criteria were selected by consensus,
      and the original articles were retrieved. The article references were hand
      searched for possible missing articles. Clinical trials that assessed facial soft
      tissue changes with the use of the twin block appliance without any surgical
      intervention or syndromic characteristics were considered. A comparable untreated
      control group was required to factor out normal growth changes. RESULTS: Two
      articles fulfilled the selection criteria and quantified facial soft tissue
      changes. Although some statistically significant changes in the soft tissue
      profile were found, the magnitude of the changes may not be perceived as
      clinically significant. Changes produced in the upper lip seem to be
      controversial, although the study with sounder methodological quality did not
      report significant changes. No change in the anteroposterior position of the
      lower lip and the soft tissue menton or improvement of the facial convexity was
      found. CONCLUSIONS: Three-dimensional quantification of the soft tissue changes
      is required to overcome current limitations in our understanding of the soft
      tissue changes obtained after the use of the twin block appliance in Class II
      division 1 malocclusion patients.

PMID- 17029527
TI  - Lower incisor retraction with a modified corticotomy.
AB  - This case report demonstrates the orthodontic treatment facilitated with a new
      conservative corticotomy technique to shorten the treatment time during lower
      incisor retraction. The patient was a 22-year-old woman with protrusive profile,
      severe anterior crowding, an anterior crossbite, and Class III dental
      relationship. Orthodontic treatment consisted of the extraction of four first
      premolars with maximum anchorage. A modified corticotomy technique, in which the
      lingual vertical and subapical horizontal cuts were eliminated, was combined with
      orthodontic therapy for the retraction of the lower anterior teeth. Corticotomy
      facilitated orthodontics dramatically reduced the treatment time without any
      adverse effects on the periodontium and the vitality of the teeth. The main
      advantages of this modified corticotomy technique were the elimination of the
      lingual cuts and flap, the reduction of surgery time, and minimum discomfort to
      the patient. At the end of active orthodontic therapy, balanced occlusion and
      facial esthetics were achieved.

PMID- 17029528
TI  - Familial occurrence of nonsyndromal multiple supernumerary teeth. A rare
      condition.
AB  - The occurrence of multiple supernumerary teeth is a rare phenomenon and is often
      found in association with syndromes such as cleidocranial dysplasia, Gardners
      syndrome, or cleft lip and palate. Only a few examples of nonsyndromal multiple
      supernumerary teeth have been reported in the literature. There is a predilection
      for the mandible and in the premolar area followed by the molar and anterior
      regions. This article reports the presence of nonsyndromal multiple supernumerary
      teeth involving both jaws in children and in their mothers. The clinical and
      radiographic appearance of the anomalies and treatment modalities are discussed.

PMID- 17029529
TI  - Skeletal characteristics and treatment outcome of five patients with Robin
      sequence.
AB  - OBJECTIVE: To examine the variation in the precise skeletal characteristics and
      the treatment outcomes of five Japanese Robin sequence cases. MATERIALS AND
      METHODS: The birth histories and orthodontic records of five Japanese Robin
      sequence patients were collected and analyzed. RESULTS: All cases had a
      retrognathic appearance with small SNA and SNB angles. They had significantly
      steep mandibular planes with lingual tipped incisors in both arches. The gonial
      angles in two cases were within the Japanese norm, whereas the remaining three
      showed significantly enlarged angles. Moreover, all cases showed a significantly
      shorter ramus length, but the mandibular body was short in only two cases. All
      had moderate or severe crowding in both arches, and therefore extraction of
      lateral dentition or lateral incisors was performed in conjunction with
      orthodontic treatment. An edgewise multibracket appliance was placed, and labial
      tipping of the lower incisors was performed in all cases. All obtained normal
      functional occlusion after active treatment, but the retrognathic appearance
      remained in most cases. CONCLUSIONS: The present cases with Robin sequence showed
      variation in the gonial angle and mandibular body length, although all commonly
      exhibited smaller SNA and SNB angles with significantly steep mandibular planes.
      Significant labial tipping of the lower incisors was required during the active
      treatment, and all cases finally obtained functional occlusion, indicating the
      relatively good prognosis on the occlusion of this sequence.

PMID- 17029530
TI  - Condylar asymmetry in bilateral posterior crossbite patients.
AB  - OBJECTIVE: To investigate whether patients with bilateral posterior crossbite
      have asymmetrically developed condyles. MATERIALS AND METHODS: The study group
      consisted of 75 patients with bilateral posterior crossbite, and a control group
      of 75 subjects with normal occlusion. Condylar, ramal, and condylar plus ramal
      asymmetry values were computed for all of the subjects on orthopantomograms. Data
      were analyzed statistically by means of paired t-test and Student's t-test.
      RESULTS: The patients with bilateral posterior crossbite had more asymmetrical
      condyles relative to the controls. However, there were no statistically
      significant differences in condylar, ramal, or condylar plus ramal heights
      between left and right sides in both the control and crossbite groups.
      CONCLUSION: Patients with bilateral posterior crossbite can have asymmetrical
      condyles and might be at risk for the development of future skeletal mandibular
      asymmetries.

PMID- 17029531
TI  - Microscrew anchorage in skeletal anterior open-bite treatment.
AB  - OBJECTIVE: To evaluate the effectiveness of miniscrew anchorage for intrusion of
      the posterior dentoalveolar region to correct skeletal open bite. MATERIALS AND
      METHODS: The study was comprised of 12 patients (aged 14.3 to 27.2 years; mean
      18.7 years) with anterior open bites. All the patients presented a Class II
      skeletal pattern and excessive posterior growth. Self-drilling miniscrew implants
      were inserted into the posterior midpalatal area and the buccal alveolar bone
      between the lower molars. A transpalatal and a lingual arch were used to maintain
      the molars on each side in order to avoid overrotation during intrusion. A force
      of 150 g was applied to the microscrews on each side to intrude the posterior
      teeth. Lateral cephalograms of all 12 patients were taken preintrusion and
      immediately after completion of the intrusion. The cephalometric films were
      measured and compared. RESULTS: The results showed that the anterior open bites
      in 12 patients were all corrected in a mean of 6.8 months. Overbite increased by
      a mean of 4.2 mm (P < .001), from -2.2 mm in preintrusion to 2.0 mm in
      postintrusion. The maxillary and mandibular first molars were intruded for an
      average of 1.8 mm (P < .001) and 1.2 mm (P < .001), respectively. The mandibular
      plane angle was reduced by 2.3 degrees (P < .001), which led to a
      counterclockwise rotation of the mandible with a significant decrease in the
      anterior facial heights (mean of 1.8 mm; P < .001). CONCLUSION: Miniscrew
      anchorage has the advantages of being a simpler procedure, being minimally
      invasive, and requiring minimal patient cooperation.

PMID- 17029532
TI  - Dental arch widths and mandibular-maxillary base width in Class III malocclusions
      with low, average and high MP-SN angles.
AB  - OBJECTIVE: To analyze the development of the dental arches and skeletal
      mandibular-maxillary bases in untreated Class III malocclusions with low averages
      and high mandibular plane angles in subjects aged 10 to 14. MATERIALS AND
      METHODS: The records of 50 untreated Japanese girls with Class III malocclusions
      at age 10 were selected from the files of patients pending orthodontic surgery.
      The patients included those with low (< or =27 degrees), average (27 degrees
      through 37 degrees) and high (>37 degrees) mandibular plane angles. The maxillary
      skeletal base width, biantegonial width, and maxillary and mandibular intermolar
      width were determined on posteroanterior cephalograms obtained at annual
      intervals when subjects were between 10 and 14 years of age. The difference
      between the maxillary and mandibular intermolar width was also calculated and
      reported. RESULTS: All skeletal and dental transverse widths in the high-angle
      group were significantly smaller than those in the low-angle group (P < .05) from
      ages 10 to 14. On the other hand, the maxillary to mandibular molar difference
      was the same for the three groups (P > .05) at each age. The deviations in molar
      differences did increase from age 10 to age 14 in all three groups. CONCLUSION:
      Mandibular plane angles might play a stronger role in the transverse skeletal
      growth of the maxilla and the mandible than the transverse dental growth of the
      maxilla and the mandible.

PMID- 17029533
TI  - Long-term stability of orthodontic treatment and patient satisfaction. A
      systematic review.
AB  - OBJECTIVE: To evaluate morphologic stability and patient satisfaction at least 5
      years after orthodontic treatment. MATERIALS AND METHODS: Published literature
      was searched through the PubMed and Cochrane Library electronic databases from
      1966 to January 2005. The search was performed by an information specialist at
      the Swedish Council on Technology Assessment in Health Care. The inclusion
      criteria consisted of a follow-up period of at least 5 years postretention;
      randomized clinical trials, prospective or retrospective clinical controlled
      studies, and cohort studies; and orthodontic treatment including fixed or
      removable appliances, selective grinding, or extractions. Two reviewers extracted
      the data independently and also assessed the quality of the studies. RESULTS: The
      search strategy resulted in 1004 abstracts or full-text articles, of which 38 met
      the inclusion criteria. Treatment of crowding resulted in successful dental
      alignment. However, the mandibular arch length and width gradually decreased, and
      crowding of the lower anterior teeth reoccurred postretention. This condition was
      unpredictable at the individual level (limited evidence). Treatment of Angle
      Class II division 1 malocclusion with Herbst appliance normalized the occlusion.
      Relapse occurred but could not be predicted at the individual level (limited
      evidence). The scientific evidence was insufficient for conclusions on treatment
      of cross-bite, Angle Class III, open bite, and various other malocclusions as
      well as on patient satisfaction in a long-term perspective. CONCLUSIONS: This
      review has exposed the difficulties in drawing meaningful evidence-based
      conclusions often because of the inherent problems of retrospective and
      uncontrolled study design.

PMID- 17029534
TI  - Effects of self-etching primer on shear bond strength of orthodontic brackets at
      different debond times.
AB  - OBJECTIVE: To evaluate the effect of a self-etching primer on shear bond
      strengths (SBS) at the different debond times of 5, 15, 30, and 60 minutes and 24
      hours. MATERIALS AND METHODS: Brackets were bonded to human premolars with
      different etching protocols. In the control group (conventional method [CM])
      teeth were etched with 37% phosphoric acid. In the study group, a self-etching
      primer (SEP; Transbond Plus Self Etching Primer; 3M Unitek, Monrovia, Calif) was
      applied as recommended by the manufacturer. Brackets were bonded with light-cure
      adhesive paste (Transbond XT; 3M Unitek) and light-cured for 20 seconds in both
      groups. The shear bond test was performed at the different debond times of 5, 15,
      30 and 60 minutes and 24 hours. RESULTS: Lowest SBS was attained with a debond
      time of 5 minutes for the CM group (9.51 MPa) and the SEP group (8.97 MPa).
      Highest SBS was obtained with a debond time of 24 hours for the CM group (16.82
      MPa) and the SEP group (19.11 MPa). Statistically significant differences between
      the two groups were not observed for debond times of 5, 15, 30, or 60 minutes.
      However, the SBS values obtained at 24 hours were significantly different (P <
      .001). CONCLUSIONS: Adequate SBS was obtained with self-etching primer during the
      first 60 minutes (5, 15, 30 and 60 minutes) when compared with the conventional
      method. It is reliable to load the bracket 5 minutes after bonding using self
      etching primer (Transbond Plus) with the light-cure adhesive (Transbond XT).

PMID- 17029535
TI  - Maxillary canine--first premolar transposition.
AB  - Tooth transpositions present at a relatively low incidence in the world
      population and primarily affect maxillary canines and premolars. Treatment of
      this disturbance should take into account aspects such as facial pattern, age,
      malocclusion, tooth-size discrepancy, stage of eruption, and magnitude of the
      transposition. Mechanics for correction should be entirely individualized,
      reducing the risks and adverse effects. Practitioners often select simpler
      options, indicating extraction of permanent teeth, which is an irreversible
      procedure that may bring about damages to the patient. This study presents a case
      report and treatment of unilateral transposition of maxillary canine and premolar
      with repositioning of affected teeth to their respective normal positions.

PMID- 17029536
TI  - Unusual extraction treatment in Class II division 1 using C-orthodontic mini
      implants.
AB  - This paper describes the treatment of a female patient, aged 23 years and 5
      months, with a Class II division 1 malocclusion, who showed severe anterior
      protrusion and lower anterior crowding. Specially-designed orthodontic mini
      implants were placed bilaterally in the interdental space between both the upper
      and the lower posterior teeth. Both lower first molars showed severe apical
      lesions. Therefore, the treatment plan consisted of extraction of both upper
      first premolars and lower first molars, en masse retraction of the upper six
      anterior teeth, lower anterior alignment, and protraction of all the lower
      molars. C-implants(R) were used as substitutes for maxillary posterior anchorage
      teeth during anterior retraction and as hooks for mandibular molar protraction.
      The correct overbite and overjet were obtained by intruding and retracting the
      upper six anterior teeth into their proper positions. The dentition was detailed
      using conventional orthodontic appliances. The upper C-implants contributed to an
      improvement in facial balance, and the lower C-implants made it possible to
      protract the lower second and third molars with less effect on the axis of the
      lower anterior teeth. The active treatment period was 29 months and the patient's
      teeth continued to be stable 11 months after debonding.

PMID- 17029537
TI  - Mesial migration effect on root morphology of mandibular third molars.
AB  - OBJECTIVE: To test the hypothesis that there is a relationship between forward
      mandibular third molar migration and root curvature of the mandibular third
      molars. MATERIALS AND METHODS: The study is comprised of 64 patients who had a
      history of unilateral mandibular first molar extraction before 16 years of age
      with no other missing teeth or prosthetic restorations in the mandible. The
      extraction space was fully or partly closed. The mean remaining space was 1.1 +/-
      0.41 mm. The root angles for the mesial and distal roots of the mandibular third
      molars were measured on the panoramic radiographs by calculating the differences
      between the angle formed by the long axis drawn perpendicular to the occlusal
      plane of the crown of mandibular third molar and the central line of the lower
      one ninth of the root through the root apex. The differences between the
      extracted and nonextracted sides for mesial and distal roots were analyzed using
      a paired sample t-test. RESULTS: Both mesial and distal roots were approximately
      8 degrees more vertical on the extraction sides than on the nonextraction sides.
      The differences were statistically significant. CONCLUSION: Mesial tooth
      migration of mandibular third molars reduces the amount of root curvature
      developing on this tooth.

PMID- 17029538
TI  - Chinese norms of McNamara's cephalometric analysis.
AB  - OBJECTIVE: To establish cephalometric norms of McNamara's analysis in young
      Chinese and compare them to those of a matched young Caucasian sample. MATERIALS
      AND METHODS: The material comprised lateral cephalometric radiographs of a random
      sample of 200 male and 205 female 12-year-old southern Chinese children, and an
      additional sample of 43 male and 43 female 12-year-old British Caucasian children
      in Hong Kong. The radiographs were digitized twice with the CASSOS program.
      RESULTS: The results showed that there were statistically significant gender
      differences for six out of the 11 cephalometric variables in the Chinese, but for
      only one variable in the Caucasians. The size of the statistically significant
      gender differences varied from -0.3 to 0.4 on SD scores. There were statistically
      significant ethnic differences for eight variables in males and seven variables
      in females. The size of the observed statistically significant ethnic differences
      varied from -1.8 to 1.6 on SD scores. CONCLUSION: The use of specific standards
      for Chinese, separate for gender, for McNamara's cephalometric analysis seems to
      be justified.

PMID- 17029539
TI  - Perceptions of orthognathic surgery patient's change in profile. A five-year
      follow-up.
AB  - OBJECTIVES: To compare pairs of silhouettes generated from presurgical and 5-year
      postsurgical cephalometric radiographs to evaluate whether orthodontists, oral
      surgeons, and lay persons perceive changes in profile resulting from orthodontics
      and mandibular advancement surgical treatment. MATERIALS AND METHODS: A survey
      based method of data collection was used to evaluate 15 pairs of silhouettes.
      These silhouettes included 1 control pair and 14 surgically treated pairs
      representing mandibular advancements ranging from 0.11 mm to 10.13 mm. Collected
      data were analyzed to determine whether changes can be perceived and whether
      these changes were esthetically pleasing. RESULTS: The control silhouette pair
      was identified by 104 of 127 evaluators. For the 14 surgical treated silhouette
      pairs, the vast majority of evaluators (N = 127; 53 orthodontists, 32 oral
      surgeons, and 42 lay persons) were able to identify changes in profile and
      individual features. At least one group of evaluators was able to perceive
      significant (P < .05) improvement in the visual analog scale (VAS) score for all
      these silhouette pairs, except for the pair with 10.13 mm of mandibular
      advancement. This silhouette pair, which represented the largest mandibular
      advancement, was perceived to have a significant (P < .05) worsening in the VAS
      score by the lay person group. There were significant differences among the
      groups of evaluators. Esthetic improvement in profile was perceived for 13 of 14
      surgically treated silhouette pairs. CONCLUSION: In some cases, orthodontists,
      oral surgeons, and lay persons perceived changes in profile differently.

PMID- 17029540
TI  - Apoptosis of growth plate chondrocytes occurs through a mitochondrial pathway.
AB  - OBJECTIVE: To determine the role of mitochondria in chondrocyte apoptosis induced
      by inorganic phosphate (Pi). MATERIALS AND METHODS: Chondrocytes isolated from
      the growth plates of chick embryo tibia were treated with Pi in serum-free media;
      chondrocyte viability, mitochondrial membrane potential, cytochrome c release
      from mitochondria, caspase 3 activity, endonuclease activity, and DNA
      fragmentation were investigated. RESULTS: Exposure to Pi for 24 hours induced
      apoptosis in growth plate chondrocytes through a pathway that involved loss of
      mitochondrial function, release of cytochrome c into the cytoplasm, increases in
      caspase 3 and endonuclease activities, and fragmentation of DNA. CONCLUSIONS:
      This study suggests that mitochondria are important players in Pi-induced
      apoptosis.

PMID- 17029541
TI  - Friction of conventional and silica-insert ceramic brackets in various bracket
      wire combinations.
AB  - OBJECTIVE: To compare the level of friction resistance (FR) of conventional and
      silica-insert ceramic brackets using various bracket-wire combinations and
      angulations. MATERIALS AND METHODS: Four types of ceramic brackets were examined:
      (1) polycrystalline alumina bracket (PCA-C), (2) polycrystalline alumina bracket
      with a stainless steel (SS) slot (PCA-M), (3) polycrystalline alumina bracket
      with a silica layer (PCA-S), and (4) monocrystalline sapphire bracket (MCS). A
      conventional SS bracket was used as the control. The static and kinetic FR in
      four bracket-wire angulations (0 degrees, 5 degrees, 10 degrees, and 15 degrees)
      was examined using SS and beta-titanium (beta-Ti) orthodontic wires, 0.019 x
      0.025 inches in size, under elastic ligature in the dry state. RESULTS: The FR
      generated by the PCA-S bracket was significantly lower than that generated with
      the other ceramic brackets, and was similar to that of the SS bracket. The PCA-S
      bracket showed the lowest FR with both the SS and the beta-Ti wires at zero
      bracket angulation. The FR to sliding increased rapidly and nonlinearly when the
      bracket wire angulation was >5 degrees. The PCS-S bracket showed the lowest FR
      from 5 degrees to 15 degrees of angulation. The MCS bracket demonstrated the
      highest increase in FR from 0 degrees to 15 degrees of angulation, showing the
      highest FR at 15 degrees of angulation. CONCLUSION: PCA-S showed minimal FR among
      the ceramic brackets, and was comparable to the conventional SS bracket. The
      silica layer and rounded edges of the ceramic slot lowered FR considerably.

PMID- 17029542
TI  - Three cements used for orthodontic banding of porcelain molars.
AB  - OBJECTIVE: Objectives of this study were to (1) compare the mean shear-peel bond
      strength of orthodontic bands luted to porcelain molar denture teeth with glass
      ionomer cement (GIC), resin-modified glass ionomer cement (RMGIC), or compomer
      cement; (2) assess the amount of cement remaining on the teeth after debanding;
      and (3) compare the survival times of the cemented bands subject to mechanical
      fatigue. MATERIALS AND METHODS: Sixty banded denture teeth (20 per cement group)
      were used to determine shear-peel bond strength, and 30 banded denture teeth (10
      per cement group) were used to determine fatigue survival time. Shear-peel bond
      strength was determined with a universal testing machine, and groups were
      compared by one-way analysis of variance. The amount of cement remaining on the
      teeth after band removal was scored, and a chi-square test was used to compare
      groups. Fatigue testing was conducted in a ball mill, and a log-rank test was
      used to compare differences in survival times. RESULTS: No differences were found
      in mean shear-peel bond strength among the three groups. The amount of cement
      remaining on the teeth varied between the compomer and GIC groups (P = .01), with
      more compomer cement remaining relative to GIC. The mean survival times of bands
      cemented with compomer or RMGIC were longer than for bands cemented with GIC (P <
      .001). CONCLUSION: The findings show that on porcelain teeth the band cements
      have comparable mean shear-peel bond strengths, but that band retention with
      RMGIC and compomer cement are superior to GIC when subjected to simulated
      mechanical fatigue.

PMID- 17029544
TI  - The third-order angle and the maxillary incisor's inclination to the NA line.
AB  - OBJECTIVE: To evaluate the relationship between the angular measurement data
      (incisor's long axis to NA line) and the third-order angle (TA) according to
      Andrews' description. MATERIALS AND METHODS: The materials in the study included
      the lateral radiographs and corresponding dental casts of 32 males and 35 females
      between 10 and 25 years of age, regardless of their skeletal and dental
      relationships. All subjects were white and none had undergone orthodontic
      therapy. Using lateral radiographs, upper and lower incisor angulations were
      assessed in reference to the NA line. These data were compared with third-order
      angles derived from direct dental cast measurements, which were performed using
      an incisor inclination recording appliance. RESULTS: The third-order angle
      measurements recorded from the dental casts were a mean of 16.2 degrees (SD = 5.3
      degrees) smaller than the axial inclination according to the NA line. In this
      sample, there was a range of 42.7 degrees for the TA variable (mean = 5.6
      degrees, SD = 9.73 degrees) and 47 degrees for the 1NA/deg variable (mean = 21.7
      degrees, SD = 8.67 degrees). A highly significant correlation existed (r = 0.84)
      between Andrews' angle and the inclination estimated in reference to the NA line.
      CONCLUSION: Incisor inclination can be better estimated by recognizing the
      relationship between the torque angle and the axial inclination referred to the
      NA line. Third-order measurements using dental casts can offer a simple way to
      get an objective and rapid vision of the incisor's inclination.

PMID- 17029543
TI  - Effect of enamel etching on tensile bond strength of brackets bonded in vivo with
      a resin-reinforced glass ionomer cement.
AB  - OBJECTIVE: To evaluate the influence of enamel etching on tensile bond strength
      of orthodontic brackets bonded with resin-reinforced glass ionomer cement.
      MATERIALS AND METHODS: The sample group consisted of 15 patients who had
      indications for extraction of four premolars for orthodontic reasons, equally
      divided into two different groups according to bracket and enamel preparation.
      Brackets were bonded in vivo, by the same operator, using a split mouth random
      technique: Group 1 (control), phosphoric acid + Fuji Ortho LC; Group 2, Fuji
      Ortho LC without acid conditioning. The teeth were extracted after 4 weeks using
      elevators. An Instron Universal Testing Machine was used to apply a tensile force
      directly to the enamel-bracket interface at a speed of 0.5 mm/min. The groups
      were compared using a Mann-Whitney U-test and Weibull analysis. RESULTS: Mean
      results and standard deviations (in MPa) for the groups were: Group 1, 6.26
      (3.21), Group 2, 6.52 (2.73). No significant difference was observed in the bond
      strengths of the two groups evaluated (P = .599). CONCLUSIONS: Fuji Ortho LC
      showed adequate shear bond strength and may be suitable for clinical use.

PMID- 17029545
TI  - Congenital missing permanent teeth in Korean unilateral cleft lip and alveolus
      and unilateral cleft lip and palate patients.
AB  - OBJECTIVE: To investigate the differences in the congenital missing teeth pattern
      in terms of tooth type (permanent maxillary lateral incisor [MLI] and maxillary
      second premolar [MSP]) and sidedness (cleft vs noncleft) between boys and girls
      in Korean unilateral cleft lip and alveolus (UCLA) and unilateral cleft lip and
      palate (UCLP) patients. MATERIALS AND METHODS: This study used the charts,
      models, radiographs, and intraoral photographs of 90 UCLA patients and 204 UCLP
      patients (ages 6 to 13 years). Binomial test, chi-square test, Fisher exact test,
      maximum likelihood analysis of variance, and the odds ratio were performed.
      RESULTS: According to the relationship between the congenital missing teeth
      pattern and the cleft type, the UCLP patients had 2.98 times more missing MLIs
      and 1.80 times more missing MSPs than did the UCLA patients. The MLI was
      congenitally missing more in boys than in girls, but the MSP showed the opposite
      tendency. Boys had a higher frequency of congenital missing MLIs and MSPs on the
      cleft side than did girls. However, on the noncleft side and both sides, girls
      had a higher frequency of congenital missing MLIs and MSPs than did boys. Results
      showed a gender-dominant pattern of congenital missing MLIs and MSPs. CONCLUSION:
      These results suggest that gender and cleft type might affect the congenital
      missing teeth pattern in terms of tooth type and sidedness.

PMID- 17029546
TI  - An evaluation of buccal shield treatment. A clinical and cephalometric study.
AB  - OBJECTIVE: To evaluate the short-term effects of the buccal shield modification
      of the lip-bumper design and on various mandibular dental arch parameters and to
      determine whether the changes in arch widths are due to the tipping or bodily
      movements of the teeth involved. MATERIALS AND METHODS: This study included 45
      consecutively treated patients (29 girls and 16 boys) from a private orthodontic
      practice. Student's and paired t-tests were used to test the null hypothesis of
      no change over time for the various measurements. Linear regression analyses were
      used to determine whether treatment time was a significant predictor of arch
      width expansion. Significance for all statistical tests was predetermined at P <
      or = .05. RESULTS: Student's t-test results indicated the presence of a
      significant (P < .0001) increase in all the arch parameters measured. The
      greatest mean expansion was observed at the first (5.0 +/- 2.2 mm) and second
      (3.4 +/- 2.2 mm) premolar width measurements. The changes in arch width
      parameters were significantly (P < .0001) greater than the normal age-related
      changes in the corresponding parameters. There was no significant difference
      between arch width expansion of the occlusal vs gingival levels, indicating a
      bodily and not tipping movement. Only 30% of the lower incisors demonstrated an
      increase in their proclination beyond normal values. CONCLUSION: When using the
      buccal shield appliance, the mandibular arch width parameters can be expanded in
      the mixed dentition with bodily movement of teeth. The expanded arch width
      dimensions are greater than what would be expected as a result of normal growth.

PMID- 17029547
TI  - Dentoskeletal effects and "effective" temporomandibular joint, maxilla and chin
      changes in good and bad responders to van Beek activator treatment.
AB  - OBJECTIVE: To assess possible differences in dentoskeletal effects and
      "effective" temporomandibular joint, maxilla, and chin changes between good and
      bad responders to van Beek activator treatment. MATERIALS AND METHODS: The
      subject material consisted of 20 consecutive normodivergent male Class II
      division 1 patients treated with a van Beek activator. Because of insufficient
      cooperation, four patients were excluded. Lateral head films were taken 6 months
      before treatment, at start of treatment, and after 12 months of treatment. The
      patients were placed into a good responder group (successful, n = 8) and a bad
      responder group (unsuccessful, n = 8). An overjet reduction > or =4 mm was
      considered successful. RESULTS: During the van Beek treatment period, the good
      responders showed a significantly larger improvement in overjet and molar
      relationship than did the bad responders. The good responders exhibited a
      significant posterior development of condylion, less anterior mandibular
      autorotation, retrusion of upper incisors, protrusion of lower incisors,
      distalization of maxillary molars, and a mesial movement of mandibular molars. No
      significant dental movements were seen in the bad responders. CONCLUSIONS:
      Although van Beek activator treatment affected the direction of condylar growth,
      as well as the direction of maxilla and chin changes, it can be concluded that
      skeletal changes did not contribute to the Class II correction. Instead, overjet
      reduction during van Beek activator treatment was found to be due to a favorable
      dental reaction.

PMID- 17029548
TI  - Etching enamel for orthodontics with an erbium, chromium:yttrium-scandium-gallium
      garnet laser system.
AB  - OBJECTIVE: To test the shear bond strength, surface characteristics, and fracture
      mode of brackets that are bonded to enamel etched with an erbium,
      chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser operated at different
      power outputs: 0.5 W, 1 W, and 2 W. MATERIALS AND METHODS: Human premolars that
      had been extracted for orthodontic purposes were used. Enamel was etched with an
      Er,Cr:YSGG laser system operated at one of three power outputs or with
      orthophosphoric acid. RESULTS: The shear bond strength associated with the 0.5-W
      laser irradiation was significantly less than the strengths obtained with the
      other irradiations. Both the 1-W and 2-W laser irradiations were capable of
      etching enamel in the same manner. This finding was confirmed by scanning
      electron microscopy examination. The evaluation of adhesive-remnant-index scores
      demonstrated no statistically significant difference in bond failure site among
      the groups, except for the 0.5-W laser-etched group. Generally, more adhesive was
      left on the enamel surface with laser irradiation than with acid etching.
      CONCLUSION: The mean shear bond strength and enamel surface etching obtained with
      an Er,Cr: YSGG laser (operated at 1 W or 2 W for 15 seconds) is comparable to
      that obtained with acid etching.

PMID- 17029549
TI  - Tumor necrosis factor-alpha levels during two different canine distalization
      techniques.
AB  - OBJECTIVES: To compare levels of tumor necrosis factor (TNF)-alpha while applying
      continuous and heavy interrupted forces. MATERIALS AND METHODS: A hybrid
      retractor was used in the first group. In the second group, rapid canine
      distalization through periodontal distraction was performed. Gingival crevicular
      fluid samples were collected from the distal sides of the canine teeth before
      attaching the appliances and at 1 hour, 24 hours, and 1 week after the force was
      applied. RESULTS: In the hybrid reactor group, concentration of TNF-alpha
      decreased at 1 week according to 24-hour measurements. In the rapid canine
      distalization group, it severely increased at 1 hour. In the evaluation of
      between-group differences, significantly higher values were determined in the
      rapid canine distalization group at 1 hour and 1 week. CONCLUSIONS: Heavy
      interrupted force induces a rapid release of TNF-alpha, and the tissue response
      continues for a longer time period. To avoid the harmful effects of heavy
      interrupted force, there might be feedback mechanisms that prevent the mediators
      from increasing excessively.

PMID- 17029550
TI  - Trunk inclination, pelvic tilt and pelvic rotation in relation to the
      craniofacial morphology in adults.
AB  - OBJECTIVE: To relate the differences in the posture of patients with different
      craniofacial morphologies. SUBJECTS AND METHODS: Fifty-three adult patients with
      Class II and III malformations were examined by cephalometric analysis and
      rasterstereography. The facial depth, maxillary position, mandibular plane angle,
      inner gonial angle, facial axis, and lower facial height were evaluated and
      classified into a basal distal-mesial group and a horizontal-vertical group by
      means of threshold parameters. Analyzing the results of the rasterstereography,
      the spine's lateral perpendicular deviation, the pelvic tilt, and the pelvic
      rotation were calculated by means of mathematical algorithms on the basis of the
      three-dimensional spine profile. To determine the statistically significant
      correlations between the studied parameters, the t-test was applied in groups
      with a normal distribution, and the Mann-Whitney U-test was used in the cases of
      abnormally distributed variables (significance level P < .05). RESULTS:
      Statistically significant differences (P < .05) in pelvic torsion were documented
      with respect to the facial axis and facial depth. Moreover, the differences (P <
      .05) between patients with a skeletal horizontal-vertical facial axis and
      patients with a basal distal-mesial position for the facial depth could be
      determined for the pelvic torsion. CONCLUSIONS: As a clinical consequence of the
      results, an extension of the interdisciplinary concepts within the sense of an
      orthopedic examination can be considered for patients undergoing a combined
      orthodontic-operative therapy.

PMID- 17029551
TI  - Effects of cervical headgear on overbite against the background of existing
      growth patterns. A retrospective analysis of study casts.
AB  - OBJECTIVE: To test the questions "Does cervical headgear treatment necessarily
      lead to a reduction of overbite?" and "Are there differences in treatment results
      due to different growth patterns or the initial overbite?" MATERIALS AND METHODS:
      Initial and intermediary casts of 247 patients who had been treated exclusively
      with headgear were analyzed for changes in the occlusal relationship of the first
      molars and overbite. Orthodontic treatment consisted of the application of
      cervical headgear with nonangulated external arms applied at a force of 3.5-4.0
      N. Only patients showing dental changes of occlusal relationship > or = 4 mm
      during at least a 6-month treatment duration were selected. Growth patterns were
      identified by the y-axis values measured on lateral cephalograms obtained at
      study entry. Six groups were formed on the basis of these growth patterns.
      RESULTS: Headgear treatment induced bite deepening in patients with vertical
      growth patterns and bite opening in patients with horizontal growth patterns.
      Further subdivision based on initial overbite revealed bite deepening in patients
      with small initial overbite and bite opening in patients with large initial
      overbite. These differences were statistically significant (P < .05). Only minor
      changes were observed in patients with an initial overbite of 3-4 mm.
      CONCLUSIONS: Overbite reductions were not dependent on the growth pattern.
      Orthodontists should expect bite opening in deep-bite situations and bite
      deepening in open-bite situations. However, initial overbite situations of 3-4 mm
      should not be expected to change in a significant way.

PMID- 17029552
TI  - Effects of interferon-gamma on bone remodeling during experimental tooth
      movement.
AB  - OBJECTIVE: To determine the effects of interferon-gamma (IFN-gamma) on bone
      remodeling during orthodontic tooth movement. MATERIALS AND METHODS: Thirty adult
      male Sprague Dawley rats were randomly categorized into five groups. IFN-gamma
      was administered in three different doses (0.01, 0.02, and 0.05 microg/20 microL)
      and the remaining two groups served as control. Mandibular first molars were
      moved mesially by means of Ni-Ti closed coil springs in all groups. The results
      were evaluated histomorphometrically, and parameters of trabecular bone volume
      (BV/TV), trabecular bone number (Tr.N), and trabecular separation (Tr.Sep) were
      observed at the interradicular bone area of the mandibular first molars. RESULTS:
      Increases in BV/TV and Tr.N and decreases in Tr.Sep revealed the antiosteoclastic
      activity of IFN-gamma. CONCLUSION: IFN-gamma administration may be useful
      clinically for anchorage control.

PMID- 17029553
TI  - A fused maxillary central incisor with dens evaginatus as a talon cusp.
AB  - This report presents a rare case of concurrence of dens evaginatus and dental
      fusion affecting the maxillary right upper central incisor of a 9-year-old male
      patient. An association of dens evaginatus and dental fusion within the same
      tooth is rare. In this case, an orthopantomogram, a lateral cephalogram,
      intraoral radiographs, and a magnetic resonance tomogram were made to obtain a
      proper diagnosis and to confirm the exact path of the root canals. Because of a
      forced bite, an orthodontic treatment involving cusp reduction was initiated.
      During the cusp reduction, no traumatic intraoperative exposure of pulp tissue
      occurred, and no endodontic or surgical treatment procedures were necessary.
      After a multibracket treatment, a harmonious integration of the tooth in the
      upper dental arch was achieved.

PMID- 17029554
TI  - Short-term effect of mastic gum on salivary concentrations of cariogenic bacteria
      in orthodontic patients.
AB  - OBJECTIVE: To determine antibacterial activity of chewing mastic gum against the
      salivary levels of Streptococcus mutans, the total number of viable bacteria, and
      lactobacilli in patients undergoing therapy with fixed orthodontic appliances.
      MATERIALS AND METHODS: In this study, the levels of S mutans, lactobacilli, and
      total cultivated bacteria were measured before and after chewing mastic gum. The
      antibacterial effects of chewing mastic gum against these microorganisms in
      saliva were compared with a placebo gum. The counts for orthodontically treated
      patients were evaluated before chewing gum; just after chewing gum; and after 45,
      75, 105, and 135 minutes. Saliva samples taken from the patients were inoculated
      onto trypticase-yeast-cystine-bacitracin agar for mutans streptococci and onto
      Rogosa agar for lactobacilli. The agar plates were incubated for 48 hours
      anaerobically at 37 degrees C. The total number of viable bacteria was then
      counted. RESULTS: Just after chewing the mastic gum for 15 minutes, a significant
      decrease of total bacteria and S mutans was observed (P < .001). The reduction in
      lactobacilli was not significant at later first stage (P > .05). However, at the
      end of 135 minutes, there were significantly fewer S mutans (P < .001), total
      viable bacteria (P < .001), and lactobacilli (P < .001) in the oral cavity after
      chewing mastic gum than after chewing paraffin (P < .001). The results show that
      chewing mastic gum decreased the total viable bacteria, S mutans, and
      lactobacilli in saliva in orthodontically treated patients with fixed appliances.
      CONCLUSION: Chewing mastic gum might be useful in preventing caries lesions.

PMID- 17029555
TI  - Mandibular first molar relation to variable lower face skeletal components.
AB  - OBJECTIVE: To evaluate the position of the mandibular first permanent molar in
      the mandible relative to several factors. MATERIALS AND METHODS: A total of 185
      untreated Class I and Class II patients were randomly selected from a sample of
      350 patients from a single office. The palatal and mandibular planes were related
      to Frankfort horizontal to create the interjaw or "B" angle. Age and the mesial
      contact of the mandibular first molars were used. The landmarks were projected at
      right angles to the Frankfort horizontal for effective mandibular dimension
      lengths. Actual-length dimensions were projected at right angles to the
      mandibular plane. Pearson product moment correlation coefficients were computed
      to evaluate the effect of age, cranial length, and mandibular contribution to the
      molar's sagittal position in the mandible. Significance was reported only when P
      < .05 to determine a 95% confidence level. RESULTS: Statistically significant
      positive correlations indicated that the mandibular molar is located more forward
      with increasing age, longer mandibular body length, and increasing posterior
      facial height. In contrast, significant negative correlations to the interjaw,
      mandibular plane, ramal inclination angles, and the linear ramal contribution
      corresponded to a more posterior position of the molar with increasing angles.
      CONCLUSIONS: The mandibular first permanent molar is located more anteriorly with
      an older patient, a longer mandibular body, greater posterior facial height, and
      an acute interjaw angle. In contrast, an increase in the forward tip of the ramus
      places the molar in a more posterior location.

PMID- 17029556
TI  - Simulating properties of in vitro epithelial cell morphogenesis.
AB  - How do individual epithelial cells (ECs) organize into multicellular structures?
      ECs are studied in vitro to help answer that question. Characteristic growth
      features include stable cyst formation in embedded culture, inverted cyst
      formation in suspension culture, and lumen formation in overlay culture.
      Formation of these characteristic structures is believed to be a consequence of
      an intrinsic program of differentiation and de-differentiation. To help discover
      how such a program may function, we developed an in silico analogue in which
      space, events, and time are discretized. Software agents and objects represent
      cells and components of the environment. "Cells" act independently. The "program"
      governing their behavior is embedded within each in the form of axioms and an
      inflexible decisional process. Relationships between the axioms and recognized
      cell functions are specified. Interactions between "cells" and environment
      components during simulation give rise to a complex in silico phenotype
      characterized by context-dependent structures that mimic counterparts observed in
      four different in vitro culture conditions: a targeted set of in vitro phenotypic
      attributes was matched by in silico attributes. However, for a particular growth
      condition, the analogue failed to exhibit behaviors characteristic of
      functionally polarized ECs. We solved this problem by following an iterative
      refinement method that improved the first analogue and led to a second: it
      exhibited characteristic differentiation and growth properties in all simulated
      growth conditions. It is the first model to simultaneously provide a
      representation of nonpolarized and structurally polarized cell types, and a
      mechanism for their interconversion. The second analogue also uses an inflexible
      axiomatic program. When specific axioms are relaxed, growths strikingly
      characteristic of cancerous and precancerous lesions are observed. In one case,
      the simulated cause is aberrant matrix production. Analogue design facilitates
      gaining deeper insight into such phenomena by making it easy to replace low
      resolution components with increasingly detailed and realistic components.

PMID- 17029557
TI  - Natural biocombinatorics in the polyketide synthase genes of the actinobacterium
      Streptomyces avermitilis.
AB  - Modular polyketide synthases (PKSs) of bacteria provide an enormous reservoir of
      natural chemical diversity. Studying natural biocombinatorics may aid in the
      development of concepts for experimental design of genes for the biosynthesis of
      new bioactive compounds. Here we address the question of how the modularity of
      biosynthetic enzymes and the prevalence of multiple gene clusters in Streptomyces
      drive the evolution of metabolic diversity. The phylogeny of ketosynthase (KS)
      domains of Streptomyces PKSs revealed that the majority of modules involved in
      the biosynthesis of a single compound evolved by duplication of a single ancestor
      module. Using Streptomyces avermitilis as a model organism, we have reconstructed
      the evolutionary relationships of different domain types. This analysis suggests
      that 65% of the modules were altered by recombinational replacements that
      occurred within and between biosynthetic gene clusters. The natural reprogramming
      of the biosynthetic pathways was unambiguously confined to domains that account
      for the structural diversity of the polyketide products and never observed for
      the KS domains. We provide examples for natural acyltransferase (AT),
      ketoreductase (KR), and dehydratase (DH)-KR domain replacements. Potential sites
      of homologous recombination could be identified in interdomain regions and within
      domains. Our results indicate that homologous recombination facilitated by the
      modularity of PKS architecture is the most important mechanism underlying
      polyketide diversity in bacteria.

PMID- 17029559
TI  - Application of genome-wide single nucleotide polymorphism typing: simple
      association and beyond.
AB  - The International HapMap Project and the arrival of technologies that type more
      than 100,000 SNPs in a single experiment have made genome-wide single nucleotide
      polymorphism (GW-SNP) assay a realistic endeavor. This has sparked considerable
      debate regarding the promise of GW-SNP typing to identify genetic association in
      disease. As has already been shown, this approach has the potential to localize
      common genetic variation underlying disease risk. The data provided from this
      technology also lends itself to several other lines of investigation;
      autozygosity mapping in consanguineous families and outbred populations, direct
      detection of structural variation, admixture analysis, and other population
      genetic approaches. In this review we will discuss the potential uses and
      practical application of GW-SNP typing including those above and beyond simple
      association testing.

PMID- 17029558
TI  - Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media.
AB  - Otitis media (OM), inflammation of the middle ear, remains the most common cause
      of hearing impairment in children. It is also the most common cause of surgery in
      children in the developed world. There is evidence from studies of the human
      population and mouse models that there is a significant genetic component
      predisposing to OM, yet nothing is known about the underlying genetic pathways
      involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse
      mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This
      develops from acute OM that arises spontaneously in the postnatal period, with
      the age of onset and early severity dependent on the microbiological status of
      the mice and their air quality. We have identified the causal mutation, a
      missense change in the C-terminal zinc finger region of the transcription factor
      Evi1. This protein is expressed in middle ear basal epithelial cells,
      fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when
      inflammatory changes are underway. The identification and characterization of the
      Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates
      a new pathway in genetic predisposition to OM.

PMID- 17029560
TI  - Heterogeneous genomic molecular clocks in primates.
AB  - Using data from primates, we show that molecular clocks in sites that have been
      part of a CpG dinucleotide in recent past (CpG sites) and non-CpG sites are of
      markedly different nature, reflecting differences in their molecular origins.
      Notably, single nucleotide substitutions at non-CpG sites show clear generation
      time dependency, indicating that most of these substitutions occur by errors
      during DNA replication. On the other hand, substitutions at CpG sites occur
      relatively constantly over time, as expected from their primary origin due to
      methylation. Therefore, molecular clocks are heterogeneous even within a genome.
      Furthermore, we propose that varying frequencies of CpG dinucleotides in
      different genomic regions may have contributed significantly to conflicting
      earlier results on rate constancy of mammalian molecular clock. Our conclusion
      that different regions of genomes follow different molecular clocks should be
      considered when inferring divergence times using molecular data and in
      phylogenetic analysis.

PMID- 17029561
TI  - Transposition of reversed Ac element ends generates novel chimeric genes in
      maize.
AB  - The maize Activator/Dissociation (Ac/Ds) elements are members of the hAT (hobo,
      Ac, and Tam3) superfamily of type II (DNA) transposons that transpose through a
      "cut-and-paste" mechanism. Previously, we reported that a pair of Ac ends in
      reversed orientation is capable of undergoing alternative transposition reactions
      that can generate large-scale chromosomal rearrangements, including deletions and
      inversions. We show here that rearrangements induced by reversed Ac ends
      transposition can join the coding and regulatory sequences of two linked
      paralogous genes to generate a series of chimeric genes, some of which are
      functional. To our knowledge, this is the first report demonstrating that
      alternative transposition reactions can recombine gene segments, leading to the
      creation of new genes.

PMID- 17029563
TI  - Tryptophan 171 in Pharaonis phoborhodopsin (sensory rhodopsin II) interacts with
      the chromophore retinal and its substitution with alanine or threonine slowed
      down the decay of M- and O-intermediate.
AB  - Pharaonis phoborhodopsin (ppR), also called pharaonis sensory rhodopsin II,
      NpSRII, is a photoreceptor for the photophobic response of Natronomonas
      pharaonis. Tryptophan 182 (W182) of bacteriorhodopsin (bR) is near the
      chromophore retinal and has been suggested to interact with retinal during the
      photoreaction and also to be involved in the hydrogen-bonding network around the
      retinal. W182 of bR is conserved in ppR as tryptophan 171 (W171). To elucidate
      whether W171 of ppR interacts with retinal during the photoreaction and/or is
      involved in the hydrogen-bonding network as in bR, we formed W171-substituted
      mutants of ppR, W171A and W171T. Our low-temperature spectroscopic study has
      revealed that the substitution of W171 to Ala or Thr resulted in the
      stabilization of M- and O-intermediates. The stability of M and absorption
      spectral changes during the M-decay were different depending on the substituted
      residue. These findings suggest that W171 in ppR interacts with retinal and the
      degree of the interaction depends on the substituted residues, which might be
      rate determining in the M-decay. In addition, the involvement of W171 in the
      hydrogen-bonding network is suggested by the O-decay. We also found that glycerol
      slowed the decay of M and not of O.

PMID- 17029562
TI  - Heat-shock promoters: targets for evolution by P transposable elements in
      Drosophila.
AB  - Transposable elements are potent agents of genomic change during evolution, but
      require access to chromatin for insertion-and not all genes provide equivalent
      access. To test whether the regulatory features of heat-shock genes render their
      proximal promoters especially susceptible to the insertion of transposable
      elements in nature, we conducted an unbiased screen of the proximal promoters of
      18 heat-shock genes in 48 natural populations of Drosophila. More than 200
      distinctive transposable elements had inserted into these promoters; greater than
      96% are P elements. By contrast, few or no P element insertions segregate in
      natural populations in a "negative control" set of proximal promoters lacking the
      distinctive regulatory features of heat-shock genes. P element transpositions
      into these same genes during laboratory mutagenesis recapitulate these findings.
      The natural P element insertions cluster in specific sites in the promoters, with
      up to eight populations exhibiting P element insertions at the same position;
      laboratory insertions are into similar sites. By contrast, a "positive control"
      set of promoters resembling heat-shock promoters in regulatory features harbors
      few P element insertions in nature, but many insertions after experimental
      transposition in the laboratory. We conclude that the distinctive regulatory
      features that typify heat-shock genes (in Drosophila) are especially prone to
      mutagenesis via P elements in nature. Thus in nature, P elements create
      significant and distinctive variation in heat-shock genes, upon which
      evolutionary processes may act.

PMID- 17029564
TI  - Causal cognition in human and nonhuman animals: a comparative, critical review.
AB  - In this article, we review some of the most provocative experimental results to
      have emerged from comparative labs in the past few years, starting with research
      focusing on contingency learning and finishing with experiments exploring
      nonhuman animals' understanding of causal-logical relations. Although the
      theoretical explanation for these results is often inchoate, a clear pattern
      nevertheless emerges. The comparative evidence does not fit comfortably into
      either the traditional associationist or inferential alternatives that have
      dominated comparative debate for many decades now. Indeed, the similarities and
      differences between human and nonhuman causal cognition seem to be much more
      multifarious than these dichotomous alternatives allow.

PMID- 17029566
TI  - Mitochondrial oxidative stress: implications for cell death.
AB  - In addition to the established role of the mitochondria in energy metabolism,
      regulation of cell death has emerged as a second major function of these
      organelles. This seems to be intimately linked to their generation of reactive
      oxygen species (ROS), which have been implicated in mtDNA mutations, aging, and
      cell death. Mitochondrial regulation of apoptosis occurs by mechanisms, which
      have been conserved through evolution. Thus, many lethal agents target the
      mitochondria and cause release of cytochrome c and other pro-apoptotic proteins
      into the cytoplasm. Cytochrome c release is initiated by the dissociation of the
      hemoprotein from its binding to the inner mitochondrial membrane. Oxidation of
      cardiolipin reduces cytochrome c binding and increases the level of soluble
      cytochrome c in the intermembrane space. Subsequent release of the hemoprotein
      occurs by pore formation mediated by pro-apoptotic Bcl-2 family proteins, or by
      Ca(2+) and ROS-triggered mitochondrial permeability transition, although the
      latter pathway might be more closely associated with necrosis. Taken together,
      these findings have placed the mitochondria in the focus of current cell death
      research.

PMID- 17029565
TI  - Research on attention networks as a model for the integration of psychological
      science.
AB  - As Titchener pointed out more than one hundred years ago, attention is at the
      center of the psychological enterprise. Attention research investigates how
      voluntary control and subjective experience arise from and regulate our behavior.
      In recent years, attention has been one of the fastest growing of all fields
      within cognitive psychology and cognitive neuroscience. This review examines
      attention as characterized by linking common neural networks with individual
      differences in their efficient utilization. The development of attentional
      networks is partly specified by genes, but is also open to specific experiences
      through the actions of caregivers and the culture. We believe that the connection
      between neural networks, genes, and socialization provides a common approach to
      all aspects of human cognition and emotion. Pursuit of this approach can provide
      a basis for psychology that unifies social, cultural, differential, experimental,
      and physiological areas, and allows normal development to serve as a baseline for
      understanding various forms of pathology. D.O. Hebb proposed this approach 50
      years ago in his volume Organization of Behavior and continued with introductory
      textbooks that dealt with all of the topics of psychology in a common framework.
      Use of a common network approach to psychological science may allow a foundation
      for predicting and understanding human behavior in its varied forms.

PMID- 17029567
TI  - Pharmacogenomic and structural analysis of constitutive g protein-coupled
      receptor activity.
AB  - G protein-coupled receptors (GPCRs) respond to a chemically diverse plethora of
      signal transduction molecules. The notion that GPCRs also signal without an
      external chemical trigger, i.e., in a constitutive or spontaneous manner,
      resulted in a paradigm shift in the field of GPCR pharmacology. The discovery of
      constitutive GPCR activity and the fact that GPCR binding and signaling can be
      strongly affected by a single point mutation drew attention to the evolving area
      of GPCR pharmacogenomics. For a variety of GPCRs, point mutations have been
      convincingly linked to human disease. Mutations within conserved motifs, known to
      be involved in GPCR activation, might explain the properties of some naturally
      occurring, constitutively active GPCR variants linked to disease. In this review,
      we provide a brief historical introduction to the concept of constitutive
      receptor activity and the pharmacogenomic and structural aspects of constitutive
      receptor activity.

PMID- 17029568
TI  - The impact of glycosylation on the biological function and structure of human
      immunoglobulins.
AB  - Immunoglobulins are the major secretory products of the adaptive immune system.
      Each is characterized by a distinctive set of glycoforms that reflects the wide
      variation in the number, type, and location of their oligosaccharides. In a given
      physiological state, glycoform populations are reproducible; therefore, disease
      associated alterations provide diagnostic biomarkers (e.g., for rheumatoid
      arthritis) and contribute to disease pathogenesis. The oligosaccharides provide
      important recognition epitopes that engage with lectins, endowing the
      immunoglobulins with an expanded functional repertoire. The sugars play specific
      structural roles, maintaining and modulating effector functions that are
      physiologically relevant and can be manipulated to optimize the properties of
      therapeutic antibodies. New molecular models of all the immunoglobulins are
      included to provide a basis for informed and critical discussion. The models were
      constructed by combining glycan sequencing data with oligosaccharide linkage and
      dynamics information from the Glycobiology Institute experimental database and
      protein structural data from "The Protein Data Bank."

PMID- 17029569
TI  - Abstracts of the American Association for Cancer Education 40th Annual Meeting.
      October 12-14, 2006. San Diego, California, USA.

PMID- 17029581
TI  - Regulation of commissural axon pathfinding by slit and its Robo receptors.
AB  - Commissural axons grow along complex pathways toward, across, and beyond the
      midline of the central nervous system. Taking commissural axons in the vertebrate
      spinal cord and the Drosophila ventral nerve cord as examples, we examine how
      commissural axon pathfinding is regulated by the Slit family of guidance cues and
      their Robo family receptors. We extract several principles that seem likely to
      apply to other axons and other contexts, such as the reiterative use of the same
      guidance molecules in distinct pathfinding decisions, the transcriptional
      specification of a pathway, the posttranscriptional regulation of growth along
      the pathway, and the possible role of feedback mechanisms to ensure the fidelity
      of pathfinding choices. Such mechanisms may help explain how a relatively small
      number of guidance molecules can generate complex and stereotyped wiring
      patterns. We also highlight the many gaps in our understanding of commissural
      axon pathfinding and question some widely accepted views. We hope that this
      review encourages further efforts to tackle these questions, in the expectation
      that this system will continue to reveal the general principles of axon
      pathfinding.

PMID- 17029582
TI  - Axonal wiring in the mouse olfactory system.
AB  - The main olfactory epithelium of the mouse is a mosaic of 2000 populations of
      olfactory sensory neurons (OSNs). Each population expresses one allele of one of
      the 1000 intact odorant receptor (OR) genes. An OSN projects a single unbranched
      axon to a single glomerulus, from an array of 1600-1800 glomeruli in the main
      olfactory bulb. Within a glomerulus the OSN axon synapses with the dendrites of
      second-order neurons and interneurons. Axons of OSNs that express the same OR
      project to the same glomeruli-typically one glomerulus per half-bulb and thus
      four glomeruli per mouse. These glomeruli are located at characteristic positions
      within the glomerular layer of the bulb. ORs determine both the odorant response
      profile of the OSN and the projection of its axon to a specific glomerulus. I
      focus on genetic approaches to the axonal wiring problem, particularly on how ORs
      may function in axonal wiring.

PMID- 17029588
TI  - Phagocytosis by Trichomonas vaginalis: new insights.
AB  - BACKGROUND INFORMATION: The parasitic protozoan Trichomonas vaginalis is the
      causative agent of trichomoniasis, a sexually transmitted disease. The phagocytic
      activity of this parasite has not been completely elucidated. In order to better
      understand the mechanisms of trichomonal phagocytosis, we have studied the in
      vitro capacity of T. vaginalis to phagocytose and degrade Saccharomyces
      cerevisiae cells. RESULTS AND CONCLUSIONS: To analyse the phagocytic ability and
      capacity, two isolates of T. vaginalis presenting different virulence grades were
      used. Complementary techniques, such as fluorescence microscopy, computer-based
      fluorescence analysis, scanning and transmission electron microscopy and the use
      of drugs that interfere with the actin microfilaments, were used in order to
      follow the behaviour of the actin cytoskeleton during phagocytosis of yeast cells
      by T. vaginalis. It was concluded that: (1) T. vaginalis changes its shape
      rapidly and engulfs the yeast cells, which are almost as large as the parasite;
      (2) long-term and fresh cultures are able to phagocytose, although the low
      virulence strain JT demonstrated a lower activity when compared with the highly
      virulent T016 isolate; (3) the T016 strain exhibited an amoeboid morphology
      during the internalization of yeast cells in contrast with the JT strain; (4)
      attachment of yeast cells to the parasite occurs via the whole cell surface,
      including both anterior and recurrent flagella; (5) two forms of phagocytosis
      were observed: a 'sinking' process without any apparent participation of plasma
      membrane extensions and the classical phagocytosis where pseudopodia are extended
      toward the target cell; (6) the internalized S. cerevisiae are digested in
      lysosomes; (7) competitor sugars D-mannose or L-fucose inhibit the phagocytosis,
      and inhibition was 1.67 times higher in long-term cultured JT than that of the
      parasites from fresh isolate T016; (8) a thick layer of actin microfilaments was
      present underlying the plasma membrane, and especially in the pseudopodia and
      around the phagocytosed particles; (9) a dramatic change in the distribution
      pattern of fibrillar actin occurred during phagocytosis; (10) cytochalasin D
      depressed the phagocytosis; (11) a non-specific recognition and phagocytosis of
      yeast cells by T. vaginalis is mediated by a mannose receptor present on the
      parasite surface; (12) the phagocytic process may occur simultaneously during
      mitosis of the parasite.

PMID- 17029589
TI  - Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by
      cholesterol.
AB  - MDR1 (multidrug resistance 1)/P-glycoprotein is an ATP-driven transporter which
      excretes a wide variety of structurally unrelated hydrophobic compounds from
      cells. It is suggested that drugs bind to MDR1 directly from the lipid bilayer
      and that cholesterol in the bilayer also interacts with MDR1. However, the
      effects of cholesterol on drug-MDR1 interactions are still unclear. To examine
      these effects, human MDR1 was expressed in insect cells and purified. The
      purified MDR1 protein was reconstituted in proteoliposomes containing various
      concentrations of cholesterol and enzymatic parameters of drug-stimulated ATPase
      were compared. Cholesterol directly binds to purified MDR1 in a detergent soluble
      form and the effects of cholesterol on drug-stimulated ATPase activity differ
      from one drug to another. The effects of cholesterol on K(m) values of drug
      stimulated ATPase activity were strongly correlated with the molecular mass of
      that drug. Cholesterol increases the binding affinity of small drugs (molecular
      mass <500 Da), but does not affect that of drugs with a molecular mass of between
      800 and 900 Da, and suppresses that of valinomycin (molecular mass >1000 Da).
      V(max) values for rhodamine B and paclitaxel are also increased by cholesterol,
      suggesting that cholesterol affects turnover as well as drug binding. Paclitaxel
      stimulated ATPase activity of MDR1 is enhanced in the presence of stigmasterol,
      sitosterol and campesterol, as well as cholesterol, but not ergosterol. These
      results suggest that the drug-binding site of MDR1 may best fit drugs with a
      molecular mass of between 800 and 900 Da, and that cholesterol may support the
      recognition of smaller drugs by adjusting the drug-binding site and play an
      important role in the function of MDR1.

PMID- 17029590
TI  - Polyadenylation proteins CstF-64 and tauCstF-64 exhibit differential binding
      affinities for RNA polymers.
AB  - CstF-64 (cleavage stimulation factor-64), a major regulatory protein of
      polyadenylation, is absent during male meiosis. Therefore a paralogous variant,
      tauCstF-64 is expressed in male germ cells to maintain normal spermatogenesis.
      Based on sequence differences between tauCstF-64 and CstF-64, and on the high
      incidence of alternative polyadenylation in testes, we hypothesized that the RBDs
      (RNA-binding domains) of tauCstF-64 and CstF-64 have different affinities for RNA
      elements. We quantified K(d) values of CstF-64 and tauCstF-64 RBDs for various
      ribopolymers using an RNA cross-linking assay. The two RBDs had similar
      affinities for poly(G)18, poly(A)18 or poly(C)18, with affinity for poly(C)18
      being the lowest. However, CstF-64 had a higher affinity for poly(U)18 than
      tauCstF-64, whereas it had a lower affinity for poly(GU)9. Changing Pro-41 to a
      serine residue in the CstF-64 RBD did not affect its affinity for poly(U)18, but
      changes in amino acids downstream of the C-terminal alpha-helical region
      decreased affinity towards poly(U)18. Thus we show that the two CstF-64
      paralogues differ in their affinities for specific RNA sequences, and that the
      region C-terminal to the RBD is mportant in RNA sequence recognition. This
      supports the hypothesis that tauCstF-64 promotes germ-cell-specific patterns of
      polyadenylation by binding to different downstream sequence elements.

PMID- 17029592
TI  - Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with a multitude of
      functions. Although Cdk5 is widely expressed, it has been studied most
      extensively in neurons. Since its initial characterization, the fundamental
      contribution of Cdk5 to an impressive range of neuronal processes has become
      clear. These phenomena include neural development, dopaminergic function and
      neurodegeneration. Data from different fields have recently converged to provide
      evidence for the participation of Cdk5 in synaptic plasticity, learning and
      memory. In this review, we consider recent data implicating Cdk5 in molecular and
      cellular mechanisms underlying synaptic plasticity. We relate these findings to
      its emerging role in learning and memory. Particular attention is paid to the
      activation of Cdk5 by p25, which enhances hippocampal synaptic plasticity and
      memory, and suggests formation of p25 as a physiological process regulating
      synaptic plasticity and memory.

PMID- 17029591
TI  - Towards abolition of immunogenic structures in insect cells: characterization of
      a honey-bee (Apis mellifera) multi-gene family reveals both an allergy-related
      core alpha1,3-fucosyltransferase and the first insect Lewis-histo-blood-group
      related antigen-synthesizing enzyme.
AB  - Glycoproteins from honey-bee (Apis mellifera), such as phospholipase A2 and
      hyaluronidase, are well-known major bee-venom allergens. They carry N-linked
      oligosaccharide structures with two types of alpha1,3-fucosylation: the
      modification by alpha1,3-fucose of the innermost core GlcNAc, which constitutes
      an epitope recognized by IgE from some bee-venom-allergic patients, and an
      antennal Lewis-like GalNAcbeta1,4(Fucalpha1,3)GlcNAc moiety. We now report the
      cloning and expression of two cDNAs encoding the relevant active alpha1,3-FucTs
      (alpha1,3-fucosyltransferases). The first sequence, closest to that of fruitfly
      (Drosophila melanogaster) FucTA, was found to be a core alpha1,3-FucT (EC
      2.4.1.214), as judged by several enzyme and biochemical assays. The second cDNA
      encoded an enzyme, most related to Drosophila FucTC, that was shown to be capable
      of generating the Le(x) [Galbeta1-4(Fucalpha1-3)GlcNAc] epitope in vitro and is
      the first Lewis-type alpha1,3-FucT (EC 2.4.1.152) to be described in insects. The
      transcription levels of these two genes in various tissues were examined: FucTA
      was found to be predominantly expressed in the brain tissue and venom glands,
      whereas FucTC transcripts were detected at highest levels in venom and
      hypopharyngeal glands. Very low expression of a third homologue of unknown
      function, FucTB, was also observed in various tissues. The characterization of
      these honey-bee gene products not only accounts for the observed alpha1,3
      fucosylation of bee-venom glycoproteins, but is expected to aid the
      identification and subsequent down-regulation of the FucTs in insect cell lines
      of biotechnological importance.

PMID- 17029594
TI  - Neuron-astrocyte interactions in the regulation of brain energy metabolism: a
      focus on NMR spectroscopy.
AB  - An adequate and timely production of ATP by brain cells is of cardinal importance
      to support the major energetic cost of the rapid processing of information via
      synaptic and action potentials. Recently, evidence has been accumulated to
      support the view that the regulation of brain energy metabolism is under the
      control of an intimate dialogue between astrocytes and neurons. In vitro studies
      on cultured astrocytes and in vivo studies on rodents have provided evidence that
      glutamate and Na(+) uptake in astrocytes is a key triggering signal regulating
      glucose use in the brain. With the advent of NMR spectroscopy, it has been
      possible to provide experimental evidence to show that energy consumption is
      mainly devoted to glutamatergic neurotransmission and that glutamate-glutamine
      cycling is coupled in a approximately 1 : 1 molar stoichiometry to glucose
      oxidation, at least in the cerebral cortex. This improved understanding of neuron
      astrocyte metabolic interactions offers the potential for developing novel
      therapeutic strategies for many neurological disorders that include a metabolic
      deficit.

PMID- 17029593
TI  - RNA interference in pain research.
AB  - Within the course of only the last few years, RNA interference (RNAi) has been
      established as a standard technology for investigation of protein function and
      target validation. The present review summarizes recent progress made in the
      application of RNAi in neurosciences with special emphasis on pain research. RNAi
      is a straightforward method to generate loss-of-function phenotypes for any gene
      of interest. In mammals, silencing is induced by small interfering RNAs (siRNAs),
      which have been shown to surpass traditional antisense molecules. Due to its high
      specificity, RNAi has the potential for subtype selective silencing of even
      closely related genes. One of the major challenges for in vivo investigations of
      RNAi remains efficient delivery of siRNA molecules to the relevant tissues and
      cells, particularly to the central nervous system. Various examples will be given
      to demonstrate that intrathecal application of siRNAs is a suitable approach to
      analyse the function of receptors or other proteins that are hypothesized to play
      an important role in pain signalling. Intensive efforts are currently ongoing to
      solve remaining problems such as the risk of off-target effects, the stability of
      siRNA molecules and their efficient delivery to the CNS. RNAi has thus
      demonstrated that it is an extremely valuable tool for the development of new
      analgesic drugs.

PMID- 17029595
TI  - Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma
      IMR-32 cells: modulation by zinc.
AB  - The relevance of a functional cytoskeleton for Nuclear Factor-kappaB (NF-kappaB)
      nuclear translocation was investigated in neuronal cells, using conditions that
      led to a disruption of the cytoskeleton [inhibition of tubulin (vinblastine,
      colchicine), or actin (cytochalasin D) polymerization and zinc deficiency]. We
      present evidence that an impairment in tubulin polymerization can inhibit the
      formation of the complex tubulin-dynein-karyopherin alpha-p50 that is required
      for neuronal retrograde and nuclear NF-kappaB transport. Cells treated with
      vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a
      low nuclear NF-kappaB binding activity, and low nuclear concentrations of RelA
      and p50. The altered nuclear translocation was reflected by a decreased
      transactivation of NF-kappaB-driven genes. The immunocytochemical
      characterization of cellular RelA showed that cytoskeleton disruption can lead to
      an altered distribution of RelA resulting in the formation of peripheral
      accumuli. These results support the concept that cytoskeleton integrity is
      necessary for the transport and translocation of NF-kappaB required for synapse
      to nuclei communication. We suggest that during development, as well as in the
      adult brain, conditions such as zinc deficiency, that affect the normal structure
      and function of the cytoskeleton can affect neuronal proliferation,
      differentiation, and survival by altering NF-kappaB nuclear translocation and
      subsequent impairment of NF-kappaB-dependent gene regulation.

PMID- 17029596
TI  - Differential effect of nerve growth factor on dopaminergic neurotoxin-induced
      apoptosis.
AB  - Both rotenone and manganese are possible neurotoxins for a wide variety of cell
      and neuronal types including dopaminergic neurons and induce apoptosis in various
      cells. Neurotrophic factors have the potential for therapeutic development when
      used to prevent Parkinson's disease. In this paper, we focused on the differences
      between rotenone and manganese as toxins, and characterized the influence of
      neurotrophic factors on toxin-induced apoptosis in PC12 cells. There were
      distinct differences in intracellular mechanisms between rotenone- and manganese
      induced apoptosis such as the production of reactive oxygen species, the response
      to antioxidants, and the activation of the c-Jun N-terminal kinase (JNK) and p38
      mitogen-activated protein kinase (MAPK). Nerve growth factor (NGF) almost
      completely prevented rotenone-induced but not manganese-induced caspase
      activation and DNA fragmentation. The differential effect of NGF was found to be
      mainly due to the down-regulation of the Trk tyrosine kinase receptor by
      manganese but not by rotenone. Prevention of rotenone-induced apoptosis by NGF
      was attenuated by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor,
      LY294002, but not MAPK kinase (MEK) inhibitors, PD98059 or U0126. These results
      demonstrate that the potential neurotoxins for dopaminergic cells exert their
      toxic effect by activation of different signaling pathways of apoptosis and that
      NGF prevents rotenone-induced apoptosis through the activation of the PI 3-kinase
      pathway not MAPK pathway.

PMID- 17029597
TI  - Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell
      proliferation.
AB  - The modulation of cell proliferation in neural progenitor cells (NPCs) is
      believed to play a role in neuronal regeneration. Recent studies showed that K(+)
      channel activity influenced cell proliferation. Therefore, we examined NPCs for
      K(+) channels and tested whether NPC self renewing can be modulated by synthetic
      K(+) channel modulators. The whole-cell K(+) current was partly K(+) dependent
      and showed a cumulative inactivating component. Two tetra-ethyl-ammonium ion
      (TEA)-sensitive K(+) currents with different voltage dependencies ( = 65 microm,
      E(50) = -0.3 +/- 1.3 mV and = 8 mm, E(50) = -15.2 +/- 2.8 mV) and an almost TEA
      insensitive current were identified. Kaliotoxin blocked approximately 50% of the
      entire K(+) currents (IC(50) = 0.25 nm). These properties resembled functional
      characteristics of K(v)1.4, K(v)1.3 and K(v)3.1 channels. Transcripts for these
      channels, as well as proteins for K(v)1.3 and K(v)3.1, were identified.
      Immunocytochemical staining revealed K(v)1.3 and K(v)3.1 K(+) channel expression
      in almost all NPCs. The blockage of K(v)3.1 by low concentrations of TEA, as well
      as the blockage of K(v)1.3 by Psora-4, increased NPC proliferation. These
      findings underline the regulatory role of K(+) channels on the cell cycle and
      imply that K(+) channel modulators might be used therapeutically to activate
      endogenous NPCs.

PMID- 17029598
TI  - Deposition of iron and beta-amyloid plaques is associated with cortical cellular
      damage in rabbits fed with long-term cholesterol-enriched diets.
AB  - Hypercholesterolemia is a potential trigger of Alzheimer's disease, and is
      thought to increase brain levels of beta-amyloid (Abeta) and iron. However,
      animal models to address the mechanisms by which Abeta and iron accumulation may
      cause neuronal damage are poorly defined. To address this question, we fed adult
      rabbits a 1% cholesterol-enriched diet for 7 months. This diet was associated
      with increased regional deposition of both iron and Abeta peptide in the brain.
      Iron preferentially accumulated around Abeta plaques in the adjacent cortex, but
      was not found in the hippocampus. Co-localization of iron and Abeta was
      accompanied by apoptosis, DNA damage, blood-brain barrier (BBB) disruption, as
      well as dysregulation in the level of the iron-regulatory proteins, ferritin and
      heme-oxygenase-1. We further demonstrate that the cholesterol diet-induced
      apoptosis is mediated by the activation of the endoplasmic reticulum stress
      pathway, involving the down-regulation of the endoplasmic reticulum chaperones,
      calreticulin, grp78 and grp94, and the activation of the growth and arrest DNA
      damage protein, gadd153. Our results suggest that BBB damage and disturbances in
      iron metabolism may render the cortex more vulnerable than the hippocampus to the
      cholesterol-induced cellular stress.

PMID- 17029599
TI  - Identification of a new functional target of haloperidol metabolite: implications
      for a receptor-independent role of 3-(4-fluorobenzoyl) propionic acid.
AB  - Haloperidol, a dopamine D2 receptor blocker, is a classical neuroleptic drug that
      elicits extrapyramidal symptoms. Its metabolites include 3-(4-fluorobenzoyl)
      propionic acid (FBPA) and 4-(4-chlorophenyl)-4-piperidinol (CPHP). Until now, the
      biological significance of these metabolites has remained largely unknown. Here,
      we report that the administration of FBPA to mice effected a suppression of
      locomotor activity and induced catalepsy in a manner similar to that observed
      with haloperidol, whereas CPHP had no significant effects. Neither of these two
      metabolites, however, exhibited any ability to bind to the dopamine D2 receptor.
      FBPA blocked dopamine-induced extracellular signal-regulated kinase 1/2
      phosphorylation, and it specifically affected mitogen-activated protein kinase
      kinase (MEK)1/2 activity in hippocampal HN33 cells. Moreover, FBPA was capable of
      direct interaction with MEK1/2, and inhibited its activity in vitro. We
      demonstrated the generation of haloperidol metabolites within haloperidol-treated
      cells by mass spectrometric analyses. Collectively, our results confirm the
      biological activity of FBPA, and provide initial clues as to the receptor
      independent role of haloperidol.

PMID- 17029600
TI  - Regulation of alpha-synuclein expression in alcohol-preferring and -non
      preferring rats.
AB  - The alpha-synuclein (Snca) gene is expressed at higher levels in alcohol-naive,
      inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats.
      Snca modulates dopamine transmission and the dopamineregic system, which play a
      role in mediating the rewarding properties of alcohol consumption. Thus,
      understanding regulation of Snca gene expression could provide insight into the
      relationship of Snca and alcohol consumption. To study regulation of rat Snca
      expression, 1,912 bp of the iP and iNP 5'-regions were cloned and sequenced. 5'
      rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three
      transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that
      the Snca proximal promoter region has a complex architecture. This proximal
      promoter region has three TATA-less core promoters containing SP1 binding sites,
      initiator elements and downstream core promoter elements, which are often located
      in such promoters. Snca-luc constructs transiently transfected into SK-N-SH
      neuroblastoma cells showed that the region from - 1,912 to - 1,746 contained a
      strong core promoter, and that the entire approximately 2 kb region had
      significant promoter activity. Five polymorphisms identified between the iP and
      iNP in the proximal promoter region did not influence differential expression
      between the strains. In contrast, a single nucleotide polymorphism (SNP) at + 679
      in the 3'-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP
      mRNA compared with iNP mRNA, which is consistent with the differential expression
      observed between the iP and iNP strains. These results suggest that regulation of
      rat Snca gene expression is complex and may contribute to alcohol preference in
      the iP rats.

PMID- 17029601
TI  - Nitric oxide production in the basal forebrain is required for recovery sleep.
AB  - Sleep homeostasis is the process by which recovery sleep is generated by
      prolonged wakefulness. The molecular mechanisms underlying this important
      phenomenon are poorly understood. Here, we assessed the role of the intercellular
      gaseous signaling agent NO in sleep homeostasis. We measured the concentration of
      nitrite and nitrate, indicative of NO production, in the basal forebrain (BF) of
      rats during sleep deprivation (SD), and found the level increased by 100 +/- 51%.
      To test whether an increase in NO production might play a causal role in recovery
      sleep, we administered compounds into the BF that increase or decrease
      concentrations of NO. Infusion of either a NO scavenger, 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, or a NO synthase inhibitor,
      N(omega)-nitro-L-arginine methyl ester (L-NAME), completely abolished non-rapid
      eye movement (NREM) recovery sleep. Infusion of a NO donor, (Z)-1-[N-(2
      aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2diolate (DETA/NO), produced
      an increase in NREM that closely resembled NREM recovery after prolonged
      wakefulness. The effects of inhibition of NO synthesis and the pharmacological
      induction of sleep were effective only in the BF area. Indicators of energy
      metabolism, adenosine, lactate and pyruvate increased during prolonged
      wakefulness and DETA/NO infusion, whereas L-NAME infusion during SD prevented the
      increases. We conclude that an increase in NO production in the BF is a causal
      event in the induction of recovery sleep.

PMID- 17029602
TI  - Noncompensation in peptide/receptor gene expression and distinct behavioral
      phenotypes in VIP- and PACAP-deficient mice.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) are closely related neurotrophic peptides of the
      secretin/glucagon family. The two peptides are derived from a common ancestral
      gene and share many functional attributes in neuronal development/regeneration
      which occur not only from overlapping receptor subtype signaling but also through
      common mechanisms regulating their expression. Although PACAP or VIP null mice
      have been generated for study, it is unclear whether the expression of the
      complementary peptide or their receptor systems are altered in a compensatory
      manner during nervous system development. By radioimmunoassay and quantitative
      PCR measurements, we first show that PACAP and VIP have very different temporal
      patterns of expression in developing postnatal mouse brain. In wild-type animals,
      PACAP transcript and peptide levels increased rapidly 2- and 5-fold,
      respectively, within 1 week of age. These levels at 1 week of age were maintained
      through adulthood. VIP transcript and peptide levels, by contrast, increased 25-
      and 50-fold, respectively, over a later time course. In parallel studies of
      development, there were no apparent compensatory increases in brain VIP
      expression in the PACAP knockout animals, PACAP expression in the VIP-deficient
      animals, or receptor mRNA levels in either genotype. To the contrary, there was
      evidence for developmental delays in the expression of peptide and receptor
      transcripts in the knockout animals. A series of behavioral and neurological
      tests demonstrated differences between the knockout genotypes, revealing some
      functional distinctions between the two genes. These results suggest that the
      PACAP and VIP have evolved to possess distinct biological activities and intimate
      that the respective knockout phenotypes represent deficits unmitigated by the
      actions of the complementary related peptide.

PMID- 17029603
TI  - Astrocyte swelling leads to membrane unfolding, not membrane insertion.
AB  - The mechanisms mediating the release of chemical transmitters from astrocytes are
      the subject of intense research. Recent experiments have shown that hypotonic
      conditions stimulate the release of glutamate and ATP from astrocytes, but a
      mechanistic understanding of this process is not available. To determine whether
      hypotonicity activates the process of regulated exocytosis, we monitored membrane
      capacitance by the whole-cell patch-clamp technique whilst a hypotonic medium was
      applied to cultured astrocytes. If exocytosis is triggered under hypotonic
      conditions, as it is following increases in cytosolic calcium, a net increase in
      membrane surface area, monitored by measuring the whole-cell membrane
      capacitance, is expected. Simultaneous measurements of cell size and whole-cell
      membrane conductance and surface area demonstrated that hypotonic medium (210
      mOsm for 200 s) resulted in an increase in membrane conductance and in the
      swelling of cultured astrocytes by an average of 40%, as monitored by cell cross
      sectional area, but without any corresponding change in membrane surface area. As
      we have demonstrated that capacitance measurements have the sensitivity to detect
      increases in cell surface area as small as 0.5%, we conclude that cell swelling
      occurs via an exocytosis-independent mechanism, probably involving the unfolding
      of the plasma membrane.

PMID- 17029604
TI  - Proinsulin/insulin is synthesized locally and prevents caspase- and cathepsin
      mediated cell death in the embryonic mouse retina.
AB  - Programmed cell death is an essential, highly regulated process in neural
      development. Although the role of insulin-like growth factor I in supporting the
      survival of neural cells has been well characterized, studies on
      proinsulin/insulin are scarce. Here, we characterize proinsulin/insulin effects
      on cell death in embryonic day 15.5 mouse retina. Both proinsulin mRNA and
      proinsulin/insulin immunoreactivity were found in the developing retina.
      Organotypic embryonic day 15.5 retinas cultured under growth factor deprivation
      showed an increase in cell death that was reversed by proinsulin, insulin and
      insulin-like growth factor I, with similar median effective concentration values
      via phosphatidylinositol-3-kinase activation. Although insulin and insulin-like
      growth factor I provoked a sustained Akt phosphorylation, proinsulin-induced
      phosphorylation of Akt was not found. Analysis of the growth factor deprivation
      induced cell death mechanisms, using caspase and cathepsin inhibitors,
      demonstrated that both protease families were required for the effective
      execution of cell death. The insulin survival effect, which decreased the extent
      and distribution of cell death to levels similar to those found in vivo, was not
      enhanced by simultaneous treatment with caspase and cathepsin inhibitors,
      suggesting that insulin interferes with these protease pathways in the embryonic
      mouse retina. The mechanisms characterized in this study provide new details on
      early neural cell death and its genuine regulation by insulin/proinsulin.

PMID- 17029605
TI  - Hierarchy and the mechanism of fibril formation in ADan peptides.
AB  - Familial Danish dementia is a neurodegenerative disease which is a consequence of
      alterations in the BRI gene. The pathological signatures of the disease are
      cerebral amyloidolysis, parenchymal protein deposits and neuronal degeneration.
      Synthetic Danish dementia (ADan) peptides are capable of forming fibrillar
      assemblies in vitro at pH 4.8. However, the morphology of the aggregates formed
      depends greatly on the form of the peptides (oxidized or reduced). In addition to
      long slender assemblies (2-5 nm in diameter and several micrometers in length) we
      report ring-like or annular masses (8-9 nm in diameter and 1-2 mm in perimeter)
      in the case of the oxidized form of the peptides. The reduced forms mainly
      aggregate to produce granular heaps. The biophysical and kinetic characterization
      of the process of aggregation was carried out using different spectroscopic and
      imaging techniques. Neurotoxicity assays performed on both the forms reveal that
      the toxicity bears proportionality with the aggregate size.

PMID- 17029606
TI  - Noxp20 and Noxp70, two new markers of early neuronal differentiation, detected in
      teratocarcinoma-derived neuroectodermic precursor cells.
AB  - The murine 1C11 cell line, derived from F9 pluripotent teratocarcinoma cells,
      exhibits features of a bipotential neuronal precursor as it converts into
      serotonergic or catecholaminergic neurons under appropriate induction. In order
      to point out molecular markers expressed in this early neuroectodermic
      commitment, we used a cDNA subtractive hybridization method. The 105 different
      isolated cDNAs represented 75 known genes, expressed sequence tags (EST) or
      genomic fragments. A majority of known proteins encoded by these sequences are
      involved in cellular mobility or migration. We characterized two sequences
      showing identities with ESTs and we called them Noxp20 and Noxp70. The Noxp20
      transcript encodes a putative protein with a predicted caspase recruitment domain
      and the Noxp70 transcript encodes a putative protein displaying a Zn-finger
      domain. Consistent with their roles in neuronal cell development, in situ
      hybridization showed that Noxp20 and Noxp70 are over-expressed in brain. At
      embryonic days 12 and 15, Noxp20 is strongly expressed in the ventricular and
      intermediate zones of the brain and of the spinal cord. At embryonic day 15,
      Noxp70 was found to be strongly expressed in the ventricular zone around the
      telencephalic ventricle, and to a lower extent in the thalamus and hypothalamus.
      At post-natal day 10, Noxp20 mRNA was detected in the dentate gyrus, the
      hippocampus, the cerebellum and the olfactory bulb.

PMID- 17029607
TI  - Platelet count/spleen diameter ratio for the noninvasive diagnosis of esophageal
      varices: results of a multicenter, prospective, validation study.
AB  - BACKGROUND AND AIMS: Noninvasive assessment of esophageal varices (EV) may
      improve the management of patients with cirrhosis and decrease both the medical
      and financial burden related to screening. In this multicenter, international
      study, our aim was to prospectively validate the use of the platelet count/spleen
      diameter ratio for the noninvasive diagnosis of EV. METHODS: A total of 218
      cirrhotic patients underwent screening endoscopy for EV. Platelet count/spleen
      diameter ratio ((N/mm3)/mm) was assessed in all patients and its diagnostic
      accuracy was calculated. On the basis of previous results, a platelet
      count/spleen diameter ratio cutoff of 909 was applied to this population. The
      diagnostic accuracy of the platelet count/spleen diameter ratio was further
      evaluated for both severity and etiology of disease subgroups. RESULTS:
      Prevalence of EV was 54.1%. The platelet count/spleen diameter ratio had 86.0%
      (95% CI, 80.7-90.4%) diagnostic accuracy for EV, which was significantly greater
      as compared with either accuracy of platelet count alone (83.6%, 95% CI 78.0
      88.3%, P= 0.038) or spleen diameter alone (80.2%, 95% CI 74.3-85.3%, P= 0.018).
      The 909 cutoff had 91.5% sensitivity (95% CI 85.0-95.9%), 67.0% specificity (95%
      CI 56.9-76.1%), 76.6% positive predictive value, 87.0% negative predictive value,
      2.77 positive likelihood ratio, and 0.13 negative likelihood ratio for the
      diagnosis of EV. Accuracy of the platelet count/spleen diameter ratio was
      maintained for both severity and etiology of disease subgroups. CONCLUSIONS: The
      platelet count/spleen diameter ratio may be proposed as a safe and reproducible
      means to improve the management of cirrhotic patients who should undergo
      screening endoscopy for EV.

PMID- 17029608
TI  - Physical activity and intestinal gas clearance in patients with bloating.
AB  - BACKGROUND: Patients complaining of abdominal bloating have impaired tolerance
      and clearance of intestinal gas loads. Mild exercise enhances intestinal
      clearance and prevents retention of intestinal gas loads in healthy subjects. Our
      aim was to evaluate the putative beneficial effects of physical activity in
      patients with abdominal bloating. METHODS: In eight patients complaining of
      bloating, seven with irritable bowel syndrome, and one with functional bloating,
      according to Rome II criteria, a gas mixture was continuously infused (12 mL/min)
      into the jejunum for 120 min with simultaneous duodenal lipid perfusion (1
      kcal/min). Gas evacuation, perception (0-6 scale), and abdominal girth were
      measured at 15-min intervals. Paired studies were randomly performed in the
      supine position during intermittent pedaling (5 min with 3-min rest intervals at
      40 rpm and 0.15 kp load) versus rest (as control). RESULTS: During rest, a
      significant proportion of the gas infused was retained in the gut (45 +/- 9%, P <
      0.01 vs basal), but retention was significantly lower during exercise (24 +/- 7%,
      P < 0.05 vs rest). Gas retention during rest was associated with significant
      abdominal symptoms (3.6 score; P < 0.01 vs basal), and symptoms also improved
      during exercise (2.8 score, P < 0.05 vs rest). During the test, patients
      developed abdominal distension, which was related to the volume of gas retained
      (r = 0.68, P < 0.05). CONCLUSION: Mild physical activity enhances intestinal gas
      clearance and reduces symptoms in patients complaining of abdominal bloating.

PMID- 17029609
TI  - Prospective follow-up data from the ProGERD study suggest that GERD is not a
      categorial disease.
AB  - OBJECTIVES: There is a controversy as to whether gastroesophageal reflux disease
      (GERD) exists as a spectrum of disease severity or as a categorial disease in
      three distinct groups: nonerosive (NERD) and erosive reflux disease (ERD) and
      Barrett's esophagus (BE). Aim of the study was to assess progression or
      regression of GERD over 2 yr in a large cohort of patients (N = 3,894) under
      routine clinical care in Germany, Austria, and Switzerland (ProGERD study).
      METHOD: Patients with predominant heartburn, with or without esophagitis, were
      recruited and classified according to endoscopic status at baseline, i.e., NERD,
      erosive reflux disease-Los Angeles (ERD-LA) grade A/B and ERD-LA grade C/D, and
      BE. After an initial treatment with esomeprazole, they were followed, regardless
      of their response. Medical therapy or endoscopy was initiated at the discretion
      of their primary care physician, in line with routine care. At 2 yr, endoscopy
      with biopsy was performed according to the protocol. RESULTS: After 2 yr, 25% of
      patients who had NERD at baseline progressed to LA A/B and 0.6% to LA C/D; 1.6%
      of patients who had LA A/B progressed to LA C/D and 61% regressed to NERD; 42% of
      patients who had LA C/D regressed to LA A/B and 50% regressed to NERD (all
      figures exclude patients with confirmed BE at baseline). At 2 yr, 22% of patients
      had been off medication for at least 3 months. Patients with ERD-LA grade C/D
      were at greatest risk of developing BE: 5.8% compared with 1.4% for ERD-LA grade
      A/B and 0.5% for NERD. CONCLUSION: GERD does not seem to be a categorial disease.
      Progression and regression between grades was observed in this large cohort of
      patients under routine clinical care.

PMID- 17029610
TI  - Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non
      responders to standard interferon or lamivudine.
AB  - OBJECTIVES: Antiviral therapy leads to HBeAg seroconversion in 10-40% of the
      patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in
      progression of liver disease and increased risk of hepatocellular carcinoma. As
      part of a global randomized controlled trial we investigated the efficacy (i.e.,
      loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b)
      in patients who failed to respond to previous courses of standard interferon
      (IFN) or lamivudine. METHODS: We analyzed a total of 76 previous nonresponders:
      37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and
      22 were nonresponders to both therapies. All patients received a 52-wks course of
      100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or
      a placebo. After therapy patients were followed for 26 wks. RESULTS: Thirteen
      (35%) nonresponders to previous IFN, five (29%) nonresponders to previous
      lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to
      treatment with Peg-IFN alpha2b. No difference in response was found for those
      treated with Peg-IFN alpha2b alone or in combination with lamivudine.
      Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) >
      4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those
      with ALT levels <or= 4 x ULN (53%vs 20%, respectively, p= 0.036). CONCLUSIONS:
      Peg-IFN alpha2b is effective in approximately one-third of patients who failed to
      respond to previous treatment with standard IFN or lamivudine. High serum ALT
      level at baseline of Peg-IFN alpha2b therapy was the best predictor for response
      in these patients.

PMID- 17029611
TI  - Acute tryptophan depletion alters gastrointestinal and anxiety symptoms in
      irritable bowel syndrome.
AB  - OBJECTIVES: To assess the effect of acute changes in serotonin (5-HT) synthesis
      using the acute tryptophan depletion (ATD) paradigm on gastrointestinal (GI) and
      mood symptoms in irritable bowel syndrome (IBS). METHODS: In a randomized double
      blind crossover study, 29 subjects (18 patients with ROME II defined IBS and 11
      age-matched controls) were studied under ATD and acute tryptophan increase (ATI)
      conditions. GI symptoms, mood and anxiety ratings, as well as plasma tryptophan
      concentrations were measured. RESULTS: Total (and free) plasma tryptophan
      concentrations decreased on the ATD day in patients (73%[82%]) and controls
      (73%[80%]), and increased on the ATI day in patients (59%[143%]) and controls
      (61%[381%]). Compared with the ATD day, IBS patients reported more GI symptoms on
      the ATI day at +210 (p < 0.001) and at +270 (p < 0.05) min post drink. IBS
      patients also reported less anxiety on the ATI day compared with the ATD day at
      +270 min (p < 0.001). ATD and ATI did not affect these ratings in control
      participants. IBS patients had a lower mood compared with controls (p < 0.05),
      but this did not differ between the ATI and ATD days in either group.
      CONCLUSIONS: IBS patients' GI and anxiety responses to changes in tryptophan load
      differ from controls. This suggests a difference in serotonergic functioning
      between these two groups and provides evidence to support the hypothesis that 5
      HT dysfunction is involved in IBS.

PMID- 17029612
TI  - Psychobiological subtypes of ulcerative colitis: pANCA status moderates the
      relationship between disease activity and psychological distress.
AB  - INTRODUCTION: Studies of psychological factors in ulcerative colitis (UC) have
      produced inconsistent findings. This study sought to determine whether
      perinuclear antineutrophil cytoplasmic antibody (pANCA) demarcates subtypes which
      differ with respect to psychobiological interactions. METHODS: In 148 outpatients
      with UC, the strength of the relationship between current UC disease activity and
      psychological distress was assessed. pANCA was determined by ELISA and
      immunofluorescence, disease activity was determined by symptoms, physical
      examination, and endoscopy using the St. Mark's index, and depressive symptoms
      and health anxiety were measured with self-report scales. Pearson correlations
      between disease activity and depressive symptoms and between disease activity and
      health anxiety were calculated. RESULTS: In 74 pANCA negative subjects, the
      relationship between disease activity and measures of psychological distress was
      significant for disease activity-depression (partial correlation = 0.48, p <
      0.001) and for disease activity-health anxiety (partial correlation = 0.64, p <
      0.001), whereas in 74 pANCA positive subjects, no relationships were found
      (disease activity-depression: partial correlation = 0.18, p= 0.14; disease
      activity-health anxiety: partial correlation = 0.20, p= 0.09). The differences in
      the strength of correlation between pANCA positive and pANCA negative subjects
      were statistically significant for both disease activity-depression (z = 2.0, p=
      0.02) and activity-health anxiety (z = 3.3, p < 0.001). CONCLUSIONS: pANCA status
      demarcates psychobiologically distinct subtypes of UC, such that the absence of
      pANCA is associated with greater psychobiological interaction. These findings
      have implications for clinical care and understanding the pathophysiology of
      intestinal inflammation.

PMID- 17029613
TI  - Relationship between pressure wave amplitude and esophageal bolus clearance
      assessed by combined manometry and multichannel intraluminal impedance
      measurement.
AB  - OBJECTIVES: Esophageal wave amplitude is an important determinant of esophageal
      clearance. A threshold of 30 mmHg is widely accepted as the threshold for
      effective clearance in the distal esophagus. However, the precise relationship
      between wave amplitude and clearance has received relatively little attention.
      The aim of this study was to assess the impact of peristaltic wave amplitude on
      esophageal volume clearance using multiple intraluminal impedance (MII)
      measurement. METHODS: Concurrent manometry and MII were performed on 42 healthy
      asymptomatic volunteers and 13 patients with ineffective esophageal motility.
      Esophageal motility was measured at four sites 5-cm apart, starting 2 cm above
      the lower esophageal sphincter. MII was measured at corresponding sites with
      electrodes incorporated into the manometric assembly. Ten 5-mL liquid (saline)
      boluses and ten 5-mL low impedance viscous boluses were tested in each subject.
      Pressure wave amplitude was determined at each site as well as peristaltic
      success of the responses. Bolus clearance was measured from individual recording
      segment and from the esophagus as a whole. RESULTS: The proportion of liquid
      boluses cleared at each site was directly related to wave amplitude and did not
      increase significantly above a threshold of 25 mmHg in the proximal esophagus, 22
      mmHg in the mid-esophagus, and 30 mmHg in the distal esophagus. Corresponding
      wave amplitudes for total esophageal clearance were 35-40 mmHg. There was a good
      correlation between the wave amplitude at one site of the esophagus and those of
      the rest of the esophagus. For both liquid and viscous boluses, the likelihood of
      impaired clearance was directly related to the number of segments with
      hypotensive pressure waves. CONCLUSION: The findings confirm the validity of the
      wave amplitude threshold required for effective liquid bolus clearance and have
      established the amplitude threshold for clearance of viscous boluses. However,
      the number of hypotensive pressure waves required for the definition of
      ineffective motility may be too low.

PMID- 17029614
TI  - Chronic alcohol consumption is a major risk factor for pancreatic necrosis in
      acute pancreatitis.
AB  - BACKGROUND: Much of the late morbidity and mortality of acute pancreatitis (AP)
      is attributed to complications of pancreatic necrosis (PNEC). Early diagnosis of
      PNEC in high-risk patients is critical to management. Hemoconcentration is one
      risk factor for PNEC, but additional risk factors are likely implicated. AIMS:
      (1) To evaluate a series of preselected clinical factors in a prospectively
      collected cohort with AP to identify risk factors for PNEC and (2) to verify the
      relative risk of any newly identified factor(s) by retrospective analysis of a
      large patient cohort. METHODS: Phase I: 102 AP patients were prospectively
      ascertained, of which 77 (mean age 49 yr; 35 women, 42 men) underwent contrast
      enhanced computerized tomography (CECT) and were studied. Eleven subjects
      developed PNEC (14%). Binary logistic regression was performed to identify any
      clinical factors associated with PNEC. Phase II: 1,474 anonymized patients
      admitted to the hospital with a diagnosis of AP were electronically reviewed to
      identify 359 subjects (mean age 54 yr; 157 women, 202 men) with AP and CECT.
      Seventy-six of these patients (21%) exhibited CECT evidence of PNEC. The
      associations found in the Phase I group were compared with Phase II by logistic
      regression analysis. RESULTS: In Phase I, only chronic alcohol consumption was
      identified as a significant new risk factor for the development of PNEC (6/19 vs
      5/58, p= 0.02, OR 4.8, CI 1.27-18.2). In Phase II, it was verified that excessive
      alcohol consumption was a significant risk factor for PNEC (18/52 vs 58/307, p=
      0.012, OR 2.27, CI 1.19-4.30). CONCLUSION: Chronic alcohol consumption seems to
      constitute a strong risk factor for PNEC.

PMID- 17029615
TI  - Experience with type A botulinum toxin for treatment of outlet-type constipation.
AB  - BACKGROUND: Puborectalis syndrome remains a therapeutic challenge for today's
      physicians. Traditional approaches include use of fiber, laxatives, enemas,
      biofeedback training, and surgery. These often were tried sequentially and had
      conflicting or even disappointing results. We investigated the efficacy of
      injections of botulinum toxin in improving rectal emptying in patients with
      defecatory disorders involving spastic pelvic-floor muscles. METHODS: Twenty-four
      consecutive patients with chronic outlet obstruction constipation resulting from
      puborectalis syndrome were included in the study. The patients were treated with
      60 units of type A botulinum toxin, injected into two sites on either side of the
      puborectalis muscle under ultrasonographic guidance. RESULTS: At 2 months,
      evaluation inspection revealed a symptomatic improvement in 19 patients.
      Anorectal manometry demonstrated decreased tone during straining from 98 +/- 24
      to 56 +/- 20 mmHg at a 1-month evaluation (p < 0.01) and 56 +/- 29 mmHg at a 2
      month follow-up (p < 0.01). Pressure during straining was lower than resting anal
      pressure at the same time in all patients. Defecography after the treatment
      showed improvement in anorectal angle during straining, which increased from 98
      +/- 9 degrees to 121 +/- 15 degrees (p < 0.01). CONCLUSIONS: Botulinum toxin
      injections should be considered as a simple therapeutic approach in patients with
      obstructed defecation. The treatment is safe and effective, especially with the
      use of the ultrasonographic guidance that accounts for a more precise injection
      and consequently better long-term results. Otherwise, given the limited effect of
      the toxin, repeated injections may be necessary to maintain the clinical
      improvement.

PMID- 17029616
TI  - Noninvasive markers of liver fibrosis and inflammation in chronic hepatitis B
      virus related liver disease.
AB  - BACKGROUND/AIMS: Noninvasive markers for predicting significant fibrosis and
      inflammation have not yet been validated in an unselected group of chronic
      hepatitis B virus (HBV) carriers. The aim of this study was to create noninvasive
      models to predict significant fibrosis and inflammation in chronic HBV carriers.
      METHODS: A total of 276 (229 HBeAg negative, 47 HBeAg positive) unselected
      consecutive treatment naive patients chronically infected with HBV who attended
      our center over a 36-month period underwent liver biopsy. HBeAg negative patients
      were randomly divided into two cohorts: training group (N = 130) and validation
      group (N = 99). HBeAg positive patients were analyzed as a whole without
      separation. Thirteen parameters were analyzed separately in HBeAg negative and
      HBeAg positive patients to predict significant fibrosis (Ishak stage >or=3) and
      inflammation (Ishak grade >or=7). RESULTS: In HBeAg negative patients significant
      liver fibrosis was best predicted using the variables HBV DNA levels, alkaline
      phosphatase, albumin, and platelet counts with an area under ROC curve (AUC) of
      0.91 for the training group and 0.85 for the validation group. Using the low
      cutoff probability of 4.72, significant fibrosis could be excluded with negative
      predictive value of 99% in the entire cohort, and liver biopsy would have been
      avoided in 52% of patients. The best model for predicting significant
      inflammation included the variables age, HBV DNA levels, AST, and albumin with an
      AUC of 0.93 in the training and 0.82 in the validation group. In HBeAg positive
      patients no factor could predict accurately stages of liver fibrosis, but the
      best factor for predicting significant inflammation was AST with an AUC of 0.87.
      CONCLUSIONS: Significant hepatic fibrosis and necroinflammation can reliably be
      predicted using routinely checked tests and HBV DNA levels.

PMID- 17029617
TI  - Noncardia gastric adenocarcinoma remains an important and deadly cancer in the
      United States: secular trends in incidence and survival.
AB  - BACKGROUND: Noncardia gastric adenocarcinoma is not frequently mentioned in the
      United States. However, it is unclear if the previously reported decline in
      noncardia gastric adenocarcinoma has continued, and if detection and management
      has affected overall survival outside the setting of clinical trials. METHODS: We
      used the Surveillance, Epidemiology, and End Results registry (SEER) to identify
      all cases of noncardia gastric adenocarcinoma diagnosed between 1973 and 2002.
      The yearly age-adjusted incidence rates and the relative survival rates were
      calculated. Cox proportional hazards (PH) models were used to examine temporal
      trends from 1983 to 2003. RESULTS: Between 1973 and 2002, there were 24,103 cases
      of noncardia gastric adenocarcinoma. The age-adjusted yearly incidence rate
      declined by 23% between 1973 and 2002 from 4.3 to 3.3 per 100,000 person-years.
      However, the incidence of localized noncardia gastric adenocarcinoma (invasive
      neoplasm confined to the organ of origin) remained without change between 0.9 and
      1.0 per 100,000 person-years, and increased with age, especially in the 85+ yr
      age group (a 47% increase between 1973 and 2002). The incidence rates in men were
      double those in women, and 1.6-fold and 2.6-fold higher in blacks and other races
      (mostly Asians), respectively, compared with whites. Patients with radiation and
      chemotherapy after gastrectomy had a 22% better mortality risk compared with
      those treated with gastrectomy alone. The Cox PH analysis shows no significant
      change in mortality risk related to year of diagnosis between 1983 and 2002, both
      in unadjusted as well as adjusted analyses. However, there were significant
      independent regional and racial variations in survival. Asians had a 17% lower
      mortality risk compared with whites. CONCLUSIONS: Despite the overall decline in
      noncardia gastric adenocarcinoma, the incidence of local stage disease has
      remained stable in most ages and even increased in old ages. Unfortunately, there
      has been no significant improvement in survival during the past 20 yr. Moreover,
      there remain considerable regional as well as racial variations in mortality.

PMID- 17029619
TI  - Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate
      malignant and benign pancreatic masses.
AB  - OBJECTIVES: Accurate diagnosis of malignant and benign pancreatic masses can be
      challenging, potentially delaying treatment for cancer and subjecting patients
      with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle
      aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of
      patients. The role of EUS-FNA molecular analysis in this context is studied.
      METHODS: Patients with benign pancreatic masses (6 cases, 4 autoimmune
      pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15)
      with inconclusive cytology (5 cases) and positive cytology (10 controls) were
      selected. All cases had definitive pathology. Representative cells were
      microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16
      microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q,
      21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary
      electrophoresis for quantitative determination of allelic imbalance. k-ras-2
      point mutation analysis was also performed. Mean fractional mutation rate (FMR)
      was calculated and compared for each group. RESULTS: All malignant cases carried
      multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or
      suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no
      mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions
      exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign
      samples was significantly different (p < 0.0001). CONCLUSIONS: Broad panel
      microsatellite loss and k-ras point mutation analysis can be reliably performed
      on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy.
      Furthermore, it accurately differentiates between malignant and benign pancreatic
      masses.

PMID- 17029618
TI  - Safety and colon-cleansing efficacy of a new residue-free formulation of sodium
      phosphate tablets.
AB  - OBJECTIVE: A residue-free sodium phosphate tablet (RF-NaP) was formulated that
      lacks microcrystalline cellulose, which can appear as a whitish residue in the
      colon. A multicenter, randomized, investigator-blinded study was conducted to
      compare the colon-cleansing efficacy of 40 or 32 tablets of RF-NaP with the
      marketed 40-tablet NaP treatment regimen. METHODS: Eight hundred sixteen patients
      were randomized prior to colonoscopy to receive either 40 tablets (60 g) of NaP
      or RF-NaP or 32 tablets (48 g) of RF-NaP. Colon cleansing was assessed using a 4
      point scale based on retained "colonic contents." The primary end point was
      overall colon-cleansing response rate to treatment (score of excellent/good)
      versus nonresponse (fair/inadequate). RESULTS: Seven hundred four patients were
      included in the efficacy analysis. The overall colon-cleansing response rates
      were comparable among treatment arms (94.5%, 97.0%, and 95.3% for NaP, RF-NaP 40,
      and RF-NaP 32 tablets, respectively). Ascending colon-cleansing response rates
      for RF-NaP 40 (95.7%) and 32 tablets (93.6%) were significantly better than for
      NaP tablets (88.5%, p < 0.03 for both). Patients treated with RF-NaP 32 tablets
      experienced less pronounced changes in electrolyte levels and fewer adverse
      events (138/239, 58%) compared with patients receiving NaP (161/238, 68%, p=
      0.07) and RF-NaP 40 tablets (156/236, 66%, p= 0.03). The most common adverse
      events reported were abdominal distention, nausea, abdominal pain, and vomiting.
      CONCLUSIONS: Based on the safety, efficacy, and patient preferences, the 32
      tablet RF-NaP regimen was superior to the 40-tablet RF-NaP and NaP regimen for
      colon cleansing prior to colonoscopy.

PMID- 17029620
TI  - Biliary tract candidiasis: diagnostic and therapeutic approaches in a case
      series.
AB  - BACKGROUND: Biliary obstruction with its wide range of potential causes is a
      common disorder in gastroenterology. Infections of the biliary tract with Candida
      and other fungal species leading to obstructive jaundice have increasingly been
      recognized in the last few years. Besides a few case reports, there are few data
      in the literature giving us an idea how to diagnose and treat these patients.
      METHODS: We report on a series of seven patients suffering from biliary tract
      candidiasis who were diagnosed and treated at our institution. Predisposition
      factors, reliability of various diagnostic modalities, and treatment options
      based on our own experience are presented and discussed. RESULTS: Besides the
      general diagnostic modalities such as laboratory findings or ultrasonography, we
      often observed mycelia in the bile duct system endoscopically. Typical
      morphological changes in peripheral bile ducts could be detected during
      endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and
      subsequent microbiological analysis in combination with ERCP findings revealed
      diagnosis of bile duct candidiasis in all cases. Treatment included both
      antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage,
      or debridement. With respect to fungal eradication, therapy was successful in 71%
      of cases as proven by microbiological analysis of bile aspirates. Since many of
      these patients suffer not only from biliary mycosis but also from disease
      necessitating immunosuppression, the prognosis was poor in some cases.
      CONCLUSION: Biliary tract candidiasis because of immunosuppression is an
      increasingly recognized disease and remains a major clinical challenge. Besides
      laboratory analysis and ultrasonography, diagnostic modalities should include
      aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug
      treatment as the main therapeutic column for biliary candidiasis should be
      complemented by endoscopic intervention.

PMID- 17029621
TI  - Predicting iron and folate deficiency anaemias from standard blood testing: the
      mechanism and implications for clinical medicine and public health in developing
      countries.
AB  - BACKGROUND: Developing countries have high prevalence of diseases, but facilities
      to diagnose and treat them are limited. We must use available resources in ways
      not needed where there are sophisticated equipment and trained staff. Anaemia is
      common; iron deficiency affects health and productivity; folate deficiency in
      pregnant women causes foetal abnormalities. Few developing countries can measure
      serum folate or ferritin, but standard automated blood analyses are widely
      available and can help predict folate and iron deficiency. The RDW-CV%
      (coefficient of variation of the red cell width) measures the variability in the
      size of red blood cells (RBC) in routine automated analysis of blood cells, but
      is seldom reported. Levels of RDW-CV% and haemoglobin (Hb) can predict iron
      deficiency anaemia. METHOD AND RESULTS: I have written a computer model based on
      the standard mechanism for blood formation and destruction. This shows that
      before anaemia develops and during recovery, there are both normal and abnormal
      RBC (small in iron deficiency and large in folate deficiency) in the circulation.
      The model calculates the abnormality in the RDW-CV% in standard automated blood
      analyses. In early iron deficiency and during recovery the full blood count shows
      the Hb near the lower limit of normal, a low MCV and a high RDW-CV%. A similar
      pattern, but with a higher MCV, develops in folate deficiency. Folate deficiency
      is often brief and may not cause anaemia. The high RDW-CV% may persist for three
      months. CONCLUSION: This long footprint could be medically useful for detecting
      folate deficiency and so limiting foetal damage in individuals and communities.
      Few clinicians or public health workers know about RDW-CV%. Standard blood
      reports for clinical use should include the RDW-CV% and note the possible
      significance of abnormal values.

PMID- 17029622
TI  - Timing and risk factors for clinical fractures among postmenopausal women: a 5
      year prospective study.
AB  - BACKGROUND: Many risk factors for fractures have been documented, including low
      bone-mineral density (BMD) and a history of fractures. However, little is known
      about the short-term absolute risk (AR) of fractures and the timing of clinical
      fractures. Therefore, we assessed the risk and timing of incident clinical
      fractures, expressed as 5-year AR, in postmenopausal women. METHODS: In total, 10
      general practice centres participated in this population-based prospective study.
      Five years after a baseline assessment, which included clinical risk factor
      evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80
      years, were re-examined, including undergoing an evaluation of clinical fractures
      after menopause. Risk factors for incident fractures at baseline that were
      significant in univariate analyses were included in a multivariate Cox survival
      regression analysis. The significant determinants were used to construct
      algorithms. RESULTS: In the total group, 12.5% (95% confidence interval (CI) 10.1
      14.9) of the women experienced a new clinical fracture. A previous clinical
      fracture after menopause and a low BMD (T-score <-1.0) were retained as
      significant predictors with significant interaction. Women with a recent previous
      fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0-58.1) versus
      21.2% (95% CI 20.7-21.6) if the previous fracture had occurred earlier. In women
      without a fracture history, the AR was 13.8% (95% CI 10.9-16.6) if BMD was low
      and 7.0% (95% CI 5.5-8.5) if BMD was normal. CONCLUSION: In postmenopausal women,
      clinical fractures cluster in time. One in two women with a recent clinical
      fracture had a new clinical fracture within 5 years, regardless of BMD. The 5
      year AR for a first clinical fracture was much lower and depended on BMD.

PMID- 17029623
TI  - A model of gene-gene and gene-environment interactions and its implications for
      targeting environmental interventions by genotype.
AB  - BACKGROUND: The potential public health benefits of targeting environmental
      interventions by genotype depend on the environmental and genetic contributions
      to the variance of common diseases, and the magnitude of any gene-environment
      interaction. In the absence of prior knowledge of all risk factors, twin, family
      and environmental data may help to define the potential limits of these benefits
      in a given population. However, a general methodology to analyze twin data is
      required because of the potential importance of gene-gene interactions
      (epistasis), gene-environment interactions, and conditions that break the 'equal
      environments' assumption for monozygotic and dizygotic twins. METHOD: A new model
      for gene-gene and gene-environment interactions is developed that abandons the
      assumptions of the classical twin study, including Fisher's (1918) assumption
      that genes act as risk factors for common traits in a manner necessarily
      dominated by an additive polygenic term. Provided there are no confounders, the
      model can be used to implement a top-down approach to quantifying the potential
      utility of genetic prediction and prevention, using twin, family and
      environmental data. The results describe a solution space for each disease or
      trait, which may or may not include the classical twin study result. Each point
      in the solution space corresponds to a different model of genotypic risk and gene
      environment interaction. CONCLUSION: The results show that the potential for
      reducing the incidence of common diseases using environmental interventions
      targeted by genotype may be limited, except in special cases. The model also
      confirms that the importance of an individual's genotype in determining their
      risk of complex diseases tends to be exaggerated by the classical twin studies
      method, owing to the 'equal environments' assumption and the assumption of no
      gene-environment interaction. In addition, if phenotypes are genetically robust,
      because of epistasis, a largely environmental explanation for shared sibling risk
      is plausible, even if the classical heritability is high. The results therefore
      highlight the possibility--previously rejected on the basis of twin study results
      -that inherited genetic variants are important in determining risk only for the
      relatively rare familial forms of diseases such as breast cancer. If so, genetic
      models of familial aggregation may be incorrect and the hunt for additional
      susceptibility genes could be largely fruitless.

PMID- 17029624
TI  - Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced
      by heterozygous mutation of Pax6.
AB  - BACKGROUND: Knowledge of the consequences of heterozygous mutations of
      developmentally important genes is important for understanding human genetic
      disorders. The Gli3 gene encodes a zinc finger transcription factor and
      homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for
      mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall
      syndromes, in which limb defects are prominent, and mice heterozygous for similar
      mutations have extra digits. Here we examined whether eye development, which is
      abnormal in mice lacking functional Gli3, is defective in Gli3+/- mice. RESULTS:
      We showed that Gli3 is expressed in the developing eye but that Gli3+/- mice have
      only very subtle eye defects. We then generated mice compound heterozygous for
      mutations in both Gli3 and Pax6, which encodes another developmentally important
      transcription factor known to be crucial for eye development. Pax6+/-; Gli3+/-
      eyes were compared to the eyes of wild-type, Pax6+/- or Gli3+/- siblings. They
      exhibited a range of abnormalities of the retina, iris, lens and cornea that was
      more extensive than in single Gli3+/- or Pax6+/- mutants or than would be
      predicted by addition of their phenotypes. CONCLUSION: These findings indicate
      that heterozygous mutations of Gli3 can impact on eye development. The importance
      of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene
      dosage, suggesting that the two genes co-operate during eye morphogenesis.

PMID- 17029625
TI  - Comparative genomics of fungal allergens and epitopes shows widespread
      distribution of closely related allergen and epitope orthologues.
AB  - BACKGROUND: Allergy is a common debilitating and occasionally life threatening
      condition. The fungal kingdom contains a number of species that produce a wide
      range of well defined protein allergens although the vast majority of fungal
      species have unknown allergenic potential. The recent genome sequencing of a
      variety of fungi provides the opportunity to assess the occurrence of allergen
      orthologues across the fungal kingdom. Here we use comparative genomics to survey
      the occurrence of allergen orthologues in fungi. RESULTS: A database of 82
      allergen sequences was compiled and used to search 22 fungal genomes.
      Additionally we were able to model allergen structure for representative members
      of several highly homologous allergen orthologue classes. We found that some
      allergen orthologue classes that had predicted structural congruence to allergens
      and allergen epitopes were ubiquitous in all fungi. Other allergen orthologues
      classes were less well conserved and may not possess conserved allergen epitope
      orthologues in all fungi. A final group of allergen orthologues, including the
      major allergens Asp f 1 and Alt a 1, appear to be present in only a limited
      number of species. CONCLUSION: These results imply that most fungi may possess
      proteins that have potential to be allergens or to cross react with allergens.
      This, together with the observation that important allergens such as Asp f 1 are
      limited to genera or species, has significant implications for understating
      fungal sensitization, and interpreting diagnosis and management of fungal
      allergy.

PMID- 17029626
TI  - Relating tissue specialization to the differentiation of expression of singleton
      and duplicate mouse proteins.
AB  - BACKGROUND: Gene duplications have been hypothesized to be a major factor in
      enabling the evolution of tissue differentiation. Analyses of the expression
      profiles of duplicate genes in mammalian tissues have indicated that, with time,
      the expression patterns of duplicate genes diverge and become more tissue
      specific. We explored the relationship between duplication events, the time at
      which they took place, and both the expression breadth of the duplicated genes
      and the cumulative expression breadth of the gene family to which they belong.
      RESULTS: We show that only duplicates that arose through post-multicellularity
      duplication events show a tendency to become more specifically expressed, whereas
      such a tendency is not observed for duplicates that arose in a unicellular
      ancestor. Unlike the narrow expression profile of the duplicated genes, the
      overall expression of gene families tends to maintain a global expression
      pattern. CONCLUSION: The work presented here supports the view suggested by the
      subfunctionalization model, namely that expression divergence in different
      tissues, following gene duplication, promotes the retention of a gene in the
      genome of multicellular species. The global expression profile of the gene
      families suggests division of expression between family members, whose expression
      becomes specialized. Because specialization of expression is coupled with an
      increased rate of sequence divergence, it can facilitate the evolution of new,
      tissue-specific functions.

PMID- 17029627
TI  - Prognostic factors affecting survival after surgical resection of
      gastrointestinal stromal tumours: a two-unit experience over 10 years.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common
      mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been
      recently described based on their specific immunohistochemistry and the presence
      of particular KIT-related mutations which potentially make them targets for
      tyrosine kinase inhibition. METHODS: Sixty-one patients (29 M; 32 F, median age
      60 years; range: 23-86 years) between June 1994 and March 2005, were analyzed
      from two allied institutions. Patient, tumour, and treatment variables were
      analyzed to identify factors affecting survival. RESULTS: Of the 61 patients, 55
      (90%) underwent complete surgical resection of macroscopic disease. The 5-year
      overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free
      survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis
      revealed that R0 resection was strongly associated with a better OSrate (p <
      0.0001). Likewise, univariate analysis also showed high mitotic count of > 10
      mitoses/per 50 HPF was a significant variable in worse prognosis for OS (<or= 10
      mitoses/per 50 HPF 95% 5-year OS vs. > 10 mitoses/per 50 HPF 74% 5-year OS,
      respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic
      count remained as a significant negative prognostic variable for OS (p = 0.029).
      Among patients resected for cure, there were 8 recurrences during follow-up. The
      mean time to recurrence was 21 +/- 10 months (range: 4-36 months). Univariate
      analysis revealed that mitotic count of > 10 mitoses per 50 high power fields,
      intratumoural necrosis, and pathological tumour size (> 10 cm in maximal
      diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02,
      respectively), with tumour necrosis and high mitotic count remaining as
      independent predictive variables affecting prognosis on subsequent multivariate
      analysis. CONCLUSION: Most GISTs are resectable with survival principally
      dependent upon mitotic count and completeness of resection. Future metabolic and
      genetic analyses will define the role of and resistance to induction or
      postoperative adjuvant targeted kinase inhibition therapy.

PMID- 17029628
TI  - Feedback on the FDA's February 2006 draft guidance on Patient Reported Outcome
      (PRO) measures from a developer of PRO measures.
AB  - I believe that the FDA guidelines have already had an impact in encouraging good
      practice in the use of PROs. There are, however, important improvements that need
      to be made to the guidelines, particularly in the use of health status and
      quality of life terminology. It is essential to distinguish between health status
      and quality of life and to use both terms. Nothing is to be gained and a great
      deal will be lost if the term quality of life (which has been misused as an
      umbrella term in the past) is abandoned and replaced with the term health status.
      Patients want us to consider their quality of life as well as their health. To
      abandon the term would be to forget about their quality of life and focus only on
      their health. Patients are well able to tell us what quality of life means to
      them and to rate the impact of a condition on their quality of life if we use
      individualised quality of life measures and individualised condition-specific
      quality of life measures to allow them to do so. Although my experience with PRO
      measures would support many of the recommendations in the guidelines there are
      others that I would not fully agree with or would contradict on the basis of my
      own research evidence. I have provided references to that research and hope that
      the FDA will feel able to do the same when they finalize their guidelines.

PMID- 17029629
TI  - Prognostic significance of fascin expression in advanced colorectal cancer: an
      immunohistochemical study of colorectal adenomas and adenocarcinomas.
AB  - BACKGROUND: Fascin is an actin bundling protein with roles in the formation of
      cell protrusions and motility of mesenchymal and neuronal cells. Fascin is
      normally low or absent from epithelia, but is upregulated in several epithelial
      neoplasms where it may contribute to an invasive phenotype. Here, we report on
      the prevalence and potential clinical significance of fascin expression in
      relation to the progression of colorectal adenocarcinoma and to tumor cell
      proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of
      107 colorectal adenomas and 35 adenocarcinomas were analyzed by
      immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67
      proliferation index were also investigated by use of a tissue microarray
      containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas
      linked to a CCF, IRB-approved database with a mean of 38 months of clinical
      follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox
      regression methods. RESULTS: Fascin was not expressed by the normal colonic
      epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas
      showed fascin expression in greater than 10% of the tumor cells. In the
      clinically-annotated tumors, fascin immunoreactivity was more common in tumors
      located in the proximal colon (p = 0.009), but was not associated with age,
      gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with
      strong fascin immunoreactivity had a worse prognosis than patients with low or
      absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative
      patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely
      correlated at the cellular level; this trend was less apparent in
      adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas,
      where its expression is often focal. Strong and diffuse expression was seen in a
      subset of advanced colorectal adenocarcinomas that correlated with shorter
      survival in stage III and IV patients. Fascin may have prognostic value as an
      early biomarker for more aggressive colorectal adenocarcinomas.

PMID- 17029630
TI  - Microarray analysis after RNA amplification can detect pronounced differences in
      gene expression using limma.
AB  - BACKGROUND: RNA amplification is necessary for profiling gene expression from
      small tissue samples. Previous studies have shown that the T7 based amplification
      techniques are reproducible but may distort the true abundance of targets.
      However, the consequences of such distortions on the ability to detect biological
      variation in expression have not been explored sufficiently to define the true
      extent of usability and limitations of such amplification techniques. RESULTS: We
      show that expression ratios are occasionally distorted by amplification using the
      Affymetrix small sample protocol version 2 due to a disproportional shift in
      intensity across biological samples. This occurs when a shift in one sample
      cannot be reflected in the other sample because the intensity would lie outside
      the dynamic range of the scanner. Interestingly, such distortions most commonly
      result in smaller ratios with the consequence of reducing the statistical
      significance of the ratios. This becomes more critical for less pronounced ratios
      where the evidence for differential expression is not strong. Indeed, statistical
      analysis by limma suggests that up to 87% of the genes with the largest and
      therefore most significant ratios (p < 10e(-20)) in the unamplified group have a
      p-value below 10e(-20) in the amplified group. On the other hand, only 69% of the
      more moderate ratios (10e(-20) < p < 10e(-10)) in the unamplified group have a p
      value below 10e(-10) in the amplified group. Our analysis also suggests that,
      overall, limma shows better overlap of genes found to be significant in the
      amplified and unamplified groups than the Z-scores statistics. CONCLUSION: We
      conclude that microarray analysis of amplified samples performs best at detecting
      differences in gene expression, when these are large and when limma statistics
      are used.

PMID- 17029631
TI  - Amlodipine versus angiotensin II receptor blocker; control of blood pressure
      evaluation trial in diabetics (ADVANCED-J).
AB  - BACKGROUND: The coexistence of type 2 diabetes mellitus and hypertension
      increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes
      Study has shown that blood pressure control as well as blood glucose control is
      efficient for prevention of complications in hypertensive patients with diabetes
      mellitus. However, some reports have shown that it is difficult to control the
      blood pressure and the concomitant use of a plurality of drugs is needed in
      hypertensive patients with diabetes mellitus. In recent years renin-angiotensin
      system depressants are increasingly used for the blood pressure control in
      diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are
      increasingly used. However, there is no definite evidence of the point of which
      is efficient for the control, the increase in dose of A II antagonist or the
      concomitant use of another drug, in hypertensive patients whose blood pressure
      levels are inadequately controlled with A II antagonist. METHODS/DESIGN:
      Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who
      have been treated by the single use of AII antagonist at usual doses for at least
      8 weeks or patients who have been treated by the concomitant use of AII
      antagonist and an antihypertensive drug other than calcium channel blockers and
      ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION: We
      designed a multi-center, prospective, randomized, open label, blinded-endpoint
      trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the
      concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in
      hypertensive patients with diabetes mellitus, whose blood pressure levels were
      inadequately controlled with A II antagonist. This study is different from the
      usual previous studies in that home blood pressures are assessed as indicators of
      evaluation of blood pressure. The ADVANCED-J study may have much influence on
      selection of antihypertensive drugs for treatment in hypertensive patients with
      diabetes mellitus. It is expected to give an important hint for considering the
      validity of selection of antihypertensive drugs from the aspects not only of the
      antihypertensive effect but medical cost-effectiveness.

PMID- 17029632
TI  - Pituitary tumor-transforming gene expression is a prognostic marker for tumor
      recurrence in squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The proto-oncogene pituitary tumor-transforming gene (PTTG) has been
      shown to be abundantly overexpressed in a large variety of neoplasms likely
      promoting neo-vascularization and tumor invasiveness. In this study, we
      investigated a potential role for PTTG mRNA expression as a marker to evaluate
      the future clinical outcome of patients diagnosed with primary cancer of the head
      and neck. METHODS: Tumor samples derived from primary tumors of 89 patients
      suffering from a squamous cell carcinoma were analyzed for PTTG mRNA-expression
      and compared to corresponding unaffected tissue. Expression levels were
      correlated to standard clinico-pathological parameters based on a five year
      observation period. RESULTS: In almost all 89 tumor samples PTTG was found to be
      overexpressed (median fold increase: 2.1) when compared to the unaffected tissue
      specimens derived from the same patient. The nodal stage correlated with PTTG
      transcript levels with significant differences between pN0 (median expression:
      1.32) and pN+ (median expression: 2.12; P = 0.016). In patients who developed a
      tumor recurrence we detected a significantly higher PTTG expression in primary
      tumors (median expression: 2.63) when compared to patients who did not develop a
      tumor recurrence (median expression: 1.29; P = 0.009). Since the median
      expression of PTTG in patients with tumor stage T1/2N0M0 that received surgery
      alone without tumor recurrence was 0.94 versus 3.82 in patients suffering from a
      tumor recurrence (P = 0.006), PTTG expression might provide a feasible mean of
      predicting tumor recurrence. CONCLUSION: Elevated PTTG transcript levels might be
      used as a prognostic biomarker for future clinical outcome (i.e. recurrence) in
      primary squamous cell carcinomas of the head and neck, especially in early stages
      of tumor development.

PMID- 17029634
TI  - Estrogens, selective estrogen receptor modulators, and a selective estrogen
      receptor down-regulator inhibit endothelial production of tissue factor pathway
      inhibitor 1.
AB  - BACKGROUND: Hormone therapy, oral contraceptives, and tamoxifen increase the risk
      of thrombotic disease. These compounds also reduce plasma content of tissue
      factor pathway inhibitor-1 (TFPI), which is the physiological inhibitor of the
      tissue factor pathway of coagulation. The current aim was to study if estrogens
      and estrogen receptor (ER) modulators may inhibit TFPI production in cultured
      endothelial cells and, if so, identify possible mechanisms involved. METHODS:
      Human endothelial cell cultures were treated with 17beta-estradiol (E2), 17alpha
      ethinylestradiol (EE2), tamoxifen, raloxifene, or fulvestrant. Protein levels of
      TFPI in cell media and cell lysates were measured by an enzyme-linked
      immunosorbent assay, and TFPI mRNA levels were assessed by quantitative PCR.
      Expression of ERalpha was analysed by immunostaining. RESULTS: All compounds
      (each in a concentration of 10 nM) reduced TFPI in cell medium, by 34% (E2), 21%
      (EE2), 16% (tamoxifen), and 28% (raloxifene), respectively, with identical
      inhibitory effects on cellular TFPI levels. Expression of TFPI mRNA was
      principally unchanged. Treatment with fulvestrant, which was also associated with
      down-regulation of secreted TFPI (9% with 10 nM and 26% with 1000 nM), abolished
      the TFPI-inhibiting effect of raloxifene, but not of the other compounds.
      Notably, the combination of 1000 nM fulvestrant and 10 nM raloxifene increased
      TFPI secretion, and, conversely, 10 nM of either tamoxifen or raloxifene seemed
      to partly (tamoxifen) or fully (raloxifene) counteract the inhibitory effect of
      1000 nM fulvestrant. The cells did not express the regular nuclear 66 kDa
      ERalpha, but instead a 45 kDa ERalpha, which was not regulated by estrogens or ER
      modulators. CONCLUSION: E2, EE2, tamoxifen, raloxifene, and fulvestrant inhibited
      endothelial production of TFPI by a mechanism apparently independent of TFPI
      transcription.

PMID- 17029633
TI  - The evolutionary radiation of Arvicolinae rodents (voles and lemmings): relative
      contribution of nuclear and mitochondrial DNA phylogenies.
AB  - BACKGROUND: Mitochondrial and nuclear genes have generally been employed for
      different purposes in molecular systematics, the former to resolve relationships
      within recently evolved groups and the latter to investigate phylogenies at a
      deeper level. In the case of rapid and recent evolutionary radiations,
      mitochondrial genes like cytochrome b (CYB) are often inefficient for resolving
      phylogenetic relationships. One of the best examples is illustrated by
      Arvicolinae rodents (Rodentia; Muridae), the most impressive mammalian radiation
      of the Northern Hemisphere which produced voles, lemmings and muskrats. Here, we
      compare the relative contribution of a nuclear marker--the exon 10 of the growth
      hormone receptor (GHR) gene--to the one of the mitochondrial CYB for inferring
      phylogenetic relationships among the major lineages of arvicoline rodents.
      RESULTS: The analysis of GHR sequences improves the overall resolution of the
      Arvicolinae phylogeny. Our results show that the Caucasian long-clawed vole
      (Prometheomys schaposnikowi) is one of the basalmost arvicolines, and confirm
      that true lemmings (Lemmus) and collared lemmings (Dicrostonyx) are not closely
      related as suggested by morphology. Red-backed voles (Myodini) are found as the
      sister-group of a clade encompassing water vole (Arvicola), snow vole
      (Chionomys), and meadow voles (Microtus and allies). Within the latter, no
      support is recovered for the generic recognition of Blanfordimys, Lasiopodomys,
      Neodon, and Phaiomys as suggested by morphology. Comparisons of parameter
      estimates for branch lengths, base composition, among sites rate heterogeneity,
      and GTR relative substitution rates indicate that CYB sequences consistently
      exhibit more heterogeneity among codon positions than GHR. By analyzing the
      contribution of each codon position to node resolution, we show that the apparent
      higher efficiency of GHR is due to their third positions. Although we focus on
      speciation events spanning the last 10 million years (Myr), CYB sequences display
      highly saturated codon positions contrary to the nuclear exon. Lastly, variable
      length bootstrap predicts a significant increase in resolution of arvicoline
      phylogeny through the sequencing of nuclear data in an order of magnitude three
      to five times greater than the size of GHR exon 10. CONCLUSION: Our survey
      provides a first resolved gene tree for Arvicolinae. The comparison of CYB and
      GHR phylogenetic efficiency supports recent assertions that nuclear genes are
      useful for resolving relationships of recently evolved animals. The superiority
      of nuclear exons may reside both in (i) less heterogeneity among sites, and (ii)
      the presence of highly informative sites in third codon positions, that evolve
      rapidly enough to accumulate synapomorphies, but slow enough to avoid
      substitutional saturation.

PMID- 17029636
TI  - Error mapping controller: a closed loop neuroprosthesis controlled by artificial
      neural networks.
AB  - BACKGROUND: The design of an optimal neuroprostheses controller and its clinical
      use presents several challenges. First, the physiological system is characterized
      by highly inter-subjects varying properties and also by non stationary behaviour
      with time, due to conditioning level and fatigue. Secondly, the easiness to use
      in routine clinical practice requires experienced operators. Therefore, feedback
      controllers, avoiding long setting procedures, are required. METHODS: The error
      mapping controller (EMC) here proposed uses artificial neural networks (ANNs)
      both for the design of an inverse model and of a feedback controller. A
      neuromuscular model is used to validate the performance of the controllers in
      simulations. The EMC performance is compared to a Proportional Integral
      Derivative (PID) included in an anti wind-up scheme (called PIDAW) and to a
      controller with an ANN as inverse model and a PID in the feedback loop
      (NEUROPID). In addition tests on the EMC robustness in response to variations of
      the Plant parameters and to mechanical disturbances are carried out. RESULTS: The
      EMC shows improvements with respect to the other controllers in tracking
      accuracy, capability to prolong exercise managing fatigue, robustness to
      parameter variations and resistance to mechanical disturbances. CONCLUSION:
      Different from the other controllers, the EMC is capable of balancing between
      tracking accuracy and mapping of fatigue during the exercise. In this way, it
      avoids overstressing muscles and allows a considerable prolongation of the
      movement. The collection of the training sets does not require any particular
      experimental setting and can be introduced in routine clinical practice.

PMID- 17029635
TI  - QualitySNP: a pipeline for detecting single nucleotide polymorphisms and
      insertions/deletions in EST data from diploid and polyploid species.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are important tools in
      studying complex genetic traits and genome evolution. Computational strategies
      for SNP discovery make use of the large number of sequences present in public
      databases (in most cases as expressed sequence tags (ESTs)) and are considered to
      be faster and more cost-effective than experimental procedures. A major challenge
      in computational SNP discovery is distinguishing allelic variation from sequence
      variation between paralogous sequences, in addition to recognizing sequencing
      errors. For the majority of the public EST sequences, trace or quality files are
      lacking which makes detection of reliable SNPs even more difficult because it has
      to rely on sequence comparisons only. RESULTS: We have developed a new algorithm
      to detect reliable SNPs and insertions/deletions (indels) in EST data, both with
      and without quality files. Implemented in a pipeline called QualitySNP, it uses
      three filters for the identification of reliable SNPs. Filter 1 screens for all
      potential SNPs and identifies variation between or within genotypes. Filter 2 is
      the core filter that uses a haplotype-based strategy to detect reliable SNPs.
      Clusters with potential paralogs as well as false SNPs caused by sequencing
      errors are identified. Filter 3 screens SNPs by calculating a confidence score,
      based upon sequence redundancy and quality. Non-synonymous SNPs are subsequently
      identified by detecting open reading frames of consensus sequences (contigs) with
      SNPs. The pipeline includes a data storage and retrieval system for haplotypes,
      SNPs and alignments. QualitySNP's versatility is demonstrated by the
      identification of SNPs in EST datasets from potato, chicken and humans.
      CONCLUSION: QualitySNP is an efficient tool for SNP detection, storage and
      retrieval in diploid as well as polyploid species. It is available for running on
      Linux or UNIX systems. The program, test data, and user manual are available at
      http://www.bioinformatics.nl/tools/snpweb/ and as Additional files.

PMID- 17029637
TI  - PR genes of apple: identification and expression in response to elicitors and
      inoculation with Erwinia amylovora.
AB  - BACKGROUND: In the past decade, much work has been done to dissect the molecular
      basis of the defence signalling pathway in plants known as Systemic Acquired
      Resistance (SAR). Most of the work has been carried out in model species such as
      Arabidopsis, with little attention paid to woody plants. However within the range
      of species examined, components of the pathway seem to be highly conserved. In
      this study, we attempted to identify downstream components of the SAR pathway in
      apple to serve as markers for its activation. RESULTS: We identified three
      pathogenesis related (PR) genes from apple, PR-2, PR-5 and PR-8, which are
      induced in response to inoculation with the apple pathogen, Erwinia amylovora,
      but they are not induced in young apple shoots by treatment with known elicitors
      of SAR in herbaceous plants. We also identified three PR-1-like genes from apple,
      PR-1a, PR-1b and PR-1c, based solely on sequence similarity to known PR-1 genes
      of model (intensively researched) herbaceous plants. The PR-1-like genes were not
      induced in response to inoculation with E. amylovora or by treatment with
      elicitors; however, each showed a distinct pattern of expression. CONCLUSION:
      Four PR genes from apple were partially characterized. PR-1a, PR-2, PR-5 and PR-8
      from apple are not markers for SAR in young apple shoots. Two additional PR-1
      like genes were identified through in-silico analysis of apple ESTs deposited in
      GenBank. PR-1a, PR-1b and PR-1c are not involved in defence response or SAR in
      young apple shoots; this conclusion differs from that reported previously for
      young apple seedlings.

PMID- 17029638
TI  - Fine motor skills in South African children with symptoms of ADHD: influence of
      subtype, gender, age, and hand dominance.
AB  - BACKGROUND: Motor problems, often characterised as clumsiness or poor motor
      coordination, have been associated with ADHD in addition to the main symptom
      groups of inattention, impulsiveness, and overactivity. The problems addressed in
      this study were: (1) Are motor problems associated with ADHD symptoms, also in
      African cultures? (2) Are there differences in motor skills among the subtypes
      with ADHD symptoms? (3) Are there gender differences? (4) Is there an effect of
      age? (5) Are there differences in performance between the dominant and non
      dominant hand? METHOD: A total of 528 children (264 classified as having symptoms
      of ADHD and 264 matched comparisons) of both genders and from seven different
      South African ethnic groups participated in the study. They were assessed with
      three simple, easy to administer instruments which measure various functions of
      motor speed and eye-hand coordination: The Grooved Pegboard, the Maze
      Coordination Task, and the Finger Tapping Test. The results were analysed as a
      function of subtype, gender, age, and hand dominance. RESULTS: The findings
      indicate that children with symptoms of ADHD performed significantly poorer on
      the Grooved Pegboard and Motor Coordination Task, but not on the Finger Tapping
      Test than their comparisons without ADHD symptoms. The impairment was most severe
      for the subtype with symptoms of ADHD-C (combined) and less severe for the
      subtypes with symptoms of ADHD-PI (predominantly inattentive) and ADHD-HI
      (predominantly hyperactive/impulsive). With few exceptions, both genders were
      equally affected while there were only slight differences in performance between
      the dominant and non-dominant hand. The deficiencies in motor control were mainly
      confined to the younger age group (6-9 yr). CONCLUSION: An association between
      the symptoms of ADHD and motor problems was demonstrated in terms of accuracy and
      speed in fairly complex tasks, but not in simple motor tests of speed. This
      deficiency is found mainly in the children with ADHD-C symptoms, but also to a
      lesser degree in the children with symptoms of ADHD-PI and ADHD-HI.

PMID- 17029639
TI  - Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial
      colorectal cancer predisposition.
AB  - BACKGROUND: The observation that germline mutations in the oxidative DNA damage
      repair gene MUTYH cause colorectal cancer (CRC) provides strong evidence that
      dysregulation of the base excision repair (BER) pathway influences disease
      susceptibility. It is conceivable that germline sequence variation in other BER
      pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also
      contribute to CRC susceptibility. METHODS: To evaluate whether sequence variants
      of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC
      susceptibility alleles, we screened the coding sequence and intron-exon
      boundaries of these genes in 94 familial CRC cases in which involvement of known
      genes had been excluded. RESULTS: Three novel missense variants were identified
      NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in
      188 healthy control DNAs. CONCLUSION: We detected novel germline alterations in
      NEIL2, TDG and UNG patients with CRC. The results suggest a limited role for
      NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 in development of CRC.

PMID- 17029640
TI  - Risk-adjusted cesarean section rates for the assessment of physician performance
      in Taiwan: a population-based study.
AB  - BACKGROUND: Over the past decade, about one-third of all births nationwide in
      Taiwan were delivered by cesarean section (CS). Previous studies in the US and
      Europe have documented the need for risk adjustment for fairer comparisons among
      providers. In this study, we set out to determine the impact that adjustment for
      patient-specific risk factors has on CS among different physicians in Taiwan.
      METHODS: There were 172,511 live births which occurred in either hospitals or
      obstetrics/gynecology clinics between 1 January and 31 December 2003, and for
      whom birth certificate data could be linked with National Health Insurance (NHI)
      claims data, available as the sample for this study. Physicians were divided into
      four equivalent groups based upon the quartile distribution of their crude
      (actual) CS rates. Stepwise logistic regressions were conducted to develop a
      predictive model and to determine the expected (risk-adjusted) CS rate and 95%
      confidence interval (CI) for each physician. The actual rates were then compared
      with the expected CS rates to see the proportion of physicians whose actual rates
      were below, within, or above the predicted CI in each quartile. RESULTS: The
      proportion of physicians whose CS rates were above the predicted CI increased as
      the quartile moved to the higher level. However, more than half of the physicians
      whose actual rates were higher than the predicted CI were not in the highest
      quartile. Conversely, there were some physicians (40 of 258 physicians) in the
      highest quartile who were actually providing obstetric care that was appropriate
      to the risk. When a stricter standard was applied to the assessment of physician
      performance by excluding physicians in quartile 4 for predicting CS rates, as
      many as 60% of physicians were found to have higher CS rates than the predicted
      CI, and indeed, the CS rates of no physicians in either quartile 3 or quartile 4
      were below the predicted CI. CONCLUSION: Overall, our study found that the
      comparison of unadjusted CS rates might not provide a valid reflection of the
      quality of obstetric care delivered by physicians, and may ultimately lead to
      biased judgments by purchasers. Our study has also shown that when we changed the
      standard of quality assessment, the evaluation results also changed.

PMID- 17029641
TI  - Scottish survey of diabetes services for minority ethnic groups.
AB  - BACKGROUND: In the UK, all ethnic minority groups have higher rates of diabetes
      than the general population. Although there have been a number of projects to
      assess diabetic care amongst minority ethnic groups in the United Kingdom, little
      is known about the extent to which the needs of ethnic minority groups are
      actually met by the National Health Service (NHS) Scotland. Therefore we
      conducted this study to understand of the current situation for diabetes care
      available to minority ethnic groups in Scotland. METHODS: We conducted this cross
      sectional study in all health boards in Scotland. A questionnaire was designed
      based on expert comments. It was completed by Local Health Care Cooperatives
      (LHCC) managers, chairs, diabetes specialist nurses and public health
      practitioners. RESULTS: 57 of questionnaires were returned (response rate =
      69.5%). Of these LHCCs, 71% responded that diabetes was part of their LHCC plan.
      However 69% answered that ethnic group was not recorded by community services and
      GPs, and 80% of LHCCs did not monitor trends of complications of diabetes by
      ethnic group. CONCLUSION: Improvement is needed in quality, completeness, and
      availability of minority ethnic group data for diabetes at a national level,
      particularly if NHS Primary Care Organisations are to be responsible for
      providing diabetes care as laid out in the Scottish Diabetes Framework.

PMID- 17029642
TI  - Design factors that influence PCR amplification success of cross-species primers
      among 1147 mammalian primer pairs.
AB  - BACKGROUND: Cross-species primers have been used with moderate success to address
      a variety of questions concerning genome structure, evolution, and gene function.
      However, the factors affecting their success have never been adequately
      addressed, particularly with respect to producing a consistent method to achieve
      high throughput. Using 1,147 mammalian cross-species primer pairs (1089 not
      previously reported), we tested several factors to determine their influence on
      the probability that a given target will amplify in a given species under a
      single amplification condition. These factors included: number of mismatches
      between the two species (the index species) used to identify conserved regions to
      which the primers were designed, GC-content of the gene and amplified region, CpG
      dinucleotides in the primer region, degree of encoded protein conservation,
      length of the primers, and the degree of evolutionary distance between the target
      species and the two index species. RESULTS: The amplification success rate for
      the cross-species primers was significantly influenced by the number of
      mismatches between the two index species (6-8% decrease per mismatch in a primer
      pair), the GC-content within the amplified region (for the dog, GC > or = 50%,
      56.9% amplified; GC<50%, 74.2% amplified), the degree of protein conservation (R2
      = 0.14) and the relatedness of the target species to the index species. For the
      dog, 598 products of 930 primer pairs (64.3%) (excluding primers in which dog was
      an index species) were sequenced and shown to be the expected product, with an
      additional three percent producing the incorrect sequence. When hamster DNA was
      used with the single amplification condition in a microtiter plate-based format,
      510 of 1087 primer pairs (46.9%) produced amplified products. The primer pairs
      are spaced at an average distance of 2.3 Mb in the human genome and may be used
      to produce up to several hundred thousand bp of species-specific sequence.
      CONCLUSION: The most important factors influencing the proportion of successful
      amplifications are the number of index species mismatches, GC-richness of the
      target amplimer, and the relatedness of the target species to the index species,
      at least under the single PCR condition used. The 1147 cross-species primer pairs
      can be used in a high throughput manner to generate data for studies on the
      genetics and genomics of non-sequenced mammalian genomes.

PMID- 17029643
TI  - Dual use of Medicare and the Veterans Health Administration: are there adverse
      health outcomes?
AB  - BACKGROUND: Millions of veterans are eligible to use the Veterans Health
      Administration (VHA) and Medicare because of their military service and age. This
      article examines whether an indirect measure of dual use based on inpatient
      services is associated with increased mortality risk. METHODS: Data on 1,566 self
      responding men (weighted N = 1,522) from the Survey of Assets and Health Dynamics
      among the Oldest Old (AHEAD) were linked to Medicare claims and the National
      Death Index. Dual use was indirectly indicated when the self-reported number of
      hospital episodes in the 12 months prior to baseline was greater than that
      observed in the Medicare claims. The independent association of dual use with
      mortality was estimated using proportional hazards regression. RESULTS: 96 (11%)
      of the veterans were classified as dual users. 766 men (50.3%) had died by
      December 31, 2002, including 64.9% of the dual users and 49.3% of all others, for
      an attributable mortality risk of 15.6% (p < .003). Adjusting for demographics,
      socioeconomics, comorbidity, hospitalization status, and selection bias at
      baseline, as well as subsequent hospitalization for ambulatory care sensitive
      conditions, the independent effect of dual use was a 56.1% increased relative
      risk of mortality (AHR = 1.561; p = .009). CONCLUSION: An indirect measure of
      veterans' dual use of the VHA and Medicare systems, based on inpatient services,
      was associated with an increased risk of death. Further examination of dual use,
      especially in the outpatient setting, is needed, because dual inpatient and dual
      outpatient use may be different phenomena.

PMID- 17029644
TI  - An instrument to measure job satisfaction of nursing home administrators.
AB  - BACKGROUND: The psychometric properties of the nursing home administrator job
      satisfaction questionnaire (NHA-JSQ) are presented, and the steps used to develop
      this instrument. METHODS: The NHA-JSQ subscales were developed from pilot survey
      activities with 93 administrators, content analysis, and a research panel. The
      resulting survey was sent to 1,000 nursing home administrators. Factor analyses
      were used to determine the psychometric properties of the instrument. RESULTS: Of
      the 1,000 surveys mailed, 721 usable surveys were returned (72 percent response
      rate). The factor analyses show that the items were representative of six
      underlying factors (i.e., coworkers, work demands, work content, work load, work
      skills, and rewards). CONCLUSION: The NHA-JSQ represents a short,
      psychometrically sound job satisfaction instrument for use in nursing homes.

PMID- 17029645
TI  - A missense mutation in PMEL17 is associated with the Silver coat color in the
      horse.
AB  - BACKGROUND: The Silver coat color, also called Silver dapple, in the horse is
      characterized by dilution of the black pigment in the hair. This phenotype shows
      an autosomal dominant inheritance. The effect of the mutation is most visible in
      the long hairs of the mane and tail, which are diluted to a mixture of white and
      gray hairs. Herein we describe the identification of the responsible gene and a
      missense mutation associated with the Silver phenotype. RESULTS: Segregation data
      on the Silver locus (Z) were obtained within one half-sib family that consisted
      of a heterozygous Silver colored stallion with 34 offspring and their 29 non
      Silver dams. We typed 41 genetic markers well spread over the horse genome,
      including one single microsatellite marker (TKY284) close to the candidate gene
      PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the
      Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in
      Silver and non-Silver horses revealed a missense mutation in exon 11 changing the
      second amino acid in the cytoplasmic region from arginine to cysteine
      (Arg618Cys). This mutation showed complete association with the Silver phenotype
      across multiple horse breeds, and was not found among non-Silver horses with one
      clear exception; a chestnut colored individual that had several Silver offspring
      when mated to different non-Silver stallions also carried the exon 11 mutation.
      In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14
      breeds were tested for the exon 11 mutation. One additional mutation located in
      intron 9, only 759 bases from the missense mutation, also showed complete
      association with the Silver phenotype. However, as one could expect to find
      several non-causative mutations completely associated with the Silver mutation,
      we argue that the missense mutation is more likely to be causative. CONCLUSION:
      The present study shows that PMEL17 causes the Silver coat color in the horse and
      enable genetic testing for this trait.

PMID- 17029646
TI  - Normative data and discriminative properties of short form 36 (SF-36) in Turkish
      urban population.
AB  - BACKGROUND: SF-36 has been both translated into different languages and adapted
      to different cultures to obtain comparable data on health status internationally.
      However there have been only a limited number of studies focused on the
      discriminative ability of SF-36 regarding social and disease status in developing
      countries. The aim of this study was to obtain population norms of the short form
      36 (SF-36) health survey and the association of SF-36 domains with demographic
      and socioeconomic variables in an urban population in Turkey. METHODS: A cross
      sectional study. Face to face interviews were carried out with a sample of
      households. The sample was systematically selected from two urban Health
      Districts in Izmir, Turkey. The study group consisted of 1,279 people selected
      from a study population of 46,290 people aged 18 and over. RESULTS: Internal
      consistencies of the scales were high, with the exception of mental health and
      vitality. Physical health scales were associated with both age and gender. On the
      other hand, mental health scales were less strongly associated with age and
      gender. Women reported poorer health compared to men in general. Social risk
      factors (employment status, lower education and economic strain) were associated
      with worse health profiles. The SF-36 was found to be capable of discriminating
      disease status. CONCLUSION: Our findings, cautiously generalisable to urban
      population, suggest that the SF-36 can be a valuable tool for studies on health
      outcomes in Turkish population. SF-36 may also be a promising measure for
      research on health inequalities in Turkey and other developing countries.

PMID- 17029649
TI  - Biological imaging using secondary ions.
AB  - Biological materials are morphologically and chemically complex. A quantitative
      imaging tool is now available that can produce chemical, and even metabolic,
      information from morphological features as small as a few nanometers.

PMID- 17029648
TI  - HIV prevalence and factors associated with HIV infection among male injection
      drug users under 30: a cross-sectional study in Long An, Vietnam.
AB  - BACKGROUND: Sufficient targeted HIV prevention activities aiming at reducing HIV
      transmission within and from an extremely marginalized population of injection
      drug users (IDUs) must urgently and efficiently be implemented in Vietnam. This
      study was conducted to facilitate the development of such activities by
      describing transmission risks of young IDUs and evaluating factors in association
      with HIV infection. METHODS: Thirty clusters were selected from 29 hotspot
      communes in Long An province by probability proportional to size (PPS) sampling
      method. The snowball technique was used for enrolling participants in each
      cluster. The cross-sectional association of factors obtained during direct
      structured interviews to 248 male IDUs aged 14 to 29 years old and with their HIV
      test results were examined. RESULTS: The HIV prevalence among the studied IDUs
      was 32%. Age range of 18-20 years old, low educational level, sharing injection
      equipment or injection drug use in the other cities were independently associated
      with HIV serostatus in the multivariate analysis. Sexual behaviors did not differ
      between HIV-positive and -negative IDUs. Among HIV seropositive IDUs who had
      sexual contact with primary (n = 37), casual (n = 6), and commercial (n = 15)
      partners, only 5.4% (n = 2), 33.3% (n = 2), and 46.7% (n = 7), respectively,
      responded that they had used condoms every time. CONCLUSION: About one-third of
      young IDUs aged less than 30 identified in the hotspot communes in Long An,
      Vietnam was found to be infected with HIV, and socio-demographic and injection
      related factors might account for the infection risk. Prevailing risky sexual
      behavior of this extremely marginalized population highlights the need to reduce
      their high transmission risks as a public health priority.

PMID- 17029651
TI  - Recently published papers: pneumonia, hypothermia and the elderly.
AB  - Pneumonia (hospital-acquired and community-acquired) is commonly encountered in
      intensive care. Several papers recently published on this subject have shed more
      light on different aspects of this important topic. Hypothermia has been shown to
      improve post-arrest outcome, but how often do we use it? And finally, several
      papers have recently appeared in the journals related to the admission of the
      elderly to the critical care area and their outcome.

PMID- 17029652
TI  - Drotrecogin alfa (activated): down and not out, but not really in either.

PMID- 17029653
TI  - Evidence-based medicine: classifying the evidence from clinical trials--the need
      to consider other dimensions.
AB  - The current approach to assessing the quality of evidence obtained from clinical
      trials focuses on three dimensions: the quality of the design (with double
      blinded randomised controlled trials representing the highest level of such
      design); the statistical power (beta) and the level of significance (alpha).
      While these aspects are important, we argue that other significant aspects of
      trial quality impinge upon the truthfulness of the findings: biological
      plausibility, reproducibility and generalisability. We present several recent
      studies in critical care medicine where the design, beta and alpha components of
      the study are seemingly satisfactory but where the aspects of biological
      plausibility, reproducibility and generalisability show serious limitations.
      Accordingly, we argue for more reflection, definition and consensus on these
      aspects of the evaluation of evidence.

PMID- 17029647
TI  - Human malarial disease: a consequence of inflammatory cytokine release.
AB  - Malaria causes an acute systemic human disease that bears many similarities, both
      clinically and mechanistically, to those caused by bacteria, rickettsia, and
      viruses. Over the past few decades, a literature has emerged that argues for most
      of the pathology seen in all of these infectious diseases being explained by
      activation of the inflammatory system, with the balance between the pro and anti
      inflammatory cytokines being tipped towards the onset of systemic inflammation.
      Although not often expressed in energy terms, there is, when reduced to
      biochemical essentials, wide agreement that infection with falciparum malaria is
      often fatal because mitochondria are unable to generate enough ATP to maintain
      normal cellular function. Most, however, would contend that this largely occurs
      because sequestered parasitized red cells prevent sufficient oxygen getting to
      where it is needed. This review considers the evidence that an equally or more
      important way ATP deficiency arises in malaria, as well as these other infectious
      diseases, is an inability of mitochondria, through the effects of inflammatory
      cytokines on their function, to utilise available oxygen. This activity of these
      cytokines, plus their capacity to control the pathways through which oxygen
      supply to mitochondria are restricted (particularly through directing
      sequestration and driving anaemia), combine to make falciparum malaria primarily
      an inflammatory cytokine-driven disease.

PMID- 17029654
TI  - Combined functional task practice and dynamic high intensity resistance training
      promotes recovery of upper-extremity motor function in post-stroke hemiparesis: a
      case study.
AB  - BACKGROUND AND PURPOSE: Weakness is a significant impairment in persons with post
      stroke hemiparesis, yet traditional clinical perspectives caution against
      strengthening in neurological populations. Significant correlations between
      weakness and functional movement have been demonstrated, however, a clear
      relationship between increased strength and functional improvement has been
      elusive. This case study describes a combined program of dynamic, high-intensity
      resistance training and functional task practice for the upper-extremity in adult
      hemiparesis. CASE DESCRIPTION: The patient was a 65-year-old, right hand dominant
      woman who presented to the Neural Control of Movement Laboratory at the Palo Alto
      VA Rehabilitation Research and Development Center 16 weeks following clipping of
      an unruptured aneurysm with consequent dense right hemiparesis. She received 7
      weeks of acute rehabilitation according to CARF guidelines (ie, at least 3 hours
      of two or more disciplines, 6 days per week). Her baseline research evaluation
      revealed significant upperextremity deficits at the ICF body structure/function
      level including: weakness, shoulder pain, mild resistance to passive movement,
      and need for moderate to maximal assistance in many activities of daily living
      including bathing and dressing. The Stroke Impact Scale score reporting her
      perspective indicated she had recovered from her stroke only 50%. The hybrid
      resistance training-functional task practice intervention, detailed in this
      report, was delivered 3 times per week for 6 weeks with each session lasting
      75:00. OUTCOMES: The subject revealed marked improvements in isometric and
      dynamic force production in 5 key upper-extremity actions: elbow flexion, elbow
      extension, shoulder flexion, shoulder abduction, and shoulder external rotation.
      Strength gains were accompanied by increased EMG activation immediately
      postintervention and by a combination of increased activation and apparent
      hypertrophic effects at 6 month follow up. Marked improvements were noted in all
      clinical and functional measures and in an elbow trajectorytracking task which
      served as a surrogate measure of motor control. DISCUSSION: Improvements in
      strength and positive outcome effects at the physiological, clinical, and
      functional levels were observed in this subject following the experimental hybrid
      upper-extremity rehabilitation intervention described. Importantly, no
      deleterious effects were observed including exacerbation of spasticity or
      musculoskeletal compromise. Observations of improved EMG activation in this case
      study suggest that improvements in motor activation underlie these strength gains
      and can likely be attributed to working at a high intensity level.

PMID- 17029655
TI  - Optimal movement variability: a new theoretical perspective for neurologic
      physical therapy.
AB  - Variability is a natural and important feature of human movement. Using existing
      theoretical frameworks as a foundation, we propose a new model to explain
      movement variability as it relates to motor learning and health. We contend that
      mature motor skills and healthy states are associated with an optimal amount of
      movement variability. This variability also has form and is characterized by a
      chaotic structure. Less than optimal movement variability characterizes
      biological systems that are overly rigid and unchanging, whereas greater than
      optimal variability characterizes systems that are noisy and unstable. Both
      situations characterize systems that are less adaptable to perturbations, such as
      those associated with abnormal motor development or unhealthy states. From our
      perspective, the goal of neurologic physical therapy should be to foster the
      development of this optimal amount of movement variability by incorporating a
      rich repertoire of movement strategies. The development of such a repertoire can
      be enhanced by incorporating a multitude of experiences within the therapeutic
      milieu. Promoting complex variation in human movement allows either motor
      development or the recovery of function after injury not to be hard coded, but
      determined instead by the active engagement of the individual within their
      environment. Measurement tools derived from nonlinear dynamics that characterize
      the complexity of movement variability provide useful means of testing these
      propositions. To illustrate, we present 2 clinical case studies, one pediatric
      and one adult, where we applied our theoretical framework to measuring change in
      postural control.

PMID- 17029656
TI  - Combined task-specific training and strengthening effects on locomotor recovery
      post-stroke: a case study.
AB  - BACKGROUND AND PURPOSE: Task-specific and strength training have demonstrated
      efficacy as therapeutic interventions poststroke. The intent of this case study
      is to describe outcomes associated with a therapy program that combines task
      specific and strength training in an individual post-stroke and to discuss some
      possible mechanisms and modulating factors that may affect post-stroke neurologic
      recovery and responsiveness to intervention. CASE DESCRIPTION: The participant
      was a 38-year-old female with right middle cerebral artery stroke, evaluated 15
      months postonset. She ambulated independently with an ankle-foot orthosis and
      straight cane. Her free and fast overground velocity was 0.50 m/s and 0.62 m/s,
      respectively. Body-weight supported treadmill training and a limb-loaded cycling
      exercise were alternated over 24 treatments sessions (4 times/wk for 6 wks).
      Measurements were taken pre-, post-treatment, and at a 6-mo follow-up.
      Instrumented gait and motion analysis with fine-wire EMG recording of LE muscle
      activity occurred pre- and post-treatment. OUTCOMES: Post-treatment, walking
      speed increased 18% for free--(0.59 m/ s) and 14.4% for fast-velocity (0.71 m/s);
      6-min walking distance increased 4% (184.4 m). At 6-mos, continued improvements
      in all walking outcomes were evident. Gait and motion analysis revealed that
      functional locomotor recovery was associated with increases in magnitude of
      paretic leg gluteus maximus and gluteus medius activation during gait. Motion
      analysis confirmed an increase of hip and knee extension motions throughout
      stance and swing. DISCUSSION: For the person in this case clinically meaningful
      changes in walking function were associated with a combined therapeutic program
      that included both task-specific and LE strength training. Possible mechanisms
      associated with response to therapy were related to improved motor unit
      activation associated with increased strength in key muscles used in gait.

PMID- 17029657
TI  - A perception-action framework for physical therapy for persons with neurologic
      dysfunction: use of therapeutic affordance and unitless ratio.
AB  - BACKGROUND AND PURPOSE: Our goal through this case study is to introduce the
      reader to the perception-action framework (PAF) for human action and the
      application of this framework to examination and treatment in physical therapy.
      We define the concepts of affordance, constraints, and emergent action as example
      concepts in the PAF and then apply these concepts to examination and treatment in
      physical therapy through the use of unitless ratios. At critical values of these
      ratios, the coordination pattern used or the action taken undergoes a shift. We
      offer examples that contrast some of the unique aspects of the PAF to approaches
      such as the hierarchical or motor program approaches that primarily focus on the
      nervous system influence on the motor aspects of human action. CASE DESCRIPTION:
      This principled approach to examination and treatment can be used with patients
      of all ages. Here, we provide the case of a 59-year-old, right handed male status
      post acute, embolic stroke with right posterior cerebral artery (PCA) and right
      middle cerebral artery (MCA) territory infarcts. The PAF and the specific use of
      unitless ratios for examination and treatment of reaching and grasping are
      detailed. OUTCOMES: Research supports that the unitless ratio created from the
      size of a cube to the range of motion of the index finger-thumb aperture defines
      the boundaries for the shift between a 1 handed and a 2 handed reach regardless
      of age. These boundary conditions are used to examine the subjects grasping
      abilities and the emergent reaching coordination pattern that occurs as cube size
      is varied. SUMMARY: Therapeutic use of the PAF requires new examination and
      intervention strategies predicated on the development of unitless ratios for
      functional human actions. Key Words: perception-action; stroke, motor control,
      unitless ratio.

PMID- 17029658
TI  - Attempting to improve function and quality of life using the FTM Protocol: case
      report.
AB  - BACKGROUND AND PURPOSE: The Functional Tone Management (FTM) arm training program
      uses repetitive task practice, stretching, and electrical stimulation as patients
      with moderate upper extremity hemiparesis wear a dynamic hand orthosis to retrain
      grasp and release of objects. The case study quantitatively evaluates the extent
      to which FTM training improved function and quality of life in a patient who met
      criteria for which the device was intended. CASE DESCRIPTION: The participant, a
      44-year-old male in the chronic stage of stroke recovery with moderate right
      upper extremity motor impairment, was trained for 10 days over a 2-week period by
      a licensed clinician with extensive experience in FTM training methods.
      Measurements were taken over 3 baseline visits, then immediately preintervention,
      postintervention, and at a 3-month follow-up. The outcome measures, following the
      International Classification of Functioning, Disability, and Health (ICF) Model,
      included the: Fugl-Meyer assessment (FMA) (upper extremity portion), UE range of
      motion (ROM), Modified Ashworth scale, Wolf Motor Function Test (WMFT), and the
      Motor Activity Log (MAL). Health related quality of life was measured using the
      Stroke Impact Scale (SIS). OUTCOMES: The participant showed limited gains in
      upper extremity function immediately postintervention. Increases in AROM occurred
      in forearm supination and wrist flexion and extension, but no improvements were
      noted in finger ROM. A slight decrease in tone was found in forearm pronators (1
      to 0) and wrist flexors (1+ to 1). WMFT values for the more affected upper
      extremity did not change immediately after training, but a 17% reduction in time
      occurred at follow-up, with improvements, most notably in the tasks of lifting a
      pencil and lifting a paper clip. No changes occurred in UE-FMA scores immediately
      following the intervention, however, a 17% improvement was measured at followup.
      A slight improvement in MAL scores was noted but not to a level of independent
      functional use of the impaired upper extremity. SIS scores improved in the
      domains of strength, communication, mobility, social participation, hand
      recovery, and overall physical component, while decreases were seen in the
      ADL/IADL, hand function, emotion, and cognitive domains. DISCUSSION: The case
      study indicates that for this patient with chronic, moderate upper extremity
      impairment following stroke, a 2-week FTM training regimen resulted in modest
      changes occurring as a decrease in impairment, with functional improvement and
      improved quality of life. Further investigation of the innovative training
      program should be undertaken before the efficacy of its use can be ascertained
      amongst patients with limitations comparable to the participant.

PMID- 17029659
TI  - Perspective: impact of the IIISTEP conference on clinical practice.
AB  - In July 2005, physical therapy clinicians, educators, and researchers gathered
      for the IIISTEP (Symposium on Translating Evidence to Practice) conference. The
      purpose of IIISTEP was to link research and clinical practice through the
      exchange of ideas and research findings between scientists and clinicians. This
      paper represents the personal perspective of a group of colleagues who attended
      IIISTEP as clinicians/educator teams. The purpose of this paper is to illustrate
      how information from IIISTEP has challenged our existing concepts regarding
      physical therapy practice and begun to alter our clinical practice. Some key
      concepts presented by scientists and clinicians at IIISTEP are reviewed including
      current perspectives on neuroplasticity and frameworks for considering function,
      health, and the disablement process. Considerations for clinical application are
      outlined. Patient cases are used to illustrate how integration of this
      information has altered our approach to patient management.

PMID- 17029660
TI  - Biosocial and nutritional effects on body composition in young adults from
      Wroclaw, Poland.
AB  - This work concerns the questions if and to what extent social variables past and
      present, and actual sports activity and nutritional and smoking habits, have an
      influence on body compartment indices, and how this differs between female and
      male medical students from Wroclaw, Poland. Backward stepwise regression was
      applied to four dependent variables, i.e. Body Mass Index (BMI), %Fat Mass (%FM),
      Extracellular Water/Intracellular Water Index (100 x ECW/ICW) and Body Cell Mass
      Index (BCMI=BCM/height2), and for eighteen independent variables including
      nutrition, parents' social status, smoking and sports activity. Females ate meat
      less frequently and fruit and vegetables more often, and drank beer less
      frequently but milk more often than did male students. It seems that there exists
      some effect on fat accumulation resulting from difference in nutrition between
      females and males. The results may be interpreted in terms of a parental gender
      effect on body composition of children associated with different conditions of
      life and nutrition in childhood and youth for female and male students in
      Wroclaw.

PMID- 17029661
TI  - It's all in the timing: coital frequency and fertility awareness-based methods of
      family planning.
AB  - Fertility awareness-based methods of family planning help women to identify the
      days of the cycle they should avoid unprotected intercourse to prevent pregnancy.
      Therefore using fertility awareness-based methods influences the timing of sexual
      activity, which may affect the nature of the sexual relationship. Data are used
      from the clinical trials of two fertility awareness-based methods--the Standard
      Days Method and the TwoDay Method--to determine the frequency and timing of
      intercourse during the cycle, and the determinants of coital frequency. The mean
      coital frequency of study participants was similar to that reported by users of
      other methods. Results suggest that coital frequency increases with consecutive
      cycles of method use. At the same time the frequency of intercourse during the
      identified fertile days and during menses decreases. This evidence implies a
      behavioural change as couples get more experience using their method and
      communicating about the fertile days. Coital frequency was also influenced by the
      method used and by the study sites. Potential differences between the methods and
      sites that may contribute to this effect are discussed.

PMID- 17029662
TI  - Disagreement in spousal reports of current contraceptive use in sub-Saharan
      Africa.
AB  - Contraceptive prevalence is a key variable estimated from Demographic and Health
      Surveys. But the prevalence estimated from reports of husbands differs widely
      from that estimated for wives. In this research, using data from six Demographic
      and Health Surveys of sub-Saharan Africa, reports from spouses in monogamous
      couples with no other reported sex partners in the recent period are examined.
      Agreement ranged from 47% to 82%, but among couples in which one or both reported
      use, the 'both' category represented less than half in all nations except
      Zimbabwe. Husbands generally had higher reports of condoms, periodic abstinence
      and pills but fewer reports of the IUD, injections and female sterilization.
      Either discussion of family planning with the spouse and/or higher socioeconomic
      status was associated with agreement in most of the surveys. Ambiguities in the
      survey question regarding current use need to be reduced, perhaps with an added
      probe question for non-permanent methods.

PMID- 17029663
TI  - Age dependent increase in early resistance of mice to Mycobacterium tuberculosis
      is associated with an increase in CD8 T cells that are capable of antigen
      independent IFN-gamma production.
AB  - The lungs of naive 18-month-old mice contain an abundant resident population of
      CD8 T cells that express typical markers of memory, express elevated levels of
      Th1 cytokine receptors on their surface, and are capable of non-specific IFN
      gamma production in response to a Th1 cytokine cocktail. In this study we
      characterize this population of CD8 T cells in the lungs and spleens of mice with
      increasing age. In general, the proportion of CD8 T cells expressing markers of
      memory and Th1 cytokine receptors increased with age. The enhanced ability of CD8
      T cells to produce IFN-gamma in an antigen independent manner followed this
      pattern as well, beginning to increase between 6 and 12 months of age.
      Interestingly, the phenotypic and functional age-related changes in CD8 T cells
      were also associated with a progressive age-related increase in early resistance
      to Mycobacterium tuberculosis. Taken together, these data suggest that as mice
      age a population of memory CD8 T cells, that are capable of contributing to
      innate immune responses to M. tuberculosis, gradually emerges and could be
      relevant for developing strategies to enhance immunity in the elderly.

PMID- 17029664
TI  - Effect of age on skeletal muscle myofibrillar mRNA abundance: relationship to
      myosin heavy chain protein synthesis rate.
AB  - Age-related changes in myosin heavy chain (MHC) phenotype impact both the
      quantity and functional character of skeletal muscle. The present study was
      undertaken to examine the hypothesis that age-related changes in MHC mRNA
      abundance underlie alterations in protein synthesis rates and content. We
      measured the abundance of mRNA for MHC isoforms (MHC I, MHC IIa, IIx) and actin
      by RT-PCR in 6 young (mean +/- SE; 29 +/- 3) and 12 elderly (73 +/- 1 yr; P<0.01)
      volunteers and examined their association to MHC protein synthesis rates and
      their respective protein products. We found no differences between young and
      elderly volunteers in MHC isoform or actin transcript levels. Because of the
      absence of age effects, data were pooled for correlation analyses. Although total
      MHC mRNA levels were not related to MHC fractional synthesis rates, the relative
      abundance of MHC I and MHC IIa mRNA were positively (r = 0.450; P = 0.06) and
      negatively (r = -0.493; P<0.05) associated with MHC protein synthesis rates,
      respectively. MHC mRNA levels were positively correlated to their respective
      protein products (range of r-values: 0.551-0.727; P<0.05 to P<0.01), but were not
      related to skeletal muscle IGF-I mRNA abundance, circulating IGF-I or markers of
      immune activation. Our results argue against the notion that changes in MHC
      protein synthesis rates with age are related to altered MHC mRNA abundance,
      although our findings do suggest that possibility that individual variability in
      MHC protein synthesis rates is related to the relative abundance of MHC I versus
      MHC IIa transcripts.

PMID- 17029665
TI  - Elevated caspase and AIF gene expression correlate with progression of sarcopenia
      during aging in male F344BN rats.
AB  - To establish the relationship between the progression of sarcopenia and apoptosis
      we examined apoptotic gene expression in plantaris muscles (Pl) from 8 mo old
      (n=8), 30 mo old (n=8) and 35 mo old (n=6) male rats by real-time PCR. Pl mass
      declined from 368 +/- 7 mg at 8 mo to 333 +/- 7 mg at 30 mo (P<0.05) and 210 +/-
      15 mg at 35 mo of age (P<0.05). BAX, Bcl-2, and Apaf-1 expression decreased by 62
      74% at 30 mo and by 90-96% at 35 mo of age (all P<0.05 vs 8 mo old). In contrast,
      the expression of Caspases 3, 8, and 9 and AIF increased 3- to 5-fold at 30 mo
      (NS) and 7- to 50-fold at 35 mo of age (P<0.05). There were significant (P<0.05)
      correlations between Pl mass and Caspase 3 (r(2)=-0.60), Caspase 9 (r(2)=-0.58),
      Caspase 8 (r(2)=-0.50), and AIF (r(2)=-0.48). Thus, our results show that the
      expression of some genes involved in apoptosis increase with aging in Pl and
      correlate with progression of sarcopenia (Caspase 3, Caspase 9, Caspase 8, and
      AIF), whereas others decline with aging (BAX, Bcl-2, and Apaf-1).

PMID- 17029666
TI  - Radionuclides in marine macroalgae from Amchitka and Kiska Islands in the
      Aleutians: establishing a baseline for future biomonitoring.
AB  - Levels of radionuclides in seven species of marine brown algae and Ulva were
      determined to establish a baseline for the Northern Pacific Ocean/Bering Sea
      (Aleutian Islands). There were differences in levels among algal species and
      locations (Amchitka Island vs Kiska Island). No values were above the minimum
      detectable activity (MDA) level for (137)Cs, (129)I, (60)Co, (152)Eu, (90)Sr, and
      (99)Tc. There were interspecific differences in some radionuclides: Ulva lactuca
      (=Ulva fenestrata) had the highest levels of (241)Am, Alaria fistulosa had the
      highest levels of (239,240)Pu, and Fucus distichus (=Fucus gardneri) had the
      highest levels of (234)U, (235)U, and (238)U. However, levels of all
      radionuclides were generally low and near the MDA for all isotopes. Although
      Amchitka Island had higher levels of (239,240)Pu than Kiska, the differences were
      very small and not significant biologically. The data indicate that algae can be
      useful bioindicators of actinides because they accumulate them at very low
      environmental levels, allowing them to provide early warning of any potential
      seepage of radionuclides into the marine environment. Further, the data indicate
      that some species (the intertidal Fucus) are better accumulators than others, and
      these should be used as bioindicators in future monitoring schemes.

PMID- 17029667
TI  - Speciation of 210Po and 210Pb in air particulates determined by sequential
      extraction.
AB  - Speciation of (210)Po and (210)Pb in air particulates of two Syrian phosphate
      sites with different climate conditions has been studied. The sites are the mines
      and Tartous port at the Mediterranean Sea. Air filters were collected during
      September 2000 until February 2002 and extracted chemically using different
      selective fluids in an attempt to identify the different forms of these two
      radionuclides. The results have shown that the inorganic and insoluble (210)Po
      and (210)Pb (attached to silica and soluble in mineral acids) portion was found
      to be high in both sites and reached a maximum value of 94% and 77% in the mine
      site and Tartous port site, respectively. In addition, only 24% of (210)Pb in air
      particulates was found to be associated with organic materials probably produced
      from the incomplete burning of fuel vehicle and similar activities. Moreover, the
      (210)Po/(210)Pb activity ratio in air particulates was higher than that in all
      samples at both sites and varied between 3.85 in November 2000 at Tartous port
      site and 20 in April 2001 at the mine area. These activity ratios were also
      higher than the natural levels. The (210)Po/(210)Pb activity ratio was also
      determined in each portion resulting from the selective extraction and found to
      be higher than that in most samples. The sources of (210)Po excess in these
      portions are discussed. Soil suspension, which is common in the dry climate
      dominant in the area, sea water spray and heating of phosphate ores were
      considered; polonium is more volatile than the lead compounds at even moderate
      temperature. Furthermore, variations in the chemical forms of (210)Po and (210)Pb
      during the year were also investigated. However, the results of this study can
      also be utilized for dose assessment to phosphate industry workers.

PMID- 17029668
TI  - Evaluation of paclitaxel rearrangement involving opening of the oxetane ring and
      migration of acetyl and benzoyl groups.
AB  - The stability of drug is a critical factor in quality control, drug efficacy,
      safety, storage, and production conditions. The rearrangement of paclitaxel,
      which involves opening of the oxetane ring and migration of acetyl group occurred
      on heating a powder of purified paclitaxel. Subsequently, the unusual migration
      of benzoyl groups progressed rapidly in organic solvents. These rearrangement
      derivatives were isolated carefully. The structures of the intermediate
      derivative A and the product derivative B were confirmed using (1)H NMR, high
      performance liquid chromatography (HPLC), and mass spectrometry. We proposed the
      rearrangement pathway here for the first time. Neither derivative exhibited
      bioactivity in SKOV3 (ovarian cancer) or MDA-MB-435 (breast cancer) cell culture
      assays.

PMID- 17029669
TI  - Rapid determination of total solanesol in tobacco leaf by ultrasound-assisted
      extraction with RP-HPLC and ESI-TOF/MS.
AB  - A reliable and rapid method based on high-performance liquid chromatography (HPLC
      UV) and positive ion electrospray-time of flight mass spectrometry (ESI-TOF/MS)
      has been developed for the characterization and quantification of solanesol in
      extracts of tobacco leaves from different sources. The solanesol was extracted
      from tobacco leaf via saponification and ultrasonic-assist extraction, and the
      extraction conditions were optimized. The HPLC conditions are as following:
      Hypersil C(4) (4.6 mm x 150 mm, 5 microm) column, acetonitrile and water as
      mobile phase, flow-rate is 0.8 ml/min, detection length of UV is 202 nm,
      injection volume is 10 microl. The results indicated that the developed HPLC
      method is simple, sensitive and reliable for the determination of solanesol in
      tobacco leaves with a linear dynamic range of 3.65-4672 ng, a detection limit of
      1.83 ng, and an average recovery of 98.7%. The method has been applied to analyze
      and compare different tobacco samples. The results show that the solanesol
      content in samples of different geographic locations varies widely from 0.20 to
      1.50%. When different parts of the tobacco plant are compared, the top parts of
      the leaves are more abundant in solanesol content than those of lower parts.

PMID- 17029670
TI  - LC-MS/MS method for simultaneous determination of viramidine and ribavirin levels
      in monkey red blood cells.
AB  - A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been developed for the simultaneous determinations of total viramidine
      (viramidine, viramidine monophosphate, viramidine diphosphate, and viramidine
      triphosphate) and total ribavirin (ribavirin, ribavirin monophosphate, ribavirin
      diphosphate, and ribavirin triphosphate) in monkey red blood cells (RBC). The
      method involves the addition of internal standards and perchloric acid,
      conversion of viramidine or ribavirin phosphorylated metabolites to viramidine or
      ribavirin, purification with an aminopropyl (NH(2)) solid phase extraction (SPE)
      cartridge, and LC-MS/MS analysis. The MS/MS is selected to monitor m/z 245-->113,
      250-->113, 244-->112, and 249-->112 for ribavirin, [(13)C]ribavirin, viramidine,
      and [(13)C]viramidine, respectively, using positive electrospray ionization. The
      calibration curves are linear over a concentration range of 100-10,000 ng/mL
      (0.412-41.2 microM) with a lower limit of quantification (LLOQ) of 100 ng/mL for
      both compounds. Mean inter-assay recoveries for ribavirin are 101%, 98.9%, and
      96.0%, with coefficient of variance (%CV) values between 1.95 and 4.50% for 100,
      1000, and 10,000 ng/mL quality control (QC) samples, respectively. Mean inter
      assay recoveries for viramidine are 96.3%, 101%, and 102%, with coefficient of
      variation (%CV) values between 3.61 and 7.22%, for 100, 1000, and 10,000 ng/mL QC
      samples, respectively. Over-curve dilution QC at 400 microg/mL (1639 microM) for
      both viramidine and ribavirin are used to ensure the dilution accuracy (25 X
      dilutions) for monkey samples. The method has been used to simultaneously
      determine the total concentrations of ribavirin and viramidine in monkey RBC
      following 5, 15, and 36 weeks dosing of viramidine or ribavirin (60 mg/kg). The
      concentrations of total ribavirin following ribavirin dosing are 1242 microM at
      week 5, 1257 microM at week 15, and 1146 microM at week 36. The concentrations of
      total ribavirin following viramidine dosing are 634 microM at week 5, 716 microM
      at week 15, and 683 microM at week 36. Only small amounts of viramidine are
      detected in RBC following viramidine dosing, 7.80 microM at week 5, 6.63 microM
      at week 15, and 10.4 microM at week 36. The results suggest that ribavirin levels
      in RBC were at steady state at week 5 of ribavirin or viramidine dosing. At
      steady state, ribavirin levels in RBC are approximately 2x after ribavirin dosing
      than viramidine dosing. The relatively small percentage of viramidine in RBC
      suggests that viramidine either poorly penetrated into RBC or was extensively
      converted to ribavirin following entry into RBC.

PMID- 17029671
TI  - Metabolomic discrimination of different grades of pine-mushroom (Tricholoma
      matsutake Sing.) using 1H NMR spectrometry and multivariate data analysis.
AB  - Metabolomic analysis of raw and cooked pine-mushrooms (Tricholoma matsutake
      Sing.) of different grades was performed using (1)H nuclear magnetic resonance
      (NMR) spectrometry and principal component analysis (PCA). PCA of the (1)H NMR
      spectra of aqueous fractions allowed different grades of raw pine-mushroom to be
      discriminated by a combination of principal component (PC) 1 and PC 2, which
      accounted cumulatively for 94.1% of the variation in all variables. The major
      peaks in the (1)H NMR spectra that contributed to discrimination of raw mushrooms
      were assigned to choline, trehalose, threonine, leucine/isoleucine, succinic
      acid, alanine, and fumaric acid. The combination of PC 1 (70.8%) and PC 3 (7.5%)
      allowed different grades of cooked pine-mushroom to be discriminated, and the
      major peaks in the (1)H NMR spectra that contributed to discrimination of cooked
      mushrooms were assigned to succinic acid, trehalose, and fumaric acid. This
      metabolomic analysis-based method allows different grades of pine-mushroom to be
      distinguished without any prepurification.

PMID- 17029672
TI  - Analysis of dencichine in Panax notoginseng by gas chromatography-mass
      spectrometry with ethyl chloroformate derivatization.
AB  - Dencichine (beta-N-oxalyl-l-alpha,beta-diaminopropionic acid) is a haemostatic
      agent present in well-known traditional Chinese medicinal herbs such as Panax
      notoginseng, as well as other Panax species. It is also a reported neurotoxic
      agent found in Lathyrus sativus (grass pea seed) and cycad seeds. A method was
      developed for quantitative determination of the non-protein amino acid,
      dencichine, in plant samples of P. notoginseng and the adventitious roots
      directly from the explants of P. notoginseng after derivatization with ethyl
      chloroformate (ECF) by gas chromatography-mass spectrometry (GC-MS). l-2
      chlorophenylalanine was used as an internal standard. Calibration curves were
      linear (r(2)=0.9988, n=6) in the range of 10-800 microg/ml for dencichine. Limit
      of detection and quantification for dencichine were 0.5 microg/ml and 2
      microg/ml, respectively. This rapid and specific method may be applied to the
      quantification of dencichine in complex medicinal plants and their products.

PMID- 17029673
TI  - Sagittal curvature of total knee replacements predicts in vivo kinematics.
AB  - BACKGROUND: It is known that in vivo kinematics after total knee replacement is
      influenced by the design of the implant. The goal of this study was to show that
      the sagittal curvature of two different knee prostheses differing in geometric
      design predicts their in vivo motion behavior. METHODS: Three-dimensional tibio
      femoral displacements of two prosthesis designs (single radius vs. dual radius)
      were measured during knee extension under weight bearing conditions by in vivo
      video fluoroscopy. Finite helical axes were computed to represent the tibio
      femoral motions. Angular deviation alpha and the spatial localization deviation
      delta were used to characterize the motions. Angular deviation is the angle
      between each incremental finite helical axis and the medio-lateral axis of the
      femoral component of the prosthesis. The spatial localization deviation is the
      distance between each finite helical axis and the center of the femoral component
      of the prosthesis. Statistical comparisons were performed using the median and
      the interquartile range of the angular deviation and the spatial localization
      deviation. FINDINGS: The single-radius design showed finite helical axes
      concentrated at a single axis near to the medio-lateral axis of the femoral
      component. The angular and spatial localization deviation of the dual radius
      design were larger compared to the single radius design, exhibiting finite
      helical axes varying between two axes. INTERPRETATION: Video fluoroscopy in
      combination with finite helical axis analysis proved to be suitable methods to
      evaluate the in vivo kinematical behavior of total knee arthroplasty, which can
      be useful for implant designers. Knowledge of in vivo kinematics can also provide
      surgeons with more background information about the total knee arthroplasty
      models they implant.

PMID- 17029674
TI  - Refeeding and insulin activate the AKT/p70S6 kinase pathway without affecting
      IRS1 tyrosine phosphorylation in chicken muscle.
AB  - p70 S6 kinase (p70S6K) is a key enzyme involved in the control of protein
      synthesis. We have previously shown that this kinase is insulin sensitive in
      chicken muscle despite a relative insulin resistance in the early steps of
      insulin receptor signaling in this tissue, particularly with no change in
      tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1). The aim of
      the present study is to further study the p70S6K pathway in chicken muscle. By
      analyzing in silico several kinases involved in the protein kinase B (PKB also
      called AKT)/target of rapamycin (TOR)/p70S6K pathway in the chicken, we showed
      that the amino acid sequence of the proteins exhibited a very high identity with
      their homologs in mammalian species and Drosophila. We investigated the
      regulation of these kinases in vivo or in vitro. Refeeding and insulin treatment
      significantly (P<0.05) increased the phosphorylation and/or activity of kinases
      upstream of p70S6K such as AKT and TOR. Similarly, refeeding and insulin
      increased the phosphorylation of p70S6K on key residues (i.e. T389, T229 and
      T421/S424) and the phosphorylation of a p70S6K downstream target, the ribosomal
      protein S6 (by 3-10-fold, P<0.05). Interestingly, we also showed an increase in
      the phosphorylation level of IRS1 on S632/S635, sites involved in insulin
      resistance. In conclusion, the AKT/TOR/p70S6K pathway is activated by refeeding
      and insulin injection, which might negatively regulate IRS1 tyrosine
      phosphorylation. These results indicate some particularities of the insulin
      signaling in chicken muscle and suggest the involvement of p70S6K in these
      features.

PMID- 17029675
TI  - Modeling growth factor activity during proinflammatory stress: methodological
      considerations in assessing cytokine modulation of IGF binding proteins released
      by cultured bovine kidney epithelial cells.
AB  - The present research was conducted to model potential mechanisms through which
      IGFBPs might be affected by a key proinflammatory response initiating cytokine
      tumor necrosis factor (TNF-)-alpha. Madin-Darby bovine kidney epithelial (MDBK)
      cells, known to release IGFBPs in response to several stimuli, were grown under
      several conditions and challenged with forskolin (F) or recombinant TNF-alpha for
      24h. Forskolin increased IGFBP-3 gene expression and media content of BP-3
      protein. TNF-alpha increased basal and augmented F-mediated IGFBP-3 gene
      expression. However, TNF-alpha effects on the measurable media content of IGFBPs
      were influenced by culture conditions; in the absence of added protease
      inhibitors (PIs) or sufficient media albumin concentration (high BSA, 1mg/ml),
      the effect of TNF-alpha was to decrease (P<0.02) measurable IGFBPs. In the
      presence of PI and high BSA, media IGFBP-3 levels were shown to be increased by
      TNF-alpha consistent with the gene expression data. Changes in media IGFBP-3
      protease activity were examined further to explain the observed effects of TNF
      alpha on production and destruction of IGFBPs in media. When recombinant human
      IGFBP-3 (500 ng/ml) was added to PI-free, low BSA 100 microg/ml) media from TNF
      treated MDBK cells, less than 10% of the BP-3 was recognizable by Western blot in
      30 min; conversely, inclusion of High BSA and PI in media resulted in attenuation
      of the protease effect on the IGFBPs. The data suggest that the MDBK model of
      cellular response to proinflammatory stimulus is affected by culture conditions
      and that TNF-alpha affects media content of IGFBPs through effects on IGFBP gene
      expression coupled with degradation of IGFBPs via enhanced proteolytic enzyme
      release.

PMID- 17029676
TI  - Decreased ACTH secretion during prolonged transportation stress is associated
      with reduced pituitary responsiveness to tropic hormone stimulation in cattle.
AB  - The present study examined the effect of transportation stress on hypothalamic
      pituitary-adrenal axis responsiveness to tropic hormone stimulation and on
      abundance of corticotropin releasing factor (CRF) receptor R1 (CRFR1) and
      arginine vasopressin (AVP) receptor V3 (V3) mRNAs in the anterior pituitary (AP)
      of cattle. Holstein steers were transported for 10 h or used as non-transported
      controls (NTC). Blood samples were collected at start of transportation and every
      1-2h thereafter. To test AP responsiveness to tropic hormones, animals were
      challenged (i.v.) with CRF (0.5 microg/kg), AVP (1 microg/kg) or CRF plus AVP
      immediately after end of transportation and blood samples collected every 30 min
      for 3h. The AP of animals transported for 0, 4 or 10 h were harvested for mRNA
      analyses. Plasma ACTH in transported animals increased within 1h and remained
      elevated for 6 and 8h versus NTC and 0 h values, respectively. Plasma
      concentrations of cortisol increased in response to transportation and remained
      elevated throughout the transport period. Injection of CRF or AVP to NTC animals
      increased plasma ACTH, but ACTH secretion in response to CRF or AVP was
      dramatically reduced in transported animals. ACTH secretion following co
      injection of CRF and AVP tended to be less in transported animals, but was almost
      100% greater than when secretagogues were administered separately. Despite
      decreased AP responsiveness to CRF and AVP, AP CRFR1 and V3 mRNAs were increased
      after 10 h transportation. Results indicate decreased AP responsiveness to CRF
      and AVP may regulate duration of ACTH secretion in response to transportation
      stress in cattle.

PMID- 17029677
TI  - Effect of improved nutrition during calfhood on serum metabolic hormones,
      gonadotropins, and testosterone concentrations, and on testicular development in
      bulls.
AB  - The objective of the present study was to evaluate the effects of improved
      nutrition during calfhood on serum metabolic hormones, gonadotropins and
      testosterone concentrations, and on sexual development in bulls. Bulls received
      high (n=17) or control nutrition (n=16) diets from 10 to 30 week of age and the
      same control nutrition diet from 31 to 74 week of age. Improved nutrition during
      calfhood resulted in a more sustained period of elevated LH secretion (pulse
      frequency and total secretion in 10h) during the early gonadotropin rise. GnRH
      stimulated LH secretion was not affected by diet, indicating that pituitary
      responsiveness was not altered; therefore, improved nutrition had direct effects
      on GnRH secretion by the hypothalamus. Insulin and insulin-like growth factor-I
      (IGF-I) concentrations were greater during calfhood in bulls receiving high
      nutrition, indicating that these metabolic hormones might be involved in
      regulating GnRH and LH secretion. Improved nutrition also resulted in increased
      testosterone secretion that was associated with greater circulating IGF-I
      concentrations, suggesting a role for this metabolic hormone in regulating Leydig
      cell number and function. Furthermore, improved nutrition during calfhood
      resulted in greater testicular weight and sperm production in mature bulls,
      indicating that increased LH secretion during calfhood, and increased IGF-I and
      testosterone concentrations during calfhood and peripubertal period were
      associated with greater testicular cell proliferation and enhanced function.

PMID- 17029678
TI  - [Practice of the thromboembolic disease prophylaxis: a survey among surgeons and
      anaesthetists in Togo].
AB  - OBJECTIVE: The aim of this study was to analyse the current practice of
      postoperative venous thromboembolism (VTE) prophylaxis among anaesthetists, nurse
      anaesthetist and general surgeons in Togo. METHOD: A total of 160 questionnaires
      were distributed to anaesthetists and surgeons with varying subspeciality
      interests. RESULTS: One hundred and three (64%) (3 anaesthetists, 51 nurse
      anaesthetists and 49 surgeons) returned the questionnaire. Of these, 16% thought
      that VTE was as common in Togo as in the western countries. Selective VTE
      prophylaxis was used by 78% of the prescriptors. In order of frequency,
      indications for selective VTE prophylaxis were obesity, increased risk of VTE
      related to surgery and past medical history of VTE. Orthopaedic surgery,
      caesarean section and vascular surgery were most frequently considered as high
      risk surgery for VTE event. When prophylaxis was indicated, low molecular weight
      heparin was prescribed by 87% of prescriptors. In most cases, VTE prophylaxis
      duration was less than a week. In 92% of institutions, there was no written
      protocol for VTE prophylaxis. VTE-related morbidity was reported by 34% of the
      prescriptors over the past year, and 30% of these cases were fatal; 60% of the
      prescriptors observed these complications one week after the surgery. CONCLUSION:
      The practice of VTE prophylaxis in Togo is not sufficient. It is necessary to
      promote the training of practitioners, particularly of physicians.

PMID- 17029679
TI  - [ICU performance: results of a French study involving 80,000 ICU stays].
AB  - OBJECTIVE: The Standard Mortality Ratio (SMR), comparing the observed in-hospital
      mortality to the predicted, may measure the intensive care units (ICU)
      performance. STUDY DESIGN: Multicentric retrospective national study. METHODS: A
      probability model using a severity score such SAPS II calculated the predicted
      mortality rate. A national French study has been undertaken to compare the SMR of
      ICUs and looked for explanation. RESULTS: One hundred six units, 34 were medical
      (32%), 18 surgical (17%) and 57 medical/surgical (51%) participated to the study.
      Forty-six ICUs (43%) were located in teaching hospitals. The SMR of the 87,099
      stays was 0.84 (0.82-0.85). The SMR of ICUs varied from 0.41 to 1.55. Ten units
      had a SMR>0.85, which suggested a low performance. They had more stays for
      cardiovascular failures, as compared with others. The best units (SMR<0.82) had
      more stays for drug overdose. The SMR increased with the number of organ
      failures, from 0.47 with zero failure to 1.11 with 4 or more organ failures. The
      stays with cardiovascular failure, either unique or associated, had a higher SMR.
      The 7935 stays with a drug overdose had a SMR of 0.12 (0.10-0.14), which
      suggested a bad calibration of the model in theses cases. CONCLUSION: The case
      mix must be taken in account when comparing the ICUs performance by the mean of
      SMR, particularly when the units admitted a lot of drug overdoses.

PMID- 17029680
TI  - Accumulation patterns of organochlorines in juveniles of Arctocephalus australis
      found stranded along the coast of Southern Brazil.
AB  - The present study was conducted to elucidate the specific distributions of
      organochlorine (OC) compounds in various tissues and organs of juveniles of the
      South American fur seal (Arctocephalus australis) found stranded on beaches in
      southern Brazil. The OC residue concentrations occurred in the following order:
      PCBs>DDTs>CHLs>HCHs>HCB. OC concentrations in blubber were higher than other
      tissues (e.g. PCBs, 2480 ng g(-1) wet weight; DDTs, 660 ng g(-1) wet weight)
      indicating a positive association with lipid content (except for HCB). However,
      the poor nutritional status of these animals, possibly following a starvation
      period, is likely to have allowed the remobilization of organochlorines stored in
      lipids to other tissues throughout the body, increasing their vulnerability to
      toxic effects and possibly affecting their survival capability.

PMID- 17029681
TI  - Characterization of TSP-bound n-alkanes and polycyclic aromatic hydrocarbons at
      rural and urban sites of Tianjin, China.
AB  - Total suspended particle (TSP) was collected and analyzed at rural and urban
      sites in Tianjin, China during the domestic heating season (from 15 November to
      15 March) of 2003/4 for n-alkanes and 16 polycyclic aromatic hydrocarbons (PAHs).
      The normalized distribution of n-alkanes with the peak at C22, C23, C24 or C25
      suggested that fossil fuel utilization was the major source of particulate n
      alkanes at both sites. PAHs normalized distribution for each sample was similar
      and the higher molecular weight PAH dominated the profile (around 90%) indicating
      a stronger combustion source at both sites. Precipitation and wind were the most
      important meteorological factors influencing TSP and PAHs atmospheric
      concentrations. In the urban area the emission height had significant influence
      on PAHs levels at different heights under the relative stable atmospheric
      conditions. Coal combustion was the major source for TSP-bound PAHs at both sites
      based on some diagnostic ratios.

PMID- 17029682
TI  - Uptake of oxytetracycline and its phytotoxicity to alfalfa (Medicago sativa L.).
AB  - A series of experiments were conducted in a hydroponic system to investigate the
      uptake of oxytetracycline (OTC) and its toxicity to alfalfa (Medicago sativa L.).
      OTC inhibited alfalfa shoot and root growth by up to 61% and 85%, respectively.
      The kinetics of OTC uptake could be well described by Michaelis-Menten equation
      with Vmax of 2.25 micromol g-1 fresh weight h-1, and Km of 0.036 mM. The uptake
      of OTC by alfalfa was strongly inhibited by the metabolic inhibitor, 2,4-DNP (2,4
      dinitrophenol), at pH 3.5 and 6.0, but not by the aquaporin competitors, glycerol
      and Ag+. OTC uptake, however, was significantly inhibited by Hg2+, suggesting
      that the inhibition of influx was due to general cellular stress rather than the
      specific action of Hg2+ on aquaporins. Results from the present study suggested
      that OTC uptake into alfalfa is an energy-dependent process.

PMID- 17029683
TI  - In situ studies on the distribution patterns and dynamics of microcystins in a
      biomanipulation fish--bighead carp (Aristichthys nobilis).
AB  - The distribution and dynamics of microcystins in various organs of the
      phytoplanktivorous bighead carp were studied monthly in Lake Taihu, which is
      dominated by toxic cyanobacteria. There was a good agreement between LC-MS and
      HPLC-UV determinations. Average recoveries of spiked fish samples were 63% for MC
      RR and 71% for MC-LR. The highest MC contents in intestine, liver, kidney and
      spleen were 85.67, 2.83, 1.70 and 1.57 microg g-1 DW, respectively. MCs were much
      higher in mid-gut walls (1.22 microg g-1 DW) than in hind- and fore-gut walls
      (0.31 and 0.18 microg g-1 DW, respectively), suggesting the importance of mid-gut
      wall as major site for MC absorption. A cysteine conjugate of MC-LR was detected
      frequently in kidney. Among the muscle samples analyzed, 25% were above the
      provisional tolerable daily intake level by WHO. Bighead is strongly resistant to
      microcystins and can be used as biomanipulation fish to counteract cyanotoxin
      contamination in eutrophic waters.

PMID- 17029684
TI  - Nutrient losses from manure and fertilizer applications as impacted by time to
      first runoff event.
AB  - Nutrient losses to surface waters following fertilization contribute to
      eutrophication. This study was conducted to compare the impacts of fertilization
      with inorganic fertilizer, swine (Sus scrofa domesticus) manure or poultry
      (Gallus domesticus) litter on runoff water quality, and how the duration between
      application and the first runoff event affects resulting water quality.
      Fertilizers were applied at 35 kg P ha-1, and the duration between application
      and the first runoff event varied between 1 and 29 days. Swine manure was the
      greatest risk to water quality 1 day after fertilization due to elevated
      phosphorus (8.4 mg P L-1) and ammonium (10.3 mg NH4-N L-1) concentrations;
      however, this risk decreased rapidly. Phosphorus concentrations were 2.6 mg L-1
      29 days after fertilization with inorganic fertilizer. This research demonstrates
      that manures might be more environmentally sustainable than inorganic
      fertilizers, provided runoff events do not occur soon after application.

PMID- 17029685
TI  - Simulation of stomatal conductance for Aleppo pine to estimate its ozone uptake.
AB  - The data from a previous experiment carried out in open-top chambers to assess
      the effects of ozone (O3) exposure on growth and physiology of Aleppo pine (Pinus
      halepensis Mill.) were re-assessed to test the performance of the EMEP O3
      stomatal conductance model used to estimate tree O3 uptake at a European scale.
      Aleppo pine seedlings were exposed during three consecutive years to three
      different O3 treatments: charcoal filtered air, non-filtered air and non-filtered
      air supplemented with 40 nl l(-1). The results of the model using the default
      parameterisation already published for Mediterranean conifers showed a poor
      performance when compared to measured data. Therefore, modifications of g(max),
      f(min), and new f(VPD), f(temp) and f(phen) functions were developed according to
      the observed data. This re-parameterisation resulted in a significant improvement
      of the performance of the model when compared to its original version.

PMID- 17029686
TI  - Showing similarity of results given by two methods: a commentary.
AB  - There is a frequent need in the environmental sciences to show the similarity of
      the results given by two analytical methods. This cannot, however, be done within
      the conventional 'there is a difference' statistical hypothesis setting of, among
      others, Student's t-test. We demonstrate here a more appropriate approach that
      originates from drug testing and that can be applied with standard statistical
      software. It is a challenging approach, as it requires quantification of the
      similarity limit. If no pre-determined value is given for similarity, a potential
      data-supported similarity limit can be explored from the data. The approach has
      numerous other potential application areas, e.g. parallelism of regression
      slopes, homogeneity of variances and lack of interaction.

PMID- 17029687
TI  - The ATP-binding cassette transporter ABCA2 as a mediator of intracellular
      trafficking.
AB  - ATP-binding cassette (ABC) transporters are a family of proteins that translocate
      molecules across cellular membranes. Substrates can include lipids, cholesterol
      and drugs. Mutations in ABC transporter genes can cause human pathologies and
      drug resistance phenotypes in cancer cells. ABCA2, the second member the A sub
      family to be identified, was found at high levels in ovarian carcinoma cells
      resistant to the anti-cancer agent, estramustine (EM). In vitro models with
      elevated levels of ABCA2 are resistant to a variety of compounds, including
      estradiol, mitoxantrone and a free radical initiator, 2,2'-azobis-(2
      amidinopropane) (AAPH). ABCA2 is most abundant in the central nervous system
      (CNS), ovary and macrophages. Enhanced expression of ABCA2 and related proteins,
      including ABCA1, ABCA4 and ABCA7, is found in human macrophages upon bolus
      cholesterol treatment. ABCA2 also plays a role in the trafficking of low-density
      lipoprotein (LDL)-derived free cholesterol and is coordinately expressed with
      genes involved in cholesterol homeostasis. Additionally, ABCA2 expression has
      been linked with gene cluster patterns consistent with pathologies including
      Alzheimer's disease (AD). A single-nucleotide polymorphism (SNP) in exon 14 of
      the ABCA2 gene was shown to be linked to early onset AD in humans, supporting the
      observation that ABCA2 expression influences levels of beta-amyloid peptide
      (Abeta), the primary component of senile plaques. ABCA2 may play a role in
      cholesterol transport and affect a cellular phenotype conducive to the
      pathogenesis of a variety of human diseases including AD, atherosclerosis and
      cancer.

PMID- 17029688
TI  - The modified Location Learning Test: norms for the assessment of spatial memory
      function in neuropsychological patients.
AB  - This study examines the applicability of the modified Location Learning Test
      (mLLT) as a test of spatial memory in neuropsychological patients. Three groups
      of participants were examined: stroke patients, patients with diabetes mellitus
      and healthy participants (N=411). Three error measures were computed, the Total
      Score (index of overall performance), the Learning Index (the learning curve over
      subsequent trials) and the Delayed Recall Score, measuring decay over time. The
      Learning Index was the most sensitive measure, showing differences between the
      three groups as well as lateralization effects within the stroke group. Also, the
      mLLT correlated significantly with the Rey Auditory Verbal Learning Test, as well
      as with age and education level. Regression-based normative data were computed
      based on the healthy participants. In all, the mLLT appears to be a sensitive and
      valid test for the detection of object-location memory impairments in clinical
      groups.

PMID- 17029689
TI  - Violent, caring, unpredictable: public views on survivors of brain injury.
AB  - The purpose of the present work was to investigate how members of the public
      perceived survivors of brain injury. A 20-item list of attributes that could be
      used to describe characteristics of survivors of brain injury were given to 323
      participants. One hundred and sixty-nine psychology students and 154 members of
      the public agreed to take part in the study. The effects of group (student and
      public), gender and socioeconomic status (low, moderate and high) on the
      attributes were assessed. Multivariate analysis of variance showed a
      statistically significant difference between the two groups with students holding
      more positive perceptions on 15 out of the 20 attributes. No effects of gender or
      socioeconomic status were found. The research suggests that members of the public
      hold less positive views on survivors of brain injury in respect to intellectual
      competency, ability to care and trustworthiness when compared to students.

PMID- 17029690
TI  - Genome multiplication as adaptation to tissue survival: evidence from gene
      expression in mammalian heart and liver.
AB  - To elucidate the functional significance of genome multiplication in somatic
      tissues, we performed a large-scale analysis of ploidy-associated changes in
      expression of non-tissue-specific (i.e., broadly expressed) genes in the heart
      and liver of human and mouse (6585 homologous genes were analyzed). These species
      have inverse patterns of polyploidization in cardiomyocytes and hepatocytes. The
      between-species comparison of two pairs of homologous tissues with crisscross
      contrast in ploidy levels allows the removal of the effects of species and tissue
      specificity on the profile of gene activity. The different tests performed from
      the standpoint of modular biology revealed a consistent picture of ploidy
      associated alteration in a wide range of functional gene groups. The major
      effects consisted of hypoxia-inducible factor-triggered changes in main cellular
      processes and signaling pathways, activation of defense against DNA lesions,
      acceleration of protein turnover and transcription, and the impairment of
      apoptosis, the immune response, and cytoskeleton maintenance. We also found a
      severe decline in aerobic respiration and stimulation of sugar and fatty acid
      metabolism. These metabolic rearrangements create a special type of metabolism
      that can be considered intermediate between aerobic and anaerobic. The metabolic
      and physiological changes revealed (reflected in the alteration of gene
      expression) help explain the unique ability of polyploid tissues to combine
      proliferation and differentiation, which are separated in diploid tissues. We
      argue that genome multiplication promotes cell survival and tissue regeneration
      under stressful conditions.

PMID- 17029691
TI  - Comparability work and the management of difference in research synthesis
      studies.
AB  - The new imperative to be more methodologically inclusive has generated a
      burgeoning interest in synthesizing the findings of qualitative and quantitative
      studies, or mixed research synthesis. Yet, the very diversity seen to define the
      mixed research synthesis enterprise is also considered to defy it as it
      intensifies the problem of comparing the seemingly incomparable to enable the
      combination of the seemingly uncombinable. We propose here that the research
      synthesis enterprise, in general, and the mixed research synthesis enterprise, in
      particular, entail comparability work whereby reviewers impose similarity and
      difference on the studies to be reviewed. The very study diversity requiring
      management does not exist a priori but rather is itself an outcome of
      comparability work already done whereby judgments have been made about what
      constitutes methodological and topical diversity and uniformity. Conceiving the
      research synthesis process as defined by comparability work moves the backstage
      interpretive work of systematic review to center stage and, thereby, sets a new
      stage for addressing the methodological issues involved. These issues are
      explored by reference to the synthesis of empirical studies of antiretroviral
      adherence in HIV-positive women in the US.

PMID- 17029693
TI  - Intellectual property organizations and pharmaceutical patents in Africa.
AB  - This article builds on a previous study which found low numbers of patent
      applications for HIV antiretroviral drugs in African countries. A high level of
      variation was noted across individual countries, and consequently, the present
      study has sought to account for sources of the variation through statistical
      analyses. First, a correlation between the number of patents and HIV infection
      rate was observed (r=0.448, p<0.001). T-tests identified significantly higher
      numbers of patents in national members of two intellectual property organizations
      (IPOs)-African Regional Intellectual Property Orginisation (ARIPO) and the
      Organisation Africaine de la Propriete Intellectualle (OAPI)-than in countries
      who did not belong to an intellectual property organization. The relationship
      between IPO membership and number of patents was also statistically significant
      in a multivariate Poisson regression. These findings demonstrate that higher
      numbers of patents are found in countries where they are more easily filed. This
      has important policy implications given the worldwide trend toward increased
      recognition of pharmaceutical patents.

PMID- 17029692
TI  - Does social capital enhance health and well-being? Evidence from rural China.
AB  - Despite increasing acknowledgement that social capital is an important
      determinant of health and overall well-being, empirical evidence regarding the
      direction and strength of these linkages in the developing world is limited and
      inconclusive. This paper empirically examines relationships between social
      capital and health and well-being-as well as the suitability of commonly used
      social capital measures-in rural China, where rapid economic growth coexists with
      gradual and fundamental social changes. To measure social capital, we adopt a
      structural/cognitive distinction, whereby structural social capital is measured
      by organizational membership and cognitive social capital is measured by a
      composite index of trust, reciprocity, and mutual help. Our outcome measures
      included self-reported general health, psychological health, and subjective well
      being. We adopt multi-level estimation methods to account for our
      conceptualization of social capital as both an individual- and contextual-level
      resource. Results indicate that cognitive social capital (i.e., trust) is
      positively associated with all three outcome measures at the individual level and
      psychological health/subjective well-being at the village level as well. We
      further find that trust affects health and well-being through pathways of social
      network and support. In contrast, there is little statistical association or
      consistent pattern between structural social capital (organizational membership)
      and the outcome variables. Furthermore, although organizational membership is
      highly correlated with collective action, neither is associated with health or
      well-being. Our results suggest that policies aimed at producing an environment
      that enhances social networks and facilitates the exchange of social support hold
      promise for improving the health and well-being of the rural Chinese population.
      In addition, China may not have fully taken advantage of the potential
      contribution of structural social capital in advancing health and well-being. A
      redirection of collective action from economic to social activities may be worth
      considering.

PMID- 17029694
TI  - Tautomerism, acid-base properties and conformation of methylated analogues of the
      promutagenic N4-hydroxycytosine.
AB  - UV and NMR spectroscopy were employed to study the tautomerism, acid-base
      properties and conformation of the exocyclic N(4)-OH group in 1-methyl-N(4)
      hydroxycytosine (1-mOH(4)C), and its methyl derivatives, viz. the fixed imino
      forms (1,3-m(2)OH(4)C and 1,3,5-m(3)OH(4)C), the fixed amino form (1,N(4)
      m(2)OH(4)C), and analogues sterically constrained to the form syn (1,5
      m(2)OH(4)C) or anti (1,3-m(2)OH(4)C) with respect to the ring N(3). Relative to
      1,N(4)-m(2)OH(4)C, UV spectroscopy showed that the other analogues were
      predominantly imino and that all analogues formed a structurally common cation in
      acid medium, with results pointing to approximately 90% population of the imino
      species for 1-mOH(4)C and 1,5-m(2)OH(4)C, further supported by NMR spectroscopy.
      Both exhibited two sequential dissociations in alkaline medium, the first due to
      N(4)-OH, followed by the N(3)-H. (1)H and (13)C NMR spectroscopy showed 1-mOH(4)C
      in the conformation syn. With 1,3,5-m(3)OH(4)C, an ;overcrowded' planar molecule
      with steric constraints to both the syn and anti conformations, a syn-anti
      equilibrium is observed, with a preference of approximately 75% for the anti
      rotamer, independently of the polarity of the medium. Exchange between the
      rotamers is slow on the NMR time-scale, with a minimal barrier to exchange
      exceeding 100 kJ/mol. In low-polar media, the analogues associate as dimers via
      O(4)-Hcdots, three dots, centeredO(2) or O(4)-Hcdots, three dots, centeredN(4)
      hydrogen bonds, with association constants at ambient temperature of 4.6 (1,3
      m(2)OH(4)C), 12.8 (anti 1,3,5-m(3)OH(4)C), 36 (1,5-m(2)OH(4)C), 109 (syn 1,3,5
      m(3)OH(4)C) M(-1). Implications of the overall findings to the promutagenic
      activities of OH(4)C and OMe(4)C are examined.

PMID- 17029695
TI  - Electrophoresis of long DNA molecules in linear polyacrylamide solutions.
AB  - Electrophoresis of long DNA (T4 DNA; 166 kb, S. pombe chromosomal DNA; 3-6 Mb) in
      linear polyacrylamide solutions was investigated by fluorescence microscopy and
      capillary electrophoresis. In the past studies on electrophoresis of long DNA in
      a polymer solution, it was reported that DNA migrates in 'U-shape conformation'.
      We found that at higher polymer concentrations, the shape of the migrating DNA
      changes from U shape to linear shape ('I-shape conformation'). In the migration
      mode with the I-shape conformation, the DNA moves with almost constant velocity
      and constant shape. However, the migration velocity does depend on the DNA size,
      and it is possible to separate DNAs under this I-shape motion. Actually, Mb-sized
      DNAs are well separated within 5 min in the region for the I-shape motion by
      means of capillary electrophoresis with a DC field. Considering that it takes 20
      h to separate Mb-sized DNAs by standard pulsed-field gel electrophoresis (PFGE),
      this results will be useful for the separation of giant DNAs.

PMID- 17029696
TI  - Mitochondria as an important factor in the maintenance of constant amplitudes of
      cytosolic calcium oscillations.
AB  - Theoretical models of intracellular calcium oscillations have hitherto focused on
      the endoplasmic reticulum (ER) as an internal calcium store. These models
      reproduced the large variability in oscillation frequency observed
      experimentally. In the present contribution, we extend our earlier model [Marhl
      et al., Biophys. Chem., 63 (1997) 221] by including, in addition to the ER,
      mitochondria as calcium stores. Simple plausible rate laws are used for the
      calcium uptake into, and release from, the mitochondria. It is demonstrated with
      the help of this extended model that mitochondria are likely to act in favour of
      frequency encoding by enabling the maintenance of fairly constant amplitudes over
      wide ranges of frequency.

PMID- 17029697
TI  - Monte Carlo studies on potentiometric titration of poly(glutamic acid).
AB  - The potentiometric titration of poly(glutamic acid) with special attention to its
      helix-coil transition is investigated in terms of the previously developed Monte
      Carlo method. The simulations of the potentiometric titration are carried out for
      helical and coiled form of the peptide, separately. A cylindrical rod with
      spherical ionizable groups is adopted as each conformational model of
      poly(glutamic acid) molecule. A spherical charge with a hard core potential is
      assumed as a mobile hydrated ion. The helix-coil transition curves are analyzed
      by the Zimm-Bragg theory. A satisfactory agreement is achieved for the titration
      curves with the experimental data in most cases. The significance and the
      limitations of the simulation method are discussed.

PMID- 17029698
TI  - On the need to consider kinetic as well as thermodynamic consequences of the
      parking problem in quantitative studies of nonspecific binding between proteins
      and linear polymer chains.
AB  - Attention is drawn to a need for caution in the thermodynamic characterization of
      nonspecific binding of a large ligand to a linear acceptor such as a
      polynucleotide or a polysaccharide-because of the potential for misidentification
      of a transient (pseudoequilibrium) state as true equilibrium. The time course of
      equilibrium attainment during the binding of a large ligand to nonspecific three
      residue sequences of a linear acceptor lattice has been simulated, either by
      numerical integration of the system of ordinary differential equations or by a
      Monte Carlo procedure, to identify the circumstances under which the kinetics of
      elimination of suboptimal ligand attachment (called the parking problem) create
      such difficulties. These simulations have demonstrated that the potential for the
      existence of a transient plateau in the time course of equilibrium attainment
      increases greatly (i) with increasing extent of acceptor saturation (i.e., with
      increasing ligand concentration), (ii) with increasing magnitude of the binding
      constant, and (iii) with increasing length of the acceptor lattice. Because the
      capacity of the polymer lattice for ligand is most readily determined under
      conditions conducive to essentially stoichiometric interaction, the parameter so
      obtained is thus likely to reflect the transient (irreversible) rather than
      equilibrium binding capacity. A procedure is described for evaluating the
      equilibrium capacity from that irreversible parameter; and illustrated by
      application to published results [M. Nesheim, M.N. Blackburn, C.M. Lawler, K.G.
      Mann, J. Biol. Chem. 261 (1986) 3214-3221] for the stoichiometric titration of
      heparin with thrombin.

PMID- 17029699
TI  - Actinic light and pH effect on the proton pumping of bacteriorhodopsin.
AB  - The actinic light effect on the bacteriorhodopsin (BR) photocycle kinetics led to
      the assumption of a cooperative interaction between the photocycling BR
      molecules. In this paper we report the results of the actinic light effect and pH
      on the proton release and uptake kinetics. An electrical method is applied to
      detect proton release and uptake during the photocycle [E. Papp, G. Fricsovszky,
      J. Photochem. Photobiol. B: Biol. 5 (1990) 321]. The BR photocycle kinetics was
      also studied by absorption kinetics measurements at 410 nm and the data were
      analyzed by the local analysis of the M state kinetics [E. Papp, V.H. Ha,
      Biophys. Chem. 57 (1996) 155]. While at high pH and ionic strength, we found a
      similar behavior as reported earlier, at low ionic strength the light effect
      proved to be more complex. The main conclusions are the following: Though the
      number of BR excited to the photocycle (fraction cycling, fc) goes to saturation
      with increasing laser pulse energy, the absorbed energy by BR increases linearly
      with pulse energy. From the local analysis we conclude that the light effect
      changes the kinetics much earlier, already at the L intermediate state decay. The
      transient electric signal, caused by proton release and uptake, can be decomposed
      into two components similarly to the absorption kinetic data of the M
      intermediate state. The actinic light energy affects mainly the ratio of the two
      components and the proton movements inside BR while pH has an effect on the
      kinetics of the proton release and uptake groups at the membrane surface.

PMID- 17029700
TI  - Receptor regulation in neuroendocrine-immune communication: current knowledge and
      future perspectives.
AB  - Immune cells express receptors for every hormone or neurotransmitter we know so
      far. The neuroendocrine system signals to the immune system via the release of
      hormones and neurotransmitters that regulate cellular activity via these
      receptors. Much attention has been focused on the effect of glucocorticoids and
      catecholamines on the immune system. Glucocorticoids communicate with immune
      cells via glucocorticoid receptors of which the activity itself changes during
      immune activation. Many neuroendocrine mediators are ligands for G-protein
      coupled receptors on immune cells. Cytokines, oxygen-radicals, and catecholamines
      can influence the responsiveness of G-protein coupled receptors via decreasing
      the intracellular level of so-called G-protein coupled receptor kinases, of which
      the subtype GRK2 is highly expressed in immune cells. Therefore, changes in only
      one kinase can modulate the sensitivity of many receptors. We describe here that
      sensitivity of neuroendocrine receptors on immune cells is constantly regulated
      by inflammatory processes or chronic stress, which implies that not only the
      activity of the neuroendocrine system determines communication but that the
      sensitivity of receptors is a major factor in determining the final immune
      response. Finally, consequences of alterations in GRK2 during (neuro)
      inflammatory diseases are discussed.

PMID- 17029701
TI  - Maternal antibrain antibodies in autism.
AB  - Autism is a neurodevelopmental disorder of prenatal onset that is behaviorally
      defined. There is increasing evidence for systemic and neuroimmune mechanisms in
      children with autism. Although genetic factors are important, atypical prenatal
      maternal immune responses may also be linked to the pathogenesis of autism. We
      tested serum reactivity in 11 mothers and their autistic children, maternal
      controls, and several groups of control children, to prenatal, postnatal, and
      adult rat brain proteins, by immunoblotting. Similar patterns of reactivity to
      prenatal (gestational day 18), but not postnatal (day 8) or adult rat brain
      proteins were identified in autistic children, their mothers, and children with
      other neurodevelopmental disorders, and differed from mothers of normal children,
      normal siblings of children with autism and normal child controls. Specific
      patterns of antibody reactivity were present in sera from the autism mothers,
      from 2 to 18 years after the birth of their affected children and were unrelated
      to birth order. Immunoblotting using specific antigens for myelin basic protein
      (MBP) and glial acidic fibrillary protein (GFAP) suggests that these proteins
      were not targets of the maternal antibodies. The identification of specific serum
      antibodies in mothers of children with autism that recognize prenatally expressed
      brain antigens suggests that these autoantibodies could cross the placenta and
      alter fetal brain development.

PMID- 17029702
TI  - Poor sleep the night before an experimental stressor predicts reduced NK cell
      mobilization and slowed recovery in healthy women.
AB  - Sleep is important for health; however, poor sleep is a growing problem in many
      Western societies, particularly among women. Alterations in immune function
      following poor sleep (defined by duration and disruption) may be linked to ill
      health. Not yet investigated are the possible effects on stress-induced
      mobilization of lymphocytes. As natural killer (NK) cells are particularly
      responsive to acute stress, the present study examined whether sleep period
      duration and percentage of time awake after sleep onset (WASO) the night before a
      laboratory stressor would predict reduced NK cell mobilization. Sleep was
      monitored by actigraphy in 39 healthy women. NK cell peripheral blood numbers
      were determined at baseline (post-20 min rest), 4 min into a Stroop task,
      immediately post-task and 30 min after task completion. Participants with high
      WASO had significantly less NK cell mobilization to the stressor and failed to
      return to baseline levels after 30 min compared to women with low WASO. No
      effects were found for sleep period duration. Findings raise the possibility that
      inadequate NK cell mobilization to, and poor recovery from acute stress may be
      one pathway by which sleep could impact health.

PMID- 17029703
TI  - Psychosocial stress increases inflammatory markers and alters cytokine production
      across pregnancy.
AB  - Previous work has shown that psychosocial stress is related to increases in serum
      levels of pro-inflammatory cytokines late in pregnancy, and a growing body of
      research suggests that increased inflammatory activity during pregnancy,
      generally, may have a negative impact on outcome. The present study further
      addressed these issues by assessing relationships between psychosocial stress,
      social support and serum cytokines in early, mid, and late pregnancy, and the
      effects of stress and social support on the production of cytokines by stimulated
      lymphocytes in late pregnancy. In addition, we examined relationships between
      stress, support, and serum C-reactive protein (CRP) during pregnancy. Elevated
      stress was not only related to higher serum IL-6 late in pregnancy as in our
      prior work, but this relationship was also evident during early pregnancy and
      elevated stress was also associated with lower IL-10 in early pregnancy. No
      relationships between stress and cytokines were apparent during the 2nd trimester
      of pregnancy. Elevated stress during the 2nd trimesters and low social support
      during the 3rd trimester were related to increased serum levels of CRP, further
      suggesting that psychosocial factors can contribute increased inflammation during
      pregnancy. Importantly, elevated stress levels across pregnancy were predictive
      of elevated production of the pro-inflammatory cytokines IL-1B and IL-6 by
      stimulated lymphocytes in the 3rd trimester, suggesting that stress during
      pregnancy affects the function of immune system cells. These findings further
      support the notion that prenatal stress alters maternal physiology and immune
      function in a manner consistent with increased risk of pregnancy complications
      such as preeclampsia and premature labor.

PMID- 17029704
TI  - Sustained oscillations in glycolysis: an experimental and theoretical study of
      chaotic and complex periodic behavior and of quenching of simple oscillations.
AB  - We report sustained oscillations in glycolysis conducted in an open system (a
      continuous-flow, stirred tank reactor; CSTR) with inflow of yeast extract as well
      as glucose. Depending on the operating conditions, we observe simple or complex
      periodic oscillations or chaos. We report the response of the system to
      instantaneous additions of small amounts of several substrates as functions of
      the amount added and the phase of the addition. We simulate oscillations and
      perturbations by a kinetic model based on the mechanism of glycolysis in a CSTR.
      We find that the response to particular perturbations forms an efficient tool for
      elucidating the mechanism of biochemical oscillations.

PMID- 17029705
TI  - Oscillations in peroxidase-catalyzed reactions and their potential function in
      vivo.
AB  - The peroxidase-oxidase reaction has become a model system for the study of
      oscillations and complex dynamics in biochemical systems. In the present paper we
      give an overview of previous experimental and theoretical studies of the
      peroxidase-oxidase reaction. Recent in vitro experiments have raised the question
      whether the reaction also exhibits oscillations and complex dynamics in vivo. To
      investigate this possibility further we have undertaken new experimental studies
      of the reaction, using horseradish extracts and phenols which are widely
      distributed in plants. The results are discussed in light of the occurrence and a
      possible functional role of oscillations and complex dynamics of the peroxidase
      oxidase reaction in vivo.

PMID- 17029706
TI  - Calcium waves and oscillations in eggs.
AB  - Eggs from several protostomes (molluscs, annelids, nemerteans, etc.) and two
      deuterostomes (mammals and ascidians) display repetitive calcium signals.
      Oscillations in the level of intracellular calcium concentration are occasionally
      triggered by maturing hormones (as in some molluscs) and mostly observed after
      fertilization which occurs at different stages of the meiotic cell cycle (oocytes
      are arrested in prophase, metaphase I or metaphase II). In most eggs examined so
      far, calcium oscillations last until the end of meiosis just before male and
      female pronuclei form. This ability depends on the sensitivity of InsP3 channels
      and on the permeability of the plasma membrane to extracellular calcium. In eggs
      that undergo cytoplasmic reorganization at fertilization (annelids, nemerteans,
      ascidians, etc.) the repetitive calcium signals are waves that originate from
      localized cortical sites that become calcium waves pacemakers. In ascidians we
      have identified the site of initiation of repetitive calcium waves as an
      accumulation of endoplasmic reticulum sandwiched between the plasma membrane and
      an accumulation of mitochondria. We compare and discuss the generation of calcium
      signals in the different eggs, their relationship with the cell cycle and the
      possible roles they play during development.

PMID- 17029707
TI  - From bistability to oscillations in a model for the isocitrate dehydrogenase
      reaction.
AB  - Considered is a bienzymatic system consisting of isocitrate dehydrogenase (IDH,
      EC 1.1.1.42), which transforms NADP(+) into NADPH, and of diaphorase (DIA, EC
      1.8.1.4), which catalyzes the reverse reaction. Experimental evidence as well as
      a theoretical model show the possibility of a coexistence between two stable
      steady states in this reaction system. The phenomenon originates from the
      regulatory properties of IDH. We extend the analysis of a theoretical model
      proposed for the IDH-DIA bienzymatic system and investigate the occurrence of
      different modes of bistability, with or without hysteresis, i.e. in the presence
      of two or only one limit point bounding the domain of multiple steady states. The
      analysis indicates that the two types of bistability may sometimes be observed
      sequentially as a given control parameter is progressively increased. We further
      obtain conditions in which sustained oscillations develop in the model. These
      results establish the isocitrate dehydrogenase reaction coupled to diaphorase as
      a suitable candidate for further experimental and theoretical studies of
      bistability and oscillations in biochemical systems.

PMID- 17029708
TI  - Bistability and the species barrier in prion diseases: stepping across the
      threshold or not.
AB  - The infectious agent of transmissible spongiform encephalopathies is thought to
      be a cellular protein, the prion protein, which undergoes, under some
      circumstances, a dramatic conformational change leading to pathogenesis. The
      conversion between the normal and pathogenic isoforms corresponds to a
      autocatalytic mechanism and the metabolism of the prion protein exhibits switches
      between a normal, stable steady state and a pathogenic one. When the disease can
      be transmitted between two species, a primary infection from a heterologous donor
      has to be followed by two passages in the same host species so that the
      incubation period is stabilized. Sometimes, no pathogenic isoform of the prion
      protein is detected after the first passage, although corresponding brain
      extracts remain infectious. The observation that three and only three passages
      are needed in order to stabilize the strain strongly suggests that, during the
      course of the primary infection by the heterologous donor, an intermediary
      conformational species is formed. Within this assumption, a common mechanism
      involving only conformational changes of the prion protein can give a unifying
      interpretation of the problem of species barrier, lag characteristics and
      apparent lack of detection of the pathogenic isoform after the first passage in
      experiments dealing with interspecies transmission of prion diseases.

PMID- 17029709
TI  - Molecular characterisation of Salmonella strains by an oligonucleotide multiprobe
      microarray.
AB  - A DNA microarray has been developed for the simultaneous characterisation and
      typing of Salmonella enterica subsp. enterica isolates. One-hundred and nine 35
      40 mer oligonucleotides probes detect flagellar and somatic antigen encoding
      genes (serogroup or serotype specific), important virulence genes located within
      or outside the pathogenicity islands, phage-associated genes and antibiotic
      resistance determinants. The probes were printed on glass slides and whole
      genomic Cy5-labelled Salmonella DNA was hybridised to the substrate. A set of 19
      different Salmonella strains and one Escherichia coli strain has been selected as
      positive and negative controls for each probe. The validity of the results is
      confirmed by gene-specific PCRs or phenotypic methods (serotyping, MIC
      determination for various antimicrobial agents). Of 2071 data points generated,
      an agreement of 97.4% has been obtained between microarray and PCR/phenotypic
      results. Twenty-six data points (1.3%) were classified as uncertain and,
      similarly, 1.3% showed a discordant result. The microarray described here is a
      new tool to study the epidemiology of Salmonella strains on the genotypic level
      and might become a powerful method in risk assessment studies.

PMID- 17029710
TI  - Neuropsychological sequelae from acute poisoning and long-term exposure to
      carbamate and organophosphate pesticides.
AB  - This research examines the effects of different degrees of pesticide exposure on
      neuropsychological performance. Exposures varied from acute poisoning coupled
      with chronic exposure to low or high levels of chronic exposure (defined by years
      of exposure). A cross-sectional neuropsychological and biochemical study was
      conducted in greenhouse farmers from southern Spain: data from 24 acutely
      poisoned workers and 40 non-poisoned but chronically (low or high) exposed
      sprayers were compared to 26 controls. We examined performance on 21
      neuropsychological tests that assessed attention, memory, praxis, gnosis, motor
      coordination, naming and reasoning and also examined values of plasmatic
      cholinesterase. Results indicated statistically significant neuropsychological
      deficits in the acute poisoning and high chronic exposure groups after
      controlling for confounds, whereas similar performance was seen in the low
      chronic exposed subjects and controls. Subjects who were acutely poisoned
      performed worse than the other groups on perceptual, visuomotor, visual memory
      and mood state domains. Both the acutely poisoned and the chronically high
      exposed subjects obtained significantly lower scores in the perceptual, verbal
      memory and visuomotor domains. Levels of butyrylcholinesterase were related to
      the seasonal sprayer activity except in the case of acutely poisoned subjects.
      CONCLUSIONS: Both acutely poisoned long-term workers and chronically high (>10
      years) exposed workers exhibited similar disturbances in perception and visuo
      motor processing, in the absence of any related acute effect of
      butyrylcholinesterase inhibition. In the case of acutely poisoned subjects,
      verbal and perceptive learning and recall and constructive abilities were also
      impaired. These results point to the need for follow-up studies to assess the
      possible sequelae of chronic and acute exposure to pesticides and their
      interactions.

PMID- 17029711
TI  - Anaerobic stopped-flow studies of indole-3-acetic acid oxidation by dioxygen
      catalysed by horseradish C and anionic tobacco peroxidase at neutral pH: catalase
      effect.
AB  - The effect of order of reagent mixing in the absence and in the presence of
      catalase on the transient kinetics of indole-3-acetic acid (IAA) oxidation by
      dioxygen catalysed by horseradish peroxidase C and anionic tobacco peroxidase at
      neutral pH has been studied. The data suggest that haem-containing plant
      peroxidases are able to catalyse the reaction in the absence of exogenous
      hydroperoxide. The initiation proceeds via the formation of the ternary complex
      enzyme-->IAA-->oxygen responsible for IAA primary radical generation. The
      horseradish peroxidase-catalysed reaction is independent of catalase indicating a
      significant contribution of free radical processes into the overall mechanism.
      This is in contrast to the tobacco peroxidase-catalysed reaction where the
      peroxidase cycle plays an important role. The transient kinetics of IAA oxidation
      catalysed by tobacco peroxidase exhibits a biphasic character with the first
      phase affected by catalase. The first phase is therefore associated with the
      common peroxidase cycle while the second is ascribed to native enzyme interaction
      with skatole peroxy radicals yielding directly Compound II.

PMID- 17029712
TI  - Computer simulation of damped oscillations during peroxidase-catalyzed oxidation
      of indole-3-acetic acid.
AB  - Oscillation patterns in horseradish peroxidase (HRP)-catalyzed oxidation of
      indole-3-acetic acid (IAA) at neutral pH were studied using computer simulation.
      Under certain conditions, such as the presence of a reaction promoter and
      continuous intake of oxygen from the gaseous phase, the simulated system exhibits
      damped oscillations of the concentrations of oxygen in the aqueous phase,
      [O(2)](aq), and of all the reaction intermediates. The critical concentration of
      oxygen in aqueous phase, [O(2)](cr)(aq), was used to describe the nature of the
      oscillations. The critical concentration is the concentration at which the system
      abruptly changes its properties. If [O(2)](aq) is higher than [O(2)](cr)(aq) then
      the reaction develops as an avalanche, otherwise, the reaction stops. The nature
      of oscillations is accounted for by the interaction of two processes: the
      consumption/accumulation of oxygen and the accumulation/consumption of reaction
      intermediates. Oscillations are always damped. Neither HRP or umbelliferone (Umb)
      deactivation nor IAA consumption can account for the damping. The nature of the
      damping is determined by the termination reactions of free radical intermediates
      and ROOH. The three major parameters of oscillations: period of oscillations,
      initial amplitude of oscillations and the rate of damping were studied as
      functions of: (i) oxygen concentration in the gaseous phase, (ii) initial oxygen
      concentration in aqueous phase, (iii) the concentration of IAA and (iv) the
      initial concentration of HRP.

PMID- 17029713
TI  - Neural network explanation using inversion.
AB  - An important drawback of many artificial neural networks (ANN) is their lack of
      explanation capability [Andrews, R., Diederich, J., & Tickle, A. B. (1996). A
      survey and critique of techniques for extracting rules from trained artificial
      neural networks. Knowledge-Based Systems, 8, 373-389]. This paper starts with a
      survey of algorithms which attempt to explain the ANN output. We then present
      HYPINV, a new explanation algorithm which relies on network inversion; i.e.
      calculating the ANN input which produces a desired output. HYPINV is a
      pedagogical algorithm, that extracts rules, in the form of hyperplanes. It is
      able to generate rules with arbitrarily desired fidelity, maintaining a fidelity
      complexity tradeoff. To our knowledge, HYPINV is the only pedagogical rule
      extraction method, which extracts hyperplane rules from continuous or binary
      attribute neural networks. Different network inversion techniques, involving
      gradient descent as well as an evolutionary algorithm, are presented. An
      information theoretic treatment of rule extraction is presented. HYPINV is
      applied to example synthetic problems, to a real aerospace problem, and compared
      with similar algorithms using benchmark problems.

PMID- 17029714
TI  - Contributions of dipole moments, quadrupole moments, and molecular
      polarizabilities to the anesthetic potency of fluorobenzenes.
AB  - Previous studies have emphasized the role of molecular polarizability and
      electric moments, especially dipole and quadrupole moments, in binding of drugs
      to sites of action. A recent publication of ED50s that prevent response to a
      noxious stimulus for eight fluorobenzenes has made it possible to compare
      anesthetic potency with ab initio Hartree-Fock calculations of molecular
      polarizability as well as dipole and quadrupole moments. Fluorobenzenes provide a
      stringent test of the role of electric moments in anesthetic potency because
      individual dipole moments range from 0 to 2.84 debye (D) while the quadrupole
      moment of benzene is large and negative (-30 x 10(-40) C m(2)), that of
      hexafluorobenzene is large and positive (30 x 10(-40) C m(2)), and that of 1,3,5
      trifluorobenzene is nearly zero. We found that anesthetic potency of
      fluorobenzenes was not affected by the presence of either dipole or quadrupole
      moments. This result is surprising because fluoroalkanes and fluorocycloalkanes
      are most potent when half fluorinated and are usually not anesthetics when
      perfluorinated. The results suggest that electrostatic interactions are not
      important for binding of fluorobenzenes at sites of anesthetic action and that
      these sites are different from those that bind conventional anesthetics.

PMID- 17029715
TI  - An experimental methodology for measuring volume changes in proton transfer
      reactions in aqueous solutions.
AB  - A fast perturbation in proton concentration can be induced in aqueous solution
      using a pulsed ultraviolet laser and suitable photolabile compounds which, upon
      photoexcitation, irreversibly release protons. The volume change and the rate
      constant for the reaction of the photodetached protons with proton-accepting
      groups in solution can be monitored using time resolved photoacoustics. A typical
      proton concentration jump of 1 microM can be obtained with a 200-microJ laser
      pulse at 308 nm. Reaction dynamics from 20 ns to 5 micros can be easily followed.
      The methodology we establish represents a direct, time-resolved measurement of
      the reaction volume in proton transfer processes and an extension to the
      nanosecond-microsecond range of traditional relaxation techniques, such as
      stopped-flow. We report example applications to reactions involving simple
      molecules and polypeptides.

PMID- 17029716
TI  - Effect of the cation and the anion of an electrolyte on the solubility of DL
      aminobutyric acid in aqueous solutions: measurement and modelling.
AB  - The solubilities at 298.2 K of dl-aminobutyric acid in aqueous solutions of NaCl,
      KCl, NaNO(3) and KNO(3) were measured. The solubility of DL-aminobutyric acid was
      found to be influenced by the concentration and by the nature of both the cation
      and the anion of the electrolyte. Comparison of the results obtained in this
      study and those for other amino acids reported in the literature, indicates that
      the structure of the hydrocarbon backbone of an amino acid plays an important
      role in the interactions of an amino acid with an electrolyte. A thermodynamic
      model has been used to correlate the solubilities of DL-aminobutyric acid in
      aqueous electrolyte solutions. The activity coefficients of the amino acid in the
      electrolyte solutions, were represented by a model proposed by Khoshkbarchi and
      Vera [M.K. Khoshkbarchi, J.H. Vera, AIChE J. 42 (1996) 2354; M.K. Khoshkbarchi,
      J.H. Vera, Ind. Eng. Chem. Res. 35 (1996) 4755]. This model, which considers a
      combination of both long- and short-range interactions, contains only two
      adjustable parameters. All other parameters are available in the literature. The
      model can accurately correlate the solubility of dl-aminobutyric acid in aqueous
      solutions of electrolytes.

PMID- 17029717
TI  - Dynamic model of hormonal systems coupled by negative feedback.
AB  - Most hormone concentrations in the body are regulated by negative feedback
      mechanisms in which the production and release of hormones are regulated
      according to the concentration of related species. Also, it has been observed
      that several hormones are released in a variety of pulsatile patterns. In most
      cases, the mechanism driving these complex patterns is not well understood. Our
      model of two cells coupled through negative feedback to their external products
      demonstrates periodic, aperiodic and chaotic oscillations. The coupling between
      the cells seems to be responsible for these dynamic behaviors. The variety of
      dynamic behaviors observed in the model demonstrates that a simple physiological
      feedback loop mimicking the coupling between circulatory hormones and production
      centers could be the source of complex hormone release patterns observed in vivo.

PMID- 17029718
TI  - Rigid-body oscillations of alpha-helices: implications for protein thermal
      stability.
AB  - A quasi-continuity model protein consisting of two alpha-helices undergoing rigid
      body torsional oscillations demonstrates that factors stabilizing the model
      protein, such as increased helix rigidity and hydrophobicity, are the same
      factors that stabilize thermophilic proteins relative to their mesophilic
      analogs. The model predicts oscillatory motions with frequencies in the microwave
      (10(10) Hz) range. These oscillations decrease in frequency with increasing helix
      rigidity because of compensating increases in the force constant and moment of
      inertia, thus explaining the retention of activity in the more rigid thermophilic
      enzymes. Implications for protein design, based on the predictions of the model,
      are discussed.

PMID- 17029719
TI  - (17)O NMR of water in ordered environments.
AB  - Two NMR experiments are designed for selective excitation of spin I=5/2 nuclei
      that exhibit residual quadrupolar splittings. The I=5/2 Jeener-Broekaert
      experiment is preferred to the four-quantum filtration experiment as it is shown
      to be a more sensitive technique in experimental practice. Both techniques are
      applied to (17)O-enriched water in biological systems. The occurrence of water
      which displays a residual (17)O quadrupolar splitting is demonstrated for the
      first time in a model biological system and an excised tissue sample. The
      resulting (17)O NMR spectra are shown to have the characteristics predicted in
      computer-simulated I=5/2 NMR spectra.

PMID- 17029720
TI  - Azide accelerates the decay of M-intermediate of pharaonis phoborhodopsin.
AB  - Natronobacterium pharaonis has retinal proteins, one of which is pharaonis
      phoborhodopsin, abbreviated as ppR (or called pharaonis sensory rhodopsin II, psR
      II). This pigment protein functions as a photoreceptor of the negative phototaxis
      of this bacterium. On photoexcitation ppR undergoes photocycling; the
      photoexcited state relaxes in the dark and returns to the original state via
      several intermediates. The photocycle of ppR resembles that of bR except in
      wavelengths and rate. The cycle of bR is completed in 10 ms while that of ppR
      takes seconds. The Arrhenius analysis of M-intermediate (ppR(M)) decay which is
      rate-limiting revealed that the slow decay is due to the large negative
      activation entropy of ppR. The addition of azide increases the decay rate 300
      fold (at pH 7); Arrhenius analysis revealed decreases in the activation energy
      (activation enthalpy) and a further decrease in the activation entropy.

PMID- 17029721
TI  - The partial molar heat capacity and volume of the peptide backbone group of
      proteins in aqueous solution.
AB  - The partial molar heat capacities have been determined for the series of peptides
      alanyl(glycyl)(x)glycine, x=1-3, and for the compounds N-acetylglycinamide and N
      acetyl glycylglycinamide in aqueous solution over the temperature range 10-100
      degrees C using high sensitivity scanning microcalorimetry. The partial molar
      volumes for these compounds have also been determined over the temperature range
      from 10 to 90 degrees C using a scanning densimetric method. The results were
      used to derive the partial molar heat capacities and volumes of the glycyl group
      at temperatures in the range 10-100 degrees C. The results obtained are
      critically compared with literature results derived using heat capacity and
      volume data for some oligoglycines.

PMID- 17029722
TI  - The Synthesizing Unit as model for the stoichiometric fusion and branching of
      metabolic fluxes.
AB  - The Synthesizing Unit (SU) binds given numbers of substrate molecules of several
      types of substrate to produce a product molecule or set of product molecules.
      Irreversible binding results in relatively simple and explicit expressions for
      the rate of product formation. Reversible binding can be implemented with
      relative ease in the carrier-SU complex, where the products of a set of carriers
      (a special type of SU) serve as substrate for an SU or set of SUs. A simple and
      parameter sparse approximation is presented for the production rate of a
      generalized compound, i.e. a rich mixture of compounds that does not change in
      composition. An analysis of Droop's data on the growth of a haptophyte on
      phosphate and vitamin B(12) reserves illustrates the application of SUs.

PMID- 17029723
TI  - Orally disintegrating olanzapine for the treatment of a manic patient with
      esophageal stricture plus chronic pharyngitis.
AB  - An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is
      designed to dissolve rapidly upon contact with saliva. We describe a manic
      patient who has an esophageal stricture and chronic pharyngitis, two conditions
      that impede the swallowing of medications. She was successfully treated for her
      mania with this orally disintegrating formulation. This case report shows that
      ODT olanzapine may be useful in the psychiatric management of manic and other
      patients for whom olanzapine is appropriate, and who have an underlying medical
      condition that impedes swallowing oral medications.

PMID- 17029724
TI  - Multistage graph-based segmentation of thoracoscopic images.
AB  - This paper presents a graph-based segmentation method using multiple criteria in
      successive stages to segment thoracoscopic images acquired during a diskectomy
      procedure commonly used for thoracoscopic anterior release and fusion for
      scoliosis treatment. Starting with image pre-processing, including Gaussian
      smoothing, brightness and contrast enhancement, and histogram thresholding, a
      standard graph-based method is applied to produce a coarse segmentation of
      thoracoscopic images. Next, regions are further merged in a multistage graph
      based process based on features like grey-level similarity, region size and
      common edge length. Experimental results show that our approach achieves good
      spatial coherence, accurate edge location and appropriate segmentation of the
      regions of interest from a sequence of thoracoscopic images.

PMID- 17029725
TI  - Placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans, and
      biphenyls in Taiwanese mothers in relation to menstrual cycle characteristics.
AB  - The aim was to determine the body burden of dioxins and polychlorinated biphenyls
      (PCBs) and whether they are associated with variables influencing reproduction.
      Our subjects were healthy women (mean age of 29 [SD=4.5]) from central Taiwan.
      The congeners of dioxins and dioxin-like PCBs in placentas (n=119) were
      identified using gas chromatography/high resolution mass spectrometry. The median
      levels of polychlorinated dibenzo-p-dioxins/dibenzofurans and PCBs were 10.2
      (geometric mean [GM]: 9.8, 95% confidence interval [95% CI]: 8.8-10.9) and 2.7
      (GM: 2.7, 95% CI: 2.3-3.1) pg WHO-TEQ/g lipid, respectively. Total TEQ level in
      placentas was significantly correlated with mothers' arm circumference (r=0.22,
      p=0.043). Increased body fat percentage was associated with higher total TEQ
      level in placentas. After adjustment for maternal age, pre-pregnant body mass
      index (BMI), and parity, placental dioxin-TEQ level higher in women (age 19
      years) with irregular menstrual cycle than in those (age <18 years) with regular
      menstrual cycle (p=0.032) and placental PCB-TEQ level was higher in women with
      menstrual cycles longer than 33 days versus less than 33 days (p=0.006). Thus,
      environmental exposure to dioxins and PCBs may be related to changes in current
      menstrual cycle characteristics.

PMID- 17029726
TI  - Abrogation of streptococcal pyrogenic exotoxin B-mediated suppression of
      phagocytosis in U937 cells by Cordyceps sinensis mycelium via production of
      cytokines.
AB  - Streptococcal pyrogenic exotoxin B (SPE B) is a virulent factor in group A
      streptococcal infection. We previously showed that SPE B reduced phagocytosis in
      human monocytic U937 cells. Here we show that the mycelium extract of Cordyceps
      sinensis (CS), a Chinese immunomodulatory herbal medicine, increased phagocytosis
      in U937 cells. Neither heat nor trypsin pretreatment prevented CS extract from
      causing this increase. Further studies indicated that SPE B-mediated suppression
      of U937 cell phagocytic activity was abrogated by CS extract. Factors in the
      conditioned medium from CS-extract-treated U937 cells were responsible for
      blocking the SPE B-mediated suppression of phagocytosis. Heating the conditioned
      medium eliminated the increase, which suggested that the U937-cell protein
      products augmented phagocytosis. Analyzing cytokine mRNA expression of U937 cells
      revealed increases in interferon-gamma (IFN-gamma), interleukin (IL)-12 p35 and
      p40, and tumor necrosis factor-alpha (TNF-alpha), but not in IL-1beta, IL-6, or
      IL-8. Treating U937 cells with anti-IFN-gamma, IL-12, and TNF-alpha antibodies
      also eliminated the conditioned medium-induced increase in phagocytosis. Taken
      together, SPE B inhibited phagocytosis, but CS mycelium extract abrogated this
      inhibition by causing cytokine production.

PMID- 17029727
TI  - Molecular orbital study of porphyrin-substrate interactions in cytochrome P450
      catalysed aromatic hydroxylation of substituted anilines.
AB  - The reaction mechanism for the primary reaction step of the hydroxylation of 3
      fluoro-6-methylaniline, attacked at different positions (oxygen attack across a C
      C bond and direct attack at positions para and ortho with respect to the NH(2)
      group) catalysed by a high-valent ferryl-oxo porphyrin a(2u)-cation complex with
      H(3)CS(-) as an axial ligand, has been investigated on the basis of electronic
      structure calculations in local spin-density approximation. Non-repulsive
      potential curves are obtained only in cases of direct attack at the para- and
      ortho-positions with respect to NH(2), but not for epoxide formation. Comparing
      the potential curves for the hydroxylation at the positions para and ortho to the
      NH(2)-group, an attack at the para-position is more likely. The relative
      orientation of the substrate towards the porphyrin is essentially determined by
      the interaction between the substituents of the substrate and the porphyrin.
      Consequently, different geometrical orientations of the substrate are obtained
      for hydroxylation at the para- and ortho-positions. In both cases of direct
      attack the substrate plane is not parallel to the porphyrin plane. The decisive
      role of sulphur in the hydroxylation is demonstrated by the participation of the
      S(3p)-orbitals in all molecular orbitals involved in the reaction.

PMID- 17029728
TI  - Ortho-aminobenzoic acid as a fluorescent probe for the interaction between
      peptides and micelles.
AB  - Ortho-aminobenzoic acid (o-Abz) has been used as a fluorescent probe in
      internally quenched fluorescent peptides for continuous protease assays. We
      investigated the fluorescent properties of the probe in order to verify if it can
      be used to monitor the interaction of peptides with micelles. Abz-aminoacyl
      monomethyl amides (Abz-Xaa-NHCH(3), where Xaa=Arg, Phe, Leu and Glu) were
      synthesized. Quantum yield, spectral position, anisotropy and lifetime decay were
      analyzed in the presence and absence of sodium dodecyl sulfate (SDS) micelles.
      Significant changes in the fluorescence parameters were observed for Abz-Arg
      NHCH(3) in comparison to Abz-Glu-NHCH(3), indicating a strong electrostatic
      component in the compound's interaction with the negative charged micelles. The
      change in fluorescence parameters, observed when the probe is bound to
      hydrophobic amino acids Abz-Phe-NHCH(3) and Abz-Leu-NHCH(3), is probably due to
      insertion of those compounds into micelles. Abz-NHCH(3) fluorescence is less
      affected by the presence of micelles, indicating that the occurrence of
      interaction is dependent on the properties of the amino acid to which the
      fluorophore is attached. The quenching data with acrylamide confirmed these
      results. Titration curves allowed the estimation of association constants between
      Abz compounds and SDS, according to a single partition model. Although the
      results cannot be strictly applied to the titration with charged compounds, it
      was verified that the association constant for the isolated Abz-NHCH(3) is
      significantly lower than those for Abz-Phe-NHCH(3) and Abz-Leu-NHCH(3). It is
      concluded that the Abz group is a sensitive and convenient fluorescent probe to
      monitor peptide binding to amphiphilic aggregates. That conclusion is supported
      by measurements with the peptide Abz-Leu-Arg-Phe-NH(2).

PMID- 17029729
TI  - Self-assembly of melanin studied by laser light scattering.
AB  - The unknown molecular weight and chemical structure of melanin place the study of
      these pigments outside the range of the classical biochemical techniques; thus in
      this paper the problem of characterizing these heterogeneous biopolymers was
      approached by means of light scattering techniques, static and dynamic. The
      static technique allowed us to identify the macromolecular properties (MW and
      R(g)(2)(1/2)) of melanin extracted from sepia inksac and of two synthetic
      analogues: L-Dopa melanin obtained by autooxidation and by enzymatic oxidation by
      Tyrosinase. By dynamic light scattering (DLS), the hydrodynamic radius R(h) was
      measured to monitor the temporal behaviour of the polymerization and aggregation
      processes and R(h) variation by changing the chemical constraints of the
      polymerization medium, such as pH and ionic strength. The fractal dimension d of
      the aggregates of melanin, both natural and synthetic, in the past only
      recognized during the aggregation of the synthetic one by lowering the pH of the
      medium, was a useful parameter to further investigate and compare the structure
      of melanin granules of differing origins, revealing for the natural sample, a
      structure with clusters that are spherical, not largely hydrated and self
      assembled, following a reaction limited aggregation kinetics (d=2.38).

PMID- 17029730
TI  - Folding under inequilibrium conditions as a possible reason for partial
      irreversibility of heat-denatured proteins: computer simulation study.
AB  - Using computer simulations we have studied possible effects of heating and
      cooling at different scan rates on unfolding and refolding of macromolecules. We
      have shown that even the simplest two-state reversible transition can behave
      irreversibly when an unfavorable combination of cooling rate, relaxation time and
      activation energy of refolding occurs. On the basis of this finding we suppose
      that apparent irreversibility of some proteins denatured by heat may result from
      slow relaxation on cooling rather than thermodynamic instability and/or
      irreversible alterations of the polypeptide chain. Using this kinetic reversible
      two-state model, we estimated the effects of the scan rate and kinetic parameters
      of the macromolecule on its unfolding-refolding process. A few recommendations
      are suggested on how to reach maximal possible recovery after denaturation if
      refolding appears to be under kinetic control.

PMID- 17029731
TI  - The impact of abnormal autoimmune function on reproduction: maternal and fetal
      consequences.
AB  - The impact of abnormal autoimmune function on reproductive success has remained a
      highly controversial issue. This is, at least partially, due to the relative lack
      of demographic data from women with established autoimmune diseases. We,
      therefore, investigated 163 women with proven autoimmune diseases and 73 controls
      in a demographic study of reproductive success and impact of abnormal
      autoimmunity on pregnancy and offspring. Women with autoimmune diseases
      experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses
      (p=0.05). Offspring from women with autoimmune diseases demonstrated a
      significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR
      3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet
      confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with
      autoimmune diseases exhibited a trend towards lower cesarean section delivery
      during their own birth and a significantly increased prevalence of disease in
      vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune
      diseases impair female fecundity even before the diseases become clinically
      overt. Offspring are at increased risk to develop autoimmune diseases, though
      they may differ from those of their mothers. This risk appears to correlate with
      mode of delivery and may be the consequence of varying cell traffic dynamics with
      vaginal and cesarean section deliveries.

PMID- 17029732
TI  - Flexibility of DNA in complex with proteins deduced from the distribution of
      bending angles observed by scanning force microscopy.
AB  - Flexibility and dynamics of DNA are important for DNA-binding and recognition by
      proteins. Here the flexibility of DNA is calculated from the distribution of DNA
      bending angles of single DNA molecules as observed by scanning force microscopy
      by applying an equation that links the force constant of DNA-bending (f) to the
      variance of the distribution of bending angles (sigma): f=RT/sigma(2). Using
      published data, f is calculated to be 3-5 J/degree(2) for free DNA. Thus, bending
      DNA by 20 degrees requires approx. 0.5-1 kJ/mol. This result shows that DNA is
      very flexible and readily can be bent by thermal motion. DNA-flexibility is not
      altered in some protein-DNA complexes (HhaI methyltransferase, EcoRV restriction
      endonuclease). In contrast, DNA-binding by EcoRI endonuclease increases DNA
      flexibility and binding by EcoRI methyltransferase restricts the flexibility of
      DNA. During the transition of the RNA polymerase-sigma(54)-DNA complex from the
      closed to the open form and of cro repressor from a non-specific to a specific
      binding mode the flexibility of the DNA is strongly reduced.

PMID- 17029733
TI  - Thermodynamics of aliphatic and aromatic hydrocarbons in water.
AB  - Makhatadze and Privalov have analyzed the thermodynamics of transfer of aliphatic
      and aromatic hydrocarbons from the gas phase into water. Finding that the
      hydration free energy of aliphatic and aromatic hydrocarbons have different
      signs, they conclude that the mechanism causing hydrophobicity of these solutes
      is of a different nature. Here, we offer an alternative analysis of the
      dissolution of these non-polar compounds into water based on a recently published
      interpretation scheme for thermodynamic transfer functions. Our analysis shows
      that the hydrophobicity of aromatic and aliphatic hydrocarbons is qualitatively
      the same, i.e. its causes are the same namely the extremely high cohesive energy
      of water which overcomes the favorable solute-solute and solute-water
      interactions. However, both analyses conclude that the experimentally observed
      quantitative difference between the interactions of water with aliphatic and
      aromatic hydrocarbons, can be assigned to the formation of aromatic ring-water H
      bonds.

PMID- 17029734
TI  - TRP proteins and cancer.
AB  - Cancer is the second most common cause of death in western countries. It is
      therefore of fundamental importance to improve the treatment of patients with
      malignant tumors. This goal can only be achieved if we get closer insight in the
      various mechanisms leading to tumor formation. Significant progress in the
      understanding of carcinogenesis has been made during the last couple of years.
      Ion channels contribute to the regulation of cell proliferation which has
      initially been shown for K+ channels. Meanwhile, other ion channels such as Cl-,
      Na+ and Ca2+ channels seem to influence cellular function like growth, migration
      and invasion. In addition, cation channels of the transient receptor potential
      (TRP) superfamily are implicated in cancer formation. Most recent data concerning
      TRP vanilloid (TRPV) type 6, TRP melastatin (TRPM) type 1 and 8 channels and
      their relevance for common human cancer types will be highlighted in this review.
      Furthermore, TRP channel structure and function will be discussed in the light of
      their possible importance as prognostic markers and targets for drug discovery.

PMID- 17029735
TI  - Differential activation of the JNK signal pathway by UV irradiation and glucose
      deprivation.
AB  - Exposure of mammalian cells to ultraviolet (UV) light or glucose deprivation
      activates c-Jun NH2-terminal protein kinase (JNK). However, the exact mechanism
      by which UV induces JNK activation is not yet understood completely. Previously,
      we have observed that glucose deprivation activates the ASK1-SEK1-JNK signal
      transduction pathway. In the present study, we reveal that UVC irradiation
      induced JNK activation has a different signal transduction pathway from glucose
      deprivation. UVC irradiation increases the interaction between JIP3 and MEKK1,
      SEK1, while glucose deprivation increases the interaction between JIP3 and ASK1,
      SEK1, and JNK. UVC irradiation activates MEKK1 rather than ASK1. We also observed
      that MEKK1 interacted with Grb2 and Grb2-MEKK1 complex was recruited to epidermal
      growth factor receptor (EGFR) after UVC irradiation. Taken together, our data
      demonstrate that UVC-induced JNK activation adopts a different signaling cascade
      (EGFR-Grb2-MEKK1-SEK1-JNK) from glucose deprivation (ASK1-SEK1-JNK).

PMID- 17029736
TI  - Medical countermeasures to WMDs: defence research for civilian and military use.
AB  - This document will address the contributions of defence research to both military
      and civilian applications. Compared to civilian research capabilities,
      particularly in terms of personnel, defence research resources are limited.
      Additionally, many of the research targets are either classified or involve
      applications that have (or had) limited civilian use. Recently, however, spurred
      by counter-terrorism preparedness particularly in North America, many previously
      'orphaned' research projects have assumed much greater prominence. This has
      occurred in all areas of militarily significant research, but this paper will
      focus on medical countermeasures to weapons of mass destruction and to a lesser
      extent on detection/identification issues. In the area of countermeasures to
      chemical weapons, most of the defence research has been devoted to "classical"
      CWAs such as nerve agents, vesicants, choking and blood agents, with considerable
      success in some applications. Similarly vaccination programs for the biological
      weapons have also been quite successful. And recent attention has been directed
      toward the "emerging" threats such as some of the exquisitely lethal toxins. The
      difference now is that all of these research programs have the objective of
      moving from research to development of not only military but also civilian use
      very much sooner than later.

PMID- 17029737
TI  - Determination of protein association constants by electrophoresis.
AB  - An electrophoresis cell with scanning UV-absorption optics is presented. It
      allows the measurement of moving reaction boundaries of dilute protein solutions
      with a high-resolution. The protein profiles in the boundaries can be
      extrapolated to infinite time after an appropriate transformation of space and
      time coordinates and then evaluated with respect to association constants. This
      is demonstrated for the dimer-tetramer equilibrium of haemoglobin.

PMID- 17029738
TI  - Solvent isotope effect on thermodynamics of hydration.
AB  - Partial molar heat capacities of five linear alcohols (methanol, ethanol, n
      propanol, n-butanol, n-pentanol) and five N-substituted amides (n-propionamide, N
      methylformamide, N-methylacetamide, N-methylpropionamide, N-ethylacetamide) in
      aqueous D(2)O solution have been measured at 25 degrees C. The heat capacities of
      transfer of these compounds from H(2)O to D(2)O were calculated using previously
      reported (Makhatadze et al., Biophys. Chem. 64 (1997) 93) values of partial heat
      capacities of alcohols and amides in aqueous H(2)O solutions. It is shown that
      the sign and magnitude of the heat capacity change upon transfer from H(2)O to
      D(2)O depends on the relative amount of polar and non-polar solvent accessible
      surface areas of solute. Analysis shows that transfer of non-polar surface from
      H(2)O to D(2)O is accompanied by a positive heat capacity change. In contrast,
      transfer of polar surface from H(2)O to D(2)O occurs with negative heat capacity
      change. Estimates show that the solvent isotope effect on the heat capacity
      changes upon protein unfolding can be predicted using the changes of the polar
      and non-polar surface area changes upon protein unfolding and the transfer data
      of model compounds. Analysis of the thermodynamic functions of transfer of non
      polar compounds from H(2)O to D(2)O shows puzzling behavior which contradicts
      current definitions of the hydrophobic effect.

PMID- 17029739
TI  - Bead modeling using HYDRO and SOLPRO of the conformation of multisubunit
      proteins: sunflower and rape-seed 11S globulins.
AB  - Oil seed globulins from sunflower and rape seed are multi-subunit, oligomeric
      proteins whose native 11S form is a hexamer. In this work we try to determine the
      spatial structure in which the six subunits of 11S globulin are arranged.
      Experimental values of solution properties, including radius of gyration,
      sedimentation and diffusion coefficients and intrinsic viscosity, are compared
      with theoretical predictions for hexamers of various geometries. Bead model
      calculations of solution properties are carried out using the HYDRO and SOLPRO
      computer programs. A most compact shape, the regular octahedron, is the hexameric
      structure that fits best the experimental values.

PMID- 17029740
TI  - The 'Janus' nature of proteins: systems at the verge of the microscopic and
      macroscopic world.
AB  - Direct measurement of the heat capacity of proteins by microcalorimetry has had a
      decisive impact on understanding the behaviour of these biopolymers. Statistical
      mechanics allow a straightforward calculation and prediction of the enthalpy and
      heat capacity curves from the partition function. We show that these predictions
      can differ from the more intuitive models used so far for the description of the
      thermodynamic behaviour of proteins if the transition involves a stoichiometry
      other than 1:1. Furthermore, we delineate that the characteristics of protein
      unfolding are governed by the fluctuations associated with the small size of
      these molecules. Therefore it may be necessary to modify the picture of the
      unfolding of small proteins in the light of statistical physics, while for very
      large proteins the current view may be maintained as a useful limiting
      approximation.

PMID- 17029741
TI  - Effect of levetiracetam on visual-spatial memory following status epilepticus.
AB  - Status epilepticus (SE) is often followed by severe cognitive impairment,
      including memory impairment. Previous studies have shown that SE is associated
      with impairment of single cells in the hippocampus that fire action potentials
      when the animal is in a specific location in space, the so-called place cells,
      and that place cell function correlates well with performance in tasks of visual
      spatial memory. Place cell patterns therefore appear to be an excellent measure
      of spatial memory and may serve as a tool to assess seizure-induced impairment in
      memory. In this study we determined the relationship between visual-spatial
      memory and place cell function following SE. In addition, we determined if
      levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can
      improve cognitive function and place cell firing patterns when administered
      following SE. SE was induced in adult male rats which were then randomized to
      post-SE treatment with LEV or normal saline (NS) treatment for 14 days. Non-SE
      control rats also were randomized to LEV or NS. Following discontinuation of LEV
      rats were tested for visual-spatial memory in the Morris water-maze and then
      underwent unit recording in the CA1 region of the hippocampus. Brains were then
      evaluated for cell loss and mossy fiber sprouting. SE was associated with
      severely impaired performance in the water-maze with SE rats demonstrating no
      learning over four days of testing. Paralleling this memory deficit was a marked
      disturbance in firing patterns of pyramidal neurons in CA1. Non-SE rats learned
      quickly over four days of water-maze testing and had normal pyramidal cell firing
      patterns. LEV had no major effects on water-maze performance or place cell
      function. Histopathological examination of the brains showed severe cell loss in
      CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV
      treatment resulted in less histological damage in the hippocampus but had no
      effect on visual-spatial function or place cell physiology in either control or
      SE rats.

PMID- 17029742
TI  - Characterisation of the fibrinogenolytic properties of the buccal gland secretion
      from Lampetra japonica.
AB  - Lampetra japonica is representative of the ancient cyclostomota class of animals,
      and its buccal gland secretion (called lamphredin) is known to act as an
      anticoagulant. In this study, it was observed by both native-PAGE and SDS-PAGE
      that the secretion mainly contained two protein bands, buccal gland secretion
      protein-1 (BGSP-1, 159,909 Da) and buccal gland secretion protein-2 (BGSP-2,
      25,660 Da). The N-terminal amino acids of BGSP-1 (EAESF QNLKT RICGG LNGLG) and
      BGSP-2 (TSVND WKLLD TKLSA NRKVI) were sequenced. Using a Sephadex G-75 column, we
      isolated BGSP-1, BGSP-2 and small peptides from the buccal gland secretion, but
      found only BGSP-1 showed fibrinogenolytic activity. BGSP-1 and lamphredin were
      found to rapidly degrade the alpha chain of human fibrinogen, slowly degrade the
      beta chain and hardly degrade the gamma chain. BGSP-1 and lamphredin showed a
      similar map by SDS-PAGE for the degradation of fibrinogen by cleavage at Ala(10)
      Glu(11) and His(368)-Ser(369). BGSP-1 was also found to hydrolyze neuronal
      protein tau at Glu(12)-Asp(13) and Gln(244)-Thr(245). Further study showed that
      lamphredin and BGSP-1 were inactivated in the presence of a metal chelating agent
      EDTA. However, addition of Ca(2+) or Mg(2+) but not Zn(2+) restored the
      fibrinogenolytic activity. This suggests that BGSP-1 acts in the buccal gland as
      a metalloproteinase with a broad substrate specificity. Furthermore, the
      secretion showed cytolytic properties towards human SH-SY5Y and HeLa cells in
      culture, and lamphredin at a 50-fold dilution induced cell death.

PMID- 17029743
TI  - Purification and functional characterization of AAV1, a novel P-III
      metalloproteinase, from Formosan Agkistrodon acutus venom.
AB  - AAV1, an alkaline glycoprotein (GP), was purified from Agkistrodon acutus venom
      by two chromatographic steps on successive DEAE-Sephadex A-50 and Superdex 75
      FPLC columns. AAV1 on SDS-PAGE under non-reducing conditions migrated as a
      monomeric and a polymeric forms with apparent molecular mass of 57 and 180 kDa,
      respectively. Upon reduction, it appeared as a single broad band with a mass of
      50.3 kDa corresponding to the size of a typical P-III metalloproteinase
      acurhagin. The N-terminal sequence of an autoproteolytical 30 kDa-fragment of
      AAV1 showed a high homology to that of venom proteins with Metalloproteinase,
      Disintegrin-like, and Cysteine-rich (MDC) domains. Although it was devoid of
      cleaving activity toward gelatin, fibronectin and prothrombin, AAV1
      preferentially digested the Aalpha chain of fibrinogen and followed by the Bbeta
      chain, leading to the inhibition of fibrinogen-induced platelet aggregation in
      elastase-treated human platelets. However, the proteolytic activity of AAV1 was
      completely inactivated by the chelating agent but not serine proteinase
      inhibitor. Furthermore, AAV1 could concentration-dependently inhibit platelet
      aggregation and suppress tyrosine phosphorylation of intracellular proteins in
      collagen- and convulxin-stimulated platelets, respectively. The interaction of
      MDC domains in AAV1 molecule with platelet GPVI was responsible for the
      inhibitory effect of AAV1 on collagen- and convulxin-induced platelet
      aggregation. Taken together, these pieces of evidence suggest that AAV1 from
      Formosan viper venom belongs to a new member of high-molecular mass
      metalloproteinase family and functions as a GPVI antagonist.

PMID- 17029745
TI  - Experimental data and modelling of apparent molar volumes, isentropic
      compressibilities and refractive indices in aqueous solutions of glycine + NaCl.
AB  - Experiments have been performed at 298.15 K to measure the density, sound
      velocity and refractive index of glycine in aqueous solutions of NaCl over a wide
      range of both glycine and NaCl concentrations. The values of apparent molar
      volume and isentropic compressibility of glycine were calculated from the
      measured data. The results show a positive transfer volume of glycine from an
      NaCl solution to a more concentrated NaCl solution. This indicates that the size
      of a glycine molecule is larger in a solution with higher NaCl concentration. The
      negative values of apparent isentropic compressibility imply that the water
      molecules around the glycine molecules are less compressible than the water
      molecules in the bulk solution. These effects are attributed to the doubly
      charged behaviour of glycine and to the formation of physically bonded ion-pairs
      between the charged groups of glycine and sodium and chloride ions. The formation
      of ion-pairs, whose extents of binding reactions depend on the concentrations of
      both NaCl and glycine, alter the hydration number of glycine. This also explains
      the reason for the increase in the size of glycine with an increase in the NaCl
      concentration. A model based on the Pitzer formalism has been developed to
      correlate the activity coefficient, apparent molar volume and isentropic
      compressibility of glycine in aqueous solutions of NaCl. The results show that
      the model can accurately correlate the interactions in aqueous solutions of
      glycine and NaCl.

PMID- 17029744
TI  - Equilibrium unfolding of DLC8 monomer by urea and guanidine hydrochloride:
      Distinctive global and residue level features.
AB  - We present circular dichroism (CD), steady state fluorescence and
      multidimensional NMR investigations on the equilibrium unfolding of monomeric
      dynein light chain protein (DLC8) by urea and guanidine hydrochloride (GdnHCl).
      Quantitative analysis of the CD and fluorescence denaturation curves reveals that
      urea unfolding is a two-state process, whereas guanidine unfolding is more
      complex. NMR investigations in the native state and in the near native states
      created by low denaturant concentrations enabled residue level characterization
      of the early structural and dynamic perturbations by the two denaturants.
      Firstly, (15)N transverse relaxation rates in the native state indicate that the
      regions around N10, Q27, the loop between beta2 and beta4 strands, and K87 at the
      C-terminal are potential unfolding initiation sites in the protein. Amide and
      (15)N chemical shift perturbations indicate different accessibilities of the
      residues along the chain and help identify locations of the early perturbations
      by the two denaturants. Guanidine and urea are seen to interact at several sites
      some of which are different in the two cases. Notable among the common
      interaction site is that around K87 which is in close proximity to W54 on the
      protein structure, but the interaction modes of the two denaturants are
      different. The secondary chemical shifts indicate that the structural
      perturbation by 1M urea is small, compared to that by guanidine which is more
      encompassing over the length of the chain. The probable (phi, psi) changes at the
      individual residues have been calculated using the TALOS algorithm. It appears
      that the helices in the protein are significantly perturbed by guanidine.
      Further, comparison of the spectral density functions of the native and the two
      near native states in the two denaturants implicate greater loosening of the
      structure by guanidine as compared to that by urea, even though the structures
      are still in the native state ensemble. These differences in the early
      perturbations of the native state structure and dynamics by the two denaturants
      might direct the protein along different pathways, as the unfolding progresses on
      further increasing the denaturant concentration.

PMID- 17029746
TI  - Coexistence of multiple propagating wave-fronts in a regulated enzyme reaction
      model: link with birhythmicity and multi-threshold excitability.
AB  - We analyze the spatial propagation of wave-fronts in a biochemical model for a
      product-activated enzyme reaction with non-linear recycling of product into
      substrate. This model was previously studied as a prototype for the coexistence
      of two distinct types of periodic oscillations (birhythmicity). The system is
      initially in a stable steady state characterized by the property of multi
      threshold excitability, by which it is capable of amplifying in a pulsatory
      manner perturbations exceeding two distinct thresholds. In such conditions, when
      the effect of diffusion is taken into account, two distinct wave-fronts are shown
      to propagate in space, with distinct amplitudes and velocities, for the same set
      of parameter values, depending on the magnitude of the initial perturbation. Such
      a multiplicity of propagating wave-fronts represents a new type of coexistence of
      multiple modes of dynamic behavior, besides the coexistence involving, under
      spatially homogeneous conditions, multiple steady states, multiple periodic
      regimes, or a combination of steady and periodic regimes.

PMID- 17029747
TI  - Magnetic field perturbations as a tool for controlling enzyme-regulated and
      oscillatory biochemical reactions.
AB  - The feasibility of magnetic field perturbations as a tool for controlling enzyme
      regulated and oscillatory biochemical reactions is studied. Our approach is based
      on recent experimental results that revealed magnetic field effects on the in
      vitro activity of enzyme systems in accordance with the radical pair mechanism. A
      minimum model consisting of two coupled enzyme-regulated reactions is discussed
      that combines, in a self-consistent manner, magnetic field-sensitive enzyme
      kinetics with non-linear dynamical principles. Furthermore, a simple detector
      mechanism is described that is capable of responding to an oscillatory input.
      Results reveal that moderate-strength magnetic fields (B=1-100 mT) may
      effectively alter the dynamics of the system. In particular, a response behavior
      is observed that depends on: (1) the combination of static and time-varying
      magnetic fields; (2) the field amplitude; and (3) the field frequency in a non
      linear fashion. The specific response behavior is critically determined by the
      biochemical boundary conditions as defined by the kinetic properties of the
      system. We propose an experimental implementation of the results based on the
      oscillatory peroxidase-oxidase reaction controlled by the enzyme horseradish
      peroxidase.

PMID- 17029748
TI  - Intermembrane distance in multilamellar vesicles of phosphatidylcholine depends
      on the interaction free energy between solvents and the hydrophilic segments of
      the membrane surface.
AB  - To investigate the interaction of the surface of biomembranes with solvents
      systematically, we have studied the structure and phase behavior of multilamellar
      vesicles of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) in dimethylformamide (DMF)-water mixture by X-ray
      diffraction and differential scanning calorimetry. The solubility of
      phosphorylcholine, which is the same molecular structure as the head-group of
      phosphatidylcholine (PC), decreased with an increase in DMF concentration. This
      result indicates that DMF is a poor solvent for the hydrophilic segments of the
      surface of the PC membrane, and interaction free energy of the hydrophilic
      segments of the membrane surface with solvents increases with an increase in DMF
      concentration. X-ray diffraction data indicated that DPPC-MLVs were in the
      bilayer gel phase from 0 to 80% (v/v) DMF, and that the spacing (lamellar repeat
      period) and intermembrane distance of DPPC-MLV decreased with an increase in DMF
      concentration. Main transition temperature and pre-transition temperature of DPPC
      MLV increased with an increase in DMF concentration, and above 50% (v/v) DMF
      there was no pre-transition. In the interaction of POPC-MLV with DMF, X-ray
      diffraction data indicated that POPC-MLVs were in L(alpha) phase (liquid
      crystalline phase) from 0 to 80% (v/v) DMF, and that the spacing and
      intermembrane distance of POPC-MLV decreased with an increase in DMF
      concentration. These results are discussed by the change of the interaction free
      energy between the hydrophilic segments of the membrane surface and solvents. As
      DMF concentration increases, this interaction free energy may increase, resulting
      in the decrease of the intermembrane distance of PC-MLVs.

PMID- 17029749
TI  - The relationship between performance and fMRI signal during working memory in
      patients with schizophrenia, unaffected co-twins, and control subjects.
AB  - While behavioral research shows working memory impairments in schizophrenics and
      their relatives, functional neuroimaging studies of patients and healthy controls
      show conflicting findings of hypo- and hyperactivation, possibly indicating
      different relationships between physiological activity and performance. In a
      between-subjects regression analysis of fMRI activation and performance, low
      performance was associated with relatively lower activation in patients than
      controls, while higher performance was associated with higher activation in
      patients than controls in DLPFC and parietal cortex, but not occipital cortex,
      with unaffected twins of schizophrenics being intermediate between the groups.
      Accordingly, this supports the idea that both hyper and hypoactivation may be
      possible along a continuum of behavioral performance in a way consistent with a
      neural inefficiency model. Further, this study offers preliminary evidence that
      the relationship between behavior and physiology in schizophrenia may be
      heritable.

PMID- 17029750
TI  - The lymphotoxin Cys13Arg polymorphism and cognitive functioning in individuals
      with schizophrenia.
AB  - Genetic factors that modulate the immune response have been implicated as risk
      factors for schizophrenia and cognitive impairment. We assessed the correlation
      between cognitive functioning and the LTA Cys13Arg polymorphism in 351
      individuals with schizophrenia, 122 with bipolar disorder, and 160 controls.
      There was a significant association between cognitive functioning and the LTA
      Cys13Arg polymorphism within the schizophrenia (p<0.008) but not the other
      diagnostic groups. There was no association between cognitive functioning and the
      two other polymorphisms in the same gene complex. The LTA Cys13Arg polymorphism
      may represent a risk factor for cognitive impairment in individuals with
      schizophrenia.

PMID- 17029752
TI  - PSA-NCAM in mammalian structural plasticity and neurogenesis.
AB  - Polysialic acid (PSA) is a linear homopolymer of alpha2-8-N acetylneuraminic acid
      whose major carrier in vertebrates is the neural cell adhesion molecule (NCAM).
      PSA serves as a potent negative regulator of cell interactions via its unusual
      biophysical properties. PSA on NCAM is developmentally regulated thus playing a
      prominent role in different forms of neural plasticity spanning from embryonic to
      adult nervous system, including axonal growth, outgrowth and fasciculation, cell
      migration, synaptic plasticity, activity-induced plasticity, neuronal-glial
      plasticity, embryonic and adult neurogenesis. The cellular distribution,
      developmental changes and possible function(s) of PSA-NCAM in the central nervous
      system of mammals here are reviewed, along with recent findings and theories
      about the relationships between NCAM protein and PSA as well as the role of
      different polysialyltransferases. Particular attention is focused on
      postnatal/adult neurogenesis, an issue which has been deeply investigated in the
      last decade as an example of persisting structural plasticity with potential
      implications for brain repair strategies. Adult neurogenic sites, although
      harbouring all subsequent steps of cell differentiation, from stem cell division
      to cell replacement, do not faithfully recapitulate development. After birth,
      they undergo morphological and molecular modifications allowing structural
      plasticity to adapt to the non-permissive environment of the mature nervous
      tissue, that are paralled by changes in the expression of PSA-NCAM. The use of
      PSA-NCAM as a marker for exploring differences in structural plasticity and
      neurogenesis among mammalian species is also discussed.

PMID- 17029751
TI  - Insulin resistance index and counter-regulatory factors during olanzapine or
      risperidone administration in subjects with schizophrenia.

PMID- 17029753
TI  - Fate of transplanted nail matrical cells and potential of hard keratin production
      in vivo.

PMID- 17029754
TI  - The role of Pipelle Mark II sampling in endometrial disease diagnosis.
AB  - OBJECTIVE: To evaluate the feasibility and accuracy of Pipelle Mark II sampling
      (designed for combined cytology and histology testing) in the diagnosis of
      endometrial disease. MATERIALS AND METHODS: A 97 women with abnormal uterine
      bleeding or intrauterine lesions on ultrasound examination underwent Pipelle Mark
      II endometrial sampling, followed by diagnostic hysteroscopy. The adequacy of
      endometrial samples obtained for cytological and histological analysis was
      assessed. A correlation was established between endometrial cytology, histology
      and diagnostic hysteroscopy results. Where discrepancies were found, they were
      compared with the histological results obtained from operative hysteroscopy.
      RESULTS: The tissue samples obtained for cytological and histological diagnoses
      were insufficient in 14.4% and 11.3% of patients, respectively. The opposite was
      found in the group of postmenopausal women (N=52): the tissue samples for
      cytological and histological diagnoses were insufficient in only 3.8% and 15.4%
      of cases, respectively. The cytological results corroborated diagnostic
      hysteroscopy findings and histological results in all cases but 3 (3.6%). Only
      two cases of endometrial carcinoma were reported in this group of patients, and
      they were both detected by all three methods. The rate of false positives with
      endometrial cytological sampling was 3.6%. There were no false negatives.
      CONCLUSION: Pipelle Mark II endometrial sampling is feasible. It provides
      adequate samples for histological and/or cytological analysis and reliable
      results. It reduces the rate of false negative results for endometrial cancer.
      Pipelle Mark II sampling is particularly useful in postmenopausal women and in
      women with endometrial atrophy. Other larger studies are necessary to evaluate
      the efficiency of Pipelle Mark II.

PMID- 17029755
TI  - Prenatal sonographic findings in 207 fetuses with trisomy 21.
AB  - OBJECTIVE: The objective was to evaluate the contribution of second trimester
      ultrasound examination to the prenatal diagnosis of trisomy 21 in 207 fetuses
      with this aneuploidy. The type and frequency of abnormal sonographic findings
      were determined. Possible multiple malformation patterns, characteristic of
      trisomy 21 were sought. STUDY DESIGN: Singleton fetuses that had prenatal
      sonography during the second trimester, then underwent cytogenetic evaluation in
      our institution, made up the study population. The sonographic findings of 207
      fetuses with trisomy 21 were analyzed. RESULTS: Between 1990 and 2004, fetal
      karyotyping was performed in 22,150 patients for different indications. An
      abnormal karyotype was diagnosed in 514 cases (2.3%); among them 207 fetuses with
      trisomy 21 were detected (40.3%). Abnormal sonography was seen in 63.8% of the
      cases. Structural anomalies were detected in 28.5% of the trisomy 21 fetuses,
      among them cardiac defects (15.9%), central nervous system anomalies (14.5%), and
      cystic hygromas (6.8%) were the most common. Of the minor markers, increased
      nuchal translucency (28%), pyelectasis (20.3%), and shorter extremities (8.7%)
      were common findings. CONCLUSIONS: Appropriate diagnosis of structural anomalies,
      looking for relatively easily detectable minor markers and incorporating fetal
      echocardiography into the second trimester sonographic protocol, may increase the
      contribution of mid-trimester ultrasound examination to diagnosing trisomy 21.

PMID- 17029756
TI  - Assessment of factors contributing to changes in the incidence of antimicrobial
      drug resistance in Salmonella enterica serotypes Enteritidis and Typhimurium from
      humans in England and Wales in 2000, 2002 and 2004.
AB  - An investigation into changes in the occurrence of antimicrobial resistance in
      Salmonella enterica serotypes Enteritidis and Typhimurium from human infection in
      England and Wales in 2000, 2002 and 2004 has shown that the incidence of strains
      of S. Enteritidis with resistance to nalidixic acid coupled with decreased
      susceptibility to ciprofloxacin has more than doubled between 2000 and 2004,
      whereas the overall levels of resistance in S. Typhimurium have fallen by ca.
      25%. In relation to published data on veterinary sales of antimicrobials in the
      UK, the findings demonstrate that changes in the incidence of resistance do not
      correlate with changes in veterinary usage. For S. Enteritidis, important factors
      in the increased incidence of resistance were foreign travel and the consumption
      of imported foods contaminated with drug-resistant strains. For S. Typhimurium,
      the most important factor has been an overall decline in the occurrence of
      multiple drug-resistant S. Typhimurium definitive phage type 104. These studies
      have demonstrated that changes in the incidence of resistance in predominant
      salmonellas in humans in England and Wales from 2000 to 2004 are multifactorial.
      The findings also demonstrate that, in order to combat drug resistance in
      zoonotic salmonellas causing infections in humans, controls on the use of
      antibiotics in food animals analogous to those in operation in the UK should be
      implemented in countries that regularly import food into the UK.

PMID- 17029757
TI  - Radiocaesium accumulation in stemwood: integrated approach at the scale of forest
      stands for contaminated Scots pine in Belarus.
AB  - Twenty years after the Chernobyl accident, root uptake from the surface layers of
      contaminated forest soils plays a major role in radiocaesium ((137)Cs) transfer
      to the trees and accumulation in perennial compartments, including stemwood.
      Trustworthy long-term predictions (modelling) of stemwood contamination with
      (137)Cs should accordingly be based on a reliable picture of this source-sink
      relationship. Considering the complexity of the processes involved in (137)Cs
      cycling in forest stands, elementary ratios like transfer factors (TF) were shown
      to be not very relevant for that purpose. At the tree level, alternatives like
      the wood immobilisation potential (WIP) have therefore been proposed in order to
      quantify the current net (137)Cs accumulation in stemwood. Our objective was here
      to compare WIP values determined for a series of contaminated forest stands in
      Belarus with the corresponding pools of (137)Cs available in the soil for root
      uptake. The comparison reveals that both indices are quite proportional, whatever
      the forest ecosystem features. This corroborates the relevancy of WIP as an
      indicator of the current (137)Cs root uptake by the trees, which could
      accordingly help to improve the existing models of (137)Cs cycling and the long
      term management of contaminated forest ecosystems.

PMID- 17029758
TI  - Development and application of a GIS-based sediment budget model.
AB  - Accelerated erosion and increased sediment yields resulting from changes in land
      use are a critical environmental problem. Resource managers and decision makers
      need spatially explicit tools to help them predict the changes in sediment
      production and delivery due to unpaved roads and other types of land disturbance.
      This is a particularly important issue in much of the Caribbean because of the
      rapid pace of development and potential damage to nearshore coral reef
      communities. The specific objectives of this study were to: (1) develop a GIS
      based sediment budget model; (2) use the model to evaluate the effects of unpaved
      roads on sediment delivery rates in three watersheds on St. John in the US Virgin
      Islands; and (3) compare the predicted sediment yields to pre-existing data. The
      St. John Erosion Model (STJ-EROS) is an ArcInfo-based program that uses empirical
      sediment production functions and delivery ratios to quantify watershed-scale
      sediment yields. The program consists of six input routines and five routines to
      calculate sediment production and delivery. The input routines have interfaces
      that allow the user to adjust the key variables that control sediment production
      and delivery. The other five routines use pre-set erosion rate constants, user
      defined variables, and values from nine data layers to calculate watershed-scale
      sediment yields from unpaved road travelways, road cutslopes, streambanks,
      treethrow, and undisturbed hillslopes. STJ-EROS was applied to three basins on
      St. John with varying levels of development. Predicted sediment yields under
      natural conditions ranged from 2 to 7Mgkm(-2)yr(-1), while yield rates for
      current conditions ranged from 8 to 46Mgkm(-2)yr(-1). Unpaved roads are estimated
      to be increasing sediment delivery rates by 3-6 times for Lameshur Bay, 5-9 times
      for Fish Bay, and 4-8 times for Cinnamon Bay. Predicted basin-scale sediment
      yields for both undisturbed and current conditions are within the range of
      measured sediment yields and bay sedimentation rates. The structure and user
      interfaces in STJ-EROS mean that the model can be readily adapted to other areas
      and used to assess the impact of unpaved roads and other land uses sediment
      production and delivery.

PMID- 17029759
TI  - Collaborative environmental planning in river management: an application of
      multicriteria decision analysis in the White River Watershed in Vermont.
AB  - Multicriteria decision analysis (MCDA) provides a well-established family of
      decision tools to aid stakeholder groups in arriving at collective decisions.
      MCDA can also function as a framework for the social learning process, serving as
      an educational aid in decision problems characterized by a high level of public
      participation. In this paper, the framework and results of a structured decision
      process using the outranking MCDA methodology preference ranking organization
      method of enrichment evaluation (PROMETHEE) are presented. PROMETHEE is used to
      frame multi-stakeholder discussions of river management alternatives for the
      Upper White River of Central Vermont, in the northeastern United States.
      Stakeholders met over 10 months to create a shared vision of an ideal river and
      its services to communities, develop a list of criteria by which to evaluate
      river management alternatives, and elicit preferences to rank and compare
      individual and group preferences. The MCDA procedure helped to frame a group
      process that made stakeholder preferences explicit and substantive discussions
      about long-term river management possible.

PMID- 17029760
TI  - An analysis of functional neuroimaging studies of dorsolateral prefrontal
      cortical activity in depression.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is currently undergoing
      active investigation for use in the treatment of major depression. Recent
      research has indicated that current methods used to localize the site of
      stimulation in dorsolateral prefrontal cortex (DLPFC) are significantly
      inaccurate. However, little information is available on which to base a choice of
      stimulation site. The aim of the current study was to systematically examine
      imaging studies in depression to attempt to identify whether there is a pattern
      of imaging results that suggests an optimal site of stimulation localization. We
      analysed all imaging studies published prior to 2005 that examined patients with
      major depression. Studies reporting activation in DLPFC were identified. The
      DLPFC regions identified in these studies were analysed using the Talairach and
      Rajkowska-Goldman-Rakic coordinate systems. In addition, we conducted a
      quantitative meta-analysis of resting studies and studies of serotonin reuptake
      inhibitor antidepressant treatment. There was considerable heterogeneity in the
      results between studies. Changes in Brodmann area 9 were relatively consistently
      identified in resting, cognitive activation and treatment studies included in the
      meta-analysis. However, there was little consistency in the direction of these
      changes or the hemisphere in which they were identified. At this stage, the
      results of imaging studies published to date have limited capacity to inform the
      choice of optimal prefrontal cortical region for the use in rTMS treatment
      studies.

PMID- 17029761
TI  - Adsorption behaviour and surfactant elution of cationic salivary proteins at
      solid/liquid interfaces, studied by in situ ellipsometry.
AB  - Adsorption of the cationic salivary proteins lactoferrin, lactoperoxidase,
      lysozyme and histatin 5 to pure (hydrophilic) and methylated (hydrophobized)
      silica surfaces was investigated by in situ ellipsometry. Effects of
      concentration (</=10 microgml(-1), for lysozyme </=200 microgml(-1)) and
      dependence of surface wettability, as well as adsorption kinetics and elutability
      of adsorbed films by buffer and sodium dodecyl sulphate (SDS) solutions were
      investigated. Results showed that the amounts adsorbed decreased in the order
      lactoferrin>/=lactoperoxidase>lysozyme>/=histatin 5. On hydrophilic silica, the
      adsorption was most likely driven by electrostatic interactions, which resulted
      in adsorbed amounts of lactoferrin that indicated the formation of a monolayer
      with both side-on and end-on adsorbed molecules. For lactoperoxidase the adsorbed
      amounts were somewhat higher than an end-on monolayer, lysozyme adsorption showed
      amounts corresponding to a side-on monolayer, and histatin 5 displayed adsorbed
      amounts in the range of a side-on monolayer. On hydrophobized substrata, the
      adsorption was also mediated by hydrophobic interactions, which resulted in lower
      adsorbed amounts of lactoferrin and lactoperoxidase; closer to side-on monolayer
      coverage. For both lysozyme and histatin 5 the adsorbed amounts were the same as
      on the hydrophilic silica. The investigated proteins exhibited fast adsorption
      kinetics, and the initial kinetics indicated mass transport controlled behaviour
      at low concentrations on both types of substrates. Buffer rinsing and SDS elution
      indicated that the proteins in general were more tightly bound to the
      hydrophobized surface compared to hydrophilic silica. Overall, the surface
      activity of the investigated proteins implicates their importance in the salivary
      film formation.

PMID- 17029762
TI  - Light scattering in colloidal solution of magnetite in electric and magnetic
      fields.
AB  - Light scattering by magnetite particles in kerosene under the simultaneous action
      of crossed electric and magnetic fields was studied. Decreasing of variation of
      light scattering intensity at some values of electric and magnetic fields have
      been found. Values of fields at which a minimum of light scattering intensity
      occur depend on the angle between laser beam and the plane of crossed fields.

PMID- 17029763
TI  - [Severe malaria: assessment of the treatment of anaemia and cerebral
      manifestations in a tropical intensive cares unit].

PMID- 17029764
TI  - Advanced fuzzy cellular neural network: application to CT liver images.
AB  - OBJECTIVE: To achieve better boundary integrities and recall accuracies for
      segmented liver images, use of the advanced fuzzy cellular neural network
      (AFCNN), as a variant of the fuzzy cellular neural network (FCNN), is proposed to
      effectively segment CT liver images. MATERIALS AND METHODS: In order to better
      utilize relevant contour and gray information from liver images, we have improved
      the FCNN [Wang S, Wang M. A new algorithm NDA based on fuzzy cellular neural
      networks for white blood cell detection. IEEE Trans Inform Technol Biomed, in
      press], which proved to be very effective for the segmentation of microscopic
      white blood cell images, to create the novel neural network, AFCNN. Its
      convergent property and global stability are proved. Based on the FCNN-based NDA
      algorithm [Wang S, Wang M. A new algorithm NDA based on fuzzy cellular neural
      networks for white blood cell detection. IEEE Trans Inform Technol Biomed, in
      press], we developed the AFCNN-based NDA algorithm, which we used to segment 5 CT
      liver images. For comparison, we also segmented the same 5 CT liver images using
      the FCNN-based NDA algorithm. RESULTS AND CONCLUSION: : AFCNN has distinct
      advantages over FCNN in both boundary integrity and recall accuracy. In
      particular, the performance index Binary_rate is generally much higher for AFCNN
      than for FCNN when applied to CT liver images.

PMID- 17029765
TI  - Solving satisfiability problems using a novel microarray-based DNA computer.
AB  - An algorithm based on a modified sticker model accompanied with an advanced MEMS
      based microarray technology is demonstrated to solve SAT problem, which has long
      served as a benchmark in DNA computing. Unlike conventional DNA computing
      algorithms needing an initial data pool to cover correct and incorrect answers
      and further executing a series of separation procedures to destroy the unwanted
      ones, we built solutions in parts to satisfy one clause in one step, and
      eventually solve the entire Boolean formula through steps. No time-consuming
      sample preparation procedures and delicate sample applying equipment were
      required for the computing process. Moreover, experimental results show the bound
      DNA sequences can sustain the chemical solutions during computing processes such
      that the proposed method shall be useful in dealing with large-scale problems.

PMID- 17029766
TI  - Permeability of the reconstructed human epidermis model Episkin in comparison to
      various human skin preparations.
AB  - The objective of this work was to compare the barrier function of the small
      diameter reconstructed human epidermis model Episkin (d=12 mm) to human skin in
      vitro. For that purpose a modification for the Franz diffusion cell (d=15mm) had
      to be developed so as to allow direct comparison with the following human skin
      preparations: Full thickness skin (FTS), split thickness skin (STS), heat
      separated epidermis (HSE), and trypsin isolated stratum corneum (TISC). Among the
      tested preparations, HSE appeared to be the most preferable due to its clear
      morphological structure and ease of preparation. The lipid profile of HSE and
      Episkin was analyzed and showed significant differences in terms of cholesterol,
      ceramides and triglycerides contents, whereas cholesterol esters and fatty acids
      were not different. Permeation data with HSE and Episkin were then gathered using
      caffeine and testosterone. Both test compounds permeated much faster through
      Episkin than through HSE. Moreover, opposed to Episkin, HSE differentiated
      between the two test compounds. In spite of the remarkable progress in developing
      RHEs in the past years at this time Episkin can obviously not yet fully replace
      human skin for in vitro permeability experiments.

PMID- 17029767
TI  - Phenotypic characterisation of mice with exaggerated and missing LH/hCG action.
AB  - In order to study the physiology and pathophysiology of gonadotrophin action, we
      have produced transgenic (TG) mice overexpressing human chorionic gonadotrophin
      (hCG) alpha and beta subunits (hCG+ mice) and knockout (KO) mice for the
      luteinising hormone receptor (LHR; LuRKO mice). The two extremes in LH function,
      i.e. strong LH/hCG stimulation and total blockade of this action, confirm
      numerous earlier concepts about LH function, but they also reveal new aspects
      about gonadal function during excessive LH production and in the absence of this
      trophic stimulus. The purpose of this review is to summarise the key findings on
      these two genetically modified mouse models.

PMID- 17029768
TI  - 1alpha,25-dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon
      cells.
AB  - The antimitotic and prodifferentiating 1alpha,25-dihydroxyvitamin D3 (1alpha,25
      (OH)2D3), synthesized at various extrarenal sites could potentially prevent
      sporadic tumor development. Physiological regulation of extrarenal Vitamin D
      hydroxylases following tissue accumulation of 1alpha,25-(OH)2D3 is unknown. We
      therefore investigated basal and Vitamin D-regulated expression and activity of
      the synthesizing (CYP27B1) and metabolizing (CYP24A1) hydroxylase in three cell
      lines derived from the colon, and compared this to cells from the prostate and
      mammary gland. Our results show that all cells, irrespective of origin and
      differentiation, express CYP27B1 mRNA, whereas basal CYP24A1 mRNA is highly
      expressed only in undifferentiated cells. Treatment with 1alpha,25-(OH)2D3
      diminishes CYP27B1 and Vitamin D receptor mRNA expression, but elevates CYP24A1
      mRNA to equal levels in all cells. As shown by HPLC, CYP27B1 is active only if
      basal 24-hydroxylation is not maximally functional. In turn, accumulation of
      1alpha,25-(OH)2D3 will induce 24-hydroxylation. We conclude that, although
      extrarenal and renal metabolic pathways for Vitamin D are similar, malignancy of
      tumor cells determines extent of Vitamin D catabolism.

PMID- 17029769
TI  - Eosinophilic pleural effusion after gastric variceal obliteration with
      cyanoacrylate.
AB  - Pleuropulmonary complications after endoscopic injection sclerotherapy for
      treatment of esophagogastric varices are not uncommon but are usually mild and
      self-limited. Herein we report a male patient with liver cirrhosis who underwent
      endoscopic injection sclerotherapy, using a mixture of n-butyl-2-cyanoacrylate
      and ethiodized oil for obliteration of gastric varices. After the procedure, he
      developed moderate amount of left pleural effusion that persisted for a period of
      time and required thoracentesis and medical treatment. We believed that the
      inadvertent retrograde reflux of the embolized glue and ethiodized oil via the
      portosystemic venous collateral into the left pleura might be the possible
      mechanism for the development of left pleural effusion as the droplets of
      ethiodized oil were seen along the left pleura on the imaging studies.

PMID- 17029770
TI  - Severe vocal cord dysfunction resistant to all current therapeutic interventions.
AB  - Vocal cord dysfunction (VCD) is characterised by paradoxical vocal cord adduction
      during inspiration or throughout the respiratory cycle, it results in wheeze,
      stridor, cough and dyspnoea. Although asthma and VCD can coexist, patients with
      VCD are frequently misdiagnosed with refractory asthma. It can severely restrict
      an individual's level of activity and effective therapeutic control can be
      difficult to achieve. We report the case of a patient who was treated with all
      available therapeutic interventions, including intralaryngeal botulinum toxin
      injection, but failure resulted in a permanent trachesotomy.

PMID- 17029771
TI  - The effect of fresh frozen plasma in severe closed head injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is one of the most common causes of
      morbidity and mortality. Coagulopathy, commonly occurring after severe TBI, is
      associated with poor outcome and secondary complications, especially delayed
      traumatic intracerebral hematoma (DTICH). In this study we evaluated the effect
      of fresh frozen plasma (FFP) on the reduction in the incidence of DTICH in severe
      closed head injury victims. METHODS: This study was carried out as a double-blind
      randomized clinical trial. Ninety patients were entered in two parallel groups
      taking either FFP or normal saline (N/S). Patients' selection criteria for both
      groups were: severe closed head injury (Glasgow coma scale < or =8), no mass
      lesion required evacuation and no history of coagulopathy. The clinical findings,
      laboratory data, computed tomography (CT) scans and Glasgow outcome scale after 1
      month were assessed and compared in two groups. RESULTS: Out of 90 patients, 44
      received FFP and 46 received N/S. The development of new intracerebral hematoma
      in follow-up CT scans were more common in the FFP group than the N/S group
      (p=0.012). Both groups showed similar frequency of poor outcome (p=0.343). The
      mortality was significantly more common in the FFP group than in the N/S group
      (63% versus 35%, p=0.006). CONCLUSION: The result of this study revealed that
      early empirical infusion of FFP in patients with severe head injury may lead to
      adverse effects, such as an increase in the frequency of DTICH and an increase in
      the mortality.

PMID- 17029774
TI  - Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell
      carcinoma.
AB  - Epigenetic mechanisms involving DNA methylation and chromatin remodeling are
      important in silencing tumor suppressor genes (TSG) in various malignancies,
      including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is
      a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1
      promoter with resultant gene silencing has been reported in several tumors, but
      not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the
      corresponding non-malignant tissues, and the correlation of DLC1 methylation with
      the clinicopathological characteristics of RCC patients. Although DLC1
      methylation and downregulation were only detected in one of seven RCC cell lines
      using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription
      PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC
      tumors, which was further confirmed by direct sequencing of MSP products and high
      resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non
      malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared
      to be a relatively early event during renal tumorigenesis since 33% of the RCC
      tumors with pT1 (TNM staging) showed methylation, which is similar to other late
      stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a
      subset of RCC tumors and may play a role in renal carcinogenesis.

PMID- 17029773
TI  - The E705K mutation in hPMS2 exerts recessive, not dominant, effects on mismatch
      repair.
AB  - The hPMS2 mutation E705K is associated with Turcot syndrome. To elucidate the
      pathogenesis of hPMS2-E705K, we modeled this mutation in yeast and characterized
      its expression and effects on mutation avoidance in mammalian cells. We found
      that while hPMS2-E705K (pms1-E738K in yeast) did not significantly affect hPMS2
      (Pms1p in yeast) stability or interaction with MLH1, it could not complement the
      mutator phenotype in MMR-deficient mouse or yeast cells. Furthermore, hPMS2
      E705K/pms1-E738K inhibited MMR in wild-type (WT) mammalian cell extracts or yeast
      cells only when present in excess amounts relative to WT PMS2. Our results
      strongly suggest that hPMS2-E705K is a recessive loss-of-function allele.

PMID- 17029775
TI  - Adsorption of malachite green on groundnut shell waste based powdered activated
      carbon.
AB  - In the present technologically fast changing situation related to waste
      management practices, it is desirable that disposal of plant waste should be done
      in a scientific manner by keeping in view economic and pollution considerations.
      This is only possible when the plant waste has the potential to be used as raw
      material for some useful product. In the present study, groundnut shell, an
      agricultural waste, was used for the preparation of an adsorbent by chemical
      activation using ZnCl2 under optimized conditions and its comparative
      characterisation was conducted with commercially available powdered activated
      carbon (CPAC) for its physical, chemical and adsorption properties. The groundnut
      shell based powdered activated carbon (GSPAC) has a higher surface area, iodine
      and methylene blue number compared to CPAC. Both of the carbons were used for the
      removal of malachite green dye from aqueous solution and the effect of various
      operating variables, viz. adsorbent dose (0.1-1 g l(-1)), contact time (5-120
      min) and adsorbate concentrations (100-200 mg l(-1)) on the removal of dye, has
      been studied. The experimental results indicate that at a dose of 0.5 g l(-1) and
      initial concentration of 100 mg l(-1), GSPAC showed 94.5% removal of the dye in
      30 min equilibrium time, while CPAC removed 96% of the dye in 15 min. The
      experimental isotherm data were analyzed using the linearized forms of
      Freundlich, Langmuir and BET equations to determine maximum adsorptive
      capacities. The equilibrium data fit well to the Freundlich isotherm, although
      the BET isotherm also showed higher correlation for both of the carbons. The
      results of comparative adsorption capacity of both carbons indicate that
      groundnut shell can be used as a low-cost alternative to commercial powdered
      activated carbon in aqueous solution for dye removal.

PMID- 17029776
TI  - Bioremediation of polycyclic aromatic hydrocarbons (PAHs)-contaminated sewage
      sludge by different composting processes.
AB  - The efficiency of four different composting processes to bioremediate polycyclic
      aromatic hydrocarbons (PAHs)-contaminated sewage sludge was investigated. Prior
      to composting, sewage sludge coming from the Datansha wastewater treatment plant,
      Guangzhou, China, was mixed with rice straw to obtain a C/N ratio of 13:1. After
      56 days of composting, the total concentrations of 16 PAHs (Sigma(PAHs)) ranged
      from 1.8 to 10.2 mg kg(-1) dry weight, decreasing in order of inoculated-manual
      turned compost (IMTC)>manual turned compost (MTC)>continuous aerated compost
      (CAC)>intermittent aerated compost (IAC), exhibiting removal rates of 64%, 70%,
      85% and 94%, respectively. Individual PAHs were generally removed in similar
      rates. IAC treatment showed a higher removal rate of high molecular weight PAHs
      and carcinogenic PAHs comparing to the other composting processes.

PMID- 17029777
TI  - Dehydrogenase based reagentless biosensor for monitoring phenylketonuria.
AB  - Phenylketonuria (PKU) is a disease characterized by an inability to metabolize
      the amino acid l-phenylalanine. The resulting buildup leads to brain damage and
      ultimately mental retardation in children if their phenylalanine intake is not
      carefully controlled. The National Institutes of Health recently suggested that
      people with PKU monitor their phenylalanine levels throughout their life and be
      put on a low phenylalanine diet. As an alternative approach to analysis using
      blood, this paper describes the first reagentless dehydrogenase based sensor for
      the determination of phenylalanine in human urine. The clinical range of
      phenylalanine in human urine is 20-60mM for people with PKU. Although most
      clinical analysis is performed using blood, urine was chosen due to its high
      concentrations of phenylalanine in phenylketonurics, as well as its simple, safe,
      and painless collection. The sensor is comprised of a carbon paste electrode with
      nicotinamide adenine dinucleotide (NAD(+)), phenylalanine dehydrogenase (PDH),
      uricase, and an electron mediator, 3,4-dihydroxybenzaldehyde (3,4-DHB), all mixed
      into the paste. The electron mediator reacts with the electrode surface to
      produce two redox species, which catalytically oxidize NADH. The behavior of the
      electron mediator mixed into a carbon paste electrode has not been previously
      investigated. Cyclic voltammetry was used to characterize the sensor's response
      to NADH, and with the addition of PDH and NAD(+) to the paste, its response to
      phenylalanine in human urine. The limit of detection for phenylalanine is 0.5mM
      (S/N=3).

PMID- 17029778
TI  - Electrochemical studies on horseradish peroxidase covalently coupled with redox
      dyes.
AB  - The present study aims at investigating the use of redox dyes as non-diffusional
      electron mediators in hydrogen peroxide biosensors using horseradish peroxidase
      (HRP). We observe that the two redox dyes Safranine O and Neutral Red covalently
      bound to HRP, efficiently mediate electron transfer from the active site of the
      enzyme to the electrode surface. Dyes bound to the enzyme using a spacer arm
      diaminohexane further enhance the electron transfer. The enzyme electrodes show a
      linear response to the concentration of H2O2 up to 500 microM concentration and
      with a detection limit of around 50 microM. The dyes can be used as coupled
      mediators to develop a successful electro-optical biosensor.

PMID- 17029779
TI  - Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes,
      using a flow immunoassay system.
AB  - An on-chip electrochemical flow immunoassay system for the detection of
      hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled
      with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity
      chromatography. An on-chip column packed with boronate-activated agarose beads
      was used for the separation of HbA1c from both non-glycated Hb and free antibody.
      Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical
      detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and
      HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical
      detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were
      injected onto a boronate-affinity column. HbA1c-antibody complexes were then
      trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently,
      elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes
      and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal
      was an estimation of the HbA1c amount. A linear correlation between the increase
      of current and HbA1c concentration was obtained up to an HbA1c concentration of
      500 microg/ml. The HbA1c flow immunoassay was successfully achieved using
      hemolysates. This electrochemical flow immunoassay system enabled us to construct
      a novel point-of-care testing device for the monitoring of glycated proteins
      including HbA1c.

PMID- 17029780
TI  - Immunomagnetic separation and MS/SPR end-detection combined procedure for rapid
      detection of Staphylococcus aureus and protein A.
AB  - The aim of this study was to establish an IMS-MS/SPR technique for the detection
      of Staphylococcus aureus (S. aureus) and Staphylococcus protein A (SPA) at the
      same time, which consists of isolating S. aureus and trapping-enrichmenting its
      SPA by IMS, and the end point is determined by using either MS or SPR
      measurements. Magnetic bead (MB) containing aldehyde group was synthesized with
      latex-polymerization and immunomagnetic bead (IMB) was fabricated by modifying
      its surface with an oriented layer of human IgG in covalent linkage. As soon as
      sample of pulverator-treated bacterial cell lysate (10(8) cfu/mL) was incubated
      with IMB at 4 degrees C for 30 min, SPA was captured and separated from the mixed
      solution in a few minutes by the IMB and then detected with mass spectrometry
      after washing. SPR was used to detect S. aureus quantitatively in situ at the end
      detection procedure. All in all, this technique can be employed to detect rapidly
      SPA and S. aureus within 2h and also be applied to detect other cells or their
      membrane proteins with changed modified antibodies.

PMID- 17029781
TI  - Reagentless biosensor for hydrogen peroxide based on immobilization of protein in
      zirconia nanoparticles enhanced grafted collagen matrix.
AB  - A novel matrix, zirconia nanoparticles enhanced grafted collagen (ZrO2-grafted
      collagen) hybrid composite, for immobilization of protein and biosensing was
      developed. The scanning electron microscopy, UV-vis and Fourier transform
      infrared spectra, and electrochemical measurements showed that the matrix was
      well biocompatible and could retain the bioactivity of immobilized protein to a
      large extent. The direct electron transfer of the immobilized myoglobin (Mb)
      exhibited a couple of stable and well-defined redox peaks with the formal
      potential of -336 mV (versus SCE) in 0.1M pH 7.0 PBS. This matrix could
      accelerate the electron transfer between Mb and the electrode with a surface
      controlled process and an electron transfer rate constant of 3.58+/-0.35s-1 at 10
      500 mVs-1. The Mb immobilized in the matrix showed a high thermal stability up to
      70 degrees C and an electrocatalytic activity to the reduction of hydrogen
      peroxide (H2O2) without the help of an electron mediator. The linear response
      range of the biosensor to H2O2 concentration was from 1.0 to 85.0 microM with the
      limit of detection of 0.63 microM at a signal-to-noise ratio of 3sigma. The
      biosensor exhibited high sensitivity, acceptable stability and reproducibility.
      This work opened a way for the further study on the direct electron transfer and
      biosensing application of the immobilized protein in collagen-related matrices.

PMID- 17029782
TI  - Ischemic preconditioning-induced activation of ERK1/2 in the rat hippocampus.
AB  - We investigated the activation and cellular localization of the extracellular
      signal-regulated kinases ERK1/2 in a rat model of ischemic tolerance induction.
      Adult male Sprague-Dawley rats were subjected to 3 min of sublethal ischemic
      preconditioning. Activation of ERK1/2 showed the characteristic time- and cell
      dependent patterns. Rapid and short-lasting activation of ERK after 3 min of
      cerebral ischemia was noted immediately in the dentate granule cells and mossy
      fibers of the hippocampus, and then occurred sequentially in CA3 and CA1 neurons
      and dentate hilar neurons at 10 min. Phosphorylation of ERK1/2 in hippocampal
      neurons returned to the basal level in an ordered manner. Basal level
      phosphorylation was attained first, at 30 min, by the CA1 neurons, and was then
      observed in CA3 and granule cells by 1 h and noted in some dentate hilar neurons
      at 12 h. By contrast, phosphorylation of ERK1/2 in mossy fibers and the CA1
      dendritic field was sustained for at least 3 d. Transient activation of ERK1/2
      was induced also in astrocytes of the dentate hilar region at 1 d post
      stimulation. These data demonstrate that the short cerebral-ischemic
      preconditioning induced rapid and transient activation of ERK1/2 in tolerance
      acquired CA1 neurons as well as in ischemia-resistant CA3 and dentate granule
      cells, and that the short preconditioning sustained activation in mossy fibers
      and neuropil areas, suggesting that ERK1/2 activation may be involved in the
      mechanism of ischemic tolerance in the rat hippocampus.

PMID- 17029783
TI  - COMT genotype, gender and cognition in community-dwelling, older adults.
AB  - A common polymorphism (Val158Met) in the gene encoding for the catechol-O
      methyltransferase (COMT) enzyme has been associated with differences in
      prefrontal cognitive function in schizophrenic patients and healthy adults. While
      several studies indicate that the Met allele is associated with better
      performance on measures of executive function, working memory and verbal fluency,
      results have been inconsistent. Furthermore, fewer studies have investigated this
      relationship in older adults, a group known to experience impairments in
      prefrontal cognitive functions. Additionally, findings vary according to the
      gender distribution of study participants. We examined whether COMT genotype
      interacted with gender to impact cognition in a cohort of 163 healthy, older
      adults. Memory, verbal ability and areas of prefrontal cognitive function,
      including attention, speed-of-processing, and executive function, were assessed.
      We found no significant association between COMT genotype and any cognitive
      measure. However, gender interacted with COMT genotype to impact cognitive
      performance. Males homozygous for the Val allele performed better than both the
      Val/Met and Met/Met groups on measures of delayed recall. Heterozygous women
      performed better than their homozygous counterparts on the measure of verbal
      ability. These findings suggest that gender may be an important variable in
      consideration of the impact of COMT on cognition. Further, when gender is taken
      into consideration, any negative impact of COMT genotype may extend to cognitive
      domains other than those associated with prefrontal regions.

PMID- 17029784
TI  - Transient cognitive deficits are associated with the reversible accumulation of
      amyloid precursor protein after mild traumatic brain injury.
AB  - Mild traumatic brain injury (MTBI) may frequently cause transient behavioral
      abnormalities without observable morphological findings. In this study, we
      investigated neuropathological mechanisms underlying transient cognitive deficits
      after MTBI. Mongolian gerbils were subjected to experimental MTBI. At various
      time points after injury, behavioral changes were evaluated by the open-field
      test and T-maze test, and immunohistochemistry of microtubule-associated protein
      (MAP2) and amyloid precursor protein (APP) was performed to examine disruptions
      of the neuronal cytoskeleton and axonal transport, respectively. Transient
      cognitive deficits were observed after MTBI. Sustained MAP2 loss was found within
      the cortical impact site, but not the hippocampus. Transient APP accumulation at
      the same time as transient cognitive deficits occurred in the ipsilateral
      hemisphere, particularly in the subcortical white matter. These results suggest
      that the axonal dysfunction indicated by the reversible APP accumulation in the
      white matter, but not the sustained neuronal cytoskeletal damage reflected by the
      cortical MAP2 loss confined to the impact site, is responsible for the transient
      functional deficits after MTBI.

PMID- 17029785
TI  - V180I mutation of the prion protein gene associated with atypical PrPSc
      glycosylation.
AB  - A valine to isoleucine mutation at residue 180 was identified in a French patient
      with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close
      vicinity of one of the two N-glycosylation sites of the cellular prion protein
      (PrP(C)). Western blot analysis revealed accumulation in the brain of the
      pathogenic proteinase K-resistant PrP (PrP(Sc)) isoform with the notable absence
      of the diglycosylated band. The mutant protein expressed in CHO cells was
      correctly glycosylated, suggesting that the atypical glycosylation pattern of
      PrP(Sc) was not due to the mutation at position 180. These results suggest that
      the diglycosylated form of the mutant PrP(180I) prevents its conversion into the
      pathogenic mutant form PrP(Sc180I), supporting a central role of N-linked glycan
      chains in the PrP conversion process.

PMID- 17029786
TI  - TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for
      research across Europe.
AB  - The regulatory regimes for research with residual tissue and accompanying data
      differ widely between countries in the European Union (EU): from specific consent
      to opt-out or even no consent at all. This could greatly hamper research where
      the exchange of tissue and accompanying data has become the gold standard, like
      in TubaFrost. Instead of adhering to international guidelines, which have a
      democratic deficit, or an attempt for a new set of possible harmonising rules,
      TubaFrost chose to create a coordinating rule: if tissue may legitimately be used
      for a certain kind of research in the country where it was taken and under whose
      jurisdiction the patient falls, it may also be used for such research in the
      country where it is sent to in the context of a scientific program even if in
      that other country other regulations would apply for research with residual
      tissue taken from patients under their jurisdiction. This coordinating rule has a
      sound basis in EU law in general and will solve the problems related to diverging
      national regulatory regimes in the case of cross national research with residual
      tissue.

PMID- 17029787
TI  - TuBaFrost 5: multifunctional central database application for a European tumor
      bank.
AB  - Developing a tissue bank database has become more than just logically arranging
      data in tables combined with a search engine. Current demand for high quality
      samples and data, and the ever-changing legal and ethical regulations mean that
      the application must reflect TuBaFrost rules and protocols for the collection,
      exchange and use of tissue. To ensure continuation and extension of the TuBaFrost
      European tissue bank, the custodianship of the samples, and hence the decision
      over whether to issue samples to requestors, remains with the local collecting
      centre. The database application described in this article has been developed to
      facilitate this open structure virtual tissue bank model serving a large group.
      It encompasses many key tasks, without the requirement for personnel, hence
      minimising operational costs. The Internet-accessible database application
      enables search, selection and request submission for requestors, whereas
      collectors can upload and edit their collection. Communication between requestor
      and involved collectors is started with automatically generated e-mails.

PMID- 17029788
TI  - Randomized controlled trial of exercise for chronic whiplash-associated
      disorders.
AB  - Whiplash-associated disorders are common and incur considerable expense in social
      and economic terms. There are no known effective treatments for those people
      whose pain and disability persist beyond 3 months. We conducted a randomized,
      assessor-blinded, controlled trial at two centres in Australia. All participants
      received 3 advice sessions. In addition the experimental group participated in 12
      exercise sessions over 6 weeks. Primary outcomes were pain intensity, pain
      bothersomeness and function measured at 6 weeks and 12 months. Exercise and
      advice was more effective than advice alone at 6 weeks for all primary outcomes
      but not at 12 months. The effect of exercise on the 0-10 pain intensity scale was
      -1.1 (95%CI -1.8 to -0.3, p=0.005) at 6 weeks and -0.2 (0.6 to -1.0, p=0.59) at
      12 months; on the bothersomeness scale the effect was -1.0 (-1.9 to -0.2,
      p=0.003) at 6 weeks and 0.3 (-0.6 to 1.3, p=0.48) at 12 months. The effect on
      function was 0.9 (0.3 to 1.6, p=0.006) at 6 weeks and 0.6 (-0.1 to 1.4, p=0.10)
      at 12 months. High levels of baseline pain intensity were associated with greater
      treatment effects at 6 weeks and high levels of baseline disability were
      associated with greater treatment effects at 12 months. In the short-term
      exercise and advice is slightly more effective than advice alone for people with
      persisting pain and disability following whiplash. Exercise is more effective for
      subjects with higher baseline pain and disability.

PMID- 17029789
TI  - Less calcemic Vitamin D analogs enhance creatine kinase specific activity and
      modulate responsiveness to gonadal steroids in the vasculature.
AB  - Vitamin D receptors are widely expressed in the cardiovascular system, in which
      Vitamin D and its metabolites exert a variety of biological activities such as
      regulation of cellular proliferation and differentiation, cell calcium transients
      and cell energy metabolism in vitro. The latter is mediated through the control
      of the brain type creatine kinase specific activity (CK), which serves to provide
      a readily available reservoir for ATP generation under increased work-load. In
      the present study we undertook to assess the role of Vitamin D on energy
      metabolism in the rat heart and aorta in vivo by using CK, which is a key energy
      metabolizing enzyme and compare Vitamin D depleted and repleted animals. Vascular
      tissues from female or male Vitamin D-depleted rats showed 61-80% lower CK
      activity in the aorta (Ao) and left ventricle of the heart (Lv) than control,
      Vitamin D-replete rats. Moreover, neither estradiol-17beta (E2) nor
      dihydrotestosterone (DHT), which increases CK specific activity in Ao and Lv of
      intact female or male rats, respectively, were able to stimulate CK in Vitamin D
      depleted rats. Treatment of intact female rats for 2 weeks or 2 months with the
      less-calcemic Vitamin D analogs JKF 1624F2-2 (JKF) or QW 1624F2-2 (QW) (Fig. 1),
      did not significantly affect CK specific activity. However, after pretreatment
      with these analogs, there was an up regulation of the E2-induced CK response in
      Ao and Lv. In intact female rats, all Vitamin D analogs also potentiated the in
      vivo CK response to the SERMs raloxifene (Ral) and tamoxifen (TAM) in Ao and Lv.
      However the inhibitory effect of Ral or TAM on E2-induced CK activity was lost
      after pretreatment with Vitamin D analogs. The non-calcemic analog CB 1093 (CB)
      induced a significant increase in estradiol receptor alpha (ERalpha) protein in
      both myocardial and aortic tissue from intact and from ovariectomized female
      rats. Collectively, these results indicate that Vitamin D analogs modulate cell
      energy homeostasis in vascular tissues through induction of CK and up regulation
      of the response and sensitivity of CK in vascular tissues to E2 and to SERMs,
      possibly through via an increase in ERalpha protein in female derived organs.
      These results corroborate our previous in vitro studies in human vascular cells
      and further suggest that the Vitamin D system plays an important physiological
      role in maintaining normal cell energy reservoir in the vasculature.

PMID- 17029790
TI  - Genotypic characterisation of Indian cattle, buffalo and sheep isolates of
      Echinococcus granulosus.
AB  - Twelve isolates of Echinococcus granulosus, collected from domestic animals,
      including cattle, buffalo and sheep were analysed for DNA nucleotide sequence
      variation within mitochondrial cytochrome c oxidase I (coxI), NADH dehydrogenase
      subunit I (nadI) and internal transcribed spacer gene I (ITS1). After analysis of
      sequence information this was found that the fragment size of ITS1 of buffalo
      isolate was more in comparison to cattle and sheep isolates. Based on the nadI
      genotype this was found that Indian cattle, buffalo and sheep isolates could be
      grouped into E. granulosus sensu stricto. Based on coxI genotype two sheep
      isolates and one buffalo isolate were homologous to G2 genotype. Rests of the
      isolates were microvariants of G2 genotype. Presence of G2 genotype in buffalo is
      the first report of this genotype from this host.

PMID- 17029791
TI  - Autohydrolysis of agricultural residues: study of reaction byproducts.
AB  - Samples of rice husks and corn cobs were subjected to hydrothermal treatments in
      aqueous media under conditions leading to maximal xylooligomer concentration, and
      the reaction liquors were extracted with dichloromethane (DCM) to assess the type
      and amount of reaction byproducts with potential application as food ingredients
      and cosmetics. The identified DCM-soluble compounds were classified in four
      categories (sugar-derived compounds, lignin-derived compounds, nitrogen
      containing compounds and fatty acids). The experimental results were compared
      with literature data.

PMID- 17029792
TI  - Preparation and characterization of activated carbon from rice bran.
AB  - A study on the preparation of rice bran-based activated carbon was conducted,
      with and without an acid treatment step prior the activation process. The
      influence of the activation time on the structure of the activated carbons was
      evaluated. The acid treatment had a significant positive influence on sorption
      properties. The rice bran-activated carbon presented a BET surface area of
      652m(2)g(-1) and a pore volume of 0.137cm(3)g(-1), with mesopores predominance
      (ca. 55%). These experimental results indicated the potential use of rice bran as
      a precursor in the activated carbon preparation process, thus representing an
      economically promising material.

PMID- 17029793
TI  - Purification and characterization of butyrate-induced protein phosphatase
      involved in apoptosis of Ehrlich ascites tumor cells.
AB  - Short chain fatty acids including butyrate exhibit wide variety of biological
      effects towards cell growth, morphology and gene expression. In this report, we
      study the mechanism by which butyrate (BuA) modulates the expression of protein
      phosphatase when treated to the cells. As a model system, we used Ehrlich Ascites
      Tumor (EAT) cells in which BuA-treatment induces expression of a protein
      phosphatase enzyme. Subsequently, BuA-induced protein phosphatase has been
      biochemically purified and characterized. Further, pretreatment of caspase-3
      inhibitor abolished the activity of BuA-induced protein phosphatase indicating
      the involvement of caspase-3 in the activation of BuA-induced protein
      phosphatase. In addition, the relationship between BuA-induced protein
      phosphatase and apoptosis has been verified. Activation of endonuclease-II has
      been shown in BuA-treated EAT cells and that activity was completely inhibited by
      sodium orthovanadate, a tyrosine phosphatase inhibitor suggesting that
      endonuclease-II may serve as a possible down-stream target for BuA-induced
      protein phosphatase. Together, the data suggest that activation of protein
      phosphatase may be an early and essential step in BuA-mediated apoptotic
      signaling pathway in EAT cells.

PMID- 17029794
TI  - On the simulation of enzymatic digest patterns: the fragmentation of oligomeric
      and polymeric galacturonides by endo-polygalacturonase II.
AB  - A simulation methodology for predicting the time-course of enzymatic digestions
      is described. The model is based solely on the enzyme's subsite architecture and
      concomitant binding energies. This allows subsite binding energies to be used to
      predict the evolution of the relative amounts of different products during the
      digestion of arbitrary mixtures of oligomeric or polymeric substrates. The
      methodology has been specifically demonstrated by studying the fragmentation of a
      population of oligogalacturonides of varying degrees of polymerization, when
      digested by endo-polygalacturonase II (endo-PG II) from Aspergillus niger.

PMID- 17029795
TI  - Pyrroloquinoline quinone nutritional status alters lysine metabolism and
      modulates mitochondrial DNA content in the mouse and rat.
AB  - Pyrroloquinoline quinone (PQQ) added to purified diets devoid of PQQ improves
      indices of perinatal development in rats and mice. Herein, PQQ nutritional status
      and lysine metabolism are described, prompted by a report that PQQ functions as a
      vitamin-like enzymatic cofactor important in lysine metabolism (Nature 422 [2003]
      832). Alternatively, we propose that PQQ influences lysine metabolism, but by
      mechanisms that more likely involve changes in mitochondrial content. PQQ
      deprivation in both rats and mice resulted in a decrease in mitochondrial
      content. In rats, alpha-aminoadipic acid (alphaAA), which is derived from alpha
      aminoadipic semialdehyde (alphaAAS) and made from lysine in mitochondria, and the
      plasma levels of amino acids known to be oxidized in mitochondria (e.g., Thr,
      Ser, and Gly) were correlated with changes in the liver mitochondrial content of
      PQQ-deprived rats, but not PQQ-supplemented rats. In contrast, the levels of NAD
      dependent alpha-aminoadipate-delta-semialdehyde dehydrogenase (AASDH), a
      cytosolic enzyme important to alphaAA production from alphaAAS, was not
      influenced by PQQ dietary status. Moreover, the levels of U26 mRNA were not
      significantly changed even when diets differed markedly in PQQ and dietary lysine
      content. U26 mRNA levels were measured, because of U26's proposed, albeit
      questionable role as a PQQ-dependent enzyme involved in alphaAA formation.

PMID- 17029796
TI  - C-phycocyanin transcriptionally regulates uPA mRNA through cAMP mediated PKA
      pathway in human fibroblast WI-38 cells.
AB  - We have previously demonstrated the efficacy of c-phycocyanin in up-regulation of
      urokinase-type plasminogen activator (uPA) in bovine endothelial cell line.
      However, the mechanism of action and pathway elucidation in uPA regulation is
      unclear. In experiments reported here, we have investigated the mechanism of
      action of c-phycocyanin (c-pc) induced uPA gene modulation in human fibroblast
      (WI-38) cell line. ELISA test confirmed that c-pc increased the uPA antigen
      whereas PAI-1 antigen level was unaffected. Treatment of cells with c-pc
      significantly (P<0.05) enhanced the uPA mRNA level in a dose (50 microg/ml) and
      time dependent (up to 4 h) manner. This effect of c-pc was abolished by treatment
      with dichloro-1-beta-D-ribofuranosyl benzamidazole (DRB) (10 microg/ml). Co
      treatment of c-pc with 200 microg/ml cycloheximide (CHX), translation inhibitor,
      resulted in over accumulation of uPA mRNA. These results suggest that uPA
      induction by c-pc is transcriptionally regulated and does not require de novo
      protein synthesis. We also provide evidence that c-pc stimulates uPA gene through
      cAMP dependent pathway as adenylyl cyclase (AC) inhibitor, dideoxyadenosine (DDA)
      significantly inhibited the uPA mRNA expression and co-treatment with adenylyl
      cyclase analogue, dBcAMP recovered the effect of c-pc on gene activity.
      Furthermore, the present investigation provides evidence on the regulatory
      pathway involved in the c-pc stimulus. C-pc induced uPA expression was completely
      inhibited by PKA inhibitor (KT 5200), indicating the regulation is dependent on
      PKA pathway. Elimination of PKC pathway components by prolonged incubation with
      excess amount of phorbol 12-myristate 13-acetate (PMA) failed to abolish the c-pc
      effect on uPA expression indicating the regulation is independent of PKC pathway.
      Taken together, our data indicate that uPA gene regulation by c-pc is
      transcriptionally controlled through cAMP mediated PKA pathway.

PMID- 17029797
TI  - Synthesis and anti-microbial activity of pyrazolylbisindoles--promising anti
      fungal compounds.
AB  - A series of pyrazolylbisindole derivatives have been synthesized by reacting
      substituted pyrazole aldehydes with substituted indoles using phosphotungstic
      acid, a Keggin type heteropoly acid as catalyst. The synthesized
      pyrazolylbisindoles were evaluated for anti-microbial activities. The effect of
      pyrazolylbisindoles on the mycelial growth of plant pathogenic fungi is revealed.
      Entries 3c and 3d emerged as the most interesting compounds in this series
      exhibiting excellent anti-fungal activity.

PMID- 17029798
TI  - Prenatal development of hypothalamic neuropeptide systems in the nonhuman
      primate.
AB  - In the rodent, arcuate nucleus of the hypothalamus (ARH)-derived neuropeptide Y
      (NPY) and proopiomelanocortin (POMC) neurons have efferent projections throughout
      the hypothalamus that do not fully mature until the second and third postnatal
      weeks. Since this process is likely completed by birth in primates we
      characterized the ontogeny of NPY and melanocortin systems in the fetal Japanese
      macaque during the late second (G100), early third (G130) and late third
      trimesters (G170). NPY mRNA was expressed in the ARH, paraventricular nucleus
      (PVH), and dorsomedial nucleus of the hypothalamus (DMH) as early as G100. ARH
      derived NPY projections to the PVH were initiated at G100 but were limited and
      variable; however, there was a modest increase in density and number by G130. ARH
      NPY/agouti-related peptide (AgRP) fiber projections to efferent target sites were
      completely developed by G170, but the density continued to increase in the
      postnatal period. In contrast to NPY/AgRP projections, alphaMSH fibers were
      minimal at G100 and G130 but were moderate at G170. This study also revealed
      several significant species differences between rodent and the nonhuman primate
      (NHP). There were few NPY/catecholamine projections to the PVH and ARH prior to
      birth, while projections were increased in the adult. A substantial proportion of
      the catecholamine fibers did not coexpress NPY. In addition, cocaine and
      amphetamine-related transcript (CART) and alpha-melanocyte stimulating hormone
      (alphaMSH) were not colocalized in fibers or cell bodies. As a consequence of the
      prenatal development of these neuropeptide systems in the NHP, the maternal
      environment may critically influence these circuits. Additionally, because
      differences exist in the neuroanatomy of NPY and melanocortin circuitry the
      regulation of these systems may be different in primates than in rodents.

PMID- 17029799
TI  - 5-HT activates vagal afferent cell bodies in vivo: role of 5-HT2 and 5-HT3
      receptors.
AB  - Occipital artery (OA) injections of 5-HT elicit pronounced reductions in heart
      rate and mean arterial blood pressure (MAP) in urethane-anesthetized rats by
      activation of vagal afferent cell bodies in the ipsilateral nodose ganglion. In
      contrast, internal carotid artery (ICA) and i.v. injections elicit similar
      cardiovascular responses by activation of peripheral vagal afferent terminals.
      The aim of this study was to examine the roles of 5-HT3 and 5-HT2 receptors in
      the 5-HT-induced activation of vagal afferent cell bodies and peripheral afferent
      terminals in urethane-anesthetized rats. OA, ICA and i.v. injections of 5-HT
      elicited dose-dependent reductions in heart rate and MAP that were virtually
      abolished after i.v. administration of the 5-HT3 receptor antagonists, MDL 7222
      or ICS 205-930. The responses elicited by the OA injections of 5-HT were markedly
      diminished after i.v. injection of the 5-HT2 receptor antagonists, xylamidine or
      ketanserin, whereas the responses elicited by i.v. or ICA injections of 5-HT were
      not affected. The present findings suggest that (1) 5-HT3 and 5-HT2 receptor
      antagonists gain ready access to nodose ganglion cells upon i.v. administration,
      and (2) functional 5-HT3 and 5-HT2 receptors exist on the cell bodies of vagal
      afferent neurons mediating the cardiovascular responses elicited by OA injections
      of 5-HT. These findings also support a wealth of evidence that 5-HT3 receptors
      exist on the peripheral terminals of vagal afferents, and although they do not
      discount the possibility that 5-HT2 receptors exist on peripheral vagal afferent
      terminals, it appears that activation of these receptors does not have pronounced
      effects on 5-HT3 receptor activity on terminals that mediate the hemodynamic
      responses to 5-HT.

PMID- 17029800
TI  - Dopamine innervation of the monkey mediodorsal thalamus: Location of projection
      neurons and ultrastructural characteristics of axon terminals.
AB  - Dopamine (DA) axons and receptors have recently been identified in the primate
      thalamus, including the mediodorsal thalamic nucleus (MD). In order to determine
      whether the DA innervation of the primate MD shares the anatomical features of
      the mesocortical or nigrostriatal DA projections, we performed tract-tracing and
      immunocytochemistry studies in macaque monkeys (Macaca fascicularis) to identify
      the location of the DA neurons that project to MD and immuno-electron microscopy
      to determine the distribution of the dopamine transporter (DAT) in axons within
      the MD. Similar to the mesocortical projection, retrogradely-labeled, tyrosine
      hydroxylase-containing neurons were present in dorsal tier ventral mesencephalic
      nuclei, such as the ventral tegmental area and the dorsal portion of the
      substantia nigra pars compacta. In contrast, no dual-labeled neurons were present
      in the ventral tier nuclei, the primary origin of the nigrostriatal DA pathway.
      In addition, like the DA projection to the prefrontal cortex, DAT
      immunoreactivity was predominantly localized to the pre-terminal portion of axons
      in the MD, and was infrequently found in association with synaptic vesicles, in
      contrast to nigrostriatal DA axons. These findings indicate that the DA
      projection to the MD shares anatomical features with the mesocortical DA system,
      suggesting that the functional properties of DA neurotransmission in the MD might
      be more similar to those in the cortex than in the striatum.

PMID- 17029801
TI  - Occipital artery injections of 5-HT may directly activate the cell bodies of
      vagal and glossopharyngeal afferent cell bodies in the rat.
AB  - The primary objective of this study was to determine whether circulating factors
      gain direct access to and affect the activity of vagal afferent cell bodies in
      the nodose ganglia and glossopharyngeal afferents cell bodies in the petrosal
      ganglia, of the rat. We found that the occipital and internal carotid arteries
      provided the sole blood supply to the nodose ganglia, and that i.v. injections of
      the tracer, Basic Blue 9, elicited strong cytoplasmic staining in vagal and
      glossopharyngeal afferent cell bodies that was prevented by prior ligation of the
      occipital but not the internal carotid arteries. We also found that occipital
      artery injections of 5-HT elicited pronounced dose-dependent reductions in heart
      rate and diastolic arterial blood pressure that were (1) virtually abolished
      after application of the local anesthetic, procaine, to the ipsilateral nodose
      and petrosal ganglia, (2) markedly attenuated after transection of the
      ipsilateral vagus between the nodose ganglion and brain and virtually abolished
      after subsequent transection of the ipsilateral glossopharyngeal nerve between
      the petrosal ganglion and the brain, (3) augmented after ipsilateral transection
      of the aortic depressor and carotid sinus nerves, and (4) augmented after
      transection of all ipsilateral glossopharyngeal and vagal afferent nerves except
      for vagal cardiopulmonary afferents. These findings suggest that blood-borne 5-HT
      in the occipital artery gains direct access to and activates the cell bodies of
      vagal cardiopulmonary afferents of the rat and glossopharyngeal afferents of
      undetermined modalities.

PMID- 17029802
TI  - Dysphagic phagocytosis by thyroid epithelium.

PMID- 17029803
TI  - The risk factor association syndrome as a barisystemic syndrome: a view on
      obesity and the metabolic syndrome.
AB  - A number of factors are known to be associated to an increased risk of
      cardiovascular disease. High blood pressure, lipid abnormalities, type 2 diabetes
      mellitus, obesity and sleep apnea may act as isolated risk factors but,
      frequently, coexist in the same person. Studies involving surgery aimed at weight
      reduction (bariatric surgery - from barys, the greek term for heavy) have
      consistently shown a high probability of resolution of major risk factors, namely
      of diabetes, hyperlipidemia and hypertension, associated to weight reduction.
      Data in a similar direction were obtained after weight reduction was reached by
      means of pharmacological therapy. Excessive weight thus may stand as the probable
      cause for a number of cardiovascular risk factors, at least in many patients with
      an adequate genetic background. The moment may have come to focus on causality
      and to suggest that the risk factor association syndrome, in patients with
      overweight/obesity, may be defined as the systemic consequences of excessive
      weight, including hormonal, body habitus, metabolic, hemodynamic and respiratory
      parameters. A suitable name for the syndrome might be the barisystemic syndrome.

PMID- 17029804
TI  - Electroatriography - time-frequency analysis of atrial fibrillation from modified
      12-lead ECG configurations for improved diagnosis and therapy.
AB  - Current atrial fibrillation (AF) management guidelines suggest that initially a
      decision must be made to apply either a rate control or rhythm control strategy
      in the individual patient. However, patients' selection remains substantially
      empirical and the strategy initially chosen often proves unsuccessful and
      alternative therapies must be adopted. Thus, it seems desirable to develop and
      apply tests that quantify AF disease state and guide AF management. The overall
      hypothesis of this paper is that time-frequency analysis of AF from modified 12
      lead ECG configurations will improve AF management beyond current diagnostic and
      therapeutic standards. In particular, we present a novel concept in which 12-lead
      ECG configurations are modified for time-frequency analysis of AF
      (electroatriography). While five electrodes (VR, VL, VF, V1, V2) are placed in
      the conventional position, the other four electrodes (V3, V4, V5, V6) are
      empirically repositioned anterior or posterior over the atria. By applying
      spatiotemporal QRST cancellation and time-frequency analysis to these recordings
      in 19 patients with persistent AF, fibrillatory rate dispersion among individual
      anterior (25+/-14 fibrillations per minute, fpm) and posterior leads (16+/-11fpm)
      as well as individual anterior/posterior rate gradients ranging between -24 and
      +116fpm could be identified. Consequently, the portrayed techniques may form the
      conceptual basis for individualized noninvasive characterization of AF.
      Initiation of further studies using the described techniques in different AF
      subsets, for comparisons with intracardiac recordings and outcome of different
      therapies, e.g. cardioversion, antiarrhythmic drug and ablation therapy may be
      stimulated.

PMID- 17029805
TI  - Chemisorption of proteins and their thiol derivatives onto gold surfaces:
      characterization based on electrochemical nonlinearity.
AB  - This study was conducted to monitor the electrochemical responses of two proteins
      (bovine serum albumin (BSA) and gelatin) and their thiol derivatives adsorbed
      onto gold (Au) electrodes, which were analyzed by a "nonlinear" impedance method.
      A sinusoidal voltage is applied to a protein-containing aqueous solution and the
      waveform of the output current is analyzed by fast Fourier transformation (FFT).
      The intensities of the higher harmonics in the FFT varied with the species of
      protein and their thiol derivatives, and with time. From the higher harmonics,
      voltage-dependent capacitance and conductance were quantitatively evaluated to
      differentiate the state of adsorbed protein. Adsorption and desorption
      characteristics of BSA and its thiol derivative on the Au surface were
      continuously measured by a quartz crystal microbalance (QCM) in situ. The
      microscopic state of thiol-derivatized BSA adsorbed onto the Au surface was
      imaged by atomic force microscopy (AFM). In general, thiol-derivatized proteins
      were tightly adsorbed on the Au surface and showed no desorption. The present
      electrochemical measurements clearly differentiated adsorption characteristics of
      physically adsorbed (physisorbed) and chemically adsorbed (chemisorbed) proteins
      on Au surfaces.

PMID- 17029806
TI  - Theoretical basis for differential scanning calorimetric analysis of multimeric
      proteins.
AB  - A new general equation simulating irreversible DSC transitions of multimeric
      proteins was developed. The equation put forward here is the result of an
      improved mathematical re-elaboration of the classical Lumry-Eyring models, where
      no restrictive a priori assumptions are made on the kinetic constraints of the
      denaturation process, or on the enthalpy of the final denatured state. In order
      to test the wide applicability of this new effective theoretical tool, a series
      of DSC transitions were simulated with the aim of determining the effects of all
      relevant thermodynamic, kinetic or experimental parameters on the shape of DSC
      profiles. Moreover, the classical equations used widely in DSC investigations for
      the calculus in both kinetic parameters and changes of molecularity, were studied
      in the light of the model developed here, highlighting, in each case, their
      rather limited applicability. The new approach proposed in this article was
      applied to study the thermal denaturation of an hexameric protein (Glucosamine-6
      phosphate deaminase), putting in evidence the practical applicability of the
      theoretical equations developed.

PMID- 17029807
TI  - Thermodynamics of sequence-specific protein-DNA interactions.
AB  - The molecular recognition processes in sequence-specific protein-DNA interactions
      are complex. The only feature common to all sequence-specific protein-DNA
      structures is a large interaction interface, which displays a high degree of
      complementarity in terms of shape, polarity and electrostatics. Many molecular
      mechanisms act in concert to form the specific interface. These include
      conformational changes in DNA and protein, dehydration of surfaces,
      reorganization of ion atmospheres, and changes in dynamics. Here we review the
      current understanding of how different mechanisms contribute to the
      thermodynamics of the binding equilibrium and the stabilizing effect of the
      different types of noncovalent interactions found in protein-DNA complexes. The
      relation to the thermodynamics of small molecule-DNA binding and protein folding
      is also briefly discussed.

PMID- 17029808
TI  - Comparison between breast volume measurement using 3D surface imaging and
      classical techniques.
AB  - Quantification of the complex breast region can be helpful in breast surgery,
      which is shaped by subjective influences. However, there is no generally
      recognized method for breast volume calculation. Three-dimensional (3D) body
      surface imaging represents a new alternative for breast volume computation. The
      aim of this work was to compare breast volume calculation with 3D scanning and
      three classic methods, focusing on relative advantages, disadvantages, and
      reproducibility. Repeated breast volume calculations of both breasts in six
      patients (n=12) were performed using a 3D laser scanner, nuclear magnetic
      resonance imaging (MRI), thermoplastic castings, and anthropomorphic
      measurements. Mean volumes (cc) and mean measurement deviations were calculated,
      and regression analyses were performed. MRI showed the highest measurement
      precision, with a mean deviation (expressed as a percentage of mean breast
      volume) of 1.56+/-0.52% compared with 2.27+/-0.99% for the 3D scanner, 7.97+/
      3.53% for thermoplastic castings, and 6.26+/-1.56% for the anthropomorphic
      measurements. Breast volume calculations using MRI showed the best agreement with
      3D scanning measurement (r=0.990), followed by anthropomorphic measurement
      (r=0.947), and thermoplastic castings (r=0.727). Compared with three classical
      methods of breast volume calculation, 3D scanning provides acceptable accuracy
      for breast volume measurements, better spatial interpretation of the anatomical
      area to be operated on (due to lack of chest deformation), non-invasiveness, and
      good patient tolerance. After this preliminary study and further development, we
      believe that 3D body surface scanning could provide better preoperative planning
      and postoperative control in everyday clinical practice.

PMID- 17029809
TI  - Expression of the GLUT1 glucose transporter, p63 and p53 in thyroid carcinomas.
AB  - Only few studies have evaluated the usefulness of the GLUT1 and p63 status of
      thyroid carcinomas in revealing tumorigenesis. We studied GLUT1, p53, and p63
      immunoexpression in a total of 86 cases of various thyroid carcinoma types to
      determine the biological significance of GLUT1 and p63 expression in thyroid
      carcinomas. GLUT1 was detected in six cases of anaplastic carcinoma and in one
      case of poorly differentiated carcinoma with membranous staining. p63 was
      detected in five cases of anaplastic carcinoma, in one case of poorly
      differentiated carcinoma, and in five cases of papillary carcinoma with nuclear
      positivity. p53 was detected in six cases of anaplastic carcinoma, in one case of
      poorly differentiated carcinoma, and in one case of follicular carcinoma with
      nuclear positivity. Five of seven cases of anaplastic carcinoma expressed all
      three of these markers. The results suggest that GLUT1, p63, and p53 are not
      expressed in well-differentiated thyroid carcinomas, and that they are usually
      expressed late in the course of thyroid tumor progression. These data strongly
      suggest that in anaplastic carcinomas, impairment of p53-mediated repression
      results in increased GLUT1 and p63 expression, and that this probably reflects
      the differential regulation of hypoxia-responsive pathways and basal/stem cell
      regulatory pathways.

PMID- 17029810
TI  - Standard free energies of binding of solute to proteins in aqueous medium. Part
      1: Thermodynamic analysis for multicomponent system.
AB  - Using an equilibrium dialysis technique, moles (Gamma(2)(1)) of cationic and
      anionic surfactants bound per kilogram of proteins of various types in aqueous
      media have been measured previously in this laboratory under different
      physicochemical conditions. From a thermodynamic analysis in the present paper,
      Gamma(2)(1) has been shown to be equal to the Gibbs relative excess of surfactant
      per kilogram of protein at a measured value of solute activity, a(2). The values
      of relative solvent excesses, Gamma(2)(1) (which are negative for surfactants)
      can be estimated from values of Gamma(2)(1) and a(2). Using the Gibbs-Duhem
      relationship for protein solution inside the dialysis bag and dialysate solutions
      respectively at equilibrium, an integrated expression for the standard free
      energy change, DeltaG(o) (in kilojoules per kilogram of protein for binding with
      ligand as a result of the change of a(2) from zero to unity) can be calculated
      from experimental data. The isopiestic vapour pressure technique was used
      extensively for evaluation of negative binding (-Gamma(2)(1)) of inorganic salts
      to proteins of different types for various values of a(2) of salts present in the
      bulk media. With some modifications of our derived equations for free energy of
      binding in such a system, DeltaG(o) has been evaluated for the change of mean
      activity of electrolyte from zero to unity in the rational scale. DeltaG(o) is
      positive since Gamma(2)(1) is negative and Gamma(2)(1) is positive for such ionic
      systems. DeltaG(o) in all cases, however, are expressed in terms of the standard
      state of reference of unit activity so that their magnitudes and sign can be
      related to the relative affinities of a solute for binding with proteins in
      aqueous media.

PMID- 17029811
TI  - Fourier analysis of potential oscillations of a liquid membrane for the
      discrimination of taste substances.
AB  - Electrical potential oscillations were obtained across a liquid membrane composed
      of nitrobenzene/picric acid placed between two aqueous phases in the presence of
      various taste (i.e. salty, sweet and bitter) substances. The influence of these
      compounds on electrical oscillations was studied using Fourier analysis to
      establish a "fingerprint" of the substance that can be correlated with its taste
      index. Various concentrations of each substance were tested to obtain a Fourier
      spectrum with discrete peaks which can be further processed. The electrical
      oscillations consisted of a number of weak damped oscillators, and the Fourier
      spectra of these signals were found to have a number of discrete peaks of
      decreasing amplitude at low frequencies (0-0.5 Hz). A correlation of the
      frequency of the first peak of the Fourier spectrum with the taste index was
      found for bitter substances, whereas for salty substances the amplitude of the
      first two peaks of the spectrum was correlated with the taste index.

PMID- 17029812
TI  - Store-operated Ca2+ entry: A STIMulating stOrai.
AB  - Store-operated Ca2+ entry (SOCE) mediates much of the Ca2+ entry evoked by
      receptors that stimulate phospholipase C. However, for 20 years, the plasma
      membrane Ca2+ channel and the signal linking its activation to loss of Ca2+ from
      the endoplasmic reticulum (ER) have eluded detection. But the search might now be
      over. Two proteins, STIM1 (the ER Ca2+ sensor) and Orai1 (the Ca2+ channel), have
      recently been identified as the missing links in SOCE.

PMID- 17029813
TI  - Argonaute: A scaffold for the function of short regulatory RNAs.
AB  - Argonaute is the central protein component of RNA-silencing mechanisms. It
      provides the platform for target-mRNA recognition by short regulatory guide RNA
      strands and the Slicer catalytic activity for mRNA cleavage in RNA interference.
      Multiple Argonaute sub-families can be identified phylogenetically yet, despite
      this diversity, molecular and sequence analyses show that Argonaute proteins
      share common molecular properties and the capacity to function through a common
      mechanism. Recently, the members of the Piwi sub-family have been shown to
      interact with new classes of short regulatory RNAs, Piwi-interacting RNAs
      (piRNAs) and repeat-associated small interfering RNAs (rasiRNAs), which has
      implications for developmental processes and introduces a new dimension to the
      field of RNA silencing.

PMID- 17029814
TI  - [Epidemiology of candidemia: results of a one month French hospitals-based
      surveillance study in 2004].
AB  - INTRODUCTION: The aim of our study was to determinate the frequency of
      candidemia, the species encountered and their susceptibility to antifungal agents
      in French hospitals in 2004. METHODS: A prospective survey of septicaemia,
      including candidaemia was conducted among 193 non teaching French hospitals
      during October 2004. All bloodstream infections were reported and the bloodstream
      isolates sent to two coordinating centers. Species identification and
      susceptibility were performed by biologists as usual, and further confirmed by
      use of alternative methods, including Minimal Inhibitory Concentration (MIC)
      determination. RESULTS: The survey was effective in 93 hospitals, where 2013
      bloodstream infections were noticed, including 46 candidaemia (2.3%). Candida sp.
      Is the 7th pathogen responsible for bloodstream infection, without concern of the
      origin of the infection. Candidaemia was hospital acquired in 80.4% of cases
      (N=37/46). Candidaemia represents 0.7% (N=9/1211) of community-acquired
      bloodstream infections but 4.5% (N=37/802) of nosocomial cases, placing Candida
      sp. at the 5th row of frequency in this last group. No mistakes were noticed
      during identification, but two strains were not named. After confirmation of
      identification, species are distributed as follows: 23 C.albicans (50%), 13
      C.glabrata (28.3%), 5 C.tropicalis (10.9%), 3 C.parapsilosis (6.5%), 1 C.krusei
      (2.2%), and 1 C.kefyr (2.2%). The overall susceptibility is 97.7% for
      amphotericin B, 93.2% for 5-fluorocytosin, 88.6% for fluconazole, 70.5% for
      itraconazole, 95.5% for voriconzole and 100% of strains had very low MIC for
      caspofungin. Concerning the two main species isolated, 95.5% of C.albicans
      strains remain susceptible to fluconazole, but only 69% of C.glabrata strains.
      Two strains, 1 C.albicans and 1 C.glabrata exhibit cross resistance to azoles.
      The majority of amphotericin, fluconazole, and itraconazole decreased
      susceptibility strains are found into C.glabrata strains, but susceptibility to 5
      fluorocytosin and very low MCI to caspofungin remained in this species.
      CONCLUSION: Our survey allowed us to get data from French non-teaching hospitals
      in 2004 about frequency of candidaemia among septicaemia. Candida species
      distribution and in vitro susceptibility patterns of the strains isolated.
      Candidaemia is not a rare event, specially when septicaemia is nosocomially
      acquired. C.albicans is the main species isolated and remains highly in vitro
      susceptible to antifungals. One important feature is the frequency of C.glabrata
      in our survey. Considering its decreased susceptibility to azoles, this finding
      confirms the need for rapid identification of yeast isolated from bloodstream
      samples, and antifungal susceptibility testing each time it is available.

PMID- 17029816
TI  - The role of preoperative templating in total knee arthroplasty: comparison of
      three prostheses.
AB  - Templating of preoperative radiographs is routinely recommended prior to knee
      arthroplasty. We performed this study to assess the reproducibility and accuracy
      of the templates for three commonly used knee implants (PFC, Kinemax, Scorpio).
      Six lower limb surgeons templated 10 patients for each of the three designs. The
      inter- and intra-observer reliability and accuracy was calculated. There was
      marked variation in the reliability of the templating with the tibial insert
      scoring better than the femoral and the Kinemax being the most reproducible of
      the three. In general, the intra-observer scores (kappa=0.57-0.81) were better
      than the inter-observer ones (kappa=0.21-0.60). The Scorpio was the most
      accurately templated of the three implants, with the percentage correlating with
      what was actually implanted ranging from 55% to 62% for the femur and 72% to 75%
      for the tibia, with no templated sizes more than one size different from the
      actual implant. The other implants ranged from 38% to 42% for the femur and 53%
      to 58% for the tibia with both having up to 3% more than 1 size difference from
      the actual implant. We believe that the use of templating in total knee
      arthroplasty should be interpreted with caution and we urge the development of
      more accurate prosthesis sizing techniques.

PMID- 17029815
TI  - [Evolution of the antibiotic resistance of Streptococcus pneumoniae from 1997 to
      2004 at Hotel-Dieu de France, a university hospital in Lebanon].
AB  - Various rates of Streptococcus pneumoniae with diminished susceptibility to
      Penicillin G (PNSP) are reported worldwide, while resistance to cefotaxime and
      ceftriaxone is actually increasing among S. pneumoniae. The aim of this survey
      was to determine the evolution of the susceptibility and resistance of S.
      pneumoniae at our hospital, throughout the years 1997-2004. 582 S. pneumoniae
      strains, isolated from different patients with pulmonary disease, otitis media,
      bacteremia and/or meningitis have been observed. MIC to benzylpenicillin (P),
      ampicillin (AMP) and ceftriaxone (CRO) were determined by E-TEST. Susceptibility
      to erythromycin (ERY), cotrimoxazole (SXT), tetracycline (TE) and rifampicin (RA)
      were determined by agar diffusion. All tests were interpreted according to CA-SFM
      guidelines. The percentage of PNSP varied between 49.6 and 69%. S. pneumoniae
      with reduced susceptibility to benzylpenicillin had stable rates, while fully
      resistant S. pneumoniae decreased significantly. Resistance to ampicillin varied
      alongside with penicillin with a decrease of fully resistant S. pneumoniae.
      Strains intermediate to ceftriaxone also decreased significantly while those
      fully resistant were not detected, except for 1999 (1 strain). The resistance
      (I+R) to SXT and TE remained stable with small variations, but resistance to ERY
      increased up to 43% of isolated strains in 2004. Resistance to LVX and RA was
      absent, with unexpected levels for RA (1 and 5%) in 2002 and 2003.

PMID- 17029817
TI  - Judgments of causal efficacy under constant and changing interevent
      contingencies.
AB  - How do people judge constant and varying interevent contingencies? In two
      experiments, 150 college students rated the efficacy of a potential cause (an
      experimental fertilizer) of an effect (a plant's blooming). The prevailing
      probabilistic interevent relation could remain constant for the entirety of the
      problem or it could change without warning at the midway point: by contingency
      reversal, by shifting from noncontingency to contingency, or by shifting from
      contingency to noncontingency. Participants' trial-by-trial ratings sensitively
      tracked the prevailing positive, negative, and noncontingent interevent
      relations, even those that entailed an unsignaled change in contingency. Changes
      in specific cells of the 2 x 2 contingency table differentially affected
      participants' response to the altered interevent relations. All of this evidence
      was well described by an associative account of contingency and causal judgments.

PMID- 17029818
TI  - Derivation of V function for LR 115 SSNTD from its sensitivity to 220Rn in a
      diffusion chamber.
AB  - The sensitivity of the LR 115 detector inside a diffusion chamber to (220)Rn gas
      concentration is dependent on the removed active layer thickness during chemical
      etching. This dependence is related to the V function for the LR 115 detector
      (where V is the ratio between the track etch velocity V(t) and the bulk etch
      velocity V(b)) and the geometry of the diffusion chamber. The present paper
      presents the experimentally determined relationship between the sensitivity of
      the LR 115 detector inside a Karlsruhe diffusion chamber (determined from the
      number of etched tracks completely penetrating the active cellulose nitrate
      layer) and the removed active layer thickness. These data were used to derive the
      V function for the LR 115 detector, which took the functional form of the Durrani
      Green's function, i.e., V=1+((a1e-)(a2R+a3e(-a)4R))(1(-e)(-a5R)), with the best
      fitted constants as a(1)=14.50, a(2)=0.50, a(3)=3.9 and a(4)=0.066.

PMID- 17029819
TI  - Measurements of the half-life of 246Cm and the alpha-decay emission probabilities
      of 246Cm and 250Cf.
AB  - The alpha-decay half-life of Cm246 has been measured to be T(1/2)=4706 (40)yr by
      means of the alpha-counting of ingrowth activity following the decay of a mass
      separated source of the Cf250 parent nuclide. The alpha-decay emission
      probabilities of Cm246 and Cf250 have also been determined with high precision
      and have been compared with results from previous measurements. A new alpha-decay
      branch of Cm246 to the 4(+) level of the ground-state band of the Pu242 daughter
      nucleus has been identified and characterized.

PMID- 17029820
TI  - RETRACTED: Synthesis of [(18)F]-labeled N(3)-substituted thymidine analogs: N(3)
      [(18)F]fluoroethyl thymidine (N(3)-[(18)F]-FET) and N(3)-[(18)F]fluoropropyl
      thymidine (N(3)-[(18)F]-FPRT) for PET.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy The
      Publisher apologizes for any inconvenience this may cause.

PMID- 17029821
TI  - Nonlinear oscillatory reaction of catalase induced by gradual entry of substrate.
AB  - Characteristic oscillatory reactions were observed when hydrogen peroxide
      migrated through semipermeable membrane into a solution of catalase. Measurements
      were made with DO and an mV meter. Oscillation clearly occurred in the range
      between 25 degrees C and 37 degrees C and between pH 6.0 and pH 7.6. It was also
      shown that a driving force for the permeation of H2O2, which was the cause of the
      oscillations, was a deviation from its equilibrium concentration. We made
      simulations for oscillatory reactions on the basis of these findings. The result
      indicated that considering the evaporation of O2 was necessary in order to
      interpret the oscillatory reactions of catalase in addition to the slow entry of
      substrate caused by deviation from the equilibrium concentration. The fact that
      oscillations arise by using this method may provide an important insight into the
      study of enzyme reactions mediated by membranes in living systems, because many
      enzyme reactions take place with the mediation of a biomembrane.

PMID- 17029822
TI  - Protein folding and wring resonances.
AB  - The polypeptide chain of a protein is shown to obey topological constraints which
      enable long range excitations in the form of wring modes of the protein backbone.
      Wring modes of proteins of specific lengths can therefore resonate with molecular
      modes present in the cell. It is suggested that protein folding takes place when
      the amplitude of a wring excitation becomes so large that it is energetically
      favorable to bend the protein backbone. The condition under which such structural
      transformations can occur is found, and it is shown that both cold and hot
      denaturation (the unfolding of proteins) are natural consequences of the
      suggested wring mode model. Native (folded) proteins are found to possess an
      intrinsic standing wring mode.

PMID- 17029823
TI  - Chaos in a minimal model of the alternative pathway of the complement system.
AB  - In previous work, we introduced a minimal model of the alternative pathway of the
      complement. We also limited our analysis to a reduced set of parameter values
      because, for some parameters, experimentally supported estimates were not found.
      On the other hand, changes in value of some parameters may be a result of a
      pathological condition. Therefore, here we extend our analysis and include a
      wider range of values of five of the physiologically relevant parameters. For all
      the parameters considered, we observe chaotic oscillations, and we construct
      bifurcation diagrams using Poincare sections of local maxima.

PMID- 17029824
TI  - An EPR investigation on the structural heterogeneity in copper azurin and
      plastocyanin.
AB  - The effects of cooling rate and of solvent properties on the active site
      heterogeneity of two copper proteins, azurin and plastocyanin, have been
      investigated at low temperature by electron paramagnetic resonance spectroscopy.
      The spectra of theses proteins have been analyzed, by an accurate computer
      simulation, in terms of a distribution of some relevant spin-Hamiltonian
      parameters. The results show that the structural heterogeneity of both proteins,
      quantified by the width of the distribution in the g and A tensors, is affected
      by both the freezing procedure and the solvent composition. In particular, the g
      distribution width is found to be reduced in the slow cooling regime; such a
      reduction appearing more significant when glycerol is added to the protein
      solutions. Despite of the similarity in the copper ion microenvironments of the
      two proteins, the effects are more pronounced in azurin. The results are
      discussed also in connection with the role played by the solvent and the rate of
      freezing in featuring the conformational substate landscape.

PMID- 17029825
TI  - Male-female differences in the risk of progression from first use to dependence
      upon cannabis, cocaine, and alcohol.
AB  - INTRODUCTION: We extend prior reports about the risk of dependence on specific
      drugs by providing developmental-specific risk estimates for progression from
      first use to meeting criteria for DSM-III-R dependence upon cannabis, cocaine, or
      alcohol, as well as male-female differences. METHODS: The data are from the
      National Comorbidity Survey, with a national probability sample of persons 15-44
      years old in the United States, which included many respondents who used
      cannabis, cocaine and alcohol on at least one occasion (n=3558, 1337, and 6149,
      for cannabis, cocaine, and alcohol, respectively). Survival analysis procedures
      provided cumulative risk estimates of progression from first use to dependence
      upon each drug. RESULTS: The estimated risk of cannabis dependence among male
      cannabis users was 1% in the first year after first use, and reached a peak at 4%
      per year 2 years later, before declining. In contrast, the estimated risk of
      cannabis dependence among female cannabis users remained at 1% per year for 3
      years, without the peak. For both male and female cocaine users, the estimated
      risk for developing cocaine dependence was 5 to 6% within the first year after
      first use. Thereafter, the estimated risk declined from the peak value, with a
      somewhat faster decline for females in the next 3 years after first use. For
      alcohol, the estimated risk period extended for many years after the first drink,
      with female drinkers becoming alcohol dependent at a rate of about 1% per year;
      with somewhat higher risk for male drinkers. For both male and female drinkers,
      the period of risk for developing alcohol dependence extended for a span of more
      than 20 years since first use; for cannabis and cocaine, the estimated period of
      risk was much shorter. COMMENT: There are male-female differences in the risk of
      becoming cannabis dependent during the first several years after initiation of
      cannabis use, less pronounced male-female differences for alcohol, and relatively
      smaller male-female differences for cocaine. These results should interest
      scientists whose focus is upon the origins of male-female differences in the
      occurrence of drug dependence.

PMID- 17029826
TI  - Increased glycophorin A somatic cell variant frequency in arsenic-exposed
      patients of Guizhou, China.
AB  - Exposure to arsenic through domestic burning arsenic-containing coal causes
      various tumors in a population of Guizhou, China. The glycophorin A (GPA) assay
      is a human mutation assay detecting somatic variation in erythrocytes expressing
      the MN blood type, and was used to assess genotoxicity of arsenic-exposed
      patients. Peripheral blood was collected from 18 adult healthy subjects and 40
      arsenic-exposed patients in heparin-treated tubes. Erythrocytes were isolated,
      fixed in formalin and immuno-labeled with fluorescent antibodies against GPA,
      followed by flow cytometry analysis. Arsenic exposure increased the variant
      frequency (expressed as the number of variant red cells per 10(6) erythrocytes):
      NN, 3.7 in healthy subjects versus 21.2 in arsenic-exposed patients; N phi, 12.6
      versus 33.1; MM, 13.1 versus 110; and M phi, 5.2 versus 20.3. The total GPA
      variant frequency was increased about five-fold (34.7 in healthy subjects versus
      185 in arsenosis patients). Furthermore, the variant frequency was significantly
      higher in skin tumor-bearing patients: NN, 19.4 in arsenic-exposed non-tumor
      patients versus 31.5 in tumor-bearing patients; N phi, 29.5 versus 54.5; MM, 102
      versus 159; M phi, 15.9 versus 45.1. Total GPA variant frequency in arsenic
      exposed patients bearing skin tumors was significantly increased compared to
      patients without skin tumors (167 versus 290). The relationship between arsenic
      exposure history and GPA variant frequency was less evident. These data
      demonstrate that arsenic exposure is associated with mutations at the GPA locus,
      an effect exaggerated in patients bearing arsenic-induced skin tumors. The
      variant frequency of GPA could be a useful biomarker for arsenic exposure and
      arsenic carcinogenesis.

PMID- 17029827
TI  - Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2
      cells for the identification of potential biomarkers for PAH monitoring and risk
      assessment.
AB  - To identify potential biomarkers for the monitoring and risk assessment of
      benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53
      modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene
      exposure induced a decrease in the cell viability, but increased the antioxidant
      enzyme activity as well as the DNA and lipid damage. The p53 protein activation
      appeared to have been a downstream response to the benzo[a]pyrene-induced DNA
      damage, suggesting p53 plays important roles in the defense against
      benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be
      more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA
      damage, the activation of p53 acts as a transcriptional regulator of several
      target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and
      is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after
      the treatment of cells with benzo[a]pyrene, as well as following the induction of
      p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also
      be transcriptionally induced. The overall results suggest that benzo[a]pyrene
      leads to serious DNA damage, which leads to the transcription of the p53 gene;
      that the subsequent p53 protein accumulation up-regulates the cellular p21
      protein. Oxidative DNA damage and p53 accumulation seem to be related to
      benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental
      monitoring and risk assessment needs to be validated in the context of their
      specificity and sensitivity.

PMID- 17029828
TI  - Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of
      Alzheimer disease.
AB  - Transgenic mice carrying disease-linked forms of genes associated with Alzheimer
      disease often demonstrate deposition of the beta-amyloid as senile plaques and
      cerebral amyloid angiopathy. We have characterized the natural history of beta
      amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic
      mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1
      (dE9: deletion of exon 9). Ex vivo histochemistry showed Abeta deposition by 4
      months with a progressive increase in plaque number up to 12 months and a similar
      increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals
      showed increasing beta-amyloid deposition as CAA and plaques. Although first
      appearing at an early age, CAA progressed at a significantly slower rate than in
      the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in
      the APPswe/PS1dE9 model confirms its utility for studies of biochemical and
      pathological mechanisms underlying beta-amyloid deposition, as well as exploring
      new therapeutic treatments.

PMID- 17029830
TI  - The Gibbs conference on biothermodynamics: origins and evolution.
AB  - The Gibbs conference on biothermodynamics arose in the late 1980's as a 'self
      organized' endeavor by researchers at eleven institutions of the US. Over a
      period of 10 years these annual conferences have grown steadily in size. They
      have fostered the development of new thermodynamic approaches and their
      applications in biochemistry. By emphasizing participation by students and
      postdoctoral fellows they have contributed significantly to the career
      development of young scientists in this field.

PMID- 17029831
TI  - Heat capacities of protein functional groups.
AB  - Using a precise technique of scanning calorimetry the heat capacities of a series
      of carboxylic acids and their sodium salts, alcohols, and N-substituted amides
      have been measured from 5 to 100 degrees C. From these data, the partial molar
      heat capacities of CH2, CONH, COOH, and COONa groups have been determined. It is
      shown that the heat capacity of the CH(2) group in aqueous solution is
      independent of the type of compound used for its determination, is positive at
      low temperature, and is linearly decreasing in magnitude with an increase in
      temperature. In contrast, the heat capacities of COOH and COONa groups in aqueous
      solution are negative at room temperature and their magnitude non-linearly
      decreases with an increase in temperature. It appears that the partial heat
      capacity of CONH group in aqueous solution depends on the type of model compound
      used for its determination. These differences correlate with the difference in
      the water accessible surface area of atoms in the CONH group in different model
      compounds.

PMID- 17029832
TI  - Significant discrepancies between van't Hoff and calorimetric enthalpies. III.
AB  - The study of a wide variety of reversible reactions in solution indicates that
      the enthalpy, DeltaH(vH), which controls the temperature variation of the
      equilibrium constant for a reaction, can seldom, if ever, be taken to be
      independent of the temperature. It is also found in most cases that the values
      for DeltaH(vH), properly evaluated as varying with the temperature, differ
      significantly from the values for the enthalpy, DeltaH(cal), determined by direct
      calorimetry under the same experimental conditions. In a continuing search for
      reactions which show agreement between DeltaH(vH) and DeltaH(cal), we have
      studied by isothermal titration calorimetry the reactions of heptylamine with
      heptanoic acid in dodecane solution and of alpha-cyclodextrin with sodium
      heptanoate in aqueous solution.

PMID- 17029833
TI  - Competitive electrostatic binding of charged ligands to polyelectrolytes:
      practical approach using the non-linear Poisson-Boltzmann equation.
AB  - We have developed a practical analytical treatment of the non-linear Poisson
      Boltzmann (P-B) equation to characterize the strong but non-specific binding of
      charged ligands to DNA and other highly charged macromolecules. These reactions
      are notable for their strong salt dependence and anti-cooperativity, features
      which the theory fully explains. We summarize analytical results for
      concentration profiles and ion binding in various regimes of surface curvature
      and ionic strength, and show how counterion size and charge distribution may
      influence competitive binding. We present several practical applications of the
      formalism, showing how to estimate the ligand concentration needed to effectively
      compete with a given buffer salt, and how to calculate the amounts of counterion
      species bound at various distances from the DNA surface under given bulk solution
      conditions. We cast our results into the form of a Scatchard binding isotherm,
      showing how the apparent binding constant K(obs) and S = -dlog K (obs )d log[M
      (+)] can be predicted from the basic theory. Anti-cooperativity arises naturally
      without steric repulsion, and binding curves can be fitted with K(obs) and
      effective charge as the only free parameters. We extend the analytical P-B
      analysis to an arbitrary number of counterion species, and apply the results to
      fit and predict three-ion competition data.

PMID- 17029834
TI  - Thermodynamics of protein unfolding: questions pertinent to testing the validity
      of the two-state model.
AB  - We discuss a number of questions pertaining to the analysis of data to extract
      thermodynamic parameters for the reversible unfolding of proteins. Simulations
      are presented to illustrate problems in trying to test the validity of the two
      state model, vis-a-vis a more complicated unfolding model. A conceptual and
      practical problem is how to consider the unfolded state and how to relate the
      observed signal to this state. We discuss the idea that the unfolded state can be
      described as a single macrostate, comprising a distribution of microstates having
      different degrees of solvent-accessible surface area. We also discuss the
      possibilities and thermodynamic consequences of having more than one unfolded
      state and of having a denaturant which both stabilizes and destabilizes the
      protein's native state.

PMID- 17029835
TI  - Neutrophil dysfunction after biomaterial contact in an in vitro model of
      cardiopulmonary bypass.
AB  - OBJECTIVE: Cardiopulmonary bypass (CPB) induces neutrophil degranulation and
      superoxide anion production in vivo. We hypothesized that CPB-associated
      neutrophil dysregulation alters neutrophil adhesion to vascular endothelial cells
      and the extracellular matrix. METHODS: We, therefore, recirculated neutrophils in
      polyvinyl chloride (PVC) tubing using a roller pump model and thereafter measured
      adhesion to cultured microvascular endothelial cells and gelatin-coated surfaces.
      Recirculation-induced neutrophil priming or exhaustion was tested by boosting
      with phorbol myristate-acetate (PMA) or N-formyl-methiolyl-leucyl-phenylalanine
      (FMLP) before quantification of adhesion. RESULTS AND CONCLUSION: After
      recirculation, neutrophils retained their adhesive capability to vascular
      endothelial cells, whereas adhesion to gelatin increased. This increase was not
      seen when the neutrophils were recirculated with a rotator instead of a roller
      pump, indicating that not only the pump mode but also foreign surface contact was
      of significance. The neutrophil PMA response after recirculation was not altered
      compared to resting neutrophils prestimulated with PMA. Recirculated neutrophils
      adhered less to cultured vascular endothelial cells after FMLP activation and
      more to gelatin compared to resting neutrophils prestimulated with FMLP. It is
      conceivable that dysregulation of neutrophil adhesive capability may play a part
      in the development of tissue damage after CPB.

PMID- 17029836
TI  - Estrus behavior and fecal steroid profiles in the Asiatic lion (Panthera leo
      persica) during natural and gonadotropin-induced estrus.
AB  - In this paper the behavior of the Asiatic lion was studied during natural and
      gonadotropin-induced estrus in relation to fecal estradiol and progesterone
      concentration. The average length of estrus was 5.4 days and no significant
      difference was observed between natural and gonadotropin-induced estrus.
      Vocalization and rolling were the major estrus behavioral activities of Asiatic
      lions and the frequency of these activities were similar in both natural and
      gonadotropin-induced estrus and treatment with exogenous gonadotropin did not
      alter estrus behavioral activities. A significant positive correlation was
      observed between fecal estradiol and frequency of estrus behavior during natural
      and gonadotropin-induced estrus. Following gonadotropin treatment estrus could be
      induced in 69% of animals and these induced animals ovulated following hCG
      treatment. This study reports for the first time the successful use of the non
      invasive fecal steroid assay for monitoring the induction of estrus and ovulation
      in the Asiatic lion.

PMID- 17029837
TI  - Protein machine model of enzymatic reactions gated by enzyme internal dynamics.
AB  - The slow character of conformational transition dynamics in native proteins,
      recently becoming more and more apparent, makes conventional theories of chemical
      reactions inapplicable for the description of enzymatic reactions. Any
      contemporary statistical theory of biochemical processes has to be based on a
      possibly simple but realistic model of microscopic dynamics of participating
      biomolecules. In a model considered in this paper the dynamics of enzymatic
      protein is approximated by a quasi-continuous diffusive motion of its solid-like
      structural elements relative to each other. The enzymatic reaction is assumed to
      involve three steps (a covalent tranformation preceded and followed by
      association-dissociation processes with the substrate and the product), each step
      being gated by conformational diffusion. In general, the reaction proceeds in
      three stages: initial, transient and steady-state. Carefully approximated
      analytical formulae describing the kinetics in each stage are derived. In the
      limit of the fast internal dynamics of the enzyme, when compared to the local
      chemical transformations, the initial stage of reaction, dependent on the initial
      distribution of enzyme conformations, is absent and all the formulae describing
      the remaining two stages simplify to those provided by the classical theory of
      Haldane. However, following recent studies, the rule seems to be that it is the
      conformational dynamics of the enzyme, and not the details of chemical mechanism,
      that affects the rate of enzymatic reaction. Apart from the possibility of the
      initial inhomogeneous kinetics, the important result obtained in the limit of
      slow conformational dynamics is that the kinetic mechanisms of a reaction differ
      in general between the transient and steady-state stages. Possibilities of
      carrying out an experimentum crucis directly discrediting the conventional
      approach are considered.

PMID- 17029838
TI  - New method for incorporating solvent influence into the evaluation of X-ray
      scattering intensity of proteins in solution.
AB  - A new method, the surface integration method, is presented for taking into
      account the influence of solvent on the intensity of X-ray scattered from
      proteins in solution. It requires no averaging numerically over the solute
      orientation. The solvent is modeled by a continuous medium with electrons of
      uniform density. This method is applied to amino acids, peptides and native
      proteins to confirm its effectiveness. The solvent influence on the normalized
      scattering intensity I(K) I(0) is more noticeable for larger solutes and at
      larger scattering angles, where I(K) is the intensity of scattered X-ray with the
      magnitude of scattering vector K.

PMID- 17029839
TI  - Fluorescence and binding properties of phenazine derivatives in complexes with
      polynucleotides of various base compositions and secondary structures.
AB  - The interactions of two phenazine derivatives, one with a neutral chromophore
      (glycoside) and the other with a cationic one (quaternary salt), with various
      synthetic single- and double-stranded polynucleotides and natural DNA were
      studied by fluorescence techniques, conducting measurements of steady-state
      fluorescence intensity and polarization degree as well as fluorescence lifetime.
      These dyes show fluorescence quenching upon intercalation into the GC sequences
      of the double-stranded nucleic acids and an increase in fluorescence emission and
      lifetime upon incorporation into the AT and AU sequences. GC base pairs in
      continuous deoxynucleotide sequences were found to be preferred as binding sites
      for both phenazines, in contrast to AT base pairs. On the contrary, the
      continuous ribonucleotide GC sequence binds the phenazines more weakly than does
      the AU sequence. With regard to the interaction of the phenazines with single
      stranded polynucleotides, a stacking interaction of the dye chromophores with the
      nucleic bases was observed. In that case the guanine residue quenches the
      cationic phenazine fluorescence, while the stacking interaction with the other
      bases results in an increase in the fluorescence quantum yield. Unlike the
      cationic dye, the fluorescence of the neutral phenazine was quenched by both
      purine bases.

PMID- 17029840
TI  - Secondary solvent effects on the circular dichroism spectra of polypeptides in
      non-aqueous environments: influence of polarisation effects on the far
      ultraviolet spectra of alamethicin.
AB  - Secondary solvent effects on the far ultraviolet circular dichroism spectra of
      the polypeptide alamethicin have been studied systematically in a series of
      alcohols. The magnitudes of the shifts have been correlated with the physical
      properties of the solvents in an attempt to discover the underlying physical
      principles responsible for these shifts. The solvent effect in non-aqueous
      solvents generally produces spectral transitions with peaks found at longer
      wavelengths than those in aqueous solution, and is correlated with increasing
      refractive indices and with decreasing dielectric constants of the solvents. It
      appears that polarisation effects are the major contributors to the interactions
      between the chromophore and solvent molecules, and hence give rise to the red
      shift. It is clear that this secondary solvent effect is an important factor
      which should be considered in the examination and estimation of polypeptide
      secondary structures in non-aqueous solvents and membranes.

PMID- 17029841
TI  - Antinociceptive activity of Amazonian Copaiba oils.
AB  - Copaiba oil resins are extensively commercialized in Brazil as capsules or crude
      oil and used as anti-inflammatory and anti-septic. Comparative pharmacological
      studies between different species of Copaiba oils are scarce. In the present work
      we compared the antinociceptive activity of two Amazonian Copaiba oils (Copaifera
      multijuga Hayne and Copaifera reticulata Ducke, Fabaceae) administered by oral
      route using peripheral (acetic acid-induced abdominal writhing and formalin),
      spinal (tail flick) and supra-spinal (hot plate) models. Results demonstrated
      that the Copaiba oils did not develop toxic effects. Doses ranging from 30 to 150
      mg/kg were enough to significantly develop peripheral antinociceptive effect. All
      Copaiba oils demonstrate central activity but with less effect on supra-spinal
      regions of the brain. Administration of the opioid receptor antagonist, naloxone
      completely inhibited the antinociceptive effect induced by both Copaiba oils. Our
      results indicate that Copaiba oils demonstrate peripheral and central
      antinociceptive effect. This new comprobate effect may be useful in the treatment
      of algesic disorders.

PMID- 17029842
TI  - AUTO3DEM--an automated and high throughput program for image reconstruction of
      icosahedral particles.
AB  - AUTO3DEM is an automation system designed to accelerate the computationally
      intensive process of three-dimensional structure determination from images of
      vitrified icosahedral virus particles. With minimal user input and intervention,
      AUTO3DEM manages the flow of data between the major image reconstruction
      programs, monitors the progress of the computations, and intelligently updates
      the input parameters as the resolution of the model is improved. It is designed
      to be used on any computer running the Linux or UNIX operating systems and can be
      run in parallel mode on multi-processor systems.

PMID- 17029843
TI  - SCA: symmetry-based center assignment of 2D projections of symmetric 3D objects.
AB  - A method for finding the center of cryo-EM images which correspond to the
      projections of a symmetric 3D structure, based on mathematical properties of
      symmetry adapted functions and the Fourier-Bessel transform, is presented. It is
      a model independent one-step procedure with no parameters to be chosen by the
      user. The proposed method is tested in one synthetic tetrahedral case with
      different noise levels and in two real cases with D7 and icosahedral symmetries.

PMID- 17029844
TI  - Structure and thermodynamics of the tubulin-stathmin interaction.
AB  - Oncoprotein 18/stathmin (stathmin) is a phosphorylation-controlled key regulator
      of microtubule dynamics. In recent years, substantial efforts were undertaken to
      characterize the complex formed between tubulin and the intrinsically disordered
      stathmin molecule. Here, I summarize and illustrate the current structural and
      thermodynamic studies on the tubulin-stathmin interaction. Based on these and on
      functional information I formulate an updated molecular mechanism on how tubulin
      binding by stathmin regulates microtubule dynamics.

PMID- 17029845
TI  - Ab initio resolution measurement for single particle structures.
AB  - A computational method is described that allows the measurement of the signal-to
      noise ratio and resolution of a three-dimensional structure obtained by single
      particle electron microscopy and reconstruction. The method does not rely on the
      availability of the original image data or the calculation of several structures
      from different parts of the data that are needed for the commonly used Fourier
      Shell Correlation criterion. Instead, the correlation between neighboring Fourier
      pixels is calculated and used to distinguish signal from noise. The new method
      has been conveniently implemented in a computer program called RMEASURE and is
      available to the microscopy community.

PMID- 17029846
TI  - Flap opening dynamics in HIV-1 protease explored with a coarse-grained model.
AB  - We present a one-bead coarse-grained model that enables dynamical simulations of
      proteins on the time scale of tens of microseconds. The parameterization of the
      force field includes accurate conformational terms that allow for fast and
      reliable exploration of the configurational space. The model is applied to the
      dynamics of flap opening in HIV-1 protease. The experimental structure of the
      recently crystallized semi-open conformation of HIV-1 protease is well reproduced
      in the simulation, which supports the accuracy of our model. Thanks to very long
      simulations and extensive sampling of opening and closing events, we also
      investigate the thermodynamics and kinetics of the opening process. We have shown
      that the effect of the solvent slows down the dynamics to the experimentally
      observed time scales. The model is found to be reliable for application to
      substrate docking simulations, which are currently in progress.

PMID- 17029847
TI  - Multi-resolution anchor-point registration of biomolecular assemblies and their
      components.
AB  - An atomic scale interpretation facilitates the assignment of functional
      properties to 3D reconstructions of macromolecular assemblies in electron
      microscopy (EM). Such a high-resolution interpretation is typically achieved by
      docking the known atomic structures of components into the volumetric EM maps.
      Docking locations are often determined by maximizing the cross-correlation
      coefficient of the two objects in a slow, exhaustive search. If time is of
      essence, such as in related visualization and image processing fields, the
      matching of data is accelerated by incorporating feature points that form a
      compact description of 3D objects. The complexity reduction afforded by the
      feature point representation enables a near-instantaneous matching. We show that
      such reduced matching can also deliver robust and accurate results in the
      presence of noise or artifacts. We therefore propose a novel multi-resolution
      registration technique employing feature-based shape descriptions of the
      volumetric and structural data. The pattern-matching algorithm carries out a
      hierarchical alignment of the point sets generated by vector quantization. The
      search-space complexity is reduced by an integrated tree-pruning technique, which
      permits the detection of subunits in large macromolecular assemblies in real
      time. The efficiency and accuracy of the novel algorithm are validated on a
      standard test system of homo-oligomeric assemblies.

PMID- 17029848
TI  - Conformational analysis of Amphotericin B.
AB  - Within a theoretical approach to the problem of antifungal action of Amphotericin
      B (AmB), a conformational analysis of the neutral and zwitterionic form of this
      antibiotic in vacuo was performed by the MM2P and AM1 methods. The analysis was
      carried out with regard to the mutual orientation of the macrolidic and
      glycosidic fragments of the molecule, which is defined by the phi and psi steric
      angles. This orientation defines the overall shape of the molecule and is
      postulated to be important for the antifungal action of the drug. As a result of
      the MM2P calculations, phi, psi steric energy and population maps were prepared.
      Several conformers were found on these maps but only two of them (one each for
      the zwitterionic and the neutral forms of the antibiotic) were previously
      observed experimentally for isolated molecules. Our other calculated conformers
      were not observed experimentally but we propose that they may also appear in the
      AmB channel structure. The results of our conformational analysis were compared
      with experimental NMR data (nuclear Overhauser effects between selected hydrogen
      atoms) obtained previously. New structural information obtained for AmB in the
      present work will be useful for building a molecular model of AmB-target
      interactions as well as for designing new derivatives of AmB.

PMID- 17029849
TI  - A theory on the instability of tubular membranes to the periodic conformation by
      laser tweezers.
AB  - A mechanical theory to analyze the stability of tubular membranes perturbed by
      optical tweezers is proposed. I assume that the optical tweezers cause the
      temporal elevation of hydrostatic pressure inside tubular membranes due to the
      thermal expansion of solvent water, and I relaxed the conservation of volume per
      unit length which was strictly maintained in old theories based on the well-known
      Rayleigh instability. The mechanical energy composed of bending rigidity,
      interfacial tension, and hydrostatic pressure terms can explain the condition of
      the previously observed peristaltic and pearling instability. The spontaneous
      curvature of the membrane is postulated in the theory. The enhanced pressure
      causes the tubules to enter a peristaltic state with a spinodal line in the phase
      diagram.

PMID- 17029850
TI  - Finite one-dimensional spin systems as models of biopolymers.
AB  - New models are proposed for describing various properties of biopolymers,
      especially those of proteins and nucleic acids. Each model is constituted of a
      set of spins arranged on a chain, and each pair of spins produces an interaction.
      We examine the transitions of these spin systems between the ground state and the
      disordered state. It is found that the transitions of the present spin systems
      demonstrate various properties in response to values of the so-called interaction
      energy. If we define interaction energy parameters with no so-called frustration,
      the system exhibits two-state transitions, similar to the folding-unfolding
      transition of small proteins. The addition of frustrations to the model produces
      effects similar to those of mutations in proteins. On the other hand, if the
      interactions between two spins attenuate as a function of their separation along
      the chain, the transition of the system has characteristics similar to those of
      nucleic acids. Thus, the present spin systems can offer a unified view of the
      folding-unfolding transition of biopolymers in terms of differences in the
      pairwise interactions between spins. Based on our models, we propose a condition
      for two-state transition behavior for proteins.

PMID- 17029851
TI  - Steady state approximation in the minimal model of the alternative pathway of
      complement.
AB  - Complement is a response mechanism of the immune system. Two initiation pathways
      have been characterized for complement. The classical pathway is antibody
      mediated while the alternative pathway is not. Since the alternative pathway is
      independent of antibodies, it is always active. For the alternative pathway we
      have previously developed a minimal model. Using parameters within physiological
      bounds, the model showed complex behavior also within physiological bounds. Thus
      the model seems to be an appropriate representation of the alternative pathway
      response. By applying a steady state assumption to the Michaelis Menten step of
      the minimal model, we reduce the number of variables from six to five. A
      comparison between the dynamics of the minimal and contracted models reveals that
      the two descriptions may not be compatible. Although both systems show chaotic
      behavior it occurs in different regions of parameter space.

PMID- 17029852
TI  - Photoelectric properties of chlorophyll and carotene solutions in nematic liquid
      crystal located between semiconducting electrodes.
AB  - The photopotential and photocurrent generation for chlorophyll a, beta-carotene
      and a mixture of these pigments dissolved in nematic liquid crystal and located
      between transparent semiconducting electrodes were measured. Both pigments
      exhibit photopotential and photocurrent generation. From the photocurrent
      amplitudes it follows that the efficiency of electron transfer to a
      semiconducting electrode from beta-carotene is higher than from chlorophyll
      alpha. The photocurrent amplitude of the pigment mixture is slightly lower than
      that calculated as a sum of amplitudes of pigments located in separated cells.
      This difference can be explained by secondary effects, such as competition
      between carotene and chlorophyll molecules in a process of adsorption on a
      semiconducting electrode. Therefore it seems that no charge transfer complexes of
      chlorophyll and carotene are formed in the investigated model system.

PMID- 17029853
TI  - Mixed-mode oscillations in a self-replicating dimerization mechanism.
AB  - Recently, self-replicating molecules have been synthesized in the laboratory by
      Rebek. Given the importance of such molecules, we proposed a simple model of a
      self-replicating dimer, which works as a template for its own formation. Here we
      consider a three variable model. For the model, we obtain mixed-mode and chaotic
      oscillations. Also, we find coexistence between two periodic attractors as well
      as a periodic and a chaotic attractor.

PMID- 17029854
TI  - A pulsed field gradient NMR study of the aggregation and hydration of
      parvalbumin.
AB  - Pulsed field gradient NMR is a convenient alternative to traditional methods for
      measuring diffusion of biological macromolecules. In the present study, pulsed
      field gradient NMR was used to study the effects of calcium binding and hydration
      on carp parvalbumin. Carp parvalbumin is known to undergo large changes in
      tertiary structure with calcium loading. The diffusion coefficient is a sensitive
      guide to changes in molecular shape and in the present study the large changes in
      tertiary structure were clearly reflected in the measured diffusion coefficient
      upon calcium loading. The (monomeric) calcium-loaded form had a diffusion
      coefficient of 1.4 x 10(-10) m(2) s(-1) at 298 K, which conforms with the
      structure being a nearly spherical prolate ellipsoid from X-ray studies. The
      calcium-free form had a significantly lower diffusion coefficient of 1.1 x 10(
      10) m(2) s(-1). The simplest explanation consistent with the change in diffusion
      coefficient is that the parvalbumin molecules form dimers upon the removal of
      Ca(2+) at the protein concentration studied (1 mM).

PMID- 17029855
TI  - pK(a) calculations along a bacteriorhodopsin molecular dynamics trajectory.
AB  - Electrostatic calculations of pK(a-values) are reported along a 400 ps molecular
      dynamics trajectory of bacteriorhodopsin. The sensitivity of calculated pK(a)
      values to a number of structural factors and factors related to the modelling of
      the electrostatics are also studied. The results are very sensitive to the choice
      of internal dielectric constant of the protein (in the interval 2-4). Moreover it
      is important to include internal water molecules and to average over a long
      enough portion ( approximately 100 ps) of an equilibrium molecular dynamics
      trajectory. The internal waters are necessary to get an ion-counter ion complex
      with the Schiff base and Arg 82 protonated and the aspartic groups (85 and 212)
      deprotonated. The fluctuations along the MD-trajectory do not change the
      protonation state of internal residues at neutral pH. However, at other pH values
      the averaging along a trajectory maybe crucial to get correct protonation states.
      A relationship is found between the arginine group 82, the aspartic group 85 and
      the glutamate group 204. Glu 204 is protonated in the ground state but the pK(a)
      value decreases towards deprotonation when the chromophore isomerizes into the
      cis state.

PMID- 17029856
TI  - Kinetic model for carbon partitioning in Solanum tuberosum tubers stored at 2
      degrees C and the mechanism for low temperature stress-induced accumulation of
      reducing sugars.
AB  - Exposure to low but nonfreezing temperatures induces the breakdown of starch and
      the accumulation of sucrose, glucose and fructose in potato tubers, a complex
      phenomenon known as low-temperature sweetening (LTS). A kinetic model for the
      degradation of starch to sucrose, fructose, glucose, hexose phosphates and carbon
      dioxide in 2 degrees C-stored mature Solanum tuberosum cv. Norchip (LTS
      sensitive) and Solanum tuberosum seedlling ND860-2 (LTS-tolerant) tubers is
      presented in this work. Analysis of sugar accumulation data in tubers grown in
      1993 and 1994 showed no significant differences in the rates of conversion of
      starch to hexose phosphates and hexose phosphates to sucrose for both cultivars
      (P > 0.05). The rate constant corresponding to invertase activity was 2.3 day(-1)
      for Norchip tubers and 1.1 day(-1) for ND860-2 tubers grown in 1993 (P < or =
      0.05); however, no significant differences were observed in invertase activity
      for 1994-grown tubers (P > 0.05). The accumulation of the reducing sugars
      fructose and glucose was found to be dependent on the relative difference in rate
      constants corresponding to invertase activity and glycolytic/respiratory
      capacity. This difference was 3-4 fold greater for Norchip in 1993, and 4-6 fold
      greater for Norchip in 1994, than for ND860-2 (P < or = 0.05). Results from the
      analysis also suggest that the amount of available starch for degradation was
      greater in Norchip tubers than ND860-2 tubers (P < or = 0.05). Our analysis
      suggests that tubers with decreased invertase activity coupled to increased
      glycolytic/respiratory capacity should be more tolerant to low-temperature
      stress.

PMID- 17029857
TI  - Resolving multiple protein conformers in equilibrium unfolding reactions: a time
      resolved emission spectroscopic (TRES) study of Azurin.
AB  - Unlike steady-state spectrofluorimetry, time-resolved emission spectroscopy
      (TRES) can resolve emissions from fluorophores with similar quantum yields and
      overlapping steady-state emission spectra. Time-resolved emission studies of the
      protein-intrinsic fluorophore, tryptophan (Trp), can thus potentially be used to
      examine protein conformational heterogeneity in solution, as well as to
      investigate the existence of populated intermediate structural states in
      equilibrium unfolding reactions of single-tryptophan proteins. Here, the single
      Trp copper protein, azurin, is examined in various concentrations of guanidine
      hydrochloride (GdnCl) with its disulphide bond in an intact state. Interestingly,
      multiple envelopes of Trp emission are observed in all TRES spectra acquired,
      instead of just two emission envelopes (corresponding to the native and unfolded
      states) expected from two-state unfolding. These envelopes appear to be centred
      around the same set of emission wavelengths in different TRES spectra, and only
      intensities and decay rates vary with the concentration of denaturant used. This
      suggests that structural states representing different levels of exposure of Trp
      to the aqueous solvent might, in fact, be populated at equilibrium during the
      unfolding of azurin by GdnCl.

PMID- 17029858
TI  - Osmotic stress induces a phase transition from interdigitated gel phase to
      bilayer gel phase in multilamellar vesicles of dihexadecylphosphatidylcholine.
AB  - We have investigated the effects of poly(ethylene glycol) (PEG) on the structure
      and phase behavior of multilamellar vesicles of dihexadecylphosphatidylcholine
      (DHPC-MLVs) using an X-ray diffraction method. At low concentrations of PEG-6K
      (MW = 7500), DHPC-MLVs were in an interdigitated gel (L(beta)I) phase, a gel
      phase with interdigitated hydrocarbon chains. At around 24% (w/v) PEG 6K, a phase
      transition from the L(beta)I phase to a bilayer gel phase occurred in the DHPC
      MLVs, and above this concentration, they were in a bilayer gel phase. On the
      other hand, ethylene glycol (EG), the monomer of PEG, did not induce this phase
      transition in the DHPC-MLVs. A mechanism of this phase transition is proposed and
      discussed; a decrease in the repulsive interaction between the head groups of the
      phospholipids in the bilayer gel phase with an increase in PEG concentration,
      which is due to a decrease in the cross-sectional area of the head group region
      by osmotic stress, may be the main reason for this phase transition.

PMID- 17029859
TI  - Forensic odontologists successfully identify tsunami victims in Phuket, Thailand.
AB  - More than a year has elapsed since the seaquake in South-East Asia in December
      2004, and more than 92% of the non-Thai victims have been identified. About 80%
      of the non-Thai victims were identified by dental information. This high success
      rate of dental identification in Thailand was a matter of surprise for many
      forensic experts. Identification based on dental information is a highly
      efficient, reliable and rapid procedure. The conclusions drawn from the
      identification of tsunami victims in Thailand were recently discussed at the 17th
      Meeting of the Standing Committee on Disaster Victim Identification of Interpol
      in Lyon, and may be used to formulate new guidelines for the identification of
      victims.

PMID- 17029860
TI  - The chronology of third molar mineralization in the Austrian population--a
      contribution to forensic age estimation.
AB  - The aim of the present study was to determine the chronology of third molar
      mineralization and to establish Austrian reference data. Therefore, a cross
      sectional study was undertaken by evaluating 610 panoramic radiographs in order
      to assess the mineralization status of the mandibular third molars of Austrian
      male and female individuals (275 males and 335 females) between the ages of 12
      and 24. The evaluation was carried out using the eight grade scheme of Demirjian
      et al. (1973). Mean ages, standard deviations, standard errors and percentile
      distributions are presented for each stage of development. Significant
      differences between the left and right mandibular third molars were not found.
      Males reach the developmental stages earlier than females, statistically
      significant differences were noted in stages E and F. Both mandibular third
      molars were observed in the majority of the individuals of the Austrian sample
      (477 individuals, 78.2%). For medicolegal purposes the likelihood of whether an
      Austrian individual is older than 18 years or not was determined.

PMID- 17029861
TI  - Handling manipulated evidence.
AB  - Bayesian Networks have been advocated as useful tools to describe the relations
      of dependence/independence among random variables and relevant hypotheses in a
      crime case. Moreover, they have been applied to help the investigator structure
      the problem and evaluate the impact of the observed evidence, typically with
      respect to the hypothesis of guilt of a suspect. In this paper we describe a
      model to handle the possibility that one or more pieces of evidence have been
      manipulated in order to mislead the investigations. This method is based on
      causal inference models, although it is developed in a different, specific
      framework.

PMID- 17029862
TI  - Kinematic, kinetic and EMG patterns during downward squatting.
AB  - The aim of this study was to investigate the kinematic, kinetic, and
      electromyographic pattern before, during and after downward squatting when the
      trunk movement is restricted in the sagittal plane. Eight healthy subjects
      performed downward squatting at two different positions, semisquatting (40
      degrees knee flexion) and half squatting (70 degrees knee flexion).
      Electromyographic responses of the vastus medialis oblique, vastus medialis
      longus, rectus femoris, vastus lateralis, biceps femoris, semitendineous,
      gastrocnemius lateralis, and tibialis anterior were recorded. The kinematics of
      the major joints were reconstructed using an optoelectronic system. The center of
      pressure (COP) was obtained using data collected from one force plate, and the
      ankle and knee joint torques were calculated using inverse dynamics. In the
      upright position there were small changes in the COP and in the knee and ankle
      joint torques. The tibialis anterior provoked the disruption of this upright
      position initiating the squat. During the acceleration phase of the squat the COP
      moved posteriorly, the knee joint torque remained in flexion and there was no
      measurable muscle activation. As the body went into the deceleration phase, the
      knee joint torque increased towards extension with major muscle activities being
      observed in the four heads of the quadriceps. Understanding these kinematic,
      kinetic and EMG strategies before, during and after the squat is expected to be
      beneficial to practitioners for utilizing squatting as a task for improving motor
      function.

PMID- 17029863
TI  - Control of head stability during gait initiation in young and older women.
AB  - Transition tasks between static and dynamic situations may challenge head
      stabilization and balance in older individuals. The study was designed to
      investigate differences between young and older women in the upper body motion
      during the voluntary task of gait initiation. Seven young (25+/-2.3 years) and
      seven older healthy women (78+/-3.4 years) were required to stand on a force
      platform and initiate walking at their self-selected preferred speed. Angles of
      head, neck and trunk were measured by motion analysis in the sagittal plane and a
      cross-correlation analysis was performed on segments pairs. Variability of head
      and neck angular displacements, as indicated by average standard deviation, was
      significantly greater in the older than in the young participants. The young
      women maintained dynamic stability of the upper body, as forward flexion of the
      trunk was consistently counteracted by coordinated head-neck extension.
      Differently, movement patterns employed by the older women also included a rigid
      motion of all upper body segments leaning forward as a single unit. These results
      demonstrated that older women perform the transition from standing to walking
      with greater variability in the patterns of upper body motion compared to young
      women.

PMID- 17029864
TI  - Cancer survivors information seeking behaviors: a comparison of survivors who do
      and do not seek information about cancer.
AB  - OBJECTIVE: To examine the cancer information seeking behaviors and preferences of
      cancer survivors. METHODS: This cross-sectional study used the National Cancer
      Institute's 2003 Health Information National Trends Survey data to evaluate 619
      cancer survivors. RESULTS: Two-thirds (67.5%, n = 418) of the survivors sought
      cancer information (InfoSeek) and 32.5% (n = 201) did not (NoInfoSeek).
      Significant predictors of cancer information seeking included age (less than 65),
      gender (female), income (>US$ 25,000/year), and having a regular health care
      provider (HCP). CONCLUSION: Not all survivors actively look for cancer
      information. Although most survivors prefer receiving cancer information from
      their HCP, many turn to a variety of other sources, primarily the Internet.
      PRACTICE IMPLICATIONS: HCPs should periodically assess information seeking
      behaviors and preferences of cancer survivors and actively refer patients to the
      Internet as an extension of and enhancement to their patient interactions.
      Credible and useful websites could be identified and recommended by the HCP as a
      means to address some of the barriers identified by survivors.

PMID- 17029866
TI  - Physico-chemical properties of the heat-induced 'superaggregates' of amphotericin
      B.
AB  - The aggregation state of amphotericin B (AmB) was previously reported to modulate
      its therapeutic efficiency. As a preliminary study to test the biological effects
      of 'superaggregates' generated by heat treatment, we present spectroscopic data
      related to their formation in aqueous solutions. Drastic changes in the AmB
      aggregation state in water were shown to occur on heating at 50-60 degrees C. The
      concentration of the aggregates formed at high (A(t)) or room (A) temperature,
      and the concentration of the monomeric form (M) of AmB were calculated by
      processing absorption data. The thermally induced conversion from A to A(t)
      depends on the AmB concentration. Rayleigh scattering measurements suggest that
      the A(t) aggregates are larger than the A aggregates. At room temperature, the
      condensation rate of A with M-leading to the 'superaggregated' form A(t)-was
      slower and depended on the concentration of M. The superaggregated species A(t)
      was shown to be the most chemically stable species. Physico-chemical properties
      of these superaggregates are discussed as a potential new solution to improve the
      therapeutic efficacy of AmB.

PMID- 17029865
TI  - Voluntary counseling and testing among post-partum women in Botswana.
AB  - OBJECTIVE: To determine uptake and socio-demographics predictors of acceptance of
      voluntary counseling and testing (VCT) among post-partum women in Botswana.
      METHODS: Women attending maternal and child health clinics for their first post
      partum or well baby visit in three sites in Botswana were offered VCT after a
      written informed consent. A standardized questionnaire was used to collect socio
      demographic characteristics and reasons for declining VCT. RESULTS: From March
      1999 to November 2000, we approached 1735 post-partum women. Only 937 (54%) of
      those approached accepted VCT. In multiple logistic regression analysis, younger
      maternal age, not being married, and less formal education were significant
      predictors of acceptance of VCT. Thirty percent of women who accepted VCT were
      HIV-positive. CONCLUSION: Our results indicated that in Botswana prior to the
      initiation of a government Mother to Child Transmission (MTCT) prevention
      program, younger, unmarried, and less educated post-partum women were more likely
      to undergo VCT. PRACTICE IMPLICATIONS: Our results have shown that interventions
      to improve VCT among post-partum women and more generally among women of
      reproductive age are warranted in Botswana. These interventions should account
      for differences such age, marital status, education, and partner involvement to
      maximize VCT uptake.

PMID- 17029867
TI  - Complex intracellular calcium oscillations. A theoretical exploration of possible
      mechanisms.
AB  - Intracellular Ca(2+) oscillations are commonly observed in a large number of cell
      types in response to stimulation by an extracellular agonist. In most cell types
      the mechanism of regular spiking is well understood and models based on Ca(2+)
      induced Ca(2+) release (CICR) can account for many experimental observations.
      However, cells do not always exhibit simple Ca(2+) oscillations. In response to
      given agonists, some cells show more complex behaviour in the form of bursting,
      i.e. trains of Ca(2+) spikes separated by silent phases. Here we develop several
      theoretical models, based on physiologically plausible assumptions, that could
      account for complex intracellular Ca(2+) oscillations. The models are all based
      on one- or two-pool models based on CICR. We extend these models by (i)
      considering the inhibition of the Ca(2+)-release channel on a unique
      intracellular store at high cytosolic Ca(2+) concentrations, (ii) taking into
      account the Ca(2+)-activated degradation of inositol 1,4,5-trisphosphate (IP(3)),
      or (iii) considering explicity the evolution of the Ca(2+) concentration in two
      different pools, one sensitive and the other one insensitive to IP(3). Besides
      simple periodic oscillations, these three models can all account for more complex
      oscillatory behaviour in the form of bursting. Moreover, the model that takes the
      kinetics of IP(3) into account shows chaotic behaviour.

PMID- 17029868
TI  - Visualization of the chromosome scaffold and intermediates of loop domain
      compaction in extracted mitotic cells.
AB  - A novel extraction protocol for cells cultured on coverslips is described.
      Observations of the extraction process in a perfusion chamber reveal that cells
      of all mitotic stages are not detached from coverslips during extraction, and all
      stages can be recognized using phase contrast images. We studied the extracted
      cell morphology and distribution of a major scaffold component - topoisomerase
      IIalpha, in extracted metaphase and anaphase cells. An extraction using 2M NaCl
      leads to destruction of chromosomes at the light microscope level. Immunogold
      studies demonstrate that the only residual structure observed is an axial
      chromosome scaffold that contains topoisomerase IIalpha. In contrast, mitotic
      chromosomes are swelled only partially after an extraction using dextran sulphate
      and heparin, and it appears that this treatment does not lead to total
      destruction of loop domains. In this case, the chromosome scaffold and numerous
      structures resembling small rosettes are revealed inside extracted cells. The
      rosettes observed condense after addition of Mg2+-ions and do not contain
      topoisomerase IIalpha suggesting that these structures correspond to
      intermediates of loop domain compaction. We propose a model of chromosome
      structure in which the loop domains are condensed into highly regular structures
      with rosette organization.

PMID- 17029869
TI  - Patients' attitudes to totally implantable venous access port systems for
      gynecological or breast malignancies.
AB  - AIMS: The aim of this study was to analyze patients' port-related quality of
      life. PATIENTS AND METHODS: 260 consecutive patients with gynecological or breast
      malignancies were asked to take part in a questionnaire-based survey including 26
      questions, and 232 women agreed to participate in the study. The questionnaire
      inquired about port-related aspects of everyday life and the use of a central
      venous access port device for chemotherapy and supportive cancer care.
      Multivariate analysis was used to identify parameters associated with
      satisfaction and dissatisfaction in relation to the port. RESULTS: Most of the
      women were very satisfied with the use of a port to provide venous access for
      chemotherapy and supportive cancer care. Faster hospital procedures, good
      cosmetic results, and the ability to cope with the social environment had a
      significant influence on the degree of satisfaction. Fear of port punctures,
      inconvenient heparinization of the port, and fear of complications were found to
      be negative variables associated with the method. CONCLUSIONS: Port catheters are
      well accepted by patients for chemotherapy and supportive cancer care. Generally
      ports should be rapidly removed after the end of antineoplastic treatment in
      order to improve patients' satisfaction with the procedure.

PMID- 17029871
TI  - Re: Manfred Eigen's 70th birthday.

PMID- 17029870
TI  - Androgens' performance-enhancing effects in the inhibitory avoidance and water
      maze tasks may involve actions at intracellular androgen receptors in the dorsal
      hippocampus.
AB  - Androgens can have performance-enhancing effects in some cognitive tasks, but the
      mechanism of these effects has not been established. Experiments examined whether
      androgens' actions to bind to intracellular androgen receptors (ARs) in the
      hippocampus are necessary to enhance cognitive performance in the inhibitory
      avoidance and water maze tasks. If androgens' binding at ARs are essential, then
      blocking them through intrahippocampal administration of flutamide, an AR
      receptor antagonist, should attenuate androgens' performance-enhancing effects in
      the inhibitory avoidance and water maze tasks. In Experiments 1 and 2, flutamide
      was administered through intrahippocampal inserts to intact male rats immediately
      pre- and post-training in the inhibitory avoidance and water maze tasks. Both pre
      and post-training administration of flutamide to the dorsal hippocampus, but not
      missed sites, produced significantly poorer performance in the inhibitory
      avoidance and water maze tasks, without influencing control measures such as
      flinch/jump threshold or swim speed. In Experiment 3, flutamide administration to
      the hippocampus was delayed two hours following training in the inhibitory
      avoidance and water maze tasks. There was no significant effect of delayed
      administration of flutamide on performance in either of these tasks. Together,
      these findings suggest that blocking ARs in the dorsal hippocampus with flutamide
      administration immediately pre- or post-training can produce decrements in
      cognitive performance, which implies that androgens' performance-enhancing
      effects may occur, in part, through binding at intracellular androgen receptors
      in the dorsal hippocampus.

PMID- 17029872
TI  - To Manfred Eigen on his 70th birthday.

PMID- 17029873
TI  - Genotypes with phenotypes: adventures in an RNA toy world.
AB  - Evolution has created the complexity of the animate world and deciphering the
      language of evolution is the key towards understanding nature. The dynamics of
      evolution is simplified by considering it as a superposition of three less
      sophisticated processes: population dynamics, population support dynamics, and
      genotype-phenotype mapping. Evolution of molecules in laboratory assays provides
      a sufficiently simple system for the quantitative analysis of the three
      phenomena. Coarse-grained notions of structures like RNA secondary structures are
      used as model phenotypes. They provide an excellent tool for a comprehensive
      analysis of the entire complex of molecular evolution. The mapping from RNA
      genotypes into secondary structures is highly redundant. In order to find at
      least one sequence for every common structures one need only search a
      (relatively) small part of sequence space. The existence of selectively neutral
      phenotypes plays an important role for the the success and the efficiency of
      evolutionary optimization. Molecular evolution found a highly promising
      technological application in the design of biomolecules with predefined
      properties.

PMID- 17029874
TI  - On the generation of information as motive power for molecular evolution.
AB  - Molecular evolution can be described as a learning process during which
      previously inanimate matter developed the ability to organize all the reaction
      pathways that establish a living system. Common to all natural self-organizing
      procedures is the ability of matter to store, process and evaluate the
      information achieved by learning. Genetic information which is stored in RNA or
      DNA is the object of natural evolution. With the recognition of nature's
      concepts, evolutionary optimization was applied to biopolymers that are not
      optimally adapted for particular technical or medical purposes. Information can
      also be stored in molecules with structures and chemical properties that are
      completely different from nucleic acids. Therefore, optimization processes that
      mimic the natural evolutionary strategies can also be applied to small organic
      molecules. Much effort has been made theoretically and practically to find a
      certain optimized species within the (hyper)astronomical number of possible
      sequence alternatives. From a series of computer experiments it can be concluded
      that it is not necessary to search the entire sequence space in order to find a
      particular structure; this is advantageous because the diversity of mutant
      libraries that can realistically be achieved in the laboratory never extends to
      the number of theoretically possible sequences. Molecular mutant libraries that
      serve as starting populations for in vitro selection have been constructed for
      nucleic acids, proteins, peptides and small organic molecules.

PMID- 17029875
TI  - The role of peptide modules in protein evolution.
AB  - Protein evolution shows interesting strategies to be used in protein design.
      During evolution the creation of new proteins has been accomplished by combining
      different peptide modules, i.e. evolutionary successful stable folding units.
      Thereby, the evolution of proteins has been greatly enhanced. Today this
      mechanism of recombining optimized building blocks to design new proteins has
      been introduced into applied molecular evolution.

PMID- 17029876
TI  - Confocal spectroscopy in microstructures.
AB  - Confocal instrumentation makes it possible to carry out spectroscopic
      measurements with a very high signal-to-background ratio. The transit of a single
      fluorescent molecule through the focal point of the light can be monitored with
      this method. The particle transport can be observed in transparent microchannels.
      Examples of fluorescence correlation spectroscopy and single molecule handling in
      microstructures are discussed.

PMID- 17029877
TI  - Macrodipoles. Unusual electric properties of biological macromolecules.
AB  - The wide range of different effects induced by electric fields in biological
      macromolecules is clearly due to the unusual quality and quantity of their
      electric parameters. A general concept for a quantitative description of the
      polarizability of macromolecules remains to be established. In the case of DNA,
      experimental data indicate the existence of an effective polarization length
      N(p); at chain lengths N < N(p) the polarizability increases with N(2), whereas
      saturation is approached at N > or = N(p). The polarization length decreases with
      increasing ionic strength in close analogy to the Debye length, but is
      approximately 10 times larger than the Debye length. The dynamics of DNA
      polarization at high field strengths has been observed in the ns time range and
      is consistent with biased field induced ion dissociation. In the range of chain
      lengths from approximately 400 to approximately 850 base pairs DNA molecules
      exhibit permanent dipole moments, which are in a preferentially perpendicular
      direction to the end-to-end-vector, leading to a positive electric dichroism.
      These results are consistent with a "frozen" ensemble of bent DNA configurations
      and provide evidence for the existence of slow, non-elastic bending transitions.
      The electric parameters of proteins are usually dominated by a permanent
      anisotropy of the charge distribution, corresponding to permanent dipole moments
      of the order of several hundred Debye up to about 1500 Debye. Relatively small
      dipole moments of protein monomers add up to millions of Debye, when these
      proteins are in a vectorial organization in membrane patches, as found for
      bacteriorhodopsin and Na (+)K (+)-ATPase . In these cases the dipole vector may
      support vectorial ion transport. It is remarkable that the dipole moments of
      proteins usually show a relatively small dependence on the salt concentration; a
      rational for these observations is provided by a dipole potential at the plane of
      shear for rotational diffusion, which is defined in close analogy to the zeta
      potential for translational diffusion. Symmetry breaking leading to huge electric
      dipole moments may be expected for mixed lipid vesicles: according to model
      calculations the phase separation of lipid components with and without net
      charges may lead to very high dipole moments; the expectation has been verified
      experimentally for vesicles containing DMPA and DMPC. The state of these systems
      should be extremely sensitive to electric fields. In summary, there is an unusual
      wide variation of electric parameters associated with biological macromolecules
      and with biomolecular assemblies, which is the basis for the complexity of
      different phenomena induced by electric fields in biological systems.

PMID- 17029879
TI  - The saphenous veins--great and small or long and short?

PMID- 17029878
TI  - Practical PCR tools for the delineation of Contracaecum rudolphii A and
      Contracaecum rudolphii B (Ascaridoidea: Anisakidae) using genetic markers in
      nuclear ribosomal DNA.
AB  - Using genetic markers defined previously in the internal transcribed spacers (ITS
      1 and ITS-2) of nuclear ribosomal DNA (rDNA), PCR-coupled restriction fragment
      length polymorphism (PCR-RFLP) and specific PCR assays were established for the
      specific detection of each of two morphologically indistinguishable operational
      taxonomic units (Contracaecum rudolphii A and Contracaecum rudolphii B) within
      Contracaecum rudolphii (s.l.) and their differentiation from Contracaecum
      septentrionale, a closely related congener. Application of these tools to C.
      rudolphii (s.l.) adults from Phalacrocorax carbo sinensis (the Eurasian
      subspecies of the great cormorant) from Qinghai Lake in China, revealed C.
      rudolphii B to infect this host. This is the first report of C. rudolphii B in P.
      carbo sinensis outside of Europe (where it was originally detected), supporting
      the proposal that this species has a broad geographical distribution. Together
      with other methods, each of these molecular tools will be useful for
      investigating the ecology of C. rudolphii A and C. rudolphii B as well as C.
      septentrionale.

PMID- 17029880
TI  - Colony-stimulating factors in veterinary medicine: an unexplored potential.

PMID- 17029881
TI  - Stable concurrent synchronization in dynamic system networks.
AB  - In a network of dynamical systems, concurrent synchronization is a regime where
      multiple groups of fully synchronized elements coexist. In the brain, concurrent
      synchronization may occur at several scales, with multiple "rhythms" interacting
      and functional assemblies combining neural oscillators of many different types.
      Mathematically, stable concurrent synchronization corresponds to convergence to a
      flow-invariant linear subspace of the global state space. We derive a general
      condition for such convergence to occur globally and exponentially. We also show
      that, under mild conditions, global convergence to a concurrently synchronized
      regime is preserved under basic system combinations such as negative feedback or
      hierarchies, so that stable concurrently synchronized aggregates of arbitrary
      size can be constructed. Robustnesss of stable concurrent synchronization to
      variations in individual dynamics is also quantified. Simple applications of
      these results to classical questions in systems neuroscience and robotics are
      discussed.

PMID- 17029883
TI  - Use of multi-coil parallel-gap resonators for co-registration EPR/NMR imaging.
AB  - This article reports experimental investigations on the use of RF resonators for
      continuous-wave electron paramagnetic resonance (cw-EPR) and proton nuclear
      magnetic resonance (NMR) imaging. We developed a composite resonator system with
      multi-coil parallel-gap resonators for co-registration EPR/NMR imaging. The
      resonance frequencies of each resonator were 21.8MHz for NMR and 670MHz for EPR.
      A smaller resonator (22mm in diameter) for use in EPR was placed coaxially in a
      larger resonator (40mm in diameter) for use in NMR. RF magnetic fields in the
      composite resonator system were visualized by measuring a homogeneous 4-hydroxy
      2,2,6,6-tetramethyl-piperidinooxy (4-hydroxy-TEMPO) solution in a test tube. A
      phantom of five tubes containing distilled water and 4-hydroxy-TEMPO solution was
      also measured to demonstrate the potential usefulness of this composite resonator
      system in biomedical science. An image of unpaired electrons was obtained for 4
      hydroxy-TEMPO in three tubes, and was successfully mapped on the proton image for
      five tubes. Technical problems in the implementation of a composite resonator
      system are discussed with regard to co-registration EPR/NMR imaging for animal
      experiments.

PMID- 17029884
TI  - 13C/14N heteronuclear multiple-quantum correlation with rotary resonance and
      REDOR dipolar recoupling.
AB  - A two-dimensional (13)C/(14)N heteronuclear multiple quantum correlation (HMQC)
      experiment using dipolar recoupling under magic-angle spinning (MAS) is
      described. The experiment is an extension of the recent indirect (13)C detection
      scheme for measuring (14)N quadrupolar coupling under MAS. The recoupling allows
      the direct use of the much larger dipolar interaction instead of the small J and
      residual dipolar couplings for establishing (13)C/(14)N correlations. Two
      recoupling methods are incorporated into the HMQC sequence, both applying rf only
      to the observed (13)C spin. The first one uses the REDOR sequence with two pi
      pulses per rotor cycle. The second one uses a cw rf field matching the spinning
      frequency, known as rotary resonance. The effects of CSA, T(2)(') signal loss,
      MAS frequency and stability and t(1)-noise are compared and discussed.

PMID- 17029886
TI  - Elevated serum B-Lymphocyte activating factor (BAFF) in chronic hepatitis C virus
      infection: association with autoimmunity.
AB  - In this study we aimed to determine whether serum B-lymphocyte activating factor
      (BAFF) level is increased in patients with chronic hepatitis C virus (HCV)
      infection, and to assess its association with HCV-related autoimmunity. Sixty
      five patients with chronic HCV infection were compared with two disease control
      groups [57 patients with systemic lupus erythematosus (SLE) and 15 with chronic
      hepatitis B virus (HBV) infection] and a healthy control group of 35 individuals.
      A special attention was given to HCV-related arthralgia and or vasculitis. Serum
      BAFF was assessed in all studied individuals, whereas rheumatoid factor (RF),
      anti-cardiolipin antibodies (aCL), and cryoglobulins were determined in HCV and
      HBV infected patients, and anti-dsDNA antibodies and aCL were assessed in
      patients with SLE. Mean serum BAFF was increased in patients with HCV infection
      and SLE (2.4+/-0.8 ng/ml and 3.1+/-1.34 ng/ml respectively) compared to 1.1+/
      0.14 ng/ml in patients with HBV; and to 1.1+/-0.27 in healthy controls (all,
      p<0.0001). The elevation in serum BAFF was associated with HCV-related arthralgia
      and or vasculitis (p<0.0001), and with the presence of aCL and of cryoglobulins.
      HBV patients lacked features suggestive of autoimmunity. In SLE patients,
      elevated serum BAFF was in association with the presence of anti-dsDNA (p=0.002).
      As in other autoimmune diseases, increased serum BAFF was also found in patients
      with chronic HCV infection. Elevated serum BAFF levels were associated with
      clinical and laboratory features of autoimmunity, suggesting that BAFF may play a
      role in HCV-related autoimmunity.

PMID- 17029885
TI  - Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin
      deficiencies in monozygotic twins discordant for type 1 diabetes.
AB  - Incomplete intrinsic penetrance is the failure of some genetically susceptible
      individuals (e.g., monozygotic twins of those who have a trait) to exhibit that
      trait. For the first time, we examine penetrance of susceptibility genes for
      multiple MHC gene-determined traits in the same subjects. Serum levels of IgA,
      IgD, IgG3, but not IgG4, in 50 pairs of monozygotic twins discordant for type 1
      diabetes (T1D) correlated more closely in the twins than in random paired
      controls. The frequencies of subjects deficient in IgA (6%), IgD (33%) and IgG4
      (12%), but not in IgG3, were higher in the twins than in controls. We postulate
      that this was because the MHC haplotypes (and possible non-MHC genes) that
      predispose to T1D also carry susceptibility genes for certain immunoglobulin
      deficiencies. Immunoglobulin deficiencies were not associated with T1D. Pairwise
      concordance for the deficiencies in the twins was 50% for IgA, 57% for IgD and
      50% for IgG4. There were no significant associations among the specific
      immunoglobulin deficiencies except that all IgA-deficient subjects had IgD
      deficiency. Thus, intrinsic penetrance is a random process independently
      affecting different MHC susceptibility genes. Because multiple different external
      triggers would be required to explain the results, differential environmental
      determinants appear unlikely.

PMID- 17029887
TI  - Evaluation of intrinsic chemical kinetics and transient product spectra from time
      resolved spectroscopic data.
AB  - This communication is devoted to the evaluation of true spectra and intrinsic
      (microscopic) rate constants from apparent kinetics measured in time-resolved
      spectroscopic experiments monitoring complex relaxation dynamics of multi
      intermediate systems. Retinal proteins, cytochrom c oxidase, phytochrome,
      hemoglobin, and photoactive yellow protein are examples of natural systems in
      which several transient states (intermediates) overlap so strongly, both in time
      and spectral domains, that their isolation and full characterization by classical
      biochemical methods is impossible, and mathematical evaluation of their true
      spectra and microscopic kinetic constants is required. Most of the popular
      methods for analysis of kinetic data, global fitting (GF), singular value
      decomposition (SVD), principal component analysis (PCA) and factor analysis (FA),
      are applicable to two-dimensional (2D, in time and spectral domains) arrays of
      data. All these methods produce only a phenomenological description of data, that
      approximates the measured data only with apparent kinetics. A fundamental
      limitation, namely, insufficient information in 2D data, does not allow any of
      these methods to reach the final goal: to recalculate from apparent to intrinsic
      values in any but the most trivial cases. A strategy was proposed (J.F. Nagle,
      Biophys. J.. 59 (1991) 476-487) to include an additional (third) information-rich
      dimension, temperature, into the simultaneous computer analysis. A simultaneous
      direct fitting of 3D data arrays to systems of differential rate equations allows
      recalculation of apparent kinetics into true spectra and intrinsic rate
      constants. In spite of its evident theoretical advantages, this strategy has not
      been successful on real data. Here we describe another custom-built program,
      SCHEMEFIT, developed for the same purpose: to fit measured kinetics directly to
      the system of coupled differential rate equations describing the photochrome's
      relaxation dynamics. Though sharing the main strategy with the previous approach,
      SCHEMEFIT is based on a different set of numeric algorithms, and its application
      requires different tactics. Its performance is illustrated on synthetic data, and
      compared with GF and SVD. An example of applying SCHEMEFIT to the photocycle of
      halorhodopsin is also reported.

PMID- 17029888
TI  - The self-association of flavin mononucleotide (FMN(2-)) as determined by (1)H NMR
      shift measurements.
AB  - The concentration dependence of the (1)H NMR chemical upfield shifts of the
      protons H6, H9, H7alpha, and H8alpha of the 7,8-dimethylisoalloxazine residue of
      flavin mononucleotide (FMN(2-)) has been measured and the self-stacking tendency
      of FMN(2-) was quantified with the isodesmic model of indefinite non-cooperative
      self-association. The stacking tendency of FMN(2-) is considerable and described
      in the concentration range of 0.0025-0.1 M with the indicated model by K = 27 +/-
      15 M(-1) (25 degrees C; I = 0.1-0.3 M). This result is compared with related ones
      from the literature. The caveats regarding the self-stacking properties of FMN(2
      ) and their dependence on the concentration are discussed.

PMID- 17029889
TI  - Self-sustained pH oscillations in a compartmentalized enzyme reactor system.
AB  - This work represents our continued effort toward fulfilling the need to discover
      a model system for experimental investigations of temporal oscillations in an
      enzyme-membrane system. In this paper, the regions in the parameter space where
      self-sustained pH oscillations can be induced for a compartmentalized enzyme
      reactor system, which consists of a well-stirred reactor, a reservoir and a
      membrane containing no enzyme, were determined via numerical simulation with two
      proteolytic enzymes: papain (EC 3.4.22.2) and alpha-chymotrypsin (EC 3.4.21.1).
      The sizes of the regions were qualitatively compared with those associated with
      enzymic membrane system. As a result, we found that the possibility of
      experimentally observing self-sustained oscillations in the compartmentalized
      papain reactor system, as well as in the papain-membrane system, is high.
      However, self-sustained pH oscillations are less likely in the compartmentalized
      alpha-chymotrypsin reactor system than in the alpha-chymotrypsin-membrane system.

PMID- 17029890
TI  - Evidence for increased proton dissociation in low-activity forms of
      dephosphorylated squash-leaf nitrate reductase.
AB  - The pH dependence of squash-leaf nitrate reductase has been studied. It has been
      found that high- and low-activity forms of purified nitrate reductase (both forms
      dephosphorylated) have different optimum pH values. A high-activity form has
      always a higher pH optimum compared with a low-activity form. Model computations
      show that the decrease in activity and the corresponding change of the pH optimum
      is apparently due to a conformation-dependent increase of proton dissociation of
      the enzyme. As previously shown, this behavior is also observed in leaf extracts
      during the conversion (and probably phosphorylation of nitrate reductase) from a
      high-active form to a low-active form when plants are transferred from light to
      darkness.

PMID- 17029891
TI  - Electrostatic contribution to the bending of DNA.
AB  - A model is derived that accounts for the short-range electrostatic contribution
      to the bending of DNA molecule in solution and in complexes with proteins in
      terms of the non-linear Poisson-Boltzmann equation. We defined that the short
      range electrostatic interactions depend on the changes of the polyion surface
      charge density under deformation, while the long-range interactions depend on the
      bending-induced changes in distances between each two points along the polyion
      axis. After an appropriate simplification of the Poisson-Boltzmann equation, the
      short-range term is calculated separately giving the lower limit for the
      electrostatic contribution to the DNA persistence length. The result is compared
      with the theoretical approaches developed earlier [M. Fixman, J. Chem. Phys. 76
      (1982) 6346; M. Le Bret, J. Chem. Phys. 76 (1982) 6243] and with the experimental
      data. The conclusion is made that the results of Fixman-Le Bret, which took into
      account both types of the electrostatic interactions for a uniformly bent
      polyion, give the upper limit for the electrostatic persistence length at low
      ionic strength, and the actual behavior of the DNA persistence length lies
      between two theoretical limits. Only the short-range term is significant at
      moderate-to-high ionic strength where our results coincide with the predictions
      of Fixman-Le Bret. The bending of DNA on the protein surface that is accompanied
      by an asymmetric neutralization of the DNA charge is also analyzed. In this case,
      the electrostatic bending energy gives a significant favorite contribution to the
      total bending energy of DNA. Important implications to the mechanisms of DNA
      protein interactions, particularly in the nucleosome particle, are discussed.

PMID- 17029892
TI  - Activity coefficients of the electrolyte and the amino acid in water + NaNO(3) +
      glycine and water + NaCl + DL-methionine systems at 298.15 K.
AB  - The activity coefficients at 298.15 K of glycine in water + NaNO(3) + glycine
      system and dl-methionine in water + NaCl + dl-methionine system are reported. The
      measurements were performed in an electrochemical cell with two ion selective
      electrodes, a cation and an anion ion selective electrode, each versus a double
      junction reference electrode. The concentrations of the electrolytes and the
      amino acids studied covered up to 1.0 molality electrolyte, 2.4 molality glycine
      and 0.2 molality dl-methionine. The results of the activity coefficients of
      glycine are compared with the activity coefficients of glycine in water + NaCl +
      glycine and water + KCl + glycine systems, obtained from the previous studies.
      The results show that the nature of both the cation and the anion of an
      electrolyte have significant effects on the activity coefficient of glycine in
      aqueous electrolyte solutions. The results also show that there are attractive
      interactions between the molecules of glycine and NaNO(3) and repulsive
      interactions between the molecules of dl-methionine and NaCl.

PMID- 17029893
TI  - Length dependence of displacement fluctuations and velocity in microtubule
      sliding movement driven by sea urchin sperm outer arm beta dynein in vitro.
AB  - We have studied the dependence on microtubule length of sliding velocity and
      positional fluctuation from recorded trajectories of microtubules sliding over
      sea urchin sperm outer arm beta dynein in a motility assay in vitro. The
      positional fluctuation was quantified by calculating the mean-square displacement
      deviation from the average, the calculation of which yields an effective
      diffusion coefficient. We have found that (1) the sliding velocity depends
      hyperbolically on the microtubule length, and (2) the effective diffusion
      coefficients do not depend on the length for sufficiently long microtubules. The
      length dependence of the sliding velocity indicates that the duty ratio, defined
      as the force producing period over the total cycle time of beta dynein
      interaction with microtubule, is very small. The length independence of the
      effective diffusion coefficient indicates that there is a correlation in the
      sliding movement fluctuation of microtubules.

PMID- 17029894
TI  - Biphasic transitions of a hairpin hexanucleotide triplex DNA.
AB  - The conformational transitions (helix-coil transitions) of three hairpin triple
      helices, models 5'-(A-G)(3) + 5'-(T-C)(3)-T(4)-((br)C-T)(3) [CY], 5'-(A-G)(3) +
      5'-(T-(br)C)(3)-T(4)-(C-T)(3) [YC] and 5'-(A-G)(3) + 5'-(T-(br)C)(3)-T(4)-((br)C
      T)(3) [YY], are characterized in this work by UV spectroscopy. Melting of these
      triplexes is biphasic, and the profiles are used to obtain the thermodynamic
      parameters. The thermodynamic properties of the hairpin triplex are T(m) = 19.45
      degrees C and DeltaH(vH) = 293.12 kJ mol(-1) for CY, T(m) = 22.85 degrees C and
      DeltaH(vH) = 256.63 kJ mol(-1) for YC and T(m) = 28.47 degrees C and DeltaH(vH) =
      234.68 kJ mol(-1) for YY at pH 4.4. Those of the duplex are T(m) = 30.50 degrees
      C and DeltaH(vH) = 427.09 kJ mol(-1) for CY, T(m) = 32.96 degrees C and
      DeltaH(vH) = 374.47 kJ mol(-1) for YC and T(m) = 33.24 degrees C and DeltaH(vH) =
      329.67 kJ mol(-1) for YY at pH 4.4. The distinct transitions of triplex to duplex
      and duplex to single strands are analyzed using the nearest-neighbor Ising model.
      Electrostatic effects on each conformation are also analyzed.

PMID- 17029895
TI  - Characterization of fluorescence quenching in bifluorophoric protease substrates.
AB  - NorFES is a relatively rigid, bent undecapeptide which contains an amino acid
      sequence that is recognized by the serine protease elastase (AspAlaIleProNle
      downward arrow SerIleProLysGlyTyr ( downward arrow indicates the primary cleavage
      site)). Covalent attachment of a fluorophore on each side of NorFES's elastase
      cleavage site enables one to use a change of fluorescence intensity as a measure
      of enzymatic activity. In this study two bichromophoric NorFES derivatives, D
      NorFES-A and D-NorFES-D, were prepared in which D (donor) was
      tetramethylrhodamine and A (acceptor) was rhodamine-X, two chromophores with
      characteristics suitable for energy transfer. Absorption and fluorescence spectra
      were obtained with both the intact and cleaved homodoubly, heterodoubly and
      singly labeled derivatives. It was found that both the homo and hetero doubly
      labeled derivatives form ground-state complexes which exhibit exciton bands. The
      hetero labeled derivative exhibits little or no resonance energy transfer.
      Spectral measurements were also done in urea, which partially disrupts ground
      state dimers.

PMID- 17029896
TI  - Interaction of a G-DNA quadruplex with mono- and divalent cations. A force field
      calculation.
AB  - The formation and stability of four-stranded DNA in solution is specifically
      dependent on the type of cations present. The interaction potential of a model
      quadruplex structure with different mono- and divalent ions was determined by
      force field calculations. Though the electrostatic contribution to the total
      energy is mainly responsible for the stabilisation of the cations within the
      quadruplex channel, it is the van der Waals interaction at short distances that
      determines the specific characteristics of the different cations. An explicit
      consideration of the solvent indicates that the position of water molecules in
      close proximity to the DNA channel have a strong influence on the form of the
      potential, and hence on the capability of the cations for leaving and re-entering
      the cavity. The effect of cation size, as expressed through their Lennard-Jones
      parameters, is discussed.

PMID- 17029897
TI  - Strong and weak binding of water to proteins studied by NMR triple-quantum
      filtered relaxation spectroscopy of (17)O-water.
AB  - The triple-quantum filtered (TQF) spin-echo signal of (17)O-water, in the
      presence of proteins, was analysed to yield estimates of the number of weakly,
      and strongly bound water molecules. The analysis used a constrained direct
      iterative regression procedure with a three-state model of fast-exchange. Thus,
      the population size of free, weakly, and strongly bound water were determined
      simultaneously. The two fractions of the bound water were estimated by using
      correlation time(s) estimated in other studies. Bovine serum albumin (BSA), basic
      pancreatic trypsin inhibitor (BPTI), lysozyme and oxyhaemoglobin were studied. Of
      the four proteins, BSA contained the largest number of strongly and weakly bound
      water molecules, there being approximately 30 of the former and approximately
      3000 of the latter under conditions of high protein concentration. The
      correlation time of the proteins increases with their concentration in solution,
      and when this was taken into account for BSA the estimated number of strongly
      bound water molecules did not change significantly. This NMR technique, and data
      analysis, will probably also be useful in studies of water binding and mobility
      in various systems including hydrogels, protein networks, membranes, cells and
      tissues.

PMID- 17029898
TI  - A quantitative analysis of single protein-ligand complex separation with the
      atomic force microscope.
AB  - Force measurements on and within single macromolecular complexes utilizing
      techniques such as atomic force microscopy, optical trapping, flexible glass
      fibers, and magnetic beads provide a rich source of quantitative data on
      biomolecular processes. Stochastic thermal fluctuations, an undesirable source of
      noise in macroscopic biochemical experiments, are an essential element of these
      sensitive and novel experiments. With the proper analysis, a great deal of
      information can be gleaned from measurements of these fluctuations. A
      quantitative framework for analyzing such measurements, based on Kramers' theory
      of molecular dissociation, is developed. The analysis reveals the kinetic origin
      and stochastic nature of the measurements. This framework is presented in the
      context of protein-ligand separation with the atomic force microscope.

PMID- 17029899
TI  - Free energy of the binding of uridylic acid oligomers with double stranded
      poly(A) x poly(U).
AB  - The binding parameters (K, omega) and the free energy (DeltaG(0)) of triple helix
      formation have been estimated for complexes of oligo(U)(n) (n = 5, 7-10) with
      poly(A) . poly(U) on the basis of hypochromicity measurements. The data were
      treated according to the formula of McGhee and von Hippel [J. Mol. Biol. 86
      (1974) 469] by a computer program ALAU [H. Schutz et al., Stud. Biophys. 104
      (1984) 23] which takes absorbancies and total concentrations as input. In 1 mM
      cacodylate buffer pH 7.0 with 10 mM NaCl and 10 mM MgCl(2) at 5 degrees C the
      free energy of contiguous binding was found to be a linear function of the
      oligomer length with a slope of DeltaG(c,U)(0) = -0.72 (+/-0.03) kcal x mol(-1)
      per nucleotide. The mean cooperativity coefficient (omega) was 24.5 (+/- 5.6),
      and the corresponding free energy of interaction between the neighbouring
      oligonucleotides in the third strand was DeltaG(0(omega)) = -1.74 (+/-0.13) kcal
      x mol(-1).

PMID- 17029900
TI  - A simple theory of motor protein kinetics and energetics.
AB  - A simple stochastic theory for kinetics and energetics of the movement of single
      motor proteins is presented. The model combines the biochemical cycle of
      nucleotide hydrolysis with the motor protein translocation. Based on the theory
      of Markov processes, the model provides the force-velocity relationship, the
      isometric force, and the stochastic stepping of the motor protein along its one
      dimensional track. The theoretical model provides a conceptual framework for
      realistic studies of motor proteins. Relationship between the present theory and
      other existing models is discussed.

PMID- 17029901
TI  - Repair effect of phenylpropanoid glycosides on thymine radical anion induced by
      pulse radiolysis.
AB  - Repair effects on thymine radical anion by six phenylpropanoid glycosides (PPGs),
      isolated from Pedicularis species, were studied using pulse radiolysis method.
      The thymine radical anion was produced by the reaction of hydrated electron with
      thymine. PPGs were added into the thymine solution saturated with N(2). Kinetic
      analysis showed that transient absorption spectrum of thymine radical anion
      formed at first, and then after several microseconds of pulse radiolysis changed
      to that of PPG radical anion. The evidence indicated that thymine radical anion
      was repaired through one-electron transfer between the radical anion and PPG.
      Electrophilic phenyl-substituted unsaturated carboxylic group containing in PPGs'
      structure was able to capture electron from thymine radical anion before it
      undergo reversible protonation. The reaction rate constants of electron transfer
      from thymine radical anion to PPGs were within 1.16-2.29 x 10(9) dm(3) mol(-1) s(
      1).

PMID- 17029902
TI  - Production of soybean isoflavone genistein in non-legume plants via genetically
      modified secondary metabolism pathway.
AB  - Genetic modification of secondary metabolic pathways to produce desirable natural
      products is an attractive approach in plant biotechnology. In our study, we
      attempted to produce a typical soybean isoflavone genistein, a well-known health
      promoting metabolite, in non-legume plants via genetic engineering. Both
      overexpression and antisense suppression strategies were used to manipulate the
      expression of several genes encoding key enzymes in the flavonoids/isoflavonoids
      pathway in transgenic tobacco, lettuce, and petunia. Introducing soybean
      isoflavone synthase (IFS) into these plants, which naturally do not produce
      isoflavonoids due to a lack of this leguminous enzyme, resulted in genistein
      biosynthesis in tobacco petals, petunia leaves and petals, and lettuce leaves. In
      tobacco, when flavanone 3-hydroxylase (F3H) expression was suppressed by its
      antisense gene while soybean IFS was overexpressed at the same time, genistein
      yield increased prominently. In addition, overexpression of phenylalanine ammonia
      lyase (PAL) also led to an enhanced genistein production in tobacco petals and
      lettuce leaves in the presence of IFS than in the plants that overexpressed only
      IFS.

PMID- 17029903
TI  - Methodology for adding glycemic index and glycemic load values to 24-hour dietary
      recall database.
AB  - OBJECTIVES: We describe a method of adding the glycemic index (GI) and glycemic
      load (GL) values to the nutrient database of the 24-hour dietary recall interview
      (24HR), a widely used dietary assessment. We also calculated daily GI and GL
      values from the 24HR. METHODS: Subjects were 641 healthy adults from central
      Massachusetts who completed 9067 24HRs. The 24HR-derived food data were matched
      to the International Table of Glycemic Index and Glycemic Load Values. The GI
      values for specific foods not in the table were estimated against similar foods
      according to physical and chemical factors that determine GI. Mixed foods were
      disaggregated into individual ingredients. RESULTS: Of 1261 carbohydrate
      containing foods in the database, GI values of 602 foods were obtained from a
      direct match (47.7%), accounting for 22.36% of dietary carbohydrate. GI values
      from 656 foods (52.1%) were estimated, contributing to 77.64% of dietary
      carbohydrate. The GI values from three unknown foods (0.2%) could not be
      assigned. The average daily GI was 84 (SD 5.1, white bread as referent) and the
      average GL was 196 (SD 63). CONCLUSION: Using this methodology for adding GI and
      GL values to nutrient databases, it is possible to assess associations between GI
      and/or GL and body weight and chronic disease outcomes (diabetes, cancer, heart
      disease). This method can be used in clinical and survey research settings where
      24HRs are a practical means for assessing diet. The implications for using this
      methodology compel a broader evaluation of diet with disease outcomes.

PMID- 17029904
TI  - Gender difference in the effect of intrauterine malnutrition on the central
      anorexigenic action of insulin in adult rats.
AB  - OBJECTIVE: We evaluated whether insulin hypophagia and hypothalamic signaling are
      affected in adult rats exposed to intrauterine undernutrition. METHODS: Pregnant
      rats ate ad libitum throughout pregnancy and lactation (control, C) or 50% of
      control intake in the first 2 wk of pregnancy (restricted, R). Four-month-old C
      and R progeny received insulin or vehicle intracerebroventricular injections for
      evaluation of 24-h food intake, hypothalamic insulin receptor (IR), and IR
      substrate-1 (IRS-1) protein content and tyrosine phosphorylation, pp185
      phosphorylation, and IRS-1 association with phosphatidylinositol 3-kinase (PI3
      K). RESULTS: With respect to males, R males had normal body composition and
      insulin-induced hypophagia. IR protein levels were lower but IR phosphorylation
      was higher in R than in C males. IRS-1 levels and phosphorylation were similar
      between C and R males, insulin stimulated an IRS-1/PI3-K association in C but not
      in R males, and pp185 phosphorylation was higher in R than in C males. For
      females, body fat and serum leptin were elevated in R females. Insulin inhibited
      food intake in C but not in R females. Insulin-induced IR phosphorylation and
      protein levels of IR and IRS-1 were higher in R than in C females. However, IRS-1
      and pp185 phosphorylation and IRS-1/PI3-K association were significantly
      stimulated by insulin in C but not in R females. CONCLUSIONS: Female adult rats
      exposed to intrauterine undernutrition had increased adiposity, marked impairment
      of hypothalamic insulin signaling, and loss of insulin-induced hypophagia. These
      disturbances were less severe or even absent in male progeny. The findings show
      that female progeny are more susceptible than their male siblings to the effects
      of maternal malnutrition.

PMID- 17029905
TI  - Nucleic acid structure and recognition.
AB  - We review the global structures adopted by branched nucleic acids, including
      three- and four-way helical junctions in DNA and RNA. We find that some general
      folding principles emerge. First, all the structures exhibit a tendency to
      undergo pairwise coaxial helical stacking when permitted by the local
      stereochemistry of strand exchange. Second, metal ions generally play an
      important role in facilitating folding of branched nucleic acids. These
      principles can be applied to functionally important branched nucleic acids, such
      as the Holliday DNA junction of genetic recombination, and the hammerhead
      ribozyme in RNA.

PMID- 17029906
TI  - Electron transfer and electronic energy relaxation under high hydrostatic
      pressure.
AB  - The following question has been addressed in the present work. How external high
      (up to 8 kbar) hydrostatic pressure acts on photoinduced intramolecular electron
      transfer and on exciton relaxation processes? Unlike phenomena, as they are, have
      been studied in different systems: electron transfer in an artificial Zn
      porphyrin-pyromellitimide (ZnP-PM) supramolecular electron donor-acceptor complex
      dissolved in toluene measured at room temperature; exciton relaxation in a
      natural photosynthetic antenna protein called FMO protein measured at low
      temperatures, between 4 and 100 K. Spectrally selective picosecond time-resolved
      emission technique has been used to detect pressure-induced changes in the
      systems. The following conclusions have been drawn from the electron transfer
      study: (i) External pressure may serve as a potential and sensitive tool not only
      to study, but also to control and tune elementary chemical reactions in solvents;
      (ii) Depending on the system parameters, pressure can both accelerate and inhibit
      electron transfer reactions; (iii) If competing pathways of the reaction are
      available, pressure can probably change the branching ratio between the pathways;
      (iv) The classical nonadiabatic electron transfer theory describes well the
      phenomena in the ZnP-PM complex, assuming that the driving force or/and
      reorganisation energy depend linearly on pressure; (v) A decrease in the ZnP-PM
      donor-acceptor distance under pressure exerts a minor effect on the electron
      transfer rate. The effect of pressure on the FMO protein exciton relaxation
      dynamics at low temperatures has been found marginal. This may probably be
      explained by a unique structure of the protein [D.E. Trondrud, M.F. Schmid, B.W.
      Matthews, J. Mol. Biol. 188 (1986) p. 443; Y.-F. Li, W. Zhou, E. Blankenship,
      J.P. Allen, J. Mol. Biol., submitted]. A barrel made of low compressibility beta
      sheets may, like a diving bell, effectively screen internal bacteriochlorophyll a
      molecules from external influence of high pressure. The origin of the observed
      slow pico = and subnanosecond dynamics of the excitons at the exciton band bottom
      remains open. The phenomenon may be due to weak coupling of phonons to the
      exciton states or/and to low density of the relevant low-frequency (
      approximately 50 cm(-1)) phonons. Exciton solvation in the surrounding protein
      and water-glycerol matrix may also contribute to this effect. Drastic changes of
      spectral, kinetic and dynamic properties have been observed due to protein
      denaturation, if the protein was compressed at room temperature and then cooled
      down, as compared to the samples, first cooled and then pressurised.

PMID- 17029907
TI  - Modern science and the explosion of new knowledge.
AB  - The technological evolution of mankind accelerated enormously after the
      institutionalization of science in the 19th century. In parallel with the vast
      number of beneficial effects derived from the scientific revolution, the
      explosion of new knowledge and its centralization in only a few countries has
      generated a number of complex situations that present major challenges for the
      modern science. These include the asymmetrical distribution in the planet of
      young people and science, the super-specialization derived from the information
      overload and the difficulties in teaching the vast amount of new knowledge
      generated each year by science.

PMID- 17029908
TI  - Biophysical properties of epithelial water channels.
AB  - The biophysical models describing the structure of water pores or channels have
      evolved, during the last forty years, from a pure 'black box' approach to a
      molecular based proposal. The initial 'sieving pore' in which water and other
      molecules were moving together was replaced by a more restrictive model, where
      water is moving alone in a 'single file' mode. Aquaporins discovery and cloning
      [G.M. Preston, T.P. Carroll, W.B. Guggino, P. Agre, Science 256 (1992) 365]
      leaded to the 'hour-glass model' and other alternative proposals, combining
      information coming from molecular biology experiments and two dimensional
      crystallography. Concerning water transfers in epithelial barriers the problem is
      quite complex, because there are at least two alternative pathways: paracellular
      and transcellular and three different driving forces: hydrostatic pressure,
      osmotic pressure or 'transport coupled' movements. In the case of ADH-sensitive
      epithelia it is more or less accepted that regulated water channels (AQP2), that
      can be inserted in the apical membrane, coexist with basolateral resident water
      channels (AQP3). The mechanism underlying the so-called 'transport associated
      water transfer' is still controversial. From the classical standing gradient
      model to the ion-water co-transport, different hypothesis are under
      consideration. Coming back to hormonal regulations, other than the well-known
      regulation by neuro-hypophysis peptides, a steroid second messenger,
      progesterone, has been recently proposed [P. Ford, G. Amodeo, C. Capurro, C.
      Ibarra, R. Dorr, P. Ripoche, M. Parisi, Am. J. Physiol. 270 (1996) F880].

PMID- 17029910
TI  - A re-analysis of the relationship among coping, symptom severity and quality of
      life in schizophrenia.

PMID- 17029909
TI  - Impaired verbal source monitoring in schizophrenia: an intermediate trait
      vulnerability marker?
AB  - Patients with schizophrenia, particularly those with positive symptoms show
      impaired verbal source monitoring. Specific cognitive deficits have been observed
      during both active and remission phases of the illness as well as in groups of
      unaffected first degree relatives of patients with schizophrenia. This type of
      schizophrenia vulnerability marker may precede the onset of frank psychotic
      symptoms and contribute to their developments. The aim of this study was first to
      determine if unaffected siblings were impaired in discriminate internal vs.
      external generated events when compared to their remitted schizophrenics
      relatives and healthy subjects. Performances of healthy subjects were then
      compared with results from previous studies with acute hallucinating patients,
      acute non-hallucinating patients and patients with resistant auditory verbal
      hallucinations. Compared with healthy subjects, unaffected siblings are impaired
      (effect size, ES=0.7), remitted or acute non-hallucinating patients are more
      impaired than siblings (ES=1.4); patients with verbal auditory hallucinations
      (acute or resistant) are even more impaired than non-hallucinating patients
      (ES=2.1). Our results suggest that a source monitoring deficit could be
      considered as an intermediate vulnerability marker of schizophrenia.

PMID- 17029911
TI  - STR loci D10S2325, D16S539 and D19S253: Northern Thai population data.
AB  - The STR loci D10S2325, D16S539 and D19S253 were analyzed in 203 unrelated
      Northern Thai. A power of discrimination of 0.954, 0.923 and 0.921 and a power of
      exclusion of 0.690, 0.542 and 0.632, respectively were found. The combined power
      of discrimination and exclusion reached 0.99972 and 0.9478, respectively. No
      deviation from the Hardy-Weinberg equilibrium was observed for the three loci.

PMID- 17029912
TI  - Amphetamine pretreatment accelerates the subsequent escalation of cocaine self
      administration behavior.
AB  - It has been proposed that some neuroadaptations that underlie behavioral
      sensitization may play a role in the development and persistence of addiction.
      However, whether or not sensitization facilitates the development of symptoms
      specific to addiction, such as the escalation of drug intake, is not known. We
      examined, therefore, the effect of pretreatment with a sensitizing regimen of
      amphetamine on the escalation of subsequent drug intake in rats given the
      opportunity to self-administer cocaine. Amphetamine pretreatment produced
      psychomotor sensitization and also accelerated the subsequent escalation of
      cocaine intake. This suggests that the neural circuits that are altered as a
      consequence of repeated amphetamine treatment, and the induction of
      sensitization, may overlap with those responsible for the development of some
      addiction-like behaviors.

PMID- 17029913
TI  - Association of the serotonin transporter promotor polymorphism with suicide
      attempters with a high medical damage.
AB  - Serotonergic neurotransmission has been implicated in suicidal behavior,
      including inconsistent results concerning the serotonin transporter promoter
      polymorphism (5-HTTLPR). Here, we analyzed the 5-HTTLPR in suicide attempters
      (n=85). Comparing the presence of SS with SL+LL genotypes showed a significantly
      higher prevalence of the SS genotype in suicide attempters with high medical
      damage scores (chi2=9.054, df=1, p=0.0026). The results suggest that the S-allele
      may predispose for suicidal behavior characterized by high determination.

PMID- 17029914
TI  - Molecular dynamics simulation of a dye molecule in the interior of a bilayer: 1,6
      diphenyl-1,3,5-hexatriene in dipalmitoylphosphatidylcholine.
AB  - A molecular dynamics simulation was carried out for a
      dipalmitoylphosphatidylcholine (DPPC) membrane in its liquid crystalline state
      containing different concentrations of the dye molecule 1,6-diphenyl-1,3,5
      hexatriene (DPH). From a numerical analysis of the trajectories, we obtained
      information concerning structural changes of the membrane due to the presence of
      the probe and some hydrodynamic information concerning the probe itself. The
      hydrodynamic properties regarding dye molecules that have been reported in this
      article are: rotational and translational diffusion coefficient and relaxation
      times. From this analysis, we estimated a range of values of 0.6-0.9 cP for the
      micro-viscosity in the mid-membrane. These simulations also afforded us some
      information regarding structural changes in the membrane as a consequence of the
      presence of the fluorescent dyes at different concentrations. Thus, the disorder
      inside the membrane, the surface area per lipid and thickness of the membrane
      were also investigated.

PMID- 17029915
TI  - Effects of cholesterol on membrane surfaces as studied by high-pressure
      fluorescence spectroscopy.
AB  - We have studied the effects of cholesterol on membrane surfaces using
      fluorescence spectroscopy at high pressure. At atmospheric pressure, the
      dissociation state of a pH-sensitive fluorophore (6-decanylnaphthol or DECNA)
      incorporated into several types of membranes showed an apparent increase in
      dissociation with cholesterol content coming somewhat closer to its dissociation
      state in solution. Previous studies have shown that when DECNA is free in
      solution, pressure induces proton dissociation due to the volume decrease that
      occurs when water electrostricts around the ions. But in phosphatidylcholine (PC)
      bilayers, proton dissociation is inhibited, either due to the inability of the
      surface to expand and allow for increased hydration, or other changes in lipid
      structure. The pressure behavior of DECNA in dioleoyl-PC, dioleoylphosphatidic
      acid and dioleylphosphatidylglycerol bilayers shows that incorporation of 5-10%
      cholesterol causes DECNA to behave like it is in a more unrestricted environment.
      This trend is reversed at higher cholesterol concentrations. These data, together
      with compressibility measurements, support the model of Sankaram and Thompson [M.
      Sankaram, T.E. Thompson, Biochemistry 29 (1990) 10676.] whereby in the disordered
      phase, cholesterol can span the two leaflets causing an increase in the area
      between the head groups; whereas in the ordered phase, no expansion occurs. Thus,
      the effect of cholesterol on membrane surfaces depends on its phase diagram.

PMID- 17029916
TI  - Heat capacity and thermodynamic characteristics of denaturation and glass
      transition of hydrated and anhydrous proteins.
AB  - Calorimetric measurements of absolute heat capacity have been performed for
      hydrated (11)S-globulin (0 < C(H(2)O) < 25%) and for lysozyme in a concentrated
      solution, both in the native and denatured states. The denaturation process is
      observed in hydrated and completely anhydrous proteins; it is accompanied by the
      appearance of heat capacity increment (Delta(N)(D)C(p)), as is the case for
      protein solutions. It has been shown that, depending on the temperature and water
      content, the hydrated denatured proteins can be in a highly elastic or glassy
      states. Glass transition is also observed in hydrated native proteins. It is
      found that the denaturation increment Delta(N)(D)C(p) in native protein, like the
      increment DeltaC(p) in denatured protein in glass transition at low water
      contents, is due to additional degrees of freedom of thermal motion in the
      protein globule. In contrast to the conventional notion, comparison of absolute
      C(p) values for hydrated denatured proteins with the C(p) values for denatured
      proteins in solution has indicated a dominant contribution of the globule thermal
      motion to the denaturation increment of protein heat capacity in solutions. The
      concentration dependence of denaturing heat absorption (temperature at its
      maximum, T(D), and thermal effect, DeltaQ(D)) and that of glass transition
      temperature, T(g), for (11)S-globulin have been studied in a wide range of water
      contents. General polymeric and specific protein features of these dependencies
      are discussed.

PMID- 17029917
TI  - Wrongful convictions, lessons learned: the Canadian experience.
AB  - Following the wrongful conviction of a man for the sexual assault and murder of a
      child, the Province of Ontario commissioned a public inquiry to prevent future
      miscarriages of justice. The implementation of several recommendations regarding
      forensic laboratory procedure and the presentation of expert evidence has proven
      to be beneficial to the Canadian criminal justice system.

PMID- 17029918
TI  - Drugged driving in Hungary 2000-2004.
AB  - The authors analyzed the biological samples available in criminal cases that were
      started because of illicit and prescribed drug-impaired driving between 2000 and
      2004. The result of the on-the-spot clinical test is not informative and cannot
      be evaluated as it is mainly affected by the simultaneous presence of alcohol.
      Licit or illicit drugs in the urine could be detected in 378 people out of 623
      people (60.7%), whereas in 59 cases (9.5%) there was some substance present in
      the blood. The occurrence multiple drugs was high (36.8%). The joint use of
      alcohol and drugs has increased in the past few years.

PMID- 17029919
TI  - The pathology of the heart conduction system in congenital heart block.
AB  - The incidence of congenital complete heart block is estimated in 1 of 2500-20,000
      births. Many cases are isolated (found in an otherwise normal heart) and the
      pathology of the heart conduction system is variable. We report a 51-year-old man
      with the diagnosis of complete heart block, with a permanent pacemaker. No family
      history of rhythm disturbances was available. The patient presented and
      endocarditis after replacement of the pacemaker battery. The prognosis was poor
      and the patient died three months later. Autopsy examination showed signs of
      shock, of septic origin. The heart was hypertrophic (450g) and the left ventricle
      thickened. Histopathological examination of the heart conduction system showed
      that the sinus and atrioventricular nodes were normal, but the His bundle was
      interrupted and replaced by fibrous tissue. No inflammatory signs were present.
      Loss of conducting fibres and their replacement by fibrous tissue is the most
      common pathological process in complete heart block. In this case His bundle was
      mostly affected, different to Lev's disease where the process is more distal
      (branching atrioventricular bundle) and to Lenegre's disease, which shows a
      diffuse damage in the conducting system.

PMID- 17029920
TI  - Spontaneous oesophageal perforation.
AB  - An autopsy was performed on a young adult, who apparently died during his sleep.
      Mediastinitis was established and empyema was also found in left pleural cavity.
      The oesophagus examination showed a tear in left side. The lesion occurred in the
      distal oesophagus and showed the leak communicating freely with the left pleural
      space. Oesophageal perforation was the source of empyema, resulted from
      barotrauma to the lower oesophagus during the effort of vomiting. Death caused by
      septic shock. Boerhaave syndrome is a serious and rapidly fatal spontaneous
      oesophagus rupture. Forceful ejection of gastric contents in an unrelaxed
      oesophagus against a closed glottis is the mechanism described. The tear thus
      produced is vertical. The case report discusses the historical, statistical,
      pathophysiological, diagnostic and therapeutic aspects of Boerhaave syndrome. The
      syndrome is a cause of sudden death, which be known by forensic pathologists.

PMID- 17029921
TI  - Forensic and criminologic aspects of murder in North-West (Epirus) Greece.
AB  - Little information is presenting in Greek literature regarding forensic and
      criminological aspects of homicide in North-West Greece. Autopsy reports and the
      prosecution authorities' files were respectively analyzed with regard to
      individual characteristics of perpetrators and victims, circumstances, and mode
      of commitment in order to comprehensively characterize relevant forensic and
      criminologic aspects. In the 8-year period from January 1998 to May 2005, 26
      homicide cases were autopsied in the Department of Forensic Medicine and
      Toxicology, University of Ioannina, Greece. Twenty-nine homicide victims (18
      males, 11 females; mean age 47 years) and 26 offenders were involved--20 single,
      4 multiple-offenders and 2 were not known (24 males, 2 females; mean age 35
      years). The most common method used for homicide was gunshot trauma (41.4%). Head
      injuries and multiple trauma were the most common cause of fatal injuries. Most
      homicides took place outside in a deserted area or close to agricultural side
      (n=12). Fifty percent (n=13) of all cases the offender and the victim were known
      to each other (acquaintances). Twenty-three cases were categorized as "single"
      homicides and 3 as "multiple" and the victims were classified; 20 as murder
      physical injury with fatal outcome, 2 homicide-suicide, 1 infanticide, 4
      matricide, and 2 as patricide.

PMID- 17029922
TI  - Molecular biology of distal muscular dystrophies--sarcomeric proteins on top.
AB  - During the last 10 years several muscular dystrophies within the group of distal
      myopathies have been clarified as to the molecular genetic cause of the disease.
      Currently, the next steps are carried out to identify the molecular pathogenesis
      downstream of the gene defects. Some early ideas on what is going on in the
      muscle cells based on the defect proteins are emerging. However, in no single
      distal muscular dystrophy these efforts have yet reached the point where direct
      trials for therapy would have been launched, and in many distal dystrophies the
      causative gene is still lacking. When comparing the gene defects in the distal
      dystrophies with the more common proximal muscular dystrophies such as
      dystrophinopathies or limb-girdle muscular dystrophies, there is a striking
      difference: the genes for distal dystrophies encode sarcomere proteins whereas
      the genes for proximal dystrophies more often encode sarcolemmal proteins.

PMID- 17029923
TI  - Comparative views of the public, sex workers, businesses and residents on
      establishing managed zones for prostitution: analysis of a consultation in
      Liverpool.
AB  - Drug addiction, violence and anti-social behaviour are characteristics of street
      prostitution. An alternative approach to zero tolerance is establishing a managed
      zone where sex workers operate according to regulations and can access health
      services. Using a consultation with sex workers (n=50), businesses (n=51),
      residents (n=179) and the public (n=789) we examined where a zone might be
      established in a UK city (Liverpool) and characteristics of the zone required by
      these stakeholders. All groups believed a zone would improve sex workers' safety
      and reduce prostitution elsewhere. Sex workers (96%) agreed to work in a zone.
      Location criteria from all groups were used to identify two potential business
      areas to host a zone but businesses in or near these areas rejected plans through
      fear for staff safety and reduced business. We discuss the consultation process,
      difficulties in locating services for marginalised groups in cities and the
      implications for health and judicial policy relating to prostitution.

PMID- 17029924
TI  - Transitions and new dynamical states induced by noise in a multiply regulated
      biochemical system.
AB  - Noise-induced transitions between coexisting states, and the emergence of a new
      oscillatory state, are examined in a model for a multiply regulated biochemical
      system. For the undisturbed system, three oscillatory states, I, II, and III,
      coexist. It is found that noise above a critical amplitude can cause a transition
      between states III and II and between states III or II and state I, whereas a
      transition from state I to either states II or III is never observed. This
      indicates that the relative stability under noise perturbations is greatest for
      state I, and progressively less for states II and III. In addition to this
      transition behaviour, a purely noise-induced state is found. Under noise
      perturbations, the average concentration of metabolites may depend on both the
      time duration and amplitude of the superimposed noise. The implications of these
      results for understanding the in vivo behaviour of complex biochemical systems
      are discussed.

PMID- 17029925
TI  - Analysis of differential scanning calorimetry data for proteins. Criteria of
      validity of one-step mechanism of irreversible protein denaturation.
AB  - We consider in this work the analysis of the excess heat capacity C(p)(ex) versus
      temperature profiles in terms of a model of thermal protein denaturation
      involving one irreversible step. It is shown that the dependences of ln C(p)(ex)
      on 1 T (T is the absolute temperature) obtained at various temperature scanning
      rates have the same form. Several new methods for estimation of parameters of the
      Arrhenius equation are explored. These new methods are based on the fitting of
      theoretical equations to the experimental heat capacity data, as well as on the
      analysis of the dependence d(ln C (p)(ex)) d ( 1 T ) on 1 T . We have applied the
      proposed methods to calorimetric data corresponding to the irreversible thermal
      denaturation of Torpedo californica acetylcholinesterase, cellulase from
      Streptomyces halstedii JM8, and lentil lectin. Criteria of validity for the one
      step irreversible denaturation model are discussed.

PMID- 17029926
TI  - Thermodynamic analysis of amines-lasalocid complex formation.
AB  - The ionophore lasalocid A selectively transports amines across lipid membranes.
      Free energy differences of amine-lasalocid complex formation reactions and the
      activation barriers of the complex transport were calculated by the finite
      difference thermodynamic integration method. Four catecholamines were treated:
      serotonin > dopamine > noradrenaline > adrenaline. The concept of transfer
      selectivity was introduced, combining binding and activation barrier
      selectivities. The transfer selectivities correlate well with the relative
      selectivities of the amines under study.

PMID- 17029927
TI  - Long-term molecular dynamics simulation of copper plastocyanin in water.
AB  - A long molecular dynamics simulation (1.1 ns) of fully hydrated plastocyanin has
      been performed and analysed to relate protein dynamics to structural elements and
      functional properties. The solvated structure is described in detail by the
      analysis of H-bond network. During all the simulation, the crystal H-bond network
      is maintained in the beta-sheet regions, while several H-bonds are broken or
      formed on the external surface of the protein. To evaluate whether such changes
      could be due to conformational rearrangements or to solvent competition, we have
      examined the average number of H-bonds between protein atoms and water molecules,
      and the root mean square deviations from crystal structure as a function of
      protein residues. Protein mobility and flexibility have been examined by
      positional and dihedral angle rms fluctuations. Finally, cross-correlation maps
      have revealed the existence of correlated motions among residues connected by
      hydrogen bonds.

PMID- 17029928
TI  - Complex dynamics of mass-closed coupled autocatalytic systems in response to
      minute asymmetric perturbations.
AB  - The role of kinetic coupling in catering to a remote-control mechanism for the
      onset and regulation of self-organization phenomena in a multicompartmental
      biochemical system has been examined. Using two cyclic autocatalytic reaction
      networks operating in two chambers separated by a membrane and coupled through a
      common cofactor, it has been demonstrated that (i) in response to asymmetric
      perturbations, the coupled reaction networks exhibit a variety of temporal self
      organization phenomena such as bistability, multiple periodicity, hard excitation
      and coexistence of aperiodic oscillation with limit cycle even in mass-closed
      conditions; (ii) without disturbing a network directly, its dynamic behaviour can
      be regulated by perturbing some other network kinetically coupled to it and (iii)
      the dynamics of two coupled networks can be made to flip-flop between oscillatory
      and steady-states simply by modulating the time of application of external
      perturbations. The extreme sensitivity of this model to minute asymmetric
      fluctuations in the environment can predict how the impact of local changes in
      physico-chemical conditions can be transmitted from one compartment to another
      through coupled biochemical pathways in a living cell.

PMID- 17029929
TI  - A correction to the calculation of the Gibbs free energy of adsorption for
      biomolecules in ion-exchange systems.
AB  - We wish to propose a correction to the methodology introduced by Gerstner et al.
      [J.A. Gerstner, J.A. Bell, S.M. Cramer, Biophys. Chem. 52 (1994) 97-106] for the
      calculation of Gibbs free energies of adsorption of biomolecules to ion-exchange
      systems. Our approach is based on the requirement that the mobile phase and
      stationary phase concentrations be expressed in exactly the same units and the
      equilibrium constant be strictly dimensionless. The Gibbs free energies of ion
      exchange calculated based on this correction appear to be more negative than
      those originally calculated by Gertner et al.

PMID- 17029930
TI  - Secondary structure of an isolated P-region from the voltage-gated sodium
      channel: a molecular modelling/dynamics study.
AB  - Conformational studies of synthetic peptides corresponding to the pore-forming
      regions of voltage-gated sodium channels show a high tendency for beta-sheet
      conformation when interacting with lipid vesicles, as revealed by circular
      dichroism and infrared spectroscopy. These observations have guided our choice of
      possible molecular models for the P-region peptide of domain II of voltage-gated
      sodium channels: three alternative beta-hairpins, with differing turn
      assignments, or an alpha-helical hairpin. After generation of models by distance
      geometry-based methods, molecular dynamics (MD) simulations were run. in the
      absence of explicit solvent molecules but employing three different dielectric
      constants, to explore possible conformational preferences. The simulations in the
      different dielectric environments suggest that a 4-residue turn with the sequence
      LCGE yields more stable beta-hairpins. The MD results suggest that the SS1 part
      of the peptide may be more stable as an alpha-helix, whereas the SS2 part tends
      to adopt a beta-conformation.

PMID- 17029931
TI  - Photosynthesis as a power supply for (bio-)hydrogen production.
AB  - Although hydrogen is considered to be one of the most promising future energy
      sources and the technical aspects involved in using it have advanced
      considerably, the future supply of hydrogen from renewable sources is still
      unsolved. This review focuses on the production of hydrogen from water using
      biological catalysts that have been optimized by nature: the process of water
      splitting photosynthesis on the one hand and hydrogen production via the catalyst
      hydrogenase on the other. Using water as a source of electrons and sunlight as a
      source of energy, both engineered natural systems and biomimetic (bio-inspired)
      model systems can be designed as first steps towards water-splitting-based
      hydrogen production (biophotolytic hydrogen production).

PMID- 17029932
TI  - The ABC's of comparative genomics in the Brassicaceae: building blocks of
      crucifer genomes.
AB  - In this review we summarize recent advances in our understanding of
      phylogenetics, polyploidization and comparative genomics in the family
      Brassicaceae. These findings pave the way for a unified comparative genomic
      framework. We integrate several of these findings into a simple system of 24
      conserved chromosomal blocks (labeled A-X). The naming, order, orientation and
      color-coding of these blocks are based on their positions in a proposed ancestral
      karyotype (n=8), rather than by their position in the reduced genome of
      Arabidopsis thaliana (n=5). We show how these crucifer building blocks can be
      rearranged to model the genome structures of A. thaliana, Arabidopsis lyrata,
      Capsella rubella and Brassica rapa. A framework for comparison between species is
      timely because several crucifer genome-sequencing projects are underway.

PMID- 17029933
TI  - [Fulminant myocarditis presenting like acute myocardial infarction in a 6-year
      old girl].
AB  - Acute myocarditis is a rare inflammatory cardiac disease in children with
      potentially fatal issue. Clinical findings are very variable from nausea and
      vomiting to acute cardiovascular collapse. The cardiac function can be reversible
      with circulatory support. We report the case of a 6-year-old girl with ECG
      changes like myocardial infarction and diagnosis of fulminant myocarditis. She
      developped rapidly a cardiogenic shock and died before treatment with mechanical
      circulatory support.

PMID- 17029934
TI  - [Listeria monocytogenes meningitis in an immunocompetent child].

PMID- 17029935
TI  - [Babywalker use (baby-trot, youpala): an unsafe practice].
AB  - AIM: Epidemiological analysis of accidents related to babywalker use admitted to
      a pediatric emergency department. METHODS: Retrospective, descriptive study of
      injuries related to babywalkers admitted to the pediatric emergency department
      between January 1st, 2003 and December 31st, 2005. RESULTS: One hundred and
      seventy-eight children were admitted due to an accident related to babywalker
      use. The sex ratio was 1.7 with a male prevalence. Mean age was 11+/-4 months.
      Seventy-eight percent of babywalker-related injuries were attributable to fall
      down a flight of stairs. The mean number of steps that a child fell down was 7
      (range 1-20 steps). The repartition of accidents was bimodal: during the year, 1
      peak in May and 1 in October; during the week: 54% of the cases occurred on
      Thursday or on the weekend; during the day (1 peak between 10 a.m. and 1 p.m. and
      1 peak between 4 p.m. and 7 p.m.). Non-severe head traumas represented the most
      frequent injury (72%). Twenty-one children were hospitalised for concussion
      (N=15), cranial fractures (N=3), forearm fracture (N=1), dental subluxation (N=1)
      and extradural hematoma (N=1). A social problem (families with unsafe domestic
      practices) was identified in 26 children (15%), 16 of these situations were
      recognized due to the retrospective character of the study and the analysis of
      hospital admissions after the first accident. CONCLUSION: Stairway related falls
      associated with babywalker use and fall down in the stairs are very frequent in
      children less than 1 year-old. This resulted in babywalkers being prohibited in
      Canada since 2004. In several countries, advocates are working to ban
      babywalkers. Active or passive prevention methods have shown their limits. This
      unsafe and dangerous practice should be banned in France.

PMID- 17029936
TI  - Detrimental effect of eicosapentaenoic acid supplementation on bone following
      ovariectomy in rats.
AB  - Although several studies have reported a positive effect of n-3 essential fatty
      acids (EFAs) on bone density post-ovariectomy, the role of specific EFAs has yet
      to be fully elucidated. In this study, ovariectomised (OVX) rats were
      supplemented with 0.1 g (LOW) or 1.0 g (HIGH) of eicosapentaenoic acid (EPA)/kg
      body weight for 9 weeks. Bone mineral density (BMD), 25-hydroxyvitamin D(3) and
      plasma fatty acid profile were compared to those of OVX and sham animals fed a
      non-supplemented diet. BMD decreased significantly in all OVX (P<0.001) but not
      sham rats. There was no difference in BMD between the LOW group and OVX controls.
      BMD was significantly lower in the HIGH group compared to OVX and sham controls.
      25-hydroxyvitamin D(3) levels were significantly higher in both the LOW and HIGH
      groups compared to OVX controls (P=0.0006 and 0.02, respectively). In conclusion,
      high-dose EPA supplementation exacerbated the effects of ovariectomy on BMD.

PMID- 17029937
TI  - Allergy and hypersensitivity: mechanisms of allergic disease.

PMID- 17029939
TI  - Social determinants of access to reference care centres for patients with
      colorectal cancer--a multilevel analysis.
AB  - BACKGROUND: Although social disparities in survival for patients with cancer are
      documented in an increasing number of papers, knowledge on the underlying
      mechanisms concerning screening, diagnosis, treatment or follow-up, is relatively
      poor. Our study was aimed at investigating the social determinants of access to
      reference cancer care centres for surgery for colorectal cancer in France.
      METHODS: Retrospective analysis was conducted on population-based data from a
      specialised cancer registry (County of Calvados, France). The population
      consisted of 5156 patients with surgical treatment for colorectal cancer recorded
      between January 1st 1981 and December 31st 2000. RESULTS: The probability of
      being cared for in a reference care centre was 1.3-fold lower for people living
      in a deprived district (mean income < 15000 euros) and 3-fold lower for people
      living in a district where more than 7% of houses were devoid of bath and shower
      in comparison with districts where this rate was under 2%. After adjustment for
      distance from reference care centre, the probability of being cared for in a
      reference care centre was still over one third lower for people living in a
      district with more than 7% of houses devoid of bath and shower. Social
      disparities in management of patients with colorectal cancer have increased in
      the last decade. The reduction of access to reference care with distance was
      stronger in elderly patients. CONCLUSIONS: There is a social and geographical
      determination of type of treatment centre for care management of colorectal
      cancer in France. Special attention needs to be paid to the high quality of care
      management in non-specialised care centres in order to avoid an increased social
      gradient in cancer mortality in France.

PMID- 17029940
TI  - Vibrational spectra of metals treated with allyltrimethoxysilane sol-gel and self
      assembled monolayer of allytrichlorosilane.
AB  - A sol-gel has been prepared by using allyltrimethoxysilane (ATMS) as precursor,
      ethanol as homogenizer as well as solvent, and hydrochloric acid as catalyst. The
      sol-gel was employed for the coating treatment of aluminum. Self-assembled
      monolayer (SAM) with allyltrichlorosilane (ATCS) is another method used for the
      metal surface treatment in the present work. The treated metal surfaces were
      characterized with reflection adsorption infrared spectra (RAIR). Detailed
      interpretation and vibrational assignment have been given to the collected IR
      spectra of the sol-gel, xerogel and surface films of ATMS and the SAM of ATCS on
      aluminum as well as pure silanes. A series of investigation of the UV exposure
      and temperature effects has been carried out. Results from the investigation
      indicate that the UV radiation exposure or the high temperature thermal treatment
      will induce a chemical process on the organosilica coated surfaces.

PMID- 17029941
TI  - Fluorescent quenching method for determination of trace hydrogen peroxide in rain
      water.
AB  - A simple and sensitive fluorescent quenching method for the determination of
      trace hydrogen peroxide (H(2)O(2)) has been proposed to determine hydrogen
      peroxide in rain water sample. The method is based on the reaction of H(2)O(2)
      with 3,3'-diethyloxadicarbocyanine iodide (DI) to form a compound which has no
      fluorescence in acetate buffer solution (pH 3.09). The maximum emission
      wavelength of the system is located at 604 nm with excitation at 570 nm. Under
      the optimal conditions, the calibration graph was obtained between the quenched
      fluorescence intensity and hydrogen peroxide concentration in the range of 5.0 x
      10(-7) to 9.0 x 10(-4) mol L(-1). The proposed method was applied to determine
      H(2)O(2) in rain water samples, and the result was satisfactory. The mechanism
      involved in the reaction was also studied.

PMID- 17029942
TI  - Vibrational spectroscopic studies of an organic non-linear optical crystal 8
      hydroxyquinolinium picrate.
AB  - 8-hydroxyquinolinium picrate (8-HQP) was synthesized by the addition of equimolar
      quantities of 8-hydroxyquinoline (8-HQ) and picric acid (PA). Single crystals
      were grown from N,N dimethyl formamide (DMF) by restricted evaporation method at
      room temperature. The solubility of 8-HQP was determined in different solvents at
      various temperatures. The structural characterization of the grown crystals was
      carried out by X-ray diffraction. Vibrational modes were classified on the basis
      of group theoretical analysis and the spectral bands were compared with those of
      parent compounds in order to propose a tentative assignment by recording FT-IR,
      FT-Raman and polarized Raman spectra in different crystal orientations. The
      crystal possess lower cut-off at 230 nm and good transparency as confirmed by
      optical transmittance studies.

PMID- 17029943
TI  - Interatomic potential parameters of CdHe van der Waals complex derived from
      excitation spectrum of the C1 1(51P1)<--X10+(51S0) vibrational transition.
AB  - The first time observed excitation spectrum of the C(1)1(5(1)P(1))<-
      X(1)0+(5(1)S(0)) transition in CdHe van der Waals molecules is reported.
      Vibrational spectrum in the UV region (2286.0-2296 A) was excited in a continuous
      molecular-jet-expansion beam of CdHe seeded in helium using an in-house-built
      nitrogen-dye laser system. The excitation spectrum exhibits two vibrational
      components (v'<--v''=0) highly broadened by means of unresolved rotational
      structure and some additional contributions of "hot-bands" components (v'<-
      v''=1). The last effect is due to an extremely small separation of the
      vibrational levels in the ground X(1)0+ state of the CdHe molecule, where v'=0
      vibrational level is separated from v''=0 by merely 6.0 cm(-1). It follows
      therefore that even in an extremely cold environment (T(v) approximately 10K) of
      a jet-expansion beam the population of v''=1 level is feasible, due to some
      residual collisions, and hence the v'<--v'=1 transitions are highly probable. The
      assignment of vibrational bands and numerical analysis of the spectrum was based
      and obtained with the aid of a rigorous computer simulation of the C(1)1<--X(1)0+
      transition including the impact of rotational structure and hot-bands
      contributions. As a result we obtained optical potential parameters of the
      C(1)1(5(1)P(1)) state of CdHe molecule which are further discussed in terms of
      our recent (and only existing) experimental results regarding the X(1)0+,
      B1(5(3)P(1)) and A0+(5(3)P(1)) states of CdHe as well as in terms of ab initio
      calculations results.

PMID- 17029944
TI  - Spectroscopic studies of charge transfer complexes between colchicine and some pi
      acceptors.
AB  - Charge transfer complexes between colchicine as donor and pi acceptors such as
      tetracyanoethylene (TCNE), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), p
      chloranil (p-CHL) have been studied spectrophotometrically in dichloromethane at
      21 degrees C. The stoichiometry of the complexes was found to be 1:1 ratio by the
      Job method between donor and acceptors with the maximum absorption band at a
      wavelength of 535, 585 and 515 nm. The equilibrium constant and thermodynamic
      parameters of the complexes were determined by Benesi-Hildebrand and van't Hoff
      equations. Colchicine in pure form and in dosage form was applied in this study.
      The formation constants for the complexes were shown to be dependent on the
      structure of the electron acceptors used.

PMID- 17029945
TI  - Heteroleptic tris-chelates of ruthenium(II): synthesis, spectral characterisation
      and electrochemical properties.
AB  - A facile reaction of cis-trans-cis-RuCl(2)(RaaiR')(2) [RaaiR'=1-alkyl-2
      (arylazo)imidazole, m-R-C(6)H(4)-NN-C(3)H(2)-NN-1-R', where R=H (a), OMe (b),
      NO(2) (c) and R'=Me (1), Et (2) and CH(2)Ph (3)] either with 2,2'-bipyridine
      (bpy) and AgNO(3) followed by NaClO(4) or [Ag(bpy)(2)](ClO(4)) in boiling acetone
      has isolated red-brown [Ru(bpy)(RaaiR')(2)](ClO(4))(2) (1a-c, 2a-c, 3a-c). The
      maximum molecular peak of [Ru(bpy)(OMeaaiMe)(2)](ClO(4))(2) (1b) is observed at
      m/z 888.01 (100%) in the FAB mass spectrum. IR spectra of the complexes show CN
      and NN stretching at 1590 and 1370cm(-1) which is red shifted by 40 and 90cm(-1)
      from the free ligand value supports Ru-azo nitrogen pi bonding interaction. The
      emission spectra in frozen glass (77K) are sharper and considerably more intense
      than the room temperature spectra. The (1)H NMR spectral measurements suggest
      methylene, -CH(2)-, in RaaiEt gives a complex AB type multiplet while in
      RaaiCH(2)Ph it shows AB type quartets. Considering two arylazoimidazole moieties
      there are 20 different carbon atoms in the molecule which gives a total of 20
      different peaks in the (13)C NMR spectrum. In the (1)H-(1)H COSY spectrum of the
      present complexes, absence of any off-diagonal peaks extending from delta=14.12
      and 9.55ppm confirm their assignment of no proton on N(1) and N(3), respectively.
      Contour peaks in the (1)H-(13)C HMQC spectrum in the present complexes, the
      absence of any contours at delta=147.12, 160.76, 155.67 and 157.68 ppm assign
      them to the C(2), C(6), C(8) and C(e and e'') carbon atoms, respectively. Cyclic
      voltammogram shows Ru(III)/Ru(II) redox couple along with three successive ligand
      reductions. The plot of difference in potential of first oxidation and reduction
      versus energy of main MLCT band (nu(CT)) is linear. Electrochemical
      parametrisation of Ru(III)/Ru(II) redox couple determines ligand potential
      E(L)(L).

PMID- 17029946
TI  - Assessment of ternary iron-cyclodextrin-2-naphthol complexes using NMR and
      fluorescence spectroscopies.
AB  - Recent research has indicated that ternary complexes can be formed among
      carboxymethyl-beta-cyclodextrin, certain polycyclic aromatic hydrocarbons (PAHs)
      (e.g. anthracene and 2-naphthol), and Fe(2+) in aqueous solution. The formation
      of these ternary complexes has been suggested as the reason for improved reaction
      efficiency in iron catalyzed Fenton degradation (H(2)O(2)+Fe(2+)-->*OH+OH(
      )+Fe(3+)) of PAHs and other pollutants. In the present work, several other
      cyclodextrins were examined to determine their ability to form similar ternary
      complexes with 2-naphthol and Fe(2+). Fluorescence and NMR techniques were
      employed in this study. Results showed that hydroxypropyl-beta-cyclodextrin, beta
      cyclodextrin, and alpha-cyclodextrin were able to encapsulate 2-naphthol
      molecules, but their binding with Fe(2+) was weak. On the contrary, sulfated-beta
      cyclodextrin has significant binding with Fe(2+), but it showed little inclusion
      of 2-naphthol molecules. Consequently, none of these four cyclodextrins formed
      significant amounts of ternary complexes in aqueous solution. The techniques used
      in this study provide useful methods for assessing the ability of cyclodextrins
      to form ternary complexes with guest compounds and metal ions.

PMID- 17029947
TI  - Spectral properties of some metal complexes derived from uracil-thiouracil and
      citrazinic acid compounds.
AB  - The reaction of FeCl(3) with uracil (H(2)L(1)), citrazinic acid (H(2)L(6)), 5
      (phenylazo)citrazinic acid (H(2)L(7)), 5-(m-hydroxyphenylazo)citrazinic acid
      (H(2)L(8)) and 5-(m-nitrophenylazo)citrazinic acid (H(2)L(9)) leads to the
      formation of complexes with the empirical formula Fe(HL)(3).nH(2)O (n=1-3). All
      of the prepared complexes have octahedral complexation geometry where the azo
      group is not the reactive site for complexation. Thiouracil (H(2)L(2)) and the 5
      (substituted phenylazo)thiouracil (H(2)L(3)-H(2)L(5)) ligands are bidentates on
      complexation with Co(II), Ni(II) and Cu(II). The complexes have been
      characterized by elemental analyses, IR, electronic spectra, magnetic
      susceptibility, DTA, electron spin resonance (copper complexes) and Mossbauer
      spectra (iron complexes). The coordination bond lengths between the metal ion and
      the active centers for complexation were calculated.

PMID- 17029948
TI  - Hormonal effects on the secretion and glycoform profile of corticosteroid-binding
      globulin.
AB  - Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily
      synthesized in the liver and binds cortisol and progesterone with high affinity.
      In this study, a CBG secreting hepatocellular carcinoma derived cell line (HepG2)
      was used to investigate the hormonal regulation of hepatic CBG synthesis. HepG2
      cells were grown for 72 h in 30, 300 and 3000 nM concentrations of estradiol
      (E2), testosterone (T), insulin, thyroxin (T4) and dexamethasone (DMZ) and the
      secreted CBG quantified by a novel enzyme-linked immunosorbent assay (ELISA). Two
      dimensional polyacrylamide gel electrophoresis (2D-PAGE) was carried out to
      determine the effects of these hormones on the relative distribution of CBG
      glycoforms. Insulin, T4 and high concentrations of E2 decreased the secretion of
      CBG by HepG2 cells (p<0.05). Ethanol, the solvent used for E2, T and DMZ, also
      significantly attenuated CBG secretion. 2D-PAGE resolved 13-14 glycoforms of CBG
      produced by HepG2 cells. Insulin caused a reduction in the synthesis of more
      acidic, while T4 and DMZ decreased the production of more basic CBG glycoforms.
      Stimulation with E2 resulted in the synthesis of additional isoforms of increased
      acidity, which may represent a type of CBG only seen during pregnancy in vivo.
      Possible physiological implications of these findings are discussed.

PMID- 17029949
TI  - Theta burst stimulation does not reliably depress all regions of the human motor
      cortex.
AB  - OBJECTIVE: The excitability of the human motor cortex projecting to hand muscles
      can be reduced by theta burst transcranial magnetic repetitive stimulation (TBS).
      This study compared the magnitude and variability of changes evoked by TBS for a
      distal and proximal arm muscle. METHODS: Eight subjects participated in three
      studies. In each study, electromyographic responses (MEPs) to single-pulse
      transcranial magnetic stimulation assessed cortical excitability before and after
      40s of TBS. In the first two studies, TBS (intensity, 80% active motor threshold)
      was delivered to the optimal locations for biceps or first dorsal interosseous
      (FDI). In the final study, weaker intensity TBS was delivered over the biceps
      representation. RESULTS: TBS targeting biceps produced highly variable results
      among subjects. For the group, MEPs were not significantly depressed. Repeat
      studies in individual subjects highlighted the variability of responses. For FDI,
      MEPs were significantly depressed 5min after TBS and remained depressed for
      >30min (p<0.05). No significant changes in biceps MEPs occurred with weaker TBS.
      CONCLUSIONS: The magnitude and reliability of TBS depends on the region of the
      cortex targeted. SIGNIFICANCE: Results obtained for the hand should not be
      considered indicative of changes that will occur in other regions of the motor
      cortex or the brain.

PMID- 17029950
TI  - Propagation of interictal discharges in temporal lobe epilepsy: correlation of
      spatiotemporal mapping with intracranial foramen ovale electrode recordings.
AB  - OBJECTIVE: We have investigated intracerebral propagation of interictal
      epileptiform discharges (IED) in patients with mesial temporal lobe epilepsy
      (MTLE) by using spatiotemporal source maps based on statistical nonparametric
      mapping (SNPM) of low resolution electromagnetic tomography (LORETA) values.
      METHODS: We analyzed 30 patterns of IED recorded simultaneously with scalp and
      intracranial foramen ovale (FO) electrodes in 15 consecutive patients with
      intractable MTLE. The scalp EEG signals were averaged time-locked to the peak
      activity in bilateral 10-contact FO electrode recordings. SNPM was applied to
      LORETA values and spatiotemporal source maps were created by allocating the t
      values over time to their corresponding Brodmann areas. Propagation was defined
      as secondary statistically significant involvement of distinct cortical areas
      separated by >15 ms. The results were correlated with intracranial data obtained
      from FO electrode recordings and with scalp EEG recordings. All patients
      underwent subsequent amygdalo-hippocampectomy and outcome was assessed one year
      after surgery. RESULTS: We found mesial to lateral propagation in 6/30 IED
      patterns (20%, four patients), lateral to mesial propagation in 4/30 IED patterns
      (13.3%, four patients) and simultaneous (within 15 ms) activation of mesial and
      lateral temporal areas in 6/30 IED patterns (20%, five patients). Propagation
      generally occurred within 30 ms and was always limited to ipsilateral cortical
      regions. Nine/30 IED patterns (30%) showed restricted activation of mesial
      temporal structures and no significant solutions were found in 5/30 IED patterns
      (16.7%). There was no clear association between the number or characteristics of
      IED patterns and the postsurgical outcome. CONCLUSIONS: Spatiotemporal mapping of
      SNPM LORETA accurately describes mesial to lateral temporal propagation of IED,
      and vice versa, which commonly occur in patients with MTLE. SIGNIFICANCE:
      Intracerebral propagation must be considered when using non-invasive source
      algorithms in patients with MTLE. Spatiotemporal mapping might be useful for
      visualizing this propagation.

PMID- 17029951
TI  - The influence of Mozart's music on brain activity in the process of learning.
AB  - OBJECTIVE: The study investigated the influence Mozart's music has on brain
      activity in the process of learning. A second objective was to test priming
      explanation of the Mozart effect. METHODS: In Experiment 1 individuals were first
      trained in how to solve spatial rotation tasks, and then solved similar tasks.
      Fifty-six students were divided into 4 groups: a control one--CG who prior to and
      after training relaxed, and three experimental groups: MM--who prior to and after
      training listened to music; MS--who prior to training listened to music and
      subsequently relaxed; and SM--who prior to training relaxed and afterward
      listened to music. The music used was the first movement of Mozart's sonata (K.
      448). In Experiment 2, thirty-six respondents were divided into three groups: CG,
      MM (same procedure as in Experiment 1), and BM--who prior to and after training
      listened to Brahms' Hungarian dance No. 5. In both experiments the EEG data
      collected during problem solving were analyzed using the methods of event-related
      desynchronization/synchronization (ERD/ERS) and approximated entropy (ApEn).
      RESULTS: In the first experiment the respondents of the MM, MS, and SM groups
      showed a better task-performance than did the respondents of the CG group.
      Individuals of the MM group displayed less complex EEG patterns and more alpha
      band synchronization than did respondents of the other three groups. In
      Experiment 2 individuals who listened to Mozart showed a better task performance
      than did the respondents of the CG and BM groups. They displayed less complex EEG
      patterns and more lower-1 alpha and gamma band synchronization than did the
      respondents of the BM group. CONCLUSIONS: Mozart's music, by activating task
      relevant brain areas, enhances the learning of spatio-temporal rotation tasks.
      SIGNIFICANCE: The results support priming explanation of the Mozart effect.

PMID- 17029952
TI  - H-reflex depression by propofol and sevoflurane is dependent on stimulus
      intensity.
AB  - OBJECTIVE: The H-reflex has been widely used to investigate effects of drugs on
      motoneuron excitability in humans. However, up to now no systematic investigation
      has been done to examine the effects at different stimulus intensities. Here, the
      M. soleus recruitment curves were compared under influence of propofol and
      sevoflurane with control conditions to investigate these stimulus intensity
      dependent effects. METHODS: The study was performed in 10 volunteers for propofol
      and sevoflurane each, aged 23-32 years. The M. soleus H-reflex was evoked by
      stimulation of the tibial nerve. Recruitment curves were gained by increasing the
      stimulation current stepwise from below the threshold of a minimal H-reflex up to
      a maximal (m-response. Measurements were performed under the influence of the
      respective drug (2mg/l propofol, 0.8 vol% sevoflurane) and compared to control
      measurements before and after drug administration. RESULTS: The relative amount
      of depression of the H-reflex at high stimulus intensities is for both drugs
      significantly (p<0.001, Friedman's test) lower than at low stimulus intensities.
      CONCLUSIONS: Stimulus dependent effects have to be taken into consideration when
      experimental settings to investigate the effects of drugs on the H-reflex are
      being designed. According to the size principle of motoneuron excitation, it can
      also be assumed that under the influence of propofol and sevoflurane larger
      motoneurons are not depressed in the same amount as smaller motoneurons.
      SIGNIFICANCE: Different drug effects on the H-reflex at different stimulus
      intensities are not only of methodological importance, but also indicate
      different drug effects on motoneurons of different sizes.

PMID- 17029953
TI  - Effects of GPi stimulation on human thalamic neuronal activity.
AB  - OBJECTIVE: Determine the effects of globus pallidus interna (GPi) deep brain
      stimulation (DBS) on ventral oralis posterior nucleus of the thalamic (Vop)
      neuronal activity. METHODS: Microelectrode recordings in Vop during high
      frequency DBS GPi in a patient with dystonia. RESULTS: Twelve (48%) of 25 neurons
      in five locations neurons decreased their average discharge frequency, 2 (8%)
      increased and 11(44%) demonstrated no overall change. The patterns of responses
      were complex with periods of increase and decreased activity. All neurons were
      inhibited for the time period 3.5-5ms following the DBS pulse. Eighty-eight
      percent of neurons showed brief but highly consistent increases in the first 1ms
      following stimulation, 52% showed increased activities from 1.5 to 3ms. Twenty
      four percent of neurons increased activity following inhibition. CONCLUSIONS:
      These findings are consistent with DBS activation of GPi axons to Vop and
      probable antidromic activation of Vop axons. SIGNIFICANCE: The physiological
      effects of DBS are far more complicated and will escape any theory that does not
      address the mechanisms of DBS as stimulation of a complex network of
      interactions. Further, the findings of post-inhibitory rebound increased raises
      questions about the role in inhibition in the current concepts of basal ganglia
      physiology.

PMID- 17029954
TI  - Extended BSI for continuous EEG monitoring in carotid endarterectomy.
AB  - OBJECTIVE: Carotid endarterectomy is a common procedure as a secondary prevention
      of stroke, and is often performed with selective shunting. Although various EEG
      parameters have been proposed to determine if the brain is at risk during carotid
      artery clamping, the common procedure is still the visual assessment of the EEG.
      Here, we propose an extension to the previously described brain symmetry index
      (BSI) [van Putten M, Peters J, Mulder S, de Haas J, Bruijninckx C, Tavy D. A
      brain symmetry index (BSI) for online EEG monitoring in carotid endarterectomy.
      Clin Neurophysiol 2004, 115(5), 1189-94.], as an additional quantitative
      criterion for shunt need in carotid endarterectomy. METHODS: An extension of the
      Brain Symmetry Index was implemented to capture both spatial (hemispheric) (sBSI)
      and temporal changes (tBSI) in the EEG. In this pilot study, the method is
      exemplified by simulation and by application to EEG records from 25 patients who
      underwent a carotid endarterectomy. RESULTS: Simulations show that hemispheric
      asymmetry is captured by changes in sBSI, only, while temporal symmetry changes,
      not due to changes in hemispheric asymmetry, are reflected by changes in tBSI.
      Combinations of changes induced changes in both parameters. This was confirmed by
      analysis 25 EEG records. Unilateral EEG changes during test-clamping are
      reflected by DeltasBSI>0.05, diffuse changes by DeltatBSI>0.02 and combinations
      by simultaneous changes in both features. CONCLUSIONS: In this pilot study, we
      present a doublet of quantitative EEG features, that in principle detects any
      change in the spectral characteristics of the EEG, decomposing the changes into a
      measure that captures spatial symmetry changes (sBSI), and a measure that
      quantifies diffuse temporal changes, that are not due to changes in spatial
      symmetry (tBSI). Both features are normalized with values ranging from [0-1], and
      can easily be implemented on-line to support the visual analysis of the EEG in
      the decision for selective shunting. SIGNIFICANCE: Quantitative real-time EEG
      analysis will assist in the EEG interpretation for selective shunting in carotid
      endarterectomy.

PMID- 17029955
TI  - Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale
      electrodes.
AB  - OBJECTIVE: We introduce a monopole model to examine the sources of ictal and
      interictal activity in mesial temporal lobe epilepsy (MTLE) recorded using
      foramen ovale electrodes (FOE). METHODS: Classical electrostatic theory was
      applied to derive mathematical expressions. Interictal and ictal activity was
      acquired using FOE and scalp video-electroencephalography (v-EEG) during awake
      and sleep states. A total of 2057 interictal spikes and 712 ictal spikes were
      analyzed. Thirty-five seizures from several consecutive episodes were examined.
      MRI and clinical data were correlated with voltage source localization. RESULTS:
      Patients (20) were grouped according to the spatial distribution of voltage
      sources of interictal activity. Voltage sources were located over 3.4 and 21.6mm
      in the anterior-to-posterior axis of mesiotemporal structures and separated no
      more than 7 mm from this axis. In most patients (16), sources were restricted to
      11.1+/-1.5mm, whereas other patients (4) exhibited a wider distribution (29.6
      43.5mm). Sources of ictal and interictal activity partially overlapped, with
      ictal sources exhibiting a posterior localization at 20-40 mm. Both interictal
      and ictal sources were anterior to MRI atrophy. No difference between awake and
      sleep states were found, neither correlation between source scattering and
      history of epilepsy. CONCLUSIONS: Voltage source analysis applied to FOE suggests
      that, in most MTLE patients, interictal activity emerges from very restricted
      areas. Some patients, however, exhibited sources which are distributed all along
      the mesiotemporal structures. Our data suggest an anterior-to-posterior alignment
      of the irritative, ictal and atrophic zones. SIGNIFICANCE: The voltage source
      model applied to FOE can help to map the extension of the irritative and ictal
      areas in mesiotemporal structures.

PMID- 17029956
TI  - Altered diurnal autonomic variation and reduced vagal information flow in acute
      schizophrenia.
AB  - OBJECTIVE: This study aimed to further investigate autonomic function in
      schizophrenic patients using long-term electrocardiographic (ECG) recordings.
      METHODS: Twenty unmedicated patients suffering from an acute episode of paranoid
      schizophrenia and 20 matched control subjects were recruited and 24-h ambulatory
      electrocardiograms were recorded. In order to investigate complexity of heart
      rate fluctuations related to different physiological time scales, linear heart
      rate variability (HRV) as well as autonomic information flow (AIF) parameters
      were calculated from day and night time intervals. RESULTS: While heart rates
      were increased, root mean successive square difference (RMSSD), a measure for
      vagal function as well as standard deviation of 5-min mean NN-intervals (SDANN),
      reflecting parasympathetic and sympathetic tone, were decreased in schizophrenia.
      Furthermore, a decrease of vagal information flow was apparent during night time
      (decreased mean high frequency peak decay (PD(mHF))). In addition, increased
      INT(NN) (area under the AIF curve) as well as decreased beat decay (BD(NN)) and
      mean very low frequency PD (PD(mVLF)) indicated reduced complexity in patients
      during day and night time. CONCLUSIONS: HRV and AIF parameters indicate altered
      diurnal autonomic variation in schizophrenia. SIGNIFICANCE: Reduced vagal
      modulation and loss of complexity might both contribute to the increased risk for
      sudden cardiac death in schizophrenia.

PMID- 17029957
TI  - Effect of pretreatment severity on xylan solubility and enzymatic breakdown of
      the remaining cellulose from wheat straw.
AB  - The effect of process conditions used for wheat straw pretreatments on the liquor
      and residue-composition was studied. Hereto, the pretreatment conditions were
      expressed in a 'combined severity R(0)(')-factor'. The higher the combined
      severity factor (R(0)(')) the more xylan was released from the wheat straw, but
      the more xylan decomposed and furfural formation occurred. The percentage of
      residual xylan present after pretreatment appeared to be a good indicator
      concerning cellulose degradability or bio-ethanol production. Namely, cellulose
      degradation by using commercial enzymes was higher at higher severities
      corresponding to a lower amount of residual xylan. The xylan release and
      degradation was studied in more detail by using HPSEC and MALDI-TOF mass
      spectrometry. The more severe the treatment the more (acetylated) xylose
      oligomers with a DP lower than nine were analysed. The presence of (acetylated)
      xylans with a DP of 9-25 increased slightly from low to medium severity. The
      quantification of the DP-distribution of the (acetylated) xylans released proved
      to be a good tool to predict cellulose degradability.

PMID- 17029958
TI  - Toluene mineralization by denitrification in an up flow anaerobic sludge blanket
      (UASB) reactor.
AB  - In order to examine the effect of easily degradable substrate such as acetate on
      toluene mineralization by denitrification, an upflow anaerobic sludge blanket
      (UASB) reactor in steady state was set up. The experimentation was carried out in
      two stages. Initially, the reactor was fed with a carbon loading rate of 250 mg
      acetate-C L-1 d-1 as electron source. Nitrate loading rate (mg ) was adjusted to
      obtain a constant C/N ratio of 1.4. In the second stage, five toluene-C loading
      rates (TLR, mg toluene-C L-1 d-1), 25, 50, 75, 100 and 125, were assessed while
      total carbon loading rate and C/N were maintained constant at 250 mg C L-1 d-1
      and 1.4, respectively. In so doing, acetate-C loading rate (mg acetate-C L-1 d-1)
      was gradually substituted by toluene-C. When acetate-C was the only electron
      source a dissimilative denitrifying process resulted as indicated by bicarbonate
      yield YHCO3, mg produced/mg carbon consumed) of 0.74 +/- 0.005 and denitrifying
      yield (YN2, mg N2 produced/mg consumed) of 0.89 +/- 0.042. The addition of
      different TLR did not affect the biological process as consumption carbon
      efficiency (CCE) values remained up to 95% +/- 3.5 and YHCO3 and YN2 values were
      higher than 0.71 +/- 0.03 and 0.88 +/- 0.01, respectively. Toluene mineralization
      by denitrification in continuous culture was successfully achieved. A simple UASB
      denitrifying reactor system has promising applications for complete conversion of
      nitrate, toluene and acetate into N2 and CO2 with a minimal sludge production.

PMID- 17029959
TI  - Effects of combined deferiprone and desferrioxamine iron chelating therapy in
      beta-thalassemia major end-stage heart failure: a case report.
AB  - Despite usual iron chelating therapy based on desferrioxamine, patients affected
      by beta-thalassemia major (beta-TM) often develop progressive heart failure
      caused by myocardial iron overload, which is the leading cause of mortality
      within the third decade of life. Heart transplantation is a limited therapeutic
      option, as very often these patients have multi-organ iron deposits and infective
      complications (particularly hepatitis C), secondary to frequent blood
      transfusions. We report the case of a 26-year-old male affected by beta-TM with
      end-stage heart failure, who showed a dramatic improvement in symptoms and
      myocardial function when a new oral iron chelating agent, deferiprone, was added
      to standard therapy with desferrioxamine.

PMID- 17029960
TI  - Tibial translation in exercises used early in rehabilitation after anterior
      cruciate ligament reconstruction exercises to achieve weight-bearing.
AB  - Accelerated rehabilitation after ACL reconstruction involves early weight
      bearing. Exercises designed to achieve weight-bearing should be effective for the
      neuromuscular system and protect the knee from excessive anterior tibial
      translation. The aim of this study was to assess the anterior tibial translation
      under two different body-weight shift exercises at 2 weeks post-ACL
      reconstruction and compare this with healthy controls. METHODS: Seven patients at
      2 weeks after ACL reconstruction and seven controls participated in the study.
      Dynamic sagittal tibial translation was registered during two body weight shift
      exercises (from side to side and forward-backward). RESULTS: There was no
      significant difference in maximal translation between the two exercises in the
      ACL-reconstructed group. In the control group, the body weight shift from side-to
      side exercise resulted in larger anterior translation compared to the forward
      backward body weight shift. CONCLUSIONS: Two weeks after ACL reconstruction, both
      body weight shift exercises can be used to train body weight acceptance.

PMID- 17029961
TI  - Hemilaterally symptomatic bipartite patella associated with bone erosions arising
      from a gouty tophus: a case report.
AB  - Symptomatic bipartite patella in adults is rare. We have treated an unusual case
      of a bipartite patella in an adult, which became symptomatic in association with
      cystic degeneration localized to the patella and a gouty tophus. Although the
      patient had bilateral bipartite patellae, multiplanar reformation with computed
      tomography (CT-MPR) clearly demonstrated that the bipartite portion of the
      patella was malaligned at the junction of the accessory bone and patella in the
      symptomatic knee. Bone erosions were present both in the bipartite fragment and
      adjacent portion of the patella. After surgical excision of the bipartite
      fragment, the patient's symptoms have improved. This case illustrates that cyst
      formation associated with inflammatory arthritis may be a rare cause for a
      bipartite patella in an adult to become symptomatic.

PMID- 17029962
TI  - From insects to human hosts: Identification of major genomic differences between
      entomopathogenic strains of Photorhabdus and the emerging human pathogen
      Photorhabdus asymbiotica.
AB  - Pathogenic bacteria of the genus Photorhabdus are naturally found in symbiotic
      association with soil entomopathogenic nematodes, and are of increasing economic
      interest in view of their potential for the development of novel biopesticides.
      This bipartite natural system is currently used for the biological control of
      crop pests in several countries. However, an increasing number of Photorhabdus
      strains have recently been isolated from human clinical specimens in both the
      United States and Australia, associated with locally invasive soft tissue
      infections and disseminated bacteraemia. In view of their growing use in
      biological control, which increases the potential rate of exposure of humans to
      these pathogens, we decided to undertake a comparative study of the genomic
      differences between insect and human pathogenic strains of Photorhabdus, in an
      attempt to understand the genetic mechanisms involved in the apparent change of
      host specificity, presumably responsible for their recently acquired capacity to
      infect humans. The data presented here demonstrates that major genomic
      differences exist between strains of Photorhabdus exhibiting virulence against
      insects or humans. Several individual genes, coding for virulence factors, were
      isolated and shown to be specific to the Photorhabdus asymbiotica human
      pathogens. One of these genes, sopB, encoding a host cell invasion factor
      translocated via the type III secretion system, has been cloned and the
      comparison of its genomic context in different pathogens strongly indicates that
      horizontal gene transfer is implicated in the acquisition of these virulence
      factors specific to the human pathogens. The precise role of this and other
      virulence factors identified here in the pathogenicity of P. asymbiotica towards
      humans is currently under investigation.

PMID- 17029963
TI  - PlasmoDB v5: new looks, new genomes.
AB  - Version 5.1 of PlasmoDB, a resource for malaria parasite genomic and functional
      genomics datasets, was released in August 2006. This new release includes
      additional Plasmodium genomes and a newly designed website. The new site reflects
      the status of PlasmoDB as a member of a linked family of Apicomplexan databases.

PMID- 17029964
TI  - Modern approaches to a rapid diagnosis of tuberculosis: promises and challenges
      ahead.
AB  - The limitations of the conventional methods for diagnosing tuberculosis have
      spurred multi-faceted research activities in this field throughout the world.
      Chromatographic methods appear promising but may not be widely available in the
      developing countries. Immuno-diagnostic methods using combinations ("cocktails")
      of antigens have high sensitivity and specificity and can easily be applied in
      the peripheral laboratories and in the field settings. Though expensive,
      molecular methods for diagnosis of tuberculosis have advantages of speed,
      sensitivity, and specificity. Adequate training of the eligible personnels in
      molecular methods and prevention of laboratory-dependent contamination may help
      reduce false positive results. Although, there are no clear guidelines, so far on
      how to make out the best from the gene amplification methods, yet their use may
      be encouraged with adequate quality controls, because of the inherent ingenuity
      and promises of these methods. Phage-based molecular methods provide rapid
      results in susceptibility tests for anti-tubercular drugs. In future, many
      sophisticated techniques are expected to hit the market for a rapid diagnosis of
      tuberculosis. In the developing countries, it is necessary to evaluate
      availability of suitable infrastructure and trained personnels before adopting
      modern diagnostic methods.

PMID- 17029968
TI  - Comparison between fluorimetry and oximetry techniques to measure photosynthesis
      in the diatom Skeletonema costatum cultivated under simulated seasonal
      conditions.
AB  - This study reports comparison of two techniques measuring photosynthesis in the
      ubiquitous diatom Skeletonema costatum, i.e., the classical oximetry and the
      recent modulated fluorimetry. Microalgae in semi-continuous cultures were exposed
      to five different environmental conditions simulating a seasonal effect with co
      varying temperature, photoperiod and incident light. Photosynthesis was assessed
      by gross rate of oxygen evolution (P(B)) and the electron transport rate (ETR)
      measurements. The two techniques were linearly related within seasonal treatments
      along the course of the P/E curves. The light saturation intensity parameters (Ek
      and Ek(ETR)), and the maximum electron transport rate increased significantly
      with the progression of the season while the maximum light utilization efficiency
      for ETR (alpha(ETR)) was constant. By contrast, the maximum gross oxygen
      photosynthetic capacity (Pmax(B)) and the maximum light utilization efficiency
      for P(B) (alpha(B)) increased from December to May treatment but decreased from
      May to July treatment. Both techniques showed clear photoacclimation in
      microalgae with the progression of the season, as illustrated by changes in
      photosynthetic parameters. The relationship between the two techniques changed
      when high temperature, photoperiod and incident light were combined, possibly due
      to an overestimation of the PAR--averaged chlorophyll-specific absorption cross
      section. Despite this change, our results illustrate the strong suitability of in
      vivo chlorophyll fluorimetry to estimate primary production in the field.

PMID- 17029965
TI  - CRE-mediated transcription and COX-2 expression in the pilocarpine model of
      status epilepticus.
AB  - Status epilepticus (SE) triggers neuronal death, reactive gliosis and remodeling
      of synaptic circuitry, thus leading to profound pathological alterations in CNS
      physiology. These processes are, in part, regulated by the rapid upregulation of
      both cytotoxic and cytoprotective genes. One pathway that may couple SE to
      transcriptionally dependent alterations in CNS physiology is the CREB (cAMP
      response element-binding protein)/CRE (cAMP response element) cascade. Here, we
      utilized the pilocarpine model of SE on a mouse strain transgenic for a CRE
      reporter construct (beta-galactosidase) to begin to characterize how seizure
      activity regulates the activation state of the CREB/CRE pathway in both glia and
      neurons of the hippocampus. SE triggered a rapid (4-8 h post-SE) but transient
      increase in CRE-mediated gene expression in the neuronal sublayers. In contrast
      to neurons, SE induced a lasting increase (up to 20 days) in CRE-mediated
      transcription in both reactive astrocytes and microglia. CRE-mediated gene
      expression correlated with expression of the pro-inflammatory enzyme
      cyclooxygenase-2 (COX-2). To examine the role of CREB in SE-induced COX-2
      expression, we generated a transgenic mouse strain that expresses A-CREB, a
      potent repressor of CREB-dependent transcription. In these animals, the capacity
      of SE to stimulate COX-2 expression was markedly attenuated, indicating that CREB
      is a key intermediate in SE-induced COX-2 expression. Collectively these data
      show that SE triggers two waves of CREB-mediated gene expression, a transient
      wave in neurons and a long-lasting wave in reactive glial cells, and that CREB
      couples SE to COX-2 expression.

PMID- 17029969
TI  - Ultrastructural and autoradiographical analysis show a faster skin repair in He
      Ne laser-treated wounds.
AB  - There are evidences that low-intensity red laser radiation is capable to
      accelerate wound healing. Nowadays, this therapy has been gradually introduced in
      clinical practice although mechanisms underlying laser effects are poorly
      understood. To better understand the photobiological effects of laser radiation,
      this study investigated by electron microscopy, immunohistochemistry and
      autoradiography the morphological and functional features of irradiated and none
      irradiated injured mice skin. Full-thickness skin lesions were created on the
      back of mice and irradiated on days 1, 5, 8, 12, and 15 post-wounding with a He
      Ne laser (lambda=632.8nm), dose 1J/cm(2), exposure time 3min. Non-irradiated
      lesions were used as a control. The mice were inoculated with (3)H-proline and
      sacrificed one hour after on the 8th, 15th and 22nd days to histological and
      radioautographical analysis. The irradiated-lesions showed a faster
      reepithelization compared with control lesions. The irradiated dermis contained a
      higher number of activated fibroblasts compared to control group and, most of
      them showed several cytoplasmic collagen-containing phagosomes. In irradiated
      lesions, smooth muscle alpha-actin positive cells predominated, which correspond
      to a higher number of myofibroblasts observed in the electron microscope.
      Moreover, laser radiation reduced the local inflammation and appears to influence
      the organization of collagen fibrils in the repairing areas. Quantitative
      autoradiography showed that the incorporation of (3)H-proline was significantly
      higher in irradiated-dermis on the 15th day post-wounding (p<0.05). These results
      suggest that laser radiation may accelerate cutaneous wound healing in a murine
      model.

PMID- 17029966
TI  - Autoimmunity versus tolerance: can dying cells tip the balance?
AB  - Apoptosis is a physiological process of self-destruction for cells that are
      damaged or programmed to die. Apoptosis occurs through a series of regulated
      events that allow cellular debris to be contained and efficiently phagocytosed
      without initiating a proinflammatory immune response. Recent data have linked
      physiological apoptosis and the uptake of apoptotic cells by macrophages and some
      subsets of dendritic cells to the maintenance of peripheral immune tolerance.
      However, when cells die through necrosis, spilling their intracellular contents,
      or are infected with various pathogens, activation of antigen-presenting cells
      and induction of an immune response can occur. Receptors for extrinsic pathogen
      associated structures, such as membrane bound Toll-like receptors (TLRs) or
      intracellular Nod-like receptors (NLRs) can also respond to cross-reactive host
      molecules from dying cells and may focus autoimmune responses onto these
      antigens. Several autoimmune disorders have been linked to defects in the
      apoptotic process. Defective apoptosis of immune cells leads to autoimmunity, as
      in autoimmune lymphoproliferative syndrome (ALPS) associated with mutations in
      the death receptor Fas. Defective clearance of apoptotic cell debris can also
      lead to autoantibody production. We will discuss how cell death and apoptotic
      cell clearance may affect the finely tuned balance between peripheral immune
      tolerance and autoimmunity.

PMID- 17029970
TI  - Phytochrome-like responses in Euglena: A low fluence response that reorganizes
      the spectral dependence of the high irradiance response in long-day photoperiodic
      induction of cell division.
AB  - Irradiance spectra change spatiotemporally, and angiosperms adapt accordingly,
      mainly through phytochromes. This study challenges the long-held belief that the
      flagellated alga Euglena gracilis lacks phytochromes and is therefore unaffected
      by spectral changes. We photoautotrophically cultured the alga under continuous
      light (LL), then transferred it to darkness. After about 26h in darkness,
      different irradiations for 3h enabled cell division in dark-arrested G2 cells
      evoking a high-irradiance response (HIR). The spectral characteristics of the
      irradiation during the LL period (pre-irradiation) defined the spectral
      sensitivity in the subsequent dark period. LL with light rich in the red spectrum
      led to a HIR to the red spectrum (R-HIR), whereas light rich in the far-red
      spectrum (FR) led to a FR-HIR. Finishing the period of pre-irradiation consisting
      of continuous cool-white fluorescent light (rich in R) by a FR pulse enhanced the
      characteristics of the FR-HIR 26h later. By contrast, a R pulse given at the end
      of the pre-irradiation rich in FR potentiated the R-HIR. The effects were
      completely photoreversible between R and FR with critical fluences of about
      2mmolm(-2), satisfying the classic diagnostic feature of phytochromes. The action
      spectrum of the FR effect at the end of pre-irradiation consisting of continuous
      cool-white fluorescent light (rich in R) had a main peak at 740nm and a minor
      peak at 380nm, whereas antagonization of the FR effect had a main peak at 640nm
      and a minor peak at 480nm. Wavelengths of 610 and 670nm appeared in both spectra.
      We also demonstrated the photoreversibility of 380/640, 480/740, and (610 and
      670)/(640 and 740) nm. We conclude that Euglena displays phytochrome-like
      responses similar to the 'shade avoidance' and 'end-of-day FR' effects reported
      in angiosperms.

PMID- 17029971
TI  - High irradiance responses involving photoreversible multiple photoreceptors as
      related to photoperiodic induction of cell division in Euglena.
AB  - Little is known about the photoreceptors involved in the photoperiodism of
      unicellular organisms, which we elucidated by deriving their action spectra. The
      flagellated alga Euglena gracilis exhibits photoperiodism, with a long-day
      response in cell reproduction. The underlying clock is a circadian rhythm with
      photoinductive capability, peaking at subjective dusk and occurring at the 26th
      hour in continuous darkness (DD) when transferred from continuous light (LL); it
      regulates photoinduction, a high-irradiance response (HIR), of a dark-capability
      of progressing through cell division. We derived the action spectra by
      irradiating E. gracilis with monochromatic light for 3h at around the 26th hour;
      the action maxima occurred at 380, 450-460, 480, 610, 640, 660, 680, and 740nm.
      Except for the maximum at 450-460nm, which was always a major maximum, the maxima
      greatly depended on the red (R)/far-red (FR) ratio of the prior LL. The high R/FR
      ratio resulted in a dominant major peak at 640nm and minor peaks at 480 and
      680nm, whereas the low ratio resulted in dominant major peaks at 610 and 740nm
      and minor peaks at 380 and 660nm; the critical fluence was minimally about
      60mmolm(-2). These HIRs resulted from the accumulation of corresponding low
      fluence responses (LFRs) because we found that repetition of a 3-min light/dark
      cycle, with critical fluences of 1mmolm(-2), lasting for 3h resulted in the same
      photoinduction as the continuous 3-h irradiation. Moreover, these LFRs expressed
      photoreversibility. Thus, photoperiodic photoinduction involves Euglena
      phytochrome (640 and 740nm) and blue photoreceptor (460nm). Although 380, 480,
      610, 660, and 680nm may also represent Euglena-phytochrome, a definite conclusion
      awaits further study.

PMID- 17029972
TI  - Color of illumination during growth affects LHCII chiral macroaggregates in pea
      plant leaves.
AB  - To determine whether the color of illumination under which plants are grown,
      affects the structure of photosynthetic antennae, pea plants were grown under
      either blue-enriched, red-enriched, or white light. Carotenoid content of
      isolated chloroplasts was found to be insensitive to the color of illumination
      during growth, while chlorophyll a/b ratio in chloroplasts isolated from young
      illuminated leaves showed susceptibility to color. Color of illumination affects
      the LHCII chiral macroaggregates in intact leaves and isolated chloroplasts,
      providing light-induced alteration of the handedness of the LHCII chiral
      macroaggregate, as measured with circular dichroism and circularly polarized
      luminescence. The susceptibility of handedness to current illumination (red light
      excitation of chlorophyll fluorescence) is dependent on the color under which the
      plants were grown, and was maximal for the red-enriched illumination. We propose
      the existence of a long-term (growth period) color memory, which influences the
      susceptibility of the handedness of LHCII chiral macroaggregates to current
      light.

PMID- 17029973
TI  - The Judith Hoyer Lecture: genes, pixels, patterns, and prevention.

PMID- 17029974
TI  - Driving prevalence and factors associated with driving among patients with
      epilepsy.
AB  - PURPOSE: The goal of the work described here was to determine the prevalence of
      driving and associated variables among patients followed at a level 4 epilepsy
      center. METHOD: A survey was mailed out to patients seen at the University of
      Florida/Jacksonville Comprehensive Epilepsy Program. RESULTS: The study
      population comprised 308 respondents. Nearly 20% of patients with poorly
      controlled seizures continued to drive. Although several demographic and clinical
      variables were associated with driving, on univariate analysis, using multiple
      logistic regression, being employed, not receiving disability benefits, having
      less frequent seizures, and taking fewer antiepileptic drugs were the variables
      independently associated with driving. A subset analysis of patients with poorly
      controlled seizures indicated that being employed was still an independent factor
      associated with driving, along with higher annual household income and absence of
      convulsions and waking seizures. CONCLUSION: A significant number of patients
      with poorly controlled seizures drive. Being employed is a major reason these
      patients continue to drive.

PMID- 17029975
TI  - A multicenter, randomized, double-blind, placebo-controlled trial of long-term
      ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL): the
      study protocol [EudraCT no.: 2006-000032-27].
AB  - There is no treatment for Charcot-Marie-Tooth disease 1A (CMT1A), but ascorbic
      acid (AA) is efficacious in the transgenic mouse model. Thus, a clinical trial of
      AA in CMT1A is warranted. The CMT-TRIAAL is a phase III randomized, double-blind,
      placebo-controlled study involving 222 CMT1A adults from eight Italian centers.
      Eligible for the study are symptomatic adults with genetically confirmed CMT1A.
      Treatment consists of 2-year oral AA (1500mg/day) or placebo. The primary trial
      endpoint is an improvement in CMT Neuropathy Score. Secondary efficacy endpoints
      are changes in distal arm and leg maximum voluntary isometric contraction; 10m
      timed walking; 9-hole-peg test; overall neuropathy limitations scale; pain and
      fatigue visual analog scales; health-related quality of life (SF-36); and
      electrophysiology. Clinical-electrophysiological assessments are performed at
      baseline and every 6 months thereafter. In consenting patients from three
      centers, skin biopsy is performed to evaluate PMP22 expression. The study will
      last 34 months, starting from March 2006.

PMID- 17029976
TI  - Mitochondrial processing of bovine adrenal steroidogenic acute regulatory
      protein.
AB  - Steroidogenic acute regulatory (StAR) protein is an important regulatory protein
      in steroidogenesis and rapidly undergoes proteolysis after import into the
      mitochondria. In this study, we determined the proteolytic cleavage sites and
      investigated the effects on the stimulation of steroidogenic activity of the
      blockage of these sites by mutation. The cleaved StAR proteins, which were
      purified using an anti-StAR immobilized column, reacted with antiserum against
      the StAR C-terminal oligopeptide. The molecular weights of the purified proteins
      were determined by MALDI-TOF mass spectrometry, and were found to be identical to
      those of the 40-285 and 55-285 amino-acid-regions of the StAR protein. To confirm
      the identification of the cleavage sites, we constructed site-directed mutants of
      bovine StAR cDNA, which contained the amino acids R37A/R38A/L40A and/or
      R53A/R54A/R55A. These mutant StAR proteins expressed in COS-1 cells were not
      cleaved at positions 39-40 and 54-55, and were processed at sites different from
      those in the wild-type StAR protein. These mutant proteins stimulated
      pregnenolone formation at almost the same rate as the wild-type StAR protein in
      COS-1 cells, which suggests that the cholesterol transfer activity was not
      affected by the mutation.

PMID- 17029977
TI  - A constant-momentum/energy-selector time-of-flight mass spectrometer.
AB  - A matrix assisted laser desorption/ionization time-of-flight mass spectrometer
      has been built with an ion source that can be operated in either constant-energy
      or constant-momentum acceleration modes. A decreasing electric field distribution
      in the ion-accelerating region makes it possible to direct ions onto a space
      focal plane in either modes of operation. Ions produced in the constant-momentum
      mode have velocities and, thus, flight times that are linearly dependent on mass
      and kinetic energies that are inversely dependent on mass. The linear mass
      dispersion doubles mass resolving power of ions accelerated with space-focusing
      conditions in constant-momentum mode. The mass-dependent kinetic energy is
      exploited to disperse ions according to mass in a simple kinetic energy filter
      constructed from two closely spaced, oblique ion reflectors. Focusing velocity of
      ions of the same mass can substantially improve ion selection for subsequent post
      source decay or tandem time-of-flight analyses.

PMID- 17029978
TI  - Analysis of phenolic compounds in rhubarbs using liquid chromatography coupled
      with electrospray ionization mass spectrometry.
AB  - Rhubarb is an important herbal medicine for the treatment of constipation,
      inflammation, and cancer. In this study, a facile method based on liquid
      chromatography coupled with electrospray ionization tandem mass spectrometry has
      been established for the analysis of bioactive phenolic compounds in rhubarbs.
      From six rhubarb species, official (Rheum officinale, R. palmatum, and R.
      tanguticum) and unofficial (R. franzenbachii, R. hotaoense, and R. emodi), a
      total of 107 phenolic compounds were identified or tentatively characterized
      based on their mass spectra. These compounds include sennosides, anthraquinones,
      stilbenes, glucose gallates, naphthalenes, and catechins. Ion chromatograms for
      the identified compounds of different rhubarbs were then compared. Consistent
      with previous reports, sennosides and rhein were only detected in official
      rhubarbs. Unexpectedly, we found that R. officinale contained very different
      phenolic compounds from the other two official species. Sennoside A, which has
      been considered as the major purgative component of rhubarb, was only detected in
      R. officinale, while its close isomers were observed in R. palmatum and R.
      tanguticum. In addition, the predominant anthraquinone glycosides in R.
      officinale were found to be rhein 8-O-glucoside and emodin 1-O-glucoside, whereas
      those in R. palmatum and R. tanguticum were rhein 1-O-glucoside and emodin 8-O
      glucoside. Stilbenes, which are the major constituents of unofficial rhubarbs,
      were also different among the species. Our results clarify the chemical
      composition of rhubarbs comprehensively for the first time. Due to the
      significant differences in chemical components of rhubarbs, we suggest that
      different Rheum species be used separately in clinical practice.

PMID- 17029979
TI  - A functional single nucleotide polymorphism in the vitamin-K-dependent gamma
      glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in
      elderly Japanese women.
AB  - The vitamin-K-dependent gamma-glutamyl carboxylase (GGCX) carboxylates vitamin-K
      dependent proteins including bone Gla protein (osteocalcin) and matrix Gla
      protein, which play important roles in bone metabolism. Therefore, GGCX
      polymorphism might explain in part individual susceptibility to osteoporosis. In
      the present study, polymorphisms in the exons of this gene were screened in
      Japanese elderly women and a non-synonymous single nucleotide polymorphisms (SNP)
      were found; c.8762 G>A; (Arg325Gln). When the kinetic parameters of GGCX325-Gln
      and GGCX325-Arg were compared in vitro, Vmax/Km was significantly higher for
      GGCX325-Gln (944.4+/-9.21 pmol/30 min/mg/mM FLEEL) than for GGCX325-Arg
      (671.9+10.79 pmol/30 min/mg/mM FLEEL) (p=0.018). Then, association study of this
      polymorphism with forearm bone mineral density (BMD) of Japanese postmenopausal
      women (n=500, age 73.6+/-5.74) was conducted. As a result, the body mass index
      (BMI)-adjusted Z score in the subpopulation older than 75 years (n=207) was
      higher in those with 325-Gln (0.650+/-0.883, mean+/-SD) than those with 325
      Arg/Gln or 325-Arg (0.133+/-0.650) (p=0.0383). This is the first report to
      demonstrate the different activities of GGCX between the common genotypes and
      their association with BMD.

PMID- 17029980
TI  - Nuclear factor E2 p45-related factor 2 negatively regulates chondrogenesis.
AB  - The transcription factor nuclear factor E2 p45-related factor 2 (Nrf2) forms
      heterodimers with small musculoaponeurotic fibrosarcoma (Maf) proteins for the
      selective recognition of the antioxidant responsive element on target genes,
      followed by the regulation of gene expression of phase II detoxifying enzymes as
      well as oxidative-stress-inducible proteins in different tissues. In the present
      study, we investigated the role of Nrf2 in the regulation of chondrocyte
      differentiation as well as the expression pattern of Nrf2 in cartilage. In tibia
      from embryonic mice at E15.5, Nrf2 mRNA expression was restricted to both
      proliferating and pre-hypertrophic chondrocytes, with few signals in early and
      late hypertrophic chondrocytes expressing both type X collagen and osteopontin.
      On in situ hybridization analysis of tibia from neonatal mice at 1 day after
      birth, by contrast, Nrf2 was expressed in all chondrocytic layers in addition to
      osteoblasts attached to cancellous bone. In pre-chondrogenic cell line ATDC5
      cells, furthermore, expression of Nrf2 mRNA was also confirmed together with mRNA
      expression of the Kelch-like ECH associating protein 1 and small Maf proteins. In
      ATDC5 cells stably transfected with Nrf2, significant inhibition was seen in the
      differentiation-dependent induction of alkaline phosphatase and increase in the
      Alcian blue staining intensity. Furthermore, stable overexpression of Nrf2
      significantly decreased mRNA expression of several chondrocyte differentiation
      markers such as type II collagen, type X collagen and osteopontin. These data
      suggest that Nrf2 may be a negative regulator of the cellular differentiation
      toward maturation in chondrocytes.

PMID- 17029982
TI  - Semaphorin 6C leads to GSK-3-dependent growth cone collapse and redistributes
      after entorhino-hippocampal axotomy.
AB  - We studied the changes in the distribution of a specific variant of Semaphorin
      Y/6C (Sema6C) in mouse forebrain after axotomy of the entorhino-hippocampal
      perforant pathway. We found this isoform to be widely expressed during
      development, remaining in the adult and showing variations in distribution when
      the perforant pathway was axotomized. These changes were detected in both the
      hippocampal and entorhinal cortices. Sema6C1 immunoreactivity (IR) was high in
      the stratum radiatum of the hippocampus proper and the inner molecular layer of
      the dentate gyrus; the entorhinal cortex showed Sema6C1 IR in both cell bodies
      and in fibers of the II/III and V/VI layers. In axotomized animals, the IR of the
      ipsilateral, but not the contralateral, hemisphere showed that IR had moved into
      the stratum lacunosum-moleculare, the medial molecular layer of the dentate gyrus
      and the fibers, but not the cell bodies, of the entorhinal cortex. These results
      were not reproduced after lateral axotomy of the fimbria fornix, indicating a
      specific role for Sema6C variants in the generation and/or stability of entorhino
      hippocampal synapses. Growth cone collapse of entorhinal and pyramidal neurons,
      as well as activation of glycogen synthase kinase-3 (GSK-3) through depletion of
      the inactive pool, induced by diffusible Sema6C1 further supports this view.

PMID- 17029981
TI  - BDNF up-regulates alpha7 nicotinic acetylcholine receptor levels on
      subpopulations of hippocampal interneurons.
AB  - In the hippocampus, brain-derived neurotrophic factor (BDNF) regulates a number
      of synaptic components. Among these are nicotinic acetylcholine receptors
      containing alpha7 subunits (alpha7-nAChRs), which are interesting because of
      their relative abundance in the hippocampus and their high relative calcium
      permeability. We show here that BDNF elevates surface and intracellular pools of
      alpha7-nAChRs on cultured hippocampal neurons and that glutamatergic activity is
      both necessary and sufficient for the effect. Blocking transmission through NMDA
      receptors with APV blocked the BDNF effect; increasing spontaneous excitatory
      activity with the GABA(A) receptor antagonist bicuculline replicated the BDNF
      effect. BDNF antibodies blocked the BDNF-mediated increase but not the
      bicuculline one, consistent with enhanced glutamatergic activity acting
      downstream from BDNF. Increased alpha7-nAChR clusters were most prominent on
      interneuron subtypes known to directly innervate excitatory neurons. The results
      suggest that BDNF, acting through glutamatergic transmission, can modulate
      hippocampal output in part by controlling alpha7-nAChR levels.

PMID- 17029983
TI  - Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a
      Dcc-independent way.
AB  - Few studies have addressed the issue of how GABAergic interneurons in the
      cerebellar cortex migrate or what guidance cues steer them. Recent data show that
      their development starts at the cerebellar germinal epithelium on top of the
      fourth ventricle. These interneurons continue to proliferate in the postnatal
      cerebellar white matter and later migrate to their final position in the
      cerebellar cortex. Here we report the chemorepulsive action of Netrin1 on
      postnatal cerebellar interneurons in vitro and also show the expression pattern
      of Netrin1 and its receptors Dcc and Unc5. Our expression results further suggest
      that Netrin1 is involved in the migration of GABAergic interneurons in vivo.
      Moreover, our data point to Bergmann glial fibers as possible tracks for these
      cells en route to the molecular layer. Finally, experiments using blocking
      antibodies allow us to conclude that Dcc, although expressed by postnatal
      cerebellar interneurons, is not involved in the repulsive response triggered by
      Netrin1 in these cells.

PMID- 17029984
TI  - Cloning and overexpression of antifungal barley chitinase gene in Escherichia
      coli.
AB  - Plant chitinases are pathogenesis-related proteins, which are believed to be
      involved in plant defense responses to pathogen infection. In this study,
      chitinase gene from barley was cloned and overexpressed in Escherichia coli.
      Chitinase (35 kDa) was isolated and purified. Since the protein was produced as
      insoluble inclusion bodies, the protein was solubilized and refolded. Purified
      chitinase exerted broad-spectrum antifungal activity against Botrytis cinerea
      (blight of tobacco), Pestalotia theae (leaf spot of tea), Bipolaris oryzae (brown
      spot of rice), Alternaria sp. (grain discoloration of rice), Curvularia lunata
      (leaf spot of clover) and Rhizoctonia solani (sheath blight of rice). Due to the
      potential of broad-spectrum antifungal activity barley chitinase gene can be used
      to enhance fungal-resistance in crop plants such as rice, tobacco, tea and
      clover.

PMID- 17029985
TI  - Implementation and performance evaluation of reconstruction algorithms on
      graphics processors.
AB  - The high-throughput needs in electron tomography and in single particle analysis
      have driven the parallel implementation of several reconstruction algorithms and
      software packages on computing clusters. Here, we report on the implementation of
      popular reconstruction algorithms as weighted backprojection, simultaneous
      iterative reconstruction technique (SIRT) and simultaneous algebraic
      reconstruction technique (SART) on common graphics processors (GPUs). The speed
      gain achieved on the GPUs is in the order of sixty (60x) to eighty (80x) times,
      compared to the performance of a single central processing unit (CPU), which is
      comparable to the acceleration achieved on a medium-range computing cluster. This
      acceleration of the reconstruction is caused by the highly specialized
      architecture of the GPU. Further, we show that the quality of the reconstruction
      on the GPU is comparable to the CPU. We present detailed flow-chart diagrams of
      the implementation. The reconstruction software does not require special hardware
      apart from the commercially available graphics cards and could be easily
      integrated in software packages like SPIDER, XMIPP, TOM-Package and others.

PMID- 17029986
TI  - Neural correlates of memory confidence.
AB  - The present study aimed to shed light on the neural underpinnings of high vs. low
      memory confidence. To dissociate memory confidence from accuracy, the Deese
      Roediger McDermott (DRM) paradigm was employed, which - compared to other memory
      paradigms - elicits a rather evenly distributed number of high-confident
      responses across all possible combinations of memory response types (i.e., hits,
      false alarms, correct rejections, and misses). In the standard DRM procedure,
      subjects are first presented with thematically interrelated word lists at
      encoding, which at recognition are intermixed with related and unrelated
      distractor items. The signature of a false memory or DRM effect is an increased
      number of high-confident false memories, particularly for strongly related lure
      items. For the present study, 17 female subjects were administered a verbal DRM
      task, whereas neural activation was indexed by fMRI. The behavioral analyses
      confirmed the expected false memory effect: subjects made more high-confident old
      responses (both hits and false alarms) the closer the items were related to the
      central list theme. Across all four memory response types, an increase in
      confidence at recognition was associated with bilateral activation in the
      anterior and posterior cingulate cortex along with medial temporal regions. In
      contrast, increments in doubt were solely related to activation in the superior
      posterior parietal cortex. To conclude, the study provides some evidence for
      dissociable systems for confidence and doubt.

PMID- 17029987
TI  - Sources of systematic bias in hypercapnia-calibrated functional MRI estimation of
      oxygen metabolism.
AB  - The change in cerebral rate of oxidative metabolism (CMR(O(2))) during neural
      activation may be estimated from blood oxygenation level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) and arterial spin-labeling (ASL)
      fMRI measurements. The established method relies on an epoch of iso-metabolic
      blood flow increase, typically induced by CO2 breathing, to calibrate the BOLD
      CBF relationship at resting-state CMR(O2). Here, we discuss the systematic bias
      in CMR(O2)-CBF data that can be introduced depending on the value derived for the
      calibration constant (M) from the CO2 breathing epoch. We demonstrate that the
      fidelity of BOLD-CBF data acquired during the neural activation task have low
      impact on the tightness of CMR(O2)-CBF coupling, as well as the coupling slope,
      when the derived calibration value is of a relatively moderate amplitude (M in
      the range of, or greater than, 10-15 at 1.5 T). Via the standard reformulation of
      a grid in BOLD-CBF space into the CMR(O2)-CBF plane, we demonstrate the non
      linear transformation that takes place and the sources of systematic bias that
      result. We find that the outcome of a neurovascular coupling study may be
      predicted to a large extent purely from the value of the calibration constant, M,
      that is used. Our results suggest that the accurate determination of M is of
      greater importance than thought previously and indicate that BOLD-CBF data must
      always be supplied when considering CMR(O2)-CBF behavior in a particular brain
      region.

PMID- 17029988
TI  - Inverse retinotopy: inferring the visual content of images from brain activation
      patterns.
AB  - Traditional inference in neuroimaging consists in describing brain activations
      elicited and modulated by different kinds of stimuli. Recently, however,
      paradigms have been studied in which the converse operation is performed, thus
      inferring behavioral or mental states associated with activation images. Here, we
      use the well-known retinotopy of the visual cortex to infer the visual content of
      real or imaginary scenes from the brain activation patterns that they elicit. We
      present two decoding algorithms: an explicit technique, based on the current
      knowledge of the retinotopic structure of the visual areas, and an implicit
      technique, based on supervised classifiers. Both algorithms predicted the
      stimulus identity with significant accuracy. Furthermore, we extend this
      principle to mental imagery data: in five data sets, our algorithms could
      reconstruct and predict with significant accuracy a pattern imagined by the
      subjects.

PMID- 17029989
TI  - Behavioral alterations in mice lacking the translation repressor 4E-BP2.
AB  - The requirement for de novo protein synthesis during multiple forms of learning,
      memory and behavior is well-established; however, we are only beginning to
      uncover the regulatory mechanisms that govern this process. In order to determine
      how translation initiation is regulated during neuroplasticity we engineered
      mutant C57Bl/6J mice that lack the translation repressor eukaryotic initiation
      factor 4E-binding protein 2 (4E-BP2) and have previously demonstrated that 4E-BP2
      plays a critical role in hippocampus-dependent synaptic plasticity and memory.
      Herein, we examined the 4E-BP2 knockout mice in a battery of paradigms to address
      motor activity and motor skill learning, anxiety and social dominance behaviors,
      working memory and conditioned taste aversion. We found that the 4E-BP2 knockout
      mice demonstrated altered activity in the rotating rod test, light/dark
      exploration test, spontaneous alternation T-maze and conditioned taste aversion
      test. The information gained from these studies builds a solid foundation for
      future studies on the specific role of 4E-BP2 in various types of behavior, and
      for a broader, more detailed examination of the mechanisms of translational
      control in the brain.

PMID- 17029990
TI  - Granulocyte and granulocyte macrophage colony-stimulating factors as therapy in
      human and veterinary medicine.
AB  - Granulocyte colony-stimulating factors (G-CSFs) and granulocyte macrophage colony
      stimulating factors (GM-CSFs) are endogenous cytokines that regulate granulocyte
      colonies and play a major role in the stimulation of granulopoiesis (neutrophils,
      basophils and eosinophils) and in the regulation of microbicidal functions. There
      are numerous pathological conditions in which neutrophils are decreased, the most
      common being neutropenia associated with cancer chemotherapy, which increases the
      risk of serious microbial infections developing with the potential for high
      morbidity and mortality. New methods in molecular biology have led to the
      identification and cloning of CSF genes and biopharmaceutical production. Since
      then, CSFs have been widely used for the prevention and treatment of neutropenia
      associated with cancer chemotherapy, for mobilising haematopoietic cell
      precursors, and for other neutropenia-related pathologies. This review focuses on
      the use of CSFs within both human and veterinary medicine. Clinical applications,
      pharmacology, tolerability and the potential role of these factors in veterinary
      medicine are considered.

PMID- 17029991
TI  - Paediatric and adult ataxias (update 5).

PMID- 17029992
TI  - Current density imaging by pulsed conduction electron spin resonance.
AB  - In analogy with Nuclear MRI, the ESR signal phase shift of conduction electrons
      moving in electrical currents along controlled magnetic field gradients can be
      used to generate spatial electronic current density maps. First two-dimensional
      images of the current density distribution in quasi-one-dimensional organic
      conductors are presented.

PMID- 17029993
TI  - In vitro estimates of power output by epaxial muscle during feeding in largemouth
      bass.
AB  - Recent work has employed video and sonometric analysis combined with hydrodynamic
      modeling to estimate power output by the feeding musculature of largemouth bass
      in feeding trials. The result was an estimate of approximately 69 W kg(-1) of
      power by the epaxial muscle during maximal feeding strikes. The present study
      employed in vitro measurements of force, work and power output by fast-twitch
      epaxial muscle bundles stimulated under activation conditions measured in vivo to
      evaluate the power output results of the feeding experiments. Isolated muscle
      bundles from the epaxial muscle, the sternohyoideus and the lateral red or slow
      twitch muscle were tied into a muscle mechanics apparatus, and contractile
      properties during tetanic contractions and maximum shortening velocity (Vmax)
      were determined. For the epaxial muscles, work and power output during feeding
      events was determined by employing mean stimulation conditions derived from a
      select set of maximal feeding trials: 17% muscle shortening at 3.6 muscle
      lengths/s, with activation occurring 5 ms before the onset of shortening. Epaxial
      and sternohyoideus muscle displayed similar contractile properties, and both were
      considerably faster (Vmax approximately 11-13 ML s(-1)) than red muscle (Vmax
      approximately 5 ML s(-1)). Epaxial muscle stimulated under in vivo activation
      conditions generated approximately 60 W kg(-1) with a 17% strain and
      approximately 86 W kg(-1) with a 12% strain. These values are close to those
      estimated by hydrodynamic modeling. The short lag time (5 ms) between muscle
      activation and muscle shortening is apparently a limiting parameter during
      feeding strikes, with maximum power found at an offset of 15-20 ms. Further,
      feeding strikes employing a faster shortening velocity generated significantly
      higher power output. Power production during feeding strikes appears to be
      limited by the need for fast onset of movement and the hydrodynamic resistance to
      buccal expansion.

PMID- 17029994
TI  - Egg components, egg size, and hatchling size in leatherback turtles.
AB  - Relationships between egg size, egg components, and neonate size have been
      investigated across a wide range of oviparous taxa. Differences in egg traits
      among taxa reflect not only phylogenetic differences, but also interactions
      between biotic (i.e., maternal resource allocation) and abiotic (i.e. nest
      environment conditions) factors. We examined relationships between egg mass, egg
      composition, and hatchling size in leatherback turtles (Dermochelys coriacea)
      because of the unique egg and reproductive characteristics of this species and of
      sea turtles in general. Albumen comprised 63.0%+/-2.8% (mean+/-S.D.) of egg mass
      and explained most of the variation in egg mass, whereas yolk comprised only
      33.0%+/-2.7%. Additionally, leatherback albumen dry mass was approximately 16% of
      albumen wet mass. Whereas hatchling mass increased significantly with egg mass (n
      = 218 clutches), hatchling mass increased by only approximately 2 g for each 10 g
      increase in egg mass and was approximately 10-20 g greater than yolk mass. Taken
      together, our results indicate that albumen might play a particularly significant
      role in leatherback embryonic development, and that leatherback eggs are both
      capable of water uptake from the nest substrate and also possess a large
      reservoir of water in the albumen. Relationships between egg mass and egg
      components, such as variation in egg mass being largely explained by variation in
      albumen mass and egg mass containing a relatively high proportion of albumen
      solids, are more similar to bird eggs than to eggs of other non-avian reptiles.
      However, hatchling mass correlates more with yolk mass than with albumen mass,
      unlike patterns observed in bird eggs of similar composition.

PMID- 17029995
TI  - Extraction and protein component analysis of venom from the dissected venom
      glands of Latrodectus tredecimguttatus.
AB  - Black widow spiders (genus Latrodectus) have attracted increasing attention due
      to frequently reported human injuries caused by them and the potential
      applications of biologically active components in their venoms. Although a number
      of studies have described the biological properties and structures of several
      venomous proteins such as latrotoxins, a comprehensive analysis of protein
      component of the venom from the spider is not available. We used combinative
      proteomic strategies to assess the protein components of the crude venom
      collected from Latrodectus tredecimguttatus by extracting the dissected venom
      glands. The experiments demonstrated that the crude venom of L. tredecimguttatus
      has a high abundance of acidic proteins with molecular masses greater than 15
      kDa, and the content of proteins and peptides of below 15 kDa is low. 86 unique
      proteins were identified, part of which were contaminations of cellular
      components during the extraction, determined in comparison with venom obtained by
      electrostimulation. Except for members of latrotoxin family that were commonly
      considered as the primary toxic components of the venom, several other special
      enzymes and proteins were detected such as protease, phosphatase, lysozyme,
      inhibitory protein, and so on. These protein components, particularly the
      proteases, were speculated to play important roles in the action of L.
      tredecimguttatus venom.

PMID- 17029996
TI  - Effects of growth hormone and/or testosterone on very low density lipoprotein
      apolipoprotein B100 kinetics and plasma lipids in healthy elderly men: a
      randomised controlled trial.
AB  - OBJECTIVE: To assess the effects of low dose recombinant growth hormone (GH),
      testosterone (T) and combined GH and T, on lipid profiles and very low density
      lipoprotein apolipoprotein B (VLDL apoB) metabolism. DESIGN AND PATIENTS: Sixty
      nine healthy elderly men (65-80 yr) were studied in a six month double-blind,
      placebo-controlled trial. Participants were randomised to placebo GH and placebo
      T (P), GH and placebo T (GH), T and placebo GH (T) or GH and T (GHT).
      MEASUREMENTS: Plasma lipid profiles were assessed before treatment and at 6
      months. VLDL apoB absolute secretion rate (ASR) and fractional catabolic rate
      (FCR) were measured in a subset of 21 men: P (n=5); GH (n=5); T (n=6); GHT (n=5),
      with an infusion of 1-(13)C leucine. Fat mass (FM) was measured by DEXA and intra
      abdominal fat (IAF) by CT scan. RESULTS: IGF-I levels increased in the GH and GHT
      (P<0.001) groups: testosterone increased in the T (P=0.029) and GHT (P=0.05)
      groups. There was no change in total cholesterol, LDL-cholesterol, HDL
      cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B or
      lipoprotein(a) in the GH, GHT or T groups. In the subset of 21 men, IGF-I levels
      increased similarly with GH and GHT (P<0.01) but T levels increased only with T
      (P<0.03). FM and IAF decreased significantly only with GHT (P<0.01, P=0.01).
      Treatment with GH, T or GHT had no effect on VLDL apoB ASR or VLDL FCR.
      CONCLUSION: Co-administration of GH and T in near physiological doses in healthy
      elderly men resulted in favourable changes in body composition without altering
      the plasma lipid profile or VLDL apoB metabolism.

PMID- 17029997
TI  - A failure of resilience: estimating response of New York City's public health
      ecosystem to sudden disaster.
AB  - Adapting methodology from resilience theory in ecology, we develop an empirical
      model of the response of the New York City public health ecosystem to sudden
      disaster. Contrary to cultural expectation, 'good' and 'bad' neighborhoods
      starkly differentiated by public health status reflecting longstanding economic
      and racial segregation-respond similarly to challenge. This suggests that the
      difference in health between neighborhoods is primarily predicated on the extent
      to which they have been, and continue to be, exposed to differing patterns of
      stressors and affordances, rather than to any difference in underlying socio
      economic vulnerability. Paradoxically, then, these urban neighborhoods constitute
      a single, highly interdependent, health ecosystem, despite substantial
      socioeconomic and racial segregation.

PMID- 17029998
TI  - VISA--a pass to innate immunity.
AB  - Virus-induced signaling adaptor (VISA) is essential for host innate immune
      responses against double-stranded RNA viral infection and viral replication. It
      is an adaptor that activates the transcription factors nuclear factor kappaB (NF
      kappaB) and interferon regulatory factor 3 (IRF3) that regulate the expression of
      type I interferons. The localization of VISA to the outer membrane of
      mitochondria and the cellular consequences of its activation implicate this
      protein in the cellular etiology of neurodegenerative disorders.

PMID- 17029999
TI  - Streptococcus pyogenes: Insight into the function of the streptococcal
      superantigens.
AB  - The group A streptococcus produces a number of highly potent exoproteins that act
      as superantigens. The cascade of pro-inflammatory events that follow invasive
      streptococcal infection is greatly enhanced by production of such toxins, leading
      to profound hypotension and multi-organ failure in some cases. Superantigens such
      as streptococcal mitogenic exotoxin Z (SMEZ) interact with host MHC class II and
      the T cell receptor, leading to activation events in both cells. In vitro, these
      interactions lead to expansion and cytokine production by specified T cell
      subsets. Studies using humanized HLA class II transgenic mice and isogenic
      streptococcal strains have characterised the in vivo responses to superantigens
      produced in the context of live infection. Notwithstanding the obvious
      deleterious role of superantigens in toxic shock, the evolutionary advantage
      conferred by these toxins remains a subject of speculation.

PMID- 17030000
TI  - An in vitro method for selective detection of free monomeric ubiquitin by using a
      C-terminally biotinylated form of ubiquitin.
AB  - In an effort to design a selective assay allowing detection of free monomeric
      ubiquitin, an approach based on a C-terminally biotinylated form of ubiquitin is
      proposed. In the form of a polyubiquitin chain, ubiquitin marks proteins for
      degradation by the 26S proteasome. This covalently attached signal is assembled
      from multiple ubiquitins linked to each other via the C-terminus of one ubiquitin
      and the epsilon-amine of Lys48 of another ubiquitin. In the present study, a form
      of ubiquitin having the C-terminus modified with the addition of a biotinylation
      peptide tag was prepared. After expression, this modified ubiquitin was
      biotinylated in vitro using recombinant biotin ligase. Biotinylated ubiquitin was
      further purified using affinity chromatography on immobilized monovalent avidin.
      This tagged form of ubiquitin is blocked at the C-terminus and therefore can only
      act as an acceptor (Lys-48 donor) in polyubiquitin chain synthesis. In vitro
      enzymatic assembly of multiubiquitin chains from biotinylated monoubiquitin and
      natural monoubiquitin is demonstrated by Western blot analysis using horseradish
      peroxidase-conjugated streptavidin. Data obtained with this assay indicate
      potential uses of the C-terminally biotinylated form of ubiquitin for selective
      detection of monoubiquitin contamination in a cell extract experimentally
      depleted of ubiquitin, i.e. lysate Fraction II. Cell-free systems established for
      in vitro examination of ubiquitin involvement in proteolytic processes usually
      employ Fraction II, which should be essentially ubiquitin-free. It is suggested
      that the assay using biotinylated monoubiquitin can be useful to exclude the
      possibility that ubiquitin contamination of laboratory prepared lysate Fraction
      II accounts for protein degradation in this fraction.

PMID- 17030001
TI  - Effects of the single point genetic mutation D54G on muscle creatine kinase
      activity, structure and stability.
AB  - Aberrant folding of important proteins caused by genetic mutations is closely
      correlated to many diseases. Due to the important physiological role in excitable
      cells, the activity and level of creatine kinase (CK) play a crucial role in
      maintaining body functions. Muscle CK deficiency disease was identified by an
      unusual CK activity decrease in an acute myocardial infarction patient caused by
      the single point mutation D54G. In this research, it was found that the D54G
      mutant had substantially decreased activity, substrate binding affinity and
      stability. Spectroscopic experiments indicated that the mutation impaired the
      structure of CK, which resulted in a partially unfolded state with more
      hydrophobic exposure and exposed Trp residues. The inability to fold to the
      functional compact state made the mutant be prone to aggregate upon
      microenvironmental stresses, and might gradually decrease the CK level of the
      patient.

PMID- 17030002
TI  - Interleukin-22: a novel T- and NK-cell derived cytokine that regulates the
      biology of tissue cells.
AB  - Interleukin (IL)-22, discovered in 2000, is a member of the IL-10 family of
      cytokines. The major sources of IL-22 are activated T1- and NK-cells. IL-22 acts
      via a heterodimeric receptor complex consisting of IL-22R1 and IL-10R2. Neither
      resting nor activated immune cells express IL-22R1 or respond to IL-22. In
      contrast, tissue cells at outer body barriers, i.e. of the skin, kidney, and the
      digestive and respiratory systems are targets of this cytokine. IL-22 functions
      by promoting the anti-microbial defense, protecting against damage, and re
      organizing non-immune tissues. Furthermore, IL-22 induces acute phase reactants.
      These findings indicate that IL-22 represents a novel type of immune mediator
      that, although produced by immune cells, regulates tissue protection and
      homeostasis.

PMID- 17030003
TI  - Peptide-based fibrous biomaterials: Some things old, new and borrowed.
AB  - Bioinspired fibrous materials that span the nano-to-meso scales have potentially
      broad applications in nanobiotechnology; for instance, as scaffolds in 3D cell
      culture and tissue engineering, and as templates for the assembly of other
      polymer and inorganic materials. The field is burgeoning, and this review is
      necessarily focused. It centres on recent developments in the design of peptide
      based fibres and particularly those using the alpha-helix and the collagen triple
      helix as building blocks for self-assembly. Advances include new designs in both
      categories, the assembly of more-complex topologies using fibres themselves as
      building blocks, and the decoration of the assembled materials with functional
      moieties.

PMID- 17030005
TI  - Nature of water in nacre: a 2D Fourier transform infrared spectroscopic study.
AB  - In this work, the interactions of aragonite and organic matrix in nacre with
      water are investigated using two-dimensional (2D) Fourier transform infrared
      (FTIR) spectroscopy. The 2D-FTIR analysis revealed four bands in the OH
      stretching region at around 3550, 3445, 3272 and 3074 cm(-1). Two additional
      bands were found at around 3616 and 3282 cm(-1) after deconvolution of the nacre
      spectrum. The bands at around 3616 and 3550 cm(-1) are assigned to asymmetric and
      symmetric OH stretching of partially hydrogen bonded water molecules. The bands
      at around 3445 and 3272 cm(-1) are assigned to asymmetric and symmetric OH
      stretching of water molecules fully hydrogen bonded with surrounding water
      molecules. Presence of above bands in the nacre spectrum suggests that water, in
      form of clusters, is present in protein matrix and aragonite pores. Water may
      also hydrogen bond with the organic matrix. The bands observed at 3282 and 3074
      cm(-1) are assigned to asymmetric and symmetric OH stretching of water molecules,
      chemisorbed on surfaces of aragonite platelets. Polarization experiments suggest
      that H-O-H plane of water molecules is along to c-axis of aragonite platelets.

PMID- 17030006
TI  - Development of an optode membrane for high pH values.
AB  - The development of an optical pH sensor for high pH values is described based on
      the immobilization of Aniline Blue on an optically transparent triacetylcellulose
      membrane. The membrane is useful for repetitive and reversible pH measurements in
      the pH range of 8.8-13. The relative standard deviation is about 1.6% and 2% for
      seven measurements of the maximum change at 579 nm from pH 9 to 10.8 and from pH
      11.1 to 12.8, respectively. Other advantages of the sensor include rapid
      equilibration time, long term stability, reversibility, high sensitivity, freedom
      from interference of other cations and ease of fabrication.

PMID- 17030007
TI  - Theoretical studies on electrochemistry of p-aminophenol.
AB  - Geometric parameters, vibrational frequencies and thermochemical values of p
      quinonimine (p-Q) and p-aminophenol (p-AP) were computed by ab initio calculation
      (HF) and density function theory (DFT) with the 6-31G(d,p) basis set. Cyclic
      voltammetry with a goldren electrode of p-AP solutions in phosphate buffers at pH
      7.30 showed that standard electrode potential of half reaction for (p-Q) and (p
      AP) is 0.728V. Standard electrode potential of half reaction for p-Q and p-AP
      were calculated using the sum of electronic and thermal free energies of p-Q and
      p-AP with normal hydrogen electrode (NHE) as a reference electrode. The results
      show that the theoretical standard electrode potential of half reaction for p-Q
      and p-AP is 0.682V at B3LYP/6-31G(d,p) level and 0.622V at HF/6-31G(d,p) level,
      respectively, indicating that computed standard electrode potential at B3LYP/6
      31G(d,p) level are more reliable than that at HF/6-31G(d,p) level.

PMID- 17030008
TI  - Mass spectrometric investigation of buspirone drug in comparison with thermal
      analyses and MO-calculations.
AB  - The buspirone drug is usually present as hydrochloride form of general formula
      C(21)H(31)N(5)O(2).HCl, and of molecular weight (MW)=421.96. It is an analgesic
      anxiolytic drug, which does not cause sedative or depression of central nervous
      system. In the present work it is investigated using electron impact mass
      spectral (EI-MS) fragmentation at 70 eV, in comparison with thermal analyses (TA)
      measurements (TG/DTG and DTA) and molecular orbital calculation (MOC). Semi
      empirical MO calculation, PM3 procedure, has been carried out on buspirone both
      as neutral molecule (in TA) and the corresponding positively charged species (in
      MS). The calculated MOC parameters include bond length, bond order, particle
      charge distribution on different atoms and heats of formation. The fragmentation
      pathways of buspirone in EI-MS lead to the formation of important primary and
      secondary fragment ions. The mechanism of formation of some important daughter
      ions can be illuminated from comparing with that obtained using electrospray
      ESIMS/MS mode mass spectrometer through the accurate mass measurement
      determination. The losses of the intermediate aliphatic part (CH2)4 due to
      cleavage of N-C bond from both sides is the primary cleavage in both techniques
      (MS and TA). The PM3 provides a base for fine distinction among sites of initial
      bond cleavage and subsequent fragmentation of drug molecule in both TA and MS
      techniques; consequently the choice of the correct pathway of such fragmentation
      knowing this structural session of bonds can be used to decide the active sites
      of this drug responsible for its chemical, biological and medical reactivity.

PMID- 17030009
TI  - Structure elucidation of laser dye coumarin-540A by joint application of X-ray
      diffraction, X-ray fluorescence, prompt fluorescence, UV and visible
      spectroscopy.
AB  - X-ray, ultraviolet, and visible light induced photophysical changes of coumarin
      540A in ethanol have been studied by the joint applications of X-ray,
      ultraviolet, and visible spectroscopy. Some impurities were found by X-ray
      fluorescence measurements. During the high power optical pumping, coumarin showed
      photochemical changes. Photoproduct emission spectra characteristics showed that
      photoproduct molecules can also be used as a laser dye at a different emission
      frequency in the ultraviolet region.

PMID- 17030011
TI  - Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood
      cells obtained from patients with chronic hepatitis C.
AB  - The global transcriptional profile during the first 4 weeks of treatment with
      pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC)
      was evaluated. cDNA array technology was used to assess expression of 10,918
      human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7,
      and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average
      linkage clustering identified seven temporal profiles of differential expression
      comprising 148 genes. Gene expression profiles were comparable between the PEG
      IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of
      molecular functions were differentially regulated with distinct temporal patterns
      of expression. The initial global response to interferon treatment appears to be
      a net up-regulation of genes, consistent with gene responses identified
      previously in vitro, though by 4 weeks an overall down-regulation of genes was
      observed. Novel transcription factors potentially involved in secondary gene
      regulation cascades, a potential dsRNA receptor and members of the ubiquitin
      signaling, including a novel predicted deubiquitinating peptidase were all
      identified as being up-regulated upon treatment with IFN. The overall findings
      provide new light on possible physiological effects of IFN-alpha and open new
      lines of investigations on the mode of action of PEG-IFN-alpha combination
      therapy.

PMID- 17030010
TI  - Optical characterization of Sm3+ and Dy3+:ZnO-PbO-B2O3 glasses.
AB  - Here, we present the results of the analysis of Sm(3+) or Dy(3+) (0.5 mol%) ions
      doped heavy metal oxide (HMO)-based zinc lead borate (ZLB) glasses. Optical
      measurements such as absorption, emission spectra, lifetimes, XRD, DSC profiles
      have been carried out. The emission spectrum of Sm(3+):ZLB has shown the emission
      transitions of (4)G(5/2)-->(6)H(5/2) (563 nm), (4)G(5/2)-->(6)H(7/2) (598 nm),
      (4)G(5/2)-->(6)H(9/2) (646 nm), (4)G(5/2)-->(6)H(11/2) (708 nm) with lambda(exc):
      401 nm ((6)H(5/2)-->(4)F(7/2)). In the case of the Dy(3+):ZLB glass, emission
      transitions of (4)F(9/2)-->(6)H(15/2) (485 nm), (4)F(9/2)-->(6)H(13/2) (575 nm)
      and (4)F(9/2)-->(6)H(11/2) (664 nm) with lambda(exi): 447 nm ((6)H(15/2)-
      >(4)I(15/2)) have been identified. Energy level schemes relating to the emission
      mechanisms involved in Sm(3+) and Dy(3+) glasses have been given.

PMID- 17030012
TI  - The t-CWT: a new ERP detection and quantification method based on the continuous
      wavelet transform and Student's t-statistics.
AB  - OBJECTIVE: This study was aimed at developing a method for extraction and
      assessment of event-related brain potentials (ERP) from single-trials. This
      method should be applicable in the assessment of single persons' ERPs and should
      be able to handle both single ERP components and whole waveforms. METHODS: We
      adopted a recently developed ERP feature extraction method, the t-CWT, for the
      purposes of hypothesis testing in the statistical assessment of ERPs. The t-CWT
      is based on the continuous wavelet transform (CWT) and Student's t-statistics.
      The method was tested in two ERP paradigms, oddball and semantic priming, by
      assessing individual-participant data on a single-trial basis, and testing the
      significance of selected ERP components, P300 and N400, as well as of whole ERP
      waveforms. The t-CWT was also compared to other univariate and multivariate ERP
      assessment methods: peak picking, area computation, discrete wavelet transform
      (DWT) and principal component analysis (PCA). RESULTS: The t-CWT produced better
      results than all of the other assessment methods it was compared with.
      CONCLUSIONS: The t-CWT can be used as a reliable and powerful method for ERP
      component detection and testing of statistical hypotheses concerning both single
      ERP components and whole waveforms extracted from either single persons' or group
      data. SIGNIFICANCE: The t-CWT is the first such method based explicitly on the
      criteria of maximal statistical difference between two average ERPs in the time
      frequency domain and is particularly suitable for ERP assessment of individual
      data (e.g. in clinical settings), but also for the investigation of small and/or
      novel ERP effects from group data.

PMID- 17030013
TI  - Seizures and adverse events during routine scalp electroencephalography: a
      clinical and EEG analysis of 1000 records.
AB  - OBJECTIVE: To quantify the incidence of seizures and adverse events during
      standard electroencephalography (EEG). METHODS: A retrospective random sample of
      1000 of a total of 3391 reports of standard scalp EEG recordings during 2002 at
      Kings College Hospital were studied, and adverse events during standard EEG were
      recorded. Photic induced seizures and epileptiform activity were compared with
      the resting, hyperventilation and sleep EEG. RESULTS: Adverse events occurred in
      131 records (13.1%), including seizures in 60 records (45 electro-clinical and 15
      non-epileptic seizures). The overall incidence of electro-clinical seizures was
      not statistically different during the resting EEG (2.8%), sleep EEG (2%),
      hyperventilation EEG (2.1%) and during photic stimulation EEG (1.4%). There was a
      higher frequency of electro-clinical seizures during hyperventilation and sleep
      in those with a diagnosis of idiopathic generalised epilepsy (31.5%) and during
      photic stimulation in photosensitive patients (31%). The incidence of electro
      clinical seizures was significantly less during activation procedures in focal
      epilepsies (2.6%). Activation techniques made a unique diagnostic contribution
      when routine resting EEG was normal or equivocal in 11% of cases. CONCLUSIONS:
      Adverse events occurred in 13.1% of records, and most were minor. Sixty of the
      adverse events were seizures. Those generated during the EEG were brief and
      safety precautions operated successfully. In those without a prior diagnosis, the
      chance of seizures is the same during both resting and activation EEG. In those
      patients with generalised epilepsy or photosensitivity, activation procedures
      have a higher rate of seizure induction. SIGNIFICANCE: This study has
      implications for informed consent for EEG.

PMID- 17030014
TI  - A high prevalence of sleep disordered breathing in men with mild symptomatic
      chronic heart failure due to left ventricular systolic dysfunction.
AB  - BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart
      failure (CHF) and is associated with increased morbidity and mortality. The
      prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study
      was to determine the prevalence and characteristics of SDB in male patients with
      NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild
      symptomatic CHF underwent assessment of quality of life, echocardiography,
      cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the
      patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive
      sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile
      range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced
      chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs.
      1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher
      levels of brain natriuretic peptide and endothelin-1 compared to patients without
      SDB. No differences in left ventricular ejection fraction, percent predicted peak
      oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence
      of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be
      differentiated by symptoms or by routine cardiac assessment making clinical
      diagnosis of SDB in CHF difficult.

PMID- 17030015
TI  - Involvement of insulin-like growth factor-I in the control of glucose
      homeostasis.
AB  - Insulin-like growth factor-I (IGF-I) has significant structural homology with
      proinsulin. IGF-I binds to insulin receptors, stimulates insulin-like actions and
      enhances insulin sensitivity. However, because circulating IGF-I is bound to high
      affinity binding proteins and has relatively low affinity for insulin receptors,
      most of its ability to alter insulin sensitivity is mediated indirectly (i.e.
      through suppression of growth hormone, a known insulin antagonist). Direct
      effects of IGF-I on insulin actions are tissue specific, occurring principally in
      skeletal muscle and kidney. Genetic manipulations in experimental mouse models
      have been used to analyze the role of endogenous IGF-I on insulin action. These
      studies have shown that suppression of growth hormone is important for enhancing
      insulin action in the liver and that deletion of the IGF-I receptor in skeletal
      muscle results in severe insulin resistance. IGF-I also suppresses renal
      gluconeogenesis, which might contribute to its glucose-lowering actions. In
      humans, IGF-I enhances insulin sensitivity and lowers blood glucose in patients
      with either extreme insulin resistance or type 2 diabetes. It also decreases
      insulin requirement in patients with insulin-deficient diabetes. Taken together,
      these findings suggest that IGF-I is functioning coordinately with insulin to
      regulate glucose homeostasis.

PMID- 17030017
TI  - Transmission control for schistosomiasis - why it matters now.
AB  - Current population-based schistosomiasis treatment programs are a first step to
      reducing the global burden of Schistosoma-related disease; however, they might
      not dramatically reduce parasite transmission in highly endemic areas.
      Consequently, the benefits of these programs remain in doubt because recurring
      low-level reinfection is likely to be associated with subtle but persistent
      morbidities such as anemia, undernutrition and diminished performance status. The
      real health benefits of transmission control need to be reconsidered and
      attention given to more aggressive and, ultimately, more affordable parasite
      elimination strategies. The next generation of schistosomiasis control can be
      optimized using new monitoring tools and effective transmission containment.

PMID- 17030018
TI  - B-cell immune responses in HIV positive and HIV negative patients with
      tuberculosis evaluated with an ELISA using a glycolipid antigen.
AB  - The diagnostic value of the PGL-Tb1 enzyme-linked immunosorbent assays (ELISA)
      was established following a survey study using sera from 220 Tuberculosis
      patients (including 69 HIV coinfected) and 324 controls. A higher percentage
      (76.8%) of the HIV-seropositive compared to the HIV-seronegative (58.9%) TB
      patients were ELISA positive (p=0.02) with a specificity of 94%. In HIV-positive
      TB patients, ELISA sensitivity was identical for all sites of disease and
      antibody levels were not affected by the CD4+ counts, PPD results, age or
      bacterial yield. Combining data for both the smear microscopy and ELISA maximized
      sensitivity. The kinetics of anti-PGL-Tb1 antibody was evaluated in cohort
      studies using sera collected before, during and after treatment for clinical TB
      for 79 TB patients (including 39 HIV coinfected). Statistically significant ELISA
      signals were observed in 51.3% of HIV-seropositive TB patients prior to the
      diagnosis of clinical TB and elevated antibody levels persisting 18 months after
      the end of antituberculous chemotherapy. Asymptomatic development of antibody
      also occurred in 22.7% of a cohort of 44 HIV-positive patients with a high risk
      of tuberculosis, but no correlation was found between persisting elevated
      antibody levels and progression to active disease. This antibody response in
      absence of disease, might reflect the control of an incipient tuberculosis
      infection by antituberculous prophylaxis or through an improved protective immune
      response associated with antiretroviral therapy.

PMID- 17030019
TI  - Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium
      tuberculosis: biosynthesis, transport, regulation and biological activities.
AB  - The cell envelope of pathogenic mycobacteria is highly distinctive in that it
      contains a number of lipids esterified with structurally related long-chain multi
      methyl-branched fatty acids. These lipids have long been thought to play
      important roles in the cell envelope structure as well as in the pathogenicity of
      the tubercle bacillus. This review summarizes what is known about the
      biosynthesis of long-chain multiple methyl-branched fatty acid-containing lipids
      in Mycobacterium tuberculosis and describes the most recent findings about their
      regulation, transport across the different layers of the cell envelope and their
      biological functions.

PMID- 17030021
TI  - Application of tissue Doppler to interpretation of exercise echocardiography:
      diagnostics of ischemia localization in patients with ischemic heart disease.
AB  - Development of optimal methods for the objective non-invasive diagnosis of
      coronary artery disease remains a challenge for imaging techniques in stress
      tests. AIM: The aim of this study was to obtain quantitative diagnostic criteria
      TDI which could detect significant coronary artery disease during exercise
      echocardiography. METHODS AND RESULTS: We evaluated regional systolic and
      diastolic myocardial functions of 123 patients by pulsed wave tissue Doppler
      imaging (TDI) in eight segments of left ventricle during exercise stress testing.
      Diagnostic criteria were obtained by comparing TDI and coronary angiography data.
      Best cut-points of velocity parameters allowed developing two diagnostic models
      for the detection of left anterior descending (LAD) and circumflex (LCx) artery
      diseases. The accuracy of the TDI diagnostic model for LAD-disease was 86.2% and
      for LCx-disease 78.3%. There were no criteria for the detection of RCA disease in
      this study. CONCLUSION: So TDI is a very accurate method for the detection of LAD
      and LCx-disease during exercise stress echocardiography.

PMID- 17030020
TI  - Cardiac hemangioma of the right atrium.
AB  - Primary cardiac tumors are rare, with an incidence range between 0.001% and
      0.030% at autopsy. Recent technical advances have facilitated diagnosis and
      surgical treatment of such lesions. Patients with a resectable tumor usually have
      a good prognosis, but patients with an unresectable tumor may have a poor
      prognosis. This report shows a case of right atrial hemangioma growing like an
      extracardiac mass, with cardiac tamponade the only clinical presentation.

PMID- 17030022
TI  - Spontaneous chordae rupture of tricuspid valve in patient with chronic renal
      failure.
AB  - Spontaneous chordae rupture of the tricuspid valve is relatively rare, unlike the
      mitral valve. We present a 27-year-old male with chronic renal failure on
      hemodialysis therapy for treatment of parathyroid adenoma. The echocardiography
      showed the severe tricuspid regurgitation with chordae rupture which was not
      noted 1 year ago. In addition, the papillary muscle of both mitral and tricuspid
      valve was shortened and calcified extensively. However, in his clinical history,
      the specific causes for chordae rupture, such as chest trauma or endocarditis,
      were not disclosed. It was presumed that dilated right ventricle with volume or
      pressure overloading and secondary hyperparathyroidism are probably responsible
      for the chordae rupture of tricuspid valve.

PMID- 17030023
TI  - Echocardiographic evaluation of mitral tethering for 'chordal cutting' procedure.
AB  - 'Chordal cutting' is a recently proposed surgical option for the treatment of
      functional mitral regurgitation due to leaflet tethering. With this technique the
      surgeon sections second order chordae, restores leaflet's convexity towards the
      left atrium and eliminates mitral incompetence. Preoperative assessment of
      tethering mechanism, degree of leaflet distortion, surface of coaptation, annular
      dilation, origin and quantification of valve incompetence by echocardiographic
      means is essential in indicating this surgical option. Intraoperative
      transesophageal evaluation is crucial to assess the morphology and the absence or
      degree of residual incompetence after procedure.

PMID- 17030024
TI  - Daily rhythms of seizure activity and behavior in a model of atypical absence
      epilepsy.
AB  - We studied daily rhythms of chronic seizure activity and behavior in adult rats
      and mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY) during
      early postnatal development. Chronic atypical absence seizures were verified in
      the AY-treated animals by the presence of spontaneous 5- to 6-Hz slow spike-wave
      discharges (SSWDs) in the neocortex. General behavioral activity, as measured by
      total movements (TM), movement time (MT), ambulatory movement time (AMT), time
      spent in center of arena (CT), jumps (JFP), and rotational behavior (TURNS), were
      continuously recorded under a 12-hour light:12-hour dark photocycle. The average
      SSWD duration in AY-treated rats varied daily, with two peaks occurring at
      approximately dark phase and light phase onset. Mice treated with AY exhibited
      significant increases in all behavioral measures during the light and dark
      phases, with the exception of light-phase CT, which did not differ from that of
      controls. Consequently, the daily rhythm of total behavioral activity (TM)
      exhibited a significantly higher mean oscillation (mesor) and amplitude without
      evidence of phase shift compared with the TM rhythm of controls. The occurrence
      of SSWD activity in the AY model appears to be subject to regulation by
      biological timing mechanisms and, furthermore, associated with motor
      hyperactivity that does not alter the timing of behavioral rhythmicity.

PMID- 17030026
TI  - Proteomic inventory of "anchorless" proteins on the colon adenocarcinoma cell
      surface.
AB  - Surface proteins play important pathophysiological roles in health and disease,
      and accumulating proteomics-based studies suggest that several "non-membrane"
      proteins are sorted to the cell surface by unconventional mechanisms.
      Importantly, these proteins may comprise attractive therapeutic targets and novel
      disease markers for colon cancer. To perform a proteomics-based inventory of
      these so-called "anchorless" surface proteins, intact colon adenocarcinoma SW480
      cells were labeled with membrane-impermeable biotin after which only soluble
      biotinylated proteins were isolated and identified by nanoLC-MS/MS. Computer
      assisted analysis predicted that only 9 of the 97 identified surface-exposed
      proteins have predicted secretory signal peptides, whereas 2 other proteins have
      a putative transmembrane segment. Of the 9 proteins with putative signal
      peptides, 1 was predicted to be retained at the cell surface by a GPI-anchor,
      whereas 5 other proteins contained an ER-retention motif (KDEL) that should
      prevent them from being sorted to the cell surface. The remaining 86 soluble
      "surface" proteins lack known export signals and the possibility that these
      proteins are candidate substrates of non-classical transporters or exported by
      unconventional mechanisms is discussed. Alternatively, the large number of
      "intracellular" and ER-resident proteins may imply that biotinylation approaches
      are not only specific for surface proteins, but also biased against a certain
      subset of non-surface proteins. This underscores the importance of post-proteomic
      verification of proteomics-based inventories on surface-exposed proteins, which
      eventually should reveal to which extent non-classical export and retention
      mechanisms contribute to the sorting of "anchorless" proteins to the surface of
      colon tumor cells.

PMID- 17030025
TI  - A novel type of lysine oxidase: L-lysine-epsilon-oxidase.
AB  - The melanogenic marine bacterium M. mediterranea synthesizes marinocine, a
      protein with antibacterial activity. We cloned the gene coding for this protein
      and named it lodA [P. Lucas-Elio, P. Hernandez, A. Sanchez-Amat, F. Solano,
      Purification and partial characterization of marinocine, a new broad-spectrum
      antibacterial protein produced by Marinomonas mediterranea. Biochim. Biophys.
      Acta 1721 (2005) 193-203; P. Lucas-Elio, D. Gomez, F. Solano, A. Sanchez-Amat,
      The antimicrobial activity of marinocine, synthesized by M. mediterranea, is due
      to the hydrogen peroxide generated by its lysine oxidase activity. J. Bacteriol.
      188 (2006) 2493-2501]. Now, we show that this protein is a new type of lysine
      oxidase which catalyzes the oxidative deamination of free L-lysine into 6
      semialdehyde 2-aminoadipic acid, ammonia and hydrogen peroxide. This new enzyme
      is compared to other enzymes related to lysine transformation. Two different
      groups have been used for comparison. Enzymes in the first group lead to 2
      aminoadipic acid as a final product. The second one would be enzymes catalyzing
      the oxidative deamination of lysine releasing H2O2, namely lysine-alpha-oxidase
      (LalphaO) and lysyl oxidase (Lox). Kinetic properties, substrate specificity and
      inhibition pattern show clear differences with all above mentioned lysine-related
      enzymes. Thus, we propose to rename this enzyme lysine-epsilon-oxidase (lod for
      the gene) instead of marinocine. Lod shows high stereospecificity for free L
      lysine, it is inhibited by substrate analogues, such as cadaverine and 6
      aminocaproic acid, and also by beta-aminopropionitrile, suggesting the existence
      of a tyrosine-derived quinone cofactor at its active site.

PMID- 17030027
TI  - Effects of reserpine on the plus-maze discriminative avoidance task: dissociation
      between memory and motor impairments.
AB  - We investigated the effects of reserpine (0.1-0.5 mg/kg) on the performance of
      mice in the plus-maze discriminative avoidance task (DAVT), which simultaneously
      evaluates memory and motor activity. All doses induced memory impairment
      (increased aversive arm time) but only 0.5 mg/kg reserpine decreased locomotion
      (entries in enclosed arms). The results suggest that the DAVT evaluation in
      reserpine-treated mice can be a useful model for studying cognitive deficits
      accompanied by motor impairments.

PMID- 17030028
TI  - Functional imaging with laser speckle contrast analysis: vascular compartment
      analysis and correlation with laser Doppler flowmetry and somatosensory evoked
      potentials.
AB  - Laser Speckle Contrast Analysis (LASCA), a novel, high-resolution blood flow
      imaging method, was performed on rat somatosensory cortex during functional
      activation. In the same animals, cerebral blood flow (CBF) was measured with
      Laser Doppler Flowmetry. To obtain a quantitative estimate of the underlying
      neuronal activity, somatosensory evoked potentials were recorded simultaneously
      with an epidural EEG. Our results show that: 1. CBF changes measured by LASCA or
      LDF are nonlinearly dependent on the magnitude of electrical neural activity
      revealed by somatosensory evoked potentials. 2. The magnitude of relative CBF
      changes measured by LASCA and LDF shows a strong correlation. 3. LASCA imaging
      localizes the highest relative changes of CBF in microcirculatory areas, with a
      smaller contribution by larger vessels. This study demonstrates that LASCA is a
      reliable method that provides 2D-imaging of CBF changes that are comparable to
      LDF measurements. It further suggests that functional neuroimaging methods based
      on CBF enhance areas of microcirculation and thus might prove more accurate in
      localizing neural activity than oxygenation related methods like BOLD-fMRI.

PMID- 17030030
TI  - Cannabinoid CB1 receptor antagonism modulates plasma corticosterone in rodents.
AB  - Although the involvement of cannabinoids and the endogenous cannabinoid system in
      the regulation of the hypothalamo-pituitary-adrenal axis in rodents is well
      documented, the precise role played by the cannabinoid type one (CB(1)) receptor
      in this effect has not been fully elucidated. Consequently, we investigated the
      role of CB(1) receptor in modulating plasma corticosterone concentrations through
      use of the potent and selective CB(1) receptor antagonist SR141716A and CB(1)
      receptor knockout mice. Rats were administered SR141716A (0.1, 0.3, and 1 mg/kg,
      i.v.) and blood was sampled at 0, 15, 60, 90 and 120 min postinjection. SR141716A
      dose- and time-dependently increased plasma corticosterone levels and maximum
      effects were obtained with the 1 mg/kg dose 60 min postinjection. In mice,
      SR141716A (0.1, 0.3, 1, 3, and 10 mg/kg, i.p.) also induced a dose-dependent rise
      in corticosterone levels 60 min postinjection; this rise reached plateau levels
      with the 0.3-1 mg/kg doses. The stimulatory effect of SR141716A (1 mg/kg, i.p.)
      on plasma corticosterone 60 min postinjection was abolished in the CB(1) receptor
      knockout mice, which did not show any difference in basal corticosterone levels
      as compared to their wild-type controls. Finally, the stimulatory effects of
      SR141716A (10 mg/kg, i.p.) on plasma corticosterone 60 min postinjection were
      retained after subchronic dosing (5 days, once daily) in mice. The present
      results indicate that SR141716A increases plasma corticosterone in rats and mice
      possibly through blockade of CB(1) receptors, an effect that is retained after
      subchronic dosing in mice. These data provide support for the notion that changes
      in plasma corticosterone concentrations may be used in the laboratory and the
      clinic to assess the effects of CB(1) receptor antagonism.

PMID- 17030029
TI  - In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione),
      [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell
      lines.
AB  - The anti-cancer chemotherapeutic potential of 1,10-phenanthroline-5,6-dione
      (phendione), [Cu(phendione)(3)](ClO(4))(2).4H(2)O and [Ag(phendione)(2)]ClO(4)
      were determined using four human cells lines, i.e. two neoplastic (A-498 and Hep
      G2) and two non-neoplastic (CHANG and HK-2). All of the phendione derivatives
      induced a concentration-dependant decrease in the viability of the four cell
      lines, with [Cu(phendione)(3)](ClO(4))(2).4H(2)O displaying greatest activity. In
      comparative studies, IC(50) values obtained with the two neoplastic cell lines
      showed a cytotoxic response which was between 3 and 35 times greater than that
      observed for the metal-based anti-cancer agent, cisplatin. Furthermore, metal
      phendione complexes, rather than simple solvated metal ions, were responsible for
      the observed cytotoxicity. Despite the high level of potency associated with
      these compounds they did not display an apparent cyto-selective profile, as they
      reduced the viability of both neoplastic and non-neoplastic cells. However,
      selected mechanistic studies showed that phendione and its metal complexes
      inhibited DNA synthesis which did not appear to be mediated through
      intercalation. Ames testing highlighted that all three compounds and their phase
      I metabolites were non-mutagenic, unlike cisplatin. Taken together, these results
      suggest that phendione and its Cu(II) and Ag(I) complexes may be capable of
      acting as highly effective anti-cancer therapies, which with careful
      administration could provide very potent and effective alternatives to cisplatin.

PMID- 17030032
TI  - Measuring quality in trauma care.
AB  - For use in quality measurement, a quality indicator (QI) must satisfy a number of
      criteria: there needs to be an established link with outcome; the indicator needs
      to measure what is considered current accepted practice; the targeted population
      requires precise definition; an appropriate risk adjustment strategy must be
      employed; the indicator should be feasible for collection; and, the measure must
      apply to a sufficient number of people so as to provide a measure of system-wide
      quality. This article discusses the use of QIs in the care of trauma patients. A
      series of QIs were originally promulgated by the American College of Surgeons
      Committee on Trauma (ACSCOT) and have been investigated for their utility in
      measuring quality in trauma systems by a number of US based studies. While some
      have advocated the implementation of several specific indicators, others have
      recommended discontinued use of a range of proposed QIs. This review highlights
      the difficulties of meeting these ideal indicator requirements in trauma care and
      proposes that the development of alternative indicators may provide more useful
      measures of quality care.

PMID- 17030031
TI  - Antinociceptive action of (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid in
      mice.
AB  - The objective of this study was to investigate spinal and supraspinal
      antinociceptive effects of a new synthetic compound, (+/-)-cis-(6-ethyl
      tetrahydropyran-2-yl)-formic acid (tetrahydropyran derivative). Its activity was
      compared with those from morphine. In peripheral models of inflammation and
      hyperalgesia, tetrahydropyran derivative significantly reduced nociceptive effect
      induced by acetic acid or formalin in mice. Tetrahydropyran derivative developed
      antinociceptive effect on the tail-flick and hot-plate tests with a long-acting
      curve maintaining the effect for 4 h longer than morphine. The opioid receptor
      antagonist naloxone totally reverted tetrahydropyran derivative effects on both
      models. Morphine as well as tetrahydropyran derivative induced tolerance and
      sedation in mice. However, tetrahydropyran derivative-induced tolerance had its
      onset retarded and the sedative activity was lower when compared to that induced
      by morphine. These results indicate that this new substance develops an
      antinociceptive activity and may be used in the future as a substitute for
      traditional opioids.

PMID- 17030033
TI  - Eimeria tenella enolase and pyruvate kinase: a likely role in glycolysis and in
      others functions.
AB  - Two cDNA codings for glycolytic enzymes were cloned from a cDNA library
      constructed from the schizont stage of the avian parasite Eimeria tenella.
      Enolase and pyruvate kinase cDNA were fully sequenced and compared with sequences
      of enzymes from other organisms. Although these enzymes were already detected in
      the sporozoite stage, their expression was enhanced during the first schizogony
      in accordance with the anaerobic conditions of this part of the life cycle of the
      parasite. Under activating conditions, microscopic observations suggest that
      these glycolytic enzymes were relocalised inside sporozoites and moreover were in
      part secreted. The enzymes were also localised at the apex of the first
      generation of merozoites. Enolase was partly observed inside the nucleus of
      sporozoites and schizonts. Taken together, these results suggest that glycolytic
      enzymes not only have a function in glycolysis during anaerobic intracellular
      stages but may also participate in the invasion process and, for enolase, in the
      control of gene regulation.

PMID- 17030034
TI  - Pro-apoptotic low-density lipoprotein subfractions in type II diabetes.
AB  - OBJECTIVE: To test the hypothesis that differences in subfractions of circulating
      lipoproteins between diabetic and non-diabetic subjects exist and might
      contribute to the increased risk for atherosclerosis in type II diabetics.
      METHODS AND RESULTS: LDL isolated from diabetic (D) and control subjects (N) were
      separated by FPLC into five subfractions (L1-L5). The fractional distributions of
      N- and D-LDL were not different, but the most strongly retained subfractions of D
      LDL (D-L5) were markedly more pro-apoptotic to bovine aortic endothelial cells in
      vitro than were the other subfractions in D- or N-LDL. D-L5 induced time- and
      concentration-dependent apoptosis that was inhibited by z-VAD-fmk. The most
      electronegative D-LDL subfractions contained substantial amounts of apoproteins
      AI, E and CIII, higher concentrations of non-esterified fatty acids and LpPLA2,
      and lower trinitrobenzenesulfonic acid (TNBSA) reactivities. Electronegative
      subfractions of D-LDL exhibited longer lag times and lower net increases in
      absorbance at 234 nm with Cu-catalyzed oxidation in vitro. CONCLUSIONS: The
      toxicities of electronegative subfractions of LDL from diabetic subjects to
      endothelial cells in vitro may be pivotal to vascular complications of diabetes
      in vivo, but the specific molecular alterations responsible for the toxicities of
      these subfractions of diabetic LDL are not known.

PMID- 17030036
TI  - Visualising viscous fingering in chromatography columns: high viscosity solute
      plug.
AB  - The interface between two fluids that have different viscosities and are
      percolating through a porous bed is unstable. Sooner or later, a flow instability
      termed viscous fingering (VF) develops. This phenomenon is important in
      chromatography because the solute plug does not have the same viscosity as the
      mobile phase. Because the sample is often much more viscous than the mobile
      phase, it is the interface at the rear of the sample band that is usually
      unstable. This situation is frequent in many modes of chromatography, e.g., in
      preparative and in multidimensional chromatography, in size exclusion
      chromatography, in frontal analysis, and in other physicochemical measurements
      (e.g., determination of adsorption isotherms and of mass transfer parameters).
      When the solute plug is more viscous than the mobile phase, we observed that the
      solute band compressed. When the viscosity contrast increased up to 0.30 cP,
      fingers appeared to trail behind the solute plug. The development of fingers then
      became more substantial as the viscosity contrast increased. To avoid effects
      associated with VF, the mobile phase and the solute plug should have nearly the
      same viscosity.

PMID- 17030037
TI  - Factors influencing newborns' preference for faces with eye contact.
AB  - We investigated newborns' sensitivity to the direction of gaze of another's face
      by using a preferential looking technique. This study extends earlier work on a
      preference for faces with direct gaze in newborns. In Experiment 1, we replicate
      the basic finding of Farroni and colleagues that newborns prefer to look at faces
      with direct gaze. In Experiments 2 and 3, we establish that a preference for
      faces with direct gaze in newborns is present only within the context of an
      upright face and a straight head, suggesting that relatively primitive
      configuration-sensitive mechanisms may be operating. Overall, these results
      further the view that relatively simple perceptual biases in newborns may be an
      essential foundation for later social-cognitive development.

PMID- 17030035
TI  - Carotid artery plaque thickness is associated with increased serum calcium
      levels: the Northern Manhattan study.
AB  - BACKGROUND: Elevated serum calcium concentrations are associated with vascular
      calcification and cardiovascular disease. It is unknown whether there is a
      relationship between high-normal serum calcium levels and sub-clinical vascular
      effects. We investigated the association between serum calcium and carotid plaque
      thickness, a powerful early predictor of clinical coronary and cerebrovascular
      events. METHODS: Epidemiological study of 1194 subjects from the Northern
      Manhattan Study cohort, a prospective community-based study designed to
      investigate risk factors for vascular disease in different race-ethnic groups.
      RESULTS: Subjects with carotid plaque had higher corrected serum calcium levels
      within the normal range than those without carotid plaque (2.21+/-0.09 mmol/L
      versus 2.19+/-0.09 mmol/L, p<0.002). The relationship between carotid plaque and
      serum calcium persisted after adjustment for traditional cardiovascular risk
      factors. Subjects in the top quintile of maximal carotid plaque thickness
      (>or=1.7 mm) were more likely to be in the highest quintile of serum calcium
      level (OR=1.64, 95% CI=1.17-2.29, p<0.004). The interaction of age and corrected
      serum calcium was the most significant predictor of carotid plaque thickness when
      traditional vascular risk factors were considered (p<0.001). CONCLUSIONS: Serum
      calcium levels in a multi-ethnic population of older men and women were
      positively associated with carotid plaque thickness, a powerful early predictor
      of clinical coronary and cerebrovascular events.

PMID- 17030038
TI  - Time monitoring and executive functioning in children and adults.
AB  - This study examined time-based prospective memory performance in relation to
      individual and developmental differences in executive functioning. School-age
      children and young adults completed six experimental tasks that tapped three
      basic components of executive functioning: inhibition, updating, and mental
      shifting. Monitoring performance was examined in a time-based prospective memory
      task in which participants indicated the passing of time every 5min while
      watching a movie. Separate analyses of the executive functioning data yielded a
      two-factor solution for both age groups, with the updating and inhibition tasks
      constituting a common factor and the shifting tasks constituting a separate
      factor. Both children and adults showed accelerating monitoring functions with
      low rates of clock checking during the early phase of each 5-min interval.
      However, compared with adults, children needed more clock checks for obtaining
      the same level of response accuracy. Executive functioning had selective effects
      on time-based prospective memory performance. In both children and adults,
      monitoring performance was related to the inhibition and updating components, but
      not to the shifting component, of executive functioning. We conclude that
      difficulties in temporary maintenance and updating of working memory contents may
      create discontinuities in sense of time, leading to an increased reliance on
      external cues for time keeping.

PMID- 17030039
TI  - Connections, connections, connexins: towards systems biology paradigm of cardiac
      arrhythmia.

PMID- 17030040
TI  - A thiol labelling competition experiment as a probe for sidechain packing in the
      kinetic folding intermediate of N-PGK.
AB  - Protein folding is directed by the sequence of sidechains along the polypeptide
      backbone, but despite this the developement of sidechain interactions during
      folding is not well understood. Here, the thiol-active reagent, dithio
      nitrobenzoic acid (DTNB), is used to probe the exposure of the cysteine sidechain
      thiols in the kinetic folding intermediates of the N-terminal domain of
      phosphoglycerate kinase (N-PGK) and a number of conservative (I-, L-, or V-to-C)
      single cysteine variants. Rapid dilution of chemically denatured protein into
      folding conditions in the presence of DTNB allowed the degree of sidechain
      protection in any rapidly formed intermediate to be determined through the
      analysis of the kinetics of labelling. The protection factors derived for the
      intermediate(s) were generally small (<25), indicating only partial burial of the
      sidechains. The distribution of protection parallels the previously reported
      backbone amide protection for the folding intermediate of N-PGK. These
      observations are consistent with the hypothesis that such intermediates resemble
      molten globule states; i.e. with native-like backbone hydrogen bonding and
      overall tertiary structure, but with the sidechains that make up the hydrophobic
      protein core dynamic and intermittently solvent exposed. The success of the
      competition technique in characterizing this kinetic intermediate invites
      application to other model systems.

PMID- 17030041
TI  - Global analyses of evolutionary dynamics and exhaustive search for social norms
      that maintain cooperation by reputation.
AB  - Reputation formation is a key to understanding indirect reciprocity. In
      particular, the way to assign reputation to each individual, namely a norm that
      describes who is good and who is bad, greatly affects the possibility of
      sustained cooperation in the population. Previously, we have exhaustively studied
      reputation dynamics that are able to maintain a high level of cooperation at the
      ESS. However, this analysis examined the stability of monomorphic population and
      did not investigate polymorphic population where several strategies coexist.
      Here, we study the evolutionary dynamics of multiple behavioral strategies by
      replicator dynamics. We exhaustively study all 16 possible norms under which the
      reputation of a player in the next round is determined by the action of the self
      and the reputation of the opponent. For each norm, we explore evolutionary
      dynamics of three strategies: unconditional cooperators, unconditional defectors,
      and conditional cooperators. We find that only three norms, simple-standing,
      Kandori, and shunning, can make conditional cooperation evolutionarily stable,
      hence, realize sustained cooperation. The other 13 norms, including scoring,
      ultimately lead to the invasion by defectors. Also, we study the model in which
      private reputation errors exist to a small extent. In this case, we find the
      stable coexistence of unconditional and conditional cooperators under the three
      norms.

PMID- 17030042
TI  - Isometric contraction of microvascular pericytes from mouse brain parenchyma.
AB  - Pericytes were isolated and cultured from mouse cerebroparenchymal microvessels.
      A single pericyte clone was three-dimensionally cultured in a collagen gel by
      adding tensile stress, resulting in the reconstruction of narrow stringy fibers.
      When the contractility of these fibers was evaluated isometrically, they
      contracted in response to acetylcholine (ACh)1 or noradrenaline; this was
      accompanied by an increase in intracellular calcium concentration ([Ca(2+)]i).
      The fibers that were pre-contracted by ACh were completely relaxed by papaverine,
      which is a smooth-muscle relaxant. Moreover, the muscarinic ACh receptor
      antagonist atropine depressed the [Ca(2+)]i response that was induced by ACh.
      This study demonstrates for the first time the quantitative measurement of the
      contractions produced by cultured microvascular pericytes from mouse brain
      parenchyma.

PMID- 17030043
TI  - Change in shear stress (Deltatau)/hydraulic conductivity (Lp) relationship after
      pronase treatment of individual capillaries in situ.
AB  - A complex glycoprotein meshwork covers the inner wall of blood vessels and is
      implicated in mechanotransduction of fluid shear stress (tau). A relationship
      between Deltatau and capillary Lp has been established. The purpose of this study
      was to evaluate Lp in response to Deltatau after exposing the capillary lumen to
      a mild, non-specific protease selected to disrupt its inner matrix. We
      hypothesized that Lp would not correlate with Deltatau after enzyme treatment.
      Frogs (Rana pipiens, n=69) were pithed and the mesentery was exteriorized. Lp was
      assessed at 30 cm H2O using the modified Landis technique after an abrupt, square
      wave Deltatau produced by a physiologically relevant increase in pressure.
      Perfusate solutions were 10 mg ml-1 BSA/frog Ringer's (Control) or 0.1 mg ml-1
      pronase in BSA/Ringer's (1 min) then BSA/Ringer's alone (Test). Mean (+/-SE)
      control Lp following Deltatau was 2.2+/-0.2 x 10(-7) cm s-1 cm H2O-1 and
      individual values correlated positively with Deltatau (r=0.85, P<0.0001, n=41).
      After pronase, mean Test Lp (17.6+/-2.5 x 10(-7) cm s-1 cm H2O-1) was higher
      compared to control and Deltatau/Lp plots revealed two subsets of capillaries. Lp
      correlated strongly with Deltatau in capillaries with diameters<or=15 microm
      (r=0.91, P=0.0006, n=14) and also in a second subset of capillaries with
      diameters >15 microm (r=0.96, P=0.0001, n=8). Slopes were 3.9- and 8.7-fold
      higher, respectively, compared to control. These data suggest a protective role
      for luminal constituents of intact capillaries. Mechanisms involved in capillary
      responses to flow-induced, mechanical stimuli may be located in the cellular
      structures that form capillaries.

PMID- 17030044
TI  - Tonic adenosine A1 and A2A receptor activation is required for the excitatory
      action of VIP on synaptic transmission in the CA1 area of the hippocampus.
AB  - Adenosine can regulate synaptic transmission through modulation of the action of
      other neurotransmitters. The influence of adenosine on VIP enhancement of
      synaptic transmission in hippocampal slices was investigated. Facilitation of
      fEPSP slope by 1 nM VIP (23.3+/-1.3%) was turned into an inhibition (-12.1+/
      3.4%) when extracellular endogenous adenosine was removed using adenosine
      deaminase (ADA, 1U/ml). Blockade of adenosine A(1) receptors with 1,3-dipropyl-8
      cyclopentylxanthine (DPCPX, 10 nM) or of A(2A) receptors with ZM241385 (20 nM)
      attenuated the effect of VIP. When both DPCPX and ZM241385 were present the
      effect of VIP was abolished. In the presence of ADA, selective A(1) receptor
      activation with N(6)-cyclopentyladenosine (CPA, 15 nM) or A(2A) receptor
      activation with CGS21680 (10 nM) partially readmitted the excitatory effect of
      VIP on fEPSPs. In contrast, facilitation of PS amplitude by 1 nM VIP (19.1+/
      1.2%) was attenuated in the presence of ADA or DPCPX but was not changed by
      ZM241385. CPA, in the presence of ADA, fully restored the effect of VIP on PS
      amplitude. In conclusion, VIP facilitation of synaptic transmission to
      hippocampal pyramidal cell dendrites is dependent on both A(1) and A(2A) receptor
      activation by endogenous adenosine. VIP effects on PS amplitude are only
      dependent on A(1) adenosine receptor activation. This differential sensitivity to
      adenosine modulation might be due to the different VIP circuits contributing to
      VIP effects on pyramidal cell dendrites and pyramidal cell bodies.

PMID- 17030045
TI  - Primary reflex persistence in children with reading difficulties (dyslexia): a
      cross-sectional study.
AB  - The primary reflex system emerges during fetal life and is inhibited during the
      first year after birth. Our aim was to examine the effects of persistence of this
      early neurological system on the attainment of core literacy skills in dyslexic
      and non-dyslexic poor readers. We assessed the prevalence of a persistent primary
      reflex in a cross-sectional, representative sample of children (n=739) aged 7-9
      years old attending mainstream primary school in Northern Ireland using
      standardised educational tests, and a clinical diagnostic test for a primary
      reflex (the asymmetrical tonic neck reflex (ATNR)). Multiple regression analyses,
      involving all of the sample children, revealed that persistence of the ATNR was
      significantly predictive of attainments in reading (t=-8.34, p<.001), spelling
      (t=-8.00, p<.001), non-word reading (t=-16.15, p<.001), and verbal IQ (t=-4.71,
      p<.001). ANOVA tests revealed that there were no differences between the
      performance of dyslexic and non-dyslexic poor readers on any of the outcome
      measures (reading (F(1, 289)=0.51, p=.48), spelling (F(1, 289)=0.02, p=.90), non
      word reading (F(1, 289)=0.76, p=.38), ATNR level (F(1, 289)=2.54, p=.11)).
      Further ANOVA tests revealed that males had significantly higher levels of
      persistent reflex than females (F(1, 737)=15.21, p<.001), and that children from
      socially disadvantaged backgrounds had significantly higher levels of reflex than
      children who were not socially disadvantaged (F(1, 737)=20.84, p<.001). The
      findings suggest that for many children in mainstream schooling, the attainment
      of core educational skills may be affected by the persistence of a brainstem
      mediated reflex system that should have been inhibited in the first year after
      birth. Furthermore, these findings suggest that dyslexia is not a distinct
      category of poor reading, and that it may be more valid to term all poor readers
      as dyslexic irrespective of IQ.

PMID- 17030046
TI  - Verb generation in children and adolescents with acute cerebellar lesions.
AB  - The aim of the present study was to examine verb generation in a larger group of
      children and adolescents with acute focal lesions of the cerebellum. Nine
      children and adolescents with cerebellar tumours participated. Subjects were
      tested a few days after tumour surgery. For comparison, a subgroup was tested
      also 1 or 2 days before surgery. None of the children had received radiation or
      chemotherapy at or before the time of testing. Eleven age- and education-matched
      control subjects participated. Subjects had to generate verbs to blocked
      presentations of photographs of objects. As control condition, the objects had to
      be named. Furthermore, dysarthria was quantified by means of a sentence
      production and syllable repetition task. Detailed analysis of individual 3D-MR
      images revealed that lesions affected cerebellar hemispheres in all children and
      adolescents. The right cerebellar hemisphere was affected in four and the left
      hemisphere in five subjects. In the present study, naming and verb generation
      accuracy were preserved in the majority of subjects with cerebellar lesions. No
      significant signs of learning deficits were observed, as reduction of reaction
      times over blocks was not different compared to controls. There was a trend of
      children and adolescents with right-hemispheric lesions to perform worse compared
      to controls. In this group, however, significant signs of dysarthria were
      present. In sum, no significant signs of disordered verb generation were observed
      in children and adolescents with acute cerebellar lesions. Findings suggest that
      the role of the cerebellum in verb generation may be less pronounced than
      previously suggested. Findings need to be confirmed in a larger group of subjects
      with acute focal lesions.

PMID- 17030047
TI  - Is Broca's area involved in the processing of passive sentences? An event-related
      fMRI study.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate whether
      activation in Broca's area is greater during the processing of passive versus
      active sentences in the brains of healthy subjects. Twenty Japanese native
      speakers performed a visual sentence comprehension task in which they were asked
      to read a visually presented sentence and to identify the agent or the patient in
      the sentence by pressing a button. We found that the processing of passive
      sentences elicited no greater activation than that of active sentences in Broca's
      area. However, passive sentences elicited greater activation than active
      sentences in the left frontal operculum and the inferior parietal lobule. Thus,
      our neuroimaging results suggest that deficits in the comprehension of passive
      sentences in Japanese aphasics are induced not by lesions to Broca's area, but to
      the left frontal operculum and/or the inferior parietal lobule.

PMID- 17030049
TI  - Funding for prevention: A global perspective.

PMID- 17030048
TI  - Exploring the functional and anatomical bases of mirror-image and anatomical
      imitation: the role of the frontal lobes.
AB  - Humans are the most imitative species on earth, but how imitation is accomplished
      and which areas of the brain are directly involved in different kinds of
      imitation is still under debate. One view is that imitation entails representing
      observed behaviours as a set of hierarchically organised goals, which
      subsequently drive the construction of an action pattern [Bekkering, H.,
      Wohlschlager, A., & Gattis, M. (2000). Imitation of gestures in children is goal
      directed. The Quarterly Journal of Experimental Psychology, 53, 153-164;
      Wohlschlager, A., Gattis, M., & Bekkering, H. (2003). Action generation and
      action perception in imitation: An instance of the ideomotor principle.
      Philosophical Transactions of the Royal Society of London, 358, 501-515]. On this
      view, when working memory resources are limited, only the goals at the top-end of
      the hierarchy will be accurately reproduced. In the present study, neurologically
      intact participants and patients with frontal and non-frontal lesions were asked
      to make imitative responses that were either mirror-image (e.g., the observer's
      right side corresponding to the model's left side) or anatomically (e.g., the
      observer's right side corresponding to the model's right side) matching.
      Experiment 1 confirmed that individuals with brain damage, though globally
      impaired compared with neurologically intact controls, nevertheless followed the
      same goal hierarchy. However, there was a selective deficit in performing
      anatomical imitation for the frontal group. Experiment 2 demonstrated that the
      problem for frontal patients stemmed from an impaired ability to remember and
      reproduce incompatible stimulus-response mappings, which is fundamental for the
      selection of the appropriate frame of reference during anatomical imitation.

PMID- 17030050
TI  - Factors accounting for the rise in health-care spending in the United States: the
      role of rising disease prevalence and treatment intensity.
AB  - OBJECTIVES: To examine the factors responsible for the rise in health- care
      spending in the United States over the past 15 years. STUDY DESIGN AND METHODS:
      Nationally representative survey data from 1987 and 2003 were used to examine the
      top medical conditions accounting for the rise in spending. I also estimate how
      much of the rise is traced to rising treated disease prevalence and rising
      spending per case. RESULTS: The study finds most of the rise in spending is
      linked to rising rates of treated disease prevalence. The rise in prevalence is
      associated with the doubling of obesity in the US and changes in clinical
      thresholds for treating asymptomatic patients with certain cardiovascular risk
      factors. CONCLUSIONS: Most of the policy solutions offered in the US to slow the
      growth in spending do not address the fundamental factors accounting for spending
      growth. More aggressive efforts for slowing the growth in obesity among adults
      and children should be centre-stage in the efforts to slow the rise in health
      care spending.

PMID- 17030051
TI  - Regulation of estrogen receptor alpha by estradiol in pregnant and estradiol
      treated rats.
AB  - Estrogens play an important role in tissue metabolism through specific regulation
      of several intracellular pathways. We studied ERalpha regulation in muscle and
      adipose tissue from pregnant and estradiol treated rats. In both groups, we
      identified three different ERalpha inmunoreactive proteins (80, 67 and 46 kDa)
      using total protein extracts. Because it has been showed that estrogens are able
      to promote rapid effects in several cellular models, we looked for three ERalpha
      related proteins at plasma membrane. In skeletal muscle of both groups, we
      positively identified the three ERalpha-related isoforms in plasma membrane, but
      in adipose tissue from pregnant we were not able to identify ERalpha67, and in
      estradiol treated animals ERalpha80 was absent. Taking together, our results
      showed a tissue-specific regulation of whole-cell ERalpha-related proteins and
      ERalpha located at plasma membrane, which should be involved in non-genomic
      actions of 17beta-estradiol. The role of the three ERalpha inmunoreactive
      proteins is unknown, however, seems probably related to rapid activation of
      signalling pathways.

PMID- 17030052
TI  - HgeTx1, the first K+-channel specific toxin characterized from the venom of the
      scorpion Hadrurus gertschi Soleglad.
AB  - A novel toxin was identified, purified and characterized from the venom of the
      Mexican scorpion Hadrurus gertschi (abbreviated HgeTx1). It has a molecular mass
      of 3950 atomic mass units (a.m.u.) and contains 36 amino acids with four
      disulfide bridges established between Cys1-Cys5, Cys2-Cys6, Cys3-Cys7 and Cys4
      Cys8. It blocks reversibly the Shaker B K(+)-channels with a Kd of 52nM. HgeTx1
      shares 60%, 45% and 40% sequence identity, respectively, with Heterometrus
      spinnifer toxin1 (HsTX1), Scorpio maurus K(+)-toxin (maurotoxin) and Pandinus
      imperator toxin1 (Pi1), all four-disulfide bridged toxins. It is 57-58% identical
      with the other scorpion K(+)-channel toxins that contain only three disulfide
      bridges. Sequence comparison, chain length and number of disulfide bridges
      analysis classify HgeTx1 into subfamily 6 of the alpha-KTx scorpion toxins
      (systematic name: alpha-KTx 6.14).

PMID- 17030053
TI  - Twentieth century toxinology and antivenom development in Australia.
AB  - It was not until the last decade of the 19th century that an experimental
      approach (led by Bancroft in Queensland and Martin in Sydney and Melbourne)
      brought a higher plane of scientific objectivity to usher in the modern era of
      Australian toxinology. This Australia era, 1895-1905, coincided with and in some
      respects was the result of the new knowledge emerging from Europe and the
      Americas of the therapeutic effects of antitoxins. The subsequent systematic
      study of Australian venoms and toxins through to the 1930s and beyond, by
      Tidswell, Fairley, Ross, Kellaway and Cleland, set the foundation for Australia's
      leading reputation in venom research. As elsewhere, this development was to
      revolutionise the medical management of those victims who in the past had died in
      Australia from our venomous and toxic fauna. Morgan, Graydon, Weiner, Lane and
      Baxter at the Commonwealth Serum Laboratories emphasised the importance of
      cooperation between those expert at catching and milking the venomous creatures
      and those developing the antivenoms. Commercial antivenom manufacture began in
      Australia in 1930 with the tiger snake antivenom. This was followed by other
      antivenoms for the other important species (1955: taipan; 1956: brown snake;
      1958: death adder; 1959: Papuan black snake; 1961: sea snake; 1962: polyvalent)
      including the first marine antivenoms in the world (1956: stonefish antivenom;
      1970: box jellyfish) culminating, in 1980, with the release of the funnel web
      spider antivenom. More recent activity has focused on veterinary antivenoms and
      production of new generation human antivenoms for export (CroFab and ViperaTAB).
      This paper reviews some of the milestones of Australian toxinology, and antivenom
      development in particular, during the 20th century.

PMID- 17030054
TI  - Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of
      Turbina cordata in Northeastern Brazil.
AB  - A disease of the central nervous system in goats was observed in the
      municipalities of Juazeiro, Casa Nova and Curaca, state of Bahia, and Petrolina,
      state of Pernambuco, Northeastern Brazil. The disease was produced experimentally
      in two goats by the administration of dry Turbina cordata mixed with grain.
      Clinical signs were observed after the ingestion of 62 and 106 g/kg body weight
      in 28 and 54 days, respectively. The concentration of swainsonine in the plant
      varied from less than 0.001% to 0.14% (dry weight). Clinical signs of natural and
      experimental cases included difficulties in standing, ataxia, hypermetria, wide
      based stance, intention tremors, spastic paresis mainly in the hind legs,
      nystagmus, abnormal postural reactions, head tilting, and falling. Diffuse
      vacuolation of neurons, epithelial cells of pancreas, thyroids, and renal tubules
      were observed on the histology. From the electron microscopy of Purkinje cells
      the vacuoles represented dilated lysosomes. These findings demonstrated that T.
      cordata causes an acquired glycoprotein lysosomal storage disease. The
      intoxication occurs at least in an area of 27,000 km2 causing severe losses in
      goats, and some farmers report the disease also in cattle.

PMID- 17030055
TI  - Decrease in toxicity of microcystins LA and LR in drinking water by ozonation.
AB  - Unchlorinated treated waters from two Australian reservoirs were spiked with
      microcystin-LA and -LR extracted from a toxic scum of Microcystis aeruginosa. The
      two waters had considerably different water quality and therefore ozone demands.
      The spiked sample waters were ozonated using the batch method of ozonation at a
      range of doses and the samples were analysed for toxins using high-performance
      liquid chromatography (HPLC). The toxin content of the samples was also
      determined using a protein phosphatase type 2A inhibition assay (PP2A) and
      toxicity via the standard mouse bioassay. The HPLC results correlated well with
      the PP2A results and toxicity tests for both waters. A loss of both toxins and
      toxicity was observed with increasing ozone dose, resulting in a complete loss of
      toxicity for both waters once an ozone residual had been achieved. At this ozone
      residual no toxin was detected using HPLC. The results indicate that microcystins
      are not transformed into toxic by-products.

PMID- 17030056
TI  - The mammalian fauna associated with an archaic hominin skullcap and later
      Acheulean artifacts at Elandsfontein, Western Cape Province, South Africa.
AB  - The Elandsfontein site, Western Cape Province, South Africa, is well known for an
      archaic hominin skullcap associated with later Acheulean artifacts. The site has
      also provided nearly 13,000 mammalian bones that can be identified to skeletal
      part and taxon. The assemblage derives from 49 species, 15 of which have no
      historic descendants. Comparisons to radiometrically dated faunas in eastern
      Africa indicate an age between 1 million and 600 thousand years ago. Unique
      features of the fauna, including the late occurrence of a dirk-toothed cat and a
      sivathere, may reflect its geographic origin in a region that was notable
      historically for its distinctive climate and high degree of biotic endemism.
      Together, taxonomic composition, geomorphic setting, and pollen extracted from
      coprolites indicate the proximity of a large marsh or pond, maintained by a
      higher water table. The small average size of the black-backed jackals implies
      relatively mild temperatures. The sum of the evidence places bone accumulation
      during one of the mid-Pleistocene interglacials that were longer and cooler than
      later ones, including the Holocene. The geomorphic context of the fauna presents
      no evidence for catastrophe, and most deaths probably resulted from attritional
      factors that disproportionately killed the young and old. However, only the
      dental-age profile of long-horned buffalo supports this directly. Field
      collection methods biased skeletal-part representation, but originally, it
      probably resembled the pattern in the younger, marsh-edge Acheulean occurrence at
      Duinefontein 2, 45 km to the south. Excavation there exposed multiple vertebral
      spreads, which probably mark carcasses from which hominins or large carnivores
      removed the meatier elements. Bone damage at both sites suggests that, despite
      abundant artifacts, hominins were much less important than carnivores in the bone
      accumulation. Together with limited observations from other sites, Elandsfontein
      and Duinefontein provisionally suggest that Acheulean-age hominins obtained few
      large mammals, whether by hunting or scavenging.

PMID- 17030057
TI  - D-dimer level is associated with the extent of pulmonary embolism.
AB  - OBJECTIVES: Our aim was to study the association between the level of D-dimer and
      the severity of pulmonary embolism (PE) as determined by various biochemical and
      radiological prognostic markers in order to investigate the potential value of D
      dimer as a prognostic marker for the severity of PE. PATIENTS AND METHODS: PE was
      diagnosed in 100 consecutive out-patients by multi-detector computerized
      tomography. One patient was excluded and the final cohort consisted of 99
      patients. Pulmonary Artery Obstruction Index (PAOI) and Right Ventricular/Left
      Ventricular (RV/LV) ratio were assessed. RESULTS: The median value for D-dimer
      was 5.0 mg/L (inter-quartile range: 1.8, 12.2). There was a significant
      association between log D-dimer, and between log RV/LV (r=0.45), log PAOI
      (r=0.5), and PaO(2) (r=0.40). The multivariate analysis showed an increased
      association between log D-dimer and between log RV/LV ratio (r=0.54) and log PAOI
      (r=0.52) after adjusting for age, gender and for the duration of symptoms.
      Significant association was found between the level of D-dimer and the most
      proximal level of PE (p<0.0005). There was a significant dose-response
      relationship between the level D-dimer and between Troponin-T and the frequency
      of thrombolysis (p<0.0005). In the subgroup of patients with D-Dimer over the
      upper quartile (>12.2), 12 (67%) patients had elevated Troponin-T and 8 (32%)
      patients received thrombolysis, compared to 1 (5%) patient with elevated Troponin
      T and none treated with thrombolysis in the subgroup of patients with D
      dimer<lower quartile. CONCLUSIONS: We have shown that the level of D-dimer is
      related to the severity of PE assessed by various radiological, biochemical and
      clinical markers and might have a potential value as prognostic marker for the
      severity of PE.

PMID- 17030058
TI  - Deregulation of tissue homeostasis in endometria from patients with polycystic
      ovarian syndrome with and without endometrial hyperplasia.
AB  - OBJECTIVE: To study the proteins involved in endometrial homeostasis in PCOS
      women. METHODS: Protein expression of Ki67, Bcl-2, Bax, Pro-Caspase-3 and Caspase
      3 by immunohistochemistry and/or Western blot, and DNA fragmentation using in
      situ 3'-end labeling of apoptotic cells, was measured in 9 samples of normal
      endometrium (NE), 12 PCOS endometria without treatment (PCOSE), 7 endometria from
      PCOS women with endometrial hyperplasia (HPCOSE) and 9 endometria from patients
      with endometrial hyperplasia (HE). RESULTS: Cell proliferation was higher in
      epithelium from PCOSE (P<0.05), HPCOSE and HE vs NE. A higher Bcl-2/Bax relative
      ratio in PCOSE and HPCOSE was observed, in absence of active Caspase-3 and scarce
      DNA fragmentation in the four groups of endometria studied. CONCLUSION: As the
      apoptosis was scarce in all of the groups studied, endometrial homeostasis
      deregulation in PCOS could be a result of increased proliferation. Therefore, the
      onset of endometrial hyperplasia in PCOS endometrium could be linked to
      inadequate cell proliferation, and concomitantly to inadequate cell survival.

PMID- 17030059
TI  - Analysis of the antinociceptive effect of the proanthocyanidin-rich fraction
      obtained from Croton celtidifolius barks: evidence for a role of the dopaminergic
      system.
AB  - In a previous study, we demonstrated the antinociceptive effect of 63SF, a
      proanthocyanidin-rich fraction obtained from Croton celtidifolius barks, in
      chemical and thermal behavioural models of pain in mice. The current study now
      investigate the possible mechanisms underlying the antinociceptive activity of
      63SF in the formalin test, by using drugs which interfere with systems that are
      implicated in descending control of nociception. The antinociceptive effect of
      63SF (11 mg/kg, i.p., given 30 min prior to 2.5% formalin) was not altered by pre
      treatment of animals 45-50 min beforehand with either prazosin (alpha(1)
      adrenergic antagonist; 0.15 mg/kg, i.p.), yohimbine (alpha(2)-adrenergic
      antagonist; 0.15 mg/kg, i.p.), ketanserin (5-HT(2A)-receptor antagonist; 1.0
      mg/kg, i.p.), or l-arginine (substrate for NO synthase, 600 mg/kg, i.p.). On the
      other hand, treatment with sulpiride, an antagonist of dopaminergic D(2)
      receptors (1.0 mg/kg, i.p., 45 min of pre-treatment), reversed the
      antinociceptive activity of 63SF. Pre-treatment of animals with reserpine (5
      mg/kg, i.p., 24 h beforehand) did not alter the antinociceptive effect of 63SF.
      The current results support the view that the 63SF exerts antinociceptive effects
      by enhancing the activity of descending control, possibly by direct stimulation
      of dopaminergic D(2) receptors.

PMID- 17030060
TI  - Functional organization of TRPC-Ca2+ channels and regulation of calcium
      microdomains.
AB  - TRP family of proteins are components of unique cation channels that are
      activated in response to diverse stimuli ranging from growth factor and
      neurotransmitter stimulation of plasma membrane receptors to a variety of
      chemical and sensory signals. This review will focus on members of the TRPC sub
      family (TRPC1-TRPC7) which currently appear to be the strongest candidates for
      the enigmatic Ca(2+) influx channels that are activated in response to
      stimulation of plasma membrane receptors which result in phosphatidyl inositol
      (4,5)-bisphosphate (PIP(2)) hydrolysis, generation of IP(3) and DAG, and IP(3)
      induced Ca(2+) release from the intracellular Ca(2+) store via inositol
      trisphosphate receptor (IP(3)R). Homomeric or selective heteromeric interactions
      between TRPC monomers generate distinct channels that contribute to store
      operated as well as store-independent Ca(2+) entry mechanisms. The former is
      regulated by the emptying/refilling of internal Ca(2+) store(s) while the latter
      depends on PIP(2) hydrolysis (due to changes in PIP(2) per se or an increase in
      diacylglycerol, DAG). Although the exact physiological function of TRPC channels
      and how they are regulated has not yet been conclusively established, it is clear
      that a variety of cellular functions are controlled by Ca(2+) entry via these
      channels. Thus, it is critical to understand how cells coordinate the regulation
      of diverse TRPC channels to elicit specific physiological functions. It is now
      well established that segregation of TRPC channels mediated by interactions with
      signaling and scaffolding proteins, determines their localization and regulation
      in functionally distinct cellular domains. Furthermore, both protein and lipid
      components of intracellular and plasma membranes contribute to the organization
      of these microdomains. Such organization serves as a platform for the generation
      of spatially and temporally dictated [Ca(2+)](i) signals which are critical for
      precise control of downstream cellular functions.

PMID- 17030061
TI  - Neuromotor function in a cohort of Danish steel workers.
AB  - OBJECTIVE: With a longitudinal design to evaluate possible neuromotor impairment
      in a cohort of steel workers exposed to metal dust. MATERIAL: Ninety-two
      employees from a steel works were examined in 1989 and 1995. Sixty were re
      examined in 2003. A non-matched control group was examined in 1996 (n=19) and in
      2003 (n=14). Median blood manganese in 1989, 1995 and 2003 was 149, 171 and 155
      nmol/l. Median blood lead in 1989 and 2003 was 0.76 and 0.22 micromol/l. Median
      air concentration of manganese at the steel works was estimated to be 0.11 mg/m3
      in 1970s and was 0.03 mg/m3 in 1990s. Median air concentration of lead was
      estimated to be 0.13 mg/m3 in 1970s and was 0.01 mg/m3 in 1990s. METHOD: The
      Catsys 2000 system developed by Danish Product Development is computer-based
      device for measuring hand tremor, hand coordination and reaction time. RESULTS:
      Over all there were no statistically significant differences in neuromotor
      function between the participating steel workers, non-participating steel workers
      and controls in 1995/1996. Only reaction time for the right hand was slower for
      the participating steel workers. Compared with the control group the steel
      workers showed a decline in the ability to perform fast precise hand
      pronation/supination and finger tapping from 1995 to 2005. Correlation analysis
      showed no associations between test results for fast hand coordination and blood
      manganese and lead. Only seniority was associated with deterioration of beat
      regulation of fast pronation/supination of the hands. DISCUSSION: On a group
      basis the changes were subclinical, but they should none the less be taken
      seriously. CONCLUSION: Changes of neuromotor function measured as the ability to
      perform fast precise pronation/supination of the hands and fast precise finger
      tapping was shown in this cohort of steel workers. No causal relationships could
      be shown.

PMID- 17030062
TI  - Changes in spontaneous behaviour and altered response to nicotine in the adult
      rat, after neonatal exposure to the brominated flame retardant, decabrominated
      diphenyl ether (PBDE 209).
AB  - Polybrominated diphenyl ethers (PBDEs), which are used as flame retardants, have
      recently been shown to increase in the environment and in human milk, which is
      also true for the decabrominated congener, 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE
      209). We have recently reported that neonatal exposure to PBDE 209 can induce
      persistent aberrations in spontaneous behaviour, in mice, effects that get worse
      with age. Other PBDE congeners affect learning and memory functions and the
      cholinergic system in adult mice and rats. The present study indicates that
      spontaneous behaviour, along with the cholinergic system during its developing
      stage, can be targets for PBDE 209 in the rat. Neonatal oral exposure of male
      Sprague-Dawley rats, on postnatal day 3, to 6.7, and 20.1 mg PBDE 209/kg body
      weight, was shown to disrupt normal spontaneous behaviour at 2 months of age.
      Also, rats exposed to the high dose of PBDE 209 showed a different response to
      adult nicotine treatment, compared to control rats. These findings show
      similarities to observations made from neonatal exposure of rats or mice to
      2,2',4,4',5-pentaBDE (PBDE 99), 2,2',4,4',5,5'-hexaBDE (PBDE 153) and certain
      PCBs, compounds shown to affect both spontaneous behaviour and the cholinergic
      system. It is also clear from the present study and from recent studies from our
      research group that both lower and higher brominated diphenyl ethers can cause
      similar developmental neurotoxic effects in both mice and rats.

PMID- 17030063
TI  - Effects of chronic prednisone therapy on mood and memory.
AB  - BACKGROUND: In animals, stress and corticosteroids can be associated with both
      reversible and irreversible changes in the hippocampus. Changes in memory and
      hippocampal structure, perhaps in part due to cortisol elevations, are reported
      in some patients with mood disorders. Minimal data are available on the effects
      of long-term exposure to corticosteroids on the human hippocampus. We previously
      reported greater depressive symptom severity, poorer memory and smaller
      hippocampal volumes in patients with asthma or rheumatic diseases receiving long
      term prednisone therapy than in controls. METHODS: In this report, patients and
      controls were assessed a mean of 4 years after the first assessment to determine
      if depressive and manic symptoms and cognition remained stable, improved or
      worsened. Seven prednisone-treated patients and six controls were identified and
      agreed to reassessment with psychiatric symptom and neurocognitive measures.
      Follow-up MRIs for hippocampal volume analysis were available for two prednisone
      treated participants. RESULTS: With the exception of an increase in depressive
      symptoms in those receiving prednisone, participants and controls did not show
      significant change in mood or cognition from the initial assessment. One
      participant discontinued prednisone and showed improvement in psychiatric
      symptoms and cognition. Hippocampal volumes were available in two prednisone
      treated participants and showed inconsistent findings. LIMITATIONS: A limitation
      is the small sample size. CONCLUSIONS: Our findings, although preliminary in
      nature, suggest that long-term prednisone therapy is associated with initial
      changes in mood, memory and hippocampal volume that appear to stabilize over
      time.

PMID- 17030064
TI  - Negative cognitive style as a predictor of negative life events in depression
      prone individuals: a test of the stress generation hypothesis.
AB  - BACKGROUND: Stress generation effects in depressed individuals have been well
      documented. However, less is known about what personal attributes of depression
      prone individuals may contribute to the stress generation effect. This study
      investigated the role of negative cognitive style in predicting the occurrence of
      negative life events. METHODS: Undergraduates identified as either high (n=76) or
      low (n=81) in negative cognitive style were assessed for lifetime history of
      depression followed by periodic assessment over the course of six months for the
      occurrence of negative life events and depressive episodes. RESULTS: Individuals
      with negative cognitive styles generated more negative life events (dependent
      events and interpersonal events, but not more independent or achievement-related
      events) than individuals with more positive cognitive styles. These results
      appear to be unique to women. LIMITATIONS: Utilizing participants specifically
      chosen to be high or low in negative cognitive style may limit generalizability
      to other individuals. CONCLUSIONS: Results suggest that an underlying negative
      cognitive style may account for the stress generation effect often found in
      depressed individuals, particularly for women. Adequately addressing cognitive
      patterns in treatment or prevention programs may not only effectively reduce
      depression, but may also reduce the likelihood of experiencing negative life
      events that often serve as precipitants for depression.

PMID- 17030065
TI  - Analysis of human rotavirus G1P[8] strains by RFLP reveals higher genetic drift
      in the VP7 than the VP4 gene during a 4-year period in Mexico.
AB  - Several studies have demonstrated that rotaviruses of the G1P[8] genotype are
      among the most important worldwide. Sequence analysis of G1P[8] strains has
      revealed high genetic variability of VP4 and VP7 genes. The aim of this study was
      to investigate by restriction fragment length polymorphism (RFLP) analysis the
      genetic variability of the VP7 and VP4 genes within rotaviruses of the G1P[8]
      genotype. A total of 60 rotavirus-positive fecal samples genotyped as G1P[8],
      were collected from children with acute diarrhea under 5 years of age, between
      October 1995 and October 1998. The VP7 and VP4 genes were amplified by RT/PCR,
      using the Beg9/End9 primer pair and the Con3 and Con2 primers, respectively. VP7
      amplicons were digested with three restriction enzymes Hae III, Taq I and Rsa I
      in separate reactions and VP4 amplicons were digested similarly with
      endonucleases Hinf I, Sau96 I and Rsa I. Analysis of the digested VP7 and VP4
      amplicons showed a higher genetic drift for the VP7 gene (18 RFLPs) compared to
      the VP4 gene (9 RFLPs). The combination of profiles for both VP7 and VP4
      amplicons, showed 27 different patterns, none of them similar to the Wa-1 strain.
      Furthermore, RFLP analysis of these G1P[8] strains, clearly differentiated the
      viruses into two main clusters, both of them sharing the same restriction pattern
      for the VP4 gene, and a different one for the VP7 gene.

PMID- 17030066
TI  - Real-time RT-PCR detection of Bovine Viral Diarrhoea virus in whole blood using
      an external RNA reference.
AB  - A novel two-step real-time RT-PCR assay using SYBR Green I was developed for the
      detection of acute Bovine Viral Diarrhoea virus (BVDV) infection in whole blood
      from cattle. During infection animals experience a characteristic transient
      leucopenia and the number of cells per volume of blood changes over time; so
      quantitation of viral load by reference to a cellular housekeeping gene is not
      ideal as this may hide significant animal to animal variation. Therefore, to
      facilitate comparison of different samples, an external RNA reference was used
      for normalisation whereby each sample was spiked with the RNA virus, Canine
      Enteric Coronavirus (CECov), prior to RNA extraction, for comparative purposes.
      Real-time RT-PCR was carried out with two primer sets designed to amplify either
      a 156 bp region of the BVDV 5'-UTR or a 280 bp region of the CECov nucleocapsid
      protein gene. Linearity and efficiency of the assay was established and the
      method assessed using samples from BVDV-challenged calves. Viral RNA was
      quantified on days 6 and 14 post-challenge by real-time RT-PCR. Infectious virus
      isolation by traditional cell culture was negative after day 7. This study
      demonstrates encouraging results for rapid, sensitive and reliable detection of
      acute BVDV infection and provides an alternative real-time RT-PCR method for use
      on whole blood samples or samples where suitable housekeeping genes are not
      available.

PMID- 17030067
TI  - Semiquantitative one-step RT-PCR for simultaneous identification of human
      influenza and respiratory syncytial viruses.
AB  - A multiplex reverse transcription-polymerase chain reaction (mRT-PCR) method was
      developed for simultaneous detection and typing/subtyping of influenza viruses
      A/H1, A/H3 or B, and respiratory syncytial viruses A or B, followed by DNA
      semiquantitation using the Agilent 2100 Bioanalyzer. Such method provides a
      rapid, specific and sensitive diagnostic tool for detection and
      semiquantification of respiratory illness specimens.

PMID- 17030068
TI  - Development and validation of a real-time Taqman PCR assay for the detection and
      quantitation of infectious laryngotracheitis virus in poultry.
AB  - In this study, the development and validation of a real-time (ReTi) PCR assay is
      described using a Taqman labeled probe for the detection and quantitation of
      infectious larygotracheitis virus (ILTV) in chickens. The ReTi ILTV assay was
      highly specific with a quantitation limit of 100 viral template copies per
      amplification reaction. In experimentally infected, birds during early acute
      stages of infection, an average of 6.67 log(10) viral template
      copies/amplification reaction were detected, while at chronic late stages of
      infection an average of 2.86-3.27 log(10) viral template copies/amplification
      reaction were detected. A total of 246 tracheal swab samples collected from
      natural outbreaks of the disease were tested by virus isolation and the ReTi ILTV
      assay. Both assays agreed in 37% of the samples tested and the ReTi ILTV assay
      detected approximately 3.7 times more positives samples than virus isolation. A
      minimum of 5 log(10) viral template copies/amplification reaction were required
      from a tracheal swab to render a virus isolation positive result. In conclusion,
      the ReTi ILTV assay was highly specific, sensitive, reproducible, and capable of
      reliably quantifying viral nucleic acid directly from clinical samples.

PMID- 17030069
TI  - Plasma ghrelin levels after two high-carbohydrate meals producing different
      insulin responses in patients with metabolic syndrome.
AB  - Ghrelin is an orexigenic peptide produced in the stomach and its plasma levels
      are decreased acutely in response to ingested nutrients. To further clarify the
      role of insulin on ghrelin secretion, the present study was designed to
      investigate whether circulating ghrelin is affected differently by two mixtures
      of whole-grain breads known to produce low or high insulin responses in obese non
      diabetic subjects with metabolic syndrome. After an overnight fast eight obese
      subjects with the metabolic syndrome (3 men and 5 women; BMI 33.7+/-0.7 kg/m(2);
      age 55.6+/-1.8 y) received two different meals consisting of whole-grain rye or
      wheat breads. The comparison group (3 men and 5 women; BMI 22.5+/-0.5 kg/m(2);
      age 26.0+/-0.9 y) received a wheat bread meal. Blood samples were collected
      postprandially at time intervals for 2 h. Feelings of hunger and satiety were
      analyzed using the visual analogue scales. Ghrelin concentrations decreased after
      bread meals in lean individuals, but not in obese individuals with the metabolic
      syndrome. Despite the difference in plasma insulin response, there was no
      difference in plasma ghrelin or feelings of hunger and satiety in patients with
      metabolic syndrome. After both rye and wheat bread meals, the decrease in ghrelin
      concentrations seen in normal-weight individuals after wheat bread meal was
      absent in subjects with metabolic syndrome. Despite the different plasma insulin
      response in obese patients, ghrelin levels did not change in response to either
      type of bread meals. In addition, ghrelin levels did not correlate with insulin,
      glucose, HOMA1-IR and satiety and hunger ratings in either study groups. This
      indicates that regulation of ghrelin might be altered in obese patients with
      metabolic syndrome independently of insulin.

PMID- 17030070
TI  - Hyperhomocysteinemia due to cystathionine beta synthase deficiency induces
      dysregulation of genes involved in hepatic lipid homeostasis in mice.
AB  - BACKGROUND/AIMS: Cystathionine beta synthase (CBS) deficiency leads to severe
      hyperhomocysteinemia, which confers diverse clinical manifestations, notably
      fatty liver. Recently, abnormal lipid metabolism has been demonstrated in CBS
      deficient mice, a murine model of severe hyperhomocysteinemia. To gain further
      insights into effects of CBS deficiency on hepatic cholesterol metabolism, the
      expression of hepatic genes involved in biosynthesis, uptake and efflux was
      determined in CBS-deficient mice. METHODS: Gene expression analysis was performed
      on liver of CBS-deficient mice using quantitative real-time PCR. RESULTS: We
      found that CBS-deficiency in liver mice significantly increases expression of
      genes induced by endoplasmic reticulum stress and genes that regulate the
      expression of enzymes required for cholesterol and fatty acid biosynthesis and
      uptake, notably the scavenger receptor class B type I (SR-BI), concomitant with
      overexpression of SR-BI at the protein level. Moreover, we also found increased
      mRNA levels of ABCG5, ABCG8, ABCG1 and ABCA1, which play important roles in
      reverse cholesterol transport, associated with an upregulation of liver X
      receptors and a downregulation of the peroxisome proliferators-activated receptor
      alpha. CONCLUSIONS: We found that several ATP-binding cassette transporters and
      nuclear hormone receptors involved in liver lipid homeostasis are differentially
      expressed in liver of CBS-deficient mice.

PMID- 17030072
TI  - Leptin represses matrix metalloproteinase-1 gene expression in LX2 human hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: Collagen accumulation in liver fibrosis is due in part to
      decreased expression of matrix metalloproteinase (MMP)-1 relative to TIMP-1. LX-2
      hepatic stellate cells produce increased amounts of collagen and tissue inhibitor
      of metalloproteinase (TIMP)-1 in response to leptin. The effect of leptin on MMP
      1 production has not been reported. METHODS: LX-2 cells were treated with leptin
      with or without inhibitors. We determined: phosphorylation of Janus kinase (JAK)
      1 and -2, signal transducer and activator of transcription (STAT)3 and -5,
      extracellular signal-regulated kinase (ERK)1/2 and p38 by Western blot; H2O2
      concentration by a colorimetric method; MMP-1 mRNA levels and stability by
      Northern blot; MMP-1 promoter activity as well as pro-MMP-1 by ELISA; and active
      MMP-1 by fluorescence. RESULTS: LX-2 cells constitutively expressed the MMP-1
      gene and leptin repressed the basal level of MMP-1 mRNA and its promoter
      activity. The repression was mediated by JAK/STAT pathway in synergism with JAK
      mediated H2O2-dependent ERK1/2 and p38 pathways. ERK1/2 inhibited MMP-1 promoter
      activity, whereas p38 decreased the message stability, contributing to mRNA down
      regulation. Inhibition of MMP-1 gene diminished secreted pro-MMP-1 and active MMP
      1. CONCLUSIONS: Leptin represses MMP-1 gene expression via the synergistic
      actions of the JAK/STAT pathway and JAK-mediated H2O2-dependent ERK1/2 and p38
      pathways.

PMID- 17030071
TI  - Cholangiocarcinoma: modern advances in understanding a deadly old disease.
AB  - Cholangiocarcinomas are tumors that arise anywhere in the biliary tract,
      presumably of cholangiocyte origin. The global incidence of this rare disease is
      on the rise. Several known risk factors exist, and link chronic biliary
      inflammation to the pathogenesis of cholangiocarcinoma. Among these,
      amplification of the epidermal growth factor receptor, the interleukin-6
      signaling pathway, inducible nitric oxide, erb-2, and cyclooxygenase-2 are well
      defined. Most patients present late, with a median survival of months. Although,
      imaging studies and clinical context often indicate cholangiocarcinoma,
      pathologic and cytologic diagnosis is difficult to obtain. Advanced cytologic
      tests with fluorescence in situ hybridization or digital image analysis can
      increase diagnostic sensitivity. Surgical resection is the current therapy of
      choice for both intrahepatic and ductal cholangiocarcinomas. However, the 5-year
      survival is poor, with 60 to greater than 90% recurrence rates. In a single
      center experience, liver transplantation with neoadjuvant chemoirradiation, for
      highly selected patients, has a 5-year disease free survival of greater than 80%.
      Future targeted therapies will depend on a better understanding of the cellular
      and molecular biology of cholangiocarcinomas.

PMID- 17030074
TI  - Recombinant viral vectors: cancer vaccines.
AB  - To date cancer vaccines have yet to show efficacy in a phase III trial. However,
      the clinical benefit seen with monoclonal antibody mediated therapies (e.g.,
      Herceptin) has provided proof of principle that immune responses directed against
      tumour-associated antigens could have therapeutic potential. The failure of past
      cancer vaccine trials is likely due to several factors including the
      inappropriate choice of tumour antigen, use of an unoptimised antigen delivery
      system or vaccination schedule or selection of the wrong patient group. Any one
      of these variables could potentially result in the induction of an immune
      response of insufficient magnitude to deliver clinical benefit. Live recombinant
      viral vaccines have been used in the development of cancer immunotherapy
      approaches for the past 10 years. Though such vectors are self-adjuvanted and
      offer the ability to express multiple tumour-associated antigens (TAAs) along
      with an array of immune co-factors, arguably, they have yet to demonstrate
      convincing efficacy in pivotal clinical trials. However, in recent years, more
      coordinated studies have revealed mechanisms to optimise current vectors and have
      lead to the development of new advantageous vector systems. In this review, we
      highlight that live recombinant viral vectors provide a versatile and effective
      antigen delivery system and describe the optimal properties of an effective viral
      vector. Additionally, we discuss the advantages and disadvantages of the panel of
      recombinant viral systems currently available to cancer vaccinologists and how
      they can work in synergy in heterologous prime boost protocols and with other
      treatment modalities.

PMID- 17030073
TI  - A critical role of CpG motifs in a murine peritonitis model by their binding to
      highly expressed toll-like receptor-9 on liver NKT cells.
AB  - BACKGROUND: Toll-like receptor (TLR)-9 plays a critical role in the recognition
      of the CpG motifs, which is frequently observed in bacterial DNA. To date, there
      have not been any reports regarding the role of bacterial DNA in the systemic
      circulation on the development of sepsis. METHODS: We examined the expression of
      TLR-9 in the liver and spleen in a murine peritonitis model (CLP mice). We also
      measured the cytokine response of mononuclear cells (MNCs) from normal and CLP
      mice to CpG oligodeoxynucleotides (ODN) in vitro and in vivo. RESULTS: TLR-9
      expression on F4/80(+) and NK1.1(+)CD3epsilon(+) cells in the liver of CLP mice
      was elevated compared to sham-operated mice. With regard to cytokine production,
      we found that CpG ODN markedly stimulated the production of inflammatory
      cytokines by murine macrophages and liver MNCs. The intravenous injection of CpG
      ODN in mice that underwent CLP 12h earlier led to their increased cytokine
      production and their increased mortality. In addition, the depletion of NK/NKT
      cells contributed to improve their survival rate. CONCLUSIONS: Our results
      suggest that, in patients with overwhelming bacterial infection, bacterial DNA
      may induce liver toxicity that is mediated by liver NKT cells and macrophages
      that express high levels of TLR-9.

PMID- 17030075
TI  - Gemcitabine plus oxaliplatin combination (GEMOX regimen) in pretreated patients
      with advanced non-small cell lung cancer (NSCLC): a multicenter phase II study.
AB  - PURPOSE: To evaluate the activity and tolerance of gemcitabine in combination
      with oxaliplatin (GEMOX regimen) in pretreated patients with advanced non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-two patients with advanced
      NSCLC who had disease progression after a cisplatin- and taxane-based front-line
      regimen were treated with gemcitabine (1500 mg/m(2) on days 1 and 8) and
      oxaliplatin (130 mg/m(2) on day 8) every 3 weeks. The patients' median age was 62
      years and the performance status (WHO) was 0 for 11, 1 for 17 and 2 for 4
      patients. The treatment was second line for 22 (69%) and >or=third line for 10
      (31%) patients. RESULTS: Partial response was achieved in 5 (16%) patients,
      stable disease in 8 (25%) and progressive disease in 19 (59%). Two patients with
      stable disease and one patient with progressive disease while on previous
      chemotherapy experienced a partial response with GEMOX regimen. The median
      duration of response was 2.5 months (range, 1-11.5), the median time to tumor
      progression 3 months (range, 1-18) and the median survival 5.6 months (range, 1
      31). Grade III neutropenia occurred in five (16%) patients, grade III
      thrombocytopenia in two (6%) and grade III anemia in three (9%); moreover, grades
      II-III asthenia was reported in eight (25%) patients and grades II-III
      neurotoxicity in three (9%). CONCLUSION: The GEMOX combination is a relatively
      active and well tolerated second-line regimen in NSCLC patients pretreated with a
      taxane- and/or platinum-based chemotherapy.

PMID- 17030076
TI  - A peptide inhibitor of MurA UDP-N-acetylglucosamine enolpyruvyl transferase: the
      first committed step in peptidoglycan biosynthesis.
AB  - The MurA enzyme from Pseudomonas aeruginosa was purified to homogeneity and found
      to be biologically active as a UDP-N-acetylglucosamine (UNAG) enolpyruvyl
      transferase in a coupled enzyme assay where ATPase activity was measured by the
      release of inorganic phosphate. A microtiter plate assay coupled to competitive
      biopanning using the UDP-N-acetylglucosamine was used to screen 10(9) C-7-C and
      12-mers peptides from phage display libraries. From 60 phage-encoded peptides
      identified after the fourth round of biopanning, deduced amino acid sequences
      were aligned and two peptides were synthesized and tested for inhibition of the
      MurA-catalyzed reaction. The PEP 1354 peptide inhibited the ATPase activity of
      MurA with an IC(50) value of 200muM and was found to be a competitive inhibitor
      of UNAG. The pre-incubation of MurA with inhibitor indicated a time-independent
      inhibition. This time-dependent inhibition is the first report of peptide
      inhibitors of MurA, which represent the scaffold for the synthesis of inhibitory
      peptidomimetic molecules.

PMID- 17030077
TI  - The impact of active/cooperative instruction on beginning nursing student
      learning strategy preference.
AB  - Rapid changes in the nursing field and high demand for practicing nurses put
      pressure on nursing faculty to educate increasing numbers of nursing students,
      often without corresponding increases in resources. Although the use of active
      and cooperative instruction methods in the classroom has been associated with
      improved student learning, these practices require increased effort on the part
      of both faculty and students. In addition, little is known about whether these
      methods influence student nurses' use of these more elaborative processing
      strategies in their independent study. The purpose of this quasi-experimental
      investigation was to identify the impact of incorporating active and cooperative
      classroom instructional activities on student preference for teaching methods and
      use of learning strategies in independent study. A convenience sample of
      beginning baccalaureate nursing students at a large Mid-Atlantic University was
      randomly assigned by the registrar to two class sections. Students in one section
      received primarily active/cooperative instruction, while the other received
      primarily traditional lecture-based instruction. Results indicated that student
      nurses exposed to active/cooperative instructional methods had an increased
      preference for these methods after a semester of instruction, while those exposed
      to traditional instruction had a higher preference for traditional methods. In
      addition, students participating in active class instruction reported increased
      preference for more elaborative independent study strategies, although overall
      preference for both groups indicated a reliance on surface study strategies of
      memorization and recall. Implications for use of instruction and student testing
      methodologies are presented.

PMID- 17030078
TI  - Cross-protective immunity in mice induced by live-attenuated or inactivated
      vaccines against highly pathogenic influenza A (H5N1) viruses.
AB  - Because of the time required to identify and produce an antigenically well
      matched pandemic vaccine, vaccines that offer broader cross-reactive immunity and
      protection are desirable. We have compared a live attenuated influenza vaccine
      (LAIV) and inactivated influenza vaccine (IIV) based on a related H5
      hemagglutinin (HA) from a nonpathogenic avian influenza virus,
      A/Duck/Pottsdam/1042-6/86 (H5N2), for the ability to induce cross-reactive
      immunity and/or cross-protective efficacy against a contemporary highly
      pathogenic H5N1 viruses. Both LAIV and IIV provided cross-protection from
      systemic infection, severe disease, and death following lethal challenges with
      antigenically distinct A/Vietnam/1203/2004 (VN/1203) virus. Substantial levels of
      serum anti-VN/1203 HA IgG were detected in mice that received either IIV or LAIV,
      while nasal wash anti-VN/1203 HA IgA was detected in mice that received LAIV.
      Formulation of IIV with alum adjuvant augmented neutralizing antibody responses
      and protective efficacy. These results demonstrated that vaccination of mice with
      H5 IIV or LAIV induced a high degree of cross-protection from illness and death
      following lethal challenges with a heterologous H5N1 virus.

PMID- 17030079
TI  - Changing epidemiology of invasive pneumococcal disease in central Australia prior
      to conjugate vaccine: a 16-year study.
AB  - This study reports a 16-year prospective surveillance of invasive disease
      isolates in central Australian Aborigines. There were 621 (89.6% of total)
      isolates recovered from Aborigines. The mortality in children less than 5 years
      of age was 4% but rose to 34.5% in those over 49 years of age. The study
      documented continuing high rates of disease overall, but with significant
      reductions in incidence rates for children. In children under 2 years of age, the
      incidence fell by 32% from 2053 per 100,000 in the period 1985-1990 to 1184 per
      100,000 in the period 1996-2000. Rates of disease in adults showed no reduction
      despite an adult immunisation programme with 23 valent vaccine which occurred in
      the 1990s. Epidemics of serotypes 1, 5 and 12F were documented during the study
      period.

PMID- 17030080
TI  - What difference might sewage treatment performance make to endocrine disruption
      in rivers?
AB  - An assessment of the steroid estrogen removing performance of 23 different sewage
      treatment plants (STPs) was performed. The assessment relied on a model to
      estimate influent concentrations, and completed questionnaires on the STP
      treatment details from the relevant water companies. This information was
      compared with observed effluent 17beta-estradiol (E2) and estrone (E1)
      concentrations. The 10 biological filter plants (BFP) in the study performed
      poorly with only 30% (SD 31) removal on average for E1. This reduced E1 removal
      performance of the BFPs compared to all the other STP types in the survey was
      statistically significant (p<0.001). Scenarios of all the STPs as activated
      sludge types, and one as all BFP types were modelled using the GREAT-ER model set
      up for the Aire/Calder catchment in the UK. This difference was shown to have an
      important effect on predicted river E1 concentrations and consequent risk
      classifications.

PMID- 17030081
TI  - [Surgical management of cutaneous malignant melanoma. Review].
AB  - Nowadays managing a cutaneous malignant melanoma can concern different kind of
      physicians: dermatologists, general or plastic surgeons The primary surgical
      procedure is a major step of the treatment. Biopsy must be total to properly
      determine the thickness of the tumor in case of malignancy. Wide local excision
      of the scar is often necessary to decrease the local and general recurrence
      rates. Wide local excision must be performed conforming to its own surgical
      rules. Managing tumor located on the face or limb extremities is a matter of
      plastic surgery. Sentinel node biopsy has succeeded to elective lymph node
      dissection. This procedure allows research of lymphatic spreading of the disease.
      Practice of sentinel node biopsy must be achieved in a protocolar way. Topography
      of the lesion can modified achievement and results of this procedure. Prognosis
      benefit of sentinel biopsy is now clear. Elective lymph node dissection is only
      performed in case of invaded sentinel node or clinically invaded lymph nodes.
      Local or locoregional recurrences mainly respond to surgical treatment using wide
      excision. However, alternative solutions are being evaluated (isolated limb
      perfusion).

PMID- 17030082
TI  - Noradrenergic pain modulation.
AB  - Norepinephrine is involved in intrinsic control of pain. Main sources of
      norepinephrine are sympathetic nerves peripherally and noradrenergic brainstem
      nuclei A1-A7 centrally. Peripheral norepinephrine has little influence on pain in
      healthy tissues, whereas in injured tissues it has variable effects, including
      aggravation of pain. Its peripheral pronociceptive effect has been associated
      with injury-induced expression of novel noradrenergic receptors, sprouting of
      sympathetic nerve fibers, and pronociceptive changes in the ionic channel
      properties of primary afferent nociceptors, while an interaction with the immune
      system may contribute in part to peripheral antinociception induced by
      norepinephrine. In the spinal cord, norepinephrine released from descending
      pathways suppresses pain by inhibitory action on alpha-2A-adrenoceptors on
      central terminals of primary afferent nociceptors (presynaptic inhibition), by
      direct alpha-2-adrenergic action on pain-relay neurons (postsynaptic inhibition),
      and by alpha-1-adrenoceptor-mediated activation of inhibitory interneurons.
      Additionally, alpha-2C-adrenoceptors on axon terminals of excitatory interneurons
      of the spinal dorsal horn possibly contribute to spinal control of pain. At
      supraspinal levels, the pain modulatory effect by norepinephrine and
      noradrenergic receptors has varied depending on many factors such as the
      supraspinal site, the type of the adrenoceptor, the duration of the pain and
      pathophysiological condition. While in baseline conditions the noradrenergic
      system may have little effect, sustained pain induces noradrenergic feedback
      inhibition of pain. Noradrenergic systems may also contribute to top-down control
      of pain, such as induced by a change in the behavioral state. Following injury or
      inflammation, the central as well as peripheral noradrenergic system is subject
      to various plastic changes that influence its antinociceptive efficacy.

PMID- 17030083
TI  - Serological and virological profile of chronic HBV infected women at reproductive
      age in Greece. A two-year single center study.
AB  - OBJECTIVE: Seroprevalence of HBsAg in 26,746 women at reproductive age in Greece
      and evaluation of HBeAg/anti-HBe serological status as well as serum HBV-DNA
      levels in a subgroup of HBsAg(+) women at labor. STUDY DESIGN: Serological
      markers were detected using enzyme immunoassays. Serum HBV-DNA was calculated
      using a sensitive quantitative PCR assay, with a lower limit of quantification of
      200 copies/ml. RESULTS: Overall, 1.53% of women were HBsAg(+) and the majority of
      them (64.96%) were Albanian. Among Albanian women the mean prevalence of HBsAg
      was 4.9%, 5.57% among Asian women, and 1.29% among women from Eastern European
      countries. The prevalence of HBsAg among African (0.29%) and Greek women (0.57%)
      was very low and significantly lower in comparison with the mean value of the
      studied population. Only 2.67% of HBsAg(+) women were HBeAg(+). Of a subgroup of
      women in labor with available serum samples 28.6% had undetectable levels of
      viremia (<200 copies/ml) and 15.9% had extremely low levels of viral replication
      (<400 copies/ml). Only 12.7% of pregnant women evaluated at labor exhibited
      extremely high serum HBV-DNA levels (>10,000,000 copies/ml) whereas 42.8% of them
      exhibited HBV-DNA levels between 1500 and 40,000 copies/ml. CONCLUSIONS: The
      overall prevalence of HBsAg is relatively low among women at reproductive age in
      Greece but is higher among specific ethnic populations (Asian, Albanian). The
      HBeAg(-)/antiHBe(+) serological status is a finding observed in the vast majority
      of HBsAg(+) women of our study population, and a significant percentage of them
      (approximately 44.5%) exhibit extremely low or even undetectable levels of viral
      replication at labor, suggesting possibly that only a proportion of HBsAg(+)
      women in Greece exhibit an extremely high risk of vertical transmission of the
      infection.

PMID- 17030084
TI  - Information about a form (on the dynamic laws of morphogenesis).
AB  - How a developing embryo becomes "informed" about its form?" This problem remains
      obscure and controversial. We argue that the "information about a form" is
      distributed throughout three main components: the dynamic laws, the parameters
      and the initial/boundary conditions. In the absence of a dynamic law two other
      components are "blind", that is, do not contain any unambiguous information. We
      present a version of a dynamic law of morphogenesis, based upon the presumption
      of a feedback between passive and active mechanical stresses. We explore several
      models of shape formation based upon this law and show that, as depending upon
      the parameters values, they generate a large set of realistic shapes. Genetic and
      epigenetic basis of the models parameters is discussed.

PMID- 17030085
TI  - Temporal sub units in dendritic trees.
AB  - This simulation study examines the possibility that dendritic sub units can be
      defined according to temporal aspects in the timing of populations of synaptic
      inputs. A two cell model with passive dendritic trees is used, which is subject
      to both common and independent synaptic inputs, the presence of common synaptic
      input results in a tendency for correlated firing in the two cell model. The
      strength of this correlation is used to measure the efficacy of the common
      synaptic inputs in modulating the output discharge of each neurone. Our results
      suggest that a small fraction of the total synaptic input can effectively
      modulate the timing of output spikes, this phenomenon is not dependent on the
      physical location of the inputs on the dendritic tree. This phenomenon depends on
      the presence of temporal correlation between the pre-synaptic spike trains that
      provide the common input. We propose to refer to these as temporal sub units.

PMID- 17030086
TI  - Unidirectional movement of an actin filament taking advantage of temperature
      gradients.
AB  - An actin filament with heat acceptors attached to its Cys374 residue in each
      actin monomer could move unidirectionally even under heat pulsation alone, while
      in the total absence of both ATP and myosin. The prime driver for the movement
      was temperature gradients operating between locally heated portions on an actin
      filament and its cooler surroundings. In this report, we investigated how the
      mitigation of the temperature gradients induces a unidirectional movement of an
      actin filament. We then observed the transversal fluctuations of the filament in
      response to heat pulsation and their transition into longitudinally
      unidirectional movement. The transition was significantly accelerated when Cys374
      and Lys336 were simultaneously excited within an actin monomer. These results
      suggest that the mitigation of the temperature gradients within each actin
      monomer first went through the energy transformation to transversal fluctuations
      of the filament, and then followed by the transformation further down to
      longitudinal movements of the filament. The faster mitigation of temperature
      gradients within actin monomer helps build up the transition from the transversal
      to longitudinal movements of the filament by coordinating the interaction between
      the neighboring monomers.

PMID- 17030087
TI  - LH receptor gene mutations and polymorphisms: an overview.

PMID- 17030088
TI  - APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling
      complex.
AB  - A number of signaling proteins have been demonstrated to interact with follicle
      stimulating hormone (FSH) receptor (FSHR), including APPL1, 14-3-3tau and Akt2.
      To further define the repertoire of proteins involved in FSH-induced signal
      transduction, several signaling and adapter proteins were examined for the
      ability to associate with FSHR. This report shows that, in addition to APPL1,
      FSHR interacts with FOXO1a and APPL2. Moreover, APPL1 and APPL2 associate with
      one another via the N-terminus of APPL1, presumably via the Bin-Amphiphysin-Rvs
      (BAR) domain. The interactions between FSHR and APPL2 and between FSHR and FOXO1a
      evidently are distinct since FOXO1a does not associate with either APPL1 or with
      APPL2. Though APPL1 and APPL2 show some similarity in primary sequence, APPL1
      associates with Akt2, whereas APPL2 does not. This is the first documented
      difference in function between APPL1 and APPL2. These results suggest that FSHR,
      APPL1, APPL2, Akt2 and FOXO1a are organized into distinct scaffolding networks in
      the cell. Accordingly, the spatial organization of signaling and adapter proteins
      with FSHR likely facilitates and finely regulates the signal transduction induced
      by FSH.

PMID- 17030089
TI  - Targeting novel and established therapies for non-small cell lung cancer.
AB  - The prognosis in advanced non-small cell cancer (NSCLC) remains poor despite the
      introduction of several new cytotoxic drugs in the past decade. New approaches
      are required, and an improved understanding of lung cancer biology is identifying
      molecular mechanisms that are potential targets for novel therapies. Antagonists
      of signalling via the erbB and VEGFR families of transmembrane receptors have
      promising activity in NSCLC, and survival benefit has already been demonstrated
      for both erlotinib and bevacizumab. Although some patients enjoy dramatic and
      sustained responses to some of the new targeted drugs, overall response rates in
      unselected NSCLC patient groups are modest. This reflects the molecular
      heterogeneity of the disease; further clinical progress will require improved
      patient selection for treatment with both novel agents and established
      chemotherapy drugs. Here, we review recent advances in NSCLC biology likely to
      provide insight into such selection strategies.

PMID- 17030090
TI  - Pressurized liquid extraction with water as a tool for chemical and toxicological
      screening of soil samples at army live-fire training ranges.
AB  - Significant discrepancies in the results of risk assessments based on chemical
      and toxicity analyses of soils may arise through differences in the efficiency of
      the extraction or leaching methods used. A rapid technique that may be used in
      the screening phase of live-fire training ranges and suitable for extracting
      explosive residues is pressurized liquid extraction (PLE) with water. Therefore,
      PLE and the commonly used batch leaching method EN-124 57-2 were compared for
      their utility to extract specific residues from soil samples collected from the
      Canadian Forces Base (CFB) Petawawa, Ontario. After extraction the cytotoxicity
      of the samples were assessed in the L-929 growth inhibition assay. The PLE method
      yielded extracts suitable for direct use in the toxicity assay within 20 min as
      compared to 24h for the batch leaching method. Analysis of the extracts showed
      that the PLE water extracts tended to give higher recoveries of explosive
      residues and the resulting exposure concentrations were confirmed by higher
      cytotoxicities. Furthermore, gas chromatography-mass spectrometry analyses showed
      that the samples contained significant amounts of several munition-related
      stabilizers and plasticizers of toxicological significance in addition to the
      analysed explosive residues. In conclusion, PLE using water is a promising
      extraction technique for both chemical and toxicological screening of soil
      samples from areas that may be contaminated with explosive residues.

PMID- 17030091
TI  - Influence of chloride concentration on the formation of AOX in UV oxidative
      system.
AB  - In this study, the effects of chloride ion concentration and pH on UV oxidation
      treatment were examined. Acetone and sodium dodecyl sulfate (ABS) were used as
      organic substances. The treatment efficiencies of these chemicals by UV/H(2)O(2)
      oxidation using a laboratory scale UV-free surface reactor (UV-FSR) with or
      without Cl(-) addition at different pH values was compared. Results of this study
      indicated that Cl(-) concentration and the chemical structure of the substances
      are more decisive than pH in the oxidation process. There was no AOX at the start
      of the experiments but as a result of oxidation a de novo synthesis of AOX was
      observed, and these AOX(de novo) compounds were destroyed during the treatment.
      Treatment was followed by TOC and AOX measurements. Approximately 98% and 95% TOC
      removal efficiencies were obtained for the treatment of acetone and ABS
      containing wastewaters, respectively.

PMID- 17030092
TI  - Degradation characteristics of waste lubricants under different nutrient
      conditions.
AB  - We investigated the limits and extent of lubricants biodegradation at different
      nutrient conditions and evaluated several soil biological activities with regard
      to their usefulness for monitoring the bioremediation process in a soil
      contaminated with lubricants. To examine the effects of nutrient addition on
      lubricants biodegradation, a bench-scale investigation was conducted under
      different nutrient conditions for over 105 days testing period. When nutrients
      were added to contaminated soil with aged lubricant, great stimulation was
      occurred in fertilized soil for hydrocarbon degradation activity compared to non
      fertilized soil. At the end of the experiment (105 days after), the initial level
      of contamination (9320+/-343 mg/kg) was reduced by 42-51% in the fertilized soil,
      whereas, only 18% of the hydrocarbon was eliminated in the non-fertilized soil.
      The effect of biostimulation of indigenous soil microorganisms declined with
      time, apparently 42% of the initial concentration of hydrocarbon remained at the
      end of experiment. Lubricants biodegradation process could be monitored well by
      soil biological parameters. In fertilized soil, biological parameters (number of
      HUB, soil respiration, dehydrogenase and catalase activities) were significantly
      enhanced and correlated with each other, as well as the residual lubricant
      concentration.

PMID- 17030093
TI  - Sensorimotor adaptation to inertial forces in a multi-force environment does not
      depend on the number of targets: indirect validation of the altered
      proprioception hypothesis.
AB  - The ability of our sensorimotor system to adapt to changing and complex
      environmental demands has been under experimental scrutiny for more than a
      century. Previous works have shown that aimed arm movements adapt quickly and
      completely to Coriolis force, but incompletely to the combination of Coriolis and
      centrifugal forces without visual cues. Two hypotheses may be advanced to explain
      this discrepancy: the workspace-exploration hypothesis, and the degraded
      proprioception hypothesis. The aim of this study was to distinguish between the
      above two alternatives by comparing adaptive improvement during off-axis rotation
      in subjects pointing at one, three or seven different targets in complete
      darkness. Two main results emerge: (a) off-axis rotation led initially to errors
      in the direction of Coriolis force and in the opposite direction of the
      centrifugal force; (b) the size of the visited workspace has no effect on the way
      the subjects adapt to a multi-force environment. The lack of a target-number
      effect and the persistence of lateral errors in the pointing movements performed
      during rotation of the platform, support the degraded-proprioception rather than
      the workspace-exploration hypothesis of adaptation to a multi-force environment.

PMID- 17030094
TI  - Shared cognitive processes underlying performance on the Wisconsin Card Sorting
      Test and the Stroop Test in patients with schizophrenia: a measurement artifact?
AB  - We explored the hypothesis that, while sensitive to different aspects of
      executive functioning in patients with schizophrenia, the Wisconsin Card Sorting
      Test (WCST) and the Stroop Test also measure the same construct, namely,
      inhibitory control. Specifically, our goal was to confirm and extend previous
      findings [A. Rossi, E. Daneluzzo, P. Mattei, M. Bustini, M. Cassachia, P.
      Stratta, Wisconsin Card Sorting Test and Stroop performance in schizophrenia: a
      shared construct, Neurosci. Lett. 226 (1997) 87-90] by demonstrating the
      independence of this construct from other abilities necessary to successfully
      perform the tasks. More importantly, we sought to improve on this previous study
      by eliminating the influence of the variance of speed of responding. We examined
      55 patients with schizophrenia and initially found that performance on the Stroop
      Color-Word condition could, indeed, be predicted only by the percentage of
      perseverative errors on the WCST, and not variables reflective of other cognitive
      skills, thus replicating and extending previous findings. Once we removed the
      influence of speed of responding from our measure, however, thus isolating the
      inhibitory process, this finding disappeared. Therefore, our findings highlight
      the importance of isolating the individual components of interest from complex
      measures before drawing conclusions regarding the cognitive processes underlying
      particular test performance.

PMID- 17030095
TI  - Classical conditioning and expectancy in placebo hypoalgesia: a randomized
      controlled study in patients with atopic dermatitis and persons with healthy
      skin.
AB  - The effectiveness of placebos is unchallenged. However, it is still not clear on
      which mechanisms the placebo effect is based. Besides expectancy theories,
      classical conditioning is discussed as a major explanatory model. In an
      experimental conditioning design we tested 96 participants, 48 with atopic
      dermatitis (24 male, 24 female) and 48 with healthy skin (24 male and 24 female).
      All of them received a neutral ointment with a different briefing ("pain-reducing
      ointment" versus "neutral ointment"). Electrical pain stimuli were subsequently
      applied, which selectively induce a painful sensation. In the case of the
      learning condition (classical conditioning) and unbeknown to the participants,
      the intensity of the pain stimulus was reduced by 50% after the ointment had been
      applied. The study addressed the question whether the pain experienced by the
      patients with atopic dermatitis could be reduced through a placebo effect and
      whether the placebo effect was achieved through expectancy or through a process
      of classical conditioning or both. The results indicate that a placebo effect is
      achieved via expectancy and classical conditioning. However, conditioning
      processes seem to be necessary for a longer lasting effect. The extent of this
      effect seemed to be greater in atopics than in healthy controls. Expectancy,
      achieved through verbal instruction, might also be seen as a conditioned stimulus
      that reactivates earlier stimulus associations.

PMID- 17030096
TI  - Analgesic action of gabapentin on chronic pain in the masticatory muscles: a
      randomized controlled trial.
AB  - Chronic masticatory myalgia (CMM) can be defined as constant pain in the
      masticatory muscles for more than 6 months and is influenced by the central
      nervous system. The antiepileptic agent gabapentin acts centrally and is used for
      managing different types of chronic pain conditions. The objective of this study
      was to evaluate the analgesic action of gabapentin on CMM. In this 12-week
      randomized controlled clinical trial 50 patients were randomly allocated into two
      study groups: 25 received gabapentin and 25 received placebo. The outcome
      measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI)
      and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty
      six patients completed the study. Gabapentin showed to be clinically and
      statistically superior to placebo in reducing pain reported by patients
      (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia
      (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily
      functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded
      from this study that gabapentin is effective for the management of CMM.

PMID- 17030097
TI  - Environmental exposure to bacteria and viruses may provide oncolytic protection
      against cancers, and declining exposure to infections may contribute to a rising
      incidence of cancer.
AB  - Over the past century, the incidence of cancer rose markedly in developed
      countries. Many underlying factors are known, but not all of them. Over the same
      century, advances in public health and hygiene practically eradicated many
      infectious illnesses, and exposure to some untargeted infectious agents has also
      declined. There are reasons to suspect that these two trends are linked. Although
      some viruses and one bacterium are known to be oncogenic, a high percentage of
      infectious agents, 71% of viruses tested in one study, have shown oncolytic
      properties. Some of these agents have minimal or no clinical consequences, and
      some are - or were - quite ubiquitous. Many types of cancer are unusually
      susceptible to several different agents, sometimes 10-1000 times more susceptible
      than normal cells. When wild-type or attenuated viruses are used to treat cancer,
      they are often more effective with smaller tumors, and it may be that nascent,
      undetectable cancers are especially vulnerable. Environmental exposure to
      bacteria and viruses may provide natural protection from cancer by attacking it
      at this stage, or inducing the body to do so. Immunity to an infectious agent can
      attenuate its oncolytic effect, but generally does not stop it, so both initial
      and repeated exposures may be protective. As more direct evidence, treatment of
      animals with selected live virus vaccines has provided protection from cancer,
      and in humans, exposure to two specific infectious agents is known to correlate
      with a reduced risk of cancer. The significant decline in exposure to infectious
      agents over the past century may have inadvertently weakened this naturally
      protective mechanism, driving cancer rates up. There is considerable research on
      the impact of oncogenic agents, but surprisingly little regarding the impact of
      oncolytic agents on cancer rates. An understanding of the relationship between
      natural infections and the suppression of cancer may lead to prophylactic
      measures against cancer, improved public health policies regarding vaccination
      programs and hygiene, and greater insight into cancer treatment as well.

PMID- 17030098
TI  - Hygiene hypothesis and protection against asthma in infants: spending time in the
      countryside encountering natural allergens may boost maternal immunity.

PMID- 17030099
TI  - Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.
AB  - Body weight loss is common in cancer patients, and is often associated with poor
      prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is
      used in head and neck cancers (HNC) either as a primary treatment or as an
      adjuvant therapy to surgery. Patients with HNC are most susceptible to
      malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro
      inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL
      1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have
      been all associated with the development of both anorexia and oral mucositis.
      Radiation-induced mucositis occurs in almost all patients, who are treated for
      HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide,
      which up-regulates body weight through appetite control, increase food intake,
      down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin
      inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which
      may cause oral mucositis and aneroxia, which are the results of weight loss. Thus
      weight loss during RT is an early indicator of nutritional decline, we propose
      that recombinant ghrelin used prophylactically could be useful as an appetite
      stimulant; and preventive of mucositis because of its anti-inflammatory effect,
      it might help patients maintain weight over the course of curative RT of the HNC
      and can improve specific aspects of QOL. This issue warrants further studies.

PMID- 17030100
TI  - Abdominal aortic aneurysm and cerebral aneurysm present different pathological
      evolutions and responses to pharmacological therapy.
AB  - Over-degradation of extracellular components by matrix metalloproteinases (MMPs)
      has been implicated as an important characteristic during the pathological
      evolution of the abdominal aortic aneurysm (AAA) and cerebral aneurysm (CA),
      which contribute to progressive dilation of vascular wall. However, mRNA and
      protein expression of local rennin-angiotensin system (RAS) components are found
      down-regulated in CA walls, which is contrary to long-holding concept that local
      RAS will be activated in response to increased hemodynamic stress and contributes
      to thickening of arterial wall. Similarly, MMPs inhibition by doxycycline
      effectively ameliorate AAA expansion in basic and clinical researches, but can
      not reduce the incidence of CA formation in rat. These evidences may suggest that
      suppression of RAS favors the regression of AAA, but at an increased risk of CA
      rupture. As the strategies of RAS blockade have became the optimal
      antihypertensive drugs of choice in clinical arena, the discrepant responses to
      pharmacologic intervention of AAA and CA should be received considerable
      attentions, due to their high prevalence in hypertensive population. Here we
      proposed that AAA and CA, outward remodeling of elastic and muscular arteries
      respectively, presented with different pathological evolutions and distinct
      responses to drug intervention, i.e., RAS and MMPs inhibition. It can not be
      excluded that the potentially deleterious effects of RAS inhibition on CA may be
      masked by the beneficial action of controlled blood pressure, and the propagation
      of CA will be exacerbated once suboptimal dose have been prescribed, or under the
      condition of stress, even drug withdrawal. If the paradoxical outcomes of these
      two kinds of arterial remodeling were proven true in basic research, clinical use
      of RAS blockade should be prudent in hypertensive patients, and routine
      procedures to detect the existence of CA should be considered. Therefore, in
      depth investigation in their responses to pharmacological approaches will provide
      us with more insights into the pathogenesis of arterial aneurysm.

PMID- 17030101
TI  - Development of a PCR to diagnose BLV genome in frozen semen samples.
AB  - The sanitary and economic impact of BLV infection is associated with the
      interference in the international movement of cattle and their germ plasm.
      Although experimental data support the improbability that semen from BLV-positive
      bulls could infect recipient cows, restriction for commercialization of semen
      from infected animals is still present. The objective of this work was to
      standardize a PCR assay to diagnose the presence of BLV genome in frozen semen
      samples. The developed methodology involves the amplification of an internal
      fragment of gag gene. The limit of detection of this technique was six viral
      particles, using gag-PCR followed by hybridization analysis. Frozen semen samples
      from seropositive bulls were analyzed. It was possible to detect proviral DNA in
      9 out of 173 samples. Additionally, a biological test in susceptible sheep was
      performed in order to evaluate the transmission of BLV genome by semen from
      seropositive animals. This data strongly suggest that semen from seropositive
      bulls that resulted negative by PCR can be used for artificial insemination (AI),
      accompanied by proper collection protocols. The development of this PCR assay
      constitutes a valuable diagnostic tool to determine the BLV-free status of frozen
      semen samples used for AI.

PMID- 17030102
TI  - Isoniazid-induced hepatotoxicity in rat hepatocytes of gel entrapment culture.
AB  - Gel entrapment culture of rat hepatocytes in hollow fibers were evaluated as a
      potential in vitro model for studies on isoniazid-induced hepatotoxicity. After
      exposure to isoniazid (0.11 mM and 1.1 mM) for 24-96 h, gel entrapped hepatocytes
      were more severely damaged than hepatocyte monolayers according to the assays on
      methyl thiazolyl tetrazolium (MTT) reduction, intracellular glutathione (GSH)
      content, reactive oxygen species (ROS) levels, and albumin secretion.
      Furthermore, CYP 2E1 activity detected by 4-nitrocatechol (4-NC) formation
      maintained at least 7 days in gel entrapped hepatocytes but decreased to an
      undetectable level within 2 days in hepatocyte monolayer. And the addition of CYP
      2E1 inhibitor, diethyl-dithiocarbamate (DDC), significantly reduced isoniazid
      induced GSH depletion in gel entrapped hepatocytes. In addition, the protective
      effects of N-acetylcysteine (NAC), GSH, liquorice extract and glycyrrhizic acid
      (GA), a purified compound from liquorice extract, against isoniazid
      hepatotoxicity were clearly observed in gel entrapped hepatocytes at 72 h
      incubation. Overall, gel entrapped hepatocytes were more susceptible to isoniazid
      induced hepatotoxicity than hepatocyte monolayers by a possible mechanism that
      higher CYP 2E1 activity in gel entrapped hepatocytes could enhance isoniazid
      toxicity. This indicates that gel entrapped hepatocytes in hollow fibers could be
      a more effective model than hepatocyte monolayer for hepatotoxicity research in
      vitro.

PMID- 17030103
TI  - Change in serum undercarboxylated osteocalcin concentration in bilaterally
      oophorectomized women.
AB  - OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC)
      concentrations, bone turnover markers and spine bone mineral density (BMD) in
      women who had undergone bilateral oophorectomy during the premenopausal period.
      METHODS: The study population comprised 141 bilaterally oophorectomized and 32
      premenopausal women for a cross-sectional study. The longitudinal study consisted
      of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum
      concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase
      (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a
      bone resorption marker and serum parathyroid hormone (PTH) concentration were
      measured. RESULTS: Serum concentration of ucOC in women at 1 month after
      bilateral oophorectomy was significantly (p<0.05) higher than that in
      premenopausal women and the high level was sustained after surgical menopause. On
      the other hand, serum OC concentration at 1 month after surgical menopause was
      not different from that in premenopausal women. In the longitudinal study, serum
      ucOC concentration at 1 month after surgical menopause was significantly (p<0.05)
      increased compared to that before bilateral oophorectomy, while serum OC
      concentrations before and at 1 month after surgical menopause were not
      significantly different. CONCLUSION: The results of this study showed that serum
      ucOC concentration rapidly increases in women after bilateral oophorectomy and
      that change in serum ucOC concentration after surgical menopause is different
      from change in serum OC concentration.

PMID- 17030104
TI  - Dry eye in post-menopausal women using hormone replacement therapy.
AB  - PURPOSE: To evaluate the effect of hormone replacement therapy (HRT) on dry eye
      in post-menopausal women. METHODS: Forty post-menopausal women with dry eye (20
      patients, group 1) and without dry eye (20 patients, group 2), and planning to
      receive HRT (estrogen plus progesterone), were recruited as the study groups.
      Forty age-matched untreated women were enrolled as controls (group 3 with dry
      eye, 5 patients; group 4 without dry eye, 35 patients). Patients having at least
      one of the symptoms (dryness, itching, photophobia, foreign body sensation, and
      tearing) together with two of the tests with positive results for dry eye (tear
      film break-up time (BUT), fluorescein staining of the cornea, analysis of the
      meibomian gland, and Schirmer I test) in both eyes were considered dry eye
      positive. Hormonal assay for follicle stimulating hormone, luteinizing hormone,
      estradiol, and free testosterone was performed. Dry eye statuses in the groups
      were evaluated statistically. RESULTS: Four patients with incomplete follow-up
      data were excluded. HRT use increased estradiol levels in the groups. Mean ages
      of patients (50.2+/-4.8 and 50.7+/-3.9 years, and 50.0+/-4.6 and 53.0+/-3.9
      years) were similar (p=0.67). Duration of menopause in groups 1 and 2 (3.2+/-2.2
      and 1.4+/-1.2 years; p=0.01), and in groups 3 and 4 (3.0+/-1.6 and 1.7+/-1.3
      years; p=0.014) were different. At the third month examinations, all of the
      patients in group 1, and 11 patients (61.1%) in group 2 had dry eye (p=0.003).
      CONCLUSION: Duration of menopause and use of HRT may increase the incidence of
      dry eye in post-menopausal woman.

PMID- 17030105
TI  - Essential oil of Pterodon polygalaeflorus inhibits electromechanical coupling on
      rat isolated trachea.
AB  - The present work studied the effects of the essential oil of Pterodon
      polygalaeflorus (EOPP), a plant used to treat bronchitis and amigdalytis, on rat
      airway smooth muscle in vitro. In Ca(2+)-containing medium, EOPP (100-1300
      microg/ml) inhibited preferentially high KCl- than 5-HT-induced muscle
      contractions in a concentration-dependent fashion, but did affect neither basal
      muscle tension nor ACh-induced contractions. In preparations maintained in either
      60 mM K(+) or 10 microM ACh in Ca(2+)-free medium, EOPP (100, 600 and 1300
      microg/ml) inhibited maximum contractile response induced by cumulative Ca(2+)
      addition (0.1-20 mM). Verapamil (10, 30 and 100 microg/ml), a Ca(2+) channel
      blocker, also inhibited Ca(2+)-induced concentration-effect curve in presence of
      ACh in Ca(2+)-free medium, whilst it was ineffective to decrease cholinergic
      contractions in Ca(2+)-containing medium. In presence of 150 mM K(+) in Ca(2+)
      containing medium, EOPP (1300 microg/ml) did not reversed ACh-induced
      contractions. In contrast, under similar conditions, EOPP almost fully relaxed
      cholinergic contractions of tracheal smooth muscle in Ba(2+)-containing medium.
      In medium containing 10 mM tetraethylammonium and 2 mM Ba(2+) instead of Ca(2+),
      both EOPP (1300 microg/ml) and verapamil (approximately 5 microg/ml)
      significantly decreased ACh-induced contractions. Thus, in rat isolated trachea,
      EOPP induces inhibitor effects on contractions preferentially triggered by an
      electromechanical coupling mode.

PMID- 17030106
TI  - Further evidence of in vitro production of gamma-hydroxybutyrate (GHB) in urine
      samples.
AB  - This study was designed to supplement previous studies that documented in vitro
      production of gamma-hydroxybutyrate (GHB) in urine samples. Urine samples were
      provided by subjects who reported that they had never used GHB (n=31). The
      specimens were stored under standard conditions of refrigeration (5 degrees C)
      without any preservatives added. All specimens were repeatedly analyzed for the
      presence of endogenous GHB over a 6-month period using a previously reported
      headspace GC-MS method. Significant elevations in GHB were observed in many of
      the urine samples as storage time increased. As a result, the in vitro production
      of GHB may increase the apparent GHB concentrations in urine during storage. This
      potential for an artificial increase in GHB concentration must be appreciated
      when establishing the threshold between endogenous and exogenous concentrations
      of GHB.

PMID- 17030107
TI  - Zinc-binding proteins (metallothionein and alpha-2 macroglobulin) and
      immunosenescence.
AB  - Zinc is a relevant trace element for the efficiency of the entire immune system.
      The binding of zinc with some proteins, such as metallothioneins (MT) and alpha-2
      macroglobulin (alpha-2M) is crucial for the immune efficiency during ageing and
      in age-related diseases, because these proteins may be involved in antagonistic
      pleiotropic effects. Indeed, the presence of chronic inflammation during ageing,
      generally, induces overexpression of these proteins that, due to their original
      biological function in fighting stressor agents, continuously sequester
      intracellular zinc. As a consequence, a low zinc ion availability may appear in
      aged organisms leading to impairments of the immune response at thymic and
      extrathymic levels with the risk of the appearance of age-related diseases.
      Therefore, MT and alpha-2M turn from protective in "young-adult age" to harmful
      agents in "ageing" following the basic assumption of an evolutionary theory of
      ageing, named the "antagonistic pleiotropy", which suggests that a trade off
      between early beneficial effects and late negative outcomes can occur at a
      genetic and molecular level. On the other hand, some polymorphisms of MT (MT2A)
      and alpha-2M have been associated with atherosclerosis or Alzheimer disease,
      respectively. Physiological zinc supplementation in elderly restores the thymic
      endocrine activity and innate immune response (NK cell cytotoxicity) and
      increases the survival rate in old mice. Therefore, zinc supplementation is
      useful to achieve health longevity because these zinc-binding proteins may regain
      their original protective task against oxidative damage with, thus, a beneficial
      impact on immune response.

PMID- 17030108
TI  - Influence of mammographic density on the diagnostic accuracy of tumor size
      assessment and association with breast cancer tumor characteristics.
AB  - PURPOSE: The accuracy of breast cancer staging involves the estimation of the
      tumor size for the initial decision-making in the treatment. We investigated the
      accuracy of tumor size estimation and the association between tumor
      characteristics and breast density (BD). MATERIALS AND METHODS: A total of 434
      women with a primary diagnosis of breast cancer were included in this prospective
      study at a specialist breast unit. Estimated tumor characteristics included tumor
      size, nodal status, estrogen/progesterone receptor status, Ki-67, HER2/neu,
      vascular invasion. Radiomorphological data included tumor size as assessed by
      mammography, breast ultrasonography, and clinical examination, and American
      College of Radiology (ACR) categories for BD. RESULTS: BD did not have a
      significant impact on the assessment of tumor size using breast ultrasound
      (deviation from ACR categories 1-4: 0.55-0.68 cm; P=0.331). The deviation in
      mammography was significantly different dependent on BD (0.42-0.9 cm; P<0.001).
      The clinical examination was not affected by BD. Age and tumor size were the only
      parameters associated with a denser breast in the multivariate analysis. Older
      women were less likely to have dense breasts (odds ratio 0.157 for women aged
      >or=70 years), and patients with larger tumors were less likely to have dense
      breasts (adjusted OR 0.36 for tumors>2 cm). CONCLUSION: Breast ultrasonography is
      more accurate than mammography for assessing tumor size in breasts with a higher
      BD. The difference in tumor size assessment needs to be taken into consideration
      in the design of clinical trials and treatment decisions.

PMID- 17030109
TI  - HPLC-NMR with severe column overloading: fast-track metabolite identification in
      urine and bile samples from rat and dog treated with [14C]-ZD6126.
AB  - The subject of this study was the determination of the major urinary and biliary
      metabolites of [(14)C]-ZD6126 following i.v. administration to female and male
      bile duct cannulated rats at 10 mg/kg and 20 mg/kg, respectively, and male bile
      duct cannulated dogs at 6 mg/kg by HPLC-NMR spectroscopy. ZD6126 is a
      phosphorylated pro-drug, which is rapidly hydrolysed to the active metabolite,
      ZD6126 phenol. The results presented here demonstrate that [(14)C]-ZD6126 phenol
      is subsequently metabolised extensively by male dogs and both, male and female
      rats. Recovery of the dose in bile and urine was determined utilising the
      radiolabel, revealing biliary excretion as the major route of excretion (93%) in
      dog, with the majority of the radioactivity recovered in both biofluids in the
      first 6 h. In the rat, greater than 92% recovery was obtained within the first 24
      h. The major route of excretion was via the bile 51-93% within the first 12 h.
      The administered phosphorylated pro-drug was not observed in any of the excreta
      samples. Metabolite profiles of bile and urine samples were determined by high
      performance liquid chromatography with radiochemical detection (HPLC-RAD), which
      revealed a number of radiolabelled components in each of the biofluids. The
      individual metabolites were subsequently identified by HPLC-NMR spectroscopy and
      HPLC-MS. In the male dog, the major component in urine and bile was the [(14)C]
      ZD6126 phenol glucuronide, which accounted for 3% and 77% of the dose,
      respectively. [(14)C]-ZD6126 phenol was observed in urine at 1% of dose, but was
      not observed in bile. A sulphate conjugate of demethylated [(14)C]-ZD6126 phenol
      was identified in bile by HPLC-NMR and confirmed by HPLC-MS. In the rat, the bile
      contained two major radiolabelled components. One was identified as the [(14)C]
      ZD6126 phenol glucuronide, the other as a glucuronide conjugate of demethylated
      [(14)C]-ZD6126 phenol. However, a marked difference in the proportions of these
      two components was observed between male and female rats, either due to a sex
      difference in metabolism or a difference in dose level. The glucuronide conjugate
      of the demethylated [(14)C]-ZD6126 phenol was present at higher concentration in
      the bile of male rats (4-34%), while the phenol glucuronide was present at higher
      concentration in the bile of female rats (8-70%) over a 0-6 h collection period.
      A third component was only observed in the bile samples (0-6 h and 6-12 h) of
      male rats. This was identified as being the same sulphate conjugate of
      demethylated [(14)C]-ZD6126 phenol as the one observed in dog bile. The rat
      urines contained two main metabolites in greatly varying concentrations, namely
      the demethylated [(14)C]-ZD6126 phenol glucuronide and the glucuronide of [(14)C]
      ZD6126 phenol. Again, the differences in relative amounts between male and female
      rats were observed, the major metabolite in the urines from male rats being the
      demethylated [(14)C]-ZD6126 phenol (0-17% in 0-24 h), whilst the phenol
      glucuronide, accounting for 0.5-50% of the dose over 0-24 h, was the major
      metabolite in females. Methanolic extracts of the pooled biofluid samples were
      submitted for HPLC-NMR for the quick identification of the major metabolites.
      Following a single injection of the equivalent of 6-28 ml of the biofluids
      directly onto the HPLC-column with minimal sample preparation, the metabolites
      could be largely successfully isolated. Despite severe column overloading, the
      major metabolites of [(14)C]-ZD6126 could be positively identified, and the
      results are presented in this paper.

PMID- 17030110
TI  - Thyroid hormone deficiency changes the distribution of oligodendrocyte/myelin
      markers during oligodendroglial differentiation in vitro.
AB  - Myelination depends on the proper differentiation of oligodendrocytes and several
      factors may influence this event. For instance, thyroid hormone (T3) affects the
      timing of differentiation and regulates the expression of several enzymes
      involved in the synthesis of complex lipids and in the expression of some myelin
      structural proteins. We investigated the effect of T3 deficiency on
      oligodendroglial differentiation and in the distribution of
      oligodendrocyte/myelin proteins 2'3'-cyclic nucleotide 3'-phosphodiesterase
      (CNPase) and myelin basic protein (MBP). Oligodendroglial-enriched cultures were
      obtained from cerebra of neonate rats grown in a modified medium. The T3
      deficient status was induced by using medium devoid of T3. We observed a delay,
      in T3-deficient cultures, in oligodendroglial maturation characterized by less
      extensive processes and membrane vellum than in controls. In control cultures,
      CNPase immunoreactivity was punctated, showing cell bodies and processes at
      earlier stages and redistribution to cytoskeleton vein-like structures in later
      stages. In T3-deficient cultures, CNPase remained in a punctated pattern and only
      at 10 days in vitro we observed CNPase redistribution to the presumptive
      cytoskeleton vein-like structures. MBP in control cultures was distributed
      through the whole cell body and processes whereas in T3-deficient cultures, MBP
      immunoreactivity was concentrated in the perinuclear region. These results
      reinforce the hypothesis that T3 is an important factor in oligodendrocyte
      differentiation, particularly regarding the distribution of myelin proteins.

PMID- 17030111
TI  - Cognitive function in adults with type 2 diabetes and major depression.
AB  - The aim of this study was to identify characteristics of neuropsychological
      functioning among type 2 diabetic adults with and without major depression.
      Twenty type 2 diabetics with major depression, 20 non-depressed type 2 diabetics
      and 34 controls without diabetes or depression were compared. A mixed effects
      repeated measures analysis of covariance indicated significant differences in
      overall cognitive functioning between diagnostic groups, specifically depressed
      diabetics demonstrated greater cognitive dysfunction than controls. Further
      comparisons indicated that depressed diabetics performed significantly worse than
      non-depressed diabetics in attention/information processing speed. Relative to
      controls, depressed diabetics performed significantly worse in
      attention/information processing speed and executive functioning, while there was
      a trend for non-depressed diabetics to perform worse in executive functioning.
      These findings suggest that depression negatively impacts cognitive performance
      among adults with type 2 diabetes, which may have implications for neural
      circuitry underlying cognitive and mood changes in diabetic patients.

PMID- 17030112
TI  - Comparative proteomic profiles and the potential markers between Burkholderia
      pseudomallei and Burkholderia thailandensis.
AB  - Burkholderia pseudomallei is a bacterial pathogen causing the melioidosis
      disease, which is predominantly found in tropical areas of Southeast Asia and
      Northern Australia. Burkholderia thailandensis is a closely related species to B.
      pseudomallei but it is non-pathogenic species. In this study, we have constructed
      a proteome reference map of B. pseudomallei at the stationary phase of growth by
      using two-dimensional gel electrophoresis with a pH 4-7 immobilized pH gradient
      combined with matrix-assisted laser desorption ionization time of flight mass
      spectrometry. Approximately 550 spots could be detected by Coomassie brilliant
      blue G-250 staining, and 88 spots representing 77 unique proteins were
      identified. Eleven of the gene products were found in multiple spots indicating
      as isoforms. In attempt to detect distinctive expressed proteins between a
      virulent and a non-virulent species, the use of comparative proteomic profiles
      under the same condition were performed. We could identify more than 20 different
      spots. Twelve out of 14 spots are detected in B. pseudomallei and six proteins
      have been identified and indicated that they are involved in virulent characters
      of bacteria. Two hypothetical proteins were expressed and found only in B.
      pseudomallei. These proteins are potential markers to distinguish between these
      two species. Our study also provides a useful information of global intracellular
      protein expression and is a valuable starting point for analyzing a proteomic
      pathogenicity of the bacterial pathogen.

PMID- 17030113
TI  - Muscadine grape products intake, diet and blood constituents of non-diabetic and
      type 2 diabetic subjects.
AB  - OBJECTIVE: Red wines and grape juices contain polyphenolics with antioxidant and
      antiplatelet properties that may be protective against oxidative stress leading
      to hypertension, insulin resistance, and type 2 diabetes (T2D). This study
      evaluated the effects of supplementing meals of subjects with 150 mL of muscadine
      grape juice (MJ), muscadine grape wine (MW), and dealcoholized muscadine grape
      wine (Dz-W) on glycemic indices, blood constituents, lipid profile,
      anthropometric, and nutrient intakes of healthy and T2D subjects over a 28-d
      period. METHODS: Subjects with T2D were assigned to take MJ, MW, or Dz-W. Non
      diabetics consumed MJ and controls were given no test drinks. Several metabolic
      indicators associated with diabetic conditions were measured at baseline and
      repeated after 28 d. RESULTS: Diabetics given MW and Dz-W showed lower levels of
      blood glucose, insulin, and glycated hemoglobin, indicating better glycemic
      control. Elevated dietary vitamin C and E levels were observed in diabetics given
      Dz-W, indicating improved antioxidant status. Decreased red blood cell membrane
      saturated fatty acids and increased mono- and polyunsaturated fatty acids for
      subjects with T2D given MW suggested improved membrane fluidity. Lower sodium and
      chloride values for subjects T2D given MW suggested lower risk for developing
      hypertension. Improved hepatic conditions were noted by decreases in alanine
      aminotransferase and aspartate aminotransferase among subjects with T2D given MW,
      indicating better insulin sensitivity and decreased tendency toward impaired
      liver function. CONCLUSION: Daily intake of 150 mL of MW or Dz-W with meals
      improved several metabolic responses among diabetics compared with diabetics
      given MJ.

PMID- 17030115
TI  - Effects of constitutive deletion of opioid receptors on the basal densities of
      Fas and Fas-associated protein with death domain (FADD) in the mouse brain: a
      delta-opioid tone inhibits FADD.
AB  - The acute effects of opiate drugs and opiate addiction have been associated with
      modulation of Fas/FADD (Fas-Associated protein with Death Domain) signaling
      complex in the rat brain. This study investigated the possible existence of
      endogenous opioid tones regulating the basal activities of Fas receptor forms and
      FADD in the brain, using gene-targeted mice lacking mu-, delta- or kappa-opioid
      peptide receptors (KO mice). In mu-KO mice, but not in delta- or kappa-KO mice,
      the basal immunodensity of native Fas (35 kDa monomeric form) was decreased in
      the cerebral cortex (33%) when compared with WT littermates. In delta-KO mice,
      but not in mu- or kappa-KO mice, the basal content of 120 kDa Fas aggregates
      (complexes of monomers relevant in Fas signaling) was markedly increased in the
      cortex (93%). In contrast, no differences between genotypes were observed in the
      basal expression of glycosylated Fas (51/48/45 kDa forms). Notably, the basal
      content of FADD (the adaptor protein that couples Fas to caspases and transmits
      the death signal) was increased in the cerebral cortex of delta-KO mice (48%),
      but not in mu- or kappa-KO mice. In addition, the basal content of phosphorylated
      FADD at Ser191 (the relevant species of FADD implicated in nonapoptotic signals)
      was also upregulated in the cortices of delta-opioid receptor KO mice (6.5-11.0
      fold). The results suggest that mu-receptors tonically stimulate (through
      endogenous opioid peptides) the activation of native Fas, whereas delta-receptors
      tonically inhibit the expression of Fas aggregates and that of FADD and
      phosphorylated FADD (Ser191) in the mouse brain. These data are in line with the
      acute opposite modulation of Fas and FADD induced by mu- and delta-opiate
      agonists, and strongly support the notion of an anti-apoptotic delta-opioid tone
      that restrains Fas signaling.

PMID- 17030114
TI  - Effect of calcium fortified milk supplementation with or without vitamin K on
      biochemical markers of bone turnover in premenopausal women.
AB  - OBJECTIVE: We compared the effect of supplementation with a fortified skimmed
      milk product (high calcium skim milk) with or without added phylloquinone
      (vitamin K(1)) on markers of bone formation and resorption in premenopausal
      women. METHODS: Eighty-two women 20 to 35 y of age were randomly allocated to
      three groups. Two groups received two daily servings of high calcium skim milk
      (1000 mg/d of extra calcium) with or without added phylloquinone (80 microg/d)
      for 16 wk, and a third control group received no supplementation. Bone density
      was assessed at baseline and the bone markers, total osteocalcin, type I N
      terminal procollagen peptide, and cross-linked C-telopeptide of type I collagen
      were measured at baseline and at weeks 2, 12, and 16. Serum phylloquinone and
      undercarboxylated osteocalcin were measured in the control and vitamin K
      supplemented groups at weeks 0 and 16. RESULTS: Baseline values for age, body
      mass index, and bone density did not differ across groups. In vitamin K
      supplemented women, mean serum phylloquinone concentrations increased from 0.27
      to 0.76 microg/L (P < 0.05) and undercarboxylated osteocalcin concentrations
      decreased from 9.68 to 4.46 microg/L (P < 0.05) over 16 wk. Plasma cross-linked C
      telopeptide of type I collagen, total osteocalcin, and type I N-terminal
      procollagen peptide levels decreased significantly in both supplemented groups
      compared with the control group over 16 wk (cross-linked C-telopeptide of type I
      collagen >30%, total osteocalcin and type I N-terminal procollagen peptide >15%).
      CONCLUSION: Fortified milk supplementation in premenopausal women reduced bone
      turnover significantly. Phylloquinone fortification substantially improved
      vitamin K status but had no demonstrable additive effect on bone turnover in this
      short-term study.

PMID- 17030116
TI  - Determinative role of Wnt signals in dorsal iris-derived lens regeneration in
      newt eye.
AB  - We have previously shown that lens regeneration from the pigmented epithelium of
      the dorsal iris in the adult newt eye proceeds in two steps after lens removal or
      intraocular FGF2 injection. The FGF2-dependent proliferation of iris pigmented
      epithelium and activation of early lens genes that occur over the entire
      circumference of the iris comprise the first step, while subsequent dorsally
      confined lens development marks the second step. Here, we investigated the
      expression of Wnt and Wnt receptor Frizzled genes in lens-regenerating iris
      tissues. Wnt2b and Frizzled4 were activated only in the dorsal half of the iris
      in synchrony with the occurrence of the second step, whereas Wnt5a and Frizzled2
      were activated in both halves throughout the period of the first and second
      steps. Cultured explants of the iris-derived pigmented epithelium in the presence
      of FGF2 underwent dorsal-specific lens development fully recapitulating the in
      vivo lens regeneration process. Under these conditions, Wnt inhibitors Dkk1,
      which specifically inhibits the canonical signal pathway, and/or sFRP1 repressed
      the lens development, while exogenous Wnt3a, which generally activates the
      canonical pathway like Wnt2b, stimulated lens development from the dorsal iris
      epithelium and even caused lens development from the ventral iris epithelium,
      albeit at a reduced rate. Wnt5a did not elicit lens development from the ventral
      epithelium. These observations indicate that dorsal-specific activation of Wnt2b
      determines the dorsally limited development of lens from the iris pigmented
      epithelium.

PMID- 17030117
TI  - Amygdala activation in the processing of neutral faces in social anxiety
      disorder: is neutral really neutral?
AB  - Previous research has suggested that Social Anxiety Disorder (SAD) is associated
      with a tendency to interpret ambiguous social stimuli in a threatening manner.
      The present study used event-related functional magnetic resonance imaging to
      examine patterns of neural activation in response to the processing of neutral
      facial expressions in individuals diagnosed with SAD and healthy controls (CTLs).
      The SAD participants exhibited a different pattern of amygdala activation in
      response to neutral faces than did the CTL participants, suggesting a neural
      basis for the biased processing of ambiguous social information in SAD
      individuals.

PMID- 17030118
TI  - Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo
      evaluation of drug release properties.
AB  - Drug eluting beads that release irinotecan in a controlled manner may be useful
      for application in the chemoembolization of colorectal cancer metastases to the
      liver. In this study, irinotecan drug eluting beads were prepared with loadings
      up to 50 mg drug/mL hydrated beads. Drug loading was via an ion-exchange
      mechanism with sulfonate binding sites in the bead. Release in vitro was shown to
      be sustained and dependent upon the presence of ions in the elution medium, drug
      loading and bead size. Drug elution in PBS was controlled by solute diffusion
      within the beads and gave rise to values for the diffusion coefficient, D, of
      between 2.4x10(-9) and 1.4x10(-7) cm(2)s(-1). The beads were shown to decrease in
      size (by a maximum 25-30%), and concomitantly their modulus of compression
      increased (from approximately 27 kPa to a maximum of about 49 kPa), with
      increasing drug loading. This did not however, influence their ability to be
      suspended homogeneously in contrast agent or delivered through a microcatheter.
      Following porcine hepatic artery embolization, maximum plasma levels were 70-75%
      lower for both irinotecan and SN-38 compared to intraarterial bolus
      administration, with peak levels observed at 2 and 5 min after completion of the
      embolization procedure. The in vivo data were shown to correlate well with the in
      vitro release measured using a T-apparatus model of embolization.

PMID- 17030119
TI  - [Campylobacter jejuni and cytomegalovirus (CMV) infections in patients with the
      Guillain-Barre syndrome].
AB  - Guillain-Barre syndrome (GBS) is a rare disease triggered by postinfectious
      mechanisms. The disease concerns all ages, and is widely distributed around the
      world. The principal risks are respiratory failure, especially during the initial
      phase of the disease, and persisting deficit at long term. Among the infectious
      known agents, Campylobacter jejuni and CMV represent more than 40% of GBS causes.
      The clinical presentation, and the long-term prognosis of GBS related to these
      two etiologies are different. The physiopathological mechanisms of the nervous
      attack are probably also different. There is no proof, at this time, that anti
      infectious treatment can improve the prognosis. The treatment is based on the
      early use of immunomodulatory treatments like intravenous immunoglobulins or
      plasma exchanges.

PMID- 17030120
TI  - [A move meat beginning...and evolutive].
AB  - Food allergies are more and more numerous, and frequent in children at all ages.
      At any moment, a clinical manifestation, quickly evolutive and alarming, must
      need the help call at phone 15, and the intervention of a medical team of SMUR.
      The departmental, free, cell to 15 for all medical emergencies note a regular
      increase of these specific calls since ten years, as this following case report
      shows it.

PMID- 17030121
TI  - [Non IgE-mediated cow's milk allergy].

PMID- 17030122
TI  - Development of the neural crest: achieving specificity in regulatory pathways.
AB  - Recent studies have revealed the signaling pathways and downstream effectors
      involved in the specification of the neural crest. Neural crest cells are
      generated from a zone at the neurectoderm border in response to Wnt and BMP
      signals. BMP signals are involved in establishing a competency zone at the border
      of the neurectoderm, while subsequent Wnt signals specify neural crest cells.
      Combinations of transcription factors, including pax and msx gene products, act
      downstream of these pathways to integrate signals and establish the neural crest.
      Mechanisms are emerging for how specificity is generated from reiterated signals
      and effectors.

PMID- 17030123
TI  - Mitotic phosphatases: no longer silent partners.
AB  - Recent work has highlighted the important role played by protein phosphatase
      complexes in the regulation of mitosis from yeast to mammals. There have been
      important advances in defining the roles of the protein serine/threonine
      phosphatases PP1 and PP2A and the dual specificity protein tyrosine phosphatases
      CDC25 and Cdc14. Three independent studies defined a regulatory role for PP2A in
      the control of sister chromatid cohesion, involving a direct interaction with
      shugoshin. A chromatin targeting subunit has been identified for PP1 and the
      complex shown to play an essential role in chromosome segregation. Key regulatory
      residues within CDC25 have been mapped and its activity tied both to the initial
      activation of cyclin-dependent kinases at the centrosome and to DNA damage
      checkpoints. Novel roles have been defined for Cdc14, including regulation of
      rDNA and telomere segregation and participation in spindle assembly. These
      exciting advances show that protein phosphatases are not merely silent partners
      to kinases in regulating the control of cell division.

PMID- 17030125
TI  - An objective method for regularization of fiber orientation distributions derived
      from diffusion-weighted MRI.
AB  - Spherical deconvolution is an elegant method by which the orientation of crossing
      fibers in the brain can be estimated from a diffusion-weighted MRI measurement.
      However, higher resolution of fiber directions comes at the cost of higher
      susceptibility to noise. In this study, we describe the use of linear
      regularization of the fiber orientation distribution function by Damped Singular
      Value Decomposition. Furthermore, the degree of regularization is optimized on a
      voxel-by-voxel basis with no user interaction using Generalized Cross Validation.
      We find, by simulations, that regularization can improve the reliability of fiber
      orientation determination when the signal-to-noise ratio is low. Simulations and
      in vivo measurements indicate that spurious peaks of the fiber orientation
      distribution function in regions with low anisotropy largely disappear when
      regularization is introduced. The methods examined are fast enough to be used on
      a routine basis with diffusion MRI data sets and may improve estimation of water
      diffusion properties in heterogeneous white matter and boost reliability of fiber
      tracking through regions of brain with complex fiber geometry.

PMID- 17030124
TI  - Sonic hedgehog signaling in forebrain development and its interactions with
      pathways that modify its effects.
AB  - During the development of the nervous system and other organs in the embryo, a
      limited set of master signaling pathways are used repeatedly for induction,
      patterning and growth. Among these, the Sonic hedgehog (Shh) pathway is crucial
      for the development of many structures in the brain. How the context-specific
      interplay between these various signaling pathways produces distinct temporal and
      spatial outcomes is not clear. Resolving this problem is a major goal in the
      study of cell and organ development. Here, we focus on signaling events during
      dorso-ventral patterning of the embryonic forebrain in vertebrates. In
      particular, we discuss the role of the Shh pathway in this process and on its
      interactions with the FGF, retinoic acid and Nodal pathways and other information
      cascades that modify its effects.

PMID- 17030126
TI  - Subacromial plica as a cause of impingement in the shoulder.
AB  - The subacromial bursa is the largest bursa in the body. In 1934, Codman described
      the presence of subacromial plicae, similar to the suprapatellar plicae found in
      the knee. It is recognized that plicae in the knee can cause anterior knee pain
      with impingement against the patella in young persons. We investigated the
      possibility that a similar situation exists with plicae of the subacromial bursa.
      The aims of this study were to document the prevalence of bursal plicae seen at
      bursoscopy during arthroscopic subacromial decompression of the shoulder and to
      assess whether there is any pattern in the occurrence of these plicae, as well as
      the relationship to impingement lesions seen at bursoscopy. Between January 1996
      and July 2001, all cases undergoing arthroscopic decompression were evaluated for
      anatomic-pathologic changes of the subacromial bursa, including the presence of
      plicae and impingement lesions. A total of 1732 cases complying with inclusion
      criteria were recorded, with plicae observed in 104 (6.0%). The occurrence of
      plicae showed a highly significant younger age predilection (P = .0008, chi(2)
      test) but no differences between sexes or sides. The occurrence of subacromial
      plicae was highly associated with the combined severity of the impingement lesion
      on the acromial and bursal side. Plicae were most common in shoulders showing an
      impingement lesion on the cuff bursal side, with no impingement lesion on the
      acromial side. The odds of the impingement lesion being milder on the acromial
      side was 3.41 times higher in shoulders with a plica compared with shoulders
      without a plica. This suggests that impingement of the cuff may be due to the
      plica itself. This study is the first to describe the presence of subacromial
      plicae in living subjects and correlates with previous anatomic studies. The
      younger age predominance correlates with the findings of plicae in the knee. Our
      findings suggest that subacromial plicae may be a cause of impingement in young
      patients.

PMID- 17030127
TI  - Irreducible pulled elbow in an adult: a case report.

PMID- 17030128
TI  - The effect of total shoulder arthroplasty on self-assessed deficits in shoulder
      function in patients with capsulorrhaphy arthropathy.
AB  - The objective of this study was to characterize self-assessed functional deficits
      before and after total shoulder arthroplasty (TSA) in a consecutive series of 24
      patients treated for capsulorrhaphy arthropathy. Deficits were determined by use
      of the Simple Shoulder Test. The effects of age, type of original stabilization
      surgery, duration of time since the initial repair, and pattern of glenoid
      erosion were analyzed. Deficits were significantly reduced from 8.5 to 4 of 12
      SST items after TSA (P = .003). Items related to motion and function had the
      largest effect on improvement. Age did not affect results. There was a trend
      toward greater improvement in patients whose original stabilization was less than
      20 years previously (P = .06) and in those with concentric glenoid erosion (P =
      .06). A prior Bristow procedure was associated with the least improvement.
      Overall, TSA was an effective treatment for capsulorrhaphy arthropathy at midterm
      follow-up. Restoring range of motion appears to have the largest impact on
      improvement in function.

PMID- 17030129
TI  - Treatment of ligament laxity by electrothermal shrinkage or surgical plication: a
      morphologic and mechanical comparison.
AB  - Capsular plication or thermal shrinkage can be used to enhance surgical joint
      stabilization. We compared mechanical or morphologic properties of the medial
      collateral ligament of the rabbit knee treated by either bipolar radiofrequency
      electrothermal shrinkage or surgical plication. After 12 weeks, the medial
      collateral ligaments were procured from treated and contralateral knees to
      undergo viscoelastic (creep) testing, quantitative transmission electron
      microscopy, and immunohistochemistry. Creep strain in thermal (1.85% +/- 0.32%)
      and plicated (1.92% +/- 0.36%) ligaments was almost twice that of the control
      group (1.04% +/- 0.15%), although there was no difference between treatment
      modalities. The morphologic parameters of all 3 groups were significantly
      different (P < .001). The thermal ligaments demonstrated predominantly small
      fibrils, whereas the plicated group displayed an intermediate distribution of
      heterogeneous fibrils, suggesting a different pattern of remodeling. Viscoelastic
      properties are similar after thermal shrinkage or plication, though inferior to
      those of intact ligaments.

PMID- 17030130
TI  - Pre-operative radial arterial diameter predicts early failure of arteriovenous
      fistula (AVF) for haemodialysis.
AB  - INTRODUCTION: Long term patency of arteriovenous fistula (AVF) is relevant to the
      management of end stage renal failure (ESRF) patients on haemodialysis (HD). We
      evaluated the role of routine radial arterial duplex for imaging radial artery
      before AVF formation to investigate the relationaship between radial artery
      internal diameter (ID) and AVF patency. METHODS: 21 patients with ESRF were
      examined by duplex sonography before AVF formation, 1 day, 1 week, 4 week and 12
      weeks post AVF formation. For assessment of AVF patency, patients were divided
      into 2 groups. Group-1, 11 patients with radial artery ID <1.5mm and Group-2, 10
      patients with radial artery ID >1.5mm. Measurement of radial artery blood inflow
      rate was calculated from mean blood flow velocity and vessel diameter. All AVFs
      were constructed on the forearm using autologous veins. RESULTS: In Group-1, 5
      patients (45%) showed immediate thrombosis of AVF graft. All patients in group-2
      had patent AVF at 12 weeks. Pre-AVF formation radial artery blood inflow rate
      between two groups was not significantly different (p=0.06). Radial artery blood
      inflow rate was consistently and significantly higher in group-2 at all later
      time points with p value of <0.01 (Mann Whitney test). CONCLUSION: There was a
      high failure rate of AVF with radial artery ID of <1.5mm. In the presence of
      small radial arteries primary access AVF in the upper arm should be considered.

PMID- 17030131
TI  - Haemodynamic and clinical assessment of lateral marginal vein excision in
      patients with a predominantly venous malformation of the lower extremity.
AB  - OBJECTIVE: The purpose of the present study was to determine the effects of the
      surgical excision of lateral marginal veins (LMVs) in patients with a venous
      malformation (VM) affecting the lower extremity. METHODS: Preoperative and
      postoperative air plethysmography (APG), CEAP classification C scores, and venous
      clinical severity scores (VCSS) of the 25 VM patients who underwent LMV excision
      were compared. RESULTS: After LMV excision, venous haemodynamic parameters
      revealed significantly increased ejection fraction (EF, 33.2 S.D.18.5% vs. 39.7
      S.D.21.2%, P=.020), and reduced venous volume (VV, 235.0 S.D.141.8 ml vs. 198.0
      S.D.114.1 ml, P=.016) and residual venous fraction (RVF, 62.4 S.D. 26.6% vs. 56.9
      S.D. 25.3%, P=.046). Clinical assessments of affected limbs revealed
      significantly improved mean CEAP C scores and VCSS (preoperative score, 4.4
      S.D.1.7 vs. postoperative score 2.4 S.D.1.7, P=.026) after LMV excision versus
      preoperative data. CONCLUSION: Haemodynamic and clinical improvements were
      observed in patients with lower extremity VM after LMV excision.

PMID- 17030132
TI  - How accurately can the parameters from a model of anisotropic 3He gas diffusion
      in lung acinar airways be estimated? Bayesian view.
AB  - In the framework of a recently proposed method for in vivo lung morphometry,
      acinar lung airways are considered as a set of randomly oriented cylinders
      covered by alveolar sleeves. Diffusion of (3)He in each airway is anisotropic and
      can be described by distinct longitudinal and transverse diffusion coefficients.
      This macroscopically isotropic but microscopically anisotropic model allows
      estimation of these diffusion coefficients from multi b-value MR experiments
      despite the airways being too small to be resolved by direct imaging. Herein a
      Bayesian approach is used for analyzing the uncertainties in the model parameter
      estimates. The approach allows evaluation of relative errors of the parameter
      estimates as functions of the "true" values of the parameters, the signal-to
      noise ratio, the maximum b-value and the total number of b-values used in the
      experiment. For a given set of the "true" diffusion parameters, the uncertainty
      in the estimated diffusion coefficients has a minimum as a function of maximum b
      value and total number of data points. Choosing the MR pulse sequence parameters
      corresponding to this minimum optimizes the diffusion MR experiment and gives the
      best possible estimates of the diffusion coefficients. The mathematical approach
      presented can be generalized for models containing arbitrary numbers of estimated
      parameters.

PMID- 17030133
TI  - The influence of nitrogen-15 proton-driven spin diffusion on the measurement of
      nitrogen-15 longitudinal relaxation times.
AB  - The effect of nitrogen-15 proton-driven spin diffusion on quantitative (15)N T(1)
      measurements in solid proteins is investigated, and the impact on the measurement
      of dynamic parameters is assessed. A simple model of exchange between neighboring
      nitrogens is used to reproduce the evolution of (15)N spin systems whose
      longitudinal relaxation rates and exchange rates are compatible with experimental
      measurements. We show that the induced error in the measured T(1) and its effect
      on the determination of dynamics parameters is likely to be less than the current
      experimental error. The use of deuterated protein samples is shown to have a
      small but sometimes visible effect, and may also considerably slow down or even
      suppress the exchange of magnetization due to spin diffusion.

PMID- 17030134
TI  - Application of the independent molecule model to elucidate the dynamics of
      structure I methane hydrate.
AB  - Raman spectroscopy has exhibited the C-H stretch (A1 mode) frequency nu1 of
      hydrated methanes at 2915 cm(-1) for the 5(12) cage and 2905 cm(-1) for the
      5(12)6(2) cage. These values are lower than the frequency of 2916.5 cm(-1) in
      gaseous methane. In this paper, we theoretically examine the Raman spectra
      observed in methane hydrate by normal mode analysis using the independent
      molecule model. By a breakdown of the symmetry, the four frequencies in modes A1,
      E, T2 and T2 observed in gaseous methane are separated into nine frequencies in
      the hydrate. It is necessary to consider the anharmonic potential energy within
      methane and hydrogen bonding between methane hydrogen and water oxygen in order
      to get a result in qualitative agreement with experiment. The frequency in the
      5(12)6(2) cage is shifted downward in comparison to the one in 5(12), and the
      frequencies in the both cages are also shifted downward compared with the
      frequencies in gas. Calculations are also reported for the isotopic methane (CD4,
      13CH4) hydrates.

PMID- 17030135
TI  - Influence of physical preconditioning on the responsiveness of rat pulmonary
      artery after pulmonary ischemia/reperfusion.
AB  - The aim of this work was to evaluate the effect of physical preconditioning in
      the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion
      (IR). Wistar rats were divided into three groups: Sedentary sham-operated
      (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained
      submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in
      sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary
      IR was performed by occluding for 90 min and reperfusing for 120 min. After that,
      pulmonary arteries were isolated and concentration-response curves to
      acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine
      and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses
      (E(max)) were modified for ACh and HIST in all groups. On the other hand, the
      potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared
      to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic
      receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR:
      6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the
      U46619 in all groups. In conclusion, the present study shows that exercise
      training has no protective actions in the local blood vessel where the IR process
      takes place.

PMID- 17030136
TI  - Maternal diet influences gene expression in intestine of offspring in chicken
      (Gallus gallus).
AB  - The diet of the mother during pregnancy influences the onset of different
      diseases and health-related traits in the offspring. We investigated the
      influence of the mother hen diet on the intestinal gene expression pattern in the
      offspring. Hens received for 11 weeks either a commercial feed or a commercial
      feed supplemented with vitamins and minerals. The offspring of the two groups
      showed no changes in growth rate or feed conversion. Of this offspring, gene
      expression patterns in the intestine were measured at 3 and 14 days of age with
      an intestinal cDNA-microarray. Between the two groups, 11 genes were found to be
      differentially expressed both at 3 and 14 days of age. Thus, these genes were
      differently regulated when the intestine is developing as well as when the
      intestine is more mature. Genes that are differentially expressed at day 3 and/or
      day 14 affect intestinal turnover, proliferation and development, metabolism and
      feed absorption. To confirm that differences in gene expression are related to
      intestinal development, we investigated intestinal proliferation. This indeed
      also showed differences in proliferation between the two groups at day 3 and day
      14 of age. The gene expression and proliferation results indicate that feed of
      the hens influences the functionality of intestine of the offspring at day 3 and
      14 of age.

PMID- 17030137
TI  - Effect of sudden salinity change on Penaeus latisulcatus Kishinouye
      osmoregulation, ionoregulation and condition in inland saline water and potassium
      fortified inland saline water.
AB  - Two trials were conducted to determine the effect of sudden decrease in salinity
      of raw and potassium-fortified inland saline water on western king prawn Penaeus
      latisulcatus osmoregulation, ionoregulation and condition. Prawns were subjected
      to salinity decrease over 1 h from 32 to 25 ppt in the first trial and from 27 to
      20 ppt in the second trial in three water types: inland saline water with
      potassium fortified to 100% and 80% of the marine water concentration (IS100,
      IS80), and raw inland saline water (ISW). In the first trial condition and
      ingestion rate were monitored over 19 days following salinity change. In the
      second trial condition, haemolymph osmo- and iono-regulation were recorded over
      48 h following salinity change. In the first trial, 100% mortality was observed
      in ISW by day 13, with final survival 94% in IS80 and 100% in IS100. Tail muscle
      moisture content increased significantly (P < 0.05) over time in both trials and
      in all water types, suggesting loss of energy reserves. In the second trial,
      serum osmolality, sodium concentration and osmoregulatory capacity decreased
      following salinity change, stabilising by 24 h in IS100 and IS80 but continuing
      to decrease till 48 h in ISW, suggesting partial breakdown of osmoregulatory
      function in the potassium-deficient medium. Prawns were stronger regulators of
      divalent than monovalent cations. These trials demonstrate that potassium
      deficient inland saline water requires fortification with potassium to allow
      prawn survival and efficient osmoregulation.

PMID- 17030138
TI  - Muscle delta13C change in Nile tilapia (Oreochromis niloticus) fingerlings fed on
      C3-or C4-cycle plants grain-based diets.
AB  - The effects of grain-based diets from C3 or C4-cycle plants on muscle delta(13)C
      change process in Nile tilapia (Oreochromis niloticus) fingerlings were
      investigated. Two groups of sex reversal males Nile tilapia fingerlings were fed
      with isoproteic (32.0% DP) and isocaloric (3200 kcal DE/kg) diets, differing from
      each other by their delta(13)C. Muscle samples were collected and the carbon
      isotopic composition was measured. For C4 diet, the formula for the muscle
      delta(13)C change related to the intake time of a new diet was delta(13)C=-14.88
      9.21e(-0.0209t) and the half-life (T) of the muscle carbon was 33.2 days. For C3
      diet, the formula was delta(13)C=-25.43+8.59e(-0.0533t) with T=13 days. The C3
      diet was considered more appropriate based on its palatability and consequent
      larger food intake than the C4 diet, resulting in an increased muscle delta(13)C
      change rate. However, for future studies, would be necessary to mix both the C3
      and C4 feedstuffs to formulate diets nutritionally appropriated, with contrasting
      stable isotopes signatures. Tissue delta(13)C change rate is therefore indicated
      as a promising tool to better understand the biotic and abiotic factors that
      influence nutrients utilization from the diet and animal growth.

PMID- 17030139
TI  - Left ventricular myocardal activation under ventricular paced beats in chickens
      Gallus gallus domesticus.
AB  - The aim of the study was to advance our knowledge regarding the activation
      process of the ventricular myocardium in birds in which Purkinje fibres penetrate
      into the ventricular wall to reach the epicardium. A depolarization pattern of
      the left ventricular free wall was studied in chickens (Gallus gallus) during
      ventricular paced beats. Duration of the activation process of the left
      ventricular free wall is significantly increased during ventricular ectopic
      excitation as compared with sinus rhythm. Its lowest increase occurs during
      subendocardial pacing of the middle part of the left ventricle, but its greatest
      increase is observed during subepicardial pacing of the left ventricular base.
      Multifocality and mosaicity of depolarization of the left ventricular free wall
      myocardium in chicken are expressed in a considerably less degree during
      ventricular paced beats in comparison with sinus rhythm. During ventricular paced
      beats, excitation of the left ventricular free wall is mostly due to the
      successive spreading of the depolarization wave from pacing sites.

PMID- 17030140
TI  - Effects of GH on immune and endocrine responses of channel catfish challenged
      with Edwardsiella ictaluri.
AB  - The effects of GH on immune and endocrine responses to channel catfish challenged
      with the bacterium Edwardsiella ictaluri were examined. Catfish (11.7+/-1.0 g)
      treated with recombinant bovine growth hormone (rbGH) and challenged with E.
      ictaluri experienced similar mortality as control-exposed fish. Plasma activity
      of lysozyme was higher (P<0.01) in rbGH-exposed fish. Compared to day 0 controls
      (non-exposed fish), IGF-I levels decreased (P<0.05) in challenged fish while
      levels were similar (P>0.10) between treatments. Abundance of GH receptor (GHR)
      mRNA tended to decrease (P=0.055) in liver of challenged fish while toll like
      receptor 5 (TLR5) mRNA increased (P<0.05) in liver compared to d 0 controls. An
      increase in lysozyme may suggest GH enhances a nonspecific immune response. A
      decrease in GHR mRNA and plasma IGF-I suggests a downregulation of the
      somatotropic axis in response to disease. The increase in TLR5 mRNA suggests that
      TLR5 may play a role in host response to bacterial challenge. While exogenous
      rbGH may play a stimulatory role to increase lysozyme levels, there was no
      apparent effect of rbGH on mortality to E. ictaluri.

PMID- 17030141
TI  - Structural characterization of the lipovitellin from the shrimp Macrobrachium
      borellii.
AB  - In oviparous species, proteins and lipids are found in the vitellus forming
      lipoproteins called lipovitellins. They are an important energy source for
      embryos development and larvae growth and survival. We have previously isolated
      and partially characterized the sole egg cytosolic lipovitellin from the
      freshwater shrimp Macrobrachium borellii. It is a native protein of 440 kDa,
      composed of two subunits of 94 and 112 kDa. In the present work we studied size,
      shape and structure of M. borellii lipovitellin using electron microscopy,
      crosslinking reagents, MALDI-TOF, circular dichroism, fluorescence and partial
      proteolysis. The results showed that lipovitellin has a quasi spherical
      morphology with an estimated diameter of 18.5+/-3.5 nm. It appears to be composed
      of two subunits of 94 kDa, and one of 112 kDa. The larger subunit is more
      susceptible to trypsinolysis, indicating that it is less compactly folded and/or
      more exposed to the aqueous medium than the 94 kDa subunits. The hetero-trimer is
      held together by non-covalent interactions. Peptide mass fingerprinting by MALDI
      TOF, produced 42 polypeptides matching to a vitellogenin of a related species
      (Macrobrachium rosenbergii). Circular dichroism indicated that this protein
      contains 35.7% alpha-helix, 16.6% beta-sheet and 20% turns. Tryptophan
      fluorescence emission, at a maximum of 334 nm, indicated that the environment
      polarity of these aromatic residues is similar to that of other crustacean
      lipoproteins.

PMID- 17030142
TI  - A combined study of heat and mass transfer in an infant incubator with an
      overhead screen.
AB  - The main objective of this study is to investigate the major physical processes
      taking place inside an infant incubator, before and after modifications have been
      made to its interior chamber. The modification involves the addition of an
      overhead screen to decrease radiation heat losses from the infant placed inside
      the incubator. The present study investigates the effect of these modifications
      on the convective heat flux from the infant's body to the surrounding environment
      inside the incubator. A combined analysis of airflow and heat transfer due to
      conduction, convection, radiation and evaporation has been performed, in order to
      calculate the temperature and velocity fields inside the incubator before and
      after the design modification. Due to the geometrical complexity of the model,
      computer-aided design (CAD) applications were used to generate a computer-based
      model. All numerical calculations have been performed using the commercial
      computational fluid dynamics (CFD) package FLUENT, together with in-house
      routines used for managing purposes and user-defined functions (UDFs) which
      extend the basic solver capabilities. Numerical calculations have been performed
      for three different air inlet temperatures: 32, 34 and 36 degrees C. The study
      shows a decrease of the radiative and convective heat losses when the overhead
      screen is present. The results obtained were numerically verified as well as
      compared with results available in the literature from investigations of dry heat
      losses from infant manikins.

PMID- 17030144
TI  - Engineering novel traits in plants through RNA interference.
AB  - RNA interference (RNAi) is a homology-dependent gene silencing technology that
      involves double-stranded RNA directed against a target gene or its promoter
      region. Using hairpin constructs, double-stranded RNA can be expressed in plants
      relatively easily, enabling this technology to be applied to a wide range of
      species to silence the expression of both specific endogenous genes and genes of
      invading pathogens. RNAi has also been used to engineer metabolic pathways to
      overproduce secondary products with health, yield or environmental benefits. The
      application of tissue-specific or inducible gene silencing, with the use of
      appropriate promoters, and the ability to silence several genes simultaneously
      should enhance our ability to create novel traits in plants.

PMID- 17030145
TI  - Plant nitric oxide synthase: a never-ending story?

PMID- 17030146
TI  - Receptor protein kinases--pattern recognition receptors in plant immunity.
AB  - Plant innate immunity is activated either upon perception of pathogen-associated
      molecular patterns (PAMPs) by pattern recognition receptors (PRRs) or upon
      resistance (R) protein-mediated recognition of pathogen race-specific effector
      molecules. Although many plant R proteins have been identified, there is only
      limited knowledge about plant PRRs. Recently, Cyril Zipfel et al. identified a
      second Arabidopsis leucine-rich repeat receptor protein kinase implicated in PAMP
      perception, which suggests that several members of this large protein family
      function as pattern recognition receptors.

PMID- 17030147
TI  - Auxin and cell polarity: the emergence of AXR4.
AB  - Polar localization of the Arabidopsis auxin influx facilitator protein AUX1 in
      certain cell types is essential for normal root gravitropism and lateral root
      formation. Sunethra Dharmasiri and colleagues recently reported that this polar
      localization requires the activity of the AXR4 gene. The sequence of the AXR4
      gene suggests that novel mechanisms could be important for targeting certain
      proteins to specific cellular locations.

PMID- 17030148
TI  - Nickel(II) complexes of biologically active glutathione: spectroscopic, kinetics
      of thermal decomposition and XRPD studies.
AB  - Nickel(II) complexes of reduced glutathione (GSH) of general composition
      Na[Ni(L)(X)]H(2)O, where H(2)L=GSH; X=NO(3)(-), SCN(-), CH(3)CO(2)(-), Cl(-) have
      been synthesized and characterized by elemental analysis, infrared spectra,
      electronic spectra, magnetic susceptibility measurements, thermal and X-ray
      powder diffraction studies. Infrared spectra indicate deprotonation and
      coordination of cysteinyl sulphur and carboxylate oxygen of glycine residue with
      nickel ions. It indicates the presence of water molecule in all the complexes
      which has been supported by TG/DTA. The thermal behavior of complexes shows that
      water molecule is removed in first step-followed removal of anions and then
      decomposition of the ligand molecule in subsequent steps. General mechanisms
      describing the decomposition of the solid complexes are suggested. Kinetic and
      thermodynamic parameters were computed from the thermal decomposition data. The
      room temperature magnetic moment values for all the complexes lie in the range of
      2.2-2.4BM, indicating departure from spin only values due to second order Zeeman
      effect. The electronic spectra indicate planar coordination geometry for all the
      complexes. Crystal data for Na[Ni(L)(CH(3)CO(2)(-))]H(2)O: tetragonal, space
      group P4/m, a=8.2004A, b=8.2004A, c=16.0226A, V=1077.47A(3), Z=2. Crystal data
      for Na[Ni(L)(Cl(-))]H(2)O: cubic, space group Pm3, a=16.1055A, b=16.1055A,
      c=16.1055A, V=4178.38A(3), Z=6. Crystal data for Na[Ni(L)(NO(3)(-))]H(2)O:
      tetragonal, space group P4/m, a=7.2121A, b=7.2121A, c=12.0200A, V=625.22A(3),
      Z=2.

PMID- 17030149
TI  - Spectral, electrical conductivity and biological activity properties of some new
      azopyrimidine derivatives and their complexes.
AB  - The electronic absorption spectra of 5-(o-substituted phenylazo)-6-amino-2
      thiouracils and 6-(o-substituted phenylazo)-5-aminouracils containing different
      substituents are studied at different pH's. The dissociation constants are
      evaluated and discussed. Phenomenon of tautomerism is more supported by (1)H NMR
      and (13)C NMR spectra. The electrical conductivity of some ligands and their
      Co(II), Ni(II) and Cu(II) complexes in the temperature range 293-150K favoured
      their semiconducting properties where the metal ion forms a bridge to facilitate
      the flow of the current. The biological activity of some ligands and their
      complexes are tested against a number of Gram-positive and Gram-negative
      bacteria. The results showed that some of the compounds have a well considerable
      activity against some of the organisms.

PMID- 17030150
TI  - Transfusion medicine in Norway: new problems and new opportunities.
AB  - During 2005 Norwegian Transfusion Medicine has faced some new problems, sought
      new solutions and gained strength. Interactions with the public and the health
      authorities have been important issues for consideration, which are discussed
      below.

PMID- 17030151
TI  - Immunological and biochemical responses in Mya arenaria (Mollusca Bivalvia)
      exposed in vivo to estradiol-17beta.
AB  - Soft-shell clams Mya arenaria were injected with 10, 20 or 40 nmol of estradiol
      17beta (E2). We observed a significant inhibiting effect of E2 on phagocytic
      activity of hemocytes from clams exposed to 10 and 20 nmol. A dose-response
      increase of the glycogen phosphorylase in the gonad tended to show a
      remobilisation of glycogen reserves involved in vitellogenesis although the
      exposure time must have been too short to observe a decrease in glycogen reserves
      or an increase in RNA concentration. Both results corroborate those of other
      studies about estrogen involvement in controlling immune capacity and energy
      metabolism related to vitellogenesis in bivalves. We can assume that immune
      parameters should now be taken into consideration in assessing endocrine
      disruption in bivalves. Nevertheless further studies are needed to understand the
      controlling pathways of E2 with a special regard on its interactions with other
      effectors involved in bivalve immunity and reproduction as well.

PMID- 17030152
TI  - The application of genomic and proteomic technologies in predictive, preventive
      and personalized medicine.
AB  - The long asymptomatic period before the onset of chronic diseases offers good
      opportunities for disease prevention. Indeed, many chronic diseases may be
      preventable by avoiding those factors that trigger the disease process (primary
      prevention) or by use of therapy that modulates the disease process before the
      onset of clinical symptoms (secondary prevention). Accurate prediction is vital
      for disease prevention so that therapy can be given to those individuals who are
      most likely to develop the disease. The utility of predictive markers is
      dependent on three parameters, which must be carefully assessed: sensitivity,
      specificity and positive predictive value. Specificity is important if a
      biomarker is to be used to identify individuals either for counseling or for
      preventive therapy. However, a reciprocal relationship exists between sensitivity
      and specificity. Thus, successful biomarkers will be highly specific without
      sacrificing sensitivity. Unfortunately, biomarkers with ideal specificity and
      sensitivity are difficult to find for many diseases. One potential solution is to
      use the combinatorial power of a large number of biomarkers, each of which alone
      may not offer satisfactory specificity and sensitivity. Recent technological
      advances in genetics, genomics, proteomics, and bioinformatics offer a great
      opportunity for biomarker discovery. The newly identified biomarkers have the
      potential to bring increased accuracy in disease diagnosis and classification, as
      well as therapeutic monitoring. In this review, we will use type 1 diabetes (T1D)
      as an example, when appropriate, to discuss pertinent issues related to high
      throughput biomarker discovery.

PMID- 17030153
TI  - Screening for Auditory Impairment-Which Hearing Assessment Test (SAI-WHAT): RCT
      design and baseline characteristics.
AB  - BACKGROUND: Effective screening programs should not merely detect presence of
      disease, but also lead to long-term benefit. We describe the rationale and design
      of the first randomized clinical trial to study the long-term effects of routine
      screening for hearing loss. We also describe the baseline characteristics of the
      randomized cohort. METHODS: We randomized 2305 veterans age 50 years or older to
      a control arm without screening, or to screening with: physiologic testing
      (AudioScope), a self-administered questionnaire (Hearing Handicap Inventory for
      the Elderly-Screening version [HHIE-S]), or both tests. The primary outcome
      measure will be hearing aid use one year after screening. We will also study a
      number of secondary outcomes, including appointments made with and visits to an
      audiologist, cases of aidable hearing loss, hearing aids dispensed, self-rated
      communication ability, and hearing-related quality of life. RESULTS: Baseline
      demographic and health status measures were evenly distributed across the
      screening arms. The percentage of patients who screened positive for hearing loss
      was 18.6%, 59.2%, and 63.6% for the AudioScope, HHIE-S, and combined screening
      arms, respectively. IMPLICATIONS: Long-term results are needed to gain insight
      into whether the AudioScope is associated with high rates of false negative
      screening, the HHIE-S is associated with high rates of false positive screening,
      or a combination of both. Identifying the best screening program will depend on
      determining which strategy leads to successful hearing aid use.

PMID- 17030154
TI  - Value of recruitment strategies used in a primary care practice-based trial.
AB  - PURPOSE: "Physicians-recruiting-physicians" is the preferred recruitment approach
      for practice-based research. However, yields are variable; and the approach can
      be costly and lead to biased, unrepresentative samples. We sought to explore the
      potential efficiency of alternative methods. METHODS: We conducted a
      retrospective analysis of the yield and cost of 10 recruitment strategies used to
      recruit primary care practices to a randomized trial to improve cardiovascular
      disease risk factor management. We measured response and recruitment yields and
      the resources used to estimate the value of each strategy. Providers at recruited
      practices were surveyed about motivation for participation. RESULTS: Response to
      6 opt-in marketing strategies was 0.40% (53/13290), ranging from 0% to 2.86% by
      strategy; 33.96% (18/53) of responders were recruited to the study. Of those
      recruited from opt-out strategies, 8.68% joined the study, ranging from 5.35% to
      41.67% per strategy. A strategy that combined both opt-in and opt-out approaches
      resulted in a 51.14% (90/176) response and a 10.80% (19/90) recruitment rate.
      Cost of recruitment was $613 per recruited practice. Recruitment approaches based
      on in-person meetings (41.67%), previous relationships (33.33%), and borrowing an
      Area Health Education Center's established networks (10.80%), yielded the most
      recruited practices per effort and were most cost efficient. Individual providers
      who chose to participate were motivated by interest in improving their clinical
      practice (80.5%); contributing to CVD primary prevention (54.4%); and
      invigorating their practice with new ideas (42.1%). CONCLUSIONS: This analysis
      provides suggestions for future recruitment efforts and research. Translational
      studies with limited funds could consider multi-modal recruitment approaches
      including in-person presentations to practice groups and exploitation of previous
      relationships, which require the providers to opt-out, and interactive opt-in
      approaches which rely on borrowed networks. These approaches can be supplemented
      with non-relationship-based opt-out strategies such as cold calls strategically
      targeted to underrepresented provider groups.

PMID- 17030156
TI  - Evaluation of the influence of protein precipitation prior to on-line SPE-LC
      API/MS procedures using multivariate data analysis.
AB  - Matrix effects on mass spectrometry (MS) response were investigated with three
      atmospheric pressure ionization (API) sources after on-line solid-phase
      extraction (SPE) of human plasma. On-line SPE was evaluated with one restricted
      access material (RAM), two large particle supports (LPS) and one monolith. A
      sample protein precipitation (PP) with acetonitrile (2:1) and a direct injection
      were tested. Principal component analysis (PCA) was performed to simplify data
      presentation and interpretation. Protein precipitation was found to be mandatory
      for reducing signal modification. Regarding sensitivity towards matrix effects
      after PP, atmospheric pressure photoionization (APPI) was globally the least
      sensitive ionization mode while electrospray ionization ESI was the most
      sensitive.

PMID- 17030155
TI  - Rationale and design of the AdRem study: evaluating the effects of blood pressure
      lowering and intensive glucose control on vascular retinal disorders in patients
      with type 2 diabetes mellitus.
AB  - The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study
      evaluating the effects of target driven intensive glucose control and placebo
      controlled blood pressure lowering on retinal vascular changes. AdRem is a sub
      study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2
      factorial randomized controlled trial with an ACE inhibitor-diuretic combination
      (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type
      2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal
      photographs of both eyes. These are taken within 3 months after randomization in
      ADVANCE (baseline), at the biennial and at the final visit. The primary outcome
      is progression of two or more steps in ETDRS classification. Secondary outcomes
      include progression of retinal vascular lesions and distortion of retinal
      vascular geometry. Retinal photographs are made on film and digitized at a
      central laboratory. The AdRem study uses fully digitized quality control and
      grading. Between August 2002 and January 2004 1978 patients were included in the
      AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the
      strict AdRem quality requirements. Publication of the results is expected in
      early 2008. The AdRem study is designed to provide reliable evidence on the
      effects of intensive glucose control and blood pressure lowering on both diabetic
      retinopathy and abnormalities of retinal vasculature in patients with type 2
      diabetes mellitus.

PMID- 17030157
TI  - Validated GC-MS analysis for the determination of residual fentanyl in applied
      Durogesic reservoir and Durogesic D-Trans matrix transdermal fentanyl patches.
AB  - The method development and validation characteristics are described of a simple
      gas chromatographic-mass spectrometric (GC-MS) analytical procedure to determine
      residual fentanyl in used Durogesic reservoir patches and Durogesic D-Trans
      matrix technology based systems to estimate the actual rate of transdermal
      fentanyl delivered in individual patients. The sample preparation protocol
      constituting a saline based extraction of sets of new patches of each nominal
      dose available, resulted in fentanyl extraction recoveries to increase steadily
      as a function of increasing extraction time. For the reservoir type transdermal
      therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h)
      ranged from approximately 60% (100-microg/h TTS) to 95% (25-microg/h TTS),
      whereas for the matrix type system considerable lower recoveries were
      demonstrated for the highest nominal dose rates (35%-52%), while reaching 90% for
      the 25-microg/h system. For the latter type of fentanyl TTS, an optimized
      methanol based extraction protocol yielded virtually quantitative fentanyl
      recoveries for each matrix patch nominal dose level at substantially shorter
      extraction periods (15 min). The GC-MS analytical method using selected ion
      monitoring (SIM) and deuterated fentanyl as internal standard was shown to be
      adequately selective with regard to the presence of other compounds in the
      Durogesic patches. It was further demonstrated that the developed analytical
      protocols provided highly reproducible and accurate estimates of the initial
      fentanyl content of each patch type at all available nominal doses, with
      coefficients of variation and relative errors generally below 10%. These
      advantageous assay validation characteristics can be further transposed to the
      application of residual fentanyl level estimates in used patches, provided that
      with each batch of samples also a set of new TTSs with equal dose is assayed to
      perfectly mimic extraction phenomena. Finally, the presented GC-MS analytical
      protocol was successfully applied for the determination of residual fentanyl in a
      subset of 57 reservoir type patches obtained from four palliative patients.

PMID- 17030158
TI  - Protein A chromatography for antibody purification.
AB  - Staphylococcal protein A (SPA) is one of the first discovered immunoglobulin
      binding molecules and has been extensively studied during the past decades. Due
      to its affinity to immunoglobulins, SPA has found widespread use as a tool in the
      detection and purification of antibodies and the molecule has been further
      developed to one of the most employed affinity purification systems.
      Interestingly, a minimized SPA derivative has been constructed and a domain
      originating from SPA has been improved to withstand the harsh environment
      employed in industrial purifications. This review will focus on the development
      of different affinity molecules and matrices for usage in antibody purification.

PMID- 17030165
TI  - Obesity epidemic in need of answers.

PMID- 17030159
TI  - How tough is bone? Application of elastic-plastic fracture mechanics to bone.
AB  - Bone, with a hierarchical structure that spans from the nano-scale to the macro
      scale and a composite design composed of nano-sized mineral crystals embedded in
      an organic matrix, has been shown to have several toughening mechanisms that
      increases its toughness. These mechanisms can stop, slow, or deflect crack
      propagation and cause bone to have a moderate amount of apparent plastic
      deformation before fracture. In addition, bone contains a high volumetric
      percentage of organics and water that makes it behave nonlinearly before
      fracture. Many researchers used strength or critical stress intensity factor
      (fracture toughness) to characterize the mechanical property of bone. However,
      these parameters do not account for the energy spent in plastic deformation
      before bone fracture. To accurately describe the mechanical characteristics of
      bone, we applied elastic-plastic fracture mechanics to study bone's fracture
      toughness. The J integral, a parameter that estimates both the energies consumed
      in the elastic and plastic deformations, was used to quantify the total energy
      spent before bone fracture. Twenty cortical bone specimens were cut from the mid
      diaphysis of bovine femurs. Ten of them were prepared to undergo transverse
      fracture and the other 10 were prepared to undergo longitudinal fracture. The
      specimens were prepared following the apparatus suggested in ASTM E1820 and
      tested in distilled water at 37 degrees C. The average J integral of the
      transverse-fractured specimens was found to be 6.6 kPa m, which is 187% greater
      than that of longitudinal-fractured specimens (2.3 kPa m). The energy spent in
      the plastic deformation of the longitudinal-fractured and transverse-fractured
      bovine specimens was found to be 3.6-4.1 times the energy spent in the elastic
      deformation. This study shows that the toughness of bone estimated using the J
      integral is much greater than the toughness measured using the critical stress
      intensity factor. We suggest that the J integral method is a better technique in
      estimating the toughness of bone.

PMID- 17030166
TI  - Diagnostic colonoscopy: the end is coming.

PMID- 17030167
TI  - Clinical challenges and images in GI. Portal cavernoma-associated cholangiopathy.

PMID- 17030168
TI  - Clinical challenges and images in GI. Pill esophagitis.

PMID- 17030169
TI  - Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase
      Ib, placebo-controlled, randomized study.
AB  - BACKGROUND & AIMS: VX-950 specifically inhibits the NS3.4A protease of hepatitis
      C and has antiviral activity in vitro. This phase I, placebo-controlled, double
      blind study evaluated the antiviral activity, pharmacokinetics, and safety of VX
      950 in patients with chronic hepatitis C (CHC). METHODS: Thirty-four patients
      with genotype 1 CHC were randomized to receive placebo or VX-950 at doses of 450
      mg or 750 mg every 8 hours or 1250 mg every 12 hours for 14 days. Of the 34
      participants, 27 (79%) had failed prior treatment. Patients were monitored for
      safety and tolerability of VX-950. Plasma VX-950 concentrations and HCV RNA
      levels were measured. RESULTS: VX-950 was well tolerated and had substantial
      antiviral effects: viral loads dropped > or =2 log(10) in all 28 patients treated
      with VX-950 and > or =3 log(10) in 26 (93%) of the 28 patients. In the 750-mg
      dose group, which had the highest trough plasma drug concentrations, the median
      reduction of HCV RNA was 4.4 log(10) after 14 days. In the 450-mg and 1250-mg
      groups, the maximal effect was seen between days 3 and 7 of dosing, and median
      HCV RNA increased between days 7 and 14; median reductions at day 14 were 2.4
      log(10) and 2.2 log(10), respectively. Median alanine aminotransferase levels
      decreased during dosing in all VX-950 groups. CONCLUSIONS: VX-950 was well
      tolerated and demonstrated substantial antiviral activity. Some patients had
      viral breakthrough during dosing, related to selection of variants with decreased
      sensitivity to VX-950. The results support further studies of VX-950 in patients
      with CHC.

PMID- 17030170
TI  - Relationship of abdominal bloating to distention in irritable bowel syndrome and
      effect of bowel habit.
AB  - BACKGROUND & AIMS: The relationship between the sensation of bloating, often
      ranked as the most bothersome symptom by patients with irritable bowel syndrome
      (IBS), and actual distention manifest as an increase in abdominal girth is
      controversial. Investigation of this problem has been hampered by the lack of a
      reliable ambulatory technique to measure abdominal girth. The aim of this study
      was to use the technique of abdominal inductance plethysmography to compare
      diurnal variation in girth in IBS patients and healthy volunteers, relating these
      changes to the sensation of bloating. METHODS: Abdominal girth was recorded for
      24 hours in 20 IBS-constipation (age, 18-73 y), 20 IBS-diarrhea (age, 25-62 y)
      and 10 IBS-alternating (age, 21-59 y) female patients meeting Rome II criteria
      and 20 healthy female controls (age, 18-67 y). All subjects pursued normal daily
      activities, recording their symptoms of bloating and pain together with bowel
      habit. RESULTS: All patients with IBS, irrespective of bowel habit, reported
      significantly greater bloating than controls (P < .0001). Forty-eight percent of
      patients also showed distention beyond the 90% control range, with this being
      most prominent in IBS-constipation. Bloating correlated strongly only with
      distention in IBS-constipation (r > or = 0.48; P < or = .02). Neither bloating
      nor distention in IBS was related to body mass index, age, parity, or psychologic
      status. CONCLUSIONS: Abdominal distention is a clearly definable phenomenon in
      IBS that can reach 12 cm. However, it only occurs in half of patients reporting
      bloating, and the 2 only correlate in IBS-constipation. Bloating and distention
      may differ pathophysiologically and this appears to be reflected in the bowel
      habit subtype.

PMID- 17030171
TI  - Risk stratification for colon neoplasia: screening strategies using colonoscopy
      and computerized tomographic colonography.
AB  - BACKGROUND & AIMS: We developed a risk index to identify low-risk patients who
      may be screened for colorectal cancer with computerized tomographic colonography
      (CTC) instead of colonoscopy. METHODS: Asymptomatic persons aged 50 years or
      older who had undergone screening colonoscopy were randomized retrospectively to
      derivation (n = 1512) and validation (n = 1493) subgroups. We developed a risk
      index (based on age, sex, and family history) from the derivation group. The
      expected results of 3 screening strategies--universal colonoscopy, universal CTC,
      and a stratified strategy of colonoscopy for high-risk and CTC for low-risk
      patients--were then compared. Outcomes for the 3 strategies were extrapolated
      from the known colonic findings in each patient, using sensitivity/specificity
      values for CTC from the medical literature. Results were validated in the
      validation subgroup. RESULTS: In the derivation subgroup, universal colonoscopy
      detected 94% of advanced neoplasia and universal CTC detected only 70% and
      resulted in the largest total number of procedures and number of patients
      undergoing both procedures. The stratified strategy detected 92% of advanced
      neoplasia, requiring colonoscopy in 68% and CTC in 36% of patients, with only 4%
      having to undergo both procedures. In the validation subgroup, universal
      colonoscopy detected 94% and universal CTC detected 71% of advanced neoplasia,
      whereas the stratified strategy detected 89%, requiring colonoscopy in 64% and
      CTC in 40%. Unlike universal CTC, the stratified strategy was independent of
      assumptions for CTC sensitivity, specificity, and threshold for colonoscopy.
      CONCLUSIONS: The stratified strategy based on our risk index may optimize the
      yield of colonoscopic resources and reduce the number of patients undergoing
      colonoscopy.

PMID- 17030172
TI  - Increased serum levels of complement C3a anaphylatoxin indicate the presence of
      colorectal tumors.
AB  - BACKGROUND & AIMS: Late diagnosis of colorectal carcinoma results in a
      significant reduction of average survival times. Yet despite screening programs,
      about 70% of tumors are detected at advanced stages (International Union Against
      Cancer stages III/IV). We explored whether detection of malignant disease would
      be possible through identification of tumor-specific protein biomarkers in serum
      samples. METHODS: A discovery set of sera from patients with colorectal
      malignancy (n = 58) and healthy control individuals (n = 32) were screened for
      potential differences using surface-enhanced laser desorption/ionization time-of
      flight mass spectrometry. Candidate proteins were identified and their expression
      levels were validated in independent sample sets using a specific immunoassay
      (enzyme-linked immunosorbent assay). RESULTS: By using class comparison and
      custom-developed algorithms we identified several m/z values that were expressed
      differentially between the malignant samples and the healthy controls of the
      discovery set. Characterization of the most prominent m/z values revealed a
      member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a
      desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of
      complement C3a-desArg predicted the presence of colorectal malignancy in a
      blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of
      96.2%. Increased serum levels were also detected in 86.1% of independently
      collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6%
      were classified as normal. CONCLUSIONS: Complement C3a-desArg is present at
      significantly higher levels in serum from patients with colorectal adenomas (P <
      .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that
      quantification of C3a-desArg levels could ameliorate existing screening tests for
      colorectal cancer.

PMID- 17030173
TI  - Relative contribution of genetic and nongenetic modifiers to intestinal
      obstruction in cystic fibrosis.
AB  - BACKGROUND & AIMS: Neonatal intestinal obstruction (meconium ileus [MI]) occurs
      in 15% of patients with cystic fibrosis (CF). Our aim was to determine the
      relative contribution of genetic and nongenetic modifiers to the development of
      this major complication of CF. METHODS: A total of 65 monozygous twin pairs, 23
      dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI
      status, significant covariates, and genome-wide linkage. RESULTS: Specific
      mutations in the CF transmembrane conductance regulator (CFTR), the gene
      responsible for CF, correlated with MI, indicating a role for CFTR genotype.
      Monozygous twins showed substantially greater concordance for MI than dizygous
      twins and siblings (P = 1 x 10(-5)), showing that modifier genes independent of
      CFTR contribute substantially to this trait. Regression analysis revealed that MI
      was correlated with distal intestinal obstruction syndrome (P = 8 x 10(-4)).
      Unlike MI, concordance analysis indicated that the risk for development of distal
      intestinal obstruction syndrome in CF patients is caused primarily by nongenetic
      factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0)
      for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or
      protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide
      analyses. These analyses did not support the existence of a major modifier gene
      on chromosome 19 in a region previously linked to MI. CONCLUSIONS: The CFTR gene
      along with 2 or more modifier genes are the major determinants of intestinal
      obstruction in newborn CF patients, whereas intestinal obstruction in older CF
      patients is caused primarily by nongenetic factors.

PMID- 17030174
TI  - Effect of ribavirin in genotype 1 patients with hepatitis C responding to
      pegylated interferon alfa-2a plus ribavirin.
AB  - BACKGROUND & AIMS: Pegylated interferon alfa-ribavirin combination is the
      standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin
      enhances the rate of sustained hepatitis C virus (HCV) eradication remain
      unknown. We aimed to investigate the role of ribavirin in HCV clearance during
      therapy and to evaluate the consequences of ribavirin discontinuation in patients
      infected with genotype 1 hepatitis C who cleared HCV RNA at week 24. METHODS: A
      total of 516 patients were treated with pegylated interferon alfa-2a, 180
      microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week
      24. They were randomized to continue with the combination or receive pegylated
      interferon alone. RESULTS: Responders at week 24 who stopped ribavirin had a
      significantly higher rate of breakthroughs during, and relapses after, therapy
      (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect
      profile and quality of life tended to improve. Multiple logistic regression
      analysis in the pegylated interferon alfa monotherapy group allowed
      identification of responders at week 24 who could stop ribavirin without losing
      their chance of a sustained virologic response, based on baseline viral load and
      age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is
      undetectable at week 2. CONCLUSIONS: We made 3 conclusions from this study.
      First, ribavirin primarily acts by sustaining the virologic response to pegylated
      interferon alfa; second, ribavirin must be administered for the full treatment
      duration in most genotype 1-infected patients who respond; third, baseline
      parameters may help identify patients who could discontinue ribavirin or reduce
      the dose without losing their chance of success.

PMID- 17030175
TI  - Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with
      advanced cirrhosis and hemorrhage.
AB  - BACKGROUND & AIMS: Oral norfloxacin is the standard of therapy in the prophylaxis
      of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage.
      However, during the last years, the epidemiology of bacterial infections in
      cirrhosis has changed, with a higher incidence of infections caused by quinolone
      resistant bacteria. This randomized controlled trial was aimed to compare oral
      norfloxacin vs intravenous ceftriaxone in the prophylaxis of bacterial infection
      in cirrhotic patients with gastrointestinal bleeding. METHODS: One hundred eleven
      patients with advanced cirrhosis (at least 2 of the following: ascites, severe
      malnutrition, encephalopathy, or bilirubin >3 mg/dL) and gastrointestinal
      hemorrhage were randomly treated with oral norfloxacin (400 mg twice daily; n =
      57) or intravenous ceftriaxone (1 g/day; n = 54) for 7 days. The end point of the
      trial was the prevention of bacterial infections within 10 days after inclusion.
      RESULTS: Clinical data were comparable between groups. The probability of
      developing proved or possible infections, proved infections, and spontaneous
      bacteremia or spontaneous bacterial peritonitis was significantly higher in
      patients receiving norfloxacin (33% vs 11%, P = .003; 26% vs 11%, P = .03; and
      12% vs 2%, P = .03, respectively). The type of antibiotic used (norfloxacin),
      transfusion requirements at inclusion, and failure to control bleeding were
      independent predictors of infection. Seven gram-negative bacilli were isolated in
      the norfloxacin group, and 6 were quinolone resistant. Non-enterococcal
      streptococci were only isolated in the norfloxacin group. No difference in
      hospital mortality was observed between groups. CONCLUSIONS: Intravenous
      ceftriaxone is more effective than oral norfloxacin in the prophylaxis of
      bacterial infections in patients with advanced cirrhosis and hemorrhage.

PMID- 17030176
TI  - Utility of a new model to diagnose an alcohol basis for steatohepatitis.
AB  - BACKGROUND & AIMS: Distinguishing an alcohol basis from a nonalcoholic basis for
      the clinical and histologic spectrum of steatohepatitic liver disease is
      difficult because of unreliability of alcohol consumption history. Unfortunately,
      various biomarkers have had limited utility in distinguishing alcoholic liver
      disease (ALD) from nonalcoholic fatty liver disease (NAFLD). Thus, the aim of our
      study was to create and validate a model to diagnose ALD in patients with
      steatohepatitis. METHODS: A cross-sectional cohort study was performed at the
      Mayo Clinic, Rochester, Minnesota, to create a model using multivariable logistic
      regression analysis. This model was validated in 3 independent data sets
      comprising patients of varying severity of steatohepatitis spanning over 10
      years. RESULTS: Logistic regression identified mean corpuscular volume, aspartate
      aminotransferase (AST)/alanine aminotransferase (ALT) ratio, body mass index, and
      gender as the most important variables that separated patients with ALD from
      NAFLD. These variables were used to generate the ALD/NAFLD Index (ANI), with ANI
      of greater than zero incrementally favoring ALD and ANI of less than zero
      incrementally favoring a diagnosis of NAFLD, thus making ALD unlikely. ANI had a
      c-statistic of 0.989 in the derivation sample, and 0.974, 0.989, 0.767 in the 3
      validation samples. ANI performance characteristics were significantly better
      than several conventional and recently proposed biomarkers used to differentiate
      ALD from NAFLD, including the histopathologic marker protein tyrosine phosphatase
      1b, AST/ALT ratio, gamma-glutamyl transferase, and carbohydrate-deficient
      transferrin. CONCLUSIONS: ANI, derived from easily available objective variables,
      accurately differentiates ALD from NAFLD in hospitalized, ambulatory, and
      pretransplantation patients and compares favorably with other traditional and
      proposed biomarkers.

PMID- 17030177
TI  - Advanced cytologic techniques for the detection of malignant pancreatobiliary
      strictures.
AB  - BACKGROUND & AIMS: Two advanced cytologic techniques for detecting aneuploidy
      digital image analysis (DIA) and fluorescence in situ hybridization (FISH)-have
      recently been developed to help identify malignant pancreatobiliary strictures.
      The aim of this study was to assess the clinical utility of cytology, DIA, and
      FISH for the identification of malignant pancreatobiliary strictures. METHODS:
      Brush cytologic specimens from 233 consecutive patients undergoing endoscopic
      retrograde cholangiopancreatography for pancreatobiliary strictures were examined
      by all 3 (cytology, DIA, and FISH) techniques. Strictures were stratified as
      proximal (n = 33) or distal (n = 114) based on whether they occurred above or
      below the cystic duct, respectively. Strictures in patients with primary
      sclerosing cholangitis (n = 86) were analyzed separately. RESULTS: Despite the
      stratification, the performances of the tests were similar. Conventional cytology
      has a low sensitivity (4%-20%) but 100% specificity. Because of the high
      specificity for cytology, we assessed the performance of the other tests when
      conventional cytology was negative. In this clinical context, FISH had an
      increased sensitivity (35%-60%) when assessing for chromosomal gains (polysomy)
      while preserving the specificity of cytology. The sensitivity and specificity of
      DIA was intermediate as compared with routine cytology and FISH but was additive
      to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3.
      CONCLUSIONS: These findings suggest that FISH and DIA increase the sensitivity
      for the diagnosis of malignant pancreatobiliary tract strictures over that
      obtained by conventional cytology while maintaining an acceptable specificity.

PMID- 17030178
TI  - STAT3 activation regulates growth, inflammation, and vascularization in a mouse
      model of gastric tumorigenesis.
AB  - BACKGROUND & AIMS: The gp130(757F/F) mouse is a well-characterized and robust
      model of distal gastric tumorigenesis displaying many of the characteristics of
      human intestinal type gastric cancer. Key to the development of tumors in this
      model, and in many examples of human tumor development, is hyperactivation of the
      transcription factor STAT3. This study addressed the requirement for STAT3
      activation in tumor initiation and characterized some of the genes downstream of
      STAT3 required for tumor development. Furthermore, the interaction among STAT3,
      the microbial environment, and tumorigenesis was evaluated. METHODS: The role of
      STAT3 in gastric tumor development was assessed in detail in
      gp130(757F/Y757F):STAT3(+/-) mice displaying reduced STAT3 activity. Tumor size
      was quantified morphologically, and the effects on endocrine cell populations,
      neovascularization, and inflammatory cell infiltration as well as the outcome of
      STAT3 activation on transcription of a number of genes relevant in growth and
      inflammation were quantified. RESULTS: Loss of one STAT3 allele in gp130(757F/F)
      mice reduced the frequency and rate of tumor development because of inhibition of
      proliferation-induced glandular hyperplasia. There was also a concomitant
      reduction in the degree of inflammatory infiltration and cytokine and chemokine
      expression, angiogenesis, and expression of metalloproteinases and growth
      factors. Antimicrobial treatment of gp130(757F/F) mice slowed tumor growth
      coincident with reduced macrophage and neutrophil infiltration. CONCLUSIONS:
      Activation of STAT3 and the microbial environment are pivotal for gastric tumor
      initiation and development in the gp130(757F/F) mouse, thus supporting the notion
      that STAT3 activation may play a role in human gastric cancer development.

PMID- 17030179
TI  - Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling
      and prostaglandin E2 pathway.
AB  - BACKGROUND & AIMS: Accumulating evidence indicates that prostaglandin E(2)
      (PGE(2)), a downstream product of cyclooxygenase 2 (COX-2), plays a key role in
      gastric tumorigenesis. The Wnt pathway is also suggested to play a causal role in
      gastric carcinogenesis. However, the molecular mechanism remains poorly
      understood of how the Wnt and PGE(2) pathways contribute to gastric
      tumorigenesis. To investigate the role of Wnt and PGE(2) in gastric cancer, we
      have generated transgenic mice that activate both pathways and examined their
      phenotypes. METHODS: We constructed K19-Wnt1 transgenic mice expressing Wnt1 in
      the gastric mucosa using the keratin 19 promoter. We then crossed K19-Wnt1 mice
      with another transgenic line, K19-C2mE, to obtain K19-Wnt1/C2mE compound
      transgenic mice. The K19-C2mE mice express COX-2 and microsomal prostaglandin E
      synthase-1 (mPGES-1) in the stomach, showing an increased gastric PGE(2) level.
      We examined the gastric phenotypes of both K19-Wnt1 and K19-Wnt1/C2mE mice.
      RESULTS: K19-Wnt1 mice had a significant suppression of epithelial
      differentiation and developed small preneoplastic lesions consisting of
      undifferentiated epithelial cells with macrophage accumulation. Importantly,
      additional expression of COX-2 and mPGES-1 converted the preneoplastic lesions in
      the K19-Wnt1 mice into dysplastic gastric tumors by 20 weeks of age. Notably, we
      found mucous cell metaplasia in the glandular stomach of the K19-Wnt1/C2mE mice
      as early as 5 weeks of age, before the dysplastic tumor development. CONCLUSIONS:
      Wnt signaling keeps the gastric progenitor cells undifferentiated. Simultaneous
      activation of both Wnt and PGE(2) pathways causes dysplastic gastric tumors
      through the metaplasia-carcinoma sequence.

PMID- 17030180
TI  - APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal
      tumor formation and progression.
AB  - BACKGROUND & AIMS: Synchronous activation of the Wnt signaling pathway, mostly
      because of loss of function of the APC tumor suppressor, and of the oncogenic
      KRAS-signaling pathway is very frequent in colorectal cancer and is associated
      with poor prognosis. METHODS: We have generated a compound transgenic mouse
      model, KRAS(V12G)/Apc(+/1638N), to recapitulate the human disease and compared it
      with single transgenic littermates. RESULTS: Compound mutant mice are
      characterized by a 10-fold increase in tumor multiplicity and by accelerated
      tumor progression, resulting in strongly enhanced morbidity and mortality. Tumors
      from compound mutant mice proliferate faster and show decreased levels of
      apoptosis. Several lines of evidence indicate that the observed increase in tumor
      multiplicity and malignant transformation is caused by the synergistic activation
      of Wnt signaling in cells with oncogenic KRAS and loss-of-function Apc mutations.
      Activated KRAS is known to induce tyrosine phosphorylation of beta-catenin,
      leading to its release from E-cadherin at the adherens junction. This results in
      an increased beta-catenin pool in the cytoplasma, its subsequent translocation to
      the nucleus, and the transcriptional activation of Wnt downstream target genes.
      Accordingly, intestinal tumors from KRAS(V12G)/Apc(+/1638N) mice show a
      significant increase in cells with nuclear accumulation of beta-catenin when
      compared with Apc(+/1638N) animals. Moreover, Apc/KRAS-mutant embryonic stem
      cells show a significantly enhanced beta-catenin/T-cell factor-mediated
      transcriptional activation, accompanied by increased beta-catenin nuclear
      localization. CONCLUSIONS: This KRAS-induced increase in Wnt/beta-catenin
      signaling may enhance the plasticity and self-renewal capacity of the tumor, thus
      resulting in the drastically augmented tumor multiplicity and malignant behavior
      in compound mutant animals.

PMID- 17030181
TI  - Human thioredoxin-1 ameliorates experimental murine colitis in association with
      suppressed macrophage inhibitory factor production.
AB  - BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with
      antioxidative and redox-regulating functions. In this study, we investigated the
      significance of TRX in patients with inflammatory bowel disease (IBD) and the
      ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and
      macrophage migration inhibitory factor (MIF) levels were measured in patients
      with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)
      induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and
      control mice. We further evaluated the effect of recombinant human TRX (rhTRX)
      administration on DSS-induced colitis and colonic inflammation of interleukin
      (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically
      and histologically. Proinflammatory cytokine levels were examined in colonic
      tissues, and MIF levels were measured in colonic tissues and sera in mice. The
      effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX
      and MIF levels were significantly higher in patients with IBD than normal
      controls, and TRX levels correlated with disease activity. TRX significantly
      ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice.
      Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues
      was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF
      levels in colonic tissues and sera were significantly lower in TRX-TG mice than
      in wild-type mice, irrespective of DSS administration. Anti-TRX treatment
      exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX
      suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a
      potential as a novel therapeutic agent for the treatment of IBD.

PMID- 17030182
TI  - The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel
      disease in a murine model.
AB  - BACKGROUND & AIMS: The recently proposed Inflammatory Reflex describes an
      interaction between the vagus nerve and peripheral macrophages, resulting in
      attenuation of proinflammatory cytokine release in response to systemic exposure
      to bacterial endotoxin. The purpose of this study was to determine whether a
      similar vagus/macrophage axis modulates the inflammatory responses in the colon
      in mice. METHODS: We assessed the Disease Activity Index (DAI), macroscopic and
      histologic damage, serum amyloid-P level, and myeloperoxidase activity in colitis
      induced by administration of dextran sodium sulfate (DSS) in healthy and
      vagotomized C57BL/6 and in mice deficient in macrophage-colony stimulating factor
      (M-CSF)-induced and in hapten-induced colitis. A pyloroplasty was performed in
      vagotomized mice. RESULTS: DAI, macroscopic and histologic scores,
      myeloperoxidase activity, levels of serum amyloid-P, and colonic tissue levels of
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were increased
      significantly in vagotomized mice 5 days post-DSS and 3 days after hapten-induced
      colitis compared with sham-operated mice that received DSS or the hapten.
      Pretreatment with nicotine significantly decreased each of these markers in
      vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham
      operated DSS-treated mice. Conversely, hexamethonium treatment significantly
      increased each of these markers in the sham-operated DSS-treated mice. Vagotomy
      had no effect on the colitis in M-CSF-deficient mice. CONCLUSIONS: The vagus
      nerve plays a counterinflammatory role in acute colitis via a macrophage
      dependent mechanism, involving hexamethonium-sensitive nicotinic receptors. The
      identification of a counterinflammatory neural pathway would open new therapeutic
      avenues for treating acute exacerbations of inflammatory bowel disease.

PMID- 17030183
TI  - Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor
      knockout mouse.
AB  - BACKGROUND & AIMS: The G-protein-coupled receptor GPR39 is a member of a family
      that includes the receptors for ghrelin and motilin. Recently the peptide
      obestatin was identified as a natural ligand for GPR39. The objective of this
      study was to gain insight into the biological function of the GPR39 receptor.
      METHODS: GPR39(-/-) mice were generated and analyzed. RESULTS: Endogenous GPR39
      expression was detected in the brain (septum-amygdala) and the gastrointestinal
      system (parietal cells, enterocytes, neurons, and pancreas). Gastric emptying of
      a solid meal (measured by the (14)C octanoic breath test) in GPR39(-/-) mice was
      accelerated significantly with a gastric half-emptying time of 49.5 +/- 2.2
      minutes compared with 86.9 +/- 8.4 minutes in GPR39(+/+) mice. A more effective
      expulsion of distally located pellets (30%-75% of length) was observed in the
      colon of GPR39(-/-) mice. Four hours after pylorus ligation, the volume of
      gastric secretion was increased significantly (GPR39(-/-): 638 +/- 336 microL;
      GPR39(+/+): 225 +/- 170 microL), but gastric acid secretion was unchanged. The
      mature body weight and body fat composition of GPR39(-/-) mice was significantly
      higher compared with GPR39(+/+) mice, but this was not related to hyperphagia
      because 24-hour food intake did not differ between both genotypes. In contrast,
      deficiency of the GPR39 receptor led to reduced hyperphagia after fasting. The
      cholesterol levels were increased significantly in the GPR39(-/-) mice.
      CONCLUSIONS: Our data partially confirm and extend the described in vivo effects
      of obestatin and suggest that this peptide plays a functional role in the
      regulation of gastrointestinal and metabolic function through interaction with
      the GPR39 receptor.

PMID- 17030184
TI  - Nitric oxide-induced down-regulation of beta-catenin in colon cancer cells by a
      proteasome-independent specific pathway.
AB  - BACKGROUND & AIMS: We have previously reported that nitric oxide could induce the
      death of colon cancer cells. Because an inappropriate activation of beta-catenin
      has been associated with intestinal cell malignant transformation, we explored
      whether nitric oxide could affect beta-catenin expression and function. METHODS:
      Human colon cancer cell lines were treated with the nitric oxide donor glyceryl
      trinitrate (GTN) before analyzing beta-catenin expression by immunofluorescence,
      immunoblotting, and immunoprecipitation methods and its transcriptional activity
      using a luciferase reporter gene driven by a T-cell factor-responsive promotor.
      RESULTS: GTN induces beta-catenin degradation and down-regulates its
      transcriptional activity in colon cancer cells. This effect is preceded by GTN
      induced tyrosine nitration of beta-catenin, together with its dephosphorylation
      on serine 33, 37, and 45 and threonine 41. GTN-induced beta-catenin degradation
      involves proteases that are sensitive to a broad-spectrum caspase inhibitor, z
      VAD-fmk, and to serine protease inhibitors N-tosyl-L-phenylalaline chloromethyl
      ketone (TPCK) and [4-(2-aminoethyl)-benzenesulfonylfluoride] (AEBSF), whereas the
      ubiquitin/proteasome pathway is not involved. Interestingly, only TPCK and AEBSF
      restore beta-catenin transcriptional activity and preserve beta-catenin nuclear
      localization in GTN-treated colon cancer cells. CONCLUSIONS: Exposure of colon
      cancer cells to nitric oxide unraveled a so-far-unidentified mechanism of beta
      catenin regulation. The protein is nitrated and dephosphorylated, and its
      transcriptional activity is reduced through degradation by a TPCK and AEBSF
      sensitive protease.

PMID- 17030186
TI  - Glial-derived neurotrophic factor modulates enteric neuronal survival and
      proliferation through neuropeptide Y.
AB  - BACKGROUND & AIMS: Glial-derived neurotrophic factor (GDNF) promotes the survival
      and proliferation of enteric neurons. Neuropeptide Y (NPY) is an important
      peptide regulating gastrointestinal motility. The role of NPY on the survival and
      proliferation of enteric neurons is not known. We examined the effects of GDNF on
      the expression and release of NPY from enteric neurons and the role of NPY in
      promoting enteric neuronal proliferation and survival. METHODS: Studies were
      performed in primary enteric neuronal cultures and NPY knockout mice (NPY(-/-)).
      GDNF-induced expression of NPY was assessed by reverse-transcription polymerase
      chain reaction (RT-PCR), immunocytochemistry, and enzyme-linked immunosorbent
      assay. Using NPY-siRNA and NPY-Y1 receptor antagonist, we examined the role of
      NPY in mediating the survival and proliferation effects of GDNF. Gastrointestinal
      motility was assessed by measuring gastric emptying, intestinal transit, and
      isometric muscle recording from intestinal muscle strips. RESULTS: GDNF induced a
      significant increase in NPY messenger RNA and protein expression in primary
      enteric neurons and the release of NPY into the culture medium. NPY (1 mumol/L)
      significantly increased proliferation of neurons and reduced apoptosis. In the
      presence of NPY-siRNA and NPY-Y1 receptor antagonist or in enteric neurons
      cultured from NPY(-/-) mice, GDNF-mediated neuronal proliferation and survival
      was reduced. NPY increased the phosphorylation of Akt, a downstream target of the
      PI-3-kinase pathway. In NPY(-/-) mice, there were significantly fewer nNOS
      containing enteric neurons compared with wild-type (WT) mice. NPY(-/-) mice had
      accelerated gastric emptying and delayed intestinal transit compared with WT
      mice. CONCLUSIONS: We demonstrate that NPY acts as an autocrine neurotrophic
      factor for enteric neurons.

PMID- 17030185
TI  - IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal
      epithelial barrier dysfunction.
AB  - BACKGROUND & AIMS: Tumor necrosis factor (TNF) plays a critical role in
      intestinal disease. In intestinal epithelia, TNF causes tight junction disruption
      and epithelial barrier loss by up-regulating myosin light chain kinase (MLCK)
      activity and expression. The aim of this study was to determine the signaling
      pathways by which TNF causes intestinal epithelial barrier loss. METHODS: Caco-2
      cells that were either nontransfected or stably transfected with human TNF
      receptor 1 (TNFR1) or TNFR2 and mouse colonocytes were used for physiologic,
      morphologic, and biochemical analyses. RESULTS: Colitis induced in vivo by
      adoptive transfer of CD4(+)CD45RB(hi) T cells was associated with increased
      epithelial MLCK expression and myosin II regulatory light chain (MLC)
      phosphorylation as well as morphologic tight junction disruption. In vitro
      studies showed that TNF caused similar increases in MLCK expression and MLC
      phosphorylation, as well as barrier dysfunction, in Caco-2 monolayers only after
      interferon (IFN)-gamma pretreatment. This reductionist model was therefore used
      to determine the molecular mechanism by which IFN-gamma and TNF synergize to
      cause intestinal epithelial barrier loss. IFN-gamma priming increased TNFR1 and
      TNFR2 expression, and blocking antibody studies showed that TNFR2, but not TNFR1,
      was required for TNF-induced barrier dysfunction. Transgenic TNFR2, but not
      TNFR1, expression allowed IFN-gamma-independent TNF responses. CONCLUSIONS: IFN
      gamma primes intestinal epithelia to respond to TNF by inducing TNFR2 expression,
      which in turn mediates TNF-induced MLCK-dependent barrier dysfunction. The data
      further suggest that epithelial TNFR2 blockade may be a novel approach to restore
      barrier function in intestinal disease.

PMID- 17030187
TI  - The motogenic effects of cyclic mechanical strain on intestinal epithelial
      monolayer wound closure are matrix dependent.
AB  - BACKGROUND & AIMS: Complex deformation during normal digestion due to peristalsis
      or villous motility may be trophic for the intestinal mucosa. Because tissue
      fibronectin is increased in inflammatory states that may accompany mucosal
      injury, we evaluated the effects of cyclic mechanical strain and fibronectin on
      intestinal epithelial monolayer wound closure in Caco-2 and IEC-6 intestinal
      epithelial cells. METHODS: Wounds created in intestinal epithelial monolayers
      were subjected to cyclic deformation. Wound closure was assessed by morphometry
      using microscopic imaging. Cell signals were assessed by Western blot and
      confocal microscopy. RESULTS: Mechanical strain stimulated wound closure on
      fibronectin but inhibited closure on collagen in Caco-2 and IEC-6 cells. The
      effect was independent of proliferation or cell spreading. Myosin light chain
      (MLC) and extracellular signal-regulated kinase (ERK) were phosphorylated in
      response to strain in confluent monolayers on both collagen and fibronectin.
      Blocking MLC or ERK phosphorylation inhibited the motogenic effect of strain on
      fibronectin. Although phosphorylated MLC was redistributed to the leading edge of
      migrating cells following 6 hours of strain on collagen and fibronectin,
      phosphorylated ERK was redistributed to the lamellipodial edge only on
      fibronectin. CONCLUSIONS: Strain promotes intestinal epithelial wound closure by
      a pathway requiring ERK and MLC kinase. Fibronectin-dependent ERK redistribution
      in response to strain in confluent migrating cells may explain the matrix
      dependence of the motogenic effect. Repetitive deformation stimulates intestinal
      epithelial proliferation on a collagen substrate, but not fibronectin.
      Deformation may exert matrix-dependent effects on intestinal epithelial cells,
      promoting epithelial restitution in fibronectin-rich tissue and proliferation in
      fibronectin-poor mucosa.

PMID- 17030188
TI  - TUCAN (CARD8) genetic variants and inflammatory bowel disease.
AB  - BACKGROUND & AIMS: The identification of the association between Crohn's disease
      (CD) and NOD2 (CARD15) confirmed both the heritability of CD and highlighted the
      role of the nuclear factor kappaB (NFkappaB) pathway in disease pathogenesis.
      Other susceptibility loci exist. TUCAN (CARD8) is located beneath a CD peak of
      linkage on chromosome 19q. TUCAN is expressed in the gut and is a negative
      regulator of NFkappaB, making it an excellent candidate gene for gastrointestinal
      inflammation. METHODS: Ten single nucleotide polymorphisms (SNP) across TUCAN
      were genotyped in 365 controls, 372 patients with CD, and 373 patients with
      ulcerative colitis. A diagnostic panel for CD was constructed using smoking
      status and TUCAN, NOD2, IBD5, NOD1, and TNFSF15 data. RESULTS: We demonstrate
      significant association between a TUCAN SNP and CD (OR 1.35, P = .0083). The
      association was more pronounced with disease affecting sites other than the colon
      (odds ratio, 1.52) and NOD2-negative CD (odds ratio, 1.50). Combination of these
      data with smoking and NOD2, IBD5, NOD1, and TNFSF15 status demonstrated very
      strong associations with CD and high sensitivities (96.3%), specificities
      (99.4%), and likelihood ratios (12.8) for CD, although further work will be
      needed before this model can be translated into direct clinical utility.
      CONCLUSIONS: We have shown an association between a likely functional
      polymorphism in TUCAN and CD. The combination of these data in a genetic panel
      suggests that clinicians may soon be able to translate genetic advances into
      direct benefits for patients.

PMID- 17030189
TI  - CD36 is important for chylomicron formation and secretion and may mediate
      cholesterol uptake in the proximal intestine.
AB  - BACKGROUND & AIMS: Studies are aimed to determine the role of CD36 in intestinal
      lipid absorption. METHODS: Knock-out (KO) and wild-type (WT) lymph fistula mice
      were used to study fatty acids (FA) and cholesterol uptake, and chylomicron
      formation and secretion. Uptake of FA and cholesterol was studied by using
      sucrose polybehenate and fecal dual isotope methods, respectively. RESULTS: The
      CD36 KO exhibited significant accumulation of dietary cholesterol in the
      intestinal lumen at the end of 6-hour lipid infusion and significant reduction of
      dietary cholesterol transport into the lymph. Fecal dual isotope studies,
      however, did not show any significant difference in cholesterol uptake,
      suggesting that given sufficient time, the KO intestine could compensate for the
      reduced cholesterol uptake observed in the acute lymph fistula studies. Recovery
      of dietary FA in the intestinal lumen was comparable between WT and KO,
      consistent with the sucrose polybehenate study. However, the KO mice accumulated
      more, albeit not significantly, dietary triacylglycerols in the intestine,
      followed by a significant reduction in lymphatic transport. The ratio of
      intestinal dietary triacylglycerols to FA was not higher in WT than KO, arguing
      against impaired lipid esterification. It is rather a deficiency in the formation
      and secretion of chylomicrons, as supported by the significantly less
      apolipoprotein B-48 and the smaller, albeit not significantly, lipoprotein
      particles secreted into the lymph of the KO. CONCLUSIONS: CD36 may play an
      important role in chylomicron formation and secretion and may also facilitate
      cholesterol uptake in the proximal intestine.

PMID- 17030190
TI  - Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of
      human hepatoma cells.
AB  - BACKGROUND & AIMS: The Raf kinase inhibitor protein (RKIP) has been identified as
      a suppressor of the mitogen-activated protein kinase (MAPK) pathway. Loss of RKIP
      function promotes tumor metastasis in prostate cancer and melanoma. The insulin
      like growth factor I (IGF-I)-mediated MAPK cascade is often activated in
      hepatocellular carcinoma (HCC), but the role of RKIP in the molecular
      pathogenesis of these tumors is unknown. This study was performed to evaluate the
      role of RKIP in the development of HCC. METHODS: The levels of RKIP expression in
      HCC tumor and corresponding peritumoral tissues were determined by
      immunohistochemistry and Western blot analysis. The underlying mechanisms of RKIP
      were assessed with immunoblot analysis, Raf kinase activity assay, cell
      proliferation, and migration assays after either overexpression or knockdown of
      RKIP expression in HCC cell lines. RESULTS: RKIP expression is down-regulated in
      human HCC compared with adjacent peritumoral tissues. Low RKIP levels were
      correlated with enhanced extracellular signal-regulated-kinase (ERK)/MAPK pathway
      activation. Reconstitution experiments antagonized IGF-I-mediated MAPK pathway
      activation, resulting in reduced nuclear accumulation of phospho-ERK. In
      contrast, knockdown of RKIP expression using small interfering RNA induced
      activation of the ERK/MAPK pathway. Ectopic expression of RKIP altered HCC cell
      proliferation and migration. CONCLUSIONS: Our findings indicate that down
      regulation of RKIP expression is a major factor in activation of the IGF
      I/ERK/MAPK pathway during human hepatocarcinogenesis.

PMID- 17030191
TI  - Prickle-1 negatively regulates Wnt/beta-catenin pathway by promoting Dishevelled
      ubiquitination/degradation in liver cancer.
AB  - BACKGROUND & AIMS: Aberrant activation of Wnt signaling due to accumulation of
      beta-catenin has been linked to tumorigenesis. Mutations of beta-catenin, APC,
      and axins are important but not frequent enough to be accountable for the
      accumulation of beta-catenin in human hepatocellular carcinoma (HCC). In this
      study, we characterized the roles of Prickle-1, a Dishevelled (Dvl)-associated
      protein, in regulation of Wnt/beta-catenin activity in HCC. METHODS: The
      expression levels of human Prickle-1 and Dvl3 were examined in HCC cell lines and
      human HCC samples. The interaction and effects of Prickle-1 on Dvl3, the Wnt/beta
      catenin pathway, and cell growth were assessed in HCC cell lines. RESULTS: We
      showed that Prickle-1 bound with Dvl3 and facilitated Dvl3
      ubiquitination/degradation, and this was through its destruction box (D-box)
      motifs. Enforced expression of Prickle-1 significantly reduced the Wnt/beta
      catenin activity and tumorigenic properties of HCC cells. Clinicopathologic
      analysis showed that underexpression of Prickle-1 was significantly associated
      with overexpression of Dvl3, beta-catenin accumulation (P = .023), and larger
      tumor size (P = .030). CONCLUSIONS: Our results have elucidated a novel
      mechanistic relationship between Prickle-1 and Dvl3 in the Wnt/beta-catenin
      pathway. The facilitation of Prickle-1 on Dvl3 degradation and the suppression of
      beta-catenin activity and cell growth suggest that Prickle-1 is a negative
      regulator of the Wnt/beta-catenin signaling pathway and is a putative tumor
      suppressor in human HCCs.

PMID- 17030192
TI  - Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP
      sensitive K+ channel activity.
AB  - BACKGROUND & AIMS: Changes in mitochondrial energy metabolism promoted by
      uncoupling proteins (UCPs) are often found in metabolic disorders. We have
      recently shown that hypertriglyceridemic (HTG) mice present higher mitochondrial
      resting respiration unrelated to UCPs. Here, we disclose the underlying mechanism
      and consequences, in tissue and whole body metabolism, of this mitochondrial
      response to hyperlipidemia. METHODS: Oxidative metabolism and its response to
      mitochondrial adenosine triphosphate (ATP)-sensitive K+ channel (mitoK(ATP))
      agonists and antagonists were measured in isolated mitochondria, livers, and
      mice. RESULTS: Mitochondria isolated from the livers of HTG mice presented
      enhanced respiratory rates compared with those from wild-type mice. Changes in
      oxygen consumption were sensitive to adenosine triphosphate (ATP), diazoxide, and
      5-hydroxydecanoate, indicating they are attributable to mitochondrial ATP
      sensitive K+ channel (mitoK(ATP)) activity. Indeed, mitochondria from HTG mice
      presented enhanced swelling in the presence of K+ ions, sensitive to mitoK(ATP)
      agonists and antagonists. Furthermore, mitochondrial binding to fluorescent
      glibenclamide indicates that HTG mice expressed higher quantities of mitoK(ATP).
      The higher content and activity of liver mitoK(ATP) resulted in a faster
      metabolic state, as evidenced by increased liver oxygen consumption and higher
      body CO(2) release and temperature in these mice. In agreement with higher
      metabolic rates, food ingestion was significantly larger in HTG mice, without
      enhanced weight gain. CONCLUSIONS: These results show that primary hyperlipidemia
      leads to an elevation in liver mitoK(ATP) activity, which may represent a
      regulated adaptation to oxidize excess fatty acids in HTG mice. Furthermore, our
      data indicate that mitoK(ATP), in addition to UCPs, may be involved in the
      control of energy metabolism and body weight.

PMID- 17030193
TI  - Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human
      hepatic stellate cells.
AB  - BACKGROUND & AIMS: Accumulating evidence indicates that acetaldehyde (AcCHO) is
      one of the main mediators of fibrogenesis in alcoholic liver disease. AcCHO
      stimulates synthesis of fibrillar collagens in hepatic stellate cells, but the
      molecular events directly involved in the activation of collagen genes are
      debatable. METHODS: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      is a nuclear receptor that is expressed in stellate cells, and its activation by
      specific ligands inhibits collagen synthesis. In this study, we evaluated the
      effects of AcCHO on PPARgamma transcriptional activity and its correlation with
      the AcCHO-induced collagen synthesis in hepatic stellate cells. RESULTS: AcCHO
      treatment inhibited ligand-dependent and -independent PPARgamma transcriptional
      activity, and this effect was correlated with an increased phosphorylation of a
      mitogen-activated protein kinase site at serine 84 of the human PPARgamma.
      Transfection of the PPARgammaSer84Ala mutant completely prevented the effect of
      AcCHO on PPARgamma activity and in parallel abrogated the induction of collagen
      gene expression by AcCHO. The effect of AcCHO on PPARgamma activity and
      phosphorylation was blocked by extracellular signal-regulated kinase (ERK) 1/2
      and protein kinase C (PKC)delta inhibitors as well as by catalase, suggesting
      that hydrogen peroxide is involved in the molecular cascade responsible for
      PPARgamma phosphorylation via activation of the PKCdelta/ERK pathway.
      Furthermore, inhibition of c-Abl completely abrogated the effect of AcCHO on
      either PPARgamma function or collagen synthesis; in addition, expression of the
      PPARgammaSer84Ala mutant prevented the profibrogenic signals mediated by c-Abl
      activation. CONCLUSIONS: Our results showed that the induction of collagen
      expression by AcCHO in stellate cells is dependent on PPARgamma phosphorylation
      induced by a hydrogen peroxide-mediated activation of the profibrogenic c-Abl
      signaling pathway.

PMID- 17030194
TI  - Selection of a multiple drug-resistant hepatitis B virus strain in a liver
      transplanted patient.
AB  - BACKGROUND & AIMS: Sequential anti-hepatitis B virus (HBV) therapy may lead to
      the selection of complex mutants. We analyzed the genetic and phenotypic
      evolution of the viral quasispecies of a patient who received successively
      lamivudine, add-on adefovir+lamivudine, followed by lamivudine+adefovir+hepatitis
      B immunoglobulins (HBIg) after orthotopic liver transplantation. METHODS: For
      genotypic analysis, a 1310-bp region of the polymerase gene was amplified,
      cloned, and sequenced. Huh-7 cells were transfected to compare the replication
      fitness of HBV mutants and their susceptibility to drugs. RESULTS: At baseline,
      all HBV genomes carried a wild-type (wt) RT gene but 22% harbored the sP120S and
      55% the sC107stop mutations within the surface (S) gene associated with vaccine
      escape. Following viral breakthrough to lamivudine monotherapy, a complex mixture
      of lamivudine-resistant HBV strains prevailed. Interestingly, among these mutants
      emerged a population harboring only the rtL180M+A181V mutations, conferring
      lamivudine-resistance in vitro. After addition of adefovir to the ongoing
      treatment, viral load dropped, and the patient underwent an orthotopic liver
      transplantation and received HBIg. As viral load rose again, a single viral
      population was progressively selected, harboring the rtV173L+L180M+A181V+N236T
      and sP120S mutations. In vitro, this last mutant showed a level of replication
      reduced by only 30% compared to wt HBV and a strong resistance to both lamivudine
      (>1000-fold) and adefovir (>10-fold). It remained sensitive to tenofovir both in
      vitro and in vivo. CONCLUSIONS: We report the selection of a complex HBV mutant
      that escaped the antiviral pressure of lamivudine, adefovir, and HBIg, and
      provide insight on the process of selection via genotypic and phenotypic
      analysis.

PMID- 17030195
TI  - A tumor progression model for hepatocellular carcinoma: bioinformatic analysis of
      genomic data.
AB  - BACKGROUND & AIMS: It is widely recognized that genomic abnormalities underpin
      the development of human cancers. Aberrant patterns of chromosomal changes may
      represent useful information that can be used in classifying the complex traits
      of liver cancer cases for the genetic events involved in tumor carcinogenesis,
      tumor progression, and prognosis. METHODS: Genome-wide chromosomal aberrations of
      158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by
      comparative genomic hybridization (CGH). By application of a self-organizing tree
      algorithm, statistically significant CGH events were used to construct an
      evolutionary tree that could infer patient subgroups with different degrees of
      tumor progression. The key CGH events in the subgroups were identified. The
      clinical significance of the groupings and the key CGH events were examined.
      RESULTS: Based on the patterns of significant chromosomal aberrations derived, 3
      HCC subgroups organized in an evolutionary tree were identified. The groupings
      possessed information reflecting the degrees of tumor progression, including
      numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease
      outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events
      associated with the early development of HCC. Gain of 3q22-24, however, was
      identified as 1 of the late genomic events found to be associated with tumor
      recurrence and poor overall patient survival. CONCLUSIONS: A tumor progression
      model for HCC was constructed and revealed chromosomal imbalances that were
      significantly associated with clinical pathologic characteristics of the disease.
      This model explains a significant part of the variations in clinical outcome
      among HCC patients.

PMID- 17030196
TI  - Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and
      pancreatic cancer: a meta-analysis.
AB  - BACKGROUND & AIMS: Increasing evidence suggests that a low folate intake and
      impaired folate metabolism may be implicated in the development of
      gastrointestinal cancers. We conducted a systematic review with meta-analysis of
      epidemiologic studies evaluating the association of folate intake or genetic
      polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central
      enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic
      cancer. METHODS: A literature search was performed using MEDLINE for studies
      published through March 2006. Study-specific relative risks were weighted by the
      inverse of their variance to obtain random-effects summary estimates. RESULTS:
      The summary relative risks for the highest versus the lowest category of dietary
      folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal
      squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal
      adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic
      cancer (1 case-control, 4 cohort); there was no heterogeneity among studies.
      Results on dietary folate intake and risk of gastric cancer (9 case-control, 2
      cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype,
      which is associated with reduced enzyme activity, was associated with an
      increased risk of esophageal squamous cell carcinoma, gastric cardia
      adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and
      pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates
      were statistically significant. Studies of the MTHFR A1298C polymorphism were
      limited and inconsistent. CONCLUSIONS: These findings support the hypothesis that
      folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.

PMID- 17030197
TI  - Will screening colonoscopy disappear and transform gastroenterology practice?
      Threats to clinical practice and recommendations to reduce their impact: report
      of a consensus conference conducted by the AGA Institute Future Trends Committee.
AB  - The AGA Institute Future Trends Committee (FTC) developed this report based on a
      consensus conference it convened on April 1-2, 2006, in Washington, DC. The
      report was prepared for the FTC by Carol Regueiro, MD, a medical writer under
      contract to the AGA Institute, and Michael Stolar, PhD, staff liaison to the FTC.
      It was approved by the FTC on July 12, 2006, and accepted by the AGA Institute
      Governing Board on July 22, 2006. This report reflects the panel's assessment of
      information available at the time of the conference. Readers should view this
      report in the context of data that will continue to accumulate and facts that may
      change after its creation.

PMID- 17030198
TI  - AGA Institute medical position statement on the use of endoscopic therapy for
      gastroesophageal reflux disease.
AB  - This document presents the official recommendations of the AGA Institute on
      "Endoscopic Therapy for Gastroesophageal Reflux Disease." It was approved by the
      Clinical Practice and Economics Committee on June 20, 2006, and by the AGA
      Institute Governing Board on July 24, 2006.

PMID- 17030199
TI  - AGA Institute technical review on the use of endoscopic therapy for
      gastroesophageal reflux disease.

PMID- 17030200
TI  - Abdominal distention: old hypotheses and new concepts.

PMID- 17030201
TI  - Use of ribavirin in patients with chronic HCV genotype 1: when enough is really
      enough.

PMID- 17030202
TI  - Adding fuel to the fire: STAT3 priming of gastric tumorigenesis.

PMID- 17030203
TI  - Genomic decoding of hepatocellular carcinoma.

PMID- 17030212
TI  - Acetaminophen protein adducts: is acetaminophen to blame?

PMID- 17030215
TI  - Adenoma or carcinoma: an important but difficult distinction.

PMID- 17030216
TI  - Steroid-independent Crohn's disease patients also benefit from combination
      therapy of infliximab plus azathioprine.

PMID- 17030218
TI  - Clinical approach to the prostate: an update.
AB  - Prostatic disease continues to present clinicians with challenges. Although giant
      strides have been made in the medical and surgical management of benign prostatic
      hyperplasia, many fundamental questions about its pathogenesis, progression, and
      treatment efficacy remain unanswered. Prostate cancer also continues to be an
      area in which progress is needed despite major recent advancements. Numerous
      debates that include the value of prostate-specific antigen screening and
      appropriate roles for each of the numerous therapeutic modalities await
      resolution. For millions of patients who suffer from prostatitis, a major
      breakthrough is yet to come. Current treatment regimens for prostatitis remain
      ineffective at best. Contemporary approaches to the pathogenesis, diagnosis, and
      treatment of benign prostatic hyperplasia, prostate cancer, and prostatitis are
      discussed in this review.

PMID- 17030219
TI  - Inflammatory disorders of the prostate and the distal genital tract.
AB  - Inflammatory disease of the prostate and distal genital tract is emerging as a
      major health problem because it is estimated that up to 15% of adult men may be
      affected at some point in their lives. Clinically, the diagnosis of "prostatitis"
      refers to multiple disorders that cause pelvic pain and discomfort, ranging from
      acute bacterial infection to complex conditions that may not necessarily be
      caused by prostatic inflammation. Because the traditional etiology-based
      classification system did not always correlate with symptoms and therapeutic
      efficacy, a new classification of prostatitis has been suggested by the National
      Institutes of Health. New imaging techniques such as high-resolution transrectal
      ultrasonography (TRUS) and MR imaging provide exquisite anatomic detail and often
      play a crucial role in the evaluation of these patients.

PMID- 17030220
TI  - Transrectal sonography in prostate evaluation.
AB  - Prostate cancer is the most prevalent newly diagnosed noncutaneous malignancy in
      men. With the continued use of prostate-specific antigen screening, there has
      been a dramatic rise in the number of prostate biopsied performed. Transrectal
      ultrasonography (TRUS) is an essential tool used for detecting prostate pathology
      and performing prostate biopsies. This article review the indications and
      principles of TRUS of the prostate, the technique of TRUS, and controversies
      pertaining to prostate core biopsy.

PMID- 17030221
TI  - Benign prostatic hyperplasia: a review and ultrasound classification.
AB  - Benign prostatic hyperplasia (BPH) is reviewed, including definition,natural
      history, diagnosis, and brief discussion of clinical management. Transrectal
      ultrasound is used to demonstrate the gross anatomy and natural history of BPH
      and its role in diagnosis and treatment strategies. A potentially useful
      ultrasound classification of BPH based on the gross anatomic classification of
      Randall is illustrated.

PMID- 17030222
TI  - Prostate cancer imaging--what the urologic oncologist needs to know.
AB  - Appropriate imaging for prostate cancer patients depends on the clinical disease
      state of the patient and the question being asked. For patients who do not have a
      cancer diagnosis, ultrasound is the standard approach, in combination with a
      sextant biopsy. In the future, contrast-enhanced ultrasound and MR imaging
      directed biopsy may improve biopsy yield and decrease biopsy number. For
      clinically localized disease, endorectal coil MR imaging and bone scanning may
      play a role in patients who have risk factors for extracapsular extension, but
      more data are needed to define the role of MR spectroscopy and lymphtrophic
      nanoparticle MR imaging. In the rising prostate-specific antigen (PSA) setting
      after definitive local therapy, endorectal coil MR imaging may help define local
      recurrence, whereas bone scanning can be useful in the setting of higher PSA or
      rapid PSA velocity.

PMID- 17030223
TI  - MR imaging and MR spectroscopy in prostate cancer management.
AB  - Currently, endorectal coil MR imaging has the ability to improve accuracy in
      staging of localized prostate cancer. The addition of MR spectroscopic imaging
      has further improved the sensitivity of MR imaging for intraprostatic tumor
      localization. Additional refinements and techniques are expected to further
      improve the performance of MR imaging for prostate cancer imaging and to aid in
      patient management. Further studies are required to identify the ideal role for
      MR imaging in the diagnosis and management of prostate cancer.

PMID- 17030224
TI  - Image-guided brachytherapy for prostate cancer.
AB  - Prostate brachytherapy offers and effective treatment for organ-confined prostate
      carcinoma. It is rapidly delivered compared with external beam radiation therapy
      or surgery and well tolerated by patients. Volumetric imaging and image guidance
      play critical roles in patient selection, treatment planning, treatment delivery,
      and postimplant assessment. Costs, availability and ease of use often dictate the
      local and regional differences in imaging approach, whether ultrasound, CT, or
      MR. Future volumetric image developments may permit multimodality image fusion to
      integrate tumor-specific imaging such as MR spectroscopy or positron emission
      tomography/CT into real-time ultrasound, CT, or MR.

PMID- 17030225
TI  - Imaging the pediatric prostate.
AB  - The prostate gland is not often the target of imaging in children but may be
      imaged during investigation of symptoms related to the lower genitourinary tract
      such as hematuria, urinary retention, dysuria, and incontinence or during an
      evaluation for suspected congenital anomalies. Ultrasound and voiding
      cystourethrography are useful for initial evaluation of congenital and neoplastic
      disorders of the prostate. MR imaging and CT are useful in delineating more
      detailed anatomy before surgical planning and in determining the organ of origin
      in a patient who has a large pelvic mass.

PMID- 17030227
TI  - Clinical and pathologic perspectives on aspirin sensitivity and asthma.
AB  - Aspirin and other nonsteroidal anti-inflammatory drugs that inhibit COX-1 induce
      unique nonallergic reactions, consisting of attacks of rhinitis and asthma. These
      hypersensitivity reactions occur in a subset of asthmatic subjects, thus
      identifying them as having this exclusive clinical presentation. We refer to
      these patients as having aspirin-exacerbated respiratory disease, a disease
      process that produces devastating eosinophilic inflammation of both the upper and
      lower respiratory tracts. This review focuses on a description of patients with
      aspirin-exacerbated respiratory disease, methods available to diagnose their
      condition, the unique ability of all nonsteroidal anti-inflammatory drugs that
      inhibit COX-1 to cross-react with aspirin, an update on pathogenesis, and current
      thoughts about treatment.

PMID- 17030228
TI  - The role of leukotrienes in airway inflammation.
AB  - Cysteinyl leukotrienes (cysLTs) are a class of closely structurally related lipid
      molecules, originally described as slow-reacting substance of anaphylaxis, with a
      myriad of biologic functions. These activities include producing smooth muscle
      contraction and mucus secretion, recruiting allergic inflammatory cells,
      modulating cytokine production, influencing neural transmission, and altering
      structural changes in the airway. Administration of cysLTs to animals and human
      subjects reproduces many features of allergic inflammation and asthma.
      Leukotriene (LT) blockers have independent efficacy in asthma and improve
      pulmonary function when added to inhaled steroids. Conversely, blockade of this
      pathway both in animals and in human subjects results in important reductions in
      inflammation and its consequences and might reduce structural changes of
      remodeling. These data collectively make a compelling case for an important role
      of cysLTs in airway inflammation and asthma. However, the magnitude of effect of
      anti-LTs is smaller than that of corticosteroids, and there is more variability
      in benefit of LT blockade than is seen with inhaled steroids. In addition, adding
      anti-LTs to inhaled steroids in asthmatic patients does not appear to produce
      added anti-inflammatory benefit. Genetic polymorphisms and environmental factors,
      such as tobacco smoke exposure, might underlie some of the heterogeneity of
      response to LT blockers.

PMID- 17030229
TI  - Selection of patients for aspirin desensitization treatment.

PMID- 17030230
TI  - Mild persistent asthma: is any treatment needed?
AB  - Asthma treatment guidelines are intended to relieve symptoms and to prevent
      complications such as exacerbations, airway remodeling, and death. The existing
      recommendations are based on a combination of evidence and expert opinion. Recent
      data raise questions about the need for chronic controller therapy for those
      patients at the very low end of the asthma-severity continuum. Although these
      data are not sufficient to warrant a change in guidelines, the new information
      points out the need for large, long-term studies on the treatment of mild
      persistent asthma, with an emphasis on exacerbations, remodeling, and the
      relationship between these outcomes and markers of asthma control.

PMID- 17030231
TI  - Salmeterol response is not affected by beta2-adrenergic receptor genotype in
      subjects with persistent asthma.
AB  - BACKGROUND: Recent studies suggest that there might be an association between
      albuterol use and worsening asthma in patients homozygous for arginine (Arg/Arg)
      at codon 16 of the beta-receptor. However, it is not known whether similar
      responses occur in Arg/Arg patients receiving long-acting beta2-agonists.
      OBJECTIVE: We sought to evaluate the effects of variation in the beta2-adrenergic
      receptor gene (ADRB2) on clinical response to salmeterol administered with
      fluticasone propionate. METHODS: Subjects (n = 183) currently receiving short
      acting beta2-agonists were randomized to twice-daily therapy with salmeterol, 50
      microg, administered with fluticasone propionate, 100 microg, in a single inhaler
      or daily therapy with montelukast for 12 weeks, followed by a 2- to 4-day run-out
      period. RESULTS: There was sustained and significant improvement (P < .001) over
      baseline in all measures of asthma control in subjects receiving salmeterol,
      regardless of Arg16Gly genotype. Morning peak expiratory flow in subjects with
      the Arg/Arg genotype showed 89.0 +/- 16.1 L/min improvement over baseline
      compared with 93.7 +/- 12.7 L/min for Gly/Gly subjects and 92.5 +/- 11.9 L/min
      for Arg/Gly subjects. Pairwise changes were similar for Arg/Arg compared with
      Gly/Gly or Arg/Gly genotypes (estimated differences, 4.7 L/min and 3.5 L/min,
      respectively). Responses did not appear to be modified by haplotype pairs. During
      the run-out period, all subjects had predictable and similar decreases in
      measures of asthma control, with no differences between genotypes. CONCLUSION:
      Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing
      with an inhaled corticosteroid. CLINICAL IMPLICATIONS: Analyses from this study
      indicate that genetic polymorphisms leading to Arg16Gly sequence changes within
      the beta2-adrenergic receptor do not affect patients' responses to recommended
      asthma therapy with salmeterol and fluticasone propionate.

PMID- 17030232
TI  - Buffering airway acid decreases exhaled nitric oxide in asthma.
AB  - BACKGROUND: The human airway is believed to be acidified in asthma. In an acidic
      environment nitrite is converted to nitric oxide (NO). OBJECTIVE: We hypothesized
      that buffering airway lining fluid acid would decrease the fraction of exhaled NO
      (F(ENO)). METHODS: We treated 28 adult nonsmoking subjects (9 healthy control
      subjects, 11 subjects with mild intermittent asthma, and 8 subjects with
      persistent asthma) with 3 mL of 10 mmol/L phosphate buffered saline (PBS) through
      a nebulizer and then serially measured F(ENO) levels. Six subjects also received
      PBS mouthwash alone. RESULTS: F(ENO) levels decreased after buffer inhalation.
      The maximal decrease occurred between 15 and 30 minutes after treatment; F(ENO)
      levels returned to pretreatment levels by 60 minutes. The decrease was greatest
      in subjects with persistent asthma (-7.1 +/- 1.0 ppb); this was more than in
      those with either mild asthma (-2.9 +/- 0.3 ppb) or healthy control subjects (
      1.7 +/- 0.3 ppb, P < .001). Levels did not decrease in subjects who used PBS
      mouthwash. CONCLUSION: Neutralizing airway acid decreases F(ENO) levels. The
      magnitude of this change is greatest in persistent asthma. These data suggest
      that airway pH is a determinant of F(ENO) levels downstream from NO synthase
      activation. CLINICAL IMPLICATIONS: Airway biochemistry modulates F(ENO) levels.
      For example, nitrite is converted to NO in the airway, particularly the inflamed
      airway, by means of acid-based chemistry. Thus airway pH should be considered in
      interpreting clinical F(ENO) values. In fact, PBS challenge testing integrates
      airway pH and F(ENO) analysis, potentially improving the utility of F(ENO) as a
      noninvasive test for the type and severity of asthmatic airway inflammation.

PMID- 17030233
TI  - Preterm delivery and asthma: a systematic review and meta-analysis.
AB  - BACKGROUND: Accumulating evidence suggests that reduced duration of pregnancy
      predicts increased risk of asthma, but the studies published have been
      inconsistent. OBJECTIVE: We sought to synthesize the evidence on the relation
      between preterm delivery and the risk of asthma later in life and to assess
      differences between the studies as potential sources for heterogeneity of the
      results. METHODS: We conducted a MEDLINE search (until the end of May 2005). The
      outcome was asthma. The determinant of interest was preterm delivery defined as a
      gestational age of less than 37 weeks. RESULTS: We identified 19 articles that
      provided estimates for the meta-analysis. The summary effect estimates for asthma
      (fixed-effects odds ratio, 1.074 [95% CI, 1.072-1.075]; heterogeneity P = .000;
      random-effects odds ratio, 1.366 [95% CI, 1.303-1.432]) showed an increased risk
      in relation to preterm delivery, with substantial heterogeneity between study
      specific estimates. The effect of preterm delivery on asthma was stronger in
      cross-sectional studies; studies with broad outcome criteria, a small sample
      size, and a younger study population; and studies conducted in English-speaking
      populations, outside Europe, and published more recently. In metaregression,
      adjusting for other determinants, the effect estimate was significantly
      associated only with the mean age of the study population. CONCLUSIONS: The
      weight of evidence shows that preterm babies have an increased risk of asthma
      compared with term babies. CLINICAL IMPLICATIONS: Recognition of prematurity as a
      determinant of asthma emphasizes the importance of active treatment of
      physiologic airflow obstruction and a need for special preventive measures
      against known environmental determinants of asthma in preterm babies.

PMID- 17030234
TI  - Ligation of intercellular adhesion molecule 3 induces apoptosis of human blood
      eosinophils and neutrophils.
AB  - BACKGROUND: Intercellular adhesion molecule 3 (ICAM-3) is highly expressed on
      human granulocytes, including eosinophils and neutrophils, but the functions of
      ICAM-3 in these cells are not well understood. OBJECTIVE: Our studies test the
      hypothesis that ICAM-3 regulates granulocyte apoptosis. METHODS: Intercellular
      adhesion molecule 3 was activated by a mAb that recognizes an ICAM-3 epitope that
      binds its ligand, CD11a/CD18. In some experiments with eosinophils, recombinant
      human IL-5 or GM-CSF was added to mimic in vivo antiapoptotic conditions.
      Staining with annexin V-fluorescein isothiocyanate and propidium iodide
      identified apoptotic cells. RESULTS: Binding of ICAM-3 increased apoptosis of
      both eosinophils (18 and 48 hours) and neutrophils (18 hours). At 18 hours,
      eosinophil apoptosis increased from 31.4% +/- 3.5 SE (IgG control) to 45.2% +/-
      3.8 SE (anti-ICAM-3), and neutrophil apoptosis increased from 48% +/- 4.1 SE (IgG
      control) to 55.3% +/- 4.5 SE (anti-ICAM-3). At 48 hours, eosinophil apoptosis
      increased 2-fold under baseline conditions and also in the presence of
      recombinant human IL-5 or GM-CSF. In both eosinophils and neutrophils, incubation
      with a blocking antibody against CD18 integrins blunted ICAM-3-induced apoptosis.
      In eosinophils, blocking peptides for caspases 8 and 9, proteases critical to
      apoptosis, also decreased ICAM-3-induced apoptosis to control levels. CONCLUSION:
      Through its effect on eosinophil and neutrophil apoptosis, ICAM-3 may be an
      important anti-inflammatory molecule that can oppose the proinflammatory effects
      of IL-5 and GM-CSF. CLINICAL IMPLICATIONS: These findings provide a mechanism for
      apoptotic clearance of eosinophils and neutrophils involved in allergic
      inflammation that, unlike necrosis, does not cause nonspecific tissue injury.

PMID- 17030235
TI  - Fungal zymosan induces leukotriene production by human mast cells through a
      dectin-1-dependent mechanism.
AB  - BACKGROUND: Fungi are capable of causing or exacerbating inflammatory disease in
      the airways. We have previously demonstrated that zymosan and peptidoglycan
      induce the production of cysteinyl leukotrienes from human mast cells. However,
      the mechanisms of pathogen-induced leukotriene production by immune effector
      cells are very poorly understood. The coreceptor dectin-1, through a Syk tyrosine
      kinase-dependent pathway, can mediate some responses to fungal challenge, but its
      expression by mast cells and its involvement in lipid mediator responses have not
      been assessed. OBJECTIVE: In the current study, the potential role of dectin-1 in
      zymosan-induced leukotriene production from human mast cells was examined.
      METHODS: Human mast cells were examined for dectin-1 mRNA and protein expression.
      Human mast cells were incubated with either zymosan or peptidoglycan in the
      presence or absence of specific inhibitors for dectin-1 or Syk tyrosine kinase
      and mediator production examined. RESULTS: Human mast cells were found to express
      a functional isoform of dectin-1. Both peptidoglycan and zymosan induced
      significant amounts of leukotriene (LT)-B4 and LTC4. The dectin-1 inhibitors
      laminarin and glucan phosphate reduced the LTC4 response to zymosan by more than
      60% but did not alter peptidoglycan responses. Inhibitors of Syk tyrosine kinase
      activity significantly decreased LTC4 production in response to both
      peptidoglycan and zymosan. CONCLUSION: These data demonstrate mast cell
      expression of the coreceptor dectin-1 and a role for this molecule in the
      generation of cysteinyl leukotrienes. CLINICAL IMPLICATIONS: These findings
      suggest new approaches to the selective inhibition of lipid mediator production
      in response to fungal infection or exposure.

PMID- 17030236
TI  - Subpollen particles: carriers of allergenic proteins and oxidases.
AB  - BACKGROUND: Pollen is known to induce allergic asthma in atopic individuals,
      although only a few inhaled pollen grains penetrate into the lower respiratory
      tract. OBJECTIVE: We sought to provide evidence that subpollen particles (SPPs)
      of respirable size, possessing both antigenic and redox properties, are released
      from weed pollen grains and to test their role in allergic airway inflammation.
      METHODS: The release of SPPs was analyzed by means of microscopic imaging and
      flow cytometry. The redox properties of SPPs and the SPP-mediated oxidative
      effect on epithelial cells were determined by using redox-sensitive probes and
      specific inhibitors. Western blotting and amino acid sequence analysis were used
      to examine the protein components of the SPP. The allergenic properties of the
      SPP were determined in a murine model of experimental asthma. RESULTS: Ragweed
      pollen grains released 0.5 to 4.5 microm of SPPs on hydration. These contained
      Amb a 1, along with other allergenic proteins of ragweed pollen, and possessed
      nicotinamide adenine dinucleotide (reduced) or nicotinamide adenine dinucleotide
      phosphate (reduced) [NAD(P)H] oxidase activity. The SPPs significantly increased
      the levels of reactive oxygen species (ROS) in cultured cells and induced
      allergic airway inflammation in the experimental animals. Pretreatment of the
      SPPs with NAD(P)H oxidase inhibitors attenuated their capacity to increase ROS
      levels in the airway epithelial cells and subsequent airway inflammation.
      CONCLUSIONS: The allergenic potency of SPPs released from ragweed pollen grains
      is mediated in tandem by ROS generated by intrinsic NAD(P)H oxidases and
      antigenic proteins. CLINICAL IMPLICATIONS: Severe clinical symptoms associated
      with seasonal asthma might be explained by immune responses to inhaled SPPs
      carrying allergenic proteins and ROS-producing NAD(P)H oxidases.

PMID- 17030237
TI  - Gene-environment interactions with CD14 C-260T and their relationship to total
      serum IgE levels in adults.
AB  - BACKGROUND: Both endotoxin exposure and a single nucleotide polymorphism in one
      of its receptors, CD14 C-260T, have been separately associated with total serum
      IgE levels. Furred pets might also influence IgE levels through their effects on
      endotoxin levels. However, how these factors interact to influence total IgE
      levels is not well known, especially in adults. OBJECTIVE: We sought to
      investigate the interactive relationship between endotoxin levels, pet exposure,
      and CD14 C-260T genotype on total serum IgE levels in adults. METHODS: Mothers
      enrolled in an ongoing cohort study were genotyped for the CD14 C-260T
      polymorphism. Exposure to pets was assessed by using questionnaires and dust
      allergen levels collected in the home. Endotoxin exposure was estimated by using
      dust collected from mothers' bedroom floors. The primary outcome measure was
      total serum IgE level. RESULTS: CD14 C-260T genotype was assessed in 517 (85.2%)
      of the 607 women enrolled in the study. The CD14 C-260T genotype was
      significantly associated with total IgE levels; however, this relationship
      appeared to be modified by the level of endotoxin exposure. Similar interactions
      between CD14 C-260T and pet exposure were not seen, regardless of the measure of
      pet exposure used. CONCLUSIONS: The CD14 C-260T genotype and endotoxin exposure
      together appear to influence total serum IgE levels in adults. The absence of a
      similar gene-environment interaction for pet exposure suggests separate
      mechanisms of action. CLINICAL IMPLICATIONS: A common polymorphism in the
      endotoxin receptor, CD14 C-260T, and dust endotoxin levels in the home might
      interact to influence total serum IgE levels into adulthood.

PMID- 17030238
TI  - IL-13 receptor alpha 2: a regulator of IL-13 and IL-4 signal transduction in
      primary human fibroblasts.
AB  - BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their
      use of a common receptor complex comprising IL-13 receptor alpha 1 (IL-13Ralpha1)
      and IL-4 receptor alpha (IL-4Ralpha). The nonsignaling receptor IL-13 receptor
      alpha 2 (IL-13Ralpha2) binds IL-13 with high affinity and specificity and is
      believed to be a decoy receptor for IL-13. OBJECTIVE: We sought to examine the
      inhibitory effects of soluble and membrane-bound IL-13Ralpha2 on IL-13- and IL-4
      mediated effects. METHODS: Primary human fibroblasts were grown from
      endobronchial biopsy specimens obtained from volunteers. Upregulation of IL
      13Ralpha2 mRNA was measured by means of RT-PCR, and the level of surface
      expression was measured by means of FACS. RESULTS: We found that a recombinant
      soluble form of IL-13Ralpha2 blocked the effects of IL-13, but not IL-4, in
      fibroblasts in vitro. However, we found that the transmembrane form of IL
      13Ralpha2 could attenuate both IL-13 and IL-4 responses, even though the response
      to TNF-alpha was unaffected. Furthermore, we found that IL-13Ralpha2 became
      associated with IL-4Ralpha in the presence of IL-4. Addition of a blocking
      antibody to the extracellular domain of IL-13Ralpha2 restored responses of both
      IL-13 and IL-4. CONCLUSION: The ability of IL-13Ralpha2 to regulate IL-4 was
      previously unrecognized in primary airway cells. These data reveal a novel role
      for IL-13Ralpha2 as a negative regulator of both IL-13 and IL-4 signaling in
      human bronchial fibroblasts. CLINICAL IMPLICATIONS: It appears that IL-13Ralpha2
      might be a powerful suppressor of TH2-mediated responses and thus represents a
      potential therapeutic target for the treatment of asthma.

PMID- 17030240
TI  - Hyperosmolar conjunctival provocation for the evaluation of nonspecific
      hyperreactivity in healthy patients and patients with allergy.
AB  - BACKGROUND: Tissue hyperreactivity of target organs to nonspecific stimuli is
      known to be an important factor in influencing the clinical picture of allergic
      disease. OBJECTIVE: To identify the sensitivity and specificity of a hyperosmolar
      conjunctival provocation test in predicting conjunctival hyperreactivity and to
      relate this reactivity to the presence of ocular discomfort in subjects with and
      without allergy. METHODS: In 50 healthy patients and 19 patients with allergic
      conjunctivitis during remission phase, symptoms of ocular discomfort triggered by
      nonspecific stimuli were identified and graded with a discomfort score. Subjects
      were then challenged with a glucose solution at increasing concentrations (from
      10% to 50%). The glucose concentration that elicited 2+ conjunctival hyperemia
      was considered the provoking dose. The response to this hyperosmolar provocation
      in subjects with ocular discomfort was compared with that of asymptomatic
      subjects. Sensitivity and specificity of the test in predicting conjunctival
      hyperreactivity were analyzed. RESULTS: Six of 50 healthy subjects and 12 of 19
      subjects with allergy complained of ocular discomfort after exposure to
      nonspecific stimuli. The hyperosmolar provocation test discriminated between
      subjects with and without ocular discomfort (mean provoking dose: 39.5% +/- 5%
      and 47.5% +/- 5% glucose, respectively; P < .001). Forty percent glucose was the
      optimal threshold dose that demonstrated the highest sensitivity and specificity
      for prediction of conjunctival hyperreactivity. Discomfort scores were
      significantly related to provoking dose values (P < .05). CONCLUSION: This study
      provides a standardized procedure to detect nonspecific conjunctival
      hyperreactivity independent of underlying atopy. CLINICAL IMPLICATIONS:
      Hyperosmolar provocation test may be useful for identifying conjunctival
      hyperreactivity in subjects with and without allergy with a history of ocular
      discomfort.

PMID- 17030239
TI  - Filaggrin loss-of-function mutations predispose to phenotypes involved in the
      atopic march.
AB  - BACKGROUND: Childhood eczema often precedes the development of asthma and
      allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function
      mutations in the gene encoding the epidermal barrier protein filaggrin were
      reported to be predisposing factors for eczema and concomitant asthma, suggesting
      a possible role in disease transition. OBJECTIVE: We aimed to assess the
      importance of filaggrin loss-of-function mutations in the susceptibility to
      eczema and associated clinical phenotypes. METHODS: The filaggrin mutations were
      genotyped and tested for association with allergic disorders in 2 large European
      populations including 1092 children with eczema. RESULTS: Highly significant
      association of the filaggrin null mutations with eczema and concomitant asthma
      was replicated. Moreover, we found that these mutations predispose to asthma,
      allergic rhinitis, and allergic sensitization only in the presence of eczema. We
      show that the presence of 2 filaggrin null alleles is an independent risk factor
      for asthma in children with eczema, and that the 2 investigated mutations account
      for about 11% of eczema cases in the German population. CONCLUSION: These results
      lend strong support to the role of filaggrin in the pathogenesis of eczema and in
      the subsequent progression along the atopic march. The fact that previous
      expression of eczema is a prerequisite for the manifestation of allergic airways
      disease and specific sensitization highlights the importance of the epidermal
      barrier in the pathogenesis of these disorders. CLINICAL IMPLICATIONS: Our
      results suggest that the maintenance and repair of the epidermal barrier in
      infants with eczema may prevent the subsequent development of allergic airways
      disease.

PMID- 17030241
TI  - Purification of a novel aminopeptidase from the pollen of Parietaria judaica that
      alters epithelial integrity and degrades neuropeptides.
AB  - BACKGROUND: Parietaria judaica pollen is a common cause of pollinosis in the
      Mediterranean area. OBJECTIVE: This study sought to purify and characterize the
      peptidase responsible for the majority of proteolytic activity present in the
      pollen extract of P judaica, and to investigate its contribution to the allergic
      response. METHODS: A serial of chromatographic steps was applied to isolate the
      peptidase from P judaica's pollen, and its biochemical properties were
      determined. Bioactive peptides present in the airways were incubated with the
      peptidase, and their degradation was visualized by direct protein sequencing. In
      addition, we measured the cellular detachment, by methylene blue binding assay,
      of an airway-derived epithelial cell line (A549) in the presence of the
      peptidase, and visualized, by Western blot, the degradation of proteins from
      intercellular junctions. RESULTS: We purified a 98-kDa peptidase from the pollen
      of P judaica that was classified as an aminopeptidase on the basis of its
      biochemical properties and internal amino acid sequence. The aminopeptidase was
      able to degrade bioactive peptides. Moreover, the aminopeptidase caused cellular
      detachment of A549 cell line and degradation of occludin and E-cadherin.
      CONCLUSION: Our results suggest that the P judaica aminopeptidase can alter the
      integrity of the epithelium barrier by degrading occludin as well as E-cadherin.
      In addition, P judaica aminopeptidase can degrade bioactive peptides, which can
      exacerbate the overall bronchoconstrictive effect detected in asthmatic lungs.
      CLINICAL IMPLICATIONS: The novel aminopeptidase described here could constitute a
      relevant therapeutic target in the treatment of allergic disorders induced by the
      pollen of P judaica.

PMID- 17030242
TI  - Biophysical determinants of toluene diisocyanate antigenicity associated with
      exposure and asthma.
AB  - BACKGROUND: Toluene diisocyanate (TDI), a widely used aromatic diisocyanate with
      the potential to cause asthma, reacts with albumin in the airway fluid, which
      acts as a carrier protein for chemical presentation to the immune system.
      Structural elucidation of TDI-albumin conjugates is crucial to understanding the
      human immune response to TDI exposure. OBJECTIVE: Investigate the dependence of
      TDI's antigenicity on the biophysics of exposure and its association with TDI
      asthma. METHODS: Toluene diisocyanate-albumin conjugates were generated by
      exposing albumin to TDI in liquid or vapor phase (liquid or vapor TDI-albumin,
      respectively). Conjugates were characterized by native gel electrophoresis and
      matrix-assisted laser desorption/ionization-mass spectrometry, and used as
      antigens in ELISA assays for serum specific-IgE and IgG. RESULTS: The physical
      phase of TDI (vapor vs liquid) affects the formation of TDI-albumin conjugates,
      with measurable differences in the amount of TDI per albumin molecule, migration
      in native gels, matrix-assisted laser desorption/ionization-mass spectrometry
      mass/charge spectra, and antigenicity. Vapor TDI-albumin conjugates were
      recognized by IgE from 44% of subjects with TDI asthma, whereas liquid TDI
      albumin conjugates are recognized by IgE from only 17% of these patients. A
      significant (P < .05) association between TDI exposure and vapor TDI-albumin
      specific serum IgG was also observed. CONCLUSION: Biophysics of TDI exposure
      substantially affects formation of TDI-albumin conjugates recognized by the
      immune system in association with exposure and asthma. CLINICAL IMPLICATIONS: The
      data suggest that serology may help identify TDI asthmatics and exposed workers
      if the appropriate form of TDI is used as the antigenic basis for analysis.

PMID- 17030243
TI  - Exposure to Alternaria alternata in US homes is associated with asthma symptoms.
AB  - BACKGROUND: Exposure to the fungus Alternaria alternata is a risk factor for
      asthma. Few studies have examined Alternaria exposures in indoor environments.
      OBJECTIVE: We examined whether exposure to A alternata in US homes was associated
      with asthma-related outcomes. METHODS: The data for this study were collected as
      part of the National Survey of Lead and Allergens in Housing. This cross
      sectional study surveyed a nationally representative sample of 831 housing units
      inhabited by 2456 individuals in 75 different locations throughout the United
      States. An interviewer-administered questionnaire obtained information on
      demographics, household characteristics, and occupants' health status. Exposure
      to A alternata was assessed by measuring concentrations of A alternata antigens
      in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust
      samples were collected from a bed, a sofa, or a chair, and from bedroom, living
      room, and kitchen floors. RESULTS: Lifetime prevalence of doctor-diagnosed asthma
      was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the
      past 12 months. The prevalence of current symptomatic asthma increased with
      increasing Alternaria concentrations in US homes; higher levels of A alternata
      antigens increased the odds of having asthma symptoms in the past year (relative
      to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the
      2nd tertile; and 1.84, 95% CI, 1.18-2.85 for the 3rd tertile). CONCLUSION:
      Exposure to A alternata in US homes is associated with active asthma symptoms.
      CLINICAL IMPLICATIONS: Measures that reduce indoor exposure to A alternata may
      help control asthma exacerbations.

PMID- 17030244
TI  - Adherence and persistence with fluticasone propionate/salmeterol combination
      therapy.
AB  - BACKGROUND: Pharmacy database medication refill studies provide a panoramic view
      of medication-taking behavior in patients nationally. OBJECTIVE: To investigate
      fluticasone propionate/salmeterol combination (FSC) adherence, including the
      factors associated with refill adherence in a large national pharmacy database.
      METHODS: Adherence and persistence were documented for 12 months from date of
      initial FSC prescription in 5504 patients who filled their medication at a
      nationwide pharmacy chain. RESULTS: On average, patients filled enough medication
      to cover 22.2% of days. More than half the patients filled a 30-day prescription
      only once over the 1-year interval. Higher adherence levels were associated with
      being male, being older than 35 years, having a comorbid disorder, a having a
      copay of 1.01 dollar to 10 dollars, previous beta2-agonist use, and a
      prescription for higher-dose FSC. CONCLUSION: This pharmacy database study
      portrays medication adherence levels to be considerably lower than those reported
      in most clinical trials, suggests that most adults taking FSC obtain a single
      fill before abandoning their controller medication, and indicates a need for a
      reappraisal of current treatment guidelines and educational strategies for both
      providers and patients. CLINICAL IMPLICATIONS: For many patients, filling of a
      controller medication is markedly discrepant with practice guidelines.
      Reappraisal of both the guidelines and strategies to implement them is in order.

PMID- 17030245
TI  - Human subjects without peanut allergy demonstrate T cell-dependent, TH2-biased,
      peanut-specific cytokine and chemokine responses independent of TH1 expression.
AB  - BACKGROUND: Peanut allergy is a major cause of anaphylaxis. Regulation of immune
      responses to peanut allergen, particularly why sensitization does not usually
      progress to allergic reactions, is not well investigated. Most studies focus
      exclusively on serologic responses and individuals with peanut allergy.
      OBJECTIVE: We sought to determine the existence, prevalence, and nature of peanut
      specific, T cell-dependent cytokine and chemokine responses of adults who eat
      peanut without having symptoms. METHODS: We developed systems to examine specific
      immunity in peanut-tolerant individuals who had (1) negative histories and
      negative peanut skin test responses, (2) negative histories and positive peanut
      skin test responses, and (3) clinically apparent peanut allergy. After primary
      culture of PBMCs restimulated with whole peanut extract, we quantified responses
      characteristic of TH1 (IFN-gamma and CXCL10) and TH2-like immunity (IL-5, IL-13,
      CCL17, and CCL22) using ultrasensitive ELISAs. Antigen-presenting cell
      costimulatory requirements (CD4, HLA-DR, CD80/86, and cytotoxic T lymphocyte
      associated antigen 4 [CTLA4] Ig) were determined. RESULTS: T cell-dependent,
      peanut-specific IL-5, IL-13, and CCL22 were common in peanut-tolerant
      individuals, regardless of whether they had positive or negative skin test
      responses. These were blocked by anti-CD4 and were dependent on CD28/CD86
      costimulation. None of the 70 individuals studied had demonstrable IFN-gamma or
      CXCL10 responses to peanut. All demonstrated TH1 and TH2 responses to the
      ubiquitous recall antigen streptokinase. CONCLUSIONS: Qualitatively similar and
      quantitatively increasing peanut-specific TH2 responses in the consistent absence
      of putatively protective TH1 immunity were found in both peanut-tolerant
      individuals and those with peanut allergy. CLINICAL IMPLICATIONS: The continuum
      of responses between individuals with negative and individuals with positive skin
      test results, rather than TH1 versus TH2 bias, might be important in peanut
      allergy.

PMID- 17030246
TI  - Cloning and characterization of profilin (Pru du 4), a cross-reactive almond
      (Prunus dulcis) allergen.
AB  - BACKGROUND: The identity of allergenic almond proteins is incomplete. OBJECTIVE:
      Our objective was to characterize patient IgE reactivity to a recombinant and
      corresponding native almond allergen. METHODS: An almond cDNA library was
      screened with sera from patients with allergy for IgE binding proteins. Two
      reactive clones were sequenced, and 1 was expressed. The expressed recombinant
      allergen and its native counterpart (purified from unprocessed almond flour) were
      assayed by 1-dimensional and 2-dimensional gel electrophoresis, dot blot, and
      ELISA, and screened for cross-reactivity with grass profilin. RESULTS: The 2
      selected clones encoded profilin (designated Pru du 4) sequences that differed by
      2 silent mutations. By dot-blot analyses, 6 of 18 patient sera (33%) reacted with
      the recombinant Pru du 4 protein, and 8 of 18 (44%) reacted with the native form.
      ELISA results were similar. Almond and ryegrass profilins were mutually
      inhibitable. Two-dimensional immunoblotting revealed the presence of more than 1
      native almond profilin isoform. The strength of reactivity of some patients'
      serum IgE differed markedly between assays and between native and recombinant
      profilins. CONCLUSION: Almond nut profilin is an IgE-binding food protein that is
      cross-reactive with grass pollen profilin and is susceptible to denaturation,
      resulting in variable reactivity between assay types and between patients.
      CLINICAL IMPLICATIONS: Serum IgE of nearly half of the tested patients with
      almond allergy reacts with almond nut profilin. Because most patients also had
      pollinosis, the well-known cross-reactivity between pollen and food profilins
      could account for this pattern of reactivity.

PMID- 17030247
TI  - The atopy patch test in the diagnostic workup of suspected food-related symptoms
      in children.
AB  - BACKGROUND: There is an increasing need to develop test instruments that make
      oral food challenges superfluous. OBJECTIVE: We sought to study the utility of
      atopy patch tests (APTs) in the diagnostic workup of food allergy. METHODS: We
      investigated 437 children (median age, 13 months; 90% with atopic dermatitis)
      referred for evaluation of suspected food allergy. Specific serum IgE (sIgE)
      measurements, skin prick tests (SPTs), APTs, and controlled oral food challenges
      were performed. RESULTS: We analyzed 873 oral challenges with cow's milk, hen's
      egg, wheat, and/or soy. One thousand seven hundred single APTs were performed. As
      a single parameter, the APTs showed the best specificity compared with sIgE
      measurements, SPTs, or both. Combining the APT with either the SPT or sIgE
      measurement resulted in improved sensitivity and specificity. Decision points for
      sIgE measurement and for the SPT showed lower values when combined with a
      positive APT result. Correctly bypassing an oral food challenge with combined
      testing, including APTs, only between 0.5% and 7% (99% predicted probability) and
      between 6% and 14% (using 95% predicted probability) of children would fulfill
      the criteria for avoiding an oral food challenge. CONCLUSION: Although the
      predictive capacity of the APT is improved when combined with sIgE measurement or
      the SPT, oral food challenges become superfluous in only 0.5% to 14% of study
      patients. In addition, the APT is time consuming and demands a highly experienced
      test evaluator. CLINICAL IMPLICATIONS: For daily clinical practice, the APT adds
      only a small predictive value to the standard SPT and sIgE measurement in the
      diagnostic workup of suspected food-related symptoms in our study population.

PMID- 17030248
TI  - Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and
      allergic contact dermatitis.
AB  - BACKGROUND: IL-31 is produced by activated T lymphocytes, preferentially by TH2
      cells. Transgenic mice overexpressing IL-31 have a phenotype resembling allergic
      dermatitis in human subjects. OBJECTIVE: We sought to evaluate the potential
      importance of IL-31 in the pathogenesis of human T cell-mediated skin diseases.
      METHODS: We analyzed total RNA taken from 149 skin biopsy specimens from patients
      with atopic dermatitis (AD), allergic contact dermatitis (ACD), or psoriasis in
      comparison with specimens taken from patients with healthy skin (n = 13) by using
      quantitative real-time PCR for the expression of TH1/TH2 cytokines. RESULTS: We
      found statistically increased mRNA levels of IL-31 in biopsy specimens taken from
      patients with AD, irrespective of the severity of the disease and serum IgE
      levels. Moreover, IL-31 mRNA levels were strongly increased in many biopsy
      specimens taken from patients with ACD. However, no increased transcription of IL
      31 could be detected in biopsy specimens taken from psoriatic plaques. A
      comparison of mRNA levels of IL-31 with TH1 or TH2 cytokines demonstrates a
      correlation of the expression of IL-31 with IL-4 and IL-13 but not with IFN
      gamma. No significant increase of IL-31 receptor mRNA could be detected in any
      disease, whereas the second receptor subunit of IL-31, the oncostatin M receptor,
      seems to be enhanced transcribed in patients with psoriasis. CONCLUSION: IL-31
      expression is not only increased in patients with AD but also in those with ACD,
      2 pruritic skin disorders. In both types of eczema, expression of IL-31 is
      associated with the expression of the TH2 cytokines IL-4 and IL-13. CLINICAL
      IMPLICATIONS: IL-31 might contribute not only to the development of AD but also
      to ACD-provoked skin inflammation.

PMID- 17030249
TI  - Mumps resurgence in the United States.
AB  - The recent mumps epidemic in the central United States has generated a large
      amount of public concern. A total of 2597 mumps cases have been reported in the
      United States in 11 states since January 1, 2006, representing a marked
      resurgence of mumps in a single year. The majority of these recent cases have
      occurred in college students age 18 to 25 years. Most were vaccinated with 2
      doses of measles, mumps, and rubella-containing vaccines. Such outbreaks provide
      an opportunity for clinicians to review the clinical presentation, diagnosis, and
      morbidity of vaccine-preventable infections and also to review immunologic
      mechanisms and practice guidelines that might contribute to poor vaccine
      responses. A review of mumps is provided with discussion of potential mechanisms
      for vaccine failure.

PMID- 17030250
TI  - Direct evidence for a critical role of CD30 in the development of allergic
      asthma.
AB  - BACKGROUND: CD30 is a costimulatory molecule belonging to the TNF receptor
      superfamily that is expressed on activated T and B cells. Several studies have
      demonstrated a positive correlation between expression of CD30 or increased
      levels of soluble CD30 and the development and severity of allergic diseases.
      However, thus far, the evidence for a role of CD30 in allergic diseases, such as
      asthma, is only indirect. OBJECTIVE: The aim of the study was to directly
      investigate the role of CD30 in a murine asthma model. METHODS: CD30-deficient
      (B6.129P2-Tnfrsf8(tm1Mak)/J) and wild-type (WT) mice were immunized to ovalbumin
      (OVA) to induce an asthma-like phenotype and compared in our murine asthma model.
      Moreover, CD30/CD30 ligand signaling was blocked in OVA-immunized WT animals by
      using mAbs against CD30 receptor and its ligand, CD153. RESULTS: The absence of
      CD30 in OVA-immunized CD30-deficient mice resulted in significantly reduced
      airway inflammation, serum IgE levels, and TH2 cytokine levels. The same effect
      was observed when CD30/CD153 signaling was blocked in OVA-immunized WT animals
      with mAbs against CD30 or CD30 ligand. CONCLUSION: Our results directly
      demonstrate that CD30/CD153 interaction plays an important role in the induction
      of TH2 cell-mediated allergic asthma. CLINICAL IMPLICATIONS: These findings
      provide evidence for a role of the costimulatory molecule CD30 in allergic
      asthma.

PMID- 17030251
TI  - Potential involvement of dendritic cells in delayed-type hypersensitivity
      reactions to beta-lactams.
AB  - BACKGROUND: Although the involvement of T cells in delayed reactions to drugs has
      been studied, little is known about the interaction between the drug and the
      antigen-presenting cells. Dendritic cells (DCs) are professional antigen
      presenting cells essential for initiating T-cell responses. Their ability is
      regulated in a process known as maturation, by which they modulate the effector
      immune response. OBJECTIVES: We studied the role of DCs in subjects who had a
      delayed-type hypersensitivity reaction to amoxicillin to assess the effect on the
      pattern of maturation and determine the capacity of DCs to activate T
      lymphocytes. METHODS: We examined the consequences of the interaction between
      monocyte-derived DCs, lymphocytes, and amoxicillin by means of phenotypic and
      functional studies, including endocytosis, proliferation, and cytokine
      production. RESULTS: Amoxicillin drove DCs from hypersensitive subjects to a
      phenotypic and functional semimature status, inducing a T-cell proliferation
      response. CONCLUSIONS: In delayed reactions to amoxicillin, DCs play a relevant
      role in inducing the T-cell responses. These results are useful not only to
      understand the mechanism but potentially as a possible approach to diagnosis.
      CLINICAL IMPLICATIONS: A better understanding of T-cell and DC involvement in
      delayed-type hypersensitivity reactions is needed. This in vitro assay might
      provide clues to the diagnostic evaluation of patients allergic to penicillins.

PMID- 17030252
TI  - Different eicosanoid profile of the hypersensitivity reactions triggered by
      aspirin and celecoxib in a patient with sinusitis, asthma, and urticaria.

PMID- 17030253
TI  - Swimming pool attendance and exhaled nitric oxide in children.

PMID- 17030254
TI  - Correlation of FCERIB gene haplotypes with histamine release from basophils in
      atopic asthma.

PMID- 17030255
TI  - Opposing actions of (R,R)-isomers and (S,S)-isomers of formoterol on T-cell
      function.

PMID- 17030256
TI  - Symmetric, drug-related, intertriginous, and flexural exanthema in a patient with
      polyvalent intolerance to corticosteroids.

PMID- 17030257
TI  - Sensitization to Anisakis simplex: inhalant allergy versus gastroallergic
      anisakiasis.

PMID- 17030259
TI  - Eosinophilic bronchitis and asthma with sputum eosinophilia are different
      entities.

PMID- 17030261
TI  - The metal binding site of the major house dust mite allergen Der p 1.

PMID- 17030267
TI  - Epidemiology of adenocarcinoma of the esophagogastric junction.
AB  - The incidence of adenocarcinoma of the esophagogastric junction has increased
      rapidly in the later half of the twentieth century in the United States and most
      western countries. Although squamous cell carcinoma of the esophagus used to
      predominate, adenocarcinoma of the distal esophagus and esophagogastric junction
      now accounts for more than half of new diagnoses in western countries. There also
      has been a shift from the development of distal gastric cancers to ones in a more
      proximal location. These recent epidemiologic shifts have led to controversy
      regarding the etiology and treatment of adenocarcinoma of the esophagogastric
      junction. Uncertainty still exists with regards to nomenclature and
      classification, risk factors, treatment, and screening and surveillance of
      esophagogastric adenocarcinoma. This article examines the epidemiology and
      etiologies of adenocarcinoma of the esophagogastric junction.

PMID- 17030268
TI  - Pathologic risk factors of adenocarcinoma of the gastric cardia and
      gastroesophageal junction.
AB  - Available evidence supports the existence of two major pathways of neoplastic
      development in the gastroesophageal region: the Barrett pathway, related to
      gastroesophageal reflux disease, and the gastric pathway, related to Helicobacter
      pylori infection. The existence of an independent junctional pathway is
      questionable, and gastroesophageal junction adenocarcinomas share features of
      esophageal and gastric adenocarcinomas. It has been impossible to accommodate all
      data that are provided by different levels and tools of observation in tumors
      that develop in the gastroesophageal region in a single, coherent classification.
      That is why the stratification of pathologic risk in such tumors, and their
      respective precursors, incorporates features from topography, histology,
      immunohistochemistry, and molecular pathology.

PMID- 17030269
TI  - Barrett's esophagus and adenocarcinoma of the gastroesophageal junction: a
      pathologic perspective.
AB  - Barrett's esophagus is defined clinically by the presence of endoscopically
      evident columnar mucosa in the distal esophagus with histopathologic confirmation
      of the presence of intestinal-type epithelium. The etiology of Barrett's
      esophagus is understood poorly, but chronic gastroesophageal reflux disease is
      considered a major contributing factor. Barrett's esophagus is associated with
      the development of adenocarcinoma of the gastroesophageal junction. It is
      believed that the development of a Barrett-type mucosa with intestinal goblet
      type cells is due to an altered process of differentiation of pluripotent
      epithelial stem cells in response to the local injury and repair process. The
      potential identification and isolation of markers for screening purposes and
      possibly prognostic information are areas of considerable clinical and scientific
      interest.

PMID- 17030270
TI  - Evolving role of (18)F-fluorodeoxyglucose positron emission tomography in the
      management of esophageal carcinoma.
AB  - Positron emission tomography (PTE) and PET/CT imaging with (18)F
      fluorodeoxyglucose are metabolic imaging modalities that depict tissues based on
      their level of glucose uptake. PET provides useful information in the primary
      staging of disease. PET performance in detecting locoregional nodal metastases is
      limited; however, it is the most accurate single noninvasive modality for
      detecting distant metastases. It is the imaging modality of choice for whole-body
      scanning in high-risk patients or patients who have clinically suspected
      recurrence, and is particularly helpful in determining which patients are the
      best candidates for surgical cure.

PMID- 17030271
TI  - Adenocarcinoma of the esophagogastric junction: surgical therapy based on 1602
      consecutive resected patients.
AB  - Because of the borderline location between the esophagus and stomach, many
      discrepancies exist in the current literature regarding the etiology,
      classification, and surgical treatment of adenocarcinoma arising at the
      esophagogastric junction. The classification of adenocarcinomas into three types,
      AGE type I, type II, and type III, shows marked differences between the tumor
      entities and is recommended for selection of a proper surgical approach. Complete
      tumor resection and adequate lymphadenectomy are recommended for a good, long
      term prognosis. With better surgical management and standardized procedures, even
      the results in patients with more radical surgical approaches, the abdomino
      thoracic esophagectomy improved.

PMID- 17030272
TI  - Adenocarcinoma of the gastroesophageal junction: benefits of an extended
      lymphadenectomy.
AB  - The incidence of esophageal adenocarcinoma is rising faster the any other cancer
      in the United States. Studies from around the world strongly suggest that for
      early cancers of the lower esophagus and cardia, en bloc esophagogastrectomy
      results in significantly better survival rates than does transhiatal
      esophagogastrectomy.

PMID- 17030273
TI  - Extent of surgical resection for esophageal and gastroesophageal junction
      adenocarcinomas.
AB  - The early-stage lymphatic dissemination in esophageal cancer poses challenges for
      adequate surgical treatment. The role of extensive lymph node dissections remains
      a matter of debate. Results of the only available large randomized controlled
      trial suggest that fit patients who have esophageal cancer are treated best by a
      transthoracic esophagectomy with extended en bloc (two-field) lymphadenectomy.
      For less fit patients or patients who have junctional or cardiac tumors,
      transhiatal esophageal resection could suffice. In patients who have truly
      "early" adenocarcinoma (ie, with high-grade dysplasia or intramucosal carcinoma)
      endoscopic resectional or ablative treatments may be suitable. When the tumor
      invades the submucosal layer, the high risk for lymph node involvement and tumor
      recurrence probably necessitates more extensive treatment schedules for
      definitive cure.

PMID- 17030274
TI  - Gastroesophageal carcinoma: individualized surgical therapy.
AB  - During the twentieth century, surgical management of gastroesophageal carcinoma
      was developed by an establishment of standard procedures with lymph node
      dissection according to the metastatic distribution. The "fear" of invisible
      micrometastasis caused surgeons to perform more aggressive resection with
      lymphadenectomy to control the disease locally. Although several promising
      results of extensive lymph node dissection have been reported, the prognostic
      benefits of extensive surgery have not been proven by prospective randomized
      trials. A novel technology to detect micrometastasis without extensive surgical
      resection is required to gastroesophageal carcinoma. The lymphatic mapping
      technique is one of the attractive candidates for a novel tool to approach this
      issue.

PMID- 17030275
TI  - Cancer of the gastroesophageal junction: combined modality therapy.
AB  - Esophageal cancer, an uncommon, but highly virulent malignancy in the United
      States, will be responsible for nearly 14,000 deaths in the year 2005. The
      prognosis for patients who have adenocarcinoma of the distal esophagus and
      gastroesophageal junction and who are treated with the standard approaches of
      surgery or combined chemoradiation therapy is poor. Recent clinical trials have
      evaluated the use of preoperative chemotherapy followed by surgery, combined
      concurrent preoperative chemoradiotherapy followed by surgery, or definitive
      chemoradiotherapy alone without surgery. This article focuses on recent advances
      in the use of combined modality therapy in adenocarcinoma of the esophagus and
      gastroesophageal junction.

PMID- 17030277
TI  - Body art: piercing, tattooing, and scarification.
AB  - Body art, particularly piercings and tattoos, is becoming more common. Many
      patients get their first piercing or tattoo during adolescence or young
      adulthood. Clinicians should understand the potential complications of these
      procedures and their management. It also is important for clinicians to feel
      comfortable counseling adolescents and their families about practices in safer
      body art facilities.

PMID- 17030278
TI  - Alternative and complementary therapies.
AB  - The field of complementary and alternative medicine (CAM) is broad and diverse,
      comprising numerous therapeutic modalities. CAM therapies are viewed as either an
      adjunct or a complement to conventional treatment. As of 1997, 64% of United
      States medical schools included elective or required CAM courses. The number of
      CAM practitioners in the United States is projected to increase by 88% between
      1994 and 2010, and the number of conventional physicians who incorporate CAM into
      their practices will increase by 16%. Patients and their parents can make various
      health care choices; doctors need to understand and respect these options, and to
      support them, if safe and effective.

PMID- 17030279
TI  - Immunization update: pertussis, meningoccocus, and human papillomavirus.
AB  - New vaccines are being recommended for adolescents at a brisk pace. Immunization
      is an effective preventive measure, and by bringing adolescents in for a medical
      intervention, the new vaccines promise not only to protect adolescents from the
      specific diseases they address, but also to enhance other health care services,
      including screening for other health risk behaviors. This article discusses the
      newest vaccination recommendations for adolescents pertaining to the
      meningococcal and tetanus, diphtheria, and acellular pertussis vaccines and
      reviews the human papillomavirus vaccines developed for use in the United States.
      With the advent of these new vaccines, the potential exists to improve adolescent
      health significantly through prevention, adding new incentive to increase
      adolescent immunization rates for all indicated vaccines.

PMID- 17030280
TI  - Supersize teens: the metabolic syndrome.
AB  - With obesity and type 2 diabetes on the rise in children and adolescents, there
      has been recent interest in the study of the metabolic (insulin resistance)
      syndrome in this population. Characteristics of the syndrome include impaired
      glucose tolerance, hypertension, dyslipidemia, and abdominal obesity. These
      features are known to cluster and convey increased cardiovascular risk over time.
      Screening of children and adolescents is important to the goal of prevention, and
      therapeutic lifestyle modification is the primary treatment modality. When this
      fails, pharmacotherapy aimed at the individual risk factors may be indicated.

PMID- 17030281
TI  - Bariatric surgery in adolescents: an update.
AB  - Bariatric surgery, although not a cure for obesity, can help selected extremely
      obese adolescents achieve significant weight loss and improvement of obesity
      related comorbidities, in conjunction with continued dietary and behavioral
      interventions. This article summarizes the current guidelines for selection of
      adolescent candidates for bariatric surgery and discusses the types of bariatric
      procedures presently available for this age group. Data on the complications and
      outcomes of bariatric surgery in this special population are reviewed.

PMID- 17030282
TI  - Current concepts in acne management.
AB  - Acne vulgaris is a nearly universal phenomenon among adolescents in the western
      world and continues to remain problematic for a significant proportion of adults.
      During adolescence, emotional and physical changes must be successfully
      integrated into the emerging sense of self, and skin disorders such as acne,
      which alter that self-image, may engender distressing feelings of embarrassment,
      shame, and disgust. While most patients eventually achieve spontaneous remission,
      approximately one quarter of teenagers will show evidence of permanent acne
      scarring by 18 years of age. This article reviews current information regarding
      the pathophysiology, clinical manifestations, differential diagnosis, and therapy
      of the adolescent patient who has acne, and emphasizes recent advances in acne
      management.

PMID- 17030283
TI  - Bone health in adolescents.
AB  - Adolescence is a crucial period for the accrual of bone density and achievement
      of peak bone mass. Unique situations can arise during adolescence that place an
      adolescent at risk for bone loss or the failure to attain appropriate bone mass.
      Clinicians also are challenged by the limitations of currently available
      measurement tools to evaluate skeletal status in young patients. This article
      reviews medical approaches to prevent bone loss in patients with eating disorders
      and the skeletal effects of specific hormonal contraceptive agents. Adolescent
      medicine specialists and gynecologists caring for teenagers must recognize the
      potential implications of these clinical settings on bone health to provide
      appropriate patient guidance and direct management.

PMID- 17030284
TI  - Advances in hormonal contraception.
AB  - This article presents a review of advances made in hormonal contraception over
      the past 15 years. It looks at the different routes of administration that have
      been developed, at newer formulations of conventional methods, and at novel
      contraceptive agents that are in the process of approval. The article provides a
      short description of each of these contraceptive methods, information about
      compliance, side effects, and efficacy, and an update on that particular method.

PMID- 17030285
TI  - Vaginal microbicides.
AB  - This article reviews the current status of microbicide development and challenges
      faced in developing safe and effective compounds. The ever growing HIV pandemic,
      lack of effective vaccines against HIV and other sexually transmitted infections,
      concern about the vulnerability of women, and difficulty in condom negotiation
      are factors that drive the development of topical microbicides as a prophylactic
      method for women. The ideal microbicide needs to be safe and highly effective and
      not increase viral resistance or cause disruption of host defenses. Advances in
      the understanding of HIV transmission and the role of other sexually transmitted
      infections have allowed progress in development of microbicide candidates as
      clinical trials of potential agents are awaited.

PMID- 17030286
TI  - Expedited partner therapy for adolescents diagnosed with gonorrhea or chlamydia:
      a review and commentary.
AB  - Management of sex partners is a cornerstone of sexually transmitted infection
      control in the United States. Face-to-face investigation and notification of
      exposure of sex partners by public health professionals seems to be the most
      effective method of ensuring appropriate partner management. However, resources
      rarely permit such intensive partner management for gonorrhea and chlamydial
      infection. Alternatives to public health-assisted notification and referral
      include expedited partner therapy, in which partners are treated before
      evaluation, most typically through patient-delivered therapy. Results from trials
      have shown generally favorable biomedical and behavioral outcomes. This article
      discusses the evidence for expedited partner therapy and its associated
      liability, confidentiality, financial, and administrative issues relating to
      adolescent patients and their health care providers.

PMID- 17030287
TI  - Tobacco use cessation for adolescents.
AB  - Adolescent tobacco users are unique. Thus far, effective interventions for adult
      tobacco users have been disappointing when applied to adolescents. This article
      reviews current evidence regarding adolescent tobacco use cessation
      interventions, explores under-researched areas in tobacco use cessation for
      adolescents, and offers assistance with treating adolescent tobacco users across
      the spectrum of use. A means of assessment and treatment of the adolescent smoker
      is proposed, and cases are included to assist the practitioner with treatment of
      the experimental tobacco user, the "adolescent-type" intermittent user, and the
      daily "adult-type" of adolescent tobacco user.

PMID- 17030288
TI  - Performance-enhancing drug use in young athletes.
AB  - This article explores the issue of performance-enhancing drug use in adolescent
      athletes. The article describes current substances that are being used by
      adolescent athletes, explains their positive and negative effects, examines
      factors contributing to their increased use in adolescent athletes, and discusses
      approaches to educating adolescents about alternate means of enhancing their
      athletic performance. It is hoped that this information will be useful toward
      encouraging young athletes to pursue, safe, healthy, and natural means of
      performance enhancement, such as practice and strength training, to improve
      sports performance in a safe, effective manner.

PMID- 17030289
TI  - Abuse of proprietary (over-the-counter) drugs.
AB  - A predominantly overlooked type of substance abuse by adolescents and young
      adults in the United States and around the world is the abuse of medications and
      other products sold without a prescription, or over-the-counter (OTC), to the
      public. OTC substance abuse causes significant morbidity and mortality, and there
      are concerns that some types of OTC substance abuse are increasing. Regular
      office screening for inhalant abuse and other substance abuse and health risk
      behaviors must be part of standard pediatric care. This article discusses what is
      known about the extent and clinical impact of OTC substance abuse and reviews key
      points about recognition, detection, and management.

PMID- 17030291
TI  - Asperger's syndrome.
AB  - Asperger's syndrome is a pervasive developmental disorder characterized by social
      impairments and rigid and repetitive interests or behaviors paired with
      relatively preserved cognitive and verbal facilities. This article describes the
      clinical manifestation of the disorder and guidelines for diagnostic assessment
      and intervention. Existing research is reviewed within the areas of epidemiology,
      medical/neurobiologic factors, genetics, and outcome, and future directions for
      research are recommended.

PMID- 17030290
TI  - Prescription drug misuse: a growing national problem.
AB  - Misuse of prescription drugs has been a growing problem in the United States
      affecting all age groups, including adolescents. Recent years have produced many
      advances in medical management of chronic pain, depression and anxiety, and
      attention-deficit/hyperactivity disorder. Many of the medications used to treat
      these disorders, such as the opioids, benzodiazepines, and psychostimulants, also
      have potential for abuse and dependence. The challenge for the clinician today is
      to maximize safe and effective treatment with available medication, while
      preventing the diversion of prescribed medication or the development of substance
      related disorders in patients receiving these medications.

PMID- 17030293
TI  - Enriching clinical knowledge.

PMID- 17030292
TI  - Adolescent psychopharmacology: drugs for mood disorders.
AB  - This article reviews mood disorders in children and adolescents, the diagnostic
      criteria, and important differential diagnoses to be considered. Critical points
      in the treatment of mood disorders and comorbid conditions and the important role
      the primary care provider can play in their management are stressed. Warning
      signs to identify adolescents who may be at risk of attempting suicide are
      discussed.

PMID- 17030294
TI  - Potential drug-herb interaction with antiplatelet/anticoagulant drugs.
AB  - This is a cross-sectional survey evaluating the use of herbal medicines in
      medical wards patients that may interfere with the effect of antiplatelet or
      anticoagulant therapy. Among the 250 patients participated, 42.4% (n=106) were
      taking herbs with 76 patients (71.7%) using herbs for the past 12 months.
      Overall, almost 31% (n=23, N=76) of patients were taking one or more of the
      specified herbal medicines [ginseng (Panax ginseng), garlic (Allium sativum),
      ginkgo (Gingko biloba) thought to interact with antiplatelet or anticoagulant
      therapy. The study showed that 21% (n=16, N=76) of patients co-ingested specified
      herbs with antiplatelet or anticoagulant therapy, of which half of them were at
      risk of potential drug-herb interactions. A large proportion of respondents
      involved in potential drug-herb interaction were elderly people (62.5%, n=5).
      However, more than 90% of herbal users did not disclose the use of herbal
      medicine to their health professionals. It is thus prudent for all care givers to
      be aware of the possibility of drug-herb interaction and inquire about herbal use
      from patients.

PMID- 17030295
TI  - Complementary and alternative medicine use in British Columbia--a survey of HIV
      positive people on antiretroviral therapy.
AB  - In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected
      final detailed data on complementary and alternative medicine (CAM) use in their
      HIV treatment program. This cross-sectional study of 682 participants examines
      types and determinants of CAM use in this program, and examines adverse effects
      associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM
      users in the included population, vitamins/minerals (81%), meditation/yoga (36%),
      massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines
      (19%), were most commonly used. Multivariate analysis indicated CAM users were
      less likely to have low education (AOR=0.51), more likely to be unemployed
      (AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to
      experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is
      common. Both patients and health professionals should be aware of potential
      toxicities and drug interactions related to the use of CAM and HIV/AIDS
      treatment.

PMID- 17030296
TI  - Auditing outcomes and costs of integrated complementary medicine provision--the
      importance of length of follow up.
AB  - A retrospective audit was carried out on 58 patients with chronic health problems
      who were referred by 22 general practitioners (GPs) for acupuncture,
      aromatherapy, homeopathy, massage and osteopathy, or a combination. Costs of GP
      consultations, prescriptions, secondary care referrals, and diagnostic tests from
      records of 33 of these patients were compared pre (24 months), during (mean 4.3
      months) and post (mean 5.7 months) complementary medicine (CM) treatment. Patient
      centred outcome data included the Measure Yourself Medical Outcome Profile
      (MYMOP) and content analysis of patient and practitioner comments. Costs of GP
      consultations/patient/month were significantly higher during (20.10 pounds,
      p<0.001) and post (17.53 pounds, p<0.01) CM treatment compared with pre-treatment
      costs (11.27 pounds). Total prescription costs were not significantly higher
      during and post-treatment than pre-treatment. Prescription costs for referred
      conditions were lower during (2.26 pounds) and higher post-treatment (3.75
      pounds) compared with costs pre-treatment (3.24 pounds). Pre- and post-treatment
      MYMOP scores indicated significant improvements in health and well-being. Longer
      follow up, is required in order to demonstrate significant cost savings related
      to CM provision. Cost comparisons with conventional medicine should consider
      quantitative and qualitative data to capture the wider benefits experienced by
      patients.

PMID- 17030297
TI  - Models of health: a survey of practitioners.
AB  - PURPOSE: Models of health influence providers' practice and delivery of health
      care. This study surveyed a random sample of providers to determine if health
      care providers from mainstream medicine (MM), integrative medicine (IM), and
      complementary and alternative medicine (CAM) hold mutually exclusive models of
      health or combine notions from models thought to be contradictory. METHODS: A
      survey was created through qualitative research, piloted, and mailed to a wide
      variety of MM, IM, and CAM health care professionals. RESULTS: All providers
      combined various models and definitions of health. Most utilized the biomedical
      approach to some extent. Balance (holistic model) and functioning in daily life
      were essential to most respondents' models of health, disease, and healing. Close
      communication between MM and CAM systems was preferred over complete separation
      or a single system. CONCLUSIONS: Many providers of all types combine widely
      disparate components in their definitions of health, providing keys for improving
      communication.

PMID- 17030298
TI  - The upside of cancer--a personal account of embracing life with cancer.
AB  - Carol Edmonston was first diagnosed with breast cancer in 1995. After a
      lumpectomy and 6 weeks of daily radiation therapy she continued living a full
      life. Exactly 2 years later she was diagnosed with an unrelated cancer in her
      other breast following a routine mammogram. She had a lumpectomy, along with
      lymph node dissection, followed by 6 weeks of daily radiation therapy. Upon
      completion, she took Tamoxifen for 5 years and is currently cancer free, enjoying
      a full and rich life. The following story offers a unique insight into one
      person's spiritual adventure through cancer and the personal transformation that
      followed using "Doodling" as a therapeutic tool.

PMID- 17030299
TI  - Prevalence surveys: to be taken with a pinch of salt.

PMID- 17030300
TI  - Kampo medicines as alternatives for treatment of migraine: six case studies.
AB  - Kampo is a well-recognized form of traditional medicine in Japan. This paper
      reports upon six cases of successful use of Kampo medicines, herbal medicine
      preparations, for the treatment of migraine. Most of the patients had been
      treated with conventional medicines, such as non-steroidal anti-inflammatory
      drugs or triptans, but were not satisfied with the outcomes of these conventional
      treatments with regard to their effectiveness or feelings of discomfort after
      administration. We administered two Kampo medicines, goshuyuto for prevention of
      migraine and senkyuchachosan as a painkiller. Both Kampo medicines worked
      successfully in the treatment of migraine and the patients were satisfied with
      their effects. Kampo medicine seems a favorable candidate for alternative therapy
      of migraine.

PMID- 17030301
TI  - Paving the way for complementary medicine?

PMID- 17030302
TI  - Implicit solvent models.
AB  - Implicit solvent models for biomolecular simulations are reviewed and their
      underlying statistical mechanical basis is discussed. The fundamental quantity
      that implicit models seek to approximate is the solute potential of mean force,
      which determines the statistical weight of solute conformations, and which is
      obtained by averaging over the solvent degrees of freedom. It is possible to
      express the total free energy as the reversible work performed in two successive
      steps. First, the solute is inserted in the solvent with zero atomic partial
      charges; second, the atomic partial charges of the solute are switched from zero
      to their full values. Consequently, the total solvation free energy corresponds
      to a sum of non-polar and electrostatic contributions. These two contributions
      are often approximated by simple geometrical models (such as solvent exposed area
      models) and by macroscopic continuum electrostatics, respectively. One powerful
      route is to approximate the average solvent density distribution around the
      solute, i.e. the solute-solvent density correlation functions, as in statistical
      mechanical integral equations. Recent progress with semi-analytical
      approximations makes continuum electrostatics treatments very efficient. Still
      more efficient are fully empirical, knowledge-based models, whose relation to
      explicit solvent treatments is not fully resolved, however. Continuum models that
      treat both solute and solvent as dielectric continua are also discussed, and the
      relation between the solute fluctuations and its macroscopic dielectric
      constant(s) clarified.

PMID- 17030303
TI  - Temperature dependence of the solubility of non-polar gases in water.
AB  - An explanation is provided for the experimentally observed temperature dependence
      of the solubility and the solubility minimum of non-polar gases in water. The
      influence of solute size and solute-water attractive interactions on the
      solubility minimum temperature is investigated. The transfer of a non-polar
      solute from the ideal gas into water is divided into two steps: formation of a
      cavity in water with the size and shape of the solute and insertion of the solute
      in this cavity which is equivalent to 'turning on' solute-water attractive
      interactions. This two step process divides the excess chemical potential of the
      non-polar solute in water into repulsive and attractive contributions,
      respectively. The reversible work for cavity formation is modeled using an
      information theory model of hydrophobic hydration. Attractive contributions are
      calculated by modeling the water structure in the vicinity of non-polar solutes.
      These models make a direct connection between microscopic quantities and
      macroscopic observables. Moreover, they provide an understanding of the peculiar
      temperature dependences of the hydration thermodynamics from properties of pure
      water; specifically, bulk water density and the water oxygen-oxygen radial
      distribution function.

PMID- 17030304
TI  - Towards a better description and understanding of biomolecular solvation.
AB  - We introduce a flexible framework for the correct description of the solvation of
      biological macromolecules, the dielectric field equation (DFE). The formalism
      permits the use of any combination of quantum mechanical (QM), molecular
      mechanical (MM) and continuum electrostatic (CE) based techniques. For the CE
      region a method that yields the electric field rather than the potential is
      outlined. The DFE formalism makes clear the need to consider and to calibrate a
      dielectric boundary region surrounding the simulation system. The details of how
      to do this are presented for the case of the Ewald summation method; the effects
      are demonstrated by calculations of the dielectric properties and the spatially
      resolved Kirkwood G-factor, G(K)(r), of TIP3P water. Computing the dielectric
      properties of a multi-component system provides a sensitive method to better
      understand the solvation of biological macromolecules. Towards this goal a
      rigorous analysis of the dielectric properties of solvated biomolecules based on
      a decomposition of the frequency-dependent dielectric constant (or
      susceptibility) of the full system is presented. The meaning of our approach is
      investigated, and the results of a first application are reported. Using the
      method of Voronoi polyhedra, the dielectric properties of the first two solvation
      shells and bulk water are compared by re-analyzing a 12-ns trajectory of a zinc
      finger peptide in water [Loffler et al. J. Mol. Biol. 270 (1997) 520]. It is
      found that the first shell behaves considerably different; in addition, there is
      a non-negligible contribution to the total susceptibility of the system from
      coupling between the protein and the bulk water phase, i.e. the water molecules
      not in the immediate vicinity of the solute.

PMID- 17030305
TI  - Optimized atomic radii for protein continuum electrostatics solvation forces.
AB  - Recently, we presented a Green's function approach for the calculation of
      analytic continuum electrostatic solvation forces based on numerical solutions of
      the finite-difference Poisson-Botzmann (FDPB) equation [Im et al., Comp. Phys.
      Comm. 111 (1998) 59]. In this treatment the analytic forces were explicitly
      defined as the first derivative of the FDPB continuum electrostatic free energy
      with respect to the coordinates of the solute atoms. A smooth intermediate region
      for the solute-solvent dielectric boundary needed to be introduced to avoid
      abrupt discontinuous variations in the solvation free energy and forces as a
      function of the atomic positions. In the present paper we extend the set of
      optimized radii, which was previously parametrized from molecular dynamics free
      energy simulations of the 20 standard amino acids with explicit solvent molecules
      [Nina et al., J. Phys. Chem. 101 (1997) 5239], to yield accurate solvation free
      energy by taking the influence of the smoothed dielectric region into account.

PMID- 17030306
TI  - Integral equation theories for predicting water structure around molecules.
AB  - Water plays a crucial role in the structure and function of proteins and other
      biological macromolecules; thus, theories of aqueous solvation for these
      molecules are of great importance. However, water is a complex solvent whose
      properties are still not completely understood. Statistical mechanical integral
      equation theories predict the density distribution of water molecules around a
      solute so that all particles are fully represented and thus potentially both
      molecular and macroscopic properties are included. Here we discuss how several
      theoretical tools we have developed have been integrated into an integral
      equation theory designed for globular macromolecular solutes such as proteins.
      Our approach predicts the three-dimensional spatial and orientational
      distribution of water molecules around a solute. Beginning with a three
      dimensional Ornstein-Zernike equation, a separation is made between a reference
      part dependent only on the spatial distribution of solvent and a perturbation
      part dependent also on the orientational distribution of solvent. The spatial
      part is treated at a molecular level by a modified hypernetted chain closure
      whereas the orientational part is treated as a Boltzmann prefactor using a quasi
      continuum theory we developed for solvation of simple ions. A potential energy
      function for water molecules is also needed and the sticky dipole models of
      water, such as our recently developed soft-sticky dipole (SSD) model, are ideal
      for the proposed separation. Moreover, SSD water is as good as or better than
      three point models typically used for simulations of biological macromolecules in
      structural, dielectric and dynamics properties and yet is seven times faster in
      Monte Carlo and four times faster in molecular dynamics simulations. Since our
      integral equation theory accurately predicts results from Monte Carlo simulations
      for solvation of a variety of test cases from a single water or ion to ice-like
      clusters and ion pairs, the application of this theory to biological
      macromolecules is promising.

PMID- 17030307
TI  - Description of hydration free energy density as a function of molecular physical
      properties.
AB  - A method to calculate the solvation free energy density (SFED) at any point in
      the cavity surface or solvent volume surrounding a solute is proposed. In the
      special case in which the solvent is water, the SFED is referred to as the
      hydration free energy density (HFED). The HFED is described as a function of some
      physical properties of the molecules. These properties are represented by simple
      basis functions. The hydration free energy of a solute was obtained by
      integrating the HFED over the solvent volume surrounding the solute, using a grid
      model. Of 34 basis functions that were introduced to describe the HFED, only six
      contribute significantly to the HFED. These functions are representations of the
      surface area and volume of the solute, of the polarization and dispersion of the
      solute, and of two types of electrostatic interactions between the solute and its
      environment. The HFED is described as a linear combination of these basis
      functions, evaluated by summing the interaction energy between each atom of the
      solute with a grid point in the solvent, where each grid point is a
      representation of a finite volume of the solvent. The linear combination
      coefficients were determined by minimizing the error between the calculated and
      experimental hydration free energies of 81 neutral organic molecules that have a
      variety of functional groups. The calculated hydration free energies agree well
      with the experimental results. The hydration free energy of any other solute
      molecule can then be calculated by summing the product of the linear combination
      coefficients and the basis functions for the solute.

PMID- 17030308
TI  - Application of a universal solvation model to nucleic acid bases: comparison of
      semiempirical molecular orbital theory, ab initio Hartree-Fock theory, and
      density functional theory.
AB  - The free energies of solvation of six nucleic acid bases (adenine, cytosine,
      hypoxanthine, guanine, thymine, and uracil) in water and chloroform are
      calculated using CM2 class IV charges and SM5.42R atomic surface tensions. Using
      any of three approximations to the electronic wave function (AM1, Hartree-Fock,
      or DFT), we obtain good agreement with experiment for five cases where the
      experimental results are known for the partition coefficients between the two
      solvents. Decomposition of the solvation effects into bulk electrostatic
      contributions and first-solvation-shell effects shows that the partitioning is
      dominated by the former, and this illustrates the importance of using accurate
      partial atomic charges for modeling these molecules in aqueous solution.

PMID- 17030309
TI  - Heat capacity and compactness of denatured proteins.
AB  - One of the striking results of protein thermodynamics is that the heat capacity
      change upon denaturation is large and positive. This change is generally ascribed
      to the exposure of non-polar groups to water on denaturation, in analogy to the
      large heat capacity change for the transfer of small non-polar molecules from
      hydrocarbons to water. Calculations of the heat capacity based on the exposed
      surface area of the completely unfolded denatured state give good agreement with
      experimental data. This result is difficult to reconcile with evidence that the
      heat denatured state in the absence of denaturants is reasonably compact. In this
      work, sample conformations for the denatured state of truncated CI2 are obtained
      by use of an effective energy function for proteins in solution. The energy
      function gives denatured conformations that are compact with radii of gyration
      that are slightly larger than that of the native state. The model is used to
      estimate the heat capacity, as well as that of the native state, at 300 and 350 K
      via finite enthalpy differences. The calculations show that the heat capacity of
      denaturation can have large positive contributions from non-covalent intraprotein
      interactions because these interactions change more with temperature in non
      native conformations than in the native state. Including this contribution, which
      has been neglected in empirical surface area models, leads to heat capacities of
      unfolding for compact denatured states that are consistent with the experimental
      heat capacity data. Estimates of the stability curve of CI2 made with the
      effective energy function support the present model.

PMID- 17030310
TI  - Calculation of short-range interactions between proteins.
AB  - Macromolecular association is an integral component of numerous cellular and
      technologically relevant processes. Most molecular theories of such association
      neglect the explicit solvent structure and rely on continuum concepts such as
      surface energies for calculating short-range interactions. We present a new such
      method for calculating the non-electrostatic component of the interaction-free
      energy, based on formalisms for calculating dispersion interactions between
      macromolecules. The interactions are separated into a short-ranged component that
      is treated atomistically, and a longer range component that is treated within the
      continuum Lifshitz-Hamaker approach. This description avoids the singularities
      inherent in the continuum dispersion formulation, and its effectiveness in
      characterizing the shape complementarity between interacting surfaces is shown to
      be comparable to that of surface area-based methods of similar parametric
      complexity. An advantage of the new method is that it allows facile calculation
      of the interaction free energy as a function of intermolecular separation,
      including steric effects; this makes it suitable for use in simulations of
      protein solutions.

PMID- 17030311
TI  - Electronic structure and biological activity of steroids.
AB  - We present the analysis of the electronic structure for 31 steroids by using HeI
      UV photoelectron spectroscopy (UPS) and MO calculations. The electronic structure
      of molecules in the gas phase is related directly to steroid-receptor binding
      measurements. The results indicate that formally 'inert' sigma-skeleton plays a
      crucial role in diversifying the electronic structures of the title compounds
      ('ribbon-orbital effect'). This is an attempt to rationalize the biological
      activity of steroids (represented through steroid-receptor binding) by making
      direct correlation between spectroscopic and biological data.

PMID- 17030312
TI  - Long-term molecular dynamics simulation of copper azurin: structure, dynamics and
      functionality.
AB  - A long-term molecular dynamics simulation (1.1 ns), at 300 K, of fully hydrated
      azurin has been performed to put into relationship the protein dynamics to
      functional properties with particular attention to those structural elements
      involved in the electron transfer process. A detailed analysis of the root mean
      square deviations and fluctuations and of the intraprotein H-bonding pattern has
      allowed us to demonstrate that a rigid arrangement of the beta-stranded protein
      skeleton is maintained during the simulation run, while a large mobility is
      registered in the solvent-exposed connecting regions (turns) and in the alpha
      helix. Moreover, the structural elements, likely involved in the electron
      transfer path, show a stable H-bonding arrangement and low fluctuations. Analysis
      of the dynamical cross-correlation map has revealed the existence of correlated
      motions among residues connected by hydrogen bonds and of correlated and anti
      correlated motions between regions which are supposed to be involved in the
      functional process, namely the hydrophobic patch and the regions close to the
      copper reaction center. The results are briefly discussed also in connection to
      the current through-bond tunneling model for the electron transfer process.
      Finally, a comparison with the structural and the dynamical behaviour of
      plastocyanin, whose structure and functional role are very similar to those of
      azurin, has been performed.

PMID- 17030313
TI  - Paramagnetic fluorescence quenching in a model membrane: a consideration of
      lifetime and temperature.
AB  - To expand our understanding of paramagnetic quenching in membranes, the
      relationship between fluorophore excited-state lifetime (tau), temperature, and
      the collisional quenching was studied. Specifically, the ability of tempo to
      quench the steady-state and time-resolved emission from five lipophilic
      fluorophores (diphenylhexatriene, perylene, phenanthrene, pyrene, and
      triphenylene) partitioned into egg phosphatidylcholine (EggPC) liposomes was
      examined. Also, the temperature dependence of spin-labeled androstane to quench
      the emission (steady-state and time-resolved) from perylene in EggPC liposomes
      was determined. Unexpectedly, in EggPC liposomes, the apparent quenching
      efficiency decreased with increasing tau until the effect leveled off above
      approximately 20 ns. Moreover, in EggPC liposomes, dynamic quenching decreased
      with increasing temperature. The results suggest that in membranes, paramagnetic
      quenching is more complex than generally recognized.

PMID- 17030314
TI  - Electrospray ionization mass spectrometry in the study of biomolecular non
      covalent interactions.
AB  - In the past mass spectrometry has been limited to the study of small, stable
      molecules, however, with the emergence of electrospray ionization mass
      spectrometry (ESI-MS) large biomolecules as well as non-covalent biomolecular
      complexes can be studied. ESI-MS has been used to study non-covalent interactions
      involving proteins with metals, ligands, peptides, oligonucleotides, as well as
      other proteins. Although complementary to other well-established techniques such
      as circular dichroism and fluorescence spectroscopy, ESI-MS offers some
      advantages in speed, sensitivity, and directness particularly in the
      determination of the stoichiometry of the complex. One major advantage is the
      ability of ESI-MS to provide multiple signals each arising from a distinct
      population within the sample. In this review I will discuss some of the different
      types of non-covalent biomolecular interactions that have been studied using ESI
      MS, highlighting examples which show the efficacy of using ESI-MS to probe the
      structure of biomolecular complexes.

PMID- 17030315
TI  - Structural and thermodynamic studies of KM+, a d-mannose binding lectin from
      Artocarpus integrifolia seeds.
AB  - The KM+ lectin exhibits a novel and unusual circular dichroism (CD) spectrum that
      could be explained by a high proline content that would be inducing deformation
      of the beta-structure and/or unusual turns. KM+ was shown to be a very rigid
      lectin, which was very stable under a broad variety of conditions (urea,
      guanidine, hydrolysis, pH, etc.). Only incubation for 60 min at 333-338 K and
      extreme basic pH were able to induce conformational changes which could be
      observed by CD and fluorescence measurements. Data from CD are typical for
      protein denaturing associated with changes in the overall secondary structure.
      Data from high-performance size exclusion chromatography (SEC) showed that the
      denatured forms produced at pH 12.0 are eluted in clusters that co-elute with the
      native forms. A significant contribution from the tyrosines to the fluorescence
      emission upon denaturation was observed above 328 K. In fact at 328 K some
      broadening of the emission spectrum takes place followed by the appearance of a
      shoulder (approx. 305 nm) at 333 K and above. The sensitivity of tryptophan
      fluorescence to the addition of sugar suggests a close proximity of the
      tryptophan residues to the sugar binding site, K(a)=(2.9+/-0.6)x10(3) M(-1). The
      fraction of chromophore accessible to the quencher obtained is f(a)=0.43+/-0.08,
      suggesting that approximately 50% of the tryptophan residues are not accessible
      to quenching by d-mannose. KM+ thermal denaturation was found to be irreversible
      and was analyzed using a two-state model (N-->D). The results obtained for the
      activation energy and transition temperature from the equilibrium CD studies
      were: activation energy, E(a)=134+/-11 kJ/mol and transition temperature,
      T(m)=339+/-1 K, and from the fluorescence data: E(a)=179+/-18 kJ/mol and
      T(m)=337+/-1 K. Kinetic studies gave the following values: E(a)=108+/-18 kJ/mol
      and E(a)=167+/-12 kJ/mol for CD and fluorescence data, respectively.

PMID- 17030316
TI  - Energetics of Ca(2+)-EDTA interactions: calorimetric study.
AB  - The interaction between Ca(2+) and EDTA has been studied using isothermal
      titration calorimetry to elucidate the detailed mechanism of complex formation
      and to relate the apparent thermodynamic parameters of calcium binding to the
      intrinsic effects of ionization. It has been shown that Ca(2+) binding to EDTA is
      an exothermic process in the temperature range 5-48 degrees C and is highly
      dependent on the buffer in which the reaction occurs. Calorimetric measurements
      along with pH-titration of EDTA under different solvent conditions shows that the
      apparent enthalpy effect of the binding is predominantly from the protonation of
      buffer. Subtraction of the ionization effect of buffer from the total enthalpy
      shows that the enthalpy of binding Ca(2+) to EDTA is -0.56 kcal mol(-1) at pH
      7.5. The DeltaH value strongly depends on solvent conditions as a result of the
      degree of ionization of the two amino groups in the EDTA molecule, but depends
      little on temperature, indicating that the heat capacity increment for metal
      binding is close to zero. At physiological pH values where the amino groups of
      EDTA with pK(a)=6.16 and pK(a)=10.26 are differently ionized, the coordination of
      the Ca(2+) ion into the complex leads to release of one proton due to
      deprotonation of the amino group having pK(a)=10.26. Increasing the pH up to
      11.2, where little or no ionization occurs, leads to elimination of the enthalpy
      component due to ionization, while its decrease to pH 2 leads to its increase,
      due to protonation of the two amino groups. The heat effect of Ca(2+)/EDTA
      interactions, excluding the deprotonation enthalpy of the amino groups, i.e. that
      associated with the intrinsic enthalpy of binding, is higher in value
      (Delta(b)H(o)=-5.4 kcal mol(-1)) than the apparent enthalpy of binding. Thus, the
      large DeltaG value for Ca(2+) binding to EDTA arises not only from favorable
      entropic but also enthalpic changes, depending on the ionization state of the
      amino groups involved in coordination of the calcium. This explains the great
      variability in DeltaH obtained in previous studies. The ionization enthalpy is
      always unfavorable, and therefore dramatically decreases Ca(2+) affinity by
      reduction of the enthalpy term of the stability function. The origin of the
      enthalpy and entropy terms in the stability of the Ca(2+)-EDTA complex is
      discussed.

PMID- 17030317
TI  - Complex patterns predicted in an in vitro experimental model system for the
      evolution of molecular cooperation.
AB  - An isothermal biochemical in vitro amplification system with two trans
      cooperatively coupled amplifying DNA molecules was investigated homogeneously
      using a hierarchy of kinetic models and as a simplified reaction-diffusion
      system. In our model of this recently developed experimental system, no reaction
      mechanism higher than second order occurs, yet numerical simulations show a
      variety of complex spatiotemporal patterns which arise in response to finite
      amplitude perturbations in a flow reactor. In a certain domain of the kinetic
      parameters the system shows self-replicating spots. These spots can stabilize the
      cooperative amplification in such evolving systems against emerging parasites.
      The results are of high relevance for experimental studies on these functional in
      vitro ecosystems in spatially resolved microstructured reactors.

PMID- 17030318
TI  - Effect of Na(+) concentration on the subgel phases of negatively charged
      phosphatidylglycerol.
AB  - The effect of Na(+) concentration on the subgel phase of
      dimyristoylphosphatidylglycerol (DMPG) was investigated by differential scanning
      calorimetry (DSC) and negative stain electron microscopy, and the results were
      compared with dipalmitoylphosphatidylglycerol (DPPG). The conversion mode of DMPG
      vesicle to the subgel phase by annealing at 5 degrees C was grouped into two
      types depending on whether Na(+) concentration is above or below 200-250 mM. For
      [Na(+)]>200-250 mM, the subgel phase of a crystalline superstructure of bilayers
      wrapped in a cylinder was attained during a 24-h period of annealing and
      transformed directly to the liquid crystal phase on heating. For [Na(+)]<200-250
      mM, two subgel phases which transform to the gel phase on heating were observed
      after annealing up to 24 h. Both subgel phases showed belt-like structures
      composed of loosely and closely stacked lamellae, respectively, and their
      fractions were found to depend on Na(+) concentration. With a further annealing
      up to 30 days, only the closely stacked subgel phase converted subsequently into
      the cylindrical superstructure of a more ordered phase. Similar two subgel phases
      were detected for DPPG at [Na(+)]< or =100 mM. The difference in the relative
      enthalpy between the gel and subgel phases was investigated from the van der
      Waals interaction energy between the hydrocarbon chains.

PMID- 17030319
TI  - A fluorescence study of the molecular interactions of harmane with the
      nucleobases, their nucleosides and mononucleotides.
AB  - Fluorescence binding studies of harmane to the elemental components of the
      nucleic acids were undertaken to investigate the origin of the interaction
      between the drug and DNA. Most of the tested substrates have been found to induce
      hypochromism in the absorption spectrum of harmane and to quench its
      fluorescence. The quenching process induced by the nucleobases and their
      nucleosides is mainly due to the formation of ground state 1:1 complexes.
      However, in the case of the mononucleotides a dynamic quenching component is also
      observed. This quenching component is likely due to the excited state interaction
      of harmane with the phosphate group of the nucleotides. UV-vis spectral changes
      and quenching measurements have been used to quantify the ground state
      association constants of the complexes and the quenching rate constants.

PMID- 17030320
TI  - Free radical scavenging ability and antioxidant efficiency of curcumin and its
      substituted analogue.
AB  - Free radical reactions of curcumin and its ethoxy substituted derivative (C1) 1,7
      bis-(4-hydroxy-3-ethoxy phenyl)-1,6-heptadiene-3,5-dione have been studied using
      a pulse radiolysis technique in homogeneous aqueous-organic solutions like
      acetonitrile-water and isopropanol-water mixtures, as well as in neutral TX-100
      and cationic CTAB micellar solutions. The phenoxyl radicals of curcumin or C1
      were generated by one-electron transfer to several oxidants like N(3)(.), Br(2)(
      .), CCl(3)O(2)(.), glutathione radicals which exhibit absorption from a 300-600
      nm wavelength region with the maximum at 490-500 nm. Other important properties
      of the phenoxyl radicals such as extinction coefficient, radical lifetime and
      their formation and decay rate constants were also determined in these systems.
      The antioxidant property of curcumin and C1 were estimated in terms of their
      ability to inhibit the lipid peroxidation in liposomes and also in terms of
      trolox equivalent antioxidant capacity (TEAC). The results were compared with
      alpha-tocopherol.

PMID- 17030321
TI  - Inverted hexagonal and cubic phases induced by alpha-tocopherol in fully hydrated
      dispersions of dilauroylphosphatidylethanolamine.
AB  - The effect of alpha-tocopherol on the thermotropic phase behaviour and structure
      of aqueous dispersions of 1,2-di-lauryl-sn-glycero-3-phosphoethanolamine was
      examined by synchrotron X-ray diffraction. The pure phospholipid exhibited a
      lamellar gel to liquid-crystal phase transition at 30 degrees C on heating at 3
      degrees C min(-1) between 10 degrees C and 90 degrees C. The transition was
      reversible with a temperature hysteresis of 0.3 degrees C on cooling. At
      temperatures less than 10 degrees C only lamellar gel phase of the pure
      phospholipid was seen in co-dispersions of up to 20 mol % alpha-tocopherol. The
      presence of 2.5 mol % alpha-tocopherol caused the appearance of inverted
      hexagonal phase at temperatures just below the main phase transition temperature
      that co-existed with the lamellar gel phase. The intensity of scattering from the
      hexagonal-II phase increased with increasing proportion of alpha-tocopherol in
      the mixture and in proportions greater than 10 mol % it persisted at temperatures
      above the main transition and co-existed with the lamellar liquid-crystal phase
      of the pure phospholipid. At higher temperatures all co-dispersions containing up
      to 15 mol % alpha-tocopherol showed the presence of cubic phases. These phases
      indexed a Pn3m or Pn3 space grouping. When the proportion of alpha-tocopherol was
      increased to 20 mol % the only non-lamellar phase observed was inverted hexagonal
      phase. This phase co-existed with lamellar gel and liquid-crystal phases of the
      pure phospholipid, but was the only phase present at temperatures >60 degrees C.
      The X-ray diffraction data were used to construct a partial phase diagram of the
      lipid mixture in excess water between 10 degrees and 90 degrees C and up to 20
      mol % alpha-tocopherol in phospholipid.

PMID- 17030322
TI  - A statistical mechanical theory for the adsorption of protein to liposomal
      membranes.
AB  - The observed topology change of spherical lipid vesicles to coffee cups [Saitoh,
      A. et al., Proc. Natl. Acad. Sci. USA 95 (1998) 1026] was analyzed by a
      statistical mechanical theory. The topology change was due to the adsorption of
      talin molecules to the orifices of the coffee cups. The adsorption isotherm of
      talin between an aqueous solution and the vesicle membrane was analyzed by taking
      account of the bending energy of the membrane. The equilibrium is determined by
      the balance of the energy gain for the adsorption of talin to the periphery of
      the vesicles and the change of the bending energy of the membrane due to the
      shape change. The observed coexistence of coffee cups and sheet-like vesicles
      were reproduced. Vesicles with two orifices were also analyzed and theoretically
      reproduced.

PMID- 17030323
TI  - Elastic control of electron transfer enthalpy and intensity of light absorption
      by cupric blue proteins.
AB  - The experimental data available shows that the change in enthalpy accompanying
      electron transfer to cupric blue proteins decreases as the ratio of the strengths
      of two visible light absorption bands increases. A compact mathematical
      expression for this inverse relation is formulated, the derivation of which
      demonstrates that the unusual geometry imposed by the protein upon the redox site
      is responsible both for the optical band intensity ratio and for a significant
      fraction of the enthalpy change.

PMID- 17030324
TI  - Effect of aminophospholipid glycation on order parameter and hydration of
      phospholipid bilayer.
AB  - The effect of aminophospholipid glycation on lipid order and lipid bilayer
      hydration was investigated using time-resolved fluorescence spectroscopy. The
      changes of lipid bilayer hydration were estimated both from its effect on the
      fluorescence lifetime of The 1-[4-(trimethylammonium)-phenyl]-6-phenylhexa-1,3,5
      triene (TMA-DPH) and 1,6-diphenylhexa-1,3,5-triene (DPH) and using solvatochromic
      shift studies with 1-anilinonaphthalene-8-sulfonic acid. The head-group and acyl
      chain order were determined from time-resolved fluorescence anisotropy
      measurements of the TMA-DPH and DPH. The suspensions of small unilamellar
      vesicles (with phosphatidylethanolamine/phosphatidylcholine molar ratio 1:2.33)
      were incubated with glyceraldehyde and it was found that aminophospholipids react
      with glyceraldehyde to form products with the absorbance and the fluorescence
      properties typical for protein advanced glycation end products. The lipid
      glycation was accompanied by the progressive oxidative modification of
      unsaturated fatty acid residues. It was found that aminophospholipid glycation
      increased the head-group hydration and lipid order in both regions of the
      membrane. The lipid oxidation accompanying the lipid glycation affected mainly
      the lipid order, while the effect on the lipid hydration was small. The increase
      in the lipid order was presumably the result of two effects: (1) the modification
      of head-groups of phosphatidylethanolamine by glycation; and (2) the degradation
      of unsaturated fatty acid residues by oxidation.

PMID- 17030325
TI  - Partial molar volumes of some alpha-amino acids in aqueous sodium acetate
      solutions at 308.15 K.
AB  - The apparent molar volumes V(2,phi) have been determined for glycine, DL-alpha
      alanine, DL-alpha-amino-n-butyric acid, DL-valine and DL-leucine in aqueous
      solutions of 0.5, 1.0, 1.5 and 2.0 mol kg(-1) sodium acetate by density
      measurements at 308.15 K. These data have been used to derive the infinite
      dilution apparent molar volumes V(0)(2,phi) for the amino acids in aqueous sodium
      acetate solutions and the standard volumes of transfer, Delta(t)V(0), of the
      amino acids from water to aqueous sodium acetate solutions. It has been observed
      that both V(0)(2,phi) and Delta(t)V(0) vary linearly with increasing number of
      carbon atoms in the alkyl chain of the amino acids. These linear correlations
      have been utilized to estimate the contributions of the charged end groups
      (NH(3)(+), COO(-)), CH(2) group and other alkyl chains of the amino acids to
      V(0)(2,phi) and Delta(t)V(0). The results show that V(0)(2,phi) values for
      (NH(3)(+), COO(-)) groups increase with sodium acetate concentration, and those
      for CH(2) are almost constant over the studied sodium acetate concentration
      range. The transfer volume increases and the hydration number of the amino acids
      decreases with increasing electrolyte concentrations. These facts indicate that
      strong interactions occur between the ions of sodium acetate and the charged
      centers of the amino acids. The volumetric interaction parameters of the amino
      acids with sodium acetate were calculated in water. The pair interaction
      parameters are found to be positive and decreased with increasing alkyl chain
      length of the amino acids, suggesting that sodium acetate has a stronger
      dehydration effect on amino acids which have longer hydrophobic alkyl chains.
      These phenomena are discussed by means of the co-sphere overlap model.

PMID- 17030327
TI  - Analysis of fibrous network fluid permeation data using the theory of
      ultracentrifugation: application to fibrin gels.
AB  - A new and alternative method for calculating the strand diameter of fibrous gel
      networks from fluid permeation data is developed and used to analyze and compare
      previous Darcy constant measurements of fibrin gels. The calculated diameters
      from the various sets of experimental data using this method gives for a coarse
      fibrin clot a strand diameter of approximately 1000 A and for a fine fibrin clot
      a strand diameter of 170 A.

PMID- 17030326
TI  - Conformational spectra--probing protein conformational changes.
AB  - Stafford [Biophys. J. 17 (1996) MP452] has shown that it is possible, using the
      analytical ultracentrifuge in sedimentation velocity mode, to calculate the
      molecular weights of proteins with a precision of approximately 5%, by fitting
      Gaussian distributions to g(s*) profiles so long as partial specific volume and
      the radial position of the meniscus are known. This makes possible the analysis
      of systems containing several components by the fitting of multiple distributions
      to the total g(s*) profile. We have found the Stafford relationship to hold for a
      range of protein solutes, particularly good agreement being found when the g(s*)
      profiles are computed from Schlieren (dc/dr vs. r) data using the Bridgman
      equation [J. Am. Chem. Soc. 64 (1942) 2349] . On this basis, we have developed a
      new approach to the analysis of systems where two or more distinguishable
      conformations of a single species are present, either in the same sample cell or
      in different cells in the same rotor. In the former case, this allows us to
      analyse a given solution of pure protein (i.e. monodisperse with respect to M) to
      reveal the presence in that solution of two or more conformers under identical
      solvent conditions. In the latter case, we can detect with high sensitivity any
      conformational change occurring in the transition from one set of solvent
      conditions to another. Alternatively, in this case, we can analyse slightly
      different proteins (e.g. deletion mutants) for conformational changes under
      identical solvent conditions. Examples of these procedures using well-defined
      protein systems are given.

PMID- 17030328
TI  - Ligand binding on ladder lattices.
AB  - The ligand binding problems on two-dimensional ladders, which model many
      important binding phenomena in molecular biology, are studied in details. The
      model is represented by four parameters, the interactions between ligands when
      bound to adjacent sites on opposite legs of the ladder (tau), the interactions
      between bound ligands in the longitudinal direction of the ladder (sigma), the
      number of binding sites that are covered by a bound ligand (m), and the intrinsic
      binding constant (K). The partition functions of ring ladders are approached with
      the transfer matrix method. A general relation is derived which connects the
      partition function of a linear ladder with that of a ring ladder. The results
      obtained apply to the general situation of multivalent binding, in which m>1.
      Special attention is paid to the case where the ligand covers one site (m=1). In
      this case explicit formulas are given for the partition functions of ring and
      linear ladders. Closed-form expressions are obtained for various properties of
      the system, including the degree of binding (theta), the midpoint in the binding
      isotherm (1/square root(tau sigma)), the initial and end slopes of the Scatchard
      plots (2sigma + tau - 4 and -sigma2 tau, respectively). From these closed-form
      formulas, sigma and tau may be extracted from experimental data. The model
      reveals certain features which do not exist in one-dimensional models. Using the
      general method discussed in [1], the recurrence relation is found for the
      partition functions. The analytical solution found for this model provides test
      cases to verify the numerical results for more complex two-dimensional models.

PMID- 17030329
TI  - Effects of alcohols on lipid bilayers with and without cholesterol: the
      dipalmitoylphosphatidylcholine system.
AB  - Differential scanning calorimetry is a useful method to study the thermotropic
      phase transitions of a phospholipid bilayer. In the present study DSC is used to
      determine the effects of methanol and ethanol on DPPC and DPPC/2 mol% cholesterol
      bilayers. The biphasic effect of the main transition and the presence of an extra
      peak on the DSC cooling scans were observed above certain alcohol concentrations.
      In the presence of 2% cholesterol, the concentration at which the biphasic effect
      occurs is increased by both short-chain alcohols. 1,6-Diphenyl-1,3,5-hexatriene
      (DPH) is used as a fluorescent probe to directly determine the onset of
      interdigitation in these systems as reflected by a drop in the DPH fluorescence
      intensity.

PMID- 17030330
TI  - Conformation of poly(methacrylic acid) in acidic aqueous solution studied by
      small angle X-ray scattering.
AB  - The nature of the contracted form of poly(methacrylic acid) PMA chain in salt
      free acidic aqueous solution was studied by analyzing scattering curves
      registered by small-angle X-ray scattering, comparing it with those of PMA in
      methanol at 26 degrees C and of partially neutralized PMA in aqueous solution
      containing added salt (the concentration of added salt, Cs=0.1 M NaF). It is
      shown that the distribution of segments in the contracted form as well as that of
      PMA in methanol is that of a random-coil in a theta medium and that this
      distribution of segments is stable over a fair range of degrees of ionization
      alpha for Cs below 0.1 M. Moreover, the persistence length of PMA at Cs=0.1 M
      (4+/-0.5 A) is substantially constant throughout the entire range of alpha,
      indicating that the contracted form of PMA changes to an expanded random-coil in
      a higher pH region without a significant change in the chain flexibility.

PMID- 17030331
TI  - The role of conformational energetic disorder in the catalytic activity of
      immobilized enzymes.
AB  - We analyze cooperative behavior in a system of immobilized enzymes which
      incorporates the notion of heterogeneity or disorder in the interactions. In
      addition to equilibrium phase changes, this system exhibits vitrification or
      glass-like transitions in which the overall catalytic activity freezes into one
      of many possible states. It is shown that these long-lived metastable phases can
      be produced by a combination of disorder, systematic surface and intermolecular
      interactions, and chemical association effects such as ligand binding.
      Biophysical consequences of this frozen state include greatly diminished
      sensitivity of enzymatic activity to thermal and chemical perturbations. This
      effect coincides with the appearance of a multitude of possible macroscopic
      catalytic states rather than a single equilibrium state. Our analysis also
      suggests that high surface coverages will tend to be catalytically inactive if
      they are fully equilibrated; rather, high activity with high surface coverage is
      more likely to be associated with vitrified states of surface immobilization and
      deep or abrupt chemical quenches.

PMID- 17030332
TI  - Physico-chemical aspects of the interaction between DNA and oppositely charged
      mixed liposomes.
AB  - The mechanism of complex formation between DNA and oppositely charged
      dioctadecyldimethylammonium bromide/dioleoyl phosphatidylethanolamine
      (DODAB/DOPE) and 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)/DOPE mixed
      liposomes, as well as the physico-chemical properties of DNA-mixed liposome
      complexes, were examined. Fluorescence microscopy showed that the interaction
      between DNA and oppositely charged mixed liposomes started at very low liposome
      concentrations and induced a discrete coil-globule transition in individual DNA
      molecules. The DNA size distribution was bimodal in a wide range of liposome
      concentrations. The critical concentration of the cationic lipid needed for the
      complete compaction of single DNA molecules depended on the composition of the
      charged mixed DODAB/DOPE and DOTAP/DOPE liposomes. Cryogenic transmission
      electron microscopy (cryo-TEM) observations of DNA complexes with mixed liposomes
      revealed that the lamellar packing of lipid molecules was typical for the
      complexes formed from the cationic lipid-enriched mixtures, while inverted
      hexagonal arrays were found for the neutral lipid-enriched complexes. The
      microstructures of the complexes were also examined with the use of the small
      angle X-ray scattering (SAXS) technique, which confirmed the results obtained by
      cryo-TE microscopy and enabled the quantitative characterization of lipid
      packaging in the complexes with DNA macromolecules. We also found that the
      introduction of the neutral lipid into the complexes between DNA and oppositely
      charged lipids, DODAB and DOTAP, moderately increased the thermal stability of
      the complexes and changed the quantitative characteristics of the melting
      profiles of the complexes.

PMID- 17030333
TI  - Hydrophobic thickness of fluid planar monooleylglycerol membranes maximally
      thinned by inversed micellisation.
AB  - A procedure of making membranes of amphiphilic materials at the bottom of a U
      shaped flexible plastic tube within an aqueous medium is described. The membranes
      were made sufficiently large in order for the annulus area to be neglected.
      Consequently the hydrophobic thickness of the membrane could be measured by a
      capacitance technique assuming the relative permittivity of the hydrophobic part
      of the bilayer. Introduction of an AC microvolt technique allowed manufacture of
      stable thick membranes by quenching the electroconstriction observed when DC
      electrical potentials in the millivolt range are used. By continuously monitoring
      the hydrophobic thickness and by use of the AC microvolt technique the membrane
      thinning process by chemical means could be studied in isolation because the
      electroconstriction was quenched. The maximally thinned hydrophobic thickness of
      a monooleylglycerol membrane measured at 38 degrees C was found to be 25+/-1.2 A.
      Criteria and argumentation for maximal thinning of the membrane are put forward.
      A distinction between genuine and modified cholesterol was demonstrated to be
      possible by the described method.

PMID- 17030334
TI  - Effects of solvents interacting favorably with hydrophilic segments of the
      membrane surface of phosphatidylcholine on their gel-phase membranes in water.
AB  - We have investigated the effects of two kinds of solvents forming the lamellar
      liquid-crystalline (L(alpha)) phase in phosphatidylcholine (PC) membranes in neat
      condition, such as formamide and 1,3-propanediol, on phase behaviors of
      multilamellar vesicle (MLV) of DPPC (DPPC-MLV). These solvents induced the
      interdigitated gel (L(beta)I) phase in DPPC-MLV in excess water above their
      critical concentrations. Solubility measurement indicates that these solvents
      interact favorably with the hydrophilic segment of the PC membrane but interact
      unfavorably with the alkyl chains. Based on these results, we propose the
      mechanism of the induction of the L(beta)I phase by these solvents.

PMID- 17030335
TI  - Molecular dynamics simulations of Cu,Zn superoxide dismutase: effect of
      temperature on dimer asymmetry.
AB  - Molecular dynamics simulations of solvated dimeric Cu,Zn superoxide dismutase
      have been carried out at four temperatures, namely 200, 225, 250 and 300 K.
      Analysis of the backbone-to-backbone hydrogen bonds number indicates that the
      symmetry observed in the two subunits at 200 K is gradually lost by heating the
      system. The C(alpha) atoms displacement cross-correlation maps confirm that the
      asymmetric behaviour of the two subunits increases as a function of temperature.
      The dynamic cross-correlation of the subunits volumes indicates a fast
      correlation between the two subunits at 300 K, which is delayed upon lowering the
      simulation temperature. These results indicate that temperature plays an
      essential role in injecting such an asymmetry; the two subunits being asymmetric
      and in rapid communication at 300 K, and almost symmetric and in slow
      communication at lower temperatures.

PMID- 17030336
TI  - RNA switches the higher-order structure of DNA.
AB  - By the direct observation of single duplex DNA molecules by fluorescence
      microscopy, we found that RNA molecules have the potential to change discretely
      the higher-order structure of individual DNA molecules between the compact and
      elongated states. We performed an experiment with a linear giant DNA (T4 DNA, 166
      kbp) and a circular DNA (cosmid vector, 42 kbp), and examined the effect of
      single-strand RNA on their conformations under a physiological concentration of
      spermidine. Individual DNA chains compacted by spermidine were elongated in an
      abrupt manner with an increase in the RNA concentration. This finding is
      discussed in view of the effect of the interplay between the dynamics of
      chromosomal DNA and the production of RNA in the cytoplasmic environment.

PMID- 17030337
TI  - A molecular dynamics simulation study of the solvent isotope effect on copper
      plastocyanin.
AB  - The effect of heavy water on the structure and dynamics of copper plastocyanin as
      well as on some aspects of the solvent dynamics at the protein-solvent
      interfacial region have been investigated by molecular dynamics simulation. The
      simulated system has been analyzed in terms of the atomic root mean square
      deviation and fluctuations, intraprotein H-bond pattern, dynamical cross
      correlation map and the results have been compared with those previously obtained
      for plastocyanin in H2O (Ciocchetti et al. Biophys. Chem. 69 (1997), 185-198).
      The simulated plastocyanin structure in the two solvents, averaging 1 ns, is very
      similar along the beta-structure regions, while the most significant differences
      are registered, analogous to the turns and the regions likely involved in the
      electron transfer pathway. Moreover, plastocyanin in D2O shows an increase in the
      number of both the intraprotein H-bonds and the residues involved in correlated
      motions. An analysis of the protein-solvent coupling evidenced that D2O makes the
      H-bond formation more difficult with the solvent molecules for positively charged
      and polar residues, while an opposite trend is observed for negatively charged
      residues. On the other hand, the frequency of exchange of the solvent molecules
      involved in the protein-solvent H-bond formation is significantly depressed in
      D2O. The results are discussed also in connection with protein functionality and
      briefly with some experimental results connected with the thermostability of
      proteins in D2O.

PMID- 17030338
TI  - Modulation of cellular rhythm and photoavoidance by oscillatory irradiation in
      the Physarum plasmodium.
AB  - We studied responses of cellular rhythm and light-induced movement to periodic
      irradiation in a unicellular amoeboid organism, the Physarum plasmodium. The
      intrinsic frequency of the contraction rhythm, which is based on biochemical
      oscillations, became synchronized with the frequency of periodic irradiation with
      light when both frequencies were close enough. In order to study the role of the
      synchronization in light-induced movement, periodic irradiation was applied to
      only part of the plasmodium. The rate of avoidance of light was modulated in the
      frequency band in which the synchronization occurred. The synchronization
      property of the contraction oscillation underlies the regulation of tactic
      movement in plasmodium.

PMID- 17030339
TI  - Partial molar volumes of proteins: amino acid side-chain contributions derived
      from the partial molar volumes of some tripeptides over the temperature range 10
      90 degrees C.
AB  - The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is
      one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine,
      histidine, cysteine, proline, glutamic acid, and arginine, have been determined
      in aqueous solution over the temperature range 10-90 degrees C using differential
      scanning densitometry . These data, together with those reported previously, have
      been used to derive the partial molar volumes of the side-chains of all 20 amino
      acids. The side-chain volumes are critically compared with literature values
      derived using partial molar volumes for alternative model compounds. The new
      amino acid side-chain volumes, along with that for the backbone glycyl group,
      were used to calculate the partial specific volumes of several proteins in
      aqueous solution. The results obtained are compared with those observed
      experimentally. The new side-chain volumes have also been used to re-determine
      residue volume changes upon protein folding.

PMID- 17030340
TI  - Hydrophobicity of benzene.
AB  - The present work tries to clarify the molecular origin of the poor solubility of
      benzene in water. The transfer of benzene from pure liquid phase into water is
      dissected in two processes: transfer from gas phase to pure liquid benzene; and
      transfer from gas phase to liquid water. The two solvation processes are analyzed
      in the temperature range 5-100 degrees C according to Lee's Theory. The solvation
      Gibbs energy change is determined by the balance between the work of cavity
      creation in the solvent, and the dispersive interactions of the inserted benzene
      molecule with the surrounding solvent molecules. The purely structural solvent
      reorganization upon solute insertion proves to be a compensating process. The
      analysis shows that the work of cavity creation is larger in water than in
      benzene, whereas the attractive energetic interactions are stronger in benzene
      than in water; this scenario is true at any temperature. Therefore, both terms
      act in the same direction, contrasting the transfer of benzene from pure liquid
      phase into water and determining its hydrophobicity.

PMID- 17030342
TI  - Two-dimensional receptor patterns in the plasma membrane of cells. A critical
      evaluation of their identification, origin and information content.
AB  - A concise review is presented on the nature, possible origin and functional
      significance of cell surface receptor patterns in the plasma membrane of lymphoid
      cells. A special emphasize has been laid on the available methodological
      approaches, their individual virtues and sources of errors. Fluorescence energy
      transfer is one of the oldest available means for studying non-randomized co
      distribution patterns of cell surface receptors. A detailed and critical
      description is given on the generation of two-dimensional cell surface receptor
      patterns based on pair-wise energy transfer measurements. A second hierarchical
      level of receptor clusters have been described by electron and scanning force
      microscopies after immuno-gold-labeling of distinct receptor kinds. The origin of
      these receptor islands at a nanometer scale and island groups at a higher
      hierarchical (mum) level, has been explained mostly by detergent insoluble
      glycolipid-enriched complexes known as rafts, or detergent insoluble glycolipids
      (DIGs). These rafts are the most-likely organizational forces behind at least
      some kind of receptor clustering [K. Simons et al., Nature 387 (1997) 569]. These
      models, which have great significance in trans-membrane signaling and intra
      membrane and intracellular trafficking, are accentuating the necessity to revisit
      the Singer-Nicolson fluid mosaic membrane model and substitute the free protein
      diffusion with a restricted diffusion concept [S.J. Singer et al., Science 175
      (1972) 720].

PMID- 17030343
TI  - Fluorescence correlation spectroscopy analysis of the hydrophobic interactions of
      protein 4.1 with phosphatidyl serine liposomes.
AB  - Fluorescence correlation spectroscopy (FCS) was applied to examine the
      interactions between a protein and a membrane lipid. The protein 4.1-phosphatidyl
      serine (PS) interactions served as the model system to demonstrate the membrane
      lipid-protein interactions. This protein was labeled with rhodamine and its
      interactions with PS-liposomes were measured by FCS. The present results clearly
      demonstrated that a small protein molecule, protein 4.1, interacts specifically
      with a large particle, a PS-liposome. This interaction appears to be hydrophobic
      and not electrostatic, since the bound protein 4.1 did not dissociate in solution
      and was specifically released from PS-liposomes by treatment with phospholipase
      A(2) (PLA(2)). In the present study, using FCS we could demonstrate that the
      serine residue of PS is required for protein 4.1 to bind to PS-liposomes and that
      the bound protein 4.1 is closely associated with the fatty acid of the PS
      molecule in the liposomes.

PMID- 17030344
TI  - Regulation of the ryanodine receptor calcium release channel: a molecular complex
      system.
AB  - Skeletal muscle contraction is regulated by Ca(2+) released from the sarcoplasmic
      reticulum (SR). The Ca(2+) release channel in the SR has been identified as the
      ryanodine receptor (RyR). Recently, it was found that the RyR is a large
      transmembrane protein that is regulated by many intrinsic factors. In this
      review, we mainly summarize our experimental results. We will first show that
      calsequestrin and the DIDS-binding 30-kDa protein work as intrinsic factors and
      regulate the RyR Ca(2+) release channel. Next, the DIDS-binding 30-kDa protein
      was identified as the ADT/ATP translocase (AAT) present in mitochondria, based on
      a cDNA analysis. This result shows that AAT is bifunctional and works as a
      transporter protein in mitochondria and as a regulator of Ca(2+) release in the
      SR. From these results, we propose a model in which calsequestrin, the DIDS
      binding 30-kDa protein, and junctin form a ternary complex that regulates the RyR
      Ca(2+) release channel through interactions with triadin.

PMID- 17030345
TI  - Accelerated diffusion of Na(+) in a hydrophobic region revealed by molecular
      dynamics simulations of a synthetic ion channel.
AB  - To get insight into the significance of the hydrophobic lining on the ion
      permeation, we performed molecular dynamics simulations on a Na(+) permeation
      through a de novo synthetic hydrophobic channel. Electrophysiological study has
      suggested that the channel is formed from a tail-to-tail associated dimer of a
      cyclic octa-peptide coupled with hydrophobic acyl chains. The acyl chains line
      the channel pore while the cyclic peptide forms the channel entrance [Z. Qi, M.
      Sokabe, K. Donowaki, H. Ishida, Biophys. J. 76 (1999) 631]. Molecular dynamics
      simulation of water in the channel indicated that the inferred structure is
      physically reasonable [Z. Qi, M. Sokabe, Biophys. Chem. 71 (1998) 35]. In the
      present study, the potential energy profile of the Na(+) and the energy
      contributions from each component of the system at different positions along the
      channel axis were calculated. An energy well instead of a peak is located at the
      central hydrophobic cavity of the channel, due to its ability of accommodating at
      least five water molecules to hydrate the ion. Interestingly, the ion diffuses
      much faster in the hydrophobic acyl chain region, particularly in the central
      hydrophobic cavity, than it does in the peptide ring region and even surprisingly
      faster than that in the bulk phase. These results provide a physical basis for an
      idea that the hydrophobic lining of the K(+) channel [D.A. Doyle, J.M. Cabral,
      R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon,
      Science 280 (1998) 69] plays an active role to facilitate the ion permeation
      through the channel pore.

PMID- 17030346
TI  - Quantitative Western blot analysis of plasma ADAMTS13 antigen in patients with
      Upshaw-Schulman syndrome.

PMID- 17030347
TI  - Hypertension in cardiopulmonary bypass: a sign of insufficient anticoagulation in
      a patient undergoing surgical resection of myxoma.

PMID- 17030348
TI  - Vertical migration studies of 137Cs from nuclear weapons fallout and the
      Chernobyl accident.
AB  - The vertical migration of (137)Cs originating from nuclear weapons fallout (NWF)
      and the Chernobyl accident has been studied at 33 sampling sites in western
      Sweden. An attempt to describe the present depth distribution with a solution to
      the convection-diffusion equation (CDE) with a pulse-like fallout event as the
      initial condition was made. A sum of two CDEs describing the NWF and Chernobyl
      debris was fitted to the actual depth profiles measured by soil sampling. The
      fitted depth profiles were used to correct in situ measurements for the actual
      depth distribution, showing good agreement with the accumulated activities in
      soil samples. As expected, the vertical migration was very slow and most caesium
      was still present in the upper soil layers. The ranges of the apparent convection
      velocity, v, and apparent diffusion coefficient, D, were between 0 and 0.35
      cm/year and 0.06 and 2.63 cm(2)/year, respectively.

PMID- 17030349
TI  - L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in
      ovarian carcinoma cells.
AB  - OBJECTIVE: Apoptosis resistance is a hallmark of cancer progression, a phenomenon
      frequently observed in ovarian carcinoma. We reported previously, that L1
      adhesion molecule (CD171) is overexpressed in ovarian and endometrial carcinomas
      and that L1 expression is a predictor of poor outcome. We investigated a possible
      role of L1 in apoptosis resistance. METHODS: We used L1 transfectants and ovarian
      carcinoma cell lines and induced apoptosis by different stimuli such as C2
      ceramide, staurosporine, cisplatin or hypoxia. RESULTS: We found that cells
      expressing L1 are more resistant against apoptosis. In HEK293 cells, L1
      expresssion leads to a sustained ERK, FAK and PAK phosphorylation. Soluble L1
      only partially rescued HEK293 cells from apoptosis. Treatment with apoptotic
      stimuli upregulated the anti-apoptotic molecule Bcl-2 to a greater extend in
      HEK293 cells expressing L1. In the ovarian carcinoma cell line OVMz, the
      depletion of L1 by RNA interference sensitized cells for apoptosis induction. No
      changes in activation of ERK or FAK were observed after L1 knockdown. The
      selection of m130 ovarian carcinoma or SW707 colon carcinoma cells with cisplatin
      leads to upregulated expression of L1. CONCLUSIONS: Our results suggest a link
      between L1 expression and chemoresistance of ovarian carcinomas. Upregulation of
      L1 after cisplatin treatment might indicate a more malignant tumor phenotype
      given the established role of L1 in cell motility and invasion.

PMID- 17030350
TI  - Heparanase expression correlates with poor survival in metastatic ovarian
      carcinoma.
AB  - OBJECTIVE: To analyze the expression of Heparanase, an enzyme involved in cancer
      metastasis and angiogenesis, in ovarian and breast carcinoma cells in effusions.
      METHODS: Heparanase protein expression was analyzed in malignant effusions from
      ovarian (=200) and breast (=41) carcinoma patients using immunocytochemistry. The
      levels of secreted heparanase were analyzed in 45 effusion supernatants using a
      newly established ELISA test. Heparanase expression levels were analyzed for
      clinical significance. RESULTS: Heparanase was expressed at the cell membrane in
      106/200 (53%) ovarian and 22/41 (54%) breast carcinomas. Cytoplasmic expression
      was found in 180/200 (90%) ovarian and 26/41 (63%) breast carcinomas. Reactive
      mesothelial cells showed frequent cytoplasmic, but not membrane expression. ELISA
      showed secreted heparanase in all 45 analyzed effusions. Higher levels were
      detected in peritoneal compared to pleural effusions (p=0.031). In univariate
      survival analysis of ovarian carcinoma patients with post-chemotherapy effusions,
      membrane expression in >5% of tumor cells correlated with shorter overall
      survival (OS, p=0.013). FIGO stage (p=0.03 for all patients, p=0.045 for those
      with post-chemotherapy specimens) and response to first-line chemotherapy
      (p<0.0001 for all patients, p=0.049 for those with post-chemotherapy specimens)
      were the clinical parameters related to OS. In Cox analysis of this subset of
      patients, heparanase expression (p=0.02) and response to chemotherapy (p=0.049)
      were independent predictors of poor OS. Heparanase expression did not correlate
      with survival in breast carcinoma. CONCLUSIONS: Our data show that heparanase is
      frequently expressed in metastatic gynecologic adenocarcinomas, and that it is
      secreted into the effusion fluid in body cavities. The correlation between
      heparanase expression and poor survival in ovarian carcinoma suggests a role for
      this molecule in ovarian cancer metastasis and supports its role as a marker of
      aggressive clinical behavior at disease recurrence.

PMID- 17030351
TI  - COX-2 and survivin are overexpressed and positively correlated in endometrial
      carcinoma.
AB  - OBJECTIVES: To investigate the expressions of survivin and Cyclooxygenase-2 (COX
      2), and their possible correlations in the development of endometrial
      adenocarcinoma (EC). We also looked at their association with classical
      prognostic factors in EC. To our knowledge, this is the first time survivin
      expression is investigated in terms of its relation to COX-2 in the developmental
      pathway of EC. METHODS: Archived tissue samples of 50 EC, 30 endometrial
      hyperplasia and 20 proliferative endometrium were selected and
      immunohistochemically analyzed for survivin and COX-2 expression. RESULTS: Both
      survivin and COX-2 were overexpressed in hyperplasia and endometrial
      adenocarcinoma cases compared to proliferative endometrium, which was
      statistically significant (p=0.01, p=0.02, respectively). Among EC cases,
      survivin and COX-2 were strongly positive in 38 (76%) and 30 (60%) patients,
      respectively. Furthermore, we found survivin and COX-2 to be positively
      correlated, which was also statistically significant (p=0.0001, r=0.46). Neither
      survivin nor COX-2 expression was correlated with classical prognostic factors of
      endometrial carcinoma such as myometrial invasion, grade or lymph node metastasis
      (p>0.05). Neither COX-2 nor survivin had an impact on overall survival (p>0.05).
      CONCLUSIONS: Both survivin and COX-2 are overexpressed, and they seem to be early
      events in the occurrence of EC. Moreover, protein products of these two genes are
      positively correlated. COX-2 and survivin might share a common molecular pathway
      or enhance each other's actions in the developmental pathway of EC. Molecular
      basis of such a relationship should be further investigated in endometrial
      carcinogenesis.

PMID- 17030352
TI  - Expression of class III beta tubulin in cervical cancer patients administered
      preoperative radiochemotherapy: correlation with response to treatment and
      clinical outcome.
AB  - OBJECTIVES: Alterations of the beta subunit of tubulin have been reported to be
      predictive of resistance to radiation and antitubulin agents in several solid
      tumors. The aim of the study was to investigate the clinical role of beta III
      tubulin expression as prognostic factor for survival and as a predictive
      parameter of response to preoperative radiochemotherapy in a single institutional
      series of locally advanced cervical cancer (LACC) patients. METHODS: The study
      included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic
      University of Rome and Campobasso between January 1998 and January 2005.
      Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III
      tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained
      tumor cells was arbitrarily chosen as cut-off value to distinguish cases with
      high versus low beta III tubulin content. RESULTS: In the whole series, beta III
      tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage
      of positively stained cells ranged from 0 to 100% (median=10%). The percentages
      of cases with high beta III tubulin expression were shown not to be differently
      distributed according to clinico-pathological characteristics. There was no
      statistically significant difference in the distribution of cases with high beta
      III tubulin expression according to clinical and pathological response to
      treatment. During the follow-up period, recurrence and death of disease occurred
      in 15 and 13 cases, respectively. There was no difference in disease-free and
      overall survival in cases with high versus low beta III tubulin expression.
      CONCLUSIONS: The assessment of class III beta tubulin status seems of little
      usefulness in order to identify LACC patients with poor chance of response to
      concomitant radiochemotherapy and unfavorable prognosis.

PMID- 17030353
TI  - The impact of age in the outcome of patients with advanced or recurrent cervical
      cancer after platinum-based chemotherapy.
AB  - OBJECTIVES: Cervical cancer is a disease of middle-aged and elderly but still
      there are young women diagnosed with advanced disease that is incurable with
      local treatment and is treated with platinum-based combination chemotherapy. It
      is unknown whether these young patients have a poorer outcome compared to older
      patients or whether elderly patients have inferior outcome than younger patients
      when treated with combination chemotherapy. METHODS: We compared the outcome
      between young (<35), elderly (>70) and middle-aged (35-70) women who were treated
      with platinum-based combination chemotherapy for advanced, recurrent or
      persistent disease. RESULTS: Two hundred and eighteen patients were included in
      our database. The baseline clinical and disease characteristics were not
      different between age groups but anemia and thrombocytosis were more frequent in
      younger patients. Median survival for all patients was 13.4 (95%CI 11-15.8)
      months while survival of patients<35 years of age was 9 months (95% CI 5.8-12),
      of patients older than 70 was 10 months (95% CI 6.9-13) of patients 35 to 70
      years of age was 14.5 months (95% CI 11-18) (p=0.004). Multiple factors were
      significant for survival in univariate analysis but only weight loss, pain score
      and relapse inside an irradiated filed were significant predictors of outcome in
      multivariate analysis. CONCLUSIONS: Very young (<35) and elderly (>70) patients
      have a worse prognosis after treatment with combination chemotherapy for advanced
      or recurrent cervical cancer. Nevertheless, this difference is not significant
      when adjusted for other prognostic factors.

PMID- 17030354
TI  - Prognostic factors responsible for survival in sex cord stromal tumors of the
      ovary--an analysis of 376 women.
AB  - OBJECTIVE: To evaluate prognostic factors that impact on the survival of women
      with ovarian sex cord stromal tumors (SCST). METHODS: Data including age at
      diagnosis, stage, histology, grade, treatment, and survival were extracted from
      the 1988-2001 Surveillance, Epidemiology, and End Results Program. Kaplan-Meier
      and Cox proportional hazards analyses were used to determine the predictors for
      survival. RESULTS: 376 women (median age: 51) with ovarian sex cord stromal cell
      tumors were identified, including 339 with granulosa cell and 37 with Sertoli
      Leydig cell tumors. 265 (71%) patients had stage I, 39 (10%) stage II, 40 (11%)
      stage III, and 32 (8%) had stage IV disease. Women with stage I-II disease had a
      5-year disease-specific survival of 95% compared to 59% in those with stage III
      IV cancers (p<0.001). Patients<or=50 years had a survival advantage over those>50
      years (93% vs. 84%, p<0.001). This age-associated survival advantage was observed
      for early (97% vs. 92%, p=0.003), but not for advanced-staged (68% vs. 53%,
      p=0.09) patients. 110 patients with stage I-II disease underwent conservative
      surgery without hysterectomy. The survival for this group was similar to patients
      who underwent a standard surgery including a hysterectomy (94.8% and 94.9%,
      p=0.38). On multivariate analysis, age<or=50 (p=0.001) and early-stage disease
      (p<0.001) remained significant prognostic factor for improved survival.
      CONCLUSIONS: Younger age and early-stage disease are important predictors for
      improved survival in patients with ovarian sex cord stromal tumors. Conservative
      surgical treatment for early-staged patients wishing to retain fertility appears
      to be a safe alternative.

PMID- 17030355
TI  - A mathematical theory for temporal changes in tolerance to the behavioral effects
      of alcohol.
AB  - Temporal changes in the tolerance to alcohol are rarely discussed. In the
      behavioral theory proposed here, the rate of increase in tolerance during alcohol
      exposure is described by linear equations with zero intercept. These equations
      describe the rate of tolerance growth for acute tolerance, the rate of tolerance
      growth after alcohol dosing (chronic tolerance), and, for cases in which
      tolerance has been conditioned, the equations also describe changes in the rate
      of growth of tolerance when the stimulus set changes. This theory does not
      explain tolerance acquisition, but may be useful in investigating the
      physiological basis for tolerance acquisition because it provides numerical
      values for momentary tolerance that can be compared with concurrent physiological
      changes. The theory is testable and most of the published behavioral data on non
      conditioned tolerance are consistent with the proposed theory. New empirical data
      on conditioned tolerance are needed to evaluate the proposed theory, and the
      design for an evaluation is suggested here. Despite its limitations, the theory
      serves as one example of what a mathematical theory for tolerance might be and
      may stimulate the development of competing theories with which it could be
      compared empirically.

PMID- 17030356
TI  - Healthy lifestyles are associated with higher levels of perforin, granulysin and
      granzymes A/B-expressing cells in peripheral blood lymphocytes.
AB  - OBJECTIVE: It is well documented that natural killer (NK) cells provide host
      defense against tumors and viruses. We previously showed that lifestyle affects
      human NK and LAK activities. In order to explore the underlying mechanism, we
      investigated the effect of lifestyle on intracellular perforin, granulysin, and
      granzymes A/B in peripheral blood lymphocytes (PBL). METHODS: 114 healthy male
      subjects, aged 20-59 years, from a large company in Osaka, Japan were selected
      with informed consent. The subjects were divided into groups reporting good,
      moderate, and poor lifestyles according to their responses on a questionnaire
      regarding eight health practices (cigarette smoking, alcohol consumption,
      sleeping hours, working hours, physical exercise, eating breakfast, balanced
      nutrition, and mental stress). Peripheral blood was taken, and numbers of NK, T,
      perforin, granulysin, and granzymes A/B-expressing cells in PBL were measured by
      flow cytometry. RESULTS: Subjects with good or moderate lifestyle showed
      significantly higher numbers of NK, and perforin, granulysin, and granzymes A/B
      expressing cells and a significantly lower number of T cells in PBL than subjects
      with poor lifestyle. Among the eight health practices, cigarette smoking,
      physical exercise, eating breakfast, and balanced nutrition significantly affect
      the numbers of NK, T cells, perforin, granulysin, and/or granzymes A/B-expressing
      cells, and alcohol consumption significantly affects the number of granzyme A
      expressing cells. On the other hand, mental stress, sleeping, and working hours
      had no effect on those parameters. CONCLUSIONS: Taken together, these findings
      indicate that poor lifestyle significantly decreases the numbers of NK, perforin,
      granulysin, and granzymes A/B-expressing cells in PBL.

PMID- 17030357
TI  - Nasolabial cysts: clinical features, diagnosis, and treatment.
AB  - The aim of this study was to review our experience, examine the clinical and
      pathological features of nasolabial cysts, and to provide a basis for the
      diagnosis and treatment in an Asian population. We made a retrospective review of
      patients with nasolabial cysts who were treated at the Department of
      Otolaryngology, Tan Tock Seng Hospital between January 1999 and December 2004.
      Clinical data, presenting symptoms, clinical features, pathological findings,
      preoperative investigations, treatment, and outcome were analysed for each case.
      We found 17 patients with nasolabial cysts. The findings of adult onset, higher
      incidence among women and preponderance on the left side confirmed current
      opinion. The clinical diagnosis of nasolabial cyst was accurate in all cases.
      Preoperative computed tomograms (CTs) done for one patient did not alter the
      management. All patients had the cysts excised completely through a sublabial
      incision. Breaches of the nasal vestibular mucosa healed spontaneously without
      repair. Histopathological examination showed that cysts were lined with
      pseudostratified columnar (n=9), stratified squamous (n=4), mixed respiratory and
      squamous epithelium (n=3), and simple cuboidal epithelium (n=1). No patient
      developed complications or recurrences. Nasolabial cysts are relatively common in
      Singapore, and the diagnosis must be kept in mind if they are to be treated
      early. Diagnosis is based on clinical features and the treatment of choice is
      complete excision.

PMID- 17030358
TI  - Cherubism: long-term follow-up of 2 patients in whom it regressed without
      treatment.
AB  - Cherubism is a rare hereditary, self-limiting fibrous dysplasia characterised by
      painless enlargement of the jaws in childhood. Although, it is accepted that the
      lesions of cherubism are eventually replaced by bone, there have been few long
      term follow-up reports with clinicoradiographic documentation of spontaneous
      remission of the disease, without treatment. We report two cases of cherubic boys
      who were followed for 17 and 19 years. Clinicoradiographic examination during
      this period showed regression of the disease without surgical correction.

PMID- 17030359
TI  - Early pregnancy diagnosis by palpation per rectum: influence on embryo/fetal
      viability in dairy cattle.
AB  - The objective was to estimate the effect of palpation per rectum (for early
      pregnancy diagnosis) on embryo/fetal viability in dairy cattle. A controlled,
      randomized block-design experiment with two blocks, one by category, and the
      other by number of embryos, was conducted. Five-hundred-and-twenty pregnant dairy
      cows and heifers with a viable embryo detected by transrectal ultrasonography
      (TRUS) between days 29 and 32 after AI were included. The pregnant females were
      randomly allocated into two nearly equal groups: palpation per rectum (PAL group;
      n=258) and no palpation per rectum (NPAL group; n=262). The PAL group was
      submitted to palpation per rectum (PPR) using the fetal membrane slip (FMS)
      technique once between days 34 and 41 of pregnancy. The fetal membrane slip
      consisted of compressing the pregnant uterine horn and allowing the
      chorioallantoic membrane to slip between the fingers. Both groups were submitted
      to two additional TRUS at days 45 and 60 of pregnancy, to monitor the potential
      immediate and delayed deleterious effects of PPR on embryo and fetal viability,
      respectively. A diagnosis of embryo/fetal death was made when there was no
      embryo/fetal heart beat or the absence of positive signs of pregnancy in an
      animal previously diagnosed pregnant, or the presence of signs of embryo/fetal
      degeneration. The overall rate of embryo/fetal death was 14.0% (73/520).
      Embryonic death (10%; 52/520) was higher than fetal death (4.5%; 21/468;
      P<0.001). Embryo/fetal mortality was higher in cows (16.4%; 59/360) than in
      heifers (8.8%; 14/160; P<0.025) and in cattle with twin (25.5%; 12/47) versus
      singleton pregnancies (12.9%; 61/473; P<0.025), but was not different (P>0.05)
      between PAL (14.7%; 38/258) and NPAL (13.4%; 35/262). In conclusion, PPR between
      days 34 and 41 of pregnancy using the fetal membrane slip technique did not
      affect embryo/fetal viability.

PMID- 17030360
TI  - Influence of arginine-glycine-aspartic acid (RGD), integrins (alphaV and alpha5)
      and osteopontin on bovine sperm-egg binding, and fertilization in vitro.
AB  - Osteopontin (OPN), a phosphoprotein containing an arginine-glycine-aspartic acid
      (RGD) sequence, has been identified in cow oviduct epithelium and fluid. To
      investigate the potential role OPN in fertilization, we evaluated the ability of
      RGD peptide (arginine-glycine-aspartic), RGE peptide (arginine-glycine-glutamic
      acid), integrins alphaV and alpha5 antibodies and OPN antibody to influence
      bovine in vitro sperm-egg binding and fertilization. Treatment of sperm or
      oocytes with the RGD peptide prior fertilization significantly decreased in vitro
      sperm-egg binding and fertilization compared to the non-treated controls or those
      treated with RGE peptide. Binding and fertilization were also significantly
      decreased when in vitro matured bovine oocytes or sperm were pre-incubated with
      integrins alphaV and alpha5 antibodies at concentration ranging from 5 to 20
      microg/mL. Addition of a rabbit polyclonal IgG antibody against purified bovine
      milk OPN with sperm or/and oocytes decreased (P<0.05) fertilization compared to
      the in vitro-fertilized control. These data provided evidence that integrin
      ligands existed on bovine oocytes and spermatozoa that contained RGD recognition
      sequences, and that antibody to OPN, a protein that contains that RGD sequence,
      was capable of reducing sperm-egg binding and fertilization in vitro.

PMID- 17030362
TI  - Multi-spectroscopic study on interaction of bovine serum albumin with
      lomefloxacin-copper(II) complex.
AB  - The binding reactions of lomefloxacin-copper(II) complex (LMF-Cu) or LMF to
      bovine serum albumin (BSA) in physiological solution were investigated by multi
      spectroscopy. The binding constant, the number of binding sites and the binding
      distance between LMF-Cu or LMF and BSA were obtained by a fluorescence quenching
      method and according to the mechanism of Forster-type dipole-dipole non
      radioactive energy-transfer, respectively. Enthalpy and entropy changes for two
      systems were calculated to be -7.970 kJ mol(-1) and 47.438 J mol(-1)K(-1) for LMF
      BSA, -12.469 kJ mol(-1) and 33.542 J mol(-1)K(-1) for LMF-Cu-BSA, respectively.
      The highly positive values observed for the entropy give evidence for a strong
      interaction. The values of DeltaH and DeltaS in two systems are similar,
      indicating that electrostatic interactions in two systems play major role. The
      effect of LMF-Cu or LMF on the conformation of BSA was also analyzed by
      synchronous fluorescence, three-dimensional fluorescence and circular dichroism
      spectra. The results showed that the presence of Cu ion in LMF-Cu can affect the
      conformation of BSA to some degree. All the results revealed that the addition of
      copper ion promotes the interaction of lomefloxacin with bovine serum albumin.

PMID- 17030361
TI  - Butyrolactone I reversibly alters nuclear configuration, periooplasmic
      microtubules and development of porcine oocytes.
AB  - In the present study, we investigated the effects of specific cdc2 kinase
      inhibitor, butyrolactone I (BL I) on the prevention of germinal vesicle
      breakdown, changes of microtubular structures, and development of porcine oocytes
      after removal of the drug. In Experiment 1, cumulus-oocyte complexes (COCs) were
      cultured (44 h) in NCSU-23 medium containing different concentrations of BL I.
      The percentages of oocytes remaining at GV stage were 0, 0, 32, 80, and 84%
      (P<0.05), and the maturation rates were 86, 63, 30, 0, and 0% (P<0.05) for
      oocytes treated with 0, 10, 20, 40, and 80 microM of BL I, respectively. When
      oocytes were released from BL I incubation (Experiment 2) and cultured for an
      additional 44 h, 79, 84, and 83% of oocytes resumed meiosis, but only 52, 38 and
      17% of oocytes reached normal metaphase II (MII) stage in the groups treated with
      20, 40 and 80 microM BL I, respectively. In Experiments 3-5, reversibility and
      development of oocytes and embryos were evaluated after removal of the inhibitor.
      A reduced duration of BL I incubation (22 h) at 20 microM increased the
      percentage of oocytes remaining at the GV stage compared to the control group
      (85% versus 9%, P<0.05). Blastocyst rates were lower in treatment groups than in
      the control (44 h) group (0-14% versus 24%; P<0.05). However, all developing
      blastocysts possessed similar cell numbers, regardless of the drug-treated or non
      treated controls. Taken together, treatment with 20-80 microM of BL I effectively
      prevented the resumption of meiosis and polymerization of periooplasmic
      microtubules. Furthermore, reversibility of the oocytes after reduced duration of
      BL I treatment was satisfactory.

PMID- 17030363
TI  - Glycosaminoglycan-targeted fixation for improved bioprosthetic heart valve
      stabilization.
AB  - Numerous crosslinking chemistries and methodologies have been investigated as
      alternative fixatives to glutaraldehyde (GLUT) for the stabilization of
      bioprosthetic heart valves (BHVs). Particular attention has been paid to valve
      leaflet collagen and elastin stability following fixation. However, the stability
      of glycosaminoglycans (GAGs), the primary component of the spongiosa layer of the
      BHV, has been largely overlooked despite recent evidence provided by our group
      illustrating their structural and functional importance. In the present study we
      investigate the ability of two different crosslinking chemistries: sodium
      metaperiodate (NaIO(4)) followed by GLUT (PG) and 1-Ethyl-3-(3
      dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) followed by GLUT
      (ENG) to stabilize GAGs within BHV leaflets and compare resulting leaflet
      characteristics with that of GLUT-treated tissue. Incubation of fixed leaflets in
      GAG-degrading enzymes illustrated in vitro resistance of GAGs towards degradation
      in PG and ENG treated tissue while GLUT fixation alone was not effective in
      preventing GAG loss from BHV leaflets. Following subdermal implantation,
      significant amounts of GAGs were retained in leaflets in the ENG group in
      comparison to GLUT-treated tissue, although GAG loss was evident in all groups.
      Utilizing GAG-targeted fixation did not alter calcification potential of the
      leaflets while collagen stability was maintained at levels similar to that
      observed in conventional GLUT-treated tissue.

PMID- 17030364
TI  - On the presence of enriched amounts of 235U in hot particles from the terrestrial
      area affected by the Palomares accident (Spain).
AB  - The characterisation by ICP-MS of an isolated Pu-U hot particle originating from
      the nuclear weapons accident in Palomares (Spain) shows, for the first time, that
      its uranium content is highly enriched in (235)U. The enrichment has been
      confirmed by independent analyses of two surface soil samples collected in a
      heavily contaminated area close to the impact point of one of the bombs. This
      finding clarifies better the composition of the weapons involved in the accident
      and is of importance when the inventory of U and Pu in the contaminated area are
      to be calculated.

PMID- 17030365
TI  - Magnetic approach to normalizing heavy metal concentrations for particle size
      effects in intertidal sediments in the Yangtze Estuary, China.
AB  - In this study, mineral magnetic, particle size and geochemical analyses were
      conducted on intertidal sediments from the Yangtze Estuary to examine the
      feasibility of heavy metal concentrations normalization using magnetic
      techniques. Susceptibility of Anhysteretic Remanent Magnetization (chiARM), the
      ratio of chiARM to SIRM (Saturation Isothermal Remanent Magnetization) and
      susceptibility (chiARM/SIRM and chiARM/chi, respectively), and to a lesser
      degree, frequency dependent susceptibility (chifd), displayed significant
      correlations with the fine sediment fraction (<16 microm). The strong
      relationships between chiARM and heavy metals can be explained by the role of
      particle size and iron oxides in controlling metal concentrations. This study
      demonstrates that chiARM can be used to normalize for particle size effects as
      efficiently as common reference elements such as Al. Furthermore, the rapid and
      non-destructive nature of mineral magnetic measurement technique means that
      chiARM has a considerable application value in environmental quality monitoring
      and related studies.

PMID- 17030366
TI  - Calcium microdomains: organization and function.
AB  - Microdomains of Ca(2+), which are formed at sites where Ca(2+) enters the
      cytoplasm either at the cell surface or at the internal stores, are a key element
      of Ca(2+) signalling. The term microdomain includes the elementary events that
      are the basic building blocks of Ca(2+) signals. As Ca(2+) enters the cytoplasm,
      it produces a local plume of Ca(2+) that has been given different names (sparks,
      puffs, sparklets and syntillas). These elementary events can combine to produce
      larger microdomains. The significance of these localized domains of Ca(2+) is
      that they can regulate specific cellular processes in different regions of the
      cell. Such microdomains are particularly evident in neurons where both pre- and
      postsynaptic events are controlled by highly localized pulses of Ca(2+). The
      ability of single neurons to process enormous amounts of information depends upon
      such miniaturization of the Ca(2+) signalling system. Control of cardiac cell
      contraction and gene transcription provides another example of how the parallel
      processing of Ca(2+) signalling can occur through microdomains of intracellular
      Ca(2+).

PMID- 17030367
TI  - Ca2+ microdomains and the control of insulin secretion.
AB  - Nutrient-induced increases in intracellular free Ca(2+) concentrations are the
      key trigger for insulin release from pancreatic islet beta-cells. These Ca(2+)
      changes are tightly regulated temporally, occurring as Ca(2+) influx-dependent
      baseline oscillations. We explore here the concept that locally high [Ca(2+)]
      concentrations (i.e. Ca(2+) microdomains) may control exocytosis via the
      recruitment of key effector proteins to sites of exocytosis. Importantly, recent
      advances in the development of organelle- and membrane-targeted green fluorescent
      protein (GFP-) or aequorin-based Ca(2+) indicators, as well as in rapid imaging
      techniques, are providing new insights into the potential role of these Ca(2+)
      microdomains in beta-cells. We summarise here some of the evidence indicating
      that Ca(2+) microdomains beneath the plasma membrane and at the surface of large
      dense core vesicles may be important in the normal regulation of insulin
      secretion, and may conceivably contribute to "ATP-sensitive K(+)-channel
      independent" effects of glucose. We also discuss evidence that, in contrast to
      certain non-excitable cells, direct transfer of Ca(2+) from the ER to
      mitochondria via localised physical contacts between these organelles is
      relatively less important for efficient mitochondrial Ca(2+) uptake in beta
      cells. Finally, we discuss evidence from single cell imaging that increases in
      cytosolic Ca(2+) are not required for the upstroke of oscillations in
      mitochondrial redox state, but may underlie the reoxidation process.

PMID- 17030368
TI  - Carcinogenicity classification of vanadium pentoxide and inorganic vanadium
      compounds, the NTP study of carcinogenicity of inhaled vanadium pentoxide, and
      vanadium chemistry.
AB  - It is argued that, because of inherent weaknesses in design and procedure, the
      U.S. National Toxicology Program study of the carcinogenicity of inhaled vanadium
      pentoxide does not provide adequate evidence to support the classification by
      regulatory authorities of vanadium pentoxide as a Group 2B (possible) human
      carcinogen. The extension by one regulatory authority of the carcinogenicity
      classification for vanadium pentoxide to cover all vanadium compounds is also
      questioned. Such an extension implies that the toxic effect of some unknown
      vanadium species is more powerful than that of any oxygen species generated from
      the oxygen atoms in vanadium pentoxide, and that vanadium in any form can be
      converted in vivo to an undefined toxic species. There is no experimental or
      theoretical basis supporting this hypothesis. For oxygen-containing compounds
      like vanadium pentoxide, there is a need for some form of toxicity classification
      related to their oxygen content since it is likely to be the most reactive
      component of such compounds. For all particulates, such as those of crystalline
      vanadium pentoxide, the special toxicity of particulates, and especially
      nanoparticles, also needs separate consideration and classification.

PMID- 17030369
TI  - Biomonitoring equivalents: a screening approach for interpreting biomonitoring
      results from a public health risk perspective.
AB  - Advances in both sensitivity and specificity of analytical chemistry have made it
      possible to quantify substances in human biological specimens, such as blood,
      urine, and breast milk, in specimen volumes that are practical for collection
      from individuals. Research laboratories led by the Centers for Disease Control
      and Prevention (CDC) in its series National Report on Human Exposure to
      Environmental Chemicals [Centers for Disease Control and Prevention (CDC), 2005.
      Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No.
      05-0570.] are dedicating substantial resources to designing and conducting human
      biomonitoring studies and compiling biomonitoring data for the general
      population. However, the ability to quantitatively interpret the results of human
      biomonitoring in the context of a health risk assessment currently lags behind
      the analytical chemist's ability to make such measurements. The traditional
      paradigm for human health risk assessment of environmental chemicals involves
      comparing estimated daily doses to health-based criteria for acceptable, safe, or
      tolerable daily intakes (for example, reference doses [RfDs], tolerable daily
      intakes [TDIs], or minimal risk levels [MRLs]) to assess whether estimated doses
      exceed such health screening levels. However, biomonitoring efforts result in
      measured chemical concentrations in biological specimens (the result of
      absorption, distribution, metabolism and excretion of administered doses) rather
      than estimated intake doses. Quantitative benchmarks of acceptable or safe
      concentrations in biological specimens (analogous to RfDs, TDIs, or MRLs) needed
      to interpret these levels exist for very few chemicals of environmental interest.
      This paper discusses issues inherent in converting existing health screening
      benchmarks based on intake doses to screening levels for evaluating biomonitoring
      data, and presents methods and approaches that can be used to derive such
      screening levels (termed "Biomonitoring Equivalents," or BEs) for a range of
      chemicals and biological media.

PMID- 17030370
TI  - The use of myocardial and testicular end points as a basis for estimating a
      proposed tolerable daily intake for sodium monofluoroacetate (1080).
AB  - This paper presents the development of a tolerable daily intake (TDI) for sodium
      monofluoroacetate (1080) using the quantal myocardial and testicular toxicity end
      points derived from the traditional NOAEL and newer benchmark dose (BMD) methods.
      1080 is a highly toxic vertebrate pesticide that has been proven to be effective
      in controlling possums and other pests. By convention, the TDIs are derived using
      the traditional no-observed-adverse-effect-level (NOAEL) and applying appropriate
      default uncertainty factors (UF). In addition to the default UF, a statistically
      derived UF was also employed in deriving the TDI. The TDIs derived from the NOAEL
      and BMD approach, 0.075 and 0.10 mg/kg bw/day, respectively, were compared. The
      resulting TDI estimates using the BMDL, a statistical lower confidence bound on
      the BMD, were generally consistently slightly higher than those derived using the
      NOAEL approach. Based on the best fit of modelled dose-response data, a TDI of
      0.03 micro g/kg bw/day is proposed for human health risk assessment of 1080.

PMID- 17030372
TI  - An examination of income-related disparities in the nutritional quality of food
      selections among Canadian households from 1986-2001.
AB  - Socio-economic disparities in nutrition have been documented in numerous
      countries, and have been linked to health inequalities. Social and economic
      policy changes occurring over the last several years have resulted in growing
      levels of income inequality in many countries. However, the extent to which these
      temporal changes have affected nutrition disparities is largely unknown. Our
      research examined income-related disparities in the nutritional quality of food
      selections among Canadian households from 1986 to 2001. Data from the 1986, 1992,
      1996 and 2001 Family Food Expenditure surveys were pooled together (n=35048). The
      relationships between household income and the nutritional quality of food
      purchases (considering nutrients both as absolute amounts and adjusted for
      energy, and total energy density) were estimated using general linear models,
      including tests of significance for differences across the survey years. Results
      revealed significant positive relationships between income and most nutrients,
      which persisted over time, and for some nutrients grew stronger. One exception
      was folate, where the positive relationship between income and folate
      (independent of energy) was no longer apparent in 2001; this could be attributed
      to the mandatory fortification of some cereal grain products with folic acid,
      which came into effect in 1998, resulting in greater availability of folate from
      grain products. There was also a significant negative relationship between income
      and total energy density (ratio of food energy to food weight), which persisted
      across the survey years. At a time of growing income inequality and worsening
      problems of poverty, food policy makers need to pay attention to the potential
      for policy interventions to exacerbate or improve nutrition disparities.

PMID- 17030373
TI  - Marital status, intergenerational co-residence and cardiovascular and all-cause
      mortality among middle-aged and older men and women during wartime in Beirut:
      gains and liabilities.
AB  - Studies from the West have shown an increased risk of mortality with various
      indicators of social isolation. In this study, we examine associations of marital
      status and intergenerational co-residence with mortality in Lebanon, a country
      that suffered wars and atrocities for almost 16 years. Using data from a
      retrospective 10-year follow-up study (1984-1994) among 1567 adults aged 50 years
      and older in Beirut, cardiovascular disease and all-cause mortality rates (per
      1000 person-years) were computed for men and women separately. Age-adjusted
      Mantel-Haenszel rate ratios (RR) and their 95% confidence intervals (CI) were
      estimated, and associations were examined using multivariate Poisson regression
      analysis. Most men (91.3%) were married at baseline, in contrast to only 55.4% of
      women. Compared to men, women were more likely to be living in one- and three
      generation households and with a married child at baseline. While widowhood was
      associated with an increased risk of all-cause mortality among men only, being
      never married was associated with a higher CVD mortality risk among men and
      women. The presence of an adult married child was associated with a significantly
      higher mortality risk for men and women, even after adjusting for household
      socioeconomic indicators, marital status, lifestyle variables or pre-existing
      health-related conditions (hypertension, cholesterol, and diabetes) at baseline.
      The popular belief that co-residence with adult children reflects greater support
      networks and an avenue for old age security may not be a valid presumption in the
      Lebanese context during times of war.

PMID- 17030371
TI  - Mechanisms of vasoactive intestinal peptide-elicited coronary vasodilation in the
      isolated perfused rat heart.
AB  - The present study investigated the potential role of vasoactive intestinal
      peptide (VIP) receptors, VPAC1 and VPAC2, in VIP-elicited coronary vasodilation
      of the isolated perfused rat heart. Additional studies determined the role of ATP
      sensitive (K(ATP)) and voltage-gated K(+) (K(V)) channels in the VIP-elicited
      coronary vasodilation. Both the selective VPAC1 agonist, K15,R16,L27VIPl-7GRF8
      27, and the selective VPAC2 agonist, RO25-1553, decreased coronary vascular
      resistance (CVR) in a dose-dependent manner, with EC(50) values of 1.67x10(-9)M
      and 7.11x10(-9)M, respectively (VPAC1 vs VPAC2 agonist, P<0.05). K15,R16,L27VIP1
      7GRF8-27 and RO25-1553 maximally reduced CVR by -42+/-4% and -39+/-6% at 1x10(-8)
      and 3x10(-8)M, respectively. VIP at 1x10(-10)M decreased CVR by -14+/-2% in the
      absence (vehicle), by -11+/-3% in the presence of the nonselective VIP receptor
      antagonist VIP10-28 (1x10(-7)M; P>0.05 vs. vehicle) and by only -4+/-2% in the
      presence of the selective VPAC2 receptor antagonist PACAP6-38 (1x10(-7)M; P<0.05
      vs. vehicle). In additional studies, VIP at 1x10(-10)M decreased CVR by -22+/-1%
      in the absence (control) and by only -10+/-2% in the presence of the nonselective
      K(+) channel blocker tetrabutylammonium (3x10(-4)M; P<0.05 vs. control). VIP
      reduced CVR by -4+/-1% in the presence of the K(ATP) channel blocker
      glibenclamide (3x10(-6)M; P<0.05 vs control) and by -28+/-2% in the presence of
      the K(V) channel blocker 4-aminopyridine (3x10(-4)M; P>0.05 vs control). Thus,
      selective VPAC1 and VPAC2 receptor activation in the coronary circulation
      produces vasodilation and the VIP-elicited coronary vasodilation involves
      activation of VPAC2 receptors and K(ATP) but not K(V) channels. In addition,
      VIP10-28 does not effectively block coronary vascular VIP receptors.

PMID- 17030374
TI  - The suppressor of cytokine signalling-1 (SOCS-1) gene is overexpressed in
      Philadelphia chromosome negative chronic myeloproliferative disorders.
AB  - The suppressor of cytokine signalling-1 (SOCS-1) is a negative regulator of
      signal transduction mediated by cytoplasmic tyrosine kinases such as the Janus
      kinases (JAKs). We investigated SOCS-1 expression in bone marrow cells from
      Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-)
      CMPD) and normal haematopoiesis (n=121), and additionally in peripheral blood
      samples (n=18). Except for chronic idiopathic myelofibrosis harbouring wild-type
      JAK2, other Ph(-) CMPD expressed significantly higher SOCS-1 levels of up to 14
      fold compared to the control group (p<0.001) independent of the JAK2 status. The
      mononuclear cell fraction but not granulocytes in patients with Polycythaemia
      vera also significantly overexpressed SOCS-1. We conclude that up-regulation of
      the SOCS-1 gene might reflect a compensatory feedback mechanism with different
      emphasis among Ph(-) CMPD subtypes independent of an underlying JAK2 (V617F)
      mutation.

PMID- 17030375
TI  - Possible antipsychotic effects of minocycline in patients with schizophrenia.
AB  - We present two cases of patients with schizophrenia treated with minocycline.
      Minocycline (a second-generation tetracycline) is an established and safe broad
      spectrum antibiotic that crosses the blood-brain barrier, with additional
      efficacy for diseases such as acne and rheumatoid arthritis. Animal studies have
      suggested that minocycline may prevent progression of some neurological
      disorders. Moreover, it has been reported that minocycline might have
      antidepressant effects. We report two cases of acute schizophrenia with
      predominant catatonic symptoms that responded to minocycline.

PMID- 17030376
TI  - Decreased serum levels of transforming growth factor-beta1 in patients with
      autism.
AB  - BACKGROUND: The neurobiological basis for autism remains poorly understood. Given
      the key role of transforming growth factor-beta1 (TGF-beta1) in brain
      development, we hypothesized that TGF-beta1 plays a role in the pathophysiology
      of autism. In this study, we studied whether serum levels of TGF-beta1 are
      altered in patients with autism. METHODS: We measured serum levels of TGF-beta1
      in 19 male adult patients with autism and 21 age-matched male healthy subjects
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum levels
      (7.34+/-5.21 ng/mL (mean+/-S.D.)) of TGF-beta1 in the patients with autism were
      significantly (z=-5.106, p<0.001) lower than those (14.48+/-1.64 ng/mL (mean+/
      S.D.)) of normal controls. However, there were no marked or significant
      correlations between serum TGF-beta1 levels and other clinical variables,
      including Autism Diagnostic Interview-Revised (ADI-R) scores, Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS), aggression, Theory of Mind, and Intellectual
      Quotient (IQ) in patients. CONCLUSIONS: These findings suggest that decreased
      levels of TGF-beta1 may be implicated in the pathophysiology of autism.

PMID- 17030377
TI  - Characterization of the mobilization determinants of pAN12, a small replicon from
      Rhodococcus erythropolis AN12.
AB  - Bacteria belonging to the Gram-positive actinomycete species, Rhodococcus
      erythropolis, are diverse not only in terms of metabolic potentials but the
      plasmids they encode. It was shown previously that the R. erythropolis AN12
      genome harbors a 6.3kb cryptic plasmid called pAN12, which is a member of the
      pIJ101 family of plasmids. Here we show that pAN12 is conjugatively mobilizable
      into other rhodococcal strains. A series of plasmid deletion constructs were
      tested for loss of mobility to identify the pAN12 cis-acting conjugation
      requirement. In this way, an approximately 700bp region was found to be required
      for plasmid transmission. A small 61bp element within this region confers
      mobility to an otherwise non-mobilizable plasmid. Unlike pIJ101, which encodes
      all necessary factors for transfer, pAN12 mobility is dependent on the presence
      of an AN12 megaplasmid, pREA400.

PMID- 17030380
TI  - Hydroquinone: acute and subchronic toxicity studies with emphasis on
      neurobehavioral and nephrotoxic effects.
AB  - Hydroquinone (HQ) is a common water-soluble constituent of foods, an ingredient
      in skin lightening preparations, a photographic developer, and an antioxidant
      used in the preparation of industrial polymers. In this series of studies,
      aqueous solutions of HQ were given by gavage to male and female Sprague-Dawley
      rats to determine the acutely lethal dose, the clinical signs of behavioral
      toxicity associated with doses at or near a dose causing mortality, and the
      effects of the administration of dose levels resulting in acutely observable
      behavioral effects when administered 5 days/week for 13 weeks. The acute dermal
      toxicity of HQ in rabbits was also determined. For the acute oral toxicity study,
      groups of five male and five female rats were administered single oral doses of
      375, 345, 315, or 285 mg/kg. At all dose levels, animals exhibited minor to
      moderate tremors and minor convulsions within the first hour after dosing. The
      acute oral LD50 value for both sexes combined was >375 mg/kg. Dermal application
      of 2000 mg/kg HQ to rabbits under an occlusive wrap for 24 h did not result in
      neurobehavioral effects or mortality. Subchronic exposure was accomplished by
      administration of doses of 200, 64, 20, or 0 mg/kg/day of HQ in water to groups
      of male and female rats study (10/sex/group). A functional observational battery
      (FOB) was used to detect neurobehavioral effects prior to HQ exposure and
      postexposure at 1, 6, and 24 h and 7, 14, 30, 60, and 91 days. Daily clinical
      observations were also recorded for each animal. Doses of 200 or 64 mg/kg HQ
      resulted in acutely observable behavioral effects including tremors and reduced
      activity. Tremors occurred within one hour of dosing and resolved by the 6-h
      examination. Brain weights were not altered by HQ administration, but mean
      terminal body weight was reduced approximately 7% for the 200 mg/kg males.
      Neuropathologic examination of the CNS and PNS, including special stains for
      myelin and axonal process, did not reveal any morphologic lesions associated with
      HQ administration or secondary to repetitive CNS stimulation by HQ. The
      nephrotoxic effects observed in Fischer 344 rats after HQ exposure was not
      observed in this study with Sprague-Dawley rats. Oral doses of >or=64/mg/kg HQ
      resulted in acute neurobehavioral effects indicative of CNS stimulation; however,
      subchronic exposure to dose levels that produced repetitive CNS stimulation by HQ
      did not result in an exacerbation of acute stimulatory effects over time or
      morphologic changes in the CNS or PNS or nephrotoxicity.

PMID- 17030379
TI  - Transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid is
      enhanced by both ethanol consumption and sunscreen application.
AB  - Xenobiotics absorption is a health concern and skin is a major exposure site for
      many of these chemicals. Both alcohol consumption and topical sunscreen
      application act as transdermal penetration enhancers for model xenobiotics. The
      effect of combining these two treatments on transdermal absorption of the
      herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was therefore examined. Skin
      from rats ingesting low (1.5 g/kg) medium (4.3 g/kg) or high (6 g/kg) ethanol
      doses or saline control was treated with a commercially available sunscreen
      containing titanium dioxide and octyl methoxycinnimate and transdermal absorption
      of 2,4-D was monitored. Ethanol increased penetration by a factor of 1.9, 2.0 and
      2.5 for animals treated with 1.5, 4.3 and 6 g/kg respectively, demonstrating an
      ethanol-induced dose response. Sunscreen application to skin from ethanol gavaged
      rats caused 2,4-D absorption above that induced by ethanol alone by an additional
      factor of 1.3, 2.1 and 2.9 for 1.5, 4.3 and 6 g/kg respectively. Comparing 2,4-D
      transdermal absorption after exposure to both ethanol and sunscreen with a
      theoretical value (sum of penetration after ethanol or sunscreen treatment)
      demonstrates that these two treatments enhance additively at the higher doses
      tested. Results of this study emphasize the importance of limiting excessive
      alcohol consumption in individuals with potential herbicide exposure rather than
      discouraging the use of sunscreens, since the consequences of UV-induced skin
      cancer are far more series than the risks that would be associated with observed
      increases in chemical exposure.

PMID- 17030378
TI  - Supernatant of bacterial fermented soybean induces apoptosis of human
      hepatocellular carcinoma Hep 3B cells via activation of caspase 8 and
      mitochondria.
AB  - SC-1, the aqueous phase of soybean fermentation products by bacteria (Bacillus
      subtilis and Bacillus brevis), significantly inhibited the growth and
      clonogenesity of human hepatocellular (Hep 3B), mouse hepatocellular (ML-1), and
      human colorectal (HCT 116 and HT-29) carcinoma cells. Cytotoxicity of SC-1 in Hep
      3B cells was through the process of apoptosis characterizing by increase in cell
      population of sub-G(1) phase, fragmentation of DNA, and change of nuclear
      morphology. Treatment of Hep 3B cells with SC-1 activated caspase 8 and caspase
      3. Elevation of nuclear DNA fragmentation factor 40 (DFF40) and cleavage form of
      poly(ADP-ribose) polymerase (PARP) were also observed. SC-1 also activated
      intrinsic pathway via increase of pro-apoptotic (tBid, Bak and Bax) and decrease
      of anti-apoptotic (Bcl-2 and Bcl-x(L)) proteins on mitochondria, disruption of
      mitochondrial membrane potential, release of cytochrome c and Smac (second
      mitochondria-derived activator of caspase/direct IAP binding protein with low PI)
      from mitochondria, and activation of caspase 9. Inhibition on protein expression
      of Ku70 in cytosol and cyclooxygenase (COX)-2, but not COX-1, in whole cell
      lystes were revealed in SC-1-treated Hep 3B cells. These results suggest caspase
      8, Ku70 and mitochondria are involved in the antitumor mechanism of SC-1 in Hep
      3B cells.

PMID- 17030381
TI  - Protective effect of Ugni molinae Turcz against oxidative damage of human
      erythrocytes.
AB  - Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south
      of Chile. Infusions of its leaves have long been used in traditional native
      herbal medicine. The chemical composition of the leaves indicates the presence of
      polyphenols, which have antioxidant properties. In the present work, the
      antioxidant properties of U. molinae were evaluated in human erythrocytes exposed
      in vitro to oxidative stress induced by HClO. The experiments were carried out by
      scanning electron microscopy (SEM) and hemolysis measurements. The SEM
      observations showed that HClO induced a morphological alteration in the red blood
      cells from a discoid to an echinocytic form. According to the bilayer couple
      hypothesis, the formation of echinocytes indicates that HClO was inserted in the
      outer leaflet of the erythrocyte membrane. However, a concentration as low as 10
      microM gallic acid equivalents (GAE) U. molinae aqueous extract neutralized the
      shape change effect of HClO applied in a concentration as high as 0.25 mM. The
      significant protection of U. molinae aqueous extract was also shown in the
      hemolysis experiments. In fact, very low concentrations of the extract
      considerably reduced the deleterious capacity of HClO to induce hemolysis in red
      blood cells. It is concluded that the location of the extract components into the
      membrane bilayer and the resulting restriction on its fluidity might hinder the
      diffusion of HClO and its consequent damaging effects. This conclusion can also
      imply that this restriction could apply to the diffusion of free radicals into
      cell membranes and the subsequent decrease of the kinetics of free radical
      reactions.

PMID- 17030382
TI  - Acute and subchronic oral toxicity studies in rats of a hydrolyzed chicken
      sternal cartilage preparation.
AB  - Two acute and subchronic oral toxicity studies were conducted in rats to evaluate
      safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell
      Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic
      acid. In the acute oral toxicity study, five males and five females of Sprague
      Dawley rats were administered a single dose of 5000 mg of the test product per kg
      body weight and observed for 14 days. All animals survived and exhibited normal
      body weight gain throughout the study. Macroscopic necropsy examination conducted
      on day 15 revealed no gross pathological lesions in any of the animals. In the
      subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into
      four same-sex groups (10 animals/group). Animals in each group were administered
      daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for
      over 90 days. All animals survived and showed no significant changes in their
      body weights and histopathology. Although some differences were observed between
      the treated and control animals in several parameters, they were generally not
      dose-related or considered to be of toxicological significance. In conclusion,
      the results from the two oral toxicity studies with male and female young adult
      rats indicated that the test preparation from hydrolyzed chicken sternal
      cartilage collagen (BioCell Collagen II) was well tolerated at all four doses
      tested.

PMID- 17030383
TI  - Occupational exposure of hairdressers to [14C]-para-phenylenediamine-containing
      oxidative hair dyes: a mass balance study.
AB  - We monitored the exposure of hairdressers to oxidative hair dyes for 6 working
      days under controlled conditions. Eighteen professional hairdressers (3/day)
      coloured hairdresser's training heads bearing natural human hair (hair length:
      approximately 30 cm) for 6 h/working day with a dark-shade oxidative hair dye
      containing 2% [14C]-para-phenylenediamine (PPD). Three separate phases of hair
      dyeing were monitored: (A) dye preparation/hair dyeing, (B)
      rinsing/shampooing/conditioning and (C) cutting/drying/styling. Ambient air and
      personal monitoring samples (vapours and particles), nasal and hand rinses were
      collected during all study phases. Urine (pre-exposure, quantitative samples for
      the 0-12, 12-24, 24-48 h periods after start of exposure) and blood samples
      (blank, 4, 8 or 24 h) were collected from all exposed subjects. Radioactivity was
      determined in all biological samples and study materials, tools and washing
      liquids, and a [14C]-mass balance was performed daily. No adverse events were
      noted during the study. Waste, equipment, gloves and coveralls contained 0.41+/
      0.16%, dye mixing bowls 2.88+/-0.54%, hair wash 45.47+/-2.95%, hair+scalp 53.46+/
      4.06% of the applied radioactivity, respectively. Plasma levels were below the
      limit of quantification (10 ng PPDeq/mL). Total urinary 0-48 h excretion of [14C]
      levels ranged from a total of <2-18 microg PPDeq and was similar in subjects
      exposed during the different phases of hair dyeing. Minimal air levels at or
      slightly above the limit of quantification were found in a few personal air
      monitoring samples during the phases of hair dyeing and hair cutting, but not
      during the rinsing phase. Air area monitoring samples or nasal rinses contained
      no measurable radioactivity. Hand residues ranged from 0.006 to 0.15 microg
      PPDeq/cm2, and were found predominantly after the cutting/drying phase. The mean
      mass balance of [14C] across the six study days was 102.50+/-2.20%. Overall, the
      mean, total systemic exposure of hairdressers to oxidative hair dyes during a
      working day including 6 hair dyeing processes was estimated to be <0.36 microg
      PPDeq/kg body weight/working day. Our results suggest that (a) current safety
      precautions for the handling of hair dyes offer sufficient protection against
      local and systemic exposure and (b) professional exposure to oxidative hair dyes
      does not pose a risk to human health.

PMID- 17030384
TI  - Influence of colostrum treated by heat on immunity function in goat kids.
AB  - The aim was to evaluate the influence of goat colostrum treated by heat on immune
      function in kids. Thirteen newborn kids were fed untreated colostrum (group A)
      and 13 kids were fed colostrum treated by heat (56 degrees C, 30 min) (group B).
      Blood samples were obtained at eight time points between the ages of 0 h to 28
      days. Serum protein fractions, IgG levels and phagocytic activity of neutrophils
      were determined. A delayed type hypersensitivity (DTH) test was used, clinical
      status and body weight was recorded. There were no clinical signs of disease and
      no differences (P>0.05) on body weight between groups were noted. Kids from group
      B had less total protein levels and gamma-globulins than kids from group A
      (P<0.05). A decrease in serum IgG levels (P<0.05) was observed in kids from group
      B during all experiment. DTH response in kids from group B was lower (P<0.01)
      than group A, suggesting alteration on cellular immune system. No effects on
      phagocytic activity of the neutrophils were observed when both groups were
      compared (P>0.05). These results showed that colostrum treated by heat impaired
      some immunological parameters in kids, but these changes did not affect on
      clinical status or performance.

PMID- 17030385
TI  - Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis
      patients.
AB  - Lactoferrin (Lf) is a member of the transferrin family of iron-binding anti
      bacterial proteins, present in most exocrine secretions, such as saliva, and
      plays an important role in mucosal defense. In this study, we identified small Lf
      peptides with Con A low-affinity in the parotid saliva of chronic periodontitis
      patients by Con A two-dimensional immunoelectrophoresis, Con A affinity
      chromatography and Western blotting using anti-human Lf polyclonal Ab. N-terminal
      amino acid sequencing of the four Con A low-affinity Lf peptides confirmed them
      to be fragments of intact Lf. The detection ratio of the proteinase 3 (PR3)-like
      activity was elevated in the parotid saliva of periodontitis patients and was
      associated with the severity of clinical symptoms. PR3 protein was also detected
      in the parotid saliva of periodontitis patients, and PR3, but not human leukocyte
      elastase and cathepsin G, degraded intact Lf. Con A low-affinity saliva Lf
      peptides showed no anti-bacterial activity against Escherichia coli, and had a
      reduced iron-chelating capacity. Con A low-affinity saliva Lf peptides, PR3
      treated Lf preparation and two of four synthetic polypeptides induced the
      production of interleukin IL-6, monocyte chemoattractant protein-1 and IL-8, and
      the activation of NF-kappaB in human oral epithelial HSC-2 cells. Furthermore,
      concentrations of the Lf peptides in the parotid saliva of periodontitis patients
      were increased with a correlation to the severity of clinical symptoms. These
      results suggest that Lf in the parotid saliva of periodontitis patients was
      degraded into small peptides by the PR3-like activity with the capability to
      induce inflammatory mediators.

PMID- 17030386
TI  - [Diagnosis and management of cervicofacial congenital teratomas: about 4 cases,
      literature review and restatement].
AB  - Cervicofacial teratomas are rare developmental lesions, more often benign in
      their histology. They can lead to respiratory distress and death caused by airway
      obstruction at birth. Prenatal diagnosis raises on ultrasound examination
      precising locoregional consequences of the tumor and surgical possibilities. In
      the propitious cases, prenatal MRI examination is useful to precise tumor's
      limits and cerebral status of the foetus. At birth, coordinate management
      involving anaesthetists, paediatricians and specialized surgeons decrease
      morbidity and mortality. Complete early surgical excision must be managed as soon
      as possible and planned thanks to TDM end MRI examination.

PMID- 17030387
TI  - [Efficiency of the combination of Mersilene-musculocutaneous flap in the
      reconstruction of full-thickness chest wall defects. A retrospective study of 14
      cases].
AB  - SUBJECT: The tumors of chest wall can be responsible of large full-thickness
      defects. The skeletal stabilization by different synthetic materials with
      numerous modalities of use and the superficial coverage of the defect by a
      musculocutaneous flap are the two imperatives parts of this reconstruction.
      PATIENTS AND METHODS: From January 1997 to January 2006, 14 patients, 10 males
      and 4 females, aged between 17 and 63 years old and suffering from full-thickness
      chest wall defects secondary to tumor resection have benefited from a simple
      reconstruction, wherever the defect, by a Mersilene Mesh and a muscular or
      musculocutaneous flap. These defects measured between 8 x 12 cm and 14 x 16 cm
      and were located in the anterior part of the chest in 3 cases, with resection of
      the upper half of the sternum and the internal part of both clavicles and the
      first three ribs, and in the lateral part of the chest in 11 cases with resection
      between 3 and 5 ribs. The histological diagnoses of these tumors were 3
      chondrosarcomas, 3 sternum and 1 rib metastases, 2 desmoid tumors, 1 Ewing's
      sarcoma, 4 benign tumors. The flaps used were pedicled in 13 cases and based on
      the latissimus dorsi muscle, the serratus muscle and the pectoralis major muscle;
      in 1 case, the latissimus dorsi musculocutaneous flap was free. RESULTS: The
      skeletal stabilisation seems satisfying. There was no problems with the pulmonary
      function except in 4 cases where a dyspnea appears in sustained effort. No
      vascular complication on these flaps was noted. With a mean follow up of 46
      months, there was no local recurrence of the malignant tumors. Two patients were
      deceased 1 year after surgery.0. CONCLUSION: The Mersilene mesh associated with a
      locoregional musculocutaneous flap represent a simple and efficient solution for
      the treatment of such defects.

PMID- 17030388
TI  - [Pilomatricoma or calcifying epithelioma of Malherbe. A pediatric review of 89
      cases].
AB  - The authors report an exclusive pediatric review of 89 pilomatricomas operated in
      83 patients. This tumor, also known as calcifying epithelioma of Malherbe, is
      common in the pediatric population and occurs mainly on the head and neck region.
      It is a benign skin neoplasm usually misdiagnosed and yet the most common hair
      follicle tumor. The treatment is a surgical excision taking the overlying skin.
      Principal characteristics and clinical presentation of this tumor are discussed.

PMID- 17030389
TI  - [Salvage of a leg avulsion injury by vacuum negative pressure therapy: a case
      report].
AB  - We present the case of a 51-year-old woman who suffered an avulsion injury of the
      right leg in a car accident. In a first time, the simple suture with tiny
      debridement of the flaps is a failure and lead to a nearly complete necrosis. In
      a second time, a total avulsion of the devitalized skin is realised and a
      circumferential VAC system is placed on the wound. Four cycles of vacuum therapy
      and twelve days later, a split-thickness skin mesh-graft is applied on the leg.
      This one has a very good take and allows the patient to stand up one month after
      the initial accident. This example underlines the role of cleaning and pro
      budding of the negative therapy after the salvage of a leg avulsion.

PMID- 17030390
TI  - [Amelanotic malignant melanoma: about three cases].
AB  - The amelanotic melanoma is a rare type of malignant melanoma. The purpose of this
      report is to point out this aspect of melanoma, whose diagnostic delay is
      frequent. We describe one localisation on the penis, rare in this kind of
      melanoma and two cases of the extremities, more frequent localization of the
      amelanotic melanoma. The therapeutic issues and recommendation are similar to the
      classical pigmented malignant melanoma.

PMID- 17030391
TI  - [Hereditary neuropathy with liability to pressure palsies (HNPP) in hand surgery:
      reminds and warn against a usually unrecognised disease].
AB  - Tomacula is a rare hereditary disease due to a deletion on chromosome 17.
      Clinical presentation varies but patients usually complain of recurrent
      paraesthesiaes and palsies related to compression or trauma of a peripheral
      nerve. Diagnosis is based on electrophysiological studies, nerve biopsies and
      genetic tests. Implications for the patient and family members are a genetic
      counselling and some simple preventive measures. Although there is no curative
      treatment for this neuropathy, surgery can be useful for decompression of nerves
      and neurolysis. However, the surgical act increases the risk of nerve damage.
      Knowing about the diagnosis can help the patient and the surgical team avoid
      causing lesions.

PMID- 17030392
TI  - Vanadium distribution, lipid peroxidation and oxidative stress markers upon
      decavanadate in vivo administration.
AB  - The contribution of decameric vanadate species to vanadate toxic effects in
      cardiac muscle was studied following an intravenous administration of a
      decavanadate solution (1mM total vanadium) in Sparus aurata. Although decameric
      vanadate is unstable in the assay medium, it decomposes with a half-life time of
      16 allowing studying its effects not only in vitro but also in vivo. After 1, 6
      and 12h upon decavanadate administration the increase of vanadium in blood
      plasma, red blood cells and in cardiac mitochondria and cytosol is not affected
      in comparison to the administration of a metavanadate solution containing labile
      oxovanadates. Cardiac tissue lipid peroxidation increases up to 20%, 1, 6 and 12h
      after metavanadate administration, whilst for decavanadate no effects were
      observed except 1h after treatment (+20%). Metavanadate administration clearly
      differs from decavanadate by enhancing, 12h after exposure, mitochondrial
      superoxide dismutase (SOD) activity (+115%) and not affecting catalase (CAT)
      activity whereas decavanadate increases SOD activity by 20% and decreases (-55%)
      mitochondrial CAT activity. At early times of exposure, 1 and 6h, the only effect
      observed upon decavanadate administration was the increase by 20% of SOD
      activity. In conclusion, decavanadate has a different response pattern of lipid
      peroxidation and oxidative stress markers, in spite of the same vanadium
      distribution in cardiac cells observed after decavanadate and metavanadate
      administration. It is suggested that once formed decameric vanadate species has a
      different reactivity than vanadate, thus, pointing out that the differential
      contribution of vanadium oligomers should be taken into account to rationalize in
      vivo vanadate toxicity.

PMID- 17030393
TI  - Novel anticonvulsant drugs.
AB  - Principles of complex mechanisms of action of anticonvulsants including latest
      reports concerning new antiepileptic drugs (AED) are considered. Different
      aspects of new anticonvulsant drugs (2nd generation) from preclinical and
      clinical testing, pharmacokinetics, and mono or combination therapy in children
      and adults are summarized. In the following condensed synopsis pharmacological
      and clinical characteristics of gabapentin (GBP), lamotrigine (LTG),
      levetiracetam (LEV), oxcarbazepine (OXC), pregabalin (PGB) and tiagabine (TGB) as
      well as topiramate (TPM) and zonisamide (ZNS) are discussed. In addition to the
      mechanisms of action, pharmacokinetics, interactions, indications and dosages as
      well as side effects are considered. Important data concerning the effect and
      tolerability of anticonvulsant drugs can be obtained from controlled studies. In
      comparison to drugs of the first generation (phenobarbital [PB], primidon [PRD],
      phenytoin [PHT], carbamazepine [CBZ] and valproic acid [VPA]) the potential for
      interactions and side effects due to enzyme induction or inhibition is reduced by
      most of the anticonvulsant drugs of the second generation. New anticonvulsant
      drugs increase the spectrum of treatment and represent further steps with regard
      to the optimization of an individual therapy of the epilepsies.

PMID- 17030394
TI  - Anaesthesia in patients suffering from organophosphorus intoxication-
      interactions between general anaesthetics and acetylcholine in cortical networks
      in vitro.
AB  - In scenarios of mass destruction it is likely that victims are intoxicated by
      organophosphates and, at the same time, physically injured. Organophosphate
      compounds produce excessive cholinergic overstimulation in the CNS via blocking
      acetylcholinesterase activity. The specifics of acute care and anaesthesia in
      physically traumatized and intoxicated patients are largely unknown. Recent
      studies in animals and human subjects demonstrated that acetylcholinesterase
      inhibitors reverse anaesthesia. Two distinct mechanisms are potentially involved.
      First, acetylcholine produces an excitatory drive onto neurons, thereby
      counterbalancing the inhibitory actions of anaesthetics. Anaesthesia is reversed
      because it critically depends on a distinctive depression of several central
      nervous functions. Second, cholinergic stimulation may affect the mechanisms by
      which anaesthetics mediate their depressant actions on central neurons. In this
      case acetylcholine reverses anaesthesia by decreasing the potency of anaesthetic
      agents. In order to identify potential mechanisms involved in cholinergic
      reversal of anaesthesia we have investigated interactions between acetylcholine
      and the volatile anaesthetic sevoflurane in isolated cortical brain slices. Our
      results provide evidence that cholinergic stimulation counterbalances the effects
      of general anaesthetics by increasing neuronal excitability, and, in addition, by
      decreasing anaesthetic potency. These findings imply that in patients suffering
      from organophosphorus intoxication dose requirements for general anaesthetics are
      considerably increased.

PMID- 17030395
TI  - Effect of composite shade, increment thickness and curing light on temperature
      rise during photocuring.
AB  - OBJECTIVES: To examine the effect of composite shade, increment thickness and
      curing light characteristics on the temperature rise associated with composite
      photocuring. METHODS: Four shades (C2, A4, B1 and B3), four sample thicknesses
      (2, 3, 4 and 5 mm) of a hybrid resin composite and two curing units, one with two
      modes of curing, were investigated. The composite samples were packed in
      polytetrafluoroethylene (PTFE) moulds and cured for 40 s. Samples cured with the
      ramp curing mode were irradiated for only 20 s. Temperature rises on the
      undersurface of the curing resin composite were measured using an infrared
      scanning system. RESULTS: Shade C2 produced the highest maximum temperature of
      all shades (56.7 degrees C). Thinner samples produced greater temperature rises
      (2mm induced 60.9 degrees C, 5 mm induced 45.7 degrees C). Samples cured with
      Optilux 501 unit produced greater temperature rises (60.9 degrees C) than those
      cured with Dentsply unit (56.2 degrees C). CONCLUSIONS: There was a quantifiable
      amount of heat generated during visible light curing of resin composite. The
      amount of heat generated was influenced by shade selected, thickness of material
      and characteristics of the light curing unit.

PMID- 17030396
TI  - Assessment of the safety of two ozone delivery devices.
AB  - OBJECTIVES: To evaluate the safety of an ozone gas device designed for use in
      dentistry. METHODS: Two commercially available ozone applicators, Ozi-cure and
      HealOzone were used in a clinical simulation using a phantom head while
      recordings of ozone levels were made in pharyngeal and nasal regions of the
      patient and near the mouth of the operator. Clinical simulations included ozone
      application for caries management and endodontic treatment. Recordings were made
      five times with different levels of suction to assess the effect on ozone levels.
      RESULTS: The results with Ozi-cure on caries mode resulted in a peak ozone level
      in the pharynx of 1.33+/-0.52 ppm when no suction was used. The use of suction
      nearby reduced the ozone level to zero while suction on the opposite side of the
      mouth reduced the level to 0.22+/-0.04 ppm. Used on endodontic mode the peak
      ozone level in the pharynx was 5.51+/-1.63 ppm when no suction was used. The use
      of suction nearby reduced the ozone level to zero while suction on the opposite
      side of the mouth reduced the level to 0.84+/-0.54 ppm. Recordings in the
      patient's nasal region gave a peak of 0.22 ppm when using the Ozi-cure on
      endodontic mode with no suction. At the operator's mouth the ozone level did not
      exceed 0.01 ppm although the characteristic smell of ozone was detectable. All
      recordings with HealOzone were zero. Concentrations of 15 ppm were recorded in a
      simulated tooth cavity with Ozi-cure and >20 ppm with HealOzone. CONCLUSIONS: The
      Ozi-cure device when used without adequate suction allows ozone to be reach a
      concentration above permitted levels and therefore should not be used. The
      HealOzone was safe to use.

PMID- 17030397
TI  - A simple and accurate method for quantification of magnetosomes in magnetotactic
      bacteria by common spectrophotometer.
AB  - A simple apparatus for measuring the magnetism of magnetotactic bacteria was
      developed with a common laboratory spectrophotometer, which was based on
      measuring the change in light scattering resulting from cell alignment in a
      magnetic field. A multiple coils were built around the cuvette holder of the
      spectrophotometer to compensate geomagnetic field and to generate two mutually
      perpendicular magnetic fields. In addition, we defined a novel magnetism
      parameter, R(mag), by modifying the definition of C(mag) to a normalized
      parameter with the culture absorbance obtained without application of magnetic
      field. The number of magnetosomes in each cell was determined by transmission
      electron microscopy to assess the relationship between the two magnetism
      parameters and the distribution of magnetosomes in the cells. We found that both
      R(mag) and C(mag) were linearly correlated rather with the percentage of
      magnetosome-containing bacteria than with the average magnetosome numbers, and
      R(mag) exhibited a better linearity than C(mag) with respect to the percentage of
      magnetosome-containing bacteria.

PMID- 17030398
TI  - Antisociality, underarousal and the validity of the Concealed Information
      Polygraph Test.
AB  - The Concealed Information Polygraph Test has been advocated as the preferred
      method for the physiological detection of deception. In this study, we further
      examined the validity of the Concealed Information Test in antisocial
      individuals. Physiological responding to concealed information was assessed in 48
      male prisoners, and compared with responding in 31 male community volunteers.
      Based upon the association between antisociality and autonomic hyporesponsivity,
      lower detection rates were expected in the prisoners. Participants were
      questioned on five personally significant items (e.g., day of birth), instructed
      to deny recognition of this information, and promised a financial reward when
      able to hide recognition. Prisoners showed reduced autonomic reactivity in
      comparison to the community volunteers. This hyporesponsivity had little impact
      on the sensitivity of the Concealed Information Test. Detection efficiency in the
      prisoners was significantly above chance (d=2.67; a=0.82; 79%), and did not
      differ significantly from that obtained in the community volunteers (d=3.04;
      a=0.85; 87%). The present data support the validity of the Concealed Information
      Test in criminal populations.

PMID- 17030399
TI  - The effects of social stress and cortisol responses on the preconscious selective
      attention to social threat.
AB  - The purpose of the present study was to investigate the effects of social stress
      and stress-induced cortisol on the preconscious selective attention to social
      threat. Twenty healthy participants were administered a masked emotional Stroop
      task (comparing color-naming latencies for angry, neutral and happy faces) in
      conditions of rest and social stress. Stress was induced by means of the Trier
      social stress test. Based on the stress-induced increase in cortisol levels,
      participants were allocated post hoc (median-split) to a high and low responders
      group. In contrast to low responders, high responders showed a negative or
      avoidant attentional bias to threat (i.e. shorter latencies for angry than
      neutral faces) in the rest condition. Most importantly, although low responders
      became avoidant, the high responders became vigilant to the angry faces after
      stress induction. There were no such effects for happy faces. Our findings are in
      line with previous studies in both animals and humans, that associate high
      glucocorticoid stress-responsiveness with diminished avoidance and prolonged
      freezing reactions during stress.

PMID- 17030400
TI  - Detection and visualization of storm hydrograph changes under urbanization: an
      impulse response approach.
AB  - Urbanization often alters catchment storm responses, with a broad range of
      potentially significant environmental and engineering consequences. At a
      practical, site-specific management level, efficient and effective assessment and
      control of such downstream impacts requires a technical capability to rapidly
      identify development-induced storm hydrograph changes. The method should also
      speak specifically to alteration of internal watershed dynamics, require few
      resources to implement, and provide results that are intuitively accessible to
      all watershed stakeholders. In this short paper, we propose a potential method
      which might satisfy these criteria. Our emphasis lies upon the integration of
      existing concepts to provide tools for pragmatic, relatively low-cost
      environmental monitoring and management. The procedure involves calibration of
      rainfall-runoff time-series models in each of several successive time windows,
      which sample varying degrees of watershed urbanization. As implemented here, only
      precipitation and stream discharge or stage data are required. The readily
      generated unit impulse response functions of these time-series models might then
      provide a mathematically formal, yet visually based and intuitive, representation
      of changes in watershed storm response. Nominally, the empirical response
      functions capture such changes as soon as they occur, and the assessments of
      storm hydrograph alteration are independent of variability in meteorological
      forcing. We provide a preliminary example of how the technique may be applied
      using a low-order linear ARX model. The technique may offer a fresh perspective
      on such watershed management issues, and potentially also several advantages over
      existing approaches. Substantial further testing is required before attempting to
      apply the concept as a practical environmental management technique; some
      possible directions for additional work are suggested.

PMID- 17030401
TI  - Estimation of terrestrial chemical spill risk factors using a modified Delphi
      approach.
AB  - The large number of chemical spills each year in the United States presents a
      potentially significant risk to human health and the environment. In an effort to
      manage this risk, the authors are developing a screening tool to assess the
      immediate threat to human and environmental receptors from land-based chemical
      spills. As part of this development effort, a modified Delphi survey was employed
      to determine the most important factors governing this risk and the relative
      importance of these factors. Results of the survey indicate that accounting for
      the attributes of the spilled chemical as well as the characteristics of the
      surrounding environment is imperative in making informed decisions regarding
      spill planning and mitigation. Survey results further indicate the greatest
      concern during spill events to be the risk to human health, which must be
      considered directly as well as factored into decisions concerning the protection
      of environmental receptors.

PMID- 17030402
TI  - The effect of landfill leachate composition on organics and nitrogen removal in
      an activated sludge system with bentonite additive.
AB  - A pre-denitrification activated sludge system (AS) without internal recycle was
      used in lab-scale studies of landfill leachate treatment. A bentonite supplement
      at a ratio of 1:4 (mineral : biomass) was used to ensure high sludge settling
      levels and to serve as a micro-organisms carrier. The system was operated within
      different parameters such as hydraulic retention time (HRT), ammonia loading rate
      (ALR) or external recycle ratio, which was adapted to treat varying leachate
      concentrations of COD and ammonia, ranging from 1020 to 2680 mgO(2)l(-1) and 400
      890 mgNH(4)-Nl(-1) respectively. The nitrification was complete and ammonia
      oxidation reached 99%; this was obtained while the ALR did not exceed 0.09 g
      NH(4)(+)-Ng(-1)MLVSS d(-1) and HRT was not lower than 1 day (in the aeration
      reactor). The performance of denitrification was successfully improved by
      controlling the external recycle rate, when the BOD(5)/N ratio in the raw
      leachate was 4.1. Consequently, N-removal of up to 80% was achieved. A 10-fold
      decrease in the denitrification rate was obtained at a BOD(5)/N ratio of 0.5. The
      efficiency of COD removal varied significantly from 36% to 84%. The positive
      effect of bentonite addition was determined and is discussed based on preliminary
      studies. The experiments were carried out in fill-and-draw activated sludge with
      bentonite; the biomass ratio was 1:2. The activated sludge with bentonite was fed
      with a synthetic high ammonia and organic-free medium.

PMID- 17030403
TI  - The effect of model structure and data in modeling land conditions in disturbed
      complex ecosystems.
AB  - Off-road vehicles increase soil erosion by reducing vegetation cover and other
      types of ground cover, and by changing the structure of soil. The investigation
      of the relationship between disturbance from off-road vehicles and the intensity
      of the activities that involve use of vehicles is essential for water and soil
      conservation and facility management. Models have been developed in a previous
      study to predict disturbance caused by off-road vehicles. However, the effect of
      data on model quality and model performance, and the appropriate structure of
      models have not been previously investigated. In order to improve the quality and
      performance of disturbance models, this study was designed to investigate the
      effects of model structure and data. The experiment considered and tested: (1)
      two measures of disturbance based on the Vegetation Cover Factor (C Factor) of
      the Revised Universal Soil Loss Equation (RUSLE) and Disturbance Intensity; (2)
      model structure using two modeling approaches; and (3) three subsets of data. The
      adjusted R-square and residuals from validation data are used to represent model
      quality and performance, respectively. Analysis of variance (ANOVA) is used to
      identify factors which have significant effects on model quality and performance.
      The results of the ANOVA show that subsets of data have significant effects on
      both model quality and performance for both measures of disturbance. The ANOVA
      also detected that the C Factor models have higher quality and performance than
      the Disturbance models. Although modeling approaches are not a significant factor
      based on the ANOVA tests, models containing interaction terms can increase the
      adjusted R-squares for nearly all tested conditions and the maximum improvement
      can reach 31%.

PMID- 17030404
TI  - Analysis of livelihood security: a case study in the Kali-Khola watershed of
      Nepal.
AB  - This paper examines household livelihoods in highland and lowland communities of
      the Kali-Khola agricultural watershed in western Nepal on the basis of economic,
      ecological and social security indicators. Significant differences were found in
      soil fertility status, pests and diseases management, risk and uncertainties, use
      of agrochemicals and access to social services. No remarkable variations were
      found in crop diversification, annual agricultural income and food sufficiency.
      However, uncertainty and risk in agricultural production is relatively low in
      highland communities. The findings reveal that agriculture production alone is
      not a viable livelihood option for agricultural watershed communities in Nepal.
      The households growing crops with hired labour have relatively sustainable
      livelihoods in Nepal's agricultural watersheds. Insufficient agricultural land,
      insufficient working manpower within a family, and lack of access to ecological
      agricultural services are prime factors in being livelihood insecure in
      agricultural watershed communities. Therefore, long-term policies and plans need
      to be developed for the empowerment of local farmers and to support rural
      livelihoods with adaptable and flexible income-generating strategies, resilient
      resource management institutions and enhancement of knowledge, skills and social
      capital.

PMID- 17030405
TI  - Coeliac disease and risk of mood disorders--a general population-based cohort
      study.
AB  - BACKGROUND: Earlier research has indicated a positive association between coeliac
      disease (CD) and some mental disorders. Studies on CD and depression have
      inconsistent findings and we know of no study of CD and the risk of bipolar
      disorder (BD). METHODS: We used Cox regression to investigate the risk of
      subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD
      and 66,815 age- and sex-matched reference individuals in a general population
      based cohort study in Sweden. We also studied the association between prior MD
      and CD through conditional logistic regression. RESULTS: CD was associated with
      an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6
      2.2; p<0.001, based on 181 positive events in individuals with CD and 529
      positive events in reference individuals). CD was not associated with subsequent
      BD (HR=1.1; 95% CI=0.7-1.7; p=0.779, based on 22 and 99 positive events).
      Individuals with prior depression (OR=2.3; 95% CI=2.0-2.8; p<0.001) or prior BD
      (OR=1.7; 95% CI=1.2-2.3; p=0.001) were at increased risk of a subsequent
      diagnosis of CD. LIMITATIONS: Study participants with CD and MD may have more
      severe disease than the average patient with these disorders since they were
      identified through a hospital-based register. CONCLUSIONS: CD is positively
      associated with subsequent depression. The risk increase for CD in individuals
      with prior depression and BD may be due to screening for CD among those with MD.

PMID- 17030406
TI  - Looking back at PCPT: looking forward to new paradigms in prostate cancer
      screening and prevention.
AB  - OBJECTIVES: Provide a critical summary of the latest interpretation of findings
      from the Prostate Cancer Prevention Trial (PCPT). METHODS: Findings from PCPT and
      recently published post-hoc analyses are reviewed. RESULTS: PCPT demonstrated
      that finasteride can reduce the prevalence of prostate cancer, permitted the
      first large-scale assessment of the performance characteristics of prostate
      specific antigen for prostate cancer screening, and identified new-onset erectile
      dysfunction as an early predictor of cardiovascular events. CONCLUSIONS: PCPT has
      and will continue to yield valuable information regarding future strategies for
      prostate cancer prevention and detection, benign prostatic hyperplasia, and other
      matters of public health importance.

PMID- 17030407
TI  - Kinetics of mouse antibody and lymphocyte responses during intranasal vaccination
      with a lipooligosaccharide-based conjugate vaccine.
AB  - We investigated the kinetics of humoral immunity and its related cellular immune
      responses to intranasal (IN) immunization with a detoxified lipooligosaccharide
      (dLOS)-tetanus toxoid (TT) conjugate against nontypeable Haemophilus influenzae
      (NTHi) in mice. IN vaccination with dLOS-TT elicited high titers of LOS-specific
      IgA in nasal washes and IgG in sera during a course of 4 inoculations while high
      titers of TT-specific IgA and IgG were found in sera. A significant increase of
      LOS-specific IgA antibody forming cells (AFCs) was observed in nasopharyngeal
      associated lymphoid tissue (NALT) and nasal passages. However, TT induced broad
      responses with higher numbers of IgA and IgG AFCs found in NALT and nasal
      passages, less but significant IgA AFCs in cervical lymphoid nodes (CLN), spleen,
      and lungs. Phenotypic analysis revealed a significant rise of total B220+ B
      lymphocytes in NALT and CLN, particularly a rise in IgA+/IgM+ cells in the NALT
      after the immunization. The latter result was complied with a significant rise of
      IL-4 but not IFN-gamma positive CD4+ T-lymphocytes in NALT. Analysis of IgG
      antibody subclasses showed that an IgG1 response to both LOS and TT epitopes
      dominated in serum when compared to IgG2a. These kinetic antibody patterns and
      cellular responses may provide useful information regarding to effective mucosal
      vaccines against NTHi infections.

PMID- 17030408
TI  - The linear allometric relationship between total metabolic energy per life span
      and body mass of mammals.
AB  - The aim of this study is to establish and calculate the exact allometric
      relationship between the total metabolic energy per life span and the body mass
      in a wide range of mammals with about six orders of magnitude variation of the
      body mass of animals. The study shows that it exists a linear relationship
      between the total metabolic energy per life span PT(ls) (kJ) and the body mass M
      (kg) of 95 mammals (3 monotremes, Subclass Prototheria, 16 marsupialis (Subclass
      Theria, Infraclass Metatheria) and 76 placentals (Subclass Theria, Infraclass
      Eutheria)) from type: PT(ls)=A(ls)(+)M(1.0511), where P (kJ/day) is the basal
      rate of metabolism and T(ls) (days) is the mean life span of animals. The linear
      coefficient A(ls)(+)=7.158x10(5) kJ/kg is the total metabolic energy, exhausted
      during the life span per 1 kg body mass of the animals. The mean values of the
      total metabolic energy per life span, per unit body mass (A(ls)) for orders from
      Subclass Prototheria and Theria (Infraclass Metatheria) and orders Xenarthra,
      Pholidota, Soricomorpha, Rodentia (Infraclass Eutheria) varied negligible in
      interval (4.656-5.80)x10(5) kJ/kg. The coefficient A(ls) grows from (7.68
      8.36)x10(5) kJ/kg in Lagomorpha and Artiodactyla (Eutheria) to (10.58
      12.64)x10(5) kJ/kg in orders Carnivora, Pinnipeda and Chiroptera (Eutheria).
      A(ls) grows maximum to 18.5x10(5) kJ/kg in Primates. Thus, the values of
      coefficient A(ls) differ maximum four-fold in all orders. Across the all species
      the values of A(ls) are changes about one order of magnitude. Consequently, our
      survey shows that the changes of the body mass, basal metabolic rate and the life
      span of animals are three mutually related parameters, so that the product
      A(ls)=(PT(ls))/M remains relatively constant in comparison to 1 million fold
      difference in body mass and total metabolic energy per life span between mammals.

PMID- 17030410
TI  - Comparison of analytical error and sampling error for contaminated soil.
AB  - Investigation of soil from contaminated sites requires several sample handling
      steps that, most likely, will induce uncertainties in the sample. The theory of
      sampling describes seven sampling errors that can be calculated, estimated or
      discussed in order to get an idea of the size of the sampling uncertainties. With
      the aim of comparing the size of the analytical error to the total sampling
      error, these seven errors were applied, estimated and discussed, to a case study
      of a contaminated site. The manageable errors were summarized, showing a range of
      three orders of magnitudes between the examples. The comparisons show that the
      quotient between the total sampling error and the analytical error is larger than
      20 in most calculation examples. Exceptions were samples taken in hot spots,
      where some components of the total sampling error get small and the analytical
      error gets large in comparison. Low concentration of contaminant, small extracted
      sample size and large particles in the sample contribute to the extent of
      uncertainty.

PMID- 17030409
TI  - The cAMP response element binding protein (CREB) as an integrative HUB selector
      in metazoans: clues from the hydra model system.
AB  - In eukaryotic cells, a multiplicity of extra-cellular signals can activate a
      unique signal transduction system that at the nuclear level will turn on a
      variety of target genes, eliciting thus diverse responses adapted to the initial
      signal. How distinct signals can converge on a unique signalling pathway that
      will nevertheless produce signal-specific responses provides a theoretical
      paradox that can be traced back early in evolution. In bilaterians, the CREB
      pathway connects diverse extra-cellular signals via cytoplasmic kinases to the
      CREB transcription factor and the CBP co-activator, regulating according to the
      context, cell survival, cell proliferation, cell differentiation, pro-apoptosis,
      long-term memory, hence achieving a "hub" function for cellular and developmental
      processes. In hydra, the CREB pathway is highly conserved and activated during
      early head regeneration through RSK-dependent CREB phosphorylation. We show here
      that the CREB transcription factor and the RSK kinase are co-expressed in all
      three hydra cell lineages including dividing interstitial stem cells,
      proliferating nematoblasts, proliferating spermatogonia and spermatocytes,
      differentiating and mature neurons as well as ectodermal and endodermal
      myoepithelial cells. In addition, CREB gene expression is specifically up
      regulated during early regeneration and early budding. When the CREB function was
      chemically prevented, the early post-amputation induction of the HyBraI gene was
      no longer observed and head regeneration was stacked. Thus, in hydra, the CREB
      pathway appears already involved in multiple tasks, such as reactivation of
      developmental programs in an adult context, self-renewal of stem cells,
      proliferation of progenitors and neurogenesis. Consequently, the hub function
      played by the CREB pathway was established early in animal evolution and might
      have contributed to the formation of an efficient oral pole through the
      integration of the neurogenic and patterning functions.

PMID- 17030411
TI  - Aerobic digestion of starch wastewater in a fluidized bed bioreactor with low
      density biomass support.
AB  - A solid-liquid-gas, multiphase, fluidized bed bioreactor with low density
      particles was used in this study to treat the high organic content starch
      industry wastewater. The characteristics of starch wastewater were studied. It
      shows high organic content and acidic nature. The performance of a three phase
      fluidized bed bioreactor with low density biomass support was studied under
      various average initial substrate concentrations, by varying COD values (2250,
      4475, 6730 and 8910 mg/L) and for various hydraulic retention times (8, 16, 24,
      32 and 40 h) based on COD removal efficiency. The optimum bed height for the
      maximum COD reduction was found to be 80 cm. Experiments were carried out in the
      bioreactor at an optimized bed height, after the formation of biofilm on the
      surface of low-density particles (density=870 kg/m(3)). Mixed culture obtained
      from the sludge, taken from starch industry effluent treatment plant, was used as
      the source for microorganisms. From the results it was observed that increase in
      initial substrate concentration leads to decrease in COD reduction and COD
      reduction increases with increase in hydraulic retention time. The optimum COD
      removal of 93.8% occurs at an initial substrate concentration of 2250 mg/L and
      for the hydraulic retention time of 24h.

PMID- 17030413
TI  - Phosphate removal using sludge from fuller's earth production.
AB  - This study assesses the phosphate removal capacity and mechanism of precipitation
      or adsorption from aqueous solutions in batch experiments by an industrial sludge
      containing gypsum (CaSO(4).2H(2)O) obtained as a by-product from a fuller's earth
      process. The potential capacity for phosphate removal was tested using various
      solution concentrations, pH values, reaction times, and amount of sludge. The
      maximum phosphate adsorption capacity calculated using the Langmuir equation was
      2.0 g kg(-1). The pH for the maximum adsorption by the sludge was neutral to
      alkaline (pH 7-12). Over 99% of phosphate was removed from a phosphate solution
      of 30 mg L(-1) using 0.15 g of sludge in a 9-h reaction. Sulfate (SO(4)(2-))
      concentration increased with increasing initial phosphate concentration, possibly
      because of dissolution of gypsum and adsorption of both sulfate and phosphate. At
      high phosphate concentration (>1000 mg L(-1)), relative constant concentration of
      Ca(2+) was not consistent with adsorption of the most important phosphate removal
      mechanism. Results suggest that precipitation of calcium phosphate is principally
      responsible for phosphate removal under its high concentration. Agglomerated
      precipitate in the reaction sludge was observed by SEM and identified as brushite
      (CaHPO(4).2H(2)O) by XRD, FT-IR, and DTA. Based on thermodynamic considerations,
      it is suggested that the brushite will readily transform to more stable phases,
      such as hydroxyapatite (Ca(5)(PO(4))(3).OH).

PMID- 17030412
TI  - Synthesis and characterization of a new inorganic cation-exchanger-Zr(IV)
      tungstomolybdate: analytical applications for metal content determination in real
      sample and synthetic mixture.
AB  - An amorphous sample of inorganic cation-exchanger Zr(IV) tungstomolybdate was
      prepared by mixing varying ratios of 0.1M aqueous solution of sodium tungstate
      and 0.1M aqueous solution of sodium molybdate into 0.1M aqueous solution of
      zirconium oxychloride at pH 1. This cation-exchanger was found to have a good ion
      exchange capacity (2.40 mequiv.g(-1) for Na(+)), high thermal and chemical
      stability. A tentative structural formula was proposed on the basis of chemical
      composition, FTIR and thermogravimetric analysis. Distribution coefficients
      (K(d)) values of metal ions in various solvent systems were determined. Some
      important and analytically difficult quantitative binary separations viz. Ni(II)
      Pb(II), Ni(II)-Zn(II), Ni(II)-Cd(II), Mg(II)-Al(III), etc. were achieved. The
      practical applicability of the cation-exchanger was demonstrated in the
      separation of Cu(II)-Zn(II) from a synthetic mixture as well as from real samples
      of pharmaceutical formulation and brass alloy.

PMID- 17030414
TI  - Improving the performance of sequencing batch reactor (SBR) by the addition of
      zeolite powder.
AB  - Two types of operation means "SBR reactor alone (control reactor)" and "adding
      zeolite powder into SBR reactor (test reactor)" were used to treat municipal
      wastewater. The test results revealed that zeolite powder addition could improve
      the activity of the activated sludge. It was investigated the specific oxygen
      utilization rate (SOUR) of the tested zeolite sludge were about double times that
      of the control activated sludge, and the nitrification rate and settling property
      of zeolite-activated sludge were both improved. Due to the combination of zeolite
      adsorption for NH(4)(+)-N and enhanced simultaneous nitrification and de
      nitrification (SND), a higher nitrogen removal was observed in test reactor
      compared to the control reactor, and the addition of zeolite powder is helpful to
      inhabit sludge bulking. In addition, through long-term parallel shock load test,
      it was found that the zeolite powder addition could enhance the ability of
      activated sludge in resisting the shock load of organics and ammonium. Compared
      to the control activated sludge, zeolite powder added activated sludge could
      remove COD, NH(4)(+)-N, TN and TP significantly in a shorter cycle time. At the
      same operational time period, the test SBR could treat wastewater quantity 1.22
      times that treated in control SBR.

PMID- 17030415
TI  - Removal of C.I. Acid Orange 7 from aqueous solution by UV irradiation in the
      presence of ZnO nanopowder.
AB  - The removal of C.I. Acid Orange 7 (AO7) from aqueous solution under UV
      irradiation in the presence of ZnO nanopowder has been studied. The average
      crystallite size of ZnO powder was determined from XRD pattern using the Scherrer
      equation in the range of 33 nm. The experiments showed that ZnO nanopowder and UV
      light had a negligible effect when they were used on their own. The effects of
      some operational parameters such as pH, the amount of ZnO nanopowder and initial
      dye concentration were also examined. The photodegradation of AO7 was enhanced by
      the addition of proper amount of hydrogen peroxide, but it was inhibited by
      ethanol. From the inhibitive effect of ethanol, it was deducted that hydroxyl
      radicals played a significant role in the photodegradation of the dye. The
      kinetic of the removal of AO7 can be explained in terms of the Langmuir
      Hinshelwood model. The values of the adsorption equilibrium constant, K(AO7), and
      the kinetic rate constant of surface reaction, k(c), were 0.354(mg l(-1))(-1) and
      1.99 mg l(-1)min(-1), respectively. The electrical energy consumption per order
      of magnitude for photocatalytic degradation of AO7 was lower in the
      UV/ZnO/H(2)O(2) process than that in the UV/ZnO process. Accordingly, it could be
      stated that the complete removal of color, after selecting desired operational
      parameters could be achieved in a relatively short time, about 60 min.

PMID- 17030416
TI  - Potential use of a combined ozone and zeolite system for gaseous toluene
      elimination.
AB  - This study investigated the performance of a combined ozone and zeolite system in
      eliminating gaseous toluene which is a major contaminant in many industrial and
      indoor environments. The hypothesis that the removal of toluene by ozone can be
      substantially affected by confining the oxidation reaction in a zeolite structure
      was evaluated. The degradation of toluene seemed to be contributed by the active
      oxygen atom generated from the decomposition of ozone at the Lewis acid sites in
      the zeolite 13X. Air containing toluene levels at 1.5, 2 and 3 ppm was injected
      with ozone in the range of 0-6 ppm before being vented into a fixed amount of
      3600 g zeolite 13X with 90 mm bed-length. The experimental results showed that
      the elimination rate of toluene was significantly enhanced when compared to using
      zeolite or ozone alone. In particular, over 90% of the 1.5 ppm toluene was
      removed when 6 ppm ozone was used at 40% relative humidity level. Deactivation of
      the zeolite 13X after a few hours of reactions under the current experimental
      conditions was probably due to the adsorbed water, carbon dioxide and the
      reaction by-products. The residue species left in the zeolite and the
      intermediate species in the exhaust gas stream were characterized by FT-IR, GC-MS
      and HP-LC methods, respectively. A distinctive peak of O atom attached to the
      Lewis acid site at 1380 cm(-1) was found in the FT-IR spectrum and trace amount
      of aldehydes was found to be the reaction by-products.

PMID- 17030417
TI  - Hexavalent chromium removal from wastewater using aniline formaldehyde condensate
      coated silica gel.
AB  - A resinous polymer, aniline formaldehyde condensate (AFC) coated on silica gel
      was used as an adsorbent in batch system for removal of hexavalent chromium from
      aqueous solution by considering the effects of various parameters like reaction
      pH, dose of AFC coated silica gel, initial Cr(VI) concentration and aniline to
      formaldehyde ratio in AFC synthesis. The optimum pH for total chromium [Cr(VI)
      and Cr(III)] adsorption was observed as 3. Total chromium adsorption was second
      order and equilibrium was achieved within 90-120 min. Aniline to formaldehyde
      ratio of 1.6:1 during AFC synthesis was ideal for chromium removal. Total
      chromium adsorption followed Freundlich's isotherm with adsorption capacity of 65
      mg/g at initial Cr(VI) 200mg/L. Total chromium removal was explained as
      combinations of electrostatic attraction of acid chromate ion by protonated AFC,
      reduction of Cr(VI) to Cr(III) and bond formation of Cr(III) with nitrogen atom
      of AFC. Almost 40-84% of adsorbed chromium was recovered during desorption by
      NaOH, EDTA and mineral acids. AFC coated silica gel can be effectively used for
      treatment of chromium containing wastewaters as an alternative.

PMID- 17030418
TI  - Predicting pressure drop in venturi scrubbers with artificial neural networks.
AB  - In this study a new approach based on artificial neural networks (ANNs) has been
      used to predict pressure drop in venturi scrubbers. The main parameters affecting
      the pressure drop are mainly the gas velocity in the throat of venturi scrubber
      (V(g)(th)), liquid to gas flow rate ratio (L/G), and axial distance of the
      venturi scrubber (z). Three sets of experimental data from five different venturi
      scrubbers have been applied to design three independent ANNs. Comparing the
      results of these ANNs and the calculated results from available models shows that
      the results of ANNs have a better agreement with experimental data.

PMID- 17030419
TI  - Heavy metal leaching from aerobic and anaerobic landfill bioreactors of co
      disposed municipal solid waste incineration bottom ash and shredded low-organic
      residues.
AB  - In this study, heavy metal leaching from aerobic and anaerobic landfill
      bioreactor test cells for co-disposed municipal solid waste incineration (MSWI)
      bottom ash and shredded low-organic residues has been investigated. Test cells
      were operated for 1 year. Heavy metals which were comparatively higher in
      leachate of aerobic cell were copper (Cu), lead (Pb), boron (B), zinc (Zn),
      manganese (Mn) and iron (Fe), and those apparently lower were aluminum (Al),
      arsenic (As), molybdenum (Mo), and vanadium (V). However, no significant release
      of heavy metals under aerobic conditions was observed compared to anaerobic and
      control cells. Furthermore, there was no meaningful correlation between oxidation
      reduction potential (ORP) and heavy metal concentrations in the leachates
      although some researchers speculate that aeration may result in excessive heavy
      metal leaching. No meaningful correlation between dissolved organic carbon (DOC)
      and leaching of Cu and Pb was another interesting observation. The only heavy
      metal that exceeded the state discharge limits (10mg/l, to be enforced after
      April 2005) in the aerobic cell leachate samples was boron and there was no
      correlation between boron leaching and ORP. Higher B levels in aerobic cell
      should be due to comparatively lower pH values in this cell. However, it is
      anticipated that this slightly increased concentrations of B (maximum 25mg/l)
      will not create a risk for bioreactor operation; rather it should be beneficial
      for long-term stability of the landfill through faster washout. It was concluded
      that aerobization of landfills of heavy metal rich MSWI bottom ash and shredded
      residues is possible with no dramatic increase in heavy metals in the leachate.

PMID- 17030420
TI  - Speciation of Cr(III) and Cr(VI) after column solid phase extraction on Amberlite
      XAD-2010.
AB  - A speciation procedure for Cr(III) and Cr(VI) based on column solid phase
      extraction on Amberlite XAD-2010 and flame atomic absorption spectrometry
      combination. Cr(VI) was quantitatively recovered on Amberlite XAD-2010 resin at
      pH range of 2.0-3.0 as its diethyldithiocarbamate complex, while the recoveries
      of Cr(III) was below 5%. The influences of the various parameters including
      amounts of the reagents, eluent type and its volume, sample volume, etc., on the
      quantitative recoveries were examined. The interference of matrix and coexistent
      elements for method were studied. The detection limit (corresponding to three
      times the standard deviation of the blank) and the enrichment factor for Cr(VI)
      were found to be 1.28 microg/L and 25, respectively. To verify the accuracy of
      the method, drinking water certified reference material (CRM-TMDW-500) was
      analyzed and the results obtained were in good agreement with the certified
      value. The proposed method has been successfully applied to the speciation of
      Cr(III) and Cr(VI) in water samples and preconcentration of total chromium in
      environmental samples.

PMID- 17030422
TI  - Adsorption of p-nitrophenol from aqueous solutions onto activated carbon fiber.
AB  - The adsorption of p-nitrophenol (PNP) onto activated carbon fiber (ACF) was
      investigated in simulated wastewater in a batch system to evaluate the effects of
      solution pH, presence of sodium chloride, adsorbent doses and temperature. It was
      found that PNP adsorption amount depended on pH, sodium chloride content,
      adsorbent doses and temperature. Langmuir and Freundlich models were applied to
      describe the adsorption isotherms. Freundlich model agreed with experimental data
      well, indicating the possibility of more than just one monomolecular layer of
      coverage. SEM photographs of ACF before and after adsorption revealed that it was
      in part with multimolecular layers of coverage on ACF surfaces. The change of
      free energy, enthalpy, and entropy of adsorption were also evaluated for the
      adsorption process. The pseudo-first-order and pseudo-second-order kinetic models
      were used to describe the kinetic data. The experimental data fitted very well
      the pseudo-second-order kinetic model. Attempts were made to desorb PNP from ACF
      using dilute NaOH solution and water, and desorption efficiency was obtained to
      the extent of 92.7% with 0.025 M NaOH and water at 368 K.

PMID- 17030421
TI  - Sorption kinetics and chemical forms of Cd(II) sorbed by thiol-functionalized 2:1
      clay minerals.
AB  - The interaction between Cd(II) in aqueous solution and two 2:1 expandable clay
      minerals (i.e., montmorillonite and vermiculite), showing different layer charge,
      was addressed via batch sorption experiments on powdered clay minerals both
      untreated and amino acid (cysteine) treated. Reaction products were characterized
      via X-ray powder diffraction (XRDP), chemical analysis (elemental analysis and
      atomic absorption spectrophotometry), thermal analysis combined with evolved
      gases mass spectrometry (TGA-MSEGA) and synchrotron-based X-ray absorption
      spectroscopy via extended X-ray absorption fine structure (EXAFS)
      characterization. Sorption isotherms for Cd(II) in presence of different
      substrates, shows that Cd(II) uptake depends both on Cd(II) starting
      concentration and the nature of the substrate. Thermal decomposition of Cd
      cysteine treated clay minerals evidences the evolution of H(2)O, H(2)S, NO(2),
      SO(2), and N(2)O(3). These results are well consistent with XRDP data collected
      both at room and at increasing temperature and further stress the influence of
      the substrate, in particular cysteine, on the interlayer. EXAFS studies suggest
      that Cd(II) coordinates with oxygen atoms, to give monomer complexes or CdO
      molecules, either on the mineral surface and/or in the interlayer. For Cd
      cysteine complexes EXAFS data agree with the existence of Cd-S clusters, thus
      suggesting a predominant role of the thiol group in the bonding of Cd with the
      amino acid.

PMID- 17030423
TI  - Distribution of copper in the vicinity of a deactivated mining site at Carajas in
      the Amazon region of Brazil.
AB  - In this work the re-fixation of mobilized copper (Cu) that was released from a
      deactivated pilot Cu ore dressing plant in the tropical rain forest at
      Southeastern Amazon (Carajas) was studied. Samples of top soils, decay leaf
      litter deposited on soils, roots and leaves of standing biomass were taken for
      the determination of Cu concentration in order to evaluate the distribution of it
      between different environmental compartments. In the sampling points near to the
      now extinct plant, total Cu concentrations in the soil reached an average value
      of 2140 microg g(-1) above the natural level of about 40 microg g(-1), being that
      bioavailable Cu estimated by DTPA method varied from 1.9 to 20.7% of this total.
      From the data was possible to calculate that the soil compartment is able to hold
      around 10 kg Cu/m(2) of ground. Roots of the standing biomass in that area hold
      around 17 g Cu/m(2), while the Cu content in leaves showed to be largely
      independent of the Cu level in the soil. Copper in the leaves was estimated as
      around 1g/m(2) of ground area. In turn, the decay leaf litter deposited on soil
      can hold about 1.6 g Cu/m(2). The terrestrial system surrounding the abandoned
      pilot plant demonstrated great buffer capacity to retain mobile Cu released by
      anthropogenic activities in the area.

PMID- 17030424
TI  - Degradation of hexachlorobenzene by electron beam irradiation.
AB  - Hexachlorobenzene removal efficiencies in different solvents by electron beam
      irradiation were investigated. Several factors that might affect the removal
      efficiencies were further examined. At 10 kGy, HCB degradation value was 85.8% in
      the solvent of acetone:water mixture (20:80, v/v), while at the same dose, the
      reduction value of 42.6% was achieved in hexane solvent. In the solvent of
      acetone:water mixture (20:80, v/v), Na(2)CO(3) as additive could enhance the
      degradation efficiency by 4.5%. However, Triton X-100, NaNO(3), NaNO(2) and
      H(2)O(2) as additives reduced the degradation value by 20.0%, 6.3%, 85.7% and
      20.5%, respectively. Furthermore, the increase of these additives would result in
      the decrease of the degradation efficiencies. The pH value of the solvent of
      acetone:water mixture (20:80, v/v) could affect HCB removal efficiency. At pH
      11.8, reduction value of 90.2% was achieved at 10 kGy, while at the same dose, at
      pH 2.7 and 6.8, the reduction values were only 82.4% and 86.9%, respectively. At
      the same time, the degradation value of pentachlorobenzene was 94.7% at 10 kGy.
      In the presence or absence of additives, pH value of the solvent of acetone:water
      mixture (20:80, v/v) became lower with increasing dose after electron beam
      irradiation.

PMID- 17030425
TI  - The removal of Cu(II) and Co(II) from aqueous solutions using cross-linked
      chitosan--evaluation by the factorial design methodology.
AB  - A 2(3) factorial design was employed to evaluate the quantitative removal of
      Cu(II) and Co(II) on glutaraldehyde-cross-linked chitosan from kinetic isotherms,
      using chitosan masses of 100 and 300mg and temperatures of 25 and 35 degrees C.
      The adsorption parameters were analyzed statistically using modeling polynomial
      equations and a cumulative normal probability plot. The results indicated the
      higher quantitative preference of the chitosan for Cu(II) in relation to Co(II).
      Increasing the chitosan mass decreases the adsorption/mass ratio (mol g(-1)) for
      both metals. The principal effect of the temperature did not show statistical
      importance. The adsorption thermodynamic parameters, namely Delta(ads)H,
      Delta(ads)G and Delta(ads)S, were determined. Exothermic and endothermic results
      were found in relation to a specific factorial design experiment. A comparison of
      Delta(ads)H values was made in relation to some metal-adsorbent interactions in
      literature. It is suggested that the adsorption thermodynamic parameters are
      determined by the influence of the principal and interactive experimental
      parameters and not by the temperature changes alone.

PMID- 17030426
TI  - The use of slurry sampling for the determination of manganese and copper in
      various samples by electrothermal atomic absorption spectrometry.
AB  - Manganese and copper in multivitamin-mineral supplements and standard reference
      materials were determined by slurry sampling electrothermal atomic absorption
      spectrometry. Slurries were prepared in an aqueous solution containing Triton X
      100. The effects of different parameters such as ratio of solid to liquid phase
      volume, total slurry volume and addition of Triton X-100 as a dispersant on the
      analytical results were investigated. The graphite furnace programs were
      optimized for slurry sampling depending on the analytes and their concentrations
      in the samples. The linear calibration method with aqueous standard solutions was
      used for the quantification. At optimum experimental conditions, R.S.D. values
      were below 5%. The analytes were determined in the limits of 95% confidence level
      with respect to certified values in coal and soil standard reference materials
      and to those found by wet-digestion in multivitamin-mineral supplements.
      Detection limits (3delta) for Mn and Cu were 0.10 microg L(-1) and 1.82 microg L(
      1) for 10 microL coal standard reference material slurry, respectively.

PMID- 17030427
TI  - Sulphur mustard vapor breakthrough behaviour on reactive carbon systems.
AB  - Breakthrough behaviour of sulphur mustard, the deadliest of persistent chemical
      warfare agents, on carbon systems such as NaOH/CrO(3)/C, NaOH/CrO(3)/EDA/C and
      RuCl(3)/C has been studied and the data were compared with that of active carbon.
      Effects of bed lengths of carbons on breakthrough time have also been correlated.
      Thereafter, the effects of flow rate of air-sulphur mustard mixture,
      concentration and temperature on the kinetic parameters such as rate constant
      (k(v)) and kinetic saturation capacity (W(e)) were analyzed and interpreted by
      means of modified Wheeler equation. Rate constant was found to be increasing
      while W(e) was found to be invariable with the increase in air flow rate. Both
      k(v) and W(e) decreased with the increase of temperature, however, no significant
      effect on W(e) and k(v) was observed due to concentration change (0.3-0.6 mg/l).
      The values of kinetic saturation capacity were used to predict the service
      lives/breakthrough times of carbon beds (when used in filtration systems).

PMID- 17030428
TI  - Region-specific regulation of inflammation and pathogenesis in experimental
      autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple
      sclerosis and is characterized by an infiltrate of predominantly T cells and
      macrophages in the spinal cord and brain. In both the spinal cord and the
      cerebellum, Th1 cells direct inflammation to antigen-rich white matter tracts,
      and there is a TNFR1-dependent recruitment of CD11b(hi) cells in both regions. In
      the spinal cord, parenchymal invasion, demyelination and clinical symptoms are
      associated with TNFR1-dependant parenchymal induction (especially astrocytes) of
      VCAM-1 and CXCL2. None of these events occur in the cerebellum despite the fact
      that an inflammatory infiltrate accumulates in the perivascular space. Therefore
      regional specificity in astrocyte responses to inflammatory cytokines may
      regulate regional parenchymal infiltration and pathogenesis.

PMID- 17030429
TI  - Targeting adenosine A2A receptors in Parkinson's disease.
AB  - The adenosine A2A receptor has emerged as an attractive non-dopaminergic target
      in the pursuit of improved therapy for Parkinson's disease (PD), based in part on
      its unique CNS distribution. It is highly enriched in striatopallidal neurons and
      can form functional heteromeric complexes with other G-protein-coupled receptors,
      including dopamine D2, metabotropic glutamate mGlu5 and adenosine A1 receptors.
      Blockade of the adenosine A2A receptor in striatopallidal neurons reduces
      postsynaptic effects of dopamine depletion, and in turn lessens the motor
      deficits of PD. A2A antagonists might partially improve not only the symptoms of
      PD but also its course, by slowing the underlying neurodegeneration and reducing
      the maladaptive neuroplasticity that complicates standard 'dopamine replacement'
      treatments. Thus, we review here a prime example of translational neuroscience,
      through which antagonism of A2A receptors has now entered the arena of clinical
      trials with realistic prospects for advancing PD therapeutics.

PMID- 17030430
TI  - Genetic mouse models for studying inhibitors of spinal axon regeneration.
AB  - The laboratory mouse has emerged as a primary model organism for studying axon
      regeneration after experimental spinal cord injury, owing to its genetic
      amenability. Mutant mouse models are contributing significantly to our
      understanding of the molecular mechanisms of axon regeneration failure in the
      adult mammalian central nervous system (CNS), in particular regarding the role of
      axon-growth inhibitors. Here, we discuss recent advances in understanding axon
      regeneration failure that have been made using genetically modified mice,
      focusing on the inhibitory influences in the CNS, and we illustrate the
      advantages of using the mouse as a surrogate organism to study axon regeneration
      and spinal cord repair.

PMID- 17030431
TI  - Molecular programming of stem cells into mesodiencephalic dopaminergic neurons.
AB  - In a screen for homeobox transcription factors expressed in the embryonic ventral
      midbrain, Andersson et al. recently identified Lmx1a and Msx1. Using in ovo
      electroporation in chick embryos, they showed that these factors are crucial for
      initiating the differentiation of neuroepithelial progenitor neurons into
      mesodiencephalic dopaminergic (mdDA) neurons. Lmx1a also initiated a
      developmental program that drove an mdDA phenotype in mouse embryonic stem cells.
      This indicates that these factors can be exploited in cell-replacement strategies
      for treatment of Parkinson's disease.

PMID- 17030432
TI  - Intracellular messengers involved in spontaneous pain, heat hyperalgesia, and
      mechanical allodynia induced by intrathecal dihydroxyphenylglycine.
AB  - We investigated the role of two intracellular second messengers, extracellular
      signal-regulated protein kinase (ERK) and protein kinase C (PKC), in a model of
      persistent pain using intrathecal (i.t.) (R,S)-3,5-dihydroxyphenylglycine (DHPG).
      Spontaneous nociceptive behaviours (SNBs), mechanical allodynia (von Frey
      thresholds) and heat hyperalgesia (plantar test latencies) induced by DHPG were
      measured in animals pretreated i.t. with membrane permeable inhibitors of ERK (PD
      98059) and PKC (GF 109203X). Spinal administration of PD 98059 dose-dependently
      reduced SNBs, and attenuated both mechanical allodynia and heat hyperalgesia
      induced by DHPG. GF 109203X treatment also reduced SNBs and heat hyperalgesia,
      but did not affect mechanical allodynia induced by DHPG. Neither PD 98059, nor GF
      109203X, altered mechanical or thermal thresholds in saline-injected control
      rats. These results suggest that both ERK and PKC are involved in persistent pain
      associated with the i.t. administration of DHPG.

PMID- 17030433
TI  - Antioxidant N-acetylcysteine inhibits the activation of JNK3 mediated by the
      GluR6-PSD95-MLK3 signaling module during cerebral ischemia in rat hippocampus.
AB  - Cerebral ischemia induces kainate receptor glutamate receptor 6 (GluR6) binding
      to the postsynaptic density protein 95 (PSD95), which in turn anchors mixed
      lineage kinase 3 (MLK3) via SH3 domain in rat brain. MLK3 subsequently activates
      c-Jun NH(2)-terminal kinase (JNK) via MAP kinase kinases (MKKs). In this study,
      we investigated the association of PSD95 with GluR6 and MLK3, the
      autophosphorylation of MLK3, the combination of MLK3 with JNK3, and the
      phosphorylation of JNK3 during cerebral ischemia in rat hippocampus CA1. Our
      results indicate that the GluR6-PSD95-MLK3 complex quickly enhanced at 5 min of
      ischemia and peaked at 10 min of ischemia, and then gradually reduced with the
      prolonged time of ischemia. Interestingly, the combination of MLK3 and JNK3
      gradually increased from 5 min to 30 min of ischemia. JNK3 phosphorylation first
      increased and then attenuated in cytosol, suggesting the translocation of
      activated JNK3 to nucleus during ischemia. To further investigate the possible
      mechanism of JNK3 activation, antioxidant N-acetylcysteine (NAC) was given to the
      rats 20 min prior to ischemia. Results indicate that NAC distinctly inhibited the
      association of PSD95 with GluR6 and MLK3, the autophosphorylation of MLK3, the
      combination of MLK3 with JNK3 and JNK3 activation. Taken together, these finding
      indicate that ischemic stimulation results in JNK3 activation through the GluR6
      PSD95-MLK3 signaling module, and that the activation of JNK3 is closely related
      to oxidative stress.

PMID- 17030434
TI  - Severity level and injury track determine outcome following a penetrating
      ballistic-like brain injury in the rat.
AB  - Penetrating ballistic brain injury (PBBI) is a high-energy transfer wound causing
      direct damage to the cerebrum. Outcome is directly related to the ballistic's
      anatomical path and degree of energy transfer. In this study we evaluated
      differences in outcome induced by altering the 'projectile' paths and severity
      levels of a simulated bullet wound using a newly characterized rat model of PBBI.
      Severity levels (5, 10, and 15%) were compared across three distinct injury
      paths: (1) unilateral 'frontal', (2) 'bilateral' hemispheric, and (3) unilateral
      'caudal' (including cerebellum/midbrain). Outcome was assessed by differences in
      mortality rate and motor dysfunction (e.g. neurological and balance beam
      deficits). Results indicated that outcome was dependent not only on the severity
      level of PBBI (P<0.001, r=0.535) but also brain regions injured (P<0.001,
      r=0.398). A unilateral caudal injury was associated with the highest degree of
      mortality (up to 100%) and motor dysfunction (64-100% disability). Bilateral
      hemispheric injuries were also potentially fatal, while the best outcomes were
      associated with a unilateral frontal injury (no mortality and 14-39% motor
      disability). These data closely resemble clinical reports of ballistic wounds to
      the head and further validate the rat PBBI model with the ultimate intent to
      investigate novel therapeutic approaches for diagnosis and treatment of the
      neuropathological damage associated with PBBI.

PMID- 17030435
TI  - Participation of peripheral group I and II metabotropic glutamate receptors in
      the development or maintenance of IL-1beta-induced mechanical allodynia in the
      orofacial area of conscious rats.
AB  - The present study investigated the role of peripheral groups I and II
      metabotropic glutamate receptors (mGluRs) in interleukin (IL)-1beta-induced
      mechanical allodynia in the orofacial area of rats. Subcutaneous injection of 10
      pg of IL-1beta decreased air-puff thresholds ipsilateral or contralateral to the
      injection site. The decrease in air-puff thresholds appeared 10 min after the
      injection of IL-1beta and IL-1beta-induced mechanical allodynia persisted for
      over 3 h. Pre-treatment with 7-(hydroxyimino) cyclopropa[b] chromen-1a
      carboxylate ethyl ester (CPCCOEt) or 2-methyl-6-(phenylethynyl)-pyridine
      hydrochloride (MPEP), a mGluR1 or mGluR5 antagonist, blocked IL-1beta-induced
      mechanical allodynia and mirror-image mechanical allodynia produced by a
      subcutaneous injection of 10 pg of IL-1beta. However, post-treatment with CPCCOEt
      or MPEP did not affect changes in behavioral responses, which were produced by
      the IL-1beta injection. Pre-treatment, as well as post-treatment with (2R,4R)-4
      aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGluR agonist, blocked
      either IL-1beta-induced mechanical allodynia or mirror-image mechanical
      allodynia. The anti-allodynic effects of APDC were abolished by pre-treatment
      with (2S)-2-amino-2[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic
      acid (LY341495), a group II mGluR antagonist. These results indicate that
      peripheral group II mGluRs are involved in the development and maintenance of IL
      1beta-induced mechanical allodynia, while peripheral group I mGluRs are involved
      in the development of IL-1beta-induced mechanical allodynia. Based on our
      observations, the peripheral application of group II mGluR agonists may be of
      therapeutic value in treating inflammatory pain.

PMID- 17030436
TI  - Intracellular location of the ABC transporter PRP1 related to pentamidine
      resistance in Leishmania major.

PMID- 17030438
TI  - Pain relief by applying transcutaneous electrical nerve stimulation (TENS) on
      acupuncture points during the first stage of labor: a randomized double-blind
      placebo-controlled trial.
AB  - Transcutaneous electrical nerve stimulation (TENS) is one of the non
      pharmacological means of pain relief for labor and delivery. We aimed to
      investigate the efficacy and safety of TENS on specific acupuncture points for
      reducing pain in the first stage of labor. In this double-blind, placebo
      controlled trial, we randomly assigned healthy full-term parturients in active
      phase of first-stage labor to either TENS on four acupuncture points (Hegu [Li 4]
      and Sanyinjiao [Sp 6]) (n=52) or the TENS placebo (n=53). Visual analogue scale
      (VAS) was used to assess pain before and 30 and 60 min after treatment. The
      primary outcome was the rate of VAS score decrease 3 in each group. A
      questionnaire was given at 24h post-partum to evaluate the satisfaction of pain
      relieving method and the willingness to have the same treatment again. Mode of
      delivery and neonatal effect were measured as secondary outcome. One hundred
      women were eligible for analysis. TENS group experienced VAS score reduction 3
      significantly more common than the TENS placebo group (31/50 [62%] vs 7/50 [14%],
      P<0.001). Willingness of using the same analgesic method for a future childbirth
      was also significantly different (TENS: 48/50 [96%] vs TENS placebo: 33/50 [66%],
      P<0.001). Operative delivery was increased in the TENS group (12/50 [24%] vs 4/50
      [8%], P=0.05), but the neonatal outcomes were not different. The application of
      TENS on specific acupuncture points could be a non-invasive adjunct for pain
      relief in the first stage of labor.

PMID- 17030437
TI  - Activity-dependent slowing of conduction velocity in uninjured L4 C fibers
      increases after an L5 spinal nerve injury in the rat.
AB  - Growing evidence suggests that uninjured afferents may play an important role in
      neuropathic pain following nerve injury. The excitability of nociceptive neurons
      in the L4 spinal nerve appears to be enhanced following an injury to the adjacent
      L5 spinal nerve. In this study, we investigated whether the action-potential
      conduction properties of unlesioned, unmyelinated fibers are also altered. A
      teased-fiber technique was used to record from single C fibers from the L4 spinal
      nerve of the rat in vitro. Repeated electrical stimulation of the tibial nerve
      was used to investigate activity-dependent slowing of conduction velocity. Twin
      pulse stimulation at a 50 ms interpulse interval allowed investigation of
      supranormal conduction velocity. Blinded experiments were performed 8-10 days
      after sham surgery and after an L5 spinal nerve ligation (L5 SNL). Activity
      dependent slowing revealed two populations of C fibers, a "nociceptor" population
      with a large degree of activity-dependent slowing and a "non-nociceptor"
      population with a smaller degree of activity-dependent slowing. Both populations
      showed enhanced activity-dependent slowing of conduction velocity and enhanced
      supranormal conduction velocities in lesioned animals compared to sham animals.
      Activity-dependent slowing was also enhanced after an L5 SNL in the mouse. These
      alterations in conduction velocity may reflect changes in expression of ion
      channels responsible for the membrane excitability. These data provide additional
      evidence that a nerve injury leads to persistent alterations in the properties of
      adjacent uninjured, unmyelinated fibers.

PMID- 17030439
TI  - Comparison of vibration perception thresholds in individuals with diffuse upper
      limb pain and carpal tunnel syndrome.
AB  - The study objective was to compare vibration perception and patterns of blood
      flow in outpatients with diffuse upper limb pain disorder (ULPD), carpal tunnel
      syndrome (CTS) and age and sex matched healthy controls. Vibration perception and
      discrimination thresholds were compared in subjects with ULPD (n=27), CTS (n=27)
      and healthy matched controls (n=54). Vibration measurements were taken
      bilaterally at three sites: (a) over the dorsum of the second and (b) fifth
      metacarpals and (c) the palmar aspect of the first and second metacarpals,
      corresponding to the innervation territories of the radial, ulnar and median
      nerves, respectively. Non-invasive assessments of peripheral blood flow were also
      performed in both limbs. When compared to healthy controls, subjects with ULPD
      had widespread elevation of vibration thresholds both ipsilateral and
      contralateral to the symptomatic limb. Subjects with CTS had similarly elevated
      vibration thresholds at sites both adjacent to and distant from the site of
      peripheral nerve injury. The responses to cold pressor testing of the upper limbs
      were physiologically normal in both the CTS and ULPD patient groups. Furthermore,
      there were no significant differences in the haemodynamic responses between the
      patient groups. The global elevation of vibration thresholds in subjects with
      both ULPD and CTS is consistent with altered central nervous system mechanisms,
      common to both conditions, which may be either adaptive to or maintaining the
      perception of pain.

PMID- 17030440
TI  - EFTEM assistant: a tool to understand the limitations of EFTEM.
AB  - The first version of a free tool for Gatan's Digital Micrographtrade mark is
      presented which aims to aid the energy-filtered TEM (EFTEM) community by
      predicting and correcting the most common sources of degradation. The software
      allows selection of either Krivanek's or Egerton's approach to account for the
      spatial resolution degradation caused by the electron optical aberrations. The
      effects of aberrations and signal 'delocalization' are combined to simulate the
      blurring caused in EFTEM elemental maps. Two microstructural features with ideal
      geometry are used to illustrate use of the software: spherical particles and
      parallel sided interfaces. The software also allows the simulation of the effects
      of the noise and drift in the final elemental map, independently or in
      combination. It can be easily demonstrated that when the dimensions of the
      feature of interest are comparable in scale to the image degradation factors, the
      effects of the latter should not be neglected. More importantly, the software can
      deconvolute the effects of the degradation factors, revealing the true dimensions
      and signal intensity of the feature of interest.

PMID- 17030441
TI  - Alpha,beta-dicarbonyl reduction by Saccharomyces D-arabinose dehydrogenase.
AB  - An alpha,beta-dicarbonyl reductase activity was purified from Saccharomyces
      cerevisiae and identified as the cytosolic enzyme D-Arabinose dehydrogenase
      (ARA1) by MALDI-TOF/TOF. Size exclusion chromatography analysis of recombinant
      Ara1p revealed that this protein formed a homodimer. Ara1p catalyzed the
      reduction of the reactive alpha,beta-dicarbonyl compounds methylglyoxal,
      diacetyl, and pentanedione in a NADPH dependant manner. Ara1p had apparent Km
      values of approximately 14 mM, 7 mM and 4 mM for methylglyoxal, diacetyl and
      pentanedione respectively, with corresponding turnover rates of 4.4, 6.9 and 5.9
      s(-1) at pH 7.0. pH profiling showed that Ara1p had a pH optimum of 4.5 for the
      diacetyl reduction reaction. Ara1p also catalyzed the NADP+ dependant oxidation
      of acetoin; however this back reaction only occurred at alkaline pH values. That
      Ara1p was important for degradation of alpha,beta-dicarbonyl substrates was
      further supported by the observation that ara1-Delta knockout yeast mutants
      exhibited a decreased growth rate phenotype in media containing diacetyl.

PMID- 17030442
TI  - Plant peroxisomes as a source of signalling molecules.
AB  - Peroxisomes are pleiomorphic, metabolically plastic organelles. Their essentially
      oxidative function led to the adoption of the name 'peroxisome'. The dynamic and
      diverse nature of peroxisome metabolism has led to the realisation that
      peroxisomes are an important source of signalling molecules that can function to
      integrate cellular activity and multicellular development. In plants defence
      against predators and a hostile environment is of necessity a metabolic and
      developmental response--a plant has no place to hide. Mutant screens are
      implicating peroxisomes in disease resistance and signalling in response to
      light. Characterisation of mutants disrupted in peroxisomal beta-oxidation has
      led to a growing appreciation of the importance of this pathway in the production
      of jasmonic acid, conversion of indole butyric acid to indole acetic acid and
      possibly in the production of other signalling molecules. Likewise the role of
      peroxisomes in the production and detoxification of reactive oxygen, and possibly
      reactive nitrogen species and changes in redox status, suggests considerable
      scope for peroxisomes to contribute to perception and response to a wide range of
      biotic and abiotic stresses. Whereas the peroxisome is the sole site of beta
      oxidation in plants, the production and detoxification of ROS in many cell
      compartments makes the specific contribution of the peroxisome much more
      difficult to establish. However progress in identifying peroxisome specific
      isoforms of enzymes associated with ROS metabolism should allow a more definitive
      assessment of these contributions in the future.

PMID- 17030443
TI  - Comparative proteomic analysis reveals differential expression of Hsp25 following
      the directed differentiation of mouse embryonic stem cells.
AB  - Murine embryonic stem (ES) cells can be committed to neural differentiation with
      high efficiency in culture through the use of feeder- and serum-free media. This
      system is proving to be an excellent model to study processes involved in ES cell
      commitment to neural cell fate. We used this approach to generate neurogenic
      embryoid bodies (NEBs) in a serum-free culture system to perform proteomic
      analysis of soluble fractions and identify early changes in protein expression as
      ES cells differentiate. Ten candidate proteins were altered significantly in
      expression levels. One of the most significant alterations was for the small heat
      shock protein Hsp25. Three species of Hsp25 are detected in ES cells, and this
      expression pattern changes during the first 24 h of differentiation until
      expression is decreased to levels that are barely detectable at 4 days following
      differentiation. We used immunofluorescence studies to confirm that following ES
      cell differentiation, expression of Hsp25 becomes excluded from neural precursors
      as well as other differentiating cells, making it a potentially useful marker of
      early ES cell differentiation.

PMID- 17030444
TI  - Diverse functions of p120ctn in tumors.
AB  - p120ctn is a member of the Armadillo protein family. It stabilizes the cadherin
      catenin adhesion complex at the plasma membrane, but also has additional roles in
      the cytoplasm and nucleus. Extensive alternative mRNA splicing and multiple
      phosphorylation sites generate additional complexity. Evidence is emerging that
      complete loss, downregulation or mislocalization of p120ctn correlates with
      progression of different types of human tumors. It remains to be determined
      whether a causal relationship exists between specific isoform expression,
      subcellular localization or selective phosphorylation of p120ctn on the one hand
      and tumor prognosis on the other.

PMID- 17030445
TI  - Formation of peroxisomes: present and past.
AB  - Eukaryotic cells contain functionally distinct, membrane enclosed compartments
      called organelles. Here we like to address two questions concerning this
      architectural lay out. How did this membrane complexity arise during evolution
      and how is this collection of organelles maintained in multiplying cells to
      ensure that new cells retain a complete set of them. We will try to address these
      questions with peroxisomes as a focal point of interest.

PMID- 17030446
TI  - Elevated circulating oxidized LDL levels in Japanese subjects with the metabolic
      syndrome.
AB  - In the present study, we examined the relationship between circulating oxidized
      low-density lipoprotein (LDL) and the metabolic syndrome in Japanese patients.
      Subjects who had no histories of coronary or peripheral artery disease and were
      taking no medications (n=119; age 57+/-10 years; male/female, 90:29) underwent a
      complete history and physical examination, determination of blood chemistries and
      oxidized LDL levels. In stepwise regression analysis, triglycerides (p=0.0001)
      and HDL-cholesterol (p=0.0493, inversely) were independently correlated to
      oxidized LDL levels. Furthermore, a significant association (p<0.0001) was found
      between circulating oxidized LDL levels and the accumulation of the number of the
      components of the metabolic syndrome. Oxidized LDL levels were one of the
      independent determinants of intima-media thickness of the common carotid artery,
      a surrogate marker of atherosclerosis. The present study reveals that circulating
      oxidized LDL levels are strongly associated with the metabolic syndrome. Our
      results suggest that elevation of oxidized LDL may be a possible molecular link
      between accelerated atherosclerosis and the metabolic syndrome in Japanese
      subjects.

PMID- 17030447
TI  - Smoking expectancies for flavored and non-flavored cigarettes among college
      students.
AB  - Several tobacco companies have introduced specially flavored cigarettes, yet
      little is known about their appeal among college student nonsmokers, regular
      smokers, and those susceptible to smoking. Undergraduates (N=424) rated 12 brands
      of cigarettes on multiple attributes based on manufacturer advertisements. This
      paper focused on two brands with flavored and non-flavored versions (Camel and
      Salem). Despite brand, regular smokers and those susceptible to smoking
      initiation had higher positive expectancies and lower negative expectancies about
      smoking than nonsmokers. Flavored cigarettes elicited higher positive
      expectancies than non-flavored counterparts across all groups, including
      nonsmokers. Indeed, the degree to which flavored Camels had higher positive
      expectancies than Camel Lights was at least as large in a group of susceptible
      nonsmokers and experimenters (susceptible/experimenters). Despite being present
      in nonsmokers and susceptible/experimenters, negative expectancies were
      significantly lower for flavored versus non-flavored brands. Logistic regressions
      revealed that positive expectancies predicted "intention to try" each brand for
      regular smokers and susceptible/experimenters. These findings suggest that
      targeting the marketing of positive attributes may be useful in preventing
      smoking behavior.

PMID- 17030449
TI  - Inflammation in variant angina: is there any evidence?
AB  - Variant angina, defined as spontaneous angina pectoris associated with transient
      ST-segment elevation, has proved to be caused usually by episodic coronary spasm
      since Prinzmetal and his associates described a form of angina quite different
      from classic Heberden angina pectoris in 1959. Currently, coronary artery spasm
      is defined as reversible coronary stenosis, which limits coronary blood flow
      under resting conditions, and it plays an important role in ischemic heart
      disease, particularly in variant angina. Data available in respect of coronary
      vasospasm showed that it is closely related to atherosclerotic coronary artery
      disease, since intravascular ultrasound studies reveal atherosclerotic plaques in
      almost any spastic segment. Risk factors for coronary artery disease and coronary
      vasospasm, however, differ profoundly. Cigarette smoking is the only established
      risk factor. Although several candidates and predisposing factors, such as
      serotonin, histamine, thromboxane, and endothelin, have been described, the
      mediators and the pathogenesis of the disease remain unknown. There are abundant
      studies that inflammation plays an important role in the initiation, development
      as well as evolution of atherosclerosis, suggesting that atherosclerosis is an
      inflammation disease. The evidence regarding the role of inflammatory pathways in
      different clinical entities of coronary artery disease has significantly been
      accumulated. And also, primary studies have showed that inflammation may be a
      contributor for variant angina or vasospastic coronary disease is at least
      partially driven by inflammation. Although much more research is obviously
      needed, primary evidence provide us with some direction for that research.

PMID- 17030450
TI  - A circadian model for viral persistence.
AB  - Persistently infecting DNA viruses depend heavily on host cell DNA synthesis
      machinery. Replication of cellular and viral DNA is inhibited by mutagenic
      stress. It is hypothesized that diurnal regulation of viral DNA replication may
      occur at the level of cell cycle checkpoints and DNA repair, to protect DNA from
      exposure to UV light or other mutagens. This highly conserved mechanism is traced
      back to viruses that persist in prokaryotes and eukaryotes. Inhibition of viral
      DNA replication and the cell cycle in response to UV light may represent a
      functional building block in the evolution of circadian-gated DNA replication.
      Viral DNA replication appears to be closely linked to the circadian clock by
      interaction of viral promoters, early viral proteins and transcription factors.
      It is proposed here that under certain conditions viral oncogene expression is
      phase-shifted relative to that of tumor suppressor and DNA repair genes. The
      resulting desynchrony of checkpoint controls and DNA repair from diurnal
      genotoxic exposure produces cyclic periods of suboptimal response to DNA damage.
      This temporal vulnerability to genotoxic stress produces a "mutator phenotype"
      with inherent genome instability. The proposed model delineates areas of research
      with implications for viral pathogenesis and therapeutics.

PMID- 17030448
TI  - The tyrosine kinase inhibitor genistein blocks HIV-1 infection in primary human
      macrophages.
AB  - Binding of HIV-1 envelope glycoprotein (Env) to its cellular receptors elicits a
      variety of signaling events, including the activation of select tyrosine kinases.
      To evaluate the potential role of such signaling, we examined the effects of the
      tyrosine kinase inhibitor, genistein, on HIV-1 entry and infection of human
      macrophages using a variety of assays. Without altering cell viability, cell
      surface expression of CD4 and CCR5 or their abilities to interact with Env,
      genistein inhibited infection of macrophages by reporter gene-encoding, beta
      lactamase containing, or wild type virions, as well as Env-mediated cell-fusion.
      The observation that genistein blocked virus infection if applied before, during
      or immediately after the infection period, but not 24h later; coupled with a more
      pronounced inhibition of infection in the reporter gene assays as compared to
      both beta-lactamase and p24 particle entry assays, imply that genistein exerts
      its inhibitory effects on both entry and early post-entry steps. These findings
      suggest that other exploitable targets, or steps, of the HIV-1 infection process
      may exist and could serve as additional opportunities for the development of new
      therapeutics.

PMID- 17030451
TI  - Outbreak of hepatitis C virus infection during sclerotherapy of varicose veins:
      long-term follow-up of 196 patients (4535 patient-years).
AB  - BACKGROUND/AIMS: The aim of this study was to describe the natural history of a
      HCV infection outbreak in 196 patients who had sclerotherapy by a same physician
      and to confirm patient-to-patient transmission using phylogenetic analysis in a
      large series of patients. METHODS: Demographic information included clinical and
      biological parameters. Fibrosis evaluation was performed using liver biopsy or
      transient elastography. Follow-up was maintained until death, or the end of the
      observation period. In order to determine if the virus had been transmitted
      between the HCV genotype 2 patients, sequence analysis was undertaken of a part
      of the NS5b region of the genomes in samples of patients. RESULTS: The mean
      duration of follow-up was 23.1+/-6.7 years (4535 patient-years). In patients with
      fibrosis evaluation, 55.7% had no or mild fibrosis and 44.3% had significant
      fibrosis. No patient died from HCV-related disease. Nucleotide sequence analysis
      of a part of the NS5b region revealed that patients were all infected with the
      same HCV subtype (genotype 2d). The most evident feature of the tree is the
      clustering of all patients involved in the outbreak without any unrelated
      isolates. CONCLUSION: This study emphasizes the risk for nosocomial spread of HCV
      during intravenous therapy.

PMID- 17030452
TI  - Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress.
AB  - This study investigated the effect of thalidomide on oxidative stress in rat
      liver cirrhosis. The cirrhosis of rat was induced by intraperitoneal injection of
      carbon tetrachloride thrice weekly; meanwhile, thalidomide (10mg/kg or 100mg/kg)
      was given daily by intragastric administration for 8 weeks. The content of
      oxidative stress parameters, including superoxide dismutase, glutathione
      peroxidase, and malondialdehyde, in the liver was detected by biochemical assay.
      Immunohistochemistry revealed alpha-smooth muscle actin (alpha-SMA), desmin, and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) protein in the liver. Nuclear
      factor kappa B p65 (NF-kappaBp65) protein in nucleus and transforming growth
      factor beta1 (TGF-beta1) protein in cytoplasm were detected by Western blot. NF
      kappaBp65, TGF-beta1, and TIMP-1 mRNA levels in the liver were studied using
      reverse transcriptase polymerase chain reaction. Liver histopathology was
      significantly improved in rats given high doses of thalidomide. The content of
      oxidative stress parameters and the expressions of NF-kappaBp65, TGF-beta1 and
      TIMP-1 protein, and mRNA were significantly decreased in these animals. The
      expressions of alpha-SMA and Desmin protein were also significantly decreased in
      them. Thalidomide might exert an effect on the inhibition of oxidative stress via
      downregulation of NF-kappaB signaling pathway to prevent the progression of liver
      cirrhosis.

PMID- 17030453
TI  - [Nosocomial respiratory infection due to an imipenem-resistant Pseudomonas
      aeruginosa O: 12 strain in a Tunis's neonatal intensive care unit].
AB  - OBJECTIVE: Investigation of an outbreak caused by an imipenem-resistant
      Pseudomonas aeruginosa strain and research of its hospital reservoir. PATIENTS
      AND METHODS: Nine strains isolated from protected tracheal specimens during 14
      weeks (October 2004 to January 2005) from 8 infants, and one strain from vacuum
      interrupter were studied. Epidemiological study was investigated by determination
      of antibiotics susceptibility, serotyping and Pulsed-field gel electrophoresis
      (PFGE). RESULTS: Strains were of O:12 serotype, they have the same antibiotype
      characterised by imipenem resistance. Strains were indistinguishable or closely
      related as determined by PFGE. The common source of P. aeruginosa O:12 strains
      was not determined, however eradication of the epidemic strain was obtained by
      amelioration of hygiene conditions and the change of disinfectors. CONCLUSION:
      Outbreak of respiratory infections due to an imipenem-resistant P. aeruginosa
      O:12. The common source of the epidemic strain was not determined.

PMID- 17030454
TI  - Genotype MRSA, a new genetic test for the rapid identification of staphylococci
      and detection of mecA gene.
AB  - Early detection of Staphylococcus methicillin resistance (MR) is essential.
      However MR determination may be difficult because it is necessary to perform
      investigation of heterogeneous resistance and low level of resistance and to
      discriminate between oxacillin resistance and borderline resistance. Several
      phenotypic methods are recommended but they fail to detect low level of
      production de PBP2a, the modified Penicillin Binding Protein responsible for MR.
      Detection of mecA gene, the gene encoding PBP2a, using PCR is considered to be
      the reference method. We evaluated Genotype MRSA, a new rapid system based on DNA
      multiplex amplification and further hybridisation, for the identification of
      staphylococci and detection of the mecA gene. The study was performed on a
      collection of various Staphylococcus strains (N=30) from clinical human isolates
      including S. aureus MR and methicillin susceptible (MS), S. epidermidis MR and
      MS, and other species of coagulase negative Staphylococcus (CNS) MR and MS. For
      all the strains, the hybridization banding pattern obtained using Genotype MRSA
      correlated with their expected phenotypic and genotypic characteristics. Genotype
      MRSA allows the identification of the mecA gene as well as S. aureus and S.
      epidermidis specific genes. This DNA strip technology based assay can easily be
      incorporated into routine diagnostics. In addition, the short testing time (less
      than 2 hours) optimises treatment orientation. Genotype MRSA completely complies
      with all requirements for a fast, safe, valid and cost-effective MR diagnosis in
      staphylococci.

PMID- 17030455
TI  - [Mycoplasma pneumoniae infections: retrospective study in Basse-Normandie, 1997
      2005. Epidemiology--diagnostic utility of serology and PCR for a rapid
      diagnostic].
AB  - OBJECTIVES: The objective of this study was to evaluate the epidemiology of
      Mycoplasma pneumoniae (Mpn) infections in Basse-Normandie by a retrospective
      analysis of serological and PCR data, and to confirm the diagnostic utility of
      PCR and serology. METHODS: From 1997 to August 2005, 6156 serum samples and 6123
      respiratory tract samples were collected from hospitalised patients and evaluated
      for the diagnosis of Mpn infection by PCR, serological assays, or by the two
      tests. During the epidemic period (2004-2005), the results of 1489 patients were
      analysed. RESULTS: Over the 9-y period, the seroprevalence was 40,4% and we
      reported on 525 cases with serologically or/and PCR proven Mpn infection,
      according a cyclic pattern spaced out 7 years. During the epidemic period, the
      seroprevalence increased to 50,2% and the rate of infections was 8.3%. The
      analysis of the 124 cases of Mpn infection showed typical epidemiological
      characteristics: a peak of incidence among the children and young adults, a
      summer-winter pattern and some coinfections with viral strains. For diagnosis of
      Mpn infection, the comparison of PCR and serological assays among 36 patients
      showed a concordance of only 41.7%. CONCLUSION: Mpn infections were endemic and
      outbreaks were observed according cyclic pattern with a high incidence specially
      in the children. Sensitive and specific tests were now available for early and
      reliable diagnosis. In children, the combination of the PCR on nasopharyngeal
      samples and the IgM EIA serology test were recommended. In adults, the PCR was
      privilegiated.

PMID- 17030456
TI  - [Antimicrobial susceptibility of Proteus mirabilis urinary tract isolates from
      1999 to 2005 at Nimes University Hospital].
AB  - AIM OF THE STUDY: To analyse antimicrobial resistance trends of Proteus mirabilis
      urinary tract isolates from 1999 to 2005 at the Nimes University hospital.
      MATERIALS AND METHODS: We retrospectively collected non-duplicate urinary tract
      infections and colonization isolates from inpatients between 1 January 1999 and
      31 December 2005. RESULTS: One thousand and eight non-duplicate urinary tract
      isolates were studied, 63.1% were from females and the mean age was 76 years. The
      mean resistance rate was 59.0% for amoxicillin (AMX), 48.0% for piperacillin
      (PIP), 3.9% for cefotaxim, 33.9% for amoxicillin plus clavulanic acid (AMC) and
      2.8% for piperacillin plus tazobactam (TZP). A significant increase in resistance
      was observed for AMC and TZP. The mean resistance rate was 35.0% for norfloxacin,
      34.8% for ofloxacin and 23.5% for ciprofloxacin. No significant increase in
      resistance to fluoroquinolones was seen except for ciprofloxacin whereas a
      significant increase was observed for aminoglycosides. The mean rate resistance
      for cotrimoxazole was 33.2% with a significant decrease in the resistance during
      the study period. CONCLUSION: P. mirabilis stilled sensitive to cefotaxim or
      ceftazidim and to TZP. The significant increase in the rate resistance to AMC and
      TZP could be explained by production of beta-lactamases and in particular
      extended-spectrum beta-lactamases. The increase in resistance observed for
      fluoroquinolones become a major concern. Amikacine was the most active
      aminoglycosides. These data suggested for the re-enforcement of the antimicrobial
      susceptibility surveillance in order to optimise the rational use of antibiotics.

PMID- 17030457
TI  - [Early detection of hepatitis C virus infection using a new combined antigen
      antibody detection assay: potential use in HIV co-infected individuals].
AB  - BACKGROUND: The aim of this study was to determine the clinical benefit of a new
      combined antigen-antibody immunoenzymatic assay (Monolisa HCV Ag-Ab Ultra,
      Biorad) in the setting of acute HCV infection in HIV infected patients. PATIENTS
      AND METHODS: The performance of this assay was first evaluated in 160 HIV
      positive samples from uninfected and chronically HCV infected patients. To assess
      the performance of the Ag-Ab assay in the context of acute hepatitis C, 94 stored
      frozen serums from 20 recently diagnosed cases were retrospectively tested for
      HCV-RNA and presence of anti-HCV antibodies, in parallel with the new assay.
      RESULTS: In HIV infected patients, the sensitivity and specificity of the Ultra
      assay was 100% with a strong discrimination between positive and negative
      samples. In HCV acutely infected patients, the Ag-Ab assay significantly reduced
      the seronegative period, allowing an earlier diagnosis compared to a 3rd
      generation ELISA in 65% of the cases. The combined assay became positive on the
      same bleed as the first HCV-RNA detection for 13 patients out of 20.
      Nevertheless, in one case, characterized by an absence of seroconversion over one
      year but a continuous viral replication above 1 million IU/ml, the combined assay
      did not improve HCV infection diagnosis. CONCLUSION: Use of this new assay as a
      first line screening would significantly reduce the long seronegative window
      period seen in HCV infection allowing earlier HCV diagnosis and rapid clinical
      management. However, in case of clinical acute hepatitis C, sensitive HCV-RNA
      detection should remain the gold standard.

PMID- 17030458
TI  - [Extended-spectrum betalactamases producing Escherichia coli: a new health-care
      associated infection threat?].
AB  - OBJECTIVES: Study the health-care associated infection risk due to Extended
      Spectrum Betalactamases Producing Escherichia coli (ESBL Esc) isolated from
      diagnostic samples. METHODS: Descriptive, longitudinal and prospective study of
      104 diagnostic isolates of ESBL Esc, one per patient, identified in Amiens
      university hospital between February 1999 and December 2005. Patients (sex, age,
      contamination risk factor, antecedent hospitalization) and microbiological data
      were progressively collected, entered into EPI INFO 6.04dFr software (ENSP,
      France) database, and compared using the chi-square test and Wilcoxon rank sum
      test, as appropriate. A p value of less than 0.05 was considered significant.
      RESULTS: Diagnostic ESBL Esc isolates raised, per 1000 isolates of Esc, from 1.2
      in 1999 to 6 in 2005. Global and acquired isolates number of ESBL Esc varied from
      7 and 3 in 2002 to 25 and 19 in 2003 (P=0.22). ESBL Esc global and acquired
      incidence per 10(5) patient-days were, 0.8 and 0.6 in 1999 and 4.99 and 3.4 in
      2005 (P<10(-6)), but rose from 0.6 acquired isolate in 2002 to 3.9 in 2003
      (P=0.002). ESBL Esc, isolated from urines, stools, pulmonary, blood and surgical
      site samples of patients of>/=65 years aged (68.3%), were imipenem and latamoxef
      sensitive. Their acquisition risk factors found were hospitalization during the
      last 6 month period (40/104) and transfer from other institutions (20/104).
      CONCLUSION: ESBL Esc isolates, among ESBL-producing Enterobacteriaceae,
      constitute an escalating health-care associated risk in our institution. The
      research at admission time of ESBL-producing Enterobacteriaceae, mainly in acute
      geriatric wards, strict isolation precaution and hand hygiene observance,
      rational antibiotic usage, are the key actions to control their cross
      transmission. Nonetheless, other studies are needed to determine whether we are
      in front of an ESBL Esc new clone emergence.

PMID- 17030460
TI  - Bacterial aetiology of diarrhoea in young children: high prevalence of
      enteropathogenic Escherichia coli (EPEC) not belonging to the classical EPEC
      serogroups.
AB  - Diarrhoeal disease continues to be one of the most common causes of admittance in
      Children hospital emergency. The aim of the present study was to investigate the
      relative contribution of enteropathogenic and enterohemorrhagic Escherichia coli
      (EPEC and EHEC, respectively) as a cause of infectious bacterial diarrhoea in
      children from the region of Toulouse. We analysed 280 samples of stools from 280
      children (<2 years) with diarrhoea admitted in the "Hopital des Enfants" from
      January to August 2005. Classic pathogens (Salmonella, Campylobacter, Yersinia,
      Shigella, Aeromonas and Vibrio) were detected by standard culture methods.
      Enterotoxigenic Clostridium difficile were identified after culture by immuno
      enzyme assay (IEA). Virulence genes of EPEC and EHEC were detected by using PCR.
      Shiga-toxin production of EHEC strains was confirmed with an IEA test. Potential
      enteric pathogens were identified in 55 patients. EPEC was the most frequently
      identified agent (30 patients), followed by Campylobacter (9 cases: 7 C. jejuni
      and 2 C. coli) and C. difficile (8 patients), then EHEC (5 patients) and
      Salmonella (3 patients). No Shigella, Yersinia, Aeromonas or other pathogenic
      bacteria were detected during this period in that class of children. EPEC not
      belonging to the classical EPEC serogroups were highly prevalent (24 versus 6).
      EHEC possessed different genotypes and serogroups: O26 (2 strains), O157 (2
      strains) and one un-typable strain. This study demonstrates the importance of
      EPEC (55 % of positive cases) and of EHEC (more frequent than Salmonella) in the
      aetiology of diarrhoeal diseases of young children. We confirm the usefulness of
      the PCR methodology: it allows the detection of virulent E. coli and thus
      increases by two fold the diagnosis of bacterial diarrhoea.

PMID- 17030459
TI  - [Performance of different methods of oxacillin resistance detection in atypic
      strains of Staphylococcus aureus].
AB  - Seventy-three of aminoglycoside-susceptible methicillin-resistant Staphylococcus
      aureus (AS-MRSA) and 12 kanamycin-tobramycin-resistant methicillin-susceptible S.
      aureus (KTR-MSSA) isolates were phenotypically and genotypically examined for
      methicillin susceptibility. The AS-MRSA profile represents 8.3% of MRSA strains
      and the KTR-MSSA profile represents 1.38% of MSSA strains. The diffusion method
      using the 5 microg oxacillin and 30 microg cefoxitin discs on Mueller-Hinton Agar
      (MHA) with and without NaCl, the incubation at 35 degrees C or 30 degrees C for
      24 or 48 hours respectively, and the determining oxacillin MICs by E-test (AES,
      Combourg, France) were performed and used as phenotypic methods. We also used the
      mecA gene PCR which was considered as the "gold standard" for methicillin
      resistance detection, and the Slidex MRSA Detection (bioMerieux) that detect the
      presence of mecA gene product (PBP 2a). To increase the level of PBP 2a
      expression, the 30 microg cefoxitin disc was used as an inducer. All the AS-MRSA
      strains (100%) were detected by the cefoxitin disc in all conditions and by the
      oxacillin disc on MHA with 2% of NaCl at 35 degrees C. Without NaCl, the
      sensitivity fell to 97,2% by oxacillin disc. The oxacillin MICs for these
      isolates ranged from 2 to 128 mg/l. The mecA gene determinant and its product PBP
      2a were detected in all AS-MRSA strains. All KTR-MSSA strains were phenotypically
      methicillin-susceptible and oxacillin MICs were below or borderline of breakpoint
      (< or =2 mg/l). The mecA gene determinant and its product were detected in one
      strain which was considered to be the most heterogeneous of those tested.

PMID- 17030461
TI  - Carbonic anhydrase IX expression is associated with tumor progression and a poor
      prognosis of lung adenocarcinoma.
AB  - Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into
      carbonic acid and participates in a variety of physiological and biological
      processes. The aim of this study was to evaluate the prognostic significance of
      CA IX expression in patients with lung adenocarcinoma. Standard
      immunohistochemical techniques were used to study CA IX expression in 134
      patients who underwent curative resection for adenocarcinoma of the lung at our
      hospital between January 1995 and December 1996. We evaluated the correlations
      between CA IX expression levels on cancer cells and clinicopathological factors.
      CA IX expression was not observed in normal lung tissue or specimens from non
      invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%)
      invasive adenocarcinoma cases. Poor differentiated histological phenotype
      (p=0.0015), pathological stage (p=0.0400), vascular invasion (p=0.0009) and
      lymphatic permeation (p=0.0050) were significantly related to CA IX expression.
      On univariate analysis, CA IX positive cases showed significantly shorter overall
      survival (p=0.0083) and disease-free survival (p=0.0122). In particular, the
      overall and disease-free survivals in stages I+II were significantly shorter in
      the CA IX positive than in the CA IX negative cases (p=0.0269 and 0.0011,
      respectively). Our results suggest that CA IX expression is strongly associated
      with tumor progression and indicates a poor prognosis for patients with stages
      I+II lung adenocarcinoma.

PMID- 17030462
TI  - DNA methylation in reptiles.
AB  - Very recent investigations have provided evidence for a higher DNA methylation
      level in polar and sub-antarctic fishes compared to temperate/tropical fishes,
      the latter being in turn higher than the DNA methylation level of warm-blooded
      vertebrates. These results confirm and extend the finding [Jabbari, K., Caccio,
      S., Pais de Barros, J.P., Desgres, J., Bernardi G., 1997. Evolutionary changes in
      CpG and methylation levels in the genome of vertebrates. Gene 205, 109-118] that
      DNA methylation level of vertebrates is inversely related to body temperature.
      Here we studied the methylation level of reptilian genomes. The species
      previously analyzed exhibited methylation levels closer to those of mammals and
      birds rather than to those of fishes and amphibians. The sample was, however, too
      small to reach a final conclusion. Here we used Reversed-Phase-High-Performance
      Liquid Chromatography (RP-HPLC) to analyze the DNA methylation levels of 43
      reptiles representing three out of four orders and 20 families. Such analysis has
      shown that snakes and lizards exhibit methylation levels covering the whole range
      comprised between those of temperate/tropical fish and mammals, while turtles,
      and, more so, crocodiles are close to mammals. We discuss some ecological and
      physiological data that explain these results.

PMID- 17030463
TI  - Transport of sulfadiazine in soil columns: experiments and modelling approaches.
AB  - Antibiotics, such as sulfadiazine, reach agricultural soils directly through
      manure of grazing livestock or indirectly through the spreading of manure or
      sewage sludge on the field. Knowledge about the fate of antibiotics in soils is
      crucial for assessing the environmental risk of these compounds, including
      possible transport to the groundwater. Transport of (14)C-labelled sulfadiazine
      was investigated in disturbed soil columns at a constant flow rate of 0.26 cm h(
      1) near saturation. Sulfadiazine was applied in different concentrations for
      either a short or a long pulse duration. Breakthrough curves of sulfadiazine and
      the non-reactive tracer chloride were measured. At the end of the leaching period
      the soil concentration profiles were determined. The peak maxima of the
      breakthrough curves were delayed by a factor of 2 to 5 compared to chloride and
      the decreasing limbs are characterized by an extended tailing. However, the
      maximum relative concentrations differed as well as the eluted mass fractions,
      ranging from 18 to 83% after 500 h of leaching. To identify relevant sorption
      processes, breakthrough curves of sulfadiazine were fitted with a convective
      dispersive transport model, considering different sorption concepts with one, two
      and three sorption sites. Breakthrough curves can be fitted best with a three
      site sorption model, which includes two reversible kinetic and one irreversible
      sorption site. However, the simulated soil concentration profiles did not match
      the observations for all of the used models. Despite this incomplete process
      description, the obtained results have implications for the transport behavior of
      sulfadiazine in the field. Its leaching may be enhanced if it is frequently
      applied at higher concentrations.

PMID- 17030464
TI  - Detection of Helicobacter spp. DNA in the oral cavity of dogs.
AB  - The mode of acquisition of gastric Helicobacter spp. infection in dogs has not
      been determined. It is suspected that oral-oral and faecal-oral transmission may
      be involved. The present study sought to determine if Helicobacter spp. DNA is
      present in the oral cavity of healthy and vomiting dogs. Thirty-eight pet dogs
      (27 vomiting and 11 clinically healthy) were studied. The presence of
      Helicobacter spp. was determined by single and nested PCR evaluation of DNA
      extracted from saliva, dental plaque and gastric biopsy samples. Helicobacter
      spp. DNA was detected by nested PCR in 36 (94.7%) gastric biopsies, 17 (44.7%)
      dental plaque and 19 (50%) saliva samples out of the 38 dogs examined. Overall 27
      (71.1%) dogs screened by nested PCR were found to harbour Helicobacter spp. DNA
      in the oral cavity (dental plaque and/or saliva). There was no significant
      difference in the prevalence of Helicobacter spp. DNA in the oral cavity of
      vomiting and healthy dogs, and the time from vomiting to oral sampling did not
      have significant impact. This study confirms the high prevalence of gastric
      Helicobacter spp. infection in dogs, and reveals that Helicobacter spp. DNA is
      detectable in the oral cavity of over 70% of dogs. These findings support the
      possibility of oral-oral transmission between dogs and that the canine oral
      cavity may act as source of non-pylori Helicobacter spp. infection for humans.

PMID- 17030465
TI  - Bradykinin release and inactivation in brain of rats submitted to an experimental
      model of Alzheimer's disease.
AB  - The kallikrein-kinin system is involved in a variety of physiological and
      pathological processes. Components of this system, identified in rat and human
      brains, can be altered in neurodegenerative processes such as Alzheimer's
      disease. Here, we studied kinin release and its inactivation in rats submitted to
      chronic cerebroventricular infusion of beta-amyloid (Abeta) peptide.
      Neurodegeneration was confirmed by histological analysis of brain samples. In
      cerebrospinal fluid of animals infused with Abeta, bradykinin concentration was
      increased, as determined by radioimmunoassay. However, in the brain of Abeta
      group, we only detected the tripeptide Arg-Pro-Pro, purified by reversed-phase
      chromatography and characterized by liquid chromatography-electrospray ionization
      mass spectrometry. This fragment of bradykinin indicated the possible
      participation of kinin-processing enzymes in the brain such as a prolyl
      oligopeptidase.

PMID- 17030466
TI  - Toxicokinetics of 1,1,1,2-tetrafluoroethane (HFC-134a) in male volunteers after
      experimental exposure.
AB  - The aim of this study was to determine the uptake and disposition of inhaled
      1,1,1,2-tetrafluoroethane (HFC-134a) in humans. Ten male volunteers were exposed
      to 500 ppm HFC-134a (2 h, 50 W exercise). The HFC-134a levels were monitored in
      blood, exhaled air and urine up to 19 h post-exposure. The concentration in blood
      increased rapidly, reaching a plateau of 9.4+/-1.9 microM (mean+/-S.D.) within 30
      min, followed by a fast post-exposure decrease. HFC-134a in expired air decreased
      rapidly as well and in parallel with that in blood. The post-exposure urinary
      excretion was 0.002% of the inhaled amount, and the half-time was 58 min (pooled
      data). A physiologically based toxicokinetic (PBTK) model was developed for
      further analysis. Experimental and simulated time courses in blood and exhaled
      air agreed well in all 10 subjects. Further, the late decay in blood was
      consistent with a wash-out of HFC-134a from fat tissues, with a half-time of
      114+/-21 min. The simulated relative uptake during exposure was 3.7+/-0.5%. No
      remarkable findings were observed in the electrocardiographic recordings.
      Fibrinogen in plasma increased 1 day after exposure, whereas no effects on C
      reactive protein, serum amyloid A protein, D-dimer or uric acid were seen.
      Further studies are needed to investigate the possible inflammatory response.

PMID- 17030467
TI  - Impact of menopause and hormonal replacement therapy on harmonics-to-noise-ratio
      of the voice.

PMID- 17030469
TI  - Cloning, molecular characterization and expression of ecto-nucleoside
      triphosphate diphosphohydrolase-1 from Torpedo electric organ.
AB  - During synaptic transmission large amounts of ATP are released from pre- and post
      synaptic sources of Torpedo electric organ. A chain reaction sequentially
      hydrolyses ATP to adenosine, which inhibits acetylcholine secretion. The first
      enzyme implicated in this extracellular ATP hydrolysis is an ecto-nucleoside
      triphosphate diphosphohydrolase (E-NTPDase) that dephosphorylates both ATP and
      ADP to AMP. This enzyme has been biochemically characterized in the synaptosomal
      fraction of Torpedo electric organ, having almost equal affinity for ATP as for
      ADP, a fact that pointed to the type-1 NTPDase enzyme. In the present work we
      describe the cloning and molecular characterization of the cDNA for an NTPDase
      from Torpedo marmorata electric organ. The clone, obtained using the RACE-PCR
      technique, contains and open-reading frame of 1506bp and encodes a 502 amino
      acids protein that exhibits high homology with other NTPDases1 from vertebrates
      previously identified, including those of zebrafish and Xenopus, as well as
      human, rat and mouse. Topology analyses revealed the existence of two
      transmembrane regions, two short cytoplasmic tails and a long extracellular
      domain containing five apyrase-conserved regions. Gene expression studies
      revealed that this gene is expressed in all the Torpedo tissues analyzed.
      Finally, activity and cellular localization of the protein encoded by this newly
      cloned cDNA was assessed by heterologous expression experiments involving COS-7
      and HeLa cells.

PMID- 17030470
TI  - Low density porous carrier drug adsorption and release study by response surface
      methodology using different solvents.
AB  - Low density porous carriers are widely used in the pharmaceutical applications.
      Response surface methodology, using 3(2) factorial design was used to study drug
      adsorption on and its release patterns from microporous polypropylene (Accurel MP
      1000) in the absence of additives. Ibuprofen, as model drug, was adsorbed on the
      polymer by solvent evaporation using two organic solvents methanol (M) and
      dichloromethane (DCM). The amount of carrier (100 mg) and its particle size range
      (250-350 microm) were kept invariant while solvent volume (X1) and drug amount
      (X2) were taken as variables. Drug adsorption pattern depended on the type and
      amount of solvent used. DSC, XRD, FTIR and TGA, predict crystalline nature and
      physical form of adsorption. SEM showed the penetration and adsorption of the
      drug in and on the microporous polymer. Accurel MP 1000 had a pore volume of
      1.992 g/cm3 and surface area of 55.9855 m2/g as detected by mercury porosimetery.
      On drug adsorption, pore volume ranged from 0.413 to 1.198 g/cm3 for methanol and
      0.280-0.759 g/cm3 for DCM. Similarly surface area was in the range 38.445-25.497
      m2/g for methanol and 18.710-32.528m2/g for DCM. The drug release was
      investigated in phosphate buffer pH 7.2. All batches showed excellent in vitro
      floating property. Drug release was partial with recovery to complete dependent
      on type and volume of solvent. R2 values relating to bulk density, pore volume,
      surface area and drug release at 60, 120 and 180 min were estimated. Effect of
      solvent properties shows a positive influence on drug adsorption and release.
      Release profiles of some batches could be considered as gastroretentive drug
      delivery system.

PMID- 17030472
TI  - Hippocampal volumes are larger in postmenopausal women using estrogen therapy
      compared to past users, never users and men: a possible window of opportunity
      effect.
AB  - Considerable evidence suggests that estrogen can have neuroprotective effects.
      However, recent results raised important questions regarding the conditions under
      which hormone therapy (HT) following menopause can be beneficial. It has been
      suggested that variables such as time of initiation and duration of HT use are of
      critical importance for beneficial cognitive effects to be observed. The aim of
      the present study was to investigate the potential neuroprotective effects of
      estrogens in aging on brain regions with high levels of estrogen receptors,
      namely the hippocampus (HC) and the amygdala (AG). In order to better
      characterize the punctual and long-term effects of estrogens, we tested
      postmenopausal women currently using estrogen therapy alone (ET), past HT users,
      never users, and men. Age at menses, age at menopause, HT duration and age were
      included as covariates in the analysis. Results demonstrate that women using ET
      had larger left and right HC volumes compared to men, and larger right HC volumes
      compared to past users and never users. Importantly, we found a significant
      negative relationship between ET duration and HC volume in this group. The
      observed effects were region-specific since no significant differences could be
      observed for the AG. In summary, these findings support a treatment duration
      dependent neuroprotective role of estrogen on HC volume in aging.

PMID- 17030473
TI  - Spine tingling polymorphisms--is apolipoprotein E involved in dendritic shape and
      plasticity?

PMID- 17030474
TI  - Loss of spastic paraplegia gene atlastin induces age-dependent death of
      dopaminergic neurons in Drosophila.
AB  - Hereditary spastic paraplegias (HSPs) are human genetic disorders causing
      increased stiffness and overactive muscle reflexes in the lower extremities.
      atlastin (atl) is one of the major genes in which mutations result in HSP. We
      generated a Drosophila model of HSP that has a null mutation in atl. As they
      aged, atl null flies were paralyzed by mechanical shock such as bumping or
      vortexing. Furthermore, the flies showed age-dependent degeneration of
      dopaminergic neurons. These phenotypes were rescued by targeted expression of atl
      in dopaminergic neurons or feeding L-DOPA or SK&F 38393, an agonist of dopamine
      receptor. Our data raised the possibility that one of the causes of HSP disease
      symptoms in human patients with alt mutations is malfunction or degeneration of
      dopaminergic neurons.

PMID- 17030475
TI  - Preliminary evidence that long-term estrogen use reduces white matter loss in
      aging.
AB  - Despite numerous studies showing neurotrophic and neuroprotective effects of
      estrogen in animal models, the long-term effects of estrogen use on brain
      morphology in older women are not known. Thus, we compared ventricular,
      cerebrospinal fluid, white matter, and grey matter volumes estimated from
      magnetic resonance images of postmenopausal women with more than 20 years
      exposure to unopposed estrogen, women who were not on estrogen, and young healthy
      women. Estrogen users had significantly smaller ventricles and greater white
      matter volumes than non-users, but hormone exposure did not affect grey matter
      volumes. Young healthy women had significantly smaller ventricles, less
      cerebrospinal fluid and more grey matter than both groups of older women.
      However, they had comparable white matter volumes to older women on estrogen.
      These findings suggest that long-term estrogen protects against white matter loss
      in aging. This adds to findings from other studies suggesting estrogen is
      neuroprotective of the hippocampus and other regions in older women.

PMID- 17030476
TI  - Ebselen treatment reduces noise induced hearing loss via the mimicry and
      induction of glutathione peroxidase.
AB  - Previous studies indicate that noise induced hearing loss (NIHL) involves a
      decrease in glutathione peroxidase (GPx) activity and a subsequent loss of outer
      hair cells (OHC). However, the cellular localization of this GPx decrease and the
      link to OHC loss are still poorly understood. In this report, we examined the
      cellular localization of GPx (GPx1, GPx 3 and GPx 4) in F-344 rat before and
      after noise exposure and after oral treatment with ebselen, a small molecule
      mimic of GPx activity. Results indicate that GPx1 is the major isoform within the
      cochlea and is highly expressed in cells of the organ of Corti, spiral ganglia,
      stria vascularis, and spiral ligament. Within 5h of noise exposure (4h at 113 dB,
      4-16 kHz), significant OHC loss was already apparent in regions coincident with
      the 8-16 kHz region of the cochlea. In addition, the stria vascularis exhibited
      significant edema or swelling and a decrease in GPx1 immunoreactivity or
      fluorescent intensity. Treatment with ebselen (4 mg/kg p.o.) before and
      immediately after noise exposure reduced both OHC loss and the swelling of the
      stria vascularis typically observed within 5h post-noise exposure. Interestingly,
      GPx1 levels increased in the stria vascularis after noise and ebselen treatment
      vs noise and vehicle-only treatment, and exceeded baseline no noise control
      levels. These data indicate that ebselen acts to prevent the acute loss of OHCs
      and reduces the acute swelling of the stria vascularis by two potential
      mechanisms: one, as a ROS/RNS scavenger through its intrinsic GPx activity, and
      two, as a stimulator of GPx1 expression or activity. This latter mechanism may be
      due to the preservation of endogenous GPx1 from ROS/RNS induced degradation
      and/or the stimulation of GPx1 expression or activity.

PMID- 17030477
TI  - Frequency discrimination of complex tones by hearing-impaired subjects: Evidence
      for loss of ability to use temporal fine structure.
AB  - For normally hearing subjects, thresholds for discriminating the fundamental
      frequency (F0) of a complex tone, F0DLs, increase when the number of the lowest
      harmonic, N, is above eight. A previous study showed that F0DLs were affected by
      component phase for N above 7, and it was argued that the increase in F0DLs with
      increasing N reflects a loss of temporal fine structure information. Here,
      subjects with moderate hearing loss were tested in a similar experiment. F0DLs
      were measured for tones with three successive harmonics, added in cosine or
      alternating phase. The center frequency was 2000 Hz. N was varied by changing the
      mean F0. A background noise was used to mask combination tones. F0 was roved
      across trials and N was roved by +/-1, to reduce use of excitation pattern cues.
      F0DLs were smaller for cosine than for alternating phase for four out of six
      subjects, and this occurred once N exceeded 5. In contrast to the result for
      normally hearing subjects, F0DLs decreased with increasing N. Performance was
      much worse than obtained for normally hearing subjects at the same center
      frequency, suggesting that most of the hearing-impaired subjects had a poor
      ability to use temporal fine structure information.

PMID- 17030478
TI  - Brazilian plants as possible adaptogens: an ethnopharmacological survey of books
      edited in Brazil.
AB  - In a survey, from Brazilian books, we searched plants that are in popular use for
      purposes resembling those of an adaptogen. This study focused on 24 books by
      authors from diverse regions in the country, resulting in a total of 1317
      citations of uses related to a possible adaptogen effect from approximately 766
      plants. Only species native to Brazil, cited in at least four books, were
      selected, resulting a total of 33 species, belonging to 24 families. Of these,
      four species have been studied previously in relation to effects that are
      considered as part of an adaptogen effect (anti-stress, memory enhancement,
      increased physical and/or sexual performance): Heteropterys aphrodisiaca
      (Malpighiaceae), Paullinia cupana (Sapindaceae), Ptychopetalum olacoides
      (Olacaceae), and Turnera diffusa (Turneraceae). Three others--Pfaffia glomerata,
      Pfaffia paniculata (Amaranthaceae), and Trichilia catigua (Meliaceae)--have also
      been the object of pharmacological studies that support their use as a possible
      adaptogen, but they are listed in less than four books. The overall results
      obtained in the present review of Brazilian folk literature reveals that Brazil
      is rich in plants with potential adaptogen-like effect, but lacks pharmacological
      studies (mostly clinical ones) to confirm these therapeutic properties.

PMID- 17030479
TI  - Stimulative effects of Ulmus davidiana Planch (Ulmaceae) on osteoblastic MC3T3-E1
      cells.
AB  - Ulmus davidiana Planch (Ulmaceae) has long been known to have anti-inflammatory
      and protective effects on damaged tissue, inflammation and bone among other
      functions. To treat rheumatoid arthritis (RA), a herbal medicine, Ulmus davidiana
      Planch (Ulmaceae) extract (UD) is being used in traditional oriental medicine.
      The effect of UD on the proliferation and osteoblastic differentiation in non
      transformed osteoblastic cells (MC3T3-E1) was studied. UD dose-dependently
      increased DNA synthesis (significant at 5-20 microg/ml). UD increased alkaline
      phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (5
      20 microg/ml). Antiestrogen tamoxifen eliminated the stimulation of proliferation
      and ALP activity of MC3T3-E1, which was induced by UD. UD at concentrations
      ranged from 30 to 100 microg/ml inhibited prostaglandin E2 production in MC3T3
      E1. These results indicate that UD directly stimulates cell proliferation and
      differentiation of osteoblasts. These results also suggest and UD is effective
      for bone anti-resorptive action in bone cells.

PMID- 17030480
TI  - Medicinal smokes.
AB  - All through time, humans have used smoke of medicinal plants to cure illness. To
      the best of our knowledge, the ethnopharmacological aspects of natural products'
      smoke for therapy and health care have not been studied. Mono- and multi
      ingredient herbal and non-herbal remedies administered as smoke from 50 countries
      across the 5 continents are reviewed. Most of the 265 plant species of mono
      ingredient remedies studied belong to Asteraceae (10.6%), followed by Solanaceae
      (10.2%), Fabaceae (9.8%) and Apiaceae (5.3%). The most frequent medical
      indications for medicinal smoke are pulmonary (23.5%), neurological (21.8%) and
      dermatological (8.1%). Other uses of smoke are not exactly medical but beneficial
      to health, and include smoke as a preservative or a repellent and the social use
      of smoke. The three main methods for administering smoke are inhalation, which
      accounts for 71.5% of the indications; smoke directed at a specific organ or body
      part, which accounts for 24.5%; ambient smoke (passive smoking), which makes up
      the remaining 4.0%. Whereas inhalation is typically used in the treatment of
      pulmonary and neurological disorders and directed smoke in localized situations,
      such as dermatological and genito-urinary disorders, ambient smoke is not
      directed at the body at all but used as an air purifier. The advantages of smoke
      based remedies are rapid delivery to the brain, more efficient absorption by the
      body and lower costs of production. This review highlights the fact that not
      enough is known about medicinal smoke and that a lot of natural products have
      potential for use as medicine in the smoke form. Furthermore, this review argues
      in favor of medicinal smoke extended use in modern medicine as a form of drug
      delivery and as a promising source of new active natural ingredients.

PMID- 17030481
TI  - Quantitative structure-activity relationship studies of HIV-1 integrase
      inhibition. 1. GETAWAY descriptors.
AB  - The GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) approach has been
      applied to the study of the HIV-1 integrase inhibition of 172 compounds that
      belong to 11 different chemistry families. A model able to describe more than
      68.5% of the variance in the experimental activity was developed with the use of
      the mentioned approach. In contrast, none of the five different approaches,
      including the use of Randic Molecular Profiles, Geometrical, RDF, 3D-MORSE and
      WHIM descriptors was able to explain more than 62.4% of the variance in the
      mentioned property with the same number of variables in the equation. Finally,
      after extracting five compounds considered by us as outliers the model was able
      to describe more than 72.5% of the variance in the experimental activity.

PMID- 17030482
TI  - Structure-based pharmacophore of COX-2 selective inhibitors and identification of
      original lead compounds from 3D database searching method.
AB  - A four-point pharmacophore of COX-2 selective inhibitors was derived from a
      training set of 16 compounds, using the Catalyst program. It consists of a H bond
      acceptor, two hydrophobic groups and an aromatic ring, in accordance with SAR
      data of the compounds and with topology of the COX-2 active site. This
      hypothesis, combined with exclusion volume spheres representing important
      residues of the COX-2 binding site, was used to virtually screen the Maybridge
      database. Eight compounds were selected for an in vitro enzymatic assay. Five of
      them show COX-2 inhibition close to that of nimesulide and rofecoxib, two
      reference COX-2 selective inhibitors. As a result, structure-based pharmacophore
      generation was able to identify original lead compounds, inhibiting the COX-2
      isoform.

PMID- 17030483
TI  - Structural modifications of benzanilide derivatives, effective potassium channel
      openers. X.
AB  - Large-conductance calcium-activated potassium (BK) channels are involved in many
      fundamental cell functions. Consistently, the ability to activate BK channels by
      exogenous compounds is considered as a promising pharmacodynamic pattern for the
      potential treatment of several pathologies. In this perspective, the development
      of new and selective BK-openers can be considered as an actual field of research.
      This paper reports the synthesis and pharmacological evaluation of new
      benzanilides, useful for deepening the comprehension of the structure-activity
      relationships, emerged in previous studies on this class of BK-activators. From a
      structural point of view, these benzanilides belong to a general class of BK
      activators, showing a common pharmacophoric model, consisting of two aryl groups
      linked through an appropriate "spacer" and the almost obligatory presence of a
      phenolic hydroxyl. In particular, a new series of benzanilides, in which the
      phenyl rings have been widely changed both on the acidic portion and the basic
      one of the amide spacer, were synthesised. Their vasorelaxing effects, induced
      through the activation of BK channels, were also evaluated. Although many
      compounds exhibited effects which could not be attributed to the activation of BK
      channels, two derivatives showed a clear profile of BK-activators with
      vasodilator activity comparable to or slightly lower than that recorded for the
      reference benzimidazolone NS1619. A further molecular modelling approach allowed
      us to obtain a molecular electrostatic potential feature which suggests a
      suitable interaction with the receptor site of the BK channel, from a tri
      dimensional point of view. This approach seems to represent a further
      contribution for the development of new BK-activators, designed on the basis of
      the pharmacophoric model above-mentioned.

PMID- 17030484
TI  - Synthesis and biological evaluation of new 4H-pyrano[2,3-b]quinoline derivatives
      that block acetylcholinesterase and cell calcium signals, and cause
      neuroprotection against calcium overload and free radicals.
AB  - The synthesis and biological evaluation of ethyl 5-amino-4-(3-pyridyl)-2-methyl
      6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinoline-3-carboxylates (9-11) is described.
      We have found that these compounds inhibit AChE with a mild potency, mitigates
      the [Ca(2+)](c) triggered by high K(+), and cause neuroprotection against Ca(2+)
      overloading and free radical-induced neuronal death.

PMID- 17030485
TI  - [Medical care for HIV infection in France in 2005, the NADIS cohort study on 7416
      patients].
AB  - OBJECTIVE: This study had for aim to evaluate the immuno-virological and
      therapeutic profile of a cohort of 7416 HIV-1 infected patients followed in six
      French hospital with the Nadis software. METHOD: This cross sectional and
      retrospective study was performed between June 1, 2004 and June 1, 2005. We
      analyzed the demographic (sex, age, HIV infection route), immunovirological, and
      therapeutic characteristics (last treatment prescribed) of the 7416 cohort
      patients. RESULTS: The mean age was 43 years, 29% were women and 29% HCV/HBV co
      infected. The viral load was 1.9 log(10)copies/ml (IQR: 1.5-3.3) and the CD4
      cells count was 452/mm(3) [IQR: 306-630]. Among the 5,913 antiretroviral treated
      patients, VL was less than 200 copies/ml for 74.7% of patients and 50% of them
      had a CD4 cell count superior to 500/mm(3); the drug regimen was 2 or 3
      nucleosides reverse transcriptase inhibitors (NRTI) combined with one protease
      inhibitor (88% Ritonavir boosted) in 42% of the patients, 26% of them were
      treated with 2 NRTI and 1 non-NRTI, and 14% with 3NRTI. Patients with
      undetectable VL were followed 5.1/year versus 7.2 for non- VL controlled patients
      (P<10(-3)). The heterosexual route predominated among the new 531 HIV-diagnosed
      patients among whom 25% had a median CD4 cell count of 242/ m(3). CONCLUSION:
      Close to 75% of antiretroviral treated patients had a VL<200 copies/ml but 15%
      kept a low CD4 cell count. The characteristics of recently diagnosed HIV positive
      patients stresses the need for more information on prevention and an early
      diagnosis.

PMID- 17030486
TI  - Clinical and biological abnormalities in patients after fasciolosis treatment.
AB  - OBJECTIVE: The aim of this communication was to report clinical disorders and
      biological abnormalities in patients followed over a 3- to 18-year period after
      the last date of fasciolosis treatment. These observations were noted in 87
      individuals (out of 711) during a 30-year epidemiological survey. RESULTS: We
      noted diffuse pain in the right hypochondrium, persisting 2 to 6 years after
      treatment (3.7% of persons), and weight loss appearing during treatment and
      persisting afterwards (2.1%). CONCLUSIONS: Our current state of knowledge leads
      us to asking whether pain in the right hypochondrium and weight loss would not be
      due to the presence of persistent hepatic lesions following fasciolosis
      treatment. Other investigations in patients after treated fasciolosis are
      necessary to confirm these abnormalities and determine their frequency.

PMID- 17030487
TI  - [Is liver biopsy still useful?].

PMID- 17030488
TI  - [Pulmonary thrombosis as a complication of Mediterranean spotted fever].
AB  - INTRODUCTION: Thromboembolic complications were uncommon in mediterranean spotted
      fever. OBSERVATION: We report a case of 55-years- old man who was admitted for
      mediterranean spotted fever. Two days later, the patient developed chest pain due
      to a pulmonary thrombosis confirmed by angio-CT. The outcome was good with
      heparin therapy. The investigation for another cause of thrombosis was negative.
      CONCLUSION: Mediterranean spotted fever is usually a moderately severe self
      limited illness. Pulmonary thrombosis was uncommon associated with severe
      disease.

PMID- 17030491
TI  - Experiences of service user and carer participation in health care education.
AB  - The agenda of involving service users and their carers more meaningfully in the
      development, delivery and evaluation of professional education in health is
      gaining in importance. The paper reports on a symposium which presented three
      diverse initiatives, established within a school of nursing and midwifery in the
      United Kingdom. These represent different approaches and attempts to engage
      service users and in some instances carers more fully in professional education
      aimed at developing mental health practitioners. Each is presented as achieving
      movement on a continuum of participation from service users as passive recipients
      to service users as collaborators and co-researchers. The paper concludes with a
      discussion of the lessons to be learnt which will hopefully stimulate service
      user involvement on a wider basis.

PMID- 17030490
TI  - [Is subclinical hypothyroidism a cardiovascular risk factor?].
AB  - OBJECTIVES: Subclinical hypothyroidism defined by the presence of elevated TSH
      levels but normal free T4 level is a common situation. Its consequences on health
      are yet on debate and the interest of a precocious treatment remains surrounded
      by controversy. KEY POINTS: The relationship between subclinical hypothyroidism
      and cardiovascular disease has been evaluated by several cross-sectional and
      longitudinal studies. Subclinical hypothyroidism has direct but subtle effects on
      the heart function, on the peripheral vascular resistance, and is associated with
      a mild elevation of LDL-cholesterol levels; all abnormalities may be partly
      reversed by a thyroxine supplementation. Data of the literature give insufficient
      evidence as to whether subclinical hypothyroidism is an independent
      cardiovascular risk factor. However treatment of subjects with TSH levels up or
      near to 10 mU/l would probably be beneficial in the prevention of cardiovascular
      disease. FUTURE PROSPECTS: Based on observational and interventional studies
      there are some arguments on the benefit of euthyroidism restoration only in
      patients with TSH levels superior to 10 mU/l.

PMID- 17030492
TI  - Attitudes towards disability in an undergraduate nursing curriculum: a literature
      review.
AB  - In the process of introducing a new disability unit into an undergraduate nursing
      curriculum in a New Zealand educational setting, the opportunity arose to conduct
      a small study comparing the attitudes of student nurses towards people with
      disabilities. This paper discusses the literature reviewed, which formed the
      basis for the study. A range of perspectives and research was identified that
      explored societal and nurses' attitudes, disability studies in undergraduate
      nursing curricula, the impact of nurses' attitudes on patient care, and
      interventions for changing those attitudes. Effective nursing care can be
      severely compromised through negative attitudes, and concerns are expressed at
      the lack of attention given to this issue in nursing curricula generally. The
      literature showed that combining educational approaches with opportunities for
      student nurses to interact with disabled people provides the most effective means
      for student nurses to develop positive attitudes towards disabled people. The
      goal for nurse educators is to ensure the inclusion of disability studies as a
      core component in undergraduate nursing education.

PMID- 17030493
TI  - Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage
      among adults and older children in Australian Aboriginal communities.
AB  - Nasopharyngeal carriage of Streptococcus pneumoniae in unimmunised adults and
      older children in three remote Australian Aboriginal communities was compared in
      2002 and 2004. Universal childhood pneumococcal vaccination with a catch-up
      program was introduced in late 2001. Carriage prevalence across all age groups of
      pneumococcal serotypes included in the 7-valent vaccine was 10% in both 2002 and
      2004 (12 and 30 months after introduction of vaccination). This carriage
      prevalence was lower than anticipated. It is likely that indirect effects of
      childhood vaccination occurred before the 2002 survey. To further assess indirect
      effects on carriage of childhood pneumococcal vaccination, data prior to 2002 are
      required. Between 12 and 30 months following introduction of conjugate
      pneumococcal vaccination, indirect effects on carriage were unchanged.

PMID- 17030494
TI  - Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and
      viral pathogens in the upper respiratory tract.
AB  - Otitis media (OM) is a major burden for all children, particularly for Australian
      Aboriginal children. Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus
      influenzae and viruses (including rhinovirus and adenovirus) are associated with
      OM. We investigated nasopharyngeal microbial interactions in 435 samples
      collected from 79 Aboriginal and 570 samples from 88 non-Aboriginal children in
      Western Australia. We describe a multivariate random effects model appropriate
      for analysis of longitudinal data, which enables the identification of two
      independent levels of correlation between pairs of pathogens. At the microbe
      level, rhinovirus infection was positively correlated with carriage of S.
      pneumoniae, H. influenzae and M. catarrhalis, and adenovirus with M. catarrhalis.
      Generally, there were positive associations between bacterial pathogens at both
      the host and microbe level. Positive viral-bacterial associations at the microbe
      level support previous findings indicating that viral infection can predispose an
      individual to bacterial carriage. Viral vaccines may assist in reducing the
      burden of bacterial disease.

PMID- 17030495
TI  - Population dynamics of Bordetella pertussis in Finland and Sweden, neighbouring
      countries with different vaccination histories.
AB  - Pertussis is an infectious disease of the respiratory tract in humans caused by
      Bordetella pertussis. Despite extensive vaccinations, pertussis has remained
      endemic and re-emerged. In Finland, a whole-cell pertussis vaccine has been used
      since 1952 with high coverage. In Sweden, whole-cell vaccinations were introduced
      in 1953 but ceased in 1979, and pertussis vaccinations with acellular vaccines
      were introduced in 1996. Two epidemic peaks occurred in Sweden in 1999 and 2002
      and in Finland in 1999 and 2003. We compared Finnish (N=193) and Swedish (N=455)
      B. pertussis isolates circulating in 1998-2003 together with vaccine strains used
      in these neighbouring countries with different vaccination histories. The
      isolates were analysed by serotyping, genotyping of pertussis toxin S1 subunit
      and pertactin, and pulsed-field gel electrophoresis. The results suggest that the
      sequential epidemics were caused by clonal expansion of a certain B. pertussis
      strain possibly transmitted from Sweden to Finland. The roles of antigenic
      variation in immunity-driven evolution of B. pertussis in both countries are
      discussed.

PMID- 17030496
TI  - Contrasting roles for reactive oxygen species and nitric oxide in the innate
      response to pulmonary infection with Streptococcus pneumoniae.
AB  - The pulmonary innate response to low-dose bacterial challenge requires
      functioning alveolar macrophages (AM) but also subsequent macrophage apoptosis.
      To address the role of reactive oxygen species (ROS) and nitric oxide (NO) in AM
      apoptosis, sub-clinical Streptococcus pneumoniae infection was established in
      gp91(phox-/-) and inducible NO synthase deficient (iNOS(-/-)) mice. Both AM
      apoptosis and the number of macrophages containing apoptotic bodies are reduced
      in iNOS(-/-) as compared to control or gp91(phox-/-) mice. iNOS(-/-) mice recruit
      neutrophils and generate TNF-alpha to compensate for impaired AM competence but
      ROS deficiency has no apparent effect on AM function in this model.

PMID- 17030497
TI  - An overview of acute otitis media in Australian Aboriginal children living in
      remote communities.
AB  - Australian Aboriginal children experience early, persistent and severe middle ear
      infections. We conducted a review of the medical literature that addressed acute
      otitis media (AOM) in Australian Aboriginal children. Comparisons were made with
      the recent guidelines on the diagnosis and management of AOM prepared by the
      American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis
      media in Aboriginal children living in remote communities begins in the first 3
      months of life following early bacterial colonisation. Young children with
      persistent signs of suppurative disease (bulging of the tympanic membrane or
      middle ear discharge) are probably most at risk of developing chronic suppurative
      otitis media.

PMID- 17030498
TI  - Reassortment between human A(H3N2) viruses is an important evolutionary
      mechanism.
AB  - Phylogenetic relationships of whole genomes of H3N2 viruses circulating in
      Germany during a 6-year period from 1998 to 2005 revealed the co-circulation of
      different lineages of viruses. Multiple reassortment events occurred during this
      time between viruses belonging to different lineages or different subgroups.
      Strains isolated during 1998-1999 were characterised by a surprisingly high
      heterogeneity and multiple reassortment events. Seventy percent of the examined
      1998-1999 viruses had completely different genome compositions. To our knowledge,
      such an exceptional high proportion of different reassortant strains,
      encompassing all eight genome segments, have not been described before. In
      contrast, only one reassortant virus was prevalent during 1999-2000 even though
      two of the three 1998-1999 lineages were co-circulating. Reassortant viruses were
      isolated also in each of the other seasons. However, the proportion of H3N2
      viruses with different genome compositions varied from season to season. Strains
      with a reassortant NA played an important role and were also detected during 2003
      2004 and 2004-2005 accounting for 45% and 70% of the circulating H3N2 viruses,
      respectively. Moreover, different reassortment events occurring during these
      seasons included also the PB1, PB2 and NP genes. The results presented here
      emphasize that genetic reassortment is an important factor in the evolution of
      H3N2 viruses and highlight the need for a comprehensive analysis of influenza
      viruses, especially with regard to the annual vaccine composition.

PMID- 17030499
TI  - A comparison of the Alcohol Use Disorder Identification Test (AUDIT) in general
      population surveys in nine European countries.
AB  - AIMS: This study explored the suitability of the Alcohol Use Disorder
      Identification Test (AUDIT) for cross-national comparable estimates of problem
      drinking in general populations. On the item level the focus is on responsiveness
      to cross-national and gender differences. For the set of items the focus is on
      intercorrelations between items, indicating to what extent the AUDIT constitutes
      a scale. METHODS: General population surveys from nine European countries were
      included. Cross-tabulations were used to analyse cross-national and gender
      differences in scores on the items. Reliability analysis was used to analyse
      intercorrelations between the items. RESULTS: The items 'blackouts' (men and
      women) and 'guilt and remorse' (women) are the most frequently reported
      consequences. Gender differences tended to be smaller for 'guilt and remorse' and
      'concern of others', and largest for 'morning drinking'. The reliability analysis
      shows that in eight of the nine countries frequency of drinking lowers the alpha.
      Injury and concern of others lead to a lower internal consistency in three
      countries. CONCLUSIONS: There was sufficient variation between countries in the
      pattern of responses and variation in gender differences to conclude that the set
      of consequence items was responsive to national and gender differences in problem
      drinking. Frequency of drinking was not a good indicator of problem drinking. The
      country differences in item total correlations of consequences might be due to
      differences in how these items are interpreted. Decisions on which items to
      include in an instrument to allow comparison of estimates of problem drinking
      cross-nationally require studies on how these items are interpreted in general
      populations of different countries.

PMID- 17030500
TI  - Social inequalities in alcohol consumption and alcohol-related problems in the
      study countries of the EU concerted action 'Gender, Culture and Alcohol Problems:
      a Multi-national Study'.
AB  - AIMS: We investigated the presence of social inequalities of alcohol use and
      misuse using educational attainment as an indicator of socio-economic status in
      15 countries: Sweden, Norway, Finland, Germany, The Netherlands, Switzerland,
      Hungary, the Czech Republic, Israel, Brazil, and Mexico. METHODS: Study surveys
      were independently conducted and the data centrally analysed. Most samples were
      national. Survey modes and sample sizes varied. The age range was restricted to
      between 25 and 59 years of age. Socio-economic status was measured by educational
      level. Multiple logistic regressions were employed to calculate age-adjusted odds
      ratios for men and women in each country by educational level for current
      drinking status, heavy drinking (>or=20 g ethanol per day for women, >or=30 g a
      day for men), heavy episodic (binge) drinking, and alcohol-related problems
      (using AUDIT). RESULTS: Men and women demonstrated similar patterns in
      inequalities with regard to current drinking status within a country. In Germany,
      The Netherlands, France, Switzerland, and Austria higher educated women were most
      likely to drink heavily, while among men the lower educated were more at risk in
      most countries. For heavy episodic drinking, almost no significant differences
      were evident among women, but for men a social gradient was observable with lower
      educated being more at risk in several countries. Among five countries with data
      from the AUDIT, men of lower education in Finland, Czech Republic, and Hungary
      had higher risks to report problems. Nordic countries shared a common pattern in
      social inequalities as did two Latin American countries, while a mixed picture
      was observed for middle European countries. Social inequalities in the two Latin
      American countries display a pattern emerging in other research on developing
      countries: namely that those in the higher educated groups are more likely to
      consume alcohol in a risky manner. CONCLUSIONS: Patterns in the distribution of
      social inequalities are not universal. Social inequalities in alcohol use differ
      by gender according to alcohol measure used and differ also across groups of
      countries. These variations should be taken into account when formulating
      international and cross-cultural alcohol policies.

PMID- 17030501
TI  - Introduction to special issue 'Gender, Culture and Alcohol Problems: a Multi
      national Study'.
AB  - This paper provides an introduction to a series of articles reporting results
      from the EU concerted action "Gender, Culture and Alcohol Problems: A Multi
      national Study" which examined differences in drinking among women and men in 13
      European and two non-European countries. The gender gap in alcohol drinking is
      one of the few universal gender differences in human social behavior. However,
      the size of these differences varies greatly from one society to another. The
      papers in this issue examine, across countries, (1) men's and women's drinking
      patterns, (2) the prevalence of men's and women's experience of alcohol-related
      problems, (3) gender differences in social inequalities in alcohol use and abuse,
      (4) gender differences in the influence of combinations of social roles on heavy
      alcohol use, and (5) how societal-level factors predict women's and men's alcohol
      use and problems on a regional and global level. Country surveys were
      independently conducted and then centralized at one institution for further data
      standardization and processing. Several results indicated that the greater the
      societal gender equality in a country, the smaller the gender differences in
      drinking behavior. In most analyses the smallest gender differences in drinking
      behaviour were found in Nordic countries, followed by western and central
      European countries, with the largest gender differences in countries with
      developing economies.

PMID- 17030502
TI  - Gender and cultural differences in the association between family roles, social
      stratification, and alcohol use: a European cross-cultural analysis.
AB  - AIMS: First, this paper investigates (i) gender differences in associations of
      social stratification, family roles, and heavy drinking, and (ii) country
      differences in these associations. Second, it seeks to explain country
      differences in the associations of social stratification and family roles with
      alcohol consumption by societal level variables. METHODS: Survey data of 25 to 49
      years-old from eight European countries were used. Logistic regressions were used
      to analyse gender differences in the association between family roles (marriage,
      having children), social stratification (education, employment), and heavy
      drinking (>20 g/day for women; 30 g/day for men). Gender differences were tested
      by means of interactions between gender and social stratification/family roles.
      Structural measures of work desirability, social welfare, and gender equity were
      used to explain differences in associations across countries. RESULTS: The
      associations between social stratification, family roles, and heavy drinking
      varied across gender and countries. A country's social welfare system was
      associated with heavy drinking only among women. Women in countries with a strong
      social welfare system, such as Nordic countries, tended to drink more heavily if
      employed, having lower formal education, and a non-traditional family role. In
      countries with weak social welfare systems or work desirability, heavy drinking
      was associated with high education, while effects of family roles and employment
      were small. CONCLUSIONS: It appeared that the social welfare system and gender
      equity of a country determines to a large extent how education, employment, and
      family roles are associated with heavy drinking.

PMID- 17030503
TI  - The influence of societal level factors on men's and women's alcohol consumption
      and alcohol problems.
AB  - AIMS: To identify the pattern of gender differences in drinking across societies,
      and to its association with other societal characteristics. METHODS: The
      aggregated results of GENACIS project surveys in 29 countries were examined and
      were compared with other characteristics of these societies. RESULTS: In all the
      participating societies men's drinking was more prevalent and heavier than
      women's drinking. Differences between countries in the gender gap in drinking
      were strongly associated with women's position in society, as well as with
      modernization. Similar results were obtained for indicators of alcohol's adverse
      consequences. CONCLUSIONS: Gender differences should be studied not only as
      individual behaviours, but also as societal traits, associated with other
      characteristics of the social system.

PMID- 17030504
TI  - Drinking patterns and their gender differences in Europe.
AB  - AIMS: To compare drinking habits and to examine differences between drinking
      cultures in different regions and countries in Europe; to examine gender
      differences in drinking habits and to compare them over countries. METHODS: Data
      consisted of independently conducted, centrally analysed surveys in the general
      population aged 20-64 years in 14 European countries. Central measures were
      abstention, frequency and volume of drinking overall and by beverage type,
      amounts drunk per drinking day, and heavy episodic drinking. RESULTS: There were
      clear gender differences in all drinking measures, except for wine drinking.
      Differences between genders were often smaller than average in northern Europe.
      Gender ratios did not show systematic changes by age, with the exception that
      young men and women differed less than older men and women in the frequency of
      heavy episodic drinking. The results on beverage preferences indicate that the
      distinction among wine/beer/spirits cultures have implicitly been based on male
      drinking. Our expectation was for more daily light drinking integrated in
      everyday life in the Mediterranean countries, more heavy episodic drinking
      associated with weekends and celebrations in the North, with the traditional beer
      countries somewhere in between. The differences observed were usually in the
      direction expected. However, no country represented an ideal type of drinking
      culture, i.e. drinking for 'mood-changing effects' only or for 'nutritional
      purposes' only; all countries were mixtures of these two extremes. CONCLUSIONS:
      There were clear and consistent gender differences in all countries, while the
      differences in drinking between countries and regions were not as obvious.

PMID- 17030505
TI  - PbGCbeta is essential for Plasmodium ookinete motility to invade midgut cell and
      for successful completion of parasite life cycle in mosquitoes.
AB  - When malaria parasites enter to mosquitoes, they fertilize and differentiate to
      zygotes and ookinetes. The motile ookinetes cross the midgut cells and arrive to
      the basement membranes where they differentiate into oocysts. The midgut
      epithelium is thus a barrier for ookinetes to complete their life cycle in the
      mosquitoes. The ookinetes develop gliding motility to invade midgut cells
      successfully, but the molecular mechanisms behind are poorly understood. Here, we
      identified a single molecule with guanylate cyclase domain and N-terminal P-type
      ATPase like domain in the rodent malaria parasite Plasmodium berghei and named it
      PbGCbeta. We demonstrated that transgenic parasites in which the PbGCbeta gene
      was disrupted formed normal ookinetes but failed to produce oocyst. Confocal
      microscopic analysis showed that the disruptant ookinetes remained on the surface
      of the microvilli. The disruptant ookinetes showed severe defect in motility,
      resulting in failure of parasite invasion of the midgut epithelium. When the
      disruptant ookinetes were cultured in vitro, they transformed into oocysts and
      sporozoites. These results demonstrate that PbGCbeta is essential for ookinete
      motility when passing through the midgut cells, but not for further development
      of the parasites.

PMID- 17030506
TI  - Involvement of p38 MAP kinase in not only activation of the phagocyte NADPH
      oxidase induced by formyl-methionyl-leucyl-phenylalanine but also determination
      of the extent of the activity.
AB  - Activated NADPH oxidase in neutrophils produces superoxide. We investigated the
      role of p38 MAP kinase in activating NADPH oxidase stimulated by the bacteria
      derived peptide fMLP. fMLP-stimulated superoxide production was completely
      abolished by SB203580, a p38 MAP kinase inhibitor, whereas anisomycin, a p38 MAP
      kinase activator, did not induce superoxide production, indicating that p38 MAP
      kinase was essential, but not sufficient, for NADPH oxidase activation.
      Anisomycin pretreatment strongly activated p38 MAP kinase in fMLP-stimulated
      cells, accompanied by greatly increased superoxide production, suggesting that
      p38 MAP kinase determines the extent of the fMLP-stimulated NADPH oxidase
      activity. Furthermore, superoxide production was remarkably reactivated by
      cytochalasin B addition after fMLP-stimulated production had disappeared, and
      this was correlated with highly activated p38 MAP kinase. These results suggest
      that p38 MAP kinase is involved not only in activating NADPH oxidase stimulated
      by fMLP but also in determining the extent of its activity.

PMID- 17030507
TI  - Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates
      atherosclerosis progression accelerated by bacterial exposure.
AB  - Epidemiological studies suggest the association of periodontal infections with
      atherosclerosis, however, the mechanism underlying this association remains
      poorly understood. Porphyromonas gingivalis is the primary etiologic agent of
      adult periodontitis and produces a unique class of cysteine proteinases
      consisting of Arg-gingipain (Rgp) and Lys-gingipain (Kgp). To elucidate key
      mechanisms for progression of atherosclerosis by P. gingivalis infection, we
      tested the effects of the disruption of genes encoding Rgp and/or Kgp and
      inhibitors specific for the respective enzymes on atherosclerosis progression in
      apolipoprotein E-knockout mice. Repeated intravenous injection of wild-type P.
      gingivalis resulted in an increase in atherosclerotic lesions as well as an
      increase in the serum LDL cholesterol and a decrease of HDL cholesterol in these
      animals. LDL particles in P. gingivalis-injected animals were modified as a
      result of selective proteolysis of apoB-100 in LDL particles. This modification
      of LDL by P. gingivalis resulted in an increase in LDL uptake by macrophages and
      consequent foam cell formation in vitro. The atherosclerotic changes induced by
      P. gingivalis infection were attenuated by disruption of Rgp-encoding genes or by
      an Rgp-specific inhibitor. Our results indicate that degradation of apoB-100 by
      Rgp plays a crucial role in the promotion of atherosclerosis by P. gingivalis
      infection.

PMID- 17030508
TI  - An RNA aptamer that discriminates bovine factor IX from human factor IX.
AB  - An RNA aptamer has been selected by SELEX against bovine factor IX using an RNA
      pool containing 74-nucleotides randomized region. Selected RNA aptamer (Clone 5)
      could discriminate bovine factor IX effectively from human factor IX.
      Interestingly, the nucleotide regions 73-78 and 80-83 of the selected aptamer
      were determined to be important for bovine factor IX-binding using phosphate
      interference. Based on phosphate interference and binding studies the minimal
      motif for aptamer with discriminating ability is found with the nucleotide
      regions from 65 to 106. The discriminating ability of this mini aptamer is
      calculated as more than 1,000 fold. The equilibrium dissociation constant (K(d))
      for the above complex was 10 nM as determined by surface plasmon resonance. Based
      on the available structural informations, probable binding site of aptamer on the
      target was predicted.

PMID- 17030509
TI  - Phosphatidylinositol 3-kinase-dependent modulation of carnitine
      palmitoyltransferase 1A expression regulates lipid metabolism during
      hematopoietic cell growth.
AB  - An abundant supply of extracellular nutrients is believed to be sufficient to
      suppress catabolism of cellular macromolecules. Here we show that, despite
      abundant extracellular nutrients, interleukin-3-deprived hematopoietic cells
      begin to catabolize intracellular lipids. Constitutive Akt activation blunts the
      increased beta-oxidation that accompanies growth factor withdrawal, and in growth
      factor-replete cells, phosphatidylinositol 3-kinase (PI3K) signaling is required
      to suppress lipid catabolism. Surprisingly, PI3K and Akt exert these effects by
      suppressing expression of the beta-oxidation enzyme carnitine
      palmitoyltransferase 1A (CPT1A). Cells expressing a short hairpin RNA against
      CPT1A fail to induce beta-oxidation in response to growth factor withdrawal and
      are unable to survive glucose deprivation. When CPT1A is constitutively
      expressed, growth factor stimulation fails to repress beta-oxidation. As a
      result, both net lipid synthesis and cell proliferation are diminished. Together,
      these results demonstrate that modulation of CPT1A expression by PI3K-dependent
      signaling is the major mechanism by which cells suppress beta-oxidation during
      anabolic growth.

PMID- 17030510
TI  - Protein kinase C-induced activation of a ceramide/protein phosphatase 1 pathway
      leading to dephosphorylation of p38 MAPK.
AB  - Recently we showed that, in human breast cancer cells, activation of protein
      kinase C by 4beta-phorbol 12-myristate 13-acetate (PMA) produced ceramide formed
      from the salvage pathway (Becker, K. P., Kitatani, K., Idkowiak-Baldys, J.,
      Bielawski, J., and Hannun, Y. A. (2005) J. Biol. Chem. 280, 2606-2612). In this
      study, we investigated intracellular signaling events mediated by this novel
      activated pathway of ceramide generation. PMA treatment resulted in transient
      activation of mitogen-activated protein kinases (ERK1/2, JNK1/2, and p38)
      followed by dephosphorylation/inactivation. Interestingly, fumonisin B1 (FB1), an
      inhibitor of the salvage pathway, attenuated loss of phosphorylation of p38,
      suggesting a role for ceramide in p38 dephosphorylation. This was confirmed by
      knock-down of longevity-assurance homologue 5, which partially suppressed the
      formation of C(16)-ceramide induced by PMA and increased the phosphorylation of
      p38. These results demonstrate a role for the salvage pathway in feedback
      inhibition of p38. To determine which protein phosphatases act in this pathway,
      specific knock-down of serine/threonine protein phosphatases was performed, and
      it was observed that knock-down of protein phosphatase 1 (PP1) catalytic subunits
      significantly increased p38 phosphorylation, suggesting activation of PP1 results
      in an inhibitory effect on p38. Moreover, PMA recruited PP1 catalytic subunits to
      mitochondria, and this was significantly suppressed by FB1. In addition, phospho
      p38 resided in PMA-stimulated mitochondria. Upon PMA treatment, a mitochondria
      enriched/purified fraction exhibited significant increases in C(16)-ceramide, a
      major ceramide specie, which was suppressed by FB1. Taken together, these data
      suggest that accumulation of C(16)-ceramide in mitochondria formed from the
      protein kinase C-dependent salvage pathway results at least in part from the
      action of longevity-assurance homologue 5, and the generated ceramide modulates
      the p38 cascade via PP1.

PMID- 17030511
TI  - Swt1, a novel yeast protein, functions in transcription.
AB  - The conserved TREX complex couples transcription to nuclear mRNA export. Here, we
      report that the uncharacterized open reading frame YOR166c genetically interacts
      with TREX complex components and encodes a novel protein named Swt1 for
      "synthetically lethal with TREX." Co-immunoprecipitation experiments show that
      Swt1 also interacts with the TREX complex biochemically. Consistent with a
      potential role in transcription as suggested by its interaction with TREX, Swt1
      localizes mainly to the nucleus. Importantly, deletion of Swt1 leads to decreased
      transcription. Taken together, these data suggest that Swt1 functions in gene
      expression in conjunction with the TREX complex.

PMID- 17030512
TI  - Dynamics of myosin heavy chain gene regulation in slow skeletal muscle: role of
      natural antisense RNA.
AB  - The evolutionarily conserved order of the skeletal muscle myosin heavy chain
      (MHC) genes and their close tandem proximity on the same chromosome are
      intriguing and may be important for their coordinated regulation. We investigated
      type II MHC gene regulation in slow-type muscle fibers undergoing a slow to fast
      MHC transformation in response to inactivity, 7 days after spinal cord isolation
      (SI) in rats. We examined the transcriptional products of both the sense and
      antisense strands across the IIa-IIx-IIb MHC gene locus. A strand-specific
      reverse transcription (RT)-PCR approach was utilized to study the expression of
      the mRNA, the primary transcript (pre-mRNA), the antisense RNA overlapping the
      MHC genes, and both the intergenic sense and antisense RNAs. Results showed that
      the mRNA and pre-mRNA of each MHC had a similar response to SI, suggesting
      regulation of these genes at the transcriptional level. In addition, we detected
      previously unknown antisense strand transcription that produced natural antisense
      transcripts (NATs). RT-PCR mapping of the RNA products revealed that the
      antisense activity resulted in the formation of three major products: aII, xII,
      and bII NATs (antisense products of the IIa, IIx, and IIb genes, respectively).
      The aII NAT begins in the IIa-IIx intergenic region in close proximity to the IIx
      promoter, extends across the 27-kb IIa MHC gene, and continues to the IIa MHC
      gene promoter. The expression of the aII NAT was significantly up-regulated in
      muscles after SI, was negatively correlated with IIa MHC gene expression, and was
      positively correlated with IIx MHC gene expression. The exact role of the aII NAT
      is not clear; however, it is consistent with the inhibition of IIa MHC gene
      transcription. In conclusion, NATs may mediate cross-talk between adjacent genes,
      which may be essential to the coordinated regulation of the skeletal muscle MHC
      genes during dynamic phenotype shifts.

PMID- 17030513
TI  - S100A16, a novel calcium-binding protein of the EF-hand superfamily.
AB  - S100A16 protein is a new and unique member of the EF-hand Ca(2+)-binding
      proteins. S100 proteins are cell- and tissue-specific and are involved in many
      intra- and extracellular processes through interacting with specific target
      proteins. In the central nervous system S100 proteins are implicated in cell
      proliferation, differentiation, migration, and apoptosis as well as in cognition.
      S100 proteins became of major interest because of their close association with
      brain pathologies, for example depression or Alzheimer's disease. Here we report
      for the first time the purification and biochemical characterization of human and
      mouse recombinant S100A16 proteins. Flow dialysis revealed that both homodimeric
      S100A16 proteins bind two Ca(2+) ions with the C-terminal EF-hand of each
      subunit, the human protein exhibiting a 2-fold higher affinity. Trp fluorescence
      variations indicate conformational changes in the orthologous proteins upon
      Ca(2+) binding, whereas formation of a hydrophobic patch, implicated in target
      protein recognition, only occurs in the human S100A16 protein. In situ
      hybridization analysis and immunohistochemistry revealed a widespread
      distribution in the mouse brain. Furthermore, S100A16 expression was found to be
      astrocyte-specific. Finally, we investigated S100A16 intracellular localization
      in human glioblastoma cells. The protein was found to accumulate within nucleoli
      and to translocate to the cytoplasm in response to Ca(2+) stimulation.

PMID- 17030514
TI  - CKAP4/p63 is a receptor for the frizzled-8 protein-related antiproliferative
      factor from interstitial cystitis patients.
AB  - Antiproliferative factor (APF) is a low molecular weight sialoglycopeptide that
      is secreted by bladder cells from interstitial cystitis patients and is a potent
      inhibitor of both normal bladder epithelial and bladder carcinoma cell
      proliferation. We hypothesized that APF may produce its antiproliferative effects
      by binding to a transmembrane receptor. This study demonstrates that cytoskeleton
      associated protein 4/p63 (CKAP4/p63), a type II transmembrane receptor, binds
      with high affinity to APF. The antiproliferative activity of APF is effectively
      inhibited by preincubation with anti-CKAP4/p63-specific antibodies, as well as by
      short interfering RNA knockdown of CKAP4/p63. Immunofluorescent confocal
      microscopy showed co-localization of anti-CKAP4/p63 and rhodamine-labeled
      synthetic APF binding in both cell membrane and perinuclear areas. APF also
      inhibits the proliferation of HeLa cervical carcinoma cells that are known to
      express CKAP4/p63. These data indicate that CKAP4/p63 is an important epithelial
      cell receptor for APF.

PMID- 17030515
TI  - Efficacy of daptomycin in the treatment of experimental endocarditis due to
      susceptible and multidrug-resistant enterococci.
AB  - OBJECTIVES: Daptomycin was tested in vitro and in rats with experimental
      endocarditis against the ampicillin-susceptible and vancomycin-susceptible
      Enterococcus faecalis JH2-2, the vancomycin-resistant (VanA type) mutant of
      strain JH2-2 (strain JH2-2/pIP819), and the ampicillin-resistant and vancomycin
      resistant (VanB type) Enterococcus faecium D366. METHODS: Rats with catheter
      induced aortic vegetations were treated with doses simulating intravenously
      kinetics in humans of daptomycin (6 mg/kg every 24 h), amoxicillin (2 g every 6
      h), vancomycin (1 g every 12 h) or teicoplanin (12 mg/kg every 12 h). Treatment
      was started 16 h post-inoculation and continued for 2 days. RESULTS: MICs of
      daptomycin were 1, 1 and 2 mg/L, respectively, for strains JH2-2, JH2-2/pIP819
      and D366. In time-kill studies, daptomycin showed rapid (within 2 h) bactericidal
      activity against all strains. Daptomycin was highly bound to rat serum proteins
      (89%). In the presence of 50% rat serum, simulating free concentrations,
      daptomycin killing was maintained but delayed (6-24 h). In vivo, daptomycin
      treatment resulted in 10 of 12 (83%), 9 of 11 (82%) and 11 of 12 (91%) culture
      negative vegetations in rats infected with strains JH2-2, JH2-2/pIP819 and D366,
      respectively (P < 0.001 compared to controls). Daptomycin efficacy was comparable
      to that of amoxicillin and vancomycin for susceptible isolates. Daptomycin,
      however, was significantly (P < 0.05) more effective than teicoplanin against the
      glycopeptide-susceptible strain JH2-2 and superior to all comparators against
      resistant isolates. CONCLUSIONS: These results support the use of the newly
      proposed daptomycin dose of 6 mg/kg every 24 h for treatment of enterococcal
      infections in humans.

PMID- 17030516
TI  - Expression of the las and rhl quorum-sensing systems in clinical isolates of
      Pseudomonas aeruginosa does not correlate with efflux pump expression or
      antimicrobial resistance.
AB  - OBJECTIVES: Quorum-sensing systems regulate expression of several virulence
      factors and may affect the MexAB-OprM efflux system in Pseudomonas aeruginosa.
      This study investigated the relationship between two quorum-sensing systems,
      efflux pump MexAB-OprM expression and antimicrobial resistance in 33 clinical
      isolates of P. aeruginosa. METHODS: Expression of the quorum-sensing regulatory
      genes lasR and rhlR was assessed by real time RT-PCR. The autoinducer synthetase
      genes lasI and rhlI and the regulatory genes mexT and mexS were characterized by
      DNA sequencing. Production of pyocyanin and elastase in each of the isolates was
      also determined. RESULTS: While there was a significant correlation between
      expression of the quorum-sensing regulatory genes and production of pyocyanin and
      elastase, there was no correlation with expression of mexA or with antimicrobial
      resistance. There were no mutations in lasI, rhlI, mexT or mexS that correlated
      with quorum-sensing expression. CONCLUSIONS: Increased activity of two quorum
      sensing systems in P. aeruginosa does not contribute to increased mexA expression
      or antimicrobial resistance.

PMID- 17030517
TI  - spa typing of methicillin-resistant Staphylococcus aureus isolated from domestic
      animals and veterinary staff in the UK and Ireland.
AB  - OBJECTIVES: Region X of the protein A gene (spa) was sequenced from methicillin
      resistant Staphylococcus aureus (MRSA) isolates originating from animals, humans
      and the environment at veterinary hospitals in the UK and Ireland. MRSA
      transmission between animals and veterinary staff was assessed on the basis of
      spa typing, PFGE and epidemiological data. METHODS: MRSA isolates from dogs (n =
      27), horses (n = 9), cats (n = 6), staff (n = 22) and environmental surfaces (n =
      3) were analysed by PFGE and spa typing. Known contacts between human and animal
      MRSA carriers were ascertained from the veterinary hospitals. RESULTS: All
      feline, most canine (96%) and human (82%) isolates showed PFGE profiles that were
      either indistinguishable (subtype A1) or closely related (subtypes A2-A10) to
      that of the epidemic clone EMRSA-15 (CC22), whereas most equine isolates (88%)
      were related to CC8 (types C, D, E and G). spa polymorphism enabled
      discrimination among MRSA strains assigned to the same PFGE type. Fifteen spa
      types clustering into two distinct groups were detected, with t032 being the most
      prevalent (48%). The spa and PFGE types of MRSA isolated from seven staff members
      were the same as those of strains isolated from infected animals attended by the
      staff. CONCLUSIONS: Irrespective of geographical origin, MRSA isolated from
      equine and small animal hospitals generally clustered into two distinct clonal
      complexes, CC8 and CC22, respectively. The combined use of spa and PFGE typing
      allowed better discrimination than each method used individually, and provided
      useful information on MRSA transmission between animal and human individuals.

PMID- 17030518
TI  - Impact of the Hospital Pharmacy Initiative for promoting prudent use of
      antibiotics in hospitals in England.
AB  - OBJECTIVES: In July 2003, the UK Department of Health announced an allocation of
      12 million pounds sterling to hospital pharmacists to improve the monitoring and
      control of anti-infective use over the ensuing 3 year period (the Hospital
      Pharmacy Initiative, or HPI). Chief Pharmacists were asked to use this money for
      developments to promote prudent antibiotic use and monitoring of antimicrobials
      within their Trusts. This study aimed to evaluate the impact of the HPI funding,
      which at the time had been in place for nearly 2 years, on pharmacy activities in
      this area. METHODS: A postal questionnaire was sent to the pharmacy department of
      each acute hospital Trust in England, aiming to provide a descriptive overview of
      the activities of hospital pharmacy staff in the field of anti-infectives and to
      explore the extent to which these activities were made possible by the HPI
      funding. RESULTS: One hundred and forty-one specialist antimicrobial pharmacy
      staff were employed in 130 responding Trusts; 89% were pharmacists, 7% pharmacy
      technicians and the remainder administrative staff. Three-quarters of these staff
      had been employed due to the funding, resulting in review of antimicrobial
      prescribing guidelines, antibiotic audit projects and multidisciplinary work with
      Microbiology/Infectious Diseases staff. Thirteen Trusts gave details of drug
      acquisition cost savings; over the course of a year, these Trusts saved 1.1
      million pounds sterling in total. CONCLUSIONS: The HPI funding has facilitated
      greater interaction between Pharmacy and Microbiology/Infectious Diseases
      departments than was previously possible. Significant reductions in antibiotic
      acquisition costs have been demonstrated, though further work is warranted to
      fully establish the impact of pharmacy activities on clinical and microbiological
      outcomes.

PMID- 17030519
TI  - Tigecycline does not induce proliferation or cytotoxin production by epidemic
      Clostridium difficile strains in a human gut model.
AB  - OBJECTIVES: Data on the risk of Clostridium difficile infection (CDI) associated
      with specific antibiotics are difficult to obtain because of confounding clinical
      factors. It is particularly important to evaluate the propensity of new
      antibiotics to induce CDI. We have examined the propensity of tigecycline to
      induce CDI using a human gut model. METHODS: We used a three-stage chemostat
      human gut model to study the effects of tigecycline on indigenous gut microflora
      and C. difficile. Two epidemic C. difficile were studied in separate experiments:
      PCR ribotype 001 (UK, CD001) and PCR ribotype 027 (North America, CD027).
      Tigecycline MICs for 39 C. difficile representing 19 distinct PCR ribotypes were
      also determined. RESULTS: Tigecycline MICs were 0.06 mg/L for all the C.
      difficile strains. Peak tigecycline concentrations in the gut model were 10.9 and
      11.7 mg/L in CD027 and CD001 experiments, respectively. Tigecycline instillation
      invoked marked decreases in numbers of bacteroides and bifidobacteria (10(7)
      10(8) cfu/mL) and lesser reductions in facultative anaerobes. Despite markedly
      altered gut microflora, CD001 and CD027 remained as spores for the duration of
      the experiment, with no evidence of proliferation or cytotoxin production.
      CONCLUSIONS: Tigecycline exposure did not induce C. difficile proliferation or
      cytotoxin production despite reduced competing microflora. The potency of
      tigecycline against C. difficile may contribute to the low risk of CDI induction.
      Factors other than gut microflora colonization resistance may be important in
      preventing C. difficile spore germination, proliferation and cytotoxin
      production.

PMID- 17030520
TI  - Coronary flow reserve in dilated cardiomyopathy: an important pathophysiological
      tool to be considered among, but not instead of, other well-established
      prognostic factors.

PMID- 17030521
TI  - Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients
      undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial
      Infarction: the randomized multicentre CASTEMI study.
AB  - AIMS: To examine the safety and efficacy of intravenous caldaret in patients with
      large acute ST-elevation myocardial infarction (STEMI) undergoing percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: STEMI patients (n=387) with >
      or =10 mm summed ST-deviation on electrocardiogram were randomized to receive a
      48 h infusion of caldaret 57.5 mg [lower dose (LD)], caldaret 172.5 mg [higher
      dose (HD)], or placebo, starting before PCI. Both HD and LD were well tolerated.
      In 247 patients with pre-PCI TIMI 0/1, there was no effect of HD or LD on single
      photon emission computed tomography infarct size or ejection fraction assessed at
      Day 7 and Day 30. Subgroup analyses suggest that future work in patients with
      anterior MI might be warranted. CONCLUSION: This first human experience with
      caldaret prior to direct PCI for large STEMI shows a good safety profile. No
      evidence of efficacy was discerned. Subgroup analyses in anterior MI patients
      showed some effects in endpoints studied, however, these findings require
      confirmation in a further study if a drug effect is to be established.

PMID- 17030522
TI  - Subclinical atherosclerosis of lower limb arteries: a strong predictor for
      cardiovascular mortality.

PMID- 17030523
TI  - Outcome of implantable cardioverter defibrillators in adults with congenital
      heart disease: a multi-centre study.
AB  - AIMS: To investigate outcome and complications of implantable cardioverter
      defibrillators (ICDs) in adults with congenital heart disease (CHD) and to
      identify predictors of (in-) appropriate shocks. METHODS AND RESULTS: Sixty-four
      CHD patients >/= 18 years at first ICD implantation [63% tetralogy of Fallot
      (TOF) and age at implantation 37 +/- 13 years] were identified using the Dutch
      adult CHD registry and a Belgian tertiary care centre database. Median follow-up
      duration was 3.7 years. Early complications included pocket haematoma (n = 3),
      lead failure (n = 2), and pneumothorax (n = 2). Late complications occurred in 11
      (17%) patients, including lead failure (n = 6) and and electrical storm (n = 3).
      Overall, 30 device-related re-interventions were performed in 20 patients (31%),
      including four premature generator changes and seven lead replacements. Half of
      the patients received one or more shocks, and 46 shocks in 15 patients (23%) were
      classified as appropriate. One hundred and sixty shocks in 26 patients (41%) were
      classified as inappropriate. No predictors of (in-)appropriate shocks were
      identified, except TOF being associated with less appropriate shocks than
      patients with other CHD (HR 0.29, P = 0.02). CONCLUSION: The ICD provided
      effective therapy in a quarter of adults with CHD with low complication rates.
      The incidence of inappropriate shocks, however, appeared to be excessive and
      warrants further attention.

PMID- 17030524
TI  - Prognostic role of combination of coronary flow reserve with aortic
      distensibility indices.

PMID- 17030525
TI  - Factors associated with HIV sero-positivity in young, rural South African men.
AB  - OBJECTIVE: To describe factors associated with HIV infection in men aged 15-26
      years. SETTING: Rural Eastern Cape Province, South Africa. SAMPLE: A total of
      1277 sexually experienced Xhosa male volunteers from 70 villages participating in
      a cluster randomized controlled trial of an HIV behavioural intervention. Xhosas
      circumcise during manhood initiation rituals. DESIGN: Cross-sectional, analysis
      of the study's baseline interviews. MAIN MEASURE: HIV sero-status, sexual
      practices measured with an interviewer-administered questionnaire. RESULTS: About
      2% of the men were HIV positive. A logistic regression model showed HIV
      positivity to be associated with age (OR 1.55; 95%CI 1.22-1.95), having made a
      woman pregnant (OR 2.93; 95% CI 1.28-6.68), having been circumcised (OR 0.40; 95%
      CI 0.16-0.98), and having had sex with a man (OR 3.61; 95% CI 1.0-13.0).
      CONCLUSIONS: Our findings provide further evidence to suggest that circumcision
      is protective. There was much heterosexual risk taking among men but only
      pregnancy (with its association with sexual frequency) predicted HIV sero
      positivity. Although relatively rare, same-sex sexual experiences were a risk
      factor. Male-male sexual contact is rarely assessed in HIV research in Africa and
      almost never addressed in general HIV prevention programming. Our findings
      suggest that it should be given more attention.

PMID- 17030526
TI  - Child routines and youths' adherence to treatment for type 1 diabetes.
AB  - OBJECTIVE: Type 1 diabetes (T1DM) is a chronic life-threatening disease that
      requires strict adherence to daily treatment tasks. Although necessary for
      survival, children who present with behavior problems tend to show problems
      complying with the treatment regimen, thereby increasing their risk for morbidity
      and premature mortality. The risk of poor treatment adherence is hypothesized to
      be lower for these children, however, if they engage in more routine behaviors.
      Given the potential clinical implications, this hypothesis and two theoretical
      models proposed to elucidate the underlying psychological process for the role of
      child routines in treatment adherence were evaluated empirically. The first model
      hypothesized that child routines protect (moderator variable) behaviorally
      problematic children from poor treatment adherence, whereas the alternative model
      hypothesized that child routines mediate the relation between childhood behavior
      problems and poor treatment adherence. METHODS: Parents of T1DM patients (N =
      111) ranging from 6 to 16 years of age (M = 12 years) reported on their child's
      behavior problems, routine behaviors, and adherence to treatment for T1DM using
      standardized measures. Baron and Kenny's statistical procedures for testing
      moderation and mediation hypotheses were used to evaluate the proposed models.
      RESULTS: Regression analyses did not support the moderation hypothesis but did
      support the hypothesis that engaging in child routines mediates the relation
      between childhood behavior problems and poor treatment adherence. CONCLUSIONS:
      Parents of behaviorally problematic children diagnosed with T1DM might be advised
      to instill routines in their child's daily activities to increase the likelihood
      of treatment adherence, and thereby reduce the risk of morbidity and early
      mortality. Implications for clinical interventions are discussed.

PMID- 17030528
TI  - Escalating polypharmacy.
AB  - New drug treatments, new indications for older drug treatments, lower thresholds
      for treating risk factors in preventative medicine, and an ageing population
      acquiring multiple pathologies all contribute to the development of polypharmacy.
      Longitudinal studies document the rise in prescribed medications, particularly in
      the elderly. The potential dangers of adverse drug reactions and interactions,
      poor adherence and confusion associated with ever-increasing polypharmacy are
      likely to worsen. Strategies to reduce prescribing will obviously decrease the
      dangers of polypharmacy. These include more considered prescribing when
      contemplating additions to patients' already lengthy prescription lists, and
      external reviews of medicine lists by a doctor or pharmacist. Despite such
      strategies, polypharmacy seems inevitable and considerations must be given to
      simplifying patients' multiple drug administrations using single-daily-dose
      regimens, fixed-dose combination pills, calendar-blister packaging and pill
      organizers.

PMID- 17030527
TI  - Risk stratification for in-hospital mortality in spontaneous intracerebral
      haemorrhage: a Classification and Regression Tree analysis.
AB  - BACKGROUND: Risk stratification for mortality in intracerebral haemorrhage (ICH)
      helps guide care, but existing clinical prediction rules are too cumbersome for
      clinical practice because of their complexity. AIM: To develop a simple decision
      tree model of in-hospital mortality risk stratification for ICH patients.
      METHODS: We collected information on spontaneous ICH patients hospitalized in a
      teaching hospital in Japan from August, 1998 to December, 2001 (n = 374). All
      variables were abstracted from data available at the time of initial evaluation.
      A prediction rule for in-hospital mortality was developed by the Classification
      and Regression Tree (CART) methodology. The accuracy of the model was evaluated
      using the area under receiver-operator characteristic curve. RESULTS: Overall in
      hospital mortality rate was 20.2%. The CART methodology identified four groups
      for mortality risk, varying from low (2.1%) to high (58.9%). Level of
      consciousness (coma) was the best single predictor for mortality, followed by
      high ICH volume (cut-off 10.4 ml), and then age (cut-off 75 years). The accuracy
      of our CART model (0.86) exceeded that of a multivariate logistic regression
      model (0.81). DISCUSSION: ICH patients can easily be stratified for mortality
      risk, based on three predictors available on admission. This simple decision tree
      model provides clinicians with a reliable and practical tool.

PMID- 17030529
TI  - A simple score for assessing stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is usually assessed
      using FEV(1) to establish the diagnosis and the severity of the disease. However,
      COPD is now considered a systemic disease. AIM: To evaluate the utility of the
      Health-Activity-Dyspnoea-Obstruction (HADO) score for classifying the severity of
      COPD and predicting outcomes. DESIGN: Prospective longitudinal clinical study.
      METHODS: We studied 611 consecutive patients with stable COPD in five out-patient
      clinics of a teaching hospital. We measured dyspnoea degree, pulmonary function
      (by spirometry), self-reported level of daily physical activity and overall
      health condition. Outcome measures included health-related quality of life
      (HRQoL) parameters (as measured by the generic SF-36 Health Survey and by two
      specific questionnaires, the St George Respiratory Questionnaire and the Chronic
      Respiratory Questionnaire) and mortality at 3 years follow-up. RESULTS: Based on
      the HADO score, COPD was classified as mild in 26.7% of patients, moderate in
      53.3%, and severe in 20%. There were statistically significant correlations
      between these three levels of severity and HRQoL parameters and vital status.
      After adjustment for relevant covariates, the HADO score reliably predicted
      survival and vital status. DISCUSSION: The HADO score can be easily obtained in
      an out-patient clinic, and distinguishes groups of COPD patients by their disease
      severity. The HADO score is better than FEV(1%) alone for predicting mortality at
      3 years.

PMID- 17030531
TI  - Report of a case of congenital malaria Plasmodium malariae in France.
AB  - Congenital malaria (CM) has been considered to be rare, even in malaria-endemic
      areas but the disease can result in significant neonatal morbidity. Because of
      its rarity, the disease may go undiagnosed for a prolonged period in a seriously
      ill infant. We report the first case of Plasmodium malariae CM from a HIV mother.
      HIV could have facilitated the transfer of erythrocytic persistent P. malariae
      through the placenta to the fetus.

PMID- 17030532
TI  - Randomized controlled trial of 7-Day vs. 14-Day antibiotics for neonatal sepsis.
AB  - There are no evidence-based guidelines available regarding the duration of
      antibiotics in neonatal septicemia. We compared the effectiveness of a 7-day
      intravenous antibiotic regimen with the standard 14-day regime in blood-culture
      proven sepsis in neonates. This was a controlled, blinded, randomized trial with
      stratification (for birth weight). Blood-culture-positive septic babies > or =32
      weeks and/or > or =1500 g were enrolled if meningitis and other deep-seated focal
      infections were ruled out. Parental consent was obtained. Randomization to either
      7-day or 14-day therapy was done on day 7 of antibiotics if the baby had
      clinically remitted by day 5. Blood culture was repeated 24 h after antibiotic
      completion. Subjects were observed in the hospital for at least 72 h, and
      followed-up for 28 days by weekly visits and telephonic contacts. The primary
      outcome was treatment failure within 28 days defined as a positive blood culture,
      or clinical signs accompanied by either positive CRP or adjudicated to be a
      relapse by an expert committee. A total of 120 babies were eligible, 51 were
      excluded (no consent: 12; non-remission: 39), and 69 were randomized to receive
      either a 7-day course (n = 34) or a 14-day course (n = 35) of antibiotics.
      Baselines variables were comparable in the two groups. Primary outcome assessment
      could be done in 33 cases in either group. There was a trend to greater treatment
      failures in the 7-day group compared with 14-day group (5 vs. 1, respectively; P
      = 0.19). On subgroup analysis of subjects with Staphylococcus aureus infection,
      those who received 7-day therapy (n = 7) had significantly more treatment failure
      than 14-day therapy (n = 7) (four and zero, respectively; P = 0.022), whereas on
      sub-group analysis of babies with non-S. aureus infections, treatment failure
      rates were identical (3.8% in both groups). On comparing the organisms isolated
      in the group of subjects which was not randomized by virtue of being symptomatic
      (n = 39) vs. the group which was randomized (n = 69), it was found that S. aureus
      infections were significantly commoner in the former group (61.5 vs. 21.3%,
      respectively; P < 0.001). Neonates > or =32 weeks and/or > or =1500 g with S.
      aureus sepsis require 14 days of antibiotics. S. aureus infection is also
      associated with failure to achieve clinical remission by the 5th day of
      antibiotic therapy. Larger trials are required to confirm whether neonates with
      non-S. aureus sepsis, whose symptoms remit by 5 days, can be treated with 7 days
      of antibiotics.

PMID- 17030533
TI  - Could nutritional rehabilitation at home complement or replace centre-based
      therapeutic feeding programmes for severe malnutrition?
AB  - To measure the success rate of three different strategies used in Medecins Sans
      Frontieres large-scale therapeutic nutritional rehabilitation programme in Niger,
      we analysed three cohorts of severely malnourished patients in terms of daily
      weight gain, length of stay, recovery, case fatality and defaulting. A total of
      1937 children aged 6-59 months were followed prospectively from 15 August 2002 to
      21 October 2003. For the three cohorts, 660 children were maintained in the
      therapeutic feeding centre (TFC) during the entire treatment, 937 children were
      initially treated at the TFC and completed treatment at home and 340 children
      were exclusively treated at home. For all cohorts, average time in the programme
      and average weight gain met the international standards (30-40 days, >8
      g/kg/day). Default rates were 28.1, 16.8 and 5.6% for TFC only, TFC plus home
      based and home-based alone strategies, respectively. The overall case fatality
      rate for the entire programme was 6.8%. Case fatality rates were 18.9% for TFC
      only and 1.7% for home-based alone. No deaths were recorded in children
      transferred to rehabilitation at home. This study suggests that satisfactory
      results for the treatment of severe malnutrition can be achieved using a
      combination of home and hospital-based strategies.

PMID- 17030534
TI  - Novel splicing mutation in the progranulin gene causing familial corticobasal
      syndrome.
AB  - Corticobasal syndrome (CBS) is a rare cognitive and movement disorder
      characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical
      sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the
      clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently
      been shown to segregate with truncating mutations in progranulin (PGRN), a
      multifunctional growth factor thought to promote neuronal survival. This study
      identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that
      segregates with CBS in a Canadian family of Chinese origin. We confirmed the
      absence of the mutant PGRN allele in the RT-PCR product which supports the model
      of haploinsufficiency for PGRN-linked disease. This report of mutation in the
      PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in
      FTLD spectrum disorders.

PMID- 17030536
TI  - The quest for florigen: a review of recent progress.
AB  - The photoperiodic induction of flowering is a systemic process requiring
      translocation of a floral stimulus from the leaves to the shoot apical meristem.
      In response to this stimulus, the apical meristem stops producing leaves to
      initiate floral development; this switch in morphogenesis involves a change in
      the identity of the primordia initiated and in phyllotaxis. The physiological
      study of the floral transition has led to the identification of several putative
      floral signals such as sucrose, cytokinins, gibberellins, and reduced N-compounds
      that are translocated in the phloem sap from leaves to the shoot apical meristem.
      On the other hand, the genetic approach developed more recently in Arabidopsis
      thaliana allowed the discovery of many genes that control flowering time. These
      genes function in 'cascades' within four promotive pathways, the 'photoperiodic',
      'autonomous', 'vernalization', and 'gibberellin' pathways, which all converge on
      the 'integrator' genes SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and FLOWERING
      LOCUS T (FT). Recently, several studies have highlighted a role for a product of
      FT as a component of the floral stimulus or 'florigen'. These recent advances and
      the proposed mode of action of FT are discussed here.

PMID- 17030535
TI  - Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation
      in progranulin: a clinicopathologic study.
AB  - We previously reported a kindred with three cases of dementia, in which the
      proband exhibited features typical of frontotemporal dementia and parkinsonism
      (FTDP). An arginine insertion at codon 352 (insR352) in the presenilin-1 (PSEN1)
      gene was identified in the proband, but analyses in plasma and CSF suggested a
      mechanism of neurodegeneration not directly related to amyloid pathophysiology.
      The proband was followed with yearly evaluations of functional, clinical,
      neuropsychologic, neuropsychiatric and radiologic status, which showed relatively
      linear change over the initial 4 years of assessment. Upon the proband's death at
      age 63, neuropathologic examination revealed frontotemporal lobar degeneration
      (FTLD) with ubiquitin-positive inclusions (FTLD-U). We recently identified
      several kindreds with familial FTDP associated with mutations in the progranulin
      (PGRN) gene, particularly in those cases with neuronal intranuclear inclusions.
      Our proband was indeed found to have such inclusions, and PGRN analysis in this
      proband revealed the G to A mutation in the exon 1 splice donor site (IVS1+1G-
      >A) which is predicted to destroy the 5'-splice site of exon 1 and remove the
      start methionine codon and hence completely block any PGRN protein from being
      generated. These findings suggest that the insR352 PSEN1 is not pathogenic, and
      the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and
      represents a new class of neurodegenerative disease--the
      'hypoprogranulinopathies'.

PMID- 17030537
TI  - Respiratory carbon metabolism in the high mountain plant species Ranunculus
      glacialis.
AB  - Very little is known about the primary carbon metabolism of the high mountain
      plant Ranunculus glacialis. It is a species with C3 photosynthesis, but with
      exceptionally high malate content in its leaves, the biological significance of
      which remains unclear. 13C/12C-isotope ratio mass spectrometry (IRMS) and 13C
      nuclear magnetic resonance (NMR) labelling were used to study the carbon
      metabolism of R. glacialis, paying special attention to respiration. Although
      leaf dark respiration was high, the temperature response had a Q10 of 2, and the
      respiratory quotient (CO2 produced divided by O2 consumed) was nearly 1,
      indicating that the respiratory pool is comprised of carbohydrates. Malate, which
      may be a large carbon substrate, was not respired. However, when CO2 fixed by
      photosynthesis was labelled, little labelling of the CO2 subsequently respired in
      the dark was detected, indicating that: (i) most of the carbon recently
      assimilated during photosynthesis is not respired in the dark; and (ii) the
      carbon used for respiration originates from (unlabelled) reserves. This is the
      first demonstration of such a low metabolic coupling of assimilated and respired
      carbon in leaves. The biological significance of the uncoupling between
      assimilation and respiration is discussed.

PMID- 17030538
TI  - Compartmentation in plant metabolism.
AB  - Cell fractionation and immunohistochemical studies in the last 40 years have
      revealed the extensive compartmentation of plant metabolism. In recent years, new
      protein mass spectrometry and fluorescent-protein tagging technologies have
      accelerated the flow of information, especially for Arabidopsis thaliana, but the
      intracellular locations of the majority of proteins in the plant proteome are
      still not known. Prediction programs that search for targeting information within
      protein sequences can be applied to whole proteomes, but predictions from
      different programs often do not agree with each other or, indeed, with
      experimentally determined results. The compartmentation of most pathways of
      primary metabolism is generally covered in plant physiology textbooks, so the
      focus here is mainly on newly discovered metabolic pathways in plants or pathways
      that have recently been revised. Ultimately, all of the pathways of plant
      metabolism are interconnected, and a major challenge facing plant biochemists is
      to understand the regulation and control of metabolic networks. One of the best
      characterized networks links sucrose synthesis in the cytosol with photosynthetic
      CO(2) fixation and starch synthesis in the chloroplasts. One of the key features
      of this network is how the transport of pathway intermediates and signal
      metabolites across the chloroplast envelope conveys information between the two
      compartments, influencing the regulation of several enzymes to co-ordinate fluxes
      through the different pathways. It is widely accepted that chloroplasts and
      mitochondria originated from prokaryotic endosymbionts, and that new transporters
      and regulatory networks evolved to integrate metabolism in these organelles with
      the rest of the cell. Curiously, the present-day locations of many metabolic
      pathways within the cell often do not reflect their evolutionary origin, and
      there is evidence of extensive shuffling of enzymes and whole pathways between
      compartments during the evolution of plants.

PMID- 17030539
TI  - Developmental regulation of a VEIDase caspase-like proteolytic activity in barley
      caryopsis.
AB  - Caspases are essential in animal programmed cell death both as initiator and
      executioner proteases. Plants do not have close caspase homologues, but several
      instances of caspase-like proteolytic activity have been demonstrated in
      connection with programmed cell death in plants. It was asked if caspase-like
      proteases are involved during development of the barley caryopsis. The presence
      of a caspase-6-like proteolytic activity that preferentially cleaved the sequence
      VEID was demonstrated. A range of protease inhibitors was tested and only caspase
      specific inhibitors showed major inhibitory effects. The profile of VEIDase
      activity in developing starchy endosperm, embryo, and whole caryopsis was
      measured and showed a general trend of higher activity in young, rapidly
      developing tissues. The VEIDase activity was localized in vivo to vesicles, shown
      to be autophagosomes, in randomly distributed cells of the starchy endosperm. The
      VEIDase activity detected in barley caryopsis is similar to activities described
      previously in mammals, spruce, yeast, and thale cress. In mammals, spruce, and
      yeast, VEIDase activity has been shown to be positively correlated with the
      occurrence of programmed cell death. Several manifestations of programmed cell
      death exist in developing barley caryopsis, indicating a connection between
      VEIDase activity and developmental programmed cell death in barley.

PMID- 17030540
TI  - 3D lidar imaging for detecting and understanding plant responses and canopy
      structure.
AB  - Understanding and diagnosing plant responses to stress will benefit greatly from
      three-dimensional (3D) measurement and analysis of plant properties because plant
      responses are strongly related to their 3D structures. Light detection and
      ranging (lidar) has recently emerged as a powerful tool for direct 3D measurement
      of plant structure. Here the use of 3D lidar imaging to estimate plant properties
      such as canopy height, canopy structure, carbon stock, and species is
      demonstrated, and plant growth and shape responses are assessed by reviewing the
      development of lidar systems and their applications from the leaf level to canopy
      remote sensing. In addition, the recent creation of accurate 3D lidar images
      combined with natural colour, chlorophyll fluorescence, photochemical reflectance
      index, and leaf temperature images is demonstrated, thereby providing information
      on responses of pigments, photosynthesis, transpiration, stomatal opening, and
      shape to environmental stresses; these data can be integrated with 3D images of
      the plants using computer graphics techniques. Future lidar applications that
      provide more accurate dynamic estimation of various plant properties should
      improve our understanding of plant responses to stress and of interactions
      between plants and their environment. Moreover, combining 3D lidar with other
      passive and active imaging techniques will potentially improve the accuracy of
      airborne and satellite remote sensing, and make it possible to analyse 3D
      information on ecophysiological responses and levels of various substances in
      agricultural and ecological applications and in observations of the global
      biosphere.

PMID- 17030541
TI  - Horizontal gene transfer in plants.
AB  - Horizontal gene transfer (HGT) has played a major role in bacterial evolution and
      is fairly common in certain unicellular eukaryotes. However, the prevalence and
      importance of HGT in the evolution of multicellular eukaryotes remain unclear.
      Recent studies indicate that plant mitochondrial genomes are unusually active in
      HGT relative to all other organellar and nuclear genomes of multicellular
      eukaryotes. Although little about the mechanisms of plant HGT is known, several
      studies have implicated parasitic plants as both donors and recipients of
      mitochondrial genes. Most cases uncovered thus far have involved a single
      transferred gene per species; however, recent work has uncovered a case of
      massive HGT in Amborella trichopoda involving acquisition of at least a few dozen
      and probably hundreds of foreign mitochondrial genes. These foreign genes came
      from multiple donors, primarily eudicots and mosses. This review will examine the
      implications of such massive transfer, the potential mechanisms and consequences
      of plant-to-plant mitochondrial HGT in general, as well as the limited evidence
      for HGT in plant chloroplast and nuclear genomes.

PMID- 17030542
TI  - ABP1 expression regulated by IAA and ABA is associated with the cambium
      periodicity in Eucommia ulmoides Oliv.
AB  - A cDNA clone of Eucommia ulmoides Oliv. encoding auxin binding protein 1 (ABP1),
      one of the putative receptors of auxin, was isolated, and the seasonal expression
      of ABP1 in relation to IAA and ABA annual variation was investigated by different
      technical approaches including RT-PCR, real-time PCR, northern blotting, western
      blotting, and immunolocalization. In the cambial region, ABP1 expression at both
      the protein and the mRNA level was found to be high, low, and remarkably scarce
      in the active, quiescent, and resting stages, respectively, during cambium
      periodicity. The signal abundance of ABP1 follows the opposite pattern to ABA
      accumulation and correlates with auxin responsiveness of the cambial tissues,
      suggesting a role for ABP1 in mediating auxin-dependent regulation of cambial
      activation in the activity-dormancy cycle. This paper attempts to explain why IAA
      would 'boost' the reactivation of a quiescent cambium, and not that of a resting
      cambium. Results also show that ABP1 expression is improved by IAA, while
      inhibited by ABA.

PMID- 17030543
TI  - Clinical benefit of fulvestrant in postmenopausal women with advanced breast
      cancer and primary or acquired resistance to aromatase inhibitors: final results
      of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability
      of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with
      hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment.
      PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative
      study. Two patient groups were prospectively considered: group A (n=70) with AI
      responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250
      mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All
      patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67%
      had bone metastases and 45% liver metastases. Fulvestrant administration was well
      tolerated and yielded a clinical benefit (CB; defined as objective response or
      stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to
      39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B.
      Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A
      and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of
      patients who had progressed following prior AI treatment gained CB with
      fulvestrant, thereby delaying indication to start chemotherapy. Prior response to
      an AI did not appear to be predictive for benefit with fulvestrant.

PMID- 17030544
TI  - Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth
      factor with multiple biological activities in preventing chemotherapy- and
      radiotherapy-induced mucositis.
AB  - Oral and intestinal mucositis are among the most significant dose-limiting toxic
      effects of intensive cancer treatment and are associated with adverse clinical
      and economic outcomes. Palifermin (Kepivancetrade mark), an N-truncated
      recombinant human keratinocyte growth factor-1, is the first agent to be approved
      for prevention of oral mucositis. Keratinocyte growth factor, a potent epithelial
      mitogen, appears to play a major role in the healing process. Palifermin has
      multiple biological activities that appear to protect the mucosal epithelium and
      promote its early regeneration after irradiation- and chemotherapy-induced
      injury. These include inhibition of epithelial cell apoptosis and DNA damage, up
      regulation of detoxifying enzymes and down-regulation of pro-inflammatory
      cytokines, as well as enhanced migration, proliferation and differentiation of
      epithelial cells. Palifermin reduces the incidence, severity and duration of oral
      mucositis in patients with haematological malignancies undergoing myelotoxic
      conditioning therapy and haematopoietic stem-cell transplantation. Clinical
      sequelae, including febrile neutropenia and resource use (opioid analgesia and
      parenteral feeding), are concomitantly reduced. Other potential applications
      being explored include use in the solid tumour setting, reduction of intestinal
      mucositis and reduction of GVHD in allogenic transplantation. Thus, the
      development of palifermin and other potential new agents for preventing
      chemotherapy- and radiotherapy-induced mucositis represents an important
      breakthrough in oncological supportive care.

PMID- 17030545
TI  - Late risk of relapse and mortality among postmenopausal women with estrogen
      responsive early breast cancer after 5 years of tamoxifen.
AB  - BACKGROUND: Letrozole after 5 years of adjuvant tamoxifen results in a
      significant reduction in risk of recurrence from estrogen receptor (ER) positive
      breast cancer. An individualized estimate of the risk of relapse and death after
      5 years of tamoxifen could improve decisions regarding extended hormonal therapy.
      METHODS: The British Columbia Breast Cancer Outcomes database was used to
      identify women aged 45 years or older at the time of diagnosis with early-stage
      (I-IIIA) breast cancer who received tamoxifen and were disease free 5 years after
      diagnosis. Ten-year breast cancer event rates and mortality were calculated as
      well as annualized hazard rates of recurrence. RESULTS: A total of 1086 women
      were identified with a median age of 64 years and follow-up of 10.5 years. The
      relative risk (RR) of death was 3.1 (P=0.003) and for recurrence was 1.7
      (P=0.037) for N1 (one to three positive nodes) versus N0 (zero nodes positive)
      disease. N2 (four to nine nodes positive) had a RR of 5.8 (P<0.001) for death and
      3.0 (P=0.002) for recurrence. Low tumor grade and high ER level subgroups had a
      more favorable prognosis. Annual breast cancer risk between years 6 and 10 was,
      respectively, 2.2%, 3.5% and 7.6% for N0, N1 and N2 disease and 2.6% and 4.5% for
      T1 and T2 breast cancer. CONCLUSION: T and N stages predicted late relapse and
      death from breast cancer in a population-based cohort of postmenopausal women.
      Risk estimates reported herein may be used to optimize decision making regarding
      adjuvant therapy after 5 years of tamoxifen.

PMID- 17030546
TI  - Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive
      patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter
      phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
AB  - BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil
      (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse
      effect profiles. This trial assessed efficacy and safety of the triple
      combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally
      advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND
      METHODS: A total of 43 eligible patients were treated with intravenous infusions
      of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2
      h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS:
      Among all 43 patients, the tumor response rate was 19% [95% confidence interval
      7% to 30%]. Nine patients were nonassessable for response because they did not
      complete the first two cycles of chemotherapy due to rapid disease progression,
      early death or treatment refusal. One patient was lost to follow-up. Median time
      to progression and overall survival were 5.7 and 7.5 months. Principal grade
      III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%),
      nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of
      patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION:
      Response rates and survival of the three-drug combination compare favorably with
      single-agent gemcitabine, but do not exceed results for doublets.

PMID- 17030547
TI  - Epidemiology of peritoneal mesothelioma: a review.
AB  - The epidemiology of peritoneal mesothelioma is complicated by possible geographic
      and temporal variations in diagnostic practices. The incidence rates in
      industrialized countries range between 0.5 and three cases per million in men and
      between 0.2 and two cases per million in women. Exposure to asbestos is the main
      known cause of peritoneal mesothelioma. Results on peritoneal mesothelioma have
      been reported for 34 cohorts exposed to asbestos, among which a strong
      correlation was present between the percentages of deaths from pleural and
      peritoneal mesothelioma (correlation coefficient 0.8, P < 0.0001). Studies of
      workers exposed only or predominantly to chrysotile asbestos resulted in a lower
      proportion of total deaths from peritoneal mesothelioma than studies of workers
      exposed to amphibole or mixed type of asbestos. Cases of peritoneal mesothelioma
      have also been reported following exposure to erionite and Thorotrast, providing
      further evidence of common etiological factors with the pleural form of the
      disease. The role of other suspected risk factors, such as simian virus 40
      infection and genetic predisposition, is unclear at present. Control of asbestos
      exposure remains the main approach to prevent peritoneal mesothelioma.

PMID- 17030548
TI  - Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2)
      with celecoxib in metastatic colorectal cancer: a GERCOR study.
AB  - BACKGROUND: Oxaliplatin stop and go in combination with leucovorin and 5
      fluorouracil has been successfully used in a previous study (OPTIMOX1) in
      metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug
      with anti-neoplastic properties. In the present study, celecoxib was evaluated in
      combination with FOLFOX7 regimen and as a single agent in maintenance therapy.
      PATIENTS AND METHODS: This phase II study examined for previously untreated MCR
      patients the stop-and-go procedure [six cycles of folinic acid, 5FU and
      oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and
      reintroduction at progression] with continuous administration of celecoxib (800
      mg/day). RESULTS: Forty-four patients were included, 42 eligible: performance
      status (%) 0/1/2=45/40/15, median age 60 (31-76) years. Response rate (RR) was
      43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median
      overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity
      9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and
      vomiting 2.4%. Median CFI 1 (n=27) duration was 3.9 months (range 2-39 months).
      CONCLUSION: With an acceptable safety profile, celecoxib combined with FOLFOX7
      achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These
      results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6
      months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2
      in maintenance therapy.

PMID- 17030549
TI  - MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in
      patients with bone metastases--preliminary clinical experience.
AB  - BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a
      noninvasive thermal ablation technique, shown to be clinically effective in the
      treatment of uterine fibroids and is being evaluated as a method of thermal
      ablation of benign and malignant breast tumors. To evaluate the safety and
      initial efficacy of MRgFUS for the palliation of pain caused by bone metastases,
      in patients for whom other treatments are either not effective or not feasible.
      MATERIALS AND METHODS: Thirteen patients suffering from symptomatic bone
      metastases underwent MRgFUS procedure. Treatment safety was evaluated by
      assessing the incidence and severity of device-related complications up to 6
      months after treatment. Effectiveness of pain palliation was evaluated by visual
      analog scale, pain questionnaires and changes in the patients' medication.
      RESULTS: Fifteen procedures were carried out. Mean follow-up was 59 days. Twelve
      patients received adequate treatment and were available for follow-up. Two
      patients died due to disease progression during the first month after treatment.
      No severe adverse events were recorded. The remaining 10 patients reported
      prolonged improvement in pain score and/or reduced analgesic dosage. CONCLUSION:
      MRgFUS may provide a safe and effective noninvasive alternative for the
      palliation of pain, caused by bone metastases.

PMID- 17030550
TI  - Health-related quality of life in disease-free survivors of breast cancer with
      the general population.
AB  - BACKGROUND: Although most of the literature about health-related quality of life
      (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in
      disease-free breast cancer survivors with that of the general population.
      MATERIALS AND METHODS: We administered the European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life
      Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck
      Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors
      for over 1 year after being diagnosed with stage 0 to III breast cancer. We
      performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The
      scores for some health-related quality of life [corrected] HRQoL scales were
      comparable for both disease-free breast cancer survivors and the general female
      population, but [corrected] there was a [corrected] clinically significant
      difference between the two groups [corrected] in cognitive and social
      functioning, fatigue, insomnia, financial difficulties, body image, future
      perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease
      free survivors of breast cancer had good HRQoL, which was less affected by the
      type of treatment than it was by demographic characteristics, time since surgery,
      comorbidity, fatigue, and depression.

PMID- 17030551
TI  - Constructing socio-economic status indices: how to use principal components
      analysis.
AB  - Theoretically, measures of household wealth can be reflected by income,
      consumption or expenditure information. However, the collection of accurate
      income and consumption data requires extensive resources for household surveys.
      Given the increasingly routine application of principal components analysis (PCA)
      using asset data in creating socio-economic status (SES) indices, we review how
      PCA-based indices are constructed, how they can be used, and their validity and
      limitations. Specifically, issues related to choice of variables, data
      preparation and problems such as data clustering are addressed. Interpretation of
      results and methods of classifying households into SES groups are also discussed.
      PCA has been validated as a method to describe SES differentiation within a
      population. Issues related to the underlying data will affect PCA and this should
      be considered when generating and interpreting results.

PMID- 17030552
TI  - Who suffers from indoor air pollution? Evidence from Bangladesh.
AB  - In this paper, we investigate individuals' exposure to indoor air pollution.
      Using new survey data from Bangladesh, average hours spent by members of
      households in the cooking area, living area and outdoors in a typical day are
      combined with the estimates of pollution concentration in different locations in
      order to estimate exposure. We analyse exposure at two levels: differences within
      households attributable to family roles, and differences across households
      attributable to income and education. Within households, we relate individuals'
      exposure to pollution in different locations during their daily round of
      activities. We find high levels of exposure for children and adolescents of both
      sexes, with particularly serious exposure for children under 5 years. Among prime
      age adults, we find that men have half the exposure of women (whose exposure is
      similar to that of children and adolescents). We also find that elderly men have
      significantly lower exposure than elderly women. Across households, we draw on
      results from a previous paper, which relate pollution variation across households
      to choices of cooking fuel, cooking locations, construction materials and
      ventilation practices. We find that these choices are significantly affected by
      family income and adult education levels (particularly for women). Overall, we
      find that the poorest, least-educated households have twice the pollution levels
      of relatively high-income households with highly educated adults. Our findings
      further suggest that young children and poorly educated women in poor households
      face pollution exposures that are four times those for men in higher income
      households organized by more highly educated women. Since infants and young
      children suffer the worst mortality and morbidity from indoor air pollution, in
      this paper we consider measures for reducing their exposure. Our recommendations
      for reducing the exposure of infants and young children are based on a few
      simple, robust findings. Hourly pollution levels in cooking and living areas are
      quite similar because cooking smoke diffuses rapidly and nearly completely into
      living areas. However, outdoor pollution is far lower. At present, young children
      are only outside for an average of 3 hours per day. For children in a typical
      household, pollution exposure can be halved by adopting two simple measures:
      increasing their outdoor time from 3 to 5 or 6 hours per day, and concentrating
      outdoor time during peak cooking periods.

PMID- 17030553
TI  - Phytolith assemblages and systematic associations in grassland species of the
      South-eastern Pampean plains, Argentina.
AB  - BACKGROUND AND AIMS: Phytolith descriptions of South American plant species are
      scarce. This knowledge is crucial for the interpretation of the fossil phytolith
      record of a region. In this study phytolith assemblages and systematic
      relationships of the main grasses and Asteraceae species of Paspalum quadrifarium
      grassland are described. METHODS: Phytoliths from leaves of Poaceae and
      Asteraceae species were extracted by using a calcination technique. For each
      species, 350-400 phytoliths were counted and the relative frequency of each
      morphotype was calculated. Phytolith assemblages were subject to principal
      components analysis (PCA) and cluster analysis (Morisita index). KEY RESULTS: PCA
      and cluster analysis showed family (Poaceae vs. Asteraceae) and subfamily (within
      Poaceae) differentiation. Exceptions to general trends described for other
      species were detected. Floristic variants of Paspalum quadrifarium grassland can
      be separated by their phytolith assemblages. CONCLUSIONS: The study provides a
      reference collection of phytolith assemblages of the main Poaceae and Asteraceae
      species of Paspalum quadrifarium grassland and describes some phytolith
      morphotypes/systematic relationships useful for the analysis of fossil phytolith
      assemblages of the Pampean region.

PMID- 17030554
TI  - Haplotypes spanning SPEC2, PDZ-GEF2 and ACSL6 genes are associated with
      schizophrenia.
AB  - Chromosome 5q22-33 is a region where studies have repeatedly found evidence for
      linkage to schizophrenia. In this report, we took a stepwise approach to
      systematically map this region in the Irish Study of High Density Schizophrenia
      Families (ISHDSF, 267 families, 1337 subjects) sample. We typed 289 SNPs in the
      critical interval of 8 million basepairs and found a 758 kb interval coding for
      the SPEC2/PDZ-GEF2/ACSL6 genes to be associated with the disease. Using sex and
      genotype-conditioned transmission disequilibrium test analyses, we found that 19
      of the 24 typed markers were associated with the disease and the associations
      were sex-specific. We replicated these findings with an Irish case-control sample
      (657 cases and 414 controls), an Irish parent-proband trio sample (187 families,
      564 subjects), a German nuclear family sample (211 families, 751 subjects) and a
      Pittsburgh nuclear family sample (247 families, 729 subjects). In all four
      samples, we replicated the sex-specific associations at the levels of both
      individual markers and haplotypes using sex- and genotype-conditioned analyses.
      Three risk haplotypes were identified in the five samples, and each haplotype was
      found in at least two samples. Consistent with the discovery of multiple estrogen
      response elements in this region, our data showed that the impact of these
      haplotypes on risk for schizophrenia differed in males and females. From these
      data, we concluded that haplotypes underlying the SPEC2/PDZ-GEF2/ACSL6 region are
      associated with schizophrenia. However, due to the extended high LD in this
      region, we were unable to distinguish whether the association signals came from
      one or more of these genes.

PMID- 17030555
TI  - Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats:
      toxicity is not dependent upon particle size but on surface characteristics.
AB  - Pulmonary toxicology studies in rats demonstrate that nanoparticles are more
      toxic than fine-sized particles of similar chemistry. This study, however,
      provides evidence to contradict this theory. The aims of the study were (1) to
      compare the toxicity of synthetic 50 nm nanoquartz I particles versus (mined) Min
      U-Sil quartz ( approximately 500 nm); the toxicity of synthetic 12 nm nanoquartz
      II particles versus (mined) Min-U-Sil ( approximately 500 nm) versus (synthetic)
      fine-quartz particles (300 nm); and (2) to evaluate the surface activities among
      the samples as they relate to toxicity. Well-characterized samples were tested
      for surface activity and hemolytic potential. In addition, groups of rats were
      instilled with either doses of 1 or 5 mg/kg of carbonyl iron (CI) or various
      alpha-quartz particle types in phosphate-buffered saline solution and
      subsequently assessed using bronchoalveolar lavage fluid biomarkers, cell
      proliferation, and histopathological evaluation of lung tissue at 24 h, 1 week, 1
      month, and 3 months postexposure. Exposures to the various alpha-quartz particles
      produced differential degrees of pulmonary inflammation and cytotoxicity, which
      were not always consistent with particle size but correlated with surface
      activity, particularly hemolytic potential. Lung tissue evaluations of three of
      the quartz samples demonstrated "typical" quartz-related effects--dose-dependent
      lung inflammatory macrophage accumulation responses concomitant with early
      development of pulmonary fibrosis. The various alpha-quartz-related effects were
      similar qualitatively but with different potencies. The range of particle-related
      toxicities and histopathological effects in descending order were nanoscale
      quartz II = Min-U-Sil quartz > fine quartz > nanoscale quartz I > CI particles.
      The results demonstrate that the pulmonary toxicities of alpha-quartz particles
      appear to correlate better with surface activity than particle size and surface
      area.

PMID- 17030556
TI  - Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells.
AB  - The taste system, made up of taste receptor cells clustered in taste buds at the
      surface of the tongue and the soft palate, plays a key role in the decision to
      ingest or reject food and thereby is essential in protecting organisms against
      harmful toxins and in selecting the most appropriate nutrients. To determine if a
      similar chemosensory system exists in the gastrointestinal tract, we used
      immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate
      which taste-signaling molecules are expressed in the intestinal mucosa. The PCR
      data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2
      (PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of
      mice and humans, with the exception of T1r2, which was not detected in the mouse
      and human stomach or in the mouse colon. Using transgenic mice expressing
      enhanced green fluorescent protein under the control of the Trpm5 promoter, we
      found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface
      epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the
      duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express
      PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that
      coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We
      found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3
      in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2.
      The data suggest that these duodenal cells are possibly involved in sensing amino
      acids.

PMID- 17030557
TI  - Determinants of neuropsychological and behavioural outcomes in early childhood
      survivors of congenital heart disease.
AB  - AIMS: To evaluate the relative effect of cyanosis, surgical interventions and
      family processes on neuropsychological and behavioural outcomes in 4-year-old
      survivors of serious congenital heart disease (CHD). METHODS: 90 children with a
      range of cyanotic and acyanotic conditions, who underwent either corrective or
      palliative surgery, completed a neuropsychological and behavioural evaluation.
      Families of participants were also profiled by evaluation of maternal mental
      health, worry, social support, parenting style and family functioning. RESULTS:
      Compromised neuropsychological outcomes were associated with a combination of
      cyanotic conditions and open-heart surgery, but this was not exacerbated by
      having a complex, palliative, status. Both cyanotic and acyanotic conditions were
      associated with specific sensorimotor delays, regardless of method of the
      correction. Only children with complex conditions and palliative interventions
      seemed at risk of poor behavioural outcomes; indeed, children with cyanosis with
      complete repair showed favourable behavioural outcomes compared with controls.
      Multivariate analyses highlighted the sometimes greater relevance of family
      processes (eg parenting style, maternal mental health and worry), rather than
      disease or surgical factors, in predicting especially behavioural outcomes.
      CONCLUSIONS: The findings (1) suggest a more complex relationship between
      cyanosis, surgical methods of correction, neuropsychological and behavioural
      outcomes than previously charted, (2) highlight that family processes may be
      aetiologically more important than disease and surgical factors, and (3) indicate
      specific targets for secondary prevention programmes for this at-risk population.

PMID- 17030558
TI  - Landmarks in understanding the central nervous control of the cardiovascular
      system.
AB  - In this Paton Lecture I have tried to trace the key experiments that have
      developed ideas on how the brain regulates the cardiovascular system. It is a
      personal view and inevitably, owing to constraints on space and time, I have not
      been able to cover areas such as the nucleus tractus solitarius and cardiac vagal
      neurones, although I acknowledge that some may consider the story is incomplete
      without them. Starting with the crucial discovery of vasomotor nerves and
      'vasomotor tone', the patterns of activity in sympathetic nerves which led to the
      important idea of central oscillating networks of neurones are described. I
      discuss how this knowledge has informed current controversies on the origin of
      vasomotor activity in presympathetic neurones in the ventral medulla, which
      identify intrinsic pacemaker activity or synaptic input from multiple oscillators
      as prime mechanisms. I present an emerging view that the role of other regions of
      the brain, in particular supramedullary sites, has been underplayed. These
      regions are pivotal for the non-uniform distribution of cardiac output that is
      unique to each reflex and behavioural state. I discuss the most recent evidence
      for 'central command' neurones that offers a plausible explanation for how these
      patterns of sympathetic activity are achieved. Finally, I stress the importance
      of these current ideas to the understanding of pathological changes in
      sympathetic activity in cardiovascular diseases such as hypertension or
      congestive heart failure.

PMID- 17030559
TI  - Differential regulation of the nitric oxide-cGMP pathway exacerbates
      postischaemic heart injury in stroke-prone hypertensive rats.
AB  - Using a working perfused heart model, we investigated the hypothesis that
      alterations in the NO-cGMP pathway may exacerbate postischaemic mechanical
      dysfunction in the hypertrophied heart. Ischaemia for 25 min followed by
      reperfusion for 30 min produced marked cardiac mechanical dysfunction in both
      stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar
      Kyoto rats (WKY). Exogenous treatment with S-nitroso-N-acetyl-dl-penicillamine
      (SNAP), a NO donor, had beneficial effects on the cardiac dysfunction induced by
      ischaemia-reperfusion (I/R) in the WKY heart, but the cardioprotective effect of
      SNAP was eliminated by guanylyl cyclase inhibitor. Cardiac cGMP levels were
      increased by SNAP or ischaemia in WKY. In contrast, in SHRSP hearts, SNAP could
      not alleviate the cardiac dysfunction caused by I/R. Pre-ischaemia, the cardiac
      cGMP level was significantly higher in SHRSP than in WKY; however, no significant
      difference was found after SNAP and ischaemia. The myocardial Ca(2+)-dependent NO
      synthase (NOS) activity increased at the end of ischaemia in WKY. Conversely, the
      Ca(2+)-independent NOS activity and protein levels were upregulated by I/R in the
      SHRSP myocardium. In the SHRSP hearts, non-selective NOS and selective Ca(2+)
      independent NOS inhibitors or antioxidant treatment alleviated cardiac
      dysfunction caused by I/R. Moreover, mRNA expression and Western blotting
      analysis of cGMP-dependent protein kinase type I showed more deterioration of
      SHRSP hearts compared with WKY. These results suggest that: (1) the NO-dependent
      cardioprotective effect is depressed; and (2) overproduction of NO derived from
      Ca(2+)-independent NOS contributes to postischaemic heart injury in the
      hypertrophied heart of hypertensive status.

PMID- 17030560
TI  - Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal
      muscle.
AB  - Exercise induces a marked increase in interleukin-8 (IL-8) mRNA and protein
      expression within skeletal muscle fibres. Interleukin-8 belongs to a subfamily of
      CXC chemokines containing a Glu-Leu-Arg (ELR) motif. CXC chemokines with ELR
      motifs are potent angiogenic factors in vivo, and IL-8 has been shown to act as
      an angiogenic factor in human microvascular endothelial cells by binding to the
      CXC receptor 2 (CXCR2). In the present study, we examined the expression of the
      interleukin-8 receptor CXCR2 in human skeletal muscle biopsies after concentric
      exercise. Healthy volunteers were randomized to either 3 h of cycle ergometer
      exercise at 60% of maximum oxygen uptake (n = 8) or rest (n = 7). Muscle biopsy
      samples were obtained from the vastus lateralis before exercise (0 h),
      immediately after exercise (3 h), and at 4.5, 6, 9 and 24 h. Skeletal muscle
      CXCR2 mRNA increased significantly in response to exercise (3 and 4.5 h) when
      compared with pre-exercise samples. Expression of the CXCR2 protein was low in
      skeletal muscle biopsies before exercise and at the end of the exercise period (3
      h). However, at 4.5-9 h, an increase in CXCR2 protein was seen in the vascular
      endothelium, and also slightly within the muscle fibres, as determined by
      immunohistochemistry. The present study demonstrates that concentric exercise
      induces CXCR2 mRNA and protein expression in the vascular endothelial cells of
      the muscle fibres. These findings suggest that muscle-derived IL-8 may act
      locally to stimulate angiogenesis through CXCR2 receptor signalling.

PMID- 17030561
TI  - First-in-first-out item replacement in a model of short-term memory based on
      persistent spiking.
AB  - Persistent neuronal firing has been modeled in relation to observed brain
      rhythms, especially to theta oscillations recorded in behaving animals. Models of
      short-term memory that are based on such persistent firing properties of specific
      neurons can meet the requirements of spike-timing-dependent potentiation of
      synaptic strengths during the encoding of a temporal sequence of spike patterns.
      We show that such a spiking buffer can be simulated with integrate-and-fire
      neurons that include a leak current even when different numbers of spikes
      represent successive items. We propose a mechanism that successfully replaces
      items in the buffer in first-in-first-out (FIFO) order when the distribution of
      spike density in a theta cycle is asymmetric, as found in experimental data. We
      predict effects on the function and capacity of the buffer model caused by
      changes in modeled theta cycle duration, the timing of input to the buffer, the
      strength of recurrent inhibition, and the strength and timing of after
      hyperpolarization and after-depolarization (ADP). Shifts of input timing or
      changes in ADP parameters can enable the reverse-order buffering of items, with
      FIFO replacement in a full buffer. As noise increases, the simulated buffer
      provides robust output that may underlie episodic encoding.

PMID- 17030562
TI  - Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type
      1 microbicides with the human cervicovaginal mucosa modeled ex vivo.
AB  - Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to
      reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of
      this strategy depends upon the selection of formulations compatible with the
      natural vaginal mucosal barrier. This study applied ex vivo-modeled human
      cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti
      HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the
      counter (OTC) vaginal products for their impact on inflammatory mediators
      regarded as potential HIV-1-enhancing risk factors. We assessed product-induced
      imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL
      1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis
      factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage
      inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate
      monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel
      formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel
      and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes
      in any inflammatory biomarker. In contrast, OTC vaginal cleansing and
      contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated
      similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha,
      IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal
      cleansing and contraceptive films; however, MIP-3alpha was significantly elevated
      by the N-9-based film only (P < 0.01). Although both films increased
      extracellular IL-1RA, the cleansing film only significantly elevated the IL
      1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P
      < 0.05), which has anti-inflammatory intracrine functions. This study identifies
      immunoinflammatory biomarkers that can discriminate between formulations better
      than toxicity assays and should be clinically validated in relevance to the risk
      of HIV-1 acquisition.

PMID- 17030563
TI  - Novel alpha interferon (IFN-alpha) variant with improved inhibitory activity
      against hepatitis C virus genotype 1 replication compared to IFN-alpha2b therapy
      in a subgenomic replicon system.
AB  - Hepatitis C virus (HCV) treatment is based on the association of pegylated alpha
      interferon (IFN-alpha) and ribavirin. To improve the level of sustained
      virological response to treatment, especially in patients infected with HCV
      genotype 1, new IFNs with improved efficacy and toxicity profiles may be
      developed. In this report, we show that, in the BM4-5 cell line harboring an HCV
      subgenomic replicon, a novel and naturally occurring human IFN-alpha17 variant,
      GEA007.1, which was discovered by using an original population genetics-based
      drug discovery approach, inhibits HCV genotype 1 RNA replication more efficiently
      than does IFN-alpha2b. Moreover, we show that complete viral clearance is
      obtained in BM4-5 cells after long-term treatment with GEA007.1, while HCV
      subgenomic RNA is still detected in cells treated with other IFN-alpha variants
      or with standard IFN-alpha2b. Eventually, we demonstrate that the better
      inhibitory activity of GEA007.1 compared to that of standard IFN-alpha is likely
      to be due to stronger and faster activation of the JAK-STAT signaling pathway and
      to broader expression of IFN-alpha-responsive genes in cells. Our results
      demonstrate a superior inhibitory activity of GEA007.1 over that of IFN-alpha2b
      in the HCV replicon system. Clinical trials are required to determine whether
      GEA007.1 could be a potent "next generation" IFN for the treatment of HCV
      infection, especially in nonresponders or relapsing patients infected with HCV
      genotype 1 who currently represent a clinical unmet need.

PMID- 17030564
TI  - Modification of enrofloxacin treatment regimens for poultry experimentally
      infected with Salmonella enterica serovar Typhimurium DT104 to minimize selection
      of resistance.
AB  - We hypothesized that higher doses of fluoroquinolones for a shorter duration
      could maintain efficacy (as measured by reduction in bacterial count) while
      reducing selection in chickens of bacteria with reduced susceptibility. Chicks
      were infected with Salmonella enterica serovar Typhimurium DT104 and treated 1
      week later with enrofloxacin at the recommended dose for 5 days (water dose
      adjusted to give 10 mg/kg of body weight of birds or equivalence, i.e., water at
      50 ppm) or at 2.5 or 5 times the recommended dose for 2 days or 1 day,
      respectively. The dose was delivered continuously (ppm) or pulsed in the water
      (mg/kg) or by gavage (mg/kg). In vitro in sera, increasing concentrations of 0.5
      to 8 microg/ml enrofloxacin correlated with increased activity. In vivo, the
      efficacy of the 1-day treatment was significantly less than that of the 2- and 5
      day treatments. The 2-day treatments showed efficacy similar to that of the 5-day
      treatment in all but one repeat treatment group and significantly (P < 0.01)
      reduced the Salmonella counts. Dosing at 2.5x the recommended dose and pulsed
      dosing both increased the peak antibiotic concentrations in cecal contents,
      liver, lung, and sera as determined by high-pressure liquid chromatography. There
      was limited evidence that shorter treatment regimens (in particular the 1-day
      regimen) selected for fewer strains with reduced susceptibility. In conclusion,
      the 2-day treatment would overall require a shorter withholding time than the 5
      day treatment and, in view of the increased peak antibiotic concentrations, may
      give rise to improved efficacy, in particular for treating respiratory and
      systemic infections. However, it would be necessary to validate the 2-day regimen
      in a field situation and in particular against respiratory and systemic
      infections to validate or refute this hypothesis.

PMID- 17030565
TI  - Quantitative analysis of tpr gene expression in Treponema pallidum isolates:
      Differences among isolates and correlation with T-cell responsiveness in
      experimental syphilis.
AB  - Transcriptional analysis of the tpr genes in Treponema pallidum subsp. pallidum
      (referred to here as simply T. pallidum) has been limited to date, and yet the
      expression of members of this gene family is likely relevant to the pathogenesis
      of syphilis. Recently, immunological studies and semiquantitative mRNA analysis
      led to the hypothesis of the modulation of tpr gene transcription during
      infection and suggested that various strains of T. pallidum might differentially
      express these genes. In this study we developed a real-time amplification assay
      to quantify the tpr mRNAs with respect to the 47-kDa lipoprotein message and to
      compare transcript levels among four different strains of T. pallidum. In
      addition, we analyzed the lymphocyte responsiveness pattern toward the Tpr
      antigens in late experimental syphilis to identify tpr genes that had been
      expressed during the course of infection. The T-cell response has been implicated
      in clearance of treponemes from early lesions, and some of the Tprs were
      identified as strong targets of the cellular immune response. We show that
      message for many of the tpr genes can be detected in treponemes harvested at the
      peak of early infection. Interestingly, tprK seems to be preferentially expressed
      in almost every strain, and it is uniformly the target of the strongest cellular
      immune response. These studies demonstrate the differential expression of certain
      tpr genes among strains of T. pallidum, and further studies are needed to explore
      the relationship between tpr gene expression and the clinical course of syphilis
      in infected individuals.

PMID- 17030566
TI  - Identification of genes involved in the expression of atypical
      lipooligosaccharide structures from a second class of Haemophilus ducreyi.
AB  - Haemophilus ducreyi is a gram-negative bacterium that is the causative agent of
      chancroid. Strain 35000HP has been well characterized and is representative of
      the majority of H. ducreyi strains. Strain 35000HP produces a lipooligosaccharide
      (LOS) that contains D-glycero-D-manno-heptose in the main oligosaccharide chain
      extension; the lbgB gene has been shown to encode the DD-heptosyltransferase. The
      lbgB gene is found in a gene cluster together with the lbgA gene, which encodes
      for the galactosyltransferase I. These two genes are flanked by two housekeeping
      genes, rpmE and xthA, encoding the ribosomal protein L31 and the exonuclease III,
      respectively. Recently, a second group of H. ducreyi strains have been
      identified. Strain 33921, a representative of the class II strains, produces an
      LOS that lacks DD-heptose in the oligosaccharide portion of its LOS. To better
      understand the biosynthesis of the DD-heptose-deficient 33921 LOS, we cloned and
      sequenced the corresponding lbgAB genomic region from strain 33921. Similar to
      strain 35000HP, the 33921 genome contains xthA and rpmE. However, between these
      two genes we identified genes encoding two putative glycosyltransferases that
      were not highly homologous to the 35000HP lbgAB genes. In this study, we
      demonstrate that the product of one of these genes encodes a
      galactosyltransferase. In addition, dot blot hybridization determined that 3 of
      35 strains tested had the atypical transferases present, as did 4 strains
      characterized as class II strains by other criterion. These data indicate that
      the lbgAB genes can serve as one indicator of the classification of H. ducreyi
      strains.

PMID- 17030567
TI  - Signature-tagged transposon mutagenesis identifies novel Mycobacterium
      tuberculosis genes involved in the parasitism of human macrophages.
AB  - Using signature-tagged transposon mutagenesis, we isolated 23 Mycobacterium
      tuberculosis mutants, corresponding to 21 genes or genetic regions, attenuated in
      their ability to parasitize human macrophages. Mutants disrupted in the ABC
      transporter-encoding genes Rv0986 and Rv0987 were further characterized as being
      impaired in their ability to bind to host cells.

PMID- 17030568
TI  - A Mycobacterium marinum mel2 mutant is defective for growth in macrophages that
      produce reactive oxygen and reactive nitrogen species.
AB  - Macrophages produce reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) in response to bacterial infections. Mycobacteria are relatively resistant
      to ROS, but RNS inhibit growth of, and possibly even kill, mycobacteria in
      activated macrophages. We recently constructed a Mycobacterium marinum mel2 locus
      mutant, which is known to affect macrophage infection. We found previously that
      the mel2 locus confers resistance to ROS and RNS in laboratory medium, suggesting
      that this locus might play a similar role during growth in macrophages. Since
      J774A.1 murine macrophages produce high levels of ROS and RNS upon activation
      with gamma interferon (IFN-gamma), we examined the effects of IFN-gamma on ROS
      and RNS production by these cells as well as the effects on growth of M. marinum
      in these cells. We found that an M. marinum mutant with mutation of the first
      gene in the mel2 locus, melF, is defective for growth in IFN-gamma-plus
      lipopolysaccharide-treated J774A.1 cells and that this defect is abrogated by the
      presence of either inhibitors of nitric oxide synthase or ROS scavengers.
      Furthermore, the M. marinum melF mutant displays a defect at late stages in the
      mouse footpad model of infection. These phenotypic characteristics could be
      complemented fully by the entire mel2 locus but only partially by the presence of
      melF alone, supporting data suggesting that this insertion mutation has polar
      effects on downstream genes in the mel2 locus. These observations demonstrate
      that the M. marinum mel2 locus plays a role in resistance to ROS and RNS produced
      by activated macrophages.

PMID- 17030569
TI  - V beta1+ J beta1.1+/V alpha2+ J alpha49+ CD4+ T cells mediate resistance against
      infection with Blastomyces dermatitidis.
AB  - Immunization with a cell wall/membrane (CW/M) and yeast cytosol extract (YCE)
      crude antigen from Blastomyces dermatitidis confers T-cell-mediated resistance
      against lethal experimental infection in mice. We isolated and characterized T
      cells that recognize components of these protective antigens and mediate
      protection. CD4+ T-cell clones elicited with CW/M antigen adoptively transferred
      protective immunity when they expressed a V alpha2+ J alpha49+/V beta1+ J
      beta1.1+ heterodimeric T-cell receptor (TCR) and produced high levels of gamma
      interferon (IFN-gamma). In contrast, V beta8.1/8.2+ CD4+ T-cell clones that were
      reactive against CW/M and YCE antigens and produced little or no IFN-gamma either
      failed to mediate protection or exacerbated the infection depending on the level
      of interleukin-5 expression. Thus, the outgrowth of protective T-cell clones
      against immunodominant antigens of B. dermatitidis is biased by a combination of
      the TCR repertoire and Th1 cytokine production.

PMID- 17030570
TI  - Biological Trojan horse: Antigen 43 provides specific bacterial uptake and
      survival in human neutrophils.
AB  - Escherichia coli is a versatile pathogen causing millions of infections in humans
      every year. This bacterium can form multicellular aggregates when it expresses a
      self-associating protein, antigen 43 (Ag43), on its surface. We have discovered
      that Ag43-expressing E. coli cells are efficiently taken up by human defense
      cells, polymorphonuclear neutrophils (PMNs), in an opsonin-independent manner.
      Surprisingly, the phagocytosed bacteria were not immediately killed but resided
      as tight aggregates within the PMNs. Our observations indicate that Ag43-mediated
      uptake and survival in PMNs constitute a mechanism to subvert one of the primary
      defense mechanisms of the human body.

PMID- 17030571
TI  - Role of the wbt locus of Francisella tularensis in lipopolysaccharide O-antigen
      biogenesis and pathogenicity.
AB  - Francisella tularensis is a highly infectious bacterial pathogen, responsible for
      the zoonotic disease tularemia. We screened a bank of transposon insertion
      mutants of F. tularensis subsp. holarctica LVS for colony morphology alterations
      and selected a mutant with a transposon insertion in wbtA, the first gene of the
      predicted lipopolysaccharide O-antigen gene cluster. Inactivation of wbtA led to
      the complete loss of O antigen, conferred serum sensitivity, impaired
      intracellular replication, and severely attenuated virulence in the mouse model.
      Notably, this mutant afforded protection against a challenge against virulent
      LVS.

PMID- 17030572
TI  - The SecA2 secretion factor of Mycobacterium tuberculosis promotes growth in
      macrophages and inhibits the host immune response.
AB  - The SecA protein is present in all bacteria, and it is a central component of the
      general Sec-dependent protein export pathway. An unusual property of
      Mycobacterium tuberculosis is the presence of two SecA proteins: SecA1, the
      essential "housekeeping" SecA, and SecA2, the accessory secretion factor. Here,
      we report that a DeltasecA2 mutant of M. tuberculosis was defective for growth in
      the early stages of low-dose aerosol infection of C57BL/6 mice, a time during
      which the bacillus is primarily replicating in macrophages. Consistent with this
      in vivo phenotype, we found that the DeltasecA2 mutant was defective for growth
      in macrophages from C57BL/6 mice. The DeltasecA2 mutant was also attenuated for
      growth in macrophages from phox(-/-) mice and from NOS2(-/-) mice. These mice are
      defective in the reactive oxygen intermediate (ROI)-generating phagocyte oxidase
      and the reactive nitrogen intermediate (RNI)-generating inducible nitric oxide
      synthase, respectively. This indicated a role for SecA2 in the intracellular
      growth of M. tuberculosis that is independent of protecting against these ROIs or
      RNIs. Macrophages infected with the DeltasecA2 mutant produced higher levels of
      tumor necrosis factor alpha, interleukin-6, RNI, and gamma interferon-induced
      major histocompatibility complex class II. This demonstrated a function for M.
      tuberculosis SecA2 in suppressing macrophage immune responses, which could
      explain the role of SecA2 in intracellular growth. Our results provide another
      example of a relationship between M. tuberculosis virulence and inhibition of the
      host immune response.

PMID- 17030573
TI  - Long-term staphylococcal enterotoxin C1 exposure induces soluble factor-mediated
      immunosuppression by bovine CD4+ and CD8+ T cells.
AB  - Regulatory T cells (T(regs)) help control the development and maintenance of
      protective immunity and can lead to aberrant immune responses to some pathogens.
      Several lines of evidence suggest that T(regs) are induced by exposure to
      superantigens (SAgs) in vitro or in vivo. In this study, bovine peripheral blood
      mononuclear cells (PBMC) were exposed in vitro to a relatively low dose (5 ng/ml)
      of staphylococcal enterotoxin C1 (SEC1) for up to 10 days. Upon stimulation, CD4+
      and CD8+ T cells initially proliferated at similar rates. Subsequently, from days
      6 through 10, most CD4+ and CD8+ T cells proliferated regardless of Vbeta
      specificity, but the proliferation of CD8+ T cells occurred more vigorously. The
      transcription of CD25 and CD152 genes increased, whereas that of interleukin-2
      (IL-2) decreased. gammadelta T cells appeared to be unresponsive. An increase in
      the transcription of IL-10 and transforming growth factor beta (TGF-beta) genes
      in SEC1-stimulated cultures was attributed to the CD4+ CD25+ T-cell
      subpopulation. The expression of Foxp3 mRNA also increased and was accompanied by
      the upregulation of CD152 and the downregulation of IL-2 transcription,
      suggesting that cells in this subpopulation are T(regs). Functionally, SEC1
      stimulated CD4+ T cells suppressed the proliferation of naive PBMC in response to
      heat-killed-fixed Staphylococcus aureus. The suppression was partially mediated
      by IL-10 and TGF-beta, another characteristic of certain types of T(regs.) The
      CD8+ T-cell population also suppressed naive PBMC through another mechanism not
      mediated by IL-10 or TGF-beta. These results provide further insight into the
      potential mechanisms by which SAgs could contribute to evasion of the immune
      response, affecting the outcome of infection or colonization.

PMID- 17030574
TI  - Up-regulation of gamma interferon receptor expression due to Chlamydia-toll-like
      receptor interaction does not enhance signal transducer and activator of
      transcription 1 signaling.
AB  - Gamma interferon (IFN-gamma)-induced indoleamine dioxygenase (IDO), which
      inhibits chlamydial replication by reducing the availability of tryptophan, is up
      regulated by interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF
      alpha). The mechanisms by which this occurs include an increase in the synthesis
      of interferon regulatory factor-1 as well as a nuclear factor-kappaB (NF-kappaB)
      dependent increase in the expression of IFN-gamma receptors (IFN-gammaR).
      Although Chlamydia is susceptible to IDO, it up-regulates IFN-gammaR expression
      to a greater degree than either IL-1beta or TNF-alpha, perhaps through
      interaction with Toll-like receptors (TLR). The purpose of this study was to
      determine the mechanism by which Chlamydia psittaci up-regulates IFN-gammaR
      expression and evaluate this effect on IDO induction. Infection of HEK 293 cells
      with C. psittaci increased IFN-gammaR expression only in cells expressing either
      TLR2 or TLR4 and the adaptor protein MD-2. In addition, up-regulation of IFN
      gammaR expression in Chlamydia-infected HeLa cells could be blocked either by
      neutralizing TLRs with anti-TLR2 and/or anti-TLR4 or by inhibiting NF-kappaB
      transactivation with a proteasome inhibitor. Although the newly expressed IFN
      gammaR in Chlamydia-infected cells were capable of binding IFN-gamma, they did
      not enhance IFN-gamma-induced IDO activity in a manner similar to those observed
      for IL-1beta and TNF-alpha. Instead, IDO activation in Chlamydia-infected cells
      was no different than that induced in uninfected cells, despite the increase in
      IFN-gammaR expression. Furthermore, the amount of IFN-gamma-induced signal
      transducer and activator of transcription 1 (STAT-1) activation in infected cells
      paralleled that observed in uninfected cells, suggesting that STAT-1 activation
      by these newly expressed receptors was impaired.

PMID- 17030575
TI  - Role of neutrophils in invasive aspergillosis.

PMID- 17030576
TI  - The 13C4 monoclonal antibody that neutralizes Shiga toxin Type 1 (Stx1)
      recognizes three regions on the Stx1 B subunit and prevents Stx1 from binding to
      its eukaryotic receptor globotriaosylceramide.
AB  - The 13C4 monoclonal antibody (MAb) recognizes the B subunit of Stx1 (StxB1) and
      neutralizes the cytotoxic and lethal activities of Stx1. However, this MAb does
      not bind to the B polypeptide of Stx2, despite the 73% amino acid sequence
      similarity between StxB1 and StxB2. When we compared the amino acid sequences of
      StxB1 and StxB2, we noted three regions of dissimilarity (amino acids 1 to 6, 25
      to 32, and 54 to 61) located near each other on the crystal structure of StxB1.
      To identify the 13C4 epitope, we generated seven Stx1/Stx2 B chimeric
      polypeptides that contained one, two, or three of the dissimilar StxB1 regions.
      The 13C4 MAb reacted strongly with StxB1 and the triple-chimeric B subunit but
      not with the other chimeras. Mice immunized with the triple-chimeric B subunit
      survived a lethal challenge with Stx1 but not Stx2, substantiating the identified
      regions as the 13C4 MAb epitope and suggesting that the incorporation of this
      epitope into StxB2 altered sites necessary for anti-Stx2-neutralizing Ab
      production. Next, single amino acid substitutions were made in StxB1 to mimic
      Stx1d, a variant not recognized by the 13C4 MAb. The 13C4 MAb reacted strongly to
      StxB1 with the T1A or G25A mutations but not with the N55T change. Finally, we
      found that the 13C4 MAb blocked the binding of Stx1 to its receptor,
      globotriaosyl ceramide. Taken together, these results indicate that the 13C4 MAb
      prevents the interaction of Stx1 with its receptor by binding three nonlinear
      regions of the molecule that span receptor recognition sites on StxB1, one of
      which includes the essential residue 55N.

PMID- 17030577
TI  - Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative
      stress.
AB  - Neutrophil-activating protein (NapA) has been well documented to play roles in
      human neutrophil recruitment and in stimulating host cell production of reactive
      oxygen intermediates (ROI). A separate role for NapA in combating oxidative
      stress within H. pylori was implied by studies of various H. pylori mutant
      strains. Here, physiological analysis of a napA strain was the approach used to
      assess the iron-sequestering and stress resistance roles of NapA, its role in
      preventing oxidative DNA damage, and its importance to mouse colonization. The
      napA strain was more sensitive to oxidative stress reagents and to oxygen, and it
      contained fourfold more intracellular free iron and more damaged DNA than the
      parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not,
      presumably linking iron levels sensed by NapA to DNA damage protection. Despite
      its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed
      normal (like that of the wild type) mouse colonization efficiency in the
      conventional in vivo assay. By use of a modified mouse inoculation protocol
      whereby nonviable H. pylori is first inoculated into mice, followed by (live)
      bacterial strain administration, an in vivo role for NapA in colonization
      efficiency could be demonstrated. NapA is the critical component responsible for
      inducing host-mediated ROI production, thus inhibiting colonization by the napA
      strain. An animal colonization experiment with a mixed-strain infection protocol
      further demonstrated that the napA strain has significantly decreased ability to
      survive when competing with the wild type. H. pylori NapA has unique and separate
      roles in gastric pathogenesis.

PMID- 17030578
TI  - Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and
      meninges after meningococcal infection.
AB  - Antimicrobial peptides are present in most living species and constitute
      important effector molecules of innate immunity. Recently, we and others have
      detected antimicrobial peptides in the brain. This is an organ that is rarely
      infected, which has mainly been ascribed to the protective functions of the blood
      brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB
      and meninges are not known, we hypothesized that antimicrobial peptides could
      play a role in these barriers. We addressed this hypothesis by infecting mice
      with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed
      for expression of the antimicrobial peptide CRAMP by immunohistochemistry in
      combination with confocal microscopy. After infection, we observed induction of
      CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore
      the functional role of CRAMP in meningococcal disease, we infected mice deficient
      of the CRAMP gene. Even though CRAMP did not appear to protect the brain from
      invasion of meningococci, CRAMP knockout mice were more susceptible to
      meningococcal infection than wild-type mice and exhibited increased meningococcal
      growth in blood, liver, and spleen. Moreover, we could demonstrate that
      carbonate, a compound that accumulates in the circulation during metabolic
      acidosis, makes meningococci more susceptible to CRAMP.

PMID- 17030579
TI  - Helicobacter pylori HP1512 is a nickel-responsive NikR-regulated outer membrane
      protein.
AB  - Helicobacter pylori is dependent upon the production of the highly abundant and
      active metalloenzyme urease for colonization of the human stomach. Thus, H.
      pylori has an absolute requirement for the transition metal nickel, a required
      cofactor for urease. To investigate the contribution of genes that are factors in
      this process, microarray analysis comparing the transcriptome of wild-type H.
      pylori 26695 cultured in brucella broth containing fetal calf serum (BBF) alone
      or supplemented with 100 microM NiCl(2) suggested that HP1512 is repressed in the
      presence of 100 microM supplemental nickel. When measured by comparative real
      time quantitative PCR (qPCR), HP1512 transcription was reduced 43-fold relative
      to the value for the wild type when cultured in BBF supplemented with 10 microM
      NiCl(2). When grown in unsupplemented BBF, urease activity of an HP1512::cat
      mutant was significantly reduced compared to the wild type, 4.9 +/- 0.5
      micromol/min/mg of protein (n = 7) and 17.1 +/- 4.9 micromol/min/mg of protein (n
      = 13), respectively (P < 0.0001). In silico analysis of the HP1511-HP1512 (HP1511
      1512) intergenic region identified a putative NikR operator upstream of HP1512.
      Gel shift analysis with purified recombinant NikR verified nickel-dependent
      binding of H. pylori NikR to the HP1511-1512 intergenic region. Furthermore,
      comparative real-time qPCR of four nickel-related genes suggests that mutation of
      HP1512 results in reduced intracellular nickel concentration relative to wild
      type H. pylori 26695. Taken together, these data suggest that HP1512 encodes a
      NikR-nickel-regulated outer membrane protein.

PMID- 17030580
TI  - Microneedle-based intradermal delivery of the anthrax recombinant protective
      antigen vaccine.
AB  - The recombinant protective antigen (rPA) of Bacillus anthracis is a promising
      anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing
      antibody titers in rabbits following delivery of various doses of vaccine by
      microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection
      using conventional needles. Intradermal delivery required less antigen to induce
      levels of antibody similar to those produced via i.m. injection during the first
      2 weeks following primary and booster inoculation. This dose-sparing effect was
      less evident at the later stages of the immune response. Rabbits immunized i.d.
      with 10 mug of rPA displayed 100% protection from aerosol spore challenge, while
      i.m. injection of the same dose provided slightly lower protection (71%). Groups
      immunized with lower antigen doses were partially protected (13 to 29%)
      regardless of the mode of administration. Overall, our results suggest rPA
      formulated with aluminum adjuvant and administered to the skin by a microneedle
      based device is as efficacious as i.m. vaccination.

PMID- 17030581
TI  - Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp.
AB  - Relapsing fever Borrelia spp. undergo antigenic variation, achieve high levels in
      blood, and require rapid production of immunoglobulin M (IgM) for clearance.
      MyD88-deficient mice display defective clearance of many pathogens; however, the
      IgM response to persistent infection is essentially normal. Therefore, MyD88(-/-)
      mice provided a unique opportunity to study the effect of nonantibody, innate
      host defenses to relapsing fever Borrelia. Infected MyD88(-/-) mice harbored
      extremely high levels of B. hermsii in the blood compared to wild-type
      littermates. In the comparison of MyD88(-/-) mice and B- and T-cell-deficient
      scid mice, two features stood out: (i) bacterial numbers in blood were at least
      10-fold greater in MyD88(-/-) mice than scid mice, even though the production of
      IgM still occurred in MyD88(-/-) mice; and (ii) many of the MyD88(-/-) mice were
      able to exert partial clearance, although with delayed kinetics relative to wild
      type mice, a feature not seen in scid mice. Further analysis revealed a delay in
      the IgM response to lipoproteins expressed by the original inoculum; however, by
      6 days of infection antibodies were produced in MyD88(-/-) mice that could clear
      spirochetemia in scid mice. While these results indicated that the production of
      IgM was delayed in MyD88(-/-) mice, they also point to a second, antibody
      independent role for MyD88 signaling in host defense to relapsing fever Borrelia.
      This second defect was apparent only when antibody levels were limiting.

PMID- 17030582
TI  - GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to
      Aspergillus fumigatus virulence.
AB  - Gliotoxin is a nonribosomal peptide produced by Aspergillus fumigatus. This
      compound has been proposed as an A. fumigatus virulence factor due to its
      cytotoxic, genotoxic, and apoptotic properties. Recent identification of the
      gliotoxin gene cluster identified several genes (gli genes) likely involved in
      gliotoxin production, including gliZ, encoding a putative Zn(2)Cys(6) binuclear
      transcription factor. Replacement of gliZ with a marker gene (DeltagliZ) resulted
      in no detectable gliotoxin production and loss of gene expression of other gli
      cluster genes. Placement of multiple copies of gliZ in the genome increased
      gliotoxin production. Using endpoint survival data, the DeltagliZ and a multiple
      copy gliZ strain were not statistically different from the wild type in a murine
      pulmonary model; however, both the wild-type and the multiple-copy gliZ strain
      were more virulent than DeltalaeA (a mutant reduced in production of gliotoxin
      and other toxins). A flow-cytometric analysis of polymorphonuclear leukocytes
      (PMNs) exposed to supernatants from wild-type, DeltagliZ, complemented DeltagliZ,
      and DeltalaeA strains supported a role for gliotoxin in apoptotic but not
      necrotic PMN cell death. This may indicate that several secondary metabolites are
      involved in A. fumigatus virulence.

PMID- 17030583
TI  - Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor,
      receptor-like protein tyrosine phosphatase beta, is required for intoxication in
      AZ-521 Cells.
AB  - Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on
      epithelial cells through different cellular events: one involves pore formation,
      leading to vacuolation, mitochondrial damage, and apoptosis, and the second
      involves cell signaling, resulting in stimulation of proinflammatory responses
      and cell detachment. Our recent data demonstrated that VacA uses receptor-like
      protein tyrosine phosphatase beta (RPTPbeta) as a receptor, of which five
      residues (QTTQP) at positions 747 to 751 are involved in binding. In AZ-521
      cells, which mainly express RPTPbeta, VacA, after binding to RPTPbeta in non
      lipid raft microdomains on the cell surface, is localized with RPTPbeta in lipid
      rafts in a temperature- and VacA concentration-dependent process. Methyl-beta
      cyclodextrin (MCD) did not block binding to RPTPbeta but inhibited translocation
      of VacA with RPTPbeta to lipid rafts and all subsequent events. On the other
      hand, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), which disrupts anion
      channels, did not inhibit translocation of VacA to lipid rafts or VacA-induced
      activation of p38 mitogen-activated protein (MAP) kinase, but inhibited VacA
      internalization followed by vacuolation. Thus, p38 MAP kinase activation did not
      appear to be required for internalization. In contrast, phosphatidylinositol
      specific phospholipase C (PI-PLC) inhibited translocation, as well as p38 MAP
      kinase/ATF-2 activation, internalization, and VacA-induced vacuolation. Neither
      NPPB nor PI-PLC affected VacA binding to cells and to its receptor, RPTPbeta.
      Thus, receptor-dependent translocation of VacA to lipid rafts is critical for
      signaling pathways leading to p38 MAP kinase/ATF-2 activation and vacuolation.

PMID- 17030584
TI  - A linear peptide containing minimal T- and B-cell epitopes of Plasmodium
      falciparum circumsporozoite protein elicits protection against transgenic
      sporozoite challenge.
AB  - An effective malaria vaccine is needed to address the public health tragedy
      resulting from the high levels of morbidity and mortality caused by Plasmodium
      parasites. The first protective immune mechanism identified in the irradiated
      sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was
      sporozoite-neutralizing antibody specific for the repeat region of the surface
      circumsporozoite (CS) protein. Previous phase I studies demonstrated that a
      branched peptide containing minimal T- and B-cell epitopes of Plasmodium
      falciparum CS protein elicited antirepeat antibody and CD4(+)-T-cell responses
      comparable to those observed in volunteers immunized with irradiated P.
      falciparum sporozoites. The current study compares the immunogenicity of linear
      versus tetrabranched peptides containing the same minimal T- and B-cell epitopes,
      T1BT*, comprised of a CS-derived universal Th epitope (T*) synthesized in tandem
      with the T1 and B repeats of P. falciparum CS protein. A simple 48-mer linear
      synthetic peptide was found to elicit antisporozoite antibody and gamma
      interferon-secreting T-cell responses comparable to the more complex
      tetrabranched peptides in inbred strains of mice. The linear peptide was also
      immunogenic in outbred nonhuman primates (Aotus nancymaae), eliciting antibody
      titers equivalent to those induced by tetrabranched peptides. Importantly, the 48
      mer linear peptide administered in adjuvants suitable for human use elicited
      antibody-mediated protection against challenge with rodent malaria transgenic
      sporozoites expressing P. falciparum CS repeats. These findings support further
      evaluation of linear peptides as economical, safe, and readily produced malaria
      vaccines for the one-third of the world's population at risk of malaria
      infection.

PMID- 17030585
TI  - Surfactant protein D increases fusion of Mycobacterium tuberculosis-containing
      phagosomes with lysosomes in human macrophages.
AB  - Lung surfactant protein D (SP-D) binds to Mycobacterium tuberculosis surface
      lipoarabinomannan and results in bacterial agglutination, reduced uptake, and
      inhibition of growth in human macrophages. Here we show that SP-D limits the
      intracellular growth of bacilli in macrophages by increasing phagosome-lysosome
      fusion but not by generating a respiratory burst.

PMID- 17030586
TI  - Diffusion anisotropy of the cervical cord is strictly associated with disability
      in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      with severe cervical cord damage due to degeneration of the corticospinal tracts
      and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT
      MRI) allows the measurement of quantities reflecting the size (such as mean
      diffusivity) and orientation (such as fractional anisotropy) of water-filled
      spaces in biological tissues. METHODS: Mean diffusivity and fractional anisotropy
      histograms from the cervical cord of patients with ALS were obtained to: (1)
      quantify the extent of tissue damage in this critical central nervous system
      region; and (2) investigate the magnitude of the correlation of cervical cord DT
      MRI metrics with patients' disability and tissue damage along the brain portion
      of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained
      from 28 patients with ALS and 20 age-matched and sex-matched controls. Cord mean
      diffusivity and fractional anisotropy histograms were produced and the cord cross
      sectional area was measured. Average mean diffusivity and fractional anisotropy
      along the brain portion of the corticospinal tracts were also measured. RESULTS:
      Compared with controls, patients with ALS had significantly lower mean fractional
      anisotropy (p = 0.002) and cord cross-sectional area (p<0.001). Mean diffusivity
      histogram-derived metrics did not differ between the two groups. A strong
      correlation was found between mean cord fractional anisotropy and the ALS
      Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional
      anisotropy values correlated moderately (r = 0.37, p = 0.05). CONCLUSIONS:
      Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be
      graded. The conventional and DT MRI changes found are compatible with the
      presence of neuroaxonal loss and reactive gliosis, with a heterogeneous
      distribution of the pathological process between the brain and the cord. The
      correlation found between cord fractional anisotropy and disability suggests that
      DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.

PMID- 17030587
TI  - Visual hallucinations and agitation in Alzheimer's disease due to memantine:
      report of three cases.

PMID- 17030588
TI  - Patterns of reoccurrence of segmental dystonia after discontinuation of deep
      brain stimulation.
AB  - The pattern of reoccurrence of symptoms after discontinuation of deep brain
      stimulation (DBS) has not been systematically studied in dystonia. Eight patients
      (mean age (SD) 53.8 (14.4) years) with segmental dystonia at a mean follow-up of
      11.3 (4.2) months were studied after implantation of bilateral DBS electrodes in
      the internal globus pallidus using a standard video protocol and clinical rating
      scales, immediately and at 2 and 4 h after switching off DBS. Dystonic signs
      returned sequentially, with a rapid worsening of phasic and a slower worsening of
      tonic dystonic components. In all patients, phasic dystonic features appeared
      within a few minutes, whereas the tonic elements of dystonia reoccurred with a
      more variable delay. Differential clinical effects when withdrawing DBS might
      reflect its influence on different pathophysiological mechanisms in dystonia.

PMID- 17030589
TI  - Screening designs for drug development.
AB  - We propose drug screening designs based on a Bayesian decision-theoretic
      approach. The discussion is motivated by screening designs for phase II studies.
      The proposed screening designs allow consideration of multiple treatments
      simultaneously. In each period, new treatments can arise and currently considered
      treatments can be dropped. Once a treatment is removed from the phase II
      screening trial, a terminal decision is made about abandoning the treatment or
      recommending it for a future confirmatory phase III study. The decision about
      dropping treatments from the active set is a sequential stopping decision. We
      propose a solution based on decision boundaries in the space of marginal
      posterior moments for the unknown parameter of interest that relates to each
      treatment. We present a Monte Carlo simulation algorithm to implement the
      proposed approach. We provide an implementation of the proposed method as an easy
      to use R library available for public domain download
      (http://www.stat.rice.edu/~rusi/ or http://odin.mdacc.tmc.edu/~pm/).

PMID- 17030591
TI  - Surgical manifestations of Paget's disease.
AB  - Paget's disease is a chronic, nonmetabolic bone disorder characterized by
      increased bone resorption, bone formation, and remodeling. This unbalanced
      process may lead to osseous deformities, structural weakness, and altered joint
      biomechanics, all of which can make surgical reconstruction difficult. Although
      few patients with Paget's disease require surgical treatment, successful surgical
      management of severe orthopaedic complications has improved the quality of life
      for these patients. Surgical options include osteotomy to correct long-bone
      deformity and arthroplasty to restore altered joint mechanics. Patients are at
      increased risk for surgical complications, such as blood loss and heterotopic
      bone formation. Issues relating to the surgical management of patients with
      Paget's disease include appropriate preoperative diagnosis, technical challenges
      of surgery, and strategies to improve the long-term outcome of surgical
      intervention.

PMID- 17030592
TI  - Metastatic disease of the spine.
AB  - Metastatic spine disease accounts for 10% to 30% of new cancer diagnoses
      annually. The most frequent presentation is axial pain. A thorough spinal
      examination includes assessment of local tenderness, deformity, limitation of
      motion, and signs of nerve root or cord compression. Plain radiographs are
      obtained routinely; for a suspected or known malignancy, radionuclide studies are
      essential. Magnetic resonance imaging is more specific than bone scans. Computed
      tomography-guided biopsy is considered to be safe and accurate for evaluating
      spinal lesions. Treatment is multidisciplinary, and virtually all treatment is
      palliative. Management is guided by three key issues: neurologic compromise,
      spinal instability, and individual patient factors. Site-directed radiation, with
      or without chemotherapy, is the mainstay of treating painful lesions that are not
      impinging on neural elements. New data documenting the benefit of surgical
      decompression using improved techniques such as anterior approaches have
      amplified the role of the spine surgeon in the care of these patients.

PMID- 17030593
TI  - Rehabilitation of the rotator cuff: an evaluation-based approach.
AB  - Rotator cuff disease of the shoulder, a common condition, is often
      incapacitating. Whether nonsurgical or surgical, successful management of rotator
      cuff disease is dependent on appropriate rehabilitation. Numerous rehabilitation
      protocols for the management of rotator cuff disease are based primarily on
      anecdotal clinical observation. The available literature on shoulder
      rehabilitation, in conjunction with clinical observation that takes into
      consideration the underlying tissue quality and structural integrity of the
      rotator cuff, can be compiled into a set of rehabilitation guidelines. The four
      phases of rehabilitation begin with maintaining and protecting the repair in the
      immediate postoperative period, followed by progression from early passive range
      of motion through return to preoperative levels of function.

PMID- 17030594
TI  - Down syndrome in children: the role of the orthopaedic surgeon.
AB  - Down syndrome, the result of trisomy of chromosome 21, is one of the most common
      chromosomal abnormalities. Patients have a characteristic facial appearance,
      variable levels of intelligence and self-care skills, and a variety of associated
      medical conditions. Orthopaedic manifestations occur frequently; most are related
      to hypotonia, joint hypermobility, and ligamentous laxity. Atlanto-occipital and
      atlantoaxial hypermobility, as well as bony anomalies of the cervical spine, can
      produce atlanto-occipital and cervical instability. Methods of screening for this
      instability, particularly with regard to participation in sports, are a subject
      of controversy. Scoliosis, hip instability, slipped capital femoral epiphysis,
      patellar instability, and foot deformities are other musculoskeletal conditions
      found in patients with Down syndrome that can be challenging for the orthopaedic
      surgeon to treat.

PMID- 17030595
TI  - Impaction bone grafting for revision hip arthroplasty: biology and clinical
      applications.
AB  - Impaction bone grafting techniques are useful when the orthopaedic surgeon is
      faced with large cavitary acetabular defects or a large ectatic femoral
      metaphysis or diaphysis. Impaction bone grafting of the acetabulum involves
      packing of cavitary defects with compressed particulate graft, followed by
      insertion of either a cemented or cementless acetabular component. Impaction
      grafting of the femur involves retrograde filling of the femoral canal with
      impacted particulate graft, creating a neomedullary canal into which a cemented
      femoral stem can be placed. Use of the impaction allografting technique is
      appealing, especially in young patients, because of its potential to restore bone
      stock. The technically demanding nature of the procedure, the risk of
      complications, and the unknown long-term fate of the impacted allograft highlight
      the need for ongoing assessment of this technique for revision total hip
      arthroplasties.

PMID- 17030597
TI  - Characterization of immunodeficiency in a patient with growth hormone
      insensitivity secondary to a novel STAT5b gene mutation.
AB  - STAT5 proteins are components of the common growth hormone and interleukin 2
      family of cytokines' signaling pathway. Mutations in the STAT5b gene, described
      in 2 patients, lead to growth hormone insensitivity that resembles Laron
      syndrome. Clinical immunodeficiency was also present, although immunologic
      defects have not been well characterized thus far. Here we describe a 16-year-old
      girl who suffered generalized eczema and recurrent infections of the skin and
      respiratory tract since birth. She also suffered severe chronic lung disease and
      multiple episodes of herpetic keratitis. Clinical features of congenital growth
      hormone deficiency were observed, such as persistently low growth rate, severely
      delayed bone age, and postnatal growth failure resulting from growth hormone
      resistance. This combined phenotype of growth hormone insensitivity and
      immunodeficiency was attributable to a homozygous C-->T transition that resulted
      in a nonsense mutation at codon 152 in exon 5 of the STAT5b gene. This novel
      mutation determined a complete absence of protein expression. The main
      immunologic findings were moderate T-cell lymphopenia (1274/mm3), normal CD4/CD8
      ratio, and very low numbers of natural killer (18/mm3) and gammadelta T (5/mm3)
      cells. T cells presented a chronically hyperactivated phenotype. In vitro T-cell
      proliferation and interleukin 2 signaling were impaired. CD4+ and CD25+
      regulatory T cells were significantly diminished, and they probably contributed
      to the signs of homeostatic mechanism deregulation found in this patient. This
      new case, in accordance with 2 previously reported cases, definitely demonstrates
      the significant role of the STAT5b protein in mediating growth hormone actions.
      Furthermore, the main immunologic findings bring about an explanation for the
      clinical immunodeficiency features and reveal for the first time the relevant
      role of STAT5b as a key protein for T-cell functions in humans.

PMID- 17030598
TI  - Exposure to medical test irradiation and acute leukemia among children with Down
      syndrome: a report from the Children's Oncology Group.
AB  - OBJECTIVE: The etiology of acute childhood leukemia is not well understood,
      particularly among children with Down syndrome, in whom a 10- to 20-fold
      increased risk of leukemogenesis has been reported compared with children without
      Down syndrome. We explored the association between medical test irradiation, a
      postulated leukemogenic agent, and acute leukemia among children with Down
      syndrome. PATIENTS AND METHODS: Children with Down syndrome (controls) were
      frequency matched on age to children with Down syndrome and leukemia (cases)
      diagnosed at ages 0 to 19 years during the period 1997-2002 at participating
      Children's Oncology Group institutions in North America. Telephone interviews
      were completed with mothers of 158 cases (n = 97 acute lymphoblastic leukemia and
      n = 61 acute myeloid leukemia) and 173 controls. Paternal interviews were
      completed with 275 fathers and 40 mothers serving as surrogates. Three
      irradiation exposure periods were examined: preconception, in utero, and
      postnatal. Multivariate unconditional logistic regression models were constructed
      to evaluate the associations of interest, resulting in odds ratios and 95%
      confidence intervals. RESULTS: There was little evidence that maternal or
      paternal preconception irradiation exposure, intrauterine exposure, or postnatal
      exposure contributes to leukemogenesis in children with Down syndrome. Overall,
      no evidence for an effect of any periconceptional exposure was observed. Similar
      results were observed among acute lymphoblastic leukemia and acute myeloid
      leukemia cases analyzed separately. CONCLUSIONS: This was the first study, to our
      knowledge, to examine such an association among this unique patient population.
      The results do not provide evidence of a positive association between ionizing
      radiation exposure and acute leukemia among children with Down syndrome. The
      absence of an association should be encouraging for concerned parents of children
      with Down syndrome who undergo a series of diagnostic radiographs in the course
      of their standard care.

PMID- 17030599
TI  - Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report
      and literature review.
AB  - Digestive tract involvement in Langerhans cell histiocytosis is exceedingly rare.
      We report a case of Langerhans cell histiocytosis in an otherwise thriving
      neonate presenting with hematochezia, anemia, and rash. We also review the few
      cases of Langerhans cell histiocytosis with gastrointestinal involvement reported
      in the English-language medical literature. Although gastrointestinal involvement
      can range in severity from mild to life-threatening, its presence may be
      indicative of multisystemic disease, and aggressive treatment should be
      considered.

PMID- 17030600
TI  - The CDM superfamily protein MBC directs myoblast fusion through a mechanism that
      requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of
      direct interaction with DCrk.
AB  - Myoblast city (mbc), a member of the CDM superfamily, is essential in the
      Drosophila melanogaster embryo for fusion of myoblasts into multinucleate fibers.
      Using germ line clones in which both maternal and zygotic contributions were
      eliminated and rescue of the zygotic loss-of-function phenotype, we established
      that mbc is required in the fusion-competent subset of myoblasts. Along with its
      close orthologs Dock180 and CED-5, MBC has an SH3 domain at its N terminus,
      conserved internal domains termed DHR1 and DHR2 (or "Docker"), and C-terminal
      proline-rich domains that associate with the adapter protein DCrk. The importance
      of these domains has been evaluated by the ability of MBC mutations and deletions
      to rescue the mbc loss-of-function muscle phenotype. We demonstrate that the SH3
      and Docker domains are essential. Moreover, ethyl methanesulfonate-induced
      mutations that change amino acids within the MBC Docker domain to residues that
      are conserved in other CDM family members nevertheless eliminate MBC function in
      the embryo, which suggests that these sites may mediate interactions specific to
      Drosophila MBC. A functional requirement for the conserved DHR1 domain, which
      binds to phosphatidylinositol 3,4,5-triphosphate, implicates phosphoinositide
      signaling in myoblast fusion. Finally, the proline-rich C-terminal sites mediate
      strong interactions with DCrk, as expected. These sites are not required for MBC
      to rescue the muscle loss-of-function phenotype, however, which suggests that
      MBC's role in myoblast fusion can be carried out independently of direct DCrk
      binding.

PMID- 17030601
TI  - Smc5/6 is required for repair at collapsed replication forks.
AB  - In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins
      are found in conserved multisubunit protein complexes required for chromosomal
      organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion
      while two condensin complexes containing Smc2/4 facilitate chromosome
      condensation. Smc5/6 scaffolds an essential complex required for homologous
      recombination repair. We have examined the response of smc6 mutants to the
      inhibition of DNA replication. We define homologous recombination-dependent and 
      independent functions for Smc6 during replication inhibition and provide evidence
      for a Rad60-independent function within S phase, in addition to a Rad60-dependent
      function following S phase. Both genetic and physical data show that when forks
      collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required
      for the effective repair of resulting lesions but not for the recruitment of
      recombination proteins. We further demonstrate that when the Rad60-dependent,
      post-S-phase Smc6 function is compromised, the resulting recombination-dependent
      DNA intermediates that accumulate following release from replication arrest are
      not recognized by the G2/M checkpoint.

PMID- 17030602
TI  - Cell confluence regulates hepatocyte growth factor-stimulated cell morphogenesis
      in a beta-catenin-dependent manner.
AB  - Following organ injury, morphogenic epithelial responses can vary depending on
      local cell density. In the present study, the role of cell confluence in
      determining the responsiveness of renal epithelial cells to the dedifferentiating
      morphogenic signals of hepatocyte growth factor (HGF) was examined. Increasing
      confluence resulted in a greater tendency of cells to organize into epithelial
      tubes and a significant decrease in migratory responsiveness to HGF. Analysis of
      downstream signaling revealed that the HGF receptor c-Met was equally activated
      in confluent and nonconfluent cells following HGF stimulation but that
      phosphoinositide 3-kinase-dependent activation of Akt and Rac were selectively
      diminished in confluent cells. In nonconfluent cells treated with HGF, the high
      level of Akt activation resulted in inhibitory phosphorylation of glycogen
      synthase kinase 3beta (GSK-3beta) and increased beta-catenin nuclear signaling.
      In contrast, confluent cells, in which HGF-stimulated Akt activation was
      diminished, displayed less inhibitory phosphorylation of GSK-3beta and less
      nuclear signaling by beta-catenin. Overexpression of beta-catenin (SA), which
      cannot be phosphorylated by GSK-3beta and targeted for ubiquitination,
      significantly increased migration in fully confluent cells. Thus, cells
      maintained at high confluence selectively downregulate signaling events such as
      Rac activation and beta-catenin-dependent transcription that would otherwise
      promote cell dedifferentiation and migration.

PMID- 17030603
TI  - The Drosophila histone acetyltransferase Gcn5 and transcriptional adaptor Ada2a
      are involved in nucleosomal histone H4 acetylation.
AB  - The histone acetyltransferase (HAT) Gcn5 plays a role in chromatin structure and
      gene expression regulation as a catalytic component of multiprotein complexes,
      some of which also contain Ada2-type transcriptional coactivators. Data obtained
      mostly from studies on yeast (Saccharomyces cerevisiae) suggest that Ada2
      potentiates Gcn5 activity and substrate recognition. dAda2b, one of two related
      Ada2 proteins of Drosophila melanogaster, was recently found to play a role in
      complexes acetylating histone 3 (H3). Evidence of an in vivo functional link
      between the related coactivator dAda2a and dGcn5, however, is lacking. Here we
      present data on the genetic interaction of dGcn5 and dAda2a. The loss of either
      dGcn5 or dAda2a function results in similar chromosome structural and
      developmental defects. In dAda2a mutants, the nucleosomal H4 acetylation at
      lysines 12 and 5 is significantly reduced, while the acetylation established by
      dAda2b-containing Gcn5 complexes at H3 lysines 9 and 14 is unaffected. The data
      presented here, together with our earlier data on the function of dAda2b, provide
      evidence that related Ada2 proteins of Drosophila, together with Gcn5 HAT, are
      involved in the acetylation of specific lysine residues in the N-terminal tails
      of nucleosomal H3 and H4. Our data suggest dAda2a involvement in both uniformly
      distributed H4 acetylation and gene-specific transcription regulation.

PMID- 17030604
TI  - Evidence that the transcription elongation function of Rpb9 is involved in
      transcription-coupled DNA repair in Saccharomyces cerevisiae.
AB  - Rpb9, a small nonessential subunit of RNA polymerase II, has been shown to have
      multiple transcription-related functions in Saccharomyces cerevisiae. These
      functions include promoting transcription elongation and mediating a subpathway
      of transcription-coupled repair (TCR) that is independent of Rad26, the homologue
      of human Cockayne syndrome complementation group B protein. Rpb9 is composed of
      three distinct domains: the N-terminal Zn1, the C-terminal Zn2, and the central
      linker. Here we show that the Zn1 and linker domains are essential, whereas the
      Zn2 domain is almost dispensable, for both transcription elongation and TCR
      functions. Impairment of transcription elongation, which does not dramatically
      compromise Rad26-mediated TCR, completely abolishes Rpb9-mediated TCR.
      Furthermore, Rpb9 appears to be dispensable for TCR if its transcription
      elongation function is compensated for by removing a transcription
      repression/elongation factor. Our data suggest that the transcription elongation
      function of Rpb9 is involved in TCR.

PMID- 17030605
TI  - Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor
      metastasis.
AB  - The insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that
      organize signaling complexes downstream of activated cell surface receptors.
      Here, we show that IRS-1 and IRS-2, despite significant homology, play critical
      yet distinct functions in breast cancer, and we identify specific signaling
      pathways that are influenced by IRS-1 using the polyoma virus middle-T (PyV-MT)
      transgenic mouse model of mammary carcinoma and Irs-1 null (Irs1(-/-)) mice. The
      absence of Irs-1 expression enhanced metastatic spread significantly without a
      significant effect on primary tumor growth. Orthotopic transplant studies
      revealed that the increased metastatic potential of Irs1-deficient tumor cells is
      cell autonomous. Mammary tumors that developed in PyV-MT::Irs1(-/-) mice
      exhibited elevated Irs-2 function and enhanced phosphatidylinositol 3
      kinase/Akt/mTor activity, suggesting that one mechanism by which Irs-1 impedes
      metastasis is to suppress Irs-2-dependent signaling. In support of this
      mechanism, reduction of Irs-2 expression in Irs1(-/-) tumor cells restored mTor
      signaling to wild-type levels. PyV-MT::Irs1(-/-) tumors also exhibited a
      significant increase in vascular endothelial growth factor expression and
      microvessel density, which could facilitate their dissemination. The significance
      of our findings for human breast cancer is heightened by our observation that Irs
      1 is inactivated in wild-type, metastatic mammary tumors by serine
      phosphorylation. Collectively, our findings reveal that inactivation of IRS-1
      enhances breast cancer metastasis and support the novel hypothesis that IRS-1 has
      metastasis suppressor functions for breast cancer.

PMID- 17030606
TI  - The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3
      cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization
      of p38 MAPK.
AB  - MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein
      kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired
      inflammatory response although MK3, which displays extensive structural
      similarities and identical functional properties in vitro, is still present.
      Here, we analyze tumor necrosis factor (TNF) production and expression of p38
      MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there
      are no significant differences with wild-type animals. We show that in vivo MK2
      and MK3 are expressed and activated in parallel. However, the level of activity
      of MK2 is always significantly higher than that of MK3. Accordingly, we
      hypothesized that MK3 could have significant effects only in an MK2-free
      background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice
      are viable and show no obvious defects due to loss of compensation between MK2
      and MK3. However, there is a further reduction of TNF production and expression
      of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This
      finding, together with the observation that ectopically expressed MK3 can rescue
      MK2 deficiency similarly to MK2, indicates that both kinases share the same
      physiological function in vivo but are expressed to different levels.

PMID- 17030607
TI  - The rad51-K191R ATPase-defective mutant is impaired for presynaptic filament
      formation.
AB  - The nucleoprotein filament formed by Rad51 polymerization on single-stranded DNA
      is essential for homologous pairing and strand exchange. ATP binding is required
      for Rad51 nucleoprotein filament formation and strand exchange, but ATP
      hydrolysis is not required for these functions in vitro. Previous studies have
      shown that a yeast strain expressing the rad51-K191R allele is sensitive to
      ionizing radiation, suggesting an important role for ATP hydrolysis in vivo. The
      recruitment of Rad51-K191R to double-strand breaks is defective in vivo, and this
      phenotype can be suppressed by elimination of the Srs2 helicase, an antagonist of
      Rad51 filament formation. The phenotype of the rad51-K191R strain is also
      suppressed by overexpression of Rad54. In vitro, the Rad51-K191R protein exhibits
      a slight decrease in binding to DNA, consistent with the defect in presynaptic
      filament formation. However, the rad51-K191R mutation is dominant in heterozygous
      diploids, indicating that the defect is not due simply to reduced affinity for
      DNA. We suggest the Rad51-K191R protein either forms an altered filament or is
      defective in turnover, resulting in a reduced pool of free protein available for
      DNA binding.

PMID- 17030608
TI  - BRF1 protein turnover and mRNA decay activity are regulated by protein kinase B
      at the same phosphorylation sites.
AB  - BRF1 posttranscriptionally regulates mRNA levels by targeting ARE-bearing
      transcripts to the decay machinery. We previously showed that protein kinase B
      (PKB) phosphorylates BRF1 at Ser92, resulting in binding to 14-3-3 and impairment
      of mRNA decay activity. Here we identify an additional regulatory site at Ser203
      that cooperates in vivo with Ser92. In vitro kinase labeling and wortmannin
      sensitivity indicate that Ser203 phosphorylation is also performed by PKB.
      Mutation of both serines to alanine uncouples BRF1 from PKB regulation, leading
      to constitutive mRNA decay even in the presence of stabilizing signals. BRF1
      protein is labile because of proteasomal degradation (half-life, <3 h) but
      becomes stabilized upon phosphorylation and is less stable in PKBalpha(-/-)
      cells. Surprisingly, phosphorylation-dependent protein stability is also
      regulated by Ser92 and Ser203, with parallel phosphorylation required at these
      sites. Phosphorylation-dependent binding to 14-3-3 is abolished only when both
      sites are mutated. Cell compartment fractionation experiments support a model in
      which binding to 14-3-3 sequesters BRF1 through relocalization and prevents it
      from executing its mRNA decay activity, as well as from proteasomal degradation,
      thereby maintaining high BRF1 protein levels that are required to reinstate decay
      upon dissipation of the stabilizing signal.

PMID- 17030609
TI  - Complex formation with Rev1 enhances the proficiency of Saccharomyces cerevisiae
      DNA polymerase zeta for mismatch extension and for extension opposite from DNA
      lesions.
AB  - Rev1, a Y family DNA polymerase (Pol) functions together with Polzeta, a B family
      Pol comprised of the Rev3 catalytic subunit and Rev7 accessory subunit, in
      promoting translesion DNA synthesis (TLS). Extensive genetic studies with
      Saccharomyces cerevisiae have indicated a requirement of both Polzeta and Rev1
      for damage-induced mutagenesis, implicating their involvement in mutagenic TLS.
      Polzeta is specifically adapted to promote the extension step of lesion bypass,
      as it proficiently extends primer termini opposite DNA lesions, and it is also a
      proficient extender of mismatched primer termini on undamaged DNAs. Since TLS
      through UV-induced lesions and various other DNA lesions does not depend upon the
      DNA-synthetic activity of Rev1, Rev1 must contribute to Polzeta-dependent TLS in
      a nonenzymatic way. Here, we provide evidence for the physical association of
      Rev1 with Polzeta and show that this binding is mediated through the C terminus
      of Rev1 and the polymerase domain of Rev3. Importantly, a rev1 mutant that lacks
      the C-terminal 72 residues which inactivate interaction with Rev3 exhibits the
      same high degree of UV sensitivity and defectiveness in UV-induced mutagenesis as
      that conferred by the rev1Delta mutation. We propose that Rev1 binding to Polzeta
      is indispensable for the targeting of Polzeta to the replication fork stalled at
      a DNA lesion. In addition to this structural role, Rev1 binding enhances the
      proficiency of Polzeta for the extension of mismatched primer termini on
      undamaged DNAs and for the extension of primer termini opposite DNA lesions.

PMID- 17030610
TI  - Differential recruitment of methylated CpG binding domains by the orphan receptor
      GCNF initiates the repression and silencing of Oct4 expression.
AB  - The pluripotent factor Oct4 is a key transcription factor that maintains
      embryonic stem (ES) cell self-renewal and is down-regulated upon the
      differentiation of ES cells and silenced in somatic cells. A combination of cis
      elements, transcription factors, and epigenetic modifications, such as DNA
      methylation, are involved in the regulation of Oct4 gene expression. Here we show
      that the orphan nuclear receptor GCNF initiates Oct4 repression and DNA
      methylation by the differential recruitment of MBD (methylated CpG binding
      domain) factors to the promoter. Compared with wild-type ES cells and
      gastrulating embryos, Oct4 repression is lost and its proximal promoter is
      significantly hypomethylated in RA-differentiated GCNF(-/-) ES cells. The Oct4
      gene is reexpressed in some somatic cells of GCNF(-/-) embryos, showing that it
      has not been properly silenced coincident with reduced DNA methylation of its
      promoter. Efforts to characterize mediators of GCNF's repressive function and DNA
      methylation of the Oct4 promoter identified methyl-DNA binding proteins, MBD3 and
      MBD2, as GCNF-interacting factors. In P19 and ES cells, upon differentiation,
      endogenous GCNF binds to the Oct4 proximal promoter and differentially recruits
      MBD3 and MBD2. In differentiated GCNF(-/-) ES cells, recruitment of MBD3 and MBD2
      to the Oct4 promoter is lost, and repression of Oct4 expression and DNA
      methylation fails to occur. RNA interference-mediated knockdown of MBD3 and/or
      MBD2 expression results in reduced Oct4 repression in differentiated P19 and ES
      cells. Repression of Oct4 expression and recruitment of MBD3 are maintained in de
      novo DNA methylation-deficient ES cells (Dnmt3A/3B-null cells), while MBD2
      recruitment is lost. Thus, recruitment of MBD3 and MBD2 by GCNF links two events,
      gene-specific repression and DNA methylation, which occur differentially at the
      Oct4 promoter. GCNF initiates the repression and epigenetic modification of Oct4
      gene during ES cell differentiation.

PMID- 17030611
TI  - Autophagy is activated for cell survival after endoplasmic reticulum stress.
AB  - Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic
      reticulum (ER) by the unfolded protein response, involving the induction of
      molecular chaperones, translational attenuation, and ER-associated degradation,
      to prevent cell death. Here, we found that the autophagy system is activated as a
      novel signaling pathway in response to ER stress. Treatment of SK-N-SH
      neuroblastoma cells with ER stressors markedly induced the formation of
      autophagosomes, which were recognized at the ultrastructural level. The formation
      of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"),
      representing autophagosomes, was extensively induced in cells exposed to ER
      stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells
      treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER
      stress was inhibited, indicating that the IRE1-JNK pathway is required for
      autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6
      knockdown cells showed that autophagy was induced after ER stress in a manner
      similar to the wild-type cells. Disturbance of autophagy rendered cells
      vulnerable to ER stress, suggesting that autophagy plays important roles in cell
      survival after ER stress.

PMID- 17030612
TI  - Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting
      complex/cyclosome in budding yeast.
AB  - Cdh1 is a coactivator of the anaphase-promoting complex/cyclosome (APC/C) and
      contributes to mitotic exit and G1 maintenance by facilitating the
      polyubiquitination and subsequent proteolysis of specific substrates. Here, we
      report that budding yeast Cdh1 is a component of a cell cycle-regulated complex
      that includes the 14-3-3 homologs Bmh1 and Bmh2 and a previously uncharacterized
      protein, which we name Acm1 (APC/CCdh1 modulator 1). Association of Cdh1 with
      Bmh1 and Bmh2 requires Acm1, and the Acm1 protein is cell cycle regulated,
      appearing late in G1 and disappearing in late M. In acm1Delta strains, Cdh1
      localization to the bud neck and association with two substrates, Clb2 and Hsl1,
      were strongly enhanced. Several lines of evidence suggest that Acm1 can suppress
      APC/CCdh1-mediated proteolysis of mitotic cyclins. First, overexpression of Acm1
      fully restored viability to cells expressing toxic levels of Cdh1 or a
      constitutively active Cdh1 mutant lacking inhibitory phosphorylation sites.
      Second, overexpression of Acm1 was toxic in sic1Delta cells. Third, ACM1 deletion
      exacerbated a low-penetrance elongated-bud phenotype caused by modest
      overexpression of Cdh1. This bud elongation was independent of the morphogenesis
      checkpoint, and the combination of acm1Delta and hsl1Delta resulted in a dramatic
      enhancement of bud elongation and G2/M delay. Effects on bud elongation were
      attenuated when Cdh1 was replaced with a mutant lacking the C-terminal IR
      dipeptide, suggesting that APC/C-dependent proteolysis is required for this
      phenotype. We propose that Acm1 and Bmh1/Bmh2 constitute a specialized inhibitor
      of APC/CCdh1.

PMID- 17030613
TI  - Perk-dependent translational regulation promotes tumor cell adaptation and
      angiogenesis in response to hypoxic stress.
AB  - It has been well established that the tumor microenvironment can promote tumor
      cell adaptation and survival. However, the mechanisms that influence malignant
      progression have not been clearly elucidated. We have previously demonstrated
      that cells cultured under hypoxic/anoxic conditions and transformed cells in
      hypoxic areas of tumors activate a translational control program known as the
      integrated stress response (ISR). Here, we show that tumors derived from K-Ras
      transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller and exhibit
      less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a
      tumor microenvironment that favors the formation of functional microvessels.
      These observations were corroborated by a microarray analysis of polysome-bound
      RNA in aerobic and hypoxic Perk(+/+) and Perk(-/-) MEFs. This analysis revealed
      that a subset of proangiogenic transcripts is preferentially translated in a Perk
      dependent manner; these transcripts include VCIP, an adhesion molecule that
      promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken
      with the concomitant Perk-dependent translational induction of additional
      proangiogenic genes identified by our microarray analysis, this study suggests
      that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating
      the translation of angiogenic factors necessary for the development of functional
      microvessels and further supports the contention that the Perk pathway could be
      an attractive target for novel antitumor modalities.

PMID- 17030614
TI  - Profile of histone lysine methylation across transcribed mammalian chromatin.
AB  - Complex patterns of histone lysine methylation encode distinct functions within
      chromatin. We previously reported that trimethylation of lysine 9 of histone H3
      (H3K9) occurs at both silent heterochromatin and at the transcribed regions of
      active mammalian genes, suggesting that the extent of histone lysine methylation
      involved in mammalian gene activation is not completely defined. To identify
      additional sites of histone methylation that respond to mammalian gene activity,
      we describe here a comparative assessment of all six known positions of histone
      lysine methylation and relate them to gene transcription. Using several model
      loci, we observed high trimethylation of H3K4, H3K9, H3K36, and H3K79 in the
      transcribed region, consistent with previous findings. We identify H4K20
      monomethylation, a modification previously linked with repression, as a mark of
      transcription elongation in mammalian cells. In contrast, H3K27 monomethylation,
      a modification enriched at pericentromeric heterochromatin, was observed broadly
      distributed throughout all euchromatic sites analyzed, with selective depletion
      in the vicinity of the transcription start sites at active genes. Together, these
      results underscore that similar to other described methyl-lysine modifications,
      H4K20 and H3K27 monomethylation are versatile and dynamic with respect to gene
      activity, suggesting the existence of novel site-specific methyltransferases and
      demethylases coupled to the transcription cycle.

PMID- 17030615
TI  - The DEK nuclear autoantigen is a secreted chemotactic factor.
AB  - The nuclear DNA-binding protein DEK is an autoantigen that has been implicated in
      the regulation of transcription, chromatin architecture, and mRNA processing. We
      demonstrate here that DEK is actively secreted by macrophages and is also found
      in synovial fluid samples from patients with juvenile arthritis. Secretion of DEK
      is modulated by casein kinase 2, stimulated by interleukin-8, and inhibited by
      dexamethasone and cyclosporine A, consistent with a role as a proinflammatory
      molecule. DEK is secreted in both a free form and in exosomes, vesicular
      structures in which transcription-modulating factors such as DEK have not
      previously been found. Furthermore, DEK functions as a chemotactic factor,
      attracting neutrophils, CD8+ T lymphocytes, and natural killer cells. Therefore,
      the DEK autoantigen, previously described as a strictly nuclear protein, is
      secreted and can act as an extracellular chemoattractant, suggesting a direct
      role for DEK in inflammation.

PMID- 17030616
TI  - HSP70 induction by ING proteins sensitizes cells to tumor necrosis factor alpha
      receptor-mediated apoptosis.
AB  - ING proteins affect apoptosis, growth, and DNA repair by transducing stress
      signals such as DNA damage, binding histones, and subsequently regulating
      chromatin structure and p53 activity. p53 target genes, including the p21 cyclin
      dependent kinase inhibitor and Bax, an inducer of apoptosis, are regulated by ING
      proteins. To identify additional targets downstream of p33ING1 and p32ING2, cDNA
      microarrays were performed on phenotypically normal human primary fibroblasts.
      The 0.36% of genes affected by ING proteins in primary fibroblasts were distinct
      from targets seen in established cells and included the HSP70 heat shock gene,
      whose promoter was specifically induced >10-fold. ING1-induced expression of
      HSP70 shifted cells from survival to a death pathway in response to tumor
      necrosis factor alpha (TNF-alpha), and p33ING1b protein showed synergy with TNF
      alpha in inducing apoptosis, which correlated with reduced NF-kappaB-dependent
      transcription. These findings are consistent with previous reports that HSP70
      promotes TNF-alpha-mediated apoptosis by binding I-kappaBeta kinase gamma and
      impairing NF-kappaB survival signaling. Induction of HSP70 required the amino
      terminus of ING1b but not the plant homeodomain region that was recently
      identified as a histone binding domain. Regulation of HSP70 gene expression by
      the ING tumor suppressors provides a novel link between the INGs and the stress
      regulated NF-kappaB survival pathway important in hypoxia and angiogenesis.

PMID- 17030617
TI  - Cripto binds transforming growth factor beta (TGF-beta) and inhibits TGF-beta
      signaling.
AB  - Cripto is a developmental oncoprotein and a member of the epidermal growth factor
      Cripto, FRL-1, Cryptic family of extracellular signaling molecules. In addition
      to having essential functions during embryogenesis, Cripto is highly expressed in
      tumors and promotes tumorigenesis. During development, Cripto acts as an obligate
      coreceptor for transforming growth factor beta (TGF-beta) ligands, including
      nodals, growth and differentiation factor 1 (GDF1), and GDF3. As an oncogene,
      Cripto is thought to promote tumor growth via mechanisms including activation of
      mitogenic signaling pathways and antagonism of activin signaling. Here, we
      provide evidence supporting a novel mechanism in which Cripto inhibits the tumor
      suppressor function of TGF-beta. Cripto bound TGF-beta and reduced the
      association of TGF-beta with its type I receptor, TbetaRI. Consistent with its
      ability to block receptor assembly, Cripto suppressed TGF-beta signaling in
      multiple cell types and diminished the cytostatic effects of TGF-beta in mammary
      epithelial cells. Furthermore, targeted disruption of Cripto expression by use of
      small inhibitory RNA enhanced TGF-beta signaling, indicating that endogenous
      Cripto plays a role in restraining TGF-beta responses.

PMID- 17030618
TI  - Timing and sequence requirements defined for embryonic maintenance of imprinted
      DNA methylation at Rasgrf1.
AB  - Epigenetic programming is critical for normal development of mammalian embryos.
      Errors cause misexpression of genes and aberrant development (E. Li, C. Beard,
      and R. Jaenisch, Nature 366:362-365, 1993). Imprinted genes are important targets
      of epigenetic regulation, but little is known about how the epigenetic patterns
      are established in the parental germ lines and maintained in the embryo. Paternal
      allele-specific expression at the imprinted Rasgrf1 locus in mice is controlled
      by paternal allele-specific methylation at a differentially methylated domain
      (DMD). DMD methylation is in turn controlled by a direct repeat sequence
      immediately downstream of the DMD which is required for establishing Rasgrf1
      methylation in the male germ line (B. J. Yoon et al., Nat. Genet. 30:92-96,
      2002). To determine if these repeats have a role in methylation maintenance, we
      developed a conditional deletion of the repeat sequence in mice and showed that
      the repeats are also required during a narrow interval to maintain paternal
      methylation of Rasgrf1 in developing embryos. Removing the repeats upon
      fertilization caused a total loss of methylation by the morula stage, but by the
      epiblast stage, the repeats were completely dispensable for methylation
      maintenance. This developmental interval coincides with genome-wide demethylation
      and remethylation in mice which most imprinted genes resist. Our data show that
      the Rasgrf1 repeats serve at least two functions: first, to establish Rasgrf1 DNA
      methylation in the male germ line, and second, to resist global demethylation in
      the preimplantation embryo.

PMID- 17030620
TI  - Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of
      stabilized transcripts in TTP-deficient fibroblasts.
AB  - Tristetraprolin (TTP) is a tandem CCCH zinc finger protein that was identified
      through its rapid induction by mitogens in fibroblasts. Studies of TTP-deficient
      mice and cells derived from them showed that TTP could bind to certain AU-rich
      elements in mRNAs, leading to increases in the rates of mRNA deadenylation and
      destruction. Known physiological target mRNAs for TTP include tumor necrosis
      factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin
      2beta. Here we used microarray analysis of RNA from wild-type and TTP-deficient
      fibroblast cell lines to identify transcripts with different decay rates, after
      serum stimulation and actinomycin D treatment. Of 250 mRNAs apparently stabilized
      in the absence of TTP, 23 contained two or more conserved TTP binding sites; nine
      of these appeared to be stabilized on Northern blots. The most dramatically
      affected transcript encoded the protein Ier3, recently implicated in the
      physiological control of blood pressure. The Ier3 transcript contained several
      conserved TTP binding sites that could bind TTP directly and conferred TTP
      sensitivity to the mRNA in cell transfection studies. These studies have
      identified several new, physiologically relevant TTP target transcripts in
      fibroblasts; these target mRNAs encode proteins from a variety of functional
      classes.

PMID- 17030619
TI  - Essential role of phospholipase C gamma 2 in early B-cell development and Myc
      mediated lymphomagenesis.
AB  - Phospholipase Cgamma2 (PLCgamma2) is a critical signaling effector of the B-cell
      receptor (BCR). Here we show that PLCgamma2 deficiency impedes early B-cell
      development, resulting in an increase of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large
      pre-B cells. PLCgamma2 deficiency impairs pre-BCR-mediated functions, leading to
      enhanced interleukin-7 (IL-7) signaling and elevated levels of RAGs in the
      selected large pre-B cells. Consequently, PLCgamma2 deficiency renders large pre
      B cells susceptible to transformation, resulting in dramatic acceleration of Myc
      induced lymphomagenesis. PLCgamma2(-/-) Emu-Myc transgenic mice mainly develop
      lymphomas of B220+ CD43+ BP-1+ CD24hi pre-BCR+ large pre-B-cell origin, which are
      uncommon in wild-type Emu-Myc transgenics. Furthermore, lymphomas from PLCgamma2(
      /-) Emu-Myc transgenic mice exhibited a loss of p27Kip1 and often displayed
      alterations in Arf or p53. Thus, PLCgamma2 plays an important role in pre-BCR
      mediated early B-cell development, and its deficiency leads to markedly increased
      pools of the most at-risk large pre-B cells, which display hyperresponsiveness to
      IL-7 and express high levels of RAGs, making them prone to secondary mutations
      and Myc-induced malignancy.

PMID- 17030621
TI  - Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity.
AB  - The receptor tyrosine kinase ErbB2 plays a crucial role in tumorigenesis. We
      showed previously that the molecular chaperone Hsp90 protects ErbB2 from
      proteasome-mediated degradation by binding to a short loop structure in the N
      lobe of the kinase domain. Here we show that loss of Hsp90 binding correlates
      with enhanced ErbB2 kinase activity and its transactivating potential,
      concomitant with constitutively increased phosphorylation of Tyr877, located in
      the activation loop of the kinase domain. We show further that Tyr877
      phosphorylation is mediated by Src and that it is necessary for the enhanced
      kinase activity of ErbB2. Finally, computer modeling of the kinase domain
      suggests a phosphorylation-dependent reorientation of the activation loop,
      denoting the importance of Tyr877 phosphorylation for ErbB2 activity. These
      findings suggest that Hsp90 binding to ErbB2 participates in regulation of kinase
      activity as well as kinase stability.

PMID- 17030622
TI  - Cbln1 is essential for interaction-dependent secretion of Cbln3.
AB  - Cbln1 and the orphan glutamate receptor GluRdelta2 are pre- and postsynaptic
      components, respectively, of a novel transneuronal signaling pathway regulating
      synapse structure and function. We show here that Cbln1 is secreted from
      cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1
      and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice
      have deficits identical to those of cbln1 knockout mice. The basis for these
      discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's
      degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3,
      whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in
      Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only
      when bound to Cbln1. Structural modeling and mutation analysis reveal that, by
      constituting a steric clash that is masked upon binding Cbln1 in a "hide-and-run"
      mechanism of endoplasmic reticulum retention, a single arginine confers the
      unique properties of Cbln3.

PMID- 17030623
TI  - Imp associates with squid and Hrp48 and contributes to localized expression of
      gurken in the oocyte.
AB  - Localization and translational control of Drosophila melanogaster gurken and
      oskar mRNAs rely on the hnRNP proteins Squid and Hrp48, which are complexed with
      one another in the ovary. Imp, the Drosophila homolog of proteins acting in
      localization of mRNAs in other species, is also associated with Squid and Hrp48.
      Notably, Imp is concentrated at sites of gurken and oskar mRNA localization in
      the oocyte, and alteration of gurken localization also alters Imp distribution.
      Imp binds gurken mRNA with high affinity in vitro; thus, the colocalization with
      gurken mRNA in vivo is likely to be the result of direct binding. Imp mutants
      support apparently normal regulation of gurken and oskar mRNAs. However, loss of
      Imp activity partially suppresses a gurken misexpression phenotype, indicating
      that Imp does act in control of gurken expression but has a largely redundant
      role that is only revealed when normal gurken expression is perturbed.
      Overexpression of Imp disrupts localization of gurken mRNA as well as
      localization and translational regulation of oskar mRNA. The opposing effects of
      reduced and elevated Imp activity on gurken mRNA expression indicate a role in
      gurken mRNA regulation.

PMID- 17030625
TI  - AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1
      mRNA stability.
AB  - DNA methylation is a major determinant of epigenetic inheritance. DNA
      methyltransferase 1 (DNMT1) is the enzyme responsible for the maintenance of DNA
      methylation patterns during cell division, and deregulated expression of DNMT1
      leads to cellular transformation. We show herein that AU-rich element/poly(U)
      binding/degradation factor 1 (AUF1)/heterogeneous nuclear ribonucleoprotein D
      interacts with an AU-rich conserved element in the 3' untranslated region of the
      DNMT1 mRNA and targets it for destabilization by the exosome. AUF1 protein levels
      are regulated by the cell cycle by the proteasome, resulting in cell cycle
      specific destabilization of DNMT1 mRNA. AUF1 knock down leads to increased DNMT1
      expression and modifications of cell cycle kinetics, increased DNA
      methyltransferase activity, and genome hypermethylation. Concurrent AUF1 and
      DNMT1 knock down abolishes this effect, suggesting that the effects of AUF1 knock
      down on the cell cycle are mediated at least in part by DNMT1. In this study, we
      demonstrate a link between AUF1, the RNA degradation machinery, and maintenance
      of the epigenetic integrity of the cell.

PMID- 17030624
TI  - ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in
      response to DNA damage.
AB  - Alternative pre-mRNA splicing is a major mechanism utilized by eukaryotic
      organisms to expand their protein-coding capacity. To examine the role of cell
      signaling in regulating alternative splicing, we analyzed the splicing of the
      Drosophila melanogaster TAF1 pre-mRNA. TAF1 encodes a subunit of TFIID, which is
      broadly required for RNA polymerase II transcription. We demonstrate that TAF1
      alternative splicing generates four mRNAs, TAF1-1, TAF1-2, TAF1-3, and TAF1-4, of
      which TAF1-2 and TAF1-4 encode proteins that directly bind DNA through AT hooks.
      TAF1 alternative splicing was regulated in a tissue-specific manner and in
      response to DNA damage induced by ionizing radiation or camptothecin.
      Pharmacological inhibitors and RNA interference were used to demonstrate that
      ionizing-radiation-induced upregulation of TAF1-3 and TAF1-4 splicing in S2 cells
      was mediated by the ATM (ataxia-telangiectasia mutated) DNA damage response
      kinase and checkpoint kinase 2 (CHK2), a known ATM substrate. Similarly,
      camptothecin-induced upregulation of TAF1-3 and TAF1-4 splicing was mediated by
      ATR (ATM-RAD3 related) and CHK1. These findings suggest that inducible TAF1
      alternative splicing is a mechanism to regulate transcription in response to
      developmental or DNA damage signals and provide the first evidence that the
      ATM/CHK2 and ATR/CHK1 signaling pathways control gene expression by regulating
      alternative splicing.

PMID- 17030626
TI  - A putative Arabidopsis nucleoporin, AtNUP160, is critical for RNA export and
      required for plant tolerance to cold stress.
AB  - To study the genetic control of plant responses to cold stress, Arabidopsis
      thaliana mutants were isolated by a screen for mutations that impair cold-induced
      transcription of the CBF3-LUC reporter gene. We report here the characterization
      and cloning of a mutated gene, atnup160-1, which causes reduced CBF3-LUC
      induction under cold stress. atnup160-1 mutant plants display altered cold
      responsive gene expression and are sensitive to chilling stress and defective in
      acquired freezing tolerance. AtNUP160 was isolated through positional cloning and
      shown to encode a putative homolog of the animal nucleoporin Nup160. In addition
      to the impaired expression of CBF genes, microarray analysis revealed that a
      number of other genes important for plant cold tolerance were also affected in
      the mutants. The atnup160 mutants flower early and show retarded seedling growth,
      especially at low temperatures. AtNUP160 protein is localized at the nuclear rim,
      and poly(A)-mRNA in situ hybridization shows that mRNA export is defective in the
      atnup160-1 mutant plants. Our study suggests that Arabidopsis AtNUP160 is
      critical for the nucleocytoplasmic transport of mRNAs and that it plays important
      roles in plant growth and flowering time regulation and is required for cold
      stress tolerance.

PMID- 17030627
TI  - Neuromedin U receptor 2-deficient mice display differential responses in sensory
      perception, stress, and feeding.
AB  - Neuromedin U (NMU) is a highly conserved neuropeptide with a variety of
      physiological functions mediated by two receptors, peripheral NMUR1 and central
      nervous system NMUR2. Here we report the generation and phenotypic
      characterization of mice deficient in the central nervous system receptor NMUR2.
      We show that behavioral effects, such as suppression of food intake, enhanced
      pain response, and excessive grooming induced by intracerebroventricular NMU
      administration were abolished in the NMUR2 knockout (KO) mice, establishing a
      causal role for NMUR2 in mediating NMU's central effects on these behaviors. In
      contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with
      regard to stress, anxiety, body weight regulation, and food consumption. However,
      the NMUR2 KO mice showed reduced pain sensitivity in both the hot plate and
      formalin tests. Furthermore, facilitated excitatory synaptic transmission in
      spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not
      occur in NMUR2 KO mice. These results provide significant insights into a
      functional dissection of the differential contribution of peripherally or
      centrally acting NMU system. They suggest that NMUR2 plays a more significant
      role in central pain processing than other brain functions including
      stress/anxiety and regulation of feeding.

PMID- 17030628
TI  - Bone morphogenetic protein-induced MSX1 and MSX2 inhibit myocardin-dependent
      smooth muscle gene transcription.
AB  - During the onset and progression of atherosclerosis, the vascular smooth muscle
      cell (VSMC) phenotype changes from differentiated to dedifferentiated, and in
      some cases, this change is accompanied by osteogenic transition, resulting in
      vascular calcification. One characteristic of dedifferentiated VSMCs is the down
      regulation of smooth muscle cell (SMC) marker gene expression. Bone morphogenetic
      proteins (BMPs), which are involved in the induction of osteogenic gene
      expression, are detected in calcified vasculature. In this study, we found that
      the BMP2-, BMP4-, and BMP6-induced expression of Msx transcription factors (Msx1
      and Msx2) preceded the down-regulation of SMC marker expression in cultured
      differentiated VSMCs. Either Msx1 or Msx2 markedly reduced the myocardin
      dependent promoter activities of SMC marker genes (SM22alpha and caldesmon). We
      further investigated interactions between Msx1 and myocardin/serum response
      factor (SRF)/CArG-box motif (cis element for SRF) using coimmunoprecipitation,
      gel-shift, and chromatin immunoprecipitation assays. Our results showed that Msx1
      or Msx2 formed a ternary complex with SRF and myocardin and inhibited the binding
      of SRF or SRF/myocardin to the CArG-box motif, resulting in inhibition of their
      transcription.

PMID- 17030629
TI  - Increased susceptibility to isoproterenol-induced cardiac hypertrophy and
      impaired weight gain in mice lacking the histidine-rich calcium-binding protein.
AB  - The sarcoplasmic reticulum (SR) plays a critical role in excitation-contraction
      coupling by regulating the cytoplasmic calcium concentration of striated muscle.
      The histidine-rich calcium-binding protein (HRCBP) is expressed in the junctional
      SR, the site of calcium release from the SR. HRCBP is expressed exclusively in
      muscle tissues and binds calcium with low affinity and high capacity. In
      addition, HRCBP interacts with triadin, a protein associated with the ryanodine
      receptor and thought to be involved in calcium release. Its calcium binding
      properties, localization to the SR, and interaction with triadin suggest that
      HRCBP is involved in calcium handling by the SR. To determine the function of
      HRCBP in vivo, we inactivated HRC, the gene encoding HRCBP, in mice. HRC knockout
      mice exhibited impaired weight gain beginning at 11 months of age, which was
      marked by reduced skeletal muscle and fat mass, and triadin protein expression
      was upregulated in the heart of HRC knockout mice. In addition, HRC null mice
      displayed a significantly exaggerated response to the induction of cardiac
      hypertrophy by isoproterenol compared to their wild-type littermates. The
      exaggerated response of HRC knockout mice to the induction of cardiac hypertrophy
      is consistent with a regulatory role for HRCBP in calcium handling in vivo and
      suggests that mutations in HRC, in combination with other genetic or
      environmental factors, might contribute to pathological hypertrophy and heart
      failure.

PMID- 17030630
TI  - Conservative inheritance of newly synthesized DNA in double-strand break-induced
      gene conversion.
AB  - To distinguish among possible mechanisms of repair of a double-strand break (DSB)
      by gene conversion in budding yeast, Saccharomyces cerevisiae, we employed
      isotope density transfer to analyze budding yeast mating type (MAT) gene
      switching in G2/M-arrested cells. Both of the newly synthesized DNA strands
      created during gene conversion are found at the repaired locus, leaving the donor
      unchanged. These results support suggestions that mitotic DSBs are primarily
      repaired by a synthesis-dependent strand-annealing mechanism. We also show that
      the proportion of crossing-over associated with DSB-induced ectopic recombination
      is not affected by the presence of nonhomologous sequences at one or both ends of
      the DSB or the presence of additional sequences that must be copied from the
      donor.

PMID- 17030632
TI  - Editors and authors: a sacred trust.

PMID- 17030633
TI  - Milestones in oncology: introducing a new section.

PMID- 17030631
TI  - Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor
      substrate 1 (IRS-1) or IRS-2.
AB  - Insulin receptor substrates (IRSs) are signaling adaptors that play a major role
      in the metabolic and mitogenic actions of insulin and insulin-like growth
      factors. Reports have recently noted increased levels, or activity, of IRSs in
      many human cancers, and some have linked this to poor patient prognosis. We found
      that overexpressed IRS-1 was constitutively phosphorylated in vitro and in vivo
      and that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland
      showed progressive mammary hyperplasia, tumorigenesis, and metastasis. Tumors
      showed extensive squamous differentiation, a phenotype commonly seen with
      activation of the canonical beta-catenin signaling pathway. Consistent with this,
      IRSs were found to bind beta-catenin in vitro and in vivo. IRS-induced
      tumorigenesis is unique, given that the IRSs are signaling adaptors with no
      intrinsic kinase activity, and this supports a growing literature indicating a
      role for IRSs in cancer. This study defines IRSs as oncogene proteins in vivo and
      provides new models to develop inhibitors against IRSs for anticancer therapy.

PMID- 17030634
TI  - The legacy of great science: the work of Nobel Laureate Gertrude Elion lives on.

PMID- 17030635
TI  - Autobiography of Gertrude B. Elion, the Nobel Prize in Physiology or Medicine
      1988.

PMID- 17030636
TI  - The Colorectal Cancer Coalition: reflections on the future.

PMID- 17030637
TI  - New approaches to the adjuvant therapy of colon cancer.
AB  - Analysis of data from patients treated outside clinical trials suggests that
      adjuvant chemotherapy for stage II colon cancer provides less than a 3% absolute
      improvement in survival at 5 years. This is remarkably close to the small degree
      of benefit suggested by controlled studies. An overview of the data suggests that
      surgery alone cures approximately 75% of stage II patients. Between 20% and 25%
      of patients experience disease recurrence despite surgery and adjuvant
      chemotherapy, whereas adjuvant chemotherapy cures between 1% and 6%. In stage III
      patients, the benefit of adjuvant therapy is greater overall. The extent of
      benefit relates to tumor grade, invasion, and nodal involvement. Incorporation of
      molecular markers in the design of current trials may enable us to refine our
      identification of patients at highest risk of recurrence and hence those standing
      to gain most from adjuvant therapy.

PMID- 17030638
TI  - Therapy for metastatic colorectal cancer.
AB  - Median overall survival of metastatic colorectal cancer patients treated with
      first- and second-line combination chemotherapy now extends to more than 20
      months in some studies. Chemotherapy alone, particularly when oxaliplatin is
      included, may allow potentially curative resection of advanced disease. There is
      evidence that the addition of antibodies targeted against vascular endothelial
      growth factor or the epidermal growth factor receptor will further improve
      prospects for patients with advanced and metastatic disease. However, the optimum
      sequencing of chemo- and biological therapies remains to be established, as does
      the potential contribution of numerous agents in development.

PMID- 17030639
TI  - Genomics and the impact of new technologies on the management of colorectal
      cancer.
AB  - High-throughput genomic technologies have the potential to have a major impact on
      preclinical and clinical drug development and the selection and stratification of
      patients in clinical trials. These technologies, which are at varying stages of
      commercialization, include array-based comparative genomic hybridization, single
      nucleotide polymorphism arrays, and (the most mature example) expression-based
      arrays. One of the rate-limiting steps in the routine clinical application of
      expression array-based technology is the need for suitable clinical samples. One
      of the major challenges moving forward, therefore, relates to the ability to use
      formalin-fixed, paraffin-embedded--derived tissue in expression profiling-based
      approaches.

PMID- 17030640
TI  - The present and future of angiogenesis-directed treatments of colorectal cancer.
AB  - The level of angiogenic activity in colorectal tumors has been shown to be a
      determinant of survival. Recent trials established that, in both the first- and
      second-line treatment of metastatic colorectal cancer, the addition of the
      vascular endothelial growth factor (VEGF)-directed antibody bevacizumab to
      chemotherapy significantly prolongs survival compared to chemotherapy alone.
      Those trials provided proof of principle that inhibition of angiogenesis has the
      potential to enhance the effectiveness of treatment of this disease. Oral agents
      directed toward VEGF receptor signaling are in advanced development, but none to
      date has proven beneficial in phase III trials in advanced colorectal cancer.
      Additional trials are needed to determine if improved pharmacological
      characteristics of the small molecules can be modified to replicate the activity
      of the antibody or if mechanistic differences require a more specific approach.
      Since bevacizumab has minimal activity as a single agent, a key question for
      future therapeutic development relates to the interaction between antiangiogenic
      strategies and cytotoxic therapies. We hypothesize that bevacizumab may
      potentiate the efficacy of cytotoxics not solely by alterations of tumor
      interstitial pressure but also by promoting sensitivity to proapoptotic signals
      consequent upon nutrient and oxygen withdrawal.

PMID- 17030641
TI  - Nonsurgical approaches to colorectal cancer.
AB  - It is time to challenge the current orthodoxy that frowns upon surgical and
      nonsurgical methods of tumor reduction for patients with metastatic colon cancer.
      Although the studies conducted with radiofrequency ablation, chemoembolization,
      and radiation therapy in patients with metastatic colon cancer have tended to be
      small and may have been subject to selection bias, they have produced survival
      data that require careful consideration. At the very least, it is clear that
      locoregional approaches to debulking tumors are feasible and that their
      combination with systemic chemotherapy should be investigated.

PMID- 17030642
TI  - Update on capecitabine in colorectal cancer.
AB  - In combination chemotherapy for metastatic colorectal cancer, i.v. 5-fluorouracil
      (5-FU) can be replaced by oral 5-FU (in the form of capecitabine or another
      orally available analogue) without negatively affecting overall toxicity and
      without remarkably reducing the efficacy of treatment in terms of response rate
      or overall survival. Preclinical evidence of synergy has led to promising early
      and successfully completed studies combining capecitabine plus oxaliplatin with
      bevacizumab, cetuximab, and epidermal growth factor receptor tyrosine kinase
      inhibitors. The use of preoperative capecitabine plus radiation is achieving good
      rates of pathological complete response in rectal cancer. While capecitabine is
      generally well tolerated, its potential toxicities need careful management and
      may require individual dose adaption.

PMID- 17030643
TI  - Challenges in the use of epidermal growth factor receptor inhibitors in
      colorectal cancer.
AB  - Novel targeted agents increase the therapeutic armamentarium in metastatic
      colorectal cancer (mCRC). Monoclonal antibodies against the epidermal growth
      factor receptor (EGFR) are active against EGFR-expressing mCRC that is refractory
      to irinotecan. EGFR monoclonal antibodies also have promise in less advanced
      stages of CRC. Cetuximab and panitumumab are clearly active agents. It has been
      shown that cetuximab is more active when administered in combination with
      irinotecan. Phase II studies also report promising activity when monoclonal
      antibodies against the EGFR are combined with classic chemotherapeutic regimens
      in the first-line treatment of mCRC. However, the best means of scheduling such
      agents and integrating them with each other and with chemotherapy have yet to be
      established. The management of toxicity (particularly rash) and finding
      appropriate means of selecting patients pose additional challenges. While the
      occurrence of rash is associated with greater likelihood of response, EGFR
      staining by immunohistochemistry at baseline is not. For reasons that are not yet
      clear, the tyrosine kinase inhibitors of EGFR seem less effective than their
      monoclonal antibody counterparts in the therapy of mCRC.

PMID- 17030644
TI  - Novel therapeutic developments other than EGFR and VEGF inhibition in colorectal
      cancer.
AB  - Developments that may improve existing cytotoxic therapy for colorectal cancer
      (CRC) include alternatives to 5-fluorouracil (5-FU) such as the liposomal
      Thymidylate Synthase inhibitor OSI-7904L and the multitargeted antifolate
      pemetrexed. Studies have explored means of reformulating irinotecan, modulating
      its pharmacokinetics, and enhancing its activity by maximizing DNA damage through
      poly(ADP-ribose) polymerase inhibition. Cell cycle inhibitors may offer an
      alternative to combination with 5-FU. However, as standard regimens become more
      complex, so do the clinical trials needed to develop new agents, and the path to
      registration becomes ever more tortuous. It is therefore likely that several
      drugs with promise in CRC will not be developed for this indication.

PMID- 17030645
TI  - Referral to medical oncology: a crucial step in the treatment of older patients
      with stage III colon cancer.
AB  - PURPOSE: Adjuvant chemotherapy for stage III colon cancer produces a substantial
      survival benefit, but many older patients do not receive chemotherapy. This study
      examines factors associated with medical oncology consultation and evaluates the
      impact of such consultation on chemotherapy use. PATIENTS AND METHODS: We used
      the Surveillance Epidemiology and End Results-Medicare linked database and
      identified 7,569 patients, aged 66-99, with stage III colon cancer diagnosed from
      1992-1999. Modified Poisson regression was used to assess the relative risk for
      seeing a medical oncologist and for receiving chemotherapy as a function of
      individual characteristics. RESULTS: 78.08% of patients saw a medical oncologist
      within 6 months of diagnosis. Patients who were female, white, married, had low
      comorbidity scores, were diagnosed in more recent years, or had four or more
      positive lymph nodes were more likely to see a medical oncologist. Patients
      seeing a medical oncologist were 10 times more likely to receive chemotherapy
      (odds ratio, 9.98; 95% confidence interval, 8.21-12.14), after controlling for
      demographic and tumor characteristics. Chemotherapy use increased over time, but
      was substantially lower among older, black, and unmarried patients. CONCLUSIONS:
      Referral to medical oncology is one of the most important factors associated with
      receipt of chemotherapy among older patients with stage III colon cancer.
      Comorbidity decreases the likelihood of receiving chemotherapy, but its effect is
      the same for those who see a medical oncologist and all patients combined.
      Ensuring that high-risk patients are referred to medical oncology is a crucial
      step in quality care for patients with colon cancer.

PMID- 17030646
TI  - Photodynamic therapy in oncology.
AB  - Photodynamic therapy (PDT) is increasingly being recognized as an attractive,
      alternative treatment modality for superficial cancer. Treatment consists of two
      relatively simple procedures: the administration of a photosensitive drug and
      illumination of the tumor to activate the drug. Efficacy is high for small
      superficial tumors and, except for temporary skin photosensitization, there are
      no long-term side effects if appropriate protocols are followed. Healing occurs
      with little or no scarring and the procedure can be repeated without cumulative
      toxicity. Considering the efficacy and lack of long-term toxicity of PDT, and the
      fact that the first treatment of cancer with PDT was done more than 100 years
      ago, one might expect that this treatment had already become an established
      therapy. However, PDT is currently offered in only a few selected centers,
      although it is slowly gaining acceptance as an alternative to conventional cancer
      therapies. Here, we show the developmental steps PDT underwent and summarize the
      current clinical applications. The data show that, when properly used, PDT is an
      effective alternative treatment option in oncology.

PMID- 17030647
TI  - The molecular perspective: alcohol.

PMID- 17030649
TI  - Natalizumab and immune cells.

PMID- 17030648
TI  - Mediterranean diet, Alzheimer disease, and vascular mediation.
AB  - OBJECTIVES: To examine the association between the Mediterranean diet (MeDi) and
      Alzheimer disease (AD) in a different AD population and to investigate possible
      mediation by vascular pathways. Design, Setting, Patients, and MAIN OUTCOME
      MEASURES: A case-control study nested within a community-based cohort in New
      York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores
      indicating higher adherence) was the main predictor of AD status (194 patients
      with AD vs 1790 nondemented subjects) in logistic regression models that were
      adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype,
      caloric intake, smoking, medical comorbidity index, and body mass index
      (calculated as weight in kilograms divided by height in meters squared). We
      investigated whether there was attenuation of the association between MeDi and AD
      when vascular variables (stroke, diabetes mellitus, hypertension, heart disease,
      lipid levels) were simultaneously introduced in the models (which would
      constitute evidence of mediation). RESULTS: Higher adherence to the MeDi was
      associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval,
      0.67-0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects
      in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval,
      0.29-0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence
      interval, 0.17-0.59) for AD (P for trend <.001). Introduction of the vascular
      variables in the model did not change the magnitude of the association.
      CONCLUSIONS: We note once more that higher adherence to the MeDi is associated
      with a reduced risk for AD. The association does not seem to be mediated by
      vascular comorbidity. This could be the result of either other biological
      mechanisms (oxidative or inflammatory) being implicated or measurement error of
      the vascular variables.

PMID- 17030650
TI  - Acidotoxicity trumps excitotoxicity in ischemic brain.

PMID- 17030651
TI  - Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid
      and glutamate alterations.
AB  - Impairments in certain cognitive functions mediated by the dorsolateral
      prefrontal cortex, such as working memory, are core features of schizophrenia.
      Convergent findings suggest that these disturbances are associated with
      alterations in markers of inhibitory gamma-aminobutyric acid and excitatory
      glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically,
      reduced gamma-aminobutyric acid synthesis is present in the subpopulation of
      gamma-aminobutyric acid neurons that express the calcium-binding protein
      parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the
      resulting impaired inhibitory regulation of pyramidal neurons contributes to a
      reduction in the synchronized neuronal activity that is required for working
      memory function. Several lines of evidence suggest that these changes may be
      either secondary to or exacerbated by impaired signaling via the N-methyl-d
      aspartate class of glutamate receptors. These findings suggest specific targets
      for therapeutic interventions to improve cognitive function in individuals with
      schizophrenia.

PMID- 17030653
TI  - Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated
      patients with multiple sclerosis.
AB  - BACKGROUND: Treatment with natalizumab, a monoclonal antibody against the
      adhesion molecule very late activation antigen 4, an alpha4beta(1) integrin, was
      recently associated with the development of progressive multifocal
      leukoencephalopathy, a demyelinating disorder of the central nervous system
      caused by JC virus infection. OBJECTIVE: To test the effect of natalizumab
      treatment on the CD4(+)/CD8(+) T-cell ratios in cerebrospinal fluid (CSF) and
      peripheral blood. DESIGN: Prospective longitudinal study. SETTING: Academic and
      private multiple sclerosis centers. PATIENTS: Patients with multiple sclerosis
      (MS) treated with natalizumab, untreated patients with MS, patients with other
      neurologic diseases, and human immunodeficiency virus-infected patients. MAIN
      OUTCOME MEASURES: CD4(+) and CD8(+) T cells were enumerated in CSF and peripheral
      blood. The mean fluorescence intensity of unbound alpha4 integrin on peripheral
      blood CD4(+) and CD8(+) T cells was analyzed before and after natalizumab
      therapy. RESULTS: Natalizumab therapy decreased the CSF CD4(+)/CD8(+) ratio of
      patients with MS to levels similar to those of human immunodeficiency virus
      infected patients. CD4(+)/CD8(+) ratios in peripheral blood in patients with MS
      progressively decreased with the number of natalizumab doses, but they remained
      within normal limits. Six months after the cessation of natalizumab therapy, CSF
      CD4(+)/CD8(+) ratios normalized. The expression of unbound alpha4 integrin on
      peripheral blood T cells decreases with natalizumab therapy and was significantly
      lower on CD4(+) vs CD8(+) T cells. CONCLUSIONS: Natalizumab treatment alters the
      CSF CD4(+)/CD8(+) ratio. Lower expression of unbound alpha4 integrin on CD4(+) T
      cells is one possible mechanism. These results may have implications for the
      observation that some natalizumab-treated patients with MS developed progressive
      multifocal leukoencephalopathy.

PMID- 17030654
TI  - Neuromyelitis optica IgG status in acute partial transverse myelitis.
AB  - BACKGROUND: Neuromyelitis optica (NMO) IgG is a specific marker for NMO.
      Furthermore, a high proportion of patients with longitudinally extensive
      transverse myelitis (characterized by spinal cord lesions extending 3 vertebral
      segments or more on magnetic resonance imaging) are seropositive for NMO-IgG and
      are considered to have a limited form of NMO. The NMO-IgG status in mild cases of
      acute partial transverse myelitis asociated with minimal magnetic resonance
      imaging abnormalities (spinal cord lesions <2 vertebral segments on magnetic
      resonance imaging) is unknown. OBJECTIVE: To investigate the NMO-IgG status of
      patients with acute partial transverse myelitis and a normal cerebral magnetic
      resonance image. DESIGN: Observational, retrospective consecutive case series
      with longitudinal follow-up. SETTING: Allegheny Multiple Sclerosis Treatment
      Center. PATIENTS: Three groups of patients were tested for NMO-IgG. Group 1
      consisted of 22 patients with acute partial transverse myelitis, group 2
      consisted of 4 patients with definite NMO (by 1999 criteria of Wingerchuk et al),
      and group 3 consisted of 6 patients with definite multiple sclerosis. MAIN
      OUTCOME MEASURE: NMO-IgG status. A commercially available assay for NMO
      antibodies was performed at the Mayo Clinic. Testing was performed during the
      convalescent stage of the illness. RESULTS: Of the 22 patients with acute partial
      transverse myelitis, only 1 was seropositive for NMO-IgG at presentation. This
      patient subsequently developed recurrent episodes of longitudinally extensive
      transverse myelitis that are typicaly seen in association with NMO-IgG. Three of
      the 4 patients meeting criteria for NMO were seropositive. None of the patients
      with multiple sclerosis had NMO-IgG detected. CONCLUSION: NMO-IgG is rarely
      encountered in patients with acute partial transverse myelitis, which is in sharp
      contrast to the high frequency of this antibody in patients with NMO and
      longitudinally extensive transverse myelitis.

PMID- 17030655
TI  - Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer
      disease: OmegAD study: a randomized double-blind trial.
AB  - BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or
      fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and
      eicosapentaenoic acid, may prevent Alzheimer disease (AD). OBJECTIVE: To
      determine effects of dietary omega-3 fatty acid supplementation on cognitive
      functions in patients with mild to moderate AD. DESIGN: Randomized, double-blind,
      placebo-controlled clinical trial. PARTICIPANTS: Two hundred four patients with
      AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while
      receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental
      State Examination (MMSE) score of 15 points or more were randomized to daily
      intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega
      3 fatty acid-treated group) or placebo for 6 months, after which all received
      omega-3 fatty acid supplementation for 6 months more. MAIN OUTCOME MEASURES: The
      primary outcome was cognition measured with the MMSE and the cognitive portion of
      the Alzheimer Disease Assessment Scale. The secondary outcome was global function
      as assessed with the Clinical Dementia Rating Scale; safety and tolerability of
      omega-3 fatty acid supplementation; and blood pressure determinations. RESULTS:
      One hundred seventy-four patients fulfilled the trial. At baseline, mean values
      for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the
      Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6
      months, the decline in cognitive functions as assessed by the latter 2 scales did
      not differ between the groups. However, in a subgroup (n = 32) with very mild
      cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE
      decline rate was observed in the omega-3 fatty acid-treated group compared with
      the placebo group. A similar arrest in decline rate was observed between 6 and 12
      months in this placebo subgroup when receiving omega-3 fatty acid
      supplementation. The omega-3 fatty acid treatment was safe and well tolerated.
      CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to
      moderate AD did not delay the rate of cognitive decline according to the MMSE or
      the cognitive portion of the Alzheimer Disease Assessment Scale. However,
      positive effects were observed in a small group of patients with very mild AD
      (MMSE >27 points).

PMID- 17030656
TI  - Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases.
AB  - BACKGROUND: Some patients with systemic lupus erythematosus have selective loss
      of small-diameter nerve fibers, while larger nerve fibers are unaffected.
      OBJECTIVE: To determine intraepidermal nerve fiber densities in patients with
      different chronic inflammatory autoimmune diseases. DESIGN: Cross-sectional
      study. SETTING: Stavanger University Hospital, Stavanger, and Haukeland
      University Hospital, Haukeland, Norway. PATIENTS: Sixty patients with systemic
      lupus erythematosus (SLE) (mean +/- SD age, 43.2 +/- 13.5 years), 61 patients
      with primary Sjogren syndrome (age, 57.1 +/- 14.7 years), and 52 patients with
      rheumatoid arthritis (age, 57.4 +/- 12.3 years) were compared with 106 healthy
      subjects (age, 49.0 +/- 19.6 years). INTERVENTIONS: Skin biopsy specimens. MAIN
      OUTCOME MEASURES: To evaluate small-diameter nerve fiber loss, intraepidermal
      nerve fiber densities were measured in skin punch biopsy specimens obtained from
      the distal part of the leg. RESULTS: The mean +/- SD densities were 7.5 +/- 3.8
      fibers/mm in patients with SLE, 9.2 +/- 3.8 fibers/mm in primary Sjogren
      syndrome, and 10.9 +/- 5.4 fibers/mm in rheumatoid arthritis vs 12.4 +/- 4.6
      fibers/mm in healthy subjects. Densities were significantly less in patients with
      SLE vs patients with rheumatoid arthritis and vs healthy subjects (P<.001 for
      both), as well as in patients with primary Sjogren syndrome vs healthy subjects
      (P<.001). Eight patients (13%) with SLE, 2 patients (3%) with primary Sjogren
      syndrome, and 2 patients (4%) with rheumatoid arthritis had densities below the
      lower reference limit of 3.4 fibers/mm, consistent with small-diameter nerve
      fiber neuropathy. CONCLUSION: The degree of loss of small-diameter nerve fibers
      differs among patients with these chronic inflammatory autoimmune diseases,
      likely reflecting differences in pathogenesis and organ affinity of the
      individual disease entities.

PMID- 17030657
TI  - Calf-head sign in Miyoshi myopathy.
AB  - OBJECTIVE: To observe whether patients with Miyoshi-type dysferlinopathy
      demonstrate any distinct appearance in the back of the shoulders and upper back
      in a specific posture. DESIGN: Case series. SETTING: Neurology outpatient clinic
      of a north Indian tertiary care medical institute. PATIENTS: Fifteen patients
      from 9 families (10 males and 5 females; age range, 16-42 years) who had Miyoshi
      myopathy with onset of calf and shin muscle wasting between the ages of 9 and 28
      years and a myopathic pattern at electromyography, moderately high serum creatine
      kinase levels, and absence of dysferlin at immunohistochemical staining.
      INTERVENTIONS: Patients were asked to raise their arms with shoulders abducted
      and elbows flexed to 90 degrees . All were observed from behind for the
      morphological change in the bulk of different muscles of the upper back and
      shoulders. T1-weighted magnetic resonance imaging of the upper thorax and
      shoulder was performed in an oblique sagittal plane to confirm the clinical
      findings. MAIN OUTCOME MEASURE: Consistent pattern of muscle enlargement or
      wasting seen clinically and at magnetic resonance imaging that produces a
      particular diagnostic appearance. RESULTS: A characteristic appearance was
      observed on the upper back and shoulders that could be described as calf heads on
      a trophy sign. The sign was clearly visible in 6 patients, whereas it was present
      in a subtle manner in another 4. Some but not all components of the sign were
      visible in the rest of the patients. CONCLUSION: The calf heads on a trophy sign
      may be useful in identifying most patients with Miyoshi-type dysferlinopathy.

PMID- 17030658
TI  - Composite SISCOM perfusion patterns in right and left temporal seizures.
AB  - OBJECTIVE: To compare composite subtraction ictal single-photon emission computed
      tomography coregistered to magnetic resonance imaging (also known as SISCOM)
      patterns between right and left medial temporal-onset seizures to document
      neuroanatomical involvement in perfusion patterns. DESIGN: A retrospective
      comparative survey. SETTING: Epilepsy monitoring unit in a tertiary care referral
      center. PARTICIPANTS: Subjects with temporal lobe epilepsy (TLE) who underwent
      ictal single-photon emission computed tomography studies. MAIN OUTCOME MEASURES:
      Comparison of ictal perfusion pattern changes in subjects with right and left
      temporal seizures. RESULTS: Composite subtraction ictal single-photon emission
      computed tomography coregistered to magnetic resonance images showed similar
      regions of hyperperfusion change in the ipsilateral anteromedial temporal-corpus
      striatum-insula region in both groups. In the midbrain reticular formation, there
      was a significant difference in hyperperfusion between the left and right TLE
      groups. In addition, the right, but not the left, TLE group shows contralateral
      hypoperfusion of the temporoparietal junction. CONCLUSIONS: While anteromedial
      temporal-corpus striatum-insula perfusion patterns are similar, there are
      brainstem and hemispheric perfusion pattern differences in right and left TLE
      seizures, confirming pathophysiological differences between the groups. These
      findings help define neuronal network involvement in TLE seizures, and may
      explain the differences in clinical symptoms of right and left TLE seizures.

PMID- 17030660
TI  - Measurements of the amygdala and hippocampus in pathologically confirmed
      Alzheimer disease and frontotemporal lobar degeneration.
AB  - BACKGROUND: Differentiating between Alzheimer disease (AD) and frontotemporal
      lobar degeneration (FTLD) can be difficult, particularly in the earliest stages
      of the diseases. Patterns of atrophy on magnetic resonance imaging may help
      distinguish these diseases and aid diagnosis. OBJECTIVE: To assess the diagnostic
      utility of magnetic resonance imaging-derived amygdala and hippocampal volumes
      from patients with pathologically proved AD and FTLD. DESIGN: Cross-sectional
      volumetric magnetic resonance imaging study of the hippocampus and amygdala.
      SETTING: Specialist cognitive disorders clinic. Subjects Thirty-seven subjects,
      including 10 patients with pathologically proved AD, 17 patients with
      pathologically proved FTLD, and 10 age-matched control subjects. MAIN OUTCOME
      MEASURES: Hippocampal and amygdala volumes. RESULTS: Geometric mean amygdala and
      hippocampal volumes were, respectively, 15.0% (95% confidence interval [CI], 4.2%
      24.5%) and 16.4% (95% CI, 5.9%-25.6%) lower in the AD than in the control group.
      In FTLD, the equivalent differences were 43.1% (95% CI, 31.9%-52.6%) in the
      amygdala and 36.1% (95% CI, 27.5%-43.7%) in the hippocampus. Volumes were
      significantly lower in the FTLD than in the AD group (P<.01 in both regions).
      Within the FTLD clinical subgroups, there was evidence of a difference in pattern
      of atrophy with greater asymmetry (left smaller than right) in semantic dementia
      compared with frontal variant FTLD (P<.001). On average, the left hippocampus was
      14% smaller in semantic dementia than in frontal variant FTLD, whereas the right
      hippocampus was 37% larger. On average, the left amygdala was 39% smaller in
      semantic dementia than in frontal variant FTLD, whereas the right amygdala was
      only 1% smaller. CONCLUSIONS: Hippocampal atrophy is not specific to AD or FTLD.
      However, severe or asymmetrical amygdala atrophy should suggest FTLD. Atrophy
      patterns follow clinical syndromes rather than pathology.

PMID- 17030661
TI  - Cognitive impairment and celiac disease.
AB  - OBJECTIVE: To characterize the clinical, radiological, and electrophysiological
      laboratory profiles and histological features of patients who developed cognitive
      impairment temporally associated with celiac disease. DESIGN: Case series.
      SETTING: Referral center. PATIENTS: Patients with the onset of progressive
      cognitive decline within 2 years of symptomatic onset or with a severe
      exacerbation of biopsy-proved adult celiac disease were identified from the Mayo
      Clinic medical records from January 1, 1970, to December 31, 2005. Patients were
      excluded if an alternate cause of their cognitive impairment was identified.
      RESULTS: Thirteen patients (5 women) were identified. The median age at cognitive
      impairment onset was 64 years (range, 45-79 years), which coincided with symptom
      onset or exacerbation of diarrhea, steatorrhea, and abdominal cramping in 5
      patients. Amnesia, acalculia, confusion, and personality changes were the most
      common presenting features. The average initial Short Test of Mental Status score
      was 28 of a total of 38 (range, 18-34), which was in the moderately impaired
      range. The results of neuropsychological testing suggested a trend of a
      frontosubcortical pattern of impairment. Ten patients had ataxia, and 4 of them
      also had peripheral neuropathy. Magnetic resonance imaging of the head showed
      nonspecific T2 hyperintensities, and electroencephalography showed nonspecific
      diffuse slowing. Deficiencies in folate, vitamin B(12), vitamin E, or a
      combination were identified in 4 patients, yet supplementation did not improve
      their neurological symptoms. Three patients improved or stabilized cognitively
      with gluten withdrawal. A detailed histological analysis revealed nonspecific
      gliosis. CONCLUSIONS: A possible association exists between progressive cognitive
      impairment and celiac disease, given the temporal relationship and the relatively
      high frequency of ataxia and peripheral neuropathy, more commonly associated with
      celiac disease. Given the impact for potential treatment of similar cases,
      recognition of this possible association and additional studies are warranted.

PMID- 17030659
TI  - Visual hallucinations in posterior cortical atrophy.
AB  - BACKGROUND: Visual hallucinations have been reported to occur in up to 25% of
      patients who meet the criteria for posterior cortical atrophy (PCA). It is not
      known, however, whether patients who meet the criteria for PCA and have
      hallucinations are different from those who meet the criteria and do not have
      hallucinations. OBJECTIVE: To compare the clinical and imaging features of
      patients with PCA with and without well-formed visual hallucinations. DESIGN:
      Case-control study. SETTING: Tertiary care medical center. PATIENTS: Fifty-nine
      patients fulfilling the criteria for PCA were retrospectively identified and
      divided into 2 groups based on the presence (n = 13) or absence (n = 46) of
      visual hallucinations. MAIN OUTCOME MEASURES: Statistically significant clinical
      differences and imaging differences using voxel-based morphometry between the 2
      groups. RESULTS: In patients with PCA and hallucinations, parkinsonism and rapid
      eye movement sleep behavior disorder occurred more frequently, as did myoclonic
      jerks (P<.001 for both). Voxel-based morphometry showed greater atrophy in a
      network of structures, including the primary visual cortex, lentiform nuclei,
      thalamus, basal forebrain, and midbrain, in patients with hallucinations.
      CONCLUSIONS: Hallucinations in patients with PCA are associated with
      parkinsonism, rapid eye movement sleep behavior disorder, and myoclonic jerks.
      The voxel-based morphometry results suggest that hallucinations in PCA cannot be
      exclusively attributed to atrophy of the posterior association cortices and may
      involve a circuit of thalamocortical connections.

PMID- 17030662
TI  - The progression of cognition, psychiatric symptoms, and functional abilities in
      dementia with Lewy bodies and Alzheimer disease.
AB  - BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common
      forms of dementia, relatively little is known about its cognitive and functional
      course. OBJECTIVE: To compare change over time in general cognitive status,
      memory test performance, psychiatric symptoms, neurological signs, and functional
      abilities in patients with probable DLB and probable Alzheimer disease (AD).
      DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited
      into the study from 3 sites. Patients with AD (n = 55) were selected from a
      larger cohort and matched 2 to 1 to the patients with DLB on age and baseline
      global cognitive status. Patients were followed up at 6-month intervals for an
      average of 6.2 visits and assessed at each visit with tests of global cognitive
      functioning and verbal learning and memory and measures of psychiatric,
      neurological, and functional status. RESULTS: At the baseline evaluation,
      patients with DLB performed more poorly on a measure of constructional praxis and
      all measures of functional status. They also had more severe psychiatric symptoms
      and neurological signs than the AD group. Despite these initial differences,
      generalized estimating equations applied to regression analyses with repeated
      measures determined that the only difference between the 2 groups in change in
      cognitive test performance was on a measure of recognition memory; patients with
      AD declined, while patients with DLB remained relatively stable. Patients with
      DLB had relatively stable behavioral symptoms and visual illusions, whereas
      patients with AD had a significant increase in these symptoms over time.
      Neurological and functional changes over time were similar in the 2 groups.
      CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB
      and patients with AD were noted; these have implications for clinical diagnosis
      and treatment.

PMID- 17030663
TI  - Tauopathy-like abnormalities and neurologic deficits in mice immunized with
      neuronal tau protein.
AB  - BACKGROUND: A possible role of autoimmunity in Alzheimer disease pathogenesis has
      recently attracted increasing attention. Vaccination with amyloid-beta peptide
      was reported to cause marked reduction in amyloid deposition, but it also induced
      encephalitis. Not much is known regarding neurofibrillary tangle-related
      autoimmune effects. OBJECTIVE: To use the main component of tangles-microtubule
      associated tau protein-to test the feasibility of active induction of a
      neuroautoimmune disorder in mice. DESIGN: Prospective, randomized controlled
      animal study. SETTING: University medical center research laboratory. Subjects
      Female C57BL/6 mice. INTERVENTIONS: Inoculation with recombinant human tau
      protein emulsified in complete Freund adjuvant and with pertussis toxin. MAIN
      OUTCOME MEASURES: Clinical, immunologic, pathologic, and behavioral evaluations
      were performed. RESULTS: Vaccination with tau protein induced histopathologic
      features of Alzheimer disease and tauopathies, indicated by the presence of
      neurofibrillary tangle-like structures, axonal damage, and gliosis. Also,
      mononuclear infiltrates without demyelination in the central nervous system,
      accompanied by neurologic deficits (such as a limp tail and limb paralysis), were
      observed. Anti-tau antibodies were detected in the serum of tau-immunized mice.
      CONCLUSIONS: These results provide a link between tau autoimmunity and tauopathy
      like abnormalities and indicate potential dangers of using tau for immunotherapy.
      This experimental autoimmune tauopathy-like model is due to a pathogenic immune
      response against an intraneuronal antigen and is not related to myelin antigens.

PMID- 17030664
TI  - Magnetic resonance neurography in extraspinal sciatica.
AB  - BACKGROUND: Sciatica without evidence of lumbosacral root compression is often
      attributed to piriformis syndrome. However, specific diagnostic tools have not
      been available to demonstrate sciatic nerve entrapment by the piriformis muscle.
      OBJECTIVE: To evaluate the use of magnetic resonance (MR) neurography in
      identifying abnormalities of the sciatic nerve in patients with unexplained
      sciatica. DESIGN: Case series from a retrospective medical record review.
      PATIENTS: Fourteen patients with sciatic distribution pain and normal results on
      MR imaging for lumbosacral radiculopathy were referred for MR neurography of the
      lumbosacral plexus and sciatic nerves. RESULTS: In 12 patients, MR neurography
      demonstrated increased fluid-attenuated inversion recovery signal in the
      ipsilateral sciatic nerve. In most patients, this abnormal signal was seen at the
      sciatic notch, at or just inferior to the level of the piriformis muscle. To
      date, 4 patients have undergone surgical decompression, with excellent relief of
      symptoms in 3 of them. CONCLUSION: Magnetic resonance neurography often
      identifies an abnormal increased signal in the proximal sciatic nerve in patients
      with extraspinal sciatica and allows more accurate diagnosis of sciatic nerve
      entrapment in suspected cases.

PMID- 17030665
TI  - Reversible posterior leukoencephalopathy syndrome after bevacizumab/FOLFIRI
      regimen for metastatic colon cancer.
AB  - OBJECTIVE: To describe a patient with reversible posterior leukoencephalopathy
      syndrome following the administration of bevacizumab (Avastin), a monoclonal
      antibody against vascular endothelial growth factor. DESIGN: Case
      report/literature review. SETTING: University hospital. PATIENT: A 52-year-old
      man receiving chemotherapy for stage IV rectal carcinoma. RESULTS: Clinical and
      radiographic evidence consistent with reversible posterior leukoencephalopathy
      syndrome was found following the administration of irinotecan hydrochloride,
      leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy and
      bevacizumab. CONCLUSIONS: Reversible posterior leukoencephalopathy syndrome
      following treatment with angiogenesis modulators can occur. In addition to
      raising clinical suspicion in appropriate patients, this report may yield clues
      to the pathophysiologic underpinnings of reversible posterior leukoencephalopathy
      syndrome.

PMID- 17030666
TI  - Betamethasone and improvement of neurological symptoms in ataxia-telangiectasia.
AB  - BACKGROUND: To our knowledge, there have been no reports on the control of
      central nervous system symptoms in patients with ataxia-telangiectasia.
      OBJECTIVE: To preliminarily determine the effectiveness of corticosteroid therapy
      on the central nervous system symptoms of a child with ataxia-telangiectasia in
      whom neurological signs improved when, occasionally, he was given betamethasone
      to treat asthmatic bronchitis attacks. DESIGN: Case report. SETTING: Tertiary
      care hospital. Patient A 3-year-old boy with the classic hallmarks and a proved
      molecular diagnosis of ataxia-telangiectasia. INTERVENTIONS: We used
      betamethasone, 0.1 mg/kg per 24 hours, divided every 12 hours, for 4 weeks to
      preliminarily determine its effectiveness on the child's central nervous system
      symptoms and its safety. Methylprednisolone, 2 mg/kg per 24 hours, divided every
      12 hours, was then given in an attempt to perform a long-term treatment. RESULTS:
      There were improvements in the child's neurological symptoms 2 or 3 days after
      the beginning of the drug treatment. After 2 weeks of treatment, the improvement
      was dramatic: the disturbance of stance and gait was clearly reduced, and the
      control of the head and neck had increased, as had control of skilled movements.
      At 4 weeks of treatment, adverse effects mainly included increased appetite and
      body weight and moon face. No beneficial effect was obtained when, after 4 weeks,
      betamethasone was replaced with methylprednisolone. Six months later, without
      therapy, the child continued to experience severe signs of central nervous system
      impairment. CONCLUSION: Controlled studies to better understand the most
      appropriate drug and therapeutic schedule are required.

PMID- 17030667
TI  - T313M PINK1 mutation in an extended highly consanguineous Saudi family with early
      onset Parkinson disease.
AB  - BACKGROUND: To date, 5 well-confirmed genes for Parkinson disease (PD) have been
      identified, including 3 autosomal recessive genes: PTEN-induced putative kinase 1
      (PINK1), parkin, and DJ-1. Almost nothing is known about the genetics of PD in
      Saudi Arabia; however, consanguineous families, not infrequent in this
      population, could be important in the evaluation of known PD genes and the search
      for new PD factors in the future. OBJECTIVE: To investigate known recessive PD
      genes in 5 consanguineous Saudi families with PD. DESIGN: The entire open frame
      as well as the untranslated region and all 5' and 3' intron-exon boundaries of
      the PINK1, parkin, and DJ-1 genes were sequenced in 5 probands in Saudi families.
      RESULTS: Four of 5 probands tested negative for PINK1, parkin, and DJ-1
      mutations. However, in a large Saudi family with PD with at least 3
      consanguineous marriages between first cousins, we detected a threonine to
      methionine substitution at codon 313 (T313M) PINK1 mutation that affected the
      kinase domain. Manifestations of the disease in this family included early onset
      (age, 28-38 years), tremulous movement, slow progression, diurnal fluctuations,
      bradykinesia, good response to levodopa therapy, and only mild dyskinesias. A
      neurologist blinded to genetic status clinically evaluated 15 family members, all
      older than 20 years, and diagnosed PD only in individuals who were later found to
      be homozygous for the T313M mutation. None of the 13 heterozygotes demonstrated
      any sign of PD. CONCLUSION: A homozygous T313M mutation is responsible for PD in
      this large Saudi family. However, the heterozygous T313M mutation does not act as
      a PD susceptibility factor, which is in contrast to several reports of mutations
      affecting only 1 PINK1 allele discovered in sporadic PD.

PMID- 17030668
TI  - Cluster breathing associated with bihemispheric infarction and sparing of the
      brainstem.
AB  - OBJECTIVE: To report cluster breathing pattern associated with a nonbrainstem
      lesion. DESIGN: Case report. SETTING: Neurointensive care unit, St Mary's
      Hospital, Rochester, Minn. PATIENT: A patient with subarachnoid hemorrhage
      developed severe, diffuse, distal bilateral middle cerebral artery vasospasm with
      resultant cortical laminar necrosis and transient cluster breathing. Intervention
      Magnetic resonance imaging revealed bihemispheric lesions but no brainstem
      lesion. CONCLUSION: Cluster breathing may occur with nonbrainstem lesions.

PMID- 17030669
TI  - POMGnT1 mutations in congenital muscular dystrophy: genotype-phenotype
      correlation and expanded clinical spectrum.
AB  - BACKGROUND: Muscle-eye-brain disease is a congenital muscular dystrophy with eye
      and brain involvement due to POMGnT1 mutations. OBJECTIVE: To describe the
      clinical and molecular features of 3 Italian patients with POMGnT1 mutations.
      DESIGN: Case reports. PATIENTS: One patient had muscle and brain abnormalities
      without eye involvement. Two patients had a classic muscle-eye-brain disease
      phenotype with different levels of clinical severity. RESULTS: Brain magnetic
      resonance imaging showed cortical malformation and posterior fossa involvement.
      Immunofluorescence for glycosylated alpha-dystroglycan performed on muscle biopsy
      specimens demonstrated an absent signal in 1 patient and reduced staining in 2
      patients. Molecular analysis identified 5 mutations, 2 of which are novel.
      CONCLUSION: This article adds to what is known about the genotype-phenotype
      correlation and expands our awareness of the clinical spectrum associated with
      POMGnT1 mutations.

PMID- 17030670
TI  - Bradycardia after coiling of giant vertebral aneurysm.

PMID- 17030671
TI  - Bilateral pontine infarction secondary to basilar trunk saccular aneurysm.

PMID- 17030672
TI  - Vein of galen aneurysmal malformation.

PMID- 17030673
TI  - Diabetic neuropathies.

PMID- 17030674
TI  - Nonstroke treatment.

PMID- 17030675
TI  - Potassium-retaining diuretics and incident Alzheimer disease.

PMID- 17030676
TI  - Benign tremulous parkinsonism?

PMID- 17030677
TI  - Blood pressure in mutant rats lacking the 5-hydroxytryptamine transporter.

PMID- 17030678
TI  - Anabolic deficiency in men with chronic heart failure: prevalence and detrimental
      impact on survival.
AB  - BACKGROUND: The age-related decline of circulating anabolic hormones in men is
      associated with increased morbidity and mortality. We studied the prevalence and
      prognostic consequences of deficiencies in circulating total testosterone (TT)
      and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like
      growth factor-1 (IGF-1) in men with chronic heart failure (CHF). METHODS AND
      RESULTS: Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in
      208 men with CHF (median age 63 years; median left ventricular ejection fraction
      33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366
      healthy men. Serum levels of free testosterone were estimated (eFT) from levels
      of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF
      1, defined as serum levels at or below the 10th percentile of healthy peers, were
      seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely
      related to New York Heart Association class irrespective of cause (all P<0.01).
      DHEAS correlated positively with left ventricular ejection fraction and inversely
      with N-terminal pro-brain natriuretic peptide (both P<0.01). Circulating TT, eFT,
      DHEAS, and IGF-1 levels were prognostic markers in multivariable models when
      adjusted for established prognostic factors (all P<0.05). Men with CHF and normal
      levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI
      67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI
      65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival
      rate, 95% CI 5% to 49%) anabolic endocrine axes (P<0.0001). CONCLUSIONS: In male
      CHF patients, anabolic hormone depletion is common, and a deficiency of each
      anabolic hormone is an independent marker of poor prognosis. Deficiency of >1
      anabolic hormone identifies groups with a higher mortality.

PMID- 17030679
TI  - Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose
      oxidation and protects the heart from ischemic injury.
AB  - BACKGROUND: Acute pharmacological inhibition of cardiac malonyl coenzyme A
      decarboxylase (MCD) protects the heart from ischemic damage by inhibiting fatty
      acid oxidation and stimulating glucose oxidation. However, it is unknown whether
      chronic inhibition of MCD results in altered cardiac function, energy metabolism,
      or ischemic cardioprotection. METHODS AND RESULTS: Mcd-deficient mice were
      produced and assessed for in vivo cardiac function as well as ex vivo cardiac
      function, energy metabolism, and ischemic tolerance. In vivo and ex vivo cardiac
      function was similar in wild-type and mcd-/- mice. Ex vivo working hearts from
      mcd-/- and wild-type mice displayed no significant differences in rates of fatty
      acid oxidation, glucose oxidation, or glycolysis. However, cardiac deletion of
      mcd resulted in an increased expression of genes regulating fatty acid
      utilization that may compensate for the loss of MCD protein and likely
      contributes to the absence of changes in energy metabolism in the aerobic heart.
      Despite the lack of changes in fatty acid utilization, hearts from mcd-/- mice
      displayed a marked preference for glucose utilization after ischemia, which
      correlated with a significant cardioprotection of ischemic hearts from mcd-/-
      mice compared with wild-type mice. CONCLUSIONS: Deletion of MCD markedly
      increases glucose oxidation and improves functional recovery of the heart after
      ischemia. As a result, chronic pharmacological inhibition of MCD may be a viable
      approach to treat myocardial ischemia.

PMID- 17030680
TI  - Results from the Loire-Ardeche-Drome-Isere-Puy-de-Dome (LADIP) trial on atrial
      flutter, a multicentric prospective randomized study comparing amiodarone and
      radiofrequency ablation after the first episode of symptomatic atrial flutter.
AB  - BACKGROUND: There is no published randomized study comparing amiodarone therapy
      and radiofrequency catheter ablation (RFA) after only 1 episode of symptomatic
      atrial flutter (AFL). The aim of the Loire-Ardeche-Drome-Isere-Puy-de-Dome
      (LADIP) Trial of Atrial Flutter was 2-fold: (1) to prospectively compare first
      line RFA (group I) versus cardioversion and amiodarone therapy (group II) after
      only 1 AFL episode; and (2) to determine the impact of both treatments on the
      long-term risk of subsequent atrial fibrillation (AF). METHODS AND RESULTS: From
      October 2002 to February 2006, 104 patients (aged 78+/-5 years; 20 women) with
      AFL were included, with 52 patients in group I and 52 patients in group II. The
      cumulative risk of AFL or AF was interpreted with the use of Kaplan-Meier curves
      and compared by the log-rank test. Clinical presentation, echocardiographic data,
      and follow-up were as follows: age (78.5+/-5 versus 78+/-5 years), history of AF
      (27% versus 21.6%); structural heart disease (58% versus 65%), left ventricular
      ejection fraction (56+/-14% versus 54.5+/-14%), left atrial size (43+/-7 versus
      43+/-6 mm), mean follow-up (13+/-6 versus 13+/-6 months; P=NS), recurrence of AFL
      (3.8% versus 29.5%; P<0.0001), and occurrence of significant AF beyond 10 minutes
      (25% versus 18%; P=0.3). Five complications (10%) were noted in group II (sick
      sinus syndrome in 2, hyperthyroidism in 1, and hypothyroidism in 2) and none in
      group I (0%) (P=0.03). CONCLUSIONS: RFA should be considered a first-line therapy
      even after the first episode of symptomatic AFL. There is a better long-term
      success rate, the same risk of subsequent AF, and fewer secondary effects.

PMID- 17030681
TI  - Gene transfer of a synthetic pacemaker channel into the heart: a novel strategy
      for biological pacing.
AB  - BACKGROUND: One key element of natural pacemakers is the pacemaker current
      encoded by the hyperpolarization-activated nucleotide-gated channel (HCN) gene
      family. Although HCN gene transfer has been used to engineer biological
      pacemakers, this strategy may be confounded by unpredictable consequences of
      heteromultimerization with endogenous HCN family members and limited flexibility
      with regard to frequency tuning of the engineered pacemaker. METHODS AND RESULTS:
      To circumvent these limitations, we converted a depolarization-activated
      potassium-selective channel, Kv1.4, into a hyperpolarization-activated
      nonselective channel by site-directed mutagenesis (R447N, L448A, and R453I in S4
      and G528S in the pore). Gene transfer into ventricular myocardium demonstrated
      the ability of this construct to induce pacemaker activity with spontaneous
      action potential oscillations in adult ventricular myocytes and idioventricular
      rhythms by in vivo electrocardiography. CONCLUSIONS: Given the sparse expression
      of Kv1 family channels in the human ventricle, gene transfer of a synthetic
      pacemaker channel based on the Kv1 family has novel therapeutic potential as a
      biological alternative to electronic pacemakers.

PMID- 17030682
TI  - Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented
      by aldose reductase inhibition.
AB  - BACKGROUND: Sepsis is a systemic inflammatory response syndrome characterized by
      excessive production of inflammatory cytokines and cardiovascular collapse.
      Postreceptor signaling events that lead to stress responses and cytokine
      production are sensitive to redox changes and products of lipid peroxidation.
      METHODS AND RESULTS: We tested the hypothesis that inflammatory signaling and
      cytokine generation during sepsis depend on the activity of the enzyme aldose
      reductase, which catalyzes the reduction of lipid peroxidation-derived aldehydes
      and their glutathione conjugates. The results of the present study show that
      pharmacological inhibition of aldose reductase by sorbinil or knockdown of the
      enzyme by small interfering RNA prevents the activation of nuclear factor-kappaB
      and the release of tumor necrosis factor-alpha from lipopolysaccharide-stimulated
      RAW264.7 or H9c2 cells. Increases in serum and cardiac cytokines in response to
      lipopolysaccharide challenge were suppressed by inhibition of aldose reductase.
      Treatment with sorbinil blunted the activation of protein kinase C, c-Jun NH2
      terminal kinase, and p38, as well as phosphorylation of interleukin receptor
      associated kinase, IkappaB-alpha, IkappaB kinase complex-alpha/beta, and
      phospholipase-gamma1 and -beta1. These changes were associated with decreased
      myocardial nuclear factor-kappaB and activating protein-1 activity, prostaglandin
      E2 production, induction of cyclooxygenase 2, and inducible nitric oxide
      synthase. Sorbinil treatment also induced functional recovery in myocardial
      fractional shortening in vivo and preserved contractile function of isolated
      perfused hearts. Inhibition of aldose reductase increased survival in mice
      injected with lethal doses of lipopolysaccharide. CONCLUSIONS: The present
      demonstration that aldose reductase mediates endotoxin-induced inflammation and
      cardiomyopathy suggests that inhibition of this enzyme may be useful to attenuate
      maladaptive host responses and to treat acute cardiovascular dysfunction
      associated with endotoxic shock.

PMID- 17030683
TI  - Low birth weight, a risk factor for cardiovascular diseases in later life, is
      already associated with elevated fetal glycosylated hemoglobin at birth.
AB  - BACKGROUND: It remains unclear whether the association between low birth weight
      and insulin resistance in adulthood has its origin in utero or whether it
      develops later in life depending on predisposition and exogenous factors. METHODS
      AND RESULTS: Total glycosylated hemoglobin (TGH) was quantified at delivery in
      1295 mother/child pairs serving as a surrogate of maternal and fetal glycemia.
      Multivariable regression analysis considering gestational age at delivery, the
      child's sex, maternal body mass index, and smoking during pregnancy revealed that
      an increase in TGH by 1% in the child was significantly associated with a mean
      birth weight reduction of 135 g (P<0.0001), whereas the same increase in the
      mother was associated with a mean birth weight increase of 88 g (P<0.0001). The
      ratio of fetal/maternal TGH suggests that lighter newborns have a higher
      percentage of TGH than would be expected from maternal TGH. CONCLUSIONS: The
      study demonstrates for the first time in a large population that there is an
      inverse association between TGH of a newborn and its birth weight. This might be
      due to increased insulin resistance in newborns with lower birth weight. Our data
      suggest that the pathophysiological mechanisms linking prenatal growth and
      postnatal sensitivity to insulin are present as early as before birth.

PMID- 17030684
TI  - Age- and training-dependent development of arrhythmogenic right ventricular
      cardiomyopathy in heterozygous plakoglobin-deficient mice.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
      inherited disorder that causes sudden death and right ventricular heart failure
      in the young. Clinical data suggest that competitive sports may provoke ARVC in
      susceptible persons. Genetically, loss-of-function mutations in desmosomal
      proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with
      ARVC. To test the hypothesis that reduced desmosomal protein expression causes
      ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in
      mice. METHODS AND RESULTS: Ten-month-old heterozygous plakoglobin-deficient mice
      (plakoglobin+/-) had increased right ventricular volume, reduced right
      ventricular function, and spontaneous ventricular ectopy (all P<0.05). Left
      ventricular size and function were not altered. Isolated, perfused plakoglobin+/-
      hearts had spontaneous ventricular tachycardia of right ventricular origin and
      prolonged right ventricular conduction times compared with wild-type hearts.
      Endurance training accelerated the development of right ventricular dysfunction
      and arrhythmias in plakoglobin+/- mice. Histology and electron microscopy did not
      identify right ventricular abnormalities in affected animals. CONCLUSIONS:
      Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype
      is accelerated by endurance training. This suggests a functional role for
      plakoglobin and training in the development of ARVC.

PMID- 17030686
TI  - Indications for renal arteriography at the time of coronary arteriography: a
      science advisory from the American Heart Association Committee on Diagnostic and
      Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the
      Councils on Cardiovascular Radiology and Intervention and on Kidney in
      Cardiovascular Disease.
AB  - Atherosclerotic renal artery stenosis is commonly present in patients with
      clinically manifest atherosclerosis in other vascular beds and is independently
      associated with increased cardiovascular morbidity and mortality. Screening tests
      such as renal angiography should be selectively applied to patients at high risk
      for renal artery stenosis who are potential candidates for revascularization.
      This multispecialty consensus document describes the rationale for patient
      selection for screening renal angiography at the time of cardiac catheterization.

PMID- 17030685
TI  - Pirfenidone prevents the development of a vulnerable substrate for atrial
      fibrillation in a canine model of heart failure.
AB  - BACKGROUND: Atrial fibrosis is an important substrate in atrial fibrillation
      (AF), particularly in the setting of structural heart disease. In a canine model,
      congestive heart failure (CHF) produces significant atrial fibrosis and the
      substrate for sustained AF. This atrial remodeling is a potential therapeutic
      target. The objective of the present study is to evaluate the effects of the
      antifibrotic drug pirfenidone (PFD) on arrhythmogenic atrial remodeling in a
      canine CHF model. METHODS AND RESULTS: We studied 15 canines, divided equally
      into 3 groups: control, CHF canines not treated with PFD, and CHF canines treated
      with PFD. CHF was induced by ventricular tachypacing (220 bpm for 3 weeks), and
      oral PFD was administered for the 3-week pacing period. We performed
      electrophysiology and AF vulnerability studies, atrial fibrosis measurements, and
      atrial cytokine expression studies. Only canines in the untreated CHF group
      developed sustained AF (>30 minutes, 4 of 5 canines; P<0.05). Treatment of CHF
      canines with PFD resulted in an attenuation of arrhythmogenic left atrial
      remodeling, with a significant reduction in left atrial conduction heterogeneity
      index (median [25% to 75% interquartile range] 4.96 [3.53 to 5.64] versus 2.52
      [2.11 to 2.82], P<0.01; pacing cycle length 300 ms), left atrial fibrosis (16.0%
      [13.0% to 17.5%] versus 8.7% [5.7% to 10.6%], P<0.01), and AF duration (1800
      [1020 to 1800] seconds versus 6 [5 to 22] seconds, P<0.01). Immunoblotting
      studies demonstrated the drug's effects on multiple cytokines, including a
      reduction in transforming growth factor-beta1 expression. CONCLUSIONS: Treatment
      of CHF canines with PFD results in significantly reduced arrhythmogenic atrial
      remodeling and AF vulnerability. Pharmacological therapy targeted at the fibrotic
      substrate itself may play an important role in the management of AF.

PMID- 17030687
TI  - Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by
      short-term administration of an antisense inhibitor of apolipoprotein B.
AB  - BACKGROUND: Apolipoprotein B (apoB) is an important structural component of low
      density lipoprotein cholesterol (LDL-C) and plays a key role in LDL-C transport
      and removal. Reduction in apoB synthesis is expected to reduce circulating LDL-C,
      a proven risk factor of cardiovascular disease. In the present study, we describe
      the outcome of the first-in-humans study on the safety and efficacy of an
      antisense oligonucleotide inhibitor of apoB. METHODS AND RESULTS: This study was
      a double-blind, randomized, placebo-controlled, dose-escalation investigation
      conducted at a single site in 36 volunteers with mild dyslipidemia. The study
      utilized an initial single dose of 50 to 400 mg of ISIS 301012, a 20-mer
      oligonucleotide, followed by a 4-week multiple-dosing regimen with the same
      assigned dose. Safety was assessed by the incidence, severity, and relationship
      of adverse events to dose. Efficacy was determined by changes in serum apoB and
      LDL-C relative to baseline and placebo. The most common adverse event was
      erythema at the injection site (21 of 29 subjects). ApoB was reduced by a maximum
      of 50% (P=0.002) from baseline in the 200-mg cohort. This decrease in apoB
      coincided with a maximum 35% reduction of LDL-C (P=0.001). LDL-C and apoB
      remained significantly below baseline (P<0.05) up to 3 months after the last
      dose. CONCLUSIONS: Administration of an antisense oligonucleotide to human apoB
      resulted in a significant, prolonged, and dose-dependent reduction in apoB and
      LDL-C. Although injection-site reactions were common, adherence to protocol was
      unaffected.

PMID- 17030688
TI  - Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary
      observational study.
AB  - BACKGROUND: Phosphodiesterase-5 inhibitors produce a significant decrease in
      pulmonary vascular resistance in patients with idiopathic pulmonary arterial
      hypertension. We studied the effects of tadalafil, a phosphodiesterase-5
      inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week
      period in patients of Eisenmenger syndrome having a pulmonary vascular pathology
      similar to idiopathic pulmonary arterial hypertension. METHODS AND RESULTS:
      Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25+/-8.9 years) were
      assessed hemodynamically at baseline and 90 minutes after a single dose of
      tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then
      continued daily for 12 weeks, and the patients were restudied. There was a
      significant decrease in mean pulmonary vascular resistance immediately (24.75+/
      8.49 to 19.22+/-8.23 Woods units; P<0.005) and at 12 weeks (19.22+/-8.23 to
      17.02+/-6.19 Woods units; P=0.03 versus 90 minutes). Thirteen of 16 patients
      (81.25%) showed a > or = 20% decrease in pulmonary vascular resistance and were
      defined as responders. The mean systemic oxygen saturation improved significantly
      both immediately (84.34+/-5.47% to 87.39+/-4.34%; P<0.005) and at 12 weeks
      (87.39+/-4.34% to 89.16+/-3.8%; P<0.02 versus 90 minutes) without a significant
      change in systemic vascular resistance. None of the patients had a fall in
      systemic arterial pressure, worsening of systemic oxygen saturation, or any
      adverse reactions to the drug. The mean World Health Organization functional
      class improved from 2.31+/-0.47 to 1.25+/-0.44 (P<0.0001), and the 6-minute walk
      distance improved from 344.56+/-119.06 to 387.56+/-117.18 m (P<0.001).
      CONCLUSIONS: Preliminary evaluation of tadalafil has shown efficacy and safety in
      selected patients with Eisenmenger syndrome, warranting further investigation in
      this subgroup of patients.

PMID- 17030689
TI  - Induction of macrophage chemotaxis by aortic extracts of the mgR Marfan mouse
      model and a GxxPG-containing fibrillin-1 fragment.
AB  - BACKGROUND: The primary cause of early death in untreated Marfan syndrome (MFS)
      patients is aortic dilatation and dissection. METHODS AND RESULTS: We
      investigated whether ascending aortic samples from the fibrillin-1
      underexpressing mgR mouse model for MFS or a recombinant fibrillin-1 fragment
      containing an elastin-binding protein (EBP) recognition sequence can act as
      chemotactic stimuli for macrophages. Both the aortic extracts from the mgR/mgR
      mice and the fibrillin-1 fragment significantly increased macrophage chemotaxis
      compared with extracts from wild-type mice or buffer controls. The chemotactic
      response was significantly diminished by pretreatment of macrophages with lactose
      or with the elastin-derived peptide VGVAPG and by pretreatment of samples with a
      monoclonal antibody directed against an EBP recognition sequence. Mutation of the
      EBP recognition sequence in the fibrillin-1 fragment also abolished the
      chemotactic response. These results indicate the involvement of EBP in mediating
      the effects. Additionally, investigation of macrophages in aortic specimens of
      MFS patients demonstrated macrophage infiltration in the tunica media.
      CONCLUSIONS: Our findings demonstrate that aortic extracts from mgR/mgR mice can
      stimulate macrophage chemotaxis by interaction with EBP and show that a fibrillin
      1 fragment possesses chemotactic stimulatory activity similar to that of elastin
      degradation peptides. They provide a plausible molecular mechanism for the
      inflammatory infiltrates observed in the mgR mouse model and suggest that
      inflammation may represent a component of the complex pathogenesis of MFS.

PMID- 17030690
TI  - Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular
      death in patients with carotid stenosis.
AB  - BACKGROUND: Matrix metalloproteinase-9 could exhibit an important role in the
      destabilization of atherosclerotic carotid plaques. We hypothesized that in
      patients with carotid stenosis, elevated levels of plasma matrix
      metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular
      death. METHODS AND RESULTS: We followed up 207 patients with > or = 50% carotid
      stenosis initially for a mean of 4.4 years, during which time 53 patients
      developed ipsilateral stroke or died of cardiovascular causes. The cumulative
      incidence of ipsilateral stroke or cardiovascular death was higher in those with
      matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank
      P=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard
      ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence
      interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant
      until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death
      at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and
      below the median, respectively. Elevated matrix metalloproteinase-9 and an
      echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9
      and an echorich plaque had a hazard ratio for ipsilateral stroke or
      cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of
      3.3 (95% CI, 1.1 to 9.7). CONCLUSIONS: Elevated levels of matrix
      metalloproteinase-9 in patients with > or = 50% carotid stenosis were associated
      with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining
      elevated matrix metalloproteinase-9 and plaque echolucency was associated with a
      4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for
      ipsilateral stroke.

PMID- 17030691
TI  - Cardiology patient page. The metabolic syndrome.

PMID- 17030692
TI  - Images in cardiovascular medicine. Cough cardiopulmonary resuscitation revisited.

PMID- 17030693
TI  - Images in cardiovascular medicine. Case of anomalous right superior vena cava.

PMID- 17030694
TI  - Images in cardiovascular medicine. Hiccups and dysphonic metallic voice: a unique
      presentation of Twiddler syndrome.

PMID- 17030695
TI  - Letter by Nieminen et al regarding article, "Differential impact of blood
      pressure-lowering drugs on central aortic pressure and clinical outcomes:
      principal results of the Conduit Artery Function Evaluation (CAFE) study".

PMID- 17030696
TI  - Letter by Dart et al regarding article, "Differential impact of blood pressure
      lowering drugs on central aortic pressure and clinical outcomes: principal
      results of the Conduit Artery Function Evaluation (CAFE) study".

PMID- 17030697
TI  - Letter by Cameron et al regarding article, "Differential impact of blood pressure
      lowering drugs on central aortic pressure and clinical outcomes: principal
      results of the Conduit Artery Function Evaluation (CAFE) study".

PMID- 17030698
TI  - Letter by Safar and Fournier regarding article, "Differential impact of blood
      pressure-lowering drugs on central aortic pressure and clinical outcomes:
      principal results of the Conduit Artery Function Evaluation (CAFE) study".

PMID- 17030699
TI  - Viewpoint: Heart failure and anaemia--a concept returns to the fore.

PMID- 17030701
TI  - The inflammatory hypothesis: any progress in risk stratification and therapeutic
      targets?

PMID- 17030702
TI  - Th1 adaptive immune responses in cardiac graft arteriosclerosis: deleterious or
      beneficial?

PMID- 17030703
TI  - The heart of trained athletes: cardiac remodeling and the risks of sports,
      including sudden death.

PMID- 17030704
TI  - Atrial septal defects in the adult: recent progress and overview.

PMID- 17030705
TI  - Factors predicting intraocular pressure control after phacoemulsification in
      angle-closure glaucoma.
AB  - OBJECTIVES: To investigate whether the presence of glaucomatous optic neuropathy
      affects the reduction of intraocular pressure (IOP) after phacoemulsification in
      postiridotomy eyes with primary narrow angles, and to evaluate the preoperative
      factors associated with postoperative IOP control in primary angle-closure
      glaucoma (PACG). METHODS: Patients with PACG undergoing phacoemulsification were
      prospectively enrolled and received a complete ophthalmic examination. Diurnal
      IOP was measured 1 day before and 3 months after surgery. For comparison,
      patients with primary angle closure or angle closure suspect (PAC/S) undergoing
      phacoemulsification were also enrolled. RESULTS: Postoperative reduction of IOP
      was significant in the PACG group (n = 29; P = .001) and in the PAC/S group (n =
      28; P<.001), with no significant difference between the groups. The number of
      glaucoma medications used decreased in both groups (both, P<.001). Multiple
      regression analysis for the PACG group showed that there was a positive
      correlation between postoperative IOP and preoperative factors of mean IOP (P =
      .001) and the anterior chamber depth (P = .03). CONCLUSIONS: The reduction of IOP
      3 months after phacoemulsification is significant and is similar in extent in
      postiridotomy eyes with and without glaucomatous optic neuropathy. A higher
      postoperative IOP in PACG is associated with a higher preoperative IOP and with a
      deeper preoperative anterior chamber depth.

PMID- 17030706
TI  - Novel approach for anterior chamber angle analysis: anterior chamber angle
      detection with edge measurement and identification algorithm (ACADEMIA).
AB  - OBJECTIVE: To describe a novel approach to measuring anterior chamber angle
      dimensions and configurations. METHODS: Sixty-nine images were selected randomly
      from the ultrasound biomicroscopic image database to develop the algorithm.
      Thirty images were selected for further analyses. The value of each pixel of the
      8-bit grayscale ultrasound biomicroscopic images was quantized into 0 (black) or
      1 (white), and the edge points outlining the angle were detected and fitted with
      straight lines. The dimensions and profiles of anterior chamber angles were then
      measured. RESULTS: The algorithm failed to identify the edge points correctly in
      8 (11.6%) of 69 images because of strong background noise. Three basic types of
      angle configuration were identified based on the derived angle profiles:
      constant, increasing, and decreasing, which corresponded to flat, bowed forward,
      and bowed backward iris contours, respectively. The angle measurements
      demonstrated high correlation with trabecular-iris angle and angle opening
      distance 500 (calculated as the distance from the corneal endothelium to the
      anterior iris surface perpendicular to a line drawn at 500 mum from the scleral
      spur). The strongest association was found between the averaged angle derived
      from the angle profile and the angle opening distance 500 (r = 0.91). CONCLUSION:
      The proposed algorithm has high correlations with angle opening distance and
      trabecular-iris angle with the added advantages of being fully automated,
      reproducible, and able to capture the characteristic angle configurations.
      However, good-quality ultrasound biomicroscopic images with high signal-to-noise
      ratio are required to identify the edge points correctly.

PMID- 17030707
TI  - Relative risk of progressive glaucomatous visual field loss in patients enrolled
      and not enrolled in a prospective longitudinal study.
AB  - OBJECTIVE: To establish the relative risk of progressive visual field loss in a
      sample of glaucomatous eyes enrolled in a prospective longitudinal study vs a
      matched sample of eyes not enrolled in a study. METHODS: The first visual field
      records of 66 glaucomatous eyes enrolled in a prospective longitudinal study
      (mean follow-up time, 3.4 years; mean number of visual field tests, 8.3) were
      matched to 66 eyes from patients not enrolled in a study (mean follow-up time, 3
      years; mean number of visual field tests, 3.7). Eyes were matched on the basis of
      (1) time of enrollment, (2) length of follow-up, and (3) the extent and spatial
      pattern of visual field loss. Linear regression of global visual field indexes
      was used to measure change and the relative risk of progression was calculated
      for a series of progression criteria sample. RESULTS: The relative risk of
      progressive visual field loss was on average 368% (range, 209%-673%) higher in
      the eyes not enrolled in a prospective longitudinal study. CONCLUSION: Selection
      bias may reduce the risk of progressive visual field loss in patients enrolled in
      longitudinal studies.

PMID- 17030708
TI  - Optical coherence tomography in group 2A idiopathic juxtafoveolar retinal
      telangiectasis.
AB  - OBJECTIVE: To describe the changes observed with optical coherence tomography in
      group 2A idiopathic juxtafoveolar retinal telangiectasis. METHODS: We
      retrospectively reviewed the medical records of 13 patients (25 eyes). All eyes
      underwent optical coherence tomography examination consisting of 6 radial scans,
      fundus color photography, and fluorescein angiography. We calculated retinal
      foveal and central foveal thicknesses from software mapping results. We compared
      the optical coherence tomography data with fundus photography and fluorescein
      angiography findings. RESULTS: Foveal cystoid spaces, very small or more
      prominent, were present in 20 of 25 eyes. Some degree of disruption of the inner
      segment/outer segment photoreceptor junction line was observed in 18 eyes as from
      stage 2 of idiopathic juxtafoveolar retinal telangiectasis, and intraretinal
      pigmentary proliferation was observed in 9. A foveal detachment without
      subretinal new vessels was also present in 2 eyes. Despite these abnormalities,
      central foveal thickness was below or within the range of reference values in all
      eyes; foveal thickness, in 23 of 25. In the more advanced cases, severe
      disruption of the inner segment/outer segment photoreceptor junction line and
      outer retinal atrophy were seen. CONCLUSIONS: Early in the evolution of group 2A
      idiopathic juxtafoveolar retinal telangiectasis, the optical coherence tomography
      examination disclosed intraretinal cystoid spaces without foveal thickening and
      disruption of the inner segment/outer segment photoreceptor junction line. Foveal
      thinning was present in later stages.

PMID- 17030709
TI  - Electrophysiological findings in patients with dengue-related maculopathy.
AB  - OBJECTIVE: To assess visual function in patients with dengue maculopathy using
      electrophysiological tests. METHODS: Fifteen consecutive patients with dengue
      fever who experienced vision loss between July 2004 and July 2005 were included
      in this review. Full-field electroretinograms (ERG), pattern ERGs, and multifocal
      ERGs were performed. RESULTS: The most common electrophysiological finding (60%,
      9/15) was a normal or mildly abnormal full-field ERG with reduced pattern ERG P50
      amplitude and abnormal mfERG. Typically, multifocal ERG demonstrated a focal area
      of decreased macular response (especially between the fovea and optic nerve).
      Pattern ERG suggested normal optic nerve function in all but 1 case. Four
      patients had more severely reduced full-field ERG responses with reduced a-wave
      amplitude (suggestive of photoreceptor dysfunction), 3 of whom had an
      electronegative maximal response (suggestive of additional postreceptor
      dysfunction). Repeat multifocal ERG showed little change in 7 patients and
      incomplete resolution in 2 patients over 3 to 10 months. CONCLUSION: Retinal
      dysfunction associated with dengue maculopathy was localized mainly around the
      foveal region. It appeared to affect the outer and middle retina more severely
      with relative sparing of the inner retina. Retinal dysfunction may persist for
      several months. Longer follow-up is required to determine whether these changes
      are permanent.

PMID- 17030710
TI  - Vascular endothelial growth factor a in eyes with uveal melanoma.
AB  - OBJECTIVES: To determine the presence of vascular endothelial growth factor A
      (VEGF-A) in the aqueous humor of eyes with uveal melanoma and to identify its
      source. METHODS: The VEGF-A concentrations were determined in aqueous humor
      samples obtained after enucleation from 74 eyes with untreated uveal melanoma and
      from 8 eyes with treated uveal melanoma. Patient survival and clinical and
      histopathological tumor variables were compared. In situ hybridization, Western
      blot analysis, and enzyme-linked immunosorbent assay were used to determine
      expression of VEGF-A in tumor tissue and in overlying retina. RESULTS: Aqueous
      VEGF-A concentrations ranged from 18 to 826 pg/mL in 74 untreated eyes, while
      concentrations in 30 control eyes were significantly lower (median, 50.1 pg/mL)
      (P<.001). Concentrations in 8 treated eyes were much higher (median, 364 pg/mL).
      In situ hybridization on tissue sections and Western blot analysis and enzyme
      linked immunosorbent assay on tissue extracts revealed VEGF-A in uveal melanoma
      tissue and in retinal tissue. CONCLUSIONS: Uveal melanoma is associated with
      increased concentrations of VEGF-A in aqueous humor. Aqueous VEGF-A concentration
      correlates with largest basal tumor diameter and with the tumor height. In eyes
      with uveal melanoma, tumor and retinal tissues are sources of VEGF-A.

PMID- 17030711
TI  - Amniotic membrane transplantation in children with symblepharon and massive
      pannus.
AB  - OBJECTIVE: To report our pediatric experience with amniotic membrane
      transplantation for ocular surface and forniceal reconstruction. METHODS:
      Retrospective case review of children who underwent superficial keratectomy,
      symblepharon lysis, and forniceal reconstruction using amniotic membrane
      transplantation. The underlying diagnosis, visual acuity, level of discomfort at
      first and last visits, and surgical details were noted. RESULTS: Four patients (5
      eyes) were included. Two patients had epidermolysis bullosa (1 recessive
      dystrophic and 1 junctional), 1 had laryngo-onychocutaneous syndrome, and 1 had
      measles-related keratitis and was positive for human immunodeficiency virus.
      Their mean age when initially seen was 8.7 years (age range, 4-16 years), and
      mean follow-up was 18.25 months (range, 12-29 months). The mean visual acuity
      preoperatively was 1.1 logMAR (logarithm of the minimum angle of resolution)
      (range, 1-1.3), and postoperatively was 0.7 (range, 0.2-1.2). All patients
      experienced increased ocular comfort with anatomical restoration of corneal and
      conjunctival surfaces. Visual acuity improved in 3 eyes. Only the patient with
      laryngo-onychocutaneous syndrome had recurrence of granuloma, at 9 months after
      surgery. CONCLUSION: Amniotic membrane transplantation with symblepharon lysis is
      effective for ocular surface reconstruction in the management of epidermolysis
      bullosa and other conditions that cause corneal scarring and symblepharon in
      children. In this small series, children with epidermolysis bullosa fared better
      and the effects of surgery lasted longer compared with patients with other causes
      of symblepharon and massive pannus.

PMID- 17030712
TI  - Bioengineered human corneal endothelium for transplantation.
AB  - OBJECTIVE: To investigate whether the bioengineered human corneal endothelial
      cell (HCEC) monolayers harvested from thermoresponsive culture supports could be
      used as biological tissue equivalents. METHODS: Untransformed adult HCECs derived
      from eye bank corneas were cultivated on a thermoresponsive poly-N
      isopropylacrylamide-grafted surface for 3 weeks at 37 degrees C. Confluent cell
      cultures with a phenotype and cell density similar to HCECs in vivo were detached
      as a laminated sheet by lowering the culture temperature to 20 degrees C. In
      vitro characteristics of the HCEC sheets were determined evaluating their
      viability and by scanning electron microscopy, immunohistochemistry, and
      histological studies. RESULTS: After separation from culture surfaces via a
      thermal stimulus, the HCEC sheets remained viable. Polygonal cell morphology and
      multiple cellular interconnections were observed throughout the HCEC sheets.
      Immunolocalization of zonula occludens-1 and Na+,K+-adenosine triphosphatase
      (ATPase) indicated the formation of tight junctions and the distribution of ionic
      pumps at the cell boundary. In addition, we ascertained that cultured HCECs have
      a monolayered architecture that mimics native corneal endothelium. CONCLUSION:
      These data suggest that a well-organized and functional HCEC monolayer can
      feasibly be used as tissue equivalents for replacing compromised
      endothelium.Clinical Relevance Bioengineered human corneal endothelium fabricated
      from thermoresponsive supports can potentially offer a new therapeutic strategy
      for corneal endothelial cell loss.

PMID- 17030713
TI  - Altered tear composition in smokers and patients with graves ophthalmopathy.
AB  - OBJECTIVES: To analyze, compare, and contrast tear composition in healthy
      nonsmokers, smokers who were otherwise healthy, and patients with Graves disease
      (GD) accompanied by Graves ophthalmopathy (GO) of varying severity. METHODS:
      Reflex tears were collected using Schirmer strips from 37 healthy nonsmokers, 33
      otherwise healthy smokers, 51 patients with GD, and 85 patients with GO.
      Thyrotropin receptor-stimulating activity and serum thyroid-stimulating
      antibodies were measured. Pooled tear samples from healthy nonsmokers, healthy
      smokers, and patients with GO were separated by means of electrophoresis.
      Proteins expressed in healthy smokers, patients with GO, and healthy nonsmokers
      were separated by means of electrophoresis and analyzed by mass spectrometry.
      RESULTS: Based on the 97th percentile of findings from healthy nonsmokers,
      specific thyrotropin receptor-stimulating activity was detected in 25% of the
      tear samples from healthy smokers, 32% of those from patients with GD, and 41% of
      those from patients with GO. Clinical activity scores correlated with serum
      thyroid-stimulating antibody levels but not tear thyrotropin receptor-stimulating
      activity. Electrophoresis revealed additional proteins of 30 to 41 kDa in the
      tear samples from patients with GO and healthy smokers compared with samples from
      healthy nonsmokers. These proteins were identified as zinc-alpha2-glycoprotein
      and lactoferrin but have no thyrotropin receptor-stimulating activity.
      CONCLUSIONS: We demonstrate similar changes in tear composition in patients with
      GO and healthy smokers compared with healthy nonsmokers. Expression of zinc
      alpha2-glycoprotein and lactoferrin is increased and their molecular weights are
      modified, suggesting degradation and/or changes during glycosylation, which may
      affect the bioactivities of zinc-alpha2-glycoprotein and lactoferrin. Clinical
      Relevance Smoking, which is a significant risk factor for the development of GO,
      modifies tear composition.

PMID- 17030714
TI  - Association of connective tissue growth factor with fibrosis in vitreoretinal
      disorders in the human eye.
AB  - OBJECTIVE: To investigate the expression of the profibrotic connective tissue
      growth factor (CTGF) in relation to severity of intraocular fibrosis and
      neovascularization in human vitreoretinal disorders for the identification of
      potential therapeutic targets to prevent fibrosis. METHODS: Concentrations of
      CTGF were measured by enzyme-linked immunosorbent assay in 119 vitreous samples
      from patients with proliferative diabetic retinopathy, proliferative
      vitreoretinopathy, epiretinal membrane, and macular hole. Clinical data,
      including degree of intraocular fibrosis and neovascularization, were collected
      using standardized forms. RESULTS: Multifactorial analysis revealed that only
      CTGF levels correlated highly significantly with degree of fibrosis in the
      various vitreoretinal disorders studied (P<.001; R2= 47.7%). Likewise, variation
      in degree of fibrosis was best predicted by CTGF levels (P<.001). CONCLUSION: The
      strong correlation between CTGF levels and degree of fibrosis in vitreoretinal
      disorders suggests that CTGF is an important factor in ocular fibrosis, similar
      to its role in pathologic fibrosis in other organs. CLINICAL RELEVANCE:
      Connective tissue growth factor may be a therapeutic target for prevention of
      sight-threatening vitreoretinal scarring in the eye.

PMID- 17030715
TI  - Association between vision and hearing impairments and their combined effects on
      quality of life.
AB  - OBJECTIVES: To assess associations between age-related vision and hearing
      impairments and whether combined sensory losses magnify effects on health-related
      quality of life. METHODS: Seventy-five percent of survivors (n = 2334) were
      reexamined at Blue Mountains Eye Study 5-year examinations and 86.3% (2015)
      attended hearing assessments. Visual impairment was defined as visual acuity less
      than 20/40 (better eye), and hearing impairment as average pure-tone air
      conduction threshold greater than 25 dB (500-4000 Hz, better ear). RESULTS:
      Persons with visual impairment, compared with those without visual impairment,
      had lower mean audiometric thresholds across all frequencies (P< or =.05). For
      each 1-line (5-letter) reduction in best-corrected visual acuity and presenting
      visual acuity, hearing loss prevalence increased by 18% and 13%, respectively.
      Cataract and age-related maculopathy were also associated with hearing loss
      (respectively, multivariate-adjusted odds ratio, 1.3 and 1.6; 95% confidence
      interval, 1.0-1.7 and 1.1-3.1). The association between age-related maculopathy
      and hearing loss was stronger at younger ages (<70 years). Combined impairments
      were associated with poorer health-related quality of life than were single
      impairments (multivariate-adjusted 36-Item Short-Form Health Survey mean physical
      and mental component scores; Ptrend = .001 and <.001, respectively). CONCLUSIONS:
      Older persons with visual impairment were also more likely to have hearing loss
      in this study, which suggests that these sensory impairments could share common
      risk factors or biologic aging markers. Combined sensory impairments also
      cumulatively affect health-related quality of life.

PMID- 17030716
TI  - Effect of medical therapy on glaucoma filtration surgery rates in Ontario.
AB  - OBJECTIVE: To analyze trends of glaucoma filtration surgery in Ontario. METHODS:
      From April 1, 1992, through March 31, 2004, correlations were examined between
      the annual rates of trabeculectomies in Ontario, the use of glaucoma medications,
      and the numbers of practicing ophthalmologists and optometrists. RESULTS: The
      number of trabeculectomies per 1000 persons at risk for primary open-angle
      glaucoma increased from 33.5 in 1992 to 46.2 in 1996 (37.7% increase; 6.6%
      increase per year) and then steadily decreased to 38.2 in 2004 (17.0% decrease;
      2.7% decrease per year). The number of glaucoma medications dispensed in Ontario
      increased from 766 000 in 1992 to 1 466 543 in 2004 (91.5% increase; 10.5% annual
      increase). The increase in dispensed prostaglandin analogues strongly correlated
      (P<.001; 95% confidence interval, -0.87 to -0.41) with the decreasing number of
      trabeculectomies. The decreasing number of ophthalmologists positively correlated
      (r = 0.87) with the filtration surgery rate after 1997. CONCLUSIONS: The number
      of trabeculectomies has decreased substantially in Ontario coinciding with the
      introduction of medications for the treatment of glaucoma in December 1996. This
      decrease in trabeculectomies highly correlated with the introduction of
      prostaglandin analogues (P<.001) and the decreasing number of ophthalmologists
      from 1997 through 2004.

PMID- 17030717
TI  - What we don't know about avastin might hurt us.

PMID- 17030719
TI  - Ophthalmology in Venezuela.

PMID- 17030718
TI  - Ophthalmology from ancient Persia to the modern era.

PMID- 17030720
TI  - Histopathology and ultrastructure of human corneas after amniotic membrane
      transplantation.

PMID- 17030721
TI  - Presenile cataract: consider cholestanol.

PMID- 17030722
TI  - Familial retinal arterial tortuosity associated with tortuosity in nail bed
      capillaries.

PMID- 17030723
TI  - Congenital iris ectropion and glaucoma associated with intestinal neuronal
      dysplasia: a manifestation of a neural crest syndrome.

PMID- 17030724
TI  - Iris ectopic thyroid tissue: report of a case.

PMID- 17030725
TI  - Ligneous conjunctivitis in a Mexican patient with a mutation in the plasminogen
      (PLG) gene.

PMID- 17030726
TI  - Melioidosis with endophthalmitis.

PMID- 17030727
TI  - Delayed Nd:YAG laser membranotomy for traumatic premacular hemorrhage.

PMID- 17030728
TI  - A transilluminating scleral lesion.

PMID- 17030729
TI  - Optimizing the use of tumor necrosis factoralpha inhibitors in refractory
      uveitis.

PMID- 17030730
TI  - Intravitreal triamcinolone in diabetic macular edema.

PMID- 17030731
TI  - Optic nerve structure in healthy subjects.

PMID- 17030732
TI  - Acute respiratory distress due to verteporfin infusion for photodynamic therapy.

PMID- 17030733
TI  - Risk of Lasik surgery vs contact lenses.

PMID- 17030734
TI  - The eyes and brain of Johann Sebastian Bach.

PMID- 17030735
TI  - DDD mice, a novel acute mouse model of Parkinson's disease.
AB  - We describe the development of a novel animal model of acute severe dopamine (DA)
      deficiency by using genetically altered mice lacking the DA transporter (DAT-KO
      mice). In the absence of a DAT-mediated recycling mechanism in these mice,
      striatal DA concentrations become entirely dependent on its de novo synthesis,
      and acute pharmacologic inhibition of tyrosine hydroxylase induces transient (up
      to 16 hours) elimination of brain DA. Dopamine-deficient DAT-KO mice (DDD mice)
      demonstrate a striking behavioral phenotype manifested as severe akinesia,
      rigidity, tremor, and ptosis. We propose that DDD mice represent a novel acute
      model of severe DA deficiency that might be used to identify compounds with
      potential therapeutic use for the treatment of Parkinson's disease (PD). This
      model is particularly promising as a tool for evaluating the efficacy of
      compounds that may induce movement independently of DA. The advantages and
      limitations of DDD mice in comparison to other rodent PD models are discussed.

PMID- 17030736
TI  - Safinamide: from molecular targets to a new anti-Parkinson drug.
AB  - Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and
      slowing disease progression. Of all remedies, levodopa remains the most effective
      for symptomatic relief, but the medical need for neuroprotectant drugs is still
      unfulfilled. Safinamide, currently in phase III clinical trials for the treatment
      of PD, is a unique molecule with multiple mechanisms of action and a very high
      therapeutic index. It combines potent, selective, and reversible inhibition of
      MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of
      glutamate release. Safinamide has neuroprotective and neurorescuing effects in
      MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model.
      Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted
      mice and reverses the waning motor response after prolonged levodopa treatment in
      6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics,
      and is suitable for once-a-day administration. Therefore, safinamide may be used
      in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to
      test disease-modifying potential.

PMID- 17030737
TI  - Symptom relief in Parkinson disease by safinamide: Biochemical and clinical
      evidence of efficacy beyond MAO-B inhibition.
AB  - In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day,
      higher than previously tested) were administered to 13 parkinsonian patients
      along with a stable dose of dopamine (DA) agonist, causing a significant
      progressive improvement in motor performance as evaluated by the Unified
      Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2
      points; P < 0.001). In association with levodopa, the same doses of safinamide in
      another group of patients (N = 11) induced a significant decrease in motor
      fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose
      proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B
      was fully inhibited (95%) at all doses tested, we suggest that these biochemical
      and symptomatic dose-dependent effects must be related to additional mechanisms
      of action, such as inhibition of glutamate release, increased dopamine release,
      or inhibition of dopamine re-uptake. These hypotheses are under investigation and
      will pursue confirmation in controlled clinical trials.

PMID- 17030738
TI  - New pharmacologic horizons in the treatment of Parkinson disease.
AB  - Many of the motoric features that define Parkinson's disease (PD) result
      primarily from the loss of dopaminergic neurons of the substantia nigra. l-dopa
      remains at present the most powerful symptomatic drug for the treatment of this
      condition. However, motor complications of chronic l-dopa treatment have emerged
      as a major limitation of this therapy. Slowing or delaying the progression of the
      disease with neuroprotective therapies may delay the need for l-dopa. In the past
      few years, novel insight into the pathogenetic mechanisms of neurodegeneration in
      PD has been provided. Mitochondrial function deficiency, increased oxidative
      stress, apoptosis, excitotoxicity, and inflammation are part of the processes
      that ultimately result in neurodegeneration. Drugs that are now under clinical
      scrutiny as neuroprotectant include molecules that combine one or more of the
      following properties: (1) monoamine oxidase inhibition (rasagiline, safinamide);
      (2) mitochondrial enhancement (coenzyme Q10, creatine); (3) antiapoptotic
      activity; (4) anti-inflammatory activity; (5) protein aggregation inhibition; (6)
      neurotrophic activity. In advanced Parkinson's disease, the combination of
      disease progression and l-dopa therapy leads to the development of motor response
      complications, particularly wearing off, on off, dyskinesias and dystonias. The
      nonphysiologic pulsatile stimulation of striatal dopamine receptors, produced by
      the currently available dopaminergic drugs, may trigger a dysregulation of many
      neurotransmitter systems within the basal ganglia, mainly localized on medium
      spiny striatal neurons. These include alterations of glutamatergic, serotonergic,
      adrenergic and adenosine A(2A) receptors. Novel strategies for pharmacological
      intervention with nondopaminergic treatments hold the promise of providing
      effective control or reversal of motor response complications. Of particular
      interest are NMDA and AMPA antagonists or drugs acting on 5-HT subtype 2A, alpha2
      adrenergic, and adenosine A(2) receptors. Future strategies may also target pre-
      and postsynaptic components that regulate firing pattern of basal ganglia
      neurons, such as synaptic vesicle proteins, nonsynaptic gap junction
      communication mechanisms, or signal transduction systems that modulate the
      phosphorylation state of glutamatergic receptors.

PMID- 17030739
TI  - Structure of the human mitochondrial monoamine oxidase B: new chemical
      implications for neuroprotectant drug design.
AB  - Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound flavoenzyme
      that is a well-known target for antidepressant and neuroprotective drugs. The 3A
      resolution structure of recombinant human MAO-B originally determined was of the
      enzyme complexed with pargyline, an irreversible inhibitor covalently bound to
      the N5 atom of the flavin coenzyme. The crystal structure shows that the enzyme
      is dimeric. Each monomer binds to the membrane via a C-terminal transmembrane
      helix and by apolar loops located at various positions in the sequence. Substrate
      binding to the enzyme involves negotiating a loop covering a 290A3 entrance
      apolar cavity before reaching an apolar 420A3 substrate cavity where the flavin
      coenzyme is located. The 1.7A isatin-MAO-B structure allowed a detailed
      examination of the enzyme's active site. A novel specific reversible MAO-B
      inhibitor, which is found as a contaminant in polystyrene plastics (1,4-diphenyl
      2-butene), binds in both the entrance and the substrate cavity. Analogous MAO-B
      specific inhibitors that bind in a manner traversing both cavities include trans
      trans farnesol and chlorostyrylcaffeine. The rotation of the Ile199 side chain to
      an "open" conformation plays an essential role in this specificity. These results
      form a molecular basis for the design of new human MAO-B-specific reversible
      inhibitors.

PMID- 17030740
TI  - A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.
AB  - In many parkinsonian syndromes, neuromelanin (NM)-containing dopaminergic neurons
      of the substantia nigra (SN) are selectively targeted by the noxius pathogens.
      Studies of the constitutional and functional features of human NM allow the
      formulation of a logical hypothesis on its role in parkinsonian syndromes. In the
      early stages, NM synthesis and iron-chelating properties may act as a powerful
      protective mechanism, delaying symptom appearance and/or slowing disease
      progression. Once these systems have been exhausted, the pathogenic mechanisms
      affecting cytoplasmic organelles other than NM destroy NM-harboring neurons, with
      consequent pouring out of NM granules. These in turn activate microglia, causing
      release of nitric oxide, interleukin-6 and tumor necrosis factor-alpha, thus
      becoming an important determinant of disease aggravation. Neuromelanin appears to
      be a suitable target for devising chemical agents that might modify the course of
      these diseases.

PMID- 17030741
TI  - A "nerve" ending story in the identification of mutations in Charcot-Marie-Tooth
      neuropathy.

PMID- 17030742
TI  - Gabapentin in the operating room: clear for discharge?

PMID- 17030743
TI  - Repetitive and impulsive behaviors in treated Parkinson disease.

PMID- 17030745
TI  - Risk of ischemic complications related to the intensity of triptan and ergotamine
      use.
AB  - OBJECTIVE: To investigate whether the intensity of triptan and ergotamine use, in
      specific overuse, is associated with the risk of ischemic complications. METHODS:
      We conducted a retrospective nested case-control study using data from the PHARMO
      Record Linkage System. All patients with more than one prescription for either a
      triptan or ergotamine were initially identified. Cases were all patients who were
      admitted to the hospital for an ischemic complication. Matched controls were
      assigned the same index date as the cases. The determinant was the intensity of
      use of triptans and ergotamine during 1 year preceding the index date. Overuse
      was defined as use of > or =90 defined daily doses during that year. Conditional
      logistic regression was used to estimate odds ratios (ORs), adjusting for
      confounders. Stratified analysis was used to estimate the risk for both patients
      using and those not using cardiovascular drugs. RESULTS: A total of 17,439
      patients received more than one prescription. A total of 188 cases and 689
      controls were identified. Triptan overuse was not associated with an increased
      risk of ischemic complications (OR 0.96; 95% CI: 0.49 to 1.90). Overuse of
      triptans in patients concomitantly using cardiovascular drugs did not increase
      this risk. Overuse of ergotamine turned out to be a risk factor for ischemic
      complications (OR 2.55; 95% CI: 1.22 to 5.36). Patients overusing ergotamine and
      concomitantly using cardiovascular drugs were at highest risk (OR 8.52; 95% CI
      2.57 to 28.2). CONCLUSIONS: In general practice, triptan overuse does not
      increase the risk of ischemic complications. Overuse of ergotamine may increase
      the risk of these complications, especially in those simultaneously using
      cardiovascular drugs.

PMID- 17030744
TI  - Treatment of neurocysticercosis: current status and future research needs.
AB  - Here we put forward a roadmap that summarizes important questions that need to be
      answered to determine more effective and safer treatments. A key concept in
      management of neurocysticercosis is the understanding that infection and disease
      due to neurocysticercosis are variable and thus different clinical approaches and
      treatments are required. Despite recent advances, treatments remain either
      suboptimal or based on poorly controlled or anecdotal experience. A better
      understanding of basic pathophysiologic mechanisms including parasite survival
      and evolution, nature of the inflammatory response, and the genesis of seizures,
      epilepsy, and mechanisms of anthelmintic action should lead to improved
      therapies.

PMID- 17030746
TI  - Skin biopsies demonstrate MPZ splicing abnormalities in Charcot-Marie-Tooth
      neuropathy 1B.
AB  - OBJECTIVE: To demonstrate that intronic mutations in the myelin protein zero
      (MPZ) cause Charcot-Marie-Tooth neuropathy 1B (CMT1B) by disrupting MPZ splicing.
      METHODS: We report a family with a T>G transversion at the invariant + 2 position
      in intron 4 of MPZ (c.614 + 2T>G) that abolishes 5' donor site recognition and is
      predicted to alter MPZ splicing. We obtained detailed clinical and
      neurophysiologic analysis of the family. We performed skin biopsies to
      investigate splicing abnormalities, MPZ protein levels, and localization in
      myelinated nerves. RESULTS: Patients developed a late onset neuropathy with
      minimally slow nerve conduction velocities. Skin biopsies confirmed the predicted
      skipping of exon 4 and downstream frameshift of the mutant MPZ. Quantitative
      immuno-EM demonstrated normal nerve MPZ levels, suggesting that the mutant MPZ
      was transported to compact myelin. CONCLUSIONS: Intronic mutations cause CMT1B by
      disrupting splicing and certain MPZ mutations may cause neuropathy by interacting
      with the wild type MPZ in the extracellular space of compact myelin.

PMID- 17030747
TI  - Posttraumatic cerebral infarction in patients with moderate or severe head
      trauma.
AB  - OBJECTIVE: To evaluate the frequency, types, and location of posttraumatic
      cerebral infarction, to assess if secondary cerebral insults were associated with
      cerebral infarction, and to determine if cerebral infarction affected patients'
      outcome. METHODS: We based diagnosis of cerebral infarction on review of brain CT
      scans. We assessed frequency of secondary cerebral insults, including
      intracranial hypertension, cerebral hypoperfusion, systolic hypo- and
      hypertension, arterial blood oxygen desaturation, hypocapnia, and hyperthermia,
      using clinical charts. We used the Glasgow Outcome Scale to evaluate outcome at 6
      months after trauma. RESULTS: Of the 89 patients included, a total of 28 cerebral
      infarctions were found in 17 cases (19.1%). Infarctions were territorial in 23
      (82.1%) and watershed in 5 (17.9%) cases. Territorial infarctions were localized
      to the middle cerebral artery (n = 9, 32.1%), lenticulostriate arteries (n = 6,
      21.4%), posterior cerebral artery (n = 3, 10.7%), anterior cerebral artery (n =
      3, 10.7%), thalamoperforating arteries (n = 1, 3.6%), and basilar artery (n = 1,
      3.6%) territories. Watershed infarctions were in the boundary (n = 4, 14.3%) and
      terminal (n = 1, 3.6%) zones. Intracranial hypertension was the only independent
      variable predicting cerebral infarction (odds ratio [OR] 13.3; 95% CI 2.8 to
      62.6). At 6 months after trauma, there was a lower proportion of patients with
      good outcome among patients with cerebral infarction vs patients without (23.5
      and 61.1%; p = 0.005). Cerebral infarction was the only independent predictor of
      6-month outcome (OR of good outcome 0.19, 95% CI 0.06 to 0.66). CONCLUSIONS: The
      risk of developing posttraumatic cerebral infarction may be higher in patients
      with intracranial hypertension than in those without. Patients with posttraumatic
      cerebral infarction may be at increased risk of residual disability.

PMID- 17030748
TI  - Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic
      stroke.
AB  - BACKGROUND: Hemorrhagic transformation (HT) after cerebral ischemia seems to be
      related to the endothelial disruption secondary to the ischemic process.
      Albuminuria has recently been found to be a marker of chronic endothelial damage.
      OBJECTIVE: To investigate the relationship between albuminuria and HT in patients
      with acute ischemic stroke. METHODS: We studied 200 patients (51.5% men, age 72.5
      +/- 8.5 years) with ischemic stroke within the first 24 hours of evolution. HT
      development was assessed on CT performed between days 4 and 7 of evolution and
      classified according to the ECASS II criteria. Urinary samples were collected
      within the first 3 hours after admission and the presence of albuminuria, which
      was considered to be present when the ratio albumin-to-creatinine was > or =30
      mg/g creatinine, was determined by nephelometry within the first 24 hours of
      evolution. RESULTS: Forty-nine patients (24.5%) had albuminuria and 36 (18%) had
      HT on the second CT scan. After adjusting for potential confounders including a
      previous history of diabetes mellitus, hypertension and atrial fibrillation,
      stroke severity, the presence of early signs of ischemia and leukoaraiosis on the
      baseline CT scan, and IV anticoagulant treatment, logistic regression analysis
      showed that albuminuria was independently associated with HT (OR, 7.45; 95% CI
      2.30 to 24.16). Moreover, albuminuria was also a significant and independent
      predictor of parenchymal hemorrhage type 1 and 2 (OR, 8.30; 95% CI 1.77 to
      38.89). CONCLUSION: Albuminuria is an independent predictor of hemorrhagic
      transformation, and particularly of the most severe bleedings, in patients with
      acute ischemic stroke. Due to the small number of events, the predictive capacity
      of albuminuria should be confirmed in larger studies.

PMID- 17030749
TI  - Cerebellar infarction presenting isolated vertigo: frequency and vascular
      topographical patterns.
AB  - OBJECTIVE: To determine the frequency of cerebellar infarction mimicking
      vestibular neuritis (VN), the pattern of clinical presentation, and the territory
      of the cerebellar infarction when it simulates VN. METHODS: We studied 240
      consecutive cases of isolated cerebellar infarction in the territories of the
      cerebellar arteries diagnosed by brain MRI from the acute stroke registry at the
      Keimyung University Dongsan Medical Center. RESULTS: We identified 25 patients
      (10.4%) with isolated cerebellar infarction who had clinical features suggesting
      VN. Two types of cerebellar infarction simulating VN were found: isolated
      spontaneous prolonged vertigo with imbalance as a sole manifestation of
      cerebellar infarction (n = 24) and isolated spontaneous prolonged vertigo with
      imbalance as an initial manifestation of cerebellar infarction (n = 1) followed
      by delayed neurologic deficits 2 days after the onset. The cerebellar infarction
      territory most commonly involved was the medial branch of the posterior inferior
      cerebellar artery territory (24/25: 96%), followed by the anterior inferior
      cerebellar artery territory (1/25: 4%). None of patients with infarcts in the
      territory of the superior cerebellar artery or multiple cerebellar arteries
      showed isolated spontaneous prolonged vertigo. CONCLUSIONS: Cerebellar infarction
      simulating vestibular neuritis is more common than previously thought. Early
      recognition of the pseudo-vestibular neuritis of vascular cause may allow
      specific management.

PMID- 17030750
TI  - Association of aortic plaque with intracranial atherosclerosis in patients with
      stroke.
AB  - OBJECTIVE: To determine whether there is a relationship between aortic plaques
      and intracranial (IC) atherosclerosis. METHODS: We reviewed 922 patients with
      stroke who had both transesophageal echocardiography and cerebral angiography.
      The plaques of these patients were classified as either complex aortic plaques
      (CAP), which protruded > or =4 mm or were present as mobile lesions in the
      proximal aorta, or simple aortic plaques (SAP), which were <4 mm or present in
      the descending aorta. Cerebral artery atherosclerosis was classified as either an
      IC or extracranial (EC) atherosclerosis. RESULTS: Among the 922 patients, we
      found aortic plaques in 237 patients (26%). There were 111 (47%) patients of SAP,
      74 (31%) patients with CAP, and 52 (22%) patients that had both SAP and CAP.
      Angiography showed IC or EC atherosclerosis in 511 patients (55%). The presence
      of aortic plaques was significantly associated with IC or EC atherosclerosis. The
      significance appeared to be due to the strong association between the presence of
      SAP and IC atherosclerosis (51% SAP vs 35% no plaques; odds ratio = 1.94, 95% CI:
      1.17 to 3.21). In the multiple logistic regression analysis, SAP were independent
      predictors of IC atherosclerosis CONCLUSIONS: The presence of simple aortic
      plaques may be a marker of advanced vascular disease. Detection of simple aortic
      plaques during transesophageal echocardiography may have clinical implications
      because patients with these plaques frequently had concomitant intracranial
      atherosclerosis, a risk factor for stroke.

PMID- 17030751
TI  - The Motor Activity Log-28: assessing daily use of the hemiparetic arm after
      stroke.
AB  - BACKGROUND: Data from monkeys with deafferented forelimbs and humans after stroke
      indicate that tests of the motor capacity of impaired extremities can
      overestimate their spontaneous use. Before the Motor Activity Log (MAL) was
      developed, no instruments assessed spontaneous use of a hemiparetic arm outside
      the treatment setting. OBJECTIVE: To study the MAL's reliability and validity for
      assessing real-world quality of movement (QOM scale) and amount of use (AOU
      scale) of the hemiparetic arm in stroke survivors. METHODS: Participants in a
      multisite clinical trial completed a 30-item MAL before and after treatment (n =
      106) or an equivalent no-treatment period (n = 116). Participants also completed
      the Stroke Impact Scale (SIS) and wore accelerometers that monitored arm movement
      for three consecutive days outside the laboratory. All were 3 to 12 months post
      stroke and had mild to moderate paresis of an upper extremity. RESULTS: After an
      item analysis, two MAL tasks were eliminated. Revised participant MAL QOM scores
      were reliable (r =0.82). Validity was also supported. During the first
      observation period, the correlation between QOM and SIS Hand Function scale
      scores was 0.72. The corresponding correlation for QOM and accelerometry values
      was 0.52. Participant QOM and AOU scores were highly correlated (r = 0.92).
      CONCLUSIONS: The participant Motor Activity Log is reliable and valid in
      individuals with subacute stroke. It might be employed to assess the real-world
      effects of upper extremity neurorehabilitation and detect deficits in spontaneous
      use of the hemiparetic arm in daily life.

PMID- 17030752
TI  - Physical fitness and lifetime cognitive change.
AB  - OBJECTIVE: To test the hypothesis that physical fitness is associated with more
      successful cognitive aging. METHODS: Surviving participants (N = 460) of the
      Scottish Mental Survey of 1932 were tested on the same general cognitive test at
      age 11 and 79 years. Measures of grip strength, 6-meter walk time, and lung
      function (forced expiratory volume from the lungs in 1 second [FEV1]) were
      assessed at age 79 years. RESULTS: A latent physical fitness trait, derived by
      principal components analysis of the three fitness measures, was significantly
      associated with successful cognitive aging. Cognitive score at age 11, sex,
      social class, and APOE-epsilon4 genotype were included as covariables. Higher
      childhood IQ was associated with better lung function in old age. CONCLUSIONS:
      Physical fitness is associated with cognitive reserve. Intervention studies aimed
      at making older people fitter are good candidates to improve cognitive aging.

PMID- 17030753
TI  - Ten-year risk of dementia in subjects with mild cognitive impairment.
AB  - OBJECTIVE: To investigate the 10-year risk of dementia in subjects with mild
      cognitive impairment (MCI) ages 40 to 85 years. METHODS: We selected subjects
      from a memory clinic if they met one of the following definitions of MCI:
      cognitive complaints (n = 181), aging-associated cognitive decline (AACD) (n =
      163), mild functional impairment (n = 86), or amnestic MCI (n = 64). Subjects
      were reassessed after 2, 5, and 10 years. The risk of dementia was calculated
      with Kaplan-Meier statistics. Analyses were conducted in the entire sample and in
      subgroups of subjects aged 40 to 54 years, 55 to 69 years, and 70 to 85 years.
      RESULTS: The 10-year risk of dementia was 0.27 (95% CI 0.20 to 0.34) in subjects
      with cognitive complaints, 0.28 (95% CI 0.21 to 0.35) in subjects with AACD, 0.44
      (95% CI 0.32 to 0.56) in subjects with mild functional impairment, and 0.48 (95%
      CI 0.35 to 0.61) in subjects with amnestic MCI. Ninety-one percent of the
      demented subjects had probable AD. The risk of dementia increased with increasing
      age for all MCI definitions (p < 0.001). Depending on the MCI definition used,
      the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years, from
      0.37 to 0.52 in subjects aged 55 to 69 years, and from 0.77 to 1.0 in subjects
      aged 70 to 85 years. CONCLUSIONS: The majority of subjects with MCI do not
      progress to dementia at the long term. Age strongly influences the dementia risk.
      MCI often represents the predementia stage of a neurodegenerative disorder in
      elderly subjects but rarely in younger subjects.

PMID- 17030754
TI  - Relation between body mass index and cognitive function in healthy middle-aged
      men and women.
AB  - OBJECTIVE: To assess whether body mass index (BMI) is associated with cognitive
      function and cognitive decline in healthy men and women. METHODS: In this
      prospective cohort study, we analyzed data from 2,223 healthy workers aged 32 to
      62 years at baseline. Medical, psychosocial, and environmental data were
      collected in 1996 and in 2001. We tested cognitive functions at baseline and at
      follow-up with word-list learning (four recalls), a Digit-Symbol Substitution
      Test, and a selective attention test. RESULTS: Cross-sectionally, a higher BMI
      was associated with lower cognitive scores after adjustment for age, sex,
      educational level, blood pressure, diabetes, and other psychosocial covariables.
      A higher BMI at baseline was also associated with a higher cognitive decline at
      follow-up, after adjustment for the above-cited confounding factors. This
      association was significant for word-list learning. For the changes in scores at
      word-list learning (delayed recall), regression coefficients were -0.008 +/-
      0.13, -0.09 +/- 0.13, -0.17 +/- 0.14, and -0.35 +/- 0.14 (p for trend < 0.001)
      for the second, third, fourth, and fifth quintiles of BMI at baseline when
      compared with the first quintile. No significant association was found between
      changes in BMI and cognitive function. CONCLUSIONS: Body mass index was
      independently associated both with cognitive function (word-list learning and
      Digit-Symbol Substitution Test) and changes in word-list learning in healthy,
      nondemented, middle-aged men and women.

PMID- 17030755
TI  - Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin
      labeling MRI.
AB  - OBJECTIVES: To test if arterial spin labeling (ASL) MRI could detect a pattern of
      hypoperfusion in frontotemporal dementia (FTD) vs cognitively normal (CN) control
      subjects; to determine the regional difference of perfusion between FTD and
      Alzheimer disease (AD); and to determine whether hypoperfusion in FTD correlates
      with cognitive impairment. METHODS: We included 21 patients with FTD, 24 patients
      with AD, and 25 CN subjects in this cross-sectional MRI study. All subjects had
      MRI scans including T1-weighted structural images and ASL-MR images. RESULTS: ASL
      MRI detected a pattern of hypoperfusion in right frontal regions in patients with
      FTD vs CN subjects, similar to PET and SPECT. FTD had higher perfusion than AD in
      the parietal regions and posterior cingulate. Frontal hypoperfusion in FTD
      correlated with deficits in judgment and problem solving. Adding frontal
      perfusion to gray matter (GM) atrophy significantly improved the classification
      of FTD from normal aging to 74%, and adding parietal perfusion to GM atrophy
      significantly improved the classification of FTD from AD to 75%. Combining
      frontal and parietal lobe perfusion further improved the classification of FTD
      from AD to 87%. CONCLUSION: Frontotemporal dementia and Alzheimer disease display
      different spatial distributions of hypoperfusion on arterial spin labeling MRI.
      With further development and evaluation, arterial spin labeling MRI could
      contribute to the differential diagnosis between frontotemporal dementia and
      Alzheimer disease.

PMID- 17030756
TI  - Regional brain atrophy in cognitively intact adults with a single APOE epsilon4
      allele.
AB  - OBJECTIVE: To determine whether cognitively intact adults with the APOE
      epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based
      morphometry (VBM) vs those homozygous for the epsilon3 allele. METHODS:
      Participants were healthy, cognitively intact, right-handed adults, age 19 to 80,
      who completed genotyping, neuropsychological testing, and MRI. Forty-nine
      participants had the epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4
      genotype. Gray matter data were analyzed using the general linear model as
      implemented in the Statistical Parametric Mapping package, adjusting for age and
      sex. RESULTS: The epsilon3/epsilon4 participants showed lower gray matter density
      than the epsilon3/epsilon3 participants in right medial temporal and bilateral
      frontotemporal regions as well as other areas. There were no regions in which
      epsilon3/epsilon4 participants showed higher gray matter density than
      epsilon3/epsilon3 participants. CONCLUSIONS: Regionally reduced gray matter
      density is detectable in cognitively intact adults with a single copy of the APOE
      epsilon4 allele.

PMID- 17030757
TI  - Dopamine agonists and cardiac valvulopathy in Parkinson disease: a case-control
      study.
AB  - OBJECTIVE: To determine the frequency of cardiac valvulopathy in patients with
      Parkinson disease (PD) treated with or without dopamine agonists. METHODS: We
      obtained transthoracic echocardiography and EKG in 210 consecutive patients with
      PD admitted to our hospital between September 2004 and September 2005. We
      analyzed the frequency according to the type of dopamine agonist. A case-control
      design was adopted with dopamine agonist nontreated group as the reference group,
      and multiple logistic regression analysis was conducted considering age, sex, and
      duration of illness to examine the relationships between each dopamine agonist
      and the presence of valvular abnormalities. RESULTS: The frequency of
      valvulopathy was significantly higher in the cabergoline-treated group (68.8%,
      11/16; affected patients/total) than in the dopamine agonist nontreated control
      group (17.6%, 15/85). The frequency was not different between the pergolide group
      (28.8%, 19/66) and the pramipexole group (25%, 4/16). The adjusted odds ratio was
      significantly higher in the cabergoline group (12.96, 95% CI = 3.59 to 46.85),
      compared with the pergolide group (2.18, 95% CI = 0.90 to 5.30) and pramipexole
      group (1.62, 95% CI = 0.45 to 5.87). The mean daily dose was 3.8 mg for
      cabergoline, 1.4 mg for pergolide, and 1.7 mg for pramipexole. The cumulative
      dose and treatment duration of cabergoline in the valvulopathy subgroup were
      significantly higher than in the nonvalvulopathy subgroup. CONCLUSION: The
      frequency of valvulopathy was significantly increased in the cabergoline group.
      Our results indicate that high cumulative dose and long-term treatment with
      cabergoline are risk factors for valvulopathy in patients with Parkinson disease.

PMID- 17030758
TI  - Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of
      infancy.
AB  - OBJECTIVE: To identify cryptic chromosomal deletions involving SCN1A in patients
      with severe myoclonic epilepsy of infancy (SMEI). METHODS: Thirty-nine patients
      with SMEI and without SCN1A point mutations and their parents were typed with 14
      intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and
      the extent of genomic deletions were determined by fluorescence in situ
      hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1.
      Deletion breakpoints were more finely mapped by typing single-nucleotide
      polymorphisms and microsatellite markers. RESULTS: We identified three patients
      with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size
      was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal
      chromosome in all subjects. One patient had central precocious puberty and
      palatoschisis. Genotype-phenotype correlations suggest that these clinical
      features are due to genes centromeric to SCN1A. CONCLUSIONS: Patients with severe
      myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be
      investigated for cryptic chromosomal deletions involving SCN1A. Clinical features
      other than epilepsy could be associated with SMEI as a consequence of deletions
      in contiguous genes.

PMID- 17030759
TI  - The contactin 4 gene locus at 3p26 is a candidate gene of SCA16.
AB  - OBJECTIVE: To identify of the gene responsible for the onset of spinocerebellar
      ataxia type 16 (SCA16). METHODS: We reanalyzed the linkage of the original
      Japanese pedigree using updated information, including three additional subjects.
      We then screened all exons located in the critical region. RESULTS: We reassigned
      the locus of SCA16 to 3p26.2-pter (maximum logarithm-of-odds score = 5.177) and
      identified only one point mutation (4,256C-->T) in the 3' untranslated region of
      the contactin 4 gene (CNTN4) on chromosome 3p26.2-26.3, which cosegregated with
      the disease. This mutation was not detected in 520 control subjects; moreover, we
      revised the phenotype of SCA16 from pure to complicated SCA. CONCLUSION: The
      contactin 4 gene (CNTN4) is associated with cerebellar degeneration in
      spinocerebellar ataxia type 16. Additional studies are necessary to prove 4,256C-
      >T to be a causative mutation.

PMID- 17030760
TI  - Cerebellar limb tremor and inferior olivary hypertrophy.

PMID- 17030761
TI  - Clinical features associated with impulse control disorders in Parkinson disease.
AB  - In patients with Parkinson disease (PD), impulse control disorders (ICDs) such as
      hypersexuality and pathologic gambling and shopping can be devastating
      complications of antiparkinsonian treatment. To improve their detection, we
      investigated clinical features associated with ICDs. Subjects were participants
      in a longitudinal study of PD. ICDs were associated with use of dopamine agonists
      and depressed mood, disinhibition, irritability, and appetite disturbance.

PMID- 17030762
TI  - Creatine supplementation in Parkinson disease: a placebo-controlled randomized
      pilot trial.
AB  - Mitochondrial dysfunction plays a major role in the pathogenesis of Parkinson
      disease (PD). Creatine (Cr) is an ergogenic compound that exerts neuroprotective
      effects in animal models of PD. We conducted a 2-year placebo-controlled
      randomized clinical trial on the effect of Cr in 60 patients with PD. Cr improved
      patient mood and led to a smaller dose increase of dopaminergic therapy but had
      no effect on overall Unified Parkinson's Disease Rating Scale scores or dopamine
      transporter SPECT.

PMID- 17030763
TI  - Speech and language delay are early manifestations of juvenile-onset Huntington
      disease.
AB  - The neurocognitive features of juvenile-onset Huntington disease (HD) are not
      well understood. We present three patients with onset of HD symptoms before age
      10 years in whom speech delay was the first symptom. Speech delay predated motor
      symptoms by at least 2 years, and language function was consistently impaired on
      formal testing. Screening for speech delay is particularly important in children
      with a family history of HD.

PMID- 17030764
TI  - Effect of donepezil on motor and cognitive function in Huntington disease.
AB  - Striatal cholinergic dysfunction may be important in Huntington disease (HD). We
      studied whether donepezil improves chorea, cognition, and quality of life (QoL)
      in HD. Thirty patients were randomly assigned to treatment with donepezil or
      placebo. At the doses studied, donepezil did not improve chorea, cognition, or
      QoL. Adverse events were similar between both groups. Based on this small sample
      study, donepezil was not an effective treatment for HD.

PMID- 17030765
TI  - Progression of warfarin-associated intracerebral hemorrhage after INR
      normalization with FFP.
AB  - To identify hematoma progression in patients with warfarin-associated
      intracerebral hemorrhage (ICH) despite international normalized ratio (INR)
      normalization with fresh-frozen plasma (FFP), we reviewed 45 patients with
      warfarin-associated ICH given FFP. The median time for door to INR normalization
      was 30 hours (14 to 49.5), with 4 patients' hematomas enlarging after INR
      normalization. FFP is associated with substantial time delay to actual
      administration and pulmonary edema and may not prevent progression of ICH despite
      INR normalization.

PMID- 17030766
TI  - Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from
      WASID.
AB  - The WASID trial showed no advantage of warfarin over aspirin for preventing the
      primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In
      analyses of selected subgroups, there was no definite benefit from warfarin.
      Warfarin reduced the risk of the primary endpoint among patients with basilar
      artery stenosis, but there was no reduction in stroke in the basilar artery
      territory or benefit for vertebral artery stenosis or posterior circulation
      disease in general.

PMID- 17030767
TI  - Predictors of hospital length of stay and cost in patients with intracerebral
      hemorrhage.
AB  - We used the 2002 Healthcare Cost and Utilization Project Nationwide Inpatient
      Sample to assess hospital length of stay (LOS) and cost among adults with a
      principal diagnosis of intracerebral hemorrhage (n = 13,239). Sixty-nine percent
      of patients were aged > or =65 years, and 31% died during hospitalization. Mean
      LOS (cost) was 7.7 days (15,256 dollars) (survivors: 9.6 days, 17,442 dollars).
      Patient, hospital, and payer characteristics accounted for 69.1% of variation in
      cost per discharge.

PMID- 17030768
TI  - Gender differences in self-report of recovery after stroke: the Northern
      Manhattan Study.
AB  - We compared subjective responses to simple questions after stroke with
      interviewer-assessed stroke outcome measures. Among those in the highest
      functional category, women were more likely to report incomplete recovery and
      greater need for help than men. Among these women, depressed mood was associated
      with a response of a need for help despite a good functional recovery. Self
      reported responses in stroke outcome assessments require further validation by
      gender and may need to consider the confounding effects of depression.

PMID- 17030769
TI  - What's inside the art? The influence of frontotemporal dementia in art
      production.
AB  - We evaluated the productions of an artist with frontotemporal lobar degeneration
      from before dementia onset until she was fully symptomatic. We noted an
      improvement of technique that might be related to sparing and disinhibition of
      the right posterior neocortex. There was a reduction of closure (completeness of
      the painting), possibly induced by impersistence and a decrease in evocative
      impact that might be explained by frontal and anterotemporal-limbic dysfunction.

PMID- 17030770
TI  - Elevated CSF free kappa light chains correlate with disability prognosis in
      multiple sclerosis.
AB  - Elevated CSF free kappa light chains (FKLCs) may predict disability in multiple
      sclerosis (MS). We reviewed records of 57 patients with MS with 15-year median
      follow-up for correlations of disability and CSF FKLCs. Levels > or = 1.53
      microg/mL predicted progression to need for ambulatory assistance during follow
      up (specificity 87.5%, positive predictive value 88.9%) or within 10 years
      (specificity 78.6%, positive predictive value 66.7%).

PMID- 17030771
TI  - Liver test abnormalities in multiple sclerosis: findings from placebo-treated
      patients.
AB  - The risk of an abnormal liver test in 813 patients with multiple sclerosis or
      clinically isolated syndrome enrolled in placebo arms of clinical trials was
      greater than expected for alanine aminotransferase (ALT) (relative risk [RR] 3.7;
      95% CI: 2.3 to 6.0) and aspartate aminotransferase (AST) (RR 2.2; 95% CI: 1.3 to
      3.6), although not alkaline phosphatase (AP) or total bilirubin, at first
      presentation. Abnormal test results were associated with higher body mass index
      (ALT only), male gender (ALT only), and a relapsing-remitting (vs secondary
      progressive) course (ALT and AST only).

PMID- 17030772
TI  - Development and evaluation of a self-administered version of the ALSFRS-R.
AB  - We evaluated the reliability and sensitivity to change over time of a newly
      developed self-administered version of the ALS functional rating scale-revised
      (ALSFRS-R) in 60 consecutive patients from an ALS clinic. The self-administered
      ALSFRS-R showed excellent reliability (intraclass correlation = 0.93, 95% CI: 088
      to 0.96) and similar sensitivity to change over time vs the standard evaluator
      administered ALSFRS-R.

PMID- 17030773
TI  - Valproate effects on kinetics of lamotrigine in pregnancy and treatment with oral
      contraceptives.
AB  - In eight women treated with lamotrigine monotherapy, the lamotrigine dose/plasma
      concentration (D/C) ratio increased by 295% from baseline outside pregnancy to
      midgestation, whereas in six women treated with lamotrigine in combination with
      valproate, the increase was only 60%. No difference in lamotrigine D/C ratio was
      found between users and nonusers of oral contraceptives comedicated with
      valproate. Valproate seems to reduce the induction of lamotrigine metabolism
      associated with pregnancy or use of contraceptives.

PMID- 17030774
TI  - Clinical features of chromosome 16q22.1 linked autosomal dominant cerebellar
      ataxia in Japanese.
AB  - Chromosome 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA) is
      strongly associated with a substitution in the puratrophin-1 gene. This locus
      overlaps with spinocerebellar ataxia type 4 (SCA4) which shows ataxia with
      prominent sensory axonal neuropathy. We found that 16q-ADCA is a common ADCA
      subtype in the Tohoku District of Japan. The clinical feature of Japanese 16q
      ADCA is characterized as late-onset pure cerebellar ataxia.

PMID- 17030775
TI  - Metastases to the pineal gland.
AB  - We identified 10 patients with symptomatic metastases to the pineal gland. We
      present the clinical and radiographic findings in this syndrome. Leptomeningeal
      metastases occur frequently and are a poor prognostic factor. In all cases, the
      primary cancer was clinically silent, either in remission (six cases) or
      previously undiagnosed (four cases). Hence, metastatic disease, albeit uncommon,
      should be considered in the differential diagnosis of pineal tumors.

PMID- 17030776
TI  - Homonymous hemianopsia complicating treatment of postoperative epistaxis.

PMID- 17030777
TI  - Crossed aphasia elicited by direct cortical stimulation.

PMID- 17030778
TI  - Effect of topiramate on cognition in obese children.

PMID- 17030779
TI  - Improvement with corticosteroids and azathioprine in GAD65-associated cerebellar
      ataxia.

PMID- 17030780
TI  - ACE activity in CSF of patients with mild cognitive impairment and Alzheimer
      disease.

PMID- 17030781
TI  - Action myoclonus-renal failure syndrome: a cause for worsening tremor in young
      adults.

PMID- 17030783
TI  - A randomized study of two interferon-beta treatments in relapsing-remitting
      multiple sclerosis.

PMID- 17030784
TI  - Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled
      clinical trial.

PMID- 17030785
TI  - Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS.

PMID- 17030786
TI  - DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient
      cells to bulky rhodium(III) intercalators.
AB  - Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and
      deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium
      intercalators target DNA base mismatches with high specificity. Here we describe
      the application of bulky rhodium intercalators to inhibit cellular proliferation
      differentially in MMR-deficient cells compared with cells that are MMR
      proficient. Preferential inhibition by the rhodium complexes associated with MMR
      deficiency is seen both in a human colon cancer cell line and in normal mouse
      fibroblast cells; the inhibition of cellular proliferation depends strictly on
      the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation
      is found to correlate with DNA mismatch targeting by the bulky
      metallointercalators. It is the Delta-isomer that is active both in targeting
      base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium
      intercalators promote strand cleavage at the mismatch site with photoactivation,
      and we observe that the cellular response is enhanced with photoactivation.
      Targeting DNA mismatches may therefore provide a cell-selective strategy for
      chemotherapeutic design.

PMID- 17030787
TI  - Programming social, cognitive, and neuroendocrine development by early exposure
      to novelty.
AB  - Mildly stressful early life experiences can potentially impact a broad range of
      social, cognitive, and physiological functions in humans, nonhuman primates, and
      rodents. Recent rodent studies favor a maternal-mediation hypothesis that
      considers maternal-care differences induced by neonatal stimulation as the cause
      of individual differences in offspring development. Using neonatal novelty
      exposure, a neonatal stimulation paradigm that dissociates maternal individual
      differences from a direct stimulation effect on the offspring, we investigated
      the effect of early exposures to novelty on a diverse range of psychological
      functions using several assessment paradigms. Pups that received brief neonatal
      novelty exposures away from the home environment showed enhancement in spatial
      working memory, social competition, and corticosterone response to surprise
      during adulthood compared with their home-staying siblings. These functional
      enhancements in novelty-exposed rats occurred despite evidence that maternal care
      was directed preferentially toward home-staying instead of novelty-exposed pups,
      indicating that greater maternal care is neither necessary nor sufficient for
      these early stimulation-induced functional enhancements. We suggest a unifying
      maternal-modulation hypothesis, which distinguishes itself from the maternal
      mediation hypothesis in that (i) neonatal stimulation can have direct effects on
      pups, cumulatively leading to long-term improvement in adult offspring; and (ii)
      maternal behavior can attenuate or potentiate these effects, thereby decreasing
      or increasing this long-term functional improvement.

PMID- 17030788
TI  - Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene
      expression in skeletal muscle: Role of PGC-1alpha.
AB  - Previous investigations show that intracerebroventricular administration of a
      potent inhibitor of fatty acid synthase, C75, increases the level of its
      substrate, malonyl-CoA, in the hypothalamus. The "malonyl-CoA signal" is rapidly
      transmitted to skeletal muscle by the sympathetic nervous system, increasing
      fatty acid oxidation, uncoupling protein-3 (UCP3) expression, and thus, energy
      expenditure. Here, we show that intracerebroventricular or intraperitoneal
      administration of C75 increases the number of mitochondria in white and red
      (soleus) skeletal muscle. Consistent with signal transmission from the
      hypothalamus by the sympathetic nervous system, centrally administered C75
      rapidly (< or =2 h) up-regulated the expression (in skeletal muscle) of the beta
      adrenergic signaling molecules, i.e., norepinephrine, beta3-adrenergic receptor,
      and cAMP; the transcriptional regulators peroxisomal proliferator activator
      regulator gamma coactivator 1alpha (PGC-1alpha) and estrogen receptor-related
      receptor alpha (ERRalpha); and the expression of key oxidative mitochondrial
      enzymes, including pyruvate dehydrogenase kinase, medium-chain length fatty acyl
      CoA dehydrogenase, ubiquinone-cytochrome c reductase, cytochrome oxidase, as well
      as ATP synthase and UCP3. The role of PGC-1alpha in mediating these responses in
      muscle was assessed with C2C12 myocytes in cell culture. Consistent with the in
      vivo response, adenovirus-directed expression of PGC-1alpha in C2C12 muscle cells
      provoked the phosphorylation/inactivation and reduced expression of acetyl-CoA
      carboxylase 2, causing a reduction of the malonyl-CoA concentration. These
      effects, coupled with an increased carnitine palmitoyltransferase 1b, led to
      increased fatty acid oxidation. PGC-1alpha also increased the expression of
      ERRalpha, PPARalpha, and enzymes that support mitochondrial fatty acid oxidation,
      ATP synthesis, and thermogenesis, apparently mediated by an increased expression
      of UCP3.

PMID- 17030790
TI  - Mathematical analysis of locomotor behavior by mice in a radial maze.
AB  - We investigated the effects of beta-estradiol on the locomotor behavior of female
      mice in a radial maze. Data comprising the total distance traveled during each
      arm entry were obtained from video records of six consecutive daily recording
      sessions. Distributions of these data were bimodal for both ovariectomized
      control and beta-estradiol-treated ovariectomized subjects. Data were fit with
      the sum of two gamma probability distributions. Three parameters of the analytic
      fits were useful for quantifying the effect of beta-estradiol on locomotor
      behavior: (i) the sampling distance (median of the total distance traveled during
      each arm entry in the short-distance peak of a bimodal distribution), (ii) the
      committed distance (median of the total per-arm-entry distance traveled in the
      long-distance peak), and (iii) the partition distance (distance represented by
      the minimum between the two peaks). Analysis showed that for sampling-distance
      arm entries beta-estradiol typically had little if any significant effect on
      female locomotor behavior, whereas it significantly increased the total distance
      traveled during committed-distance arm entries on the first 2 days of exposure to
      the empty maze. beta-Estradiol also increased the ability of females to
      discriminate between empty maze arms and arms that contained intact or castrated
      male mice and partially prevented loss of this capacity after removal of the
      males.

PMID- 17030789
TI  - Increased susceptibility to bacterial superinfection as a consequence of innate
      antiviral responses.
AB  - The reason why severe localized or systemic virus infections enhance and
      aggravate bacterial superinfection is poorly understood. Here we show that virus
      induced IFN type I caused apoptosis in bone marrow granulocytes, drastically
      reduced granulocyte infiltrates at the site of bacterial superinfection, caused
      up to 1,000-fold higher bacterial titers in solid organs, and increased disease
      susceptibility. The finding that the innate antiviral immune response reduces the
      antibacterial granulocyte defense offers an explanation for enhanced
      susceptibility to bacterial superinfection during viral disease.

PMID- 17030791
TI  - G protein-coupled receptors sense fluid shear stress in endothelial cells.
AB  - Hemodynamic shear stress stimulates a number of intracellular events that both
      regulate vessel structure and influence development of vascular pathologies. The
      precise molecular mechanisms by which endothelial cells transduce this mechanical
      stimulus into intracellular biochemical response have not been established. Here,
      we show that mechanical perturbation of the plasma membrane leads to ligand
      independent conformational transitions in a G protein-coupled receptor (GPCR). By
      using time-resolved fluorescence microscopy and GPCR conformation-sensitive FRET
      we found that stimulation of endothelial cells with fluid shear stress, hypotonic
      stress, or membrane fluidizing agent leads to a significant increase in activity
      of bradykinin B2 GPCR in endothelial cells. The GPCR conformational dynamics was
      detected by monitoring redistribution of GPCRs between inactive and active
      conformations in a single endothelial cell under fluid shear stress in real time.
      We show that this response can be blocked by a B(2)-selective antagonist. Our
      data demonstrate that changes in cell membrane tension and membrane fluidity
      affect conformational dynamics of GPCRs. Therefore, we suggest that GPCRs are
      involved in mediating primary mechanochemical signal transduction in endothelial
      cells. We anticipate our experiments to be a starting point for more
      sophisticated studies of the effects of changes in lipid bilayer environment on
      GPCR conformational dynamics. Furthermore, because GPCRs are a major target of
      drug development, a detailed characterization of mechanochemical signaling via
      the GPCR pathway will be relevant for the development of new antiatherosclerosis
      drugs.

PMID- 17030792
TI  - Protein folding is slaved to solvent motions.
AB  - Proteins, the workhorses of living systems, are constructed from chains of amino
      acids, which are synthesized in the cell based on the instructions of the genetic
      code and then folded into working proteins. The time for folding varies from
      microseconds to hours. What controls the folding rate is hotly debated. We
      postulate here that folding has the same temperature dependence as the alpha
      fluctuations in the bulk solvent but is much slower. We call this behavior
      slaving. Slaving has been observed in folded proteins: Large-scale protein
      motions follow the solvent fluctuations with rate coefficient k(alpha) but can be
      slower by a large factor. Slowing occurs because large-scale motions proceed in
      many small steps, each determined by k(alpha). If conformational motions of
      folded proteins are slaved, so a fortiori must be the motions during folding. The
      unfolded protein makes a Brownian walk in the conformational space to the folded
      structure, with each step controlled by k(alpha). Because the number of
      conformational substates in the unfolded protein is extremely large, the folding
      rate coefficient, k(f), is much smaller than k(alpha). The slaving model implies
      that the activation enthalpy of folding is dominated by the solvent, whereas the
      number of steps n(f) = k(alpha)/k(f) is controlled by the number of accessible
      substates in the unfolded protein and the solvent. Proteins, however, undergo not
      only alpha- but also beta-fluctuations. These additional fluctuations are local
      protein motions that are essentially independent of the bulk solvent fluctuations
      and may be relevant at late stages of folding.

PMID- 17030793
TI  - Comparative genomics of the lactic acid bacteria.
AB  - Lactic acid-producing bacteria are associated with various plant and animal
      niches and play a key role in the production of fermented foods and beverages. We
      report nine genome sequences representing the phylogenetic and functional
      diversity of these bacteria. The small genomes of lactic acid bacteria encode a
      broad repertoire of transporters for efficient carbon and nitrogen acquisition
      from the nutritionally rich environments they inhabit and reflect a limited range
      of biosynthetic capabilities that indicate both prototrophic and auxotrophic
      strains. Phylogenetic analyses, comparison of gene content across the group, and
      reconstruction of ancestral gene sets indicate a combination of extensive gene
      loss and key gene acquisitions via horizontal gene transfer during the
      coevolution of lactic acid bacteria with their habitats.

PMID- 17030794
TI  - The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic
      powerhouse.
AB  - Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil
      actinomycete that catabolizes a wide range of compounds and represents a genus of
      considerable industrial interest. RHA1 has one of the largest bacterial genomes
      sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear
      chromosome and three linear plasmids. A targeted insertion methodology was
      developed to determine the telomeric sequences. RHA1's 9,145 predicted protein
      encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many
      of the oxygenases occur in the numerous pathways predicted to degrade aromatic
      compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide
      synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes,
      providing evidence that rhodococci harbor an extensive secondary metabolism.
      Among sequenced genomes, RHA1 is most similar to those of nocardial and
      mycobacterial strains. The genome contains few recent gene duplications.
      Moreover, three different analyses indicate that RHA1 has acquired fewer genes by
      recent horizontal transfer than most bacteria characterized to date and far fewer
      than Burkholderia xenovorans LB400, whose genome size and catabolic versatility
      rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically
      similar bacteria can evolve large genomes by different means. Overall, RHA1
      appears to have evolved to simultaneously catabolize a diverse range of plant
      derived compounds in an O(2)-rich environment. In addition to establishing RHA1
      as an important model for studying actinomycete physiology, this study provides
      critical insights that facilitate the exploitation of these industrially
      important microorganisms.

PMID- 17030795
TI  - Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate
      controls endosome morphology and selective cargo sorting.
AB  - It is increasingly recognized that the compartmental organization of signaling
      processes has a profound influence on cellular behavior. However, our inability
      to influence these compartmental events in a spatially restricted and acute
      manner limits our understanding of causation. To determine whether local
      compartmental loss of a phosphoinositide disrupts the normal traffic of specific
      cargoes through endosomes, we developed the use of a regulated dimerization
      device, here designed to compartmentally modify the phosphoinositide content of
      Rab5-positive endosomes. This modification is effected through the specific
      regulated recruitment of the 3-phosphatase myotubularin to endosomal membranes in
      intact cells. The selective manipulation of endosomal phosphatidylinositols (PIs)
      demonstrates that it is the phosphatidylinositol 3-phosphate (PtdIns3P) or its
      metabolite PtdIns(3,5)P2 within this compartment that determines the normal
      maturation of the endosomal compartment and the flux of receptors through it. On
      local loss of PtdIns3P/PtdIns(3,5)P2, the endosomal compartment itself fails to
      continue its normal maturation process, leading to the microtubule-dependent
      tubularization of the endosomal network. Furthermore, it is shown that endosomal
      PtdIns3P/PtdIns(3,5)P2 is necessary for transferrin receptor traffic through this
      compartment while having an effect on EGF receptor (EGFR) entry into and sorting
      from this endosome compartment. The ability to acutely and selectively influence
      compartmental behavior as exemplified here for endomsomes clearly illustrates the
      power of the approach used to dissect the role of localized signals and events.

PMID- 17030796
TI  - Acrolein is a major cigarette-related lung cancer agent: Preferential binding at
      p53 mutational hotspots and inhibition of DNA repair.
AB  - The tumor suppressor gene p53 is frequently mutated in cigarette smoke (CS)
      related lung cancer. The p53 binding pattern of carcinogenic polycyclic aromatic
      hydrocarbons (PAHs) found in CS coincides with the p53 mutational pattern found
      in lung cancer, and PAHs have thus been considered to be major culprits for lung
      cancer. However, compared with other carcinogenic compounds, such as aldehydes,
      the amount of PAHs in CS is minute. Acrolein (Acr) is abundant in CS, and it can
      directly adduct DNA. Acr-DNA adducts, similar to PAH-DNA adducts, induce
      predominantly G-to-T transversions in human cells. These findings raise the
      question of whether Acr-DNA adducts are responsible for p53 mutations in CS
      related lung cancer. To determine the role of Acr-DNA adducts in p53 mutagenesis
      in CS-related lung cancer we mapped the distribution of Acr-DNA adducts at the
      sequence level in the p53 gene of lung cells using the UvrABC incision method in
      combination with ligation-mediated PCR. We found that the Acr-DNA binding pattern
      is similar to the p53 mutational pattern in human lung cancer. Acr preferentially
      binds at CpG sites, and this enhancement of binding is due to cytosine
      methylation at these sequences. Furthermore, we found that Acr can greatly reduce
      the DNA repair capacity for damage induced by benzo[a]pyrene diol epoxide.
      Together these results suggest that Acr is a major etiological agent for CS
      related lung cancer and that it contributes to lung carcinogenesis through two
      detrimental effects: DNA damage and inhibition of DNA repair.

PMID- 17030797
TI  - Burkholderia xenovorans LB400 harbors a multi-replicon, 9.73-Mbp genome shaped
      for versatility.
AB  - Burkholderia xenovorans LB400 (LB400), a well studied, effective polychlorinated
      biphenyl-degrader, has one of the two largest known bacterial genomes and is the
      first nonpathogenic Burkholderia isolate sequenced. From an evolutionary
      perspective, we find significant differences in functional specialization between
      the three replicons of LB400, as well as a more relaxed selective pressure for
      genes located on the two smaller vs. the largest replicon. High genomic
      plasticity, diversity, and specialization within the Burkholderia genus are
      exemplified by the conservation of only 44% of the genes between LB400 and
      Burkholderia cepacia complex strain 383. Even among four B. xenovorans strains,
      genome size varies from 7.4 to 9.73 Mbp. The latter is largely explained by our
      findings that >20% of the LB400 sequence was recently acquired by means of
      lateral gene transfer. Although a range of genetic factors associated with in
      vivo survival and intercellular interactions are present, these genetic factors
      are likely related to niche breadth rather than determinants of pathogenicity.
      The presence of at least eleven "central aromatic" and twenty "peripheral
      aromatic" pathways in LB400, among the highest in any sequenced bacterial genome,
      supports this hypothesis. Finally, in addition to the experimentally observed
      redundancy in benzoate degradation and formaldehyde oxidation pathways, the fact
      that 17.6% of proteins have a better LB400 paralog than an ortholog in a
      different genome highlights the importance of gene duplication and repeated
      acquirement, which, coupled with their divergence, raises questions regarding the
      role of paralogs and potential functional redundancies in large-genome microbes.

PMID- 17030798
TI  - Methionine catabolism in Arabidopsis cells is initiated by a gamma-cleavage
      process and leads to S-methylcysteine and isoleucine syntheses.
AB  - Despite recent progress in elucidating the regulation of methionine (Met)
      synthesis, little is known about the catabolism of this amino acid in plants. In
      this article, we present several lines of evidence indicating that the cleavage
      of Met catalyzed by Met gamma-lyase is the first step in this process. First, we
      cloned an Arabidopsis cDNA coding a functional Met gamma-lyase (AtMGL), a
      cytosolic enzyme catalyzing the conversion of Met into methanethiol, alpha
      ketobutyrate, and ammonia. AtMGL is present in all of the Arabidopsis organs and
      tissues analyzed, except in quiescent dry mature seeds, thus suggesting that
      AtMGL is involved in the regulation of Met homeostasis in various situations.
      Also, we demonstrated that the expression of AtMGL was induced in Arabidopsis
      cells in response to high Met levels, probably to bypass the elevated Km of the
      enzyme for Met. Second, [13C]-NMR profiling of Arabidopsis cells fed with
      [13C]Met allowed us to identify labeled S-adenosylmethionine, S-methylmethionine,
      S-methylcysteine (SMC), and isoleucine (Ile). The unexpected production of SMC
      and Ile was directly associated to the function of Met gamma-lyase. Indeed, we
      showed that part of the methanethiol produced during Met cleavage could react
      with an activated form of serine to produce SMC. The second product of Met
      cleavage, alpha-ketobutyrate, entered the pathway of Ile synthesis in plastids.
      Together, these data indicate that Met catabolism in Arabidopsis cells is
      initiated by a gamma-cleavage process and can result in the formation of the
      essential amino acid Ile and a potential storage form for sulfide or methyl
      groups, SMC.

PMID- 17030799
TI  - Cell-surface heparan sulfate proteoglycans are essential components of the
      unconventional export machinery of FGF-2.
AB  - FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals
      through a ternary complex with high-affinity FGF receptors and heparan sulfate
      proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great
      detail, its mechanism of release from cells, which is independent of the
      classical secretory pathway, remains elusive. To test the hypothesis that FGF-2
      secretion is linked to its cell-surface ligands, we studied FGF-2 release using
      mutants defective for HSPG binding and cells with impaired HSPG biosynthesis.
      Here, we report that a functional interaction between FGF-2 and HSPGs is required
      for net export of FGF-2 from mammalian cells. FGF-2 release requires
      extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form
      a molecular trap that drives FGF-2 translocation across the plasma membrane.

PMID- 17030800
TI  - Pseudomonas aeruginosa type III-secreted toxin ExoT inhibits host-cell division
      by targeting cytokinesis at multiple steps.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that requires preexisiting
      epithelial injury to cause acute infections. We report that P. aeruginosa
      inhibits mammalian cytokinesis in a type III secretion system and exotoxin T
      (ExoT)-dependent manner. ExoT is a bifunctional type III secretion system
      effector protein that contains an N-terminal GTPase-activating protein domain and
      a C-terminal ADP-ribosyl transferase domain. Each of its domains inhibits
      cytokinesis in a kinetically, morphologically, and mechanistically distinct
      manner. The GTPase-activating protein-mediated inhibition of cytokinesis occurs
      early, likely as a consequence of its inhibitory effect on RhoA. The ADP-ribosyl
      transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2
      localization to the midbody, an event essential for completion of cytokinesis.
      These findings provide an example of a bacterial pathogen targeting cytokinesis.

PMID- 17030801
TI  - Dual function of an Arabidopsis transcription factor DREB2A in water-stress
      responsive and heat-stress-responsive gene expression.
AB  - Transcription factor DREB2A interacts with a cis-acting dehydration-responsive
      element (DRE) sequence and activates expression of downstream genes involved in
      drought- and salt-stress response in Arabidopsis thaliana. Intact DREB2A
      expression does not activate downstream genes under normal growth conditions. A
      negative regulatory domain exists in the central region of DREB2A, and deletion
      of this region transforms DREB2A to a constitutive active form (DREB2A CA). We
      carried out microarray analysis of transgenic Arabidopsis-overexpressing DREB2A
      CA and found that the overexpression of DREB2A CA induces not only drought- and
      salt-responsive genes but also heat-shock (HS)-related genes. Moreover, we found
      that transient induction of the DREB2A occurs rapidly by HS stress, and that the
      sGFP-DREB2A protein accumulates in nuclei of HS-stressed cells. DREB2A up
      regulated genes were classified into three groups based on their expression
      patterns: genes induced by HS, genes induced by drought stress, and genes induced
      by both HS and drought stress. DREB2A up-regulated genes were down-regulated in
      DREB2A knockout mutants under stress conditions. Thermotolerance was
      significantly increased in plants overexpressing DREB2A CA and decreased in
      DREB2A knockout plants. Collectively, these results indicate that DREB2A
      functions in both water and HS-stress responses.

PMID- 17030802
TI  - Cell-free formation of misfolded prion protein with authentic prion infectivity.
AB  - Prion propagation has been modeled in vitro; however, the low infectious titer of
      PrP(Sc) thus generated has cast doubt on the "protein-only" hypothesis. Here we
      show that prion delivery on suitable nitrocellulose carrier particles abrogates
      the apparent dissociation of PrP(Sc) and infectivity. Misfolded prion protein
      generated by protein misfolding cyclic amplification is as infectious as
      authentic brain-derived PrP(Sc) provided that confounding effects related to
      differences in the size distribution of prion protein aggregates generated in
      vitro and consecutive differences in regard to biological clearance are
      abolished.

PMID- 17030803
TI  - Combinatorially selected defense peptides protect plant roots from pathogen
      infection.
AB  - Agricultural productivity and sustainability are continually challenged by
      emerging and indigenous pathogens. Currently, many pathogens can be combatted
      only with biocides or environmentally dangerous fumigants. Here, we report a
      rapid and pathogen-specific strategy to reduce infection by organisms that target
      plant roots. Combinatorially selected defense peptides, previously shown to
      effect premature encystment of Phytophthora capsici zoospores, were fused to
      maize cytokinin oxidase/dehydrogenase as a display scaffold. When expressed in
      tomato roots, the peptide-scaffold constructs were secreted and accumulated to
      sufficient concentrations in the rhizosphere to induce zoospore encystment and
      thereby deter taxis to the root surface. Pathogen infection was significantly
      inhibited in roots expressing bioactive peptides fused to the maize cytokinin
      oxidase/dehydrogenase scaffold. This peptide-delivery technology is broadly
      applicable for rapid development of plant defense attributes against plant
      pathogens.

PMID- 17030804
TI  - Structural basis for Rab11-dependent membrane recruitment of a family of Rab11
      interacting protein 3 (FIP3)/Arfophilin-1.
AB  - Family of Rab11-interacting protein (FIP)3/Arfophlin-1 and FIP4/Arfophilin-2 are
      dual effectors for Rab11 and ADP ribosylation factor (ARF)5/ARF6, which are
      involved in membrane delivery from recycling endosomes to the plasma membrane
      during cytokinesis. Here, we define the distinct C-terminal binding regions of
      FIP3 and FIP4 for Rab11 and ARF5/ARF6. Furthermore, we determined the crystal
      structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. The
      long amphiphilic alpha-helix of FIP3-RBD forms a parallel coiled-coil homodimer,
      with two symmetric interfaces with two Rab11 molecules. The hydrophobic side of
      the RBD helix is involved in homodimerization and mediates the interaction with
      the Rab11 switch 1 region, whereas the opposite hydrophilic side interacts with
      the Rab11 switch 2 and is the major factor contributing to the binding
      specificity. The bivalent interaction of FIP3 with Rab11 at the C terminus allows
      FIP3 to coordinately function with other binding partners, including ARFs.

PMID- 17030805
TI  - A seven-helix coiled coil.
AB  - Coiled-coil proteins contain a characteristic seven-residue sequence repeat whose
      positions are designated a to g. The interacting surface between alpha-helices in
      a classical coiled coil is formed by interspersing nonpolar side chains at the a
      and d positions with hydrophilic residues at the flanking e and g positions. To
      explore how the chemical nature of these core amino acids dictates the overall
      coiled-coil architecture, we replaced all eight e and g residues in the GCN4
      leucine zipper with nonpolar alanine side chains. Surprisingly, the alanine
      containing mutant forms a stable alpha-helical heptamer in aqueous solution. The
      1.25-A resolution crystal structure of the heptamer reveals a parallel seven
      stranded coiled coil enclosing a large tubular channel with an unusual heptad
      register shift between adjacent staggered helices. The overall geometry comprises
      two interleaved hydrophobic helical screws of interacting cross-sectional a and d
      layers that have not been seen before. Moreover, asparagines at the a positions
      play an essential role in heptamer formation by participating in a set of buried
      interhelix hydrogen bonds. These results demonstrate that heptad repeats
      containing four hydrophobic positions can direct assembly of complex, higher
      order coiled-coil structures with rich diversity for close packing of alpha
      helices.

PMID- 17030806
TI  - An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1
      replication in CD4+ Jurkat T cells.
AB  - GB virus type C (GBV-C) is an apparently nonpathogenic virus that replicates in T
      and B lymphocytes and is a common cause of persistent human infection. Among HIV
      1-infected individuals, persistent coinfection with GBV-C is associated with
      prolonged survival, and infection of blood mononuclear cells or CD4+ T cells with
      GBV-C and HIV in vitro results in significantly reduced HIV-1 replication. To
      date, the viral protein(s) that lead to HIV inhibition have not been identified.
      The GBV-C nonstructural phosphoprotein (NS5A) is predicted to have pleotropic
      effects on cells, including interactions with the IFN-induced dsRNA-activated
      protein kinase (PKR). We studied GBV-C NS5A to determine whether it is involved
      in inhibition of HIV replication. GBV-C NS5A protein from an isolate that was
      cleared by IFN therapy did not inhibit PKR, whereas NS5A from an isolate that was
      not cleared by IFN-inhibited PKR function in a yeast genetic system. Both of
      these GBV-C NS5A proteins were expressed in a CD4+ T cell line (Jurkat), and both
      induced a potent, dose-dependent inhibition of HIV-1 replication, thus the effect
      was independent of PKR inhibition. NS5A induced the release of the chemokine SDF
      1 and decreased surface expression of the HIV coreceptor CXCR4, potentially
      explaining the HIV inhibition. Deletion mapping of the NS5A protein found that an
      85-aa region between amino acids 152 and 237 inhibits HIV-1 replication. Thus,
      GBV-C NS5A protein alters the cellular milieu necessary for HIV-1 replication and
      may provide a previously undescribed therapeutic approach for anti-HIV therapy.

PMID- 17030807
TI  - High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition.
AB  - APOBEC3G (A3G) and related deoxycytidine deaminases are potent intrinsic
      antiretroviral factors. A3G is expressed either as an enzymatically active low
      molecular-mass (LMM) form or as an enzymatically inactive high-molecular-mass
      (HMM) ribonucleoprotein complex. Resting CD4 T cells exclusively express LMM A3G,
      where it functions as a powerful postentry restriction factor for HIV-1.
      Activation of CD4 T cells promotes the recruitment of LMM A3G into 5- to 15-MDa
      HMM complexes whose function is unknown. Using tandem affinity purification
      techniques coupled with MS, we identified Staufen-containing RNA-transporting
      granules and Ro ribonucleoprotein complexes as specific components of HMM A3G
      complexes. Analysis of RNAs in these complexes revealed Alu and small Y RNAs, two
      of the most prominent nonautonomous mobile genetic elements in human cells. These
      retroelement RNAs are recruited into Staufen-containing RNA-transporting granules
      in the presence of A3G. Retrotransposition of Alu and hY RNAs depends on the
      reverse transcriptase machinery provided by long interspersed nucleotide elements
      1 (L1). We now show that A3G greatly inhibits L1-dependent retrotransposition of
      marked Alu retroelements not by inhibiting L1 function but by sequestering Alu
      RNAs in cytoplasmic HMM A3G complexes away from the nuclear L1 enzymatic
      machinery. These findings identify nonautonomous Alu and hY retroelements as
      natural cellular targets of A3G and highlight how different forms of A3G uniquely
      protect cells from the threats posed by exogenous retroviruses (LMM A3G) and
      endogenous retroelements (HMM A3G).

PMID- 17030808
TI  - Human fronto-mesolimbic networks guide decisions about charitable donation.
AB  - Humans often sacrifice material benefits to endorse or to oppose societal causes
      based on moral beliefs. Charitable donation behavior, which has been the target
      of recent experimental economics studies, is an outstanding contemporary
      manifestation of this ability. Yet the neural bases of this unique aspect of
      human altruism, which extends beyond interpersonal interactions, remain obscure.
      In this article, we use functional magnetic resonance imaging while participants
      anonymously donated to or opposed real charitable organizations related to major
      societal causes. We show that the mesolimbic reward system is engaged by
      donations in the same way as when monetary rewards are obtained. Furthermore,
      medial orbitofrontal-subgenual and lateral orbitofrontal areas, which also play
      key roles in more primitive mechanisms of social attachment and aversion,
      specifically mediate decisions to donate or to oppose societal causes.
      Remarkably, more anterior sectors of the prefrontal cortex are distinctively
      recruited when altruistic choices prevail over selfish material interests.

PMID- 17030809
TI  - Visual saliency and texture segregation without feature gradient.
AB  - A central notion in the study of texture segregation is that of feature gradient
      (or feature contrast). In orientation-based texture segregation, orientation
      gradients have indeed played a fundamental role in explaining behavioral results.
      Here, however, we show that general, smoothly varying, orientation-defined
      textures (ODTs) exhibit striking perceptual singularities that are completely
      unpredictable from orientation gradients. These singularities defy not only
      popular texture segregation theories but also virtually all computational
      segmentation methods, and they confound previous behavioral studies with smoothly
      varying ODTs. We provide psychophysical evidence that perceptual singularities in
      smooth ODTs are salient visual features consistent across observers and with
      significant effect on the perception and segregation of oriented textures. We
      further show that, although orientation gradients cannot predict them, perceptual
      singularities in smooth ODTs emerge directly from, and can be spatially localized
      by, two ODT curvatures. Given the traditional role of feature gradients in early
      vision, the significance of these findings extends well beyond orientation-based
      texture segregation to issues ranging from curve integration and fragment
      grouping, through the perception of 3D shape, to the functional organization of
      the primary visual cortex.

PMID- 17030810
TI  - L-Kynurenine, an amino acid identified as a sex pheromone in the urine of
      ovulated female masu salmon.
AB  - Many animals employ sex pheromones to find mating partners during their
      reproductive seasons. However, most sex pheromones of vertebrates remain to be
      identified. Over the past 20 years, steroids and prostaglandins have been
      identified as sex pheromones in several fishes. These pheromones are broadly
      termed "hormonal pheromones" because they or their precursors act as hormones in
      these fishes. Hitherto, no other type of sex pheromone has been unambiguously
      identified in teleost fish. Here we report the identification of a "nonhormonal
      pheromone" in teleost fish. The urine of the reproductively mature female masu
      salmon (Oncorhynchus masou) contains a male-attracting pheromone. Bioassay-guided
      fractionation yielded an active compound that was identical to L-kynurenine in
      spectral and chromatographic properties. L-Kynurenine is a major metabolite of L
      tryptophan in vertebrates. This pheromone elicits a male-specific behavior at
      even picomolar concentrations; its electrophysiological threshold is 10(-14) M. L
      Kynurenine is a reasonable substance for female masu salmon to advertise their
      readiness for mating.

PMID- 17030811
TI  - Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in
      rats and humans.
AB  - MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The
      tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN)
      types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4,
      excluding the homologs of the genes responsible for the MEN syndromes (RET and
      MEN1) and syndromes with an endocrine tumor component (VHL and NF1). We report
      the fine mapping of the disease locus and the identification of a homozygous
      frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor
      p27(Kip1). As a consequence of the mutation, MENX-affected rats show dramatic
      reduction in p27(Kip1) protein. We have identified a germ-line nonsense mutation
      in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with
      pituitary and parathyroid tumors. Expanded pedigree analysis shows that the
      mutation is associated with the development of an MEN1-like phenotype in multiple
      generations. Our findings demonstrate that germ-line mutations in p27(Kip1) can
      predispose to the development of multiple endocrine tumors in both rats and
      humans.

PMID- 17030813
TI  - MicroRNAs and osmotic regulation.

PMID- 17030814
TI  - Angiopoietin-2 functions as an autocrine protective factor in stressed
      endothelial cells.
AB  - Angiopoietin (Ang)-2, a context-dependent agonist/antagonist for the vascular
      specific Tie2 receptor, is highly expressed by endothelial cells at sites of
      normal and pathologic angiogenesis. One prevailing model suggests that in these
      settings, Ang-2 acts as an autocrine Tie2 blocker, inhibiting the stabilizing
      influence of the Tie2 activator Ang-1, thereby promoting vascular remodeling.
      However, the effects of endogenous Ang-2 on cells that are actively producing it
      have not been studied in detail. Here, we demonstrate that Ang-2 expression is
      rapidly induced in endothelial cells by the transcription factor FOXO1 after
      inhibition of the phosphatidylinositol 3-kinase/Akt pathway. We employ RNAi and
      blocking antibodies to show that in this setting, Ang-2 unexpectedly functions as
      a Tie2 agonist, bolstering Akt activity so as to provide negative feedback on
      FOXO1-regulated transcription and apoptosis. In addition, we show that Ang-2,
      like Ang-1, activates Tie2/Akt signaling in vivo, thereby inhibiting the
      expression of FOXO1 target genes. Consistent with a role for Ang-2 as a Tie2
      activator, we demonstrate that Ang-2 inhibits vascular leak. Our data suggests a
      model in which Ang-2 expression is induced in stressed endothelial cells, where
      it acts as an autocrine Tie2 agonist and protective factor.

PMID- 17030815
TI  - Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell
      response to histone deacetylase inhibitor.
AB  - There is a great need to develop better mechanism-based therapies for prostate
      cancer. In this investigation, we studied four human prostate cancer cell lines,
      LNCaP, DU145, LAPC4, and PC3, which differ in response to the histone deacetylase
      inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug.
      Examining the role of intrinsic mitochondrial caspase-dependent apoptosis and
      caspase-independent, reactive oxygen species (ROS) facilitated cell death, has
      provided an understanding of mechanisms that may determine the varied response to
      the histone deacetylase inhibitor. We found striking differences among these
      cancer cells in constitutive expression and response to suberoylanilide
      hydroxamic acid in levels of antiapoptotic and proapoptotic proteins,
      mitochondria membrane integrity, activation of caspases, ROS accumulation, and
      expression of thioredoxin, the major scavenger of ROS. Identifying these
      differences can have predictive value in assessing therapeutic response and
      identifying targets to enhance therapeutic efficacy.

PMID- 17030812
TI  - The deepest divergences in land plants inferred from phylogenomic evidence.
AB  - Phylogenetic relationships among the four major lineages of land plants
      (liverworts, mosses, hornworts, and vascular plants) remain vigorously contested;
      their resolution is essential to our understanding of the origin and early
      evolution of land plants. We analyzed three different complementary data sets: a
      multigene supermatrix, a genomic structural character matrix, and a chloroplast
      genome sequence matrix, using maximum likelihood, maximum parsimony, and
      compatibility methods. Analyses of all three data sets strongly supported
      liverworts as the sister to all other land plants, and analyses of the multigene
      and chloroplast genome matrices provided moderate to strong support for hornworts
      as the sister to vascular plants. These results highlight the important roles of
      liverworts and hornworts in two major events of plant evolution: the water-to
      land transition and the change from a haploid gametophyte generation-dominant
      life cycle in bryophytes to a diploid sporophyte generation-dominant life cycle
      in vascular plants. This study also demonstrates the importance of using a
      multifaceted approach to resolve difficult nodes in the tree of life. In
      particular, it is shown here that densely sampled taxon trees built with multiple
      genes provide an indispensable test of taxon-sparse trees inferred from genome
      sequences.

PMID- 17030816
TI  - Transforming reflectance spectra into Munsell color space by using prime colors.
AB  - Independent researchers have proved mathematically that, given a set of color
      matching functions, there exists a unique set of three monochromatic spectral
      lights that optimizes luminous efficiency and color gamut. These lights are
      called prime colors. We present a method for transforming reflectance spectra
      into Munsell color space by using hypothetical absorbance curves based on
      Gaussian approximations of the prime colors and a simplified version of opponent
      process theory. The derived color appearance system is represented as a 3D color
      system that is qualitatively similar to a conceptual representation of the
      Munsell color system. We illustrate the application of the model and compare it
      with existing models by using reflectance spectra obtained from 1,269 Munsell
      color samples.

PMID- 17030817
TI  - Salmon-farming impacts on wild salmon.

PMID- 17030818
TI  - Pinoresinol: A lignol of plant origin serving for defense in a caterpillar.
AB  - Pinoresinol, a lignan of wide distribution in plants, is found to occur as a
      minor component in the defensive secretion produced by glandular hairs of
      caterpillars of the cabbage butterfly, Pieris rapae. The compound or a derivative
      is appropriated by the larva from its normal food plant (the cabbage, Brassica
      oleracea). Pinoresinol was shown to be absent from the secretion if the larva was
      given a cabbage-free diet but present in the effluent if that diet was
      supplemented with pinoresinol. Pinoresinol is shown to be a feeding deterrent to
      ants (Formica exsectoides), indicating that it can complement the defensive
      action of the primary components of the secretion, a set of previously reported
      lipids called mayolenes. In the test with F. exsectoides, pinoresinol proved to
      be more potent than concomitantly tested mayolene-16.

PMID- 17030819
TI  - Uncertainty in predictions of disease spread and public health responses to
      bioterrorism and emerging diseases.
AB  - Concerns over bioterrorism and emerging diseases have led to the widespread use
      of epidemic models for evaluating public health strategies. Partly because
      epidemic models often capture the dynamics of prior epidemics remarkably well,
      little attention has been paid to how uncertainty in parameter estimates might
      affect model predictions. To understand such effects, we used Bayesian statistics
      to rigorously estimate the uncertainty in the parameters of an epidemic model,
      focusing on smallpox bioterrorism. We then used a vaccination model to translate
      the uncertainty in the model parameters into uncertainty in which of two
      vaccination strategies would provide a better response to bioterrorism, mass
      vaccination, or vaccination of social contacts, so-called "trace vaccination."
      Our results show that the uncertainty in the model parameters is remarkably high
      and that this uncertainty has important implications for vaccination strategies.
      For example, under one plausible scenario, the most likely outcome is that mass
      vaccination would save approximately 100,000 more lives than trace vaccination.
      Because of the high uncertainty in the parameters, however, there is also a
      substantial probability that mass vaccination would save 200,000 or more lives
      than trace vaccination. In addition to providing the best response to the most
      likely outcome, mass vaccination thus has the advantage of preventing outcomes
      that are only slightly less likely but that are substantially more horrific.
      Rigorous estimates of uncertainty thus can reveal hidden advantages of public
      health strategies, suggesting that formal uncertainty estimation should play a
      key role in planning for epidemics.

PMID- 17030820
TI  - Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic
      effects.
AB  - A pluripotent cell line, C3H10T1/2, is induced to undergo adipogenesis by a
      mixture of factors that includes a glucocorticoid such as dexamethasone. We found
      that expression of myostatin (MSTN), a TGF-beta family member extensively studied
      in muscle, was induced by dexamethasone under those differentiation conditions.
      Moreover, MSTN could substitute for dexamethasone in the adipogenesis mixture.
      However, the adipocytes induced by MSTN in both cell culture and transgenic mice
      were small and expressed markers characteristic of immature adipocytes. These
      adipocytes exhibited cell-autonomous increases in insulin sensitivity and glucose
      oxidation. In mice, these effects produced elevated systemic insulin sensitivity
      and resistance to diet-induced obesity. Modulation of the final stages of
      adipogenesis may provide a novel approach to understanding and treating metabolic
      disease.

PMID- 17030821
TI  - A beta2-frequency (20-30 Hz) oscillation in nonsynaptic networks of somatosensory
      cortex.
AB  - Beta2 frequency (20-30 Hz) oscillations appear over somatosensory and motor
      cortices in vivo during motor preparation and can be coherent with muscle
      electrical activity. We describe a beta2 frequency oscillation occurring in vitro
      in networks of layer V pyramidal cells, the cells of origin of the corticospinal
      tract. This beta2 oscillation depends on gap junctional coupling, but it survives
      a cut through layer 4 and, hence, does not depend on apical dendritic
      electrogenesis. It also survives a blockade of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors or a blockade of GABA(A) receptors that is
      sufficient to suppress gamma (30-70 Hz) oscillations in superficial cortical
      layers. The oscillation period is determined by the M type of K+ current.

PMID- 17030822
TI  - Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the
      corticospinal tract.
AB  - Fine movement in the body is controlled by the motor cortex, which signals in a
      topographically specific manner to neurons in the spinal cord by means of the
      corticospinal tract (CST). How the correct topography of the CST is established
      is unknown. To investigate the possibility that the Eph tyrosine kinase receptor
      EphA4 is involved in this process, we have traced CST axons in mice in which the
      EphA4 gene has been deleted. The forelimb subpopulation of CST axons is
      unaffected in the EphA4-/- mice, but the hindlimb subpopulation branches too
      early within the cord, both temporally and spatially. EphA4 shows a dynamic
      expression pattern in the environment of the developing CST in the spinal cord:
      high at the time of forelimb branching and down-regulated before hindlimb
      branching. To examine whether the fore- and hindlimb subpopulations of CST axons
      respond differently to EphA4 in their environment, neurons from fore- and
      hindlimb motor cortex were cultured on a substrate containing EphA4. Neurons from
      the hindlimb cortex showed reduced branching on the EphA4 substrate compared with
      their forelimb counterparts. Neurons from the hindlimb cortex express ephrinA5, a
      high-affinity ligand for EphA4, at higher levels compared with forelimb cortex
      neurons, and this expression is down-regulated before hindlimb branching.
      Together, these findings suggest that EphA4 regulates topographic mapping of the
      CST by controlling the branching of CST axons in the spinal cord.

PMID- 17030823
TI  - An arsenic metallochaperone for an arsenic detoxification pump.
AB  - Environmental arsenic is a world-wide health issue, making it imperative for us
      to understand mechanisms of metalloid uptake and detoxification. The predominant
      intracellular form is the highly mephitic arsenite, which is detoxified by
      removal from cytosol. What prevents arsenite toxicity as it diffuses through
      cytosol to efflux systems? Although intracellular copper is regulated by
      metallochaperones, no chaperones involved in conferring resistance to other
      metals have been identified. In this article, we report identification of an
      arsenic chaperone, ArsD, encoded by the arsRDABC operon of Escherichia coli. ArsD
      transfers trivalent metalloids to ArsA, the catalytic subunit of an
      As(III)/Sb(III) efflux pump. Interaction with ArsD increases the affinity of ArsA
      for arsenite, thus increasing its ATPase activity at lower concentrations of
      arsenite and enhancing the rate of arsenite extrusion. Cells are consequently
      resistant to environmental concentrations of arsenic. This report of an arsenic
      chaperone suggests that cells regulate the intracellular concentration of
      arsenite to prevent toxicity.

PMID- 17030824
TI  - Divergent mtDNA lineages of goats in an Early Neolithic site, far from the
      initial domestication areas.
AB  - Goats were among the first farm animals domesticated, approximately 10,500 years
      ago, contributing to the rise of the "Neolithic revolution." Previous genetic
      studies have revealed that contemporary domestic goats (Capra hircus) show far
      weaker intercontinental population structuring than other livestock species,
      suggesting that goats have been transported more extensively. However, the timing
      of these extensive movements in goats remains unknown. To address this question,
      we analyzed mtDNA sequences from 19 ancient goat bones (7,300-6,900 years old)
      from one of the earliest Neolithic sites in southwestern Europe. Phylogenetic
      analysis revealed that two highly divergent goat lineages coexisted in each of
      the two Early Neolithic layers of this site. This finding indicates that high
      mtDNA diversity was already present >7,000 years ago in European goats, far from
      their areas of initial domestication in the Near East. These results argue for
      substantial gene flow among goat populations dating back to the early
      neolithisation of Europe and for a dual domestication scenario in the Near East,
      with two independent but essentially contemporary origins (of both A and C
      domestic lineages) and several more remote and/or later origins.

PMID- 17030825
TI  - The FDA and drug safety: a proposal for sweeping changes.
AB  - The current Food and Drug Administration (FDA) system of regulating drug safety
      has serious limitations and is in need of changes. The major problems include the
      following: the design of initial preapproval studies lets uncommon, serious
      adverse events go undetected; massive underreporting of adverse events to the FDA
      postmarketing surveillance system reduces the ability to quantify risk
      accurately; manufacturers do not fulfill the majority of their postmarketing
      safety study commitments; the FDA lacks authority to pursue sponsors who violate
      regulations and ignore postmarketing safety study commitments; the public
      increasingly perceives the FDA as having become too close to the regulated
      pharmaceutical industry; the FDA's safety oversight structure is suboptimal; and
      the FDA's expertise and resources in drug safety and public health are limited.
      To address these problems, we urge Congress, which is ultimately responsible for
      the FDA's performance, to implement the following 5 recommendations: (1) give the
      FDA more direct legal authority to pursue violations, (2) authorize the adoption
      of a conditional drug approval policy, at least for selected drugs, (3) provide
      additional financial resources to support the safety operations, (4) mandate a
      reorganization of the agency with emphasis on strengthening the evaluation and
      proactive monitoring of drug safety, and (5) require broader representation of
      safety experts on the FDA's advisory committees.

PMID- 17030826
TI  - Risk of acquiring antibiotic-resistant bacteria from prior room occupants.
AB  - BACKGROUND: Environmental contamination with methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant enterococci (VRE) occurs during the care
      of patients harboring these organisms and may increase the risk of transmission
      to subsequent room occupants. METHODS: Twenty-month retrospective cohort study of
      patients admitted to 8 intensive care units performing routine admission and
      weekly screening for MRSA and VRE. We assessed the relative odds of acquisition
      among patients admitted to rooms in which the most recent occupants were MRSA
      positive or VRE positive, compared with patients admitted to other rooms.
      RESULTS: Of 11 528 intensive care unit room stays, 10 151 occupants were eligible
      to acquire MRSA, and 10 349 were eligible to acquire VRE. Among patients whose
      prior room occupant was MRSA positive, 3.9% acquired MRSA, compared with 2.9% of
      patients whose prior room occupant was MRSA negative (adjusted odds ratio, 1.4; P
      = .04). VRE, Among patients whose prior room occupant was VRE positive, these
      values were 4.5% and 2.8% respectively (adjusted odds ratio, 1.4; P = .02). These
      excess risks accounted for 5.1% of all incident MRSA cases and 6.8% of all
      incident VRE cases, with a population attributable risk among exposed patients of
      less than 2% for either organism. Acquisition was significantly associated with
      longer post-intensive care unit length of stay. CONCLUSIONS: Admission to a room
      previously occupied by an MRSA-positive patient or a VRE-positive patient
      significantly increased the odds of acquisition for MRSA and VRE. However, this
      route of transmission was a minor contributor to overall transmission. The effect
      of current cleaning practices in reducing the risk to the observed levels and the
      potential for further reduction are unknown.

PMID- 17030827
TI  - High prevalence of stroke symptoms among persons without a diagnosis of stroke or
      transient ischemic attack in a general population: the REasons for Geographic And
      Racial Differences in Stroke (REGARDS) study.
AB  - BACKGROUND: A substantial portion of the general population has clinically silent
      stroke on brain imaging. These lesions may cause symptoms. This study assessed
      the prevalence of stroke symptoms in a stroke- and transient ischemic attack
      (TIA)-free population and the association of symptoms with risk factors indexed
      by the Framingham Stroke Risk Score. METHODS: We performed a cross-sectional
      analysis from a randomly sampled national cohort enrolled from January 25, 2003,
      through November 30, 2005, with oversampling from the southeastern stroke belt
      and African American populations. The main outcome measure was stroke symptoms
      assessed by validated questionnaire. RESULTS: The study included 18 462 (41%
      African American; 51% female; mean age, 65.8 years) participants who reported no
      stroke or TIA. The prevalence of stroke symptoms was 5.8% for sudden painless
      hemibody weakness, 8.5% for sudden hemibody numbness, 4.6% for sudden painless
      loss of vision in one or both eyes, 3.1% for sudden hemifield visual loss, 2.7%
      for sudden inability to understand speech, and 3.8% for sudden inability of
      linguistic expression. The prevalence of 1 or more symptoms was 17.8%. Relative
      to the first quartile of the Framingham Stroke Risk Score, the adjusted odds
      ratio for 1 or more stroke symptoms increased from 1.0 (95% confidence interval
      [CI], 0.90-1.2) in the second quartile to 1.2 (95% CI, 1.1-1.5) and 1.5 (95% CI,
      1.3-1.6) in successive quartiles. Symptoms were more prevalent among African
      American compared with white participants and among those with lower income,
      lower educational level, and fair to poor perceived health status. CONCLUSIONS:
      The general population without prior diagnosed stroke or TIA has a high
      prevalence of stroke symptoms. The relationship between symptoms and risk factors
      suggests that some symptomatic individuals may have had clinically undetected
      cerebrovascular events and may benefit from aggressive stroke prophylaxis.

PMID- 17030828
TI  - Lifetime cumulative exposure to secondhand smoke and risk of myocardial
      infarction in never smokers: results from the Western New York health study, 1995
      2001.
AB  - BACKGROUND: Although many epidemiologic studies have investigated the association
      between exposure to secondhand smoke (SHS) and risk of coronary heart disease
      (CHD), few of these studies have assessed exposure measures from different
      sources over a lifetime. Therefore, we sought to test the association between
      lifetime cumulative exposure to SHS and risk of myocardial infarction (MI) (as an
      indication of CHD) among never smokers. METHODS: A population-based case-control
      study in which participants were 1541 never smokers (284 cases and 1257 controls)
      drawn from 1197 women and men with incident MI and 2850 healthy controls (aged 35
      70 years) identified from 2 Western New York counties between 1995 and 2001.
      Study subjects were asked to report their exposure to SHS at home, at work, and
      in public settings from childhood to their present age. Exposure histories from
      each source were combined to form a cumulative lifetime exposure measure.
      Multiple logistic regression analysis estimated the association between SHS
      exposure and case status adjusted for age, sex, education, body mass index, race,
      drinking status, lifetime physical activity, hypertension, diabetes mellitus, and
      hypercholesterolemia. RESULTS: After adjustment for covariates, exposure to SHS
      was not significantly associated with an increased risk of MI. Compared with
      participants in the bottom tertile of SHS exposure, those in the top tertile had
      an odds ratio of 1.19 [95% confidence interval, 0.78-1.82] for MI. Virtually all
      subjects reported some exposure to SHS over their lifetime, but self-reported
      exposures declined over time, especially in the period closest to the interview.
      CONCLUSIONS: Exposure to SHS has declined sharply among nonsmokers in recent
      years. In the absence of high levels of recent exposure to SHS, cumulative
      lifetime exposure to SHS may not be as important a risk factor for MI as
      previously thought.

PMID- 17030829
TI  - Factors associated with dietary supplement use among prescription medication
      users.
AB  - BACKGROUND: We examined the patterns of nonvitamin dietary supplement (NVDS) use
      among adult prescription medication users in the United States. METHODS: Using
      the 2002 National Health Interview Survey, we analyzed factors associated with
      NVDS use and prescription medication use in the prior 12 months with descriptive,
      chi(2), and logistic regression analysis. RESULTS: In the United States, 21% of
      adult prescription medication users reported using NVDSs in the prior 12 months.
      Of the respondents who used both prescription medications and NVDSs in the prior
      12 months, 69% did not discuss this use with a conventional medical practitioner.
      Among adults who used prescription medications in the prior 12 months, the most
      commonly used supplements included echinacea, ginseng, ginkgo, garlic, and
      glucosamine chondroitin. Prescription medication users with menopause and chronic
      gastrointestinal disorders had the highest rates of NVDS use (33% and 28%,
      respectively), and prescription medication users with coronary heart disease and
      history of myocardial infarction had the lowest rates of use (12% each). In the
      adjusted analysis, factors associated with increased use of NVDSs by prescription
      medication users included being female, being Hispanic, having more years of
      education, living in the West, lacking medical insurance, and having chronic
      conditions. Elderly respondents were less likely to use NVDSs. CONCLUSION: One in
      4 prescription medication users took an NVDS in the prior 12 months, yet the
      majority did not share this with a conventional medical professional.

PMID- 17030830
TI  - Risk factors of vitamin B(12) deficiency in patients receiving metformin.
AB  - BACKGROUND: Identification of risk factors for metformin-related vitamin B(12)
      deficiency has major potential implications regarding the management of diabetes
      mellitus. METHODS: We conducted a nested case-control study from a database in
      which the source population consisted of subjects who had levels of both serum
      vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified
      155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to
      metformin treatment. Another 310 controls were selected from the cohort who did
      not have vitamin B(12) deficiency while taking metformin. RESULTS: A total of 155
      patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum
      vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were
      compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]).
      After adjusting for confounders, we found clinically important and statistically
      significant association of vitamin B(12) deficiency with dose and duration of
      metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of
      2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency
      (P<.001). Among those using metformin for 3 years or more, the adjusted odds
      ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with
      those receiving metformin for less than 3 years. After exclusion of 113 subjects
      with borderline vitamin B(12) concentration, dose of metformin remained the
      strongest independent predictor of vitamin B(12) deficiency. CONCLUSIONS: Our
      results indicate an increased risk of vitamin B(12) deficiency associated with
      current dose and duration of metformin use despite adjustment for many potential
      confounders. The risk factors identified have implications for planning screening
      or prevention strategies in metformin-treated patients.

PMID- 17030831
TI  - Annual influenza vaccination in community-dwelling elderly individuals and the
      risk of lower respiratory tract infections or pneumonia.
AB  - BACKGROUND: Influenza vaccination has been associated with a reduction in the
      number of hospitalizations for respiratory conditions in elderly persons over the
      period from 1996 to 2002. Little is known, however, about the effect of influenza
      vaccination on the whole range of severity of respiratory tract infections.
      METHODS: We investigated the effect of annual influenza vaccination on the
      occurrence of lower respiratory tract infections (LRTIs) in community-dwelling
      elderly individuals. From 1996 to 2002, we performed a population-based cohort
      study, using the computerized Integrated Primary Care Information database in the
      Netherlands, of community-dwelling subjects who were 65 years or older on January
      1 of the year of study entry. For each year, the individual cumulative exposure
      to influenza vaccination since study entry was computed. We compared the risk of
      LRTI after a first vaccination or revaccination with the risk for no vaccination
      using a time-varying multivariate Cox proportional hazard model, adjusted for
      age, sex, smoking, and underlying disease. RESULTS: In the study population of 26
      071 subjects, 3412 developed LRTIs during follow-up. During the influenza
      epidemic periods, a first vaccination did not reduce risk for LRTI. In the total
      population, the hazard ratio following a first vaccination was 0.86 (95%
      confidence interval [CI], 0.71 to 1.05); in the population without or with
      comorbidity, these ratios were 0.90 (95% CI, 0.56 to 1.45) and 0.83 (95% CI, 0.66
      to 1.04), respectively. During epidemic periods, revaccination reduced risk of
      LRTI by 33% (95% CI, 8% to 52%) in individuals without comorbidity. In
      individuals with comorbidity, the risk reduction of 5% was nonsignificant (95%
      CI, -10% to 18%). CONCLUSION: In this study, annual influenza revaccination was
      associated with a reduction in LRTI in community-dwelling elderly individuals.

PMID- 17030832
TI  - Lower extremity nerve function in patients with lower extremity ischemia.
AB  - BACKGROUND: We determined whether lower extremity ischemia, as measured by the
      ankle brachial index (ABI), is associated with impaired lower extremity nerve
      function. METHODS: Participants included 478 persons with peripheral arterial
      disease (PAD) identified from noninvasive vascular laboratories and 292 persons
      without PAD identified from a general medicine practice and noninvasive vascular
      laboratories. Peripheral arterial disease was defined as an ABI lower than 0.90
      (mild PAD: ABI, 0.70 to <0.90; moderate PAD: ABI, 0.50 to <0.70; and severe PAD:
      ABI, <0.50). The ABI and electrophysiologic measures of the peroneal, sural, and
      ulnar nerves were obtained. RESULTS: Among 546 participants without diabetes, PAD
      participants had significantly impaired peripheral nerve function in the upper
      and lower extremities compared with non-PAD participants. After adjusting for
      age, sex, race, smoking, height, body mass index, recruitment source, alcohol
      use, disk disease, spinal stenosis, cardiac disease, and cerebrovascular disease,
      these associations were not statistically significant. After adjusting for
      confounders among nondiabetic participants, those with severe PAD (ABI, <0.50)
      had poorer peroneal nerve conduction velocity (NCV) compared with participants
      without PAD (42.6 vs 44.8 m/s; P = .003) and poorer peroneal NCV compared with
      participants with mild PAD (42.6 vs 45.0 m/s; P = .001) or moderate PAD (42.6 vs
      44.1 m/s; P = .03). Among 224 participants with diabetes, after adjusting for
      confounders, PAD was associated with poorer peroneal NCV (40.8 vs 43.5 m/s; P =
      .01), sural nerve amplitude (3.1 vs 4.8 muV; P = .045), and ulnar NCV (47.6 vs
      50.2 m/s; P = .03) compared with those without PAD. CONCLUSIONS: Our findings
      suggest that leg ischemia impairs peroneal nerve function. This association is
      less strong in patients with diabetes, perhaps because of the overriding
      influence of diabetes on peripheral nerve function. Clinicians should consider
      screening for PAD in patients with idiopathic peroneal nerve dysfunction.
      Peripheral arterial disease-associated nerve dysfunction may contribute to PAD
      associated functional impairment.

PMID- 17030833
TI  - Brain dysfunction: another burden for the chronically critically ill.
AB  - BACKGROUND: Chronic critical illness is a devastating syndrome of prolonged
      respiratory failure and other derangements. To our knowledge, no previous
      research has addressed brain dysfunction in the chronically critically ill,
      although this topic is important for medical decision making. METHODS: We studied
      a prospective cohort of 203 consecutive, chronically critically ill adults
      transferred to our hospital's respiratory care unit (RCU) after tracheotomy for
      failure to wean. We measured prevalence and duration of coma and delirium during
      RCU treatment using the Confusion Assessment Method for the Intensive Care Unit
      with the Richmond Agitation-Sedation Scale. To assess survivors (at 3 and 6
      months after RCU discharge), we used a validated telephone Confusion Assessment
      Method. RESULTS: Before hospitalization, most (153 [75.4%]) of the 203 patients
      in the study were at home, completely independent (115 [56.7%]), and cognitively
      intact (116 [82.0%]). In the RCU, 61 (30.0%) were comatose throughout the stay.
      Approximately half of patients (66 of 142) who were not in coma were delirious.
      Patients spent an average of 17.9 days (range, 1-153 days) in coma or delirium
      (average RCU stay, 25.6 days). Half of survivors (79 of 160) had one of these
      disturbances at RCU discharge. At 6 months, three fourths (151) of the study
      patients were dead or institutionalized; of 85 survivors, 58 (68.2%) were too
      profoundly impaired to respond to telephone cognitive assessment, and 53 (62.4%)
      were dependent in all activities of daily living. CONCLUSIONS: Severe, prolonged,
      and permanent brain dysfunction is a prominent feature of chronic critical
      illness. These data, together with previous reports of symptom distress and rates
      of mortality and institutionalization, describe burdens for chronically
      critically ill patients receiving continued life-prolonging treatment and for
      their families.

PMID- 17030834
TI  - Quality-of-life impact and treatment of urinary incontinence in ethnically
      diverse older women.
AB  - OBJECTIVE: To identify the factors associated with greater quality-of-life
      impact, treatment seeking, and use of treatments for urinary incontinence in
      ethnically diverse older women. METHODS: Cross-sectional analysis of a population
      based cohort of 2109 middle-aged and older women who were randomly selected from
      age and race/ethnicity strata. Data were collected by self-report questionnaires
      and in-person interviews. Multivariable logistic regression was used to identify
      predictors of high quality-of-life impact (Incontinence Impact Questionnaire
      [IIQ] score > or =75th percentile), treatment seeking, and use of treatments for
      incontinence. RESULTS: More than one fourth (n = 603) of the study participants
      (including 96 black [16%], 123 Latina [20%], 65 Asian [11%], and 309 white [51%]
      women) reported weekly incontinence. After clinical severity and other factors
      were adjusted for, women were more likely to experience high quality-of-life
      impact if they had nighttime incontinence (odds ratio [OR], 2.5; 95% confidence
      interval [CI], 1.3-4.9), coital incontinence (OR, 1.9; 95% CI, 1.1-3.3), or
      comorbid fecal incontinence (OR, 2.2; 95% CI, 1.2-4.2). Predictors of treatment
      seeking included older age (OR, 1.6 per 10 years; 95% CI, 1.2-2.0); higher IIQ
      score (OR, 4.6 for highest IIQ quartile vs lowest IIQ quartile; 95% CI, 2.5-8.4),
      and higher household income (OR, 2.6 for income > or = US dollars 100 000/y vs <
      US dollars 20 000/y; 95% CI, 1.0-2.7). CONCLUSIONS: Clinicians seeking to
      evaluate the impact of incontinence on women's lives should assess not only the
      clinical severity of their symptoms but also the specific context in which
      symptoms occur. The prevalence of treatment seeking for incontinence is low
      across all ethnic groups, even when women have clinically severe symptoms and
      access to a health provider.

PMID- 17030835
TI  - Mannose-binding lectin and mortality in type 2 diabetes.
AB  - BACKGROUND: Inflammation and complement activation initiated by mannose-binding
      lectin (MBL) may be implicated in the pathogenesis of diabetic vascular
      complications. We evaluated the relationship between serum MBL and mortality and
      development of albuminuria in type 2 diabetes. METHODS: Levels of MBL and C
      reactive protein (CRP) were measured at baseline in 326 patients with type 2
      diabetes who attended the Steno Diabetes Center, Gentofte, Denmark, for control.
      Urinary albumin excretion was determined annually, and the vital status of all
      patients was traced after more than 15 years of follow-up. RESULTS: During follow
      up, 169 patients died. The risk of dying was significantly higher among patients
      with MBL levels greater than or equal to 1000 microg/L than among patients with
      levels less than 1000 microg/L (hazard ratio, 1.5; 95% confidence interval, 1.1
      2.1; P = .005). After adjustment for known confounders, MBL remained a
      significant risk factor for death from any cause. It added to the predictive
      power of CRP, and mortality was significantly higher among patients with both
      high MBL (> or =1000 microg/L) and high CRP (above the median, 3.6 mg/L) levels
      than among patients with both low MBL and low CRP levels (hazard ratio, 2.7; 95%
      confidence interval, 1.7-4.3; P<.001). Normoalbuminuric patients with both high
      MBL and high CRP levels at baseline had a significantly increased risk of
      developing microalbuminuria or macroalbuminuria compared with patients with both
      low MBL and low CRP levels (hazard ratio, 2.6; 95% confidence interval, 1.5-4.4;
      P<.001). CONCLUSION: In patients with type 2 diabetes, measurements of MBL alone
      or in combination with CRP can provide prognostic information on mortality and
      the development of albuminuria.

PMID- 17030836
TI  - Impact of chronic kidney disease on health-related quality-of-life improvement
      after coronary artery bypass surgery.
AB  - BACKGROUND: Little is known about the impact of chronic kidney disease (CKD) on
      health-related quality-of-life outcomes after coronary artery bypass grafting
      (CABG). METHODS: Our objective was to examine the changes in physical function
      (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without
      CKD. The primary end points were mean change in score and status of "improved" or
      "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form
      36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD
      stage (0-5). RESULTS: Absolute PF and MH scores at baseline and at 6 months
      varied by renal impairment level. Patients with severe CKD (stages 4-5) had a
      mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in
      the rest of the cohort (P<.001). After adjustment for baseline score, 21% of
      patients with advanced CKD experienced worsened PF scores, compared with 0% of
      patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores,
      patients with and without CKD had similar improvements in mean MH scores at 6
      months, and patients with stages 4 to 5 CKD had the highest frequency of those
      with improved MH scores (77%). After adjustment, no patients experienced worsened
      MH scores. CONCLUSIONS: After 6 months, patients with severe CKD who underwent
      CABG had improvement in MH but not improvement in PF and may have had worsened PF
      compared with those without severe CKD. Comparable evidence regarding quality-of
      life outcomes in the absence of CABG is needed to more fully inform decision
      making regarding patients with severe CKD and coronary artery disease.

PMID- 17030837
TI  - An evaluation of screening questions for childhood abuse in 2 community samples:
      implications for clinical practice.
AB  - BACKGROUND: A number of practice guidelines and recommendations call for the
      assessment of childhood abuse in adult medical patients, but none specifies how
      best to do this. The objective of this study was to use evidence from 2 community
      based population samples to evaluate abuse-screening questions that are often
      asked in medical clinics and to identify a small set of questions to improve
      screening practices. METHODS: The Childhood Trauma Questionnaire-Short Form (CTQ
      SF) was administered in 2 randomized telephone interview surveys with adults aged
      18 to 65 years. RESULTS: A total of 880 (2003 survey) and 998 (1997 survey)
      respondents completed the CTQ-SF in the 2 surveys. In both surveys, the rates of
      physical (16% and 15%), emotional (31% and 29%), and sexual (10% and 9%) abuse
      elicited using 3 behaviorally descriptive items in each abuse category were
      approximately twice the rates elicited using the explicit labeling terms
      physically abused (8% and 8%), emotionally abused (15% and 13%), or sexually
      abused (5% and 5%) (P<.001 for each). Inquiries explicitly using the labeling
      term abuse successfully identified a low percentage of respondents who reported
      behaviorally described abusive experiences for each type of abuse (34%-51%). In
      addition, after adjustment for the number and frequency of abusive experiences in
      both surveys, women were more likely than men to label themselves as explicitly
      abused for any abuse (odds ratio [OR], 1.7; P = .11 and OR, 2.8; P<.01), physical
      abuse (OR, 2.1; P = .14 and OR, 2.9; P<.01), emotional abuse (OR, 2.7; P<.01 and
      OR, 3.3; P<.01), and sexual abuse (OR, 3.5; P = .08 and OR, 1.5; P = .55).
      CONCLUSION: Inquiries about childhood abuse that use broad labeling questions
      identify a substantially smaller number of patients than behaviorally specific
      questions and may be less effective in initial screening for a history of abuse.

PMID- 17030838
TI  - Recent trends in the care of patients with non-ST-segment elevation acute
      coronary syndromes: insights from the CRUSADE initiative.
AB  - BACKGROUND: The extent to which national health quality improvement initiatives
      have altered reported treatment gaps among patients with non-ST-segment elevation
      acute coronary syndromes (NSTE ACS) is unknown. We sought to determine recent
      trends in adherence to guideline-based therapies for NSTE ACS. METHODS: We
      evaluated the treatment of patients with high-risk (positive cardiac markers
      and/or ischemic ST-segment changes) NSTE ACS enrolled in the Can Rapid Risk
      Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early
      Implementation of the ACC/AHA (American College of Cardiology/American Heart
      Association) Guidelines (CRUSADE) Quality Improvement Initiative from 2002
      through 2004 (a total of 113 595 patients over 11 calendar quarters). We analyzed
      adherence to guideline-recommended therapies, including medications used in the
      acute care period (<24 hours after presentation), invasive procedures, in
      hospital outcomes, and discharge therapies and interventions. RESULTS: The use of
      each class I guideline recommendation, as well as overall adherence to the
      guidelines, improved significantly (P<.001) during the study period. In the acute
      care setting, the use of antiplatelet agents increased by 5% and beta-blockers by
      12%; at hospital discharge, the use of antiplatelet agents increased by 3% and
      beta-blockers by 8%. Heparin use in the acute care period increased by 6%,
      largely owing to a 9% increase in the use of low-molecular-weight heparin. Use of
      glycoprotein IIb/IIIa inhibitors in the acute care period also increased by more
      than 13%. At discharge, clopidogrel use increased by 22%, lipid-lowering agents
      by 11%, and angiotensin-converting enzyme inhibitors by 5%. While adherence
      improved, many patients still failed to receive 100% indicated treatments at the
      end of the study period. CONCLUSIONS: During the 4 years since the initial
      release of the ACC/AHA guidelines for NSTE ACS, adherence to class I
      recommendations has significantly improved among hospitals participating in
      CRUSADE. Still, further improvements are needed for optimal implementation of the
      these guidelines.

PMID- 17030839
TI  - Time course of depression and outcome of myocardial infarction.
AB  - BACKGROUND: Depression predicts worse outcomes after myocardial infarction (MI),
      but whether its time course in the month following MI has prognostic importance
      is unknown. Our objective was to evaluate the prognostic importance of transient,
      new, or persistent depression on outcomes at 6 months after MI. METHODS: In a
      prospective registry of acute MI (Prospective Registry Evaluating outcomes after
      Myocardial Infarction: Events and Recovery [PREMIER]), depressive symptoms were
      measured in 1873 patients with the Patient Health Questionnaire (PHQ) during
      hospitalization and 1 month after discharge and were classified as transient
      (only at baseline), new (only at 1 month), or persistent (at both times).
      Outcomes at 6 months included (1) all-cause rehospitalization or mortality and
      (2) health status (angina, physical limitation, and quality of life using the
      Seattle Angina Questionnaire). RESULTS: Compared with nondepressed patients, all
      categories of depression were associated with higher rehospitalization or
      mortality rates, more frequent angina, more physical limitations, and worse
      quality of life. The adjusted hazard ratios for rehospitalization or mortality
      were 1.34, 1.71, and 1.42 for transient, new, and persistent depression,
      respectively (all P<.05). Corresponding odds ratios were 1.62, 2.73, and 2.64
      (all P<.01) for angina and 1.69, 2.25, and 3.27 (all P<.05) for physical
      limitation. Depressive symptoms showed a stronger association with health status
      compared with traditional measures of disease severity. CONCLUSION: Depressive
      symptoms after MI, irrespective of whether they persist, subside, or newly
      develop in the first month after hospitalization, are associated with worse
      outcomes after MI.

PMID- 17030840
TI  - Acquired hydrocephalus caused by a variant lymphocytic choriomeningitis virus.

PMID- 17030841
TI  - Ignoring study design heterogeneity in meta-analyses.

PMID- 17030842
TI  - Morphine is not a sedative and does not shorten life.

PMID- 17030843
TI  - Protecting the health of the public--Institute of Medicine recommendations on
      drug safety.

PMID- 17030844
TI  - Blueprint for a stronger Food and Drug Administration.

PMID- 17030845
TI  - Chimeric Japanese encephalitis virus/dengue 2 virus infectious clone: biological
      properties, immunogenicity and protection against dengue encephalitis in mice.
AB  - A molecular clone of Japanese encephalitis virus (JE virus) was derived from the
      JE virus Nakayama strain and used to produce infectious JE virus in cell culture.
      The engineered JE virus resembled the parental JE virus in cell-culture
      properties and was related closely to other JE virus strains based on nucleotide
      sequence analysis. The JE virus clone was used as a genetic background for
      construction of a chimeric virus containing the structural proteins prM and E of
      Dengue virus, serotype 2. The chimeric JE/dengue 2 virus generated authentic
      dengue 2 structural proteins as assessed by immunoassays for the dengue E
      protein. It exhibited a small plaque size and less efficient growth in various
      cell lines than the parental JE virus. JE/dengue 2 virus was non-neuroinvasive
      for young adult mice, but displayed partial neurovirulence at doses up to 4 log
      p.f.u. given intracerebrally. Immunization of 3-week-old mice with JE/dengue 2
      virus yielded neutralizing-antibody titres against dengue 2 virus and conferred
      protection against dengue encephalitis caused by neuroadapted dengue 2 virus. A
      rise in post-challenge neutralizing-antibody titres against dengue 2 virus in
      surviving mice suggests that immunization is associated with establishment of a
      memory antibody response in this model. This study demonstrates the capacity of
      JE virus to serve as a vector for expression of heterologous flavivirus
      structural proteins. Similar to previous studies with other chimeric
      flaviviruses, this approach may be useful as a genetic system for engineering
      experimental vaccines against Dengue virus and other medically important
      flaviviruses.

PMID- 17030846
TI  - PrP genotypes of atypical scrapie cases in Great Britain.
AB  - Great Britain and elsewhere have detected atypical scrapie infection in sheep
      with PrP genotypes thought to be genetically resistant to the classical form of
      scrapie. DNA sequencing of the PrP gene of British atypical scrapie cases (n=69),
      classical scrapie cases (n=59) and scrapie-free controls (n=138) was undertaken
      to identify whether PrP variants, other than the three well-characterized
      polymorphic codons, influenced susceptibility to atypical scrapie infection. Four
      non-synonymous changes, M112T, M137T, L141F and P241S, were detected that are
      most probably associated with the A(136)R(154)Q(171) haplotype. Only the PrP
      variant containing a phenylalanine residue at amino acid position 141 was found
      to be associated more commonly with the atypical scrapie cases. In addition to
      the single nucleotide polymorphisms associated with the ARQ allele, two out of
      nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24
      bp insertion, leading to an additional octapeptide repeat. In terms of PrP
      genetics, one classification of the GB scrapie cases examined in this study would
      place animals carrying any homozygous or heterozygous combination of ARR, AHQ or
      AF(141)RQ alleles, or any one of these alleles when paired with ARQ, as being
      susceptible to atypical scrapie infection, and animals heterozygous or homozygous
      for VRQ or homozygous for ARQ as being susceptible to classical scrapie disease.
      The AHQ PrP allele was associated with the highest incidence of atypical scrapie
      (263 per 100 000 alleles), whilst VRQ was associated with the lowest incidence
      (10 per 100 000 alleles).

PMID- 17030847
TI  - Adenovirus type 5 fiber knob domain has a critical role in fiber protein
      synthesis and encapsidation.
AB  - Adenovirus serotype 5 (Ad5) vectors carrying knobless fibers designed to remove
      their natural tropism were found to have a lower fiber content than recombinant
      Ad5 with wild-type (WT) capsid, implying a role for the knob-coding sequence
      or/and the knob domain in fiber encapsidation. Experimental data using a variety
      of fiber gene constructs showed that the defect did not occur at the fiber mRNA
      level, but at the protein level. Knobless fiber proteins were found to be
      synthesized at a significant slower rate compared with knob-carrying fibers, and
      the trimerization process of knobless fibers paralleled their slow rate of
      synthesis. A recombinant Ad5 diploid for the fiber gene (referred to as Ad5/R7
      ZZ(wt)/E1 : WT-fiber) was constructed to analyse the possible rescue of the
      knobless low-fiber-content phenotype by co-expression of WT fiber. Ad5/R7
      ZZ(wt)/E1 : WT-fiber contained a knobless fiber gene in its natural location (L5)
      in the viral genome and an additional WT fiber gene in an ectopic position in E1.
      Knobless fiber was still synthesized at low levels compared with the co-expressed
      E1 : WT fiber and the recovery of the two fiber species in virus progeny
      reflected their respective amounts in the infected cells. Our results suggested
      that deletion of the fiber knob domain had a negative effect on the translation
      of the fiber mRNA and on the intracellular concentration of fiber protein. They
      also suggested that the knob control of fiber protein synthesis and encapsidation
      occurred as a cis effect, which was not modified by WT fiber protein provided in
      trans by the same Ad5 genome.

PMID- 17030848
TI  - Adenovirus RID complex enhances degradation of internalized tumour necrosis
      factor receptor 1 without affecting its rate of endocytosis.
AB  - The receptor internalization and degradation (RID) complex of adenovirus plays an
      important role in modulating the immune response by downregulating the surface
      levels of tumour necrosis factor receptor 1 (TNFR1), thereby inhibiting NF-kappaB
      activation. Total cellular content of TNFR1 is also reduced in the presence of
      RID, which can be inhibited by treatment with lysosomotropic agents. In this
      report, surface biotinylation experiments revealed that, although RID and TNFR1
      were able to form a complex on the cell surface, the rate of TNFR1 endocytosis
      was not affected by RID. However, the degradation of internalized TNFR1 was
      enhanced significantly in the presence of RID. Therefore, these data suggest that
      RID downregulates TNFR1 levels by altering the fate of internalized TNFR1 that
      becomes associated with RID at the plasma membrane, probably by promoting its
      sorting into endosomal/lysosomal degradation compartments.

PMID- 17030849
TI  - The CR4 region of EBNA2 confers viability of Epstein-Barr virus-transformed B
      cells by CBF1-independent signalling.
AB  - The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene product is the key
      regulator of the latent genes of EBV and essential for EBV-mediated
      transformation of human primary B cells. Viral mutants were constructed carrying
      a deletion of the EBNA2 conserved region 4 (CR4). Primary resting B cells
      infected with the DeltaCR4-EBNA2 mutant virus were dramatically impaired for B
      cell transformation. Lymphoblastoid cell lines (LCLs) established with this
      mutant EBV revealed a prolonged population doubling time when cells were
      cultivated at low cell densities, which are not critical for wild-type-infected
      cells. Low-level spontaneous cell death occurred when the cells were cultivated
      at suboptimal cell densities. The phenotype of B cells and LCLs infected with the
      DeltaCR4-EBNA2 mutant virus indicated that the CR4 region of EBNA2 specifically
      contributes to the viability of the cells rather than affecting cell division
      rates.

PMID- 17030850
TI  - Maturation and function of human dendritic cells are inhibited by orf virus
      encoded interleukin-10.
AB  - Orf virus (ORFV) is a parapoxvirus that infects sheep, goats and man. In humans,
      the virus induces acute, pustular skin lesions that can develop into a
      progressive disease. Humans are susceptible to reinfection with ORFV and rare
      cases of persistent infection have been reported. ORFV encodes several
      immunomodulators, including a homologue of interleukin-10 (ORFV IL-10), that may
      explain these phenomena. The immunosuppressive effects of ORFV IL-10 on immature
      human dendritic cells (DCs) cultured from blood-derived monocytes (MoDCs) were
      investigated. MoDCs exposed simultaneously to lipopolysaccharide and ORFV IL-10
      showed enhanced ovalbumin-FITC uptake and reduced IL-12 expression, indicating
      inhibition of maturation. Moreover, ORFV IL-10 inhibited the upregulation of DC
      cell-surface activation and maturation markers MHC II, CD80, CD83 and CD86 and
      inhibited the capacity of MoDCs to activate CD4(+) T cells in an oxidative
      mitogenesis assay. These findings suggest that ORFV IL-10 may influence the
      development of acquired immunity in humans by impairing DC function.

PMID- 17030851
TI  - Human papillomaviruses target the double-stranded RNA protein kinase pathway.
AB  - The double-stranded RNA protein kinase (PKR) pathway plays a vital role in the
      innate immune response to viral infection. Activation of PKR following virus
      entry can lead to a shutdown in translation, thereby inhibiting viral protein
      synthesis and replication. Little is currently known about whether human
      papillomaviruses (HPVs) modulate PKR expression and activity. In this study,
      normal human foreskin keratinocytes (NHKs) transfected stably with the HPV 31 or
      16 genomes and cell lines expressing the HPV 16 E6 and E7 oncoproteins were used
      to examine effects on the PKR pathway. HPV gene products were found to modulate
      PKR phosphorylation, activity and localization. The levels of total PKR protein
      were reduced modestly in cells that maintained HPV 16 or 31 episomes through a
      reduction in PKR transcription. However, levels of phosphorylated PKR were
      decreased 4-fold through a post-transcriptional mechanism mediated by E6 and E7
      that was independent of the transcriptional downregulation mediated by HPV. In
      response to infection by vesicular stomatitis virus, phosphorylation of eIF2alpha
      was blocked in cells expressing HPV oncoproteins, but not in NHKs. Finally, it
      was observed that the cellular localization of PKR was altered by HPV gene
      products in HPV raft cultures, as well as HPV-positive patient biopsies. This
      effect was mediated by the HPV E6 oncoprotein and leads to the co-localization of
      PKR with P-bodies. These studies demonstrate that high-risk HPVs target the PKR
      pathway by multiple mechanisms.

PMID- 17030852
TI  - Papillomavirus in healthy skin of Australian animals.
AB  - Papillomaviruses are a group of ubiquitous viruses that are often found in normal
      skin of humans, as well as a range of different vertebrates. In this study, swab
      samples collected from the healthy skin of 225 Australian animals from 54 species
      were analysed for the presence of papillomavirus DNA with the general skin
      papillomavirus primer pair FAP59/FAP64. A total of five putative and potential
      new animal papillomavirus types were identified from three different animal
      species. The papillomaviruses were detected in one monotreme and two marsupial
      species: three from koalas, and one each from an Eastern grey kangaroo and an
      echidna. The papillomavirus prevalence in the three species was 14 % (10/72) in
      koalas, 20 % (1/5) in echidnas and 4 % (1/23) in Eastern grey kangaroos.
      Phylogenetic analysis was performed on the putative koala papillomavirus type
      that could be cloned and it appears in the phylogenetic tree as a novel putative
      papillomavirus genus. The data extend the range of species infected by
      papillomaviruses to the most primitive mammals: the monotremes and the
      marsupials.

PMID- 17030853
TI  - Identification of a genomic subgroup of BK polyomavirus spread in European
      populations.
AB  - BK polyomavirus (BKV) is highly prevalent in the human population, infecting
      children without obvious symptoms and persisting in the kidney in a latent state.
      In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV
      isolates worldwide are classified into four serologically distinct subtypes, I
      IV, with subtype I being the most frequently detected. Furthermore, subtype I is
      subdivided into subgroups based on genomic variations. In this study, the
      distribution patterns of the subtypes and subgroups of BKV were compared among
      four patient populations with various immunosuppressive states and of various
      ethnic backgrounds: (A) Finnish renal-transplant recipients; (B) Irish/English
      haematopoietic stem-cell transplant recipients with and without haemorrhagic
      cystitis; (C) Japanese renal-transplant recipients; and (D) Japanese bone-marrow
      transplant recipients. The typing sequences (287 bp) of BKV in population A were
      determined in this study; those in populations B-D have been reported previously.
      These sequences were subjected to phylogenetic and single nucleotide polymorphism
      analyses. Based on the results of these analyses, the BKV isolates in the four
      patient populations were classified into subtypes and subgroups. The incidence of
      subtype IV varied significantly among patient populations. Furthermore, the
      incidence of subgroup Ib-2 within subtype I was high in populations A and B,
      whereas that of Ic was high in populations C and D (P<0.01). These results
      suggest that subgroup Ib-2 is widespread among Europeans, whereas Ic is unique to
      north-east Asians. Furthermore, a phylogenetic analysis based on complete BKV DNA
      sequences supported the hypothesis that there is geographical separation of
      European and Asian BKV strains.

PMID- 17030854
TI  - Parvoviral nuclear import: bypassing the host nuclear-transport machinery.
AB  - The parvovirus Minute virus of mice (MVM) is a small DNA virus that replicates in
      the nucleus of its host cells. However, very little is known about the mechanisms
      underlying parvovirus' nuclear import. Recently, it was found that microinjection
      of MVM into the cytoplasm of Xenopus oocytes causes damage to the nuclear
      envelope (NE), suggesting that the nuclear-import mechanism of MVM involves
      disruption of the NE and import through the resulting breaks. Here, fluorescence
      microscopy and electron microscopy were used to examine the effect of MVM on host
      cell nuclear structure during infection of mouse fibroblast cells. It was found
      that MVM caused dramatic changes in nuclear shape and morphology, alterations of
      nuclear lamin immunostaining and breaks in the NE of infected cells. Thus, it
      seems that the unusual nuclear-import mechanism observed in Xenopus oocytes is in
      fact used by MVM during infection of host cells.

PMID- 17030855
TI  - Porcine circovirus type 2 replicase binds the capsid protein and an intermediate
      filament-like protein.
AB  - Porcine circovirus type 2 (PCV2) is an important porcine pathogen that
      establishes persistent subclinical infections but may, on activation, contribute
      to the development of post-weaning multisystemic wasting syndrome (PMWS). This
      disease is characterized by weight loss, respiratory or digestive disorders and
      enlarged lymph nodes with lymphocyte depletion. The molecular mechanisms behind
      the development of the disease are completely unknown. In order to clarify
      functions of the different viral proteins and, if possible, to connect these new
      findings to molecular mechanisms behind the pathogenesis or the viral life cycle,
      a bacterial two-hybrid screening of a porcine expression library from PK-15A
      cells was conducted. Using viral proteins corresponding to ORFs 1, 2, 3 and 4 as
      bait, a number of interactions were identified and two of them were chosen for
      further characterization. GST pull-down assays confirmed that viral replicase
      (Rep) interacted with an intermediate filament protein, similar to human
      syncoilin, and with the transcriptional regulator c-myc. Furthermore,
      interactions of the viral proteins to each other revealed an interaction between
      PCV2 Rep and the capsid (Cap) protein and Cap to itself.

PMID- 17030856
TI  - Rise in gamma interferon expression during resolution of duck hepatitis B virus
      infection.
AB  - Gamma interferon (IFN-gamma) expression plays a crucial role in the control of
      mammalian hepatitis B virus (HBV) infection. However, the role of duck INF-gamma
      (DuIFN-gamma) in the outcome of duck HBV (DHBV) infection, a reference model for
      hepadnavirus replication studies, has not yet been investigated. This work
      explored the dynamics of DuIFN-gamma expression in liver and peripheral blood
      mononuclear cells (PBMCs) during resolution of DHBV infection in adolescent ducks
      in relation to serum and liver markers of virus replication, histological changes
      and humoral response induction. DHBV infection of 3-week-old ducks resulted in
      transient expression of intrahepatic preS protein (days 3-14) and mild
      histological changes. Low-level viraemia was detected only during the first 10
      days of infection and was accompanied by early anti-preS antibody response
      induction. Importantly, a strong increase in intrahepatic DuIFN-gamma RNA was
      detected by real-time RT-PCR at days 6-14, which coincided with a sharp decrease
      in both viral DNA and preS protein in the liver. Interestingly, liver DuIFN-gamma
      expression remained augmented to the end of the follow-up period (day 66) and
      correlated with portal lymphocyte infiltration and persistence of trace
      quantities of intrahepatic DHBV DNA in animals that had apparently completely
      resolved the infection. Moreover, in infected ducks, a moderate increase was
      detected in the levels of DuIFN-gamma in PBMCs (days 12-14), which coincided with
      the peak in liver DuIFN-gamma RNA levels. These data reveal that increased DuIFN
      gamma expression in liver and PBMCs is concomitant with viral clearance,
      characterizing the resolution of infection, and provide new insights into the
      host-virus interactions that control DHBV infection.

PMID- 17030857
TI  - Genome of the most widely used viral biopesticide: Anticarsia gemmatalis multiple
      nucleopolyhedrovirus.
AB  - The genome of Anticarsia gemmatalis multiple nucleopolyhedrovirus isolate 2D
      (AgMNPV-2D), which is the most extensively used virus pesticide in the world, was
      completely sequenced and shown to have 132 239 bp (G+C content 44.5 mol%) and to
      be capable of encoding 152 non-overlapping open reading frames (ORFs). Three ORFs
      were unique to AgMNPV-2D, one of which (ag31) had similarity to eukaryotic
      poly(ADP-ribose) polymerases. The lack of chiA and v-cath may explain some of the
      success and growth of the AgMNPV biological control programme, as it may explain
      the high recovery of polyhedra sequestered inside dead larvae in the field, which
      are collected and used for further application as biological pesticides in
      soybean fields. The genome organization was similar to that of the Choristoneura
      fumiferana defective MNPV (CfDefNPV). Most of the variation between the two
      genomes took place near highly repetitive regions, which were also closely
      associated with bro-coding regions. The separation of the NPVs into groups I and
      II was supported by: (i) a phenogram of the complete genomes of 28 baculovirus
      and Heliothis zea virus 1, (ii) the most parsimonious reconstruction of gene
      content along the phenograms and (iii) comparisons of genomic features. Moreover,
      these data also reinforced the notion that group I of the NPVs can be split
      further into the AgMNPV lineage (AgMNPV, CfDefNPV, Epiphyas postvittana NPV,
      Orgyia pseudotsugata MNPV and C. fumiferana MNPV), sharing eight defining genes,
      and the Autographa californica MNPV (AcMNPV) lineage (AcMNPV, Rachiplusia ou NPV
      and Bombyx mori NPV), sharing nine defining genes.

PMID- 17030858
TI  - Cap-dependent and hepatitis C virus internal ribosome entry site-mediated
      translation are modulated by phosphorylation of eIF2alpha under oxidative stress.
AB  - Chronic hepatitis C is often associated with oxidative stress. Hepatitis C virus
      (HCV) utilizes an internal ribosome entry site (IRES) element for translation, in
      contrast to cap-dependent translation of the majority of cellular proteins. To
      understand how virus translation is modulated under oxidative stress, HCV IRES
      mediated translation was compared with cap-dependent translation using a
      bicistronic reporter construct and hydrogen peroxide (H2O2) as a stress inducer.
      In H2O2-sensitive HeLa cells, H2O2 repressed translation in a time- and dose
      dependent manner, concomitant with the kinetics of eIF2alpha phosphorylation. A
      phosphomimetic of eIF2alpha, which mimics the structure of the phosphorylated
      eIF2alpha, was sufficient to repress translation in the absence of H2O2. In H2O2
      resistant HepG2 cells, H2O2 activated both HCV IRES-mediated and cap-dependent
      translation, associated with an increased level of phospho-eIF2alpha. It was
      postulated that H2O2 might stimulate translation in HepG2 cells via an eIF2alpha
      independent mechanism, whereas the simultaneous phosphorylation of eIF2alpha
      repressed part of the translational activities. Indeed, the translational
      repression was released in the presence of a non-phosphorylatable mutant,
      eIF2alpha-SA, resulting in further enhancement of both translational activities
      after exposure to H2O2. In HuH7 cells, which exhibited an intermediate level of
      sensitivity towards H2O2, both HCV IRES-mediated and cap-dependent translational
      activities were upregulated after treatment with various doses of H2O2, but the
      highest level of induction was achieved with a low level of H2O2, which may
      represent the physiological level of H2O2. At this level, the HCV IRES-mediated
      translation was preferentially upregulated compared with cap-dependent
      translation.

PMID- 17030859
TI  - Dual topology of the processed hepatitis C virus protein NS4B is influenced by
      the NS5A protein.
AB  - Among the least-known hepatitis C virus proteins is the non-structural protein 4B
      (NS4B). It localizes to the endoplasmic reticulum (ER) membrane and induces
      membrane changes, resulting in a membranous web that is reported to be the locale
      for virus replication. A model was presented previously for the topology of
      recombinant HCV NS4B of the 1a genotype based on in vitro data. In this model,
      the N-terminal tail of a considerable fraction of the NS4B molecules was
      translocated into the ER lumen via a post-translational process, giving the
      protein a dual transmembrane topology. It is now reported that translocation of
      the N terminus also occurs for processed NS4B expressed in cells in the context
      of the polyprotein. In the presence of NS5A, however, a lower degree of
      translocation was observed, which may indicate that NS5A influences the topology
      of NS4B. In vitro expression studies of NS4B from all major genotypes
      demonstrated that translocation of the N terminus to the ER lumen is conserved
      across genotypes. This clearly suggests an important function for this feature.
      Furthermore, when disrupting a previously reported amphipathic helix (AH) in the
      N terminus of NS4B, translocation was inhibited. As a disrupted AH also abolished
      the ability of NS4B to rearrange membranes, these data indicate for the first
      time an association between translocation of the N terminus and membrane
      rearrangement. Finally, the present experiments also confirm the predicted
      location of the first luminal loop to be around aa 112.

PMID- 17030860
TI  - Ngoye virus: a novel evolutionary lineage within the genus Flavivirus.
AB  - By using degenerate primers deduced from conserved patterns in the flavivirus
      polymerase gene, a novel RNA virus was discovered in Rhipicephalus ticks sampled
      from members of the family Bovidae in Senegal. It was named Ngoye virus (NGOV)
      after the location from which it was isolated. Viral particles could be observed
      by electron microscopy, but isolation in vertebrate or invertebrate cell lines or
      by intracerebral infection of newborn mice remained unsuccessful. This is
      atypical of recognized arboviruses. The characterization of 4176 nt of the non
      structural genes revealed that NGOV is a novel flavivirus species. It forms a
      distinct phylogenetic lineage related distantly to previously identified members
      of the genus Flavivirus. Analysis of genetic data suggested that the processing
      of the NGOV polyprotein and the organization of its replication complex are
      similar to those of flaviviruses. Together with other recent data, these findings
      suggest that a large number of viruses related distantly to 'classical' arthropod
      borne flaviviruses remain to be discovered.

PMID- 17030861
TI  - Mutagenesis analysis of the NS2B determinants of the Alkhurma virus NS2B-NS3
      protease activation.
AB  - Alkhurma virus (ALKV) is a tick-borne class 4 flavivirus responsible for several
      human cases of haemorrhagic fever in Saudi Arabia, with no specific treatment
      currently available. The viral RNA encodes a serine protease (NS2B-NS3),
      essential for virus replication in infected cells, that constitutes an attractive
      target for antiviral compounds. In an attempt to identify residues and motifs on
      NS2B that are necessary for protease activity of the ALKV NS2B-NS3 complex, a
      series of modified NS2B-NS3 proteins was constructed, with point mutations on
      particular residues or with the NS2B domain derived from two different viruses.
      Four mutants and the two chimeric proteins exhibited reduction of protease
      activity against BAPNA (a p-nitroanilide substrate). The results demonstrate that
      tight complementarity of the protein sequences is necessary for NS2B-dependent
      activation of NS3. The results also determine residues in the ALKV NS2B cofactor
      essential for protease activation, giving new insights into protease function in
      flaviviruses.

PMID- 17030862
TI  - Identification of Japanese encephalitis virus-inducible genes in mouse brain and
      characterization of GARG39/IFIT2 as a microtubule-associated protein.
AB  - Several mouse central nervous system genes have been identified that are
      differentially regulated during Japanese encephalitis virus (JEV) infection,
      including those which have not been reported to be induced by any other
      neurotropic virus. Interestingly, approximately 80 % of JEV-inducible genes
      identified in this study are also induced by Sindbis virus, indicating activation
      of common host signalling pathways by these two viruses, despite their diverse
      life cycles. One of these, the glucocorticoid attenuated response gene 39
      (GARG39, also known as IFIT2, ISG54 and MuP54) was characterized further. It was
      demonstrated that GARG39 protein interacts with microtubules in vitro, co
      localizes with beta-tubulin in vivo and is enriched in the mitotic spindle of non
      neuronal cells undergoing mitosis. While GARG39 was known for a long time as an
      inflammation-inducible glucocorticoid attenuated protein, its identification as a
      microtubule-associated protein in this study suggests a possible role for this
      protein in cell proliferation, virion assembly/transport and microtubule
      dynamics.

PMID- 17030863
TI  - Secondary structure of dengue virus type 4 3' untranslated region: impact of
      deletion and substitution mutations.
AB  - Several studies have generated computer-based predictions of secondary structure
      of the 3' untranslated region (UTR) of Dengue virus (DEN); however, experimental
      verification of the formation of these structures in vitro is lacking. This study
      assessed the congruence of Mfold predictions of secondary structure of the core
      region of the DEN type 4 3' UTR with nuclease maps of this region. Maps and
      predictions were largely consistent. Maps supported the existence of previously
      predicted pseudoknots and identified putative regions of dynamic folding.
      Additionally, this study investigated previously identified conserved elements in
      the flavivirus 3' UTR that differ among viruses with different modes of
      transmission. Specific regions of mosquito-borne DEN type 4 were either deleted
      or replaced with homologous sequences from tick-borne Langat virus. All of these
      mutations caused substantial distortion of secondary structure, yet viruses
      carrying these mutations were viable.

PMID- 17030864
TI  - Direct repeats in the 3' untranslated regions of mosquito-borne flaviviruses:
      possible implications for virus transmission.
AB  - Direct repeats (DRs) of 20-45 nucleotide conserved sequences (CS) and repeated CS
      (RCS), separated by non-conserved sequences up to 100 nucleotides long, were
      previously described in the 3' untranslated region (3'UTR) of the three major
      mosquito-borne flavivirus (MBFV) subgroups, represented by Japanese encephalitis
      virus, Yellow fever virus and Dengue virus. Each subgroup exhibits a specific
      pattern of DRs, the biological significance of which has not yet been adequately
      addressed. The DRs were originally identified using conventional alignment
      programs based on the assumption that genetic variation is driven primarily by
      nucleotide substitutions. Since there are no recognized alignment programs that
      can adequately accommodate very divergent sequences, a method has been devised to
      construct and analyse a substantially improved 3'UTR alignment between these
      highly divergent viruses, based on the concept that deletions and/or insertions,
      in addition to substitutions, are important drivers of 3'UTR evolution. This
      'robust alignment' approach demonstrated more extensive homologies in the 3'UTR
      than had been recognized previously and revealed the presence of similar DRs,
      either intact or as sequence 'remnants', in all the MBFV subgroups. The relevance
      of these observations is discussed in relation to (i) the function of DRs as
      elements of replication enhancement, (ii) the evolution of RNA secondary
      structures and (iii) the significance of DRs and secondary structures in MBFV
      transmissibility between vertebrate and invertebrate hosts.

PMID- 17030865
TI  - Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close
      to the genus Parechovirus in the family Picornaviridae.
AB  - Duck hepatitis virus type 1 (DHV-1) was previously classified as an enterovirus,
      based primarily on observed morphology and physicochemical properties of the
      virion. The complete nucleotide sequences of two strains (DRL-62 and R85952) of
      DHV-1 have been determined. Excluding the poly(A) tail, the genomes are 7691 and
      7690 nt, respectively, and contain a single, large open reading frame encoding a
      polyprotein of 2249 aa. The genome of DHV-1 is organized as are those of members
      of the family Picornaviridae: 5' untranslated region (UTR)-VP0-VP3-VP1-2A1-2A2-2B
      2C-3A-3B-3C-3D-3' UTR. Analysis of the genomic and predicted polyprotein
      sequences revealed several unusual features, including the absence of a predicted
      maturation cleavage of VP0, the presence of two unrelated 2A protein motifs and a
      3' UTR extended markedly compared with that of any other picornavirus. The 2A1
      protein motif is related to the 2A protein type of the genus Aphthovirus and the
      adjacent 2A2 protein is related to the 2A protein type present in the genus
      Parechovirus. Phylogenetic analysis using the 3D protein sequence shows that the
      two DHV-1 strains are related more closely to members of the genus Parechovirus
      than to other picornaviruses. However, the two DHV-1 strains form a monophyletic
      group, clearly distinct from members of the genus Parechovirus.

PMID- 17030866
TI  - Quantitative analysis of poliomyelitis-like paralysis in mice induced by a
      poliovirus replicon.
AB  - Poliovirus (PV) infection causes severe paralysis, typically of the legs, by
      destruction of the motor neurons in the spinal cord. In this study, the
      relationship between PV replication in the spinal cord, damage in the motor
      neurons and poliomyelitis-like paralysis was analysed in transgenic mice
      expressing the human PV receptor (TgPVR21). First, a PV replicon encoding firefly
      luciferase in place of the capsid genes (PV-Fluc mc) was trans-encapsidated in
      293T cells and the trans-encapsidated PV-Fluc mc (TE-PV-Fluc mc) was then
      inoculated into the spinal cords of TgPVR21 mice. TE-PV-Fluc mc was recovered
      with a titre of 6.3 x 10(7) infectious units ml(-1), which was comparable to
      those of PV1 strains. TgPVR21 mice inoculated with TE-PV-Fluc mc showed non
      lethal paralysis of the hindlimbs, with severity ranging from a decline in grip
      strength to complete flaccid paralysis. The replication of TE-PV-Fluc mc in the
      spinal cord reached peak levels at 10 h post-inoculation (p.i.), followed by the
      appearance of paralysis at as early as 12 h p.i., reaching a plateau at 16 h p.i.
      Histological analysis showed a correlation between the lesion and the severity of
      the clinical symptoms in most mice. However, severe paralysis could also be
      observed with an apparently low lesion score, where as few as 5.3 x 10(2) motor
      neurons (1.4 % of the susceptible cells in the lumbar cord) were infected by TE
      PV-Fluc mc. These results indicate that PV replication in a small population of
      the motor neurons was critical for severe residual poliomyelitis-like paralysis
      in TgPVR21 mice.

PMID- 17030868
TI  - Feline calicivirus replication: requirement for polypyrimidine tract-binding
      protein is temperature-dependent.
AB  - The interaction of host-cell nucleic acid-binding proteins with the genomes of
      positive-stranded RNA viruses is known to play a role in the translation and
      replication of many viruses. To date, however, the characterization of similar
      interactions with the genomes of members of the family Caliciviridae has been
      limited to in vitro binding analysis. In this study, Feline calicivirus (FCV) has
      been used as a model system to identify and characterize the role of host-cell
      factors that interact with the viral RNA. It was demonstrated that polypyrimidine
      tract-binding protein (PTB) interacts specifically with the 5' sequences of the
      FCV genomic and subgenomic RNAs. Using RNA interference it was shown that PTB is
      required for efficient FCV replication in a temperature-dependent manner. siRNA
      mediated knockdown of PTB resulted in a 15- to 100-fold reduction in virus titre,
      as well as a concomitant reduction in viral RNA and protein synthesis at 32
      degrees C. In addition, virus-induced cytopathic effect was significantly delayed
      as a result of an siRNA-mediated reduction in PTB levels. A role for PTB in the
      calicivirus life cycle was more apparent at temperatures above and below 37
      degrees C, fitting with the hypothesis that PTB functions as an RNA chaperone,
      potentially aiding the folding of RNA into functional structures. This is the
      first functional demonstration of a host-cell protein interacting with a
      calicivirus RNA.

PMID- 17030867
TI  - Identification of the cleavage sites of sapovirus open reading frame 1
      polyprotein.
AB  - Sapovirus (SaV), a member of the family Caliciviridae, is a causative agent of
      acute gastroenteritis in humans and swine and is currently divided into five
      genogroups, GI-GV. The proteolytic processing of the SaV open reading frame 1
      (ORF1) polyprotein with a human GII SaV Mc10 strain has recently been determined
      and the products are arranged in the following order: NH(2)-p11-p28-p35 (NTPase)
      p32-p14 (VPg)-p70 (Pro-Pol)-p60 (VP1)-COOH. The cleavage site between p14 (VPg)
      and p70 (Pro-Pol) was identified as E(1055)/A(1056) by N-terminal amino acid
      sequencing. To identify other cleavage sites, a series of GII SaV Mc10 full
      length clones containing disrupted potential cleavage sites in the ORF1
      polyprotein were constructed and used to generate linear DNA templates for in
      vitro coupled transcription-translation. The translation products were analysed
      by SDS-PAGE or by immunoprecipitation with region-specific antibodies. N-terminal
      amino acid sequencing with Escherichia coli-expressed recombinant proteins was
      also used to identify the cleavage site between p32 and p14. These approaches
      enabled identification of the six cleavage sites of the Mc10 ORF1 polyprotein as
      E(69)/G(70), Q(325)/G(326), Q(666)/G(667), E(940)/A(941), E(1055)/A(1056) and
      E(1722)/G(1723). The alignment of the SaV full-length ORF1 amino acid sequences
      indicated that the dipeptides used for the cleavage sites were either E or Q at
      the P1 position and A, G or S at the P1' position, which were conserved in the
      GI, GII, GIII, GIV and GV SaV ORF1 polyprotein.

PMID- 17030869
TI  - Inter- and intra-variant genetic heterogeneity of human coronavirus OC43 strains
      in France.
AB  - Human coronavirus OC43 (HCoV-OC43) causes acute, self-limited respiratory
      infections. A close relationship between bovine coronaviruses (BCoVs) and HCoV
      OC43 has recently been demonstrated. This study includes seven clinical, non-cell
      culture-adapted, contemporary HCoV-OC43 strains detected in France in 2003. By
      using RT-PCR and clonal sequencing of the S1 gene of HCoV-OC43, the inter-variant
      heterogeneity of the HCoV-OC43 circulating strains was studied and the intra
      variant diversity was assessed by investigation of a quasispecies cloud. This
      paper brings to the forefront a high genetic diversity of circulating HCoV-OC43
      variants. Genetically different groups are defined among the variants described
      in this study. One of these variants holds characteristics of an outlier and
      presents a deletion of 12 nt, also found in BCoV strains. Moreover, the presence
      of HCoV-OC43 as a quasispecies cloud in vivo during an acute respiratory-tract
      illness was discovered. It has also been revealed that quasispecies-cloud sizes
      are similar for the two viral populations tested.

PMID- 17030870
TI  - Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and
      genetic variation analysis.
AB  - Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL
      CoV) or SARS coronavirus-like virus. These viruses, together with SARS
      coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive
      cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively
      named group 2b (G2b). In this study, complete genome sequences of two additional
      group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus
      ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b
      CoV isolates have an identical genome organization and share an overall genome
      sequence identity of 88-92 % among themselves and between them and the
      human/civet isolates. The most variable regions are located in the genes encoding
      nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are
      compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists
      in the bat habitat and has evolved from a common ancestor of SARS-CoV.

PMID- 17030871
TI  - Enhanced antiviral antibody secretion and attenuated immunopathology during
      influenza virus infection in nitric oxide synthase-2-deficient mice.
AB  - NOS2 gene-deficient (NOS2(-/-)) mice are less susceptible than wild-type
      (NOS2(+/+)) mice to infection with Influenza A virus. Virus titres in the lungs
      of influenza-infected NOS2(-/-) mice are significantly lower than those in
      NOS2(+/+) mice, with enhanced viral clearance in NOS2(-/-) mice dependent on
      gamma interferon (IFN-gamma). The current study was undertaken to ascertain the
      role of specific components of the immune response in promoting virus clearance
      in influenza-infected NOS2(-/-) mice. Levels of T cell- and natural killer cell
      mediated cytotoxicity in the lungs of virus-infected mice were not significantly
      different between NOS2(+/+) and NOS2(-/-) mice. However, virus-infected NOS2(-/-)
      mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more
      viable B cells and plasmablasts, along with greater levels of IFN-gamma, were
      found in NOS2(-/-) splenocyte cultures stimulated with B-cell mitogens. In
      addition to the early reduction in virus titres, clinical symptoms and
      proinflammatory cytokine production were attenuated in NOS2(-/-) mice. Thus,
      NOS2(-/-) B cells are capable of responding rapidly to influenza virus infection
      by proliferating and preferentially producing antibody of the IgG2a subtype. The
      relationship between viral load and the development of immunopathology is
      discussed.

PMID- 17030872
TI  - Role of the influenza virus heterotrimeric RNA polymerase complex in the
      initiation of replication.
AB  - Both transcription and replication of the influenza virus RNA genome are
      catalysed by a virus-specific RNA polymerase. Recently, an in vitro assay, based
      on the synthesis of pppApG, for the initiation of replication by recombinant RNA
      polymerase in the absence of added primer was described. Here, these findings are
      extended to show that adenosine, AMP and ADP can each substitute for ATP in
      reactions catalysed by either recombinant ribonucleoprotein or RNA polymerase
      complexes with either model virion RNA (vRNA) or cRNA promoters. The use of
      either adenosine or AMP, rather than ATP, provides a convenient, sensitive and
      easy assay of replication initiation. Moreover, no pppApG was detected when a PB1
      PA dimer, rather than the trimeric polymerase, was used to catalyse synthesis,
      contrasting with a previous report using baculovirus-expressed influenza RNA
      polymerase. Overall, it is suggested that the heterotrimeric polymerase is
      essential for the initiation of replication.

PMID- 17030873
TI  - Matrix protein of Vesicular stomatitis virus harbours a cryptic mitochondrial
      targeting motif.
AB  - Vesicular stomatitis virus (VSV) is a rhabdovirus that has attracted attention of
      late as an oncolytic virus and as a vaccine vector. Mutations in the matrix (M)
      gene of VSV yield attenuated strains that may be very useful in both settings. As
      a result of this interest in the M protein, this study analysed various M-green
      fluorescent protein (GFP) fusion constructs. Remarkably, fusion of the N terminus
      of the M protein to GFP targeted the fluorescent protein to the surface of
      mitochondria. Mutational analysis indicated that a mitochondrial-targeting motif
      exists within aa 33-67. Expression of these fusion proteins led to loss of
      mitochondrial membrane permeability and to an alteration in mitochondrial
      organization mirroring that seen during viral infection. In addition, a portion
      of the M protein present in infected cells co-purified with mitochondria. This
      work may indicate a novel function for this multifunctional viral protein.

PMID- 17030874
TI  - Identification of a cytotoxic T-lymphocyte (CTL) epitope recognized by Gag
      specific CTLs in cynomolgus monkeys infected with simian/human immunodeficiency
      virus.
AB  - Infection of Macaca fascicularis (cynomolgus monkey) with chimeric simian/human
      immunodeficiency virus (SHIV) provides a valuable experimental animal model of
      AIDS and is widely used for the development of human immunodeficiency virus
      vaccine strategies. In these settings, analysis of CD8(+) T-cell responses during
      infection represents one of the key parameters for monitoring the evaluation of
      containment of virus replication. The generation of Gag-specific CD8(+) T cells
      was reported previously from a cynomolgus monkey infected with SHIV89.6P by
      taking advantage of a B-lymphoblastoid cell line transduced with a retroviral
      vector expressing simian immunodeficiency virus (SIV) Gag. Here, it was shown
      that these cytotoxic T lymphocytes (CTLs) demonstrated specificity for a single 9
      aa peptide (NCVGDHQAA) spanning aa 192-200 of the SIVmac239 p55(gag) protein.
      Furthermore, a positive response was found against the same epitope in one of six
      other SHIV-infected monkeys. This newly identified SIV Gag CTL epitope in SHIV
      infected cynomolgus monkeys will be a useful tool for monitoring and evaluating
      Gag-specific immune responses during vaccination and infection in the cynomolgus
      monkey model of AIDS.

PMID- 17030875
TI  - Identification of an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope in
      rotavirus VP6 protein.
AB  - The function of cytotoxic T lymphocytes (CTLs) in rotavirus (RV) infection in
      humans is poorly understood. To date, no RV-specific human leukocyte antigen
      (HLA) class I-restricted T-cell epitopes have been described. In this study, four
      peptides derived from human RV Wa strain VP6 protein were predicted by computer
      algorithms and verified by an HLA*0201-binding assay. Two peptides with high
      affinity for HLA-A*0201 molecules were further assessed. The CTLs induced in
      vitro by P340-348 (TLLANVTAV)-loaded autologous dendritic cells from peripheral
      blood lymphocytes of HLA-A*0201-matched healthy donors released gamma interferon
      specifically upon stimulation with P340-348-loaded T2 cells. The CTLs lysed both
      P340-348-loaded T2 cells and human RV Wa strain-infected HLA-A*0201(+) Caco-2
      cells in an antigen-specific and HLA-A*0201-restricted manner. At the same time,
      P340-348 was shown to be immunogenic in vivo in HLA-A*0201/Kb transgenic mice. It
      is proposed that P340-348 is an HLA-A*0201-restricted CTL epitope.

PMID- 17030876
TI  - The 5' non-translated region of Varroa destructor virus 1 (genus Iflavirus):
      structure prediction and IRES activity in Lymantria dispar cells.
AB  - Structure prediction of the 5' non-translated region (NTR) of four iflavirus RNAs
      revealed two types of potential internal ribosome entry site (IRES), which are
      discriminated by size and level of complexity, in this group of viruses. In
      contrast to the intergenic IRES of dicistroviruses, the potential 5' IRES
      structures of iflaviruses do not have pseudoknots. To test the activity of one of
      these, a bicistronic construct was made in which the 5' NTR of Varroa destructor
      virus 1 (VDV-1) containing a putative IRES was cloned in between two reporter
      genes, enhanced green fluorescent protein and firefly luciferase (Fluc). The
      presence of the 5' NTR of VDV-1 greatly enhanced the expression levels of the
      second reporter gene (Fluc) in Lymantria dispar Ld652Y cells. The 5' NTR was
      active in a host-specific manner, as it showed lower activity in Spodoptera
      frugiperda Sf21 cells and no activity in Drosophila melanogaster S2 cells.

PMID- 17030877
TI  - An iterated sequence in the genome of Banana bunchy top virus is essential for
      efficient replication.
AB  - Banana bunchy top virus (BBTV) has a multi-component genome of circular, single
      stranded DNA. BBTV replicates via a rolling-circle mechanism, probably involving
      sequence-specific interaction of the replication initiation protein (Rep) with
      iterated sequences (iterons) within the viral genome. Three putative iterons
      (designated F1, F2 and R), with the sequence GGGAC, have been identified in the
      intergenic region of each BBTV component. To investigate their role in
      replication, each of the iterons was mutated, singularly and in tandem, in a BBTV
      DNA-N 1.1mer and the ability of these molecules to be replicated by the BBTV
      'master' Rep was evaluated in banana cells using transient biolistic assays. All
      iteron mutants were replicated less efficiently than the native DNA-N. Mutation
      of the F1 and R iterons caused a 42 and 62 % reduction in DNA-N replication,
      respectively, whereas mutation of the F2 and combined F1F2 iteron virtually
      abolished DNA-N replication.

PMID- 17030878
TI  - Production of plum pox virus HC-Pro functionally active for aphid transmission in
      a transient-expression system.
AB  - Potyviruses are non-persistently transmitted by aphid vectors with the assistance
      of a viral accessory factor known as helper component (HC-Pro), a multifunctional
      protein that is also involved in many other essential processes during the virus
      infection cycle. A transient Agrobacterium-mediated expression system was used to
      produce Plum pox virus (PPV) HC-Pro in Nicotiana benthamiana leaves from
      constructs that incorporated the 5' region of the genome, yielding high levels of
      HC-Pro in agroinfiltrated leaves. The expressed PPV HC-Pro was able to assist
      aphid transmission of purified virus particles in a sequential feeding assay, and
      to complement transmission-defective variants of the virus. Also, HC-Pro of a
      second potyvirus, Tobacco etch virus (TEV), was expressed and found to be
      functional for aphid transmission. These results show that this transient system
      can be useful for production of functionally active HC-Pro in potyviruses, and
      the possible uses of this approach to study the mechanism of transmission are
      discussed.

PMID- 17030879
TI  - Arabidopsis tonoplast proteins TIP1 and TIP2 interact with the cucumber mosaic
      virus 1a replication protein.
AB  - The cucumber mosaic virus (CMV) replication complex has previously been shown to
      associate with cellular membranes. However, it remains unknown whether any host
      factors participate in this process. In this study, five groups of Arabidopsis
      tonoplast intrinsic protein (TIP) genes were isolated and the proteins they
      encoded were evaluated with regard to their interactions with CMV proteins. TIP1
      and TIP2 were found to interact with the CMV 1a protein in the Sos recruitment
      system, whereas no interactions with the other three TIP subgroups were observed
      in this assay. The interaction of CMV 1a with the TIP1 and TIP2 proteins was
      confirmed via co-immunoprecipitation assays. Additionally, CMV 1a co-localized
      with TIP1 and TIP2 in transfected Arabidopsis protoplasts. The findings of this
      study suggest that members of two TIP subfamilies might affect CMV replication
      via interaction with CMV 1a in the tonoplasts.

PMID- 17030880
TI  - Phylogeography of Ustilago maydis virus H1 in the USA and Mexico.
AB  - Ustilago maydis virus H1 (Umv-H1) is a mycovirus that infects Ustilago maydis, a
      fungal pathogen of maize. As Zea mays was domesticated, it carried with it many
      associated symbionts, such that the subsequent range expansion and cultivation of
      maize should have affected maize symbionts' evolutionary history dramatically.
      Because transmission of Umv-H1 takes place only through cytoplasmic fusion during
      mating of U. maydis individuals, the population dynamics of U. maydis and maize
      are expected to affect the population structure of the viral symbiont strongly.
      Here, the impact of changes in the evolutionary history of U. maydis on that of
      Umv-H1 was investigated. The high mutation rate of this virus allows inferences
      to be made about the evolution and divergence of Umv-H1 lineages as a result of
      the recent changes in U. maydis geographical and genetic structure. The
      phylogeographical history and genetic structure of Umv-H1 populations in the USA
      and Mexico were determined by using analyses of viral nucleotide sequence
      variation. Infection and recombination frequencies, genetic diversity and rates
      of neutral evolution were also assessed, to make inferences regarding
      evolutionary processes underlying the population genetic structure of ancestral
      and descendent populations. The results suggest that Mexico represents the
      ancestral population of Umv-H1, from which the virus has been carried with U.
      maydis populations into the USA. Thus, the population dynamics of one symbiont
      represent a major evolutionary force on the co-evolutionary dynamics of symbiotic
      partners.

PMID- 17030881
TI  - Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed
      deer (Odocoileus virginianus) infected with chronic wasting disease.
AB  - To investigate the possible presence of disease-associated prion protein (PrP(d))
      in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of
      diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer
      (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus
      elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western
      immunoblot and immunohistochemistry (IHC). PrP(d) was detected in samples of
      heart muscle from seven of 16 CWD-infected white-tailed deer, including one free
      ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer
      samples, nor in the single CWD-infected moose. For white-tailed deer, PrP(d) was
      detected by Western blot at multiple sites throughout the heart; IHC results on
      ventricular sections of both elk and white-tailed deer showed positive staining
      in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of
      PrP(d) in cardiac tissues were estimated from Western blot band intensity to be
      lower than levels found in brain tissue. PrP(d) was not detected in diaphragm,
      triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of
      the study subjects. This is the first report of PrP(d) in cardiac tissue from
      transmissible spongiform encephalopathy-infected ruminants in the human food
      chain and the first demonstration by immunological assays of PrP(d) in any
      striated muscle of CWD-infected cervids.

PMID- 17030882
TI  - Patterns of PrPCWD accumulation during the course of chronic wasting disease
      infection in orally inoculated mule deer (Odocoileus hemionus).
AB  - Patterns of abnormal prion protein (PrP) accumulation during the course of
      chronic wasting disease (CWD) infection were studied and the distribution and
      timing of disease-associated PrP (PrP(CWD)) deposition and lesions in 19 mule
      deer (Odocoileus hemionus) 90-785 days after oral inoculation were described.
      PrP(CWD) deposition occurred relatively rapidly and widely in lymphoid tissues,
      later in central and peripheral nervous tissues and sporadically in a variety of
      tissues and organs in terminal disease stages. Development of spongiform
      encephalopathy lagged behind PrP(CWD) deposition in the central nervous system
      (CNS), but occurred in the same neuroanatomical locations. PrP(CWD) deposition in
      the lymphatic and nervous systems tended to be consistent and progressive in
      specific organs and tissues. Locations of PrP(CWD) deposition were similar
      between deer of two PrP genotypes (225SS and 225SF), but the time course differed
      between genotypes: in 225SF deer, PrP(CWD) accumulated more slowly in lymphatic
      tissues than in 225SS animals, but that disparity was small in comparison to the
      disparity between genotypes in timing of deposition in CNS tissue. These data
      confirm retropharyngeal lymph node and medulla oblongata at the level of the obex
      as early sites of PrP(CWD) accumulation in mule deer with CWD. Data on the
      relative time frames for and genetic influences on PrP(CWD) accumulation may also
      offer insights about epidemic dynamics and potential control strategies.

PMID- 17030883
TI  - Lymphoid follicles of the ileal Peyer's patch of lambs express low levels of PrP,
      as demonstrated by quantitative real-time RT-PCR on microdissected tissue
      compartments, in situ hybridization and immunohistochemistry.
AB  - The expression level of normal cellular prion protein (PrP(C)) is thought to
      influence the transmission of transmissible spongiform encephalopathies (TSEs)
      from the peripheral entry site to the site of pathological changes in the central
      nervous system. In many TSEs, the clinical disease is preceded by a period in
      which the agent accumulates in lymphoid organs, particularly in association with
      follicular dendritic cells of lymphoid follicles. As the probable route of entry
      of the TSE agent is via the gut, the expression profile of PrP was examined in
      well-developed gut-associated lymphoid tissue of lambs, the ileal Peyer's patch,
      by laser microdissection and real-time RT-PCR. Lymphoid follicles were found to
      have very low levels of expression, whilst highest levels were detected in the
      outer submucosa and the muscular layer. These findings were supported by in situ
      hybridization and immunohistochemistry, which showed specific labelling in nerve
      cells in ganglia of the submucosal (Meissner's) and myenteric (Auerbach's) plexi
      of the enteric nervous system. Based on the assumption that potential sites for
      conversion to the scrapie-related prion protein (PrP(Sc)) should display high
      levels of expression of PrP(C), this study suggests that the accumulation of
      PrP(Sc) in the lymphoid follicles of the Peyer's patch is not preceded by PrP
      conversion in the same tissue compartment.

PMID- 17030884
TI  - Congruence and functions of personal and cultural values: do my values reflect my
      culture's values?
AB  - Two studies are described examining the correlation between self- and culture
      referenced values at a culture level (Study 1) and correlation between self- and
      culture-referenced values and self-reported behavior at an individual level
      (Study 2). It is found that values related to individual-group relationships
      (embeddedness) and expression and experience of affective feelings and emotions
      (affective autonomy) are significantly correlated at a culture level. In Study 2,
      culture-referenced values are shown to correlate with behaviors attached to
      social norms, whereas self-rated values are found to correlate with behaviors
      that are not norm-governed. Implications for measurement of cultural values and
      cultural and cross-cultural research designs are discussed.

PMID- 17030885
TI  - Why are attributions to discrimination interpersonally costly? A test of system-
      and group-justifying motivations.
AB  - In two studies, Whites' endorsement of system-justifying beliefs predicted
      increased negativity toward Blacks who blamed negative events on discrimination.
      Whites' system-justifying beliefs were not associated with negativity toward
      Blacks who blamed negative events on other internal causes, external causes, or
      nondiscriminatory unfairness. These negative reactions toward discrimination
      claimants were mediated by perceptions that the claimant held dissimilar values
      and failed to take personal responsibility for outcomes. In both studies,
      participants' White Identification did not moderate the relationship between the
      Black target's attribution for failure and subsequent negative perceptions of
      that individual, thus providing evidence against a group-justification
      explanation of these findings.

PMID- 17030886
TI  - A novel approach to assessing achievement goals in the context of the 2 x 2
      framework: identifying distinct profiles of individuals with different dominant
      achievement goals.
AB  - In two studies, individuals' dominant achievement goals were assessed using a
      new, simple, and conceptually precise measure based on Elliot and McGregor's
      (2001) 2 x 2 framework. Next, the four groups were compared in terms of
      achievement-relevant variables, including need for achievement, perfectionism,
      perceived competence, interest, and graded performance. As expected, a very high
      percentage (approximately 85%) of people indicated they had a dominant
      achievement goal. Furthermore, the results suggest that individuals with
      different dominant achievement goals have clear, distinct profiles that can be
      characterized as positively valenced (mastery-approach), both positively and
      negatively valenced (performance-approach), negatively valenced (performance
      avoidance), or neither positively nor negatively valenced (mastery-avoidance).

PMID- 17030887
TI  - What you want (and do not want) affects what you see (and do not see): avoidance
      social goals and social events.
AB  - Two studies examined the influence of approach and avoidance social goals on
      memory for and evaluation of ambiguous social information. Study 1 found that
      individual differences in avoidance social goals were associated with greater
      memory of negative information, negatively biased interpretation of ambiguous
      social cues, and a more pessimistic evaluation of social actors. Study 2
      experimentally manipulated social goals and found that individuals high in
      avoidance social motivation remembered more negative information and expressed
      more dislike for a stranger in the avoidance condition than in the approach
      condition. Results suggest that avoidance social goals are associated with
      emphasizing potential threats when making sense of the social environment.

PMID- 17030888
TI  - The effects of a parenting prime on sex differences in mate selection criteria.
AB  - This study tested an evolutionary hypothesis that the mere prospect of caring for
      a child will increase sex differences in human mate selection criteria. That is,
      women would adopt a stronger preference for socially dominant men when parenting
      had been primed and men would adopt a stronger preference for physically
      attractive women when parenting had been primed. Male and female university
      students were randomly assigned to be exposed to a parenting prime or a
      nonparenting prime. Following the priming procedure, participants rated the
      romantic appeal of a target person of the opposite sex. Exposure to the parenting
      prime, the target's social dominance, and the target's physical attractiveness
      were orthogonally manipulated. As predicted, women adopted a stronger mate
      preference for social dominance when parenting was at the forefront of the mind.
      Contrary to predictions, the parenting prime had no effect on men's mate
      preference for physical attractiveness.

PMID- 17030889
TI  - Conformism moderates the relations between values, anticipated regret, and
      behavior.
AB  - The purpose of the present study was to evaluate the moderating effect of
      Conformism values on the relations between other values and behavior. The authors
      expected people low, but not high, in Conformism to behave in a manner that is
      consistent with their personal values related to self-transcendence versus self
      enhancement. In Study 1 (N = 199), such values predicted actual altruistic
      behavior, as estimated by other-reports, but only if Conformism values were low.
      In Study 2 (N = 189), only people who considered Conformism values to be
      relatively unimportant showed expected connections between self-transcendence
      values and anticipated regret in hypothetical scenarios having negative
      consequences. The data are interpreted as supporting the view that (a)
      anticipated regret motivates value-consistent behavior, (b) self-transcendence
      values in particular are connected to altruistic behavior and to anticipated
      regret, but (c) conformity to social norms moderates these connections.

PMID- 17030890
TI  - The effect of age and role information on expectations for big five personality
      traits.
AB  - In four studies, the authors investigated the extent to which expectations for
      personality traits in age-graded roles correspond to patterns of personality
      trait change across the life course. In Studies 1 (N = 43) and 2 (N = 126), the
      authors examined the age-graded roles of high school student, college student,
      parent, and grandparent and found that expectations for how people behave in
      these age-graded roles showed strong parallels to the documented pattern of
      personality trait development and that this pattern of expectations was largely
      shared by younger and older participants. In Studies 3 (N = 252) and 4 (N = 123),
      the authors separated age and role information (e.g., marital, parental, and
      employment status) and found that people use both sources of information
      independently in forming expectations of others. The implications for
      understanding the interplay of expectations and personality trait development are
      discussed.

PMID- 17030891
TI  - Voicing conflict: preferred conflict strategies among incremental and entity
      theorists.
AB  - The way individuals choose to handle their feelings during interpersonal
      conflicts has important consequences for relationship outcomes. In this article,
      the authors predict and find evidence that people's implicit theory of
      personality is an important predictor of conflict behavior following a
      relationship transgression. Incremental theorists, who believe personality can
      change and improve, were likely to voice their displeasure with others openly and
      constructively during conflicts. Entity theorists, who believe personality is
      fundamentally fixed, were less likely to voice their dissatisfactions directly.
      These patterns were observed in both a retrospective study of conflict in dating
      relationships (Study 1) and a prospective study of daily conflict experiences
      (Study 2). Study 2 revealed that the divergence between incremental and entity
      theorists was increasingly pronounced as conflicts increased in severity: the
      higher the stakes the stronger the effect.

PMID- 17030892
TI  - Childhood physical and emotional abuse by a parent: transference effects in adult
      interpersonal relations.
AB  - Extending research on transference and the relational self (Andersen & Chen,
      2002), female undergraduates with or without a history of physical and emotional
      abuse by a loved parent participated in an experiment manipulating parental
      resemblance and threat-relevant interpersonal context in a new person.
      Transference elicited differences not evident in the control condition between
      abused and nonabused participants' responses, with greater rejection expectancy,
      mistrust, dislike, and emotional indifference reported by abused participants.
      Immediate implicit affect was more positive in transference than in the control
      condition regardless of abuse history. Yet, abused participants in transference
      also reported increased dysphoria that was markedly attenuated when interpersonal
      threat was primed, and no such pattern occurred among nonabused participants.
      Evidence that interpersonally guarded and affectively complex responses are
      triggered in transference among previously abused individuals suggests that this
      social-cognitive process may underlie long-term interpersonal difficulties
      associated with parental abuse.

PMID- 17030893
TI  - The role of perceived similarity in supportive responses to victims of negative
      life events.
AB  - The authors examined whether participants' perceived similarity to an ostensible
      victim of a negative life event influenced their supportiveness during a live
      interaction. Two competing models were considered: (a) increased similarity would
      be associated with increased supportiveness through attraction to the target and
      (b) increased similarity would be associated with decreased supportiveness
      through anxiety (due to heightened vulnerability). Participants (N = 241) met
      individually with a confederate posing as a cancer patient. Reactions were
      assessed, including verbal and nonverbal behaviors, both before and after the
      interaction, by participants themselves and by observers of the interaction.
      Results supported a model based on the classic similarity/attraction paradigm:
      Perceived similarity indirectly predicted participant-reported
      supportiveness/warmth and smiling through its relationship to attraction. Results
      extend the literature on similarity and attraction to the stress and coping arena
      and suggest that emphasizing perceived similarities to victims would be
      beneficial.

PMID- 17030894
TI  - Bolstering implementation plans for the long haul: the benefits of simultaneously
      boosting self-concordance or self-efficacy.
AB  - Recent studies suggest that implementation planning exercises may not be as
      helpful for long-term, self-initiated goals as for short-term, assigned goals.
      Two studies used the personal goal paradigm to explore the impact of
      implementation plans on goal progress over time. Study 1 examined whether
      administering implementation plans in an autonomy supportive manner would
      facilitate goal progress relative to a neutral, control condition and a condition
      in which implementation plans were administered in a controlling manner. Study 2
      examined whether combining implementation plans with a self-efficacy boosting
      exercise would facilitate goal progress relative to a neutral, control condition
      and a typical implementation condition. The results showed that implementation
      plans alone did not result in greater goal progress than a neutral condition but
      that the combination of implementation plans with either autonomy support or self
      efficacy boosting resulted in significantly greater goal progress.

PMID- 17030895
TI  - Group morality and intergroup relations: cross-cultural and experimental
      evidence.
AB  - An observational, cross-cultural study and an experimental study assessed
      behaviors indicative of a moral code that condones, and even values, hostility
      toward outgroups. The cross-cultural study, which used data from the Standard
      Cross-Cultural Sample (Murdock & White, 1969), found that for preindustrial
      societies, as loyalty to the ingroup increased the tendency to value outgroup
      violence more than ingroup violence increased, as did the tendencies to engage in
      more external than internal warfare, and enjoy war. The experimental study found
      that relative to guilt-prone group members who were instructed to remain
      objective, guilt-prone group members who were instructed to be empathic with
      their ingroup were more competitive in an intergroup interaction. The findings
      from these studies suggest that group morality is associated with intergroup
      conflict.

PMID- 17030896
TI  - Taste receptors in the gastrointestinal tract. II. L-amino acid sensing by
      calcium-sensing receptors: implications for GI physiology.
AB  - The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for
      several key nutrients, notably Ca2+ ions and L-amino acids, and is expressed
      abundantly throughout the gastrointestinal tract. While its role as a Ca2+ ion
      sensor is well recognized, its physiological significance as an L-amino acid
      sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion
      is only now coming to light. This review focuses on the CaR's amino acid sensing
      properties at both the molecular and cellular levels and considers new and
      putative physiological roles for the CaR in the amino acid-dependent regulation
      of gut hormone secretion, epithelial transport, and satiety.

PMID- 17030897
TI  - Differentiation of the gastric mucosa. II. Role of gastrin in gastric epithelial
      cell proliferation and maturation.
AB  - Gastrin is the principal hormonal inducer of gastric acid secretion. The cellular
      targets for gastrin in the stomach are the acid-secreting parietal cell and
      histamine-producing enterochromaffin-like (ECL) cell. Gastrin is also a growth
      factor, with hypergastrinemia resulting in increased proliferation of gastric
      progenitor cells and a thickened mucosa. This review presents insights into
      gastrin function revealed by genetically engineered mouse models, demonstrating a
      new role for gastrin in the maturation of parietal and ECL cells. Thus, gastrin
      regulates many aspects of gastric physiology, with tight regulation of gastrin
      levels required to maintain balanced growth and function of gastric epithelial
      cells.

PMID- 17030898
TI  - IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via
      modulating Fas expression and altering caspase-8 and FLIP expression.
AB  - We have previously shown that the absence of Fas/Fas ligand significantly reduced
      tissue damage and intestinal epithelial cell (IEC) apoptosis in an in vivo model
      of T cell-mediated enteropathy. This enteropathy was more severe in IL-10
      deficient mice, and this was associated with increased serum levels of IFN-gamma
      and TNF-alpha and an increase in Fas expression on IECs. In this study, we
      investigated the potential of IL-10 to directly influence Fas expression and Fas
      induced IEC apoptosis. Mouse intestinal epithelial cell lines MODE-K and IEC4.1
      were cultured with IFN-gamma, TNF-alpha, or anti-Fas monoclonal antibody (mAb) in
      the presence or absence of IL-10. Fas expression and apoptosis were determined by
      FACScan analysis of phycoerythrin-anti-Fas mAb staining and annexin V staining,
      respectively. Treatment with a combination of IFN-gamma and TNF-alpha induced
      significant apoptosis. Anti-Fas mAb alone did not induce much apoptosis unless
      cells were pretreated with IFN-gamma and TNF-alpha. These IECs constitutively
      expressed low levels of Fas, which significantly increased by preincubation of
      the cells with IFN-gamma and TNF-alpha. Treatment with cytokine or cytokine plus
      anti-Fas mAb increased apoptosis, which correlated with a decreased Fas
      associated death domain IL-1-converting enzyme-like inhibitory protein (FLIP)
      level, increased caspase-8 activity, and subsequently increased caspase-3
      activity. IL-10 diminished both cytokine- and anti-Fas mAb-induced apoptosis, and
      this was correlated with decreased cytokine-induced Fas expression, increased
      FLIP, and decreased caspase-8 and caspase-3 activity. In conclusion, IL-10
      modulated cytokine induction of Fas expression on IEC cell lines and regulated
      IEC susceptibility to TNF-alpha, IFN-gamma, and Fas-mediated apoptosis. These
      findings suggest that IL-10 directly modulates IEC responses to T cell-mediated
      apoptotic signals.

PMID- 17030899
TI  - Interaction of complement and leukocytes in severe acute pancreatitis: potential
      for therapeutic intervention.
AB  - In acute pancreatitis, local as well as systemic organ complications are mediated
      by the activation of various inflammatory cascades. The role of complement in
      this setting is unclear. The aim of the present study was to determine the level
      of complement activation in experimental pancreatitis, to evaluate the
      interaction of complement and leukocyte-endothelium activation, and to assess the
      effects of complement inhibition by soluble complement receptor 1 (sCR1) in this
      setting. Necrotizing pancreatitis was induced in Wistar rats by the combination
      of intravenous cerulein and retrograde infusion of glycodeoxycholic acid into the
      biliopancreatic duct; edematous pancreatitis was induced by intravenous cerulein
      only. In control animals, a sham operation (midline laparotomy) was performed.
      Complement activation, leukocyte sequestration, and pancreatic as well as
      pulmonary injury were assessed in the presence/absence of sCR1. Increased levels
      of C3a were found in necrotizing but not in edematous pancreatitis. When
      complement activation in necrotizing pancreatitis was blocked by sCR1, levels of
      C3a and total hemolytic activity (CH50) were decreased. Leukocyte-endothelial
      interaction, as assessed by intravital microscopy, and pancreatic as well as
      pulmonary organ injury (wet-to-dry weight ratio, MPO activity, and histology)
      were ameliorated by sCR1. As a result of the present study, necrotizing but not
      edematous pancreatitis is characterized by significant and early complement
      activation. Based on the interaction of complement and leukocytes, complement
      inhibition by sCR1 may be a valuable option in the treatment of leukocyte
      associated organ injury in severe pancreatitis.

PMID- 17030900
TI  - Platelet-activating factor in the enteric nervous system of the guinea pig small
      intestine.
AB  - Platelet-activating factor (PAF) is a proinflammatory mediator that may influence
      neuronal activity in the enteric nervous system (ENS). Electrophysiology,
      immunofluorescence, Western blot analysis, and RT-PCR were used to study the
      action of PAF and the expression of PAF receptor (PAFR) in the ENS. PAFR
      immunoreactivity (IR) was expressed by 6.9% of the neurons in the myenteric
      plexus and 14.5% of the neurons in the submucosal plexus in all segments of the
      guinea pig intestinal tract as determined by double staining with anti-human
      neuronal protein antibody. PAFR IR was found in 6.1% of the neurons with IR for
      calbindin, 35.8% of the neurons with IR for neuropeptide Y (NPY), 30.6% of the
      neurons with IR for choline acetyltransferase (ChAT), and 1.96% of the neurons
      with IR for vasoactive intestinal peptide (VIP) in the submucosal plexus. PAFR IR
      was also found in 1.5% of the neurons with IR for calbindin, 51.1% of the neurons
      with IR for NPY, and 32.9% of the neurons with IR for ChAT in the myenteric
      plexus. In the submucosal plexus, exposure to PAF (200-600 nM) evoked
      depolarizing responses (8.2 +/- 3.8 mV) in 12.4% of the neurons with S-type
      electrophysiological behavior and uniaxonal morphology and in 12.5% of the
      neurons with AH-type electrophysiological behavior and Dogiel II morphology,
      whereas in the myenteric preparations, depolarizing responses were elicited by a
      similar concentration of PAF in 9.5% of the neurons with S-type
      electrophysiological behavior and uniaxonal morphology and in 12.0% of the
      neurons with AH-type electrophysiological behavior and Dogiel II morphology. The
      results suggest that subgroups of secreto- and musculomotor neurons in the
      submucosal and myenteric plexuses express PAFR. Coexpression of PAFR IR with ChAT
      IR in the myenteric plexus and ChAT IR and VIP IR in the submucosal plexus
      suggests that PAF, after release in the inflamed bowel, might act to elevate the
      excitability of submucosal secretomotor and myenteric musculomotor neurons.
      Enhanced excitability of motor neurons might lead to a state of neurogenic
      secretory diarrhea.

PMID- 17030901
TI  - Phospholipase D and extracellular signal-regulated kinase in hepatic stellate
      cells: effects of platelet-derived growth factor and extracellular nucleotides.
AB  - We have previously provided evidence suggesting that phosphatidic acid, possibly
      derived from the hydrolysis of phosphatidylcholine by phospholipase D (PLD), is
      involved in platelet-derived growth factor (PDGF)-mediated increases in
      extracellular signal-regulated kinase (ERK) activity and DNA synthesis in rat
      hepatic stellate cells (HSC), the primary fibrogenic cells of the liver. A recent
      study has shown the presence of P2Y nucleotide receptors on HSC that are coupled
      to contraction and synthesis of the matrix component, alpha1-procollagen, leading
      to the suggestion that they may represent a new therapeutic target in the
      treatment of liver fibrosis. However, although extracellular nucleotides have
      been shown to stimulate both PLD and ERK, and to elicit proliferation of
      fibrogenic cells outside the liver, their effect on these parameters in HSC have
      not yet been investigated. PLD activity was determined by [3H]choline release and
      [3H]phosphatidylbutanol production, ERK activity by Western blotting, and DNA
      synthesis by [3H]thymidine incorporation. We report here, for the first time in
      HSC, that extracellular nucleotides stimulate PLD activity and a sustained
      activation of ERK. However, in contrast to PDGF, nucleotides had negligible
      effects on DNA synthesis. Moreover, the effects of PDGF and nucleotides on PLD
      and ERK were not additive, suggesting activation of the same PLD isoform and pool
      of ERK. The data demonstrate that nucleotide-stimulated PLD and ERK activities
      are not coupled to DNA synthesis in HSC. Instead, these responses may be linked
      to other phenotypic changes associated with activated HSC such as increases in
      contraction, motility, or extracellular matrix deposition.

PMID- 17030902
TI  - An age-structured model of dendritic cell trafficking in the lung.
AB  - As the sentinels of the immune system, dendritic cells (DC) play a critical role
      in initiating and maintaining appropriate T cell responses through capture and
      presentation of antigen, costimulation, and mediator release. Although much is
      known about certain aspects of DC function, the exact relationship between lung
      epithelial DC precursor populations in the blood and their functional role in
      antigen presentation are not clearly understood. I created an age-structured
      mathematical model for DC trafficking into the lung to address this question.
      While capturing experimentally observed system dynamics, I found that blood DC
      are preferentially recruited over blood monocytes. For short-lived antigens, the
      model results suggest that lung epithelial DC derived from blood DC exhibit a
      625% increase in antigen density compared with those derived from blood
      monocytes. Finally, these results motivate future experimental studies to clarify
      aspects of DC trafficking in the lung.

PMID- 17030903
TI  - BMP-dependent activation of caspase-9 and caspase-8 mediates apoptosis in
      pulmonary artery smooth muscle cells.
AB  - Germ line mutations in the bone morphogenetic protein (BMP) receptor type II
      (BMPRII) gene have been found in >50% of familial idiopathic pulmonary arterial
      hypertension (IPAH) patients and in 30% of sporadic cases of IPAH. Mutations of
      BMPRII occur in the extracellular ligand-binding domain, in the cytoplasmic
      serine/threonine kinase domain, or in the long carboxy terminus domain of unknown
      function. In this study, we demonstrate that BMPs promote apoptotic cell death in
      normal human pulmonary artery smooth muscle cells (PASMCs) by activation of
      caspases-3, -8, and -9, cytochrome c release, and downregulation of Bcl-2. Normal
      PASMCs expressing a kinase domain mutant or a carboxy-terminal domain deletion
      mutant of BMPRII identified in IPAH patients are resistant to BMP-mediated
      apoptosis. This dominant-negative effect may act in heterozygous patients and
      lead to the development of the pulmonary vascular medial hypertrophy found in
      IPAH patients. Our study also demonstrates an essential role of the carboxy
      terminus domain of BMPRII in the activation of the apoptotic signaling cascade.

PMID- 17030904
TI  - Treatment of plague: promising alternatives to antibiotics.
AB  - Plague still poses a significant threat to human health, and interest has been
      renewed recently in the possible use of Yersinia pestis as a biological weapon by
      terrorists. The septicaemic and pneumonic forms are always lethal if untreated.
      Attempts to treat this deadly disease date back to the era of global pandemics,
      when various methods were explored. The successful isolation of the plague
      pathogen led to the beginning of more scientific approaches to the treatment and
      cure of plague. This subsequently led to specific antibiotic prophylaxis and
      therapy for Y. pestis. The use of antibiotics such as tetracycline and
      streptomycin for the treatment of plague has been embraced by the World Health
      Organization Expert Committee on Plague as the 'gold standard' treatment.
      However, concerns regarding the development of antibiotic-resistant Y. pestis
      strains have led to the exploration of alternatives to antibiotics. Several
      investigators have looked into the use of alternatives, such as immunotherapy,
      non-pathogen-specific immunomodulatory therapy, phage therapy, bacteriocin
      therapy, and treatment with inhibitors of virulence factors. The alternative
      therapies reported in this review should be further investigated by comprehensive
      studies of their clinical application for the treatment of plague.

PMID- 17030905
TI  - Mutation of luxS affects motility and infectivity of Helicobacter pylori in
      gastric mucosa of a Mongolian gerbil model.
AB  - Helicobacter pylori is associated with gastric disorders in humans and some
      experimental animals, and possesses the luxS/type 2 autoinducer (AI-2) system.
      The effects of a specific luxS mutation on the characteristics of H. pylori were
      examined. On 0.3 % agar medium, motility of H. pylori HPKY08 (luxS : : cat) was
      significantly lower than that of wild-type H. pylori TK1402. The luxS
      complemented strain HPKY21 exhibited motility comparable to that of H. pylori
      TK1402. It was shown that the luxS/AI-2 system plays an important role in H.
      pylori motility. The luxS mutant exhibited a reduced infection rate relative to
      the wild-type parent strain TK1402 in a Mongolian gerbil model. At 3 months after
      oral inoculation, lower numbers of H. pylori were detected by semi-quantitative
      real-time reverse transcription PCR (qRT-PCR) in luxS(-) mutant-infected gerbils
      than in TK1402-infected gerbils. Gastric inflammation and increased antibody
      titre for H. pylori were observed in TK1402-infected gerbils only.

PMID- 17030906
TI  - Cytolethal distending toxins in Shiga toxin-producing Escherichia coli: alleles,
      serotype distribution and biological effects.
AB  - To assess the prevalence of cytolethal distending toxin (CDT) among Shiga toxin
      producing Escherichia coli (STEC), 202 STEC strains were investigated using PCRs
      targeting various cdt alleles (cdt-I to cdt-V). Seven of the 202 strains
      contained cdt-III and an additional seven contained cdt-V. All 14 cdt-positive
      strains produced biologically active CDT, as demonstrated by a progressive
      distension of cultured Chinese hamster ovary cells. The CDT-positive STEC
      belonged to eight different serotypes, including sorbitol-fermenting O157 : NM
      (non-motile). The data demonstrate that CDT is present in some STEC serotypes
      only. However, more studies are required to evaluate whether CDT presence is
      associated with severe disease.

PMID- 17030907
TI  - Detection of enteroaggregative Escherichia coli in faecal samples from patients
      in the community with diarrhoea.
AB  - The aim of this study was to assess the usefulness of a multiplex PCR assay
      targeting the aat, aaiA and astA genes for the detection of typical and atypical
      enteroaggregative Escherichia coli (EAEC) in bacterial cultures from faecal
      samples from patients with community-acquired diarrhoea. The isolates harbouring
      these genes were also tested using the HEp-2 cell-adhesion assay to clarify their
      EAEC status. aat, aai or astA was found in E. coli faecal isolates from 39 (7.8
      %) of 500 patients, and 20 of these strains adhered to HEp-2 cells in a pattern
      characteristic of EAEC. Eight isolates carrying the aai or astA gene but not the
      aat gene were shown to be HEp-2 cell test positive, although 12 strains with this
      genotype were HEp-2 cell test negative. Using the HEp-2 adhesion assay as the
      gold standard, the addition of primers detecting aaiA and astA to the aat PCR
      increased the number of EAEC isolates detected, but identified strains of E. coli
      that were not EAEC. The variety of genotypes exhibiting aggregative adherence
      highlights the problems associated with developing a molecular diagnostic test
      for EAEC. This PCR assay detects a variety of strains exhibiting characteristics
      of the EAEC group, making it a useful tool for identifying both typical and
      atypical EAEC.

PMID- 17030908
TI  - Antigenicity of borrelial protein BBK32 fragments in early Lyme borreliosis.
AB  - Recombinantly produced borrelial BBK32 protein fragments originating from
      Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii were
      evaluated as antigens in the serology of Lyme borreliosis (LB). In ELISA, a mid
      portion hydrophilic fragment reacted with LB patient sera. Of the 23 patients
      with culture- or PCR-positive erythema migrans (EM), 43 % at diagnosis and 52 %
      at convalescence were positive for at least one Borrelia species-specific variant
      BBK32 fragment antigen. In parallel ELISAs with BBK32 whole proteins from the
      three borrelial subspecies as antigens, 17 % at diagnosis and 26 % at
      convalescence were positive. These results suggest that BBK32 protein fragments
      may improve the early IgG serology of LB compared to the BBK32 whole protein.

PMID- 17030909
TI  - Rapid molecular identification of fungal pathogens in corneal samples from
      suspected keratomycosis cases.
AB  - An increase in the incidence of fungal infections has highlighted the need for
      rapid and precise detection and identification methods in clinical mycology. This
      report describes the data obtained on corneal samples from 24 patients with
      suspected keratomycosis using a conventional cultural approach in parallel with
      PCR amplification and sequencing of the internal transcribed spacers (ITSs) of
      the rDNA regions. Using the cultural approach, seven samples (58.3 % of the 12
      samples positive for an infectious pathogen) tested positive for a fungal
      aetiology, with final identification taking a mean time of more than 5 days. In
      two cases, diagnosis required 10 days. Using the ITS-based molecular approach, a
      direct diagnosis was obtained in only five of the seven fungus-positive cases
      (71.4 %) starting from the clinical samples, but identification was still
      possible in all seven cases within 24 h (by using 16 h cultures for the two
      remaining cases). Despite the less-than-optimal sensitivity when working directly
      on clinical samples, the obtained data indicate that the molecular strategy used
      in this study is a useful complement to the conventional diagnostic approaches
      used for keratomycosis and, in particular, allows precise and fast fungal
      identification, in response to the clinical requirements. Similar studies on
      larger panels of patients and on different clinical samples are required for
      further investigation of the clinical potential of ITS-based approaches in the
      diagnosis of mycotic infections.

PMID- 17030910
TI  - Rapid antibiotic sensitivity testing and trimethoprim-mediated filamentation of
      clinical isolates of the Enterobacteriaceae assayed on a novel porous culture
      support.
AB  - A porous inorganic material (Anopore) was employed as a microbial culture and
      microcolony imaging support. Rapid Anopore-based antibiotic sensitivity testing
      (AST) methods were developed to assess the growth of clinical isolates, with the
      primary focus on testing the response of the Enterobacteriaceae to trimethoprim,
      but with the method supporting a wider applicability in terms of strains and
      antibiotics. It was possible to detect the growth of Enterobacter aerogenes after
      25 min culture and to distinguish a trimethoprim-sensitive from a trimethoprim
      resistant strain with 40 min incubation. MIC(90) determinations were made on
      Anopore; these were in good agreement with the results from the Vitek 2 and E
      test methods. The Anopore method correctly identified sensitive (40/40) and
      resistant (17/17) strains of the Enterobacteriaceae and other Gram-negative rods
      within only 2-3 h culture. Additionally, a trimethoprim-resistant subpopulation
      (10 % of population) could be detected by microcolony formation within 2 h, and a
      smaller subpopulation (1 %) after 3.5 h. These results suggest that this is a
      viable approach for the rapid AST of purified strains, and that it may be able to
      deal with mixed populations. The microscopic examination of microcolonies during
      AST is an advantage of this method which revealed additional information.
      Filamentation triggered by trimethoprim was discovered in many species of the
      Enterobacteriaceae for which this phenomenon has not previously been reported.
      Filamentation was characterized by heterogeneity in terms of cell length, and
      also uneven nucleic acid distribution and flattening of damaged cells. The
      development and application of Anopore-based AST within clinical diagnostics is
      discussed.

PMID- 17030911
TI  - Insertion sequence ISEcp1-like element connected with a novel aph(2'') allele
      [aph(2'')-Ie] conferring high-level gentamicin resistance and a novel
      streptomycin adenylyltransferase gene in Enterococcus.
AB  - Enterococcus casseliflavus HZ95 is an enterococcus with high-level resistance to
      aminoglycosides. Nine genes responsible for high-level aminoglycoside resistance,
      including aac(6')-Ie-aph(2'')-Ia, aph(2'')-Ib, aph(2'')-Ic, aph(2'')-Id, aph(3')
      IIIa, aac(6')-Ii, ant(3')-Ia, ant(4')-Ia and ant(6')-Ia, were not detected in
      HZ95. An 8 kb fragment from unconjugative plasmids of HZ95 was cloned, and
      expressed gentamicin resistance in Escherichia coli DH5alpha. The genetic
      structures ( approximately 8 kb DNA fragment) containing these aminoglycoside
      modifying enzyme genes in Ent. casseliflavus HZ95 were determined. The deduced
      amino acid sequence of the novel aph(2'') allele, aph(2'')-Ie, had 93.7 % amino
      acid identity with APH(2'')-Id. The aph(2'')-Ie gene was bracketed upstream by an
      insertion sequence (IS)Ecp1-like element and downstream by a streptomycin
      adenylyltransferase gene (str). The streptomycin adenylyltransferase encoded by
      the str gene had 80.3 % amino acid identity with the protein encoded by aadE. The
      plasmid of approximately 16 kb could hybridize with a PCR-generated aph(2'')-Ie
      intragenic probe. The ISEcp1-like element had 91 % identity with ISEcp1. ISEcp1,
      which commonly acts as a key factor in the dissemination of CTX-M-type beta
      lactamase genes in Gram-negative bacteria, has not been reported in Enterococcus.

PMID- 17030912
TI  - Molecular characterization of isoniazid-resistant clinical isolates of
      Mycobacterium tuberculosis from the USA.
AB  - Drug-resistant tuberculosis poses a significant problem for treatment. The
      mechanisms of resistance to the front-line drug isoniazid (INH) are complex and
      can be mediated by katG, inhA and other unknown genes. To identify the percentage
      of INH-resistant strains with no katG or inhA mutation, this study characterized
      a panel of 28 clinical isolates of Mycobacterium tuberculosis and five mutants
      derived from H37Rv resistant to INH. Seventeen of 33 resistant strains (51 %) had
      katG mutations with 12 of the 17 strains having the most common KatG Ser315Thr
      mutation. Three of the 17 strains with the KatG 315 mutation had an additional
      mutation in the inhA promoter and were resistant to a high level of INH.
      Seventeen of the 33 INH-resistant strains (51 %) had inhA mutations. The most
      common inhA promoter mutation was -15C-->T and was present in 13 of the 17 inhA
      mutations. This promoter mutation occurred alone without katG mutations and was
      associated with a low level of INH and ethionamide resistance. However, other
      inhA mutations were associated with katG mutations. No mutations were found in
      the ndh gene. Three of 33 strains (9 %) had no mutations in katG, inhA or ndh,
      indicating that their resistance was due to a new mechanism of resistance.
      Detection of the KatG Ser315Thr mutation and the -15C-->T inhA mutation accounted
      for 76 % (25/33) of the INH-resistant strains and should be useful for rapid
      detection of INH-resistant strains by molecular tests.

PMID- 17030913
TI  - High level of ciprofloxacin resistance and its molecular background among
      Campylobacter jejuni strains isolated in the United Arab Emirates.
AB  - The antibiotic sensitivity and the serotype and molecular type (MT) distribution
      of 41 Campylobacter jejuni strains isolated from individual patients in Tawam
      Hospital, Al Ain, United Arab Emirates, were investigated. While all strains were
      sensitive to erythromycin (MIC 0.5-4 mg l(-1)), 35 isolates (85.4 %) exhibited
      resistance to ciprofloxacin (MIC 8-64 mg l(-1)). All resistant strains carried
      the Thr-86 to Ile mutation in the gyrase A (gyrA) gene, as shown by mismatch
      amplification mutation assay (MAMA) and confirmed by sequencing. Based on the
      partial sequences of gyrA, resistant isolates carried 10 distinct alleles, eight
      of them representing new variants. Strains were assigned to 30 MTs based on the
      combined results of PFGE and flaA PCR-RFLP typing. Eight of the 35 ciprofloxacin
      resistant strains, isolated over a period of more than 1 year, represented the
      largest MT, also carrying the same allelic variant of the gyrA gene. These
      results show that the local incidence of fluoroquinolone resistance among C.
      jejuni is one of the highest reported worldwide. It was also demonstrated that
      stable MTs could persist for a relatively long time among the clonally unrelated
      antibiotic-resistant isolates of C. jejuni. The data also emphasize the need to
      replace fluoroquinolones as empirical therapy for diarrhoea of undiagnosed
      aetiology.

PMID- 17030915
TI  - An improved multiple-locus variable number of tandem repeats analysis for
      Leptospira interrogans serovar Australis: a comparison with fluorescent amplified
      fragment length polymorphism analysis and its use to redefine the molecular
      epidemiology of this serovar in Queensland, Australia.
AB  - In this study, an improved multiple-locus variable number of tandem repeats
      analysis (MLVA) method based upon a previously published method is described.
      Improvements to the method included redesigned primers and PCR conditions,
      combined with pooled capillary electrophoresis using multicolored dyes. Allele
      sizes were converted into an allele string, and each unique allele string was
      assigned a numerical MLVA type (MVT). The improved MLVA method was then applied
      to 96 previously characterized Leptospira interrogans serovar Australis isolates
      from human and animal sources. The improved MLVA was found to have between six
      and 13 alleles at each locus, compared with three to eight in the original. The
      mean Hunter-Gaston diversity index (HGDI) for the improved MLVA method was 0.654,
      compared with 0.599 in the original; this increase in diversity was largely due
      to changes in the analysis of the variable number of tandem repeat (VNTR) data.
      When the improved MLVA method was compared with the fluorescent amplified
      fragment length polymorphism (FAFLP) method, there was a high level of
      concordance between the profiles; however, the MLVA method produced an additional
      four unique profiles amongst the subset of 30 isolates tested. Given that the
      improved MLVA method was found to be superior to the original MLVA method, it was
      subsequently used to redefine the molecular epidemiology of L. interrogans
      serovar Australis in Queensland, Australia. Using cluster analysis, the authors
      were able to demonstrate clonal links amongst rodent isolates, rodent and human
      isolates, and rodent and canine isolates. These results highlight the role of
      rodents in the disease, and also the potential role of MLVA in defining the
      molecular epidemiology of L. interrogans.

PMID- 17030914
TI  - Molecular typing and virulence markers of Yersinia enterocolitica strains from
      human, animal and food origins isolated between 1968 and 2000 in Brazil.
AB  - Molecular typing and virulence markers were used to evaluate the genetic profiles
      and virulence potential of 106 Yersinia enterocolitica strains. Of these strains,
      71 were bio-serotype 4/O : 3, isolated from human and animal clinical material,
      and 35 were of biotype 1A or 2 and of diverse serotypes, isolated from food in
      Brazil between 1968 and 2000. Drug resistance was also investigated. All the
      strains were resistant to three or more drugs. The isolates showed a virulence
      related phenotype in the aesculin, pyrazinamidase and salicin tests, except for
      the food isolates, only two of which were positive for these tests. For the other
      phenotypic virulence determinants (autoagglutination, Ca(++) dependence and Congo
      red absorption), the strains showed a diverse behaviour. The inv, ail and ystA
      genes were detected in all human and animal strains, while all the food isolates
      were positive for inv, and 3 % of them positive for ail and ystA. The presence of
      virF was variable in the three groups of strains. The strains were better
      discriminated by PFGE than by enterobacterial repetitive intergenic consensus PCR
      (ERIC-PCR). A higher genomic similarity was observed among the 4/O : 3 strains,
      isolated from human and animal isolates, than among the food strains, with the
      exception of two food strains possessing the virulence genes and grouped close to
      the 4/O : 3 strains by ERIC-PCR. Unusually, the results revealed the virulence
      potential of a bio-serotype 1A/O : 10 strain, suggesting that food contaminated
      with Y. enterocolitica biotype 1A may cause infection. This also suggests that
      ERIC-PCR may be used as a tool to reveal clues about the virulence potential of
      Y. enterocolitica strains. Furthermore, the results also support the hypothesis
      that animals may act as reservoirs of Y. enterocolitica for human infections in
      Brazil, an epidemiological aspect that has not been investigated in this country,
      confirming data from other parts of the world.

PMID- 17030916
TI  - Isolation of Vibrio cholerae O1 strains similar to pre-seventh pandemic El Tor
      strains during an outbreak of gastrointestinal disease in an island resort in
      Fiji.
AB  - Five strains of Vibrio cholerae O1, one each from an Australian and a New Zealand
      tourist with gastrointestinal illness returning from an island resort in Fiji and
      the remaining three from water sources located in the same resort, were
      extensively characterized. Conventional phenotypic traits that are used for
      biotyping of O1 V. cholerae categorized all five strains as belonging to the El
      Tor biotype. Genetic screening of 11 regions that are associated with virulence
      in V. cholerae showed variable results. The absence of genes comprising Vibrio
      seventh pandemic island-I (VSP-I) and VSP-II in all the strains indicated that
      these strains were very similar to the pre-seventh pandemic V. cholerae O1 El Tor
      strains. The ctxAB genes were absent in all strains whereas orfU and zot were
      present in four strains, indicating that the strains were non-toxigenic. Four
      strains carried a truncated CTX prophage. Although epidemiological and molecular
      studies suggested that these strains did not cause cholera amongst tourists at
      the resort, their similarity to pre-seventh pandemic strains, their prior
      association with gastrointestinal illness and their presence in the island resort
      setting warrant more attention.

PMID- 17030917
TI  - Genetic characteristics of Matlab variants of Vibrio cholerae O1 that are hybrids
      between classical and El Tor biotypes.
AB  - The Matlab variants of Vibrio cholerae O1, defined as hybrids between the
      classical and El Tor biotypes, were first isolated from hospitalized patients
      with acute secretory diarrhoea in Matlab, a rural area of Bangladesh. These
      variants could not be categorized as classical or El Tor biotypes by phenotypic
      and genotypic tests, and had representative traits of both the biotypes. A number
      of virulence-associated genes and/or gene clusters were screened by PCR and DNA
      sequencing. El Tor-specific gene clusters, Vibrio seventh-pandemic islands (VSP)
      I and -II and repeat toxin (RTX) were present in the genome of these variants,
      indicating their El Tor lineage, whereas the nucleotide-sequence-derived CtxB
      amino acid sequence of these strains grouped them under the classical biotype.
      Matlab variants possessed all the necessary genes to initiate pandemics. The
      genetic relatedness of Matlab variants to the V. cholerae strains recently
      isolated in Mozambique is another important observation of this study, which
      underscores the epidemiological significance of Matlab variants.

PMID- 17030918
TI  - An outbreak of psittacosis due to Chlamydophila psittaci genotype A in a
      veterinary teaching hospital.
AB  - An outbreak of psittacosis in a veterinary teaching hospital was recognized in
      December 2004. Outbreak management was instituted to evaluate the extent of the
      outbreak and to determine the avian source. Real-time PCR, serologic testing and
      sequencing of the ompA gene of Chlamydophila psittaci were performed. Sputum
      samples from patients, throat-swab samples from exposed students and staff, and
      faecal specimens from parrots and pigeons were tested. In this outbreak, 34 %
      (10/29) of the tested individuals were infected. The clinical features of the
      infection ranged from none to sepsis with multi-organ failure requiring intensive
      care-unit admission. C. psittaci genotype A was identified as the outbreak
      strain. Parrots, recently exposed to a group of cockatiels coming from outside
      the teaching facility, which were used in a practical class, appeared to be the
      source of the outbreak. One of the tested pigeons harboured an unrelated C.
      psittaci genotype B strain. The microbiological diagnosis by real-time PCR on
      clinical specimens allowed for rapid outbreak management; subsequent genotyping
      of the isolates identified the avian source. Recommendations are made to reduce
      the incidence and extent of future outbreaks.

PMID- 17030919
TI  - Arthroconidia production in Trichophyton rubrum and a new ex vivo model of
      onychomycosis.
AB  - The dermatophyte fungus Trichophyton rubrum often produces arthroconidia in vivo,
      and these cells are thought to be involved in pathogenesis, and, in shed skin
      scales, to act as a source of infection. The purpose of this study was (i) to
      examine the environmental and iatrogenic factors which affect arthroconidiation
      in T. rubrum in vitro, (ii) to look at arthroconidia formation in a large number
      of clinical isolates of T. rubrum and (iii) to develop a new model for the study
      of arthroconidia formation in nail tissue. Arthroconidia production was studied
      in T. rubrum grown on a number of media and under conditions of varying pH,
      temperature and CO(2) concentration. The effect of the presence of antifungals
      and steroids on arthroconidia formation was also examined. Nail powder from the
      healthy toenails of volunteers was used as a substrate for arthroconidial
      production. On Sabouraud dextrose agar in the presence of 10 % CO(2) plus air,
      arthroconidial formation occurred optimally at 37 degrees C and pH 7.5, and was
      maximal at 10 days. Most isolates of T. rubrum showed a similar level of
      arthroconidial production, and only two out of 50 strains were unable to produce
      arthroconidia. Subinhibitory levels of some antifungals and betamethasone
      resulted in the stimulation of arthroconidia formation. Arthroconidial production
      in ground nail material also occurred under the same optimal conditions, but took
      longer to reach maximal levels (14 days). These in vitro and ex vivo results
      provide a useful basis for the understanding of arthroconidium formation in vivo
      in infected tissues such as nails.

PMID- 17030920
TI  - Canine dermatophytosis caused by an anthropophilic species: molecular and
      phenotypical characterization of Trichophyton tonsurans.
AB  - Microsporum canis is the most common species isolated from canine and feline
      dermatophytosis in the world. However, this study reports a rare case of canine
      dermatophytosis caused by the anthropophilic dermatophyte Trichophyton tonsurans
      in the city of Fortaleza, Ceara, Brazil. The fungal characterization was
      performed by classical mycological examination and by genotypical analysis using
      the restriction enzymes Sau3A, RsaI, DdeI and EcoRI. The phenotypical
      characteristics were compatible with T. tonsurans. The results obtained in the
      genotypical analysis were similar to the digestion pattern of the ITS sequences
      for T. tonsurans strains. In addition, an antifungal susceptibility test was
      performed with griseofulvin, ketoconazole and itraconazole. The MICs were 0.5
      microg ml(-1) for griseofulvin, 0.25 microg ml(-1) for ketoconazole and 1 microg
      ml(-1) for itraconazole. This study emphasizes the adaptability of anthropophilic
      fungi such as T. tonsurans to animal conditions.

PMID- 17030921
TI  - Intractable colitis associated with chronic granulomatous disease.
AB  - The case of a 20-year-old Japanese man, diagnosed as having autosomal recessive
      chronic granulomatous disease (CGD), who was being treated with corticosteroids
      for intractable unclassified colitis, is described. He died from multiple organ
      failure following disseminated intravascular coagulation secondary to
      disseminated varicella-zoster virus (VZV) infection. He was diagnosed as an index
      case of CGD when 2 years old, was inoculated against VZV at the age of 5 years
      and had had an unremarkable course for 19 years. He was admitted to hospital
      because of a third episode of recurrent bloody diarrhoea. Clinical remission for
      each episode was achieved by intravenous corticosteroid therapy. Unclassified
      colitis associated with CGD was diagnosed based on a colonic biopsy demonstrating
      characteristic macrophages with lipofuscin deposits. From a treatment viewpoint,
      idiopathic inflammatory bowel disease (IBD) should be differentiated from
      secondary IBD occurring in CGD, in which immunosuppressive drugs including
      corticosteroids, still the mainstay of IBD treatment, should be avoided.

PMID- 17030922
TI  - Enterohepatic Helicobacter species isolated from the ileum, liver and colon of a
      baboon with pancreatic islet amyloidosis.
AB  - Microaerobic bacteria were isolated from a baboon with pancreatic islet
      amyloidosis and hepatitis. Phenotypic and molecular analyses identified two
      distinct helicobacters. Analyses of 16S rRNA demonstrated "Helicobacter macacae"
      in the ileum and liver, and Helicobacter cinaedi in the colon. To the best of the
      authors' knowledge, this is the first report describing the isolation of
      enterohepatic Helicobacter species from a baboon.

PMID- 17030923
TI  - Central nervous system borreliosis mimicking a pontine tumour.
AB  - In childhood, facial nerve palsy and headache are typical symptoms of second and
      third stage neuroborreliosis. While focal demyelination is occasionally observed
      on MRI scans, the appearance of a tumorous lesion is extremely rare. The case of
      a 10-year-old girl with neuroborreliosis mimicking a space-occupying lesion in
      the brainstem, without any previously recognized manifestations of borreliosis,
      is reported.

PMID- 17030924
TI  - Molecular evidence for vertical transmission of listeriosis, Taiwan.
AB  - The case is presented of a pregnant woman at the 31st week of gestation with
      Listeria monocytogenes bacteraemia and microabscess formation in the endometrium,
      who delivered an infant with disseminated infection (meningitis and bacteraemia).
      The two patients were successfully treated with intravenous ampicillin and
      gentamicin. Molecular typing using random amplified polymorphic DNA (RAPD)
      analysis disclosed that three isolates from the mother (blood) and infant (blood
      and cerebrospinal fluid) had identical RAPD profiles.

PMID- 17030925
TI  - Aeromonas agar is a useful selective medium for isolating aeromonads from faecal
      samples.

PMID- 17030926
TI  - A CTX-M extended-spectrum beta-lactamase in Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia.

PMID- 17030927
TI  - A CARB-like beta-lactamase gene from a multiple-drug-resistant Pseudomonas
      aeruginosa clinical isolate in China.

PMID- 17030928
TI  - Enterobacteria producing extended-spectrum beta-lactamases and IMP-1 metallo-beta
      lactamases isolated from Brazilian hospitals.

PMID- 17030929
TI  - International panel says CIHR needs management overhaul.

PMID- 17030930
TI  - Ibuprofen redux.

PMID- 17030931
TI  - Injection site gets 16-month extension.

PMID- 17030932
TI  - Schwarzenegger vetoes single-payer bill.

PMID- 17030933
TI  - Hepatitis E and cholera outbreak in Kathmandu.

PMID- 17030934
TI  - Quebec specialist taking government to court.

PMID- 17030935
TI  - Plan B available to women 18 and older in US.

PMID- 17030936
TI  - Uncontrollable movements in patient with diabetes mellitus.

PMID- 17030937
TI  - Patient sheet: tips for avoiding problems with polypharmacy.

PMID- 17030938
TI  - An infant with the "setting-sun" eye phenomenon.

PMID- 17030939
TI  - Accountability sought by patients following adverse events from medical care: the
      New Zealand experience.
AB  - BACKGROUND: Unlike Canada's medical malpractice system, patients in New Zealand
      who are dissatisfied with the quality of their care may choose between 2 well
      established medicolegal paths: one leads to monetary compensation and the other
      to nonmonetary forms of accountability. We compared the forms of accountability
      sought by patients and families in New Zealand who took different types of legal
      action following a medical injury. This study offers insights into the forms of
      accountability sought by injured patients and may help to inform tort-reform
      initiatives. METHODS: We reviewed compensation claims submitted to the Accident
      Compensation Corporation (ACC), New Zealand's national no-fault insurer,
      following injuries associated with admission to a public hospital in 1998 (n =
      582). We also reviewed complaint letters (n = 254) submitted to the national
      Health and Disability Commissioner (HDC) that same year to determine the forms of
      accountability sought by injured patients. We used univariable and multivariable
      analyses to compare sociodemographic and socioeconomic characteristics of
      patients who sought nonmonetary forms of accountability with those of patients
      who claimed compensation. RESULTS: Of 154 injured patients whose complaints were
      sufficiently detailed to allow coding, 50% sought corrective action to prevent
      similar harm to future patients (45% system change, 6% review of involved
      clinician's competence) and 40% wanted more satisfying communication (34%
      explanation, 10% apology). The odds that patients would seek compensation were
      significantly increased if they were in their prime working years (aged between
      30 and 64 years) (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.14-2.41)
      or had a permanent disability as a result of their injury (OR 1.75, 95% CI 1.14
      2.70). When injuries resulted in death, the odds of a compensation claim to the
      ACC were about one-eighth those of a complaint to the HDC (OR 0.13, 95% CI 0.08
      0.23). INTERPRETATION: Injured patients who pursue medicolegal action seek
      various forms of accountability. Compensation is important to some, especially
      when economic losses are substantial (e.g., with injury during prime working
      years or severe nonfatal injuries). However, others have purely nonmonetary
      goals, and ensuring alternative options for redress would be an efficient and
      effective response to their needs.

PMID- 17030940
TI  - Monetary and nonmonetary accountability following adverse medical events: options
      for Canadian patients.

PMID- 17030941
TI  - Is the Canadian health care system ready for donation after cardiac death? A note
      of caution.

PMID- 17030942
TI  - Clinical applications of cardiovascular magnetic resonance imaging.
AB  - Cardiovascular magnetic resonance imaging (MRI) has evolved from an effective
      research tool into a clinically proven, safe and comprehensive imaging modality.
      It provides anatomic and functional information in acquired and congenital heart
      disease and is the most precise technique for quantification of ventricular
      volumes, function and mass. Owing to its excellent interstudy reproducibility,
      cardiovascular MRI is the optimal method for assessment of changes in ventricular
      parameters after therapeutic intervention. Delayed contrast enhancement is an
      accurate and robust method used in the diagnosis of ischemic and nonischemic
      cardiomyopathies and less common diseases, such as cardiac sarcoidosis and
      myocarditis. First-pass magnetic contrast myocardial perfusion is becoming an
      alternative to radionuclide techniques for the detection of coronary
      atherosclerotic disease. In this review we outline the techniques used in
      cardiovascular MRI and discuss the most common clinical applications.

PMID- 17030943
TI  - Promotion of traditional lifestyles.

PMID- 17030944
TI  - Clinical utility of the Coombs test.

PMID- 17030945
TI  - Changing ethics: where to start?

PMID- 17030947
TI  - Integrin signaling is critical for pathological angiogenesis.
AB  - The process of postnatal angiogenesis plays a crucial role in pathogenesis of
      numerous diseases, including but not limited to tumor growth/metastasis, diabetic
      retinopathy, and in tissue remodeling upon injury. However, the molecular events
      underlying this complex process are not well understood and numerous issues
      remain controversial, including the regulatory function of integrin receptors. To
      analyze the role of integrin phosphorylation and signaling in angiogenesis, we
      generated knock-in mice that express a mutant beta3 integrin unable to undergo
      tyrosine phosphorylation. Two distinct models of pathological angiogenesis
      revealed that neovascularization is impaired in mutant beta3 knock-in mice. In an
      ex vivo angiogenesis assay, mutant beta3 knock-in endothelial cells did not form
      complete capillaries in response to vascular endothelial growth factor (VEGF)
      stimulation. At the cellular level, defective tyrosine phosphorylation in mutant
      beta3 knock-in cells resulted in impaired adhesion, spreading, and migration of
      endothelial cells. At the molecular level, VEGF stimulated complex formation
      between VEGF receptor-2 and beta3 integrin in wild-type but not in mutant beta3
      knock-in endothelial cells. Moreover, phosphorylation of VEGF receptor-2 was
      significantly reduced in cells expressing mutant beta3 compared to wild type,
      leading to impaired integrin activation in these cells. These findings provide
      novel mechanistic insights into the role of integrin-VEGF axis in pathological
      angiogenesis.

PMID- 17030948
TI  - IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent
      colitis.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
      gastrointestinal tract that is caused in part by a dysregulated immune response
      to the intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit is
      thought to be critical for the pathogenesis of IBD. We have analyzed the role of
      IL-12 versus IL-23 in two models of Helicobacter hepaticus-triggered T cell
      dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of
      infected T cell-sufficient hosts, and the other involving CD4+ T cell transfer
      into infected Rag-/- recipients. Our data demonstrate that IL-23 and not IL-12 is
      essential for the development of maximal intestinal disease. Although IL-23 has
      been implicated in the differentiation of IL-17-producing CD4+ T cells that alone
      are sufficient to induce autoimmune tissue reactivity, our results instead
      support a model in which IL-23 drives both interferon gamma and IL-17 responses
      that together synergize to trigger severe intestinal inflammation.

PMID- 17030949
TI  - Interleukin-23 drives innate and T cell-mediated intestinal inflammation.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the
      gastrointestinal tract involving aberrant activation of innate and adaptive
      immune responses. We have used two complementary models of IBD to examine the
      roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal
      inflammation. Our results clearly show that IL-23, but not IL-12, is essential
      for the induction of chronic intestinal inflammation mediated by innate or
      adaptive immune mechanisms. Depletion of IL-23 was associated with decreased
      proinflammatory responses in the intestine but had little impact on systemic T
      cell inflammatory responses. These results newly identify IL-23 as a driver of
      innate immune pathology in the intestine and suggest that selective targeting of
      IL-23 represents an attractive therapeutic approach in human IBD.

PMID- 17030950
TI  - High affinity germinal center B cells are actively selected into the plasma cell
      compartment.
AB  - A hallmark of T cell-dependent immune responses is the progressive increase in
      the ability of serum antibodies to bind antigen and provide immune protection.
      Affinity maturation of the antibody response is thought to be connected with the
      preferential survival of germinal centre (GC) B cells that have acquired
      increased affinity for antigen via somatic hypermutation of their immunoglobulin
      genes. However, the mechanisms that drive affinity maturation remain obscure
      because of the difficulty in tracking the affinity-based selection of GC B cells
      and their differentiation into plasma cells. We describe a powerful new model
      that allows these processes to be followed as they occur in vivo. In contrast to
      evidence from in vitro systems, responding GC B cells do not undergo plasma cell
      differentiation stochastically. Rather, only GC B cells that have acquired high
      affinity for the immunizing antigen form plasma cells. Affinity maturation is
      therefore driven by a tightly controlled mechanism that ensures only antibodies
      with the greatest possibility of neutralizing foreign antigen are produced.
      Because the body can sustain only limited numbers of plasma cells, this "quality
      control" over plasma cell differentiation is likely critical for establishing
      effective humoral immunity.

PMID- 17030952
TI  - Full of sound and fury, but signifying something: XVI International AIDS
      Conference, Toronto, Canada, August 13-18, 2006.
AB  - The biennial AIDS conference is often exhausting and irritating, but it offers a
      unique view of how science and society interact. It still deserves the support of
      basic scientists.

PMID- 17030951
TI  - Resolution of a chronic viral infection after interleukin-10 receptor blockade.
AB  - A defining characteristic of persistent viral infections is the loss and
      functional inactivation of antiviral effector T cells, which prevents viral
      clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by
      modulating the function of T cells and antigen-presenting cells. In this paper,
      we report that IL-10 production is drastically increased in mice persistently
      infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10
      receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of
      the persistent infection. IL-10 secretion was diminished and interferon gamma
      production by antiviral CD8+ T cells was enhanced. In persistently infected mice,
      CD8alpha+ dendritic cell (DC) numbers declined early after infection, whereas
      CD8alpha- DC numbers were not affected. CD8alpha- DCs supported IL-10 production
      and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R
      blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10
      priming by CD8alpha- DCs and enhancing antiviral responses and thereby resolving
      infection without causing immunopathology.

PMID- 17030953
TI  - Mass spectrometric detection of tissue proteins in plasma.
AB  - It has long been thought that blood plasma could serve as a window into the state
      of one's organs in health and disease because tissue-derived proteins represent a
      significant fraction of the plasma proteome. Although substantial technical
      progress has been made toward the goal of comprehensively analyzing the blood
      plasma proteome, the basic assumption that proteins derived from a variety of
      tissues could indeed be detectable in plasma using current proteomics
      technologies has not been rigorously tested. Here we provide evidence that such
      tissue-derived proteins are both present and detectable in plasma via direct mass
      spectrometric analysis of captured glycopeptides and thus provide a conceptual
      basis for plasma protein biomarker discovery and analysis.

PMID- 17030955
TI  - Thermoregulatory feeding in newborn infants: an update.

PMID- 17030954
TI  - EMB-4: a predicted ATPase that facilitates lin-12 activity in Caenorhabditis
      elegans.
AB  - The sel-6 gene was previously identified in a screen for suppressors of the egg
      laying defect associated with hypermorphic alleles of lin-12 (Tax et al. 1997).
      Here we show that sel-6 and two other previously defined genes, mal-2 and emb-4,
      are the same gene, now called "emb-4." We perform a genetic and molecular
      characterization of emb-4 and show that it functions cell autonomously as a
      positive regulator of lin-12 activity. Viable alleles identified as suppressors
      of lin-12 are partial loss-of-function mutations, whereas the null phenotype
      encompasses a range of lethal terminal phenotypes that apparently are not related
      to loss of lin-12/Notch signaling. emb-4 encodes a large nuclearly localized
      protein containing a predicted ATPase domain and has apparent orthologs in
      fission yeast, plants, and animals.

PMID- 17030956
TI  - Point: uncertainty in the economic analysis of school-based obesity prevention
      programs: urgent need for quality evaluation.

PMID- 17030957
TI  - Counterpoint: uncertainty in the economic analysis of school-based obesity
      prevention programs: urgent need for quality evaluation.

PMID- 17030958
TI  - Obesity in older adults: a systematic review of the evidence for diagnosis and
      treatment.
AB  - OBJECTIVE: Although obesity is increasing in older U.S. adults, treatment is
      controversial in this age group. We sought to examine evidence concerning
      obesity's health-related risks, diagnostic methods, and treatment outcomes in
      older individuals. RESEARCH METHODS AND PROCEDURES: We searched MEDLINE and
      Cochrane Library databases, consulted with experts, and examined bibliographies
      for English language studies discussing obesity in older adults (mean age > or =
      60), published between January 1980 and November 2005. Inclusion criteria were
      met by 32 longitudinal analyses, seven diagnostic studies, and 17 randomized
      controlled trial articles. At least two authors independently reviewed and
      abstracted study design, population, results, and quality information. RESULTS:
      Correlations between body fat and three anthropometric measures (BMI, waist
      circumference, waist-to-hip ratio) decrease with age but remain clinically
      significant. Obesity contributes to risk for several cardiovascular endpoints,
      some cancers, and impaired mobility but protects against hip fracture. The
      association between obesity and mortality declines as age increases. Intensive
      counseling strategies incorporating behavioral, dietary, and exercise components
      promote a weight loss of 3 to 4 kg over 1 to 3.3 years. The loss is linked with
      improved glucose tolerance, improved physical functioning, reduced incidence of
      diabetes and a combined hypertension and cardiovascular endpoint, and reduced
      bone density. DISCUSSION: In older adults, obesity can be diagnosed with standard
      clinical measures. Intensive counseling can promote modest sustained weight loss,
      but data are insufficient to evaluate surgical or pharmacological options.
      Obesity treatment is most likely to benefit individuals with high cardiovascular
      risk. Limited data suggest possible functional improvement. Treatment should
      incorporate measures to avoid bone loss.

PMID- 17030959
TI  - The promoter region of the adiponectin gene is a determinant in modulating
      insulin sensitivity in childhood obesity.
AB  - We investigated the association of the -11,391G>A, -11,377G>C, +45T>G, and
      +276G>T adiponectin single-nucleotide polymorphisms (SNPs) and expected
      haplotypes with the insulin resistance (IR) state in overweight/obese children;
      by using the haplotype background analysis, we also assessed the effect of each
      SNP independently. GG genotype at the -11,391 locus was associated with higher
      fasting insulin levels and homeostasis model assessment-IR index and lower
      adiponectin levels compared with GA + AA genotypes (p = 0.01, 0.002, and 0.03,
      respectively). Those heterozygous and homozygous for G allele at the -11,377
      locus showed higher fasting glucose (p = 0.001 for both), fasting insulin (p =
      0.001 for both), homeostasis model assessment-IR index (p < 0.001 for both), and
      triglyceride levels (p = 0.02 and 0.03, respectively) and lower adiponectin
      levels (p = 0.002 and 0.02, respectively) compared with C homozygotes. The +45G
      carriers showed higher fasting and 2-hour glucose levels (p = 0.01 for both) and
      lower adiponectin levels (p = 0.02) compared with non-carriers. Haplotype
      analysis suggested that, considering the same haplotypic background, each of the
      three polymorphisms exerted an independent effect on investigated parameters. The
      -11,391G>A, -11,377C>G, and +45T>G SNPs are associated with IR syndrome in
      overweight/obese children; they independently influence the investigated
      variables. The effect of +45T>G SNP seems to be marginal compared with the
      promoter SNPs. The GGT haplotype is associated with the highest degree of IR.

PMID- 17030960
TI  - Adiponectin and membrane fluidity of erythrocytes in normotensive and
      hypertensive men.
AB  - OBJECTIVE: Abnormalities in physicochemical properties of the cell membranes may
      underlie the defects that are strongly linked to hypertension. Recent evidence
      indicates that adiponectin may have protective effects against cardiovascular
      diseases. The purpose of the present study was to assess the possible link
      between plasma adiponectin and membrane fluidity in normotensive (NT) and
      hypertensive (HT) men. RESEARCH METHODS AND PROCEDURES: We measured the membrane
      fluidity (a reciprocal value of membrane microviscosity) of erythrocytes in NT
      and HT men by using an electron paramagnetic resonance and spin-labeling method.
      RESULTS: The order parameter (S) for the spin label agent (5-nitroxide stearate)
      and the peak height ratio (h0/h(-1)) for 16-nitroxide stearate in the electron
      paramagnetic resonance spectra of erythrocytes were significantly higher in HT
      men than in NT men, indicating that membrane fluidity of erythrocytes was
      decreased in HT men compared with NT men. Both of plasma adiponectin and nitric
      oxide (NO) metabolite levels were significantly lower in HT men than in NT men.
      The plasma adiponectin levels were correlated with plasma NO metabolites. The S
      and the h0/h(-1) of erythrocytes were inversely correlated with the plasma
      adiponectin and NO metabolite levels, indicating that the decreased membrane
      fluidity of erythrocytes was associated with hypoadiponectinemia and reduced
      plasma NO metabolites. DISCUSSION: The results of the present study demonstrated
      that plasma adiponectin levels were lower in HT men than in NT men and that
      hypoadiponectinemia was associated with decreased membrane fluidity of
      erythrocytes. The finding suggests that adiponectin may be linked to the
      rheologic behavior of the erythrocytes and the microcirculation in men, at least
      in part, by the NO-dependent mechanism.

PMID- 17030961
TI  - High-molecular weight adiponectin isoforms increase after biliopancreatic
      diversion in obese subjects.
AB  - OBJECTIVE: Our objective was to test the effect of biliopancreatic diversion
      (BDP) in adiponectin multimerization. Adiponectin, the major protein secreted by
      adipose tissue, circulates in plasma in different isoforms. The most clinically
      relevant oligomers are high-molecular weight (HMW) multimers and low-molecular
      weight (LMW) trimers. Contrasting data on the effect of weight loss on
      adiponectin isoforms have been reported. RESEARCH METHODS AND PROCEDURES: We
      measured total plasma adiponectin and HMW and LMW adiponectin oligomers (by
      Western blot analysis) before and 1 month after BPD, in 18 severely obese
      subjects. RESULTS: One month after BPD, body weight decreased approximately 11%.
      Total adiponectin showed significant increase after BPD. In addition, we found a
      significant increase in HMW (percentage) adiponectin oligomers. We found a
      significant inverse correlation between HMW (percentage) and BMI before and after
      BPD. Homeostasis model of assessment-insulin resistance decreased significantly
      after the BPD, without any significant correlation with total serum adiponectin
      and adiponectin oligomers. DISCUSSION: A moderate weight loss after BPD increases
      total and HMW adiponectin oligomers. The significant correlation between BMI and
      HMW (percentage) adiponectin oligomers but not between BMI and total adiponectin
      might indicate a role of body fat mass in regulation of adiponectin
      multimerization. These data suggest that HMW oligomers represent a very sensitive
      parameter to short-term BMI changes after BPD.

PMID- 17030962
TI  - 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective
      changes in body weight and insulin resistance.
AB  - OBJECTIVE: Increased mRNA and activity levels of 11beta-hydroxysteroid
      dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated
      with obesity and insulin resistance. The aim of our study was to investigate
      whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non
      diabetic subjects are associated with subsequent changes in body weight and
      insulin resistance [homeostasis model assessment of insulin resistance (HOMA
      IR)]. RESEARCH METHODS AND PROCEDURES: Prospective analyses were performed in 20
      subjects (two whites and 18 Pima Indians) who had baseline measurements of
      11betaHSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47
      Pima Indians who had baseline assessments of 11betaHSD1 mRNA in isolated
      adipocytes (follow-up, 0.8 to 5.3 years). RESULTS: In whole AT, although
      11betaHSD1 mRNA levels showed positive associations with changes in weight and
      HOMA-IR, 11betaHSD1 activity was associated with changes in HOMA-IR but not in
      body weight. 11betaHSD1 mRNA levels in isolated adipocytes were not associated
      with follow-up changes in any of the anthropometric or metabolic variables.
      DISCUSSION: Our results indicate that increased expression of 11betaHSD1 in
      subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin
      resistance. This prospective relationship does not seem to be mediated by
      increased 11betaHSD1 expression in adipocytes.

PMID- 17030963
TI  - Effects of resistant starch, a non-digestible fermentable fiber, on reducing body
      fat.
AB  - OBJECTIVE: To assess the effects of energy dilution with non-fermentable and
      fermentable fibers on abdominal fat and gut peptide YY (PYY) and glucagon-like
      peptide (GLP)-1 expressions, three rat studies were conducted to: determine the
      effects of energy dilution with a non-fermentable fiber, compare similar fiber
      levels of fermentable and non-fermentable fibers, and compare similar
      metabolizable energy dilutions with fermentable and non-fermentable fibers.
      RESEARCH METHODS AND PROCEDURES: In Study 1, rats were fed one of three diets
      with different metabolizable energy densities. In Study 2, rats were fed diets
      with similar fiber levels using high amylose-resistant cornstarch (RS) or
      methylcellulose. In Study 3, rats were fed diets with a similar dilution of
      metabolizable energy using cellulose or RS. Measurements included food intake,
      body weight, abdominal fat, plasma PYY and GLP-1, gastrointestinal tract weights,
      and gene transcription of PYY and proglucagon. RESULTS: Energy dilution resulted
      in decreased abdominal fat in all studies. In Study 2, rats fed fermentable RS
      had increased cecal weights and plasma PYY and GLP-1, and increased gene
      transcription of PYY and proglucagon. In Study 3, RS-fed rats had increased short
      chain fatty acids in cecal contents, plasma PYY (GLP-1 not measured), and gene
      transcription for PYY and proglucagon. DISCUSSION: Inclusion of RS in the diet
      may affect energy balance through its effect as a fiber or a stimulator of PYY
      and GLP-1 expression. Increasing gut hormone signaling with a bioactive
      functional food such as RS may be an effective natural approach to the treatment
      of obesity.

PMID- 17030964
TI  - Thermoregulatory control of feeding and sleep in premature infants.
AB  - OBJECTIVE: The aim of the present study was to test the thermoregulatory feeding
      control hypothesis in sleeping, premature infants. RESEARCH METHODS AND
      PROCEDURES: In premature infants, the energy supply from food intake is crucial
      for (in order of importance): organ operation, body homeothermia, and optimal
      growth. The Himms-Hagen model of thermoregulatory feeding control involving
      activation of heat production by brown adipose tissue (BAT) was formulated on the
      basis of work in (awake) rats. This hypothesis has also been put forward for the
      human neonate, which can also use BAT to produce metabolic heat. According to the
      model, feeding episodes occur during a transient increase in body temperature.
      Feeding is initiated by a dip in blood glucose concentration after sugar uptake
      by activated BAT. RESULTS: In 14 neonates (bottle-fed on demand), food intake
      always took place during an increase in skin temperature (+0.19 +/- 0.21 degrees
      C). Awakening occurred 18 +/- 17 minutes after the minimum skin temperature level
      had been reached. When feeding time was imposed, feeding was not necessarily
      situated during an increase in skin temperature, and the sleep duration after
      food intake increased significantly (+43%). This could be considered as an
      adaptive response to the short-term sleep deprivation and/or stress elicited by
      an imposed feeding rhythm. DISCUSSION: The validity of the model supports the use
      of on-demand feeding in neonatal care units, in accordance with the infant's
      physiological body temperature oscillations.

PMID- 17030966
TI  - Differential effects of gastric bypass and banding on circulating gut hormone and
      leptin levels.
AB  - OBJECTIVE: To quantify plasma concentrations of hormones that regulate energy
      homeostasis in order to establish possible mechanisms for greater weight loss
      after Roux-en-Y gastric bypass (RYGBP) compared with gastric banding (BND).
      RESEARCH METHODS AND PROCEDURES: Four groups of women were studied: lean (n = 8;
      mean BMI, 21.6 kg/m2); BND (n = 9; BMI, 35.8; 25% weight loss), RYGBP (n = 9;
      BMI, 34.2; 36% weight loss), and controls matched for BMI to the surgical groups
      (n = 11; BMI, 34.4). RESULTS: Fasting total peptide YY (PYY) and PYY(3-36)
      immunoreactivity were similar among all groups, but the postprandial response in
      the RYGBP group was exaggerated, such that 30 minutes after the meal, total and
      PYY(3-36) levels were 2- to 4-fold greater compared with all other groups.
      Maximal postprandial suppression of total ghrelin was blunted in the BND group
      (13%) compared with RYGBP (27%). Postprandial suppression of octanoylated ghrelin
      was also less in BND (29%) compared with RYGBP (56%). Fasting insulin was lower
      in RYGBP (6.6 microU/mL) compared with BND (10.0 microU/mL). Compared with lean
      controls, leptin concentrations were significantly higher in BND but not in
      RYGBP. There was a greater increase in post-meal satiety in the RYGBP group
      compared with BND and overweight controls. DISCUSSION: The differences between
      RYGBP and BND subjects in postprandial concentrations of PYY and ghrelin would be
      expected to promote increased satiety and earlier meal termination in RYGBP and
      may aid in greater weight loss. The differences in insulin and leptin
      concentrations associated with these procedures may also reflect differences in
      insulin sensitivity and energy partitioning.

PMID- 17030967
TI  - Physiological evidence for the involvement of peptide YY in the regulation of
      energy homeostasis in humans.
AB  - OBJECTIVE: To explore the potential role of the endogenous peptide YY (PYY) in
      the long-term regulation of body weight and energy homeostasis. RESEARCH METHODS
      AND PROCEDURES: Fasting and postprandial plasma PYY concentrations were measured
      after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21
      men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4
      months later. Ratings of hunger and satiety were collected using visual analog
      scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ)
      were assessed using a respiratory chamber. RESULTS: Fasting PYY concentrations
      were negatively correlated with various markers of adiposity and negatively
      associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY
      (area under the curve) were positively associated with postprandial changes in
      ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved
      after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41,
      p = 0.03). Prospectively, the peak PYY concentrations were negatively associated
      with changes in body weight (r = -0.58, p = 0.01). DISCUSSION: Our data indicate
      that the endogenous PYY may be involved in the long-term regulation of body
      weight. It seems that this long-term effect was not exclusively driven by the
      modulation of food intake but also by the control of energy expenditure and lipid
      metabolism.

PMID- 17030965
TI  - Decreased expression of adipogenic genes in obese subjects with type 2 diabetes.
AB  - OBJECTIVE: Our objective was to delineate the potential role of adipogenesis in
      insulin resistance and type 2 diabetes. Obesity is characterized by an increase
      in adipose tissue mass resulting from enlargement of existing fat cells
      (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The
      inability of the adipose tissue to recruit new fat cells may cause ectopic fat
      deposition and insulin resistance. RESEARCH METHODS AND PROCEDURES: We examined
      the expression of candidate genes involved in adipocyte proliferation and/or
      differentiation [CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA
      domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated
      receptor (PPAR) gamma2, signal transducer and activator of transcription 5A
      (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding
      protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin
      related protein (PGAR), insulin-like growth factor 1, PPARgamma coactivator
      1alpha, PPARgamma coactivator 1beta, and PPARdelta] in subcutaneous adipose
      tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic
      subjects matched for age and obesity. RESULTS: Insulin sensitivity was measured
      by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As
      expected, subjects with type 2 diabetes had lower glucose disposal (4.9 +/- 1.9
      vs. 7.5 +/- 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat
      cells (0.90 +/- 0.26 vs. 0.78 +/- 0.17 microm; p = 0.04) as compared with obese
      control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and
      PPARgamma2, p = 0.02) had significantly lower expression in obese type 2
      diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07). DISCUSSION: This
      cross-sectional study supports the hypothesis that impaired expression of
      adipogenic genes may result in impaired adipogenesis, potentially leading to
      larger fat cells in subcutaneous adipose tissue and insulin resistance.

PMID- 17030968
TI  - Associations between aortic calcification and components of body composition in
      elderly men.
AB  - OBJECTIVE: To investigate associations among body composition, cardiovascular
      risk factors, and atherosclerosis in middle-aged and elderly men for the
      identification of potential pathogenic links. RESEARCH METHODS AND PROCEDURES:
      The study included 168 white men 44 to 86 years old. Severity of aortic
      calcification (AC) was graded on lateral radiographs, and body fat and lean mass
      were measured by DXA. Information on demographic and lifestyle characteristics
      also was gathered. RESULTS: A strong and independent inverse association was
      found between AC and peripheral lean mass (PLM), even after adjusting for age and
      BMI (p < 0.05). Independently of the influence of PLM, AC was directly correlated
      with truncal fat mass (p < 0.05). Furthermore, AC was inversely associated with
      tertiles of the free androgen index (p < 0.05). In a multiple regression model,
      age and serum cholesterol (p < 0.01) contributed directly, and truncal fat mass
      tended also to contribute directly (p = 0.09), whereas PLM contributed borderline
      inversely (p = 0.06) to the variation of AC (R = 0.635, p < 0.0001). DISCUSSION:
      Severity of AC is strongly dependent on age and further modulated by an array of
      traditional cardiovascular risk factors. Sarcopenia and truncal fat mass are
      reciprocal correlates of atherosclerosis of borderline statistical significance
      in multivariate models. To clarify whether sarcopenia is an atherogenic risk
      factor or rather a parallel consequence of low-grade inflammation also promoting
      atherogenic trends, further longitudinal studies in larger sample sizes of men
      and women are needed.

PMID- 17030969
TI  - Cardiorespiratory fitness in youth: relationship to insulin sensitivity and beta
      cell function.
AB  - OBJECTIVE: We examined whether the relationship between cardiorespiratory fitness
      (CRF) and insulin sensitivity (IS)/secretion is independent of adiposity in
      healthy African-American (n = 65) and white (n = 57) youth. RESEARCH METHODS AND
      PROCEDURES: IS and beta-cell function were evaluated by a 3-hour hyperinsulinemic
      euglycemic and a 2-hour hyperglycemic (12.5 mM) clamp, respectively. Total fat
      was measured by DXA and abdominal fat with computed tomography. CRF (peak volume
      of oxygen) was measured using a graded maximal treadmill test. RESULTS:
      Independent of race, CRF was inversely (p < 0.05) related to total and abdominal
      fat, fasting insulin and first phase insulin secretion, and positively (p < 0.05)
      related to IS. When subjects were categorized into low (< or = 50th) and high (>
      50th) CRF groups, IS was significantly (p < 0.05) higher in the high compared
      with the low CRF group independently of race. Furthermore, first and second phase
      insulin secretion were lower (p < 0.05) in the high CRF group in comparison with
      the low CRF group in both races. However, in multiple regression analyses CRF was
      not (p > 0.05) an independent predictor of IS and acute insulin secretion after
      accounting for total adiposity. DISCUSSION: Our findings demonstrate that low CRF
      is associated with decreased IS compensated by higher insulin secretion in both
      African-American and white youth. However, this relationship disappears after
      adjusting for differences in adiposity, suggesting that the association between
      fitness and IS is mediated, at least in part, through fatness.

PMID- 17030970
TI  - Angiotensin-converting enzyme inhibition reduces lipid deposits in myocardium and
      improves left ventricular function of obese zucker rats.
AB  - OBJECTIVE: Alterations in the renin angiotensin system, cardiac lipotoxicity, and
      left ventricular (LV) dysfunction have been reported in obese rats. The present
      study examined whether angiotensin-converting enzyme inhibition could ameliorate
      lipid deposition and ventricular function in the myocardium of obese Zucker rats
      (OZRs). RESEARCH METHODS AND PROCEDURES: For 6 months, rats were treated as
      follows: Group (G) 1, OZR, no treatment; G2, OZR + ramipril (R); G3, OZR +
      amlodipine (AML); and G4, lean Zucker rats. LV function was assessed by
      echocardiogram and lipid deposits in cardiomyocytes (LDCM) by light microscopy
      using Oil red O. RESULTS: At the end of the experiment, both OZR + R and OZR +
      AML groups presented similar reduction in blood pressure in comparison with
      untreated OZR (p < 0.01). OZR with R presented lower insulin-to-glucose ratio and
      lower serum triglycerides and cholesterol when compared with both untreated OZR
      and OZR with AML (p < 0.01). Fractional shortening by echocardiogram was as
      follows: G1, 25.4 +/- 3.8 (vs. G2 and G4, p < 0.05); G2, 37.2 +/- 2.4; G3, 29.3
      +/- 4.4 (vs. G2 and G4, p < 0.05); and G4, 40.8 +/- 2.3. Percentage LDCM was as
      follows: G1, 12.4 +/- 2.7 (vs. G2 and G4, p < 0.05); G2, 0.8 +/- 0.2; G3, 11.1 +/
      2.1 (vs. G2 and G4, p < 0.05); and G4, 0.1 +/- 0.1. There was a negative
      correlation between fractional shortening and LDCM percentage in OZR (r = -0.93)
      and in OZR + AML (r = -0.87). DISCUSSION: AML reduced blood pressure
      significantly; however, it failed to modify both metabolic parameters and LDCM.
      In contrast, R showed a substantial reduction in LDCM, together with LV function
      preservation.

PMID- 17030971
TI  - A quantitative trait locus on chromosome 18q for physical activity and dietary
      intake in Hispanic children.
AB  - OBJECTIVE: Genetic components of energy homeostasis contributing to childhood
      obesity are poorly understood. Genome scans were performed to identify
      chromosomal regions contributing to physical activity and dietary intake traits
      in Hispanic children participating in the VIVA LA FAMILIA Study. RESEARCH METHODS
      AND PROCEDURES: We report linkage findings on chromosome 18 for physical activity
      and dietary intake in 1030 siblings from 319 Hispanic families. Measurements
      entailed physical activity by accelerometry, dietary intake by two 24-hour
      recalls, and genetic linkage analyses using SOLAR software. RESULTS: Significant
      heritabilities were seen for physical activity and dietary intake, ranging from
      0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in
      sedentary activity mapped to markers D18S1102-D18S64 on chromosome 18 [logarithm
      of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R)
      resides. Quantitative trait loci (QTLs) for total activity counts, percentage
      time in light or in moderate activity, and carbohydrate intake and percentage of
      energy intake from carbohydrates were detected in the same region (LOD = 2.28,
      2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in
      MC4R (G55V) was detected in six obese relatives, but not in the rest of the
      cohort. Removal of these MC4R-deficient subjects from the analysis reduced the
      LOD score for sedentary activity to 3.94. DISCUSSION: Given its role in the
      regulation of food intake and energy expenditure, MC4R is a strong positional
      candidate gene for the QTL on chromosome 18 detected for physical activity and
      dietary intake in Hispanic children.

PMID- 17030972
TI  - A quantitative trait locus for body fat on chromosome 1q43 in French Canadians:
      linkage and association studies.
AB  - OBJECTIVE: To explore a quantitative trait locus (QTL) on human chromosome 1q
      affecting BMI, adiposity, and fat-free mass phenotypes in the Quebec Family Study
      cohort. RESEARCH METHODS AND PROCEDURES: Non-parametric sibpair and variance
      component linkage analyses and family-based association studies were performed
      with a dense set of chromosome 1q43 microsatellites and single-nucleotide
      polymorphism markers in 885 adult individuals. RESULTS: Linkage was observed
      between marker D1S184 and BMI (p = 0.0004) and with body fat mass or percentage
      body fat (p < or = 0.0003), but no linkage was detected with fat-free mass.
      Furthermore, significant linkages (p < 0.0001) were achieved with subsamples of
      sibpairs at both ends of phenotype distributions. Association studies with
      quantitative transmission disequilibrium tests refined the linkage to a region
      overlapping the regulator of G-protein signaling 7 (RGS7) gene and extending to
      immediate upstream gene loci. DISCUSSION: The present study indicates that the
      QTL on chromosome 1q43 specifically affects total adiposity and provides a
      genetic mapping framework for the dissection of this adiposity locus.

PMID- 17030973
TI  - Hip-Hop to Health Jr. for Latino preschool children.
AB  - OBJECTIVE: Hip-Hop to Health Jr. was a diet/physical activity intervention
      designed to reduce gains in BMI (kilograms per meter squared) in preschool
      minority children. RESEARCH METHODS AND PROCEDURES: Twelve predominantly Latino
      Head Start centers participated in a group-randomized trial conducted between
      Fall 2001 and Winter 2003. Six centers were randomized to a culturally proficient
      14-week (three times weekly) diet/physical activity intervention. Parents
      participated by completing weekly homework assignments. The children in the other
      six centers received a general health intervention that did not address either
      diet or physical activity. The primary outcome was change in BMI, and secondary
      outcomes were changes in dietary intake and physical activity. Measures were
      collected at baseline, post-intervention, and at Years 1 and 2 follow-up.
      RESULTS: There were no significant differences between intervention and control
      schools in either primary or secondary outcomes at post-intervention, Year 1, or
      Year 2 follow-ups. DISCUSSION: When Hip-Hop to Health Jr. was conducted in
      predominantly black Head Start centers, it was effective in reducing subsequent
      increases in BMI in preschool children. In contrast, when the program was
      conducted in Latino centers, it was not effective. Although the intervention did
      not prevent excessive weight gain in Latino children, it was very well received.
      Future interventions with this population may require further cultural tailoring
      and a more robust parent intervention.

PMID- 17030974
TI  - Body image and quality of life in post massive weight loss body contouring
      patients.
AB  - OBJECTIVE: Because post-bariatric surgery patients undergo massive weight loss,
      the resulting skin excess can lead to both functional problems and profound
      dissatisfaction with appearance. Correcting skin excess could improve all these
      corollaries, including body image. Presently, few data are available documenting
      body image and weight-related quality of life in this population. RESEARCH
      METHODS AND PROCEDURES: Eighteen patients who underwent both bariatric surgery
      and body contouring completed our study. Both established surveys and new surveys
      designed specifically for the study were used to assess body perception and
      ideals, quality of life, and mood. Patients were surveyed at the following time
      points: pre-body contouring (after massive weight loss) and both 3 and 6 month
      post-body contouring. Statistical testing was performed using Student's t test
      and ANOVA. RESULTS: The mean age of the patients was 46 +/- 10 years (standard
      deviation). Quality of life improved after obesity surgery and was significantly
      enhanced after body contouring. Three months after body contouring, subjects
      ascribed thinner silhouettes to both current appearance and ideal body image.
      Body image also improved with body contouring surgery. Mood remained stable over
      6 months. DISCUSSION: Body contouring after surgical weight loss improved both
      quality-of-life measurements and body image. Initial body dissatisfaction did not
      correlate with mood. Body contouring improved body image but produced
      dissatisfaction with other parts of the body, suggesting that as patients become
      closer to their ideal, these ideals may shift. We further developed several new
      assessment methods that may prove useful in understanding these post-surgical
      weight loss patients.

PMID- 17030975
TI  - Long-term effects of obesity on employment and work limitations among U.S.
      Adults, 1986 to 1999.
AB  - OBJECTIVE: To determine the relationships between BMI and workforce participation
      and the presence of work limitations in a U.S. working-age population. RESEARCH
      METHODS AND PROCEDURES: We used data from the Panel Study of Income Dynamics, a
      nationwide prospective cohort, to estimate the effect of obesity in 1986 on
      employment and work limitations in 1999. Individuals were classified into the
      following weight categories: underweight (BMI < 18.5), normal weight (18.5 < or =
      BMI < 25), overweight (25 < or = BMI < 30), and obese (BMI > or = 30). Using
      multivariable probit models, we estimated the relationships between obesity and
      both employment and work disability. All analyses were stratified by sex.
      RESULTS: After adjusting for baseline sociodemographic characteristics, smoking
      status, exercise, and self-reported health, obesity was associated with reduced
      employment at follow-up [men: marginal effect (ME) -4.8 percentage points (pp); p
      < 0.05; women: ME -5.8 pp; p < 0.10]. Among employed women, being either
      overweight or obese was associated with an increase in self-reported work
      limitations when compared with normal-weight individuals (overweight: ME +3.9 pp;
      p < 0.01; obese: ME +12.6 pp; p < 0.01). Among men, the relationship between
      obesity and work limitations was not statistically significant. DISCUSSION:
      Obesity appears to result in future productivity losses through reduced workforce
      participation and increased work limitations. These findings have important
      implications in the U.S., which is currently experiencing a rise in the
      prevalence of obesity.

PMID- 17030976
TI  - Maternal corticotropin-releasing hormone levels during pregnancy and offspring
      adiposity.
AB  - OBJECTIVE: Animal models suggest that fetal exposure to glucocorticoids can
      program adiposity, especially central adiposity, later in life. We examined
      associations of maternal corticotropin-releasing hormone (CRH) levels in the late
      2nd trimester of pregnancy, a marker of fetal glucocorticoid exposure, with child
      adiposity at age 3 years. RESEARCH METHODS AND PROCEDURES: We analyzed data from
      199 participants in Project Viva, a prospective cohort study of pregnant women
      and their children, At age 3 years, the main outcomes were age-sex-specific BMI z
      score and the sum of subscapular (SS) and triceps (TR) skinfold thicknesses to
      represent overall adiposity, and ratio of SS to TR (SS:TR) to represent central
      adiposity. RESULTS: Mean (standard deviation) maternal 2nd trimester log CRH was
      4.94 (0.56) pg/mL. At age 3, mean (standard deviation) for BMI z score was 0.52
      (1.02); for SS + TR, 16.51 (3.94) mm; and for SS:TR, 0.67 (0.17). Log CRH was
      mildly inversely correlated with birth weight (r = -0.08), chiefly because of its
      association with length of gestation (r = -0.21) rather than fetal growth (r = 
      0.004). After adjustment for sociodemographic factors, maternal smoking, BMI, and
      gestational weight gain, fetal growth, length of gestation, breastfeeding
      duration, and (for SS:TR only) child's 3-year BMI, each increment of 1 unit of
      log CRH was associated with a reduction in BMI z score [-0.43; 95% confidence
      interval (CI), -0.73, -0.14; p = 0.004] and possible reduction in SS + TR (-1.10;
      95% CI, -2.33, 0.14; p = 0.08). In contrast, log CRH was associated with higher
      SS:TR (0.07; 95% CI, 0.02, 0.13; p = 0.007). DISCUSSION: Fetal exposure to
      glucocorticoids, although associated with an overall decrease in body size, may
      cause an increase in central adiposity.

PMID- 17030977
TI  - Impaired lung function is associated with obesity and metabolic syndrome in
      adults.
AB  - OBJECTIVE: Impaired lung function is associated with obesity and insulin
      resistance. In this study, we investigated the relationship between metabolic
      syndrome and impaired lung function in adults. RESEARCH METHODS AND PROCEDURES: A
      total of 46,514 subjects 20 years and over (21,669 men and 24,845 women, mean age
      = 37.3 +/- 11.2 and 37.0 +/- 11.3 years, respectively) were recruited from four
      nationwide MJ Health Screening Centers in Taiwan from 1998 to 2000. Metabolic
      syndrome was defined using the National Cholesterol Education Panel (NCEP)
      metabolic syndrome criteria or America Heart Association/National Heart Lung
      Blood Institute (AHA/NHLBI) criteria. The relationship between metabolic syndrome
      and lung function test was examined using multivariate logistic regression
      analysis. RESULTS: The prevalence of impaired lung function was 11.1% in men and
      14.0% in women. The prevalence of metabolic syndrome was 5.8% using NCEP criteria
      and 12.8% using AHA/NHLBI criteria. In multivariate logistic regression analysis
      with adjustment for age, gender, BMI, smoking, alcohol drinking, and physical
      activity, restrictive lung impairment was independently associated with increased
      risk of having metabolic syndrome (p < 0.01, odds ratios = 1.221 using NCEP
      criteria and 1.150 using AHA/NHLBI criteria). DISCUSSION: Obesity and metabolic
      syndrome were associated with impaired lung function in adults in Taiwan. Our
      results imply that obesity and insulin resistance may be the common pathways
      underlying lung function impairment and metabolic syndrome. Moreover, lung
      function test may be applied as an additional evaluation for metabolic syndrome
      in a clinical setting.

PMID- 17030978
TI  - Relation of BMI and physical activity to sex hormones in postmenopausal women.
AB  - OBJECTIVE: Levels of estrogen, androgen, and prolactin have been related to risk
      of postmenopausal breast cancer. However, the determinants of these hormone
      concentrations are not established. The purpose of this study was to examine
      correlates of endogenous sex hormones. RESEARCH METHODS AND PROCEDURES:
      Associations among adiposity, physical activity, and diet and concentrations of
      estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone
      binding globulin (SHBG), androstenedione, dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, and prolactin were evaluated in 267
      postmenopausal women randomly selected from the Women's Health Initiative Dietary
      Modification Trial. RESULTS: In multiple regression analyses on log-transformed
      hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001),
      estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001),
      free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p =
      0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total
      physical activity (metabolic equivalent tasks per week) was negatively associated
      with concentrations of estrone, estradiol, and androstenedione (beta = -0.006, 
      0.007, and -0.005, respectively, all p < or = 0.05). Using a composite variable
      of BMI and physical activity dichotomized by median values, women with high
      BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL,
      compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical
      activity, low BMI/low physical activity, and low BMI/high physical activity,
      respectively (p trend < 0.001). Similar trends were observed for estradiol and
      free estradiol and, in inverse, for SHBG. DISCUSSION: These associations may, in
      part, explain the positive associations between overweight/obesity and a
      sedentary lifestyle on breast cancer risk.

PMID- 17030979
TI  - Full of sound and fury, but signifying something: XVI International AIDS
      Conference, Toronto, Canada, August 13-18, 2006.
AB  - The biennial AIDS conference is often exhausting and irritating, but it offers a
      unique view of how science and society interact. It still deserves the support of
      basic scientists.

PMID- 17030980
TI  - Dynamic microtubules are essential for efficient chromosome capture and
      biorientation in S. cerevisiae.
AB  - Attachment of chromosomes to the mitotic spindle has been proposed to require
      dynamic microtubules that randomly search three-dimensional space and become
      stabilized upon capture by kinetochores. In this study, we test this model by
      examining chromosome capture in Saccharomyces cerevisiae mutants with attenuated
      microtubule dynamics. Although viable, these cells are slow to progress through
      mitosis. Preanaphase cells contain a high proportion of chromosomes that are
      attached to only one spindle pole and missegregate in the absence of the spindle
      assembly checkpoint. Measurement of the rates of chromosome capture and
      biorientation demonstrate that both are severely decreased in the mutants. These
      results provide direct evidence that dynamic microtubules are critical for
      efficient chromosome capture and biorientation and support the hypothesis that
      microtubule search and capture plays a central role in assembly of the mitotic
      spindle.

PMID- 17030981
TI  - Mapping the assembly pathways that specify formation of the trilaminar
      kinetochore plates in human cells.
AB  - We report the interactions amongst 20 proteins that specify their assembly to the
      centromere-kinetochore complex in human cells. Centromere protein (CENP)-A is at
      the top of a hierarchy that directs three major pathways, which are specified by
      CENP-C, -I, and Aurora B. Each pathway consists of branches that intersect to
      form nodes that may coordinate the assembly process. Complementary EM studies
      found that the formation of kinetochore trilaminar plates depends on the CENP
      I/NUF2 branch, whereas CENP-C and Aurora B affect the size, shape, and structural
      integrity of the plates. We found that hMis12 is not constitutively localized at
      kinetochores, and that it is not essential for recruiting CENP-I. Our studies
      also revealed that kinetochores in HeLa cells contain an excess of CENP-A, of
      which approximately 10% is sufficient to promote the assembly of normal levels of
      kinetochore proteins. We elaborate on a previous model that suggested
      kinetochores are assembled from repetitive modules (Zinkowski, R.P., J. Meyne,
      and B.R. Brinkley. 1991. J. Cell Biol. 113:1091-110).

PMID- 17030982
TI  - Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response
      to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and
      ATR.
AB  - The promyelocytic leukemia (PML) nuclear body (NB) is a dynamic subnuclear
      compartment that is implicated in tumor suppression, as well as in the
      transcription, replication, and repair of DNA. PML NB number can change during
      the cell cycle, increasing in S phase and in response to cellular stress,
      including DNA damage. Although topological changes in chromatin after DNA damage
      may affect the integrity of PML NBs, the molecular or structural basis for an
      increase in PML NB number has not been elucidated. We demonstrate that after DNA
      double-strand break induction, the increase in PML NB number is based on a
      biophysical process, as well as ongoing cell cycle progression and DNA repair.
      PML NBs increase in number by a supramolecular fission mechanism similar to that
      observed in S-phase cells, and which is delayed or inhibited by the loss of
      function of NBS1, ATM, Chk2, and ATR kinase. Therefore, an increase in PML NB
      number is an intrinsic element of the cellular response to DNA damage.

PMID- 17030983
TI  - Visualization of mRNA translation in living cells.
AB  - The role of mRNA localization is presumably to effect cell asymmetry by
      synthesizing proteins in specific cellular compartments. However, protein
      synthesis has never been directly demonstrated at the sites of mRNA localization.
      To address this, we developed a live cell method for imaging translation of beta
      actin mRNA. Constructs coding for beta-actin, containing tetracysteine motifs,
      were transfected into C2C12 cells, and sites of nascent polypeptide chains were
      detected using the biarsenial dyes FlAsH and ReAsH, a technique we call
      translation site imaging. These sites colocalized with beta-actin mRNA at the
      leading edge of motile myoblasts, confirming that they were translating. beta
      Actin mRNA lacking the sequence (zipcode) that localizes the mRNA to the cell
      periphery, eliminated the translation there. A pulse-chase experiment on living
      cells showed that the recently synthesized protein correlated spatially with the
      sites of its translation. Additionally, localization of beta-actin mRNA and
      translation activity was enhanced at cell contacts and facilitated the formation
      of intercellular junctions.

PMID- 17030984
TI  - MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.
AB  - Terminal differentiation of distinct cell types requires the transcriptional
      activation of differentiation-specific genes and the suppression of genes
      associated with the precursor cell. For example, the expression of utrophin
      (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced
      at the sarcolemma by the related dystrophin protein. The MyoD transcription
      factor directly activates the expression of a large number of skeletal muscle
      genes, but also suppresses the expression of many genes. To characterize a
      mechanism of MyoD-mediated suppression of gene expression, we investigated two
      genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD,
      follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a
      muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1
      and Utrn RNA, and these sequences are sufficient to suppress gene expression in
      the presence of miR-206. These findings demonstrate that MyoD, in addition to
      activating muscle-specific genes, induces miRNAs that repress gene expression
      during skeletal muscle differentiation.

PMID- 17030985
TI  - Shootin1: A protein involved in the organization of an asymmetric signal for
      neuronal polarization.
AB  - Neurons have the remarkable ability to polarize even in symmetrical in vitro
      environments. Although recent studies have shown that asymmetric intracellular
      signals can induce neuronal polarization, it remains unclear how these polarized
      signals are organized without asymmetric cues. We describe a novel protein, named
      shootin1, that became up-regulated during polarization of hippocampal neurons and
      began fluctuating accumulation among multiple neurites. Eventually, shootin1
      accumulated asymmetrically in a single neurite, which led to axon induction for
      polarization. Disturbing the asymmetric organization of shootin1 by excess
      shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited
      polarization. Overexpression and RNA interference data suggest that shootin1 is
      required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was
      transported anterogradely to the growth cones and diffused back to the soma;
      inhibiting this transport prevented its asymmetric accumulation in neurons. We
      propose that shootin1 is involved in the generation of internal asymmetric
      signals required for neuronal polarization.

PMID- 17030986
TI  - Embryonic cortical neural stem cells migrate ventrally and persist as postnatal
      striatal stem cells.
AB  - Embryonic cortical neural stem cells apparently have a transient existence, as
      they do not persist in the adult cortex. We sought to determine the fate of
      embryonic cortical stem cells by following Emx1(IREScre); LacZ/EGFP double
      transgenic murine cells from midgestation into adulthood. Lineage tracing in
      combination with direct cell labeling and time-lapse video microscopy
      demonstrated that Emx1-lineage embryonic cortical stem cells migrate ventrally
      into the striatal germinal zone (GZ) perinatally and intermingle with striatal
      stem cells. Upon integration into the striatal GZ, cortical stem cells down
      regulate Emx1 and up-regulate Dlx2, which is a homeobox gene characteristic of
      the developing striatum and striatal neural stem cells. This demonstrates the
      existence of a novel dorsal-to-ventral migration of neural stem cells in the
      perinatal forebrain.

PMID- 17030987
TI  - Transient anchorage of cross-linked glycosyl-phosphatidylinositol-anchored
      proteins depends on cholesterol, Src family kinases, caveolin, and
      phosphoinositides.
AB  - How outer leaflet plasma membrane components, including glycosyl
      phosphatidylinositol-anchored proteins (GPIAPs), transmit signals to the cell
      interior is an open question in membrane biology. By deliberately cross-linking
      several GPIAPs under antibody-conjugated 40-nm gold particles, transient
      anchorage of the gold particle-induced clusters of both Thy-1 and CD73, a 5'
      exonucleotidase, occurred for periods ranging from 300 ms to 10 s in fibroblasts.
      Transient anchorage was abolished by cholesterol depletion, addition of the Src
      family kinase (SFK) inhibitor PP2, or in Src-Yes-Fyn knockout cells. Caveolin-1
      knockout cells exhibited a reduced transient anchorage time, suggesting the
      partial participation of caveolin-1. In contrast, a transmembrane protein, the
      cystic fibrosis transmembrane conductance regulator, exhibited transient
      anchorage that occurred without deliberately enhanced cross-linking; moreover, it
      was only slightly inhibited by cholesterol depletion or SFK inhibition and
      depended completely on the interaction of its PDZ-binding domain with the
      cytoskeletal adaptor EBP50. We propose that cross-linked GPIAPs become
      transiently anchored via a cholesterol-dependent SFK-regulatable linkage between
      a transmembrane cluster sensor and the cytoskeleton.

PMID- 17030988
TI  - Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and
      pericyte TIMP-3.
AB  - The endothelial cell (EC)-derived tissue inhibitor of metalloproteinase-2 (TIMP
      2) and pericyte-derived TIMP-3 are shown to coregulate human capillary tube
      stabilization following EC-pericyte interactions through a combined ability to
      block EC tube morphogenesis and regression in three-dimensional collagen
      matrices. EC-pericyte interactions strongly induce TIMP-3 expression by
      pericytes, whereas ECs produce TIMP-2 in EC-pericyte cocultures. Using small
      interfering RNA technology, the suppression of EC TIMP-2 and pericyte TIMP-3
      expression leads to capillary tube regression in these cocultures in a matrix
      metalloproteinase-1 (MMP-1)-, MMP-10-, and ADAM-15 (a disintegrin and
      metalloproteinase-15)-dependent manner. Furthermore, we show that EC tube
      morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP
      2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors
      include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis
      experiments reveal that TIMP-3 requires its proteinase inhibitory function to
      induce tube stabilization. Overall, these data reveal a novel role for both TIMP
      2 and -3 in the pericyte-induced stabilization of newly formed vascular networks
      that are predisposed to undergo regression and reveal specific molecular targets
      of the inhibitors regulating these events.

PMID- 17030989
TI  - Growth and developmental control in the model and pathogenic aspergilli.

PMID- 17030990
TI  - Upstream and downstream regulation of asexual development in Aspergillus
      fumigatus.
AB  - The opportunistic human pathogen Aspergillus fumigatus produces a large quantity
      of asexual spores (conidia), which are the primary agent causing invasive
      aspergillosis in immunocompromised patients. We investigated the mechanisms
      controlling asexual sporulation (conidiation) in A. fumigatus via examining
      functions of four key regulators, GpaA (Galpha), AfFlbA (RGS), AfFluG, and
      AfBrlA, previously studied in Aspergillus nidulans. Expression analyses of gpaA,
      AfflbA, AffluG, AfbrlA, and AfwetA throughout the life cycle of A. fumigatus
      revealed that, while transcripts of AfflbA and AffluG accumulate constantly, the
      latter two downstream developmental regulators are specifically expressed during
      conidiation. Both loss-of-function AfflbA and dominant activating GpaA(Q204L)
      mutations resulted in reduced conidiation with increased hyphal proliferation,
      indicating that GpaA signaling activates vegetative growth while inhibiting
      conidiation. As GpaA is the primary target of AfFlbA, the dominant interfering
      GpaA(G203R) mutation suppressed reduced conidiation caused by loss of AfflbA
      function. These results corroborate the hypothesis that functions of G proteins
      and RGSs are conserved in aspergilli. We then examined functions of the two major
      developmental activators AfFluG and AfBrlA. While deletion of AfbrlA eliminated
      conidiation completely, null mutation of AffluG did not cause severe alterations
      in A. fumigatus sporulation in air-exposed culture, implying that, whereas the
      two aspergilli may have a common key downstream developmental activator, upstream
      mechanisms activating brlA may be distinct. Finally, both AffluG and AfflbA
      mutants showed reduced conidiation and delayed expression of AfbrlA in
      synchronized developmental induction, indicating that these upstream regulators
      contribute to the proper progression of conidiation.

PMID- 17030991
TI  - The intracellular siderophore ferricrocin is involved in iron storage, oxidative
      stress resistance, germination, and sexual development in Aspergillus nidulans.
AB  - Iron is required by most organisms, but an excess of this metal is potentially
      toxic. Consequently, uptake and intracellular storage of iron are tightly
      controlled. The filamentous fungus A. nidulans lacks the iron storage compound
      ferritin but possesses an intracellular siderophore, which is accumulated in a
      highly regulated manner as iron-free desferri-ferricrocin or iron-containing
      ferricrocin via transcriptional regulation of the nonribosomal peptide synthetase
      SidC. Biosynthesis of desferri-ferricrocin was low during iron-replete conditions
      but up-regulated by both iron starvation and intracellular iron excess, the
      latter caused by either a shift from iron-depleted to high-iron conditions or
      deregulation of iron uptake. Consequently, ferricrocin constituted only about 5%
      of the total iron content under iron-replete conditions but up to 64% during
      conditions of intracellular excess. In contrast, during iron starvation, desferri
      ferricrocin was accumulated, which appears to represent a proactive strategy to
      prevent iron toxicity. Accumulation of the intracellular siderophore was also up
      regulated by oxidative stress, which underscores the intertwining of iron
      metabolism and oxidative stress. Lack of the intracellular siderophore causes
      pleiotropic effects, as SidC deficiency results in (i) less-efficient utilization
      of iron, indicated by reduced growth under iron-depleted conditions and a higher
      iron demand under iron-replete conditions, (ii) delayed germination under iron
      depleted conditions, (iii) increased sensitivity of conidia to oxidative stress,
      and (iv) elimination of cleistothecia formation in homothallic conditions.

PMID- 17030992
TI  - Function of Candida albicans adhesin Hwp1 in biofilm formation.
AB  - Hwp1 is a well-characterized Candida albicans cell surface protein, expressed
      only on hyphae, that mediates tight binding to oral epithelial cells. Prior
      studies indicate that HWP1 expression is dependent upon Bcr1, a key regulator of
      biofilm formation. Here we test the hypothesis that Hwp1 is required for biofilm
      formation. In an in vitro model, the hwp1/hwp1 mutant produces a thin biofilm
      that lacks much of the hyphal mass found in the hwp1/HWP1 reconstituted strain.
      In a biofilm cell retention assay, we find that the hwp1/hwp1 mutant is defective
      in retention of nonadherent bcr1/bcr1 mutant cells. In an in vivo rat venous
      catheter model, the hwp1/hwp1 mutant has a severe biofilm defect, yielding only
      yeast microcolonies in the catheter lumen. These properties of the hwp1/hwp1
      mutant are consistent with its role as a hypha-specific adhesin and indicate that
      it is required for normal biofilm formation. Overexpression of HWP1 in a
      bcr1/bcr1 mutant background improves adherence in the in vivo catheter model.
      This finding provides additional support for the model that Hwp1 is critical for
      biofilm adhesion. Hwp1 is the first cell surface protein known to be required for
      C. albicans biofilm formation in vivo and is thus an excellent therapeutic
      target.

PMID- 17030993
TI  - Gis4, a new component of the ion homeostasis system in the yeast Saccharomyces
      cerevisiae.
AB  - Gis4 is a new component of the system required for acquisition of salt tolerance
      in Saccharomyces cerevisiae. The gis4Delta mutant is sensitive to Na(+) and Li(+)
      ions but not to osmotic stress. Genetic evidence suggests that Gis4 mediates its
      function in salt tolerance, at least partly, together with the Snf1 protein
      kinase and in parallel with the calcineurin protein phosphatase. When exposed to
      salt stress, mutants lacking gis4Delta display a defect in maintaining low
      intracellular levels of Na(+) and Li(+) ions and exporting those ions from the
      cell. This defect is due to diminished expression of the ENA1 gene, which encodes
      the Na(+) and Li(+) export pump. The protein sequence of Gis4 is poorly conserved
      and does not reveal any hints to its molecular function. Gis4 is enriched at the
      cell surface, probably due to C-terminal farnesylation. The CAAX box at the C
      terminus is required for cell surface localization but does not seem to be
      strictly essential for the function of Gis4 in salt tolerance. Gis4 and Snf1 seem
      to share functions in the control of ion homeostasis and ENA1 expression but not
      in glucose derepression, the best known role of Snf1. Together with additional
      evidence that links Gis4 genetically and physically to Snf1, it appears that Gis4
      may function in a pathway in which Snf1 plays a specific role in controlling ion
      homeostasis. Hence, it appears that the conserved Snf1 kinase plays roles in
      different pathways controlling nutrient as well as stress response.

PMID- 17030994
TI  - Identification of PhIL1, a novel cytoskeletal protein of the Toxoplasma gondii
      pellicle, through photosensitized labeling with 5-[125I]iodonaphthalene-1-azide.
AB  - The pellicle of the protozoan parasite Toxoplasma gondii is a unique triple
      bilayer structure, consisting of the plasma membrane and two tightly apposed
      membranes of the underlying inner membrane complex. Integral membrane proteins of
      the pellicle are likely to play critical roles in host cell recognition,
      attachment, and invasion, but few such proteins have been identified. This is in
      large part because the parasite surface is dominated by a family of abundant and
      highly immunogenic glycosylphosphatidylinositol (GPI)-anchored proteins, which
      has made the identification of non-GPI-linked proteins difficult. To identify
      such proteins, we have developed a radiolabeling approach using the hydrophobic,
      photoactivatable compound 5-[(125)I]iodonaphthalene-1-azide (INA). INA can be
      activated by photosensitizing fluorochromes; by restricting these fluorochromes
      to the pellicle, [(125)I]INA labeling will selectively target non-GPI-anchored
      membrane-embedded proteins of the pellicle. We demonstrate here that three known
      membrane proteins of the pellicle can indeed be labeled by photosensitization
      with INA. In addition, this approach has identified a novel 22-kDa protein, named
      PhIL1 (photosensitized INA-labeled protein 1), with unexpected properties. While
      the INA labeling of PhIL1 is consistent with an integral membrane protein, the
      protein has neither a transmembrane domain nor predicted sites of lipid
      modification. PhIL1 is conserved in apicomplexan parasites and localizes to the
      parasite periphery, concentrated at the apical end just basal to the conoid.
      Detergent extraction and immunolocalization data suggest that PhIL1 associates
      with the parasite cytoskeleton.

PMID- 17030995
TI  - Transcriptome analysis of Aspergillus nidulans exposed to camptothecin-induced
      DNA damage.
AB  - We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes
      from this fungus to monitor gene expression of both wild-type and uvsB(ATR) (the
      homologue of the ATR gene) deletion mutant strains in a time course exposure to
      camptothecin (CPT). The results revealed a total of 1,512 and 1,700 genes in the
      wild-type and uvsB(ATR) deletion mutant strains that displayed a statistically
      significant difference at at least one experimental time point. We characterized
      six genes that have increased mRNA expression in the presence of CPT in the wild
      type strain relative to the uvsB(ATR) mutant strain: fhdA (encoding a forkhead
      associated domain protein), tprA (encoding a hypothetical protein that contains a
      tetratrico peptide repeat), mshA (encoding a MutS homologue involved in mismatch
      repair), phbA (encoding a prohibitin homologue), uvsC(RAD51) (the homologue of
      the RAD51 gene), and cshA (encoding a homologue of the excision repair protein
      ERCC-6 [Cockayne's syndrome protein]). The induced transcript levels of these
      genes in the presence of CPT require uvsB(ATR). These genes were deleted, and
      surprisingly, only the DeltauvsC mutant strain was sensitive to CPT; however, the
      others displayed sensitivity to a range of DNA-damaging and oxidative stress
      agents. These results indicate that the selected genes when inactivated display
      very complex and heterogeneous sensitivity behavior during growth in the presence
      of agents that directly or indirectly cause DNA damage. Moreover, with the
      exception of UvsC, deletion of each of these genes partially suppressed the
      sensitivity of the DeltauvsB strain to menadione and paraquat. Our results
      provide the first insight into the overall complexity of the response to DNA
      damage in filamentous fungi and suggest that multiple pathways may act in
      parallel to mediate DNA repair.

PMID- 17030996
TI  - Molecular studies reveal frequent misidentification of Aspergillus fumigatus by
      morphotyping.
AB  - Aspergillus fumigatus has been understood to be the most common cause of invasive
      aspergillosis (IA) in all epidemiological surveys. However, recent studies have
      uncovered a large degree of genetic heterogeneity between isolates
      morphologically identified as A. fumigatus, leading to the description of a new
      species, Aspergillus lentulus. Here, we examined the genetic diversity of
      clinical isolates identified as A. fumigatus using restriction enzyme
      polymorphism analysis and sequence-based identification. Analysis of 50 clinical
      isolates from geographically diverse locations recorded the presence of at least
      three distinct species: A. lentulus, Aspergillus udagawae, and A. fumigatus. In
      vitro, A. lentulus isolates demonstrated decreased susceptibility to antifungal
      drugs currently used for IA, including amphotericin B, voriconazole, and
      caspofungin; A. udagawae isolates demonstrated decreased in vitro susceptibility
      to amphotericin B. Results of the present study demonstrate that current
      phenotypic methods to identify fungi do not differentiate between genetically
      distinct species in the A. fumigatus group. Differential antifungal
      susceptibilities of these species may account for some of the reported poor
      outcomes of therapy in clinical studies.

PMID- 17030997
TI  - Modulation of Leishmania ABC protein gene expression through life stages and
      among drug-resistant parasites.
AB  - The ATP-binding cassette (ABC) protein superfamily is one of the largest
      evolutionarily conserved families and is found in all kingdoms of life. The
      recent completion of the Leishmania genome sequence allowed us to analyze and
      classify its encoded ABC proteins. The complete sequence predicts a data set of
      42 open reading frames (ORFs) coding for proteins belonging to the ABC
      superfamily, with representative members of every major subfamily (from ABCA to
      ABCH) commonly found in eukaryotes. Comparative analysis showed that the same ABC
      data set is found between Leishmania major and Leishmania infantum and that some
      orthologues are found in the genome of the related parasites Trypanosoma brucei
      and Trypanosoma cruzi. Customized DNA microarrays were made to assess ABC gene
      expression profiling throughout the two main Leishmania life stages. Two ABC
      genes (ABCA3 and ABCG3) are preferentially expressed in the amastigote stage,
      whereas one ABC gene (ABCF3) is more abundantly expressed in promastigotes.
      Microarray-based expression profiling experiments also revealed that three ABC
      genes (ABCA3, ABCC3, and ABCH1) are overexpressed in two independent antimony
      resistant strains compared to the parental sensitive strain. All microarray
      results were confirmed by real-time reverse transcription-PCR assays. The present
      study provides a thorough phylogenic classification of the Leishmania ABC
      proteins and sets the basis for further functional studies on this important
      class of proteins.

PMID- 17030998
TI  - A glucose sensor in Candida albicans.
AB  - The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and
      Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by
      regulating the expression of genes encoding hexose transporters. We found that
      HGT4 is required for glucose induction of the expression of HGT12, HXT10, and
      HGT7, which encode apparent hexose transporters in C. albicans. An hgt4Delta
      mutant is defective for growth on fermentable sugars, which is consistent with
      the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be
      sensitive to glucose levels similar to those in human serum ( approximately 5
      mM). HGT4 expression is repressed by high levels of glucose, which is consistent
      with the idea that it encodes a high-affinity sugar sensor. Glucose sensing
      through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans
      cells: hgt4Delta mutants are hypofilamented, and a constitutively signaling form
      of Hgt4 confers hyperfilamentation of cells. The hgt4Delta mutant is less
      virulent than wild-type cells in a mouse model of disseminated candidiasis. These
      results suggest that Hgt4 is a high-affinity glucose sensor that contributes to
      the virulence of C. albicans.

PMID- 17030999
TI  - SWI/SNF displaces SAGA-acetylated nucleosomes.
AB  - SWI/SNF is a well-characterized chromatin remodeling complex that remodels
      chromatin by sliding nucleosomes in cis and/or displacing nucleosomes in trans.
      The latter mechanism has the potential to remove promoter nucleosomes, allowing
      access to transcription factors and RNA polymerase. In vivo, histone acetylation
      often precedes apparent nucleosome loss; therefore, we sought to determine
      whether nucleosomes containing acetylated histones could be displaced by the
      SWI/SNF chromatin remodeling complex. We found that SAGA-acetylated histones were
      lost from an immobilized nucleosome array when treated with the SWI/SNF complex.
      When the nucleosome array was acetylated by SAGA in the presence of bound
      transcription activators, it generated a peak of acetylation surrounding the
      activator binding sites. Subsequent SWI/SNF treatment suppressed this acetylation
      peak. Immunoblots indicated that SWI/SNF preferentially displaced acetylated
      histones from the array relative to total histones. Moreover, the Swi2/Snf2
      bromodomain, an acetyl-lysine binding domain, played a role in the displacement
      of acetylated histones. These data indicate that targeted histone acetylation by
      the SAGA complex predisposes promoter nucleosomes for displacement by the SWI/SNF
      complex.

PMID- 17031000
TI  - Cooperation between reverse transcriptase and integrase during reverse
      transcription and formation of the preintegrative complex of Ty1.
AB  - Reverse transcriptase (RT) and integrase (IN) play a central role in the
      replication and transposition of retroelements. Increasing evidence suggests that
      the interaction between these two enzymes is functional and plays an important
      role in replication. In the yeast Saccharomyces cerevisiae retrotransposon Ty1,
      the interaction of IN with RT is critical for the formation of an active
      conformation of RT. We show here that the RT associated with VLPs is active only
      if it is in close interaction with IN. To probe the IN-RT cis-trans relationship,
      we have used a complementation assay based on coexpressing two transposons. We
      show that IN acts in cis to activate RT and that a functional integrase provided
      in trans is not able to complement replication and transposition defects of IN
      deletion or IN active-site mutant elements. Our data support a model in which IN
      not only interacts closely with RT during reverse transcription but also remains
      associated with RT during the formation of the preintegrative complex.

PMID- 17031001
TI  - Function of the Dictyostelium discoideum Atg1 kinase during autophagy and
      development.
AB  - When starved, the amoebae of Dictyostelium discoideum initiate a developmental
      process that results in the formation of fruiting bodies in which stalks support
      balls of spores. The nutrients and energy necessary for development are provided
      by autophagy. Atg1 is a protein kinase that regulates the induction of autophagy
      in the budding yeast Saccharomyces cerevisiae. In addition to a conserved kinase
      domain, Dictyostelium Atg1 has a C-terminal region that has significant homology
      to the Caenorhabditis elegans and mammalian Atg1 homologues but not to the
      budding yeast Atg1. We investigated the function of the kinase and conserved C
      terminal domains of D. discoideum Atg1 (DdAtg1) and showed that these domains are
      essential for autophagy and development. Kinase-negative DdAtg1 acts in a
      dominant-negative fashion, resulting in a mutant phenotype when expressed in the
      wild-type cells. Green fluorescent protein-tagged kinase-negative DdAtg1
      colocalizes with red fluorescent protein (RFP)-tagged DdAtg8, a marker of
      preautophagosomal structures and autophagosomes. The conserved C-terminal region
      is essential for localization of kinase-negative DdAtg1 to autophagosomes labeled
      with RFP-tagged Dictyostelium Atg8. The dominant-negative effect of the kinase
      defective mutant also depends on the C-terminal domain. In cells expressing
      dominant-negative DdAtg1, autophagosomes are formed and accumulate but seem not
      to be functional. By using a temperature-sensitive DdAtg1, we showed that DdAtg1
      is required throughout development; development halts when the cells are shifted
      to the restrictive temperature, but resumes when cells are returned to the
      permissive temperature.

PMID- 17031003
TI  - A putative Ariadne-like ubiquitin ligase is required for Dictyostelium discoideum
      development.
AB  - The Dictyostelium rbrA gene encodes a putative Ariadne ubiquitin ligase. rbrA(-)
      cells form defective slugs that cannot phototax. Prestalk cell numbers are
      reduced in rbrA(-) slugs, and these prestalk cells do not localize to the tip of
      slugs. Chimeric slugs containing wild-type cells could phototax and form fruiting
      bodies.

PMID- 17031002
TI  - Role of the Fusarium fujikuroi TOR kinase in nitrogen regulation and secondary
      metabolism.
AB  - In Fusarium fujikuroi, the biosynthesis of gibberellins (GAs) and bikaverin is
      under control of AreA-mediated nitrogen metabolite repression. Thus far, the
      signaling components acting upstream of AreA and regulating its nuclear
      translocation are unknown. In Saccharomyces cerevisiae, the target of rapamycin
      (TOR) proteins, Tor1p and Tor2p, are key players of nutrient-mediated signal
      transduction to control cell growth. In filamentous fungi, probably only one TOR
      kinase-encoding gene exists. However, nothing is known about its function.
      Therefore, we investigated the role of TOR in the GA-producing fungus F.
      fujikuroi in order to determine whether TOR plays a role in nitrogen regulation,
      especially in the regulation of GA and bikaverin biosynthesis. We cloned and
      characterized the F. fujikuroi tor gene. However, we were not able to create
      knockout mutants, suggesting that TOR is essential for viability. Inhibition of
      TOR by rapamycin affected the expression of AreA-controlled secondary metabolite
      genes for GA and bikaverin biosynthesis, as well as genes involved in
      transcriptional and translational regulation, ribosome biogenesis, and autophagy.
      Deletion of fpr1 encoding the FKBP12-homologue confirmed that the effects of
      rapamycin are due to the specific inhibition of TOR. Interestingly, the
      expression of most of the TOR target genes has been previously shown to be also
      affected in the glutamine synthetase mutant, although in the opposite way. We
      demonstrate here for the first time in a filamentous fungus that the TOR kinase
      is involved in nitrogen regulation of secondary metabolism and that rapamycin
      affects also the expression of genes involved in translation control, ribosome
      biogenesis, carbon metabolism, and autophagy.

PMID- 17031004
TI  - N-acetylcysteine partially reverses oxidative stress and apoptosis exacerbated by
      Mg-deficiency culturing conditions in primary cultures of rat and human
      hepatocytes.
AB  - OBJECTIVE: The effects of magnesium (Mg) deficiency on the rate of oxidative
      stress and apoptosis in primary cultures of human hepatocytes were compared to
      cultured rat hepatocytes. The possible reversion by N-acetylcysteine (NAC) in Mg
      deficient culturing conditions was evaluated. METHODS: Incubations were conducted
      for up to 72 h in media containing a deficient (0-0.4 mM) or a physiological (0.8
      mM) Mg concentration, and in the presence or absence of NAC after 24 h of culture
      in these Mg concentration conditions. RESULTS: We obtained similar profiles in
      terms of apoptosis and oxidative stress in primary cultures of human hepatocytes,
      as compared to rat hepatocytes, i.e. a Mg concentration-dependent effect on the
      caspase-3 activity and GSH levels after 72 h of culture, caspase-3 activity being
      highest and GSH levels being lowest in Mg-free cultures. The addition of NAC to
      culture media after the first 24 h of culture increased GSH concentrations. This
      was accompanied in Mg-deficient cultures by a decrease in both the caspase-3
      activity and the lipid peroxidation. However, when culturing hepatocytes with
      physiological Mg concentrations, an increase in both caspase-3 activity and lipid
      peroxidation was observed. CONCLUSIONS: Our results indicate that Mg deficiency
      exacerbates the rate of apoptosis in cultured hepatocytes, associated with an
      increase in oxidative stress, the sensitivity of human hepatocytes being
      equivalent to that of rat hepatocytes. They also indicate a dual role of NAC
      and/or GSH, i.e. protective for hepatocytes placed in a Mg-deficient environment,
      while deleterious for hepatocytes placed in a Mg-physiological environment.

PMID- 17031005
TI  - Dietary fiber intake: assessing the degree of agreement between food frequency
      questionnaires and 4-day food records.
AB  - OBJECTIVE: To assess the degree of agreement (comparability) between dietary
      fiber intakes reported on a food frequency questionnaire (FFQ) with 4-day food
      records (4DFR) and determine whether demographic, behavioral and biological
      factors influence comparability. METHODS: At baseline and year one, all
      participants in the Polyp Prevention Trial (PPT), a multi-center randomized,
      clinical trial of a low-fat, high fiber, high fruit/vegetable eating plan and
      recurrence of large bowel adenomatous polyps were instructed in dietary
      assessment and completed a 106-item FFQ and 4DFR that trained nutritionists
      reviewed. A random sub-cohort of participants (n = 399) was selected from the
      intervention and control arms of the PPT for analysis of both FFQ and 4DFR.
      RESULTS: Baseline crude and energy-adjusted fiber intakes were significantly
      higher in the 4DFR than the FFQ (P = 0.001). Using Bland-Altman statistics, the
      mean difference (FFQ-4DFR) was -0.11 g/MJ; while the limits of agreement were 
      1.45, 1.23 g/MJ. The mean fiber difference increased with increasing average
      intake (FFQ + 4DFR)/2, (P = 0.004) for men, but not women (P = 0.10), suggesting
      that fiber intake was under-estimated in the FFQ, relative to the 4-DFR, for men
      with low fiber intakes and over-estimated for men with high intakes. Smoking and
      gender significantly influenced the average intake at baseline, whereas other
      demographic and behavioral factors did not. Education was significantly
      associated with average difference in fiber intake at baseline, but not at year
      1. CONCLUSIONS: This study of clinical trial volunteers revealed differences in
      the ability to comparably report fiber intake across tools by gender, smoking,
      and education, however participants' repeated training in dietary assessment
      improved comparability in reporting over time.

PMID- 17031006
TI  - Food cravings, ethnicity and other factors related to eating out.
AB  - OBJECTIVE: Our objective was to study factors related to eating patterns,
      specifically whether certain food cravings were associated with frequency of
      meals eaten away from home. METHODS: Data were collected from 277 patients from a
      family medicine residency office in Arizona. The survey questionnaire included
      information about the respondents' demographics, socioeconomic status, food
      cravings, as well as, number of meals eaten away from home. The food craving
      inventory included foods in four categories identified by factor analysis: fast
      foods, carbohydrates, sweets and snacks. Data on food cravings were factor
      analyzed and scale scores were derived. RESULTS: Being a Hispanic adult, working
      outside the home, and cravings for individual food items were related to eating
      more meals away from home. If the mother was working outside the home, the
      youngest child ate an average of two additional meals away from home each week.
      In general respondent's cravings for some specific food items were also related
      to higher numbers of meals their child ate away from home. Cravings for both fast
      food and snacks were positively correlated with adult eating out. None of the
      respondents' scale scores were related to child's eating away from home. Adults
      with Arizona Health Care Cost Containment System insurance (AHCCCS--a form of
      Medicaid) and older adults were less likely to eat away from home compared to
      patients with other types of insurance. CONCLUSIONS: Socioeconomic status,
      ethnicity, and food cravings are related to adult and child patterns of eating
      meals away from home.

PMID- 17031007
TI  - Evaluating efficacy of a chitosan product using a double-blinded, placebo
      controlled protocol.
AB  - OBJECTIVE: To examine the safety and efficacy of a chitosan dietary supplement on
      body composition under free-living conditions. DESIGN: In a randomized, double
      blinded, placebo-controlled dietary intervention protocol, subjects were assigned
      to a treatment group (TRT), a placebo group (PLA) and a control group (CTL).
      SUBJECTS: A total of 150 overweight adults enrolled; 134 (89.3%) completed the
      study; 111 (82.8%) were women who were similarly distributed in the three groups.
      INTERVENTION: The TRT group took six 500 mg chitosan capsules per day and both
      TRT and PLA groups wore pedometers during their waking hours and recorded daily
      step totals. The CTL group followed weight loss programs of their choice, and
      took the same baseline and ending tests. MEASURES OF OUTCOME: Outcome measures
      were Dual Energy X-ray Absorptiometry tests, fasting blood chemistries, and self
      reported daily activity levels and caloric intakes. RESULTS: Compared to CTL, the
      TRT group lost more weight (-2.8 lbs vs. +0.8 lbs, p < 0.001) and fat mass (-2.6
      lbs vs. +0.1 lbs, p = 0.006). Compared to PLA, the TRT group lost more weight (
      2.8 lbs. vs. -0.6 lbs, p = 0.03), % fat (-0.8% vs. +0.4%, p = 0.003), fat mass (
      2.6 lbs vs. +0.6 lbs, p = 0.001) and had a greater body composition improvement
      index (BCI) (+2.4 lbs vs. -1.9 lbs, p = 0.002). CONCLUSIONS: These data provide
      evidence for the efficacy of a chitosan compound to facilitate the depletion of
      excess body fat under free-living conditions with minimal loss of fat-free or
      lean body mass.

PMID- 17031008
TI  - Vitamin D status in a rural postmenopausal female population.
AB  - BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as
      common in North American and European populations, but the extent of the
      shortfall and the parameters of the distribution for populations of interest
      remain uncertain. PURPOSE: To report the distribution of values for serum 25
      hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women,
      together with quantification of factors related to vitamin D status. SETTING:
      Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N).
      PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older
      recruited into a four-year trial of calcium and vitamin D supplementation.
      METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained
      on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied
      cyclically with season, with the solar cycle explaining 2.9% of the total
      variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1
      nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear
      relationship with serum parathyroid hormone (PTH), with the inflection point of
      the curve located at approximately 80 nmol/L. Supplements containing vitamin D
      were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless,
      approximately 4% of all women had values below the laboratory reference range and
      more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D
      concentration was positively correlated with the size of daily vitamin D
      supplement dose, and negatively with age, weight, and body mass index (P < 0.01
      for all). In stepwise multiple linear regression models, weight, age, and
      supplement dose were independently correlated with seasonally adjusted serum
      25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D
      concentration. Women taking supplements had only one-sixth the chance of having a
      25(OH)D value below the reference limit of the assay, compared to women who did
      not use supplements. CONCLUSIONS: Approximately two-thirds of this rural
      population fell below 80 nmol/L, a value considered to be the lower end of the
      optimal range. Based on the slope of 25(OH)D on supplement dose observed in these
      women, it would require an additional vitamin D input of nearly 2000 IU/d to
      reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to
      levels of 80 nmol/L or higher.

PMID- 17031009
TI  - Screening performances of the International Obesity Task Force body mass index
      cut-off values in adolescents.
AB  - OBJECTIVE: To try to improve the International Obesity Task Force (IOTF) BMI cut
      off values, in terms of prediction of body fat percentage assessed by dual-energy
      X-ray absorptiometry (DXA), in adolescents. METHODS: Cross-sectional survey of
      the adolescents from the city of Zaragoza (Spain). For this analysis we have
      included 286 adolescents (116 boys and 170 girls) aged 13.0-17.9 years. Body mass
      index (BMI) was calculated as body weight (kg), divided by height (m) squared.
      The percentage of body fat (BF%) was estimated by the use of DXA. RESULTS: We
      have calculated, new BMI cut-off values (AVENA cut-offs) to predict BF%, for boys
      and girls in each age group. In male adolescents, sensitivity was higher with the
      IOTF cut-offs (0.71, 95th C.I.: 0.44, 0.90) than with the AVENA ones (0.53, 95th
      C.I.: 0.28, 0.77), and specificity was very similar with both cut-off values
      (0.86 and 0.88, respectively), the differences being not statistically
      significant. In girls, both sensitivities (0.75 and 0.79, respectively) and
      specificities (0.90 and 0.92, respectively) were very similar with both cut-off
      values, and the differences, not significant. CONCLUSIONS: Optimization of the
      IOTF BMI cut-off values, in terms of BF%, seems not to be possible in
      adolescents. The IOTF criteria should be used only for overweight and obesity
      screening; however, in clinical settings, a more accurate measure of body fat
      should be recommended.

PMID- 17031010
TI  - Effect of a viscous fiber bar on postprandial glycemia in subjects with type 2
      diabetes.
AB  - OBJECTIVE: To compare the effect of an experimental viscous fiber (VF) crispy bar
      on the postprandial glucose, insulin, and C-peptide response in adult subjects
      with type 2 diabetes to two commercially available control crispy bars. DESIGN:
      The study was a randomized, double-blinded, three period, crossover study.
      SETTING: The study was conducted at two sites: Park Nicollet Institute,
      International Diabetes Center, Minneapolis, MN, and Radiant Research, Inc.,
      Minneapolis, MN. SUBJECTS: A total of 60 adults with type 2 diabetes taking oral
      antihyperglycemic medication participated in the study. INTERVENTION: After an
      overnight fast, subjects consumed a test meal containing an equicaloric amount
      (300 kcal) of an experimental VF crispy bar or one of two commercially available
      crispy bars at each of three test visits, followed by a four hour meal tolerance
      test. Subjects also completed gastrointestinal (GI) response records for the 24
      hours following each test visit. RESULTS: The VF crispy bars produced
      significantly lower glucose (p < 0.0001), insulin (p < 0.0001), and C-peptide (p
      < 0.0001) responses (as measured by positive area under the curve) in subjects
      with type 2 diabetes, as compared with the two commercially available bars.
      Intensity (p < 0.05) and frequency (p < 0.05) of flatulence were significantly
      higher with the VF bar as compared with the 2 commercial bars. While the VF bar
      produced significant subjective GI tolerance scoring values, the mean value was
      below 3 on a scale of 0 (no effect) to 10 (most severe effect) for all tested
      materials. CONCLUSIONS: The incorporation of VF into a crispy bar provided a
      means to improve blood glucose levels by reducing postprandial glucose, insulin,
      and C-peptide responses in subjects with type 2 diabetes. Though associated with
      some GI symptoms, VF may have application in improving the postprandial glycemic
      response in people with diabetes attempting intensive glucose control.

PMID- 17031011
TI  - Safety and tolerance of a probiotic formula in early infancy comparing two
      probiotic agents: a pilot study.
AB  - OBJECTIVE: To compare the safety and tolerance of two formulas, supplemented with
      different probiotic agents, in early infancy. DESIGN: Prospective randomized
      placebo-controlled trial. SETTING: Clinics of a University Medical Center.
      SUBJECTS: Full-term healthy infants aged less than 4 months. INTERVENTION:
      Infants were randomly assigned for 4 weeks to a standard milk-based formula
      supplemented with either Bifidobacterium lactis (BB-12), Lactobacillus reuteri
      (ATCC 55730) or a probiotics-free formula. MEASURES OF OUTCOME: Growth
      parameters, daily characteristics of feeding, stooling and behavior, and side
      effects. RESULTS: Fifty-nine infants, aged 3-65 days, were included. Subjects in
      all three groups were similar at entry in terms of gestational age, birth weight,
      sex, growth parameters and breast feeding rate prior to the study. The
      supplemented formulas were well accepted and did not reveal any adverse effects.
      A comparison of growth parameters, and variables of feeding, stooling and crying
      and irritability did not reveal any significant differences between groups.
      CONCLUSIONS: The use of formula supplemented with either Lactobacillus reuteri or
      Bifidobacterium lactis in early infancy, was safe, well tolerated and did not
      adversely affect growth, stooling habits or infant behavior.

PMID- 17031012
TI  - Alpha-tocopherol distribution in lipoproteins and anti-inflammatory effects
      differ between CHD-patients and healthy subjects.
AB  - OBJECTIVE: The purpose of this study was to investigate the dose-dependent
      effects of RRR-alpha-tocopherol supplementation in coronary heart disease (CHD)
      patients and healthy subjects on plasma alpha-tocopherol levels, plasma
      lipoprotein distribution, LDL oxidation, and inflammatory plasma markers.
      METHODS: 12 patients with coronary heart disease and 12 healthy subjects were
      supplemented with increasing dosages of RRR-alpha-tocopherol at 100, 200 and 400
      mg/day for a period of 3 weeks per dose. Lipoproteins were separated by FPLC and
      ultracentrifugation. Alpha-tocopherol was measured by HPLC. Resistance of LDL to
      oxidation was determined by reading the absorption at 234 nm after CuCl2-induced
      oxidation. Clinical chemistry and inflammatory markers were measured on automated
      analysis systems. RESULTS: Plasma alpha-tocopherol concentrations at baseline
      were comparable between CHD-patients and healthy subjects (21.7 +/- 4.7
      micromol/L and 25.8 +/- 7.6 micromol/L, respectively). CHD-patients showed a
      significant increase (59%) of plasma alpha-tocopherol concentrations to 34.6 +/-
      9.8 micromol/L at a dosage of 100 mg/day RRR-alpha-tocopherol, whereas healthy
      subjects showed a significant (54%) increase to 39.7 +/- 6.1 micromol/L only with
      400 mg/day RRR-alpha-tocopherol. In addition, CHD-patients showed a significantly
      increased enrichment of alpha-tocopherol in VLDL. Supplementation (200 mg/day)
      caused a significant decrease of the acute phase plasma proteins C-reactive
      protein (CRP) (-65%) and fibrinogen (-24%). CONCLUSION: Our data demonstrate that
      CHD-patients require lower dosages of alpha-tocopherol supplementation than
      healthy subjects to exert biological effects on plasma lipoproteins and acute
      phase response.

PMID- 17031013
TI  - How much vitamin D3 do the elderly need?
AB  - BACKGROUND: Vitamin D insufficiency poses a problem in many parts of the world,
      the elderly being an especially vulnerable group. This insufficiency results from
      an inadequate amount of sunshine and a low dietary intake of vitamin D.
      Typically, insufficiency is accompanied with high intact parathyroid hormone, (S
      iPTH) concentrations. AIMS OF THE STUDY: We studied how serum 25-hydroxy vitamin
      D (S-25-OHD) concentrations respond to different doses of vitamin D3
      supplementation. Secondly to determine the smallest efficient dose to maintain
      serum 25-OHD concentration above the insufficiency level. We also studied which
      dose would be efficient in decreasing S-iPTH concentration in these subjects.
      SUBJECTS AND METHODS: Forty-nine 65- to 85-year-old women participated. The women
      were randomly assigned into one of four groups receiving 0 (placebo), 5, 10 or 20
      microg of vitamin D3 daily for 12 weeks. Fasting morning blood was drawn at the
      beginning of the study, and thereafter every second week. Calciotropic variables
      were assessed from serum and urine samples. RESULTS: The S-25-OHD concentration
      increased significantly (p < 0.001) in all supplemented groups [5 microg: by 10.9
      (8.5) nmol/L, 10 microg: by 14.4 (6.9) nmol/L, 20 microg: by 23.7 (11.9) nmol/L],
      whereas it decreased in the placebo group by 8.3 (13.2) nmol/L. Equilibrium in S
      25-OHD concentration was reached in all groups after 6 weeks of supplementation
      at 57.7 (8.9) nmol/L, 59.9 (8.9) nmol/L and 70.9 (8.9) nmol/L in the groups with
      increasing vitamin D supplementation. The dose-response to supplementation
      decreased with increasing vitamin D status at baseline, r = -0.513, p = 0.002. S
      iPTH tended to decrease in those with highest dose response to supplementation.
      CONCLUSIONS: A clear dose response was noted in S-25-OHD to different doses of
      vitamin D3. The recommended dietary intake of 15 microg is adequate to maintain
      the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal
      S-25-OHD is higher than that even higher vitamin D intakes are needed.
      Interestingly, subjects with lower vitamin D status at baseline responded more
      efficiently to supplementation than those with more adequate status.

PMID- 17031014
TI  - Metabolic advantage of low-carbohydrate diets.

PMID- 17031015
TI  - Carbohydrate intake, serum lipids, and evolution.

PMID- 17031017
TI  - Geographic variation in alcohol, drug, and mental health services utilization:
      what are the sources of the variation?
AB  - BACKGROUND: Studies have documented geographic variation in health services
      utilization over a range of medical, surgical, and psychiatric conditions. These
      geographic differences are of concern to policy makers, as they may represent
      either excessive levels of unnecessary care or inappropriately low utilization of
      necessary services. However, the sources of geographic variation are not well
      understood, and variation may not represent a quality problem, to the extent that
      geographic variation is due to sampling variability or variation in case-mix
      across sites. AIMS OF THE STUDY: Our aim was to determine the extent to which
      geographic variation in assessment and treatment rates for alcohol, drug, and
      mental disorders (ADM) was due to variation in case-mix across sites and to
      quantify the amount of geographic variation after case-mix adjustment. METHODS:
      We analyzed data from Healthcare for Communities, a nationally representative
      telephone survey of ADM disorders and treatment. We utilized fixed effects and
      random intercept models to analyze whether individuals received a brief primary
      care ADM assessment, any primary care ADM treatment, any specialty ADM treatment,
      or any ADM treatment. Using the coefficient of variation and intra-class
      correlation (ICC) as summaries, we simulated reference distributions for the
      amount of variability in ADM assessment and treatment rates expected due to
      variation in case mix across 60 geographic areas. We compared this with the
      actual variation among our 60 sites, and the variation that remained after
      adjusting for ADM disorders, physical health, and socioeconomic characteristics.
      RESULTS: The amount of the variation in assessment and treatment rates explained
      by geographic area in unadjusted fixed effects and random intercepts models was
      statistically significant with R2 statistics ranging from 1% to 2% in fixed
      effects models and ICC's ranging from 0.009 to 0.043. Considerably more variation
      was explained in analyses that included individual level characteristics such as
      ADM disorders, physical health, and socioeconomic status, with R2 statistics from
      10% to 19%. In random intercept models the ICC's were decreased 20 to 100% in
      models that adjusted for ADM disorders, physical health, and socioeconomic
      status. DISCUSSION: We found significant variation in ADM assessment and
      treatment rates across geographic sites. However, the magnitude of geographic
      variation was relatively modest, with 0.9 to 4.3% of the total variation in ADM
      assessment and treatment occurring at the geographic level. Further, it appears
      that a moderate amount of this geographic variation may be due to differences in
      case mix across sites. IMPLICATIONS FOR HEALTH POLICY: Although geographic
      variation in assessment and treatment rates can signal variable quality, there
      may be only modest potential for improving quality by reducing geographic
      variation. Further, the success of efforts to decrease geographic variation by
      focusing on provider behavior may be limited by the extent to which systematic
      variation is explained by individual characteristics. IMPLICATIONS FOR FURTHER
      RESEARCH: Future work on geographic differences in mental health care as well as
      in health services more generally should pay particular attention to adjusting
      for individual differences in morbidity, which strongly predict treatment
      utilization.

PMID- 17031018
TI  - Trends in the professional mix and cost of outpatient mental health care.
AB  - BACKGROUND: In recent years, lower cost non-physician providers have been
      increasingly used to deliver outpatient mental health services. METHODS: We
      compared 1997 and 2004 data on outpatient services provided by the Veterans
      Health Administration to examine trends in outpatient provider mix and to
      evaluate the association of outpatient provider mix with average per capita
      outpatient mental health costs. RESULTS: We found a small decline in the
      proportion of outpatient mental health services provided by psychiatrists and an
      increase in the proportion of such services provided by nurses. However, greater
      use of non-physician providers, at the facility level, was associated with
      greater, rather than lower per capita outpatient costs and there was no
      significant change over time. CONCLUSION: While an increasing proportion of
      outpatient mental health visits were with non-psychiatrists, there was not an
      associated decline in per capita mental health costs. Increasing VA workloads
      over the past decade have forced increases in psychiatrist panel size,
      substantially increasing physician efficiency. Additional non-physician staff
      have supported the development of psychosocial rehabilitation and crisis
      intervention capacities needed to cope with a 63% decline in inpatient beds and
      thus have most likely been complements of, rather than substitutes for,
      psychiatrists.

PMID- 17031019
TI  - A systematic review of relations between neighborhoods and mental health.
AB  - BACKGROUND: The relationship between neighborhood characteristics and resident
      mental health has been widely investigated in individual studies in recent years,
      but this literature is not adequately reviewed. AIMS OF THE STUDY: To
      systematically review relevant individual research of the relation between
      neighborhoods and adult mental health by identifying and synthesizing all
      relevant studies in this literature. METHODS: We conducted an electronic search
      with PubMed and PsycINFO, and manual reference-checking, resulting in 8,562
      screened studies of which 29 were selected. Studies were included in the main
      synthesis if they (i) were published in English in peer reviewed journals; (ii)
      had relevant definitions and measures of neighborhood characteristics; (iii)
      utilized standardized measures of adult mental health; (iv) controlled for
      individual characteristics; (v) reported quantitative results; and, (vi) studied
      a population in a developed country. We focused on two key areas within this
      literature: the methodologies utilized to study neighborhood effects and
      quantitative results. With regard to the former, we examined five major issues:
      (i) definitions and measures of neighborhoods; (ii) definitions and measures of
      mental health; (iii) controls for individual level characteristics; (iv)
      conceptual models; and (v) analytical models. As for quantitative results, the
      relation was reviewed by types of neighborhood characteristics. We summarized
      general quantitative findings and drew common conclusions across groups of
      studies. RESULTS: 27/29 studies found statistically significant association
      between mental health and at least one measure of neighborhood characteristics,
      after adjusting for individual factors. This association was evident for all
      types of neighborhood features, varying from sociodemographic characteristics to
      physical environment, and from objective to subjective measures. Neighborhood
      effects were weakened when adding individual-level characteristics into the
      regression models, and were generally modest relative to individual effects.
      DISCUSSION AND LIMITATIONS: Although the evidence is highly consistent across
      studies, detailed evaluation of each individual study reveals a complex reality.
      The included studies used various study designs and measures of mental health and
      neighborhoods, making generalization of their relationships less meaningful. It
      is not possible to conclude that studies with weaker controls for individual
      characteristics found stronger association between neighborhoods and mental
      health and vice versa. As only two studies used randomized and controlled trials,
      causal effects must be interpreted with caution. Formal meta-analysis techniques
      cannot be used due to large heterogeneity across the included studies. Efficient
      methods for quantitative analysis remain a great challenge. IMPLICATIONS FOR
      HEALTH POLICY: The current evidence suggests that efforts to improve mental
      health may be limited if only individual-level interventions are implemented. The
      calculation of the costs and benefits of neighborhood-level interventions
      deserves more attention. Moreover, policy makers may want to incorporate mental
      health as a measure for evaluating neighborhood improvement programs.
      IMPLICATIONS FOR FUTURE RESEARCH: There are not enough replicated or comparable
      studies in this literature to make more precise quantitative conclusions of this
      relation. Key aspects of study design and analyses could be improved to better
      understand the true nature of causal relationships. The data resolution of
      neighborhood characteristics needs to better match with the scale of neighborhood
      definition that is hypothesized to affect the residents' mental health. As
      experimental designs are rare in this area, thoughtful use of panel data,
      instrumental variable (IV) techniques, and other non-experimental approaches
      deserves further exploration.

PMID- 17031020
TI  - Coverage for mental health treatment: do the gaps still persist?
AB  - BACKGROUND: Consumers have long faced high out-of-pocket costs for mental health
      and substance abuse treatment in private health insurance plans, the predominant
      form of insurance coverage in the United States. Nominal mental health benefits
      may have improved from the mid-1990s onwards, as many states passed mental health
      parity mandates and other employers voluntarily improved coverage. However, the
      rapid rise of managed behavioral health care organizations (MBHOs) may have
      effectively offset these gains in nominal coverage. AIMS OF THE STUDY: We examine
      how effective mental health benefits, as measured by actual out-of-pocket
      expenses, compares to coverage for non-mental health treatment and how this has
      changed in recent years. METHODS: We used detailed data on health care use and
      expenses from the nationally representative, Medical Expenditure Panel Survey
      (MEPS) to describe the distribution of out-of-pocket expenses for mental health
      and non-mental health ambulatory visits and prescription drug fills and
      demonstrate how this changed between 1996 and 2003. In addition, we use two-limit
      tobit regression models to descriptively examine the factors associated with
      higher out-of-pocket costs for ambulatory mental health treatment. RESULTS: While
      out-of-pockets shares generally decreased over the 1996-2003 period, from 39 to
      35 percent of total expenses for ambulatory mental health visits and from 31 to
      26 percent for non-mental health ambulatory visits, the ratio of out-of-pockets
      costs is still significantly higher for mental health care. Out-of-pocket
      expenses per visit fell as the number of non-mental health visits increased but
      out-of-pocket expenses for mental health visits rose with more visits. Out-of
      pocket expenses for visits to specialty mental health providers were
      substantially higher than for non-psychiatrist physicians. Though prescription
      drug spending increased substantially, the percent paid out-of-pocket did not
      change for mental health and non-mental health related fills. DISCUSSION: Our
      results suggest that expenses for ambulatory mental health visits, especially for
      specialty providers, effectively remain less well covered than other medical
      visits. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Continued high out-of
      pocket expenses for mental health treatment may impede access to mental health
      treatment, especially for those who need greater treatment intensity.
      IMPLICATIONS FOR HEALTH POLICIES: Mental health parity may not ensure that
      coverage for mental health services is, in actuality, equal. IMPLICATIONS FOR
      FURTHER RESEARCH: Additional research is needed in understanding relative changes
      in nominal vs. actual or effective coverage.

PMID- 17031021
TI  - Application of periodic acid-Schiff fluorescence emission for
      immunohistochemistry of living mouse renal glomeruli by an "in vivo
      cryotechnique".
AB  - To identify the distribution of endogenous serum proteins in living mouse renal
      glomeruli under various hemodynamic conditions, we used the periodic acid-Schiff
      (PAS) and its fluorescence emission as a marker for the glomerular basement
      membrane (GBM). The immunostaining for collagen type IV was hardly observed
      without microwave treatment in specimens prepared by an "in vivo cryotechnique".
      However, PAS staining and its fluorescence emission could be clearly visualized
      at the GBM with the "in vivo cryotechnique". Under normotensive conditions,
      immunoreaction products of albumin and immunoglobulin G heavy and light chains
      (IgG(H+L)) were localized within glomerular capillary loops (GCL) but not
      colocalized with the PAS fluorescence emission of the GBM. Under heart-arrest
      conditions and with quick-freezing of resected tissues, albumin, IgG (H+L),
      immunoglobulin kappa light chain, and IgG1 heavy chain (IgG1) were
      immunolocalized within the GCL and mesangial areas, but only albumin and the
      kappa light chain were additionally immunolocalized in Bowman's space, indicating
      their passage through the GBM. Under acute hypertensive conditions, both albumin
      and the kappa light chain, but not IgG1, were clearly immunolocalized along the
      GBM and in the Bowman's space, indicating their increased passage through the
      GBM. The overlapping areas of PAS fluorescence emission and the albumin or kappa
      light chain appeared to be larger with quick-freezing and under the heart arrest
      or acute hypertensive conditions than under normal circulation, whereas those of
      PAS emission and IgG1 did not differ among these conditions. The serum proteins
      passing through the GBM were clearly visualized with the "in vivo cryotechnique",
      immunofluorescence staining, and PAS fluorescence emission.

PMID- 17031022
TI  - In vitro adipocytic conversion in Meckel's chondrocytes in response to a fatty
      acid-containing medium.
AB  - Chick serum (CKS) contains factors that stimulate adipocytes in Meckel's
      chondrocytes in vitro. In the present study, we analyzed levels of fatty acids in
      CKS, and further examined whether these had the potential to convert chondrocytes
      to adipocytes. Phenotypic changes were evaluated by light and electron
      microscopies, bromodeoxyuridine (BrdU) incorporation, triglyceride assays, and
      immunocytochemistry. We showed that CKS contained high levels of fatty acids, and
      a mixed medium containing 5 particular fatty acids inhibited DNA synthesis and
      the proliferation of chondrocytes as it facilitated their differentiation into
      adipocytes. The adipocytes produced were sudan-positive multilocular cells that
      morphologically and histochemically resembled adipocytes induced by the CKS
      containing medium. Almost all lipid droplet-containing cells were positive for
      leptin and alpha-glycerophosphate dehydrogenase (GPDH), as evaluated by
      immunoperoxidase staining, and their triglyceride concentrations markedly
      increased during 4 to 6 days of culture. These results suggested that specific
      fatty acids in CKS are involved in the adipocytic conversion of Meckel's
      chondrocytes.

PMID- 17031023
TI  - Sprouting of sensory neurons in dorsal root ganglia after transection of
      peripheral nerves.
AB  - Morphological reaction of sensory neurons of dorsal root ganglia after peripheral
      nerve transection was investigated by a nerve tracing method using E. coli lacZ
      (beta-galactosidase) gene recombinant adenovirus. The sciatic nerve of the rat
      was transected and inoculated with the gene recombinant adenovirus from the
      cutting end of nerve fibers. The fixation was accomplished from one to six weeks
      after inoculation. A whole mount specimen was observed after the reaction in a X
      galactocidase substrate. Newly formed sprouting processes of dorsal root ganglion
      (DRG) cells appeared, all of them sprouting from the primary segment of DRG
      cells. Developed branches were morphologically categorized in to two types: one
      was the "linear type" which showed diverged branches running straightly along the
      major axis of the DRG; the other was the "winding type" which exhibited a random
      running pattern to the original axons and wound and extended in all directions in
      dorsal root ganglia with many branches. Many of this type encircled other cell
      bodies and formed a ring-like structure. There was no difference in the size of
      cell bodies in either type or between the ring-like structure forming the cells
      and those cells encircled by them.

PMID- 17031024
TI  - The expression and localization of osteopontin in the mouse major salivary
      glands.
AB  - The present study investigated the expression and distribution of osteopontin in
      the mouse major salivary glands. The level of osteopontin expression in the mouse
      submandibular gland was higher (12.7-fold) than that in parotid and sublingual
      glands at the mRNA level. By Western blot analysis, intense positive bands were
      seen at the predicted molecular mass (about 55 kDa) in all the major salivary
      glands, while an approximately 30 kDa band of osteopontin was detected only in
      the submandibular gland. Indirect immunofluorescent and immuno-electron
      microscopy analyses demonstrated the localization of osteopontin in the luminal
      (apical) membranes of acinar cells in all the salivary glands. Osteopontin was
      also localized at the lumen of acini in the submandibular gland. These results
      suggest that the expression of osteopontin in the submandibular gland is
      different from that in the parotid and sublingual glands and that osteopontin may
      be degraded in the mouse submandibular gland.

PMID- 17031025
TI  - The bHLH transcription factors, Hes6 and Mash1, are expressed in distinct subsets
      of cells within adult mouse taste buds.
AB  - Taste buds are multicellular receptor organs embedded in the lingual epithelium
      of vertebrates. Taste cells within these buds are modified epithelial cells as
      they lack axons and turnover rapidly throughout life, yet have neuronal
      properties enabling them to transduce taste stimuli and transmit this information
      to the nervous system. Taste cells are heterogeneous, comprising types I, II, III
      and basal cells, and are continually replaced during adult life, raising the
      question of how these different cells are generated. The molecular mechanisms
      governing taste cell differentiation are unknown, but the Notch signaling system
      has been implicated in this process based upon recent gene expression data. Here
      we investigate the expression in mature taste buds of Notch related transcription
      factors, Hes6 and Mash1, which are among the first genes expressed in embryonic
      taste buds. We further compare these patterns with those of immunocytochemical
      markers of discrete taste cell types. We find that Hes6 is expressed in a subset
      of basally located, possibly progenitor cells, yet is rarely coexpressed with
      taste cell markers. In contrast, Mash1 is detected in some basal cells and in the
      majority of differentiated type III taste cells, but never in type II cells.
      These data suggest a role for Notch signaling in taste cell differentiation in
      adult taste buds.

PMID- 17031026
TI  - High shikimate production from quinate with two enzymatic systems of acetic acid
      bacteria.
AB  - 3-Dehydroshikimate was formed with a yield of 57-77% from quinate via 3
      dehydroquinate by two successive enzyme reactions, quinoprotein quinate
      dehydrogenase (QDH) and 3-dehydroquinate dehydratase, in the cytoplasmic
      membranes of acetic acid bacteria. 3-Dehydroshikimate was then reduced to
      shikimate (SKA) with NADP-dependent SKA dehydrogenase (SKDH) from the same
      organism. When SKDH was coupled with NADP-dependent D-glucose dehydrogenase (GDH)
      in the presence of excess D-glucose as an NADPH re-generating system, SKDH
      continued to produce SKA until 3-dehydroshikimate added initially in the reaction
      mixture was completely converted to SKA. Based on the data presented, a strategy
      for high SKA production was proposed.

PMID- 17031027
TI  - Tumor antigen occurs in N-glycan of royal jelly glycoproteins: honeybee cells
      synthesize T-antigen unit in N-glycan moiety.
AB  - In our previous paper (Kimura, Y., et al., Biosci. Biotechnol. Biochem., 67, 1852
      1856, 2003), we found that a complex type N-glycans containing beta1-3 galactose
      residue occurs on royal jelly glycoproteins. During structural analysis of minor
      components of royal jelly N-glycans, we found complex type N-glycans bearing both
      galactose and N-acetylgalactosamine residues. Detailed structural analysis of
      pyridylaminated oligosaccharide revealed that the newly found N-glycan had a
      complex type structure harboring a tumor marker (T-antigen) unit: Galbeta1
      3GalNAcbeta1-4GlcNAcbeta1-2Manalpha1-6 (Galbeta1-3GalNAcbeta1-4GlcNAcbeta1
      2Manalpha1-3) Manbeta1-4GlcNAcbeta1-4GlcNAc. To our knowledge, this may be the
      first report of the presence of the T-antigen unit in the N-glycan moiety of
      eucaryotic glycoproteins.

PMID- 17031028
TI  - Expression profile of amylolytic genes in Aspergillus nidulans.
AB  - Aspergillus nidulans possessed 16 putative amylolytic genes consisting of 7 alpha
      glucosidase (agdA-F), 7 alpha-amylase (amyA-F), and 2 glucoamylase (glaA and B)
      genes on the genome. Among them, the agdA, agdB, agdE, agdF, amyA, amyB, amyF,
      and glaB genes were induced by isomaltose. AmyR, a Zn(II)(2)Cys(6) transcription
      factor, was required for the induction. The isomaltose-inducible genes possessed
      at least one consensus sequence for AmyR binding, 5'-CGGN(8)CGG, on each promoter
      region. None of the amylolytic genes was induced by maltose. The mRNA levels of
      the amylolytic genes except for agdC, amyD, and amyG increased under carbon
      starved conditions. Release from CreA-dependent carbon catabolite repression was
      the main cause of the increase, but, the mRNA levels of agdB, agdF, amyB, amyF,
      and glaB increased to some extent even in a creA mutant. Therefore, both CreA
      dependent and -independent mechanisms are involved in the up-regulation of the
      amylolytic genes under carbon-starved conditions.

PMID- 17031029
TI  - Sequential regulation of gibberellin, brassinosteroid, and jasmonic acid
      biosynthesis occurs in rice coleoptiles to control the transcript levels of anti
      microbial thionin genes.
AB  - Transcripts of thionin genes encoding antimicrobial peptides were present at a
      high level in rice coleoptiles just after germination, and decreased to an
      undetectable level after about 3 d, but this decline was suppressed by co
      treatment with gibberellic acid (GA(3)) and brassinolide (BL). The temporal
      expression patterns of key enzyme genes for the biosyntheses of gibberellins
      (GAs) and brassinosteroids (BRs) were correlated with the fluctuation of thionin
      mRNAs. Jasmonic acid (JA) replaced the effect of GA3 and BL, and its change in
      endogenous level was parallel to that of the thionin genes. These results
      strongly suggest that thionin gene expression was positively regulated by JA,
      whose endogenous level was synergistically regulated by GAs and BRs. In contrast,
      thionin gene expression in etiolated seedlings remained high while the endogenous
      level of JA was low, suggesting the presence of another signaling pathway in the
      dark to maintain the thionin level.

PMID- 17031030
TI  - A novel labdane-type trialdehyde from myoga (Zingiber mioga Roscoe) that potently
      inhibits human platelet aggregation and human 5-lipoxygenase.
AB  - We screened myoga extracts for inhibitors of human platelet aggregation and human
      5-lipoxygenase. We identified a novel labdane type of diterpene, together with
      three known diterpenes (miogadial and galanals A and B) from the flower buds of
      myoga. Spectroscopic data indicated the structure of the new compound to be 12(E)
      labdene-15,16,(8beta)17-trial (miogatrial). Miogatrial and miogadial were potent
      inhibitors of human platelet aggregation and human 5-lipoxygenase (5-LOX). The
      sesquiterpene, polygodial, also exhibited strong inhibitory activity against
      human platelet aggregation and 5-LOX. On the other hand, galanals A and B did not
      have inhibitory activity in either experimental system. It thus appears that a 3
      formyl-3-butenal structure was essential for the potent inhibition of human
      platelet aggregation and human 5-LOX.

PMID- 17031031
TI  - Identification of a novel blue pigment as a melanoidin intermediate in the D
      xylose-glycine reaction system.
AB  - Some blue pigments were formed in the D-xylose (1 M)-glycine (0.1 M) reaction
      system. A novel blue pigment, designated as Blue-M2 (blue Maillard intermediate
      2), was identified as 5-[1,4-dicarboxymethyl-5-(2,3-dihydroxypropyl)-1,4
      dihydropyrrolo[3,2-b]pyrrole-2-ylmethylene]-1,4-dicarboxymethyl-2-{5-[N
      carboxymethyl(2,3,4-trihydroxytetrahydrofuran-2-yl)methylamino]-2-hydroxymethyl-4
      (1,2,3-trihydroxypropyl)tetrahydrofuran-3-yl}-4,5-dihydropyrrolo-[3,2-b]pyrrole-1
      ium. Blue-M2 is presumed to have been generated by the reaction between Blue-M1,
      which was identified as the major blue pigment in a previous paper (Hayase et
      al., Biosci. Biotechnol. Biochem., 63, 1512-1514 (1999)), and di-D
      xyluloseglycine. Blue pigments are important Maillard reaction intermediates
      through the formation of melanoidins.

PMID- 17031032
TI  - N-linked oligosaccharides of Aspergillus awamori feruloyl esterase are important
      for thermostability and catalysis.
AB  - A unique N-linked glycosylation motif (Asn(79)-Tyr-Thr) was found in the sequence
      of type-A feruloyl esterases from Aspergillus spp. To clarify the function of the
      flap, the role of N-linked oligosaccharides located in the flap region on the
      biochemical properties of feruloyl esterase (AwFAEA) from Aspergillus awamori
      expressed in Pichia pastoris was analyzed by removing the N-linked glycosylation
      recognition site by site-directed mutagenesis. N79 was replaced with A or Q. N
      glycosylation-free N79A and N79Q mutant enzymes had lower activity than that of
      the glycosylated recombinant AwFAEA wild-type enzyme toward alpha
      naphthylbutyrate (C4), alpha-naphthylcaprylate (C8), and phenolic acid methyl
      esters. Kinetic analysis of the mutant enzymes indicated that the lower catalytic
      efficiency was due to a combination of increased Km and decreased k(cat) for
      N79A, and to a considerably decreased k(cat) for N79Q. N79A and N79Q mutant
      enzymes also exhibited considerably reduced thermostability relative to the wild
      type.

PMID- 17031033
TI  - Removal of p-alkylphenols from aqueous solutions by combined use of mushroom
      tyrosinase and chitosan beads.
AB  - Enzymatic removal of p-alkylphenols from aqueous solutions was investigated
      through the two-step approach, the quinone conversion of p-alkylphenols with
      mushroom tyrosinase (EC 1.14.18.1) and the subsequent adsorption of quinone
      derivatives enzymatically generated on chitosan beads at pH 7.0 and 45 degrees C
      as the optimum conditions. This technique is quite effective for removal of
      various p-alkylphenols from an aqueous solution. The % removal values of 97-100%
      were obtained for p-n-alkylphenols with carbon chain lengths of 5 to 9. In
      addition, removal of other p-alkylphenols was enhanced by increasing either the
      tyrosinase concentration or the amount of added chitosan beads, and their %
      removal values reached >93 except for 4-tert-pentylphenol. This technique was
      also applicable to remove 4-n-octylphenol (4NOP) and 4-n-nonylphenol (4NNP) as
      suspected endocrine disrupting chemicals. The reaction of quinone derivatives
      enzymatically generated with the chitosan's amino groups was confirmed by the
      appearance of peaks for UV-visible spectrum measurements of the chitosan films
      incubated in the p-alkylphenol and tyrosinase mixture solutions. In addition, 4
      tert-pentylphenol underwent tyrosinase-catalyzed oxidation in the presence of
      hydrogen peroxide.

PMID- 17031034
TI  - Amino acid regions of family 45 endoglucanases involved in cotton defibrillation
      and in resistance to anionic surfactants and oxidizing agents.
AB  - In the detergent industry, fungal endoglucanases are used to release microfibrils
      from the surfaces of dyed cellulosic fabrics to enhance color brightness. Family
      45 endoglucanase (glycoside hydrolase family 45, GH45) EGL3 from Humicola grisea
      is more resistant to anionic surfactants and oxidizing agents than family 45
      endoglucanase RCE1 from Rhizopus oryzae, while in the present study, a catalytic
      domain of RCE1 had higher defibrillation activity on dyed cotton fabrics than did
      that of EGL3. To identify the amino acid regions involved in these properties, we
      compared the characteristics of RCE1, EGL3, and three chimeric endoglucanases, in
      which each of the three regions of the catalytic domain of EGL3 was replaced by
      the corresponding region of the catalytic domain of RCE1. Amino acids in the N
      terminal region were involved in resistance to anionic surfactants and oxidizing
      agents. Furthermore, amino acids in the region adjacent to the N-terminal region
      were involved in releasing microfibrils and in binding to dyed cotton fabrics,
      indicating that the binding of the amino acids in this region might be important
      in the release of microfibrils from dyed cotton fabrics.

PMID- 17031035
TI  - Dietary iron deficiency decreases serum osteocalcin concentration and bone
      mineral density in rats.
AB  - We investigated the effects of dietary iron deficiency on bone metabolism by
      measuring markers of bone turnover in rats. Twelve 3-week-old male Wistar-strain
      rats were fed a control diet or an iron-deficient diet for 4 weeks. Dietary iron
      deficiency decreased hemoglobin concentration and increased heart weight. Serum
      osteocalcin concentration, bone mineral content, bone mineral density, and
      mechanical strength of the femur were significantly lower in the iron-deficient
      group than in the control group. These results suggested that dietary iron
      deficiency affected bone, which might have been due to a decrease in bone
      formation in rats.

PMID- 17031036
TI  - Utilization study of stems and leaves of Tienchi Ginseng. I. Anti-hypertensive
      effect of stems and leaves of Tienchi Ginseng on stroke-prone spontaneously
      hypertensive rat (SHRSP).
AB  - Tienchi ginseng tea was prepared from stems and leaves of Tienchi ginseng which
      is a special product in China. The increase in systolic blood pressure (SBP) was
      significantly inhibited by the consumption of a 4% this tea solution as drinking
      water from the prehypertensive stage (6 weeks of age) in male stroke-prone
      spontaneously hypertensive rats (SHRSP). A similar intake from the hypertensive
      stage also showed an anti-hypertensive effect. In contrast, a similar intake had
      no effect on SBP of normotensive Wistar Kyoto rats. We found that the rhizome of
      Tienchi ginseng contained two types of saponin: 20(s)-protopanaxadiol (PPD) such
      as ginsenosides Rb(1) and Rd having a hypotensive effect, and 20(s)
      protopanaxatriol (PPT) such as ginsenosides Rg(1) and Re having a hypertensive
      effect. In contrast, the tea sample contained PPD and gamma-aminobutyric acid
      (GABA), but no PPT. These results suggest that drinking this tea infusion would
      be useful for controlling hypertension.

PMID- 17031037
TI  - Reduced immunogenicity of beta-lactoglobulin by conjugating with chitosan.
AB  - Bovine beta-lactoglobulin (beta-LG) was conjugated with chitosan (CHS) by means
      of a water-soluble carbodiimide to reduce the immunogenicity of beta-LG. Each
      beta-LG-CHS conjugate was purified by ion-exchange chromatography and hydrophobic
      chromatography. The conjugation between beta-LG and CHS was confirmed by SDS
      PAGE, the isoelectric point of the conjugate being higher than that of beta-LG.
      Two types of the beta-LG-CHS conjugate were obtained with molar ratios of beta-LG
      to CHS of 1:1 (F1) and 1:2 (F2). Structural analyses by fluorescence measurement,
      ELISA with monoclonal antibodies and retinol-binding activity indicated that the
      conjugates had almost maintained the native structure of beta-LG. The
      antigenicity of the beta-LG-CHS conjugates was similar to that of beta-LG in
      C3H/He mice. Reduction of the immunogenicity of beta-LG was achieved by
      conjugation with CHS. In particular, F2 showed very low immunogenicity. B cell
      epitopes of beta-LG and the conjugates recognized in C3H/He mice were determined
      with 15-mer multi-pin peptide; the linear epitope profiles of the conjugates were
      found to be similar to those of beta-LG, while the antibody response to each
      epitope was dramatically reduced. Conjugation of beta-LG with chitosan was
      effective for reducing the immunogenicity of beta-LG.

PMID- 17031038
TI  - Meat tenderizing effect of injecting encapsulated Ca2+ in liposome into rabbit
      before slaughter.
AB  - Encapsulated calcium in liposome (L-Ca) produced by using egg phosphatidyl
      choline in the laboratory was injected into rabbit to evaluate the effect of
      calcium injection on the ageing of meat. After injecting L-Ca into the blood
      vessels of rabbit to increase the Ca2+ concentration in the body for 24 h, the
      fragmentation rate of myofibrils was observed. The fragmentation rates in the
      loin from the control group and L-Ca injected group were 2.56% and 3.10% in 2
      days, 12.27% and 16.18% in 6 days, and 33.56% and 49.60% in 10 days, respectively
      (p<0.05). SDS-PAGE patterns of connectin and nebulin show that the total
      degradation of connectin by the control group took longer than 2-3 days, while it
      was within 1 day for the L-Ca-injected group. The control group took 8-10 days
      for nebulin, while the L-Ca-injected group took 2-3 days for total degradation.
      These results indicate that, injecting L-Ca into rabbit was effective for
      reducing the ageing period of meat without resulting in any physical shock or
      contamination.

PMID- 17031039
TI  - Oxygenases and dehalogenases: molecular approaches to efficient degradation of
      chlorinated environmental pollutants.
AB  - Microbial oxygenases and dehalogenases are key enzymes in the degradation of
      highly chlorinated compounds, which often become significant environmental
      pollutants. Oxygenases engineered by the methods of directed evolution exhibit
      enhanced degradation of PCBs and other chlorinated solvents such as
      trichloroethene and pentachloroethane. Dehalorespiration is an efficient
      dechlorination mechanism that is coupled with energy-yielding phosphorylation.
      Recently, a variety of chloroethene-dehalorespiring anaerobes have been isolated,
      and their reductive dehalogenases have been characterized in biochemical and
      genetic bases. This review describes our recent studies on dioxygenases and
      reductive dehalogenases.

PMID- 17031040
TI  - Temperature adaptation of Bacillus subtilis by chromosomal groEL replacement.
AB  - We investigated a temperature adaptation of Bacillus subtilis 168 in which
      chromosomal groEL was replaced with a psychrophilic groEL. This strain can grow
      at 50 degrees C but not at 51 degrees C, a temperature at which wild-type B.
      subtilis can grow. Using in vivo random mutagenesis by the B. subtilis mutator
      strain (mutS, mutM, mutY), two thermo-adaptants were isolated from the groEL
      substituted strain at 52 degrees C. They contained novel amino acid alterations
      in their ATP binding motif (T93I) and the inter-monomer contact (R285H) region of
      GroEL. These results suggest that GroEL participates in bacterial temperature
      adaptation.

PMID- 17031041
TI  - Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of
      Scutellaria baicalensis GEORGI.
AB  - The active ingredients of 'golden root' of Scutellaria baicalensis GEORGI (Huang
      Qin), a valuable traditional Chinese medicine, are polyhydroxyflavonoids, namely
      baicalein, oroxylin A and wogonin. With the objective of overcoming their poor
      solubility and to investigate their structure and activity relationships,
      baicaleinyl 7-O-sulfate was prepared, and extensive comparative antioxidative and
      anti-inflammatory tests were conducted. All the polyhydroxyflavonoids exhibited
      significant antioxidative and free-radical scavenging activities. In respect of
      their nitric oxide (NO) inhibition, wogonin was superior to all the other
      flavonoids, while oroxylin A was most potent in the inhibition of lipid
      peroxidation. Wogonin proved to be the most potent (82.9% inhibition, p<0.05) in
      its anti-inflammatory activity against carrageenan-induced rat hind paw edema.
      There was a correlation between the in-vivo anti-inflammatory activity and the in
      vitro antioxidative activities.

PMID- 17031042
TI  - Phenolic constituents of Celosia cristata L. susceptible to spinach root rot
      pathogen Aphanomyces cochlioides.
AB  - Cochliophilin A (5-hydroxy-6,7-methylenedioxyflavone, 1), known as a host
      specific attractant towards the zoospores of Aphanomyces cochlioides, a cause of
      root rot and damping-off diseases of Chenopodiaceae, was found in the
      Amaranthaceae plant, Celosia cristata, that is susceptible to the pathogen. The
      content of 1 in Celosia seedlings was quantified as 1.4 microg/g fresh weight. A
      new isoflavone, cristatein (5-hydroxy-6-hydroxymethyl-7,2'-dimethoxyisoflavone,
      2), and five known flavonoids were also identified.

PMID- 17031044
TI  - Algicidal diterpenes from the brown alga Dictyota dichotoma.
AB  - Bioassay-guided fractionation of an ethanol extract of the brown alga, Dictyota
      dichotoma, led to the isolation of a novel chlorine-containing perhydroazulene
      diterpene together with two known diterpenes, dictyolactone and sanadaol. The
      structure of the novel compound, named dictyol J, was elucidated on the basis of
      spectroscopic information. Dictyolactone showed the highest algicidal activity
      against red-tide phytoplanktons among the three isolated compounds.

PMID- 17031043
TI  - Chemoenzymatic synthesis of a MUC1 glycopeptide carrying non-natural sialyl TF
      beta O-glycan.
AB  - A MUC1 type of glycopeptide was synthesized by the 9-fluorenylmethoxycarbonyl
      (Fmoc) solid-phase peptide synthesis (SPPS) protocol using benzyl and benzylidene
      protected beta-D-Gal-(1-->3)-beta-D-GalNAc-Ser/Thr (TF-beta: a stereoisomer of
      the Thomsen-Friedenreich antigen). The synthetic glycopeptide was released from
      the resin with reagent K, and the resulting benzylated glycopeptide was
      deprotected under conditions of low-acidity trifluoromethanesulfonic acid (TfOH).
      The glycopeptide carrying duplicate non-natural O-glycans was dominant in the
      products, but was accompanied by a considerable amount of the glycopeptide
      missing one of the O-glycans. In contrast, the native alpha-glycoside was
      relatively stable under the acidic debenzylation conditions as shown by a
      parallel experiment with the glycopeptide involving alpha-D-GalNAc-Ser/Thr
      linkage. Enzymatic glycosylation with CMP-NeuAc was successful with both natural
      and non-natural O-glycans of the synthetic glycopeptide.

PMID- 17031045
TI  - Royal jelly stimulates bone formation: physiologic and nutrigenomic studies with
      mice and cell lines.
AB  - Royal jelly (RJ) has diverse physiological and pharmacological functions. We
      observed its weak estrogenic activity in the previous study. RJ stimulated the
      proliferation of mouse osteoblast-like MC3T3-E1 cells at 0.1 mg/ml, and the
      effect was blocked by the specific estrogen receptor antagonist ICI 182,780. The
      addition of 0.1-1.0 mg/ml RJ enhanced collagen production in culture medium. Oral
      administration of RJ to normal female mice for 9 weeks increased the ash content
      of their tibiae. DNA microarray analysis revealed significant changes in gene
      expression related to extracellular matrix formation when the femurs of mice fed
      RJ were analyzed. Quantitative reverse transcriptase-PCR (RT-PCR) confirmed up
      regulation of procollagen I alpha1 gene expression. These data suggest that RJ as
      a whole or some of its individual components stimulates production of type I
      collagen and other activities for bone formation through action on osteoblasts.

PMID- 17031046
TI  - Occurrence of novel nonmethylene-interrupted C24 polyenoic fatty acids in female
      gonad lipids of the limpet Cellana grata.
AB  - The occurrence of positional isomers of minor C(24) unsaturated fatty acids in
      female gonad lipids of the limpet Cellana grata was clarified by gas
      chromatography-mass spectrometry of the combination of their 4,4
      dimethyloxazoline and picolinyl ester derivatives. In this study, in addition to
      5,9-24:2, 9,15-24:2, 5,9,15-24:3, and 5,9,17-24:3, previously identified, 24:4n
      6, 24:5n-3, and four novel nonmethylene-interrupted fatty acids, 9,17-24:2,
      9,15,18-24:3, 5,9,15,18-24:4, and 5,9,15,18,21-24:5, were newly recognized. All
      C(24) unsaturated fatty acids detected were present only in triacylglycerols.

PMID- 17031047
TI  - Effects of chlorogenic acid and its metabolites on spontaneous locomotor activity
      in mice.
AB  - Chlorogenic acid possessed a weak caffeine-like psychostimulant property when
      assessed for its effect on spontaneous locomotor activity in mice. In the
      evaluation of the effects for the major metabolites of chlorogenic acid which
      were detected upon incubation with rat feces and/or excreted in urine after oral
      administration to rats, caffeic and m-coumaric acids were found to be the
      principal active metabolites, while the others contributed little to this
      caffeine-like psychostimulant activity.

PMID- 17031048
TI  - Effects of cadmium stress on growth, morphology, and protein expression in
      Rhodobacter capsulatus B10.
AB  - The effects of cadmium stress on growth, morphology, and protein expression were
      investigated in Rhodobacter capsulatus B10 using two-dimensional polyacrylamide
      gel electrophoresis and a scanning electron microscope with an energy dispersive
      X-ray spectrometer. The bacterium grew in the presence of 150 microM CdCl2 and
      highly induced heat-shock proteins (GroEL and Dnak), S-adenosylmethionine
      synthetase, ribosomal protein S1, aspartate aminotransferase, and
      phosphoglycerate kinase. Interestingly, the ribosomal protein S1 was
      proportionally expressed as the amount of cadmium in the medium, suggesting that
      S1 may be required for the repair of cadmium-mediated cellular damage. On the
      other hand, we identified five cadmium-binding proteins: 2-methylcitrate
      dehydratase, phosphate periplasmic binding protein, inosine-5'-monophosphate
      dehydrogenase/guanosine-5'-monophosphate reductase, inositol monophosphatase, and
      lytic murein transglycosylase. The cadmium-treated cells had a filamentous
      structure and contained less phosphorous than the untreated cells. We propose
      that these characteristics of the cadmium-treated cells may be due to the
      inactivation of the phosphate periplasmic binding protein and lytic murein
      transglycosylase by cadmium.

PMID- 17031049
TI  - Conversion of capsular polysaccharide, involved in pellicle formation, to
      extracellular polysaccharide by galE deletion in Acetobacter tropicalis.
AB  - Acetobacter tropicalis SKU1100 produces a pellicle-forming capsular
      polysaccharide (CPS), consisting of galactose, glucose, and rhamnose. We cloned
      the galE gene, a UDP-galactose synthesis gene, from A. tropicalis SKU1100 by PCR.
      A galE-disruptant was prepared and found not to produce CPS and thus not to form
      a pellicle under the static condition. Instead, the DeltagalE mutant secreted an
      extracellular polysaccharide (EPS), which was purified and found to have a unique
      character, different from the original CPS.

PMID- 17031050
TI  - Effect of dietary cyclic nigerosylnigerose on intestinal immune functions in
      mice.
AB  - We examined the dietary effects of cyclic nigerosylnigerose (CNN), a dietary
      indigestible oligosaccharide with four D-glucopyranosyl residues linked by
      alternating alpha-(1-->3)- and alpha-(1-->6) glucosidic linkages, on the
      intestinal immune function of mice, and the effects were compared with those of
      alpha-(1-->3)-linked oligosaccharide (nigerooligosaccharides, NOS) or alpha-(1-
      >6)-linked oligosaccharide (isomaltooligosaccharides, IMO). BALB/c mice were fed
      with 1-5% CNN, 5% IMO, or 12.5% NOS for 4 weeks, and the intestinal mucosal
      immune responses were determined. In the 1-5% CNN fed groups, the amounts of IgA
      in feces increased significantly. In addition, IgA, transforming growth factor
      beta1 (TGF-beta1), and interleukin-6 (IL-6) secretion by Peyer's patch (PP) cells
      were enhanced in CNN fed mice. In the 5% CNN group, pH in the cecum decreased,
      and the amounts of lactic acid and butyric acid increased. These findings were
      not observed in the NOS- or IMO-fed group of mice. They suggest that CNN
      supplementation changes the intestinal environment of microflora and indirectly
      enhances the immune function in the gut.

PMID- 17031051
TI  - Sake yeast suppresses acute alcohol-induced liver injury in mice.
AB  - Brewer's and baker's yeasts appear to have components that protect from liver
      injury. Whether sake yeast, Saccharomyces cerevisiae Kyokai no. 9, also has a
      hepatoprotective effect has not been examined. Here we show that sake yeast
      suppresses acute alcoholic liver injury in mice. Male C57BL/6 mice that had been
      fed a diet containing 1% sake yeast for two weeks received three doses of ethanol
      (5 g/kg BW). In the mice fed sake yeast, ethanol-induced increases in
      triglyceride (TG) and glutamate pyruvate transaminase (GPT) were significantly
      attenuated and hepatic steatosis was improved. In addition, sake yeast-fed mice
      showed a smaller decrease in hepatic S-adenosylmethionine (SAM) level and a
      smaller increase in plasma homocysteine (Hcy) level after ethanol treatment than
      the control mice, suggesting that a disorder of methionine metabolism in the
      liver caused by ethanol was relieved by sake yeast. These results indicate that
      sake yeast protects against alcoholic liver injury through maintenance of
      methionine metabolism in the liver.

PMID- 17031052
TI  - Determination of acylated anthocyanin in human urine after ingesting a purple
      fleshed sweet potato beverage with various contents of anthocyanin by LC-ESI
      MS/MS.
AB  - Eighty-seven healthy volunteers ingested a purple-fleshed sweet potato beverage
      with various contents of anthocyanin (beverage A; 22.1 mg/250 ml, B; 107.8, C;
      84.9). An acylated anthocyanin, peonidin 3-caffeoylsophoroside-5-glucoside, was
      detected in the urine 2 h after ingestion. The concentrations were 15.1+/-2.2
      microg/l of urine (mean+/-SEM), 46.6+/-5.3, and 53.3+/-2.2 for beverages A, B,
      and C respectively.

PMID- 17031053
TI  - Cloning, expression, and characterization of a chitinase from the chitinolytic
      bacterium Aeromonas hydrophila strain SUWA-9.
AB  - The chitinolytic bacterium Aeromonas hydrophila strain SUWA-9, which was isolated
      from freshwater in Lake Suwa (Nagano Prefecture, Japan), produced several kinds
      of chitin-degrading enzymes. A gene coding for an endo-type chitinase (chiA) was
      isolated from SUWA-9. The chiA ORF encodes a polypeptide of 865 amino acid
      residues with a molecular mass of 91.6 kDa. The deduced amino acid sequence
      showed high similarity to those of bacterial chitinases classified into family 18
      of glycosyl hydrolases. chiA was expressed in Escherichia coli and the
      recombinant chitinase (ChiA) was purified and examined. The enzyme hydrolyzed N
      acetylchitooligomers from trimer to pentamer and produced monomer and dimer as a
      final product. It also reacted toward colloidal chitin and chitosan with a low
      degree of deacetylation. When cells of SUWA-9 were grown in the presence of
      colloidal chitin, a 60 kDa-truncated form of ChiA that had lost the C-terminal
      chitin-binding domain was secreted.

PMID- 17031054
TI  - Purification, characterization, and gene analysis of cellulase (Cel8A) from
      Lysobacter sp. IB-9374.
AB  - An enzyme that has both beta-1,4-glucanase and chitosanase activities was found
      in the culture medium of the soil bacterium Lysobacter sp. IB-9374, a high lysyl
      endopeptidase-producing strain. The enzyme was purified to homogeneity from the
      culture filtrate using five purification steps and designated Cel8A. The purified
      Cel8A had a molecular mass of 41 kDa, as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. A pH optimum of 5.0 was found for the beta
      1,4-glucanase activity, and pH optima of 5.0 and 7.0 were found for the
      chitosanase activity. Nucleotide sequencing of the Cel8A gene yielded a deduced
      amino acid sequence that comprises a 33-amino acid, N-terminal signal peptide and
      a mature enzyme consisting of a 381-residue polypeptide with a predicted
      molecular mass of 41,241 Da. The amino acid sequence of the Cel8A, which contains
      the catalytic module of glycosyl hydrolase family 8, is homologous to beta-1,3
      1,4-D-glucanase from Bacillus circulans WL-12 and endoglucanase N-257 from B.
      circulans KSM-N257.

PMID- 17031055
TI  - Genes encoding small heat shock proteins of the silkworm, Bombyx mori.
AB  - Small heat shock protein (sHSP) is a family of ubiquitous polypeptides involved
      in a variety of physiological phenomena. From the silkworm, Bombyx mori, we
      isolated and sequenced the following cDNAs encoding sHSPs: shsp19.9, shsp20.1,
      shsp20.4, shsp20.8, shsp21.4, and shsp23.7. shsp21.4 was nearly twice as large in
      size as other shsps. The deduced amino acid sequence of sHSP21.4 was similar to
      that of Drosophila melanogaster CG14207-PA. Other sHSPs were highly similar to
      each other and, in a phylogenetic tree, formed a cluster including Plodia
      interpunctella alphaCP25. It was speculated that shsp21.4 has at least one intron
      in genome while other shsps do not. The transcripts of all shsps were subtle, but
      were constitutively detected in various tissues. Heat shock triggered a
      substantial increase in the transcripts other than shsp21.4. The B. mori sHSPs
      are perhaps classified into at least two groups: sHSP21.4 and others.

PMID- 17031056
TI  - Stimulatory effects of Pseudosasa japonica leaves on exercise performance.
AB  - The performance-enhancing effects of Pseudosasa japonica were investigated in
      mice using an adjustable-current water pool. Compared to the control group, a 1.5
      fold increase in swimming time was observed in the mouse group administered an
      80% ethanol extract (PJE) of the leaves of P. japonica. The blood lactate level,
      an important indicator of fatigue, was significantly lower (28%, P<0.05) in PJE
      group than in the control group. These results suggest that PJE possesses
      stimulatory effects that can enhance exercise endurance and reduce fatigue.

PMID- 17031057
TI  - The molecular phylogeny of the genus Rhizopus based on rDNA sequences.
AB  - In order to establish the molecular phylogeny of the genus Rhizopus, three
      molecules of the ribosomal RNA-encoding DNA (rDNA), complete 18S, internal
      transcribed spacer (ITS)1-5.8S-ITS2, and 28S D1/D2 regions of all the species of
      the genus were sequenced. Phylogenetic trees showed three major clusters
      corresponding to the three groups in the current morphological taxonomy,
      microsporus-group, stolonifer-group, and R. oryzae. R. stolonifer var. lyococcos
      was clustered independently from the major clusters. R. schipperae clustered
      differently in all trees. Strains of R. sexualis had multiple ITS sequences. A.
      rouxii clustered with R. oryzae. These results indicate the possibility of
      molecular identification of species groups using rDNA sequencing.
      Reclassification of the genus might be appropriate.

PMID- 17031058
TI  - Identification of Saccharomyces cerevisiae ribosomal protein L3 as a target of
      curvularol, a G1-specific inhibitor of mammalian cells.
AB  - The cellular target of curvularol, a G1-specific cell-cycle inhibitor of
      mammalian cells, was identified by a genetic approach in Saccharomyces
      cerevisiae. Since the wild-type W303 strain was highly resistant to curvularol, a
      drug hypersensitive parental strain was constructed in which various genes
      implicated in general drug resistance had been disrupted. Curvularol resistant
      mutants were isolated, and strains that exhibited a semi-dominant, curvularol
      specific resistance phenotype were selected. All five strains examined were
      classified into a single genetic complementation group designated YCR1. A mutant
      gene responsible for curvularol resistance was identified as an allele of the
      RPL3 gene encoding the ribosomal protein L3. Sequence analysis of the mutant
      genes revealed that Trp255Cys and Trp255Leu substitutions of Rpl3p are
      responsible for curvularol resistance. Rpl3p mutants in which Trp255 residue was
      replaced by other amino acids were constructed. All of these replacements led to
      varying degrees of increased resistance to curvularol and growth defects.

PMID- 17031059
TI  - Antihyperglycemic activity of herb extracts on streptozotocin-induced diabetic
      rats.
AB  - We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa,
      Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose
      levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin
      (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus
      verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose
      levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of
      glucose oxidation in blood, were also lowered by Rhus verniciflua extract
      supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts
      significantly reduced TBARS levels versus diabetic controls. Serum concentrations
      of liver-function marker enzymes, GOT and GPT, were also restored by Rhus
      verniciflua (50 mg/kg) supplementation in diabetic rats.

PMID- 17031060
TI  - Enantioselective synthesis of the (1S,5R)-enantiomer of litseaverticillols A and
      B.
AB  - An enantioselective synthesis of the (1S,5R)-enantiomer of litseaverticillols A
      and B was accomplished in line with our previously reported synthetic pathway for
      their (1R,5S)-enantiomer. The use of "EtSCeCl2" prepared from EtSLi and CeCl3,
      instead of previously employed EtSLi itself, for the formation of thiol ester
      intermediates prevented any undesirable epimerization occurring in the process.

PMID- 17031061
TI  - Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in
      rats.
AB  - The hyperhomocysteinemia induced by a dietary addition of 1% methionine was
      significantly suppressed by the concurrent addition of 1% glycine or 1.4% serine
      to the same degree. The methionine-induced increase in the hepatic concentration
      of methionine metabolites was significantly suppressed by glycine and serine, but
      the hepatic cystathionine beta-synthase activity was not enhanced by these amino
      acids. When the methionine-supplemented diet was changed to the methionine plus
      glycine or serine diet, the plasma homocysteine concentration rapidly decreased
      during and after the first day. The hyperhomocysteinemia induced by an
      intraperitoneal injection with methionine was also suppressed by concurrent
      injection with glycine or serine, although the effect of serine was significantly
      greater than that of glycine. These results indicate that glycine and serine were
      effective for suppressing methionine-induced hyperhomocysteinemia: serine and its
      precursor glycine are considered to have elicited their effects mainly by
      stimulating cystathionine synthesis by supplying serine, another substrate for
      cystathionine synthesis.

PMID- 17031062
TI  - Synthesis of gerfelin and related analogous compounds.
AB  - Gerfelin, an inhibitor of human geranylgeranyl diphosphate (GGPP) synthase that
      has been isolated from a culture broth of Beauveria felina QN22047, was
      synthesized in 4 and 3 steps starting from 2,4-dihydroxy-6-methylbenzoic acid and
      3,4,5-trihydroxytoluene, respectively. An effective ligand, 2-(di-tert
      butylphosphino)biphenyl, was used in the palladium-catalyzed diaryl ether-forming
      reaction. Five analogous compounds of gerfelin were also synthesized for a study
      of the structure-activity relationship.

PMID- 17031063
TI  - Antioxidants in fruits and vegetables: a study of cellular availability and
      direct effects on human DNA.
AB  - The effects of several types of whole fruits and vegetables on human lymphocytic
      DNA were investigated by using two versions of the comet assay. The total
      antioxidative capacity, as the FRAP value, and ascorbic acid (AA) content were
      also measured to explore the relationship between the effect and antioxidant
      content.

PMID- 17031064
TI  - Partial replacement of waxy cornstarch by recrystallized amylose retards the
      development of insulin resistance in rats.
AB  - We examined in rats whether or not the prolonged ingestion of recrystallized
      amylose (RCA) would prevent the development of insulin resistance. Rats were fed
      on a diet containing waxy cornstarch (WCS) as carbohydrate or a diet containing
      30% RCA in place of WCS for 18 wk. Glucose tolerance test (GTT) was conducted at
      every four weeks. On wk 16, the plasma insulin response as assessed by the area
      under the curve was lower in the RCA diet group than in the WCS diet group. The
      fasting plasma insulin level tended to increase over time in both groups, but was
      lower in the RCA diet group on wk 16. An autopsy revealed that the adipose tissue
      mass and serum free fatty acid concentrations were significantly higher in the
      WCS diet group. The results suggest that prolonged ingestion of RCA had the
      effect of slowing the development of insulin resistance through a lower
      concentration of serum free fatty acids, presumably due to the prevention of
      adipocyte hypertrophy.

PMID- 17031065
TI  - Determination of the absolute configuration of quercivorol, (1S,4R)-p-menth-2-en
      1-ol, an aggregation pheromone of the ambrosia beetle Platypus quercivorus
      (Coleoptera: Platypodidae).
AB  - A pair of enantiomers of trans-p-menth-2-en-1-ol, an aggregation pheromone of
      Platypus quercivorus, was synthesized from (S)- and (R)-limonene. The retention
      time of the aggregation pheromone from the insect coincided with that of (1S,4R)
      p-menth-2-en-1-ol synthesized from (S)-limonene from GC analyses with a chiral
      column, enabling the absolute configuration of the aggregation pheromone to be
      determined as (1S,4R).

PMID- 17031066
TI  - Azelnidipine down-regulates renal angiotensin-converting enzyme and
      mineralocorticoid receptor mRNA in diabetic hypertensive rats.
AB  - Effects of a new lipophilic L-type calcium channel blocker, azelnidipine, on the
      expression of molecular components of the renin-angiotensin-aldosterone system
      (RAAS) were assessed. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a
      model of diabetes with hypertension, and their lean littermates, Long-Evans
      Tokushima Otsuka (LETO) rats, were treated with azelnidipine for 2 weeks. The
      renal cortical mineralocorticoid receptor mRNA in OLETF was higher than in LETO,
      but was suppressed (P<0.05) by azelnidipine. Renal cortical angiotensin
      converting enzyme mRNA of OLETF was lower than that of LETO rats, and it was
      further suppressed by azelnidipine (P<0.05). Azelnidipine can down-regulate the
      gene expression of molecular components of RAAS.

PMID- 17031067
TI  - Increase in expression of alpha1 and alpha2/delta1 subunits of L-type high
      voltage-gated calcium channels after sustained ethanol exposure in cerebral
      cortical neurons.
AB  - Previous reports revealed up-regulation of L-type high voltage-gated calcium
      channels (HVCCs) in mouse brains with ethanol physical dependence. We
      investigated mechanisms of enhancement of L-type HVCC function using mouse
      cerebrocortical neurons exposed to 50 mM ethanol for 3 days and the brains of
      mouse physically dependent on ethanol. Ethanol facilitated 30 mM KCl-stimulated
      (45)Ca(2+) influx in dose- and duration-dependent manners, which was abolished by
      nifedipine, an inhibitor specific to L-type HVCCs, but not by inhibitors for
      other types of HVCCs. Increase in [(3)H]PN200-110 binding to the particulate
      fractions from the ethanol-treated neurons was due to increased B(max) value with
      no changes in K(d) value. Western blot analysis showed the increased expression
      of alpha1C, alpha1D, and alpha2/delta1 subunits with decreased beta4 subunit
      expression and no changes in expressions of alpha1A, alpha1B, alpha1F, and alpha2
      subunits. A similar pattern of the changes in the expression of these subunits of
      L-type HVCCs were observed in the cerebral cortex from mouse with ethanol
      physical dependence. These results indicate that sustained ethanol exposure to
      the neurons induces up-regulation of L-type HVCCs, which is due to increased
      expressions of alpha1C, alpha1D, and alpha2/delta1 subunits, and produces no
      alterations in P/Q- and N-type HVCC functions.

PMID- 17031068
TI  - The elucidation of the mechanism of weight gain and glucose tolerance
      abnormalities induced by chlorpromazine.
AB  - Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the
      role of adipocytokines secreted from adipocytes in the development of metabolic
      syndrome has received attention. The aim of this study was to investigate the
      effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and
      adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose
      (Suc group), 15% sucrose and Cp at 7.5 mg/kg per day (Suc + Cp group), or Cp
      alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc
      + Cp groups were significantly higher than in the control (Cont) group. Fasting
      insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher
      than in the Cont group. The adiponectin level in the Suc group was significantly
      higher than in the Cont group, although the adiponectin level in the Suc + Cp
      group was not. Furthermore, the plasma tumor necrosis factor (TNF)-alpha level in
      the Suc + Cp group was significantly higher than in the Suc group. These data
      suggest that Cp inhibits the compensatory response of adiponectin with respect to
      obesity due to increased expression of plasma TNF-alpha level. Cp may exert more
      harmful effects on the glucose level and insulin resistance than on other
      factors, which may be one of the mechanisms responsible for the metabolic
      syndrome induced by antipsychotic agents.

PMID- 17031069
TI  - Pharmacological profiles of the novel analgesic M58996 in rat models of
      persistent and neuropathic pain.
AB  - We investigated the effects of 4-(N-{1-[2-(4-cyanophenyl)ethyl]-4
      hydroxypiperidin-4-ylmethyl}-N-methylamino)benzoic acid monohydrochloride
      (M58996), a novel analgesic, on persistent and neuropathic pain in rats. In the
      formalin test, oral M58996 (0.3 - 10 mg/kg) reduced nociceptive behaviors only in
      the late phase. In the neuropathic pain model, oral M58996 (1 - 10 mg/kg)
      attenuated mechanical allodynia and heat hyperalgesia in the nerve-injured paw
      without affecting normal responses of the uninjured paw. High doses (10 - 100
      mg/kg) of oral M58996 did not influence normal motor function. Thus, M58996 had a
      wide dose range showing antinociceptive, antiallodynic, and antihyperalgesic
      effects without motor dysfunction. In addition, we studied the possible
      mechanisms involved in the M58996-induced antinociception. The antinociceptive
      effect of M58996 was reversed by intrathecal pertussis toxin, an inhibitor of the
      inhibitory- and other-GTP-binding protein (G(i/o) protein), but not by
      subcutaneous naloxone, an opioid-receptor antagonist. This effect was also
      reversed by intracerebroventricular or intrathecal tropisetron, a 5
      hydroxytryptamine(3) (5-HT(3))-receptor antagonist, and intraperitoneal
      bicuculline, a gamma-aminobutyric acid(A) (GABA(A))-receptor antagonist. These
      results suggest that M58996 produces its antinociceptive effect by a pertussis
      toxin-sensitive G protein mechanism. In addition, the GABA released by the
      activation of supraspinal and/or spinal 5-HT(3) receptors is likely to contribute
      to the M58996-induced antinociception.

PMID- 17031070
TI  - Lig-8, a bioactive lignophenol derivative from bamboo lignin, protects against
      neuronal damage in vitro and in vivo.
AB  - Lig-8, a lignophenol derivative from bamboo lignin, potently suppresses oxidative
      stress-induced apoptosis. Here, we first examined in vitro whether lig-8 protects
      against neuronal damage induced by oxygen-glucose deprivation (OGD) followed by
      reoxygenation, tunicamycin [endoplasmic reticulum (ER)-stress inducer], or PSI
      (proteasome inhibitor). In pheochromocytoma (PC12) cell cultures, lig-8 (1 to 30
      microM) concentration-dependently inhibited OGD- and tunicamycin (2 microg/ml)
      induced cell deaths (significant at >/=3 microM and >/=1 microM, respectively).
      In human neuroblastoma (SH-SY5Y) cell culture, the PSI-induced apoptotic cell
      death and fusion protein accumulation (revealing reduced proteasome activity) was
      inhibited by lig-8 (30 microM). On the other hand, lig-8 at 30 microM alone did
      not affect any proteasome activity under resting conditions. In vivo, lig-8 (0.1
      nmol/eye) reduced intravitreal N-methyl-D-aspartate (NMDA, 20 nmol)-induced
      retinal damage (decreases in retinal ganglion cells and inner plexiform layer
      thickness). Hence, lig-8 protects, partly by inhibiting excessive ER-stress,
      against neuronal damage in vitro and in vivo.

PMID- 17031071
TI  - Inverse agonist activity of sarpogrelate, a selective 5-HT2A-receptor antagonist,
      at the constitutively active human 5-HT2A receptor.
AB  - Mutations producing constitutively active G-protein coupled receptors have been
      found in the pathophysiology of several diseases, implying that inverse agonists
      at the constitutively active receptors may have preferred therapeutic
      applications. Because of the involvement of 5-HT(2A) receptors in mediating many
      cardiovascular diseases, constitutively active mutants of the 5-HT(2A) receptor
      may be responsible for the disease states. Thus, the purpose of the present study
      was to investigate the inverse agonist activity of sarpogrelate, a selective 5
      HT(2A)-receptor antagonist, and its active metabolite, M-1; and we compared their
      activities with those of other 5-HT(2A)-receptor antagonists such as ritanserin,
      ketanserin, and cyproheptadine. Using a constitutively active mutant (C322K) of
      the human 5-HT(2A) receptor, we demonstrated that like other 5-HT(2A)-receptor
      antagonists, sarpogrelate acts as a potent inverse agonist by significantly
      reducing basal inositol phosphate levels. However, there were no significant
      differences between sarpogrelate and other 5-HT(2A)-receptor antagonists for
      their inverse agonist activity. Compared with the wild type receptor, mutant
      receptor displayed significantly higher affinity for 5-HT and lower affinity for
      sarpogrelate. These results indicate that stabilization of the inactive
      conformation of the 5-HT(2A) receptor may be a key component of the mechanism of
      action of sarpogrelate.

PMID- 17031072
TI  - Protective effect of prostaglandin EP4-receptor agonist on anti-glomerular
      basement membrane antibody-associated nephritis.
AB  - Prostaglandin E(2)-receptor subtypes, EP(1), EP(2), EP(3), and EP(4), are present
      in the kidney. The aim of this study was to elucidate the anti-nephritic effect
      of an EP(4)-receptor agonist on an experimental nephritic model. Mice were
      injected i.v. with anti-glomerulus antiserum to induce nephritis. Nephritic
      glomeruli generated more prostaglandin E(2) (2.6 and 0.7 ng) and less cyclic AMP
      than normal glomeruli (11 and 26 pmol). The production of cyclic AMP in nephritic
      glomeruli increased 67% in response to AE1-329, an EP(4) agonist, at 10(-5) M.
      Nephritic glomeruli expressed a lesser amount of mRNA of prostaglandin E(2)
      receptor subtypes as compared with normal glomeruli. AE1-329 was administered
      s.c. at 100 microg/kg per day for 3 weeks. AE1-329 suppressed the increase in
      creatinine and cholesterol compared to those in the control nephritic mice. AE1
      329-treated nephritic mice had less crescentic glomeruli and less deposition of
      rabbit IgG (anti-glomerular basement membrane antibody) in glomeruli than the
      control mice. AE1-329 prevented the development of glomerulonephritis. These
      findings suggest that EP(4)-receptor agonists are a promising drug to prevent the
      development of glomerulonephritis.

PMID- 17031073
TI  - Insufficient expression of cyclooxygenase-2 protein is associated with retarded
      degradation of aggregated protein in diabetic glomeruli.
AB  - To elucidate the involvement of cyclooxygenase (COX) in degradation of aggregated
      protein in diabetic glomeruli, we used streptozotocin (STZ)-induced diabetic mice
      and aggregated bovine serum albumin (a-BSA) as a model protein. There was a
      higher deposition of a-BSA in diabetic glomeruli compared to normal glomeruli 18
      h after a-BSA injection at 4 and 8 weeks after STZ. Degradation of a-BSA was
      confirmed using isolated glomeruli. Diabetic glomeruli produced prostaglandin
      E(2) (PGE(2)) more than normal glomeruli in the basal level at 8 weeks. a-BSA
      caused further increase of PGE(2) production in normal glomeruli, but not in
      diabetic glomeruli. Niflimic acid, a selective COX-2 inhibitor, reduced PGE(2)
      production of normal glomeruli in the a-BSA loading group, but not that in the
      control group. In diabetic glomeruli, niflimic acid reduced PGE(2) production in
      both the control group and a-BSA loading group. In normal glomeruli, a-BSA
      increased expressions of both COX-2 mRNA and protein. However, in diabetic
      glomeruli, a-BSA increased COX-2 mRNA expression but not COX-2 protein
      expression. These results suggest that retarded degradation of aggregated protein
      in diabetic glomeruli is associated with lack of further expression of COX-2
      protein and further production of PGE(2) in response to aggregated protein.

PMID- 17031074
TI  - Beta-blockers show inverse agonism to a novel constitutively active mutant of
      beta1-adrenoceptor.
AB  - We obtained a new mutant of the beta(1)-adrenergic receptor (beta(1)-AR) by point
      mutations that can constitutively activate beta(1)-AR. Aspartate104 of the
      beta(1)-AR in the 2nd transmembrane was replaced with alanine. The beta(1)-AR
      mutant expressed in human embryonic kidney (HEK)-293 cells displayed high level
      of constitutive activity with respect to wild-type (P<0.05), which could be
      partially inhibited by some beta-blockers. The constitutive activity of the
      mutant was confirmed by the finding that the enhanced activity is dependent on
      the level of receptor expression. The results of this study might have
      interesting implications for future studies aiming at elucidating the activation
      process of the beta(1)-AR as well as the mechanism of action of beta-blockers.

PMID- 17031075
TI  - Signaling pathways involved in the cardioprotective effects of cannabinoids.
AB  - The aim of the present article is to review the cardioprotective properties of
      cannabinoids, with an emphasis on the signaling pathways involved. Cannabinoids
      have been reported to protect against ischemia in rat isolated hearts, as well as
      in rats and mice in vivo. Although these effects have been observed mostly with a
      pre-treatment of a cannabinoid, we report that the selective CB(2)-receptor
      agonist JWH133 is able to reduce infarct size when administered either before
      ischemia, during the entire ischemic period, or just upon reperfusion. Little is
      known about the signaling pathways involved in these cardioprotective effects.
      Likely candidates include protein kinase C (PKC) and mitogen-activated protein
      kinases (MAPK) since they are activated during ischemia-reperfusion and
      contribute to the protective effect ischemic preconditioning. The use of
      pharmacological inhibitors suggests that PKC, p38 MAPK, and p42/p44 MAPK (ERK1/2)
      contribute to the protective effect of cannabinoids. In addition, perfusion with
      JWH133 in healthy hearts caused an increase in both p38 MAPK phosphorylation
      level and activity, whereas the CB(1)-receptor agonist ACEA was associated with
      an increase in the phosphorylation status of both ERK1 and ERK2 without any
      change in activity. During ischemia, both agonists doubled p38 MAPK activity,
      whereas ERK1/2 phosphorylation level and activity during reperfusion were
      enhanced only by the CB(1)-receptor agonist. Finally, although nitric oxide (NO)
      was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an
      apparently controversial effect on myocardial survival, our data suggest that NO
      may contribute to the cardioprotective effect of some cannabinoids.

PMID- 17031077
TI  - Difficult-airway management need not be difficult!

PMID- 17031076
TI  - Development of genetically engineered mice lacking all three nitric oxide
      synthases.
AB  - Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple
      biological actions under both physiological and pathological conditions. NO is
      synthesized by three different isoforms of NO synthase (NOS): neuronal,
      inducible, and endothelial NOSs. Due to the substantial compensatory interactions
      among the NOS isoforms, the ultimate roles of endogenous NO in our body still
      remain to be fully elucidated. To address this point, we have successfully
      developed mice in which all three NOS genes are completely disrupted. NOS
      expression and activities were totally absent in the triply n/i/eNOS(-/-) mice
      before and after treatment with lipopolysaccharide. While the triply n/i/eNOS(-/
      ) mice were viable, their survival and fertility rates were markedly reduced as
      compared with wild-type mice. The phenotypes of those mice that we first noticed
      were polyuria, polydipsia, and renal unresponsiveness to vasopressin,
      characteristics consistent with nephrogenic diabetes insipidus. We subsequently
      observed that in those mice, arteriosclerosis is spontaneously developed with a
      clustering of cardiovascular risk factors. These results provide the first
      evidence that the systemic deletion of all three NOSs causes a variety of
      cardiovascular diseases in mice, demonstrating a critical role of the endogenous
      NOSs system in maintaining cardiovascular homeostasis.

PMID- 17031078
TI  - Unanticipated difficult intubation.
AB  - PURPOSE OF REVIEW: While there are many predictors of difficult laryngoscopic
      intubation, they all have a low positive predictive value. Therefore,
      unanticipated difficult laryngoscopic intubation will likely occur in our day-to
      day practice. This review discusses recent developments in alternative airway
      devices and techniques in addressing these difficulties. RECENT FINDINGS: There
      is emerging evidence to suggest that new supraglottic devices are useful rescue
      appliances, particularly for unanticipated difficulties in laryngoscopic
      intubation. Other new intubating devices, including the Glidescope, may also play
      an important role in the management of patients with unanticipated difficult or
      failed laryngoscopic intubation. SUMMARY: The evidence to date does not always
      arm us with the ability to predict a difficult laryngoscopic intubation.
      Therefore, it is imperative that we equip ourselves with devices and techniques
      that will help us to maintain effective oxygenation and ventilation in a safe
      manner in the face of such failure.

PMID- 17031079
TI  - Algorithms for management of the difficult airway.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine recent evidence for
      the management of the difficult airway. RECENT FINDINGS: Recent findings still
      recommend the importance of a predefined, simple strategy for both the
      anticipated and unanticipated difficult airway. For the former, awake fiberoptic
      intubation is still the 'gold standard'. For management of the unanticipated
      difficult airway, the use of the laryngeal mask airway (LMA), intubating
      laryngeal mask airway (ILMA), the 'gum elastic bougie' and fiber-optics are
      recommended. If intubation and ventilation fails, cannula or surgical
      cricothyroidotomy should be an early consideration. SUMMARY: This review of
      algorithms for management of the difficult airway strengthens several generally
      accepted crucial points. What is always needed is expertise, which one can only
      get and maintain by daily practice.

PMID- 17031080
TI  - Trends in tracheal intubation: emphasis on the difficult airway.
AB  - PURPOSE OF REVIEW: This review will summarize the progress made during the last
      year in improving difficult-airway management. RECENT FINDINGS: The UK Difficult
      Airway Society have published extensive guidelines for the management of
      unanticipated difficult intubation in the unobstructed adult patient. That such
      an approach is useful has been demonstrated in an independent study which showed
      that simple guidelines using familiar equipment will solve the majority of
      intubation difficulties likely to be encountered. However, their limitation lies
      in the fact that the worst-case scenario (i.e. inability to ventilate or
      intubate) is so rare that it cannot be studied systematically. It is postulated
      that a different approach geared to understanding the causes of difficulties with
      intubation may provide an alternative strategy for providing an evidence base.
      SUMMARY: Significant steps have been made in our management of the difficult
      airway, and the majority of the problems encountered can be solved with recourse
      to simple published guidelines.

PMID- 17031081
TI  - Recent trends in tracheal intubation: emphasis on the difficult airway.
AB  - PURPOSE OF REVIEW: Difficult airways can lead to critical incidents during
      anaesthesia, and death. Although many cases can be anticipated, some still go
      undiscovered before induction, thereby exposing the patient to unexpected risks
      and the anaesthesiologist to unexpected challenges. In addition to improving
      prediction of difficult airways, education for skill acquisition and management
      planning, and a quest for superior management techniques and airway tools are of
      the utmost importance in preventing airway catastrophes. RECENT FINDINGS: We
      review recent advances in predicting difficult airways in special population
      groups that are known to have a higher incidence of difficult airway. Education,
      exercising airway skills, management planning with both predicted and unpredicted
      difficult airways, and the need for adherence to algorithms for management of
      difficult airway are emphasized as key to successful management. Finally, recent
      developments in airway management techniques and new airway devices are
      summarized. SUMMARY: Improving reproducibility and reliability in predicting a
      difficult airway may limit the number of unpredicted difficult intubations. A
      safer approach to management of the difficult airway can be achieved by improving
      airway management skills and adhering to universally accepted and proven airway
      algorithms, including developing approaches to management of predicted and
      unpredicted difficult airways. Improving on existing airway techniques and tools
      (of which there are many), rather than creating new devices, is a desirable trend
      that may contribute to safer airway management in the future.

PMID- 17031082
TI  - Laryngeal mask airway and the difficult airway.
AB  - PURPOSE OF REVIEW: To present recent advances in the role of the laryngeal mask
      airway (LMA) and its newer modifications in the management of difficult airway.
      RECENT FINDINGS: The principles of management of a difficult airway remain the
      same, but the advent of the intubating LMA (ILMA) and Proseal LMA (PLMA) has
      provided a better choice in such situations. While fiberoptic intubation remains
      the preferred choice of many anaesthesiologists, the ILMA provides equal or
      better conditions for intubation when compared with the awake technique. The PLMA
      with its better safety profile is proving valuable in the emergency scenario.
      SUMMARY: ILMA and PLMA have been shown to be effective in the management of
      difficult airway. We recommend that training in the use of these devices be made
      mandatory.

PMID- 17031083
TI  - Alternative management techniques for the difficult airway: optical stylets.
AB  - PURPOSE OF REVIEW: We present the newest devices being promoted for difficult
      airway management. Our focus is on optical stylets which offer a forward view
      from the stylet end positioned within the tip of the endotracheal tube. RECENT
      FINDINGS: Reports suggest that these devices are mastered quickly and offer
      effective airway management aid. Available in adult and pediatric sizes they are
      economically priced at approximately US$ 3000. SUMMARY: Generally favorable
      experience with use of optical stylets continues to be reported. Our survey of
      clinicians' opinions reflects our own experience; these devices are unique and
      are attractive adjuncts to standard- and difficult-airway carts.

PMID- 17031084
TI  - Alternative management techniques for the difficult airway: esophageal-tracheal
      Combitube.
AB  - PURPOSE OF REVIEW: To summarize knowledge about the esophageal-tracheal Combitube
      in emergency medicine and anesthesia, with special emphasis on uncommon
      indications. Papers published between August 2003 and July 2004 are reviewed.
      RECENT FINDINGS: Tracheal intubation in the field is difficult and success rates
      are dependent upon training level (90-98%). Therefore, the esophageal-tracheal
      Combitube has been recommended for emergency ventilation after failed tracheal
      intubation with success rates of about 90%, even when performed by emergency
      medical technicians. Combitube insertion is easy to learn, but practice is
      necessary to retain skills. Use of this device has also been recommended for
      ventilatory support during routine anesthesia. Combitube ventilation is
      successful in over 96% of patients, with minimal trauma. Since only a small
      percentage of American anesthesiologists are familiar with the Combitube (<50%),
      using the device in anesthesia care may improve the skills required during
      emergency airway management. Blood gases are in the range of those obtained
      during endotracheal tube ventilation and aspiration prophylaxis is at least as
      good as that of the laryngeal mask airway. Successful uncommon uses of the device
      have also been recommended, for example, Combitube ventilation in
      craniomaxillomandibular surgery via the submental route and insertion of the
      device in a burns patient with minimal mouth opening and significant tracheal
      stenosis after long-term ventilation. SUMMARY: The esophageal-tracheal Combitube
      is a useful and efficient alternative airway characterized by high success rates
      in emergency situations. We recommend the use of a laryngoscope for insertion and
      strict adherence to the manufacturer's guidelines in order to maximize success
      and minimize potential injury.

PMID- 17031085
TI  - The Williams Airway Intubator, the Ovassapian Airway and the Berman Airway as
      upper airway conduits for fibreoptic bronchoscopy in patients with difficult
      airways.
AB  - PURPOSE OF REVIEW: In this article we will summarize the available information on
      airways that have been suggested to provide a conduit for the bronchoscope in its
      passage through the upper airway during fibreoptic intubation. RECENT FINDINGS:
      The Williams Airway Intubator and the Berman Oropharyngeal Airway appear to be
      more likely to provide a conduit for the bronchoscope than the Ovassapian
      Fibreoptic Intubating Airway. SUMMARY: Though the Williams Airway Intubator and
      the Berman Oropharyngeal Airway are superior in this role, all the airways
      discussed here have major deficiencies in their function. Further research is
      needed in this field to meet the requirements of endoscopists in situations when
      it is crucial that equipment reliably fulfils its function.

PMID- 17031086
TI  - Simulation and airway-management training.
AB  - PURPOSE OF REVIEW: Simulators can be used to teach simple technical skills or
      used in more realistic settings to teach or assess various cognitive/affective
      skills. Although simulators have become widespread, their use and efficacy in
      these various areas have not been delineated and are still being explored. This
      review will discuss the present state of using medical simulation for airway
      management training. RECENT FINDINGS: Airway management includes both specialized
      technical skills and higher-order cognitive skills and behaviors. Since no one
      simulator is capable of covering all the functions necessary to teach these
      varied skills, medical specialists will need to train on a couple of different
      simulators. Now widely accepted in medical education, simulator training is being
      mandated in certain situations at some institutions because of a belief that it
      alters the physician. In this article its efficacy in teaching the specific
      psychomotor skills of bronchoscopy were validated but its use in teaching higher
      cognitive skills remained inconclusive. SUMMARY: Simulators are here to stay.
      Presently their usage in teaching psychomotor skills has scientific validity in
      specific tasks but their efficacy for teaching higher-order cognitive skills is
      still evolving. Future studies will continue to delineate the usage in different
      areas by studying the outcome in skills training and retention.

PMID- 17031087
TI  - The carrier gas in anaesthesia: nitrous oxide/oxygen, medical air/oxygen and pure
      oxygen.
AB  - PURPOSE OF REVIEW: The gas passing the module for the delivery of inhalation
      anaesthetics and carrying vapourized anaesthetics into the breathing system is
      called the carrier gas. Oxygen is the absolutely indispensable component of the
      carrier gas. Additive gaseous components can be medical air (nitrogen), nitrous
      oxide, cyclopropane, or xenon, the latter three being anaesthetic gases
      themselves. Cyclopropane is not used any more and xenon is not approved as a
      medical gas yet, leaving medical air and nitrous oxide as the only currently
      available adjuncts to oxygen. RECENT FINDINGS: As review articles on nitrous
      oxide recommend unequivocally not using this gas routinely, and many
      anaesthetists already consistently omit any use of this gas, the alternative
      carrier gases are either a mixture of medical air and oxygen or pure oxygen. A
      nitrogen/oxygen mixture is absolutely inert with respect to metabolism or
      environment; there are no contraindications or shortcomings at all. The use of
      pure oxygen will result in high oxygen concentrations, improving the patients'
      safety by increasing the pulmonary oxygen reservoir and rendering impossible the
      development of hypoxic gas mixtures within the breathing system. Whether the
      incidence of postoperative wound infections or postoperative nausea and vomiting
      is reduced by perioperative hyperoxia is still under scientific discussion. In
      general, the use of high oxygen concentrations over a period of 6-8 h is not
      harmful for the patient, assuming the performance of recruitment manoeuvres,
      consistent use of positive end-expiratory pressure, and thorough observance of
      the contraindications that can result from the increased vulnerability of tissues
      to hyperoxia. SUMMARY: Nitrous oxide should not be used routinely as a component
      of the carrier gas any more. A mixture of medical air and oxygen must be
      acknowledged to be the gold standard. Pure oxygen may be used as a carrier gas if
      medical air or properly performing flow controls for medical air are not
      available.

PMID- 17031088
TI  - Capnometry in the spontaneously breathing patient.
AB  - PURPOSE OF REVIEW: Capnography has been used in the operating room by
      anesthesiologists for over a decade. Along with pulse oximetry, it has reduced
      anesthesia-related morbidity and mortality. Traditionally, capnography has been
      used to confirm the placement of the endotracheal tube. This review looks into
      the literature for an update on the use of capnography in the spontaneously
      breathing patient. RECENT FINDINGS: Several studies support the additional safety
      afforded by the use of capnography in patients undergoing sedation for procedures
      in various situations outside the operating room. Capnography has been used as an
      aid in the diagnosis of pulmonary embolism and sleep-related disorders, as a
      continuous monitor of metabolic status of pediatric patients with diabetic
      ketoacidosis and, along with pulse oximetry, in lung-function laboratories to
      estimate blood gases. SUMMARY: Capnography has become a mandatory or recommended
      monitoring tool in the practice of anesthesiology. It is making inroads into
      other medical specialties as a monitoring and diagnostic tool. The use of this
      technology by non-anesthesiologists will continue to increase. In the opinion of
      the authors capnography should be used in all cases requiring sedation either in
      or out of the operating room.

PMID- 17031089
TI  - Cutaneous carbon dioxide monitoring in adults.
AB  - PURPOSE OF REVIEW: Arterial blood gas analysis is the 'gold standard' method to
      measure the arterial partial pressure of carbon dioxide (PaCO2). However,
      arterial sampling including arterial catheterization is invasive and expensive.
      Cutaneous carbon dioxide tension (PcCO2) measurement is used as a noninvasive
      surrogate measure of PaCO2, which is used to either estimate PaCO2 or determine
      trend changes in the measurement. There has been considerable progress in the
      technical aspects of PcCO2 monitoring in the last few years. In this article, we
      evaluate recent developments and the renewed interest in the subject of PcCO2
      monitoring in adults and discuss the technical aspects, clinical applications and
      the future outlook for this technique in the clinical setting. RECENT FINDINGS:
      With evolution in technology, PcCO2 monitoring is now less cumbersome than
      before. Combined PcCO2 measurement and pulse oximetry is now possible with a
      single earlobe sensor. SUMMARY: The clinical settings in which PcCO2 monitoring
      can be applied include patient monitoring during and after anaesthesia, patients
      receiving noninvasive ventilation, post extubation, endoscopy under sedation, the
      sleep laboratory and the lung function laboratory. Although there is an overlap
      of the clinical indications when both PcCO2 and end-tidal carbon dioxide
      monitoring may be used, it is our opinion that both these methods have
      independent indications and are sometimes also complementary to each other in
      patient care.

PMID- 17031090
TI  - Bibliography current world literature.

PMID- 17031091
TI  - Pride and prejudice: inflammatory bowel disease models and drug development.

PMID- 17031092
TI  - Genomics and inflammatory bowel disease.
AB  - Genomic technologies offer new approaches to the investigation of etiology and
      pathophysiology of inflammatory bowel disease (IBD). Several areas of application
      for these new technologies are possible. One such application is the search for
      gene variations predisposing to the development of the disorder in multiply
      affected families. Genome-wide linkage studies have defined replicated
      susceptibility regions for IBD on chromosomes 6, 12, and 16. These susceptibility
      regions are still very large and each contain several hundred positional
      candidate genes. Efforts are under way at several centers to define the
      underlying molecular variants using systematic linkage disequilibrium and
      candidate gene methods. The pharmacogenetic investigation of gene variations may
      predict response to certain medications to target these therapeutic interventions
      more precisely. The use of global gene expression technologies may allow the
      identification of new pathways or molecules in the inflammatory process. This
      seems to be especially relevant because currently only approximately 8,000 of the
      estimated 100,000 human genes are characterized. In summary, genomic
      methodologies will profoundly influence the progress of IBD research and may lead
      to novel insights into both etiology and pathophysiology of chronic intestinal
      inflammation.

PMID- 17031093
TI  - Immunology of inflammatory bowel disease.
AB  - The immunology of inflammatory bowel disease continues to be an intense area of
      investigation for clues to the pathogenesis of Crohn disease and ulcerative
      colitis. As typical with complex diseases, inflammatory bowel disease research is
      continuously evolving. Without abandoning traditional areas of study, such as
      humoral and cellular immunity and cytokines, investigation is broadening to
      explore new molecules and biologic phenomena. Novel cytokines and cell adhesion
      molecules appear to be involved in inflammation, while the role of nitric oxide
      is being clarified. Leukocyte resistance to apoptosis appears to be a major
      contributing factor to Crohn disease. Epithelial cell-derived defensins and
      receptors are arising as key molecules mediating the interaction of innate and
      acquired mucosal immunity with the enteric flora, and explaining how the latter
      participates in gut inflammation. The results of these combined studies are
      opening novel therapeutic horizons whose implementation offers better forms of
      treatment.

PMID- 17031094
TI  - Discovering the cause of inflammatory bowel disease: lessons from animal models.
AB  - The precise cause of inflammatory bowel disease remains unclear. Relevant animal
      models are important tools for studying the underlying mechanisms of inflammation
      and disease pathogenesis. The purpose of this review is to summarize the various
      types of animal models available for use in inflammatory bowel disease research
      and to illustrate how these models have contributed to a better understanding of
      the etiopathogenesis of inflammatory bowel disease, particularly focusing on
      papers published during calendar year 1999. Studies using appropriate animal
      models have provided important discoveries in this field of investigation. These
      include determination of the key role that pathogenic and regulatory T cells,
      proinflammatory and immunoregulatory cytokines, indigenous bacterial flora, and
      putative predisposing genes play in the disease process. The availability of new
      animal models that closely resemble the human disease is expected to allow
      further characterization of the initiating event(s) in inflammatory bowel disease
      and lead to a possible cure for this devastating disease.

PMID- 17031095
TI  - Therapy for Crohn disease.
AB  - Medical therapy for Crohn disease has advanced incrementally: Small, non
      definitive controlled trials of mesalamine continue to be reported, but the
      results are not sufficient to change the conclusion of a large meta-analysis that
      shows only marginal benefit of mesalamine in Crohn disease. Low-dose, controlled
      ileal-release budesonide is not effective for preventing postoperative recurrence
      of Crohn disease. A loading dose of intravenous azathioprine does not accelerate
      the time to response in patients with steroid-treated Crohn disease; however,
      standard azathioprine may work more quickly than previously reported.
      Mycophenolate mofetil may be therapeutically equivalent to azathioprine for
      active Crohn disease. There is a trend toward benefit of oral methotrexate (15
      mg/wk) for active Crohn disease, and there is no significant difference in the
      blood concentrations of methotrexate in patients with inflammatory bowel disease
      who receive methotrexate (15 or 25 mg weekly) administered subcutaneously.
      Results in a pilot study suggest that tacrolimus may close perianal fistulas in
      patients with Crohn disease. The anti-tumor necrosis factor antibody infliximab
      is effective in closing perianal and enterocutaneous fistulas and in maintaining
      remission in patients with Crohn disease. Infliximab also leads to endoscopic and
      histologic remission. There is a trend toward benefit of subcutaneous recombinant
      interleukin-11 for active Crohn disease. Two pilot studies have shown that
      thalidomide may be of benefit in patients with refractory Crohn disease.

PMID- 17031096
TI  - Medical therapy for ulcerative colitis.
AB  - Last year was not a banner year for developments in medical therapy for
      ulcerative colitis. In contrast to the expansion of therapies for Crohn disease,
      treatment for ulcerative colitis was evolutionary, at best, leading many patients
      to seek alternative medical approaches. Nevertheless, there have been advances in
      the application of aminosalicylates and immune modifiers for ulcerative colitis.
      Additional, nonconventional approaches include nicotine, probiotics, dietary
      therapies, and heparins. Several novel approaches have arisen from animal models,
      including additional means of inhibiting nuclear factor-kappaB and targeting of
      tumor necrosis factor-alpha.

PMID- 17031097
TI  - Clinical features of inflammatory bowel disease.
AB  - The purpose of this review is to highlight new developments during the past year
      regarding diagnosis and clinical features of inflammatory bowel disease.
      Endoscopy remains the cornerstone for diagnosis and evaluation of ileocolonic
      inflammatory bowel disease. In ulcerative colitis, recent studies have challenged
      the concept of a continuous and homogeneous inflammatory process with constant
      rectal involvement: patchy inflammation and rectal sparing were reported in
      treated ulcerative colitis, and frequent cecum and appendiceal orifice skip
      lesions were confirmed. Cross-sectional imaging techniques usefully complement
      endoscopy by assessing whole-bowel thickness and detecting abscesses and
      fistulae. Furthermore, echo Doppler ultrasound is able to measure mesenteric
      blood flow, which is increased in active inflammatory bowel disease and seems to
      parallel inflammatory disease activity. Osteopenia, which affects approximately
      half of patients with inflammatory bowel disease, can be detected by dual-energy
      x-ray absorptiometry and prevented. Hyperhomocysteinemia, a predisposing factor
      for thrombosis, seems to be more frequent in inflammatory bowel disease, and can
      be corrected by folate supplementation. The concept of an aggressive, penetrating
      form of Crohn disease with early postoperative recurrence as opposed to a more
      indolent, nonpenetrating form of the disease, with later recurrence, was recently
      challenged. The most significant predictor of the risk of malignancy in
      inflammatory bowel disease remains the presence of dysplasia in colonic biopsy
      specimens. A dysplastic polypoid lesion or mass is a strong predictor of cancer
      but should be distinguished from the dysplasia inherent in a coincident sporadic
      adenoma.

PMID- 17031098
TI  - Diagnostic markers of inflammatory bowel disease.
AB  - The diagnosis of inflammatory bowel disease is usually straightforward, based on
      a detailed history and physical examination, along with standard radiographic and
      endoscopic investigations, biopsies, and laboratory parameters. More challenging
      is the search for clinically useful, noninvasive markers for Crohn disease and
      ulcerative colitis to accurately screen cases with nonspecific and indolent
      symptoms. Equally required are diagnostic markers that discriminate between these
      two disorders in cases with indeterminate colitis. Another dilemma for clinicians
      is that there are no simple measures to observe disease activity and predict
      relapses. This review describes the recent advances in diagnostic markers that
      afford the ability to screen for inflammatory bowel disease, discriminate between
      its types, and monitor disease activity. These include serological, fecal, and
      tissue markers; permeability tests; and diagnostic imaging using color Doppler
      ultrasonography.

PMID- 17031099
TI  - Atypical forms of inflammatory bowel disease: microscopic colitis and pouchitis.
AB  - Three atypical colitides (and enterides) are collagenous colitis, lymphocytic
      colitis, and ileal pouchitis. Collagenous and lymphocytic colitis are similar
      inflammatory bowel disorders of unknown cause with symptoms including chronic
      watery diarrhea, occurring in middle age. Pouchitis is the most significant long
      term complication in patients with ileoanal pouch anastomosis. The clinical and
      histologic features and management of these entities are discussed.

PMID- 17031100
TI  - Esophageal disorders.

PMID- 17031101
TI  - Gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a common chronic disorder affecting
      millions of people worldwide. This is a review of a number of published studies
      in the past year that increase current understanding or raise important issues
      about this disorder. Among the areas covered are the epidemiology and role of
      genetics in GERD; its pathogenesis with respect to duodenogastric reflux and
      impaired epithelial barrier function; the effects of atropine on transient lower
      esophageal sphincter relaxations; the role of acid suppression, heat shock
      proteins, and the enzyme cyclooxygenase-2 in Barrett esophagus and esophageal
      adenocarcinoma; the complication rates in laparoscopic fundoplication; and the
      results of ablation therapy for the treatment of Barrett esophagus and esophageal
      adenocarcinoma. These investigations reinforce a sense of the complexity of GERD
      and provide optimism that modern technology will continue to be used to develop
      more effective treatments.

PMID- 17031102
TI  - Esophageal motor disorders.
AB  - Motor dysfunction is responsible for symptomatic illnesses both in the proximal
      skeletal muscle region and in the distal smooth muscle esophagus. Practical
      methods for diagnosing and treating oropharyngeal dysphagia continue to reach
      consensus. Achalasia, the most significant of the distal motor disorders, is of
      investigative interest because of the expanded armamentarium of treatment
      options. Minimally invasive surgical methods have taken an important foothold as
      a primary treatment of this disorder. Appreciation is growing for sensory
      dysfunction that accompanies distal motor disorders. Such dysfunction may help
      explain the observed discrepancies between symptoms and measurable motility
      abnormality.

PMID- 17031103
TI  - Chest pain of esophageal origin.
AB  - Patients with unexplained chest pain remain a difficult and perplexing challenge
      for the gastroenterologist. Despite exclusion of a cardiac origin many patients
      remain disabled by pain. In these, a diligent search for an esophageal cause
      gastroesophageal reflux disease, motility abnormalities, or esophageal
      hypersensitivity using all available diagnostic (therapeutic) tools-results in a
      positive outcome. Appropriate use of a diagnostic trial of therapy, ambulatory pH
      monitoring and/or esophageal manometry, necessitates understanding of the
      respective benefits. The recent literature examines the value of a short course
      of high-dose proton pump inhibitors in establishing a diagnosis of
      gastroesophageal reflux disease-associated chest pain, the use of tricyclic
      antidepressants, and behavioral therapy in the management of these difficult
      patients with nonreflux, noncardiac chest pain.

PMID- 17031104
TI  - Barrett esophagus.
AB  - Barrett esophagus continues to intrigue investigators and clinicians alike as the
      new millennium begins. A large number of publications in the past year have
      discussed issues of epidemiology, prevalence, detection, and treatment of Barrett
      esophagus. Chronic symptoms of gastroesophageal reflux were identified as a
      strong risk for esophageal adenocarcinoma. The relative frequency of short and
      long Barrett and cardia intestinal metaplasia in patients who undergo upper
      endoscopy have been better defined. Biomarkers in patients with Barrett may
      eventually be helpful in identifying those at high risk for the development of
      neoplasia. High-dose proton pump inhibition to the point of near elimination of
      esophageal acid exposure remains disappointing in its impact on the surface area
      of Barrett. Finally, the developments in endoscopic therapy for patients with
      Barrett esophagus continue to be promising.

PMID- 17031105
TI  - Endoscopic therapeutic esophageal interventions.
AB  - At the close of the 20th century, therapeutic endoscopy in the esophagus has
      expanded to encompass a broad array of interventions. As the number of procedures
      grows, emphasis in the medical literature has begun to shift to analyses of which
      procedures should be performed. Many studies published in 1999 on topics ranging
      from endoscopic treatment of benign and malignant strictures, to variceal
      bleeding, to Barrett esophagus have focused on which of several methods provides
      the best long-term response with the fewest interventions. This is a review of
      the major published studies of endoscopic interventions in the esophagus as well
      as selected abstracts. The conclusions of these studies and reports of new
      endoscopic therapies draw a clear map of where nonoperative esophageal
      therapeutics are headed in the next several years.

PMID- 17031106
TI  - Esophageal cancer.
AB  - Papers published in the English literature on esophageal cancer in 1999 were
      retrieved by a MEDLINE search. Selective publications were reviewed in light of
      current knowledge. Many studies were performed to refine staging methods of
      esophageal cancer, especially in the use of endoscopic ultrasound. Although
      better designs have overcome the problem of nontraversable tumors, its use in
      staging after neoadjuvant therapies remains suboptimal. Important studies on
      various surgical techniques were reported, including randomized trials on
      different routes of reconstruction after esophageal extirpation, and the updated
      results of transhiatal resections. In contrast to the minimalist approach of
      transhiatal resection, investigators from both East and West have also described
      the pathologic basis of lymphatic spread of esophageal cancer and its
      implications, favoring more radical lymphadenectomy. Another avenue that was
      explored is the use of neoadjuvant therapies to improve outcome. Different
      regimens were studied, and many papers focused on the molecular prediction of
      favorable response to such therapies. Overenthusiastic adoption of multimodality
      treatments is cautioned, however, in that they have not been validated. Further
      work is much needed in this area of research.

PMID- 17031107
TI  - Surgery, radiotherapy, and chemotherapy in carcinoma of the esophagus.
AB  - Esophageal carcinoma remains a highly lethal disease that has shown a recent
      profound increase in prevalence and an equally dramatic epidemiologic shift.
      There is a well recognized causal association between gastroesophageal reflux
      disease and adenocarcinoma of the esophagus, and the molecular events underlying
      this progression from mucosal injury, to metaplasia, to dysplasia, to carcinoma
      are now becoming clear. Current diagnostic modalities and preoperative staging
      systems all have significant limitations. Fortunately, chemoprevention strategies
      and the identification of clinically useful molecular biomarkers that may be used
      to stage disease and select appropriate therapy are on the horizon. The extent of
      surgical resection for esophageal carcinoma remains an area of great controversy.
      Disease that is confined to the mucosa is being diagnosed more commonly, and
      endoscopic ablative techniques have been proposed. To date, however, preoperative
      discrimination of tumor depth and presence of regional nodal metastases remains
      inadequate in these very early lesions, and caution is urged before adopting
      therapies that may compromise cure. For disease penetrating the mucosa, the
      extent of surgical therapy must be tailored by the objectives of treatment (cure
      vs palliation) and preoperative stage. Surgical resection is the current standard
      of care, with combined-modality therapy reserved for prohibitive surgical
      candidates. No clear survival benefit has been documented for neoadjuvant
      radiotherapy or chemotherapy alone. The results of preoperative combined-modality
      therapy, including three prospective, randomized trials, are encouraging but to
      date have not shown a definite benefit.

PMID- 17031108
TI  - Bibliography current world literature.

PMID- 17031110
TI  - Signal transduction in pancreatic acinar cell physiology and pathophysiology.
AB  - The pancreatic acinar cell is a valuable cell model for understanding how
      activation of plasma membrane receptors generates signals that propagate,
      amplify, diversify, and integrate to control cellular function. A primary
      signaling system involves the activation of heterotrimeric G proteins that
      stimulate phospholipases, leading to the generation of phospholipid messengers. A
      major action of the phospholipid messengers is the control of cytoplasmic Ca(2+)
      levels. The complex mechanisms involved in controlling the initiation, form, and
      spatial pattern of Ca(2+) release are being revealed in increasing detail and
      complexity. The connections between the signaling networks and the final events
      of secretion are beginning to be revealed. Advances have also been made in
      understanding the processes that underlie the pathologic effects of receptor
      overactivation.

PMID- 17031111
TI  - Acute pancreatitis.
AB  - Acute pancreatitis is a process that continues to interest physicians and
      research scientists. Understanding potential factors initiating acute
      pancreatitis, mechanisms regulating the local and distant inflammatory response,
      methods for accurately predicting outcome, and possible therapeutic interventions
      continue to be investigated. Current interest in inflammatory response of the
      acute injury focuses on proinflammatory and anti-inflammatory cytokines as
      markers for disease severity and predictors of outcome. Recent studies confirm
      the utility of physical examination and existing markers such as C-reactive
      protein and interleukin-6 in predicting the severity of acute pancreatitis.
      Understanding the molecular mechanism of lung injury remains a major focus for
      future therapeutic targets, since pancreatitis-associated pulmonary injury
      results in significant morbidity and is a major indication for intensive care
      unit admissions.

PMID- 17031112
TI  - Chronic pancreatitis.
AB  - In the past year, there has been at least one important clinical paper that sheds
      light on the character and natural history of painful chronic pancreatitis, which
      has important clinical implications. In addition, several novel mutations have
      been described in the cationic trypsinogen gene in patients with hereditary
      pancreatitis. The mechanism by which these mutations cause pancreatic disease
      remains speculative. The diagnosis of early chronic pancreatitis is
      controversial. A novel noninvasive pancreatic function test (measurement of
      postprandial APOB-48) was reported but is unlikely to be a sensitive test of
      pancreatic function. Pancreatic fibrosis is frequently seen in alcoholics without
      chronic pancreatitis, and this makes it difficult to interpret the findings on
      endoscopic ultrasonogram. Recent studies highlight the difficulty in abolishing
      pancreatic steatorrhea. Recently fibrosing colonopathy in adult patients has been
      reported. Extracorporeal shockwave lithotripsy combined with endoscopic therapy
      failed to benefit patients with calcific chronic pancreatitis.

PMID- 17031113
TI  - Molecular genetics of ductal pancreatic neoplasia.
AB  - The molecular genetic profiles that characterize pancreatic ductal neoplasia have
      taken shape recently with the help of immunohistochemistry and the establishment
      of the nomenclature describing pancreatic ductal tumorigenesis. K-ras mutations
      frequently occur early, changes in the expression and genetic integrity of the
      p16 gene appear in intermediate lesions, and the inactivation of the p53, DPC4,
      and BRCA2 genes occur late in the neoplastic progression. Tumor-suppressor genes
      inactivated in pancreatic cancer such as ALK5, TGFBR2, MKK4, and STK11/LKB1 have
      been identified, although their roles in tumor progression are not yet well
      defined. Additional discoveries in this tumor system may be on the horizon, will
      further refine the molecular genetic profiles for the disease, and should suggest
      some clinical uses for this fund of knowledge.

PMID- 17031114
TI  - Pancreatic surgery.
AB  - Several important advances in pancreatic surgery have been made over the past
      year. As in other areas of general surgery, laparoscopic techniques are being
      used with increasing frequency, but their real value remains to be determined.
      Methods to stage pancreatic cancer, perform palliative bypass, relieve pain, and
      perform distal pancreatic resections have been described. Using more conventional
      surgical approaches, data continue to accumulate about pylorus preserving
      pancreaticoduodenectomy as an alternative to the standard operation. The survival
      benefit of extended pancreatic resection for pancreatic cancer remains dubious.
      Studies continue to demonstrate lower morbidity and mortality rates for
      pancreaticoduodenectomy performed at high-volume centers. In the arena of chronic
      pancreatitis, pain relief is still the most common reason for surgical treatment,
      and the efficacy of various operations has been assessed by some new studies.
      Data continue to show that aggressive surgical treatment for infected necrosis
      leads to improved survival in patients with severe acute pancreatitis.

PMID- 17031116
TI  - Biliary tract physiology.
AB  - Cholangiocytes, the cells lining the bile ducts, are now recognized as important
      contributors to and modulators of bile formation. During the last few years,
      remarkable insights have been made into the mechanisms of fluid, electrolyte, and
      solute transport by biliary epithelia, as well as increasing knowledge of the
      complex endocrine, paracrine, and neurologic factors regulating bile formation.
      Advances in the past year include an increased understanding of the interaction
      between bile acids and cholangiocytes in the regulation of bile formation in
      normal and cholestatic states and greater insight into the pathogenic mechanisms
      of biliary diseases. References to recent comprehensive reviews of specific areas
      of biliary physiology are provided, and new experimental models are also
      described.

PMID- 17031117
TI  - Biliary tract cancer.
AB  - Investigation into the molecular and cellular biology of carcinogenesis continues
      to elucidate potential mechanisms for the initiation and progression of biliary
      tract cancer. The potential role of cell cycle regulators, such as Fas ligand,
      has been examined in the etiology of bile duct carcinoma. In addition, there is
      evidence for a possible link between chronic inflammation and malignant
      transformation through the relation between nitric oxide and DNA repair enzymes.
      Noninvasive imaging modalities, including helical computed tomography scanning,
      magnetic resonance cholangiopancreatography (MRCP) and positron emission
      tomography (PET) scanning, are gaining acceptance and may eventually supplant
      standard methods of evaluation. In addition, innovative tissue-sampling
      modalities including choledochoscopy are being developed. Several large series,
      Japanese and Western, continue to report improved 5-year survival rates after
      aggressive surgical resections of hilar cholangiocarcinoma. Although
      chemotherapeutic options remain limited in biliary tract carcinoma, radiation
      therapy may provide a benefit in local control in patients with microscopically
      positive margins. Photodynamic and multimodality therapy also may become
      important components of improving palliation for patients with advanced disease.

PMID- 17031118
TI  - Sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown
      etiology. Immunogenetic factors are considered important in its pathogenesis. The
      genetic susceptibility to primary sclerosing cholangitis is associated, in part,
      with the HLA HLA-DRB1, DQA1, DQB1 haplotype. Liver histology in primary
      sclerosing cholangitis is characterized by a portal inflammatory infiltrate
      mostly composed of memory T cells. Many patients eventually will develop
      cholangiocarcinoma, and inactivation of the p16 tumor-suppressor gene might be
      involved in neoplastic transformation. Alcohol consumption might be a risk factor
      for cholangiocarcinoma, and, in some patients, elevation of serum CA19-9 marks
      the neoplastic transformation. To date, no medical treatment has been proven
      effective. Endoscopic therapy might be useful in some patients, but controlled
      studies are lacking. Liver transplantation remains the only effective treatment.
      Posttransplant survival and quality of life are continuously improving despite
      the fact that the disease may recur in some patients after transplantation.
      Nevertheless, patient selection and timing of indication for liver
      transplantation remain uncertain.

PMID- 17031119
TI  - Gallstones.
AB  - At the turn of the millennium, significant advances continue to be made into the
      epidemiology and pathophysiology of gallstone disease. The NHANES III study, the
      largest American population-based study of gallstone disease, estimated that more
      than 20 million Americans have undergone gallbladder surgery or currently have
      gallstones. Insulin resistance may be an independent risk factor for gallstone
      disease.Cholecystokinin receptors may be responsible for the altered motility of
      the gallbladder smooth muscle, and mucin may play an underestimated role as a
      pronucleating factor. For the first time, researchers have been able to directly
      observe cholesterol crystallization in human bile. Improved understanding of the
      multiple factors involved in the pathogenesis of gallstone disease should lead to
      new therapeutic and preventive strategies.

PMID- 17031121
TI  - Bibliography current world literature.

PMID- 17031120
TI  - Endoscopic management of biliary disease.
AB  - Endoscopic management of biliary disease remains at the forefront of minimally
      invasive means of providing therapy, as well as contributing important diagnostic
      information in complex clinical scenarios. The authors review recent advances and
      reported trials of therapy and revisit important controversial issues. The
      management and diagnosis of choledocholithiasis are discussed, as well as
      endoscopic techniques for attaining biliary access at endoscopic retrograde
      cholangiopancreatography. In addition, management of biliary anastomotic
      strictures in liver transplant patients, role of cholangioscopy, and recent
      advances in stent technology are reviewed.

PMID- 17031122
TI  - Stomach and duodenum.

PMID- 17031123
TI  - Gastric secretion.
AB  - This article summarizes data published during the past year that improve our
      understanding of the mechanisms by which various neurotransmitters, paracrine
      agents, and hormones regulate gastric acid secretion and are themselves
      regulated. The main stimulants of acid secretion are histamine, gastrin, and
      acetylcholine. The main inhibitor is somatostatin, which exerts a tonic restraint
      on parietal, enterochromaffin-like (ECL), and gastrin cells. Histamine, released
      from ECL cells, stimulates the parietal cell directly via H(2) receptors and
      indirectly via H(3) receptors coupled to inhibition of somatostatin secretion.
      Gastrin, acting via gastrin/cholecystokinin-B (CCK-B), now termed CCK(2),
      receptors on ECL cells activates histidine decarboxylase, releases histamine, and
      induces ECL hypertrophy and hyperplasia. The latter might be responsible for the
      rebound hyperacidity observed after withdrawal of long-term antisecretory
      therapy. The neurotransmitter pituitary adenylate cyclase-activating polypeptide
      stimulates histamine secretion from isolated ECL cells, but its physiologic role,
      if any, is not known. Acetylcholine, released from gastric postganglionic
      intramural neurons, stimulates the parietal cell directly via muscarinic M(3)
      receptors and indirectly by inhibiting somatostatin secretion. Although infection
      with H. pylori is associated with increased basal and stimulated acid outputs in
      patients with duodenal ulcer, most people infected with the organism are
      asymptomatic and have pangastritis with decreased acid output. In the latter,
      eradication of the bacterium leads to an increase in gastric acidity and is
      associated with a two-to threefold increase in gastroesophageal reflux.

PMID- 17031124
TI  - Gastroduodenal mucosal defense.
AB  - The gastroduodenal mucosa is a model system of defense with several structural
      levels and biologic strategies that are closely interrelated with each other to
      cope with the harmful ingredients of ingested food and the potentially
      deleterious effects of gastric acid and pepsin. Experimental and clinical
      research carried out during the review period added to the understanding of each
      component of the multiple mechanisms of gastroduodenal mucosal protection. In the
      first place, mucosal integrity is defended by the mucus gel barrier, the
      epithelial cell barrier, and the immune barrier. The properties of these barriers
      are maintained by adequate regulation of mucus production, bicarbonate secretion,
      mucosal microcirculation, and motor activity. These regulatory systems are
      alarmed by nociceptive neurons and the mucosal immune system which includes
      chemokine-secreting epithelial cells. The ultimate defense system is rapid repair
      of the injured mucosa under the control of several growth factors. Progressing
      insight into the network of mucosal defense not only will improve existing
      therapies of inflammation and ulceration but also will provide new leads for the
      management of functional diseases in the gastroduodenal region.

PMID- 17031125
TI  - Gastroduodenal motility.
AB  - During the past year there were significant developments in the area of
      gastroduodenal motility--in basic physiology, pathophysiology, diagnosis, and
      therapy. Some represented a major breakthrough; most were incremental. Evidence
      continues to accumulate to support an important role for the stomach in the
      regulation of food intake, and the physiologic mechanisms involved continue to be
      revealed. Although there were no dramatic developments in the area of diagnostic
      methodology, several studies sought to refine or to extend the use of currently
      available techniques. Gastric motor activity and that of the proximal stomach
      continue to attract attention in dyspepsia and gastroesophageal reflux disease,
      and the range of disorders that may disrupt the motor function of the stomach
      continues to extend. On the therapeutic front, advances were largely in refining
      the indications and the uses of available therapies, rather than in the
      development of novel agents.

PMID- 17031126
TI  - The treatment of peptic ulcer disease.
AB  - There is a continuation of the debate on the management of dyspepsia while the
      role of Helicobacter pylori in duodenal ulcer disease is being questioned with
      renewed vigor, specifically in the United States. The interaction of NSAIDs and
      H. pylori provided some interesting, if at times confusing, literature while the
      debate on the safety of long-term acid suppression remained unresolved. There
      were some interesting developments with regard to therapeutic agents during this
      period. A fourth proton pump inhibitor was introduced to the market while
      cisapride, a drug previously considered safe, was effectively withdrawn from the
      North American market because of safety concerns. More data on the COX-1-sparing
      agents became available, and their impressive gastrointestinal safety profile was
      confirmed. It was noted, however, that the incidence of dyspepsia, experienced by
      users of these drugs, may remain a problem.

PMID- 17031127
TI  - NSAID gastrointestinal toxicity.
AB  - Toxic effects in the upper gastrointestinal tract, primarily complicated gastric
      and intestinal ulcers, are the most common undesirable effects of the
      nonsteroidal antiinflammatory drugs (NSAIDs). During the last several years there
      have been several advances, both in the laboratory and clinically, toward
      reducing NSAIDs' gastrointestinal toxicity. Some of these important developments
      have been the delineation of mechanisms of NSAID-induced GI toxicity,
      identification of groups at highest risk for development of NSAID-induced
      gastrointestinal complications, recognition of co-therapies that could reduce
      NSAID toxicity, and, most recently, development of classes of NSAIDs that have an
      improved gastrointestinal safety profile. Many of these advances occurred during
      the last year. This review focuses on several of the important recent
      observations that have improved our understanding and the safety of NSAIDs in the
      gastrointestinal tract.

PMID- 17031128
TI  - Nonulcer dyspepsia.
AB  - New definitions of functional disorders in general and nonulcer dyspepsia in
      particular were published in the period of review. Although the definition of
      functional dyspepsia as persistent or recurrent unexplained upper abdominal pain
      or discomfort stayed essentially the same, new definitions of dyspepsia subgroups
      were introduced based on the predominant symptom; a reflux-like dyspepsia
      subgroup was not supported. It is hoped that these criteria, derived by a
      consensus among international experts in the field, will improve the reliability
      and the interpretability of future epidemiologic and interventional studies. A
      wide range of studies dealt with the role of putative etiological factors in
      functional bowel disorders including Helicobacter pylori, altered visceral
      sensation, or upper intestinal motility. Although eradication of H. pylori does
      not seem to relieve dyspepsia over placebo in recent studies of nonulcer
      dyspepsia, eradication of H. pylori has generally been advised because of
      suspected beneficial long-term effects (eg, treatment of misdiagnosed ulcer
      disease) that probably overweigh the potential risks.

PMID- 17031129
TI  - Interventional procedures.
AB  - During the past year, numerous articles were published on interventional
      procedures of the stomach, focusing on upper gastrointestinal tract bleeding,
      gastric cancer, gastric outlet obstruction, and benign disease. In the area of
      upper gastrointestinal tract bleeding, early endoscopy is warranted for early
      therapeutic intervention and for triage. In patients with bleeding related to
      peptic ulcer disease, combination therapy (epinephrine injection in conjunction
      with electrocoagulation therapy) remains the standard of care. Hemoclipping is a
      new technique that may be helpful in cases in which conventional therapy fails.
      Repeat endoscopy should always be considered in patients in whom the first
      attempt at endoscopic therapy fails. In patients with bleeding related to portal
      hypertension, prophylactic antibiotics may decrease the risk of infections.
      Banding remains the therapy of choice for this group of patients. There is no
      documented benefit for combination therapy (banding and sclerotherapy).
      Transjugular intrahepatic portosystemic shunts may be helpful in the treatment of
      hypertensive portal gastropathy but not gastric vascular ectasias. In the area of
      gastric cancer, management revolves around staging. This can be accomplished best
      through the use of CT scan and endoscopic ultrasound. In patients with early
      limited disease, attempt at endoscopic mucosal resection should be considered.
      This technique can be performed in a variety of ways: the most common method
      seems to be through the use of a saline injection, to separate the mucosa
      submucosal layer, followed by a cap-assisted snare resection with suction. The
      safety, efficacy, and outcome of this technique are reviewed. Gastric outlet
      obstruction remains a difficult problem to treat endoscopically. However, there
      is some evidence that endoscopic therapy may be successful in benign disease and
      should be considered prior to surgical intervention.

PMID- 17031130
TI  - Gastric cancer.
AB  - Gastric adenocarcinoma is the most common malignancy of the upper
      gastrointestinal tract. During the past two decades it has migrated toward the
      gastroesophageal junction. Gastroesophageal reflux and obesity may play a role.
      Recent research suggests that a number of biologic and molecular differences
      exist in patients with gastric cancer. Further investigation in these areas may
      help in predicting outcome and directing therapy. Gastric cancer is not a curable
      condition when metastases are present. However, postoperative chemotherapy plus
      chemoradiotherapy, in the Intergroup trial 0116, prolonged the overall and
      disease-free survival rates of patients after a curative (R0) resection. It
      should be considered the new standard of care in patients with gastric cancer who
      have undergone curative resection with stage Ib-IV disease. Preoperative therapy
      strategies may increase the likelihood of R0 resection and remain an area of
      active investigation. Finally, development of more active agents is needed for
      the treatment of metastatic tumors.

PMID- 17031131
TI  - Gastroduodenal disorders in children.
AB  - Studies within the past year examining the mechanisms underlying infantile
      hypertrophic stenosis at the cellular and molecular level are reviewed. A number
      of new modalities, including electrogastrography, and the 13C octanoid acid
      breath test have been used in the study of normal and abnormal gastrointestinal
      motility, as well as for the characterization of patterns of development of
      gastric motility in early infancy. Several studies pertaining to the natural
      outcome, the mode of transmission, and the associated symptomatology of
      Helicobacter pylori were published, attesting that, despite the tremendous
      progress achieved in our understanding of H. pylori, important gaps remain in our
      knowledge of this microorganism. Newly described clinical presentations of
      eosinophilic gastroenteritis and food allergy will also be of interest to the
      reader.

PMID- 17031133
TI  - Epithelial cell antigen presentation.
AB  - For decades intestinal epithelial cells were thought of as passive barriers to
      luminal contents, cells involved in nutrient absorption and electrolyte
      secretion. Studies during the past 10 to 15 years have changed that concept as
      our understanding of mucosal immunity has evolved and as we have come to
      understand that the regulation of this system is unique in terms of cellular
      interactions and factors produced. The intestinal epithelial cell has moved to
      the forefront of these studies where it has been shown to be an active
      participant in mucosal immunoregulation and inflammation. Results of the earliest
      studies suggested that epithelial cells might be involved in immune regulation
      because they expressed a series of cell surface molecules that correlate with
      classical antigen presentation (class I and II MHC molecules). Later on, the
      expression of nonclassical class I molecules was identified on these cells as
      well, raising the possibility of novel forms of interactions with unique cell
      populations. This was followed by the observation that epithelial cells secrete
      cytokines and chemokines, which not only regulate mucosal immune responses but
      also regulate inflammatory responses. By such processes, the IEC has been
      proposed as being a bridge between innate and adaptive immunity. The recent
      description of Toll-like receptors on IECs adds further support to this concept.
      Clearly there is growing appreciation of the multifaceted role that the IEC plays
      in the gut. The work on IECs in the past year has helped to refine this role.

PMID- 17031134
TI  - The role of neuroenteric hormones in intestinal infectious diseases.
AB  - It is now well established that communication among the enteric nerves, hormones,
      and neuropeptides plays a role in the pathogenesis of infectious gastrointestinal
      conditions. The results of several studies suggest that enteric nerves and
      hormones modulate important gastrointestinal functions such as intestinal
      motility and transport, intestinal permeability, fluid secretion, and
      inflammation in response to infectious agents. During the past year several gut
      brain peptides, including substance P, neurotensin, and galanin, emerged as
      important mediators in the development and progress of intestinal infectious
      conditions. The intestinal mechanism of neuropeptide and hormone action involves
      direct effects via binding to receptors on the intestinal epithelium as well as
      on immune cells localized underneath the epithelial layer. Based on the available
      evidence from whole animal models it is possible that these new paradigms may
      offer novel therapeutic strategies in the treatment of gastrointestinal
      infections. This review summarizes recent progress on the identification of
      peptide hormones participating in the pathophysiology of infectious intestinal
      conditions and discusses the possible mechanism(s) of action involved in these
      processes.

PMID- 17031135
TI  - Transforming growth factor-beta: an important cytokine in the mucosal immune
      response.
AB  - Cytokines are important mediators in the intestine regulating both oral tolerance
      and mucosal inflammation. Central to this immune-regulatory role is the cytokine
      transforming growth factor-beta (TGF-beta). Oral tolerance and inflammatory
      responses in the gut are regulated through the balance of the Th1, Th2, and Th3
      lymphocyte responses--a balance influenced strongly by TGF-beta. TGF-beta also
      modulates B-cell responses by increasing the production of immunoglobulin A (IgA)
      while decreasing the production of IgG, IgM, and IgE. In intestinal epithelial
      cells, TGF-beta activates signal transduction pathways resulting in the
      inhibition of proliferation and tumorigenesis. Currently, these signaling
      pathways are being dissected at the molecular level.

PMID- 17031136
TI  - Innate immunity and the gut.
AB  - The intestinal epithelium encounters a unique environment consisting of microbes,
      both commensals and pathogens, as well as dietary nutrients and antigens. This
      complex composition necessitates the presence of a dynamic system of defense to
      contain both pathogenic and commensal bacteria within the lumen yet allow for
      nutrient absorption. Tight junctions provide protection of the intercellular
      spaces while other surface molecules, such as intestinal trefoil factor, help to
      maintain the structural integrity of the epithelium. Other more active processes,
      including upregulated expression and activation of antimicrobial peptides and
      enhanced fluid secretion, provide a second level of innate defense. Despite
      providing the interface between an exuberant immune system and a highly antigenic
      lumenal environment, the intestinal epithelium must remain quiescent. As such,
      several novel antiinflammatory mechanisms were recently identified. Studies that
      elaborate the various aspects of these pathways are discussed in this review.

PMID- 17031137
TI  - The immunologic basis for intestinal food allergy.
AB  - There has been considerable recent broadening of basic concepts of intestinal
      food allergy, in particular the importance of non-IgE-mediated mechanisms. The
      traditional emphasis on IgE-mediated allergy now appears inappropriate in light
      of current studies of the basic mechanisms of oral tolerance to dietary antigen
      and of increasing recognition of the requirement for early infectious challenge
      in the prevention of allergic sensitization. This major change in emphasis has
      been forced both by basic scientific studies and by recognition of novel patterns
      of food allergic disease within the pediatric population, in which rapid increase
      in food-allergic sensitization has been noted in the last decade and previously
      rare phenomena such as multiple food allergies and sensitization of exclusively
      breast-fed infants to antigens eaten by the mother have become commonplace. It is
      thus emerging that the possession of exaggerated IgE responses may not be the
      direct cause of food allergic sensitization but may ensure that such
      sensitization is clinically obvious. Those without such immediate responses have
      a complex of symptoms, including diet-responsive eczema and a marked disturbance
      of intestinal motility. The clear demographic links with socioeconomic privilege
      and relative protection from gastrointestinal infarctions concord with recent
      murine data suggesting an obligatory input from innate immune responses to the
      gut flora in the establishment of oral tolerance.

PMID- 17031138
TI  - Immunology of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is known for its ability to establish persistent
      infection and cause chronic hepatitis in most infected individuals. The
      pathogenesis of hepatic injury and the precise mechanisms underlying viral
      persistence are unknown. Accumulating evidence indicates that successful
      elimination of HCV is associated with the induction and maintaining of strong
      helper T-cell and cytotoxic T-cell responses against multiple viral epitopes. In
      contrast, patients who develop chronic HCV infection are characterized by the
      lack of strong viral-specific helper T-cell responses. The failure to mount and
      maintain strong HCV-specific T-cell responses may be determined by the genetics,
      especially the major histocompatibility complex background, of the host. However,
      it is likely that other host and viral factors are also involved in determining
      the outcome of HCV infection. Available data suggest that HCV is not cytopathic
      to hepatocytes and that liver injury associated with chronic HCV infection is
      likely to be mediated by immune responses against HCV-infected hepatocytes. In
      addition to hepatitis, HCV infection may also cause breaching of immune
      tolerance, leading to autoimmune disorders. Although the lack of a small animal
      model and a tissue culture system has impeded research on hepatitis C virus (HCV)
      infection, recent studies in humans and chimpanzees have significantly enhanced
      our understanding of the interaction between HCV and the host's immune system.
      This review focuses on the most recent advances in our understanding of the
      immunology of HCV infection. In particular, the possible mechanisms of how HCV
      establishes chronic infection are discussed. The pathogenesis of liver injury,
      the immunogenetics of HCV infection, and the effect of HCV infection on host's
      immune function are also reviewed.

PMID- 17031139
TI  - New immunologic treatments for inflammatory bowel disease.
AB  - After many years with little progress in new treatments for patients with
      inflammatory bowel disease, there is now rapid expansion of a new class of
      immunologic agents. These agents are designed to disrupt proinflammatory pathways
      at specific sites. Monoclonal antibodies to tumor necrosis factor-alpha (TNF
      alpha) are already transforming the lives of some patients with previously
      intractable Crohn disease, and further TNF-alpha directed therapies are being
      developed. Clinical trials are now underway on agents that inhibit adhesion
      molecules and antiinflammatory cytokines, while attempts are being made to
      actively immunize against TNF-alpha. Promising data continue to be reported,
      although long-term safety data are still mostly unavailable. Although these
      agents are proving to be very effective in the treatment of patients with Crohn
      disease, their use should continue to be restricted while indications and dose
      regimens are defined.

PMID- 17031140
TI  - Bibliography current world literature.

PMID- 17031142
TI  - Bacterial infections: small intestine and colon.
AB  - Bacterial enteric infections exact a heavy toll on human populations,
      particularly among children. Despite the explosion of knowledge on the
      pathogenesis of enteric diseases experienced during the past decade, the number
      of diarrheal episodes and human deaths reported worldwide remains of apocalyptic
      dimensions. However, our better understanding of the pathogenic mechanisms
      involved in the onset of diarrhea is finally leading to preventive interventions,
      such as the development of enteric vaccines, that may have a significant impact
      on the magnitude of this human plague.

PMID- 17031143
TI  - Rotavirus and calicivirus infections of the gastrointestinal tract.
AB  - Virus infections of the gastrointestinal tract, leading to gastroenteritis, are a
      common problem in both developed and developing countries. Rotavirus and Norwalk
      like viruses are the most common agents responsible for clinically severe disease
      in humans, and this paper focuses on new information about the mechanisms of
      pathogenesis and epidemiology of these two pathogens. Rotavirus-induced disease
      involves a viral enterotoxin and activation of the enteric nervous system, as
      well as malabsorption, suggesting that common mechanisms of pathogenesis may
      exist between viral and bacterial pathogens. Each gastrointestinal virus
      possesses unique molecular properties that can be exploited to discover new
      information about responses of cells of the gastrointestinal tract. Work
      continues toward making vaccines for rotavirus and Norwalk-like viruses.

PMID- 17031144
TI  - Emerging and reemerging intestinal protozoa.
AB  - The intestinal protozoa have gained importance to physicians practicing medicine
      in the United States, Canada, and Europe during recent years as a result of
      increasing world travel, the globalization of the world's economy, and the
      growing number of chronically immunosuppressed people. During the spring of 1996,
      Cyclospora cayetanensis caused diarrhea in approximately 1500 people exposed to
      Guatemalan raspberries. This epidemic recurred in 1997, emphasizing the risks of
      the global economy and food supply on which we depend. In addition to importation
      of intestinal protozoa from the tropics, AIDS and the increasing use of organ
      transplants have created a new population of people at risk for chronic infection
      by ubiquitous protozoa previously not known to cause serious human disease. These
      infections include cryptosporidiosis, isosporiasis, and microsporidiosis.
      Finally, Entamoeba histolytica, the etiologic agent of invasive amebiasis, has
      only recently been recognized to be a distinct species from a nonpathogenic but
      indistinguishable (by light microscopy) intestinal commensal, Entamoeba dispar.
      The rapidly changing epidemiology of these intestinal protozoa, as well as new
      approaches to diagnosis and treatment of these protozoa, are discussed.

PMID- 17031145
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Helicobacter pylori infects over half of the world population. Infection with the
      bacterium causes gastritis and peptic ulcer disease and is associated with the
      development of gastric cancers. However, only a small proportion of individuals
      develop these complications of infection. Therefore, identification of both host
      and bacterial factors that mediate disease is an intense area of current research
      interest. This review highlights recent advances in understanding of the
      mechanisms underlying disease pathophysiology following infection with H. pylori.

PMID- 17031146
TI  - Treatment of Helicobacter pylori.
AB  - Helicobacter pylori causes several gastroduodenal diseases. Various antibiotic
      regimens are available that eradicate H. pylori in 80 to 90% of patients, but no
      regimen cures all patients. Dual therapy is now obsolete. Triple therapy with two
      antibiotics and either a proton pump inhibitor or bismuth is the regimens of
      choice. Metronidazole and clarithromycin are the two key antibiotics. Antibiotic
      resistance against these two drugs is becoming more problematic and should be
      taken into consideration when choosing a regimen. Antibiotic resistance is
      usually induced after failure. Quadruple therapy has been used as a salvage
      regimen in failed cases but it is also the most complicated regimen. Several new
      agents are being studied including a single capsule that contains bismuth,
      metronidazole, and tetracycline.

PMID- 17031147
TI  - Gastrointestinal infections in children.
AB  - Gastrointestinal infections in children are a major cause of morbidity and
      mortality worldwide. Children living in developing countries are particularly
      susceptible to infectious diarrhea because of poor standards of hygiene and
      sanitation. Although the magnitude of diarrheal illnesses in developed countries
      is less, costly hospital admissions are still frequent. The causal agent of
      infectious diarrhea is most frequently related to age, geographical location,
      lifestyle habits, use of antibiotics, associated medical conditions, social
      circumstances, and degree of immune competence. In this article we present some
      of the most important articles published in the field during the last year. The
      role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer
      disease has been shown in adults and children. Information about the natural
      history of H. pylori, symptomatology, and diagnostic therapeutic approaches for
      children are being generated constantly; we discuss some of the most relevant
      information in this review.

PMID- 17031148
TI  - Gastrointestinal infections in the immunocompromised host.
AB  - The gastrointestinal tract is a common site of infection in the opportunistic
      host. Pathogens range from highly virulent organisms, which infect people with
      well functioning immune systems as well as people with poorly functioning immune
      systems, to opportunistic organisms, which infect only those with impaired immune
      systems. Viruses, bacteria, fungi, and protozoa lead to disease that can be
      especially severe, debilitating, and difficult to treat in the immunocompromised
      host. Yet in this era of highly active antiretroviral therapy for HIV-infected
      patients and strategies to reduce immunosuppression in transplant and oncology
      patients, appropriate diagnostic tests and treatment can both improve the quality
      of life and decrease mortality. In this article, I review the changing
      pathogenesis, epidemiology, clinical presentation, diagnosis, and treatment of
      gastrointestinal infections in the immunocompromised host.

PMID- 17031149
TI  - Treatment of gastrointestinal infections.
AB  - Studies aimed at improving treatment strategies for patients with acute diarrhea
      have included the clinical testing of modifications to the standard oral
      rehydration solution. A malabsorbed carbohydrate has been found to improve
      resuscitation, probably through the recruitment of colonic absorptive capacity. A
      reduced osmolarity solution is safe in adults and as effective as the standard
      solution. For non-nursing infants, increasing the frequency of feeding with
      reduced volume results in comparable total caloric intake and diminishes the risk
      of prolonged diarrhea. Increasing resistance of important enteric pathogens to
      inexpensive and newer antibiotics continues to be a concern. Reports from Asia of
      decreased Salmonella typhi resistance to chloramphenicol, attributed to
      restricted antibiotic usage, may indicate a reversal of the usual trend. A
      strategy to block the action of shiga toxins in the gut through the use of
      recombinant bacteria has shown promise in a mouse model. A small but well
      designed study supported the use of either norfloxacin or amoxicillin-clavulanic
      acid in the treatment of small bowel overgrowth syndrome. Studies exploring
      passive immunity strategies for the treatment of Escherichia coli,
      Cryptosporidium, and Candida infections have reported variable levels of success.

PMID- 17031150
TI  - Molecular-phylogenetic analyses of human gastrointestinal microbiota.
AB  - Molecular-phylogenetic methods have revolutionized the analysis of complex
      microbial communities. Polymerase chain reaction amplification and phylogenetic
      analysis of small-subunit ribosomal RNA gene sequences allow microbes to be
      identified objectively, even in the absence of cultivation. Furthermore, the
      sequence information obtained by these means can be used to design sequence-based
      tools for identifying, tracking, and diagnosing the presence of microbes in
      complex samples. In this article, we summarize this approach and review its
      application to the study of the human gastrointestinal microbiota. Although just
      beginning, molecular-phylogenetic surveys of human gut microbes have revealed
      that most microbes identified in the gastrointestinal tract represent novel,
      previously undescribed species. A full description of the microbial constituents
      of the human gut will set the groundwork for interpreting how the
      gastrointestinal microbiota influence the health of the host.

PMID- 17031151
TI  - The role of probiotics in the treatment of intestinal infections and
      inflammation.
AB  - Clinical studies have established that certain probiotics are useful in a variety
      of intestinal disorders, including viral diarrhea, antibiotic-associated
      diarrhea, Clostridium difficile-associated diarrhea, and traveler's diarrhea.
      Evolving data suggest that probiotics might be useful in the control of
      inflammatory diseases, treatment and prevention of allergic diseases, cancer
      prevention, and stimulation of the immune system, which may result in the
      reduction in respiratory disease. A review of current data regarding the most
      common probiotics is presented. It is important that probiotic use be directed by
      well-designed, placebo-controlled clinical studies published in peer-reviewed
      journals.

PMID- 17031153
TI  - Nonsteroidal antiinflammatory drugs, cyclooxygenase-2, and colorectal cancer
      prevention.
AB  - Colorectal cancer is the second leading cause of cancer deaths in the United
      States. Despite proven screening strategies, less than 40% of eligible Americans
      undergo appropriate screening for colorectal cancer. Research evaluating the
      underlying defects responsible for hereditary nonpolyposis colorectal cancer and
      familial adenomatous polyposis has provided insight into some of the molecular
      mechanisms responsible for familial and sporadic colorectal cancer. The signaling
      pathways involved in the development of colorectal cancer may provide effective
      targets for prevention and treatment. These targets include cyclooxygenase-2,
      peroxisome proliferator activated receptor- delta, peroxisome proliferator
      activated receptor- gamma, transforming growth factor- beta receptors, and the
      inducible-nitric oxide synthase.

PMID- 17031154
TI  - The role of vitamin D in normal and pathologic processes in the colon.
AB  - Vitamin D(3) metabolites and analogues have recently been shown to play an
      important role in the regulation of a number of important cellular processes,
      including proliferation, differentiation, and apoptosis, in addition to their
      established roles in mineral homeostasis. The actions of these secosteroids
      involve both rapid, nongenomic effects and genomic effects; the latter mediated
      via the vitamin D receptor and other transcription factors. Their effects have
      been described in a variety of cell types, including normal and malignant
      colonocytes. This article summarizes the rapid and genomic actions of vitamin
      D(3) metabolites and analogues on normal and pathologic processes in the colon,
      with particular emphasis on the potential of these secosteroids to prevent colon
      cancer.

PMID- 17031155
TI  - Virtual colonoscopy: a new tool for colorectal cancer screening.
AB  - Virtual colonoscopy or computed-tomography colonography is a promising new method
      for colorectal cancer screening. Helical computed tomography is used to generate
      high-resolution, two-dimensional axial images of the abdomen and pelvis. Three
      dimensional images of the colon simulating those obtained with conventional
      colonoscopy can be reconstructed from the data obtained. Favorable attributes of
      virtual colonoscopy include its safety, high patient acceptance, and ability to
      provide a full structural evaluation of the entire colon. Multiple studies of
      virtual colonoscopy have been published in the literature in the past year
      regarding technique, image display, image reconstruction, clinical trial results,
      and feasibility as a screening tool. This manuscript will review the various
      studies in each of these areas.

PMID- 17031156
TI  - The role of radiation therapy in the adjuvant treatment of rectal cancer.
AB  - There have been several advances in the treatment of rectal cancer in the past 20
      years. The recognition that surgical therapy alone leads to a local failure rate
      of 15 to 50% in stages II and III has led to the use of adjuvant radiation
      therapy. Multiple prospective, randomized trials conducted by multi-institutional
      cooperative groups have resulted in the use of adjuvant combined modality therapy
      using radiation therapy and 5-fluorouracil chemotherapy. Some of the trials fine
      tuned the sequencing and dose of radiation and chemotherapy to maximize efficacy
      and minimize toxicity. The advent of accurate endorectal ultrasound and MRI
      staging has allowed the use of preoperative therapy without the unnecessary
      treatment of patients with early stage. This has resulted in greater sphincter
      preservation and fewer complications. The optimal sequencing of adjuvant therapy
      has yet to be found.

PMID- 17031157
TI  - Enteric nervous system, serotonin, and the irritable bowel syndrome.
AB  - Intestinal motility, secretion, and blood flow are controlled and integrated by
      the enteric nervous system (ENS). The ENS is like a "brain-in-the-gut," with many
      of the neurophysiologic properties of the central nervous system. Serotonin is a
      neurotransmitter at synapses in the microcircuits of the ENS. Serotonin is also
      released from enterochromaffin cells and inflammatory/immune cells to act at
      serotonergic receptors on neurons of the ENS. Four important actions are (1) fast
      and (2) slow excitation of enteric neurons, (3) presynaptic inhibition of
      neurotransmitter release at synapses in ENS microcircuits, and (4) excitation of
      intestinal sensory afferent fibers. Fast excitation and stimulation of sensory
      afferents are mediated by 5-HT(3) serotonergic receptors and slow excitation by 5
      HT(1P) receptors. Presynaptic inhibitory receptors are not conclusively defined.
      The efficacy of a new 5-HT(3) receptor blocking drug in the treatment of the
      diarrhea-predominant form of the irritable bowel syndrome in women suggests the
      importance of this receptor subtype in the mediation of neurogenic secretory
      diarrhea, motility abnormality, and abdominal pain and discomfort.

PMID- 17031158
TI  - Current world literature.

PMID- 17031160
TI  - Pathology of the liver.
AB  - Traditional anatomic pathology studies and molecular investigations both
      contributed to the breadth of current information in the field of liver pathology
      this year. Techniques such as reverse transcription polymerase chain reaction can
      identify recurrence of hepatitis C virus infection in the liver as early as 5
      days after transplantation. Chronic rejection after transplantation may be
      characterized not only by ductopenia but also by loss of portal tract hepatic
      artery branches. There are many diseases of small bile ducts in adults, and
      idiopathic adulthood ductopenia has been identified in extended family members.
      Adverse reactions to drugs may precipitate their removal from the pharmacopoeia,
      such as the many cases reported of severe bridging and submassive necrosis due to
      troglitazone (a thiazolidinedione antidiabetic agent). Several publications
      highlighted the association of hepatitis C virus infection with
      lymphoproliferative diseases and, newly, with cholangiocarcinoma.

PMID- 17031161
TI  - Cellular and molecular biology of the liver.
AB  - Recently, several lines of investigation focused on basic mechanisms governing
      cellular and molecular aspects of liver biology have intersected at the study of
      the hepatic stem cell. Despite years of study, the very question of the existence
      of the hepatic stem cell has yet to be unequivocally established. A second field
      of investigation into the cellular and molecular aspects of liver biology is
      aimed at liver-directed gene therapy in which several new vehicles have been
      devised to mediate gene transfer. Gene therapy is no longer thought of in the
      limited framework of a means to correct inherited disorders; it is now expanding
      into new therapeutic applications. A third major area of investigation includes
      studies of mechanisms that regulate membrane protein traffic necessary to
      maintain the integrity of differentiated liver cell function. In this review,
      some of the most recent advances and applications in these three areas are
      highlighted, and, where appropriate, points of interaction and potential
      therapeutic importance are emphasized.

PMID- 17031162
TI  - Alcoholic liver disease.
AB  - Research has substantiated the role of several mechanisms responsible for alcohol
      induced hepatotoxicity. These mechanisms include: oxidative stress and lipid
      peroxidation; immunogenic processes initiated by formation of protein adducts of
      acetaldehyde, other aldehydes and 1-hydroxyethyl radicals; and activation of
      Kupffer cells by endotoxin and subsequent cascade of events that involved
      cytokines, chemokines, and adhesion molecules. Increasing evidence implicates
      enhanced intestinal permeability caused by alcohol ingestion as the culprit that
      leads to endotoxemia. While oxidative stress is important, the principal source
      of reactive oxygen species that causes alcohol-induced liver injury is hotly
      debated. Potential sources may include cytochrome P450IIE1, activated Kupffer
      cells, and mitochondrial electron transfer chain. Apoptosis is likely an
      important pathway that culminates in hepatocyte cell death. Abstinence,
      corticosteroids, and enteral nutrition remain the cornerstones in the treatment
      of alcoholic hepatitis. The efficacies of medications such as S
      adenosylmethionine and pentoxifylline will need further confirmation by
      additional randomized trials before they can be recommended as standard therapies
      for alcoholic hepatitis.

PMID- 17031163
TI  - Metabolic liver disease.
AB  - The discovery of novel metabolic pathways and the genetic basis for diseases of
      the liver continues to yield new insights into the pathogenesis of inherited
      metabolic diseases of the liver, whereas the application of new technologies to
      their treatment continues to advance therapeutic options. This review of selected
      articles covers a wide range of subjects, from the identification of novel
      proteins and transport pathways to disease diagnosis and treatment of acute liver
      failure. Four selected topics, Wilson disease, hemochromatosis and iron overload
      disorders, alpha-1 antitrypsin disease, and exciting new therapeutic options for
      lysosomal storage diseases are the focus of this review.

PMID- 17031164
TI  - Drug-induced liver disease.
AB  - This year's review is divided into several sections: the first describes drug
      withdrawals and new general reviews of drug-induced liver disease (DILD),
      including a review of a classification of drug injury. We review agents newly
      described as causing DILD, and new reports of DILD from established agents
      appearing in the year 2000. New aspects regarding the treatment of acetaminophen
      toxicity are included, and in the final section we deal with prevention of DILD
      as well as issues surrounding the use of potentially hepatotoxic medications in
      patients with underlying chronic disease.

PMID- 17031165
TI  - Cholestatic syndromes.
AB  - New insights into the regulation of hepatobiliary transport proteins have
      provided the basis for a better understanding of the pathogenesis of cholestatic
      liver diseases. Mutations of transporter genes can cause hereditary cholestatic
      syndromes, the study of which has shed much light on the basic mechanisms of bile
      secretion and cholestasis. Important new studies have been published about the
      pathogenesis, clinical features, and treatment of primary biliary cirrhosis,
      primary sclerosing cholangitis, cholestasis of pregnancy, total parenteral
      nutrition-induced cholestasis, and drug-induced cholestasis.

PMID- 17031166
TI  - Hepatobiliary infections.
AB  - The major hepatobiliary infections (excluding the viral hepatitides) include
      amebic and pyogenic liver abscess and cholangitis. Little new information has
      been published in the area of cholangitis during the last several years. In
      contrast, the clinical presentation and management of liver abscess have evolved
      considerably, not only in the last several years but also during a more extended
      period spanning the last two decades. In the United States, amebic liver abscess
      occurs largely in individuals from endemic areas or in those traveling to endemic
      areas. Recent data suggest that patients with human immunodeficiency virus (HIV)
      infection are at an increased incidence of amebic liver abscess. New serologic
      tests and molecular techniques are being added to the diagnostic armamentarium
      for amebic liver abscess. In most cases, amebic liver abscess is associated with
      an excellent prognosis (up to 100% survival) if properly managed. Pyogenic liver
      abscess, although commonly occurring in patients with known biliary tract
      disease, is often cryptogenic in origin (ie, no clear causal factor can be
      identified) or often is caused by underlying medical disorders. An emerging
      population of patients with pyogenic liver abscess includes those with
      complications of aggressive interventions (hepatic chemoembolization,
      cryoablation, liver transplantation). Pyogenic liver abscess was predominantly
      managed by surgical methods up until the early 1980s, but almost entirely has
      changed to being managed by interventional techniques; in 2000, this trend has
      continued. In contrast to amebic liver abscess, pyogenic liver abscess is
      associated with greater morbidity and mortality, ostensibly caused by the
      severity of the underlying disease in many patients. However, it should be
      emphasized that the prognosis of patients with pyogenic liver abscess, who do not
      have underlying comorbid conditions, is excellent.

PMID- 17031167
TI  - Viral hepatitis.
AB  - Viral hepatitis constitutes the most common entity seen in hepatology practice.
      Hepatitis A vaccination is recommended for patients with chronic hepatitis. Both
      lamivudine and interferon are established therapies against chronic hepatitis B,
      with other treatments not equally effective. Adefovir dipivoxil is a promising
      new treatment for lamivudine-resistant hepatitis B mutants. Lamivudine and
      hepatitis B immunoglobulin are effective in preventing recurrence of hepatitis B
      after transplantation. The combination of interferon and ribavirin has been shown
      to be effective for treatment of hepatitis C. Studies support the antiviral,
      antifibrotic, and antineoplastic effect of interferon therapy. Recurrence of
      hepatitis C after transplantation has been associated with more rapid progression
      to cirrhosis. Other major advances in the field of viral hepatitis during the
      past year are highlighted.

PMID- 17031168
TI  - Autoimmune liver disease.
AB  - Autoimmune hepatitis in children may be associated with sclerosing cholangitis in
      the absence of inflammatory bowel disease. Wilson disease can have clinical and
      laboratory features that resemble autoimmune hepatitis, and it may respond
      initially to corticosteroids. Soluble HLA-DR antigens reflect clinical activity,
      and they may be useful markers of treatment response. Polymorphisms of the
      cytotoxic T lymphocyte antigen-4 gene may synergize with other autoimmune
      promoters or HLA risk factors to increase susceptibility and alter disease
      expression. DRB1*1301 distinguishes Argentine children from Argentine adults and
      identifies a unique subgroup. Antibodies to soluble liver antigen/liver-pancreas
      do not characterize a separate clinical entity. Their target antigen has been
      isolated, and it shares homologies with a selenocysteine-specific protecting
      factor (tRNP((Ser)Sec)). CYP2D6 is expressed on the hepatocyte surface, and it
      can be targeted by antibodies in autoimmune hepatitis and chronic hepatitis C.
      Perinuclear antineutrophil cytoplasmic antibodies lack sensitivity and
      specificity for autoimmune hepatitis, and they have diverse antigen
      specificities. Activation-induced cell death may be impaired in autoimmune
      hepatitis, and, in contrast to budesonide, mycophenolate mofetil has been
      effective in a small study of problematic patients.

PMID- 17031169
TI  - Hepatocellular carcinoma.
AB  - The number of papers published regarding hepatocellular carcinoma between 1999
      and 2001 increased from previous years. This year a study confirmed the increase
      in incidence in the United States. Also, several studies established for the
      first time that tobacco smoking was a risk factor for the development of this
      tumor. Several studies established that the process of angiogenesis is critical
      for the development of hepatocellular carcinoma, and one paper indicated that
      inhibiting this process might lead to possible treatment of this tumor. Resection
      was compared with liver transplantation for the first time in two studies. It was
      shown that transplantation offered the overall best long-term option, but in a
      certain group of patients without portal hypertension and well-preserved liver
      function resection is the best option.

PMID- 17031170
TI  - Portal hypertension.
AB  - Portal hypertension is the main complication of cirrhosis and is responsible for
      its most common complications: variceal hemorrhage, ascites, and portosystemic
      encephalopathy. Portal hypertension is the result of increased intrahepatic
      resistance and increased portal venous inflow, which in turn is the result of
      splanchnic vasodilatation. Vasodilatation (splanchnic and systemic) and
      hyperdynamic circulation are hemodynamic abnormalities typical of cirrhosis and
      portal hypertension. Gastroesophageal varices result almost solely from portal
      hypertension, although the hyperdynamic circulation contributes to variceal
      growth and hemorrhage. Ascites results from sinusoidal hypertension and sodium
      retention, which is, in turn, secondary to vasodilatation and activation of
      neurohumoral systems. The hepatorenal syndrome represents the result of extreme
      vasodilatation with an extreme decrease in effective blood volume that leads to
      maximal activation of vasoconstrictive systems, renal vasoconstriction, and renal
      failure. Spontaneous bacterial peritonitis is a potentially lethal infection of
      ascites that occurs in the absence of a local source of infection. Portosystemic
      encephalopathy is a consequence of both portal hypertension (shunting of blood
      through portosystemic collaterals) and hepatic insufficiency that result in the
      accumulation of neurotoxins in the brain. This paper reviews the recent advances
      in the pathophysiology and management of the complications of portal
      hypertension.

PMID- 17031171
TI  - Acute liver failure.
AB  - Worldwide, viral hepatitis is the leading cause of acute liver failure, whereas
      acetaminophen hepatotoxicity is the most commonly identified cause in Western
      countries. Restricting the quantity of acetaminophen tablets dispensed has been
      shown to reduce morbidity and mortality in countries with a high incidence of
      acetaminophen overdose. Troglitazone and bromfenac are two recently approved
      medications that were withdrawn from the market due to an unacceptably high
      incidence of severe hepatotoxicity. In addition, trovafloxacin, nefazodone, and
      ritonavir were reported to be associated with severe hepatitis and acute liver
      failure. Moderate hypothermia is a simple and potentially effective means of
      reducing intracranial pressure in patients with acute liver failure and cerebral
      edema. However, controlled clinical trials are needed to determine proper patient
      selection and optimize treatment. Extracorporeal bioartificial liver support
      devices remain an exciting but as yet unproven means of supporting acute liver
      failure patients with advanced encephalopathy. Living donor liver transplantation
      has recently been reported for adults and children with acute liver failure.
      However, ethical concerns regarding donor safety and the ability to obtain
      informed consent without coercion have been raised. Lastly, advances in the
      identification and isolation of pluripotent liver stem cells in human bone marrow
      provides hope for a simple and effective means of enhancing native liver
      regeneration.

PMID- 17031172
TI  - Liver transplantation.
AB  - Continued discussion over organ allocation and distribution remained a focal
      point in the field of liver transplantation in the year 2000. Despite the ongoing
      debate, no significant changes were implemented in the current allocation system.
      By far, the most widely discussed topic in liver transplantation this year was
      live donor adult-to-adult liver transplantation. Several authors reported on
      their initial experience, with both recipient and donor outcomes appearing
      excellent. As the number of transplant centers performing this procedure
      increases we look forward to further studies regarding the safety and long-term
      outcome of this innovative procedure. Studies on viral hepatitis after liver
      transplantation again focused on the problem of recurrent hepatitis B and
      hepatitis C. Several small studies found benefit in patients with hepatitis B
      treated with intramuscular hepatitis B immunoglobulin and lamivudine after
      transplantation. Although breakthrough replication remains a problem in some
      patients, these studies offer hope that combination therapy for hepatitis B may
      provide improved long-term graft survival in these patients. In patients with
      hepatitis C, several studies focused on identifying risk factors to predict graft
      recurrence of the virus after liver transplantation. Both cellular rejection and
      level of viral replication may be important predictors of recurrent hepatitis C
      virus in the graft. Early treatment reports using interferon and ribavirin
      suggest that some patients may have a viral response during therapy; however, it
      is short lived, and tolerance of medication is difficult. Certainly, we look
      forward to further studies looking at means of prevention and treatment of viral
      hepatitis in patients undergoing liver transplantation.

PMID- 17031173
TI  - Bibliography. Current world literature. Inflammatory bowel disease.

PMID- 17031175
TI  - Mechanisms of tissue damage in inflammatory bowel disease.
AB  - Crohn disease and ulcerative colitis are caused by an excessive immune
      inflammatory reaction in the intestinal wall. Analysis of the types of immune
      response ongoing in the inflamed intestine has revealed that in Crohn disease
      there is predominantly a T helper cell type 1 response, with exaggerated
      production of interleukin (IL)-12 and interferon-gamma, whereas in ulcerative
      colitis the lesion seems to be more of an antibody-mediated hypersensitivity
      reaction. Despite these differences, downstream inflammatory events are probably
      similar in both conditions. In both Crohn disease and ulcerative colitis there is
      an increased synthesis of proinflammatory cytokines, including IL-1beta, IL-6, IL
      8, IL-16, and tumor necrosis factor-alpha accompanying the influx of nonspecific
      inflammatory cells into the mucosa. These cytokines contribute to the tissue
      damage either directly or indirectly by enhancing the production of matrix
      metalloproteinases and growth factors, which produce ulceration as well as
      mucosal repair.

PMID- 17031176
TI  - Mechanisms of tissue protection and repair in inflammatory bowel disease.
AB  - Investigators have increasingly appreciated the importance of the breakdown of
      the epithelial barrier in the pathogenesis of inflammatory bowel disease.
      Epithelial cells secrete trefoil factors, heat shock proteins, and secretory
      leukocyte proteinase inhibitors that protect the integrity of the epithelial
      barrier. Other agents, including growth factors, regulate the repair of the
      epithelium after injury has occurred. Drugs that would either enhance protection
      of barrier function from injury or accelerate repair after injury would have
      therapeutic potential in inflammatory bowel disease.

PMID- 17031177
TI  - Intestinal fibrosis in human and experimental inflammatory bowel disease.
AB  - Fibrosis is a serious complication of Crohn disease for which there is no
      effective therapy. It is unclear why fibrosis, particularly fibrosis of the
      mucosal layer, develops in Crohn disease and not in ulcerative colitis. Smooth
      muscle cells, subepithelial myofibroblasts, and fibroblasts have traditionally
      been considered mediators of fibrosis, but new information points to a role of
      interstitial cells of Cajal and mast cells. Recent evidence about the role of
      each of these cell types in fibrosis in Crohn disease or other inflammatory bowel
      diseases is described. Hypothetical models to describe how altered function of
      these cells could underlie fibrosis of the mucosa or submucosal layers are
      presented. Fibrosis is not well characterized in any animal model of inflammatory
      bowel disease. The merits of several animal models for defining the mechanisms of
      inflammation-induced intestinal fibrosis are reviewed.

PMID- 17031178
TI  - Intestinal microflora in human and experimental inflammatory bowel disease.
AB  - Commensal luminal bacteria stimulate protective or tolerogenic mucosal immune
      responses in normal (ie, resistant) hosts and detrimental responses, which result
      in chronic intestinal inflammation, in genetically susceptible hosts. Enteric
      pathogens appear to be important in the initiation and reactivation of human
      inflammatory bowel disease, and may be responsible for chronic inflammation in at
      least a subset of patients with inflammatory bowel diseases. Individual
      components of the commensal flora have variable abilities to induce inflammatory
      and protective immune responses; these preferential immune responses to
      individual bacterial species may be unique to each host's genetic background.
      Analogous to the balance between pro- and antiinflammatory cytokines and T-cell
      subsets, the ratio between protective (ie, probiotic) and aggressive commensal
      bacteria may determine whether there is mucosal homeostasis or chronic, relapsing
      intestinal inflammation. Therapeutic alteration of the luminal microenvironment
      by probiotic, prebiotic, and molecular strategies offers great promise for
      nontoxic treatment of inflammatory bowel disease.

PMID- 17031179
TI  - Probiotics and antibiotics in inflammatory bowel disease.
AB  - Many experimental and clinical observations suggest a potential role for
      intestinal microflora in the pathogenesis of inflammatory bowel disease.
      Manipulation of the luminal content using antibiotics and/or probiotics may
      represent a potentially effective therapeutic option. Results of antibiotic
      treatment in inflammatory bowel disease are controversial, but this approach is
      frequently and successfully adopted in clinical practice. Recent data support the
      potential therapeutic role of probiotics in inflammatory bowel disease. In
      particular, a highly concentrated probiotic preparation was shown to be superior
      to placebo both on the prevention of pouchitis onset and of chronic pouchitis
      relapse. Its role in the maintenance treatment of ulcerative colitis and Crohn
      disease needs to be further assessed by large, double-blind, controlled trials.
      Future research needs to be focused on obtaining more precise information on the
      enteric microflora and the mechanisms of action of probiotics.

PMID- 17031180
TI  - Medical management of inflammatory bowel disease: old and new perspectives.
AB  - The treatment of inflammatory bowel disease is a continually evolving area and a
      major focus of the current literature in gastroenterology. As further information
      is gained in the areas of etiology, pathophysiology, and natural history of the
      disease, new agents are developed, and management strategies are revised. The
      contribution of this year's clinically based literature is reviewed in this
      summary and incorporated into specific management strategies.

PMID- 17031181
TI  - Nutrition in inflammatory bowel disease: impact on disease and therapy.
AB  - Nutritional derangements are frequent in inflammatory bowel disease. In the last
      year, significant work was published examining the mechanisms of impaired food
      intake in animal models of inflammatory bowel disease, which allow a better
      understanding of these processes. These data have shed new light on the relative
      role of underfeeding and inflammation on the growth retardation associated with
      intestinal inflammation. Other studies have provided further information on the
      risk factors and predictive biomarkers of bone loss in patients with inflammatory
      bowel disease. The potential role of enteral nutrition as primary therapy for
      Crohn disease is particularly addressed in the present review. Recent
      contributions emphasized the special importance of this therapeutic modality in
      pediatric patients, but the possible mechanisms for such therapeutic effect are
      still not well understood. Other nutrients may have a therapeutic potential in
      inflammatory bowel disease. In particular, recent data on the in vivo
      antiinflammatory action of butyrate merit special mention. Finally, novel
      nutritional therapeutic strategies for inflammatory bowel disease, such as
      transforming growth factor-beta2-enriched enteral feeding or hydrothermally
      processed cereals, have recently been explored.

PMID- 17031182
TI  - Pediatric inflammatory bowel disease: clinical and therapeutic aspects.
AB  - Epidemiologic data suggest that the incidences of pediatric ulcerative colitis
      and Crohn disease continue to evolve with geographic variations. One study
      suggests that children with autism have a unique inflammatory bowel disorder that
      is associated with gastrointestinal symptoms. The appropriate use of new
      diagnostic tests and novel treatments for inflammatory bowel disease (IBD) needs
      to be clarified in the pediatric population. Because of concerns regarding
      sensitivity and specificity, serologic markers measuring anti-Saccharomyces
      cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies
      cannot yet replace conventional diagnostic testing for screening or diagnosis of
      pediatric IBD. Large, prospective, pediatric population-based studies still need
      to be performed to ascertain their use as a noninvasive screening tool. Genetic
      studies using thiopurine methyl transferase and measurement of 6-mercaptopurine
      metabolites appear to be valuable for management of pediatric patients with IBD,
      in assisting clinicians in optimizing therapeutic response to 6-mercaptopurine,
      and in identifying individuals at increased risk for drug-induced toxicity. Newer
      immunomodulatory agents also are being explored in pediatric IBD. Open pilot
      trials of infliximab (Remicade; Centocor, Malvern, PA) for the treatment of
      children with Crohn disease that does not respond to conventional management have
      demonstrated short-term efficacy and safety. Trials of tacrolimus for treatment
      of fulminant colitis in children have been disappointing.

PMID- 17031184
TI  - Gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a chronic disorder that affects
      millions of people worldwide and has the potential to lead to serious
      consequences, including cancer of the esophagus. It for this reason that there is
      such intense interest in the topic, this emphasized by the identification of some
      341 articles published in the English language in the year 2000 alone. The
      present report highlights the results of a number of studies that either increase
      our understanding of the condition or raise important issues about its diagnosis
      and treatment. Included in the areas covered are (1) the role of genetics in
      GERD; (2) the mechanism for transient lower esophageal sphincter relaxations and
      their association with hiatal hernias; (3) the role of Helicobacter pylori in
      GERD and Barrett esophagus; (4) efficacy and safety of proton pump inhibitors in
      GERD; and (5) the mechanism for chronic cough in patients with GERD, among
      others.

PMID- 17031186
TI  - Chest pain of esophageal origin.
AB  - Chest pain of esophageal origin or noncardiac chest pain is reported by at least
      a fifth of the general population. Recent literature focused on further
      understanding mechanisms of chest pain in subset of patients with functional
      chest pain of presumed esophageal origin. Studies have demonstrated concurrent
      visceral and somatic pain hypersensitivity, and amplified secondary allodynia, in
      patients with noncardiac chest pain (NCCP), suggesting central sensitization.
      Other studies have demonstrated abnormal cerebral processing of intraesophageal
      stimuli. However, gastroesophageal reflux disease (GERD) has remained the most
      common esophageal cause of NCCP. The introduction of the proton pump inhibitor
      test, a highly sensitive and cost-effective diagnostic strategy, simplified our
      diagnostic approach toward patients with GERD-related NCCP. For patients with
      positive proton-pump-inhibitor test results, long-term treatment with antireflux
      medication is warranted. For patients with non-GERD-related NCCP, pain modulators
      remain the cornerstone of therapy.

PMID- 17031185
TI  - Esophageal motor disorders.
AB  - Esophageal motor function remains of investigative and clinical interest because
      of its relevance to symptoms and its relation to the occurrence and management of
      gastroesophageal reflux disease. Refinement in diagnostic methods continues to
      occur, and improved tests for identifying the nature or severity of motor
      disturbances in both the proximal and distal esophageal regions are now well
      described. Controversy concerning the management of achalasia, the best
      understood distal motor disorder, is resolving as the benefits and disadvantages
      of available treatment options are becoming recognized. The relation of
      esophageal motor dysfunction to outcomes from antireflux surgery remains
      incompletely understood.

PMID- 17031187
TI  - Barrett esophagus.
AB  - There continues to be great interest in Barrett esophagus, the premalignant
      lesion for adenocarcinoma of the esophagus and the esophagogastric junction.
      There were several publications this past year related to the epidemiology,
      pathogenesis, new methods for detection, biomarkers for stratifying patients by
      risk, and the treatment of patients with Barrett esophagus. Patients with
      intestinal metaplasia in short lengths of columnar mucosa in the distal esophagus
      (ie, short-segment Barrett esophagus) appear to be distinct from those with
      intestinal metaplasia in the gastric cardia. The reported risk of cancer in
      patients with Barrett esophagus is probably subject to publication bias, with
      small series reporting a higher incidence of cancer. New methods for the
      diagnosis and detection of intestinal metaplasia and dysplasia are being
      evaluated and may, in future, help in obtaining more accurate screening and more
      focused surveillance of patients with Barrett esophagus. The validation of
      biomarkers may help us to risk stratify patients at high risk for cancer
      development. Endoscopic mucosal resection appears to be a safe and effective
      technique for the resection and accurate diagnosis of dysplastic or cancerous
      areas within Barrett esophagus.

PMID- 17031188
TI  - Endoscopic therapeutic esophageal interventions.
AB  - Despite numerous advances in the chemotherapeutic, radiotherapeutic, and surgical
      treatment of esophageal cancer, most patients require some type of endoscopic
      palliation for dysphagia during the course of their illness. Numerous modalities
      exist, including thermal ablation with neodymium:yttrium-aluminum-garnet laser,
      argon plasma coagulation, electrocautery, nonthermal ablation with alcohol
      injection or photodynamic therapy, or displacement of tumor with endoscopically
      placed stents. Each therapy carries with it a unique profile of efficacy and
      complications. Some therapies may be more appropriate for certain tumor locations
      and morphologies than others. During the past year, new studies have defined
      these parameters further. However, it remains essential that the endoscopist have
      both a thorough knowledge of these various modalities and an ability to chose
      among them when undertaking endoscopic palliation of this difficult and rapidly
      rising disease.

PMID- 17031189
TI  - Esophageal cancer.
AB  - Accurate pretherapy staging for esophageal cancer is important for stage-directed
      therapy. Precise staging is also essential for quality control and ensuring the
      validity of clinical trials. Endoscopic ultrasound is currently the best
      technique in local regional staging. Various investigators have attempted to
      overcome the problems of nontraversable lesions and restaging after neoadjuvant
      therapy. Positron emission tomography scan was shown to be especially useful in
      identifying distant metastases. Its more widespread use is likely to impact on
      treatment strategies. Surgical resection remains the mainstay of treatment of
      esophageal cancer. Improvement in immediate postoperative morbidity, mortality,
      and long-term survival was shown by various reports to relate to experience and
      volume. The concept of three-field dissection was further defined by illustrating
      the importance of lymphadenectomy around the recurrent laryngeal nerves.
      Multimodality treatments continue to receive attention. Several studies have
      established the patterns of practice in the United States in treating esophageal
      cancer. Chemoradiation programs are gaining a more important role and are widely
      used, although their exact roles are uncertain. Closely related to this area of
      research is the search of molecular markers of favorable response to such
      therapies. Concerning palliative treatment for esophageal cancer, self-expanding
      metallic stents have a definite role in patients with malignant dysphagia. Their
      results and complications are reviewed. Lastly, quality-of-life issues have
      assumed more importance in studies in oncology. Prospective quality-of-life data
      should be evaluated in future studies on different treatment methods for this
      deadly disease.

PMID- 17031190
TI  - Surgery, radiotherapy, and chemotherapy for esophageal carcinoma.
AB  - Over the last year, several interesting studies have been published on the
      treatment of esophageal carcinoma. Surprisingly, none of them was a randomized
      phase III trial. The debate on the necessary extent of a potentially curative
      surgical resection is ongoing. After initially disappointing results, the
      innovative technique of minimally invasive surgery draws new attention, but clear
      advantages for the endoscopic approach are yet to emerge. An updated meta
      analysis on the value of preoperative radiotherapy showed negative results. There
      is a clear tendency toward combined-modality treatment, especially in patients
      with more advanced disease. Some new chemotherapeutic agents showed promising
      preliminary results (especially paclitaxel), whereas others were clearly
      disappointing (eg, gemcitabine, topotecan). Concurrent chemoradiation as primary
      treatment for proximal (cervical) tumors was remarkably effective.

PMID- 17031191
TI  - Bibliography. Current world literature. Pancreas.

PMID- 17031193
TI  - Receptor biology and signal transduction.
AB  - This year has witnessed substantial advances in receptor biology and signal
      transduction that are relevant to the function and regulation of the healthy
      pancreas and to the pathogenesis and potential therapy of pancreatitis and
      pancreatic carcinoma. There has been an expansion in the cast of pancreatic
      regulatory molecules, now including protease-activated receptors, chemokines, and
      chemokine receptors. There have been new insights into the cellular distribution
      and signaling initiated at the classic pancreatic receptors. There have also been
      dramatic advances in insights into the structure of G protein-coupled receptors,
      with the first solution of a crystal structure of a member of this superfamily,
      and into the molecular basis of ligand binding and activation of these important
      molecules. This will clearly improve the opportunities for the rational design
      and refinement of receptor-active drugs. In addition to these fundamental
      advances, there has been renewed attention to the expression, function, and
      regulation of receptors and signaling pathways in pancreatic cells present in the
      setting of pancreatitis and pancreatic carcinoma. It is hoped that this will
      contribute toward earlier diagnosis, more successful therapy, and new
      chemopreventive strategies for these illnesses.

PMID- 17031194
TI  - Neurohormonal control of exocrine pancreas.
AB  - The exocrine pancreas is regulated by various hormonal factors derived from the
      gut through hormone-hormonal and neurohormonal interactions. Physiologic stimuli
      entering the upper small intestine elicit the release of intestinal hormones and
      activate sensory reflex mechanisms from the intestinal mucosa to stimulate or
      inhibit exocrine pancreatic secretion. In addition, the endocrine pancreas,
      intrapancreatic nerves, and some extrapancreatic neural pathways, with or without
      mediation by the vagus nerve, are known to participate in regulation of exocrine
      pancreatic secretion. It has been established that two key intestinal hormones,
      secretin and cholecystokinin (CCK), in physiologic doses, act through the vagal
      afferent pathway and interact with each other as well as with other gut hormones.
      The releases of these two hormones are mediated through the corresponding
      releasing peptides. In the past few years, the roles of secretin- and CCK
      releasing peptides have become more clearly defined. The participation of several
      neurotransmitters and regulatory peptides in the regulation of exocrine
      pancreatic secretion has also been established. In addition, neurotransmitters
      and neuropeptides released from the central nervous system may participate in the
      regulation of pancreatic secretion. It is conceivable that a few
      neurotransmitters and neuropeptides are involved in each neural regulatory
      pathway. However, their roles and sites of action in each pathway remain to be
      determined.

PMID- 17031195
TI  - Acute pancreatitis.
AB  - The pathophysiologic concept of acute pancreatitis focuses on early events inside
      acinar cells such as activation of trypsin. Despite significant progress in the
      understanding of molecular events in experimental pancreatitis, knowledge of
      these mechanisms has not yet been translated into therapeutic strategies useful
      in humans. A single morphologic or laboratory marker reliably predicting the
      individual course of acute pancreatitis still awaits discovery. The clinical
      outcome of acute pancreatitis is dependent on the presence of necrosis and
      systemic complications. The extent of the systemic inflammatory response to local
      pancreatitis seems to be the rate-limiting step. Several mechanisms shed light on
      the interconnectivity between intra-acinar protease activation and
      immunoregulatory processes. Deciphering these cell biologic connections has
      already had an impact on the clinical management of patients and the
      identification of prognostic markers in human disease. However, further
      investigations of pancreatic pathophysiology are needed to initiate novel
      therapeutic strategies.

PMID- 17031196
TI  - Chronic pancreatitis.
AB  - An increasing number of novel mutations are associated with chronic pancreatitis.
      Some cause a high-penetrance, autosomal dominant type of clinical picture (eg,
      mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others
      have a low penetrance or are frequent in the general population (eg, mutations in
      Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen
      gene) and act as disease modifiers. The results of recent studies indicate that
      smoking adversely affects the course and complications of chronic pancreatitis
      (more frequent and faster rate of calcification and higher risk of development of
      pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients
      with this condition should not smoke. Using current diagnostic criteria, the
      accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is
      not good. For example, 39% of dyspeptic persons without any other evidence of
      chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic
      pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not
      prevented or increased by pancreatic surgery. Islet cell autotransplantation
      holds promise for the prevention of diabetes in patients requiring total
      pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein
      occlusion is present in 7% of patients undergoing surgery for chronic
      pancreatitis, but fewer than one fifth of these patients have variceal bleeding
      before or after surgery.

PMID- 17031197
TI  - TGFbeta-mediated signaling and transcriptional regulation in pancreatic
      development and cancer.
AB  - Transforming growth factor-beta (TGFbeta) plays a critical role in pancreatic
      development and cell proliferation. Binding of TGFbeta to its membrane receptor
      kinases activates the Smad signaling proteins, allowing them to translocate to
      the nucleus and participate in the transcriptional control of TGFbeta target
      genes. In addition, there is an increasing number of cellular mechanisms
      affecting the final response of a cell to TGFbeta. This includes crosstalk with
      other signaling pathways and the induction of TGFbeta early response genes, such
      as the TGFbeta-inducible early response gene (TIEG) family of transcription
      factors. Like the Smads, TIEGs behave as downstream effector proteins in TGFbeta
      mediated pancreatic growth control. The discovery of the Smads and TIEGs has
      provided new insights into TGFbeta-regulated functions. Their significance in
      pancreatic development and cancer is discussed in this review.

PMID- 17031198
TI  - Pancreatic surgery.
AB  - Recent advances have been made in both laparoscopic and endoscopic techniques for
      diagnosing and treating pancreatic neoplasms. These advances are reviewed. In
      addition to the traditional methods of pancreatic resection (eg, standard Whipple
      and pylorus-preserving Whipple), several other techniques have been described and
      are discussed (eg, median pancreatectomy and extended pancreatectomy). The
      morbidity and mortality rates of pancreatic operations have diminished, but
      significant complications still occur (eg, delayed gastric emptying, pancreatic
      fistula, and biliary strictures). These are discussed. In managing acute and
      chronic pancreatitis, less invasive and more conservative approaches are being
      advocated.

PMID- 17031199
TI  - Biliary tract.

PMID- 17031200
TI  - Biliary tract cancer.
AB  - Advances in cellular and molecular biology of extrahepatic cholangiocarcinoma and
      gallbladder adenocarcinoma are providing innovative means for the diagnosis and
      treatment of biliary tract cancer. Similarly, refinements in noninvasive studies-
      including helical computed tomography, magnetic resonance
      cholangiopancreatography, and endoscopic ultrasonography--are enabling more
      accurate diagnosis, staging, and treatment planning for these tumors. Complete
      resection remains the only means for cure, and recent reports from major
      hepatobiliary centers support aggressive wide resection for bile duct and
      gallbladder cancer. Palliation of malignant strictures has improved with advanced
      endoscopic techniques, newer polyurethane-covered stents, endoscopic microwave
      coagulation therapy, and radiofrequency intraluminal endohyperthermia. The
      preliminary data on such minimally invasive techniques suggest an improvement in
      quality of life and survival for selected patients.

PMID- 17031201
TI  - Sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic disease that may have an
      autoimmune basis. Most patients have a circulating antineutrophil cytoplasmic
      antibody that appears to be targeted against a 50-kD nuclear envelope protein.
      The clinical applications of this antibody have not yet been defined. Other
      autoantibodies directed against antigens, such as cathepsin G, elastase, and
      anticardiolipin, may also be detected in some patients. It is suggested that
      primary sclerosing cholangitis may have a bacterial cause. Helicobacter gene
      sequences have been detected in liver tissues in primary sclerosing cholangitis.
      The role of Helicobacter spp and other bacteria in the etiopathogenesis of
      primary sclerosing cholangitis remains to be determined. Primary sclerosing
      cholangitis may overlap with autoimmune hepatitis in some cases, although the
      real prevalence of this association remains to be determined. Many prognostic
      models have been created, but they lack cross-validation, and their clinical
      usefulness remains limited. Endoscopic retrograde cholangiography remains the
      gold standard for diagnosis, but magnetic resonance imaging may be a viable
      alternative in many cases. Clinical trials with cladibrine, pentoxifylline, and
      budesonide have failed to demonstrate benefits. Orthotopic liver transplantation
      remains the only effective treatment.

PMID- 17031202
TI  - Gallstones.
AB  - Gallstones are estimated to affect over 20 million people in the United States.
      Recent studies have clarified the role of various dietary components in gallstone
      disease. Also, insulin resistance has been demonstrated to be a risk factor for
      gallstones. Other research has focused on the pathophysiology of gallstones and
      on clarifying the underlying mechanisms of previously noted risk factors for
      gallstones. New techniques for the noninvasive diagnosis of bile duct stones
      continue to be developed and tested. These techniques include computed tomography
      and magnetic resonance cholangiography. The impact and appropriateness of
      laparoscopic cholecystectomy continue to debated, and studies point to both
      overuse and underuse of this operation in the management of the disease.

PMID- 17031203
TI  - Endoscopic management of biliary tract disease.
AB  - New investigations, evaluation of controversial issues, and advances in
      technology continue to shape the endoscopic management of biliary disorders. This
      article discusses recent literature related to the diagnosis and therapy of
      biliary tract disease. Specifically, the diagnosis and management of
      choledocholithiasis, complications of biliary endoscopy and potential preventive
      measures, roles for endosonography in the evaluation of biliary disease, and
      endoscopic therapy of postoperative liver transplantation complications are
      reviewed. Recent advances in biliary stents and the use of cholangioscopy in
      biliary disorders are also assessed.

PMID- 17031204
TI  - Liver involvement in childhood histiocytic syndromes.
AB  - The histiocytic syndromes of childhood are disorders of the reticuloendothelial
      system with variable clinical manifestations. Included among them are Langerhans
      cell histiocytosis and hemophagocytic lymphohistiocytosis. This discussion will
      be restricted to these two disorders. Liver disease in these conditions is
      common. Langerhans cell histiocytosis is characterized by the abnormal clonal
      proliferation of the macrophage-derived Langerhans cell. Liver involvement at
      diagnosis has management and prognostic significance. In a subgroup of patients,
      sclerosing cholangitis develops, which may lead to end-stage liver disease
      requiring liver transplantation. Hemophagocytic lymphohistiocytosis is a disease
      of abnormally activated macrophages that can involve multiple organ systems,
      including the liver. Differentiation between this disorder and other causes of
      pediatric liver disease is critical, because treatment strategies include
      chemotherapy, immunosuppression, and frequently bone marrow transplantation.

PMID- 17031205
TI  - Bibliography. Current world literature. Stomach and duodenum.

PMID- 17031207
TI  - Gastric secretion.
AB  - The influence of central and peripheral stimuli on gastric acid secretion is
      mediated via activation of histaminergic, gastrinergic, and cholinergic pathways
      coupled to intracellular second-messenger systems that determine the trafficking
      and activity of H+ K+-ATPase, the proton pump of the parietal cell. Histamine,
      released from enterochromaffin-like cells stimulates the parietal cell directly
      via H-2 receptors coupled to generation of cAMP. Gastrin, acting via
      cholecystokinin-2 receptors on enterochromaffin-like cells coupled to an increase
      in intracellular calcium, stimulates the parietal cell indirectly by activating
      histidine decarboxylase, releasing histamine, and inducing enterochromaffin-like
      cell hypertrophy and hyperplasia. Acetylcholine, released from gastric
      postganglionic intramural neurons, stimulates the parietal cell directly via M-3
      receptors coupled to intracellular calcium release and calcium entry. The second
      messenger systems activated in the parietal cell converge on H+ K+-ATPase that
      catalyzes the exchange of luminal K+ for cytoplasmic H+ and is responsible for
      gastric luminal acidification. The main inhibitor of acid secretion is
      somatostatin which, acting via sst2 receptors, exerts a tonic inhibitory
      influence on parietal, enterochromaffin-like, and gastrin cells. Acute infection
      with Helicobacter pylori results in hypochlorhydria, whereas chronic infection
      may be associated with either hypo- or hyperchlorhydria. Although prostaglandins
      are thought to play a physiologic role in the regulation of acid secretion and
      maintenance of gastric mucosal integrity, the precise roles of cyclooxygenase-1
      and cyclooxygenase-2 in these processes still eludes us.

PMID- 17031208
TI  - Gastroduodenal mucosal defense: coordination by a network of messengers and
      mediators.
AB  - Gastroduodenal mucosal defense is composed of structural features of the mucosa,
      cellular monitors of pending or actual injury, and a web of effector cells that
      protect the mucosa from damage and govern its recovery from injury. By virtue of
      these systems, the gastroduodenal mucosa can cope with the harmful ingredients of
      ingested food and the potentially deleterious effects of gastric acid and pepsin.
      It is increasingly appreciated that a network of chemical messengers coordinates
      the alarm, defensive, and healing mechanisms. This article highlights some of the
      advances from the past year that have furthered our understanding of the
      regulatory systems that govern gastroduodenal mucosal homeostasis. Particular
      emphasis is given to control of the mucous and epithelial phospholipid barriers,
      the mucosal microcirculation, and the epithelial, neural, immune, and
      inflammatory mediators of the mucosal repair mechanisms.

PMID- 17031209
TI  - The medical treatment of peptic ulcer disease.
AB  - There is continued interest in the role of H. pylori in both uninvestigated and
      non ulcer dyspepsia. The literature on this issue provided interesting, if at
      times conflicting findings, leaving the clinician with little choice but to use
      clinical judgment when dealing with these patients. On the Therapeutic front, a
      "new" proton pump inhibitor, with impressive early efficacy data has been
      launched, while an i.v. proton pump inhibitor formulation has reached a number of
      markets. Emerging data on the use of potent acid suppression in especially GI
      bleeding will almost certainly impact on the use of these agents. The
      gastrointestinal effects of low dose aspirin use have received attention, while
      the COX1-sparing agents have now started to impact on clinical practice. Two
      large clinical outcomes studies with these agents have been published. Both
      indicate at least some benefit, but raise interesting questions with regard to
      the use of these agents in the clinical setting.

PMID- 17031210
TI  - Nonsteroidal anti-inflammatory drug gastrointestinal toxicity.
AB  - Toxic effects in the upper gastrointestinal tract, primarily complicated gastric
      and intestinal ulcers, are the most common undesirable effects of the
      nonsteroidal anti-inflammatory drugs. During the last several years, there have
      been several advances, both in the laboratory and clinically, toward reducing
      nonsteroidal anti-inflammatory drugs' gastrointestinal toxicity. Some of these
      important developments are the delineation of mechanisms of nonsteroidal anti
      inflammatory drug-induced gastrointestinal toxicity, identification of groups at
      highest risk for development of nonsteroidal anti-inflammatory drug-induced
      gastrointestinal complications, recognition of co-therapies that could reduce
      nonsteroidal anti-inflammatory drug toxicity, and, most recently, development of
      classes of nonsteroidal anti-inflammatory drugs with improved gastrointestinal
      safety profiles. Many of these advances have occurred during the last year. This
      review focuses on several of the important recent observations that have improved
      understanding and safety of nonsteroidal anti-inflammatory drugs in the
      gastrointestinal tract.

PMID- 17031211
TI  - Gastroduodenal disorders in children.
AB  - The North American Society for Pediatric Gastroenterology and Nutrition published
      guidelines for the evaluation of children suspected of being infected with
      Helicobacter pylori. The stool antigen test for H. pylori, which was recently
      commercialized in the United States, was evaluated in two high-risk pediatric
      populations. The results are encouraging but should be interpreted with caution.
      A number of studies suggest that delayed gastric emptying may accompany a variety
      of disorders, or may be a cause of vomiting. The outcome of children with
      dyspeptic symptoms is described, and the results will be helpful in reassuring
      anxious parents. Studies examining the development of H, K-adenosine
      triphosphatase in infants and the role of enteric glial cells in infantile
      hypertrophic pyloric stenosis are discussed. A study of neonates with allergic
      gastroenteropathy suggests that this disorder may be more common in this age
      group than generally thought.

PMID- 17031212
TI  - Nonulcer dyspepsia.
AB  - Therapy for nonulcer dyspepsia has largely been empiric because effective
      therapeutic agents are sparse and therapeutic trials show inconsistent results.
      The Cochrane collaboration has reviewed this matter and came to the conclusion
      that prokinetics and acid-suppression therapy might have a significant, although
      small, clinical benefit over placebo. Although the role of Helicobacter pylori in
      nonulcer dyspepsia is still a matter of controversy, one meta-analysis suggests
      that in H. pylori-positive dyspeptic patients, H. pylori eradication has a small
      but significant therapeutic benefit over a therapy that does not eradicate H.
      pylori. Other aspects of pathophysiology of nonulcer dyspepsia that have been
      studied in the past year include visceral hyperalgesia and abnormal sleep
      pattern. New studies have also investigated the clinical presentation of nonulcer
      dyspepsia and the possible reasons why some patients never consult a doctor
      whereas others do so frequently.

PMID- 17031213
TI  - Interventional endoscopy.
AB  - Interventional endoscopy is a general label given to endoscopic procedures used
      to deal with a variety of gastrointestinal disorders. The interventional
      endoscopic procedures of interest in this review are those used specifically with
      gastric disorders. They include hemostasis, endoscopic ultrasound, endoscopic
      mucosal resection, stenting, percutaneous endoscopic gastrostomy tube placement
      and photodynamic laser therapy. Here, we review the latest data related to (a) a
      number of general issues having an impact on this diverse group of procedures
      (eg, such as proper patient selection criteria, consent in the era of open access
      endoscopy, protocol for anticoagulation, and sedation); (b) the methodology and
      outcomes of each of these unique procedures as they apply to the stomach; and (c)
      some of the latest technologic advances and developments that will potentially
      have an impact the future use of these procedures.

PMID- 17031214
TI  - Gastric surgery.
AB  - Significant advances in the role of gastric surgery in the management of disease
      in the past year have focused on three broad areas: morbid obesity, gastric
      cancer, and peptic ulcer disease. Although vertical banded gastroplasty and Roux
      en-Y gastric bypass are the two procedures most commonly used in the United
      States to induce weight loss in the morbidly obese patient, long-term follow-up
      continues to support the durability of the gastric bypass in maintaining a
      sustainable outcome with a minimum of complications. It is not surprising,
      therefore, that increasing interest has accrued in simplifying this operation and
      decreasing potential complications even further by employing laparoscopic
      technology. In the area of gastric cancer, several reports have provided
      important new information regarding its pathogenesis, factors influencing long
      term survival, and strategies for management when diagnosed early. Finally, in
      patients developing the complications of peptic ulcer disease (eg, obstruction
      and perforation), conservative management has been emphasized over more radical
      traditional approaches. This review highlights these advances.

PMID- 17031216
TI  - Update on immunologic basis of celiac disease.
AB  - During the past few years several seminal studies have greatly expanded our
      knowledge on celiac disease pathogenesis. This review focuses on aspects that
      have been most properly addressed and where substantial new information has been
      gathered include. Topics covered include (a) the identification of T-cell
      epitopes in gluten and the mechanisms of specific T-cell response in celiac
      disease small intestine; (b) the mechanisms of induction of mucosal lesion; and
      (c) the putative role of non-T-cell factors in driving mucosal response to
      gliadin. After discussing a brief history of the "quest for the cause of celiac
      disease," we examine the development of the typical celiac lesion (the crypt
      hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of
      dietary antigens; the early changes, linked to specific components of the innate
      immunity rather than to its adaptive branch; the most thoroughly investigated
      subsequent response, involving a strong T-cell response and cytokines; and the
      factors responsible for enterocytes' death. The emerging pattern is that of a
      complex interaction of factors, although far from being completely understood,
      but fascinating as it opens an incredible window of knowledge on an autoimmune
      disorder whose environmental factor is known, whose autoantigen is known, whose
      autoantibodies are known: a truly unique situation in medicine.

PMID- 17031217
TI  - Gastrointestinal manifestations of primary immunodeficiencies.
AB  - Congenital immunodeficiencies are relatively rare disorders that result in a
      marked predisposition to infection and to a variety of gastrointestinal problems.
      Increasingly recognized in both children and adults, accumulating worldwide
      experience with these disorders reveals that the long-term prognosis is poor in
      many cases, despite available treatments. This review highlights the past year's
      advances concerning the molecular basis of several of these disorders, new
      diagnostic considerations, and novel therapeutic approaches concerning their
      gastrointestinal complications. The availability of molecular diagnostic tools
      increases the options for earlier definitive treatments such as bone marrow
      transplantation and somatic gene therapy.

PMID- 17031218
TI  - Induction of mucosal immune responses by bacteria and bacterial components.
AB  - Bacteria have well documented abilities to induce protective as well as
      pathogenic mucosal immune responses, with the type of response dependent on the
      genetically programmed balance of pro- and anti-inflammatory cytokines and T
      lymphocyte subsets. Inflammatory bowel disease, especially Crohn disease and
      periodontal disease, appear to be overly aggressive cellular immune responses to
      some, but not all, normal resident bacteria. Recent evidence suggests that the
      balance of protective (probiotic) and aggressive commensal luminal bacterial
      species is an additional determinant of mucosal homeostasis (tolerance) versus
      pathogenic immune responses (loss of tolerance) and that this balance can be
      therapeutically manipulated. Mucosal pathogens elicit a characteristic profile of
      cytokines from epithelial cells, including chemokines that recruit effector cells
      to the site of invasion to clear the invading organism. The molecular mechanisms
      of epithelial attachment and invasion of bacterial pathogens (eg, Salmonella,
      Shigella, pathogenic Escherichia coli, and Yersinia) and the mechanisms of injury
      induced by Clostridium difficile toxins and Helicobacter pylori are beginning to
      be understood, as are the innate and cognate host immune responses to these
      organisms, leading to novel means to effectively block bacterial injury and
      induce protective immune responses through immunization.

PMID- 17031219
TI  - Autoimmune hepatitis.
AB  - Autoimmune liver disease encompasses several disorders (Table 1). Autoimmune
      hepatitis (AIH) affects mainly women and is characterized histologically by a
      portal tract mononuclear cell infiltrate disrupting the limiting plate and
      invading the parenchyma ("interface hepatitis") and serologically by the presence
      of autoantibodies and increased levels of immunoglobulin G (IgG), in the absence
      of a known cause. AIH responds to immunosuppressive treatment. It can present
      insidiously or as an acute hepatitis. The previously accepted requirement of 6
      month duration of symptoms before diagnosis can be made has been abandoned and
      treatment should be instituted as soon as the disease is diagnosed. In this
      review, we concentrate on those reports that add to our knowledge in terms of
      pathogenesis, differential diagnosis, treatment, and clinical course. Special
      attention is given to overlap syndromes.

PMID- 17031220
TI  - Role of innate immunity in cancer.
AB  - Recently, much progress has been made in the field of tumor immunology. Much of
      this work has focused on understanding and exploiting the innate immune response
      to tumor cells. A novel human receptor-ligand system that mediates natural killer
      (NK) and gammadelta T-cell killing of carcinoma cells has been identified, and
      the functions of an equivalent system in mice are beginning to be explored. The
      mechanisms of action of an innate tumoricidal cytokine, tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL), and of tumor cell resistance to it,
      are emerging, as are the ways in which tumor cells evade the damaging effects of
      IFN-gamma and of complement. Overcoming tumor cell resistance to innate immune
      attack could prove to be a fruitful approach to cancer immunotherapy in the
      clinic.

PMID- 17031221
TI  - Mucosal barrier and immune mediators.
AB  - The intestinal mucosa functions is an immunologic organ that plays a major role
      in the development of oral tolerance and host-defense mechanisms. Antigens must
      cross the intestinal epithelium in a controlled manner to interact with dendritic
      antigen-presenting cells, because bacteria or their products are a primary risk
      factor for the development of intestinal inflammation. Therefore, the regulation
      of the intestinal epithelial cell barrier is central to the development of
      intestinal immunity and inflammation, but the involved mechanisms are largely
      unknown. Intestinal barrier function relies on the formation of tight junctions
      at the apical contact areas of intestinal epithelial cells. Tight junctions have
      a highly dynamic structure whose permeability, assembly, or disassembly can be
      regulated by a variety of cellular and metabolic mediators, including cytokines,
      which have major functions in the immune system. Immune modulators control tight
      junction dependent intestinal barrier function during development, wound healing,
      and pathologic processes such as cancer, infection, and chronic inflammation.

PMID- 17031223
TI  - Campylobacter infection: small bowel and colon.
AB  - The important contribution of Campylobacter infections to human enteric disease
      is well established. Recent completion of the genomic sequence of a Campylobacter
      jejuni strain has heralded a renaissance in the field of Campylobacter
      pathogenesis research. With the application of novel, powerful technologies, our
      understanding of how these organisms mediate disease is set to evolve rapidly
      from its current, relatively neglected status.

PMID- 17031224
TI  - Update on protozoan parasites of the intestine.
AB  - The last year has seen new approaches to the diagnosis, treatment, and prevention
      of protozoal infections of the gastrointestinal tract. Some of the news is not
      good: new foodborne and swimming pool outbreaks of cyclosporiasis and
      cryptosporidiosis, respectively, occurred in North America; paromomycin was shown
      to be ineffective treatment for cryptosporidiosis; and these parasitic diseases
      continued to have a worldwide impact on human health. On the bright side, there
      were important advances in the understanding of the pathogenesis of
      cryptosporidiosis and the diagnosis of amebiasis and giardiasis, and some new
      leads on the treatment of cryptosporidiosis and refractory giardiasis. Finally,
      evidence was found of acquired mucosal immunity to amebiasis in Bangladeshi
      children, offering a guide for the development of an amebiasis vaccine. This
      review is not intended to be comprehensive, but contains a variety of articles
      that the authors hope will be of interest to the reader.

PMID- 17031225
TI  - Helicobacter pylori infection: pathogenesis.
AB  - Helicobacter pylori is known to be the cause of most gastric diseases, including
      both peptic ulcer disease and gastric cancer. In the absence of eradication,
      infection tends to be lifelong and the immune response ineffective in clearing
      the bacteria. A number of groups have investigated whether the immune clearance
      of infection can be achieved through a vaccination strategy, but to date, the
      results have been inconclusive. In fact, in most cases of natural infection, the
      host immune response leads to a chronic inflammation within the gastric mucosa
      that actually promotes the development of atrophy and neoplasia. In most cases,
      eradication of the organism leads to resolution of inflammation, which in many
      instances can result in reduction in atrophy and gastric cancer risk. This
      finding suggests that even at late stages, cancer progression is dependent, to a
      large extent, on infection/immune response. Work from a number of laboratories
      has led to the hypothesis that T-cells and the Th1 immune response, governed
      largely by host genetic factors, are strongly associated with the H. pylori
      mediated induction of atrophy and cancer. Interleukin-1beta appears to be a
      particularly important cytokine that inhibits acid secretion and increases serum
      gastrin levels, factors strongly associated with cancer induction. The induction
      by H. pylori of cytokines and chemokines and growth-related genes is mediated by
      the MAPK and NF-kappaB signaling pathway. Recent studies have shown that NF
      kappaB is activated through a NF-kappaB-inducing kinase/p21-activated kinase 1
      pathway. H. pylori can also promote cellular apoptosis through a number of
      mechanisms, the most important of which is upregulation of the Fas/FasL pathway.
      Finally, understanding of H. pylori pathogenesis has been broadened and deepened
      by the application of genomics and proteomics to the organism.

PMID- 17031226
TI  - Helicobacter pylori infection: treatment.
AB  - Current standard treatment regimens for Helicobacter pylori infection provide
      eradication rates 80 to 90%. These rates have been achieved with a variety of 1
      week triple therapies using two antibiotics and an acid suppressant. Antibiotic
      resistance, which may develop during failed treatment, is becoming increasingly
      common and has led to studies of new regimens for primary therapy, and new
      strategies for salvage of failed therapy. Other regimens have been designed and
      tested with the aim of decreasing the cost of initial therapy or to improve
      compliance, but abbreviated regimens have high incidence of failure and may add
      to the problem of resistance. Increasing attention has been paid to the need for,
      and timing of, the determination of antibiotic resistance of H. pylori isolates
      either at the time of initial diagnosis or after treatment failure. New, simpler,
      and noninvasive methods are offered for follow-up to determine if eradication has
      been successful. Treatment regimens should be chosen based on local drug
      susceptibility patterns and the availability of approved therapeutic agents in
      each country. Established indications for testing for H. pylori and administering
      therapy include active or inactive peptic ulcer disease, mucosa-associated
      lymphoid tissue (MALT) lymphoma, as well as hyperplastic polyps, hyperplastic
      gastropathy, postendoscopic resection for gastric malignancy, and acute H. pylori
      gastritis. It is now largely accepted that noninvestigated dyspepsia is an
      indication for testing for and treating H. pylori, but that dyspeptic symptoms
      shown not to be associated with ulcer (nonulcer dyspepsia) do not now provide an
      indication for testing. Controversial or unresolved indications for testing and
      treating include planned use of chronic antisecretory therapy, planned use of
      nonsteroidal anti-inflammatory drugs, and use as a general approach to the
      prevention of gastric cancer.

PMID- 17031227
TI  - Gastrointestinal infections in the immunocompromised host.
AB  - Immunocompromised patients, including patients with AIDS, solid organ and bone
      marrow transplant recipients, patients with leukemia and lymphoma, patients with
      inherited immune deficiencies, and patients on immunosuppressive therapy for a
      variety of disorders, are at risk for infections-particularly opportunistic
      infections, which, by definition, do not infect the healthy host. All systems of
      the body, including the gastrointestinal tract, are susceptible. The esophagus,
      stomach, small intestine, and large intestine are sites of infection for viruses,
      bacteria, fungi, and protozoa. Symptoms can range in severity from fevers of
      unknown etiology to life-threatening hemorrhage and perforation. This review
      summarizes recent case reports, clinical studies, and reviews pertaining to
      pathogens that uniquely cause disease, more frequently cause disease, or cause
      more severe disease in the immunocompromised host than in the immunocompetent
      host.

PMID- 17031228
TI  - Role of probiotics in the treatment of intestinal infections and inflammation.
AB  - Despite the relative success of analogous approaches in soil, aquatic, and animal
      environments, the enhancement of human health through probiotic consumption has
      not been generally endorsed in modern medicine. Laboratory-based studies are
      elucidating the mechanisms that mediate the properties attributed to beneficial
      lactic acid bacteria and Saccharomyces species in vivo. This research is now
      providing fundamental evidence to support observations of adhesion of probiotic
      species to intestinal tissue, antimicrobial activities, and immunomodulation.
      Probiotics appear to have a promising future in the treatment of certain
      disorders. Rigorously performed, controlled, double-blinded trials will overcome
      doubts relating to efficacy in vivo and open avenues along which probiotic-based
      therapies will rapidly progress. As a result of our emerging understanding of
      microbial activities and gene expression in situ, novel strategies will combine
      complementary probiotic functionalities in the form of microbial consortia or
      genetically enhanced organisms. As scientific knowledge and biotechnologic
      proficiency advance at an accelerating pace, the requirement for informed
      legislation and for mechanisms of effectively delivering these therapies to the
      sites of their intended function may limit the applications of probiotics.

PMID- 17031229
TI  - Risk factors for waterborne enteric infections.
AB  - Risk factors for waterborne enteric infections are deduced primarily from
      outbreak surveillance data; however, in the United States, only a fraction of the
      estimated water-related outbreaks are reported through passive surveillance. In
      the past several years, advances in molecular detection techniques have furthered
      our knowledge about foodborne and waterborne causes of gastroenteritis, allowing
      the association of certain pathogens with biologic and exposure-related
      susceptibilities in their hosts. This article summarizes some of the recent data
      characterizing susceptibility to three common waterborne
      pathogens:Cryptosporidium, a protozoan; Norwalk-like virus; and the bacterium
      Escherichia coli O157:H7. The infectious dose of Cryptosporidium varies by
      several orders of magnitude by strain, and repeated low-level exposure in
      drinking water may be protective. Some people may be innately immune to Norwalk
      like virus, despite multiple exposures. A major risk factor for E. coli O157:H7
      infection is exposure to shallow groundwater sources contaminated with animal
      waste.

PMID- 17031231
TI  - Expression of lymphoid enhancer factor/T-cell factor proteins in colon cancer.
AB  - Molecular genetic analysis of colon cancers has established that the Wnt
      signaling pathway is involved in early tumor development. Mutation of midstream
      components can activate the pathway, making it independent of Wnt ligands and
      maintaining constant pressure to change target gene expression. The transcription
      factors that connect the pathway to target genes are members of the lymphoid
      enhancer factor/T-cell factor (LEF/TCF) family. The genes for two members of this
      family, TCF 7 and LEF 1, produce full-length forms that mediate Wnt signals and
      truncated dominant negative forms that limit Wnt signals and may function as
      growth suppressors. Results from studies of their expression in colon cancer
      suggests that because Wnt-linked cancers progress to malignancy, there may be a
      strengthening of the Wnt signal by selective expression of the activating forms
      of LEF/TCFs and a bias against suppressing, truncated forms.

PMID- 17031232
TI  - Hamartomatous polyposis syndromes: genetic pathways.
AB  - Hamartomatous polyposis syndromes are a group of clinically distinct but perhaps
      genetically related disorders in which the predominant finding is multiple
      hamartomatous polyps in the gastrointestinal tract. These syndromes are
      transmitted in an autosomal dominant fashion to offspring, but sporadic forms do
      exist in which the biological parents lack an identified germline mutation.
      Despite the nondysplastic histologic characteristics of their polyps, each
      hamartomatous syndrome carries an elevated risk for cancer at specific organ
      sites. Several genes have been identified as mutated in the germline from these
      syndromes, and they provide clues to the pathogenesis of the polyps and may
      explain some of the elevated cancer risk. Pathways involved in the hamartomatous
      syndromes include those of vascular endothelial growth factor, the transforming
      growth factor beta superfamily, and antagonizing the effects of Akt/protein
      kinase B.

PMID- 17031233
TI  - Epigenetics in colorectal cancer.
AB  - Malignant transformation is now known to require a series of molecular
      alterations that disrupt a limited number of pathways including autocrine and
      paracrine responses to growth factors, cell-cycle control, senescence, motility,
      and invasion. Studies on hereditary cancers have established genetic changes as
      the primary driving force for these molecular alterations. Recently, however, it
      has been recognized that epigenetic changes, defined as clonal changes in gene
      expression without accompanying changes in primary DNA coding sequence, can also
      be a driving force in neoplastic transformation, for selected genes, and in
      specific tumors. DNA methylation within gene promoters and associated alterations
      in histone acetylation appear primary mediators of epigenetic inheritance in
      cancer cells. In the large intestine, aberrant DNA methylation arises very early,
      initially in normal-appearing mucosa, and may be part of the age-related field
      defect observed in sporadic colorectal neoplasia. Aberrant methylation also
      contributes to later stages of colon cancer formation and progression through a
      hypermethylator phenotype termed cytosine phosphoguanosine (CpG) island
      methylator phenotype (CIMP), which appears to be a defining event in
      approximately half of all sporadic tumors. In sporadic colon cancer, CIMP has
      distinct epidemiologic and clinical features and is responsible for most cases of
      microsatellite instability related to hMLH1 inactivation. The recognition of
      epigenetic changes as a driving force in colorectal neoplasia opens new areas of
      research in disease epidemiology, risk assessment, screening, and treatment.

PMID- 17031234
TI  - The pathogenesis of Hirschsprung disease.
AB  - Hirschsprung disease is the most common congenital malformation of the enteric
      nervous system. Phenotypic expression is variable because of incomplete
      penetrance, and the pathogenesis is multifactorial. Although mutations of the RET
      tyrosine kinase gene remain the most commonly identified cause, there are now
      eight separate human gene loci identified whose mutations result in this disease.
      Analysis of these gene products in experimental animal models and cell systems
      has led to an increasing elucidation of the signaling pathways that are in
      operation during specific embryonic time stages and that direct the spatial
      arrangements and differentiation of enteric neuroblasts. Mutation analysis
      through in vitro cell expression studies has led to detailed descriptions of the
      affected microdomains of signal pathway receptors and the cellular pathogenesis
      of abnormal signaling that leads to apoptosis of developing neurons before the
      completion of enteric nervous system development. The full description of the
      pathogenesis of this disorder awaits the definition of new genetic loci, multiple
      gene interactions, and the acknowledgment of random events that may lead to
      aganglionosis of the distal bowel.

PMID- 17031235
TI  - Implementation of colorectal cancer screening: the challenge.
AB  - Colorectal cancer is the second leading cause of cancer death among men and women
      in the United States, and its incidence is increasing in other developed
      countries throughout the world. Efficacious and cost-effectiveness screening
      measures exist for colorectal cancer, but successful implementation at a
      community level remains challenging. This article is a summary of recently
      published information on cost-effectiveness of colorectal screening, attempts to
      enhance acceptance and compliance by physicians and the public, and legislative
      efforts to ensure access to screening.

PMID- 17031236
TI  - Endoscopic treatment of lower gastrointestinal bleeding.
AB  - Urgent colonoscopy has emerged as the initial diagnostic and main therapeutic
      tool in the evaluation and treatment of colonic lower gastrointestinal bleeding.
      Endoscopic therapy can effectively treat most cases of colonic bleeding with a
      demonstrable improvement in clinical outcome parameters. The identification of
      high-risk stigmata of hemorrhage enables selective targeting of endoscopic
      therapy to lesions at high risk of rebleeding. Advances in technologies such as
      novel mechanical methods of hemostasis (eg, metallic clips), injection techniques
      (eg, cyanoacrylate injection), and the widening application of established
      endoscopic hemostatic techniques (eg, rubber-band ligation) to colonic lesions
      offers the possibility of further improvements in the efficacy of endoscopic
      hemostasis. Clinical trials are needed to compare these novel endoscopic
      techniques with more conventional approaches to establish the best form of
      endoscopic therapy for different bleeding lesions and finally to establish more
      definitively the optimal timing of colonoscopy.

PMID- 17031237
TI  - Update on immunologic basis of celiac disease.
AB  - During the past few years several seminal studies have greatly expanded our
      knowledge on celiac disease pathogenesis. This review focuses on aspects that
      have been most properly addressed and where substantial new information has been
      gathered include. Topics covered include (a) the identification of T-cell
      epitopes in gluten and the mechanisms of specific T-cell response in celiac
      disease small intestine; (b) the mechanisms of induction of mucosal lesion; and
      (c) the putative role of non-T-cell factors in driving mucosal response to
      gliadin. After discussing a brief history of the "quest for the cause of celiac
      disease," we examine the development of the typical celiac lesion (the crypt
      hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of
      dietary antigens; the early changes, linked to specific components of the innate
      immunity rather than to its adaptive branch; the most thoroughly investigated
      subsequent response, involving a strong T-cell response and cytokines; and the
      factors responsible for enterocytes' death. The emerging pattern is that of a
      complex interaction of factors, although far from being completely understood,
      but fascinating as it opens an incredible window of knowledge on an autoimmune
      disorder whose environmental factor is known, whose autoantigen is known, whose
      autoantibodies are known: a truly unique situation in medicine.

PMID- 17031238
TI  - Bibliography current world literature.

PMID- 17031239
TI  - Colorectal cancer screening, comorbidity, and follow-up in elderly patients.
AB  - OBJECTIVE: We examined the relationship between comorbid disease and performance
      of complete colon examination by colonoscopy or double contrast barium enema
      (DCBE) after positive screening fecal occult blood test (FOBT) in patients 70
      years of age or older. BACKGROUND: FOBT is an accepted form of colorectal cancer
      (CRC) screening. Factors that influence follow-up of positive FOBT have been
      largely unknown. METHODS: Patients aged 70 years and older with positive FOBT
      between March 1, 2000 and Feb 28, 2001 were included in this retrospective
      medical record review performed at a single center. Comorbidity was measured by
      the Charlson Comorbidity Scale. RESULTS: : In our sample of 266 subjects, 193
      (73%) were referred for evaluation of positive FOBT and 109 (41%) underwent a
      colonoscopy or DCBE within 12 months. Using the Charlson score for comorbidity,
      27% of our sample scored 0, 24% scored 1, and 23% scored 2 while 26% had a
      Charlson score of 3 or higher. There was no association between Charlson score
      (0, 1, 2, and > or =3) and referral for evaluation (chi test, P = 0.28) or
      performance of a complete colon examination (chi test, P = 0.38). CONCLUSIONS: In
      this sample, only 41% of patients with positive FOBT underwent a full colon
      examination within 12 months of a positive FOBT. Although comorbidity burden was
      considerable, there was no association between comorbidity score and referral for
      or performance of a full colon examination. These results suggest that
      inappropriate patients receive CRC screening, which may contribute to delays for
      screening appropriate patients and diagnostic delays for others with positive
      screening test findings.

PMID- 17031240
TI  - Cardiac autonomic dysregulation in patients with acute hepatitis.
AB  - BACKGROUND: Autonomic dysfunction is common in patients with chronic liver
      disease, but it is still unclear whether acute hepatitis coincides with
      alterations in autonomic functions. METHODS: We evaluated the heart rate
      variability (HRV) of 10 patients with acute hepatitis (6 males, 4 females; mean
      age, 44.0 y; range, 20-69 y). Frequency-domain analysis of short-term and
      stationary R-R intervals was performed on the first day of admission to detect
      low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz),
      the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). The same
      measurement was repeated on the 7th day of admission. RESULTS: We found that
      there was a significant increase of HF as well as variance of the R-R interval on
      the 7th day after admission (P < 0.05). There was a significant negative
      correlation between HF and the change of total bilirubin (P < 0.05). CONCLUSIONS:
      The study demonstrates a change in cardiac vagal tone associated with acute
      hepatitis by analysis of HRV, and such alteration is less pronounced later during
      the clinical course of acute hepatitis.

PMID- 17031241
TI  - Chlamydophila (Chlamydia) pneumoniae infection of human astrocytes and microglia
      in culture displays an active, rather than a persistent, phenotype.
AB  - BACKGROUND: The intracellular pathogen Chlamydia pneumoniae can cause persistent
      infections during which its morphologic, molecular, and pathogenic
      characteristics differ importantly from those of active infection. This bacterium
      was identified within astrocytes and microglia in the brain of late-onset
      Alzheimer disease patients. We investigated whether infection of these two host
      cell types displays an active or persistent growth phenotype. METHODS: The human
      astrocytoma and microglioma cell lines U-87 MG and CHME-5 (respectively) and the
      human epithelial cell line HEp-2 were infected by the standard method with C
      pneumoniae strain AR-39. Cultures were harvested at 24, 48, and 72 hours
      postinfection and subjected to analysis of inclusion morphology. DNA and RNA were
      prepared from portions of each infected culture sample and analyzed for relative
      chromosome accumulation and presence or absence of several specific bacterial
      mRNAs. RESULTS: Astrocytes and microglial cells infected in vitro with C
      pneumoniae displayed inclusions that were indistinguishable from those
      characteristic of active infection of the standard HEp-2 host cell line. Real
      time polymerase chain reaction (PCR) showed that the relative accumulation of
      chlamydial chromosome over time during infection of these two cell lines also was
      virtually identical to that in actively infected HEp-2 cells. Reverse
      transcriptase PCR (RT-PCR) analyses showed that mRNA from ftsK, pyk, and other
      chlamydial genes whose expression is abrogated during persistent infection were
      easily identifiable in infected CHME-5 and U-87 MG cells. CONCLUSIONS: In
      cultured human astrocytes and microglia, C pneumoniae displays an active, not a
      persistent, growth phenotype. This indicates normal passage through the
      developmental cycle with its probable concomitant destruction by lysis of some
      portion of host cells at the termination of that cycle.

PMID- 17031242
TI  - The clinical impact of bacteremia in complicated acute pyelonephritis.
AB  - BACKGROUND: Bacteremia has been considered as a surrogate marker of severe
      infection in several infectious diseases. However, it remains uncertain whether
      the presence of bacteremia correlates with severe infection in patients with
      complicated acute pyelonephritis (APN). METHODS: We performed a retrospective
      study to investigate the relationship between the presence of bacteremia and
      disease severity in complicated APN. To do this, we reviewed medical records from
      128 patients diagnosed with complicated APN admitted to Kaohsiung Veterans
      General Hospital, Taiwan between January, 2003 and December, 2003. In our
      analysis, we compared clinical presentation, treatment response, and outcome in
      patients with and without bacteremia. RESULTS: Fifty-four of 128 patients (42%)
      were bacteremic. This group of patients presented more frequently with severe
      sepsis or septic shock (P < 0.001), compared with nonbacteremic patients. Other
      factors that correlated with the presence of bacteremia were older age, diabetes
      mellitus, more band forms in neutrophil cell counts, impaired renal function, and
      a lower level of serum albumin. Using a multivariate logistic regression
      analysis, we show that lower levels of serum albumin (odds ratio, 0.18; 95% CI,
      0.05-0.65; P = 0.008) and presence of severe sepsis (odds ratio, 4.76; 95% CI,
      1.43-15.84; P = 0.011) were independent factors associated with bacteremia.
      Following treatment, the bacteremic group took a longer time to become
      defervescent than the nonbacteremic group (5.1 +/- 2.3 vs. 4.2 +/- 1.6 days, P =
      0.023). Also, the bacteremic group had a greater mean duration of intravenous
      antibiotics administration and longer hospital stays (P < 0.001). Multiple
      logistic regression analysis shows that non-Escherichia coli bacteremia, presence
      of urolithiasis or hydronephrosis, shorter duration of antibiotics
      administration, and being male were significantly associated with recurrence of
      urinary tract infection within 6 months. CONCLUSION: Bacteremia in cases of
      complicated APN indicates a severe disease, which is more likely to recur in
      patients with non-E coli bacteremia. Our study showed that bacteremia is indeed a
      useful clinical indicator of severe disease and, if found, should influence
      patient management. Therefore, we recommend that blood culture samples should be
      taken in all patients with complicated APN.

PMID- 17031243
TI  - Effects of histologic type on levels of macrophage colony-stimulating factor in
      liquid contents of benign ovarian tumors.
AB  - BACKGROUND: Normal ovarian tissue is rich in cytokines. Cytokines are important
      in the physiology of ovarian function. Most of the same cytokines that are found
      in normal ovarian tissue are also found in association with benign and malignant
      tumors in contrast to their functions in normal tissues. Thus, we measured
      macrophage colony-stimulating factor (M-CSF) levels in the liquid contents of
      benign ovarian tumors--serous cystadenoma, mucinous cystadenoma, and mature
      cystic teratoma--and investigated whether M-CSF levels were associated with the
      histologic type of the ovarian tumors. METHODS: We enrolled 65 patients, 52 with
      benign ovarian tumor and 13 in the early postmenopausal period with symptoms of a
      menopausal disorder. Among the 52 patients with benign ovarian tumor, 16 had
      serous cystadenoma, 21 had mucinous cystadenoma, and 15 had mature cystic
      teratoma. Immediately after surgery, the liquid content was drawn from the
      ovarian tumor, then centrifuged, and the separated supernatant was stored at -30
      degrees C. The M-CSF level was determined by the sandwich enzyme-linked
      immunosorbent assay method with use of three antibodies. RESULTS: The level of M
      CSF was 12,513 U/mL (median) (range, 0-169,000 U/mL) in serous cystadenoma, 915
      U/mL (0-82,500 U/mL) in mucinous cystadenoma, and 149 U/mL (0-6,230 U/mL) in
      mature cystic teratoma. The M-CSF levels increased significantly from mature
      cystic teratoma to mucinous cystadenoma to serous cystadenoma. The serum M-CSF
      levels were 308 to 499 U/mL in patients with benign ovarian tumor. The M-CSF
      levels did not differ significantly among the three groups. The serum M-CSF
      levels were 162 U/mL (0-473 U/mL) in menopausal patients. CONCLUSIONS: Elevation
      of levels of M-CSF varies according to histologic type in benign ovarian tumors.
      This implies that the antitumor activities of M-CSF for serous cystadenoma,
      mucinous cystadenoma, and mature cystic teratoma differ by histologic type.

PMID- 17031244
TI  - Biomarkers in cardiovascular disease: integrating pathophysiology into clinical
      practice.
AB  - Biomarkers play an important role in the diagnosis, prognostic assessment, and
      management of patients with suspected acute coronary syndromes (ACS). Specific
      biomarkers identify different components of the pathophysiology of ACS: troponins
      are prototype markers of myocyte necrosis, natriuretic peptides reflect
      neurohormonal activation and hemodynamic stress, soluble CD40 ligand is an
      indicator of platelet activation, and C-reactive protein, myeloperoxidase, and
      monocyte chemoattractant protein-1 reflect various inflammatory processes. When
      combined, multiple biomarkers reflecting different pathophysiologic processes
      appear to enhance risk stratification, as compared with using individual markers
      alone. Advances in proteomic technology promise to identify additional novel
      biomarkers that facilitate diagnosis, risk stratification, and selection of
      therapies in ACS. In the future, it is hoped that multiple biomarker panels will
      form the basis of an individualized approach to the treatment of ACS, in which
      therapy is tailored to individual biomarker profiles.

PMID- 17031245
TI  - Pericardial involvement as an atypical manifestation of giant cell arteritis:
      report of a clinical case and literature review.
AB  - PURPOSE: Pericardial effusion has been known to be a rare manifestation of giant
      cell arteritis. During the last six decades, only 24 cases have been cited in the
      literature. In this report, we describe the case of a patient presenting with
      nonspecific symptoms and development of pericardial effusion. PROCEDURES AND
      FINDINGS: A 71-year-old woman was admitted to the hospital with low-grade fever,
      exertion breathlessness, atypical diffuse muscular pain, and weight loss over a
      period of about 5 weeks. Pericardial effusion and giant cell arteritis were
      diagnosed by echocardiography and left temporal artery biopsy, respectively.
      Treatment with corticosteroids resulted in remarkable improvement of symptoms and
      complete remission of pericardial effusion. One year after admission, the patient
      remained in a stable good condition, under low steroid maintenance dosage.
      CONCLUSIONS: The diversity of clinical manifestations (such as pericardial
      effusion) in such a potentially severe disease should alert the physician to
      prompt diagnosis and treatment in view of impending irreparable vascular damages,
      even in cases in which the initial presentation is quite uncommon.

PMID- 17031246
TI  - Pregnancy-induced pancytopenia with cellular bone marrow: distinctive hematologic
      features.
AB  - Three patients with pregnancy-induced pancytopenia also exhibited variable
      features of sideroblastic anemia and amegakaryocytic thrombocytopenia. Treatment
      with anti-thymocyte globulin proved highly effective in two cases and a
      spontaneous remission occurred in the third. This illness is distinct from the
      more commonly reported incidental association of pregnancy with classic aplastic
      anemia. Its differentiation from myelodysplasia is also emphasized.

PMID- 17031247
TI  - Myocardial involvement in rocky mountain spotted fever: a case report and review.
AB  - Rocky Mountain Spotted Fever (RMSF), caused by Rickettia rickettsii, is a serious
      tickborne illness that is endemic in the southeastern United States. Although it
      is most commonly known as a cause of fever and rash, it can have systemic
      manifestations. The myocardium may rarely be involved, with symptoms that can
      mimic those of acute coronary syndromes. This report describes a case of
      serologically proven RMSF causing symptomatic myocarditis, manifested by chest
      pain, elevated cardiac enzyme levels, and decrease myocardial function. After
      treatment with antibiotics, the myocarditis resolved. Thus, although unusual, the
      clinician should be aware of myocardial disease in patients with appropriate
      exposure histories or other clinical signs of RMSF. Close monitoring and an
      aggressive approach are essential to reduce mortality rates.

PMID- 17031248
TI  - The impact of lifestyle behavior on hypertension awareness, treatment, and
      control in a southeastern population.
AB  - BACKGROUND: We were interested in determining the rates of hypertension
      awareness, treatment, and control in individuals living in the southeastern
      United States and evaluating the impact of lifestyle behaviors on these rates.
      METHODS: This is a cross-sectional survey of a sample of community dwellers in
      the greater Columbia, South Carolina area. The survey was developed from
      validated community-based survey questionnaires to evaluate demographic and
      social history (age, gender, race-ethnicity, income, and education), hypertension
      history (diagnosis and treatment), and lifestyle behavior (servings of fruits and
      vegetables [FV] and physical activity [PA] duration and frequency), as well as
      blood pressure measurement. RESULTS: A total of 763 people (mean +/- standard
      error age 52.4 +/- 0.7 years; 68% women, 53% African American) agreed to be
      screened. Of all participants with hypertension (438 [58%]), 82% were aware of
      their illness and 79% were on treatment. Of all hypertensive participants, 39%
      had their hypertension controlled below 140/90 mm Hg at the time of the survey.
      Only 11% reported consuming five or more FV per day and 18% reported PA five or
      more times per week. African-Americans consumed less FV (P < 0.001) and performed
      less PA (P < 0.001). Those consuming more FV and exercising more frequently had
      lower hypertension prevalence and tended to have better control rates.
      CONCLUSIONS: In a sample of southeastern residents, the control rate was
      suboptimal despite a relatively high rate of treatment. Low levels of FV
      consumption and PA were noted especially in African-American patients and may
      explain this rate.

PMID- 17031249
TI  - Vibrio vulnificus bacteremia associated with chronic lymphocytic leukemia,
      hypogammaglobulinemia, and hepatic cirrhosis: relation to host and exposure
      factors in 252 V. vulnificus infections reported in Louisiana.
AB  - BACKGROUND: Vibrio vulnificus infection in persons with B-chronic lymphocytic
      leukemia (B-CLL) or hypogammaglobulinemia has been reported infrequently. PATIENT
      AND METHODS: A woman with B-CLL, hypogammaglobulinemia, and hepatic cirrhosis
      died of V. vulnificus bacteremia after eating cooked shrimp and crabs. We
      reviewed host and exposure data in 252 cases of V. vulnificus infection reported
      in Louisiana during the interval of 1980 through 2004. RESULTS: V. vulnificus was
      isolated from blood in 122 cases (48.8%). Preexisting conditions in 138 cases
      included liver disease (41.3%), malignancy (13.8%), and immunosuppression (9.4%).
      The prevalence of preexisting conditions was significantly greater in cases with
      positive blood cultures than in cases with positive wound or stool cultures.
      Exposure data in 116 cases revealed crab consumption without raw oyster
      consumption or seawater exposure in 3.4%. CONCLUSION: The present patient had
      several conditions associated with increased risk of V. vulnificus infection and
      bacteremia, especially hepatic cirrhosis, but her route of exposure to V.
      vulnificus was unusual.

PMID- 17031250
TI  - ACSM Fellow Ken Baldwin and colleagues discover a new antisense retrograde
      mechanism of gene regulation.

PMID- 17031251
TI  - Muscle reflexes in motion: how, what, and why?
AB  - Methods have been developed to study excitatory and inhibitory reflexes during
      human movements because dramatic task-dependent changes occur between different
      voluntary activities, and phase-dependent changes occur within cyclic movements.
      Interestingly, segmental reflexes are relatively unimportant for standing
      balance, although reflex responses are strong, yet they contribute substantially
      to force in several muscles during walking, when some reflex responses are
      weaker.

PMID- 17031252
TI  - Neural aspects of muscle stretching.
AB  - Neural mechanisms contribute significantly to the gains that occur in the range
      of motion about a joint with stretching exercises. In the acute condition,
      lengthening of a muscle-tendon unit decreases spinal reflex excitability, which
      reduces passive tension and increases joint range of motion. Similarly,
      participation in a stretch-training program decreases tonic reflex activity and
      increases flexibility.

PMID- 17031253
TI  - The molecular physiology of human limb immobilization and rehabilitation.
AB  - This short review will identify some of the molecular signaling events that
      regulate atrophy during immobilization in human skeletal muscle and how
      prescribed exercise rehabilitation may influence these signaling events. The
      potential for nutritional intervention to positively modulate molecular signaling
      and thereby offset muscle wasting and/or accelerate rehabilitation in humans will
      also be considered.

PMID- 17031254
TI  - Muscle perfusion and metabolic heterogeneity: insights from noninvasive imaging
      techniques.
AB  - Recent developments in noninvasive imaging techniques have enabled the study of
      local changes in perfusion and metabolism in skeletal muscle as well as patterns
      of heterogeneity in these variables in humans. In this review, the principles of
      these techniques along with some recent findings on functional heterogeneity in
      human skeletal muscle will be presented.

PMID- 17031255
TI  - PGC-1alpha gene and physical activity in type 2 diabetes mellitus.
AB  - Exercise stimulates PGC-1alpha gene expression and increases V O2max, the latter
      of which relates inversely with type 2 diabetes risk. Consistently, low levels of
      PGC-1alpha mRNA and nucleotide sequence variation at PGC-1alpha associate with
      lower level of V O2max and increased diabetes risk. Thus, PGC-1alpha sequence
      variation may interact with physical activity to modify diabetes risk via changes
      in oxidative energy metabolism.

PMID- 17031256
TI  - Toll-like receptor 4: link to the anti-inflammatory effects of exercise?
AB  - Evidence is emerging that exercise training has anti-inflammatory effects. Our
      early finding that blood cultures from trained subject had a reduced
      responsiveness to lipopolysaccharide led to a series of studies in which we
      measured toll-like receptor 4--the primary signaling receptor for
      lipopolysaccharide. The toll-like receptor 4 expression was consistently lower in
      physically active subjects compared with inactive subjects and reduced after
      training in previously inactive subjects.

PMID- 17031257
TI  - Randomized controlled trials of physical activity and breast cancer prevention.
AB  - Observational studies demonstrate that women who exercise have a lower risk of
      developing breast cancer compared with sedentary women, but clinical trials are
      necessary to demonstrate a decreased effect of exercise on breast cancer. This
      review presents a rationale for randomized controlled exercise trials for breast
      cancer prevention and proposes a construct for designing such trials.

PMID- 17031258
TI  - Exercise-disordered breathing in chronic heart failure.
AB  - Patients with heart failure develop various ventilatory abnormalities, including
      reduced ventilatory reserves, increased ventilatory demands, and high work and
      cost of breathing. They tend to breathe with a rapid-shallow pattern, have low
      end-expiratory lung volumes, and may develop rhythmic oscillations in ventilation
      and tidal volume. These abnormalities likely contribute to exercise limitations
      and are associated with a worsening prognosis.

PMID- 17031259
TI  - Increased alveolar and plasma gelatinases activity during postpump syndrome:
      Inhibition by inhaled nitric oxide.
AB  - Postpump syndrome is associated with systemic inflammation. Matrix
      metalloproteinases (MMP)-2 and -9 contribute to proinflammatory and platelet
      activator reactions. Nitric oxide (NO) is involved in the regulation of MMPs. The
      objectives of our study were to investigate the intensity of inflammation induced
      by 3 different surgical procedures, the effects of inflammation on the activity
      of MMPs, and the regulation of inflammation by inhaled NO (20 ppm). Inhaled NO
      was initiated immediately after tracheal intubation and maintained for the total
      duration of the experiments. Thirty pigs were equally randomized into 6 groups
      [sham; sham + NO; cardiopulmonary bypass; bypass + NO; bypass +
      lipopolysaccharide (1 microg/kg for 50 min); bypass + lipopolysaccharide + NO]
      and animals were subjected to anesthesia and mechanical ventilation up to 24 h.
      The levels of MMP-2 and MMP-9 in plasma and bronchoalveolar lavage were measured
      using zymography. Bypass resulted in a time-dependent rise in MMP activity, an
      effect potentiated by lipopolysaccharide. Inhaled NO attenuated the effects of
      bypass + lipopolysaccharide. These results confirm that MMP-2 and MMP-9 are
      associated with the inflammatory process causing the postpump syndrome.
      Preemptive and continuous administration of inhaled NO helps to prevent increased
      MMP-2 and MMP-9 activity.

PMID- 17031260
TI  - Prevention of postischemic myocardial reperfusion injury by the combined
      treatment of NCX-4016 and Tempol.
AB  - Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion
      (I/R) injury. However, the concomitant production of superoxide and other
      reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO
      and hence compromise the beneficial effects. The objective of this study was to
      investigate the protective effect of the coadministration of NCX-4016 [2
      (acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester] (an NO donor) with
      antioxidants Tempol, superoxide dismutase (SOD), or urate on I/R injury. Isolated
      rat hearts, perfused with Krebs-Henseleit buffer, were subjected to 30 minutes of
      global ischemia, followed by 45 minutes of reperfusion. Before the induction of
      ischemia, the hearts were infused for 1 minute with NCX-4016 (100 microM) either
      alone or in combination with Tempol (100 microM), SOD (200 U/mL), or urate (100
      microM). Hearts pretreated with NCX-4016 showed a significantly enhanced recovery
      of function and decreased infarct size and LDH/CK release compared with the
      controls. However, treatment of hearts with NCX-4016 + Tempol, SOD, or urate
      showed a significantly enhanced recovery of heart function compared with NCX-4016
      alone. The treatment of hearts with NCX-4016 + Tempol showed significantly
      enhanced NO generation and decreased ROS and dityrosine (a marker of
      peroxynitrite) formation. In conclusion, NCX-4016 in combination with Tempol
      demonstrated significant cardioprotection and, thus, may offer a novel
      therapeutic strategy to prevent I/R-mediated myocardial injury.

PMID- 17031261
TI  - Oxidative stress-associated vascular aging is xanthine oxidase-dependent but not
      NAD(P)H oxidase-dependent.
AB  - Vascular aging is characterized by endothelial dysfunction that is primarily
      attributed to increased superoxide production, the exact source of which remains
      ambiguous. This study compared the NAD(P)H and xanthine oxidase (XO) systems as
      sources of superoxide and impaired vascular function in aging. Male Sprague
      Dawley rats, 4-months-old (young) and 18-months-old (Aging), were used. Systolic
      blood pressure was higher (36 +/- 3%) in the aging group compared with young
      rats, and this was accompanied by reduced acetylcholine-induced renal
      vasodilatation. Urinary excretion of nitrite was lower in the aging rats (P <
      0.05), and this was associated with reduced nitric oxide synthase (NOS) activity
      and reduced eNOS and iNOS protein expression in the aorta. Aged rats showed a n
      approximately twofold increase in free radical generation, as evident by
      increased plasma 8-isoprostane level, and an approximately fourfold increase in
      proteinuria compared with the young rats. Vascular NADP(H) oxidase was unchanged
      between both groups, as was the expression of p67phox or p47phox components of
      NAD(P)H oxidase. However, XO activity was increased (19 +/- 1%; P < 0.05) as well
      as XO expression in the aorta of aging rats. These results suggest that increased
      free radical generation-associated increase in SBP in aging rats is XO but not
      NAD(P)H oxidase-dependent.

PMID- 17031262
TI  - Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular
      remodeling and failure in diabetes-associated myocardial infarction.
AB  - Diabetes mellitus adversely affects the outcomes in patients with myocardial
      infarction (MI), due in part to the exacerbation of left ventricular (LV)
      remodeling. Although angiotensin II type 1 receptor blocker (ARB) has been
      demonstrated to be effective in the treatment of heart failure, information about
      the potential benefits of ARB on advanced LV failure associated with diabetes is
      lacking. To induce diabetes, male mice were injected intraperitoneally with
      streptozotocin (200 mg/kg). At 2 weeks, anterior MI was created by ligating the
      left coronary artery. These animals received treatment with olmesartan (0.1
      mg/kg/day; n = 50) or vehicle (n = 51) for 4 weeks. Diabetes worsened the
      survival and exaggerated echocardiographic LV dilatation and dysfunction in MI.
      Treatment of diabetic MI mice with olmesartan significantly improved the survival
      rate (42% versus 27%, P < 0.05) without affecting blood glucose, arterial blood
      pressure, or infarct size. It also attenuated LV dysfunction in diabetic MI.
      Likewise, olmesartan attenuated myocyte hypertrophy, interstitial fibrosis, and
      the number of apoptotic cells in the noninfarcted LV from diabetic MI. Post-MI LV
      remodeling and failure in diabetes were ameliorated by ARB, providing further
      evidence that angiotensin II plays a pivotal role in the exacerbated heart
      failure after diabetic MI.

PMID- 17031263
TI  - Rho kinase contributes to androgen amplification of renal vasoconstrictor
      responses in the spontaneously hypertensive rat.
AB  - Androgens modulate vascular tone and hypertension development. Rho kinase
      contributes to norepinephrine- (NE) and vasopressin- (AVP) induced
      vasoconstriction. This study tested the hypothesis that Rho kinase contributes to
      androgen amplification of renal vasoconstrictor responses to NE or AVP in
      isolated perfused kidney of spontaneously hypertensive rats (SHRs).SHRs (5 weeks)
      underwent sham operation, castration, or castration with testosterone
      replacement. At 16-17 weeks, mean arterial pressure and heart rate were measured
      in conscious SHRs. Renal vascular reactivity to NE (10 to 10 mol) and to AVP (10
      to 10 mol) was assessed in an isolated perfused kidney preparation before and
      after Rho kinase inhibitor treatment (fasudil; 15 microM). Castration reduced
      mean arterial pressure, whereas testosterone treatment of castrated SHRs
      increased mean arterial pressure significantly. The dose-response curves to NE
      and AVP obtained in isolated perfused kidneys from castrated SHRs were displaced
      to the right of those obtained in sham-operated and castrated + testosterone
      treated SHRs. Fasudil treatment produced a rightward shift in the dose-response
      curves for each agonist in all of the groups and greatly attenuated the
      differences in renal vascular reactivity to NE and AVP among the 3 groups of
      SHRs.Collectively, these findings indicate that androgen modulation of
      hypertension development in the SHR involves a fasudil-sensitive pathway and
      suggest that further study is warranted in this area.

PMID- 17031264
TI  - Effects of long-term oral dipyridamole treatment on coronary microcirculatory
      function in patients with chronic stable angina: A substudy of the persantine in
      stable angina (PISA) study.
AB  - AIMS: A meta-analysis of 13 randomized placebo-controlled trials demonstrated a
      benefit for dipyridamole therapy, particularly with longer duration of treatment.
      Although the mechanism of this effect is not well understood, dipyridamole
      increases endogenous tissue adenosine, which may have a beneficial effect on
      myocardial perfusion. Therefore, we measured the effects of dipyridamole on
      myocardial blood flow (MBF) and coronary flow reserve (CFR) by using positron
      emission tomography and H2O in patients with coronary artery disease. METHODS:
      Forty-four patients with angiographically documented coronary artery disease were
      double-blind randomized to either oral dipyridamole [200 milligrams (mg) twice
      daily (bd)] or placebo as add-on to conventional antianginal treatment for 24
      weeks. MBF was measured at rest and during dobutamine stress at baseline and
      study completion for the region subtended by the most severe coronary artery
      stenosis (Isc) and remote myocardium subtended by arteries with minimal or no
      disease (Rem). CFR was calculated as MBF-peak/MBF-rest. RESULTS: Thirty-five
      patients completed the study. Isc MBF-rest decreased in patients receiving
      dipyridamole (0.10 mL/minute/g; P = 0.03) and increased in the placebo group
      (0.16 mL/minute/g; P = 0.01) during the 24-week study. No significant change in
      MBF-peak was demonstrated in either group. Consequently, Isc-CFR increased
      significantly in patients receiving dipyridamole (1.65 +/- 0.47 vs 1.83 +/- 0.67;
      P < 0.05). By contrast, Isc-CFR decreased significantly in those receiving
      placebo (1.74 +/- 0.44 versus 1.38 +/- 0.46; P < 0.03). No change was seen in Rem
      CFR territories. CONCLUSIONS: At the end of treatment, a reduction in baseline
      MBF but no significant changes in hyperemic MBF were observed in ischemic
      myocardial territories, and therefore the significance of the observed
      improvement in CFR remains unclear.

PMID- 17031265
TI  - Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats.
AB  - Thyroid dysfunction produces marked cardiovascular responses. Hypothyroidism and
      hyperthyroidism cause important changes in the circulating renin-angiotensin
      system (RAS). Modifications in cardiac RAS have also been involved in
      cardiovascular alterations. Studies have revealed that thyroid hormones activate
      some components of cardiac RAS. Angiotensin (Ang) peptides are regulated by the
      activity of several aminopeptidases (AP) called angiotensinases. Previous results
      in our laboratory have demonstrated that thyroid dysfunction altered
      angiotensinase activities in hypothalamus, pituitary, and kidney. In the present
      study, we investigated the relationship between thyroid status and local
      angiotensinase activities in the atrium of hypothyroid, euthyroid, and
      hyperthyroid adult male rats. We have determined fluorometrically soluble and
      membrane-bound alanyl, glutamyl, and aspartyl aminopeptidase activities using
      naphthylamide derivatives as substrates. These activities have been,
      respectively, involved in the metabolism of Ang III to Ang IV, Ang II to Ang III,
      and Ang I to des-Asp Ang I. Hyperthyroidism was induced with subcutaneous
      injections of tetraiodothyronine (300 microg/kg/day), and the hypothyroid rats
      were obtained with 0.03% methimazole via the drinking water. Compared with that
      in euthyroid rats, a highly significant increase (by 50%) of soluble aspartyl
      aminopeptidase activity (P < 0.001) was observed in the atrium of hyperthyroid
      and hypothyroid animals. In membrane fractions, T4 treatment produced an increase
      in alanyl aminopeptidase (37%; P < 0.05) and aspartyl aminopeptidase activities
      (30%; P < 0.01). These results suggest higher formation of des-Asp Ang I in both
      hypothyroid and hyperthyroid rats but also suggest higher metabolism of Ang III
      to Ang IV in hyperthyroid animals, which is in agreement with the described
      alterations of cardiac RAS after thyroid dysfunction.

PMID- 17031266
TI  - Role of autonomic nervous activity in the antiarrhythmic effects of magnesium
      sulfate in a canine model of polymorphic ventricular tachyarrhythmia associated
      with prolonged QT interval.
AB  - This study was performed to examine the role played by the autonomic nervous
      system in the antiarrhythmic effects of magnesium sulfate (Mg) in a canine model
      of polymorphic ventricular tachyarrhythmia facilitated by anthopleurin-A and a
      slower heart rate induced QT interval prolongation. In 6 experiments, complete
      atrioventricular block was created to control the heart rate and bradycardia at
      800- to 1500-ms cycle lengths was applied for 60 sec before and after drug
      induced autonomic block. Transmural unipolar electrograms were recorded from
      multipolar needle electrodes, and activation-recovery intervals (ARI) were
      measured. Before drug-induced autonomic block, polymorphic ventricular
      tachyarrhythmia developed in all 6 experiments during bradycardia before but not
      after the administration of Mg (0.2 ml/kg intravenous bolus). During drug-induced
      autonomic block, triggered premature activity decreased without significant
      changes in underlying dispersion of repolarization and polymorphic ventricular
      tachyarrhythmia developed during bradycardia in 1 experiment. Administration of
      Mg during drug-induced autonomic block eliminated premature activity and
      polymorphic ventricular tachyarrhythmia during bradycardia. The distribution of
      left ventricular (LV) and right ventricular repolarization and dispersion of
      transmural repolarization were analyzed before and 60 sec after Mg administration
      during ventricular pacing at 80 bpm. Mg caused a modest shortening of ARI at all
      sites before and after drug-induced autonomic block. Since ARI shortening was
      greater at the mid-myocardial sites than at other LV sites, Mg decreased
      transmural ARI dispersion from 77 +/- 16 to 46 +/- 21 ms before drug-induced
      autonomic block and from 79 +/- 7 to 51 +/- 16 ms after drug-induced autonomic
      block. The antiarrhythmic effects of Mg in this model of long QT syndrome were
      attributable to its direct pharmacological properties and not to changes in
      ambient autonomic nervous activity. The blockade of sympathetic activity
      decreased the incidence of premature events and partially suppressed polymorphic
      ventricular tachyarrhythmia in this model.

PMID- 17031267
TI  - Direct effect of F12511, a systemic inhibitor of Acyl-CoA cholesterol
      acyltransferase on bovine aortic endothelial cells.
AB  - F12511(S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-alpha-phenylacetanilide
      (F12511) is a new Acyl-CoA cholesterol acyltransferase (ACAT) inhibitor that not
      only reduces the plasma cholesterol levels but also has anti-atherosclerotic
      actions in animals models. The study's aim was to analyze if F12511 may directly
      modify the ability of tumor necrosis factor--alpha (TNF-alpha)-incubated bovine
      aortic endothelial cells (BAEC) to express endothelial nitric oxide synthase
      (eNOS) protein and inflammatory-related proteins such as platelet endothelial
      cell adhesion molecule (PECAM) and CD40 ligand (CD40L). The addition of
      increasing concentrations of F12511 (10 to 10 mol/L) failed to modify the level
      of eNOS protein expressed in control BAEC. TNF-alpha (10 ng/mL) reduced the
      expression of eNOS protein. In TNF-alpha--incubated BAEC, F12511 protected eNOS
      expression in a concentration-dependent manner. TNF-alpha stimulated the
      expression of both CD40L and PECAM in cultured BAEC. F12511 (10 mol/L) failed to
      modify the expression of CD40L and PECAM in control and TNF-alpha-incubated BAEC.
      Reverse transcriptase polymerase chain reaction showed a marked expression of the
      ACAT-2 isoform and absent of expression of the ACAT-1 isoform in BAEC. The
      presence of ACAT-2 isoform in BAEC was further confirmed by Western blot. F12511
      failed to modify the expression of the proinflammatory associated proteins PECAM
      and CD40L in the endothelium but protected eNOS expression in the endothelial
      cells exposed to inflammatory conditions.

PMID- 17031283
TI  - Avastin and new treatments for AMD: where are we?

PMID- 17031284
TI  - Development of ranibizumab, an anti-vascular endothelial growth factor antigen
      binding fragment, as therapy for neovascular age-related macular degeneration.
AB  - BACKGROUND: Angiogenesis is a key aspect of the wet form of age-related
      neovascular (AMD), the leading cause of blindness in the elderly population.
      Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A
      is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is
      the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C,
      VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be
      generated due to alternative mRNA splicing. Various VEGF inhibitors have been
      clinically developed. Among these, ranibizumab is a high affinity recombinant Fab
      that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology
      of VEGF and then focuses on the path that led to clinical development of
      ranibizumab. RESULTS: The safety and efficacy of ranibizumab in the treatment of
      neovascular AMD have been evaluated in two large phase III, multicenter,
      randomized, double-masked, controlled pivotal trials in different neovascular AMD
      patient populations. Combined, the trial results indicate that ranibizumab
      results not only in a slowing down of vision loss but also in a significant
      proportion of patients experiencing a clinically meaningful vision gain. The
      visual acuity benefit over control was observed regardless of CNV lesion type.
      Furthermore, the benefit was associated with a low rate of serious adverse
      events. CONCLUSIONS: Ranibizumab represents a novel therapy that, for the first
      time, appears to have the potential to enable many AMD patients to obtain a
      meaningful and sustained gain of vision. On June 30 2006, ranibizumab was
      approved by the US Food and Drug Administration for the treatment of wet AMD.

PMID- 17031285
TI  - Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth
      factor in two patients.
AB  - BACKGROUND: Vitreous levels of unbound bevacizumab (Avastin) and unbound vascular
      endothelial growth factor (VEGF) were determined in two patients. Patient 1
      underwent repair of an 8-day-old rhegmatogenous retinal detachment 4 weeks after
      a single intravitreal bevacizumab injection, and Patient 2 underwent vitreous
      biopsy for endophthalmitis 48 hours after a combined bevacizumab and
      triamcinolone injection. METHODS: The samples of vitreous fluid were analyzed for
      unbound bevacizumab and unbound VEGF levels using microsphere immunoassays
      targeted for bevacizumab and VEGF. RESULTS: In Patient 1, the unbound bevacizumab
      level was 0.16% of the loading dose (or 500,000 pg/mL) and the unbound VEGF
      concentration was <41 pg/mL 4 weeks after the bevacizumab injection. In Patient
      2, the unbound bevacizumab level was 53% of the loading dose (or 166,000,000
      pg/mL) at 48 hours, with an unbound VEGF level of <41 pg/mL. CONCLUSION: A single
      dose of intravitreal bevacizumab is likely to provide complete intravitreal VEGF
      blockade for a minimum of 4 weeks, with an intravitreal bevacizumab half-life of
      approximately 3 days.

PMID- 17031286
TI  - Evaluation of anterior chamber inflammatory activity in eyes treated with
      intravitreal bevacizumab.
AB  - PURPOSE: To evaluate the effect of intravitreal bevacizumab on anterior chamber
      inflammatory activity. METHODS: Sixty-one consecutive patients with neovascular
      age-related macular degeneration were examined before, 1 day, and 1 week after
      intravitreal administration of 1 mg of bevacizumab (0.04 mL) for neovascular age
      related macular degeneration. The intravitreal injection was performed under
      sterile conditions. Twenty-one fellow eyes served as controls. The anterior
      chamber inflammatory activity was evaluated using biomicroscopy and the laser
      flare meter (Kowa FM-500, Kowa Company, Ltd., Tokyo, Japan). RESULTS: None of the
      61 consecutive patients had a significant, clinically detectable inflammatory
      response within 1 week of follow-up. Anterior chamber inflammatory activity
      measured by the laser flare meter ranged from 1.9 counts/ms to 70.0 counts/ms
      (mean +/- SD, 13.2 +/- 16.9 counts/ms; 95% confidence interval [CI], 7.8-18.6)
      before treatment. One day and 1 week after injection, values were between 3.2
      counts/ms and 30.0 counts/ms (mean +/- SD, 9.1 +/- 6.2 counts/ms; 95% CI, 7.2
      11.1) and 2.0 counts/ms and 25.1 counts/ms (mean +/- SD, 7.3 +/- 4.6 counts/ms;
      95% CI, 5.8-8.8), respectively. There was a significant reduction of anterior
      chamber flare at 1 week compared with baseline (P = 0.031). The control eyes had
      constantly low flare measures. CONCLUSION: No inflammatory response was detected
      clinically and by the laser flare meter after intravitreal bevacizumab
      administration. The slight reduction in anterior chamber flare could be due to
      the known antiinflammatory effect of anti-vascular endothelial growth factor
      therapy.

PMID- 17031287
TI  - Safety of intravitreal injection of bevacizumab in rabbit eyes.
AB  - PURPOSE: To evaluate the safety of intravitreal injection of bevacizumab in
      rabbits using electrophysiological testing and histopathologic analysis. METHODS:
      New Zealand albino rabbits were injected in one eye with control antibody (n =
      2), 0.05 mL of bevacizumab (n = 3), or 0.2 mL of bevacizumab (n = 3).
      Electroretinograms were obtained 1 week and 4 weeks after injection. Histologic
      analysis was performed after completion of the electroretinographic studies.
      RESULTS: No statistical differences were seen in scotopic and photopic a- and b
      wave amplitudes between untreated control and bevacizumab-injected eyes. No
      histopathologic differences were identified between untreated control and
      bevacizumab-injected eyes. CONCLUSION: Our study did not find evidence of retinal
      toxicity from a single intravitreal injection of bevacizumab in rabbits.

PMID- 17031288
TI  - One-year safety and efficacy of intravitreal triamcinolone acetonide for the
      management of macular edema secondary to central retinal vein occlusion.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone
      acetonide (IVTA) as treatment for macular edema associated with central retinal
      vein occlusion (CRVO). METHODS: A retrospective review was performed of data for
      40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA
      at the Bascom Palmer Eye Institute (Miami, FL). RESULTS: Median duration of
      symptoms before the first injection was 3 months (range, 1 day to 8 years).
      Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light
      perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P
      = 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P
      = 0.569; n = 17). Vision improved by > or =3 lines in 21% of eyes at 1 month, 27%
      at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from
      baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received
      more than one injection (mean = 1.6 injections; range 1-4 injections). Overall,
      intraocular pressure increased by > or =10 mmHg in 24% of eyes at 1 year.
      Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle
      glaucoma. CONCLUSION: IVTA can substantially improve vision in some patients, but
      most patients have stable visual acuity compared with baseline at 1 year despite
      repeated injections.

PMID- 17031289
TI  - Intravitreal triamcinolone acetonide treatment of macular edema associated with
      central retinal vein occlusion.
AB  - PURPOSE: To evaluate treatment of macular edema associated with central retinal
      vein occlusion (CRVO) using intravitreal triamcinolone acetonide. METHODS:
      Retrospective review of data for 29 eyes of 29 patients with CRVO and macular
      edema treated with intravitreal triamcinolone acetonide. Initial visual acuity,
      intraocular pressure, and history of glaucoma were recorded. Final visual acuity,
      intraocular pressure, and adverse events were recorded during the treatment
      period. RESULTS: Twenty-nine eyes were treated with intravitreal injection. The
      mean follow-up was 348 days. The median initial Early Treatment Diabetic
      Retinopathy Study visual acuity was 20/250 (median logMAR, 1.1). The median
      visual acuity 3 months after injection was 20/125 (median logMAR, 0.8). This
      difference was statistically significant. The median final visual acuity was
      20/250 (median logMAR, 1.1). This difference in visual acuity was not
      statistically significant. Elevated intraocular pressure, excluding that related
      to neovascularization, occurred in 5 of 22 patients. Subgroup analysis revealed
      that patients who received multiple injections had better outcomes. CONCLUSION:
      Intravitreal triamcinolone acetonide may improve vision transiently but does not
      appear to result in a sustained visual acuity benefit for patients with macular
      edema associated with CRVO. Repeated injections may be necessary. The risk of
      glaucoma is significant, and additional study is required to further characterize
      this and other risks.

PMID- 17031290
TI  - Outcomes of macular hole surgery and shortened face down positioning.
AB  - PURPOSE: Internal limiting membrane (ILM) peeling in macular hole surgery may
      allow a shortened period of face down positioning. This study reports the results
      of macular hole surgery combined with shortened (3-day) face down positioning.
      METHODS: The study was a retrospective review of data for 21 patients (21 eyes)
      treated for a macular hole by a single surgeon (G.K.S.). All patients underwent
      standard 3-port pars plana vitrectomy with triamcinolone-assisted ILM peeling and
      gas tamponade with 16% C3F8 or 25% SF6. Patients were instructed to remain in a
      face down position for 3 days at least 8 hours a day and to avoid flat on back
      positioning. RESULTS: The main outcome of anatomical closure was achieved in 20
      (95%) of 21 eyes. Snellen visual acuity improved >2 lines in 76% (16/21) of
      patients. No patient lost >1 line of Snellen visual acuity. Two patients had
      postoperative increased (>24 mmHg) intraocular pressure that was successfully
      treated with pressure-lowering drops. Initial surgery failed to achieve hole
      closure in one patient, but with a second surgery and similar face down
      positioning, the hole was closed. CONCLUSIONS: This study found that macular hole
      surgery with ILM peeling and a shortened period of face down positioning achieves
      excellent anatomical closure and is not associated with significant adverse
      outcomes.

PMID- 17031291
TI  - Successful treatment of persistent macular holes using "heavy silicone oil" as
      intraocular tamponade.
AB  - BACKGROUND: Silicone oil tamponade has been suggested in the treatment of
      persistent macular hole, but visual outcome is often poor. We describe two
      patients who underwent reoperation for persistent macular hole using "heavy
      silicone oil" (HSO) tamponade. METHODS: Two patients who underwent vitrectomy,
      removal of the posterior vitreous cortex, peeling of the internal limiting
      membrane, and long-acting gas tamponade had persistent macular hole 3 months
      after surgery. The patients underwent reoperation using an HSO (Oxane Hd, Bausch
      & Lomb) as internal tamponade. This tamponade did not require postoperative
      posturing and was removed after 3 months. Optical coherence tomography (OCT) was
      performed, and visual outcome was determined. RESULTS: OCT images showed that the
      HSO bubble conformed well with the retinal surface in the foveal region. Closure
      of the macular hole was achieved in both patients. Visual acuity increased from
      20/100 to 20/40 in Patient 1 and from 20/600 to 20/100 in Patient 2. CONCLUSION:
      HSO can be a useful tool in the treatment of persistent macular hole. OCT images
      showed that the tamponade was effective in the upright position in the foveal
      region. OCT allowed determination of the time of tamponade removal according to
      the anatomical stage of hole closure.

PMID- 17031292
TI  - Combined pars plana phacofragmentation, vitrectomy, and Artisan lens implantation
      for traumatic subluxated cataracts.
AB  - PURPOSE: To report on the outcome of combined pars plana phacofragmentation,
      vitrectomy, and Artisan lens implantation in the management of subluxated
      cataracts. METHODS: This prospective, interventional, nonrandomized case series
      included nine eyes of seven consecutive adult patients with traumatic lens
      subluxation. Pre- and postoperative data (complete manifest refraction, best
      spectacle-corrected visual acuity, slit-lamp examination findings, intraocular
      pressure, fundus status, numerical density of endothelial cells, corneal
      thickness, and complications) were collected prospectively for all patients.
      RESULTS: After a median postoperative follow-up of 12 months (range, 8-18
      months), a mean spherical equivalent of -0.50 +/- 0.87 diopter (range, +1 to 
      1.50 diopter) was achieved. The mean logarithm of the minimum angle of resolution
      visual acuity improved from 1 (preoperatively) to 0.1 (postoperatively) (P =
      0.007, Wilcoxon test). Median endothelial cell losses of 15 +/- 8% (P = 0.008)
      and 14 +/- 16% (P = 0.011) were registered at follow-ups of 1 month and 12
      months, respectively. Postoperative complications included chronic intraocular
      inflammation and superior corectopia. CONCLUSIONS: Our procedure appears to be a
      safe, accurate, stable, and efficacious option for the management of traumatic
      subluxated cataracts in adults. However, longer-term data are needed to evaluate
      the corneal endothelium.

PMID- 17031293
TI  - Correlation of optical coherence tomography pattern and visual recovery after
      vitrectomy with silicone oil for retinal detachment.
AB  - PURPOSE: To assess prospectively the features of the macular surface in silicone
      oil-filled eyes after surgery by analyzing whether silicone oil affects optical
      coherence tomography (OCT) measurements and their reproducibility and whether a
      statistical correlation exists between postoperative best-corrected visual acuity
      (BCVA) and foveal thickness measured by OCT. METHODS: Twenty eyes of 20 patients
      underwent vitrectomy with silicone oil tamponade for retinal detachment. After
      vitrectomy, complete ophthalmic examination including determination of BCVA and
      OCT was performed to quantify the visual recovery and the foveal thickness.
      RESULTS: Ophthalmoscopy revealed that the retina appeared to be reattached in all
      20 eyes at 3 months after surgery. BCVA ranged from 0.4 logMAR to 1.7 logMAR, and
      foveal thickness ranged from 80 microm to 500 microm. Postoperative foveal
      thickness and BCVA had a strong correlation (r = 0.93; P = 0.003). CONCLUSION:
      The presence of silicone oil in the vitreous chamber does not change the
      reproducibility of OCT measurements of foveal thickness (coefficient of
      reproducibility, 1.48%). This study showed high statistical correlation between
      BCVA and foveal thickness. Therefore, postoperative BCVA is affected by
      postoperative foveal thickness, and visual improvement is limited in eyes with
      increased or decreased foveal thickness.

PMID- 17031294
TI  - Optical coherence tomography in the diagnosis and monitoring of cystoid macular
      edema in patients with retinitis pigmentosa.
AB  - PURPOSE: To identify cystoid macular edema (CME) in patients with retinitis
      pigmentosa (RP) using optical coherence tomography (OCT) and to evaluate response
      to acetazolamide by serial OCT. METHODS: Twenty-nine consecutive RP patients were
      included in the study. Patients with CME were treated with acetazolamide (125 or
      250 mg/d for 4-12 months). OCT, fluorescein angiography, and determination of
      best-corrected visual acuity (BCVA) were performed initially and throughout the
      follow-up period. RESULTS: Ten of the 29 patients had CME by OCT. Of these 10
      patients, 5 had various degrees of fluorescein leakage by fluorescein
      angiography. After acetazolamide treatment, six patients had significant
      decreases in macular edema in at least one eye by follow-up OCT. In six patients,
      visual acuity improved by > or =1 line in at least one eye. The change of central
      foveal thickness shown by OCT was significantly correlated with the change of
      logMAR of BCVA (Pearson correlation coefficient [r] = 0.576; P = 0.008). We
      observed no differences in the change of central foveal thickness by OCT (Mann
      Whitney test; P = 1.000) and in the change of logMAR of BCVA (Mann-Whitney test;
      P = 0.106) between patients treated with 125 mg/d acetazolamide and those treated
      with 250 mg/d acetazolamide. CONCLUSIONS: These results indicate that OCT is a
      valuable tool in the detection and follow-up of CME in RP patients. Treatment
      with acetazolamide resulted in marked improvement in OCT-diagnosed CME in RP, but
      visual improvement was variable.

PMID- 17031295
TI  - Assessment of retinal function in patients with HIV without infectious retinitis
      by multifocal electroretinogram and automated perimetry.
AB  - PURPOSE: To determine if multifocal electroretinogram (mfERG) testing shows
      abnormalities that correspond to perimetric defects in HIV positive patients
      without infectious retinitis. METHODS: We studied three groups of patients: HIV
      negative controls, HIV high CD4 nadir patients (lowest CD4 T cell count is over
      100) and low CD4 nadir patients (below 100 for over 6 months). Twenty-six HIV
      positive eyes and 16 HIV negative control eyes were studied by mfERG. A subset of
      10 eyes also underwent computerized perimetry for comparison. We analyzed mfERG
      by hexagons as well as by quadrants and rings. RESULTS: Of 103 hexagon locations
      there was no significant difference in the amplitudes P1 and N1 (nV/degree)
      between the three studied groups (p>0.05), similarly, the latencies were not
      different (p>0.05). All eyes with significant visual field defects at the 0.01
      and 0.005 level (Humphrey pattern deviation; 24-2) were compared to mfERG
      amplitudes and latencies at those locations-there were no corresponding defects
      in mfERG data (p>0.2). CONCLUSION: In the era of HAART there are still
      demonstrable visual field defects and other evidence of damage to the retinal
      nerve fiber layer in HIV patients. Our mfERG studies show that the damage appears
      to affect the inner retina, the outer retina is spared. Further studies of inner
      retinal structure and function are indicated to elucidate this process.

PMID- 17031296
TI  - Intravitreal voriconazole for drug-resistant fungal endophthalmitis: case series.
AB  - PURPOSE: To report the efficacy of intravitreal voriconazole. METHODS:
      Retrospective analysis of an interventional case series of five cases of culture
      proven fungal endophthalmitis treated with intravitreal voriconazole was done.
      Only cases found to be resistant to conventional antifungal agents were included
      in the study. The diagnosis of fungal endophthalmitis was established on the
      basis of clinical as well as microbiological examination. All patients received
      one or more intravitreal injections of voriconazole. Resolution was determined on
      the basis of clinical examination. Resolution of infection and final visual
      acuity were the main outcome measures. RESULTS: Resolution of infection was
      achieved in all five cases. Visual acuity was better in three cases and was
      maintained in two. Of the three patients who had improvement, two had vision
      better than or equal to 20/120. Evisceration was avoided in one case with maximal
      antifungal treatment including voriconazole. CONCLUSIONS: Voriconazole definitely
      adds to the available treatment options for fungal endophthalmitis. Because of
      its broad spectrum of activity, it is efficacious in even amphotericin-B- and
      fluconazole-resistant fungal endophthalmitis.

PMID- 17031297
TI  - X-linked retinoschisis: novel mutation in the initiation codon of the XLRS1 gene
      in a large family.
AB  - PURPOSE: To describe a novel point mutation in the initiation codon of the XLRS1
      gene in a large family and the clinical features of males affected with X-linked
      juvenile retino-schisis. METHODS: Genealogic investigation and mutation screening
      of the XLRS1 gene were performed for a 4-generation family consisting of 72
      members. Affected males were evaluated clinically between 1986 and 2004 with up
      to 18 years of follow-up. RESULTS: We identified a novel point mutation (1A>T
      transversion) in the initiation codon of the XLRS1 gene in affected males
      resulting in an amino acid substitution of methionine to leucine (Met1Leu),
      therefore abolishing the translation initiation Met codon. CONCLUSION:
      Identification of the disease-causing mutation in this family with long-term
      follow-up allows for earlier and more accurate identification of individuals at
      risk for this inherited progressive macular degeneration, provides for more
      accurate genetic counseling, and contributes to our understanding of the
      pathophysiology of this disorder.

PMID- 17031298
TI  - A novel complex mutation event in the peripherin/RDS gene in a family with
      retinal pattern dystrophy.
AB  - PURPOSE: To report a complex mutation in the peripherin/RDS gene found in a
      family in whom retinal pattern dystrophy is segregating as an autosomal dominant
      trait. METHODS: Clinical data were collected from family members of a large Swiss
      family affected by autosomal dominant retinal pattern dystrophy. Single strand
      conformation polymorphism (SSCP) analysis of the candidate gene peripherin/RDS
      and subsequent sequencing of the first exon were performed. RESULTS: Pattern
      dystrophy of the retina was suspected in 18 family members aged 30 years or
      older. Assuming a homogeneous phenotype, the candidate locus peripherin/RDS was
      investigated. SSCP analysis of the first exon of the peripherin/RDS gene showed
      an aberrant pattern in 18 affected individuals. Direct sequencing of polymerase
      chain reaction products detected a complex mutation, del265-268GCCA ins AGGGCC,
      leading to a stop codon at amino acid position 99. CONCLUSION: To our knowledge,
      we report the first complex mutation in the peripherin/RDS gene as the cause of a
      mild macular phenotype, supporting the importance of molecular diagnosis in
      genetic counseling.

PMID- 17031299
TI  - Diagnostic and therapeutic challenges.

PMID- 17031300
TI  - Treatment of choroidal neovascularization in pathologic myopia with intravitreal
      bevacizumab.

PMID- 17031301
TI  - Standing vitrectomy in morbid obesity.

PMID- 17031302
TI  - Adhesion of heavy oil to posterior lens capsule.

PMID- 17031303
TI  - Biomechanical significance of the human internal limiting lamina.

PMID- 17031304
TI  - Application of YAG laser retinopuncture for perfluorocarbon liquid removal from
      under retina after vitreoretinal surgery.

PMID- 17031305
TI  - Ophthalmomyiasis associated with Fuchs heterochromic iridocyclitis.

PMID- 17031306
TI  - Transpupillary thermotherapy for large-sized subfoveal circumscribed choroidal
      hemangioma.

PMID- 17031307
TI  - Aicardi syndrome: chorioretinal lacunae without corpus callosum agenesis.

PMID- 17031309
TI  - Comment on incidence of rhegmatogenous retinal detachment after vitrectomy in
      eyes of diabetic patients.

PMID- 17031310
TI  - 2006 Otto Aufranc Award Paper: significance of in vivo degradation for
      polyethylene in total hip arthroplasty.
AB  - Our research group developed an implant retrieval program to study in vivo
      degradation of polyethylene. We now have evidence to support our hypothesis that
      degradation of radiation-sterilized polyethylene occurs in the body for not only
      historical gamma air sterilized liners, but also for conventional gamma inert
      sterilized (ArCom) and annealed highly crosslinked polyethylene (Crossfire)
      liners as well. Our research has also led to the discovery that the most severe
      manifestations of in vivo oxidation typically occur in regions of the liner
      experiencing minimal wear, such as the rim of the component, where the body
      fluids (containing oxidizing species) have access to the polyethylene. Our data
      from historical, ArCom, and Crossfire retrievals all point to a similar scenario
      in which the femoral head limits the in vivo oxidation of polyethylene at the
      bearing surface. Consequently, provided rim impingement does not occur, and the
      polyethylene locking mechanisms remain relatively isolated from oxidizing fluid,
      in vivo oxidation does not seem to be clinically important in the first 10 years
      of implantation for conventional gamma sterilized polyethylene. We conclude that
      in vivo degradation should be included among the list of potential long-term
      failure modes for modular polyethylene components for total hip arthroplasty.

PMID- 17031311
TI  - An integrated solution to acetabular revision surgery.
AB  - The three salient reasons for failure of acetabular revision surgery have been
      failure of fixation, wear and lysis, and dislocation. This review focuses on the
      major progress made in addressing these three items, leading to an overall
      approach integrating three contemporary techniques with a strong likelihood of
      improving acetabular revision surgery. These three techniques are the use of
      hemispheric cementless acetabular components, alternate bearings, and big heads.

PMID- 17031312
TI  - Multimodal analgesia without routine parenteral narcotics for total hip
      arthroplasty.
AB  - Methods for managing pain after a total hip replacement have changed
      substantially in the past 5 years. We documented the outcome of patients treated
      with a multimodal pain program designed to avoid parenteral narcotics. Avoidance
      of parenteral narcotics can essentially eliminate the complications of
      respiratory depression, ileus, and narcotic-induced hypotension. It can minimize
      nausea and vomiting which cause dissatisfaction with an operation. Twenty-one of
      140 patients (15%) needed parenteral narcotics postoperatively with only nine
      patients (6.4%) using parenteral narcotics after the day of surgery. Mean pain
      scores were below 3 of 10 on all postoperative days. There were no patients with
      respiratory depression or ileus, and four (2.9%) with urinary retention. Nausea
      occurred with 35 patients (25%) in the recovery room and in 28 patients (20%)
      thereafter. Emesis occurred in five patients (3.6%) with two incidences in the
      recovery room. One hundred and thirty-eight patients (98.6%) were discharged home
      at a mean of 2.7 seven days postoperatively with 98 (70%) on a single assistive
      device. The multimodal pain management program, which avoided parenteral
      narcotics, was effective in providing pain relief, nearly eliminating emesis, and
      eliminating the severe complications of respiratory depression, urinary tract
      infection and ileus, as well as accelerating function.

PMID- 17031313
TI  - Femoral supracondylar malunions with varus medial condyle and shortening.
AB  - Femoral supracondylar malunions associated with varus deformity of the medial
      femoral condyle and shortening are rare, and all techniques for treatment of this
      complication reported to date have limitations. A one-stage antegrade locked
      intramedullary nailing technique to concomitantly treat these combined disorders
      was performed in 19 consecutive patients. The following procedures were
      performed: removal of previous implants, supracondylar corrective osteotomy, one
      stage lengthening on a fracture table, antegrade static locked intramedullary
      nail stabilization, and corticocancellous bone grafting. Seventeen patients with
      malunions received regular followup for a median of 2.4 years (range, 1.1-5.2
      years). Sixteen malunions healed with a union rate of 94.1% (16 patients) and a
      median union period of 4.5 months (range, 3-7 months). Only one nonunion
      associated with nail breakage occurred (5.9%; one patient) and one deep infection
      recurred (5.9%; one patient). Both patients recovered after appropriate
      treatment. All patients had improved knee alignment and function. Antegrade
      locked intramedullary nailing is an effective technique for one-stage treatment
      of combined disorders in patients with femoral supracondylar malunions.
      Complications can be avoided if patients and surgeons are careful during the
      treatment course. Protected weightbearing until fracture healing is crucial to
      successful treatment.

PMID- 17031314
TI  - Two- to 9-year clinical results of alumina ceramic-on-ceramic THA.
AB  - From June 1997 to June 2003 we performed 194 total hip arthroplasties on 173
      patients using alumina ceramic-on-ceramic bearings as part of a prospective
      United States Food and Drug Administration/Investigational Device Exemption
      study. The average patient age at surgery was 49.9 years. Minimum followup time
      was 2 years (mean 4.3 years, range 2-9 years). We evaluated survival rate,
      implant- and nonimplant-related complications. Clinical outcomes included the
      Merle d'Aubigne score. We assessed radiographs for signs of osteolysis, component
      loosening, and implant wear. No patients had osteolysis and there were no hip
      dislocations. Implant survivorship for all hips with aseptic revision of any
      component was 96% (CI, 91-100) at 9 year; survivorship for hips without prior
      surgery was 99.3%, (CI, 98-100). There was a 1.7% incidence of implant-related
      complications. Our data help confirm two United States FDA/IDE studies on alumina
      ceramic-on-ceramic total hip arthroplasty that reported low aseptic revision
      rates and low revision rates for instability. Total hip arthroplasty using
      alumina ceramic-on-ceramic implants is a safe and reliable procedure in the
      comparably young and active patient.

PMID- 17031315
TI  - Rating of internal fixation and clinical outcome in displaced femoral neck
      fractures: a prospective multicenter study.
AB  - The influence of precise surgical technique on the clinical outcome of internal
      fixation for displaced femoral neck fractures is an under-reported and potential
      confounding factor in randomized studies involving internal fixation as a
      treatment modality. Two experienced surgeons blindly rated internal fixation
      techniques on the perioperative radiographs of 102 patients selected for internal
      fixation in a prospective multicenter 2-year followup study. Overall technical,
      fracture reduction, and implant positioning ratings were given according to
      instruction. One or both raters assigned an inadequate overall rating in 25% of
      patients. There was a correlation with 2-year clinical internal fixation failure
      for overall technique and fracture reduction rating. Implant positioning did not
      correlate with 2-year internal fixation failure. Correlation increased if both
      raters agreed on inadequate technique. One inadequate rating indicated a problem
      could arise, whereas two inadequate ratings strengthened this problem likelihood.
      Adjudication of technique by independent rater(s) is useful, may have clinical
      implications, and should be performed routinely in future studies involving
      internal fixation in patients with displaced femoral neck fractures.

PMID- 17031316
TI  - Viral load and CD4 count dynamics after HIV-1 seroconversion in homosexual and
      bisexual men in Rio de Janeiro, Brazil.
AB  - PURPOSE: Reliable predictors of HIV disease progression are scarce in developing
      countries, where most HIV infections occur. We describe early virologic and
      immunologic events among men who have sex with men in Rio de Janeiro, Brazil.
      METHODS: Seroconverters from 2 high-risk cohorts were followed for up to 36
      months with periodic laboratory evaluations, plasma viral load, and CD4 count
      assessments. Viral load and CD4 count mean trajectories were computed. For the
      modeled viral loads, mean and median values were 24,480 (4.36 log10) and 19,720
      (4.29 log10) copies/mL (range 14,880-58,090), respectively. Median CD4 count was
      373 cells/microL (range 260-508). Overall variation on viral loads ranged from
      4.3 to 5.2 log10 copies/mL with a visible increase in the viral load starting at
      approximately 600 days (n = 12) after estimated time of seroconversion. The
      initial period of HIV infection was characterized by an increase in CD4 count (n
      = 29) followed by a steep decline starting at approximately 200 days (508 cells,
      95% CI: 425 to 569). A gradual decrease was observed in the median CD4 count
      thereafter, reaching 281 (95% CI: 100 to 466) at 1000 days after the estimated
      date of seroconversion. CONCLUSIONS: Although viral load dynamics resembled those
      observed in developed countries, CD4 counts seem to decline at a faster rate than
      in the Multicenter AIDS Cohort Study (MACS) cohort. Clinical and survival data
      are needed to assess the impact of interventions, such as antiretroviral therapy,
      on the clinical course of HIV infection in Brazil.

PMID- 17031317
TI  - Acceptability of formula-feeding to prevent HIV postnatal transmission, Abidjan,
      Cote d'Ivoire: ANRS 1201/1202 Ditrame Plus Study.
AB  - OBJECTIVE: To describe the maternal acceptability of formula-feeding proposed to
      reduce postnatal HIV transmission in Abidjan, Cote d'Ivoire. METHODS: Each
      consenting HIV-infected pregnant women, age > or =18 years, who received a
      perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant
      feeding options were proposed antenatally: exclusive formula-feeding or short
      term exclusive breast-feeding. Formula-feeding was provided free up to age 9
      months. Determinants of acceptability were analyzed using a logistic regression.
      Formula-feeding failure was defined as having breast-fed one's child at least
      once. RESULTS: Between March 2001 and March 2003, 580 women delivered: 97%
      expressed their infant-feeding choice before delivery; 53% chose formula-feeding.
      Significant prenatal determinants for refusing formula-feeding were: living with
      her partner, being Muslim, having a low educational level, being followed in one
      of the study sites, having not disclosed her HIV status, and having been included
      within the first 6 months of the project. Among the 295 mothers who formula-fed,
      the Kaplan-Meier probability of success of the formula-feeding option was 93.6%
      at Day 2 (95% confidence interval [CI]: 90.7% to 96.3%) and 84.2% at 12 months
      (95% CI: 79.9% to 88.5%): 46 of 295 (15.6%) women breast-fed at least once, of
      whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or
      newborn poor health. CONCLUSIONS: In settings with general access to clean water,
      structured antenatal counseling, and sustained provision of free formula,
      slightly over half of HIV-infected women chose to artificially feed their newborn
      infant. Low mixed-feeding rates were observed. This social acceptability must be
      balanced with mother-child long-term health outcomes to guide safe
      recommendations on infant-feeding among HIV-infected women in African urban
      settings.

PMID- 17031318
TI  - Late diagnosis of HIV infection: trends, prevalence, and characteristics of
      persons whose HIV diagnosis occurred within 12 months of developing AIDS.
AB  - BACKGROUND: Persons diagnosed late in the course of HIV infection may be
      unknowingly transmitting infection and once diagnosed may have worse outcomes and
      greater medical expenses. METHODS: Persons diagnosed with AIDS in San Francisco
      between 2001 and 2005 were included. Late testers were persons diagnosed with HIV
      12 months or less before their AIDS diagnosis. Prevalence trends, demographic and
      risk correlates, and predictors of late testing were measured. RESULTS: Among
      2139 persons included, 830 (38.8%) were late testers. The prevalence of late
      testing was stable between 2001 and 2005. Late testing was more likely among
      persons <30 years old (Odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.4,
      2.8), heterosexuals (OR: 1.88, 95% CI: 1.1, 3.1), persons without a reported risk
      (OR: 2.88, 95% CI: 1.7, 5.0), persons with private insurance (OR: 1.82, 95% CI:
      1.4, 2.4), no insurance (OR: 1.83, 95% CI: 1.4, 2.4), born outside of the United
      States (OR: 1.64, 95% CI: 1.2, 2.2), and whose initial AIDS diagnosis was an
      opportunistic infection (OR: 2.24, 95% CI: 1.8, 2.8). CONCLUSIONS: A large
      proportion of persons with AIDS have tested late in the course of HIV infection
      and this proportion has not declined in recent years. Routine testing in medical
      settings, and use of rapid oral-fluid testing in traditional and nontraditional
      settings may increase early HIV diagnosis.

PMID- 17031319
TI  - Home-based antiretroviral care is associated with positive social outcomes in a
      prospective cohort in Uganda.
AB  - BACKGROUND: Home-based antiretroviral therapy (ART) care in Africa has expanded;
      but social outcomes of home-based ART programs are unknown. METHODS: Social
      experiences of participants in an antiretroviral therapy program involving weekly
      home visits in Uganda were assessed through interviews at enrollment and after 3
      months and analyzed using generalized estimating equations. RESULTS: Of 654
      participants, 72% were women; median baseline CD4 cell-count was 123 cells/muL.
      At follow-up, participants were more likely to report community support (adjusted
      odds ratio [OR] 2.10, 95% confidence interval [CI]: 1.46 to 3.03, P < 0.001),
      family support (OR 2.65, CI: 2.01 to 3.49, P < 0.001), and relationship
      strengthening (OR 2.10, CI: 1.46 to 3.03, P = 0.001) than at baseline; 84%
      attributed these experiences to antiretroviral therapy program participation.
      There was no change in incidence of negative experiences (P = 0.3). Forty-six
      percent of women reported a history of partner abuse, but abuse rates 3 months
      before and after program initiation were low (1% vs. 2%, OR 3.20, CI: 0.94 to
      10.9, P = 0.063). Of five women who reported abuse associated with program
      participation, all had history of domestic violence. Of all participants
      reporting outcomes associated with antiretroviral therapy program participation
      at follow-up, 464 (79%) had only positive experiences, 35 (6%) had both positive
      and negative experiences, and <1% had only negative experiences. CONCLUSIONS:
      Participation in a home-based antiretroviral therapy program was associated with
      multiple positive social outcomes.

PMID- 17031320
TI  - Identification of a novel circulating recombinant form (CRF33_01B) disseminating
      widely among various risk populations in Kuala Lumpur, Malaysia.
AB  - A molecular epidemiological investigation was conducted among various risk
      populations (n = 184) in Kuala Lumpur, Malaysia, in 2003 to 2005, on the basis of
      nucleotide sequences of protease and reverse transcriptase regions. In addition
      to circulating HIV-1 strains, including CRF01_AE (57.1%), subtype B (20.1%), and
      subtype C (0.5%), we detected a candidate with a new circulating recombinant form
      (CRF). We determined four near-full-length nucleotide sequences with identical
      subtype structure from epidemiologically unlinked individuals of different risk
      and ethnic groups. In this chimera, two short subtype B segments were inserted
      into the gag-RT region in a backbone of CRF01_AE. The recombinant structure was
      distinct from previously identified CRF15_01B in Thailand. In agreement with the
      current HIV nomenclature system, this constitutes a novel CRF (CRF33_01B). The
      overall prevalence of CRF33_01B is 19.0% (35/184). Although the prevalence of
      CRF33_01B is particularly high among injecting drug users (42.0%, 21/50), it is
      also detected in a substantial proportion of homo-/bisexual males (18.8%, 3/16)
      and heterosexuals (9.8%, 9/92). Moreover, unique recombinant forms composed of
      CRF01_AE and subtype B that have a significant structural relationship with
      CRF33_01B were detected in 1.6% (3/184) of study subjects, suggesting an ongoing
      recombination process in Malaysia. This new CRF seems to be bridging viral
      transmission between different risk populations in this country.

PMID- 17031321
TI  - Integration of antiretroviral treatment within antenatal care in Gauteng
      Province, South Africa.
AB  - BACKGROUND: Antenatal clinics are a key entry point into HIV treatment and care,
      together with interventions to reduce mother-to-child transmission (MTCT).
      Further evaluation is needed of interventions linking antenatal with
      antiretroviral (ARV) treatment services and effectiveness of triple-ARV regimens
      for reducing MTCT in resource-constrained settings. METHODS: Data were gathered
      from HIV-infected women attending antenatal care from June 2004 to July 2005 at
      Coronation Women and Children Hospital, South Africa. After a patient record
      review, interventions were implemented to strengthen service linkages and
      integrate ARV treatment within antenatal care. Laboratory investigations were
      streamlined, including CD4 cell count testing at the first antenatal visit. MTCT
      risk for women initiating ARV treatment is compared with that of women-infant
      pairs receiving single-dose nevirapine (sd-NVP). RESULTS: In total, 164 pregnant
      women initiated ARV treatment and 863 received sd-NVP. After changes to service
      delivery, time-to-treatment initiation was reduced from a median of 56 days to 37
      days (P = 0.041). The risk of MTCT for women receiving ARV treatment (5 [4.3%] of
      116 women) was lower than for those given sd-NVP (74 [10.7%] of 692 women; P =
      0.032). CONCLUSIONS: Strengthening linkages and integrating key components of ARV
      treatment within antenatal care reduces time-to-treatment initiation. In this
      setting, among women with a high MTCT risk, triple-ARV regimens are effective in
      reducing HIV infection in infants.

PMID- 17031322
TI  - A new implantable middle ear hearing device for mixed hearing loss: A feasibility
      study in human temporal bones.
AB  - HYPOTHESIS: To assess the feasibility of a new, active middle ear device in
      temporal bones (TB). BACKGROUND: This device is designed for patients with mixed
      hearing loss subsequent to chronic middle ear infection, surgery, or trauma. This
      Bell-Vibroplasty is built from a VIBRANT MED-EL Vibrant Soundbridge and a Kurz
      Bell titanium partial ossicular replacement prosthesis. METHODS: In three fresh
      TBs, healthy and reconstructed middle ears were analyzed by means of laser
      Doppler interferometry. The sound transmission properties of a partial ossicular
      replacement prosthesis and a passive and an active Bell-Vibroplasty were compared
      with healthy middle ear function. RESULTS: The measurements provided reliable
      results with small standard deviations and good signal-to-noise ratios. The
      performance levels of the partial ossicular replacement prosthesis and of the
      passive Bell-Vibroplasty were comparable with that of healthy middle ear
      function. The activated Bell-Vibroplasty provided linear function and a flat
      frequency response within the measured frequency range (500 Hz-8 kHz), with peak
      deviations of less than 10 dB. The maximum output of the Bell-Vibroplasty was
      equivalent to 125-dB sound pressure level. CONCLUSION: Bell-Vibroplasty is
      feasible in TBs. Bell-Vibroplasty performance in TBs is sufficient to allow for a
      clinical trial as a next step.

PMID- 17031323
TI  - The radiographic prevalence of geniculate ganglion dehiscence in normal and
      congenitally thin temporal bones.
AB  - OBJECTIVE: To determine the prevalence of a dehiscent geniculate ganglion on
      routine temporal bone computed tomography (CT). STUDY DESIGN: Retrospective case
      review. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy-eight
      consecutive temporal bone CT examinations for a total of 556 sides were reviewed.
      One hundred ninety-one sides were excluded. Reasons for exclusion included
      reconstructed coronal views, no coronal views, or a pathologic process, which
      involved the geniculate ganglion. Six examinations were from patients with
      clinical superior canal dehiscence confirmed by surgical repair or positive
      vestibular evoked myogenic potentials. Twenty-four scans were from patients with
      radiographic superior canal dehiscence confirmed by two independent readings.
      MAIN OUTCOME MEASURES: The incidence of geniculate ganglion dehiscence in
      patients with and without radiographic or clinical superior canal dehiscence.
      Dehiscent geniculate ganglion was defined as at least two consecutive cuts on a
      coronal CT showing no bone overlying the geniculate ganglion. RESULTS: The
      overall incidence of a dehiscent geniculate ganglion was 14.5% in the 365 sides
      reviewed. The incidence of a dehiscent geniculate ganglion is increased in
      patients with radiographic and clinical superior canal dehiscence as compared
      with normal patients and was significantly different by chi analysis (38.1 versus
      11.4%). CONCLUSION: The presence of radiographic geniculate ganglion dehiscence
      is common. This finding has particular importance when the middle cranial fossa
      or subtemporal approach is used, as the facial nerve is more at risk especially
      when used to address superior canal dehiscence.

PMID- 17031324
TI  - Infective causes of facial nerve paralysis.
AB  - OBJECTIVE: To review the functional recovery in a cohort of patients with facial
      nerve paralysis (FNP) due to infective cause. STUDY DESIGN: Retrospective review
      based on patients identified from a prospectively maintained database of patients
      with FNP. The case notes of identified patients were reviewed. SETTING: Tertiary
      referral center. PATIENTS: The patients were identified from a database of 1074
      patients with FNP. One hundred twenty of the 150 patients identified as having
      FNP due to an infectious disease caused by herpes zoster oticus were excluded
      from the study. The remaining 30 patients were included in the study.
      INTERVENTIONS: Patients were treated both operatively and nonoperatively.
      Operative treatment included myringotomy and ventilation tube placement, cortical
      mastoidectomy, modified radical (canal wall down) mastoidectomy, petrous
      apicectomy, and lateral temporal bone resection. MAIN OUTCOME MEASURES: This
      study used the House-Brackmann (HB) grade of facial function at 1 year after
      initial assessment. The patients were identified from a prospectively maintained
      database of all patients presenting with FNP to a single specialist
      otolaryngologist (G.R.C.) between June 1988 and April 2005. The database contains
      information including demographic details, dates of presentation, diagnostic
      modalities used, diagnosis, interventions, and HB grade. The patients in this
      series presented between August 4, 1989 and August 26, 2003. RESULTS: Twenty-nine
      patients with 30 facial nerve paralyses were identified. The causes of FNP were
      acute otitis media (n = 10); cholesteatoma (n = 10 [acquired, 7; congenital, 3]);
      mastoid cavity infections (n = 2); malignant otitis externa (n = 2);
      noncholesteatomatous chronic suppurative otitis media (CSOM; n = 2); tuberculous
      mastoiditis (n = 1); suppurative parotitis (n = 1); and chronic granulomatosis (n
      = 1). The patients with noncholesteatomatous CSOM who presented sooner after the
      onset of facial nerve symptoms had greater facial nerve recovery when assessed
      using the HB grade at 1 year. CONCLUSION: FNP due to infective causes other than
      herpes zoster oticus is rare. Patients with noncholesteatomatous CSOM and FNP
      have a better outcome than those with FNP due to cholesteatoma. Patients with FNP
      due to acute otitis media tend to have a good prognosis without surgical
      decompression of the facial nerve being required.

PMID- 17031325
TI  - Effects of a nitric oxide synthase Type II inhibitor on compound action potential
      thresholds in experimental endolymphatic hydrops.
AB  - HYPOTHESIS: Nitric oxide (NO) is likely to be synthesized by nitric oxide
      synthase Type II (NOS II) action and may partake in the origin of changes of
      compound action potential (CAP) threshold observed in guinea pigs with induced
      endolymphatic hydrops. This study aimed to assess the action of a NOS II
      inhibitor on CAP thresholds in these experimental samples. BACKGROUND: In guinea
      pigs with experimental endolymphatic hydrops, there are lesions on the cochlea
      and progressive increase of CAP threshold. NOS II was found in the cochlea of
      this animal model, and it was inferred that NO can contribute by such
      alterations. METHODS: The animals were divided into two groups, in which eight
      received an intake of a NOS II inhibitor, aminoguanidine, and another eight
      served as a control group. During 16 weeks, CAP thresholds at 1,000, 2,000, 4,000
      and 6,000 on electrocochleography were compared between the groups. RESULTS: The
      group that had an intake of aminoguanidine showed a lower increase on CAP
      thresholds at 2,000 (p < 0.05) and 6,000 Hz (p < 0.05) at the 12th postoperative
      week, and at 1,000 (p < 0.05), 2,000 (p < 0.001), 4,000 (p < 0.001), > and 6,000
      Hz (p < 0.001) at the 16th week. CONCLUSION: We conclude that NOS II inhibitor
      reduced the elevation of CAP thresholds in experimentally induced endolymphatic
      hydrops.

PMID- 17031326
TI  - Dental charity work--does it really help?

PMID- 17031327
TI  - A powerful stance.

PMID- 17031328
TI  - Competency based surgery.

PMID- 17031329
TI  - Fee-splitting.

PMID- 17031330
TI  - Supplying demand.

PMID- 17031331
TI  - Catastrophic occlusion.

PMID- 17031332
TI  - The Pareto principle.

PMID- 17031340
TI  - Urgent attention needed for Filipino children.

PMID- 17031343
TI  - Amazonian dental adventure.

PMID- 17031342
TI  - Dentists increase earnings from private work.

PMID- 17031344
TI  - Impression techniques for implant dentistry.
AB  - The object of making an impression in implant dentistry is to accurately relate
      an analogue of the implant or implant abutment to the other structures in the
      dental arch. This is affected by use of an impression coping which is attached to
      the implant or implant abutment. This impression coping is incorporated in an
      impression - much as a metal framework is 'picked up' in a remount impression for
      fixed prosthodontics. With implant copings the coping is usually attached to the
      implant or abutment with screws. The impression material used is usually an
      elastomeric impression material; the two types most widely used and shown to be
      the most appropriate are polyether and polyvinyl siloxane impression materials.

PMID- 17031351
TI  - The effect of social demographic factors, snack consumption and vending machine
      use on oral health of children living in London.
AB  - OBJECTIVE: To investigate the effect of socio-economic status, sugar, snack
      consumption and vending machine use on the prevalence and severity of caries
      (DMF) in children. DESIGN: An observational study was carried out in a dental
      practice in inner city London. Sixty children were asked to complete a
      questionnaire and a three day food and drink diary. After a dental examination
      the number of decayed (D), missing (M) or filled (F) teeth provided a DMF score.
      Anova and Pearsons correlations were used to analyse the data statistically.
      RESULTS: Children from social groups I and II consumed significantly less (P <
      0.05) sugar, confectionery, crisps and used a vending machine less often than
      children from other social groups. Children from Social groups I, II and III had
      significantly lower DMF scores. The average DMF from social group I children was
      0.5 +/- 0.6, whilst group IV children had the greatest incidence and a DMF of 4.6
      +/- 0.8. Significant correlations were identified between DMF and sugar,
      confectionery and crisp consumption and vending machine use, and a negative
      correlation between DMF and vegetable consumption. CONCLUSIONS: Socio-economic
      status and access to vending machines were found to have a significant effect on
      sugar intakes, foods choices, and dental health. The removal of vending machines
      from schools or at least installing 'healthy' vending machines is recommended.
      Health promotion programmes that account for social groups and snacking habits
      that are cost effective are required.

PMID- 17031352
TI  - Erosion of enamel by non-carbonated soft drinks with and without toothbrushing
      abrasion.
AB  - OBJECTIVE: To investigate how enamel loss due to erosion, and due to cycling of
      erosion and abrasion, depends on compositional parameters of soft drinks, and
      particularly whether the thickness of the erosive softened layer is a function of
      drink composition. SETTING: University dental hospital research laboratory in the
      UK, 2004. MATERIALS AND METHODS: Six drinks were chosen based on their popularity
      and composition: apple juice, orange juice, apple drink, orange drink, cranberry
      drink and 'ToothKind' blackcurrant drink. Group A samples (n = 36) were exposed
      to soft drinks at 36 degrees C for six consecutive 10 minute periods. Group B
      samples (n = 36) were subjected to alternating erosion and toothbrushing,
      repeated six times. Enamel loss was measured using optical profilometry. RESULTS:
      Group A: significant enamel loss was seen for all drinks (p < 0.001). Erosion was
      correlated with pH and calcium concentration but not phosphate concentration or
      titratable acidity. Group B: significant additional material loss due to
      toothbrush abrasion occurred with all drinks. Abrasive enamel loss differed
      between the drinks and was positively correlated with drink erosive potential.
      CONCLUSION: Enamel loss by erosion is exacerbated by subsequent abrasion. The
      amount of softened enamel removed by toothbrushing is a function of the chemical
      composition of the erosive medium.

PMID- 17031353
TI  - Sedation in Wales: a questionnaire.
AB  - AIM: To identify the current provision of sedation in primary dental care in
      Wales. DESIGN: Postal questionnaire survey. SETTING: Wales 2003. SUBJECTS AND
      MATERIALS: Questionnaires were sent to all dentists appearing on the Dentists
      Register with addresses in Wales (n = 1374). The questionnaires sought details on
      personal status, use of and training in conscious sedation techniques. RESULTS:
      In total 951 (69%) questionnaires were returned, 720 (90%) respondents worked in
      a primary dental care setting. Only 87 (12.1%) primary care dentists offered some
      form of sedation. CONCLUSIONS: The provision of conscious sedation services in
      primary dental care in Wales is poor.

PMID- 17031354
TI  - Archaeological evidence for dental innovation: an eighteenth century porcelain
      dental prosthesis belonging to Archbishop Arthur Richard Dillon.
AB  - During archaeological investigation by Gifford of St Pancras Old Church burial
      ground, on the eastern edge of Somers Town, London, in advance of construction of
      the new London terminus for the Channel Tunnel Rail Link, a full porcelain
      denture was discovered. The high quality porcelain dentures, manufactured in the
      late eighteenth century French style, may have been brought with their owner,
      Archbishop Arthur Richard Dillon, on his journey into exile. There is evidence of
      prolonged use, not only for cosmetic or vocal functions but also in mastication.
      The dentures are unique archaeological artefacts and represent a pivotal time in
      dental history, with the adoption of new materials and methods of manufacture.
      They reflect a period of significant social and economic change for the upper
      echelons of French society. This paper outlines the development of porcelain
      dentures, discusses the prosthesis, their owner, and a possible provenance.

PMID- 17031368
TI  - Dentistry--thinking outside the box.
AB  - For Liz Robb, returning to the UK after 25 years away meant a return to the
      dental career she thought she'd long since left behind. Here she explains how a
      chance look at an advertisement led her to a course that would broaden her
      outlook and give her the opportunity to progress in ways she never thought
      possible.

PMID- 17031369
TI  - Subspecialty certification in urology: a US perspective.

PMID- 17031370
TI  - Determining the prognosis of patients with renal cell carcinoma: is it time for a
      re-evaluation?

PMID- 17031371
TI  - Can TRUS guidance reduce the incidence of positive margins during laparoscopic
      radical prostatectomy?

PMID- 17031372
TI  - PSA level changes over time in men with an initial PSA level of < or = 4 ng/ml.

PMID- 17031373
TI  - Individualized assessment of prostate cancer risk.

PMID- 17031374
TI  - Early markers of metabolic syndrome in nonoverweight, middle-aged men.

PMID- 17031375
TI  - Improving cancer detection by prostate biopsy: the role of core number and site.

PMID- 17031376
TI  - Testosterone levels in benign prostatic hyperplasia: sexual function and response
      to therapy with dutasteride.

PMID- 17031377
TI  - Are bladder cancer patients with pT0 disease following radical cystectomy cured
      of cancer?

PMID- 17031378
TI  - Interpreting the international trends in testicular seminoma and nonseminoma
      incidence.
AB  - There are considerable geographic, ethnic and temporal variations in the global
      incidence of testicular cancer. The disease mainly affects Western populations,
      with average rates in developed areas of the world six times higher than those in
      developing areas. About 500,000 new cases were diagnosed worldwide in 2002, with
      the vast majority being germ cell tumors and occurring in young adult males.
      Traditionally, these tumors are further classified into seminoma and nonseminoma.
      In this Review, trends in the incidence of germ cell tumors are examined using
      high-quality cancer-registry data from 41 populations within 14 countries
      worldwide. To assess whether trends of seminoma and nonseminoma incidence are
      similar, data were analyzed by birth cohort. These analyses should reveal similar
      trends if the 10-year difference in the clinical manifestation of cancer between
      subtypes is caused by differences in the speed of progression from the same early
      rate-limiting step to the onset of symptomatic disease. In each country,
      incidence has uniformly increased in successive generations born from around 1920
      until very recently. Cohort-specific trends in seminoma incidence are similar to
      cohort-specific trends in nonseminoma incidence, lending support to the
      conclusion that the subtypes are epidemiologically and etiologically comparable.
      The findings presented are related to current theories and evidence regarding the
      determinants of testicular germ cell cancer.

PMID- 17031379
TI  - Recommendations for urodynamic assessment in the evaluation of women with stress
      urinary incontinence.
AB  - Urinary incontinence is a common problem that is experienced by women of all
      ages. The overall evaluation and treatment of incontinence has increased in
      sophistication, both as a result of the introduction of urodynamic testing in the
      assessment of patients, and because there are increasing numbers of medical and
      surgical treatments available for incontinence. What was previously considered a
      personal problem for women, and which was rarely discussed, has become a more
      open and acceptable complaint for female patients to bring to their physicians.
      This Review aims to clarify when urodynamic testing is clearly indicated for
      patients with symptoms of stress urinary incontinence, and describes the current
      recommendations from three national and international governing bodies. This
      Review will also highlight some of the ongoing debates over the performance,
      interpretation, and utility of urodynamic testing, and provide references for
      further reading on these topics.

PMID- 17031380
TI  - Primer: diagnosis and management of uncomplicated daytime wetting in children.
AB  - Functional daytime wetting is a common source of pediatric urologic complaints.
      Evaluation typically begins in the office setting. In contrast to the adult
      population, where an inability to maintain voiding control is virtually always
      considered pathologic, the evaluation of urinary incontinence in children must
      occur within the context of the child's developmental age. Functional
      incontinence refers to cases of urinary incontinence in which no structural or
      neurologic abnormality can be identified. The underlying etiologic mechanisms are
      heterogeneous, and include disorders of both the storage and voiding phases of
      the bladder cycle. Optimal treatment of functional daytime wetting depends on an
      accurate determination of the underlying etiology. Therapeutic options include
      behavior modification, medication, and aggressive treatment of comorbid
      conditions such as urinary infection and constipation.

PMID- 17031381
TI  - Hypogonadotropism with elevated serum testosterone: reversible causes of
      secondary infertility.
AB  - BACKGROUND: A 33-year-old man presented with secondary infertility, increased
      libido, and extreme oligospermia. Testicular volumes were reduced, but no
      gynecomastia was apparent and androgen abuse was denied. INVESTIGATIONS: Physical
      examination, semen-volume and sperm-density assessment, laboratory tests for
      serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone,
      and dehydroepiandrosterone sulfate, karyotyping, testicular ultrasound, pelvic
      and abdominal CT, assessment for serum testicular tumor markers (alpha
      fetoprotein and human chorionic gonadotropin), and histologic examination of
      testicular tissue. DIAGNOSIS: Benign Leydig-cell adenoma. MANAGEMENT: Left
      orchidectomy.

PMID- 17031382
TI  - Species and response dependent differences in the effects of MAPK inhibitors on
      P2X(7) receptor function.
AB  - BACKGROUND: Recent studies have implicated the mitogen activated protein kinase
      (MAPK) in cellular permeability changes following P2X(7) receptor activation in
      native tissues. In this study we have further studied the effect of MAPK
      inhibitors on recombinant and native P2X(7) receptors. EXPERIMENTAL APPROACH: The
      MAPK inhibitors SB-203580, SB-202190 and SB-242235 were examined in HEK293 cells
      expressing recombinant P2X(7) receptors and in THP-1 cells expressing native
      human P2X(7) receptors using a range of experimental approaches. KEY RESULTS: At
      human recombinant P2X(7) receptors, SB-203580 and SB-202190 were weak, non
      competitive inhibitors (pIC(50)= 4.8 - 6.4) of ethidium accumulation stimulated
      by 2'- & 3'-O-(4benzoylbenzoyl)-ATP (BzATP) but SB-242235 (0.1-10 microM) had no
      effect. SB-203580 and SB-202190 had no effect on rat or mouse recombinant P2X(7)
      receptors and studies with chimeric P2X(7) receptors suggested that SB-203580 was
      only effective in chimeras containing the N-terminal 255aa of the human P2X(7)
      receptor. SB-203580 did not consistently affect BzATP-mediated increases in cell
      calcium levels and, in electrophysiological studies, it slightly decreased
      responses to 30 microM BzATP but potentiated responses to 100 microM BzATP. In
      THP1 cells, SB-203580 modestly inhibited BzATP-stimulated ethidium accumulation
      (pIC(50) 5.7 - < 5) but SB-202190 had no effect. Finally, SB-203580 did not block
      BzATP-stimulated interleukin-1beta release in THP-1 cells. CONCLUSIONS: This
      study confirms that high concentrations of SB-203580 and SB-202190 can block
      human P2X(7) receptor-mediated increases in cellular ethidium accumulation but
      suggest this is not related to MAPK inhibition. Overall, the data cast doubt on a
      general role of MAPK in mediating P2X(7) receptor mediated changes in cellular
      permeability.

PMID- 17031383
TI  - Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular
      contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta.
AB  - BACKGROUND AND PURPOSE: The effect of lysophosphatidylcholine (LPC) on aortic
      contractions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic
      model, was studied. EXPERIMENTAL APPROACH: Using OLETF rats and control (Long
      Evans Tokushima Otsuka (LETO)) rats, the effects of LPC on the contractions
      induced by high-K(+) (10-40 mM), UK14,304 (10 approximately 100 nM; a selective
      alpha(2)-adrenoceptor agonist) and sodium orthovanadate (SOV; 10 microM
      approximately 3 mM) in endothelium-denuded aortae were compared. Aortic ERK
      activity and the mRNA expression for GPR4 (a putative LPC receptor) were also
      measured. KEY RESULTS: OLETF rats exhibited (vs. age-matched LETO rats): (1)
      greater potentiation of high-K(+)-induced contraction by 10 microM LPC - a
      potentiation attenuated by 10 microM genistein, protein tyrosine kinase (PTK)
      inhibitor, (2) greater potentiation of UK14,304 (10 approximately 100 nM)-induced
      contractions by LPC (1 microM approximately 10 microM) - a potentiation
      attenuated by 10 microM genistein, 50 microM tyrphostin A23 (PTK inhibitor) or 10
      microM PD98059 (MEK 1/2 inhibitor), (3) greater basal and LPC (1 microM)-induced
      ERK activities, (4) greater basal and 100 nM UK14,304-stimulated ERK2 activities
      in both the absence and presence of 10 microM LPC, (5) greater SOV (10 microM
      approximately 3 mM)-induced contractions, (6) greater potentiation of SOV-induced
      contractions by 10 microM LPC - a potentiation suppressed by 10 microM PD98059 or
      10 microM genistein, (7) upregulation of GPR4 mRNA. CONCLUSIONS AND IMPLICATIONS:
      These results suggest that the LPC-induced potentiation of contractions in the
      OLETF rat aorta may be attributable to increased PTKs or ERK activity and/or to
      receptor upregulation.

PMID- 17031384
TI  - Mitochondria, the calcium uniporter, and reperfusion-induced ventricular
      fibrillation.
AB  - The role of the mitochondria, and in particular the calcium (Ca) uniporter, in
      mediating reperfusion-induced arrhythmias is a novel investigative area. This
      commentary assesses the importance of a new article on this topic, published in
      this issue of the journal. Ventricular arrhythmogenesis remains an important area
      of research in the search of novel targets. The article by Garcia-Rivas et al in
      this issue represents a possible novel focus for investigation.

PMID- 17031385
TI  - Characterization of a selective and potent antagonist of human P2X(7) receptors,
      AZ11645373.
AB  - BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a
      role in several inflammatory processes, making it an attractive target for anti
      inflammatory drug discovery. We have recently identified a novel set of cyclic
      imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human
      macrophage THP-1 cells. In this study the actions and selectivity of one of these
      compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured
      membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing
      individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from
      THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP).
      KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on
      membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2),
      human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in
      HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a
      non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean
      values not significantly different between assays. K (B) values were not altered
      by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from
      lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90
      nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor
      mediated currents with less than 50% inhibition occurring at 10 microM.
      CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent
      antagonist at human but not rat P2X(7) receptors and will have much practical
      value in studies of human cells.

PMID- 17031386
TI  - Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post
      ischaemic functional recovery in rats in vivo.
AB  - BACKGROUND AND PURPOSE: The mitochondrial permeability transition pore (mPTP), an
      energy-dissipating channel activated by calcium, contributes to reperfusion
      damage by depolarizing the mitochondrial inner membrane potential. As
      mitochondrial Ca(2+) overload is a main inductor of mPTP opening, we examined the
      effect of Ru(360), a selective inhibitor of the mitochondrial calcium uptake
      system against myocardial damage induced by reperfusion in a rat model.
      EXPERIMENTAL APPROACH: Myocardial reperfusion injury was induced by a 5-min
      occlusion of the left anterior descending coronary artery, followed by a 5-min
      reperfusion in anaesthetized open-chest rats. We measured reperfusion-induced
      arrhythmias and functions indicative of unimpaired mitochondrial integrity to
      evaluate the effect of Ru(360) treatment. KEY RESULTS: Reperfusion elicited a
      high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial
      integrity. A bolus intravenous injection of Ru(360) (15-50 nmol kg(-1)), given 30
      min before ischaemia, significantly improved the above mentioned variables in the
      ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from
      Ru(360)-treated ventricles was partially diminished, suggesting an interaction of
      this compound with the calcium uniporter. CONCLUSIONS AND IMPLICATIONS: We showed
      that Ru(360) treatment abolishes the incidence of arrhythmias and haemodynamic
      dysfunction elicited by reperfusion in a whole rat model. Ru(360) administration
      partially inhibits calcium uptake, preventing mitochondria from depolarization by
      the opening of the mPTP. We conclude that myocardial damage could be a
      consequence of failure of the mitochondrial network to maintain the membrane
      potential at reperfusion. Hence, it is plausible that Ru(360) could be used in
      reperfusion therapy to prevent the occurrence of arrhythmia.

PMID- 17031387
TI  - Iron is not involved in oxidative stress-mediated cytotoxicity of doxorubicin and
      bleomycin.
AB  - BACKGROUND AND PURPOSE: The anticancer drugs doxorubicin and bleomycin are well
      known for their oxidative stress-mediated side effects in heart and lung,
      respectively. It is frequently suggested that iron is involved in doxorubicin and
      bleomycin toxicity. We set out to elucidate whether iron chelation prevents the
      oxidative stress-mediated toxicity of doxorubicin and bleomycin and whether it
      affects their antiproliferative/proapoptotic effects. EXPERIMENTAL APPROACH: Cell
      culture experiments were performed in A549 cells. Formation of hydroxyl radicals
      was measured in vitro by electron paramagnetic resonance (EPR). We investigated
      interactions between five iron chelators and the oxidative stress-inducing agents
      (doxorubicin, bleomycin and H(2)O(2)) by quantifying oxidative stress and
      cellular damage as TBARS formation, glutathione (GSH) consumption and lactic
      dehydrogenase (LDH) leakage. The antitumour/proapoptotic effects of doxorubicin
      and bleomycin were assessed by cell proliferation and caspase-3 activity assay.
      KEY RESULTS: All the tested chelators, except for monohydroxyethylrutoside
      (monoHER), prevented hydroxyl radical formation induced by H(2)O(2)/Fe(2+) in EPR
      studies. However, only salicylaldehyde isonicotinoyl hydrazone and deferoxamine
      protected intact A549 cells against H(2)O(2)/Fe(2+). Conversely, the chelators
      that decreased doxorubicin and bleomycin-induced oxidative stress and cellular
      damage (dexrazoxane, monoHER) were not able to protect against H(2)O(2)/Fe(2+).
      CONCLUSIONS AND IMPLICATIONS: We have shown that the ability to chelate iron as
      such is not the sole determinant of a compound protecting against doxorubicin or
      bleomycin-induced cytotoxicity. Our data challenge the putative role of iron and
      hydroxyl radicals in the oxidative stress-mediated cytotoxicity of doxorubicin
      and bleomycin and have implications for the development of new compounds to
      protects against this toxicity.

PMID- 17031391
TI  - The effect of 6 months supplementation with conjugated linoleic acid on insulin
      resistance in overweight and obese.
AB  - BACKGROUND: Contradicting results have been published regarding the effect of
      conjugated linoleic acid (CLA) on insulin resistance. However, only a few studies
      have used the euglycemic hyperinsulinemic clamp method, which is considered the
      standard for measuring insulin resistance. OBJECTIVE: To evaluate if CLA as a
      mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the
      insulin resistance in healthy overweight and obese male and female adults.
      DESIGN: The main study was a randomized, double-blind, placebo-controlled trial
      with change in body composition as primary end point comprising 118 subjects
      receiving supplementation with either placebo (olive oil) or CLA (Clarinol) for 6
      months. A sub-population of 49 subjects agreed additionally to participate in an
      euglycemic hyperinsulinemic clamp study at baseline and after 6 months of
      supplementation with study drug. The primary outcome was the change in glucose
      uptake (M) as measured by the hyperinsulinemic euglycemic glucose clamp method.
      Secondary outcomes were the correlates between insulin resistance and changes in
      body composition or blood chemistry parameters. Forty-one subjects completed the
      clamp test at both time points. RESULTS: The median M of the CLA group was 11.0
      mg min(-1) lean body mass (lbm)(-1) (n=24) at baseline, 10.3 mg min(-1) lbm(-1)
      (n=24) after 6 months, and the median difference was +0.21 mg min(-1) lbm(-1)
      (n=24). The median M of placebo group was 8.4 mg min(-1) lbm(-1) at baseline and
      9.3 mg min(-1) lbm(-1) after 6 months and the median difference was -0.22 mg min(
      1) lbm(-1) (n=17). No significant (P<0.05) differences were found within groups
      or between groups. Likewise, the glucose uptake insulin concentration ratio
      during clamp (M/I) was independent of treatment and time. Homeostasis model
      assessment (HOMA) and quantitative insulin sensitivity check index derived from
      fasting glucose and insulin were also independent of treatment and time, and HOMA
      for the clamp population (n=49) corresponded well with HOMA for the per protocol
      population (n=83). Correlation analysis showed that changes in M were inversely
      correlated to changes in glucohemoglobin (P=0.002), but did not correlate with
      changes in either glucose, insulin, insulin c-peptide, leptin, adiponectin or
      percent body fat. CONCLUSIONS: CLA does not affect glucose metabolism or insulin
      sensitivity in a population of overweight or obese volunteers.

PMID- 17031388
TI  - Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle:
      a biochemical, histological and electrophysiological study.
AB  - BACKGROUND AND PURPOSE: Skeletal muscle injury by hypolipidemic drugs is not
      fully understood. An extensive analysis of the effect of chronic treatment with
      fluvastatin (5 mgkg(-1) and 20 mgkg(-1)), atorvastatin (10 mgkg(-1)) and
      fenofibrate (60 mgkg(-1)) on rat skeletal muscle was undertaken. EXPERIMENTAL
      APPROACH: Myoglobinemia as sign of muscle damage was measured by enzymatic assay.
      Histological and immunohistochemical techniques were used to estimate muscle
      integrity and the presence of aquaporin-4, a protein controlling water
      homeostasis. Electrophysiological evaluation of muscle Cl(-) conductance (gCl)
      and mechanical threshold (MT) for contraction, index of intracellular calcium
      homeostasis, was performed by the two-intracellular microelectrodes technique.
      KEY RESULTS: Fluvastatin (20 mgkg(-1)) increased myoglobinemia. The lower dose of
      fluvastatin did not modify myoglobinemia, but reduced urinary electrolytes,
      suggesting direct effects on renal function. Atorvastatin also increased
      myoglobinemia, with slight effects on urinary parameters. No treatment caused any
      histological damage to muscle or modification in the number of fibres expressing
      aquaporin-4. Either fluvastatin (at both doses) or atorvastatin reduced
      sarcolemma gCl and changed MT. Both statins produced slight effects on total
      cholesterol, suggesting that the observed modifications occur independently of
      HMGCoA-reductase inhibition. Fenofibrate increased myoglobinemia and decreased
      muscle gCl, whereas it did not change the MT, suggesting a different mechanism of
      action from the statins. CONCLUSIONS AND IMPLICATIONS: This study identifies
      muscle gCl and MT as early targets of drugs action that may contribute to milder
      symptoms of myotoxicity, such as muscle cramps, while the increase of
      myoglobinemia is a later phenomenon.

PMID- 17031389
TI  - A rabbit Langendorff heart proarrhythmia model: predictive value for clinical
      identification of Torsades de Pointes.
AB  - BACKGROUND AND PURPOSE: The rabbit isolated Langendorff heart model (SCREENIT)
      was used to investigate the proarrhythmic potential of a range of marketed drugs
      or drugs intended for market. These data were used to validate the SCREENIT model
      against clinical outcomes. EXPERIMENTAL APPROACH: Fifty-five drugs, 3 replicates
      and 2 controls were tested in a blinded manner. Proarrhythmia variables included
      a 10% change in MAPD(60), triangulation, instability and reverse frequency
      dependence of the MAP. Early after-depolarisations, ventricular tachycardia, TdP
      and ventricular fibrillation were noted. Data are reported at nominal
      concentrations relative to EFTPC(max). Proarrhythmic scores were assigned to each
      drug and each drug category. KEY RESULTS: Category 1 and 2 drugs have the highest
      number of proarrhythmia variables and overt proarrhythmia while Category 5 drugs
      have the lowest, at every margin. At 30-fold the EFTPC(max), the mean
      proarrhythmic scores are: Category 1, 101+/-24; Category 2, 101+/-14; Category 3,
      72+/-20; Category 4, 59+/-16 and Category 5, 22+/-9 points. Only drugs in
      Category 5 have mean proarrhythmic scores, below 30-fold, that remain within the
      Safety Zone. CONCLUSIONS AND IMPLICATIONS: A 30-fold margin between effects and
      EFTPC(max) is sufficiently stringent to provide confidence to proceed with a new
      chemical entity, without incurring the risk of eliminating potentially beneficial
      drugs. The model is particularly useful where compounds have small margins
      between the hERG IC(50) and predicted EFTPC(max). These data suggest this is a
      robust and reliable assay that can add value to an integrated QT/TdP risk
      assessment.

PMID- 17031392
TI  - Hemicentins: what have we learned from worms?
AB  - Hemicentins are conserved extracellular matrix proteins discovered in
      Caenorhabditis elegans, with orthologs in all vertebrate species including human
      and mouse. Hemicentins share a single, highly conserved amino-terminal von
      Willebrand A domain, followed by a long (>40) stretch of immunoglobulin repeats,
      multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal
      module. C. elegans has a single hemicentin gene that has pleiotropic functions in
      transient cell contacts that are required for cell migration and basement
      membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions
      and elastic fiber-like structures. Here, we summarize what is known about the
      function of hemicentin in C. elegans and discuss implications for hemicentin
      function in other species.

PMID- 17031393
TI  - Transgenic expression of DwMYB2 impairs iron transport from root to shoot in
      Arabidopsis thaliana.
AB  - In plant, iron uptake and homeostasis are tightly regulated to ensure its
      absorption from soil and to avoid excess iron in the cell. Many genes involved in
      this process have been identified during past several years, but there are many
      problems remain unsolved in the genetic regulation of whole plant iron
      trafficking and allocation. MYB transcription factors contain tandem repeats of a
      approximately 50 amino acid DNA-binding motif (R) and are involved in the
      regulation of many aspects of plant development, hormone signaling and
      metabolism. Here, we report that the ectopic expression of orchid R2R3-MYB gene
      DwMYB2 in Arabidopsis thaliana confers the transgenic plants hypersensitivity to
      iron deficiency. In DwMYB2 transgenic plants, the iron content in root is two
      fold higher compared to that in wild-type root, while the reverse is true in
      shoot. This imbalance of iron content in root and shoot suggested that the
      translocation of iron from root to shoot was affected by the expression of DwMYB2
      in the transgenic plants. Consistently, gene chip and reverse transcription
      polymerase chain reaction analysis revealed that the ferric-chelate reductase
      gene, AtFRO2, and the iron transporter gene, AtIRT1 and AtIRT2, are up-regulated
      by DwMYB2 expression, while other potential iron transporters such as AtIREG1,
      AtFRD3 and NRAMP1 are down-regulated. In addition, the expression of several
      putative peptide transporters and transcription factors are also altered in the
      35S::DwMYB2 transgenic lines. These data provide us insight into the whole plant
      translocation of iron and identify candidate genes for iron homeostasis in plants
      despite the fact that a heterologous gene was expressed.

PMID- 17031394
TI  - Second primary cancer in survivors following concurrent chemoradiation for
      locally advanced non-small-cell lung cancer.
AB  - Long-term cancer survivors risk development of second primary cancers (SPC).
      Vigilant follow-up may be required. We report outcomes of 92 patients who
      underwent chemoradiation for unresectable stage III non-small-cell lung cancer,
      with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100
      patient-years (95% confidence interval: 1.0-4.9).

PMID- 17031395
TI  - The role of MYH and microsatellite instability in the development of sporadic
      colorectal cancer.
AB  - Biallelic germline mutations in MYH are associated with colorectal neoplasms,
      which develop through a pathway involving somatic inactivation of APC. In this
      study, we investigated the incidence of the common MYH mutations in an Australian
      cohort of sporadic colorectal cancers, the clinicopathological features of MYH
      cancers, and determined whether inactivation of mismatch repair and base excision
      repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte
      DNA of 872 colorectal cancer patients and 478 controls. Two compound
      heterozygotes were identified in the cancer population and all three cancers from
      these individuals displayed a prominent infiltration of intraepithelial
      lymphocytes. In total, 11 heterozygotes were found in the cancer group and five
      in the control group. One tumour from an individual with biallelic germline
      mutation of MYH also demonstrated microsatellite instability (MSI) as a result of
      biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers
      are rare in a sporadic colorectal population, this study shows that these tumours
      can develop through either a chromosomal or MSI pathway. Tumours arising in the
      setting of BER or mismatch repair deficiency may share a biological
      characteristic, which promotes lymphocytic infiltration.

PMID- 17031396
TI  - Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose
      ifosfamide, high-dose doxorubicin and salvage therapies.
AB  - Having determined in a phase I study the maximum tolerated dose of high-dose
      ifosfamide combined with high-dose doxorubicin, we now report the long-term
      results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients
      with locally advanced or metastatic soft-tissue sarcomas were included, with age
      <60 years and all except one in good performance status (0 or 1). The
      chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion
      for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna
      and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A
      median of 4 (1-6) cycles per patient was administered. Twenty-two patients
      responded to therapy, including three complete responders and 19 partial
      responders for an overall response rate of 48% (95% CI: 33-63%). The response
      rate was not different between localised and metastatic diseases or between
      histological types, but was higher in grade 3 tumours. Median overall survival
      was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in
      43% of patients and found to be the most significant predictor for favourable
      survival (exploratory multivariate analysis). Haematological toxicity was severe,
      including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in
      27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient
      died of septic shock. This high-dose regimen is toxic but nonetheless feasible in
      multicentre settings in non elderly patients with good performance status. A high
      response rate was obtained. Prolonged survival was mainly a function of salvage
      therapies.

PMID- 17031397
TI  - A phase II clinical and pharmacodynamic study of temsirolimus in advanced
      neuroendocrine carcinomas.
AB  - Standard cytotoxic treatments for neuroendocrine tumours have been associated
      with limited activity and remarkable toxicity. A phase II study was designed to
      evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients
      with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced
      progressive NEC received intravenous weekly doses of 25 mg of temsirolimus.
      Patients were evaluated for tumour response, time to progression (TTP), overall
      survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as
      13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus
      were assessed for potential predictive and correlative markers. The intent-to
      treat response rate was 5.6% (95% CI 0.6-18.7%), median TTP 6 months and 1-year
      OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of
      patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%).
      Temsirolimus effectively inhibited the phosphorylation of S6 (P=0.02). Higher
      baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P=0.01)
      predicted for a better response. Increases in pAKT (P=0.041) and decreases in
      pmTOR (P=0.048) after treatment were associated with an increased TTP.
      Temsirolimus appears to have little activity and does not warrant further single
      agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective
      mTOR pathway downregulation.

PMID- 17031398
TI  - Survival trends for small intestinal cancer in England and Wales, 1971-1990:
      national population-based study.
AB  - This population-based study examines prognostic factors and survival trends among
      adults (15-99 years) diagnosed with small intestinal cancer in England and Wales
      during 1971-1990 and followed up to 1995. During this period, the 1- and 5-year
      age-standardised relative survival rates for small intestinal cancers combined
      were 42% and 23%, respectively. Duodenal tumours, adenocarcinomas, men, patients
      with advanced age and the most deprived patients had the poorest prognosis. For
      all small bowel tumours combined, the excess risk of death fell significantly by
      6-9% every 4 years over the 20-year period (adjusted excess hazard ratio (EHR)
      0.91 at 1 year after diagnosis, 0.94 at 5 years). For duodenal tumours, the EHR
      fell by about 14% (95% CI 5-22%) every 4 years between 1979 and 1990, and a
      similar trend for jejunal tumours was of borderline significance. Further
      population-based investigations linking survival data to individual data on
      diagnostic methods and types of treatment are needed.

PMID- 17031399
TI  - The significance of the time interval between antecedent pregnancy and diagnosis
      of high-risk gestational trophoblastic tumours.
AB  - It is thought that the time interval between the antecedent pregnancy and
      diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome
      of these patients. In this study, we investigate the significance of this time
      interval. Multivariate analysis was used to investigate if the time interval was
      of prognostic significance from our cohort of 241 high-risk patients with GTT.
      Subsequent cutpoint analysis was used to determine an optimal cutpoint for the
      interval covariate. The outcome of these patients was plotted according to the
      Kaplan-Meier method. The time interval was of prognostic significance on
      multivariate analysis. A period of greater than 2.8 years after pregnancy was
      found to be of most significance. The 5-year overall survival was 62.0% (95% CI:
      47-76%) for greater than 2.8 years vs 94% (95% CI: 91-97%) for less than 2.8
      years (P<0.001). Multivariate analysis showed the presence of liver metastasis
      and the number of metastasis was also of prognostic importance. The interval
      between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic
      significance. This gives some insight into the pathogenesis of the disease.

PMID- 17031401
TI  - Incidence rate trends of histological subtypes of nasopharyngeal carcinoma in
      Hong Kong.
AB  - The overall decline in incidence rate of nasopharyngeal carcinoma in Hong Kong
      during 1988-2002 was limited primarily to a decrease in keratinising carcinoma,
      which could be explained by the decline in cigarette smoking. Genetic and Epstein
      Barr virus interactions may explain the relatively stable incidence rate of non
      keratinising carcinoma.

PMID- 17031400
TI  - Reduction of mitomycin C is catalysed by human recombinant NRH:quinone
      oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron
      donating co-factor.
AB  - NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic
      activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron
      donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a
      mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2
      catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction
      results in species that inhibit the NQO2-mediated metabolism of CB1954. In
      addition, MMC caused an increase in DNA cross-links in a cell line transfected to
      overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1
      expressing cell line. These data indicate that NQO2 may contribute to the
      metabolism of MMC to cytotoxic species.

PMID- 17031402
TI  - A specific cadherin phenotype may characterise the disseminating yet non
      metastatic behaviour of pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin,
      characterised by excess intra-abdominal mucin production leading to high
      morbidity and mortality. While histological features are frequently indolent,
      this tumour disseminates aggressively throughout the abdominal cavity, yet seldom
      metastasises. This study determined the expression of several markers of
      colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20
      and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9
      (IL-9), IL-9 receptor (IL-9Ralpha)), and cell adhesion (N- and E-cadherin,
      vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa
      (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins
      were similar for PMP as those in colorectal adenocarcinomas with the exception
      that the CK20-/CK7- pattern was rare in PMP (Fisher's exact test: P=0.001).
      Similarly, expressions of mucin-related proteins were comparable for
      adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in
      adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern
      of adhesion-related protein expressions of increased N-cadherin, reduced E
      cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible
      epithelial-mesenchymal transition state. Primary PMP cell cultures were
      successfully maintained and demonstrated marker expressions similar to those seen
      in in vivo tissues. These early characterisation studies demonstrate similarities
      between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin
      phenotype that may characterise the distinct non-metastasising behaviour of PMP,
      and form the basis for future mechanistic and therapy-targeting research.

PMID- 17031403
TI  - Perioperative immunomodulation with interleukin-2 in patients with renal cell
      carcinoma: results of a controlled phase II trial.
AB  - We conducted a non-randomised controlled phase II trial to investigate the role
      of preoperative administration of interleukin-2 (IL-2) in patients with renal
      cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients
      were allocated alternately to the two study groups: perioperative
      immunomodulation with IL-2 (IL-2 group; n=60) and perioperative immunomonitoring
      without immunomodulation (control group; n=60). Patients from the IL-2 group
      received four doses of 10 x 10(6) IU m(-2) twice daily subcutaneously a week
      before operation followed by a daily maintenance dose of 3 x 10(6) IU m(-2)
      subcutaneously until a day before the operation. Parameters of cellular and
      humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker
      CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and
      CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34,
      as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist,
      transforming growth factor-beta1, and vascular endothelial growth factor) were
      measured in peripheral venous blood at various intervals. Interleukin-2-related
      toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period,
      T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and
      IL-10 increased. However, all these alterations were significantly less
      accentuated in patients who had been pretreated with IL-2. Median follow-up was
      40 months. Tumour-specific survival in the IL-2 group and the control group was
      98 vs 81% after 1 year and 86 vs 73% after 5 years (P=0.04). A similar effect was
      found for progression-free survival. We conclude that IL-2 can be safely
      administered in the perioperative period and modulates immunological parameters.
      However, to validate the survival data, a larger randomised phase III trial is
      needed.

PMID- 17031404
TI  - Genetic and metabolic predictors of chemosensitivity in oligodendroglial
      neoplasms.
AB  - The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms,
      but some with intact 1p/19q also respond and not all with 1p/19q loss derive
      durable benefit from chemotherapy. We have evaluated the predictive and
      prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in
      38 primary and 10 recurrent oligodendroglial neoplasms following PCV
      chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII
      and was associated with response (Fisher-Exact: P=0.000) and prolonged
      progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank:
      P=0.0048). Response was unrelated to metabolism, with tumours with high or low
      metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted
      shorter progression-free survival (PFS) in the series (log-rank: (201)Tl
      P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype.
      Elevated metabolism was associated with shorter OS in cases with intact 1p/19q
      (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders
      (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss
      were independent predictors of survival in multivariate analysis. In this initial
      study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be
      associated with poor survival following therapy irrespective of genotype. This
      may be clinically useful warranting further study.

PMID- 17031406
TI  - Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in
      metastatic renal cell carcinoma.
AB  - Immunotherapy is the only available treatment for metastatic renal cell cancer
      (RCC), but the response rate is only about 20% and the treatment is occasionally
      associated with severe adverse effects. Thus, the selection of patients with a
      high susceptibility to immunotherapy is needed; however, there is no promising
      molecular marker that can predict the response to immunotherapy for RCC. This
      study was carried out to elucidate the potential role of apoptosis-related
      molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI)
      as predictors of the susceptibility of metastatic RCC to immunotherapy.
      Immunohistochemical examination of tumour tissues from 40 patients with
      metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy
      was performed. Patients with progressive disease (PD) after immunotherapy
      presented with decreased survival (P=0.006). Progressive disease correlated with
      higher PI in the primary lesion (P=0.0087). All primary tumours of CR or PR
      patients were negative for Bcl-2, whereas among NC+PD patients, 40.6% were
      positive for Bcl-2 (P=0.0373). Patients in whom the primary tumours were both Bcl
      2- and Fas-negative showed significantly better responses to immunotherapy in
      comparison with the remaining group (P=0.0022). The Bcl-2 and Fas status of the
      primary lesion may become useful criteria for the selection of patients with
      metastatic RCC for immunotherapy.

PMID- 17031405
TI  - The role of socio-economic status in the decision making on diagnosis and
      treatment of oesophageal cancer in The Netherlands.
AB  - In the United States (USA), a correlation has been demonstrated between socio
      economic status (SES) of patients on the one hand, and tumour histology, stage of
      the disease and treatment modality of various cancer types on the other hand. It
      is unknown whether such correlations are also involved in patients with
      oesophageal cancer in The Netherlands. Between 1994 and 2003, 888 oesophageal
      cancer patients were included in a prospective database with findings on the
      diagnostic work-up and treatment of oesophageal cancer. Socio-economic status of
      patients was defined as the average net yearly income. Linear-by-linear
      association testing revealed that oesophageal adenocarcinoma was more frequently
      observed in patients with higher SES and squamous cell carcinoma in patients with
      lower SES (P=0.02). Multivariable logistic regression analysis showed no
      correlation between SES and staging procedures and preoperative TNM stage. The
      adjusted odds ratio (OR) for stent placement was 0.82 (95% CI 0.71-0.95),
      indicating that with an increase in SES by 1200 [euro], the likelihood that a
      stent was placed declined by 18%. Patients with a higher SES more frequently
      underwent resection or were treated with chemotherapy (OR: 1.15; 95% CI 1.01-1.32
      and OR: 1.16; 95% CI 1.02-1.32, respectively). Socio-economic factors are
      involved in oesophageal cancer in The Netherlands, as patients with a higher SES
      are more likely to have an adenocarcinoma and patients with a lower SES a
      squamous cell carcinoma. Moreover, the correlations between SES and different
      treatment modalities suggest that both patient and doctor determinants contribute
      to the decision on the most optimal treatment modality in patients with
      oesophageal cancer.

PMID- 17031407
TI  - Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of
      stage III colon cancer.
AB  - For many years, the standard treatment for stage III colon cancer has been
      surgical resection followed by 5-fluorouracil in combination with folinic acid (5
      FU/LV). Ongoing clinical trial evidence suggests that capecitabine and
      oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and
      overall survival when compared against 5-FU/LV alone in the adjuvant setting.
      This study evaluates the cost-effectiveness profiles of these two regimens in
      comparison to standard chemotherapy, using evidence from two international
      randomised controlled trials. Survival modelling techniques were employed to
      extrapolate survival curves from the two trials in order to estimate the long
      term benefits of alternative treatment options over the remaining lifetime of
      patients. The health economic analysis suggests that capecitabine is expected to
      produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in
      combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY
      gained when compared to 5-FU/LV alone. Future research should attempt to
      elucidate uncertainties concerning the optimal roles of capecitabine and/or
      oxaliplatin in the adjuvant setting in order to achieve the maximum level of
      clinical benefit.

PMID- 17031408
TI  - Vinflunine: a new active drug for second-line treatment of advanced breast
      cancer. Results of a phase II and pharmacokinetic study in patients progressing
      after first-line anthracycline/taxane-based chemotherapy.
AB  - To evaluate the single agent activity, pharmacokinetics and tolerability of the
      novel tubulin targeted agent vinflunine (VFL) (320 mg m(-2) q 21 days) as second
      line chemotherapy in patients with metastatic breast carcinoma (MBC). All
      patients had disease progression after anthracycline/taxane (A/T) therapy. They
      could have received a nonanthracycline adjuvant treatment and subsequently
      received a first-line A/T combination for advanced/metastatic disease; or
      relapsed >6 months after completion of adjuvant A/T therapy and were subsequently
      treated with the alternative agent; or relapsed within 6 months from an adjuvant
      A/T combination. Objective response was documented in 18 of 60 patients enrolled
      (RR: 30% (95% confidence interval (CI): 18.9-43.2%)). Among the responders, seven
      patients had relapsed during a period of <3 months from taxane-based regimen
      yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI:
      4.2-7.2), median progression-free survival was 3.7 months (95% CI: 2.8-4.2) and
      median overall survival was 14.3 months (95% CI: 9.2-19.6). The most frequent
      adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of
      patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of
      patients) and constipation (grade 3 in 11.7% of patients) were also common; these
      were non-cumulative and manageable permitting achievement of a good relative dose
      intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in
      the management of MBC patients previously treated with (A/T)-based regimens.
      These encouraging phase II results warrant further investigation of this novel
      agent in combination with other active agents in this setting or in earlier
      stages of disease.

PMID- 17031410
TI  - Remote monitoring of implantable cardioverter defibrillator.

PMID- 17031409
TI  - Mathematical models of targeted cancer therapy.
AB  - Improved understanding of the molecular underpinnings of cancer initiation and
      progression has led to the development of targeted cancer therapies. The
      importance of these new methods of cancer treatment necessitates further research
      into the dynamic interactions between cancer cells and therapeutic agents, as
      well as a means of analysing their relationship quantitatively. The present
      review outlines the application of mathematical modelling to the dynamics of
      targeted cancer therapy, focusing particular attention on chronic myeloid
      leukaemia and its treatment with imatinib (Glivec).

PMID- 17031411
TI  - Interference between cellular telephones and implantable rhythm devices: a review
      on recent papers.
AB  - BACKGROUND: Cardiac pacemakers and implantable defibrillators are potentially
      susceptible to electromagnetic interferences as they have complex circuitry for
      sensing and communication purposes. Cellular telephones being an important source
      of electromagnetic waves are likely to cause interference in the function of
      these devices. METHODS: A systematic analysis of studies on interaction between
      cellular telephones and implantable devices was done using professional databases
      for literature. Related articles and references of relevant articles were also
      searched for suitable studies. RESULTS: Fourteen studies on pacemakers and eight
      studies on implantable defibrillators were identified. No dangerous malfunction
      was found in any of the analyzed studies, but most of the studies noted
      interference with device function when the phone was operated very close to the
      device. Interference was minimally in those devices with built in feed-through
      filters for eliminating electromagnetic interference. Device programming and
      interrogation were the most susceptible phases of operation. SUMMARY: Cellular
      phones are likely to interfere with implantable rhythm devices if operated in
      close proximity or during programming of the device. Patients with implanted
      devices can safely use cellular phones if they are not carried close to the
      implanted devices or operated near them. Carrying the cellular phones in the belt
      position, receiving calls in the ear opposite to the side of the implanted device
      and keeping the phone as far away as possible while dialing can be considered a
      safe practice. Interrogation of the devices should take place exclusively in
      areas where utilization of cellular phones is strictly prohibited. Studies on
      pacemakers published in the current decade have shown much lesser rates of
      interference, possibly due to improvement in device technology.

PMID- 17031412
TI  - Shortening of ventriculoatrial interval after ablation of an accessory pathway.

PMID- 17031413
TI  - Narrow complex tachycardia with alternating R-R intervals. What is the mechanism?

PMID- 17031414
TI  - Stable atrial sensing on long-term follow up of VDD pacemakers.
AB  - BACKGROUND: The hemodynamic advantages of maintaining AV synchrony through AV
      synchronous pacing are widely known as compared to single chamber pacing. DDD
      pacemaker implantation entails higher cost and is technically more challenging
      than the VDD pacemaker. METHODS: Seventy one patients underwent VDD lead
      (Biotronik GmbH, St. Jude Medical and Medtronic Inc.) implantation at KEM
      hospital, Mumbai during a period of 3 years through subclavian, axillary and
      cephalic routes for degenerative, post-surgical or congenital high grade
      atrioventricular or complete heart block. They were followed up regularly for
      ventricular threshold and P wave amplitude of the floating atrial dipole.
      RESULTS: Follow up data of almost 95% of patients is available for a period of
      15.8 +/- 6.7 months. P wave amplitude at implant was 2.1 +/- 0.7mV and at follow
      up 1.1 +/- 0.6mV with mean ventricular threshold of <0.5V at implant and <1V at
      follow-up. CONCLUSION: Implantation of a single lead VDD pacemaker is possible in
      all patients with symptomatic AV block and intact sinus node function without any
      technical complications. P wave sensing is reliable and consistent with floating
      atrial lead at an average follow up of 15.8 months, providing an excellent
      alternative to DDD pacemaker implantation.

PMID- 17031415
TI  - Early outcomes of out-of-hospital cardiac arrest after early defibrillation: a 24
      months retrospective analysis.
AB  - INTRODUCTION: Cardiovascular disease remains the most common cause of death in
      the United States and most other Western nations. Among these deaths, sudden, out
      of-hospital cardiac arrest claims approximately 1000 lives each day in the United
      States alone. Most of these cardiac arrests are due to ventricular fibrillation.
      Though highly reversible with the rapid application of a defibrillator,
      ventricular fibrillation is otherwise fatal within minutes, even when
      cardiopulmonary resuscitation is provided immediately. The overall survival rate
      in the United States is estimated to be less than 5 percent. Recent developments
      in automated-external-defibrillator technology have provided a means of
      increasing the rate of prompt defibrillation after out-of-hospital cardiac
      arrest. After minimal training, nonmedical personnel (e.g., flight attendants and
      casino workers) are also able to use defibrillators in the workplace, with
      lifesaving effects. Nonetheless, such programs have involved designated personnel
      whose job description includes assisting persons who have had sudden cardiac
      arrest. Data are still lacking on the success of programs in which automated
      external defibrillators have been installed in public places to be used by
      persons who have no specific training or duty to act. MATERIALS AND METHODS: All
      patients who had an out-of-hospital cardiac arrest between January 2003 and
      December 2004 and who received early defibrillation for ventricular fibrillation
      were included. We conducted a 24 months retrospective population-based analysis
      of the outcome in our population. RESULTS: Over a 24 month period, 446 people had
      non-traumatic cardiac arrest, and in all of them it was observed to be
      ventricular fibrillation. In a very few cases, the defibrillator operators were
      good Samaritans, acting voluntarily. Eighty-nine patients (about 19%) with
      ventricular fibrillation were successfully resuscitated, including eighteen who
      regained consciousness before hospital admission. CONCLUSION: Automated external
      defibrillators deployed in readily accessible, well-marked areas, are really very
      effective in assisting patients with cardiac arrest. However, it's quite true
      that, in the cases of survivors, most of our users had good prior training in the
      use of these devices.

PMID- 17031416
TI  - Current developments in microvolt T-wave alternans.
AB  - Microvolt T-wave alternans (MTWA), the beat-to-beat fluctuation in T wave
      amplitude and morphology, is closely linked to vulnerability to ventricular
      arrhythmias in various experimental and clinical conditions. Clinically, MTWA is
      most commonly measured using the spectral method, although non-spectral methods
      for its assessment from ambulatory electrocardiographical recordings also have
      been developed. Recent studies suggest that the quantitative assessment of TWA
      may also be clinically relevant. The standardisation of the criteria for abnormal
      MTWA test still needs to be completed. The expansion of indications for
      implantable cardioverter-defibrillator (ICD) therapy following the positive
      results of the MADIT-II and SCD-HeFT trials might have unacceptable economic and
      medical consequences, and therefore new tests are needed to better discriminate
      patients who will and will not benefit from ICD implantation. A recent meta
      analysis of MTWA studies revealed an overall positive predictive value for
      arrhythmic events of 19.3%, negative predictive value of 97.2%, and 3.77%
      univariate relative risk of arrhythmic events. The negative predictive value of
      MTWA in MADIT-II type patients has been reported to be 97.5%. The predictive
      value of the test varied significantly in different patient population. Current
      data support the use of MTWA testing for evaluation of patients with low ejection
      fraction who are considered for ICD implantation. The independence of the
      prognostic value of MTWA from other clinical and electrophysiological variables
      needs further confirmation.

PMID- 17031417
TI  - Minimally invasive mapping guided surgical treatment of atrial fibrillation.
      Utopia or near future?
AB  - Isolation of the pulmonary veins has been used as surgical treatment for atrial
      fibrillation (AF) from the early 90s, as it was incorporated in the Maze
      procedure. With the evidence that triggers form this area can induce AF, the Maze
      III procedure has been adapted and modified towards a single lesion around the
      pulmonary veins for the treatment of paroxysmal and chronic AF in some centers.
      New ablation techniques with a diversity of energy sources further paved the way
      for less invasive procedures. Minimal invasive techniques to prevent major
      surgery may potentially make the treatment available for a patient population
      that do not have to undergo cardiac surgery for other reasons. Besides these
      technical developments, high density mapping can be used to identify the AF
      substrate in the individual patient and optimization of the treatment by local
      substrate guided ablation. This review aims to summarize the robotic and
      thoracoscopic techniques to isolate the pulmonary veins. Furthermore, it is
      discussed why pulmonary veins isolation may be effective in patients with chronic
      AF, and whether there is a role for mapping guided minimal invasive surgical
      treatment of AF in the near future.

PMID- 17031418
TI  - Korean American Men's Perceptions about Smoking-Related Symptomatology:
      Implications for Intervention.
AB  - This study examines what midlife and older (age 45 to 74) Korean American men who
      are current or former cigarette smokers think cause symptoms or health problems
      that may be related to smoking cigarettes. The study also examines how those
      perceptions influence attitudes and behaviors regarding smoking cessation.
      Separate focus groups were conducted with seven current smokers and nine former
      smokers in the Korean language in a Korean American. Current smokers experienced
      few symptoms or health problems that they attribute to smoking, and they
      generally do not regard smoking as a cause of symptoms or health problems. Former
      smokers generally quit smoking in response to experiencing a wide range of
      symptoms or health problems that they attribute to smoking or that they believe
      smoking exacerbates. A pervasive theme among both groups is that health is a
      function of a person's physical constitution. The perception is that those born
      with a strong or special physical constitution are able to smoke and be healthy;
      persons with a weak physical constitution or who are predisposed to be ill should
      not smoke or should quit smoking. Smoking-cessation interventions for midlife and
      older Korean American men should take these findings into account.

PMID- 17031419
TI  - Gastric Cancer in Korean Americans: Risks and Reductions.
AB  - Gastric cancer is one of the leadings cause of cancer worldwide. However, Koreans
      have the highest reported incidence of this deadly disease. Risk factors
      predisposing to the formation of gastric cancer include a combination of
      environmental risks, such as diet and infection (Helicobacter pylori), and, in
      some cases, genetic predisposition. Early screening and detection is essential to
      reduce gastric cancer mortality. The low prevalence and late onset of gastric
      cancer in Americans, compared to Korean Americans, however, has hindered our
      ability to risk stratify, screen, and improve early detection in Korean
      Americans, thereby contributing to the increasing mortality in this group.
      Gastric cancer control must focus on improved medical technology, in combination
      with community outreach, education, and awareness. Korean community services,
      church-based groups, media campaigns, medical communities, both academic and
      community based, and industry collaborations are essential to heighten awareness
      about gastric cancer in Korean Americans. Efforts to reduce the burden of gastric
      cancer in Korean Americans must focus on the dissemination of information to
      those most affected by the disease and those serving this community.

PMID- 17031420
TI  - Cultural Perspectives on Korean American Cancer Control.
AB  - This paper emphasizes the importance of sociocultural research for successful
      ethnic-based cancer control. The article first delineates some demographic
      characteristics of Korean Americans and then describes six subcultural groups
      within this population, illuminating that Korean Americans are a diverse people.
      The author emphasizes that any cancer control program needs to acknowledge these
      cultural differences in selecting the target population, identifying intervention
      strategies, and training a team of health-care professionals, as well as in
      determining psychological factors related to cancer. The author also suggests
      that the traditional Korean American notion of health, the preventive approach to
      illness by using food as medicine, the traditional classification of body types,
      and the sasang theory for the treatment of illness are all important factors
      worthy of further research. Finally, the synchronistic and holistic approach to
      health common among Korean Americans is described by citing recent studies of
      cancer control that combine the use of Western medicine together with proper
      physical exercise, diet control, and psychological and family counseling.

PMID- 17031421
TI  - Magnetic assisted navigation in electrophysiology and cardiac resynchronisation:
      a review.
AB  - Magnetic assisted navigation is a new innovation that may prove useful in
      catheter ablation of cardiac arrhythmias and cardiac resynchronization therapy.
      The ability to steer extremely floppy catheters and guidewires may allow for
      these to be positioned safely in previously inaccessible areas of the heart. The
      integration of other new technology, such as image integration and
      electroanatomic mapping systems, should advance our abilities further. Although
      studies have shown the technology to be feasible, with the advantage to the
      physician of decreased radiation exposure, studies need to be performed to show
      additional benefit over standard techniques.

PMID- 17031422
TI  - Synthesis, surface functionalization, and properties of freestanding silicon
      nanocrystals.
AB  - Freestanding silicon nanoparticles (FS-nc-Si) have intriguing chemical and
      optical properties. The present contribution outlines known synthetic
      methodologies and protocols for surface functionalization. Recent advancements in
      tailoring the photoluminescence properties of FS-nc-Si and future research
      directions will be briefly discussed.

PMID- 17031423
TI  - Crystal engineering of coordination polymers using 4,4'-bipyridine as a bond
      between transition metal atoms.
AB  - Coordination polymers have attracted an enormous interest among chemists due to
      their novel physical and chemical properties. This review describes the role of
      4,4'-bipyridine in discovering various coordination polymers with novel
      topologies that range from one-dimensional to three dimensional. The geometries
      of coordination polymers of bipy include linear, zigzag, four-fold helices,
      molecular antenna, ladder, railroad, double, triple and quadruple chains,
      bilayer, square and rectangular grid, honeycomb layers, Lincoln Logs, 3D frames,
      diamondoid, 4(2) x 8(2) and cubic networks.

PMID- 17031424
TI  - Supported cobalt mediated radical polymerization (SCMRP) of vinyl acetate and
      recycling of the cobalt complex.
AB  - Cobalt complexes supported on silica and Merrifield resin are effective mediators
      for the controlled radical polymerization of vinyl acetate.

PMID- 17031425
TI  - Gold nanocomposites with rigid fully conjugated heteroditopic ligands shell as
      nanobuilding blocks for coordination chemistry.
AB  - Monodisperse and solvent adaptable gold nanoparticles stabilized by rigid and
      fully conjugated modified neocuproinium and terpyridinium salts have been
      characterized and further used as nanobuilding blocks for the synthesis of gold
      nanoparticles functionalized by polypyridyl ruthenium complexes.

PMID- 17031426
TI  - Synthesis of the DEF-bis-spiroacetal of spirastrellolide A exploiting a double
      asymmetric dihydroxylation/spiroacetalisation strategy.
AB  - An efficient synthesis of the C(26)-C(40) tricyclic [5,6,6]-bis-spiroacetal
      segment of the marine macrolide spirastrellolide A has been developed, exploiting
      a novel double Sharpless asymmetric dihydroxylation/spiroacetalisation sequence.

PMID- 17031427
TI  - The reductive amination of aldehydes and ketones by catalytic use of
      dibutylchlorotin hydride complex.
AB  - The reductive amination of aldehydes or ketones using Ph(2)SiH(2) or PhSiH(3) has
      been effectively promoted by the direct use of Bu(2)SnClH-pyridine N-oxide as a
      catalyst; this method has advantages in terms of its mild conditions and wide
      application to various carbonyls and amines, including aliphatic examples.

PMID- 17031428
TI  - New palladium catalysed reactions of bromoporphyrins: synthesis and crystal
      structures of nickel(ii) complexes of primary 5-aminoporphyrin, 5,5'
      bis(porphyrinyl) secondary amine, and 5-hydroxyporphyrin.
AB  - Primary aminoporphyrin, secondary bis(porphyrinyl)amine and hydroxyporphyrin
      complexes have been isolated and characterised both spectroscopically and
      crystallographically from the reaction of 5-bromo-10,15,20
      triphenylporphyrinatonickel(ii) with hydrazine under palladium catalysis.

PMID- 17031429
TI  - The photoinduced long-lived charge-separated state of Ru(bpy)3-methylviologen
      with cucurbit[8]uril in aqueous solution.
AB  - A stable 1 : 1 inclusion complex of Ru(bpy)(3)-MV(2+) with cucurbit[8]uril
      (CB[8]) is formed in aqueous solution; upon light irradiation, a long lived (tau
      approximately 2 micros) charge-separated state Ru(3+)-MV(+ )-CB[8] is observed.

PMID- 17031430
TI  - Facile in situ preparation of biologically active multivalent glyconanoparticles.
AB  - Biologically active multivalent glyconanoparticles are prepared in an extremely
      simple method by reduction of well-defined glycopolymers, prepared by RAFT
      polymerisation, in an aqueous solution of HAuCl(4).

PMID- 17031431
TI  - A high-throughput screening assay for hydroxynitrile lyase activity.
AB  - A high-throughput screening assay for hydroxynitrile lyase activity accepting a
      wide range of HNL-substrates is presented, which is useful either for enzyme
      fingerprinting or screening of huge variant libraries generated in metagenome or
      directed evolution approaches.

PMID- 17031432
TI  - The isolable matryoshka nesting doll icosahedral cluster [As@Ni12@As20]3- as a
      "superatom": analogy with the jellium cluster Al13- generated in the gas phase by
      laser vaporization.
AB  - The valence electrons in the recently reported icosahedral cluster
      [As@Ni(12)@As(20)](3-) with a Russian matryoshka nesting doll structure can be
      partitioned so that the central As atom has the rare gas configuration, as As(3
      ), and the intermediate Ni(12) icosahedron receives 40 electrons from the lone
      pairs of the outer As(20) dodecahedron to be isoelectronic with the Al(13)(-)
      jellium cluster found in molecular beam experiments.

PMID- 17031433
TI  - Dynamic ligation at the first amine-coordinated iron hydrogenase active site
      mimic.
AB  - The first model of the iron hydrogenase active site has been prepared in which an
      amine ligand is loosely coordinated to an Fe(i) centre, and can be replaced by a
      solvent molecule; irrespective of the ligand set, the one electron reduction of
      both complexes is chemically reversible and is shown to proceed through the same
      species which features a bridging CO ligand.

PMID- 17031434
TI  - Total synthesis of antillatoxin.
AB  - The total synthesis of natural (4R,5R)-antillatoxin and its analog (4S,5S)
      antillatoxin has been achieved; the optically pure key intermediates were
      prepared from indium mediated allylation of either primary or secondary allylic
      bromide with aldehyde in aquoues media, followed by highly selective Luche's
      reduction and chiral resolution.

PMID- 17031435
TI  - Competitive photoinduced electron transfer by the complex formation of porphyrin
      with cyclodextrin bearing viologen.
AB  - Photoinduced electron transfer between a porphyrin and a new guest cyclodextrin
      bearing viologen occurs by a supramolecular formation with conformational change
      of a guest molecule.

PMID- 17031436
TI  - Solution structures of thiopeptide antibiotics.
AB  - A detailed NMR study of the thiopeptide amythiamicin D establishes its solution
      conformation and the presence of a single intramolecular hydrogen bond involving
      NH13 and O28, and also provides the first evidence for self-association of
      thiopeptides in solution.

PMID- 17031437
TI  - Solution state coordination polymers featuring wormlike macroscopic structures
      and cage-polymer interconversions.
AB  - In the absence of coordinating solvents and anions, silver salts and
      triphosphines form viscous, thixotropic coordination polymers in solution, which
      aggregate into unusual wormlike macroscopic structures and undergo cage-polymer
      interconversions depending on the stoichiometry and presence of templating
      anions.

PMID- 17031438
TI  - Self-aggregated perfluoroalkylated hexa-peri-hexabenzocoronene fibers observed by
      cryo-SEM and fluorescence spectroscopy.
AB  - The self-assembled architectures in solution of a new HBC derivative bearing
      perfluoroalkylated side chains were investigated by optical excitation and
      emission spectroscopy and correlated to cryo-SEM, a new technique in organic
      chemistry.

PMID- 17031439
TI  - Selective detection of cesium by a water-soluble fluorescent molecular sensor
      based on a calix[4]arene-bis(crown-6-ether).
AB  - A tetrasulfonated calixarene with two appended crowns, each including a
      dioxycoumarin fluorophore, is highly soluble in water and shows excellent
      selectivity for cesium ions.

PMID- 17031440
TI  - Novel immobilization method of enzymes using a hydrophilic polymer support.
AB  - A novel immobilization of an enzyme with a hydrophilic polymer support in organic
      solvents has been developed utilizing the "polymer-incarcerated (PI) method",
      which has been used to immobilize metal catalysts; the kinetic resolution of
      secondary alcohols was found to proceed more smoothly using immobilized lipases
      (CALB) than free lipases.

PMID- 17031441
TI  - A short water-soluble self-assembling peptide forms amyloid-like fibrils.
AB  - A water-soluble tripeptide Val-Ile-Ala (VIA) , bearing sequence identity with the
      C-terminal portion of the Alzheimer Abeta-peptide (Abeta(40-42)), self-assembles,
      in crystalline form, to produce an intermolecularly hydrogen bonded
      supramolecular beta-sheet structure which self-associates to form straight,
      unbranched nanofibrils exhibiting amyloid-like behavior; in contrast, the
      synthetic tripeptide Ala-Val-Ile (AVI) self-assembles to produce a beta-sheet
      structure that forms branched nanofibrils which do not show any characteristic
      features of amyloid-like fibrils.

PMID- 17031442
TI  - Gas-phase regiocontrolled generation of charged amino acid and peptide radicals.
AB  - The combined use of advanced mass spectrometry experiments, condensed-phase
      synthesis of serine and homoserine nitrate ester radical precursors, and high
      level ab initio calculations provides a powerful way of examining the fundamental
      reactivity of radicals derived from peptides.

PMID- 17031443
TI  - Efficient visible light-active N-doped TiO2 photocatalysts by a reproducible and
      controllable synthetic route.
AB  - A reproducible and controllable method allows the synthesis of practical
      quantities of efficient, visible light active TiO(2)(N) photocatalysts in which
      the nitrogen content may be varied to achieve optimum performance.

PMID- 17031444
TI  - Annulation of beta-aryl-alpha-nitro-alpha,beta-enals and 2,2-dimethyl-1,3-dioxan
      5-one: a one-step assembly of nitrocyclitols. Application to a short practical
      synthesis of (+/-)-7-deoxy-2-epi-pancratistatin tetraacetate.
AB  - A novel, highly stereocontrolled formal [3 + 3] annulation of beta-aryl-alpha
      nitro-alpha,beta-enals with the enamine derived from 2,2-dimethyl-1,3-dioxan-5
      one and pyrrolidine afforded protected nitrocyclitols with five newly created
      stereocentres and constituted the key step in a short, gram-scale synthesis of a
      pancratistatin analogue.

PMID- 17031445
TI  - An enantioselective fluorescence sensing assay for quantitative analysis of
      chiral carboxylic acids and amino acid derivatives.
AB  - A chiral 1,8-diacridylnaphthalene-derived fluorosensor exhibiting a C(2)
      symmetric cleft designed for stereoselective interactions with hydrogen bond
      donors has been used for the determination of both concentration and enantiomeric
      composition of carboxylic acids and amino acid derivatives.

PMID- 17031446
TI  - Highly-oxidised, sulfur-rich, mixed-valence vanadium(IV/V) complexes.
AB  - The reactions of [V(2)(micro-S(2))(2)(S(2)CNR(2))(4)] (R = alkyl) with NOBF(4)
      produce highly-oxidised, sulfur-rich, V(iv/v) complexes, [V(2)(micro
      S(2))(2)(S(2)CNR(2))(4)]BF(4), that exhibit 15-line EPR spectra and structures
      consistent with Class III mixed-valence behaviour.

PMID- 17031447
TI  - High rates of psychiatric co-morbidity in PDD-NOS.
AB  - Rates of co-morbid psychiatric conditions in children with Pervasive
      Developmental Disorder-Not Otherwise Specified (PDD-NOS) are hardly available,
      although these conditions are often considered as more responsive to treatment
      than the core symptoms of PDD-NOS. Ninety-four children with PDD-NOS, aged 6-12
      years were included. The DISC-IV-P was administered. At least one co-morbid
      psychiatric disorder was present in 80.9% of the children; 61.7% had a co-morbid
      disruptive behavior disorder, and 55.3% fulfilled criteria of an anxiety
      disorder. Compared to those without co-morbid psychiatric disorders, children
      with a co-morbid disorder had more deficits in social communication. Co-morbid
      disorders occur very frequently in children with PDD-NOS, and therefore clinical
      assessment in those children should include assessment of co-morbid DSM-IV
      disorders.

PMID- 17031448
TI  - Memory illusion in high-functioning autism and Asperger's disorder.
AB  - In this study, 13 individuals with high-functioning autism (HFA), 15 individuals
      with Asperger's disorder (AD), and age-, and IQ-matched controls were presented a
      list of sentences auditorily. Participants then evaluated semantically related
      but new sentences and reported whether they were old or new. The total rates of
      false recognition for semantically related sentences were similar among the three
      groups. Nevertheless, memory illusion on some aspects was reduced in HFA
      participants. These results suggest that HFA have difficulties in semantic
      association. Although individuals with AD showed no quantitative abnormalities of
      memory illusion, some contributing factors were atypical. These findings are
      discussed in terms of schema theory, enhanced perceptual processing hypothesis,
      and weak central coherence hypothesis.

PMID- 17031449
TI  - Autism spectrum phenotype in males and females with fragile X full mutation and
      premutation.
AB  - The behavioural phenotype of autism was assessed in individuals with full
      mutation and premutation fragile X syndrome (FXS) using the Autism Diagnostic
      Observation Scale-Generic (ADOS-G) and the Autism Diagnostic Interview (ADI-R).
      The participants, aged 5-80 years, comprised 33 males and 31 females with full
      mutation, 7 males and 43 females with premutation, and 38 non-fragile X relatives
      (29 males, 9 females). In the full mutation group, a total of 67% males and 23%
      females met either the Autism Disorder (AD) or the Autism Spectrum Disorder (ASD)
      criteria on at least one of the diagnostic tests. In the premutation group, 14%
      males and 5% females met the ADOS-G criteria for ASD. The presence of autism
      manifestations in males and females with full mutation and premutation provide
      support for a spectrum view.

PMID- 17031450
TI  - Assessing the early characteristics of autistic disorder using video analysis.
AB  - The behaviours of infants were observed using home videos, in an attempt to
      identify social difficulties characteristic of infants with autistic disorder.
      Three groups of infants were analysed: 15 infants who had later been diagnosed
      with autism, 15 infants who had a developmental or language delay, and 15
      typically developing infants. Social behaviours were coded using both
      quantitative and qualitative measures. The principal discriminating items between
      the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory
      postures', and 'proto-declarative showing'. The results suggest that these
      children later diagnosed with autism are clinically distinct from their peers
      before the age of two years, and that there are clearly observable behaviours
      which are important predictors of autistic disorder in pre-verbal children.

PMID- 17031451
TI  - Accuracy of dual-source CT coronary angiography: First experience in a high pre
      test probability population without heart rate control.
AB  - The aim of this study was to assess the diagnostic accuracy of dual-source
      computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a
      population with extensive coronary calcifications without heart rate control.
      Thirty patients (24 male, 6 female, mean age 63.1+/-11.3 years) with a high pre
      test probability of CAD underwent DSCT coronary angiography and invasive coronary
      angiography (ICA) within 14+/-9 days. No beta-blockers were administered prior to
      the scan. Two readers independently assessed image quality of all coronary
      segments with a diameter > or =1.5 mm using a four-point score (1: excellent to
      4: not assessable) and qualitatively assessed significant stenoses as narrowing
      of the luminal diameter >50%. Causes of false-positive (FP) and false-negative
      (FN) ratings were assigned to calcifications or motion artifacts. ICA was
      considered the standard of reference. Mean body mass index was 28.3+/-3.9 kg/m2
      (range 22.4-36.3 kg/m2), mean heart rate during CT was 70.3+/-14.2 bpm (range 47
      102 bpm), and mean Agatston score was 821+/-904 (range 0-3,110). Image quality
      was diagnostic (scores 1-3) in 98.6% (414/420) of segments (mean image quality
      score 1.68+/-0.75); six segments in three patients were considered not assessable
      (1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe
      calcifications accounted for false ratings in nine segments (eight FP/one FN) and
      motion artifacts in two segments (one FP/one FN). Overall sensitivity,
      specificity, positive and negative predictive value for evaluating CAD were 96.4,
      97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT
      coronary angiography provides high diagnostic accuracy for assessment of CAD in a
      high pre-test probability population with extensive coronary calcifications and
      without heart rate control.

PMID- 17031452
TI  - Teleradiology applications with DICOM-e-mail.
AB  - For the connection of several partners to a Dicom-e-mail based teleradiology
      network concepts were developed to allow the integration of different
      teleradiology applications. The organisational and technical needs for such an
      integration were analysed. More than 60 institutions including 23 hospitals in
      the Rhein-Neckar-Region, Germany were connected. The needed functionality was
      grouped in six teleradiology applications (emergency consultation, tele-guided
      examinations, expert consultations, cooperative work, scientific cooperations and
      homework with on call services) and their technical and organisational needs
      according to availability, speed of transfer, workflow definitions and data
      security needs was analysed. For the local integration of teleradiology services
      the setup and workflow is presented for a standalone teleradiology workstation
      and a server based teleradiology gateway. The line type needed for different
      groups of applications and users is defined. The security concept and fallback
      strategies are laid out, potential security problems and sources of errors are
      discussed. The specialties for the emergency teleradiology application are
      presented. The DICOM-e-mail protocol is a flexible and powerful protocol that can
      be used for a variety of teleradiology applications. It can meet the conditions
      for emergency applications but is limited if synchronous applications like
      teleconferences are needed.

PMID- 17031453
TI  - Cost effectiveness of coronary angiography and calcium scoring using CT and
      stress MRI for diagnosis of coronary artery disease.
AB  - We compared the cost effectiveness of recent approaches [coronary angiography and
      calcium scoring using computed tomography (CT) and stress magnetic resonance
      imaging (MRI)] to the diagnosis of coronary artery disease (CAD) with those of
      the traditional diagnostic modalities [conventional angiography (CATH), exercise
      ECG, and stress echocardiography] using a decision tree model. For patients with
      a 10% to 50% pretest likelihood of coronary artery disease, non-invasive coronary
      angiography using CT was the most cost effective approach, with costs per
      correctly identified CAD patient of euro4,435 (10% likelihood) to euro1,469 (50%
      likelihood). Only for a pretest likelihood of 30% to 40% was calcium scoring
      using CT more cost effective than any of the traditional diagnostic modalities,
      while MRI was not cost effective for any pretest likelihood. At a pretest
      likelihood of 60%, CT coronary angiography and CATH were equally effective, while
      CATH was most cost effective for a pretest likelihood of at least 70%. In
      conclusion, up to a pretest likelihood for coronary artery disease of 50%, CT
      coronary angiography is the most cost-effective procedure, being superior to the
      other new modalities and the most commonly used traditional diagnostic
      modalities. With a very high likelihood for disease (above 60%), CATH is the most
      effective procedure from the perspective of society.

PMID- 17031454
TI  - MR-compatible assistance system for punction in a high-field system: device and
      feasibility of transgluteal biopsies of the prostate gland.
AB  - We present the first cadavic study results concerning the feasibility of the use
      of an MR-guided assistance system, Innomotion (Innomedic, Herxheim, Germany), for
      accurate and consistent placement of percutaneous needles in the prostate gland.
      The MR-compatible assistance system consists of a C-arch, guiding arm and
      application module (AMO). T1-weighted fast low angle shot (FLASH) 2-D-GRE
      sequence (TR/TE=110/4 ms) and T2-weighted turbo spin-echo (TSE)-sequences
      (TR/TE=3200/97 ms) in transversal orientation were used for the monitoring of the
      punction of the prostate gland. Planning and control of the intervention is to be
      made outside the scanner room on a desktop computer that receives DICOM images
      from the scanner. Servopneumatic drives move the AMO to the insertion point. The
      physician has to introduce the punction needle manually. The mean deviation of
      the needle tip to the target in a gel phantom was 0.35 mm. An accurate punction
      of the prostate gland can easily be performed using this system with a
      transgluteal access. The T2-weighted images are superior for the evaluation of
      the prostate anatomy and the needle position during the interventions. In
      conclusion, our preliminary results indicate that this MR-guided assistance
      system is suitable for an accurate transgluteal needle placement in the prostate.

PMID- 17031455
TI  - [Laparoscopy for abdominal trauma].
AB  - With increasing experience in minimally invasive surgery, laparoscopy's role in
      abdominal trauma can be defined exactly. Main exclusion criteria are hemodynamic
      instability and increased intracranial pressure. A literature review of 1996 to
      2006 reveals perforating injury mainly of the left thoracoadominal area as the
      most important indication for laparoscopy . Its goal is to determine
      intraperitoneal lesions and integrity of the abdominal wall and diaphragm. Minor
      injuries of the parenchymatous organs and diaphragm can be successfully repaired
      laparoscopically. In blunt abdominal trauma, laparoscopy is used as a
      complementary diagnostic device in case ultrasound and multislice CT show unclear
      findings and the patient's clinical status requires invasive measures. The clear
      weakness of laparoscopy in abdominal trauma is its inability to identify reliably
      hollow viscus perforation and retroperitoneal injury. In this, sensitivity is
      only 25%. In case of proven lesions of the gastrointestinal tract, conversion to
      laparotomy is to be considered. Despite the reports on laparoscopic treatment,
      open repair of hollow organ injuries is still to be recommended.

PMID- 17031456
TI  - Dynamic model of the process of protein synthesis in eukaryotic cells.
AB  - Protein synthesis is the final step of gene expression in all cells. In order to
      understand the regulation of this process, it is important to have an accurate
      model that incorporates the regulatory steps. The model presented in this paper
      is composed of set of differential equations which describe the dynamics of the
      initiation process and its control, as well as peptide elongation, starting with
      the amino acids available for peptide creation. A novel approach for modeling the
      elongation process permits useful prediction of protein production and
      consumption of energy and amino acids, as well as ribosome loading rate and
      ribosome spacing on the mRNA.

PMID- 17031457
TI  - Evidence for an early gene duplication event in the evolution of the
      mitochondrial transcription factor B family and maintenance of rRNA
      methyltransferase activity in human mtTFB1 and mtTFB2.
AB  - Most metazoans have two nuclear genes encoding orthologues of the well
      characterized Saccharomyces cerevisiae mitochondrial transcription factor B (sc
      mtTFB). This class of transcription factors is homologous to the bacterial KsgA
      family of rRNA methyltransferases, which in Escherichia coli dimethylates
      adjacent adenine residues in a stem-loop of the 16S rRNA. This
      posttranscriptional modification is conserved in most metazoan cytoplasmic and
      mitochondrial rRNAs. Homo sapiens mitochondrial transcription factor B1 (h
      mtTFB1) possesses this enzymatic activity, implicating it as a dual-function
      protein involved in mitochondrial transcription and translation. Here we
      demonstrate that h-mtTFB2 also has rRNA methyltransferase activity but is a less
      efficient enzyme than h-mtTFB1. In contrast, sc-mtTFB has no detectable rRNA
      methyltransferase activity, correlating with the lack of the corresponding
      modification in the mitochondrial rRNA of budding yeast. Based on these results,
      and reports that Drosophila melanogaster mtTFB1 and mtTFB2 do not have completely
      overlapping functions, we propose a model for human mtDNA regulation that takes
      into account h-mtTFB1 and h-mtTFB2 likely having partially redundant
      transcription factor and rRNA methyltransferase functions. Finally, phylogenetic
      analyses of this family of proteins strongly suggest that the presence of two
      mtTFB homologues in metazoans is the result of a gene duplication event that
      occurred early in eukaryotic evolution prior to the divergence of fungi and
      metazoans. This model suggests that, after the gene duplication event,
      differential selective pressures on the rRNA methyltransferase and transcription
      factor activities of mtTFB genes occurred, with extreme cases culminating in the
      loss of one of the paralogous genes in certain species.

PMID- 17031459
TI  - Nonrandom representation of sex-biased genes on chicken Z chromosome.
AB  - Several lines of evidence suggest that the X chromosome of various animal species
      has an unusual complement of genes with sex-biased or sex-specific expression.
      However, the study of the X chromosome gene content in different organisms
      provided conflicting results. The most striking contrast concerns the male-biased
      genes, which were reported to be almost depleted from the X chromosome in
      Drosophila but overrepresented on the X chromosome in mammals. To elucidate the
      reason for these discrepancies, we analysed the gene content of the Z chromosome
      in chicken. Our analysis of the publicly available expressed sequence tags (EST)
      data and genome draft sequence revealed a significant underrepresentation of
      ovary-specific genes on the chicken Z chromosome. For the brain-expressed genes,
      we found a significant enrichment of male-biased genes but an indication of
      underrepresentation of female-biased genes on the Z chromosome. This is the first
      report on the nonrandom gene content in a homogametic sex chromosome of a species
      with heterogametic female individuals. Further comparison of gene contents of the
      independently evolved X and Z sex chromosomes may offer new insight into the
      evolutionary processes leading to the nonrandom genomic distribution of sex
      biased and sex-specific genes.

PMID- 17031458
TI  - Ancient phylogenetic beginnings of immunoglobulin hypermutation.
AB  - Many structures and molecules closely related to those involved in the specific
      process of immunoglobulin (Ig) hypermutation existed before the appearance of
      primordial Ig genes. Consequently, these structures can be found even in animals
      and organisms distinct from vertebrates; likewise, homologues of hypermutation
      enzymes are present in a broad range of species, from bacteria to mammals. Our
      analysis, based predominantly on primary structure, demonstrates the existence of
      molecules similar to Ig domains, variable Ig domains (IGv), and antigen receptors
      (AR) in unicellular organisms, nonvertebrate metazoans, and nonvertebrate
      Coelomata, respectively. In addition, we deal here with some important structural
      properties of CDR1-like segments of the selected sponge adhesion molecule GCSAMS
      exhibiting chimerical Ig domain similarities, and demonstrate the occurrence of
      conserved regions corresponding to Ohno's modern intact primordial building block
      in the C-terminal part of IGv-related segments of nonvertebrate origin. The
      results of our analysis are also discussed with respect to the possible phylogeny
      of molecules preceding the hypothetical common antigen receptor ancestor.

PMID- 17031460
TI  - Domain-specific positive selection contributes to the evolution of Arabidopsis
      leucine-rich repeat receptor-like kinase (LRR RLK) genes.
AB  - Leucine-rich repeat receptor-like kinases (LRR RLKs) comprise the largest group
      within the plant receptor-like kinase (RLK) superfamily, and the Arabidopsis
      genome alone contains over 200 LRR RLK genes. Although there is clear evidence
      for diverse roles played by individual LRR RLK genes in Arabidopsis growth and
      development, the evolutionary mechanism for this functional diversification is
      currently unclear. In this study, we focused on the LRRII RLK subfamily to
      investigate the molecular mechanisms that might have led to the functional
      differentiation of Arabidopsis LRR RLK genes. Phylogenetic analysis of 14 genes
      in this subfamily revealed three well-supported groups (I, II, and III). RT-PCR
      analysis did not find many qualitative differences in expression among these 14
      genes in various Arabidopsis tissues, suggesting that evolution of regulatory
      sequences did not play a major role in their functional divergence. We analyzed
      substitution patterns in the predicted ligand-binding regions of these genes to
      examine if positive selection has acted to produce novel ligand-binding
      specificities, using the nonsynonymous/synonymous rate ratio (d (N)/d (S)) as an
      indicator of selective pressure. Estimates of d (N)/d (S) ratios from multiple
      methods indicate that nonsynonymous substitutions accumulated during divergence
      of the three lineages. Positive selection is likely to have occurred along the
      lineages ancestral to groups II and III. We suggest that positive selection on
      the ligand-binding sites of LRRII RLKs promoted diversification of ligand-binding
      specificities and thus contributed to the functional differentiation of
      Arabidopsis LRRII RLK genes during evolution.

PMID- 17031461
TI  - Tandem repetitive D domains of the sperm ligand zonadhesin evolve faster in the
      paralogue than in the orthologue comparison.
AB  - Gene duplication is regarded as an important evolutionary mechanism creating
      genetic and phenotypic novelty. At the same time, the evolutionary mechanisms
      following gene duplication have been a subject of much debate. Here we analyze
      the sequence evolution of zonadhesin, a mammalian sperm ligand that binds to the
      oocyte zona pellucida in a species-specific manner. In pig, rabbit, and primates,
      precursor zonadhesin comprises, among others, one partial and four complete
      tandem repetitive D domains. The mouse precursor is distinguished by 20
      additional partial D3 domains consisting of 120 amino acids each. This gene
      structure allows sequence comparison in both paralogues and orthologues. Detailed
      sequence analysis reveals that D domains evolve faster across paralogues than
      orthologues. Moreover, at the codon level, partial D3 paralogues of mouse show
      evidence of positive selection, whereas the corresponding orthologues do not.
      Individual posttranslational motif patterns and positive selection point to
      neofunctionalization of partial D3 paralogues of mouse, rather than
      subfunctionalization. However, as we found additional evidence for homogenization
      by partial gene conversion, sequence evolution of partial D3 paralogues of mouse
      might be better described as a combination of divergent and convergent evolution.
      So far, the divergence at the codon level has outbalanced the convergence at the
      level of smaller fragments. The probable driving force behind the evolutionary
      patterns observed is sexual selection. We finally discuss whether the functional
      determination influences the evolutionary regime acting on sperm ligands and egg
      receptors, respectively.

PMID- 17031462
TI  - Experimental characterization of vibrated granular rings.
AB  - We report an experimental study of the statistical properties of vibrated
      granular rings. In this system, a linked rod and bead metallic chain in the form
      of a ring is collisionally excited by a vertically oscillating plate. The
      dynamics are driven primarily by inelastic bead-plate collisions and are
      simultaneously constrained by the rings' physical connectedness. By imaging many
      instances of the ring configurations, we measure the ensemble averages and
      distributions of several physical characteristics on the scale of individual
      beads and composite ring. We study local properties such as inter-bead separation
      and inter-bonds angles, and global properties such as the radius of gyration and
      center-of-mass motion. We characterize scaling with respect to the size of the
      chain.

PMID- 17031463
TI  - The effect of packed red blood cell storage on arachidonic acid and advanced
      glycation end-product formation.
AB  - INTRODUCTION: The transfusion of packed red blood cells (PRBCs) is a significant
      risk to blood recipients. Blood banking procedures permit the storage of PRBCs
      for up to 42 days. Storage of PRBCs can cause polymorphonuclear granulocytes
      (PMNs) activation and the development of neutrophil-mediated transfusion-related
      acute lung injury. The aim of our study was to determine if PRBC storage has an
      influence on the formation of arachidonic acid (AA) and advanced glycation end
      products (AGEs). MATERIALS AND METHODS: Twenty units of PRBCs were used to
      measure AA and AGE levels. The samples were taken on the 0th, 14th, 28th, and
      42nd days of PRBC storage. The AA level was analyzed by gas-liquid chromatography
      mass spectrometry and AGE level by an immunoenzymatic test. RESULTS: During the
      first 14 days of PRBC storage, the AA level significantly increased and then
      slowly decreased. The AGE level increased continuously during the whole time of
      the study. In a model experiment, the AA glycoxidation product trans-2-nonenal
      (T2N) formed adducts in reaction with hemoglobin which were detectable with the
      test for AGE. CONCLUSIONS: It is highly probable that the observed increase in
      AGE level is related to the decrease in AA in PRBCs, which can be associated with
      the formation of toxic aldehydes, especially T2N and 4-hydroxynonenal (HNE), from
      AA. Glucose in the PRBCs (preservative solution) can contribute to AGE formation
      as well. The formation of AGEs, HNE, and T2N in PRBCs, their influence on PMNs in
      vitro, and confirmation of our assumption need further studies.

PMID- 17031464
TI  - All roads lead to Rome: pathways of NKT cells promoting asthma.
AB  - NKT cells are the prominent manipulator in asthma development. Asthmatic NKT
      cells migrate from thymus, spleen, liver and bone marrow into blood vessels, and
      then concentrate in airway bronchi mucosa. This recruitment is dependent on high
      expression of CCR9 and engagement of CCL25/CCR9. NKT cells promote asthma in two
      different pathways. One is an indirect pathway. NKT cells contact with CD3(+) T
      cells and induce them secreting large quantity of Th2 cytokines (IL-4, IL-13),
      which requires the participation of dentritic cells and the synergic signaling of
      CCL25/CCR9 and CD226. The other is a direct pathway. Circulating asthmatic NKT
      cells selectively highly express Th1 cytokines (IFN-gamma). Once reached airway
      epithelium, most NKT cells shift to Th2-bias, highly expressing IL-4, IL-13, but
      not IFN-gamma. Both pathways lead to airway hyperresponsiveness and inflammation,
      asthma development. Comparing to the well documented suppressive regulatory T
      cells, CD4(+)CD25(+) T cells, NKT cells perform as a novel active regulator in
      asthma. These recent understanding of NKT cells performance in the development of
      asthma might unveil new therapy targets and management strategies for asthma.

PMID- 17031465
TI  - Increased whole blood chemiluminescence in patients with chronic renal failure
      independent of hemodialysis treatment.
AB  - INTRODUCTION: The luminol-enhanced whole blood chemiluminescence (LBCL) assay is
      a rapid assay for the measurement of reactive oxygen species (ROS) generation by
      circulating phagocytes. This study's aim was to determine if patients on
      maintenance hemodialysis (HD) and non-dialyzed patients with chronic renal
      failure (CRF) have altered LBCL and if dialysis itself affects ROS production in
      the blood. MATERIALS AND METHODS: Twenty-six HD patients, 11 non-dialyzed
      patients with CRF, and 20 gender- and age-matched healthy controls were studied.
      Resting (rCl) and 2 x 10(-5) M n-formyl-methionyl-leucyl-phenylalanine-stimulated
      LBCL (peak chemiluminescence: pCl, total light emission after agonist addition:
      tCl) calculated per 10(4) phagocytes present in the 3-mul blood samples were
      measured with a Bio-Orbit 1251 luminometer at 37 degrees C for 11 min. RESULTS:
      Prior to the HD session, median rCL, pCL, and tCL were 1.5, 3.0, and 2.8 times
      higher in HD patients than in healthy controls (p<0.01) and tended to increase at
      the end of the session. Significant increases in tCl were observed at 30 min and
      240 min (end) of HD (1023.5 vs. 1810.6 vs. 2006.8 arbitrary units x s/10(4)
      phagocytes, n=9, p<0.05). Median pCl and tCl were 5.0 and 4.3 times higher in non
      dialyzed patients with CRF than in healthy controls (p<0.001). However, no
      significant differences were found between pre- and post-HD LBCL of HD patients
      and the LBCL of non-dialyzed patients with renal failure. CONCLUSIONS: Blood from
      patients with renal failure generates elevated amounts of oxidants independently
      of HD treatment. This may add to the understanding of the nature of oxidative
      stress and suggests the need of anti-oxidant treatment in these patients.

PMID- 17031466
TI  - Langerhans cells in vulvar lichen sclerosus and vulvar squamous cell carcinoma.
AB  - INTRODUCTION: Langerhans cells (LCs), specializing in antigen presentation, are a
      very important part of the skin immune system (SIS). MATERIALS AND METHODS: Skin
      biopsies from 22 women with vulvar lichen sclerosus (LS): 15 patients with early
      and 7 with the late stage of the disease, were evaluated. Five women with vulvar
      squamous cell carcinoma (SCC) were also examined. The control group consisted of
      9 women who underwent plastic surgery of the vulvar region. Immunohistochemical
      staining was performed on formalin-fixed paraffin-embedded tissues samples using
      antihuman CD1a antibody (NCL-CD1a-235, Novocastra). RESULTS: Increased numbers of
      LC stainings were present in early LS, whereas decreased numbers of these cells
      were present in late LS and in SCC compared with the control group. CONCLUSIONS:
      This study showed that dysregulation of the SIS may lead to suppression of LCs in
      the vulvar epithelium and may be one of the reasons for a higher tendency for
      carcinogenesis in the vulvar region.

PMID- 17031467
TI  - Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis
      of cytolytic effector cells.
AB  - Spontaneous tumors grow and kill the host unless therapy reduces their mass to a
      level where the immune system, it is thought, can control their growth and
      diffusion. Indeed, in many instances tumors can reappear, become resistant to
      therapy, and escape the host immune response. Many mechanisms of tumor escape
      operating in the tumor microenvironment have been proposed: 1) low or absent
      expression of molecules on tumor cells involved in tumor target cell recognition;
      2) absence of co-stimulation leading to tolerization of T cells; 3) soluble
      factors secreted by tumor cells inhibiting T cell response; and 4) regulatory T
      cells, myeloid suppressor cells, and stromal cells may impair immune-cell
      responses to tumors. Furthermore, tumors can release soluble molecules such as
      HLA-I (sHLA-I). This, in turn, reduces T cell-mediated immune response and
      induces apoptosis of cytolytic effector cells such as natural killer and CD8(+) T
      lymphocytes through the engagement of HLA-I receptors such as CD8 and/or
      activating isoforms of the inhibitory receptor superfamily. The release of
      soluble ligand for activating receptors, e.g. UL16 binding proteins and/or MHC
      class I-related proteins A and B, the natural ligands of NKG2D, may impair
      activation, effector cell-mediated recognition, and cytolysis of tumor cells.
      Furthermore, the elimination of anti-tumor effector cells may be achieved by
      induction of apoptosis consequent to triggering elicited via activating
      molecules, such as receptors responsible for natural cytotoxicity, upon their
      binding with ligands expressed on tumor cells.

PMID- 17031468
TI  - Regulation of cytokine transcription in the context of chromatin.
AB  - Understanding the transcriptional regulation of an important class of innate and
      adaptive immune system effector molecules, the cytokines, is increasingly
      important given the promise cytokine regulation holds for treating various
      autoimmune and inflammatory diseases. Studies defining the mechanisms regulating
      cytokine transcription initially focused on identifying the cis-acting elements
      and trans-acting factors that activate cytokine promoters and enhancers. In the
      past, these studies were largely completed in the absence of constraints
      instituted by cellular chromatin. Over the past decade it has become obvious that
      changes in chromatin accessibility critically control, rather than simply
      correlate with, the transcriptional activation of most genes, including
      cytokines. Hence candidate transcriptional activators are being re-evaluated for
      potency in the context of cellular chromatin. Several distinct mechanisms for
      manipulating the generally repressive context of chromatin have been identified
      for cytokine genes. Most recently, single nucleotide polymorphisms in cytokine
      transcriptional regulatory elements have been shown to play measurable roles in
      regulating cytokine levels in the context of naturally selected haplotypes.
      Overall, subtle differences in DNA sequence and nucleoprotein complex
      composition, including protein post-translational modification, come together in
      cell type-specific combinations to explain the normal variation in cytokine
      transcription throughout the human populace.

PMID- 17031470
TI  - Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T
      cells.
AB  - The immune system responds vigorously to invading pathogens (non-self, foreign),
      while remaining unresponsive (tolerant) to the body's own components and
      circulating constituents (self). This indifference to self components is a result
      of finely orchestrated events of thymic negative selection (central tolerance) of
      developing T cells that are autoaggressive combined with those operative in the
      periphery (peripheral tolerance) to control the activity of potentially
      autoreactive T cells that escaped thymic tolerance. Recently, autoimmune
      regulator expressed in the thymus has been identified as a critical mediator of
      central tolerance towards tissue-specific antigens. In the periphery, a variety
      of regulatory T cells are involved in effecting tolerance. There is immense
      interest and excitement about the newly identified subset of CD4(+)CD25(+) T
      cells. This is a unique subset of CD4(+) T cells that bear CD25 (IL-2Ralpha
      chain) on the cell surface in the naive state and express FoxP3 as a unique
      marker. These cells suppress the activity of autoreactive effector T cells
      primarily via cell-cell contact. The deficiency and/or altered function of
      CD4(+)CD25(+) T cells is associated with autoimmunity. Mice deficient in FoxP3
      (scurfy mice) bear an autoimmune phenotype, and human males with mutations in the
      corresponding gene express the phenotype of wide-spread autoimmunity, the immune
      dysregulation, polyendocrinopathy and enteropathy, and X-linked syndrome. In
      vitro expansion of antigen-specific CD4(+)CD25(+) T cells and their adoptive
      transfer into patients suffering from autoimmunity is emerging as a promising new
      therapeutic approach for these debilitating disorders.

PMID- 17031469
TI  - Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic
      leukemia cells to prednisolone and cytarabine.
AB  - INTRODUCTION: Thalidomide is a derivative of glutamic acid with anti-angiogenic,
      anti-inflammatory, immunomodulatory and anti-cancer properties that was found to
      inhibit the production of tumor necrosis factor alpha in vitro, stimulate
      reactive oxygen species production, and inhibit vascular endothelial growth
      factor receptor in acute leukemias. The purpose of this study was to determine
      the in vitro activity of thalidomide as a single agent and in combination with
      prednisolone or cytarabine in childhood acute lymphoblastic leukemia (ALL).
      MATERIALS AND METHODS: Bone marrow samples of 40 childhood ALL patients, normal
      lymphocytes of 9 healthy adults, and 3 lymphoid cell lines were evaluated for
      cytotoxicity of thalidomide (alone and in combination with prednisolone and
      cytarabine) using the MTT assay. Cell cycle analysis was performed by flow
      cytometry. RESULTS: Thalidomide as a single agent had weak antileukemic activity
      to the childhood ALL samples. However, in the presence of thalidomide the
      cytotoxicities of prednisolone and cytarabine were increased 3.3-fold (p<0.001)
      and 2.7-fold (p=0.002), respectively. Thalidomide increased apoptosis in
      lymphoblasts and modulated the cell-cycle arrest caused by prednisolone, but not
      that by cytarabine, in childhood ALL samples. CONCLUSIONS: Thalidomide increases
      in vitro the sensitivity of childhood ALL cells to prednisolone and cytarabine.

PMID- 17031471
TI  - Air in the carotid canal as a predictor of distal internal carotid artery
      laceration.
AB  - The authors describe a 25-year old patient with blunt trauma-induced bilateral,
      distal segment internal carotid artery (ICA) lacerations, resulting in a left
      sided direct carotid-cavernous sinus fistula (CCF) and presenting with massive
      oronasal bleeding. The combination of severe oronasal bleeding, with air in the
      carotid canal should alarm the treating physician to the presence of a distal
      internal carotid artery laceration.

PMID- 17031472
TI  - Concise preparation of N(alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine and its
      application in the synthesis of site-specifically lysine monomethylated peptide.
AB  - A concise preparation of N(alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine and its
      application in the synthesis of site-specifically lysine monomethylated peptide
      is described. N (alpha)-Fmoc-N(epsilon)-(Boc, methyl)-lysine is obtained, via
      consecutive reductive benzylation and reductive methylation in a one-pot
      reaction, followed by debenzylation through catalytic hydrogenolysis and Boc
      protection in another one-pot reaction. A peptide containing monomethylated
      lysine is successfully synthesized by incorporating N(alpha)-Fmoc-N(epsilon)
      (Boc, methyl)-lysine as a building block via solid-phase peptide synthesis.

PMID- 17031473
TI  - The five bromotryptophans.
AB  - The five regioisomeric bromotryptophans (BrTrps) play an important role in the
      life of sponges and lower marine invertebrates. These bromo-amino acids, which
      are formed by post-translational modifications, are not found in nature in their
      free state, but rather are involved in more complex structures. Any of the BrTrps
      can be part of a peptide, a cyclic peptide, an indole alkaloid, an ergot
      alkaloid, a macrocycle and others. The present review covers the synthesis,
      physical and spectroscopic properties of the five BrTrps. It also describes the
      many exiting pharmacological and biological activities played by the BrTrps and
      by various secondary metabolites containing brominated tryptophan moieties. Of
      special interest are cyclic peptides containing the 2-BrTrp unit, which were
      isolated from marine sponges e.g. konbamide, orbiculamide A, the various
      keramamides, jaspamide eusynstyelamide and more. Important families of non-cyclic
      peptides containing the 6-BrTrp, include the styelins, the conotoxins, the
      cathelicidins and several constrained macrocyclic peptides. Many marine secondary
      BrTrp-containing, non-peptidic metabolites also display a remarkable spectrum of
      bioactivities, which can be harnessed for therapeutic and other purposes.
      Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide
      A, clavicipitic acid, various brominated beta-carbolines. In this review we have
      presented the various synthetic routes leading to the preparation of the five
      BrTrps and many of its derivatives. Also, we have introduced the reader to many
      synthetic routes leading to BrTrp-containing non-peptidic natural products.
      Although the functional role of the various compounds in the human body is only
      poorly understood, its effects were extensively studied. Almost all of these
      compounds exhibit important therapeutic properties e.g. antifungal,
      antimicrobial, antihelmintic, insecticidal ichthyotoxic and anticancer activity.
      In the present review attempts have been made to provide synopsis, synthesis and
      symbiosis of chemical and biological actions, which may provide future guidance
      and facilitate further research in this area.

PMID- 17031474
TI  - Using ensemble classifier to identify membrane protein types.
AB  - Predicting membrane protein type is both an important and challenging topic in
      current molecular and cellular biology. This is because knowledge of membrane
      protein type often provides useful clues for determining, or sheds light upon,
      the function of an uncharacterized membrane protein. With the explosion of newly
      found protein sequences in the post-genomic era, it is in a great demand to
      develop a computational method for fast and reliably identifying the types of
      membrane proteins according to their primary sequences. In this paper, a novel
      classifier, the so-called "ensemble classifier", was introduced. It is formed by
      fusing a set of nearest neighbor (NN) classifiers, each of which is defined in a
      different pseudo amino acid composition space. The type for a query protein is
      determined by the outcome of voting among these constituent individual
      classifiers. It was demonstrated through the self-consistency test, jackknife
      test, and independent dataset test that the ensemble classifier outperformed
      other existing classifiers widely used in biological literatures. It is
      anticipated that the idea of ensemble classifier can also be used to improve the
      prediction quality in classifying other attributes of proteins according to their
      sequences.

PMID- 17031475
TI  - Cellular thiol status-dependent inhibition of tumor cell growth via modulation of
      p27(kip1) translocation and retinoblastoma protein phosphorylation by 1'
      acetoxychavicol acetate.
AB  - 1'-Acetoxychavicol acetate (ACA) has been shown to inhibit tumor cell growth, but
      there is limited information on its effects on cell signaling and the cell cycle
      control pathway. In this study, we sought to determine how ACA alters cell cycle
      and its related control factors in its growth inhibitory effect in Ehrlich
      ascites tumor cells (EATC). ACA caused an accumulation of cells in the G1 phase
      and an inhibition of DNA synthesis, which were reversed by supplementation with N
      acetylcysteine (NAC) or glutathione ethyl ester (GEE). Furthermore, ACA decreased
      hyperphosphorylated Rb levels and increased hypophosphorylated Rb levels. NAC and
      GEE also abolished the decease in Rb phosphorylation by ACA. As Rb
      phosphorylation is regulated by G1 cyclin dependent kinase and CDK inhibitor
      p27(kip1), which is an important regulator of the mammalian cell cycle, we
      estimated the amount of p27(kip1) levels by western blotting. Treatment with ACA
      had virtually no effect on the amount of p27(kip1) levels, but caused a decrease
      in phosphorylated p27(kip1) and an increase in unphosphorylated p27(kip1) as well
      as an increase in the nuclear localization of p27(kip1). These events were
      abolished in the presence of NAC or GEE. These results suggest that in EATC, cell
      growth inhibition elicited by ACA involves decreases in Rb and p27(kip1)
      phosphorylation and an increase in nuclear localization of p27(kip1), and these
      events are dependent on the cellular thiol status.

PMID- 17031476
TI  - Gamma-glutamyl compounds and their enzymatic production using bacterial gamma
      glutamyltranspeptidase.
AB  - Some amino acids and peptides, which have low solubility in water, become much
      more soluble following gamma-glutamylation. Compounds become more stable in the
      blood stream with gamma-glutamylation. Several gamma-glutamyl compounds are known
      to have favorable physiological effects on mammals. Gamma-glutamylation can
      improve taste and can stabilize glutamine in aqueous solution. Because of such
      favorable features, gamma-glutamyl compounds are very attractive. However, only a
      small number of gamma-glutamyl amino acids have been studied although many other
      gamma-glutamyl compounds may have characteristics that will benefit humans. This
      is mainly because gamma-glutamyl compounds have not been readily available. An
      efficient and simple method of producing various gamma-glutamyl compounds,
      especially gamma-glutamyl amino acids, using bacterial gamma
      glutamyltranspeptidase has been developed. With this method, modifications of
      reactive groups of the substrate and energy source such as ATP are not required,
      and a wide-range of gamma-glutamyl compounds can be synthesized. Moreover,
      bacterial gamma-glutamyltranspeptidase, a catalyst for this method, is readily
      available from the strain over-producing this enzyme. The superiority of
      producing gamma-glutamyl compounds with bacterial gamma-glutamyltranspeptidase
      over other methods of production is discussed.

PMID- 17031477
TI  - Multi-layered network structure of amino acid (AA) metabolism characterized by
      each essential AA-deficient condition.
AB  - The concentrations of free amino acids in plasma change coordinately and their
      profiles show distinctive features in various physiological conditions; however,
      their behavior can not always be explained by the conventional flow-based
      metabolic pathway network. In this study, we have revealed the interrelatedness
      of the plasma amino acids and inferred their network structure with threshold
      test analysis and multilevel-digraph analysis methods using the plasma samples of
      rats which are fed diet deficient in single essential amino acid. In the inferred
      network, we could draw some interesting interrelations between plasma amino acids
      as follows: 1) Lysine is located at the top control level and has effects on
      almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in
      the network, which has direct links to the most number of other amino acids. 3)
      Threonine and methionine are interrelated to each other and form a loop
      structure.

PMID- 17031478
TI  - DNA repair Ku proteins in gastric cancer cells and pancreatic acinar cells.
AB  - The DNA repair protein Ku acts as a heterodimer of Ku70 and Ku80 that binds to
      the DNA ends, nicks, or single-to-double-strand transition. It has a crucial role
      for DNA double-strand-break repair. Either Ku70 or Ku80 itself may have a unique
      function that is independent of the other Ku subunit. In this review, the role of
      Ku on cell proliferation and apoptosis will be discussed. Ku acts as a regulator
      of transcription by interacting with the recombination signal binding protein
      Jkappa and the NF-kappaB p50 homodimer to up-regulate p50 expression, which may
      regulate the proliferation of gastric cancer cells. Both Ku70 and Ku80
      expressions are mediated by constitutively activated NF-kappaB and constitutively
      expressed cyclooxygenase-2 in gastric cancer cells, which may be related to
      gastric cell proliferation and carcinogenesis. In addition, nuclear loss of Ku
      may underlie the mechanism of apoptosis in pancreatic acinar cells after
      oxidative stress.

PMID- 17031479
TI  - Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease
      subjects.
AB  - Our aim was to determine changes in free amino acid (FAA) and dipeptide (DP)
      concentrations in probable Alzheimer's disease (pAD) subjects compared with
      control (CT) subjects using liquid chromatography and electrospray ionization
      tandem mass spectrometry (LCMS2). We recruited gender- and age-matched study
      participants based on neurological and neuropsychological assessments. We
      measured FAAs and DPs in cerebrospinal fluid (CSF), plasma and urine using LCMS2
      with selected reaction monitoring (SRM). Imidazole-containing FAAs (histidine,
      methyl-histidine), catecholamines (L-DOPA and dopamine), citrulline, ornithine,
      glycine and antioxidant DPs (carnosine and anserine) accounted for the major
      changes between CT and pAD. Carnosine levels were significantly lower in pAD
      (328.4 +/- 91.31 nmol/dl) than in CT plasma (654.23 +/- 100.61 nmol/dl). In
      contrast, L-DOPA levels were higher in pAD (1400.84 +/- 253.68) than CT (513.10
      +/- 121.61 nmol/dl) plasma. These data underscore the importance of FAA and DP
      metabolism in the pathogenesis of AD. Since our data show changes in
      antioxidants, neurotransmitters and their precursors, or FAA associated with urea
      metabolism in pAD compared with CT, we propose that manipulation of these
      metabolic pathways may be important in preventing AD progression.

PMID- 17031480
TI  - Synthesis of bis-armed amino acid derivatives via the alkylation of ethyl
      isocyanoacetate and the Suzuki-Miyaura cross-coupling reaction.
AB  - Two synthetic routes to bis-armed-alpha-amino acid derivatives are described. The
      first route involves alkylation of dibromo derivatives with ethyl isocyanoacetate
      under phase-transfer catalysis (PTC) conditions. The second route uses a
      palladium-mediated Suzuki-Miyaura cross-coupling reaction between a DL-4
      boronophenylalanine derivative and aromatic diiodo (or dibromo) compounds.

PMID- 17031481
TI  - Selenomethionine induces polyamine biosynthesis in regenerating rat liver tissue.
AB  - Our study was undertaken to elucidate the effects of selenomethionine (SeMet) on
      polyamine metabolism in regenerating rat liver tissue, as useful model of rapidly
      growing normal tissue. We have examined the levels of spermine, spermidine and
      putrescine in liver tissue. At the same time we have evaluated the activities of
      polyamine oxidase (PAO) and diamine oxidase (DAO), the catabolic enzymes of
      polyamine metabolism. The obtained results suggest that polyamine levels in
      regenerating liver tissue, at 7(th) day after two-thirds partial hepatectomy,
      were higher in comparison with control group. The administration of
      selenomethionine to hepatectomized animals during seven days, in a single daily
      dose of 2.5 microg/100 g body weight, increases the amount of spermine and
      spermidine; the level of putrescine does not change under the influence of SeMet
      in regenerating rat liver tissue.PAO activity is lower in regenerating hepatic
      tissue than in control group. Supplementation of hepatectomized animals with
      SeMet significantly decreases the activity of this enzyme. DAO activity was
      significantly higher in hepatectomized and in operated animals treated with SeMet
      compared to the sham-operated and control ones. The differential sensitivity
      observed in our model of highly proliferating normal tissue to SeMet, compared
      with the reported anticancer activity of this molecule is discussed.

PMID- 17031482
TI  - Quantification of free amino acids and dipeptides using isotope dilution liquid
      chromatography and electrospray ionization tandem mass spectrometry.
AB  - Our aim was to develop a liquid chromatography and electrospray ionization tandem
      mass spectrometry (LCMS2) method to measure free amino acid (FAA) and dipeptide
      (DP) concentrations in biological fluids. We synthesized chloroformate
      derivatives of FAA and DP, identified the major precursor ions and used LCMS2 to
      obtain the most intense product ions. Using serial dilutions of unlabeled and
      labeled standards ([2H3]-L-Dopa, homoarginine, homophenylalanine, [15N]-Glutamine
      and [2H3]-methionine), we observed linear relationships in MS response that we
      used to calculate the amounts of FAA and DP in biological samples. This method is
      sensitive with a limit of detection (LOD) for most of the FAAs and DPs tested in
      the 0.05-1 pmol range and is linear over 3-5 orders of magnitude when many
      metabolites were measured simultaneously. Reproducibility and between run or
      daily variations were <10% for most FAAs and DPs. We applied this method to human
      samples and quantitatively measured 21 FAAs and 2 DPs in 200 microl CSF, 31 FAAs
      and 6 DPs in 100 microl plasma, and 23 FAAs and 5 DPs in 200 microl urine. These
      data demonstrate the potential for using LCMS2 to discover changes in FAA and DP
      metabolic pathways that occur during disease pathogenesis.

PMID- 17031483
TI  - Antitumor necrosis factor-induced neutropenia: a case report with double positive
      rechallenges.
AB  - A 50-year-old man with ankylosing spondylitis who developed neutropenia after
      treatment of etanercept, with two positive rechallenges, and after the first
      infliximab infusion, is described. Although leukopenia and neutropenia related to
      etanercept and infliximab have been described as rare adverse events from
      clinical trials data, their mechanism of action are unknown. This patient
      developed recurrent mild neutropenia after exposition of two different antitumor
      necrosis factors; therefore, it seems to be an adverse reaction related to the
      therapeutic group. Doctors should be aware of this potentially severe adverse
      effect in patients treated with antitumor necrosis factor.

PMID- 17031484
TI  - Cervical myelopathy caused by periodontoid synovial pannus in a patient with
      psoriatic arthritis: a case report.
AB  - The atlantoaxial subluxation and the formation of a synovial periodontoid pannus
      are associated with rheumatoid arthritis causing mechanical compression of the
      spinal cord and cervical myelopathy. Atlantoaxial subluxation is very rare in
      psoriatic arthritis (PsA). Even more rare is the formation of a periodontoid
      synovial pannus associated with PsA and signs of myelopathy. In this report,
      cervical myelopathy caused by periodontoid synovial pannus in PsA is described.

PMID- 17031485
TI  - Poor relationship between joint swelling detected on physical examination and
      effusion diagnosed by ultrasonography in glenohumeral joints in patients with
      rheumatoid arthritis.
AB  - The purpose of this study was to assess the relationship between swelling
      detected on physical examination and effusion diagnosed by ultrasonography (US)
      in glenohumeral (GH) joints in patients with rheumatoid arthritis (RA). Fifty
      consecutive patients with RA entered the study and 20 healthy control persons
      formed a control group. Altogether 100 GH joints of the RA patients and 40 of the
      controls were evaluated. The clinical assessments were carried out by one doctor
      and the US investigations by another, and they were blinded to each other's
      results. The clinical examination and US gave similar results in 70 GH joints,
      whereas they differed in the remaining 30 GH joints. The kappa coefficient
      between these investigations was 0.202, showing poor agreement. These results
      showed poor agreement between the clinical assessment of swelling and effusion
      detected by US in GH joints. Therefore, US may considerably improve the accuracy
      of diagnosis of effusion in GH joints, which usually means synovitis in patients
      with RA.

PMID- 17031486
TI  - Anterior vaginal wall prolapse and voiding dysfunction in urogynecology patients.
AB  - We investigated whether women with and without anterior vaginal wall prolapse
      have voiding differences. Women (n=109) who presented to a urogynecology practice
      were categorized into two groups based on anterior vaginal wall prolapse: stages
      0 and 1 and stages 2, 3, and 4. Women with prolapse were older than the women
      without prolapse but the groups were otherwise similar demographically. There was
      a higher rate of activity-related urine loss and use of wetness protection
      amongst women without prolapse. There was no significant difference for urgency
      symptoms or urge incontinence. Urodynamic testing found no significant
      differences for maximal flow rate or maximal urethral closing pressures. Postvoid
      residual volume and detrusor overactivity were not different but approached
      significance. Anterior vaginal wall prolapse of stage 2 or greater was not
      associated with urge incontinence or voiding function in this population. Women
      without prolapse were more likely to report stress incontinence.

PMID- 17031487
TI  - Laparoscopic intraperitoneal repair of high-up urinary bladder fistula: a review
      of 12 cases.
AB  - Conventional abdominal operations for urinary bladder fistula have limitations
      like increased morbidity, more hemorrhage, more postoperative pain, and longer
      hospital stay. Laparoscopic repair of bladder fistula was done to explore the
      potential role of laparoscopic surgery in this field. Twelve women with
      vesicovaginal (11) and vesicouterine (one) fistula, of both gynecological (seven)
      and obstetric (five) origins, were treated by laparoscopic intraperitoneal repair
      between 1991 and 2004. The bladder wall was mobilized and repaired by interrupted
      stitches in single-layer followed by omental interposition. All cases were
      completed laparoscopically without any significant intra- or postoperative
      complication. Gynecological cases were discharged on the fourth day. Urinary
      catheters of all women were removed on the 14th day, and all but one obstetric
      fistula (91% success) were closed. Long-term follow-up confirmed the cure.
      Laparoscopic repair is an excellent method of repairing urinary bladder fistula
      located near the vaginal apex.

PMID- 17031488
TI  - Biomesh (Pelvicol) erosion following repair of anterior vaginal wall prolapse.
AB  - Sparse information is available regarding erosion following biomesh implantation.
      We report two cases of erosion following anterior vaginal wall repair. In both
      cases, the operation was performed as a standard cystocele repair where the
      collagen Pelvicol mesh was anchored to the pubocervical fascia. Both patients had
      signs of erosion shortly after the operation, and both had the mesh removed. In
      one patient, the vaginal epithelium healed spontaneously, whereas the other
      patient had a delayed healing process. The graft was rejected due to intolerance
      to the biomesh or an infection. Our study shows that an erosion following
      implantation of a biomesh may be complicated.

PMID- 17031489
TI  - Tensile strength and host response towards different polypropylene implant
      materials used for augmentation of fascial repair in a rat model.
AB  - We compared inflammatory response, fibrosis and biomechanical properties of
      different polypropylene materials from one manufacturer (Tyco Healthcare) in a
      rat model for primary fascial repair. Full-thickness abdominal wall defects were
      primarily repaired using 'overlay' technique. Multifilament implants were
      Surgipro SPM and SPMW, the latter a wider-weave type of the former. Monofilament
      SPMM implants and polypropylene suture repair (Surgipro II) served as controls.
      Explants were evaluated macroscopically and changes in thickness, shrinkage and
      tensile strength were measured. Inflammatory and connective tissue response was
      assessed on haematoxylin-eosin and Movat stains. Immunohistochemistry was done to
      localise rat macrophages/monocytes. Multifilament materials induced a shorter
      acute inflammatory response and more pronounced chronic inflammatory reaction
      compared to monofilament implants. Macrophages could be found deep in interstices
      7.5 by 12.5 microm. No difference in collagen deposition and neovascularisation
      was observed. At 90 days time point, explants reconstructed with tighter woven
      multifilament SPM were weaker than sutured or SPMM controls. Overall shrinkage of
      10% was comparable for all groups.

PMID- 17031490
TI  - Neurocognitive functioning in patients with first-episode schizophrenia : results
      of a prospective 5-year follow-up study.
AB  - To assess the course of neuropsychological (NP) impairment in schizophrenia, 71
      patients with first episode (FE) schizophrenia and 71 healthy controls were given
      a comprehensive battery of NP tests at index assessment, after a 2-year and after
      a 5-year follow-up period. By means of the z-score standardization, summary
      scores for verbal intelligence (VBI), spatial organisation (SPT), verbal fluency
      (VBF), Verbal learning (VBL), semantic memory (SEM), visual memory (VIM),
      delay/retention rate (DEL), short-term memory (STM), visuomotor processing and
      attention (VSM) and abstraction/flexibility (ABS) were constructed. FE
      schizophrenia patients showed a worse performance compared to controls in all
      areas investigated, most pronounced in VSM, SEM and VBL. In the majority of
      cognitive domains, an improvement was found over the 5-year follow-up period
      without differences between the two groups. However, in VBF patients slightly
      deteriorated whilst controls improved and in memory functions patients improved
      less compared to controls. When controlling for relevant confounders, neither
      conventional nor atypical neuroleptics showed a deleterious influence on NP
      performance, except on VBF. Our data suggest that NP impairment is already
      present at the onset of the illness and remains stable over the early course of
      schizophrenia.

PMID- 17031491
TI  - P38 MAPK protects against TNF-alpha-provoked apoptosis in LNCaP prostatic cancer
      cells.
AB  - PURPOSE: One of the most relevant aspects in cell death regulation is the
      signalling of apoptosis by the serine/threonine kinases MAPKs. The aim of this
      study was to investigate the effects of TNF-alpha stimulation on MAPK activation,
      and the pro- or anti-apoptotic role of these kinases in LNCaP and PC3 cells.
      MATERIAL AND METHODS: Treatments were carried out using several TNF-alpha
      concentrations, as well as specific pharmacological inhibitors of MAPKs.
      Apoptosis rates were evaluated by DAPI staining and flow cytometry. MAPK
      phosphorylation/activation was measured by Western blot. RESULTS: TNF-alpha
      induced apoptosis in a dose-dependent manner in LNCaP but not in PC3 cells. The
      MAPK inhibitors revealed that the apoptotic rate in LNCaP cells increased
      significantly following p38 inhibition. The kinase inhibitors failed to cause
      changes in apoptosis in PC3 cells. CONCLUSIONS: The potentiation of apoptosis by
      p38 inhibition points to this kinase as a possible target for the treatment of
      androgen-dependent prostatic cancer.

PMID- 17031492
TI  - Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes.
AB  - It has been well established that FADD plays a critical role in the membrane
      bound death-inducing signaling complexes. Herein, we report that endogenous FADD
      could interact with ectopic or endogenous RTN3/HAP. ER-bound RTN3 protein
      recruited endogenous FADD to the ER membrane and subsequently initiated caspase-8
      cascade, including activation of caspase-8, processing of Bid and release of
      cytochrome c from mitochondria. Furthermore, we demonstrated that endogenous FADD
      was recruited by ER-bound endogenous RTN3 to the ER membrane under the
      tunicamycin stimulation. The dominant negative form of FADD containing DD could
      abolish these RTN3 generated events in the caspase-8 cascade. Moreover, we found
      that RTN3 induced caspase-9 processing was only partially resulted from caspase-8
      activation (data unshown), indicating that multiple caspase cascades participated
      in the apoptosis from RTN3 over-expression. Furthermore, NogoB/ASY, a homologue
      of RTN3 and a potential RTN3 interacting protein, also associated with FADD and
      induced cytochrome c release in a FADD dependent manner.

PMID- 17031493
TI  - Caspase-8 dependent TRAIL-induced apoptosis in cancer cell lines is inhibited by
      vitamin C and catalase.
AB  - TNF-related apoptosis-inducing ligand (TRAIL/ Apo-2L) is a member of the TNF
      family of apoptosis-inducing proteins that initiates apoptosis in a variety of
      neoplastic cells while displaying minimal or absent cytotoxicity to most normal
      cells. Therefore, TRAIL is currently considered a promising target to develop
      anti-cancer therapies. TRAIL-receptor ligation recruits and activates pro-caspase
      8, which in turn activates proteins that mediate disruption of the mitochondrial
      membranes. These events lead to the nuclear and cytosolic damage characteristic
      of apoptosis. Here we report that TRAIL-induced apoptosis is mediated by
      oxidative stress and that vitamin C (ascorbic acid), a potent nutritional
      antioxidant, protects cancer cell lines from apoptosis induced by TRAIL. Vitamin
      C impedes the elevation of reactive oxygen species (ROS) levels induced by TRAIL
      and impairs caspase-8 activation. We found that the removal of hydrogen peroxide
      by extracellular catalase during TRAIL-induced apoptosis also impairs caspase-8
      activation. These data suggest that hydrogen peroxide is produced during TRAIL
      receptor ligation, and that the increase of intracellular ROS regulates the
      activation of caspase-8 during apoptosis. Additionally we propose a mechanism by
      which cancer cells might resist apoptosis via TRAIL, by the intake of the
      nutritional antioxidant vitamin C.

PMID- 17031494
TI  - Chromosome banding in three species of Hypsiboas (Hylidae, Hylinae), with special
      reference to a new case of B-chromosome in anuran frogs and to the reduction of
      the diploid number of 2n = 24 to 2n = 22 in the genus.
AB  - The chromosomes of hylids Hypsiboas albopunctatus, H. raniceps, and H. crepitans
      from Brazil were analyzed with standard and differential staining techniques. The
      former species presented 2n = 22 and 2n = 23 karyotypes, the odd diploid number
      is due to the presence of an extra element interpreted as B chromosome. Although
      morphologically very similar to the small-sized chromosomes of the A complement,
      the B was promptly recognized, even under standard staining, on the basis of some
      characteristics that are usually attributed to this particular class of
      chromosomes. The two other species have 2n = 24, which is the chromosome number
      usually found in the species of Hypsiboas karyotyped so far. This means that 2n =
      22 is a deviant diploid number, resulted from a structural rearrangement,
      altering the chromosome number of 2n = 24 to 2n = 22. Based on new chromosome
      data, some possibilities were evaluated for the origin of B chromosome in
      Hypsiboas albopunctatus, as well as the karyotypic evolution in the genus,
      leading to the reduction in the diploid number of 2n = 24 to 2n = 22.

PMID- 17031495
TI  - Isolation and characterization of sex chromosome rearrangements generating male
      muscle dystrophy and female abnormal oogenesis in the silkworm, Bombyx mori.
AB  - In deletion-mapping of W-specific RAPD (W-RAPD) markers and putative female
      determinant gene (Fem), we used X-ray irradiation to break the translocation
      carrying W chromosome (W( Ze )). We succeeded in obtaining a fragment of the W(
      Ze ) chromosome designated as Ze (W), having 3 of 12 W-RAPD markers (W-Bonsai, W
      Yukemuri-S, W-Yukemuri-L). Inheritance of the Ze (W) fragment by males indicates
      that it does not include the Fem gene. On the basis of these results, we
      determined the relative positions of W-Yukemuri-S and W-Yukemuri-L, and we
      narrowed down the region where Fem gene is located. In addition to the Ze (W)
      fragment, the Z chromosome was also broken into a large fragment (Z(1)) having
      the +( sch ) (1-21.5) and a small fragment (Z(2)) having the +( od ) (1-49.6).
      Moreover, a new chromosomal fragment (Ze (W)Z(2)) was generated by a fusion event
      between the Ze (W) and the Z(2) fragments. We analyzed the genetic behavior of
      the Z(1) fragment and the Ze (W)Z(2) fragment during male (Z/Z(1) Ze (W)Z(2)) and
      female (Z(1) Ze (W)Z(2)/W) meiosis using phenotypic markers. It was observed that
      the Z(1) fragment and the Z or the W chromosomes separate without fail. On the
      other hand, non-disjunction between the Ze (W)Z(2) fragment and the Z chromosome
      and also between the Ze (W)Z(2) fragment and the W chromosome occurred.
      Furthermore, the females (2A: Z/Ze (W)Z(2)/W) and males (2A: Z/Z(1)) resulting
      from non-disjunction between the Ze (W)Z(2) fragment and the W chromosome had
      phenotypic defects: namely, females exhibited abnormal oogenesis and males were
      flapless due to abnormal indirect flight muscle structure. These results suggest
      that Z(2) region of the Z chromosome contains dose-sensitive gene(s), which are
      involved in oogenesis and indirect flight muscle development.

PMID- 17031496
TI  - Bayesian analysis of paired survival data using a bivariate exponential
      distribution.
AB  - We consider a Bayesian analysis method of paired survival data using a bivariate
      exponential model proposed by Moran (1967, Biometrika 54:385-394). Important
      features of Moran's model include that the marginal distributions are exponential
      and the range of the correlation coefficient is between 0 and 1. These contrast
      with the popular exponential model with gamma frailty. Despite these nice
      properties, statistical analysis with Moran's model has been hampered by lack of
      a closed form likelihood function. In this paper, we introduce a latent variable
      to circumvent the difficulty in the Bayesian computation. We also consider a
      model checking procedure using the predictive Bayesian P-value.

PMID- 17031497
TI  - A flexible semiparametric transformation model for survival data.
AB  - I suggest an extension of the semiparametric transformation model that specifies
      a time-varying regression structure for the transformation, and thus allows time
      varying structure in the data. Special cases include a stratified version of the
      usual semiparametric transformation model. The model can be thought of as
      specifying a first order Taylor expansion of a completely flexible baseline.
      Large sample properties are derived and estimators of the asymptotic variances of
      the regression coefficients are given. The method is illustrated by a worked
      example and a small simulation study. A goodness of fit procedure for testing if
      the regression effects lead to a satisfactory fit is also suggested.

PMID- 17031498
TI  - Dynamic survival models with spatial frailty.
AB  - In many survival studies, covariates effects are time-varying and there is
      presence of spatial effects. Dynamic models can be used to cope with the
      variations of the effects and spatial components are introduced to handle spatial
      variation. This paper proposes a methodology to simultaneously introduce these
      components into the model. A number of specifications for the spatial components
      are considered. Estimation is performed via a Bayesian approach through Markov
      chain Monte Carlo methods. Models are compared to assess relevance of their
      components. Analysis of a real data set is performed, showing the relevance of
      both time-varying covariate effects and spatial components. Extensions to the
      methodology are proposed along with concluding remarks.

PMID- 17031499
TI  - A semiparametric additive rates model for recurrent event data.
AB  - Recurrent event data often arise in biomedical studies, with examples including
      hospitalizations, infections, and treatment failures. In observational studies,
      it is often of interest to estimate the effects of covariates on the marginal
      recurrent event rate. The majority of existing rate regression methods assume
      multiplicative covariate effects. We propose a semiparametric model for the
      marginal recurrent event rate, wherein the covariates are assumed to add to the
      unspecified baseline rate. Covariate effects are summarized by rate differences,
      meaning that the absolute effect on the rate function can be determined from the
      regression coefficient alone. We describe modifications of the proposed method to
      accommodate a terminating event (e.g., death). Proposed estimators of the
      regression parameters and baseline rate are shown to be consistent and
      asymptotically Gaussian. Simulation studies demonstrate that the asymptotic
      approximations are accurate in finite samples. The proposed methods are applied
      to a state-wide kidney transplant data set.

PMID- 17031500
TI  - Computerized adaptive testing of diabetes impact: a feasibility study of
      Hispanics and non-Hispanics in an active clinic population.
AB  - BACKGROUND: Diabetes is a leading cause of death and disability in the US and is
      twice as common among Hispanic Americans as non-Hispanics. The societal costs of
      diabetes provide an impetus for developing tools that can improve patient care
      and delay or prevent diabetes complications. METHODS: We implemented a
      feasibility study of a Computerized Adaptive Test (CAT) to measure diabetes
      impact using a sample of 103 English- and 97 Spanish-speaking patients (mean age
      = 56.5, 66.5% female) in a community medical center with a high proportion of
      minority patients (28% African-American). The 37 items of the Diabetes Impact
      Survey were translated using forward-backward translation and cognitive
      debriefing. Participants were randomized to receive either the full-length tool
      or the Diabetes-CAT first, in the patient's native language. RESULTS: The number
      of items and the amount of time to complete the survey for the CAT was reduced to
      one-sixth the amount for the full-length tool in both languages, across disease
      severity. Confirmatory Factor Analysis confirmed that the Diabetes Impact Survey
      is unidimensional. The Diabetes-CAT demonstrated acceptable internal consistency
      reliability, construct validity, and discriminant validity in the overall sample,
      although subgroup analyses suggested that the English sample data evidenced
      higher levels of reliability and validity than the Spanish sample and issues with
      discriminant validity in the Spanish sample. Differential Item Function analysis
      revealed differences in responses tendencies by language group in 3 of the 37
      items. Participant interviews suggested that the Spanish-speaking patients
      generally preferred the paper survey to the computer-assisted tool, and were
      twice as likely to experience difficulties understanding the items. CONCLUSIONS:
      While the Diabetes-CAT demonstrated clear advantages in reducing respondent
      burden as compared to the full-length tool, simplifying the item bank will be
      necessary for enhancing the feasibility of the Diabetes-CAT for use with low
      literacy patients.

PMID- 17031501
TI  - Testing the interval-level measurement property of multi-item visual analogue
      scales.
AB  - BACKGROUND: Conditions were studied that may invalidate health-state values
      derived from the visual analogue scale (VAS). METHODS: Respondents were asked to
      place cards with descriptions of EQ-5D health states on a 20 cm EuroQol VAS and
      modified versions of it, positioning them such that the distances between the
      states reflect their valuation for these states. Anchor-point bias was examined
      using the standard EuroQol VAS (n = 212) and a modified version (n = 97) with a
      different lower anchor. Context bias was examined in another group of respondents
      (n = 112) who valued three different sets of EQ-5D health states. Marker bias was
      studied in yet another group of respondents (n = 100) who placed the same EQ-5D
      states on the standard EuroQol VAS and on a modified VAS without anchors,
      categories, or measurement markers. RESULTS: No indication for the existence of
      the anchor-point and the marker bias was found. However, the VAS valuations were
      significantly affected by the context of the set of health states in the scaling
      task. CONCLUSION: Advanced methodologies should be incorporated in VAS valuation
      studies to deal with the context bias.

PMID- 17031502
TI  - The ORTHO BC-SAT--a satisfaction questionnaire for women using hormonal
      contraceptives.
AB  - OBJECTIVE: To assess the reliability and validity of the ORTHO Birth Control
      Satisfaction Assessment Tool (ORTHO BC-SAT). DESIGN: 339 women using 1 of 4
      hormonal birth control methods (oral contraceptives, transdermal patch, vaginal
      ring, injections), completed the questionnaire 1-2 times. MATERIALS AND METHODS:
      The questionnaire was developed based on findings from the literature, focus
      groups, and interviews. Internal consistency reliability, test-retest
      reliability, construct validity, and known groups validity were evaluated.
      RESULTS: Based on variable clustering, 8 domains were identified (Ease of
      Use/Convenience, Compliance, Lifestyle Impact, Symptom/Side Effect Bother,
      Menstrual Impact, Future Fertility Concerns, Assurance/Confidence, Overall
      Satisfaction). Internal consistency reliability was demonstrated with Cronbach's
      alpha values ranging from 0.70 to 0.89. All multi-item scales reported acceptable
      test-retest reliability (0.79-0.87). Construct validity was demonstrated by
      support of a hypothesized pattern of correlations. Known groups validity was
      confirmed by examining scale scores of women categorized by levels of symptom
      bother. As expected, women with the least amount of bother reported higher scores
      on all satisfaction scales than those with higher bother (p < 0.0001), except on
      Future Fertility Concerns (p = 0.27). CONCLUSION: Our results support the
      reliability and validity of the ORTHO BC-SAT. It may be used in future studies to
      evaluate satisfaction among hormonal contraceptive users.

PMID- 17031503
TI  - The clinical significance of adaptation to changing health: a meta-analysis of
      response shift.
AB  - AIMS: When individuals experience changes in their health states, they may alter
      their internal standards, values, or conceptualization of quality of life (QOL).
      Such 'response shifts' can affect or distort QOL outcome measurement, which is of
      particular concern when evaluating medical or psychosocial interventions.
      Although clinicians and researchers acknowledge the occurrence of response
      shifts, little is known about the magnitude and clinical significance of those
      effects. To fill this gap in knowledge about response shift phenomena, we
      performed a meta-analysis on published QOL articles on response shift. METHODS:
      Extensive literature searches and multiple contacts with researchers yielded a
      collection of 494 articles for potential reviewing. We retained only published
      longitudinal studies that measured response shift, resulting in 26, of which 19
      reported the requisite data for computing an effect size (ES). We calculated and
      compared the ESs for each study with regard to potential moderator variables: the
      QOL domains measured, disease group investigated, sample size, and response shift
      method used. We rated studies for quality to allow ES weighting. RESULTS: When we
      examined ES absolute values, we found that ES magnitude was small, with the
      largest ESs detected for fatigue, followed by global QOL, physical role
      limitation, psychological well-being, and pain (mean absolute value(ES(weighted))
      = 0.32, 0.30, 0.24, 0.12, and 0.08, respectively). ESs varied considerably in
      direction. Aggregating raw ES scores over all studies led to positive and
      negative values canceling each other out (mean directional ES(weighted) = 0.17,
      0.02, -0.01, 0.06, and 0.02, respectively). We found little evidence of an effect
      for the moderator variables examined. CONCLUSIONS: A definitive conclusion on the
      clinical significance of response shift cannot currently be drawn from existing
      studies. For a number of reasons, ES estimates were primarily based on then-test
      results, a method that is not without criticism, such as its susceptibility to
      recall bias. We recommend a standardized approach for reporting results of future
      response shift research to advance the field and to facilitate interpretation and
      comparisons across studies.

PMID- 17031504
TI  - Fibromuscular dysplasia of the renal arteries: a radiological review.
AB  - Fibromuscular dysplasia is the most common cause of renovascular hypertension in
      young patients. Digital subtraction angiography is still the best investigation
      used to determine the location, extent and complication of renal artery
      involvement. String of beads appearance (reflecting multiple stenoses),
      aneurysms, focal or tubular stenosis are classic angiographic appearances. The
      aim of this pictorial essay is to illustrate the various imaging findings of
      renal artery fibromuscular dysplasia.

PMID- 17031505
TI  - Endothelial dysfunction in geriatric diabetic patients: the role of
      microalbuminuria in elderly type 2 diabetic patients? A randomized controlled
      study.
AB  - BACKGROUNDS/AIMS: Microalbuminuria is considered a marker of extensive
      endothelial dysfunction and is associated with excess of other cardiovascular
      risk factors. Our aim is to assess the importance of the presence of
      microalbuminuria in elderly diabetic patients. METHODS: A total of 40
      normotensive elderly type 2 diabetic patients of both genders with mean age >65
      years were randomly included and were further subdivided according to the
      presence of persistent microalbuminuria into microalbuminuric and
      normoalbuminuric groups. PATIENTS AND METHODS: All patients in both groups were
      subjected to thorough clinical and laboratory investigations including the assay
      of serum thrombomodulin (TM) and glycosylated hemoglobin level. Early-morning
      midstream urine samples were evaluated for levels of beta 2 microglobulin, alpha
      1 microglobulin, TM, and N-acetyl-beta-D-glucosaminidase (NAG). RESULTS: There
      was no significant difference between both groups regarding the clinical
      demographic characteristics. There were statistically significant higher values
      for glycosylated hemoglobin percentage, serum triglycerides and serum TM and
      urinary B2 microglobulin, urinary alpha 1 microglobulin, urinary NAG and urinary
      thrombomodulin in microalbuminuric group in comparison to normoalbuminuric group
      (P < 0.05). CONCLUSION: Microalbuminuria is associated with markers of
      endothelial dysfunction in elderly normotensive type 2 diabetic patients. We
      recommend incorporation of periodic testing for microalbuminuria in this sector
      of patients.

PMID- 17031506
TI  - Unexplained hematuria during pregnancy: right-sided nutcracker phenomenon.
AB  - We report a case of hematuria in a pregnant patient caused by right renal vein
      hypertension, as a result of compression of right renal, the inferior caval and
      the right gonadal veins because of posterior displacement of the pancreas caused
      by the presence of the gravid uterus. Hematuria resolved after a cesarean
      delivery. This condition has not been, to our knowledge, previously described.

PMID- 17031507
TI  - Suspended particulate matter distribution in rural-industrial Satna and in urban
      industrial South Delhi.
AB  - An air quality sampling program was designed and implemented to collect the
      baseline concentrations of respirable suspended particulates (RSP = PM10), non
      respirable suspended particulates (NRSP) and fine suspended particulates (FSP =
      PM2.5). Over a three-week period, a 24-h average concentrations were calculated
      from the samples collected at an industrial site in Southern Delhi and compared
      to datasets collected in Satna by Envirotech Limited, Okhla, Delhi in order to
      establish the characteristic difference in emission patterns. PM2.5, PM10, and
      total suspended particulates (TSP) concentrations at Satna were 20.5 +/- 6.0,
      102.1 +/- 41.1, and 387.6 +/- 222.4 microg m(-3) and at Delhi were 126.7 +/-
      28.6, 268.6 +/- 39.1, and 687.7 +/- 117.4 microg m(-3). Values at Delhi were well
      above the standard limit for 24-h PM2.5 United States National Ambient Air
      Quality Standards (USNAAQS; 65 microg m(-3)), while values at Satna were under
      the standard limit. Results were compared with various worldwide studies. These
      comparisons suggest an immediate need for the promulgation of new PM2.5
      standards. The position of PM10 in Delhi is drastic and needs an immediate
      attention. PM10 levels at Delhi were also well above the standard limit for 24-h
      PM10 National Ambient Air Quality Standards (NAAQS; 150 microg m(-3)), while
      levels at Satna remained under the standard limit. PM2.5/PM10 values were also
      calculated to determine PM2.5 contribution. At Satna, PM2.5 contribution to PM10
      was only 20% compared to 47% in Delhi. TSP values at Delhi were well above, while
      TSP values at Satna were under, the standard limit for 24-h TSP NAAQS (500 microg
      m(-3)). At Satna, the PM10 contribution to TSP was only 26% compared to 39% in
      Delhi. The correlation between PM10, PM2.5, and TSP were also calculated in order
      to gain an insight to their sources. Both in Satna and in Delhi, none of the
      sources was dominant a varied pattern of emissions was obtained, showing the
      presence of heterogeneous emission density and that nonrespirable suspended
      particulate (NRSP) formed the greatest part of the particulate load.

PMID- 17031508
TI  - Levels of PAHs in the soils of Belgrade and its environs.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were analysed in 39 soil samples (0-10 cm
      upper layer) collected in Belgrade, the capital of Serbia. The sampling sites
      were randomly selected from urban, urban/recreational and rural areas; the
      samples were collected in April and December 2003 and July and October 2004. The
      sum of the 16 PAHs corresponding to the recreational zone (298 microg/kg) was
      close to the urban zone (375 microg/kg). Mean soil SigmaPAH concentration from
      rural areas was 18 microg/kg dry weight. Comparing to values observed in the
      urbanized locations around the world, the overall levels of PAHs in this study
      are low. The PAH ratios obtained pointed to a domination of pyrogenically formed
      PAHs in the examined soils. The dominant PAHs in soil samples in urban zones were
      fluoranthene, benz[a]anthracene, phenanthrene and pyrene, mostly emitted from
      noncatalyst vehicles which are still in use in Serbia. The total carcinogenic
      potency for each sampling site was calculated. Regardless of the used
      carcinogenic activity factors, carcinogenic potency of 7 sites were 3-9 times
      higher than the reference ones indicating the increased carcinogenic burden of
      soils from these sites.

PMID- 17031509
TI  - Concentrations and modes of occurrence of trace elements in the Late Permian
      coals from the Puan Coalfield, southwestern Guizhou, China.
AB  - The concentration, mode of occurrence, and origin of trace elements in the Late
      Permian coals from the Puan Coalfield, southwestern Guizhou, China, were examined
      using inductively coupled plasma-mass spectrometry (ICP-MS), X-ray fluorescence
      (XRF), cold-vapor atomic absorption spectrometry (CV-AAS), ion-selective
      electrode method (ISE), sequential chemical extraction procedure (SCEP), scanning
      electron microscopy equipped with energy-dispersive X-ray (SEM-EDX), and optical
      microscope. Results show that minerals in the No. 2 Coal from the Puan Coalfield
      were mainly made up of epigenetic pyrite of low-temperature hydrothermal fluid
      origin and kaolinite of detrital terrigenous origin. Elements including As (36.9
      microg/g), Cd (10.2 microg/g), Cr (167.3 microg/g), Cu (365.4 microg/g), Hg (2.82
      microg/g), Mo (92.6 microg/g), Ni (82.6 microg/g), Pb (184.6 microg/g), Se (6.23
      microg/g), Zn (242.3 microg/g), and U (132.7 microg/g) are significantly enriched
      in the No. 2 Coal from the Puan Coalfield. However, concentrations of trace
      elements in the other four coals, the No. 1, No. 8, No. 11, and No. 18 Coals,
      were close to the usual ranges found for Guizhou of China, China, and USA.
      Results of SEM-EDX and SCEP showed that As, Cd, Hg, Mo, Ni, Pb, and Zn occur
      mainly in veined pyrite, while Cr, Cu, and U distribute mainly in kaolinite,
      indicating that the low-temperature hydrothermal fluid and detrital materials of
      terrigenous origin are the main contributors to the enrichment of these trace
      elements in the No. 2 Coal.

PMID- 17031510
TI  - Long-term safety and efficacy of infliximab therapy in refractory uveitis due to
      Behcet's disease.
AB  - PURPOSE: To evaluate the long-term safety and efficacy of infliximab therapy for
      refractory uveitis associated with Behcet's disease (BD). METHODS: We
      prospectively enrolled six patients who failed to respond to conventional
      immunosuppressive treatment. Infliximab infusions (5 mg/kg) were administered at
      weeks 0, 2, 6, and then every 8 weeks. The outcome variables were visual acuity,
      control of inflammation, reduction of macular edema, tapering of
      immunosuppressive therapy, and adverse effects. RESULTS: The follow-up period
      ranged from 16 to 36 months (mean +/- SD, 23 +/- 7.4 months). The number of
      infliximab infusions ranged from 10 to 23 (14 +/- 4.6). By the 2-month follow-up,
      all patients had achieved remission, the cystoid macular edema had resolved, and
      visual acuity had improved dramatically. Throughout the follow-up period, three
      patients remained attack-free. One patient had one relapse, and another patient
      had two relapses before the scheduled infusions; all three relapses resolved
      rapidly after the subsequent infusion. One patient developed five relapses, and
      infusions at 6-week intervals were necessary to achieve sustained remission. At
      the end of the follow-up period, visual acuity improved in five patients.
      Concomitant immunosuppressive therapy was substantially reduced. Antinuclear
      antibodies developed in two patients who received 17 and 23 infusions. No major
      adverse effects requiring withdrawal of infliximab were observed. CONCLUSION:
      Infliximab is efficient and safe for long-term treatment of refractory uveitis
      associated with BD. Repeated infusions are required to maintain long-term
      remission.

PMID- 17031511
TI  - A novel drought-inducible gene, ATAF1, encodes a NAC family protein that
      negatively regulates the expression of stress-responsive genes in Arabidopsis.
AB  - NAC proteins are plant-specific transcriptional regulators. ATAF1 was one of the
      first identified NAC proteins in Arabidopsis. In present study, we characterized
      the ATAF1 expression and biological function in response to water deficit stress.
      ATAF1 mRNA expression was strongly induced by dehydration and abscisic acid (ABA)
      treatment, but inhibited by water treatment, suggesting a general role in drought
      stress responses. Transient expression analysis in onion epidermal cells
      indicated the nuclear localization for the ATAF1::GFP fusion protein. Yeast
      transactivation analysis showed that ATAF1 had ability to activate reporter gene
      expression. Furthermore, domain deletion analysis revealed that the ATAF1
      transactivation activity was conferred by its C-terminal domain. When ATAF1 gene
      was knocked out by T-DNA insertions, Arabidopsis ataf1-1 and ataf1-2 mutants
      displayed a recovery rate about seven times higher than wild-type plants in
      drought response test. This ataf1 phenotype was coincident with the enhanced
      expression of stress responsive marker genes, such as COR47, ERD10, KIN1, RD22
      and RD29A under drought stress. Above evidences suggest that ATAF1, as a
      transcriptional regulator, negatively regulates the expression of stress
      responsive genes under drought stress in Arabidopsis.

PMID- 17031512
TI  - ABI4 mediates the effects of exogenous trehalose on Arabidopsis growth and starch
      breakdown.
AB  - The disaccharide trehalose has dramatic effects on plant metabolism, growth and
      development. Arabidopsis seedlings grown on trehalose-containing medium without
      sucrose display increased expression of the starch synthesis gene ApL3, hyper
      accumulation of starch in the cotyledons and inhibition of root growth. Here we
      show that the ABI4 transcription factor mediates the effects of trehalose on
      starch metabolism and growth, independently of abscisic acid (ABA) synthesis and
      hexokinase (HXK1) signaling. Surprisingly, although the abi4 mutation partially
      rescued trehalose inhibition of root elongation, ApL3 expression levels were
      still enhanced. Gene expression analysis suggests that trehalose affects both
      starch synthesis and starch breakdown. The expression of genes involved in starch
      breakdown, such as SEX1 and the beta-amylase gene BMY8/BAM3, was strongly down
      regulated in WT plants grown on trehalose but not in abi4 mutants. Addition of
      trehalose to liquid-grown WT seedlings also significantly reduced SEX1 expression
      after 6 h. Bypassing the need for starch breakdown by growth in continuous light
      or addition of sucrose rescued root growth on trehalose medium similar to the
      abi4 mutation. These results suggest that inhibition of starch mobilization
      rather than increased synthesis is involved in growth inhibition by exogenous
      trehalose. Trehalose also significantly enhanced ABI4 expression but reduced its
      sucrose induction, providing a possible molecular mechanism for the trehalose
      effect on plant gene expression and growth.

PMID- 17031513
TI  - The late pollen actins are essential for normal male and female development in
      Arabidopsis.
AB  - In angiosperms the late pollen actins (LPAs) are strongly expressed in mature
      pollen and pollen tubes and at much lower levels in ovules. Four Arabidopsis
      lines with homozygous knockout mutations in the four individual LPA genes
      displayed normal flowers, pollen, and seed set. However, when all four LPAs were
      silenced simultaneously with a single RNA interference (RNAi) construct targeting
      the 3'UTR of each mRNA, obvious reproductive defects were observed. Western
      analysis of various Late Pollen actin RNA interference (LPRi) epialleles showed
      total LPA protein and RNA expression levels were knocked down from 0% to 95%
      compared to wild-type levels. Reciprocal crosses with the RNAi lines demonstrated
      that lowered LPA expression was associated with defects in both male and female
      fertility. Strong epialleles showed significant reductions in normal silique and
      seed production and were nearly sterile. Dissection of the siliques from moderate
      LPRi epialleles revealed many unfertilized ovules, increased numbers of aborted
      seeds, and decreased numbers of healthy seeds. Microscopic analysis of LPRi
      pollen indicated that the pollen shape and size were normal, but pollen
      germinated poorly. While multiple LPA genes may have some functional redundancy,
      the combined expression of multiple LPA genes appears essential to normal male
      and female reproductive development.

PMID- 17031514
TI  - The tumor-growth inhibitory activity of flavanone and 2'-OH flavanone in vitro
      and in vivo through induction of cell cycle arrest and suppression of cyclins and
      CDKs.
AB  - Natural products, including flavonoids, are suggested to be involved in the
      protective effects of fruits and vegetables against cancer. However, studies
      concerning the effect of flavonoids frequently lacked data regarding to
      flavanones. In this study, we investigated the inhibitory effect of flavanone
      compounds, including flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone,
      naringin and naringenin, on cell growth of various cancer cells. We determined
      that flavanone and 2'-OH flavanone inhibited cell growth of A549, LLC, AGS, SK
      Hepl and HA22T cancer cells, while other flavanones showed little or no
      inhibition. We evaluated growth-inhibitory activity of flavanone and 2'-OH
      flavanone against highly proliferative human lung cancer cells (A549) via
      anchorage-independent and -dependent colony formation assay, and further showed
      that treatment of flavanone resulted in a G1 cell cycle arrest with reduction of
      cyclin D, E and cyclin-dependent kinase (CDK) 2, while treatment of 2'-OH
      flavanone led to a G2/M phase accumulation with reduction of cyclin B, D and
      Cdc2. Moreover, we demonstrated the improvement effect of flavanone and 2'-OH
      flavanone with anti-cancer drug, doxorubicin, on A549 cells. Finally, flavanone
      and 2'-OH flavanone were evidenced by its inhibition on the growth of A549 and
      Lewis lung carcinoma cells in vivo.

PMID- 17031515
TI  - In vitro modeling of the structure-activity determinants of anthracycline
      cardiotoxicity.
AB  - Doxorubicin and other anthracyclines rank among the most effective anticancer
      drugs ever developed. Unfortunately, the clinical use of anthracyclines is
      limited by a dose-related life-threatening cardiotoxicity. Understanding how
      anthracyclines induce cardiotoxicity is essential to improve their therapeutic
      index or to identify analogues that retain activity while also inducing less
      severe cardiac damage. Here, we briefly review the prevailing hypotheses on
      anthracycline-induced cardiotoxicity. We also attempt to establish cause-and
      effect relations between the structure of a given anthracycline and its
      cardiotoxicity when administered as a single agent or during the course of
      multiagent chemotherapies. Finally, we discuss how the hypotheses generated by
      preclinical models eventually translate into phase I-II clinical trials.

PMID- 17031516
TI  - Frailty modelling of colorectal cancer incidence in Norway: indications that
      individual heterogeneity in risk is related to birth cohort.
AB  - Some cancer types level off or decrease in incidence at older age groups, not
      following the Weibull hazard rate. This stagnation can be explained by the
      frailty model, which describes the population effect of mixing individuals who
      are susceptible, with high risk of cancer, with those that are "non-susceptible",
      with a low risk of cancer even in the oldest age groups. The aim of the study was
      to apply a frailty model on colorectal cancer incidence data for the Norwegian
      population aged 40-99 years, diagnosed 1956-2000. The model provided an
      acceptable fit to the data. The estimated proportion of susceptibles increased
      from about 5% to about 24% from the first cohort (1851-1855) to the last cohort
      (1946-1950), in line with the rise in incidence of the disease during this
      period. According to the frailty modelling, the estimated number of genetic
      events necessary for a malignant lesion to develop in the colorectum is seven to
      eight, which accords with the present knowledge regarding colorectal
      carcinogenesis. The frailty phenomenon may thus be present in this cancer form.
      The findings indicate that it is possible to model the development of colorectal
      cancer in the population based on large heterogeneity in risk between
      individuals, in such a manner that a small group of individuals are susceptible
      to develop the disease, whereas the remaining majority have a low susceptibility.

PMID- 17031517
TI  - Classification of surgical procedures for epidemiologic assessment of sporadic
      Creutzfeldt-Jakob disease transmission by surgery.
AB  - BACKGROUND: In this preparatory phase of a case-control study, we propose and
      evaluate a new tool for classifying surgical procedures (SPs) in categories
      useful for epidemiologic research on surgical transmission of sporadic
      Creutzfeldt-Jakob disease (sCJD). METHODS: All SPs reported to the Swedish
      National Hospital Discharge Registry in the period 1974-2002, and undergone by
      212 Swedish patients with registered diagnosis of CJD at death, hospital
      discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence
      matched controls and 1340 randomly chosen population controls, were reclassified
      into one of six categories of hypothetical transmission risk level. For that
      purpose the following two attributes were used: non-disposable instruments
      involved; and highest assigned ad-hoc risk level for four tissues or anatomical
      structures contacting such instruments. RESULTS: A total of 1170 different SP
      codes were reclassified as follows: 3.1% in the high-risk, 59.1% in the lower
      risk, 24.4% in the lowest-risk, and 2.1% in the no-risk groups, with 11.3%
      procedures negatively defined by rubric as "other than..." being assigned to two
      spurious diluted-high and diluted-lower risk categories. The high-risk group
      mainly comprised neurosurgical (53%) and ophthalmic (39%) procedures. Sensitivity
      of neurosurgery and of ophthalmic surgery excluding neurosurgery, for the high-
      and diluted-high risk vs. other categories was 46% and 84%, while specificity was
      98% and 95%, respectively. Sensitivity analysis based on these indices revealed
      that non-significant odds ratio effects of 1.4 and 1.3 for neurosurgery and
      ophthalmic surgery corresponded to statistically significant values of 5.1 after
      reclassification. CONCLUSIONS: This classification might contribute to quantify
      effects masked by use of body-system SP-categories in case-control studies on
      sCJD transmission by surgery.

PMID- 17031518
TI  - Effect of genetic variation in the leptin gene promoter and the leptin receptor
      gene on obesity risk in a population-based case-control study in Spain.
AB  - There are no good genetic markers for incorporating the study of genetic
      susceptibility to obesity in epidemiological studies. In animal models, the
      leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very
      important in obesity because leptin functions as a negative feedback signal in
      regulating body-weight through reducing food intake and stimulating energy
      expenditure. In humans, several polymorphisms in these genes have been described.
      However, their association with obesity is still very controversial because there
      are no good case-control studies designed to specifically test this association.
      Our objective has been to conduct a population-based case-control study to
      estimate the risk of obesity arising from the -2548G > A and Q223R polymorphisms
      in the LEP and LEPR genes, respectively. 303 obese cases (101 men and 202 women)
      and 606 controls (202 men and 404 women) were selected from a Spanish
      Mediterranean population. Genetic, clinical and life-style characteristics were
      analyzed. No association was found between the -2548G > A polymorphism and
      obesity. However, the Q223R variant was significantly associated with obesity in
      a recessive model, the RR genotype being more prevalent in controls than in obese
      subjects. The inverse association between the Q223R polymorphism and obesity (OR
      = 0.62; 95% CI: 0.39-0.99) remained significant even after additional adjustment
      for education, tobacco smoking, alcohol, physical activity, origin of the obese
      patient, and the -2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32
      0.89). In conclusion, the -2548G > A polymorphism is not a relevant obesity
      marker in this Mediterranean population, although Q223R does seen to be so.

PMID- 17031519
TI  - Incidence of bacterial and viral enteric pathogens in children with
      gastroenteritis over a one year-period, in Attica, Greece.

PMID- 17031520
TI  - Epidemiological and virological features of HBV infection in HIV-2 infected
      patients living in southeastern France.
AB  - We studied HBV infection in 34 HIV-2-infected patients followed-up in Marseilles.
      Ten (29%) patients were chronically-infected with HBV, which represents a three
      times higher rate than in HIV-1-infected patients in Europe. HBV occult infection
      was diagnosed in two patients. HBV genotype E was found in seven patients; its
      specificities and the reciprocal influence of HIV-2/HBV-co-infection remain to be
      evaluated.

PMID- 17031521
TI  - The biobank of the Norwegian Mother and Child Cohort Study: a resource for the
      next 100 years.
AB  - INTRODUCTION: Long-term storage of biological materials is a critical component
      of any epidemiological study. In designing specimen repositories, efforts need to
      balance future needs for samples with logistical constraints necessary to process
      and store samples in a timely fashion. OBJECTIVES: In the Norwegian Mother and
      Child Cohort Study (MoBa), the Biobank was charged with long-term storage of more
      than 380,000 biological samples from pregnant women, their partners and their
      children for up to 100 years. METHODS: Biological specimens include whole blood,
      plasma, DNA and urine; samples are collected at 50 hospitals in Norway. All
      samples are sent via ordinary mail to the Biobank in Oslo where the samples are
      registered, aliquoted and DNA extracted. DNA is stored at -20 degrees C while
      whole blood, urine and plasma are stored at -80 degrees C. RESULTS: As of July
      2006, over 227,000 sample sets have been collected, processed and stored at the
      Biobank. Currently 250-300 sets are received daily. An important part of the
      Biobank is the quality control program. CONCLUSION: With the unique combination
      of biological specimens and questionnaire data, the MoBa Study will constitute a
      resource for many future investigations of the separate and combined effects of
      genetic, environmental factors on pregnancy outcome and on human morbidity,
      mortality and health in general.

PMID- 17031522
TI  - Quantitative immunogold study of increased expression of metallothionein-I/II in
      the brain perivascular areas of diabetic scrapie-infected mice.
AB  - Quantitative immunogold procedure was used to study the distribution of
      metallothionein I/II (MT-I/II) at the ultrastructural level in the perivascular
      areas, including microvascular endothelial cells (ECs) and astrocytes with their
      perivascular end-feet, in brains of scrapie-infected hyperglycemic (diabetic) and
      normoglycemic (non-diabetic) mice. Samples of the fronto-parietal cortex obtained
      from diabetic and non-diabetic scrapie-infected, as well as from non-infected
      (control) SJL/J mice, were processed for immunocytochemical examination. In
      control mice, the labelling of the ECs was of low intensity, restricted to few
      immunogold particles in the cytoplasm. More intense labelling was present in the
      cytoplasm of astrocytic perivascular processes and perikarya, where it was
      associated with endoplasmic reticulum and fibrils. A few immunosignals were also
      present inside the nuclei of astrocytes. In diabetic mice the labelling of the EC
      cytoplasm was slightly increased, whereas in the cytoplasm of perivascular
      processes and pericarya of astrocytes, including their nuclei, there was
      significant enhancement of labelling. In these cells the density of immunosignals
      was highest in the areas of cytoplasm containing bundles of fibrils. In non
      diabetic, scrapie-infected mice the intensity of immunolabelling was higher than
      in control mice but slightly lower than in diabetic mice. These results are
      similar to those in Alzheimer's disease reported by other authors, and suggest
      that neurodegenerative diseases as well as metabolic stress enhance the
      metallothionein expression in perivascular regions of brain cerebral cortex,
      predominantly in astrocytes.

PMID- 17031523
TI  - Coxsackievirus and adenovirus receptor expression in non-malignant lung tissues
      and clinical lung cancers.
AB  - Adenoviral vector mediated gene delivery has been applied in clinical trials and
      mechanistic studies to explore new treatment approaches for lung cancers. The
      expression of coxsackievirus adenovirus receptor (CAR), the primary receptor for
      the most commonly used adenovirus serotype 5 (Ad5)-based vectors, predominantly
      determines the permissiveness of lung cancer cells. CAR expression is also
      suggested to modulate tumor cell proliferation capacity. Here, we studied CAR
      expression in archival lung cancer specimens by using well-characterized CAR 72
      antibodies. High levels of CAR expression were observed in most of the 32 cases
      of squamous cell carcinoma lung cancers and in all the five cases of small cell
      lung cancers investigated. In contrast, high levels of CAR expression were
      detected only in 6 of 22 adenocarcinoma lung cancers. The relative levels of CAR
      expression did not correlate with the pathologic grade in lung cancers, and was
      thus inconsistent with a role of modulating cancer cell proliferation. Of note,
      CAR expression was not detected in non-malignant alveolar cells. Our data suggest
      a preferred utility of Ad5 vector mediated gene delivery to squamous cell
      carcinoma lung cancers, small cell lung cancers, but not to the majority of
      adenocarcinoma lung cancers.

PMID- 17031524
TI  - NMR assignment of the C-terminal domain of Ole e 9, a major allergen from the
      olive tree pollen.

PMID- 17031525
TI  - 1H, 13C and 15N resonance assignments of the VAP-A: OSBP complex.

PMID- 17031526
TI  - Resonance assignments of a CoA binding protein from Klebsiella pneumoniae.

PMID- 17031527
TI  - 1H, 13C and 15N resonance assignments of the catalytic domain of the goldfish
      RICH protein.

PMID- 17031528
TI  - A nomenclature and data model to describe NMR experiments.
AB  - Despite ongoing efforts in organising NMR information, there is no consistent and
      well-described generic standard for naming NMR experiments. The main reason for
      the absence of a universal naming system is that the information content of the
      coherence pathways is difficult to describe in full detail. We propose a system
      that describes the common and generic elements of the coherence pathways produced
      by pulse sequences. The system itself is formalised by an 'NMR experiment
      protocol' model, which is described in the Universal Modelling Language (UML) as
      part of the CCPN data model. Furthermore, normalized experiment names can be
      derived from this proposed model. We hope this article will stimulate discussion
      to organise the wealth of NMR experiments, and that by bringing this discussion
      into the public domain we can improve and expand our proposed system to include
      as much information and as many NMR experiments as possible.

PMID- 17031529
TI  - Random sampling of evolution time space and Fourier transform processing.
AB  - Application of Fourier Transform for processing 3D NMR spectra with random
      sampling of evolution time space is presented. The 2D FT is calculated for pairs
      of frequencies, instead of conventional sequence of one-dimensional transforms.
      Signal to noise ratios and linewidths for different random distributions were
      investigated by simulations and experiments. The experimental examples include 3D
      HNCA, HNCACB and (15)N-edited NOESY-HSQC spectra of (13)C (15)N labeled ubiquitin
      sample. Obtained results revealed general applicability of proposed method and
      the significant improvement of resolution in comparison with conventional spectra
      recorded in the same time.

PMID- 17031530
TI  - Spectral editing: selection of methyl groups in multidimensional solid-state
      magic-angle spinning NMR.
AB  - A simple spectroscopic filtering technique is presented that may aid the
      assignment of (13)C and (15)N resonances of methyl-containing amino-acids in
      solid-state magic-angle spinning (MAS) NMR. A filtering block that selects methyl
      resonances is introduced in two-dimensional (2D) (13)C-homonuclear and (15)N
      (13)C heteronuclear correlation experiments. The 2D (13)C-(13)C correlation
      spectra are recorded with the methyl filter implemented prior to a (13)C-(13)C
      mixing step. It is shown that these methyl-filtered (13)C-homonuclear correlation
      spectra are instrumental in the assignment of C(delta) resonances of leucines by
      suppression of C(gamma)-C(delta) cross peaks. Further, a methyl filter is
      implemented prior to a (15)N-(13)C transferred-echo double resonance (TEDOR)
      exchange scheme to obtain 2D (15)N-(13)C heteronuclear correlation spectra. These
      experiments provide correlations between methyl groups and backbone amides. Some
      of the observed sequential (15)N-(13)C correlations form the basis for initial
      sequence-specific assignments of backbone signals of the outer-membrane protein
      G.

PMID- 17031531
TI  - In-cell NMR spectroscopy of proteins inside Xenopus laevis oocytes.
AB  - In-cell NMR is an application of solution NMR that enables the investigation of
      protein conformations inside living cells. We have measured in-cell NMR spectra
      in oocytes from the African clawed frog Xenopus laevis. (15)N-labeled ubiquitin,
      its derivatives and calmodulin were injected into Xenopus oocytes and two
      dimensional (1)H-(15)N correlation spectra of the proteins were obtained. While
      the spectrum of wild-type ubiquitin in oocytes had rather fewer cross-peaks
      compared to its in vitro spectrum, ubiquitin derivatives that are presumably
      unable to bind to ubiquitin-interacting proteins gave a markedly larger number of
      cross-peaks. This observation suggests that protein-protein interactions between
      ubiquitin and ubiquitin-interacting proteins may cause NMR signal broadening, and
      hence spoil the quality of the in-cell HSQC spectra. In addition, we observed the
      maturation of ubiquitin precursor derivative in living oocytes using the in-cell
      NMR technique. This process was partly inhibited by pre-addition of ubiquitin
      aldehyde, a specific inhibitor for ubiquitin C-terminal hydrolase (UCH). Our work
      demonstrates the potential usefulness of in-cell NMR with Xenopus oocytes for the
      investigation of protein conformations and functions under intracellular
      environmental conditions.

PMID- 17031532
TI  - Interrogating the druggable genome with structural informatics.
AB  - Structural genomics projects are producing protein structure data at an
      unprecedented rate. In this paper, we present the Target Informatics Platform
      (TIP), a novel structural informatics approach for amplifying the rapidly
      expanding body of experimental protein structure information to enhance the
      discovery and optimization of small molecule protein modulators on a genomic
      scale. In TIP, existing experimental structure information is augmented using a
      homology modeling approach, and binding sites across multiple target families are
      compared using a clique detection algorithm. We report here a detailed analysis
      of the structural coverage for the set of druggable human targets, highlighting
      drug target families where the level of structural knowledge is currently quite
      high, as well as those areas where structural knowledge is sparse. Furthermore,
      we demonstrate the utility of TIP's intra- and inter-family binding site
      similarity analysis using a series of retrospective case studies. Our analysis
      underscores the utility of a structural informatics infrastructure for extracting
      drug discovery-relevant information from structural data, aiding researchers in
      the identification of lead discovery and optimization opportunities as well as
      potential "off-target" liabilities.

PMID- 17031533
TI  - Cheminformatics analysis and learning in a data pipelining environment.
AB  - Workflow technology is being increasingly applied in discovery information to
      organize and analyze data. SciTegic's Pipeline Pilot is a chemically intelligent
      implementation of a workflow technology known as data pipelining. It allows
      scientists to construct and execute workflows using components that encapsulate
      many cheminformatics based algorithms. In this paper we review SciTegic's
      methodology for molecular fingerprints, molecular similarity, molecular
      clustering, maximal common subgraph search and Bayesian learning. Case studies
      are described showing the application of these methods to the analysis of
      discovery data such as chemical series and high throughput screening results. The
      paper demonstrates that the methods are well suited to a wide variety of tasks
      such as building and applying predictive models of screening data, identifying
      molecules for lead optimization and the organization of molecules into families
      with structural commonality.

PMID- 17031534
TI  - SVM approach for predicting LogP.
AB  - The logarithm of the partition coefficient between n-octanol and water (logP) is
      an important parameter for drug discovery. Based upon the comparison of several
      prediction logP models, i.e. Support Vector Machines (SVM), Partial Least Squares
      (PLS) and Multiple Linear Regression (MLR), the authors reported SVM model is the
      best one in this paper.

PMID- 17031535
TI  - Reverse fingerprinting, similarity searching by group fusion and fingerprint bit
      importance.
AB  - Recent research has shown that using data fusion rules in fingerprint-based
      similarity searching can improve results over traditional searches. Group fusion
      scores, which use multiple reference compounds, have in particular been shown to
      be quite effective in increasing enrichment rates over single reference structure
      based searches. In this paper, the effectiveness of using data fusion with
      multiple reference compounds to increase similarity search recall rates was
      investigated using 44 biological targets and four different 2D fingerprinting
      systems, including a new 2D typed triangle fingerprinting system introduced here.
      Scaffold-hopping abilities using data fusion rules were investigated using eight
      (8) different classes of scaffolds active against cGMP phosphodiesterase isoform
      5 (PDE5). An approach to using the reference group for ranking and visualizing
      important fingerprints bits, or reverse fingerprinting, was presented, and used
      to score and visualize important pharmacophore features within sample active
      molecules. Finally, similarity statistics within the reference groups were
      investigated and compared to recall rates.

PMID- 17031536
TI  - JEDA: Joint entropy diversity analysis. An information-theoretic method for
      choosing diverse and representative subsets from combinatorial libraries.
AB  - The joint entropy-based diversity analysis (JEDA) program is a new method of
      selecting representative subsets of compounds from combinatorial libraries.
      Similar to other cell-based diversity analyses, a set of chemical descriptors is
      used to partition the chemical space of a library of compounds; however, unlike
      other metrics for choosing a compound from each partition, a Shannon-entropy
      based scoring function implemented in a probabilistic search algorithm determines
      a representative subset of compounds. This approach enables the selection of
      compounds that are not only diverse but that also represent the densities of
      chemical space occupied by the original chemical library. Additionally, JEDA
      permits the user to define the size of the subset that the chemist wishes to
      create so that restrictions on time and chemical reagents can be considered.
      Subsets created from a chemical library by JEDA are compared to subsets obtained
      using other partition-based diversity analyses, namely principal components
      analysis and median partitioning, on a combinatorial library derived from the
      Comprehensive Medical Chemistry Dataset.

PMID- 17031537
TI  - Differences in hepatotoxicity and gene expression profiles by anti-diabetic PPAR
      gamma agonists on rat primary hepatocytes and human HepG2 cells.
AB  - Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) are a
      new class of oral drugs designed to treat insulin-resistant diabetes (i.e., type
      2 diabetes). However, troglitazone, the first compound in the class approved by
      the US Food and Drug Administration (FDA) in 1997 was found to be hepatotoxic and
      was withdrawn from the market after reports of severe liver failure. The
      mechanism of PPAR gamma agonist-induced hepatotoxicity remains unknown. In this
      study, we examined the hepatotoxic effects of five PPAR gamma agonists
      (ciglitazone, pioglitazone, rosiglitazone, troglitazone, and JTT-501) on rat
      primary hepatocytes and human HepG2 cells. We also compared the gene expression
      profiles of rat primary hepatocytes after exposure to PPAR gamma agonists by
      using the Rat Genome Survey Microarray system from Applied Biosystems in order to
      understand the mechanisms of hepatotoxicities induced by PPARgamma agonists.
      Consistent with the hepatotoxicity data, our results demonstrate that the gene
      expression profiles affected by troglitazone and ciglitazone can be clearly
      distinguished from those by pioglitazone and rosiglitazone. Genes that are
      differentially expressed between the more toxic troglitazone/ciglitazone group
      and the less toxic rosiglitazone/pioglitazone group are involved in necrotic,
      apoptotic, and cell proliferative pathways. The five compounds were also
      clustered based on a set of molecular descriptors. The clustering based on
      chemical structural information is in good agreement with the clustering of
      compounds based on cytotoxicity or gene expression data, indicating a strong
      relationship between chemical structure and biological endpoints. Our work
      suggests that microarray analysis together with toxicological observations can be
      used to rank drugs for hepatotoxicity and to evaluate the safety of new
      compounds.

PMID- 17031538
TI  - Application of linear discriminant analysis in the virtual screening of
      antichagasic drugs through trypanothione reductase inhibition.
AB  - We have performed virtual screening to identify new lead trypanothione reductase
      inhibitor (TRI) compounds, enzyme present in Tripanozoma cruzi, the agent
      responsible of Chagas disease. From a training set of 58 compounds, linear
      discriminant analysis (LDA) was performed using 2D and 3D descriptors as
      discriminating variables in order to find out which function of descriptors
      characterizes the active TRI. The values of the statistical parameters F-
      Snedecor and Wilk's lambda for the discriminant function (DF) showed good
      statistical significance, as long as the rate of success in the prediction for
      both the training and the test set: 91.38% and 88.63%, in that order. Internal
      validation through the Leave--Group--Out methodology was performed with good
      results, assuring the stability of the DF. Afterwards, the DF was applied in
      virtual screening of 422,367 compounds. The optimum range of values of octanol-
      water partition coefficient for a compound to develop trypanothione reductase
      inhibition was applied as a second filtering criteria. 739 structurally
      heterogeneous drugs of the virtual library were selected as promissory TRI.

PMID- 17031539
TI  - Leadlikeness and structural diversity of synthetic screening libraries.
AB  - High program failure rates in the pharmaceutical industry have prompted the
      development of predictive software that can profile compound libraries as being
      'druglike' (resembling existing drugs) and/or 'leadlike' (possessing the
      structural and physicochemical profile of a quality lead). In recent years, these
      two notions prompted pharmaceutical companies to clean up their corporate
      libraries of screening compounds. In order to maintain and expand the size and
      diversity of these corporate libraries, pharmaceutical companies still continue
      to add compounds to these, mainly by the acquisition of screening libraries. In
      this paper, we have analyzed 45 commercially available libraries, offered by
      suppliers of screening chemistry, for leadlikeness and diversity of the offered
      structures. To this end we have used a set of structural and physicochemical
      filters for leadlikeness that was developed in-house. These 45 supplier libraries
      contained a total of 5.3 million structures, of which 49% (2,592,778 structures)
      turned out to be unique, and only 12% (677,328 structures) were found to be both
      unique and leadlike. A diversity analysis revealed that big differences exist
      between the various offered libraries.

PMID- 17031540
TI  - Managing, profiling and analyzing a library of 2.6 million compounds gathered
      from 32 chemical providers.
AB  - The data for 3.8 million compounds from structural databases of 32 providers were
      gathered and stored in a single chemical database. Duplicates are removed using
      the IUPAC International Chemical Identifier. After this, 2.6 million compounds
      remain. Each database and the final one were studied in term of uniqueness,
      diversity, frameworks, 'drug-like' and 'lead-like' properties. This study also
      shows that there are more than 87 000 frameworks in the database. It contains 2.1
      million 'drug-like' molecules among which, more than one million are 'lead-like'.
      This study has been carried out using 'ScreeningAssistant', a software dedicated
      to chemical databases management and screening sets generation. Compounds are
      stored in a MySQL database and all the operations on this database are carried
      out by Java code. The druglikeness and leadlikeness are estimated with 'in-house'
      scores using functions to estimate convenience to properties; unicity using the
      InChI code and diversity using molecular frameworks and fingerprints. The
      software has been conceived in order to facilitate the update of the database.
      'ScreeningAssistant' is freely available under the GPL license.

PMID- 17031541
TI  - Microwave assisted oxidation of some aromatics by hydrogen peroxide at supported
      tungsten catalyst.
AB  - The oxidation of some arenes with the alkyl side groups by means of hydrogen
      peroxide is been presented. As the activator of hydrogen peroxide tungstoboric
      acid was chosen. The catalyst was examined under both homogeneous and
      heterogeneous conditions. The reactions under conventional conditions were
      compared with the microwave assisted reactions.

PMID- 17031542
TI  - A novel workflow for the inverse QSPR problem using multiobjective optimization.
AB  - A workflow for the inverse quantitative structure-property relationship (QSPR)
      problem is reported in this paper for the de novo design of novel chemical
      entities (NCE) in silico through the application of existing QSPR models to
      calculate multiple objectives, including prediction confidence measures, to be
      optimized during the de novo design process. Two physical property datasets are
      applied as case studies of the inverse QSPR workflow (IQW): mean molecular
      polarizability and aqueous solubility. The case studies demonstrate the
      optimization of molecular structures to within a property range of interest; the
      optimized structures are then validated against QSPR models that are generated
      from sets of alternative descriptors to those used in the IQW. The paper
      concludes with a discussion of the results from the case studies.

PMID- 17031543
TI  - Ascorbate peroxidase-thioredoxin interaction.
AB  - Proteomics data have suggested ascorbate peroxidase (APX) to be a potential
      thioredoxin-interacting protein. Using recombinant enzymes, we observed that
      incubation of pea cytosolic APX with reduced poplar thioredoxins h drastically
      inactivated the peroxidase. A similar inactivation is induced by reduced
      glutathione and dithiothreitol, whereas diamide and oxidized glutathione have no
      effect. Oxygen consumption measurements, modifications of the APX visible
      spectrum and protection by hydrogen peroxide scavenging enzymes suggest that APX
      oxidizes thiols leading to the generation of thiyl radicals. These radicals can
      in turn react with thiyl anions to produce the disulfide radical anions, which
      are responsible for oxygen reduction and subsequent hydrogen peroxide production.
      The APX inactivation is not due solely to hydrogen peroxide since fluorimetry
      indicates that the environment of the APX tryptophan residues is dramatically
      modified only in the presence of thiol groups. The physiological implications of
      this interaction are discussed.

PMID- 17031544
TI  - Thioredoxin-dependent regulation of photosynthetic glyceraldehyde-3-phosphate
      dehydrogenase: autonomous vs. CP12-dependent mechanisms.
AB  - Regulation of the Calvin-Benson cycle under varying light/dark conditions is a
      common property of oxygenic photosynthetic organisms and photosynthetic
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the targets of this
      complex regulatory system. In cyanobacteria and most algae, photosynthetic GAPDH
      is a homotetramer of GapA subunits which do not contain regulatory domains. In
      these organisms, dark-inhibition of the Calvin-Benson cycle involves the
      formation of a kinetically inhibited supramolecular complex between GAPDH, the
      regulatory peptide CP12 and phosphoribulokinase. Conditions prevailing in the
      dark, i.e. oxidation of thioredoxins and low NADP(H)/NAD(H) ratio promote
      aggregation. Although this regulatory system has been inherited in higher plants,
      these phototrophs contain in addition a second type of GAPDH subunits (GapB)
      resulting from the fusion of GapA with the C-terminal half of CP12.
      Heterotetrameric A(2)B(2)-GAPDH constitutes the major photosynthetic GAPDH
      isoform of higher plants chloroplasts and coexists with CP12 and A(4)-GAPDH. GapB
      subunits of A(2)B(2)-GAPDH have inherited from CP12 a regulatory domain (CTE for
      C-terminal extension) which makes the enzyme sensitive to thioredoxins and
      pyridine nucleotides, resembling the GAPDH/CP12/PRK system. The two systems are
      similar in other respects: oxidizing conditions and low NADP(H)/NAD(H) ratios
      promote aggregation of A(2)B(2)-GAPDH into strongly inactivated A(8)B(8)-GAPDH
      hexadecamers, and both CP12 and CTE specifically affect the NADPH-dependent
      activity of GAPDH. The alternative, lower activity with NADH is always
      unaffected. Based on the crystal structure of spinach A(4)-GAPDH and the analysis
      of site-specific mutants, a model of the autonomous (CP12-independent) regulatory
      mechanism of A(2)B(2)-GAPDH is proposed. Both CP12 and CTE seem to regulate
      different photosynthetic GAPDH isoforms according to a common and ancient
      molecular mechanism.

PMID- 17031545
TI  - Plant methionine sulfoxide reductase A and B multigenic families.
AB  - Methionine oxidation to methionine sulfoxide (MetSo), which results in
      modification of activity and conformation for many proteins, is reversed by an
      enzyme present in most organisms and termed as methionine sulfoxide reductase
      (MSR). On the basis of substrate stereospecificity, two types of MSR, A and B,
      that do not share any sequence similarity, have been identified. In the present
      review, we first compare the multigenic MSR families in the three plant species
      for which the genome is fully sequenced: Arabidopsis thaliana, Oryza sativa, and
      Populus trichocarpa. The MSR gene content is larger in A. thaliana (five MSRAs
      and nine MSRBs) compared to P. trichocarpa (five MSRAs and four MSRBs) and O.
      sativa (four MSRAs and three MSRBs). A complete classification based on gene
      structure, sequence identity, position of conserved reactive cysteines and
      predicted subcellular localization is proposed. On the basis of in silico and
      experimental data originating mainly from Arabidopsis, we report that some MSR
      genes display organ-specific expression patterns and that those encoding
      plastidic MSRs are highly expressed in photosynthetic organs. We also show that
      the expression of numerous MSR genes is enhanced by environmental conditions
      known to generate oxidative stress. Thioredoxins (TRXs) constitute very likely
      physiological electron donors to plant MSR proteins for the catalysis of MetSO
      reduction, but the specificity between the numerous TRXs and methionine sulfoxide
      reductases (MSRs) present in plants remains to be investigated. The essential
      role of plant MSRs in protection against oxidative damage has been recently
      demonstrated on transgenic Arabidopsis plants modified in the content of
      cytosolic or plastidic MSRA.

PMID- 17031546
TI  - Evolution of redoxin genes in the green lineage.
AB  - The availability of the Arabidopsis genome revealed the complexity of the gene
      families implicated in dithiol disulfide exchanges. Most non-green organisms
      present less dithiol oxidoreductase genes. The availability of the almost
      complete genome sequence of rice now allows a systematic search for thioredoxins,
      glutaredoxins and their reducers. This shows that all redoxin families previously
      defined for Arabidopsis have members in the rice genome and that all the deduced
      rice redoxins fall within these families. This establishes that the redoxin
      classification applies both to dicots and monocots. Nevertheless, within each
      redoxin type the number of members is not the same in these two higher plants and
      it is not always possible to define orthologues between rice and Arabidopsis. The
      sequencing of two unicellular algae (Chlamydomonas and Ostreococcus) genomes are
      almost finished. This allowed us to follow the origin of the different gene
      families in the green lineage. It appears that most thioredoxin and glutaredoxin
      types, their chloroplastic, mitochondrial and cytosolic reducers are always
      present in these unicellular organisms. Nevertheless, striking differences appear
      in comparison to higher plant redoxins. Some thioredoxin types are not present in
      these algal genomes including thioredoxins o, clot and glutaredoxins CCxC.
      Numerous redoxins, including the cytosolic thioredoxins, do not fit with the
      corresponding higher plant classification. In addition both algae present a NADPH
      dependent thioredoxin reductase with a selenocysteine which is highly similar to
      the animal thioredoxin reductases, a type of thioredoxin reductase not present in
      higher plants.

PMID- 17031549
TI  - MitoK(ATP)-dependent changes in mitochondrial volume and in complex II activity
      during ischemic and pharmacological preconditioning of Langendorff-perfused rat
      heart.
AB  - It has been proposed that activation of the mitochondrial ATP-sensitive potassium
      channel (mitoK(ATP)) is part of signaling pathways triggering the
      cardioprotection afforded by ischemic preconditioning of the heart. This work was
      to analyze the mitochondrial function profile of Langendorff-perfused rat hearts
      during the different phases of various ischemia-reperfusion protocols.
      Specifically, skinned fibers of ischemic preconditioned hearts exhibit a decline
      in the succinate-supported respiration and complex II activity during ischemia,
      followed by a recovery during reperfusion. Meanwhile, the apparent affinity of
      respiration for ADP (which reflects the matrix volume expansion) is increased
      during preconditioning stimulus and, to a larger extent, during prolonged
      ischemia. This evolution pattern is mimicked by diazoxide and abolished by 5
      hydroxydecanoate. It is concluded that opening the mitoK(ATP) channel mediates
      the preservation of mitochondrial structure-function via a mitochondrial matrix
      shrinkage and a reversible inactivation of complex II during prolonged ischemic
      insult.

PMID- 17031550
TI  - Electrical stimulation of the energy metabolism in yeast cells using a planar Ti
      Au-electrode interface.
AB  - We report on the influence of dielectric pulse injection on the energy metabolism
      of yeast cells with a planar interdigitated electrode interface. The energy
      metabolism was measured via NADH fluorescence. The application of dielectric
      pulses results in a distinct decrease of the fluorescence, indicating a response
      of the energy metabolism of the yeast cells. The reduction of the NADH signal
      significantly depends on the pulse parameters, i.e., amplitude and width.
      Furthermore, the interface is used to detect electrical changes in the cell
      electrolyte system, arising from glucose-induced oscillations in yeast cells and
      yeast extract, by dielectric spectroscopy at 10 kHz. These dielectric
      investigations revealed a beta(1)-dispersion for the system electrolyte/yeast
      cells as well as for the system electrolyte/yeast extract. In agreement with
      control measurements we obtained a glycolytic period of 45 s for yeast cells and
      of 11 min for yeast extract.

PMID- 17031551
TI  - Painful languages of the body: experiences of headache among women in two
      Peruvian communities.
AB  - This exploratory study focuses on the understandings of and experiences with
      headache in two settings in Peru: the Quechua-speaking district of Ayacucho, in
      southern Peru, and a poor urban district of Lima Metropolitana. More
      specifically, it explores the personal and collective meanings constructed around
      women's headache experiences. Structured and open-ended interviews were
      administered to patients suffering headache to elicit interpretations of headache
      episodes. An analysis of the collected narratives suggests that headache is often
      comprehended in a polysemic framework, where meanings ascribed in bodily,
      emotional, family, and social terms articulate individual and shared notions of
      suffering within larger contexts of social dislocation. Often woven into
      experiences of solitude, headache accounts are lived and told in dynamic temporal
      spaces, and narrate dissolution of family ties and tensions associated with
      women's roles. The results underscore the significance of patients' subjective
      interpretations of painful experiences and underscore the connections between
      bodily and emotional pain and distress experienced at family, community, and
      larger social levels.

PMID- 17031552
TI  - Monitoring the effects of BCNU chemotherapy Wafers (Gliadel) in glioblastoma
      multiforme with proton magnetic resonance spectroscopic imaging at 3.0 Tesla.
AB  - Carmustine wafers (Gliadel Wafer) are implanted at resection in some patients
      with high-grade gliomas. Studies suggest that proton magnetic resonance
      spectroscopic imaging ((1)H MRSI) demonstrates early changes predictive of future
      failure or response to systemic chemotherapy. This study explores (1)H MRSI as a
      means to assess peri-tumoral tissue response post-resection and Gliadel((R))
      implantation in patients with high-grade gliomas. Pilot (1)H MRSI data are
      presented that demonstrate noninvasive, serial monitoring of metabolic changes at
      the tumor site following Gliadel implantation. Three patients with newly
      diagnosed glioblastoma multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla
      prior to resection and at 3-5 and > or =12 weeks post-operatively. Baseline MRS
      spectra of tumor tissue from all patients were characterized by marked increases
      of choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA),
      typical of GBM compared with normal contra-lateral brain tissue. Post
      operatively, spectra were analyzed from the resection cavity and peri-tumoral
      regions and compared with normal tissue from the contra-lateral brain at
      baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and CHO/NAA
      decreased compared to contra-lateral brain at 3-5 weeks compared with baseline
      following Gliadel therapy and surgery but prior to radiotherapy. This study
      indicates that (1)H MRSI has the ability to localize regions of heterogeneous
      response following Gliadel treatment. Although data are limited, these results
      suggest that metabolic indicators of outcome can be successfully monitored pre-
      and post-surgical resection and Gliadel implantation with (1)H MRSI. Additional
      study of patients receiving Gliadel Wafers using (1)H MRSI may serve to aid
      clinicians in assessing tumor regression and gauging efficacy of this
      chemotherapy treatment.

PMID- 17031553
TI  - Phase II study of thalidomide and radiation in children with newly diagnosed
      brain stem gliomas and glioblastoma multiforme.
AB  - A phase II study was conducted to assess the efficacy of administering daily
      thalidomide concomitantly with radiation and continuing for up to 1 year
      following radiation in children with brain stem gliomas (BSG) or glioblastoma
      multiforme (GBM). Secondary objectives were to obtain preliminary evidence of
      biologic activity of thalidomide and to evaluate toxicities from chronic
      administration of thalidomide in this population. Thirteen patients (2-14 years
      old) with newly diagnosed BSG (12 patients) or GBM (one patient) were enrolled
      between July 1999 and June 2000. All patients received focal radiotherapy to a
      total dose of 5,580 cGy. Thalidomide was administered once daily beginning on the
      first day of radiation and continued for 12 months or until the patient came off
      study. The starting dose was 12 mg/kg (rounded down to the nearest 50 mg) and was
      increased by 20% weekly, if tolerated, to 24 mg/kg or 1,000 mg (whichever was
      lower). Advanced imaging techniques and urine and serum analysis for anti
      angiogenic markers were performed in some patients in an attempt to correlate
      changes with clinical effect of therapy. No patients completed the planned 12
      months of thalidomide therapy and all have since died of disease progression. The
      median duration of therapy was 5 months (range 2-11 months). Nine patients came
      off study for progressive disease (PD), three patients due to toxicity and one
      patient withdrew consent. Several patients on this study required more extended
      courses of high dose steroids than would have been otherwise expected for this
      population due to significant peritumoral edema and necrosis. No consistent
      pattern emerged from the biologic correlative studies from 11 patients. However,
      advanced imaging with techniques such as MR spectroscopy, MR perfusion and 18
      fluorodeoxyglucose positron emission tomography (FDG-PET) were helpful in
      distinguishing growing tumor from treatment effect and necrosis in some patients.
      The median time to progression (TTP) was 5 months (range 2-11 months) and the
      median time to death (TTD) was 9 months (range 5-17 months). In this small
      patient sample adding thalidomide to radiation did not improve TTP or TTD from
      historical controls, however, toxicity appeared to be increased.

PMID- 17031554
TI  - Safety and efficacy of convection-enhanced delivery of ACNU, a hydrophilic
      nitrosourea, in intracranial brain tumor models.
AB  - Convection-enhanced delivery (CED) is a local infusion technique, which delivers
      chemotherapeutic agents directly to the central nervous system, circumventing the
      blood-brain barrier and reducing systemic side effects. CED distribution is
      significantly increased if the infusate is hydrophilic. This study evaluated the
      safety and efficacy of CED of nimustine hydrochloride: 3-[(4-amino-2-methyl-5
      pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), a
      hydrophilic nitrosourea, in rat 9 L: brain tumor models. The local neurotoxicity
      of ACNU delivered via CED was examined in normal rat brains, and the maximum
      tolerated dose (MTD) was estimated at 0.02 mg/rat. CED of ACNU at the MTD
      produced significantly longer survival time than systemic administration (P <
      0.05, log-rank test). Long-term survival (80 days) and eradication of the tumor
      occurred only in the CED-treated rats. The tissue concentration of ACNU was
      measured by high-performance liquid chromatography, which revealed that CED of
      ACNU at the dose of 100-fold less total drug than intravenous injection carried
      almost equivalent concentrations of ACNU into rat brain tissue. CED of
      hydrophilic ACNU is a promising strategy for treating brain tumors.

PMID- 17031555
TI  - Local intracerebral administration of O(6)-benzylguanine combined with systemic
      chemotherapy with temozolomide of a patient suffering from a recurrent
      glioblastoma.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a major
      determinant of methylating anticancer drug resistance. Inactivation of MGMT by
      pseudosubstrate inhibitors, such as O(6)-benzylguanine (O(6)BG), sensitizes tumor
      cells to O(6)-alkylating agents. However, systemic administration of O(6)BG
      causes depletion of MGMT in all tissues of the body. Therefore, dose reduction of
      O(6)-alkylating drugs administered together with O(6)BG is required in order to
      avoid unwished toxic side effects. To attenuate the increased systemic toxicity
      caused by MGMT inhibitors, local MGMT inactivation would be desirable. Here, we
      report on intracerebral treatment with O(6)BG of a patient suffering from
      glioblastoma. O(6)BG was administered weekly in the tumor cavity by means of an
      Ommaya reservoir. This application was well tolerated. Concomitant treatment with
      temozolomide (Temodal) was associated with transient tumor stabilization without
      detectable side effects. Although evidence is still lacking that local O(6)BG
      administration caused MGMT to be depleted in the residual tumor, the trial shows
      that intracerebral treatment with O(6)BG is feasible. It might be a safe strategy
      for improving glioma therapy by treatment with temozolomide (and presumably also
      other O(6)-alkylating drugs) concomitant with O(6)BG without augmenting drug
      induced systemic side effects.

PMID- 17031556
TI  - Anaplastic ependymoma with cartilaginous and osseous metaplasia: report of a rare
      case and review of literature.
AB  - Gliomas with cartilaginous metaplasia are extremely uncommon and thought to be
      due to metaplasia of the mesenchymal supportive elements. The tumors are located
      in the midline, mostly fourth ventricle and rarely in the pons. The present paper
      describes an unusual case of anaplastic ependymoma with cartilaginous and osseous
      metaplasia in a young boy which was located in the suprasellar, interpeduncular
      prepontine and left cerebello-pontine cistern. To the best of our knowledge, this
      cartilaginous metaplasia in ependymomas has been reported only thrice.

PMID- 17031557
TI  - Administration of temozolomide during and after radiotherapy for newly diagnosed
      high-grade gliomas excluding glioblastoma multiforme.
AB  - Primary brain high-grade gliomas, excluding glioblastoma are rare and
      heterogeneous tumors, showing different characteristic mutations and a better
      prognosis than glioblastomas. The addition of chemotherapy to the radiotherapy in
      the newly diagnosed disease has not been established yet. We treated 9 patients
      with newly diagnosed tumors with temozolomide at 75 mg/m2 for 7 days a week
      during standard radiotherapy, followed by six cycles at 200 mg/m2 on days 1-5
      every 28 days. Fluorescence in situ hybridization for the 1 p/19 q loss was
      performed in seven out of the 9 patients. With a median follow-up of 15 months
      (range, 8-50), eight patients are alive and one died from disease progression.
      Four patients had disease progression at 7, 15, 14 and 13 months from the
      diagnosis. The 1 p/19 q loss was found in 5 patients; three have no evidence of
      disease, one had partial disease remission and one disease progression.
      Toxicities included one discitis requiring treatment withdrawal and specific
      antibiotic therapy, and one transient grade 3 psoriasiform reaction. Based on
      this small series of patients, the addition of temozolomide to radiotherapy may
      be recommended.

PMID- 17031558
TI  - Survival and quality of life after hypofractionated stereotactic radiotherapy for
      recurrent malignant glioma.
AB  - PURPOSE: To prospectively evaluate efficacy, side effects and quality of life in
      patients with recurrent malignant glioma after hypofractionated stereotactic
      radiotherapy. METHODS AND MATERIALS: From 1/2003 to 8/2005, 15 patients with
      recurrent malignant glioma were prospectively scheduled for hfSRT with 5 x 7 Gy
      (90%-isodose). Median gross tumor volume and planning target volume were 5.75
      (range, 0.77-21.94) and 22.4 (range, 4.22-86.79) cc, respectively. Irradiation
      was performed with the dedicated stereotactic radiosurgery system Novalistrade
      mark (BrainLAB, Heimstetten, Germany). RESULTS: Rates of remission, no change and
      progressive disease were 27%, 33%, and 40%, respectively, after a median follow
      up of 9 months. Progression-free survival rates at 6 and 12 months were 75% and
      53% respectively. Quality of life, measured by the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire scores could be
      kept stable in two thirds of the patients for a median time of 9 months,
      respectively. CONCLUSION: Hypofractionated stereotactic radiotherapy with 5 x 7
      Gy of recurrent high grade glioma is an effective treatment that helps to
      maintain quality of life for an acceptable period, comparable to the results
      obtained with current chemotherapy schedules. Combined approaches of
      radiotherapy, chemotherapy and other targeted therapies deserve further
      inverstigation.

PMID- 17031559
TI  - PLXDC1 (TEM7) is identified in a genome-wide expression screen of glioblastoma
      endothelium.
AB  - Glioblastomas are a highly aggressive brain tumor, with one of the highest rates
      of new blood vessel formation. In this study we used a combined experimental and
      bioinformatics strategy to determine which genes were highly expressed and
      specific for glioblastoma endothelial cells (GBM-ECs), compared to gene
      expression in normal tissue and endothelium. Starting from fresh glioblastomas,
      several rounds of negative and positive selection were used to isolate GBM-ECs
      and extract total RNA. Using Serial Analysis of Gene Expression (SAGE), 116,259
      transcript tags (35,833 unique tags) were sequenced. From this expression
      analysis, we found 87 tags that were not expressed in normal brain. Further
      subtraction of normal endothelium, bone marrow, white blood cell and other normal
      tissue transcripts resulted in just three gene transcripts, ANAPC10,
      PLXDC1(TEM7), and CYP27B1, that are highly specific to GBM-ECs.
      Immunohistochemistry with an antibody for PLXDC1 showed protein expression in GBM
      microvasculature, but not in the normal brain endothelium tested. Our results
      suggest that this study succeeded in identifying GBM-EC specific genes. The
      entire gene expression profile for the GBM-ECs and other tissues used in this
      study are available at SAGE Genie (http://cgap.nci.nih.gov/SAGE). Functionally,
      the protein products of the three tags most specific to GBM-ECs have been
      implicated in processes critical to endothelial cell proliferation and
      differentiation, and are potential targets for anti-angiogenesis based therapy.

PMID- 17031560
TI  - Resveratrol inhibits cell growth and induces apoptosis of rat C6 glioma cells.
AB  - Resveratrol (Res) has been reported to inhibit tumor initiation, promotion, and
      progression in a variety of cell culture systems depending on the specific cell
      type and cellular environment. In the present study, we determined the effect of
      Res on the cell growth and apoptosis of rat glioma C6 cell line as well as mouse
      fibroblast 3T3 cell line, in vitro. Concurrently, we investigated whether caspase
      3 is involved in the Res-induced apoptosis of rat glioma cells. Exposure to Res
      exhibits a significant anti-proliferative effect and induces an increase in the
      population of apoptotic cells on C6 cells in a concentration- and time-dependent
      manner, but not for normal 3T3 fibroblast cells, as measured by methyl thiazolyl
      tetrazolium assay and flow cytometer. Distinguished increase of C6 cells in S
      phase is observed after the treatment of Res as compared to insignificant change
      in cell cycle distribution of 3T3 cells. TdT-mediated dUTP nick end labeling
      fluorescence staining, HE staining, and scanning electron microscope revealed
      abnormal morphology and ultrastructure in C6 cells treated with Res. Our data
      showed that Res can increase the expression and induced the activation of caspase
      3 in rat glioma C6 cells. These results suggest that Res has significant
      apoptosis-inducing effect on C6 glioma cells other than normal fibroblast 3T3
      cells in vitro and caspase-3 may act as a potential mediator in the process.

PMID- 17031561
TI  - A North American brain tumor consortium (NABTC 99-04) phase II trial of
      temozolomide plus thalidomide for recurrent glioblastoma multiforme.
AB  - BACKGROUND: Laboratory and clinical data suggest that the anti-angiogenic agent,
      thalidomide, if combined with cytotoxic agents, may be effective against
      recurrent glioblastoma multiforme (GBM). OBJECTIVES: To determine 6-month
      progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in
      adults with recurrent GBM. PATIENTS AND METHODS: Eligible patients had recurrent
      GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was
      given at 150-200 mg/m(2)/day on days 1-5 of each 28-day cycle. Thalidomide was
      given orally at 400 mg at bedtime (days 1-28) and increased to 1,200 mg as
      tolerated. Patients were evaluated with magnetic resonance imaging scans every 56
      days. The study was designed to detect an increase of the historical 6PFS for GBM
      from 10 to 30%. RESULTS: Forty-four patients were enrolled, 43 were evaluable for
      efficacy and safety. The study population included 15 women, 29 men; median age
      was 53 years (range 32-84); median Karnofsky performance status was 80% (range 60
      100%). Thirty-six (82%) patients were chemotherapy-naive. There were 57 reports
      of toxicity of grade 3 or greater. Non-fatal grade 3-4 granulocytopenia occurred
      in 15 patients (34%). The objective response rate was 7%. The estimated
      probability of being progression-free at 6 months with this therapy is 24% [95%
      confidence interval (C.I.) 12-38%]. The median time to progression is 15 weeks
      (95% C.I. 10-20 weeks). There was no observed correlation between serum levels of
      vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and
      the 6PFS outcome. CONCLUSION: This drug combination was reasonably safe, but with
      little indication of improvement compared to temozolomide alone.

PMID- 17031562
TI  - EGF genetic polymorphism is associated with clinical features but not malignant
      phenotype in neurofibromatosis type 1 patients.
AB  - Neurofibromatosis type 1 (NF1) is characterized by a wide variation in clinical
      presentation and in some cases progression to malignant tumor. Epidermal growth
      factor (EGF) is an important mitogen for Schwann cells and is involved in the
      development of malignant tumors in NF1 patients. We hypothesized that EGF +61 G/A
      functional polymorphism, which represents constitutional all-life exposure to
      higher EGF expression and circulating levels, may predispose for precocious and
      more aggressive manifestations of disease. We found that clinical findings of
      intestinal polyps are significantly more frequent in patients with G homozygous
      genotype (P = 0.023). Those carriers of GG genotype have earlier onset of cafe-au
      lait spots and Lisch nodules appearance (P = 0.030 and P = 0.017, respectively).
      Nevertheless, the EGF overexpressing genotype-GG, is not associated with higher
      risk for malignant progression or severity of disease. EGF polymorphism may play
      a role in the earlier onset of NF1 pigment cell-related manifestations and in
      intestinal polyps' development. Further studies in larger samples should confirm
      the absence of risk for having higher severity grade or malignant phenotype in
      NF1 patients.

PMID- 17031563
TI  - A case report and review of the literature.
AB  - Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare central nervous
      system neoplasm in which gliomatous tissue is diffusely identified in the
      subarachnoid space with no evidence of a primary intraparenchymal tumor. A 52
      year-old man presented low back pain followed by sudden unconsciousness and had
      also cognitive dysfunction and meningeal sign. Examinations of cerebrospinal
      fluid (CSF) did not show malignant cells but increased protein and pleocytosis.
      Magnetic resonance (MR) imaging demonstrated diffuse leptomeningeal enhancement
      without any source of intraparenchymal lesion. Fluid-attenuated inversion
      recovery (FLAIR) also demonstrated individual diffuse high intensity area in the
      subarachnoid space. A biopsy disclosed wide spreading of anaplastic glial cells
      within the leptomeninges. He died 3 months later because of disease progression
      despite both radiotherapy and chemotherapy. Post-mortem examination identified
      PDLG and several neuropathological features of glioblastoma as well. Reviewing
      previous cases of PDLG instructs that this entity is rare, resembles meningitis
      in clinical pictures, usually occurs in a relatively younger population and has
      more progressive clinical course than the ordinary form of malignant gliomas.

PMID- 17031564
TI  - The role of citrullinated proteins suggests a novel mechanism in the pathogenesis
      of multiple sclerosis.
AB  - The pathogenesis of MS is unknown. In our studies, we have demonstrated an
      important role for citrullinated myelin basic protein (MBP). The accompanying
      loss of positive charge compromises the ability of MBP to interact with the lipid
      bilayer. The conversion of arginine to citrulline in brain is carried out by an
      enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was
      increased in MS normal-appearing white matter. The mechanism responsible for this
      increase involved hypomethylation of the promoter region in the PAD 2 gene in MS,
      but no change (compared to normal) was found in thymus tissue DNA from the same
      MS patients. In addition, no change was observed in other neurological diseases,
      including Alzheimer's, Parkinson's, and Huntington's. We propose that
      citrullinated MBP, resulting from elevated levels of PAD 2 represents an
      important biochemical pathway in the pathogenesis of MS.

PMID- 17031565
TI  - Dopamine reduction of GABA currents in striatal medium-sized spiny neurons is
      mediated principally by the D(1) receptor subtype.
AB  - Dopamine modulates voltage- and ligand-gated currents in striatal medium-sized
      neurons (MSNs) through the activation of D1- and D2-like family receptors.
      GABA(A) receptor-mediated currents are reduced by D1 receptor agonists, but the
      relative contribution of D(1) or D(5 )receptors in this attenuation has been
      elusive due to the lack of selective pharmacological agents. Here we examined
      GABA(A) receptor-mediated currents and the effects of D1 agonists on MSNs from
      wildtype and D(1) or D(5 )receptor knockout (KO) mice. Immunohistochemical and
      single-cell RT-PCR studies demonstrated a lack of compensatory effects after
      genetic deletion of D(1) or D(5) receptors. However, the expression of GABA(A
      )receptor alpha1 subunits was reduced in D(5) KO mice. At the functional level,
      whole-cell patch clamp recordings in dissociated MSNs showed that GABA peak
      current amplitudes were smaller in cells from D(5) KO mice indicating that lack
      of this receptor subtype directly affected GABA(A)-mediated currents. In striatal
      slices, addition of a D1 agonist reduced GABA currents significantly more in D(5)
      KO compared to D(1) KO mice. We conclude that D(1) receptors are the main D1-like
      receptor subtype involved in the modulation of GABA currents and that D(5)
      receptors contribute to the normal expression of these currents in the striatum.

PMID- 17031567
TI  - Assessment of respondent driven sampling for recruiting female sex workers in two
      Vietnamese cities: reaching the unseen sex worker.
AB  - Respondent driven sampling (RDS) is a relatively new method to sample hard-to
      reach populations. Until this study, female sex workers (FSWs) in Vietnam were
      sampled using a variety of methods, including time location sampling (TLS), which
      may not access the more hidden types of FSWs. This paper presents an analysis
      from an HIV biological and behavioral surveillance survey to assess the
      feasibility and effectiveness of RDS to sample FSWs, to determine if RDS can
      reach otherwise inaccessible FSWs in Vietnam and to compare RDS findings of HIV
      risk factors with a theoretical TLS. Through face-to-face interviews with FSWs in
      Ho Chi Minh City (HCMC) and Hai Phong (HP), data were collected about the venues
      where they most often solicit their clients. These data were used to create three
      variables to assess whether FSWs solicit their clients in locations that are
      visible, semi-visible and non-visible. For this analysis, the visible group
      simulates a sample captured using TLS. Survey results in HIV prevalence and
      related risk factors and service utilization, adjusted for sampling methodology,
      were compared across each of the three FSW visibility groups to assess potential
      bias in TLS relative to RDS. The number of self-reported visible FSWs (HCMC:
      n=311; HP: n=162) was much larger than those of the semi-visible (HCMC: n=65; HP:
      n=43) and non-visible (HCMC: n=37; HP: n=10) FSWs in HCMC and HP. Non-visible
      FSWs in both cities were just as likely as visible and semi-visible FSWs to be
      HIV positive (HCMC: visible 14.5%, semi-visible 13.8%, non-visible 13.5%, p value
      = 0.982; HP: visible 35.2%, semi-visible 30.2%, non-visible 30.0%, p value =
      0.801), to practice behaviors that put them at risk for contracting and
      transmitting HIV (injecting drug use-HCMC: visible 13.8%, semi-visible 12.3%, non
      visible 5.4%, p value = 0.347; HP: visible 38.9%, semi-visible 23.3%, non-visible
      30.0%, p value = 0.378, to have no condom use in the past month -HCMC only:
      visible 52.7%, semi-visible 63.1%, non-visible 48.6%, p value = 0.249) and to
      have symptoms of a sexually transmitted infection (STI) in the past year (HCMC:
      visible 16.1%, semi-visible 12.3%, non-visible 16.2%, p value = 0.742; HP:
      visible 13.6%, semi-visible 18.6%, non-visible 20.0%, p value = 0.640). There was
      a difference found among the visible, semi-visible and non-visible groups in HP
      for no past month condom use (visible 53.1%, semi-visible 79.1%, non-visible
      60.0%, p value = 0.009). This study found that RDS was successful at recruiting
      hidden types of FSWs in Vietnam. Past reports of FSWs in Vietnam have assessed
      the more visible FSWs as being the most vulnerable and at risk for HIV. Although
      the number of visible FSWs is much higher than those of the semi and non-visible
      groups, this study found that the non-visible FSWs are very vulnerable to HIV
      infection. If prevention programs are targeting and responding to those who are
      most likely to be assessed (e.g., more visible types of FSWs) then this analysis
      indicates that a significant proportion of the FSW population at risk for HIV may
      not be receiving optimal HIV information and services.

PMID- 17031566
TI  - White matter rafting--membrane microdomains in myelin.
AB  - The myelin membrane comprises a plethora of regions that are compositionally,
      ultrastructurally, and functionally distinct. Biochemical dissection of
      oligodendrocytes, Schwann cells, and central and peripheral nervous system myelin
      by means such as cold-detergent extraction and differential fractionation has led
      to the identification of a variety of detergent-resistant membrane assemblies,
      some of which represent putative signalling platforms. We review here the
      different microdomains that have hitherto been identified in the myelin membrane,
      particularly lipid rafts, caveolae, and cellular junctions such as the tight
      junctions that are found in the radial component of the CNS myelin sheath.

PMID- 17031569
TI  - Flow cytometry sorting protocol of Bacillus spore using ultraviolet laser and
      autofluorescence as main sorting criterion.
AB  - The ultraviolet (UV) Fluorescent Aerodynamic Particle Sizer (FLAPS), a flow
      cytometer-like apparatus was developed by the Canadian Department of National
      Defence for real-time detection of autofluorescence of biological aerosol
      particles such as bacterial spores. The direct relation between autofluorescence
      intensity and viability has recently been reported and viable spore are more
      autofluorescent in UV (Laflamme, Frontiers in Bioscience). The goal of this
      manuscript is to describe a flow cytometry sorting protocol based on UV-induced
      autofluorescence. An EPICS ELITE ESP flow cytometer equipped with a UV laser and
      cell sorter was used to mimic the optical properties of FLAPS and to study the
      two extremes of a spore population according to its autofluorescence (lower level
      of autofluorescence (LLA) and higher level of autofluorescence (HLA) spores).
      Bacillus subtilis var niger was used as a surrogate for Bacillus anthracis spores
      and sorted using autofluorescence intensity as the main criterion. The protocol
      developed in our laboratory to sort Bacillus spores according to their
      autofluorescence properties is described. Purity of each sorted population was
      greater than 95%. Using autofluorescence as the main criterion, we demonstrate
      that it is possible to separate two distinct spore populations.

PMID- 17031570
TI  - Kinetic fluorimetric measurement of trace resorcinol in phenol mixtures.
AB  - A kinetic spectrofluorimetric method was studied to measure the concentration of
      trace resorcinol. The proposed method is based on the inhibitory effect of
      resorcinol on the oxidation of rhodamine B by potassium bromate in the medium of
      dilute sulfuric acid. The detection limit and linear range of the proposed
      resorcinol measurement method are 12 microg L(-1) and 24 approximately 280 microg
      L(-1), respectively. Relative standard derivations of eleven measurements for 80
      microg L(-1) and 200 microg L(-1) resorcinol solutions are 2.12% and 1.08%,
      respectively. The trace of resorcinol can be determined directly by the proposed
      method without any pre-separation process when phenol and many other phenolic
      compounds are present.

PMID- 17031568
TI  - The development of a standardized neighborhood deprivation index.
AB  - Census data are widely used for assessing neighborhood socioeconomic context.
      Research using census data has been inconsistent in variable choice and usually
      limited to single geographic areas. This paper seeks to a) outline a process for
      developing a neighborhood deprivation index using principal components analysis
      and b) demonstrate an example of its utility for identifying contextual variables
      that are associated with perinatal health outcomes across diverse geographic
      areas. Year 2000 U.S. Census and vital records birth data (1998-2001) were merged
      at the census tract level for 19 cities (located in three states) and five
      suburban counties (located in three states), which were used to create eight
      study areas within four states. Census variables representing five socio
      demographic domains previously associated with health outcomes, including
      income/poverty, education, employment, housing, and occupation, were empirically
      summarized using principal components analysis. The resulting first principal
      component, hereafter referred to as neighborhood deprivation, accounted for 51 to
      73% of the total variability across eight study areas. Component loadings were
      consistent both within and across study areas (0.2-0.4), suggesting that each
      variable contributes approximately equally to "deprivation" across diverse
      geographies. The deprivation index was associated with the unadjusted prevalence
      of preterm birth and low birth weight for white non-Hispanic and to a lesser
      extent for black non-Hispanic women across the eight sites. The high correlations
      between census variables, the inherent multidimensionality of constructs like
      neighborhood deprivation, and the observed associations with birth outcomes
      suggest the utility of using a deprivation, index for research into neighborhood
      effects on adverse birth outcomes.

PMID- 17031571
TI  - Fluorescence of styryl dyes-DNA complexes induced by single- and two-photon
      excitation.
AB  - The series of novel monomer and homodimer styryl dyes based on (p
      dimethylaminostyryl) benzothiazolium residues were synthesized and studied as
      possible fluorescent probes for nucleic acids detection. Spectral-luminescent and
      spectral-photometric properties of obtained dyes in the unbound state and in DNA
      presence were studied. Fluorescence emission induced by two-photon excitation of
      dye-DNA complexes in aqueous buffer solution was registered. Two-photon
      absorption cross section values of the studied dyes in DNA presence were
      evaluated.

PMID- 17031572
TI  - Rotational diffusion and solvatochromic correlation of coumarin 6 laser dye.
AB  - Rotational diffusion of coumarin 6 (C6) laser dye has been examined in n-decane
      and methanol as a function of temperature. The rotational reorientation of this
      probe has been measured in these solvents. It is observed that the decrease in
      viscosity of the solution is responsible for the decrease in the rotational
      relaxation time of the probe molecule. The molecule C6 has long reorientation
      times in n-decane solvent as compared to methanol over all temperatures. It is
      found that the coumarin 6 rotates slower in n-decane than in methanol especially
      at higher values of viscosity over temperature. Two methods are chosen to
      determine the ground state and excited state dipole moments. The change in dipole
      moments is estimated from Bakhshiev-Chamma-Viallet equations and, the ground and
      excited state dipole moments from Kawski et al. equations, by using the
      variations of the Stokes shifts with the dielectric constant and refractive index
      of the solvent. Our results are quite reliable which are solvatochromic
      correlation obtained using solvent polarity functions. The reported results show
      that excited state dipole moment is greater than ground state dipole moment,
      which indicates that the excited state is more polar than the ground state.

PMID- 17031573
TI  - Time-resolved FRET and FLIM of four-way DNA junctions.
AB  - Conformational transitions in a 4-way DNA junction when titrated with ionic
      solutions are studied using time-resolved fluorescence resonance energy transfer.
      Parameters characterising the transition in terms of critical ion concentration
      (c1/2) and the Hill coefficient for ion binding are obtained by fitting a simple
      two-state model using steady-state spectra. Data obtained from a fluorescence
      lifetime plate reader and analysed by fitting a single exponential to donor
      fluorescence lifetime decays are shown to be in good agreement with the
      parameters obtained from steady-state measurements. Fluorescence lifetimes,
      however, offer advantages, particularly in being independent of fluorophore
      concentration, output intensity, inhomogeneity in the excitation source and
      output wavelength. We demonstrate preliminary FRET-FLIM images of DNA junction
      solutions obtained using a picosecond gated CCD which are in agreement with
      results from a fluorescence lifetime plate reader. The results suggest that time
      resolved FRET-FLIM is sensitive to subtle structural changes and may be useful in
      assays based on 4-way DNA junctions.

PMID- 17031574
TI  - Ruby crystal for demonstrating time- and frequency-domain methods of fluorescence
      lifetime measurements.
AB  - We present experiments that are convenient and educational for measuring
      fluorescence lifetimes with both time- and frequency-domain methods. The sample
      is ruby crystal, which has a lifetime of about 3.5 milliseconds, and is easy to
      use as a class-room demonstration. The experiments and methods of data analysis
      are used in the lab section of a class on optical spectroscopy, where we go
      through the theory and applications of fluorescence. Because the fluorescence
      decay time of ruby is in the millisecond region, the instrumentation for this
      experiment can be constructed easily and inexpensively compared to the nanosecond
      resolved instrumentation required for most fluorescent compounds, which have
      nanosecond fluorescence lifetimes. The methods are applicable to other
      luminescent compounds with decay constants from microseconds and longer, such as
      transition metal and lanthanide complexes and phosphorescent samples. The
      experiments, which clearly demonstrate the theory and methods of measuring
      temporally resolved fluorescence, are instructive and demonstrate what the
      students have learned in the lectures without the distraction of highly
      sophisticated instrumentation.

PMID- 17031575
TI  - Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53
      and NF-kappaB in human tongue carcinoma : BLCAP overexpression induces S phase
      arrest and apoptosis.
AB  - Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor
      suppressor gene identified from the human bladder carcinoma. Our previous studies
      have shown that BLCAP overexpression could inhibit cell growth by inducing
      apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor Biol 27: 221
      226, 2006]. Such evidence suggests the alterations in BLCAP may play an important
      role in tumorigenesis. To further study the biological function of the BLCAP
      gene, we constructed a recombinant retroviral vector encoding BLCAP cDNA.
      Overexpressed BLCAP, via stable infection of exogenous BLCAP, resulted in growth
      inhibition of the human tongue cancer cell line Tca8113 in vitro, accompanied by
      S phase cell cycle arrest and apoptosis. The growth inhibition was correlated
      with up-regulation of p21(WAF1/CIP1 )expression and down-regulation of Bcl-XL and
      Bcl-2 expressions. However, p53 expression and NF-kappaB activity remained
      unchanged post infection. Furthermore, no changes in p53 phosphorylation at Ser46
      and nuclear localization, which are critical to p53 function, were observed in
      BLCAP-overexpressed cells. Taken together, BLCAP may play a role not only in
      regulating cell proliferation but also in coordinating apoptosis and cell cycle
      via a novel way independent of p53 and NF-kappaB.

PMID- 17031576
TI  - Antiatherogenic and radioprotective role of folic acid in whole body gamma
      irradiated mice.
AB  - Free radical mediated oxidative damage is one of the prime factors for
      atherogenic changes in humans. We have shown that the folic acid administration
      reduced the risk of the atherogenic factors induced by gamma-radiation. Folic
      acid administration prevented the radiation induced increase in the plasma
      lipoprotein lipase activity and also prevented the radiation-induced increase in
      the hepatic cholesterol and triglycerides levels. These results indicate the role
      of folic acid as an antiatherogenic agent. Further, we also report the
      radioprotective property of folic acid as demonstrated by reduction in the
      radiation induced membrane damage as measured by lipid peroxidation products and
      DNA damage, which was measured by alkaline comet assay.

PMID- 17031577
TI  - MMP-2 and MMP-9 activity is regulated by estradiol and tamoxifen in cultured
      human breast cancer cells.
AB  - Sex steroids play a dominant role in breast carcinogenesis by still largely
      unknown mechanisms. Matrix metalloproteinases (MMPs) have been extensively
      studied in the context of matrix biology but it is not known if sex steroids
      affect MMPs in breast cancer. MMPs degrade extracellular matrix components
      enabling tumor cell invasion and metastasis, but may also regulate the
      bioavailability of a variety of biologically active molecules such as anti
      angiogenic fragments, which may be beneficial for the host. This study shows that
      estradiol and tamoxifen regulate MMP-2 and MMP-9 as well as TIMP-1 and TIMP-2 in
      ER + PR + human breast cancer cells. The main finding was a significant effect of
      tamoxifen exposure, which increased intracellular and secreted protein levels
      whereas estradiol induced a significant decrease. The overall net effect of these
      alterations resulted in increased MMP-2/MMP-9 activity by tamoxifen treatment,
      which also significantly increased extracellular endostatin levels. We conclude
      that estradiol and tamoxifen have the ability to modulate MMP-2/MMP-9 activity,
      and endostatin levels in human breast cancer in vitro. The results suggest a
      possible role of MMP modulation associated with a generation of anti-angiogenic
      fragments in the therapeutic effect of tamoxifen in breast cancer.

PMID- 17031578
TI  - Factors in the delayed HIV presentation of immigrants in Northern California:
      implications for voluntary counseling and testing programs.
AB  - To describe the determinants of delayed HIV presentation in one Northern
      California County, the authors identify persons with an opportunistic infection
      (OI) at HIV diagnosis. From 2000-2002, a sample of HIV patients attending a
      public AIDS program (n=391) were identified. Immigrants composed 24% of our
      sample; 78.7% of immigrants were Hispanic. Immigrants, compared to U.S.-born
      patients, presented with lower initial CD4+ counts at diagnosis than U.S.-born
      patients (287 cells/mm(3) vs. 333 cells/mm(3), p=0.143), were more likely to have
      an OI at HIV diagnosis (29.8% vs. 17.2%, p=0.009), and were more likely to be
      hospitalized at HIV diagnosis (20.2% vs. 12.5%, p=0.064). We found only immigrant
      status was significantly and independently associated with delayed presentation.
      Interviews with 20 newly HIV diagnosed Hispanic patients suggest lack of
      knowledge regarding HIV risk, social stigma, secrecy and symptom driven health
      seeking behavior all contribute to delayed clinical presentation. The main
      precipitants of HIV testing for immigrants were HIV/AIDS related symptoms and
      sexually transmitted infection (STI)/HIV diagnosis in a sexual partner. These
      results support augmentation of STI/HIV voluntary clinical testing and partner
      notification services along the Mexico-California migrant corridor.

PMID- 17031579
TI  - Lengthier cryoablation and a bonus cryoapplication is associated with improved
      efficacy for cryothermal catheter ablation of supraventricular tachycardias in
      children.
AB  - INTRODUCTION: Cryoablation is an effective treatment for children with
      supraventricular tachycardias (SVT). The present study documents the effect of
      two different cryoablation protocols on acute and chronic success rates. METHODS
      AND RESULTS: Fifty-three consecutive patients (age range, 5-20 years) were
      treated; patients 1 to 17 were treated by a standard ablation protocol and
      patients 18 to 53 were treated by a modified ablation protocol that required
      lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate
      the acutely successful irreversible lesion created at intervention.
      Electrophysiological study (EPS) was performed with diagnostic catheters and
      cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath
      Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re
      entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or
      during isoproterenol performed 30 min post procedure, as well as non-inducibility
      and conduction block over the accessory pathway (AP). The chronic endpoint was
      arrhythmia recurrence post intervention. No permanent cryo-related complications
      or adverse outcomes were reported. Acute success rates for patients 1 to 17 and
      18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients
      without arrhythmia recurrence at 12 month follow-up was significantly different
      at 73 and 90%, respectively. CONCLUSIONS: Lengthier cryoablation delivery,
      approximating 7 min per cryoablation, increases the acute success rate at
      intervention. Moreover, these lengthier cryoablation deliveries plus a bonus
      cryoapplication to consolidate the acutely successful irreversible lesion created
      at intervention may also significantly improve the chronic success rate, while
      also maintaining an excellent safety profile for cryoablation treatment of
      children with SVT such as AVNRT and AP located near the AV junction.

PMID- 17031580
TI  - Electrical and hemodynamic function produced by stimulation of atropine sensitive
      right ventricular nerves in humans.
AB  - In mammalian ventricles including humans, it is recognized that parasympathetic
      ganglia innervate the heart. Little is known about the location and function of
      right ventricular parasympathetic nerves in humans. We hypothesized that in
      humans: (1) there are parasympathetic ganglia that supply the right ventricle
      that can be stimulated via an endocardial catheter and (2) stimulation of these
      fibers will alter the electrical and hemodynamic function of the right ventricle.
      Parasympathetic nerve stimulation was performed via an endocardial catheter
      placed along several sites of the right ventricle, superior vena cava, and right
      internal jugular area in humans. The spatial extent of parasympathetic
      innervation was mapped in 1-cm zones across the right ventricle. Cardiac output,
      heart rate, and atrioventricular conduction were monitored to provide independent
      assessment of parasympathetic innervation. In all 22 patients, ventricular
      refractoriness shortened from 12 +/- 3 to 3 +/- 1 ms during parasympathetic nerve
      stimulation, and the greatest shortening of refractoriness was observed at the
      base of the right ventricle (p = 0.01). No significant shortening in ventricular
      refractoriness occurred in areas beyond 2 cm from the right ventricular base.
      These results were compared by using T table test. The parasympathetic nerve
      stimulation protocol decreased cardiac output, reaffirming the principle effect
      of parasympathetic ganglia. Atropine was administered in seven patients. All
      effects from nerve stimulation were abolished after atropine administration.
      These results were also compared by using T table test. These data provide the
      first demonstration of the electrical and hemodynamic function by stimulation of
      atropine sensitive nerves of the human right ventricle. Greater understanding of
      parasympathetic innervation may lead to novel therapies for arrhythmias.

PMID- 17031581
TI  - Child care health consultation programs: barriers and recommendations.
AB  - OBJECTIVES: While many studies describe the need for health services in early
      care and education (ECE) settings and the role of child care health consultants
      (CCHCs), little information exists about the challenges to developing health
      consultation programs. The goal of this paper is to provide insight for the
      development of current and future child care health consultation programs by
      describing the barriers identified by CCHCs related to program implementation in
      20 California counties. METHODS: Forty-four child care health consultants
      participated in nine focus groups during their health consultation training at
      the California Training Institute. Participants were asked to discuss the
      barriers they encountered while establishing new county-wide child care health
      consultation programs. Themes were assigned to each response, and frequency and
      percentage of each theme were documented and trends were identified. RESULTS: The
      four general themes describing barriers to program implementation were: Program
      Management, Child Care Culture, Geography and Community Services. Twenty
      additional sub-themes, including Multi-agency involvement, Chaos, Travel time,
      and Fragmentation, were assigned to each response. The most frequent general
      theme was Program Management. The most frequent sub-theme was Professional
      Support. CONCLUSIONS: The barriers identified by the child care health
      consultants can be valuable for administrators and clinicians establishing or
      developing child care health consultation programs. Program managers should be
      prepared for the unique challenges of child care health consultation and provide
      flexibility and support for child care health consultants.

PMID- 17031582
TI  - Increasing access to program information: a strategy for improving adolescent
      health.
AB  - OBJECTIVES: To identify existing programs serving 11- to 15-year-olds that aim to
      improve adolescent health in the areas of Health & Well-being, Fitness, Family &
      Peer Relationships, School Environment, Smoking, Alcohol Use, and Violence and to
      assess the utility of readily available resources in providing detailed program
      information. METHODS: In Phase 1, publicly available program databases were
      searched to identify potential programs serving the target population. In Phase
      2, an in-depth search of a limited sample of programs meeting the content and age
      criteria was performed to identify program descriptors. RESULTS: Over 1,000
      program names were identified in Phase 1. Information regarding programs is
      becoming more readily available through the internet; however, the program
      information that was publicly available only begins to draw the picture. Phase 2
      revealed that a broad array of efforts are underway in all seven content areas,
      but found information on the program descriptors to be limited. CONCLUSIONS:
      Investment in programming is not enough; an upfront investment in communication
      and information sharing is critical in order to maximize the resources dedicated
      to the improvement of adolescent health. A well-publicized centralized program
      repository offered in conjunction with technical assistance would provide an
      efficient mechanism for this information sharing. We further suggest that the
      inherent gap between research and practice can be lessened by building a new body
      of practice knowledge. This would require improved program data collection by
      programs, the incorporation of program participation information in national
      surveys and enhanced evaluation efforts.

PMID- 17031583
TI  - Dyspareunia, urinary sensory symptoms, and incontinence among young Chinese
      women.
AB  - This study examined the prevalence of dyspareunia, urinary sensory symptoms, and
      urinary incontinence and explored their associations among sexually active
      Chinese women aged 15-34 years. Data from 3,150 women were analyzed from a survey
      undertaken during 2003 in 30 counties in China as part of the United Nations
      Population Fund Country Program. The overall prevalence of dyspareunia was 4.7%.
      Urinary pain, burning or frequency was reported by 8.5%, 6.2% reported urinary
      incontinence, and 2.3% reported both sets of urinary symptoms. The prevalence of
      urinary incontinence, both alone and in combination with sensory symptoms,
      increased in a linear manner with age. Dyspareunia was associated with early
      sexual debut, primary level of education, and membership of minority ethnic
      communities. Urinary sensory symptoms and incontinence were more common among
      those reporting early sexual debut, those with less schooling, and women engaged
      in agricultural and manual unskilled occupations. Urinary incontinence was more
      common among women who had had a previous vaginal delivery compared to
      nulliparous women. Dyspareunia was strongly associated with the presence of
      urinary symptoms, particularly among those with both sensory symptoms and
      incontinence (26.8%). Nearly a quarter of women who had dyspareunia had sought
      treatment but fewer had done so for urinary incontinence. Dyspareunia and urinary
      symptoms show distinct but overlapping patterns of association with demographic
      variables. The findings indicate unmet need for assessment and advice about these
      symptoms in women's reproductive health programs.

PMID- 17031585
TI  - Detection of differential viewing patterns to erotic and non-erotic stimuli using
      eye-tracking methodology.
AB  - As a first step in the investigation of the role of visual attention in the
      processing of erotic stimuli, eye-tracking methodology was employed to measure
      eye movements during erotic scene presentation. Because eye-tracking is a novel
      methodology in sexuality research, we attempted to determine whether the eye
      tracker could detect differences (should they exist) in visual attention to
      erotic and non-erotic scenes. A total of 20 men and 20 women were presented with
      a series of erotic and non-erotic images and tracked their eye movements during
      image presentation. Comparisons between erotic and non-erotic image groups showed
      significant differences on two of three dependent measures of visual attention
      (number of fixations and total time) in both men and women. As hypothesized,
      there was a significant Stimulus x Scene Region interaction, indicating that
      participants visually attended to the body more in the erotic stimuli than in the
      non-erotic stimuli, as evidenced by a greater number of fixations and longer
      total time devoted to that region. These findings provide support for the
      application of eye-tracking methodology as a measure of visual attentional
      capture in sexuality research. Future applications of this methodology to expand
      our knowledge of the role of cognition in sexuality are suggested.

PMID- 17031586
TI  - Psychometric properties of the Turkish version of the internalized homophobia
      scale.
AB  - The current study examined the psychometric properties of the Turkish version of
      the Internalized Homophobia Scale (IHS; Herek, Cogan, Gillis, & Glunt, 1997) in
      gay men living in Turkey. Participants were 132 men in romantic, intimate, or
      sexual relationships with men, and they identified themselves as homosexual
      (n=112) or bisexual (n=20). Alpha and split-half reliability coefficients
      revealed good internal consistency of the scale. Consistent with the original
      scale, the construct validity revealed a single factor for the scale. Regarding
      convergent validity, the IHS had significant correlations with psychological
      problems, particularly with symptoms of depression and anxiety; the scale also
      had a significant positive correlation with negative affect and a negative
      correlation with self-esteem. Regarding discriminant validity, the IHS had very
      low correlations with positive affect and hostility attitudes. The association
      between internalized homophobia and psychological problems remained significant
      even after controlling for the variance explained by self-esteem, negative
      affect, and positive affect. Hence, the psychometric properties of the Turkish
      version of IHS appear quite promising.

PMID- 17031588
TI  - Obesity, body image, and unsafe sex in men who have sex with men.
AB  - Little is known about the relationship among body weight, body image, and
      HIV/AIDS sexual risk behaviors. We examined this issue in a midwestern U.S.
      metropolitan area community sample of 316 men who have sex with men, a group at
      relatively high risk for HIV/AIDS. All data were self-reported by questionnaire
      using standard items to assess current body image, height and weight, and
      HIV/AIDS sexual risk behaviors. Logistic regression models were used to estimate
      cross-sectional associations. Forty-nine (15%) of the 316 men were classified as
      obese, and 56 (18%) had unsafe sex in the past three months. Normal weight or
      overweight men were 3.6 times more likely than obese men to have had unsafe sex,
      after adjusting for differences in body image and age. Men with better body image
      were 1.4 times more likely than men with lower body image to have had anal sex,
      after adjusting for differences in body weight and age. Non-obese men were no
      more or less likely than were obese men to have engaged in anal sex or in any sex
      in the past three months. This is the first study showing a positive relationship
      between below-obese body weight and unsafe sex and between better body image and
      anal sex in men who have sex with men. Future research should investigate these
      novel findings, perhaps using other study designs and data collection tools with
      less measurement error. Advances in knowledge about HIV/AIDS risk factors,
      including body weight and body image, could potentially contribute to more
      effective approaches to reducing this risk.

PMID- 17031589
TI  - Painful sexual intercourse caused by a disproportionately long penis: an
      historical note on a remarkable treatment devised by Guilhelmius Fabricius
      Hildanus (1560-1634).
AB  - Between 1598 and 1641, the famous surgeon Guilhelmius Fabricius Hildanus (1560
      1634) published 600 medical and surgical observations in his Observationum et
      curationum chirurgicarum centuriae I-VI. One of the case reports bears the title
      'Pain and infertility caused by a too large penis.' The woman described in this
      case report most likely suffered from positional deep dyspareunia. Hildanus
      invented in 1593 a remarkable made-to-measure device. This device was a very well
      considered and faultless curative for the woman's dyspareunia. It seemed that the
      dyspareunia had a simple cause: the disproportional large penis of the woman's
      husband. Four hundred years later, Hildanus' forgotten penis shortening device
      deserves a resurrection in today's medical practice. This remarkable and almost
      forgotten case report is described and discussed.

PMID- 17031590
TI  - Assessment of sexual functioning, mental health, and life goals in women with
      vaginal agenesis.
AB  - Vaginal agenesis is a congenital disorder defined by the incomplete formation of
      the vagina and other reproductive organs, often including the cervix, uterus, and
      fallopian tubes. For the patient, this frequently means infertility and an
      underdeveloped vagina with the subsequent difficulty to have vaginal intercourse.
      The patient with vaginal agenesis and her family then encounter a variety of
      psychological concerns that must be addressed during diagnosis, including
      weighing treatment options, managing interventions, and coping with long-term
      issues following diagnosis and treatment, such as partnership concerns and
      infertility. In this study, seven patients between the ages of 18 and 34
      completed questionnaires assessing demographic information, sexual functioning,
      mental health, self-esteem, and life goals. Sexual functioning results were
      highly variable. Participants reported significant emotional reactions at
      diagnosis as well as anxiety about the disorder, specifically its role in
      relationships. However, overall, the group showed average levels of mental health
      and self-esteem. Participants also showed positive coping techniques through
      conceptualization of life goals.

PMID- 17031591
TI  - Psychological symptomatology among Palestinian male and female adolescents living
      under political violence 2004-2005.
AB  - The aim of the study was to investigate gender differences in relation to
      exposure to domestic violence, political violence, family relations and
      psychological symptomatology in Palestinian adolescents. The sample consisted of
      1766 adolescents, males (54.1%) and females (45.9%), residents of West Bank
      cities subjected to violent political conflict. Participants completed a self
      report questionnaire consisting of the following measures: demographic variables,
      domestic violence, political violence events, the McMaster Family Assessment
      Device, and the Brief Symptom Inventory (BSI) psychological symptomatology.
      Results indicated that whereas there was no significant difference in the level
      of exposure to political violence between boys and girls, female adolescents
      exhibited higher levels of psychological symptoms compared to their male
      counterparts. Girls also reported higher levels of exposure to domestic violence
      and lower levels of family function than boys.

PMID- 17031592
TI  - Autonomous reovirus strain classification using filament-coupled antibodies.
AB  - We previously described a filament-based antibody recognition assay (FARA) that
      generates ELISA-like sandwich structures immobilized on a filament. FARA allows
      the coupling of antibodies to precise locations along a filament, on-line
      fluorescence detection of captured pathogen, and feedback-directed filament
      motion. These properties suggest that this approach might be useful as an
      automated means to rapidly classify unknown pathogens. In this report, we
      describe validation of the novel decision tree aspect of this technology using
      mammalian reovirus. Based on available antibodies, we developed a decision tree
      algorithm to detect virus with increasing specificity at each level of the tree.
      Using three strains of reovirus and a bacteriophage control, our system correctly
      classified the reovirus strains at a concentration of 2 x 10(12) virions ml(-1)
      and M13K07 phage at 3 x 10(11) virions ml(-1). Classification of reovirus strain
      type 3 Dearing (T3D) required three levels of testing: general reovirus
      classification in level 1, serotype 3 classification in level 2, and final T3D
      strain classification in level 3. Strain T3SA + also required three levels of
      testing before a final classification was returned in level 3. Classification of
      strain type 1 Lang (T1L) required two levels of testing. M13K07 phage detection
      required only one level of testing for classification. These results indicate
      that automated pathogen classification using FARA is feasible. Furthermore, the
      simplicity of the design could be exploited for development of more complex sub
      classification networks with additional levels and branches.

PMID- 17031593
TI  - Evaluation of important treatment parameters in supraphysiological thermal
      therapy of human liver cancer HepG2 cells.
AB  - This study was aimed at simulating the effect of various treatment parameters
      like heating rate (HR), peak temperature (PT) and hold/total treatment time on
      the viability of human liver cancer HepG2 cells subjected to different thermal
      therapy conditions. The problem was approached by investigating the injury
      kinetics obtained using experimentally measured viability of the cells, heated to
      temperatures of 50-70 degrees C for 0-9 min at HRs of 100, 200, 300 and 525
      degrees C min(-1). An empirical expression obtained between the activation energy
      (E) and HR was extended to obtain the E values over a broad range of HRs from 5
      to 600 degrees C min(-1) that mimic the actual conditions encountered in a
      typical thermal therapy protocol. Further, the effect of the HR (5-600 degrees C
      min(-1)) and PT (50-85 degrees C) on the cell survival was studied over a range
      of hold times. A significant drop in survival from 90% to 0% with the
      simultaneous increase in HR and PT was observed as the hold time increased from 0
      to 5 min. For complete cell death, the hold time increased with the increase in
      the HR for a given PT, while the total time showed presence of minima for 60, 65
      and 70 degrees C at HRs of 50, 100 and 200 degrees C min(-1), respectively.

PMID- 17031594
TI  - Optimisation of biochemical condition and substrates in vitro for tissue
      engineering of ligament.
AB  - In this work, we analysed the effect of growth factors on in vitro cell
      proliferation and collagens synthesis by fibroblasts cultured for 72 h on
      different substrates (silicon sheet with or without 1% gelatin, and glass as
      control surface) for ligament tissue engineering. A human fibroblast cell line
      (CRL-2703) was used. The synthesis of type I and type III collagens were
      evaluated qualitatively and quantitatively by RT-PCR and confocal microscopy,
      respectively. Cell proliferation was evaluated by two methods: (1) MTT assay (2)
      cell cycle analysis. It was found that PDGF-AB stimulate the proliferation of
      fibroblast cultured on gelatin coated silicon sheet in dose dependant manner with
      a maximum effect at 10 ng ml(-1). The exogenous TGF-beta1 induced the expression
      of type I and type III collagens in a dose and substrate-dependant manner. We
      deduce from this work that biochemical conditions and substrates have an
      important impact for optimisation of the tissue neo synthesis.

PMID- 17031595
TI  - NFAT and NFkappaB activation in T lymphocytes: a model of differential activation
      of gene expression.
AB  - Mathematical models for the regulation of the Ca(2+)-dependent transcription
      factors NFAT and NFkappaB that are involved in the activation of the immune and
      inflammatory responses in T lymphocytes have been developed. These pathways are
      important targets for drugs, which act as powerful immunosuppressants by
      suppressing activation of NFAT and NFkappaB in T cells. The models simulate
      activation and deactivation over physiological concentrations of Ca(2+), diacyl
      glycerol (DAG), and PKCtheta using single and periodic step increases. The model
      suggests the following: (1) the activation NFAT does not occur at low frequencies
      as NFAT requires calcineurin activated by Ca(2+) to remain dephosphorylated and
      in the nucleus; (2) NFkappaB is activated at lower Ca(2+) oscillation frequencies
      than NFAT as IkappaB is degraded in response to elevations in Ca(2+) allowing
      free NFkappaB to translocate into the nucleus; and (3) the degradation of IkappaB
      is essential for efficient translocation of NFkappaB to the nucleus. Through
      sensitivity analysis, the model also suggests that the largest controlling factor
      for NFAT activation is the dissociation/reassociation rate of the
      NFAT:calcineurin complex and the translocation rate of the complex into the
      nucleus and for NFkappaB is the degradation/resynthesis rate of IkappaB and the
      import rate of IkappaB into the nucleus.

PMID- 17031596
TI  - Proteoglycan breakdown of meniscal explants following dynamic compression using a
      novel bioreactor.
AB  - Motivated by our interest in examining meniscal mechanotransduction processes, we
      report on the validation of a new tissue engineering bioreactor. This paper
      describes the design and performance capabilities of a tissue engineering
      bioreactor for cyclic compression of meniscal explants. We showed that the system
      maintains a tissue culture environment equivalent to that provided by
      conventional incubators and that its strain output was uniform and reproducible.
      The system incorporates a linear actuator and load cell aligned together in a
      frame that is contained within an incubator and allows for large loads and small
      displacements. A plunger with six Teflon-filled Delrin compression rods is
      attached to the actuator compressing up to six tissue explants simultaneously and
      with even pressure. The bioreactor system was used to study proteoglycan (PG)
      breakdown in porcine meniscal explants following various input loading tests (0
      20% strain, 0-0.1 MPa). The greatest PG breakdown was measured following 20%
      compressive strain. These strain and stress levels have been shown to correspond
      to partial meniscectomy. Thus, these data suggest that removing 30-60% of
      meniscal tissue will result in the breakdown of meniscal tissue proteoglycans.

PMID- 17031597
TI  - Single-step 3-d image reconstruction in magnetic induction tomography:
      theoretical limits of spatial resolution and contrast to noise ratio.
AB  - Magnetic induction tomography (MIT) is a low-resolution imaging modality for
      reconstructing the changes of the complex conductivity in an object. MIT is based
      on determining the perturbation of an alternating magnetic field, which is
      coupled from several excitation coils to the object. The conductivity
      distribution is reconstructed from the corresponding voltage changes induced in
      several receiver coils. Potential medical applications comprise the continuous,
      non-invasive monitoring of tissue alterations which are reflected in the change
      of the conductivity, e.g. edema, ventilation disorders, wound healing and
      ischemic processes. MIT requires the solution of an ill-posed inverse eddy
      current problem. A linearized version of this problem was solved for 16
      excitation coils and 32 receiver coils with a model of two spherical
      perturbations within a cylindrical phantom. The method was tested with simulated
      measurement data. Images were reconstructed with a regularized single-step Gauss
      Newton approach. Theoretical limits for spatial resolution and contrast/noise
      ratio were calculated and compared with the empirical results from a Monte-Carlo
      study. The conductivity perturbations inside a homogeneous cylinder were
      localized for a SNR between 44 and 64 dB. The results prove the feasibility of
      difference imaging with MIT and give some quantitative data on the limitations of
      the method.

PMID- 17031599
TI  - Three-dimensional numerical modeling and computational fluid dynamics simulations
      to analyze and improve oxygen availability in the AMC bioartificial liver.
AB  - A numerical model to investigate fluid flow and oxygen (O(2)) transport and
      consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to
      two representative micro models of the AMC-BAL with two different gas capillary
      patterns, each combined with two proposed hepatocyte distributions. Parameter
      studies were performed on each configuration to gain insight in fluid flow, shear
      stress distribution and oxygen availability in the AMC-BAL. We assessed the
      function of the internal oxygenator, the effect of changes in hepatocyte oxygen
      consumption parameters in time and the effect of the change from an experimental
      to a clinical setting. In addition, different methodologies were studied to
      improve cellular oxygen availability, i.e. external oxygenation of culture
      medium, culture medium flow rate, culture gas oxygen content (pO(2)) and the
      number of oxygenation capillaries. Standard operating conditions did not
      adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to
      maintain O(2) consumption at minimally 90% of maximal uptake rate. Cellular
      oxygen availability was optimized by increasing the number of gas capillaries and
      pO(2) of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and
      maximal shear stresses were low and not considered to be harmful. This
      information can be used to increase cellular efficiency and may ultimately lead
      to a more productive AMC-BAL.

PMID- 17031598
TI  - Bioactive hydrogel substrates: probing leukocyte receptor-ligand interactions in
      parallel plate flow chamber studies.
AB  - The binding of activated integrins on the surface of leukocytes facilitates the
      adhesion of leukocytes to vascular endothelium during inflammation. Interactions
      between selectins and their ligands mediate rolling, and are believed to play an
      important role in leukocyte adhesion, though the minimal recognition motif
      required for physiologic interactions is not known. We have developed a novel
      system using poly(ethylene glycol) (PEG) hydrogels modified with either integrin
      binding peptide sequences or the selectin ligand sialyl Lewis X (SLe(X)) within a
      parallel plate flow chamber to examine the dynamics of leukocyte adhesion to
      specific ligands. The adhesive peptide sequences arginine-glycine-aspartic acid
      serine (RGDS) and leucine-aspartic acid-valine (LDV) as well as sialyl Lewis X
      were bound to the surface of photopolymerized PEG diacrylate hydrogels.
      Leukocytes perfused over these gels in a parallel plate flow chamber at
      physiological shear rates demonstrate both rolling and firm adhesion, depending
      on the identity and concentration of ligand bound to the hydrogel substrate. This
      new system provides a unique polymer-based model for the study of interactions
      between leukocytes and endothelium as well as a platform to develop improved
      scaffolds for cardiovascular tissue engineering.

PMID- 17031600
TI  - An ex vivo study of the biological properties of porcine aortic valves in
      response to circumferential cyclic stretch.
AB  - Normal physiological mechanical forces cause constant tissue renewal in aortic
      valve leaflets (AVL) while altered mechanical forces incite changes in their
      structural and biological properties. The current study aims at characterizing
      the remodeling properties of AVL subjected to cyclic circumferential stretch in a
      sterile ex vivo bioreactor. The leaflets cultured were stretched at a maximum
      rate of 300%s(-1) corresponding to a 15% strain for 48 h. Collagen, sulfated
      glycosaminoglycan (sGAG), and elastin contents of the stretched, fresh, and
      statically incubated leaflets were measured. Cusp morphology and cell phenotype
      were also examined. AVLs exposed to cyclic stretch showed a significant increase
      in collagen content (p < 0.05) when compared to fresh and statically incubated
      AVLs. sGAG content was significantly reduced in the stretched AVLs (p < 0.05)
      when compared to the fresh leaflets and was comparable between stretched and
      statically incubated AVLs. There was no statistically significant change in
      elastin content in all the three groups of AVLs (p > 0.05). Native aortic valve
      morphology was well preserved in stretched leaflets. Immunohistochemistry and
      immunoblotting studies showed an increased expression of alpha-smooth muscle
      actin (alpha-SMA) in stretched leaflets while alpha-SMA expression was reduced in
      statically incubated AVLs when compared to the fresh leaflets. To conclude,
      circumferential cyclic stretch altered the extracellular matrix remodeling
      activity of valvular cells, and consequently the extracellular matrix composition
      of the AVLs. Most interestingly, the contractile and fibrotic phenotypic
      expression of valve interstitial cells was enhanced. These results show that
      circumferential cyclic stretch is a possible mediator for AVL remodeling
      activity.

PMID- 17031601
TI  - Tannin composition affects the oxidative activities of tree leaves.
AB  - We examined whether tannin composition plays an important role in explaining the
      oxidative activities of tree leaves of Acer saccharum (sugar maple) and Quercus
      rubra (red oak). Sugar maple leaves contained substantial amounts of
      ellagitannins, condensed tannins, and galloyl glucoses, whereas red oak leaves
      contained almost exclusively condensed tannins. Oxidative activities of the crude
      phenolics from both species, and the phenolic fractions from sugar maple, were
      measured with electron paramagnetic resonance (EPR) spectrometry and UV-visible
      spectrophotometry. The two assays produced similar results: (1) sugar maple
      phenolics produced larger semiquinone radical concentrations,and higher
      semiquinone decay rates and browning rates than did red oak phenolics; (2)
      ellagitannin levels were positively associated with the three measures of
      oxidative activity; and (3) condensed tannin and galloyl glucose levels were
      negatively associated with these measures. The negative relationship between
      condensed tannin levels and oxidative activity resulted from the antioxidant
      effects of condensed tannins on hydrolyzable tannins; several purified condensed
      tannins significantly decreased the concentrations of semiquinone radicals and
      browning rates of pedunculagin (an ellagitannin) and pentagalloyl glucose. As
      expected, whole-leaf extracts from sugar maple produced elevated levels of
      semiquinone radicals, but none were observed in red oak extracts when the two
      species were compared with an EPR time-course assay. We conclude that the
      oxidative activities of tree leaves may be affected by tannin composition, and
      that the prooxidant activity of ellagitannins may be decreased by co-occurring
      condensed tannins.

PMID- 17031602
TI  - Neuroscience in Africa.

PMID- 17031603
TI  - Physico-chemical changes in cladodes (nopalitos) from cultivated and wild cacti
      (Opuntia spp.).
AB  - Physico-chemical and nutritional composition from four different nopalitos (young
      cladodes from cacti): Blanco sin Espinas, Blanco con Espinas, Verde Valtierrilla
      (cultivated materials) and a wild material from the central region of Mexico were
      studied at different sizes of harvesting. The first three are commercial crops.
      None of the tested materials exhibited superior characteristics in all of the
      evaluated parameters in relation to each one of them. In various cases properties
      of the wild crop were comparable, if not superior, to commercial ones. Some
      important changes were observed in total soluble solids, water content, texture,
      acidity and pH as affected by size of cladode and specific crop. Most cladode
      samples appear to be a good source of beta-carotene and lutein. The presence of
      these compounds is important for human nutraceutical purposes.

PMID- 17031604
TI  - Effect of DHA containing oils and powders on baking performance and quality of
      white pan bread.
AB  - Different sources of DHA and/or n-3 (omega-3) rich oils, oil emulsions and
      microencapsulated (ME) powders were tested at two different concentrations with
      the aim of producing fortified pan bread. Three oils (S-algae, fish and flax),
      two emulsified algae oils (Emulsion-P and Emulsion-L) and two ME oils (ME-S algae
      and ME-C algae) were compared. The DHA and n-3 oils replaced part of the
      shortening in order to obtain 32 g slices enriched with 25 or 50 mg DHA, 35 or 70
      mg total n-3 from fish oil and 90 or 180 mg linolenic from flax oil. Addition of
      oils did not significantly affect water absorption but reduced mix time whereas
      addition of the ME oils decreased both water absorption and mix time. Breads
      enriched with flax or ME-C oils had lower volume and higher density than the
      control, ME-S algae, Emulsion-P and Emulsion-L breads. All breads lost texture
      throughout 14 d storage, the major changes occurred after 3 d. The ME-S algae oil
      bread had the best softness after 14 d storage whereas breads produced from ME-S
      algae or ME-C algae oils had the poorest texture. Sensory evaluations indicated
      that the color of the ME-S algae oil fortified bread was significantly less
      preferred than the other loaves. After 6 d the control bread had higher
      acceptability compared with the rest of the breads enriched with high levels of
      DHA or omega-3 oils. The high-enriched fish oil bread was well accepted during
      the first days of storage but had the least preferred acceptability after 13 d.
      The best fortified breads were those supplemented with S-algae oil, Emulsion-P
      and Emulsion-L oils.

PMID- 17031605
TI  - Hypoglycemic and hypocholesterolemic effects of Coptis chinensis franch
      inflorescence.
AB  - Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch
      inflorescence (Coptis inflorescence) were studied using animal models. Serum
      total and LDL cholesterol of rats fed a diet containing 1% cholesterol and 0.5%
      cholic acid increased, as compared with those of rats fed a normal diet. The
      level of total and LDL cholesterol were reduced markedly in a dose dependent
      manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5
      g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence
      extract showed a significant (p < 0.05) blood sugar lowering activity at all
      experimented doses (0.125, 0.25 and 0.5 g/kg.day). The highest reduction of blood
      sugar was about 58% when the rats were given Coptis inflorescence extract orally
      at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis
      inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine
      and 0.66 g jatrorrhizine, which had long been identified as active compounds in
      Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis
      inflorescence would be effective in the prevention and management of coronary
      artery disease by lowering serum cholesterol and blood sugar.

PMID- 17031606
TI  - Assessing the generalization of psychopathy in a clinical sample of domestic
      violence perpetrators.
AB  - This study proposed that domestic violence perpetrators in a clinical sample
      could be categorized into distinct subgroups and that a particular subgroup of
      batterers would exhibit sufficient psychopathic characteristics to be clinically
      meaningful. Participants were interviewed in order to gather a relevant social,
      familial, educational, criminal, and substance abuse history. They were then
      administered several psychological measures including the Psychopathy Checklist:
      Screening Version (PCL:SV). Results lent support to the empirical batterer
      typology identified by Holtzworth-Munroe, A., Meehan, J. C., Herron, K., Rehman,
      U., & Stuart, G. L. (2000). However, despite the presence of a more antisocial
      subgroup, psychopathy did not consistently differentiate among batterers across
      the measured dependent variables.

PMID- 17031607
TI  - An evaluation of contaminated estuarine sites using sediment quality guidelines
      and ecological assessment methodologies.
AB  - Toxic contaminants may enter estuarine ecosystems through a variety of pathways.
      When sediment contaminant levels become sufficiently high, they may impact
      resident biota. One approach to predict sediment-associated toxicity in estuarine
      ecosystems involves the use of sediment quality guidelines (ERMs, ERLs) and site
      specific contaminant chemistry while a second approach utilizes site-specific
      ecological sampling to assess impacts at the population or community level. The
      goal of this study was to utilize an integrated approach including chemical
      contaminant analysis, sediment quality guidelines and grass shrimp population
      monitoring to evaluate the impact of contaminants from industrial sources. Three
      impacted sites and one reference site were selected for study. Grass shrimp
      populations were sampled using a push-netting approach. Sediment samples were
      collected at each site and analyzed for metals, polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs) and pesticides. Contaminant levels were
      then compared to sediment quality guidelines. In general, grass shrimp population
      densities at the sites decreased as the ERM quotients increased. Grass shrimp
      densities were significantly reduced at the impacted site that had an ERM
      exceedance for chromium and the highest Mean ERM quotient. Regression analysis
      indicated that sediment chromium concentrations were negatively correlated with
      grass shrimp density. Grass shrimp size was reduced at two sites with
      intermediate levels of contamination. These findings support the use of both
      sediment quality guidelines and site-specific population monitoring to evaluate
      the impacts of sediment-associated contaminants in estuarine systems.

PMID- 17031608
TI  - Soft tissue calcifications in the lower extremities of severely diabetic patients
      simulating venous stasis or collagen vascular disease.
AB  - The purpose of this work is to report soft tissue calcifications in severely
      diabetic patients that simulate venous stasis or scleroderma, without other
      stigmata of these diseases. Findings from lower extremity radiographs were
      reviewed on two patients with severe diabetes mellitus and abnormal soft tissue
      calcifications. Findings were correlated with clinical history, physical exam
      findings, and laboratory values. Both patients in this study demonstrate
      radiographic findings of lower extremity soft tissue calcifications similar to
      those seen in venous stasis or scleroderma. Clinical history, physical
      examination, and laboratory values support severe diabetes mellitus, with no
      evidence of these other disease entities. Patients with severe diabetes mellitus
      may exhibit soft tissue calcifications of their lower extremities that may
      simulate the changes of venous stasis or scleroderma. This association has not
      been previously described.

PMID- 17031609
TI  - The introgression of chromosome 6P specifying for increased numbers of florets
      and kernels from Agropyron cristatum into wheat.
AB  - A wheat (Triticum aestivum L.) line 4844 with superior numbers of florets and
      grains per spike was derived from the cross between Fukohokomugi wheat and
      Agropyron cristatum (L.) Gaertn. In order to determine the genetic control of
      floret and kernel number per spike in this line, chromosome addition and
      substitution lines that were derived from line 4844 were characterized by means
      of in situ hybridization, microsatellite (SSR), and gliadin analyses. Genomic in
      situ hybridization analysis with biotinylated P genomic DNA of A. cristatum as a
      probe demonstrated that the increased number of florets and grains in a spike was
      associated with the introgression of an A. cristatum chromosome. Fluorescence in
      situ hybridization, using a repetitive sequence, pAs1, derived from Aegilops
      squarrosa L., indicated the replacement of chromosome 6D of wheat in the wheat-A.
      cristatum chromosome substitution lines. This was confirmed by microsatellite
      analyses with wheat SSR markers specific for chromosome 6D, suggesting that the
      A. cristatum chromosome was homoeologous to group 6 and was therefore designated
      as 6P. This conclvsion was further confirmed by amplification using EST-SSR
      markers and gliadin analysis. The increased number of florets and kernels within
      a spike of the wheat-A. cristatum hybrids thus was controlled by gene(s) located
      on A. cristatum chromosome 6P.

PMID- 17031610
TI  - Association of variants of transcription factor 7-like 2 (TCF7L2) with
      susceptibility to type 2 diabetes in the Dutch Breda cohort.
AB  - AIM/HYPOTHESIS: A strong association between susceptibility to type 2 diabetes
      and common variants of transcription factor 7-like 2 (TCF7L2), encoding an
      enteroendocrine transcription factor involved in glucose homeostasis, has been
      reported in three different populations (Iceland, Denmark and USA) by Grant et
      al. We aimed to replicate these findings in a Dutch cohort. METHODS: We analysed
      the genotypes of two intronic single nucleotide polymorphisms (SNPs) in TCF7L2
      gene in 502 unrelated type 2 diabetes patients and in a set of healthy controls
      (n = 920). The two SNPs showed almost complete linkage disequilibrium (D' =
      0.91). RESULTS: We were able to replicate the previously reported association in
      our Breda cohort. The minor alleles of both variants were significantly over
      represented in cases (odds ratio [OR] 1.29, 95% CI 1.09-1.52, [Formula: see text]
      for rs12255372; OR 1.41, 95% CI 1.19-1.66, [Formula: see text] for rs7903146). In
      addition, TCF7L2 haplotypes were analysed for association with the disease. The
      analysis of haplotypes did not reveal any strong association beyond that expected
      from analysing individual SNPs. The TT haplotype carrying the minor alleles was
      more frequent among cases (OR 1.38, [Formula: see text]).
      CONCLUSIONS/INTERPRETATION: Our data strongly confirm that variants of the TCF7L2
      gene contribute to the risk of type 2 diabetes. The population-attributable risk
      from this factor in the Dutch type 2 diabetes population is 10%.

PMID- 17031611
TI  - Certifying diabetes-related cause-of-death: a comparison of inappropriate
      certification statements in Sweden, Taiwan and the USA.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess differences in the
      certification practices of physicians in Sweden, Taiwan and the USA with regard
      to diabetes-related cause-of-death (COD) statements. METHODS: Multiple-cause-of
      death data from Sweden (2000), Taiwan (2001) and the USA (2001) were used for
      this study. All deaths with mention of diabetes anywhere on the death certificate
      were extracted for analysis. Two types of inappropriate COD statements were: (1)
      reporting two or more diagnoses per line; and (2) entering an incorrect causal
      sequence among reported diagnoses. RESULTS: Of those deaths in which diabetes was
      reported in Part I of the death certificate, American physicians (19%) were less
      likely to report two or more diagnoses per line than physicians in Sweden (46%)
      and Taiwan (56%). On the other hand, Swedish physicians (5%) were less likely to
      report incorrect causal sequences than were their counterparts in Taiwan (21%)
      and the USA (28%). CONCLUSIONS/INTERPRETATION: These findings reveal substantial
      differences in diabetes-related COD statements among physicians in Sweden, Taiwan
      and the USA, implying that caution should be used when interpreting differences
      in mortality statistics between these countries.

PMID- 17031612
TI  - Change in the cross-sectional area of a patellar tendon graft after anterior
      cruciate ligament reconstruction.
AB  - The purpose of this study was to clarify the change in the cross-sectional area
      (CSA) of a patellar tendon graft after anterior cruciate ligament (ACL)
      reconstruction, and its relationship with postoperative knee laxity. Forty
      patients (25 men and 15 women) were included in this study. Intraoperative CSA
      measurements were performed with an instrumented areamicrometer, while a magnetic
      resonance imaging (MRI) evaluation was utilized for the assessment
      postoperatively. For intraoperative measurement, the average CSA of a 10-mm wide
      patellar tendon graft was 32.3 +/- 7.0 mm2, while the average CSA measured at
      follow-up (mean: 14.8 months) was 48.8 mm2, showing a significant mean increase
      ratio of 49.4%. This value corresponded to 115% of the native ACL. The average
      CSA measured in 30 patients at 6 months was 49.7 mm2, almost equal to the value
      at the final follow-up (49.8 mm2) in the same patient group. Among potentially
      influential factors, postoperative notch width (available space for the ACL
      graft) had significant correlation with the CSA of the graft at follow-up.
      Finally, both intra- and postoperative CSA values did not correlate with
      postoperative knee laxity, indicating that a bigger graft does not guarantee a
      better laxity.

PMID- 17031613
TI  - Functional outcome and general health status in patients after arthroscopic
      release in adhesive capsulitis.
AB  - Frozen shoulder is said to be a self-limiting entity but full recovery often
      takes more than 2 years. For that, most patients are unwilling to tolerate
      painful restriction while awaiting resolution. We prospectively investigated 30
      patients (16 women, 14 men) for the outcome of arthroscopic capsular release in
      idiopathic frozen shoulder. Results were determined by the assessment of
      subjective and objective parameters to estimate both shoulder function and
      general health status. Symptoms persisted without improvement for a minimum of 6
      months of conservative treatment. Preoperative average American shoulder and
      elbow surgeons score (ASES) was 35, visual analog scale (VAS) to measure pain was
      7, and simple shoulder test (SST) was 4. Mean scores of the physical component of
      SF-36 were considerably reduced. Mean forward elevation was 85 degrees , average
      abduction was 70 degrees , mean internal rotation was 15 degrees , and mean
      external rotation was 10 degrees . Patients were followed-up at 6 weeks, 3, 6, 12
      months and by a mean of 36 months. Range of motion for all planes improved (P <
      0.05). Median VAS reduced to 2, average ASES increased to 91, and SST enhanced to
      a mean of 10 (P < 0.05). We stated improvement of the physical components in the
      SF-36 questionnaire in particular bodily pain and the role-physical score. There
      were no significant differences between the measurements in the early
      postoperative phase compared to the mid-term follow-up (P > 0.05). Our results
      demonstrate that arthroscopic release of refractory idiopathic frozen shoulder
      combined with a gentle manipulation provides reliable expectations for
      improvement in both clinical and general health status for most patients. We
      recommend the use of a limb-specific and a general-health-status questionnaire to
      conclude the benefit of the surgical intervention and contribute the optimization
      of a therapy concept more effectively.

PMID- 17031614
TI  - In vitro measurement of patellar kinematics following reconstruction of the
      medial patellofemoral ligament.
AB  - This study compares the effects of two different techniques of medial
      patellofemoral ligament (MPFL) reconstruction, and proximal soft tissue
      realignment on patellar stabilization against lateral dislocation. Eight human
      cadaver knee specimens with no radiological pathomorpholgy on a straight lateral
      view, contributing to patellofemoral instability, were mounted in a kinematic
      knee simulator and isokinetic extension was simulated. Patellar kinematics were
      measured with an ultrasound positioning system (zebris) while a 100 N laterally
      directed force was applied to the patella. The kinematics were compared with
      intact knee conditions under MPFL deficient conditions, as well as following
      dynamic reconstruction of the MPFL using a distal transfer of the semitendinosus
      tendon, following static reconstruction by a semitendinosus autograft, and
      following proximal soft tissue realignment of the patella (Insall procedure).
      Dynamic reconstruction of the MPFL resulted in no significant alteration (P =
      0.16) of patellar kinematics. Static reconstruction of the MPFL significantly
      medialized (P < 0.01) the patellar movement without, but restored intact knee
      kinematics under the laterally directed force. In contrast, following proximal
      soft tissue realignment, the patellar movement was constantly medialized and
      internally tilted (P = 0.04). Dynamic and static reconstruction of the MPFL
      create sufficient stabilization of the patella. Following proximal soft tissue
      realignment, the patellar position was over-medialized relative to intact knee
      conditions, which could lead to an overuse of the medial retropatellar cartilage.

PMID- 17031615
TI  - Induction of alpha-L-arabinofuranosidase activity by monomeric carbohydrates in
      Bifidobacterium longum and ubiquity of encoding genes.
AB  - Bifidobacterium longum can be isolated from human faeces, some strains being
      considered probiotics. B. longum NIZO B667 produces an exo-acting alpha-L
      arabinofuranosidase, AbfB, previously purified by us, that releases L-arabinose
      from arabinan and arabinoxylan. This activity was subjected to two-seven-fold
      induction by L-arabinose, D-xylose, L-arabitol and xylitol and to repression by
      glucose. Maximum activity was obtained at 48 h incubation except for D-xylose
      that was at 24 h. High concentrations (200 mM) of L-arabitol also caused
      repression of the arabinofuranosidase. A unique band of activity showing the same
      migration pattern as the purified AbfB was found in zymograms of cell free
      extracts, indicating that the activity was likely due to this sole enzyme. The
      assessment of the influence of inducers and repressors on the activity of AbfB
      and on the expression of the abfB gene by real time PCR indicated that regulation
      was transcriptional. DNA amplifications using a pair of degenerated primers
      flanking an internal fragment within alpha-L-arabinofuranosidase genes of the
      family 51 of glycoside hydrolases evidenced that these enzymes are widespread in
      Bifidobacterium. The aminoacidic sequences of bifidobacteria included a fragment
      of four to six residues in the position 136-141 that was absent in other
      microorganisms.

PMID- 17031616
TI  - Bacteriocin-like inhibitor substances produced by Mexican strains of Bacillus
      thuringiensis.
AB  - Bacteriocins are antimicrobial peptides synthesized and secreted by bacteria and
      could potentially be used as natural food preservatives. Here, we report the
      production of bacteriocin-like inhibitor substances (Bt-BLIS) by five Mexican
      strains of Bacillus thuringiensis. Bacillus thuringiensis subsp. morrisoni (LBIT
      269), B. thuringiensis subsp. kurstaki (LBIT 287), B. thuringiensis subsp kenyae
      (LBIT 404), B. thuringiensis subsp. entomocidus (LBIT 420) and B. thuringiensis
      subsp. tolworthi (LBIT 524) produced proteinaceous Bt-BLIS with high levels of
      activity against Bacillus cereus and other gram-positive bacteria. Although none
      was active against the gram-negative bacteria, Escherichia coli, Shigella species
      and Pseudomonas aeruginosa, the five Bt-BLIS demonstrated antimicrobial activity
      against Vibrio cholerae, the etiologic agent of cholera. Biochemical and
      biophysical studies demonstrated that the five Bt-BLIS could be categorized into
      two groups, those produced by LBIT 269 and 287 (Group A) and LBIT 404, 420, 524
      (Group B), based on relative time of peptide synthesis, distinctive bacterial
      target specificity and stability in a wide range of temperatures and pH. Because
      of their stability and bactericidal activities against B. cereus and V. cholerae
      agents of emetic, diarrheal and lethal syndromes in humans, these Bt-BLIS could
      potentially be used as biodegradable preservatives in the food industry.

PMID- 17031617
TI  - Biotransformation of mercury in pH-stat cultures of eukaryotic freshwater algae.
AB  - Eukaryotic algae were studied to determine their ability to biotransform Hg(II)
      under aerated and pH controlled conditions. All algae converted Hg(II) into beta
      HgS and Hg(0) to varying degrees. When Hg(II) was administered as HgCl(2) to the
      algae, biotransformation by species of Chlorophyceae (Selenastrum minutum and
      Chlorella fusca var. fusca) was initiated with beta-HgS synthesis (K (1/2) of
      hours) and concomitant Hg degrees evolution occurred in the first hour. Hg
      degrees synthesis was impeded by the formation of beta-HgS and this inhibition
      was released in C. fusca var. fusca when cellular thiols were oxidized by the
      addition of dimethylfumarate (DMF). The diatom, Navicula pelliculosa
      (Bacillariophyceae), converted a substantially greater proportion of the applied
      Hg(II) into Hg(0), whereas the thermophilic alga, Galdieria sulphuraria
      (Cyanidiophyceae), rapidly biotransformed as much as 90% of applied Hg(II) into
      beta-HgS (K (1/2) approximately 20 min). This thermophile was also able to
      generate Hg(0) even after all exogenously applied HgCl(2) had been
      biotransformed. The results suggest that beta-HgS may be the major dietary
      mercurial for grazers of contaminated eukaryotic algae.

PMID- 17031618
TI  - Sporotalea propionica gen. nov. sp. nov., a hydrogen-oxidizing, oxygen-reducing,
      propionigenic firmicute from the intestinal tract of a soil-feeding termite.
AB  - An unusual propionigenic bacterium was isolated from the intestinal tract of the
      soil-feeding termite Thoracotermes macrothorax. Strain TmPN3 is a motile, long
      rod that stains gram-positive, but reacts gram-negative in the KOH test. It forms
      terminal endospores and ferments lactate, glucose, lactose, fructose, and
      pyruvate to propionate and acetate via the methyl-malonyl-CoA pathway. Propionate
      and acetate are formed at a ratio of 2:1, typical of most propionigenic bacteria.
      Under a H(2)/CO(2) atmosphere, the fermentation product pattern of glucose,
      fructose, and pyruvate shifts towards propionate formation at the expense of
      acetate. Cell suspensions reduce oxygen with lactate, glucose, glycerol, or
      hydrogen as electron donor. In the presence of oxygen, the product pattern of
      lactate fermentation shifts from propionate to acetate production. 16S rRNA gene
      sequence analysis showed that strain TmPN3 is a firmicute that clusters among the
      Acidaminococcaceae, a subgroup of the Clostridiales comprising obligately
      anaerobic, often endospore-forming bacteria that possess an outer membrane. Based
      on phenotypic differences and less than 92% sequence similarity to the 16S rRNA
      gene sequence of its closest relative, the termite hindgut isolate Acetonema
      longum, strain TmPN3(T) is proposed as the type species of a new genus,
      Sporotalea propionica gen. nov. sp. nov. (DSM 13327(T), ATCC BAA-626(T)).

PMID- 17031620
TI  - Recent developments in optical detection methods for microchip separations.
AB  - This paper summarizes the features and performances of optical detection systems
      currently applied in order to monitor separations on microchip devices.
      Fluorescence detection, which delivers very high sensitivity and selectivity, is
      still the most widely applied method of detection. Instruments utilizing laser
      induced fluorescence (LIF) and lamp-based fluorescence along with recent
      applications of light-emitting diodes (LED) as excitation sources are also
      covered in this paper. Since chemiluminescence detection can be achieved using
      extremely simple devices which no longer require light sources and optical
      components for focusing and collimation, interesting approaches based on this
      technique are presented, too. Although UV/vis absorbance is a detection method
      that is commonly used in standard desktop electrophoresis and liquid
      chromatography instruments, it has not yet reached the same level of popularity
      for microchip applications. Current applications of UV/vis absorbance detection
      to microchip separations and innovative approaches that increase sensitivity are
      described. This article, which contains 85 references, focuses on developments
      and applications published within the last three years, points out exciting new
      approaches, and provides future perspectives on this field.

PMID- 17031619
TI  - Phytotoxicity assessment of diclofenac and its phototransformation products.
AB  - The occurrence of pharmaceuticals in the environment is an emerging issue.
      Several studies observed that the non-steroidal anti-inflammatory drug diclofenac
      is ubiquitously present in most of the surveyed surface waters, worldwide.
      Phototransformation of diclofenac was reported from laboratory assays as well as
      in natural water systems, raising the question of possible adverse effects of the
      phototransformation products of diclofenac to aquatic organisms. In this study
      the phytotoxicity of diclofenac exposed to natural sunlight was evaluated using
      synchronized cultures of the unicellular chlorophyte Scenedesmus vacuolatus.
      Diclofenac dissolved in ultra-pure water at 50 mg L(-1) was exposed to natural
      midsummer sunlight for a maximum of 145 h. Twice a day subsamples were taken for
      chromatography and parallel phytotoxicity assessment. Inhibition of algal
      reproduction of the initial diclofenac solution was in the mg L(-1) range
      indicating no specific toxicity of diclofenac towards S. vacuolatus. Fast
      degradation of diclofenac was observed with half lives between 3.3 and 6.4 h
      during the first and the third day of exposure, respectively. Phytotoxicity
      increased after 3.5 h of exposure of diclofenac to sunlight and showed a maximum
      of sixfold enhanced toxicity after 53 h of exposure to sunlight. Several
      phototransformation products were found during the experiment. The time courses
      of the relative concentration of three transformation products significantly
      correlated with enhanced phytotoxicity during the experiment. This indicates a
      high toxicity potential of phototransformation products of diclofenac at
      concentration levels that may come close to environmental concentrations of
      residual diclofenac after degradation. We conclude that toxicity assessment of
      phototransformation products should be included in the risk assessment of
      pharmaceuticals in the environment.

PMID- 17031621
TI  - Study of normal colorectal tissue by FT-Raman spectroscopy.
AB  - FT-Raman spectroscopy was employed to study normal human colorectal tissues in
      vitro with the aim of evaluating the spectral differences of the complex colon
      mucous in order to establish a characteristic Raman spectrum. The samples were
      collected from 39 patients, providing 144 spectra for the statistical analysis.
      The results enable one to establish three well-defined spectroscopic groups of
      non-altered colorectal tissues that were consistently checked by statistical
      (clustering) and biological (histopathology) analyses: group 1 is represented by
      samples with the presence of epithelial layer, connective tissue papillae, and
      smooth muscle tissue; group 2 comprises tissues with epithelial layer and
      connective tissue papillae; group 3 presented mostly fatty and slack conjunctive
      tissue. The study reveals the existence of an intrinsic spectral variability for
      each patient that must be considered when sampling tissues fragments to build a
      spectral database. This is the first step for future studies and applications of
      Raman spectroscopy to optical biopsy and diagnosis of colorectal cancer.

PMID- 17031622
TI  - Occurrence and analysis of pharmaceuticals and their transformation products in
      drinking water treatment.

PMID- 17031623
TI  - A rapid analytical method for predicting the oxygen demand of wastewater.
AB  - In this study, an investigation was undertaken to determine whether the
      predictive accuracy of an indirect, multiwavelength spectroscopic technique for
      rapidly determining oxygen demand (OD) values is affected by the use of
      unfiltered and turbid samples, as well as by the use of absorbance values
      measured below 200 nm. The rapid OD technique was developed that uses UV-Vis
      spectroscopy and artificial neural networks (ANNs) to indirectly determine
      chemical oxygen demand (COD) levels. It was found that the most accurate results
      were obtained when a spectral range of 190-350 nm was provided as data input to
      the ANN, and when using unfiltered samples below a turbidity range of 150 NTU.
      This is because high correlations of above 0.90 were obtained with the data using
      the standard COD method. This indicates that samples can be measured directly
      without the additional need for preprocessing by filtering. Samples with
      turbidity values higher than 150 NTU were found to produce poor correlations with
      the standard COD method, which made them unsuitable for accurate, real-time, on
      line monitoring of OD levels.

PMID- 17031624
TI  - Determination of pharmaceuticals from different therapeutic classes in
      wastewaters by liquid chromatography-electrospray ionization-tandem mass
      spectrometry.
AB  - A sensitive analytical method has been developed and validated for simultaneous
      determination of pharmaceuticals from different therapeutic classes, i.e. five
      sulfonamide (SA) and trimethoprim antimicrobials and the anti-inflammatory drug
      diclofenac, in effluent wastewaters at trace levels. Effluent samples from
      treatment of wastewater were enriched by solid-phase extraction (SPE) using the
      Waters Oasis HLB cartridge. The analytes were identified and quantified by
      reversed-phase liquid chromatography-tandem mass spectrometry operated in the
      selected reaction monitoring (SRM) mode, using positive electrospray ionization.
      The pharmaceuticals were, consequently, quantified both by use of isotopically
      labelled internal standards and by standard addition methods to address the issue
      of matrix effects related to signal suppression by co-eluting compounds. Average
      recoveries from fortified samples were usually >70%, with relative standard
      deviations below 20%. Method detection limits in wastewater matrices were between
      7.0 and 10 ng L(-1). Identification points (IPs) were used for unequivocal
      identification of target analytes in real samples. Diclofenac, trimethoprim, and
      sulfamethoxazole were mainly detected, in the concentration range 10 to 400 ng L(
      1), in effluent samples collected from four different sewage-treatment plants in
      Greece.

PMID- 17031625
TI  - Stacked films immobilization of MBTH in nafion/sol-gel silicate and horseradish
      peroxidase in chitosan for the determination of phenolic compounds.
AB  - The stacked-film immobilization of 3-methyl-2-benzothiazolinone hydrazone (MBTH)
      in hybrid nafion/sol-gel silicate film and horseradish peroxidase (HRP) in
      chitosan, performed in order to allow the determination of phenolic compounds,
      was investigated via an optical method. The stacked films were deposited onto a
      microscope glass slide by a spin-coating technique. The quinone or free radical
      product formed by the enzymatic reactions of phenolic compounds interacts with
      MBTH to form azo-dye products, which can be measured spectrophotometrically at a
      wavelength of 500 nm. The color intensity of the product was found to increase in
      proportion to the phenolic concentration after 5 min of exposure. The response of
      the biosensor was linear over concentration ranges of 0.025-0.500, 0.010-0.070
      and 0.050-0.300 mM for guaiacol, resorcinol and o-cresol, respectively, and gave
      detection limits of 0.010, 0.005 and 0.012 mM. The sensor exhibited good
      sensitivity and stability for at least two months.

PMID- 17031626
TI  - Microstructure and chemical composition of giant avian eggshells.
AB  - The microstructure and composition of the layers of two giant avian eggshells
      were investigated using a combination of scanning electron microscopy, electron
      probe microanalyses, and X-ray absorption near-edge structure spectroscopy
      (XANES). The two species have some similarities and differences in their
      microstructure and composition; the composition is not homogeneous throughout the
      eggshell thickness. XANES studies show that sulfur is associated with amino acids
      in the inner organic membranes, whereas in the mineralised layers the sulfur is
      mainly associated with sulfated polysaccharides. These results are similar to
      those obtained on chicken eggshells, and confirm the active role of sulfated
      acidic polysaccharides in biomineralisation processes of carbonate skeletons.

PMID- 17031627
TI  - Observation of salt-induced beta-lactoglobulin aggregation using sedimentation
      field-flow fractionation.
AB  - Sedimentation field-flow fractionation (SdFFF) was applied in order to
      characterize particle sizes of beta-lactoglobulin aggregates induced by Ca2+ or
      Zn2+. Aggregation induced by Zn2+ was faster than that induced by Ca2+. Effects
      of Zn2+ and beta-lactoglobulin concentrations, as well as contact time, on the
      aggregation of beta-lactoglobulin were examined. All factors exhibited a combined
      effect on the size of aggregates, whereby larger aggregates were obtained at
      increased concentrations of Zn2+ and beta-lactoglobulin. At fixed concentrations
      of 2% (w/v) beta-lactoglobulin and 10 mM Zn2+, the particle size of the
      aggregates increased from 0.19 microm (at 15 min) to 0.38 microm (at 2880 min).
      Further, a hyphenated technique of SdFFF and inductively coupled plasma-optical
      emission spectrometry (ICP-OES) was used to examine whether intermolecular ionic
      bridges take part in salt-induced beta-lactoglobulin aggregation. With SdFFF-ICP
      OES, protein-cation-protein cross-linkages were observed for beta-lactoglobulin
      aggregation induced by Zn2+, but not for that induced by Ca2+.

PMID- 17031628
TI  - Fiber-optic flow-through sensor for online monitoring of glucose.
AB  - A new microdialysis-based glucose-sensing system with an integrated fiber-optic
      hybrid sensor is presented. Design and dimensions of the cell are adapted for its
      coupling with commercially available microdialysis techniques, thereby providing
      a new system for continuous glucose monitoring. The glucose level is detected via
      oxygen consumption which occurs as a consequence of enzymatic reaction between
      immobilized glucose oxidase and glucose. The use of gas-permeable Tygon tubing
      ensures complete and constant air-saturation of the measuring fluid in the cell.
      Nevertheless, a reference oxygen optode is used to detect and to compensate
      response changes caused by events like bacterial growth, temperature
      fluctuations, or failure of the peristaltic pump. In contrast to widely used
      electrochemical sensors, the response of the microdialysis-based fiber-optic
      glucose sensor is highly selective, making this sensor approach particularly
      advantageous for continuous glucose monitoring of patients in intensive care
      units. The effects of flow rate, pH, temperature, and common interferences on the
      sensor response are presented and discussed in detail. The sensor is evaluated in
      vitro using a 3-day continuous test in glucose-spiked plasma. The ability to
      measure glucose in humans is demonstrated by coupling the flow-through cell and
      commercially available microdialysis catheter CMA60. A 24-h monitoring test using
      this setup is successfully applied to a healthy volunteer.

PMID- 17031629
TI  - Kinetic speciation of nickel in mining and municipal effluents.
AB  - This study presents the results of kinetic speciation of nickel in undiluted
      mining and municipal effluents and effluents diluted with receiving freshwaters
      from the surrounding environment. The dilution ratios used for the dilution of
      the effluents were arbitrarily chosen, but were representative of the prevailing
      mining practices. The purpose of the this dilution was to mimic dilution with
      natural waters that result from dilution of the mining and municipal effluents
      with receiving freshwaters, so that this study would reveal environmental
      realities that are of concern to the managers and regulators of water resources.
      Ligand exchange kinetics using the competing ligand exchange method (CLEM) was
      studied using two independent techniques: graphite furnace atomic absorption
      spectrometry (GFAAS) with Chelex 100 resin as the competing ligand, and
      adsorptive cathodic stripping voltammetry (AdCSV) with dimethylglyoxime (DMG) as
      the competing ligand to determine the percentage of Ni metal released from Ni(II)
      DOC complexes and the rate of dissociation of Ni(II)-DOC complexes. Using a
      sample containing a mixture of 30% Copper Cliff Mine effluent, 40% Sudbury
      municipal effluent and 30% Vermillion River water, both techniques gave results
      showing that the dilution of the effluent samples increased the percentage of
      nickel released from Ni(II)-DOC complexes. This increase in the release of nickel
      from the Ni(II)-DOC complexes may be of concern to managers and regulators of
      water resources. Agreement between the results of these two techniques has
      enhanced the validity of the competing ligand exchange method used by both
      techniques.

PMID- 17031630
TI  - Scanning electron microscopy and energy dispersive analysis: applications in the
      field of cultural heritage.
AB  - Scanning electron microscopy has been extensively used for the material
      characterization of objects of artistic and archaeological importance, especially
      in combination with energy dispersive X-ray microanalysis (SEM/EDX). The
      advantages and limitations of SEM/EDX are presented in a few case studies:
      analysis of pigments in cross-sections of paint layers, quantitative analysis of
      archaeological glass from the Roman period excavated in Ephesos/Turkey, and
      investigations on glasses with medieval composition concerning their weathering
      stability and degradation phenomena.

PMID- 17031631
TI  - Metabolic imaging of atrophic muscle tissue using appropriate markers in 1H and
      31P NMR spectroscopy.
AB  - INTRODUCTION: The purpose of this feasibility study was to demonstrate non
      invasive metabolic imaging of human muscular atrophy using significant changes of
      NMR signals that are related directly or indirectly to fiber necrosis. METHODS:
      Single-voxel (1)H NMR spectroscopy and two-dimensional (31)P spectroscopic
      imaging on a 1.5-T whole-body scanner were used for in vivo mapping of areas of
      muscle damage in two cases of differently localized and pronounced atrophy.
      Spectral patterns affiliated with severe and intermediate stages of degeneration
      were compared to data of healthy control tissue to derive appropriate metabolic
      markers related to lipid infiltration or high-energy (31)P metabolism. RESULTS:
      Reliable detection of atrophic tissue was achieved by the following parameters:
      (1) liposclerotic turnover is related to a drastic reduction in the water/lipid
      (1)H signal intensity ratio (up to a factor of 74 compared to adjacent healthy
      tissue); (2) the (31)P resonance of phosphocreatine (PCr) is an adequate marker
      for differentiation of intact myocells with high-energy metabolism from regions
      dominated by terminal fiber necrosis (PCr signal vanished nearly completely or
      intensity was reduced by a factor of 3 in affected muscles). Metabolic images
      based on this signal allowed accurate non-invasive localization of atrophic
      tissue. CONCLUSION: The molecular information provided by NMR spectroscopy-
      previously only used with poor localization in atrophy studies--enables access to
      both the myocell-specific high-energy metabolism and the result of lipid
      infiltration allowing non-invasive mapping of degenerate tissue. The ability to
      investigate the results of these advanced levels of atrophy would also be useful
      for studies of more subtle degrees of denervation.

PMID- 17031632
TI  - Cavernous haemangioma of the spermatic cord in a child.
AB  - We present a unique case of an 11-year-old boy with a cavernous haemangioma of
      the spermatic cord. Sonography showed a well-defined, heterogeneous echoic mass
      with internal calcifications in the paratesticular region while radiography
      showed several phleboliths in the scrotum. Both were helpful in differentiating
      this paratesticular tumour.

PMID- 17031633
TI  - Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR
      imaging: preliminary results in osteosarcomas.
AB  - BACKGROUND: During successful chemotherapy of osteosarcomas tumour size does not
      diminish significantly because the therapy has limited impact on the mineralized
      matrix of the tumour. Treatment response is considered successful if,
      histologically, more than 90% of tumour cells show necrosis. OBJECTIVE: To
      determine if osteosarcomas change their water diffusion during preoperative
      chemotherapy in relation to the amount of tumour necrosis. MATERIALS AND METHODS:
      Eight patients (age 11-19 years) with histologically proven limb osteosarcoma
      underwent T1-weighted, fat-suppressed T2-weighted and contrast-enhanced T1
      weighted spin-echo imaging together with diffusion-weighted EPI sequences (b =
      700) at 1.5 T before and after five cycles of standard chemotherapy. Tumour
      volume and apparent diffusion coefficient (ADC) maps were calculated before and
      after chemotherapy. The degree of tumour necrosis after chemotherapy was assessed
      using the histological Salzer-Kuntschik classification (grades 1-6). RESULTS:
      During chemotherapy, the ADC values of osteosarcomas changed significantly. The
      ADC of untreated tumour was 2.1 +/- 0.4 x 10(-3) mm(2)/s (mean +/- SD) (95% CI
      1.6-2.0). The ADC of chemotherapy-treated sarcomas was 2.5 +/- 0.4 x 10(-3)
      mm(2)/s (95% CI 1.8-2.2). Necrotic areas, which were confirmed by macroscopic
      examination, showed ADC values up to 2.7 x 10(-3) mm(2)/s. Four patients with
      little viable tumour tissue within the neoplasm (Salzer-Kuntschik grades 1-2) had
      an increase in ADC of 0.4 up to 0.7 x 10(-3) mm(2)/s. Four patients with larger
      areas of viable tumour (Salzer-Kuntschik grade 4) showed a lesser increase in ADC
      of 0.0 up to 0.3 x 10(-3) mm(2)/s. The differences in ADC values in tumour tissue
      before and after chemotherapy were highly significant (P = 0.01). CONCLUSION:
      During chemotherapy of osteosarcomas, tumour ADC changes are related to the
      degree of tumour necrosis.

PMID- 17031634
TI  - Distribution of brain infarction in children with tuberculous meningitis and
      correlation with outcome score at 6 months.
AB  - BACKGROUND: Prognostic indicators for tuberculous meningitis (TBM) offer
      realistic expectations for parents of affected children. Infarctions affecting
      the basal ganglia are associated with a poor outcome. OBJECTIVE: To correlate the
      distribution of infarction in children with TBM on CT with an outcome score (OS).
      MATERIALS AND METHODS: CT brain scans in children with TBM were retrospectively
      reviewed and the distribution of infarctions recorded. The degree of correlation
      with OS at 6 months was determined. RESULTS: There was a statistically
      significant association between all sites of infarction (P = 0.0001-0.001), other
      than hemispheric (P = 0.35), and outcome score. There was also a statistically
      significant association between all types of infarction (P = 0.0001-0.02), other
      than hemispheric (P = 0.05), and overall poor outcome. The odds ratio for poor
      outcome with bilateral basal ganglia and internal capsule infarction was 12. The
      odds ratio for poor outcome with 'any infarction' was 4.91 (CI 2.24-10.74), with
      'bilateral infarctions' 8.50 (CI 2.49-28.59), with basal ganglia infarction 5.73
      (CI 2.60-12.64), and for hemispheric infarction 2.30 (CI 1.00-5.28). CONCLUSION:
      Infarction is associated with a poor outcome unless purely hemispheric. MRI
      diffusion-weighted imaging was not part of this study, but is likely to play a
      central role in detecting infarctions not demonstrated by CT.

PMID- 17031635
TI  - Pathology of the appendix in children: an institutional experience and review of
      the literature.
AB  - BACKGROUND: The appendix can be affected by a variety of congenital and acquired
      diseases, but acute appendicitis is the most common pathology found in the
      pediatric population. OBJECTIVE: This is a retrospective review of all
      appendectomies performed during a 2-year period at a major children's hospital
      with a review of the literature regarding the most common pathologic findings.
      MATERIALS AND METHODS: The pathology database was reviewed for appendectomy
      specimens, and patient medical records were evaluated to determine the age,
      gender, race and operative diagnosis. All slides were reviewed and the histologic
      findings were recorded. RESULTS: A total of 392 appendectomies were performed,
      including 68 incidental appendectomies and 324 performed for clinical suspicion
      of acute appendicitis. In 247 of the latter, acute appendicitis was confirmed
      histologically, and of the remainder 14 were interval appendectomies, 2 had
      findings suspicious for Crohn disease, 1 confirmed diverticulitis and 60 were
      histologically negative for appendicitis. CONCLUSION: Acute appendicitis is the
      most common pathologic cause of appendectomy, but various other pathologic
      entities are found in children. Examination of the appendix is warranted even
      when it appears normal on exploration.

PMID- 17031636
TI  - Biochemical characterization of a novel 2-Cys peroxiredoxin from Antrodia
      camphorata.
AB  - Peroxiredoxins (Prxs) play important roles in antioxidation and cell signaling. A
      gene encoding a novel 2-Cys Prx was identified based on sequence homology in an
      expressed sequence tag database of the Antrodia camphorata, a medicinal mushroom
      found only in Taiwan. The 2-Cys Prx cDNA (940 bp) encodes a protein of 188 amino
      acid residues with calculated molecular mass of 20,965 Da and a pI of 5.89. The
      coding region was subcloned into pAVD10, transformed into Escherichia coli, and
      expressed as a His-tagged fusion protein. The purified enzyme was characterized
      under various conditions. The Prx retained 68% activity after being heated at 60
      degrees C for 2 min. It was stable under a broad pH range from 5 to 11. The
      enzyme activity was slightly decreased in the presence of 1% sodium dodecyl
      sulfate. The enzyme was somewhat susceptible to chymotrypsin treatment but
      resistant to digestion by trypsin.

PMID- 17031637
TI  - Effect of aniline coupling on kinetic and thermodynamic properties of Fusarium
      solani glucoamylase.
AB  - Purified glucoamylase (GA) from Fusarium solani was chemically modified by cross
      linking with aniline hydrochloride in the presence of 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide (EDC) for 1 [aniline-coupled glucoamylase-1
      (ACG-1)], 7 (ACG-7), and 13 min (ACG-13). The aniline coupling of GA had a
      profound enhancing effect on temperature, pH optima, and pK (a)'s of active site
      residues. The specificity constants (K (cat)/K (m)) of native, ACG-1, ACG-7, and
      ACG-13 were 136, 244, 262, and 208 at 55 degrees C for starch, respectively. The
      enthalpy of activation (DeltaH*) and free energy of activation (DeltaG*) for
      soluble starch hydrolysis were lower for the chemically modified forms compared
      to native GA. Proteolysis of ACGs by alpha-chymotrypsin and subtilisin resulted
      in activation.

PMID- 17031638
TI  - Sustained generation of electricity by the spore-forming, Gram-positive,
      Desulfitobacterium hafniense strain DCB2.
AB  - Desulfitobacterium hafniense strain DCB2 generates electricity in microbial fuel
      cells (MFCs) when humic acids or the humate analog anthraquinone-2,6-disulfonate
      (AQDS) is added as an electron-carrying mediator. When utilizing formate as fuel,
      the Gram-positive, spore-forming bacterium generated up to 400 mW/m2 of cathode
      surface area in a single-chamber MFC with a platinum-containing air-fed cathode.
      Hydrogen, lactate, pyruvate, and ethanol supported electricity generation, but
      acetate, propionate, and butyrate did not. Scanning electron microscopy indicated
      that strain DCB2 colonized the surface of a current-generating anode but not of
      an unconnected electrode. The electricity was recovered fully within minutes
      after the exchange of the medium in the anode chamber and within a week after an
      exposure of a colonized anode to 90 degrees C for 20 min. Of the six strains of
      Desulfitobacteria tested, all of which would reduce AQDS, only D. hafniense
      strain DCB2 continued to reduce AQDS and generate electricity for more than 24 h,
      indicating that reduction of the humate analog alone is insufficient to sustain
      electrode reduction.

PMID- 17031639
TI  - Differential regulation of manganese peroxidases and characterization of two
      variable MnP encoding genes in the white-rot fungus Physisporinus rivulosus.
AB  - Manganese peroxidase (MnP) production in the white-rot basidiomycete
      Physisporinus rivulosus T241i was studied. Separate MnP isoforms were produced in
      carbon-limited liquid media supplemented with Mn(2+), veratryl alcohol, or
      sawdust. The isoforms had different pH ranges for the oxidation of Mn(2+) and 2,6
      dimethoxyphenol. Although lignin degradation by white-rot fungi is often
      triggered by nitrogen depletion, MnPs of P. rivulosus were efficiently produced
      also in the presence of high-nutrient nitrogen, especially in cultures
      supplemented with veratryl alcohol. Two MnP encoding genes, mnpA and mnpB, were
      identified, and their corresponding cDNAs were characterized. Structurally, the
      genes showed marked dissimilarity, and the expression of the two genes implicated
      quantitative variation and differential regulation in response to manganese,
      veratryl alcohol, or sawdust. The variability in regulation and properties of the
      isoforms may widen the operating range for efficient lignin degradation by P.
      rivulosus.

PMID- 17031640
TI  - Vaccination therapy in prostate cancer.
AB  - Radical prostatectomy and radiation therapy provide excellent localized prostate
      cancer (PC) control. Although the majority of prostate carcinoma is nowadays
      diagnosed at early stages with favourable risk features, in patients up to 30-40%
      it recurs within 10 years. Furthermore, the lack of effective therapies, once
      prostate carcinoma becomes refractory to androgen deprivation, mandates the
      development of alternative therapeutic options. There is a growing interest in
      harnessing the potency and specificity of anti-tumour immunity through the
      generation of fully competent dendritic cells and tumour reactive effector
      lymphocytes. Several strategies to treat or prevent the development of metastatic
      PC have been explored in clinical trials and are summarized in this review,
      considering also the feasibility and safety of these approaches. In some cases
      clinical responses were achieved showing that vaccine-primed T cells induced anti
      tumour activity in vivo. The present findings and perspectives of the immunologic
      interventions in PC patients will be discussed.

PMID- 17031641
TI  - N-acetylneuraminic acid coupled human recombinant TNFalpha exhibits enhanced anti
      tumor activity against Meth-A fibrosarcoma and reduced toxicity.
AB  - In order to study the effect of glycosylation on its biological activities and to
      develop tumor necrosis factor alpha (TNFalpha) with less deleterious effects, N
      acetylneuraminic acid (NeuAc) with a C9 spacer was chemically coupled to human
      recombinant TNFalpha. NeuAc-coupled TNFalpha (NeuAc-TNFalpha) exhibited reduced
      activities in vitro by about threefold compared to native TNFalpha. In this
      study, we examined a variety of TNFalpha activities in vivo. NeuAc-TNFalpha
      reduced activities in the up-regulation of serum levels of IL-6 and NOx, but
      comparable activity as native TNFalpha in the down-regulation of the serum level
      of glucose. However, NeuAc-TNFalpha was more potent than TNFalpha in the up
      regulation of the serum level of serum amyloid A (SAA). NeuAc-TNFalpha was less
      toxic to mice. In addition, NeuAc-TNFalpha exhibited an augmented anti-tumor
      activity against Meth-A fibrosarcoma without hemorrhagic necrosis. These results
      indicate that coupling with NeuAc enabled us to develop neoglycoTNFalpha with
      selective activities in vivo, including enhanced anti-tumor activity but reduced
      toxicity.

PMID- 17031642
TI  - Synthesis of glycosylated human tumor necrosis factor alpha coupled with N
      acetylneuraminic acid.
AB  - In order to study the effect of glycosylation on its biological activities, and
      to develop TNFalpha with less deleterious effects, recombinant human TNFalpha was
      chemically coupled with N-acetylneuraminic acid (NeuAc). NeuAc with C9 spacer was
      coupled to TNFalpha by acyl azide method. Two glycosylated TNFalphas, designated
      L NeuAc-TNFalpha and H NeuAc-TNFalpha, were purified by anion-exchange
      chromatography. NeuAc coupling to TNFalpha was confirmed by lectin blotting.
      Average number of carbohydrate molecules introduced per molecule of L NeuAc
      TNFalpha and H NeuAc-TNFalpha were estimated to be 1.0 and 1.5, respectively. We
      examined a variety of TNFalpha activities in vitro, including antiproliferative
      or cytotoxic activities to tumor cells, proliferative effect on fibroblast cells,
      stimulatory effects on IL-6 production by melanoma cells and NF-kappaB activation
      in hepatoma cells. L NeuAc-TNFalpha and H NeuAc-TNFalpha exhibited reduced
      activities about 1/3 and 1/10 as compared to native TNFalpha in all the
      activities performed in vitro.

PMID- 17031643
TI  - Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first
      line treatment of patients with metastatic non-small cell lung cancer (NSCLC):
      results of a multicentre randomized phase II trial.
AB  - BACKGROUND: Most patients (pts) with metastatic non-small cell lung cancer
      (NSCLC) receive either single agents or chemotherapy doublets. Recent studies
      have demonstrated that triple-agent therapies may improve the response rate, but
      are associated with significant toxicity, and frequently do not prolong survival.
      A sequential triple-agent schedule may combine acceptable tolerability and good
      efficacy. We therefore conducted a multicentre, prospectively randomized study
      that evaluates a sequential three-drug schedule and a platinum-free doublet
      regimen. PATIENTS AND METHODS: The pts with union international contre le cancer
      (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem,
      they received gemcitabine (900 mg/m(2), 30 min infusion) on days 1 and 8, and
      docetaxel (75 mg/m(2), 1 h infusion) on day 1, repeated every 3 weeks up to six
      cycles. In arm Cis-Gem-->Doc, gemcitabine (900 mg/m(2), days 1 and 8) and
      cisplatin (70 mg/m(2), 1 h infusion, day 1) were given for three cycles, followed
      by three cycles of docetaxel (100 mg/m(2), day 1, repeated every 3 weeks).
      RESULTS: One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts)
      and Cis-Gem-->Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment
      whereas 31.0% responded in arm Cis-Gem-->Doc (overall response, intent-to-treat,
      difference not significant). The median time to progression was 3.6 months in arm
      Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem-
      >Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem
      (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem-->Doc (95% CI 7.8,
      11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate
      leukopenia was frequently seen with both schedules. Other common adverse events
      (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections.
      No significant differences in AEs were observed between the schedules except for
      nausea/vomiting, which occurred more frequently with Cis-Gem-->Doc. CONCLUSION:
      The sequential therapy comprising cisplatin, gemcitabine, and docetaxel
      demonstrated promising tumour control whereas the platinum-free combination
      (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted
      in comparable survival to recent large trials in pts with advanced NSCLC. The
      present results do not justify further phase III investigation.

PMID- 17031644
TI  - Differential effects of the immunosuppressive agents cyclosporin A, tacrolimus
      and sirolimus on drug transport by multidrug resistance proteins.
AB  - PURPOSE: We sought to determine the effects of the immunosuppressants,
      cyclosporin A (CsA), tacrolimus and sirolimus, on drug transport by the ATP
      binding cassette proteins, P-glycoprotein (Pgp; ABCB1), multidrug resistance
      protein-1 (MRP-1; ABCC1) and breast cancer resistance protein (BCRP; ABCG2), and
      the major vault protein lung resistance protein (LRP). METHODS: Cellular content
      of mitoxantrone, a Pgp, MRP-1 and BCRP substrate, was measured by flow cytometry
      in cells overexpressing these proteins following incubation with and without CsA,
      tacrolimus or sirolimus. Interaction of BCRP with these compounds was studied by
      photolabeling and ATPase assays. Nuclear-cytoplasmic distribution of doxorubicin
      was studied by confocal microscopy in cells overexpressing LRP. RESULTS: CsA
      increased cellular drug uptake in cells overexpressing Pgp, MRP-1 or BCRP and
      nuclear drug uptake in cells overexpressing LRP at the clinically achievable
      concentration of 2.5 microM. Tacrolimus enhanced cellular drug uptake at 1
      microM, but not at 0.08 microM, its clinically achievable concentration, and did
      not enhance nuclear drug uptake. Sirolimus enhanced cellular drug uptake in cells
      overexpressing Pgp, MRP-1 and BCRP with optimal effects at 2.5 microM, but was
      effective at its clinically achievable concentration of 0.25 microM if cells were
      pre-incubated for at least 30 min before drug exposure, and also enhanced nuclear
      drug uptake at 0.25 microM. BCRP modulation by all three immunosuppressive agents
      was associated with competitive binding to the drug transport sites. CONCLUSIONS:
      CsA, tacrolimus and sirolimus modulate drug transport by Pgp, MRP-1 and BCRP and
      CsA and sirolimus modulate drug transport by LRP at concentrations that differ
      from immunosuppressive concentrations and maximum tolerated concentrations.

PMID- 17031645
TI  - The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line.
AB  - Cordycepin (3'-deoxyadenosine), a pure compound of Cordyceps sinensis, has been
      illustrated with anti-tumor effects. In the present study, the apoptotic effect
      of cordycepin on OEC-M1, a human oral squamous cancer cell line, was investigated
      by morphological observations, cell viability assay, annexin V-FITC analysis and
      flow cytometry methods. Results demonstrated that the number of rounded-up cell
      increased as treatment duration of cordycepin (100 microM) increased from 3 to 48
      h, and the plasma membrane blebbing could be observed after 12 h treatment. In
      cell viability assay, cell surviving rate significantly decreased as the dosage
      and duration of cordycepin treatment increased (P < 0.05). Moreover,
      phosphatidylserine flipping on cell membrane could be detected with 3, 6 and 12 h
      cordycepin treatment, which indicated an early apoptotic phenomenon. Furthermore,
      cell cycle studies illustrated that the percentage of G1 phase cell declined as
      the dosages of cordycepin increased (10 microM to 5 mM), while the percentages of
      G2M and subG1 phase cell increased (P < 0.05) in 12, 24 and 48 h cordycepin
      treatment. These results further confirmed the apoptotic event. In conclusion,
      cordycepin significantly induced cell apoptotsis in OEC-M1 human oral squamous
      cancer cells.

PMID- 17031646
TI  - A phase I/randomized phase II, non-comparative, multicenter, open label trial of
      CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and
      carboplatin alone as first-line treatment for advanced non-small cell lung cancer
      (NSCLC).
AB  - PURPOSE: To evaluate the toxicity profile and pharmacological properties of oral
      CP-547,632 alone and in combination with paclitaxel and carboplatin administered
      every 3 weeks, and to assess efficacy as measured by the objective response and
      progressive disease rates of oral CP-547,632 administered in combination with
      paclitaxel and carboplatin. PATIENTS AND METHODS: Patients with stage IIIB/IV or
      recurrent non-small cell lung cancer receiving first-line chemotherapy were
      treated with oral daily CP-547,632 in combination with paclitaxel 225 mg/m(2) and
      carboplatin AUC = 6 every 3 weeks. Pharmacokinetics parameters for CP-547,632 and
      paclitaxel were determined independently and during co-administration. RESULTS:
      Seventy patients were enrolled and 68 patients were treated, 37 in phase 1 and 31
      in phase 2 (14 with the combination and 17 with chemotherapy alone). Dose
      limiting toxicity of CP-547,632 250 mg by mouth daily in combination with
      paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical
      intervention. CP-547,632 did not significantly affect the pharmacologic profiles
      of paclitaxel and carboplatin. No subject had CR. In phase I, seven subjects
      (22.6%) had a confirmed partial response. In phase II, four subjects (28.6%)
      receiving CP-547,632 plus chemotherapy had a confirmed partial response. In the
      phase II chemotherapy alone group, four subjects (25%) had a confirmed partial
      response. CONCLUSION: The combination of CP-547,632 and paclitaxel and
      carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose
      limiting toxicity of CP-547,632 at 250 mg consisted of diarrhea and rash. CP
      547,632 did not increase the objective response rate to chemotherapy alone in
      patients with advanced non-small cell lung cancer.

PMID- 17031647
TI  - Phase I dose-escalation study of a novel antitumor agent, SR271425, administered
      intravenously in split doses (d1-d2-d3) in patients with refractory solid tumors.
AB  - BACKGROUND: SR271425 is a novel DNA-binding cytotoxic agent with a broad spectrum
      of antitumor activity in preclinical models,across a variety of the schedule of
      administration. In toxicological studies, it has been reported to prolong QTc
      proportionally to C (max). In order to circumvent this C (max)-related QTc
      prolongation, 5 phase I studies were initiated to investigate 1-h, 24-h, weekly,
      and split iv infusions. This phase I study assessed a split-dose regimen (a 1-h
      infusion on each of Days 1 to 3, repeated every 3 weeks) to establish the dose
      limiting toxicities (DLT), to recommended a phase II dose, and to characterize
      PK/PD. METHODS: Patient with advanced solid tumors, adequate bone marrow,
      hepatic, renal function and on specific cardiac criteria were eligible and "3 +
      3" design was used for dose escalation. That dose escalation was guided by PK
      data, toxicities observed and information from other ongoing phase I studies with
      SR271425. SR271425 plasma levels (PK samples) were measured using a validated LC
      MS/MS method. Careful monitoring of ECGs was done, and ECGs were read centrally.
      RESULTS: Three centers enrolled 19 heavily pretreated patients to six dose
      levels, from 75 to 450 mg/m(2)/day (i.e., 225-1,350 mg/m(2)/cycle): 12 males and
      7 females. Median age 56. Median ECOG, PS = 1. Main tumor types were brain,
      breast, gynecological, and urological. Patients received a median of 2 cycles
      (range: 1-6). NCI-CTC Grade 1-2 toxicities included nausea, vomiting, asthenia,
      rash, and yellow skin discoloration. No DLTs were reported, and there were no
      dose-limiting prolongations of QTc. Both C (end) and AUC increased in a dose
      related manner, with no evidence of accumulation between Day 1 and Day 3,
      consistent with the mean (+/-SD) terminal elimination half-life of 5.11 +/- 1.21
      h. Stable disease was observed in five cases. CONCLUSION: Split doses allow high
      cumulative exposure to SR271425 without significant toxicity, especially without
      QTc prolongation. MTD was not reached due to the early termination of the
      SR271425 program by the sponsor.

PMID- 17031648
TI  - Antitumor activity of trastuzumab in combination with chemotherapy in human
      gastric cancer xenograft models.
AB  - PURPOSE: To clarify the antitumor activity of trastuzumab and its potential as an
      effective treatment for gastric cancer patients. METHODS: Levels of HER2
      expression in tumor tissues of gastric cancer cell lines were examined using
      immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and mRNA
      quantification. Efficacy of trastuzumab was examined as a single agent or in
      combination with chemotherapeutic agents widely used clinically for gastric
      cancers in HER2-overexpressing human gastric cancer xenograft models. RESULTS:
      Two of nine human gastric cancer xenograft models, NCI-N87 and 4-1ST, showed
      overexpression of HER2 mRNA and protein by IHC (HercepTest) and HER2 gene
      amplification by FISH (Pathvysion). HER2 protein showed potent staining in
      peripheral membranes, similar to the staining pattern of breast cancer. FISH
      scores were also comparable to those of breast cancer models. Trastuzumab as a
      single agent inhibited the tumor growth in both of the HER2-overexpressing models
      but not in the HER2-negative models, GXF97 and MKN-45. In any combination with
      capecitabine, cisplatin, irinotecan, docetaxel, or paclitaxel, trastuzumab showed
      more potent antitumor activity than the anticancer agents alone. A three-drug
      combination of capecitabine, cisplatin, and trastuzumab showed remarkable tumor
      growth inhibition. In NCI-N87 in vitro, trastuzumab showed direct
      antiproliferative activity according to cell count or crystal violet dying, and
      showed indirect antitumor activity such as antibody-dependent cellular
      cytotoxicity. CONCLUSION: The antitumor activity of trastuzumab observed in human
      gastric cancer models warrants consideration of its use in clinical treatment
      regimens for human gastric cancer as a single agent or a combination drug with
      various chemotherapeutic agents.

PMID- 17031649
TI  - DNA vaccines for HIV: challenges and opportunities.
AB  - In December 2005, the UNAIDS and WHO reported that the global epidemic known as
      acquired immunodeficiency syndrome (AIDS) has claimed the lives of more than 25
      million adults and children over the past 26 years. These figures included an
      estimated 3.1 million AIDS-related deaths in 2005. Despite enormous efforts to
      control the spread of human immunodeficiency virus (HIV) new infection rates are
      on the rise. An estimated 40.3 million people are now living with HIV, including
      4.9 million new infections this past year. Nearly half of new HIV infections are
      in young people between the ages of 15 and 24. While drug therapies have helped
      sustain the lives of infected individuals in wealthy regions, they are relatively
      unavailable to the poorest global regions. This includes sub-Saharan Africa which
      has approximately 25.8 million infected individuals, more than triple the number
      of infections of any other region in the world. It is widely believed that the
      greatest hope for controlling this devastating pandemic is a vaccine. In this
      review, we will discuss the current state of DNA-based vaccines and how they
      compare to other vaccination methods currently under investigation. We will also
      discuss innovative ideas for enhancing DNA vaccine efficacy and the progress
      being made toward developing an effective vaccine.

PMID- 17031650
TI  - Therapeutic immunization for HIV.
AB  - Vaccines have entered into human clinical trials against infectious diseases and
      as therapies against cancer. The HIV virus establishes a latent infection at a
      very early stage and the T cell memory of the infected patient is rapidly
      destroyed. However, results of immunotherapy after DNA and protein immunization
      show that vaccine-induced immune responses might be present for a long period of
      time. Patients subjected to therapeutic immunization appear to do well, and to
      have a small immunological advantage, which, however, will have to be improved.
      The vaccine therapy should start early, while adequate reservoirs of appropriate
      T helper cells are available and still inducible. The DNA vaccines induce a
      relatively long-lived immunological memory, and gene-based immunization is
      effective in inducing cytotoxic CD8(+) T cells and CD4+ helper cells. Protein
      vaccines, on the other hand, primarily give T cell help. It thus appears that DNA
      and protein approaches to HIV immunization complement each other. A surprisingly
      broad reactivity to peptides from different subtypes of HIV was identified in
      individuals infected with several subtypes of HIV.

PMID- 17031651
TI  - Transgenic rice plants expressing trichothecene 3-O-acetyltransferase show
      resistance to the Fusarium phytotoxin deoxynivalenol.
AB  - Fusarium head blight (FHB) is a devastating disease of small grain cereal crops
      caused by the necrotrophic pathogen Fusarium graminearum and Fusarium culmorum.
      These fungi produce the trichothecene mycotoxin deoxynivalenol (DON) and its
      derivatives, which enhance the disease development during their interactions with
      host plants. For the self-protection, the trichothecene producer Fusarium species
      have Tri101 encoding trichothecene 3-O-acetyltransferase. Although transgenic
      expression of Tri101 significantly reduced inhibitory action of DON on tobacco
      plants, there are several conflicting observations regarding the phytotoxicity of
      3-acetyldeoxynivalenol (3-ADON) to cereal plants; 3-ADON was reported to be
      highly phytotoxic to wheat at low concentrations. To examine whether cereal
      plants show sufficient resistance to 3-ADON, we generated transgenic rice plants
      with stable expression and inheritance of Tri101. While root growth of wild-type
      rice plants was severely inhibited by DON in the medium, this fungal toxin was
      not phytotoxic to the transgenic lines that showed trichothecene 3-O-acetylation
      activity. This is the first report demonstrating the DON acetylase activity and
      DON-resistant phenotype of cereal plants expressing the fungal gene.

PMID- 17031653
TI  - Auditory feedback is necessary for long-term maintenance of high-frequency sound
      syllables in the song of adult male budgerigars (Melopsittacus undulatus).
AB  - Among avian species that communicate using vocalization, songbirds (oscine
      Passeriformes), hummingbirds (Trochiliformes), and parrots (Psittaciformes) are
      vocal learners. Early studies showed that songbirds require auditory feedback for
      song development in young and maintenance in adults. To determine whether
      auditory feedback is also necessary for adult song maintenance in non-passerine
      species, we deprived adult male budgerigars (Psittaciformes) of auditory input by
      surgical cochlear removal. Songs of the deafened birds changed within 6 months
      after auditory deprivation. In postoperative songs, high narrowband syllables,
      which comprised frequency-modulated narrowband elements with relatively high
      fundamental frequencies of 2-4 kHz, decreased significantly. High harmonic
      broadband syllables, with fundamental frequencies >/=2 kHz, also decreased. The
      altered proportions of syllables were subsequently retained, and maintained 12
      months after deafening. The sequence linearity score, a parameter representing
      the stereotypy of the syllable sequence, was higher than that before deafening.
      The inter-syllable silence was prolonged. Little change was observed in the songs
      of intact and sham-operated birds. The significant decrease in high-frequency
      syllables and song alteration followed by stabilization resembled the results
      with songbirds, although song stabilization took a long time in budgerigars.
      Therefore, our results suggest that psittacine budgerigars and oscine songbirds
      require auditory feedback similarly for adult song maintenance.

PMID- 17031652
TI  - State-of-the-art management of metastatic disease at initial presentation or
      recurrence.
AB  - Carcinoma of the bladder is the second most prevalent genitourinay malignancy and
      the fifth most common solid tumor in the USA. On the basis of favorable response
      rates and survival data, cisplatin-based regimens can be considered the standard
      treatment for fit patients with metastatic urothelial cancer. Since cisplatin
      containing regimens are contraindicated for patients with impaired renal
      function, gemcitabine plus either paclitaxel or docetaxel may be an effective and
      well-tolerated treatment option for these patients. Randomized trials are needed
      to determine the future role of these combinations in the management of advanced
      transitional cell carcinoma. The optimal regimens for the medically unfit
      patients and second-line chemotherapy remain undefined. Postchemotherapy surgical
      resection of residual cancer may result in a disease-free survival in highly
      selected patients who would otherwise die of the disease. Progresses in the
      understanding of the molecular biology of bladder cancer and identification of
      new targeted therapies will undoubtedly provide new opportunities but whether or
      not this approach to therapy will lead to better results must still be
      determined.

PMID- 17031655
TI  - Tau and alpha-synuclein brainstem pathology in Alzheimer disease: relation with
      extrapyramidal signs.
AB  - Extrapyramidal symptoms (EPS) in Alzheimer disease (AD) often increase with
      disease severity. Their neuropathological substrate is a matter of discussion. We
      investigated tau and alpha-synuclein (AS) pathologies in brainstem in AD patients
      with and without EPS. Among 160 elderly subjects with autopsy-proven AD (110
      female, 50 male, aged 61-102, mean 84.1 +/- 8.3 SD years), 151 (94.4%) being
      demented, 35 (21.9%) had clinically reported EPS (rigidity, bradykinesia, gait
      impairment). Neuropathological examination included standardized classification
      of AD according to current criteria, and semiquantitative assessment of neuronal
      loss in substantia nigra (SN), locus coeruleus (LC), and of tau and AS lesions in
      brainstem, and, in addition, of cerebrovascular lesions. The prevalence of EPS
      was only slightly more frequent in higher Braak stages. Tau pathology in
      brainstem significantly increased with increasing Braak stages, while AS lesions
      did not. EPS correlated best with SN cell loss (P < 0.001) and much less with AS
      pathology in several brain areas (P < 0.05), except in medulla oblongata (P <
      0.001). Although both pathologies in substantia nigra correlated with neuron loss
      (P < 0.001), nigral tau lesions, present in 88.5% of EPS positive cases (without
      AS lesions in 55.6%), did not correlate with EPS. Additional cerebrovascular
      changes apparently did not influence the development of EPS symptoms in fully
      developed AD. With other recent data, these results suggest that neuronal loss in
      SN, partly related to tau lesions, is a major pathological substrate of EPS in
      AD, but some cases with and without EPS may show no or only minimal nigral
      changes. However, often associated with nigral tau lesions and higher Braak
      stages, EPS in elderly patients may be a surrogate marker for severe neuritic AD
      pathology.

PMID- 17031654
TI  - A randomized controlled trial comparing simultaneous intra-operative vs
      sequential prophylactic ureteric catheter insertion in re-operative and
      complicated colorectal surgery.
AB  - OBJECTIVES: Prophylactic insertion of ureteric stents aids intra-operative
      identification of ureters and may allow easier visualization of any direct
      ureteric injury. Traditionally, ureteric catheters are inserted sequentially,
      before starting the abdominal part of the operation. This study determines the
      safety and efficacy of simultaneous intra-operative ureteric catheter insertion
      during complicated and re-operative colorectal surgery. MATERIALS AND METHODS:
      After institutional review board (IRB) approval, 24 patients were randomized into
      two groups, sequential (SEQ) and simultaneous (SIM) depending upon the timing of
      stent placement relative to abdominal incision. Time taken from induction to
      abdominal incision (AIT), induction to peritoneal entry (PET), catheter insertion
      time (CIT), and urinary tract infection rates were recorded. Degree of difficulty
      for stent insertion was graded on a scale of 1-10. RESULT: Demographics were
      similar between groups. Mean AIT (22 +/- 4 vs 41 +/- 7; p = 0.0001) and mean PET
      (26 +/- 4.2 vs 44 +/- 7.6; p = 0.0001) were shorter in the SIM group. There was
      no significant difference in mean CIT in SIM and SEQ groups (17.9 +/- 4.9 vs 17.6
      +/- 5.9 min, p = 0.8). The stents were unsuccessful bilaterally in one patient in
      the SEQ group and unilaterally in two other patients, one in each group. The
      median difficulty score for catheter insertion was 3 (1-10) and 2 (1-10), (p =
      0.12), respectively, in SIM and SEQ groups. There were no ureteric injuries in
      either group. One patient in SIM developed a urinary tract infection. CONCLUSION:
      Simultaneous ureteric catheter insertion during abdominal procedures reduces
      operating times without a significant increase in morbidity. Furthermore, this
      permits a policy of selective stent insertion as required by the intra-abdominal
      findings after laparotomy.

PMID- 17031656
TI  - Genetically distinct astrocytic and oligodendroglial components in
      oligoastrocytomas.
AB  - Oligoastrocytomas are glial tumours consisting of a mixture of neoplastic
      astrocytic and oligodendroglial cells. Genetic alterations of oligoastrocytomas
      include loss of heterozygosity of chromosomes 1p and/or 19q (LOH 1p/19q),
      typically occurring in oligodendrogliomas, and mutations of TP53, frequently
      occurring in astrocytomas. To investigate whether these neoplastic cell types in
      oligoastrocytomas have different genetic profiles, we examined the two different
      components of oligoastrocytomas in comparison with the histological diagnosis of
      the specific tumour area for LOH 1p/19q and TP53 mutations by using
      microdissection technique. We found a variety of lost markers for 1p and 19q, and
      the presence of two different TP53 mutations in the tumour samples. In the
      majority of cases (9/11), the oligodendroglial and astrocytic components of an
      individual oligoastrocytoma displayed the same genotype. We present two cases of
      biphasic oligoastrocytomas with aberrant findings, suggesting the coexistence of
      genetically and morphologically distinct tumour cell clones in these tumours. In
      one case, the oligodendroglial part of the tumour showed LOH19q, whereas the
      astrocytic part showed TP53 mutation (codon 273). In another case, we found LOH
      1p/19q in the oligodendroglial component, but two retained areas on chromosome 1p
      in the astrocytic component of the tumour. No evidence was found for the
      coexistence of tumour cells with the two genotypical changes within the same
      morphological region of one individual tumour. The two cases of biphasic
      oligoastrocytomas in our sample that display a different genotype in the
      astrocytic and oligodendroglial part of the tumour show that different components
      of an oligoastrocytoma may be derived from different cell clones during
      neoplastic transformation.

PMID- 17031657
TI  - Recombinant human lactoferrin has a potential to suppresses uterine cervical
      ripening in preterm delivery in animal model.
AB  - OBJECTIVE: To investigate the effect of recombinant human lactoferrin (rhLF) on
      cervical ripening using a rabbit model in which preterm labor was induced by
      bacterial endotoxin lipopolysaccharide (LPS). STUDY DESIGN: Timed pregnant
      rabbits (New Zealand White, 3-4 kg, day 14) were randomly assigned to the
      following treatment groups: Group A, LPS + rhLF (n = 4); Group B, LPS (n = 4);
      and Group C, control (n = 4). Recombinant human lactoferrin (10 microg) was
      administrated to pregnant rabbits in Group A and not in Group B.
      Lipopolysaccharide (100 microg) was given to the rabbits in both groups for 3
      days (days14-16). Drugs were administered as a vaginal suppository. On day 18,
      the rabbits were anesthetized with intramuscular ketamine hydrochloride (20
      mg/kg) and diazepam (4 mg/kg). Both cervices of the rabbit uterus, which is
      bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution
      for a histological study with standard hematoxylin-eosin staining. The other was
      used for an extension test to assess the grade of ripening. Extension was
      measured after a 5-mm length of cervical tissue was loaded with 5.8 g. RESULTS:
      The histological study showed remarkably loose and edematous connective tissue in
      Group B cervices. Cervical tissues in Group A was not different from those in
      Group C. Extension lengths were 2.2 +/- 0.2 mm in Group A, 7.0 +/- 2.7 mm in
      Group B, and 1.7 +/- 0.3 mm in Group C. CONCLUSION: These results suggest that
      rhLF inhibits cervical maturation induced by LPS in a rabbit model and may have a
      potential to prevent preterm delivery caused by cervical infection and ripening.

PMID- 17031658
TI  - Bilateral micropapillary serous carcinoma of the ovary: a case report.
AB  - BACKGROUND: Micropapillary serous carcinoma (MPSC), a recently described entity
      in the group of serous borderline tumor, needs to be recognized and separated
      from serous borderline tumor of usual type (SBT) as MPSC has a worse prognosis.
      CASE REPORT: We report the case of a 21-year-old female with gradually increasing
      lump abdomen for 6 months. Ultrasonography showed bilateral ovarian enlargement
      with cysts. Laparotomy revealed both ovaries to be enlarged and right ovary
      showed capsular breach. With a per-operative diagnosis of bilateral malignant
      ovarian tumor, total abdominal hysterectomy with bilateral salpingo-oophorectomy
      was performed. Multiple sections from both ovaries showed non-invasive
      micropapillary serous carcinoma with right ovary showing surface growth but no
      definite capsular breach. The final histological diagnosis was bilateral
      micropapillary serous carcinoma. The patient has been asymptomatic in 10-month
      follow-up. CONCLUSION: MPSC, classified as serous borderline tumor, needs to be
      differentiated from APST as well as conventional serous carcinoma. It is
      diagnosed according to strict criteria laid down. Multiple sections should be
      studied to exclude invasion. Adequate peritoneal sampling should be performed to
      look for implants, which is of prognostic significance.

PMID- 17031659
TI  - Laryngo-tracheal profile: a new method for assessing laryngo-tracheal stenoses.
AB  - We present the clinical application of a new method for objective assessment of
      both grade and length of laryngo-tracheal stenoses (LTS) on a CT-based
      skeletonization algorithm, called laryngo-tracheal profile (LTP). Extraction of
      the laryngo-tracheal tract (LTT)-medial axis was performed after S-CT scanning.
      Orthogonal to the medial axis, the LTT cross-profile was computed, and the length
      and degree of LTS were presented as line charts. Clinical application of this
      newly developed method is demonstrated on three patients who had to undergo
      preoperative assessment before surgical treatment of tracheal stenoses. LTP
      provides an objective method of assessment of both the length and degree of
      tracheal stenoses in precise correlation to defined anatomical landmarks. This
      method provides important additive information for preoperative evaluation as
      well as for monitoring of therapeutical success. Current methods used so far are
      able to evaluate the severity of LTS, but do not provide exact quantitative
      assessment of complex LTS. Especially in CT-scans of strong curved passages,
      where an overestimation of the cross-sectional area results by an oblique cut of
      the tubular structure, LTP may overcome this problem by a simple post processing
      skeletonization algorithm.

PMID- 17031660
TI  - Fast alterations of vascular endothelial growth factor (VEGF) expression and that
      of its receptors (Flt-1, Flk-1 and Neuropilin) in the cochlea of guinea pigs
      after moderate noise exposure.
AB  - Vascular endothelial growth factor (VEGF) is a vascular permeability regulating,
      proangiogenic factor with neuroprotective properties. Its expression in the inner
      ear has been demonstrated, but little is known concerning its subcellular
      distribution or potential involvement in sound perception and adaptation to
      noise. Therefore, we determined the expression patterns and levels of VEGF and
      the three VEGF-receptors FLK, FLT and Neuropilin in the cochlea of guinea pigs,
      and examined the alterations occurring after noise exposure. After 70 dB
      exposure, VEGF expression was found to be reduced in all cell types of the organ
      of Corti, in the stria vascularis and in spiral ganglion cells. Additional down
      regulation was observed in the spiral ligament and in interdental cells after 90
      dB. In contrast, VEGF showed an in tendency increased level after both
      intensities in nerve fibers of the osseous spiral lamina. Expression of FLT was
      affected similarly, showing down-regulation after 70 and 90 dB on spiral ganglion
      cells, the nerve fibers of the osseous spiral lamina and on Deiters cells.
      Additionally, down-regulation was observed in the remaining cell types of the
      organ of Corti, the stria vascularis, the spiral ligament and the interdental
      cells. The Neuropilin levels remained unchanged by our experiments; apart from
      the blood vessel endothelium, there was no detectable expression in any of the
      cell types investigated. The FLK expression pattern was likewise unaffected by
      exposure to 70 or 90 dB, with the notable exception of an increased level
      occurring in Schwann cells after 90 dB. We postulate that modulation of VEGF and
      its receptors may be part of a neuroprotective mechanism in response to noise.

PMID- 17031661
TI  - Cytogenetic effects of low-dose radiation with different LET in human peripheral
      blood lymphocytes.
AB  - Chromosome damage and the spectrum of aberrations induced by low doses of gamma
      irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm)
      in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were
      exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations
      at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect
      dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells
      showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which
      was mainly due to chromatid-type aberration. According to the classical theory of
      aberration formation, chromatid-type aberrations should not be induced by
      irradiation of unstimulated lymphocytes. With increasing dose, the frequency of
      aberrations decreased significantly, and in some cases it even reached the
      control level. At above 50 cGy the dose-effect curves became linear. In this dose
      range, the frequency of chromatid aberrations remained at a low constant level,
      while the chromosome-type aberrations increased linearly with dose. The high
      yield of chromatid-type aberrations observed in our experiments at low doses
      confirms the idea that the molecular mechanisms which underlie the HRS phenotype
      may differ from the classical mechanisms of radiation-induced aberration
      formation. The data presented, as well as recent literature data on bystander
      effects and genetic instability expressed as chromatid-type aberrations on a
      chromosomal level, are discussed with respect to possible common mechanisms
      underlying all low-dose phenomena.

PMID- 17031662
TI  - The use of a syncytium model of the crystalline lens of the eye as a new tool to
      study the light flashes phenomenon seen by astronauts.
AB  - A syncytium model to study some electrical properties of the eye is proposed to
      study the phenomenon of anomalous light flashes (LF) perceived by astronauts in
      orbit. The crystalline lens is modelled as an ellipsoidal syncytium with a
      variable relative dielectric constant. The corresponding mathematical model is a
      boundary value problem for a system of two coupled elliptic partial differential
      equations in the two unknown syncytial electrical potentials. A numerical method
      to compute an approximate solution of this mathematical model is used, and some
      numerical results are shown. The model can be regarded as a new tool to study the
      LF phenomenon. In particular, the energy lost in the syncytium by a transversing
      cosmic charged particle is calculated and the results obtained with the syncytium
      model are compared with those obtained using the previously available Geant 3.21
      simulation program. In addition, the interaction of antimatter-syncytium is
      studied, and the Creme96 computer program is used to evaluate the cosmic ray
      fluxes encountered by the International Space Station in its standard mission.

PMID- 17031663
TI  - The role of SUMO in chromosome segregation.
AB  - Chromosome segregation is an essential feature of the eukaryotic cell cycle.
      Efficient chromosome segregation requires the co-ordination of several cellular
      processes; some of which involve gross rearrangements of the overall structure of
      the genetic material. Recent advances in the analysis of the role of SUMO (small
      ubiquitin-like modifier) and in the identification of SUMO-modified targets
      indicate that sumoylation is likely to have several key roles in regulating
      chromosome segregation This mini-review summarises the recently published data
      concerning the role of SUMO in the processes required for efficient chromosome
      segregation.

PMID- 17031664
TI  - Kinematic invariants during cyclical arm movements.
AB  - It has been observed that the motion of the arm end-point (the hand, fingertip or
      the tip of a pen) is characterized by a number of regularities (kinematic
      invariants). Trajectory is usually straight, and the velocity profile has a bell
      shape during point-to-point movements. During drawing movements, a two-thirds
      power law predicts the dependence of the end-point velocity on the trajectory
      curvature. Although various principles of movement organization have been
      discussed as possible origins of these kinematic invariants, the nature of these
      movement trajectory characteristics remains an open question. A kinematic model
      of cyclical arm movements derived in the present study analytically demonstrates
      that all three kinematic invariants can be predicted from a two-joint
      approximation of the kinematic structure of the arm and from sinusoidal joint
      motions. With this approach, explicit expressions for two kinematic invariants,
      the two-thirds power law during drawing movements and the velocity profile during
      point-to-point movements are obtained as functions of arm segment lengths and
      joint motion parameters. Additionally, less recognized kinematic invariants are
      also derived from the model. The obtained analytical expressions are further
      validated with experimental data. The high accuracy of the predictions confirms
      practical utility of the model, showing that the model is relevant to human
      performance over a wide range of movements. The results create a basis for the
      consolidation of various existing interpretations of kinematic invariants. In
      particular, optimal control is discussed as a plausible source of invariant
      characteristics of joint motions and movement trajectories.

PMID- 17031665
TI  - Patch pipettes are more useful than initially thought: simultaneous pre- and
      postsynaptic recording from mammalian CNS synapses in vitro and in vivo.

PMID- 17031666
TI  - Evidence that TRPC4 supports the calcium selective I(CRAC)-like current in human
      gingival keratinocytes.
AB  - We previously demonstrated that high external [Ca(2+)] activated two Ca(2+)
      currents in human gingival keratinocytes (HGKs): an initial small I(CRAC)-like
      current and a second large nonspecific cation current (Fatherazi S, Belton CM,
      Cai S, Zarif S, Goodwin PC, Lamont RJ, Izutsu KT; Pflugers Arch 448:93-104,
      2004). It was recently shown that TRPC1, a member of the transient receptor
      potential protein family, is a component of the store-operated calcium entry
      mechanism in keratinocytes. To further elucidate the molecular identity of these
      channels, we investigated the expression of TRPC4 in gingival tissue and in
      cultured keratinocytes, and the effect of knockdown of TRPC4 expression on the
      Ca(2+) currents and influx. Immunohistochemistry showed TRPC4 was present in
      gingival epithelium as well as in HGKs cultured in different [Ca(2+)]s. Results
      from tissue and cultured HGKs demonstrated TRPC4 expression decreased with
      differentiation. Knockdown of TRPC4 in proliferating HGKs with antisense
      oligonucleotides significantly reduced the intracellular [Ca(2+)] increase
      obtained upon exposure to high external [Ca(2+)]. Antisense knockdown of TRPC4
      expression was confirmed by reverse transcriptase polymerase chain reaction,
      Western blot, and immunofluorescence microscopy of transfected HGKs.
      Immunofluorescence microscopy and patch clamp measurements in Lucifer-yellow
      tagged, antisense-treated HGKs showed attenuation of TRPC4 expression levels as
      well as attenuation of the I(CRAC)-like current in the same cell, whereas the
      large nonspecific cation current was unchanged but significantly delayed. Cells
      transfected with a scrambled TRPC4 oligonucleotide showed no change in either the
      I(CRAC)-like or nonspecific currents. The results indicate that TRPC4 is an
      important component of the I(CRAC)-like channel in HGKs.

PMID- 17031668
TI  - High extracellular K(+) evokes changes in voltage-dependent K(+) and Na (+)
      currents and volume regulation in astrocytes.
AB  - [K(+)](e) increase accompanies many pathological states in the CNS and evokes
      changes in astrocyte morphology and glial fibrillary acidic protein expression,
      leading to astrogliosis. Changes in the electrophysiological properties and
      volume regulation of astrocytes during the early stages of astrocytic activation
      were studied using the patch-clamp technique in spinal cords from 10-day-old rats
      after incubation in 50 mM K(+). In complex astrocytes, incubation in high K(+)
      caused depolarization, an input resistance increase, a decrease in membrane
      capacitance, and an increase in the current densities (CDs) of voltage-dependent
      K(+) and Na(+) currents. In passive astrocytes, the reversal potential shifted to
      more positive values and CDs decreased. No changes were observed in astrocyte
      precursors. Under hypotonic stress, astrocytes in spinal cords pre-exposed to
      high K(+) revealed a decreased K(+) accumulation around the cell membrane after a
      depolarizing prepulse, suggesting altered volume regulation. 3D confocal
      morphometry and the direct visualization of astrocytes in enhanced green
      fluorescent protein/glial fibrillary acidic protein mice showed a smaller degree
      of cell swelling in spinal cords pre-exposed to high K(+) compared to controls.
      We conclude that exposure to high K(+), an early event leading to astrogliosis,
      caused not only morphological changes in astrocytes but also changes in their
      membrane properties and cell volume regulation.

PMID- 17031669
TI  - Embryonic expression of HeFoxA1 and HeFoxA2 in an indirectly developing
      polychaete.
AB  - Two forkhead family transcription factors, HeFoxA1 and HeFoxA2, were isolated
      from the serpulid annelid Hydroides elegans and their transcript distribution
      were characterized during embryogenesis. HeFoxA1 is first detected in second
      quartet blastomeres soon after their formation, and later in all vegetal half
      blastomeres, which comprise ectoderm, endoderm, and mesoderm precursors. HeFoxA1
      expression declines first in subtrochal ectoderm and presumptive midgut
      precursors, as well as apparently in D quadrant blastomeres in advance of any
      known signaling events. Later, during gastrulation, HeFoxA1 declines in hindgut
      precursors, and by the end of gastrulation the expression remains active only in
      foregut precursors. HeFoxA1 is apparently expressed in ectomesoderm cells
      involved in forming the larva-specific protonephridium (the so-called head
      kidney). The other ortholog, HeFoxA2, is expressed in a subset of the cells in
      which HeFoxA1 is expressed during early stages, but later it is largely
      restricted to the endoderm-ectoderm boundary of the proctodaeum. In addition,
      HeFoxA2 has a unique expression in two hindgut cells and abutting ectoderm cells
      located by the imminent anal opening. The combined expression of HeFoxA1 and
      HeFoxA2 correlates with mesoderm and endoderm expression of their orthologs in
      other bilaterians.

PMID- 17031667
TI  - Regulation of TRP channels by PIP(2).
AB  - Transient receptor potential (TRP) channels are regulated by a wide variety of
      physical and chemical factors. Recently, several members of the TRP channel
      family were reported to be regulated by phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P(2), PIP(2)). This review will summarize the current knowledge on
      PIP(2) regulation of TRP channels and discuss the possibility that PIP(2) is a
      common regulator of mammalian TRP channels.

PMID- 17031670
TI  - Human xenograft osteosarcoma models with spontaneous metastasis in mice: clinical
      relevance and applicability for drug testing.
AB  - Osteosarcoma cells derived from patients have been isolated and subsequently
      cultured for the past 35 years. To date though, there have been no major
      breakthroughs in the development of a model for osteosarcoma that uses orthotopic
      implantation of human osteosarcoma cells and that closely emulates the clinical
      progression of this debilitating and fatal disease. Such a model is long overdue
      given the devastating demographics (second highest cause of cancer-related death
      in the paediatric age group) of the ailment and the lack of solid options for
      control, if not cure, for the disease, as it also is the most common primary
      tumour of bone. Only then can more robust R & D be undertaken in the search for
      efficacious anti-osteosarcoma agents. This review tackles this conundrum and
      lists the variety of models (that use human osteosarcoma cells) available and the
      types of studies performed with these.

PMID- 17031671
TI  - Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in
      rats.
AB  - The purpose of this study is to investigate if the EGFR-Stat3 signal pathway
      contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in
      rats by 3'Me-DAB as a model. EGFR, TGFalpha, Stat3, p-Stat3 in different stages
      of carcinogenesis were detected by immunohistochemistry and Western blot. In situ
      hybridization was applied to investigate the expression of Stat3 mRNA. The
      expressions of signal molecules were assessed by KS400 Image Analysis system. The
      data were statistically evaluated. EGFR, TGFalpha, Stat3 were highly expressed in
      the stages of liver necrosis and repairment. All hepatocellular carcinoma cases
      revealed elevated expression of EGFR, TGFalpha. Elevation of Stat3 mRNA and
      protein levels were identified, increase of activation of Stat3 was also
      observed. In HCC, there was positive correlation between p-Stat3 level and the
      expression of TGFalpha and PCNA. Increased expression of Bcl-2 (P < 0.05)
      coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal
      pathway was related to the development of hepatoma in rats. TGFalpha-EGFR
      autocrine ring formation may lead to the activation of Stat3 and in turn, promote
      proliferation and regulate the transcription of genes regulating cell apoptosis
      and cell cycle.

PMID- 17031672
TI  - Assessment of formal and low structured kinetic modeling of polyhydroxyalkanoate
      synthesis from complex substrates.
AB  - A formal kinetic mathematical model for poly-(3-hydroxybutyrate-co-3
      hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolyester
      synthesis from glucose and galactose derived from whey permeate supplemented with
      gamma-butyrolactone by the archaeon Haloferax mediterranei was created. Further,
      a low structured mathematical model for poly-3-hydroxybutyrate synthesis from
      whey permeate by Pseudomonas hydrogenovora was developed. In both cases,
      biosyntheses for obtaining the experimental data used for compiling the models
      were performed via fed-batch cultivations. The model developed for H.
      mediterranei consists of 10 differential and 11 algebraic equations, including 27
      kinetic constants. The model compiled for P. hydrogenovora encompasses 10
      differential and 3 algebraic equations, including 36 kinetic constants. Both
      models were solved by Runge-Kuta variable step numerical integration with Monte
      Carlo parameter optimization procedure. Difficulties arising from the modeling of
      redirection of metabolic fluxes from biomass growth toward polyhydroxyalkanoate
      synthesis and byproducts are discussed.

PMID- 17031673
TI  - Proximal direct composite restorations and chairside CAD/CAM inlays: marginal
      adaptation of a two-step self-etch adhesive with and without selective enamel
      conditioning.
AB  - The aim of this study was to evaluate the marginal adaptation of CEREC ceramic
      inlays, CEREC composite inlays and direct composite restorations in unbeveled
      proximal slot cavities under artificial aging conditions. Two groups of each
      restoration type were prepared (n = 6), one group with a self-etch adhesive, the
      other group with H(3)PO(4) enamel etching before the self-etch adhesive
      application. Replicas were generated before and after long-term thermo-mechanical
      loading under dentinal fluid simulation and margins were evaluated at x200
      magnification in the scanning electron miscroscope (SEM). Statistically,
      significant differences were found before and after loading with respect to the
      percentages of "continuous margins", the direct composite filling with H(3)PO(4)
      enamel etching giving the lowest percentages of "continuous margins" after
      loading (p < 0.05). The highest percentage of "continuous margin" was attained by
      composite inlays without H(3)PO(4) enamel etching. However, these results were
      not significantly different from ceramic inlays after stressing. Polymerization
      shrinkage is still one critical property of composite restorative materials. The
      marginal adaptation of indirect adhesive proximal slot restorations without
      enamel bevels both fabricated out of composite and ceramic is better than that of
      directly placed composite restorations.

PMID- 17031674
TI  - Micronucleus--an upcoming marker of genotoxic damage.
AB  - This study was conceived for the early detection of oral precancer and cancer
      lesions using a noninvasive reliable technique. Micronucleus assay was performed
      on oral exfoliated cells of chosen subjects having leukoplakia and squamous cell
      carcinoma (SCC) using fluorescent (Acridine Orange) and conventional (Feulgen)
      stainings. The results were analyzed using Mann-Whitney U test, Kruskal-Wallis
      test, Spearman's Correlation and SPSS statistical package. The frequency of mean
      percentage occurrence of micronucleated cells increased significantly in
      comparison to controls with leukoplakia and squamous cell carcinoma. Subjects
      with synergism of abnormal oral habits also showed increased micronucleated
      cells. Fluorescent staining was found to be more sensitive than the conventional
      one for micronucleus detection. The results clearly demonstrate that micronucleus
      assay in oral exfoliated cells can be used as a simple reliable marker to assess
      the genotoxicity and for the early diagnosis of premalignant and malignant
      lesions. Micronucleus assay is, thus, an easy tool for early detection of cancer.

PMID- 17031675
TI  - [Ulceration of the hard palate in a 50-year-old patient].

PMID- 17031676
TI  - [Special ginkgo extract in cases of vertigo: a systematic review of randomised,
      double-blind, placebo controlled clinical examinations].
AB  - BACKGROUND: The concept for the medical treatment of vertigo has changed over the
      last 30 years due to recognition of the dependence of the vertiginous sensation
      on vestibular compensation and the dependence of vestibular compensation on the
      state of vigilance. METHODS: In this systematic review, experimental studies of
      the influence of the special ginkgo extract EGb 761 on vestibular compensation in
      animals and randomized, double-blind clinical studies of EGb 761 in vestibular
      and non-vestibular vertigo are described and critically evaluated. RESULTS: The
      beneficial effect of EGb 761 on vestibular compensation has been demonstrated in
      preclinical and clinical studies. CONCLUSION: Evidence of the efficacy of EGb 761
      for the treatment of vertiginous syndromes is presented in the available studies.

PMID- 17031677
TI  - [Differential diagnosis of chronic synovitis].
AB  - This review presents an algorithm for the standardised histopathological
      diagnostics of synovial biopsies and synovectomy specimens. In general, changes
      of the synovium can be inflammatory or non-inflammatory. To the latter group
      belong certain benign tumors such as the diffuse variant of the tenosynovial
      giant cell tumor, lipoma or synovial chondromatosis, additionally the rare group
      of storage diseases should be kept in mind. Inflammatory diseases can be
      discriminated into crystal-induced arthropathies such as gout and pseudogout,
      into granulomatous diseases such as tuberculosis, sarcoidosis and foreign-body
      inoculation, and into the large group of non-granulomatous synovitis. This group
      is by far the most common, and it often causes difficulties in assigning the
      histopathological findings to a concrete diagnosis. Therefore, the synovitis
      score should be applied as a diagnostic device in these cases, leading to the
      diagnosis of a low-grade synovitis (which is associated with degenerative
      arthropathies) or of a high-grade synovitis (associated with rheumatic diseases),
      the sensitivity and specificity being 60.5% and 95.5%, respectively.

PMID- 17031678
TI  - A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease.
AB  - Pelizaeus-Merzbacher disease (PMD) and Pelizaeus-Merzbacher-like disease (PMLD)
      are hypomyelinating disorders of the central nervous system with a very similar
      phenotype. PMD is an X-linked disorder caused by mutations in PLP1. PMLD is an
      autosomal recessive condition caused by mutations in GJA12. We report a 5-year
      old girl with a complex neurological syndrome and severe hypomyelination on brain
      magnetic resonance imaging. She harbored a homozygous 34-bp deletion in the
      coding region of GJA12. There are no distinctive features for the differential
      diagnosis of PMD/PMLD. GJA12 should be analyzed in all patients without PLP1
      mutations but should also be considered the initial genetic test in women and in
      patients with consanguineous parents.

PMID- 17031679
TI  - De novo double mutation in PAX6 and mtDNA tRNA(Lys) associated with atypical
      aniridia and mitochondrial disease.
AB  - We report on the clinical, molecular and biochemical findings of a patient with
      the rare event (<4.02 x 10(-9) per generation) of coinciding de novo mutations in
      the nuclear PAX6 (c.1252-1267del16) and the mitochondrial mt.RNA (Lys) (8347A-
      >G) genes. The boy suffers from exercise intolerance, ptosis, nystagmus, macular
      hypoplasia and anterior segment abnormalities evocative of Axenfeld-Rieger
      anomaly. The PAX6 mutation is predicted to cause haploinsufficiency. The novel
      mt.RNA (Lys) mutation is located close to the classic myoclonic epilepsy with
      ragged-red-fibers mutation, but the patient exhibits neither myoclonic epilepsy
      nor ragged-red-fibers. The degree of mutant mtDNA heteroplasmy, as determined by
      a very accurate pyrosequencing assay, varies between 31% (muscle) and 38%
      (fibroblasts). We discuss a potential effect of the PAX6 mutation on the mtDNA
      mutation rate.

PMID- 17031680
TI  - Regulation of metal transporters by dietary iron, and the relationship between
      body iron levels and cadmium uptake.
AB  - Iron (Fe) plays essential roles in biological processes, whereas cadmium (Cd) is
      a toxic and non-essential metal. Two metal transporters, divalent metal
      transporter 1 (DMT1) and metal transporter protein 1 (MTP1), are responsible for
      Fe transport in mammals. Here, we studied the effect of dietary Fe on the
      expression of these metal transporters in peripheral tissues, and the uptake by
      these tissues of Cd. Mice were fed an Fe-sufficient (FeS: 120 mg Fe/kg) or Fe
      deficient (FeD: 2-6 mg Fe/kg) diet for 4 weeks. The total Fe levels in the body
      were evaluated by measuring tissue Fe concentrations. Tissue Cd concentrations
      were determined 24 h after the mice received a single oral dose of Cd. Animals
      fed a FeD diet showed depletion of body Fe levels and accumulated 2.8-fold higher
      levels of Cd than the FeS group. Quantitative real time RT-PCR revealed that
      whereas DMT1 and MTP1 were both ubiquitously expressed in all FeS peripheral
      tissues studied, DMT1 was highly expressed in brain, kidney, and testis, whereas
      MTP1 was highly expressed in liver and spleen. Depletion of the body Fe stores
      dramatically upregulated DMT1 and MTP1 mRNA expression in the duodenum as well as
      moderately upregulating their expression in several other peripheral tissues. The
      iron response element positive isoform of DMT1 was the most prominently
      upregulated isoform in the duodenum. Thus, DMT1 and MTP1 may play an important
      role in not only maintaining Fe levels but also facilitating the accumulation of
      Cd in the body of mammals.

PMID- 17031681
TI  - Human standing and walking: comparison of the effects of stimulation of the
      vestibular system.
AB  - The adoption of bipedalism by hominids including man has complicated the tasks of
      balance control and the minimisation of body sway. We have investigated the role
      of the vestibular organs in controlling sway in the roll direction using galvanic
      vestibular stimulation (GVS). Two stance conditions were studied: during forward
      lean posterior compartment muscles are activated and during backward lean
      anterior compartment muscles are activated. GVS-evoked vestibular signals in
      stance control leg muscles as a group: all the active muscles in the leg on the
      GVS cathode side are excited together and those in the contralateral leg (anode
      side) relax. The subject sways towards the anode side. During treadmill walking,
      vestibular actions are subtly different: the actions are largely restricted to
      muscles acting at the ankle joint, occur at longer latencies, are not reciprocal
      in the opposite limb, are modulated throughout the step cycle (largest early in
      stance) and are reversed in sign in the peroneus longus muscle. The subject
      deviates towards the anode side. Hand contact with a firm object reduces GVS
      evoked responses in leg muscles during treadmill walking. Responses to GVS are
      observed during over-ground walking but not significantly during bicycling on an
      ergometer. The observations suggest that these vestibular actions are part of a
      roll stabilisation mechanism. They may be mediated through different spinal
      premotor mechanisms during standing and walking and turned off during bicycling,
      when leg muscles have no balance control function.

PMID- 17031683
TI  - Virtual time-to-contact of postural stability boundaries as a function of support
      surface compliance.
AB  - This study investigated the hypothesis that virtual time-to-contact, which
      specifies the time to reach the functional stability boundary, is a variable
      controlled in the maintenance of upright posture. Three different levels of
      support surface compliance were used on a force platform (no foam, 5 cm of foam,
      and 15 cm of foam). The participant's task was to stand still under each surface
      support condition both with and without vision. The stability boundary was
      determined for each set of conditions where the participant was required to lean
      as far as possible in all directions of the horizontal plane without losing
      stability. The results showed that the no vision conditions had a significantly
      larger center of pressure displacement than the vision conditions. No vision and
      increasing support surface compliance also increased the velocity of the center
      of pressure trajectory. The distribution of the radial displacement of the center
      of pressure showed relatively equal frequency over spatial location with no
      central tendency. The virtual time-to-contact with the stability boundary
      decreased as platform surface support became more compliant. Furthermore, the
      distribution of virtual time over the effective scaling range was a power law
      with a larger exponent in the more unstable no vision and increasing surface foam
      conditions. The findings provide additional evidence for the hypothesis that
      virtual time-to-contact with stability boundaries is a postural control variable
      that is regulated rather than the preservation of minimal motion around the
      center of the stability region as proposed in pendulum models of posture.

PMID- 17031682
TI  - Forces applied by anterior and posterior teeth and roles of periodontal afferents
      during hold-and-split tasks in human subjects.
AB  - Hold-and-split tasks were performed by 20 subjects (12 females and 8 males) using
      the right central incisors, canines, 2nd premolars, and 1st molars, respectively.
      Half a peanut was positioned on a transducer-equipped plate and the subject was
      instructed to hold the plate with the peanut between two antagonistic teeth, and
      not using more force than necessary. After ca. 3 s the subject was instructed to
      split the peanut in a natural manner. Each session consisted of a series of three
      in which the subject performed the hold-and-split task five times for each tooth.
      Thus, in total, data were obtained from 60 trials for each subject. The magnitude
      of the forces and the force rates used to split the peanut increased distally
      along the dental arch. However, the duration of the split phase was similar for
      the various teeth examined. During anesthesia of the periodontal ligament (four
      subjects), no significant changes were seen in the split phase. The forces used
      to hold the peanut between the teeth also increased distally along the dental
      arch: 0.60 N for the incisor, 0.77 N for the canine, 1.15 N for the 2nd premolar,
      and 1.74 N for the 1st molar. The difference in hold forces for the various teeth
      can be explained by the different sensitivity characteristics of the periodontal
      afferents innervating anterior and posterior teeth. During periodontal
      anesthesia, the magnitude and variability of the hold forces increased for all
      types of teeth, thus supporting the suggestion that periodontal afferent
      information is used in the regulation of the level of forces used to hold and
      manipulate morsels between the teeth.

PMID- 17031684
TI  - Inflammation of Hoffa's fat pad in the setting of HIV: magnetic resonance imaging
      findings in six patients.
AB  - OBJECTIVE: To describe MR imaging findings of inflammation of Hoffa's fat pad as
      a cause of nonspecific knee pain in the HIV-infected population. DESIGN:
      Retrospective review. PATIENTS: A retrospective review of 400 consecutive MR
      imaging studies of the knee performed at two institutions over a six-month period
      was conducted. Inclusion criteria included HIV infection in conjunction with
      diffuse high signal intensity throughout Hoffa's fat pad on fluid sensitive
      sequences. Medical histories and images were reviewed by two musculoskeletal
      radiologists. Exclusion criteria included post-surgical changes, internal
      derangement, and/or changes consistent with an active synovial inflammatory
      process. RESULTS: Seven HIV-infected subjects with non-specific knee pain were
      identified, six of whom met imaging inclusion criteria. Findings in Hoffa's fat
      pad were present in nine MR studies (bilateral in three, and unilateral in three
      subjects). Other findings include bilateral enlargement of Hoffa's fat pad in one
      subject, global increase in signal intensity of the suprapatellar fat pad on
      fluid sensitive sequences in three subjects and of the prefemoral fat pad in four
      subjects, avascular necrosis in one subject, and a diffuse pattern of patchy bone
      marrow edema in one subject. Subjects were diagnosed with HIV from 1993-1999,
      with imaging performed in 2005. Subjects were on HAART medication for an
      indeterminate, extended duration of time prior to imaging. CD4 levels of subjects
      ranged from 448-1262 cells/muL (X=727.33 cells/muL). CONCLUSIONS: While the MR
      imaging findings of diffuse inflammation of Hoffa's fat pad are nonspecific and
      unclear in etiology, an association with HIV may exist.

PMID- 17031685
TI  - Severe infectious complications in a patient treated with rituximab for
      idiopathic thrombocytopenic purpura.

PMID- 17031686
TI  - Seizures as an adverse drug reaction after therapeutic dose of vincristine.

PMID- 17031688
TI  - Thrombotic thrombocytopenic purpura as the initial presentation of Pneumocystis
      jiroveci pneumonia in an immunocompetent patient.

PMID- 17031687
TI  - Syndrome of inappropriate secretion of ADH after administration of intrathecal
      chemotherapy in acute promyelocytic leukemia with empty sella of pituitary gland.

PMID- 17031689
TI  - Higher fungal infection rate in elderly patients (more than 80 years old)
      suffering from diffuse large B cell lymphoma and treated with rituximab plus
      CHOP.
AB  - Although adding rituximab to standard cyclophosphamide, doxorubicin, vincristine,
      and prednisone (CHOP) chemotherapy is an efficacious and well-tolerated regimen
      in elderly patients with diffuse large B cell lymphoma (DLBCL), it may increase
      susceptibility to opportunistic infections, and such cases have been reported.
      Our study was to identify the risk factors for fungal infection in a
      retrospective case-control matched study of 34 elderly DLBCL patients treated
      with rituximab plus CHOP (R-CHOP) and 35 control patients treated with the
      standard CHOP regimen at the Taipei Veterans General Hospital, Taiwan. The rate
      of overall infection was similar in both groups. However, subgroup analysis found
      that the fungal infection rate was significantly different, 41.7 and 17.1%, in
      the R-CHOP and CHOP groups, respectively, (P = 0.03). Univariate analysis
      identified the rituximab plus CHOP chemotherapy regimen (P = 0.03), age older
      than 80 years (P = 0.04), and bone marrow involvement (P = 0.04) as risk factors
      for development of fungal infection, whereas, multivariate regression analysis
      identified only rituximab plus CHOP and old age. Adding rituximab to the standard
      CHOP regimen in elderly DLBCL patients might increase the incidence of fungal
      infection especially in those older than 80 years old.

PMID- 17031690
TI  - High-vs low-dose cytarabine combined with interferon alfa in patients with first
      chronic phase chronic myeloid leukemia. A prospective randomized phase III study.
AB  - A prospective randomized phase III study was performed to evaluate whether
      intensified cytarabine would induce a higher response rate and longer event-free
      interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML).
      One hundred and eighteen patients with CML in early chronic phase entered the
      study. Twenty-eight out of 32 patients assigned to group A received two cycles of
      a combination of intensified cytarabine and idarubicin followed by interferon
      alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment
      by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a
      human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell
      transplantation (allo-SCT) and nine patients were excluded from the analysis.
      Hematological response was observed in 97% of the patients in group A vs 86% of
      the patients in group B during the first year of treatment. In group A, 16
      patients (50%) achieved a major cytogenetic response, which compared to seven
      patients (25%) with a major cytogenetic response in group B. With a median follow
      up of 58 months (range 34-76), event-free survival was not significantly
      different between arms A and B. The estimated 5-year survival rate was 56% in the
      intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT
      showed a 5-year estimated survival rate of 55%. Although intensified cytarabine
      induced a higher initial percentage of major and complete cytogenetic responses,
      responses were not sustained by IFN-alpha maintenance therapy.

PMID- 17031691
TI  - Effect of L-carnitine on the physical fitness of thalassemic patients.
AB  - Poor physical fitness is a common problem among thalassemic patients. L-Carnitine
      plays an essential role in fatty acid beta-oxidation, a process especially
      important in the organs that preferentially use fatty acid as a source of energy
      such as the myocardium and the skeletal muscles. The main objective of this study
      is to assess the effect of the administration of oral L-carnitine on exercise
      tolerance and physical fitness in patients with thalassemia major. Thirty
      patients followed up at the New Cairo University Children Hospital were included
      in this study. Clinical, laboratory, and cardiopulmonary exercise testing were
      performed before and after 6 months of oral L-carnitine therapy (50 mg/kg/day).
      The oxygen consumption, cardiac output, and oxygen pulse at maximal exercise
      significantly increased after L-carnitine therapy (p<0.001, p=0.002 and p<0.001,
      respectively). However, there was no significant change in minute ventilation and
      ventilatory equivalent of carbon dioxide (p=0.07 and p=0.06, respectively). A
      weak but positive correlation between the age of the patients and the degree of
      improvement in exercise parameters was noted. There was also significant increase
      in the blood transfusion intervals after L-carnitine administration (p=0.008).
      However, there was no significant change in hemoglobin concentration (p=0.4). L
      Carnitine seems to be a safe and effective adjunctive therapeutic approach in
      thalassemic patients. It improves their cardiac performance and physical fitness.
      The younger the patients are, the higher is the degree of improvement in their
      exercise parameters.

PMID- 17031692
TI  - Hypoxic changes in Purkinje cells of the human cerebellum.
AB  - The significance of both Purkinje cell numbers and various neuronal changes for
      the diagnosis and timing of hypoxic-induced brain lesions was investigated in
      tissue samples from the cerebellar cortex of 52 individuals with a history of
      acute or prolonged cerebral hypoxia/ischemia before death. Furthermore, the area
      of the Purkinje cell somata (PC size) was measured using an automatic image
      processing and analysis system (LEICA QWin). Significantly reduced numbers of
      Purkinje cells (<6 cells/unit length of 1 mm) and a decreased portion (<50%) of
      intact Purkinje cells could be detected in individuals with a period of
      resuscitation of at least 2 h after acute circulatory arrest. Average cell
      numbers of less than 4 cells/unit were found in individuals who suffered from
      diffuse brain swelling and were ventilated for at least 3 days, as well as in
      individuals who died of brain death. Moreover, the Purkinje cells in these cases
      exhibited shrunken somata compared to the controls. Specimens that were stored at
      room temperature up to 30 h after removal at autopsy showed no significant
      autolytic changes of the Purkinje cells. After 46 h, however, reduced Purkinje
      cell numbers and shrunken cell bodies were found.

PMID- 17031693
TI  - Changes in markers of muscle damage, inflammation and HSP70 after an Ironman
      Triathlon race.
AB  - We investigated the effects of an Ironman triathlon race on markers of muscle
      damage, inflammation and heat shock protein 70 (HSP70). Nine well-trained male
      triathletes (mean +/- SD age 34 +/- 5 years; VO(2peak) 66.4 ml kg(-1) min(-1))
      participated in the 2004 Western Australia Ironman triathlon race (3.8 km swim,
      180 km cycle, 42.2 km run). We assessed jump height, muscle strength and
      soreness, and collected venous blood samples 2 days before the race, within 30
      min and 14-20 h after the race. Plasma samples were analysed for muscle proteins,
      acute phase proteins, cytokines, heat shock protein 70 (HSP70), and clinical
      biochemical variables related to dehydration, haemolysis, liver and renal
      functions. Muscular strength and jump height decreased significantly (P < 0.05)
      after the race, whereas muscle soreness and the plasma concentrations of muscle
      proteins increased. The cytokines interleukin (IL)-1 receptor antagonist, IL-6
      and IL-10, and HSP70 increased markedly after the race, while IL-12p40 and
      granulocyte colony-stimulating factor (G-CSF) were also elevated. IL-4, IL-1beta
      and tumour necrosis factor-alpha did not change significantly, despite elevated C
      reactive protein and serum amyloid protein A on the day after the race. Plasma
      creatinine, uric acid and total bilirubin concentrations and gamma-glutamyl
      transferase activity also changed after the race. In conclusion, despite evidence
      of muscle damage and an acute phase response after the race, the pro-inflammatory
      cytokine response was minimal and anti-inflammatory cytokines were induced. HSP70
      is released into the circulation as a function of exercise duration.

PMID- 17031694
TI  - Navigating laparoscopic surgery into the next decade in developing countries - a
      personal perspective.
AB  - INTRODUCTION: Over 500 years ago, Vasco de Gama navigated from west to east, from
      Lisbon in Portugal to Calicut in India, in an epic voyage that lasted over 1 year
      (Fig. 1). This voyage was perhaps the greatest historic and, certainly, the
      greatest navigational achievement of the last millennium. For better or for
      worse, it catalysed a series of events that forever changed not only the history,
      but also the geography of the world. DISCUSSION: In our plans to navigate
      endoscopic surgery into the next decade in developing countries, we too should
      endeavour to change both the history and the geography of surgery. This talk
      traces a journey over 34 years of effort to spread laparoscopic surgery into
      developing countries.

PMID- 17031695
TI  - The effect of NG-nitro L-arginine methyl ester on colonic anastomosis after
      increased intra-abdominal pressure.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (I/R) is associated with augmented
      nitric oxide (NO) production. Increased intra-abdominal pressure (IAP) during
      surgical pneumoperitoneum (P) facilitates I/R injury. We previously demonstrated
      decreased strength and healing of colocolic anastomoses after high IAPs. The
      effect of an NO synthase inhibitor, N (G)-nitro-arginine methyl ester (L: -NAME),
      on anastomoses realized in colonic tissue exposed to high IAPs was investigated
      in this study, a randomized, controlled, and experimental study with blind
      outcome assessment. METHOD: Fifty Wistar-albino rats were randomized to five
      groups; all underwent colocolic anastomosis. P was maintained for 60 min at IAPs
      of 14, 20, 25, and 30 mmHg in study groups 1, 2, 3, and 4, respectively; P was
      preceded by intraperitoneal L: -NAME (2.5 mg/kg) and followed by anastomosis. The
      control group was not subjected to IAP or L: -NAME. RESULTS: Anastomosis bursting
      pressure (ABP) values and histopathological findings were determined on the 7th
      14th postoperative days. The ABPs of groups 3-4 were significantly lower than the
      others. Groups 1-2 had results similar to controls. Histopathological findings of
      the groups were consistent with their ABPs. CONCLUSION: Administration of a 2.5
      mg/kg intraperitoneal L: -NAME dose was found to provide a beneficial role,
      implying a role in impaired anastomotic healing after IAPs of 14 and 20 mmHg.

PMID- 17031696
TI  - Cigarette smoking: cancer risks, carcinogens, and mechanisms.
AB  - BACKGROUND: Cigarette smoking causes about 30% of all cancer mortality in
      developed countries. Although smoking is decreasing in developed countries, it is
      increasing in some developing countries. DISCUSSION: Cigarette smoke contains
      over 60 well established carcinogens. There are strong links between some of
      these carcinogens and various types of smoking-induced cancers. Mechanisms by
      which cigarette smoke carcinogens cause cancer are well established and are
      discussed here. CONCLUSIONS: A great deal is known about cigarette smoke
      carcinogens and the mechanisms by which they cause cancer. It is hoped that this
      will provide new insights for the prevention and cure of tobacco-induced cancer.

PMID- 17031697
TI  - Anthelmintic action of eprinomectin in lactating Anglo-Nubian goats in Brazil.
AB  - Eprinomectin is the only avermectin approved for use to control gastrointestinal
      nematodes in lactating cows. Some studies in the USA and Europe have also
      demonstrated that this drug is highly effective in small ruminants. The aim of
      the present work was to evaluate the anthelmintic efficacy of pour-on
      eprinomectin in Anglo-Nubian goats at the end of lactation. Twenty-four goats
      were used, naturally infected with gastrointestinal nematodes, and divided into
      two groups: control and treated with eprinomectin (Eprinex, Merial, pour-on 0.5%)
      at a dose of 850 microg/kg. Counts were made of the eggs per gram (EPG) of feces,
      along with coprocultures, on days -7, 0, 4, 8, 11, 15, 18, 22, 25 and 29. The
      milk production of each group was recorded throughout the experiment. The
      coprocultures detected 98% Haemonchus contortus and 2% Oesophagostomum. There was
      no statistically significant difference (P > 0.05) in daily milk output between
      the two groups. Eprinomectin at the tested dosage was not effective (P > 0.05) in
      reducing the EPG. Positive results would serve as basis for use of an avermectin
      without residues in dairy goats, providing a scientific basis for greater food
      safety.

PMID- 17031698
TI  - Effect of temperature on the development of Schistosoma japonicum within
      Oncomelania hupensis, and hibernation of O. hupensis.
AB  - The objectives of this investigation were to assess the effect of temperature on
      the development of Schistosoma japonicum harboured in Oncomelania hupensis and to
      determine the lowest temperature threshold at which the hibernation of O.
      hupensis occurs. In the first experiment, adult infection-free O. hupensis,
      collected from Jiangsu province in eastern China, were infected with S. japonicum
      miracidia and raised at different temperatures under laboratory conditions. The
      development of miracidia until the release of cercariae was monitored employing
      the cercarial shedding method. In the second experiment, batches of O. hupensis
      were kept at temperatures below 13 degrees C with the temperature gradually
      reduced. Snail activity was assessed by a pin puncture method. We found a
      positive relationship between the development of S. japonicum within O. hupensis
      and temperature. In snails kept at 15.3 degrees C, S. japonicum arrested their
      development, while the fastest development occurred at 30 degrees C. The
      temperature at which half of the snails were in hibernation (ET(50)) was 6.4
      degrees C. Our results underscore the pivotal role temperature plays on the
      biological activity of O. hupensis and the development of S. japonicum within the
      intermediate host. These findings are likely to have implications for the
      transmission of schistosomiasis in a warmer future China.

PMID- 17031699
TI  - Genotypes and subtypes of Cryptosporidium spp. in neonatal calves in Northern
      Ireland.
AB  - Cryptosporidium spp. in diarrheic calves less than 30 days old from farms across
      Northern Ireland were examined over a year period by microscopic, genotyping, and
      subtyping techniques to characterize the transmission dynamics. Cryptosporidium
      oocysts were detected in 291 of 779 (37.4%) animals. The prevalence rates of
      rotavirus, coronavirus, and Escherichia coli K99+ were lower as seen in 242 of
      806 (30.0%), 46/806 (5.7%), and 16/421 (3.8%) of animals, respectively. Of the
      224 Cryptosporidium-positive specimens available for molecular analysis,
      Cryptosporidium parvum was identified in 213 (95.1%) specimens, Cryptosporidium
      bovis in eight (3.6%), and Cryptosporidium deer-like genotype in three (1.3%).
      Sequence analysis of the 60-kDa glycoprotein gene identified 16 IIa subtypes and
      a new subtype family, with 120 of the 216 (55.6%) positive specimens having the
      subtype IIaA18G3R1. Eight of the IIa subtypes were previously seen in humans in
      Northern Ireland. Several subtypes were temporally or geographically unique. The
      genetic diversity in calves in Northern Ireland was much greater than that
      reported from other areas. This work demonstrates the utility of genotyping and
      subtyping tools in characterizing the transmission of Cryptosporidium spp. in
      calves and humans.

PMID- 17031700
TI  - Effects of the herbivorous minnow, southern redbelly dace (Phoxinus
      erythrogaster), on stream productivity and ecosystem structure.
AB  - We used field and mesocosm experiments to measure effects of southern redbelly
      dace (Phoxinus erythrogaster), a grazing minnow, on stream ecosystem structure
      and function. Ecosystem structure was quantified as algal filament length, algal
      biomass, size distribution of particulate organic matter (POM), algal assemblage
      structure, and invertebrate assemblage structure, whereas ecosystem function was
      based on gross and net primary productivity. Our experiments showed that moderate
      densities of Phoxinus temporarily reduced mean algal filament length and mean
      size of POM relative to fishless controls. However, there was no detectable
      effect on algal biomass or ecosystem primary productivity. Several factors could
      explain the lack of effect of Phoxinus on primary productivity including
      increased algal production efficiency in grazed treatments or increased grazing
      by other organisms in fishless treatments. The inability of Phoxinus to reduce
      algal biomass and system productivity contrasts with experimental results based
      on other grazing minnows, such as the central stoneroller (Campostoma anomalum),
      and questions the generality of grazer effects in stream ecosystems. However,
      environmental venue and the spatial and temporal scale of ecosystem measurements
      can greatly influence the outcome of these experiments.

PMID- 17031701
TI  - How do soil nutrients affect within-plant patterns of herbivory in seedlings of
      Eucalyptus nitens?
AB  - This study assessed how the palatability of leaves of different age classes
      (young, intermediate and older) of Eucalyptus nitens seedlings varied with plant
      nutrient status, based on captive feeding trials with two mammalian herbivores,
      red-bellied pademelons (Thylogale billardierii), and common brushtail possums
      (Trichosurus vulpecula). Seedlings were grown under three nutrient treatments
      (low, medium and high), and we determined how palatability was related to
      chemical and physical characteristics of the leaves. Pademelons ate more older
      leaves than young and intermediate leaves for all treatments. This pattern was
      best explained by sideroxylonals (formylated phloroglucinol compounds known to
      deter herbivory by other marsupials), and/or essential oil compounds that were
      present in lower concentrations in older leaves. In the low-nutrient treatment,
      possums also ate more of the older leaves. However, in the medium- and high
      nutrient treatments, possums ate more intermediate leaves than older leaves and
      showed a behavioural preference for young leaves (consuming younger leaves first)
      over intermediate and older leaves, in spite of high levels of sideroxylonals and
      essential oils. The young leaves did, however, have the highest nitrogen
      concentration of all the leaf age classes. Thus, either sideroxylonals and
      essential oils provided little or no deterrent to possums, or the deterrent was
      outweighed by other factors such as high nitrogen. This study indicates that
      mammalian herbivores show different levels of relative use and damage to leaf age
      classes at varying levels of plant nutrient status and, therefore, their impact
      on plant fitness may vary with environment.

PMID- 17031702
TI  - Pedicle growth asymmetry as a cause of adolescent idiopathic scoliosis: a
      biomechanical study.
AB  - Over the last century the neurocentral junction (NCJ) has been identified as a
      potential cause of adolescent idiopathic scoliosis (AIS). Disparate growth at
      this site has been thought to lead to pedicle asymmetry, which then causes
      vertebral rotation and ultimately, the development of scoliotic curves. The
      objectives of this study are (1) to incorporate pedicle growth and growth
      modulation into an existing finite element model of the thoracic and lumbar spine
      already integrating vertebral body growth and growth modulation; (2) to use the
      model to investigate whether pedicle asymmetry, either alone or combined with
      other deformations, could be involved in scoliosis pathomechanisms. The model was
      personalized to the geometry of a nonpathological subject and used as the
      reference spinal configuration. Asymmetry of pedicle geometry (i.e. initial
      length) and asymmetry of the pedicle growth rate alone or in combination with
      other AIS potential pathogenesis (anterior, lateral, or rotational displacement
      of apical vertebra) were simulated over a period of 24 months. The Cobb angle and
      local scoliotic descriptors (wedging angle, axial rotation) were assessed at each
      monthly growth cycle. Simulations with asymmetrical pedicle geometry did not
      produce significant scoliosis, vertebral rotation, or wedging. Simulations with
      asymmetry of pedicle growth rate did not cause scoliosis independently and did
      not amplify the scoliotic deformity caused by other deformations tested in the
      previous model. The results of this model do not support the hypothesis that
      asymmetrical NCJ growth is a cause of AIS. This concurs with recent animal
      experiments in which NCJ growth was unilaterally restricted and no scoliosis,
      vertebral wedging, or rotation was noted.

PMID- 17031703
TI  - Comment on "A proposal for a surgical classification of pediatric lumbosacral
      spondylolisthesis based on current literature" (Jean-Marc Mac-Thiong, Hubert
      Labelle).

PMID- 17031704
TI  - Tracking the pathway of calcium phosphate/DNA nanoparticles during cell
      transfection by incorporation of red-fluorescing tetramethylrhodamine
      isothiocyanate-bovine serum albumin into these nanoparticles.
AB  - Calcium phosphate nanoparticles were prepared by precipitation from water and
      were then functionalized by DNA. These particles are taken up by living cells and
      function as gene transfer agents, i.e., the DNA is brought into a cell's nucleus
      and is incorporated there into the cell's genome (transfection). DNA which
      encodes for enhanced green fluorescent protein leads to green fluorescence of
      successfully transfected cells. By adding the red-fluorescing marker
      tetramethylrhodamine isothiocyanate-bovine serum albumin (TRITC-BSA) to the
      nanoparticles, their pathway into the cell and within the cell could be followed
      by fluorescence microscopy. A clear correlation between the uptake of
      nanoparticles and the efficiency of transfection was found. Aggregates of
      DNA/TRITC-BSA alone were not able to enter the cells, i.e., the inorganic
      nanoparticles are necessary as a carrier through the cell membrane.

PMID- 17031705
TI  - Pi-pi interaction between aromatic ring and copper-coordinated His81 imidazole
      regulates the blue copper active-site structure.
AB  - Noncovalent weak interactions play important roles in biological systems. In
      particular, such interactions in the second coordination shell of metal ions in
      proteins may modulate the structure and reactivity of the metal ion site in
      functionally significant ways. Recently, pi-pi interactions between metal ion
      coordinated histidine imidazoles and aromatic amino acids have been recognized as
      potentially important contributors to the properties of metal ion sites. In this
      paper we demonstrate that in pseudoazurin (a blue copper protein) the pi-pi
      interaction between a coordinated histidine imidazole ring and the side chains of
      aromatic amino acids in the second coordination sphere, significantly influences
      the properties of the blue copper site. Electronic absorption and electron
      paramagnetic resonance spectra indicate that the blue copper electronic structure
      is perturbed, as is the redox potential, by the introduction of a second
      coordination shell pi-pi interaction. We suggest that the pi-pi interaction with
      the metal ion coordinated histidine imidazole ring modulates the electron
      delocalization in the active site, and that such interactions may be functionally
      important in refining the reactivity of blue copper sites.

PMID- 17031706
TI  - Differences in the cellular mechanism underlying the effects of amphetamine on
      prepulse inhibition in apomorphine-susceptible and apomorphine-unsusceptible
      rats.
AB  - BACKGROUND: Amphetamine is often used to mimic certain aspects of schizophrenia
      in laboratory animals, such as a decreased prepulse inhibition. MATERIALS AND
      METHODS: Apomorphine-susceptible and apomorphine-unsusceptible rats represent a
      well-characterized animal model for individual differences in the sensitivity to
      dopaminergic drugs. Moreover, apomorphine-susceptible rats show a wide variety of
      schizophrenia-like abnormalities. The differential response to administration of
      amphetamine (1-4 mg/kg, i.p.) was investigated in these two rat lines using the
      prepulse inhibition paradigm. Because amphetamine promotes dopamine release, the
      cellular mechanism underlying the line-specific effects of amphetamine was
      investigated by administration of alpha-methyl-para-tyrosine (aMpT) and
      reserpine, substances that are known to deplete the cytosolic dopamine pool and
      the vesicular dopamine pool, respectively, the former being primarily implicated
      in mediating the effects of amphetamine. RESULTS: All doses of amphetamine
      decreased prepulse inhibition in apomorphine-susceptible rats, whereas only the
      highest doses (2 and 4 mg/kg, i.p.) of amphetamine decreased prepulse inhibition
      in apomorphine-unsusceptible rats. Alpha-methyl-para-tyrosine, but not reserpine,
      blocked the amphetamine-induced disruption in prepulse inhibition in apomorphine
      unsusceptible rats, whereas both substances alone had no effect in apomorphine
      susceptible rats. However, the combination of alpha-methyl-para-tyrosine and
      reserpine did block the amphetamine-induced effects in the latter rat line.
      DISCUSSION: The present study suggests that apomorphine-susceptible rats are more
      sensitive to systemic administration of amphetamine than apomorphine
      unsusceptible rats. In addition, the data show that the cellular mechanism
      underlying the effects of amphetamine differs between apomorphine-susceptible and
      apomorphine-unsusceptible rats. Whereas the effects of amphetamine on prepulse
      inhibition in apomorphine-unsusceptible rats just require the alpha-methyl-para
      tyrosine sensitive dopamine pool, the effects in apomorphine-susceptible rats
      require both the alpha-methyl-para-tyrosine sensitive and the reserpine sensitive
      dopamine pool. Because apomorphine-susceptible rats share many features with
      schizophrenic patients, these data open the perspective that in these patients
      amphetamine may induce dopamine release from both types of dopamine pool. This
      might provide an explanation for the increased dopamine release after this
      psychostimulant drug in patients vs controls.

PMID- 17031707
TI  - Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys,
      and humans: areas of agreement, disagreement, and implications for addiction.
AB  - BACKGROUND: Sensitization of mesocorticolimbic dopamine projections has been a
      valuable model of neurobiological adaptation to chronic exposure to cocaine and
      other psychostimulants. DISCUSSIONS: In addition to providing an explanation of
      exaggerated responses to drugs that might explain their increased ability to
      serve as reinforcers, sensitization has also been incorporated into influential
      theories of how drug associated cues can acquire increased salience and incentive
      motivation. However, almost all of the work exploring behavioral and
      neurochemical sensitization has been conducted in rodents. Importantly, the
      relatively small amount of work conducted in human and nonhuman primates differs
      from the rodent work in some important regards. This review will examine areas of
      convergence and divergence between the rodent and primate literature on
      sensitization and the ability of drug associated environmental cues to elicit
      dopamine release. The implications of this comparison for expanding addiction
      research beyond dopaminergic mechanisms in the striatum/nucleus accumbens will be
      considered.

PMID- 17031708
TI  - Adderall produces increased striatal dopamine release and a prolonged time course
      compared to amphetamine isomers.
AB  - RATIONALE: Adderall is currently used for the treatment of Attention-Deficit
      Hyperactivity Disorder (ADHD) and is composed of a novel mixture of approximately
      24% L-amphetamine and 76% D-amphetamine salts. There are, however, no
      investigations of the pharmacological effects of this combination in vivo.
      OBJECTIVES: The technique of high-speed chronoamperometry using Nafion-coated
      single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine
      (DA) release produced by Adderall, D-amphetamine, or D,L-amphetamine in the
      striatum of anesthetized male Fischer 344 (F344) rats. The amphetamine solutions
      were locally applied from micropipettes by pressure ejection. RESULTS: Local
      applications of Adderall resulted in significantly greater DA release signal
      amplitudes with prolonged time course of dopamine release and re-uptake as
      compared to D-amphetamine and D,L-amphetamine. CONCLUSIONS: These data support
      the hypothesis that the combination of amphetamine enantiomers and salts in
      Adderall has effects on DA release, which result in increased and prolonged DA
      release, compared to D- and D,L-amphetamine.

PMID- 17031709
TI  - Effect of paroxetine on enhanced contextual fear induced by single prolonged
      stress in rats.
AB  - RATIONALE: Single prolonged stress (SPS) is an animal model of posttraumatic
      stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal
      negative feedback. OBJECTIVES: We examined whether SPS can produce an enhanced
      psychophysiological reactivity to laboratory stressors unrelated to trauma and
      whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in
      rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was
      examined in rats with and without SPS. METHODS: Rats were subjected to SPS
      (restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept
      undisturbed for 14 days. After that, contextual fear response was assessed.
      Twenty-four hours after foot shock conditioning, freezing behavior was measured
      during reexposure to the shock environment for 3 min. Pain sensitivity was
      assessed by the flinch-jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically
      administered orally in drinking water. RESULTS: Rats subjected to SPS showed a
      significant increase in contextual freezing compared to rats without SPS. Chronic
      administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced
      serum concentrations similar to those that are clinically relevant) caused
      significant suppression of the enhanced contextual freezing. Acute administration
      of PRX at a dose producing clinically relevant serum concentrations did not
      affect the enhanced freezing. CONCLUSIONS: Our results suggest that SPS can
      reproduce behavioral alteration similar to that observed in patients with PTSD,
      and this elevated fear response can be alleviated by the chronic administration
      of PRX at doses producing clinically relevant serum concentrations.

PMID- 17031711
TI  - Tonic dopamine: opportunity costs and the control of response vigor.
AB  - RATIONALE: Dopamine neurotransmission has long been known to exert a powerful
      influence over the vigor, strength, or rate of responding. However, there exists
      no clear understanding of the computational foundation for this effect;
      predominant accounts of dopamine's computational function focus on a role for
      phasic dopamine in controlling the discrete selection between different actions
      and have nothing to say about response vigor or indeed the free-operant tasks in
      which it is typically measured. OBJECTIVES: We seek to accommodate free-operant
      behavioral tasks within the realm of models of optimal control and thereby
      capture how dopaminergic and motivational manipulations affect response vigor.
      METHODS: We construct an average reward reinforcement learning model in which
      subjects choose both which action to perform and also the latency with which to
      perform it. Optimal control balances the costs of acting quickly against the
      benefits of getting reward earlier and thereby chooses a best response latency.
      RESULTS: In this framework, the long-run average rate of reward plays a key role
      as an opportunity cost and mediates motivational influences on rates and vigor of
      responding. We review evidence suggesting that the average reward rate is
      reported by tonic levels of dopamine putatively in the nucleus accumbens.
      CONCLUSIONS: Our extension of reinforcement learning models to free-operant tasks
      unites psychologically and computationally inspired ideas about the role of tonic
      dopamine in striatum, explaining from a normative point of view why higher levels
      of dopamine might be associated with more vigorous responding.

PMID- 17031712
TI  - Infantile hypertrophic pyloric stenosis: an infectious cause?
AB  - The aetiology of infantile hypertrophic pyloric stenosis (IHPS) remains unclear.
      The aim of this study was to test the hypothesis that a common bacterium,
      Helicobacter pylori (HP) may be implicated in the pathogenesis of IHPS. Thirty
      nine consecutive infants with confirmed IHPS had their stool analysed with an
      enzyme immunoassay for the presence of HP. An age/sex-matched group of infants
      with unrelated surgical conditions were also tested. No positive results for the
      presence of HP stool antigen were obtained in the study nor the control group.
      The results of this study demonstrate no causative link between HP and IHPS. A
      genetic basis has been implicated for IHPS. However, evidence does exist that
      IHPS is a condition acquired after birth and that an infective agent may be
      involved in the pathogenesis. Further studies are required to elucidate perinatal
      factors that may induce the expression of this condition in a genetically
      sensitive individual.

PMID- 17031710
TI  - Opioids for hedonic experience and dopamine to get ready for it.
AB  - BACKGROUND AND RATIONALE: More than two decades ago, Wise proposed his "anhedonia
      hypothesis" to explain the role of dopamine in motivated behaviors. The
      hypothesis posits that dopamine mediates the pleasure experienced by reward
      obtainment. However, some experimental findings have contested this hypothesis
      and several authors have proposed alternative functions for dopamine with regard
      to motivation. Brain dopamine has been suggested to rather code for the
      preparatory aspects of behavior, while brain opioids seem to mediate the
      perception of the hedonic properties of rewards. OBJECTIVES: The main goal of
      this review is to reexamine dopamine and opioids involvement in feeding when
      different aspects such as the anticipatory, motivational and consummatory
      components of this behavior are taken into account, but also when the physiologic
      state of the organism and the palatability of the food are considered. RESULTS
      AND CONCLUSIONS: Altogether, the data presented point out for an implication of
      dopamine in the anticipatory/preparatory aspects of feeding more than on the
      motivational and consummatory aspects. However, dopamine involvement in the
      anticipatory/preparatory component of feeding seems specifically related to very
      relevant stimuli, such as highly palatable foods. On the other hand, our data, as
      well as those present in the literature, strongly suggest a role for opioids in
      food intake through their modulation of the hedonic perception of food. As a
      consequence, opioids are involved in those aspects of motivation driven by food
      palatability rather than by food homeostatic need.

PMID- 17031713
TI  - Histological evaluation of the testicular nubbins in patients with nonpalpable
      testis: assessment of etiology and surgical approach.
AB  - There is a controversy in the literature whether testicular nubbins carry
      malignancy risk and excision of the nubbin is necessary in patients with
      nonpalpable testis. It is also controversial whether vanishing testis has the
      same etiopathogenesis and risk with true undescended testis. The aim of this
      study is to investigate the histological findings of testicular nubbins in
      patients with nonpalpable testis and to question etiology and surgical
      indications for vanishing testis. We reviewed the histopathological results of 44
      testicular nubbins in 40 patients (mean age: 4.1 years, range 1-13 years) with
      nonpalpable testis between 1992 and 2004, retrospectively. Exploration revealed 5
      intraabdominal and 39 inguinal testicular nubbins. Of 44 specimens only 5 (11.3%)
      from inquinal testicular nubbins were found to have seminiferous tubules. Two of
      the five had seminiferous tubule structures with viable germ cells showing
      maturation correlating with age. The other two with scarce seminiferous tubules
      were seen on only a single area and one had Sertoli cells only. None of the
      excised tissue had malignant degeneration. The vas deferens was identified in 23
      (52.2%), vessels in 26 (59%), calcification in 14 (31.8%) and hemosiderin in 12
      (27.2%) of excised tissue. Presence of calcification in one-third of the nubbins
      supports vascular accident thesis in the etiopathogenesis of vanishing testis.
      The possibility for the presence of seminiferous tubules and viable germ cells in
      the testicular nubbin is low. These facts decrease theoritical risk of
      malingnancy. Therefore, an inguinal exploration for testicular nubbin in patients
      with vas deferens and vessels entering into the inquinal canal diagnosed at
      laparoscopy can be postponed untill testicular prosthesis implantation and the
      nubbin can be removed at this operation.

PMID- 17031714
TI  - Modulation of respiratory pattern and upper airway muscle activity by the
      pedunculopontine tegmentum: role of NMDA receptors.
AB  - The pedunculopontine tegmental nucleus (PPT) is postulated to have important
      functions relevant to the regulation of rapid eye movement (REM) sleep and
      arousal, and various motor control systems including respiration. We have
      recently shown that pharmacologic activation of a neuronal subpopulation within
      the PPT, induced by micropipette injection of glutamate in nanoliter volumes, can
      produce respiratory rhythm disturbances and changes in genioglossus muscle
      activity in anesthetized rats. The aim of this study was to determine whether the
      respiratory pattern disturbance and increased genioglossus muscle tone induced by
      glutamate injection within the PPT are mediated by activation of N-methyl-D
      aspartate (NMDA) receptors within the PPT. Experiments were performed in eight
      adult male spontaneously breathing Sprague-Dawley rats anesthetized using
      nembutal. Respiratory movements were monitored by piezoelectric strain gauge.
      Three-barrel glass pipettes were used to pressure inject glutamate (as a probe
      for respiratory modulating sites), ketamine (an NMDA channel blocker), and oil
      red dye (to aid in histological verification of the injection sites) within the
      PPT. Electroencephalograms were recorded from the sensorimotor cortex, the
      hippocampus, and the pons, contralateral to the injection site. Electromyograms
      (EMGs) were recorded from the genioglossus muscle. The typical response to
      glutamate injection within the PPT respiratory-modulating region was immediate
      apnea followed by tachypnea and increased genioglossal tonic activity. The
      noncompetitive NMDA receptor channel-antagonist ketamine, injected at the same
      site and in the same volume as glutamate (5 nl), blocked respiratory dysrhythmia
      and genioglossal EMG responses to subsequent glutamate injections. For the first
      time, the present results suggest that respiratory rhythm and upper airway muscle
      tone are controlled by the activation of pedunculopontine tegmental nucleus NMDA
      receptors.

PMID- 17031716
TI  - Performance enhancement for audio-visual speaker identification using dynamic
      facial muscle model.
AB  - Science of human identification using physiological characteristics or biometry
      has been of great concern in security systems. However, robust multimodal
      identification systems based on audio-visual information has not been thoroughly
      investigated yet. Therefore, the aim of this work to propose a model-based
      feature extraction method which employs physiological characteristics of facial
      muscles producing lip movements. This approach adopts the intrinsic properties of
      muscles such as viscosity, elasticity, and mass which are extracted from the
      dynamic lip model. These parameters are exclusively dependent on the neuro
      muscular properties of speaker; consequently, imitation of valid speakers could
      be reduced to a large extent. These parameters are applied to a hidden Markov
      model (HMM) audio-visual identification system. In this work, a combination of
      audio and video features has been employed by adopting a multistream pseudo
      synchronized HMM training method. Noise robust audio features such as Mel
      frequency cepstral coefficients (MFCC), spectral subtraction (SS), and relative
      spectra perceptual linear prediction (J-RASTA-PLP) have been used to evaluate the
      performance of the multimodal system once efficient audio feature extraction
      methods have been utilized. The superior performance of the proposed system is
      demonstrated on a large multispeaker database of continuously spoken digits,
      along with a sentence that is phonetically rich. To evaluate the robustness of
      algorithms, some experiments were performed on genetically identical twins.
      Furthermore, changes in speaker voice were simulated with drug inhalation tests.
      In 3 dB signal to noise ratio (SNR), the dynamic muscle model improved the
      identification rate of the audio-visual system from 91 to 98%. Results on
      identical twins revealed that there was an apparent improvement on the
      performance for the dynamic muscle model-based system, in which the
      identification rate of the audio-visual system was enhanced from 87 to 96%.

PMID- 17031715
TI  - Finite difference and lead field methods in designing implantable ECG monitor.
AB  - To minimize time-consuming and expensive in vitro and in vivo testing,
      information regarding the effects of implantation and the implants on
      measurements should be available during the designing of active implantable
      devices measuring bioelectric signals such as electrocardiograms (ECG). Modeling
      offers a fairly inexpensive and effective means of studying and demonstrating the
      effects of implantation on ECG measurements prior to any in vivo tests, and can
      thus provide the designer with valuable information. Finite difference model
      (FDM) and lead field approaches offer straightforward and effective modeling
      methods supporting the designing of active implantable ECG devices. The present
      study demonstrates such methods in developing and studying ECG implants. They
      were applied in demonstrating the effects of implant dimensions and of electrode
      implantation on the measurement sensitivity of the ECG device. The results of the
      simulations indicated that the interelectrode distance is the factor of the
      implant design determining the lead sensitivity. Other parameters related implant
      dimensions and shape have minor effect on the morphology of the ECG or on the
      average sensitivity of the measurement. This is shown for example when the
      interelectrode distance was reduced to 1/3 of original the average lead
      sensitivity decreased by 69.1% while larger relative changes in other dimensions
      produced clearly smaller changes. It was also observed here that implanting the
      electrodes deeper under the skin has major effects on the local sensitivities in
      heart muscle and thus affect to the morphology of the ECG. The study indicated
      also that non-conducting medium (i.e. implant insulated body) between the
      electrodes increases the sensitivity on heart muscle compared to cases where only
      electrodes are implanted.

PMID- 17031717
TI  - Histopathological workup of an Amplatzer atrial septal defect occluder after
      surgical removal.
AB  - We present results of the histopathological work-up of an atrial septal defect
      occluder that was explanted 15 months after interventional implantation due to a
      significant residual shunt. Complete endothelialization of the surface and a mild
      inflammatory reaction was demonstrated.

PMID- 17031718
TI  - Autologous Ross operation for congenital aortic stenosis.
AB  - Congenital aortic stenosis is a relatively common cardiac anomaly encountered in
      approximately 5% of all children with heart disease. The Ross procedure is
      increasingly used for replacement of the aortic valve in children. We report a 12
      year-old boy who was born with congenital aortic stenosis secondary to a
      bicommissural aortic valve. The patient underwent open valvotomy in infancy and
      aortic valvuloplasty 2 years later. Residual/recurrent stenosis prompted referral
      for aortic valve replacement, and he underwent an autologous Ross procedure, in
      which the aortic root was replaced with a pulmonary autograft and the repaired
      aortic valve was used to restore right ventricular-to-pulmonary artery
      continuity. The postoperative course was unremarkable. Nitroprusside, esmolol,
      and labetolol were used to control postoperative hypertension. He was discharged
      4 days after surgery on oral furosemide and aspirin, and he has had no
      cardiovascular symptoms during follow-up. Recent echocardiography demonstrated
      mild right ventricular outflow tract obstruction with a peak velocity of 3.6
      m/sec, with a gradient of 42 mmHg and moderate pulmonary insufficiency. There was
      no left ventricular outlet tract obstruction or aortic insufficiency.

PMID- 17031719
TI  - Double-orifice mitral valve associated with noncompaction of left ventricular
      myocardium.
AB  - Double-orifice mitral valve (DOMV) is a rare anomaly commonly associated with
      other congenital heart diseases. We present two patients with DOMV and
      noncompaction of the left ventricular myocardium (NLVM). Case 1 was a 5-year-old
      male diagnosed with dilated cardiomyopathy. His echocardiogram showed thin
      myocardium with dilatation at the basal of the left ventricle, thick noncompacted
      myocardium around the apex of the left ventricle, and DOMV (complete bridge type)
      with mild mitral regurgitation. Case 2 was an 11-year-old male diagnosed with
      complete atrioventricular block. His echocardiogram showed thick noncompacted
      myocardium with mild hypokinesis from the posterior to lateral wall and DOMV
      (complete bridge type) with mild mitral regurgitation. DOMV is commonly
      associated with congenital anomaly and always has an abnormal subvalvar
      apparatus. The mitral valve and its apparatus embryologically originate from the
      endomyocardium, which is thought to be the origin of noncompacted myocardium. We
      speculate that patients with DOMV may have NLVM.

PMID- 17031720
TI  - 1173C>T polymorphism in VKORC1 modulates the required warfarin dose.
AB  - The response to warfarin is highly variable among individuals and such
      variability is likely to have some genetic basis. We evaluted the effect of
      VKORC1 polymorphisms on warfarin response among Japanese, taking advantage of its
      unique population structure in which CYP2C9 *2 and *3 alleles are relatively
      rare. Thirty-one patients (12-34 years old; median, 22) on warfarin were
      recruited from a pediatric cardiology clinic. Genotyping of the C>T polymorphism
      at position 1173 in intron 1 of VKORC1 revealed that 26 patients (84%) were T/T
      homozygotes at nucleotide 1173, whereas 5 (16%) were C/T heterozygotes. Complete
      linkage disequilibrium was observed between the 1173C > T polymorphism and
      another polymorphism, the 3730G > A, in the 3' untranslated region. The C/T
      heterozyogtes at the 1173C > T polymorphism tended to require more warfarin than
      the T/T homozygotes, when adjusted for international normalized ratio (p =
      0.003). Both the 1173C > T polymorphism and the 3730G > A polymorphism are likely
      to be inert from a functional standpoint. Rather, based on the complete linkage
      disequilibrium between 1173C > T and 3730G > A polymorphisms, we suspect that the
      actual change that defines the relative resistance to warfarin may be present in
      the proximity of these two polymorphisms.

PMID- 17031721
TI  - Noninvasive visualization and measurement of middle cardiac vein flow by
      transthoracic Doppler echocardiography.
AB  - Transthoracic Doppler echocardiography offers a noninvasive approach for imaging
      posterior descending coronary artery (PD) running in the posterior longitudinal
      sulcus along the middle cardiac vein (MCV). To evaluate whether the MCV flow
      velocity reserve can reflect the PD flow reserve, 22 children with various heart
      diseases were examined using transthoracic Doppler echocardiography. Introduction
      of a modified transthoracic two chamber view with the transducer rotated
      counterclockwise and angulated posteriorly allows visualization of the MCV and
      PD. Peak systolic flow velocity and average peak systolic flow velocity in the
      MCV and peak diastolic flow velocity and average peak diastolic flow velocity in
      the PD were measured at rest and hyperemic conditions (intravenous administration
      of adenosine of 0.16 mg/kg/min). Coronary flow reserve was defined as the ratio
      of peak hyperemic to basal average peak flow velocity. ATP infusion induced
      significant increases in the peak systolic flow velocity and average peak
      systolic flow velocity in the MCV. The mean MCV flow velocity reserve in the
      patients was 1.94 +/- 0.44. Significant increases in the peak diastolic flow
      velocity and the average peak diastolic flow velocity in the PD were also
      observed during ATP infusion, and the mean PD flow velocity reserve (2.19 +/-
      0.62) was significantly higher than the GCV flow velocity reserve (p < 0.0001).
      There was a good correlation between the MCV flow velocity reserve and PD flow
      velocity reserve (r = 0.86, p < 0.0001). This study demonstrated that it was
      possible to measure the MCV flow velocity and MCV flow velocity reserve in
      pediatric patients by transthoracic Doppler echocardiography. The MCV flow
      reserve correlated highly with the PD flow reserve. However, the degree of the
      MCV flow during hyperemia was less than that of the PD flow. This underestimation
      should be considered when the reactive hyperemic response is evaluated from the
      MCV flow velocity.

PMID- 17031722
TI  - Morbidity and mortality assessment of cytoreductive surgery and perioperative
      intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma--a
      prospective study of 70 consecutive cases.
AB  - BACKGROUND: Although many reports regarding morbidity and mortality of
      cytoreductive surgery plus perioperative intraperitoneal chemotherapy are
      available, there are no prospective data on morbidity and mortality limited to
      patients with diffuse malignant peritoneal mesothelioma (DMPM). METHODS: This
      prospective morbidity and mortality assessment was performed on 70 consecutive
      cytoreductive procedures with perioperative intraperitoneal chemotherapy for
      DMPM. Forty-seven adverse events by eight categories were rated from grades I to
      IV with increasing severity. Grade I morbidity was self-limiting; grade II
      required medical treatments; grade III required an invasive intervention; grade
      IV required returning to the operating room or intensive care management. Risk
      factors for grades III and IV morbidity were determined. RESULTS: The
      perioperative mortality rate was 3%. The grades III and IV morbidity rates were
      27 and 14%, respectively. Primary colonic anastomosis (P = 0.028), more than four
      peritonectomy procedures (P = 0.015), duration of the operation of more than 7 h
      (P = 0.027) were the risk factors for grade IV morbidity. Survival analysis of
      these 70 patients was provided. CONCLUSIONS: The morbidity and mortality results
      for cytoreductive surgery and perioperative intraperitoneal chemotherapy for
      patients with DMPM were within the acceptable range for major gastrointestinal
      surgery. Grade IV morbidity was associated with more extensive cytoreduction.

PMID- 17031723
TI  - Stent-graft repair of peroneal arteriovenous fistula.
AB  - Arteriovenous fistulas (AVFs) are infrequently seen in the civilian health-care
      system; traditionally, these lesions have been treated with ligation, or direct
      surgical repair with concomitant revascularization. We describe a rare case of a
      peroneal AVF treated with a stent-graft.

PMID- 17031724
TI  - Missed total occlusion due to the occipital artery arising from the internal
      carotid artery.
AB  - A 56-year-old man was referred for digital subtraction angiography (DSA) with an
      ultrasound diagnosis of right proximal internal carotid artery (ICA) stenosis for
      possible carotid artery stenting. DSA revealed total occlusion of the ICA and an
      occipital artery arising from the stump and simulating continuation of the ICA.
      An ascending pharyngeal artery also arose from the same occipital artery. This
      case is of interest because this is a rare variation besides being a cause of
      misdiagnosis at carotid ultrasound.

PMID- 17031725
TI  - Spontaneous rupture of the hepatic artery in a patient with type 1
      neurofibromatosis treated by embolization: a case report.
AB  - We report the case of a 48-year-old man with neurofibromatosis presenting with
      sudden-onset abdominal pain, profound hypotension, and a drop in hemoglobin. CT
      scan demonstrated a massive hematoma within the right lobe of the liver with
      rupture into the peritoneal cavity. Angiography demonstrated diffuse
      abnormalities of the hepatic circulation with fusifom, ectatic, and stenotic
      segments. Acute extravasation from a peripheral branch of the right hepatic
      artery was identified and successfully embolized with subsequent hemodynamic
      stabilization of the patient. To the best of our knowledge this is the first case
      report of this kind in a patient with type I neurofibromatosis.

PMID- 17031726
TI  - Iatrogenic aorto-cisterna chyli fistula during percutaneous balloon aortoplasty
      in a patient with Takayasu's arteritis: a case report.
AB  - We present a case of iatrogenic aorto-cisterna chyli fistula that developed
      during percutaneous transluminal aortoplasty in a 16-year old girl with
      Takayasu's arteritis. The aorto-cisterna chyli fistula was angiographically
      confirmed and treated using a stent-graft, which successfully occluded the
      fistula. Her claudication then improved, although follow-up CT angiography at 10
      months revealed mild recurrent aortic stenosis.

PMID- 17031727
TI  - Right gastric artery embolization prior to treatment with yttrium-90
      microspheres.
AB  - PURPOSE: Intra-arterial infusion of yttrium-90 microspheres is a form of
      radiation treatment for unresectable hepatic neoplasms. Misdeposition of
      particles in the gastroduodenal area such as the right gastric artery (RGA) may
      occur with serious consequences. We present a series of patients who underwent a
      detailed vascular study followed by RGA embolization. Special emphasis is placed
      on anatomic variations and technical considerations. METHODS: In a 1 year period,
      27 patients were treated. Initial vascular evaluation was performed, with careful
      attention to anatomic variants or extrahepatic arterial supply, especially to the
      gastroduodenal area. Embolization of such arteries was planned if needed. RGA
      embolization was performed antegradely from the hepatic artery or retrogradely
      via the left gastric artery (LGA). Postprocedural follow-up included clinical
      interview and gastroscopy if necessary. RESULTS: RGA embolization was performed
      in 9 patients presenting with primary (n = 3) or metastatic liver tumors (n = 6).
      Six patients underwent antegrade RGA embolization and 3 had embolization done
      retrogradely via the LGA. Retrograde access was chosen for anatomic reasons. None
      of the patients complained of gastroduodenal symptoms. CONCLUSION: RGA
      embolization can help minimize the gastroduodenal deposition of radioactive
      particles. RGA embolization should routinely be carried out. The procedure can be
      performed, with similar technical success, by both anterograde and retrograde
      approaches.

PMID- 17031728
TI  - Palliative airway stenting performed under radiological guidance and local
      anesthesia.
AB  - PURPOSE: To assess the effectiveness of airway stenting performed exclusively
      under radiological guidance for the palliation of malignant tracheobronchial
      strictures. METHODS: We report our experience in 16 patients with malignant
      tracheobronchial stricture treated by insertion of 20 Ultraflex self-expandable
      metal stents performed under fluoroscopic guidance only. Three patients presented
      dysphagia grade IV due to esophageal malignant infiltration; they therefore
      underwent combined airway and esophageal stenting. All the procedures were
      performed under conscious sedation in the radiological room; average procedure
      time was around 10 min, but the airway impediment never lasted more than 40 sec.
      RESULTS: We obtained an overall technical success in 16 cases (100%) and clinical
      success in 14 patients (88%). All prostheses were successfully placed without
      procedural complications. Rapid clinical improvement with symptom relief and
      normalization of respiratory function was obtained in 14 cases. Two patients died
      within 48 hr from causes unrelated to stent placement. Two cases (13%) of
      migration were observed; they were successfully treated with another stent. Tumor
      overgrowth developed in other 2 patients (13%); however, no further treatment was
      possible because of extensive laryngeal infiltration. CONCLUSIONS:
      Tracheobronchial recanalization with self-expandable metal stents is a safe and
      effective palliative treatment for malignant strictures. Airway stenting
      performed exclusively under fluoroscopic view was rapid and well tolerated.

PMID- 17031729
TI  - Aorta-left renal vein fistula complicating an aortic aneurysm: preoperative and
      postoperative multislice CT findings.
AB  - Fistulas complicating an abdominal aortic aneurysm (AAA) are rare, and fistulas
      involving the left renal vein are particularly uncommon. We highlight here a
      fistula between an infrarenal aortic aneurysm and a retroaortic left renal vein,
      revealed by left flank pain associated with hematuria and acute renal failure.
      The multislice CT angiography performed in this 68-year-old patient revealed
      communication and equal enhancement between the aorta and the left gonadic vein,
      suggesting the presence of a fistula. The three-dimensional VRT reconstructions
      presented in this case were of great value in the preoperative planning, enabling
      immediate visualization of this unusual feature. Alternative diagnoses to
      consider when encountering this clinical presentation are reviewed.

PMID- 17031730
TI  - Interventional treatment of a symptomatic neonatal hepatic cavernous hemangioma
      using the Amplatzer vascular plug.
AB  - Percutaneous intervention is one treatment option for symptomatic hepatic
      hemangioma in infants. We report the case of a newborn (birth weight 4060 g) with
      a large hepatic cavernous hemangioma, which presented early with high cardiac
      output failure due to arteriovenous shunting and signs of incipient Kasabach
      Merritt syndrome. We performed a successful superselective transcatheter coil
      embolization of three feeding arteries on the seventh day of life. Because of
      remaining diffuse very small arteries causing a relevant residual shunt,
      additional occlusion of the three main draining veins was necessary with three
      Amplatzer vascular plugs. Cardiac failure resolved immediately. Without any
      additional therapy the large venous cavities disappeared within the following
      months. The tumor continues to regress in size 8 months after the intervention.

PMID- 17031731
TI  - Leiomyosarcoma of the uterus with intravascular tumor extension and pulmonary
      tumor embolism.
AB  - We report the case of a 48-year-old woman presenting with recurrent uterine
      leiomyosarcoma (LMS) associated with right iliac vein and inferior vena cava
      (IVC) invasion and left lower lobe pulmonary tumor embolus. Because the prognosis
      and treatment differ from that of thrombotic pulmonary emboli, the
      differentiating imaging characteristics of intravascular tumor embolism are
      reviewed. To our knowledge, only two other cases of intravenous uterine
      leiomyosarcomatosis have been described in the existing literature, and this is
      the first reported case of the entity with associated intravascular tumor
      embolism.

PMID- 17031732
TI  - Superior mesenteric artery pseudoaneurysm following pancreaticoduodenectomy:
      management by endovascular stent-graft placement and transluminal thrombin
      injection.
AB  - Superior mesenteric artery (SMA) pseudoaneurysm formation is a rare and
      potentially fatal postoperative complication. Herein we present a case of a large
      post-pancreaticoduodenectomy SMA pseudoaneurysm that required thrombin injection
      after initial stent-graft deployment to accomplish complete pseudoaneurysm
      occlusion.

PMID- 17031733
TI  - A survival analysis of patients with malignant biliary strictures treated by
      percutaneous metallic stenting.
AB  - BACKGROUND: Percutaneous metal stenting is an accepted palliative treatment for
      malignant biliary obstruction. Nevertheless, factors predicting survival are not
      known. METHODS: Seventy-six patients with inoperable malignant biliary
      obstruction were treated with percutaneous placement of metallic stents. Twenty
      patients had non-hilar lesions. Fifty-six patients had hilar lesions classified
      as Bismuth type I (n = 15 patients), type II (n = 26), type III (n = 12), or type
      IV (n = 3 patients). Technical and clinical success rates, complications, and
      long-term outcome were recorded. Clinical success rates, patency, and survival
      rates were compared in patients treated with complete (n = 41) versus partial (n
      = 35) liver parenchyma drainage. Survival was calculated and analyzed for
      potential predictors such as the tumor type, the extent of the disease, the level
      of obstruction, and the post-intervention bilirubin levels. RESULTS: Stenting was
      technically successful in all patients (unilateral drainage in 70 patients,
      bilateral drainage in 6 patients) with an overall significant reduction of the
      post-intervention bilirubin levels (p < 0.001), resulting in a clinical success
      rate of 97.3%. Clinical success rates were similar in patients treated with whole
      liver drainage versus partial liver drainage. Minor and major complications
      occurred in 8% and 15% of patients, respectively. Mean overall primary stent
      patency was 120 days, while the restenosis rate was 12%. Mean overall secondary
      stent patency was 242.2 days. Patency rates were similar in patients with
      complete versus partial liver drainage. Mean overall survival was 142.3 days.
      Survival was similar in the complete and partial drainage groups. The post
      intervention serum bilirubin level was an independent predictor of survival (p <
      0.001). A cut-off point in post-stenting bilirubin levels of 4 mg/dl dichotomized
      patients with good versus poor prognosis. Patient age and Bismuth IV lesions were
      also independent predictors of survival. CONCLUSIONS: Percutaneous metallic
      biliary stenting provides good palliation of malignant jaundice. Partial liver
      drainage achieved results as good as those after complete liver drainage. A serum
      bilirubin level of less than 4 mg/dl after stenting is the most important
      independent predictor of survival, while increasing age and Bismuth IV lesions
      represent dismal prognostic factors.

PMID- 17031734
TI  - Cost and reimbursement for three fibroid treatments: abdominal hysterectomy,
      abdominal myomectomy, and uterine fibroid embolization.
AB  - PURPOSE: To compare costs and reimbursements for three different treatments for
      uterine fibroids. METHODS: Costs and reimbursements were collected and analyzed
      from the Thomas Jefferson University Hospital decision support database from 540
      women who underwent abdominal hysterectomy (n = 299), abdominal myomectomy (n =
      105), or uterine fibroid embolization (UFE) (n = 136) for uterine fibroids during
      2000-2002. We used the chi-square test and ANOVA, followed by Fisher's Least
      Significant Difference test, for statistical analysis. RESULTS: The mean total
      hospital cost (US dollar) for UFE was 2,707 dollars, which was significantly less
      than for hysterectomy (5,707 dollars) or myomectomy (5,676 dollars) (p < 0.05).
      The mean hospital net income (hospital net reimbursement minus total hospital
      cost) for UFE was 57 dollars, which was significantly greater than for
      hysterectomy (-572 dollars) or myomectomy (-715 dollars) (p < 0.05). The mean
      professional (physician) reimbursements for UFE, hysterectomy, and myomectomy
      were 1,306 dollars, 979 dollars, and 1,078 dollars, respectively. CONCLUSION: UFE
      has lower hospital costs and greater hospital net income than abdominal
      hysterectomy or abdominal myomectomy for treating uterine fibroids. UFE may be
      more financially advantageous than hysterectomy or myomectomy for the insurer,
      hospital, and health care system. Costs and reimbursements may vary amongst
      different hospitals and regions.

PMID- 17031735
TI  - Percutaneous retrieval of misplaced intravascular foreign objects with the Dormia
      basket: an effective solution.
AB  - PURPOSE: We report our experience of the retrieval of intravascular foreign body
      objects by the percutaneous use of the Gemini Dormia basket. METHODS: Over a
      period of 2 years we attempted the percutaneous removal of intravascular foreign
      bodies in 26 patients. Twenty-six foreign bodies were removed: 8 intravascular
      stents, 4 embolization coils, 9 guidewires, 1 pacemaker lead, and 4 catheter
      fragments. The percutaneous retrieval was achieved with a combination of guide
      catheters and the Gemini Dormia basket. RESULTS: Percutaneous retrieval was
      successful in 25 of 26 patients (96.2%). It was possible to remove all the
      intravascular foreign bodies with a combination of guide catheters and the Dormia
      basket. No complication occurred during the procedure, and no long-term
      complications were registered during the follow-up period, which ranged from 6
      months to 32 months (mean 22.4 months overall). CONCLUSION: Percutaneous
      retrieval is an effective and safe technique that should be the first choice for
      removal of an intravascular foreign body.

PMID- 17031736
TI  - CT-based evaluation of tumor volume after intra-arterial chemotherapy of locally
      advanced carcinoma of the oral cavity: comparison with clinical remission rates.
AB  - PURPOSE: To assess the volume of locally advanced tumors of the oral cavity and
      the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of
      computed tomography and to compare these data with clinically determined
      treatment response of the same patient population. METHODS: Eighty-eight patients
      with histologically proven, advanced carcinoma of the oral cavity and/or the
      oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with
      cisplatin as part of a multimodal therapeutic regimen, comprising (1) local
      chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after
      the intervention, residual disease was evaluated radiologically by measurement of
      the tumor volume and clinically by inspection and palpation of the primary tumor
      according to WHO criteria. RESULTS: Comparison of treatment response according to
      radiological and clinical criteria respectively revealed complete remission in 5%
      vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs.
      58%, and tumor progression in 5% vs. 2%. CONCLUSION: Radiological volumetry and
      clinical evaluation found comparable response rates after local chemotherapy.
      However, in patients with good response after local treatment, volumetric
      measurement with CT may help to distinguish between partial and complete
      remission. Thus, radiological tumor volumetry provides precise and differentiated
      information about tumor response and should be used as an additional tool in
      treatment monitoring after local chemotherapy.

PMID- 17031737
TI  - Histologic results 1 year after bioprosthetic repair of paraesophageal hernia in
      a canine model.
AB  - BACKGROUND: The use of prosthetic materials for the repair of paraesophageal
      hiatal hernia (PEH) may lead to esophageal stricture and perforation. High
      recurrence rates after primary repair have led surgeons to explore other options,
      including various bioprostheses. However, the long-term effects of these newer
      materials when placed at the esophageal hiatus are unknown. This study assessed
      the anatomic and histologic characteristics 1 year after PEH repair using a U
      shaped configuration of commercially available small intestinal submucosa (SIS)
      mesh in a canine model. METHODS: Six dogs underwent laparoscopic PEH repair with
      SIS mesh 4 weeks after thoracoscopic creation of PEH. When the six dogs were
      sacrificed 12 months later, endoscopy and barium x-ray were performed, and
      biopsies of the esophagus and crura were obtained. RESULTS: The mean weight of
      the dogs 1 year after surgery was identical to their entry weight. No dog had
      gross dysphagia, evidence of esophageal stricture, or reherniation. At sacrifice,
      the biomaterial was not identifiable grossly. Biopsies of the hiatal region
      showed fibrosis as well as muscle fiber proliferation and regeneration. No dog
      had erosion of the mesh into the esophagus. CONCLUSIONS: This reproducible canine
      model of PEH formation and repair did not result in erosion of SIS mesh into the
      esophagus or in stricture formation. Native muscle ingrowth was noted 1 year
      after placement of the biomaterial. According to the findings, SIS may provide a
      scaffold for ingrowth of crural muscle and a durable repair of PEH over the long
      term.

PMID- 17031738
TI  - Laparoscopic partial splenectomy.
AB  - BACKGROUND: The immunologic function of the spleen and its important role in
      immune defense has led to splenic-preserving surgery. This study aimed to
      evaluate whether laparoscopic partial splenectomy is safe. METHODS: Data on
      consecutive patients presenting with localized benign or malignant disease of the
      spleen were included in a prospective database. The surgical technique consisted
      of six steps: patient positioning and trocar placement, mobilization of the
      spleen, vascular dissection, parenchymal resection, sealing/tamponading of the
      transected edge, and removal of the specimen. RESULTS: From 1994 to 2005, 38
      patients underwent laparoscopic partial splenectomy. The indications included
      splenomegaly of unknown origin, splenic cysts, benign tumors (hamartoma), and
      metastasis from ovarian carcinoma and schwannoma. The median operating time was
      110 min (range, 65-148 min). The median length of hospital stay was 5 days
      (range, 4-7 days). There was no postoperative mortality. Postoperative pleural
      effusion occurred in two patients. There were no reoperations. Three patients
      required blood transfusions. CONCLUSION: Laparoscopic partial splenectomy is safe
      for patients with localized benign or malignant disease of the spleen.

PMID- 17031739
TI  - Quantification of process measures in laparoscopic suturing.
AB  - BACKGROUND: Process measures describing the generation of movement are useful for
      evaluation and performance feedback purposes. This study aimed to identify
      process measures that differ between novice and advanced laparoscopists while
      completing a suturing skill. METHODS: A group of junior and a group of senior
      residents and fellows in surgery (n = 6) placed 10 laparoscopic sutures in a
      synthetic model. Process measures were quantified using an opto-electric
      motion/force sensor assembly that recorded: instrument rotation, applied forces,
      time, and time delays between force application and instrument rotation. RESULTS:
      Advanced trainees showed increased instrument rotation, higher peak applied
      force, and faster performance compared to novices (alll p < .01). However, over
      trials, only novices showed adaptations for instrument rotation and total time
      (interactions at p < .01) with no adaptation for the force application. The
      difference between the moments of force application and instrument rotation was
      not sensitive to participant training. CONCLUSIONS: Movement process measures can
      enhance our understanding of early adaptation processes and how such factors
      might be used as feedback to facilitate skill acquisition.

PMID- 17031740
TI  - Conversion rate for laparoscopic cholecystectomy after endoscopic retrograde
      cholangiography in the treatment of choledocholithiasis: does the time interval
      matter?

PMID- 17031741
TI  - Laparoscopic ventral recto(colpo)pexy for rectal prolapse: surgical technique and
      outcome for 109 patients.
AB  - The authors propose a new laparoscopic technique for correction of rectal
      prolapse. The unique feature of this technique is that it avoids any
      posterolateral dissection of the rectum. The mesh is sutured to the anterior
      aspect of the rectum to inhibit intussusception. The technique was applied in 109
      consecutive patients to correct total rectal prolapse. Conversion was needed for
      four patients. No postoperative mortality or major morbidity occurred. Minor
      morbidity was noted for 7% of the patients, and a recurrence rate of 3.66% was
      observed. Because this technique limited the dissection and the subsequent risk
      of autonomic nerve damage, a cure comparable with that resulting from classical
      mesh rectopexy can be anticipated.

PMID- 17031742
TI  - Laparoscopic esophagogastrectomy without thoracic or cervical access for
      adenocarcinoma of the gastroesophageal junction: an Indian experience from a
      tertiary center.
AB  - BACKGROUND: The phenomenal progress of minimally invasive surgery has imparted
      its influence on conventional esophagectomy. Currently, more esophagectomies are
      being performed by laparoscopic and/or thoracoscopic methods. Esophagogastrectomy
      for the adenocarcinoma of the gastroesophageal (GE) junction has been a
      conventional treatment. The literature is limited regarding the laparoscopic
      approach to esophagogastrectomy. The aim of this study was to evaluate the
      outcome of laparoscopic esophagogastrectomy in the management of adenocarcinoma
      of the GE junction. METHODS: From January 1997 to February 2005, laparoscopic
      esophagogastrectomy was performed in 32 patients. Indication for operation was
      adenocarcinoma of the GE junction in all patients. Neo-adjuvant therapy was used
      in two patients (6.88%) only. Initially, our approach to intrathoracic
      anastomosis without thoracic and cervical access was to introduce the anvil of
      circular stapler through minilaparotomy incision (n = 22), but later we switched
      to trans-oral placement of anvil into the distal end of the esophagus (n = 10).
      RESULTS: There were 22 men and 10 women. Median age was 61.8 years (range, 39
      72). There was no conversion. The laparoscopic esophagogastrectomy was completed
      in all patients. The pyloromyotomy and feeding jejunostomy were performed in all
      cases. The median intensive care unit stay was 1 day (range, 1-28); hospital stay
      was 7 days (range, 5-42). Mean estimated blood loss and mean operative time were
      150 ml and 200 min, respectively. At mean follow-up of 14 months (range, 2-40),
      stage-specific survival was similar to that of other series. CONCLUSION: In
      selected cases of adenocarcinoma of the GE junction, laparoscopic
      esophagogastrectomy offers as good as or better results than open operation in
      our institution with extensive advance endoscopic and open experience. This study
      shows that laparoscopic esophagogastrectomy has potential to meet oncologic
      criteria of clearance and provide the benefits of minimally invasive surgery as
      well.

PMID- 17031743
TI  - Total and subtotal laparoscopic gastrectomy for adenocarcinoma.
AB  - BACKGROUND: Laparoscopic gastrectomies are currently performed in many centers,
      but compliance with oncologic requirements still represents a subject open to
      debate. The aim of this work was to compare the short-term and oncologic outcomes
      after laparoscopic and open surgery in gastric adenocarcinoma. METHODS: From June
      2000 through June 2005, 147 patients in our institution underwent gastrectomy by
      open or mininvasive approach for adenocarcinoma. The laparoscopy group included
      48 patients, 29 with early gastric cancer (EGC) and 19 with antral advanced
      gastric cancer (AGC). The short-term results and oncologic data were compared to
      those obtained in 99 patients who underwent open surgery. Survival in the
      laparoscopy group was analyzed. RESULTS: In the laparoscopy group no
      intraoperative complications were observed, and conversion was needed in only one
      patient with a large advanced tumor. Overall, 32 lymph nodes were collected by D2
      dissection, 30 for EGC, 34 for advanced cancers. The resection margin was 6.7 cm
      (range: 4-8 cm). The mean operating time was 240 min (range: 150-360 min), with a
      blood loss of 150 ml on average (range: 70-250 ml). Morbidity included two
      duodenal leaks that healed without reoperation; after enclosing or reinforcing
      the staple line, no further leaking was noted. There was one death from massive
      bleeding in a cirrhotic patient. Ambulation and oral feeding started
      significantly earlier than in open surgery. The mean hospital stay was 10 days
      (range: 7-24 days), significantly shorter than the stay of 18 days after open
      surgery (p < 0.05). All patients treated laparoscopically were alive without
      recurrence at the end of this study. CONCLUSIONS: Short-term results with
      laparoscopic gastrectomy were better than with open surgery in this study.
      Oncologic radicality was a major concern, but in the authors' experience the
      extent of lymphadenectomy was the same as in open surgery. This study suggests
      that laparoscopic gastrectomy in malignancies is a reliable tool and oncologic
      requirements can be warranted.

PMID- 17031744
TI  - Medium- and long-term outcome of laparoscopic redo fundoplication.
AB  - BACKGROUND: For a small subset of patients, laparoscopic fundoplication fails,
      typically resulting in recurrent reflux or severe dysphagia. Although redo
      fundoplications can be performed laparoscopically, few studies have examined
      their long-term efficacy. METHODS: Using a prospectively maintained database, the
      authors identified and contacted 41 patients who had undergone redo laparoscopic
      fundoplications at the University of Washington between 1996 and 2001. The median
      follow-up period was 50 months (range, 20-95 months). Current symptoms were
      compared with those acquired and entered into the authors' database
      preoperatively. Patients also were asked to return for esophageal manometry and
      pH testing. RESULTS: All redo fundoplications were performed laparoscopically.
      There were no conversions. The most common indication for redo fundoplication was
      recurrent reflux. The most common anatomic abnormality was a herniated wrap.
      Heartburn improved in 61%, regurgitation in 69%, and dysphagia in 74% of the
      patients. Complete resolution of these symptoms was achieved, respectively, in
      45%, 41% and 38% of these same patients. Overall, 68% of the patients rated the
      success of the procedure as either "excellent" or "good," and 78% said they were
      happy they chose to have it. For those who underwent reoperation for
      gastroesophageal reflux disease, distal esophageal acid exposure according to 24
      h pH monitoring decreased after redo fundoplication from 15.7% +/- 18.1% to 3.4%
      +/- 3.6% (p = 0.041). CONCLUSION: Although not as successful as primary
      fundoplication, a majority of patients can expect durable improvement in their
      symptoms with a laparoscopic redo fundoplication.

PMID- 17031745
TI  - Deployment and early experience with remote-presence patient care in a community
      hospital.
AB  - BACKGROUND: The introduction of the RP6 (InTouch Health, Santa Barbara, CA, USA)
      remote-presence "robot" appears to offer a useful telemedicine device. The
      authors describe the deployment and early experience with the RP6 in a community
      hospital and provided a live demonstration of the system on April 16, 2005 during
      the Emerging Technologies Session of the 2005 SAGES Meeting in Fort Lauderdale,
      Florida. METHODS: The RP6 is a 5-ft 4-in. tall, 215-pound robot that can be
      remotely controlled from an appropriately configured computer located anywhere on
      the Internet (i.e., on this planet). The system is composed of a control station
      (a computer at the central station), a mechanical robot, a wireless network (at
      the remote facility: the hospital), and a high-speed Internet connection at both
      the remote (hospital) and central locations. The robot itself houses a
      rechargeable power supply. Its hardware and software allows communication over
      the Internet with the central station, interpretation of commands from the
      central station, and conversion of the commands into mechanical and nonmechanical
      actions at the remote location, which are communicated back to the central
      station over the Internet. The RP6 system allows the central party (e.g.,
      physician) to control the movements of the robot itself, see and hear at the
      remote location (hospital), and be seen and heard at the remote location
      (hospital) while not physically there. RESULTS: Deployment of the RP6 system at
      the hospital was accomplished in less than a day. The wireless network at the
      institution was already in place. The control station setup time ranged from 1 to
      4 h and was dependent primarily on the quality of the Internet connection
      (bandwidth) at the remote locations. Patients who visited with the RP6 on their
      discharge day could be discharged more than 4 h earlier than with conventional
      visits, thereby freeing up hospital beds on a busy med-surg floor. Patient visits
      during "off hours" (nights and weekends) were three times more efficient than
      conventional visits during these times (20 min per visit vs 40-min round trip
      travel + 20-min visit). Patients and nursing personnel both expressed tremendous
      satisfaction with the remote-presence interaction. CONCLUSIONS: The authors'
      early experience suggests a significant benefit to patients, hospitals, and
      physicians with the use of RP6. The implications for future development are
      enormous.

PMID- 17031746
TI  - HIDA scan ejection fraction does not predict sphincter of Oddi hypertension or
      clinical outcome in patients with suspected chronic acalculous cholecystitis.
AB  - BACKGROUND: Hepatobiliary iminodiacetic scan with ejection fraction (HIDA EF) is
      used to evaluate chronic acalculous cholecystitis (CAC). A presumed etiology of
      CAC is sphincter of Oddi hypertension (SOH). In this study, we evaluated the
      value of HIDA EF to predict patient response to laparoscopic cholecystectomy and
      to identify SOH. METHODS: A prospective study of 93 patients with biliary pain
      but without gallstones (CAC) who underwent preoperative HIDA EF was conducted. At
      laparoscopic cholecystectomy, transcystic antegrade biliary manometry was
      performed to determine the SO pressure. Patients were evaluated postoperatively
      for response to cholecystectomy. The sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) were calculated. The
      outcomes were compared with the clinical impression. RESULTS: Of the 93 patients
      with both HIDA EF and SOP measurements, 50 had abnormal EF (< 35%); of these, 29
      had SOH (SO pressure > or = 40 mmHg). Of the 43 patients with normal HIDA EF, 30
      had SOH. The sensitivity was 49%, specificity 38%, PPV 58%, and NPV 30%. Eighty
      six of the 93 patients returned for follow-up evaluation. Follow-up ranged from 0
      to 99 months, with a mean of 26.4 months. Overall, 73 patients (85%) improved. Of
      the 46 with abnormal HIDA EF, 42 (91%) improved. Of the 40 patients with normal
      HIDA EF, 31 (77.5%) improved. The sensitivity was 57.7%, specificity 69.2%, PPV
      91.3%, and NPV 22.5%. CONCLUSION: Although the PPV of abnormal HIDA EF is high,
      it is not much better than the clinical impression. The sensitivity and
      specificity are marginal. The NPV is poor. Based on the review of these 93
      patients, HIDA EF is not reliable for identifying CAC. We recommend that patients
      with normal HIDA EF have additional testing or consultation before ruling out
      CAC. HIDA EF does not predict SOH.

PMID- 17031747
TI  - Laparoscopic cholecystectomy for early gallbladder carcinoma: long-term outcome
      in comparison with conventional open cholecystectomy.
AB  - BACKGROUND: The role of laparoscopic surgery for malignant gallbladder tumors
      remains uncertain. This study compared the surgical results of laparoscopic
      versus conventional open cholecystectomy for patients with early-stage
      gallbladder carcinoma and examined the role of laparoscopic surgery for early
      gallbladder carcinomas. METHODS: Data for the treatment of gallbladder carcinomas
      were gathered from Chang Gung Memorial Hospital (Linkou, Taiwan). A retrospective
      analysis of 40 patients with either stage 0 or stage 1 gallbladder carcinoma was
      performed. The patients were categorized into two groups on the basis of
      cholecystectomy procedures. The long-term outcomes for the two groups were
      compared. RESULTS: During the follow-up period, which ranged from 6.5 to 197.6
      months, four patients in the conventional open cholecystectomy group encountered
      tumor recurrence, and one patient in the laparoscopic cholecystectomy group
      experienced distant tumor recurrence (p = 0.216). No local port-site tumor
      recurrence was identified in patients who underwent laparoscopic cholecystectomy.
      The overall 5-year survival rate in this series was 87.1%. A comparison of
      survival rates between the two groups demonstrated no significant difference (p =
      0.340). CONCLUSION: The laparoscopic cholecystectomy procedure did not adversely
      influence the prognosis of patients with early-stage gallbladder carcinomas.
      Furthermore, meticulous removal of gallbladders during laparoscopic surgery, in
      which early gallbladder carcinoma can be managed successfully using laparoscopic
      cholecystectomy, achieved a satisfactory surgical result and a low port-site
      tumor recurrence rate.

PMID- 17031748
TI  - A comparison of the effects of pneumoperitoneum and laparotomy on natural killer
      cell mediated cytotoxicity and Walker tumor growth in Wistar rats.
AB  - BACKGROUND: Surgical stress promotes impaired immunological function, which
      contributes to tumor growth. Natural killer activity (NKA) has a protective role
      in immunity to tumors. So, the aim of this experimental study was to assess tumor
      growth and (NKA) after pneumoperitoneum and laparotomy. METHODS; Sixty male
      Wistar rats were divided into three groups (anesthesia, CO2 pneumoperitoneum and
      laparotomy) plus ten controls. All experimental animals were inoculated
      subcutaneously with 8 x 105 Walker carcinosarcoma 256 cells. Animals were
      sacrificed on 1st(POD1) and 8th (POD8) postoperative day. Tumors were excised and
      weighed. RESULTS: On POD1 all animals had diminished NKA when compared to
      controls; NKA after pneumoperitoneum was significantly greater than after
      laparotomy. On POD8 all animals, except after laparotomy, reached NKA at controls
      levels. Tumor weight was significantly greater after laparotomy when compared to
      pneumoperitoneum. CONCLUSIONS: Pneumoperitoneum causes a less depressed NKA and
      less tumor growth when compared to laparotomy.

PMID- 17031749
TI  - Optimum view distance for laparoscopic surgery.
AB  - BACKGROUND: Proper visualization of the surgical field without fatigue is
      essential in laparoscopic surgery and reduces the risk of iatrogenic injuries.
      One of the important factors influencing visualization is the viewing distance
      between the surgeon and the monitor. This was the subject of the current
      investigation. METHODS: For this study, 14 surgeons participated in experiments
      designed to determine two working distances from a standard 34-cm (14 in.
      diagonal) cathode ray tube (CRT) monitor: (a) the maximum view distance
      permitting small prints of a near vision chart to be identified clearly by sight,
      (b) and the minimum view distance (of a standard resolution chart) just short of
      flicker, image degradation, or both. The range of the monitor optimal working
      distance for laparoscopic surgery was extrapolated from these data sets. RESULTS:
      The maximum view distance allowing identification of detail averaged 221 cm
      (range, 166-302 cm). The mean minimal view distance short of flicker/image
      degradation was 136 cm (range, 102-168 cm). The coefficient of variation for the
      two view distances was almost identical (18% vs 17%, respectively), and a
      frequency histogram confirmed the normality of the two data sets. Thus, for most
      surgeons, the extrapolated monitor view distances for laparoscopic surgery using
      a 14-in. diagonal (34-cm) monitor range from 139 to 303 cm (57-121 in.) for
      maximal distance viewing and from 90 to 182 cm (36-73 in.) for close-up viewing
      (i.e., a monitor optimal working distance ranging from 90 to 303 cm (36-121 in.).
      CONCLUSIONS: For most surgeons operating from a 14-in. diagonal CRT monitor, both
      the maximal and minimal (close-up) view distances are individually variable, but
      the surgeon should never be farther than 3 m (10 ft) or less than 0.9 m (3 ft)
      from the monitor. However, within limits, the maximal view distance increases
      with increasing monitor size. The limit for close-up distance is 0.9 m,
      irrespective of monitor size.

PMID- 17031750
TI  - The long-term follow-up of patients with positive intraoperative cholangiograms
      during laparoscopic cholecystectomy.

PMID- 17031751
TI  - Induction of oxidative stress in erythrocytes of male rats subchronically exposed
      to a mixture of eight metals found as groundwater contaminants in different parts
      of India.
AB  - Exposure of animals and humans to different metal components through contaminated
      drinking water can result in a wide range of adverse clinical conditions.
      Toxicological consequences arising from the concurrent repeated exposure to
      multiple metal contaminants are not known. The purpose of the present study was
      to evaluate the oxidative stress-inducing potential of a mixture of eight metals
      (arsenic, cadmium, lead, mercury, chromium, nickel, manganese, iron),
      representative of groundwater contamination in different areas of India, in
      erythrocytes of male rats subchronically exposed to environmentally relevant
      doses via drinking water. The selection of these metals, as determined by
      literature survey of groundwater contamination in India, was primarily based on
      the frequency of their occurrence and contamination level above World Health
      Organization maximum permissible limit (MPL) in drinking water. Male albino
      Wistar rats were exposed to the metal mixture at 0, 1, 10, and 100 times the mode
      concentrations (the most frequently occurring concentration) of the individual
      metals in drinking water for 90 days. In addition, one group of rats was also
      exposed to the mixture at a concentration equal to the MPL of individual
      components. The oxidative stress in erythrocytes was evaluated by assessing the
      magnitude of malondialdehyde production and reduced glutathione (GSH) content and
      the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase
      (GPx), and glutathione reductase (GR) after 30, 60, and 90 days of exposure. MPL
      and 1x dose levels did not cause any changes. The mixture at 10x and 100x doses
      caused dose- and time-dependent effects. After 30 days, the 10x dose did not
      cause any changes except increase in SOD activity. The 100x dose increased the
      activities of SOD, catalase and GR and the GSH level, but caused no alterations
      in lipid peroxidation (LPO) and GPx activity. After 60 days, the 10x dose did not
      cause any changes. The 100x dose increased LPO and decreased all the antioxidant
      parameters, except GSH. After 90 days, both 10x and 100x levels elevated LPO. The
      10x dose decreased GSH level and activities of SOD and catalase, but not of GPx
      and GR, whereas the 100x dose decreased all the antioxidative systems. Overall,
      the present study demonstrates that the subchronic exposure of male rats to the
      mixture of metals via drinking water results in induction of oxidative stress and
      concomitant reduction in antioxidative defense system in erythrocytes at 10 and
      100 times the mode concentrations of the individual metals in contaminated
      groundwater.

PMID- 17031752
TI  - Response of pepper plants (Capsicum annum L.) on soil amendment by inorganic and
      organic compounds of arsenic.
AB  - The influence of soil contamination by inorganic and organic arsenic compounds on
      uptake, accumulation, and transformation of arsenic in pepper (Capsicum annum L.)
      was investigated in greenhouse pot experiments under controlled conditions.
      Pepper plants were cultivated in substrate amended by aqueous solutions of
      arsenite, arsenate, methylarsonic acid (MA), and dimethylarsinic acid (DMA)
      applied individually into cultivation substrate at concentrations of 15 mg As per
      kg of substrate. The plant availability of the arsenicals increased in the order
      arsenite = arsenate < MA < DMA. The highest arsenic concentrations were found in
      roots followed by stems, leaves, and fruits regardless of arsenic compound
      applied. In the control samples of pepper fruits, As(III), As(V), and DMA were
      present (25%, 37%, and 39% of the water-extractable arsenic). In control stems +
      leaves and roots, As(V) was the major compound (63% and 53% in a phosphate buffer
      extract) followed by As(III) representing 33% and 42%. Additionally, low
      concentrations (not exceeding 5%) of DMA and MA were detected as well. In all the
      soils analyzed after the first harvest of pepper fruits, arsenate was the
      dominating compound followed by arsenite. Methylarsonic acid, methylarsonous
      acid, and DMA were present at varying concentrations depending on the individual
      soil treatments. In the treated plants, the arsenic compounds in plant tissues
      reflected predominantly the extractable portions of arsenic compounds present in
      soil after amendment, and this pattern was more significant in the first part of
      vegetation period. The results confirmed the ability of generative parts of
      plants to accumulate preferably organic arsenic compounds, whereas in the roots
      and aboveground biomass, mainly inorganic arsenic species are present. Evidently,
      the source of soil arsenic contamination affects significantly the extractable
      portions of arsenic compounds in soil and subsequently the distribution of
      arsenic compounds within the plants.

PMID- 17031753
TI  - 2,4-D butoxyethyl ester kinetics in embryos of Xenopus laevis: the role of the
      embryonic jelly coat in reducing chemical absorption.
AB  - The role of the jelly coat in providing a protective barrier to chemical
      absorption was studied using the embryos of the amphibian, Xenopus laevis.
      Embryos with or without a jelly coat were water exposed to the butoxyethyl ester
      of 2,4-dichlorophenoxyacetic acid (2,4-D BEE) and the rates of uptake,
      metabolism, distribution, and excretion were determined. The water uptake
      clearance rates were slower for embryos with a jelly coat (1.5-4.5 ml(water).g
      (embryo) (-1).h(-1) or 0.040-0.022 ml(water).h(-1) per embryo) in comparison to
      dejellied embryos (14-21 ml(water).g (embryo) (-1).h(-1) 0.0066-0.021
      ml(water).h(-1) per embryo). This accounted for the much lower residues in
      embryos with a jelly coat than in dejellied embryos during 8 h of exposure.
      Despite quantitative differences in uptake, once 2,4-D BEE had entered the
      embryos, metabolism and distribution were similar between the two test groups.
      2,4-D BEE was metabolized to 2,4-dichlorophenoxyacetic acid (2,4-D) with half
      lives ranging from 35 to 42 minutes. The radioactive residues, as determined by
      whole body autoradiography, appeared throughout the embryo with a slight
      accumulation in the blastocoel. Furthermore, 35% of the radioactive residues were
      located in the jelly coat and 65% in the developing embryo. Based on a slower 2,4
      D elimination in embryos with a jelly coat, the diffusive properties that
      decreased 2,4-D BEE uptake appeared to similarly decrease elimination of its
      metabolite. The common practice of removing jelly coats prior to embryonic
      amphibian toxicity studies, as in the widely used Frog Embryo Teratogenesis Assay
      Xenopus (FETAX), is discouraged based on the kinetic differences observed in this
      study.

PMID- 17031754
TI  - Impact of waterborne copper on the structure of gills and hepatopancreas and its
      impact on the content of metallothionein in juvenile giant freshwater prawn
      Macrobrachium rosenbergii (Crustacea: Decapoda).
AB  - This study aims to elucidate both the impact of copper on the structure of the
      gills and hepatopancreas and the induction of metallothionein (MT) during
      waterborne copper exposure in juvenile Macrobrachium rosenbergii. Structural
      observations were performed with light microscopy, and the MT titrations were
      performed with the cadmium saturation assay. The structural changes that occurred
      in the gills and hepatopancreas appeared to result from copper accumulation, and
      the degree of damage observed in both tissues was relevant to the elevated
      waterborne copper concentration. Exposure to copper concentrations ranging from
      0.01 mg/L to 0.4 mg/L for 7 days resulted in profound structural changes
      including the accumulation of hemocytes in the hemocoelic space; swelling and
      fusion of the lamellae; abnormal gill tips; and hyperplastic, necrotic, and
      clavate-globate lamellae in the gills. Similarly, hemocytic infiltration in the
      interstitial sinuses, an increased number of hemocytes, thickening and ruptures
      of the basal laminae, and necrosis of the tubules were observed in the
      hepatopancreas. The MT measurements showed no significant differences in MT
      contents between the control group and the group treated with 0.01 mg/L
      waterborne copper. The maximum MT content was observed at the level of 0.4 mg/L
      waterborne copper.

PMID- 17031755
TI  - Oxidative degradation of BPA using TiO2 in water, and transition of estrogenic
      activity in the degradation pathways.
AB  - The oxidative degradation behavior of bisphenol A (BPA) using titanium dioxide
      (TiO(2)) in water was investigated. The main purposes were to clarify the
      relationship with estrogenic activity from the degradation pathways demonstrated
      by oxidation of BPA in water. Approximately 99% of the BPA decomposed within 300
      min, and gas chromatography (GC) mass spectrometry (MS) and liquid chromatography
      (LC) MS analysis revealed many intermediates during the degradation process.
      Intermediates by decomposition of BPA, such as hydroxylated-BPA (OH-BPA),
      carboxylic intermediates, phenolic intermediates, and other intermediates
      produced by the cleavage of a benzene ring were identified and quantified.
      Estrogenic activities of the degradation pathways of the BPA in water were
      assessed by using a constructed yeast two-hybrid assay system for human estrogen
      receptor alpha (hERalpha) and Japanese medaka fish (Oryzias latipes) estrogen
      receptor alpha (medERalpha). Estrogenic activity for hERalpha and medERalpha was
      reduced to less than 20% of the initial activity for BPA after 240 min of UV
      irradiation. However, estrogenic activity for medERalpha was increased by 110%
      from the initial activity for BPA at 60 min of UV irradiation. It was estimated
      that medERalpha assay was more sensitive for BPA and the intermediates than was
      the hERalpha assay. From these findings, we estimate that the intermediates by
      the oxidation of BPA have the behaviors of xenoestrogen to the aquatic wildlife
      in the environment.

PMID- 17031756
TI  - Biosynthetic capacity of rainbow trout (Oncorhynchus mykiss) interrenal tissue
      after cadmium exposure.
AB  - The disruption of endocrine system function in wildlife species, including
      teleosts, by contaminants such as metals is presently of major environmental
      concern. Recently, it has been shown that cadmium (Cd) exposure results in
      significant reductions in corticosteroid secretion by fish interrenal
      steroidogenic cells, likely through an inhibition of intracellular cortisol
      synthesis. In the present study, the effects of CdCl(2) on unstimulated and
      stimulated interrenal steroidogenesis in rainbow trout were examined with the
      intention of furthering an understanding of the site(s) of Cd toxic action.
      CdCl(2) alone reduced cortisol secretion in minced interrenal tissues to 59% and
      55% of control values when exposed to 10 and 100 microM, respectively. Incubation
      of interrenal tissues with 0.01 IU/mL adrenocorticotropic hormone (ACTH), which
      activates rate-limiting steps in steroid synthesis, resulted in significant
      stimulation of steroidogenesis in controls. However, ACTH-stimulated
      steroidogenesis was reduced when tissues were previously incubated with Cd.
      Maximal rates of unstimulated cortisol secretion were achieved by augmentation
      using 5 microM 25-hydroxycholesterol (25-OHC) or 0.8 microL/mL synthetic
      cholesterol [SyntheChol(SC)]. Steroidogenesis augmentation by 25-OHC was
      significantly reduced in tissues incubated with Cd. Interestingly, cortisol
      secretion was significantly higher in SC-augmented tissue exposed to 1 and 10
      microM Cd when compared to augmented control tissues. The results of this study
      show that Cd affects both stimulated and unstimulated steroidogenesis in rainbow
      trout, and that one major site(s) of action of Cd in the cortisol synthesis
      pathway is likely prior to cytochrome P450 side chain cleavage.

PMID- 17031757
TI  - Porcine reproductive and respiratory syndrome virus productively infects monocyte
      derived dendritic cells and compromises their antigen-presenting ability.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that play an important
      role in inducing primary antigen-specific immune responses. However, some viruses
      have evolved to specifically target DC to circumvent the host's immune responses
      for their persistence in the host. Porcine reproductive and respiratory syndrome
      virus (PRRSV) causes a persistent infection in susceptible animals. Although it
      is generally believed that the existence of PRRSV quasispecies is partly
      responsible for the virus persistence, other mechanisms of immune evasion or
      immune suppression may also exist. Here, we studied the role of DC in PRRSV
      persistence and immune suppression. Our results showed that PRRSV underwent a
      productive replication in pig monocyte-derived DC (Mo-DC) as measured by both
      immunofluorescence staining of viral nucleocapsid protein and virus titration
      assays, leading to cell death via both apoptosis and necrosis mechanisms.
      Additionally, PRRSV infection of Mo-DC resulted in reduced expression of MHC
      class I, MHC class II, CD14 and CD11b/c. This was in agreement with the impaired
      mixed lymphocyte reaction of PRRSV-infected Mo-DC compared to that of mock
      infected Mo-DC. We also examined the cytokine profiles of PRRSV-infected Mo-DC
      using a quantitative ELISA method. Results indicated that no apparent change in
      the levels of IL-10, IL-12 and IFN-gamma was detected. Taken together, our data
      demonstrate that PRRSV productively infects Mo-DC and impairs the normal antigen
      presentation ability of Mo-DC by inducing cell death, down-regulating the
      expression of MHC class I, MHC class II, CD11b/c and CD14 and by inducing minimal
      Th1 cytokines.

PMID- 17031758
TI  - Effects of pravastatin on ventricular remodeling by activation of myocardial KATP
      channels in infarcted rats: role of 70-kDa S6 kinase.
AB  - Reactive cardiomyocyte hypertrophy after myocardial infarction is an important
      risk factor for arrhythmias. Myocardial ATP-sensitive potassium (K(ATP)) channels
      have been implicated in attenuating cardiac hypertrophy by inhibition of 70-kDa
      S6 kinase. We investigated the effect of pravastatin on ventricular hypertrophy
      during remodeling after myocardial infarction and whether the attenuated
      hypertrophic effect was via activation of myocardial K(ATP) channels. Twenty-four
      hours after ligation of the anterior descending artery, male Wistar rats were
      randomized to either vehicle, nicorandil (an agonist of K(ATP) channels),
      pravastatin, glibenclamide (an antagonist of K(ATP) channels), or a combination
      of nicorandil and glibenclamide or pravastatin and glibenclamide for 4 weeks.
      Infarct size and mortality were similar among the infarcted groups. Cardiomyocyte
      sizes isolated by enzymatic dissociation after infarction significantly increased
      at the border zone in vehicle-treated infarcted rats compared with sham-operated
      rats. Rats in the nicorandil- and pravastatin-treated groups significantly
      attenuated cardiomyocyte hypertrophy, as compared with the vehicle-treated group.
      Arrhythmic scores during programmed stimulation mirrored those of cardiomyocyte
      hypertrophy. Increased 70-kDa S6 kinase mRNA expression in cardiac remodeling was
      confirmed by reverse transcription-polymerase chain reaction, consistent with the
      results of immunohistochemistry and Western blot for the phosphorylation of 70
      kDa S6 kinase. Nicorandil-induced effects were abolished by administering
      glibenclamide. Similarly, the beneficial effects of pravastatin were abolished by
      administering glibenclamide, implicating K(ATP) channels as the relevant target.
      Activation of K(ATP) channels by pravastatin administration can attenuate
      ventricular remodeling through a S6 kinase-dependent pathway after infarction.

PMID- 17031759
TI  - [Hearing loss -- can heat shock protein 70 be cited as prognostic marker?].

PMID- 17031760
TI  - [Tonsillectomy -- dexamethasone lessens postoperative pain].

PMID- 17031761
TI  - [Problems of hyomandibulopexia in patients with OSAS].
AB  - In cases of obstructive sleep apnea syndrome (OSAS) with intolerance of n-CPAP
      (nasal continuous positive airway pressure) treatment, hyoidthyroidpexia
      (synonym: hyoid suspension) has recently been advocated by some authors as a
      valuable surgical option. Despite a basically positive assessment, there is a
      risk of hindrance to the speaking and swallowing function. Moreover, the thyroid
      cartilage seems to be too weak for fixation of the hyoid with its complex
      muscular attachments. This reduces the likelihood of achieving positive long-term
      results. Considering aspects of preserving laryngeal function, we are reporting
      on 7 patients submitted to a hyomandibulopexia. This intervention counteracts the
      tendency of the tongue base to collapse by ventrolateral traction on the
      hypoglossal muscle via the severed greater horn of the hyoid. We have thus far
      had to correct our surgical procedure three times because of methodological
      problems in the postoperative phase. Specific problems with surgical materials
      like steel wire or Goretex are discussed. In conclusion, we explain why we
      consider a bone anchored Kevlar suture (FASTak of Arthrex) to be suitable for
      this operation. Considering functional aspects, our polysomnographic and
      phoniatric follow-up examinations point to a less traumatic surgical procedure
      with promising treatment results.

PMID- 17031762
TI  - [The rationale for imaging methods in head and neck oncology].

PMID- 17031763
TI  - [Exostosis of the internal auditory canal in a patient with myotonic dystrophy].
AB  - A 53-year-old patient with myotonic dystrophy presented to our clinic with
      progressive bilateral hearing loss. The ENT status and particularly the
      otological examination were without pathological signs. Pure tone audiograms
      showed a bilateral moderate to severe sensorineural hearing loss. Routinely
      performed computed tomography of the temporal bones revealed the rare picture of
      exostosis of the internal auditory canals and the medial surface of the petrous
      bones. To our knowledge, this is the first report describing exostosis of the
      internal auditory canal in a patient with myotonic dystrophy, although at present
      it remains unclear in how far there is a causal connection between these two
      pathologies.

PMID- 17031764
TI  - [Malignant external otitis].
AB  - Malignant external otitis or skull base osteomyelitis and osteoradionecrosis of
      the skull base and the skull are potentially life-threatening conditions. The
      standard methods of treatment involve the use of antibiotics, local treatment
      and, where necessary, surgical excision of necrotic tissue. These approaches do
      not provide a complete cure in many cases. Severe functional deficits and even
      death can occur in advanced stages. We conducted a long-term retrospective follow
      up study and report on a multimodal approach that we have been using with great
      success since 1987. The four cornerstones of this treatment are surgical
      debridement, combinations of antibiotics, specific immunoglobulins, and
      adjunctive hyperbaric oxygen therapy. This multimodal treatment approach has
      proved to be highly effective in improving the survival and quality of life of
      the patients concerned. These excellent outcomes justify the high costs that this
      therapy admittedly involves.

PMID- 17031765
TI  - [Standardization of the German short version of "profile of mood states" (POMS)
      in a representative sample--short communication].
AB  - The questionnaire "Profile of Mood States (POMS)" is recommended as a measure of
      mood states in patients and non-clinical samples. On the basis of a
      representative sample (2043 subjects) reference values for the four scales
      (DEPRESSION/ANXIETY, FATIGUE, VIGOR, ANGER) of the German short version of the
      "Profile of Mood States" (POMS--35 items, 7 point scale, instruction "How you
      have been feeling during the past 24 hours?") are presented. The scale ANGER was
      independent from variables gender, age, education and current residence. In
      contrast to the other three scales these differentiations were necessary and
      detailed reference values are reported.

PMID- 17031766
TI  - [Gender mainstreaming: relevance for psychotherapeutic research and practice].

PMID- 17031767
TI  - [Effects of psychosomatic interventions within the consultation service of a
      gynecological university hospital].
AB  - The influence of psychotherapeutic interventions on the long-term course of
      anxiety and depression of inpatients of a Gynaecological University Hospital was
      examined in a prospective naturalistic provision study. All patients admitted to
      hospital within a year were examined regarding anxiety and depression (HADS). The
      patients who had conspicuous values in their questionnaires were randomly
      assigned to an intervention or a control group. There was a follow-up examination
      for them one year after the first examination. In the first examination 715
      participants took part, in the follow-up examination there were 429. Women with
      malignant gynaecological diseases suffer more severely from anxiety (t=7.02;
      p<0.001) and depression (t=3.87; p<0.001) in comparison with the normal
      population. Women suffering from general gynaecological (t=7.75; p<0.001) and
      obstetrical diseases (t=5.95; p<0.001) are significantly more anxious. Whereas
      the anxiety in patients with general gynaecological (F=3.02; p=0.031) as well as
      in patients with obstetrical diseases (F=3.52; p=0.017) can be reduced
      significantly in the long-term by psychotherapeutic interventions, depression
      cannot or only slightly be influenced. This shows that low-frequent
      psychotherapeutic interventions with psycho-educative, supportive approaches (e.
      g. in the framework of psychosomatic consultation and liaison service) have
      positive effects on anxiety in the long run, whereas depression is to be
      influenced rather by long-term interventions or classic depth-psychological or
      behaviour therapeutic interventions.

PMID- 17031768
TI  - [The influence of psychiatric comorbidity on the length of hospital stay of
      medical inpatients within the German Diagnosis Related Groups System].
AB  - The influence of psychiatric comorbidity (ICD-10 categories F1, F3, F4 and F5) on
      the length of hospital stay of 4936 medical inpatients of two medical departments
      of a hospital of tertiary care level was studied. In 994/4936 patients (20.2%) at
      least one F (1,3,4,5)-diagnosis had been coded. 160/994 patients (16.1%) had
      undergone psychosomatic consultation (CL) service treatment. The median of the
      time of from admission until first contact with CL-service was 3 days. Patients
      with psychiatric comorbidity had a significant longer hospital stay (median stay
      without CL-service 5 days, with CL-service 8 days) than patients with no F
      diagnoses coded (4 days) (p<0.01). There were no differences as to patient
      complication and complexity level PCCL between the three groups. Even within a
      diagnosis related groups system psychiatric comorbidity has a negative effect on
      the length of hospital stay.

PMID- 17031769
TI  - [Changes in alexithymia and emotional awareness during psychotherapeutic
      inpatient treatment].
AB  - The aim of the study was to investigate whether alexithymia and emotional
      awareness could be improved by psychotherapeutic inpatient treatment. The role of
      alexithymia and emotional awareness in predicting the treatment outcome was
      investigated. 48 psychosomatically ill patients completed German versions of the
      Toronto Alexithymia Scale (TAS-20), the Levels of Emotional Awareness Scale
      (LEAS), the Symptom Check List (SCL-90-R), the Global Assessment Scale of
      Function (GAF) and the "Beeintrachtigungs-Schwere-Score" (BSS) to assess the
      severity of patient psychological impairment. Psychotherapeutic inpatient
      treatment was associated with a decrease in alexithymia as measured by TAS-20.
      The expected improvement of emotional awareness failed to be statistically
      significant. This may be due to the smaller retest reliability of the LEAS. High
      scores in emotional awareness before therapy as measured by LEAS emerged as a
      predictor of successful psychotherapy with respect to GAF.

PMID- 17031770
TI  - [Depersonalization, social phobia and shame].
AB  - Associations between depersonalization (DP) and social phobia (SP) were described
      in the early scientific literature. This connection, however, has not yet been
      considered in the recent empirical literature and clinical trials on SP. The aim
      of this study is to examine these associations. In a sample of 100 consecutive
      inpatients we compare 45 patients with pathological DP to 55 patients without
      pathological DP with respect to comorbidity and the degree of social anxieties
      assessed with the SOCIAL INTERACTION ANXIETY SCALE (SIAS) and with the SOCIAL
      PHOBIA SCALE (SPS) and the extent of shame assessed with the INTERNALIZED SHAME
      SCALE (ISS). Social phobia was significantly more prevalent in the patients with
      pathological DP. Furthermore, the patients with pathological DP showed a
      significantly larger extent of social anxieties (SIAS, SPS) and shame (ISS). The
      results may be considered as a preliminary empirical support of the assumed
      associations and thus warrant an enhanced consideration of DP in therapy and
      research of social anxiety disorders.

PMID- 17031771
TI  - [Has the translation process impact on the psychometric structure of a
      questionnaire?].
AB  - Little is known about the impact of item translation on the psychometric
      structure of questionnaires. The analysis of different translation versions
      within the same language provides an opportunity to address this question.
      Therefore, in the present study, two of the six available German translations of
      Eating Disorder Inventory (EDI) were compared with respect to their psychometric
      structure. A total of 449 female students completed the short forms of the EDI
      (consisting of the subscales drive for thinness, bulimia and body
      dissatisfaction). Structural equation modeling revealed that the item contents in
      both translations had been interpreted equivalently by the participants. In
      addition, the structural relations among the factors were equivalent across both
      versions. Whereas invariance of item-pair reliability was not tenable, the
      distribution of raw scores of the scales was similar. All in all, the findings
      suggest a very large degree of similarity in the psychometric structure of the
      alternative translations of the EDI versions. The results are discussed with
      respect to the lack of standards for the translation of questionnaires.

PMID- 17031772
TI  - [Development and psychometric evaluation of the "Freiburg questionnaire--stages
      of change in tinnitus" (FQ-STATI)].
AB  - This study describes the psychometric development of an instrument to measure the
      "stages of change" in tinnitus sufferers. Based on our own previous work about
      measuring stages of change in chronic pain patients, 48 items were administered
      to 128 tinnitus sufferers in inpatient and outpatient facilities as well as in
      self helping groups. Principle component analysis and item analysis led to a four
      factor solution. Each factor (resp. stage) consisted of four items:
      precontemplation, preparation, action, and termination. Scales showed
      theoretically conformed associations with measure of pain burden e. g. tinnitus
      loudness and cumbersomeness as well with standardized measures (HADS, TB-12, SF
      12). High burden was correlated positively with high expressions on the lower
      scales, and it was correlated negatively with higher stage scores. Against the
      assumption there was no association between tinnitus durability and stages
      expression.

PMID- 17031773
TI  - [Readiness for behavioural change in somatoform disorders].
AB  - The readiness for behavioural change in patients with somatoform symptoms
      constitutes an important construct in psychotherapy research. However, no
      psychometric instrument is available yet for assessing this construct. This
      study, therefore, attempts to adapt a questionnaire for the assessment of the
      "readiness for behavioural change" in patients with chronic pain (FQ-STAPM) to
      patients with somatoform symptoms. Various psychometric test criteria of the
      questionnaire are examined. The sample consists of n=103 in- and outpatients with
      multiple somatoform symptoms. Item characteristics, reliability (internal
      consistency), and construct validity for three of the four adapted scales are
      acceptable. Furthermore, the four-factor-structure of the FQ-STAPM can be
      confirmed. Moderate changes on the adapted scales of the FQ-STAPM are detected in
      a longitudinal design. The results corroborate the applicability of the
      instrument in patients with somatoform symptoms.

PMID- 17031774
TI  - [The predictive quality of the Psychopathy Checklist-Revised (PCL-R) for violent
      and sex offenders in Switzerland. A validation study].
AB  - In Switzerland, the Hare Psychopathy Checklist-Revised (PCL-R) is administered
      rather restrictively for risk assessment of recidivism among violent and sexual
      offenders. The aim of the present study was a first-time evaluation of the
      predictive validity of the PCL-R for violent and sexual recidivism in
      Switzerland. The PCL-R scores of 96 violent and sex offenders were evaluated by
      collecting the data in their psychiatric expert opinions. The scores were then
      compared to the rates of recidivism as shown in the criminal records. Consistent
      with previous studies in North America and Europe, the determined predictive
      accuracy was satisfying. This degree of precision supports the use of the PCL-R
      for risk assessment of sexual and violent recidivism in Switzerland, as long as
      the instrument does not constitute the sole criterion to determine future
      recidivism, but is applied only in combination with a thorough clinical
      evaluation. The use of precise cut-off scores did not prove to be a valid
      criterion for the prognosis of recidivism and can therefore not be recommended
      for Swiss offenders.

PMID- 17031776
TI  - [Selective serotonine reuptake inhibitors (SSRI) in the treatment of paraphilia].
AB  - For about 15 years selective serotonine reuptake inhibitors (SSRI) have been used
      in the treatment of paraphilias. In an open, uncontrolled, retrospective study,
      which was the first in the German speaking countries we investigated 16 male
      outpatients, who have been treated for different paraphilias with SSRI and
      psychotherapy. There was a marked reduction in paraphilic symptoms. Despite high
      rates of sexual side effects most patients reported a high overall treatment
      satisfaction. SSRI are an important addition in pharmacological treatment of
      paraphilic patients, especially with a risk of so called "hands-off" delinquency.

PMID- 17031775
TI  - [Mixed episodes in bipolar disorder: a review].
AB  - Affective mixed states in bipolar disorders are a current matter of scientific
      debate and represent a complex clinical picture with coexisting manic and
      depressive symptoms. Treatment of mixed states is regarded as an important
      challenge. As diagnostic uncertainties complicate systematic clinical evaluations
      of this patient group, generally accepted clinical treatment guidelines are
      lacking yet. In this review the significance as well as the problems and risks of
      new treatment options are discussed.

PMID- 17031777
TI  - [Neurobiological mechanisms and pharmacological treatment options for alcohol
      craving].
AB  - In the last years, numerous studies have been performed on neurobiological
      mechanisms in alcohol craving. Changes in the hypothalamic cortisol pathway and
      the leptin metabolism, which is also associated with pharmacological
      interventions, have been of special interest. With acamprosate and naltrexone two
      substances exist for pharmacotherapy, but recent results about the efficacy are
      controversial. The clinical profit of disulfiram has been shown, at least in a
      subgroup of patients. Besides, there are several promising candidate substances.
      Current investigations focus on a differentiated pharmacotherapy of alcohol
      dependence, including psychological and genetic factors.

PMID- 17031778
TI  - [Psychiatric expert opinion in case of early retirement--how reliable?].
AB  - The study provides first data on reliability of expert psychiatric opinion under
      regulations of the German state run pension scheme. 22 experienced psychiatrists
      judged very heterogeneously on a hypothetical case suffering from recurrent
      depression of moderate severity. Diagnosis according to ICD-10 led to six
      different diagnoses. 32 % produced the most probable ICD-10 diagnosis, 86 % a
      second diagnosis and 32 % a third. In their final socio-medical verdict eight
      experts found an early retirement on medical grounds to be unjustified, four
      experts thought the insured member incapable of working at all and ten believed
      she was able to work 4-6 hours a day. Contrary to wide held believes concerning
      "lax" psychiatric experts our sample revealed the experts to be "tough". This
      high variability of expert opinions is, however, unacceptable for members of the
      German state-run pensions schemes.

PMID- 17031779
TI  - Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected
      ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis
      of SARS.
AB  - The authors have previously shown that acute lung injury (ALI) produces a wide
      spectrum of pathological processes in patients who die of severe acute
      respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV)
      nucleoprotein is detectable in the lungs, and other organs and tissues, in these
      patients. In the present study, immunohistochemistry (IHC) and in situ
      hybridization (ISH) assays were used to analyse the expression of angiotensin
      converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory
      cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in
      autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its
      RNA were only detected in ACE2+ cells in the lungs and other organs, indicating
      that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo
      in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+
      cells, but not in the uninfected cells. These results suggest that cells infected
      by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated
      damage to the lungs and other organs, resulting in ALI and, subsequently, multi
      organ dysfunction. Therefore application of PIC antagonists may reduce the
      severity and mortality of SARS.

PMID- 17031780
TI  - Risk adjusted resource utilization for AMI patients treated in Japanese
      hospitals.
AB  - Though risk adjustment is necessary in order to make equitable comparisons of
      resource utilization in the treatment of acute myocardial infarction patients,
      there is little in the literature that can be practically applied without access
      to clinical records or specialized registries. The aim of this study is to show
      that effective models of resource utilization can be developed based on
      administrative data, and to demonstrate a practical application of the same
      models by comparing the risk-adjusted performance of the hospitals in our
      dataset. The study sample included 1748 AMI cases discharged from 10 large,
      private teaching hospitals in Japan, between 10 April 2001 and 30 June 2004.
      Explanatory variables included procedures (CABG and PCI), length of stay,
      outcome, patient demographics, diagnosis and comorbidity status. Multiple linear
      regression models constructed for the study were able to account for 66.5, 27.7,
      and 58.4% of observed variation in total charges, length of stay and charges per
      day, respectively. The performance of models constructed for this study was
      comparable to or better than performance reported by other studies that made use
      of explanatory variables extracted from clinical data. The use of administrative
      data in risk adjustment makes broad scale application of risk adjustment
      feasible.

PMID- 17031781
TI  - The economic cost of teen drinking: late graduation and lowered earnings.
AB  - This paper analyzes the effect that binge drinking has on the probability of
      graduating on time from high school and on future earnings. The analysis is
      conducted on students in their senior year of high school using data from the
      National Longitudinal Survey of Youth 1979. Importantly, the usual instruments
      used to correct for the endogeneity of the drinking variable are found to be
      robust only for women. This paper finds that heavy drinking decreases the
      probability of graduating on time. Binge drinking does not have a direct impact
      on adults' labor earnings, but graduating late results in lower labor income.
      Because of a late graduation, young men who binge in high school will face an
      earnings penalty of 1.5-1.84 percentage points. Women also face a penalty, but
      this seems mostly due to the fact that women who graduate late work in industries
      and occupations that pay less.

PMID- 17031782
TI  - Consolidations and closures: an empirical analysis of exits from the hospital
      industry.
AB  - This paper investigates the pre-exit characteristics of hospital mergers,
      acquisitions, and closures. We estimate competing risk hazard models using an 18
      year national data set that spans the wave of closures in the 1980s and of
      mergers in the 1990s. Evidence shows that weak productivity of the hospital is a
      strong determinant for closures while competitive pressures are more influential
      in the decision to consolidate. Thus, increased market power, relative to cost
      reductions, appears to play a larger role in the merger decision. Our results
      also provide insight into possible correlations between mergers and closures.

PMID- 17031784
TI  - What is the future of electrophoresis in large-scale genomic sequencing?
AB  - Although a finished human genome reference sequence is now available, the ability
      to sequence large, complex genomes remains critically important for researchers
      in the biological sciences, and in particular, continued human genomic sequence
      determination will ultimately help to realize the promise of medical care
      tailored to an individual's unique genetic identity. Many new technologies are
      being developed to decrease the costs and to dramatically increase the data
      acquisition rate of such sequencing projects. These new sequencing approaches
      include Sanger reaction-based technologies that have electrophoresis as the final
      separation step as well as those that use completely novel, nonelectrophoretic
      methods to generate sequence data. In this review, we discuss the various
      advances in sequencing technologies and evaluate the current limitations of novel
      methods that currently preclude their complete acceptance in large-scale
      sequencing projects. Our primary goal is to analyze and predict the continuing
      role of electrophoresis in large-scale DNA sequencing, both in the near and
      longer term.

PMID- 17031786
TI  - Microchips and single-photon avalanche diodes for DNA separation with high
      sensitivity.
AB  - Modern techniques for DNA and protein analysis and separation rely on
      measurements of LIF and face a trend toward employing progressively smaller
      samples. The currently employed detectors that provide the required ultrahigh
      sensitivity, e.g. photomultiplier tubes (PMTs), are bulky and/or costly and
      delicate, whereas a key issue for the development of compact and economical
      instruments is the availability of miniaturized, inexpensive, and ultrasensitive
      photodetectors. The planar epitaxial silicon single-photon avalanche diodes
      (SPADs) combine the typical advantages of microelectronics (miniaturization,
      ruggedness, low voltage, low power, low cost, etc.) with high sensitivity, even
      better than that of PMTs. The suitability of such SPADs to microchip CE has been
      here ascertained by developing a new apparatus with dual-wavelength LIF
      detection. The apparatus has been experimented in studies on the EOF suppression
      and on the coating stability and tested in rapid sizing of DNA fragments. The
      experimental results obtained in the separation of Cy5-labeled oligonucleotide
      demonstrate sensitivity better than 3 pM, which corresponds to less than 100
      fluorescent molecules in the 50 pL illuminated volume.

PMID- 17031787
TI  - The potential of electrophoretic mobility shift assays for clinical mutation
      detection.
AB  - As the understanding of the links between genetic mutations and diseases
      continues to grow, there is an increasing need for techniques that can rapidly,
      inexpensively, and sensitively detect DNA sequence alterations. Typically, such
      analyses are performed on PCR-amplified gene regions. Automated DNA sequencing by
      capillary array electrophoresis can be used, but is expensive to apply to large
      numbers of patient samples and/or large genes, and may not always reveal low
      abundance mutations in heterozygous samples. Many different types of genetic
      differences need to be detected, including single-base substitutions and larger
      sequence alterations such as insertions, deletions, and inversions.
      Electrophoretic mobility shift assays seem well suited to this purpose and could
      be used for the efficient screening of patient samples for sequence alterations,
      effectively reducing the number of samples that must be subjected to full and
      careful sequencing. While there is much promise, many of the mobility shift
      assays presently under development have yet to be demonstrated to have the high
      sensitivity and specificity of mutation detection required for routine clinical
      application. Hence, further studies and optimization are required, in particular
      the application of these methods not only to particular genes but also to large
      numbers of patient samples in blinded studies aimed at the rigorous determination
      of sensitivity and specificity. This review examines the state-of-the-art of the
      most commonly used mobility shift assays for mutation detection, including
      denaturing gradient gel electrophoresis, TGGE, SSCP, heteroduplex analysis, and
      denaturing HPLC.

PMID- 17031791
TI  - Orbitrap mass analyzer--overview and applications in proteomics.
AB  - The orbitrap mass analyzer is proving itself as a useful addition to a proteomics
      tool box. The key attributes of this analyzer are accurate mass and high
      resolution similar to those achievable with FT ICR instrumentation. The basic
      principles underlying these capabilities, and how they translate into benefits in
      real-life proteomics experiments are discussed. The focus is on reviewing
      examples of protein identification with bottom-up and top-down approaches, and
      detection of post-translational modifications.

PMID- 17031793
TI  - Web-based MS/MS data analysis.
AB  - This tutorial focuses on three MS/MS data analysis programs currently available
      via a web interface: Mascot, Phenyx and X!Tandem. Although these programs process
      the same input and often produce comparable outputs, subtle differences remain.
      The use of parameters that are requested in the on-line forms and the subsequent
      interpretation of results are illustrated and explained via a single example.

PMID- 17031794
TI  - The HUPO proteomics standards initiative--overcoming the fragmentation of
      proteomics data.
AB  - Proteomics is a key field of modern biomolecular research, with many small and
      large scale efforts producing a wealth of proteomics data. However, the vast
      majority of this data is never exploited to its full potential. Even in publicly
      funded projects, often the raw data generated in a specific context is analysed,
      conclusions are drawn and published, but little attention is paid to systematic
      documentation, archiving, and public access to the data supporting the scientific
      results. It is often difficult to validate the results stated in a particular
      publication, and even simple global questions like "In which cellular contexts
      has my protein of interest been observed?" can currently not be answered with
      realistic effort, due to a lack of standardised reporting and collection of
      proteomics data. The Proteomics Standards Initiative (PSI), a work group of the
      Human Proteome Organisation (HUPO), defines community standards for data
      representation in proteomics to facilitate systematic data capture, comparison,
      exchange and verification. In this article we provide an overview of PSI
      organisational structure, activities, and current results, as well as ways to get
      involved in the broad-based, open PSI process.

PMID- 17031795
TI  - Minimum reporting requirements for proteomics: a MIAPE primer.
AB  - Amongst other functions, the Human Proteome Organization's Proteomics Standards
      Initiative (HUPO PSI) facilitates the generation by the proteomics community of
      guidelines that specify the appropriate level of detail to provide when
      describing the various components of a proteomics experiment. These guidelines
      are codified as the MIAPE (Minimum Information About a Proteomics Experiment)
      specification, the first modules of which are now finalized. This primer
      describes the structure and scope of MIAPE, places it in context amongst
      reporting specifications for other domains, briefly discusses related informatics
      resources and closes by considering the ramifications for the proteomics
      community.

PMID- 17031796
TI  - Comments on standards in proteomics and the concept of fitness-for-purpose.

PMID- 17031797
TI  - Statistics for proteomics: a review of tools for analyzing experimental data.
AB  - Most proteomics experiments make use of 'high throughput' technologies such as 2
      DE, MS or protein arrays to measure simultaneously the expression levels of
      thousands of proteins. Such experiments yield large, high-dimensional data sets
      which usually reflect not only the biological but also technical and experimental
      factors. Statistical tools are essential for evaluating these data and preventing
      false conclusions. Here, an overview is given of some typical statistical tools
      for proteomics experiments. In particular, we present methods for data
      preprocessing (e.g. calibration, missing values estimation and outlier
      detection), comparison of protein expression in different groups (e.g. detection
      of differentially expressed proteins or classification of new observations) as
      well as the detection of dependencies between proteins (e.g. protein clusters or
      networks). We also discuss questions of sample size planning for some of these
      methods.

PMID- 17031798
TI  - Preparation of plant samples for 2-d electrophoresis.
AB  - Plant protein samples are very difficult to extract and prepare for 2-D
      electrophoresis, because polyphenols can build irreversible complexes with the
      proteins, the protein concentrations are relatively low, polysaccharides and
      lipids can cause severe disturbances in the 2-D gel.

PMID- 17031799
TI  - Analysis of membrane protein complexes by blue native PAGE.
AB  - Blue native polyacryamide gel electrophoresis is a special case of native
      electrophoresis for high resolution separation of enzymatically active protein
      complexes from tissue homogenates and cell fractions. The method is powerful
      between 10 and 10,000 kDa. Also membrane protein complexes are separated well
      after solubilization of complexes with mild neutral detergents. The separation
      principle relies on binding of Coomassie blue G250 which provides negative
      charges to the surface of the protein. During migration to the anode, protein
      complexes are separated according to molecular mass and/or size and high
      resolution is obtained by the decreasing pore size of a polyacrylamide gradient
      gel. The principles of 2-dimensional blue native sodium dodecyl sulfate
      polyacrylamide gel electrophoresis are presented here together with a practical
      step-by-step guide to performing the method in the laboratory.

PMID- 17031800
TI  - Sensitive, quantitative, and fast modifications for Coomassie Blue staining of
      polyacrylamide gels.
AB  - In spite of the high sensitivity of silver staining and the wide dynamic range of
      various fluorescent detection methods, Coomassie Brilliant Blue staining is still
      the most widely used protein detection technique for proteins separated by
      polyacrylamide gel electrophoresis. There are several reasons: Low price, Visible
      with the eye, Desk top scanners can be employed for image acquisition, Better for
      quantitative analysis than silver staining, Possible modifications for fast or
      highly sensitive staining, Mass spectrometry compatible.

PMID- 17031801
TI  - Proteomics success story. Towards early detection of breast and ovarian cancer:
      plasma proteomics as a tool to find novel markers.

PMID- 17031802
TI  - Proteomics success story. Novel biomarkers for DNA damage response pathways:
      insights and applications for cancer therapy.

PMID- 17031803
TI  - Geographical focus. Proteomics initiatives in Spain: ProteoRed.
AB  - The Spanish National Network of Proteomic Facilities--ProteoRed has been created
      as an initiative for the coordination, integration and development of the
      proteomics facilities and laboratories distributed throughout Spain. ProteoRed's
      main objective is to give support to the scientific community allowing them wide
      access to emerging proteomics technologies and thus encouraging the science of
      proteomics. In addition, standardization of protocols and robustness of workflows
      are addressed by multi-centric laboratory activities. Educational, training and
      dissemination issues are part of the core activities of ProteoRed. To reach these
      objectives, specific activities have been developed through six working groups
      (WG1-WG6) covering functional, technical, educational and scientific aspects of
      proteomics.

PMID- 17031804
TI  - Report. Proteomics education, an important challenge for the scientific
      community: report on the activities of the EuPA Education Committee.
AB  - The main missions of the EuPA Education Committee (EuPA-EC) are to promote and
      enhance the quality of proteomics knowledge by creating educational programs and
      to initiate European-wide scientific exchange programs for young proteomics
      researchers. In this first report we present the initial actions we have
      undertaken in relation to the missions of the EuPA-EC, and the educational
      activities that have been planned for 2007-2008. These activities include courses
      (basic and advanced courses and a summer school), workshops, laboratory
      networking and tutorials.

PMID- 17031805
TI  - Random control clinical trial on the effects of aerobic exercise training on
      erythrocyte levels during radiation treatment for breast cancer.
AB  - BACKGROUND: Erythrocyte changes from aerobic exercise training were examined
      during radiation treatment of breast cancer. METHODS: Twenty sedentary females
      with breast carcinoma who were ages 35 to 65 years were randomized to aerobic
      exercise (AE) of walking for 20 to 45 minutes, 3 to 5 times per week, at 50% to
      70% of measured maximum heart rates or to placebo stretching (PS) activities 3 to
      5 days per week during 7 weeks of radiation treatment. Measures were obtained 1
      week before and after the radiation regimen. Serum blood analyses, through
      complete blood counts, measured red blood cell counts (RBC), hematocrit (HCT),
      and hemoglobin (HB). Peak aerobic capacity (peak VO(2)) was measured by exercise
      testing with oxygen uptake analysis to assess training. A Wilcoxon Mann-Whitney U
      test examined changes between groups (P < or = .05 for significance). RESULTS: AE
      peak VO(2) increased by 6.3% (P = .001) and PS decreased by 4.6% (P = .083). RBC
      increased in AE from 4.10 to 4.21 million cells/microL and declined in PS from
      4.30 to 4.19 million cells/microL; the between-group differences were significant
      (P = .014). HCT increased in AE from 38.0% to 38.8% and declined in PS from
      37.40% to 36.50%; the between-group differences were significant (P = .046). HB
      increased in AE from 12.3 to 12.4 g/dL and declined in PS from 12.25 to 11.77
      g/dL; the between-group differences were significant (P = .009). CONCLUSIONS: The
      results of the current study suggest that moderate intensity aerobic exercise
      appears to maintain erythrocyte levels during radiation treatment of breast
      cancer compared with the declines observed in nontraining individuals. These
      findings suggest a safe, economical method to improve fitness and maintain
      erythrocytes in women during radiation treatment of breast cancer.

PMID- 17031806
TI  - Flores hominid: new species or microcephalic dwarf?
AB  - The proposed new hominid "Homo floresiensis" is based on specimens from cave
      deposits on the Indonesian island Flores. The primary evidence, dated at
      approximately 18,000 y, is a skull and partial skeleton of a very small but
      dentally adult individual (LB1). Incomplete specimens are attributed to eight
      additional individuals. Stone tools at the site are also attributed to H.
      floresiensis. The discoverers interpreted H. floresiensis as an insular dwarf
      derived from Homo erectus, but others see LB1 as a small-bodied microcephalic
      Homo sapiens. Study of virtual endocasts, including LB1 and a European
      microcephalic, purportedly excluded microcephaly, but reconsideration reveals
      several problems. The cranial capacity of LB1 ( approximately 400 cc) is smaller
      than in any other known hominid < 3.5 Ma and is far too small to derive from Homo
      erectus by normal dwarfing. By contrast, some associated tools were generated
      with a prepared-core technique previously unknown for H. erectus, including
      bladelets otherwise associated exclusively with H. sapiens. The single European
      microcephalic skull used in comparing virtual endocasts was particularly
      unsuitable. The specimen was a cast, not the original skull (traced to
      Stuttgart), from a 10-year-old child with massive pathology. Moreover, the
      calotte does not fit well with the rest of the cast, probably being a later
      addition of unknown history. Consideration of various forms of human microcephaly
      and of two adult specimens indicates that LB1 could well be a microcephalic Homo
      sapiens. This is the most likely explanation for the incongruous association of a
      small-brained recent hominid with advanced stone tools.

PMID- 17031807
TI  - The anatomical record: a tradition of reporting what is new about things that are
      very, very old.

PMID- 17031808
TI  - Terminal nerve in the mouse-eared bat (Myotis myotis): ontogenetic aspects.
AB  - As in other mammals, ontogenesis of the terminal nerve (TN) in the mouse-eared
      bat (Myotis myotis) starts shortly after the formation of the olfactory placode,
      a derivative of the ectoderm. During development of the olfactory pit,
      proliferating neuroblasts thicken the placodal epithelium and one cell population
      migrates toward the rostroventral tip of the telencephalon. Here they accumulate
      in a primordial terminal ganglion, which successively divides into smaller units.
      Initial fibers of the TN can be distinguished from olfactory fibers in the mid
      embryonic period. The main TN fiber bundle (mfb) originates from the anteriormost
      ganglion in the nasal roof, whereas one or more inconstant smaller fiber bundles
      (sfb) originate from one or more smaller ganglia in the basal part of the rostral
      nasal septum. The fibers of the mfb and sfbs join in the posterior quarter of the
      nasal roof before reaching the central ganglion (M) located in the meninges
      medial to the olfactory bulb. From the mid-fetal period onward, a thin TN fiber
      bundle with some intermingled perikarya connects M to the brain by penetrating
      its wall rostral to the olfactory tubercle. Additional smaller ganglia may occur
      in this region. The TN and its ganglia persist in postnatal and adult bats but
      the number of perikarya is reduced here. Moreover, the different potential
      functions of the TN are discussed briefly.

PMID- 17031809
TI  - Tissue evidence of the testosterone role on the abnormal growth and aging effects
      reversion in the gerbil (Meriones unguiculatus) prostate.
AB  - Prostate differentiation during embryogenesis and its further homeostatic state
      maintenance during adult life depend on androgens. Abundant biological data
      suggest that androgens play an important role in the development of the prostate
      cancer and other prostatic diseases. The objective of this work was to evaluate
      the effects of the testosterone supplementation in gerbil (a new experimental
      model) at different ages. Tissues from experimental animals were studied by
      histological and histochemistry procedures, androgen receptor
      immunohistochemistry assay, morphometric-stereological analysis, and transmission
      electron microscopy (TEM). After the treatment were observed increase of prostate
      weight and epithelium height in all ages studied. In some adult and aged treated
      animals, hyperplasic and dysplastic process were observed, including prostatic
      intraepithelial neoplasias and adenocarcinomas. Increase of the thickness of the
      smooth muscle cell (SMC) layer was observed in pubescent and adult animals and
      TEM revealed apparent SMC hypertrophy. An apparent increase in the frequency of
      blood vessels distributed by the subepithelial stroma in the treated animals was
      noticed. Reversion of the natural effects of aging on the prostate was observed
      in the aged treated animals in some acini of the gland. These data demonstrate
      that the gerbil prostate is susceptible to androgenic action at the studied ages
      and it can serve, for example, as experimental model to studies of prostate
      neoplastic process induction and hormonal therapy in aged animals.

PMID- 17031810
TI  - Three-dimensional myoarchitecture of the bovine tongue demonstrated by diffusion
      spectrum magnetic resonance imaging with tractography.
AB  - The anatomy of the mammalian tongue consists of an intricate array of variably
      aligned and extensively interwoven muscle fibers. As a result, it is particularly
      difficult to resolve the relationship between the tongue's microscopic anatomy
      and tissue-scale mechanical function. In order to address this question, we
      employed a method, diffusion spectrum imaging (DSI) with tractography, for
      displaying the macroscopic orientational properties of the tissue's constituting
      myofibers. DSI measures spatially variant proton displacement for a given 3D
      imaging segment (voxel), reflecting the principal orientation(s) of its
      myofibers. Tractography uses the angular similarity displayed by the principal
      fiber populations of multiple adjacent voxels to generate tract-like structures.
      DSI with tractography thus defines a unique set of tracts based on the net
      orientational behavior of the myofiber populations at different positions in the
      tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the
      bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts
      in the intrinsic core region, and longer, parallel-aligned fiber tracts on the
      tissue margins and in the regions of extrinsic fiber insertion. The
      identification of locally aligned myofiber populations by DSI with tractography
      allows us to reconsider lingual anatomy, not in conventional microscopic terms,
      but as a set of heterogeneously aligned and macroscopically resolved myofiber
      tracts. We postulate that the properties associated with these myofiber tracts
      predict the mechanical behavior of the tissue and thus constitute a method to
      relate structure and function for anatomically complex muscular tissues.

PMID- 17031811
TI  - Endochondral ossification of the mouse nasal septum.
AB  - Endochondral ossification at the caudal junctions of the cartilaginous nasal
      septum, in combination with interstitial expansion of the septum, is thought to
      displace the facial skeleton away from the neurocranium. However, the rate of
      endochondral ossification has not been measured or related to rates of septal
      enlargement. This study examined endochondral ossification at these junctions in
      mice from postnatal days 0-15, in the context of known cranial growth sites, the
      synchondroses. BrdU labeling was used to compare cell division at the
      septoethmoidal and septopresphenoidal junctions with cell division at the
      synchondroses, and double-fluorochrome labeling was used to measure
      mineralization rate. The results showed that the septoethmoidal and
      septopresphenoidal junctions develop the characteristic morphology of growth
      plates postnatally, and that the pattern of cell division is similar to that of
      synchondroses. Mineralization at these junctions occurred at rates that were not
      statistically different from those of the synchondroses. However, the
      cartilaginous septum increased in length much more rapidly than could be
      explained by caudal growth, implying that interstitial expansion is the more
      important contributor to septal growth.

PMID- 17031812
TI  - Distinctive localization of N- and E-cadherins in rat anterior pituitary gland.
AB  - In the rat anterior pituitary gland, folliculo-stellate cells aggregate
      preferably to form pseudofollicles, and each type of hormone-producing cell shows
      adhesive affinity with particular types of heterologous hormone-producing cells.
      Distribution of cadherin types in the rat anterior pituitary was examined
      immunohistochemically to clarify the unique cell arrangements caused by
      homologous and heterologous affinities among cells. N- and E-cadherins were
      detected continuously along cell membranes, while P-cadherin was not. N- and E
      cadherins showed distinct isolation in localization, with N-cadherins localized
      in hormone-producing cells of distal and intermediate lobes in various amounts,
      and E-cadherins limited to folliculo-stellate cells and marginal layer cells
      facing the residual lumen of Rathke's pouch. A similar distribution of cadherins
      was observed in cell clusters of primary cultured anterior pituitary cells. These
      findings suggest that differential expression of cell adhesion molecules may be
      partially responsible for localization of hormone-producing cells and folliculo
      stellate cells.

PMID- 17031813
TI  - In vivo imaging of prostate cancer involving bone in a mouse model.
AB  - BACKGROUND: We compared the abilities of clinically relevant imaging modalities
      to quantify prostate cancer involving bone in a mouse model. Such non-invasive
      methods are needed pre-clinically to understand tumor biology and to evaluate
      therapy. METHODS: Human prostate cancer cells (MDA PCa 2b) or vehicle were
      injected into the right or left femur of SCID mice (n = 8). Radiography, computed
      tomography, and magnetic resonance imaging were performed 5 and 8 weeks later (n
      = 7). Bone scintigraphy (n = 6) was also performed at week 8. Imaging findings
      were compared with histology and correlated with contemporaneous serum prostate
      specific antigen levels. RESULTS: Among the modalities evaluated, only MR imaging
      delineated prostate tumors involving bone. Tumor volume assessed by MR imaging
      correlated with PSA levels (R(2) = 0.87, P < 0.001). MR imaging of tumors
      corresponded with histology. Imaging of mineralized bone by CT corresponded with
      histology. CONCLUSION: In a mouse model, prostate tumors involving bone can be
      quantified using MR imaging.

PMID- 17031814
TI  - Effects of obesity and height on prostate-specific antigen (PSA) and percentage
      of free PSA levels among African-American and Caucasian men.
AB  - BACKGROUND: Prior studies suggest that obese men have lower prostate-specific
      antigen (PSA) levels than leaner men. Caucasian (CA) men also may have lower PSA
      levels than African-American (AA) men, but the relevance of body size to racial
      disparities in PSA levels is unclear. The association between body mass index
      (BMI) and height on PSA and percentage of free PSA (%fPSA) was investigated
      within AA and CA men without a prior prostate cancer diagnosis. METHODS: AA (n =
      150) and CA (n = 149) men of similar socioeconomic status completed an extensive
      in-person interview and donated blood. PSA and %fPSA levels were compared across
      race, BMI, and height categories after adjusting for age and other factors.
      RESULTS: PSA levels decreased with increasing BMI (PSA = .72, .69, .67, .59 ng/mL
      for BMI 18.5 to <25, 25 to <30, 30 to <35, and > or =35, respectively; P(trend) =
      .18), and trends were significant among men less than age 60 years (PSA = .81,
      .76, .66, .59, respectively; P(trend) = .02). fPSA also significantly decreased
      with BMI among men <60 years (P(trend) = .04). In contrast, %fPSA was not
      associated with BMI. However, %fPSA increased 27% across height categories
      (P(trend) = .02). PSA levels were significantly lower among CA men (PSA(AA) =
      0.87, PSA(CA) = 0.63 ng/mL; P < .01), whereas %fPSA levels did not differ by
      race. Also, associations between body size and PSA or %fPSA did not significantly
      differ by race, and adjustment for BMI and height had no effect on the racial
      disparity in PSA (PSA(AA) = 0.87, PSA(CA) = 0.63 ng/mL; P < .01). CONCLUSIONS:
      The data suggest that race, BMI, and height are independently associated with PSA
      and %fPSA levels.

PMID- 17031816
TI  - Whole-body magnetization transfer contrast imaging.
AB  - PURPOSE: To demonstrate the feasibility of whole-body magnetization transfer (MT)
      contrast imaging. MATERIALS AND METHODS: Whole-body MT imaging was performed on
      eight healthy volunteers and five patients (mean age=40.5+/-17.8 years) with
      diagnoses of dermatomyositis (N=1), B-symptoms with suspicion of paraneoplastic
      disease (N=1), metastatic malignant melanoma (N=1), and multiple sclerosis (MS)
      (N=2). Measurements were carried out on a 1.5-Tesla whole-body MR scanner capable
      of parallel signal reception. A three-dimensional (3D) gradient-echo sequence
      (TR=17 msec, TE=4.8 msec, flip angle=10 degrees) was applied in combination with
      a Gaussian off-resonance MT preparation pulse acting at an off-resonance of 1.500
      Hz with a 500 degrees effective flip angle. Whole-body images were constructed
      from five different body regions. RESULTS: In all subjects, whole-body MT
      contrast images were obtained within less than 20 minutes of measuring time. The
      images showed sufficient diagnostic image quality to assess the patients'
      pathologies. The MT ratios (MTRs, in percent units) for the volunteers were as
      follows: white matter (WM) 51.1+/-1.0, gray matter (GM) 42.2+/-1.3, skeletal
      muscle (mean value of four muscle groups) 50.3+/-2.1, liver 39.4+/-3.2, spleen
      31.8+/-2.6, renal cortex 30.4+/-1.9, and renal medulla 25.6+/-1.3. The MTRs for
      the pathologies were as follows: skeletal muscle in dermatomyositis approximately
      30, metastases in malignant melanoma 30.7-36.0, uterus myoma 49.3, and MS lesions
      30-40. CONCLUSION: Our preliminary data indicate that MT contrast in whole-body
      MRI is feasible, and may be useful for rapid whole-body assessment of diseases
      that exhibit high contrast in MT imaging, such as MS and muscular disorders.

PMID- 17031815
TI  - Genome-wide linkage of 77 families from the African American Hereditary Prostate
      Cancer study (AAHPC).
AB  - BACKGROUND: The African American Hereditary Prostate Cancer (AAHPC) Study was
      designed to recruit families with early-onset disease fulfilling criteria of
      >or=4 affected. METHODS: We present a approximately 10 cM genome-wide linkage
      (GWL) analysis on 77 families including 254 affected and 274 unaffected
      genotyped. RESULTS: Linkage analysis revealed three chromosomal regions with
      GENEHUNTER multipoint HLOD scores >or=1.3 for all 77 families at 11q22, 17p11,
      and Xq21. One family yielded genome-wide significant evidence of linkage (LOD =
      3.5) to the 17p11 region with seven other families >or=2.3 in this region. Twenty
      nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62
      (alpha = 0.33) at the Xq21 locus. Two novel peaks >or=0.91 for the 16 families
      with '>6 affected' occurred at 2p21 and 22q12. CONCLUSIONS: These chromosomal
      regions in the genome warrant further follow-up based on the hypothesis of
      multiple susceptibility genes with modest effects, or several major genes
      segregating in small subsets of families.

PMID- 17031817
TI  - Detection of hepatic metastases using ferucarbotran-enhanced MR imaging:
      feasibility and diagnostic accuracy of three-dimensional sensitivity-encoding
      water-excitation multishot echo-planar sequence (3D-SWEEP).
AB  - PURPOSE: To evaluate the diagnostic accuracy of a ferucarbotran-enhanced three
      dimensional sensitivity-encoding water-excitation multishot echo-planar sequence
      (3D-SWEEP) for detecting hepatic metastases compared to a T2*-weighted fast field
      echo (FFE) sequence. MATERIALS AND METHODS: Twenty-five consecutive patients with
      hepatic metastases underwent ferucarbotran-enhanced MRI on a 1.5-T unit before
      hepatic resections. Eighty-two foci of metastases were confirmed by
      histopathology or intraoperative ultrasonography (US). Signal-intensity decay
      (SID), tumor-to-liver contrast (TLC), and image quality were compared between T2*
      weighted FFE and 3D-SWEEP. Three independent observers reviewed three imaging
      sets: set 1, without 3D-SWEEP or T2*-weighted FFE; set 2, with T2*-weighted FFE;
      and set 3, with 3D-SWEEP. The mean values of areas under alternative free
      response receiver operating characteristic curves (Az) and sensitivities were
      compared among the three sets. RESULTS: SID and TLC were significantly greater
      for 3D-SWEEP than T2*-weighted FFE, although 3D-SWEEP had poorer image quality.
      The mean Az and sensitivity were significantly greater for set 3 compared to set
      1 for detecting overall lesions, and compared to sets 1 and 2 for detecting
      lesions of 1-2 cm in diameter. CONCLUSION: Despite relatively prominent
      artifacts, ferucarbotran-enhanced 3D-SWEEP was more sensitive and accurate than
      T2*-weighted FFE for detecting hepatic metastases.

PMID- 17031818
TI  - Model-based registration for dynamic cardiac perfusion MRI.
AB  - PURPOSE: To assess the accuracy of a model-based approach for registration of
      myocardial dynamic contrast-enhanced (DCE)-MRI corrupted by respiratory motion.
      MATERIALS AND METHODS: Ten patients were scanned for myocardial perfusion on 3T
      or 1.5T scanners, and short- and long-axis slices were acquired. Interframe
      registration was done using an iterative model-based method in conjunction with a
      mean square difference metric. The method was tested by comparing the absolute
      motion before and after registration, as determined from manually registered
      images. Regional flow indices of myocardium calculated from the manually
      registered data were compared with those obtained with the model-based
      registration technique. RESULTS: The mean absolute motion of the heart for the
      short-axis data sets over all the time frames decreased from 5.3+/-5.2 mm (3.3+/
      3.1 pixels) to 0.8+/-1.3 mm (0.5+/-0.7 pixels) in the vertical direction, and
      from 3.0+/-3.7 mm (1.7+/-2.1 pixels) to 0.9+/-1.2 mm (0.5+/-0.7 pixels) in the
      horizontal direction. A mean absolute improvement of 77% over all the data sets
      was observed in the estimation of the regional perfusion flow indices of the
      tissue as compared to those obtained from manual registration. Similar results
      were obtained with two-chamber-view long-axis data sets. CONCLUSION: The model
      based registration method for DCE cardiac data is comparable to manual
      registration and offers a unique registration method that reduces errors in the
      quantification of myocardial perfusion parameters as compared to those obtained
      from manual registration.

PMID- 17031819
TI  - Processing, properties, and in vitro bioactivity of polysulfone-bioactive glass
      composites.
AB  - The mismatch between the mechanical properties of bioceramics and natural tissue
      has restricted in several cases a wider application of ceramics in medical and
      dental fields. To overcome this problem, polymer matrix composites can be
      designed to combine bioactive properties of some bioceramics with the superior
      mechanical properties of some engineering plastics. In this work, polymer
      particulate composites composed of a high mechanical-property polymer and
      bioactive glass particles were produced and both the in vitro bioactivity and
      properties of the system were investigated. Composites with different volume
      fraction and particle size were prepared. In vitro tests showed that hydroxy
      carbonate-apatite can be deposited on the surface of a composite as early as 20 h
      in a simulated body fluid. Ionic evolution from a composite with 40% volume
      fraction of particles was demonstrated to be similar to bulk bioactive glasses.
      The mechanical properties of some of the obtained composites had values
      comparable with the ones reported for bone. Moreover, a physical model based on
      dynamical mechanical tests showed evidences that the interface of the composite
      was aiding in the stress transfer process.

PMID- 17031820
TI  - Increased osteoblast adhesion on nanograined Ti modified with KRSR.
AB  - Peptide sequences such as lysine-arginine-serine-arginine (KRSR) selectively bind
      transmembrane proteoglycans (e.g. heparin sulfate) of osteoblasts (bone-forming
      cells) and are, therefore, actively being investigated for orthopedic
      applications. Further, nanophase materials (or materials with grain or particle
      sizes less than 100 nm) are promising new materials that promote new bone growth
      more than compared to conventional (that is, micron grain or particle size)
      materials. To combine the above two promising approaches for improving orthopedic
      implants, the objective of this in vitro study was to functionalize titanium (Ti)
      surfaces (both nanophase and conventional) with KRSR peptides and study their
      osteoblast cell adhesive properties. Materials were characterized by X-ray
      photoelectron spectroscopy, scanning electron microscopy, and atomic force
      microscopy. Results of this in vitro study provided evidence of increased
      osteoblast adhesion on nanophase compared to conventional Ti whether
      functionalized with KRSR or not. Results further showed that the immobilization
      of KRSR onto Ti (both nanophase and conventional) increased osteoblast adhesion
      compared to respective nonfunctionalized Ti and those functionalized with the
      negative control peptide KSRR. Most importantly, osteoblast adhesion on
      nonfunctionalized nanophase Ti increased compared to conventional Ti
      functionalized with KRSR. Further, select initial osteoblast adhesion was
      observed to occur at particle boundaries for any type of nanophase and
      conventional Ti formulated in this study. In summary, results provided evidence
      that not only should nonfunctionalized nanophase Ti be further studied for
      improved orthopedic applications but so should nanophase Ti functionalized with
      KRSR.

PMID- 17031821
TI  - Enhancement of in vitro osteogenesis on titanium by chemically produced
      nanotopography.
AB  - The surface characteristics of biomaterials can influence protein adsorption,
      cellular functions, and ultimately tissue formation. Controlled chemical
      oxidation of titanium-based surfaces with a mixture of H(2)SO(4)/H(2)O(2) creates
      a nanopatterned surface that has been shown to affect early osteogenic events.
      The objective of this study was to evaluate the effect over time of this
      nanopattern on various key parameters of osteogenesis, and determine whether
      these effects ultimately translate into more mineralized matrix production.
      Osteogenic cells were obtained by enzymatic digestion of newborn rat calvaria and
      grown on treated and untreated titanium discs for periods of up to 14 days.
      Alkaline phosphatase activity peaked earlier and cell number was higher as of day
      7 on the nanopatterned discs. Immunofluorescence showed that the treated surface
      favored early bone sialoprotein and osteopontin secretion, and fibronectin
      accumulation. Alizarin red staining revealed that, at days 10 and 14, there were
      significantly more mineralized nodules on treated than on untreated discs. These
      results demonstrate that simple chemical treatment of titanium with
      H(2)SO(4)/H(2)O(2) accelerates the in vitro osteogenic potential of calvaria
      derived cells. They also suggest that this treatment may represent an
      advantageous approach for producing "intelligent surfaces" that stimulate bone
      formation and enhance bone-implant contact.

PMID- 17031822
TI  - Antibacterial nanosized silver substituted hydroxyapatite: synthesis and
      characterization.
AB  - The silver (0.5-3 at %) substituted nanosize hydroxyapatites (AgHAs) were
      synthesized by microwave processing. The X-ray diffraction (XRD) peaks are very
      broad, indicating that the AgHAs were of nanosize (30 nm). Transmission electron
      microscopy analysis shows needle-like morphology of AgHA, having length 60-70 nm
      and width 15-20 nm. The AgHA phase was stable up to 700 degrees C without any
      secondary phases. The antibacterial effect of AgHA against Escherichia coli and
      Staphylococcus aureus was observed by spread plate method, even for low
      concentration of silver ions (0.5%) with 1 x 10(5) cells/mL of respective
      bacterial culture, after a 48 h incubation period. However, some colonies of E.
      coli were seen with a high dose of 1 x 10(8) cells/mL after 24 h. The zone of
      inhibition by disc diffusion test method was found to vary with the amount of
      silver in the sintered AgHA pellets, for both the bacteria, after 24 h of
      inoculation. Osteoblast cell attachment in varying density was noticed on AgHA
      samples with 0.5, 1.0, and 1.5% silver substitution. However, osteoblast
      spreading was significantly greater on 0.5% AgHA compared to 1.0 or 1.5%
      substituted AgHA samples. Thus, the low amount of AgHA has a potential of
      minimizing the risk of bacterial contamination, without compromising the
      bioactivity, and is expected to display greater biological efficacy in terms of
      osseointegration.

PMID- 17031823
TI  - Effect of the solution flow rate on the in vitro bioactivity of 2.5CaO x 2SiO(2)
      glass.
AB  - A comparative study of in vitro bioactivity of 2.5CaO x 2SiO(2) glass has been
      carried out by soaking it in a simulated body fluid, with continuously and
      periodic exchange of this solution (dynamic and differential protocols). Dynamic
      assays were carried out at different solution flow rates, 3 mL/h, 6 mL/h, 12
      mL/h, to study the influence of flow rate on glass reactivity. Glass surface was
      studied by Fourier transform infrared spectroscopy, scanning electron microscopy,
      and energy dispersive spectroscopy so as to compare the behavior in the two
      procedures, revealing that in both cases an apatite layer is formed on the glass
      surface, although there are differences on deposition rate and morphology, which
      are also influenced by the solution flow rate.

PMID- 17031824
TI  - Macrophage behavior on multilayered DNA-coatings in vitro.
AB  - A pivotal factor to consider in the development of biomaterials and biomaterial
      coatings is the inflammatory response to these materials. The insertion of
      implants is followed by protein adsorption and subsequent interactions with
      cellular components of the biological surroundings, in which macrophages play a
      dominant role through the production of a myriad of signaling molecules. In view
      of this, the aims of the present study were to evaluate (i) gross protein
      adsorption to, and (ii) in vitro behavior of macrophages on novel biomaterial
      coatings, composed of poly-D-lysine (PDL) or poly(allylamine hydrochloride) (PAH)
      and DNA, and to compare these coatings with negative (noncoated glass) and
      positive controls (noncoated glass + LPS-stimulation). The results demonstrate
      that multilayered DNA-coatings do not affect gross protein adsorption compared to
      noncoated controls. Cell culture experiments showed that the attachment to, and
      viability and morphology of two types of macrophages cultured on multilayered DNA
      coatings is comparable to noncoated controls. Still, macrophages repeatedly
      showed decreased secretion levels of the proinflammatory cytokine TNF-alpha on
      multilayered DNA-coatings, whereas no differences were observed in the secretion
      of IL-1beta, IL-10, and TGF-beta1. Appropriate animal studies are required to
      elucidate if these in vitro indications have clinical effects on the inflammatory
      and wound healing processes around implants.

PMID- 17031825
TI  - Detection of HCV antigens in liver graft: relevance to the management of
      recurrent post-liver transplant hepatitis C.
AB  - The aim of this study was to evaluate how the immunohistochemical detection of
      liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic
      diagnosis and influence the clinical management of post-liver transplantation
      (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients
      with post-LT liver disease were studied. Histologic coding was: hepatitis (126),
      rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or
      other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on
      frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early
      in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and
      74% of cases after more than 180 days. Overall, HCV-Ag were detected more
      frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a
      higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a
      high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical
      diagnosis of recurrent hepatitis (RHC) was made despite inconclusive
      histopathologic diagnosis. Multivariate analysis identified the percentage of HCV
      Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P
      = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive
      hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001)
      in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV
      reinfection occurs early post-LT, reaching its peak within 6 months.
      Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of
      hepatitis when the histologic features are not conclusive. A high number of
      infected cells, independently from the genotype, represents a negative predictive
      factor of response to antiviral treatment.

PMID- 17031826
TI  - Recurrence of autoimmune liver disease after liver transplantation: a systematic
      review.
AB  - Recurrence of autoimmune liver disease in allografts has long been a topic of
      debate. We conducted a systematic review of the literature to examine the
      reported incidence of recurrence after liver transplantation of primary biliary
      cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis
      (AIH). The MEDLINE, EMBASE, and Cochrane electronic databases were used to
      identify articles. The inclusion criteria used were articles on patients with at
      least 90 days of posttransplantation follow-up, histologic criteria for diagnosis
      of PBC and AIH recurrence, radiologic or histologic criteria or both for
      diagnosis of PSC recurrence, and exclusion of other causes of liver disease
      causing similar histologic findings. Incidence in individual studies was combined
      to calculate the overall recurrence. Risk factors were analyzed whenever crude
      data were available. Funnel plots were used to assess publication bias. Out of 90
      articles identified, 43 met criteria for systematic review (PBC, 16; PSC, 14;
      AIH, 13). The calculated weighted recurrence rate was 18% for PBC, 11% for PSC,
      and 22% for AIH. No difference was found in PBC and AIH recurrence by type of
      primary immunosuppression. There were not enough data to assess this issue in PSC
      studies. There was evidence of publication bias among PSC and AIH studies but not
      among PBC studies. In conclusion, recurrence of autoimmune liver disease after
      liver transplantation appears to be a real concern. As these patients are
      followed long-term, recurrence of disease may become the primary cause of
      morbidity.

PMID- 17031827
TI  - Transhepatic lactate gradient in relation to liver ischemia/reperfusion injury
      during major hepatectomies.
AB  - Hepatectomies performed under selective hepatic vascular exclusion are associated
      with a series of events culminating in ischemia/reperfusion injury, a state that
      shares common characteristics with situations known to result in global or
      regional hyperlactatemia. Accordingly, we sought to determine whether lactate is
      released by the liver during hepatic resections performed under blood flow
      deprivation and what relation this has to a possible systemic hyperlactatemic
      state. After ethical approval, 14 consecutive patients with resectable liver
      tumors subjected to hepatectomy under inflow and outflow occlusion of the liver
      were studied. Lactate concentrations were assessed in simultaneously drawn
      arterial, portal venous, and hepatic venous blood before liver dissection and 50
      minutes postreperfusion. Moreover, the transhepatic lactate gradient (hepatic
      vein - portal vein) was calculated to see if there was net production or
      consumption of lactate. Before hepatic dissection, the transhepatic lactate
      gradient was negative, suggesting consumption by the liver. Fifty minutes after
      reperfusion, this gradient became significantly positive, demonstrating release
      of lactate by the liver (0.12 +/- 0.31 vs. -0.38 +/- 0.30 mmol/L, P < 0.05). The
      magnitude of lactate release correlated with systemic arterial lactate levels at
      the same time point (r(2) = 0.63, P < 0.001). A weaker but significant
      correlation was demonstrated between the transhepatic lactate gradient
      postreperfusion and systemic arterial lactate levels 24 hours postoperatively
      (r(2) = 0.41, P = 0.013). A strong correlation between the transhepatic lactate
      gradient postreperfusion and peak postoperative aspartate aminotransferase values
      was also demonstrated (r(2) = 0.73, P < 0.001). The liver becomes a net producer
      of lactate in hepatectomies performed under blood flow deprivation. This lactate
      release can explain some of the systemic hyperlactatemia seen in this context and
      relates to the extent of ischemia/reperfusion injury.

PMID- 17031828
TI  - Impact of adult-to-adult living donor liver transplantation on access to
      transplantation and patients' survival: an 8-year single-center experience.
AB  - While the number of candidates for liver transplantation has increased in the
      recent years, the pool of cadaveric donor organs has remained constant and the
      waiting time progressively increases. These facts led us to start a program of
      adult-to-adult living-donor liver transplantation in 1998. The aim of this study
      was to compare the outcome of all patients put on the waiting list since 1998.
      Between January 1, 1998, and January 1, 2005, 505 patients were put on the
      waiting list in our center, and living donor liver transplantation was considered
      in 57 cases (11.3%). At the time of evaluation (April 1, 2006), liver
      transplantation was performed in 377 patients (46 living donor liver
      transplantations), and 89 patients died on waiting list. On an intention-to-treat
      basis, the 1-year survival rate from the time of listing was 87.5% in the "living
      donor" group vs. 76.2% in the "cadaveric donor" group (P < 0.05), whereas the 1
      year survival after liver transplantation was similar (92.3% vs. 86.9%). Our
      living donor liver transplantation program was able to improve the access to
      liver transplantation by reducing waiting time and the number of deaths on
      waiting list, despite the fact that these patients were more critically ill
      (liver failure and/or liver cancer).

PMID- 17031829
TI  - Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent
      extended cold storage in University of Wisconsin solution in an extracorporeal
      rat liver perfusion and rat liver transplantation model.
AB  - Adequate flushing for liver donation requires large fluid volumes delivered at a
      high flow. This can be achieved more effectively with crystalloid solutions than
      with colloid-based solutions. This study examined the combination of initial
      histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent
      storage in University of Wisconsin solution (UW) to that of the single use of
      each solution. Livers from inbred Wistar rats were procured using aortic
      perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes
      using either solution. In a third group, after perfusion with HTK, organs were
      reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed
      after 24 hours of cold storage in the subsequent solution, as well as
      allotransplantation after 18 and 24 hours of cold storage. In extracorporeal
      perfusion, the HTK flush followed by UW storage was superior compared to the
      single use of either UW or HTK solution, as measured by portal venous pressure,
      bile flow, liver enzymes released into the effluent perfusate, glycerol leakage,
      and histological examinations. These data were consistent with the
      transplantation study. Histological damage and enzyme release after 5-day
      survival were lowest in the HTK flush and subsequent UW storage groups following
      18 hours of cold storage; likewise, the 5-day survival was superior following 24
      hours of cold storage. In conclusion, the combined use of HTK solution for
      initial graft rinse and subsequent storage in UW solution resulted in a
      cumulative protection. Choosing low-viscosity HTK solution for the initial organ
      flush may represent a feasible improvement in liver preservation, which also
      further reduces the required amount of UW solution.

PMID- 17031830
TI  - Identification of hepatitis B virus-specific lymphocytes in human liver grafts
      from HBV-immune donors.
AB  - Both animal and human studies have demonstrated the adoptive transfer of immunity
      against hepatitis B virus (HBV) through liver transplantation that may be
      attributed to the presence of HBV-specific immunocompetent cells of donor origin
      in liver grafts. In this study, we characterized the resident lymphocytes in 41
      human liver grafts by immunohistochemical staining and flow cytometry and
      directly identified the intragraft HBV-specific lymphocytes in relation to the
      donor's and subsequent recipient's immunity using enzyme-linked immunospot assay.
      A significant number of HBV-specific T and B cells were detectable in 59.4%
      (19/32) and 28.1% (9/32), respectively, of liver grafts from HBV-immune donors.
      The presence of various HBV-specific lymphocytes was closely associated with each
      other and with a higher serum titer of antibody against hepatitis B surface
      antigen (anti-HBs) in donors (P < 0.05). After liver transplantation, 17 of 35
      (48.6%) patients with chronic HBV infection showed a spontaneous anti-HBs
      production, which was significantly associated with a higher number of donor
      derived T lymphocytes specific for hepatitis B surface antigen (P = 0.043). In
      conclusion, the presence of considerable numbers of donor-derived HBV-specific
      immunocompetent cells in grafts may account for the adoptive transfer of HBV
      immunity through liver transplantation.

PMID- 17031831
TI  - Estimation of glomerular filtration rates after orthotopic liver transplantation:
      Evaluation of cystatin C-based equations.
AB  - Early detection of renal dysfunction in patients after orthotopic liver
      transplantation is important. Creatinine-based equations to estimate glomerular
      filtration rate (GFR) were found to be less accurate in liver transplant
      recipients than in their original populations. Since cystatin C (CysC) is
      independent from muscle mass and hepatic biosynthesis, we evaluated the
      diagnostic accuracy of 3 CysC-based equations (Larson, Hoek, and Filler formulae)
      that are based on the same CysC method as that of our center in comparison to the
      abbreviated creatinine-based modification of diet in renal disease (MDRD) formula
      in 59 liver transplant recipients. "True GFR" was measured by 99mTc-diethylene
      triamine pentaacetic acid ((99m)Tc-DTPA) clearance. Neither correlation with the
      GFR (correlation coefficients: 0.594-0.640) nor precision (root mean square
      error: 15.7-18.17 mL/min/1.73 m(2)) differed significantly between the tested
      formulae. The biases of the Hoek and Larsson formulae were significantly smaller
      than those of the MDRD and Filler equations (-0.1 and -2.3 vs. 10.1 and 7.9
      mL/min/1.73 m(2), respectively; P </= 0.0023). Mean estimates of MDRD (61.9 +/-
      21.4 mL/min/1.73 m(2)) and Filler (61.2 +/- 22.1 mL/min/1.73 m(2)) differed
      significantly from the measured GFR (52.3 +/- 17.5 mL/min/1.73 m(2); P < 0.005),
      whereas Larsson and Hoek did not (49.5 +/- 20.2 and 51.4 +/- 17.9 mL/min/1.73
      m(2), respectively). Accuracy within 30% and 50% of the true GFR was best for the
      Hoek (76.3% and 93.2%) formula, albeit not significantly different from MDRD
      (64.4% and 83.1%). Taken together, these data show the best overall performance
      for GFR estimates derived from the Hoek equation with respect to bias, precision,
      and accuracy.

PMID- 17031832
TI  - Correlation between dynamic susceptibility contrast perfusion MRI and methionine
      metabolism in brain gliomas: preliminary results.
AB  - PURPOSE: To evaluate in brain gliomas the relationship between tumor vascularity
      measured by MR-based maximum regional cerebral blood volume (rCBV) and tumor
      amino-acid metabolism based on maximum carbon-11 methionine (MET) uptake on
      positron emission tomography (PET). MATERIALS AND METHODS: Eighteen patients with
      histologically proven primary brain gliomas were included in the study. In
      addition to conventional MR sequences, dynamic MR images, including a first-pass
      gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence and a PET
      study using MET, were acquired. Eleven patients had low-grade gliomas, and seven
      had high-grade gliomas. rCBV ratios and MET uptake ratios normalized to the
      contralateral white matter (WM) corresponding values were measured in each tumor.
      Both maximum rCBV ratios and maximum MET uptake ratios were correlated to
      histopathology. The maximum rCBV ratios were correlated to the maximum MET uptake
      ratios. RESULTS: Both the maximum rCBV ratios and maximum MET uptake ratios of
      high-grade gliomas were significantly higher than those of low-grade gliomas
      (P<0.05). There was a significant positive correlation between maximum rCBV
      ratios and maximum MET uptake ratios (Spearman: r=0.89, P<0.00001). CONCLUSION:
      The maximum rCBV ratio and maximum MET uptake ratio are significantly correlated
      in gliomas, reflecting a close link between amino acid uptake and vascularity in
      these tumors.

PMID- 17031833
TI  - Fast magnetization-driven preparation for imaging of contrast-enhanced coronary
      arteries during intra-arterial injection of contrast agent.
AB  - PURPOSE: To implement a short-duration magnetization preparation sequence, which
      consists of a saturation followed by multiple inversion pulses, for imaging of
      short-T1 species and suppression of long-T1 species. MATERIALS AND METHODS:
      Computer optimizations were performed to derive preparation schemes that 1)
      suppress long-T1 background species with T1>or=250 msec, 2) maximize the MZ of
      contrast-enhanced (CE) structures with T1<or=50 msec, and 3) have a preparation
      duration in the range of 200 msec. The optimized sequences were tested on a
      phantom and a pig model instrumented with an intracoronary catheter for infusion
      of contrast media. RESULTS: Computer simulations generated preparation schemes
      with durations of 165-225 msec depending on the number of preparation pulses
      used, which generated saturation of over 98% for T1>250 msec, and about a 30%
      reduction for 20 msec<T1<50 msec. The phantom studies validated the performance
      of the optimized sequences. Coronary artery angiograms (380 msec for preparation
      and image acquisition) demonstrated signal-to-noise ratios (SNRs) in the range of
      13-15.5 and contrast-to-noise ratios (CNRs) in the range of 6.3-7.1 in the CE
      coronary vessels. CONCLUSION: This work demonstrates that fast magnetization
      driven preparation schemes can be implemented for fast imaging of CE coronary
      vessels with efficient saturation of background species.

PMID- 17031834
TI  - Improved myocardial tagging contrast in cine balanced SSFP images.
AB  - PURPOSE: To improve the tag persistence throughout the whole cardiac cycle by
      providing a constant tag-contrast throughout all the cardiac phases when using
      balanced steady-state free precession (bSSFP) imaging. MATERIALS AND METHODS: The
      flip angles of the imaging radiofrequency pulses were optimized to compensate for
      the tagging contrast-to-noise ratio (Tag-CNR) fading at later cardiac phases in
      bSSFP imaging. Complementary spatial modulation of magnetization (CSPAMM) tagging
      was implemented to improve the Tag-CNR. Numerical simulations were performed to
      examine the behavior of the Tag-CNR with the proposed method, and to compare the
      resulting Tag-CNR with that obtained from the more commonly used spoiled gradient
      echo (SPGR) imaging. A gel phantom, as well as five healthy human volunteers,
      were scanned on a 1.5T scanner using bSSFP imaging with and without the proposed
      technique. The phantom was also scanned with SPGR imaging. RESULTS: With the
      proposed technique, the Tag-CNR remained almost constant during the whole cardiac
      cycle. Using bSSFP imaging, the Tag-CNR was about double that of SPGR.
      CONCLUSION: The tag persistence was significantly improved when the proposed
      method was applied, with better Tag-CNR during the diastolic cardiac phase. The
      improved Tag-CNR will support automated tagging analysis and quantification
      methods.

PMID- 17031835
TI  - Displacement of the facial nerve course by vestibular schwannoma: preoperative
      visualization using diffusion tensor tractography.
AB  - PURPOSE: To preoperatively visualize the course of the facial nerve, which is
      displaced by vestibular schwannoma, using diffusion tensor (DT) tractography, and
      to evaluate the agreement with surgical findings. MATERIALS AND METHODS: The
      subjects were eight patients with vestibular schwannoma who had undergone removal
      surgery. DT MR images were obtained and tracts that were considered to represent
      the facial nerve were constructed. We assessed the success rate for tract
      construction and evaluated the agreement between tractography findings and
      surgery. RESULTS: We obtained a tract that connected the internal auditory meatus
      and brainstem, and was considered to represent the facial nerve in seven of eight
      cases. The course of the constructed tract agreed with surgical findings in five
      of these seven cases. One exception was a case in which the tumor was too large
      to enable intraoperative observation of the facial nerve; however, the facial
      nerve appeared to be displaced anteriorly at intracapsular resection, in
      agreement with tractography. In the other case, the schwannoma was mostly cystic.
      CONCLUSION: Tractographs constructed using MR tensor images enabled us to
      identify tracts considered to represent facial nerves. We consider DT
      tractography to be a useful tool for preoperatively predicting facial nerve
      displacement in vestibular schwannoma.

PMID- 17031836
TI  - Strengths and weaknesses of dark-lumen MR colonography: clinical relevance of
      polyps smaller than 5 mm in diameter at the moment of their detection.
AB  - PURPOSE: To assess the clinical relevance of dark-lumen MR colonography (MRC) for
      the detection of colorectal lesions using conventional colonoscopy (CC) and
      histopathologic examinations as reference standard. MATERIALS AND METHODS: A
      total of 72 patients underwent MRC and CC. MRC was performed using a contrast
      enhanced high spatial resolution T1 weighted 3D volumetric interpolated
      breathhold examination (VIBE)-sequence. All removed colorectal lesions were
      evaluated by an experienced pathologist. RESULTS: CC confirmed 65 polyps less
      than 5 mm in diameter. Non of those lesions could be detected using MRC. Just two
      (4%) of the 49 removed lesions smaller than 5 mm showed signs of dysplasia.
      Additionally, CC confirmed 25 polyps between 6-15 mm in diameter (MRC 22). All
      those 25 lesions were removed in CC. Only four (16%) of those polyps showed signs
      of dysplasia and malignancy (11, 13, 13 and 15 mm). CONCLUSION: Dark-lumen MRC
      failed to detect all polyps smaller than 5 mm in diameter which are generally not
      clinically relevant at the moment of their detection and thus can be kept under
      surveillance. However, MRC as a non-invasive imaging modality is a promising
      alternative to CC in the detection of clinically relevant polyps larger than 5 mm
      in diameter.

PMID- 17031837
TI  - Quantification of distal antral contractile motility in healthy human stomach
      with magnetic resonance imaging.
AB  - PURPOSE: To quantify healthy postprandial: 1) propagation, periodicity, geometry,
      and percentage occlusion by distal antral contraction waves (ACWs); and 2)
      changes in ACW activity in relationship to gastric emptying (GE). MATERIALS AND
      METHODS: Using 1.5-T MR scanner, nine healthy fasted volunteers were examined in
      the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal)
      with 500 microM Gd-DOTA. Total gastric (TGV) and meal volumes (MV) were assessed
      every five minutes for 90 minutes, in and interspersed with dynamic scan
      sequences (duration: 2.78 minutes) providing detailed images of distal ACWs.
      RESULTS: TGV increased by 738+/-38 mL after ingestion (t0), subsequently
      decreasing in parallel to GE. The mean GE rate and half-emptying time were 24+/-3
      mL/5 minutes and 71+/-6 minutes, respectively. Accompanying ACWs reached a
      periodicity of 23+/-2 seconds at t35 and propagated at an unvarying speed of
      0.27+/-0.01 cm/second. Their amplitude of 0.70+/-0.08 cm was constant, but the
      width decreased along the antral wall by 6+/-2%/cm (P=0.003). ACWs were
      nonocclusive (percentage occlusion 58.1+/-5.9%, t0 at the pylorus) with a
      reduction in occlusion away from the pylorus (P<0.001). No propagation and
      geometry characteristics of ACWs correlated with the changes of MV (mL/5 minutes;
      R2<0.05). CONCLUSION: Our results indicate that ACWs are not imperative for
      emptying of liquids. This study provides a detailed quantitative reference for
      MRI inquiries into pharmacologically- and pathologically-altered gastric
      motility.

PMID- 17031838
TI  - Contact force- and amplitude-controllable vibrating probe for somatosensory
      mapping of plantar afferences with fMRI.
AB  - PURPOSE: To study cerebral responses evoked from mechanoreceptors in the human
      foot sole using a computer-controlled vibrotactile stimulation system. MATERIALS
      AND METHODS: The stimulation system consisted of two stationary moving magnet
      actuators with indentors to gently contact and vibrate the foot sole during
      functional MRI (fMRI) experiments. To allow independent settings of contact force
      (0-20 N) and intensity of vibration (frequency range=20-100 Hz) the actuators
      were controlled by a digital servo loop. For fMRI experiments with complex
      stimulus protocols, both vibrating probes were further operated under supervisory
      control. RESULTS: The MR compatibility of this electromagnetic system was tested
      in a 1.5T scanner with an actively shielded magnet (Siemens Magnetom Sonata).
      Blood oxygenation level-dependent (BOLD) responses were detected in the
      contralateral left pre- and postcentral gyrus, bilaterally within the secondary
      somatosensory cortex, bilaterally within the supplementary motor cortex, and
      bilaterally within the anterior cingular gyrus. CONCLUSION: This stimulation
      device provides a new tool for identifying cerebral structures that convey
      sensory information from the foot region, which is of promising diagnostic value,
      particularly for assessing sensorimotor deficits resulting from brain lesions.

PMID- 17031839
TI  - T2* effects in the dual-sequence method for high-dose first-pass myocardial
      perfusion.
AB  - PURPOSE: To examine whether T2* effects reduce the accuracy of arterial input
      function (AIF) measurement by the dual-sequence method. MATERIALS AND METHODS:
      The dual-sequence method obtains a low-resolution AIF image and high-resolution
      myocardial images in each cycle, with suitable T1 weightings. It was modified to
      assess T2* effects in the low-resolution AIF image (4.8x4.8x10 mm voxels, TE=0.58
      msec) by minimizing T1 weighting in that sequence, while the myocardial sequence
      remained T1-weighted. In 10 patients who underwent perfusion MRI scans (0.5 M
      Magnevist, 0.1 mmol/kg, 15-ml flush, 7 mL/second right antecubital) the blood
      signal in the left ventricle (LV) was measured at the bolus peak and compared
      with the first cycle's fresh magnetization signal. RESULTS: The bolus peak
      measured 98%+/-4% (mean+/-SD, N=20) of the value before contrast agent arrival.
      CONCLUSION: T2* causes insignificant error in the dual-sequence method at the
      stated parameters.

PMID- 17031840
TI  - Involvement of p120 catenin in myopodial assembly and nerve-muscle synapse
      formation.
AB  - At developing neuromuscular junctions (NMJs), muscles initially contact motor
      axons by microprocesses, or myopodia, which are induced by nerves and nerve
      secreted agrin, but it is unclear how myopodia are assembled and how they
      influence synaptic differentiation at the NMJ. Here, we report that treatment of
      cultured muscle cells with agrin transiently depleted p120 catenin (p120ctn) from
      cadherin junctions in situ, and increased the tyrosine phosphorylation and
      decreased the cadherin-association of p120ctn in cell extracts. Whereas ectopic
      expression of wild-type p120ctn in muscle generated myopodia in the absence of
      agrin, expression of a specific dominant-negative mutant form of p120ctn, which
      blocks filopodial assembly in nonmuscle cells, suppressed nerve- and agrin
      induction of myopodia. Significantly, approaching neurites triggered reduced
      acetylcholine receptor (AChR) clustering along the edges of muscle cells
      expressing mutant p120ctn than of control cells, although the ability of the
      mutant cells to cluster AChRs was itself normal. Our results indicate a novel
      role of p120ctn in agrin-induced myopodial assembly and suggest that myopodia
      increase muscle-nerve contacts and muscle's access to neural agrin to promote NMJ
      formation.

PMID- 17031841
TI  - A fourth hominin skull from Dmanisi, Georgia.
AB  - Newly discovered Homo remains, stone artifacts, and animal fossils from Dmanisi,
      Republic of Georgia, provide a basis for better understanding patterns of hominin
      evolution and behavior in Eurasia ca. 1.77 million years ago. Here we describe a
      fourth skull that is nearly complete, lacking all but one of its teeth at the
      time of death. Both the maxillae and the mandible exhibit extensive bone loss due
      to resorption. This individual is similar to others from the site but supplies
      information about variation in brain size and craniofacial anatomy within the
      Dmanisi paleodeme. Although this assemblage presents numerous primitive
      characters, the Dmanisi skulls are best accommodated within the species H.
      erectus. On anatomical grounds, it is argued that the relatively small-brained
      and lightly built Dmanisi hominins may be ancestral to African and Far Eastern
      branches of H. erectus showing more derived morphology.

PMID- 17031842
TI  - Does static precede dynamic osteogenesis in endochondral ossification as occurs
      in intramembranous ossification?
AB  - Endochondral ossification takes place with calcified cartilage cores providing a
      rigid scaffold for new bone formation. Intramembranous ossification begins in
      connective tissue and new bone formed by a process of static ossification (SO)
      followed by dynamic ossification (DO) as previously described. The aim of the
      present study was to determine if the process of endochondral ossification is
      similar to that of intramembranous ossification with both a static and a dynamic
      phase of osteogenesis. Endochondral ossification centers of the tibiae and humeri
      of newborn and young growing rabbits were studied by light and transmission
      electron microscopy. The observations clearly showed that in endochondral
      ossification, the calcified trabeculae appeared to be lined first by osteoclasts.
      The osteoclasts were then replaced by flattened cells (likely cells of the
      reversal phase) and finally by irregularly arranged osteoblastic laminae, typical
      of DO. This cellular sequence did not include osteoblasts seen in the phase of
      SO. These findings clearly support our working hypothesis that SO only forms in
      soft tissues to provide a rigid framework for DO, and that DO requires a rigid
      mineralized surface. The presence of osteocytes in contact with the calcified
      cartilage also suggests the existence of stationary osteoblasts in endochondral
      ossification. Stationary osteoblasts did not appear to be a unique feature of SO.
      The presence of stationary osteoblasts may appear to provide the initial
      osteocytes during osteogenesis that may function as mechanosensors throughout the
      bone tissue. If this is the case, then bone would be capable of sensing
      mechanical strains from its inception.

PMID- 17031843
TI  - Effects of gamma radiation on beta-lactoglobulin: oligomerization and
      aggregation.
AB  - The conformational changes and aggregation process of beta-lactoglobulin (beta
      LG) subjected to gamma irradiation are presented. Beta-LG in solutions of
      different protein concentrations (3 and 10 mg/ml) and in solid state with
      different water activities (a(w)) (0.22; 0.53; 0.74) was irradiated using a
      Cobalt-60 radiation source at dose level of 1-50 kGy. Small-angle X-ray
      scattering (SAXS) was used to study the conformational changes of beta-LG due to
      the irradiation treatment. The irradiated protein was also examined by high
      performance size exclusion chromatography (HPSEC) and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing and reducing
      conditions and fluorescence. SAXS analysis showed that the structural
      conformation of irradiated beta-LG in solid state at different a(w) and dose
      level was essentially the same as the nonirradiated beta-LG. The scattering data
      also showed that the irradiation of beta-LG in solution promoted the formation of
      oligomers. Interestingly, from the data analysis and model building, it could be
      shown that the formed oligomers are linear molecules, built by linear
      combinations of beta-LG dimers (tetramers, hexamers, etc). The formation of
      oligomers was also evidenced by SDS-PAGE analysis and HPSEC chromatograms, in
      which products with higher molecular mass than that of the dimeric beta-LG were
      detected. Formation of intermolecular cross-linking between tyrosyl radicals are
      proposed to be at least partially responsible for this occurrence. From the
      results it could be shown that the samples irradiated in solution presented some
      conformational changes under gamma irradiation, resulting in well ordered
      oligomers and aggregates formed by cross-linking of beta-LG dimers subunits,
      while the samples irradiated in the solid state were not modified.

PMID- 17031844
TI  - Hydrocolloid carriers with filler inclusion for diltiazem hydrochloride release.
AB  - Hydrocolloid beads based on agarose, alginate (both 3%, w/w), or gellan (2%, w/w)
      were produced to study their potential as drug carriers. The beads included
      various fillers: talc, kaolin, calcium carbonate, potato, or corn starch (10%,
      w/w). After gelation, the carriers were subjected to either freeze- or vacuum
      drying. The dried carriers were spheroids. The diameters of freeze- and vacuum
      dried carriers ranged from 2.4 to 4.1 mm and 1.5 to 2.8 mm, respectively. The
      porosity values of the freeze-dried carriers were significantly higher than those
      of their vacuum-dried counterparts. Scanning electron microscopy (SEM) revealed
      that all dried carriers included internal voids that were partially occupied by
      the filler particles. Upon their introduction into simulated gastric fluid (3 h),
      followed by 6 h in intestinal fluid, all carriers were stable and underwent
      swelling. Release profiles of diltiazem hydrochloride from different carriers
      were obtained during immersion in dissolution medium. Filler inclusion (but not
      the type of filler) contributed to the stability of the carriers and prolonged
      the time of drug release (6.5-8.5 h) relative to the faster drug release from
      carriers that contained no filler (3.5 h). In summary, alginate, agar, and gellan
      beads with filler inclusion may be useful for slow drug release.

PMID- 17031845
TI  - Infrared microscopy for in situ measurement of protein secondary structure during
      freezing and freeze-drying.
AB  - A commercially available freeze-dry microscopy stage interfaced with an IR
      microscope is described as a method of in situ measurement of protein secondary
      structure in the liquid, frozen and freeze-dried states. Studies using solutions
      of model proteins demonstrated that spectra collected using the IR microscope
      have resolution and sensitivity that is comparable to techniques using a
      conventional infrared spectrometer. Additionally, spectra collected in triplicate
      on the microscope in the solution, frozen, and freeze-dried states and after
      reconstitution were shown to be reproducible. The limiting factor when collecting
      spectra on the infrared microscope appears to be the higher level of water vapor
      inherently present within the optical path of the microscope used in this study.
      Results demonstrate that the native secondary structure is perturbed in both the
      frozen and freeze-dried states, and bands characteristic of structural changes
      associated with freezing and drying stresses were observed in the Amide I region.
      Freeze-drying studies conducted in the presence of mannitol and sucrose
      demonstrated that perturbation to the native state secondary structure after
      freeze-drying was considerably reduced in the presence of these excipients.

PMID- 17031846
TI  - A calorimetric investigation of thermodynamic and molecular mobility
      contributions to the physical stability of two pharmaceutical glasses.
AB  - The purpose of this work was to investigate the contribution of thermodynamics
      and mobility to the physical stability of two pharmaceutical glasses with similar
      glass transition temperatures (Tg), by comparing configurational thermodynamic
      quantities and molecular relaxation time constants (tau) at temperatures below
      Tg. Ritonavir and nifedipine were chosen as model glasses because they show
      excellent and poor physical stability, respectively. Although ritonavir and
      nifedipine have similar Tg values (50 and 46 degrees C, respectively), amorphous
      ritonavir is quite stable while nifedipine has been reported to crystallize at
      temperatures as low as 40 degrees C below Tg. Modulated temperature differential
      scanning calorimetry (MTDSC) was used to characterize both crystalline phases and
      freshly prepared glasses. The glasses were then annealed at Tg-Ta = 25 degrees C
      while monitoring the extent of relaxation and heat capacity change as a function
      of time via MTDSC. Configurational thermodynamic quantities (Gc, Hc, and Sc) and
      molecular relaxation time constants, tau, were calculated from the calorimetric
      data. Interestingly, the Gibbs free energy driving force for crystallization was
      nearly identical for the two compounds. The largest differences were found in the
      configurational entropy (Sc) values for the fresh glasses and in the Sc values
      over time. Configurational entropy values were approximately 50% higher for
      ritonavir. The tau values of freshly prepared glasses indicated that both
      materials had similar initial mobility at the annealing temperatures and the
      temperature dependence of tau was approximately Arrhenius, regardless of age.
      Although initial tau values were similar, the tau values after 3 days annealing
      were approximately sixfold greater for ritonavir. The relatively poor physical
      stability of nifedipine compared to ritonavir is attributed to both the lower
      entropic barrier to crystallization for fresh and annealed glass, and higher
      molecular mobility in aged glasses of nifedipine. These observations below Tg are
      consistent with the previous work on physical stability of amorphous
      pharmaceuticals performed above Tg.

PMID- 17031847
TI  - Calcium signaling in non-excitable cells: Ca2+ release and influx are independent
      events linked to two plasma membrane Ca2+ entry channels.
AB  - The regulatory mechanism of Ca2+ influx into the cytosol from the extracellular
      space in non-excitable cells is not clear. The "capacitative calcium entry" (CCE)
      hypothesis suggested that Ca2+ influx is triggered by the IP(3)-mediated emptying
      of the intracellular Ca2+ stores. However, there is no clear evidence for CCE and
      its mechanism remains elusive. In the present work, we have provided the reported
      evidences to show that inhibition of IP(3)-dependent Ca2+ release does not affect
      Ca2+ influx, and the experimental protocols used to demonstrate CCE can stimulate
      Ca2+ influx by means other than emptying of the Ca2+ stores. In addition, we have
      presented the reports showing that IP(3)-mediated Ca2+ release is linked to a
      Ca2+ entry from the extracellular space, which does not increase cytosolic [Ca2+]
      prior to Ca2+ release. Based on these and other reports, we have provided a model
      of Ca2+ signaling in non-excitable cells, in which IP(3)-mediated emptying of the
      intracellular Ca2+ store triggers entry of Ca2+ directly into the store, through
      a plasma membrane TRPC channel. Thus, emptying and direct refilling of the Ca2+
      stores are repeated in the presence of IP(3), giving rise to the transient phase
      of oscillatory Ca2+ release. Direct Ca2+ entry into the store is regulated by its
      filling status in a negative and positive manner through a Ca2+ -binding protein
      and Stim1/Orai complex, respectively. The sustained phase of Ca2+ influx is
      triggered by diacylglycerol (DAG) through the activation of another TRPC channel,
      independent of Ca2+ release. The plasma membrane IP(3) receptor (IP(3)R) plays an
      essential role in Ca2+ influx, by interacting with the DAG-activated TRPC,
      without the requirement of binding to IP(3).

PMID- 17031848
TI  - Oxysterol-induced osteoblastic differentiation of pluripotent mesenchymal cells
      is mediated through a PKC- and PKA-dependent pathway.
AB  - Oxysterols form a large family of oxygenated derivatives of cholesterol that are
      present in circulation, and in human and animal tissues. The discovery of
      osteoinductive molecules that can induce the lineage-specific differentiation of
      cells into osteoblastic cells and therefore enhance bone formation is crucial for
      better management of bone fractures and osteoporosis. We previously reported that
      specific oxysterols have potent osteoinductive properties and induce the
      osteoblastic differentiation of pluripotent mesenchymal cells. In the present
      report we demonstrate that the induction of osteoblastic differentiation by
      oxysterols is mediated through a protein kinase C (PKC)- and protein kinase A
      (PKA)-dependent mechanism(s). Furthermore, oxysterol-induced-osteoblastic
      differentiation is marked by the prolonged DNA-binding activity of Runx2 in M2
      10B4 bone marrow stromal cells (MSCs) and C3H10T1/2 embryonic fibroblastic cells.
      This increased activity of Runx2 is almost completely inhibited by PKC inhibitors
      Bisindolylmaleimide and Rottlerin, and only minimally inhibited by PKA inihibitor
      H-89. PKC- and PKA-dependent mechanisms appear to also regulate other markers of
      osteoblastic differentiation including alkaline phosphatase (ALP) activity and
      osteocalcin mRNA expression in response to oxysterols. Finally, osteogenic
      oxysterols induce osteoblastic differentiation with BMP7 and BMP14 in a
      synergistic manner as demonstrated by the enhanced Runx2 DNA-binding activity,
      ALP activity, and osteocalcin mRNA expression. Since Runx2 is an indispensable
      factor that regulates the differentiation of osteoblastic cells and bone
      formation in vitro and in vivo, its increased activity in oxysterol-treated cells
      further validates the potential role of oxysterols in lineage-specific
      differentiation of pluripotent mesenchymal cells and their potential therapeutic
      use as bone anabolic factors.

PMID- 17031849
TI  - Apoptosis induced by all-trans retinoic acid in N-acetylglucosaminyltransferase V
      repressed human hepatocarcinoma cells is mediated through endoplasmic reticulum
      stress.
AB  - We previously demonstrated that endoplasmic reticulum (ER) stress was triggered
      in human hepatocarcinoma 7721 cells transfected with antisense cDNA of N
      acetylglucosaminyltransferase V (GnT-V-AS/7721) which were more susceptible to
      apoptosis induced by all-trans retinoic acid (ATRA). In the present study, we
      report that ATRA-induced apoptosis in GnT-V-AS/7721 cells is mediated through ER
      stress. We show here that ER stress is enhanced in GnT-V-AS/7721 cells with 80
      microM ATRA treatment for 24 h, which is evidenced by the increase of GRP78/Bip,
      C/EBP-homologous protein-10 (CHOP, also known as GADD153) and spliced XBP1.
      Additionally, activation of caspase-12, caspase-9, and -3 was detected, and
      apoptosis morphology was observed in GnT-V-AS/7721 cells with ATRA treatment.
      These results suggest that ATRA enhances the ER stress triggered in GnT-V-AS/7721
      cells, which represents a novel mechanism of ATRA to induce apoptosis. We further
      observed that GnT-V was significantly repressed and the structure of N-glycans
      was changed in GnT-V-AS/7721 cells with 80 microM ATRA treatment for 24 h,
      suggesting that repression of GnT-V by ATRA causes the enhanced ER stress and ER
      stress-mediated apoptosis in GnT-V-AS/7721 cells.

PMID- 17031850
TI  - Differential regulation of cyclooxygenase-2 and inducible nitric oxide synthase
      by 4-hydroxynonenal in human osteoarthritic chondrocytes through ATF-2/CREB-1
      transactivation and concomitant inhibition of NF-kappaB signaling cascade.
AB  - 4-hydroxynonenal (HNE), a lipid peroxidation end product, is produced abundantly
      in osteoarthritic (OA) articular tissues and was recently identified as a potent
      catabolic factor in OA cartilage. In this study, we provide additional evidence
      that HNE acts as an inflammatory mediator by elucidating the signaling cascades
      targeted in OA chondrocytes leading to cyclooxygenase-2 (COX-2) and inducible
      nitric oxide synthase (iNOS) gene expression. HNE induced COX-2 protein and mRNA
      levels with accompanying increases in prostaglandin E2 (PGE(2)) production. In
      contrast, HNE had no effect on basal iNOS expression or nitric oxide (NO)
      release. However, HNE strongly inhibited IL-1beta-induced iNOS or NO production.
      Transient transfection experiments revealed that the ATF/CRE site (-58/-53) is
      essential for HNE-induced COX-2 promoter activation and indeed HNE induced ATF-2
      and CREB-1 phosphorylation as well as ATF/CRE binding activity. Overexpression of
      p38 MAPK enhanced the HNE-induced ATF/CRE luciferase reporter plasmid activation,
      COX-2 synthesis and promoter activity. HNE abrogated IL-1beta-induced iNOS
      expression and promoter activity mainly through NF-kappaB site (-5,817/-5,808)
      possibly via suppression of IKKalpha-induced IkappaBalpha phosphorylation and NF
      kappaB/p65 nuclear translocation. Upon examination of upstream signaling
      components, we found that IKKalpha was inactivated through HNE/IKKalpha adduct
      formation. Taken together, these findings illustrate the central role played by
      HNE in the regulation of COX-2 and iNOS in OA. The aldehyde induced selectively
      COX-2 expression via ATF/CRE activation and inhibited iNOS via IKKalpha
      inactivation.

PMID- 17031851
TI  - Association of p65 and C/EBPbeta with HIV-1 LTR modulates transcription of the
      viral promoter.
AB  - In human immunodeficiency virus type 1 (HIV-1) latently infected cells, NF-kappaB
      (NF-kappaB) plays a critical role in the transcriptional induction of the HIV-1
      promoter. The trans-activating ability of NF-kappaB can be modified by another
      nuclear factor C/EBPbeta that can physically bind to NF-kappaB and regulate its
      activity. Because the HIV-1 promoter also contains a C/EBPbeta site adjacent to
      the NF-kappaB site, the present study examined cooperative functional in vivo
      interaction of the p65 subunit of NF-kappaB and C/EBPbeta, and the impact of Tat
      in this event. We demonstrated that ectopic expression of p65 along with Tat
      increases p65 binding to HIV-1 LTR, and that this increase correlates with
      enhanced HIV-1 promoter activity. Further, co-expression of C/EBPbeta and Tat
      leads to a decrease in p65 binding, which allows C/EBPbeta to bind more
      efficiently to the LTR. Inhibition of p65 expression by siRNA significantly
      decreases C/EBPbeta-binding and LTR expression. Using ChIP assay, we confirmed
      the existence of an interchange between p65 and C/EBPbeta and their abilities to
      bind to the LTR in vivo. These observations demonstrate that a delicate balance
      of interaction between p65, C/EBPbeta, and Tat can dictate the level of HIV-1 LTR
      transcription.

PMID- 17031852
TI  - Apoptosis as a possible mechanism of infertility in Echinococcus granulosus
      hydatid cysts.
AB  - Echinococcus granulosus is a parasitic cestode causing hydatidosis in
      intermediate hosts (human and herbivorous). Most symptoms of the disease occur by
      the pressure exerted on viscera by cysts that are formed upon ingestion of the
      parasite eggs excreted by definitive hosts (canines). Protoscoleces, the
      developmental form of the parasite infective to definitive hosts, are formed in
      the germinal nucleated layer of fertile hydatid cysts. For unknown reasons, some
      cysts are unable to produce protoscoleces (infertile hydatid cysts). In this
      study, analysis of DNA fragmentation using TUNEL and agarose gel electrophoresis
      showed higher levels of apoptosis in infertile cysts as compared to fertile
      cysts. Additionally, caspase 3 was detected both in fertile and infertile cysts;
      the activity of this enzyme was found to be higher in infertile cysts. We
      conclude that apoptosis may be involved in hydatid cyst infertility. This is the
      first report on the presence of programmed cell death in E. granulosus.

PMID- 17031853
TI  - Prostaglandin E2 downregulates TNF-alpha-induced production of matrix
      metalloproteinase-1 in HCS-2/8 chondrocytes by inhibiting Raf-1/MEK/ERK cascade
      through EP4 prostanoid receptor activation.
AB  - Matrix metalloproteinase-1 (MMP-1, collagenase-1) plays a pivotal role in the
      process of joint destruction in degenerative joint diseases. We have examined the
      regulation of MMP-1 production in human chondrocytic HCS-2/8 cells stimulated by
      tumor necrosis factor-alpha (TNF-alpha). In response to TNF-alpha, MMP-1 is
      induced and actively released from HCS-2/8 cells. The induction of MMP-1
      expression correlates with activation of ERK1/2, MEK, and Raf-1, and is potently
      prevented by U0126, a selective inhibitor of MEK1/2 activation. In contrast,
      SB203580, a selective p38 mitogen-activated protein kinases (MAPK) inhibitor, had
      no effects on TNF-alpha-induced MMP-1 release. A serine/threonine kinase, Akt was
      not activated in TNF-alpha-stimulated HCS-2/8 cells. TNF-alpha stimulated the
      production of PGE(2) in addition to MMP-1 in HCS-2/8 cells. Exogenously added
      PGE(2) potently inhibited TNF-alpha-induced both MMP-1 production and activation
      of ERK1/2. The effects of PGE(2) were mimicked by ONO-AE1-329, a selective EP4
      receptor agonist but not by butaprost, a selective EP2 agonist. In contrast,
      blockade of endogenously produced PGE(2) signaling by ONO-AE3-208, a selective
      EP4 receptor antagonist, enhanced TNF-alpha-induced MMP-1 production.
      Furthermore, the suppression of MMP-1 production by exogenously added PGE(2) was
      reversed by ONO-AE3-208. Activation of EP4 receptor resulted in cAMP-mediated
      phosphorylation of Raf-1 on Ser259, a negative regulatory site, and blocked
      activation of Raf-1/MEK/ERK cascade. Taken together, these findings indicate that
      Raf-1/MEK/ERK signaling pathway plays a crucial role in the production of MMP-1
      in HCS-2/8 cells in response to TNF-alpha, and that the produced PGE(2)
      downregulates the expression of MMP-1 by blockage of TNF-alpha-induced Raf-1
      activation through EP4-PGE(2) receptor activation.

PMID- 17031854
TI  - TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapy that
      preferentially induces apoptosis in cancer cells. However, many neoplasms are
      resistant to TRAIL by mechanisms that are poorly understood. Here we demonstrated
      that human prostate cancer cells, but not normal prostate cells, are dramatically
      sensitized to TRAIL-induced apoptosis and caspase activation by quercetin.
      Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the
      proliferation of cancer cells. We have shown that quercetin can potentiate TRAIL
      induced apoptotic death. Human prostate adenocarcinoma DU-145 and LNCaP cells
      were treated with various concentrations of TRAIL (10-200 ng/ml) and/or quercetin
      (10-200 microM) for 4 h. Quercetin, which caused no cytotoxicity by itself,
      promoted TRAIL-induced apoptosis. The TRAIL-mediated activation of caspase, and
      PARP (poly(ADP-ribose) polymerase) cleavage were both enhanced by quercetin.
      Western blot analysis showed that combined treatment with TRAIL and quercetin did
      not change the levels of TRAIL receptors (death receptors DR4 and DR5, and DcR2
      (decoy receptor 2)) or anti-apoptotic proteins (FLICE-inhibitory protein (FLIP),
      inhibitor of apoptosis (IAP), and Bcl-2). However, quercetin promoted the
      dephosphorylation of Akt. Quercetin-induced potent inhibition of Akt
      phosphorylation. Taken together, the present studies suggest that quercetin
      enhances TRAIL-induced cytotoxicity by activating caspases and inhibiting
      phosphorylation of Akt.

PMID- 17031855
TI  - Osteoblasts and osteocytes respond differently to oscillatory and unidirectional
      fluid flow profiles.
AB  - Bone cells subjected to mechanical loading by fluid shear stress undergo
      significant architectural and biochemical changes. The models of shear stress
      used to analyze the effects of loading bone cells in vitro include both
      oscillatory and unidirectional fluid shear profiles. Although the fluid flow
      profile experienced by cells within bone is most likely oscillatory in nature, to
      date there have been few direct comparisons of how bone cells respond to these
      two fluid flow profiles. In this study we evaluated morphologic and biochemical
      responses to a time course of unidirectional and oscillatory fluid flow in two
      commonly used bone cell lines, MC3T3-E1 osteoblasts and MLO-Y4 osteocytes. We
      determined that stress fibers formed and aligned within osteoblasts after 1 h of
      unidirectional fluid flow, but this response was not observed until greater than
      5 h of oscillatory fluid flow. Despite the delay in stress fiber formation,
      oscillatory and unidirectional fluid flow profiles elicited similar temporal
      effects on the induction of both cyclooxygenase-2 (Cox-2) and osteopontin protein
      expression in osteoblasts. Interestingly, MLO-Y4 osteocytes formed organized
      stress fibers after exposure to 24 h of unidirectional shear stress, while the
      number of dendritic processes per cell increased along with Cox-2 protein levels
      after 24 h of oscillatory shear stress. Despite these differences, both flow
      profiles significantly altered osteopontin levels in MLO-Y4 osteocytes. Together
      these results demonstrate that the profile of fluid shear can induce
      significantly different responses from osteoblasts and osteocytes.

PMID- 17031856
TI  - Static strain stimulates expression of matrix metalloproteinase-2 and VEGF in
      microvascular endothelium via JNK- and ERK-dependent pathways.
AB  - VEGF and MMP protein production are both required for exercise-induced capillary
      growth in skeletal muscle. The underlying process by which muscle activity
      initiates an angiogenic response is not established, but it is known that
      mechanical forces such as muscle stretch are involved. We hypothesized that
      stretch of skeletal muscle microvascular endothelial cells induces production of
      MMP-2 and VEGF through a common signal pathway. Endothelial cells were grown on
      Bioflex plates and exposed to 10% static stretch for up to 24 h. MMP-2 protein
      level was measured by gelatin zymography and VEGF, MMP-2, and MT1-MMP mRNA levels
      were quantified by real-time quantitative PCR. ERK1/2 and JNK phosphorylation and
      VEGF protein levels were assessed by Western blotting. Effects of mitogen
      activated protein kinases (MAPKs) (ERK1/2, JNK) and reactive oxygen species (ROS)
      on stretch-induced expression of MMP-2 and VEGF were tested using pharmacological
      inhibitors. Stretching of endothelial cells for 24 h caused significant increases
      in MMP-2 protein and mRNA level, but no change in MT1-MMP mRNA. While MMP-2
      protein production was enhanced by H(2)O(2) in unstretched cells, ROS inhibition
      during stretch did not diminish MMP-2 mRNA or protein production. Inhibition of
      JNK suppressed stretch-induced MMP-2 protein and mRNA, but inhibition of ERK had
      no effect. In contrast, inhibition of ERK but not JNK attenuated the stretch
      induced increase in VEGF mRNA. Our results demonstrate that differential
      regulation of MMP-2 and VEGF by MAPK signal pathways contribute to stretch
      induced activation of microvascular endothelial cells.

PMID- 17031858
TI  - Prolyl-hydroxylase inhibition and HIF activation in osteoblasts promotes an
      adipocytic phenotype.
AB  - Bone is a dynamic environment where cells sense and adapt to changes in nutrient
      and oxygen availability. Conditions associated with hypoxia in bone are also
      associated with bone loss. In vitro hypoxia (2% oxygen) alters gene expression in
      osteoblasts and osteocytes and induces cellular changes including the
      upregulation of hypoxia inducible factor (HIF) levels. Our studies show that
      osteoblasts respond to hypoxia (2% oxygen) by enhancing expression of genes
      associated with adipocyte/lipogenesis phenotype (C/EBPbeta, PPARgamma2, and aP2)
      and by suppressing expression of genes associated with osteoblast differentiation
      (alkaline phosphatase, AP). Hypoxia increased HIF protein levels, hypoxic
      response element (HRE) binding, and HRE-reporter activity. We also demonstrate
      that prolyl-hydroxylases 2 and 3 (PHD2, PHD3), one of the major factors
      coordinating HIF degradation under normoxic but not hypoxic conditions, are
      induced in osteoblasts under hypoxic conditions. To further determine the
      contribution of PHDs and upregulated HIF activity in modulating osteoblast
      phenotype, we treated osteoblasts with a PHD inhibitor, dimethyloxaloylglycine
      (DMOG), and maintained cells under normoxic conditions. Similar to hypoxic
      conditions, HRE reporter activity was increased and adipogenic gene expression
      was increased while osteoblastic genes were suppressed. Taken together, our
      findings indicate a role for PHDs and HIFs in the regulation of osteoblast
      phenotype.

PMID- 17031857
TI  - (--)-epigallocatechin gallate enhances prostaglandin F2alpha-induced VEGF
      synthesis via upregulating SAPK/JNK activation in osteoblasts.
AB  - Catechin, one of the major flavonoids presented in plants such as tea, reportedly
      suppresses bone resorption. We previously reported that prostaglandin F(2alpha)
      (PGF(2alpha)) stimulates the synthesis of vascular endothelial growth factor
      (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like
      MC3T3-E1 cells. To clarify the mechanism of catechin effect on osteoblasts, we
      investigated the effect of (--)-epigallocatechin gallate (EGCG), one of the major
      green tea flavonoids, on the VEGF synthesis by PGF(2alpha) in MC3T3-E1 cells. The
      PGF(2alpha)-induced VEGF synthesis was significantly enhanced by EGCG. The
      amplifying effect of EGCG was dose dependent between 10 and 100 microM. EGCG did
      not affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase.
      SB203580, a specific inhibitor of p38 MAP kinase, and SP600125, a specific
      inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK),
      reduced the PGF(2alpha)-induced VEGF synthesis. EGCG markedly enhanced the
      phosphorylation of SAPK/JNK induced by PGF(2alpha) without affecting the
      PGF(2alpha)-induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced
      the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the
      PGF(2alpha)-induced phosphorylation of c-Jun was amplified by EGCG. These results
      strongly suggest that EGCG upregulate PGF(2alpha)-stimulated VEGF synthesis
      resulting from amplifying activation of SAPK/JNK in osteoblasts.

PMID- 17031859
TI  - Investigation of drying stresses on proteins during lyophilization:
      differentiation between primary and secondary-drying stresses on lactate
      dehydrogenase using a humidity controlled mini freeze-dryer.
AB  - This article describes the design, performance testing, and application of a
      controlled humidity mini-freeze-dryer in studying the physical stability of
      lactate dehydrogenase during lyophilization. Performance evaluation of the mini
      freeze-dryer was conducted with tests, namely water sublimation, radiation heat
      exchange, lowest achievable temperature, and leak testing. Protein stability
      studies were conducted by comparing protein activity at various stages of
      lyophilization with the initial activity. The shelf and condenser temperature
      were stable at <-40 degrees C, wall temperature was within 2 degrees C of the
      shelf temperature, and the leak rate was small. The chamber pressure was
      controlled by the ice on the condenser and the product temperature during
      sublimation was equal to the shelf temperature. Addition of Tween 80 prevented
      activity loss in solution and after freeze-thaw. No activity loss was observed
      after primary-drying even in absence of lyoprotectants and with collapse of cake
      structure. Five percent (w/w) sucrose concentration was required to achieve full
      stabilization. In conclusion, performance testing established that the mini
      freeze-dryer was suitable for mechanistic freeze-drying studies. Secondary-drying
      was the critical step for protein stability. The concentration of sucrose
      required to stabilize the protein completely was several orders of magnitude
      higher than that required to satisfy the direct interaction requirement of the
      protein.

PMID- 17031860
TI  - Effects of Kaempferia parviflora extracts and their flavone constituents on P
      glycoprotein function.
AB  - The purpose of this study was to examine the effects of extracts and flavone
      derivatives from the rhizome of Kaempferia parviflora on P-glycoprotein (P-gp)
      mediated transport in LLC-GA5-COL150, a transfectant cell line of a porcine
      kidney epithelial cell line LLC-PK1 with human MDR1 cDNA. Ethanol extract
      obtained from Kaempferia parviflora rhizome significantly increased the
      accumulation of rhodamine 123 and daunorubicin, P-gp substrates, in LLC-GA5
      COL150 cells, but not in LLC-PK1 cells. The aqueous extract also increased the
      accumulation in LLC-GA5-COL150 cells with lower potency than the ethanol extract.
      The effects of flavone derivatives isolated from the rhizome of Kaempferia
      parviflora on P-gp function were examined. Among six flavones tested, 3,5,7,3',4'
      pentamethoxyflavone most potently increased the accumulation of rhodamine 123 and
      daunorubicin in LLC-GA5-COL150 cells in a concentration-dependent manner. In
      addition, 5,7-dimethoxyflavone to lesser degree increased rhodamine 123
      accumulation in LLC-GA5-COL150 cells. In contrast, the other four flavone
      derivatives had no significant effect on the accumulation of rhodamine 123 in LLC
      GA5-COL150 cells in a concentration range tested. These results indicate that
      extracts and flavone derivatives from the rhizome of Kaempferia parviflora can
      inhibit P-gp function, which may be useful for overcoming P-gp-mediated multidrug
      resistance and improving the oral bioavailability of anticancer agents.

PMID- 17031861
TI  - Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine
      anterior cruciate ligament.
AB  - The anterior cruciate ligament (ACL) fails to heal after suture repair. One
      hypothesis for this failure is the premature loss of the fibrin clot, or
      provisional scaffolding, between the two ligament ends in the joint environment.
      To test this hypothesis, a substitute provisional scaffold of collagen-platelet
      rich plasma (PRP) hydrogel was used to fill the ACL wound site at the time of
      suture repair and the structural properties of the healing ACLs evaluated 4 weeks
      after surgery. Bilateral ACL transections were performed in five 30-kg Yorkshire
      pigs and treated with suture repair. In each animal, one of the repairs was
      augmented with placement of a collagen-PRP hydrogel at the ACL transection site,
      while the contralateral knee had suture repair alone. In addition, six control
      knees with intact ACLs from three additional animals were used as a control
      group. No postoperative immobilization was used. After 4 weeks the animals
      underwent in vivo magnetic resonance imaging to assess the size of the healing
      ACL, followed by biomechanical testing to determine tensile properties. The
      supplementation of suture repair with a collagen-PRP hydrogel resulted in
      significant improvements in load at yield, maximum load, and linear stiffness at
      4 weeks. We conclude that use of a stabilized provisional scaffold, such as a
      collagen-PRP hydrogel, to supplement primary repair of the ACL can result in
      improved biomechanical properties at an early time point. Further studies to
      determine the long-term effect of primary repair enhancement are needed.

PMID- 17031862
TI  - An unusual arterial connection between the celiac trunk and the gastroduodenal
      artery.

PMID- 17031863
TI  - An unusual course of the left recurrent laryngeal nerve.
AB  - Variation in the course of the left recurrent laryngeal nerve is seemingly very
      rare. During the routine dissection of an adult male cadaver, the entire left
      recurrent laryngeal nerve after branching from the left vagus nerve was noted to
      travel medial to the ligamentum arteriosum. We hypothesize that this rare
      variation may occur, if the left recurrent laryngeal nerve passes inferior to the
      fifth rather than the sixth aortic arch during embryological development. As our
      case report demonstrates, the relationship between the ligamentum arteriosum and
      the left recurrent laryngeal nerve is not absolute. Although seemingly rare,
      cardiothoracic surgeons must consider variations of the left recurrent laryngeal
      nerve during surgical procedures in the region of the ligamentum arteriosum in
      order to minimize potential postoperative complications.

PMID- 17031864
TI  - Bilateral tibial hemimelia I.
AB  - Congenital absence of tibia is a rare anomaly. We report a case of bilateral
      tibial hemimelia born to phenotypically normal parents. The two amputated legs
      with tibial dysplasia obtained from a 3-year-old boy were studied by radiography
      and anatomical dissection. The radiological evaluation revealed a normal hip
      joint. The lower end of femur was normal without any bifurcation, shortening or
      bowing. Fibula was present on both legs and there was no sign of bowing or
      doubling. Both right and left tibiae were absent. In addition, on the right side,
      five tarsal bones, two metatarsals and the corresponding digital rays were
      absent. On the left side, three tarsal bones were absent. Dissection of the
      amputated segments showed the presence of extensor digitorum longus, peroneus
      tertius, peroneus longus and brevis, gastrocnemius, and soleus. Following
      bilateral knee disarticulation the patient was fitted with prosthesis and is
      doing well.

PMID- 17031865
TI  - p53 modulation of the DNA damage response.
AB  - The tumor suppressor p53 plays a central role in the DNA damage response. After
      exposure to genotoxic stress, p53 can both positively and negatively regulate
      cell fate. Initially, p53 promotes cell survival by inducing cell cycle arrest,
      DNA repair, and other pro-survival pathways. However, when cells accumulate DNA
      damage or demonstrate aberrant growth, p53 can direct the elimination of damaged
      cells. In this review, we will discuss the transcriptional-dependent and 
      independent roles of p53 in regulating the DNA damage response.

PMID- 17031866
TI  - Flow characterization of a wavy-walled bioreactor for cartilage tissue
      engineering.
AB  - Cartilage tissue engineering requires the use of bioreactors in order to enhance
      nutrient transport and to provide sufficient mechanical stimuli to promote
      extracellular matrix (ECM) synthesis by chondrocytes. The amount and quality of
      ECM components is a large determinant of the biochemical and mechanical
      properties of engineered cartilage constructs. Mechanical forces created by the
      hydrodynamic environment within the bioreactors are known to influence ECM
      synthesis. The present study characterizes the hydrodynamic environment within a
      novel wavy-walled bioreactor (WWB) used for the development of tissue-engineered
      cartilage. The geometry of this bioreactor provides a unique hydrodynamic
      environment for mammalian cell and tissue culture, and investigation of
      hydrodynamic effects on tissue growth and function. The flow field within the WWB
      was characterized using two-dimensional particle-image velocimetry (PIV). The
      flow in the WWB differed significantly from that in the traditional spinner flask
      both qualitatively and quantitatively, and was influenced by the positioning of
      constructs within the bioreactor. Measurements of velocity fields were used to
      estimate the mean-shear stress, Reynolds stress, and turbulent kinetic energy
      components in the vicinity of the constructs within the WWB. The mean-shear
      stress experienced by the tissue-engineered constructs in the WWB calculated
      using PIV measurements was in the range of 0-0.6 dynes/cm2. Quantification of the
      shear stress experienced by cartilage constructs, in this case through PIV, is
      essential for the development of tissue-growth models relating hydrodynamic
      parameters to tissue properties.

PMID- 17031867
TI  - Effect of ionic crosslinking on the drug release properties of chitosan diacetate
      matrices.
AB  - Chitosan diacetate (CDA) was prepared by alkylating the amino moieties of
      chitosan with mono-iodoacetic acid. Subsequently, CDA was cross-linked with Al3+,
      Zn2+, and Ca2+ ions to yield three ionotropically crosslinked polymeric matrices.
      These composite matrices were characterized employing infrared spectroscopy (IR)
      and differential scanning calorimetry (DSC). Subsequently, they were loaded with
      caffeine, as a model drug, and were assessed as sustained release carriers by
      evaluating their caffeine release profiles. Interestingly, only CDA-Zn2+ complex
      sustained the release of caffeine effectively in a zero-order manner. The drug
      release and thermal behavior of the tested matrices agree with the relative
      strength of the ionic or coordination character of the bonds. This, in turn,
      depends on the position of the complexing ions on the electrophilic
      softness/hardness scale.

PMID- 17031868
TI  - Tutorial in biostatistics: competing risks and multi-state models.
AB  - Standard survival data measure the time span from some time origin until the
      occurrence of one type of event. If several types of events occur, a model
      describing progression to each of these competing risks is needed. Multi-state
      models generalize competing risks models by also describing transitions to
      intermediate events. Methods to analyze such models have been developed over the
      last two decades. Fortunately, most of the analyzes can be performed within the
      standard statistical packages, but may require some extra effort with respect to
      data preparation and programming. This tutorial aims to review statistical
      methods for the analysis of competing risks and multi-state models. Although some
      conceptual issues are covered, the emphasis is on practical issues like data
      preparation, estimation of the effect of covariates, and estimation of cumulative
      incidence functions and state and transition probabilities. Examples of analysis
      with standard software are shown.

PMID- 17031869
TI  - Optimization of the hydrochloric acid concentration used for trifluoroacetate
      removal from synthetic peptides.
AB  - Trifluoroacetate (CF3COO-, or TFA) is almost always present in commercially
      synthesized peptides. Unfortunately, it has a strong infrared (IR) absorption
      band at 1673 cm-1, significantly overlapping or even completely obscuring the
      amide I band of a peptide. In such cases TFA must be removed from the solution in
      order to be able to use IR absorption spectroscopy for peptide secondary
      structure determination. The most convenient and widely used procedure involves
      peptide lyophilization from a 0.1 M HCl solution. In our studies of the
      tryptophan-rich antimicrobial peptide indolicidin, we have found that caution
      should be taken when using this HCl concentration. High HCl concentrations (>10
      mM in unbuffered solutions and > 50 mM in buffered solutions) may modify the
      peptide structure and reduce its thermal stability, thereby interfering with
      subsequent structural investigations of the peptide. Our results indicate that
      HCl concentrations between 2 and 10 mM are adequate to remove essentially all TFA
      impurities without any modification of the peptide secondary structure.

PMID- 17031870
TI  - Studies on deprotection of cysteine and selenocysteine side-chain protecting
      groups.
AB  - We present here a simple method for deprotecting p-methoxybenzyl groups and
      acetamidomethyl groups from the side-chains of cysteine and selenocysteine. This
      method uses the highly elecrophilic, aromatic disulfides 2,2'-dithiobis(5
      nitropyridine) (DTNP) and 2,2'-dithiodipyridine (DTP) dissolved in TFA to effect
      removal of these heretofore difficult-to-remove protecting groups. The
      dissolution of these reagents in TFA, in fact, serves to 'activate' them for the
      deprotection reaction because protonation of the nitrogen atom of the pyridine
      ring makes the disulfide bond more electrophilic. Thus, these reagents can be
      added to any standard cleavage cocktail used in peptide synthesis.The p
      methoxybenzyl group of selenocysteine is easily removed by DTNP. Only sub
      stoichiometric amounts of DTNP are required to cause full removal of the p
      methoxybenzyl group, with as little as 0.2 equivalents necessary to effect 70%
      removal of the protecting group. In order to remove the p-methoxybenzyl group
      from cysteine, 2 equivalents of DTNP and the addition of thioanisole was required
      to effect removal. Thioanisole was absolutely required for the reaction in the
      case of the sulfur-containing amino acids, while it was not required for
      selenocysteine. The results were consistent with thioanisole acting as a
      catalyst. The acetamidomethyl group of cysteine could also be removed using DTNP,
      but required the addition of > 15 equivalents to be effective. DTP was less
      robust as a deprotection reagent. We also demonstrate that this chemistry can be
      used in a simultaneous cyclization/deprotection reaction between selenocysteine
      and cysteine residues protected by p-methoxybenzyl groups to form a
      selenylsulfide bond, demonstrating future high utility of the deprotection
      method.

PMID- 17031871
TI  - Bombesin analogs containing alpha-amino-isobutyric acid with potent anticancer
      activity.
AB  - Six octapeptide bombesin (BN) analogs were synthesized by substituting alpha
      aminoisobutyric acid (Aib), in place of Ala9 or Gly11, or both, in the [D-Phe6,
      desMet14]-BN (6-14) sequence: D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13-NH2
      (P0). Additionally, Leu13 was replaced with isoleucine in two analogs and one of
      the analogs was butanoylated at the N-terminus. The antiproliferative activity of
      the analogs was tested in vitro on human pancreatic (MiaPaCa-2) and colon cancer
      (SW620, HT29 and PTC) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The analogs demonstrated anticancer
      activity in the above cell lines at concentrations ranging from 0.01 nM to 1
      microM. One of the analogs, P6, was evaluated for in vivo tumor regression in a
      xenograft model of human primary colon cancer in athymic nude mice and was found
      to cause significant reduction in tumor volume. NMR and molecular dynamics (MD)
      simulation studies for this analog revealed the presence of a mixed 3(10)/alpha
      helical structure. This study demonstrates that the designed BN analogs retain
      their anticancer activity after the incorporation of the constrained amino acid,
      Aib, and are potential molecules for future use in cancer therapy and drug
      targeting.

PMID- 17031872
TI  - Prenatal screening for congenital heart disease with four-chamber and outflow
      tract views: a multicenter study.
AB  - OBJECTIVE: Congenital heart diseases (CHD) are the most common congenital
      anomalies, and most cases occur in the low-risk population. Prenatal ultrasound
      screening based on visualization of the four-chamber view has had disappointing
      results in detecting these anomalies thus far. The aim of this study was to
      evaluate the diagnostic accuracy of ultrasound screening based on the combination
      of the four-chamber and outflow-tract views. METHODS: We conducted a multicenter
      prospective observational study in 15 obstetric units in the Piedmont Region,
      Italy. All operators received specific training. Data were recorded regarding
      visualization of the four-chamber view and the outflow tracts at each routine
      scan in pregnancies without any risk factor. When an anomaly was suspected, the
      patient was sent to the referral center. We obtained the follow-up data of the
      newborns until discharge from hospital and calculated the diagnostic accuracy of
      the test. RESULTS: 9074 ultrasound scans were performed on 7041 women and
      complete follow-up information was available for 6368 of them. Fifty-eight cases
      of CHD were observed at birth or postmortem (prevalence 9.1 per thousand); 38 of
      them were diagnosed in utero. The sensitivity of the test was 65.5%, the
      specificity 99.7%, the positive predictive value 70.4% and the negative
      predictive value 99.7%. The sensitivity of the four-chamber view alone was 60.3%.
      CONCLUSIONS: The sensitivity was significantly higher than that in a similar
      study performed in 1997 in the same setting. This improvement can be attributed
      in part to extension of the examination to the outflow-tract view, but also to
      technological developments and better training of the operators.

PMID- 17031873
TI  - Successful treatment of a recurrent Cesarean scar ectopic pregnancy by surgical
      repair of the uterine defect.

PMID- 17031874
TI  - Serum biochemistry correlates with the size of tubal ectopic pregnancy on
      sonography.
AB  - OBJECTIVE: To investigate whether there is a correlation between serum
      biochemistry (human chorionic gonadotropin (hCG), CA 125, progesterone and
      estradiol) and the common sonographic findings (blob sign, bagel sign or
      extrauterine gestational sac with cardiac activity) or size of a tubal ectopic
      pregnancy, and whether there is a difference in serum biochemistry between women
      with a tubal ectopic pregnancy who are hemodynamically unstable (tachycardia,
      hypotension, falling hemoglobin levels and/or acute severe abdominal pain) and
      those who are hemodynamically stable. METHODS: This was a prospective cohort
      study of 106 women with a tubal ectopic pregnancy. We noted transvaginal
      ultrasound examination findings including adnexal mass size, and the serum levels
      of hCG, CA 125, progesterone and estradiol. The data were analyzed
      retrospectively. RESULTS: The mean maternal and gestational ages were 30.7+/-5.7
      years and 44+/-4.2 days, respectively. There was no correlation between serum
      markers and common sonographic findings. However, in the presence of the bagel
      sign on ultrasound, hemodynamic stability was more common (P=0.03). The mean
      serum hCG concentrations in tubal ectopic pregnancies<20 mm, 20-40 mm and >40 mm
      in size were 2225.3+/-3166.9, 4124.8+/-6121.4, and 11 011.8+/-12 670.1 IU/mL,
      respectively (P<0.001). Serum hCG, CA 125 and estradiol values were well
      correlated with adnexal mass size; for CA 125 this correlation was linear. There
      was no difference in serum biochemistry between hemodynamically stable and
      hemodynamically unstable women. CONCLUSION: Common sonographic findings of tubal
      ectopic pregnancy do not correlate with serum biochemistry. High levels of CA
      125, hCG or estradiol may suggest a larger adnexal mass in women with
      uncomplicated tubal pregnancies. Hemodynamically stable and hemodynamically
      unstable women do not differ in their serum biochemistry.

PMID- 17031875
TI  - Insect gonadotropic peptide hormones: some recent developments.
AB  - Gonadotropic peptides are a new generation of peptide hormone regulators of
      insect reproduction. They have been isolated from ovaries, oviducts, or brains of
      insects. The subject of this paper is insect peptides that exert stimulatory or
      inhibitory effects on ovarian development and oocyte maturation. On the basis of
      the literature data and the results of our investigations, the structure and
      biological properties of different groups of peptides are presented.

PMID- 17031879
TI  - Lipidated ras and rab peptides and proteins--synthesis, structure, and function.
AB  - Chemical biology can be defined as the study of biological phenomena from a
      chemical approach. Based on the analysis of relevant biological phenomena and
      their structural foundation, unsolved problems are identified and tackled through
      a combination of chemistry and biology. Thus, new synthetic methods and
      strategies are developed and employed for the construction of compounds that are
      used to investigate biological procedures. Solid-phase synthesis has emerged as
      the preferred method for the synthesis of lipidated peptides, which can be
      chemoselectively ligated to proteins of the Ras superfamily. The generated
      peptides and proteins have solved biological questions in the field of the Ras
      superfamily GTPases that are not amendable to chemical or biological techniques
      alone.

PMID- 17031881
TI  - Aromaticity of tri- and tetranuclear metal-carbonyl clusters based on magnetic
      criteria.
AB  - Recently, the sigma-aromaticity model proposed for cyclopropane by Dewar was
      employed to account for the stability of Group 8 trinuclear metal-carbonyl
      compounds [M(3)(CO)(12)] (M=Fe, Ru, Os). This paper further examines this
      hypothesis and provides the first quantitative evidence for the sigma
      aromatic/antiaromatic nature of the [M(3)(CO)(12)]/[M(4)(CO)(16)] species based
      on structural and nucleus-independent chemical-shift analysis. In addition, the
      extent of electron delocalization in tetrahedral [M(4)(CO)(14)] and butterfly
      [M(4)(CO)(15)] is analyzed and compared to prototype cycloalkanes. While
      remarkable analogies exist between metal-carbonyls and cycloalkanes, transition
      metals provide additional overlap possibilities that affect both the ring strain
      and the magnetic properties of metal-carbonyl rings and cages.

PMID- 17031882
TI  - Dihydroimidazophenanthridinium (DIP)-based DNA binding agents with tuneable
      structures and biological activity.
AB  - We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs)
      with large structural diversity (1-29) using a "one-pot" approach. The DNA
      binding constants of DIPs range from 2x10(4) to 1.3x10(5) M(-1), and the free
      energies for binding range from -5.9 to -6.40 kcal mol(-1). Viscosity
      measurements demonstrated that the binding of the compounds caused DNA
      lengthening, thus signifying binding by intercalation. The cytotoxicities of the
      compounds were determined by tetrazolium dye-based microtitration assays and
      showed a large range of values (0.09-11.7 microM). Preliminary molecular
      modelling studies of the DNA-DIP interactions suggested that the DIP moieties can
      interact with DNA by intercalation, and some R groups might facilitate binding by
      minor-groove binding. The results provide insight into how to design biologically
      active DNA binding agents that can interact in these ways.

PMID- 17031883
TI  - Nitric oxide reductase: direct electrochemistry and electrocatalytic activity.

PMID- 17031884
TI  - RNA-templated chemistry in cells: discrimination of Escherichia, Shigella and
      Salmonella bacterial strains with a new two-color FRET strategy.

PMID- 17031885
TI  - Ketoreduction in mycolactone biosynthesis: insight into substrate specificity and
      stereocontrol from studies of discrete ketoreductase domains in vitro.
AB  - Mycolactone, a polyketide toxin responsible for the extensive tissue destruction
      seen in Buruli ulcer, is assembled on a modular polyketide synthase (PKS).
      Despite operating on structurally different intermediates during synthesis, many
      of the ketoreductase (KR) domains of the mycolactone (MLS) PKS have identical
      sequences. This suggests that these enzymes might exhibit an unusually high level
      of substrate promiscuity. However, we show here that when recombinant mycolactone
      KR domains are tested with a range of surrogate substrates, their specificity
      closely matches that of KR domains derived from other PKS systems. In addition,
      our findings reinforce the role of substrate tethering for achieving
      stereochemical control in modular PKSs by affecting the delicate energetics of
      ketoreduction.

PMID- 17031886
TI  - Identification of labile UDP-ketosugars in Helicobacter pylori, Campylobacter
      jejuni and Pseudomonas aeruginosa: key metabolites used to make glycan virulence
      factors.

PMID- 17031887
TI  - Synthesis and characterization of oligodeoxynucleotides containing
      naphthyridine:imidazopyridopyrimidine base pairs at their sticky ends.
      Application as thermally stabilized decoy molecules.
AB  - We describe the synthesis and properties of oligodeoxynucleotides (ODNs)
      containing 1,8-naphthyridine C-nucleoside (Na-NO) and
      imidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside (Im-ON) at the termini. The
      modified ODNs were more resistant (6 to 40 times) than natural DNA to snake venom
      phosphodiesterase (SVPD). Although incorporation of one pair each of Na-NO:Im-ON
      on the sticky ends of the duplex was insufficient for thermal stabilization (+2.5
      degrees C per pair relative to the G:C pair), the duplex containing two
      consecutive Na-NO:Im-ON pairs at its sticky ends was markedly stabilized
      thermally. The stabilizing effect of the incorporation of additional Na-NO:Im-ON
      pairs is estimated to be +7.8 degrees C per pair. Application as thermally
      stabilized decoy molecules to NF-kappaB (p50) was also demonstrated. The DNA
      duplexes containing the Na-NO:Im-ON pairs (ODN I:ODN II and ODN III:ODN IV) acted
      as competitors to the natural NF-kappaB-binding duplex (ODN V: ODN VI), and the
      calculated IC50 values of ODN I:ODN II and ODN III:ODN IV were 20.1+/-13.3 and
      10.9+/-4.8 nM, respectively, greater than that of ODN V:ODN VI.

PMID- 17031888
TI  - Selenolthiol and dithiol C-terminal tetrapeptide motifs for one-step purification
      and labeling of recombinant proteins produced in E. coli.
AB  - We have previously shown that a redox-active selenocysteine-containing
      tetrapeptide-Sel-tag (Gly-Cys-Sec-Gly)-can be used as a C-terminal fusion motif
      for recombinant proteins produced in Escherichia coli. This Sel-tag allows
      selenolate-targeted one-step purification, as well as fluorescent labeling or
      radiolabeling either with gamma emitters (75Se) or with positron-emitting
      radionuclides (11C). Here we have analyzed four different redox-active C-terminal
      motifs, carrying either dithiol (Gly-Cys-Cys-Gly or Ser-Cys-Cys-Ser) or
      selenolthiol (Gly-Cys-Sec-Gly or Ser-Cys-Sec-Ser) motifs. Utilizing these
      different functional motifs with the same recombinant protein (Fel d 1), we were
      able to assess their relative reactivities and potential usefulness for
      biotechnological applications. We found that all four redox-active tags could be
      utilized for efficient one-step purification to provide pure protein from a crude
      bacterial lysate through reversible binding to phenylarsine oxide sepharose, with
      yields and purities comparable to those obtained for a His-tagged protein
      purified by the more common approach with use of a Ni2+ column. For labeling with
      electrophilic fluorescent or radioactive compounds, however, the selenolthiol
      motifs were considerably more efficient than their dithiol counterparts. The
      results thus show that both the selenolthiol- and the dithiol-containing tags can
      serve as efficient alternatives to His-tags for protein purification, while the
      selenolthiol motifs offer additional and unique potential for Sec-targeted
      labeling. It should therefore be possible to utilize these multifunctional
      tetrapeptide motifs to develop a wide range of novel biotechnological
      applications based on Sec targeting with electrophilic compounds.

PMID- 17031889
TI  - Three-step synthesis of sialic acids and derivatives.

PMID- 17031890
TI  - Spontaneous knotting-from oligoamide threads to trefoil knots.

PMID- 17031891
TI  - DNA logic gates based on structural polymorphism of telomere DNA molecules
      responding to chemical input signals.

PMID- 17031892
TI  - Mechanically induced generation of counterions inside surface-grafted charged
      macromolecular films: towards enhanced mechanotransduction in artificial systems.

PMID- 17031893
TI  - Click assembly of 1,2,3-triazole-linked dendrimers, including ferrocenyl
      dendrimers, which sense both oxo anions and metal cations.

PMID- 17031894
TI  - Control of vesicular morphologies through hydrophobic block length.

PMID- 17031895
TI  - Selective binding and easy separation of C70 by nanoscale self-assembled
      capsules.

PMID- 17031896
TI  - Nanostructured thermosensitive polymers with radical scavenging ability.
AB  - The thermosensitive [60]fullerene end-capped poly(N-isopropylacrylamide) was
      successfully synthesized by the reaction of C(60) with dithiobenzoate-terminated
      poly(N-isopropylacrylamide), which was prepared by reversible addition
      fragmentation chain-transfer (RAFT) polymerization in the presence of
      azobisisobutyronitrile (AIBN). Its structure was determined by FTIR, UV/Vis, and
      carbon and proton NMR spectroscopy as well as by size exclusion chromatography
      (SEC). The novel fullerenated polymer retained the thermosensitivity of poly(N
      isopropylacrylamide). Moreover, it is soluble in water and most of the common
      organic solvents. Interestingly, it was able to form nanoparticle clusters in
      methanol and exhibited significant radical scavenging ability in cell viability
      and metabolic activity tests with fibroblasts and NOR-3 radicals.

PMID- 17031897
TI  - A distance geometry heuristic for expanding the range of geometries sampled
      during conformational search.
AB  - A recent study of crystal structures of protein-ligand complexes has shown that
      bioactive conformations tend to be more extended than random ones (Diller and
      Merz, J. Comput. Aid. Mol. Des. 2002, 16, 105-112). Existing conformational
      sampling techniques produce molecular conformations with a distribution of
      geometric sizes that may not cover that of the bioactive conformations. Here, we
      describe a simple heuristic for biasing the conformational search toward more
      extended or compact conformations, while maintaining excellent sampling. The
      method uses a boosting strategy to generate a series of conformations, each of
      which is at least as extended (or compact) as the previous one. We demonstrate
      that this method significantly expands the range of geometric sizes generated
      during the search and thus increases the efficiency of sampling bioactive
      conformations.

PMID- 17031898
TI  - Diatropicity of tetraazanaphthalenes.
AB  - Tetraazanaphthalenes are diatropic molecules, whose magnetic response to a
      magnetic field perpendicular to the molecular plane closely resembles that of
      naphthalene. The out-of-plane component of the magnetic susceptibility tensor and
      its strong anisotropy can be used as quantifiers of magnetic aromaticity. Maps
      showing streamlines and modulus of the current density field provide clear
      evidence for diatropicity of these systems. They also explain the strong
      anisotropy of carbon and nitrogen magnetic shielding, which is determined by the
      big out-of-plane component of the nuclear shielding tensor. The electronic ring
      currents observed in the map deshield the nuclei of ring hydrogens by enforcing
      the local magnetic field and diminishing the out-of-plane component of proton
      shielding.

PMID- 17031899
TI  - Accurate relativistic adapted Gaussian basis sets for Cesium through Radon
      without variational prolapse and to be used with both uniform sphere and Gaussian
      nucleus models.
AB  - Accurate relativistic adapted Gaussian basis sets (RAGBSs) from Cs (Z = 55)
      through Rn (Z = 86) without variational prolapse were developed by using the
      polynomial version of the Generator Coordinate Dirac-Fock method. The RAGBSs
      presented here can be used with any of two popular finite nucleus models, the
      uniform sphere and the Gaussian models. The largest RAGBS error is 4.5 mHartree
      for Radon with a size of 30s27p17d11f.

PMID- 17031900
TI  - Safety concerns cast shadow over novel class of HIV drugs.

PMID- 17031901
TI  - Informal consultation on preventing disability from lymphatic filariasis, WHO,
      Geneva, August 2006.

PMID- 17031902
TI  - Midwife seeks to work for RIPI.

PMID- 17031903
TI  - Recruiting ideas.

PMID- 17031904
TI  - Urine eosinophils method.

PMID- 17031905
TI  - Scandinavian Cardiovascular Journal.

PMID- 17031906
TI  - RTAs and horse ID under the spotlight at this year's BEVA congress.

PMID- 17031907
TI  - Self-reported chronic conditions and EQ-5D index scores in the US adult
      population.
AB  - OBJECTIVE: To examine the unique health-related quality of life (HRQoL)
      decrements associated with common chronic conditions in the general US adult
      population. METHODS: Data were obtained from a study aimed at establishing a US
      population-based set of preference weights for the health states defined by the
      EQ-5D. The EQ-5D is a brief, self-completed instrument for describing and valuing
      HRQoL. As part of that study, along with the EQ-5D items, data regarding socio
      demographic characteristics and chronic medical conditions were collected. The EQ
      5D has five dimensions, from which an index score can be calculated that falls on
      a scale where 0.0 = death and 1.0 = perfect health. Ordinary least squares
      regression models were conducted using the EQ-5D index score as the dependent
      variable to estimate the association between each chronic condition and the index
      score after adjusting for socio-demographic variables. The population sampling
      weights were applied in the analyses to adjust for the over-sampling of the
      minority groups. RESULTS: Approximately three-fifths (62.5%) of the study sample
      reported having at least one of the 18 chronic medical conditions;
      sinusitis(24.8%), hypertension (23.5%), and arthritis (21.5%) were the most
      commonly reported conditions. The chronic conditions that had the greatest
      negative association with EQ-5D index scores were depression and arthritis.
      CONCLUSION: Unique associations were found between several chronic conditions and
      HRQoL after accounting for the presence of other conditions and socio-demographic
      characteristics. The results of this study provide an indication of the relative
      HRQoL decrements associated with various chronic conditions in the general US
      adult population. The major limitation of this analysis is the uncertainty of the
      causal relationship between chronic conditions and HRQoL due to the cross
      sectional nature of the study data. In addition, because it was unknown how well
      the conditions were managed, caution is needed in interpreting study results
      regarding the relative impact of chronic conditions on HRQoL.

PMID- 17031908
TI  - Decisions and revisions.

PMID- 17031909
TI  - Bioethics and health disparity: Adding diversity to the debate.
AB  - BACKGROUND: Advances in biomedical science and technology have raised profound
      challenges to the way we think, feel, and act regarding human practices and
      ideals. Ethicists are needed from diverse populations who can enhance moral
      debate by offering cultural insight as choices are made as to how society should
      approach the expanding medical and biological possibilities. METHODS: In this
      text, we review comments from bioethicists who are focusing on the moral issues
      surrounding health disparity. RESULTS AND CONCLUSIONS: The purpose of the report
      is to ask the reader to begin to understand how to be an informed partner in this
      ethical debate.

PMID- 17031910
TI  - Treatment of prehypertension: how soon is soon enough? What therapy should be
      used?

PMID- 17031911
TI  - [Diarrhea caused by antibiotics].

PMID- 17031912
TI  - Surgical approaches for the management of idiopathic thoracic scoliosis and the
      indications for combined anterior-posterior technique.
AB  - The indications for surgical intervention in patients with idiopathic scoliosis
      have been well defined. The goals of surgery are to achieve fusion and arrest
      progressive curvature while restoring normal coronal and sagittal balance. As
      first introduced by Harrington, posterior fusion, the gold standard of treatment,
      has a proven record of success. More recently, anterior techniques for performing
      fusion procedures via either a thoracotomy or a retroperitoneal approach have
      been popularized in attempts to achieve better correction of curvature, preserve
      motion segments, and avoid some of the complications of posterior fusion such as
      the development of the flat-back syndrome. Anterior instrumentation alone,
      although effective, can be kyphogenic and has been shown to be associated with
      complications such as pseudarthrosis and instrumentation failure. Performing a
      combined approach in patients with scoliosis and other deformities has become an
      increasingly popular procedure to achieve superior correction of deformity and to
      minimize later complications. Indications for a combined approach (usually
      consisting of anterior release, arthrodesis with or without use of
      instrumentation, and posterior segmental fusion) include: prevention of
      crankshaft phenomenon in juvenile or skeletally immature adolescents; correction
      of large curves (75 degrees ) or excessively rigid curves in skeletally mature or
      immature patients; correction of curves with large sagittal-plane deformities
      such as thoracic kyphosis (> 90 degrees ) or thoracic lordosis (> 20 degrees );
      and correction of thoracolumbar curves that need to be fused to the sacrum.
      Surgery may be performed either in a staged proceedure or, more commonly, in a
      single sitting. The authors discuss techniques for combined surgery and
      complication avoidance.

PMID- 17031913
TI  - Coexistence of two different intraspinal tumors. Case report and review of the
      literature.
AB  - The occurrence of multiple neoplasms in the central nervous system is well
      documented. In von Recklinghausen's disease, patients frequently present with
      multiple neurofibromas and/or meningiomas at different sites within the spinal
      axis. However, the presence of multiple, histologically different spinal tumors
      in the absence of von Recklinghausen's disease is extremely rare. The authors
      describe a patient with progressive paraparesis in whom an extradural, malignant
      lesion and a separate benign, intradural tumor of the thoracic spine were found.
      The histological diagnosis of the intradural tumor was a pigmented schwannoma. On
      review of the literature, the authors found nine additional cases of coexisting,
      histologically different tumors of the spine. The majority of these tumors
      occurred in the thoracic spine and, not unexpectedly, intradural meningiomas and
      schwannomas prevailed. Except for the presumed same mesenchymal cell origin of
      neurinomas and meningiomas, no explanation for the coexisting, different spinal
      tumors could be determined.

PMID- 17031914
TI  - Anterior thoracic intradural arachnoid cysts. Case report and review of the
      literature.
AB  - Anterior thoracic intradural arachnoid cysts (ATIACs) are a rare cause of spinal
      cord and nerve root compression, for which different treatment strategies have
      been proposed. Although ATIAC represents a well-known clinical entity, the choice
      of surgical method has not been uniform, and no study has been specifically
      designed to compare the results of the different treatment options adopted. The
      authors report the case of a 40-year old man with a 1-year history of dorsal
      pain, weakness in the lower extremities, gait disturbance, and mild sexual and
      urinary dysfunction. On neurological examination spastic paraparesis, lower
      extremity hypertonia, and hypesthesia below T-2 were demonstrated. Magnetic
      resonance imaging revealed the presence of an ATIAC at the T-2 level. The patient
      underwent complete microsurgical removal of the cyst. The authors conducted a
      Medline search of the relevant literature from 1966 to 1998 and also obtained
      data on other cases in which patients underwent surgical treatment of ATIAC. The
      literature search yielded five such cases. Treatment strategies were complete
      excision and fenestration followed by placement of a shunt. In addition, one case
      was characterized by intraoperative cyst rupture during retraction of the spinal
      cord. Correct preoperative workup coupled with microneurosurgical technique allow
      for successful removal of the lesion and excellent outcome. Based on the
      literature review and the results in our case, the complete excision of ATIAC is
      associated with an excellent outcome, which is different from results achieved
      using other surgical strategies.

PMID- 17031915
TI  - Functional neuronavigation with magnetoencephalography: outcome in 50 patients
      with lesions around the motor cortex.
AB  - The authors conducted a study to evaluate the clinical outcome in 50 patients
      with lesions around the motor cortex who underwent surgery in which functional
      neuronavigation was performed. The sensorimotor cortex was identified in all
      patients with the use of magnetoencephalography (MEG). The MEG-source
      localizations were superimposed onto a three-dimensional magnetic resonance
      image, and the image data set was then implemented into a neuronavigation system.
      Based on this setup, the surgeon chose the best surgical strategy. During
      surgery, the pre- and postcentral gyrus were identified by neuronavigation, and
      in addition, the central sulcus was localized using intraoperative recording of
      somatosensory evoked potentials. In all cases MEG localizations of the sensory or
      motor cortex were correct. In 30% of the patients preoperative paresis improved,
      in 66% no additional deficits occurred, and in only 4% (two patients)
      deterioration of neurological function occurred. In one of these patients the
      deterioration was not related to the method. The method of incorporating
      functional data into neuronavigation systems is a promising tool that can be used
      in more radical surgery to cause less morbidity around eloquent brain areas.

PMID- 17031916
TI  - Surgical treatment for acute spinal cord injury study pilot study #2: evaluation
      of protocol for decompressive surgery within 8 hours of injury.
AB  - Acute spinal cord injury (SCI) is a major public health problem for which there
      is still only limited treatment available. The National Acute Spinal Cord Injury
      Study-2 (NASCIS-2) and -3 clinical trials demonstrated that the use of acute
      pharmacotherapy with methylprednisolone can attenuate the secondary injury
      cascade if administered within 8 hours of acute SCI. However, no trial has been
      performed to examine whether acute surgical decompressive procedures within this
      critical 8-hour time window can improve patients' neurological outcome. The
      purpose of the current prospective Surgical Treatment for Acute Spinal Cord
      Injury Study (STASCIS) pilot study was to determine the feasibility of obtaining
      a radiological diagnosis of spinal canal compromise of 25% or more and to perform
      spinal cord (C3-T1) decompressive procedures by 8 hours postinjury. One of the
      following three decompressive methods was used: 1) traction alone; 2) traction
      and surgery; or 3) surgery alone. Twenty-six patients from eight North American
      centers were entered into the study between 1996 and 1997. Significant
      difficulties were encountered in many centers in performing immediate magnetic
      resonance imaging examination in patients with acute SCI. Fewer than 10% of acute
      cervical SCI patients could be enrolled into this protocol mainly because the
      combination of the required time for rescue, resuscitation, transport, imaging
      study, and surgical preparation exceeded the 8-hour injury-to-decompressive
      surgery window. Eleven patients underwent decompressive procedures initially by
      being placed in traction at a mean time of 10.9 hours postinjury. Those patients
      not undergoing this procedure underwent decompressive surgery at a mean time of
      40.1 hours. However, the surgical decompressive procedure was completed within 12
      hours in seven patients. As a result of these findings, several major changes
      have been made to the STASCIS protocol for early decompressive therapy.

PMID- 17031917
TI  - The fate of the compressed deformed spinal cord after decompressive surgery: MR
      imaging and histopathological findings in experimental studies.
AB  - The authors conducted a study in which they applied the spinal cord compression
      decompression model in rabbits to investigate the morphological changes and
      histopathological findings in the deformed spinal cord over a long-term period
      after performing decompressive surgery. Throughout the experimental period,
      mangnetic resonance (MR) images were obtained frequently; after obtaining a final
      MR image, the spinal cord was dissected and underwent histological examination.
      Immediately after decompressive surgery, axial T1-wieighted MR imaging revealed
      an increase in the cross-sectional area of the spinal cord during the 1st and 2nd
      weeks. The spinal cord area achieved a peak at an average of 5.9 weeks after
      decompressive surgery, when it displayed isointensity on T1- and high-intensity
      on T2-weighted images. The main histological findings were spongy changes in the
      white matter, which persisted for 4 months postsurgery. There was a significant
      correlation between the presurgical spinal cord area and the postsurgical
      decreased number of motor neuron cells. Based on the MR imaging and
      histopathological studies, although the deformed spinal cord that underwent
      compression for 3 months was immediately restored morphologically after
      decompressive surgery, the change in quality in the spinal cord persisted at
      least 4 months.

PMID- 17031918
TI  - Review of clinical trials of neuroprotection in acute spinal cord injury.
AB  - In this paper the authors review the clinical trials of neuroprotection that have
      been performed for the treatment of acute spinal cord injury (SCI). The
      biological rationale for the selection of each treatment modality is discussed
      with reference to current knowledge of the principles in the management of acute
      SCI as well as the primary and secondary injury mechanisms identified by
      experimental and clinical studies of the pathophysiology of acute SCI. The trials
      are evaluated with regard to the availability and use of accurate clinical
      outcome measures, and the methodologies of the trials are critically evaluated
      with an emphasis on prospective randomized controlled studies. A detailed
      description and critical analysis are provided of the results of the 10 clinical
      trials conducted to date in which a randomized prospective controlled design has
      been used. The issue of the therapeutic time window in acute SCI is discussed. To
      date, methylprednisolone is the only effective neuroprotective agent that has
      been established for use in human SCI, and the only therapeutic time window
      established in human SCI is a maximum trauma-to-treatment time of 8 hours.

PMID- 17031919
TI  - A large protonated water cluster H+(H2O)27 in a 3D metal-organic framework.
AB  - A large protonated water cluster, H+(H2O)27, has been trapped and stabilized
      within the well-modulated cavity of a 3D metal-organic framework formed by
      cobalt(II) and 4,4'-bipyridine-N,N'-dioxide with a globular Keggin structure
      [PW12O4]3- anion as template. The structurally characterized protonated water
      cluster might comprise a (H2O)26 shell with Oh symmetry and a monowater core
      within the center which is suggested to be a hydronium ion with the Eigen model.

PMID- 17031920
TI  - A ratiometric CdSe/ZnS nanocrystal pH sensor.
AB  - The development of a reversible chemical sensor based on a CdSe/ZnS nanocrystal
      (NC) is described. Signal transduction is accomplished by fluorescence resonance
      energy transfer (FRET) between the NC and a fluorescent pH-sensitive squaraine
      dye attached to the surface of the NC. The efficiency of FRET, and consequently
      the relative intensity of NC and dye emissions, is modulated with the pH
      dependent absorption cross section of the squaraine dye. The design of a NC
      sensor based on FRET results in a ratiometric sensor since the emission
      intensities of dye and NC may be referenced to the isosbestic point between NC
      and dye emissions. The ratiometric approach allows sensing to be performed,
      regardless of issues surrounding collection efficiency (scattering environment,
      light fluctuations, etc.) and dye:NC loadings.

PMID- 17031921
TI  - Enantioselectivity of redox reaction of DOPA at the gold electrode modified with
      a self-assembled monolayer of homocysteine.
AB  - The enantioselectivity of the self-assembled monolayer (SAM) of homocysteine
      formed on the (111)-oriented gold surface was investigated. We analyzed the redox
      behavior of 3,4-dihydroxyphenylalanine (DOPA), which is an electrochemically
      active chiral molecule, by means of cyclic voltammetry at a gold electrode
      modified with one enantiomeric form of homocysteine. It was demonstrated that the
      homocysteine SAM of one enantiomeric form blocked the redox reaction of only one
      enantiomer of DOPA, with cross inversion for the other enantiomer, in acidic
      solution.

PMID- 17031922
TI  - Aggregation of the amphipathic peptides (AAKA)n into antiparallel beta-sheets.
AB  - Helical wheel projections of peptides based on the repeating unit Ac-(AAKA)n-NH2
      clearly illustrate an amphipathic nature. One should therefore expect these
      peptides to form helices if the number of residues exceeds a certain threshold
      value. Indeed, ECD measurements show that Ac-(AAKA)4-NH2 and, to a minor extent,
      also Ac-(AAKA)3-NH2 exhibit some helical content at millimolar concentrations in
      aqueous solution. Surprisingly, however, these peptides were found to form
      hydrogels with an antiparallel beta-sheet conformation at centimolar
      concentrations. This occurs despite the positively charged lysine side chain
      which would be expected to inhibit the formation of extended beta-sheet layers.

PMID- 17031923
TI  - Determination of enantiomeric excess and concentration of unprotected amino
      acids, amines, amino alcohols, and carboxylic acids by competitive binding assays
      with a chiral scandium complex.
AB  - A practical UV-vis sensing method for enantioselective microanalysis of
      unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous
      solution has been developed. Both concentration and enantiomeric composition of a
      wide range of chiral substrates can be determined with high accuracy by two
      simple competitive binding assays using a scandium complex derived from 1,8-bis(3
      (3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.

PMID- 17031924
TI  - Palladium-catalyzed asymmetric [3 + 2] trimethylenemethane cycloaddition
      reactions.
AB  - Transition-metal-catalyzed trimethylenemethane (TMM) [3 + 2] cycloadditions
      provide direct routes to functionalized cyclopentanes. This reaction has been
      shown to be a highly chemo-, regio-, and diastereoselective process. We report a
      palladium-catalyzed asymmetric [3 + 2] trimethylenemethane (TMM) cycloaddition
      between 3-acetoxy-2-trimethylsilylmethyl-1-propene and various di- and
      trisubstituted olefins. Yields of exo-methylenecyclopentane products range from
      59 to 99%, and enantiomeric excesses range from 58 to 92% ee.

PMID- 17031925
TI  - Gold nanoparticles propulsion from surface fueled by absorption of femtosecond
      laser pulse at their surface plasmon resonance.
AB  - Femtosecond laser irradiation of assembled nanoprisms on a quartz substrate at
      their strong absorbing surface plasmon resonance frequency causes their
      propulsion from the substrate. SEM and AFM show that the particles fly while
      keeping their prismatic shape, but they decrease in size by an amount that can be
      calculated assuming atomic sublimation. Several mechanisms are mentioned, but the
      sublimation mechanism, which rapidly builds up pressure under the particle and
      propels it away from substrate, is discussed in detail. From the kinetic energy
      given to the flying nanoparticle, an initial velocity of approximately 160 m/s (
      approximately 360 miles/h) is calculated. The dependence of the observed flying
      mechanism on the rate of energy deposition (i.e., with nanosecond vs femtosecond
      laser pulses) is discussed.

PMID- 17031926
TI  - At least three contiguous atoms are necessary for CO formation during methanol
      electrooxidation on platinum.
AB  - We have used cyanide-modified Pt(111) electrodes to investigate the size and
      geometry of the minimum atomic ensemble necessary for the oxidation of methanol
      on Pt electrodes. Poison formation on cyanide-modified Pt(111) is completely
      inhibited, the corresponding electrooxidation reaction proceeding, hence,
      exclusively through the reactive intermediate pathway. These results suggest that
      formation of adsorbed CO would require the presence of at least three contiguous
      Pt atoms.

PMID- 17031927
TI  - Infrared line shape of an alpha-carbon deuterium-labeled amino acid.
AB  - The viability of alpha-carbon deuterated bonds (Calpha-D) as infrared (IR) probes
      of protein backbone dynamics was explored through a combination of experiment and
      theory. alpha-Carbon deuterated alanine (Ala-d1) served as a convenient model
      system for a comparison of experiment, density functional theory (DFT), and
      combined quantum mechanical/molecular mechanical (QM/MM) simulations of the
      Calpha-D IR line shape. In addition to the primary Calpha-D absorption, the
      experimental spectrum contains three features that likely result from Fermi
      resonances. DFT calculations supported the assignments and identified the lower
      frequency modes participating in the Fermi resonances. A QM/MM simulation of the
      Ala-d1 line shape was in qualitative agreement with the experiment, including the
      presence of classical analogues of Fermi resonances. These studies demonstrated
      that the Calpha-D line shape is sensitive, via Fermi resonances, to lower
      frequency collective vibrations that are expected to play a role in protein
      dynamics and function, and that the QM/MM approach, which is applicable to
      proteins, is capable of aiding in their interpretation.

PMID- 17031928
TI  - An easy way to sugar-containing polymer vesicles or glycosomes.
AB  - A thioglucose derivative was effectively grafted onto the double bonds of a 1,2
      polybutadiene-block-polystyrene through photoaddition at room temperature. A so
      prepared amphiphilic glycopolymer (17 wt % glucose) could be dispersed in organic
      and in aqueous media, leading to the formation of sugar-containing polymer
      vesicles or "glycosomes".

PMID- 17031929
TI  - Synthesis of single- and double-walled carbon nanotube forests on conducting
      metal foils.
AB  - Here, we report a highly efficient growth of single-walled carbon nanotubes
      (SWNTs) and double-walled carbon nanotubes (DWNTs) on conducting metal foils. We
      found that foils made of Ni-based alloys with Cr or Fe serve as excellent
      substrates for SWNT (DWNT) synthesis. In significant contrast, a CNT grown on Ni,
      Fe foils contains a significant ratio of MWNTs. This result opens up an
      economical route for the mass production of SWNT (DWNT) forests and also enables
      the straightforward integration of CNTs into nanoelectronic devices, such as
      field emission displays.

PMID- 17031930
TI  - Iron-catalyzed [2pi + 2pi] cycloaddition of alpha,omega-dienes: the importance of
      redox-active supporting ligands.
AB  - The bis(imino)pyridine iron bis(dinitrogen) complex, (iPrPDI)Fe(N2)2 (iPrPDI =
      2,6-(2,6-iPr2C6H3NCR)2C5H3N), serves as an efficient precursor for the catalytic
      [2pi + 2pi] cycloaddition of alpha,omega-dienes to yield the corresponding
      bicycles. For amine substrates, the rate of catalytic turnover increases with the
      size of the nitrogen substituents, demonstrating competing heterocycle
      coordination and product inhibition. In one case, a bis(imino)pyridine iron
      azobicycloheptane product was characterized by X-ray diffraction. Preliminary
      mechanistic studies highlight the importance of the redox activity of the
      bis(imino)pyridine ligand to maintain the ferrous oxidation state throughout the
      catalytic cycle.

PMID- 17031931
TI  - Patterned metal nanowire arrays from photolithographically-modified templates.
AB  - An effective procedure for the fabrication of patterned nanowire arrays with
      micron-sized features is presented. Photolithographic methods are utilized to
      form set patterns onto porous anodic alumina membranes (AAM), and these modified
      membranes can then be used in the electrochemical growth of nanowire arrays. This
      approach readily allows the formation of a variety of nanowire array patterns
      with line widths down to several microns.

PMID- 17031932
TI  - Complementary segmental labeling of large RNAs: economic preparation and
      simplified NMR spectra for measurement of more RDCs.
AB  - NMR structure determination of large RNAs is often restricted by limited RDC
      information caused by chemical shift degeneracy. We established a general, time-
      and cost-effective methodology for the preparation of 13C/15N complementary
      labeled RNAs from a single plasmid. Applying this method to the 25 kDa BC1-DTE
      RNA, we were able to resolve severe chemical shift degeneracy, thereby almost
      doubling the number of RDC restraints in comparison to the conventional 13C,15N
      uniform-labeled RNA.

PMID- 17031933
TI  - Pyrones to pyrans: enantioselective radical additions to acyloxy pyrones.
AB  - This paper describes a highly site-, diastereo-, and enantioselective
      intermolecular radical addition/hydrogen atom transfer to hydroxypyrone
      pyromeconic and kojic acids. The methodology can be extended to the formation of
      chiral quaternary centers. The products obtained are densely functionalized pyran
      moieties. The products contain structural features amenable for the introduction
      of additional substituents.

PMID- 17031934
TI  - Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for
      controlled anticancer drug release.
AB  - Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of
      acute promyelocytic leukemia with giving a complete remission rate of 83-95%. ATO
      also shows significant activity in relapsed/refactory multiple myeloma; however,
      efforts to expand clinical utility to other cancers have been limited by its
      toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III)
      materials exhibit a significantly attenuated cytotoxicity that undergoes pH
      triggered release of an active drug. The arsenic drugs are loaded into 100-nm
      scale liposomes at high concentration (>270 mM) and excellent retention (shelf
      life > 6 months at 4 degrees C), as determined by inductively coupled plasma
      optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM),
      and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous
      acid crosses the bilayer membrane in exchange for acetic acid and an insoluble
      transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resultant
      liposomal arsenic nanoparticles appear to be stable in physiological situations
      but release the drug cargo in a lower pH environment, as encountered in
      intracellular endosomes. These drugs exhibit attenuated cytotoxicities against
      human lymphoma tumor cells compared with that of free As2O3. Controlled release
      of arsenic drugs, and hence control of toxicity, is feasible with this system.
      The results demonstrate that cytotoxicity can be controlled via transitions of
      the inorganic drug between solid and solution phases and suggest a mechanism for
      further improvement of the risk/benefit ratio of As2O3 in treatment of a variety
      of cancers.

PMID- 17031935
TI  - Base and phosphate electron detachment energies of deoxyribonucleotide anions.
AB  - Photoelectron spectra of deoxyribonucleotide anions are interpreted with ab
      initio, electron propagator calculations. Ground-state structures display
      hydrogen bonds which are not present in less stable minima that resemble Watson
      Crick fragment geometries. For the adenosine and thymidine anions, there are two
      vertical electron detachment energies (VEDEs) within 0.1 eV of each other that
      correspond to phosphate- and base-centered Dyson orbitals (DOs). The first VEDE
      of the cytidine anion belongs to a phosphate-centered DO. The anomalously low
      VEDE of the guanosine anion is assigned to a base-centered, pi DO. Higher VEDEs
      of all four anions also are assigned.

PMID- 17031936
TI  - The elusive mechanism of olefin metathesis promoted by (NHC)Ru-based catalysts: a
      trade between steric, electronic, and solvent effects.
AB  - The reaction mechanism operative in olefin metathesis has been and still is a
      challenging area of research. Here we contribute to the discussion showing that
      the actual mechanism is a balance of the title effects. In particular, we show
      that the electronic and solvent effects evidenced by experimental studies can be
      easily counterbalanced by steric effects.

PMID- 17031937
TI  - Layered oxysulfides Sr2MnO2Cu2m-0.5Sm+1 (m = 1, 2, and 3) as insertion hosts for
      Li ion batteries.
AB  - The layered oxysulfides Sr2MnO2Cu2m-0.5Sm+1 (m = 1-3) consist of alternating
      perovskite-type Sr2MnO2 layers and copper sulfide layers. The copper ions can be
      replaced electrochemically and reversibly by Li. The lithiated materials were
      studied by Li MAS NMR, and Li resonances were observed with shifts that could be
      rationalized based on the number of sulfide layers. The materials were cycled
      versus Li and showed enhanced capacity retention in comparison to pure Cu2S; the
      good electrochemical performance was ascribed to the presence of the layered
      framework structure and rapid Li+ and Cu+ conductivity in the sulfide layers.

PMID- 17031938
TI  - Site-specific conversion of cysteine thiols into thiocyanate creates an IR probe
      for electric fields in proteins.
AB  - The nitrile stretching mode of the thiocyanate moiety is a nearly ideal probe for
      measuring the local electric field arising from the organized environment of the
      interior of a protein. Nitriles were introduced into three proteins: ribonuclease
      S (RNase S), human aldose reductase (hALR2), and the reaction center (RC) of
      Rhodobacter capsulatus, through a facile synthetic scheme for the transformation
      of cysteine residues into thiocyanatoalanine. Vibrational Stark effect
      spectroscopy and Fourier transform infrared spectroscopy on the modified proteins
      demonstrated that thiocyanate residues are a highly general tool for probing
      electrostatic fields in proteins.

PMID- 17031939
TI  - A biocompatible method of decorporation: bisphosphonate-modified magnetite
      nanoparticles to remove uranyl ions from blood.
AB  - We report on the use of bisphosphonate to functionalize Fe3O4 magnetic
      nanoparticles via dopamine (DA) linkage. Using tetraethyl-3-aminopropane-1,1
      bisphosphonate (BP) as the functional molecule, we created a system with an Fe3O4
      DA-BP nanostructure, which possesses high specificity for removing uranyl ions
      from water or blood. This work demonstrates that magnetic nanoparticles, combined
      with specific receptor-ligand interactions, promise a sensitive and rapid
      platform for the detection, recovery, and decorporation of metal toxins from
      biological environment.

PMID- 17031940
TI  - The open structure of a multi-drug-resistant HIV-1 protease is stabilized by
      crystal packing contacts.
AB  - The introduction of HIV-1 protease (HIV-PR) inhibitors has led to a dramatic
      increase in patient survival; however, these gains are threatened by the
      emergence of multi-drug-resistant strains. Design of inhibitors that overcome
      resistance would be greatly facilitated by deeper insight into the mechanistic
      events associated with binding of substrates and inhibitors, as well as an
      understanding of the effects of resistance mutations on the structure and dynamic
      behavior of HIV-PR. We previously reported a series of simulations that provide a
      model for HIV-PR dynamics, with spontaneous conversions between the bound and
      unbound crystal forms upon addition or removal of an inhibitor. Importantly, the
      unbound protease transiently sampled a third fully open state that permits entry
      to the active site, unlike both crystallographic forms. Recently, a crystal
      structure of unbound HIV-PR was reported for the MDR 769 isolate (PDB: 1TW7);
      unlike all previous experimental structures, the binding pocket is open. It is
      suggested that drug resistance in this strain arises at least in part from the
      inability of inhibitors to induce closing. We carried out simulations of the MDR
      769 HIV-PR mutant and observed that the reported structure is unstable in
      solution and rapidly adopts the semi-open conformation observed for the unbound
      wild-type protease in solution. Further analysis suggests that the wide-open
      structure observed for MDR 769 arises not from sequence variation, but instead is
      an artifact from crystal packing. Thus, despite being the first experimental
      structure to reveal flap opening sufficient for substrate access to the active
      site, this structure may not be directly relevant to studies of inhibitor entry
      or to the cause of HIV-PR drug resistance.

PMID- 17031941
TI  - Dipolar control of monolayer morphology: spontaneous SAM patterning.
AB  - A strategy for controlling relative placements of molecules within multicomponent
      monolayers at the solution-HOPG interface is demonstrated. The monolayers
      assemble from complementary pairs of 1,5-bis-alkyldiether-anthracenes bearing
      self-repelling side chains. Each diether side chain suffers repulsive dipolar
      interactions if it adsorbs next to an identical side chain in the morphology
      normally assumed by 1,5-bis-substituted-anthracene monolayers. Complementary side
      chain pairs experience attractive dipolar interactions when adsorbed as neighbors
      in the normal morphology monolayer. The repulsive and attractive forces
      spontaneously drive formation of a patterned monolayer at the solution-HOPG
      interface. Each molecule adsorbs in its own row, sandwiched between two rows of
      the complementary anthracene. These studies demonstrate the viability of using
      weak dipolar interactions to control molecular placement and monolayer morphology
      and to pattern multicomponent monolayers.

PMID- 17031942
TI  - Unique aggregation of anthrax (Bacillus anthracis) spores by sugar-coated single
      walled carbon nanotubes.
AB  - There has been significant interest in the binding of anthrax spores by molecular
      species, but with only limited success. Proteins and more recently peptides were
      used. However, despite the known presence of carbohydrates on the spore surface,
      carbohydrate-carbohydrate interactions have hardly been explored likely because
      of the lack of required specific platform for synthetic carbohydrates. We report
      the successful use of single-walled carbon nanotubes as a truly unique scaffold
      for displaying multivalent monosaccharide ligands that bind effectively to
      anthrax spores with divalent cation mediation to cause significant spore
      aggregation. The work should have far-reaching implications in development of
      countermeasure technologies.

PMID- 17031943
TI  - Ligand-controlled, complementary stereoselectivity in the platinum-catalyzed
      intramolecular silaboration of alkenes.
AB  - An intramolecular silaboration of borylsilanyl homoallyl ethers was achieved
      using a platinum catalyst, giving 1-oxa-2-silacyclopentanes in high yields. The
      stereoselectivity of the reactions of sec-homoallyl ethers strongly depended on
      the phosphorus ligand of the platinum catalysts used. The platinum complex
      bearing the PCyPh2 ligand was found to be the most trans-selective catalyst
      (trans/cis = 81:19-92:8), whereas a highly cis-selective cyclization was achieved
      using a platinum catalyst having tris(2,4-di-tert-butylphenyl)phosphite ligand
      (trans/cis = 8:92-6:94). The synthetic utility of the intramolecular silaboration
      was demonstrated by the complementary synthesis of a pair of diastereomers of 6
      methylheptane-1,3,5-triol.

PMID- 17031944
TI  - Highly enantioselective transfer hydrogenation of alpha,beta-unsaturated ketones.
AB  - We describe an efficient and highly enantioselective conjugate transfer
      hydrogenation of alpha,beta-unsaturated ketones that is catalyzed by a salt made
      from tert-butyl valinate and a recently introduced powerful chiral phosphoric
      acid catalyst (TRIP).

PMID- 17031945
TI  - Catalytic, enantioselective bifunctional inverse electron demand hetero-Diels
      Alder reactions of ketene enolates and o-benzoquinone diimides.
AB  - In this Communication, we report a system in which an achiral Lewis acid
      (activating the diene) works in concert with a chiral nucleophile (dienophile) to
      effect the first highly enantio- and regioselective catalytic inverse electron
      demand Diels-Alder [4 + 2] cycloaddition reaction to form biologically active
      quinoxalinones from ketene enolates and o-benzoquinone diimides in good to
      excellent yields with >99% ee.

PMID- 17031946
TI  - Multicolor microwave-triggered metal-enhanced chemiluminescence.
AB  - We describe a novel platform technology for both significantly enhancing and
      obtaining chemiluminescence signatures "on-demand", subsequently named Microwave
      Triggered Metal-Enhanced Chemiluminescence. By combining the use of silver
      nanoparticles to plasmon enhance chemiluminescence with the use of low power
      microwaves to localize heating around the nanostructures, we can both optically
      amplify and trigger chemiluminescence reactions. This approach is a significant
      advantage over traditional chemiluminescence techniques and methodologies, such
      as those used for Western Blots, which typically require long periods of time to
      collect chemiluminescence and offer few possibilities of optically amplifying the
      signatures.

PMID- 17031947
TI  - Electrochemical real-time polymerase chain reaction.
AB  - In this work, we report the first electrochemistry-based real-time polymerase
      chain reaction technique for sequence-specific nucleic acid detection. This new
      technique builds upon the advantages of the well-established fluorescence-based
      counterpart, such as short assay time (simultaneous target DNA amplification and
      detection). In addition, this electrochemical approach could employ simple and
      miniaturizable instrumentation compared to the bulky and expensive optics
      required in the fluorescence-based schemes. We have demonstrated a proof-of
      concept experiment showing that the utilization of solid-phase extension of the
      electrode surface-immobilized capture probe with Fc-dUTP during PCR resulted in
      the accumulation of the redox marker on the transducer surface. This new
      technique can be applied to a microfabricated PCR electrochemical device for
      point-of-care diagnostics as well as on-site environmental monitoring and
      biowarfare agent detection.

PMID- 17031948
TI  - The design and investigation of room temperature thermotropic nematic gold
      nanoparticles.
AB  - Nematic gold nanoparticles, covered with a monolayer of calamitic mesogens and
      short hydrocarbon chains, have been synthesized and investigated. The materials
      are chemically stable and exhibit nematic phase behavior at room temperature.

PMID- 17031949
TI  - Organic-organic epitaxy of incommensurate systems: quaterthiophene on potassium
      hydrogen phthalate single crystals.
AB  - Hot-wall epitaxy and molecular-beam epitaxy have been employed for growing
      quaterthiophene thin films on the (010) cleavage face of potassium hydrogen
      phthalate, and the results are compared in terms of film properties and growth
      mode. Even if there is no geometrical match between substrate and overlayer
      lattices, these films are epitaxially oriented. To investigate the physical
      rationale for this strong orientation effect, optical microscopy, atomic force
      microscopy, and X-ray diffraction are employed. A clear correlation between the
      morphology of the thin films and the crystallographic orientation is found. The
      results are also validated by surface potential calculations, which demonstrate
      the primary role played by the corrugation of the substrate surface.

PMID- 17031950
TI  - Thermal denaturing of mutant lysozyme with both the OPLSAA and the CHARMM force
      fields.
AB  - Biomolecular simulations enabled by massively parallel supercomputers such as
      BlueGene/L promise to bridge the gap between the currently accessible simulation
      time scale and the experimental time scale for many important protein folding
      processes. In this study, molecular dynamics simulations were carried out for
      both the wild-type and the mutant hen lysozyme (TRP62GLY) to study the single
      mutation effect on lysozyme stability and misfolding. Our thermal denaturing
      simulations at 400-500 K with both the OPLSAA and the CHARMM force fields show
      that the mutant structure is indeed much less stable than the wild-type, which is
      consistent with the recent urea denaturing experiment (Dobson et al. Science
      2002, 295, 1719-1722; Nature 2003, 424, 783-788). Detailed results also reveal
      that the single mutation TRP62GLY first induces the loss of native contacts in
      the beta-domain region of the lysozyme protein at high temperatures, and then the
      unfolding process spreads into the alpha-domain region through Helix C. Even
      though the OPLSAA force field in general shows a more stable protein structure
      than does the CHARMM force field at high temperatures, the two force fields
      examined here display qualitatively similar results for the misfolding process,
      indicating that the thermal denaturing of the single mutation is robust and
      reproducible with various modern force fields.

PMID- 17031951
TI  - Time-dependent photoluminescence blue shift of the quantum dots in living cells:
      effect of oxidation by singlet oxygen.
AB  - Time-dependent photoluminescence (PL) enhancement, blue shift, and photobleach
      were observed from the thiol-capped CdTe quantum dots (QDs) ingested in mouse
      myoblast cells and human primary liver cancer cells. It was revealed that the PL
      blue shift resulted from the photooxidation of the QD core by singlet oxygen
      molecules formed on the QD core surface.

PMID- 17031952
TI  - Early events in the photochemistry of aryl azides from femtosecond UV/Vis
      spectroscopy and quantum chemical calculations.
AB  - The photochemistry of para- and ortho-biphenylyl azides and 1-naphthyl azide was
      studied by ultrafast spectroscopy. In every case, the singlet azide second
      excited states were observed by transient absorption spectroscopy and were found
      to have lifetimes of hundreds of femtoseconds. The decay of the S(2) states of
      the azides was accompanied by the growth of transient absorption of the
      corresponding singlet nitrenes. The intermediate S(1) state of the azides could
      not be observed due to its low instantaneous concentration resulting from fast
      fragmentation and nitrene formation. Quantum chemical calculations predict that
      the S(2) state of the azide is bound and that there is a much lower barrier
      toward arylnitrene formation from the S(1) state of the azide. Vibrational
      cooling of para-biphenylnitrene (11 ps) was experimentally observed. The lifetime
      of singlet ortho-biphenylnitrene was 16 ps in acetonitrile and was not affected
      by perdeuteration of the aryl ring. The lifetime of singlet 1-naphthylnitrene is
      12 ps in acetonitrile at ambient temperature.

PMID- 17031953
TI  - Dramatic acceleration of olefin epoxidation in fluorinated alcohols: activation
      of hydrogen peroxide by multiple h-bond networks.
AB  - In 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, the epoxidation of
      olefins by hydrogen peroxide is accelerated up to ca. 100 000-fold (relative to
      that in 1,4-dioxane as solvent). The mechanistic basis of this effect was
      investigated kinetically and theoretically. The kinetics of the epoxidation of Z
      cyclooctene provided evidence that higher-order solvent aggregates (rate order in
      HFIP ca. 3) are responsible for the rate acceleration. Activation parameters
      (DeltaS++ = -39 cal/mol.K) indicated a highly ordered transition state in the
      rate-determining step. In line with these findings, DFT simulations revealed a
      pronounced decrease of the activation barrier for oxygen transfer from H(2)O(2)
      to ethene with increasing number of (specifically) coordinated HFIP molecules.
      The oxygen transfer was unambiguously identified as a polar concerted process.
      Simulations (combined DFT and MP2) of the epoxidation of Z-butene were in
      excellent agreement with the experimental data obtained in the epoxidation of Z
      cyclooctene (activation enthalpy, entropy, and kinetic rate order in HFIP of 3),
      supporting the validity of our mechanistic model.

PMID- 17031955
TI  - Why are ionic liquids liquid? A simple explanation based on lattice and solvation
      energies.
AB  - We have developed a simple and quantitative explanation for the relatively low
      melting temperatures of ionic liquids (ILs). The basic concept was to assess the
      Gibbs free energy of fusion (Delta(fus)G) for the process IL(s) --> IL(l), which
      relates to the melting point of the IL. This was done using a suitable Born
      Fajans-Haber cycle that was closed by the lattice (i.e., IL(s) --> IL(g)) Gibbs
      energy and the solvation (i.e., IL(g) --> IL(l)) Gibbs energies of the
      constituent ions in the molten salt. As part of this project we synthesized and
      determined accurate melting points (by DSC) and dielectric constants (by
      dielectric spectroscopy) for 14 ionic liquids based on four common anions and
      nine common cations. Lattice free energies (Delta(latt)G) were estimated using a
      combination of Volume Based Thermodynamics (VBT) and quantum chemical
      calculations. Free energies of solvation (Delta(solv)G) of each ion in the bulk
      molten salt were calculated using the COSMO solvation model and the experimental
      dielectric constants. Under standard ambient conditions (298.15 K and 10(5) Pa)
      Delta(fus)G degrees was found to be negative for all the ILs studied, as expected
      for liquid samples. Thus, these ILs are liquid under standard ambient conditions
      because the liquid state is thermodynamically favorable, due to the large size
      and conformational flexibility of the ions involved, which leads to small lattice
      enthalpies and large entropy changes that favor melting. This model can be used
      to predict the melting temperatures and dielectric constants of ILs with good
      accuracy. A comparison of the predicted vs experimental melting points for nine
      of the ILs (excluding those where no melting transition was observed and two
      outliers that were not well described by the model) gave a standard error of the
      estimate (s(est)) of 8 degrees C. A similar comparison for dielectric constant
      predictions gave s(est) as 2.5 units. Thus, from very little experimental and
      computational data it is possible to predict fundamental properties such as
      melting points and dielectric constants of ionic liquids.

PMID- 17031954
TI  - Targeted acquisition for real-time NMR spectroscopy.
AB  - A target-oriented approach for the acquisition of information in biomolecular NMR
      spectroscopy is being developed. This approach combines concurrent data
      accumulation, processing, and monitoring of spectral quality. Real-time
      estimation of parameters allows acquisition to be stopped when results are
      complete and have a specified precision. The technique is based on
      multidimensional decomposition, which can process incomplete data. An incremental
      nonuniform sampling scheme ensures the optimization of resolution sensitivity. To
      validate this method, 3D HNCO spectra of three biomolecular systems (8 kDa
      ubiquitin, 22 kDa barstar-barnase complex, and 82 kDa malate synthase G) are
      processed incrementally at small acquisition time steps. The range of molecular
      sizes illustrates applicability in both sample- and sensitivity-limited regimes.
      In each case, the target was to acquire all backbone resonances in the spectra.
      For the three systems, the targets are achieved after 4.5 min, 1.6 h, and 22 h of
      acquisition time, respectively. A number of other targets that can be similarly
      monitored as a function of time are discussed.

PMID- 17031956
TI  - Free-energy landscape for beta hairpin folding from combined parallel tempering
      and metadynamics.
AB  - We develop a new free-energy method, based on the combination of parallel
      tempering and metadynamics, and apply this method to the calculation of the free
      energy landscape of the folding beta hairpin in explicit water. We show that the
      combined method greatly improves the performance of both parallel tempering and
      metadynamics. In particular, we are able to sample the high free-energy regions,
      which are not accessible with conventional parallel tempering. We use our results
      to calculate the difference in entropy and enthalpy between the folded and the
      unfolded state and to characterize the most populated configurations in the
      relevant free-energy basins.

PMID- 17031957
TI  - A europium(III) complex as an efficient singlet oxygen luminescence probe.
AB  - A new europium(III) complex, [4'-(10-methyl-9-anthryl)-2,2':6',2"-terpyridine
      6,6"-diyl]bis(methylenenitrilo) tetrakis(acetate)-Eu(3+), was designed and
      synthesized as a highly sensitive and selective time-gated luminescence probe for
      singlet oxygen ((1)O2). The new probe is highly water soluble with a large
      stability constant of approximately 10(21) and a wide pH available range (pH 3
      10), and can specifically react with (1)O2 to form its endoperoxide (EP-MTTA
      Eu(3+)) with a high reaction rate constant at 10(10) M(-1) s(-1), accompanied by
      the remarkable increases of luminescence quantum yield from 0.90% to 13.8% and
      lifetime from 0.80 to 1.29 ms, respectively. The wide applicability of the probe
      was demonstrated by detection of (1)O2 generated from a MoO(4)(2-)/H(2)O2 system,
      a photosensitization system of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin
      tetra(p-toluenesulfonate) (TMPyP), and a horseradish peroxidase catalyzed aerobic
      oxidation system of indole-3-acetic acid (IAA). In addition, it was found that
      the new probe could be easily transferred into living HeLa cells by incubation
      with TMPyP. A time-gated luminescence imaging technique that can fully eliminate
      the short-lived background fluorescence from TMPyP and cell components has been
      successfully developed for monitoring the time-dependent generation of (1)O2 in
      living cells.

PMID- 17031959
TI  - Sorptive reconstruction of CuMCl4 (M = Al and Ga) upon small-molecule binding and
      the competitive binding of CO and ethylene.
AB  - Carbonyl adducts to CuMCl(4) (M = Al and Ga) have been characterized by single
      crystal and/or powder X-ray diffraction, IR and diffuse reflectance UV/vis
      spectroscopy. Up to two equivalents of carbon monoxide ( approximately 200
      cm(3)/g relative to stp) are sorbed at room temperature, with equilibrium binding
      pressures of below 0.5 atm of CO. The carbonyl bonding is shown to be
      nonclassical, implicating the dominance of sigma-bonding and absence of pi-back
      bonding. Analysis of the crystalline structures of the parent and adduct phases
      provides an atomistic picture of the sorptive reconstruction reaction. Comparison
      of the reactivity of CO and ethylene with these CuMCl(4) materials, as well as
      other copper(I) halide compounds that exhibit classical and nonclassical modes of
      bonding, demonstrates the ability to tune the reactivity of the crystalline
      frameworks with selectivity for carbon monoxide or olefins, respectively.

PMID- 17031958
TI  - Proline zwitterion dynamics in solution, glass, and crystalline state.
AB  - Raman and Raman optical activity spectra of L- and D-proline zwitterionic (PROZW)
      forms were recorded for H(2)O and D(2)O solutions in a wide frequency range and
      analyzed with respect to the motion of the proline ring and rotation of the
      carbonyl group. The solution spectra were additionally compared to Raman
      scattering of glass and crystalline powder proline. Solution and glass spectral
      band broadenings are similar and reveal information about the extent of internal
      molecular motion. Two distinct but equally populated flexible forms were found in
      the glass and the solution. The equal population is consistent with NMR data,
      temperature, and concentration dependencies. The molecular flexibility is reduced
      significantly in the crystal, however, where only one conformer is present.
      Consequently, the crystal bands are narrow and exhibit minor frequency shifts.
      The spectra were interpreted with the aid of density functional theory
      computations involving both continuum and explicit solvent. A two-dimensional
      potential energy surface pertaining to the five-member ring puckering coordinates
      was constructed and used for dynamical averaging of spectral properties.
      Comparison of the computed and experimental bandwidths suggests that the
      puckering is strongly correlated with the carbonyl rotation. An averaging over
      these two motions produces similar results. The interpretation of the Raman
      experiments with the aid of the simulation techniques also indicates that the
      environment modulates properties of the hydrophobic part of the molecule
      indirectly by interacting with the ionic group. Such behavior may be important
      for the reactivity and biological activity of proline-containing peptides and
      proteins.

PMID- 17031960
TI  - Sensitivity enhancement of multidimensional NMR experiments by paramagnetic
      relaxation effects.
AB  - One of the main goals of NMR method development is to increase the sensitivity of
      multidimensional NMR experiments or reduce the required acquisition time. In
      these experiments, more than 80% of the NMR instrument time is spent on the
      recycle delay, where the instrument idles to wait for the recovery of proton
      magnetization. In this study, we report a method of using paramagnetic relaxation
      effects to shorten the recycle delays required in multidimensional NMR
      experiments of biological macromolecules. This approach significantly reduces the
      NMR instrument time required. Ni(2+) ion, complexed with the chelating molecule
      DO2A, is used to decrease the proton T(1) relaxation time of biological
      macromolecules without the significant line-broadening effects that are
      associated with most paramagnetic ions. The Ni(DO2A) also significantly decreases
      the T(1) relaxation time of water, thus providing additional sensitivity gain by
      eliminating the saturation of labile amide resonances.

PMID- 17031961
TI  - Characterization of self-assembled monolayers of fullerene derivatives on gold
      surfaces: implications for device evaluations.
AB  - The widely employed approach to self-assembly of fullerene derivatives on gold
      can be complicated due to multilayer formations and head-to-tail assemblies
      resulting from the strong fullerene-fullerene and fullerene-gold interactions.
      These anomalies were not examined in detail in previous studies on fullerene self
      assembled monolayers (SAMs) but were clearly detected in the present work using
      surface characterization techniques including ellipsometry, cyclic voltammetry
      (CV), and X-ray photoelectron spectroscopy (XPS). This is the first time that
      SAMs prepared from fullerene derivatives of thiols/thiol esters/disulfides have
      been analyzed in detail, and the complications due to multilayer formations and
      head-to-tail assemblies were revealed. Specifically, we designed and synthesized
      several fullerene derivatives based on thiols, thiol acetates, and disulfides to
      address the characterization requirements, and these are described and
      delineated. These studies specifically address the need to properly characterize
      and control fullerene-thiol assemblies on gold before evaluating subsequent
      device performances.

PMID- 17031962
TI  - Hydrophobic and ionic interactions in nanosized water droplets.
AB  - A number of situations such as protein folding in confined spaces, lubrication in
      tight spaces, and chemical reactions in confined spaces require an understanding
      of water-mediated interactions. As an illustration of the profound effects of
      confinement on hydrophobic and ionic interactions, we investigate the solvation
      of methane and methane decorated with charges in spherically confined water
      droplets. Free energy profiles for a single methane molecule in droplets, ranging
      in diameter (D) from 1 to 4 nm, show that the droplet surfaces are strongly
      favorable as compared to the interior. From the temperature dependence of the
      free energy in D = 3 nm, we show that this effect is entropically driven. The
      potentials of mean force (PMFs) between two methane molecules show that the
      solvent separated minimum in the bulk is completely absent in confined water,
      independent of the droplet size since the solute particles are primarily
      associated with the droplet surface. The tendency of methanes with charges (M(q+)
      and M(q-) with q(+) = |q(-)| = 0.4e, where e is the electronic charge) to be
      pinned at the surface depends dramatically on the size of the water droplet. When
      D = 4 nm, the ions prefer the interior whereas for D < 4 nm the ions are
      localized at the surface, but with much less tendency than for methanes.
      Increasing the ion charge to e makes the surface strongly unfavorable. Reflecting
      the charge asymmetry of the water molecule, negative ions have a stronger
      preference for the surface compared to positive ions of the same charge
      magnitude. With increasing droplet size, the PMFs between M(q+) and M(q-) show
      decreasing influence of the boundary owing to the reduced tendency for surface
      solvation. We also show that as the solute charge density decreases the surface
      becomes less unfavorable. The implications of our results for the folding of
      proteins in confined spaces are outlined.

PMID- 17031963
TI  - Exchange coupling mediated through-bonds and through-space in conformationally
      constrained polyradical scaffolds: calix[4]arene nitroxide tetraradicals and
      diradical.
AB  - Calix[4]arenes constrained to the 1,3-alternate conformation and functionalized
      at the upper rim with four and two tert-butylnitroxides have been synthesized and
      characterized by X-ray crystallography, magnetic resonance (EPR and (1)H NMR)
      spectroscopy, and magnetic studies. The 1,3-alternate nitroxide tetraradical and
      diradical provide unique polyradical scaffolds for dissection of the through-bond
      and through-space intramolecular exchange couplings. In addition, detailed
      magnetic studies of the previously reported calix[4]arene nitroxide tetraradical,
      which possesses cone conformation in solution, reveal conformational dependence
      of exchange coupling. Through-bond coupling between the adjacent nitroxide
      radicals is mediated by the nitroxide-m-phenylene-CH(2)-m-phenylene-nitroxide
      coupling pathway, and through-space coupling is found between the diagonal
      nitroxide radicals at the conformationally constrained N...N distance of 5-6 A.
      Magnetic studies of the calix[4]arene polyradical scaffolds in frozen solutions
      show that the through-bond exchange coupling in the 1,3-alternate calix[4]arene
      tetraradical is antiferromagnetic, while that in cone calix[4]arene tetraradical
      is ferromagnetic. The through-space exchange couplings are antiferromagnetic in
      both cone and 1,3-alternate calix[4]arene tetraradical, as well as in the 1,3
      alternate calix[4]arene diradical. The exchange coupling constants (|J/k|) are of
      the order of 1 K.

PMID- 17031964
TI  - Residual dipolar couplings in short peptides reveal systematic conformational
      preferences of individual amino acids.
AB  - Residual dipolar couplings (RDCs) observed by NMR in solution under weak
      alignment conditions can monitor average net orientations and order parameters of
      individual bonds. By their simple geometrical dependence, RDCs bear particular
      promise for the quantitative characterization of conformations in partially
      folded or unfolded proteins. We have systematically investigated the influence of
      amino acid substitutions X on the conformation of unfolded model peptides
      EGAAXAASS as monitored by their (1)H(Nu)-(15)N and (1)H(alpha)-(13)C(alpha) RDCs
      detected at natural abundance of (15)N and (13)C in strained polyacrylamide gels.
      In total, 14 single amino acid substitutions were investigated. The RDCs show a
      specific dependence on the substitution X that correlates to steric or
      hydrophobic interactions with adjacent amino acids. In particular, the RDCs for
      the glycine and proline substitutions indicate less or more order, respectively,
      than the other amino acids. The RDCs for aromatic substitutions tryptophane and
      tyrosine give evidence of a kink in the peptide backbone. This effect is also
      observable for orientation by Pf1 phages and corroborated by variations in
      (13)C(alpha) secondary shifts and (3)J(HNH)(alpha) scalar couplings in isotropic
      samples. RDCs for a substitution with the beta-turn sequence KNGE differ from
      single amino acid substitutions. Terminal effects and next neighbor effects could
      be demonstrated by further specific substitutions. The results were compared to
      statistical models of unfolded peptide conformations derived from PDB coil
      subsets, which reproduce overall trends for (1)H(Nu)-(15)N RDCs for most
      substitutions, but deviate more strongly for (1)H(alpha)-(13)C(alpha) RDCs. The
      outlined approach opens the possibility to obtain a systematic experimental
      characterization of the influence of individual amino acid/amino acid
      interactions on orientational preferences in polypeptides.

PMID- 17031965
TI  - Octahedral non-heme oxo and non-oxo Fe(IV) complexes: an experimental/theoretical
      comparison.
AB  - Electron-transfer series are described for three ferric complexes of the
      pentadentate ligand 4,8,11-trimethyl-1,4,8,11-tetraazacyclotetradecane-1-acetate
      (Me(3)cyclam-acetate) with axial chloride, fluoride, and azide ligands. These
      complexes can all be reduced coulometrically to their Fe(II) analogs and oxidized
      reversibly to the corresponding Fe(IV) species. The Fe(II), Fe(III), and Fe(IV)
      species have been studied spectroscopically and their UV-vis, Mossbauer, EPR, and
      IR spectra are presented. The fluoro species [(Me(3)cyclam-acetate)FeF](n+) (n =
      0, 1, 2) have been studied computationally using density functional theory (DFT),
      and the electronic structure of the Fe(IV) dication [(Me(3)cyclam
      acetate)FeF](2+) is compared with that of the isoelectronic Fe(IV) oxo cation
      [(Me(3)cyclam-acetate)FeO](+); the different properties of the two species are
      mainly due to the significantly covalent Fe=O pi bonds in the latter.

PMID- 17031966
TI  - Blood group B galactosyltransferase: insights into substrate binding from NMR
      experiments.
AB  - The biosynthesis of human blood group B antigens is accomplished by a highly
      specific galactosyltransferase (GTB). On the basis of NMR experiments, we propose
      a "molecular tweezers mechanism" that accounts for the exquisite
      stereoselectivity of donor substrate selection. Transferred NOE experiments for
      the first time reveal the bioactive conformation of the donor substrate UDP
      galactose (UDP-Gal) and of its enzymatically inactive analogue, UDP-glucose (UDP
      Glc). Both bind to GTB in a folded conformation that is sparsely populated in
      solution, whereas acceptor ligands bind in a conformation that predominates in
      solution. The bound conformations of UDP-Gal and UDP-Glc are identical within
      experimental error. Therefore, GTB must discriminate between the two activated
      sugars on the basis of a hitherto unknown transition state that can only be
      formed in the case of UDP-Gal. A full relaxation and exchange matrix analysis of
      STD NMR experiments reveals that acceptor substrates dissociate significantly
      faster (k(off) > 100 Hz) from the binding pocket than donor substrates (k(off)
      approximately 10 Hz). STD NMR experiments also directly show that proper
      recognition of the hexopyranose rings of the UDP sugars requires bivalent metal
      cations. At the same time, this analysis furnishes the complete three-dimensional
      structure of the enzyme with its bound donor substrate UDP-Gal on the basis of a
      prior crystal structure analysis. We propose that, upon acceptor binding, GTB
      uses the Asp 302 and Glu 303 side chains as "molecular tweezers" to promote bound
      UDP-Gal but not UDP-Glc into a transition state that leads to product formation.

PMID- 17031967
TI  - Effects of the alternating backbone configuration on the secondary structure and
      self-assembly of beta-peptides.
AB  - Heterochiral homo-oligomers with alternating backbone configurations were
      constructed by using the different enantiomers of the cis- and trans-2
      aminocyclopentanecarboxylic acid (ACPC) monomers. Molecular modeling and the
      spectroscopic techniques (NMR, ECD, and VCD) unequivocally proved that the
      alternating heterochiral cis-ACPC sequences form an H10/12 helix, where extra
      stabilization can be achieved via the cyclic side chains. The ECD and TEM
      measurements, together with molecular modeling, revealed that the alternating
      heterochiral trans-ACPC oligomers tend to attain a polar-strand secondary
      structure in solution, which can self-assemble into nanostructured fibrils. The
      observations indicate that coverage of all the possible secondary structures
      (various helix types and strand-mimicking conformations) can be attained with the
      help of cyclic beta-amino acid diastereomers. A relationship has been established
      between the backbone chirality pattern and the prevailing secondary structure,
      which underlines the role of stereochemical control in the beta-peptide secondary
      structure design and may contribute to future biological applications.

PMID- 17031968
TI  - Solid-state NMR of a paramagnetic DIAD-FeII catalyst: sensitivity, resolution
      enhancement, and structure-based assignments.
AB  - A general protocol for the structural characterization of paramagnetic molecular
      solids using solid-state NMR is provided and illustrated by the characterization
      of a high-spin Fe(II) catalyst precursor. We show how good NMR performance can be
      obtained on a molecular powder sample at natural abundance by using very fast
      (>30 kHz) magic angle spinning (MAS), even though the individual NMR resonances
      have highly anisotropic shifts and very short relaxation times. The results
      include the optimization of broadband heteronuclear (proton-carbon) recoupling
      sequences for polarization transfer; the observation of single or multiple
      quantum correlation spectra between coupled spins as a tool for removing the
      inhomogeneous bulk magnetic susceptibility (BMS) broadening; and the combination
      of NMR experiments and density functional theory calculations, to yield
      assignments.

PMID- 17031969
TI  - Photon gated transport at the glass nanopore electrode.
AB  - The interior surface of the glass nanopore electrode was modified with spiropyran
      moieties to impart photochemical control of molecular transport through the pore
      orifice (15-90 nm radius). In low ionic strength acetonitrile solutions,
      diffusion of a positively charged species (Fe(bpy)(3)(2+)) is electrostatically
      blocked with approximately 100% efficiency by UV light-induced conversion of the
      neutral surface-bound spiropyran to its protonated merocyanine form (MEH+).
      Transport through the pore orifice is restored by either irradiation of the
      electrode with visible light to convert MEH+ back to spiropyran or addition of a
      sufficient quantity of supporting electrolyte to screen the electrostatic field
      associated with MEH+. The transport of neutral redox species through spiropyran
      modified glass nanopores is not affected by light, allowing photoselective
      transport of redox molecules to the electrode surface based on charge
      discrimination. The glass nanopore electrode can also be employed as a
      photochemical trap, by UV light conversion of surface-bound spiropyran to MEH+,
      preventing Fe(bpy)(3)(2+) initially in the pore from diffusing through the
      orifice.

PMID- 17031970
TI  - Energy-resolved photoionization of alkylperoxy radicals and the stability of
      their cations.
AB  - The photoionization of alkylperoxy radicals has been investigated using a newly
      developed experimental apparatus that combines the tunability of the vacuum
      ultraviolet radiation of the Advanced Light Source at Lawrence Berkeley National
      Laboratory with time-resolved mass spectrometry. Methylperoxy (CH(3)OO) and
      ethylperoxy (C(2)H(5)OO) radicals are produced by the reaction of pulsed,
      photolytically produced alkyl radicals with molecular oxygen, and the mass
      spectrum of the reacting mixture is monitored in time by using synchrotron
      photoionization with a double-focusing mass spectrometer. The kinetics of product
      formation is used to confirm the origins and assignments of ionized species. The
      photoionization efficiency curve for CH(3)OO has been measured, and an adiabatic
      ionization energy of (10.33 +/- 0.05) eV was determined with the aid of Franck
      Condon spectral simulations, including ionization to the lowest triplet and
      singlet cation states. Using the appearance energy of CH(3)(+) from CH(3)OO, an
      enthalpy of formation for CH(3)OO of Delta(f) (CH(3)OO) = (22.4 +/- 5) kJ mol(-1)
      is derived. The enthalpy of formation of CH(3)OO(+) is derived as Delta(f) =
      (1019 +/- 7) kJ mol(-1) and the CH(3)(+)-OO bond energy as (CH(3)(+) - O(2)) =
      (80 +/- 7) kJ mol(-1). The C(2)H(5)OO(+) signal is not detectable; however, the
      time profile of the ethyl cation signal suggests its formation from dissociative
      ionization of C(2)H(5)OO. Electronic structure calculations suggest that
      hyperconjugation reduces the stability of the ethylperoxy cation, making the
      C(2)H(5)OO(+) ground state only slightly bound with respect to the ground-state
      products, C(2)H(5)(+) and O(2). The value of the measured appearance energy of
      C(2)H(5)(+) is consistent with dissociative ionization of C(2)H(5)OO via the
      Franck-Condon favored ionization to the a (1)A' state of C(2)H(5)OO(+).

PMID- 17031971
TI  - Assisted desolvation as a key kinetic step for crystal growth.
AB  - The crystallization of materials from a supersaturated solution is a fundamental
      chemical process. Although several very successful models that provide a
      qualitative understanding of the crystal growth process exist, in most cases the
      atomistic detail of crystal growth is not fully understood. In this work,
      molecular dynamics simulations of the morphologically most important surfaces of
      barite in contact with a supersaturated solution have been performed. The
      simulations show that an ordered and tightly bound layer of water molecules is
      present on the crystal surface. The approach of an ion to the surface requires
      desolvation of both the surface and the ion itself leading to an activated
      process that is rate limiting for two-dimensional nucleation to occur. However,
      desolvation on specific surfaces can be assisted by anions adsorbed on the
      crystal surface. This hypothesis, corroborated by crystallization and scanning
      electron microscopy studies, allows the rationalization of the morphology of
      barite crystals grown at different supersaturations.

PMID- 17031972
TI  - Neutral and zwitterionic low-coordinate titanium complexes bearing the terminal
      phosphinidene functionality. Structural, spectroscopic, theoretical, and
      catalytic studies addressing the Ti-P multiple bond.
AB  - Alpha-hydrogen abstraction and alpha-hydrogen migration reactions yield novel
      titanium(IV) complexes bearing terminal phosphinidene ligands. Via an alpha-H
      migration reaction, the phosphinidene ((tBu)nacnac)Ti=P[Trip](CH(2)(tBu)
      ((tBu)nacnac(-) = [Ar]NC((t)Bu)CHC((t)Bu)N[Ar], Ar = 2,6-(CHMe2)(2C6H3, Trip =
      2,4,6-(i)Pr3C6H2) was prepared by the addition of the primary phosphide
      LiPH[Trip] to the nucleophilic alkylidene triflato complex
      ((tBu)nacnac)Ti=CH(t)Bu(OTf), while alpha-H abstraction was promoted by the
      addition of LiPH[Trip] to the dimethyl triflato precursor
      ((tBu)nacnac)Ti(CH)(2)(OTf) to afford ((tBu)nacnac)Ti=P[Trip](CH3). Treatment of
      ((tBu)nacnac)Ti=P[Trip](CH3) with B(C6F5)(3) induces methide abstraction
      concurrent with formation of the first titanium(IV) phosphinidene zwitterion
      complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)}. Complex
      ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5)(3)} [2 + 2] cycloadds readily PhCCPh to afford
      the phosphametallacyclobutene [((tBu)nacnac)Ti(P[Trip]PhCCPh)][CH3B(C6F5)(3)].
      These titanium(IV) phosphinidene complexes possess the shortest Ti=P bonds
      reported, have linear phosphinidene groups, and reveal significantly upfielded
      solution 31P NMR spectroscopic resonances for the phosphinidene phosphorus. Solid
      state 31P NMR spectroscopic data also corroborate with all three complexes
      possessing considerably shielded chemical shifts for the linear and terminal
      phosphinidene functionality. In addition, high-level DFT studies on the
      phosphinidenes suggest the terminal phosphinidene linkage to be stabilized via a
      pseudo Ti[triple bond]P bond. Linearity about the Ti-P-C(ipso) linkage is highly
      dependent on the sterically encumbering substituents protecting the
      phosphinidene. Complex ((tBu)nacnac)Ti=P[Trip]{CH3B(C6F5))(3)} can catalyze the
      hydrophosphination of PhCCPh with H(2)PPh to produce the secondary vinylphosphine
      HP[Ph]PhC=CHPh. In addition, we demonstrate that this zwitterion is a powerful
      phospha-Staudinger reagent and can therefore act as a carboamination precatalyst
      of diphenylacetylene with aldimines.

PMID- 17031973
TI  - Effects of lysine acetylation in a beta-hairpin peptide: comparison of an amide
      pi and a cation-pi interaction.
AB  - The acetylation of lysine is a common posttranslational modification of histone
      proteins, and the interaction of acetylated lysines with aromatic rings is
      commonly observed in transcriptionally relevant protein-protein interactions. To
      determine the nature of this interaction and its potential role in protein
      structure and function, the effect of lysine acetylation on its interaction with
      tryptophan has been investigated within the context of a beta-hairpin peptide.
      Acetylation of Lys results in the replacement of a cation-pi interaction with an
      amide-pi interaction. Despite the loss of positive charge, the interaction energy
      is not significantly perturbed, although the geometry of interaction is
      influenced such that the amide NH interacts directly with the Trp ring.
      Thermodynamic analysis indicates an enthalpic driving force for the
      stabilization, indicating a polar-pi interaction. Acyl lysine analogues formyl
      lysine and trifluoroacetyl lysine were used to further investigate the sterics
      and electronics of the interaction.

PMID- 17031974
TI  - Color fingerprinting of proteins by calixarenes embedded in lipid/polydiacetylene
      vesicles.
AB  - "Naked eye" color detection of proteins was achieved by embedding calixarene
      receptors within vesicles comprising phospholipids and the chromatic polymer
      polydiacetylene. Dramatic visible absorbance changes were induced through
      electrostatic interactions between the protein surface and the vesicle
      incorporated hosts. The colorimetric responses could be induced by micromolar
      protein concentrations, and furthermore, specific protein fingerprints could be
      obtained by incorporating different receptors within the vesicles. Fluorescence
      and circular dichroism experiments confirmed the relationship between the
      colorimetric phenomena and protein docking on the surface of the chromatic
      vesicles. The colorimetric assay constitutes a generic platform for high
      sensitivity detection of soluble proteins and for evaluation of protein surface
      charge distribution.

PMID- 17031975
TI  - Kinetics and mechanism of ketone enolization mediated by magnesium
      bis(hexamethyldisilazide).
AB  - Magnesium bis(hexamethyldisilazide), Mg(HMDS)(2), reacts with substoichiometric
      amounts of propiophenone in toluene solution at ambient temperature to form a
      74:26 mixture of the enolates (E)- and (Z)-[(HMDS)(2)Mg(2)(mu-HMDS){mu
      OC(Ph)=CHCH(3)}], (E)-1 and (Z)-1, which contain a pair of three-coordinate metal
      centers bridged by an amide and an enolate group. The compositions of (E)-1 and
      (Z)-1 were confirmed by solution NMR studies and also by crystallographic
      characterization in the solid state. Rate studies using UV-vis spectroscopy
      reveal the rapid and complete formation of a reaction intermediate, 2, between
      the ketone and magnesium, which undergoes first-order decay with rate constants
      independent of the concentration of excess Mg(HMDS)(2) (DeltaH++ = 17.2 +/- 0.8
      kcal/mol, DeltaS++ = -11 +/- 3 cal/mol.K). The intermediate 2 has been
      characterized by low-temperature (1)H NMR, diffusion-ordered NMR, and IR
      spectroscopy and investigated by computational studies, all of which are
      consistent with the formulation of 2 as a three-coordinate monomer,
      (HMDS)(2)Mg{eta(1)-O=C(Ph)CH(2)CH(3)}. Further support for this structure is
      provided by the synthesis and structural characterization of two model ketone
      complexes, (HMDS)(2)Mg(eta(1)-O=C(t)Bu(2)) (3) and (HMDS)(2)Mg{eta(1)
      O=C((t)Bu)Ph} (4). A large primary deuterium isotope effect (k(H)/k(D) = 18.9 at
      295 K) indicates that proton transfer is the rate-limiting step of the reaction.
      The isotope effect displays a strong temperature dependence, indicative of
      tunneling. In combination, these data support the mechanism of enolization
      proceeding through the single intermediate 2 via intramolecular proton transfer
      from the alpha carbon of the bound ketone to the nitrogen of a bound
      hexamethyldisilazide.

PMID- 17031976
TI  - Thermodynamic and kinetic studies on the binding of nitric oxide to a new enzyme
      mimic of cytochrome p450.
AB  - A new model for the P450 enzyme carrying a SO(3)(-) ligand coordinated to
      iron(III) (complex 2) reversibly binds NO to yield the nitrosyl adduct. The rate
      constant for NO binding to 2 in toluene is of the same order of magnitude as that
      found for the nitrosylation of the native, substrate-bound form of P450(cam) (E.S
      P450(cam)). Large and negative activation entropy and activation volume values
      for the binding of NO to complex 2 support a mechanism that is dominated by bond
      formation with concomitant iron spin change from S = (5)/(2) to S = 0, as
      proposed for the reaction between NO and E.S-P450(cam). In contrast, the
      dissociation of NO from 2(NO) was found to be several orders of magnitude faster
      than the corresponding reaction for the E.S-P450(cam)/NO system. In a
      coordinating solvent such as methanol, the alcohol coordinates to iron(III) of 2
      at the distal position, generating a six-coordinate, high-spin species 5. The
      reaction of NO with 5 in methanol was found to be much slower in comparison to
      the nitrosylation reaction of 2 in toluene. This behavior can be explained in
      terms of a mechanism in which methanol must be displaced during Fe-NO bond
      formation. The thermodynamic and kinetic data for NO binding to the new model
      complexes of P450 (2 and 5) are discussed in reference to earlier results
      obtained for closely related nitrosylation reactions of cytochrome P450(cam) (in
      the presence and in the absence of the substrate) and a thiolate-ligated
      iron(III) model complex.

PMID- 17031977
TI  - Amorphous linear aliphatic polyesters for the facile preparation of tunable
      rapidly degrading elastomeric devices and delivery vectors.
AB  - A versatile method for preparing amorphous degradable elastomers with tunable
      properties that can be easily fabricated into a wide variety of shape-specific
      devices was investigated. Completely amorphous, liquid poly(ester ether)
      prepolymers with number-average molecular weights between 4 and 6 x 10(3) g/mol
      were prepared via condensation polymerization. These liquid prepolymers were then
      thermally cross-linked to form degradable elastomeric structures. The ability to
      vary the composition of these liquid prepolymers allows for easy control of the
      mechanical and degradation properties of the resulting elastomeric structures.
      Materials can be designed to completely degrade in vitro over a range of 30 days
      to 6 months, while the Young's modulus can be varied over 3 orders of magnitude
      (G = 0.02-20 MPa). Also, the liquid nature of these prepolymers makes them
      amenable to a wide variety of fabrication techniques. Using traditional and
      modified imprint lithography techniques, we have fabricated devices that
      demonstrate a wide variety of biologically applicable topologies, which could
      easily be extended to fabricate devices with more complex geometries. Until now,
      no method has combined this ease and speed of fabrication with the ability to
      control the mechanical and degradation properties of the resulting elastomers
      over such a broad range.

PMID- 17031978
TI  - Electronic structure and stability of pentaorganosilicates.
AB  - The exceptional stability of recently reported pentaorganosilicates is
      investigated by bond energy analyses. Experimental coupling constants are used to
      probe their electronic structure, entailing bonds with mixed ionic-covalent
      character. Our analyses reconfirm that the axial bonds are more prone to
      heterolytic cleavage than are the equatorial bonds. Aryl substituents provide
      substantial electronic stabilization by charge delocalization, but cause steric
      crowding due to ortho-hydrogen repulsion. In contrast, silicates with two ax,eq
      biaryl groups are not congested. The remaining substituent is confined to an
      equatorial site, where it is insensitive to elimination. These concepts
      adequately explain the experimentally observed stability trends and are valuable
      for designing other stable pentaorganosilicates.

PMID- 17031982
TI  - Quantum dynamical approach to ultrafast molecular desorption from surfaces.

PMID- 17031983
TI  - Electronic excitations in metals and at metal surfaces.

PMID- 17031984
TI  - Femtochemistry at metal surfaces: nonadiabatic reaction dynamics.

PMID- 17031979
TI  - Racemization in Prins cyclization reactions.
AB  - Isotopic labeling experiments were performed to elucidate a new mechanism for
      racemization in Prins cyclization reactions. The loss in optical activity for
      these reactions was shown to occur by 2-oxonia-Cope rearrangements by way of a
      (Z)-oxocarbenium ion intermediate. Reaction conditions such as solvent,
      temperature, and the nucleophile employed played a critical role in whether an
      erosion in enantiomeric excess was observed. Additionally, certain structural
      features of Prins cyclization precursors were also shown to be important for
      preserving optical purity in these reactions.

PMID- 17031985
TI  - Coherent vibrations of adsorbates induced by femtosecond laser excitation.

PMID- 17031986
TI  - Dynamics of electronic transfer processes at metal/insulator interfaces.

PMID- 17031987
TI  - Photoinduced electron transfer at molecule-metal interfaces.

PMID- 17031988
TI  - Photochemistry on metal nanoparticles.

PMID- 17031989
TI  - Patterned atomic reaction at surfaces.

PMID- 17031990
TI  - Electronic control of single-molecule dynamics.

PMID- 17031991
TI  - Photoreaction dynamics of molecular adsorbates on semiconductor and oxide
      surfaces.

PMID- 17031992
TI  - Solvated electrons on metal oxide surfaces.

PMID- 17031993
TI  - Surface science studies of the photoactivation of TiO2--new photochemical
      processes.

PMID- 17031994
TI  - Confirmation of peanut protein using peptide markers in dark chocolate using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - Detection of peptides from the peanut allergen Ara h 1 by liquid chromatography
      mass spectrometry (LC-MS) was used to identify and estimate total peanut protein
      levels in dark chocolate. A comparison of enzymatic digestion subsequent to and
      following extraction of Ara h 1 from the food matrix revealed better limits of
      detection (LOD) for the pre-extraction digestion (20 ppm) than for the
      postextraction digestion (50 ppm). Evaluation of LC-MS instruments and scan modes
      showed the LOD could be further reduced to 10 ppm via a triple-quadrupole and
      multiple-reaction monitoring. Improvements in extraction techniques combined with
      an increase in the amount of chocolate extracted (1 g) improved the LOD to 2 ppm
      of peanut protein. This method provides an unambiguous means of confirming the
      presence of the peanut protein in foods using peptide markers from a major
      allergen, Ara h 1, and can easily be modified to detect other food allergens.

PMID- 17031995
TI  - Electrochemical estimation of the polyphenol index in wines using a laccase
      biosensor.
AB  - The use of a laccase biosensor, under both batch and flow injection (FI)
      conditions, for a rapid and reliable amperometric estimation of the total content
      of polyphenolic compounds in wines is reported. The enzyme was immobilized by
      cross-linking with glutaraldehyde onto a glassy carbon electrode. Caffeic acid
      and gallic acid were selected as standard compounds to carry out such estimation.
      Experimental variables such as the enzyme loading, the applied potential, and the
      pH value were optimized, and different aspects regarding the operational
      stability of the laccase biosensor were evaluated. Using batch amperometry at 
      200 mV, the detection limits obtained were 2.6 x 10(-3) and 7.2 x 10(-4) mg L(-1)
      gallic acid and caffeic acid, respectively, which compares advantageously with
      previous biosensor designs. An extremely simple sample treatment consisting only
      of an appropriate dilution of wine sample with the supporting electrolyte
      solution (0.1 mol L(-1) citrate buffer of pH 5.0) was needed for the amperometric
      analysis of red, rose, and white wines. Good correlations were found when the
      polyphenol indices obtained with the biosensor (in both the batch and FI modes)
      for different wine samples were plotted versus the results achieved with the
      classic Folin-Ciocalteu method. Application of the calibration transfer
      chemometric model (multiplicative fitting) allowed that the confidence intervals
      (for a significance level of 0.05) for the slope and intercept values of the
      amperometric index versus Folin-Ciocalteu index plots (r = 0.997) included the
      unit and zero values, respectively. This indicates that the laccase biosensor can
      be successfully used for the estimation of the polyphenol index in wines when
      compared with the Folin-Ciocalteu reference method.

PMID- 17031996
TI  - Determination of trace hydroxyl radicals by flow injection spectrofluorometry and
      its analytical application.
AB  - On the basis of the fluorescence increase of the reaction of ninhydrin with
      hydroxyl radicals, a new method for the determination of trace amounts of
      hydroxyl radicals by flow injection spectrofluorometry is presented. The
      introduction of flow injection analysis brought better reproducibility and
      avoided the effect of oxygen and other substances in the environment on the
      reaction of ninhydrin with hydroxyl radicals. Under optimum experimental
      conditions, the hydroxylated product of ninhydrin had excitation and emission
      maxima at 300 and 406 nm, respectively. The linear range was 2.60 x 10(-7) to
      4.00 x 10(-5) M, and the limit of detection was 7.91 x 10(-8) M. A high analysis
      rate of 22 samples per hour was obtained. The proposed method has been applied
      successfully to the determination of scavenging effects of thiourea and vitamin C
      on hydroxyl radicals as well as to the evaluation of antioxidant capacities of
      some natural food.

PMID- 17031997
TI  - Evaluation of post-polymerase chain reaction melting temperature analysis for
      meat species identification in mixed DNA samples.
AB  - Real-time uniplex and duplex polymerase chain reaction (PCR) assays with a SYBR
      Green I post-PCR melting curve analysis were evaluated for the identification and
      quantification of bovine, porcine, horse, and wallaroo DNA in food products.
      Quantitative values were derived from threshold-cycle (C(t)) data obtained from
      serial dilutions of purified DNA. The limits of detection in uniplex reactions
      were 0.04 pg for porcine and wallaroo DNA and 0.4 pg for cattle and horse DNA.
      Species specificity of the PCR products was tested by the identification of peaks
      in DNA melting curves, measured as the decrease of SYBR Green I fluorescence at
      the dissociation temperature. The peaks could be distinguished above the
      background even at the lowest amount of template DNA detected by the C(t) method.
      The system was also tested in duplex reactions, by use of either single-species
      DNA or DNA admixtures containing different shares of two species. The minimum
      proportions of each DNA species allowing the resolution of T(m) peaks in the
      duplex reactions were 5% (cattle or wallaroo) in cattle/wallaroo mixtures, 5%
      porcine and 1% horse in porcine/horse mixtures, 60% porcine and 1% wallaroo in
      porcine/wallaroo mixtures, and 1% cattle and 5% horse in cattle/horse mixtures. A
      loss in the sensitivity of the method was observed for some DNA combinations in
      the duplex assay. In contrast, the results obtained from SYBR Green I uniplex and
      duplex reactions with single-species DNA were largely comparable to those
      obtained previously with species-specific TaqMan probes, showing the suitability
      of that simpler experimental approach for large-scale analytical applications.

PMID- 17031998
TI  - Electromigration profiles of Cynomorium songaricum based on capillary
      electrophoresis with amperometric detection.
AB  - A high-performance capillary electrophoresis with amperometric detection (CE-AD)
      method has been developed for the simultaneous determination of the
      pharmacologically active ingredients in Cynomorium songaricum in this work. Under
      the optimum conditions, phloridzin, epicatechin, catechin, naringenin, rutin,
      luteolin, quercetin, gallic acid, and protocatechuic acid can be well separated
      or nearly baseline separated (epicatechin and catechin peaks) within 31 min at
      the separation voltage of 14 kV in a 50 mmol L(-1) Borax running buffer (pH 9.0).
      Detection limits (S/N=3) ranged from 5.7 x 10(-8) to 8.5 x 10(-9) g mL(-1) for
      all nine analytes. This procedure was successfully used for the analysis and
      comparison of the content difference of C. songaricum samples collected from
      different places based on their electrophorograms or "electromigration profiles".

PMID- 17031999
TI  - Rapid quantification of the phenolic fraction of Spanish virgin olive oils by
      capillary electrophoresis with UV detection.
AB  - A rapid and reliable capillary zone electrophoresis method was used as a tool to
      obtain both qualitative and quantitative information about simple phenols,
      lignans, complex phenols (isomeric forms of secoiridoids), phenolic acids, and
      flavonoids in the solid-phase separation extracts from different Spanish extra
      virgin olive oil in a short time (less than 6 min). Peak identification was done
      by using commercial and HPLC-isolated standards, studying the information of the
      electropherograms obtained at several wavelengths and also using the information
      previously reported. For the quantification of lignans and complex phenols
      (secoiridoid derivatives), we used a reference compound (oleuropein glucoside) at
      two different wavelengths (200 and 240 nm) and for the quantification of tyrosol
      and flavonoids, we used their commercially available standards.

PMID- 17032000
TI  - Evaluation of analytical methods for carotenoid extraction from biofortified
      maize (Zea mays sp.).
AB  - Biofortification of maize with beta-carotene has the potential to improve vitamin
      A status in vitamin A deficient populations where maize is a staple crop.
      Accurate assessment of provitamin A carotenoids in maize must be performed to
      direct breeding efforts. The objective was to evaluate carotenoid extraction
      methods and determine essential steps for use in countries growing biofortified
      maize. The most reproducible method based on coefficient of variation and
      extraction efficiency was a modification of Kurilich and Juvik (1999). Heat and
      saponification are required to release carotenoids from biofortified maize and
      remove oils interfering with chromatographic analysis. For maize samples with
      high oil content, additional base may be added to ensure complete saponification
      without compromising results. Degradation of internal standard before carotenoids
      were released from the maize matrix required the addition of internal standard
      after heating to prevent overestimation of carotenoids. This modified method
      works well for lutein, zeaxanthin, beta-cryptoxanthin, alpha-carotene, and beta
      carotene.

PMID- 17032001
TI  - Spinach cultigen variation for tissue carotenoid concentrations influences human
      serum carotenoid levels and macular pigment optical density following a 12-week
      dietary intervention.
AB  - Increasing intakes of carotenoid-rich plant foods can increase serum carotenoid
      concentrations and macular pigment optical density (MPOD) in most, but not all,
      individuals. Research objectives for this study were to (1) characterize tissue
      lutein (L) and beta-carotene (BC) concentrations in carotenoid-rich spinach
      (Spinacia oleracea L.) cultigens and (2) determine serum carotenoid and MPOD
      responses in human subjects consuming spinach cultigens differing in tissue L and
      BC concentrations. Thirteen spinach cultigens were evaluated for carotenoid
      accumulations over two consecutive growing seasons. "Springer" (8.4 and 6.5
      mg/100 g of fresh mass for L and BC, respectively) and "Spinner" (12.1 and 9.2
      mg/100 g of fresh mass for L and BC, respectively) spinach cultigens were
      selected for a dietary intervention study and represented low- and high-L
      concentrations. The high-L ("Spinner") and low-L ("Springer" ) spinach treatment
      groups consisted of 10 subject volunteers ingesting five 50-g spinach
      servings/week during a 12-week intervention. Average serum L concentrations
      increased by 22% (P = 0.07) from baseline (0.233 micromol/L) to 12 weeks (0.297
      micromol/L) for subjects consuming low-L spinach. Subjects consuming high-L
      spinach showed increases of 33% (P = 0.04) in serum L from baseline (0.202
      micromol/L) to 12 weeks (0.300 micromol/L). Average MPOD did not change for the
      low-L treatment group; however, subjects in the high-L group demonstrated
      increases (P = 0.02) in MPOD at the 30' eccentricity between baseline (0.343) and
      12 weeks (0.374). This study demonstrates that serum carotenoid and MPOD are
      determined by L concentrations present in the spinach matrix. Results emphasize
      the role of cultigen selection among vegetable crops in determining phytochemical
      effects on human health.

PMID- 17032002
TI  - Bioavailability of genistein and its glycoside genistin as measured in the portal
      vein of freely moving unanesthetized rats.
AB  - The present study describes an in vivo bioavailability experiment for genistein
      and its glycoside genistin, either as pure compounds or from a soy protein
      isolate extract, using freely moving unanesthetized rats with a cannulation in
      the portal vein. The results show that genistein is readily bioavailable, being
      observed in portal vein plasma at the first point of detection at 15 min after
      dosing. The AUC(0-24h) values for total genistein and its conjugates were 54, 24,
      and 13 microM h for genistein, genistin, and an enriched protein soy extract,
      respectively. These results indicate that the bioavailability of genistein is
      higher for the aglycon than for its glycoside. Genistin is partly absorbed in its
      glycosidic form. It is concluded that bioavailability studies based on portal
      vein plasma levels contribute to insight into the role of the intestine and liver
      in deglycosylation and uptake characteristics of glycosylated flavonoids.

PMID- 17032003
TI  - Bovine beta-casein (1-28), a casein phosphopeptide, enhances proliferation and IL
      6 expression of mouse CD19+ cells via Toll-like receptor 4.
AB  - This study was conducted to elucidate the target cells and receptors which
      participate in the mitogenic and interleukin (IL)-6-enhancing effect of bovine
      beta-casein (1-28), a casein phosphopeptide. When the spleen lymphocyte subset
      (CD4+, CD8+, and CD19+ cells) from C3H/HeN mice was cultured with the beta-casein
      (1-28), it exerted a dose-dependent mitogenic effect on CD19+ cells. The effect
      of beta-casein (1-28) was not apparent in the case of CD19+ cells from C3H/HeJ
      mouse. In addition, the effect was significantly inhibited by treating the
      C3H/HeN mouse-derived CD19+ cells with neutralizing antibody for toll-like
      receptor 4 (TLR4). Reverse transcription-polymerase chain reaction analysis
      showed that the beta-casein (1-28) exerted an IL-6-enhancing effect on the CD19+
      cells. The effect was also abrogated in either C3H/HeJ mouse-derived CD19+ cell
      culture or the anti-TLR4 antibody-added culture. These results suggest that the
      beta-casein (1-28) stimulates both proliferation and IL-6 expression of CD19+
      cells via TLR4.

PMID- 17032004
TI  - Oxidant/antioxidant properties of Croatian native propolis.
AB  - Native propolis was defined as propolis powder collected from the continental
      part of Croatia and prepared according to a patented process that preserves all
      the propolis natural nutritional and organoleptic qualities. Nine phenolic
      compounds (out of thirteen tested) in propolis sample were detected by high
      performance liquid chromatography (HPLC) analysis. Among them chrysin was the
      most abundant (2478.5 microg/g propolis). Contrary to moderate antioxidant
      activity of propolis examined in vitro (ferric reduction antioxidant power; FRAP
      assay), propolis as a food supplement modulated antioxidant enzymes (AOE) and
      significantly decreased lipid peroxidation processes (LPO) in plasma, liver,
      lungs, and brain of mice. The effect was dose- and tissue-dependent. The lower
      dose (100 mg/kg bw) protected plasma from oxidation, whereas the higher dose (300
      mg/kg bw) was pro-oxidative. Hyperoxia (long-term normobaric 100% oxygen)
      increased LPO in all three organs tested. The highest vulnerability to oxidative
      stress was observed in lungs where hyperoxia was not associated with augmentation
      of AOE. Propolis protected lungs from hyperoxia by increased catalase (CAT)
      activity. This is of special importance for lungs since lungs of adult animals
      are highly vulnerable to oxidative stress because of their inability to augment
      AOE activity. Because of its strong antioxidant and scavenging abilities, native
      propolis might be used as a strong plant-based antioxidant effective not only in
      physiological conditions but also in cases that require prolonged high
      concentration of oxygen.

PMID- 17032005
TI  - Influence of soy aglycon isoflavones on bone-related traits and lens protein
      characteristics of ovariectomized rats and bioactivity performance of
      osteoprogenitor cells.
AB  - Health benefits of soy isoflavones have attracted the concern of the public and
      the interest of health-care professionals. In this study, two trials were
      conducted in characterizing bone-related traits and lens proteins as affected by
      supplementation of soy aglycon isoflavones (SAI). In trial 1, an in vivo study,
      20 Sprague-Dawley rats were ovariectomized (OVX) and randomly distributed into
      OVX and OVX+SAI (135 mg of SAI/kg of feed; 8.33 mg/kg body weight; 2.5 mg/day)
      groups. Another group containing 10 rats with a sham operation was control
      (Sham). The experiment period was 3 months, and the rats were subjected to bone
      related traits and lens protein characterization. In trial 2, an in vitro study,
      osteoprogenitor cells (UMR-106) were divided into SAI-supplemented (0.5 mg of
      SAI/mL of medium) and unsupplemented groups. Results of the in vivo study
      indicated that daily BW gains in the OVX and OVX+SAI groups were greater than
      that of the Sham group (p < 0.05). Bone ash and Ca contents of the Sham and
      OVX+SAI groups were higher than those of the OVX group (p < 0.05), while bone
      density, strength, and phosphorus contents among groups varied insignificantly (p
      > 0.05). When the lens proteins were extracted and analyzed with size-exclusion
      HPLC, the contents of beta- and gamma-crystallins were lowest in the OVX group
      and the protein solubility decrease could be recovered by dietary SAI
      supplementation (shown by OVX+SAI group). Based on Raman spectra of the isolated
      lens proteins, disulfide bonds were observed more in OVX lens than in the Sham
      and OVX+SAI lens. Results of in vitro study with osteoprogenitor cells revealed
      that cell viability, alkaline phosphatase activity, osteocalcin, and Ca contents
      of the SAI-supplemented group were higher than those of the unsupplemented group
      (p < 0.05). The likely potency to enhance bone and lens health by SAI
      supplementation is worth pointing out.

PMID- 17032006
TI  - Polyphenolic profiles and antioxidant activities of heartnut (Juglans
      ailanthifolia Var. cordiformis) and Persian walnut (Juglans regia L.).
AB  - The polyphenolic compositions of three heartnut (Juglans ailanthifolia var.
      cordiformis) varieties (Imshu, Campbell CW1, and Campbell CW3) were examined and
      compared with those of two Persian walnut (Juglans regia L.) varieties (Combe and
      Lake). The nuts were defatted, extracted, and separated into three different
      fractions, the free phenolic acid (FPA), acid-hydrolyzable phenolic acid (AHPA),
      and bound phenolic acid (BPA) fractions. The total phenolic contents (TPCs) in
      both FPA and AHPA of the Persian walnuts were significantly higher (P < 0.001)
      than those of the heartnuts, but not in the BPA (P = 0.20). LC-ESI-MS(n)()
      studies revealed that except for the FPA fraction, the major polyphenolics in
      both heartnut and Persian walnut were ellagic acid and valoneic acid dilactone.
      Persian walnuts contained an average of 0.29 and 1.31 mg of ellagic acid/g nut in
      the 80% methanol extractable fractions FPA and AHPA, respectively. Heartnuts
      contained an average of 0.16 and 0.60 mg of ellagic acid/g nut in the respective
      fractions. Bound ellagic acid in the residue was 0.93 and 0.70 mg/g of nut in the
      Persian walnut and in the heartnut, respectively. Valoneic acid dilactone was
      tentatively identified and quantified as milligrams of ellagic acid equivalent
      per gram of nut. These components were found to contribute to the strong total
      antioxidant activities measured using ferric reducing antioxidant power and
      photochemiluminescence methods.

PMID- 17032007
TI  - Production and characterization of human extracellular superoxide dismutase in
      the methylotrophic yeast Pichia pastoris.
AB  - Reactive oxygen species are associated with various diseases including
      cardiovascular diseases, neurological disorders, and pulmonary diseases.
      Extracellular superoxide dismutase (ECSOD) is an antioxidant enzyme secreted by
      cells to prevent overproduction of reactive oxygen species. We expressed an ECSOD
      gene isolated from a human aortic smooth muscle cDNA library in the
      methylotrophic yeast Pichia pastoris. A synthetic secretion cassette was
      constructed with the inducible promoter of the alcohol oxidase 1 gene (AOX1) and
      the yeast alpha-mating factor signal peptide. As much as 25% of the total protein
      was ECSOD in some transformants grown under inducing conditions. After 36 h of
      methanol induction, ECSOD was exported into the culture medium at a concentration
      of approximately 440 mg/L with an antioxidative activity of 760 +/- 20 U/mg
      ECSOD. Transformed yeast cells were more resistant to heat shock and H(2)O(2)
      oxidative stress, indicating that the human ECSOD expressed by P. pastoris had
      multiple biological functions. Our data suggest that the methylotrophic yeast
      inducible system is suitable for large-scale production of enzymatically active
      human ECSOD.

PMID- 17032008
TI  - Optimization of the extraction of antioxidative constituents of six barley
      cultivars and their antioxidant properties.
AB  - Response surface methodology (RSM) was used to predict the optimum conditions of
      extraction of barley samples (organic solvent percent in the extraction medium,
      temperature, and time). Antioxidant capacity in the barley meals was highest
      under optimum extraction conditions of 80.2% methanol and 60.5 degrees C for
      38.36 min as predicted by RSM. Phenolic antioxidative compounds of six barley
      cultivars, namely, Falcon, AC Metcalfe, Tercel, Tyto, Phoenix, and Peregrine,
      were extracted under the conditions obtained by RSM after defatting with hexane,
      and subsequently the extracts were assessed for their antioxidant and antiradical
      activities and metal chelation efficacy. The potential of barley extracts in
      inhibiting peroxyl and hydroxyl radical induced supercoiled DNA double-strand
      scission was also studied. Total phenolic content as measured according to Folin
      Ciocalteu's method ranged from 13.58 to 22.93 mg of ferulic acid equiv/g of
      defatted material, with the highest content in Peregrine. Total antioxidant
      activity as measured by Trolox equivalent antioxidant capacity ranged from 3.74
      to 6.82 micromol/g of defatted material. Metal chelation capacity of the extracts
      as measured by 2,2'-bipyridyl competition assay varied from 1.1 to 2.1 micromol
      of ethylenediaminetetraacetic acid equiv/g of defatted material. IC(50) values
      for 1,1-diphenyl-2-picrylhydrazyl radical as measured by electron paramagnetic
      resonance ranged from 1.51 to 3.33 mg/mL, whereas the corresponding values for
      hydroxyl radical ranged between 2.20 and 9.65 mg/mL. Inhibition of peroxyl
      radical induced supercoiled DNA scission ranged from 78.2 to 92.1% at the
      concentration of 4 mg/mL of extracts, whereas the corresponding values for
      hydroxyl radical induced DNA scission ranged from 53.1 to 65.3%.

PMID- 17032009
TI  - Free radical scavenging effect of Pu-erh tea extracts and their protective effect
      on oxidative damage in human fibroblast cells.
AB  - In the present study, we successively extracted the Pu-erh tea with acetone,
      water, chloroform, ethyl acetate, and n-butanol, and the extracts were then
      isolated by column chromatography. Our study demonstrates that the Pu-erh tea
      ethyl acetate extract, n-butanol extract, and their fractions had superoxide
      anion and hydroxyl radical scavenging activity: fractions 2 and 8 from the ethyl
      acetate extract and fractions 2, 4, and 5 from the n-butanol extract showed
      protective effects against hydrogen peroxide-induced damage in human fibroblast
      HPF-1 cells and increased the cells' viability under normal cell culture
      conditions. In addition, it is found that these fractions, except fraction 5 from
      the n-butanol extract, decreased the accumulation of intracellular reactive
      oxygen species in hydrogen peroxide-induced HPF-1 cells. Interestingly, the
      antioxidant effect of fraction 8 from the ethyl acetate extract on the above four
      systems was much stronger than that of the typical green tea catechin (-)
      epigallocatechin-3-gallate, but there were almost no monomeric polyphenols,
      theaflavins, and gallic acid in fraction 8.

PMID- 17032010
TI  - Secoisolariciresinol and matairesinol of sea buckthorn (Hippophae rhamnoides L.)
      berries of different subspecies and harvesting times.
AB  - Sea buckthorn (Hippophae rhamnoides) seeds, berries, and berry fractions are
      often used as sources of bioactive ingredients for health products. The aim of
      the present study was to analyze lignans in these fractions of sea buckthorn.
      Secoisolariciresinol and matairesinol in seeds, fruit pulp/peel, and whole
      berries of sea buckthorn of three subspecies were analyzed by isotope dilution
      gas chromatography-mass spectrometry. The total content of the two lignans
      secoisolariciresinol and matairesinol varied widely from 8 to 139 microg/100 g in
      fresh berries and from 51 to 319 microg/100 g in dry berries. The content of
      secoisolariciresinol varied in the range of 34-313 microg/100 g of dry mass in
      the fruit pulp/peel and 93-355 microg/100 g in dry seeds. The content of
      matairesinol fell within the range of 3-25 microg/100 g in dry pulp/peel and 1-13
      microg/kg in dry seeds. Wild H. rhamnoides ssp. sinensis contained a
      significantly higher total level of secoisolariciresinol and matairesinol in dry
      seeds, dry berries, and fresh berries compared with wild ssp. rhamnoides (253 vs
      135 microg/100 g, P < 0.01, in seeds; 224 vs 153 microg/100 g, P < 0.05, in dry
      berries; 71 vs 29 g/100 g, P < 0.01, in fresh berries) and the cultivar of ssp.
      mongolica (253 vs 112 microg/100 g in seeds, 71 vs 9 microg/100 g in fresh
      berries). Harvesting dates had a significant influence on the content of the two
      lignans in seeds, fruit pulp/peel, and whole berries. This is the first report of
      lignans in sea buckthorn.

PMID- 17032011
TI  - Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic
      agent in an animal model, and a significant contributor to antioxidants in the
      European and American Diets.
AB  - Chocolate today is often viewed as a food or snack with little nutritional value.
      The high saturated fat content of chocolate has also contributed to the belief
      that its consumption increases the risk of heart disease. However, recent human
      studies have proven that chocolate has beneficial effects on some pathogenic
      mechanisms of heart disease such as endothelial function and blood pressure.
      Although the antioxidant properties of chocolate have been known for some time,
      there has been no examination of its place in the U.S. diet as a source of
      antioxidants. This paper demonstrates that chocolate makes a significant
      contribution to U.S. per capita dietary antioxidants and by inference the
      European Community's. In the U.S. diet chocolate is the third highest daily per
      capita antioxidant source. An ex vivo study shows that epicatechin, a major
      polyphenol in chocolate and chocolate extracts, is a powerful inhibitor of plasma
      lipid oxidation due to polyphenols' ability to bind to lower density
      lipoproteins. Conversely, the fat from chocolate alone is a pro-oxidant in this
      model. This is also demonstrated in an in vivo human study. After consumption of
      dark chocolate and cocoa powder, the lower density lipoproteins isolated from
      plasma were protected from oxidation compared to the lipoproteins isolated after
      cocoa butter consumption, which were put under oxidative stress. In an animal
      model of atherosclerosis, cocoa powder at a human dose equivalent of two dark
      chocolate bars per day significantly inhibited atherosclerosis, lowered
      cholesterol, low-density lipoprotein, and triglycerides, raised high-density
      lipoprotein, and protected the lower density lipoproteins from oxidation.
      Chocolate has thus been shown to have potential beneficial effects with respect
      to heart disease.

PMID- 17032012
TI  - Properties of high-quality long natural cellulose fibers from rice straw.
AB  - This paper reports the structure and properties of novel long natural cellulose
      fibers obtained from rice straw. Rice straw fibers have 64% cellulose with 63%
      crystalline cellulose, strength of 3.5 g/denier (450 MPa), elongation of 2.2%,
      and modulus of 200 g/denier (26 GPa), similar to that of linen fibers. The rice
      straw fibers reported here have better properties than any other natural
      cellulose fiber obtained from an agricultural byproduct. With a worldwide annual
      availability of 580 million tons, rice straw is an annually renewable, abundant,
      and cheap source for natural cellulose fibers. Using rice straw for high-value
      fibrous applications will help to add value to the rice crops, provide a
      sustainable resource for fibers, and also benefit the environment.

PMID- 17032014
TI  - Extraction of recombinant dog gastric lipase from transgenic corn seed.
AB  - Several approaches were examined for extracting the relatively hydrophobic
      protein recombinant dog gastric lipase (rDGL) expressed in the endosperm of
      transgenic corn seed. The first approach used minimal processing of the seed
      before extraction (i.e. simple grinding of whole seed) followed by selective
      extraction to eliminate 72% of contaminant proteins without compromising rDGL
      recovery from the meal of whole grain. The second approach added defatting of the
      whole grain meal to reduce the amount of detergent in the subsequent step for
      extracting rDGL. The third approach incorporated dry-milling of the corn to
      recover an endosperm rich fraction, followed by extraction of this fraction. The
      dry milling strategy was most effective, resulting in recovery of 35 U rDGL/g of
      corn seed (50 U/g of endosperm) with a specific activity of 9 U/mg compared to 22
      U and 3 U/mg for the first strategy and 36 U and 3.7 U/mg for the second. The
      reductions in host protein contamination and lower detergent levels of the
      endosperm route should simplify downstream purification steps.

PMID- 17032013
TI  - High content of resveratrol in lettuce transformed with a stilbene synthase gene
      of Parthenocissus henryana.
AB  - Resveratrol (trans-3,5,4'-trihydroxystilbene) is a plant phytoalexin which has
      positive effects on human health. Stilbene synthase (STS) is a key enzyme
      involved in resveratrol biosynthesis. To construct a vector for STS expression in
      lettuce plant, a cDNA-encoding STS of Parthenocissus henryana was fused to the
      Cauliflower mosaic virus (CaMV) 35S promoter, and the bar gene was used as a
      selective marker gene. To increase the expression of STS, the expression cassette
      was flanked by MARs. In transgenic lettuce plants, an additional compound was
      identified as resveratrol by HPLC and ESI-MS. Quantitative analysis showed that
      the average content of resveratrol reached 56.40 +/- 5.52 microg/g leaf fresh
      weight, which was comparable to the amount in grape skin. Anticancer assay in
      HeLa cells revealed that apoptosis was induced by 200 microM of resveratrol
      extracted from transgenic lettuce.

PMID- 17032015
TI  - Reinvestigation of the effect of heat pretreatment of corn fiber and corn germ on
      the levels of extractable tocopherols and tocotrienols.
AB  - We previously reported that heat pretreatment of corn fiber (150 degrees C, 1 h)
      caused a tenfold increase in the levels of extractable gamma-tocopherol. The
      current study was a reinvestigation of the previous effect, using improved
      methods (HPLC with fluorescence detection, diode-array UV detection, and mass
      spectrometry) for tocol analysis. Heat pretreatment did not cause an increase in
      the levels of any of the tocopherols or tocotrienols in corn fiber oil, but
      lowered the levels of three of the tocols and had no effect on the levels of the
      other two tocols. Heat pretreatment of corn germ had a similar effect. UV and
      mass spectra indicated that the peak that we had identified as gamma-tocopherol
      in our previous report was probably a mixture of oxidation products of
      triacylglycerols. Thus, heat treatment of corn germ or other corn-oil containing
      fractions at high temperatures leads to decreases in gamma-tocopherol, gamma
      tocotrienol, and delta-tocotrienol and to the production of triacylglycerol
      oxidation products.

PMID- 17032016
TI  - Increase in the permeability of tonoplast of garlic (Allium sativum) by
      monocarboxylic acids.
AB  - Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak
      organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No
      color was formed upon treatment with other weak organic acids, such as citric and
      malic acids, and the inorganic hydrochloric acid under the same conditions. To
      understand the significance of monocarboxylic acids and their differing function
      from that of other acids, acetic acid was compared with organic acids citric and
      malic and the inorganic hydrochloric acid. The effects of these acids on the
      permeability of plasma and intracellular membrane of garlic cells were measured
      by conductivity, light microscopy, and transmission electron microscopy. Except
      for hydrochloric acid, treatment of garlic with all three organic acids greatly
      increased the relative conductivity of their respective pickling solutions,
      indicating that all tested organic acids increased the permeability of plasma
      membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold
      higher relative conductivity (approximately 90%) as compared to those
      (approximately 60%) of both citric and malic acids, implying that exposure of
      garlic cloves to acetic acid not only changed the permeability of the plasma
      membrane but also increased the permeability of intracellular membrane. Exposure
      of garlic to acetic acid led to the production of precipitate along the
      tonoplast, but no precipitate was formed by citric and malic acids. This
      indicates that the structure of the tonoplast was damaged by this treatment.
      Further support for this conclusion comes from results showing that the
      concentration of thiosulfinates [which are produced only by catalytic conversion
      of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the
      vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no
      thiosulfinates were detected in the pickling solution of citric and malic acids.
      Thus, all present results suggest that damage of tonoplast by treatment with
      monocarboxylates such as acetic acid may be the main reason for the greening of
      garlic.

PMID- 17032017
TI  - Chemical composition and nutritional quality of soybean meals prepared by
      extruder/expeller processing for use in poultry diets.
AB  - This research examined variation in chemical composition and nutrient quality of
      soybeans (SBs) and soybean meals (SBMs) produced at seven commercial
      extruder/expeller plants in the United States (experiment 1), as well as
      differences in amino acid digestibilities when roosters were fed SBMs extruded at
      121, 135, 150, or 160 degrees C at a U.S. pilot processing plant (experiment 2).
      In experiment 1, limited variation existed in the composition of SBs arriving at
      the plants, whereas substantial differences were noted in amino acid composition
      and protein quality of the resultant SBMs. In experiment 2, the SBMs extruded at
      121 and 135 degrees C were underprocessed as noted by high urease activities and
      lower amino acid digestibilities. Soybean meals extruded at 150 and 160 degrees C
      resulted in higher amino acid digestibilities and lower urease activities,
      indicating adequate processing. Large variation exists in the nutritional quality
      of extruder/expeller SBMs currently in the marketplace. Optimal processing
      temperatures should be >135 degrees C, and temperatures as high as 165 degrees C
      do not result in overprocessing.

PMID- 17032018
TI  - Influence of geographical origin and botanical species on the content of
      extractives in American, French, and East European oak woods.
AB  - The chemical composition of East European (Republic of Moldova, Ukraine, and
      Romania) oaks was investigated profoundly for the first time in the present study
      and compared with American and French counterparts. Taking into account the high
      natural variability of oak extractives contents, the wide-ranging sampling was
      performed for all oak origins: 276 French oaks, 102 East European oaks of both
      species (Quercus robur L. and Quercus petraea Liebl.), and 56 American oaks
      (Quercus alba). These oaks were compared with great attention paid to the
      extractives, which are most important for sensorial impact in wine or spirit
      maturation, such as ellagitannins and principal odorant substances (aromatic
      aldehydes, lactones and phenols). The substances in question were studied by
      application of HPLC and GC-MS techniques. The pattern of all studied extractive
      contents allowed adequate separation of oak samples according to their
      geographical origin or botanical species. The highest separation rate was for
      American and French oaks, whereas East European samples could be partially
      misclassified in two sets mentioned above. The most important variables for
      species discrimination were whiskey lactone related variables and ellagitannins,
      whereas the most important features for distinguishing the origin were eugenol, 2
      phenylethanol, vanillin, and syringaldehyde. These substances allowed the
      distinction of French and East European woods of the same species. With regard to
      chemical composition, East European wood held the intermediary place between
      American and French oaks according to their ellagitannin and whiskey lactone
      levels; nevertheless, it was characterized by specific high values of eugenol,
      aromatic aldehydes, and 2-phenylethanol.

PMID- 17032019
TI  - Content of gamma-oryzanol and composition of steryl ferulates in brown rice
      (Oryza sativa L.) of European origin.
AB  - The content of gamma-oryzanol and the composition of steryl ferulates were
      determined in brown rice of European origin using on-line coupled liquid
      chromatography-gas chromatography (LC-GC). Analysis of 30 brown rice samples of
      various cultivars, grown at different sites and in different seasons, revealed
      the gamma-oryzanol content to range from 26 to 63 mg/100 g. Cycloartenyl ferulate
      and 24-methylenecycloartanyl ferulate were the major components of gamma-oryzanol
      followed by campesteryl ferulate, campestanyl ferulate, and beta-sitosteryl
      ferulate. The proportions of individual steryl ferulates exhibited enormous
      variability. However, irrespectively of the great variations observed for single
      steryl ferulates, the proportions of the sum of 4,4'-dimethylsteryl ferulates
      (cycloartenyl ferulate, 24-methylenecycloartanyl ferulate) and the sum of 4
      desmethylsteryl ferulates (campesteryl ferulate, campestanyl ferulate, and beta
      sitosteryl ferulate) were rather constant. The significant natural variability
      observed for gamma-oryzanol content and composition of steryl ferulates were
      shown to be influenced by environmental conditions but not by the degree of
      maturity of rice grains.

PMID- 17032020
TI  - Enantiomeric resolution and biotoxicity of methamidophos.
AB  - Despite the fact that the biological processes of chiral pesticides are
      enantioselective, the biotoxicity of methamidophos with respect to
      enantioselectivity has so far received limited research. In this study, the
      enantiomeric separation and biotoxicity of the two enantiomers of methamidophos
      were investigated. Successful enantioseparation of methamidophos using high
      performance liquid chromatography on a Chiralcel OD column was achieved. As
      indicated by the optical rotation and circular dichroism detection, (+)
      methamidophos was eluted prior to (-)-methamidophos. The t test at the 95% level
      of confidence indicated significant differences between the enantiomers in their
      in vitro inhibition toward acetylcholinesterases of bovine erythrocytes and
      Electrophorus electricus and in vivo acute aquatic toxicity to Daphnia magna. The
      in vitro assays showed that (-)-methamidophos was about 8.0-12.4 times more
      potent to the enzymes than its (+)-form. In contrast, the (+)-enantiomer was 7.0
      times more toxic to D. magna in 48 h tests. The toxicity of racemic methamidophos
      was intermediate in both in vitro and in vivo bioassays. These results suggest
      that the biotoxicity of chiral OPs to nontargeted organisms is enantioselective
      and therefore should be reevaluated with their pure enantiomers.

PMID- 17032021
TI  - Electrochemical investigation of the effect of pH and solvent on amitraz
      stability.
AB  - The widespread use of the pesticide amitraz for pest control of crops, livestock
      and honeybees has warranted several studies aimed at understanding the
      degradation of this compound during storage and use. In particular the
      degradation of amitraz and the nature of the toxicologically significant
      intermediates formed owing to pH and solvent type has been examined. In this
      study we report on the use of electrochemical methods to monitor amitraz
      degradation and to identify the major intermediates formed. While this study
      examines the use of rapid voltammetric methods for such analyses, it also
      resolves earlier studies showing the rapid degradation of amitraz to 2,4
      dimethylaniline without formation of intermediates first, and also suggests that
      the degradation of amitraz to 2,4-dimethylphenylformamide and to 2,4
      dimethylaniline is more rapid than previously observed at pH above 3. These
      studies also showed that amitraz degrades to dimethylphenylformamide in ethanol
      and methanol, and is stable in both acetonitrile and dimethylsulphoxide.

PMID- 17032022
TI  - Treatment of antibiotics and antibiotic resistant bacteria in swine wastewater
      with free chlorine.
AB  - Recent recognition of the occurrence of antibiotics in the environment has
      highlighted concerns regarding potential threats of antibiotics to humans and
      wildlife. Antibiotics are commonly applied to animals to prevent diseases and
      promote growth, making livestock agriculture a major source of antibiotic
      pollution. The purpose of our study was to examine chlorination technology as a
      method for preventing the release of antibiotics as well as antibiotic-resistant
      bacteria into the environment from concentrated animal feeding operations.
      Wastewaters from various sites of two anaerobic lagoon systems, one aerated and
      the other not, on a swine facility were investigated. Each system consisted of a
      primary treatment lagoon and a subsequent polishing lagoon. Free chlorine (or
      monochloramine for comparison) was applied to oxidize antibiotics and to
      disinfect lagoon bacteria as well. Results indicate that aeration substantially
      improves lagoon functionality, thereby adding both organic and ammonia removal.
      Ammonia present in the wastewaters plays a critical role in antibiotics
      decomposition and bacterial inactivation due to its rapid competition for free
      chlorine to form monochloramine. Generally, a chlorine dose close to breakpoint
      is required to achieve complete removal of antibiotics, leading to high
      consumption of free chlorine in most of the wastewaters examined. However,
      because of a low ammonia concentration in the polishing lagoon wastewater of the
      aerated system, a chlorine dose of 100 mg/L can effectively achieve complete
      removal of both antibiotics and bacteria. On the basis of our experimental
      findings, a possible strategy for the treatment of swine wastewater is suggested.

PMID- 17032023
TI  - Influence of pH and soil copper on adsorption of metalaxyl and penconazole by the
      surface layer of vineyard soils.
AB  - The upper horizons of old vineyard soils have substantial copper contents due to
      the traditional use of copper-based fungicides. Total copper levels in eight
      vineyard soils in the Rias Baixas area of Galicia (northwestern Spain) ranged
      from 60 to 560 mg kg(-1) (mean +/- SD = 206 +/- 170 mg kg(-1)). The adsorption of
      the fungicides metalaxyl (pK(a) = 1.41) and penconazole (pK(a) = 2.83) by these
      soils was determined using fungicide solutions of pH 2.5 and 5.5, and desorption
      of fungicide adsorbed at pH 5.5 was also determined. In all cases, Freundlich
      equations were fitted to the data with R (2) > 0.96. Penconazole was adsorbed and
      retained more strongly than metalaxyl, with K(F) values more than an order of
      magnitude greater. In the desorption experiments, both fungicides exhibited
      hysteresis. Soil copper content hardly affected the adsorption of metalaxyl, but
      K(F) values for adsorption of penconazole increased at a rate of about 0.1 mL(n)
      (microg of penconazole)(1-n) (microg of Cu)(-1), which is attributed to the
      formation of Cu(2+)-penconazole complexes with greater affinity for soil colloids
      than penconazole itself. Because the dependence of K(F) for penconazole
      adsorption on copper content was the same at both pH values, complex formation
      appears not to have been affected by the solubilization of 6-17% of soil copper
      at pH 2.5. A similar copper dependence, or lack of dependence, was observed when
      100-1000 mg kg(-1) of copper was added as Cu(NO(3))(2).2H(2)O to the solutions
      from which the fungicides were adsorbed.

PMID- 17032024
TI  - Sorption-desorption of imidacloprid and its metabolites in soil and vadose zone
      materials.
AB  - Sorption-desorption is one of the most important processes affecting the leaching
      of pesticides through soil because it controls the amount of pesticide available
      for transport. Subsurface soil properties can significantly affect pesticide
      transport and the potential for groundwater contamination. This research
      characterized the sorption-desorption of imidacloprid (1-[(6-chloro-3-pyridinyl)
      methyl]-N-nitro-2-imidazolidinimine) and three of its metabolites, 1-[(6-chloro-3
      pyridinyl)methyl]-2-imidazolidinone (imidacloprid-urea), 1-[(6-chloro-3
      pyridinyl)methyl]-4,5-dihydro-1H-imidazol-2-amine (imidacloprid-guanidine), and 1
      [(6-chloro-3-pyridinyl)methyl]-1H-imidazol-2-amine (imidacloprid-guanidine
      olefin), as a function of changing soil properties with depth in two profiles
      extending from the surface to a depth of 1.8 or 8 m. Sorption of each compound
      was highly variable and hysteretic in all cases. Normalizing the sorption
      coefficients (K(f)) to the organic carbon or the clay content of the soil did not
      reduce the variability in sorption coefficients for any compound. These results
      illustrate the importance of evaluation of the sorption data used to predict
      potential mobility. Understanding the variability of soil properties and
      processes as a function of depth is necessary for accurate prediction of
      pesticide dissipation.

PMID- 17032025
TI  - Reactions of hydrated electrons with triazine derivatives in aqueous medium.
AB  - A study is made of the kinetics and mechanism of the reaction of radiolytically
      produced hydrated electron (e-(aq)) with some triazine derivatives [1,3,5
      triazine (T), 2,4,6-trimethoxy-1,3,5-triazine (TMT), 2,4-dioxohexahydro-1,3,5
      triazine (DHT), 6-chloro N-ethyl N-(1-methylethyl)-1,3,5-triazine 2,4-diamine
      (atrazine, AT), and cyanuric acid (CA)] in aqueous medium using pulse and steady
      state radiolysis techniques. The second-order rate constants were determined from
      the pseudo first-order decay of e(-)(aq) in the presence of triazines at 720 nm,
      and the values obtained with T, TMT, AT, and CA are in the order of 10(9) dm(3)
      mol(-1) s(-1) and that of DHT was 10(8) dm(3) mol(-1) s(-1) at pH 6. The
      transient absorption spectra from the reaction of e(-)(aq) with T and TMT are
      characterized by their lambda(max) at 310 nm, and those of DHT and CA are around
      280 and 290 nm, respectively. However, a very weak and featureless absorption
      spectrum is obtained from AT. On the basis of the spectral evidence and on the
      quantitative electron transfer from the transient intermediates to the oxidant,
      methyl viologen (MV(2+)), the intermediate radicals are assigned to N-protonated
      electron adducts (with the unpaired spin density at carbon) of triazines. The
      degradation profiles, monitored as the disappearance of parent triazine
      concentrations as a function of dose, obtained with AT, TMT, CA, and DHT,
      highlight the potential use of e-(aq) in the degradation of triazines.

PMID- 17032026
TI  - Volatile compounds in the skin and pulp of Queen Anne's pocket melon.
AB  - The quantitative distribution of volatile compounds in the skin and pulp of Queen
      Anne's pocket melon [Cucumis melo var. dudaim (L.) Naudin] has been investigated.
      Volatile compounds were extracted by liquid-liquid microextraction (LLME) using
      chloroform and analyzed by GC-FID and GC-MS. Sixty volatiles, including 20
      esters, 15 alcohols, 7 lactones, 7 aldehydes and ketones, 6 sulfur compounds, and
      5 C(6) compounds, have been identified. Among them, 38 were reported for the
      first time in pocket melon, 10 of them have been, however, labeled "tentatively
      identified". The results showed that the levels of volatiles in skin were
      significantly higher than those observed in pulp. Eugenol, the major constituent
      in skin (15.3%), thioether esters, and lactones were thought to contribute
      significantly to the unique aroma of the pocket melon. Finally, the distribution
      of lactones was also found to be different in skin and pulp according to their
      carbon chain length.

PMID- 17032027
TI  - Rapid method for quantitative analysis of the aroma impact compound, 2-acetyl-1
      pyrroline, in fragrant rice using automated headspace gas chromatography.
AB  - A rapid method employing static headspace gas chromatography (HS-GC) has been
      developed and validated for quantitative analysis of the impact aroma compound, 2
      acetyl-1-pyrroline (2AP), in grains of fragrant rice. This developed method
      excludes wet extraction, and the rice headspace volatiles are brought directly
      and automatically to GC analysis. The conditions of the static HS autosampler
      were optimized to achieve high recovery and sensitivity. The most effective
      amount of rice sample used was 1 g, which provided 51% recovery and a linear
      multiple headspace extraction (MHE) plot of the peak area of 2AP. The sensitivity
      of the method was enhanced by utilizing a megabore fused silica capillary column
      in conjunction with a nitrogen-phosphorus detector (NPD). Method validations
      performed for both static HS-GC-FID and HS-GC-NPD demonstrated linear calibration
      ranges of 20-10 000 (r(2) = 0.9997) and 5-8000 (r(2) = 0.9998) ng of 2AP/g of
      rice sample, respectively. The limits of detection for both systems were 20 and 5
      ng of 2AP, and the limits of quantitation were 0.30 and 0.01 g of brown rice
      sample, respectively. Reproducibility calculated as intraday and interday
      coefficients of variation were 3.25% RSD (n = 15) and 3.92% RSD (n = 35),
      respectively, for SHS-GC-FID and 1.87% RSD (n = 15) and 2.85% RSD (n = 35),
      respectively, for SHS-GC-NPD. The method was found to be effective when applied
      to the evaluation of aroma quality, based on 2AP concentrations, of some fragrant
      rice samples.

PMID- 17032028
TI  - Characterization of volatiles in extracts from oak chips obtained by accelerated
      solvent extraction (ASE).
AB  - Sixteen commercially available oak chips, differing in origin (French or
      American) and toasting level, were extracted by an accelerated solvent extraction
      method and characterized by their volatile composition. About 80 compounds were
      identified and quantified, a great part of them from the thermodegradation of
      lignin and cellulose. One furanone (solerone) and two C-13 norisoprenoids (3-oxo
      alpha-ionol and a 3-oxoretro-alpha-ionol isomer) were also tentatively identified
      and reported for the first time in toasted wood. Quantitative data demonstrated
      the oak chips to be not so different from the composition of light- or medium
      toasted wood barrels, which was reported by other authors. The same data suggest
      that toasting level had the strongest influence on the volatile composition of
      chip samples. Phenyl ketones, volatile phenols, and some furanic compounds were
      the most influenced. On the other hand, the influence of wood origin was found to
      be weaker.

PMID- 17032029
TI  - Volatile compound biosynthesis by green leaves from an Arabidopsis thaliana
      hydroperoxide lyase knockout mutant.
AB  - The degradation of polyunsaturated fatty acids through the lipoxygenase pathway
      is responsible for the production of volatile compounds that confer green sensory
      notes to the aroma of fruits and vegetables. The peroxidation of free linoleic or
      linolenic acid by action of lipoxygenase and then the lysis of the resulting
      hydroperoxides, through a reaction catalyzed by the hydroperoxide lyase, are the
      most determinant steps of this pathway. This work analyzes the impact of the
      hydroperoxide lyase depletion on the volatile composition of leaves from
      Arabidopsis thaliana that is used as model system. The work involves the
      characterization of the volatile profiles of the Arabidopsis plants followed by a
      study of the metabolism of radio-labeled linoleic acid and determinations of
      lipoxygenase activity. Hydroperoxide lyase-knockout plants show similar levels of
      C6 compounds, but the total amount of C5 compounds is 4-fold higher in mutant
      plants. The perspectives of production of vegetable products with a modified
      aroma by genetically engineering the lipoxygenase pathway were discussed with
      respect to the statistical results.

PMID- 17032030
TI  - Cell wall composition of smooth bromegrass plants selected for divergent fiber
      concentration.
AB  - Neutral detergent fiber (NDF) is considered the single best laboratory predictor
      of voluntary intake by ruminant livestock, creating interest in using NDF as a
      selection criterion in forage breeding programs. Because genetic reductions in
      NDF lead to increases in dry matter digestibility but not to changes in
      digestibility of the NDF fraction, we postulated that low-NDF plants do not have
      altered compositions of their cell walls. We tested this hypothesis using clones
      of smooth bromegrass (Bromus inermis Leyss.) with divergent NDF concentrations.
      High-NDF and low-NDF plants did not differ in cell wall concentrations or in the
      concentrations of any cell wall component (fucose, arabinose, rhamnose,
      galactose, glucose, xylose, mannose, uronic acids, and lignin). Instead, low-NDF
      plants had a cell wall that was more susceptible to solubilization in neutral
      detergent solution, suggesting that their cell walls were less well-developed as
      compared to high-NDF plants. NDF should not be used as a substitute for cell wall
      concentration in forage plants.

PMID- 17032031
TI  - Inhibitory effect of known antioxidants and of press juice from herring (Clupea
      harengus) light muscle on the generation of free radicals in human monocytes.
AB  - Reactive oxygen species (ROS) can cause oxidative stress, which has been linked
      to various diseases. It has been suggested that antioxidant-rich foods can reduce
      such oxidative stress. However, the lack of suitable model systems to screen for
      in vivo effects of food-derived antioxidants has prevented a clear consensus in
      this area. In this study, the aim was to use a single-cell model system (human
      monocyte) to evaluate whether certain pure antioxidants and complex muscle
      extracts (herring light muscle press juice, PJ) could prevent ROS formation under
      in vivo like conditions. ROS were excreted from the monocytes upon stimulation
      with phorbol myristate acetate and were then detected as isoluminol-enhanced
      chemiluminescence (CL). Adding 2000 units of catalase and 50 units of superoxide
      dismutase to the monocytes model lowered the CL response by 35 and 86%,
      respectively. Ascorbate (14.1 mM) lowered the response by 99%, alpha-tocoperhol
      (188 microM) by 37%, and Trolox (50 microM) by almost 100%. Crude herring PJ gave
      a dose-dependent reduction in the CL response. At 10, 100, and 1000 times
      dilution, the PJ reduced the CL signal by 93, 60.5, and 10.6%. PJ fractionated
      into low molecular weight (LMW) (<1000 Da) and high molecular weight (>3500 Da)
      fractions decreased the CL response by 52.9 and 71.4%, respectively, at a 100
      fold dilution. Evaluation of the PJ samples in the oxygen radical absorbance
      capacity test indicated that proteins may be the primary radical scavenging
      compounds of PJ, whereas the ROS-preventing effect obtained from the LMW fraction
      may also be attributed to other mechanisms. Thus, this study proved that the
      monocyte assay can be a useful tool for studying whether food-derived
      antioxidants can limit ROS production under physiologically relevant conditions.
      It also showed that herring contains numerous aqueous compounds demonstrating
      antioxidative effects in the monocyte model system.

PMID- 17032032
TI  - Molecular cloning and characterization of an alpha-amylase occurring in the pulp
      of ripening bananas and its expression in Pichia pastoris.
AB  - Alpha-amylases (EC 3.2.1.1) are glycosyl hydrolases with endoglycolytic activity
      on the alpha-1,4-d-glucosidic linkages in starch. In bananas, the mobilization of
      starch accounts for sugar accumulation during ripening, and among several
      hydrolytic enzymes, alpha-amylase is the only enzyme argued to be able to attack
      the intact granules, indicating a pivotal role for this enzyme. A 1953 bp full
      length banana alpha-amylase cDNA (MAmy), encoded for a sequence of 416 amino
      acids, was cloned and used for heterologous expression in Pichia pastoris. The
      cloned MAmy presented the highly conserved motifs common to alpha-amylases, and
      the amylolytic activity of the extracts from yeast transformed with MAmy
      demonstrated that it encodes for a functional alpha-amylase, suggesting a
      putative role for this gene in starch degradation during fruit ripening.

PMID- 17032033
TI  - Starter bacteria are the prime agents of lipolysis in cheddar cheese.
AB  - To assess the contribution of starter lactic acid bacteria (LAB) to lipolysis in
      Cheddar cheese, the evolution of free fatty acids (FFAs) was monitored in Cheddar
      cheeses manufactured from pasteurized milks with or without starter. Starter-free
      cheeses were acidified by a combination of lactic acid and glucono-delta-lactone.
      Starter cultures were found to actively produce FFAs in the cheese vat, and mean
      levels of FFAs were significantly higher in starter cheeses over ripening. The
      contribution of nonstarter LAB toward lipolysis appears minimal, especially in
      starter-acidified cheeses. It is postulated that the moderate increases in FFAs
      in Cheddar cheese are primarily due to lack of access of esterase of LAB to
      suitable lipid substrate. The results of this study indicate that starter
      esterases are the primary contributors to lipolysis in Cheddar cheese made from
      good quality pasteurized milk.

PMID- 17032034
TI  - Study of the effect of soy proteins on the acid-induced gelation of casein
      micelles.
AB  - The objective of this research was to understand whether addition of soy protein
      to milk protein affects the properties of acid-induced casein gels. Different
      samples were prepared by suspending casein micelles pellets in milk serum
      containing soy proteins or whey proteins as well as mixtures of the two proteins.
      Glucono-delta-lactone was added, and the changes in apparent size (in diluted
      systems) as well as the viscoelastic properties of the mixtures were measured.
      Size exclusion chromatography was also carried out to characterize the soluble
      phase of the various mixtures before and after heating. Soy protein affected the
      gelation of the mixtures; however, not to the same extent as whey proteins, which
      dominated formation of the network in soy-whey-casein systems. It was concluded
      that, up to a critical ratio of soy/whey proteins, soy proteins can be
      incorporated in the mix without a significant change in structure of the casein
      gels.

PMID- 17032035
TI  - Three-year comparison of the content of antioxidant microconstituents and several
      quality characteristics in organic and conventionally managed tomatoes and bell
      peppers.
AB  - Understanding how the environment and production and cultivation practices
      influence the composition and quality of food crops is fundamental to the
      production of high-quality nutritious foods. In this 3-year study, total
      phenolics, percent soluble solids, ascorbic acid, and the flavonoid aglycones
      quercetin, kaempferol, and luteolin were measured in two varieties of tomato
      (Lycopersicon esculentum L. cv. Ropreco and Burbank) and two varieties of bell
      peppers (Capsicum annuum L. cv. California Wonder and Excalibur) grown by
      certified organic and conventional practices in a model system. Significantly
      higher levels of percent soluble solids (17%), quercetin (30%), kaempferol (17%),
      and ascorbic acid (26%) were found in Burbank tomatoes (fresh weight basis; FWB),
      whereas only levels of percent soluble solids (10%) and kaempferol (20%) were
      significantly higher in organic Ropreco tomatoes (FWB). Year-to-year variability
      was significant, and high values from 2003 influenced the 3-year average value of
      quercetin reported for organic Burbank tomatoes. Burbank tomatoes generally had
      higher levels of quercetin, kaempferol, total phenolics, and ascorbic acid as
      compared to Ropreco tomatoes. Bell peppers were influenced less by environment
      and did not display cropping system differences.

PMID- 17032036
TI  - Oxidative stability of algal oils as affected by their minor components.
AB  - Algal oils, namely, arachidonic acid single-cell oil (ARASCO), docosahexaenoic
      acid single-cell oil (DHASCO), and a single-cell oil rich in both docosahexaenoic
      acid and docosapentaenoic acid (OMEGA-GOLD oil), were evaluated for their
      oxidative stability, as such and after stripping of their minor components, in
      the dark at 60 degrees C and under fluorescent light at 27 degrees C. Several
      analytical methods were used to assess the oxidative stability of these oils. Oil
      extracts were also investigated for their scavenging of 1,1-diphenyl-2
      picrylhydrazyl radical by a spectrophotometric method and by measuring their
      total phenolic contents. The results indicated that minor oil constituents play a
      major role in their oxidative stability in the dark as well as under fluorescent
      light. The stability of the oils was dictated by their fatty acid composition,
      total tocopherols, and the type of pigment present. DHASCO contained a
      significant level of natural radical scavengers and phenolic compounds that
      contributed to its higher stability compared to the ARASCO and OMEGA-GOLD oils.
      Thus, the importance of minor components in the stability of the oils examined
      was demonstrated.

PMID- 17032037
TI  - Comparative studies of some phenolic compounds (quercetin, rutin, and ferulic
      acid) affecting hepatic fatty acid synthesis in mice.
AB  - The physiological activities of some phenolic compounds affecting hepatic fatty
      acid synthesis in mice were compared. Male ICR mice were fed an experimental diet
      containing 1% quercetin dihydrate, rutin, or ferulic acid or a control diet free
      of phenolic compounds for 15 days. Quercetin significantly lowered serum
      cholesterol and phospholipid levels in mice. Also, the serum triacylglycerol
      level was considerably lower in mice fed the quercetin-containing diet than in
      those fed a diet free of phenolic compounds, although the difference was not
      significant. Rutin and ferulic acid did not affect these parameters. Quercetin
      significantly reduced the activity and mRNA levels of various enzymes involved in
      hepatic fatty acid synthesis. Rutin reduced a few of the parameters for
      lipogenesis, but ferulic acid did not affect any of the parameters. It was
      suggested that a reduction in hepatic lipogenesis is the mechanism underlying the
      hypolipidemic effect of quercetin.

PMID- 17032038
TI  - Effectiveness of ionizing radiation in reducing furan and acrylamide levels in
      foods.
AB  - Furan and acrylamide are two possible carcinogens commonly found in many
      thermally processed foods. The possibility of using ionizing radiation to reduce
      the levels of thermally induced furan and acrylamide in water and selected foods
      was investigated. Aqueous furan solutions, and foods (frankfurters, sausages,
      infant sweet potatoes) that contained furan were irradiated to various doses of
      gamma-rays. Water and oil spiked with acrylamide and potato chips (a known
      acrylamide-containing food) were also irradiated. In addition, possible
      irradiation-induced formation of acrylamide in glucose and asparagine solutions
      was analyzed. Results showed that irradiation at 1.0 kGy destroyed almost all
      furan in water. In frankfurters, sausages, and infant sweet potatoes, the rate of
      irradiation-induced destruction of furan was much lower than the rate in water,
      although significant reductions in furan levels were observed in all foods.
      Irradiation at 2.5-3.5 kGy, doses that can inactivate 5-log of most common
      pathogens, reduced furan levels in the food samples by 25-40%. Similarly to
      furan, acrylamide in water was also sensitive to irradiation. After 1.5 kGy of
      irradiation, most of the acrylamide was degraded. Irradiation, however, had a
      very limited effect on acrylamide levels in oil and in potato chips, even at a
      dose of 10 kGy. No detectable acrylamide was formed in the mixture of asparagine
      and glucose upon irradiation. These results suggest that a low dose of
      irradiation easily destroys furan and acrylamide in water. In real foods,
      however, the reduction of furan was less effective than in water, whereas the
      reduction in acrylamide was minimal.

PMID- 17032039
TI  - Mechanisms of heme protein-mediated lipid oxidation using hemoglobin and
      myoglobin variants in raw and heated washed muscle.
AB  - The hemoglobin variant rHb 0.1, which possesses a decreased ability to form
      subunits, stimulated lipid oxidation in washed fish muscle less effectively as
      compared to wild-type hemoglobin (rHb 0.0). This could be due to the lower hemin
      affinity and more rapid autoxidation rate of subunits as compared to tetramers.
      To differentiate between hemin affinity and autoxidation effects, ferrous V68T Mb
      was compared to ferrous wild-type myoglobin (WT Mb). WT Mb has a more rapid hemin
      loss rate (25-fold) than does V68T, while V68T autoxidized more rapidly than did
      WT Mb (60-fold). Ferrous WT Mb promoted TBARS and lipid peroxide formation more
      rapidly than did ferrous V68T (p < 0.01). This indicated hemin loss rate was more
      critical in determining onset of lipid oxidation as compared to autoxidation
      rate. Hemin alone was capable of stimulating lipid oxidation. Albumin enhanced
      the ability of hemin to promote lipid oxidation. MetMb promoted lipid oxidation
      more effectively than did ferrous Mb, which could be due to the lower hemin
      affinity of metMb as compared to that of ferrous Mb. EDTA, an iron chelator, had
      no effect on the rate or extent of lipid oxidation mediated by Mb in the cooked
      system. Variants with a 975-fold range of hemin affinities promoted lipid
      oxidation with equivalent efficacy in cooked washed cod contrary to results in
      uncooked washed cod. The cooking temperatures apparently denature the globin and
      release hemin reactant to such an extent that the impact of hemin affinity on
      lipid oxidation observed in the raw state is negated in the cooked state. These
      studies collectively suggest released hemin is of primary importance in promoting
      lipid oxidation in raw and cooked washed fish muscle.

PMID- 17032040
TI  - Prediction of the ripening times of ewe's milk cheese by multivariate regression
      analysis of capillary electrophoresis casein fractions.
AB  - The effect of the ripening time on the proteolytic process in cheeses made from
      ewe's milk during a 139-day ripening period was monitored by the use of capillary
      electrophoresis of pH 4.6 insoluble fraction. Totals of 18 and 21 peaks were
      recognized and matched in the electropherograms obtained with a fused-silica
      capillary and a neutral capillary (hydrophilically coated), respectively. These
      peaks correspond to intact ovine caseins and their hydrolysis products (alpha(s1)
      casein I, alpha(s1)-casein II, alpha(s1)-casein III, alpha(s2)-casein, beta(1)
      casein, beta(2)-casein, p-kappa-casein, alpha(s1)-I-casein, gamma(1)-casein,
      gamma(2)-casein, and gamma(3)-casein). The alpha(s)-caseins (alpha(s1)- and
      alpha(s2)-casein) displayed similar degradation pattern to one another, but
      different from those of beta-caseins (beta(1)- and beta(2)-casein). beta-Caseins
      were very much undergoing lesser degradation during the ripening time than
      alpha(s)-casein. Finally, partial least-squares regression and principal
      components regression were used to predict the ripening time in cheeses. The
      models obtained yielded good results since the root-mean-square error in
      prediction by cross validation was <8.6 days in all cases.

PMID- 17032041
TI  - Solvent-mediated disruption of bovine casein micelles at alkaline pH.
AB  - The disruption of casein micelles at alkaline pH was investigated using turbidity
      measurements. The rate and extent of disruption of casein micelles at alkaline pH
      (8.0-11.0) increased with pH. Furthermore, the extent of alkaline disruption
      increased with increasing temperature (5-40 degrees C). Preheating milk for 10
      min at 90 degrees C did not influence the extent of alkaline disruption of casein
      micelles, suggesting that whey proteins do not influence the alkaline disruption
      process. Levels of ionic calcium and serum calcium and phosphate decreased in a
      logarithmic fashion with increasing pH, indicating precipitation of calcium
      phosphate onto the casein micelles. A mechanism for alkaline disruption of casein
      micelles is proposed, in which increasing the milk pH improves the solvent
      quality for the caseins, thereby leading to the disruption of casein micelles
      into their constituent nanoclusters; increases in the net-negative charge on the
      caseins on increasing pH may contribute to micellar dissociation.

PMID- 17032042
TI  - Interaction of sodium dodecyl sulfate with watermelon chromoplasts and
      examination of the organization of lycopene within the chromoplasts.
AB  - The properties of plant-derived precipitates of watermelon lycopene were examined
      in aqueous sodium dodecyl sulfate (SDS) as part of an ongoing effort to develop
      simpler, more economical ways to quantify carotenoids in melon fruit. Levels of
      SDS >0.2% were found to increase the water solubility of lycopene in the state in
      which it was isolated from watermelon. Electron microscopy and chemical analyses
      suggested that the watermelon lycopene as isolated is packaged inside a membrane
      to form a chromoplast. Spectral peaks in the visible region of the watermelon
      chromoplasts in SDS exhibited a bathochromic shift from those in organic solvent.
      Watermelon chromoplasts in SDS exhibited pronounced circular dichroic activity in
      the visible region. Binding measurements indicated that about 120 molecules of
      SDS were bound per molecule of lycopene inside the chromoplast; likely, the
      detergent molecules are bound to the chromoplast membrane. Around 80% of the
      chromoplast-SDS complexes were retained on a 0.45 mum membrane filter. Together,
      these observations are consistent with lycopene in a J-type chiral arrangement
      inside a membrane to form a chromoplast. The binding of SDS molecules to the
      chromoplast membrane form a complex that is extensively more water-soluble than
      the chromoplast alone.

PMID- 17032043
TI  - Metabolite profiling of wheat grains (Triticum aestivum L.) from organic and
      conventional agriculture.
AB  - In some European community countries up to 8% of the agricultural area is managed
      organically. The aim was to obtain a metabolite profile for wheat (Triticum
      aestivum L.) grains grown under comparable organic and conventional conditions.
      These conditions cannot be found in plant material originating from different
      farms or from products purchased in supermarkets. Wheat grains from a long-term
      biodynamic, bioorganic, and conventional farming system from the harvest 2003
      from Switzerland were analyzed. The presented data show that using a high
      throughput GC-MS technique, it was possible to determine relative levels of a set
      of 52 different metabolites including amino acids, organic acids, sugars, sugar
      alcohols, sugar phosphates, and nucleotides from wheat grains. Within the
      metabolites from all field trials, there was at the most a 50% reduction
      comparing highest and lowest mean values. The statistical analysis of the data
      shows that the metabolite status of the wheat grain from organic and mineralic
      farming did not differ in concentrations of 44 metabolites. This result indicates
      no impact or a small impact of the different farming systems. In consequence, we
      did not detect extreme differences in metabolite composition and quality of wheat
      grains.

PMID- 17032044
TI  - Enzymatic hydrolysis of flavonoids and pectic oligosaccharides from bergamot
      (Citrus bergamia Risso) peel.
AB  - Pectinolytic and cellulolytic enzymes (Pectinase 62L, Pectinase 690L, and
      Cellulase CO13P) were used to evaluate the solubilization of carbohydrates and
      low molecular weight flavonoids from bergamot peel, a major byproduct of the
      essential oil industry. The enzymes were characterized for main-chain and side
      chain polysaccharide hydrolyzing activities and also against pure samples of
      various flavonoids previously identified in bergamot peel to determine various
      glycosidase activities. The addition of Pectinase 62L or 690L alone, or the
      combination of Pectinase 62L and Cellulase CO13P, was capable of solubilizing
      between 70 and 80% of the bergamot peel, and up to 90% of the flavonoid
      glycosides present were cleaved to their aglycones. Cellulase CO13P alone
      solubilized 62% of the peel but had no deglycosylating effect on the flavonoid
      glycosides. Over a 24-h time course, a rapid release of cell wall carbohydrates
      was observed after treatment with Pectinase 62L, with a concurrent gradual
      hydrolysis of the flavonoid glycosides. Size-exclusion chromatography of the
      solubilized extract showed that after 24-h incubation, the majority of the
      solubilized carbohydrates were present as monosaccharides with a smaller
      proportion of oligosaccharides.

PMID- 17032045
TI  - Chemical characterization of oak heartwood from Spanish forests of Quercus
      pyrenaica (Wild.). Ellagitannins, low molecular weight phenolic, and volatile
      compounds.
AB  - The need for new sources of quality wood supply for cooperage has led to looking
      into the possibility of utilizing Quercus pyrenaica Wild. oak, a species native
      to the Iberian peninsula, as an alternative to other European (Quercus robur and
      Qurecus petraea) and American (Quercus alba) oaks. The low molecular weight
      phenolic composition, ellagitannins, and volatile compounds (including a wide
      range of compound families such as volatile phenols, furanic compounds, lactones,
      phenyl ketones, other lignin-derived compounds, and volatile compounds related to
      off-flavors) of green heartwood from Spanish forest regions were studied by HPLC
      and GC, in order to know its enological characteristics. The chemical composition
      of Q. pyrenaica is similar to that of other species commonly used in cooperage to
      make barrels, showing only quantitative differences that were more significant
      with respect to American than to French species. The four provenance regions
      studied showed similar chemical composition, with high variability among
      individuals, often higher than the variability among regions of provenance, but
      in line with that described in other European and American oak woods. Therefore,
      this species must be considered to be suitable for aging wine.

PMID- 17032046
TI  - Protein analysis of honeys by fast protein liquid chromatography: application to
      differentiate floral and honeydew honeys.
AB  - Fast protein liquid chromatography on a Superdex 75 HR column has been applied to
      analyze the proteins of 29 honeys, 12 of floral origin and 17 from honeydew. The
      molecular masses were comprised between 13100 and 94000 Da. Seven peaks have been
      separated; four of them were present in all of the honeys, and three were only
      present in some honeys. Direct observation of the chromatograms of the floral and
      honeydew honeys did not reveal any information about their botanical origins.
      However, both types of honeys can be distinguished with the percentages of the
      areas of four of the seven chromatographic peaks obtained.

PMID- 17032047
TI  - Flavonoids from italian multifloral honeys reduce the extracellular ferricyanide
      in human red blood cells.
AB  - In this study we investigated some biological properties of flavonoids recovered
      in the aqueous (AqE) and ether (EtE) extracts from four Italian multifloral
      honeys. In particular, a cell-free assay was employed to detect direct reduction
      of ferricyanide, whereas an assay using intact human erythrocytes was used to
      measure the ability to donate electrons to a trans-plasma membrane
      oxidoreductase. It was found that the AqE displays greater "in vitro"
      ferricyanide-reducing activity than the EtE but, unlike the latter, is virtually
      ineffective in the cell-based assay. Uptake studies employing high-performance
      liquid chromatography/mass spectrometry (HPLC/MS) showed that the different
      results were explained by the inability of AqE components to cross the
      erythrocyte plasma membrane and by the excellent uptake of EtE flavonoids, which,
      once within the cell, donate electrons to the membrane oxidoreductase to
      efficiently reduce extracellular oxidants. The latter property appears to depend
      on the content of ether-soluble flavonoids in the starting honeys.

PMID- 17032048
TI  - Changes in organic acids and sugars during early stages of development of acidic
      and acidless citrus fruit.
AB  - Most of the studies on organic acids and sugars in citrus were performed during
      fruit maturation, and less is known before this stage of development. The aim of
      our study was to investigate acids and sugars in lemon, lime, and orange from
      fruit-set toward development. We chose to compare organic acid and sugar
      accumulation among acidic and acidless varieties within three species. We
      estimated the acidity by titrimetry and quantified the concentrations of seven
      organic acids and three sugars by reverse HPLC. During the first 50 days of
      development, quinic acid was the major organic acid whatever the variety.
      Afterward, citric acid predominated in acidic varieties, while in acidless, malic
      acid exceeded it. Fructose substituted citric acid in acidless and could be
      synthesized either from citric acid or directly from glucose. Our results
      provided the first complete report on sugar and organic acid accumulation during
      the early stages of fruit development in several citrus varieties.

PMID- 17032049
TI  - Selective recovery of tagatose from mixtures with galactose by direct extraction
      with supercritical CO2 and different cosolvents.
AB  - A selective fractionation method of carbohydrate mixtures of galactose/tagatose,
      using supercritical CO(2) and isopropanol as cosolvent, has been evaluated.
      Optimization was carried out using a central composite face design and
      considering as factors the extraction pressure (from 100 to 300 bar), the
      extraction temperature (from 60 to 100 degrees C), and the modifier flow rate
      (from 0.2 to 0.4 mL/min, which corresponded to a total cosolvent percentage
      ranging from 4 to 18% vol). The responses evaluated were the amount (milligrams)
      of tagatose and galactose extracted and their recoveries (percent). The
      statistical analysis of the results provided mathematical models for each
      response variable. The corresponding parameters were estimated by multiple linear
      regression, and high determination coefficients (>0.96) were obtained. The
      optimum conditions of the extraction process to get the maximum recovery of
      tagatose (37%) were 300 bar, 60 degrees C, and 0.4 mL/min of cosolvent. The
      predicted value was 24.37 mg of tagatose, whereas the experimental value was
      26.34 mg, which is a 7% error from the predicted value. Cosolvent polarity
      effects on tagatose extraction from mixtures of galactose/tagatose were also
      studied using different alcohols and their mixtures with water. Although a
      remarkable increase of the amount of total carbohydrate extracted with polarity
      was found, selective extraction of tagatose decreased with increase of polarity
      of assayed cosolvents. To improve the recovery of extracted tagatose, additional
      experiments outside the experimental domain were carried out (300 bar, 80 degrees
      C, and 0.6 mL/min of isopropanol); recoveries >75% of tagatose with purity >90%
      were obtained.

PMID- 17032050
TI  - Different effects of microwave and ultrasound on the stability of (all-E)
      astaxanthin.
AB  - Both microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE)
      have been widely applied in the extraction of a variety of biologically active
      compounds including carotenoids due to their lower pollution to environment, high
      extraction efficiency, lower cost, and shorter extraction time as compared to
      conventional extraction techniques. However, there are few reports on their
      effects on the stability of these compounds. In the present study, the stability
      of (all-E)-astaxanthin, one of the carotenoids, was examined under the action of
      both ultrasound and microwave. Results showed that microwave induced the
      isomerization of (all-E)-astaxanthin to its Z analogues, preferentially to (13Z)
      astaxanthin as analyzed by HPLC coupled with diode array detection and LC-MS; and
      the percentage of the isomerization increased with increasing both treatment time
      and microwave power. In contrast to the microwave, the ultrasound degraded (all
      E)-astaxanthin to unidentified colorless compound(s) as suggested by HPLC
      analysis and UV/vis measurements, and the degradation likewise increased as both
      treatment time and ultrasonic power increased. The results presented here
      emphasized that both MAE and UAE techniques should be carefully used in the
      extraction of unstable compounds such as (all-E)-astaxanthin.

PMID- 17032051
TI  - NMR characterization of lignins isolated from fruit and vegetable insoluble
      dietary fiber.
AB  - Compositional information for lignins in food is rare and concentrated on cereal
      grains and brans. As lignins are suspected to have important health roles in the
      dietary fiber complex, the confusing current information derived from nonspecific
      lignin determination methods needs to be augmented by diagnostic structural
      studies. For this study, lignin fractions were isolated from kiwi, pear, rhubarb,
      and, for comparison, wheat bran insoluble dietary fiber. Clean pear and kiwi
      lignin isolates allowed for substantive structural profiling, but it is suggested
      that the significance of lignin in wheat has been overestimated by reliance on
      nonspecific analytical methods. Volume integration of NMR contours in two
      dimensional (13)C-(1)H correlation spectra shows that pear and wheat lignins have
      comparable guaiacyl and syringyl contributions and that kiwi lignins are
      particularly guaiacyl-rich (approximately 94% guaiacyl) and suggest that rhubarb
      lignins, which could not be isolated from contaminating materials, are as
      syringyl-rich (approximately 96% syringyl) as lignins from any known natural or
      transgenic fiber source. Typical lignin structures, including those newly NMR
      validated (glycerols, spirodienones, and dibenzodioxocins), and resinols
      implicated as possible mammalian lignan precursors in the gut are demonstrated
      via their NMR correlation spectra in the fruit and vegetable samples. A novel
      putative benzodioxane structure appears to be associated with the kiwi lignin. It
      is concluded that the fruits and vegetables examined contain authentic lignins
      and that the detailed structural analysis exposes limitations of currently
      accepted analytical methods.

PMID- 17032052
TI  - Effect of bread baking on the bioavailability of hydrogen-reduced iron powder
      added to unenriched refined wheat flour.
AB  - Elemental iron powders are widely used to fortify flour and other cereal
      products. Our objective was to test the hypothesis that baking enhances the
      bioavailability of elemental iron powders by oxidizing Fe(0) to Fe(2+) or Fe(3+).
      An in vitro digestion/Caco-2 cell culture model and a piglet model were used to
      measure bioavailability. Bread flour, either unfortified or fortified with
      hydrogen-reduced (HR) iron powder or FeSO(4) (300 mg Fe/kg flour), was baked into
      bread. For the in vitro studies, bread samples were treated with pepsin at pH 2,
      3, 4, 5, 6, or 7 and subsequently incubated with pancreatic enzymes at pH 7 in a
      chamber positioned above monolayers of cultured Caco-2 cells. Ferritin formation
      in the cells was used as an index of iron bioavailability. Ferritin formation in
      cells fed HR Fe bread was similar to cells fed FeSO(4) bread when the peptic
      digestion was conducted at a pH 2 but lower when the peptic phase was conducted
      at pH 3, 4, 5, 6, or 7 (P < 0.05). Pig diets containing 35% dried bread were
      prepared and fed to cross-bred (Hampshire x Landrace x Yorkshire) anemic pigs in
      two studies. The rate of increase in hemoglobin Fe over the feeding period was
      used to calculate relative biological value (RBV), an index of iron
      bioavailability. In the first pig study, RBV of HR Fe added to flour prior to
      baking was 47.9% when compared to FeSO(4) fortified flour (P < 0.05). In the
      second pig study, a third treatment consisting of unfortified bread with HR iron
      added during diet mixing (after bread baking) was included. RBVs of the HR Fe
      diet (Fe added after baking) and HR Fe diet (Fe added before baking) were 40.1%
      and 53.5%, respectively, compared to the FeSO(4) diet. Differences in RBV between
      the HR Fe (before and after baking) and FeSO(4) (before baking) treatment groups
      were significant, but the difference between the before and after HR treatment
      groups was not significant. We conclude that bread baking does not enhance the
      bioavailability of elemental iron powders.

PMID- 17032053
TI  - Jug r 4, a legumin group food allergen from walnut (Juglans regia Cv. Chandler).
AB  - Allergy to walnut is the most frequently reported tree nut allergy in the United
      States. Walnut 2S albumin, a vicilin-like protein, and a lipid transfer protein
      allergen have previously been described. Our objective was to clone and express a
      cDNA encoding a legumin group protein, assess IgE-binding with sera from walnut
      allergic patients, and investigate cross-reactivity with selected nuts. Primers
      were used to obtain the cDNA by 5' and 3' rapid amplification of cDNA ends from
      walnut mRNA. The cDNA was subcloned into the pMAL-c2X vector and the recombinant
      fusion protein, named rJug r 4, was expressed in Escherichia coli. The obtained
      cDNA encoded a precursor protein with a predicted molecular weight of 58.1 kD,
      which showed significant sequence homology to hazelnut and cashew legumin
      allergens. Serum IgE from 21 of 37 (57%) patients bound the rJug r 4 fusion
      protein. In vitro cross-reactivity was demonstrated with hazelnut, cashew, and
      peanut protein extracts.

PMID- 17032054
TI  - Effect of red wine marinades on the formation of heterocyclic amines in fried
      chicken breast.
AB  - Genotoxic heterocyclic amines (HAs) are formed via the Maillard reaction and free
      radical reaction mechanisms when meat or fish is cooked at usual cooking
      conditions. In this paper, the effect of the addition of red wine was tested to
      study if it interferes in HA formation. Fried chicken breast was the food item
      chosen, and three different red wines, characterized in terms of grape varieties,
      free amino acids, antioxidant properties, and metallic composition, were used to
      marinate meat prior to the heating process. Unmarinated samples and samples
      marinated with an ethanol-water mixture provided reference HA levels. The frying
      experiments were performed under well-controlled temperature and time conditions.
      The samples were analyzed for HA content using solid-phase extraction and LC
      MS/MS. DMIP, PhIP, MeIQx, 4,8-DiMeIQx, IFP, TMIP, harman, and norharman were
      identified in fried chicken breast. Red wine marinades were found to reduce the
      formation of some of the HAs formed. PhIP, with a reduction of up to 88%, was the
      most minimized amine, although the formation of harman was enhanced.

PMID- 17032055
TI  - Concentrations of perfluorooctanesulfonamides in Canadian total diet study
      composite food samples collected between 1992 and 2004.
AB  - Canadian Total Diet Study composite samples collected from 1992 to 2004 (n = 151)
      were analyzed for a series of perfluorooctanesulfonamides that are likely
      breakdown products or manufacturing residuals associated with
      perfluorooctylsulfonyl phosphate esters. These esters have been incorporated into
      coatings for paper and paperboard used in food packaging. N
      Ethylperfluorooctanesulfonamide (N-EtPFOSA), perfluorooctanesulfonamide, N,N
      diethylperfluorooctanesulfonamide, N-methylperfluorooctanesulfonamide, and N,N
      dimethylperfluorooctanesulfonamide were extracted using solvent extraction and
      quantified by gas chromatography-mass spectrometry. Perfluorooctanesulfonamides
      were detected in the picograms per gram to low nanograms per gram of wet weight
      range in all food groups tested-baked goods and candy, dairy, eggs, fast food,
      fish, meat, and foods to be prepared in packaging. The highest concentrations of
      total perfluorooctanesulfonamides were observed in fast food composites (from
      less than the method detection limit to 27300 pg/g of wet weight). Concentrations
      of N-EtPFOSA appeared to decrease over the sampling period (1992-2004) in French
      fries and other fast food composites; no such trend was apparent in freshwater
      fish, marine fish, and shellfish composites. A basic estimate of dietary exposure
      to perfluorooctanesulfonamides suggests that Canadians (>12 years old) are
      exposed to approximately 73 ng/person/day from these foods.

PMID- 17032058
TI  - Lentiviral gene transfer of RPE65 rescues survival and function of cones in a
      mouse model of Leber congenital amaurosis.
AB  - BACKGROUND: RPE65 is specifically expressed in the retinal pigment epithelium and
      is essential for the recycling of 11-cis-retinal, the chromophore of rod and cone
      opsins. In humans, mutations in RPE65 lead to Leber congenital amaurosis or early
      onset retinal dystrophy, a severe form of retinitis pigmentosa. The proof of
      feasibility of gene therapy for RPE65 deficiency has already been established in
      a dog model of Leber congenital amaurosis, but rescue of the cone function,
      although crucial for human high-acuity vision, has never been strictly proven. In
      Rpe65 knockout mice, photoreceptors show a drastically reduced light sensitivity
      and are subject to degeneration, the cone photoreceptors being lost at early
      stages of the disease. In the present study, we address the question of whether
      application of a lentiviral vector expressing the Rpe65 mouse cDNA prevents cone
      degeneration and restores cone function in Rpe65 knockout mice. METHODS AND
      FINDINGS: Subretinal injection of the vector in Rpe65-deficient mice led to
      sustained expression of Rpe65 in the retinal pigment epithelium.
      Electroretinogram recordings showed that Rpe65 gene transfer restored retinal
      function to a near-normal pattern. We performed histological analyses using cone
      specific markers and demonstrated that Rpe65 gene transfer completely prevented
      cone degeneration until at least four months, an age at which almost all cones
      have degenerated in the untreated Rpe65-deficient mouse. We established an
      algorithm that allows prediction of the cone-rescue area as a function of
      transgene expression, which should be a useful tool for future clinical trials.
      Finally, in mice deficient for both RPE65 and rod transducin, Rpe65 gene transfer
      restored cone function when applied at an early stage of the disease.
      CONCLUSIONS: By demonstrating that lentivirus-mediated Rpe65 gene transfer
      protects and restores the function of cones in the Rpe65(-/-) mouse, this study
      reinforces the therapeutic value of gene therapy for RPE65 deficiencies, suggests
      a cone-preserving treatment for the retina, and evaluates a potentially effective
      viral vector for this purpose.

PMID- 17032059
TI  - Cost-effectiveness study of three antimalarial drug combinations in Tanzania.
AB  - BACKGROUND: As a result of rising levels of drug resistance to conventional
      monotherapy, the World Health Organization (WHO) and other international
      organisations have recommended that malaria endemic countries move to combination
      therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major
      barrier to deployment. There is little evidence from field trials on the cost
      effectiveness of these new combinations. METHODS AND FINDINGS: An economic
      evaluation of drug combinations was designed around a randomised effectiveness
      trial of combinations recommended by the WHO, used to treat Tanzanian children
      with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ),
      AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and
      artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in
      terms of resource savings and cases of malaria averted (based on parasitological
      failure rates at days 14 and 28). All costs to providers and to patients and
      their families were estimated and uncertain variables were subjected to
      univariate sensitivity analysis. Incremental analysis comparing each combination
      to monotherapy (AQ) revealed that from a societal perspective AL was most cost
      effective at day 14. At day 28 the difference between AL and AQ+AS was
      negligible; both resulted in a gross savings of approximately US1.70 dollars or a
      net saving of US22.40 dollars per case averted. Varying the accuracy of diagnosis
      and the subsistence wage rate used to value unpaid work had a significant effect
      on the number of cases averted and on programme costs, respectively, but this did
      not change the finding that AL and AQ+AS dominate monotherapy. CONCLUSIONS: In an
      area of high drug resistance, there is evidence that AL and AQ+AS are the most
      cost-effective drugs despite being the most expensive, because they are
      significantly more effective than other options and therefore reduce the need for
      further treatment. This is not necessarily the case in parts of Africa where
      recrudescence following SP and AQ treatment (and their combination) is lower so
      that the relative advantage of ACTs is smaller, or where diagnostic services are
      not accurate and as a result much of the drug goes to those who do not have
      malaria.

PMID- 17032060
TI  - A population-based study on alcohol and high-risk sexual behaviors in Botswana.
AB  - BACKGROUND: In Botswana, an estimated 24% of adults ages 15-49 years are infected
      with HIV. While alcohol use is strongly associated with HIV infection in Africa,
      few population-based studies have characterized the association of alcohol use
      with specific high-risk sexual behaviors. METHODS AND FINDINGS: We conducted a
      cross-sectional, population-based study of 1,268 adults from five districts in
      Botswana using a stratified two-stage probability sample design. Multivariate
      logistic regression was used to assess correlates of heavy alcohol consumption
      (>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable.
      We also assessed gender-specific associations between alcohol use as a primary
      independent variable (categorized as none, moderate, problem and heavy drinking)
      and several risky sex outcomes including: (a) having unprotected sex with a
      nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or
      selling sex in exchange for money or other resources. Criteria for heavy drinking
      were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use
      included male gender, intergenerational relationships (age gap > or =10 y),
      higher education, and living with a sexual partner. Among men, heavy alcohol use
      was associated with higher odds of all risky sex outcomes examined, including
      unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32),
      multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR =
      3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption
      was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to
      6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR
      = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between
      alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than
      both problem and heavy drinkers. CONCLUSIONS: Alcohol use is associated with
      multiple risks for HIV transmission among both men and women. The findings of
      this study underscore the need to integrate alcohol abuse and HIV prevention
      efforts in Botswana and elsewhere.

PMID- 17032061
TI  - Responding to AIDS, tuberculosis, malaria, and emerging infectious diseases in
      Burma: dilemmas of policy and practice.

PMID- 17032062
TI  - HIV-1 viral load assays for resource-limited settings.

PMID- 17032063
TI  - Asymmetrical reinforcement and Wolbachia infection in Drosophila.
AB  - Reinforcement refers to the evolution of increased mating discrimination against
      heterospecific individuals in zones of geographic overlap and can be considered a
      final stage in the speciation process. One the factors that may affect
      reinforcement is the degree to which hybrid matings result in the permanent loss
      of genes from a species' gene pool. Matings between females of Drosophila
      subquinaria and males of D. recens result in high levels of offspring mortality,
      due to interspecific cytoplasmic incompatibility caused by Wolbachia infection of
      D. recens. Such hybrid inviability is not manifested in matings between D. recens
      females and D. subquinaria males. Here we ask whether the asymmetrical hybrid
      inviability is associated with a corresponding asymmetry in the level of
      reinforcement. The geographic ranges of D. recens and D. subquinaria were found
      to overlap across a broad belt of boreal forest in central Canada. Females of D.
      subquinaria from the zone of sympatry exhibit much stronger levels of
      discrimination against males of D. recens than do females from allopatric
      populations. In contrast, such reproductive character displacement is not evident
      in D. recens, consistent with the expected effects of unidirectional cytoplasmic
      incompatibility. Furthermore, there is substantial behavioral isolation within D.
      subquinaria, because females from populations sympatric with D. recens
      discriminate against allopatric conspecific males, whereas females from
      populations allopatric with D. recens show no discrimination against any
      conspecific males. Patterns of general genetic differentiation among populations
      are not consistent with patterns of behavioral discrimination, which suggests
      that the behavioral isolation within D. subquinaria results from selection
      against mating with Wolbachia-infected D. recens. Interspecific cytoplasmic
      incompatibility may contribute not only to post-mating isolation, an effect
      already widely recognized, but also to reinforcement, particularly in the
      uninfected species. The resulting reproductive character displacement not only
      increases behavioral isolation from the Wolbachia-infected species, but may also
      lead to behavioral isolation between populations of the uninfected species. Given
      the widespread occurrence of Wolbachia among insects, it thus appears that there
      are multiple ways by which these endosymbionts may directly and indirectly
      contribute to reproductive isolation and speciation.

PMID- 17032064
TI  - CDPKs CPK6 and CPK3 function in ABA regulation of guard cell S-type anion- and
      Ca(2+)-permeable channels and stomatal closure.
AB  - Abscisic acid (ABA) signal transduction has been proposed to utilize cytosolic
      Ca(2+) in guard cell ion channel regulation. However, genetic mutants in Ca(2+)
      sensors that impair guard cell or plant ion channel signaling responses have not
      been identified, and whether Ca(2+)-independent ABA signaling mechanisms suffice
      for a full response remains unclear. Calcium-dependent protein kinases (CDPKs)
      have been proposed to contribute to central signal transduction responses in
      plants. However, no Arabidopsis CDPK gene disruption mutant phenotype has been
      reported to date, likely due to overlapping redundancies in CDPKs. Two
      Arabidopsis guard cell-expressed CDPK genes, CPK3 and CPK6, showed gene
      disruption phenotypes. ABA and Ca(2+) activation of slow-type anion channels and,
      interestingly, ABA activation of plasma membrane Ca(2+)-permeable channels were
      impaired in independent alleles of single and double cpk3cpk6 mutant guard cells.
      Furthermore, ABA- and Ca(2+)-induced stomatal closing were partially impaired in
      these cpk3cpk6 mutant alleles. However, rapid-type anion channel current activity
      was not affected, consistent with the partial stomatal closing response in double
      mutants via a proposed branched signaling network. Imposed Ca(2+) oscillation
      experiments revealed that Ca(2+)-reactive stomatal closure was reduced in CDPK
      double mutant plants. However, long-lasting Ca(2+)-programmed stomatal closure
      was not impaired, providing genetic evidence for a functional separation of these
      two modes of Ca(2+)-induced stomatal closing. Our findings show important
      functions of the CPK6 and CPK3 CDPKs in guard cell ion channel regulation and
      provide genetic evidence for calcium sensors that transduce stomatal ABA
      signaling.

PMID- 17032065
TI  - Strict host-symbiont cospeciation and reductive genome evolution in insect gut
      bacteria.
AB  - Host-symbiont cospeciation and reductive genome evolution have been identified in
      obligate endocellular insect symbionts, but no such example has been identified
      from extracellular ones. Here we first report such a case in stinkbugs of the
      family Plataspidae, wherein a specific gut bacterium is vertically transmitted
      via "symbiont capsule." In all of the plataspid species, females produced
      symbiont capsules upon oviposition and their gut exhibited specialized traits for
      capsule production. Phylogenetic analysis showed that the plataspid symbionts
      constituted a distinct group in the gamma-Proteobacteria, whose sister group was
      the aphid obligate endocellular symbionts Buchnera. Removal of the symbionts
      resulted in retarded growth, mortality, and sterility of the insects. The host
      phylogeny perfectly agreed with the symbiont phylogeny, indicating strict host
      symbiont cospeciation despite the extracellular association. The symbionts
      exhibited AT-biased nucleotide composition, accelerated molecular evolution, and
      reduced genome size, as has been observed in obligate endocellular insect
      symbionts. These findings suggest that not the endocellular conditions themselves
      but the population genetic attributes of the vertically transmitted symbionts are
      probably responsible for the peculiar genetic traits of these insect symbionts.
      We proposed the designation "Candidatus Ishikawaella capsulata" for the plataspid
      symbionts. The plataspid stinkbugs, wherein the host-symbiont associations can be
      easily manipulated, provide a novel system that enables experimental approaches
      to previously untouched aspects of the insect-microbe mutualism. Furthermore,
      comparative analyses of the sister groups, the endocellular Buchnera and the
      extracellular Ishikawaella, would lead to insights into how the different
      symbiotic lifestyles have affected their genomic evolution.

PMID- 17032066
TI  - A signaling network for patterning of neuronal connectivity in the Drosophila
      brain.
AB  - The precise number and pattern of axonal connections generated during brain
      development regulates animal behavior. Therefore, understanding how developmental
      signals interact to regulate axonal extension and retraction to achieve precise
      neuronal connectivity is a fundamental goal of neurobiology. We investigated this
      question in the developing adult brain of Drosophila and find that it is
      regulated by crosstalk between Wnt, fibroblast growth factor (FGF) receptor, and
      Jun N-terminal kinase (JNK) signaling, but independent of neuronal activity. The
      Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a
      Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK
      activity. JNK activity is necessary and sufficient for axon extension, whereas
      the antagonistic Wnt and FGF signals act to balance the extension and retraction
      required for the generation of the precise wiring pattern.

PMID- 17032067
TI  - The end of the end of ideology.
AB  - The "end of ideology" was declared by social scientists in the aftermath of World
      War II. They argued that (a) ordinary citizens' political attitudes lack the kind
      of stability, consistency, and constraint that ideology requires; (b) ideological
      constructs such as liberalism and conservatism lack motivational potency and
      behavioral significance; (c) there are no major differences in content (or
      substance) between liberal and conservative points of view; and (d) there are few
      important differences in psychological processes (or styles) that underlie
      liberal versus conservative orientations. The end-of-ideologists were so
      influential that researchers ignored the topic of ideology for many years.
      However, current political realities, recent data from the American National
      Election Studies, and results from an emerging psychological paradigm provide
      strong grounds for returning to the study of ideology. Studies reveal that there
      are indeed meaningful political and psychological differences that covary with
      ideological self-placement. Situational variables--including system threat and
      mortality salience--and dispositional variables--including openness and
      conscientiousness--affect the degree to which an individual is drawn to liberal
      versus conservative leaders, parties, and opinions. A psychological analysis is
      also useful for understanding the political divide between "red states" and "blue
      states."

PMID- 17032068
TI  - Evidence-based youth psychotherapies versus usual clinical care: a meta-analysis
      of direct comparisons.
AB  - In the debate over evidence-based treatments (EBTs) for youth, one question is
      central: Do EBTs produce better outcomes than the usual interventions employed in
      clinical care? The authors addressed this question through a meta-analysis of 32
      randomized trials that directly compared EBTs with usual care. EBTs outperformed
      usual care. Effects fell within the small to medium range at posttreatment,
      increasing somewhat at follow-up. EBT superiority was not reduced by high levels
      of youth severity or by inclusion of minority youths. The findings underscore a
      need for improved study designs and detailed treatment descriptions. In the
      future, the EBT versus usual care genre can inform the search for the most
      effective interventions and guide treatment selection in clinical care.

PMID- 17032069
TI  - Mental balance and well-being: building bridges between Buddhism and Western
      psychology.
AB  - Clinical psychology has focused primarily on the diagnosis and treatment of
      mental disease, and only recently has scientific attention turned to
      understanding and cultivating positive mental health. The Buddhist tradition, on
      the other hand, has focused for over 2,500 years on cultivating exceptional
      states of mental well-being as well as identifying and treating psychological
      problems. This article attempts to draw on centuries of Buddhist experiential and
      theoretical inquiry as well as current Western experimental research to highlight
      specific themes that are particularly relevant to exploring the nature of mental
      health. Specifically, the authors discuss the nature of mental well-being and
      then present an innovative model of how to attain such well-being through the
      cultivation of four types of mental balance: conative, attentional, cognitive,
      and affective.

PMID- 17032070
TI  - The psychotherapy adaptation and modification framework: application to Asian
      Americans.
AB  - Although effective treatments for many mental disorders have been developed,
      little research has been conducted to determine whether these interventions are
      effective in treating those from diverse backgrounds. Recent reports have
      suggested that ethnic minorities are less likely to receive quality health
      services and that they evidence worse treatment outcomes when compared with other
      groups. To improve care for those from diverse backgrounds, Western-developed
      psychotherapies may need to be culturally modified or adapted to become more
      effective in treating ethnic minorities. This article addresses the need for
      adapting psychotherapy and provides a conceptual framework for making such
      modifications. The psychotherapy adaptation and modification framework model is
      applied to recent Asian American immigrants as an illustrative example. However,
      it may also serve as a point of departure to adapt therapies for other
      ethnocultural groups.

PMID- 17032078
TI  - Cognitive sex differences and mathematics and science achievement.

PMID- 17032079
TI  - There is more to aptitude than cognitive capacities.

PMID- 17032080
TI  - Cognitive styles partly explain gender disparity in engineering.

PMID- 17032083
TI  - On the cover.

PMID- 17032082
TI  - The poor availability of psychological research data for reanalysis.

PMID- 17032084
TI  - Introduction to the special section: growth following highly stressful life
      events--current status and future directions.
AB  - Interest in the phenomenon of perceived growth following highly stressful
      experiences continues to proliferate. Already there is abundant evidence that
      perceptions of growth are commonly reported, often by the majority of people
      experiencing even the most traumatic of events. However, much remains to be
      learned about perceptions of growth. In this article, the authors pose 7 major
      theoretical and empirical questions regarding perceived growth, including issues
      of measurement, validity, mechanisms, links with well-being, and clinical
      implications. The authors summarize the current status of psychologists'
      knowledge, including articles in the present special section, and conclude that
      there is much to learn about perceived growth. The authors end with suggestions
      for future research.

PMID- 17032085
TI  - A meta-analytic review of benefit finding and growth.
AB  - The authors conducted a meta-analysis to examine the relations of benefit finding
      to psychological and physical health as well as to a specific set of demographic,
      stressor, personality, and coping correlates. Results from 87 cross-sectional
      studies reported in 77 articles showed that benefit finding was related to less
      depression and more positive well-being but also more intrusive and avoidant
      thoughts about the stressor. Benefit finding was unrelated to anxiety, global
      distress, quality of life, and subjective reports of physical health. Moderator
      analyses showed that relations of benefit finding to outcomes were affected by
      the amount of time that had passed since stressor onset, the benefit finding
      measured used, and the racial composition of the sample.

PMID- 17032086
TI  - Posttraumatic growth and HIV disease progression.
AB  - The relationship between posttraumatic growth (PTG; perceiving positive changes
      since diagnosis) and disease status, determined by changes in viral load and CD4
      count over time, was examined among 412 people living with HIV. In controlled
      multiple regression models, PTG was not associated with disease status over time
      for the entire sample. However, there were significant associations for certain
      subgroups. PTG was positively associated with CD4 counts for Hispanic
      participants (vs. non-Hispanic) and those with low (vs. high) levels of optimism.
      PTG was inversely associated with viral load among those low (vs. high) in
      pessimism. Although PTG was inversely associated with depressive symptoms,
      alcohol, and illicit drug use, these factors did not account for the findings.

PMID- 17032087
TI  - Curvilinear associations between benefit finding and psychosocial adjustment to
      breast cancer.
AB  - Two previously studied cohorts of women with nonmetastatic breast cancer (Ns =
      230 and 136) were reexamined. Participants were assessed during the year after
      surgery and 5-8 years later. Associations were examined between benefit finding
      (BF) and several indicators of psychosocial adjustment (e.g., perceived quality
      of life, positive affect, negative affect, social disruption, and intrusive
      thoughts). Significant curvilinear relations between BF and other outcomes were
      observed cross-sectionally during initial assessment and at long-term follow-up
      in both samples. Compared with the intermediate BF group, low and high BF groups
      had better psychosocial adjustment. Further analyses indicated that the high BF
      group reported higher optimism and more use of positive reframing and religious
      coping than the other BF groups. Discussion highlights the need to examine
      nonlinear as well as linear relationships.

PMID- 17032088
TI  - Urban teens: Trauma, posttraumatic growth, and emotional distress among female
      adolescents.
AB  - Urban teens face many traumas, with implications for potential growth and
      distress. This study examined traumatic events, posttraumatic growth, and
      emotional distress over 18 months among urban adolescent girls (N = 328).
      Objectives were to (a) describe types of traumatic events, (b) determine how type
      and timing of events relate to profiles of posttraumatic growth, and (c)
      prospectively examine effects of event type and posttraumatic growth on short-
      and long-term emotional distress with controls for pre-event distress. Results
      indicate that type of event was related to profiles of posttraumatic growth, but
      not with subsequent emotional distress. When baseline emotional distress was
      controlled, posttraumatic growth was associated with subsequent reductions in
      short- and long-term emotional distress. Implications for future research and
      clinical practice with adolescents are addressed.

PMID- 17032089
TI  - The assessment and validity of stress-related growth in a community-based sample.
AB  - In an investigation of the assessment and construct validity of stress-related
      growth, community-dwelling women (N = 163) wrote essays about the impact of a
      stressful life event that had occurred in the previous few years and completed
      the Posttraumatic Growth Inventory (PTGI). Independent ratings of growth in the
      essays were positively correlated with PTGI scores, suggesting that endorsement
      of growth on questionnaires can be substantiated by personal accounts. There was
      no relation between reports of growth on the PTGI and socially desirable
      responding or negative mood. Higher PTGI scores were associated with greater
      positive mood and greater depth of processing in the essays. These findings
      support the validity of stress-related growth as a construct and its assessment
      via questionnaire.

PMID- 17032090
TI  - Assessing the validity of self-reported stress-related growth.
AB  - The purpose of these studies was to assess the validity of self-reported stress
      related growth (SRG). In Study 1, individuals with breast cancer (n = 70)
      generally did not report greater well-being than a matched comparison group (n =
      70). In Study 2, there were no significant differences in well-being between
      undergraduate students who said that something positive had come out of their
      worst stressor (n = 34) and those who reported no positives (n = 34). In Study 3,
      specific domains of SRG assessed in undergraduate students (n = 96) generally
      were not uniquely related to corresponding well-being measures. Thus, the authors
      found fairly little evidence for the validity of self-reported SRG. Future
      research directions are highlighted.

PMID- 17032091
TI  - Perception of benefits and costs during SARS outbreak: An 18-month prospective
      study.
AB  - In this study, the authors examined perceived benefits and costs of the outbreak
      of severe acute respiratory syndrome (SARS). Mixed accounts of benefits and
      costs, rather than exclusive accounts of only benefits or costs, were proposed to
      be characterized by nondefensiveness and enduring changes in psychosocial
      resources. Participants were 70 SARS recoverers, 59 family members of SARS
      recoverers, and 172 healthy adults residing in Hong Kong--a SARS-affected region.
      Results show that participants giving an exclusive account of benefits had higher
      levels of defensiveness than those giving a mixed account and those giving an
      exclusive account of costs. Only the perceived impact of benefits given in mixed
      accounts were related to future accruements in personal and social resources over
      an 18-month period.

PMID- 17032092
TI  - Neural correlates of posttraumatic growth after severe motor vehicle accidents.
AB  - Frontal brain asymmetry has been associated with emotion- and motivation-related
      constructs. The authors examined the relationship between frontal brain asymmetry
      and subjective perception of posttraumatic growth (PTG) after severe motor
      vehicle accidents (MVAs). Eighty-two survivors of MVAs completed self-report
      measures of PTG, trait and state affect, and diagnostic interviews assessing
      clinical status, and underwent measurement of resting electroencephalographic
      activity. As predicted, increased relative left frontal activation was
      significantly related to PTG, even when statistically controlling for
      dispositional positive affect. The authors assume that approach-related
      motivational tendencies associated with higher relative left frontal brain
      activity may be involved in the process and outcome of PTG.

PMID- 17032093
TI  - Writing about the benefits of an interpersonal transgression facilitates
      forgiveness.
AB  - The authors examined the effects of writing about the benefits of an
      interpersonal transgression on forgiveness. Participants (N = 304) were randomly
      assigned to one of three 20-min writing tasks in which they wrote about either
      (a) traumatic features of the most recent interpersonal transgression they had
      suffered, (b) personal benefits resulting from the transgression, or (c) a
      control topic that was unrelated to the transgression. Participants in the
      benefit-finding condition became more forgiving toward their transgressors than
      did those in the other 2 conditions, who did not differ from each other. In part,
      the benefit-finding condition appeared to facilitate forgiveness by encouraging
      participants to engage in cognitive processing as they wrote their essays.
      Results suggest that benefit finding may be a unique and useful addition to
      efforts to help people forgive interpersonal transgressions through structured
      interventions. The Transgression-Related Interpersonal Motivations Inventory--18
      Item Version (TRIM-18) is appended.

PMID- 17032094
TI  - Cognitive processing therapy for veterans with military-related posttraumatic
      stress disorder.
AB  - Sixty veterans (54 men, 6 women) with chronic military-related posttraumatic
      stress disorder (PTSD) participated in a wait-list controlled trial of cognitive
      processing therapy (CPT). The overall dropout rate was 16.6% (20% from CPT, 13%
      from waiting list). Random regression analyses of the intention-to-treat sample
      revealed significant improvements in PTSD and comorbid symptoms in the CPT
      condition compared with the wait-list condition. Forty percent of the intention
      to-treat sample receiving CPT did not meet criteria for a PTSD diagnosis, and 50%
      had a reliable change in their PTSD symptoms at posttreatment assessment. There
      was no relationship between PTSD disability status and outcomes. This trial
      provides some of the most encouraging results of PTSD treatment for veterans with
      chronic PTSD and supports increased use of cognitive- behavioral treatments in
      this population.

PMID- 17032095
TI  - Benzodiazepine discontinuation among adults with GAD: A randomized trial of
      cognitive-behavioral therapy.
AB  - This study evaluated the specific effectiveness of cognitive-behavior therapy
      (CBT) combined with medication tapering for benzodiazepine discontinuation among
      generalized anxiety disorder (GAD) patients by using a nonspecific therapy
      control group. Sixty-one patients who had used benzodiazepines for more than 12
      months were randomly assigned to the experimental conditions. Nearly 75% of
      patients in the CBT condition completely ceased benzodiazepine intake, as
      compared with 37% in the control condition. Results of the 3-, 6-, and 12-month
      follow-ups confirmed the maintenance of complete cessation. Discontinuation rates
      remained twice as high in the CBT condition. The number of patients who no longer
      met GAD criteria was also greater in the CBT condition. The addition of specific
      CBT components thus seemed to facilitate benzodiazepine tapering among patients
      with GAD.

PMID- 17032096
TI  - The effects of forgiveness therapy on depression, anxiety, and posttraumatic
      stress for women after spousal emotional abuse.
AB  - Emotionally abused women experience negative psychological outcomes long after
      the abusive spousal relationship has ended. This study compares forgiveness
      therapy (FT) with an alternative treatment (AT; anger validation, assertiveness,
      interpersonal skill building) for emotionally abused women who had been
      permanently separated for 2 or more years (M = 5.00 years, SD = 2.61; n = 10 per
      group). Participants, who were matched, yoked, and randomized to treatment group,
      met individually with the intervener. Mean intervention time was 7.95 months (SD
      = 2.61). The relative efficacy of FT and AT was assessed at p < .05. Participants
      in FT experienced significantly greater improvement than AT participants in
      depression, trait anxiety, posttraumatic stress symptoms, self-esteem,
      forgiveness, environmental mastery, and finding meaning in suffering, with gains
      maintained at follow-up (M = 8.35 months, SD = 1.53). FT has implications for the
      long-term recovery of postrelationship emotionally abused women.

PMID- 17032097
TI  - The relationship of perfectionism, depression, and therapeutic alliance during
      treatment for depression: latent difference score analysis.
AB  - The authors examined the longitudinal relationship of patient-rated
      perfectionism, clinician-rated depression, and observer-rated therapeutic
      alliance using the latent difference score (LDS) analytic framework. Outpatients
      involved in the Treatment for Depression Collaborative Research Program completed
      measures of perfectionism and depression at 5 occasions throughout treatment,
      with therapeutic alliance measured early in therapy. First, LDS analyses of
      perfectionism and depression established longitudinal change models. Further LDS
      analyses revealed significant longitudinal interrelationships, in which
      perfectionism predicted the subsequent rate of depression change, consistent with
      a personality vulnerability model of depression. In the final LDS model, the
      strength of the therapeutic alliance significantly predicted longitudinal
      perfectionism change, and perfectionism significantly predicted the rate of
      depression change throughout therapy. These results clarify the patterns of
      growth and change for these indicators throughout depression treatment,
      demonstrating an alternative method for evaluating longitudinal dynamics in
      therapy.

PMID- 17032098
TI  - Brief motivational interventions for heavy college drinkers: A randomized
      controlled trial.
AB  - In this randomized controlled trial, the authors evaluated brief motivational
      interventions (BMIs) for at-risk college drinkers. Heavy drinking students (N =
      509; 65% women, 35% men) were randomized into 1 of 6 intervention conditions
      formed by crossing the baseline Timeline Followback (TLFB) interview (present
      versus absent) and intervention type (basic BMI, BMI enhanced with a decisional
      balance module, or none). Assessments completed at baseline, 1, 6, and 12 months
      measured typical and risky drinking as well as drinking-related problems.
      Relative to controls, the TLFB interview reduced consumption but not problems at
      1 month. The basic BMI improved all drinking outcomes beyond the effects of the
      TLFB interview at 1 month, whereas the enhanced BMI did not. Risk reduction
      achieved by brief interventions maintained throughout the follow-up year.

PMID- 17032100
TI  - Psychiatric symptoms and community violence among high-risk patients: A test of
      the relationship at the weekly level.
AB  - Given the availability of violence risk assessment tools, clinicians are now
      better able to identify high-risk patients. Once these patients have been
      identified, clinicians must monitor risk state and intervene when necessary to
      prevent harm. Clinical practice is dominated by the assumption that increases in
      psychiatric symptoms elevate risk of imminent violence. This intensive study of
      patients (N = 132) at high risk for community violence is the first to evaluate
      prospectively the temporal relation between symptoms and violence. Symptoms were
      assessed with the Brief Symptom Inventory and threat/control override (TCO)
      scales. Results indicate that a high-risk patient with increased anger in 1 week
      is significantly more likely to be involved in serious violence in the following
      week. This was not true of other symptom constellations (anxiety, depression,
      TCO) or general psychological distress. The authors found no evidence that
      increases in the latter symptoms during 1 week provide an independent foundation
      for expecting violence during the following week.

PMID- 17032099
TI  - The use of contingency management and motivational/skills-building therapy to
      treat young adults with marijuana dependence.
AB  - Marijuana-dependent young adults (N = 136), all referred by the criminal justice
      system, were randomized to 1 of 4 treatment conditions: a motivational/skills
      building intervention (motivational enhancement therapy/cognitive-behavioral
      therapy; MET/CBT) plus incentives contingent on session attendance or submission
      of marijuana-free urine specimens (contingency management; CM), MET/CBT without
      CM, individual drug counseling (DC) plus CM, and DC without CM. There was a
      significant main effect of CM on treatment retention and marijuana-free urine
      specimens. Moreover, the combination of MET/CBT plus CM was significantly more
      effective than MET/CBT without CM or DC plus CM, which were in turn more
      effective than DC without CM for treatment attendance and percentage of marijuana
      free urine specimens. Participants assigned to MET/CBT continued to reduce the
      frequency of their marijuana use through a 6-month follow-up.

PMID- 17032101
TI  - Cognitive adaptation theory and breast cancer recurrence: Are there limits?
AB  - Relations of the components of cognitive adaptation theory (self-esteem,
      optimism, control) to quality of life and benefit finding were examined for 70
      women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5
      years ago. Half of these women experienced a recurrence within the 5 years; the
      other half remained disease free. Women were matched on age, race, stage of
      disease, and intervention condition. Baseline perceptions of personal control
      over illness, but not general self-esteem or optimism, were associated with
      women's reports of worse physical functioning, worse mental functioning, and less
      benefit finding 5 years later for recurrent women but not disease-free women.
      These findings highlight the notion that there may be boundary conditions on the
      adaptiveness of perceived control.

PMID- 17032102
TI  - Temporary anchorage devices for tooth movement: a review and case reports.
AB  - BACKGROUND: Temporary anchorage devices (TADs) are immediately loaded miniscrews
      and osseointegrated palatal implants that are placed to control tooth movement
      during orthodontic treatment and removed when the treatment is completed. They
      are a relatively new addition to the dental armamentarium and can be used in some
      cases to replace traditional orthodontic extraoral appliances. Because placement
      requires a surgical procedure, orthodontists often refer patients to
      periodontists for this stage of the overall treatment plan. METHODS: The purpose
      of this article is to introduce TADs to the periodontal community by reviewing
      their purpose, various systems that are available, indications for use, site
      selection, and surgical technique. Case reports are included to illustrate this
      new treatment approach. RESULTS: Placement of osseointegrated implants for
      restorative purposes is an established procedure in most periodontal offices.
      Although placement of TADs is a modification of these familiar techniques, most
      of these devices serve a very different purpose, involving new loading protocols
      with no expectation of osseointegration in patients usually not receiving
      concomitant periodontal therapy. CONCLUSIONS: Periodontists' knowledge of soft
      and hard tissue anatomy and their ability to manage soft tissue position them
      well to collaborate with orthodontists in this multidisciplinary treatment.
      However, as with every new modality, clinicians need to understand the specific
      uses and limitations of TADs and work closely with their referring orthodontists
      in identifying patients for whom miniscrew implants are a viable option.
      Periodontal practices are based primarily on referrals from dental colleagues,
      and the concept of periodontists working cooperatively with orthodontists is not
      new. Including TAD placement among the services periodontists offer provides
      another opportunity to further this relationship and to establish periodontists
      as appropriate resources for this segment of orthodontic treatment.

PMID- 17032103
TI  - Flap thickness as a predictor of root coverage: a systematic review.
AB  - BACKGROUND: Thick gingival tissue eases manipulation, maintains vascularity, and
      promotes wound healing during and after surgery. A few recent case reports
      correlate greater flap thickness to mean and complete root coverage after
      mucogingival therapy for recession defects. The aim of this systematic review is
      to appraise the current literature on this subject and to combine existing data
      to verify the presence of any association between gingival thickness and root
      coverage outcomes. METHODS: Human studies that reported the number and class of
      recessions, measured flap thickness at a well-defined location, described the
      method of root coverage used, followed results for at least 3 months, and
      detailed mean root coverage underwent review and statistical analysis.
      Investigations were scored from 1 to 5 based on methodological quality. Weighted
      gingival thickness and weighted mean root coverage was calculated based on
      standard error. Statistical analysis used the Mann-Whitney test, analysis of
      variance (ANOVA), and linear regression to determine any correlation between a
      number of factors (i.e., thickness, treatment type, and follow-up time) and mean
      and complete root coverage. A significant P value was set at <0.05. RESULTS:
      Fifteen investigations met the inclusion criteria. All of these reported at least
      0.7 mm of flap thickness, although measurement locations varied. Treatment
      modalities included coronally advanced flap, connective tissue graft, and guided
      tissue regeneration with and without adjuncts. A significant moderate correlation
      occurred between weighted flap thickness and weighted mean root coverage and
      weighted complete root coverage (r = 0.646 and 0.454, respectively). According to
      Mann-Whitney analysis, a critical threshold thickness >1.1 mm existed for
      weighted mean and complete root coverage (P <0.02). The type of treatment
      rendered also influenced root coverage. Further simple linear regression revealed
      a high correlation between weighted thickness and weighted mean root coverage in
      connective tissue grafting and guided tissue regeneration (r = 0.909 and 0.714,
      respectively) but not coronally advanced flap therapy. Study score and follow-up
      time did not affect the percentage of root coverage. CONCLUSION: Within the
      limits of this review, a positive association exists between weighted flap
      thickness and mean and complete root coverage.

PMID- 17032104
TI  - Effect of periodontal treatment on serum C-reactive protein levels: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Systemic inflammation is increasingly being recognized as a risk
      factor for adverse cardiovascular events. Evidence is accumulating that
      associates periodontal disease with a higher risk for atherosclerotic plaque
      formation. A positive association between circulating C-reactive protein (CRP)
      levels and periodontal disease may be responsible for these observations. We
      undertook a systematic review and conducted a meta-analysis of the available
      evidence to examine the effect of periodontal treatment on systemic CRP levels
      and to assess the quality of the available evidence. METHODS: We conducted a
      systematic search of the English-language literature on the effect of periodontal
      treatment on CRP levels, as assessed by high-sensitivity assays, at least 2
      months after periodontal treatment. The search was conducted in MEDLINE between
      1966 and July 2005 and the Cochrane Central Register of Controlled Trials. We
      performed a meta-analysis using the DerSimonian and Laird random-effects model.
      RESULTS: The literature search yielded 814 citations of which 10 met the
      inclusion criteria. The meta-analysis of the randomized controlled trials (RCTs)
      showed that the difference in serum CRP levels is not significantly different
      between the two arms. Similarly, results from the single-cohort studies showed
      that the difference on serum CRP levels was not significantly different before
      and after treatment. CONCLUSIONS: There is now a large body of evidence to
      indicate that systemic inflammation is present in patients with periodontal
      disease. Thus, information from RCTs and single-cohort studies does not support
      the hypothesis that periodontal treatment can reduce systemic CRP levels.

PMID- 17032105
TI  - Gingivitis and periodontitis as antagonistic modulators of gingival perfusion.
AB  - BACKGROUND: We explore the possible association between the extent of gingivitis
      or periodontitis and an index of gingival microvascular perfusion response to
      compression of alveolar mucosa, called the gingival perfusion index (GIPI).
      METHODS: A cross-sectional analytical study was done in a sample of 60 adults,
      including healthy and non-insulin-dependent diabetic subjects of either gender,
      with teeth in the anteromandibular sextant with or without gingivitis and with or
      without periodontitis at the lower-left lateral incisor (LLLI). A sample was
      selected by convenience non-probability sampling. Gingival perfusion was
      evaluated at labial LLLI attached gingiva. Two perfusion recordings were done 5
      minutes apart, each one consisting of a 40-second control phase, a 22-second
      compression phase, and a 40-second postcompression phase. LLLI alveolar mucosa
      was compressed with a wood-mounted cotton swab until reaching about one-fifth of
      the control perfusion value. GIPI was used as response dependent variable. The
      gingival index and probing depth were used as measures of the extent of
      gingivitis and periodontitis, respectively. RESULTS: By analysis of covariance
      and multiple regression analysis, it was found that only the probing depth
      (negatively) and gingival index (positively) predicted GIPI (R(2) adjusted =
      0.5194, P <0.0001). CONCLUSIONS: The data strongly suggest that, at least in the
      studied sample, gingivitis and periodontitis operate as antagonistic modulators
      of gingival perfusion. The major practical implication of our findings is that an
      increase or decrease in this index (GIPI) at a given attached gingiva site could
      indicate, respectively, the clinical predominance of gingivitis or periodontitis
      in such a site.

PMID- 17032106
TI  - The effects of interproximal distance between roots on the existence of
      interdental papillae according to the distance from the contact point to the
      alveolar crest.
AB  - BACKGROUND: This study investigated the existence of interdental papillae at
      certain distances from the contact point to the alveolar crest, depending on the
      interproximal distance between roots. METHODS: A total of 206 papillae from 80
      patients were examined after the inflammation of the papillae had been minimized
      using non-surgical periodontal therapy. The existence of the interdental papillae
      was determined using the following categorization: 1) papillae were deemed to be
      absent if they did not extend all the way up to the contact point between the
      teeth; and 2) papillae were determined to be present if they filled up to the
      entire proximal space. The interproximal distance between roots and the distance
      from the contact point to the alveolar crest were measured when a full-thickness
      flap was used. The number of papillae present interproximally between roots,
      according to the distance from the contact point to the alveolar crest, was
      analyzed using the x2 analysis method, and the linear-by-linear association
      analysis method was used for trend analysis. RESULTS: The number of papillae that
      filled the interproximal space decreased with increasing distance from the
      contact point to the alveolar crest (P <0.05). In addition, the number of
      papillae that filled the interproximal space decreased with increasing
      interproximal distance between roots (P <0.05) and became more prominently
      decreasing with the increasing distance from the contact point to the alveolar
      crest (especially 4, 5, and 6 mm) (P <0.05). CONCLUSION: The results suggest that
      the interproximal distance between roots and the distance between the contact
      point and the alveolar crest have an independent and combined effect on the
      existence of interproximal papillae.

PMID- 17032107
TI  - Experimental intrabony and periodontal defects treated with natural mineral
      combined with a synthetic cell-binding Peptide in the canine: morphometric
      evaluations.
AB  - BACKGROUND: A synthetic peptide (P-15) analog of collagen added to anorganic
      bovine bone mineral (ABM) has recently been used as an enhanced bone graft
      material (ABM/P-15). The objective of this study was to test the contribution of
      ABM/P-15 in a new putty form (PEP) in two experimental membrane-protected
      defects: periodontal and intrabony. Its efficacy as filler biomaterial in guided
      tissue regeneration (GTR) and guided bone regeneration (GBR) procedures was
      evaluated histologically and morphometrically. METHODS: In the maxillary canines,
      a facial mucoperiosteal flap was raised bilaterally in nine dogs. Two circular
      defects, 5 mm in diameter and 2 mm in depth, were made on each side: a
      fenestrated periodontal on the canine root and an intrabony in the alveolar
      diastema, anteriorly. PEP particles filled both defects on one side; the
      contralateral side was blood filled (control). All surgical sites were covered
      with a bioabsorbable membrane. Histologically, at 4 months, tissue blocks were
      made using the cutting/grinding non-decalcification method followed by
      morphometric analysis. In the periodontal fenestration root surface, the linear
      percentage of new cementum (%CEM), area percentage of new bone (%NB), and
      residual biomaterial particles (%PEP) were calculated. These same measurements
      were calculated at the intrabony sites, except cementum. The amount of direct NB
      to PEP contact was measured to assess the osteoconductivity level (OSC). The
      Pearson correlation test was used to evaluate any significant relationship
      between the different measured parameters. RESULTS: In the grafted and non
      grafted fenestration root surface defects, %CEM averaged 59.5% and 73.9% (P
      <0.02), respectively; %NB averaged 36.1% and 31.4%, respectively; and %PEP
      averaged 20.6%. The mean percentage of OSC was 52.4%. In the intrabony grafted
      and non-grafted sites, %NB averaged 50.7% and 60.1%, respectively (P <0.02).
      Residual %PEP averaged 26.1%, and OSC averaged 35.6%. At the intrabony sites,
      higher %NB and lower %OSC were found compared to the fenestration sites (P <0.001
      and P <0.03, respectively). Correlation analysis showed a negative correlation
      between %NB and %PEP at the fenestration defects. In between the two defect
      types, %OSC was significantly correlated (P <0.05). CONCLUSIONS: ABM/P-15 putty
      showed osteoconductive and biocompatible qualities. However, at 4 months in this
      model, no enhanced regeneration was present compared to a higher CEM and NB
      growth detected at non-grafted membrane-protected sites.

PMID- 17032108
TI  - Immunohistochemical study of bone sialoprotein and osteopontin in healthy and
      diseased root surfaces.
AB  - BACKGROUND: Periodontal disease is marked by inflammation and damage to tooth
      supporting tissues. In particular, damage occurs to factors present in cementum
      that are thought to have the ability to influence the regeneration of surrounding
      tissues. Bone sialoprotein and osteopontin are major non-collagenous proteins in
      mineralized connective tissues associated with precementoblast chemo-attraction,
      adhesion to the root surface, and cell differentiation. The purpose of this
      investigation was to determine whether the expression and distribution of bone
      sialoprotein and osteopontin on root surfaces affected by periodontitis are
      altered compared to healthy, non-diseased root surfaces. METHODS: Thirty healthy
      and 30 periodontitis-affected teeth were collected. Following fixation and
      demineralization, specimens were embedded in paraffin, sectioned, and exposed to
      antibodies against bone sialoprotein and osteopontin. Stained sections were
      assessed using light microscopy. RESULTS: Bone sialoprotein was not detected in
      the exposed cementum (absence of overlying periodontal ligament) of diseased
      teeth. In most areas where the periodontal ligament was intact, bone sialoprotein
      was detected for healthy and diseased teeth. For teeth reactive for bone
      sialoprotein, the matrix of the cementum just below the periodontal ligament was
      moderately stained. A similar immunoreactivity pattern for osteopontin was
      observed. CONCLUSIONS: The absence of bone sialoprotein and osteopontin staining
      along exposed cementum surfaces may be due to structural and compositional
      changes in matrix components associated with periodontal disease. This may
      influence the ability for regeneration and new connective tissue attachment onto
      previously diseased root surfaces.

PMID- 17032109
TI  - Gingival crevicular fluid osteopontin levels in periodontal health and disease.
AB  - BACKGROUND: Osteopontin (OPN), a glycosylated phosphoprotein, is a bone matrix
      component produced by osteoblasts, osteoclasts, and macrophages as a
      multifunctional cytokine. OPN anchors osteoclasts to the bone surface, and its
      absence leads to impaired bone resorption. The aim of the present study was to
      assess the relation between clinical parameters and concentrations of OPN within
      gingival crevicular fluid (GCF) from inflamed gingiva and periodontitis sites
      and, subsequently, after the treatment of periodontitis sites. METHODS: A total
      of 45 subjects were divided into the following three groups based on modified
      gingival index (MGI) and Ramfjord periodontal disease index (PDI) scores: healthy
      (group I), gingivitis (group II), and chronic periodontitis (group III). A fourth
      group consisted of 15 subjects from group III, 6 to 8 weeks after treatment
      (i.e., scaling and root planing [SRP]). GCF samples collected from each patient
      were quantified for OPN using the enzymatic immunometric assay. Further, the
      correlation between OPN levels in situ with clinical parameters was analyzed in
      all groups and before and after treatment in periodontitis patients. RESULTS: The
      highest mean OPN concentration in GCF (14.347 microg/ml) was observed in group
      III, and the lowest mean OPN concentration in GCF (2.522 microg/ml) was observed
      in group I. Its levels in group III decreased to 8.419 microg/ml after treatment
      (group IV). Further, GCF OPN levels in all the groups showed a statistically
      significant positive correlation with clinical attachment loss (P <0.05).
      CONCLUSIONS: OPN levels increase in GCF from healthy to periodontitis states, and
      periodontal treatment results in the reduction of OPN levels. The data indicate
      that OPN may play a key role in, and could be considered a biomarker of,
      periodontal disease progression.

PMID- 17032110
TI  - Lack of association between periodontal parameters and preeclampsia.
AB  - BACKGROUND: It was hypothesized that periodontal diseases may increase the risk
      of preeclampsia. To test this hypothesis, this study was conducted to determine
      the association between periodontal parameters and preeclampsia among women in
      the north of Jordan. METHODS: A case-control study was conducted among women who
      gave birth at Princes Badea Teaching Hospital between September 2004 and May
      2005. A total of 115 preeclamptic women and 230 randomly selected controls were
      analyzed. The number of teeth, restorations, decayed tooth surfaces, and clinical
      periodontal parameters were determined within 24 hours after delivery.
      Information regarding participants' demographics, antenatal history, and family
      history were collected through personal interviews. RESULTS: After adjustment for
      potential confounding factors, there were no statistical differences between
      preeclamptic cases and normotensive controls with regard to mean periodontal
      probing depth, mean clinical attachment loss, mean gingival recession, mean
      plaque index, and mean gingival index. In addition, there were no significant
      differences in the percentages of sites with periodontal probing depth >/=3 or
      >/=4 mm, percentages of sites with clinical attachment loss >/=3 mm, number of
      filled surfaces, and number of missing teeth. Only the number of decayed surfaces
      was found to be associated with increased odds of preeclampsia (adjusted odds
      ratio of 1.13; 95% confidence interval of 1.02 and 1.25). CONCLUSION: This study
      did not support the hypothesis of an association between periodontal parameters
      and preeclampsia.

PMID- 17032111
TI  - Porcine enamel protein fractions contain transforming growth factor-beta1.
AB  - BACKGROUND: Enamel extracts are biologically active and capable of inducing
      osteogenesis and cementogenesis, but the specific molecules carrying these
      activities have not been ascertained. The purpose of this study was to identify
      osteogenic factors in porcine enamel extracts. METHODS: Enamel proteins were
      separated by size-exclusion chromatography into four fractions, which were tested
      for their osteogenic activity on osteoblast-like cells (ST2) and human
      periodontal ligament (HPDL) cells. RESULTS: Fraction 3 (Fr.3) and a transforming
      growth factor-beta 1 (TGF-beta1) control reduced alkaline phosphatase (ALP)
      activity in ST2 but enhanced ALP activity in HPDL cells. The enhanced ALP
      activity was blocked by anti-TGF-beta antibodies. Furthermore, using a dual
      luciferase reporter assay, we demonstrated that Fr.3 can induce the promoter
      activity of the plasminogen activator inhibitor type 1 (PAI-1) gene. CONCLUSION:
      These results show that the osteoinductive activity of enamel extracts on HPDL
      cells is mediated by TGF-beta1.

PMID- 17032112
TI  - Changes in periodontal and rheumatological conditions after 2 years in patients
      with juvenile idiopathic arthritis.
AB  - BACKGROUND: The aim of this study was to monitor changes in periodontal
      inflammation in patients with juvenile idiopathic arthritis (JIA) for 2 years. We
      investigated the influence of rheumatic disease activity and antirheumatic
      medication on clinical and immunological parameters of periodontal inflammation
      in these individuals. METHODS: Two years after a baseline examination, the
      periodontal and rheumatological conditions of 18 adolescents with JIA and 14
      control subjects were described. The clinical periodontal inflammation was
      monitored by registration of visual plaque, marginal bleeding, probing depth, and
      clinical attachment loss (AL). Periodontal inflammation was also assessed by
      analysis of the cytokines interleukin (IL)-1beta and IL-18 and the collagenase
      matrix metalloproteinase (MMP)-8 by enzyme-linked immunosorbent assay. RESULTS:
      The erythrocyte sedimentation rate and clinical rheumatological parameters were
      significantly improved at the 2-year follow-up. The number of sites with plaque
      decreased, and the number of pockets >/=4 mm increased, whereas bleeding levels
      and the extension of AL remained unchanged. IL-1beta in gingival crevicular fluid
      decreased significantly in the JIA group after 2 years. No differences were
      observed for IL-1beta, MMP-8, or IL-18 levels between groups after 2 years.
      CONCLUSION: Two years after the baseline examination, no clinical or laboratory
      differences in periodontal inflammation could be found between JIA patients and
      control subjects.

PMID- 17032113
TI  - The effects of loading time on osseointegration and new bone formation around
      dental implants: a histologic and histomorphometric study in dogs.
AB  - BACKGROUND: Immediate loading of dental implants has been introduced as a method
      of reducing implant treatment time without compromising its prognosis. In this
      research, the effects of loading time on the amount of bone-to-implant contact
      and bone formation around dental implants were evaluated histologically. METHODS:
      Three months prior to implantation, the lower premolar teeth of 15 dogs were
      extracted. Three or four dental implants were placed in the healed extraction
      sites for each dog (N = 48). Dividing the dogs into three groups, the implants
      were either loaded 48 hours or 1 week later with metallic or prefabricated
      acrylic crowns or were left unloaded until the time of sacrifice. Three months
      after implant insertion, the animals were sacrificed and samples were
      investigated to define the amount of bone-to-implant contact, lamellar and woven
      bone percentage, and local inflammation of the newly formed bone. RESULTS: No
      significant difference in the observed criteria was reported among the three
      groups (P >0.05); however, the unloaded group had the highest degree of bone-to
      implant contact and the group loaded 48 hours after the primary implant insertion
      had the least. The prosthesis type had no significant effect on the implant
      success rate (P >0.05). The lamellar and woven bone percentage of newly formed
      bone also did not differ in the three groups (P >0.05). One implant from each
      group failed in this study. CONCLUSION: Loading time does not seem to
      significantly affect the degree of osseointegration and bone-to-implant contact
      and the composition of newly formed bone around dental implants.

PMID- 17032114
TI  - Relationship between prereferral periodontal care and periodontal status at time
      of referral.
AB  - BACKGROUND: According to a recent study, the severity of periodontal disease of
      individuals referred for periodontal care is greater now than in 1980.
      Variability in the standard of periodontal care in general dental practices may
      result in less than desirable outcomes and consequences of poorer periodontal
      health. METHODS: A sample of 100 newly referred dental patients from three
      separate periodontal practices in the greater Kansas City, Missouri area
      participated in this study. Data were collected from three sources: 1) a clinical
      chart audit, 2) current periodontal disease status as determined by clinical
      examination, and 3) a patient response questionnaire on past professional care
      and personal oral care habits. Bivariate analyses were performed using a
      statistical package. RESULTS: Of the 100 subjects, 74 were diagnosed as
      periodontal case type IV at the point of referral, of which 29.8% were treatment
      planned by the periodontist for two or more extractions. Teeth treatment planned
      for extraction were significant as a function of disease severity (P = 0.0001).
      Periodontal treatment provided in general dental practices did not vary because
      of disease severity. The incidence of deep cleanings (scaling and root planing)
      was reported slightly higher (32.4%) for case type IV than for case type III
      (26.9%), but this difference was not statistically significant. The average
      number of cleanings received in the general dental office was less than the
      standard of care according to the severity of the disease. CONCLUSION: If one
      assumes that the data obtained in the Kansas City practices are representative of
      a larger geographic area, it indicates that dentistry may be failing to address
      issues of the timely diagnosis of periodontal disease, appropriate treatment,
      and/or timely referral for treatment.

PMID- 17032115
TI  - Histologic evaluation of implants following flapless and flapped surgery: a study
      in canines.
AB  - BACKGROUND: Flapless surgery requires penetration of the alveolar mucosa and bone
      without reflection of mucoperiosteal flaps. Do these techniques force gingival
      tissue or foreign materials into osteotomies? If so, do such tissues or materials
      interfere with osseointegration? A proof-of-principle study using a canine model
      attempted to answer these questions. METHODS: Five young adult Hound Labrador
      mongrel dogs received implants with a moderately roughened surface by anodic
      oxidation using flapless or conventional one-stage (control) surgery in
      contralateral jaw quadrants. The implants were placed into the osteotomies, and
      the international stability quotient (ISQ) was recorded using resonance frequency
      analysis. These measurements were repeated following a 3-month healing interval
      when the animals were euthanized, and implants and surrounding tissues were
      retrieved and processed for histologic analysis. RESULTS: The implants were
      stable upon insertion and demonstrated increased stability at 3 months without
      significant differences between surgical protocols. The histologic evaluation
      showed high bone-implant contact (flapless surgery: 54.7% +/- 8.4%; control:
      52.2% +/- 13.0%; P >0.05) without evidence of gingival tissue or foreign body
      inclusions. There were no significant differences in marginal bone levels between
      the surgical protocols. Post-insertion and at 3 months, ISQ values depended on
      the amount of torque delivered. Immediately post-insertion, for every 1-unit
      increase in torque value, the ISQ increased by 0.3 (95% confidence interval: 0.1
      to 0.4; P = 0.0043). Three months postoperatively, for every one-unit increase in
      torque the ISQ value decreased 0.2 (95% confidence interval: -0.4 to -0.1; P =
      0.0012). The effect of torque on ISQ values was independent of treatment effects
      and remained significant after adjustment for treatment. CONCLUSIONS: The results
      suggest that implants placed without flap reflection remain stable and exhibit
      clinically relevant osseointegration similar to when implants are placed with
      flapped procedures. Greater torque at implant placement resulted in less implant
      stability at 3 months.

PMID- 17032117
TI  - Selective cyclooxygenase-2 inhibitor may impair bone healing around titanium
      implants in rats.
AB  - BACKGROUND: The aim of this study was to investigate the effect of a selective
      cyclooxygenase-2 inhibitor, meloxicam, on bone healing around titanium implants
      in rats. METHODS: Thirty-one adult male Wistar rats were included in this study,
      and one screw-shaped titanium implant was inserted in the tibiae of each rat. The
      animals were randomly assigned to one of the following groups for daily
      subcutaneous injections: control (N = 14): saline solution; and test (N = 17): 3
      mg/kg of meloxicam, each administered daily for 60 days. After the treatment,
      animals were sacrificed, and undecalcified sections were obtained. Bone-to
      implant contact (BIC) and bone area (BA) within the limits of implant threads and
      bone density (BD) in a 500 mum-wide zone lateral to the implants were obtained
      and arranged for cortical (zone A) and cancellous (zone B) bone regions. RESULTS:
      Intergroup comparisons demonstrated that meloxicam significantly reduced bone
      healing around implants. For zone A, significant differences were observed
      regarding BIC (47.01 +/- 10.48 A; 35.93 +/- 12.25 B), BA (86.42 +/- 3.66 A; 61.58
      +/- 12.09 B), and BD (96.86 +/- 0.96 A; 91.06 +/- 3.05 B) for control and test
      groups, respectively (P <0.05). For zone B, data analysis also showed significant
      differences among groups for BIC (30.76 +/- 13.80 A; 16.86 +/- 11.48 B), BA
      (34.83 +/- 8.18 A; 25.66 +/- 9.16 B), and BD (15.76 +/- 7.05 A; 7.73 +/- 4.61 B)
      for control and test groups, respectively (P <0.05). CONCLUSION: Meloxicam may
      negatively influence bone healing in the cortical and cancellous bone around
      titanium implants inserted in rats after continuous administration.

PMID- 17032116
TI  - A Hepatocyte Growth Factor (HGF)/receptor autocrine loop regulates constitutive
      self-renewal of human periodontal ligament cells but reduces sensitivity to
      exogenous HGF.
AB  - BACKGROUND: In addition to its prominent role in liver regeneration, hepatocyte
      growth factor (HGF) is now generally thought to be produced by mesenchymal cells
      to promote the regeneration of epithelial tissue by a paracrine mechanism.
      However, it is not known how or if HGF could be involved in the regeneration of
      periodontal tissues. The purpose of this study was to characterize the ability of
      normal human periodontal ligament (PDL) cells to produce or respond to HGF.
      METHODS: PDL cells derived from healthy young volunteers were used from passages
      four through 10. HGF receptors were detected both by immunocytochemical staining
      and Western-blotting analysis. Both DNA synthesis (by bromo-deoxyuridine [BrdU]
      incorporation) and secreted HGF were quantified by enzyme-linked immunosorbent
      assays. Mitogen-activated protein kinase (MAPK) phosphorylation was also analyzed
      by Western blot. RESULTS: Despite the immunocytochemical demonstration of HGF
      receptor protein in the cytoplasm and on the plasma membrane of PDL cells,
      exogenous recombinant human HGF did not exert the mitogenic effects expected. As
      reported for other mesenchymal cells, PDL cells were found to secrete HGF.
      Treatments with neutralizing anti-HGF antibody significantly suppressed
      constitutive PDL cell proliferation and sustained the receptor protein at higher
      levels than in non-treated cells. Under these conditions, exogenous HGF rapidly
      phosphorylated extracellular signal-regulated kinase (ERK), an action linked to
      the cell proliferation and downregulation of cell-surface receptors. CONCLUSIONS:
      Unlike other known mesenchymal or epithelial cells, these findings suggest that
      normal PDL cells from young donors possess a constitutive HGF/receptor autocrine
      loop that normally regulates their replacement self-proliferation but reduces
      sensitivity to exogenously applied HGF by acute receptor downregulation.

PMID- 17032118
TI  - Histologic evaluation of early human bone response to different implant surfaces.
AB  - BACKGROUND: Studies have demonstrated that roughened dental implant surfaces show
      firmer bone fixation and an increased percentage of bone-to-implant contact
      (BIC%) compared to commercially pure titanium-surface (machined) implants.
      Therefore, the purpose of this study was to evaluate the influence of implant
      surface topography on human bone tissue after 2 months of unloaded healing.
      METHODS: Fourteen subjects with a mean age of 46.87 +/- 9.45 years received two
      microimplants each (2.5 mm in diameter and 6 mm in length), one test (sandblasted
      acid-etched surface) and one control (machined surface), either in the mandible
      or in the maxilla. After a healing period of 2 months, the microimplants and
      surrounding tissues were removed with a trephine bur and prepared for histologic
      analysis. RESULTS: All microimplants, except for one of the controls, were
      clinically stable after the healing period. Histometric evaluation indicated that
      the mean BIC% was 23.08% +/- 11.95% and 42.83% +/- 9.80% for machined and rough
      microimplant surfaces, respectively (P = 0.0005). The bone area within the
      threads was also higher for sandblasted-surface implants (P = 0.0005). The mean
      percentage of bone density did not differ between the two groups (P = 0.578).
      CONCLUSION: Data from the present histological study suggest that the sandblasted
      acid-etched implant provides a better human bone tissue response than machined
      implants under unloaded conditions after a healing period of 2 months.

PMID- 17032119
TI  - The association between cumulative periodontal disease and stroke history in
      older adults.
AB  - BACKGROUND: Since the late 1980s, several studies have been conducted to
      investigate the relationship between periodontal disease and ischemic stroke. The
      purpose of this study is to investigate the relationship of periodontal disease
      to the self-reported history of stroke in the elderly (60 years of age and older)
      by examining the data of the Third National Health and Nutrition Examination
      Survey (NHANES III). METHODS: Data from NHANES III, a large population-based
      cross-sectional survey of the United States, were used for this study. Because
      1,563 of the 5,123 subjects in the study were edentulous, and periodontal disease
      is a major cause of tooth loss, it was necessary to account for edentulousness in
      the statistical analysis to avoid bias. Hence, a new index called the periodontal
      health status (PHS) index was developed to address this problem. Two measures of
      PHS were developed: PHS I, based on the median percentage of sites with >/=2 mm
      clinical attachment loss (CAL), and PHS II, based on the median percentage of
      sites with >/=3 mm CAL. Multiple logistic regression analysis was used to test
      for the association of PHS with stroke history. Two types of a multiple logistic
      regression model were fit: 1) logistic regression modeling with adjustment for
      age and tobacco use only; and 2) logistic regression modeling with adjustment of
      all statistically significant confounders. RESULTS: Based on multiple logistic
      regression analysis of PHS with adjustment for age and tobacco use only,
      completely edentulous elderly adults (PHS Class 5) and partially edentulous
      (teeth in one arch) elderly adults with appreciable clinical attachment loss (PHS
      Class 4) were significantly more likely to have a history of stroke compared to
      dentate adults (teeth in both arches) without appreciable clinical attachment
      loss (PHS Class 1). When multiple logistic regression models were fit with
      adjustment of all significant confounders, no statistically significant
      association was found between PHS and stroke. CONCLUSIONS: Based on the results
      of this study, there is evidence of an association between cumulative periodontal
      disease, based on PHS, and a history of stroke. However, it is unclear whether
      cumulative periodontal disease is an independent risk factor for stroke or a risk
      marker for the disease.

PMID- 17032120
TI  - Prevalence of different types of accessory canals in the furcation area of third
      molars.
AB  - BACKGROUND: Although there are several studies that show the prevalence and
      diameter of accessory root canals in the furcation area, there is a scarceness of
      studies that observe the trajectory and different types of cavo-interradicular
      canals. The aim of this study was to verify the prevalence of the different
      morphologic types of accessory canals in the furcation region in an attempt to
      show their trajectories. METHODS: Forty submerged mandibular third molars were
      used, which were extracted and decalcified so that the microtomy procedure in the
      mesio-distal axial plane could be performed, obtaining semiserial sections with
      thicknesses of 5 microm. The sections were stained with hematoxylin and eosin and
      observed under optical microscopy. RESULTS: All of the morphologic types were
      found, whereas the proper accessory canals, type-A canals, were present in 10% of
      the specimens. The most prevalent canals were the sealed ones (type D), with a
      prevalence of 87.5%, followed by the blind ones (type B), with a prevalence of
      75%. The loop accessory canals (type C), observed in only 5% of the teeth, were
      the least prevalent ones. CONCLUSIONS: Different morphologic types of accessory
      canals were found in the furcation area of submerged mandibular molars. The
      histologic method was effective to show the canal trajectories.

PMID- 17032121
TI  - Local gingival blood flow at healthy and inflamed sites measured by laser Doppler
      flowmetry.
AB  - BACKGROUND: This investigation aimed to: 1) develop a method to obtain
      reproducible laser Doppler flow readings (LDFRs) at the gingiva of the maxillary
      front teeth; 2) evaluate regional gingival blood flow (GBF) in healthy gingiva by
      laser Doppler flowmetry; 3) compare hand-held LDFR (H-LDFR) with splint LDFR (S
      LDFR); and 4) monitor changes in GBF in experimental gingivitis (EG) and chronic
      gingivitis (CG). METHODS: The LDFR, gingival index (GI), and plaque index (PI)
      were measured at 13 gingival sites (teeth #6 to #11) in 10 healthy volunteers
      (five males and five females), 23 to 34 years of age, over a period of 12.5 +/-
      3.27 days employing a partial-mouth EG model and in 11 patients (three males and
      eight females), 20 to 63 years or age, with CG. LDFRs were obtained by S-LDFR or
      H-LDFR. RESULTS: H-LDFRs were significantly higher than S-LDFRs (P <0.05). All EG
      subjects developed gingivitis (PI: 2.77 +/- 0.23; GI: 1.5 +/- 0.53). EG-LDFRs at
      diseased sites increased slightly but not significantly over the study period.
      All CG-patients had high plaque and inflammation scores (PI: 2.8 +/- 0.2; GI:
      1.63 +/- 0.78). CG-LDFRs at sites with GI >1 were significantly higher than LDFRs
      at healthy sites (P <0.05). CG-LDFRs were significantly higher than EG-LDFRs at
      sites with a comparable GI (P <0.05). CONCLUSIONS: LDFRs are positively
      correlated with the degree of gingival inflammation. GBF demonstrated significant
      differences in EG and CG. Modifications of the probe are needed to enhance its
      clinical applicability in clinical research of periodontal diseases.

PMID- 17032122
TI  - High expression levels of receptor activator of nuclear factor-kappa B ligand
      associated with human chronic periodontitis are mainly secreted by CD4+ T
      lymphocytes.
AB  - BACKGROUND: Chronic periodontitis is an infectious disease characterized by
      alveolar bone destruction and teeth loss. Receptor activator of nuclear factor
      kappa B ligand (RANKL) is an osteoclastogenic cytokine, a central regulatory
      factor in the osteoclast's lifespan, and a participant in physiological and
      pathological bone resorption. Gingival T cells synthesize RANKL, contributing to
      molecular local imbalance that entails the alveolar bone resorption seen in
      periodontitis. Our study was aimed at associating the levels of RANKL with the
      CD4(+) T-cell activity present in gingival tissues of chronic periodontitis
      patients. METHODS: Gingival biopsies were obtained from 33 chronic periodontitis
      patients and 20 healthy controls. Specimens were either formalin fixed and
      paraffin embedded for real-time reverse transcription-polymerase chain reaction
      (RT-PCR) and histologic analysis or tissue digestion processed for cell culture
      and flow-cytometry analysis. RANKL mRNA and protein levels were determined by
      quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) in gingival
      cell culture supernatants. Gingival leukocytes were quantified by flow cytometry.
      RANKL and CD4 immunoreactivity were analyzed by flow cytometry and confocal
      microscopy. RESULTS: RANKL mRNA levels were higher in patients with periodontitis
      than in healthy subjects, and spontaneous and lipopolysaccharide (LPS)- and
      phytohemagglutinin (PHA)-stimulated RANKL synthesis were higher also in patients
      than controls. CD4(+) T lymphocytes were the predominant infiltrate cell subset
      present in gingival tissues of periodontitis patients. Furthermore, an
      association between RANKL and CD4(+) T cells was determined by double-staining
      flow cytometry and confocal microscopy. CONCLUSION: Taken together, these data
      demonstrate that gingival CD4(+) T cells are the main cells responsible for
      higher levels of RANKL observed in human chronic periodontitis patients.

PMID- 17032123
TI  - Bioabsorbable membrane and bioactive glass in the treatment of intrabony defects
      in patients with generalized aggressive periodontitis: results of a 5-year
      clinical and radiological study.
AB  - BACKGROUND: The aim of this clinical and radiological prospective 5-year study
      was to compare the long-term effectiveness of a bioabsorbable membrane and a
      bioactive glass in the treatment of intrabony defects in patients with
      generalized aggressive periodontitis. METHODS: Sixteen patients (11 women and
      five men) with generalized aggressive periodontitis were enrolled in the study.
      The investigations were confined to 1- to 3-walled intrabony defects with a depth
      >/=4 mm and with preoperative probing depths (PDs) >/=7 mm. Teeth with furcation
      involvement were excluded. Twenty-two of the defects were treated with the
      membrane (RXT group) and 20 with the bioactive glass (PG group). Allocation to
      the two groups was randomized. The clinical parameters plaque index (PI),
      gingival index (GI), PD, bleeding on probing (BOP), gingival recession (GR),
      clinical attachment level (CAL), and tooth mobility were recorded before surgery
      and at 6 months and every year for 5 years after surgery. Intraoral radiographs
      were taken using a standardized paralleling technique at baseline and every year
      for 5 years. Statistical analysis was based on Kolmogorov-Smirnov and Wilcoxon
      signed-rank tests, analysis of covariance, and Spearman's bivariate correlation
      analysis. RESULTS: After 5 years, a reduction in PD of 3.6 +/- 0.8 mm (P = 0.016)
      and a gain in CAL of 3.0 +/- 2.0 mm (P = 0.01) were registered in the RXT group.
      There was a slight increase in GR by 0.6 +/- 1.4 mm (P = 0.334). In the PG group,
      a reduction in PD of 3.5 +/- 1.4 mm (P = 0.01) and a gain in CAL of 3.3 +/- 2.1
      mm (P = 0.01) were recorded, whereas GR increased by 0.2 +/- 1.7 mm (P = 0.525).
      The 1-, 2-, 3-, and 4-year results did not differ significantly from the 5-year
      results. Radiographically, the defects (the point on the proximal surface of the
      defective tooth at which the projected alveolar crest intersected the root
      surface [xCA] to the most coronally located point at the proximal surface of the
      tooth on the defect side up to which the periodontal ligament space still
      displayed a uniform width [xBD]) were found to be filled by 47.5% +/- 38.3% (P =
      0.001) in the RXT group and by 65.0% +/- 50.5% (P = 0.001) in the PG group.
      Crestal resorption (the most apical point of the enamel at the proximal surface
      of the tooth on the defect side [xCEJ] to the xCA) was 19.0% +/- 30.2% (P =
      0.374) in the RXT group and 12.3% +/- 38.6% (P = 0.647) in the PG group. The xCEJ
      to the xBD was significantly more in the PG group (28.4 +/- 24.6 versus 7.3 +/-
      21.8, P = 0.048). A good standard of oral hygiene and inflammation-free
      periodontal tissue in the postoperative phase improved the treatment outcome. No
      dependence of attachment gain was found on the tooth type, number of walls
      involved in the defects (r = 0.075; P = 0.319), or intraoperative depth (r =
      0.114; P = 0.307). CONCLUSIONS: Highly significant improvements in the parameters
      PD and CAL were recorded after 5 years with both regenerative materials.
      Radiographically, the defects (the xCED to the xBD) were found to be filled
      significantly more in the bioactive glass group. A good standard of oral hygiene
      and inflammation-free periodontal tissue in the postoperative phase improved the
      treatment outcome.

PMID- 17032124
TI  - The papilla amplification flap for the treatment of a localized periodontal
      defect associated with a palatal groove.
AB  - BACKGROUND: Teeth with a palatal groove often present with severe localized
      periodontal attachment loss including pocket formation and alveolar bone loss.
      The aim of the present case report was to describe the regenerative surgical
      treatment of periodontal and bone lesions associated with the subgingival
      extension of a palatal groove affecting a maxillary lateral incisor. METHODS: The
      left maxillary lateral incisor of a systemically healthy young subject presented
      with a palatal probing depth of 10 mm with no gingival recession at the buccal
      and palatal surfaces; the neighboring interdental papillae were intact. The
      radiograph showed a radiolucency area distal to the affected tooth. Treatment
      procedures consisted of: 1) the papilla amplification flap with the use of enamel
      matrix proteins as the regenerative periodontal material; 2) the
      elimination/flattening of the radicular portion of the palatal groove; and 3) the
      sealing of the coronal portion of the groove with composite flow. RESULTS: The
      clinical examination at 1 year revealed a clinical attachment gain (8 mm) with a
      shallow residual probing depth (2 mm) and no increase in gingival recession. The
      radiographic examination showed the complete disappearance of the radiolucency
      area suggesting bone fill. CONCLUSIONS: The present study indicated that
      localized periodontal defects associated with a palatal groove can be
      successfully treated by means of the papilla amplification flap with the use of
      enamel matrix protein as the regenerative material. The long-term stability of
      such successful results needs to be determined.

PMID- 17032125
TI  - Solitary superficial microcystic lymphatic malformation (lymphangioma
      circumscriptum) of the gingiva.
AB  - BACKGROUND: Lymphatic malformations are uncommon, hamartomatous, developmental
      aberrations of the lymphatic system. The case presented in this report is a rare
      solitary gingival involvement of a microcystic-type lymphatic malformation.
      METHODS: The lesion presented clinically as a small vesicular swelling of a
      buccal interdental papilla in a 16-year-old girl. Involved tissues were excised
      and submitted for routine histologic examination. The expression of the
      endothelial marker CD34 was investigated using immunohistochemical staining.
      RESULTS: A physical examination failed to reveal similar or other abnormalities
      elsewhere in the body of the patient, including the oral cavity. Histopathologic
      analysis of the specimen demonstrated the presence of subepithelial, thin-walled,
      distended vascular cavities forming confluent vesicles containing lymph. The
      dilated lymphatic formations were lined by flattened CD34-negative endothelial
      cells. These features were consistent with a microcystic gingival lymphatic
      malformation. To the best of our knowledge, only two additional reports of this
      malformation have been published to date, but both presented with bilateral
      gingival involvement. CONCLUSION: Even though lymphatic malformations are
      encountered very infrequently on gingiva, they should be considered in the
      differential diagnosis of related conditions with a vesicular clinical
      appearance.

PMID- 17032126
TI  - Multiplexed testing in the autoimmunity laboratory.
AB  - A variety of technologies for autoantibody profiling have been developed. The
      main techniques are line-blot immunoassays, bar-coded nanoparticle immunoassays,
      and bead-based assays with flow cytometry detection and antigen microarrays. Some
      of these technologies are only able to measure a limited number of
      autoantibodies, while others can detect elevated numbers. Assays for antinuclear
      antibody specificities using line-blot immunoassays and bead-based assays with
      flow cytometry detection are already commercialised. Antigen microarrays for
      autoantibody measurement are only in the development phase, although in the not
      too distant future these assays will probably appear on the market. Multiplexed
      testing in the autoimmunity laboratory appears to have a promising future, since
      this technique permits a reduction in analytical time, with a shorter turnaround
      time.

PMID- 17032127
TI  - Uncertainty calculation for calibrators and controls of laboratory diagnostic
      assays.
AB  - The uncertainty of the results from calibrators and controls is an important
      component of the overall uncertainty of the results of medical samples. The
      purpose of this note is to review procedures of standardization and to describe
      the respective calculation of the uncertainty components for calibrators and
      controls of commercial routine diagnostic assays. The authors hope that the
      laying out of the procedures for uncertainty calculation of routine calibrators
      and controls contributes (i) to the transparency on how this component of
      uncertainty is derived and (ii) to a better understanding and use of the
      uncertainty concept in the routine laboratory.

PMID- 17032128
TI  - Westgard multirule for calculated laboratory tests.
AB  - BACKGROUND: In clinical laboratories, many test results such as low-density
      lipoprotein (LDL)-cholesterol can be calculated using the results of specifically
      measured tests. However, quality control programs deal only with measured tests
      and there is no adequate quality assessment procedure for calculated tests. I
      aimed to apply the Westgard multirule to calculated tests as a part of routine
      quality procedures. METHODS: I prepared a Levey-Jennings chart for calculated
      tests and all their measured components (Equation chart) and then applied the
      Westgard multirule to these tests. RESULTS: Applying the Westgard multirule to
      calculated LDL-cholesterol (and other calculated tests) was simple, and increased
      the reliability of the results of the calculated tests. CONCLUSIONS: Checking the
      reliability of only measured tests by quality control procedures before reporting
      patient results may be inadequate. Applying the Westgard multirule to calculated
      tests as part of total quality management will increase the reliability of test
      results.

PMID- 17032129
TI  - Frequency of a single nucleotide (A2317G) and 56-bp variable number of tandem
      repeat polymorphisms within the deoxyribonuclease I gene in five ethnic
      populations.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) at deoxyribonuclease I
      (DNase I), designated as DNASE1 (NCBI SNP number; 1053874), in exon 8 (A2317G) is
      considered to be one of the susceptibility genes for gastric and colorectal
      carcinoma and myocardial infarction. Recently, the presence of a variable number
      of tandem repeat (VNTR) polymorphisms, designated as HumDN1, in intron 4 was
      found. METHODS: Simultaneous genotyping of the DNASE1 and HumDN1 polymorphisms
      within the DNase I gene was performed in Ovambo, Turkish, Mongolian, Korean, and
      Japanese populations. RESULTS: The allele frequencies of the DNASE1 and HumDN1
      loci differed among five populations. There was general uniformity for the two
      polymorphisms in the three Asian populations, but significant differences in
      genotype distribution between the Ovambo and Turkish populations. The DNASE1 *1
      and HumDN1 *3 alleles were found to be the most predominant among the Ovambos.
      Turks had the highest allele frequency for DNASE1 *2, HumDN1 *4, and HumDN1 *5. A
      linkage disequilibrium between the single-nucleotide (A2317G) and 56-bp VNTR
      polymorphisms was revealed in all populations except the Ovambos. CONCLUSIONS:
      This study is the first to demonstrate the simultaneous genotyping of DNASE1 and
      HumDN1 polymorphisms and reveal the existence of a certain genetic heterogeneity
      in the worldwide distribution of these two polymorphisms. The combination of the
      two polymorphisms within a DNase I gene may be potentially useful for clinical
      purposes and in population genetic studies.

PMID- 17032130
TI  - The influence of genetic polymorphisms of cytochrome P450 3A5 and ABCB1 on
      starting dose- and weight-standardized tacrolimus trough concentrations after
      kidney transplantation in relation to renal function.
AB  - BACKGROUND: Cytochrome P450 3A5 (CYP3A5) and ABCB1 polymorphisms have been shown
      to influence tacrolimus (Tc) blood concentrations in the stable phase after organ
      transplantation. We hypothesized that Tc pharmacokinetics may be affected by
      genetic mutations subsequent to starting doses. METHODS: We retrospectively
      analyzed data from a cohort of 59 kidney transplant recipients, in whom CYP3A5
      (intron 3) and ABCB1 (exons 12, 21 and 26) genotypes were correlated to dose- and
      weight-standardized Tc trough concentrations obtained after initial Tc doses.
      Renal function, expressed as glomerular filtration rate (GFR) (MDRD equation), on
      days 7 and 14 after transplantation was evaluated and its relationship with Tc
      concentrations was analyzed. RESULTS: Dose- and weight-standardized Tc trough
      concentrations were lower in patients carrying the CYP3A5 *1 allele (p<0.01).
      There was no statistically significant association with ABCB1 polymorphisms. In a
      multivariate analysis, both the presence of at least one CYP3A5 *1 allele
      (p=0.006) and age at the time of transplantation (p=0.010) were significant
      independent variables affecting Tc trough blood concentrations standardized to
      the first dosages (model r2=0.23). GFR was not affected by Tc concentrations.
      CONCLUSIONS: Prospective trials are needed to prove that a genetic approach to Tc
      pharmacokinetics and its related side effects during the early period after
      grafting may improve patient outcome.

PMID- 17032131
TI  - Apolipoprotein B gene 3'VNTR polymorphism: association with plasma lipids and
      coronary heart disease in Han Chinese.
AB  - BACKGROUND: Studies that considered polymorphisms within the apolipoprotein B
      (APOB) gene as risk factors for coronary heart disease (CHD) have reported
      conflicting results. METHODS: The phenotypic effects of the 3'VNTR polymorphism
      of the APOB gene on the susceptibility to CHD were investigated in 120 unrelated
      healthy individuals and 137 CHD patients. The internal structure of APOB gene
      3'VNTR alleles was also analyzed by the methods of SspI restriction mapping and
      DNA sequencing of the allele fragments. RESULTS: In total, 14 segregating alleles
      and 32 genotypes of APOB gene 3'VNTR were characterized in the pooled total of
      257 subjects. The frequency of 3'VNTR-B alleles [hypervariable element (HVE) > or
      =38)] in the CHD cases was higher than that of the controls (10.95% vs. 5.00%,
      p<0.05). 3'VNTR-B allele was dependently related to total cholesterol levels
      (p<0.05). Compared with SS homozygotes, 3'VNTR-B allele carriers were associated
      with an increased risk of CHD (OR=2.137, 95% CI=1.055-4.328, p=0.0349). No
      significant differences in the internal structure and sequences of APOB gene
      3'VNTR alleles were found between cases and controls. CONCLUSIONS: APOB gene
      3'VNTR polymorphism exerts an impact on lipid metabolism and may contribute to
      the susceptibility to the development of CHD in Han Chinese.

PMID- 17032132
TI  - Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of
      coronary artery disease in a middle-aged Serbian population.
AB  - BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated
      serum enzyme that protects lipoproteins from oxidative modifications.
      Polymorphisms in the gene, including PON1Q192R, have been studied. However,
      inconsistencies regarding the above-mentioned polymorphism obscure its
      association with vascular disease. METHODS: Using a two-substrate
      (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R
      phenotypes in 261 middle-aged subjects: 156 patients with angiographically
      assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control
      group. The PON1(192) phenotype was predicted from examination of the two
      dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the
      antimode of the histogram of the ratio of diazoxonase/paraoxonase activity.
      RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50%
      (coronary artery disease-positive, CAD+ group) vs. control population were as
      follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082);
      chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase)
      activities in the CAD+ patients when compared to the control population.
      According to logistic regression analysis, POase activity was a better predictor
      of coronary disease onset compared with DZOase activity measurements and
      PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a
      particular phenotypic group) is more important than phenotype alone in predicting
      susceptibility to coronary artery disease.

PMID- 17032133
TI  - A modified method of prothrombin time/International Normalised Ratio
      determination in capillary blood and monitoring oral anticoagulant therapy.
AB  - BACKGROUND: Oral anticoagulant therapy is monitored by a prothrombin time (PT)
      assay. The PT is standardised by the International Normalised Ratio (INR). The
      purpose of this study was to work out a modified method of PT/INR measurement in
      capillary blood for monitoring anticoagulation treatment. METHODS: Healthy
      donors, subjects with high or low haematocrit values, and oral anticoagulant
      treated patients were included in the study. Plasma and capillary blood PT/INRs
      were determined by the standard Quick clotting assay, by the modified approach
      and with the CoaguChek S analyser. RESULTS: The performance characteristics of
      the developed method were accuracy, due to taking into account whole capillary
      blood haematocrit values, and precision, due to a decrease in the viscosity of
      the analysed samples. Implementation of the modified method showed that it is
      possible to use PT values of normal plasma for capillary blood INR calculation.
      The developed method allowed the determination of PT in capillary blood within
      the haematocrit value range from 0.15 up to 0.7. For capillary blood, the results
      of the modified method closely correlated with PT/INR values determined by the
      reference Quick method in venous plasma (r=0.99) and with the CoaguChek S
      analyser (r=0.97). CONCLUSIONS: The modified method of capillary blood PT/INR
      determination could be recommended for oral anticoagulant therapy monitoring.

PMID- 17032134
TI  - Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.
AB  - BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally
      active in atherosclerosis (AS) lesions. Aspirin was found to be a potent
      inhibitor of the UPS in some tumour studies; however, its effect on AS remains to
      be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal
      diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without
      (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of
      plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin
      conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65
      were investigated by Western blotting or immunochemistry. RESULTS: Concentrations
      of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI.
      Histological analysis showed that atheroma was increased in H. Ub and
      IkappaBalpha were mainly localised in subendothelium and media vascular smooth
      muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha
      were increased, whereas p65 was lower in HI vs. H. The activity of the 20S
      proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome
      was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the
      pathogenesis of atheroma formation, the degradation of IkappaBalpha and
      pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic
      effects on AS may be via inhibition of the UPS.

PMID- 17032135
TI  - Lipid peroxidation and antioxidative status in beta-thalassemia major patients
      with or without hepatitis C virus infection.
AB  - BACKGROUND: Information pertaining to the lipid peroxidation and antioxidative
      status of patients with beta-thalassemic major, with or without hepatitis C virus
      infection, has been scanty. METHODS: We report here the results of our efforts in
      the evaluation of lipid peroxidative status, antioxidants, and vitamin A, E and C
      levels in the sera of a group of patients (n=42) with transfusion-dependent beta
      thalassemic major with or without HCV infection. RESULTS: Firstly, plasma
      thiobarbituric acid reactive substance, a lipid peroxidation product, in these
      patients was found to be increased significantly when compared to the disease
      free controls (p<0.05). Conversely, levels of plasma vitamins A, E and C were all
      shown to be drastically reduced as compared to the disease-free controls
      (p<0.01). In parallel with these data, we also found that HCV infection did play
      some role in aggravating the depletion of plasma vitamin E and C levels in the
      beta-thalassemic patients. In contrast, HCV infection did not seem to alter the
      levels of reduced glutathione (GSH) as well as antioxidant enzyme activities
      including superoxide dismutase and GSH peroxidase. CONCLUSIONS: Taken together,
      our data indicate that excessive lipid peroxidation and a profound depletion of
      plasma vitamin A, E and C levels exist in patients with beta-thalassemic major.
      These data suggest that antioxidant supplementation to the patients for the
      purpose of alleviating the oxidative stress may be warranted.

PMID- 17032136
TI  - Role of serum S100B as a predictive marker of fatal outcome following isolated
      severe head injury or multitrauma in males.
AB  - BACKGROUND: Severe traumatic brain injury (TBI) is associated with a 30%-70%
      mortality rate. S100B has been proposed as a biomarker for indicating outcome
      after TBI. Nevertheless, controversy has arisen concerning the predictive value
      of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to
      determine whether S100B serum levels correlate with primary outcome following
      isolated severe TBI or multitrauma in males. METHODS: Twenty-three consecutive
      male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS)
      3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting
      of eight healthy volunteers were enrolled in this prospective study. Clinical
      outcome variables of severe TBI comprised: survival, time to intensive care unit
      (ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU
      discharge]. Venous blood samples were taken at admission in the ICU (study
      entry), 24 h later, and 7 days later. Serum S100B concentration was measured by
      an immunoluminometric assay. RESULTS: At study entry (mean time 10.9 h after
      injury), mean S100B concentrations were significantly increased in the patient
      with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and
      patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations
      when compared with survivors (0.85 microg/L). In fact, there was a significant
      correlation between higher initial S100B concentrations and fatal outcome
      (Spearman's =0.485, p=0.019). However, there was no correlation between higher
      S100B concentrations and the presence of multitrauma. The specificity of S100B in
      predicting mortality according to the cut-off of 0.79 microg/L was 73% at study
      entry. CONCLUSIONS: Increased serum S100B levels constitute a valid predictor of
      unfavourable outcome in severe TBI, regardless of the presence of associated
      multitrauma.

PMID- 17032138
TI  - Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism.
AB  - BACKGROUND: The vesicant agents sulfur and nitrogen mustards, which contain
      chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth,
      likely changing the utilization of anaerobic glycolysis for energy generation.
      METHODS: To investigate the effect of nitrogen mustard on cellular energy
      metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a
      nitrogen mustard and an analogue of sulfur mustard, were incubated with
      radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then
      determined. RESULTS: Glycogen consumption was significantly higher in cells
      treated with HN2 in a dose-dependent manner compared to untreated cells.
      Similarly, the amount of end-product lactate was increased, but CO2 was reduced
      in HN2-treated cells. CONCLUSIONS: Lymphocytes normally use aerobic glycolysis
      under aerobic conditions, but energy metabolism predominantly involved anaerobic
      glycolysis after severe intoxication with mustard agent.

PMID- 17032137
TI  - Preanalytical and analytical variation of surface-enhanced laser desorption
      ionization time-of-flight mass spectrometry of human serum.
AB  - BACKGROUND: Surface-enhanced laser desorption-ionization time-of-flight (SELDI
      TOF) mass spectrometry of human serum is a potential diagnostic tool in human
      diseases. In the present study, the preanalytical and analytical variation of
      SELDI-TOF mass spectrometry of serum was assessed in healthy individuals.
      METHODS: Serum and plasma were obtained from healthy human individuals. Protein
      peaks in human serum and plasma were determined by SELDI-TOF mass spectrometry.
      RESULTS: The protein peaks in serum in healthy individuals showed no variation
      with gender, age, fasting, or diurnal rhythm. The intensity of protein peaks
      changed significantly during clotting of serum from 30 to 60 min, followed by
      smaller changes from 60 to 120 min. The intensity of protein peaks changed after
      60-min storage of serum at room temperature, whereas no changes were observed for
      storage on ice. The number of reproducible protein peaks in serum was determined
      on WCX2, SAX2, and IMAC30 arrays as 29, 34, and 36, respectively. The average
      coefficient of variation (CV) of the mass value of protein peaks was 0.03%. The
      intra-assay CV of peak intensity on IMAC30 arrays was 16% (10%-36%, n=8) for 36
      peaks, inter-assay CV was 18% (6%-34%, n=4) for 16 peaks, and inter-individual CV
      was 38% (16%-56%, n=16) for 20 peaks. CONCLUSIONS: The pre-analytical and
      analytical conditions of SELDI-TOF mass spectrometry of serum have a significant
      impact on the protein peaks, with the number of peaks low and the assay variation
      high. Consequently, SELDI-TOF mass spectrometry of serum needs further evaluation
      before application in clinical diagnostics.

PMID- 17032139
TI  - Partitioning reference values of several Gaussian subpopulations with unequal
      prevalence--a procedure with computer program support.
AB  - BACKGROUND: To be able to interpret laboratory values, it is essential to develop
      population-based reference intervals. A crucial consideration is whether a
      reference interval should be divided into subpopulations or not, so-called
      partitioning. There are established methods for deciding whether partitioning
      should be done or not. However, these methods are only applicable when
      partitioning into two subpopulations is considered. The primary aim of this study
      was to suggest a procedure that was also valid for several subpopulations. The
      method assumes that these subpopulations are Gaussian. Furthermore, a secondary
      aim was to provide a tailor-made computer program to support calculations.
      METHODS: The fundamental idea is to partition reference intervals if the
      proportions of the distributions of the subpopulations outside the combined
      reference limit deviate from the nominal value of 0.025. This is made possible by
      finding the combined reference interval using an equation solver algorithm.
      RESULTS: It was found that an equation solver algorithm could easily identify the
      combined reference interval when combining two or more subpopulations, even if
      these subpopulations had unequal prevalences. It was also found that this could
      be done even if the ratio between samples does not reflect the ratio between
      prevalences. Using this algorithm, it was possible to study whether the
      proportion outside the combined reference limits in any of several subpopulations
      deviated from the nominal 0.025 by such a magnitude that partitioning was
      recommended. When similar figures to those found in earlier studies with other
      methods were tested, the procedure showed consistent results with these methods.
      The procedure was also found to be applicable when several subpopulations were
      considered. As a practical result of the study, a tailor-made computer program
      was developed and is now provided over the Internet. CONCLUSIONS: The suggested
      procedure could serve as an alternative or complement to existing methods. The
      procedure provides calculations of the combined reference interval, even if
      sample fractions do not reflect prevalence fractions. The important advantage
      with the suggested procedure is the generalisation to the situation when several
      Gaussian subpopulations, possibly with unequal prevalences, are considered.
      Finally, since a tailor-made computer program is provided, the procedure is
      simple to use.

PMID- 17032140
TI  - Biovariability of plasma adiponectin.
AB  - BACKGROUND: Adiponectin is a cytokine produced by adipose tissue with insulin
      sensitising and anti-atherosclerotic effects. Low plasma adiponectin levels are
      used as a marker of the metabolic syndrome and incipient type 2 diabetes.
      METHODS: We carried out a series of studies to determine the short- and long-term
      variability of plasma adiponectin levels, including diurnal and post-prandial
      changes. These investigations also included examining the effect of frozen
      storage on plasma adiponectin levels. RESULTS: A nested study in 10 overweight
      subjects with the metabolic syndrome and 10 age- and sex-matched controls showed
      intra-subject variation in adiponectin levels over a 30-day period of 12.2% and
      18.8%, respectively, equivalent to reference change values of 1.7 and 3.6
      microg/mL. In non-obese subjects, plasma adiponectin levels varied minimally over
      a 15-month period (baseline, 8.3+/-2.9 microg/mL vs. +15 months, 8.2+/-3.0
      microg/mL, p=0.95) and showed only minor diurnal and post-prandial changes (pre
      meal, 8.2+/-3.0 microg/mL vs. 3 h post-prandial, 8.3+/-3.1 microg/mL, p=0.60).
      The adiponectin assay had an intra-assay variation of 8.8%, with storage at -30
      degrees C for 33 months or three cycles of freezing and thawing having no
      discernible effect on adiponectin levels. CONCLUSIONS: These results demonstrate
      that plasma adiponectin levels have relatively low biovariability and that
      adiponectin can be sampled fasting or non-fasting to provide a reliable marker of
      insulin resistance and incipient type 2 diabetes.

PMID- 17032141
TI  - Multicentre evaluation of a new point-of-care test for the determination of NT
      proBNP in whole blood.
AB  - BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test
      intended for the quantitative determination of N-terminal pro-brain natriuretic
      peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected
      congestive heart failure, in the monitoring of patients with compensated left
      ventricular dysfunction and in the risk stratification of patients with acute
      coronary syndromes. METHODS: A multicentre evaluation was carried out to assess
      the analytical performance of the POC NT-proBNP test at seven different sites.
      RESULTS: The majority of all coefficients of variation (CVs) obtained for within
      series imprecision using native blood samples was below 10% for both 52 samples
      measured ten times and for 674 samples measured in duplicate. Using quality
      control material, the majority of CV values for day-to-day imprecision were below
      14% for the low control level and below 13% for the high control level. In method
      comparisons for four lots of the POC NT-proBNP test with the laboratory reference
      method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept
      ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the
      POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test
      investigated showed excellent agreement, with mean differences of between -5% and
      +4%. No significant interference was observed with lipaemic blood (triglyceride
      concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to
      582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L),
      biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52
      standard or cardiological drugs in therapeutic concentrations. With bisoprolol
      and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175
      ng/L) was found. Haematocrit values between 28% and 58% had no influence on the
      test result. Interference may be caused by human anti-mouse antibodies (HAMA)
      types 1 and 2. No significant influence on the results with POC NT-proBNP was
      found using volumes of 140-165 muL. High NT-proBNP concentrations above the
      measuring range of the POC NT-proBNP test did not lead to false low results due
      to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed
      good analytical performance and excellent agreement with the laboratory method.
      The POC NT-proBNP assay is therefore suitable in the POC setting.

PMID- 17032142
TI  - Innotrac Aio!: a point-of-care or a routine analyzer? Analytical performance and
      plasma/whole blood comparison.
AB  - BACKGROUND AND METHODS: The aim of the present study was to evaluate the
      analytical performance of the Innotrac Aio! analyzer in measuring the cardiac
      markers troponin I (TnI), myoglobin (Myo) and creatine kinase-MB (CK-MB), both in
      lithium heparin plasma and in whole blood. RESULTS: TnI analytical sensitivity
      was 0.012 microg/L and the concentration corresponding to CV=10% was 0.036
      microg/L. In healthy subjects, the 99th percentile TnI values were 0.023 and
      0.016 microg/L in whole blood and in plasma, respectively. One hundred samples
      were tested both in whole blood and in plasma: TnI-whole-blood=1.16-plasma+0.011,
      bias=+0.18 (95% CI from -0.22 to +0.59); Myo-whole-blood=1.04-plasma-1.93,
      bias=+1.08 (95% CI from -6.17 to +8.32); CK-MB-whole-blood=1.11-plasma-0.09,
      bias=+0.96 (95% CI from -0.53 to +2.45). The method comparison with the RxL
      Dimension analyzer for TnI and Myo gave the following results: TnI Aio!=0.30 TnI
      RxL+0.00; bias=-5.80 (95% CI from -7.81 to -3.78), Myo Aio!=1.33 Myo RxL+0.42,
      bias=+53.09 (95% CI from +38.44 to +67.74). CONCLUSIONS: The analytical
      performance of the Innotrac Aio! analyzer was satisfactory for all three cardiac
      markers evaluated and, in particular, the TnI method provided sensitive and
      accurate results. The most important finding in this study is the possibility to
      perform the tests as either routine or point-of-care analysis, thus overcoming
      the variability of results obtained employing different methods.

PMID- 17032143
TI  - Serologic associations of anti-cytoplasmic antibodies identified during anti
      nuclear antibody testing.
AB  - BACKGROUND: There are currently no guidelines concerning additional laboratory
      testing for specific autoantibodies among anti-nuclear antibody-negative sera
      with an anti-cytoplasmic staining pattern identified by indirect
      immunofluorescence assay. Moreover, few data are available that address this
      laboratory situation. METHODS: We performed specific autoantibody assays in 200
      sera with an anti-nuclear antibody titer < or =1:32 and a cytoplasmic titer
      (undefined staining pattern) of > or =1:64, identified sequentially in the course
      of routine anti-nuclear antibody testing. RESULTS: A total of 85 sera (42.5%)
      were positive in one (n=57) or more (n=28) of the specific autoantibody tests
      performed. Autoantibodies identified were antimitochondrial (15%), antimicrosomal
      (13%), anti-neutrophil cytoplasmic (10%), anti-smooth muscle (6%), anti-parietal
      cell (4%), and extractable nuclear antigen (8.5%, including histones, SSA, SSB,
      Sm, Jo-1 or Scl-70). A positive result in one or more of these assays was more
      frequent at anti-cytoplasmic titers > or =1:1024 (77.8%) than at titers of 1:64
      1:128 (7%) (chi2=25.3, p<0.001). CONCLUSIONS: The present data demonstrate that
      undefined anti-cytoplasmic staining in anti-nuclear antibody-negative sera is
      associated with, although not necessarily caused by, a high frequency and wide
      range of specific autoantibodies. Further work is needed before specific
      recommendations can be made concerning follow-up in subjects with this laboratory
      finding.

PMID- 17032144
TI  - The importance of metrological traceability on the validity of creatinine
      measurement as an index of renal function.
AB  - The glomerular filtration rate (GFR) is currently considered the best overall
      index of kidney function. The possibility that laboratories might routinely
      report an estimated GFR has become practically feasible with the development of a
      formula, the "four-variable" Modification of Diet in Renal Disease study (MDRD)
      equation that uses age, sex, race, and serum creatinine parameters. However, a
      limitation of this equation for general implementation in healthcare is related
      to the use of differently calibrated creatinine measurement procedures among
      laboratories. The only way to achieve universal implementation of the GFR
      prediction equation, with the associated clinical benefits for patients, is,
      therefore, to promote worldwide standardization of methods to determine
      creatinine, together with the introduction of a revised GFR-estimating equation
      appropriate for use with standardized creatinine methods.

PMID- 17032145
TI  - Effect of seropositive rheumatoid factor on cardiac troponin I measurement using
      the Access immunoassay analyzer.

PMID- 17032146
TI  - Associations between homocysteine, bone turnover, BMD, mortality, and fracture
      risk in elderly women.
AB  - Homocysteine has been suggested to be a risk factor for fracture, but the causal
      relationship is not clear. In 996 women from the OPRA study, high homocysteine
      level was associated with high bone marker levels and low BMD at baseline. During
      a mean 7-year follow-up, high homocysteine level was associated with mortality,
      but no clear association to fracture risk existed. INTRODUCTION: Recently, the
      association between high serum homocysteine (Hcy) levels and an increased risk of
      fracture has been described. MATERIALS AND METHODS: Hcy levels were measured at
      baseline in 996 women, all 75 years old. Vitamin B(12), folate, serum cross
      linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin,
      urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound
      (QUS), and physical performance were assessed at baseline. Fractures and
      mortality were recorded during a mean follow-up of 7.0 years. RESULTS: Bone
      marker levels were higher in women with Hcy in the highest quartile compared with
      all other women (p < 0.05). The most evident correlation between Hcy and a bone
      marker was seen with CTX (r = 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was
      up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest
      quartile compared with the other women (p < 0.05). During the follow-up, 267
      women sustained at least one low-energy fracture (including 69 hip fractures).
      When women in the highest Hcy quartile were compared with all other women, the
      hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89
      1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of
      women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for
      confounders did not substantially change these associations. Adjustment for PTH
      increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B(12)
      or folate was not associated with increased fracture risk or mortality.
      CONCLUSIONS: High Hcy levels were associated with higher bone turnover, poor
      physical performance, and lower BMD. There was no clear association to fracture
      risk. The increased mortality among women with high Hcy levels indicates that a
      high Hcy level may be a marker of frailty.

PMID- 17032147
TI  - TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.
AB  - Bone metastases develop in approximately 30% of patients with RCC, and the
      mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1
      stimulation of RCC bone metastasis cells promotes tumor growth and bone
      destruction possibly by stimulating paracrine interactions between tumor cells
      and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes
      marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the
      specific mechanisms of RCC interaction with bone have been scarcely studied
      despite the inability to prevent or effectively treat bone metastasis. Bone is a
      reservoir for various growth factors including the pleiotropic cytokine TGF
      beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced
      cancers and evidence suggests its involvement in promoting the development of
      breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1
      in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF
      beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII
      cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and
      osteolysis was determined by histological and radiographic analysis,
      respectively, of athymic nude mice after intratibial injection of parental, empty
      vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was
      determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF
      beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM
      tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells
      significantly reduced tumor establishment and osteolysis observed in vivo after
      injection into the murine tibia, although no effect on tumor establishment was
      observed after injection of RBM cells subcutaneously or into the renal
      subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had
      no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth,
      suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo.
      CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor
      growth and subsequent osteolysis in vivo, likely through the initiation of tumor
      promoting paracrine interactions between tumor cells and the bone
      microenvironment. These data suggest that inhibition of TGF-beta1 signaling may
      be useful in the treatment of RBM.

PMID- 17032148
TI  - Long-term control of bone turnover in Paget's disease with zoledronic acid and
      risedronate.
AB  - A single 5-mg infusion of zoledronic acid restores biochemical markers of bone
      turnover into the reference range in the majority of patients with Paget's
      disease and maintains biochemical remission for at least 2 years. This effect is
      largely independent of pretreatment disease activity and prior bisphosphonate
      therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that
      produces a rapid and complete control of the increased bone turnover of Paget's
      disease. Long-term control of disease activity is an important aim of treatment
      in the hope that this will reduce the risk of complications such as deformity,
      fracture, and degenerative joint disease. MATERIALS AND METHODS: This study
      compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with
      risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control
      of bone turnover. No bisphosphonate was given during the extension study. All
      patients (n = 296) who achieved a therapeutic response, defined as normalization
      or a >75% reduction in the total alkaline phosphatase (total ALP) excess above
      the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL
      maintained the mean level of total ALP at the middle of the reference range,
      whereas those treated with risedronate showed a linear increase in total ALP from
      the 6-month post-treatment time-point. Both treatments resulted in a linear
      relationship between the 6-month nadir and 24-month total ALP. The relationship
      for RIS was shifted upward, showing that for a given level of post-treatment
      biochemical activity, bone turnover increased with time. This was in contrast to
      the ZOL-treated patients where total ALP generally remained unchanged over this
      18-month extension period. A similar pattern of response was seen with the other
      bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the
      reference range over 24 months from the initiation of treatment. A reduction in
      the incidence and severity of long-term complications may require persistent
      normalization of bone turnover over many years, and this now seems a realistic
      possibility with ZOL.

PMID- 17032149
TI  - Effect of enzyme replacement therapy with imiglucerase on BMD in type 1 Gaucher
      disease.
AB  - The effect of ERT with imiglucerase on BMD in type 1 GD was studied using BMD
      data from the International Collaborative Gaucher Group Gaucher Registry. Data
      were analyzed for 160 untreated patients and 342 ERT-treated patients.
      Imiglucerase significantly improves BMD in patients with GD, with 8 years of ERT
      leading to normal BMD. INTRODUCTION: The objective was to determine the effect of
      enzyme replacement therapy (ERT; Cerezyme, imiglucerase) on BMD in type 1 Gaucher
      disease (GD). MATERIALS AND METHODS: The study population included all adults
      (men, 18-70 years; women, 18-50 years) enrolled in the International
      Collaborative Gaucher Group (ICGG) Gaucher Registry for whom lumbar spine BMD
      measurements were available. BMD data with up to 8 years of follow-up were
      analyzed for 160 patients who received no ERT and 342 patients treated with ERT
      alone. BMD was assessed by DXA of the lumbar spine. Z scores for patients with GD
      were compared with a reference population. From the model's estimate, percent of
      patients by age and sex with osteoporosis (T score < or = -2.5) were calculated.
      RESULTS: DXA Z scores for patients with GD in the no ERT (untreated) group were
      significantly below normal (y intercept = -0.80 Z score units, p < 0.001) and
      remained approximately 1 SD below the reference population over time (slope = 
      0.010 Z score units per year, p = 0.68). The DXA Z scores for patients with GD
      who received ERT at a dose of 60 U/kg/2 weeks were significantly lower than the
      reference population at baseline (y-intercept = -1.17 Z score units, p < 0.001),
      but improved significantly over time (slope = +0.132 Z score units per year, p <
      0.001). A significant dose-response relationship was noted for the ERT group,
      with the slopes for the three main dosing groups of 15, 30, and 60 U/kg/2 weeks
      of +0.064, +0.086, and +0.132 Z score units per year, respectively. The BMD of
      patients with GD treated with ERT increased to -0.12 (60 U/kg/2 weeks), -0.48 (30
      U/kg/2 weeks), and -0.66 (15 U/kg/2 weeks) SD of the mean of the reference
      population after 8 years of ERT, approaching the reference population. Estimated
      risk of osteoporosis of this GD population, if left untreated, ranged from
      approximately 10 to 30% in women and 10% to 25% in men. CONCLUSIONS: ERT with
      imiglucerase (Cerezyme) may increase BMD in patients with GD. Response to
      treatment with imiglucerase is slower for BMD than for hematologic and visceral
      aspects of GD. A normal (age- and sex-adjusted) BMD should be a therapeutic goal
      for patients with type 1 GD.

PMID- 17032150
TI  - Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on
      BMP-stimulated bone formation.
AB  - Sclerostin is an osteocyte-derived negative regulator of bone formation. It
      inhibits BMP-stimulated bone formation both in vitro and in vivo but has no
      direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that
      is required for BMP-stimulated osteoblastic differentiation. INTRODUCTION:
      Sclerostin is a member of the Dan family of glycoproteins of which many members
      have been reported to antagonize BMP activity. Sclerostin has been shown to
      inhibit BMP-stimulated bone formation, but its mechanism of action seems to be
      different from classical BMP antagonists. In this study, we investigated the
      mechanism by which sclerostin inhibits BMP-stimulated bone formation. MATERIALS
      AND METHODS: DNA electroporation of calf muscle of mice using expression plasmids
      for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced
      bone formation in vivo. Transcriptional profiling using microarrays of
      osteoblastic cells treated with BMP in the absence or presence of sclerostin was
      used to find specific growth factor signaling pathways affected by sclerostin.
      The affected pathways were further studied using growth factor-specific reporter
      constructs. RESULTS: BMP-induced ectopic bone formation in calf muscle of mice
      was prevented by co-expression of sclerostin in vivo. Transcriptional profiling
      analysis of osteoblastic cultures indicated that sclerostin specifically affects
      BMP and Wnt signaling out of many other growth signaling pathways. Sclerostin,
      however, did not inhibit stimulation of direct BMP target genes. Furthermore, we
      did not obtain any evidence for sclerostin acting as a direct BMP antagonist
      using a BMP-specific reporter construct. In contrast, sclerostin shared many
      characteristics with the Wnt antagonist dickkopf-1 in antagonizing BMP-stimulated
      bone formation and BMP- and Wnt-induced Wnt reporter construct activation.
      CONCLUSIONS: Sclerostin inhibits BMP-stimulated bone formation but does not
      affect BMP signaling. Instead, it antagonizes Wnt signaling in osteoblastic
      cells. High bone mass in sclerosteosis and van Buchem disease may, therefore,
      result from increased Wnt signaling.

PMID- 17032151
TI  - Development of oncolytic adenovirus armed with a fusion of soluble transforming
      growth factor-beta receptor II and human immunoglobulin Fc for breast cancer
      therapy.
AB  - We have developed an approach to cancer gene therapy in which the oncolytic
      effects of an adenoviral vector have been combined with selective expression of a
      soluble form of transforming growth factor (TGF)-beta receptor II fused with Fc
      (sTGFbetaRIIFc). We chose to use adenoviral dl01/07 mutant because it can
      replicate in all cancer cells regardless of their genetic defects. An oncolytic
      adenovirus expressing sTGFbetaRIIFc (Ad.sT- betaRFc) was constructed by
      homologous recombination. Infection of MDA-MB-231 and MCF-7 human breast cancer
      cells with Ad.sTbetaRFc produced sTGFbetaRIIFc, which was released into the
      media. The conditioned media containing sTGFbetaRIIFc could bind with TGF-beta 1
      and inhibited TGF-beta-dependent transcription in target cells. Infection of MDA
      MB-231, MCF-7, and 76NE human breast cancer cells with Ad.sTbetaRFc resulted in
      high levels of viral replication, comparable to that of a wild-type dl309 virus.
      Although some viral replication was observed in actively dividing normal human
      lung fibroblasts, there was no replication in nonproliferating normal cells.
      Direct injection of Ad.sTbetaRFc into MDA-MB-231 human breast xenograft tumors
      grown in nude mice resulted in a significant inhibition of tumor growth, causing
      tumor regression in more than 85% of the animals. These results indicate that it
      is possible to construct an oncolytic virus expressing sTGFbetaRIIFc in which
      both viral replication and transgene expression remain intact, and the
      recombinant adenovirus is oncolytic in a human tumor xenograft model. On the
      basis of these results we believe that it may be feasible to develop a cancer
      gene therapy approach using Ad.sTbetaRFc as an antitumor agent.

PMID- 17032152
TI  - DNA vaccines: recent developments and future possibilities.
AB  - The field of DNA vaccines continues to advance and several new strategies to
      augment the immunogenicity of DNA vaccines are under evaluation. The majority of
      these studies are in the early preclinical stage, but some DNA vaccines have
      moved into clinical trials. In this review, we describe some of the more recent
      efforts aimed at increasing the immunogenicity of DNA vaccines, including the use
      of genetic adjuvants and plasmid-based expression of viral replicons. In
      addition, we discuss the possibility of using DNA vaccines to address emerging
      infectious agents where they may provide an advantage over other vaccine
      strategies and we review some areas where DNA vaccines have been used to target
      self-antigens.

PMID- 17032153
TI  - Recent developments in the application of plasmid DNA-based vectors and small
      interfering RNA therapeutics for cancer.
AB  - Increased understanding of the molecular pathological mechanisms of cancer, the
      advent of novel molecular tools such as synthetic small interfering RNA (siRNA)
      or plasmid DNA-based vectors (pDNA), and technology for the in vivo delivery of
      such biomolecular therapeutics have provided an encouraging perspective for
      cancer therapy. Numerous pDNAs and siRNAs have been tested in preclinical cancer
      models, and these first approaches have reached clinical evaluation. The
      therapeutic effector mechanisms include interference with neoangiogenesis,
      blockage of cell division, promotion of apoptosis and sensitization to
      chemotherapy, delivery of cytotoxic genes, and activation of anticancer immune
      responses. Physical methods have been developed for highly effective regional
      delivery. A series of innovative "smart" formulations directs the current
      development toward safe and effective systemic tumor-targeted delivery of pDNA
      and siRNA.

PMID- 17032154
TI  - Regulation of gene therapy in china.

PMID- 17032155
TI  - Targeting gene therapy for prostate cancer cells by liposomes complexed with anti
      prostate-specific membrane antigen monoclonal antibody.
AB  - Prostate-specific membrane antigen (PSMA) is a membrane-bound antigen expressed
      on the surface of prostate cancer cells, and this paper describes the use of an
      antibody against PSMA for targeting gene therapy. We coupled anti-PSMA monoclonal
      antibody with poly-L-lysine and then incubated it with plasmids. These complexes
      were then transfected with cationic liposomes into cells. The transfection
      efficiency of anti-PSMA- liposome complex was higher than that of normal IgG
      liposome complex in PSMA-positive LNCaP cells. Furthermore, anti-PSMA-liposome
      complex containing a suicide gene, thymidine kinase, demonstrated a selective
      growth-inhibitory effect on LNCaP cells in vitro, but did not exert a significant
      effect on PSMA-negative cells. In an in vivo xenograft model of LNCaP cells in
      nu/nu mice, we administered the complexes via the tail vein. Judging on the basis
      of both 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining and
      luciferase assay findings, a significant enrichment of plasmid DNA was observed
      in LNCaP xenografts with anti-PSMA-liposome complex in comparison with normal IgG
      liposome complex. However, the distribution of plasmid DNA did not change
      substantially in any other organs including the liver, kidney, lung, and spleen.
      Moreover, in suicide gene therapy, anti-PSMA-liposome complex exerted a
      significant inhibitory effect on the growth of LNCaP xenograft, in contrast to
      normal IgG-liposome complex.

PMID- 17032157
TI  - A randomized controlled trial of cognitive behavior therapy for borderline
      personality disorder: rationale for trial, method, and description of sample.
AB  - This paper describes the rationale for a randomized controlled trial, comparing
      cognitive behavior therapy in addition to treatment as usual with treatment as
      usual alone, for borderline personality disorder. Previous pioneering randomized
      controlled trials of psychotherapies have suffered from methodological weaknesses
      and have not always been reported clearly to allow adequate evaluation of either
      the individual study or comparisons across studies to be undertaken. We report on
      the recruitment and randomization, design, and conduct of an ongoing randomized
      controlled trial of one hundred and six patients with borderline personality
      disorder. Primary and secondary hypotheses and their planned analyses are stated.
      The baseline characteristics of 106 patients meeting diagnostic criteria for
      borderline personality disorder are described.

PMID- 17032158
TI  - The effectiveness of cognitive behavior therapy for borderline personality
      disorder: results from the borderline personality disorder study of cognitive
      therapy (BOSCOT) trial.
AB  - The outcome of a randomized controlled trial of cognitive behavior therapy in
      addition to treatment as usual (CBT plus TAU) compared with TAU alone (TAU) in
      one hundred and six participants meeting diagnostic criteria for borderline
      personality disorder is described. We anticipated that CBT plus TAU would
      decrease the number of participants with in-patient psychiatric hospitalizations
      or accident and emergency room contact or suicidal acts over twelve months
      treatment and twelve months follow-up, compared with TAU. We also anticipated
      that CBT plus TAU would lead to improvement in a range of secondary outcomes of
      mental health and social functioning compared to TAU. Of the 106 participants
      randomized, follow-up data on 102 (96%) was obtained at two years. Those
      randomized to CBT were offered an average of 27 sessions over 12 months and
      attended on average 16 (range 0 to 35). We found that the global odds ratio of a
      participant in the CBT plus TAU group compared with the TAU alone group having
      any of the outcomes of a suicidal act, in-patient hospitalization, or accident
      and emergency contact in the 24 months following randomization was 0.86 (95%
      confidence interval [CI] 0.45 to 1.66, p = 0.66). The corresponding global odds
      ratio, excluding accident and emergency room contact, was 0.75 (95% CI 0.37 to
      1.54, p = 0.44). In terms of the number of suicidal acts, there was a significant
      reduction over the two years in favor of CBT plus TAU over TAU, with a mean
      difference of -0.91 (95% CI -1.67 to -0.15, p = 0.020). Across both treatment
      arms there was gradual and sustained improvement in both primary and secondary
      outcomes, with evidence of benefit for the addition of CBT on the positive
      symptom distress index at one year, and on state anxiety, dysfunctional beliefs
      and the quantity of suicidal acts at two year follow-up. CBT can deliver
      clinically important changes in relatively few clinical sessions in real clinical
      settings.

PMID- 17032159
TI  - The cost-effectiveness of cognitive behavior therapy for borderline personality
      disorder: results from the BOSCOT trial.
AB  - Borderline personality disorder places a significant burden on healthcare
      providers and other agencies. This study evaluated the cost-effectiveness of
      cognitive behavior therapy plus treatment as usual compared to treatment as usual
      alone for patients with borderline personality disorder. The economic analysis
      was conducted alongside a multi-center, randomized controlled trial. The costs of
      primary and secondary healthcare utilization, alongside the wider economic costs,
      were estimated from medical records and patient self-report. The primary outcome
      measure used was the quality-adjusted life year (QALY), assessed using EuroQol.
      On average, total costs per patient in the cognitive behavior therapy group were
      lower than patients receiving usual care alone (-689 pounds sterling), although
      this group also reported a lower quality of life (-0.11 QALYs). These differences
      were small and did not approach conventional levels of statistical significance.
      The use of cognitive therapy for borderline personality disorder does not appear
      to demonstrate any significant cost-effective advantage based on the results of
      this study.

PMID- 17032160
TI  - Manual assisted cognitive treatment for deliberate self-harm in borderline
      personality disorder patients.
AB  - This study examines the efficacy of a short-term individual therapy, Manual
      Assisted Cognitive Treatment (MACT), which was developed to treat parasuicidal
      (suicidal or self-harming) patients. In this trial, MACT was modified to focus on
      deliberate self-harm (DSH) in patients with borderline personality disorder
      (BPD). Thirty BPD patients who were engaged in DSH while in ongoing treatments,
      i.e., treatment-as-usual (TAU), were randomly assigned to receive MACT (N = 15)
      or not. DSH and level of suicide ideation were assessed at the baseline, at
      completion of the MACT intervention, and six months later. Results indicated that
      MACT was associated with significantly less frequent DSH upon completion of the
      intervention and with significantly decreased DSH frequency and severity at the
      six months follow-up. Moreover, MACT's contribution to reducing DSH frequency and
      severity was greater than the contribution by the amount of concurrent
      treatments. In contrast, MACT did not affect the level of suicide ideation and
      time-to-repeat of DSH. In conclusion, MACT seems to be a promising intervention
      for DSH in patients with BPD. More definitive studies are needed.

PMID- 17032161
TI  - Six-year follow-up of three treatment programs to personality disorder.
AB  - Previous studies of long-term outcome for personality disorder (PD) were either
      retrospective in design or did not include a control condition. In this paper we
      report results for three PD cohorts (N = 111) treated in two different specialist
      psychosocial programs (step-down and long-term inpatient) and in general
      psychiatric treatment as usual (TAU), which were prospectively followed up for 72
      months after intake. The three PD samples were compared on symptom severity,
      social adjustment, global functioning and other clinical indicators (self
      mutilation, parasuicide and readmission rates) at intake, 6, 12, 24, and 72
      months. Results indicated that a specialist step-down model showed significantly
      greater change than a purely inpatient model and TAU in most key dimensions of
      functioning, a difference maintained at 72-months follow-up. Improvement in the
      samples was not associated with amount of intercurrent treatment received in the
      year prior to the follow-up assessment. This study confirms that a step-down
      program retains significant improvement associated with a specialist psychosocial
      approach for PD. However, this conclusion should be qualified by design
      limitations. The samples were not randomly allocated to the three conditions and
      the naturalistic geographical allocation used in the study created a potential
      for a number of confounds. Whilst we used extensive statistical controls, the
      possibility that the differences found between the groups may be due to
      population differences cannot be discounted.

PMID- 17032162
TI  - Relative impact of young adult personality disorders on subsequent quality of
      life: findings of a community-based longitudinal study.
AB  - Little is known about long-term prognostic implications of personality disorder
      (PD) for quality of life (QOL) in the young adult population not selected for
      psychiatric treatment. The purpose of this study was to determine the association
      of PDs with QOL assessed after an 11-year interval. PDs were assessed in 1991
      1994 at mean age 22, and indicators of QOL were assessed in 2001-2004 at mean age
      33 based on a community sample of 588 young adults. Findings indicated that any
      PD, or a cluster A, B, or C PD each were independently associated with elevated
      impairment in overall QOL after adjusting for demographic variables, co-occurring
      Axis I disorder, and physical illness, and PDs in other clusters. Cluster B PD
      had a greatest adverse impact on QOL. Symptoms of antisocial, borderline, and
      schizotypal PD symptoms were independently associated with significant reductions
      in QOL; avoidant, paranoid, and dependent PD symptoms were associated with
      smaller reductions, not reaching statistical significance. Symptoms of other
      individual PDs were not associated with reduced QOL. PDs in young adults in the
      community have an enduring and adverse impact on subsequent QOL that cannot be
      attributed to physical illness or Axis I psychiatric disorder.

PMID- 17032163
TI  - Is the appendix a useful appendage? An empirical examination of depressive,
      passive-aggressive (negativistic), sadistic, and self-defeating personality
      disorders.
AB  - Decisions about whether to include depressive, passive-aggressive, sadistic, and
      self-defeating disorders in Axis II have been made difficult by a relative dearth
      of data. We report the results of a study identifying potential defining features
      of these diagnoses and assessing their distinctiveness from other Axis II
      personality disorders (PDs). A national sample of experienced psychiatrists and
      psychologists used the SWAP-200 to describe a patient with a current axis II
      disorder or an appendix or deleted PD from DSM-II-R. We examined clinicians'
      descriptions of patients to identify their most characteristic features, and then
      applied an empirical clustering procedure, Q-factor analysis, to see whether
      versions of these disorders would emerge empirically. As currently
      conceptualized, only passive-aggressive PD was distinct from other PDs. When the
      data were subjected to Q-factor analysis, the first and largest grouping was a
      dysphoric (depressive) PD. A hostile-negativistic subcategory emerged that
      resembled passive-aggressive PD, along with a revised dependent diagnosis that
      included many self-defeating/masochistic features. The results suggest that a
      depressive or dysphoric personality may represent an internalizing spectrum of
      personality pathology, and that a hostile-negativistic PD may be distinct from
      the disorders in the text of DSM-IV. Sadistic and self-defeating PD do not appear
      to represent distinct disorders, although they include personality traits (sadism
      and revictimization) associated with distinct developmental histories.

PMID- 17032164
TI  - Mx1 and IP-10: biomarkers to measure IFN-beta activity in mice following gene
      based delivery.
AB  - Recombinant interferon-beta (IFN-beta) protein is used successfully for the
      treatment of multiple sclerosis (MS). Gene therapy might be an alternative
      approach to overcome drawbacks occurring with IFN-beta protein therapy. A
      critical issue in developing a new approach is detection of biologically active
      IFN-beta in preclinical models. The goal of the present study was to determine if
      Mx1 and IP-10, which are known to be activated after IFN-beta treatment in
      humans, can be used as biomarkers in mice. In three in vivo experiments, the
      correlation between different methods of murine IFN-beta (MuIFN-beta) delivery
      and biomarker induction was studied: (1) bolus protein delivery by intravenous
      (i.v.) or intramuscular (i.m.) injection, (2) gene-based delivery of IFN- beta by
      i.m. injection of plasmid DNA, followed by electroporation, and (3) gene-based
      delivery of IFN-beta by i.m. injection of adenovirus-associated type 1 (AAV1).
      Short-term induction of Mx1 mRNA and IP-10 was observed after treatment with
      bolus MuIFN-beta protein. Long-term induction of both biomarkers was observed
      after IFN-beta plasmid DNA delivery or when AAV1 was used as the vector. The
      experiments demonstrate that gene-based delivery provides sustained levels of IFN
      beta compared with bolus protein injection and that Mx1 RNA and IP-10 can be used
      to monitor biologically active circulating plasma MuIFN-beta protein in mice.

PMID- 17032165
TI  - The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to
      inhibit natural killer cell death.
AB  - The proinflammatory cytokine, interleukin-18 (IL-18), is a natural killer (NK)
      cell activator that induces NK cell cytotoxicity and interferon-gamma (IFN-gamma)
      expression. In this report, we define a novel role for IL-18 as an NK cell
      protective agent. Specifically, IL-18 prevents NK cell death initiated by
      different and distinct stress mechanisms. IL-18 reduces NK cell self-destruction
      during NK-targeted cell killing, and in the presence of staurosporin, a potent
      apoptotic inducer, IL-18 reduces caspase-3 activity. The critical regulatory step
      in this process is downstream of the mitochondrion and involves reduced cleavage
      and activation of caspase-9 and caspase-3. The ability of IL-18 to regulate cell
      survival is not limited to a caspase death pathway in that IL-18 augments tumor
      necrosis factor (TNF) signaling, resulting in increased and prolonged mRNA
      expression of c-apoptosis inhibitor 2 (cIAP2), a prosurvival factor and caspase-3
      inhibitor, and TNF receptor-associated factor 1 (TRAF1), a prosurvival protein.
      The cumulative effects of IL-18 define a novel role for this cytokine as a
      molecular survival switch that functions to both decrease cell death through
      inhibition of the mitochondrial apoptotic pathway and enhance TNF induction of
      prosurvival factors.

PMID- 17032166
TI  - MKK3/6-p38 MAPK signaling is required for IL-1beta and TNF-alpha-induced RANKL
      expression in bone marrow stromal cells.
AB  - Coupled bone turnover is directed by the expression of receptor-activated NF
      kappaB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG).
      Proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha (TNF-alpha) induce RANKL expression in bone marrow stromal
      cells. Here, we report that IL-1beta and TNF-alpha-induced RANKL requires p38
      mitogen-activating protein kinase (MAPK) pathway activation for maximal
      expression. Real-time PCR was used to assess the p38 contribution toward IL-1beta
      and TNF-alpha-induced RANKL mRNA expression. Steady-state RANKL RNA levels were
      increased approximately 17-fold by IL-1beta treatment and subsequently reduced
      approximately 70%-90% when p38 MAPK was inhibited with SB203580. RANKL mRNA
      stability data indicated that p38 MAPK did not alter the rate of mRNA decay in IL
      1beta-induced cells. Using a RANKL-luciferase cell line receptor containing a 120
      kB segment of the 5' flanking region of the RANKL gene, reporter expression was
      stimulated 4-5-fold by IL-1beta or TNF-alpha treatment. IL-1beta-induced RANKL
      reporter expression was completely blocked with specific p38 inhibitors as well
      as dominant negative mutant constructs of MAPK kinase-3 and -6. In addition,
      blocking p38 signaling in bone marrow stromal cells partially inhibited IL-1beta
      and TNF-alpha-induced osteoclastogenesis in vitro. Results from these studies
      indicate that p38 MAPK is a major signaling pathway involved in IL-1beta and TNF
      alpha-induced RANKL expression in bone marrow stromal cells.

PMID- 17032167
TI  - Modulation of immune responses induced by DNA vaccine expressing glycoprotein B
      of Pseudorabies Virus via coadministration of IFN-gamma-associated cytokines.
AB  - The immunomodulatory efficacy of interferon-gamma (IFN-gamma)-associated
      cytokines coadministered with a plasmid DNA vaccine has been investigated, with
      variable results. Therefore, to test the immunomodulatory effect of IFN-gamma
      associated cytokines as vaccine adjuvant, the present study evaluated the immune
      responses induced by pseudorabies virus (PrV) gB-encoded plasmid DNA vaccine
      coadministered with IFN-gamma-associated cytokines and chemokines. These
      cytokines and chemokines included interleukin-12 (IL-12) and IL-18, as potent
      inducers of IFN-gamma, and IFN-gamma-inducible protein (IP-10), the production of
      which is IFN-gamma dependent. A coinjection of either IL-12 or IL-18 strongly
      suppressed the humoral antibody responses but increased the production of the Th1
      type cytokines IFN-gamma and IL-2 from immune T cells. Such antibody suppression
      was closely related to the increased susceptibility against a virulent viral
      challenge. On the other hand, IP-10 exhibited enhanced immune responses in both
      antibody responses and IFN-gamma production of immune T cells and facilitated the
      prolonged survival of infected mice. In contrast, there was no significant change
      in the immune responses of the mice that received codelivery of IFN-gamma.
      Therefore, IFN-gamma-associated cytokines, as Th1-type inducers, can generate
      unexpected and unwanted effects, and their application as a vaccine adjuvant
      should be carefully evaluated depending on the target antigens.

PMID- 17032168
TI  - A role for Stat1 in the regulation of lipopolysaccharide-induced interleukin
      1beta expression.
AB  - Because the induction of interleukin-1beta (IL-1beta) is critical to
      antibacterial host defenses and its excessive generation is a prominent component
      of sepsis, regulation of this proinflammatory cytokine is a critical factor in
      the immune response to lipopolysaccharide (LPS). We previously showed that LPS
      induced IL-1beta expression was regulated by a Stat1-dependent, nitric oxide (NO)
      mediated mechanism. Subsequent in vivo studies showed that whereas Stat1 had a
      role in the downregulation of IL-1beta expression, it had a more significant
      effect on its initial induction. Although both interferon-beta (IFN-beta) and IFN
      gamma activate Stat1, the early appearance of IFN-beta in the circulation after
      LPS administration suggested its pivotal role in Stat1-mediated IL-1beta
      expression in vivo. Further in vitro analysis of peritoneal macrophages from IFN
      beta (/), Stat1(/), and caspase-1(/) mice and their wild-type controls following
      LPS stimulation demonstrated that IL-1beta mRNA was expressed in these mice but
      not in macrophages from MyD88(/) mice. Despite the presence of IL-1beta mRNA, IL
      1beta protein was markedly reduced in the absence of Stat1 activation in
      macrophages derived from IFN-beta (/) and Stat1(/) mice or in the absence of
      caspase-1 activity, which itself was dependent on Stat1 activation. These studies
      support the hypothesis that the expression of IL-1beta requires both the MyD88
      dependent induction of IL-1beta mRNA and pro-IL-1beta as well as the MyD88
      independent, Stat1-mediated processing of that gene product into active cytokine.

PMID- 17032169
TI  - Attenuation of cytokine responsiveness during T cell development and
      differentiation.
AB  - Cytokines play critical roles during T cell development; however, it is unclear
      to what extent development is altered by the high levels of cytokines produced
      during immune responses. A potential mechanism to shield developing cells from
      cytokine influence is attenuation of cytokine signaling. Using intracellular
      staining and flow cytometry to detect cytokine-induced Stat phosphorylation, we
      analyzed the cytokine responsiveness of developmentally defined mouse T cells. We
      assessed CD4(-)CD8(-) (DN), CD4(+)CD8(+) (DP), CD4(+)CD8(-) (SP4), and CD4(
      )CD8(+) (SP8) in the thymus, and CD4(+)CD44(lo) (naive), CD4(+)CD44(hi) (memory),
      CD8(+)CD44(lo) (naive), and CD8(+)CD44(hi) (memory) in the periphery for
      responsiveness to interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL- 10, IL-15,
      interferon-alpha (IFN-alpha), and IFN-gamma. SP thymocytes responded to a wider
      range of cytokines than did the less mature DN and DP subpopulations. DP
      thymocytes were nonresponsive to all cytokines tested except for modest responses
      to IL-4 and IFN-alpha. Peripheral naive and memory T cells also displayed
      differential cytokine sensitivity. Memory T cells were less responsive to the
      proinflammatory cytokines IL-6 and IFN-gamma when compared with naive T cells,
      and the memory CD4(+) subset was less responsive to IL-4. In summary, developing
      thymocytes and memory T cells appear to be resistant to the influences of
      numerous cytokines produced during immune responses.

PMID- 17032170
TI  - Mechanism of direct hepatotoxic effect of KC chemokine: sequential activation of
      gene expression and progression from inflammation to necrosis.
AB  - This work aimed to show that an important, yet unrecognized, role of KC chemokine
      in the liver is regulation of gene expression. KC expression in the liver
      stimulated three classes of genes in this temporal order: immediate-early genes,
      proinflammatory genes, and profibrotic genes. Transcription factors E2F5 and
      early growth response 1 (EGR1), Ca(2+) signaling molecules S100A8 and S100A9, and
      two oxidative stress-induced genes were identified as immediate-early genes of
      KC. Expression of these genes was stimulated at 3-5-fold increased KC
      concentrations. Expression of proinflammatory genes was activated 6 h after the
      immediateearly genes, and they included interleukin-1alpha (IL-1alpha) and IL
      1beta. KC receptor gene CXCR2 was also upregulated, suggesting that KC may act
      through a positive feedback loop. Stimulation of expression of profibrotic genes,
      including type I collagen, was seen only after the proinflammatory genes were
      highly expressed for 12 h. KC is a potent regulator of gene expression that
      proceeds in a sequential manner. Immediate-early genes of KC stimulation were
      identified. The positive feedback regulation and an increased oxidative stress
      induced by KC may explain the poor prognosis in liver patients with elevated
      levels of CXC chemokines.

PMID- 17032171
TI  - Intestinal permeability and cytokine inflammatory response in multiply injured
      patients.
AB  - In experimental settings, the increased intestinal permeability (IP) following
      severe trauma is associated with increased serum concentrations of cytokines.
      Multiply injured patients are susceptible to the development of multiple organ
      failure (MOF). The aim of this study was to determine if altered IP after trauma
      was associated with upregulation of cytokines and if cytokines and IP influenced
      the development of MOF. In 30 multiply injured patients, IP was measured on days
      2 and 4 after injury using the lactulose-mannitol (L-M) test, and the levels of
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 were
      determined simultaneously. The L-M ratio increased significantly from 0.049
      (0.017-0.133) on day 2 to 0.150 (0.059-0.339) on day 4 (p < 0.02) On day 4, a
      significant correlation was also found between the L-M ratio and IL-6 (r = 0.43,
      p < 0.03). The IL-6 level on days 2 and 4 was significantly (p < 0.01 and p <
      0.03, respectively) higher in MOF patients than in those without MOF, as was the
      TNF-alpha level on day 4 significantly higher (p < 0.04) in MOF patients. IP
      increases following multiple trauma, and on day 4 it correlates with the IL-6
      level. However, in patients who develop MOF only cytokines are invariably
      increased, with IL-6 alone being significantly increased on both measurements in
      these patients.

PMID- 17032173
TI  - A physiological role of AMP-activated protein kinase in phenobarbital-mediated
      constitutive androstane receptor activation and CYP2B induction.
AB  - CAR (constitutive androstane receptor) is a nuclear receptor that regulates the
      transcription of target genes, including CYP (cytochrome P450) 2B and 3A. The
      transactivation by CAR is regulated by its subcellular localization; however, the
      mechanism that governs nuclear translocation has yet to be clarified. It has been
      reported recently that AMPK (AMP-activated protein kinase) is involved in
      phenobarbital-mediated CYP2B induction in a particular culture system. We
      therefore investigated in vivo whether AMPK is involved in the activation of CAR
      dependent gene expression. Immunoblot analysis using an antibody which recognizes
      Thr-172-phosphorylated AMPKalpha1/2 revealed phenobarbital-induced AMPK
      activation in rat and mouse livers as well. Phenobarbital, however, failed to
      increase the liver phospho-AMPK level of tumour-bearing rats in which CAR nuclear
      translocation had been impaired. In in vivo reporter gene assays employing PBREM
      (phenobarbital-responsive enhancer module) from CYP2B1, an AMPK inhibitor 8-bromo
      AMP abolished phenobarbital-induced transactivation. In addition, Cyp2b10 gene
      expression was attenuated by 8-bromo-AMP. Forced expression of a dominant
      negative mutant and the wild-type of AMPKalpha2 in the mouse liver suppressed and
      further enhanced phenobarbital-induced PBREM-reporter activity respectively.
      Moreover, the AMPK activator AICAR (5-amino-4-imidazolecarboxamide riboside)
      induced PBREM transactivation and an accumulation of CAR in the nuclear fraction
      of the mouse liver. However, AICAR and metformin, another AMPK activator, failed
      to induce hepatic CYP2B in mice and rats. These observations suggest that AMPK is
      at least partly involved in phenobarbital-originated signalling, but the kinase
      activation by itself is not sufficient for CYP2B induction in vivo.

PMID- 17032174
TI  - Regulation of ceruloplasmin in human hepatic cells by redox active copper:
      identification of a novel AP-1 site in the ceruloplasmin gene.
AB  - Cp (ceruloplasmin), a copper containing plasma protein, mainly synthesized in the
      liver, is known to be functional between the interface of iron and copper
      metabolism. We have reported previously that Cp is regulated by cellular iron
      status, but the process of the regulation of Cp by copper still remains a subject
      for investigation. In the present paper, we show that PDTC (pyrrolidine
      dithiocarbamate), a thiol compound widely known to increase intracellular redox
      copper, regulates Cp expression in hepatic cells by a copper-dependent
      transcriptional mechanism. To find out the mechanism of induction, chimeric
      constructs of the Cp 5'-flanking region driving luciferase were transfected into
      human hepatic cells. Deletion and mutational analyses showed the requirement of a
      novel APRE [AP-1 (activator protein-1) responsive element] present about 3.7 kb
      upstream of the translation initiation site. The role of AP-1 was confirmed by
      electrophoretic mobility-shift analysis. Western blot and overexpression studies
      detected the AP-1 as a heterodimer of c-jun and c-fos proteins. The activation of
      AP-1 was found to be copper-dependent as a specific extracellular chelator
      bathocuproine disulfonic acid blocked PDTC-mediated induction of AP-1-DNA binding
      and increased reporter gene activity. Whereas, in a copper-free medium, PDTC
      failed to activate either AP-1 or Cp synthesis, supplementation of copper could
      reverse AP-1 activation and Cp synthesis. Our finding is not only the first
      demonstration of regulation of Cp by redox copper but may also explain previous
      findings of increased Cp expression in cancers like hepatocarcinoma, where the
      intracellular copper level is higher in a redox compromised environment.

PMID- 17032175
TI  - Positron emission tomography/computed tomography: diagnostic accuracy in
      lymphoma.
AB  - An accurate initial staging of patients with non-Hodgkin lymphoma (NHL) and
      Hodgkin lymphoma (HL) is critical for the selection of an appropriate treatment.
      Computed tomography (CT) remains the standard imaging technique, although it is
      based on anatomic criteria. Positron emission tomography (PET) with 2-deoxy-2
      [fluorine-18]fluoro-d-glucose (FDG) provides useful functional information but
      requires anatomical correlation to localise lesions accurately. We have
      prospectively compared the accuracy of combined PET/CT with that of CT and PET
      alone at initial staging in lymphoma patients. Forty-seven newly diagnosed
      patients were evaluated. PET/CT was superior compared with CT and PET in nodal
      evaluation and detection of extranodal disease. Using a staging algorithm with
      PET/CT resulted in the disease stage being increased in 11 of 47 patients (10 NHL
      and 1 HL) (McNemar test P = 0.012). Therefore, a different treatment strategy
      based on PET/CT findings was suggested for seven patients (14.8%). PET/CT
      markedly improves accuracy in the diagnostic work-up of patients with lymphoma.

PMID- 17032176
TI  - Outcome in patients with Wiskott-Aldrich syndrome following stem cell
      transplantation: an analysis of 57 patients in Japan.
AB  - A total of 57 patients with Wiskott-Aldrich syndrome (WAS) were studied after
      undergoing stem cell transplantation (SCT) in Japan between January 1985 and
      December 2004. Eleven patients received transplants from human leucocyte antigen
      (HLA)-matched related donors, 10 from HLA-mismatched related donors, 21 from
      unrelated bone marrow donors, and 15 from unrelated cord blood donors. Nine of
      the 57 patients rejected the initial graft. The overall 5-year survival rate was
      73.7% and the 5-year failure-free survival rate was 65.7% (failure was defined as
      rejection or death). The overall 5-year survival rates for patients receiving
      bone marrow and cord blood from unrelated donors were both 80.0%. Based on
      univariate analysis, the factors associated with poor survival were:
      transplantation from an HLA-mismatched related donor, patient age of more than 5
      years at the time of transplantation, and a conditioning regimen other than
      busulfan and cyclophosphamide (BU-CY) or busulfan, cyclophosphamide and
      antithymocyte globulin (BU-CY-ATG). In a multivariate analysis, a conditioning
      regimen other than BU-CY and BU-CY-ATG was the only independent factor associated
      with transplantation failure. Given the improved outcome for WAS patients
      following transplantation from an unrelated donor, we conclude that patients with
      WAS should receive SCT as soon as possible after diagnosis.

PMID- 17032177
TI  - Pure red cell aplasia associated with thymoma: clinical insights from a 50-year
      single-institution experience.
AB  - Acquired pure red cell aplasia (PRCA) is a rare disorder of erythropoiesis that
      can develop in association with a thymoma. Optimal management of this subgroup is
      unclear, and there have been few series reporting long-term clinical outcomes.
      Here, we report features of 13 patients treated for PRCA associated with thymoma
      over 50 years at our institution. Surgical resection of the thymoma was
      insufficient for normalisation of erythropoiesis in all cases. T-cell gene
      rearrangement studies did not routinely demonstrate a clonal process, and
      ciclosporin and anti-thymocyte globulin were effective adjuvant treatments.
      However, treatment-related morbidity was high, with frequent infectious
      complications.

PMID- 17032178
TI  - Pro: esophagectomy is the treatment of choice for high-grade dysplasia in
      Barrett's esophagus.

PMID- 17032179
TI  - CON: surgery for Barrett's with flat HGD-no!

PMID- 17032180
TI  - A balancing view: an individualized approach to high-grade dysplasia is key:
      esophagectomy, surveillance, or endoscopic therapy should all be considered.

PMID- 17032181
TI  - Perils and pitfalls of small negative clinical trials.

PMID- 17032182
TI  - Barrett's esophagus at a tertiary care center: association of age on incidence
      and prevalence of dysplasia and adenocarcinoma.
AB  - OBJECTIVES: Barrett's esophagus (BE) is traditionally thought of as a disease of
      middle-aged Caucasian men. Little is known about BE in younger patients. We
      sought to assess the effect of age on features of BE including the prevalence and
      incidence of dysplasia and carcinoma. METHODS: All patients enrolled into the
      Cleveland Clinic BE registry from 1979 to 2002 were studied. Age, ethnicity,
      number of endoscopies, hiatal hernia size, length of Barrett's segment,
      prevalence and incidence of dysplasia, and cancer were compared between patients
      > or = 50 yr old and < 50 yr old. RESULTS: There were 837 patients in the
      registry (638 > or = 50 yr, 199 < 50 yr). Hiatal hernia size was larger in
      patients > or = 50 yr than in those < 50 yr (median 4.0 cm, interquartile range
      2.0-5.0 cm vs 3.0, 2.0-4.0 cm; p < 0.01). Otherwise, there were no significant
      differences among other features in the patient population. There were 225
      patients with dysplasia or cancer (195 > or = 50 yr and 30 < 50 yr; p < 0.01). Of
      this group, 176 were prevalent cases (159 > or = 50 yr and 17 < 50 yr) and 49
      were incident cases (36 > or = 50 yr and 13 < 50 yr). The odds of those > or = 50
      yr being a prevalent case of high-grade dysplasia or cancer was five times the
      odds of those < 50 yr (p < 0.01). The incidence of dysplasia or cancer was
      similar in both age groups. CONCLUSIONS: Our study supports emerging data that
      approximately 25% of BE patients are less than 50 yr of age. While older patients
      had a higher prevalence of dysplasia or adenocarcinoma, the incidence of
      dysplasia and adenocarcinoma is similar in both age groups. Future screening
      strategies for BE should recognize these important findings.

PMID- 17032183
TI  - Predictors of endoscopic findings after Roux-en-Y gastric bypass.
AB  - OBJECTIVES: To evaluate predictors of endoscopic findings in symptomatic patients
      after Roux-en-Y gastric bypass (RYGBP) for obesity. METHODS: A retrospective
      chart review of 1,001 RYGBP procedures was performed. Two hundred twenty-six
      (23%) patients were identified as having endoscopy to evaluate upper
      gastrointestinal symptoms following surgery. Polychotomous logistic regression
      analysis was used to assess predictors of normal endoscopy, marginal ulcers,
      stomal stenosis, and staple-line dehiscence. RESULTS: The most common endoscopic
      findings were 99 (44%) normal postsurgical anatomy, 81 (36%) marginal ulcer, 29
      (13%) stomal stenosis, and 8 (4%) staple-line dehiscence. Factors that
      significantly increase the risk of marginal ulcers following surgery include
      smoking (AOR = 30.6, 95% CI 6.4-146) and NSAID use (AOR = 11.5, 95% CI 4.8-28).
      PPI therapy following surgery was protective against marginal ulcers (AOR = 0.33,
      95% CI 0.11-0.97). Median time for diagnosis of marginal ulcers following surgery
      was 2 months, and 77 of 81 (95%) presented within 12 months. CONCLUSIONS:
      Following RYGBP surgery for obesity, smoking and NSAID use significantly increase
      the risk of marginal ulceration, and PPI therapy is protective. Because a
      significant majority of marginal ulcers present within 12 months of surgery, it
      may be reasonable to consider prophylactic PPI therapy during this time period,
      especially for high risk patients.

PMID- 17032184
TI  - Stress ulcer prophylaxis in non-critically ill patients: less may be more.
AB  - Significant upper gastrointestinal bleeding resulting from stress ulceration is a
      serious life-threatening complication. However, it occurs relatively rarely even
      in the sickest patients. Therefore, guidelines suggest that prophylaxis (e.g.,
      with acid-suppressive therapy) should be reserved for highly selected patients.
      Despite these recommendations, numerous studies suggest that many hospitalized
      patients are inappropriately placed on acid-suppressive therapy (AST) for the
      sole purpose of preventing stress ulceration. Moreover, it appears that once AST
      is started, medications are continued even after discharge, resulting in further
      unnecessary expenditure of resources. National and local efforts are needed to
      curtail this practice that places patients at risk for drug side effects while
      affording them little or no benefit.

PMID- 17032185
TI  - Propofol alone titrated to deep sedation versus propofol in combination with
      opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy.
AB  - BACKGROUND: Propofol by nonanesthesiologists is controversial because the drug is
      commonly used to produce deep sedation or general anesthesia. Propofol in
      combination with opioids and/or benzodiazepines can be titrated to moderate
      sedation, which might be safer. AIM: To compare recovery time, patient
      satisfaction, and other end points with propofol alone titrated to deep sedation
      versus propofol combination therapy with opioids and/or benzodiazepines. METHOD:
      A randomized controlled clinical trial of propofol alone titrated to deep
      sedation versus fentanyl plus propofol versus midazolam plus propofol versus
      fentanyl plus midazolam plus propofol in 200 outpatients undergoing colonoscopy.
      Each combination regimen was titrated to moderate sedation. RESULTS: Patients
      receiving propofol alone received higher doses of propofol and had deeper
      sedation scores compared with combination therapy (both p < 0.001). Patients
      receiving combination regimens were discharged more quickly (median 13.0-14.7
      versus 18.1 min) than those receiving propofol alone (p < 0.01). There were no
      differences in vital signs or oxygen saturations among the study arms. There were
      no significant differences in pain or satisfaction among the study arms in the
      recovery area. At a follow-up phone call, patients receiving fentanyl and
      propofol remembered more of the procedure than those in the other regimens (p <
      0.005) and remembered more pain than those receiving propofol alone (p < 0.02).
      CONCLUSIONS: Propofol in combination with fentanyl and/or midazolam can be
      titrated to moderate levels of sedation without substantial loss of satisfaction
      and with shorter recovery times compared with propofol titrated to deep sedation
      throughout the procedure.

PMID- 17032186
TI  - The impact of endoscopic ultrasound and computed tomography on the TNM staging of
      early cancer in Barrett's esophagus.
AB  - INTRODUCTION: Computed tomography (CT) and endoscopic ultrasound (EUS) are part
      of the regular staging protocol in esophageal cancer. The value of the two
      methods was assessed in patients with early cancer in Barrett's esophagus.
      METHODS: One hundred consecutive patients (median age 64 yr, interquartile range
      [IQR] 58-72) with suspected early cancer in Barrett's esophagus who were referred
      to our hospital for endoscopic therapy were prospectively included in a
      standardized staging program with upper gastrointestinal endoscopy, EUS (7.5 MHz
      in all cases plus 12.5 or 20 MHz for elevated and/or depressed lesions), CT of
      the chest and upper abdomen, and abdominal ultrasonography. The results were
      summarized in accordance with the TNM classification. On the basis of the lymph
      node findings on CT and/or EUS, the patients were assigned to three categories:
      C1, no suspicious lymph nodes; C2, paraesophageal lymph nodes < or =1 cm in size
      at the tumor level, lymph nodes > or =1 cm in size not at the tumor level in the
      mediastinum or celiac trunk; and C3, paraesophageal lymph nodes > 1 cm in size at
      the tumor level. The EUS and CT findings were checked every 6 months in patients
      who underwent endoscopic treatment. Surgical resection was scheduled in operable
      patients if staging showed a T category higher than T1 and/or the lymph node
      staging was assessed as C3. Patients with suspected submucosal infiltration
      underwent diagnostic endoscopic resection, and if submucosal involvement was
      confirmed were referred for surgery. RESULTS: The median follow-up period was 25
      months (IQR 19.5-30.0). The T category diagnosed with CT was < or = T1 in all
      patients. On EUS, the T category was classified as T1 in 92% of cases (N = 92)
      and as > T1 in 8% (N = 8, p < 0.05). Enlarged lymph nodes (C2 and C3) were
      detected in 45% of the patients. Significantly more C2 lymph nodes were diagnosed
      with EUS than CT (28 vs 19, p < 0.05). Lymph nodes at the level with the highest
      suspicion, C3, were detected using CT in only three of nine cases. Sensitivity of
      CT for N staging was not acceptable compared with EUS (38%vs 75%). No extranodal
      metastases were found on CT. CONCLUSIONS: In suspected early cancer in Barrett's
      esophagus, EUS is superior to CT for T staging and N staging. As CT had no
      influence on the TNM classification in any of these patients, it may be possible
      to dispense with this method as a staging procedure in patients with cancer in
      Barrett's esophagus. By contrast, EUS is required in order to differentiate
      between patients with cancer in Barrett's esophagus in whom endoscopic therapy is
      suitable and those in whom surgical treatment is required.

PMID- 17032187
TI  - Diagnosis and outcome of small bowel tumors found by capsule endoscopy: a three
      center Australian experience.
AB  - OBJECTIVE: The objective of the study was to examine diagnosis and outcome in a
      series of patients with small bowel tumors detected by capsule endoscopy (CE) in
      three Australian centers. METHODS: Review of prospectively collected data from
      416 CEs identified 27 tumors in 26 patients. Clinical parameters, tumor
      histology, and follow-up are reported. RESULTS: Twenty-seven tumors were
      identified in 26 patients (mean age 61 +/- 13.7 yr). Indications for CE were
      obscure gastrointestinal (GI) bleeding (21), suspected tumor (3), abdominal pain
      (1), diarrhea (1). Prior radiology found a possible lesion in 8 of 23 (35%). Nine
      tumors were proven benign: hamartoma (4), cystic lymphangioma (1), primary
      amyloid (1), lipoma (1). Two lesions were non-neoplastic: heterotopic gastric
      mucosa and inflammatory fibroid polyp. Seventeen tumors were malignant: five
      adenocarcinomas, six carcinoids, two melanoma metastases, two gastrointestinal
      stromal tumors (GIST), one colon carcinoma metastasis, one non-Hodgkin's
      lymphoma. Tumors were surgically resected in 23 patients. Resection was
      considered curative in 12 (52%). Mean duration of follow-up was 26 +/- 13.7
      months. Of the five patients with primary adenocarcinoma only one remains disease
      free. Three of the six with carcinoid tumors have had no recurrence up to 51
      months postresection. Both patients with GIST are disease free. Anemia resolved
      after surgery in the patients with melanoma. CONCLUSIONS: Small bowel tumors are
      a significant finding at CE and are often missed by other methods of
      investigation. In many patients, detection of a tumor alters management and
      improves outcome. Even in malignant lesions, treatment is potentially curative in
      the absence of metastatic disease.

PMID- 17032188
TI  - Higher prevalence and severity of hepatic encephalopathy in patients with HCV
      cirrhosis and diabetes mellitus: is presence of autonomic neuropathy the missing
      part of the puzzle?
AB  - Hepatic encephalopathy (HE) is a complex and variable neuropsychiatric syndrome
      that is seen in patients with acute and chronic liver diseases. The presence or
      severity of HE does not always show a strong and consistent relationship with the
      severity of liver disease or portal hypertension suggesting that other
      predisposing or precipitating factors may be involved. In this issue of the
      journal, it has been suggested that DM may contribute to the presence and
      severity of HE independent of the severity of liver disease in patients with HCV
      cirrhosis. This editorial examines the limitations of the study and potential
      mechanisms that could explain the relationship between DM with HE including the
      role of autonomic neuropathy.

PMID- 17032189
TI  - Metabolic syndrome is associated with greater histologic severity, higher
      carbohydrate, and lower fat diet in patients with NAFLD.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic
      manifestation of metabolic syndrome. Insulin resistance (IR) is a key component
      of metabolic syndrome. The aim was to determine the dietary composition, physical
      activity, and histologic severity between NAFLD patients with and without
      metabolic syndrome. METHODS: Ninety-one patients with NAFLD completed the Block
      Food Frequency Questionnaire and the Paffenbarger Physical Activity
      Questionnaire. IR was assessed by the homeostasis model assessment (HOMA) index.
      Metabolic syndrome was defined by the ATP III clinical definition. Nonalcoholic
      steatohepatitis (NASH) Clinical Network Scoring System was used to determine the
      histologic severity of NAFLD. RESULTS: Thirty-one patients (34%) had metabolic
      syndrome. Patients with metabolic syndrome had a higher HOMA index (7.66 vs 4.45,
      p = 0.04), and consumed more carbohydrates (51%vs 45%, p = 0.03) and less fat
      (34%vs 40%, p = 0.01) compared with those without metabolic syndrome; total daily
      calorie, protein consumption, and physical activity were similar between the two
      groups. Patients with metabolic syndrome had higher scores for steatosis (2.0 +/-
      0.8 vs 1.37 +/- 1, p = 0.02), NASH activity (4.13 +/- 1.4 vs 3.13 +/- 1.7, p =
      0.004), and global NASH score (5.9 +/- 1.7 vs 4.4 +/- 2.3, p = 0.0006) compared
      with those without metabolic syndrome. When controlled for other factors
      including dietary composition and physical activity, the presence of metabolic
      syndrome was a significant risk factor for global NASH severity in addition to
      HOMA index and female gender. CONCLUSION: Metabolic syndrome in patients with
      NAFLD is associated with a diet containing more carbohydrate and less fat and
      greater histologic severity. The role of a carbohydrate-restricted diet in
      decreasing the risk for metabolic syndrome and histologic severity should be
      assessed in patients with NAFLD.

PMID- 17032190
TI  - Integrated psychiatric/medical care in a chronic hepatitis C clinic: effect on
      antiviral treatment evaluation and outcomes.
AB  - OBJECTIVES: Psychiatric and substance use disorders are common in hepatitis C
      patients and represent barriers to antiviral treatment. We evaluated the effect
      of integrating psychiatric and medical care on evaluation for and initiation of
      antiviral treatment in a cohort of 184 patients with chronic hepatitis C.
      METHODS: Integrated care consisted of screening for psychiatric problems with
      Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), Beck Depression
      Inventory (BDI), Urine Drug Screen (UDS), and Primary Care Posttraumatic Stress
      Disorder (PC-PTSD) screens, referral based on specified cutoff scores to an
      established mental health (MH) provider, to a colocated psychiatric clinical
      nurse specialist (PCNS), or both. Data were collected retrospectively by chart
      review. RESULTS: Most patients (149/184, 81.0%) had at least one positive screen,
      25.5% had a positive UDS. Among patients with positive screens, 38.3% had
      established MH providers, 47.0% had no MH provider and were referred to the PCNS,
      and 15.0% refused any psychiatric referral. Patients receiving integrated care
      with a colocated PCNS were significantly more likely to complete evaluation for
      and start antiviral treatment than other patients with positive screens, and at a
      rate similar to that of patients with negative screens. Patients with positive
      screens followed by any MH provider had significantly greater adherence to
      antiviral therapy than patients without positive screens. CONCLUSION: An
      integrated MH and medical approach was associated with rates of antiviral therapy
      recommendation and initiation similar to patients without risks for psychiatric
      or substance use problems. MH care was associated with improved adherence to
      antiviral therapy. Integrated care offers promise as an approach for addressing
      psychiatric comorbidity in this traditionally difficult to treat population.

PMID- 17032191
TI  - Risk factors for gallstone-related hospitalization during pregnancy and the
      postpartum.
AB  - OBJECTIVES: Gallbladder disease is a leading nonobstetrical cause for
      hospitalization in the first year postpartum. The aim of this study was to define
      the incidence and risk factors for postpartum hospitalization as a result of
      gallstone-related disease. METHODS: We identified 6,670 women with discharge
      diagnoses related to biliary disease from linked birth certificate and hospital
      discharge databases for Washington State from 1987 through 2001. Cases were women
      with gallstone-related diagnoses at delivery or as primary diagnosis in the
      postpartum. Four controls who were within 1 yr postpartum were randomly selected
      for each case and matched for year of delivery. From the birth certificates, we
      obtained data about patient demographics, reproductive history, and pregnancy
      related risk factors. In a retrospective case-control study, we developed
      multiple logistic regression models to identify independent risk factors for
      hospitalization. RESULTS: We identified 6,211 women as cases (0.5% of all births)
      during the study period. The median time to hospitalization was 95 days
      (interquartile range 46-191 days), with a median length of stay of 3 days.
      Seventy-six percent were diagnosed with uncomplicated cholelithiasis, 16% with
      pancreatitis, 9% with acute cholecystitis, and 8% with cholangitis. Seventy-three
      percent of hospitalized women underwent cholecystectomy, and 5% underwent
      endoscopic retrograde cholangiopancreatography (ERCP). On multivariate analysis,
      independent risk factors for hospitalization included maternal race, age, being
      overweight or obese prepregnancy, pregnancy weight gain, and estimated
      gestational age. CONCLUSIONS: Hospitalization for gallstone-related disease is
      common in the first year postpartum, most commonly for uncomplicated
      cholelithiasis. Risk factors for hospitalization include prepregnancy body mass
      index, race, Hispanic ethnicity, and maternal age.

PMID- 17032192
TI  - Antiviral therapy decreases hepatic venous pressure gradient in patients with
      chronic hepatitis C and advanced fibrosis.
AB  - BACKGROUND: Antiviral therapy (AVT) may improve liver histology in patients with
      advanced viral hepatitis but its effect on portal pressure remains unknown. AIM:
      This study was aimed to evaluate the influence of antiviral therapy (AVT) on
      hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients
      with portal hypertension. METHODS: Twenty compensated patients with chronic
      hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b
      plus ribavirin. Every patient underwent liver biopsy and portal pressure
      measurements before and immediately after AT. Biopsies were evaluated according
      to METAVIR score. RESULTS: HVPG significantly dropped in all but one treated
      patient, with a mean (SD) reduction of 28.2 (12)%[13.8 (5.6) Vs. 10.2 (3.8) mmHg,
      p = 0.005]. The percentage of HVPG decrease was significantly greater in patients
      who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7
      (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade
      of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients
      with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or
      under the 12 mmHg threshold (6/11). CONCLUSIONS: AVT reduces HVPG in compensated
      patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal
      hypertension.

PMID- 17032194
TI  - Outcome of surgical versus percutaneous drainage of abdominal and pelvic
      abscesses in Crohn's disease.
AB  - OBJECTIVE: Abdominal and pelvic abscesses are a common complication of Crohn's
      disease. We studied the effect of the initial choice of therapy on time to
      resolution of abdominal and pelvic abscesses. METHODS: We recorded clinical,
      laboratory, and radiographic data on all adult patients with Crohn's disease and
      abdominal or pelvic abscesses treated at our institution from 1991 to 2001 and
      followed > or = 1 yr. Univariate analysis identified variables associated with
      initial choice of drainage modality. These variables were included in a Cox
      regression model to identify factors independently associated with time to
      resolution. RESULTS: Of 66 episodes identified, surgery was the initial modality
      in 29 and percutaneous drainage in 37. Median time to resolution was not
      different between surgical drainage (25.0 days, range 0-240) and percutaneous
      drainage (21.5 days, range 0-182) (p = 0.084). Older age, longer duration of
      symptoms prior to drainage, no fistula identified radiographically, immune
      modulator use, no rebound tenderness, and admission to the medical service were
      factors associated with percutaneous drainage as initial modality. These factors,
      when incorporated in a Cox regression model, did not significantly affect the
      time to resolution. Days from onset of symptoms to radiographic diagnosis or
      drainage were independently associated with time to resolution of the abscess.
      CONCLUSION: Time to resolution of abdominal or pelvic abscesses in Crohn's
      disease is similar with percutaneous drainage and surgery. One-third of patients
      treated with percutaneous drainage required surgery within 1 yr. Earlier
      intervention for abdominal and pelvic abscesses is associated with shorter time
      to resolution.

PMID- 17032193
TI  - Erythropoietin treatment is associated with more severe thrombocytopenia in
      patients with chronic hepatitis C undergoing antiviral therapy.
AB  - BACKGROUND: Erythropoietin (EPO) not only stimulates erythropoiesis but also
      thrombopoiesis. As pegylated-interferon-alpha(PEG-IFN-alpha)-induced
      thrombocytopenia may become a limiting factor for continuation of therapy, the
      present study investigated if EPO can alleviate PEG-IFN-alpha induced
      thrombocytopenia. Further, we hypothesize that EPO increases platelet reactivity
      and protease activated receptor 1 (PAR-1) expression during combination antiviral
      therapy. METHODS: Forty patients with chronic hepatitis C received either 10,000
      IU EPO 3 x/week or placebo in a randomized, placebo-controlled, double-blinded
      fashion for 4 wk and combination antiviral therapy with PEG-IFN-2a and ribavirin.
      RESULTS: EPO alleviated the decrease in hemoglobin during combination antiviral
      therapy with ribavirin (10%vs 20%, p < 0.0001). Platelet counts decreased
      stronger in EPO than in placebo group on day 28 (p= 0.007). EPO induced a 40%
      increase in PAR-1 (p < 0.0001), which was accompanied by 100% increase in
      platelet reactivity (p < 0.0001). PFA-100 platelet plug formation time and PEG
      IFN-alpha-induced vWF-increase were not different between study groups.
      CONCLUSIONS: Treatment with EPO alleviated the decrease in hemoglobin but
      worsened PEG-IFN-alpha induced thrombocytopenia after the first 4 wk of
      combination therapy. EPO caused PAR-1 receptor upregulation on platelets, which
      promoted an increase in platelet reactivity without affecting PFA-100 platelet
      plug formation time. EPO is not a useful option for short-term support of
      platelet production during antiviral therapy.

PMID- 17032195
TI  - Bowel dysfunction in patients with motor complete spinal cord injury: clinical,
      neurological, and pathophysiological associations.
AB  - BACKGROUND: Abnormal bowel function is a key problem in patients with spinal cord
      injury (SCI). Previous works provided only partial information on colonic transit
      time (CTT) or anal dysfunction but did not identified a comprehensive neurogenic
      bowel pattern. AIM: To evaluate clinical, neurological, and pathophysiological
      counterparts of neurogenic bowel in patients with motor complete SCI. METHODS:
      Fifty-four patients (56% men, mean age 35 yr) with chronic motor complete SCI
      (mean evolution time 6 yr) were evaluated: 41% with injuries above T7 (> T7) and
      59% with injuries below T7 (< T7); patients were also classified according to the
      presence or not of sacral spinal reflexes. Clinical assessment, total and
      segmental CTT quantification, anorectal function evaluation by manometry,
      intrarectal balloon distension, and surface electromyography were performed.
      RESULTS: Three different neuropathophysiological patterns were observed: Pattern
      A, present in > T7 injuries, characterized by very frequent constipation (86%)
      with significant defecatory difficulty and not very severe incontinence (Mean
      Wexner score 4.5); it was related to moderate delay in CTT (mainly in the left
      colon and recto-sigma), incapacity to increase the intra-abdominal pressure, and
      the absence of anal relaxation during the defecatory maneuvre; Pattern B, present
      in < T7 injuries with preserved sacral reflexes, characterized by not so frequent
      constipation (50%) but very significant defecatory difficulty and not very severe
      incontinence (Wexner 4.8); the pathophysiological counterpart was a moderate
      delay in CTT, capacity to increase intra-abdominal pressure, increased anal
      resistance during the defecatory maneuver, and presence of external anal
      sphincter (EAS) contraction when intra-abdominal pressure increased and during
      rectal distension; Pattern C, present in < T7 injuries without sacral reflexes,
      characterized by not very frequent constipation (56%) with less defecatory
      difficulty and greater severity of incontinence (Wexner 7.2); this was associated
      with severe delay in CTT (mainly in the left colon), capacity to increase intra
      abdominal pressure, absence of anal resistance during the defecatory maneuver,
      and absence of EAS contraction when intra-abdominal pressure increased and during
      rectal distension. CONCLUSION: In patients with motor complete SCI, we were able
      to define three different neuropathophysiological patterns that are associated
      with bowel function abnormalities and clinical complaints; this might be of help
      when designing therapeutic strategies.

PMID- 17032196
TI  - Patterns of care for adjuvant therapy in a random population-based sample of
      patients diagnosed with colorectal cancer.
AB  - OBJECTIVES: Over the past decade, clinical trials have proved the efficacy of
      treatments for colorectal cancer (CRC). This study tracks dissemination of these
      treatments for patients diagnosed with stage II and III disease and compares risk
      of death for those who received guideline therapy to those who did not. METHODS:
      We conducted a stratified randomly sampled, population-based study of CRC
      treatment trends in the United States. Multivariate models were used to explore
      patient characteristics associated with receipt of treatments. We pooled data
      with a previous study-patients diagnosed in 1987-1991 and 1995. Cox proportional
      hazards models were used to assess observed cause-specific and all-cause
      mortality. RESULTS: In 2000, guideline therapy receipt decreased among stage III
      rectal cancer patients, but increased for stage III colon and stage II rectal
      cancer patients. As age increased, likelihood of receiving guideline treatment
      decreased (p < 0.0001). Overall, race/ethnicity was significantly associated with
      guideline therapy (p = 0.04). Rectal patients were less likely to have received
      guideline treatment. Consistent with randomized clinical trial findings, all
      cause mortality was lower in patients who received guideline therapy, regardless
      of Charlson comorbidity score. CONCLUSIONS: Mortality was decreased in patients
      receiving guideline therapy. Although, rates of guideline-concordant therapy are
      low in community clinical practice, they are apparently increasing. Newer
      treatment (oxaliplatin, capecitabine) started to disseminate in 2000. Racial
      disparities, present in 1995, were not detected in 2000. Age disparities remain
      despite no evidence of greater chemotherapy-induced toxicity in the elderly. More
      equitable receipt of cancer treatment to all segments of the community will help
      to reduce mortality.

PMID- 17032197
TI  - MUC4-expressing pancreatic adenocarcinomas show elevated levels of both T1 and T2
      cytokines: potential pathobiologic implications.
AB  - OBJECTIVE: The human MUC4 mucin plays an important role in the pathogenesis of
      pancreatic cancer. Recently, we have demonstrated that MUC4 expression in
      pancreatic tumor cells is regulated by interferon-gamma (IFNgamma) and by
      retinoic acid via transforming growth factor beta 2 (TGFbeta-2). In the present
      study, we established the pathobiological association of various cytokines and
      MUC4 in pancreatic tumor tissues and tumor cell lines. METHODS: Using
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and/or
      immunohistochemical analyses, we examined the expression of MUC4, IFNgamma,
      TGFbetas, and several immunologically relevant cytokines in a panel of 11
      pancreatic adenocarcinomas (PA), three normal pancreatic (NP) tissue specimens,
      and 11 pancreatic tumor cell lines. RESULTS: Our data revealed that both MUC4 and
      IFNgamma were expressed at moderate to high levels in the majority of PA, while
      being undetectable in NP. Moreover, transcript for interleukin 2 (IL-2), a known
      marker of activated T helper 1 (TH1) lymphocytes, exhibited an expression profile
      similar to IFNgamma, suggesting a role of these immune effector cells as a
      potential source of IFNgamma in PA. Of note, IFNgamma protein was detected in the
      inflamed tissues neighboring tumor areas. Furthermore, TGFbetas were expressed by
      most cell lines and frequently upregulated in PA compared with NP. Interestingly,
      both IL-12 and IL-10, two key cytokines of the TH1 and TH2 pathways,
      respectively, were expressed at higher levels in PA relative to NP. CONCLUSIONS:
      These observations support the potential implication of IFNgamma and TGFbetas in
      MUC4 regulation in vivo and suggest a complex interaction of TH1 and TH2
      signaling in the pancreatic tumor microenvironment. These findings may provide
      useful insights into the pathobiology of pancreatic cancer.

PMID- 17032198
TI  - Role of MUC genes and mucins in pancreatic neoplasia.

PMID- 17032199
TI  - Rotavirus infection frequency and risk of celiac disease autoimmunity in early
      childhood: a longitudinal study.
AB  - OBJECTIVE: Few studies have assessed the role of specific gastrointestinal
      infections in celiac disease. We investigated whether increased frequency of
      rotavirus infection, a common cause of gastrointestinal infection and
      inflammation, predicts increased risk of celiac disease autoimmunity. METHODS: A
      cohort of 1,931 children from the Denver metropolitan area who carried celiac
      disease human leukocyte antigen (HLA) risk alleles were followed from infancy for
      development of celiac disease autoimmunity, defined as positivity at two or more
      subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies
      measured using a radioimmunoassay with human recombinant tTG. Blood samples were
      obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus
      antibodies were assayed using an indirect enzyme immunoassay in serial serum
      samples from each case and two matched controls. Frequency of infections were
      estimated by the number of increases (> 2 assay coefficient of variation) in
      rotavirus antibody between clinic visits. RESULTS: Fifty-four cases developed
      celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an
      intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent
      rotavirus infections predicted a higher risk of celiac disease autoimmunity
      (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI]
      0.39-9.56, for one infection and rate ratio 3.76, 95% CI 0.76-18.7, for > or = 2
      infections, rate ratio for trend per increase in number of infections = 1.94, 95%
      CI 1.04-3.61, p = 0.037). The result was similar after adjustment for gender,
      ethnic group, maternal education, breast-feeding, day-care attendance, number of
      siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. CONCLUSIONS:
      This prospective study provides the first indication that a high frequency of
      rotavirus infections may increase the risk of celiac disease autoimmunity in
      childhood in genetically predisposed individuals.

PMID- 17032200
TI  - Clinicopathological features of focal nodular hyperplasia-like nodules in 130
      cirrhotic explant livers.
AB  - OBJECTIVES: Focal nodular hyperplasia-like nodules (FNH-like nodules) are focal
      lesions occurring in liver cirrhosis and are morphologically very similar to
      classical FNH in an otherwise normal liver. They are sometimes misdiagnosed as
      hepatocellular carcinoma (HCC) on imaging because both types of lesions show
      arterial-phase enhancement. Although the morphological, immunohistochemical, and
      imaging features of FNH-like nodules are well-known, their pathogenesis and role
      in hepatocarcinogenesis have not been studied in detail. Therefore, we performed
      a detailed pathological evaluation of 130 cirrhotic explant livers and correlated
      these data with the clinical features of the patients. METHODS: All cirrhotic
      explant livers were uniformly sliced at 5-mm intervals and all detected focal
      lesions were microscopically classified according to internationally accepted
      criteria. The obtained data regarding FNH-like nodules were then correlated with
      other pathological findings and with clinical data obtained during pretransplant
      evaluation and recorded in a database. RESULTS: FNH-like nodules were present in
      15% of patients and their small size (75% of cases < 1 cm) appears to preclude
      detection by imaging in almost all cases. The presence of esophageal varices and
      pretransplant treatment with chemoembolization were independently and
      significantly associated with the presence of FNH-like nodules. There were no
      associations between FNH-like nodules on the one hand and low-grade dysplastic
      nodules, high-grade dysplastic nodules, and HCCs on the other hand. CONCLUSIONS:
      The clinicopathological features of FNH-like nodules support the hypothesis that
      vascular alterations in liver cirrhosis play an important role in their
      pathogenesis and that FNH-like nodules do not have an increased risk of malignant
      transformation.

PMID- 17032201
TI  - Efficacy of enteral nutrition for the treatment of pancreatitis using standard
      enteral formula.
AB  - BACKGROUND AND AIMS: Elemental formula delivered distal to the ligament of Treitz
      has demonstrated efficacy in patients with pancreatitis, presumably by decreasing
      pancreatic stimulation. Few data exist on the use of standard enteral formula in
      such patients. This study describes the outcomes of pancreatitis patients managed
      with long-term standard enteral nutrition (EN). METHODS: One hundred twenty-six
      patients managed at the University of Virginia Health System with pancreatitis
      requiring nutritional support between August 2000 and June 2004 received a
      standard formula delivered distal to the ligament of Treitz and were followed
      prospectively to resolution of their disease process. Predictors of improvement
      in CT Severity Index, duration of EN, and length of hospital stay were
      identified. Changes in body weight and serum albumin were determined. RESULTS:
      Mean age was 50.8 +/- 15.2 yr (male, 83). Etiology included alcohol (46),
      gallstones (49), idiopathic (15), post-ERCP (7), drug (5), hyperlipidemia (3),
      and pancreas divisum (1). EN lasted a median of 18.9 (2.4 to 111.7) wk. Median CT
      Severity Index decreased from 4 to 2 (p < 0.001). Underweight patients gained 9.8
      lbs; overweight and obese patients lost 7.2 and 28.8 lbs, respectively. Albumin
      concentration increased from 3 to 3.8 g/dL (p < 0.001). CONCLUSIONS: Standard
      enteral formula is effective in the management of patients with complicated
      pancreatitis.

PMID- 17032202
TI  - Overweight in celiac disease: prevalence, clinical characteristics, and effect of
      a gluten-free diet.
AB  - BACKGROUND: It is well established that a minority of celiac patients present
      with "classic" symptoms due to malabsorption. However, few studies have focussed
      on the distribution of body mass index (BMI) in celiac populations and its
      relationship to clinical characteristics, or on its response to treatment.
      METHODS: We reviewed BMI measurements and other clinical and pathological
      characteristics from a database of 371 celiac patients diagnosed over a 10-yr
      period and seen by a single gastroenterologist. To assess response to gluten
      exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with
      serological support for dietary compliance. RESULTS: Mean BMI was 24.6 kg/m2
      (range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211
      (57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48
      (13% of all patients) in the obese range (BMI > or = 30.0). There was a
      significant association between low BMI and female gender, history of diarrhea,
      reduced hemoglobin concentration, reduced bone mineral density (BMD),
      osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients
      compliant with a gluten-free diet, 81% had gained weight after 2 yr, including
      82% of initially overweight patients. CONCLUSIONS: Few celiac patients are
      underweight at diagnosis and a large minority is overweight; these are less
      likely to present with classical features of diarrhea and reduced hemoglobin.
      Failed or delayed diagnosis of celiac disease may reflect lack of awareness of
      this large subgroup. The increase in weight of already overweight patients after
      dietary gluten exclusion is a potential cause of morbidity, and the gluten-free
      diet as conventionally prescribed needs to be modified accordingly.

PMID- 17032203
TI  - Management and treatment of hepatitis C viral infection: recommendations from the
      Department of Veterans Affairs Hepatitis C Resource Center program and the
      National Hepatitis C Program office.
AB  - Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the
      general U.S. population and 5-10% of veterans who use Department of Veterans
      Affairs medical services. Chronic HCV is clearly linked to the development of
      cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease requiring
      liver transplantation. The consequences of HCV infection constitute a significant
      disease burden and demonstrate the need for effective medical care. Treatment of
      chronic HCV is aimed at slowing disease progression, preventing complications of
      cirrhosis, reducing the risk of HCC, and treating extrahepatic complications of
      the virus. As part of a comprehensive approach to HCV management, antiviral
      therapy with peginterferon alfa combined with ribavirin is the current standard
      of care. Antiviral therapy should be provided to those individuals who meet
      criteria for treatment and who are at greatest risk for progressive liver
      disease. Many of these patients may have comorbid medical and psychiatric
      conditions, which may worsen while on antiviral therapy. Current antiviral
      regimens are associated with significant adverse effects that can lead to
      noncompliance, dose reduction, and treatment discontinuation. To overcome these
      barriers and to address these issues, it has become crucial to facilitate a
      multidisciplinary team who can respond to and provide HCV-specific care and
      treatment. Screening for HCV, preventing transmission, delaying disease
      progression, ensuring appropriate antiviral therapy, and managing treatment
      related adverse effects can improve patient quality of life, treatment adherence,
      and ultimately, improve patient outcomes.

PMID- 17032204
TI  - Practice guidelines in acute pancreatitis.

PMID- 17032205
TI  - Epidemiology of childhood constipation: a systematic review.
AB  - OBJECTIVE: A systematic review of the published literature was performed to
      assess the prevalence, incidence, natural history, and comorbid conditions of
      functional constipation in children. METHODS: Articles were identified through
      electronic searches in Medline, Embase, Cochrane Central Library, Cinhal and
      PsychInfo databases. Study selection criteria included: (1) epidemiology studies
      of general population, (2) on the prevalence of constipation without obvious
      organic etiology, (3) in children from 0 to 18 yr old, and (4) published in
      English and full manuscript form. RESULTS: Eighteen studies met our inclusion
      criteria. The prevalence of childhood constipation in the general population
      ranged from 0.7% to 29.6% (median 8.9; inter quartile range 5.3-17.4). The
      prevalence of constipation defined as defecation frequency of < 3/wk varied from
      0.7% to 29.6% (median 10.4; inter quartile range 1.3-21.3). Identified studies
      originated from North America (N = 4), South America (N = 2), Europe (N = 9), the
      Middle-East (N = 1), and Asia (N = 2). Variance of gender specific prevalence was
      reported in seven studies and five of seven studies reported no significant
      difference between boys and girls. The age group in which constipation is most
      common could not be assessed with certainty. Socioeconomic factors were not found
      to be associated with constipation. CONCLUSION: Childhood constipation is a
      common problem worldwide. Most studies report similar prevalence rates for boys
      and girls. Large epidemiologic studies with the use of generally accepted
      diagnostic criteria are needed to define the precise prevalence of constipation.

PMID- 17032207
TI  - "Does fecal occult blood testing really reduce mortality? A reanalysis of
      systematic review data." by Moayyedi P and Achkar E.

PMID- 17032208
TI  - Mistaking "life" (as we know it) for "disease".

PMID- 17032210
TI  - The low incidence of bacterial infections could be a protective factor against
      variceal bleeding per se in hemodynamic responders to propranolol.

PMID- 17032211
TI  - Regression of hepatocellular carcinoma due to cyclooxygenase (COX)-2 inhibitor.

PMID- 17032212
TI  - Magnetic resonance imaging meets immunology: an unusual combination of diagnostic
      tools leads to the diagnosis actinomycosis.

PMID- 17032213
TI  - Small cell carcinoma of the large bowel: a rare, but very aggressive malignancy.

PMID- 17032214
TI  - Pneumatic dilatations for achalasia: a safe and effective choice for most
      patients.

PMID- 17032218
TI  - Inhibition of aflatoxin B production of Aspergillus flavus, isolated from soybean
      seeds by certain natural plant products.
AB  - AIMS: The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania
      somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus
      sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and
      spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin B(1)
      production by toxigenic strain of Aspergillus flavus isolated from soybean seeds
      was investigated. METHODS AND RESULTS: Soybean seed was treated with different
      natural products and fungicide captan and was inoculated with toxigenic strain of
      A. flavus and incubated for different periods. The results showed that all the
      treatments were effective in controlling aflatoxin B(1) production. Captan, neem
      cake, spore suspension of T. harzianum, A. niger and combination of both reduced
      the level of aflatoxin B(1) to a great extent. Leaf powder of W. somnifera, H.
      suaveolens, peel powder of C. sinensis, C. medica and pongamia cake also
      controlled the aflatoxin B(1) production. CONCLUSIONS: All the natural product
      treatments applied were significantly effective in inhibiting aflatoxin B(1)
      production on soybean seeds by A. flavus. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These natural plant products may successfully replace chemical fungicides and
      provide an alternative method to protect soybean and other agricultural
      commodities from aflatoxin B(1) production by A. flavus.

PMID- 17032219
TI  - Evaluation and applicability of a purification method coupled with nested PCR for
      the detection of Toxoplasma oocysts in water.
AB  - AIMS: To describe the development, evaluation and applicability of a complete
      method for the detection of Toxoplasma gondii in water. METHODS AND RESULTS: The
      method incorporated concentration of water samples by Al(2)(SO(4))(3)
      flocculation, purification by discontinuous sucrose gradients and detection of
      toxoplasmic DNA by 18S-rRNA nested PCR. Tap water replicates and natural water
      samples were seeded with defined numbers of Toxoplasma oocysts and processed for
      evaluation studies. When applied to environmental samples, the method gave
      highest detection sensitivities of 100 oocysts in river water and 10 oocysts in
      well- and sea water. The method was finally applied in 60 water samples of
      different quality and origin collected over a 14-month period. Toxoplasmic DNA
      was detected in four samples. CONCLUSIONS: The method offers an alternative
      towards improving current methods that can be used for the detection of
      Toxoplasma oocysts in environmental water samples. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The method in its current form will be helpful for assessment of
      Toxoplasma contamination in water resources, particularly after outbreak events.

PMID- 17032220
TI  - A preliminary assessment of Bacillus anthracis spore inactivation using an
      electrochemically activated solution (ECASOL).
AB  - AIM: To evaluate the efficacy of electrochemically activated solution (ECASOL) in
      decontaminating Bacillus anthracis Ames and Vollum 1B spores, with and without
      changing the source water hardness and final ECASOL pH. METHODS AND RESULTS: Five
      different ECASOL formulations were generated, in which the source water hardness
      and final ECASOL pH were varied, resulting in cases where significant changes in
      free available chlorine (FAC) and oxidative-reduction potential (ORP) were
      observed. B. anthracis Ames and Vollum 1B spores were suspended in the various
      ECASOL formulations for 30 min, and decontamination efficacy was determined;
      calcium hypochlorite [5% high-test hypochlorite (HTH)] was used as a positive
      control. The five different ECASOL formulations yielded mean FAC levels ranging
      from 305 to 464 ppm, and mean ORP levels ranging from +826 to +1000 mV. Exposure
      to all the ECASOL formulations and 5% HTH resulted in >or=7.0 log reductions in
      both B. anthracis Ames and Vollum 1B spores. CONCLUSIONS: The present testing
      demonstrated that ECASOL with a minimum of c. 300-ppm FAC levels and +800-mV ORP
      inactivated the B. anthracis spores in suspension, similar to 5% HTH.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information for
      decontaminating B. anthracis Ames and Vollum 1B spores in suspension using
      ECASOL.

PMID- 17032221
TI  - Subinhibitory concentrations of cinnamaldehyde interfere with quorum sensing.
AB  - AIMS: To investigate the effect of cinnamaldehyde (CA) on transcription from
      selected quorum sensing (QS) promoters. METHODS AND RESULTS: The action of CA on
      QS was assayed using three E. coli green fluorescent protein (GFP) based
      bioreporters (two inducible and the other constitutive) and two Vibrio harveyi
      bioluminescent reporter strains. LuxR-mediated transcription from the P(luxI)
      promoter, which is induced by 3-oxo-C6-homoserine lactone (HSL), was reduced by
      70 per cent following exposure to 200 micromol l(-1) CA (26 ppm). The
      bioluminescence of Vibrio harveyi BB886, which is mediated by 3-hydroxy-C4-HSL,
      was reduced by 55 per cent after exposure to 60 micromol l(-1) CA (8 ppm), and
      100 micromol l(-1) CA (13 ppm) inhibited the bioluminescence of the autoinducer-2
      (AI-2) responsive reporter strain V. harveyi BB170 by nearly 60 per cent. CA did
      not inhibit the growth of the bioreporter strains at these concentrations. CA had
      a minimal effect on LasR promoter activity, induced by 3-oxo-C12-HSL.
      CONCLUSIONS: Low concentrations of CA were effective at inhibiting two types of
      acyl homoserine lactone mediated QS, and also autoinducer-2 mediated QS.
      SIGNIFICANCE AND IMPACT OF STUDY: Because CA is widely used in the food and
      flavour industries, its potential to affect bacterial QS regulated processes
      should be recognized.

PMID- 17032222
TI  - Molecular identification of Bacillus thuringiensis var. israelensis to trace its
      fate after application as a biological insecticide in wetland ecosystems.
AB  - AIMS: To determine the fate of viable Bacillus thuringiensis var. israelensis
      (Bti) spores dispersed in the environment, using a universally applicable
      molecular detection methodology. METHODS AND RESULTS: Soil samples were spread on
      growth medium, after a temperature selection of the spores. A PCR amplification
      of the cry4Aa and cry4Ba insecticidal genes was applied on the colonies.
      Ribotyping was performed subsequently. This combined molecular method proved to
      be very specific for Bti, which was easily differentiated from the other B.
      thuringiensis serovars. A site regularly treated with Vectobac-G was chosen
      within the 'Bolle di Magadino' natural reserve, and monitored throughout 1 year
      for the detection of Bti spores. The results showed that the numbers were
      relatively high after insecticidal applications (1.4 x 10(5) CFU g(-1)), and
      decreased approx. 10-fold after 220 days. A successive treatment induced a new
      increase. CONCLUSIONS: The results show that yearly repeated use of Vectobac-G
      does not seem to have a major ecological impact on the 'Bolle di Magadino'
      natural reserve. Bti spores followed a trend leading to their eventual
      disappearance from the ecosystem, despite the seasonal application of this
      biological insecticide for more than a decade. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The molecular identification of Bti cells through the PCR analysis of the
      delta-endotoxins genes coupled to ribotyping, is an innovative method, that has
      enabled the identification of this organism into wetland environments.

PMID- 17032223
TI  - Inhibitory effects of Lactobacillus acidophilus lysates on the cytotoxic activity
      of shiga-like toxin 2 produced from Escherichia coli O157:H7.
AB  - AIMS: The purpose of this study was to characterize the degree to which four cell
      lysates obtained from Lactobacillus acidophilus strains affected the cytotoxic
      activity of Escherichia coli O157:H7 in vitro and in vivo. METHODS AND RESULTS:
      In a cytotoxic inhibition test that used 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and toxin-binding ELISA assays, the activity of shiga
      like toxin 2 (Stx-2) was inhibited profoundly by the cell lysates (10 mg ml(-1))
      from two strains of L. acidophilus A4 and 30SC (>85% of survival rates compared
      with the control) among the five strains tested. In particular, a significant
      decline in the virulence level of E. coli O157:H7, under the presence of the cell
      lysates of L. acidophilus A4, was observed by killing assay of Caenorhabditis
      elegans in vivo model. CONCLUSIONS: According to our results, L. acidophilus
      strains might be capable of attenuating the virulence of Stx-2 produced from E.
      coli O157:H7. SIGNIFICANCE AND IMPACT OF THE STUDY: The cell lysates of L.
      acidophilus can be applied to a variety of foods, and can be used as adjuncts for
      the inhibition of Stx-2-mediated cytotoxicity.

PMID- 17032224
TI  - In vitro growth inhibition of Helicobacter pylori by lactobacilli belonging to
      the Lactobacillus plantarum group.
AB  - AIMS: The aim of this study was to test and locate the in vitro anti-Helicobacter
      activity of seven Lactobacillus strains belonging to Lactobacillus plantarum
      group. METHODS AND RESULTS: Growth inhibition of H. pylori was tested using a
      well-plate assay. Of the strains displaying the strongest growth inhibition, a L.
      plantarum isolated from sauerkraut (MLBPL1) was chosen for further studies. The
      detected anti-Helicobacter activity of MLBPL1 was mainly associated with cell
      wall, and to a minor extent with the culture supernatant. The active component,
      which was determined to be between 3 and 10 kDa in size, retained its activity
      after 10 min treatment at 100 degrees C. The activity was present when MLBPL1 was
      cultivated in rich laboratory cultivation medium MRS and in different food
      matrices. CONCLUSIONS: The strains belonging to L. plantarum group showed anti
      Helicobacter activity in vitro. The main activity seemed to be associated with
      cell wall rather than culture supernatant or intracellular fraction. SIGNIFICANCE
      AND IMPACT OF THE STUDY: In view of the rapid spread of resistant H. pylori
      strains caused by antibiotic therapy, addition of a fermented food containing L.
      plantarum to the conventional antibiotic treatment of Helicobacter infection
      could establish a potential complementary means to suppress the infection.

PMID- 17032225
TI  - Simple conjugation and outgrowth procedures for tagging vibrios with GFP, and
      factors affecting the stable expression of the gfp tag.
AB  - AIM: Our goal was to develop a simple system for tagging wild-type marine
      bacteria with gfp. METHODS AND RESULTS: Escherichia coli strain CC118lambdapir
      carrying the conjugative helper plasmid pEVS104 and the gfp-containing plasmid
      pKV111 was used to transfer gfp to Vibrio recipients. Four different media were
      tested for their ability to support the growth of recipients, but not the E. coli
      donor, to allow powerful enrichment of gfp-tagged wild-type vibrios from mating
      mixes. Forty-three vibrio strains, representing 39 different species, were
      successfully tagged with gfp using the conjugative transfer from E. coli followed
      by selective outgrowth at 15 degrees C on ZoBell 2216E agar containing 0.5%
      sodium alginate. Using this outgrowth medium, colonies of GFP-expressing vibrio
      clones were detectable within 4 days. The percentage of visibly fluorescent cells
      in three representative GFP-tagged vibrios was higher at 15 degrees C than at 20
      or 25 degrees C (c. 50% vs. 45% or 40%, respectively), and was also higher during
      the aerobic rather than the anaerobic culturing (c. 50% vs. 35%, respectively).
      CONCLUSIONS: We found a simple selective outgrowth technique that enabled us to
      isolate a wide variety of GFP-tagged marine vibrios following the conjugative
      transfer of gfp from E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: Tagging cells
      with GFP and related fluorescent proteins is a powerful approach for
      investigating the bacteria in situ, particularly during the colonization of
      hosts. The simple and cost-effective outgrowth condition described in this study
      could be applied to construct a wide variety gfp-tagged marine bacteria.

PMID- 17032226
TI  - Effect of suspension media on nonthermal inactivation of Escherichia coli.
AB  - AIMS: To investigate the influence of suspension media on the survival of
      Escherichia coli M23 exposed to nonthermal, lethal stresses. METHODS AND RESULTS:
      Populations of E. coli M23 suspended in minimal medium (MM) or in different
      nutrient-rich broths were exposed to water activity 0.90 and/or pH 3.5 and
      inactivation was determined by culture-based enumeration. In response to the
      osmotic or acid challenges, E. coli M23 displayed enhanced survival in MM rather
      than in complex broth. That trend was reversed when populations were exposed to
      low water activity in combination with low pH. Comparison of microbial survival
      in three complex media indicated that even relatively small differences in
      composition influenced inactivation. In most media the combination of lethal
      stresses resulted in a synergism, which enhanced bacterial inactivation; however,
      an exception (tryptone soya broth) was observed. CONCLUSIONS: The suspension
      medium strongly influences the inactivation of E. coli M23 by osmotic and/or acid
      stresses. This should be considered when comparing studies of microbial survival
      that use different media and when broth-derived data are intended to represent
      specific environments (e.g. food matrices). SIGNIFICANCE AND IMPACT OF THE STUDY:
      The specific effects of synthetic media need to be appreciated when studying
      bacterial inactivation in conditions relevant to food-manufacturing regimes.

PMID- 17032227
TI  - Use of repetitive DNA sequences to determine the persistence of enteropathogenic
      Escherichia coli in vegetables and in soil grown in fields treated with
      contaminated irrigation water.
AB  - AIMS: Fresh fruits and vegetables are increasingly recognized as vectors for food
      borne illness. On farm contamination through contaminated irrigation water is
      considered likely source of the pathogen for several outbreaks. The purpose of
      this study is to investigate the possible similarity of strains of Escherichia
      coli isolated from the soil and vegetables irrigated by treated wastewater.
      METHODS AND RESULTS: Seventy-five strains of enteropathogenic Escherichia coli
      isolated from vegetables, soil and irrigation water were tested for sensitivity
      to antibiotics and shown to be sensitive. The result of enterobacterial
      repetitive intergenic consensus (ERIC)-PCR shows similarities between analysed
      strains isolated from the three different samples. Moreover strains of E. coli
      isolated from vegetables over different periods of time have the same ERIC-PCR
      profile. CONCLUSIONS: The isolated strains of enteropathogenic E. coli can
      persist in soil and in vegetables growing in fields treated with contaminated
      irrigation water for an extended period of time. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Contaminated irrigation water can transport pathogenic bacteria, which
      persists in the soil for a long period of time and contaminates the vegetables
      growing in the field irrigated by this contaminated water.

PMID- 17032228
TI  - Antibiotic resistance genes in multidrug-resistant Enterococcus spp. and
      Streptococcus spp. recovered from the indoor air of a large-scale swine-feeding
      operation.
AB  - AIMS: In this study, multidrug-resistant bacteria previously recovered from the
      indoor air of a large-scale swine-feeding operation were tested for the presence
      of five macrolide, lincosamide and streptogramin (MLS) resistance genes and five
      tetracycline (tet) resistance genes. METHODS AND RESULTS: Enterococcus spp. (n =
      16) and Streptococcus spp. (n =16) were analysed using DNA-DNA hybridization,
      polymerase chain reaction (PCR) and oligoprobing of PCR products. All isolates
      carried multiple MLS resistance genes, while 50% of the Enterococcus spp. and 44%
      of the Streptococcus spp. also carried multiple tet resistance genes. All
      Enterococcus spp. carried erm(A) and erm(B), 69% carried erm(F), 44% carried
      mef(A), 75% carried tet(M), 69% carried tet(L) and 19% carried tet(K). All
      Streptococcus spp. carried erm(B), 94% carried erm(F), 75% carried erm(A), 38%
      carried mef(A), 50% carried tet(M), 81% carried tet(L) and 13% carried tet(K).
      CONCLUSIONS: Multidrug resistance among airborne bacteria recovered from a swine
      operation is encoded by multiple MLS and tet resistance genes. These are the
      first data regarding resistance gene carriage among airborne bacteria from swine
      feeding operations. SIGNIFICANCE AND IMPACT OF THE STUDY: The high prevalence of
      multiple resistance genes reported here suggests that airborne Gram-positive
      bacteria from swine operations may be important contributors to environmental
      reservoirs of resistance genes.

PMID- 17032229
TI  - Evaluation of antimicrobial activity in Paenibacillus spp. strains isolated from
      natural environment.
AB  - AIMS: Paenibacillus isolates were selected to test antimicrobial activity against
      bacteria, filamentous fungi and yeasts isolates, with the purpose of finding new
      bacterium species for microbiological control. METHODS AND RESULTS: Fifty-five
      strains belonging to 15 species of Paenibacillus were inoculated on trypticase
      soya agar, potato dextrose agar and sabouraud agar plates in order to evaluate
      their antimicrobial activity against 16 indicator bacteria, 14 filamentous fungi
      and six yeasts isolates, both reference and field strains. After these screening,
      culture supernatant of 17 isolates was prepared. Twenty-five Paenibacillus
      isolates presented antimicrobial activity, where seven species (Paenibacillus
      chibensis; P. koreensis; P. illinoiensis; P. validu; P. pabuli; P. brasilensis
      and P. peoriae) stood out inhibiting at least 13 of the 16 indicator bacteria.
      Only 14 of the 55 isolates exhibited antifungal activity. P. peoriae inhibited 13
      among the 14 filamentous fungi and all yeasts indicator strains. Fourteen
      isolates produced culture supernatant with antimicrobial activity. CONCLUSIONS:
      Among the 55 isolates analysed, 25 exhibited a broad inhibition spectrum against
      bacteria and pathogenic fungi. P. validus, P. chibensis, P. koreensis and P.
      peoriae isolates proved to be the subject matter for studies on the production of
      antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study
      revealed other two species with antimicrobial activity: P. validus and P.
      chibensis, and it contributed to enhance Paenibacillus biocontrolling potential,
      proving that it exhibit a broad action spectrum.

PMID- 17032230
TI  - Optimization of culture conditions for production of antimalarial menisporopsin A
      by the seed fungus Menisporopsis theobromae BCC 4162.
AB  - AIMS: The aim of this work was to optimize the production of a novel antimaralial
      menisporopsin A by the seed fungus Menisporopsis theobromae BCC 4162. METHODS AND
      RESULTS: Fungal cultures were grown in shake flasks at 25 degrees C in the basal
      medium with varying carbon and nitrogen sources, aeration rates and initial pH
      levels. The optimal carbon and nitrogen sources that improved the production of
      menisporopsin A were 1% fructose and 2.5% meat extract respectively. The
      production was further enhanced when the culture incubated on a shaker at 200 rev
      min(-1) with an initial pH of 8. The yield of menisporopsin A cultured under the
      optimized conditions was increased from 348.30 (obtained from basal medium) to
      889.02 mg l(-1), and the cultivation time was reduced from 28 to only 4 days. As
      a result, the productivity of menisporopsin A was greatly enhanced to 222.26 mg
      l(-1) day(-1) which is 18-fold higher than that of basal conditions. Larger scale
      production in a fermenter was also achieved, yielding menisporopsin A at a
      maximal level of 594.32 mg l(-1) in 4 days. CONCLUSIONS: The optimized culture
      conditions for menisporopsin A production by M. theobromae BCC 4162 was the
      cultivation under shaking or agitation at 25 degrees C in fructose-meat extract
      medium with an initial pH of 8. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      production of menisporopsin A in a fermenter with a relatively short incubation
      period could be valuable for further utilization for chemical structure
      modification and derivatization.

PMID- 17032231
TI  - Prevalence and lineages of Listeria monocytogenes in Chinese food products.
AB  - AIMS: This study was undertaken to investigate the prevalence and lineages of
      Listeria monocytogenes in different kinds of food products in local Chinese
      markets. METHODS AND RESULTS: A total of 2686 food samples and 645 water samples
      were collected and L. monocytogenes was isolated from 2.28% (76 of 3331) of all
      samples. The prevalence of L. monocytogenes (14 of 290, 4.83%) in raw meat
      products was significantly higher than that in other raw food products (P <
      0.05). Among 844 ready-to-eat (RTE) food samples, 21 samples were positive for L.
      monocytogenes. RTE packaged food products from two supermarkets had a prevalence
      ranging from 0.00% to 25.00%. The prevalence of L. monocytogenes in meat products
      of freshly slaughtered hogs was 0.95% (four of 420), significantly lower than
      that in raw meat products in the retail markets (P < 0.05). Ten isolates were
      recovered from 645 water samples, which were collected after hands washing by
      shopkeepers or waiters. A total of 38 isolates were randomly selected for lineage
      classification based on the nucleotide variation of actA gene. Eighty percentage
      of isolates from RTE food products belonged to Lineage II while only 20% belonged
      to Lineage I. CONCLUSIONS: Food products in Chinese markets are contaminated with
      L. monocytogenes. Raw meat products have the highest contamination rates among
      all the raw food samples. RTE food products are more likely to be contaminated
      with Lineage II strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The data presented
      here show the main contamination sources of L. monocytogenes in Chinese food
      products.

PMID- 17032232
TI  - Antimicrobial resistance profiling and fla-typing of Irish thermophillic
      Campylobacter spp. of human and poultry origin.
AB  - AIMS: To determine the genetic relationship between a random collection of Irish
      human and poultry Campylobacter isolates and to determine the frequency of
      antibiotic resistance. METHODS AND RESULTS: Sixty-six Campylobacter isolates (34
      human and 32 poultry) were typed by restriction fragment length polymorphism of
      flagellin-A (flaA) PCR products (flaA-RFLP) and by sequencing of the short
      variable region of flaA (flaA-SVR). FlaA-RFLP identified 58 distinct profiles,
      while flaA-SVR identified 28 different alleles. The highest level of antibiotic
      resistance was found for ampicillin (48.5%) followed by nalidixic acid (42.2%)
      and ciprofloxacin (31.8%). In general, poultry isolates displayed a higher
      incidence of resistance to the antimicrobials tested than the human isolates.
      CONCLUSIONS: A high level of genetic diversity existed among the Campylobacter
      strains confirming the weak clonality of this species. There was no relationship
      between antimicrobial resistance and specific genotypes determined by flaA typing
      suggesting that resistance was due to pressures of antimicrobial therapy.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study emphasizes the need for
      increased surveillance of antimicrobial susceptibility among Campylobacter
      isolates in Ireland and the implementation of more stringent control policies
      relating to the use of antimicrobials in the poultry industry.

PMID- 17032233
TI  - Phenotypic and molecular typing of Vibrio harveyi isolates and their
      pathogenicity to tiger shrimp larvae.
AB  - AIMS: The objective of the present study was to identify the biotype(s) and
      molecular type(s) of Vibrio harveyi associated with pathogenicity in tiger shrimp
      (Penaeus monodon) larvae. METHODS AND RESULTS: Five luminescent and four
      nonluminescent V. harveyi isolates were subjected to phenotyping and random
      amplified polymorphic DNA (RAPD) fingerprinting, and pathogenicity testing to P.
      monodon mysis. Four isolates induced 34-41% mortality of P. monodon mysis when
      challenged at the rate of 10(6) CFU ml(-1) within 60 h. Sucrose-fermenting
      biotypes of V. harveyi appeared to be associated with pathogenicity to larval
      shrimp. Higher temperature and salinity appeared to play a role on the onset of
      vibriosis and mortality in the challenged larval shrimp. Pathogenic isolates of
      V. harveyi could be demarcated as revealed by their clustering in the dendrogram
      constructed based on the RAPD fingerprints. CONCLUSIONS: Nonluminescent V.
      harveyi also appear to be important aetiological agents of vibriosis of shrimp
      larvae. Sucrose-fermenting biotypes are likely to be pathogenic. High temperature
      may trigger onset of vibriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Biotyping
      of V. harveyi isolates and looking for traits, such as ability to ferment sucrose
      may be helpful in identifying the pathogenic forms, and such approach requires to
      be investigated further with larger number of isolates.

PMID- 17032234
TI  - Isolation and characterization of exopolysaccharide produced by Vibrio harveyi
      strain VB23.
AB  - AIMS: The aim of the study was to isolate and characterize exopolysaccharide
      (EPS) produced by Vibrio harveyi strain VB23. METHODS AND RESULTS: Growth and EPS
      production by V. harveyi strain VB23, was studied in mineral salts medium
      supplemented with NaCl (1.5%) and glucose (0.2%). The rate of EPS production in
      batch cultures was highest during the late log phase of growth when compared with
      stationary growth phase. The exopolymer was recovered from the culture
      supernatant by using a cold ethanol precipitation-dialysis procedure. Chemical
      analyses of EPS revealed that it is primarily composed of neutral sugars, uronic
      acids, proteins and sulfates. The purified EPS revealed prominent functional
      reactive groups, such as hydroxyl, carboxylic and amides, which correspond to a
      typical heteropolymeric polysaccharide and the EPS, also possessed good
      emulsification activity. The gas chromatographic analysis of an alditol acetate
      derivatized sample of EPS revealed that it is composed primarily of galactose and
      glucose. Minor components found were rhamnose, fucose, ribose, arabinose, xylose
      and mannose. CONCLUSIONS: The EPS produced by V. harveyi strain VB23 is a
      heteropolysaccharide possessing good emulsification activity. EPS was readily
      isolated from culture supernatants, which suggests that the EPS was a slime-like
      EPS. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of EPS
      characterization in luminous V. harveyi bacteria, which describes the isolation
      and characterization of an EPS expressed by V. harveyi. The results of the study
      contributes significantly towards an understanding of the chemical composition
      and applications of the EPS in environmental biotechnology and bioremediation.

PMID- 17032235
TI  - Detection of Lactobacillus gasseri OLL2716 strain administered with yogurt drink
      in gastric mucus layer in humans.
AB  - In animal models and human trials, Lactobacillus gasseri OLL2716 (LG21) strain
      suppressed Helicobacter pylori colonization in the stomach. The aim of the
      present study was to clarify whether orally administered LG21 strain can enter
      the gastric mucus layer. Biopsy samples were taken from the gastric antrum and
      corpus of two healthy volunteers (H. pylori infected and non-infected) who drank
      yogurt supplemented with LG21 strains. DNA of LG21 and H. pylori in the mucus
      layer was detected using the laser-assisted microdissection and non-contact
      pressure catapulting (LMPC) method and the semi-nested PCR method with primer
      sets of RNA helicases of superfamily II gene-Insertion sequence for LG21 strain
      and those of ureA gene for H. pylori. In the volunteer with H. pylori infection,
      DNA fragments of LG21- and H. pylori-specific regions from both antrum and corpus
      were amplified, whereas in a non-infected volunteer, only the LG21 DNA from the
      antrum was amplified. The present study demonstrated that LG21 strains
      administered through a yogurt drink can enter into the gastric mucus layer. Our
      novel method may be useful in studying gastric probiotics for H. pylori
      infection.

PMID- 17032237
TI  - Influence of high-fat feeding on both naive and antigen-experienced T-cell immune
      response in DO10.11 mice.
AB  - Obesity is becoming one of the most serious public health problems in
      industrialized societies, due to the profound changes in lifestyle, and notably
      in nutrition. Beside diabetes, cardiovascular diseases or hypertension, increased
      susceptibility to infection is one of the pathological consequences of being
      overweight. In this paper, we have assessed the influence of a high-fat diet
      (HFD) rich in saturated fatty acids on the immune system of DO11.10 mice, which
      are transgenic for a T-cell receptor specifically recognizing a peptide of
      ovalbumin. We showed that the specific T-cell immune response was impaired by
      high-fat feeding, and that the expression of this defect is different depending
      on whether T cells are naive or Ag experienced. Indeed, on in vitro ovalbumin
      stimulation, spleen T cells from naive HFD-fed transgenic mice showed
      proliferation similar to that of cells from standard diet (SD)-fed mice, but
      exhibited a strong inflammatory profile as shown by the markedly increased IFN
      gamma/IL-4 ratio. Inversely, spleen T cells from ovalbumin-immunized HFD mice
      were impaired in their Ag-dependent proliferation compared to cells from SD mice.
      By co-culture experiments, we showed that both T cells and antigen-presenting
      cells were involved in this impairment. Moreover, in ovalbumin-immunized HFD
      animals, a trend towards Th2 response was noted, compared to immunized SD mice.
      This data implies that naive T cells could participate actively in the low-grade
      systemic inflammation observed in overweight patients. Moreover, the impaired
      activity of Ag-experienced T cells could have major consequences both in defence
      against infection and/or in vaccination protocols.

PMID- 17032238
TI  - Impact of influenza vaccine formulation with a detailed analysis of the cytokine
      response.
AB  - Vaccination provides the most effective method of limiting the impact of
      influenza. Inactivated influenza vaccines are available in three formulations and
      more information needs to be generated on how antigen presented in different
      vaccine formulations influences the subsequent immune response. In the present
      study, we have investigated the effect of two different influenza vaccine
      formulations on the resulting antibody and cytokine responses and compared these
      responses with influenza infection. Mice were vaccinated intramuscularly with one
      or two doses of whole or split virus vaccine or alternatively intranasally
      infected with influenza virus. Lymphocytes were isolated from spleen cells and
      stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene
      expression and at the protein level. Additionally, whole blood was collected and
      the serum antibody response investigated by haemagglutination inhibition (HI) and
      enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus
      vaccine induced higher antibody and cytokine responses and thus was more
      immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine
      induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and
      a more mixed cytokine response after the second dose. Split virus vaccine induced
      a type 2 response, particularly after two vaccine doses. Our results show that
      two doses of vaccine (both vaccine formulation) were more effective in induction
      of Th2 type of cytokines and thus indicate that both the formulation and also the
      number of vaccine doses substantially influences the magnitude and quality of the
      immune response.

PMID- 17032239
TI  - Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B
      and ESAT-6 antigens of Mycobacterium tuberculosis.
AB  - Antigen 85B (Ag85B) and ESAT-6 are important immunodominant antigens of
      Mycobacterium tuberculosis, and both are very promising vaccine candidate
      molecules. In this study, we relied on the T-cell epitopes of Ag85B and ESAT-6 to
      design a chimaeric protein by inserting ESAT-6 into Ag85B from the amino acids
      167-182. We found the ratio of IgG2b/IgG1 and the secretion of interferon (IFN)
      gamma in the mice vaccinated with the new protein with adjuvant MPL and TDM were
      higher than the mice immunized with fusion protein Ag85B-ESAT-6, which have been
      reported and could induce levels of protective immunity similar to BCG in the
      mouse model of tuberculosis (TB) infection. These results suggest that the
      chimaeric protein Ag85B(N)-ESAT-6-Ag85B(C) is a strong candidate for further
      study and the T-cell epitopes of the antigens should be considered when we design
      the subunit vaccine.

PMID- 17032240
TI  - B-cell CD25 expression in murine primary and secondary lymphoid tissue.
AB  - B cells are in analogy with T cells capable of expressing functional IL-2
      receptors. IL-2R alpha-chain (CD25) positive T cells have been studied in detail
      but not much is known about CD25 positive B cells. The aim of this study was to
      examine the phenotypic properties of the CD25 expressing B cells collected from
      different lymphoid organs in mice. Samples were stained for various cell surface
      markers and analysed using flow cytometry. We found that approximately 49% of B
      cells in bone marrow, 16% in peritoneal cavity, 2% in spleen and 1% in lymph
      nodes express CD25. In contrast, CD25 expressing B cells were not found in the
      blood or in Peyer's patches. Phenotypic characterization showed that CD25+ B
      cells in spleen, lymph nodes and peritoneal cavity have higher expression of
      AA4.1, CD5, CD69, CD80, CD86, CD122, CD132, IgA, IgG and IgM on their surface in
      comparison with CD25- B cells. In contrast, expression of IgD and IA-IE was lower
      on CD25+ B cells in spleen and lymph nodes. In bone marrow, the expression of
      CD5, CD80, CD86, CD122, CD132, IgA, IgD and IgM was lower, while the expression
      of AA4.1, IgG and IA-IE was increased on CD25+ B cells compared with CD25- B
      cells. In conclusion, our results indicate that B cells expressing CD25 are
      phenotypically distinctly different from those that are CD25 negative. Our
      findings suggest that CD25+ B cells are more prone to efficient antigen
      presentation and display a more mature phenotype.

PMID- 17032241
TI  - Dendritic cells therapy confers a protective microenvironment in murine
      pregnancy.
AB  - The fetal-placental unit is a semi-allograft and immunological recognition of
      pregnancy, together with the subsequent response of the maternal immune system,
      is necessary for a successful pregnancy. Dendritic cells (DC) show a biological
      plasticity that confers them special characteristics regulating both immunity and
      tolerance. Therapy employing DC proved to diminish the abortion in the DBA/2J
      mated CBA/J females; however, the underlying mechanisms remain unknown. Here, we
      evaluated whether DC therapy influences the presence of immunoregulatory
      populations of cells at the fetal-maternal interface. To address this hypothesis,
      we analysed the pregnancy-protective CD8, gammadelta cell populations as well as
      transforming growth factor (TGF)-beta1 and progesterone-induced blocking factor
      (PIBF) expression at the fetal-maternal interface from abortion-prone female mice
      that had previously received adoptive transfer of syngeneic DC. Syngeneic DC
      therapy induced an increase in the number of CD8 and gammadelta cells.
      Additionally, an upregulation of TGF-beta1 and PIBF expression could be detected
      after DC transfer. We suggest that DC therapy differentially upregulates a
      regulatory/protective population of cells at the fetal-maternal interface. It is
      reasonable to assure that this mechanism would be responsible for the lower
      abortion rate.

PMID- 17032242
TI  - Regulatory activity of activated murine peripheral CD4+CD25- T cells: a possible
      mechanism of feedback regulation on adaptive immunity.
AB  - This study was undertaken to investigate the possibility that peripheral CD4+CD25
      T cells, once fully activated, transiently obtain suppressive function against
      other T cells. CD4+CD25- T cells, isolated from splenocytes of BALB/c mice, were
      stimulated with anti-CD3 MoAb in the presence of feeder cells for 72 h. The
      activated CD4+ T cells (T(act)) thus obtained were able to inhibit the activation
      and proliferation of bystander CD4+ T cells in a non-MHC-restricted manner.
      T(act)-mediated suppression was cell contact dependent, reversible by exogenous
      IL-2 as well as anti-GITR antibody. Furthermore, adoptive transfer of T(act)
      cells significantly downregulated humoral response of BALB/c mice to s.c.
      immunization with ovalbumin. We argue that suppression mediated by activated
      CD4+CD25- T cells may play an important role in maintaining homeostasis of the
      immune system and preventing excessive T-cell responses in vivo.

PMID- 17032243
TI  - Measurement and significance of 3-nitrotyrosine in systemic lupus erythematosus.
AB  - Nitration of free and protein associated tyrosine represents, in vivo, a
      mechanism that can severely compromise the cell function. The detection of 3
      nitrotyrosine (3-NT) in pathological tissues is suggestive of the occurrence of
      nitrating pathways and has been identified as a marker of inflammation and a
      stable end product of increased reactive nitrogen intermediate production.
      Protein nitration occurs in many disease conditions including systemic lupus
      erythematosus (SLE). In this study we show that the level of both free and
      protein bound 3-NT, which is produced by reactive nitrogen species (RNS)
      dependent oxidative damage, is elevated in patients with SLE and that there is a
      possible role of RNS-modified epitopes in the aetiology of the disease.
      Commercially available poly L-tyrosine was exposed to nitrating species, inducing
      nitration in tyrosine residues. Immunoglobulin-G (IgG) purified on Protein-A
      Sepharose matrix from 24 SLE patients was studied for their recognition of native
      and nitrated poly L-tyrosine by direct binding and competition enzyme-linked
      immunosorbent assay (ELISA). The formation of immune complex between SLE IgG and
      nitrated poly L-tyrosine was visualized by gel retardation assay. Free 3-NT in
      patients' sera was detected and quantitated by high performance liquid
      chromatography whereas protein-bound 3-NT was analysed by Western blotting and
      the concentration was calculated by sandwich ELISA. The concentration of free 3
      NT was found to be 1.4 +/- 0.09 microm whereas the concentration of protein bound
      3-NT was 96.52 +/- 21.12 microm nitrated bovine serum albumin equivalents/mg
      protein, which was significantly higher when compared with healthy controls.
      Elevated level of 3-NT was observed in SLE patients using two different
      techniques, when compared with healthy subjects confirms the overproduction of
      RNS in the pathogenesis of human SLE.

PMID- 17032244
TI  - Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion
      in rheumatoid arthritis.
AB  - Interleukin (IL)-21 is a CD4+ T-cell-derived cytokine, which is involved in
      innate and adaptive immune response. In this study, we analysed IL-21 receptor
      (IL-21R) expression in peripheral blood and synovial fluid mononuclear cells, and
      investigated the role of IL-21 in the induction of proinflammatory cytokine
      production by peripheral blood T cells (PB-T) and synovial fluid T cells (SF-T)
      from patients with rheumatoid arthritis (RA). Immunohistochemical staining
      demonstrated that IL-21R-positive cells were significantly increased in inflamed
      synovial tissues of RA patients compared with osteoarthritis (OA) and healthy
      controls. Flow cytometric analysis confirmed that IL-21R was mainly expressed in
      freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial
      fluid, but decreased gradually in T cells 24 h after anti-CD3 stimulation. PB-
      and SF-T cells from RA patients were more responsive to IL-21 when compared with
      controls. Importantly, isolated PB- or SF-T cells from RA patients, when
      stimulated with IL-21 and anti-CD3 MoAb, secreted markedly higher levels of TNF
      alpha and IFN-gamma than controls. These data indicate that IL-21R is
      overexpressed in the inflamed synovial membrane and in peripheral blood or
      synovial fluid leukocytes of RA patients, and that IL-21 enhances local T-cell
      activation, proliferation and proinflammatory cytokine secretion. Thus, blockade
      of IL-21R signalling pathway may have a therapeutic potential in acute RA
      patients.

PMID- 17032245
TI  - Dysregulation of TNF/TNFR superfamily members: a systemic link between intra- and
      extrathyroidal manifestations in Graves' disease.
AB  - Graves' disease (GD) coincides with the occurrence of disease-associated
      intrathyroidal dendritic cells (DC) and intraorbital inflammatory macrophages
      (Mphi). Physiologically, tumour necrosis factor-alpha (TNF-alpha) strongly
      affects the differentiation of DC and Mphi from monocytic precursors; we thus
      hypothesized that dysregulation of the TNF/TNFR superfamilies may provide a
      systemic pathogenic link in GD. In patients without eye symptoms, percentages of
      TNF-alpha-stimulated blood monocytes were highly significantly (P < 0.001)
      elevated, corresponding to both intrathyroidal DC maturation as well as increases
      in mature blood DC (MHC-II(hi)/CD40+/RFD1(hi)) and B cells (CD20(hi)/CD40+). GD
      patients also displaying eye symptoms revealed a striking reduction in blood
      monocytes, yet significantly (P < 0.05) increased CD40(hi) and TNF-alpha(hi)
      leucocytes. These findings suggest for GD that excess TNF-alpha induces monocytes
      to differentiate into hyperactivated thyroidal DC that, once emigrated, initiate
      systemic humoral autoimmunity associated with CD40/TNF-alpha upregulation. Such
      overexpression may instigate differentiation of periorbital inflammatory Mphi
      from CD14(hi)/CD16+ monocytes as a likely precursor subset. These results
      indicate that dysregulation of TNF/TNFR superfamily members provides a systemic
      pathogenic link in GD in that hyperactivated circulating monocytic precursors
      give rise to locally restricted, disease-associated DC and Mphi. Monocytes,
      therefore, may serve as a suitable target to therapeutically address the common
      precursor of key promoters of GD.

PMID- 17032246
TI  - Immune regulatory T cells in siblings of children suffering from type 1 diabetes
      mellitus.
AB  - Patients with type 1 diabetes are suffering from defects in immune regulatory
      cells. Their siblings may be at increased risk of type 1 diabetes especially if
      they are carriers of certain human leucocyte antigen (HLA) alleles. In a
      prospective non-randomized study, we intended to evaluate 31 healthy siblings of
      paediatric patients with type 1 diabetes and explore immune regulatory
      populations of CD4+CD25+ T cells and natural killer (NK) T cells. Tested siblings
      of type 1 diabetes patients were stratified according to the HLA-associated risk
      of possible diabetes development. Immune regulatory function of CD4+CD25+ T cells
      was tested in vitro. Significant differences in CD4+CD25+ but not in NK T cells
      have been identified. Siblings of type 1 diabetes patients carrying high risk HLA
      alleles (DQA1*05, DQB1*0201, DQB1*0302) had significantly lower number of immune
      regulatory CD4+CD25+ T cells than the age-matched healthy controls or siblings
      carrying low-risk HLA alleles (DQB1*0301, DQB1*0603, DQB1*0602). Regulatory
      function of CD4+CD25+ T cells demonstrated a dose-escalation effect. In siblings
      of type 1 diabetes patients, the defect in immune regulatory CD4+CD25+ T cells
      exists in association with genetic HLA-linked risk for type 1 diabetes.

PMID- 17032247
TI  - Frequency analysis of HBsAg-specific B lymphocytes in high-responder individuals
      to recombinant hepatitis B vaccine: comparison of LDA and ELISPOT assays.
AB  - The determination of the frequency of antigen-specific lymphocytes may provide
      invaluable information for the evaluation of the immune response to different
      antigens and pathogens. Different methods are employed to determine the frequency
      of specific B lymphocytes in peripheral blood. In this study, the frequency of
      hepatitis B surface antigen (HBsAg)-specific B lymphocytes was determined by a
      limiting dilution assay (LDA) and an enzyme-linked immunospot assay (ELISPOT) in
      seven healthy adult high responders to recombinant HBsAg. Peripheral blood
      mononuclear cells isolated at different time intervals (1, 2, 4, 8 and 16 weeks)
      following administration of a booster dose were either transformed with Epstein
      Barr virus (LDA) or stimulated with Pokeweed mitogen (ELISPOT). In an LDA, anti
      HBs positive wells were screened by a sandwich ELISA and the frequency of
      specific B lymphocytes was estimated based on the Poisson statistical analysis.
      In an ELISPOT, coloured spots representing specific B lymphocytes were finally
      enumerated by stereomicroscope. Our results showed a significant increase in the
      number of specific B lymphocytes in the first week by an ELISPOT compared with an
      LDA (1:190 versus 1:13,462) (P < 0.001). No significant differences were observed
      at other time intervals. A significant correlation was observed between the serum
      titer of anti-HBs antibody and frequency of HBsAg-specific B cells obtained by
      LDA and ELISPOT methods at different time intervals. The highest correlation was
      found at fourth week in LDA (r = 0.83, P < 0.01) and ELISPOT (r = 0.85, P < 0.01)
      assays. Furthermore, a significant correlation was observed between an LDA and
      ELISPOT at different time intervals (highest correlation in second week, r =
      0.88, P < 0.008). These findings suggest that in addition to technical
      advantages, such as speed and simplicity, an ELISPOT is a more sensitive assay,
      compared with an LDA.

PMID- 17032248
TI  - Anti-TNF effects on destructive fibroblasts depend on mechanical stress.
AB  - Joint destruction in rheumatoid arthritis (RA) starts typically at sites of
      mechanically stressed inserts of the synovial membrane near the cartilage/bone
      border. In the therapy of RA, tumour necrosis factor (TNF) antagonists have
      rapidly emerged as a valuable class of anti-rheumatic agents that reduce joint
      destruction. The aim of this study was to investigate and profile genes involved
      in the interaction between articular movement and anti-TNF therapy in an in vitro
      model. Murine LS48 cells, an established substitute for invasive RA synovial
      fibroblasts, were cultured, stretched and/or treated with anti-TNF-alpha antibody
      for 24 h. RNA was isolated and gene transcript levels were determined using
      U74Av2 Affymetrix GeneChips to identify transcriptional events. Positive findings
      were verified by polymerase chain reaction (PCR). We identified 170
      differentially regulated genes, including 44 of particular interest. Gene
      expression fell into different functional groups that can be explained by RA
      pathogenesis and experimental conditions. For 21 genes of the 44 of particular
      interest, regulation could be confirmed by real-time PCR. Remarkably, we found
      structural as well as functional genes differently regulated between stretched
      cells, anti-TNF-treated cells, and stretched cells treated with anti-TNF
      antibody. Additionally, we also found a large number of genes that are apparently
      not related to the experimental conditions. Mechanical exertion modulates gene
      expression and subsequently cellular response to anti-TNF therapy. Results in
      exerted cells correspond to current knowledge regarding RA pathogenesis and
      underline the relevance of our experimental approach. Finally, the central
      function of the interleukin-18 system in joint destruction could be confirmed by
      our findings.

PMID- 17032249
TI  - Benznidazole treatment during early-indeterminate Chagas' disease shifted the
      cytokine expression by innate and adaptive immunity cells toward a type 1
      modulated immune profile.
AB  - Trypanosoma cruzi-infected children was treated with benznidazole (Bz) during the
      early-indeterminate disease (E-IND) and the cytokine pattern of innate and
      adaptive immune compartments were evaluated prior to the treatment and 1 year
      after it. At first, we observed that the ex vivo cytokine profile of circulating
      leukocytes from E-IND (n = 6) resembled the one observed for healthy
      schoolchildren (n = 7). Additionally, in vitro stimulation with T. cruzi antigens
      drove the E-IND cytokine pattern toward a mixed immune profile with higher levels
      of IFN-gamma+, TNF-alpha+ and IL-4+ NK cells, increased numbers of IFN-gamma+,
      TNF-alpha+ and IL-10+ CD4+ T cells in addition to enhanced frequency of TNF
      alpha+/IL-4+ CD19+ lymphocytes. Interestingly, upon T. cruzi antigen in vitro
      stimulation, E-IND CD8+ lymphocytes displayed a selective enhancement of IFN
      gamma expression, accounting for a global type 1-modulated cytokine
      microenvironment. A shift toward a type 1-modulated profile was also the hallmark
      of Bz-treated children (E-IND(T)). In this context, despite the mixed overall ex
      vivo cytokine profile observed for NK and CD8+ T cells, increased ability of
      these leukocytes to produce IFN-gamma in response to T. cruzi antigens was
      reported. Most noteworthy was the IL-10 production evidenced at T lymphocytes,
      mainly CD4+ cells, as well as B lymphocytes, both ex vivo and upon antigen
      stimulation. Together, these findings gave evidence that NK cells and CD8+ T
      lymphocytes are the major sources of IFN-gamma, a pivotal cytokine for successful
      therapeutic response in human Chagas' disease. Moreover, our data have also
      brought additional information, pointing out IL-10 production by CD4+ cells and B
      lymphocytes, as the putative key element for parasite clearance in the absence of
      deleterious tissue damage.

PMID- 17032250
TI  - Preparation, characterization and epitope mapping of monoclonal antibodies
      specific to human mast cell carboxypeptidase.
AB  - Human mast cell carboxypeptidase (hMC-CP) is a unique product of mast cells.
      Unlike tryptase and chymase, its potential function and expression in diseased
      conditions remain largely unknown. To develop an assay for hMC-CP, the
      recombinant fusion protein of hMC-CP and purified native skin hMC-CP was
      prepared, and two novel monoclonal antibodies against hMC-CP named CCP1 (IgG1
      isotype) and CCP2 (IgM isotype) were raised in the present study. Epitope
      analysis shows that CCP1 and CCP2 antibodies recognize epitopes located in the
      region of amino acids 112-202 of hMC-CP, and hydrophilicity analysis implies that
      epitopes might be located in the amino acid residues 123-134 and 165-177.
      Furthermore, using a competition enzyme-linked immunosorbent assay, it was shown
      that the epitope recognized by CCP1 is close to that recognized by CCP2 or the
      two antibodies partially share the same epitope. Flow cytometry analysis shows
      that basophilic leukemia cell line KU812 reacts with both CCP1 and CCP2
      antibodies, suggesting that this cell line expresses hMC-CP. In conclusion,
      although the two antibodies possess different isotypes, they may partially share
      the same epitope. These two antibodies will be valuable tools for the development
      of an assay to detect the levels of hMC-CP in the biological fluids in man.

PMID- 17032251
TI  - Modulation of chemokine gene expression in CD133+ cord blood-derived human mast
      cells by cyclosporin A and dexamethasone.
AB  - We have recently developed a protocol for generating huge numbers of mature and
      functional mast cells from in vitro differentiated umbilical cord blood cells.
      Using CD133 as a positive selection marker to isolate haematopoietic progenitors
      we routinely expand the number of recovered cells at least 150-fold, which vastly
      exceeds the yields of conventional protocols using CD34+ cells as a source of
      progenitors. Taking advantage of the large quantities of in vitro differentiated
      mast cells, here we assess at the levels of transcription and translation the
      kinetics of chemokine gene induction following receptor mediated mast cell
      activation or following pharmacological activation of specific signal
      transduction cascades that become activated upon classical FcepsilonRI receptor
      crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP
      1alpha, and MIP-1beta are induced with different kinetics and with different
      amplitudes in a receptor activation dependent manner, and that these events can
      be mimicked using pharmacological agents which activate distinct signal
      transduction pathways. These findings were corroborated by adding
      immunomodulators such as cyclosporin A and dexamethasone prior to mast cell
      activation. Finally, we demonstrate that the same modulators added after mast
      cell activation can differentially quench ongoing chemokine gene induction. Thus,
      considering the vast yields of mast cells, our protocol is valuable not only for
      studying regulation of gene expression in mast cells in general, but also as an
      experimental tool to develop better and more balanced treatments of mast cell
      related disorders.

PMID- 17032252
TI  - Phytochrome-mediated development in land plants: red light sensing evolves to
      meet the challenges of changing light environments.
AB  - Phytochromes are photoreceptors that provide plants with circadian, seasonal, and
      positional information critical for the control of germination, seedling
      development, shade avoidance, reproduction, dormancy, and sleep movements.
      Phytochromes are unique among photoreceptors in their capacity to interconvert
      between a red-absorbing form (absorption maximum of approximately 660 nm) and a
      far-red absorbing form (absorption maximum of approximately 730 nm), which occur
      in a dynamic equilibrium within plant cells, corresponding to the proportions of
      red and far-red energy in ambient light. Because pigments in stems and leaves
      absorb wavelengths below about 700 nm, this provides plants with an elegant
      system for detecting their position relative to other plants, with which the
      plants compete for light. Certain aspects of phytochrome-mediated development
      outside of flowering plants are strikingly similar to those that have been
      characterized in Arabidopsis thaliana and other angiosperms. However, early
      diverging land plants have fewer distinct phytochrome gene lineages, suggesting
      that both diversification and subfunctionalization have been important in the
      evolution of the phytochrome gene family. There is evidence that
      subfunctionalization proceeded by the partitioning among paralogues of
      photosensory specificity, physiological response modes, and light-regulated gene
      expression and protein stability. Parallel events of duplication and functional
      divergence may have coincided with the evolution of canopy shade and the
      increasing complexity of the light environment. Within angiosperms, patterns of
      functional divergence are clade-specific and the roles of phytochromes in A.
      thaliana change across environments, attesting to the evolutionary flexibility
      and contemporaneous plasticity of phytochrome signalling in the control of
      development.

PMID- 17032253
TI  - Blind population genetics survey of tropical rainforest trees.
AB  - Rainforest tree species can be difficult to identify outside of their period of
      reproduction. Vascular tissues from Carapa spp. individuals were collected during
      a short field trip in French Guiana and analysed in the laboratory with nuclear
      and chloroplast markers. Using a Bayesian approach, > 90% of the samples could be
      assigned to one of two distinct clusters corresponding to previously described
      species, making it possible to estimate the genetic structure of each species and
      to identify cases of introgression. We argue that this blind procedure represents
      a first-choice rather than a fallback option whenever related taxa are
      investigated.

PMID- 17032254
TI  - Genetic structure at range edge: low diversity and high inbreeding in Southeast
      Asian mangrove (Avicennia marina) populations.
AB  - Understanding the genetic composition and mating systems of edge populations
      provides important insights into the environmental and demographic factors
      shaping species' distribution ranges. We analysed samples of the mangrove
      Avicennia marina from Vietnam, northern Philippines and Australia, with
      microsatellite markers. We compared genetic diversity and structure in edge
      (Southeast Asia, and Southern Australia) and core (North and Eastern Australia)
      populations, and also compared our results with previously published data from
      core and southern edge populations. Comparisons highlighted significantly reduced
      gene diversity and higher genetic structure in both margins compared to core
      populations, which can be attributed to very low effective population size,
      pollinator scarcity and high environmental pressure at distribution margins. The
      estimated level of inbreeding was significantly higher in northeastern
      populations compared to core and southern populations. This suggests that despite
      the high genetic load usually associated with inbreeding, inbreeding or even
      selfing may be advantageous in margin habitats due to the possible advantages of
      reproductive assurance, or local adaptation. The very high level of genetic
      structure and inbreeding show that populations of A. marina are functioning as
      independent evolutionary units more than as components of a metapopulation system
      connected by gene flow. The combinations of those characteristics make these
      peripheral populations likely to develop local adaptations and therefore to be of
      particular interest for conservation strategies as well as for adaptation to
      possible future environmental changes.

PMID- 17032255
TI  - Population structure within and between subspecies of the Mediterranean triplefin
      fish Tripterygion delaisi revealed by highly polymorphic microsatellite loci.
AB  - Although F(ST) values are widely used to elucidate population relationships, in
      some cases, when employing highly polymorphic loci, they should be regarded with
      caution, particularly when subspecies are under consideration. Tripterygion
      delaisi presents two subspecies that were investigated here, using 10
      microsatellite loci. A Bayesian approach allowed us to clearly identify both
      subspecies as two different evolutionary significant units. However, low F(ST)
      values were found between subspecies as a consequence of the large number of
      alleles per locus, while homoplasy could be disregarded as indicated by the
      standardized genetic distance G'(ST). Heterozygosity saturation was observed in
      highly polymorphic loci containing more than 15 alleles, and this threshold was
      used to define two loci pools. The less variable loci pool revealed higher
      genetic variance between subspecies, while the more variable pool showed higher
      genetic variance between populations. Furthermore, higher differentiation was
      also observed between populations using G'(ST) with the more variable loci.
      Nonetheless, a more reliable population structure within subspecies was obtained
      when all loci were included in the analyses. In T. d. xanthosoma, isolation by
      distance was detected between the eight analysed populations, and six genetically
      homogeneous clusters were inferred by Bayesian analyses that are in accordance
      with F(ST) values. The neighbourhood-size method also indicated rather small
      dispersal capabilities. In conclusion, in fish with limited adult and larval
      dispersal capabilities, continuous rocky habitat seems to allow contact between
      populations and prevent genetic differentiation, while large discontinuities of
      sand or deep-water channels seems to reduce gene flow.

PMID- 17032256
TI  - Evolutionary diversification of the bean beetle genus Callosobruchus (Coleoptera:
      Bruchidae): traits associated with stored-product pest status.
AB  - Despite the fact that many plant-feeding insects are pests, little effort has
      been made to identify key evolutionary trait transitions that allow taxa to
      acquire or lose pest status. A large proportion of species in the genus
      Callosobruchus are economically important pests of stored, dry postharvest beans
      of the tribe Phaseoleae. However, the evolution of this feeding habit is poorly
      understood. Here, we present a reconstruction of the phylogeny of the Asian and
      African Callosobruchus based on three mitochondrial genes, and assess which
      traits have been associated with the evolutionary origin or loss of ability to
      reproduce on dry beans. Our phylogenetic analysis showed that species group into
      the chinensis and the maculatus clades, which are also supported by genital
      morphology, and an additional paraphyletic group. Ancestral ability to use dry
      beans has been lost in the chinensis clade but acquired again in C. chinensis.
      Dry-bean use and host-plant use were both phylogenetically constrained and
      transitions in the two were significantly correlated. Host shifts from the
      subtribe Phaseolinae to Cajaninae were more common than the reverse and were more
      likely in species using young beans. The ability to use dry beans was more likely
      gained when using Phaseolinae hosts and promoted habitat shifts from tropical to
      temperate regions. Adaptation to arid climate was also associated with the
      ability to reproduce on dry beans and on Phaseolinae. Thus, our analysis suggests
      that physiological adaptations to an arid climate and to Phaseolinae hosts both
      render beetles predisposed to become pests of cultivated beans.

PMID- 17032257
TI  - Spatial population genetic structure and limited dispersal in a Rocky Mountain
      alpine stream insect.
AB  - Using the mitochondrial cytochrome oxidase I (COI) gene, we assessed the
      phylogeographic structure of Prosimulium neomacropyga, a black fly (Simuliidae)
      whose distribution in the US Southern Rockies ecoregion is limited to alpine
      tundra streams. Given high habitat specificity, lack of hydrological connection
      between streams, and a terrestrial environment restrictive to insect flight, we
      hypothesized limited gene flow. A spatially nested sampling design showed that
      grouping populations according to high-elevation 'islands' of alpine tundra
      (which typically include headwater streams of > 1 watershed) explained a
      significant proportion of genetic variation while grouping streams according to
      major watershed (across islands) did not. Nested clade analysis and isolation-by
      distance (IBD) relationships further implicated limited ongoing gene flow within
      but not among the isolated alpine islands. IBD was strong among five streams
      within an individual island using each of four alternative models of pairwise
      landscape connectivity for flying insects. Results of all landscape models were
      positively correlated, suggesting that straight-line distance is an acceptable
      surrogate for presumably more biologically meaningful connectivity measures in
      this system. IBD was significantly weaker across the entire study area, comprised
      of three separate islands. Overall, population structure was significant with
      F(ST) = 0.38, suggesting limited dispersal across a small spatial extent.

PMID- 17032259
TI  - Genetic admixture of burbot (Teleostei: Lota lota) in Lake Constance from two
      European glacial refugia.
AB  - The burbot, Lota lota, is the only freshwater species of the codfish family and
      has a Holarctic distribution. Pleistocene glaciations caused significant
      geographical differentiation in the past, but its life history characterized by
      winter spawning migrations over large distances is likely to homogenize
      populations by contemporary gene flow. We investigated the population genetic
      structure of 541 burbots from Lake Constance and adjacent Rhine and Danube
      tributaries in Europe using the entire mitochondrial DNA (mtDNA) control region
      and 11 microsatellites. Microsatellites revealed considerable population
      divergence (F(ST) = 0.26) and evidenced recent bottlenecks in two Central
      European rivers. In accordance to previous evidence two main phylogeographic
      lineages (Atlantic and Danubian) were found co-occurring at similar frequencies
      in Lake Constance, where they currently undergo random mating as indicated by
      microsatellites. The Danubian lineage contributed only a small proportion to the
      lake's mtDNA diversity, and probably expanded within the lake shortly after its
      formation approximately 10,000-15,000 BP. The larger Atlantic haplotype diversity
      suggested a population expansion older than the lake itself. Levels of admixture
      at microsatellite loci were less obvious due to their high variability, and
      coalescence methods were used to estimate past admixture proportions. Our results
      reinforce a model of a two-step colonization of Europe by burbot from an
      ancestral Danubian refuge, and confirm the persistence of a secondary Atlantic
      refuge, as proposed to exist for other freshwater fish. We conclude that the
      present-day burbot population in Lake Constance bears the genetic signature of
      both contemporary gene flow and historical separation events.

PMID- 17032260
TI  - Genetics of recent habitat contraction and reduction in population size: does
      isolation by distance matter?
AB  - Fragmentation and loss of natural habitats are recognized as major threats to
      contemporary flora and fauna. Detecting past or current reductions in population
      size is therefore a major aim in conservation genetics. Statistical methods
      developed to this purpose have tended to ignore the effects of spatial population
      structure. However in many species, individual dispersal is restricted in space
      and fine-scale spatial structure such as isolation by distance (IBD) is commonly
      observed in continuous populations. Using a simulation-based approach, we
      investigated how comparative and single-point methods, traditionally used in a
      Wright-Fisher (WF) population context for detecting population size reduction,
      behave for IBD populations. We found that a complex 'quartet' of factors was
      acting that includes restricted dispersal, population size (i.e. habitat size),
      demographic history, and sampling scale. After habitat reduction, IBD populations
      were characterized by a stronger inertia in the loss of genetic diversity than WF
      populations. This inertia increases with the strength of IBD, and decreases when
      the sampling scale increases. Depending on the method used to detect a population
      size reduction, a local sampling can be more informative than a sample scaled to
      habitat size or vice versa. However, IBD structure led in numerous cases to
      incorrect inferences on population demographic history. The reanalysis of a real
      microsatellite data set of skink populations from fragmented and intact
      rainforest habitats confirmed most of our simulation results.

PMID- 17032261
TI  - Analysis of spatial genetic structure in an expanding Pinus halepensis population
      reveals development of fine-scale genetic clustering over time.
AB  - We analysed the change of spatial genetic structure (SGS) of reproductive
      individuals over time in an expanding Pinus halepensis population. To our
      knowledge, this is the first empirical study to analyse the temporal component of
      SGS by following the dynamics of successive cohorts of the same population over
      time, rather than analysing different age cohorts at a single time. SGS is
      influenced by various factors including restricted gene dispersal,
      microenvironmental selection, mating patterns and the spatial pattern of
      reproductive individuals. Several factors that affect SGS are expected to vary
      over time and as adult density increases. Using air photo analysis, tree-ring
      dating and molecular marker analysis we reconstructed the spread of reproductive
      individuals over 30 years beginning from five initial individuals. In the early
      stages, genotypes were distributed randomly in space. Over time and with
      increasing density, fine-scale (< 20 m) SGS developed and the magnitude of
      genetic clustering increased. The SGS was strongly affected by the initial
      spatial distribution and genetic variation of the founding individuals. The
      development of SGS may be explained by fine-scale environmental heterogeneity and
      possibly microenvironmental selection. Inbreeding and variation in reproductive
      success may have enhanced SGS magnitude over time.

PMID- 17032258
TI  - Assessment of the diversity and species specificity of the mutualistic
      association between Epicephala moths and Glochidion trees.
AB  - The obligate mutualisms between flowering plants and their seed-parasitic
      pollinators constitute fascinating examples of interspecific mutualisms, which
      are often characterized by high levels of species diversity and reciprocal
      species specificity. The diversification in these mutualisms has been thought to
      occur through simultaneous speciation of the partners, mediated by tight
      reciprocal adaptation; however, recent studies cast doubt over this general view.
      In this study, we examine the diversity and species specificity of Epicephala
      moths (Gracillariidae) that pollinate Glochidion trees (Phyllanthaceae), using
      analysis of mitochondrial and nuclear gene sequences. Phylogenetic analysis of
      Epicephala moths associated with five Glochidion species in Japan and Taiwan
      reveal six genetically isolated species that are also distinguishable by male
      genital morphology: (i) two species specific to single host species (G.
      acuminatum and G. zeylanicum, respectively); (ii) two species that coexist on G.
      lanceolatum; and (iii) two species that share two, closely-related parapatric
      hosts (G. obovatum and G. rubrum). Statistical analysis shows that the two
      species associated with G. lanceolatum are not sister species, indicating the
      colonization of novel Glochidion host in at least one lineage. Behavioural
      observations suggest that all six species possess the actively-pollinating habit,
      thus none of the studied species has become a nonmutualistic 'cheater' that
      exploits the benefit resulting from pollination by other species. Our results
      parallel recent findings in ecologically similar associations, namely the fig-fig
      wasp and yucca-yucca moth mutualisms, and contribute to a more general
      understanding of the factors that determine ecological and evolutionary outcomes
      in these mutualisms.

PMID- 17032262
TI  - Geological history and within-island diversity: a debris avalanche and the
      Tenerife lizard Gallotia galloti.
AB  - Several processes have been described that could explain geographical variation
      and speciation within small islands, including fragmentation of populations
      through volcanic eruptions. Massive landslides, or debris avalanches, could cause
      similar effects. Here we analyse the potential impact of the 0.8 million-year-ago
      (Ma) Guimar valley debris avalanche on the phylogeography of the lizard Gallotia
      galloti on the Canary Island of Tenerife. Distributions of mitochondrial DNA
      lineages (based on cytochrome b sequences) were analysed on a 60-km southeastern
      coast transect centred on this area. Three main clades were detected, which can
      be divided into northern (one clade) and southern (two clades) groups that
      introgress across the valley. Maximum-likelihood estimates of migration rates
      (scaled for mutation rate) revealed highly asymmetric patterns, indicating that
      long-term gene flow into this region from both the northern and the southern
      populations greatly exceeded that in the opposite directions, consistent with
      recolonization of the area. The ancestral Tenerife node on the G. galloti tree is
      estimated at 0.80 Ma, matching closely with the geological estimate for the
      debris avalanche. Morphological variation (body dimensions and scalation) was
      also analysed and indicated a stepped cline in female scalation across the
      valley, although the patterns for male scalation and male and female body
      dimensions were not as clear. Together these findings provide support for the
      hypothesis that the debris avalanche has shaped the phylogeography of G. galloti
      and may even have been a primary cause of the within-island cladogenesis through
      population fragmentation and isolation. Current estimates of timing of island
      unification mean that the original hypothesis that within-island diversity is
      explained by the secondary contact of populations from the two ancient precursor
      islands of Teno and Anaga is less plausible for this and some other Tenerife
      species. Large-scale landslides have occurred on many volcanic islands, and so
      may have been instrumental in shaping within-island diversities.

PMID- 17032263
TI  - Contrasting patterns in genetic diversity following multiple invasions of fresh
      and brackish waters.
AB  - Biological invasions may combine the genetic effects of population bottlenecks
      and selection and thus provide valuable insight into the role of such processes
      during novel environmental colonizations. However, these processes are also
      influenced by multiple invasions, the number of individuals introduced and the
      degree of similarity between source and receiving habitats. The amphipod Gammarus
      tigrinus provides a useful model to assess these factors, as its invasion history
      has involved major environmental transitions. This species is native to the
      northwest Atlantic Ocean, although it invaded both brackish and freshwater
      habitats in the British Isles after introduction more than 65 years ago. It has
      also spread to similar habitats in Western Europe and, most recently, to Eastern
      Europe, the Baltic Sea, and the Laurentian Great Lakes. To examine sources of
      invasion and patterns of genetic change, we sampled populations from 13 native
      estuaries and 19 invaded sites and sequenced 542 bp of the mitochondrial COI
      gene. Strong native phylogeographical structure allowed us to unambiguously
      identify three allopatrically evolved clades (2.3-3.1% divergent) in invading
      populations, indicative of multiple introductions. The most divergent clades
      occurred in the British Isles and mainland Europe and were sourced from the St
      Lawrence and Chesapeake/Delaware Bay estuaries. A third clade was found in the
      Great Lakes and sourced to the Hudson River estuary. Despite extensive sampling,
      G. tigrinus did not occur in freshwater at putative source sites. Some European
      populations showed reduced genetic diversity consistent with bottlenecks,
      although selection effects cannot be excluded. The habitat distribution of clades
      in Europe was congruent with the known invasion history of secondary spread from
      the British Isles. Differences in salinity tolerance among lineages were
      suggested by patterns of habitat colonization by different native COI clades.
      Populations consisting of admixtures of the two invading clades were found
      principally at recently invaded fresh and brackish water sites in Eastern Europe,
      and were characterized by higher genetic diversity than putative source
      populations. Further studies are required to determine if these represent novel
      genotypes. Our results confirm that biological invasions need not result in
      diminished genetic diversity, particularly if multiple source populations, each
      with distinctive genetic composition, contribute to the founding populations.

PMID- 17032264
TI  - Temporal cline in a hybrid zone population between Fraxinus excelsior L. and
      Fraxinus angustifolia Vahl.
AB  - The two closely related ash species Fraxinus excelsior L. (common ash) and
      Fraxinus angustifolia Vahl (narrow-leaved ash) have a broad contact zone in
      France where they hybridize. However, little is known about the local structure
      of hybrid zone populations and the isolation mechanisms. We assessed the
      potential effect of floral phenology on the structure of a riparian ash hybrid
      zone population in central France. The distribution of flowering times was
      unimodal and lay between the flowering periods of the two species. Using
      microsatellite markers, we detected isolation by time, which has possibly
      originated from assortative mating. Multivariate analyses indicated that
      morphological variation is not distributed at random with respect to flowering
      times. Spatial autocorrelation analyses showed that temporal and spatial patterns
      were tightly linked. Interestingly, despite the fact that the population shows
      isolation by time, neighbourhood size and historical dispersal variance (sigma =
      63 m) are similar to those detected in pure stands of F. excelsior where
      individuals flower rather synchronously and hermaphrodites are not the most
      frequent sexual type. Trees flowering at intermediate dates, which comprised the
      majority of the population, produced on average more flowers and fruits. We
      detected no significant differences in floral parasite infections relative to
      reproductive timing, although there was a tendency for late flowering trees to
      suffer from more gall attack. We discuss the impact of temporal variation in
      fitness traits and their possible role in the maintenance of the hybrid zone.

PMID- 17032265
TI  - Worldwide phylogeography of the blacktip shark (Carcharhinus limbatus) inferred
      from mitochondrial DNA reveals isolation of western Atlantic populations coupled
      with recent Pacific dispersal.
AB  - Although many coastal shark species have widespread distributions, the genetic
      relatedness of worldwide populations has been examined for few species. The
      blacktip shark, (Carcharhinus limbatus), inhabits tropical and subtropical
      coastal waters throughout the world. In this study, we examined the genetic
      relationships of blacktip shark populations (n = 364 sharks) throughout the
      majority of the species' range using the entire mitochondrial control region
      (1067-1070 nucleotides). Two geographically distinct maternal lineages (western
      Atlantic, Gulf of Mexico, and Caribbean Sea clades, and eastern Atlantic, Indian,
      and Pacific Ocean clades) were identified and shallow population structure was
      detected throughout their geographic ranges. These findings indicate that a major
      population subdivision exists across the Atlantic Ocean, but not the Pacific
      Ocean. The historical dispersal of this widespread, coastal species may have been
      interrupted by the rise of the Isthmus of Panama. This scenario implies
      historical dispersal across the Pacific Ocean (supported by the recovery of the
      same common haplotype from the Philippines, Hawaii, and the Gulf of California
      reflecting recent/contemporary dispersal abilities) and an oceanic barrier to
      recent migration across the Atlantic. Genetic structure within the eastern
      Atlantic/Indo-Pacific (Phi(ST) = 0.612, P < 0.001) supports maternal philopatry
      throughout this area, expanding previous western Atlantic findings. Eastern
      Atlantic/Indo-Pacific C. limbatus control region haplotypes were paraphyletic to
      Carcharhinus tilstoni haplotypes in our maximum-parsimony analysis. The greater
      divergence of western Atlantic C. limbatus than C. tilstoni from eastern
      Atlantic/Indo-Pacific C. limbatus reflects the taxonomic uncertainty of western
      Atlantic C. limbatus.

PMID- 17032266
TI  - Menage a trois on Macquarie Island: hybridization among three species of fur seal
      (Arctocephalus spp.) following historical population extinction.
AB  - Human-induced changes to natural systems can cause major disturbances to
      fundamental ecological and population processes and result in local extinctions
      and secondary contacts between formerly isolated species. Extensive fur seal
      harvesting during the nineteenth century on Macquarie Island (subantarctic)
      resulted in extinction of the original population. Recolonization by three
      species has been slow and complex, characterized by the establishment of breeding
      groups of Antarctic and subantarctic fur seals (Arctocephalus gazella and
      Arctocephalus tropicalis) and presumed nonbreeding (itinerant) male New Zealand
      fur seals (Arctocephalus forsteri). One thousand and seven pups from eight annual
      cohorts (1992-2003) were analysed using mitochondrial control region data (RFLP)
      and 10 microsatellite loci to estimate species composition and hybridization.
      Antarctic fur seals predominated, but hybridization occurred between all three
      species (17-30% of all pups). Involvement of New Zealand fur seals was unexpected
      as females are absent and males are not observed to hold territories during the
      breeding season. The proportion of hybrids in the population has fallen over
      time, apparently owing to substantial influxes of pure Antarctic and subantarctic
      individuals and non-random mating. Over 50% of New Zealand hybrids and 43% of
      Antarctic-subantarctic hybrids were not F(1), which indicates some degree of
      hybrid reproductive success, and this may be underestimated: simulations showed
      that hybrids become virtually undetectable by the third generation of
      backcrossing. While human impacts seem to have driven novel hybridization in this
      population, the present 'time slices' analysis suggests some biological
      resistance to complete homogenization.

PMID- 17032267
TI  - Phylogeography and population structure of thornback rays (Raja clavata L.,
      Rajidae).
AB  - The phylogeography of thornback rays (Raja clavata) was assessed from European
      waters, using five nuclear microsatellite loci and mitochondrial cytochome b
      sequences. Strong regional differentiation was found between the Mediterranean
      basin, the Azores and the European continental shelf. Allelic and haplotype
      diversities were high in Portuguese populations, consistent with the existence of
      a refugium along the Iberian Peninsula. Unexpectedly, high diversity was also
      found in the English Channel/North Sea area. The lowest genetic diversity was
      found in the Black Sea. Populations sampled from the Mediterranean, Adriatic and
      Black Seas were characterized by a single mitochondrial haplotype. This haplotype
      was also the most ancestral and widespread outside of the Mediterranean basin
      except for the Azores. Populations from the Azores were dominated by a second
      ancestral haplotype which was shared with British populations. Results from
      multidimensional scaling, amova and nested clade analysis indicate that British
      waters are a secondary contact zone recolonized from at least two refugia--one
      around the Iberian Peninsula and one possibly in the Azores. Links to a potential
      refugium known as the Hurd Deep, between Cornwall and Brittany, are discussed.
      Finally, a historical demographic analysis indicates that thornback ray
      populations started to expand between 580,000 and 362,000 years ago, which
      suggests that the Last Glacial Maximum (20,000 years ago) had mainly affected the
      distribution of populations rather than population size.

PMID- 17032269
TI  - Towards unbiased parentage assignment: combining genetic, behavioural and spatial
      data in a Bayesian framework.
AB  - Inferring the parentage of a sample of individuals is often a prerequisite for
      many types of analysis in molecular ecology, evolutionary biology and
      quantitative genetics. In all but a few cases, the method of parentage assignment
      is divorced from the methods used to estimate the parameters of primary interest,
      such as mate choice or heritability. Here we present a Bayesian approach that
      simultaneously estimates the parentage of a sample of individuals and a wide
      range of population-level parameters in which we are interested. We show that
      joint estimation of parentage and population-level parameters increases the power
      of parentage assignment, reduces bias in parameter estimation, and accurately
      evaluates uncertainty in both. We illustrate the method by analysing a number of
      simulated test data sets, and through a re-analysis of parentage in the
      Seychelles warbler, Acrocephalus sechellensis. A combination of behavioural,
      spatial and genetic data are used in the analyses and, importantly, the method
      does not require strong prior information about the relationship between
      nongenetic data and parentage.

PMID- 17032270
TI  - Refugia of Potentilla matsumurae (Rosaceae) located at high mountains in the
      Japanese archipelago.
AB  - Molecular phylogeographic studies have revealed the genetic patterns and glacial
      interglacial history of many plant and animal species. To infer the Quaternary
      history of alpine plants in the Japanese archipelago, which is poorly known, we
      investigated 203 individuals of Potentilla matsumurae and its varieties from 22
      populations. We found 11 haplotypes based on approximately 1400 bp of two
      intergenetic spacers in chloroplast DNA (trnT-L and rpl20-rps20). The
      distribution of these haplotypes was geographically structured, which was
      supported by haplotype composition, principal component analysis, and unweighted
      pair group method with arithmetic mean (UPGMA), and N(ST) (0.71) was
      significantly greater than G(ST) (0.68). In addition to the positive correlation
      between genetic and geographic distance (Mantel test, r = 0.497, P < 0.001), an
      abrupt genetic change was detected between mountains in central Honshu and the
      Tohoku region. This genetic boundary was further supported by analysis of
      molecular variance (AMOVA), and high variation (54.0%) was explained by
      differences on either side of this boundary. Moreover, haplotypes in central
      Honshu were thought to have diverged, based on an outgroup comparison. These
      results suggest that mountains in central Honshu served as refugia during the
      Quaternary climatic oscillation, although the results could not reveal the
      history of most mountains in the Tohoku region and Hokkaido. Nevertheless,
      following floristic studies, our results indicate that alpine plants in Japan
      experienced a history different from that in Europe; i.e. they retreated into
      refugia during warm periods to avoid forest development, rather than glaciers.

PMID- 17032268
TI  - Multiple origins of cultivated grapevine (Vitis vinifera L. ssp. sativa) based on
      chloroplast DNA polymorphisms.
AB  - The domestication of the Eurasian grape (Vitis vinifera ssp. sativa) from its
      wild ancestor (Vitis vinifera ssp. sylvestris) has long been claimed to have
      occurred in Transcaucasia where its greatest genetic diversity is found and where
      very early archaeological evidence, including grape pips and artefacts of a 'wine
      culture', have been excavated. Whether from Transcaucasia or the nearby Taurus or
      Zagros Mountains, it is hypothesized that this wine culture spread southwards and
      eventually westwards around the Mediterranean basin, together with the
      transplantation of cultivated grape cuttings. However, the existence of
      morphological differentiation between cultivars from eastern and western ends of
      the modern distribution of the Eurasian grape suggests the existence of different
      genetic contribution from local sylvestris populations or multilocal selection
      and domestication of sylvestris genotypes. To tackle this issue, we analysed
      chlorotype variation and distribution in 1201 samples of sylvestris and sativa
      genotypes from the whole area of the species' distribution and studied their
      genetic relationships. The results suggest the existence of at least two
      important origins for the cultivated germplasm, one in the Near East and another
      in the western Mediterranean region, the latter of which gave rise to many of the
      current Western European cultivars. Indeed, over 70% of the Iberian Peninsula
      cultivars display chlorotypes that are only compatible with their having derived
      from western sylvestris populations.

PMID- 17032271
TI  - Genetic diversity and phylogeography of the Apennine yellow-bellied toad Bombina
      pachypus, with implications for conservation.
AB  - Genetic variation was investigated in 17 populations of the Italian endemic
      Apennine yellow-bellied toad using both mitochondrial (598 bp of the cytochrome b
      gene) and nuclear (21 allozyme loci) markers. Populations from central Calabria
      (southern Italy) showed the highest levels of intrapopulation genetic variation,
      whereas samples located north of this region were nearly lacking in variation.
      This appears to be a typical pattern of 'southern richness and northern purity',
      usually attributed to the prolonged population stability within southern refugia
      coupled with the loss of variation during postglacial northward expansion.
      However, the overall pattern of genetic variation observed has a strong
      geographical component, suggesting two Calabrian plains, Catanzaro and Crati
      Sibari, as historical barriers to dispersal separating three population groups.
      These findings cannot be explained by the prolonged stability of southern
      populations alone, and suggest that the southern richness has been at least in
      part shaped by allopatric differentiation within the refugial range, followed by
      intermixing of previously differentiated lineages. From a conservation
      standpoint, Calabria is the major genetic diversity reservoir for this species,
      thus deserving particular conservation efforts. Furthermore, although the low
      intrapopulation genetic variation outside Calabria appears to be of clear
      historical origin, evidence of a current reduction of gene flow suggests that
      human disturbance has also played a part, particularly in the anthropogenic
      impacted Volturno river drainage basin.

PMID- 17032272
TI  - Hybridization between mtDNA-defined phylogeographic lineages of black ratsnakes
      (Pantherophis sp.).
AB  - Phylogeographic analyses using mitochondrial DNA (mtDNA) have revealed many
      examples of apparently deep historical subdivisions ('phylogroups') within many
      vertebrates. It remains unclear whether these phylogroups represent independently
      evolving, adaptively differentiated lineages or groups that show little
      functional differentiation and, hence, will merge on contact. Here, we use mtDNA
      sequence data to evaluate the phylogeographic relationships between two of the
      northernmost populations of black ratsnakes (Pantherophis obsoletus complex) in
      Ontario, Canada and previously analysed populations in the United States. We then
      use population-level analyses to evaluate the level of adaptive divergence
      between previously established mtDNA phylogroups. Phylogenetic analyses show that
      southern Ontario snakes have mtDNA haplotypes that fall within the Central mtDNA
      phylogroup, as designated by Burbrink et al. (2000). In contrast, snakes in
      eastern Ontario carry either Central or Eastern-specific haplotypes. Within the
      hybrid region, we found highly variable frequencies of mtDNA haplotypes among
      isolated sub-populations, no association between variation in cytonuclear (mtDNA)
      and nuclear (microsatellite DNA) markers, no difference in survival or
      reproductive success among snakes with different mtDNA haplotypes, and no effect
      of mate similarity in mtDNA on female clutch size. These results argue that the
      Eastern and Central phylogroups have merged in this region, likely due to a lack
      of adaptive differentiation between individuals in each lineage. Hence, in these
      snakes, phylogeographic structure in mtDNA is more a reflection of historical
      isolation rather than adaptive divergence. The observed reticulation between
      lineages and lack of evidence for hybrid disgenesis also bears on the
      classification of these lineages as distinct species.

PMID- 17032273
TI  - Immigration, species radiation and extinction in a highly diverse songbird
      lineage: white-eyes on Indian Ocean islands.
AB  - Molecular phylogenetic hypotheses of species-rich lineages in regions where
      geological history can be reliably inferred may provide insights into the scale
      of processes driving diversification. Here we sample all extant or recently
      extinct white-eye (Zosterops) taxa of the southwest Indian Ocean, combined with
      samples from all principal continental lineages. Results support a high dispersal
      capability, with at least two independent continental sources for white-eyes of
      the region. An early (within 1.8 million years ago) expansion into the Indian
      Ocean may have originated either from Asia or Africa; the three resulting
      lineages show a disparate distribution consistent with considerable extinction
      following their arrival. Africa is supported as the origin of a later expansion
      into the region (within 1.2 million years ago). On two islands, a pair of
      Zosterops species derived from independent immigrations into the Indian Ocean co
      occur or may have formerly co-occurred, providing strong support for their origin
      by double-island colonization rather than within-island (sympatric or
      microallopatric) speciation. On Mauritius and La Reunion, phylogenetic placement
      of sympatric white-eyes allow us to rule out a scenario in which independent
      within-island speciation occurred on both islands; one of the species pairs must
      have arisen by double colonization, while the other pair is likely to have arisen
      by the same mechanism. Long-distance immigration therefore appears to be
      responsible for much of the region's white-eye diversity. Independent
      immigrations into the region have resulted in lineages with mutually exclusive
      distributions and it seems likely that competition with congeneric species,
      rather than arrival frequency, may limit present-day diversity.

PMID- 17032274
TI  - Hybridization between subspecies of waterbuck (Kobus ellipsiprymnus) in zones of
      overlap with limited introgression.
AB  - Two subspecies of waterbuck (Kobus ellipsiprymnus), common (Kobus ellipsiprymnus
      ellipsiprymnus) and defassa (Kobus ellipsiprymnus defassa), are recognized based
      on differences in rump pattern, coat colour and geographical distribution. These
      forms are parapatrically distributed with an area of range overlap in East
      Africa, where phenotypically intermediate populations occur. Variation in 478 bp
      of the mitochondrial DNA control region and 14 polymorphic microsatellite loci
      were used to describe the genetic structure and phylogeographical pattern of the
      species, and to assess if the intermediate populations are the results of
      hybridization. In total, 186 individuals from 11 localities were analysed. A high
      degree of genetic differentiation was found between subspecies, although this was
      most evident from the microsatellite data. Hybridization was suggested in the
      phenotypically and geographically intermediate Nairobi NP population in Kenya. A
      neighbour-joining (NJ) tree based on microsatellite population genetic distances
      grouped Nairobi between the common and defassa populations, and a Bayesian
      analysis clearly showed introgression. Individuals sampled in Samburu NP, Kenya,
      had a common waterbuck phenotype, but introgression was suggested by both
      markers. Although a high degree of maternal defassa input was indicated from the
      sequence data, the Samburu population grouped with the common waterbuck in the
      microsatellite population genetic distance tree, with high support. Analyses of
      linkage disequilibrium and maximum-likelihood estimates of genetic drift
      suggested that admixture between subspecies is a recent event. The fact that
      introgression is limited between subspecies could be caused by chromosomal
      differences, hindering gene flow between common and defassa waterbuck.

PMID- 17032275
TI  - Temporal recruitment patterns and gene flow in kelp rockfish (Sebastes
      atrovirens).
AB  - Pelagic dispersal of marine organisms provides abundant opportunity for gene flow
      and presumably inhibits population genetic divergence. However, ephemeral, fine
      scale, temporal and spatial genetic heterogeneity is frequently observed in
      settled propagules of marine species that otherwise exhibit broad-scale genetic
      homogeneity. A large variance in reproductive success is one explanation for this
      phenomenon. Here, genetic analyses of 16 microsatellite loci are used to examine
      temporal patterns of variation in young-of-year kelp rockfish (Sebastes
      atrovirens) recruiting to nearshore habitat in Monterey Bay, California, USA.
      Population structure of adults from central California is also evaluated to
      determine if spatial structure exists and might potentially contribute to
      recruitment patterns. Genetic homogeneity was found among 414 young-of-year
      sampled throughout the entire 1998 recruitment season. No substantial adult
      population structure was found among seven populations spanning 800 km of
      coastline that includes the Point Conception marine biogeographic boundary.
      Comparison of young-of-year and adult samples revealed no genetic differentiation
      and no measurable reduction in genetic variation of offspring, indicating little
      variance in reproductive success and no reduction in effective population size
      for this year class. Simulation analyses determined that the data set was
      sufficiently powerful to detect both slight population structure among adults and
      a small reduction in effective number of breeders contributing to this year
      class. The findings of high gene flow and low genetic drift have important
      implications for fisheries management and conservation efforts.

PMID- 17032276
TI  - Postcopulatory inbreeding avoidance by female crickets only revealed by molecular
      markers.
AB  - Multiple mating is thought to provide an opportunity for females to avoid the
      costs of genetic incompatibility by postcopulatory selection of compatible sperm
      haplotypes. Few studies have tested the genetic incompatibility hypothesis
      directly. Here we experimentally manipulated the compatibility of females with
      their mates using the gryllid cricket Teleogryllus oceanicus. We recorded the
      hatching success of eggs laid by females mated with two nonsibling males, two
      siblings, or one nonsibling male and one sibling. In contrast with two previous
      studies on crickets that have adopted this approach, the hatching success of eggs
      did not differ between females mated with two full siblings and females mated
      with two unrelated males, indicating that embryo viability was not a cost of
      inbreeding in this species. We assigned paternity to offspring produced by
      females mated to both a sibling and a nonsibling male using microsatellite
      markers. As in previous studies of this species, we were unable to detect any
      difference in the proportion of offspring sired by the 1st and the 2nd male to
      mate with a female when females were unrelated to their mates. However, in our
      experimental matings the proportion of offspring sired by the nonsibling male
      depended on his sequence position. Paternity was biased toward the nonsibling
      male when he mated first. Our data show that molecular analyses of paternity are
      essential to detect subtle mechanisms of postcopulatory sexual selection.

PMID- 17032277
TI  - Consequences of group fission for the patterns of relatedness among rhesus
      macaques.
AB  - When mammalian social groups exceed their optimal size, they often tend to split.
      In view of the potential evolutionary benefits, it should be more advantageous
      for animals to stay with kin, rather than nonkin, during such fission events. In
      the present study, the spontaneous fission of two social groups, R and S, of
      rhesus macaques living on Cayo Santiago, Puerto Rico, provided the opportunity to
      compare the kinship structure of the corresponding parent and daughter groups,
      using information on both maternal and paternal relatedness. In both instances,
      maternal half-siblings and pairs of animals from the same family were
      significantly more prevalent in the fission products than in the parent group.
      During the split of group R, significantly more paternal half-siblings stayed in
      the remnants of the parent group than joined the seceding group. Our findings are
      compatible with previous behavioural studies demonstrating that female primates
      bias their social behaviour more to maternal than to paternal kin, but that both
      types of half-siblings prefer each other more than unrelated animals. It remains
      to be clarified by future research, however, whether the observed co-segregation
      of paternal half-sibs in our study reflects active choice or is a by-product of
      the group-specific kin structures, prior to fission.

PMID- 17032278
TI  - Immune response of nestling warblers varies with extra-pair paternity and
      temperature.
AB  - Extra-pair mating is widespread in birds, but its adaptive function remains
      unclear. It is often suggested that females obtain superior genes for their
      offspring as a consequence of extra-pair mating, but the evidence is limited. In
      this study, we examined the hypothesis that extra-pair mating provides females
      with offspring that have superior immune responses. We found that the T-cell
      mediated immune response of extra-pair young was stronger than that of within
      pair young in common yellowthroats (Geothlypis trichas). This paternity effect
      occurred when we compared all nestlings in the population, as well as in
      comparisons of both paternal and maternal half-siblings. Paternal half-siblings
      had a stronger immune response when they were produced with extra-pair females
      than with the male's social mate, which suggests that the greater immune response
      of extra-pair young was caused by nonadditive (compatible) genetic effects.
      However, these patterns were only significant in the colder of 2 years. Immune
      response was related positively to air temperature and nestlings had a stronger
      immune response in the warmer year. We suggest that such environmental variation
      could obscure the genetic benefits of extra-pair mating.

PMID- 17032279
TI  - Genetic tagging reveals extreme site fidelity in territorial male Antarctic fur
      seals Arctocephalus gazella.
AB  - Genetic tagging, the identification of individuals using their genotypes,
      provides a powerful tool for studying animals that are difficult to observe or
      identify using conventional techniques. However, despite being widely adopted by
      conservation biologists, the full potential of this approach has yet to be
      realized. Here we used genetic recapture data to quantify male site fidelity at a
      colony of Antarctic fur seals where an aerial walkway provides unprecedented
      access and individual positions are determined daily to 1 m accuracy. Because
      males are too large and aggressive to be captured and fitted with conventional
      tags, we remotely collected 770 tissue samples over eight consecutive seasons and
      used nine-locus microsatellite genotypes to reveal 306 genetic recaptures among
      464 unique individuals. Within seasons, males are highly site-faithful, with any
      movements that occur tending to take place before the period when females come
      into oestrus. Of those males that return to breed over successive seasons, almost
      half return to within a body length of where they were before. The discovery of
      such extreme site faithfulness has implications for the population structure and
      mating system of fur seals and potentially other colonially breeding species.

PMID- 17032280
TI  - Diversity of microcystin genotypes among populations of the filamentous
      cyanobacteria Planktothrix rubescens and Planktothrix agardhii.
AB  - Microcystins (MCs) are toxic heptapeptides that are produced by filamentous
      cyanobacteria Planktothrix rubescens and Planktothrix agardhii via nonribosomal
      peptide synthesis. MCs share a common structure cyclo (-D-Alanine(1)-L-X(2)- D
      erythro-beta-iso-aspartic acid(3)-L-Z(4)-Adda(5)-D-Glutamate(6)- N-methyl
      dehydroalanine(7)) where X(2) and Z(2) are variable L-amino acids in positions 2,
      4 of the molecule. Part of the mcyB gene (1,451 bp) that is involved in the
      activation of the X(2) amino acid during MC synthesis was sequenced in 49 strains
      containing different proportions of arginine, homotyrosine, and leucine in
      position 2 of the MC molecule. Twenty-five genotypes were found that consisted of
      eight genotype groups (A-H, comprising 2-11 strains) and 17 unique genotypes. P.
      rubescens and P. agardhii partly consisted of the same mcyB genotypes. The
      occurrence of numerous putative recombination events that affected all of the
      genotypes can explain the conflict between taxonomy and mcyB genotype
      distribution. Genotypes B (homotyrosine and leucine in X(2)) and C (arginine in
      X(2)) showed higher nonsynonymous/synonymous (d(N)/d(S)) substitution ratios
      implying a relaxation of selective constraints. In contrast, other genotypes
      (arginine, leucine, homotyrosine) showed lowest d(N)/d(S) ratios implying
      purifying selection. Restriction fragment length polymorphism (RFLP) revealed the
      unambiguous identification of mcyB genotypes, which are indicative of variable
      X(2) amino acids in eight populations of P. rubescens in the Alps (Austria,
      Germany, and Switzerland). The populations were found to differ significantly in
      the proportion of specific genotypes and the number of genotypes that occurred
      over several years. It is concluded that spatial isolation might favour the
      genetic divergence of microcystin synthesis in Planktothrix spp.

PMID- 17032281
TI  - Can quantification of faecal occult blood predetermine the need for colonoscopy
      in patients at risk for non-syndromic familial colorectal cancer?
AB  - BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial
      colorectal neoplasia undergo colonoscopic surveillance at intervals determined by
      clinically ascertained protocols. The quantitative immunochemical faecal occult
      blood test for human haemoglobin is specific and sensitive for significant
      colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine
      immunochemical faecal occult blood test efficacy for identifying significant
      neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We
      retrospectively identified consecutive at-risk patients who provided three
      immunochemical faecal occult blood tests before colonoscopy. Quantitative
      haemoglobin analysis was performed by the OC-MICRO automated instrument using the
      100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients
      undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non
      advanced adenoma. The immunochemical faecal occult blood test was positive in 31
      patients (12.3%). Sensitivity, specificity, positive and negative predictive
      values for cancer were: 100%, 90%, 16% and 100%, and for all significant
      neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal
      cancers and 74% of all significant neoplasia would have been identified by this
      one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A
      sensitive, non-invasive, interval screening test might be useful to predetermine
      the need for colonoscopy in this at-risk population and minimize unnecessary
      examinations. This favourable retrospective evaluation will be extended to a
      prospective study.

PMID- 17032282
TI  - Third-line rescue therapy with levofloxacin is more effective than rifabutin
      rescue regimen after two Helicobacter pylori treatment failures.
AB  - BACKGROUND: In patients with a first eradication failure, a second (rescue)
      therapy still fails in > 20% of cases. AIM: To compare rifabutin and levofloxacin
      rescue regimens in patients with two consecutive Helicobacter pylori eradication
      failures. METHODS: Patients, in whom first treatment with omeprazole
      clarithromycin-amoxicillin and a second trial with omeprazole-bismuth
      tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics)
      had failed, received 10 days of treatment with either rifabutin (150 mg b.d.) or
      levofloxacin (500 mg b.d.), plus amoxicillin (1 g b.d.) and omeprazole (20 mg
      b.d.). Cure rates were evaluated by the (13)C-urea breath test. RESULTS: Twenty
      patients received rifabutin, and 20 levofloxacin. All the patients returned for
      follow-up. Compliance in the rifabutin group was 100%. Four patients in the
      levofloxacin group did not take the medication correctly (in two cases due to
      adverse effects: myalgia and rash). Side effects in the rifabutin and
      levofloxacin groups were reported in 60% and 50% of the cases, respectively. Five
      patients (25%) treated with rifabutin presented with leucopenia, and six (30%)
      treated with levofloxacin presented with myalgias. Per-protocol cure rates were
      45% (95% confidence interval, 26-66%) in the rifabutin group, and 81% (57-93%) in
      the levofloxacin group (P < 0.05). Intention-to-treat cure rates were, 45% (26
      66%) and 85% (64-95%), respectively (P < 0.01). CONCLUSIONS: After two previous
      H. pylori eradication failures, a 10-day triple levofloxacin-based rescue regimen
      is more effective than the same regimen with rifabutin.

PMID- 17032283
TI  - Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter
      pylori treatment in children: a randomized placebo controlled trial.
AB  - BACKGROUND: Helicobacter pylori eradication fails in about 25-30% of children,
      particularly because of the occurrence of resistance to antibiotics and side
      effects. AIM: To determine whether adding the Lactobacillus reuteri to an anti-H.
      pylori regimen could help to prevent or minimize the gastrointestinal side
      effects burden in children. METHODS: Forty H. pylori-positive children (21 males;
      median age: 12.3 years) were consecutively treated with 10-day sequential therapy
      [omeprazole + amoxycillin for 5 days, and omeprazole + clarithromycin +
      tinidazole for other 5 days] and blindly randomized to receive either L. reuteri
      ATCC 55730 (10(8) CFU) or placebo. All children completed the Gastrointestinal
      Symptom Rating Scale (GSRS) at entry, during and after treatment. H. pylori
      status was assessed after 8 weeks by (13)C-urea breath test. RESULTS: Overall, in
      all probiotic supplemented children when compared with those receiving placebo
      there was a significant reduction of GSRS score during eradication therapy (4.1
      +/- 2 vs. 6.2 +/- 3; P < 0.01) and at the end of follow-up (3.2 +/- 2 vs. 5.8 +/-
      3.4; P < 0.009). Overall, children receiving L. reuteri report less symptoms than
      those receiving placebo. CONCLUSION: L. reuteri is capable of reducing frequency
      and intensity of antibiotic-associated side-effects during eradication therapy
      for H. pylori.

PMID- 17032284
TI  - Corpus-predominant gastritis as a risk factor for false-negative 13C-urea breath
      test results.
AB  - BACKGROUND: Urea breath test sensitivity seems affected by increased intragastric
      acidity during therapy with antisecretory drugs. Intragastric pH is increased in
      patients with corpus gastritis with/without atrophy. AIM: To test the hypothesis
      that urea breath test results may also be affected by this gastritis phenotype.
      METHODS: 123 untreated patients underwent gastroscopy plus biopsies and
      intragastric pH measurement. The study included 82 endoscopically proven
      Helicobacter pylori-positive patients who were offered urea breath test with an
      acidic meal. Histological findings, urea breath test results and intragastric pH
      were compared in 66 of the subjects. RESULTS: 21 of 66 (31.8%) patients had a
      false-negative urea breath test. In these patients corpus-predominant gastritis
      (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001)
      were more frequent than in patients with true-positive urea breath test.
      Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P =
      0.001). In a multivariate analysis, the only risk factor for a false-negative
      urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95%
      CI: 1.1-27). There was a negative correlation between the intragastric pH and the
      delta over baseline values (r = -0.378; P = 0.0023). CONCLUSIONS: Our results
      support the hypothesis that the pattern of gastritis can affect the sensitivity
      of urea breath test, and suggest that patients with corpus-predominant gastritis
      have a high risk of false-negative urea breath test results.

PMID- 17032285
TI  - A comparative study of intragastric acidity during post-breakfast and pre-dinner
      administration of low-dose proton pump inhibitors: a randomized three-way
      crossover study.
AB  - BACKGROUND: The absorption and bioavailability of proton pump inhibitors is
      influenced by food intake. Proton pump inhibitors bind to the parietal cell
      active proton pump, which is maximally stimulated after dinner: usually the
      largest meal of the day. However, it has not been fully clarified whether the
      efficacy of proton pump inhibitors differs between post-breakfast and pre-dinner
      dosing. AIM: To perform a pH-monitoring study to clarify this issue for two low
      dose proton pump inhibitors. SUBJECTS AND METHODS: The subjects were 20 healthy
      male volunteers (seven Helicobacter pylori-positive and 13 H. pylori-negative),
      who were divided into two groups of 10 and administered 15 mg lansoprazole or 10
      mg rabeprazole, respectively. All subjects underwent ambulatory intragastric 24-h
      pH- monitoring under three conditions allocated randomly: (i) without medication,
      (ii) seventh day of post-breakfast administration and (iii) eighth day of pre
      dinner administration of each drug. RESULTS: There was no significant difference
      in the percentage time during which pH > or =4.0 in the 24-h period between post
      breakfast and pre-dinner administration of both drugs (56.6% vs. 55.8%; P =
      0.557), although intragastric acidity during administration of both drugs was
      significantly lower than that without medication. CONCLUSIONS: The timing of drug
      administration does not significantly influence the efficacy of low-dose proton
      pump inhibitors.

PMID- 17032286
TI  - Outcome of peptic ulcer bleeding among users of traditional non-steroidal anti
      inflammatory drugs and selective cyclo-oxygenase-2 inhibitors.
AB  - BACKGROUND: Few data exist on the impact of non-steroidal anti-inflammatory drug
      use on peptic ulcer outcome. AIM: To examine the 30-day mortality from peptic
      ulcer bleeding associated with the use of traditional non-steroidal anti
      inflammatory drugs and newer selective cyclo-oxygenase-2 inhibitors. METHODS:
      Cohort study of patients with a first hospitalization for peptic ulcer bleeding
      in three Danish counties between 1991 and 2003. Data on pre-admission non
      steroidal anti-inflammatory drug use, use of other ulcer-related drugs and
      comorbidities were obtained from population-based registries. Follow-up data on
      mortality were obtained from the Danish Civil Registry System. RESULTS: Of 7,232
      patients hospitalized for peptic ulcer bleeding, 28% were current non-steroidal
      anti-inflammatory drug users. Thirty-day mortality was 11% overall, and 13% among
      current non-steroidal anti-inflammatory drug users. Compared with never-use, the
      adjusted 30-day mortality rate ratios were 1.4 (95% CI: 1.1-1.9) for current use
      of non-steroidal anti-inflammatory drugs alone and 1.3 (95% CI: 1.0-1.7) for
      current use combined with other ulcer-related drugs. For users of celecoxib,
      alone and in combination, adjusted mortality rate ratios were 1.4 (95% CI: 0.5
      3.9) and 2.0 (95% CI: 1.2-3.5), and for users of rofecoxib, 1.2 (95% CI: 0.4-3.9)
      and 0.9 (95% CI: 0.5-1.6). CONCLUSION: Among patients hospitalized with peptic
      ulcer bleeding, use of non-steroidal anti-inflammatory drugs, including some
      newer cyclo-oxygenase-2 inhibitors, is associated with increased short-term
      mortality.

PMID- 17032288
TI  - Polymorphisms in the angiotensin converting enzyme gene and growth in the first
      year of life.
AB  - Abnormal patterns of fetal and infant growth have been associated with an
      increased risk of cardiovascular disease in adulthood. Catch-up growth during the
      first year of life has been associated with a higher prevalence of type 2
      diabetes mellitus, whereas a lack of catch-up growth tracks with a risk of
      hypertension. The role of genetic factors influencing both growth and blood
      pressure have not been explored. We genotyped cord blood samples from 530
      singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of
      1650 pregnancies, and related polymorphism in the angiotensin converting enzyme
      (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth
      and at age of 1 year. ACE genotype did not significantly influence size at birth,
      although there was a greater proportion of individuals with the D/D genotype born
      with a birth weight less than the 10th centile (P=0.004). The ACE I/I genotype
      was significantly associated with higher weight (p=0.001), body mass index
      (p=0.001) and mid arm circumference (p=0.001) at 1 year of age compared to the
      ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch-up
      (gain from birth size of >or=0.6 Standard Deviation Score) in weight (p=0.04),
      body mass index (p=0.03) and mid arm circumference (p=0.03) compared to the D/D
      group, the majority of which showed no change or catch-down. The I/D genotype was
      distributed equally across the catch up/catch down/no change categories. The
      effect was more marked in males, but ACE genotype and sex of the infant
      contributed independently to mid arm circumference measurements and there was no
      interaction between the two. There was no effect of maternal or paternal ACE
      genotype on birth size. In a multiple linear regression model ACE genotype,
      socioeconomic status and sex of the infant explained 10.9% of the variance in
      body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is
      associated with a higher weight and body mass index SDS at 1 year of age, along
      with catch-up in terms of these measures from birth to 1 year. The D/D genotype
      is associated with a greater proportion of babies, born at term, that at small
      for gestational age. These results suggest that due consideration should be given
      to the underlying genotype of an individual when evaluating the association of
      early human growth with the development of risk factors for cardiovascular
      disease. The observation of independent effects of genotype, sex of the
      individual and socioeconomic status on postnatal growth suggests the need to
      develop methodologies for the integration of genetic and environmental factors in
      causality modelling.

PMID- 17032287
TI  - Mixed-effects logistic approach for association following linkage scan for
      complex disorders.
AB  - An association study to identify possible causal single nucleotide polymorphisms
      following linkage scanning is a popular approach for the genetic dissection of
      complex disorders. However, in association studies cases and controls are assumed
      to be independent, i.e., genetically unrelated. Choosing a single affected
      individual per family is statistically inefficient and leads to a loss of power.
      On the other hand, because of the relatedness of family members, using affected
      family members and unrelated normal controls directly leads to false-positive
      results in association studies. In this paper we propose a new approach using
      mixed-model logistic regression, in which associations are performed using family
      members and unrelated controls. Thus, the important genetic information can be
      obtained from family members while retaining high statistical power. To examine
      the properties of this new approach we developed an efficient algorithm, to
      simulate environmental risk factors and the genotypes at both the disease locus
      and a marker locus with and without linkage disequilibrium (LD) in families.
      Extensive simulation studies showed that our approach can effectively control the
      type-I error probability. Our approach is better than family-based designs such
      as TDT, because it allows the use of unrelated cases and controls and uses all of
      the affected members for whom DNA samples are possibly already available. Our
      approach also allows the inclusion of covariates such as age and smoking status.
      Power analysis showed that our method has higher statistical power than recent
      likelihood ratio-based methods when environmental factors contribute to disease
      susceptibility, which is true for most complex human disorders. Our method can be
      further extended to accommodate more complex pedigree structures.

PMID- 17032289
TI  - Computing power in case-control association studies through the use of quadratic
      approximations: application to meta-statistics.
AB  - In the framework of case-control studies many different test statistics are
      available to measure the association of a marker with a given disease.
      Nevertheless, choosing one particular statistic can lead to very different
      conclusions. In the absence of a consensus for this choice, a tempting option is
      to evaluate the power of these different statistics prior to make any decision.
      We review the available methods dedicated to power computation and assess their
      respective reliability in treating a wide range of tests on a wide range of
      alternative models. Considering Monte-Carlo, non-central chi-square and Delta
      Method estimates, we evaluate empirical, asymptotic and numerical approaches.
      Additionally we introduce the use of the Delta-Method, extended to order 2,
      intended to provide better results than the traditional order-1 Delta-Method.
      Supplementary data can be found at: http://stat.genopole.cnrs.fr/software/dm2.

PMID- 17032290
TI  - Training in rural practice: time for integration?

PMID- 17032291
TI  - Training doctors in general practices: a review of the literature.
AB  - OBJECTIVE: This study was undertaken to assess the evidence of whether new forms
      of medical training, where substantial training takes place in general practice,
      will be acceptable to GPs. In particular, we asked the questions: Are GPs willing
      to act as trainers and supervisors in their practices? Do GPs have the
      appropriate skills to be trainers? Do practices have the infrastructure and
      resources to support placements? And, are patients happy to be seen by medical
      students and General Practice Registrars? DESIGN: Key Australian and
      international databases, key Australian journals and key Australian websites were
      searched for literature on general practice-based training of medical students
      and General Practice Registrars. RESULTS: In the international and Australian
      literature, we found that many GPs consider training medical students and General
      Practice Registrars to be intrinsically satisfying. They vary in their skills,
      and most medical schools have made significant investments in training and
      support activities. Many practices do not have the necessary infrastructure, and
      investments need to be made if extended placements are to be successful. Many
      patients are happy to be seen by students and Registrars, but careful thought
      needs to be given to implementing appropriate models so that students have good
      learning opportunities, patients are not disadvantaged and general practices can
      operate efficiently. CONCLUSION: The success of this new model of clinical
      placements is dependent on medical schools having a detailed understanding of the
      needs and expectations of GPs.

PMID- 17032292
TI  - Housing and health in Indigenous communities: key issues for housing and health
      improvement in remote Aboriginal and Torres Strait Islander communities.
AB  - Indigenous people living in remote communities face some particular difficulties
      with regard to housing and its impact on their health. This paper reviews the
      contemporary international understanding of the relationship between housing and
      health, the history of settlement and housing conditions in remote Aboriginal and
      Torres Strait Islander communities, and some of the recent initiatives to improve
      housing in these communities.

PMID- 17032293
TI  - Partnerships in specialty care: exploring rural haemophilia provider resource
      needs.
AB  - OBJECTIVE: The purpose of this study was to determine whether rural providers
      have adequate preparation for safe and effective haemophilia care. DESIGN: This
      qualitative study proceeded in two phases: focus group (phase I) and telephone
      (phase II) interviews. SETTING: Five Canadian rural hospitals served by one urban
      haemophilia treatment centre and providing service to at least one haemophilia
      family. PARTICIPANTS: Phase I: focus groups of rural health professionals (site
      1: n = 5; site 2: n = 6), including nursing, medicine and lab technology. Phase
      II: telephone interviews with nine participants from nursing, medicine, lab
      technology, social work and physiotherapy across three sites. MAIN OUTCOME
      MEASURES: Qualitative content analysis yielded categorical themes for specialty
      care resource requirements in a rural context. RESULTS: Resource needs reflected
      five main categories: communication network, subjective knowledge, team roles,
      objective knowledge and partnerships (C-STOP). CONCLUSIONS: The five C-STOP
      categories require resources and alignment of urban specialist, rural provider
      and family expertise. Specialty clinic efforts promoting self-care are incomplete
      without matched resources for rural providers.

PMID- 17032294
TI  - Motorcycle deployment and rider characteristics on Victorian farms.
AB  - OBJECTIVE: To describe the motorcycle fleet and rider characteristics on
      Victorian farms. DESIGN: Cross-sectional postal survey. SETTING: Victorian
      agricultural industries. PARTICIPANTS: A total of 1382 randomly selected farmers
      in 2001. MAIN OUTCOME MEASURES: Farm motorcycle characteristics, use and
      maintenance schedule; motorcycle rider characteristics, respondent demographics
      and property characteristics. RESULTS: A total of 70% of farms had motorcycles,
      with an average of 1.7 per property. A total of 49% were four-wheel, and 44% were
      two-wheel. The average engine size and age were 255 cc and 8.8 years,
      respectively. The milk cattle sector owned the largest share of the motorcycle
      fleet and cereal/grain farms the smallest share. Four-wheel motorcycles were
      often used across the entire spectrum of agricultural tasks. Two-wheel motorcycle
      use was concentrated more on mustering and transport. A total of 61% of farms
      performed motorcycle maintenance every 1-6 months. Fifteen per cent of riders
      were under 15 years of age, and the majority (71%) rode four-wheel motorcycles. A
      total of 29% of all riders had received some form of motorcycle training.
      CONCLUSIONS: This study provides useful information on state-level patterns of
      farm motorcycle use, as well as the key safety behaviours of rider training and
      motorcycle maintenance. This information might serve as baseline data for future
      monitoring and surveillance, and might assist with planning of prevention
      programs.

PMID- 17032295
TI  - Impact of support initiatives on retaining rural general practitioners.
AB  - OBJECTIVE: This study aimed to evaluate the impact of the Dr DOC program, a rural
      doctor workforce support program, which consists of social and psychological
      support and practical interventions, on the well-being and retention of rural
      GPs. DESIGN: Rural GPs were assessed on different aspects of well-being and their
      intentions to leave rural general practice, and these were compared with similar
      data collected two years prior. SETTING: Rural general practices in South
      Australia. PARTICIPANTS: Two hundred and twenty-one rural GPs (55% of South
      Australian rural GP workforce). MAIN OUTCOME MEASURES: GPs completed a
      questionnaire assessing their levels of support, intention to leave rural
      practice, use of the dr doc program, and psychological health. RESULTS:
      Improvements were found in the support networks and in the physical and emotional
      health of rural GPs from time 1 to time 2. There was also a reduction in the
      number of GPs wanting to leave rural general practice in the short to medium term
      (from 30% to 25%). CONCLUSIONS: The initial study in this series suggested that
      improving psychological well-being might influence rural GPs' intentions to leave
      rural practice. The current study confirms these suggestions by demonstrating
      that programs targeted at psychological and physical well-being do indeed impact
      on rural GPs' intentions to leave. The results of this study highlight the role
      of psychological well-being in retaining rural GPs and emphasise the value of
      developing psychologically based programs to not only boost the physical and
      mental health of GPs, but also to reduce departure from rural areas.

PMID- 17032296
TI  - Orientation for general practice in remote Aboriginal communities: a program for
      registrars in the Northern Territory.
AB  - BACKGROUND: Remote general practice can be a highly rewarding career, but poses
      many personal and professional challenges. It is characterised by significant
      geographical, professional and social isolation and a requirement for
      practitioners with public health, emergency and extended clinical skills. The
      remote practitioner faces further challenges in the remote Aboriginal community
      setting, including language and cultural barriers. OBJECTIVES: This paper
      discusses the specific components of a remote Aboriginal community general
      practice registrar orientation program in the Northern Territory, and their
      particular importance and relevance to remote training and practice in this
      context. DISCUSSION: Northern Territory General Practice Education, the regional
      general practice training provider in the Northern Territory, has developed a
      model for a comprehensive orientation program for general practice registrars
      planning to work in remote Aboriginal community locations. This comprises a
      number of core components, including communication and cultural safety training;
      clinical and procedural skill development; population health; self-care and
      personal/professional role delineation; and organisational issues. We believe it
      is a program that is applicable to other disciplines undertaking work in remote
      Aboriginal communities.

PMID- 17032297
TI  - Small-area estimates of general practice workforce shortage in rural and remote
      Western Australia.
AB  - OBJECTIVE: To trial a measure of rural and remote GP access for small areas.
      DESIGN: A cross-sectional study using geographical information systems software
      to calculate GP to population rates with a floating catchment of 100 km radius
      around census collection districts (CCDs). SETTING: Non-metropolitan Western
      Australia. PARTICIPANTS: The locations and full-time equivalents of GPs and other
      primary-care doctors were identified through a GP workforce survey. MAIN OUTCOME
      MEASURES: GP to population ratios for each CCD were classified as being above or
      below a benchmark of adequate GP access. CCDs with no GP sessions reported within
      100 km were identified separately. These categories were investigated by
      divisions of general practice and by indigenous status, age and employment
      characteristics of the population. RESULTS: Small-area estimates detected greater
      variation in access than depicted by conventional methods. Sixty-four per cent of
      the non-metropolitan population live in CCDs with adequate GP access. Forty-five
      per cent of indigenous people and 52% of people working in rural industries live
      in CCDs with access below the benchmark. CONCLUSIONS: The floating catchment
      method is a powerful tool to identify small areas of inadequate service. It can
      be applied to measure access to other professionals, medical equipment or
      facilities.

PMID- 17032298
TI  - Factors affecting the recruitment and retention of pharmacists to practice sites
      in rural and remote areas of New South Wales: a qualitative study.
AB  - OBJECTIVE: To explore factors affecting recruitment and retention of pharmacists
      in rural/remote areas of New South Wales (NSW). DESIGN: Qualitative
      semistructured in-depth interviews. SETTING: Primary care--rural/remote community
      pharmacies. PARTICIPANTS: Purposive sample of 12 community pharmacists. MAIN
      OUTCOME MEASURES: Factors affecting recruitment and retention of pharmacists in
      rural/remote areas of NSW. RESULTS: Respondents reported a variety of personal
      and professional reasons for taking up rural practice, including previous rural
      experience and a preference for working in rural over metropolitan areas. The
      main factor affecting retention in rural areas was the high level of professional
      satisfaction and interprofessional rapport. Perceived reasons for the current
      under-supply of pharmacists to rural/remote areas of NSW included changing
      demographics of the pharmacy undergraduate degree programs and pharmacy
      workforce, and negative perceptions of rural pharmacy practice and rural
      lifestyle. CONCLUSIONS: This study identified factors believed to affect
      recruitment and retention of pharmacists in rural/remote areas. There appears to
      be considerable overlap between the factors, with different weightings of
      importance for different individuals. The lack of consensus for a proposed method
      of resolving this problem highlights its complexity and the need for further
      studies in this area.

PMID- 17032299
TI  - Wagga Wagga specialist outreach palliative medicine service: a report on the
      first 12 months of service.
AB  - OBJECTIVE: This paper reports on and discusses the development of a visiting
      palliative medicine specialist outreach service for Wagga Wagga New South Wales,
      Australia, and presents initial data and three case vignettes for reflection. The
      visiting doctor was flown from Sydney each fortnight for a day and integrated
      with the local nursing based palliative care team. METHODS: Demographic data was
      collected over the initial 12 months of service, which included the location of
      the consult (hospital, home, nursing home), whom the consult was from
      (specialist, GP), age of the patient, location of death, type of cancer, as well
      as the complexity of consultation from the perspective of one of the authors.
      RESULTS: The majority of referrals were for advice on cancer pain control (62.3%)
      and other symptoms (26.7%) confirming the expectation. Those patients referred
      were considered appropriate, with over 75% having a palliative care issue that
      was considered appropriate for direct patient contact by the specialist in
      palliative medicine. CONCLUSIONS: The provision of a visiting palliative medicine
      specialist to rural areas has been developed over the last few years in New South
      Wales and the reporting of the success of this particular service aims to provide
      evidence for the need and the development of further services, as it is expected
      that this service would continue but with an increasing number of referrals as
      the service became increasingly known.

PMID- 17032300
TI  - Preparing professionals from a wide range of disciplines for life and work in
      rural and small communities.
AB  - A new inter-professional subject has been offered at a Canadian university, which
      examines issues related to professionals' integrating into rural practice;
      understanding the history and geography of rural communities and important issues
      affecting life in rural settings.

PMID- 17032301
TI  - Rural women's referral journeys after myocardial infarction.

PMID- 17032302
TI  - Career preferences of new medical students at four Australian universities: rural
      family medicine versus the rest.

PMID- 17032303
TI  - Limited wrist arthrodesis.

PMID- 17032304
TI  - Walking the void: being a rural PhD candidate.

PMID- 17032305
TI  - Managing staff turnover: orientation packs.

PMID- 17032308
TI  - SARRAH: Looming crisis in undergraduate allied health professional clinical
      placements.

PMID- 17032310
TI  - Anti-tumor effect in an in vivo model by human-derived pancreatic RNase with
      basic fibroblast growth factor insertional fusion protein through antiangiogenic
      properties.
AB  - It is thought that the export of angiogenic fibroblast growth factors (FGF) from
      tumors may be involved in the onset of tumor angiogenesis. To create a new active
      targeting drug that inhibits the tumor angiogenic process without toxicities to
      normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89
      position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding
      site of cross-linked human pancreatic RNase) to prevent stereospecific binding to
      RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF
      and as RNase1. Furthermore, it acquired an additional ability of evading RI
      through steric blockade of RI binding caused by the fused h-bFGF domain. In the
      present study, the effect of the resultant protein, CL-RFN89, on the antitumor
      response though its antiangiogenic properties was investigated in an in vivo
      model. Continuous systemic treatment with CL-RFN89 significantly inhibited the
      growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment
      with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with
      control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat
      antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor
      vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor
      of tumor growth as a result of its antiangiogenic properties. This protein
      appears to be a new systemic antitumor agent.

PMID- 17032311
TI  - Inhibitory effect of c-Met mutants on the formation of branching tubules by a
      porcine aortic endothelial cell line.
AB  - The association of hepatocyte growth factor (HGF) with its high-affinity receptor
      (c-Met) has been shown to induce mitogenesis, motogenesis and morphogenesis in a
      variety of cell types. Various point mutations in c-Met have been identified in
      hereditary and sporadic papillary renal carcinomas as well as in other
      carcinomas. In the present study, we examined the effects of c-Met point
      mutations on the morphology of a porcine aortic endothelial (PAE) cell line. When
      cultured in three-dimensional collagen gel, PAE cells formed branching tubule
      structures, and HGF treatment caused breakdown of the structures and induced a
      scattered morphology. The exogenous expression of c-Met point mutants inhibited
      the formation of tubules. HGF treatment induced the formation of tubules by PAE
      cells expressing some c-Met mutants, but it induced the scattering of PAE cells
      expressing other c-Met mutants. The presence of a low concentration of a mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase (MEK)
      inhibitor cancelled the inhibitory effect of the c-Met point mutations on the
      formation of tubules. These results suggest that c-Met point mutations affect the
      extracellular signal-regulated kinase (ERK) signaling required for the formation
      of tubules by PAE cells, and HGF binding changes the conformation of c-Met
      mutants, leading to the different signals required for formation of tubules and
      cell scattering.

PMID- 17032312
TI  - Genetic instability on chromosome 17 in the epithelium of non-polypoid colorectal
      carcinomas compared to polypoid lesions.
AB  - Early colorectal carcinomas (submucosal invasive adenocarcinomas) can be
      classified into polypoid growth carcinoma (PG-Ca) and non-polypoid growth
      carcinoma (NPG-Ca) types, the latter transforming more rapidly to advanced
      carcinoma. Previously, we indicated that stromal genetic instability might
      contribute to tumorigenesis of both sporadic and ulcerative colitis-associated
      colorectal adenocarcinomas. In the present study, we analyzed genetic instability
      of both epithelial and surrounding stromal components in PG-Ca and NPG-Ca. In 99
      colorectal submucosal invasive adenocarcinomas, epithelial and stromal genetic
      instability was analyzed with National Cancer Institute standard microsatellite
      markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related
      markers, using a combination of the laser-captured microdissection and GeneScan
      approaches. Immunohistochemical analysis was carried out for hMLH1, hMSH2, MGMT
      and p53. In addition, we investigated methylation of the hMLH1 and MGMT
      promoters. The frequencies of epithelial microsatellite instability (MSI) with
      Chr.17 markers were significantly higher in NPG-Ca (33.3%) compared to PG-Ca
      (10.4%), particularly with D17S579 and D17S796. For loss of heterozygosity, only
      D17S786 showed a significant difference. The frequencies of stromal MSI with all
      markers were 31.7% and 25.9% in NPG-Ca and PG-Ca, respectively, but D17S579 and
      TP53 showed higher MSI in NPG-Ca than PG-Ca. Immunohistochemically, p53 protein
      expression in PG-Ca was significantly higher in loss of heterozygosity-positive
      cases with altered Chr.17 markers overall, especially the D17S796 marker,
      compared to cases without genetic instability. These results suggest that
      epithelial and stromal MSI of Chr.17 markers contributes more to carcinogenesis
      in NPG-Ca, whereas stromal genetic instability might be necessary for the
      development of both types of colorectal carcinoma.

PMID- 17032313
TI  - Therapeutic targeting of the endothelin a receptor in human nasopharyngeal
      carcinoma.
AB  - The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many
      malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET(A)R
      expression is an independent determinant of survival and a robust independent
      predictor of distant metastasis. To evaluate whether ET(A)R represents a new
      target in NPC treatment, we tested the therapeutic role of ET(A)R in NPC. Cell
      proliferation was inhibited by the ET(A)R-selective antagonist ABT-627 in two
      ET(A)R-positive NPC cells in a dose-dependent manner. Proliferation of ET(A)R
      negative NPC cells was not decreased. ET(A)R blockade also resulted in
      sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice,
      ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT
      627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive
      antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on
      an experimental lung metastasis by a reduction in the number of tumors. These
      results support the rationale of combining ABT-627 with current standard
      chemotherapy to further improve the therapeutic ratio in the treatment of NPC.

PMID- 17032315
TI  - Er:YAG laser resurfacing for inoperable medium-sized facial congenital
      melanocytic naevi in children.
AB  - Congenital melanocytic naevi (CMN) can cause significant psychosocial morbidity,
      especially if they are in visually exposed areas. The preferred treatment is
      surgical excision, though not all lesions are amenable to this because anatomical
      location may preclude aesthetic and functional reconstruction. Three children
      with inoperable facial CMN were treated with Er:YAG resurfacing under general
      anaesthetic. Two children were Fitzpatrick skin type II, and one child was skin
      type VI. Treatment was performed at 4-9-monthly intervals. The procedure achieved
      significant lightening and thinning in all three cases, without scarring or
      dyspigmentation. One child developed herpes simplex infection in the treated area
      on one occasion, which was managed with oral aciclovir, and did not lead to
      scarring or preclude further treatment. We conclude that Er:YAG laser resurfacing
      is effective for CMN, even in darker skin types. The incidence of side-effects is
      low, although repeated treatment is necessary.

PMID- 17032316
TI  - Effects of oral isotretinoin therapy on peripheral nerve functions: a preliminary
      study.
AB  - Accumulating evidence over the past decade indicates that synthetic retinoids may
      be capable of affecting both growth and differentiation of nervous tissue. Our
      aim was to substantiate possible side-effects of oral isotretinoin therapy on
      peripheral nerve functions, both neurologically and neurophysiologically. We
      performed neurological examination and electroneuromyographic studies on 18
      patients with various skin diseases before, at the third month, and at the end of
      isotretinoin treatment. Abnormal neurophysiological findings in this study point
      towards a typical distal, length-dependent and predominantly sensory
      polyneuropathy. Clinicians should be aware of possible neurological sensorial
      symptoms during isotretinoin therapy. In our opinion, electroneuromyographic
      investigation should be performed on all patients reporting symptoms (e.g.
      paresthesia, numbness, sensory loss) before and during oral isotretinoin
      treatment. The precise clinical significance of the isotretinoin-induced
      neurophysiological alterations reported here remains to be determined in further
      studies.

PMID- 17032317
TI  - Transanal endoscopic microsurgery: the preferred technique in a small but
      important group of rectal neoplasms.

PMID- 17032318
TI  - Surgery for local recurrence of rectal cancer.
AB  - OBJECTIVE: Despite improvement in management of primary rectal cancer, 2.6-32% of
      patients develop local recurrence. A proportion of these patients can be amenable
      to salvage surgery. The present article reviews the evidence for and against the
      surgical management for local recurrence of rectal cancer, the role of adjuvant
      and intraoperative radiotherapy (IORT), and evaluates short and long-term
      outcomes. METHOD: A literature search was performed using Medline, Embase, Ovid
      and Cochrane database for studies between 1980 and 2005 assessing surgical
      management of local recurrence of rectal cancer and the evidence was critically
      evaluated. RESULTS: Nearly 50% of rectal cancer recurrences are local and are
      therefore potentially amenable to curative resection. Preoperative imaging is
      important for appropriate selection of patients for surgery and preoperative
      adjuvant therapy is essential. Five-year survival following resection ranges from
      18% to 58% with 5-year survival following complete resection of over 35% though
      morbidity ranges from 21% to 82%. Neoadjuvant radiotherapy is beneficial and IORT
      may have a contributory role in treatment. Aggressive surgical treatment
      favourably affects quality of life and is cost effective. Surgery for local
      recurrence can result in significant long-term survival with acceptable morbidity
      and improved quality of life in appropriately selected patients. Assessment in a
      specialist centre familiar with these techniques is essential.

PMID- 17032319
TI  - Life-threatening sepsis following treatment for haemorrhoids: a systematic
      review.
AB  - INTRODUCTION: Haemorrhoids are a common complaint with estimates suggesting a
      prevalence of 4% of the adult population. Treatments such as rubber band ligation
      (RBL), sclerotherapy and excisional surgery have been in use for many years, and
      recently stapled haemorrhoidopexy, or procedure for prolapsing haemorrhoids (PPH)
      has gained acceptance. However, there have been consistent reports of severe
      sepsis, including a number of deaths. The purpose of this review was to assess
      the scale of the problem, and identify any predisposing factors, common
      presenting features, and treatment options in those who suffer these
      complications. RESULTS: Twenty-nine papers were identified, reporting 38
      patients. Of these, 17 had undergone RBL, three had sclerotherapy, one had
      cryotherapy, 10 had excisional surgery and seven had PPH. Ten died as a result of
      their sepsis. The cases included 16 with perineal sepsis, seven with
      retroperitoneal gas and oedema, and six with liver abscesses. Common presenting
      features were urinary difficulties, fever, severe pain, septic shock and
      leucocytosis. Most were managed by means of surgery, although a minority survived
      having received conservative therapy. With the exception of two patients (one of
      whom was human immunodeficiency virus positive and the other had a drug-induced
      agranulocytosis) all were well prior to surgery. CONCLUSIONS: Although extremely
      uncommon, severe sepsis does occur post-treatment for haemorrhoids and all
      surgeons who treat such patients should be aware of the potential complications
      and alert to their presenting features. Early presentation without evidence of
      tissue necrosis may be managed conservatively, although most cases are managed by
      means of surgery.

PMID- 17032320
TI  - Short course preoperative radiotherapy is the single most important risk factor
      for perineal wound complications after abdominoperineal excision of the rectum.
AB  - AIM: To determine factors associated with perineal wound complications following
      abdominoperineal excision of the rectum (APER) for rectal adenocarcinoma and
      their effects on time to healing. PATIENTS AND METHODS: We studied all cases of
      APER performed in our unit by four consultants over 7 years. Seven out of nine
      factors considered important in wound healing were analysed using logistic
      regression and a multivariate model was built to examine interactions. Wound
      persistence was calculated using the Kaplan-Meier method. RESULTS: Data were
      available for 94 of 96 patients [male:female, 3:2, median age 72.5 (IQR: 64-78)].
      Thirty-nine (41%) patients had 25 Gray, 3-portal, fractionated 5-day short course
      preoperative radiotherapy (SCPRT). Dukes stages were A (34%), B (26%), C (40%).
      Perineal wound complications occurred in 44 (47%), 16% of these requiring return
      to theatre. Local recurrences occurred in 13 (15%). There was no evidence to
      suggest that either patient gender, age, smoking status, preoperative albumin or
      haemoglobin level, or T stage were associated with the development of wound
      complications. The odds of wound complications for a patient who had SCPRT was
      over 10 times that for a patient who did not have preoperative radiotherapy (odds
      ratio 10.15, 95% CI: 3.80-27.05, n = 94). Seventy-four per cent of SCPRT and 96%
      of non-SCPRT wounds had healed by 1 year. Estimated failed wound healing rates at
      30 and 90 days were 64% (95% CI: 46-78) and 48% (95% CI: 30-64) in SCPRT patients
      compared with 23% (95% CI: 12-35) and 9% (95% CI: 3-20) in non-SCPRT patients
      (log rank test P < 0.0001). CONCLUSION: Patients who have an APER are over 10
      times more likely to have a perineal wound complication if they have SCPRT than
      not. Two-thirds of these will not have healed by 1 month, half by 3 months and
      over a quarter will still remain unhealed at 1 year. This has important
      implications for patient management decisions. Large prospective studies are
      needed to evaluate the effects of a selective policy for radiotherapy
      administered to patients requiring APER.

PMID- 17032321
TI  - Long-term results of surgically treated traumatic rectourethral fistulas.
AB  - OBJECTIVE: Rectourethral fistulas are uncommon, usually iatrogenic injuries that
      are demanding to treat. We present the challenging problems involving the
      treatment of rectourethral fistulas caused by war wounds. MATERIALS AND METHODS:
      In the period 1991-1996, during the war in Croatia and Bosnia, six patients with
      rectourethral fistulas caused by war injuries were operated in our institution by
      the same surgeon. All patients were young males with a mean age of 24.6 years. In
      all patients, double diversion (diversion colostomy and cystostomy) was performed
      at the time of the injury in military hospitals. In three patients, multiple
      unsuccessful operations were performed in other institutions to close
      rectourethral fistula. We found urethrocystography and proctoscopy as the most
      reliable diagnostic studies and performed them in all patients. In first three
      patients, we performed transanal repair with anterior rectal wall advancement
      flap. Because it failed in all three patients, we performed York-Mason trans
      sphincteric approach and anterior rectal wall advancement flap after which
      rectourethral fistula closed in all patients. Because of the satisfactory
      results, we performed the same procedure in other three patients. RESULTS: In all
      patients rectourethral fistula healed 2 months after the operation. Closure of
      diverting colostomy was performed after urethrocystography and proctoscopy proved
      that the rectourethral fistula has healed. There were no operative deaths and no
      major complications. Urethral stenosis developed in one patient and was
      successfully managed by dilatation. CONCLUSION: We believe that York-Mason trans
      sphincteric approach offers straightforward access through healthy tissues and
      good fistula visualization. Anterior rectal wall advancement flap can easily be
      performed and offer good chances for definitive closure of the rectourethral
      fistula.

PMID- 17032322
TI  - A single common urgent pathway for all colorectal referrals reduces time to
      diagnosis and treatment.
AB  - OBJECTIVE: Guidelines for the urgent referral of patients with suspected
      colorectal cancer were introduced in 2000. They aimed to facilitate the prompt
      diagnosis and treatment of patients with symptoms suggestive of malignant
      disease. Recent assessment of these guidelines has suggested that although they
      identify 9-14% of patients with colorectal cancer, they may be used
      inappropriately and may lead to delays in treatment for those patients with
      cancers whose symptoms do not fit the guidelines. We aimed to assess the effect
      of introducing a single pathway for all referrals irrespective of indicated
      urgency. METHOD: All referral letters to a single consultant colorectal surgeon
      over a 6-month period were coded 'urgent' irrespective of the indicated urgency
      on the original referral letter. Data was collected prospectively on 47 patients
      diagnosed with colorectal cancer identified over the trial period. Patient
      demographics, the mode of presentation, urgency of referral and waiting times
      were documented. RESULTS: Following the introduction of the common urgent
      referral pathway, no patient waited longer than 62 days from referral to
      treatment or 31 days from the decision to treat to first treatment, thus meeting
      government targets introduced in 2005. CONCLUSION: The introduction of the urgent
      referral guidelines has accelerated the referral pathway for patients with
      symptoms suggestive of colorectal cancer, although this is at the expense of the
      majority of patients who present via conventional pathways. The introduction of a
      common urgent pathway allows prompt diagnosis and treatment and is of particular
      benefit for the majority of patients not referred via the 2-week standard. Until
      a more accurate method of identifying the highest risk patients is implemented,
      we suggest that all patients are seen on an urgent basis.

PMID- 17032323
TI  - Magnetic resonance imaging pelvimetry in 186 patients with rectal cancer confirms
      an overlap in pelvic size between males and females.
AB  - INTRODUCTION: It has generally been considered that open pelvic surgery is almost
      always easier in female subjects because of anatomical differences facilitating
      surgical access. In contrast, the male pelvis has been considered to be narrower
      and deeper. The objective of this study was to assess magnetic resonance imaging
      (MRI) pelvimetry in patients with rectal cancer in whom any difference in
      pelvimetry may potentially affect operative management. Male and female pelvic
      bony dimensions were compared. METHOD: A cohort of 186 patients (112 males and 74
      females) with rectal cancer who had been recruited prospectively to the Magnetic
      Resonance Imaging and Rectal Cancer European Equivalence Study (MERCURY Study)
      were assessed. Complete digital images were available on these patients. A
      comparison of the pelvic dimensions was made between the sexes using 16
      dimensions measured on the MRI workstation using the mid-sagittal and axial
      images. RESULTS: There was no significant difference and considerable overlap
      between the sexes with respect to each of the 14 parameters measured from the
      preoperative sagittal MRI scan. However, there was a highly significant
      difference between the interspinous and intertuberous transverse diameter of the
      pelvis (P < 0.0001). CONCLUSION: Outcome after surgery may be influenced by the
      technical difficulty of the operation and this had been thought to be partly
      affected by the pelvic size. In this cohort of 186 patients, the only difference
      seen between the sexes, was in the transverse mid-inlet and pelvic outlet
      diameter.

PMID- 17032324
TI  - Management of intersphincteric abscesses.
AB  - OBJECTIVE: Intersphincteric abscesses are relatively rare, and in some cases of
      upward extensions in the supralevator plane, can be difficult to manage. The aim
      of this study was to analyse the type of treatment used in these abscesses.
      METHODS: Twenty-one intersphincteric abscesses treated by endoanal drainage in
      our colorectal unit between 1992 and 2004 were reviewed from our database;
      location and extension of the abscess, type of treatment and recurrence rates and
      the use of endoanal ultrasound were studied. RESULTS: Ninety per cent of patients
      were male; 10 had a previous history of surgery for perianal abscess and
      suppuration (48%); 16 (76%) had a posterior location and five were anterolateral.
      Twelve patients had low intersphincteric abscesses and were treated by laying
      open the abscess and dividing the internal sphincter. Nine were found to have
      high extensions into the intermuscular planes and were treated by staged
      procedures: a temporary transanal mushroom catheter was used in seven patients.
      Endoanal ultrasound was used initially in seven patients (33.3%) and for the
      evaluation of definitive treatment in 11 (52%). CONCLUSIONS: Low intersphincteric
      abscesses should be treated by de-roofing of the abscess and division of the
      internal sphincter up to a level of the dentate line. High intersphincteric
      abscesses are relatively frequent and mostly require staged surgery with a
      temporary mushroom (de Pezzer) catheter. Accurate anatomical ultrasound
      localization and proper drainage become important to avoid recurrences or
      extrasphincteric fistulas.

PMID- 17032325
TI  - Anxieties should not be forgotten when screening relatives of colorectal cancer
      patients by colonoscopy.
AB  - OBJECTIVE: Individuals with a strong family history have a high risk of
      developing colorectal cancer. They could well benefit from targeted screening and
      their increased risk warrants an invasive procedure such as colonoscopy. This
      study aims to assess the anxieties of symptom-free relatives offered screening by
      colonoscopy. METHOD: A simple questionnaire was sent to 50 consecutive people who
      had colorectal cancer screening by colonoscopy because of a strong family
      history. RESULTS: Forty-five questionnaires were answered. On assessing their
      anxiety levels before and after colonoscopy, 56% noticed an improvement after the
      test, 33% were still as anxious and 11% had raised anxiety levels despite
      screening. Although most of the screening colonoscopies were normal, 44% of
      asymptomatic relatives undergoing invasive screening had no improvement of their
      cancer anxieties. CONCLUSION: Screening people with a strong family history of
      colorectal cancer may be an efficient, cost-effective and focussed way of
      detecting early neoplasms rather than screening the general population. Using
      colonoscopy alone however, a large proportion of people still have cancer
      anxieties after being screened. This small study suggests that in order to
      attempt to alleviate anxieties, a colonoscopy alone is insufficient for some in
      this high-risk group.

PMID- 17032326
TI  - A prospective evaluation of occult disorders in obstructed defecation using the
      'iceberg diagram'.
AB  - OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD)
      carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by
      'underwater rocks' or occult diseases which may affect the outcome of surgery.
      The aim of this study was to evaluate occult disorders in order to alert the
      clinician of these and minimize failures. METHOD: One hundred consecutive
      constipated patients with OD symptoms, 81 female patients, median age 52 years,
      underwent perineal examination, proctoscopy, anorectal manometry, and
      anal/vaginal ultrasound. Anorectal physiology and imaging tests were also carried
      out when indicated, as well as psychological and urogynaecological consultation.
      Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g.
      rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using
      a novel 'iceberg diagram'. The type of treatment, whether conservative or
      surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal
      prolapse and rectocele. All patients had at least two occult OD-related diseases,
      66 patients had at least three: anxiety-depression, anismus and rectal
      hyposensation were the most frequent (66%, 44% and 33% respectively). The median
      constipation score was 11 (range 2-20), the median number of 'occult disorders'
      was 5 (range 2-8). Conservative treatment was carried out in most patients.
      Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg
      diagram' allowed the adequate evaluation of OD-related occult diseases and better
      selection of patients for treatment. Most were managed conservatively, and only a
      minority were treated by surgery.

PMID- 17032327
TI  - Do supervised colorectal trainees differ from consultants in terms of quality of
      TME surgery?
AB  - OBJECTIVE: The quality of surgical excision is held to be a major determinant of
      outcome following surgery for rectal cancer. Macroscopic examination of the
      excised mesorectum allows for reproducible assessment of the quality of surgery.
      We aimed to determine whether quality of excision undertaken by colorectal
      trainees under supervision was comparable with that performed by consultants, as
      measured using mesorectal grades. METHOD: A total of 130 consecutive patients
      undergoing potentially curative resection for primary adenocarcinoma of the
      rectum in our centre from 2001 to 2003 were included in the study. The
      pathologists graded the excised mesorectum according to staged classification
      proposed by Quirke. The outcome (quality of mesorectal excision and secondary
      outcomes including local recurrence and overall recurrence) of operations
      performed by consultants was compared with that of trainees. Statistical
      significance was tested using Pearson chi(2) test. RESULTS: Eighty-nine
      operations were performed by consultants and 41 by senior colorectal trainees
      with consultant supervision. Forty-four patients (49%) had good mesorectum when
      operated by consultants in comparison with 17 (41.5%) by the trainees. There was
      no statistically significant difference (P = 0.717) between the two groups in
      terms of quality of mesorectum excised after potentially curative resection.
      Furthermore, there were seven local recurrences in patients operated by
      consultants (7.8%) when compared with four in the trainee group (9.5%) and once
      again there was no statistical significance between the two groups (P = 0.719).
      CONCLUSION: We conclude that the quality of rectal cancer excision, as defined by
      mesorectal grades, achieved by supervised colorectal trainees is comparable with
      that achieved by consultants.

PMID- 17032328
TI  - Transanal endoscopic microsurgery: risk factors for local recurrence of benign
      rectal adenomas.
AB  - OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a minimally invasive
      technique for excision of selected benign and malignant rectal neoplasms. It is
      considered a safe and effective treatment but recurrence rates of 1-13% are
      reported for benign lesions. The aim of this study was to assess risk factors for
      local recurrence of benign rectal lesions and to evaluate mortality and morbidity
      following TEM. METHOD: Data were prospectively collected from all patients
      undergoing TEM for benign adenomas from January 1998 to March 2005. The procedure
      was performed by a single surgeon and patients were regularly followed up.
      RESULTS: One hundred and forty-six procedures were included, with a median
      patient age of 74 years (range 22-92 years). The mean lesion area was 16 cm(2)
      (range 0.3-150 cm(2)) and the median distance from the dentate line was 9 cm
      (range 0-17 cm). Immediate complications included bleeding (six) and acute
      urinary retention (six). There has been one (0.68%) procedure-related death.
      After a median follow up of 39 months (range 4-89 months) there have been seven
      recurrences (4.8%), recurring at a mean time of 23.3 months (range 5-48 months).
      Only microscopic involvement of the circumferential resection margin was found to
      be significantly associated with recurrence (P = 0.0059). Recurrence was not
      associated with age, size of lesion, previous treatment, severity of dysplasia or
      use of the harmonic scalpel. CONCLUSION: TEM is a safe and effective treatment
      for benign rectal adenomas. Circumferential resection margin involvement is
      associated with recurrence, which tends to occur late. Therefore extended follow
      up is recommended.

PMID- 17032329
TI  - The clinical significance of the circumferential resection margin following
      preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common
      language.
AB  - OBJECTIVE: The presence of microscopic tumour cells within 1 mm of the
      circumferential surgical resection margin (CRM) is the endpoint most strongly
      associated with local recurrence in rectal cancer and doubles the risk of
      developing distant metastases. Reporting on the CRM can monitor surgical quality
      assurance and over the past two decades has driven advances in surgical technique
      with the increasing use of total mesorectal excision. The aim of this review was
      to use the evidence from both phase II and phase III randomized trials of
      preoperative radiotherapy and chemoradiation in rectal cancer, to assess how
      often CRM involvement is currently documented and examine its utility as an early
      predictor of both disease-free and overall survival. METHOD: A literature search
      identified both randomized and nonrandomized trials of preoperative radiation
      therapy and chemoradiation therapy in rectal cancer since 1993. The aim was to
      find those studies, which documented the distance from the periphery of the
      tumour and the CRM. Small trials treating < 20 patients were excluded. RESULTS:
      One hundred and eighty-seven phase II and 28 phase III trials of preoperative
      radiotherapy or chemoradiation were identified. Most trials documented the degree
      of response but only 10 of 187 phase II/retrospective studies and four of 28
      phase III trials presented data on the achievement of a negative CRM. Few defined
      this early pathological endpoint prospectively with accurate measurements.
      However, the majority of studies did use the definition of <or= 1 mm as an
      involved CRM. Discussion Pathological parameters have been used as early
      endpoints to compare studies of preoperative radiotherapy or chemoradiation. It
      remains uncertain whether the degree of response to chemoradiation (e.g. complete
      pathological response, downsizing the primary tumour, sterilizing the regional
      nodes, tumour regression grades or residual cell density) or the achievement of a
      curative resection (uninvolved CRM) is the best early clinical endpoint.
      Retrospective studies in rectal cancer have confirmed a strong association
      between the presence of microscopic tumour cells within 1 mm of the CRM and
      increased risks of both local recurrence and distant metastases. However, as yet
      this early pathological endpoint lacks structured measurement and analysis
      techniques to control for intra- and inter-observer variation and has not been
      validated as a potential surrogate for local control and survival.
      Recommendations are made as to the most appropriate information, which should be
      documented in future trials. CONCLUSION: The CRM status predicts outcome after
      surgery alone, preoperative radiotherapy and preoperative chemoradiation. Yet CRM
      status and its measurement has been poorly documented in the literature, and
      rarely as a prospective measure of outcome. The CRM should be measured and
      documented in all cases, using the definition of <or= 1 mm to denote an involved
      CRM. This definition should also be incorporated into future rectal cancer
      studies with the use of a standardized proforma.

PMID- 17032330
TI  - The rectal pocket syndrome after stapled mucosectomy.
AB  - OBJECTIVE: Stapled rectal mucosectomy (SM) is less painful than manual
      haemorrhoidectomy but may be followed by unusual complications which may require
      reinterventions. The aim of the present study was to report on a particular
      postoperative complication, the rectal pocket syndrome (RPS). METHODS: Six
      patients, four females and two males, five with severe proctalgia and signs of
      intermittent sepsis and one with faecal soiling following SM, underwent clinical
      examination, proctoscopy (n = 5) anal manometry and ultrasound (n = 4) revealing
      a painful rectal intramucosal pocket with an endoluminal orifice at the level of
      the suture line. Four of them underwent a reintervention. RESULTS: At surgery, a
      faecolyth was found to be entrapped in the rectal pocket with an underlying
      chronic abscess in four patients. The cavity was laid open and curetted in all
      cases. One of the females needed a fistulotomy of a low intersphincteric track
      after one year. In none of the others did endorectal pocketing and abscess or
      prostatitis recur after a mean follow up of 25 months (range 2-60 months). The
      male patient still had moderate postevacuation pain and prostatitis possibly via
      a bacterial translocation after two months. Overall, the incidence of the post
      mucosectomy RPS at our Units was 2.5%. CONCLUSIONS: The RPS can occur after SM,
      is likely to be due to a failure of either the purse-string or of the staples
      causing a suture defect leading to an intramural sinus, and may be successfully
      treated by a transanal lay-open in most cases.

PMID- 17032331
TI  - Diverticula of the appendix.

PMID- 17032332
TI  - Metachronous colorectal cancer and age.

PMID- 17032342
TI  - Protein biomarkers associated with acute renal failure and chronic kidney
      disease.
AB  - Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently
      categorized according to serum creatinine concentrations. Serum creatinine,
      however, has shortcomings because of its low predictive values. The need for
      novel markers for the early diagnosis and prognosis of renal diseases is
      imminent, particularly for markers reflecting intrinsic organ injury in stages
      when glomerular filtration is not impaired. This review summarizes protein
      markers discussed in the context of ARF as well as CKD, and provides an overview
      on currently available discovery results following 'omics' techniques. The
      identified set of candidate marker proteins is discussed in their cellular and
      functional context. The systematic review of proteomics and genomics studies
      revealed 56 genes to be associated with acute or chronic kidney disease. Context
      analysis, i.e. correlation of biological processes and molecular functions of
      reported kidney markers, revealed that 15 genes on the candidate list were
      assigned to the most significant ontology groups: immunity and defence. Other
      significantly enriched groups were cell communication (14 genes), signal
      transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein
      markers, nine proteins were also identified by gene expression studies. Next
      generation candidate marker proteins with improved diagnostic and prognostic
      values for kidney diseases will be derived from whole genome scans and protemics
      approaches. Prospective validation still remains elusive for all proposed
      candidates.

PMID- 17032343
TI  - Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and
      oxidized LDL in patients with coronary artery disease.
AB  - BACKGROUND: Remnant lipoprotein particles (RLPs) and oxidative stress are
      components of postprandial state. We investigated the concentrations of
      triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size,
      and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether
      changes among these variables could be associated with the severity and extent of
      coronary artery disease (CAD). MATERIALS AND METHODS: Eighty men and 27 women
      with clinically suspected CAD underwent quantitative coronary angiography (QCA).
      TRLs were isolated by density gradient ultracentrifugation before and 6 h after
      an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by
      ELISA, and LDL size by gradient gel electrophoresis. RESULTS: Triglycerides,
      apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units
      (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h.
      Postprandial cholesterol content of RLPs (RLP-C) correlated with respective
      triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf >
      400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and
      Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed
      state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = 
      0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated
      postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of
      severity and extent of CAD. CONCLUSION: Postprandial state is associated with
      oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and
      is associated with coronary atherosclerosis.

PMID- 17032344
TI  - Copeptin, a fragment of the vasopressin precursor, as a novel predictor of
      outcome in heart failure.
AB  - BACKGROUND: Natriuretic peptides, particularly brain natriuretic peptide (BNP),
      are elevated in heart failure and therefore considered to be excellent predictors
      of outcome. Vasopressin is also known to be related to the severity of heart
      disease. Copeptin--an inactive fragment of the vasopressin precursor--has not
      been previously investigated in the context of heart failure. MATERIALS AND
      METHODS: We prospectively studied 268 patients with advanced heart failure after
      they had been discharged from the hospital. We investigated the ability of BNP
      and copeptin to predict death, re-hospitalization due to heart failure, and a
      combination of the two endpoints. RESULTS: Over a mean follow-up period of 15.8
      months (up to 24 months), 83 patients died, 122 patients experienced worsening of
      heart failure, and 145 patients achieved the combined endpoint. Univariate
      predictors of death were copeptin, BNP, age and impaired kidney function. In
      multivariate analysis, copeptin (chi(2) = 16, P < 0.0001) and age (chi(2) = 4, P
      < 0.05) were independent predictors. Univariate predictors of re-hospitalization
      due to heart failure were copeptin, BNP, age and impaired kidney function.
      Furthermore, in multivariate analysis BNP (chi(2) = 18, P < 0.0001), age (chi(2)
      = 11.8, P < 0.001) and copeptin (chi(2) = 4.2, P < 0.05) were found to be
      independent predictors. CONCLUSION: Our study is the first to show that copeptin
      is an excellent predictor of outcome in advanced heart failure patients. Its
      value is superior to that of BNP in predicting death and a combined endpoint,
      although BNP is still suitable for predicting chronic heart failure (CHF) re
      hospitalization. Our data imply that vasopressin antagonism might be a new target
      to improve outcome in this population.

PMID- 17032345
TI  - Paraoxonase and arylesterase activities in coronary artery disease.
AB  - BACKGROUND: Paraoxonase-1 is an enzyme with three activities which are inversely
      related to cardiovascular diseases. Accordingly, the aim of the study was to
      investigate the paraoxonase, arylesterase activities and oxidative/anti-oxidative
      status in coronary artery disease (CAD) and their correlation with the extent of
      CAD. MATERIALS AND METHODS: Study populations of 193 patients with
      angiographically documented CAD, 83 patients with normal coronary angiograms
      (NCAD) and 55 healthy volunteers were included in the study. The patients with
      CAD were divided into three categories according to the number of diseased
      coronaries. Also, a Gensini score was calculated for each patient. Serum
      paraoxonase and arylesterase activities were measured spectrophotometrically.
      Oxidative and anti-oxidative status was evaluated by measuring serum lipid
      hydroperoxide (LOOH), total anti-oxidant status (TAS) and free sulfhydryl groups
      (-SH = total thiol). Lipid parameters were determined by routine laboratory
      methods. RESULTS: Serum paraoxonase and arylesterase activities, TAS and -SH
      levels were lower in the CAD group compared with the NCAD group and control group
      (P < 0.05, all). Serum LOOH levels of the CAD group were greater than those in
      both the control and NCAD groups (P < 0.05). The major decreases in paraoxonase,
      arylesterase activities, -SH and TAS levels and the major increase in LOOH levels
      were observed in the 3-vessels disease group. In multiple linear regression
      analysis, the Gensini score was independently correlated with paraoxonase
      activity (beta = -0.469, P < 0.001), -SH levels (beta = -0.232, P < 0.001), HDL
      levels and history of diabetes. CONCLUSIONS: Both paraoxonase activity and -SH
      levels are independently associated with the presence and extent of CAD. Reduced
      paraoxonase activity and -SH levels may play a role in the severity of coronary
      atherosclerosis.

PMID- 17032346
TI  - Hypercholesterolaemia alters the responses of the plasma lipid profile and
      inflammatory markers to supplementation of the diet with n-3 polyunsaturated
      fatty acids from fish oil.
AB  - BACKGROUND: The influence of supplementing the diet with long-chain n-3
      polyunsaturated fatty acids (PUFA) from fish oil on plasma lipids and lipid
      peroxides and the production of pro-inflammatory mediators in normolipidaemic and
      hypercholesterolaemic rats were studied. MATERIALS AND METHODS: Rats were divided
      into four groups and fed one of the following diets: a control diet (containing
      4% corn oil); an n-3 PUFA diet [containing 4% eicospentaenoic (EPA) +
      docosahexaenoic (DHA)]; a hypercholesterolaemic diet (HCH); or a HCH + n-3 PUFA
      diet over a 4-week period. Plasma lipids, lipid peroxides, cytokines [tumour
      necrosis factor (TNF)alpha, interleukin (IL)-6, interferon (IFN)gamma] and mRNA
      for hepatic nuclear factor-4alpha (HNF4alpha) were determined. RESULTS: Plasma
      triglyceride (TG), but not cholesterol, levels were decreased by the n-3 PUFA as
      compared with the control diet (P < 0.001), but the addition of n-3 PUFA to the
      HCH diet decreased both the TG (P < 0.01) and cholesterol (P < 0.05)
      concentrations. Plasma lipid peroxides and expression HNF4alpha mRNA were
      increased by n-3 PUFA in the normolipidaemic (P < 0.05), but not in the
      hyperlipidaemic rats. Compared with the control diet group, plasma concentrations
      of TNFalpha and IL-6 were increased in the n-3 PUFA (P < 0.05) and HCH diet (P <
      0.05, P < 0.01, respectively) groups, but not in animals given the HCH + n-3 PUFA
      diet, whereas IFNgamma levels were increased in hypercholesterolaemia (P < 0.05),
      but were unaffected by n-3 PUFA. CONCLUSION: These results demonstrate that the
      major effect of fish oil n-3 PUFA is to lower the TG levels in both normo- and
      hyperlipidaemia. Furthermore, in the hypercholesterolaemic state, fish oil n-3
      PUFA induces additional beneficial changes in the immune and peroxidation
      responses.

PMID- 17032347
TI  - Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus.
AB  - BACKGROUND: A prospective evaluation of the relationship between insulin
      secretion and insulin sensitivity, derived from the fasting state, is needed in
      clinical practice in order to identify the worsening of glucose metabolism. In
      this study the authors examine whether the product of insulin sensitivity and
      insulin secretion, assessed from the fasting state, predicts progression from
      normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from
      impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS
      AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were
      followed up over a 5-year period. Insulin sensitivity was calculated using the
      Belfiore index (B) and insulin secretion by the homeostasis model analysis beta
      cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0)
      pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] -
      3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting
      glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the
      follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to
      IGT and T2DM, respectively. The product B-beta predicts the progression from NGT
      to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3,
      CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts
      progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from
      IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of
      insulin secretion to compensate for decreased insulin sensitivity during
      transition to IGT and T2DM can be successfully assessed with simple measures
      derived from the fasting state. The product B-beta predicts the development to
      IGT and T2DM.

PMID- 17032348
TI  - Randomized comparison of two rescue therapies for Helicobacter pylori infection.
AB  - BACKGROUND: Bismuth salts are not available worldwide. It remains unknown whether
      clarithromycin can replace bismuth salts as an adjuvant agent in the rescue
      regimens for Helicobacter pylori infection. We therefore designed the prospective
      study to compare the efficacies of two rescue therapies for H. pylori infection
      after standard triple therapies. PATIENTS AND METHODS: Ninety-three patients who
      failed H. pylori eradication using proton pump inhibitor plus clarithromycin and
      amoxicillin were randomly assigned to undergo rescue therapy with esomeprazole,
      clarithromycin, tetracycline and metronidazole (ECTM group, n = 46) or
      esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM group, n =
      47). Follow-up endoscopy was performed at 8 weeks after the end of treatment to
      assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated
      both groups had similar eradication rates (ECTM 74% vs. EBTM 77%; P = 0.76) and
      drug compliance (ECTM 94% vs. EBTM 96%; P = 0.68). However, the frequency of
      adverse events in the ECTM group was higher than that in EBTM group (ECTM 57% vs.
      EBTM 36%, P = 0.05). In the EBTM group, eradication rate of metronidazole
      resistant strains was lower than that of metronidazole-susceptible strains
      (67%[8/12] vs. 100%[9/9], P = 0.05). However, eradication rates were similar
      between metronidazole-susceptible and metronidazole-resistant strains in ECTM
      group (69%[9/13] vs. 70%[7/10], P = 1.00). CONCLUSIONS: The new ECTM second-line
      therapy can achieve similar eradication rate as standard EBTM therapy. It may be
      very useful in countries where bismuth salts are not available.

PMID- 17032349
TI  - Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers.
AB  - BACKGROUND: Mortality from renal-cell cancer remains a significant problem with
      an estimated 12,600 deaths in the United States in 2005 even with current
      treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac
      natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long
      acting natriuretic peptide and kaliuretic peptide have significant anti-cancer
      effects in breast, pancreatic, prostate and colon adenocarcinomas. MATERIALS AND
      METHODS: These four peptide hormones plus brain natriuretic peptide (BNP), C
      natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney
      by a different post-translational processing of the atrial natriuretic peptide
      prohormone, were evaluated for their anti-cancer effects in renal carcinomas.
      RESULTS: Dose-response curves revealed a significant (P < 0.0001) decrease in
      human renal carcinoma cells with each 10-fold increase in concentration from 1
      microm to 100 microm of five of these peptide hormones. There was an 81%, 74%,
      66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to
      vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and
      long-acting natriuretic peptide, respectively (P < 0.0001 for each), whereas BNP
      had no effect and CNP decreased renal cancer cell number by 10% (P = 0.04) at
      their 100 microm concentrations. Three days after treatment with these peptide
      hormones, the cancer cells began to proliferate again. The four cardiac hormones
      and urodilatin decreased DNA synthesis from 65-84% (P < 0.00001), whereas BNP and
      CNP decreased DNA synthesis 3% and 12% (both non-significant). Western blots
      revealed for the first time natriuretic peptide receptors (NPR)-A, -B and -C were
      present in the renal cancer cells. CONCLUSIONS: These results indicate that
      urodilatin and the four cardiac hormones have potent anti-cancer effects by
      eliminating up to 81% of renal carcinoma cells within 24 h of treatment.

PMID- 17032350
TI  - Brain site-specific gene expression analysis in Alzheimer's disease patients.
AB  - BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disorder
      that is characterized by a progressive loss of higher cognitive functions. The
      brain of an individual with AD exhibits extracellular senile plaques (SPs) of
      aggregated amyloid-beta peptide (Abeta) and intracellular neurofibrillary tangles
      (NFTs). Given the critical role of neuronal transport of both proteins and
      organelles, it is not surprising that perturbation of microtubule-based transport
      may play a major role in the pathogenesis of AD. MATERIALS AND METHODS: We used
      the cDNA subtraction methodology and in vitro neural cell culture analyses to
      study the meaning of the brain site-specific gene expression pattern in cerebral
      tissue obtained from AD patients and also from control subjects at autopsy.
      RESULTS: We observed that cytoskeleton-associated proteins were down-regulated in
      AD subjects. We also noted an altered expression of the microtubule-associated
      protein 1B (MAP1B), the heat-shock protein (HSP)-90 (a key chaperone molecule),
      the tripartite motif-containing proteins (TRIM)-32/37 (an anti apoptotic enzyme
      with ubiquitin-protein ligase activity) and the Reticulon-3 (a modulator of the
      amyloid-precursor-protein (APP) cleavage) in AD brains. Additional molecular- and
      cell-biological studies revealed that small interfering RNA (siRNA)-mediated down
      regulation of MAP1B expression leads to neuronal cell death in vitro. CONCLUSION:
      Altered expression of MAP1B, HSP90, TRIM32/37 and Reticulon-3 provides new clues
      by which the ubiquitin-proteasome-, the protein-chaperon- and the APP-processing
      systems are disturbed in AD, thus, leading to neuritic amyloid plaques and
      neurofibrillary tangles.

PMID- 17032351
TI  - Acute lung injury following pancreas ischaemia-reperfusion: role of xanthine
      oxidase.
AB  - BACKGROUND: Acute pancreatitis can lead to increased pulmonary vascular
      permeability and respiratory failure. Oxidants (and their generator, xanthine
      oxidase (XO)) play an important role in injuring the structural integrity of the
      pulmonary epithelium and endothelium, but their importance in the induction of
      acute lung injury following pancreas ischaemia-reperfusion (IR) has not been
      defined. MATERIALS AND METHODS: Rats (n = 48) received a regular or a tungsten
      (oxidoreductase inhibitor)-enriched diet for 14 days. Their isolated pancreases
      were then either perfused (controls) or made ischaemic (IR) for 40 min (12
      replicates/group). This was followed by in-series pancreas plus normal isolated
      lung reperfusion for 15 min. Lungs only were subsequently perfused with the 15
      min accumulated pancreas effluents for 45 min. RESULTS: Injury was induced in all
      IR pancreases as expressed by reperfusion pressure, wet-to-dry ratio and amylase
      and lipase concentrations. Tissue XO activity was high and reduced glutathione
      pool was low in the tungsten-free IR pancreases. Pulmonary plateau pressure
      increased by 46% and final PO(2)/FiO(2) decreased by 24%. Capillary pressure and
      weight rose two- to fourfold in lungs paired with IR non-treated pancreases.
      Twofold increases in bronchoalveolar lavage volume and contents, including XO,
      were also recorded in this group of lungs. Lungs exposed to tungsten-treated
      ischaemic pancreas effluents were minimally damaged and tissue XO content was low
      compared to controls. CONCLUSIONS: Ex-vivo acute pancreatitis induces acute lung
      injury via oxidants/antioxidants misbalance, which may be prevented by
      attenuating pancreas oxidative stress.

PMID- 17032352
TI  - Distinct but critical roles for integrin alphaIIbbeta3 in platelet lamellipodia
      formation on fibrinogen, collagen-related peptide and thrombin.
AB  - Integrins are the major receptor type known to facilitate cell adhesion and
      lamellipodia formation on extracellular matrix proteins. However, collagen
      related peptide and thrombin have recently been shown to mediate platelet
      lamellipodia formation when presented as immobilized surfaces. The aims of this
      study were to establish if there exists a role for the platelet integrin
      alpha(IIb)beta(3) in this response; and if so, whether signalling from the
      integrin is required for lamellipodia formation on these surfaces. Real-time
      analysis was used to compare platelet morphological changes on surfaces of
      fibrinogen, collagen-related peptide or thrombin in the presence of various
      pharmacological inhibitors and platelets from 'knockout' mice. We demonstrate
      that collagen-related peptide and thrombin stimulate distinct patterns of
      platelet lamellipodia formation and elevation of intracellular Ca(2+) to that
      induced by the integrin alpha(IIb)beta(3) ligand, fibrinogen. Nevertheless,
      lamellipodia formation on collagen-related peptide and thrombin is dependent upon
      engagement of alpha(IIb)beta(3), consistent with release of alpha(IIb)beta(3)
      ligand(s) from platelet granules. However, the requirement for signalling by the
      integrin on fibrinogen can be bypassed by the addition of thrombin to the
      solution. These observations reveal a critical role for alpha(IIb)beta(3) in
      forming lamellipodia on collagen-related peptide and thrombin which is dependent
      on its ability to function as an adhesive receptor but not necessarily on its
      ability to signal. These results suggest that integrins may play an important
      role in lamellipodia formation triggered by nonintegrin ligands in platelets and
      possibly in other cell types.

PMID- 17032353
TI  - Leadzyme formed in vivo interferes with tobacco mosaic virus infection in
      Nicotiana tabacum.
AB  - We developed a new method for inhibiting tobacco mosaic virus infection in
      tobacco plants based on specific RNA hydrolysis induced by a leadzyme. We
      identified a leadzyme substrate target sequence in genomic tobacco mosaic virus
      RNA and designed a 16-mer oligoribonucleotide capable of forming a specific
      leadzyme motif with a five-nucleotide catalytic loop. The synthetic 16-mer RNA
      was applied with nontoxic, catalytic amount of lead to infected tobacco leaves.
      We observed inhibition of tobacco mosaic virus infection in tobacco leaves in
      vivo due to specific tobacco mosaic virus RNA cleavage effected by leadzyme. A
      significant reduction in tobacco mosaic virus accumulation was observed even when
      the leadzyme was applied up to 2 h after inoculation of leaves with tobacco
      mosaic virus. This process, called leadzyme interference, is determined by
      specific recognition and cleavage of the target site by the RNA catalytic strand
      in the presence of Pb(2+).

PMID- 17032354
TI  - Isoquinoline-1,3,4-trione and its derivatives attenuate beta-amyloid-induced
      apoptosis of neuronal cells.
AB  - Caspase-3 is a programmed cell death protease involved in neuronal apoptosis
      during physiological development and under pathological conditions. It is a
      promising therapeutic target for treatment of neurodegenerative diseases. We
      reported previously that isoquinoline-1,3,4-trione and its derivatives inhibit
      caspase-3. In this report, we validate isoquinoline-1,3,4-trione and its
      derivatives as potent, selective, irreversible, slow-binding and pan-caspase
      inhibitors. Furthermore, we show that these inhibitors attenuated apoptosis
      induced by beta-amyloid(25-35) in PC12 cells and primary neuronal cells.

PMID- 17032355
TI  - The interaction of disturbances and small mammal community dynamics in a lowland
      forest in Belize.
AB  - 1. Three floods (July 2000, August 2002, September 2003) and a hurricane (October
      2001) that occurred in a lowland forest in the southern Maya Mountains of Belize
      presented an opportunity to evaluate the influence of these disturbances on the
      structure of a small mammal assemblage. 2. Four terrestrial and four primarily
      scansorial/arboreal species were trapped July 2000-March 2005 in six grids over
      14 irregularly spaced trapping periods. 3. Community dynamics were characterized
      more by changes in species composition than changes in diversity. The dynamics
      were driven by species-specific variation in abundance, with changes in
      composition generally, but not exclusively, due to the occurrence or
      disappearance of species at low abundance. Despite the disturbances, species
      richness remained relatively constant. Evenness within the assemblage was
      consistently low, primarily as a result of dominance by one species, Heteromys
      desmarestianus. 4. Effects of flooding on community structure were direct but
      relatively brief (< 1 year), and varied with the duration and intensity of
      flooding. Effects from the hurricane were indirect but long-lasting and strongly
      related to severely reduced food resources. 5. This study suggests that long-term
      dynamics in the structure of many animal communities in the tropics often results
      from interactions between direct and indirect effects of disturbance. It also
      suggests that community resistance will depend on variation in disturbance type
      and regime, but resilience will be determined by the life-history characteristics
      of each species.

PMID- 17032356
TI  - Dynamics of mutualist populations that are demographically open.
AB  - 1. Few theoretical studies have examined the impact of immigration and emigration
      on mutualist population dynamics, but a recent empirical study (A.R. Thompson
      Oecologia, 143, 61-69) on mutualistic fish and shrimp showed that immigration can
      prevent population collapse, and that intraspecific competition for a mutualistic
      partner can curb population expansion. To understand in a theoretical context the
      implications of these results, and to assess their generality, we present a two
      species model that accounts explicitly for immigration and emigration, as well as
      distinguishing the impacts of mutualism on birth rates, death rates and habitat
      acquisition. 2. The model confirms that immigration can stabilize mutualistic
      populations, and predicts that high immigration, along with enhanced reproduction
      and/or reduced mortality through mutualism, can cause population sizes to
      increase until habitat availability curbs further expansion. 3. We explore in
      detail the effects of different forms of habitat limitation on mutualistic
      populations. Habitat availability commonly limits the density of both populations
      if mutualists acquire shelter independently. If a mutualist depends on a partner
      for habitat, densities of that mutualist are capped by the amount of space
      provided by that partner. The density of the shelter-provider is limited by the
      environment. 4. If a mutualism solely augments reproduction, and most locally
      produced individuals leave the focal patch, then the mutualism will have a
      minimal effect on local dynamics. If the mutualism operates by reducing rates of
      death or enhancing habitat availability, and there is at least some immigration,
      then mutualism will affect local dynamics. This finding may be particularly
      relevant in marine systems, where there is high variability (among species and
      locations) in the extent to which progeny disperse from natal locations. 5.
      Overall, our results demonstrate that the consequences of immigration and
      emigration for the dynamics of mutualists depend strongly on which demographic
      rate is influenced by mutualism. 6. By relating our model to a variety of
      terrestrial and aquatic systems, we provide a general framework to guide future
      empirical studies of the dynamics of mutualistic populations.

PMID- 17032357
TI  - Effect of emergent aquatic insects on bat foraging in a riparian forest.
AB  - 1. Riparian zones serve several ecological functions for bats. They provide a
      source of prey and likely provide favourable structural habitats and shelter from
      predators. Many studies have shown that bats use the space above streams, ponds
      or riparian vegetation as feeding habitat. These studies, however, have never
      distinguished between the effects of habitat structure and prey availability on
      the foraging activities of bats. Such effects can only be distinguished by an
      experimental approach. We predicted that bat activity along a stream is
      influenced by the number of emerged aquatic insects. 2. We evaluated the response
      of terrestrial consumers, insectivorous bats, to changes in the abundance of
      emergent aquatic insects by conducting a manipulative field experiment. In a
      deciduous riparian forest in Japan, aquatic insect flux from the stream to the
      riparian zone was controlled with an insect-proof cover over a 1.2 km stream
      reach. 3. We estimated the abundance of emergent aquatic and flying terrestrial
      arthropods near the treatment and control reaches using Malaise traps. The
      foraging activity of bats was evaluated in both treatment and control reaches
      using ultrasonic detectors. 4. The insect-proof cover effectively reduced the
      flux of emergent aquatic insects to the riparian zone adjacent to the treatment
      reach. Adjacent to the control reach, adult aquatic insect biomass was highest in
      spring, and then decreased gradually. Terrestrial insect biomass increased
      gradually during the summer at both treatment and control reaches. 5. Foraging
      activity of bats was correlated with insect abundance. In spring, foraging
      activity of bats at the control reach was significantly greater than at the
      treatment reach, and increased at both sites with increasing terrestrial insect
      abundance. 6. Our result suggests that the flux of aquatic insects emerging from
      streams is one of the most important factors affecting the distribution of
      riparian-foraging bats. As is the case with other riparian consumers, resource
      subsidies from streams can directly enhance the performance or population density
      of riparian-dependent bats. To conserve and manage bat populations, it is
      important to protect not only forest ecosystems, but also adjacent aquatic
      systems such as streams.

PMID- 17032358
TI  - From plankton to top predators: bottom-up control of a marine food web across
      four trophic levels.
AB  - 1. Abundant mid-trophic pelagic fish often play a central role in marine
      ecosystems, both as links between zooplankton and top predators and as important
      fishery targets. In the North Sea, the lesser sandeel occupies this position,
      being the main prey of many bird, mammal and fish predators and the target of a
      major industrial fishery. However, since 2003, sandeel landings have decreased by
      > 50%, and many sandeel-dependent seabirds experienced breeding failures in 2004.
      2. Despite the major economic implications, current understanding of the
      regulation of key constituents of this ecosystem is poor. Sandeel abundance may
      be regulated 'bottom-up' by food abundance, often thought to be under climatic
      control, or 'top-down' by natural or fishery predation. We tested predictions
      from these two hypotheses by combining unique long-term data sets (1973-2003) on
      seabird breeding productivity from the Isle of May, SE Scotland, and plankton and
      fish larvae from the Continuous Plankton Recorder survey. We also tested whether
      seabird breeding productivity was more tightly linked to sandeel biomass or
      quality (size) of individual fish. 3. The biomass of larval sandeels increased
      two- to threefold over the study period and was positively associated with
      proxies of the abundance of their plankton prey. Breeding productivity of four
      seabirds bringing multiple prey items to their offspring was positively related
      to sandeel larval biomass with a 1-year lag, indicating dependence on 1-year-old
      fish, but in one species bringing individual fish it was strongly associated with
      the size of adult sandeels. 4. These links are consistent with bottom-up
      ecosystem regulation and, with evidence from previous studies, indicate how
      climate-driven changes in plankton communities can affect top predators and
      potentially human fisheries through the dynamics of key mid-trophic fish.
      However, the failing recruitment to adult sandeel stocks and the exceptionally
      low seabird breeding productivity in 2004 were not associated with low sandeel
      larval biomass in 2003, so other mechanisms (e.g. predation, lack of suitable
      food after metamorphosis) must have been important in this case. Understanding
      ecosystem regulation is extremely important for predicting the fate of keystone
      species, such as sandeels, and their predators.

PMID- 17032359
TI  - Population limitation of the northern red-backed vole in the boreal forests of
      northern Canada.
AB  - 1. Across the vast boreal forests of North America, no population cycles in
      Clethrionomys species occur. In Eurasia, by contrast, some Clethrionomys
      populations of the same species undergo regular 3-5-year cycles. We examined the
      effects of nutrients, food, competitors, predators and climate on population
      limitation in the northern red-backed vole (Clethrionomys rutilus Pallas) in the
      south-western Yukon to determine why this difference occurs. 2. From 1986 to 1996
      we added food, reduced large mammal predators and excluded snowshoe hares (Lepus
      americanus Erxleben) from large plots and found that none of these manipulations
      affected red-backed vole abundance. Adding nutrients as nitrogen, phosphorus and
      potassium (NPK) fertilizer had a slight negative effect, probably acting through
      a reduction in dwarf shrub productivity caused by competition from grasses. 3. We
      monitored weasel populations directly through trapping and indirectly through
      snow tracking. Predation by these vole specialists was irrelevant as a limiting
      factor most of the time because voles in this area do not reach the densities
      needed to sustain weasel populations. Other boreal forest mammal and bird
      predators did not focus on red-backed voles. However, when red-backed vole
      populations increased in the forest and Microtus voles also increased in the
      meadows, weasel populations increased and may have temporarily depressed red
      backed voles in winter. 4. We monitored one major potential food, white spruce
      seeds, but seed fall was not related to population changes in red-backed voles,
      even after mast years. 5. We assessed the impact of weather variables, and the
      average depth of the snow pack during winter (October-March) was correlated
      directly with vole demography, having both direct effects in that year and
      delayed effects in the following year. 6. Our long-term trapping data (1973-96)
      indicate that Clethrionomys populations fluctuated, with peaks following hare
      peaks by 2-3 years. 7. We propose that the key variable limiting these vole
      populations is overwinter survival, and this is a function of overwinter food
      from berries produced during the previous summer by dwarf shrubs. These shrubs
      may be stimulated by abundant moisture from winter snows or by periodic
      fertilization from large quantities of pellets produced at snowshoe hare peaks.

PMID- 17032360
TI  - Prediction of bird-day carrying capacity on a staging site: a test of depletion
      models.
AB  - 1. The carrying capacity of a site for migratory water birds, expressed in bird
      days, can be of particular conservation value. Several attempts have been made to
      model this carrying capacity using ideal free distribution models such as, for
      instance, depletion models, in which the distribution is fully determined by
      exploitative competition. 2. In the tests of depletion models carried out so far,
      no alternative models were compared; rather, one specific model was tested. We
      tested whether bird-days were more in accordance with birds depleting the food
      resource (a1) until a critical food density which just enabled survival or (a2)
      until a threshold food density which renders the site as profitable as an
      alternative site; and birds (b1) satisfying their daily requirements or (b2)
      maximizing daily intake. 3. We studied Bewick's swans feeding on below-ground
      tubers of fennel pondweed in one part of an autumn staging site. In most years
      between 1995 and 2005, we measured tuber biomass densities around September,
      November and March, and counted swans daily during their stopover in October. 4.
      The best fit between observed and predicted bird-days was obtained by assuming
      that the swans were maximizing their daily intake and depleting the tubers until
      a threshold biomass density (which yielded the same energetic return as the
      alternative food source after accounting for a small part of the initial tuber
      biomass being out of reach of the swans). Also in line with daily intake
      maximization, the daily feeding time did not differ from 10 h day(-1), the value
      predicted for Bewick's swans based on their feeding costs. 5. Our results
      suggests that the applicable model to calculate carrying capacity may depend
      strongly on whether birds use a site to stopover or to winter, because it
      determines whether the birds are more likely to use a threshold or critical food
      density, and to behave as energy maximizers or satisficers.

PMID- 17032361
TI  - Why do female migratory birds arrive later than males?
AB  - 1. In migratory birds males tend to arrive first on breeding grounds, except in
      sex-role reversed species. The two most common explanations are the rank
      advantage hypothesis, in which male-male competition for breeding sites drives
      stronger selection for early arrival in males than females, and the mate
      opportunity hypothesis, which relies on sexual selection, as early arrival
      improves prospects of mate acquisition more for males than for females. 2. To
      date, theoretical work has focused on selection for early arrival within a single
      sex, usually male. However, if fitness depends on territory quality, selection
      for early arrival should operate on both sexes. Here we use two independent
      modelling approaches to explore the evolution of protandry (male-first arrival)
      and protogyny (female-first arrival) under the rank advantage and mate
      opportunity hypotheses. 3. The rank advantage hypothesis, when operating alone,
      fails to produce consistent patterns of protandry, despite our assumption that
      males must occupy territories before females. This is because an individual of
      either sex benefits if it out-competes same-sex competitors. Rather than
      promoting protandry, the rank advantage mechanism can sometimes result in
      protogyny. Female-female competition is stronger than male-male competition early
      in the season, if females compete for a resource (territories occupied by males)
      that is initially less common than the resource of interest to males (unoccupied
      territories). 4. Our results support the mate opportunity hypothesis as an
      explanation of why protandry is the norm in migratory systems. Male-biased adult
      sex ratios and high levels of sperm competition (modelled as extra-pair young:
      EPY) both produce protandry as a result of sexual selection. Protogyny is only
      observed in our models with female-biased sex ratios and low EPY production. 5.
      We also show that the effects of sex ratio biases are much stronger than those of
      EPY production, explore the evidence for sex ratio biases and extra-pair
      paternity in migratory species and suggest future research directions.

PMID- 17032362
TI  - Determinants of quality in a long-lived colonial species.
AB  - 1. In many animal populations a small proportion of individuals produce the
      majority of surviving offspring, but the underlying mechanisms are unclear.
      Behaviour may be an important determinant of variation in fitness: 'high-quality'
      individuals may have enhanced abilities in foraging or predator and parasite
      avoidance. 2. The role of behaviour in determining variation in quality was
      examined using the common guillemot Uria aalge, a monogamous seabird with
      biparental care. Using a novel mixed model approach, we analysed binary data on
      breeding success of each pair attempting to breed in each year with variables
      critical to breeding success (timing of breeding; inferred age; breeding
      experience and success; number of nest sites and partners) as fixed effects.
      Random effects for year, male, female and each distinct pairing of a male and a
      female were included in the model, allowing a quality estimate to be derived for
      each individual and pair. A range of behaviours associated with breeding were
      examined in relation to these quality estimates. 3. Breeding success declined
      with timing of breeding, and increased initially with age before declining in old
      age. It increased with previous successful experience, not breeding experience
      per se, until senescence effects became apparent. For males, breeding success
      declined with increasing numbers of mates. 4. The most important behavioural
      determinants of quality operated at the level of the pair, with the time mates
      spent together at the site and chick feeding rates both positively related to
      quality. At the individual level, trip durations and feeding rates were
      associated with female but not male quality, suggesting that pair quality was
      operating principally through the female. However, removal of laying date, the
      most important component in the binomial model, confirmed that the pair effect
      was much larger than the female effect. 5. This study demonstrates the potential
      of mixed modelling to determine quality estimates based on long-term breeding
      histories. The probability of a successful reproductive attempt was explained by
      the timing of breeding, age, successful breeding experience and number of mates.
      Behaviour was an important proximate mechanism underlying quality, in particular
      the foraging abilities of the pair, and the female's contribution to offspring
      provisioning. In species with biparental care, behavioural correlates of quality
      operate most strongly at the scale of the breeding pair, because contributions
      from both individuals are required for a successful outcome.

PMID- 17032363
TI  - Density dependence and the control of helminth parasites.
AB  - 1. The transient dynamics and stability of a population are determined by the
      interplay between species density, its spatial distribution and the positive and
      negative density-dependent processes regulating population growth. 2. Using the
      human-helminth parasite system as an example, we propose that the life-stage upon
      which negative density dependence operates will influence the rate of host
      reinfection following anthelmintic chemotherapy, and the likely success of
      control programmes. 3. Simple deterministic models are developed which highlight
      how a parasite species whose population size is down-regulated by density
      dependent establishment will reinfect a host population at a faster rate than a
      species with density-dependent parasite fecundity. 4. Different forms of density
      dependence can produce the same equilibrium behaviour but different transient
      dynamics. Under-representing the nature and magnitude of density-dependent
      mechanisms, and in particular those operating upon establishing life-stages, may
      cause the resilience of the parasite population to a control perturbation to be
      underestimated.

PMID- 17032364
TI  - The role of group size and environmental factors on survival in a cooperatively
      breeding tropical passerine.
AB  - 1. Variation in survival, a major determinant of fitness, may be caused by
      individual or environmental characteristics. Furthermore, interactions between
      individuals may influence survival through the negative feedback effects of
      density dependence. Compared to species in temperate regions, we have little
      knowledge about population processes and variation in fitness in tropical bird
      species. 2. To investigate whether variation in survival could be explained by
      population size or climatic variables we used capture-recapture models in
      conjunction with a long-term data set from an island population of the
      territorial, cooperatively breeding Seychelles warbler (Acrocephalus
      sechellensis). The lack of migration out of the study population means that our
      results are not confounded by dispersal. 3. Annual survival was high, both for
      adults (84%) and juveniles (61%), and did not differ between the sexes. Although
      there was significant variation in survival between years, this variation could
      not be explained by overall population size or weather variables. 4. For
      territorial species, resource competition will work mainly on a local scale. The
      size of a territory and number of individuals living in it will therefore be a
      more appropriate measure of density than overall population density.
      Consequently, both an index of territory quality per individual (food
      availability) and local density, measured as group size, were included as
      individual covariates in our analyses. 5. Local density had a negative effect on
      survival; birds living in larger groups had lower survival probabilities than
      those living in small groups. Food availability did not affect survival. 6. Our
      study shows that, in a territorial species, although density-dependent effects
      might not be detectable at the population level they can be detected at the
      individual territory level - the scale at which individuals compete. These
      results will help to provide a better understanding of the small-scale processes
      involved in the dynamics of a population in general, but in particular in
      tropical species living in relatively stable environments.

PMID- 17032365
TI  - Are ectoparasite communities structured? Species co-occurrence, temporal
      variation and null models.
AB  - 1. We studied temporal variation in the structure of flea communities on small
      mammalian hosts from eastern Slovakia using null models. We asked (a) whether
      flea co-occurrences in infracommunities (in the individual hosts) in different
      hosts as well as in the component communities (in the host species) demonstrate a
      non-random pattern; (b) whether this pattern is indicative of either positive or
      negative flea species interactions; (c) whether this pattern varies temporally;
      and (d) whether the expression of this pattern is related to population size of
      either fleas or hosts or both. 2. We constructed a presence/absence matrix of
      flea species for each temporal sample of a host species and calculated four
      metrics of co-occurrence, namely the C-score, the number of checkerboard species
      pairs, the number of species combinations and the variance ratio (V-ratio). Then
      we compared these metrics with the respective indices calculated for 5000 null
      matrices that were assembled randomly using two algorithms, namely fixed-fixed
      (FF) and fixed-equiprobable (FE). 3. Most co-occurrence metrics calculated for
      real data did not differ significantly from the metrics calculated for simulated
      matrices using the FF algorithm. However, the indices observed for 42 of 75
      presence/absence matrices differed significantly from the null expectations for
      the FE models. Non-randomness was detected mainly by the C-score and V-ratio
      metrics. In all cases, the direction of non-randomness was the same, namely the
      aggregation, not competition, of flea species in host individuals and host
      species. 4. The inclusion or exclusion of the uninfested hosts in the FE models
      did not affect the results for individual host species. However, exclusion of the
      uninfested host species led to the acceptance of the null hypothesis for only six
      of 13 temporal samples of the component flea communities for which non-randomness
      was detected when the uninfested hosts were included in the analysis. 5. In most
      host species, the absolute values of the standardized size effect of both the C
      score and V-ratio increased with an increase in host density and a concomitant
      decrease in flea abundance and prevalence. 6. Results of this study demonstrated
      that (a) flea assemblages on small mammalian hosts were structured at some times,
      whereas they appeared to be randomly assembled at other times; (b) whenever non
      randomness of flea co-occurrences was detected, it suggested aggregation but
      never segregation of flea species in host individuals or populations; and (c) the
      expression of structure in flea assemblages depended on the level of density of
      both fleas and hosts.

PMID- 17032366
TI  - Reproductive performance in grey seals: age-related improvement and senescence in
      a capital breeder.
AB  - 1. Three hypotheses have been advanced to account for age-related improvement in
      performance: the selection hypothesis predicts improved due to the loss of lower
      quality phenotypes, the constraint hypothesis predicts individuals improve
      function, and the restraint hypothesis predicts younger individuals forego or
      reduce effort because of mortality risks. A decline in age-related performance
      (i.e. senescence) is predicted by mutation accumulation, antagonistic pleiotropy
      and disposable soma (wear and tear) hypotheses. 2. Using five measures of
      performance - birth rate, maternal and pup birth mass, pup weaning mass, weaning
      success and lactation length - we tested these hypotheses concerning age-related
      change in reproduction in 279 female grey seals (Halichoerus grypus), ages 4-42
      years, over a 23-year period between 1983 and 2005 on Sable Island, Nova Scotia.
      These females produced 2071 pups. 3. Although body mass of primiparous females
      increased with age (4-7 years) birth mass of their pups did not, but pup weaning
      mass did. Second- and third-parity females of the same age as primiparous females
      gave birth to and weaned heavier pups. However, parity and age were dropped from
      models when maternal body mass was included. 4. The proportion of females giving
      birth varied significantly with maternal age, increasing in young females and
      then declining late in life. Weaning success rate also increased rapidly to about
      8 years and subsequently declined in females > 32 years. 5. Generalized additive
      models indicated nonlinear changes in 3 day body mass (i.e. approximately birth
      mass) and weaning mass of pups as a function of maternal age, after accounting
      statistically for the effects of maternal body mass. Mixed-effects, repeated
      measures models fitted to longitudinal data further supported the conclusion that
      pup birth mass and weaning mass vary nonlinearly with maternal age and indicated
      nonlinear changes in lactation duration. 6. We found some support for the
      constraint hypothesis, but our findings were not consistent with the selection
      hypothesis or the restraint hypothesis as the basis for improvement in
      reproductive performance. 7. Senescence was evident in multiple female and
      offspring traits, indicating the degeneration in function of several
      physiological systems as predicted by the disposable soma hypothesis.

PMID- 17032367
TI  - Income breeding allows an aquatic snake Seminatrix pygaea to reproduce normally
      following prolonged drought-induced aestivation.
AB  - 1. Capital breeding is an ideal reproductive strategy for many ectotherms because
      it provides a disassociation between feeding and reproduction, a necessary
      requirement for animals that become anorexic during pregnancy. Among ectotherms,
      some viviparous snakes (e.g. Viperidae) exemplify the capital breeding strategy
      because many species (i) do not feed during pregnancy due to behavioural
      conflicts between reproduction and foraging, and (ii) take more than one season
      to accumulate sufficient energetic stores for reproduction. 2. Isolated wetlands
      often exhibit extreme annual fluctuations in environmental conditions with
      prolonged droughts periodically leaving wetlands completely dry and devoid of
      prey. Following droughts, however, wetlands can be extremely productive,
      rendering prey resources virtually unlimited for some species. 3. This study
      examines drought survival strategy and reproductive ecology of a small aquatic
      snake Seminatrix pygaea (Cope) in an isolated wetland. Seminatrix pygaea are
      atypical from most sympatric snake species in that (i) their small body size,
      reliance on aquatic prey, and high rates of evaporative water loss make them ill
      suited to overland movement, and (ii) they may not be subject to costs typically
      associated with feeding during pregnancy. 4. We hypothesized that S. pygaea would
      survive periodic multiyear droughts by aestivating within the dried wetland, a
      survival strategy heretofore undocumented in snakes. Further, we hypothesized
      that if S. pygaea rely on 'typical' snake reproductive strategies of 'adaptive
      anorexia' and capital breeding, reproductive output would be reduced in the first
      wet year following drought. 5. By encircling a 10-ha wetland with a continuous
      drift fence before it refilled we were able to demonstrate that S. pygaea were
      present within the dried wetland prior to the onset of spring rains that refilled
      the wetland in 2003. Our results suggest that S. pygaea are capable of surviving
      multiyear droughts by aestivating within the dried wetland. 6. Despite having
      presumably depleted energy reserves during the drought, S. pygaea reproduced with
      the same frequency and fecundity during the first season following refilling of
      the wetland as in pre-drought years. 7. The ability of S. pygaea to rebound
      rapidly from the stresses of prolonged drought is due in part to their
      reproductive ecology. Seminatrix pygaea readily feed throughout pregnancy and
      consequently can rapidly translate high prey abundances into reproductive output
      through income breeding.

PMID- 17032368
TI  - A test of the reproductive cost hypothesis for sexual size dimorphism in Yarrow's
      spiny lizard Sceloporus jarrovii.
AB  - 1. Trade-offs between reproduction and growth are central assumptions of life
      history theory, but their implications for sexual size dimorphism (SSD) are
      poorly understood. 2. Adult male Yarrow's spiny lizards Sceloporus jarrovii
      average 10% larger than adult females. In a low-altitude (1700 m) population,
      this SSD develops because males grow more quickly than females during the first
      year of life, particularly during the first female reproductive season. This
      study tests the hypothesis that SSD develops because female growth is constrained
      by energetic costs of reproduction. 3. To test for a growth cost of reproduction,
      I compared growth rates of free-living females that differed, either naturally or
      experimentally, in reproductive status. Females that naturally delayed
      reproduction until their second year grew more quickly than females that
      reproduced as yearlings, and ovariectomized yearlings grew more quickly and to
      larger sizes than reproductive controls. 4. To determine whether SSD develops in
      the absence of this inferred reproductive cost, I also studied a high-altitude
      (2500 m) population in which all females delay reproduction until their second
      year. Sex differences in growth trajectories were similar to those observed at
      low altitude, such that males averaged 10% larger than females even prior to
      female reproduction. 5. Although female growth may be constrained by
      reproduction, multiple lines of evidence indicate that this cost is insufficient
      to explain the full magnitude of SSD in S. jarrovii. First, differences in growth
      of reproductive and nonreproductive females are not observed until the final
      month of gestation, by which time SSD is already well developed. Second, the
      growth benefit accruing from experimental inhibition of reproduction accounts for
      only 32% of the natural sex difference in body size. Finally, SSD develops well
      in advance of female reproduction in a high-altitude population with delayed
      maturation.

PMID- 17032369
TI  - Experimental evidence that the introduced fire ant, Solenopsis invicta, does not
      competitively suppress co-occurring ants in a disturbed habitat.
AB  - 1. The fire ant, Solenopsis invicta, is a globally distributed invasive ant that
      is largely restricted to disturbed habitats in its introduced range. For more
      than half a century, biologists have believed its success results from superior
      competitive abilities relative to native ant species, as well as an escape from
      their natural enemies. 2. We used large volumes of hot water to kill fire ant
      colonies, and only fire ant colonies, on experimental plots in pastures, and
      found that populations and diversity of co-occurring ants did not subsequently
      increase. 3. These results are contrary to classical predictions and indicate
      that S. invicta is not a superior competitor that suppresses native ants, and
      that the low diversity and abundance of native ants in degraded ecosystems does
      not result from interaction with fire ants. Instead, other factors such as prior
      disturbance and recruitment limitation may be the primary limiting factors for
      native species in these habitats.

PMID- 17032370
TI  - The contributions of age and sex to variation in common tern population growth
      rate.
AB  - 1. The decomposition of population growth rate into contributions from different
      demographic rates has many applications, ranging from evolutionary biology to
      conservation and management. Demographic rates with low variance may be pivotal
      for population persistence, but variable rates can have a dramatic influence on
      population growth rate. 2. In this study, the mean and variance in population
      growth rate (lambda) is decomposed into contributions from different ages and
      demographic rates using prospective and retrospective matrix analyses for male
      and female components of an increasing common tern (Sterna hirundo) population.
      3. Three main results emerged: (1) subadult return was highly influential in
      prospective and retrospective analyses; (2) different age-classes made different
      contributions to variation in lambda: older age classes consistently produced
      offspring whereas young adults performed well only in high quality years; and (3)
      demographic rate covariation explained a significant proportion of variation in
      both sexes. A large contribution to lambda did not imply a large contribution to
      its variation. 4. This decomposition strengthens the argument that the
      relationship between variation in demographic rates and variation in lambda is
      complex. Understanding this relationship and its consequences for population
      persistence and evolutionary change demands closer examination of the lives, and
      deaths, of the individuals within populations within species.

PMID- 17032371
TI  - Distribution of a naturally fluctuating ungulate population among heterogeneous
      plant communities: ideal and free?
AB  - 1. Herbivore distribution is often assumed to follow the ideal free distribution
      (IFD) model. This assumes that organisms are omniscient about forage quality and
      availability within the area available to them and are free to move, with
      negligible cost, throughout this environment. If this were the case we would
      expect that, at lowest densities, all animals would be found in the best habitat
      patches, with less desirable habitats being occupied stepwise as population
      density increases. We test this using data from a naturally fluctuating
      population of feral Soay sheep. 2. We show that, although the distribution of
      individuals is correlated positively with food quality, in line with patterns
      reported for hill sheep in Scotland, their distribution does not conform to the
      predictions of the IFD model. We argue that it is the dynamic nature of their
      food resource that causes this departure from the predictions of the IFD model
      and make the case that the IFD model, in its unmodified form, is inappropriate
      for use in modelling distribution among patches containing dynamic resources.

PMID- 17032372
TI  - Effects of sampling regime on the mean and variance of home range size estimates.
AB  - 1. Although the home range is a fundamental ecological concept, there is
      considerable debate over how it is best measured. There is a substantial
      literature concerning the precision and accuracy of all commonly used home range
      estimation methods; however, there has been considerably less work concerning how
      estimates vary with sampling regime, and how this affects statistical inferences.
      2. We propose a new procedure, based on a variance components analysis using
      generalized mixed effects models to examine how estimates vary with sampling
      regime. 3. To demonstrate the method we analyse data from one study of 32
      individually marked roe deer and another study of 21 individually marked
      kestrels. We subsampled these data to simulate increasingly less intense sampling
      regimes, and compared the performance of two kernel density estimation (KDE)
      methods, of the minimum convex polygon (MCP) and of the bivariate ellipse
      methods. 4. Variation between individuals and study areas contributed most to the
      total variance in home range size. Contrary to recent concerns over reliability,
      both KDE methods were remarkably efficient, robust and unbiased: 10 fixes per
      month, if collected over a standardized number of days, were sufficient for
      accurate estimates of home range size. However, the commonly used 95% isopleth
      should be avoided; we recommend using isopleths between 90 and 50%. 5. Using the
      same number of fixes does not guarantee unbiased home range estimates:
      statistical inferences differ with the number of days sampled, even if using KDE
      methods. 6. The MCP method was highly inefficient and results were subject to
      considerable and unpredictable biases. The bivariate ellipse was not the most
      reliable method at low sample sizes. 7. We conclude that effort should be
      directed at marking more individuals monitored over long periods at the expense
      of the sampling rate per individual. Statistical results are reliable only if the
      whole sampling regime is standardized. We derive practical guidelines for field
      studies and data analysis.

PMID- 17032373
TI  - Interactive effects of environmental stress and inbreeding on reproductive traits
      in a wild bird population.
AB  - 1. Conservation biologists are concerned about the interactive effects of
      environmental stress and inbreeding because such interactions could affect the
      dynamics and extinction risk of small and isolated populations, but few studies
      have tested for these interactions in nature. 2. We used data from the long-term
      population study of song sparrows Melospiza melodia on Mandarte Island to examine
      the joint effects of inbreeding and environmental stress on four fitness traits
      that are known to be affected by the inbreeding level of adult birds: hatching
      success, laying date, male mating success and fledgling survival. 3. We found
      that inbreeding depression interacted with environmental stress to reduce
      hatching success in the nests of inbred females during periods of rain. 4. For
      laying date, we found equivocal support for an interaction between parental
      inbreeding and environmental stress. In this case, however, inbred females
      experienced less inbreeding depression in more stressful, cooler years. 5. For
      two other traits, we found no evidence that the strength of inbreeding depression
      varied with environmental stress. First, mated males fathered fewer nests per
      season if inbred or if the ratio of males to females in the population was high,
      but inbreeding depression did not depend on sex ratio. Second, fledglings
      survived poorly during rainy periods and if their father was inbred, but the
      effects of paternal inbreeding and rain did not interact. 6. Thus, even for a
      single species, interactions between the inbreeding level and environmental
      stress may not occur in all traits affected by inbreeding depression, and
      interactions that do occur will not always act synergistically to further
      decrease fitness.

PMID- 17032374
TI  - Cowpox virus infection in natural field vole Microtus agrestis populations:
      delayed density dependence and individual risk.
AB  - 1. Little is known about the dynamics of pathogen (microparasite) infection in
      wildlife populations, and less still about sources of variation in the risk of
      infection. Here we present the first detailed analysis of such variation. 2.
      Cowpox virus is an endemic sublethal pathogen circulating in populations of wild
      rodents. Cowpox prevalence was monitored longitudinally for 2 years, in
      populations of field voles exhibiting multiannual cycles of density in Kielder
      Forest, UK. 3. The probability that available susceptible animals seroconverted
      in a given trap session was significantly positively related to host density with
      a 3-month time lag. 4. Males were significantly more likely to seroconvert than
      females. 5. Despite most infection being found in young animals (because
      transmission rates were generally high) mature individuals were more likely to
      seroconvert than immature ones, suggesting that behavioural or physiological
      changes associated with maturity contribute to variation in infection risk. 6.
      Hence, these analyses confirm that there is a delayed numerical response of
      cowpox infection to vole density, supporting the hypothesis that endemic
      pathogens may play some part in shaping vole cycles.

PMID- 17032375
TI  - Variations on a theme: sources of heterogeneity in the form of the interspecific
      relationship between abundance and distribution.
AB  - 1. A positive interspecific relationship between abundance and distribution is
      widely considered to be one of the most general patterns in ecology. However, the
      relationship appears to vary considerably across assemblages, from significant
      positive to significant negative correlations and all shades in between. 2. This
      variation has led to the suggestion that the abundance-distribution relationship
      has multiple forms, with the corollary that different patterns may inform about,
      or have different, causes. However, this variation has never been formally
      quantified, nor has it been determined whether the observed variation is
      indicative of sampling error in estimating a single effect or of real
      heterogeneity in such relationships. Here, we use the meta-analytical approach to
      assess variation in abundance-distribution relationships, and to test different
      hypotheses for it. 3. Analysis of 279 relationships found a mean effect size of
      0.655, which was both highly significantly different from zero and indicative of
      a strong positive association between abundance and distribution. However, effect
      sizes were highly heterogeneous, supporting the contention that this relationship
      does indeed have multiple forms. 4. Most notably, relationships vary
      significantly in strength across realms, with the strongest in the marine and
      intertidal, intermediate relationships for terrestrial and parasitic assemblages,
      and the weakest relationships in freshwater systems. Effect sizes in all of the
      aquatic realms are homogeneous, suggesting that realm is an important source of
      the heterogeneity observed across all studies. We posit that this may be because
      the different spatial structure of the environment in each realm affects the
      opportunity for the dispersal of individuals between sites. 5. Some of the
      remaining heterogeneity in effect sizes for terrestrial assemblages could be
      explained by partitioning assemblages by habitat, scale, biogeographical region
      and taxon, but considerable heterogeneity in effect sizes for terrestrial and
      parasitic assemblages remained unexplained.

PMID- 17032376
TI  - Habitat exploration and use in dispersing juvenile flying squirrels.
AB  - 1. Variation in behaviours involved in habitat selection is important for several
      evolutionary and ecological processes. For example, habitat use during dispersal
      may differ from breeding habitat use, and for dispersers the scale of habitat
      familiarity is determined by exploratory behaviour. We studied habitat use and
      exploration of 56 radio-collared juvenile flying squirrels Pteromys volans L.
      within natal home range and during dispersal, and compared habitat use between
      juveniles and 37 adults within breeding home range. 2. Before dispersal, young
      flying squirrels actively moved around the natal site. Surprisingly, long
      distance dispersers explored less than short-distance dispersers, but philopatric
      individuals explored similar distances as dispersers. Females explored less than
      males, although females are the more dispersive sex in flying squirrels. 3. For
      most of the individuals the settlement area was unfamiliar due to long dispersal
      distance. Consequently, direction and distance of exploration were not very
      strong predictors of settlement location. However, individuals familiar with the
      settlement area concentrated exploration to that area. Exploration did not
      correlate with short-term survival. 4. Dispersers preferred breeding habitat
      while dispersing, but were found more often in matrix habitat than juveniles
      within natal, or adults within breeding, home ranges. 5. We conclude that
      familiarity does not determine settlement as much as, for example, availability
      of the habitat for flying squirrels. Based on our results, it also seems clear
      that data on adult habitat use are not enough to predict habitat use of
      dispersing individuals. In addition, our results support the recent view that
      short- and long-distance dispersers may need to be analysed separately in
      ecological and evolutionary analyses.

PMID- 17032377
TI  - Functional imaging of carotid atheromatous plaques.
AB  - Atherosclerotic plaque rupture within the internal carotid artery is an important
      cause of transient ischemic attack (TIA) and stroke. Conventional imaging
      techniques such as ultrasound and angiography provide information about the
      structural consequences of such plaques in terms of luminal stenosis. Most
      clinical trials of carotid surgery and stenting and based on these imaging
      methods. Techniques aimed at imaging the biological 'functional' status of the
      plaque are now emerging. Most of these are based on the premise that inflammatory
      activity is an index of plaque stability. In this article we review potential
      imaging targets from the known molecular biological pathways of atherosclerosis.
      Both conventional imaging techniques and the newer methods are discussed. Recent
      data from position emission tomography (PET) imaging and from the use of
      superparamagnetic iron oxide particles with magnetic resonance (MR) imaging are
      shown.

PMID- 17032378
TI  - A magnetization transfer MRI study of deep gray matter involvement in multiple
      sclerosis.
AB  - BACKGROUND/PURPOSE: Gray matter involvement in multiple sclerosis (MS) is of
      growing interest with respect to disease pathogenesis. Magnetization transfer
      imaging (MTI), an advanced MRI technique, is sensitive to disease in normal
      appearing white matter (NAWM) in patients with MS. DESIGN/METHODS: We tested if
      MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n=
      60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio
      (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm
      gapless slices covering the whole brain. Region-of-interest-derived MTR
      histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were
      obtained. Whole brain MTR was also measured. RESULTS: Mean whole brain MTR and
      the peak position of the NAWM MTR histogram were lower in patients with MS than
      NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n=
      10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the
      subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or
      SP vs. NL. CONCLUSIONS: The MTI technique used in this cohort was relatively
      insensitive to disease in the deep gray matter nuclei despite showing sensitivity
      for whole brain disease in MS. It remains to be determined if other MRI
      techniques are more sensitive than MTI for detecting pathology in these areas.

PMID- 17032379
TI  - Dynamic vascular analysis shows a hyperemic flow pattern in sickle cell disease.
AB  - BACKGROUND: By the age of 20 years, 10% of sickle cell disease (SCD) patients
      have experienced a stroke. It is unclear if SCD stroke is due primarily to
      hemodynamic effects of intracranial stenosis, or metabolic failure from anemia.
      Transcranial Doppler ultrasound (TCD) identifies a SCD subgroup with high stroke
      risk, but high mean flow velocity (MFV) can be due to stenosis or high flow rate,
      as with metabolic hyperemia of severe anemia. Dynamic Vascular Analysis (DVA; New
      Health Sciences, Inc., Bethesda, MD) is a new way to analyze TCD data, with
      potential to separate structural from metabolic causes of high MFV. METHODS:
      Eighty SCD patients, regardless of hemoglobin genotypes, aged 2 to 22 years,
      without clinical stroke or transient ischemic attack (TIA), who had TCD (1/1/02
      to 1/1/04) as part of routine outpatient clinical follow-up, with both the TCD
      report and study videotape available, were included. Waveforms were reviewed and
      marked by protocol, and DVA indices calculated including MFV, pulsatility index
      (PI), systolic acceleration (SA), dynamic flow index (DFI), dynamic pressure
      index (DPI), and dynamic compliance index (DCI). Mean and standard deviation were
      defined for the whole group, and for four subgroups, by age. RESULTS: MFV, DFI,
      and DPI were highest at 6- to 9-year-olds, declining thereafter. The 14- to 22
      year-old group was also compared to a group of healthy young athletes (15- to 22
      years old). SCD patients had higher MFV, lnSA, DFI, DPI, and lower PI and DCI in
      most segments, suggesting global hyperemia. CONCLUSION: This is the first report
      of cross-sectional results of DVA in a cohort of SCD outpatients without prior
      clinical stroke (TIA). These results suggest hyperemia without significant focal
      intracranial stenosis. There were also differences between asymptomatic SCD and
      young athletes, and the MFV, DFI, and DPI were highest at the age of 6 to 9
      years, decreasing as age increased.

PMID- 17032380
TI  - Diagnostic accuracy of MRI for middle cerebral artery stenosis: a postmortem
      study.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) has been widely applied
      in detecting intracranial large artery stenosis, but there have been few
      validation studies to compare with histopathology. The aim of the postmortem
      study is to assess the accuracy of MRI in identifying middle cerebral artery
      (MCA) stenosis. METHODS: We recruited, consecutively, Chinese postmortem
      autopsies in our hospital during 19 months. MRI was performed in the postmortem
      brains to scan the cross-sections of MCAs with barium expanding the artery lumen.
      The MCAs were then removed for histopathologic studies. With histopathology as a
      reference standard, the accuracy of MRI was evaluated, and the correlation
      between MCA stenosis identified by MRI and radiologically or histopathologically
      evident brain infarcts was investigated. RESULTS: Seventy-six consecutive
      autopsies were recruited. The sensitivity and specificity of MRI in detecting
      more than 30% MCA stenosis were 38.6% and 92.2%, with a positive predictive value
      of 87.2% and negative predictive value of 52.2%, and the corresponding values of
      MRI in identifying more than 50% MCA stenosis were 57.1%, 90.8%, 50%, and 83.0%,
      respectively. Both more than 30% and more than 50% MCA stenosis identified by MRI
      were found to be associated with infarctions in the corresponding MCA territory
      (P= 0.001, odds ratio = 4.365, 95% CI: 1.684-11.313; and P= 0.039, odds ratio =
      2.694, 95% CI: 1.139-6.377). CONCLUSIONS: Our study demonstrates the agreement
      between ex vivo MRI and histopathology in identifying MCA stenosis, and the
      correlation between the MCA stenosis identified by MRI and radiologically or
      histopathologically evident brain infarcts.

PMID- 17032381
TI  - Derivation of power M-mode transcranial Doppler criteria for angiographic proven
      MCA occlusion.
AB  - BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing
      occlusion are needed for more reliable TCD performance at bedside in the acute
      stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we
      performed TCD examination for patients with symptoms of cerebral ischemia who
      underwent digital subtraction angiography (DSA). We used a standard insonation
      protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies
      Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices
      (PI), and power M-mode resistance signature (absent, high, or low) in symptomatic
      middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral
      (i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA,
      aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings
      were evaluated with a receiver-operating characteristic (ROC) analysis for
      angiographically proven MCA occlusion. RESULTS: We studied 120 patients with
      acute cerebral ischemia with PMD-TCD examinations prior to or immediately after
      DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055).
      The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly
      predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51).
      High resistance or absent M-mode flow signatures in the proximal MCA were present
      in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low
      resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases
      probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode
      signatures are highly predictive of a negative angiogram for MCA occlusion.
      CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA
      occlusion have been developed based on combination of MFV ratios and M-mode flow
      resistance signatures. Validation of these criteria will require multicenter
      studies.

PMID- 17032382
TI  - Patients with diffusion-perfusion mismatch on magnetic resonance imaging 48 hours
      or more after stroke symptom onset: clinical and imaging features.
AB  - BACKGROUND: Abnormalities in diffusion-weighted (DWI) and perfusion-weighted
      (PWI) magnetic resonance imaging (MRI) are thought to reflect the presence of
      brain tissue at risk for ischemic stroke. Many patients with acute ischemic
      stroke have a mismatch pattern in which the PWI volume is larger than the DWI
      lesion. This mismatch typically resolves over 24-48 hours. Little is known about
      the presence of DWI-PWI mismatch in later stages of stroke. METHODS: This is a
      retrospective study of 122 patients admitted with a diagnosis of acute ischemic
      stroke who had DWI and PWI abnormalities on studies performed within 7 days of
      onset of symptoms. Patients were divided into two groups: those with MRI
      performed <48 hours and those with MRI performed >or=48 hours from onset of
      symptoms. RESULTS: Among 42 patients with MRI performed >or=48 hours after onset
      of stroke symptoms, 15 of 42 (36%) showed a mismatch pattern, compared to 45 of
      80 (56%) in the <48 hours group (P < 0.05). Most of the patients in the >or=48
      hours group with mismatch had large artery occlusive disease and many had
      neurological fluctuations. A subset of these patients were treated with induced
      hypertension and showed clinical improvement. CONCLUSIONS: Some patients have
      persistent DWI-PWI mismatch up to several days after stroke onset. Further
      studies are needed to determine if these patients should be candidates for
      reperfusion therapy.

PMID- 17032383
TI  - Stroke patients with cardiac atrial septal abnormalities: differential infarct
      patterns on DWI.
AB  - BACKGROUND: Stroke mechanism in patent foramen ovale (PFO) and/or atrioseptal
      aneurysm (ASA) remains unclear. We aimed to study the stroke pattern on diffusion
      weighted imaging (DWI), in cryptogenetic stroke according to septal
      abnormalities. METHODS: We prospectively evaluated 314 cryptogenetic strokes.
      Patients were categorized according to transesophageal echocardiography (TEE)
      findings: PFO with ASA, PFO alone, and no abnormalities. The study group
      consisted of 126 patients with acute DWI lesions within the first 7 days after
      the stroke onset. We considered the presence of scattered lesions or a cortico
      subcortical territorial lesion as highly suggestive of an embolic pattern.
      RESULTS: PFO was identified in 77 patients (61%) and no alterations in 49
      patients (39%). TEE revealed ASA in 42 patients (54.5% of PFO patients). An
      "embolic" pattern was depicted in 84 (66.7%) and subcortical in 42 (33.3%). An
      "embolic" pattern was significantly (P= .01) more frequently seen in PFO with ASA
      patients (n= 37;44%) as compared to PFO without ASA (n= 22; 26.2%) or no
      abnormalities (n= 25; 29.8%) on TEE. Univariate analysis revealed that age (P=
      .06), hyperlipidemia (P= .04), degree of shunt on TEE (P= .002), and the presence
      of an ASA (P= .008) were associated with an embolic pattern. After adjusting for
      sex, age, and vascular risk factors, only the presence of PFO, with ASA (OR 7.27;
      95% CI 1.5-35.22 P= .014) was independently associated with an embolic pattern.
      CONCLUSION: In patients with cryptogenetic stroke, the presence of PFO with ASA,
      but not isolated PFO, is associated with an embolic pattern on DWI. These
      findings provide insights into the patho-mechanism of stroke in patients with
      PFO.

PMID- 17032384
TI  - Statin use is independently associated with smaller infarct volume in nonlacunar
      MCA territory stroke.
AB  - BACKGROUND: Studies have shown an association between HMG-CoA reductase
      inhibitors (statins) and improved stroke outcomes, possibly secondary to
      neuroprotective properties. OBJECTIVE: To assess whether patients taking statins
      prior to ischemic stroke have smaller infarcts on magnetic resonance imaging
      (MRI), adjusting for other relevant clinical factors. DESIGN: We retrospectively
      reviewed the Cleveland Clinic Foundation (CCF) Neurology Inpatient Database from
      June 2002 through June 2004. Demographics, medications, stroke subtype, diffusion
      weighted imaging (DWI) infarct volume, admission NIHSS, and hours to MRI were
      collected. Patients with a nonlacunar middle cerebral artery (MCA) territory
      infarct and MRI less than 48 hours from symptom onset were included (n= 143). A
      multivariable linear regression model was constructed to determine independent
      predictors of smaller infarct volume. RESULTS: A total of 143 patients were
      studied, including 38 patients taking statins at the time of their stroke. In
      univariate analysis, patients using statins were significantly more likely to
      have a history of hyperlipidemia, atrial fibrillation, and coronary artery
      disease and to be using coumadin, antiplatelet drugs, and angiotensin-converting
      enzyme inhibitors. Patients on statins had a tendency toward smaller infarcts in
      univariate analysis (median 25.4 cm(3) vs. 15.5 cm(3), P= 0.054). In
      multivariable linear regression analysis statin use, patient age, and TIA within
      the prior 4 weeks were independently associated with smaller DWI volumes; vessel
      occlusion on vascular imaging, and cardioembolic stroke subtype with larger
      infarct size. CONCLUSIONS: Statin use prior to the onset of nonlacunar MCA
      infarction was associated with a smaller infarct volume independent of other
      factors. Further studies utilizing both clinical and radiologic outcomes will be
      required to confirm these findings.

PMID- 17032385
TI  - The thickness and texture of temporal bone in brain CT predict acoustic window
      failure of transcranial Doppler.
AB  - BACKGROUND AND PURPOSE: Although transcranial Doppler (TCD) is useful for
      evaluation and treatment of ischemic stroke, temporal acoustic window failure
      (TAWF) limits its application. We performed this study to reveal whether initial
      brain CT of acute stroke patients predicted TAWF. METHODS: We performed TCD in 92
      acute ischemic stroke patients (57 males, aged 38-84 years) with brain CT scans.
      We measured the thickness (BTW) and evaluated the texture of the temporal bone in
      acoustic windows shown in the CT scan with the use of picture archiving and
      communication system. The bone mineral density (BMD) of the vertebral bodies,
      femurs, and whole body was also measured. RESULTS: Doppler signals were
      adequately obtained in 121 (65.8%) of the 184 middle cerebral arteries (MCA) from
      both cerebral hemispheres. BTW and inhomogeneity of temporal bone, besides age,
      sex, and hypercholesterolemia, was strongly correlated with TAWF. BMD was not
      directly correlated with TAWF, but inhomogeneous temporal bone was correlated
      with lower BMD scores. If the brain CT scan showed thick (BTW >or= 2.7 mm) and
      inhomogeneous temporal bone, the possibility of TAWF was 93.5%, while if brain CT
      scan showed thin (BTW < 2.7 mm) and homogenous temporal bone, it was only 5.4%.
      CONCLUSIONS: The texture as well as the thickness of the temporal bone was the
      most important determinant of TAWF. When acute stroke patients had thin and
      homogeneous temporal bones in initial brain CT scan, TAWF was very rare, and loss
      of MCA signals on TCD specifcally indicated the absence of blood flow in MCA.

PMID- 17032386
TI  - Visualization of venous systems by time-of-flight magnetic resonance angiography.
AB  - BACKGROUND AND PURPOSE: Time-of-flight (TOF) imaging technique depicts strong
      signal from fresh unsaturated magnetization that moves fast into the imaging
      region, and TOF magnetic resonance angiography (MRA) visualizes the arterial
      system using saturation pulse and band. However, TOF MRA can visualize the venous
      system when the flow direction is reversed. METHODS AND PATIENTS: We
      consecutively enrolled patients between June 2002 and February 2003 with an
      internal jugular vein (IJV) and sigmoid sinus (SS) visualized by TOF MRA. Carotid
      Duplex ultrasonography was performed on all patients to check IJV flow
      directions. Gadolinium (Gd)-enhanced MRA and conventional digital subtraction
      angiography were performed in selected patients. RESULTS: The IJVs and SSs of
      eight patients (left = 7, right = 1) were observed by TOF MRA. In these 8
      patients, Duplex ultrasonography confirmed a reversed direction in IJVs. Four of
      the patients underwent Gd-enhanced MRA, which showed proximal innominate vein
      steno-occlusion. CONCLUSIONS: This is the first description of IJV and SS
      visualization by TOF MRA. Clinical implications are discussed.

PMID- 17032387
TI  - Lumbar dural ectasia secondary to spinal fusion: a report of two cases.
AB  - Two cases of lumbar dural ectasia secondary to spinal fusion are presented.
      Background history of dural ectasia is discussed; computed tomography (CT) and MR
      imaging characteristics of dural ectasia are shown and possible causes are
      discussed.

PMID- 17032388
TI  - Cyberknife radiosurgery for basal skull plasmacytoma.
AB  - The Cyberknife delivers frameless image-guided stereotactic radiosurgery to
      intracranial and extracranial tumors. We report our use of Cyberknife
      radiosurgery on a medullary plasmacytoma in the clivus extending into the foramen
      magnum. No acute toxicity was seen during or within 24 hours of treatment, and
      the subject had a complete and durable radiographic response on MRI 12+ months
      after treatment. To our knowledge, this is a first case of successful Cyberknife
      radiosurgery of a medullary plasmacytoma.

PMID- 17032389
TI  - Ischemic stroke in the setting of tuberculous meningitis.
AB  - The clinical syndrome of tuberculous (TB) meningitis leading to ischemic strokes
      is rarely seen today in immunocompetent adults native to North America. This
      entity is also notoriously difficult to diagnose because the presenting symptoms
      are often nonspecific. The authors describe a case of a man with TB meningitis
      which progressed to recurrent ischemic cerebral infarcts.

PMID- 17032390
TI  - Differential expression of E-cadherin in metastatic lesions comparing to primary
      oral squamous cell carcinoma.
AB  - BACKGROUND: The main cause of treatment failure in resectable oral squamous cell
      carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell
      adhesion and motility, and is associated with OSCC progression. The aim of this
      study was to investigate the clinical significance of E-cad expression in OSCC
      with lymph node metastasis which had radical neck dissection done. METHOD:
      Immunohistochemistry was used to detect E-cad expression in normal oral mucosa
      (NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45),
      and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated
      with the clinicopathologic features. RESULTS: E-cadherin immunoreactivity was
      progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It
      decreased significantly in the advanced stages of OSCC. However, the increase in
      E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions
      in relation to primary OSCC. Patients with such increased or positive
      immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis.
      CONCLUSION: The findings suggested a dynamic change in E-cad immunoreactivity
      during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad
      immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15-14.67; P =
      0.040) implied the potential role of mortality predictors for OSCC cases with
      nodal involvement.

PMID- 17032391
TI  - Increased survivin expression in high-grade oral squamous cell carcinoma: a study
      in Indian tobacco chewers.
AB  - BACKGROUND: Oral cancer is one of the five leading sites of cancer in the Indian
      population. In the present study we analyzed the expression of apoptosis
      regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous
      lesions of the buccal mucosa of Indian tobacco chewers. METHOD: Paraffin-embedded
      tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC)
      and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2,
      Bax, and p53 was evaluated using immunohistochemical staining method. RESULTS:
      Thirty-six percent OSCC were found to be positive for nuclear p53 staining while
      none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax
      expression was found to increase with increased grade of malignancy. Increase in
      survivin expression was statistically most significant (P < 0.001). CONCLUSION:
      Increased expression of anti-apoptotic survivin in high-grade tumors suggests
      that survivin is likely to contribute significantly to apoptosis resistance in
      response to therapy.

PMID- 17032392
TI  - Solitary fibrous tumor with atypical histological features occurring in the
      palatine tonsil: an uncommon neoplasm in an uncommon site.
AB  - Solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm that usually
      arises in the pleura. Although this tumor has been described in other sites,
      including the head and neck area, in the oropharynx it is extremely rare. We
      report the first case of a SFT arising from the palatine tonsil of a 62-year-old
      man. The tumor consisted of spindle-shaped cells distributed in a haphazard
      pattern and presented atypical histological features such as hypercellular areas
      and high mitotic count. Immunohistochemical studies showed strong positivity for
      CD34 and bcl-2, and weak positivity for desmin. Smooth muscle actin, S-100
      protein and cytokeratines were negative. The patient was well without disease 1
      year after surgery.

PMID- 17032393
TI  - Immunohistochemical detection of platelet-derived endothelial cell growth
      factor/thymidine phosphorylase and angiopoietins in ameloblastic tumors.
AB  - BACKGROUND: To evaluate the roles of angiogenic factors in the development and
      progression of odontogenic tumors, expression of platelet-derived endothelial
      cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and of angiopoietins in
      ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 11
      tooth germs, 44 ameloblastomas, and five malignant ameloblastic tumors were
      examined immunohistochemically with the use of antibodies against PD-ECGF/TP and
      angiopoietin-1 and -2. RESULTS: Immunohistochemical reactivity for PD-ECGF/TP was
      detected in mesenchymal cells in tooth germs and stromal cells in ameloblastic
      tumors, and the level of immunoreactivity for PD-ECGF/TP was significantly higher
      in ameloblastomas than in tooth germs. Granular cell ameloblastomas showed PD
      ECGF/TP reactivity in granular neoplastic cells as well as in stromal cells.
      Immunoreactivity for angiopoietin-1 and -2 was detected predominantly in
      odontogenic epithelial cells near the basement membrane in tooth germs and in
      benign and malignant ameloblastic tumors. Malignant ameloblastic tumors had
      decreased angiopoietin-1 reactivity and ameloblastic carcinomas had increased
      angiopoietin-2 reactivity as compared with the respective levels in tooth germs
      and ameloblastomas. Immunohistochemical reactivity for angiopoietin-2 was
      slightly higher in follicular ameloblastomas than in plexiform ameloblastomas.
      CONCLUSION: Expression of PD-ECGF/TP and angiopoietin-1 and -2 in tooth germs and
      ameloblastic tumors suggests that these angiogenic factors participate in tooth
      development and odontogenic tumor progression by regulating angiogenesis. Altered
      expression of PD-ECGF/TP and angiopoietins in ameloblastic tumors may be involved
      in oncogenesis, malignant potential, and tumor cell differentiation.

PMID- 17032394
TI  - Giant cell granuloma of the jawbones--a proliferative vascular lesion?
      Immunohistochemical study with vascular endothelial growth factor and basic
      fibroblast growth factor.
AB  - AIM: To estimate the angiogenic activity in central giant cell granuloma (CGCG)
      by immunohistochemical stains for vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF). VEGF and bFGF immunoreactivity of the
      lesional mononuclear (MC) and giant (GC) cells was also investigated. METHOD: The
      study consisted of 41 cases of CGCG. Vascularity was quantified by microvascular
      volume (MVV) as determined by point counting. In five cases of CGCG, regions at
      the surrounding border, which demonstrated reactive vascular-rich inflammatory
      areas, served as control. Immunoreactivity of the MC and GC was assessed as the
      percentage of VEGF- and bFGF-positive cells from the total number of the
      respective cell type. RESULTS: Within CGCG lesions the extent of angiogenesis was
      low; MVV did not exceed 5% for either VEGF (88% of lesions) or bFGF (78% of
      lesions). The mean MVV of VEGF- and bFGF-positive blood vessels was 2.9% +/- 2.4%
      and 3.46% +/- 2.35%, respectively, significantly lower than in the control areas
      (27.5% +/- 7.3% and 28.08% +/- 5.5%, respectively) (P = 0.043). VEGF-positive and
      bFGF-positive MC and GC were found in nearly all lesions and in less than half of
      the lesions, respectively. CONCLUSION: The low mean MVV of VEGF- and bFGF
      positive blood vessels implies low angiogenic activity, which does not support
      the designation of CGCG as a true proliferative vascular lesion. MC and GC
      immunoreactivity for the angiogenic factors is assumed to play an important role
      in the osteoclastogenesis process, thus contributing to additional growth of the
      CGCG lesions.

PMID- 17032395
TI  - RANKL and cathepsin K in diffuse sclerosing osteomyelitis of the mandible.
AB  - BACKGROUND: Diffuse sclerosing osteomyelitis (DSO) of the mandible is
      characterized by mixed bone resorption and formation. METHODS:
      Immunohistopathology of DSO in the clinically acute and subacute phases was
      compared with healthy bone. RESULTS: Receptor activator of nuclear factor kappaB
      ligand (RANKL) was found in DSO lesions. When it was used in vitro to stimulate
      monocytes, cathepsin K expression was observed in mononuclear prefusion
      precursors and in multinuclear giant cells. Similarly, exacerbations of DSO were
      characterized by RANKL and induction of cathepsin K in mononuclear precursor
      cells, which subsequently seem to differentiate into osteoclasts or foreign body
      giant cells. The proportion of bone to soft tissue increased with the duration of
      disease. CONCLUSIONS: RANKL-driven osteoclastogenesis and acidic cysteine
      endoproteinase cathepsin K seem to play important roles in DSO as osteoclast
      mediated bone resorption may represent the primary disease process later followed
      by new bone formation.

PMID- 17032396
TI  - No evidence of hepatitis C virus infection in Serbian patients with oral
      leukoplakia.
AB  - BACKGROUND: A review of the literature reveals controversy regarding the
      relationship between hepatitis C virus (HCV) infection and oral leukoplakia (OL).
      The aim of this study was to determine the frequency of HCV antibodies in
      patients with OL and control subjects resident in Serbia. METHODS: In this cross
      sectional study 73 consecutive patients with histologically proven OL and 90
      control subjects, whose age and gender were matched, were examined for the
      presence of serological evidence of chronic hepatic disease, hepatitis B surface
      antigen (HBsAg) and anti-HCV seropositivity. RESULTS: None of the patients with
      OL or control subjects had antibodies to HCV or HBsAg. All patients with OL and
      control subjects had normal liver function. CONCLUSION: The present data indicate
      that patients with OL resident in Serbia do not have evidence of HCV or HBV
      infection.

PMID- 17032397
TI  - Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal
      zone B-cell lymphoma: a case report.
AB  - Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an
      extremely rare clinical presentation. We report a case of LCH involving the
      bilateral parotid glands in an 81-year-old Japanese female. Pathologically, the
      lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid
      infiltrate and cystic dilatation of the parotid gland duct in addition to nodular
      and diffuse proliferation of LCs. Moreover, both LCs and small T-lymphocytes
      invaded the ductal epithelium forming a lymphoepithelial lesion-like morphology.
      The present case indicates that LCHs should be added to the different diagnosis
      for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type
      involving the salivary glands.

PMID- 17032398
TI  - Verrucous carcinoma of the buccal mucosa: histopathological, cytological and DNA
      cytometric features.
AB  - We describe a patient with an exophytic oral lesion diagnosed as verrucous
      carcinoma. The lesion existed without metastases, at least 5 years. Local
      excisions led to recurrences and continuous expansion. Scalpel biopsies for
      histopathological and polymerase chain reaction examination were obtained from
      characteristic regions of the lesion. Brush biopsies for exfoliative cytology
      (EC) were taken, in order to screen the mucosal area covered by the lesion. After
      Feulgen restaining of the smears, nuclear DNA contents were measured using a TV
      image analysis system. An exophytic lesion of the buccal mucosa was diagnosed as
      low-grade malignant through histopathology and EC combined with DNA-image
      cytometry (peritetraploid DNA-aneuploidy). Due to almost normal microscopic
      appearance of the epithelium of verrucous carcinoma, thorough cytological/DNA
      cytometric and histological examinations are needed. Brush biopsies of such
      neoplastic oral lesions showing DNA-aneuploidy with peritetraploid stemlines
      should be used for diagnosis and follow-up examination of these patients.

PMID- 17032399
TI  - Ligneous alveolar gingivitis in the absence of plasminogen deficiency.
AB  - A case of localized, longstanding, asymptomatic ligneous gingivitis affecting the
      crest of the edentulous lower left posterior alveolar ridge (ligneous alveolar
      gingivitis) of a middle-aged Caucasian woman is presented. This patient did not
      have any associated ophthalmic lesions (ligneous conjunctivitis) and did not have
      a plasminogen deficiency.

PMID- 17032400
TI  - Seckel syndrome associated with oligodontia, microdontia, enamel hypoplasia,
      delayed eruption, and dentin dysmineralization: a new variant?
AB  - Seckel syndrome (SCKL) [OMIM Entry 210600] is a rare, autosomal recessive
      syndrome, characterized by severe intrauterine and postnatal growth retardation,
      microcephaly, mental retardation, and typical facial appearance with beaklike
      protrusion of the midface (bird-headed). Associated findings may include limb
      anomalies, dislocation of femoral heads, scoliosis, and gastrointestinal
      malformation. A 14-year-old boy is presented with brain hypoplasia, pachygyria,
      hydrocephaly, enamel hypoplasia and root dysplasia in the temporary dentition,
      and oligodontia, severe microdontia, and delayed eruption of the permanent
      dentition. The association of SCKL with the above unusual dental findings may
      represent a new phenotype.

PMID- 17032401
TI  - Genes or environment to determine alcoholic liver disease and non-alcoholic fatty
      liver disease.
AB  - While the vast majority of heavy drinkers and individuals with obesity, insulin
      resistance, and the metabolic syndrome will have steatosis, only a minority will
      ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental
      risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty
      liver disease (NAFLD) seem likely to include factors that influence the severity
      of steatosis and oxidative stress, the cytokine milieu, the magnitude of the
      immune response, and/or the severity of fibrosis. For ALD, the dose and pattern
      of alcohol intake, along with obesity are the most important environmental
      factors determining disease risk. For NAFLD, dietary saturated fat and
      antioxidant intake and small bowel bacterial overgrowth may play a role. Family
      studies and interethnic variations in susceptibility suggest that genetic factors
      are important in determining disease risk. For ALD, functional polymorphisms in
      the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes
      play a role in determining susceptibility in Oriental populations. No genetic
      associations with advanced NAFLD have been replicated in large studies.
      Preliminary data suggest that polymorphisms in the genes encoding microsomal
      triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin
      receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be
      associated with steatohepatitis and/or fibrosis.

PMID- 17032402
TI  - How to modulate inflammatory cytokines in liver diseases.
AB  - Most acute and chronic liver diseases are characterized by inflammatory processes
      with enhanced expression of various pro- and anti-inflammatory cytokines in the
      liver. These cytokines are the driving force of many inflammatory liver disorders
      often resulting in fibrosis and cirrhosis. Severe alcoholic hepatitis is a
      prototypic tumor necrosis factor-alpha (TNF-alpha)-associated disease. This
      knowledge has recently led to pilot studies with promising results investigating
      specific anti-TNF drugs such as infliximab or etanercept in the treatment of this
      disease, although a recently performed controlled French study did show a
      potential detrimental effect of this approach. Anti-TNF treatment strategies
      might also improve chronic hepatitis C infection as shown by one controlled trial
      using etanercept administered subcutaneously for 24 weeks. Furthermore, several
      case reports suggest that TNF-alpha neutralization is not harmful to patients
      chronically infected with this virus. In contrast, neutralization of TNF-alpha
      worsens and might even be associated with fatalities in chronic hepatitis B
      infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also
      been tried in patients with chronic liver diseases. Whereas IL-10 administered to
      patients with chronic hepatitis C virus infection shows indeed anti-inflammatory
      effects in the liver, it seems to act as a proviral agent thereby limiting its
      clinical utility. Another cytokine with major anti-inflammatory potential is the
      adipokine adiponectin, as its administration is beneficial in many experimental
      models of liver injury. Interference with cytokine pathways and/or administration
      of anti-inflammatory cytokines will be of major interest in the future therapy of
      many liver diseases.

PMID- 17032403
TI  - Liver involvement in hereditary hemorrhagic telangiectasia: consensus
      recommendations.
AB  - STUDY PURPOSE: To formulate recommendations about clinical management of liver
      involvement in hereditary hemorrhagic telangiectasia (HHT), using a formal
      consensus development process. CONSENSUS PROCESS: A nominal group technique was
      used. A list of main clinical, diagnostic and therapeutic issues about liver
      involvement in HHT was generated by the organizing committee. Panel members then
      scored their agreement with each statement; the median score, and standard
      deviation for each statement were determined for each of the three successive
      panel rounds. These consensus statements formed the basis for recommendations
      graded with the strength and quality of supporting evidence. RECOMMENDATION
      STATEMENTS: Doppler US is sufficiently accurate and suitable for first-line
      imaging of the liver in the general HHT population. Liver biopsy in any patient
      with proven or suspected HHT should be avoided. Liver involvement in HHT is
      generally asymptomatic; in the minority of patients where it is symptomatic,
      morbidity and mortality can be substantial. The prevalence of focal nodular
      hyperplasia is much higher in patients with liver involvement by HHT than in the
      general population. Invasive therapies for liver involvement by HHT (namely liver
      transplantation) should be considered only in patients who have failed to respond
      to intensive medical therapy.

PMID- 17032404
TI  - Racial and ethnic variations in the epidemiology of intrahepatic
      cholangiocarcinoma in the United States.
AB  - BACKGROUND/AIMS: Despite the global increase in the incidence of intrahepatic
      cholangiocarcinoma, regional variations occur. To assess the potential
      contribution of racial/ethnic factors, we assessed the epidemiology of these
      cancers in different racial and ethnic groups in the United States. METHODS:
      Disease prevalence, mortality and survival rates for different racial and ethnic
      groups were obtained from the surveillance, epidemiology and end results survey
      database. RESULTS: The age-adjusted prevalence was highest for Hispanics (1.22
      per 100 000) and lowest for Blacks (0.3 per 100 000). Age-adjusted mortality
      rates were higher for American Indian/Alaska Natives and Asian/Pacific Islanders
      compared with other groups. However, mortality rates increased by greater than
      3.5% annual for all racial or ethnic groups except for American Indian/Pacific
      Islanders in whom mortality rates decreased by 0.2% annually. The increase in
      mortality rates was greatest for Hispanic women aged between 40 and 49 years.
      Prevalence and survival were significantly higher in Hispanic women in contrast
      to gender differences observed in other groups. CONCLUSIONS: Significant racial
      and ethnic variations occur in the epidemiology of intrahepatic
      cholangiocarcinoma within geographically defined regions in the United States
      These may reflect genetic, socioeconomic or cultural predispositions to cancer.

PMID- 17032405
TI  - Quantitative assessment of liver fibrosis: a novel automated image analysis
      method.
AB  - BACKGROUND: Semiquantitative staging of liver fibrosis is a highly subjective
      procedure and may lead to an uncertainty in judgment regarding the degree of
      severity and hence the progression of the disease. AIM: In this work, we present
      an automated quantification system (AQS) for evaluating the degree of severity of
      fibrosis in liver biopsies based on Ishak et al.'s classification. Accordingly,
      liver fibrosis is classified into six classes depending on its severity and
      progression. The described system is of special value in accurately assessing the
      prognosis of chronic liver disease. METHODS: In our method, we tried to
      approximate the architecture of the fibrosis in the subject sample using texture
      features and shape representation of the fibrosis structural expansion with an
      overall accuracy of about 98%. RESULTS AND CONCLUSION: The presented AQS is
      considered to be a novel approach in the domain of automatic liver fibrosis
      quantification. It is a true quantification and intelligent approach that
      attempts to utilize the current semiquantitative methods of liver fibrosis
      assessment to turn them into real quantitative ones with significant reduction in
      variability and subjectivity. We propose that our method can be adopted by a
      panel of expert liver pathologists and software to be developed and used on a
      wide scale.

PMID- 17032406
TI  - Increased expression of Ob-Rb and its relationship with the overexpression of TGF
      beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis.
AB  - AIMS: The main aim of this study was to examine the relationship of the leptin
      system in steatosis and nonalcoholic steatohepatitis (NASH). The study also
      analysed the pathogenic role of the leptin system in the development of hepatic
      fibrosis and its relation with the TGF-beta1 system. MATERIALS AND METHODS: The
      study included 90 subjects, 55 with NASH and 35 with simple steatosis. Gene
      expression of leptin, leptin receptor and TGF-beta mRNA was analysed by real-time
      PCR on liver tissue. Leptin serum levels were determined by RIA. Leptin receptor
      expression was also assessed by immunohistochemistry. RESULTS: Increased
      expression was found for leptin receptor mRNA (P=0.0016) and its protein (P<0.05)
      in patients with NASH, especially those with fibrosis. There was a marked
      increase in gene expression of TGF-beta1 in patients with NASH (P=0.0002). A
      strong correlation was demonstrated between leptin receptor gene expression and
      TGF-beta1 gene expression (P=0.023). No leptin expression was found in the liver
      tissue. All patients showed a marked hyperleptinemia, which was closely related
      to the anthropometric characteristics analysed and independent of development or
      not of NASH. CONCLUSIONS: The results of the study demonstrate for the first time
      increased leptin receptor expression in liver tissue and its relationship with
      overexpression of TGF-beta1 and the degree of hepatic fibrosis.

PMID- 17032407
TI  - Pulmonary blood volume and transit time in cirrhosis: relation to lung function.
AB  - BACKGROUND/AIMS: In cirrhosis a systemic vasodilatation leads to an abnormal
      distribution of the blood volume with a contracted central blood volume. In
      addition, the patients have a ventilation/perfusion imbalance with a low
      diffusing capacity. As the size of the pulmonary blood volume (PBV) has not been
      determined separately we assessed PBV and pulmonary transit time (PTT) in
      relation to lung function in patients with cirrhosis and in controls. METHODS:
      Pulmonary and cardiac haemodynamics and transit times were determined by
      radionuclide techniques in 22 patients with alcoholic cirrhosis and in 12
      controls. The lung function including diffusing capacity for carbon monoxide (DL,
      CO) was determined by conventional single breath technique. RESULTS: In the
      patients, PTT was shorter, 3.9+/-1.2 vs 5.7+/-1.0 s in the controls, P<0.001, and
      the PBV was lower, 362+/-151 vs 587+/-263 ml, in the controls, P<0.005. Both PTT
      and PBV were lowest in patients with advanced disease. DL, CO was reduced in the
      patients and correlated significantly with PTT (r=0.58, P=0.007) and PBV (r=0.49,
      P<0.03). CONCLUSIONS: The results suggest that the reduced PBV contributes to the
      reduced effective blood volume in cirrhosis. The relation between PBV and PTT and
      the low diffusing capacity suggests the pulmonary vascular compartment as an
      important element in the pathophysiology of the lung dysfunction in cirrhosis.

PMID- 17032408
TI  - Anemia associated with antiviral therapy in chronic hepatitis C: incidence, risk
      factors, and impact on treatment response.
AB  - BACKGROUND: One major side effect of combination antiviral therapy is the
      development of anemia, which is more severe among the Asian population. We
      conducted this large-scaled study to explore the incidence, risk factors, and
      impact on treatment response of anemia in chronic hepatitis C patients receiving
      combination antiviral therapy. METHODS: Four hundred and sixty-six chronic
      hepatitis C patients were treated with interferon-alpha-2b (IFN-alpha-2b) three
      or five million units thrice weekly, or pegylated-IFN-alpha-2b 1-1.5 microg/kg
      weekly plus ribavirin (1000-1200 mg/day) for 24 weeks. Severe anemia was defined
      as hemoglobin concentration <10 g/dl. RESULTS: The mean decrease of hemoglobin
      was 3.9+/-1.3 g/dl. Thirty-nine percent of patients had developed severe anemia
      during therapy. Stepwise logistic regression analysis revealed that old age (> or
      =50 years) (odds ratio [OR]=1.935, P=0.001) and baseline hemoglobin level (> or
      =14 g/dl) (OR=2.975, P<0.001) were significantly correlated with maximal
      decreases in hemoglobin. Using Cox's regression analysis, pretreatment platelet
      counts (<150 000/mm(3)) (OR=1.821, P<0.001), old age (> or =50 years) (OR=1.789,
      P=0.001), female gender (OR=1.739, P<0.001), and low body weight (<65 kg)
      (OR=1.493, P=0.027) were independent factors contributing to severe anemia. There
      was a significant linear correlation between the sustained virological response
      (SVR) rate and the time of severe anemia during therapy (r=0.774, P=0.003),
      especially among genotype 1 patients (r=0.960, P<0.001). CONCLUSION: Careful
      monitoring of hemoglobin level is necessary in patients who are old, female and
      have low body weight and platelet counts. Development of severe anemia was
      significantly correlated with the SVR.

PMID- 17032409
TI  - Noninvasive tests for the prediction of significant hepatic fibrosis in hepatitis
      C virus carriers with persistently normal alanine aminotransferases.
AB  - BACKGROUND: The diagnostic value of Doppler and various noninvasive indices in
      predicting significant hepatic fibrosis in hepatitis C virus (HCV) carriers with
      persistently normal alanine aminotransferases (PNALT) is unknown. METHODS:
      Seventy-nine treatment-naive HCV carriers with PNALT, who received Doppler
      ultrasonography and percutaneous liver biopsies, were enrolled in the study.
      Doppler indices, including portal vein velocity (PVV), hepatic arterial resistive
      index (HARI), hepatic arterial pulsatility index (HAPI), splenic arterial
      resistive index (SARI), and splenic arterial pulsatility index (SAPI), were
      compared with known biochemical indices used in HCV carriers with elevated ALT
      levels, including aspartate aminotransferase (AST) to platelet ratio index
      (APRI), age-platelet index (API), and AST to ALT ratio (AAR), for the diagnostic
      accuracy of significant hepatic fibrosis. RESULTS: SAPI was the most
      discriminatory index among the Doppler indices (P<0.001). By comparing areas
      under the receiver-operating characteristic (AUROC) of SAPI with various
      biochemical indices, SAPI was superior to APRI, API, and AAR for predicting
      significant fibrosis (> or =F2) (0.862 vs. 0.673, 0.639, 0.504). SAPI set at 0.85
      and 1.10 had a sensitivity of 96.7% and 66.7%, a specificity of 44.6% and 96.0%,
      a positive predictive value of 41.4% and 87.1%, and an negative predictive value
      of 97% and 87.7% in predicting significant fibrosis. CONCLUSIONS: This study
      indicates that SAPI is the most useful index among Doppler and biochemical
      indices for the detection of significant hepatic fibrosis in HCV carriers with
      PNALT levels.

PMID- 17032410
TI  - Noninvasive serum markers in the diagnosis of structural liver damage in chronic
      hepatitis C virus infection.
AB  - AIM: Several noninvasive markers are being used to assess the structural liver
      damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of
      serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST
      to platelet ratio index (APRI) and gamma-glutamyltransferase (GGT) levels to
      predict the intensity of hepatic fibrosis in patients with CHC. PATIENTS AND
      METHODS: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST,
      ALT, GGT levels, platelet count and serum HA concentration were determined. The
      APRI was calculated as the ratio of AST to platelets. RESULTS: HA levels were
      best correlated with disease stage (r=-0.694; P<0.001). In the diagnosis of
      significant fibrosis (F2-F4), HA levels [AUC=0.879, 95% CI (0.832-0.927)] and
      APRI [AUC=0.824 (0.772-0.903)] were the markers with the best diagnostic
      accuracy. These parameters also best identified the presence of cirrhosis (F4),
      with an AUC of 0.908 (0.868-0.949) for HA and of 0.837 (0.772-0.903) for APRI.
      CONCLUSION: Serum HA was the parameter that alone presented the best diagnostic
      accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better
      diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple
      determination and low cost make this index a valid alternative for the
      noninvasive staging of CHC.

PMID- 17032411
TI  - Differential expression of toll-like receptor mRNA in treatment non-responders
      and sustained virologic responders at baseline in patients with chronic hepatitis
      C.
AB  - BACKGROUND/AIMS: The contribution of the host immune response to sustained
      virologic response is not clear in patients with chronic hepatitis C (CHC). The
      aim of this study was to explore the relationship of the toll-like receptor (TLR)
      expression with the outcome of antiviral therapy in hepatitis C viral infection.
      METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC
      patients before a 48-week treatment with pegylated interferon (PEG IFN) alpha-2a
      and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase
      chain reaction (RT-PCR) was used to compare the relative abundance of TLR2-9
      transcripts. RESULTS: mRNA levels of TLR2, 3 and 6 were significantly higher in
      CHC subjects compared with normal controls (n=8). When patients were classified
      into non-responders (n=8) and sustained virological responders (n=7) according to
      the virological outcome of the treatment, there was a clear difference in
      baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition,
      the mRNA expression of IFN-gamma and nuclear factor of activated T cells (NFAT),
      which is exclusively expressed in activated T cells, was inversely correlated
      with that of TLR4, 6 and 9 in non-responders. CONCLUSIONS: TLRs mRNA levels are
      differentially expressed in baseline PBMC of chronic HCV-infected subjects with
      or without responsiveness to antiviral therapy.

PMID- 17032412
TI  - Zinc is a negative regulator of hepatitis C virus RNA replication.
AB  - BACKGROUND/AIMS: Hepatitis C virus (HCV) infection is a significant global public
      health problem. In clinical studies, zinc has been closely related to the
      pathogenesis of chronic hepatitis C. However, the role of zinc in both viral
      replication and the expression of viral proteins remains unclear. We aimed to
      clarify the effect of zinc on the replication of HCV in vitro. METHODS: We
      incubated subgenomic HCV replicon cells (sO) and genome-length HCV RNA
      replicating cells (O) treated with several chemicals including trace elements.
      Total RNAs were collected and subjected to real-time reverse-transcriptase
      polymerase chain reaction in order to examine the level of HCV RNA replication,
      and Western blotting was performed to confirm the expression of viral proteins.
      RESULTS: Iron salts and interferon-alpha suppressed HCV RNA replication and
      protein expression in both sO and O cells. Zinc salts effectively reduced the
      viral replication in the genome-length HCV RNA replication system but not in the
      subgenomic HCV replicon system. CONCLUSIONS: We demonstrated that zinc may play
      an important role as a negative regulator of HCV replication in genome-length HCV
      RNA-replicating cells. Zinc supplementation thus appears to offer a novel
      approach to the development of future strategies for the treatment of intractable
      chronic hepatitis C.

PMID- 17032413
TI  - Impact of liver steatosis on the antiviral response in the hepatitis C virus
      associated chronic hepatitis.
AB  - BACKGROUND/AIM: Liver steatosis (LS) has been variably associated with chronic
      hepatitis C (CHC) but whether it affects sustained virological response to
      antiviral treatment and by what mechanisms is a question still under debate, at
      least for some genotypes. The aim of this work was to assess the frequency of LS,
      its relationship with host and viral factors and to what extent it can influence
      the response to antiviral combination therapy with pegylated interferon
      (INF)+ribavirin in a group of patients with CHC from a single center. PATIENTS:
      One hundred and twelve patients with histologically proven CHC were treated with
      Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin
      1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded
      according to Brunt et al. RESULTS: Forty-six out of 112 patients (41.1%) were
      sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented
      with LS at histology; in this group, there were 24 patients (33.3%) with SVR
      compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables
      associated with the steatosis group were: higher serum levels of AST (P<0.04),
      alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and
      severity of histology (staging P<0.05) but at multiple linear regression analysis
      only genotype 3a and staging were significantly associated with LS. In the SVR
      group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03,
      respectively) compared with non-responders; moreover, genotype 1 was more
      frequent in the NR group, while genotype 3 was more frequent in the SVR group. At
      histology, grading and staging were also lower in the SVR group. Multiple
      logistic regression showed that only the grade of steatosis and genotype 3a were
      the variables independently associated with SVR. CONCLUSIONS: This study showed a
      frequency of LS on the higher side of the range so far reported in the literature
      and confirmed that it negatively influences response to therapy. Genotype1 was
      confirmed to be the most frequent type in our area. It is more frequent in
      patients with mild-moderate steatosis and seems to condition therapeutic response
      negatively, together with BMI and age. In contrast, genotype 3a is more frequent
      in patients with severe steatosis, but is a favorable predictor of successful
      therapy.

PMID- 17032414
TI  - Differential expression genes analyzed by cDNA array in the regulation of rat
      hepatic fibrogenesis.
AB  - PURPOSE: To analyze the gene expression pattern in rat hepatic fibrogenesis and
      further assess the role of some key genes during the pathological process.
      METHODS: Hepatic fibrosis was induced by intraperitoneal injection of
      dimethylnitrosamine or carbon tetrachloride (CCl(4)) injection subcutaneously in
      rats, and identification of the hepatic fibrosis related genes with cDNA
      microarray was performed. After some key genes up-regulated during the
      development of hepatic fibrosis were screened and confirmed, their effects on the
      function of the activated rat hepatic stellate cells (HSC) were assessed using
      the small interfering RNA (siRNA) technique. RESULTS: Using an Atlas rat cDNA
      array, a number of differentially expressed genes in fibrotic liver tissues were
      identified compared with non-diseased control. A total of 15 genes predominantly
      associated with the mitogen-activated protein kinase (MAPK) signal transduction
      pathway were upregulated in the fibrotic liver. Immunohistochemical study
      revealed that the expressions of both extracellular signal-regulated kinases
      (ERK) and ribosomal protein S6 kinase (RSK), two of the key genes in the MAPK
      pathway, were remarkably induced, which was closely correlated to that of
      collagen types I and III during the development of hepatic fibrosis. Transfection
      of siRNA targeting ERK1 mRNA (siERK1) into HSC led to a 66% and 72% reduction of
      ERK1 mRNA and protein expression, respectively. Furthermore, siERK1 exerted the
      inhibition of the proliferation of HSC, accompanied by the induction of HSC
      apoptosis and reduction of collagen types I and III. In addition, siERK1
      abolished the effect of platelet-derived growth factor-BB on the proliferation of
      HSC. CONCLUSIONS: The present study provided strong evidence for the
      participation of the MAPK pathway in the pathogenesis of hepatic fibrosis.
      Selective targeting of ERK1 inhibitors to HSC might present as a novel strategy
      for the treatment of hepatic fibrosis.

PMID- 17032415
TI  - Systemic mediators induce fibrogenic effects in normal liver after partial bile
      duct ligation.
AB  - BACKGROUND/AIMS: Collagen production by activated hepatic stellate cells (HSCs)
      is a key event in liver fibrosis, and a number of factors have been characterized
      that trigger HSC activation and collagen production. However, it remains unclear
      if these factors act locally at the site of injury or also affect HSCs distant to
      the site of injury. METHODS: A model of partial bile duct ligation (PBDL) in
      which fibrogenesis can be compared between the injured ligated lobe and the non
      ligated lobe. RESULTS: After PBDL, HSCs showed an increased expression of
      procollagen type I alpha1 mRNA and collagen-reporter gene activity not only in
      the ligated lobe, but also in the non-ligated lobe, albeit at a lower level. In
      contrast, an increase in the number of desmin- and alpha-smooth muscle actin
      positive HSCs, and accumulation of inflammatory cells were observed only in the
      ligated lobe. Although transforming growth factor-beta (TGF-beta) mRNA was
      increased only in the ligated lobe, Smad2/3 were activated in the ligated and the
      non-ligated lobe. These data suggest that the systemic increase in profibrogenic
      mediators including TGF-beta induces collagen transcription in the uninjured
      liver. CONCLUSION: Systemic profibrogenic mediators from the injury site affect
      the residual non-injured liver.

PMID- 17032418
TI  - Should children ever be living kidney donors?

PMID- 17032416
TI  - Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis
      C.
AB  - BACKGROUND/AIM: Pegylated interferon (Peg-IFN) plus ribavirin is the standard
      therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role
      in hepatitis C treatment seems to be related to its immunomodulatory effect.
      Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both
      drugs are associated with adverse reactions of different magnitudes. Autoimmune
      phenomena have been reported with this treatment. In this paper, we describe
      cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to
      the appearance of anti-Golgi antibody and disease progress. METHODS: We
      investigated three patients with hepatitis C and severe ALT/GGT flares during Peg
      IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the
      only marker of autoimmunity. We then reviewed the medical files and tested anti
      Golgi antibody in stored sera from 25 patients treated with conventional IFN and
      in 14 patients treated with Peg-IFN. RESULTS: The three patients were male, over
      45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was
      positive during treatment coinciding with ALT/GGT flares but with hepatitis C
      virus (HCV)-RNA negativity, disappearing after stopping treatment, with
      normalization of ALT/AST levels. One patient had progression of fibrosis from F2
      to F3 despite negativity of HCV-RNA. In the last group, only two patients treated
      with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody
      CONCLUSIONS: The presence of anti-Golgi complex antibody could be a marker of a
      temporary autoimmune phenomenon and progressive disease.

PMID- 17032417
TI  - Redefining reference limits needs more attention to the analytical aspects.

PMID- 17032419
TI  - Protocol biopsies should be standard of care for pediatric renal allograft
      recipients!

PMID- 17032420
TI  - Protocol biopsies should not (yet) be the standard of care in pediatric renal
      transplant recipients.

PMID- 17032421
TI  - Anticoagulation post-renal transplant: is it indicated?

PMID- 17032422
TI  - Evaluation and management of patients with propionic acidemia undergoing liver
      transplantation: a comprehensive review.
AB  - Propionic acidemia is a rare metabolic disorder that often results in episodic
      hyperammonemia, basal ganglia infarction, mental retardation, and cardiomyopathy.
      OLT has been used as a treatment for propionic acidemia, but its benefit in
      patients with this disease is unclear. The current study was undertaken to
      clarify the role of OLT in the management of this disease. The medical
      literature, a national registry of US OLT recipients, and a single institution
      liver transplant experience were reviewed for cases of OLT for propionic
      acidemia. Accumulated cases demonstrate that OLT has resulted in clear evidence
      of clinical improvement in several patients, often obviating the need for dietary
      restriction or other forms of medical management. OLT appears to halt the decline
      in neurocognitive function often associated with propionic acidemia. In total, 12
      patients with propionic acidemia have undergone a total of 14 OLTs. A
      quantitative analysis of outcomes shows an overall patient survival rate of 72.2%
      at one year after OLT. In conclusion, OLT should be considered a treatment option
      for patients with propionic acidemia who continue to experience episodes of
      hyperammonemia in spite of maximal medical therapy. Early OLT may limit the
      development of mental retardation and/or cardiomyopathy.

PMID- 17032423
TI  - Orthotopic ovarian transplant--review and three surgical techniques.
AB  - Transplantation of organs is a rapidly expanding faculty of medicine. While the
      solid organ transplantation has grown by leaps and bounds, ovarian
      transplantation is still in its infancy. Although recent interest has been
      generated for preservation of fertility in cancer therapy patients, other
      indications have emerged. Ovarian dysgenesis with missing normal ovarian
      complement and premature ovarian failure has come in the forefront. Three cases
      of orthotopic ovarian transplant with different surgical techniques have been
      described along with a brief overview.

PMID- 17032424
TI  - Outcome after kidney transplantation in children with thrombotic risk factors.
AB  - BACKGROUND: According to the data from the North American Pediatric Renal
      Transplant Cooperative Study (NAPRTCS), vascular thrombosis accounts for 11.6% of
      graft losses in pediatric renal transplantation. In adults, inherited and
      acquired thrombophilic risk factors, e.g. factor V Leiden mutation, have been
      associated with early graft loss and increased rejection episodes. Data on the
      impact of these factors on the outcome of children after renal transplantation
      are rare. METHODS/PATIENTS: Sixty-six pediatric patients awaiting renal
      transplantation (mean age 10.1 yr) were screened for inherited and acquired risk
      factors for hypercoagulable disorders (protein C, S, and antithrombin III
      deficiency, antiphospholipid antibodies, factor V Leiden, prothrombin, and MTHFR
      mutation) in order to intensify anticoagulation in those with an increased risk
      for thrombophilia: intravenous heparin was administered with a partial
      prothrombin time (PTT) prolongation of 50 s for 14 days and switched to low
      molecular-weight heparin for another 8 wk before aspirin was introduced for the
      first year. Patients without hypercoagulable risk factors were treated with
      heparin without PTT prolongation for 14 days and switched to aspirin immediately
      afterwards. The results on graft survival, incidence of acute rejection episodes,
      and long-term renal graft function were analyzed between recipients with and
      without hypercoagulable risk factors. RESULTS: Thrombophilic risk factors were
      identified in 27.3% of our patients. No thrombosis occurred. One serious bleeding
      complication led to a second surgical intervention. The rate of acute rejection
      episodes was not increased in patients with and without thrombotic risk factors
      after 90 days (16.7 vs. 25%), 1 yr (22.2 vs. 33.3%), and 3 yr (38.9 vs. 41.7%) of
      follow-up, respectively (p = n.s.). After a mean follow-up of 3 yr the kidney
      function was comparable in both groups, with 63.1 in recipients with and 69.8
      mL/min/1.73 m(2) in recipients without hypercoagulable risk (p = n.s.). At latest
      follow-up, three graft losses were found not to be attributed to thrombotic risk
      factors. INTERPRETATION: Children with thrombophilic risk factors were identified
      and treated with an intensified anticoagulation regimen after renal
      transplantation. An increased risk for graft failure, acute rejection episodes,
      or impaired renal function for pediatric renal transplant recipients with
      hypercoagulable status was not found.

PMID- 17032425
TI  - Antibodies to 60, 65 and 70 kDa heat shock proteins in pediatric allogeneic stem
      cell transplant recipients.
AB  - Allogeneic SCT remains the only means of cure for many patients with various
      malignant disorders as well as non-malignant diseases. Infection together with
      severe aGvHD may result in a significant incidence of transplant-related
      morbidity and mortality. Current evidence suggests that hSPS represent major
      immunodominant antigens in many pathogens and therefore might play an important
      role in the pathogenesis of GvHD. We investigated the levels of total Ig, IgG and
      IgM isotype antibodies to rh-hsp60, recombinant Mycobacterium bovis hsp65 and
      stress-inducible rh-hsp70 in sera of pediatric patients undergoing SCT by using
      ELISA. We studied whether humoral immune responses to hSPS follow transplant
      related complications, bacterial and fungal infection. Anti-hsp antibodies were
      detected in patients' sera before conditioning, over the course of conditioning
      and all the time post-transplant. We found no correlation between anti-hsp
      antibodies and the occurrence and severity of GvHD and/or other transplant
      related complications like graft failure, hemorrhagic cystitis and capillary
      leakage syndrome. However, elevated anti-hsp antibodies involving IgM and IgG
      isotypes were found to be associated with bacterial and fungal infection
      depending on etiological agents. We demonstrated de novo humoral response to hSPS
      in a cohort of patients with actual infection caused by Klebsiella pneumoniae
      (anti-hsp60, anti-hsp65 and anti-hsp70), Pseudomonas aeruginosa (anti-hsp60, anti
      hsp70) and Aspergillus fumigatus (anti-hsp65). We conclude that anti-hsp
      antibodies might be produced after SCT in relation to infection depending on
      etiological agents; however, transplant-related complications by themselves had a
      little impact.

PMID- 17032426
TI  - Five years' experience with thymoglobulin induction in a pediatric renal
      transplant population.
AB  - Antibody induction therapy is used in the majority of pediatric patients
      undergoing renal transplantation. Our center has previously reported short-term
      outcomes with TMG as induction therapy. We now present our experience over the
      last five yr. Patients received TMG intra- and post-operatively at a dose of 1.5
      mg/kg/day. The dose was decreased to 0.75 mg/kg/day or held dependent on the
      patient's WBC and platelet counts. Post-transplant immunosuppression also
      included corticosteroids, MMF, and either TAC or CSA. Patient and graft survival,
      number of acute rejection episodes, creatinine clearance, incidence and type of
      infections, and trough levels of calcineurin inhibitor drugs were monitored
      during the follow-up period. Thirty-four renal transplants were performed in 33
      pediatric patients ranging in age from 1.7 to 17.8 yr. Seventeen rejection
      episodes occurred during the time of follow-up with three patients having more
      than one episode, but only three episodes occurred within the first year after
      transplantation. Three patients had graft loss in the first week after
      transplantation from primary non-function (1) or technical failure/thrombosis
      (2). Graft losses occurred in seven additional patients during the time of follow
      up with the first loss occurring at 17.7 months. Among patients with functional
      grafts at one wk after transplant, graft survival at one and three yr was 100%
      and 73% respectively. There were no patient deaths. There were no cases of post
      transplant lymphoproliferative disease or other malignancy. One patient had
      symptomatic CMV disease. TMG is safe and effective as induction therapy in
      pediatric renal transplant patients. Late graft loss remains a challenge in the
      pediatric patient population, particularly in adolescents.

PMID- 17032427
TI  - Left ventricular hypertrophy in pediatric kidney transplant recipients: long-term
      follow-up study.
AB  - Cross-sectional studies indicate that LVH, known cardiovascular risk factor, is
      frequent in pediatric patients post-kidney transplant. We performed a
      retrospective longitudinal analysis of echocardiographic data collected in
      children and adolescents who received kidney transplant from 1998 to 2003. The
      first echo was performed at a median time post-transplant of 14 months in 47
      children; a second echo (echo 2) was carried out at a median time of 33 months in
      31 and a third echo (echo 3) was performed at a median time of 49 months in 14
      children. LVH was defined as LV mass index >/=95th percentile for children. LVH
      was present in echo 1 in 25 (54%) subjects. Systolic blood pressure (p = 0.02)
      and BMI (p = 0.02) independently predicted the LVH seen in echo1 in multivariate
      logistic regression. In 14 subjects with three consecutive echocardiograms LVM
      index significantly decreased from echo 1 to echo 2 and from echo 1 to echo3 (p <
      0.05), but no significant changes were observed between echo 2 and echo 3. The
      overall prevalence of LVH remained unchanged but its severity significantly
      decreased during the follow-up. The results of the study suggest that despite
      regression of LVM index overtime-pediatric patients post-kidney transplant are at
      continuous risk for developing cardiovascular disease.

PMID- 17032428
TI  - Rabbit antithymocyte globulin related decrease in platelet count reduced risk of
      pediatric renal transplant graft thrombosis.
AB  - Graft thrombosis is a serious complication in pediatric renal transplantation. We
      assess a potential protective effect for the decrease in platelet count
      associated with RATG therapy against pediatric renal transplant graft vascular
      thrombosis. Between January 1986 and December 1998, 120 kidney transplants were
      performed in 95 pediatric recipients. Patients were divided into two groups.
      Group 1 (n = 61), non-RATG group received cyclosporine, azathioprine and
      steroids, while group 2 (n = 59), RATG group, received in addition, RATG at day 1
      and continued for 4-10 days postoperatively. Platelet count prior to transplant,
      median change in absolute platelet count at 1 and 3 days post-transplant was
      recorded. Graft thrombosis incidence was examined. Six grafts (5%) developed
      thrombosis. All were in group 1 (p = 0.028). Median pretransplant platelet count
      (x10(9)/L) in group 1 was 283 vs. 280 in group 2 (p = 0.921). Median decrease in
      absolute platelet count (x10(9)/L) from pretransplant levels at one and three
      days post-transplant for group 1 and 2 was 18 vs. 83 (p </= 0.001) and 39 vs. 105
      (p </= 0.001), respectively. Graft thrombosis risk factors were similar in both
      groups. RATG use was statistically significant (p = 0.044) for reduced risk of
      graft thrombosis in multivariate analysis. Patients receiving RATG showed
      significant decrease in both platelet count and graft thrombosis incidence. A
      role for RATG related effect on platelet count is assumed.

PMID- 17032429
TI  - Rapid progression of metastatic osteosarcoma after initiation of a reduced
      intensity conditioning regimen with immunosuppressive fludarabine.
AB  - Indications for RIST have not been established in patients with solid tumors. In
      this study, we performed RIST as immunotherapy in a 13-yr-old girl with
      intractable but not progressive osteosarcoma, which originated from the inter
      costal region. Carcinomatous pleurisy suddenly developed after the start of a
      conditioning regimen that included Flu and BUS. She died of respiratory failure
      on day +19 without signs of engraftment. This case suggests that unexpected
      acceleration of tumor growth may occur following RIST with immunosuppressive
      drugs before the development of a beneficial GVT effect.

PMID- 17032430
TI  - Significant morbidity associated with RSV infection in immunosuppressed children
      following liver transplantation: case report and discussion regarding need of
      routine prophylaxis.
AB  - Respiratory syncytial virus (RSV) is an important cause of lower respiratory
      tract infection in infants and young children. In immunocompromised children, RSV
      infection poses a serious health threat with significantly increased and
      prolonged virus shedding and the development of severe respiratory disease. We
      report two patients, eight months and 20 months of age, who were admitted with
      severe RSV infection two months and 10 months post-transplant respectively. Major
      risk factors for severe infection is the degree of immunosuppression and the age
      of the patient (<24 months). Based on the significant morbidity associated with
      RSV infection in these patients, we recommend randomized trials in larger
      pediatric solid organ transplant centers to evaluate the use of palivizumab
      prophylaxis is efficacious to prevent morbidity in patients under the age of 24
      months, while we emphasize good hygienic practices to prevent RSV nosocomial
      infection.

PMID- 17032432
TI  - Obstructive jaundice caused by biliary stone formation around the stent after
      liver transplantation.
AB  - We report an unusual case of obstructive jaundice caused by a biliary stone,
      which developed in the stump of a Roux-en-Y hepaticojejunostomy after undergoing
      LT. The patient was a 13-yr-old male. At 74 days after birth, a
      hepaticojejunostomy (Kasai's procedure) was performed for the treatment of
      biliary atresia. He underwent a reduced size deceased donor LT in the left
      subphrenic space twice at the age of one and three years in Australia. Eleven
      years after his second LT, he developed liver dysfunction and jaundice with a low
      grade fever. Computed tomography showed a marked jejunal loop enlargement by a
      rugby ball-shaped stone and the bile duct in the graft was thus dilated. A
      surgical exploration revealed the jejunal loop to be bent sharply while its stump
      side was dilated by stagnated bile including a biliary stone. The stone included
      a stent that had been previously used for the hepaticojejunostomy. This case
      suggests that a retained stent used for hepaticojejunostomy had thus caused
      biliary stone formation because of a combination of various conditions in the
      jejunal loop.

PMID- 17032431
TI  - Autologous hematopoietic stem cell transplant with melphalan and thiotepa is safe
      and feasible in pediatric patients with low normalized glomerular filtration
      rate.
AB  - Normalized glomerular filtration rate (nGFR) <60 mL/min/1.73 m(2) often precludes
      hematopoietic stem cell transplant (HSCT) in pediatric patients. Three patients
      with nGFR < 60 mL/min/1.73 m(2) enrolled on an institutional phase I trial of
      HSCT preparative therapy for advanced and recurrent solid tumors with escalating
      melphalan, ranging from 135 to 180 mg/m(2), thiotepa (600 mg/m(2)), and
      vincristine (2 mg/m(2)). An additional patient with low nGFR was treated with the
      same preparative therapy. None of the patients developed acute renal failure,
      excess toxicities during HSCT or delayed engraftment. These cases demonstrate
      that it is feasible and safe to perform HSCT in pediatric patients with low nGFR
      using melphalan- and thiotepa-based preparative therapy.

PMID- 17032433
TI  - Emerging viral infections in transplantation.
AB  - Viral infections are an important complication of transplantation. The
      introduction of more potent immunosuppressive agents over the past decade
      correlates with an increase in the rate of hospitalizations of transplant
      patients with infections. Specifically, viral infections have emerged as a major
      source of morbidity and mortality in transplantation. There are several potential
      intervention strategies in the face of emerging infections and it is likely that
      the approach will differ depending on the virus in question. These include viral
      surveillance and pre-emptive therapy, intervention of the transplant community,
      and policy change at the level of government, blood bank and organ procurement
      organizations. This review focuses on the emergence of the herpesviruses; HHV-6
      and HHV-7. In addition, the issue of virus transmission through organ transplant
      is addressed with a discussion of West Nile virus and the rabies virus.

PMID- 17032434
TI  - Living donor kidney transplantation in pediatric recipients.
AB  - Living donor kidney transplantation has increased in frequency in pediatric
      patients, accounting for 43% of cases performed between 1987 and 1991, and 52% of
      cases performed between 1987 and 2004 in North America. Patient survival has
      remained excellent over the years, and is currently over 96% at five years. Graft
      survival has improved over the years, and is currently over 95% at one year.
      Rejection rates have fallen over the years, and are currently <25% overall, with
      selected centers having very low rejection rates. The reasons for these improved
      outcomes are likely related to improvements in maintenance immunosuppression,
      which include a transition from cyclosporine to tacrolimus-based regimens, and
      from azathioprine to mycophenolate mofetil or sirolimus as adjunctive agents.
      Steroid withdrawal and steroid avoidance are beginning to be utilized by several
      centers, with excellent early outcomes. Finally, while there may be center
      effect/learning curve issues involved, the type of donor nephrectomy has recently
      been shown to influence early outcomes, particularly in very young recipients.

PMID- 17032435
TI  - Should children ever be living kidney donors?
AB  - Living kidney donation by minors is an infrequently performed although highly
      controversial procedure. This manuscript reports the frequency of this practice
      in North America, Europe, Australia and New Zealand. The relevant laws and
      professional guidelines are reviewed and the ethical considerations discussed.

PMID- 17032436
TI  - Polyoma virus in pediatric renal transplantation.
AB  - Renal transplantation is the treatment of choice for children with end-stage
      renal disease. Patient survival and allograft survival have improved with better
      immunosuppressant regimes to reduce acute allograft rejection but post-transplant
      infections have been exacerbated. An emerging problematic virus in the past
      decade is the polyoma virus BKV. The features of BKV including the clinical
      features in the general and immune compromised population are reviewed and
      correlated with pediatric studies in the post-transplant population. These
      features are placed in context with lessons learned about BKV in relevant adult
      studies.

PMID- 17032437
TI  - Pediatric living donor lobar lung transplantation.
AB  - Living donor lobar lung transplantation (LDLLT) was developed in order to
      mitigate the growing competition for deceased donor (DD) lungs and resultant
      increase in waiting list mortality. Because each of the two donor lobes serves as
      an entire lung for the recipient, donors who are taller than the recipient are
      preferred. Therefore LDLLT is particularly well suited for pediatric recipients
      for whom adults serve as donors. Although long-term outcomes after LDLLT reported
      by the Organ Procurement and Transplantation Network (OPTN) are worse compared
      with DD recipients, overall pediatric outcomes as well as single center reports
      from the most experienced programs are more promising. Particularly encouraging
      are the findings that bronchiolitis obliterans (OB) is less frequent or less
      severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may
      be improved by careful selection of donors to ensure adequately sized donor lobes
      and minimization of infectious risks. Although no donor deaths have been
      reported, there is a moderate risk of significant short-term complications. Long
      term follow-up has not been reported. The use of LDLLT has decreased in recent
      years, and the recent change by the OPTN to an urgency/benefit allocation system
      for DD lungs in patients 12 yr and older may further reduce the demand.
      Nonetheless, we anticipate that LDLLT will continue to be utilized in select
      circumstances, particularly in children under 12 where access to DD organs
      remains challenging.

PMID- 17032438
TI  - Determination of bacteriocin activity with bioassays carried out on solid and
      liquid substrates: assessing the factor "indicator microorganism".
AB  - BACKGROUND: Successful application of growth inhibition techniques for
      quantitative determination of bacteriocins relies on the sensitivity of the
      applied indicator microorganism to the bacteriocin to which is exposed. However,
      information on indicator microorganisms' performance and comparisons in
      bacteriocin determination with bioassays is almost non-existing in the
      literature. The aim of the present work was to evaluate the parameter "indicator
      microorganism" in bioassays carried out on solid -agar diffusion assay- and
      liquid -turbidometric assay- substrates, applied in the quantification of the
      most studied bacteriocin nisin. RESULTS: The performance of characterized
      microorganisms of known sources, belonging to the genera of Lactobacillus,
      Pediococcus, Micrococcus and Leuconostoc, has been assessed in this work in the
      assays of plate agar diffusion and turbidometry. Dose responses and sensitivities
      were examined and compared over a range of assay variables in standard
      bacteriocin solutions, fermentation broth filtrates and processed food samples.
      Measurements on inhibition zones produced on agar plates were made by means of
      digital image analysis. The data produced were analyzed statistically using the
      ANOVA technique and pairwise comparisons tests. Sensitivity limits and linearity
      of responses to bacteriocin varied significantly among different test
      microorganisms in both applied methods, the lower sensitivity limits depending on
      both the test-microorganism and the applied method. In both methods, however,
      only two of the nine tested microorganisms (Lactobacillus curvatus ATCC 51436 and
      Pediococcus acidilactici ATCC 25740) were sensitive to very low concentrations of
      the bacteriocin and produced a linear-type of response in all kinds of samples
      used in this work. In all cases, very low bacteriocin concentrations, e.g. 1
      IU/ml nisin, were more accurately determined in the turbidometric assay.
      CONCLUSION: The present work shows that in growth inhibition techniques used in
      bacteriocin quantification, the choice of the indicator microorganism is
      critical. Evaluation of sensitivity levels and type of produced responses showed
      that they can vary widely among different test-microorganisms and different
      applied methods, indicating that not all microorganisms can be used successfully
      as indicators and that measurements of growth inhibition in liquid media produce
      more reliable results.

PMID- 17032439
TI  - Comparison between Long-Menu and Open-Ended Questions in computerized medical
      assessments. A randomized controlled trial.
AB  - BACKGROUND: Long-menu questions (LMQs) are viewed as an alternative method for
      answering open-ended questions (OEQs) in computerized assessment. So far this
      question type and its influence on examination scores have not been studied
      sufficiently. However, the increasing use of computerized assessments will also
      lead to an increasing use of this question type. Using a summative online key
      feature (KF) examination we evaluated whether LMQs can be compared with OEQs in
      regard to the level of difficulty, performance and response times. We also
      evaluated the content for its suitability for LMQs. METHODS: We randomized 146
      fourth year medical students into two groups. For the purpose of this study we
      created 7 peer-reviewed KF-cases with a total of 25 questions. All questions had
      the same content in both groups, but nine questions had a different answer type.
      Group A answered 9 questions with an LM type, group B with an OE type. In
      addition to the LM answer, group A could give an OE answer if the appropriate
      answer was not included in the list. RESULTS: The average number of correct
      answers for LMQs and OEQs showed no significant difference (p = 0.93). Among all
      630 LM answers only one correct term (0.32%) was not included in the list of
      answers. The response time for LMQs did not significantly differ from that of
      OEQs (p = 0.65). CONCLUSION: LMQs and OEQs do not differ significantly. Compared
      to standard multiple-choice questions (MCQs), the response time for LMQs and OEQs
      is longer. This is probably due to the fact that they require active problem
      solving skills and more practice. LMQs correspond more suitable to Short answer
      questions (SAQ) then to OEQ and should only be used when the answers can be
      clearly phrased, using only a few, precise synonyms.LMQs can decrease cueing
      effects and significantly simplify the scoring in computerized assessment.

PMID- 17032440
TI  - TreeDyn: towards dynamic graphics and annotations for analyses of trees.
AB  - BACKGROUND: Analyses of biomolecules for biodiversity, phylogeny or
      structure/function studies often use graphical tree representations. Many
      powerful tree editors are now available, but existing tree visualization tools
      make little use of meta-information related to the entities under study such as
      taxonomic descriptions or gene functions that can hardly be encoded within the
      tree itself (if using popular tree formats). Consequently, a tedious manual
      analysis and post-processing of the tree graphics are required if one needs to
      use external information for displaying or investigating trees. RESULTS: We have
      developed TreeDyn, a tool using annotations and dynamic graphical methods for
      editing and analyzing multiple trees. The main features of TreeDyn are 1) the
      management of multiple windows and multiple trees per window, 2) the export of
      graphics to several standard file formats with or without HTML encapsulation and
      a new format called TGF, which enables saving and restoring graphical analysis,
      3) the projection of texts or symbols facing leaf labels or linked to nodes,
      through manual pasting or by using annotation files, 4) the highlight of
      graphical elements after querying leaf labels (or annotations) or by selection of
      graphical elements and information extraction, 5) the highlight of targeted trees
      according to a source tree browsed by the user, 6) powerful scripts for
      automating repetitive graphical tasks, 7) a command line interpreter enabling the
      use of TreeDyn through CGI scripts for online building of trees, 8) the inclusion
      of a library of packages dedicated to specific research fields involving trees.
      CONCLUSION: TreeDyn is a tree visualization and annotation tool which includes
      tools for tree manipulation and annotation and uses meta-information through
      dynamic graphical operators or scripting to help analyses and annotations of
      single trees or tree collections.

PMID- 17032441
TI  - A graph-search framework for associating gene identifiers with documents.
AB  - BACKGROUND: One step in the model organism database curation process is to find,
      for each article, the identifier of every gene discussed in the article. We
      consider a relaxation of this problem suitable for semi-automated systems, in
      which each article is associated with a ranked list of possible gene identifiers,
      and experimentally compare methods for solving this geneId ranking problem. In
      addition to baseline approaches based on combining named entity recognition (NER)
      systems with a "soft dictionary" of gene synonyms, we evaluate a graph-based
      method which combines the outputs of multiple NER systems, as well as other
      sources of information, and a learning method for reranking the output of the
      graph-based method. RESULTS: We show that named entity recognition (NER) systems
      with similar F-measure performance can have significantly different performance
      when used with a soft dictionary for geneId-ranking. The graph-based approach can
      outperform any of its component NER systems, even without learning, and learning
      can further improve the performance of the graph-based ranking approach.
      CONCLUSION: The utility of a named entity recognition (NER) system for geneId
      finding may not be accurately predicted by its entity-level F1 performance, the
      most common performance measure. GeneId-ranking systems are best implemented by
      combining several NER systems. With appropriate combination methods, usefully
      accurate geneId-ranking systems can be constructed based on easily-available
      resources, without resorting to problem-specific, engineered components.

PMID- 17032442
TI  - Molecular characterisation of Mycobacterium tuberculosis isolates in the First
      National Survey of Anti-tuberculosis Drug Resistance from Venezuela.
AB  - BACKGROUND: Molecular typing of Mycobacterium tuberculosis strains has become a
      valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of
      outbreaks, tracking of epidemics, identification of genotypes and transmission
      events among patients who would have remained undetected by conventional contact
      investigation. This is the first genetic biodiversity study of M. tuberculosis in
      Venezuela. Thus, we investigated the genetic patterns of strains isolated in the
      first survey of anti-tuberculosis drug-resistance realised as part of the Global
      Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). RESULTS:
      Clinical isolates (670/873) were genotyped by spoligotyping. The results were
      compared with the international spoligotyping database (SpolDB4). Multidrug
      resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and
      resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped
      82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs)
      specific to Venezuela were identified. Eight new inter-regional clusters were
      created. The Beijing genotype was not found. The genetic network shows that the
      Latin American and Mediterranean family constitutes the backbone of the genetic
      TB population-structure in Venezuela, responsible of >60% of total TB cases
      studied. MDR was 0.5% in never treated patients and 13.5% in previously treated
      patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of
      the MDR strains, respectively. Two clusters were found to be identical by the
      four different analysis methods, presumably representing cases of recent
      transmission of MDR tuberculosis. CONCLUSION: This study gives a first overview
      of the M. tuberculosis strains circulating in Venezuela during the first survey
      of anti-tuberculosis drug-resistance. It may aid in the creation of a national
      database that will be a valuable support for further studies.

PMID- 17032443
TI  - Dobutamine reverses the vasopressin-associated impairment in cardiac index and
      systemic oxygen supply in ovine endotoxemia.
AB  - INTRODUCTION: Arginine vasopressin (AVP) is increasingly used to treat sepsis
      related vasodilation and to decrease catecholamine requirements. However, AVP
      infusion may be associated with a marked decrease in systemic blood flow and
      oxygen transport. The purpose of the present study was to evaluate whether
      dobutamine may be titrated to reverse the AVP-related decrease in cardiac index
      (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine
      endotoxemia. METHODS: Twenty-four adult ewes were chronically instrumented to
      determine cardiopulmonary hemodynamics and global oxygen transport. All ewes
      received a continuous endotoxin infusion that contributed to a hypotensive
      hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia,
      the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were
      randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the
      vehicle (normal saline; n = 6) and compared with a third group treated with AVP
      infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2
      microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60
      minutes, respectively. RESULTS: AVP infusion increased mean arterial pressure
      (MAP) and systemic vascular resistance index at the expense of a markedly
      decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68
      versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5
      +/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose
      dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/-
      0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2
      (72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1
      min-1 versus AVP group) and further increased MAP. CONCLUSION: This study
      provides evidence that dobutamine is a useful agent for reversing the AVP
      associated impairment in systemic blood flow and global oxygen transport.

PMID- 17032444
TI  - The relationship between facial skeletal class and expert-rated interpersonal
      skill: an epidemiological survey on young Italian adults.
AB  - BACKGROUND: The facial region plays a major role in determining physical
      attractiveness, so we assessed the hypothesis that the capability of successfully
      managing interpersonal relationships in young adults might be related to the
      facial skeletal class. METHODS: 1,014 young subjects applying to the Military
      Academy of Pozzuoli, Italy, were enrolled and the cephalometric evaluation was
      performed by calculating the angular relationships between skeletal points
      localized by the lateral cephalogram of the face, sorting the subjects in three
      groups corresponding to each major facial skeletal class. Concurrently, the
      subjects were evaluated by a team of psychiatrists administering the MMPI-2 test
      followed by a brief colloquium with each candidate, in order to identify those
      subjects characterized by low skills for managing interpersonal relationships.
      RESULTS: According to the psychiatric evaluation about 20% of the subjects were
      considered potentially unable to manage successfully interpersonal relationships
      (NS). Males displayed an about two-fold increased risk of being NS. No
      differences were shown in the distribution of the NS male subjects among the
      three different facial skeletal classes. On the other hand, NS females displayed
      a different distribution among the three facial skeletal classes, with a trend of
      about two-fold and four-fold, respectively, for those subjects belonging to
      classes II and III, respect to those belonging to class I. CONCLUSION: Females
      may be more sensitive to physical factors determining beauty, such as the facial
      morphology certainly is. This finding appears to be interesting especially when
      thinking about possible orthodontic interventions, although further study is
      certainly needed to confirm these results.

PMID- 17032445
TI  - Foetal and neonatal alloimmune thrombocytopaenia.
AB  - Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal
      alloimmunisation against foetal platelet antigens inherited from the father and
      different from those present in the mother, and usually presents as a severe
      isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been
      estimated at 1/800 to 1/1000 live births. NAIT has been considered to be the
      platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD,
      NAIT can occur during a first pregnancy. The spectrum of the disease may range
      from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the
      neonatal period. Mildly affected infants may be asymptomatic. In those with
      severe thrombocytopaenia, the most common presentations are petechiae, purpura or
      cephalohaematoma at birth, associated with major risk of intracranial haemorrhage
      (up to 20% of reported cases), which leads to death or neurological sequelae.
      Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed
      after birth. Once suspected, the diagnosis is confirmed by demonstration of
      maternal antiplatelet alloantibodies directed against a paternal antigen
      inherited by the foetus/neonate. Post-natal management involves transfusion of
      platelets devoid of this antigen, and should not be delayed by biological
      confirmation of the diagnosis (once the diagnosis is suspected), especially in
      case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to
      reduce the chances of death and disability due to haemorrhage. Due to the high
      rate of recurrence and increased severity of the foetal thrombocytopaenia in
      successive pregnancies, antenatal therapy should be offered. However, management
      of high-risk pregnancies is still a matter of discussion.

PMID- 17032446
TI  - Triglyceride associated polymorphisms of the APOA5 gene have very different
      allele frequencies in Pune, India compared to Europeans.
AB  - BACKGROUND: The APOA5 gene variants, -1131T>C and S19W, are associated with
      altered triglyceride concentrations in studies of subjects of Caucasian and East
      Asian descent. There are few studies of these variants in South Asians. We
      investigated whether the two APOA5 variants also show similar association with
      various lipid parameters in Indian population as in the UK white subjects.
      METHODS: We genotyped 557 Indian adults from Pune, India, and 237 UK white adults
      for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and
      genotype frequency and determined their association with fasting serum
      triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate
      general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune
      Indian subjects for analysis of linkage disequilibrium with the APOA5 variants.
      RESULTS: The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune
      Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p =
      0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015).
      Patterns of linkage disequilibrium between the two variants were similar between
      the two populations and confirmed that they occur on two different haplotypes. In
      Pune Indians, the presence of -1131C allele and the 19W allele was associated
      with a 19% and 15% increase respectively in triglyceride concentrations although
      only -1131C was significant (p = 0.0003). This effect size was similar to that
      seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175
      Pune Indian subjects showed that this variant is not in appreciable linkage
      disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). CONCLUSION: This is
      the first study to look at the role of APOA5 in Asian Indian subjects that reside
      in India. The -1131C allele is more prevalent and the 19W allele is less
      prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5
      variants are associated with triglyceride levels independent of ethnicity and
      that this association is similar in magnitude in Asian Indians and Caucasians.
      The -1131C allele is present in 36% of the Pune Indian population making it a
      powerful marker for looking at the role of elevated triglycerides in important
      conditions such as pancreatitis, diabetes and coronary heart disease.

PMID- 17032447
TI  - Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in
      invasive breast carcinoma: relation to tumor phenotype and clinical outcome.
AB  - INTRODUCTION: Our aim was to study the expression pattern of tissue inhibitor of
      metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its
      clinicopathological and prognostic value as well as its relation to markers
      indicative of the tumor phenotype. METHODS: Immunohistochemistry was performed on
      paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect
      the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB
      2, topoisomerase IIalpha and Bcl-2. RESULTS: TIMP-3 protein was immunodetected in
      the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in
      situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within
      cancer cells was correlated with carcinomas of high nuclear and histological
      grade (p = 0.032 and p = 0.015, respectively), and low ER expression (p = 0.053).
      Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of
      p53 and topoIIalpha proteins (p = 0.002 and p = 0.008, respectively), whereas it
      was positively associated with Bcl-2 expression (p = 0.020). Reduced expression
      of TIMP-3 protein within cancer cells was found to have an unfavorable impact on
      disease-free survival (p = 0.052) in the entirety of the patient population, as
      well as in both subgroups of lymph-node-positive and mutant-p53-negative patients
      (p = 0.007 and p = 0.037, respectively). Stromal localization of TIMP-3 protein
      was found to have no clinicopathological or prognostic value. CONCLUSION: This is
      the first immunohistochemical study to show that TIMP-3 protein within cancer
      cells is associated with tumor phenotype. Reduced expression of TIMP-3 protein
      within cancer cells was found to correlate with an aggressive tumor phenotype,
      negatively affecting the disease-free survival of both subgroups of lymph node
      positive and mutant-p53-negative patients.

PMID- 17032448
TI  - Spatial confidentiality and GIS: re-engineering mortality locations from
      published maps about Hurricane Katrina.
AB  - BACKGROUND: Geographic Information Systems (GIS) can provide valuable insight
      into patterns of human activity. Online spatial display applications, such as
      Google Earth, can democratise this information by disseminating it to the general
      public. Although this is a generally positive advance for society, there is a
      legitimate concern involving the disclosure of confidential information through
      spatial display. Although guidelines exist for aggregated data, little has been
      written concerning the display of point level information. The concern is that a
      map containing points representing cases of cancer or an infectious disease,
      could be re-engineered back to identify an actual residence. This risk is
      investigated using point mortality locations from Hurricane Katrina re-engineered
      from a map published in the Baton Rouge Advocate newspaper, and a field team
      validating these residences using search and rescue building markings. RESULTS:
      We show that the residence of an individual, visualized as a generalized point
      covering approximately one and half city blocks on a map, can be re-engineered
      back to identify the actual house location, or at least a close neighbour, even
      if the map contains little spatial reference information. The degree of re
      engineering success is also shown to depend on the urban characteristic of the
      neighborhood. CONCLUSION: The results in this paper suggest a need to re-evaluate
      current guidelines for the display of point (address level) data. Examples of
      other point maps displaying health data extracted from the academic literature
      are presented where a similar re-engineering approach might cause concern with
      respect to violating confidentiality. More research is also needed into the role
      urban structure plays in the accuracy of re-engineering. We suggest that health
      and spatial scientists should be proactive and suggest a series of point level
      spatial confidentiality guidelines before governmental decisions are made which
      may be reactionary toward the threat of revealing confidential information,
      thereby imposing draconian limits on research using a GIS.

PMID- 17032449
TI  - Analysis of normal and osteoarthritic canine cartilage mRNA expression by
      quantitative polymerase chain reaction.
AB  - The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised
      that the expression of selected proteases, matrix molecules, and collagens
      believed to have a role in the pathogenesis of OA would be changed in naturally
      occurring canine OA cartilage when compared to normal articular cartilage.
      Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays
      were designed measuring the expression of selected matrix molecules (collagens
      and small leucine-rich proteoglycans), key mediators of the proteolytic
      degradation of articular cartilage (metalloproteinases, cathepsins), and their
      inhibitors (tissue inhibitors of matrix metalloproteinases). All data were
      normalised using a geometric mean of three housekeeping genes, and the results
      subjected to power calculations and corrections for multiple hypothesis testing.
      We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1,
      CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA.
      The expression of TIMP2 and TIMP4 was significantly reduced in canine OA
      cartilage. The patterns of gene expression change observed in naturally occurring
      canine OA were similar to those reported in naturally occurring human OA and
      experimental canine OA. We conclude that the expression profiles of matrix
      associated molecules in end-stage mammalian OA may be comparable but that the
      precise aetiologies of OA affecting specific joints in different species are
      presently unknown.

PMID- 17032450
TI  - Traditional medicinal plant use in Loja province, Southern Ecuador.
AB  - This paper examines the traditional use of medicinal plants in Loja province,
      Southern Ecuador.Two hundred fifteen plant species were collected, identified and
      their vernacular names and traditional uses recorded. This number of species
      indicates that the healers, market vendors and members of the public interviewed
      still have a very high knowledge of plants in their surroundings, which can be
      seen as a reflection of the knowledge of the population in general. However, the
      area represents only an outlier of the larger Northern Peruvian cultural area,
      where more than 500 species of plants are used medicinally, indicating that in
      Ecuador much of the original plant knowledge has already been lost.Most plant
      species registered are only used medicinally, and only a few species have any
      other use (construction, fodder, food). The highest number of species is used for
      the treatment of "magical" (psychosomatic) ailments (39 species), followed by
      respiratory disorders (34), problems of the urinary tract (28), Fever/Malaria
      (25), Rheumatism (23) and nervous system problems (20).

PMID- 17032451
TI  - The development of the larval nervous system, musculature and ciliary bands of
      Pomatoceros lamarckii (Annelida): heterochrony in polychaetes.
AB  - BACKGROUND: To understand the evolution of animals it is essential to have taxon
      sampling across a representative spread of the animal kingdom. With the recent
      rearrangement of most of the Bilateria into three major clades (Ecdysozoa,
      Lophotrochozoa and Deuterostomia) it has become clear that the Lophotrochozoa are
      relatively poorly represented in our knowledge of animal development, compared to
      the Ecdysozoa and Deuterostomia. We aim to contribute towards redressing this
      balance with data on the development of the muscular, nervous and ciliary systems
      of the annelid Pomatoceros lamarckii (Serpulidae). We compare our data with other
      lophotrochozoans. RESULTS: P. lamarckii develops locomotory and feeding
      structures that enable it to become a swimming, planktotrophic larva within 24
      hours. Formation of the trochophore includes development of a prototroch,
      metatroch and neurotroch, development of apical and posterior nervous elements at
      similar times, and development of musculature around the ciliary bands and
      digestive tract prior to development of any body wall muscles. The adult nervous
      and muscular systems are essentially preformed in the late larva. Interestingly,
      the muscular systems of the larvae and juvenile worms do not include the circular
      muscles of the body wall, which are considered to be plesiomorphic for annelids,
      although the possibility that circular muscles develop after these stages cannot
      be ruled out at this point. CONCLUSION: A comparison between polychaetes shows
      variability in the timing (heterochrony) of development of body wall muscles and
      elements of the nervous system. These heterochronies are one route for evolution
      of different life history strategies, such as adaptations to feeding
      requirements.

PMID- 17032452
TI  - Exhaustive assignment of compositional bias reveals universally prevalent biased
      regions: analysis of functional associations in human and Drosophila.
AB  - BACKGROUND: Compositionally biased (CB) regions are stretches in protein
      sequences made from mainly a distinct subset of amino acid residues; such regions
      are frequently associated with a structural role in the cell, or with protein
      disorder. RESULTS: We derived a procedure for the exhaustive assignment and
      classification of CB regions, and have applied it to thirteen metazoan proteomes.
      Sequences are initially scanned for the lowest-probability subsequences (LPSs)
      for single amino-acid types; subsequently, an exhaustive search for lowest
      probability subsequences (LPSs) for multiple residue types is performed
      iteratively until convergence, to define CB region boundaries. We analysed >
      40,000 CB regions with > 20 million residues; strikingly, nine single-/double-
      residue biases are universally abundant, and are consistently highly ranked
      across both vertebrates and invertebrates. To home in subpopulations of CB
      regions of interest in human and D. melanogaster, we analysed CB region lengths,
      conservation, inferred functional categories and predicted protein disorder, and
      filtered for coiled coils and protein structures. In particular, we found that
      some of the universally abundant CB regions have significant associations to
      transcription and nuclear localization in Human and Drosophila, and are also
      predicted to be moderately or highly disordered. Focussing on Q-based biased
      regions, we found that these regions are typically only well conserved within
      mammals (appearing in 60-80% of orthologs), with shorter human transcription
      related CB regions being unconserved outside of mammals; they are also
      preferentially linked to protein domains such as the homeodomain and
      glucocorticoid-receptor DNA-binding domain. In general, only approximately 40-50%
      of residues in these human and Drosophila CB regions have predicted protein
      disorder. CONCLUSION: This data is of use for the further functional
      characterization of genes, and for structural genomics initiatives.

PMID- 17032454
TI  - Ciliated hepatic foregut cyst in a patient with renal cell carcinoma.
AB  - BACKGROUND: Ciliated hepatic foregut cyst is a rare condition almost always found
      incidentally on a computerized tomography scan or at autopsy. Rarely, portal vein
      compression can be a presenting finding. The cysts are usually unilocular and
      occur with greater frequency in males. There is a predilection for the left lobe.
      The cysts average 3 cm in size. CASE PRESENTATION: We present in this case report
      a ciliated hepatic foregut cyst found incidentally in the setting of renal
      carcinoma. The patient was a man known to have a large renal mass, assumed to be
      cancer, and a liver mass suspicious for metastatic disease. This liver mass was
      cystic and upon further analysis showed ciliated epithelial lining. We describe
      the gross and histological appearance, as well as a brief discussion of ciliated
      hepatic foregut cysts. CONCLUSION: We report the first case of a patient with
      coexisting renal cell carcinoma and a ciliated hepatic foregut cyst. While this
      may represent a coincidental finding, a possibility of a neoplastic or non
      neoplastic disorder associated with ciliated hepatic foregut cysts can not be
      completely ruled out.

PMID- 17032453
TI  - A preliminary study of mercury exposure and blood pressure in the Brazilian
      Amazon.
AB  - BACKGROUND: Fish is considered protective for coronary heart disease (CHD), but
      mercury (Hg) intake from fish may counterbalance beneficial effects. Although
      neurotoxic effects of methylmercury (MeHg) are well established, cardiovascular
      effects are still debated. The objective of the present study was to evaluate
      blood pressure in relation to Hg exposure and fish consumption among a non
      indigenous fish-eating population in the Brazilian Amazon. METHODS: The study was
      conducted among 251 persons from six communities along the Tapajos River, a major
      tributary of the Amazon. Data was obtained for socio-demographic information,
      fish consumption, height and weight to determine body mass index (BMI), systolic
      and diastolic blood pressure, and Hg concentration in hair samples. RESULTS:
      Results showed that overall, systolic and diastolic blood pressure, were
      relatively low (mean: 113.9 mmHg +/- 14.6 and 73.7 mmHg +/- 11.0). Blood pressure
      was significantly associated with hair total Hg (H-Hg), age, BMI and gender. No
      association was observed between fish consumption and blood pressure, although
      there were significant inter-community differences. Logistic regression analyses
      showed that the Odds Ratio (OR) for elevated systolic blood pressure (> or = 130
      mmHg) with H-Hg > or = 10 microg/g was 2.91 [1.26-7.28], taking into account age,
      BMI, smoking, gender and community. CONCLUSION: The findings of this preliminary
      study add further support for Hg cardiovascular toxicity.

PMID- 17032455
TI  - A simple method to combine multiple molecular biomarkers for dichotomous
      diagnostic classification.
AB  - BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the
      quest for squelching noise and wringing in information from a given set of
      biomarkers continues. Here, we suggest a statistical algorithm that--assuming
      each molecular biomarker to be a diagnostic test--enriches the diagnostic
      performance of an optimized set of independent biomarkers employing established
      statistical techniques. We validated the proposed algorithm using several
      simulation datasets in addition to four publicly available real datasets that
      compared i) subjects having cancer with those without; ii) subjects with two
      different cancers; iii) subjects with two different types of one cancer; and iv)
      subjects with same cancer resulting in differential time to metastasis. RESULTS:
      Our algorithm comprises of three steps: estimating the area under the receiver
      operating characteristic curve for each biomarker, identifying a subset of
      biomarkers using linear regression and combining the chosen biomarkers using
      linear discriminant function analysis. Combining these established statistical
      methods that are available in most statistical packages, we observed that the
      diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the
      real datasets used in the study. These estimates were comparable to or better
      than the ones previously reported using alternative methods. In a synthetic
      dataset, we also observed that all the biomarkers chosen by our algorithm were
      indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be
      used for accurate diagnosis in the setting of dichotomous classification of
      disease states.

PMID- 17032456
TI  - Comparison of vitrified and unvitrified Eocene woody tissues by TMAH
      thermochemolysis - implications for the early stages of the formation of
      vitrinite.
AB  - Samples of vitrified and unvitrified Eocene woody plant tissues collected from
      the Fossil Forest site, Geodetic Hills, Axel Heiberg Island, have been
      characterized by TMAH thermochemolysis. All samples are gymnosperm-derived, are
      of very low maturity and all share the same post-depositional geologic history.
      Differences in the distributions of products observed from vitrified and
      unvitrified samples suggest that vitrification of woody tissue is associated with
      modification of the lignin C3 side chain, following loss of all or most of the
      carbohydrate present in the precursor woody tissues. The key driver of
      vitrification appears to be physical compression of the tissue following
      biological removal of cellulosic materials.

PMID- 17032457
TI  - GOLEM: an interactive graph-based gene-ontology navigation and analysis tool.
AB  - BACKGROUND: The Gene Ontology has become an extremely useful tool for the
      analysis of genomic data and structuring of biological knowledge. Several
      excellent software tools for navigating the gene ontology have been developed.
      However, no existing system provides an interactively expandable graph-based view
      of the gene ontology hierarchy. Furthermore, most existing tools are web-based or
      require an Internet connection, will not load local annotations files, and
      provide either analysis or visualization functionality, but not both. RESULTS: To
      address the above limitations, we have developed GOLEM (Gene Ontology Local
      Exploration Map), a visualization and analysis tool for focused exploration of
      the gene ontology graph. GOLEM allows the user to dynamically expand and focus
      the local graph structure of the gene ontology hierarchy in the neighborhood of
      any chosen term. It also supports rapid analysis of an input list of genes to
      find enriched gene ontology terms. The GOLEM application permits the user either
      to utilize local gene ontology and annotations files in the absence of an
      Internet connection, or to access the most recent ontology and annotation
      information from the gene ontology webpage. GOLEM supports global and organism
      specific searches by gene ontology term name, gene ontology id and gene name.
      CONCLUSION: GOLEM is a useful software tool for biologists interested in
      visualizing the local directed acyclic graph structure of the gene ontology
      hierarchy and searching for gene ontology terms enriched in genes of interest. It
      is freely available both as an application and as an applet at
      http://function.princeton.edu/GOLEM.

PMID- 17032458
TI  - A case-control study of mastitis: nasal carriage of Staphylococcus aureus.
AB  - BACKGROUND: Mastitis is a common problem for breastfeeding women. Researchers
      have called for an investigation into the possible role of maternal nasal
      carriage of S. aureus in the causation of mastitis in breastfeeding women.
      METHODS: The aim of the study was to investigate the role of maternal S. aureus
      nasal carriage in mastitis. Other factors such as infant nasal S. aureus
      carriage, nipple damage, maternal fatigue and oversupply of milk were also
      investigated. A case-control design was used. Women with mastitis (cases, n =
      100) were recruited from two maternity hospitals in Melbourne, Australia
      (emergency departments, breastfeeding clinics and postnatal wards). Breastfeeding
      women without mastitis (controls, n = 99) were recruited from maternal and child
      health (community) centres and the rooms of a private obstetrician. Women
      completed a questionnaire and nasal specimens were collected from mother and baby
      and placed in charcoal transport medium. Women also collected a small sample of
      milk in a sterile jar. RESULTS: There was no difference between nasal carriage of
      S. aureus in breastfeeding women with mastitis (42/98, 43%) and control women
      (45/98, 46%). However, significantly more infants of mothers with mastitis were
      nasal carriers of S. aureus (72/88, 82%) than controls (52/93, 56%). The
      association was strong (adjusted OR 3.23, 95%CI 1.30, 8.27) after adjustment for
      the following confounding factors: income, private health insurance, difficulty
      with breastfeeding, nipple damage and tight bra. There was also a strong
      association between nipple damage and mastitis (adjusted OR 9.34, 95%CI 2.99,
      29.20). CONCLUSION: We found no association between maternal nasal carriage of S.
      aureus and mastitis, but nasal carriage in the infant was associated with breast
      infections. As in other studies of mastitis, we found a strong association
      between nipple damage and mastitis. Prevention of nipple damage is likely to
      reduce the incidence of infectious mastitis. Mothers need good advice about
      optimal attachment of the baby to the breast and access to skilled help in the
      early postpartum days and weeks.

PMID- 17032459
TI  - Proximal genomic localization of STAT1 binding and regulated transcriptional
      activity.
AB  - BACKGROUND: Signal transducer and activator of transcription (STAT) proteins are
      key regulators of gene expression in response to the interferon (IFN) family of
      anti-viral and anti-microbial cytokines. We have examined the genomic
      relationship between STAT1 binding and regulated transcription using multiple
      tiling microarray and chromatin immunoprecipitation microarray (ChIP-chip)
      experiments from public repositories. RESULTS: In response to IFN-gamma, STAT1
      bound proximally to regions of the genome that exhibit regulated transcriptional
      activity. This finding was consistent between different tiling microarray
      platforms, and between different measures of transcriptional activity, including
      differential binding of RNA polymerase II, and differential mRNA transcription.
      Re-analysis of tiling microarray data from a recent study of IFN-gamma-induced
      STAT1 ChIP-chip and mRNA expression revealed that STAT1 binding is tightly
      associated with localized mRNA transcription in response to IFN-gamma. Close
      relationships were also apparent between STAT1 binding, STAT2 binding, and mRNA
      transcription in response to IFN-alpha. Furthermore, we found that sites of STAT1
      binding within the Encyclopedia of DNA Elements (ENCODE) region are precisely
      correlated with sites of either enhanced or diminished binding by the RNA
      polymerase II complex. CONCLUSION: Together, our results indicate that STAT1
      binds proximally to regions of the genome that exhibit regulated transcriptional
      activity. This finding establishes a generalized basis for the positioning of
      STAT1 binding sites within the genome, and supports a role for STAT1 in the
      direct recruitment of the RNA polymerase II complex to the promoters of IFN-gamma
      responsive genes.

PMID- 17032461
TI  - Secondary penile tumours revisited.
AB  - OBJECTIVE: To highlight the salient features of metastatic malignancies involving
      the penis, with special reference to the primary tumour sites, metastatic
      mechanisms, clinical features, differential diagnosis, treatment and prognosis.
      METHODS: A comprehensive search of the literature was performed using MEDLINE and
      EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and
      'malignant priapism' to identify reviews and case reports of secondary penile
      malignancy. A case of rare clinical presentation of metastatic penile lesion is
      presented along with the review of the literature. CONCLUSION: Secondary
      malignancy of the penis is a rare clinical entity, despite the rich
      vascularisation of this organ. The majority of metastatic lesions take their
      origin from the neighbouring genito-urinary organs, mainly prostate and bladder.
      These lesions are often associated with disseminated malignancy and hence have a
      poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or
      priapism are the main modes of clinical presentation. In most cases, only
      palliative or supportive therapy is indicated.

PMID- 17032462
TI  - Qualitative and quantitative characteristics of the extracellular DNA delivered
      to the nucleus of a living cell.
AB  - BACKGROUND: The blood plasma and other intertissue fluids usually contain a
      certain amount of DNA, getting there due to a natural cell death in the organism.
      Cells of this organism can capture the extracellular DNA, whereupon it is
      delivered to various cell compartments. It is hypothesized that the extracellular
      DNA is involved in the transfer of genetic information and its fixation in the
      genome of recipient cell. RESULTS: The existence of an active flow of
      extracellular DNA into the cell is demonstrated using human breast adenocarcinoma
      (MCF-7) cells as a recipient culture. The qualitative state of the DNA fragments
      delivered to the main cell compartments (cytoplasm and interchromosomal fraction)
      was assessed. The extracellular DNA delivered to the cell is characterized
      quantitatively. CONCLUSION: It is demonstrated that the extracellular DNA
      fragments in several minutes reach the nuclear space, where they are processed so
      that their linear size increases from about 500 bp to 10,000 bp. The amount of
      free extracellular DNA fragments simultaneously present in the nuclear space may
      reach up to 2% of the haploid genome. Using individual DNA fragments with a known
      molecular weight and sequence as an extracellular DNA, it is found that these
      fragments degrade instantly in the culture liquid in the absence of a competitor
      DNA and are delivered into the cell as degradants. When adding a sufficient
      amount of competitor DNA, the initial undegraded molecules of the DNA fragments
      with the known molecular weight and sequence are detectable both in the cytoplasm
      and nuclear space only at the zero point of experiments. The labeled precursor
      alpha-dNTP*, added to culture medium, was undetectable inside the cell in all the
      experiments.

PMID- 17032463
TI  - Host-virus interaction: a new role for microRNAs.
AB  - MicroRNAs (miRNAs) are a new class of 18-23 nucleotide long non-coding RNAs that
      play critical roles in a wide spectrum of biological processes. Recent reports
      also throw light into the role of microRNAs as critical effectors in the
      intricate host-pathogen interaction networks. Evidence suggests that both virus
      and hosts encode microRNAs. The exclusive dependence of viruses on the host
      cellular machinery for their propagation and survival also make them highly
      susceptible to the vagaries of the cellular environment like small RNA mediated
      interference. It also gives the virus an opportunity to fight and/or modulate the
      host to suite its needs. Thus the range of interactions possible through miRNA
      mRNA cross-talk at the host-pathogen interface is large. These interactions can
      be further fine-tuned in the host by changes in gene expression, mutations and
      polymorphisms. In the pathogen, the high rate of mutations adds to the complexity
      of the interaction network. Though evidence regarding microRNA mediated cross
      talk in viral infections is just emerging, it offers an immense opportunity not
      only to understand the intricacies of host-pathogen interactions, and possible
      explanations to viral tropism, latency and oncogenesis, but also to develop novel
      biomarkers and therapeutics.

PMID- 17032464
TI  - Recent advances in the bcr-abl negative chronic myeloproliferative diseases.
AB  - The chronic myeloproliferative disorders are clonal hematopoietic stem cell
      disorders of unknown etiology. In one of these (chronic myeloid leukemia), there
      is an associated pathognomonic chromosomal abnormality known as the Philadelphia
      chromosome. This leads to constitutive tyrosine kinase activity which is
      responsible for the disease and is used as a target for effective therapy. This
      review concentrates on the search in the other conditions (polycythemia vera,
      essential thrombocythemia and idiopathic mylofibrosis) for a similar biological
      marker with therapeutic potential. There is no obvious chromosomal marker in
      these conditions and yet evidence of clonality can be obtained in females by the
      use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12
      levels and raised neutrophil alkaline phosphatase scores are evidence that cells
      in these conditions have received excessive signals for proliferation, maturation
      and reduced apoptosis. The ability of erythroid colonies to grow spontaneously
      without added external erythropoietin in some cases, provided a useful marker and
      a clue to this abnormal signaling. In the past year several important discoveries
      have been made which go a long way in elucidating the involved pathways. The
      recently discovered JAK2 V617F mutation which occurs in the majority of cases of
      polycythemia vera and in about half of the cases with the two other conditions,
      enables constitutive tyrosine kinase activity without the need for ligand binding
      to hematopoietic receptors. This mutation has become the biological marker for
      these conditions and has spurred the development of a specific therapy to
      neutralize its effects. The realization that inherited mutations in the
      thrombopoietin receptor (c-Mpl) can cause a phenotype of thrombocytosis such as
      in Mpl Baltimore (K39N) and in a Japanese family with S505A, has prompted the
      search for acquired mutations in this receptor in chronic myeloproliferative
      disease. Recently, two mutations have been found; W515L and W515K. These
      mutations have been evident in patients with essential thrombocythemia and
      idiopathic myelofibrosis but not in polycythemia vera. They presumably act by
      causing constitutional, activating conformational changes in the receptor. The
      discovery of JAK2 and Mpl mutations is leading to rapid advancements in
      understanding the pathophysiology and in the treatment of these diseases.

PMID- 17032465
TI  - Extent and structure of health insurance expenditures for complementary and
      alternative medicine in Swiss primary care.
AB  - BACKGROUND: The study is part of a nationwide evaluation of complementary and
      alternative medicine (CAM) in primary care in Switzerland. The goal was to
      evaluate the extent and structure of basic health insurance expenditures for
      complementary and alternative medicine in Swiss primary care. METHODS: The study
      was designed as a cross-sectional evaluation of Swiss primary care providers and
      included 262 certified CAM physicians, 151 noncertified CAM physicians and 172
      conventional physicians. The study was based on data from a mailed questionnaire
      and on reimbursement information obtained from health insurers. It was therefore
      purely observational, without interference into diagnostic and therapeutic
      procedures applied or prescribed by physicians. Main outcome measures included
      average reimbursed costs per patient, structured into consultation- and
      medication-related costs, and referred costs. RESULTS: Total average reimbursed
      cost per patient did not differ between CAM physicians and conventional
      practitioners, but considerable differences were observed in cost structure. The
      proportions of reimbursed costs for consultation time were 56% for certified CAM,
      41% for noncertified CAM physicians and 40% for conventional physicians;
      medication costs--including expenditures for prescriptions and directly dispensed
      drugs--respectively accounted for 35%, 18%, and 51% of costs. CONCLUSION: The
      results indicate no significant difference for overall treatment cost per patient
      between CAM and COM primary care in Switzerland. However, CAM physicians treat
      lower numbers of patients and a more cost-favourable patient population than
      conventional physicians. Differences in cost structure reflect more patient
      centred and individualized treatment modalities of CAM physicians.

PMID- 17032466
TI  - Retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of
      photoreceptors and characterized by retinal pigment deposits visible on fundus
      examination. Prevalence of non syndromic RP is approximately 1/4,000. The most
      common form of RP is a rod-cone dystrophy, in which the first symptom is night
      blindness, followed by the progressive loss in the peripheral visual field in
      daylight, and eventually leading to blindness after several decades. Some extreme
      cases may have a rapid evolution over two decades or a slow progression that
      never leads to blindness. In some cases, the clinical presentation is a cone-rod
      dystrophy, in which the decrease in visual acuity predominates over the visual
      field loss. RP is usually non syndromic but there are also many syndromic forms,
      the most frequent being Usher syndrome. To date, 45 causative genes/loci have
      been identified in non syndromic RP (for the autosomal dominant, autosomal
      recessive, X-linked, and digenic forms). Clinical diagnosis is based on the
      presence of night blindness and peripheral visual field defects, lesions in the
      fundus, hypovolted electroretinogram traces, and progressive worsening of these
      signs. Molecular diagnosis can be made for some genes, but is not usually
      performed due to the tremendous genetic heterogeneity of the disease. Genetic
      counseling is always advised. Currently, there is no therapy that stops the
      evolution of the disease or restores the vision, so the visual prognosis is poor.
      The therapeutic approach is restricted to slowing down the degenerative process
      by sunlight protection and vitaminotherapy, treating the complications (cataract
      and macular edema), and helping patients to cope with the social and
      psychological impact of blindness. However, new therapeutic strategies are
      emerging from intensive research (gene therapy, neuroprotection, retinal
      prosthesis).

PMID- 17032460
TI  - Analysis of the dermatophyte Trichophyton rubrum expressed sequence tags.
AB  - BACKGROUND: Dermatophytes are the primary causative agent of dermatophytoses, a
      disease that affects billions of individuals worldwide. Trichophyton rubrum is
      the most common of the superficial fungi. Although T. rubrum is a recognized
      pathogen for humans, little is known about how its transcriptional pattern is
      related to development of the fungus and establishment of disease. It is
      therefore necessary to identify genes whose expression is relevant to growth,
      metabolism and virulence of T. rubrum. RESULTS: We generated 10 cDNA libraries
      covering nearly the entire growth phase and used them to isolate 11,085 unique
      expressed sequence tags (ESTs), including 3,816 contigs and 7,269 singletons.
      Comparisons with the GenBank non-redundant (NR) protein database revealed
      putative functions or matched homologs from other organisms for 7,764 (70%) of
      the ESTs. The remaining 3,321 (30%) of ESTs were only weakly similar or not
      similar to known sequences, suggesting that these ESTs represent novel genes.
      CONCLUSION: The present data provide a comprehensive view of fungal physiological
      processes including metabolism, sexual and asexual growth cycles, signal
      transduction and pathogenic mechanisms.

PMID- 17032468
TI  - Anthelmintic action of plant cysteine proteinases against the rodent stomach
      nematode, Protospirura muricola, in vitro and in vivo.
AB  - Cysteine proteinases from the fruit and latex of plants, including papaya,
      pineapple and fig, were previously shown to have a rapid detrimental effect, in
      vitro, against the rodent gastrointestinal nematodes, Heligmosomoides polygyrus
      (which is found in the anterior small intestine) and Trichuris muris (which
      resides in the caecum). Proteinases in the crude latex of papaya also showed
      anthelmintic efficacy against both nematodes in vivo. In this paper, we describe
      the in vitro and in vivo effects of these plant extracts against the rodent
      nematode, Protospirura muricola, which is found in the stomach. As in earlier
      work, all the plant cysteine proteinases examined, with the exception of
      actinidain from the juice of kiwi fruit, caused rapid loss of motility and
      digestion of the cuticle, leading to death of the nematode in vitro. In vivo, in
      contrast to the efficacy against H. polygyrus and T. muris, papaya latex only
      showed efficacy against P. muricola adult female worms when the stomach acidity
      had been neutralized prior to administration of papaya latex. Therefore,
      collectively, our studies have demonstrated that, with the appropriate
      formulation, plant cysteine proteinases have efficacy against nematodes residing
      throughout the rodent gastrointestinal tract.

PMID- 17032467
TI  - Domestic dogs and cats as sources of Trypanosoma cruzi infection in rural
      northwestern Argentina.
AB  - The reservoir capacity of domestic cats and dogs for Trypanosoma cruzi infection
      and the host-feeding patterns of domestic Triatoma infestans were assessed
      longitudinally in 2 infested rural villages in north-western Argentina. A total
      of 86 dogs and 38 cats was repeatedly examined for T. cruzi infection by serology
      and/or xenodiagnosis. The composite prevalence of infection in dogs (60%), but
      not in cats, increased significantly with age and with the domiciliary density of
      infected T. infestans. Dogs and cats had similarly high forces of infection,
      prevalence of infectious hosts (41-42%), and infectiousness to bugs at a wide
      range of infected bug densities. The infectiousness to bugs of seropositive dogs
      declined significantly with increasing dog age and was highly aggregated.
      Individual dog infectiousness to bugs was significantly autocorrelated over time.
      Domestic T. infestans fed on dogs showed higher infection prevalence (49%) than
      those fed on cats (39%), humans (38%) or chickens (29%) among 1085 bugs examined.
      The basic reproduction number of T. cruzi in dogs was at least 8.2. Both cats and
      dogs are epidemiologically important sources of infection for bugs and
      householders, dogs nearly 3 times more than cats.

PMID- 17032469
TI  - The use of chicory for parasite control in organic ewes and their lambs.
AB  - The aim of the present study was to investigate the potential benefits of grazing
      lactating ewes and their lambs on chicory (Cichorium intybus). Fifty-six
      certified organic twin-rearing ewes were either drenched with an anthelmintic or
      not, within 2 days after parturition and were grazed upon either grass/clover or
      chicory pastures. Around 12 weeks after parturition a subset of 12 lambs per
      treatment was slaughtered for worm number and parasite species determination. The
      faecal egg counts of lambs from undrenched ewes grazing on chicory were
      significantly lower than those of lambs from undrenched ewes grazing on grass.
      Lambs grazing on chicory had similar abomasal worm counts as those grazing on
      grass at 12 weeks of age; the predominant species was Teladorsagia circumcincta.
      There was no difference between the intestinal worm counts in lambs grazing on
      grass or chicory, with Trichostrongylus vitrinus being the predominant species.
      Liveweight gains over the 126-day experimental period were significantly higher
      in lambs from drenched than those from undrenched ewes. Lambs from undrenched
      ewes grazing on chicory had higher liveweight gains compared to those from
      undrenched ewes grazing on grass. Although chicory grazing did not affect ewe
      nematode egg excretion, it resulted in lower egg counts in lambs and improved
      their liveweight gains to the same level as those deriving from drenched ewes.

PMID- 17032470
TI  - Proteomic analysis of Entamoeba histolytica.
AB  - In this study, the proteome of axenically grown Entamoeba histolytica parasites
      was explored by two-dimensional gel electrophoresis (2-DE), employing a practical
      and effective procedure for the solubilization of E. histolytica proteins.
      Approximately 900 protein species in the pH range between 4 and 7 were detected
      by Coomassie Blue staining. Ninety-five spots were excised, trypsinated and
      subjected to mass spectrometry. The resultant data from peptide mass fingerprints
      were compared with those available in the E. histolytica genome and the (non
      redundant) National Center for Biotechnology Information (NCBI) databases for the
      identification and categorization of proteins. Sixty-three of the proteins
      identified were predicted to relate to the cytoskeleton, surface, glycolysis,
      RNA/DNA metabolism, the ubiquitin-proteasome system, vesicular trafficking and
      signal transduction. The present study demonstrates, for the first time, that
      corresponding genes are indeed expressed in E. histolytica and provides a
      foundation for further proteomic studies of this parasite.

PMID- 17032471
TI  - Antiparasitic effect of calcium and magnesium ion-free buffer treatments against
      a common monogenean Neobenedenia girellae.
AB  - This study investigated a new effective method for controlling the capsalid
      monogenean Neobenedenia girellae. We examined in vitro and in vivo the effect on
      the percentage survival of N. girellae in buffers containing different metallic
      ions. Decreased survival was observed in buffer solutions lacking two ions. In
      particular, the percentage survival of N. girellae was significantly decreased
      after 10 min exposure to buffer containing neither Ca(2+) nor Mg(2+).
      Transmission electron microscopic observations showed that treatment with this
      buffer disrupted intercellular junctions. This significant effect on percentage
      survival of N. girellae using Ca(2+)/Mg(2+)-free buffer was confirmed in an in
      vivo assay. Ca(2+)/Mg(2+)-free buffer had no effect on the condition of the host,
      spotted halibut Verasper variegates (Pleuronectidae). These results suggest that
      treatment with Ca(2+)/Mg(2+)-free buffer is a new effective control method, which
      could replace existing control methods.

PMID- 17032472
TI  - The effect of inulin on new and on patent infections of Trichuris suis in growing
      pigs.
AB  - The objective of this experiment was to investigate the potential influence of
      inulin on the establishment of new and patent infections of Trichuris suis in
      growing pigs. Two experimental diets were formulated based on barley flour with
      either added insoluble fibre from oat husk (Diet 1) or a pure inulin (16%)
      supplementation (Diet 2). Twenty-eight 10-week-old pigs were divided randomly
      into 4 groups (Groups 1-4) each of 7 pigs. After 3 weeks adaptation to the
      experimental diets all pigs were infected with a single dose of 2000 infective T.
      suis eggs. Group 1 was fed Diet 1 until 7 weeks post-infection (p.i.) and Group 3
      until 9 weeks p.i., Group 2 was fed Diet 2 until 7 weeks p.i., Group 4 was fed
      Diet 1 until week 7 p.i. and was switched-over from Diet 1 to Diet 2 until week 9
      p.i. Seven weeks p.i. pigs in Groups 1 and 2 were slaughtered, and pigs in Groups
      3 and 4 were slaughtered at 9 weeks p.i. Trichuris suis worm burdens were
      determined for all pigs. Inulin-fed pigs (Group 2) exhibited an 87% reduction in
      EPG, compared to the pigs on standard diet (Group 1) (P < 0.0001). The number of
      worms recovered at week 7 p.i. from pigs on the inulin diet (Group 2) was
      significantly reduced by 71%, compared to the pigs on standard diet (Group 1) (P
      < 0.01). At week 9, worm recovery in pigs on the inulin diet switch protocol
      (Group 4) was reduced by 47% compared to the control pigs in Group 3 (P < 0.01).
      Further, the inulin-fed pigs exhibited a significant reduction in female worm
      fecundity and worm large intestine location was more distal compared to those
      from pigs on standard diet. These results demonstrate that inclusion of the
      highly degradable fructose polymer inulin in the diet leads to significant
      reductions in T. suis establishment, egg excretion, and female worm fecundity and
      can be used as a treatment for patent infections.

PMID- 17032473
TI  - Composition and diversity patterns in metazoan parasite communities and
      anthropogenic disturbance in stream ecosystems.
AB  - The composition and diversity of metazoan parasite communities in naturally
      depauperate ecosystems are rarely studied. This study describes the composition
      of helminth endoparasite communities infecting fish that are part of naturally
      acidic stream ecosystems in the coastal-plains region of the State of New Jersey
      (USA) known as the Pinelands, and compares the diversity of parasites between six
      streams that differ in anthropogenic disturbance. A total of 514 fish were
      examined representing 6 species native but restricted to the Pinelands region, 5
      species native and widespread throughout the region and State, and 6 species
      introduced to the Pinelands and State. Fish (prevalence: 78%) were infected with
      18 helminth endoparasite species. In most streams, prevalence of infection, mean
      abundance, and total number of individuals for the 5 most common parasites were
      higher in pirate perch, a native fish species. The diversity of helminth
      endoparasite communities measured as species richness and Shannon index was
      higher in degraded streams, and especially in native or introduced fish at these
      sites. Parasite diversity was positively correlated with anthropogenic
      disturbance, which was measured by water pH, water conductance, and the
      proportion of agricultural and developed land surrounding streams. Helminth
      community composition included parasites intimately tied to trophic interactions
      in food webs, and disturbance to these ecosystems results in changes to these
      communities. Understanding structure and function of animal communities from
      these naturally depauperate ecosystems is important before continued
      anthropogenic changes result in the extirpation or extinction of their unique
      fauna.

PMID- 17032474
TI  - Evidence of an altered protective effect of metallothioneins after cadmium
      exposure in the digenean parasite-infected cockle (Cerastoderma edule).
AB  - The aim of the present study was to analyse the relation between parasitism and
      subsequent metallothioneins (MT) in the case of metal contamination. Experimental
      exposure of parasitized and unparasitized cockles (Cerastoderma edule) to cadmium
      (Cd) was performed, with the cockle as first or second intermediate host of 2
      digenean species. After 7 days of Cd exposure in microcosms, cockles infected as
      first intermediate host by Labratrema minimus exhibited metal concentrations in
      tissues double that in uninfected cockles. Jointly, MT concentrations of
      parasitized cockles were not modified in comparison with uninfected individuals
      in which concentrations were increased 4.3-fold compared with controls. In
      cockles experimentally infected as the second intermediate host by Himasthla
      elongata, cadmium concentrations significantly increased again in parasitized
      cockles compared with uninfected individuals in contaminated conditions.
      Simultaneously, MT concentrations in healthy cockles increased, whereas they
      significantly decreased in parasitized individuals. Therefore, the presence of
      digenean parasites in Cd-exposed cockles leads to a maintenance or a decrease in
      MT concentrations compared with healthy individuals, whereas Cd accumulation in
      tissues is significantly increased. These experiments indicate a significant
      alteration of the protective effect of metallothioneins towards metals which
      could consequently enhance cockle vulnerability. Moreover, these results
      highlight the limit of the use of MT as a biomarker of metal pollution in field
      monitoring if parasitism is not taken into account.

PMID- 17032475
TI  - Mitochondrial genomes of parasitic arthropods: implications for studies of
      population genetics and evolution.
AB  - Over 39000 species of arthropods parasitize humans, domestic animals and
      wildlife. Despite their medical, veterinary and economic importance, most aspects
      of the population genetics and evolution of the vast majority of parasitic
      arthropods are poorly understood. Mitochondrial genomes are a rich source of
      markers for studies of population genetics and evolution. These markers include
      (1) nucleotide sequences of each of the 37 mitochondrial genes and non-coding
      regions; (2) concatenated nucleotide sequences of 2 or more genes; and (3)
      genomic features, such as gene duplications, gene rearrangements, and changes in
      gene content and secondary structures of RNAs. To date, the mitochondrial genomes
      of over 700 species of multi-cellular animals have been sequenced entirely,
      however, only 24 of these species are parasitic arthropods. Of the mitochondrial
      genome markers, only the nucleotide sequences of 4 mitochondrial genes, cox1,
      cob, rrnS and rrnL, have been well explored in population genetic and
      evolutionary studies of parasitic arthropods whereas the sequences of the other
      33 genes, and various genomic features have not. We review current knowledge of
      the mitochondrial genomes of parasitic arthropods, summarize applications of
      mitochondrial genes and genomic features in population genetic and evolutionary
      studies, and highlight prospects for future research.

PMID- 17032476
TI  - Vector seasonality, host infection dynamics and fitness of pathogens transmitted
      by the tick Ixodes scapularis.
AB  - Fitness of tick-borne pathogens may be determined by the degree to which their
      infection dynamics in vertebrate hosts permits transmission cycles if infective
      and uninfected tick stages are active at different times of the year. To
      investigate this hypothesis we developed a simulation model that integrates the
      transmission pattern imposed by seasonally asynchronous nymphal and larval Ixodes
      scapularis ticks in northeastern North America, with a model of infection in
      white-footed mice (Peromyscus leucopus) reservoir hosts, using the bacteria
      Borrelia burgdorferi and Anaplasma phagocytophilum as examples. In simulations,
      survival of microparasites, their sensitivity to reduced rodent and tick
      abundance, and to 'dilution' by a reservoir-incompetent host depended on traits
      that allowed (i) highly efficient transmission from acutely-infected hosts, (ii)
      long-lived acute or 'carrier' host infections, and/or (iii) transmission amongst
      co-feeding ticks. Minimum values for transmission efficiency to ticks, and
      duration of host infectivity, necessary for microparasite persistence, were
      always higher when nymphal and larval ticks were seasonally asynchronous than
      when these instars were synchronous. Thus, traits influencing duration of host
      infectivity, transmission efficiency to ticks and co-feeding transmission are
      likely to be dominant determinants of fitness in I. scapularis-borne
      microparasites in northeastern North America due to abiotic forcings influencing
      I. scapularis seasonality.

PMID- 17032477
TI  - Differential N-glycan- and protein-directed immune responses in Dictyocaulus
      viviparus-infected and vaccinated calves.
AB  - Calves with naturally acquired Dictyocaulus viviparus infection mount an
      effective immune response. In the search for protection-inducing antigens, we
      found that several D. viviparus third-stage larval (L3) and adult ES products
      carry N-glycans. Deglycosylation of the worm antigens using PNGase F resulted in
      reduced IgA, IgE, IgG1 and IgG2 (but not IgM) reactivities in sera of primary
      infected animals, suggesting that the carbohydrate moieties contained
      immunodominant epitopes. Challenge infection resulted in increased specific serum
      antibody levels against ES and L3 in the re-infected and challenge control
      groups. Testing of sera by enzyme-linked immunosorbent assay (ELISA) demonstrated
      a significant increase in IgG1 and IgE (but not IgA or IgG2) reactivity against
      the deglycosylated antigens in the re-infected group compared with the challenge
      control group. Sera from calves vaccinated with irradiated larvae showed a strong
      anti-N-glycan response, but no booster response against the protein backbone
      after challenge infection, consistent with the absence of a memory response.
      Together, our results suggest that D. viviparus proteins carry immunodominant N
      glycan moieties that elicit a strong but short-lived immune response during
      infection and after vaccination, whereas the protein backbones effectively induce
      a memory response which results in a long-lasting, potentially protective immune
      response in re-infected, but not in vaccinated calves.

PMID- 17032478
TI  - Evaluation of an indirect fluorescence immunoassay for the detection of serum
      antibodies against Babesia divergens in humans.
AB  - Since an indirect fluorescence immunoassay (IFA) for the detection of specific
      antibodies against Babesia divergens in human sera is not commercially available,
      an in-house prepared B. divergens IFA for the examination of bovine sera was
      established for serological studies in humans. To determine whether the described
      IFA is appropriate for such studies, 2 B. divergens antigens (of human or bovine
      origin) were tested using serum samples obtained from febrile human patients with
      a history of 'tick bite'. Sera from other species of animals infected with B.
      divergens, Babesia EU1, B. microti or B. canis were also included for comparative
      purposes. All serum samples were also tested using a commercially available IFA
      for the detection of antibodies against B. microti, and the results compared with
      those obtained using blood smear and molecular techniques. This study showed that
      the evaluation and standardization of a B. divergens IFA for testing human sera
      is critical and that different B. divergens antigens provide different end-point
      titres of antibodies, leading to false negative or positive results. Serological
      cross-reactivity between B. divergens and Babesia EU1 needs to be taken into
      account when interpreting IFA results.

PMID- 17032479
TI  - The NcGRA7 gene encodes the immunodominant 17 kDa antigen of Neospora caninum.
AB  - A Neospora caninum 17-19 kDa antigenic protein fraction (p17) in one-dimensional
      polyacrylamide gel electrophoresis (SDS-PAGE) is the immunodominant antigen
      recognized by sera from bovines naturally infected by N. caninum. To identify the
      proteins making up the p17 fraction, we screened a new N. caninum tachyzoite cDNA
      library with an affinity-purified antibody against p17 (APA17). We isolated
      several cDNA clones with 100% sequence identity to the NcGRA7 gene. This
      previously described gene encodes a dense granule protein with an apparent
      molecular mass of 33 kDa. A second line of evidence emerged through a combined
      proteomic approach associating two-dimensional PAGE (2D-PAGE) to Western blotting
      and to mass spectrometry to characterize the p17 fraction. Two acidic
      immunodominant but minority protein spots were recognized by APA17 and by bovine
      sera. These antigens of 17 and 33 kDa are respectively composed of 4 and 2
      isoforms. Furthermore, p17 isolation by 2D-PAGE and peptide sequencing by tandem
      mass spectrometry yielded a partial sequence of 17 amino acids, which allowed the
      putative amino terminal region of the NcGRA7 protein to be identified
      unambiguously. The NcGRA7 protein, without the putative signal peptide at the NH2
      terminus, was cloned and expressed in Escherichia coli and when the purified
      recombinant protein (rNcGRA7) was analysed by SDS-PAGE and mass spectrometry, 2
      bands of 24 and 33 kDa were resolved and identified as NcGRA7. These results
      demonstrate that the immunodominant 17 kDa antigen of N. caninum is encoded by
      the NcGRA7 gene.

PMID- 17032480
TI  - Simple epidemiological model predicts the relationships between prevalence and
      abundance in ixodid ticks.
AB  - We tested whether the prevalence of ticks can be predicted reliably from a simple
      epidemiological model that takes into account only mean abundance and its
      variance. We used data on the abundance and distribution of larvae and nymphs of
      2 ixodid ticks parasitic on small mammals (Apodemus agrarius, Apodemus
      flavicollis, Apodemus uralensis, Clethrionomys glareolus and Microtus arvalis) in
      central Europe. Ixodes trianguliceps is active all year round, occurs in the
      study area in the mountain and sub-mountain habitats only and inhabits mainly
      host burrows and nests, whereas Ixodes ricinus occurs mainly during the warmer
      seasons, occupies a large variety of habitats and quests for hosts outside their
      shelters. In I. ricinus, the models with k values calculated from Taylor's power
      law overestimated prevalences. However, if moment estimates of k corrected for
      host number were used instead, expected prevalences of both larvae and nymphs I.
      ricinus in either host did not differ significantly from observed prevalences. In
      contrast, prevalences of larvae and nymphs of I. trianguliceps predicted by
      models using parameters of Taylor's power law did not differ significantly from
      observed prevalences, whereas the models with moment estimates of k corrected for
      host number in some cases under-estimated relatively lower larval prevalences and
      over-estimated relatively higher larval prevalences, but predicted nymphal
      prevalences well.

PMID- 17032481
TI  - The interaction between the amoeba Balamuthia mandrillaris and extracellular
      matrix glycoproteins in vitro.
AB  - Balamuthia mandrillaris, a soil amoeba, is the causative agent of Balamuthia
      granulomatous amoebic encephalitis, a life-threatening brain infection. This
      amoeba is acquired from contaminated soil and may enter the host through
      cutaneous lesions or through nasal passages, migrating to the lungs or brain.
      During invasion, B. mandrillaris has access to components of the extracellular
      matrix (ECM) of the host. Therefore, we investigated the interaction of B.
      mandrillaris with 3 ECM glycoproteins (collagen-I, fibronectin and laminin-1)
      that are encountered in host connective tissues and at the basal lamina. Using
      optical microscopy, amoeba association on ECM-coated surfaces was examined.
      Binding of amoebae on laminin was greater than that on collagen or fibronectin.
      Laminin-adhered B. mandrillaris exhibited elongated and spread forms, distinctive
      from those observed for amoebae on a plastic surface. Collagen and fibronectin
      adhered B. mandrillaris presented elongated shapes with cellular expansions.
      Binding to collagen, fibronectin, or laminin was inhibited when amoebae were pre
      treated with sialic acid. Treatment with galactose resulted in diminished binding
      of amoebae on laminin, while mannose increased binding in all coating conditions
      tested. Dependence of divalent cations on amoeba binding was demonstrated for
      laminin-amoeba interaction. Collectively, the results indicate that B.
      mandrillaris recognizes specific glycoproteins of the mammalian extracellular
      matrix.

PMID- 17032482
TI  - Sustained peripheral arterial insufficiency durably impairs normal and
      regenerating skeletal muscle function.
AB  - Peripheral vascular occlusive diseases are frequently observed in humans, and
      studies with animal models have been largely used. However the effects of
      sustained lower limb ischemia on normal and regenerating hindlimb skeletal
      muscles are not well known in the mouse model. Therefore prolonged unilateral
      hindlimb ligation was generated by femoral artery ligation. Normal (myotoxic
      untreated) and regenerating (myotoxic-reated) ischemic muscles were studied by
      analyses of the in situ contractile properties and histological parameters.
      Concerning normal mouse muscles, we found that femoral artery ligation reduced
      hindlimb perfusion and altered muscle structure and function. Thus 7 days after
      ligation, maximal tetanic force was reduced by about 70%, (p < 0.05). By 56 days
      after ligation, muscle weights and cross-section areas of muscle fibers were
      still reduced (p < 0.05). Concerning myotoxic treated muscles, we report that
      ligation reduced the recovery of muscle weight and maximal tetanic force and
      increased fatigue resistance at 56 days (p < 0.05). In conclusion, our results
      demonstrate that sustained peripheral arterial insufficiency in mice induces long
      term as well as acute detrimental effects in both normal and regenerating
      muscles.

PMID- 17032483
TI  - Information, social support and anxiety before gastrointestinal endoscopy.
AB  - OBJECTIVES: To examine Lazarus and Folkman's (1984) stress theory regarding the
      effects of the stress mediators information and perceived social support on
      anxiety (as the stress response) regarding gastrointestinal (GI) endoscopy (as
      the stressor) in male and female patients of various age groups. DESIGN: Non
      experimental design. METHODS: Structured interviews were conducted with 113
      hospital out-patients about to undergo GI endoscopy. Participants indicated their
      perceptions of how much support and how much clear and useful information they
      had received from both their general practitioner (GP) and a patient information
      leaflet developed in collaboration with health psychologists as well as their
      perceptions of how much social support they had obtained from other patients,
      family and friends. Anxiety was measured with a population-specific trait and
      state adaptation of the Hospital anxiety and depression scale (HADS-A). RESULTS:
      Psychometric exploration of the HADS-A revealed a single general anxiety factor.
      The reliability of this factor was high, with Cronbach's alpha=0.91. The majority
      of the sample experienced high anxiety levels. Gender, but not age, differences
      emerged, showing females to be more anxious than males, F(1, 84)=5.68, p<.05. A
      regression model built on stress theory was tested, with anxiety as the dependent
      variable and 11 predictor variables. The model was significant with R(2)=0.452,
      F(11, 47)=3.522 and p=0.001. CONCLUSIONS: The clarity, but not the amount, of
      information and social support from important others, but not GPs, were both
      mediating the stress experience of the patients by reducing their perceived
      anxiety.

PMID- 17032484
TI  - Coping with ovarian cancer risk: the moderating effects of perceived control on
      coping and adjustment.
AB  - OBJECTIVE: Although perceived control and coping have been studied across various
      health conditions, these relationships have been less well studied in the context
      of coping with cancer risk over time. The present study was a longitudinal study
      of the effects of perceived control and problem-focused coping on changes in
      psychological adjustment and behavioural outcomes among women at increased risk
      for ovarian cancer. DESIGN AND METHODS: Eighty women enrolled in a familial
      cancer risk assessment programme participated in this study. Assessments of
      problem-focused coping, perceived control and distress were collected upon entry
      into the programme and again at 3-month follow-up. Behavioural adherence to
      screening during the 12-month period following programme entry was obtained from
      clinic records. RESULTS: Using hierarchical regression analysis, we observed a
      significant interaction between perceived control and problem-focused coping for
      psychological distress, beta=0.94, p<.05. Specifically, problem-focused coping
      was associated with increasing distress over time among women who perceived high
      control. A significant control by coping interaction was also observed for
      behavioural adherence to pelvic ultrasound and CA125 screening, such that women
      who perceived high control and utilized problem-focused coping were less likely
      to undergo screening. CONCLUSIONS: Under conditions of high perceived control,
      problem-focused coping was associated with increasing distress as well as poorer
      behavioural adherence. Thus, perceived control and problem-focused coping may not
      always yield positive psychological or behavioural health outcomes. These
      findings contribute to a greater understanding of how problem-focused coping and
      perceived control may influence the course of adjustment to cancer risk over
      time.

PMID- 17032485
TI  - Sample size for regression analyses of theory of planned behaviour studies: case
      of prescribing in general practice.
AB  - OBJECTIVES: Interest has been growing in the use of the theory of planned
      behaviour (TBP) in health services research. The sample sizes range from less
      than 50 to more than 750 in published TPB studies without sample size
      calculations. We estimate the sample size for a multi-stage random survey of
      prescribing intention and actual prescribing for asthma in British general
      practice. To our knowledge, this is the first systematic attempt to determine
      sample size for a TPB survey. METHODS: We use two different approaches: reported
      values of regression models' goodness-of-fit (the lambda method) and zero-order
      correlations (the variance inflation factor or VIF method). Intra-cluster
      correlation coefficient (ICC) is estimated and a socioeconomic variable is used
      for stratification. We perform sensitivity analysis to estimate the effects of
      our decisions on final sample size. RESULTS: The VIF method is more sensitive to
      the requirements of a TPB study. Given a correlation of .25 between intention and
      behaviour, and of .4 between intention and perceived behavioural control, the
      proposed sample size is 148. We estimate the ICC for asthma prescribing to be
      around 0.07. If 10 general practitioners were sampled per cluster, the sample
      size would be 242. CONCLUSIONS: It is feasible to perform sophisticated sample
      size calculations for a TPB study. The VIF is the appropriate method. Our
      approach can be used with adjustments in other settings and for other regression
      models.

PMID- 17032486
TI  - An electronic diary assessment of the effects of distraction and attentional
      focusing on pain intensity in chronic low back pain patients.
AB  - OBJECTIVE: The present study examined the effects of a manipulation of attention
      to pain (i.e. attentional focusing vs. distraction) on pain intensity in daily
      life of patients with chronic low back pain. It was hypothesized that attentional
      focusing would lead to decreased pain intensity in high pain fearful individuals,
      whereas distraction from pain would be associated with decreased pain intensity
      in low pain fearful individuals. DESIGN: An experience sampling methodology was
      used to examine the effects of a manipulation of attention to pain on pain
      intensity in daily life of pain patients. METHODS: A total number of 38 patients
      with chronic low back pain participated in this study and carried a palmtop
      computer for 2 weeks. During this period, patients were 'beeped' 8 times a day to
      complete diary questions. On certain days, instructions to either attend to or
      distract from pain were given. RESULTS: Multi-level analyses showed that
      attentional focusing was not associated with decreased pain intensity in high
      pain fearful individuals and that distraction did not lead to decreased pain
      intensity in low pain fearful individuals. The manipulations in isolation neither
      influenced pain intensity. The manipulation check was generally weak. CONCLUSION:
      A manipulation of attention to pain in daily life of patients with chronic low
      back pain proved difficult to accomplish. As the manipulation check was generally
      unsuccessful, no clear inferences about the underlying theory can be made. Future
      research within the field of pain treatments (e.g. in vivo exposure) might
      benefit greatly from electronic diary assessments studies.

PMID- 17032487
TI  - Predicting perceived vulnerability for breast cancer among women with an average
      breast cancer risk.
AB  - OBJECTIVES: The purpose of the present study was to investigate predictors of
      perceived vulnerability for breast cancer in women with an average risk for
      breast cancer. On the basis of empirical findings that suggested which variables
      might be associated with perceived vulnerability for breast cancer, we
      investigated whether knowledge of breast cancer risk factors, cancer worry,
      intrusions about breast cancer, optimism about not getting cancer and perceived
      health status have a predictive value for perceived breast cancer vulnerability.
      DESIGN: In a 3-step approach, we recruited 292 women from the general public in
      Germany who had neither a family history of breast cancer nor breast cancer
      themselves. After receiving an initial informational letter about study
      objectives, the women were interviewed by telephone and then asked to fill in a
      self-administered questionnaire. METHODS: We used structural equation modelling
      and hypothesized that each of the included variables has a direct influence on
      perceived vulnerability for breast cancer. RESULTS: We found a valid model with
      acceptable fit indices. Optimism about not getting cancer, intrusions about
      breast cancer and women's perceived health status explained 32% of the variance
      of perceived vulnerability for breast cancer. Cancer worry and knowledge about
      breast cancer did not influence perceived vulnerability for breast cancer.
      CONCLUSION: Perceived vulnerability for breast cancer is associated with health
      related variables more than with knowledge about breast cancer risk factors.

PMID- 17032488
TI  - Mind the gap... in intelligence: re-examining the relationship between inequality
      and health.
AB  - Wilkinson contends that economic inequality reduces the health and life
      expectancy of the whole population but his argument does not make sense within
      its own evolutionary framework. Recent evolutionary psychological theory suggests
      that the human brain, adapted to the ancestral environment, has difficulty
      comprehending and dealing with entities and situations that did not exist in the
      ancestral environment and that general intelligence evolved as a domain-specific
      adaptation to solve evolutionarily novel problems. Since most dangers to health
      in the contemporary society are evolutionarily novel, it follows that more
      intelligent individuals are better able to recognize and deal with such dangers
      and live longer. Consistent with the theory, the macro-level analyses show that
      income inequality and economic development have no effect on life expectancy at
      birth, infant mortality and age-specific mortality net of average intelligence
      quotient (IQ) in 126 countries. They also show that an average IQ has a very
      large and significant effect on population health but not in the evolutionarily
      familiar sub-Saharan Africa. At the micro level, the General Social Survey data
      show that, while both income and intelligence have independent positive effects
      on self-reported health, intelligence has a stronger effect than income. The data
      collectively suggest that individuals in wealthier and more egalitarian societies
      live longer and stay healthier, not because they are wealthier or more
      egalitarian but because they are more intelligent.

PMID- 17032489
TI  - Predicting self-efficacy using illness perception components: a patient survey.
AB  - OBJECTIVES: To assess the measures of illness representation components in
      predicting measures of self-efficacy in patients with coronary heart disease.
      DESIGN: A longitudinal design was adopted with predictor variables and dependent
      variables (general self-efficacy, diet self-efficacy and exercise self-efficacy)
      measured twice while participants were in hospital and 9 months following
      discharge. Change scores of the predictor variables can be calculated and
      dependent variables at baseline can be controlled. METHOD: A cohort sample of 300
      patients admitted to hospital with coronary heart disease were given the
      questionnaire measuring their illness perception (illness representation
      components: identity, consequences, timeline and control/cure and outcome
      expectation for diet and exercise); self-efficacy (general, diet and exercise
      self-efficacy measures), demographic and illness characteristics and attendance
      on a cardiac rehabilitation programme. The patients were asked to complete the
      questionnaire in hospital before discharge following their cardiac diagnosis, and
      again, 9 months later, when participants were expected to be functioning
      independently of any rehabilitation programme. RESULTS: Demographic and illness
      characteristics were found to have a more significant relationship with illness
      representation components than with specific self-efficacy. The relationship
      between illness representation components and specific self-efficacy changes
      overtime, consequence and timeline were significantly related to self-efficacy
      measures initially; however, symptom and control/cure were the variables that
      were significantly related to self-efficacy measures 9 months later. After
      statistically controlling individuals' baseline self-efficacy measures,
      demographic and illness characteristic effects, symptom and control/cure were
      found to make significant contributions to exercise and diet self-efficacy,
      respectively, 9 months later. CONCLUSION: A significant relationship exists
      between illness representation and self-efficacy. There is potential to integrate
      both approaches to the assessment of psychosocial factors to provide effective
      individualized care in cardiac rehabilitation.

PMID- 17032490
TI  - Future-directed thinking and depression in relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND: Research has shown that depression is associated with a view of the
      future characterized by reduced anticipation of future positive experiences, but
      not necessarily increased anticipation of future negative experiences. The aim of
      the present study was to investigate how participants with relapsing-remitting
      multiple sclerosis (MS) anticipated their future in terms of positive and
      negative events. DESIGN: A mixed design compared three groups of participants on
      a measure of future thinking using an adapted verbal fluency paradigm. METHODS:
      Depressed MS participants (N=14), non-depressed MS participants (N=28) and
      healthy control participants (N=26) were assessed on their ability to generate
      future positive and negative experiences. A content analysis was also conducted
      on the responses generated by the MS depressed and MS non-depressed groups
      according to whether or not they were related to MS. RESULTS: The MS depressed
      group anticipated significantly fewer future positive events than the healthy
      control group and the MS non-depressed group. The three groups did not differ in
      the total numbers of anticipated future negative events, though the MS depressed
      group did anticipate a significantly higher proportion of MS-related negative
      events. CONCLUSIONS: Like depressed but physically healthy individuals, the MS
      depressed group was characterized by a lack of positive thoughts about the
      future, rather than an increased number of negative thoughts. The clinical
      implications of these findings are discussed along with recommendations for
      future research.

PMID- 17032491
TI  - Targets and dimensions of social comparison among people with spinal cord injury
      and other health problems.
AB  - The present research examined comparison targets and comparison dimensions among
      two Spanish samples of individuals facing serious illnesses and diseases. In
      Study 1, 90 older patients (mean age 66.36) with various age-related diseases,
      particularly cardiovascular diseases and diabetes, indicated that they compared
      themselves most often with others with the same disease, next with others with
      another disease and least with people without health problems. They compared
      themselves more often on their mental state, symptoms and physical activities
      than on their social activities. Social comparison orientation (SCO) as an
      individual difference characteristic was associated with more frequent
      comparisons with particularly similar targets, and with more frequent comparisons
      of one's symptoms and physical activities. Neuroticism was correlated only with
      more comparisons of one's symptoms. Study 2 was conducted in a sample of 70
      relatively young patients (mean age 43.97) with spinal cord injury (SCI).
      Overall, they compared themselves more often with others than the participants in
      Study 1, and they compared themselves to a similar extent with people with SCI as
      with people with another disease and with people without health problems. While
      they felt on average better off than people with other diseases and other people
      with SCI, people with SCI felt on average worse off than people without health
      problems. They compared themselves more often on physical activities than on any
      other dimension. Higher levels of stress and uncertainty were associated with
      more frequent comparisons with people without SCI, and with more frequent
      comparisons of one's mental state, one's symptoms and one's future perspectives.
      The discussion focuses on the theoretical relevance of the results for social
      comparison theory, and on the practical relevance of the findings for
      interventions.

PMID- 17032492
TI  - Psychological distress after the occupation: A community cross-sectional survey
      from Lebanon.
AB  - OBJECTIVES: Jezzine inhabitants were exposed to war stressors for 17 years. This
      study aims at determining the prevalence of psychiatric distress (PD) among
      Jezzine citizens who were exposed to war for 17 years and to identify associated
      factors. DESIGN: Cross-sectional study. METHODS: A sample of 142 citizens was
      randomly selected from a population of 5,000. A novel questionnaire was used to
      collect data on war exposure, socioeconomic and demographic variables. PD was
      assessed using GHQ-12. Data were analysed by logistic regression. RESULTS: PD was
      found in 26% of Jezzine residents. PD was associated with age, marital status,
      education, experience of war-related events, chronic illness and alcohol
      drinking. After adjusting for all variables, PD remained significantly correlated
      with older age and low education (odds ratios were 7.59 and 4.28, respectively).
      CONCLUSIONS: The prevalence of PD among the residents of Jezzine after a year of
      the Israeli withdrawal was similar to that reported in other communities whether
      they were, or were not, exposed to war stress. Higher prevalence among older and
      less educated individuals suggests the presence of a significant age cohort
      effect and cognitive construal factors for PD among persons chronically exposed
      to war-related stressors.

PMID- 17032493
TI  - The meaning of self-perception of health in the UK armed forces.
AB  - OBJECTIVES: We assessed the characteristics of self-perception of health (SPH) in
      relation to psychological distress and physical symptoms, and willingness of
      servicemen to see their Medical Officer (MO) by their SPH rating. DESIGN: We
      randomly selected 4,500 servicemen to receive either a full or an abridged
      screening questionnaire. MEASURES: The full questionnaire included 6 items from
      the short-form 36 and the question on SPH, the General Health Questionnaire-12,
      the post-traumatic stress disorder checklist and 15 symptoms. The abridged
      questionnaire included a subset of items from the full questionnaire. All 'screen
      positive' and a random 'screen-negative' sample were invited to see an MO.
      RESULTS: 67.1% out of 4,500 servicemen completed the questionnaires. SPH was
      strongly associated with a summary short form-36 (SF-36) measure. There was a
      strong association between SPH and all assessment scales regardless of length of
      the questionnaires (p<.001). Even among those with very good or excellent SPH,
      high scores denoting psychological distress were prevalent (8.1%). Good SPH
      provided the largest variations in symptoms and scores. Servicemen with a
      poor/fair SPH were no more likely to accept a visit to the MO than the rest.
      CONCLUSIONS: SPH is an excellent question for surveillance because it is highly
      associated with psychological health but, at an individual level, it may convey
      different meanings depending on the person's individual interpretation of the
      term health. Symptomatic social avoidance may be high among servicemen who have a
      poor/fair SPH and methods, such as buddy support, may be helpful in decreasing
      isolation among those who may need professional support.

PMID- 17032494
TI  - Longitudinal gains in self-regulation from regular physical exercise.
AB  - OBJECTIVES: The purpose of the present study was to test whether the repeated
      practice of self-regulation could improve regulatory strength over time. METHOD:
      Regulatory performance was assessed at baseline, then at monthly intervals for a
      period of 4 months using a visual tracking task. Perceived stress, emotional
      distress, self-efficacy and general regulatory behaviour were assessed by
      questionnaire. Following a 2-month control phase, participants entered a 2-month
      self-regulation programme designed to increase regulatory strength: a programme
      of regular physical exercise. RESULTS: Relative to the control phase,
      participants who exercised showed significant improvement in self-regulatory
      capacity as measured by an enhanced performance on the visual tracking task
      following a thought-suppression task. During the regulatory exercise phase,
      participants also reported significant decreases in perceived stress, emotional
      distress, smoking, alcohol and caffeine consumption, and an increase in healthy
      eating, emotional control, maintenance of household chores, attendance to
      commitments, monitoring of spending and an improvement in study habits. The
      control phase showed no systematic changes in performance on the visual tracking
      task across sessions. Reports of perceived stress, emotional distress and
      regulatory behaviours were also stable across sessions. CONCLUSIONS: The uptake
      and maintenance of an exercise programme over a 2-month period produced
      significant improvements in a wide range of regulatory behaviours. Nearly every
      major personal and social problem has some degree of regulatory failure. The idea
      that the capacity for self-regulation can be improved is therefore of vast
      practical importance.

PMID- 17032495
TI  - Effect of intratumoral injection on the biodistribution and the therapeutic
      potential of HPMA copolymer-based drug delivery systems.
AB  - The direct intratumoral (i.t.) injection of anticancer agents has been evaluated
      extensively in the past few decades. Thus far, however, it has failed to become
      established as an alternative route of administration in routine clinical
      practice. In the present report, the impact of i.t. injection on the
      biodistribution and the therapeutic potential of N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer-based drug delivery systems was
      investigated. It was found that, compared to intravenous injection, both the
      tumor concentrations and the tumor-to-organ ratios of carriers improved
      substantially. In addition, compared to intravenously and intratumorally applied
      free doxorubicin and to intravenously applied poly(HPMA)
      glycylphenylalanylleucylglycine-doxorubicin, intratumorally injected poly(HPMA)
      glycylphenylalanylleucylglycine-doxorubicin presented a significantly increased
      antitumor efficacy, as well as an improved therapeutic index. Based on these
      findings, we propose intratumorally injected carrier-based chemotherapy as an
      interesting alternative to routinely used chemotherapy regimens and routes of
      administration.

PMID- 17032496
TI  - Noninvasive optical tracking of red fluorescent protein-expressing cancer cells
      in a model of metastatic breast cancer.
AB  - We have evaluated the use of the Xenogen IVIS 200 imaging system for real-time
      fluorescence protein-based optical imaging of metastatic progression in live
      animals. We found that green fluorescent protein-expressing cells (100 x 10(6))
      were not detectable in a mouse cadaver phantom experiment. However, a 10-fold
      lower number of tdTomato-expressing cells were easily detected. Mammary fat pad
      xenografts of stable MDA-MB-231-tdTomato cells were generated for the imaging of
      metastatic progression. At 2 weeks postinjection, barely palpable tumor burdens
      were easily detected at the sites of injection. At 8 weeks, a small contralateral
      mammary fat pad metastasis was imaged and, by 13 weeks, metastases to lymph nodes
      were detectable. Metastases with nodular composition were detectable within the
      rib cage region at 15 weeks. 3-D image reconstructions indicated that the
      detection of fluorescence extended to approximately 1 cm below the surface. A
      combination of intense tdTomato fluorescence, imaging at > or = 620 nm (where
      autofluorescence is minimized), and the sensitivity of the Xenogen imager made
      this possible. This study demonstrates the utility of the noninvasive optical
      tracking of cancer cells during metastatic progression with endogenously
      expressed fluorescence protein reporters using detection wavelengths of > or =
      620 nm.

PMID- 17032497
TI  - Human cytomegalovirus infection alters PC3 prostate carcinoma cell adhesion to
      endothelial cells and extracellular matrix.
AB  - The genome and antigens of human cytomegalovirus (HCMV) are frequently found in
      prostatic carcinoma. However, whether this infection is causative or is an
      epiphenomenon is not clear. We therefore investigated the ability of HCMV to
      promote metastatic processes, defined by tumor cell adhesion to the endothelium
      and extracellular matrix proteins. Experiments were based on the human prostate
      tumor cell line PC3, either infected with the HCMV strain Hi (HCMV(Hi)) or
      transfected with cDNA encoding the HCMV-specific immediate early protein IEA1
      (UL123) or IEA2 (UL122). HCMV(Hi) upregulated PC3 adhesion to the endothelium and
      to the extracellular matrix proteins collagen, laminin, and fibronectin. The
      process was accompanied by enhancement of beta(1)-integrin surface expression,
      elevated levels of integrin-linked kinase, and phosphorylation of focal adhesion
      kinase. IEA1 or IEA2 did not modulate PC3 adhesion or beta(1)-integrin
      expression. Based on this in vitro model, we postulate a direct association
      between HCMV infection and prostate tumor transmigration, which is not dependent
      on IEA proteins. Integrin overexpression, combined with the modulation of
      integrin-dependent signalling, seems to be, at least in part, responsible for a
      more invasive PC3(Hi) tumor cell phenotype. Elevated levels of c-myc found in
      IEA1-transfected or IEA2-transfected PC3 cell populations might promote further
      carcinogenic processes through accelerated cell proliferation.

PMID- 17032498
TI  - Overexpression of PIAS3 suppresses cell growth and restores the drug sensitivity
      of human lung cancer cells in association with PI3-K/Akt inactivation.
AB  - Constitutively activated signal transducers and activators of transcription
      (STAT) are reported to cause uncontrolled transmission of growth signals. In this
      study, we analyzed the roles of an inhibitor of STAT, protein inhibitor of
      activated STAT (PIAS) 3, in the development of lung cancer. Treatment with an
      inhibitor of phosphatidylinositol 3-kinase, LY294002, retarded the growth of
      human lung cancer cells and rendered them more sensitive to chemotherapeutic
      agents. However, the inhibition of JAK/STAT by AG490 significantly suppressed
      cell growth but did not increase drug sensitivity at all. Overexpression of PIAS3
      not only significantly inhibited cell growth but also rendered cancer cells up to
      12.0-fold more sensitive to the above drugs, which was associated with the
      suppression of Akt phosphorylation. Inhibition of PIAS3 with small interfering
      RNA, nevertheless, led cancer cells to accelerate cell proliferation, deteriorate
      chemosensitivity, and augment Akt phosphorylation. Although the overexpression of
      suppressors of cytokine signaling 3 in cancer cells also inhibited cell growth
      and STAT3 phosphorylation, it neither increased sensitivity to chemotherapeutic
      drugs nor affected the phosphorylation of Akt. These results indicate that PIAS3
      may be an attractive candidate for targeting the JAK/STAT and PI3-K/Akt signaling
      pathways in cancer treatment.

PMID- 17032499
TI  - TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy
      number changes in prostate carcinomas and paired HGPIN lesions.
AB  - TMPRSS2-ETS gene fusions have been found recurrently in prostate carcinomas, but
      not in the presumed precursor lesion, high-grade prostatic intraepithelial
      neoplasia (HGPIN). However, HGPIN lesions may share chromosomal changes with
      prostate cancer. To determine the relative order of genetic events in prostate
      carcinogenesis, we have analyzed 34 prostate carcinomas, 19 paired HGPIN lesions,
      14 benign prostate hyperplasias, and 11 morphologically normal prostatic tissues
      for TMPRSS2-ERG and TMPRSS2-ETV1 rearrangements and genomic imbalances. TMPRSS2
      exon 1 was fused in-frame with ERG exon 4 in 17 of 34 (50%) prostate carcinomas
      and in 4 of 19 (21%) HGPIN lesions, but in none of controls. The findings were
      further validated by sequencing analysis and by the real-time polymerase chain
      reaction quantification of TMPRSS2-ERG fusion transcript and the ERG exons
      5/6:exons 1/2 expression ratio. Chromosome copy number changes were detected by
      comparative genomic hybridization in 42% of clinically confined carcinomas and in
      none of the 16 HGPIN lesions analyzed. We demonstrate for the first time that the
      TMPRSS2-ERG fusion gene can be detected in a proportion of HGPIN lesions and that
      this molecular rearrangement is an early event that may precede chromosome-level
      alterations in prostate carcinogenesis.

PMID- 17032500
TI  - Tumor mRNA-transfected dendritic cells stimulate the generation of CTL that
      recognize neuroblastoma-associated antigens and kill tumor cells:
      immunotherapeutic implications.
AB  - Several observations suggest a potential role of T-cell-mediated immunity in the
      control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T
      lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells
      (DC) has never been investigated before. In the present study, the feasibility of
      this strategy has been analyzed, both in healthy donors and in NB patients.
      Monocyte-derived DC were raised from three human leukocyte antigen (HLA) A2+ NB
      patients and seven HLA-A1+ or HLA-A2+ healthy donors transfected with mRNA from
      four NB cell lines and cocultured with autologous CD8+ lymphocytes. Expanded CTL
      expressed an effector/memory phenotype and a T cytotoxic 1-like profile of
      cytokine secretion. CTL specificity was demonstrated by interferon-gamma release
      on incubation with HLA-matched NB cell lines. The latter cell lines, but not
      autologous T-cell blasts, were lysed by CTL in an HLA-restricted manner.
      Cytotoxicity was found to involve the release of granzyme B. When tested for
      reactivity against NB-associated antigens, CTL from normal individuals recognized
      anaplastic lymphoma-associated kinase (ALK) and preferentially expressed antigen
      of melanoma (PRAME) peptides only, whereas patients' CTL reacted also to
      survivin, telomerase, and tyrosine hydroxylase peptides. This study demonstrates
      that DC transfected with NB mRNA induce the generation of patients' CTL specific
      for different NB-associated antigens, supporting the feasibility of NB T-cell
      immunotherapy.

PMID- 17032501
TI  - Expression of calcium-binding proteins S100A2 and S100A4 in Barrett's
      adenocarcinomas.
AB  - In this study, we investigated the mRNA and protein expression of S100A2 and
      S100A4 in adenocarcinomas of the stomach and esophagus. Real-time reverse
      transcription-polymerase reaction analysis on 72 tumors revealed frequent
      overexpression of S100A2 and S100A4 in Barrett's adenocarcinomas (BAs) (P < .01).
      Immunohistochemical analysis on tumor tissue microarrays that contained 187
      tumors showed absent to weak staining for S100A2 in all normal gastric mucosa
      samples, whereas normal esophageal mucosa samples demonstrated moderate to strong
      nuclear staining. Contrary to the nuclear expression of S100A2 in normal
      esophageal mucosa, two thirds of Barrett's dysplasia and BAs that overexpressed
      S100A2 demonstrated stronger cytosolic staining than nuclear staining (P < .001).
      Overexpression of S100A2 protein was more frequently seen in well-differentiated
      tumors than in others (P = .02). Moderate to strong staining of S100A4 was
      detected in two thirds of tumors and was frequently observed in the presence of
      Barrett's esophagus (P = .02). Similar to S100A2, the expression of S100A4 was
      predominantly cytosolic in two thirds of the tumors (P = .001). There was a
      significant correlation between S100A4 overexpression and lymph node metastasis
      (N(2)-N(4)) (P = .027). These results demonstrate frequent cytosolic
      overexpression of S100A2 and S100A4 in BAs. Further studies are ongoing to
      understand the biological significance of these S100A proteins in Barrett's
      tumorigenesis.

PMID- 17032502
TI  - Cellular and molecular consequences of peroxisome proliferator-activated receptor
      gamma activation in ovarian cancer cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand
      activated transcription factor. In addition to its canonical role in lipid and
      glucose metabolism, PPAR-gamma controls cell proliferation, death, and
      differentiation in several tissues. Here we have examined the expression of PPAR
      gamma in ovarian tumors and the cellular and molecular consequences of its
      activation in ovarian cancer cells. PPAR-gamma was expressed in a large number of
      epithelial ovarian tumors and cell lines. The PPAR-gamma ligand ciglitazone
      inhibited the growth and clonogenic survival of ovarian cancer cells, inducing
      cell cycle arrest and cell death. Growth inhibition by ciglitazone was reversed
      by the PPAR-gamma antagonist GW9662, indicating the involvement of PPAR-gamma
      dependent mechanisms. Microarray-based gene profiling revealed complex changes in
      the transcriptional program of ovarian cancer cells on treatment with ciglitazone
      and identified multiple pathways that may contribute to PPAR-gamma ligands'
      antitumor activity. Genes upregulated by ciglitazone were predominantly
      associated with metabolic, differentiation, and tumor-suppressor pathways,
      whereas downregulated genes were involved in cell proliferation, cell cycle, cell
      organization, and steroid biosynthesis. Collectively, our data indicate that PPAR
      gamma activation by selective agonists is a valid strategy for ovarian cancer
      therapy and prevention, and should be tested alone and in combination with other
      anticancer drugs.

PMID- 17032504
TI  - Heparanase expression in malignant salivary gland tumors inversely correlates
      with long-term survival.
AB  - BACKGROUND: Upregulation of the endo-beta-D-glucuronidase, heparanase, was noted
      in an increasing number of human malignancies. Heparanase expression correlated
      with enhanced local and distant metastatic spread, increased vascular density,
      and reduced postoperative survival. PATIENTS AND METHODS: We analyzed heparanase
      expression in 60 patients (aged 59 +/- 17 years) with malignant salivary tumors
      (39 males and 21 females) using immunohistochemistry. We applied antiheparanase
      antibody 733, which has previously been shown to preferentially recognize a 50
      kDa active heparanase subunit over a 65-kDa latent enzyme. Thus, immunostaining
      can directly be correlated with enzymatic activity. RESULTS: Heparanase staining
      was positive (> 0) in 70% of tumors (42 of 60 patients) and was negative (0) in
      the remaining 30% (18 patients). The cumulative survival of patients diagnosed as
      heparanase-negative (n = 18) at 300 months was 70% (95% confidence interval = 35
      88). In contrast, the cumulative survival of patients diagnosed as heparanase
      positive (n = 42) at 300 months was 0% (statistically significant difference, P =
      .035). CONCLUSIONS: Heparanase expression levels inversely correlate with the
      survival rates of salivary gland cancer patients, clearly indicating that
      heparanase is a reliable prognostic factor for this malignancy and an attractive
      target for anticancer drug development.

PMID- 17032503
TI  - Inhibition of androgen-independent prostate cancer by estrogenic compounds is
      associated with increased expression of immune-related genes.
AB  - The clinical utility of estrogens for treating prostate cancer (CaP) was
      established in the 1940s by Huggins. The classic model of the anti-CaP activity
      of estrogens postulates an indirect mechanism involving the suppression of
      androgen production. However, clinical and preclinical studies have shown that
      estrogens exert growth-inhibitory effects on CaP under low-androgen conditions,
      suggesting additional modes whereby estrogens affect CaP cells and/or the
      microenvironment. Here we have investigated the activity of 17beta estradiol (E2)
      against androgen-independent CaP and identified molecular alterations in tumors
      exposed to E2. E2 treatment inhibited the growth of all four androgen-independent
      CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, and LuCaP 58) in
      castrated male mice. The molecular basis of growth suppression was studied by
      cDNA microarray analysis, which indicated that multiple pathways are altered by
      E2 treatment. Of particular interest are changes in transcripts encoding proteins
      that mediate immune responses and regulate androgen receptor signaling. In
      conclusion, our data show that estrogens have powerful inhibitory effects on CaP
      in vivo in androgen-depleted environments and suggest novel mechanisms of
      estrogen-mediated antitumor activity. These results indicate that incorporating
      estrogens into CaP treatment protocols could enhance therapeutic efficacy even in
      cases of advanced disease.

PMID- 17032505
TI  - Contraception in crisis.

PMID- 17032506
TI  - Tackling the unacceptable: Nigeria approves misoprostol for postpartum
      haemorrhage.

PMID- 17032507
TI  - Abortion law: campaign groups and the quest for change.

PMID- 17032508
TI  - Accessibility of condoms to young people in Manchester, UK.
AB  - BACKGROUND AND METHODOLOGY: Issues relevant to the accessibility of male condoms
      for young people in the Greater Manchester area (UK) were investigated, using
      semi-structured, in-depth interviews and a questionnaire survey. RESULTS: Family
      planning clinics and condom vending machines (CVMs) were the most cited sources
      for condom acquisition. Young people's knowledge of where and when they could
      access condoms varied by age and gender. Suitable positioning of CVMs would need
      to take such variations into account when targeting potential customers. Levels
      of embarrassment about acquiring condoms also varied according to gender. The
      lifestyles of young people indicated the sorts of places in which CVMs might
      offer increased accessibility. For younger men and women this tended to involve
      low-cost, semi-private places such as local parks, school toilets and shopping
      malls/streets. Older men with higher spending power and increased confidence
      could access condoms through pub and club toilets and chemist shops. CONCLUSIONS:
      Accessible positioning of CVMs was related to the age, gender and lifestyle of
      the participants, and programmes to enhance accessibility should reflect this.
      Increased accessibility for younger groups, and especially women, needs to take
      into account issues of cost, confidence and embarrassment. For older groups,
      lifestyle choices indicated pubs and clubs as key locations for both men and
      women.

PMID- 17032509
TI  - The importance of contextualisation in giving a diagnosis of genital chlamydial
      infection: findings from a qualitative study.
AB  - OBJECTIVE: To explore the impact of diagnostic communication upon the way in
      which people receive and respond to a diagnosis of chlamydial infection. METHODS:
      A qualitative study examining the responses of individuals to a diagnosis of
      chlamydial infection. The study was conducted in a genitourinary medicine clinic
      and a family planning clinic in the Midlands region of the UK. The sample size
      was 50 and included both males and females. Data collection was by means of
      unstructured interviews, which were audio-taped and fully transcribed. The
      principles of grounded theory were followed in the sampling, analysis and
      exploration of the literature. RESULTS: A diagnosis of chlamydial infection was
      commonly unexpected and associated with negative reactions, which derived from
      the social construction of sexually transmitted infections as evidence of
      breaching the moral code. The way in which the health professional communicated
      the diagnosis contributed to the patient response, either negatively by
      reinforcing feelings of self-recrimination or positively by the provision of key
      information that appeared to be helpful in modifying that response. CONCLUSION:
      Sensitive management and the provision of contextualised information serve an
      important function for those diagnosed with chlamydial infection.

PMID- 17032511
TI  - Low literacy: a hidden problem in family planning clinics.
AB  - OBJECTIVES: Low literacy is highly prevalent among UK adults. This study assessed
      functional health literacy among family planning clinic clients and whether this
      was associated with sexual health knowledge and behaviours. It also assessed the
      readability of patient leaflets. METHODS: 505 female family planning clinic
      attendees aged 16-35 years were interviewed about their sexual behaviour and
      knowledge. Their reading age was assessed using a validated test (REALM). The
      readability of leaflets on contraception supplied to clinic users was measured.
      RESULTS: All respondents had a reading age of 12 years and above, 221 (43.8%)
      between 12 and 14 years and 284 (56.2%) greater than 14 years. Those in the lower
      literacy group were significantly more likely to have been aged under 16 years at
      time of first sexual intercourse, and significantly less likely to know the most
      fertile time of the menstrual cycle, to identify sexually transmitted infections
      and to know that sexual infections can be transmitted through oral and anal sex.
      The reading age of information leaflets in the clinics ranged from 11 to 17
      years. Thus, clients with a reading level of 12-14 years would have difficulty in
      understanding some of the leaflets. CONCLUSIONS: Functional health literacy is
      related to sexual behaviour and knowledge. Written information should be prepared
      with this in mind and other routes of communication considered.

PMID- 17032512
TI  - Consumer behaviour and contraceptive decisions: resolving a decades-long puzzle.

PMID- 17032510
TI  - Quality of delivery of the Standard Days Method as compared with contraceptive
      pills in Rwanda.
AB  - BACKGROUND AND METHODOLOGY: Replicating a Peruvian study, this research
      introduced the Standard Days Method (SDM) into Rwanda Ministry of Health clinics
      and evaluated client counselling on the new method against that given for
      contraceptive pills. Providers received technical reinforcement concerning
      established methods in addition to SDM training. To evaluate their quality of
      care, simulated clients implemented a service test in visits to 20 clinics.
      RESULTS: As in Peru, providers exchanged significantly more relevant information
      with clients who chose SDM than with those who chose pills. Also, a minority of
      providers posed barriers to SDM access by refusing to give SDM tools to the
      client until she brought her partner for consultation. CONCLUSIONS: The findings
      of this study confirm that SDM counselling is generally satisfactory, although
      SDM training needs adjustment, and that the rigour of providers' pill counselling
      remains below capacity.

PMID- 17032517
TI  - Reproductive health in domestic animals.

PMID- 17032518
TI  - Delphi method and nominal group technique in family planning and reproductive
      health research.

PMID- 17032519
TI  - Primary ovarian pregnancy with a levonorgestrel intrauterine system.

PMID- 17032520
TI  - Implanon and alopecia.

PMID- 17032521
TI  - Premenstrual syndrome: a plea for greater understanding.

PMID- 17032522
TI  - Are your patients' emotions blocking their understanding?

PMID- 17032523
TI  - Obtaining valid consent.

PMID- 17032524
TI  - "Clean-up consultant to aisle 69 please".

PMID- 17032525
TI  - In condoms we trust: to each, one's own.

PMID- 17032527
TI  - The French pox.

PMID- 17032528
TI  - Liquid-based cytology.

PMID- 17032529
TI  - Increase in IUD expulsions.

PMID- 17032530
TI  - Oral contraceptives and diabetes mellitus: an update.

PMID- 17032532
TI  - Full-term pregnancy with Implanon in situ.

PMID- 17032533
TI  - Full-term pregnancy with Implanon in situ.

PMID- 17032534
TI  - Full-term pregnancy with Implanon in situ.

PMID- 17032535
TI  - Implanon insertion.

PMID- 17032538
TI  - Pelvic actinomycosis.

PMID- 17032541
TI  - Genetic influences on free and cued recall in long-term memory tasks.
AB  - Long-term memory (LTM) problems are associated with many psychiatric and
      neurological illnesses and are commonly measured using free and cued recall
      tasks. Although LTM has been linked with biologic mechanisms, the etiology of
      distinct LTM tasks is unknown. We studied LTM in 95 healthy female twin pairs
      identified through birth records in the state of Missouri. Performance on tasks
      of free recall of unrelated words, free and cued recall of categorized words, and
      the vocabulary section of the Wechsler Adult Intelligence Scale (WAIS-R) were
      examined using structural equation modeling. Additive genetic and unique
      environmental factors influenced LTM and intelligence. Free recall of unrelated
      and categorized words, and cued recall of categorized words, were moderately
      heritable (55%, 38%, and 37%). WAIS-R vocabulary score was highly heritable
      (77%). Controlling for verbal intelligence in multivariate analyses of recall,
      two components of genetic influence on LTM were found; one for all three recall
      scores and one for free and cued categorized word recall. Recall of unrelated and
      categorized words is influenced by different genetic and environmental factors
      indicating heterogeneity in LTM. Verbal intelligence is etiologically different
      from LTM indicating that these two abilities utilize different brain functions.

PMID- 17032542
TI  - Sex differences in symptoms of depression in unrelated individuals and opposite
      sex twin and sibling pairs.
AB  - Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual
      of Mental Disorders of the American Psychiatric Association requires 5 out of 9
      symptoms to be present. Therefore, individuals may differ in the specific
      symptoms they experience and reach a diagnosis of depression via different
      pathways. It has been suggested that depressed women more often report symptoms
      of sleep disturbance, appetite or weight disturbance, fatigue, feelings of
      guilt/worthlessness and psychomotor retardation than depressed men. In the
      current study, we investigate whether depressed men and women differ in the
      symptoms they report. Two samples were selected from a sample of Dutch and
      Australian twins and siblings. First, Dutch and Australian unrelated depressed
      individuals were selected. Second, a matched epidemiological sample was created
      consisting of opposite-sex twin and sibling pairs in which both members were
      depressed. No sex differences in prevalence rates for symptoms were found, with
      the exception of decreased weight in women in the sample of unrelated
      individuals. In general, the similarities in symptoms seem to far out-weigh the
      differences in symptoms between men and women. This signifies that men and women
      are alike in their symptom profiles for major depression and genes for depression
      are probably expressed in the same way in the two sexes.

PMID- 17032543
TI  - Nonadditive genetic effects on hostility in South Korean adolescent and young
      adult twins.
AB  - Hostility has been shown to be a vulnerability marker for various health
      problems. The present study examined genetic and environmental contributions to
      individual differences in hostility in South Korean adolescent and young adult
      twins. Seven hundred and nineteen same- and opposite-sex twin pairs aged from 13
      to 23 years completed a hostility scale. The scalar sex-limitation model was
      applied to the data. The best fitting model indicated that 34% of the total
      variation of hostility was attributable to genetic factors operating in a
      nonadditive manner. The remaining 66% of the variance was associated with
      nonshared environmental influences and measurement error. These findings were
      largely consistent with results from previous twin studies of personality based
      on Caucasian twins, rendering support for the pervasive influence of genetic
      nonadditivity on human personality traits and the generalization of the
      heritability of personality across human populations.

PMID- 17032544
TI  - Suicidal behavior in surviving co-twins.
AB  - Recent research has provided strong support for the existence of a familial risk
      for suicide, and efforts have been made to separate genetic from enviromental
      risk factors. Twin studies have played a major role in the identification of
      genetic factors, and the results indicate that the concordance rate for suicide
      is higher in identical than in fraternal twins (Baldessarini & Hennen, 2004).
      Moreover, Segal and Roy (1995) reported a significantly higher frequency of
      nonfatal suicidal attempts by monozygotic (MZ) than by dyzygotic (DZ) twins whose
      co-twins had committed suicide. However, doubts remain as to whether the
      increased risk of suicide in MZ twins is a response to the intense grief over the
      loss of a close relative, or whether a common genotype is associated with
      suicidal behavior. Sudden loss, which may carry a stigma in the case of a
      suicide, has been linked to increased persistent emotional stress and
      physiological changes (Epstein, 1993; Martin & Dean, 1993). A number of
      researchers have reported greater suicidal ideation among bereaved MZ twins as
      compared to DZ twins, suggesting that a loss due to suicide may increase the risk
      of suicidal behavior in the surviving co-twin (Segal & Bouchard, 1993; Segal &
      Roy, 1995; Segal et al., 1995). The aim of the present article is to address the
      issue of the intense grief experienced by twins after the co-twin suicide.

PMID- 17032545
TI  - Body size in five-year-old twins: heritability and comparison to singleton
      standards.
AB  - The aim of this study is to examine causes of individual differences in height,
      weight and body mass index (BMI) in 5-year-old children registered with the
      Netherlands Twin Register. In addition, we examine whether the results of twin
      studies can be expanded to the singleton population by comparing the data from
      twins to Dutch reference growth data and by looking at the twins' target height,
      which was derived from parental height. For 2996 5-year-old twin pairs,
      information on height and weight and on parental height was available. Univariate
      and bivariate genetic analyses of height and weight and univariate analyses of
      BMI were conducted. In order to compare the twins to the singleton population,
      standard deviation scores (SDS) for height, BMI and target height were calculated
      based on Dutch reference growth charts for the general population from 1997.
      Genetic influences were an important source of variation in height, weight and
      BMI and the main source of covariation between height and weight. Additive
      genetic factors accounted for 69% and 66% of the individual differences in height
      in boys and girls, respectively. For weight, heritability estimates were 59% in
      boys and 78% in girls and for BMI 34% and 74%. The influence of common
      environment on height was 25% and 27%, on weight 24% and 10% and on BMI 44% and
      12% in boys and girls. The bivariate model showed a large overlap between the
      genes influencing height and weight. Genes explain 78% (in boys) and 76% (in
      girls) of the covariance between weight and height. At the age of 5 years, female
      twins were as tall as singleton children, while male twins were shorter than
      singletons. For both boys and girls, however, mean height SDS was 0.6 standard
      deviation scores below the mean target height. All twins had lower BMI than
      singletons. Twins grow fairly well compared to singletons, but they grow below
      their target height. This may be due to the above average height of twin parents.

PMID- 17032546
TI  - Maternal dietary intake in twin pregnancies: does it diminish towards term?
AB  - We tested the hypothesis that energy intake among women with twin pregnancies
      decreases in late gestation, as the uterus enlarges and they become increasingly
      uncomfortable. We asked women to recall dietary intake for the previous 24 hours,
      every 2 weeks from around 29 weeks of gestation, using a photographic atlas and
      other strategies to estimate portion size. Eighty women provided data at around
      29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and
      energy intake from carbohydrate, fat and protein. Data were log transformed to
      reduce skewness. Using mixed effects linear regression models, we found minimal
      evidence that total energy intake changed over this time period, either before or
      after adjustment for potential confounding factors (95% confidence interval for
      relative change per week: -1.4%, 0.6%). There was weak evidence of a small
      decline in carbohydrate intake over time, both before and after controlling for
      energy intake. We cannot exclude change in energy intake or diet composition
      before 29 weeks or after 35 weeks of twin gestation.

PMID- 17032547
TI  - Birthweight discordance in twins and the risk of being heavier for respiratory
      distress syndrome.
AB  - Twin pregnancies are becoming common as a result of increased assisted
      reproduction. Studies have shown that the smaller twin of a pair is at greater
      risk of morbidity and mortality. Our aim was to determine if there is a relation
      between birth-weight discordancy and neonatal morbidity and mortality and to test
      the occurrence of respiratory distress syndrome (RDS) in discordant twins. For 5
      years all twins admitted to our intensive care unit were included in the study.
      Discordance was calculated as the difference between twins' weights divided by
      the heavier weight. Diagnosis of RDS was made by typical clinical and
      radiographic methods. Multiple logistic regression was performed with gender,
      weight order and birth order as the independent variables and RDS as the
      dependent variable. Two hundred and sixty-six twin pairs with a mean gestation of
      33 weeks and a mean birth-weight of 1890 g were evaluated. Multiple logistic
      regression revealed that being the heavier twin was a more important risk factor
      for RDS (odds ratio 4.5; 95% confidence interval 2.2-9.2) than being the male or
      second-born twin. Based on neonatal outcomes a birth-weight discordance equal or
      greater than 20% in twin pairs was accepted as the discordance criterion.
      Discordant and concordant groups were statistically different in neonatal
      mortality, necrotizing enterocolitis, polycytemia and hypoglycemia. Our data
      demonstrated that being the heavier twin is a risk factor for RDS and a birth
      weight difference of 20% or more in twin pairs should be accepted as discordance.

PMID- 17032548
TI  - Curves of placental weights of live-born twins.
AB  - The purpose of this study is to present curves of estimated placental growth in
      twins and to evaluate the relative contribution of gestational age, zygosity,
      chorionicity, fusion of the placentas, sex of the individual and of the twin
      pair, site of the umbilical cord insertion, birth order, maternal age, and
      parity. Perinatal data and placental data were obtained from 6315 live-born twin
      pairs from the East Flanders Prospective Twin Survey. Of 4318 twin pairs, with no
      missing values, the placental weights of different gestational ages were analyzed
      using a nonlinear multivariate Gaussian regression. Two groups were
      distinguished: (1) twins with two separate placentas, and (2) twins with only one
      placental mass (one placenta in case of monochorionic twins or two fused
      placentas in case of dichorionic placentas). Overall, placental weight was
      influenced by gestational age, fusion of the placentas, and parity. In the case
      of one placental mass, monozygotic dichorionic twins had the lowest weights. If
      two separate placentas were present, birth order played a role in favor of the
      first-born twin. For parity and zygosity, the differences were most pronounced
      between 27 and 29 weeks, whereas the difference for birth order was most
      pronounced between 33 and 37 weeks. In conclusion, basic physiological
      characteristics, routinely examined at birth, influence placental weight. Taking
      these covariates into account allows a better evaluation of the placental weight
      given a gestational age, as an indicator of growth.

PMID- 17032549
TI  - Twinning and risk of stillbirth subtypes in pediatric mothers.
AB  - We sought to estimate levels of risk for stillbirth subtypes associated with twin
      gestations among pediatric mothers (10-14 years). Analysis was on twin
      pregnancies covering the period 1989 to 2000 in the United States. We classified
      stillbirth as term, preterm, small-for-gestational-age (SGA) or preterm-SGA. We
      then assessed the risks of these stillbirth subtypes in pediatric mothers using
      two comparison groups consisting of women aged 15 to 19 years old (adolescent
      mothers) and 20 to 24 years old (mature mothers). Adjusted risk estimates were by
      means of hazard ratios generated from a Cox proportional hazards regression
      model. We adjusted for dependence of observations within twin clusters using the
      robust sandwich estimator. The rate of stillbirth was highest among pediatric
      mothers (56/1000), followed by adolescent gravidas (29/1000) and lowest in mature
      mothers (20/1000; p for trend < .01). Overall, preterm stillbirth was the most
      frequent stillbirth phenotype while term stillbirth was the least frequent. Not a
      single case of term stillbirth was recorded in pediatric mothers. Among pediatric
      gravidas, the risk for preterm stillbirth was more than tripled (adjusted hazard
      ratio [AHR] = 3.4; 95% confidence interval [CI] = 2.5-4.6), and that of preterm
      SGA stillbirth more than doubled (AHR = 2.6; 95% CI = 1.8-3.7) that of mature
      mothers respectively. The 30% risk elevation for SGA stillbirth among pediatric
      mothers was not found to be statistically significant (AHR = 1.1; 95% CI = 0.3
      4.3). Pediatric motherhood is a risk factor for stillbirth in twin gestation,
      especially, preterm and preterm-SGA stillbirth phenotypes. Prevention of
      stillbirth among this category of mothers should target the period preceding full
      term.

PMID- 17032550
TI  - Stillbirths in multiple births: test of independence.
AB  - The stillbirth rate in twins is a more sensitive indicator of environmental
      hazards than the stillbirth rate in singletons. Medical care or other
      socioeconomic factors may be more influential for perinatal survival in twin than
      in single deliveries. Studies have indicated that stillbirths among children in a
      set of multiple maternities are not independent. Models were considered assuming
      independent outcomes within a set of multiple maternities. Analyses of the
      stillbirth rates confirm that the risk of stillbirth among males is almost
      constantly higher than among females. Any model introduced should assume
      different stillbirth rates for males and females. The models were tested with
      both maximum likelihood and minimum chi2 methods. Data was analyzed from Sweden,
      the Aland Islands, Saxony, England and Wales, and significant discrepancies
      obtained from the independence models. The same-sexed twin data contain both
      monozygotic and dizygotic twin sets with apparently different stillbirth rates.
      Consequently, for same-sexed twins the proposed model could be considered too
      simple. After improvement by splitting the same-sexed data into monozygotic and
      dizygotic twin sets, the dependence still remains. The proportion of both same
      sexed and opposite-sexed twin pairs that contain two stillborn is greater than
      what the stillbirth rates and the independence should indicate. Consequently,
      stillbirth rate estimates based on the relative frequency of twin sets with two
      stillborn children have a positive bias. When the stillbirth rate decreases, the
      number of sets with two stillborn children decreases more slowly than would be
      indicated by independence.

PMID- 17032551
TI  - Outcome of twins delivery; predictors for successful vaginal delivery: a single
      center experience.
AB  - The aim of this study was to compare maternal and neonatal outcome of twin births
      according to mode of delivery and to isolate the factors predicting a successful
      vaginal delivery and those predicting a failed trial of labor (TOL) leading to an
      emergent cesarean section. We reviewed all twin deliveries during the years 1995
      to 2004. Parameters studied include maternal age, parity, gestational age,
      maternal antepartum complications and postpartum complications, fetal
      presentations, birthweight, mode of delivery of each twin, Apgar scores and cord
      pH. During the study period there were 40,710 deliveries of which 804 (1.9%) were
      twin deliveries. Of the 804 twins, 398 (49.5%) had planned cesarean sections
      (PCS) and 406 (50.5%) entered a TOL. Maternal age and parity were similar among
      the groups. Neonatal outcomes and postpartum complications did not differ between
      the groups. Of 406 women who had a TOL, 84.9% eventually delivered both twins
      vaginally. A significantly higher percentage of antepartum complications were
      noted among those who failed the TOL compared to those with successful TOL (8.2%
      vs. 1.7%, p = .01). The number of neonates with pH of less than 7.0 did not
      differ between the groups although more neonates (2.5% vs. 0.4%, p = .05) among
      the failed TOL had an Apgar score of less than 7.0 at 5 minutes compared to
      successful TOL. Vaginal delivery of both twins after TOL occurred in 91% of
      vertex/vertex compared with 71.8% of vertex/nonvertex presenting twins (p < .01).
      Neonatal outcomes did not differ between both groups. Our results indicate that
      both vaginal and PCS are comparable options for vertex presenting first twin
      regardless of second twin presentation.

PMID- 17032552
TI  - Course of ovarian hyperstimulation syndrome in 19 intact twin pregnancies after
      assisted reproduction techniques, with a case report of severe thromboembolism.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted
      reproduction techniques using in vitro fertilization and intracytoplasmic sperm
      injection (IVF/ICSI). Its etiology has still not yet been fully resolved. Human
      chorionic gonadotrophin, administered exogenously as well as produced
      endogenously during pregnancy, is responsible for the onset of OHSS, and high
      levels of estradiol appear to worsen the condition. In this case series, the
      course of mild to severe OHSS was evaluated in 19 intact twin pregnancies after
      IVF/ICSI. Another serious complication associated with OHSS is thromboembolic
      events. In these cases, the pregnancy can be protected through anticoagulation
      treatment, but there may be exceptions to this. This series includes a case of
      bilateral thrombosis of the internal and external jugular veins in the 7th
      gestational week in a twin pregnancy after OHSS and ICSI, with termination of the
      pregnancy in the 9th gestational week due to progressive thrombosis during
      anticoagulation therapy.

PMID- 17032553
TI  - An acephalus acardius amorphous fetus in a monochorionic pregnancy with sex
      discrepancy.
AB  - Acephalus acardia is among the most severe malformations described in fetuses,
      with an incidence of about 1 in 35,000 births and is due to twin-to-twin
      transfusion syndrome, frequently occurring in monochorionic twin pregnancies. The
      severity of the syndrome depends upon the type of the anastomoses arising between
      the vascular networks of the two fetuses, usually configuring the 'twin reverse
      arterial perfusion syndrome'. No clear and univocal etiological explanation is
      known, though few cases with chromosomal abnormalities have been reported so far.
      In some cases the fusion of two or more separate placentae of dizygotic fetuses
      occurs, leading to monochorionic twinning. Few cases of acardius amorphous with
      complete autoptical examination have been described so far. We report a case of
      acephalus acardius amorphus fetus, showing features of extremely severe sistemic
      immaturity with very few structured organs. Defined external and autoptic
      examinations have been performed on the dismorphic twin, along with the
      histological examination of tissue samples. Kariotype analysis showed sex
      discrepancy between the twins, as a normal female kariotype had been detected in
      the acephalus acardius while the living co-twin was a normal healthy male. The
      analysis of the placenta showed the vascular anomalies leading to the twin-to
      twin transfusion syndrome.

PMID- 17032555
TI  - Gastrointestinal stromal tumors: imatinib and beyond.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. Clinicians previously classified GISTs as "benign" or
      "malignant," but now place resected tumors in risk categories that are based on
      size and mitotic rate. Historically, GIST patients were managed with surgery
      alone, as chemotherapy and radiotherapy have minimal activity in this disease. In
      the pre-imatinib era, patients with recurrent or metastatic disease generally did
      very poorly. GIST therapy was revolutionized following the discovery of oncogenic
      mutations in the c-kit gene, as well as in the platelet-derived growth factor
      receptor. Subsequently, it has been confirmed that the KIT receptor tyrosine
      kinase is both a diagnostic marker and a useful therapeutic target in GIST.
      Imatinib, a potent inhibitor of KIT activity, is now standard front-line therapy
      for advanced GIST. With the introduction of imatinib, there have been dramatic
      improvements in response rates, time to progression, and survival. Imatinib is
      now being investigated and shows promise in the neoadjuvant and adjuvant
      settings. Unfortunately, many patients eventually recur or progress during
      imatinib therapy. For these patients, imatinib dose escalation and/or surgical
      evaluation are appropriate. Additionally, a novel tyrosine kinase inhibitor such
      as SU11248 (sunitinib) is a reasonable option for progressive, imatinib-resistant
      disease. With the identification of other downstream pathways, several other
      promising therapies are under current investigation either alone or in
      combination with imatinib and surgery.

PMID- 17032556
TI  - The enigma of desmoid tumors.
AB  - Desmoid tumors (aggressive fibromatosis) are rare neoplastic tumors that may
      occur sporadically or in association with familial adenomatous polyposis (FAP).
      The etiology of these tumors is unknown, but hormonal, genetic, and physical
      factors play a role in their development and growth. A distinction is often made
      between desmoids in patients with FAP and those in patients without FAP, but
      clinically these tumors are treated the same; the only difference is the
      preferential intra-abdominal location of FAP desmoids. The goal of desmoid
      treatment is local control. Choosing the appropriate method for achieving local
      control may be complex as the functional and cosmetic outcomes of each method
      must be considered. In addition, because desmoids spontaneously regress, any
      claim of successful intervention must be viewed skeptically. Local control is
      mainly achieved by surgical intervention and may be improved with the addition of
      radiation therapy (RT). For patients who cannot undergo surgery, the options for
      local control include RT and systemic therapies such as hormones, nonsteroidal
      anti-inflammatory drugs (NSAIDs), interferon, and chemotherapy. Patients with
      symptomatic, progressive disease who can tolerate chemotherapy should be
      presented with the option of low-dose or standard antisarcoma chemotherapy.
      Although it is unclear which regimen is better, patients appear to have quicker
      responses to the standard antisarcoma therapy. Hormone therapy, NSAIDs, and
      interferon are used often, with varying success, and should be reserved for
      minimally symptomatic patients or for patients who do not want or are not
      candidates for chemotherapy. The treatment of desmoid tumors remains an enigma.
      As more options become available, selecting the correct therapy becomes more
      nuanced. Further clinical trials are needed to help the clinician navigate his or
      her way through the morass of desmoid tumor therapies.

PMID- 17032557
TI  - Management of osteosarcoma.
AB  - Improving cure rates for osteosarcoma continues to be a major challenge. The
      clinical management of individual patients is exacting and requires a skilled,
      experienced team including a surgeon, pathologist, oncologist, and radiologist,
      with support from specialist nurses and rehabilitation teams. Outcomes from
      treatment have improved little in 20 years and remain disappointing. Chemotherapy
      for osteosarcoma is among the most grueling of any given for solid tumors, and
      treatment of the primary tumor is associated with permanent disability of some
      degree in a significant proportion of patients. New systemic treatments remain
      beyond the horizon. In recognition of these difficulties, an international
      cooperation has begun with the opening of a randomized trial, European and
      American Osteosarcoma (EURAMOS) 1, in Europe and the United States. This study
      heralds a new era of clinical investigation into osteosarcoma, with the promise
      of valuable biologic insights and rapid evaluation of investigational strategies.
      Osteosarcoma should always be treated under the guidance of a specialist team,
      and we recommend that whenever possible, patients be offered entry into EURAMOS 1
      or other well-designed clinical trials.

PMID- 17032558
TI  - Adjuvant therapy for extremity sarcomas.
AB  - Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy.
      Surgery is the primary treatment for patients with no evidence of metastatic
      disease, and for small low-grade superficial tumors in which adequate margins can
      be obtained, it may be the only therapy indicated. For large, deep tumors or
      tumors that are close to important neurovascular structures or bone, the addition
      of radiotherapy to resection has improved local control and increased limb
      salvage without affecting overall survival. Adjuvant chemotherapy has been an
      issue of considerable debate. Because 50% of patients with high-risk tumors will
      develop metastatic disease, effective systemic treatment with chemotherapy is
      needed. Unfortunately, studies have shown minimal improvement in overall survival
      when chemotherapy is added to the local treatment of high-risk extremity STS.
      More recently, a few trials of neoadjuvant chemotherapy consisting of mesna,
      doxorubicin, ifosfamide, and dacarbazine and high-dose doxorubicin and ifosfamide
      have shown some early promising results, but at the price of increased toxicity.
      Targeted therapy has shown some of its best results with gastrointestinal stromal
      tumors, but so far there has been little success in treating extremity STS. At
      this time, high-dose adjuvant or neoadjuvant chemotherapy should be given in the
      setting of a clinical trial to patients with high-risk tumors who can tolerate a
      potentially toxic chemotherapeutic regimen. The goal of these trials should be to
      assess new combination therapies, possibly including targeted therapies, for the
      management of large high-grade, high-risk soft tissue sarcomas.

PMID- 17032559
TI  - Chemotherapeutic options for primary brain tumors.
AB  - Malignant gliomas are the most common primary brain tumors. Despite intensive
      clinical investigation and many novel therapeutic approaches, treatment for most
      primary brain tumors remains inadequate. Most are associated with a high rate of
      recurrence after primary therapy and a dismal outcome following recurrence.
      Surgery and radiation remain the primary modalities of therapy for malignant
      brain tumors. The role of chemotherapy in malignant gliomas, especially
      glioblastoma multiforme, has been inconclusive. However, a recent trial by the
      European Organisation for Research and Treatment of Cancer and the National
      Cancer Institute of Canada combining radiation therapy with temozolomide for
      newly diagnosed glioblastoma patients showed a significantly improved survival
      benefit over radiation therapy alone. In addition to this encouraging progress,
      recent experience has shown that selected malignant brain tumors--for example,
      anaplastic oligodendrogliomas, primary central nervous system lymphomas,
      medulloblastomas, and intracranial germ cell tumors--are often highly responsive
      to chemotherapy. Molecular genetic studies are becoming indispensable aids in the
      diagnosis and treatment of the malignant gliomas. For example, we have learned
      that allelic loss of chromosome 1p is a significant predictor of
      chemosensitivity, whereas combined loss of chromosomes 1p and 19q is a strong
      predictor of chemosensitivity, progression-free survival, and overall survival in
      patients with anaplastic oligodendroglioma. Similarly, MGMT promoter methylation
      is associated with more frequent responses and longer survival in patients with
      glioblastoma multiforme receiving temozolomide-based therapy. These and other
      recent advances have led to the development and testing of several novel
      chemotherapeutic and molecular-targeted agents. Several different approaches and
      modalities to improve the efficacy of chemotherapy (eg, MGMT promoter
      methylation) are currently under way. Clinical trials implementing angiogenesis
      inhibitors, biologic modifiers, or molecular-targeted therapies are also actively
      being investigated.

PMID- 17032560
TI  - Current therapeutic approaches in patients with brain metastases.
AB  - The development of brain metastases is often viewed as the end stage of a disease
      course and engenders skepticism about the efficacy of treatment. Aggressive
      management of brain metastases is effective in both symptom palliation and the
      prolongation of life. The majority of patients with controlled intracranial
      metastases will expire from systemic disease rather than from recurrence of these
      metastases. Single brain metastases should be treated with surgical resection or
      stereotactic radiosurgery, though it is unclear at this time if one modality is
      more effective than the other. Surgical resection is preferred when a pathologic
      diagnosis is needed, for tumors larger than 3.5 cm, or when immediate tumor mass
      decompression is required. Stereotactic radiosurgery (SRS) should be applied for
      single tumors less than 3.5 cm in surgically inaccessible areas and for patients
      who are not surgical candidates. Small tumors (ie, < 3.5 cm) that cause minimal
      edema and are surgically accessible may be treated with either surgery or SRS.
      There is controversy over whether whole brain radiation therapy (WBRT) can be
      omitted following surgical resection or SRS. Omission of WBRT increases
      intracranial tumor recurrence; however, this has not been correlated with
      decreased survival. Clinicians who choose to omit upfront WBRT are obligated to
      monitor the patient closely for intracranial recurrence, at which time further
      salvage therapy in the form of surgery, SRS, or WBRT may be considered. Histology
      is of particular importance when considering WBRT for patients with
      radioresistant tumors such as melanoma, renal cell carcinoma, or sarcoma. WBRT
      may be of less clinical benefit in this setting. Chemotherapy has been
      demonstrated to improve response rates when used as an adjunct to radiation
      therapy. These improvements in response rates have not been correlated with an
      improvement in median survival. Noncytotoxic radiosensitizing agents such as
      motexafin and efaproxiral show promise. Phase III trials to assess the benefit of
      motexafin in patients with metastatic lung cancer and efaproxiral in patients
      with metastatic breast cancer are ongoing. Targeted therapies offer promise in
      achieving therapeutic efficacy while minimizing side effects. Surgical adjuncts
      such as BCNU (carmustine) wafers and the GliaSite Radiation System (Cytyc
      Corporation, Marlborough, MA) may be useful in the future in achieving optimal
      local tumor control.

PMID- 17032561
TI  - Predictive and prognostic markers in human glioblastomas.
AB  - Glioblastomas (GBMs) are among the most aggressive of all known human tumors. The
      median survival times remain in the 12- to 15-month range despite aggressive
      surgery, radiation, and chemotherapy. Through molecular and genetic profiling
      efforts, underlying mechanisms of resistance to these therapies are becoming
      better understood. The present standard of care has been shaped by the recently
      reported phase III study by the European Organisation for Research and Treatment
      of Cancer and the National Cancer Institute of Canada, which found that the
      addition of temozolomide (TMZ) to radiation therapy significantly improved
      outcome compared with radiation alone. However, careful examination of these data
      reveals that not all GBM patients benefited from the addition of TMZ to radiation
      therapy. A companion correlative study found that GBM patients with tumors with
      MGMT promoter methylation appeared to derive the greatest benefit from the
      addition of TMZ to radiation therapy. Although this finding is provocative, it
      should be kept in mind that this study was performed retrospectively and that
      prospective validation is required before MGMT methylation can be used for
      clinical stratification purposes. However, this study does show promise for the
      tailoring of future treatments according to the molecular and genetic profiles of
      an individual's tumor rather than using the "one-glove-fits-all" approach that is
      currently being followed. As more effective "smart drugs" are developed,
      molecular and genetic profiling will assume even greater importance in this
      regard.

PMID- 17032562
TI  - Management of pineal region tumors.
AB  - Tumors of the pineal region represent a diverse collection of tumors with a
      variety of natural histories. This diversity necessitates accurate histologic
      diagnosis to allow rational therapeutic planning. Evaluation of a pineal lesion
      should begin with craniospinal MRI and analysis of the cerebrospinal fluid (CSF).
      Whereas certainty of the histologic diagnosis is now a requirement for treatment
      in Western nations, some Asian centers continue to recommend a test dose of
      radiation therapy based on the high incidence of germinoma in those countries. If
      there is high clinical suspicion of a germinoma or tectal glioma, stereotactic or
      endoscopic biopsy may be pursued. All other lesions should be referred for open
      biopsy with microsurgical techniques. This approach provides adequate tissue for
      diagnosis, may be curative in low-grade tumors, and may substantially improve
      survival in patients with malignant tumors. If open surgery is not desired by the
      patient or practitioner, stereotactic or endoscopic biopsy may be followed by
      radiosurgery for localized, well-demarcated tumors. Radiation therapy is the
      first-line therapy for germinomas. Although the optimal radiation dosage and
      volume have not been decided, the current Children's Oncology Group trial may
      offer definitive evidence to address this dilemma in germ cell tumors. Evidence
      of CSF seeding requires craniospinal radiation and adjuvant chemotherapy
      regardless of tumor type. Diagnosis of any of the malignant tumors (non-germ cell
      tumors, pineoblastomas, and parenchymal tumors of intermediate determination)
      also requires craniospinal radiation (with local tumor doses of at least 50 Gy)
      and adjuvant chemotherapy (generally platinum based). Patients with tectal
      gliomas may undergo excision with or without postoperative radiation; however,
      they also may be observed with vigilant follow-up alone.

PMID- 17032563
TI  - Managing the cognitive effects of brain tumor radiation therapy.
AB  - Postoperative radiation therapy (RT), either alone or in combination with
      chemotherapy, is the mainstay of treatment for primary and/or metastatic brain
      tumors. The majority of patients with brain tumors will have significant symptoms
      of their disease and of RT that will have a negative impact on their quality of
      life and neurocognitive function. The symptoms of brain tumors depend on tumor
      location. Radiation-induced brain injury is a complex and dynamic process
      involving all cells in the brain, including endothelial and oligodendroglial
      cells, astrocytes, microglia, neurons, and neuronal stem cells. The symptoms of
      radiation-induced brain injury may be acute, subacute, or chronic, occurring
      hours, days, weeks, months, and even years after exposure to radiation, the
      pathogenesis of which is oxidative stress and inflammation. At present, there are
      no effective preventive approaches for radiation-induced brain injury. Rather,
      the management of radiation-induced fatigue, changes in mood, and cognitive
      dysfunction involves a multidisciplinary approach using pharmacologic,
      behavioral, and rehabilitative therapies. Given the prevalence of brain neoplasms
      and the high incidence of the radiation-induced symptom cluster and brain injury,
      clinical research to address these important clinical problems is critical.

PMID- 17032564
TI  - Diagnosis and treatment of neurotransmitter disorders.
AB  - The neurotransmitter disorders represent an enigmatic and enlarging group of
      neurometabolic conditions caused by abnormal neurotransmitter metabolism or
      transport. A high index of clinical suspicion is important, given the
      availability of therapeutic strategies. This article covers disorders of
      monoamine (catecholamine and serotonin) synthesis, glycine catabolism, pyridoxine
      dependency, and gamma-aminobutyric acid (GABA) metabolism. The technological
      aspects of appropriate cerebrospinal fluid (CSF) collection, shipment, study, and
      interpretation merit special consideration. Diagnosis of disorders of monoamines
      requires analysis of CSF homovanillic acid, 5-hydroxyindoleacetic acid, ortho
      methyldopa, BH4, and neopterin. The delineation of new disorders with important
      therapeutic implications, such as cerebral folate deficiency and PNPO deficiency,
      serves to highlight the value of measuring CSF neurotransmitter precursors and
      metabolites. The impressive responsiveness of Segawa fluctuating dystonia to
      levodopa is a hallmark feature of previously unrecognized neurologic morbidity
      becoming treatable at any age. Aromatic amino acid decarboxylase and tyrosine
      hydroxylase deficiency have more severe phenotypes and show variable
      responsiveness to levodopa. Glycine encephalopathy usually has a poor outcome;
      benzoate therapy may be helpful in less affected cases. Pyridoxine-dependent
      seizures are a refractory but treatable group of neonatal and infantile seizures;
      rare cases require pyridoxal-5-phosphate. Succinic semialdehyde dehydrogenase
      deficiency is relatively common in comparison to the remainder of this group of
      disorders. Treatment directed at the metabolic defect with vigabatrin has been
      disappointing, and multiple therapies are targeted toward specific but protean
      symptoms. Other disorders of GABA metabolism, as is true of the wide spectrum of
      neurotransmitter disorders, will require increasing use of CSF analysis for
      diagnosis, and ultimately, treatment.

PMID- 17032565
TI  - Pediatric headache.
AB  - Migraine is very treatable in children and adolescents. Principles of treatment
      include early intervention, elimination of triggers, involvement of parents and
      schools, and judicious use of medicines. Although there is no pediatric
      indication in the United States, triptans are safe and effective in this age
      group. Prophylactic drugs should be used when significant disability from
      migraine exists. Choice of drug is based upon comorbidity. Nonpharmacologic
      treatment has an important role.

PMID- 17032566
TI  - Treatment of infantile spasms.
AB  - Infantile spasms are associated with a diverse range of conditions, and treatment
      options are available. However, outcomes remain generally poor, particularly for
      those with symptomatic etiologies. First-line therapy is considered to be
      hormonal (adrenocorticotropic hormone; ACTH), which some evidence suggests is
      more effective when started early. However, side effects may place limits on its
      use acutely and long-term. There is additional evidence for vigabatrin,
      specifically for infantile spasms secondary to tuberous sclerosis complex. In
      refractory cases, candidacy for surgical management should be explored, along
      with new-generation anticonvulsants (eg, topiramate, zonisamide) and the
      ketogenic diet. There is urgent need for further treatment trials comparing
      anticonvulsants with ACTH and a satisfactory animal model for the study of
      spasms.

PMID- 17032567
TI  - New treatments for tic disorders.
AB  - Tics vary in severity from infrequent and barely noticeable to nearly continuous
      and highly disruptive. Treatment of tic disorders depends on the severity of the
      tics, the distress they cause, and the effects they have on school, work, or
      daily activities. Many tics do not interfere with school or everyday life and do
      not require specific treatment. Comorbid disorders such as attention deficit
      hyperactivity disorder, anxiety, and obsessive-compulsive disorder occur in more
      than 50% of patients. The associated comorbidity can be more bothersome than the
      tics themselves. Treatment should be aimed at the most troubling symptom.
      Education and reassurance are often sufficient for mild and occasional tics. For
      tics of moderate severity, clonidine and guanfacine have a reasonable safety
      profile. They are considered as first-line medications. With clonidine, start
      with 0.05 mg at bedtime. Increase as needed and as tolerated by 0.05 mg every 4
      to 7 days to a maximum dosage of 0.3 to 0.4 mg/day divided three or four times a
      day. With guanfacine, start with 0.5 mg at bedtime. The dosage may be increased
      as needed and as tolerated by 0.5 mg every week to a maximum dosage of 3 to 4
      mg/day, divided twice a day. There are emerging data that behavioral therapy is
      effective for treatment of tics in some individuals. Dopamine receptor blockers
      are the most potent medications for treating severe tics. The efficacy appears to
      be proportionate to the affinity for dopamine D2 receptors. Thus, standard
      antipsychotic medications such as haloperidol, pimozide, or fluphenazine are the
      most potent. However, these medications commonly cause bothersome side effects.
      Therefore, we recommend use of atypical neuroleptics before standard neuroleptics
      in most patients. Risperidone is usually the first choice and may have efficacy
      for behavior problems that often accompany tics. Start with 0.01 mg/kg/dose once
      a day; dosage may be increased by 0.02 mg/kg/day at weekly intervals, up to 0.06
      mg/kg/dose once a day. Ziprasidone and olanzapine are reasonable alternatives.

PMID- 17032568
TI  - Management of arterial hypertension in patients with acute stroke.
AB  - Management of arterial hypertension in the hyperacute period immediately after
      stroke ictus remains controversial. Extremes of blood pressure (BP) are
      associated with poor outcomes in all stroke subtypes. Severely hypertensive
      patients likely benefit from modest BP reductions, but aggressive BP reduction
      may worsen outcome. Although little evidence is currently available to
      definitively establish guideline recommendations for optimal BP goals at stroke
      presentation, recently published research is shedding some light on how to
      approach management of BP after stroke. Antihypertensive treatment should
      probably be deferred in ischemic stroke patients except in cases of severe
      hypertension or when thrombolytic therapy is warranted and the patient's BP is
      above acceptable levels. Hypertensive hemorrhagic stroke patients may benefit
      from modest BP reductions. Relative hypotension causing regional hypoperfusion is
      an increasingly understood concept immediately following ischemic or hemorrhagic
      stroke, emphasizing the need for careful titration of appropriate medications to
      minimize fluctuations in BP for treated patients. Ongoing trials will improve our
      current knowledge regarding BP management after ischemic and hemorrhagic stroke.

PMID- 17032569
TI  - Update on the management of hypertension to prevent stroke.
AB  - Hypertension is the leading modifiable risk factor for stroke, including first
      ever and recurrent stroke. The association between blood pressure (BP) and stroke
      risk is continuous and may be documented as low as 115/75 mm Hg. Because of this
      continuum of risk, and because most strokes occur in individuals with mild
      hypertension or even normal BP values, we are now beginning to recognize
      "prehypertension" as a stage in which early recognition and intervention may
      confer benefit. In addition to increased risk for ischemic and hemorrhagic
      stroke, hypertension may be associated with increased risk of cognitive
      impairment. Reductions in BP are reliably associated with reduced stroke risk.
      Some evidence suggests that certain agents, including angiotensin-converting
      enzyme inhibitors and angiotensin receptor blockers, may have protective effects
      beyond BP lowering. Overall, the degree of BP lowering is key, and therefore most
      classes of BP-lowering agents may be recommended at this point. Many patients
      with hypertension will require more than one BP-lowering agent to control BP.
      Lifestyle modification is appropriate at all levels of intervention. Further
      studies are needed to ascertain the mechanisms of benefit of different classes of
      antihypertensive agents in the reduction of stroke and cardiovascular disease
      risk.

PMID- 17032570
TI  - Cholesterol lowering to prevent stroke: who, when, and how?
AB  - The epidemiologic link between increased low-density-lipoprotein (LDL)
      cholesterol and ischemic stroke is controversial. However, recent trials make it
      clear that LDL reduction by statin agents in high-risk patients reduces the risk
      of ischemic stroke. The risk of first stroke is reduced within 1 to 2 years of
      statin therapy in patients at high risk for ischemic vascular disease. Patients
      with any history of cerebrovascular disease who are treated with statins have a
      reduced risk of coronary ischemic events and of all major vascular ischemic
      events, independent of any history of coexisting coronary artery disease. In
      particular, patients with recent transient ischemic attack or ischemic stroke
      show significantly reduced risks of both recurrent stroke and coronary events
      when they are treated with high-dose statin therapy. Most patients with ischemic
      cerebrovascular disease should be placed on statin drugs. However, most stroke
      patients are not currently treated to recommended levels with these agents,
      providing ample room for improvement in physician performance.

PMID- 17032571
TI  - Treatment and prevention of stroke in children with sickle cell disease.
AB  - Stroke is one of the major complications in children with sickle cell disease
      (SCD). Ischemic stroke is associated with small asymptomatic subcortical infarcts
      to large territorial lesions causing major disability. Intracranial hemorrhages
      may be caused by aneurysm rupture or by leakage from moyamoya vessels or venous
      sources. There have been no acute stroke treatment studies in SCD, but hydration
      and exchange transfusion are often recommended. However, there is an evidence
      base for primary and to some extent secondary stroke prevention. Primary
      prevention of stroke was demonstrated in the Stroke Prevention Trial in Sickle
      Cell Anemia (STOP), in which children with transcranial Doppler (TCD) mean blood
      flow velocities of 200 cm/second (previously shown to indicate high stroke risk)
      or higher were randomized to either regular blood transfusions or no transfusion.
      The study showed a very significant 90% reduction in first stroke with
      transfusion. In STOP2, discontinuing transfusions after 30 months or more (even
      with normal TCD) resulted in a high rate of reversion to abnormal TCD values and
      stroke. TCD screening of all children with SCD, and initiation and maintenance of
      chronic transfusion to maintain hemoglobin S below 30% in the high-risk group, is
      the only proven prevention strategy for stroke in SCD. Hydroxyurea is being
      studied as secondary stroke prevention at this time. No recommendation specific
      to SCD regarding the use of antiplatelet agents or anticoagulants in ischemic
      stroke can be made. Bone marrow transplantation can be curative for SCD, and
      limited data support its use to prevent stroke in SCD.

PMID- 17032572
TI  - Interactions between migraine and stroke.
AB  - When a patient with migraine has a stroke, all other causes of stroke should be
      ruled out before the stroke is attributed to migraine. Migraine mimics that
      present with headaches and stroke, including arteriovenous malformation and
      cervical carotid artery dissection, should be considered. Patent foramen ovale is
      a risk factor for both migraine and stroke and should be ruled out with
      transesophageal echocardiography. A patient with migraine with aura with
      persistent focal neurologic deficits in the distribution of the typical aura can
      be diagnosed with migrainous stroke. Patients with migraine with aura with
      persistent focal neurologic deficits can be treated pharmacologically with
      intravenous verapamil or magnesium sulfate to relieve the symptoms in familial
      hemiplegic migraine and sporadic hemiplegic migraine. Prophylactic treatment
      should be administered to patients with frequent attacks of migraine with aura to
      prevent recurrence. Oral verapamil is recommended for patients with familial
      hemiplegic migraine and may be effective in patients with sporadic hemiplegic
      migraine. Endovascular closure of patent foramen ovale has been reported to
      prevent recurrence of migraine with aura. The role of patent foramen ovale
      closure remains controversial pending completion of controlled randomized trials.

PMID- 17032573
TI  - Evolving trends in medical care-coordination for patients with HIV and AIDS.
AB  - HIV/AIDS is a condition characterized by a variety of medical and social needs
      that affect individuals over time. System-level problems of access, rising costs
      of care, and varying quality of HIV/AIDS care in addition to the individual
      barriers to care such as stigma, perceived discrimination, competing needs, and
      co-morbid conditions have highlighted the importance of using comprehensive
      approaches to care delivery. Several types of services have been proposed to
      improve care coordination for various diseases, including case management,
      community health workers, promotoras, and patient navigators. In this paper, we
      will review the characteristics of care coordination interventions for persons
      with HIV and the findings in the literature about their association with HIV
      health outcomes. We will conclude with a discussion of the implications and
      important areas for further investigations on this topic.

PMID- 17032574
TI  - Contingency management interventions for HIV-related behaviors.
AB  - Contingency management (CM) is a scientifically based treatment approach
      typically employed in substance abuse treatment settings to reinforce drug
      abstinence, counseling attendance, completion of activities, or other treatment
      goals. Although the application of CM to HIV management has few published
      studies, it shows promise as an intervention for HIV-related behaviors. CM
      interventions such as voucher reinforcement, prize systems, and cash incentives
      can be used to reduce HIV risk behaviors and to improve HIV medication adherence.
      CM programs have wide applicability to HIV prevention and management in clinical
      and community settings and can be implemented as stand-alone techniques or in
      combination with other interventions.

PMID- 17032575
TI  - Approaching "HIV elimination": interventions for acute HIV infection.
AB  - Recent observations from several groups suggest that individuals with acute
      (antibody negative) HIV infections (AHI) may present for "routine" HIV testing in
      unanticipated numbers. Most of these papers have highlighted the use of group
      testing strategies to screen antibody negative testing sera for HIV RNA using
      nucleic acid amplification tests. At the same time, accumulating evidence
      indicates that AHI is a time of briefly, but substantially elevated risk for
      transmission of HIV. In this paper, we review these new data with attention to
      their implications for HIV prevention strategies. By calling attention to a
      subset of patients that are both recently infected and at transiently very high
      risk of transmitting their new infection to partners, AHI detection makes it
      possible to use traditional, network notification-based public health strategies
      effectively in the fight against HIV.

PMID- 17032576
TI  - Rapid HIV testing: a review of the literature and implications for the clinician.
AB  - HIV counseling and testing services are critical for individuals to access HIV
      prevention and treatment. Unfortunately, the standard HIV testing algorithm is
      complex and includes the use of a sensitive enzyme immunoassay (EIA), followed by
      a Western blot if the EIA is positive. This process can take 1 week or longer.
      Therefore, innovative approaches that incorporate simpler diagnostic algorithms
      are needed to reach the large number of individuals who are not aware that they
      are HIV-infected. Currently available rapid HIV tests have demonstrated
      sensitivities and specificities comparable to those of standard HIV testing
      without the requirements of sophisticated laboratory resources or highly trained
      personnel. These rapid HIV tests are increasingly being used in various clinical
      scenarios to decrease the number of missed opportunities for detection of HIV
      infection. Their use is particularly applicable in specific clinical and
      nonclinical settings; public health settings; labor and delivery wards; in the
      management of occupational exposures; and in resource-constrained settings. The
      overarching goals of achieving wide implementation of rapid HIV tests are to
      increase the number of individuals who are aware of their serostatus, to improve
      entry of persons with HIV into prevention and care services, and to prevent
      further HIV transmission.

PMID- 17032577
TI  - Psychiatric behavioral aspects of comanagement of hepatitis C virus and HIV.
AB  - Coinfection with HIV hastens the progression of liver disease in persons with
      hepatitis C virus (HCV) infection. As mortality directly due to HIV continues to
      decrease among persons who are HIV-positive, coinfection with HCV has emerged as
      a leading cause of death. There is increasing attention to the need to actively
      treat HCV infection in HIV/HCV coinfected patients. Current HCV treatment with
      pegylated interferon and ribavirin achieves sustained viral response in up to 40%
      of coinfected patients but has numerous neuropsychiatric side effects. Providers
      are hesitant to begin HCV treatment in the coinfected population given the high
      prevalence of existing psychiatric illness, cognitive impairment, and substance
      use disorders. There is an urgent need for research into the psychiatric and
      behavioral predictors of HCV treatment adherence and virologic outcome, as well
      as into the optimal psychiatric management of the neuropsychiatric sequelae of
      HCV therapy.

PMID- 17032578
TI  - Extending HIV care in resource-limited settings.
AB  - Despite the clear benefits of antiretroviral therapy (ART), only three countries
      in sub-Saharan Africa have achieved the "3 by 5" goal of treating at least half
      of the persons living with HIV/AIDS who need it. A major obstacle faced by many
      lower income countries is the establishment of treatment programs in rural areas
      where there is a scarcity of trained health care providers and infrastructure.
      This paper reviews published data on rural ART programs in lower income countries
      to identify necessary components of such a program. No clearly superior model for
      rural ART delivery has emerged. All programs document the need for expanded
      physical infrastructure, laboratory development, recruitment/training of
      additional health care providers, and/or the introduction of new technologies in
      order to effectively support the needs of ART roll-out.

PMID- 17032580
TI  - Society for Reproductive Biology Founders' Lecture 2006 - life in the pouch: womb
      with a view.
AB  - Marsupials give birth to an undeveloped altricial young after a relatively short
      gestation period, but have a long and sophisticated lactation with the young
      usually developing in a pouch. Their viviparous mode of reproduction trades
      placentation for lactation, exchanging the umbilical cord for the teat. The
      special adaptations that marsupials have developed provide us with unique
      insights into the evolution of all mammalian reproduction. Marsupials hold many
      mammalian reproductive 'records', for example they have the shortest known
      gestation but the longest embryonic diapause, the smallest neonate but the
      longest sperm. They have contributed to our knowledge of many mammalian
      reproductive events including embryonic diapause and development, birth
      behaviour, sex determination, sexual differentiation, lactation and seasonal
      breeding. Because marsupials have been genetically isolated from eutherian
      mammals for over 125 million years, sequencing of the genome of two marsupial
      species has made comparative genomic biology an exciting and important new area
      of investigation. This review will show how the study of marsupials has widened
      our understanding of mammalian reproduction and development, highlighting some
      mechanisms that are so fundamental that they are shared by all today's marsupial
      and eutherian mammals.

PMID- 17032581
TI  - Reproduction in female swamp wallabies, Wallabia bicolor.
AB  - The swamp wallaby (Wallabia bicolor) is a common, medium-sized, browsing
      macropodid marsupial that is unique in many ways. Relatively little is known
      about the reproductive biology of this species. Previous studies have proposed
      that the swamp wallaby has a pre-partum oestrus because the gestation period (x =
      35.5 days, n = 4) is on average longer than the oestrus period (x = 31.0 days, n
      = 5) and the period from the removal of pouch young (RPY) to mating (x = 26.0
      days, n = 3). In the current study, the period from RPY to birth was confirmed at
      x = 31.25 days (n = 4) in captive animals, consistent with a pre-partum oestrus.
      A growth curve for swamp wallaby pouch young was constructed from the progeny of
      captive animals to estimate the age and date of birth of young in a wild, culled
      population in South Gippsland, Victoria, and the reproduction of females in the
      wild throughout the year was examined. Young were born in every month of the
      year, with no statistically significant variation in the number of young born in
      each month. Females did not have a period of seasonal anoestrus and conceived
      throughout the year. Female swamp wallabies in South Gippsland bred continuously
      throughout the period of this study.

PMID- 17032579
TI  - The potential impact of antiretroviral therapy on fertility in sub-Saharan
      Africa.
AB  - Approximately 14 million women of child-bearing age are living with HIV/AIDS in
      sub-Saharan Africa. Women with HIV infection have between 25% and 40% lower
      fertility than noninfected women. As antiretroviral (ARV) therapy becomes
      increasingly accessible in sub-Saharan Africa, it is important to understand
      whether and how the associated clinical improvements correspond with changes in
      the incidence of pregnancy and fertility. Accordingly, this paper reviews the
      literature on the potential impact of ARV therapy on the fertility of women with
      HIV infection in sub-Saharan Africa. We use Bongaarts' proximate determinants of
      fertility framework (adapted for conditions of a generalized HIV epidemic) to
      examine the underlying mechanisms through which use of ARV therapy may impact the
      fertility of women with HIV infection. A conceptual framework is proposed to
      guide future research aimed at understanding how widespread use of ARV therapy
      may impact fertility in sub-Saharan Africa.

PMID- 17032582
TI  - Oestrous behaviour and development of preovulatory follicles in goats induced to
      ovulate using the male effect with and without progesterone priming.
AB  - The objective of the current study was to examine follicular dynamics in goats
      induced to ovulate by using the male effect with or without progesterone
      pretreatment. Ten Murcian-Granadina goats were treated with a single dose of 25
      mg of progesterone in olive oil on the day of male effect induction (Day 0),
      whereas ten does remained untreated. Changes in the ovarian follicular population
      and onset of oestrous behaviour were checked daily from Day 0 to the day on which
      ovulation was detected by ultrasonography. All of the treated goats and only 20%
      of control goats (P < 0.001) showed oestrous behaviour between 72 and 96 h after
      the introduction of bucks. Differences in follicle growth were found between the
      groups. The control goats exhibiting oestrous behaviour during the first 4 days
      of ovarian screening and all of the goats treated with progesterone had their
      preovulatory follicles in growing phase. However, the largest follicles in
      control does not showing oestrus in these first 4 days were in regressing phase,
      being necessary for the emergence of new preovulatory follicles from a new
      follicular wave between Days 6 and 7, for exhibition of oestrous behaviour and
      subsequent ovulation. In conclusion, the appearance of short luteal phases and
      delayed ovulation in goats treated with the male effect during seasonal
      anoestrous depends on the stage of follicle development at the time of buck
      introduction. A single injection of progesterone stimulates the emergence of a
      new follicular wave, able to grow and give adequate ovulation after induction of
      the male effect.

PMID- 17032583
TI  - Similarities between female meadow voles mating during post-partum oestrus and
      raising two concurrent litters and females raising only one litter.
AB  - In many species of small mammals, females undergo post-partum oestrus soon after
      delivering a litter, becoming pregnant while suckling the previous litter.
      Females raising two concurrent litters need to allocate many more resources to
      reproduction than females raising only one litter. Consequently, there may be
      differences between litters raised concurrently or singly. We investigated this
      issue in the meadow vole, Microtus pennsylvanicus, a species in which most
      females in the wild reproduce during post-partum oestrus. Specifically, we tested
      the hypothesis that the development of pups in two concurrent litters differs
      from that of pups in a single litter. To test this hypothesis, we measured the
      following variables for concurrent and singly reared litters: gestation length;
      litter size; sex ratio; bodyweight of males and females at different ages; total
      litter weight at weaning; growth rates; and intra-litter variation in body mass.
      Except for bodyweight of males at 60 days of age, which was higher in the first
      of the concurrent litters, none of the variables differed among the litters.
      These results indicate that females are able to adjust to differing loads of
      maternal care to provide equivalent resources to concurrent litters and singly
      reared litters.

PMID- 17032584
TI  - Regulation of protein tyrosine phosphatase 4a1, B-cell translocation gene 2,
      nuclear receptor subfamily 4a1 and diacylglycerol O-acyltransferase 1 by follicle
      stimulating hormone in the rat ovary.
AB  - Ovarian response to follicle stimulating hormone (FSH) and luteinising hormone
      (LH) leads to the formation of a mature follicle that is eventually ovulated. FSH
      and LH are essential for this process because they direct changes in somatic
      cells associated with folliculogenesis by regulating the expression of multiple
      genes. We hypothesised that genes induced by FSH in rat Sertoli cells would also
      show hormonal regulation during rat folliculogenesis. The objective of this study
      was to determine the expression patterns of diacylglycerol O-acyltransferase 1
      (Dgat1), nuclear receptor subfamily 4a1 (Nr4a1), an anti-proliferative gene
      (Btg2) and a protein tyrosine phosphatase (Ptp4a1) in the ovaries of pregnant
      mare serum gonadotrophin (PMSG)-treated and human chorionic gonadotrophin (hCG)
      treated rats. Expression of Dgat1, Nr4a1 and Ptp4a1 was induced in ovaries 4 h
      post PMSG treatment. When rats were treated with hCG, Dgat1, Nr4a1 and Ptp4a1
      expression was induced by 12 h. Expression of Nr4a1 protein increases 12-24 h
      after induction of gene expression. Nr4a1 protein was observed in the granulosa,
      theca and luteal cells post PMSG and hCG treatment. These findings should
      increase our knowledge of mechanisms regulating folliculogenesis and
      luteinisation and demonstrate the diverse proteins that are important in ovarian
      function.

PMID- 17032585
TI  - Giant panda (Ailuropoda melanoleuca) spermatozoon decondensation in vitro is not
      compromised by cryopreservation.
AB  - Natural breeding of giant pandas in captivity is compromised, making artificial
      insemination and spermatozoa cryopreservation essential for genetic management.
      This study examined the influence of freeze-thawing on traditional parameters
      such as motility and spermatozoon functionality, specifically decondensation in
      vitro. Giant panda spermatozoa were assessed before and after rapid
      cryopreservation (4 degrees C to -130 degrees C over 2 min) in liquid nitrogen
      vapour. Spermatozoa pre-incubated in medium for 6 h were co-incubated with cat
      zonae (2 zonae microL(-1)) for 30 min to effect capacitation and an acrosome
      reaction. Spermatozoa were then mixed with mature cat oocyte cytoplasm (2
      cytoplasm microL(-1)) for 4 h and evaluated for decondensation. Frozen
      spermatozoa were less motile (P < 0.05) than fresh counterparts immediately post
      thawing, but not after 6 h incubation. There were more (P < 0.05) spermatozoa
      with completely diffused chromatin post-thaw (10.4 +/- 1.3%; mean +/- s.e.m.)
      compared to fresh counterparts (5.1 +/- 1.0%). However, there was no overall
      difference (P > 0.05) in the incidence of decondensation between fresh (4 h, 69.8
      +/- 5.9%) and thawed (4 h, 71.5 +/- 4.9%) spermatozoa after exposure to cat
      oocyte cytoplasm. It is concluded that the 'rapid' method now used to
      cryopreserve giant panda spermatozoa has little impact on spermatozoon
      decondensation.

PMID- 17032586
TI  - Comparison of protocols for cryopreservation of rhesus monkey spermatozoa by post
      thaw motility recovery and hyperactivation.
AB  - Cryopreservation of spermatozoa is useful for gene banking and for in vitro
      fertilisation (IVF). This study compared several published cryopreservation
      techniques to find the most efficient for rhesus macaques. Effectiveness was
      assessed by sperm longevity (post-thaw motility % and duration) and ability to
      hyperactivate in response to chemical activators (caffeine, dibutyryl cyclic
      AMP). Each ejaculate from three males was treated with four published
      cryopreservation protocols (Seier et al. 1993; Sanchez-Partida et al. 2000; Si et
      al. 2000; Isachenko et al. 2005). Upon thawing, each sub-sample was incubated
      either at 37 degrees C in 5% CO2 in air with or without activators or at
      approximately 22 degrees C in atmospheric air without activators for 0-24 h.
      Samples cryopreserved using one method showed zero motility and were not included
      in the 2 ;2 G-test statistical analysis. The other methods all demonstrated good
      immediate post-thaw motility rates (68%, 73% and 62% respectively) and underwent
      capacitation after exposure to activators. Sperm motility in each treatment
      decreased over time at both temperatures but overall, incubation at 22 degrees C
      preserved motility better in all three methods. In summary, cryopreservation of
      rhesus spermatozoa using the method published by Sanchez-Partida et al. or Seier
      et al. appeared best, potentially supporting gene banking as well as allowing for
      multiple IVF uses from the same sample.

PMID- 17032587
TI  - Sperm DNA damage is related to field fertility of semen from young Norwegian Red
      bulls.
AB  - Flow cytometry was utilised for the first time to independently measure five
      sperm parameters of individual spermatozoa of bull ejaculates to differentiate
      between outcome successes after artificial insemination (AI). These parameters
      included plasma membrane and acrosome integrity, mitochondrial functionality and
      DNA damage measured by sperm chromatin structure assay (SCSA) and terminal
      deoxynucleotide transferase-mediated dUTP nick end labelling (TUNEL) assays. For
      each parameter, results of 142 ejaculates (30 bulls) were ranked into three
      groups according to their flow cytometric measures: (1) ejaculates with the 25%
      lowest measures; (2) the 50% middle measures; and (3) the 25% highest measures.
      In total, 20 272 first-service inseminations (18 ;10(6) spermatozoa per AI dose)
      were performed, where fertility was defined as non-return within 60 days after
      first insemination. While plasma membrane and acrosome integrity, and
      mitochondrial functionality were not significantly related to fertility, data
      from SCSA and TUNEL assays were significantly associated with fertility.
      Ejaculates in SCSA group 1 had higher odds of AI success (1.07, 95% CI = 1.02
      1.12), whereas those in group 3 had lower odds of AI success (0.94, 95% CI = 0.89
      0.99), compared with the average odds of all three groups. Ejaculates in group 2
      did not have significantly higher odds of AI success compared with the average
      odds. For TUNEL-positive spermatozoa, the odds of AI success was higher in group
      1 compared with the average odds (1.10, 95% CI = 1.02-1.13), whereas odds of AI
      success in groups 2 and 3 were not significant compared with the average odds. In
      conclusion, despite the high number of spermatozoa per AI dose from high-quality
      bulls, both SCSA and TUNEL assays were valuable measures in this study for
      evaluating sperm quality in relation to fertility after AI.

PMID- 17032588
TI  - Effects of amino acid supplements and replacement of polyvinyl alcohol with
      bovine serum albumin in porcine zygote medium.
AB  - The effects of glutamine, hypotaurine, taurine and premixed solutions of
      essential amino acids (EAA) and non-essential amino acids (NEAA) on in vitro
      development of porcine zygotes were evaluated. The effects of refreshing the
      medium and replacing polyvinyl alcohol (PVA) with bovine serum albumin (BSA) on
      embryonic development were also investigated. Porcine zygotes produced by in
      vitro maturation (IVM) and in vitro fertilisation (IVF) were cultured in porcine
      zygote medium (PZM), as the basal culture medium, for 5 days after IVF. The total
      number of cells in blastocysts was significantly increased by the addition of 2
      mm glutamine to PZM, as was blastocyst yields after supplementation with 0.25 to
      4 mm glutamine. Addition of 1.25 to 10 mm hypotaurine to PZM significantly
      increased blastocyst yields. Addition of 5 mm taurine to PZM significantly
      increased blastocyst yield, whereas taurine had no effect on blastocyst yield in
      cultures already containing 5 mm hypotaurine. Adding 1 x EAA significantly
      increased the rate of blastocyst formation compared with no or 2 x EAA, whereas 2
      x NEAA significantly increased the total cell numbers in blastocysts compared
      with no NEAA. Refreshing the medium at Day 3 had no effect on blastocyst yields,
      whereas medium change significantly reduced the total cell numbers in
      blastocysts. Adjusting the amino acid concentrations of a chemically defined
      medium can improve the developmental competence of porcine embryo.

PMID- 17032589
TI  - Variation of sperm head shape and tail length in a species of Australian
      hydromyine rodent: the spinifex hopping mouse, Notomys alexis.
AB  - In Australia, there are around 60 species of murid rodents that occur in the
      subfamily Hydromyinae, most of which produce highly complex, monomorphic,
      spermatozoa in which the head has an apical hook together with two ventral
      processes containing filamentous actin and a long tail of species-specific
      length. One of the few exceptions to this is the spinifex hopping mouse, Notomys
      alexis, whose spermatozoa have previously been shown to have pleiomorphic heads.
      In this study, the structural organisation of the sperm head has been
      investigated in more detail and the variability in length of the midpiece and
      total length of the sperm tail has been determined for this species. The findings
      confirm that pleiomorphic sperm heads are invariably present in these animals and
      that this variability is associated with that of the nucleus, although nuclear
      vacuoles were not evident. The total length of the sperm tail, as well as that of
      the midpiece, was also highly variable both within, as well as between,
      individual animals. The reason(s) for this high degree of variability in sperm
      morphology is not known but it may relate to a relaxation of the genetic control
      of sperm form owing to depressed levels of inter-male sperm competition.

PMID- 17032590
TI  - [Not just another kinase. New knowledge about myeloproliferative disease].

PMID- 17032591
TI  - [New molecular markers within the chronic myeloproliferative disorders. I: the
      PRV-1 gene].
AB  - PRV-1 is a new molecular marker within the Ph-negative chronic myeloproliferative
      disorders. PRV-1 is a useful, highly sensitive and specific marker in the
      differentiation between polycythaemia vera (PV) and secondary erythrocytosis
      (ET), and seems to identify those PV patients presenting in the early phase of
      the disease with dominating thrombocytosis and thus a clinical phenotype of ET.
      These PRV-1 positive ET patients can be regarded as having "masked" PV or, more
      accurately, as having early PV. Moreover, PRV-1 positivity may be associated with
      a particular risk of thromboembolic complications. The biological role of PRV-1
      and the significance of alterations in PRV-1 gene expression levels during
      treatment remain to be clarified.

PMID- 17032592
TI  - [New molecular markers within the chronic myeloproliferative disorders. II: the
      JAK2 mutation].
AB  - The Philadelphia-negative chronic myeloproliferative disorders feature autonomous
      myeloid hyperproliferation and hypersensitivity to a number of growth factors,
      which most recently have been shown to be explained by a guanine-to-thymidine
      mutation in the Janus tyrosine kinase (JAK2) gene, implicating that phenylalanine
      is substituted with valine in position 617 (V617F mutation). JAK2 is of
      particular importance to haematopoiesis, since JAK2 proteins are activated mainly
      by the haematopoietic growth factors. The JAK2 mutation is present in most
      patients with polycythaemia vera and about 50% of patients with essential
      thrombocytosis and idiopathic myelofibrosis. The identification of the JAK2
      mutation is a major molecular breakthrough in the understanding of the
      pathobiology of these disorders, and it is a new molecular marker to be used in
      the future classification of the diseases as well as a simple and rapid
      diagnostic test. The mutated JAK2 tyrosine kinase is an obvious potential target
      for a small-molecule inhibitor of tyrosine kinase activity.

PMID- 17032593
TI  - [Chronic inflammation increases the risk of cardiovascular disease in patients
      with rheumatoid arthritis].
AB  - Rheumatoid arthritis is associated with increased cardiovascular morbidity and
      mortality due to atherosclerosis. This cannot be explained by an increased
      presence of traditional risk factors but seems to depend on inflammatory
      mechanisms. The association of inflammatory pathways with atherosclerosis is
      complex, and more research is required to optimise preventative measures against
      cardiovascular complications in inflammatory rheumatic diseases.

PMID- 17032594
TI  - [Colorectal foreign bodies].
AB  - A patient with a retained anally introduced colorectal foreign body or
      complications hereof needs appropriate treatment. The patient may be in danger
      and is certainly in discomfort. The problem is relatively rare; however, its
      incidence may be expected to increase. Guidelines for handling of the situation
      are lacking in many textbooks. Here, a suggestion for handling of a patient with
      a retained colorectal foreign body or complications hereof is presented.

PMID- 17032595
TI  - [Selenium and health].
AB  - Selenium is an essential micronutrient. The average selenium intake in Danish
      adults is close to the recommended level of 40-50 mg/day. There is no scientific
      documentation showing that an increased selenium intake will result in disease
      prevention. However, a preventive effect on some cancers and hearth disease
      cannot be ruled out. Fortification of foods via increased selenium content in
      fertilizers is a possible way of increasing selenium intake. The tolerable upper
      intake level of 60 mg/day in children 1-3 years old must not be exceeded, which
      makes fortification difficult.

PMID- 17032596
TI  - [Tibialis posterior tendon dysfunction. An often neglected cause of painful adult
      flatfoot].
AB  - The posterior tibialis tendon is the most important dynamic stabilizer of the
      medial longitudinal arch of the foot. Posterior tibial tendon dysfunction (PTTD)
      may result from an acute trauma or a progressive degeneration of the tendon and
      should be suspected in painful flatfoot. The diagnosis is largely clinical, based
      on pain, tenderness and swelling along the tendon underneath the medial
      malleolus, the too-many-toes sign and persistant hindfoot valgus during heel
      rise. Untreated PTTD often results in total collapse of the longitudinal arch and
      severe osteoarthritis of the ankle or hindfoot. In traumatic cases acute repair
      of the tendon should be considered.

PMID- 17032597
TI  - [Alcohol consumption by middle-aged and elderly Danes from 1987 to 2003].
AB  - INTRODUCTION: The trend in alcohol consumption by middle-aged and elderly Danes
      has received little attention, but earlier studies indicated increased
      consumption. Social factors may influence the trend. Our objective was to
      investigate the trend in alcohol consumption by the middle-aged and elderly and
      inquire about significant trends among specific social subgroups. MATERIALS AND
      METHODS: In the Danish Health and Morbidity Survey carried out in 1987, 1994,
      2000 and 2003, a total of 11,754 people aged 50 and older were asked about their
      alcohol consumption. The mean alcohol intake and the number of heavy drinkers
      were compared from year to year. RESULTS: The mean intake per day increased from
      1.5 drinks in 1987 to 2.1 drinks in 2003 for men and from 0.5 drink in 1987 to
      1.0 drink in 2003 for women. The percentage of elderly drinking above the
      sensible drinking limits increased from 15.2% to 20.4% for men and from 10.7% to
      13.6% for women. The strongest increasing trend in the number of heavy drinkers
      was in the lowest socio-economic groups and among those married or cohabiting.
      CONCLUSION: The increased number of heavy drinkers among the middle-aged and
      elderly is of great importance to their general state of health. The increase has
      possibly been caused by a social and cultural development which has led to a
      generation of elderly who used to drink alcohol earlier in their lives and
      continue drinking in old age. More focus on alcohol consumption among the middle
      aged and elderly in health policy initiatives is needed.

PMID- 17032598
TI  - [Patients' satisfaction with the Mobile Emergency Care Unit in Copenhagen].
AB  - INTRODUCTION: Patients' satisfaction with physician-staffed ambulances in
      Copenhagen had not previously been investigated. We therefore conducted a survey
      of patients' satisfaction with the Mobile Emergency Care Unit (MECU) in
      Copenhagen. MATERIALS AND METHODS: The period of investigation was from 1
      September 2003 to 31 December 2003. Patients with a diagnosis of COPD, asthma or
      a cardiac disease were eligible for inclusion. Patients were excluded if they had
      not yet been discharged from hospital, were registered as deceased, were under
      the age of 18, were without a known address or had previously been included.
      RESULTS: During the period of investigation, 282 questionnaires were sent out;
      225 were returned, for a response rate of 80%. The patients' mean age was 71 (18
      99 years). On the part of 96% of the patients, the general impression of the MECU
      was very good or good, and 85% felt more confident when being treated by a
      physician in addition to the regular ambulance crew. The majority (80%) felt that
      the information given by the physician had been good, and 90% that the conduct of
      the physician had been satisfactory or better. In 11 questionnaires the patients,
      in their own words, described dissatisfaction with part of the MECU. In seven
      cases this concerned the conduct of or the information given by the ambulance
      crew. Most of the patients and physicians felt that the efforts of the MECU had
      improved the patient's condition. CONCLUSION: We conclude that in general
      patients are satisfied with the service provided by the MECU. They are aware of,
      and feel more confident when being treated by, a physician in addition to the
      regular ambulance crew. Reasons for dissatisfaction were the conduct of and the
      information given by the physician.

PMID- 17032599
TI  - [Fatal cases of poisoning in eastern Denmark during a five-year period (1998
      2002)].
AB  - INTRODUCTION: The goal of this investigation was to determine the pattern of
      fatal poisonings in eastern Denmark from 1998 to 2002 and compare it with similar
      investigations from 1979 to 1996. MATERIALS AND METHODS: The material included
      2,996 autopsies from eastern Denmark in which extensive forensic chemical
      investigations were performed. RESULTS: Of the 2,996 autopsies, 694 cases were
      drug addicts, in whom 497 fatal overdoses were detected, while in the remaining
      2,302 cases of nonaddicts, 443 fatal poisonings were determined. Morphine
      (heroine) and methadone were the main causes of death among the fatal poisonings
      of the drug addicts, accounting for 90% of the cases. The fatal poisonings among
      the nonaddicts were due mainly to medicine (73% of the cases); 13% were due to
      carbon monoxide and/or cyanide poisoning, and 12% were due to acute ethanol
      poisoning. The medicine was a wide range of strong and weak analgesics,
      antidepressants and antipsychotic drugs of older and newer origins. Comparison
      with earlier investigations from 1979 to 1996 showed that the poisoning pattern
      had changed, but similarities were also seen. The most frequently occurring drugs
      involved in fatal poisonings in eastern Denmark from 1979 to 2002 were morphine,
      methadone, ethanol and carbon monoxide/cyanide, of which methadone increased in
      occurrence over the 23-year period. CONCLUSION: The investigation of fatal
      poisonings is an important element in monitoring changes in drug abuse and
      poisoning patterns and levels.

PMID- 17032600
TI  - [Life-threatening liver failure and severe dyscrasias in blood and lymph nodes
      caused by sulphasalazine].
AB  - We report a case of sulphasalazine-related drug-induced hypersensitivity syndrome
      (the "three-week sulphasalazine syndrome") in which periferal T-cell lymphoma was
      a provisory diagnosis. A 40-year-old woman with seropositive rheumatoid arthritis
      was admitted to a local hospital 26 days after initiation of sulphasalazine
      treatment. She had fever, lymphadenopathy, dermatitis and facial oedema and
      showed biochemical signs of progressive hepatitis. Peripheral blood counts showed
      elevated leucocyte count with 15% atypical plasmacytes. Lymph node biopsy showed
      altered follicular architecture, a diffuse CD 4 positive predominance and
      histiocytes with erythrophagocytosis. Investigation by gene rearrangement for
      clonality of B- and T-lymphocytes ruled out the suspicion of lymphoma.
      Haematological and near-fatal hepatological changes resolved following
      discontinuation of sulphasalazine and a three-week course of glucocorticoid
      therapy. Early awareness of this syndrome via measuring liver function tests on,
      e.g., days 14-35 in patients started on sulphasalazine is recommended.

PMID- 17032602
TI  - [100 years with Alzheimer disease].

PMID- 17032603
TI  - [Lifestyle-related risk factors for dementia].
AB  - Emerging knowledge about modifiable risk factors for dementia has given rise to
      interventions that can potentially prevent or delay the onset of dementia and the
      possible target periods for intervention extend from prenatal period to old age.
      Factors during early life such as nutrition, education, and parental
      socioeconomic status can influence the development of dementia later in life.
      From mid to late life, a physically, socially, and intellectually active
      lifestyle is associated with reduced risk for dementia. Moreover, modification of
      cardiovascular risk factors during this period can potentially reduce risk for
      dementia.

PMID- 17032604
TI  - [Dementia--genetic aspects].
AB  - Several prevalent, sporadic neurodegenerative disorders also occur as rare
      inherited variants. Mapping of the genes involved in rare variants of the
      disorders has contributed to elucidating pathogenetic pathways for several
      dementia disorders, and the increased knowledge creates a possibility for
      development of new molecular genetic methods for diagnostics and for the
      treatment of the different types of dementia. Although inherited dementia
      disorders are generally rare, a genetic basis should always be considered when
      facing a patient with a recently clinically diagnosed dementia disorder.

PMID- 17032605
TI  - [Depression and the risk of Alzheimer's disease].
AB  - A population based cohort study consisting of 3346 participants aged 65-84 years
      was examined at baseline (1992-94) and after two and five years. The purpose was
      to examine whether a history of depression increased the risk of Alzheimer's
      disease (AD). History of depression was based on self-report and AD was diagnosed
      according to NINCDS-ADRDA. Logistic regression was used to calculate the odds
      ratio (OR (95% confidence interval)). Subjects with a history of depression had
      an increased risk of AD: Baseline (OR = 1,7 (1,0-2,7)); after two years (1,9 (1,0
      3,3)); after five years (1,6 (0,9-2,7)).

PMID- 17032606
TI  - [Screening and case finding instruments for depression--results from a Cochrane
      review].

PMID- 17032607
TI  - [Diagnostic imaging in dementia evaluation].
AB  - INTRODUCTION: The aim of the study was to evaluate the changes in diagnoses and
      treatment by structural scanning in dementia evaluation. MATERIAL AND METHODS:
      336 elderly, consecutively evaluated patients from two university memory clinics
      (mean age 75 y, mean MMSE 21.7), were retrospectively diagnosed without and with
      inclusion of scan results. These results were compared to prospective data
      obtained from 137 patients scanned as part of a population based study (The
      Odense Study, mean age 78.5, mean MMSE 23.3). CT and MRI were performed in 93%
      and 7% of the patients, respectively. RESULTS: Potentially reversible structural
      pathology was found in 3.5% of the memory clinic patients, and in 2% of the
      population based patients. By applying international diagnostic criteria and
      treatment recommendations to the retrospective memory clinic data, it was found
      that adding a structural scan changed diagnoses and treatment in 37% and 33% of
      the patients, primarily due to identification of cerebrovascular disease (CVD) in
      patients with no clinical signs or symptoms of CVD. In comparison, the change in
      diagnosis found in the prospective population data was lower (15%). It was not
      possible to identify a group of patients that would not benefit from scanning.
      CONCLUSION: Our data support recent guidelines that suggest CT scan as a routine
      investigation in dementia evaluation.

PMID- 17032608
TI  - [Memory problems among elderly patients in general practice: the importance of
      caregiver information].
AB  - INTRODUCTION: The aim was to describe and analyse signs that make caregivers
      suspect memory problems among elderly patients in general practice. METHODS: This
      prospective study was conducted in October and November 2002 among all patients
      aged 65 or older who consulted a GP in a total of 17 practices in Copenhagen
      inner city. The patients who agreed to participate were asked to complete a
      questionnaire regarding memory, quality of life, etc. Their GP completed a
      questionnaire independently, and a MMSE was subsequently given to the patient.
      Where consent was obtained from a patient, a postal questionnaire regarding the
      patient's memory was mailed to a caregiver chosen by the patient. RESULTS: Out of
      775 patients 62% (483) gave consent to contact a caregiver. Among the caregivers
      who received the questionnaire a total of 74% returned the questionnaire. A total
      of 88 (26%) of the caregivers suspected that the patient had memory problems.
      Predictors for caregiver suspicion of memory problems were: patient had
      complained about memory problems to caregiver (OR 21.7), caregiver had received
      information for other sources that the patient suffered from memory problems (OR
      5.0), a MMSE in the interval between 0-24 (OR 4.5) and a low quality of life (OR
      3.1). Furthermore, if the patient was male, caregivers were more likely to report
      memory problems. CONCLUSION: Memory impairment is commonly observed by
      caregivers, but is rarely discussed with a GP. The results indicate that more
      focus on the possibility of memory impairment among elderly patients is important
      in general practice.

PMID- 17032609
TI  - [Medical treatment of Alzheimer's disease].
AB  - In Denmark, Alzheimer drugs have been registered since 1997. Three cholinesterase
      inhibitors (donepezil, rivastigmin og galantamin) are approved mild to moderate
      Alzheimer's disease and one partial NMDA receptor antagonist (memantin) with the
      indication moderate to severe Alzheimer's disease. The treatment is symptomatic
      with a parallel shift of the course. The life expectancy does not seem to be
      altered. There is documented effect on the cholinesterase inhibitors of up to two
      years and for memantine for 6 months. New disease modifying agents are under
      clinical development.

PMID- 17032610
TI  - [Psychopharmacological treatment of behavioral and psychological symptoms in
      dementia].
AB  - Behavioural and psychological symptoms of dementia (BPSD) are common and can
      dominate disease presentation. Antidepressions are commonly prescribed for
      depressive symptoms, but the evidence to support this practice is weak. The
      atypical antipsychotics risperidone and olanzepine have significant efficacy for
      the treatment of aggression and risperidone is also efficacious in the treatment
      of psychosis, but both with substantially increased risk of stroke. There are no
      newer studies of benzodiazepines in the treatment of anxiety and in old studies
      the efficacy are doubtful.

PMID- 17032611
TI  - [The future economic burden of dementia on health and social services].
AB  - INTRODUCTION: Demographic changes in Denmark over the next 15 years will result
      in an increased number of elderly people and of individuals with dementia. As a
      result this will increase the demand for health care and social services. The aim
      of this study was to shed light on the likely economic consequences of this
      development. MATERIALS AND METHODS: A simple static, comparative model based on
      Danish incidence and cost data for different age groups and different levels of
      dementia severity was developed. The model projected the costs of the health and
      social services for treatment and care of people with dementia up to the year
      2020. RESULTS: The future demographic changes and an increasing number of people
      with dementia will result in a 30% increase in health and social service costs
      due to dementia. This increase will be lower if individuals with dementia have a
      higher mortality rate than other individuals. If annual productivity gains of 1
      3% can be achieved, the future cost (in real prices) could be reduced.
      CONCLUSION: The Danish health and social services will in the future be faced
      with increased costs for the treatment and care of people with dementia. This
      could be achieved through productivity gains, an increased level of financing or
      prioritisation of services that provide good value for money.

PMID- 17032612
TI  - [Communications in health care-- with a focus on adult patients' and
      children's/adolescents' perspectives of quality].
AB  - In this article communications problems in health care are illuminated from the
      perspectives of both adult patients and children. Factors that promote successful
      communication are described and studies about the effect of communication courses
      reviewed. Lack of information and responsiveness are among the problems most
      often reported. The perspective of children and adolescents is a relatively
      unexplored area. Studies investigating the effects of communication courses from
      patients' perspectives are required.

PMID- 17032613
TI  - [Sun and cancer].

PMID- 17032614
TI  - Genotypic variation of N2-fixing common bean (Phaseolus vulgaris L.) in response
      to iron deficiency.
AB  - In calcareous soils, the yield of grain legumes is often limited by the lower
      availability of iron (Fe), especially when they depend upon symbiosis with root
      nodule bacteria for their N nutrition. In order to explore the variability of
      responses of N(2)-fixing common bean to Fe deficiency the common bean white
      seeded lines Striker and Coco blanc, and coloured-seeded lines SVM-29-21 and
      ARA14 were inoculated with Rhizobium tropici (CIAT 899) and cultivated
      hydroaeroponically with a N-free nutrient solution supplied or not with 45microM
      Fe. Differences among lines were observed: Fe-deficiency-induced-chlorosis on
      young leaves was earlier and more severe in some lines than others. Nodule
      development and N(2)-fixing capacity was less affected in line ARA14 which
      preferentially allocated Fe towards nodules. Results suggest that Fe use
      efficiency for symbiotic nitrogen fixation (FeUE SNF) could be used to screen
      tolerant bean lines to Fe deficiency in condition of symbiotic nitrogen fixation.

PMID- 17032615
TI  - Reactive oxygen metabolism in mycorrhizal and non-mycorrhizal citrus (Poncirus
      trifoliata) seedlings subjected to water stress.
AB  - The effect of the arbuscular mycorrhizal (AM) fungus, Glomus versiforme, on
      growth and reactive oxygen metabolism of trifoliate orange (Poncirus trifoliata)
      seedlings was studied in potted plants under well-watered (WW) and water stressed
      (WS) conditions. Water stress significantly decreased root colonization. Shoot
      dry weight, plant height and stem diameter were higher in AM than in non-AM
      seedlings regardless of the water status. Inoculation with G. versiforme
      increased root dry weight and leaf number per plant of WW seedlings. There was
      less malondialdehyde (MDA) concentration in leaves and roots of AM seedlings, as
      well as lower hydrogen peroxide (H(2)O(2)) and superoxide anion radical (O(2)(-))
      concentrations in AM roots under WW and WS conditions. AM inoculation did not
      affect the H(2)O(2) and O(2)(-) concentrations of WW leaves. Whether WS or not,
      AM symbiosis notably increased the guaiacol peroxidase (G-POD) activity of
      leaves, glutathione reductase (GR) activity of leaves and ascorbate peroxidase
      (APX) activity of roots. AM infection also markedly increased the APX activity of
      WS leaves. Soluble proteins and glutathione (GSH) in leaves and roots and
      ascorbate (ASC) in leaves were higher in WW AM than in WW non-AM seedlings. AM
      infection also enhanced the ASC and GSH contents of leaves and roots in WS
      seedlings. Cross-tolerance might occur in AM plants and be enhanced by AM
      symbiosis. Our results suggest that the increased concentrations of antioxidant
      enzymes and non-enzymatic antioxidants found in AM plants may serve to protect
      the organism against oxidative damage, enhancing drought tolerance.

PMID- 17032616
TI  - Salicylic acid accumulates in the roots and hypocotyl after inoculation of
      cucumber leaves with Colletotrichum lagenarium.
AB  - Increased amounts of salicylic acid (SA) were detected in the roots and hypocotyl
      of cucumber plants (Cucumis sativus) using high-performance liquid chromatography
      following inoculation of the leaves with the anthracnose pathogen, Colletotrichum
      lagenarium. The concentrations of SA in the internodes immediately below the
      infected leaves increased to more than 1microg/g fresh weight. In contrast, the
      concentrations of SA in stems distant from, or above the infected leaves
      increased to 100-300ng/g. An increase in SA levels was observed in the upper stem
      2d after inoculation, followed by the hypocotyl with an increase detected 4d
      after inoculation. An initial increase in the SA levels was detected in the stem,
      followed by an increase in SA levels in the root from a basal level of
      approximately 300ng/g to more than 1microg/g. The increased level of SA in the
      lower leaves was less than 100ng/g. These results indicate that the levels of SA
      in the hypocotyl and root increased significantly following inoculation of the
      leaves with a microorganism capable of inducing SAR.

PMID- 17032617
TI  - The reactive oxygen species are involved in resistance responses of wheat to the
      Russian wheat aphid.
AB  - The effect of Russian wheat aphid (RWA), Diuraphis noxia (Mordvilko), infestation
      on the hydrogen peroxide (H(2)O(2)) content and NADPH oxidase (EC 1.6.3.1)
      activity was studied in the resistant (cv. Tugela DN) and near-isogenic
      susceptible (cv. Tugela) wheat (Triticum aestivum L.). The objective of this
      study was to investigate the involvement of the reactive oxygen species (ROS)
      during the resistance responses against the RWA. Infestation significantly
      induced an early accumulation of the H(2)O(2) and increase of NADPH oxidase
      activity to higher levels in the resistant than susceptible plants. Results of
      inhibitory studies using diphenylene iodonium (DPI), a suicide inhibitor of NADPH
      oxidase, strongly suggested a possible signalling role for H(2)O(2) during RWA
      resistance response by activation of downstream defence enzymes [intercellular
      peroxidase (EC 1.11.1.7) and beta-1,3-glucanase (EC 3.2.1.39)].

PMID- 17032618
TI  - Thidiazuron influences the endogenous levels of cytokinins and IAA during the
      flowering of isolated shoots of Dendrobium.
AB  - This study reports the effects of thidiazuron (TDZ) on the endogenous levels of
      indoleacetic acid (IAA), zeatin, zeatin riboside ([9R]Z), isopentenyladenine and
      isopentenyladenosine ([9R]iP) as well as structural changes in the apical
      meristem of Dendrobium Second Love shoots during flower induction and initial
      development in vitro. The results revealed that the presence of 1.8microM TDZ had
      a profound effect on the endogenous cytokinins (CKs) and IAA levels of the
      explants, when compared to those grown on a TDZ-free medium. A significant
      increase in CKs (especially [9R]iP and [9R]Z) and IAA in the first samples (taken
      at day 5) grown on TDZ-enriched medium was associated with flower induction,
      while a second increase in the level of these hormones after 25d of culture was
      related to flower development. The histological changes detected in the shoot
      apical meristem of explants grown in the presence of 1.8microM TDZ during 30d of
      culture are also described. Based on these findings, it is suggested that both
      auxin and CKs seem to be involved with the floral transition of Dendrobium Second
      Love in vitro. However, a possible direct effect of TDZ on flower formation is
      not discarded.

PMID- 17032619
TI  - Transgenic Arabidopsis plants expressing the rice dehydroascorbate reductase gene
      are resistant to salt stress.
AB  - Vitamin C (l-ascorbate) is important for antioxidative and metabolic functions in
      both plants and humans. Ascorbate itself is oxidized to dehydroascorbate during
      the process of antioxidation, and dehydroascorbate reductase (DHAR, EC 1.8.5.1)
      re-reduces the oxidized ascorbate. Therefore, this enzyme is assumed to be
      critical for ascorbate recycling. Here we show that the expression of rice DHAR
      in transgenic Arabidopsis thaliana enhanced resistance to salt stress. Salt
      tolerance was remarkably improved despite slight increases in DHAR activity and
      total ascorbate. This study provides direct evidence for the importance of DHAR
      in salt tolerance.

PMID- 17032620
TI  - Isolation of microprotoplasts from a partially synchronized suspension culture of
      Citrus unshiu.
AB  - The effect of hydroxyurea (HU) and amiprophos-methyl (APM) on the synchronization
      of suspension cultures of Satsuma mandarin (Citrus unshiu) and micronucleation of
      the suspension cells sequentially treated with both, HU and APM, were
      investigated. When suspension cultures in early-log phase were treated with 4 or
      10mM HU for 24h, the number of cells in the S-phase and the mitotic index (MI)
      increased significantly. Exposure of the early-log phase suspension culture to
      32microM APM led to a marked increase in the MI 12 and 24h after treatment, while
      higher as well as lower concentrations (16, 24 and 48microM) had no effect.
      Suspension cultures subjected to sequential treatment, e.g. pretreatment with
      10mM HU for 24h followed by treatment with 32microM APM for 24h, also showed a
      considerably increased MI. Furthermore, 61.5% of the protoplasts isolated from
      the sequentially treated suspension cells were micronucleated, whereas only 3.6%
      of the control protoplasts, isolated from untreated cells, showed
      micronucleation. Ultra-centrifugation of the micronucleated protoplasts generated
      microprotoplasts of different sizes, most of them below 5microM in diameter, with
      1 or few chromosomes. The potential application of microprotoplasts in citrus
      genetic improvement is discussed.

PMID- 17032621
TI  - Changes in content and fatty acid profiles of total lipids of two halophytes:
      Sesuvium portulacastrum and Mesembryanthemum crystallinum under cadmium stress.
AB  - Changes in lipid content and fatty acid composition were determined in leaves of
      two halophytes: Sesuvium portulacastrum and Mesembryanthemum crystallinum exposed
      to cadmium (Cd). Experiments were carried out using young small-sized plants
      grown hydroponically (S. portulacastrum) or aseptically germinated seeds (M.
      crystallinum). Cd treatment was applied at different concentrations (0, 50, 100
      and 200microM) for 30 days. At high cadmium doses (200microM), contents of total
      lipids (TL) and lipid fractions including galactolipids (GL), phospholipids (PL)
      and neutral lipids (NL) decreased more in M. crystallinum leaves than in S.
      portulacastrum leaves. Moreover, there were no significant changes in the total
      fatty acid composition of S. portulacastrum leaves during metal treatment. In
      contrast, M. crystallinum leaves showed a decrease in the percentage of the tri
      unsaturated fatty acid (C18:3), and a corresponding increase in the percentage of
      di-unsaturated fatty acid (C18:2). These different responses suggested that S.
      portulacastrum seems to be more feasible for phytoremediation.

PMID- 17032622
TI  - Proteins induced by cadmium in soybean cells.
AB  - The cadmium (Cd)-induced changes in protein pattern and identification of metal
      stimulated polypeptides were analyzed in soybean cell suspension culture. The
      cell cultures were treated with various concentrations of Cd(2+) (3-10microM) for
      24, 48 and 72h. The synthesis of [(35)S]-labeled proteins and their accumulation
      were analyzed by SDS-PAGE, whereas the identification of selected protein bands
      was performed by mass spectrometry. It is shown that Cd induced the appearance of
      the following proteins in soybean cells: superoxide dismutase, histone H2B,
      chalcone synthase and glutathione transferase.

PMID- 17032623
TI  - Research in shared decision making is growing deeper roots and more branches.

PMID- 17032625
TI  - Comparison of composition and antifungal activity of Artemisia argyi Levl. et
      Vant inflorescence essential oil extracted by hydrodistillation and supercritical
      carbon dioxide.
AB  - Essential oil of Artemisia argyi Levl. et Vant inflorescence was obtained by
      supercritical CO(2) extraction and hydrodistillation. The oil was analyzed by gas
      chromatography/mass spectrometry to characterize its components and was also
      tested for antifungal activity. A total of 61 compounds were identified in the
      hydrodistilled oil. The major components were 1,8-cineole (4.46%), borneol
      (3.58%), terpinol (10.18%), spathulenol (10.03%), caryophyllene oxide (6.51%),
      juniper camphor (8.74%), Camazulene (2.05%), and camphor (3.49%). By using
      supercritical CO(2) at 50 degrees C and 10 MPa, the concentrations of previous
      main components were lower than oil obtained by hydrodistillation, while
      miscellaneous compounds were higher. The essential oil extracted by these two
      methods exhibited antifungal activity against Botrytis cinerea and Alternaria
      alternate, two common storage pathogens of fruits and vegetables. The inhibition
      of B. cinerea and A. alternate were 93.3 and 84.7% for oil extracted by
      hydrodistillation when exposed to a concentration of 1,000 mg L(-1), while values
      of 70.8 and 60.5% were observed from oil extracted by supercritical CO(2).

PMID- 17032626
TI  - Vascular endothelial growth factor and nitric oxide serum levels in arterial
      hypertension.
AB  - Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial
      cells and an inducer of the angiogenic procedure. Endothelial nitric oxide (NO)
      is a potent vasodilator. Because both are implicated in vascular function, it is
      possible that they would be significantly affected in arterial hypertension. The
      aim of the study was the investigation of the levels of the two substances in
      blood serum and their potential relation in patients with untreated essential
      arterial hypertension compared to healthy individuals. VEGF levels were found
      129.1 +/- 135.9 pg/mL in a group of 28 untreated hypertensive patients vs. 209.0
      +/- 133.3 pg/mL in a group of 28 healthy individuals (p = 0.008). Nitrites and
      nitrates levels (as an indirect index of calculating NO levels) were also lower
      in hypertensive patients than in healthy individuals (19.8 +/- 9.7 micromol/L vs.
      29.6 +/- 15.9 micromol/L, p = 0.014). A positive correlation between NOx
      (nitrites and nitrates levels) and VEGF was found in healthy individuals (r =
      0.55, p = 0.003), but there was no correlation in hypertensive patients. The
      significant decrease of serum VEGF and NO in arterial hypertension and the
      existence of a correlation between the two substances in healthy subjects that
      did not exist in the hypertensive patients are findings that need evaluation.

PMID- 17032627
TI  - Marital decision-making and the timing of first birth in rural China before the
      1990s.
AB  - Using a sample of couples drawn from the three provinces of Guangdong, Shandong,
      and Shaanxi, we investigated whether couples' increasing freedom to choose whom
      to marry influenced the timing of first birth in rural China during the four
      decades before the 1990s. The shortening of first-birth intervals in the period
      is found to be associated with the shift from arranged to free-choice marriages.
      The association is attributed largely to increased intimacy and coital frequency
      after marriage together with postponement of age at first marriage.

PMID- 17032631
TI  - Effect of gamma radiation on cytokine expression and cytokine-receptor mediated
      STAT activation.
AB  - PURPOSE: The expression of cytokine mRNA and their related transcription factors
      was examined in order to assess the effects of gamma radiation on the immune
      function of murine splenocytes. MATERIALS AND METHODS: Splenocytes were collected
      from seven-week-old female Balb/c mice, and then irradiated at a dose of 5 Gy of
      60Co gamma-ray at a dose rate of 1.394 Gy/min. Total RNA was extracted from both
      irradiated and non-irradiated splenocytes at 1/2, 1, 3, 6, and 24 h and analysed
      by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mRNA
      level of interferon (IFN)-gamma, which is a Th1-type (T helper cell type 1)
      cytokine, was reduced after 3 h post-irradiation, whereas the interleukin (IL)-2
      mRNA in the naive splenocytes had no significant changes within the 24 h after
      irradiation. Moreover, IFN-gamma and IL-2 mRNA expression in concanavalin A (Con
      A, 2.5 mug/ml) activated-splenocytes was significantly reduced by gamma
      irradiation. On the other hand, the mRNA level of the Th2 type (T helper cell
      type 2) cytokines, such as IL-4, IL-5 and IL-10, was increased both in naive and
      activated splenocytes, and pro-inflammatory cytokines were also rapidly induced
      in response to irradiation in naive splenocytes. Interestingly, gamma irradiation
      had no effect on transforming growth factor (TGF)-beta mRNA expression. Moreover,
      the mRNA levels of the leucine zipper trqnscription factor c-Maf and GATA binding
      protein-3 (GATA-3), which regulate IL-4 and IL-5 transcription, were found to
      have been up-regulated. However, the mRNA coding for interferon regulatory factor
      (IRF)-1, which is involved in IFN-gamma production, was reduced 6 h post
      irradiation. The level of signal transducers and activators of transcription
      (Stat)-1 and Stat-4 phosphorylation, which are activated by IFN-gamma and IL-12,
      respectively, was significantly reduced by gamma irradiation, but IL-4 receptor
      mediated Stat-6 activation remained unchanged. CONCLUSIONS: These results suggest
      that gamma irradiation may play a role in Th1 and Th2 cytokine expression, via
      regulation of the level of cytokine-mediators through transcriptional modulation
      and Stat signaling. These results are helpful to understand general profile of
      cytokine expression in response to gamma irradiation.

PMID- 17032632
TI  - Responding rapidly to FDA drug withdrawals: design and application of a new
      approach for a consumer health website.
AB  - BACKGROUND: Information about drug withdrawals may not reach patients in a timely
      manner, and this could result in adverse events. Increasingly, the public turns
      to consumer health websites for health information, but such sites may not update
      their content for days or weeks following important events like Food and Drug
      Administration (FDA) drug withdrawal actions. There is no recognized standard for
      how quickly consumer health websites should respond to such events, and reports
      addressing this issue are lacking. OBJECTIVE: The objective of this study was to
      develop and implement an approach to enhance the efficiency with which a consumer
      health website (NetWellness.org) responds to FDA drug withdrawal actions.
      METHODS: Evaluation of the current approach used by NetWellness staff to update
      content affected by FDA action revealed a slow process driven by the goal of
      performing thorough and comprehensive review and editing. To achieve our desired
      goal of accurately updating affected content within 24 hours of FDA action, we
      developed a strategy that included rapid updating of affected Web pages with
      warning boxes and hyperlinks to the information about the withdrawal. With the
      next FDA withdrawal event, that of valdecoxib (Bextra) on April 7, 2005, we
      applied this new approach, observed the time and resource requirements, and
      monitored the rate at which consumers viewed the updated information to gauge its
      potential impact. RESULTS: Application of the new approach allowed one person to
      modify the affected Web pages in less than 1 hour and within 18 hours of the FDA
      announcement. Using the old strategy, response to a similar event, the withdrawal
      of rofecoxib (Vioxx) 6 months earlier, had taken over 3 weeks and the efforts of
      several personnel. Updated valdecoxib content received 188 hits within the first
      month and 4285 hits within 1 year. CONCLUSIONS: Rapid updating of a consumer
      health website's content in response to an FDA drug withdrawal event was easily
      accomplished by applying the approach described. This allowed consumers to view
      accurate information regarding the withdrawn drug much sooner than would
      otherwise have been the case. Given that consumers increasingly turn to websites
      for their health information, adoption of a rapid response standard for important
      health events like FDA drug withdrawals should be considered by the consumer
      health informatics community.

PMID- 17032633
TI  - Characterizing Internet searchers of smoking cessation information.
AB  - BACKGROUND: The Internet is a viable channel to deliver evidence-based smoking
      cessation treatment that has the potential to make a large population impact on
      reducing smoking prevalence. There is high demand for smoking cessation
      information and support on the Internet. Approximately 7% (10.2 million) of adult
      American Internet users have searched for information on quitting smoking. Little
      is known about these individuals, their smoking status, what type of cessation
      services they are seeking on the Internet, or how frequently these searches for
      cessation information are conducted. OBJECTIVE: The primary goal of this study
      was to characterize individuals who search for smoking cessation information on
      the Internet to determine appropriate triage and treatment strategies. The
      secondary goal was to estimate the incidence of searches for cessation
      information using publicly available search engine data. METHODS: We recruited
      individuals who clicked on a link to a leading smoking cessation website
      (QuitNet) from within the results of a search engine query. Individuals were
      "intercepted" before seeing the QuitNet home page and were invited to participate
      in the study. Those accepting the invitation were routed to an online survey
      about demographics, smoking characteristics, preferences for specific cessation
      services, and Internet search patterns. To determine the generalizability of our
      sample, national datasets on search engine usage patterns, market share, and
      keyword rankings were examined. These datasets were then used to estimate the
      number of queries for smoking cessation information each year. RESULTS: During
      the 10-day study period, 2265 individuals were recruited and 29% (N = 655)
      responded. Of these, 59% were female and overall tended to be younger than the
      previously characterized general Internet population. Most (76%) respondents were
      current smokers; 17% had quit within the last 7 days, and 7% had quit more than 7
      days ago. Slightly more than half of active smokers (53%) indicated that they
      were planning to quit in the next 30 days. Smokers were more likely to seek
      information on how to quit and on medications; former smokers were more
      interested in how to cope with withdrawal. All participants rated withdrawal
      information and individually tailored information as being more useful, while
      displaying little interest in telephone counseling, expert support, or peer
      support. Publicly available data from large search engines suggest that 4 million
      Americans search for resources on smoking cessation each year. CONCLUSIONS: This
      study adds to the limited data available on individuals who search for smoking
      cessation information on the Internet, supports the prior estimates of the size
      of the population, and indicates that these individuals are in appropriate stages
      for both active cessation interventions and aggressive relapse prevention
      efforts. Continued development and evaluation of online interventions is
      warranted, and organizations seeking to promote cessation should carefully
      evaluate the Internet as a possible modality for treatment and as a gateway to
      other traditional programs.

PMID- 17032634
TI  - Internet interventions or patient education web sites?

PMID- 17032636
TI  - The law of attrition revisited.

PMID- 17032638
TI  - Are physicians ready for patients with Internet-based health information?
AB  - BACKGROUND: An increasing number of patients bring Internet-based health
      information to medical consultations. However, little is known about how
      physicians experience, manage, and view these patients. OBJECTIVE: This study
      aimed to advance the understanding of the effects of incorporating Internet-based
      health information into routine medical consultations from physicians'
      perspectives, using a qualitative approach. METHODS: Six focus groups were
      conducted with 48 family physicians practising in Toronto. The data were analyzed
      using qualitative methods of content analysis and constant comparison, derived
      from grounded theory approach. RESULTS: Three overarching themes were identified:
      (1) perceived reactions of patients, (2) physician burden, and (3) physician
      interpretation and contextualization of information. Physicians in our study
      generally perceived Internet-based health information as problematic when
      introduced by patients during medical consultations. They believed that Internet
      information often generated patient misinformation, leading to confusion,
      distress, or an inclination towards detrimental self-diagnosis and/or self
      treatment. Physicians felt these influences added a new interpretive role to
      their clinical responsibilities. Although most of the physicians felt obliged to
      carry out this new responsibility, the additional role was often unwelcome.
      Despite identifying various reactions of patients to Internet-based health
      information, physicians in our study were unprepared to handle these patients.
      CONCLUSION: Effective initiatives at the level of the health care system are
      needed. The potential of Internet-based health information to lead to better
      physician-patient communication and patient outcomes could be facilitated by
      promoting physician acknowledgment of increasing use of the Internet among
      patients and by developing patient management guidelines and incentives for
      physicians.

PMID- 17032639
TI  - Directions for the International Society for Research on Internet Interventions
      (ISRII).
AB  - In 2004, the International Society for Research on Internet Interventions (ISRII)
      was formed to encourage eHealth researchers to collaborate in their efforts to
      further the science behind developing, testing, and disseminating Web-based
      treatment programs. The group held its second meeting (April 2006) to clarify the
      Society's direction and identify key issues that need addressing in the field.
      These issues are identified and examined in the current paper. Given the success
      of using the Internet to treat a range of medical and mental health problems, and
      the growing need for better dissemination of health care, Internet interventions
      will almost certainly play a prominent role in global health. ISRII plans to
      provide the necessary venue to ensure the science driving this field is strong,
      enabling researchers to conduct the highest quality research and permitting
      meaningful conclusions from completed studies.

PMID- 17032640
TI  - Is e-health progressing faster than e-health researchers?
AB  - Formal Internet interventions exist in a broad context of diverse online health
      resources, which share elements in common like information, advice and peer
      support. However, most online health resources are not created by healthcare
      professionals. Internet interventions need to be designed to "compete" in that
      wider context. The democratization of production and distribution is central to
      the transformative effect of the Internet on society, yet potentially conflicts
      with healthcare's need for an evidence base and safe practice. This is a core
      challenge for healthcare on the Internet.

PMID- 17032641
TI  - Global roles of Ste11p, cell type, and pheromone in the control of gene
      expression during early sexual differentiation in fission yeast.
AB  - Fission yeast cells belong to one of two specialized cell types, M or P. Specific
      environmental conditions trigger sexual differentiation, which leads to an
      internal program starting with pheromone signaling between M and P cells,
      followed by mating, meiosis, and sporulation. The initial steps of this process
      are controlled by Ste11p, a master transcriptional regulator that activates the
      expression of cell type-specific genes (only expressed in either M or P cells) as
      well as genes expressed in both M and P cells. Pheromone signaling is activated
      by Ste11p-dependent transcription and, in turn, enhances some of this
      transcription in a positive feedback. To obtain a genomewide view of Ste11p
      target genes, their cell-type specificity, and their dependence on pheromone, we
      used DNA microarrays along with different genetic and environmental manipulations
      of fission yeast cells. We identified 78 Ste11p-dependent genes, 12 and 4 of
      which are only expressed in M and P cells, respectively. These genes show
      differing grades of pheromone dependencies for Ste11p-activated transcription,
      ranging from complete independence to complete dependence on pheromone. We
      systematically deleted all novel cell type-specific genes and characterized their
      phenotype during sexual differentiation. A comparison with a similar data set
      from the distantly related budding yeast reveals striking conservation in both
      number and types of the proteins that define cell types. Given the divergent
      mechanisms regulating cell type-specific gene expression, our results highlight
      the plasticity of regulatory circuits, which evolve to allow adaptation to
      changing environments and lifestyles.

PMID- 17032642
TI  - Enhanced amyloidogenic metabolism of the amyloid beta-protein precursor in the
      X11L-deficient mouse brain.
AB  - X11L, a neuronal adaptor protein, associates with the cytoplasmic domain of APP
      and suppresses APP cellular metabolism. APP is the precursor of Abeta, whose
      metabolism is strongly implicated in Alzheimer disease pathogenesis. To examine
      the roles of X11L function in APP metabolism, including the generation of Abeta
      in the brain, we produced X11L-deficient mutant mice on the C57BL/6 background.
      The mutant mice did not exhibit histopathological alterations or compensatory
      changes in the expression of other X11 family proteins, X11 and X11L2. The
      expression level and distribution of APP in the brain of mutant mice were also
      identical to those in wild-type mice. However, in the hippocampus, where
      substantial levels of X11L and APP are expressed, the mutant mice exhibited a
      significant increase in the level of the C-terminal fragments of APP produced by
      cleavage with beta-secretase but not alpha-secretase. The levels of Abeta were
      increased in the hippocampus of aged mutant mice as compared with age-matched
      controls. These observations clearly indicate that X11L suppresses the
      amyloidogenic but not amyloidolytic processing of APP in regions of the brain
      such as the hippocampus, which express significant levels of X11L.

PMID- 17032643
TI  - Regulation of catalysis by the smallpox virus topoisomerase.
AB  - The poxvirus type IB topoisomerases catalyze relaxation of supercoiled DNA by
      cleaving and rejoining DNA strands via a pathway involving a covalent
      phosphotyrosine intermediate. Recently we determined structures of the smallpox
      virus topoisomerase bound to DNA in covalent and non-covalent DNA complexes using
      x-ray crystallography. Here we analyzed the effects of twenty-two amino acid
      substitutions on the topoisomerase activity in vitro in assays of DNA relaxation,
      single cycle cleavage, and equilibrium cleavage-religation. Alanine substitutions
      at 14 positions impaired topoisomerase function, marking a channel of
      functionally important contacts along the protein-DNA interface. Unexpectedly,
      alanine substitutions at two positions (D168A and E124A) accelerated the forward
      rate of cleavage. These findings and further analysis indicate that Asp(168) is a
      key regulator of the active site that maintains an optimal balance among the DNA
      cleavage, religation, and product release steps. Finally, we report that high
      level expression of the D168A topoisomerase in Escherichia coli, but not other
      alanine-substituted enzymes, prevented cell growth. These findings help elucidate
      the amino acid side chains involved in DNA binding and catalysis and provide
      guidance for designing topoisomerase poisons for use as smallpox antivirals.

PMID- 17032644
TI  - Biochemical and genetic analysis of methylenetetrahydrofolate reductase in
      Leishmania metabolism and virulence.
AB  - Methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) is the sole enzyme
      responsible for generation of 5-methyltetrahydrofolate, which is required for
      methionine synthesis and provision of methyl groups via S-adenosylmethionine.
      Genome analysis showed that Leishmania species, unlike Trypanosoma brucei and
      Trypanosoma cruzi, contain genes encoding MTHFR and two distinct methionine
      synthases. Leishmania MTHFR differed from those in other eukaryotes by the
      absence of a C-terminal regulatory domain. L. major MTHFR was expressed in yeast
      and recombinant enzyme was produced in Escherichia coli. MTHFR was not inhibited
      by S-adenosylmethionine and, uniquely among folate-metabolizing enzymes, showed
      dual-cofactor specificity with NADH and NADPH under physiological conditions.
      MTHFR null mutants (mthfr(-)) lacked 5-methyltetrahydrofolate, the most abundant
      intracellular folate, and could not utilize exogenous homocysteine for growth.
      Under conditions of methionine limitation mthfr(-) mutant cells grew poorly,
      whereas their growth was normal in standard culture media. Neither in vitro MTHFR
      activity nor the growth of mthfr(-) mutants or MTHFR overexpressors were
      differentially affected by antifolates known to inhibit parasite growth via
      targets beyond dihydrofolate reductase and pteridine reductase 1. In a mouse
      model of infection mthfr(-) mutants showed good infectivity and virulence,
      indicating that sufficient methionine is available within the parasitophorous
      vacuole to meet the needs of the parasite.

PMID- 17032645
TI  - Pre-steady state electrogenic events of Ca2+/H+ exchange and transport by the
      Ca2+-ATPase.
AB  - Native or recombinant SERCA (sarco(endo)plasmic reticulum Ca(2+) ATPase) was
      adsorbed on a solid supported membrane and then activated with Ca(2+) and ATP
      concentration jumps through rapid solution exchange. The resulting electrogenic
      events were recorded as electrical currents flowing along the external circuit.
      Current transients were observed following Ca(2+) jumps in the absence of ATP and
      following ATP jumps in the presence of Ca(2+). The related charge movements are
      attributed to Ca(2+) reaching its binding sites in the ground state of the enzyme
      (E(1)) and to its vectorial release from the enzyme phosphorylated by ATP
      (E(2)P). The Ca(2+) concentration and pH dependence as well as the time frames of
      the observed current transients are consistent with equilibrium and pre-steady
      state biochemical measurements of sequential steps within a single enzymatic
      cycle. Numerical integration of the current transients recorded at various pH
      values reveal partial charge compensation by H(+) in exchange for Ca(2+) at
      acidic (but not at alkaline) pH. Most interestingly, charge movements induced by
      Ca(2+) and ATP vary over different pH ranges, as the protonation probability of
      residues involved in Ca(2+)/H(+) exchange is lower in the E(1) than in the E(2)P
      state. Our single cycle measurements demonstrate that this difference contributes
      directly to the reduction of Ca(2+) affinity produced by ATP utilization and
      results in the countertransport of two Ca(2+) and two H(+) within each ATPase
      cycle at pH 7.0. The effects of site-directed mutations indicate that Glu-771 and
      Asp-800, within the Ca(2+) binding domain, are involved in the observed
      Ca(2+)/H(+) exchange.

PMID- 17032646
TI  - Identification and characterization of abeta1,3-glucosyltransferase that
      synthesizes the Glc-beta1,3-Fuc disaccharide on thrombospondin type 1 repeats.
AB  - Thrombospondin type 1 repeats (TSRs) are biologically important domains of
      extracellular proteins. They are modified with a unique Glcbeta1,3Fucalpha1-O
      linked disaccharide on either serine or threonine residues. Here we identify the
      putative glycosyltransferase, B3GTL, as the beta1,3-glucosyltransferase involved
      in the biosynthesis of this disaccharide. This enzyme is conserved from
      Caenorhabditis elegans to man and shares 28% sequence identity with Fringe, the
      beta1,3-N-acetylglucosaminyltransferase that modifies O-linked fucosyl residues
      in proteins containing epidermal growth factor-like domains, such as Notch.
      beta1,3-Glucosyltransferase glucosylates properly folded TSR-fucose but not
      fucosylated epidermal growth factor-like domain or the non-fucosylated modules.
      Specifically, the glucose is added in a beta1,3-linkage to the fucose in TSR. The
      activity profiles of beta1,3-glucosyltransferase and protein O-fucosyltransferase
      2, the enzyme that carries out the first step in TSR O-fucosylation, superimpose
      in endoplasmic reticulum subfractions obtained by density gradient
      centrifugation. Both enzymes are soluble proteins that efficiently modify
      properly folded TSR modules. The identification of the beta1,3
      glucosyltransferase gene allows us to manipulate the formation of the rare
      Glcbeta1,3Fucalpha1 structure to investigate its biological function.

PMID- 17032647
TI  - Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal
      growth factor receptor-dependent ERK1/2 activation.
AB  - Catecholamine-stimulated lipolysis is primarily a beta-adrenergic and cAMP
      dependent event. In previous studies we established that the beta(3)-adrenergic
      receptor (beta(3)AR) in adipocytes utilizes a unique mechanism to stimulate
      extracellular signal-regulated kinases 1 and 2 (ERK) by direct recruitment and
      activation of Src kinase. Therefore, we investigated the role of the ERK pathway
      in adipocyte metabolism and found that the beta(3)AR agonist CL316,243 regulates
      lipolysis through both cAMP-dependent protein kinase (PKA) and ERK. Inhibition of
      PKA activity completely eliminated lipolysis at low (subnanomolar) CL316,243
      concentrations and by 75-80% at higher nanomolar concentrations. The remaining 20
      25% of PKA-independent lipolysis, as well as ERK activation, was abolished by
      inhibiting the activity of either Src (PP2 or small interfering RNA), epidermal
      growth factor receptor (EGFR with AG1478 or small interfering RNA), or mitogen
      activated protein kinase kinase 1 or 2 (MKK1/2 with PD098059). PD098059 inhibited
      lipolysis by 53% in mice as well. Finally, the effect of estradiol, a reported
      acute activator of ERK and lipolysis, was also totally prevented by PP2, AG1478,
      and PD098059. These results suggest that ERK activation by beta(3)AR depends upon
      Src and epidermal growth factor receptor kinase activities and is responsible for
      the PKA-independent portion of the lipolytic response. Together these results
      illustrate the distinct and complementary roles for PKA and ERK in catecholamine
      stimulated lipolysis.

PMID- 17032648
TI  - Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux.
AB  - To identify genes involved in the regulation of plasma high density lipoprotein
      (HDL) cholesterol (HDL-C) levels, patients with low HDL-C and age- and sex
      matched controls (normal HDL-C) were extensively characterized. Comparative
      transcriptome analysis was carried out in cholesterol-loaded monocyte-derived
      macrophages from low HDL subjects segregated into groups with or without
      cholesterol efflux defects or ABCA1 mutations. Clusters of differentially
      regulated genes were evident in the low HDL groups as compared with controls. Of
      particular note, expression of cathepsin D (CTSD), a lysosomal proteinase, was
      reduced by approximately 50% in monocyte-derived macrophages of low HDL-C
      subjects, most significantly those with cholesterol efflux defects but without
      mutations in ABCA1 (p < 0.01). These results were verified by reverse
      transcription-PCR and replicated in a second cohort. We show here that blocking
      the activity or expression of CTSD, by pepstatin or CTSD small interfering RNA,
      respectively, reduced ABCA1 expression and protein abundance in both macrophages
      and CHO cells and apolipoprotein A-I-mediated lipid efflux by more than 70%.
      Conversely, expression of CTSD increased both ABCA1 mRNA expression and cellular
      ABCA1 protein. Consistent with its role in the proteolytic processing of
      prosaposin, inactivation of CTSD function resulted in the accumulation of
      glycosphingo-lipid and free cholesterol in late endosomes/lysosomes, a phenotype
      similar to NPC1 deficiency. Inhibition of CTSD also caused retention of ABCA1 in
      lysosomal compartments, reducing its trafficking to the plasma membrane. These
      studies demonstrate a novel and potentially important role for CTSD in
      intracellular cholesterol trafficking and ABCA1-mediated efflux. Therefore,
      decreased CTSD expression may contribute to low plasma HDL-C levels.

PMID- 17032649
TI  - Rac1 GTPase regulates cell genomic stability and senescence.
AB  - The Rho family small GTPase Rac1 has been shown to play multiple roles in cell
      regulation, including actin cytoskeleton organization, transcriptional
      activation, microtubule dynamics, and endocytosis. Here, we report a novel role
      of Rac1 in regulating genomic stability and cell senescence. We observed in
      primary mouse embryonic fibroblasts that deletion of rac1 by gene targeting, as
      well as expression of the constitutively active Rac1 mutant L61Rac1, led to
      decreased cell growth that was associated with altered cell cycle progression at
      both G(1)/S and G(2)/M phases, increased apoptosis, and premature senescence. The
      senescence induction by either loss or gain of Rac1 activity was due at least in
      part to an increase in cellular reactive oxygen species (ROS). rac1 gene deletion
      caused a compensatory up-regulation of a closely related family member, Rac3, in
      mouse embryonic fibroblasts, the activity of which induced ROS production
      independently of Rac1. Furthermore, the Rac1-regulated ROS production and
      senescence correlated with the extent of DNA damage in the Rac1(-/-) and L61Rac1
      cells. Treatment of these cells with a ROS inhibitor inhibited phospho-H2AX
      positive nuclear focus formation. Finally, phospho-Ser(15) p53 was significantly
      increased in L61Rac1 and Rac1(-/-) cells, and genetic deletion of p53 from these
      cells readily reversed the senescence phenotype, indicating that Rac1 is
      functionally dependent on p53 in regulating cell senescence. Taken together, our
      results show that Rac1 activity serves as a regulator of cell senescence through
      modulation of cellular ROS, genomic stability, and p53 activity.

PMID- 17032650
TI  - Secretory granule biogenesis in sympathoadrenal cells: identification of a
      granulogenic determinant in the secretory prohormone chromogranin A.
AB  - Chromogranin A (CgA) may be critical for secretory granule biogenesis in
      sympathoadrenal cells. We found that silencing the expression of CgA reduced the
      number of secretory granules in normal sympathoadrenal cells (PC12), and we
      therefore questioned whether a discrete domain of CgA might promote the formation
      of a regulated secretory pathway in variant sympathoadrenal cells (A35C) devoid
      of such a phenotype. The secretory granule-forming activity of a series of human
      CgA domains labeled with a hemagglutinin epitope, green fluorescent protein, or
      embryonic alkaline phosphatase was assessed in A35C cells by deconvolution and
      electron microscopy and by secretagogue-stimulated release assays. Expression of
      CgA in A35C cells induced the formation of vesicular organelles throughout the
      cytoplasm, whereas two constitutive secretory pathway markers accumulated in the
      Golgi complex. The lysosome-associated membrane protein LGP110 did not co
      localize with CgA, consistent with non-lysosomal targeting of the granin in A35C
      cells. Thus, CgA-expressing A35C cells showed electron-dense granules
      approximately 180-220 nm in diameter, and secretagogue-stimulated exocytosis of
      CgA from A35C cells suggested that expression of the granin may be sufficient to
      restore a regulated secretory pathway and thereby rescue the sorting of other
      secretory proteins. We show that the formation of vesicular structures destined
      for regulated exocytosis may be mediated by a determinant located within the CgA
      N-terminal region (CgA-(1-115), with a necessary contribution of CgA-(40-115)),
      but not the C-terminal region (CgA-(233-439)) of the protein. We propose that CgA
      promotes the biogenesis of secretory granules by a mechanism involving a
      granulogenic determinant located within CgA-(40-115) of the mature protein.

PMID- 17032651
TI  - Negative constraints underlie the ErbB specificity of epidermal growth factor
      like ligands.
AB  - Epidermal growth factor (EGF)-like growth factors bind their ErbB receptors in a
      highly selective manner, but the molecular basis for this specificity is poorly
      understood. We have previously shown that certain residues in human EGF (Ser(2)
      Asp(3)) and TGFalpha (Glu(26)) are not essential for their binding to ErbB1 but
      prevent binding to ErbB3 and ErbB4. In the present study, we have used a phage
      display approach to affinity-optimize the C-terminal linear region of EGF-like
      growth factors for binding to each ErbB receptor and thereby shown that Arg(45)
      in EGF impairs binding to both ErbB3 and ErbB4. By omitting all these so-called
      negative constraints from EGF, we designed a ligand designated panerbin that
      binds ErbB1, ErbB3, and ErbB4 with similarly high affinity as their wild-type
      ligands. Homology models, based on the known crystal structure of TGFalpha-bound
      ErbB1, showed that panerbin is able to bind ErbB1, ErbB3, and ErbB4 in a highly
      similar manner with respect to position and number of interaction sites. Upon in
      silico introduction of the experimentally known negative constraints into
      panerbin, we found that Arg(45) induced local charge repulsion and Glu(26)
      induced steric hindrance in a receptor-specific manner, whereas Ser(2)-Asp(3)
      impaired binding due to a disordered conformation. Furthermore, radiolabeled
      panerbin was used to quantify the level of all three receptors on human breast
      cancer cells in a single radioreceptor assay. It is concluded that the ErbB
      specificity of EGF-like growth factors primarily results from the presence of a
      limited number of residues that impair the unintended interaction with other ErbB
      receptors.

PMID- 17032652
TI  - Identification of a lipase-linked cell membrane receptor for pigment epithelium
      derived factor.
AB  - Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional
      protein belonging to the serpin superfamily with demonstrable neurotrophic,
      gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We
      have previously provided biochemical evidence for high affinity PEDF-binding
      sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells.
      This study was designed to reveal a receptor involved in the biological
      activities of PEDF. Using a yeast two-hybrid screening, we identified a novel
      gene from pigment epithelium of the human retina that codes for a PEDF-binding
      partner, which we term PEDF-R. The derived polypeptide has putative
      transmembrane, intracellular and extracellular regions, and a phospholipase
      domain. Recently, PEDF-R (TTS-2.2/independent phospholipase A(2) (PLA(2))zeta and
      mouse desnutrin/ATGL) has been described in adipose cells as a member of the new
      calcium-independent PLA(2)/nutrin/patatin-like phospholipase domain-containing 2
      (PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase
      activities. Here we describe the PEDF-R gene expression in the retina and its
      heterologous expression by bacterial and eukaryotic systems, and we demonstrate
      that its protein product has specific and high binding affinity for PEDF, has a
      potent phospholipase A(2) activity that liberates fatty acids, and is associated
      with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the
      enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have
      identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane
      protein with high affinity for PEDF, suggesting a molecular pathway by which
      ligand/receptor interaction on the cell surface could generate a cellular signal.

PMID- 17032653
TI  - Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced
      degeneration in mice.
AB  - RDH12 has been suggested to be one of the retinol dehydrogenases (RDH) involved
      in the vitamin A recycling system (visual cycle) in the eye. Loss of function
      mutations in the RDH12 gene were recently reported to be associated with
      autosomal recessive childhood-onset severe retinal dystrophy. Here we show that
      RDH12 localizes to the photoreceptor inner segments and that deletion of this
      gene in mice slows the kinetics of all-trans-retinal reduction, delaying dark
      adaptation. However, accelerated 11-cis-retinal production and increased
      susceptibility to light-induced photoreceptor apoptosis were also observed in
      Rdh12(-/-) mice, suggesting that RDH12 plays a unique, nonredundant role in the
      photoreceptor inner segments to regulate the flow of retinoids in the eye. Thus,
      severe visual impairments of individuals with null mutations in RDH12 may likely
      be caused by light damage(1).

PMID- 17032654
TI  - Discovery of a new prokaryotic type I GTP cyclohydrolase family.
AB  - GTP cyclohydrolase I (GCYH-I) is the first enzyme of the de novo tetrahydrofolate
      biosynthetic pathway present in bacteria, fungi, and plants, and encoded in
      Escherichia coli by the folE gene. It is also the first enzyme of the biopterin
      (BH4) pathway in Homo sapiens, where it is encoded by a homologous folE gene. A
      homology-based search of GCYH-I orthologs in all sequenced bacteria revealed a
      group of microbes, including several clinically important pathogens, that encoded
      all of the enzymes of the tetrahydrofolate biosynthesis pathway but GCYH-I,
      suggesting that an alternate family was present in these organisms. A prediction
      based on phylogenetic occurrence and physical clustering identified the COG1469
      family as a potential candidate for this missing enzyme family. The GCYH-I
      activity of COG1469 family proteins from a variety of sources (Thermotoga
      maritima, Bacillus subtilis, Acinetobacter baylyi, and Neisseria gonorrhoeae) was
      experimentally verified in vivo and/or in vitro. Although there is no detectable
      sequence homology with the canonical GCYH-I, protein fold recognition based on
      sequence profiles, secondary structure, and solvation potential information
      suggests that, like GCYH-I proteins, COG1469 proteins are members of the tunnel
      fold (T-fold) structural superfamily. This new GCYH-I family is found in
      approximately 20% of sequenced bacteria and is prevalent in Archaea, but the
      family is to this date absent in Eukarya.

PMID- 17032655
TI  - Activation of platelet alphaIIbbeta3 by an exogenous peptide corresponding to the
      transmembrane domain of alphaIIb.
AB  - A transmembrane domain heterodimer, acting in concert with a membrane-proximal
      cytoplasmic domain clasp, is thought to maintain integrins in a low affinity
      state. To test whether helix-helix interactions between the alphaIIb and beta3
      transmembrane domains regulate the activity of integrin alphaIIbbeta3, we
      synthesized a soluble peptide corresponding to the alphaIIb transmembrane domain,
      designated alphaIIb-TM, and we studied its ability to affect alphaIIbbeta3
      activity in human platelets. alphaIIb-TM was alpha-helical in detergent micelles
      and phospholipid vesicles, readily inserted into membrane bilayers, bound to
      intact purified alphaIIbbeta3, and specifically associated with the transmembrane
      domain of alphaIIb, rather than the transmembrane domains of beta3, alpha2, and
      beta1, other integrin subunits present in platelets. When added to suspensions of
      gel-filtered platelets, alphaIIb-TM rapidly induced platelet aggregation that was
      not inhibited by preincubating platelets with the prostaglandin E(1) or the ADP
      scavenger apyrase but was prevented by the divalent cation chelator EDTA.
      Furthermore, alphaIIb-TM induced fibrinogen binding to platelets but not the
      binding of osteopontin, a specific ligand for platelet alphavbeta3. The peptide
      also induced fibrinogen binding to recombinant alphaIIbbeta3 expressed by Chinese
      hamster ovary cells, confirming that its effect was independent of platelet
      signal transduction. Finally, transmission electron microscopy of purified
      alphaIIbbeta3 revealed that alphaIIb-TM shifted the integrin from a closed
      configuration with its stalks touching to an open configuration with separated
      stalks. These observations demonstrate that transmembrane domain interactions
      regulate integrin function in situ and that it is possible to target intra
      membranous protein-protein interactions in a way that can have functional
      consequences.

PMID- 17032656
TI  - Evidence for the formation of a heptameric ion channel complex by the hepatitis C
      virus p7 protein in vitro.
AB  - The p7 protein of hepatitis C virus functions as an ion channel both in vitro and
      in cell-based assays and is inhibited by amantadine, long alkyl chain imino-sugar
      derivatives, and amiloride compounds. Future drug design will be greatly aided by
      information on the stoichiometry and high resolution structure of p7 ion channel
      complexes. Here, we have refined a bacterial expression system for p7 based on a
      glutathione S-transferase fusion methodology that circumvents the inherent
      problems of hydrophobic protein purification and the limitations of chemical
      synthesis. Rotational averaging and harmonic analysis of transmission electron
      micrographs of glutathione S-transferase-FLAG-p7 fusion proteins in liposomes
      revealed a heptameric stoichiometry. The oligomerization of p7 protein was then
      confirmed by SDS-PAGE and mass spectrometry analysis of pure, concentrated FLAG
      p7. The same protein was also confirmed to function as an ion channel in
      suspended lipid bilayers and was inhibited by amantadine. These data validate
      this system as a means of generating high resolution structural information on
      the p7 ion channel complex.

PMID- 17032657
TI  - Single strand annealing and ATP-independent strand exchange activities of yeast
      and human DNA2: possible role in Okazaki fragment maturation.
AB  - The Dna2 protein is a multifunctional enzyme with 5'-3' DNA helicase, DNA
      dependent ATPase, 3' exo/endonuclease, and 5' exo/endonuclease. The enzyme is
      highly specific for structures containing single-stranded flaps adjacent to
      duplex regions. We report here two novel activities of both the yeast and human
      Dna2 helicase/nuclease protein: single strand annealing and ATP-independent
      strand exchange on short duplexes. These activities are independent of
      ATPase/helicase and nuclease activities in that mutations eliminating either
      nuclease or ATPase/helicase do not inhibit strand annealing or strand exchange.
      ATP inhibits strand exchange. A model rationalizing the multiple catalytic
      functions of Dna2 and leading to its coordination with other enzymes in
      processing single-stranded flaps during DNA replication and repair is presented.

PMID- 17032658
TI  - Conditional Akt activation promotes androgen-independent progression of prostate
      cancer.
AB  - Aggressive androgen-independent (also termed as hormone-refractory) prostate
      cancer is a major clinical obstacle because there is no means to cure. Previous
      studies have shown that Akt activation is associated with prostate cancer
      progression from androgen-dependent to androgen-independent stage. However, its
      causative role in this process has not been established. One of the major
      limitations is the lack of a well-controlled inducible system to study Akt
      involvement. Recently, we developed a novel inducible Akt (iAKT) system based on
      a chemically induced dimerization (CID) approach. This system allows for
      conditional activation of Akt in a physiological setting. Utilizing this iAKT
      system, we found that Akt activation prevented cell death after serum withdrawal
      and promoted cell proliferation in the absence of androgen in vitro in human
      prostate cancer LNCaP cells, which should stop growing after androgen withdrawal
      or even die after serum starvation. The iAKT-induced death protection and growth
      promotion were further demonstrated in vivo using a transgenic mouse model that
      expresses the iAKT system conditionally in the prostate epithelium. Most
      importantly, in a mouse xenograft model derived from LNCaP cells, iAKT activation
      promoted tumor growth in castrated animals by enhancing cell proliferation and
      inhibiting apoptosis. Taken together, our data suggest that Akt activation is
      playing a causative role in androgen-independent progression of prostate cancer.
      This study provides a significant relevance of Akt-targeted therapy for hormone
      refractory prostate cancers.

PMID- 17032659
TI  - Soy isoflavonoid effects on endogenous estrogen metabolism in postmenopausal
      female monkeys.
AB  - Endogenous estrogens are important determinants of breast cancer risk in
      postmenopausal women. In this study we evaluated the effects of dietary soy
      isoflavonoids on endogenous estrogen metabolism in a postmenopausal primate
      model. Ovariectomized female cynomolgus monkeys were randomized to receive one of
      three diets for 36 months: (i) isoflavonoid-depleted soy protein isolate (SPI-)
      (n = 29); (ii) soy protein isolate with 129 mg isoflavonoids/1800 kcal diet (8.6
      mg isoflavonoids/kg body weight (BW), expressed in aglycone units) (SPI+) (n =
      29) or (iii) isoflavonoid-depleted soy protein isolate with conjugated equine
      estrogens (CEE) at a dose of 0.625 mg/1800 kcal diet (0.042 mg CEE/kg BW) (n =
      30). Mean plasma isoflavonoid concentrations in the SPI+ group were 946.9 +/-
      135.9 nmol/l, and equol was the primary circulating isoflavonoid (549.7 +/- 61.6
      nmol/l). The SPI+ diet resulted in lower serum estrone (E(1)) after 29 (-26%, P =
      0.03) and 34 months (-21%, P = 0.04) compared to the SPI- diet, while urinary 2
      hydroxyestrone (P = 0.005) and the 2 to 16alpha-hydroxyestrone ratio (P < 0.0001)
      were markedly higher in the SPI+ group compared to SPI-. Isoflavonoid treatment
      did not significantly alter gene markers of estrogen metabolism or estrogen
      receptor agonist activity in breast tissue. Within the SPI+ group, higher
      concentrations of serum equol (but not daidzein or genistein) corresponded to
      significantly lower serum E(1), mammary gland epithelial area and uterine weight
      (P < 0.01 for all). These findings suggest that long-term exposure to soy
      isoflavonoids, equol in particular, may facilitate endogenous estrogen clearance
      and catabolism to more benign 2-hydroxylated metabolites.

PMID- 17032660
TI  - Effects of chronic angiotensin II receptor antagonist and angiotensin-converting
      enzyme inhibitor treatments on neurohormonal levels and haemodynamics during
      cardiopulmonary bypass.
AB  - BACKGROUND: Chronic treatment with renin-angiotensin system (RAS) antagonists
      frequently causes deleterious hypotension during anaesthesia. We compared the
      effects of angiotensin II receptor antagonists (ARA) and angiotensin-converting
      enzyme inhibitors (ACEI) on neurohormonal levels and haemodynamics during
      cardiopulmonary bypass (CPB). METHODS: Forty-four patients undergoing mitral
      valvular surgery who were treated with either ARA (ARA group, n=14) or ACEI (ACEI
      group, n=15) over 12 weeks or who were not treated with any RAS antagonist
      (control group, n=15) were enrolled. The plasma levels of epinephrine,
      norepinephrine, arginine vasopressin (AVP) and angiotensin II, and haemodynamic
      variables were measured before (T1) and 15 min after (T2) the start of CPB,
      before aortic unclamping (T3) and at skin closure (T4). Mean arterial pressure
      (MAP) was maintained above 60 mm Hg with phenylephrine administration during CPB.
      RESULTS: The plasma epinephrine, norepinephrine, AVP and angiotensin II levels
      increased during CPB in all groups. Compared with the control group, the AVP
      level was lower at T1 in the ARA group and at T2 in the ARA and ACEI groups. The
      angiotensin II level was higher at T1, T2 and T3 in ARA group compared with ACEI
      and control groups. There were no significant differences in the epinephrine and
      norepinephrine levels among the three groups. The amount of administered
      phenylephrine during CPB was greater and MAP was lower in the ARA group compared
      with the ACEI and control groups. CONCLUSIONS: Chronic ARA treatment resulted in
      more profound hypotension than ACEI treatment during CPB, and this may be
      associated with the blockade of angiotensin II receptors by ARA.

PMID- 17032661
TI  - The effects of propofol on neutrophil function, lipid peroxidation and
      inflammatory response during elective coronary artery bypass grafting in patients
      with impaired ventricular function.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass
      elicits a potent reperfusion injury and inflammatory response, more intense in
      patients with impaired myocardial function. Propofol has antioxidant properties
      which may attenuate such a response. METHODS: In total, 27 patients with impaired
      left ventricular function undergoing CABG were randomly allocated to receive
      either target-controlled infusion propofol (P) or saline (S) immediately before
      aortic cross-clamp release until 4 h after reperfusion. Troponin-I, Urinary 8-epi
      PGF-2alpha isoprostane, coronary sinus and systemic malondialdehyde
      concentrations, Interleukin-6 (IL-6), -8 and -10 concentrations and leucocytes
      function studies (neutrophil respiratory burst, phagocytosis, CD-11b and CD-18
      expression) were measured. RESULTS: Propofol decreased MDA coronary sinus
      concentration at 1, 3 and 5 min after reperfusion (P<0.01); 60 min after
      reperfusion a significant difference between the two groups in systemic MDA
      concentrations was also seen. IL-6 concentration increases were significantly
      greater in Group S than Group P, 4 h after reperfusion [1118 (1333) pg ml(-1) vs
      228 (105) pg ml(-1), P<0.01]. Serum IL-8 concentrations did not increase
      significantly in either group. Compared with baseline values IL-10 concentrations
      decreased after reperfusion but the values were higher in the propofol group than
      in the control group [22 (16) vs 11 (4) pg ml(-1), P<0.05]. No difference in
      leucocyte function or urinary isoprostane concentrations was demonstrated.
      CONCLUSION: Propofol attenuates free-radical-mediated lipid peroxidation and
      systemic inflammation in patients with impaired myocardial function undergoing
      CABG.

PMID- 17032662
TI  - Continuous peripheral nerve block in combat casualties receiving low-molecular
      weight heparin.
AB  - BACKGROUND: Continuous peripheral nerve block (CPNB) is an important therapeutic
      tool in the anaesthetic and analgesic management of combat casualties at Walter
      Reed Army Medical Center (WRAMC). We describe our experience using CPNB
      techniques in combat trauma patients treated with low-molecular weight heparin
      (LMWH). Guidelines used at our institution for managing CPNB catheters in
      patients being treated with LMWH are introduced. METHODS: From March 2003 to
      April 2005, 187 combat casualties treated by the WRAMC regional anaesthesia/acute
      pain section using CPNB were evaluated retrospectively by electronic chart
      review. Patient characteristic data, CPNB type, duration of CPNB, indication for
      LMWH [enoxaparin sodium injection (Lovenox-Sanofi Aventis, Bridgewater, NJ,
      USA)], enoxaparin dose (mg) before and after catheter insertion and removal, time
      from CPNB placement and removal to enoxaparin dose, and complications were
      recorded. RESULTS: Median enoxaparin dose and time given before catheter
      insertion were 30 mg and 21 h, respectively. Median enoxaparin dose was also 30
      mg given a median of 12 h after peripheral nerve catheter placement. Catheters
      remained in situ for a median of 8 days (range 1-33 days). Catheter specific
      complications were infrequent and identified in 7 (3.7%) patients (two catheter
      malfunction-kinking, catheter tip dislodgement in situ, two superficial catheter
      site infections and two catheter dislocations). There were no catheter-related
      bleeding complications evident in this study. CONCLUSIONS: Information regarding
      the safety of CPNB in patients treated with LMWH for perioperative venous
      thromboembolism prevention is scarce. Our initial experience with CPNB and
      concurrent LMWH has not been complicated by catheter-related bleeding.

PMID- 17032663
TI  - Modelling: a core technique in anaesthesia and critical care research.

PMID- 17032665
TI  - Factors in epidural haematoma.

PMID- 17032664
TI  - Propofol and memory.

PMID- 17032666
TI  - Useful ectopics.

PMID- 17032667
TI  - Facilitated insertion of a nasogastric tube in tracheal intubated patients using
      the GlideScope.

PMID- 17032668
TI  - Epidural anaesthesia for laparoscopic cholecystectomy in a patient with
      scleroderma.

PMID- 17032669
TI  - Strong magnesium solution.

PMID- 17032670
TI  - Life-threatening spontaneous intracranial hypotension responding to epidural
      blood patch.

PMID- 17032671
TI  - Abdominal surgery, morbid obesity, age, dexamethasone, diabetes mellitus and
      glucose metabolism.

PMID- 17032672
TI  - Mutagenic activities and physicochemical properties of selected
      nitrobenzanthrones.
AB  - Mutagenic activity of nine nitro derivatives of benzanthrone, namely 1-nitro-, 2
      nitro-, 3-nitro-, 9-nitro-, 11-nitro-, 1,9-dinitro-, 3,9-dinitro-, 3,11-dinitro-
      and 3,9,11-trinitrobenzanthrone were tested with Salmonella strains TA98, TA100,
      YG1021 and YG1024 in both the presence and absence of an S9 mix. Each compound
      exhibited mutagenic activity with all the strains. Among these nine isomers, 3
      nitrobenzantrone exhibited the most mutagenic activity with all the strains
      without the S9 mix. The mutagenic activities of the dinitro and trinitro
      derivatives of benzanthrone were lower than that of the 3-nitro derivative; this
      is evident from the mutagenic activity of nitrated polyaromatic hydrocarbons
      (PAH), which is generally enhanced with an increase in nitration. The
      physicochemical properties of nitrated benzanthrone (reduction potential,
      hydrophobicity and orientation of nitro groups to the aromatic ring) demonstrated
      that mononitrated benzanthrone exhibits a lower reduction potential than
      mononitroPAHs such as 1-nitropyrene and 3-nitrofluoranthene, but was almost
      equivalent to that of dinitroPAH. Moreover, the mutagenic activity of
      mononitrobenzanthrones clearly depend on the reduction potential of each
      compound; however, this tendency was not observed in polynitrobenzanthrones,
      probably because the reduction of the nitro groups to amino groups of
      polynitrated benzanthrone might be predominant without a sufficient formation of
      corresponding hydroxyamines. These results suggest that aromatic compounds that
      contain keto groups, when nitrated, may act as potentially powerful direct-acting
      mutagens.

PMID- 17032673
TI  - Evaluating the performance of microarray segmentation algorithms.
AB  - MOTIVATION: Although numerous algorithms have been developed for microarray
      segmentation, extensive comparisons between the algorithms have acquired far less
      attention. In this study, we evaluate the performance of nine microarray
      segmentation algorithms. Using both simulated and real microarray experiments, we
      overcome the challenges in performance evaluation, arising from the lack of
      ground-truth information. The usage of simulated experiments allows us to analyze
      the segmentation accuracy on a single pixel level as is commonly done in
      traditional image processing studies. With real experiments, we indirectly
      measure the segmentation performance, identify significant differences between
      the algorithms, and study the characteristics of the resulting gene expression
      data. RESULTS: Overall, our results show clear differences between the
      algorithms. The results demonstrate how the segmentation performance depends on
      the image quality, which algorithms operate on significantly different
      performance levels, and how the selection of a segmentation algorithm affects the
      identification of differentially expressed genes. AVAILABILITY: Supplementary
      results and the microarray images used in this study are available at the
      companion web site http://www.cs.tut.fi/sgn/csb/spotseg/

PMID- 17032674
TI  - Large scale data mining approach for gene-specific standardization of microarray
      gene expression data.
AB  - MOTIVATION: The identification of the change of gene expression in multifactorial
      diseases, such as breast cancer is a major goal of DNA microarray experiments.
      Here we present a new data mining strategy to better analyze the marginal
      difference in gene expression between microarray samples. The idea is based on
      the notion that the consideration of gene's behavior in a wide variety of
      experiments can improve the statistical reliability on identifying genes with
      moderate changes between samples. RESULTS: The availability of a large collection
      of array samples sharing the same platform in public databases, such as NCBI GEO,
      enabled us to re-standardize the expression intensity of a gene using its mean
      and variation in the wide variety of experimental conditions. This approach was
      evaluated via the re-identification of breast cancer-specific gene expression. It
      successfully prioritized several genes associated with breast tumor, for which
      the expression difference between normal and breast cancer cells was marginal and
      thus would have been difficult to recognize using conventional analysis methods.
      Maximizing the utility of microarray data in the public database, it provides a
      valuable tool particularly for the identification of previously unrecognized
      disease-related genes. AVAILABILITY: A user friendly web-interface
      (http://compbio.sookmyung.ac.kr/~lage/) was constructed to provide the present
      large-scale approach for the analysis of GEO microarray data (GS-LAGE server).

PMID- 17032675
TI  - KGraph: a system for visualizing and evaluating complex genetic associations.
AB  - The KGraph is a data visualization system that has been developed to display the
      complex relationships between the univariate and bivariate associations among an
      outcome of interest, a set of covariates, and a set of genetic factors, such as
      single nucleotide polymorphisms (SNPs). It allows for easy viewing and
      interpretation of genetic associations, correlations among covariates and SNPs,
      and information about the replication and cross-validation of the associations.
      The KGraph allows the user to more easily investigate multicollinearity and
      confounding through visualization of the multidimensional correlation structure
      underlying genetic associations. It emphasizes gene-environment and gene-gene
      interaction, both important components of any genetic system that are often
      overlooked in association frameworks. AVAILABILITY:
      http://www.epidkardia.sph.umich.edu/software/kgrapher

PMID- 17032676
TI  - Robust method for detecting differential gene expression in twin studies.
AB  - MOTIVATION: A steadily increasing number of experiments with microarrays
      stimulate the further development of the statistical methods of the analysis of
      gene expression data. One of the central problems in this area is detecting
      differential gene expression under two or more conditions. Unfortunately, up to
      now it has not been studied how the correlations between related individuals,
      such as twins influence the estimates of differential gene expression. RESULTS:
      In this paper, we discuss this problem and propose a new method that is robust
      with respect to correlations of gene expression data for twins.

PMID- 17032677
TI  - ChromoScan: a scan statistic application for identifying chromosomal regions in
      genomic studies.
AB  - ChromoScan is an implementation of a genome-based scan statistic that detects
      genomic regions, which are statistically significant for targeted measurements,
      such as genetic associations with disease, gene expression profiles, DNA copy
      number variations, as well as other genome-based measurements. A Java graphic
      user interface (GUI) is provided to allow users to select appropriate data
      transformations and thresholds for defining the significant events. AVAILABILITY:
      ChromoScan is freely available from
      http://www.epidkardia.sph.umich.edu/software/chromoscan/

PMID- 17032678
TI  - DASS: efficient discovery and p-value calculation of substructures in unordered
      data.
AB  - MOTIVATION: Pattern identification in biological sequence data is one of the main
      objectives of bioinformatics research. However, few methods are available for
      detecting patterns (substructures) in unordered datasets. Data mining algorithms
      mainly developed outside the realm of bioinformatics have been adapted for that
      purpose, but typically do not determine the statistical significance of the
      identified patterns. Moreover, these algorithms do not exploit the often modular
      structure of biological data. RESULTS: We present the algorithm DASS (Discovery
      of All Significant Substructures) that first identifies all substructures in
      unordered data (DASS(Sub)) in a manner that is especially efficient for modular
      data. In addition, DASS calculates the statistical significance of the identified
      substructures, for sets with at most one element of each type (DASS(P(set))), or
      for sets with multiple occurrence of elements (DASS(P(mset))). The power and
      versatility of DASS is demonstrated by four examples: combinations of protein
      domains in multi-domain proteins, combinations of proteins in protein complexes
      (protein subcomplexes), combinations of transcription factor target sites in
      promoter regions and evolutionarily conserved protein interaction subnetworks.
      AVAILABILITY: The program code and additional data are available at
      http://www.fli-leibniz.de/tsb/DASS

PMID- 17032679
TI  - Integration of gel-based proteome data with pProRep.
AB  - pProRep is a web application integrating electrophoretic and mass spectral data
      from proteome analyses into a relational database. The graphical web-interface
      allows users to upload, analyse and share experimental proteome data. It offers
      researchers the possibility to query all previously analysed datasets and can
      visualize selected features, such as the presence of a certain set of ions in a
      peptide mass spectrum, on the level of the two-dimensional gel. AVAILABILITY: The
      pProRep package and instructions for its use can be downloaded from
      http://www.ptools.ua.ac.be/pProRep. The application requires a web server that
      runs PHP 5 (http://www.php.net) and MySQL. Some (non-essential) extensions need
      additional freely available libraries: details are described in the installation
      instructions.

PMID- 17032680
TI  - Survival analysis of longitudinal microarrays.
AB  - MOTIVATION: The development of methods for linking gene expressions to various
      clinical and phenotypic characteristics is an active area of genomic research.
      Scientists hope that such analysis may, for example, describe relationships
      between gene function and clinical events such as death or recovery. Methods are
      available for relating gene expression to measurements that are categorized or
      continuous, but there is less work in relating expressions to an observed event
      time such as time to death, response or relapse. When gene expressions are
      measured over time, there are methods for differentiating temporal patterns.
      However, methods have not yet been proposed for the survival analysis of
      longitudinally collected microarrays. RESULTS: We describe an approach for the
      survival analysis of longitudinal gene expression data. We construct a measure of
      association between the time to an event and gene expressions collected over
      time. Statistical significance is addressed using permutations and control of the
      false discovery rate. Our proposed method is illustrated on a dataset from a
      multi-center research study of inflammation and response to injury that aims to
      uncover the biological reasons why patients can have dramatically different
      outcomes after suffering a traumatic injury (www.gluegrant.org).

PMID- 17032681
TI  - Meisetz and the birth of the KRAB motif.
AB  - The largest family of transcription factors in mammals is of Cys(2)His(2) zinc
      finger-proteins, each with an NH(2)-terminal KRAB motif. Extensive expansions of
      this family have occurred in separate mammalian lineages, with approximately 400
      such genes known in the human genome. Despite their widespread occurrence, the
      evolutionary provenance of the KRAB motif is unclear since previously it has not
      been found outside of the tetrapod vertebrates. Here, we show that homologues of
      the histone methyltransferase Meisetz are present within the sea urchin
      (Strongylocentrotus purpuratus) genome. Sea urchin and mammalian Meisetz
      sequences each contain an N-terminal KRAB motif, which thereby establishes an
      early origin of the KRAB motif prior to the divergence of echinoderm and chordate
      lineages. Finally, we present evidence that KRAB motifs derive from a novel
      family of KRI (KRAB Interior) motifs that were present in the last common
      ancestor of animals, plants and fungi.

PMID- 17032682
TI  - Identifying cis-regulatory modules by combining comparative and compositional
      analysis of DNA.
AB  - MOTIVATION: Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a
      challenging computational task. Commonly used methods to predict CRMs based on
      the signal of transcription factor binding sites (TFBS) are limited by prior
      information about transcription factor specificity. More general methods that
      bypass the reliance on TFBS models are needed for comprehensive CRM prediction.
      RESULTS: We have developed a method to predict CRMs called CisPlusFinder that
      identifies high density regions of perfect local ungapped sequences (PLUSs) based
      on multiple species conservation. By assuming that PLUSs contain core TFBS motifs
      that are locally overrepresented, the method attempts to capture the expected
      features of CRM structure and evolution. Applied to a benchmark dataset of CRMs
      involved in early Drosophila development, CisPlusFinder predicts more annotated
      CRMs than all other methods tested. Using the REDfly database, we find that some
      'false positive' predictions in the benchmark dataset correspond to recently
      annotated CRMs. Our work demonstrates that CRM prediction methods that combine
      comparative genomic data with statistical properties of DNA may achieve
      reasonable performance when applied genome-wide in the absence of an a priori set
      of known TFBS motifs. AVAILABILITY: The program CisPlusFinder can be downloaded
      at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All
      software is licensed under the Lesser GNU Public License (LGPL).

PMID- 17032683
TI  - COPASI--a COmplex PAthway SImulator.
AB  - MOTIVATION: Simulation and modeling is becoming a standard approach to understand
      complex biochemical processes. Therefore, there is a big need for software tools
      that allow access to diverse simulation and modeling methods as well as support
      for the usage of these methods. RESULTS: Here, we present COPASI, a platform
      independent and user-friendly biochemical simulator that offers several unique
      features. We discuss numerical issues with these features; in particular, the
      criteria to switch between stochastic and deterministic simulation methods,
      hybrid deterministic-stochastic methods, and the importance of random number
      generator numerical resolution in stochastic simulation. AVAILABILITY: The
      complete software is available in binary (executable) for MS Windows, OS X, Linux
      (Intel) and Sun Solaris (SPARC), as well as the full source code under an open
      source license from http://www.copasi.org.

PMID- 17032684
TI  - Structural genomics meets computational biology.

PMID- 17032685
TI  - APDB: a web server to evaluate the accuracy of sequence alignments using
      structural information.
AB  - The APDB webserver uses structural information to evaluate the alignment of
      sequences with known structures. It returns a score correlated to the overall
      alignment accuracy as well as a local evaluation. Any sequence alignment can be
      analyzed with APDB provided it includes at least two proteins with known
      structures. Sequences without a known structure are simply ignored and do not
      contribute to the scoring procedure. AVAILABILITY: APDB is part of the T-Coffee
      suite of tools for alignment analysis, it is available on www.tcoffee.org. A
      stand-alone version of the package is also available as a freeware open source
      from the same address.

PMID- 17032688
TI  - Improvement of left ventricular diastolic function after alcohol septal ablation
      for obstructive hypertrophic cardiomyopathy? Yes, of course, but...

PMID- 17032686
TI  - Administration of efavirenz (600 mg/day) with rifampicin results in highly
      variable levels but excellent clinical outcomes in patients treated for
      tuberculosis and HIV.
AB  - OBJECTIVES: Pharmacokinetic interactions between rifampicin and antiretroviral
      therapy (ART), including efavirenz, are problematic and need to be better defined
      to determine proper dose and to be correlated with short-term and long-term
      clinical outcomes. PATIENTS AND METHODS: Consenting patients with smear-positive
      pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600
      mg), with rifampicin-containing TB regimen by directly observed therapy and self
      administration at TB therapy completion. Trough efavirenz levels were measured by
      HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV
      and TB outcomes were monitored. RESULTS: Twenty African patients were enrolled
      [15 female, mean age 31 years, baseline weight 59.4 kg (range 45-97), viral load
      5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations
      were available from 19 patients (58 on, 14 after rifampicin). The geometric mean
      efavirenz concentration was 1730 ng/mL (range 354-27,179) on and 1377 ng/mL
      (range 572-3975) off rifampicin (P = 0.55). Inter-subject variability in
      efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with
      relatively consistent intra-subject variation over time (median CV 24%). Over
      half of patients had efavirenz concentrations above or below the expected
      therapeutic range (1000-4000 ng/mL). Efavirenz levels were not predicted by
      weight or gender and were not associated with HIV clinical outcomes. Overall 80%
      of patients had non-detectable viral loads at 6 months and 65% at 21 months with
      a cumulative CD4 cell increase of 196 cells/mm3. CONCLUSIONS: In this
      longitudinal study, despite wide variability in plasma efavirenz concentrations
      during rifampicin administration, excellent clinical outcomes were obtained. In
      African patients treated for HIV and TB, our data support the routine use of
      efavirenz at 600 mg/day when receiving rifampicin.

PMID- 17032687
TI  - Evaluation of a regional disease management programme for patients with asthma or
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To assess the impact of a population-based disease management
      programme for adult patients with asthma or chronic obstructive pulmonary disease
      (COPD) on process measures, intermediate outcomes, and endpoints of care. DESIGN:
      Quasi-experimental design with 12-month follow-up. SETTING: Region of Maastricht
      (the Netherlands) including university hospital and 16 general practices.
      PARTICIPANTS: Nine hundred and seventy-five patients of whom 658 have asthma and
      317 COPD. INTERVENTION: Disease management programme. MAIN OUTCOME MEASURE(S):
      Endpoints of care are respiratory health, health utility, patient satisfaction,
      and total health care costs related to asthma or COPD. RESULTS: Quality aspects
      of care, disease control, self-care behaviour, smoking status, disease-specific
      knowledge, and patients' satisfaction improved after implementation of the
      programme. Lung function was not affected by implementation of the programme. For
      COPD patients, a significant improvement in health utility was found. For
      patients with asthma, significant cost savings were measured. CONCLUSIONS:
      Organizing health care according to principles of disease management for adults
      with asthma or COPD is associated with significant improvements in several
      processes and outcomes of care, while costs of care do not exceed the existing
      budget.

PMID- 17032689
TI  - The high cost of implantable defibrillators.
AB  - Increased use of ICDs in patients with cardiac disease has the potential to
      strain national health care budgets because of the large numbers of eligible
      patients and the high cost of the ICDs. Randomized trials show ICDs increase life
      expectancy in some groups of patients and also increase total medical costs
      significantly. ICDs exemplify the role of new technology as the main force behind
      rising health care costs. ICDs have not been used in all eligible patients, in
      part because of cost, but also because of patient resistance and a shortage of
      specialists able to implant and manage complex ICDs. The cost-effectiveness of
      ICDs would be improved by development of simpler and cheaper devices, and by
      better tools to identify patients who benefit from an ICD.

PMID- 17032690
TI  - Clinical and prognostic profile of patients with infective endocarditis who need
      urgent surgery.
AB  - AIMS: Surgery in patients with infective endocarditis (IE) can be elective (upon
      completion of antibiotic treatment) or urgent (before antibiotic treatment has
      ended) when the clinical course is unfavourable. However, urgent surgery for left
      sided endocarditis is associated with high mortality. The aims of this study were
      to describe the profile of patients with left-sided endocarditis who underwent
      urgent surgery and to analyse the factors that predicted mortality. METHODS AND
      RESULTS: Among 508 consecutive episodes of IE, 391 were left-sided and 89
      required urgent surgery. The main reasons for urgent surgery were heart failure
      that did not respond to medication (72%) and persistent infection despite
      appropriate antibiotic treatment (31%). Thirty-two patients (36%) died during
      their hospital stay. Univariate analysis identified renal failure, septic shock,
      Gram-negative bacteria, persistent infection, and surgery for persistent
      infection as factors associated with mortality. Multivariate analysis confirmed
      only persistent infection and renal insufficiency as factors independently
      associated with a poor prognosis. CONCLUSION: Patients with IE who need urgent
      surgery have a poor clinical course. Heart failure, the main cause of urgent
      surgery, was not associated with higher mortality. However, persistent infection
      and renal failure were factors associated with higher post-surgical mortality.

PMID- 17032691
TI  - Prediction of risk of death and myocardial infarction in the six months after
      presentation with acute coronary syndrome: prospective multinational
      observational study (GRACE).
AB  - OBJECTIVE: To develop a clinical risk prediction tool for estimating the
      cumulative six month risk of death and death or myocardial infarction to
      facilitate triage and management of patients with acute coronary syndrome.
      DESIGN: Prospective multinational observational study in which we used
      multivariable regression to develop a final predictive model, with prospective
      and external validation. SETTING: Ninety four hospitals in 14 countries in
      Europe, North and South America, Australia, and New Zealand. POPULATION: 43,810
      patients (21,688 in derivation set; 22,122 in validation set) presenting with
      acute coronary syndrome with or without ST segment elevation enrolled in the
      global registry of acute coronary events (GRACE) study between April 1999 and
      September 2005. MAIN OUTCOME MEASURES: Death and myocardial infarction. RESULTS:
      1989 patients died in hospital, 1466 died between discharge and six month follow
      up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors
      independently predicted death and the combined end point of death or myocardial
      infarction in the period from admission to six months after discharge: age,
      development (or history) of heart failure, peripheral vascular disease, systolic
      blood pressure, Killip class, initial serum creatinine concentration, elevated
      initial cardiac markers, cardiac arrest on admission, and ST segment deviation.
      The simplified model was robust, with prospectively validated C-statistics of
      0.81 for predicting death and 0.73 for death or myocardial infarction from
      admission to six months after discharge. The external applicability of the model
      was validated in the dataset from GUSTO IIb (global use of strategies to open
      occluded coronary arteries). CONCLUSIONS: This risk prediction tool uses readily
      identifiable variables to provide robust prediction of the cumulative six month
      risk of death or myocardial infarction. It is a rapid and widely applicable
      method for assessing cardiovascular risk to complement clinical assessment and
      can guide patient triage and management across the spectrum of patients with
      acute coronary syndrome.

PMID- 17032692
TI  - Classification of G-protein coupled receptors at four levels.
AB  - G-protein coupled receptors (GPCRs) are transmembrane proteins which via G
      proteins initiate some of the important signaling pathways in a cell and are
      involved in various physiological processes. Thus, computational prediction and
      classification of GPCRs can supply significant information for the development of
      novel drugs in pharmaceutical industry. In this paper, a nearest neighbor method
      has been introduced to discriminate GPCRs from non-GPCRs and subsequently
      classify GPCRs at four levels on the basis of amino acid composition and
      dipeptide composition of proteins. Its performance is evaluated on a non
      redundant dataset consisted of 1406 GPCRs for six families and 1406 globular
      proteins using the jackknife test. The present method based on amino acid
      composition achieved an overall accuracy of 96.4% and Matthew's correlation
      coefficient (MCC) of 0.930 for correctly picking out the GPCRs from globular
      proteins. The overall accuracy and MCC were further enhanced to 99.8% and 0.996
      by dipeptide composition-based method. On the other hand, the present method has
      successfully classified 1406 GPCRs into six families with an overall accuracy of
      89.6 and 98.8% using amino acid composition and dipeptide composition,
      respectively. For the subfamily prediction of 1181 GPCRs of rhodopsin-like
      family, the present method achieved an overall accuracy of 76.7 and 94.5% based
      on the amino acid composition and dipeptide composition, respectively. Finally,
      GPCRs belonging to the amine subfamily and olfactory subfamily of rhodopsin-like
      family were further analyzed at the type level. The overall accuracy of dipeptide
      composition-based method for the classification of amine type and olfactory type
      of GPCRs reached 94.5 and 86.9%, respectively, while the overall accuracy of
      amino acid composition-based method was very low for both subfamilies. In
      comparison with existing methods in the literature, the present method also
      displayed great competitiveness. These results demonstrate the effectiveness of
      our method on identifying and classifying GPCRs correctly. GPCRsIdentifier, a
      corresponding stand-alone executable program for GPCR identification and
      classification was also developed, which can be acquired freely on request from
      the authors for academic purposes.

PMID- 17032693
TI  - Size-resolved sulfuric acid mist concentrations at phosphate fertilizer
      manufacturing facilities in Florida.
AB  - Strong inorganic acid mists containing sulfuric acid were identified as a 'known
      human carcinogen' in a National Toxicology Program (NTP) report where phosphate
      fertilizer manufacture was listed as one of many occupational exposures to strong
      acids. To properly assess the occupational exposure to sulfuric acid mists in
      modern facilities, approved National Institute for Occupational Safety and Health
      (NIOSH) Method 7903 and a cascade impactor were used for measuring the total
      sulfuric acid mist concentration and size-resolved sulfuric acid mist
      concentration, respectively. Sampling was conducted at eight phosphate fertilizer
      plants and two background sites in Florida and there were 24 sampling sites in
      these plants. Samples were analyzed by ion chromatography (IC) to quantify the
      water-soluble ion species. The highest sulfuric acid concentrations by the
      cascade impactor were obtained at the sulfuric acid pump tank area. When high
      aerosol mass concentrations (100 micro g m(-3)) were observed at this area, the
      sulfuric acid mists were in the coarse mode. The geometric mean sulfuric acid
      concentrations (+/-geometric standard deviation) of PM(23) (aerodynamic cut size
      smaller than 23 micro m), PM(10) and PM(2.5) from the cascade impactor were 41.7
      (+/-5.5), 37.9 (+/-5.8) and 22.1 (+/-4.5) micro g m(-3), respectively. The
      geometric mean (+/-geometric standard deviation) for total sulfuric acid
      concentration from the NIOSH method samples was 143 (+/-5.08) micro g m(-3).
      Sulfuric acid mist concentrations varied significantly among the plants and even
      at the same location. The measurements by the NIOSH method were 1.5-229 times
      higher than those by the cascade impactor. Moreover, using the NIOSH method, the
      sulfuric acid concentrations measured at the lower flow rate (0.30 Lpm) were
      higher than those at the higher flow rate (0.45 Lpm). One possible reason for the
      significant differences between the results from the cascade impactor and the
      NIOSH method is the potential artifact resulting from the interaction of SO(2)
      with silica gel and glass fiber used in the NIOSH method.

PMID- 17032694
TI  - Living near main streets and respiratory symptoms in adults: the Swiss Cohort
      Study on Air Pollution and Lung Diseases in Adults.
AB  - The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA),
      conducted in 1991 (SAPALDIA 1) in eight areas among 9,651 randomly selected
      adults aged 18-60 years, reported associations among the prevalence of
      respiratory symptoms, nitrogen dioxide, and particles with an aerodynamic
      diameter of less than 10 microg/m3. Later, 8,047 subjects reenrolled in 2002
      (SAPALDIA 2). The effects of individually assigned traffic exposures on reported
      respiratory symptoms were estimated, while controlling for socioeconomic and
      exposure- and health-related factors. The risk of attacks of breathlessness
      increased for all subjects by 13% (95% confidence interval: 3, 24) per 500-m
      increment in the length of main street segments within 200 m of the home and
      decreased in never smokers by 12% (95% confidence interval: 0, 22) per 100-m
      increment in distance from home to a main street. Living within 20 m of a main
      street increased the risks of regular phlegm by 15% (95% confidence interval: 0,
      31) and wheezing with breathing problems by 34% (95% confidence interval: 0, 79)
      in never smokers. In 2002, the effects related to road distance were different
      from those in 1991, which could be due to changes in the traffic pollution
      mixture. These findings among a general population provide strong confirmation
      that living near busy streets leads to adverse respiratory health effects.

PMID- 17032695
TI  - Violence and psychiatric morbidity in a national household population--a report
      from the British Household Survey.
AB  - This study measured the prevalence of self-reported violence and associations
      with psychiatric morbidity in a national household population, based on a cross
      sectional survey in 2000 of 8,397 respondents in Great Britain. Diagnoses were
      derived from computer-assisted interviews, with self-reported violent behavior
      over the previous 5 years. The 5-year prevalence of nonlethal violence in Britain
      was 12% (95% confidence interval: 11, 13). The risk of violence was substantially
      increased by alcohol dependence (odds ratio=2.72, 95% confidence interval: 1.85,
      3.98), drug dependence (odds ratio=2.63, 95% confidence interval: 1.45, 4.74),
      and antisocial personality disorder (odds ratio=6.12, 95% confidence interval:
      3.87, 9.66). Low prevalences of these conditions (7%, 4%, and 4%, respectively)
      contrasted with their relatively high proportions of attributed risk of violence
      (23%, 15%, and 15%). Hazardous drinking was associated with 56% of all reported
      violent incidents. Screening positive for psychosis did not independently
      increase risk (odds ratio=3.20, 95% confidence interval: 0.35, 29.6). The study
      concluded that psychiatric morbidity makes a significant public health impact on
      violence exerted primarily by persons with any personality disorder, substance
      dependence, and hazardous drinking. Population interventions for violent behavior
      are appropriate for hazardous drinking as are targeted interventions for
      substance dependence and antisocial personality disorder. Despite public concern,
      the risks of violence from persons with severe mental illness were very low.

PMID- 17032696
TI  - High cumulative risk of lung cancer death among smokers and nonsmokers in Central
      and Eastern Europe.
AB  - The authors have calculated cumulative risks of lung cancer from a case-control
      study conducted between 1998 and 2002 involving 2,633 lung cancer cases and 2,884
      controls in Hungary, Poland, the Czech Republic, Slovakia, Romania, and Russia.
      The odds ratios for smoking history were combined with national lung cancer
      mortality rates to obtain the cumulative risk of lung cancer. The cumulative risk
      of death from lung cancer by the age of 75 years among current male smokers was
      14.6% in Romania and Russia and 15.8% in Poland, similar to levels reported in
      Western Europe, although higher risks were found in the Czech Republic (19.8%),
      Hungary (21.9%), and Slovakia (28.2%). Cumulative risks of lung cancer death
      among never smokers of over 1% were observed in Hungary among both men and women
      and among men in Poland. The effect of quitting smoking on the lifetime
      cumulative risk was substantial, with between 67% and 83% of lung cancer risk
      among men being avoided by quitting before the age of 50 years. This substantial
      reduction in risk among former smokers confirms that lung cancer mortality in
      Central Europe over the next three decades will be determined by the extent to
      which current smokers can successfully quit smoking.

PMID- 17032697
TI  - DAMPs, PAMPs and alarmins: all we need to know about danger.
AB  - Multicellular animals detect pathogens via a set of receptors that recognize
      pathogen-associated molecular patterns (PAMPs). However, pathogens are not the
      only causative agents of tissue and cell damage: trauma is another one. Evidence
      is accumulating that trauma and its associated tissue damage are recognized at
      the cell level via receptor-mediated detection of intracellular proteins released
      by the dead cells. The term "alarmin" is proposed to categorize such endogenous
      molecules that signal tissue and cell damage. Intriguingly, effector cells of
      innate and adaptive immunity can secrete alarmins via nonclassical pathways and
      often do so when they are activated by PAMPs or other alarmins. Endogenous
      alarmins and exogenous PAMPs therefore convey a similar message and elicit
      similar responses; they can be considered subgroups of a larger set, the damage
      associated molecular patterns (DAMPs).

PMID- 17032698
TI  - Mining literature for systems biology.
AB  - Currently, literature is integrated in systems biology studies in three ways.
      Hand-curated pathways have been sufficient for assembling models in numerous
      studies. Second, literature is frequently accessed in a derived form, such as the
      concepts represented by the Medical Subject Headings (MeSH) and Gene Ontologies
      (GO), or functional relationships captured in protein-protein interaction (PPI)
      databases; both of these are convenient, consistent reductions of more complex
      concepts expressed as free text in the literature. Moreover, their contents are
      easily integrated into computational processes required for dealing with large
      data sets. Last, mining text directly for specific types of information is on the
      rise as text analytics methods become more accurate and accessible. These uses of
      literature, specifically manual curation, derived concepts captured in ontologies
      and databases, and indirect and direct application of text mining, will be
      discussed as they pertain to systems biology.

PMID- 17032699
TI  - An informative Bayesian structural equation model to assess source-specific
      health effects of air pollution.
AB  - A primary objective of current air pollution research is the assessment of health
      effects related to specific sources of air particles or particulate matter (PM).
      Quantifying source-specific risk is a challenge because most PM health studies do
      not directly observe the contributions of the pollution sources themselves.
      Instead, given knowledge of the chemical characteristics of known sources,
      investigators infer pollution source contributions via a source apportionment or
      multivariate receptor analysis applied to a large number of observed elemental
      concentrations. Although source apportionment methods are well established for
      exposure assessment, little work has been done to evaluate the appropriateness of
      characterizing unobservable sources thus in health effects analyses. In this
      article, we propose a structural equation framework to assess source-specific
      health effects using speciated elemental data. This approach corresponds to
      fitting a receptor model and the health outcome model jointly, such that
      inferences on the health effects account for the fact that uncertainty is
      associated with the source contributions. Since the structural equation model
      (SEM) typically involves a large number of parameters, for small-sample settings,
      we propose a fully Bayesian estimation approach that leverages historical
      exposure data from previous related exposure studies. We compare via simulation
      the performance of our approach in estimating source-specific health effects to
      that of 2 existing approaches, a tracer approach and a 2-stage approach.
      Simulation results suggest that the proposed informative Bayesian SEM is
      effective in eliminating the bias incurred by the 2 existing approaches, even
      when the number of exposures is limited. We employ the proposed methods in the
      analysis of a concentrator study investigating the association between ST
      segment, a cardiovascular outcome, and major sources of Boston PM and discuss the
      implications of our findings with respect to the design of future PM concentrator
      studies.

PMID- 17032700
TI  - Association of CXCR4 and CCR7 chemokine receptor expression and lymph node
      metastasis in human cervical cancer.
AB  - BACKGROUND: The chemokine receptors CXCR4 and CCR7 have been suggested to play an
      important role in cancer invasion and metastasis. The expression of these
      receptors in human cervical cancer, however, has seldom been characterized.
      PATIENTS AND METHODS: We investigated the expression of CXCR4 and CCR7 in
      cervical cancer specimens and determined the association between their expression
      and the clinicopathological features observed, including patient outcome.
      RESULTS: CXCR4 expression was significantly higher in elderly patients (P=0.025);
      it was also significantly increased in patients with cancers displaying large
      tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space
      involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was
      significantly higher in cases of squamous cell carcinomas (P=0.010) and in
      patients with cancers showing large tumor size (P<0.0001), deep stromal invasion
      (P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement
      (P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis
      revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7
      (P=0.022) expression were independent factors that influenced pelvic lymph node
      metastasis. The disease-free survival and overall survival (OS) rates of patients
      exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001).
      In addition, the expression of both CXCR4 and CCR7 was an independent prognostic
      factor for OS (95% confidence interval=1.03-17.86; P=0.046). CONCLUSIONS: CXCR4
      and CCR7 expression may be associated with lymph node metastasis; moreover, the
      expression of these receptors can serve as an indicator of poor prognosis in
      patients with cervical cancer.

PMID- 17032701
TI  - Toxicokinetics of inhaled trichloroethylene and tetrachloroethylene in humans at
      1 ppm: empirical results and comparisons with previous studies.
AB  - Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have
      been widely used in a variety of industries, and both are widespread
      environmental contaminants. In order to provide a better basis for understanding
      their toxicokinetics at environmental exposures, seven human volunteers were
      exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples
      collected for analysis during exposure and up to 6-days postexposure.
      Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH
      plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in
      blood and urine; TRI and TETRA concentrations were measured in alveolar breath.
      Toxicokinetic time courses and empirical analyses of classical toxicokinetic
      parameters were compared with those reported in previous human volunteer studies,
      most of which involved exposures that were at least 10-fold higher.
      Qualitatively, TRI and TETRA toxicokinetics were consistent with previous human
      studies. Quantitatively, alveolar retention and clearance by exhalation were
      similar to those found previously but blood and urine data suggest a number of
      possible toxicokinetic differences. For TRI, data from the current study support
      lower apparent blood-air partition coefficients, greater apparent metabolic
      clearance, less TCA production, and greater glucuronidation of TCOH as compared
      to previous studies. For TETRA, the current data suggest TCA formation that is
      similar or slightly lower than that of previous studies. Variability and
      uncertainty in empirical estimates of total TETRA metabolism are substantial,
      with confidence intervals among different studies substantially overlapping.
      Relative contributions to observed differences from concentration-dependent
      toxicokinetics and interindividual and interoccasion variability remain to be
      determined.

PMID- 17032702
TI  - Brain manganese accumulation is inversely related to gamma-amino butyric acid
      uptake in male and female rats.
AB  - Iron (Fe) is an essential trace metal involved in numerous cellular processes.
      Iron deficiency (ID) is reported as the most prevalent nutritional problem
      worldwide. Increasing evidence suggests that ID is associated with altered
      neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity.
      Though recent studies have established differences in which the female brain
      responds to ID-related neurochemical alterations versus the male brain, little is
      known about the interactions of dietary ID, Mn exposure, and sex on gamma-amino
      butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided
      into four dietary treatment groups: control (CN), control/Mn supplemented, ID,
      and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly
      significant decrease in Fe concentrations across all brain regions compared to CN
      in both sexes. Both ID and Mn supplementation led to significant accumulation of
      Mn across all brain regions in both sexes. There was no main effect of sex on Fe
      or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of
      dietary intervention on (3)H-GABA uptake. At 4 weeks, there was a significant
      correlation between Fe concentration and (3)H-GABA uptake in male rats (p <
      0.05). At 6 weeks, there was a significant inverse correlation between Mn
      concentration and (3)H-GABA uptake in male and female rats and a postitive
      correlation between Fe concentration and (3)H-GABA uptake in female rats (p <
      0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes,
      with Mn levels affecting GABA uptake in both sexes in a comparable fashion.

PMID- 17032703
TI  - Goal setting frequency and the use of behavioral strategies related to diet and
      physical activity.
AB  - Goal setting is an effective way to focus attention on behavior change.
      Theoretically, frequency of goal setting may indicate the level of commitment to
      diet and physical activity behavior change. Yet, little is known about the
      association between goal setting frequency and use of specific diet or physical
      activity-related strategies. This study examines whether changes in goal setting
      frequency predict changes in use of behavioral strategies over time, controlling
      for baseline strategy use, demographics and whether a person was trying to lose
      weight. Data are from a baseline and 1-year follow-up survey of adults in rural
      Iowa (n = 385). Overall, goal setting frequency was positively associated with
      use of the strategies measured, at baseline and overtime. Frequent goal setting
      that is focused specifically on diet or physical activity was more predictive of
      using dietary or physical activity strategies, respectively, than goal setting
      focused on weight loss overall. The study provides empirical support for what has
      been assumed theoretically, that is, frequent goal setting for weight management
      is an indicator of use of specific behavioral strategies. Significant challenges
      remain in regard to maintenance of this activity and attainment of weight loss
      goals.

PMID- 17032704
TI  - Evaluation of a 2-year physical activity and healthy eating intervention in
      middle school children.
AB  - The aim of the present study was to evaluate the effects of a middle school
      physical activity and healthy eating intervention, including an environmental and
      computer-tailored component, and to investigate the effects of parental
      involvement. A random sample of 15 schools with seventh and eight graders was
      randomly assigned to one of three conditions: (i) intervention with parental
      involvement, (ii) intervention alone and (iii) control group. In 10 schools, an
      intervention, combining environmental changes with computer-tailored feedback,
      was implemented over 2 school years. In five intervention schools, increased
      parental support was added. Physical activity was measured with questionnaires in
      the total sample and with accelerometers in a sub-sample of children. Fat intake,
      fruit, water and soft drink consumption were measured using food-frequency
      questionnaires. Results showed significant positive intervention effects on
      physical activity in both genders and on fat intake in girls. Parental
      involvement did not increase intervention effects. It can be concluded that
      physical activity and eating behaviours of middle school children can be improved
      by school-based strategies combining environmental and personal interventions.
      The use of personalized computer-tailored interventions seems to be a promising
      tool for targeting adolescents but needs to be further explored.

PMID- 17032705
TI  - Effects of tailoring health messages on physical activity.
AB  - Computer-tailored printed education can be a promising way of promoting physical
      activity. The present study tested whether computer-tailored feedback on physical
      activity is effective and whether there are differences between respondents with
      low and high motivation to change. Respondents (n = 487) were randomly assigned
      to a tailored intervention group or a no information control group. Physical
      activity and determinants were measured at baseline and after 3 months. At post
      test, the motivated respondents in the control group were more likely not to meet
      the recommendation for physical activity than to meet it, and motivated
      respondents in the experimental group were more likely to engage in transport
      related activities and showed more improvement over time for the total activity
      score than respondents in the control group (beta = 0.24, P = 0.02). Both groups
      improved their behaviour over time. No group differences in physical activity
      were found for the unmotivated respondents. The results showed that the effects
      of the tailored feedback were restricted to respondents who had a positive
      motivation to change at baseline. Possible explanations could be that unmotivated
      respondents were unwilling to read and process the information because they felt
      'no need to change'. Alternatively, one tailored feedback letter may not have
      been sufficient for this unmotivated group.

PMID- 17032706
TI  - Is parenting style related to children's healthy eating and physical activity in
      Latino families?
AB  - Parenting styles influence a child's risk for obesity. The goals of this study
      are to evaluate the influence of (i) parenting style on children's health
      behaviors (physical activity and dietary intake), (ii) children's
      sociodemographic characteristics on parenting style and on children's health
      behaviors and (iii) parents' sociodemographic characteristics on their use of
      controlling styles to promote a healthy home environment. Survey and
      anthropometric data were collected from a community sample of Latino parents (n =
      812) and their children in kindergarten through second grade. Parental use of
      positive reinforcement and monitoring was associated with children's healthy
      eating and exercise. Also, parents' use of appropriate disciplining styles was
      associated with healthier eating, while parental use of control styles was
      associated with unhealthy eating. The daughters of parents who used controlling
      styles ate more unhealthy foods than did the sons. Older, employed and more
      acculturated parents used less controlling styles than their counterparts.
      Parenting interventions targeting children's dietary intake and physical activity
      should encourage parents to use more positive reinforcement and monitor their
      children's health behaviors as these parenting styles are associated with
      healthier behaviors. Moreover, intervention researchers may want to encourage
      Latino parents to use less controlling styles with girls as this parenting style
      increased girls' risk for unhealthy eating.

PMID- 17032707
TI  - Evaluation of the training of Korean community health workers for chronic disease
      management.
AB  - The use of community health workers (CHWs) or lay health advisors has been
      increasingly popular as an effective means of secondary prevention for
      cardiovascular health in hard-to-reach, underserved populations. Yet, published
      evaluations of the CHW training programs are rare. The purpose of this article is
      to report the results of an evaluation of a CHW training program for hypertension
      and diabetes management for Korean-American seniors. Forty-eight hours of
      training was developed and delivered to 12 Korean CHWs. Evaluation of the
      training program involved CHW surveys, trainer observation and debriefing and CHW
      focus groups. Testing of CHW knowledge showed that all CHWs met the minimum
      required knowledge level of 70%. Independent ratings by two trainer observations
      revealed that the overall CHW performance was satisfactory. Both CHW ratings and
      focus group data indicated that the training program met their expectation
      (average 9.3 on a 10-point scale) and was successful in empowering them to assume
      their role as a 'health initiator', 'health advertising agent' or 'health role
      model'. While this course is judged to be effective in general, future research
      is warranted to determine whether CHW provision of care and support will affect
      health outcomes in the target population.

PMID- 17032708
TI  - Health promotion for people with disabilities: development and evaluation of the
      Living Well with a Disability program.
AB  - People with disabilities can benefit from health promotion opportunities to
      reduce the incidence and severity of secondary conditions that further limit
      their participation in society. This paper describes participatory action
      research (PAR) methods we used to develop, implement and evaluate the Living Well
      with a Disability program. Community-based agencies that provide information and
      referral services to people with disabilities (independent living centers funded
      under Title VII, Rehabilitation Act) recruited a convenience sample of 246 people
      with mobility impairments to participate in a randomly assigned, wait-list
      control health promotion intervention study. Paper-and-pencil outcome measures
      included the secondary conditions surveillance instrument, unhealthy days and
      health care utilization. Logistic regression on outcomes controlling for
      demographic variables and pre-test measures indicated reductions in all three
      outcome variables. People with mobility impairments who participated in the
      Living Well with a Disability program reported less limitation from secondary
      conditions, fewer unhealthy days and less health care utilization. PAR methods
      are particularly important to design useful interventions for this population.

PMID- 17032710
TI  - The somatotopic organization of cytoarchitectonic areas on the human parietal
      operculum.
AB  - The secondary somatosensory cortex (SII) of nonhuman primates is located on the
      parietal operculum. In the monkey, electrophysiological and connectivity tracing
      studies as well as histological investigations provide converging evidence for 3
      distinct cortical areas (SII, PV, and VS) within this region, each of which
      contains a complete somatotopic map. Although the equivalency of the parietal
      operculum as the location of SII between humans and nonhuman primates is
      undisputed, the internal organization of the human SII region is still largely
      unknown. Based on their topography, we have previously argued that the
      cytoarchitectonic areas OP 1, OP 4, and OP 3 may constitute the human homologues
      of areas SII, PV, and VS, respectively. To test this hypothesis, we here examined
      (using functional magnetic resonance imaging) the somatotopic organization of the
      human parietal operculum by applying tactile stimulation to the skin at 4
      different locations on either side of the body (face, hands, trunk, and legs).
      The locations of the resulting activation foci were then compared with the
      cytoarchitectonic maps of this region. Data analysis revealed 2 somatotopic body
      representations on the lateral operculum in areas OP 1 and OP 4. The functional
      border between these 2 body maps was defined by a mirror reversal in the
      somatotopic arrangement and coincided with the cytoarchitectonically defined
      border between these 2 areas. This somatotopic arrangement closely matches that
      described for SII and PV in nonhuman primates. The data also suggested a third
      somatotopic map located deeper inside the Sylvian fissure in area OP 3. Based on
      the observed topographic arrangement and their functional response
      characteristics, we conclude that cytoarchitectonic areas OP1, OP 4, and OP 3 on
      the human parietal operculum constitute the human homologues of primate areas
      SII, PV, and VS, respectively.

PMID- 17032711
TI  - Thyroid hormone signaling in human ovarian surface epithelial cells.
AB  - CONTEXT: Ovarian surface epithelial (OSE) cells express multiple nuclear hormone
      receptor genes, including those encoding thyroid hormone and estrogen receptors
      (TR and ER, respectively). Ovarian cancer is hormone-dependent, and
      epidemiological evidence links hyperthyroidism, inflammation of the ovarian
      surface, and increased risk of ovarian cancer. OBJECTIVE: The objective of this
      study was to assess T3 action on human OSE cells in vitro, asking 1) is there
      evidence for (pre)receptor control, 2) is T3 inflammatory, and 3) does T3 affect
      ER expression? DESIGN: Immunohistochemical analysis of fixed human ovaries and in
      vitro analysis of human OSE primary cell cultures were performed. PATIENTS:
      Twelve women aged 29-50 yr (median, 41 yr) undergoing elective gynecological
      surgery for nonmalignant conditions were studied. RESULTS: Messenger RNA
      transcripts for TRalpha1, TRalpha2, TRbeta1, and T3 activating deiodinase 2 and
      inactivating deiodinase 3 were present in primary OSE cell cultures by RT-PCR.
      TRalpha and TRbeta proteins were also localized to intact OSE by
      immunohistochemistry. Treatment of OSE cell cultures for 24 h with T3 caused dose
      dependent mRNA expression of inflammation-associated genes: cyclooxygenase-2,
      matrix metalloproteinase-9, and 11betahydroxysteroid dehydrogenase type 1,
      determined by quantitative RT-PCR. Finally, treatment with T3 dose dependently
      stimulated ERalpha mRNA expression without affecting ERbeta1 or ERbeta2.
      CONCLUSION: The ovarian surface is a potential T3 target. T3 exerts direct
      inflammatory effects on OSE cell function in vitro. OSE cell responses to T3
      include increased expression of ERalpha mRNA, which encodes the ER isoform most
      strongly associated with ovarian cancer. This could help explain suggested
      epidemiological links between hyperthyroidism and ovarian cancer.

PMID- 17032712
TI  - An age-related decrease in creatinine clearance is associated with an increase in
      number of falls in untreated women but not in women receiving calcitriol
      treatment.
AB  - CONTEXT: Decreased calcitriol production due to impaired renal function may be a
      significant risk factor for falls in normal aging population. OBJECTIVE: The
      objective of the study was to examine the association between creatinine
      clearance (CrCl) and the incidence of falls and fallers in groups treated with
      placebo, calcitriol, estrogen therapy (ET)/estrogen + progestin therapy (HT), and
      calcitriol + ET/HT. DESIGN: This was a 3-yr, double-blind, placebo-controlled
      study designed to test the efficacy of calcitriol and ET/HT on bone loss and
      falls with analysis by intention to treat and post hoc. SETTING: The study was
      conducted at an academic outpatient center. PARTICIPANTS: Four hundred eighty
      nine normal elderly women aged 65-77 yr; 415 women completed the study.
      INTERVENTION: Subjects were randomized to placebo, calcitriol 0.25 mug twice a
      day, ET daily (conjugated equine estrogens 0.625 mg), HT (conjugated equine
      estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg) and calcitriol + ET/HT.
      MAIN OUTCOME MEASURES: Cumulative number of falls and fallers were compared
      between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater.
      RESULTS: Calcitriol treatment decreased the number of fallers and falls. Low CrCl
      less than 60 ml/min was a predictor of the number of falls per person but not
      fallers in the placebo group (P = 0.007). In the low CrCl group (<60 ml/min), the
      rate of falls decreased on calcitriol by 53% [95% confidence interval (CI) -71%
      to -22%; P = 0.003], calcitriol + ET/HT by 61% (95% CI -76% to -37%; P = 0.001),
      and ET/HT by 25% (95% CI: -55% to +24%; not significant). Calcitriol reduced the
      rate of falls by 30% (95% CI -49% to -4%; P = 0.027) in the CrCl 60 ml/min or
      greater group. CONCLUSION: Calcitriol treatment decreases falls in all subjects
      but especially in elderly women with decreased renal function (<60 ml/min) and
      frequent fallers.

PMID- 17032713
TI  - Detection of thyroid dysfunction in early pregnancy: Universal screening or
      targeted high-risk case finding?
AB  - CONTEXT: Maternal subclinical hypothyroidism during pregnancy is associated with
      various adverse outcomes. Recent consensus guidelines do not advocate universal
      thyroid function screening during pregnancy but recommend testing high-risk
      pregnant women with a personal history of thyroid or other autoimmune disorders
      or with a family history of thyroid disorders. OBJECTIVE: The objective of the
      study was to assess efficacy of the targeted high-risk case-finding approach in
      identifying women with thyroid dysfunction during early pregnancy.
      DESIGN/SETTING: This was a single-center cohort study. PATIENTS/OUTCOME MEASURES:
      We prospectively analyzed TSH, free T4 and free T3 in 1560 consecutive pregnant
      women during their first antenatal visit (median gestation 9 wk). We tested
      thyroperoxidase antibodies in 1327 (85%). We classified 413 women (26.5%), who
      had a personal history of thyroid or other autoimmune disorders or a family
      history of thyroid disorders, as a high-risk group. We examined whether testing
      only such a high-risk group would pick up most pregnant women with thyroid
      dysfunction. RESULTS: Forty women (2.6%) had raised TSH (>4.2 mIU/liter). The
      prevalence of raised TSH was higher in the high-risk group [6.8 vs. 1% in the low
      risk group, relative risk (RR) 6.5, 95% confidence interval (CI) 3.3-12.6, P <
      0.0001]. Presence of personal history of thyroid disease (RR 12.2, 95% CI 6.8-22,
      P < 0.0001) or other autoimmune disorders (RR 4.8, 95% CI 1.3-18.2, P = 0.016),
      thyroperoxidase antibodies (RR 8.4, 95% CI 4.6-15.3, P < 0.0001), and family
      history of thyroid disorders (RR 3.4, 95% CI 1.8-6.2, P < 0.0001) increased the
      risk of raised TSH. However, 12 of 40 women with raised TSH (30%) were in the low
      risk group. CONCLUSION: Targeted thyroid function testing of only the high-risk
      group would miss about one third of pregnant women with overt/subclinical
      hypothyroidism.

PMID- 17032714
TI  - The ghrelin response to exercise before and after growth hormone administration.
AB  - CONTEXT: We have previously shown that exercise-induced GH release is not
      mediated by ghrelin, but it remains to be studied whether the increase in GH may
      suppress postexercise ghrelin levels. OBJECTIVE: The objective of this study was
      to characterize systemic ghrelin levels after exercise with and without
      concomitant GH administration. DESIGN, PARTICIPANTS, AND INTERVENTION: Group A:
      Twenty-nine elite athletes (age, 18-37 yr) were studied after a maximal exercise
      test. Group B: In a double blind, placebo-controlled, parallel study, 32 healthy
      subjects (age, 18-33 yr) were randomized to placebo, GH 0.1 IU/kg per day, or GH
      0.2 IU/kg per day for 4 wk. These subjects performed a multistage fitness test to
      assess maximum oxygen uptake at baseline and after 4 wk. We measured total
      circulating ghrelin levels before and immediately after exercise and at 15, 30,
      60, 90, and 120 min after exercise. RESULTS: Group A: Serum ghrelin levels after
      exercise decreased significantly (P < 0.01). Group B: Exercise at baseline was
      associated with a significant lowering of ghrelin levels after exercise (P <
      0.0001). In addition, 4 wk of high-dose GH were followed by a further
      approximately 20% reduction in basal and after exercise serum ghrelin (micrograms
      per liter): 0.78 (range 0.52-1.17) vs. 0.63 (range 0.50-0.91), P < 0.05.
      CONCLUSIONS: 1) Ghrelin levels decrease significantly after exercise in elite
      athletes and healthy subjects. 2) High-dose GH suppresses ghrelin levels. 3)
      These data support the hypothesis that GH feedback inhibits ghrelin secretion.

PMID- 17032715
TI  - Mild gestational diabetes as a risk factor for congenital cryptorchidism.
AB  - CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal
      diabetes has previously been suggested to be a risk factor for this disorder in
      one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal
      glucose metabolism disorders during pregnancy in newborn boys having normal
      testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of
      maternal history concerning glucose metabolism abnormalities during pregnancy
      among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The
      material of this case-control study comprises 1163 boys with normal testicular
      descent at birth and 125 boys with congenital cryptorchidism. All these singleton
      Finnish boys were born in Turku University Central Hospital (1997-2001) and were
      examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES:
      Information about maternal diabetes diagnosis and abnormality of the result of a
      2-h 75-g oral glucose tolerance test during pregnancy were obtained from the
      hospital records after delivery. RESULTS: After adjustment for possible
      confounding factors, i.e. maternal smoking during pregnancy, maternal age at
      delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for
      gestational age, abnormal maternal glucose metabolism was significantly more
      common in the group of cryptorchid boys [diet-treated gestational diabetes, P =
      0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated
      gestational diabetes or only an abnormal result in oral glucose tolerance test, P
      = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared
      with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose
      metabolism during pregnancy was associated with an increased risk for congenital
      cryptorchidism. The mechanism remains to be elucidated.

PMID- 17032716
TI  - Effectiveness of bone density measurement for predicting osteoporotic fractures
      in clinical practice.
AB  - CONTEXT: Bone density measurement with dual-energy x-ray absorptiometry is widely
      used for fracture risk assessment. It has not been established that published
      gradients of fracture risk from study populations can be directly applied to
      clinical populations. OBJECTIVE: The objective of the study was to assess
      osteoporotic fracture prediction with dual-energy x-ray absorptiometry in a large
      clinical cohort. DESIGN: This was a historical cohort study (mean observation
      period 3.2 +/- 1.5 yr). PATIENTS: The study population was drawn from the
      population-based database of the Manitoba Bone Density Program. Analyses were
      limited to women aged 50 yr or older at baseline (n = 16,505). MAIN OUTCOME
      MEASURE: Each subject's longitudinal health service record was assessed for the
      presence of nontrauma fracture codes (hip, spine, wrist, and humerus) after bone
      density testing. Age-adjusted hazard ratios for fracture were derived from Cox
      proportional hazards models. RESULTS: Site-specific and overall fracture rates
      were significantly associated with each site of bone density measurement (all P <
      0.00001). The 95% confidence intervals overlapped those from a widely cited
      metaanalysis of fracture prediction from different sites. Although fracture
      prediction was not significantly different between the three hip measurement
      sites, each hip site was better than the lumbar spine for predicting overall
      fractures (nonoverlapping 95% confidence intervals). The manufacturer sd
      (equivalent to a unit change in T-score) resulted in a significantly smaller
      gradient of risk for the spine than when the population sd was used. CONCLUSIONS:
      Bone density measurements are effective for predicting fractures in clinical
      practice. However, hip measurements were superior to the spine in overall
      osteoporotic fracture prediction.

PMID- 17032717
TI  - Metabolic profile and body composition in adult women with congenital adrenal
      hyperplasia due to 21-hydroxylase deficiency.
AB  - CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in
      congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular
      disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for
      cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN:
      We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61
      age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were
      30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray
      absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied.
      MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the
      main outcome measures. RESULTS: Younger patients and controls had similar waist
      to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to
      hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls
      but higher than in younger patients. Lipid profiles were slightly more favorable
      in older patients than controls. Gestational diabetes was more common in patients
      (21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension,
      cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most
      patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable
      cardiovascular risk factors were found. Increased fat mass and higher insulin
      levels were, however, found in patients older than 30 yr. High frequency of
      gestational diabetes is a risk marker for future diabetes. Lifelong follow-up,
      lifestyle modifications, and attempts to adjust and reduce the glucocorticoid
      doses seem important.

PMID- 17032718
TI  - 131I activity for remnant ablation in patients with differentiated thyroid
      cancer: A systematic review.
AB  - CONTEXT: Radioiodine ablation of the thyroid remnant after thyroidectomy is
      commonly performed in the management of patients with differentiated thyroid
      cancer. Although many centers administer an activity of 100 mCi, there is
      uncertainty over using a lower activity. OBJECTIVE: A systematic review of the
      published literature was used to compare the success rates of remnant ablation
      using approximately 30 mCi with approximately 100 mCi (1.1 vs. 3.7 GBq). DATA
      SOURCES: Data were obtained from MEDLINE and EMBASE for the years 1966 to March
      2006. STUDY SELECTION: All studies that reported rates of successful ablation
      associated with approximately 30 or approximately 100 mCi of radioiodine were
      reviewed. DATA EXTRACTION: Studies were based on reviews of patient case notes (n
      = 41), prospective cohorts (n = 12), and randomized trials (n = 6). We obtained
      the success of thyroid remnant ablation according to different administered
      activities of radioiodine. Where a study reported on two or more activities, the
      risk ratio of having a successful ablation (approximately 30 vs. approximately
      100 mCi) was calculated and combined in a meta-analysis. DATA SYNTHESIS:
      Observational studies confirmed the high ablation success rate ( approximately
      80%) using approximately 100 mCi, although 22% of studies reported a rate of 90%
      or greater. The pooled ablation success rate in these studies was 10% lower using
      30 mCi compared with 100 mCi (95% confidence interval, 3-17%; P = 0.01). The meta
      analysis of the randomized trials produced equivocal results. For example, the
      rate of successful ablation in patients given 30 mCi was 8% lower compared with
      100 mCi (95% confidence interval, 29% lower or up to 20% greater, P = 0.58),
      consistent with there being no difference or that 30 mCi is much less effective.
      CONCLUSIONS: From the published data, it is not possible to reliably determine
      whether ablation success rates using 30 mCi are similar to using 100 mCi. Large
      randomized trials are needed to resolve the issue and guide clinical practice.

PMID- 17032719
TI  - Vascular endothelial cadherin regulates vascular permeability: Implications for
      ovarian hyperstimulation syndrome.
AB  - CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication
      of treatment with fertility drugs. It is characterized by increased vascular
      permeability and simultaneous overexpression of vascular endothelial growth
      factor (VEGF) in ovarian cells. OBJECTIVE: We tested the hypothesis that the
      endothelium and endothelial cell-to-cell junctions are downstream targets of VEGF
      during OHSS pathogenesis. We investigated the potential involvement of vascular
      endothelial (VE)-cadherin, an interendothelial adhesion molecule, in the
      capillary hyperpermeability in OHSS. DESIGN: Human endothelial cells from
      umbilical veins (HUVEC) were used as an in vitro model of OHSS. INTERVENTION:
      Cell cultures were treated with varying doses of estradiol (E2), human chorionic
      gonadotropin (hCG), VEGF, and antihuman VEGF antibodies, either alone or in
      combination, and the effect on VE-cadherin release was evaluated at different
      time points. Permeability assays were performed using fluoresceinisothiocyanate
      labeled albumin, and actin filaments rearrangement was evaluated by fluorescent
      microscopy. RESULTS: Culturing of HUVEC with high doses of E2 produced no
      significant changes in VE-cadherin concentration, but hCG and VEGF produced a
      significant increase in VE-cadherin release. Time-course experiments showed that
      VE-cadherin was secreted 12 h after VEGF addition. Antihuman VEGF antibodies
      prevented these changes. Permeability assays demonstrated that, although E2 did
      not alter the arrangement of HUVEC in vitro, hCG and VEGF caused changes in the
      actin fibers indicative of increased capillary permeability. VEGF also induced an
      increase in paracellular permeability of HUVEC at the same doses used in the
      previous experiments. CONCLUSIONS: Adhesion molecules like VE-cadherin may play a
      role in the development and progression of increased capillary permeability in
      severe OHSS.

PMID- 17032720
TI  - Prematurity may be a risk factor for thyroid dysfunction in childhood.
AB  - CONTEXT: Children born prematurely and/or small for gestational age (SGA)
      frequently show disturbances in thyroid function. OBJECTIVE: The objective of the
      study was to determine the role played either by size or gestational age on
      subsequent thyroid function. DESIGN AND SETTING: This cross-sectional study was
      conducted at a tertiary referral hospital. PATIENTS: A total of 117 children, 88
      of whom were SGA (mean age 7.8 +/- 2.5 yr) and 29 appropriate for gestational age
      (AGA) (mean age 8.1 +/- 1.9 yr), were selected for the study. MAIN OUTCOME
      MEASURES: We evaluated TSH, free T(4), free T(3), urinary iodine, and antithyroid
      antibodies, and all patients underwent a thyroid ultrasound. Insulin sensitivity
      was assessed with the quantitative insulin sensitivity check index. RESULTS: TSH
      and free T3 were not significantly different in the two groups, whereas free T4
      was higher in the AGA group (P < 0.005). Interestingly, four AGA (13.8%) and 17
      SGA (19.3%) patients had TSH levels above the upper limit of normality. Thyroid
      volume was normal and thyroid autoimmunity was excluded. Urinary iodine was also
      similar in the two groups (115 +/- 66 vs. 143 +/- 87); however, in both groups
      there were some children [15 AGA (51%) and 13 SGA (14.7%) (P < 0.001)] with a
      mild to moderate iodine deficiency. By multiple regression analysis, gestational
      age was found to be the only determinant of TSH serum levels. Insulin sensitivity
      was the same in both groups of children and similar to controls. CONCLUSIONS:
      Some children born prematurely, independently from their birth size, frequently
      have disturbances of the hypothalamus-pituitary-thyroid axis later in life.

PMID- 17032721
TI  - Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery
      of a new risk haplotype.
AB  - CONTEXT: Prior studies of Mexican Americans described association of lipoprotein
      lipase (LPL) gene haplotypes with insulin sensitivity/resistance and
      atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas
      the fourth most common haplotype (haplotype 4) conferred risk for insulin
      resistance and atherosclerosis. OBJECTIVE: In this study of Hispanics in the
      Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL
      haplotype association with insulin sensitivity/resistance. DESIGN: LPL haplotypes
      based on 12 single nucleotide polymorphisms were analyzed for association with
      indexes of insulin sensitivity and other metabolic and adiposity measures.
      SETTING: This study was conducted in the general community of San Antonio, Texas,
      and San Luis Valley, Colorado. PARTICIPANTS: Participants in this study were 978
      members of 86 Hispanic families. MAIN OUTCOME MEASURES: LPL haplogenotype,
      metabolic phenotypes, and adiposity were measured in this study. RESULTS: The
      haplotype structure was identical with that observed in prior studies. Among 978
      phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P
      = 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02)
      and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv
      glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S(I) =
      1.72) and lower with haplotype 4 (S(I)=1.38). Haplotype 2 was associated with
      increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein
      cholesterol ratio, and apolipoprotein B (P = 0.01-0.04). CONCLUSIONS: This study
      independently replicates our prior results of LPL haplotypes 1 and 4 as
      associated with measures of insulin sensitivity and resistance, respectively.
      Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2
      was identified as a new risk haplotype, suggesting the complex nature of LPL's
      effect on features of the insulin resistance syndrome.

PMID- 17032722
TI  - Association of weight gain in infancy and early childhood with metabolic risk in
      young adults.
AB  - CONTEXT: Early postnatal life has been suggested as an important window during
      which risks for long-term health may be influenced. OBJECTIVE: The aim of this
      study was to examine the independent associations between weight gain during
      infancy (0-6 months) and early childhood (3-6 yr) with components of the
      metabolic syndrome in young adults. DESIGN: This was a prospective cohort study
      (The Stockholm Weight Development Study). SETTING: The study was conducted in a
      general community. PARTICIPANTS: Subjects included 128 (54 males) singletons,
      followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults
      met the full criteria for the metabolic syndrome. We therefore calculated a
      continuous clustered metabolic risk score by averaging the standardized values of
      the following components: waist circumference, blood pressure, fasting
      triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level.
      RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain
      during infancy (standardized beta = 0.16; P < 0.0001) but not during early
      childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight,
      gestational age, current height, maternal fat mass, and socioeconomic status at
      age 17 yr. Further adjustment for current fat mass and weight gain during
      childhood did not alter the significant association between infancy weight gain
      with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS:
      Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6
      yr) predicted clustered metabolic risk at age 17 yr. Early interventions to
      moderate rapid weight gain even at very young ages may help to reduce adult
      cardiovascular disease risks.

PMID- 17032723
TI  - Aldosterone-to-renin ratio as a marker for disease severity in 21-hydroxylase
      deficiency congenital adrenal hyperplasia.
AB  - CONTEXT: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency
      (21 OHD) is classified clinically in decreasing order of severity into salt
      wasting, simple-virilizing, and nonclassical forms. Causative mutations in the
      CYP21A2 gene dictate the degrees of adrenal enzyme defect. Salt-wasting crises
      due to aldosterone deficiency are clinically apparent in the salt-wasting form
      but not in other forms of 21 OHD. OBJECTIVES: This study examined the ratio of
      serum aldosterone to plasma renin activity as an index of sodium wasting in
      patients with 21 OHD CAH, heterozygotes, and normal individuals. DESIGN: This was
      a cross-sectional, retrospective, noninterventional study. PATIENTS AND OTHER
      PARTICIPANTS: A total of 402 individuals were included: 224 patients affected
      with 21 OHD CAH and 178 unaffected subjects. Classification into each diagnostic
      group was made primarily on the basis of clinical and hormonal features. Affected
      or unaffected status was confirmed by genotype of CYP21A2. All subjects were on
      ad lib diets without restrictions. Salt-wasting status was examined by sodium
      deprivation testing in 32 salt-wasting subjects and 14 simple virilizing
      subjects. RESULTS: The ratio of serum aldosterone to plasma renin activity was
      found to discriminate well between the different groups of disease severity. The
      lowest ratios, indicative of the least sodium conservation, were seen in the salt
      wasting group with increasing ratios in the simple virilizing, nonclassical, and
      unaffected groups. This ratio remained stable with age. CONCLUSION: The ratio of
      serum aldosterone to plasma renin activity provides a simple index to compare
      groups of patients with varying degrees of 21 OHD.

PMID- 17032725
TI  - A common mitochondrial DNA variant and increased body mass index as associated
      factors for development of type 2 diabetes: Additive effects of genetic and
      environmental factors.
AB  - OBJECTIVE: The suggested correlation between a T-to-C transition at the
      nucleotide 16189 in mitochondrial DNA (mtDNA) with increasing insulin resistance
      and adult-onset diabetes mellitus (DM) is debatable. METHODS: Our study examined
      mtDNA from 462 subjects with type 2 diabetes (T2DM) and 592 normoglycemic
      controls (non-DM). Each participant's body mass index (BMI), fasting plasma
      glucose, fasting insulin concentration, insulin resistance index, and beta-cell
      function were measured. Sequencing for mtDNA, focusing on exploration of the
      hypervariable polycytosine tract within the control region, was also conducted in
      all subjects. RESULTS: Prevalence of the mtDNA 16189 variant was significantly
      different between DM and non-DM subjects (39.2% vs. 30.7% respectively; P =
      0.004). Increased incidence of DM was noted in those harboring the 16189 variant
      compared with those lacking the variant (multivariate odds ratio, 1.38; 95%
      confidence interval, 1.07-1.80). Moreover, increased BMI was identified as an
      aggravating factor for development of DM in subjects harboring the variant. Odds
      ratio determinations yielded 2.14 in overweight and 4.63 in obese subjects
      harboring the variant in comparison with subjects without (1.83 in overweight and
      2.16 in obese subjects). This is consistent with a progressively increased
      prevalence of the mtDNA 16189 variant in the non-DM groups with higher fasting
      insulin concentration, insulin resistance index, and beta-cell function (all
      P(trend) < 0.005). CONCLUSION: The mtDNA 16189 variant can influence development
      of T2DM. The demonstrated dynamic between the 16189 variant and increased BMI
      exemplify an additive effect of genetic and environmental factors on the
      pathogenesis of T2DM.

PMID- 17032724
TI  - Dopamine receptor expression and function in corticotroph ectopic tumors.
AB  - BACKGROUND: Dopamine receptor (DR) expression and dopamine agonist (DA)
      effectiveness have never been demonstrated in neuroendocrine tumors associated
      with ectopic ACTH syndrome (EAS). AIM: The aim of the current study was to
      evaluate DR and particularly D2 subtype expression in neuroendocrine tumors
      associated with EAS and to evaluate the in vivo effectiveness of the DA
      cabergoline in the treatment of EAS. PATIENTS AND METHODS: Six ACTH-secreting
      neuroendocrine tumors, including four lung, one pancreatic, and one thymic
      carcinoid, were used for the evaluation of D2 expression by immunohistochemistry.
      DR subtypes and D2 isoforms and number were evaluated by RT-PCR in three cases of
      persistent EAS after surgery. These patients were treated with cabergoline at the
      dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor
      size were monitored during the treatment period. RESULTS: At
      immunohistochemistry, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was
      confirmed in all three cases but at variable numbers, whereas D4 was expressed in
      two cases. D(2long) was expressed in all three cases, together with D(2short) in
      one case. A normalization of urinary cortisol levels was found in two patients
      (66.7%) after 3 months of treatment. However, treatment escape was demonstrated
      in one of these patients afterward. CONCLUSION: The results of this study
      demonstrated that DR are expressed in neuroendocrine tumors associated with EAS
      and that cabergoline treatment could be effective in controlling cortisol excess
      in a subgroup of patients with EAS. Further studies on a larger number of
      patients are mandatory to confirm the usefulness of DA in EAS.

PMID- 17032726
TI  - Thyroid hormone increases mRNA and protein expression of Na+-K+-ATPase alpha2 and
      beta1 subunits in human skeletal muscles.
AB  - CONTEXT: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent
      skeletal muscles. No study has examined this relationship in human tissues.
      OBJECTIVE: This study investigated the effect of hyperthyroid status on the
      expression of the alpha- and beta-subunits of the Na+-K+-ATPase. DESIGN: The
      vastus lateralis muscles from eight hyperthyroid patients were biopsied before
      and after treatment. Ten age-matched euthyroid subjects served as controls.
      RESULTS: In hyperthyroid patients, the average T3 level was three times higher in
      pretreatment compared with posttreatment (262 +/- 75 vs. 86 +/- 21 ng/dl, P =
      0.001). The relative mRNA expression of the alpha2, but not alpha1 or alpha3,
      subunit was increased approximately 3-fold in pretreatment (2.98 +/- 0.52 vs.
      0.95 +/- 0.40, P < 0.01), whereas that of beta1, not beta2 or beta3, subunit was
      increased approximately 2.8-fold in pretreatment (2.83 +/- 0.38 vs. 1.10 +/-
      0.27, P < 0.01). The relative mRNA expression of the alpha2 and beta1 subunits
      was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P
      = 0.003, respectively). Immunohistochemistry studies revealed an increase in
      protein abundance of the alpha2 and beta1, but not alpha1 or beta2, subunits in
      the plasma membrane of muscle fibers of hyperthyroid patients, which decreased
      after treatment. CONCLUSIONS: This provides the first evidence that, in human
      skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein
      expression at least, in part, at mRNA level, and the alpha2 and beta1 subunits
      play the important role in this regulation.

PMID- 17032727
TI  - Genome-wide patterns of expression in Drosophila pure species and hybrid males.
      II. Examination of multiple-species hybridizations, platforms, and life cycle
      stages.
AB  - Species often produce sterile hybrids early in their evolutionary divergence, and
      some evidence suggests that hybrid sterility may be associated with deviations or
      disruptions in gene expression. In support of this idea, many studies have shown
      that a high proportion of male-biased genes are underexpressed, compared with non
      sex-biased genes, in sterile F1 male hybrids of Drosophila species. In this
      study, we examined and compared patterns of misexpression in sterile F1 male
      hybrids of Drosophila simulans and 2 of its sibling species, Drosophila
      mauritiana and Drosophila sechellia, at both the larval and adult life stages. We
      analyzed hybrids using both commercial Drosophila melanogaster microarrays and
      arrays we developed from reverse transcriptase-polymerase chain reactions of
      spermatogenesis and reproduction-related transcripts from these species (sperm
      array). Although the majority of misexpressed transcripts were underexpressed, a
      disproportionate number of the overexpressed transcripts were located on the X
      chromosome. We detected a high overlap in the genes misexpressed between the 2
      species pairs, and our sperm array was better at detecting such misexpression
      than the D. melanogaster array, suggesting possible weaknesses in the use of an
      array designed from another species. We found only minimal misexpression in the
      larval samples with the sperm array, suggesting that disruptions in
      spermatogenesis occur after this life stage. Further study of these misexpressed
      loci may allow us to identify precisely where disruptions in the spermatogenesis
      pathway occur.

PMID- 17032728
TI  - Characterization of FaRB7, a near root-specific gene from strawberry
      (Fragariaxananassa Duch.) and promoter activity analysis in homologous and
      heterologous hosts.
AB  - Many insect and fungal pathogens posing agronomically important threats
      specifically target the roots in strawberry. The use of a root-specific promoter
      to confer expression of resistance genes in a targeted manner has the potential
      appreciably to benefit the genetic improvement of commercial strawberry
      varieties. A novel gene, FaRB7, was isolated from strawberry (Fragariaxananassa
      Duch.) and found to contain motifs characteristic of tonoplast intrinsic proteins
      (TIPs). Phylogenetic analysis revealed that FaRB7 represents an RB7-type TIP. In
      strawberry, this gene is expressed predominantly in roots, with very low
      expression in petioles. A 2.843 kb region representing the FaRB7 gene upstream
      regulatory sequence was isolated and found to share a number of sequence motifs
      with the promoter of the Nicotiana tabacum TobRB7 root-specific RB7-type TIP.
      When cloned upstream of the gusA reporter gene and introduced into strawberry
      plants, the FaRB7 promoter was shown to direct strong, near root-specific
      expression with expression patterns very similar to that of the endogenous gene.
      Furthermore, the FaRB7 promoter was found to confer constitutive expression,
      comparable to that produced by the cauliflower mosaic virus (CaMV) 35S RNA
      promoter, in tobacco. Thus, the FaRB7 promoter may be used to achieve near-root
      specific transgene expression in strawberry and also represents an alternative to
      the CaMV 35S promoter for producing constitutive foreign gene expression in
      heterologous hosts. The FaRB7 full-length genomic sequence and 5' upstream
      regulatory region have been submitted to the EMBL/GenBank database under
      accession number DQ178022.

PMID- 17032729
TI  - Exploring thermal imaging variables for the detection of stress responses in
      grapevine under different irrigation regimes.
AB  - Temperatures of leaves or canopies can be used as indicators of stomatal closure
      in response to soil water deficit. In 2 years of field experiments with
      grapevines (Vitis vinifera L., cvs Castelao and Aragones), it was found that
      thermal imaging can distinguish between irrigated and non-irrigated canopies, and
      even between deficit irrigation treatments. Average canopy temperature was
      inversely correlated with stomatal conductance measured with a porometer.
      Variation of the distribution of temperatures within canopies was not found to be
      a reliable indicator of stress. A large degree of variation between images was
      found in reference 'wet' and 'dry' leaves used in the first year for the
      calculation of an index proportional to stomatal conductance. In the second year,
      fully irrigated (FI) (100% Et(c)) and non-irrigated (NI) canopies were used as
      alternatives to wet and dry leaves. A crop water stress index utilizing these FI
      and NI 'references', where stressed canopies have the highest values and non
      stressed canopies have the lowest values, was found to be a suitable measure for
      detecting stress. It is suggested that the average temperatures of areas of
      canopies containing several leaves may be more useful for distinguishing between
      irrigation treatments than the temperatures of individual leaves. Average
      temperatures over several leaves per canopy may be expected to reduce the impact
      of variation in leaf angles. The results are discussed in relation to the
      application of thermal imaging to irrigation scheduling and monitoring crop
      performance.

PMID- 17032730
TI  - Low copy number gene transfer and stable expression in a commercial wheat
      cultivar via particle bombardment.
AB  - Two groups of linear gene constructs (gus and bar, and 1Ax1 and bar) lacking
      vector backbone sequences were independently transferred into the elite wheat
      (Triticum aestivum L.) variety EM12, and genetically stable transgenic plants
      with low copy number transgene integration were recovered. Co-transformation
      experiments were carried out in parallel using either circular whole plasmid(s)
      or linear gene cassettes which were purified from the same plasmid by restrictive
      digestion, each cassette consisting of a promoter, an open reading frame, and a
      terminator. Six transgenic wheat lines transformed with 1Ax1 plus bar gene
      cassettes, five lines with gus plus bar gene cassettes, three lines with p1Ax1
      plus pAHC20, and two lines with pAHC25 were regenerated with transformation
      frequencies of 0.6, 0.5, 0.3, and 0.2%, respectively. Southern blotting analysis
      showed that there were 1-4 hybridizing bands in transgenic lines carrying gene
      cassettes, of which most lines displayed single-copy transgene insertion.
      Expression analyses showed that 50.5% of the T1 lines carrying gus plus bar gene
      cassettes have the expression signals of two genes. SDS-PAGE analysis of the T1
      generation revealed that 71% of herbicide-resistant plants carrying 1Ax1 plus bar
      gene cassettes expressed the high molecular weight subunit 1Ax1 in the endosperm.
      Gene cassettes were transmitted and segregated in the subsequent generations, in
      simple Mendelian ratios. In addition, reverse transcription-polymerase chain
      reaction (RT-PCR) results confirmed that 1Ax1 gene cassettes were expressed
      specifically in the endosperm of the transgenic wheat plant. It is proposed that
      gene transfer using multiple gene cassettes offers an efficient and rapid method
      to obtain the single-copy transgenic wheat.

PMID- 17032731
TI  - Differential expression within the LOX gene family in ripening kiwifruit.
AB  - Real-time quantitative PCR was used to study lipoxygenase (LOX) gene expression
      patterns in kiwifruit (Actinidia deliciosa [A. Chev.] C.F. Liang et A.R. Ferguson
      var. deliciosa cv. Hayward) during fruit ripening, and in response to ethylene
      and low temperature during post-harvest storage. Six LOX genes were identified
      and cloned from a kiwifruit EST database. All were expressed in vegetative
      tissues and in the fruit. Expression of AdLox1 and AdLox5 increased markedly as
      fruit developed to the climacteric stage and were up-regulated by ethylene
      treatment, following a similar pattern to LOX enzyme activity. By contrast,
      AdLox2, AdLox3, and AdLox4 transcripts were negatively associated with ethylene
      accumulation, and ethylene application enhanced the decline in transcript levels.
      Transcripts of AdLox6 declined with fruit ripening. The fruit showed no ripening
      changes at low temperature, where transcripts of AdLox1 and AdLox6 were slightly
      induced about 72 h after harvest, suggesting an adaptive response to low
      temperature. Transient expression of the ethylene-responsive AdLox1 gene in
      tobacco leaves led to significant degradation of chlorophyll and promoted tissue
      senescence, whereas AdLox2 had no such effect. The results showed that the six
      LOX genes were differentially regulated during kiwifruit ripening and senescence,
      forming two groups, one active in ripening and responsive to ethylene and the
      other more constitutively expressed. The possible roles of individual LOX
      isoforms in kiwifruit are discussed.

PMID- 17032732
TI  - GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy
      rates in IUI-stimulated cycles. A prospective randomized trial.
AB  - BACKGROUND: Our prospective randomized controlled trial was designed to assess
      whether the use of GnRH antagonists can improve the success rate of controlled
      ovarian stimulation (COS)/intrauterine insemination (IUI) treatments, via
      inhibition of the premature LH rise. METHODS: A total of 104 patients were
      randomly divided, using a randomization list, into two groups: in group A (n =
      52), recombinant FSH (rFSH) was given with GnRH antagonist Cetrorelix, and in
      group B (n = 52), the patients received rFSH alone in a manner similar to that of
      group A. The primary outcome measure was clinical pregnancy rate per couple.
      RESULTS: The pregnancy rate per patient was 53.8% in group A and 30.8% in group B
      (P = 0.017). The rate of premature LH surge was 7% in group A and 35% in group B
      (P < 0.0001). A premature luteinization was observed in two cycles of 144 in
      group A (1.4%) and in 16 cycles of 154 in group B (10.4%) (P = 0.001). The mean
      values of LH and progesterone were significantly lower in patients receiving GnRH
      antagonist than in those who did not (3.3 +/- 3.3 mIU/ml in group A versus 9.9 +/
      7.9 mIU/ml in group B, P < 0.0001, for LH; 1.3 +/- 1.1 ng/ml versus 2.1 +/- 1.9
      ng/ml for group A and B, respectively, P < 0.0001, for progesterone). CONCLUSION:
      The use of GnRH antagonist in COS/IUI cycles improves pregnancy rate, preventing
      the premature LH rise and luteinization.

PMID- 17032733
TI  - S. pombe FEAR protein orthologs are not required for release of Clp1/Flp1
      phosphatase from the nucleolus during mitosis.
AB  - Cdc14 family phosphatases are highly conserved regulators of cell-cycle
      progression. Two of the best studied members of this family are budding yeast
      Cdc14p and its fission yeast homolog Clp1p/Flp1p. The function of both
      Saccharomyces cerevisiae Cdc14p and Schizosaccharomyces pombe Clp1p/Flp1p are
      controlled in part by their regulated sequestration and release from the
      nucleolus. In the budding yeast S. cerevisiae a set of proteins collectively
      termed the FEAR network promote nucleolar and telomeric DNA segregation by
      triggering the release of the conserved Cdc14 phosphatase from the nucleolus.
      Here we show that FEAR homologs in S. pombe do not promote release of the Cdc14
      homolog Clp1p/Flp1p from the nucleolus, and that Clp1p/Flp1p is not required for
      nucleolar and telomeric DNA segregation suggesting that this aspect of Cdc14
      regulation and function may not be universally conserved.

PMID- 17032734
TI  - 14-3-3gamma affects dynamics and integrity of glial filaments by binding to
      phosphorylated GFAP.
AB  - Recent findings indicated a protective role of GFAP in ischemic brain, injured
      spinal cord, and in neurodegenerative disease. We previously demonstrated that 14
      3-3gamma, once thought to be neuronal specific, was up-regulated by ischemia in
      astrocytes and may play a specific protective role in astrocytes. Here we report
      that 14-3-3gamma associates with both soluble and filamentous GFAP in a
      phosphorylation- and cell-cycle-dependent manner in primary cultured astrocytes.
      The amount of association increases during G2/M phase due to more phosphorylated
      GFAP. Moreover, this interaction is independent of vimentin, another type III
      intermediate filament protein in astrocytes which forms glial filaments with
      GFAP. A series of domain deletion mutants and substitution mutations at
      phosphorylation sites (from serine to alanine) on GFAP demonstrated that serine 8
      in the head domain is essential for the direct association of GFAP to 14-3
      3gamma. Overexpression of 14-3-3gamma destroyed the integrity and affected the
      movement of GFAP intermediate filaments. This data demonstrates that 14-3-3gamma
      contributes to the regulation of dynamics of GFAP filaments, which may contribute
      to the stability of the cytoskeleton and the mechanisms of central nervous system
      neurodegenerative disease.

PMID- 17032735
TI  - Gliotactin and Discs large form a protein complex at the tricellular junction of
      polarized epithelial cells in Drosophila.
AB  - The tricellular junction (TCJ) forms at the convergence of pleated septate
      junctions (SJs) from three adjacent cells in polarized epithelia and is necessary
      for maintaining the transepithelial barrier. In Drosophila, the transmembrane
      protein Gliotactin was the first identified marker of the TCJ, but little is
      known about other molecular constituents. We now show that Gliotactin associates
      with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is
      essential for the formation of the TCJ and the localization of Gliotactin.
      Surprisingly, Gliotactin localization at the TCJ was independent of its PDZ
      binding motif and Gliotactin did not bind directly to Discs large. Therefore
      Gliotactin and Discs large association is through intermediary proteins at the
      TCJ. Gliotactin can associate with other septate junction proteins but this was
      detected only when Gliotactin was overexpressed and spread throughout the septate
      junction domain. Gliotactin overexpression and spread also resulted in a
      reduction of Discs large staining but not vice versa. These results suggest that
      Discs large participates in different protein interactions in the SJ and the TCJ.
      Finally this work supports a model where Gliotactin and Dlg are components of a
      larger protein complex that links the converging SJs with the TCJ to create the
      transepithelial barrier.

PMID- 17032736
TI  - BMP-2-dependent integration of adult mouse subventricular stem cells into the
      neural crest of chick and quail embryos.
AB  - Central nervous system (CNS) stem cells isolated from the subventricular zone
      (SVZ) show a remarkable differentiation potential into neural derivatives.
      Surprisingly adult SVZ cells can also be induced in vitro to differentiate into
      neural crest cell fates. This fate switch is dependent on the combination of
      fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we
      transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk
      neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2
      and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to
      the neural crest area. GFP-positive cells emigrated from the neurosphere and were
      identified in the roof plate, the dorsal neuroepithelium and among emigrating
      neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP
      2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS
      stem cells can be efficiently prepared in vitro for integration into the
      embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic
      capabilities to adult stem cells for future clinical transplantation strategies.

PMID- 17032737
TI  - The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates NFkappaB
      activation in Drosophila.
AB  - CRM1-mediated protein export is an important determinant of the nuclear
      accumulation of many gene regulators. Here, we show that the NFkappaB
      transcription factor Dorsal is a substrate of CRM1 and requires the nucleoporin
      Nup214 for its nuclear translocation upon signaling. Nup214 bound to CRM1
      directly and anchored it to the nuclear envelope. In nup214 mutants CRM1
      accumulated in the nucleus and NES-protein export was enhanced. Nup214 formed
      complexes with Nup88 and CRM1 in vivo and Nup214 protected Nup88 from degradation
      at the nuclear rim. In turn, Nup88 was sufficient for targeting the complex to
      the nuclear pores. Overexpression experiments indicated that Nup214 alone
      attracts a fraction of CRM1 to the nuclear envelope but does not interfere with
      NES-GFP export. By contrast, overexpression of the Nup214-Nup88 complex trapped
      CRM1 and Dorsal to cytoplasmic foci and inhibited protein export and immune
      response activation. We hypothesize that variation in levels of the Nup214-Nup88
      complex at the pore changes the amount of NPC-bound CRM1 and influences the
      relative strength and duration of NFkappaB signaling responses.

PMID- 17032738
TI  - RacGAP50C is sufficient to signal cleavage furrow formation during cytokinesis.
AB  - Several studies indicate that spindle microtubules determine the position of the
      cleavage plane at the end of cell division, but their exact role in triggering
      the formation and ingression of the cleavage furrow is still unclear. Here we
      show that in Drosophila depletion of either the GAP (GTPase-activating protein)
      or the kinesin-like subunit of the evolutionary conserved centralspindlin complex
      prevents furrowing without affecting the association of astral microtubules with
      the cell cortex. Moreover, time-lapse imaging indicates that astral microtubules
      serve to deliver the centralspindlin complex to the equatorial cortex just before
      furrow formation. However, when the GAP-signaling component was mislocalized
      around the entire cortex using a membrane-tethering motif, this caused ectopic
      furrowing even in the absence of its motor partner. Thus, the GAP component of
      centralspindlin is both necessary and sufficient for furrow formation and
      ingression and astral microtubules provide a route for its delivery to the
      cleavage site.

PMID- 17032739
TI  - Inhibition of RET tyrosine kinase by SU5416.
AB  - Thyroid neoplasia is frequently associated with rearranged during transfection
      (RET) proto-oncogene mutations that cause hyperactivation of RET kinase activity.
      Selective inhibition of RET-mediated signaling should lead to an efficacious
      therapy. SU5416 is a potent inhibitor of vascular endothelial cell growth factor
      receptor, c-Kit, and FLT-3 receptor tyrosine kinases presently used in clinical
      trials. We found that SU5416 inhibits RET with similar potency, both in cell-free
      assays and in cells, thus causing proliferation arrest in oncogenic RET
      transfected cells and in papillary thyroid carcinoma (PTC) cells expressing the
      RET/PTC1 oncogene, but not in RET-negative control cells. SU5416 inhibited RET
      mediated signaling through the extracellular signal regulated kinase (ERK) and
      JNK pathways. In addition, we show that a naturally occurring MEN2 mutation at
      codon 804 confers resistance to SU5416, but not to the related compound SU4984.
      We provide a possible explanation to these results by using molecular docking.
      Finally, SU5416 was also assessed against an array of 52 tyrosine and
      serine/threonine kinases.

PMID- 17032740
TI  - Corticotropin-releasing factor and its receptors in the brain of rats with
      insulin and corticosterone deficits.
AB  - The expression of genes encoding corticotropin-releasing factor (CRF) and its
      receptor type-1 (CRF1R) and type-2alpha (CRF2R) has been studied in the brain of
      rats with streptozotocin (STZ)-induced diabetes and adrenalectomy (ADX). Diabetic
      rats had a lower body weight compared to control rats. Food and water intake were
      increased in diabetic rats and decreased in ADX animals. The plasma
      corticosterone levels measured at the nadir of the circadian rhythm were
      significantly higher in diabetic rats compared to non-diabetic animals. STZ
      diabetic rats demonstrated an induction of expression of CRF mRNA in the
      magnocellular part of the paraventricular hypothalamic nucleus (PVN) and in the
      supraoptic nucleus (SON), whereas the CRF transcript in the parvocellular PVN was
      significantly lower in rats with insulin deficiency. ADX strongly triggered the
      expression of CRF mRNA in the parvocellular neurons of the PVN in both non
      diabetic and diabetic rats, and it decreased magnocellular CRF mRNA in diabetic
      animals. The expression of the CRF1R in the parvocellular and magnocellular PVN
      and in the SON was induced by diabetes and decreased after ADX. The levels of the
      CRF2R mRNA in the ventromedial hypothalamic nucleus (VMH) were significantly
      lower in diabetic rats without any noticeable effects of ADX. The present results
      suggest opposite effects of insulin and corticosterone deficiency on the
      hypophysiotropic CRF and the CRF1R mRNA contents, whereas the expression of CRF2R
      was mostly related to insulin, but not to the corticosterone status.

PMID- 17032741
TI  - A temporal switch in the insulin-signalling pathway that regulates hepatic IGF
      binding protein-1 gene expression.
AB  - Insulin regulation of hepatic gene transcription is a vital component of glucose
      homeostasis. Understanding the molecular regulationof thisprocess aids the
      searchfor the defect(s) that promotesinsulin-resistant states, such
      asdiabetesmellitus. We havepreviously shownthat the insulin regulationof hepatic
      IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins
      phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin
      (mTOR). In this report, we demonstrate that activation of the mTOR pathway,
      without activation of its upstream regulator PI 3-kinase, reduces IGFBP1
      expression. Therefore, mTOR activation is sufficient to mimic insulin regulation
      of this gene. However, longer exposure (>3 h) of cells to insulin reduces the
      importance of this pathway in insulin regulation of the gene, suggesting a
      temporal switch in signalling mechanisms linking insulin action to the IGFBP1
      gene promoter. In contrast, the activation of PI 3-kinase is required for insulin
      regulation of IGFBP1 under all conditions tested. Therefore, an mTOR-independent,
      PI 3-kinase-dependent pathway becomes more important in IGFBP1 regulation after
      long exposure to insulin. This is a novel concept in insulin regulation of gene
      expression and demonstrates the importance of temporal analysis of signalling
      processes.

PMID- 17032742
TI  - Characterization of bovine early growth response factor-1 and its gonadotropin
      dependent regulation in ovarian follicles prior to ovulation.
AB  - Early growth response factor-1 (EGR-1) is a transcription factor that is involved
      in the transactivation of several genes. The objective of this study was to
      characterize gonadotropin-dependent regulation of bovine EGR-1 in preovulatory
      follicles prior to ovulation. Bovine EGR-1 cDNA was obtained by RT-PCR, 5'- and
      3'-RACE, its open reading frame composed of 1623 bp, and its coding region
      encodes a 540-amino acid protein that displays 62-93% identity to known mammalian
      homologs. The regulation of EGR-1 mRNA was studied in bovine preovulatory
      follicles which were isolated 0-24 h post-hCG using semiquantitative RT
      PCR/Southern blot. Results revealed that the levels of EGR-1 mRNA were very low
      in follicles at 0 h, markedly increased at 6 h (P < 0.05) when compared to 0 h,
      and decreased between 12 and 24 h post-hCG. High levels of the EGR-1 mRNA were
      also observed in corpus luteum, uterus, kidney, pituitary, and spleen, moderate
      and low in other bovine tissues tested. Analyses performed on isolated
      preparations of granulosa and theca cells indicated that EGR-1 mRNA was regulated
      in both cell types, with a predominant expression in granulosa cells.
      Immunohistochemistry on sections of preovulatory follicles isolated before and
      after hCG confirmed its protein expression in granulosa cells, 24 h post-hCG.
      Studies of EGR-1 regulation in primary granulosa cells cultured with forskolin
      showed that levels of EGR-1 mRNA were low at 0 h, highly increased at 6 h post
      forskolin (P < 0.05), and declined to steady state thereafter. Immunoblotting
      confirmed forskolin-induced EGR-1 protein in cultures. Interestingly,
      overexpression of EGR-1 increased the levels of mRNA for prostaglandin (PG) G/H
      synthase-2 (PGHS-2), PG E synthase (PGES), PG E2 receptor (EP2), LH receptor (LH
      R), but not for cytochrome P450-side chain cleavage (P450scc), and cytochrome
      P450 aromatase (P450arom) in granulosa cultures. Thus, this study reports for the
      first time, a gonadotropin-dependent induction of follicular EGR-1 prior to
      ovulation in large monoovulatory species and its stimulating effect on the
      expression of genes known to be involved in prostaglandin biosynthesis pathway,
      thereby suggesting its potential involvement in the regulation of preovulatory
      events in cattle.

PMID- 17032743
TI  - PGC-1alpha regulates the isoform mRNA ratio of the alternatively spliced thyroid
      hormone receptor alpha transcript.
AB  - Transcripts derived from the thyroid hormone receptor alpha (TRalpha) gene are
      alternatively spliced resulting in a functional receptor TRalpha1 and a non-T3
      binding variant TRalpha2 that can exert a dominant negative effect on the
      transactivation functions of other TRs. There is evidence that the ratio of
      TRalpha isoform transcripts can be modulated and here, we investigate whether the
      PPARgamma co-activator alpha (PGC-1alpha) has an effect on this splicing process.
      PGC-1alpha was discovered not only as a transcriptional co-activator, but also
      has certain motifs characteristic of splicing factors. We demonstrate that PGC
      1alpha alters the ratio of endogenously expressed TRalpha isoform transcripts in
      HepG2 cells, by decreasing TRalpha1 mRNA levels twofold. This change in isoform
      ratio is accompanied by a decrease in 5'-deiodinase expression, whereas no
      differences were found in TRbeta1 expression. Deletion of the RNA-processing
      domain of PGC-1alpha abrogated the effect on the TRalpha splicing, whereas
      expression of only the RNA-processing domain favored TRalpha1 expression. PGC
      1alpha showed a similar effect on the splicing of a TRalpha minigene containing
      only the last four exons and introns of the TRalpha gene. These data suggest that
      PGC-1alpha is involved in the RNA processing of TRalpha transcripts.

PMID- 17032744
TI  - Multiple microarray platforms utilized for hepatic gene expression profiling of
      GH transgenic coho salmon with and without ration restriction.
AB  - The objectives of this study are to examine hepatic gene expression changes
      caused by GH transgenesis and enhanced growth. This is the first use of cDNA
      microarrays to study the influence of GH transgenesis on liver gene expression in
      a non-mammalian vertebrate, and the first such study using sexually immature
      animals. Three groups of coho salmon were examined: GH transgenic on full ration
      (T), GH transgenic on restricted ration (R), and control non-transgenic (C).
      Specific growth rates for weight in T were approximately eightfold higher than in
      C, and fourfold higher than in R. Differential gene expression in T, R, and C
      samples was determined using approximately 3500 and 16,000 gene microarrays, and
      R and C samples were compared on a different approximately 4000 gene microarray.
      The use of multiple microarray platforms increased the overall proportion of the
      hepatic transcriptome considered in these studies. Cross-platform comparisons
      identified genes behaving similarly between studies. For example, genes encoding
      a precerebellin-like protein and complement component C3 were downregulated in R
      relative to C (R < C) in two microarray studies, and hemoglobins alpha and beta
      were R > C in all three studies. Comparisons of informative gene lists within and
      between studies inferred causes of altered gene expression. For example, ten
      genes, including 78 kDa glucose-regulated protein, glycerol-3-phosphate
      dehydrogenase, hemoglobins alpha and beta, and a C-type lectin, were likely
      induced by GH transgenesis due to their presence in both T > C and R > C gene
      lists. Eleven genes, including hepcidin, nuclear protein p8, precerebellin-like,
      transketolase, and fatty acid-binding protein, were present in both T < C and R <
      C gene lists and were, therefore, likely suppressed by GH transgenesis. A large
      number of salmonid genes identified in these studies are involved in iron
      homeostasis, mitochondrial function, carbohydrate metabolism, cellular
      proliferation, and innate immunity. Pentose phosphate pathway genes
      phosphogluconate dehydrogenase, transaldolase, and transketolase, were
      dysregulated in GH transgenic samples relative to control samples. Changes in the
      expression of genes involved in maintaining hemoglobin levels (heme oxygenase,
      hemoglobins alpha and beta, Kruppel-like globin gene activator, hepcidin) in R
      and T fish indicate a need for additional hemoglobin in the transgenic fish,
      perhaps due to higher metabolic rate required for enhanced growth.

PMID- 17032745
TI  - Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial
      cells.
AB  - Various cofactors have been shown to regulate androgen receptor (AR)
      transactivation, but their physiological functions in the AR pathway and prostate
      tumorigenesis are undefined. Here, we found that AR cofactor (p44) translocation
      from the nucleus to the cytoplasm in prostate epithelial cells (ECs) is
      associated with prostate tumorigenesis. The forced nuclear localization of p44
      inhibited prostate cancer cell growth by G1 cell-cycle arrest. Consistently, mice
      lacking one allele of the p44 gene developed prostatic hyperplasia. Therefore,
      p44 is required for proper expression of AR-target genes to maintain the
      differentiation of prostate ECs, and p44 translocation from the nucleus into the
      cytoplasm in prostate cancer cells or loss of one allele in mouse results in
      excessive prostate EC proliferation.

PMID- 17032746
TI  - The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic
      mice.
AB  - To understand the molecular mechanisms regulating pancreatic endocrine
      development and function, pancreatic gene expression was compared between Ngn3
      deficient mice and littermate controls on embryonic days 13 and 15. Microarray
      analysis identified 504 genes with significant differences in expression. Fifty
      two of these showed at least twofold reduction in Ngn3 knockouts compared to
      controls. Many of them were previously described to be involved in endocrine
      development and function. Among the genes not previously characterized were
      Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and
      the Iroquois-type homeobox gene Irx1, the latter was selected for further
      investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1
      and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant
      embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken
      endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon
      , but not insulin- or somatostatin-producing cells in mice and chicken. These
      data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the
      regulation of alpha-cell-specific gene expression.

PMID- 17032747
TI  - Characterization of the Nurr1 ligand-binding domain co-activator interaction
      surface.
AB  - The recently solved crystal structure of the orphan nuclear receptor (NR) Nurr1
      ligand-binding domain (LBD) showed that Nurr1 lacks a cavity for ligand binding
      and a canonical NR co-activator-binding site. Computer modeling of the Nurr1 LBD
      structure identified a hydrophobic region on the surface of the Nurr1 LBD that
      was positioned on the opposite side from the classical co-activator-binding site.
      Site-directed mutagenesis demonstrated that this region is critical for the
      activity of the Nurr1 LBD. Most mutations introduced in this region reduced or
      abolished transcriptional activity of the Nurr1 LBD, but mutation at lysine
      (K577) resulted in a drastically increased activity. Moreover, the activity of
      the Nurr1 LBD was shown to correlate with a propensity for proteasome-dependent
      degradation revealing a close association between activity and Nurr1 protein
      turnover. These data provide novel insights into the mechanisms of transcription
      via the Nurr1 LBD and identify an alternative co-activator-binding surface that
      is unique to the NR4A family of NRs.

PMID- 17032748
TI  - Expression profiling of 11beta-hydroxysteroid dehydrogenase type-1 and
      glucocorticoid-target genes in subcutaneous and omental human preadipocytes.
AB  - Obesity is associated with increased morbidity and mortality from cardiovascular
      disease, diabetes and cancer. Although obesity is a multi-factorial heterogeneous
      condition, fat accumulation in visceral depots is most highly associated with
      these risks. Pathological glucocorticoid excess (i.e. in Cushing's syndrome) is a
      recognised, reversible cause of visceral fat accumulation. The aim of this study
      was to identify depot-specific glucocorticoid-target genes in adipocyte precursor
      cells (preadipocytes) using Affymetrix microarray technique. Confluent
      preadipocytes from subcutaneous (SC) and omental (OM) adipose tissue collected
      from five female patients were treated for 24 h with 100 nM cortisol (F), RNA was
      pooled and hybridised to the Affymetrix U133 microarray set. We identified 72
      upregulated and 30 downregulated genes by F in SC cells. In OM preadipocytes, 56
      genes were increased and 19 were decreased. Among the most interesting were
      transcription factors, markers of adipocyte differentiation and glucose
      metabolism, cell adhesion and growth arrest protein factors involved in G-coupled
      and Wnt signalling. The Affymetrix data have been confirmed by quantitative real
      time PCR for ten specific genes, including HSD11B1, GR, C/EBPalpha, C/EBPbeta, IL
      6, FABP4, APOD, IRS2, AGTR1 and GHR. One of the most upregulated genes in OM but
      not in SC cells was HSD11B1. The GR was similarly expressed and not regulated by
      glucocorticoids in SC and OM human preadipocytes. C/EBPalpha was expressed in SC
      preadipocytes and upregulated by F, but was below the detection level in OM
      cells. C/EBPbeta was highly expressed both in SC and in OM preadipocytes, but was
      not regulated by F. Our results provide insight into the genes involved in the
      regulation of adipocyte differentiation by cortisol, highlighting the depot
      specifically in human adipose tissue.

PMID- 17032749
TI  - Pituitary transcription factor Prop-1 stimulates porcine pituitary glycoprotein
      hormone alpha subunit gene expression.
AB  - Recently, we have reported that a Prophet of Pit-1 homeodomain factor, Prop-1, is
      a novel transcription factor for the porcine follicle-stimulating hormone beta
      subunit (FSHbeta) gene. This study subsequently aimed to examine the role of Prop
      1 in the gene expression of two other porcine gonadotropin subunits, pituitary
      glycoprotein hormone alpha subunit (alphaGSU), and luteinizing hormone beta
      subunit (LHbeta). A series of deletion mutants of the porcine alphaGSU (up to 
      1059 bp) and LHbeta (up to -1277 bp) promoters were constructed in the reporter
      vector, fused with the secreted alkaline phosphatase gene (pSEAP2-Basic).
      Transient transfection studies using GH3 cells were carried out to estimate the
      activation of the porcine alphaGSU and LHbeta promoters by Prop-1, which was
      found to activate the alphaGSU promoter of -1059/+12 bp up to 11.7-fold but not
      the LHbeta promoter. Electrophoretic mobility shift assay and DNase I
      footprinting analysis revealed that Prop-1 binds to six positions, -1038/-1026, 
      942/-928, -495/-479, -338/-326, -153/-146, and -131/-124 bp, that comprise the
      A/T cluster. Oligonucleotides of six Prop-1 binding sites were directly connected
      to the minimum promoter of alphaGSU, fused in the pSEAP2-Basic vector, followed
      by transfecting GH3 cells to determine the cis-acting activity. Finally, we
      concluded that at least five Prop-1 binding sites are the cis-acting elements for
      alphaGSU gene expression. The present results revealed a notable feature of the
      proximal region, where three Prop-1-binding sites are close to and/or overlap the
      pituitary glycoprotein hormone basal element, GATA-binding element, and
      junctional regulatory element. To our knowledge, this is the first demonstration
      of the role of Prop-1 in the regulation of alphaGSU gene expression. These
      results, taken together with our previous finding that Prop-1 is a transcription
      factor for FSHbeta gene, confirm that Prop-1 modulates the synthesis of FSH at
      the transcriptional level. On the other hand, the defects of Prop-1 are known to
      cause dwarfism and combined pituitary hormone deficiency accompanying
      hypogonadism. Accordingly, the present observations provide a novel view to
      understand the hypogonadism caused by Prop-1 defects at the molecular level
      through the regulatory mechanism of alphaGSU and FSHbeta gene expressions.

PMID- 17032750
TI  - Cloning and differential expression of estrogen receptor and aromatase genes in
      the self-fertilizing hermaphrodite and male mangrove rivulus, Kryptolebias
      marmoratus.
AB  - The mechanisms underlying sex determination and differentiation in fishes are
      labile in response to environmental parameters. Sex-specific phenotypes are
      largely regulated by sex steroids, and the inhibition or the stimulation of
      aromatase can reverse sex as well as alter secondary sexual characteristics in
      fishes. Among vertebrates, the mangrove rivulus is the only known self
      fertilizing hermaphrodite. Throughout most of its range, rivulus appear to exist
      as clonally reproducing hermaphrodites. However, outcrossing has been documented
      in Belize, where up to 25% of rivulus collected are males. The direct development
      of (primary) males occurs when embryos are incubated at 18 degrees C and
      hermaphrodites develop into secondary males when held at 28 degrees C. Given the
      importance of sex steroids, their receptors, and aromatase in sex determination
      and differentiation of fishes, we cloned, sequenced, and quantified the
      expression of estrogen receptors (ERalpha, ERbeta) and ovarian (AroA) and brain
      (AroB) aromatase genes. Hermaphrodites had increased ERalpha, ERbeta, AroA, and
      AroB gene expression in the liver, gonad, gonad, and brain respectively, compared
      to males. These data are consistent with the gene expression data reported for
      other species and are reflective of the presence of ovarian tissue in the
      hermaphrodites. Interestingly, we show the elevated expression of brain aromatase
      in the hermaphrodite brain. The role of the dimorphic expression of brain
      aromatase in the regulation of sex-specific characteristics is intriguing and
      requires further research. Because of the uniqueness of its reproductive biology,
      rivulus is an excellent model for elucidating the mechanisms regulating
      vertebrate sex determination and sexual differentiation.

PMID- 17032751
TI  - Cyclosporin A inhibits apolipoprotein AI gene expression.
AB  - Cyclosporin A (CsA), a calcineurin inhibitor, has been widely used as an
      immunosuppressant, and is known to induce hyperlipidemia and dyslipoproteinemia
      with low levels of high-density lipoprotein (HDL). Since apolipoprotein AI (apo
      AI) is a major protein component of HDL particles and reduction of apo AI results
      in low levels of HDL, we hypothesized that CsA inhibits apo AI gene expression
      contributing to its lipid effects. Therefore, we first measured the serum apo AI
      protein levels in rats with or without CsA treatment, and found that both serum
      apo AI protein and liver apo AI mRNA levels were significantly reduced in
      response to CsA treatment. In stably transfected Hep G2 cells harboring an apo AI
      474-CAT reporter gene, we found that intracellular calcium mobilization by A23187
      a calcium ionophore stimulated apo AI gene expression and the calcineurin
      inhibitors, CsA and FK605, selectively inhibited this stimulation. Therefore, we
      conclude that activation of the calcineurin pathway by intracellular calcium
      mobilization stimulates apo AI gene expression and calcineurin inhibition by CsA
      results in reduced apo AI gene expression.

PMID- 17032752
TI  - GATA factors participate in tissue-specific immune responses in Drosophila
      larvae.
AB  - Drosophila responds to infection by producing a broad range of antimicrobial
      agents in the fat body and more restricted responses in tissues such as the gut,
      trachea, and malpighian tubules. The regulation of antimicrobial genes in larval
      fat depends on linked Rel/NF-kappaB and GATA binding sites. Serpent functions as
      the major GATA transcription factor in the larval fat body. However, the
      transcriptional regulation of other tissue-specific responses is less well
      understood. Here, we present evidence that dGATAe regulates antimicrobial gene
      expression in the midgut. Regulatory regions for antimicrobial genes Diptericin
      and Metchnikowin require GATA sites for activation in the midgut, where Grain
      (dGATAc), dGATAd, and dGATAe are expressed in overlapping domains. Ectopic
      expression of dGATAe in the larval fat body, where it is normally absent, causes
      dramatic up-regulation of numerous innate immunity and gut genes, as judged by
      microarray analysis and in situ hybridization. Ectopic dGATAe also causes a host
      of symptoms reminiscent of hyperactive Toll (Toll(10b)) mutants, but without
      apparent activation of Toll signaling. Based on this evidence we propose that
      dGATAe mediates a Toll-independent immune response in the midgut, providing a
      window into the first and perhaps most ancient line of animal defense.

PMID- 17032753
TI  - FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces
      scarring, and rescues function after myocardial infarction.
AB  - Mammalian cardiomyocytes have limited proliferation potential, and acutely
      injured mammalian hearts do not regenerate adequately. Instead, injured
      myocardium develops fibrosis and scarring. Here we show that FGF1/p38 MAP kinase
      inhibitor treatment after acute myocardial injury in 8- to 10-week-old rats
      increases cardiomyocyte mitosis. At 3 months after injury, 4 weeks of FGF1/p38
      MAP kinase inhibitor therapy results in reduced scarring and wall thinning, with
      markedly improved cardiac function. In contrast, p38 MAP kinase inhibition alone
      fails to rescue heart function despite increased cardiomyocyte mitosis. FGF1
      improves angiogenesis, possibly contributing to the survival of newly generated
      cardiomyocytes. Our data indicate that FGF1 and p38 MAP kinase, proteins involved
      in cardiomyocyte proliferation and angiogenesis during development, may be
      delivered therapeutically to enhance cardiac regeneration.

PMID- 17032754
TI  - A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical
      multidrug resistance.
AB  - Hemiasterlin is a potent antimitotic peptide that interferes with microtubule
      dynamics at picomolar concentrations in cell culture. The molecule largely eludes
      P glycoprotein-mediated drug efflux, and an analog is currently being evaluated
      in clinical trials as cancer chemotherapy. From a nonclonal genetic screen in
      Caenorhabditis elegans we isolated eight independent mutants resistant to a
      synthetic hemiasterlin analog. In one recessive mutant, phb-2(ad2154), a point
      mutation in prohibitin 2 (E130K) protects worms from drug-induced injury. Data
      indicate that direct binding of hemiasterlin to prohibitin 2 is unlikely. In
      fact, C. elegans phb-2(ad2154) was also found to be resistant to numerous other
      drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to
      nocodazole and phalloidin. Thus, prohibitin 2 is implicated in a previously
      uncharacterized pathway of multidrug resistance.

PMID- 17032755
TI  - Shape and oligomerization state of the cytoplasmic domain of the phototaxis
      transducer II from Natronobacterium pharaonis.
AB  - Phototaxis allows archaea to adjust flagellar motion in response to light. In the
      photophobic response of Natronobacterium pharaonis, light-activated sensory
      rhodopsin II causes conformational changes in the transducer II protein (pHtrII),
      initiating the two-component signaling system analogous to bacterial chemotaxis.
      pHtrII's cytoplasmic domain (pHtrII-cyt) is homologous to the cytoplasmic domains
      of eubacterial chemotaxis receptors. Chemotaxis receptors require dimerization
      for activity and are in vivo-organized in large clusters. In this study we
      investigated the oligomerization and aggregation states of pHtrII-cyt by using
      chemical cross-linking, analytical gel-filtration chromatography, and small-angle
      neutron scattering. We show that pHtrII-cyt is monomeric in dilute buffers, but
      forms dimers in 4 M KCl, the physiological salt concentration for halophilic
      archaea. At high ammonium sulfate concentration, the protein forms higher-order
      aggregates. The monomeric protein has a rod-like shape, 202 A in length and 14.4
      A in diameter; upon dimerization the length increases to 248 A and the diameter
      to 18.2 A. These results suggest that under high salt concentration the shape and
      oligomerization state of pHtrII-cyt are comparable to those of chemotaxis
      receptors.

PMID- 17032756
TI  - Proton-proton Overhauser NMR spectroscopy with polypeptide chains in large
      structures.
AB  - The use of 1H-1H nuclear Overhauser effects (NOE) for structural studies of
      uniformly deuterated polypeptide chains in large structures is investigated by
      model calculations and NMR experiments. Detailed analysis of the evolution of the
      magnetization during 1H-1H NOE experiments under slow-motion conditions shows
      that the maximal 1H-1H NOE transfer is independent of the overall rotational
      correlation time, even in the presence of chemical exchange with the bulk water,
      provided that the mixing time is adjusted for the size of the structure studied.
      1H-1H NOE buildup measurements were performed for the 472-kDa complex of the 72
      kDa cochaperonin GroES with a 400-kDa single-ring variant of the chaperonin GroEL
      (SR1). These experiments demonstrate that multidimensional NOESY experiments with
      cross-correlated relaxation-enhanced polarization transfer and transverse
      relaxation-optimized spectroscopy elements can be applied to structures of
      molecular masses up to several hundred kilodaltabs, which opens new possibilities
      for studying functional interactions in large maromolecular assemblies in
      solution.

PMID- 17032757
TI  - Hot-spot mimicry of a cytokine receptor by a small molecule.
AB  - Protein-protein complexes remain enticing, but extremely challenging, targets for
      small-molecule drug discovery. In a rare example described earlier, a high
      affinity small molecule, SP4206 (Kd approximately 70 nM), was found to block
      binding of the IL-2alpha receptor (IL-2Ralpha) to IL-2 (Kd approximately 10 nM).
      Recently, the structure of the IL-2/IL-2Ralpha complex was solved [Rickert, M.,
      Wang, X., Boulanger, M. J., Goriatcheva, N., Garcia, K. C. (2005) Science
      308:1477-1480]. Using structural and functional analysis, we compare how SP4206
      mimics the 83-fold larger IL-2Ralpha in binding IL-2. The binding free energy per
      contact atom (ligand efficiency) for SP4206 is about twice that of the receptor
      because of a smaller, but overlapping, contact epitope that insinuates into
      grooves and cavities not accessed by the receptor. Despite its independent
      design, the small molecule has a similar, but more localized, charge distribution
      compared with IL-2Ralpha. Mutational studies show that SP4206 targets virtually
      the same critical "hot-spot" residues on IL-2 that drive binding of IL-2Ralpha.
      Moreover, a mutation that enhances binding to the IL-2Ralpha near these hot spots
      also enhances binding to SP4206. Although the protein and small molecule do bind
      the same hot spot, they trap very different conformations of IL-2 because of its
      flexible nature. Our studies suggest that precise structural mimics of receptors
      are not required for high-affinity binding of small molecules, and they show that
      there are multiple solutions to tight binding at shared and adaptive hot spots.

PMID- 17032758
TI  - Cell-specific expression and pathway analyses reveal alterations in trauma
      related human T cell and monocyte pathways.
AB  - Monitoring genome-wide, cell-specific responses to human disease, although
      challenging, holds great promise for the future of medicine. Patients with
      injuries severe enough to develop multiple organ dysfunction syndrome have
      multiple immune derangements, including T cell apoptosis and anergy combined with
      depressed monocyte antigen presentation. Genome-wide expression analysis of
      highly enriched circulating leukocyte subpopulations, combined with cell-specific
      pathway analyses, offers an opportunity to discover leukocyte regulatory networks
      in critically injured patients. Severe injury induced significant changes in T
      cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes)
      transcriptomes, with only 911 of these genes common to all three cell populations
      (12%). T cell-specific pathway analyses identified increased gene expression of
      several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant
      decreases in stimulatory receptors (CD28, CD4, and IL-2Ralpha). Functional
      analysis of T cells and monocytes confirmed reduced T cell proliferation and
      increased cell surface expression of negative signaling receptors paired with
      decreased monocyte costimulation ligands. Thus, genome-wide expression from
      highly enriched cell populations combined with knowledge-based pathway analyses
      leads to the identification of regulatory networks differentially expressed in
      injured patients. Importantly, application of cell separation, genome-wide
      expression, and cell-specific pathway analyses can be used to discover pathway
      alterations in human disease.

PMID- 17032759
TI  - Coordinated effects of distal mutations on environmentally coupled tunneling in
      dihydrofolate reductase.
AB  - One of the most intriguing questions in modern enzymology is whether enzyme
      dynamics evolved to enhance the catalyzed chemical transformation. In this study,
      dihydrofolate reductase, a small monomeric protein that catalyzes a single C-H-C
      transfer, is used as a model system to address this question. Experimental and
      computational studies have proposed a dynamic network that includes two residues
      remote from the active site (G121 and M42). The current study compares the nature
      of the H-transfer step of the WT enzyme, two single mutants, and their double
      mutant. The contribution of quantum mechanical tunneling and enzyme dynamics to
      the H-transfer step was examined by determining intrinsic kinetic isotope
      effects, their temperature dependence, and activation parameters. Different
      patterns of environmentally coupled tunneling were found for these four enzymes.
      The findings indicate that the naturally evolved WT dihydrofolate reductase
      requires no donor-acceptor distance fluctuations (no gating). Both single
      mutations affect the rearrangement of the system before tunneling, so some gating
      is required, but the overall nature of the environmentally coupled tunneling
      appears similar to that of the WT enzyme. The double mutation, on the other hand,
      seems to cause a major change in the nature of H transfer, leading to poor
      reorganization and substantial gating. These findings support the suggestion that
      these distal residues synergistically affect the H transfer at the active site of
      the enzyme. This observation is in accordance with the notion that these remote
      residues are part of a dynamic network that is coupled to the catalyzed
      chemistry.

PMID- 17032760
TI  - Quantification and rationalization of the higher affinity of sodium over
      potassium to protein surfaces.
AB  - For a series of different proteins, including a structural protein, enzyme,
      inhibitor, protein marker, and a charge-transfer system, we have quantified the
      higher affinity of Na+ over K+ to the protein surface by means of molecular
      dynamics simulations and conductivity measurements. Both approaches show that
      sodium binds at least twice as strongly to the protein surface than potassium
      does with this effect being present in all proteins under study. Different parts
      of the protein exterior are responsible to a varying degree for the higher
      surface affinity of sodium, with the charged carboxylic groups of aspartate and
      glutamate playing the most important role. Therefore, local ion pairing is the
      key to the surface preference of sodium over potassium, which is further
      demonstrated and quantified by simulations of glutamate and aspartate in the form
      of isolated amino acids as well as short oligopeptides. As a matter of fact, the
      effect is already present at the level of preferential pairing of the smallest
      carboxylate anions, formate or acetate, with Na+ versus K+, as shown by molecular
      dynamics and ab initio quantum chemical calculations. By quantifying and
      rationalizing the higher preference of sodium over potassium to protein surfaces,
      the present study opens a way to molecular understanding of many ion-specific
      (Hofmeister) phenomena involving protein interactions in salt solutions.

PMID- 17032762
TI  - Introduction: polymerization.

PMID- 17032761
TI  - Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism
      explaining rapidly spreading plague epizootics.
AB  - Plague is a highly virulent disease believed to have killed millions during three
      historic human pandemics. Worldwide, it remains a threat to humans and is a
      potential agent of bioterrorism. Dissemination of Yersinia pestis, the
      etiological agent of plague, by blocked fleas has been the accepted paradigm for
      flea-borne transmission. However, this mechanism, which requires a lengthy
      extrinsic incubation period before a short infectious window often followed by
      death of the flea, cannot sufficiently explain the rapid rate of spread that
      typifies plague epidemics and epizootics. Inconsistencies between the expected
      rate of spread by blocked rat fleas and that observed during the Black Death has
      even caused speculation that plague was not the cause of this medieval pandemic.
      We used the primary vector to humans in North America, Oropsylla montana, which
      rarely becomes blocked, as a model for studying alternative flea-borne
      transmission mechanisms. Our data revealed that, in contrast to the classical
      blocked flea model, O. montana is immediately infectious, transmits efficiently
      for at least 4 d postinfection (early phase) and may remain infectious for a long
      time because the fleas do not suffer block-induced mortality. These factors match
      the criteria required to drive plague epizootics as defined by recently published
      mathematical models. The scenario of efficient early-phase transmission by
      unblocked fleas described in our study calls for a paradigm shift in concepts of
      how Y. pestis is transmitted during rapidly spreading epizootics and epidemics,
      including, perhaps, the Black Death.

PMID- 17032763
TI  - Comprehensive genetic selection revealed essential bases in the peptidyl
      transferase center.
AB  - During protein synthesis, the ribosome catalyzes peptide-bond formation.
      Biochemical and structural studies revealed that conserved nucleotides in the
      peptidyl-transferase center (PTC) and its proximity may play a key role in
      peptide-bond formation; the exact mechanism involved remains unclear. To more
      precisely define the functional importance of the highly conserved residues, we
      used a systematic genetic method, which we named SSER (systematic selection of
      functional sequences by enforced replacement), that allowed us to identify
      essential nucleotides for ribosomal function from randomized rRNA libraries in
      Escherichia coli cells. These libraries were constructed by complete
      randomization of the critical regions in and around the PTC. The selected
      variants contained natural rRNA sequences from other organisms and organelles as
      well as unnatural functional sequences; hence providing insights into the
      functional roles played by these essential bases and suggesting how the universal
      catalytic mechanism of peptide-bond formation could evolve in all living
      organisms. Our results highlight essential bases and interactions, which are
      shaping the PTC architecture and guiding the motions of the tRNA terminus from
      the A to the P site, found to be crucial not only for the formation of the
      peptide bond but also for nascent chain elongation.

PMID- 17032764
TI  - Subelliptic boundary conditions for SpinC-Dirac operators, gluing, relative
      indices, and tame Fredholm pairs.
AB  - Let X be a Spin manifold with boundary, such that the Spin structure is defined
      near the boundary by an almost complex structure, which is either strictly
      pseudoconvex or pseudoconcave (and hence contact). Using generalized Szego
      projectors, we define modified partial differential-Neumann boundary conditions,
      Reo, for spinors, which lead to subelliptic Fredholm boundary value problems for
      the Spin-Dirac operator, eth(eo). To study the index of these boundary value
      problems we introduce a generalization of Fredholm pairs to the "tame" category.
      In this context, we show that the index of the graph closure of (eth(eo), Reo)
      equals the tame relative index, on the boundary, between Reo and the Calderon
      projector. Let X0 and X1 be strictly pseudoconvex, Spin manifolds, as above. Let
      phi : bX1 --> bX0, be a contact diffeomorphism, S0, S1 denote generalized Szego
      projectors on bX0, bX1, respectively, and R0(eo), R1(eo), the subelliptic
      boundary conditions they define. If X1 is the manifold X1 with its orientation
      reversed, then the glued manifold X = X0 coproduct operator(phi) X1 has a
      canonical Spin structure and Dirac operator, ethX(eo). Applying these results we
      obtain a formula for the relative index, R-Ind(S0, phi*S1), [formula: see text].
      As a special case, this formula verifies a conjecture of Atiyah and Weinstein
      [(1997) RIMS Kokyuroku 1014:1-14] for the index of the quantization of a contact
      transformation between cosphere bundles.

PMID- 17032765
TI  - Diversin regulates heart formation and gastrulation movements in development.
AB  - Canonical and noncanonical Wnt signaling regulate crucial events in the
      development of vertebrates and invertebrates. In this work we show that
      vertebrate Diversin, a potential orthologue of Drosophila Diego, controls fusion
      of heart precursors and gastrulation movements in zebrafish embryogenesis. These
      events are regulated by noncanonical Wnt signaling, which is independent of beta
      catenin. We found that Diversin directly interacts with Dishevelled and that this
      interaction is necessary and sufficient to mediate signals of the noncanonical
      Wnt pathway to downstream effectors like Rho family GTPases and Jun N-terminal
      kinase. The ankyrin repeats of Diversin are required for the interaction with
      Dishevelled, for the activation of noncanonical Wnt signaling, and for the
      biological responses. The mutation K446M in the DEP domain of vertebrate
      Dishevelled, which mimics a classical Drosophila loss of function mutation,
      prevents functional interaction with Diversin's ankyrin repeats. Diversin also
      affects planar cell polarity in Drosophila, which is controlled by the
      noncanonical Wnt signaling pathway. Our data thus demonstrate that Diversin and
      Dishevelled function together in a mutually dependent fashion in zebrafish
      gastrulation and organ formation.

PMID- 17032766
TI  - Nuclearity and cooperativity effects in binuclear catalysts and cocatalysts for
      olefin polymerization.
AB  - A series of bimetallic organo-group 4 "constrained geometry" catalysts and
      binuclear bisborane and bisborate cocatalysts have been synthesized to probe
      catalyst center-catalyst center cooperativity effects on olefin enchainment in
      homogenous olefin polymerization and copolymerization processes. Significant
      nuclearity effects are found versus mononuclear controls, and the effect can be
      correlated with metal-metal approach distances and ion pairing effects. Novel
      polymer structures can be obtained by using such binuclear catalyst/cocatalyst
      systems.

PMID- 17032768
TI  - Kinetic resolution of racemic alpha-olefins with ansa-zirconocene polymerization
      catalysts: Enantiomorphic site vs. chain end control.
AB  - Copolymerization of racemic alpha-olefins with ethylene and propylene was carried
      out in the presence of enantiopure C1-symmetric ansa metallocene, {1,2
      (SiMe2)2(eta5-C5H-3,5-(CHMe2)2)(eta5-C5H3)}ZrCl2 to probe the effect of the
      polymer chain end on enantioselection for the R- or S-alpha-olefin during the
      kinetic resolution by polymerization catalysis. Copolymerizations with ethylene
      revealed that the polymer chain end is an important factor in the
      enantioselection of the reaction and that for homopolymerization, chain end
      control generally works cooperatively with enantiomorphic site control. Results
      from propylene copolymerizations suggested that chain end control arising from a
      methyl group at the beta carbon along the main chain can drastically affect
      selectivity, but its importance as a stereo-directing element depends on the
      identity of the olefin.

PMID- 17032767
TI  - Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide
      gated channels.
AB  - Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the
      odorant sensitivity of olfactory sensory neurons by inhibiting activation of
      cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the
      intracellular face of excised patches, PIP3 has been shown to inhibit activation
      of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b
      subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels
      formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3. Using
      chimeric channels and a deletion mutant, we determined that residues 61-90 within
      the N terminus of CNGA2 are necessary for PIP3 regulation, and a biochemical
      "pulldown" assay suggests that PIP3 directly binds this region. The N terminus of
      CNGA2 contains a previously identified calcium-calmodulin (Ca2+/CaM)-binding
      domain (residues 68-81) that mediates Ca2+/CaM inhibition of homomeric CNGA2
      channels but is functionally silent in heteromeric channels. We discovered,
      however, that this region is required for PIP3 regulation of both homomeric and
      heteromeric channels. Furthermore, PIP3 occluded the action of Ca2+/CaM on both
      homomeric and heteromeric channels, in part by blocking Ca2+/CaM binding. Our
      results establish the importance of the CNGA2 N terminus for PIP3 inhibition of
      olfactory CNG channels and suggest that PIP3 inhibits channel activation by
      disrupting an autoexcitatory interaction between the N and C termini of adjacent
      subunits. By dramatically suppressing channel currents, PIP3 may generate a shift
      in odorant sensitivity that does not require prior channel activity.

PMID- 17032769
TI  - Semicrystalline thermoplastic elastomeric polyolefins: Advances through catalyst
      development and macromolecular design.
AB  - We report the design, synthesis, morphology, phase behavior, and mechanical
      properties of semicrystalline, polyolefin-based block copolymers. By using
      living, stereoselective insertion polymerization catalysts, syndiotactic
      polypropylene-block-poly(ethylene-co-propylene)-block-syndiotactic polypropylene
      and isotactic polypropylene-block-regioirregular polypropylene-block-isotactic
      polypropylene triblock copolymers were synthesized. The volume fraction and
      composition of the blocks, as well as the overall size of the macromolecules,
      were controlled by sequential synthesis of each block of the polymers. These
      triblock copolymers, with semicrystalline end-blocks and mid-segments with low
      glass-transition temperatures, show significant potential as thermoplastic
      elastomers. They have low Young's moduli, large strains at break, and better than
      90% elastic recovery at strains of 100% or less. An isotactic polypropylene-block
      regioirregular polypropylene-block-isotactic polypropylene-block-regioirregular
      polypropylene-block-isotactic polypropylene pentablock copolymer was synthesized
      that also shows exceptional elastomeric properties. Notably, microphase
      separation is not necessary in the semicrystalline isotactic polypropylenes to
      achieve good mechanical performance, unlike commercial styrenic thermoplastic
      elastomers.

PMID- 17032770
TI  - Design of stereoselective Ziegler-Natta propene polymerization catalysts.
AB  - After five decades of largely serendipitous (albeit formidable) progress,
      catalyst design in Ziegler-Natta olefin polymerization, i.e., the rational
      implementation of new active species to target predetermined polyolefin
      architectures, has ultimately become a realistic ambition, thanks to a much
      deeper fundamental understanding and major advances in the tools of computational
      chemistry. In this article, we discuss, as a case history, a unique class of
      stereorigid C2-symmetric bis(phenoxy-amine)Zr(IV) catalysts with controlled
      kinetic behavior. A large variety of polypropylene microstructures have been
      obtained with these catalysts by modulating the steric demand of one key
      substituent, without altering the nature and symmetry of the ancillary ligand
      framework, under the guidance of computer modeling. This unusual achievement is
      relevant per se and for the perspective implications in catalyst discovery.

PMID- 17032771
TI  - Study of ligand substituent effects on the rate and stereoselectivity of lactide
      polymerization using aluminum salen-type initiators.
AB  - A series of aluminum salen-type complexes [where salen is N,N'
      bis(salicylaldimine)-1,2-ethylenediamine] bearing ligands that differ in their
      steric and electronic properties have been synthesized and investigated for the
      polymerization of rac-lactide. X-ray crystal structures on key precatalysts
      reveal metal coordination geometries intermediate between trigonal bipyramidal
      and square-based pyramidal. Both the phenoxy substituents and the backbone linker
      have a significant influence over the polymerization. Electron-withdrawing groups
      attached to the phenoxy donor generally gave an increased polymerization rate,
      whereas large ortho substituents generally slowed down the polymerization. The
      vast majority of the initiators afforded polylactide with an isotactic bias; only
      one exhibited a bias toward heteroselectivity. Isoselectivity generally increases
      with increased flexibility of the backbone linker, which is presumed to be better
      able to accommodate any potential steric clashes between the propagating polymer
      chain, the inserting monomer unit, and the substituents on the phenoxy donor.

PMID- 17032772
TI  - Metallocene-catalyzed alkene polymerization and the observation of Zr-allyls.
AB  - Single-site polymerization catalysts enable exquisite control over alkene
      polymerization reactions to produce new materials with unique properties.
      Knowledge of catalyst speciation and fundamental kinetics are essential for full
      mechanistic understanding of zirconocene-catalyzed alkene polymerization.
      Currently the effect of activators on fundamental polymerization steps is not
      understood. Progress in understanding activator effects requires determination of
      fundamental kinetics for zirconocene catalysts with noncoordinating anions such
      as [B(C6F5)4]-. Kinetic NMR studies at low temperature demonstrate a very fast
      propagation rate for 1-hexene polymerization catalyzed by
      [(SBI)Zr(CH2SiMe3)][B(C6F5)4] [where SBI is rac-Me2Si(indenyl)2] with complete
      consumption of 1-hexene before the first NMR spectrum. Surprisingly, the first
      NMR spectrum reveals, aside from uninitiated catalyst, Zr-allyls as the sole
      catalyst-containing species. These Zr-allyls, which exist in two diastereomeric
      forms, have been characterized by physical and chemical methods. The mechanism of
      Zr-allyl formation was probed with a trapping experiment, leading us to favor a
      mechanism in which Zr-polymeryl undergoes beta-H transfer to metal without
      dissociation of coordinated alkene followed by sigma-bond metathesis to form H2
      and Zr-allyl. Zr-allyl species undergo slow reactions with alkene but react
      rapidly with H2 to form hydrogenation products.

PMID- 17032773
TI  - Diminishing catalyst concentration in atom transfer radical polymerization with
      reducing agents.
AB  - The concept of initiators for continuous activator regeneration (ICAR) in atom
      transfer radical polymerization (ATRP) is introduced, whereby a constant source
      of organic free radicals works to regenerate the Cu(I) activator, which is
      otherwise consumed in termination reactions when used at very low concentrations.
      With this technique, controlled synthesis of polystyrene and poly(methyl
      methacrylate) (Mw/Mn < 1.2) can be implemented with catalyst concentrations
      between 10 and 50 ppm, where its removal or recycling would be unwarranted for
      many applications. Additionally, various organic reducing agents (derivatives of
      hydrazine and phenol) are used to continuously regenerate the Cu(I) activator in
      activators regenerated by electron transfer (ARGET) ATRP. Controlled polymer
      synthesis of acrylates (Mw/Mn < 1.2) is realized with catalyst concentrations as
      low as 50 ppm. The rational selection of suitable Cu complexing ligands {tris[2
      (dimethylamino)ethyl]amine (Me6TREN) and tris[(2-pyridyl)methyl]amine (TPMA)} is
      discussed in regards to specific side reactions in each technique (i.e., complex
      dissociation, acid evolution, and reducing agent complexation). Additionally,
      mechanistic studies and kinetic modeling are used to optimize each system. The
      performance of the selected catalysts/reducing agents in homo and block
      (co)polymerizations is evaluated.

PMID- 17032774
TI  - Cyclic esters and cyclodepsipeptides derived from lactide and 2,5
      morpholinediones.
AB  - The reaction between Bu(n)Li in benzene and the solid polystyrene support PS
      C6H4CH2NH2 leads to a lithiated species that can be represented as PS
      C6H4CH2NHLi(LiBu)x, where x approximately 4, which is active in the ring-opening
      of the cyclic esters L-lactide, rac-lactide, and 2,5-morpholinediones. With
      approximately 10 eq of these monomeric six-membered rings and with heating,
      cyclic esters (MeCHC(O)O)n and [MeCHC(O)OCHRC(NH)O]n are reversibly released to
      the solution. These have been characterized by electrospray ionization MS, and
      some small rings have been separated by gel-permeation chromatography. Addition
      of NaBPh4 to a heated benzene solution containing these rings preferentially
      removes the 18-membered rings from solution. For lactide this is shown to form
      the basis for chemical amplification from a dynamic combinatorial library and
      lactide can be converted to (MeCHC(O)O)6 in >80% yield. Metallated supports
      derived from Me2Mg and Et2Zn are less reactive but do show some ability for
      lactide ring-enlarging. The 18-membered ring (R,R,R,S,S,S)- and meso
      (R,S,R,S,R,S)-(MeCHC(O)O)6 and the 24-membered ring (MeCHC(O)OCHPr(i)C(NH)O)4
      have been characterized by single-crystal x-ray diffraction studies, together
      with the complex Na[eta3-S,S,S,S,S,S-(MeCHC(O)O)6]2BPh4.

PMID- 17032775
TI  - Ansa-metallocene polymerization catalysts derived from [2+2]cycloaddition
      reactions of bis(1-methylethenyl-cyclopentadienyl)zirconium systems.
AB  - Bis(1-methylethenyl-cyclopentadienyl)zirconium dichloride (7a) was prepared by a
      fulvene route. Photolysis at 0 degrees C with Pyrex-filtered UV light resulted in
      a rapid and complete intramolecular [2+2]cycloaddition reaction to yield the
      corresponding cyclobutylene-bridged ansa-zirconocene dichloride isomer (8a). This
      is one of the rare examples of an organic functional group chemistry that leads
      to carbon-carbon coupling at the framework of an intact sensitive group 4 bent
      metallocene complex. More sterically hindered open metallocenes that bear bulky
      isopropyl or tert-butyl substituents at their Cp rings in addition to the active
      1-methylethenyl functional group undergo the photochemical ansa-metallocene ring
      closure reaction equally facile. The metallocene systems used and obtained in
      this study have served as transition metal components for the generation of
      active metallocene propene polymerization catalysts.

PMID- 17032776
TI  - Surface science of single-site heterogeneous olefin polymerization catalysts.
AB  - This article reviews the surface science of the heterogeneous olefin
      polymerization catalysts. The specific focus is on how to prepare and
      characterize stereochemically specific heterogeneous model catalysts for the
      Ziegler-Natta polymerization. Under clean, ultra-high vacuum conditions, low
      energy electron irradiation during the chemical vapor deposition of model Ziegler
      Natta catalysts can be used to create a "single-site" catalyst film with a
      surface structure that produces only isotactic polypropylene. The polymerization
      activities of the ultra-high vacuum-prepared model heterogeneous catalysts
      compare well with those of conventional Ziegler-Natta catalysts. X-ray
      photoelectron spectroscopic analyses identify the oxidation states of the Ti ions
      at the active sites. Temperature-programmed desorption distinguishes the binding
      strength of a probe molecule to the active sites that produce polypropylenes
      having different tacticities. These findings demonstrate that a surface science
      approach to the preparation and characterization of model heterogeneous catalysts
      can improve the catalyst design and provide fundamental understanding of the
      single-site olefin polymerization process.

PMID- 17032777
TI  - "Dormant" secondary metal-alkyl complexes are not omnipresent.
AB  - This theoretical study was inspired by the perpetual debate over the so-called
      "dormancy" of the active sites in propylene polymerization, i.e., a drop in their
      activity after a regioerror (2,1-insertion), which was reported to occur in many
      (although not all) catalytic systems. To explore the range of possible
      situations, we have selected two homogeneous systems of fundamentally different
      structure: an octahedral system of C2 symmetry with a tetradentate -O-N-N-O-
      ligand and a bridged indenyl catalyst. This choice was not accidental; it is in
      these two systems where the experimentalists cannot reach a consensus about
      dormancy. Our density-functional theory calculations explain why in certain
      catalytic systems both primary and secondary alkyl complexes can be equally
      reactive toward propylene polymerization, despite the intuitive concept of
      dormancy. To understand such a behavior, it was imperative to build an extensive
      model, including the counteranion and solvent effects. The discussion is also
      supplemented by our latest calculations on the classical second-generation
      Ziegler-Natta system.

PMID- 17032779
TI  - Running over rough terrain reveals limb control for intrinsic stability.
AB  - Legged animals routinely negotiate rough, unpredictable terrain with agility and
      stability that outmatches any human-built machine. Yet, we know surprisingly
      little about how animals accomplish this. Current knowledge is largely limited to
      studies of steady movement. These studies have revealed fundamental mechanisms
      used by terrestrial animals for steady locomotion. However, it is unclear whether
      these models provide an appropriate framework for the neuromuscular and
      mechanical strategies used to achieve dynamic stability over rough terrain.
      Perturbation experiments shed light on this issue, revealing the interplay
      between mechanics and neuromuscular control. We measured limb mechanics of
      helmeted guinea fowl (Numida meleagris) running over an unexpected drop in
      terrain, comparing their response to predictions of the mass-spring running
      model. Adjustment of limb contact angle explains 80% of the variation in stance
      phase limb loading following the perturbation. Surprisingly, although limb
      stiffness varies dramatically, it does not influence the response. This result
      agrees with a mass-spring model, although it differs from previous findings on
      humans running over surfaces of varying compliance. However, guinea fowl
      sometimes deviate from mass-spring dynamics through posture-dependent work
      performance of the limb, leading to substantial energy absorption following the
      perturbation. This posture-dependent actuation allows the animal to absorb energy
      and maintain desired velocity on a sudden substrate drop. Thus, posture-dependent
      work performance of the limb provides inherent velocity control over rough
      terrain. These findings highlight how simple mechanical models extend to unsteady
      conditions, providing fundamental insights into neuromuscular control of movement
      and the design of dynamically stable legged robots and prosthetic devices.

PMID- 17032780
TI  - Identification of the bovine cholesterol efflux regulatory protein ABCA1 and its
      expression in various tissues.
AB  - The ATP-binding cassette transporter A1 (ABCA1) is known to play a significant
      role in cellular export of phospholipids and cholesterol in humans. The ABCA1
      transporter might also play a crucial role in cellular cholesterol homeostasis in
      the cow or in the transfer of cholesterol into the milk, but its presence and
      tissue distribution in the bovine is unknown. Therefore, we studied the
      expression and distribution of the bovine ABCA1 transporter using quantitative
      PCR and sequenced the entire ABCA1 coding region. In addition, the proximal
      promoter was identified and screened for regulatory elements. Concordant with
      data from other mammalian species, bovine ABCA1 mRNA was expressed and detected
      in all tissues tested. The highest expression levels were detected in lung,
      esophagus, uterus, spleen, and muscle. Sequence analysis revealed that the open
      reading frame of this gene consists of 6,786 bases and encodes for a protein of
      2,261 AA with a predicted molecular weight of 254 kDa. The deduced bovine ABCA1
      protein shows the highest AA sequence homology with human (94%), mouse (93%), rat
      (92%), and chicken (85%). Analysis of the putative ABCA1 promoter region revealed
      potential transcription factor binding sites associated with ABCA1 transcription
      and lipid metabolism. This work could open new avenues for elucidating a
      potential role of ABCA1 in sterol homeostasis in the bovine organism.

PMID- 17032778
TI  - Neural correlates of epigenesis.
AB  - The effect of life stress on depression is moderated by a repeat length variation
      in the transcriptional control region of the serotonin transporter gene, which
      renders carriers of the short variant vulnerable for depression. We investigated
      the underlying neural mechanisms of these epigenetic processes in individuals
      with no history of psychopathology by using multimodal magnetic resonance-based
      imaging (functional, perfusion, and structural), genotyping, and self-reported
      life stress and rumination. Based on functional MRI and perfusion data, we found
      support for a model by which life stress interacts with the effect of serotonin
      transporter genotype on amygdala and hippocampal resting activation, two regions
      involved in depression and stress. Life stress also differentially affected, as a
      function of serotonin transporter genotype, functional connectivity of the
      amygdala and hippocampus with a wide network of other regions, as well as gray
      matter structural features, and affected individuals' level of rumination. These
      interactions may constitute a neural mechanism for epigenetic vulnerability
      toward, or protection against, depression.

PMID- 17032781
TI  - Identification of quantitative trait loci affecting corpora lutea and number of
      teats in a Meishan x Duroc F2 resource population.
AB  - Understanding of the genetic control of female reproductive performance in pigs
      would offer the opportunity to utilize natural variation and improve selective
      breeding programs through marker-assisted selection. The Chinese Meishan is one
      of the most prolific pig breeds known, farrowing 3 to 5 more viable piglets per
      litter than Western breeds. This difference in prolificacy is attributed to the
      Meishan's superior prenatal survival. Our study utilized a 3-generation resource
      population, in which the founder grandparental animals were purebred Meishan and
      Duroc pigs, in a genome scan for QTL. Grandparent, F1, and F2 animals were
      genotyped for 180 microsatellite markers. Reproductive traits, including number
      of corpora lutea (number of animals = 234), number of fetuses per animal (n =
      226), number of teats (n = 801), and total number born (n = 288), were recorded
      for F2 females. Genome-wide significance level thresholds of 1, 5, and 10% were
      calculated using a permutation approach. We identified 9 QTL for 3 traits at a
      10% genome-wise significance level. Parametric interval mapping analysis
      indicated evidence of a 1% genome-wise significant QTL for corpora lutea on SSC
      3. Nonparametric interval mapping for number of teats found 4 significant QTL on
      chromosomes SSC3 (P < 0.01), SSC7 (P < 0.01), SSC8 (P < 0.01), and SSC12 (P <
      0.05). Partial imprinting of a QTL affecting teat number (P < 0.10) was detected
      on SSC8. Using the likelihood-ratio test for a categorical trait, 2 QTL for pin
      nipples were detected on SSC2 and SSC16 (P < 0.01). Fine mapping of the QTL
      regions will be required for their application to introgression programs and gene
      cloning.

PMID- 17032782
TI  - Identification of a single nucleotide polymorphism of the insulin-like growth
      factor binding protein 2 gene and its association with growth and body
      composition traits in the chicken.
AB  - Insulin-like growth factor binding protein 2 regulates a broad spectrum of
      biological activities involved in growth, development, and differentiation. The
      current study was designed to investigate the associations of IGFBP2 gene
      polymorphisms with chicken growth and body composition traits. The Northeast
      Agricultural University Resource Population (NEAURP) was established by crossing
      broiler sires, derived from lines at Northeast Agricultural University, that were
      divergently selected for abdominal fat, with Baier layer dams, a Chinese local
      breed. The F1 birds were inter-crossed to produce an F2 population. Body weight
      and body composition traits were measured in the NEAURP. The PCR primers for the
      intron 2 region of IGFBP2 were designed based on chicken genomic sequence.
      Nucleotide polymorphisms between parental lines were detected by DNA sequencing.
      A C/T SNP in intron 2 was detected, and PCR-RFLP methods were then developed to
      genotype the F2 individuals. The results showed that the IGFBP2 SNP was
      associated with multiple traits, including BW, metatarsus length, shank length,
      femur length, shank weight, femur weight, metatarsus claw weight, and abdominal
      fat weight in the 1,028 NEAURP F2 individuals. This research suggests that IGFBP2
      or a tightly linked gene has broad effects on growth and development in the
      chicken.

PMID- 17032783
TI  - Adipocyte fatty-acid binding protein is closely associated to the porcine FAT1
      locus on chromosome 4.
AB  - We identified 22 polymorphisms in the adipocyte fatty-acid binding protein
      (FABP4) gene, a strong positional candidate gene for the FAT1 locus in porcine
      chromosome 4. The most informative polymorphism, an insertion/deletion in intron
      1, together with a single nucleotide polymorphism in intron 3, was genotyped in a
      cross between Iberian and Landrace pigs. After performing QTL, single marker, and
      haplotype analyses, we showed that there were at least 2 quantitative trait genes
      in the FAT1 region and that the FABP4 polymorphism was tightly associated to
      fatness. A comparison of allelic frequencies in a panel of pig breeds suggested
      that the Del2634C polymorphism was under indirect selection. We also showed that
      FABP4 is tightly associated to fatness but not growth. Furthermore, a haplotype
      analysis suggests that there is genetic heterogeneity at the FAT1 locus within
      the Landrace breed.

PMID- 17032784
TI  - Analysis of longevity and exterior traits on Large White sows in Switzerland.
AB  - Records of length of productive life, from first farrowing to culling, of 16,464
      Large White purebred sows from SUISAG were studied using survival analysis. The
      major aims of the study were to model the risk of culling within parity and to
      assess the influence of exterior traits, such as the number of teats or feet and
      leg scores, on culling. Culling was concentrated at the first day after each
      farrowing or at the first day after weaning. Weaning itself was mostly between 21
      and 49 d after farrowing, with an average weaning age of 35 d. Because of the
      definition of culling date used, there was practically no risk of culling from
      these periods. The culling rates at different periods suggested a modeling of the
      baseline hazard function within parity instead of over the entire productive life
      of the animals. A piecewise Weibull function and a simple graphical method to
      validate its adequacy were proposed for sow longevity analysis. The risk of
      culling increased with older parities (P < 0.001) and with decreasing litter size
      at weaning (P < 0.001). The exterior traits analyzed (number of teats, and feet
      and leg scores, on a scale from 1 to 7) had a moderate effect on the risk of
      culling compared with other factors but were still influential on survival,
      productive life expectancy, and annual replacement rate. Sows with less than 13
      good teats had 1.35 times greater risk of being culled than sows with more good
      teats (P < 0.05). Sows with an X-O rear leg score of 2 had 1.4 times greater risk
      of being culled than sows with an intermediate score of 4 (P < 0.05). Sows at the
      optimum score of 4 for the size of inner claws of the rear leg had 0.83 times
      less risk of being culled (P < 0.01) than sows with scores of 2 and 3.
      Furthermore, when a phenotypic index for feet and legs was used to group these
      variables, the effect was highly significant (P < 0.001). Therefore, a means to
      improve longevity is through phenotypic selection of replacement gilts based on
      exterior traits: gilts with 13 or less good teats or with extreme feet and leg
      scores should be culled. From a genetic point of view, sows with the best value
      in the current index for exterior traits had a lower risk of culling (P < 0.01),
      and therefore, it is possible to obtain a response for sow longevity via indirect
      selection for exterior traits. From 1999 to 2003, the trend has been to eliminate
      extreme animals on exterior traits. This may partly explain the improvement of
      sow length of productive life longevity from 560 d in 2000 to nearly 710 d in
      2003 observed in the data set.

PMID- 17032785
TI  - Genetic effects on preweaning weight gain of Nelore-Hereford calves according to
      different models and estimation methods.
AB  - Additive and nonadditive genetic effects on preweaning weight gain (PWG) of a
      commercial crossbred population were estimated using different genetic models and
      estimation methods. The data set consisted of 103,445 records on purebred and
      crossbred Nelore-Hereford calves raised under pasture conditions on farms located
      in south, southeast, and middle west Brazilian regions. In addition to breed
      additive and dominance effects, the models including different epistasis
      covariables were tested. Models considering joint additive and environment
      (latitude) by genetic effects interactions were also applied. In a first step,
      analyses were carried out under animal models. In a second step, preadjusted
      records were analyzed using ordinary least squares (OLS) and ridge regression
      (RR). The results reinforced evidence that breed additive and dominance effects
      are not sufficient to explain the observed variability in preweaning traits of
      Bos taurus x Bos indicus calves, and that genotype x environment interaction
      plays an important role in the evaluation of crossbred calves. Data were ill
      conditioned to estimate the effects of genotype x environment interactions.
      Models including these effects presented multicolinearity problems. In this case,
      RR seemed to be a powerful tool for obtaining more plausible and stable
      estimates. Estimated prediction error variances and variance inflation factors
      were drastically reduced, and many effects that were not significant under
      ordinary least squares became significant under RR. Predictions of PWG based on
      RR estimates were more acceptable from a biological perspective. In temperate and
      subtropical regions, calves with intermediate genetic compositions (close to 1/2
      Nelore) exhibited greater predicted PWG. In the tropics, predicted PWG increased
      linearly as genotype got closer to Nelore.

PMID- 17032786
TI  - A structural equation model for describing relationships between somatic cell
      score and milk yield in dairy goats.
AB  - The relationship between milk yield and somatic cell score (log-transformed
      somatic cell count) in dairy goats may involve complex pathways with recursive or
      simultaneous effects. Structural equation models were fitted to longitudinal data
      on milk yield and on somatic cell scores. Data consisted of 4 repeated records of
      milk production and of somatic cell score from left and right halves of the udder
      in each of 47 dairy goats; infection status of each of the halves at each test
      day was also available. Results strongly suggest the existence of a within-half,
      first-order autoregressive process and of simultaneity of effects between somatic
      cell scores from the left and right halves of the udder. This indicates that the
      immune response to an infection is not restricted to the half of the udder in
      which the infection takes place and that it tends to propagate over time. The
      existence of a negative effect of somatic cell score on milk yield was also
      supported by the results; however, evidence in favor of an effect in the opposite
      direction, a dilution effect, was not strong.

PMID- 17032787
TI  - Enhanced skeletal growth of sheep heterozygous for an inactivated fibroblast
      growth factor receptor 3.
AB  - Normal fibroblast growth factor receptor 3 (FGFR3) acts as a negative bone growth
      regulator by restricting chondrocyte proliferation and endochondral bone
      elongation. In sheep, a heritable mutation that inactivates FGFR3 produces
      skeletal overgrowth when homozygous, this condition is commonly referred to as
      spider lamb syndrome (SLS). We hypothesized that sheep heterozygous for the
      inactivated FGFR3 mutation (FGFR3(SLS/+)) would exhibit enhanced long bone growth
      and greater frame size; additionally, the isolated effects of increased bone
      growth would translate into greater BW and larger LM area relative to normal
      lambs at harvest. The current study investigated bone length and LM area of
      FGFR3(SLS/+) sheep at maturity and during growth. At maturity, FGFR3(SLS/+) ewes
      exhibited a larger frame size and longer bones than normal FGFR3(+/+) ewes (P <
      0.05). Similarly, FGFR3(SLS/+) lambs had greater frame sizes than normal
      FGFR3(+/+) lambs, as indicated by increased metacarpal III length and height at
      withers (P < 0.05). The FGFR3(SLS/+) lambs took longer than the normal FGFR3(+/+)
      lambs to reach the 60-kg common BW harvest end point (P < 0.05). The FGFR3(SLS/+)
      lambs showed no difference in BW, ADG, or LM area at any age compared with normal
      FGFR3(+/+) lambs (P > 0.2). A similar LM area produced in the context of a
      greater frame size and skeletal length produces a greater muscle volume, thereby
      potentially increasing meat yield. The results of this study suggest that
      FGFR3(SLS/+) animals exhibit a relaxation of the normal inhibition of chondrocyte
      proliferation, resulting in an increase in the overall frame size. The sheep
      industry could utilize the naturally occurring genetic mutation in FGFR3 to
      potentially increase meat yields with enhanced skeletal growth as an alternative
      to exogenous growth promotants.

PMID- 17032788
TI  - Melengestrol acetate alters muscle cell proliferation in heifers and steers.
AB  - In vitro experiments were performed to investigate the effects of melengestrol
      acetate (MGA) or progesterone (P4) on bovine muscle satellite cells and C2C12
      myoblasts. Addition of MGA at physiological and supraphysiological concentrations
      resulted in a dose-dependent decrease (P < 0.05) in DNA synthesis as measured by
      [3H]-thymidine incorporation (TI). Similarly, P4 addition (0.01 nM) reduced (P <
      0.05) TI. Addition of MGA (10 nM) increased (P < 0.05) IGF-I mRNA abundance but
      did not affect myogenin mRNA. Progesterone addition (10 nM) increased myogenin
      mRNA abundance (P < 0.05). In C2C12 cultures, P4 addition resulted in a dose
      dependent decrease in TI. The antiprogestin RU486, in combination with MGA or P4,
      also resulted in reduced (P < 0.05) TI. Treatment with RU486 alone had a negative
      effect (P < 0.05) on TI that was similar to the progestins. Treatment of C2C12
      myoblasts with MGA (100 nM) resulted in an increase (P < 0.05) in myogenin mRNA.
      These studies suggest that progestins may reduce satellite cell proliferation,
      ultimately affecting carcass composition.

PMID- 17032789
TI  - Growth- and breed-related changes of muscle bundle structure in cattle.
AB  - The objective of this study was to investigate the changes in muscle fiber
      bundles of cattle of different breeds during growth. Different numbers of muscle
      fibers are surrounded by connective tissue to form bundles macroscopically
      visible as meat fibers or meat grain, a common meat quality trait. To determine
      the influence of breed and age on morphological characteristics of muscle fiber
      bundles, 4 cattle breeds with different growth impetus and muscularity were
      reared and slaughtered under experimental conditions. German Angus, a typical
      beef cattle; Galloway, a smaller beef type; Holstein Friesian, a dairy type; and
      double-muscled Belgian Blue, an extreme type for muscle growth, were used.
      Between 5 and 15 bulls of each breed were slaughtered at 2, 4, 6, 12, or 24 mo of
      age, and slices of semitendinosus muscle were removed. Muscle structure
      characteristics were determined by computerized image analysis. During growth,
      the muscle cross-sectional area enlarged (P < 0.001) about 5-fold in double
      muscled Belgian Blue bulls and about 4-fold in the other breeds. This was a
      result of the enlargement (P < 0.001) of primary bundles and muscle fibers. The
      bundle size was similar (P > or = 0.15) in bulls of German Angus and Galloway in
      all age groups and was doubled (P < 0.001) in double-muscled Belgian Blue animals
      from 4 mo of age on. The Holstein Friesian bulls had the smallest (P < 0.001)
      muscle fiber bundles at 24 mo of age. The number of muscle fibers per bundle and
      the number of bundles per muscle remained nearly constant (P > 0.05) during
      growth. This supports the existing view that the structure of the muscle is
      already fixed in prenatal life. The double-muscled Belgian Blue bulls showed a
      more than 2.5-fold greater (P < 0.001) number of muscle fibers per primary bundle
      compared with the other breeds investigated. The larger muscle fiber bundles led
      to a smaller amount of connective tissue per muscle area in double-muscled
      cattle. The coarser grain of meat in double-muscled Belgian Blue bulls and in
      older animals was not related to greater shear force values.

PMID- 17032790
TI  - Effects of level of feed intake on pancreatic exocrine secretions during the
      early postweaning period in piglets.
AB  - The objective of this study was to determine the influence of the level of feed
      intake and a 2-d feed restriction period on the postweaning adaptation of
      pancreatic exocrine secretions. At 33 d of age, 18 piglets fitted with 2
      permanent catheters (for pancreatic juice collection and reintroduction) were
      weaned and allocated to 1 of the following 2 dietary treatments for 5 d:
      restricted feed allocation (restricted) or gradually increasing feed allocation
      (control). Pancreatic juice was collected daily during both basal and prandial
      periods. The basal period was defined as the period from 1400 to 1700 h (i.e., 5
      to 8 h after the morning meal), whereas the prandial period was defined as the
      period from 30 min before to 60 min after the morning meal (given at 0900).
      Digestive enzyme activities and antibacterial activity were determined.
      Pancreatic protein secretion was 44% less (P < 0.05) in restricted piglets than
      in control piglets during the basal period. Trypsin secretion was affected by
      feed-restriction of piglets. The meal did not affect protein and trypsin
      secretions in restricted piglets, whereas at d 3 postweaning, protein and trypsin
      secretions and trypsin specific activity in control piglets were 9-, 105-, and 25
      fold greater (P < 0.001) during the first 30 min after the meal than before the
      meal. Lipase and amylase secretions were not affected by variations in feed
      intake. The secretion of antibacterial activity in restricted piglets was greater
      (P < 0.05) than that of control piglets only at d 5. The extended feed
      restriction period increased the basal secretion of antibacterial activity (P =
      0.09) and postprandial secretion of amylase (P = 0.05). In conclusion, a low
      level of feed intake during the early postweaning period decreased pancreatic
      protein and trypsin secretions, whereas a 2-d feed restriction period enhanced
      secretions of amylase and antibacterial activity. In addition, our results
      indicate that during periods of dietary adaptation, such as at weaning,
      measurements of enzyme activities in the tissue do not accurately reflect the
      enzyme secretion.

PMID- 17032792
TI  - Gene expression of myostatin during development and regeneration of skeletal
      muscle in Japanese Black Cattle.
AB  - Myostatin is a specific negative regulator of skeletal muscle growth and is
      regarded as one of the most important factors for myogenesis. The aim of the
      current study was to analyze the developmental change in the gene expression of
      myostatin and an adipogenic transcription factor (peroxisome proliferator
      activated receptor lambda2) in the semitendinosus muscle of Japanese Black Cattle
      throughout the whole life cycle. An additional aim was to compare the temporal
      expression patterns of myostatin and relevant myogenic regulatory factors (MRF)
      mRNA during muscle regeneration after frostbite injury at 16 mo of age. The
      developmental pattern of myostatin gene expression exhibited 2 peaks: the
      greatest expression occurred in utero (P <0.05) and the second greatest occurred
      at 16 mo of age (P <0.05). The greatest level of peroxisome proliferator
      activated receptor lambda2 expression was observed at 16 mo of age (P <0.05),
      which paralleled myostatin expression. During frostbite-induced muscle
      regeneration, gene expression for myostatin and 4 MRF; i.e., Myf5, MyoD, myogenin
      and MRF4, showed contrasting responses. Myostatin mRNA dramatically declined by
      68.1 and 82.6% at 3 and 5 d after injury (P <0.05), respectively, which
      paralleled its protein expression, and was restored at 10 d. In contrast, the
      expressions of all 4 MRF mRNA were low initially but increased by 5 d after
      injury (P <0.05) and then remained constant or decreased slightly. These results
      suggest that myostatin may play a role in muscle marbling in the fattening period
      by decreasing myogenesis and increasing adipogenesis, and that the interaction
      between myostatin and MRF genes may take place at an early stage of skeletal
      muscle regeneration.

PMID- 17032791
TI  - Effect of anabolic agents on calpastatin promoters in porcine skeletal muscle and
      their responsiveness to cyclic adenosine monophosphate- and calcium-related
      stimuli.
AB  - The calpain proteinases and their specific inhibitor calpastatin have been
      proposed to influence both the rates of myofibrillar protein turnover in vivo and
      meat tenderization postmortem. Elevated calpastatin concentrations in particular
      are associated with certain forms of hypertrophic growth and meat toughness. In
      the 5'region of the porcine calpastatin gene, there are 3 calpastatin promoters
      upstream of exons 1xa, 1xb, and 1u, respectively, each of which contain
      transcription factor-binding motifs, suggesting sensitivity to a variety of
      growth-promoting stimuli. This study examined the effect of the beta-adrenergic
      agonist clenbuterol and porcine ST (pST) treatment on calpastatin promoter usage
      in porcine LM in vivo using real-time PCR and also the responsiveness of
      transfected calpastatin promoter sequences to cyclic adenosine monophosphate
      (cAMP) and calcium (Ca2+)-related stimuli in reporter gene systems in cell
      studies. The effect of clenbuterol and pST on potential signaling pathways in
      vivo was also assessed by monitoring protein phosphatase 2B (calcineurin),
      NFATc3, calpain 3, IkappaB alpha, and NFkappaB by quantitative immunoblotting.
      Total calpastatin mRNA was increased by 52% (P < 0.05) after treatment with
      clenbuterol for 1 d and reduced by 35% (P < 0.01) after pST treatment for 7 d.
      Whereas clenbuterol had no significant differential effects on individual mRNA
      transcripts (types 1 to 3) derived from the 3 upstream promoters, pST
      significantly reduced all of these by 51, 39, and 40% (P < 0.001, 0.05, and
      0.05), respectively. Promoter activity was increased in rat L6G8 cells
      transfected with a construct derived from exon 1u after treatment with dibutyryl
      cAMP (68%, P < 0.05) or forskolin (43%, P < 0.05), whereas 1xa activity was
      reduced by both of these agents (47 and 33%, respectively, P < 0.05). Treatment
      of cells with the calcium ionophore calcimycin reduced the activity of the 1u
      promoter by 40% (P < 0.01), with no effect on the other promoter constructs.
      Cyclosporin A had no effect on any promoter construct. The only signaling pathway
      component to be significantly altered by the in vivo treatments was calcineurin,
      which was decreased by 24% (P < 0.05) in clenbuterol-treated animals. In
      conclusion, 2 types of growth promoter in pigs had contrasting effects on
      calpastatin expression in LM. Transfected calpastatin promoters were
      differentially sensitive to cAMP- and Ca2+-related stimuli, in agreement with the
      proposed mode of action of the 2 growth promoters.

PMID- 17032793
TI  - Immunization of pigs against chicken gonadotropin-releasing hormone-II and
      lamprey gonadotropin-releasing hormone-III: effects on gonadotropin secretion and
      testicular function.
AB  - The objective of this experiment was to evaluate the effects of active
      immunization against 2 GnRH isoforms on gonadotropin secretion and testicular
      function in pigs. Synthetic chicken (c) GnRH-II and lamprey (l) GnRH-III
      peptides, with the common pGlu-His-Trp-Ser sequence at the N-terminal omitted,
      were conjugated to BSA. Forty-eight male piglets were randomly assigned to 1 of 4
      treatments. Pigs on treatment 1 were actively immunized against cGnRH-II, whereas
      pigs on treatment 2 were actively immunized against lGnRH-III. Control pigs on
      treatment 3 were actively immunized against the carrier protein (BSA), and pigs
      on treatment 4 were castrated and actively immunized against BSA. The BSA
      conjugate was emulsified in Freund's Incomplete Adjuvant and
      diethylaminoethyldextran. Primary immunization was given at 13 wk of age (WOA)
      with booster immunizations given at 16 and 19 WOA. Body weight and plasma samples
      were collected weekly beginning at 11 WOA. Treatments did not affect BW during
      the experimental period. Antibody titers were increased in animals immunized
      against cGnRH-II and lGnRH-III (P < 0.001). Cross-reactivity of the antibodies to
      mammalian GnRH or between cGnRH-II and lGnRH-III was minimal. Concentrations of
      testosterone were maximal in control boars (treatment 3) and minimal in control
      barrows (treatment 4) and immunized pigs (treatment x week; P < 0.01). Immunized
      animals had concentrations of LH (P < 0.001) and FSH (treatment x week; P < 0.03)
      that were less than control barrows and similar to control boars. At the end of
      the experiment, intact (noncastrated) pigs were exsanguinated. Testes were
      removed immediately; Leydig cells were isolated and treated with 0, 1, or 10
      ng/mL of LH. There was an LH x GnRH treatment effect on testosterone
      concentrations (P < 0.03), indicating that Leydig cells were sensitive to the
      immunization protocol and doses of LH. Taken together, these data suggest that
      immunization against GnRH isoforms decreased gonadotropin secretion compared with
      control barrows. Additionally, immunization against cGnRH-II and lGnRH-III
      reduced the ability of Leydig cells to respond to LH challenges.

PMID- 17032795
TI  - Muscle growth and plasma concentrations of amino acids, insulin-like growth
      factor-I, and insulin in growing pigs fed reduced-protein diets.
AB  - Twenty barrows were used to determine if partial replacement of protein-bound AA
      with crystalline AA (CAA) reduces AA use for muscle tissue and whole-body growth.
      Barrows (44.2 +/- 1.3 kg of BW) were assigned to 4 diets in a randomized complete
      block design. Diets consisted of 16.1% CP with no CAA, and 12.8, 10.1, and 7.8%
      CP containing CAA. As the CP concentration decreased, CAA were gradually
      increased to meet requirements on a true ileal digestibility basis. Barrows were
      weighed on d 0 and 13. Blood samples were collected before the morning feeding on
      d 0, 6, and 12 (prefeeding), and 2 h after the morning feeding on d 13
      (postfeeding). Pigs were euthanized on d 13, and liver and right LM were removed
      and weighed. The reduction in the dietary CP concentration linearly decreased (P
      < 0.01) ADG, G:F, LM weight, and the CP content of LM. Reducing the CP
      concentration decreased pre- and postfeeding plasma concentrations of IGF-I
      (linear, P < 0.01) and insulin (linear, P < 0.10). The reduction in the dietary
      CP concentration increased prefeeding plasma concentrations of Ala, Gln, Gly, and
      total AA but decreased Arg, Asn, His, Ile, Phe, Trp, and Tyr (linear, P < 0.05).
      Plasma concentration of total indispensable AA decreased initially and increased
      thereafter as the dietary CP concentration decreased from 16.1 to 7.8%
      (quadratic, P < 0.01). The reduction in the dietary CP concentration increased
      postfeeding plasma concentrations of Ala, Lys, Met (linear, P < 0.01), and Gly
      (linear, P = 0.073) and decreased Asn, Ser, Tyr, Arg, His, and Leu (linear, P <
      0.05). Plasma concentrations of Ile, Phe, Thr, Trp, and Val decreased initially
      and increased thereafter as the dietary CP concentration decreased from 16.1 to
      7.8% (quadratic, P < 0.05). In muscle tissue, concentrations of free Ala, Asp,
      Glu, Gln, Gly, and Lys increased (linear, P < 0.05) as the dietary CP
      concentration decreased. Concentrations of free His, Ile, Phe, Thr, Trp, and Val
      in muscle tissue decreased initially and increased thereafter as the dietary CP
      concentration decreased from 16.1 to 7.8% (quadratic, P < 0.05). In summary, the
      reduction in the dietary protein-bound AA decreased whole-body and LM growth,
      altered the free AA pool profile in muscle tissue, and decreased plasma insulin
      and IGF-I. As the replacement of protein-bound AA with CAA increased, 1) free Ala
      and Gln in muscle tissue increased, indicating an increase of muscle tissue
      protein breakdown; and 2) utilization of indispensable AA in muscle tissue
      decreased.

PMID- 17032794
TI  - Synchronization of estrus and artificial insemination in replacement beef heifers
      using gonadotropin-releasing hormone, prostaglandin F2alpha, and progesterone.
AB  - We evaluated whether a fixed-time AI (TAI) protocol could yield pregnancy rates
      similar to a protocol requiring detection of estrus, or detection of estrus and
      AI plus a clean-up TAI for heifers not detected in estrus, and whether adding an
      injection of GnRH at controlled internal drug release (CIDR) insertion would
      enhance fertility in CIDR-based protocols. Estrus in 2,075 replacement beef
      heifers at 12 locations was synchronized, and AI was preceded by 1 of 4
      treatments arranged as a 2 x 2 factorial design: 1) Estrus detection + TAI (ETAI)
      (n = 516): CIDR for 7 d plus 25 mg of prostaglandin F2alpha (PG) at CIDR insert
      removal, followed by detection of estrus for 72 h and AI for 84 h after PG
      (heifers not detected in estrus by 84 h received 100 microg of GnRH and TAI); 2)
      G+ETAI (n = 503): ETAI plus 100 microg GnRH at CIDR insertion; 3) Fixed-time AI
      (FTAI) (n = 525): CIDR for 7 d plus 25 mg of PG at CIDR removal, followed in 60 h
      by a second injection of GnRH and TAI; 4) G+FTAI (n = 531): FTAI plus 100 microg
      of GnRH at CIDR insertion. Blood samples were collected (d -17 and -7, relative
      to PG) to determine ovarian status. For heifers in ETAI and G+ETAI treatments, a
      minimum of twice daily observations for estrus began on d 0 and continued for at
      least 72 h. Inseminations were performed according to the a.m.-p.m. rule.
      Pregnancy was diagnosed by transrectal ultrasonography. The percentage of heifers
      exhibiting ovarian cyclic activity at the initiation of treatments was 89%.
      Pregnancy rates among locations across treatments ranged from 38 to 74%.
      Pregnancy rates were 54.7, 57.5, 49.3, and 53.1% for ETAI, G+ETAI, FTAI, and
      G+FTAI treatments, respectively. Although pregnancy rates were similar among
      treatments, a tendency (P = 0.065) occurred for pregnancy rates in the G+ETAI
      treatment to be greater than in the FTAI treatment. We concluded that the G+FTAI
      protocol yielded pregnancy rates similar to protocols that combine estrus
      detection and TAI. Further, the G+FTAI protocol produced the most consistent
      pregnancy rates among locations and eliminated the necessity for detection of
      estrus when inseminating replacement beef heifers.

PMID- 17032796
TI  - Impact of corn vitreousness and processing on site and extent of digestion by
      feedlot cattle.
AB  - Eight cannulated Holstein steers (average BW: 251 kg) were used in 2 simultaneous
      4 x 4 Latin squares in a split-plot arrangement to test the effects of processing
      method [dry-rolled (DR) vs. steam-flaked (SF); main plot] and vitreousness (V, %;
      subplot) of yellow dent corn (V55, V61, V63, and V65) on site of digestion of
      diets containing 73.2% corn grain. No vitreousness x processing method
      interactions were detected for ruminal digestion, but ruminal starch digestion
      was 14.4% lower (P < 0.01) for DR than for SF corn. Interactions were detected
      between vitreousness and processing method for postruminal (P < 0.10) and total
      tract digestion (P < 0.05). With DR, vitreousness tended to decrease (linear
      effect, P < 0.10) postruminal OM and starch digestion. With SF, vitreousness did
      not affect (P > or = 0.15) postruminal digestion of OM and starch. Postruminal N
      digestion tended to decrease (linear effect, P = 0.12) as vitreousness increased.
      Postruminal digestion was greater for SF than for DR corn OM (25.7%, P < 0.05),
      starch (94.3%, P < 0.10), and N (10.7%, P < 0.01). Steam flaking increased total
      tract digestion of OM (11%, P < 0.05), starch (16%, P < 0.01), and N (8.4%, P <
      0.05) but decreased total tract ADF digestion (26.7%, P < 0.01). With DR, total
      tract starch digestion was lower for V65 (cubic effect, P < 0.10) than for the
      other hybrids. With SF, total tract starch digestion was not affected (P > or =
      0.15) by vitreousness. Fecal starch and total tract starch digestion were
      inversely related (starch digestion, % = 101 - 0.65 x fecal starch, %; r2 = 0.94,
      P < 0.01). Ruminal pH was greater for steers fed DR than for steers fed SF corn
      (6.03 vs. 5.62, P < 0.05). Steam flaking decreased (P < 0.01) the ruminal molar
      proportion of acetate (24%), acetate:propionate molar ratio (55%), estimated
      methane production (37.5%), and butyrate (11.3%, P < 0.05). There was a
      vitreousness x processing interaction (P < 0.01) for acetate:propionate. For DR,
      acetate:propionate tended to increase (linear effect; P < 0.10) with increasing
      vitreousness. With SF, acetate:propionate was greater (cubic effect, P < 0.01)
      for V65. Starch from more vitreous corn grain was less digested when corn grain
      was DR, but this adverse effect of vitreousness on digestion was negated when the
      corn grain was SF. Of the 19% advantage in energetic efficiency associated with
      flaked over rolled corn grain, about 3/4 can be attributed to increased OM
      digestibility, with the remaining 1/4 ascribed to reduced methane loss.

PMID- 17032797
TI  - Effects of phase feeding of protein on performance, blood urea nitrogen
      concentration, manure nitrogen:phosphorus ratio, and carcass characteristics of
      feedlot cattle.
AB  - Two experiments with a randomized complete block design were conducted to
      determine the effects of phase feeding of CP on performance, blood urea nitrogen
      (BUN), manure N:P ratio, and carcass characteristics of steers fed in a feedlot.
      In Exp. 1, 45 crossbred steers (initial BW = 423 +/- 3.3 kg) were individually
      fed a diet formulated to contain 13.0% CP (DM basis) for 62 d. On d 63, the
      dietary CP was maintained at 13.0% or formulated to contain 11.5 or 10.0% CP
      until slaughter. Actual CP values were 12.8, 11.8, and 9.9%, respectively.
      Reducing the CP concentration of the diet did not affect ADG of steers from d 62
      to 109 (P = 0.54) or over the 109-d feeding period (1.45, 1.50, and 1.49 kg/d for
      13.0, 11.5, and 10.0% CP, respectively; P = 0.85). No differences (P > 0.12)
      among treatments were detected for BUN concentrations on d 0, 62, or 109.
      Gain:feed, DMI, and carcass characteristics did not differ among treatments (P >
      0.10). In Exp. 2, 2 trials were conducted using 184 (initial BW = 406 +/- 2.6 kg)
      and 162 (initial BW = 342 +/- 1.9 kg) crossbred steers. Data from the 2 trials
      were pooled for statistical analysis, and trial effect was added to the
      statistical model. Steers were fed a diet formulated to contain 13.0% CP until
      reaching approximately 477 kg. When the average BW of the pen was 477 kg, diets
      were maintained at 13.0% CP or reduced to contain 11.5 or 10.0% CP. Actual CP
      values were 12.4, 11.5, and 9.3% CP for treatments 13.0, 11.5, and 10.0% CP,
      respectively. Reducing the CP content of the diet did not affect ADG after the
      diet changed (P = 0.16) or throughout the finishing period (P = 0.14).
      Immediately before slaughter, steers fed the 13.0% CP diet had greater (P <
      0.001) BUN concentrations than steers fed the 11.5 and 10.0% CP diets. Carcasses
      from cattle fed the 11.5% CP diet had greater (P = 0.02) fat thickness than the
      13.0 and 10.0% CP treatments, whereas carcasses from cattle fed 13.0% CP had
      greater (P = 0.004) marbling scores than steers fed the 11.5 or 10.0% CP diets.
      Other carcass characteristics, DMI, and G:F did not differ (P > 0.10) among
      treatments. The N:P ratio was increased with the 10.0% CP diet (P = 0.02)
      compared with the 11.5 or 13.5% CP treatments; however, manure composition did
      not differ (P > 0.10) among treatments. These results indicate that reduced CP
      concentration during the finishing period does not affect feedlot performance but
      can improve the N and P relationship in the manure.

PMID- 17032798
TI  - Increasing the amount of n-3 fatty acid in meat from young Holstein bulls through
      nutrition.
AB  - Fifty-four Holstein bulls were blocked by initial BW (301 +/- 7.4 kg) and
      randomly assigned to 6 treatments following a 3 x 2 factorial arrangement, with 3
      concentrate lipid levels (5, 8, and 11% of DM) and 2 lipid sources (whole canola
      seed and whole linseed), with the objective of evaluating the possibility of
      increasing the content of n-3 fatty acids in meat. Concentrates (mostly corn
      meal) were isonitrogenous and isocaloric. Concentrate and straw were both fed ad
      libitum. Animal BW was recorded every 2 wk, and feed consumption was recorded
      weekly. Ruminal pH and VFA concentrations were determined monthly. Bulls were
      transported to the slaughterhouse when they achieved the target slaughter weight
      of 443 kg (after 105 +/- 4 d of fattening). After slaughter, a sample of LM from
      the sixth to the eighth ribs was dissected and analyzed for intramuscular fat
      content and fatty acid profile. Dietary lipid source did not affect overall
      animal performance, rumen fermentation, or carcass quality. Rumen pH was >6.0
      despite consumption by the bulls of large amounts of concentrate. In bulls fed
      linseed, the percentage of n-3 fatty acids in LM increased linearly with lipid
      level, whereas in bulls fed canola seed it remained constant. The ratio of n-6:n
      3 fatty acids was lower (P < 0.01) in the LM of bulls fed linseed (10.0) than in
      those fed canola seed (26.0). The content of cis-9, trans-11-CLA in the LM tended
      (P = 0.06) to be greater in the bulls fed linseed than in those fed canola seed
      (62.9 vs. 49.2 mg/kg of LM, respectively). Concentration of n-3 fatty acids in
      meat of bulls fed high-concentrate diets can be enhanced by whole linseed
      supplementation without affecting animal performance, ruminal fermentation, or
      carcass quality.

PMID- 17032799
TI  - Effects of high-sugar ryegrass silage and mixtures with red clover silage on
      ruminant digestion. 1. In vitro and in vivo studies of nitrogen utilization.
AB  - Two experiments were carried out to determine the effects of feeding grass
      silages differing in their water-soluble carbohydrate content, with or without
      red clover silage, on the efficiency of nutrient use. High-sugar grass, control
      grass, and red clover were ensiled in laboratory silos for use in an in vitro
      experiment (Exp. 1). For an in vivo experiment (Exp. 2), the same forage types
      were baled and ensiled. All silages were well preserved; within experiments the
      grass silages had similar composition, except for greater (P < 0.05) water
      soluble carbohydrate concentrations in the high-sugar than the control grass
      silage. In Exp. 1, high-sugar grass, control grass, and red clover silages were
      fed alone or as mixtures (30:70, 50:50, or 70:30 on a DM basis, respectively) of
      each grass with the red clover silage to a simulated rumen culture system. There
      were no significant differences in microbial N flow or efficiency of microbial
      protein synthesis between individual forages. However, the corresponding values
      for the 70:30 ratio of high-sugar grass:red clover silage were greater (P < 0.05)
      than for the red clover silage. The value for the efficiency of N use (g of
      microbial N/g of feed N) was greater (0.86; P < 0.05) for high-sugar grass silage
      than the control grass silage. In addition, the high-sugar grass:red clover
      silage mixtures all gave greater (P < 0.05) values for the efficiency of N use
      than red clover silage alone; this difference was not achieved with the control
      grass mixture. Experiment 2 was an incomplete Latin square design conducted with
      6 Here-ford x Friesian steers (163 +/- 5.9 kg of BW) with rumen and duodenal
      cannulas fed the following 5 silage diets: high-sugar grass silage; control grass
      silage; high-sugar grass and red clover silage (50:50 DM basis); control grass
      and red clover silage (50:50 DM basis); and red clover silage. Rumen NH3-N
      concentration was lowest (P < 0.05) with the high-sugar grass silage. Microbial N
      flows to the duodenum and efficiency of microbial protein synthesis were greater
      (P < 0.05) for steers fed the high-sugar grass silage than for control grass and
      red clover silages, and mixing red clover with grass silages increased (P < 0.05)
      these values compared with red clover silage alone. In both experiments, the
      efficiency of incorporation of silage N into microbial N was more than 20%
      greater (P < 0.05) for high-sugar grass than for control grass silage. These data
      suggest that grass silage with high-sugar content provides a forage-based
      strategy for balancing N and energy supply and improving the efficiency of use of
      grass silage N in the rumen.

PMID- 17032800
TI  - Effects of high-sugar ryegrass silage and mixtures with red clover silage on
      ruminant digestion. 2. Lipids.
AB  - The experiment investigated the digestion of lipids from different forage silages
      in beef steers. Six Hereford x Friesian steers prepared with rumen and duodenal
      cannulas were given ad libitum access to a high-sugar grass silage, control grass
      silage, red clover silage, or mixtures of the red clover and each of the grass
      silages (50:50, DM basis). The experiment was conducted as an incomplete 5 x 5
      Latin square, with an additional randomly repeated sequence. Total fatty acid and
      C18:3n-3 concentrations were greater (P < 0.05) for the high-sugar grass silage
      than the control grass silage or the red clover silage. Dry matter and total
      fatty acid intake were less (P < 0.05) for steers fed the control grass silage
      than for steers fed the other diets. Duodenal flow of C18:3n-3 was greater (P <
      0.05), and flows of C18:0 and total C18:1 trans were less (P < 0.05), for the red
      clover silage compared with the 2 grass silage diets, with the mixtures
      intermediate. These results were supported by a reduction (P < 0.05) in
      biohydrogenation of C18:3n-3 for the red clover silage, with the mixtures again
      being intermediate. Flows of total branched- and odd-chain fatty acids were
      greater (P < 0.05) for the high-sugar grass silage diet, possibly as a result of
      greater microbial flow, because these fatty acids are associated with bacterial
      lipid. Duodenal flows of the chlorophyll metabolite, phytanic acid, were greater
      (P < 0.05) for animals fed the high-sugar grass silage treatments compared with
      the other treatments. These results confirm the potential for modifying the fatty
      acid composition of ruminant products by feeding red clover silage.

PMID- 17032801
TI  - Effect of dietary vitamin E supplementation and feeding period on pork quality.
AB  - Feeding increased levels of dietary vitamin E can inhibit lipid oxidation. The
      aim of this study was to investigate the effect of levels of dietary alpha
      tocopherol acetate (VE) and feeding duration on meat quality and lipid oxidation.
      Eighty-one pigs were allocated to 1 of 3 diets containing 40, 200, or 400 IU of
      VE/kg of feed, and each diet group was divided into 3 feeding periods (3, 6, or 9
      wk). Carcass characteristics and meat quality were evaluated. Oxidative stability
      of fresh and cooked pork patties and pork chops was determined after chilled or
      frozen storage. Increasing dietary concentrations of VE did not affect any growth
      performance parameter. Drip loss, however, decreased (P < 0.05) with increased
      dietary VE levels. Moreover, an increased duration of VE feeding improved (P <
      0.05) pH and drip loss. Less lipid oxidation (P < 0.05) was detected in fresh
      ground pork from pigs fed greater concentrations of VE after 4 d of storage. A
      greater (P < 0.05) resistance to oxidation in cooked ground pork was observed in
      pigs fed 200 or 400 IU of VE/kg at 2 and 6 d of storage. Fresh and cooked pork
      patty oxidation decreased (P < 0.05) linearly as feeding duration increased from
      3 to 9 wk. After 6 mo of freezer storage, lipid oxidation of pork chops from pigs
      fed 200 or 400 IU of VE/kg was lower (P < 0.05) than for pigs fed 40 IU of VE/kg.
      Likewise, lipid oxidation of pork chops of pigs fed VE for an extended period of
      time (6 wk) was lower (P < 0.05) after 9 mo of storage. Fatty acid profiles of
      neutral lipid fraction of the LM became more unsaturated (P < 0.05) with added VE
      to the feed. These results indicate an increased intake of dietary VE
      concentration, and prolonged feeding of VE can improve drip loss and reduce lipid
      oxidation in ground pork and pork chops. This study suggests that supplementation
      with 200 IU of VE/kg of feed for 6 wk before market is beneficial in improving
      lipid stability and pork quality.

PMID- 17032802
TI  - Treadmill exercise is not an effective methodology for producing the dark-cutting
      condition in young cattle.
AB  - Holstein steer calves (n = 25) were used to evaluate the effects of treadmill
      exercise (TME) on blood metabolite status and formation of dark-cutting beef.
      Calves were blocked by BW (156 +/- 33.2 kg) and assigned randomly within blocks
      to 1 of 5 TME treatments arranged in a 2 x 2 factorial design (4 or 8 km/h for a
      duration of 10 or 15 min) with a nonexercised control. Venous blood was collected
      via indwelling jugular catheters at 10, 2, and 0 min before TME and at 2-min
      intervals during exercise. Nonexercised steers were placed on the treadmill but
      stood still for 15 min. Serum cortisol levels, as well as plasma concentrations
      of glucose, lactate, and NEFA, were similar (P > 0.05) before TME. Serum cortisol
      concentrations were unaffected (P > 0.05) during the first 6 min of TME, but
      between 8 and 15 min of TME, cortisol concentrations were greater (P < 0.05) in
      steers exercised at 8 km/h than those exercised at 4 km/h or controls (speed x
      time, P < 0.001). Although TME did not affect (P > 0.05) plasma glucose levels,
      plasma lactate concentrations in steers exercised at 8 km/h increased (P < 0.05)
      sharply with the onset of the TME treatment and remained elevated compared with
      steers exercised at 4 km/h or unexercised controls (speed x time, P < 0.001).
      Exercised steers had the lowest (P < 0.05) plasma NEFA concentrations during the
      first 6 min of TME compared with unexercised steers; however, NEFA concentrations
      were similar after 10 and 12 min of TME, and by the end of TME, steers exercised
      at 8 km/h had greater (P < 0.05) NEFA levels than nonexercised controls or steers
      exercised at 4 km/h (speed x time, P < 0.001). Even though muscle glycogen levels
      and pH decreased (P < 0.001) and muscle lactate concentrations increased (P <
      0.001) with increasing time postmortem, neither treadmill speed nor TME duration
      altered postmortem LM metabolism. Consequently, there were no (P > 0.05)
      differences in the color, water-holding capacity, shear force, or incidences of
      dark-cutting carcasses associated with preslaughter TME. It is apparent that
      preslaughter TME, at the speeds and durations employed in this study, failed to
      alter antemortem or postmortem muscle metabolism and would not be a suitable
      animal model for studying the formation of the dark-cutting condition in
      ruminants.

PMID- 17032803
TI  - Effects of dietary vitamin E and fat supplementation on pork quality.
AB  - The effects of dietary vitamin E (VE, alpha-tocopherol acetate) and fat
      supplementation on growth and carcass quality characteristics, oxidative
      stability of fresh and cooked pork patty in storage, fatty acid profiles of
      muscle and adipose tissue, and VE concentrations of plasma, muscle, and adipose
      tissue were studied. Six hundred pigs were allocated to 1 of 6 diets and fed for
      63 d in a 3 x 2 factorial design. The dietary treatments included 3 fat levels
      (normal corn, high oil corn, high oil corn plus added beef tallow) and 2 levels
      of VE supplementation (40 IU/kg, normal VE supplementation; and 200 IU/kg, high
      VE supplementation). At 113 kg of BW, 54 pigs were slaughtered as a subsample to
      evaluate dietary effects on pork quality. Growth performance and meat quality
      characteristics did not differ (P > 0.05) among treatment groups. The high level
      of VE supplementation had a beneficial effect on the oxidative stability of pork
      as indicated by thiobarbituric acid reactive substance (TBARS) values. Lean
      tissue had lower (P < 0.05) TBARS in the group fed the high VE than in those fed
      the normal VE level. The TBARS values differed among storage periods (0 to 6 d)
      and also between fresh and cooked ground ham. Fat type did not significantly
      affect total saturated and unsaturated fatty acids proportions in the neutral and
      polar fraction of muscle. Adding VE acetate led to greater (P < 0.05)
      monounsaturated and total unsaturated fatty acid proportions in neutral lipids of
      muscle and adipose tissues. Increasing dietary levels of VE acetate increased the
      concentration of VE in plasma and muscle. These results indicate that dietary VE
      acetate supplementation increased (P < 0.05) lipid stability and the VE
      concentration of muscle.

PMID- 17032804
TI  - Technical note: Exit velocity as a measure of cattle temperament is repeatable
      and associated with serum concentration of cortisol in Brahman bulls.
AB  - The objectives of this study were 1) to compare temperament assessments, using
      multiple techniques and over repeated observations, to gauge temperament over the
      long-term and 2) to evaluate the relationship of the temperament appraisals with
      serum concentrations of cortisol (CS). Measures of temperament were gathered over
      3 repeated observations (60-d interval) of yearling, fall-born Brahman bulls
      (initial BW = 320 +/- 4 kg; n = 66). Temperament assessments included exit
      velocity (EV), which was the rate at which the bulls exited the squeeze chute and
      traversed a fixed distance (1.83 m); pen scores (PEN; 1 = quiet to 5 = excited),
      ascertained from animal behavior while penned in small groups (n = 5); and chute
      scores (CHUTE; 1 = quiet to 5 = excited), determined from behavioral responses to
      restraint on the weigh scale. Temperament measures obtained during the initial
      data collection (d 0) were all positively correlated (r > or = 0.35, P < 0.005)
      with one another. Additionally, PEN (r = 0.29, P < 0.05) and EV (r = 0.26, P <
      0.05) were positively correlated with CS, whereas CHUTE was not (r = 0.09, P =
      0.46). All serial EV measures were positively correlated (r > 0.31, P < 0.02).
      All PEN were positively correlated (r > 0.31, P < 0.01), whereas serial measures
      of CHUTE were not (P > 0.3). Exit velocity was positively correlated with CS
      within d 0 (r = 0.26, P = 0.04) and 120 (r = 0.44, P < 0.01). The EV data
      obtained at d 0 were transformed into a discrete variable, EV ranking (EV RANK; 1
      to 3 scale), in which 1 equated to <1 SD below the mean and 3 equated to >1 SD
      above the mean. Mean EV (P < 0.01) decreased from d 0 (2.82 +/- 0.07 m/sec) to
      120 (2.11 +/- 0.10 m/sec). Time also influenced (P < 0.01) CS; mean CS decreased
      between d 0 (14.6 +/- 0.7 ng/mL) and 120 (11.1 +/- 0.8 ng/mL). Measures of EV can
      be a valuable tool for the assessment of cattle temperament and a possible
      predictor of temperament and stress responsiveness to future animal handling
      events.

PMID- 17032805
TI  - Voluntary intake and digestibility of reed canarygrass and timothy hay fed to
      horses.
AB  - Thousands of hectares of timothy (Phleum pretense L.) grown in the Mid-Atlantic
      region are infected by cereal rust mite (Abacarus hysterix) that causes
      discoloration and curling of leaves, decreased nutritional quality, and
      substantial decreases in yield. A decline in production of timothy hay can lower
      income for hay producers and cause horse owners to search for alternative hays.
      Low alkaloid reed canarygrass (Phalaris arundinacea L.) hay has potential as an
      alternative to timothy hay because it grows well in the Mid-Atlantic region, is
      believed to have a similar nutrient quality to timothy, and is not as susceptible
      to cereal rust mite. Eleven mature, stalled Thoroughbred geldings (549 +/- 12.1
      kg) that were exercised daily were used to compare voluntary DMI and apparent
      nutrient DM digestibility of timothy and low-alkaloid Chiefton variety reed
      canarygrass hay. Horses were paired by age and BW and randomly assigned to
      timothy or reed canarygrass hay during a 14-d period to measure voluntary DMI
      followed by a 4-d period to measure apparent DM digestibility. Both hays met the
      minimum requirements for DE, CP, Ca, P, K, Fe, and Mn, but they did not meet the
      minimum requirements for Cu, Zn, and Na for horses at maintenance and averaging
      550 kg of BW. Timothy hay seemed to have a lower CP concentration (14.4%)
      compared with reed canarygrass hay (17.1%) and a more desirable Ca:P ratio at
      1.6:1 compared with 0.8:1 for reed canarygrass hay. Horses fed timothy consumed
      more hay (P <0.001) during the voluntary DMI period compared with horses fed reed
      canarygrass. Greater voluntary DMI of timothy occurred on d 1, 3, and 5 (P
      <0.05), but DMI was similar for other days. Apparent DM digestibility was greater
      in horses fed timothy hay by 9.6% compared with horses fed reed canarygrass hay
      (P <0.05). Horses fed timothy had greater DM digestibility of ADF (P = 0.001),
      NDF (P = 0.001), sugar (P = 0.05), and Ca (P = 0.001) but lower apparent DM
      digestibility of CP (P = 0.012) and crude fat (P = 0.004). Timothy hay was
      superior in voluntary DMI and apparent DM digestibility compared with low
      alkaloid reed canarygrass hay fed to horses.

PMID- 17032806
TI  - The influence of dietary field peas (Pisum sativum L.) on pig performance,
      carcass quality, and the palatability of pork.
AB  - An experiment was conducted to test the hypothesis that field peas may replace
      soybean meal in diets fed to growing and finishing pigs without negatively
      influencing pig performance, carcass quality, or pork palatability. Forty-eight
      pigs (initial average BW 22.7 +/- 1.21 kg) were allotted to 1 of 3 treatments
      with 2 pigs per pen. There were 8 replications per treatment, 4 with barrows and
      4 with gilts. The treatments were control, medium field peas, and maximum field
      peas. Pigs were fed grower diets for 35 d, early finisher diets for 35 d, and
      late finisher diets for 45 d. Pigs receiving the control treatment were fed corn
      soybean meal diets. All diets fed to pigs receiving the medium field peas
      treatment contained 36% field peas and varying amounts of corn; soybean meal was
      also included in the grower and the early finisher diets fed to pigs on this
      treatment. In contrast, no soybean meal was included in diets fed to pigs on the
      maximum field peas treatment, and field peas were included at concentrations of
      66, 48, and 36% in the grower, early finisher, and late finisher diets,
      respectively. Pig performance was monitored within each phase and for the entire
      experimental period. At the conclusion of the experiment, carcass composition,
      carcass quality, and the palatability of pork chops and pork patties were
      measured. Results showed that there were no effects of dietary treatments on
      ADFI, ADG, or G:F. Likewise, there were no differences in carcass composition
      among the treatment groups, but gilts had larger (P = 0.001) and deeper (P =
      0.003) LM, less backfat (P = 0.007), and a greater (P = 0.002) lean meat
      percentage than barrows. The pH and marbling of the LM, and the 10th rib backfat
      were not influenced by treatment, but there was a trend (P = 0.10) for more
      marbling in barrows than in gilts. The subjective color scores (P = 0.003) and
      the objective color score (P = 0.06) indicated that dietary field peas made the
      LM darker and more desirable. Pork chops from pigs fed field peas also had less
      (P = 0.02) moisture loss compared with chops from pigs fed the control diet.
      Treatment or sex did not influence palatability of pork chops or pork patties. In
      conclusion, field peas may replace all of the soybean meal in diets fed to
      growing and finishing pigs without negatively influencing pig performance,
      carcass composition, carcass quality, or pork palatability.

PMID- 17032807
TI  - Effect of timing of feeding a high-concentrate diet on growth and attainment of
      puberty in early-weaned heifers.
AB  - Precocious puberty (<300 d of age) can be successfully induced in a majority of
      heifers with early weaning and continuous feeding of a high-concentrate diet. The
      objective of this experiment was to determine the relative effects of timing of
      feeding a high-concentrate diet on age at puberty in early-weaned heifers. Sixty
      crossbred Angus and Simmental heifer calves were weaned at 112 +/- 2 d of age and
      155 +/- 3 kg of BW and were fed a receiving diet for 2 wk. Heifers were blocked
      by age and BW, and assigned randomly to receive a high-concentrate (60% corn; H)
      or control (30% corn; C) diet during phase 1 (mean age 126 to 196 d) and H or C
      during phase 2 (mean age 196 to 402 d), resulting in 4 treatments (HH, n = 15;
      HC, n = 15; CH, n = 15; and CC, n = 15). Blood samples were collected weekly
      beginning at a mean age of 175 d and assayed for progesterone concentration to
      determine age at puberty. After 56 d on the experimental diets, BW of heifers fed
      the H diet during phase 1 were greater (P < 0.05) than those of heifers fed the C
      diet (mean age of 182 d; treatment x mean age, P < 0.01). After 70 d on the new
      diets (mean age of 266 d), heifers fed the H diet during phase 2 reached heavier
      BW (P < 0.05) than heifers fed the C diet, when compared within phase 1 diet
      groups (HH > HC; CH > CC). Body weights in HC and CH treatments differed from a
      mean age of 169 through 238 d, after which BW did not differ between these
      treatments. The ADG over the entire experimental period was greatest for the HH
      treatment (1.2 +/- 0.04 kg/d; P < 0.05), followed by the HC and CH treatments
      (1.0 +/- 0.03 and 1.0 +/- 0.02 kg/d, respectively), which were not different, and
      the CC treatment gained the least (0.7 +/- 0.04 kg/d; P < 0.05). Precocious
      puberty occurred in 67, 47, 47, and 20% of heifers in the HH, HC, CH, and CC
      treatments, respectively (HH > CC; P < 0.05). Mean age at puberty for the HH and
      HC treatments (271 +/- 17 and 283 +/- 17 d of age, respectively) was earlier (P <
      0.05) than for the CC treatment (331 +/- 11 d of age). Age at puberty in the CH
      treatment (304 +/- 13 d of age) was intermediate to and not different from the
      other treatments. Heifers fed the H diet during phase 1 attained puberty earlier
      (P < 0.05) than heifers fed the C diet during phase 1. In conclusion, increasing
      dietary energy intake in early-weaned heifers, through feeding a high-concentrate
      diet from 126 to 196 d of age, decreased age at puberty regardless of the diet
      fed after 196 d of age.

PMID- 17032808
TI  - Effect of diet composition on water consumption in growing pigs.
AB  - Concerns relating to use of water resources by the livestock industry, combined
      with the rising cost of manure management, have resulted in greater interest in
      identifying ways to reduce drinking water utilization by pigs while maintaining
      animal well-being and achieving satisfactory growth performance. The objective of
      this experiment was to determine if increasing the dietary CP or mineral
      concentrations increases water intake and excretion and, conversely, if reducing
      the dietary CP content reduces water intake and excretion. Forty-eight barrows
      (34.3 +/- 4.6 kg of BW; 12/treatment) were given free access to diets containing
      a low protein (16.9% CP), high protein (20.9% CP), or excess protein (25.7% CP)
      level, or a diet with excess levels of Ca, P, Na, and Cl. Water was available to
      each pig on an ad libitum basis via dish drinkers that were determined to waste
      less than 3% of total water flow. The excess CP diet tended to increase average
      daily water intake (ADWI) and urinary excretion (P < 0.10) and increased the
      water:feed ratio (P < 0.05); lowering dietary CP did not lower water intake or
      excretion. The excess mineral diet did not increase ADWI or urinary excretion but
      did increase water excretion via the feces. Daily nutrient intake and dietary
      nutrient concentration were poor predictors of ADWI; only daily intake of N and K
      were significantly correlated with ADWI (P < 0.05), and the r-values were low
      (0.39 and 0.32, respectively). There was no relationship between ADFI and ADWI.
      The average water:feed ratio was 2.6:1. Any study of water utilization is
      complicated by behavioral as well as nutritional and physiological influences,
      and isolating physiological need from so-called luxury intake is a significant
      experimental challenge. Because the impact of dietary treatment on water
      utilization was small, we conclude that factors other than dietary protein and
      mineral concentration and daily protein and mineral intake have a relatively
      large effect on water intake and excretion. Consequently, strategies to reduce
      water intake must recognize, understand, and manage these additional behavioral
      and physiological factors. Diet composition may be a part of strategies designed
      to reduce excessive water utilization by the pig industry but may have a limited
      effect if other important factors are ignored.

PMID- 17032809
TI  - In vivo mechanical and in vitro electromagnetic side-effects of a ruminal
      transponder in cattle.
AB  - This work was undertaken to assess the long-term impacts of a ruminal
      transponder, used for electronic identification, on ruminal motility and on
      health and performance of cattle, as well as to study the electromagnetic effects
      on ruminal bacteria in vitro. A passive transponder (51.4 g, 67 x 17 mm) was
      delivered into the forestomachs of 8 calves, 32 bulls, 10 heifers, and 40 dairy
      cows. Final readability was 87.5% in calves, 96.9% in bulls, 90% in heifers, and
      100% in cows at 481, 360, 650, and 601 d, respectively, after transponder
      administration. The transponder did not affect production or reproduction of cows
      over a 2-yr period, or performance of bulls, or mortality compared with control
      animals. Chewing movements per bolus were lower (P <0.01) in treated animals than
      in controls (49.6 vs. 52.2, 51.2 vs. 63.6, and 57.0 vs. 59.7 for bulls, heifers,
      and cows, respectively). Regurgitation frequency (number of boluses/10 min)
      tended to be greater in treated cattle: 12.4 vs. 11.3 (P = 0.07), 11.3 vs. 10.6,
      and 11.3 vs. 10.7 (P = 0.08) for bulls, heifers, and cows, respectively.
      Rumination patterns of calves fitted with transponders within the first weeks of
      life were similar to controls. During the experiment, 43 treated animals (8
      calves, 29 bulls, and 6 cows) were slaughtered. Thirty transponders were
      localized in the reticulum (3 calves, 24 bulls, and 3 cows), 11 in the rumen (4
      calves, 4 bulls, and 3 cows), and 2 were not recovered (1 calf and 1 bull).
      Within the calves, 57% of the boluses were found in the rumen. In 8 reticula (2
      calves and 6 bulls) and 1 rumen (1 cow), an impression left by physical contact
      of the transponder was observed, although histological examination did not reveal
      specific lesions in the mucosa of the dystrophic areas. In strained, whole
      ruminal contents incubated in vitro, pH values were lower after 24 and 48 h (P
      <0.001) of continuous exposure to an electromagnetic field induced by the
      transponder-reading system. After 48 h of incubation, total bacterial numbers and
      NH3-N concentration were greater (P <0.001) in exposed flasks than in controls.
      These data indicate that the transponder may alter, via mechanical action, the
      reticuloruminal mucosa and rumination patterns. Furthermore, the transponder may
      increase, via its electromagnetic action, the growth rate and metabolic activity
      of ruminal bacteria.

PMID- 17032810
TI  - Meta-analysis of factors affecting carcass characteristics of feedlot steers.
AB  - A meta-analysis was conducted to assess the effects of biological type (early
      moderate or late maturity) and implant status (estrogenic, combination, or
      nonimplanted; repeats included) on HCW (kg); LM area (cm2); 12th-rib fat
      thickness (fat thickness, cm); KPH (%), and intramuscular fat (%) at harvest, to
      provide inputs to an ongoing program for modeling beef cattle growth and carcass
      quality. Forty-three publications from 1982 to 2004 with consistent intramuscular
      fat data were evaluated. Two studies were undertaken: 1) with fat thickness as a
      covariate and 2) with BW as a covariate. The intercept-slope covariance estimate
      was not statistically different from 0 for LM area (P = 0.11), KPH (P = 0.19),
      and intramuscular fat (P = 0.74) in study 1, and for LM area (P = 0.44), fat
      thickness (P = 0.11), KPH (P = 0.19), and intramuscular fat (P = 0.74) in study
      2; therefore, a reduced model without a covariance component was fitted for these
      carcass characteristics. A covariance component was fitted for HCW (P = 0.01,
      study 1 and P = 0.05, study 2) and for intramuscular fat (P = 0.05, study 2). In
      study 1, the results for maturity indicated differences between early-moderate
      and late maturity for HCW (P < 0.01) and LM area (P < 0.01) but no differences
      for KPH (P = 0.26) and intramuscular fat (P = 0.50); for implant status, an
      estrogenic or combination implant increased HCW by 2.9% (P = 0.27) or 4.8% (P <
      0.01), increased LM area by 3.2% (P = 0.23) or 6.3% (P < 0.01), decreased
      intramuscular fat by 8.1% (P < 0.01) or 5.4% (P < 0.01), respectively, and
      decreased KPH by 7.6% (P = 0.34) for estrogenic implants but increased KPH by
      1.1% (P = 0.36) for combination implants, compared with nonimplanted steers. In
      study 2, the results at 600 kg of BW for implant status (implant or nonimplant)
      indicated no differences for HCW (P = 0.63) and LM area (P = 0.73), but there
      were differences for fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular
      fat (P < 0.01); the results for maturity (early-moderate or late maturity)
      indicated no differences for HCW (P = 0.94), but there were differences for LM
      area (P < 0.01), fat thickness (P < 0.01), KPH (P < 0.01), and intramuscular fat
      (P < 0.01). The difference between early-moderate and late maturity (studies 1
      and 2) confirmed that frame size accounts for a substantial portion of the
      variation in carcass composition. Studies 1 and 2 also indicate that implant
      status had significant effects on carcass quality.

PMID- 17032811
TI  - Interindividual variability in plasma concentrations after systemic exposure of
      swine to dietary doxycycline supplied with and without paracetamol: a population
      pharmacokinetic approach.
AB  - Anorexigenic substances released during infection may hinder the therapeutic
      efficacy of in-feed antibiotics. Paracetamol (acetaminophen; PARA) inhibits the
      anorexia of infection and seems to improve the clinical efficacy of doxycycline
      (DOX) against bacterial respiratory disease in swine herds. In order to verify
      whether PARA selectively stimulates intake of DOX-medicated feed in diseased
      pigs, we documented the pharmacokinetics (PK) of DOX when coadministered with
      PARA and examined the effect of in-feed PARA on the interindividual variability
      in plasma concentrations after systemic exposure to in-feed DOX in swine herds
      with respiratory disease. Systemic exposure to DOX was measured with the area
      under the curve (AUC) of its plasma concentrations over time. First, a rich
      sampling PK study of in-feed and i.v. DOX (10 mg/kg of BW) and PARA (30 and 10
      mg/kg of BW, respectively) was performed on 5 pigs. The PK profiles of in-feed
      DOX were used in mathematical simulations to determine 5 optimal sampling times
      for the farm-based population PK study. A randomized, blind, parallel PK study
      was performed in 2 herds with bacterial respiratory disease, where liquid feed
      was fortified with DOX alone (5 mg x kg of BW(-1) x meal(-1)) or combined with
      PARA (15 mg x kg of BW(-1) x meal(-1)). Medicated meals were given twice, 12 h
      apart, to group-housed growing pigs (n > 50 pigs x treatment(-1) x herd(-1),
      totaling 215 pigs). Plasma concentrations of DOX and PARA were measured with
      HPLC. At variance with our expectations, PARA decreased (P = 0.069) mean AUC of
      in-feed DOX and did not decrease its variability (P > 0.34). Mean AUC of DOX
      increased with feed intake and with initial exposure to DOX, and was greater in
      sick animals. Therefore, symptomatic PARA-induced improvement in bacterial
      respiratory disease control with DOX is more likely caused by its
      analgesic/antipyretic effects than by its orexigenic effect. Interindividual
      variation in the AUC of DOX was large in pigs given group medication, even when
      sufficient feeding space was allowed and the amount of feed offered was greater
      than their requirements. Therefore, future studies to improve the efficacy of
      group antibiotic therapy should focus on feeding behavior characteristics as well
      as biopharmaceutical properties of medicated feeds.

PMID- 17032813
TI  - Fundamental questions about genes, inactivity, and chronic diseases.
AB  - Currently our society is faced with the challenge of understanding the biological
      basis for the epidemics of obesity and many chronic diseases, including Type 2
      diabetes. Physical inactivity increases the relative risk of coronary artery
      disease by 45%, stroke by 60%, hypertension by 30%, and osteoporosis by 59%.
      Moreover, physical inactivity is cited as an actual cause of chronic disease by
      the US Centers of Disease Control. Physical activity was obligatory for survival
      for the Homo genus for hundreds of thousands of years. This review will present
      evidence that suggests that metabolic pathways selected during the evolution of
      the human genome are inevitably linked to physical activity. Furthermore, as with
      many other environmental interactions, cycles of physical activity and inactivity
      interact with genes resulting in a functional outcome appropriate for the
      environment. However, as humans are less physically active, there is a
      maladaptive response that leads to metabolic dysfunction and many chronic
      diseases. How and why these interactions occur are fundamental questions in
      biology. Finally, a perspective to future research in physical inactivity-gene
      interaction is presented. This information is necessary to provide the molecular
      evidence required to further promote the primary prevention of chronic diseases
      through physical activity, identify those molecules that will allow early disease
      detection, and provide society with the molecular information needed to counter
      the current strategy of adding physical inactivity into our lives.

PMID- 17032812
TI  - Assessment of vasoconstrictive potential of D-lysergic acid using an isolated
      bovine lateral saphenous vein bioassay.
AB  - Vasoconstriction has been associated with several symptoms of fescue toxicosis
      thought to be alkaloid induced. Lysergic acid, an ergot alkaloid, has been
      proposed as a toxic component of endophyte-infected tall fescue. The objective of
      this study was to examine the vasoconstrictive potential of D-lysergic acid using
      a bovine lateral (cranial branch) saphenous vein bioassay. Before testing
      lysergic acid, validation of the bovine lateral saphenous vein bioassay for use
      with a multimyograph apparatus was conducted using a dose-response to
      norepinephrine to evaluate the effects of limb of origin (right vs. left) and
      overnight storage on vessel contractile response. Segments (2 to 3 cm) of the
      cranial branch of the lateral saphenous vein were collected from healthy mixed
      breed cattle (n = 12 and n = 7 for the lysergic acid and norepinephrine
      experiments, respectively) at local abattoirs. Tissue was placed in modified
      Krebs-Henseleit, oxygenated buffer and kept on ice or stored at 2 to 8 degrees C
      until used. Veins were trimmed of excess fat and connective tissue, sliced into 2
      to 3-mm sections, and suspended in a myograph chamber containing 5 mL of
      oxygenated Krebs-Henseleit buffer (95% O2, 5% CO2; pH = 7.4; 37 degrees C).
      Tissue was allowed to equilibrate at 1 g of tension for 90 min before initiation
      of treatment additions. Increasing doses of norepinephrine (1 x 10(-8) to 5 x 10(
      4) M) or lysergic acid (1 x 10(-11) to 1 x 10(-4) M) were administered every 15
      min after buffer replacement. Data were normalized as a percentage of the
      contractile response induced by a reference dose of norepinephrine. Veins from
      both left and right limbs demonstrated contractions in a dose-dependent manner (P
      < 0.01) but did not differ between limbs. There were no differences in dose
      response to norepinephrine between tissue tested the day of dissection and tissue
      tested 24 h later. Exposure of vein segments to increasing concentrations of
      lysergic acid did not result in an appreciable contractile response until the
      addition of 1 x 10(-4) M lysergic acid (15.6 +/- 2.3% of the 1 x 10(-4) M
      norepinephrine response). These data indicate that only highly elevated
      concentrations of lysergic acid result in vasoconstriction. Thus, in relation to
      the symptoms associated with vasoconstriction, lysergic acid may only play a
      minor role in the manifestation of fescue toxicosis.

PMID- 17032814
TI  - Genome-wide analysis of SPAK/OSR1 binding motifs.
AB  - Based on the alignment of 12 sequences of protein motifs that interact with the
      kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative
      stress response 1), we performed genome-wide searches of the sequence
      [S/G/V]RFx[V/I]xx[V/I/T/S]xx, where x represents any amino acid. The "Mus
      musculus" search resulted in the identification of 131 mouse proteins containing
      137 SPAK/OSR1 putative binding motifs. Similar numbers were found for human,
      zebrafish, fruit fly, and worm. A little more than half of the mouse proteins
      containing SPAK/OSR1 binding domains (53%) were also identified in the human
      search, whereas approximately 17-18% of these common hits were identified in the
      zebrafish search. The mouse proteins could be divided into two broad categories:
      2/3 had an identified function, whereas 1/3 were either predicted or of unknown
      function. The known proteins were grouped as transport proteins, other membrane
      proteins, kinases, phosphatases, cytoskeletal, ribosomal, nuclear, enzymes, and
      others. Analysis of the location of the SPAK/OSR1 binding motif within the
      protein sequence revealed distribution throughout the entire length, but with
      preference to the extreme amino- or carboxyl termini for a large number of
      proteins. Analysis of the amino acid composition of the motifs revealed a
      preponderance of serine residues at positions 5, 6, 7, and 8. In summary, our new
      search found and thus confirms the 12 proteins previously shown to interact with
      the kinases and identifies 119 potential new targets for SPAK and OSR1 in the
      mouse proteome.

PMID- 17032815
TI  - Effects of temperature during rearing and crating on stress parameters and meat
      quality of broilers.
AB  - Two trials were conducted to study the effects of heat stress during rearing
      (trial 1) and crating (trial 2) on broiler stress parameters and fear, breast
      meat quality, and nutrient composition. The relationships between stress
      parameters and meat quality traits were also determined. Trial 1 consisted of 3
      temperature treatments from 3 to 7 wk: control (temperature was 22 degrees C);
      diurnal cyclic temperature (temperature was 28 degrees C from 1000 to 1700 h and
      22 degrees C from 1700 to 1000 h); and constant high temperature (34 degrees C;
      temperature was 34 degrees C). In trial 2, broilers from the control and 34
      degrees C groups in trial 1 were used. Broilers in each group were placed in
      transport cages. The 9 cages from the control group were divided into 3 groups
      and placed into 3 rooms at 15, 22, or 34 degrees C for 2 h. The 3 cages from the
      34 degrees C group were also held in the room at 34 degrees C (34-34 degrees C).
      Diurnal cyclic temperature had no effect on BW up to 5 wk of age. The effect of
      34 degrees C constant temperature on BW of broilers increased with age. Plasma
      levels of glucose and albumin increased by 34 degrees C, but no dramatic change
      in levels occurred when those broilers were crated at 34 degrees C. The
      heterophil:lymphocyte (H:L) was higher for the 34-34 degrees C broilers and the
      control broilers in the 34 degrees C room than those from the 22 and 15 degrees C
      room. Breast muscle glycogen level decreased in broilers reared under diurnal
      cyclic or high temperatures. A lower pH and higher lightness (L*) and redness
      values and redness:yellowness were found in meat for broilers from both 34
      degrees C and 34-34 degrees C groups. Higher H:L was associated with breast
      muscle pH according to first-order polynomial regression. The H:L had a
      significant effect on L* values, which were described by a second-order
      polynomial regression. Blood glucose level was positively correlated with L* and
      redness values. Duration of tonic immobility was neither influenced by rearing
      and crating temperatures nor associated with meat quality parameters.

PMID- 17032816
TI  - Evolution of the environmental contamination by thermophilic fungi in a turkey
      confinement house in France.
AB  - Fungal species constitute a major part of environmental contaminants in
      facilities where animals are housed. The present investigation was aimed at
      describing the relative abundances of fungal species and their concentrations in
      a turkey confinement house in France. Fungal cultures from poultry feed, litter,
      and air were undertaken every week throughout the 16-wk period of breeding. The
      incubation temperature of 40 degrees C was selected to isolate thermophilic
      fungal species (especially Aspergillus spp. and Candida albicans) that are
      potentially pathogenic for birds. The 2 species Aspergillus fumigatus and
      Aspergillus flavus were recovered at a mean of 10.5 and 37.0 cfu/m(3) of air
      sampled, respectively. Individual samplings yielded concentrations of up to 150.0
      cfu/m(3) for A. flavus in the first weeks of the investigation. Other fungal
      species were recovered at a mean of 18.9 cfu/m(3) (maximum 36.3 cfu/m(3)) in the
      air. The yeast C. albicans was first detected at wk 4 from litter samples and at
      wk 7 from poultry feed. Densities of C. albicans remained very high in litter
      samples (63.2 cfu/g) even after new litter was added at wk 10. To analyze the
      genetic polymorphism of A. fumigatus, the most pathogenic mold in birds, a total
      number of 198 isolates (134 from air, 34 from litter, and 30 from feed samples)
      were genotyped using 2 polymorphic microsatellite markers. More than half (42 out
      of 73, 57.5%) of the genotypes were detected only once. This finding suggests
      that the contamination of the breeding environment is not due to a single source
      and confirms the very high genetic diversity of environmental A. fumigatus
      isolates. As during the study period, no outbreak of fungal infections occurred;
      the levels of fungal contaminations reported here do not seem sufficient, at
      least alone, to trigger fungal infections.

PMID- 17032817
TI  - Effects of travel distance and the season of the year on death rates of broilers
      transported to poultry processing plants.
AB  - Death losses among broilers transported to processing plants are caused by poor
      welfare. The number of birds dying during transport and in processing plants
      shortly after arrival there may serve as an indicator of the quality of welfare
      during loading and transport. In the Czech Republic, shipments of broilers to
      processing plants were monitored from 1997 to 2004. It was found that the
      mortality of broilers during transport was 0.247%, but it varied according to the
      transport distance to the processing plant from 0.146% (50 km maximum) to 0.862%
      (>300 km). The broiler mortality in transit was also influenced by the season of
      the year. The highest mortality was found in summer months, especially in June,
      July, and August, and in winter months, especially in December, January, and
      February. A comparison between period 1 (1997 to 2000) and period 2 (2001 to
      2004) showed a long-term adverse trend in the number of broilers dying during
      transport to processing plants for all of the distances monitored (except
      transport distances <50 km), because the overall number of dead birds on arrival
      to processing plants increased from 0.224 to 0.265% (index of 1.18). This
      difference is statistically significant (P = 0.000). The stress caused to
      broilers by transport to processing plants is reflected in higher transport
      related mortality of the birds. Long-term trends point to an increase in death
      losses of broilers. Longer transport distances and transportation in summer and
      winter months have led to an increase in death losses among broilers transported
      to processing plants.

PMID- 17032818
TI  - Lack of estrogenic or antiestrogenic actions of soy isoflavones in an avian
      model: the Japanese quail.
AB  - Isoflavones are soy compounds that possess weak estrogenic and antiestrogenic
      activities. In addition, phytochemicals, including isoflavones, may play a role
      in regulating seasonal reproductive cycles. As soy is a common constituent in
      poultry diets, the effect of these compounds on the reproductive system of
      production birds may be of concern. The present study examined the putative
      effects of soy isoflavones supplemented into the diet at 1 and 5% using endpoints
      of growth and reproduction in the Japanese quail. Isoflavones did not exert an
      effect on growth, feed intake, growth:feed, or the weight of the estrogen
      sensitive immature oviduct in female quail. Furthermore, isoflavones did not
      influence the growth of the oviduct stimulated by exogenous estradiol. Similarly,
      isoflavones did not influence growth, feed intake, or growth:feed in male quail.
      However, isoflavones at 1%, but not 5%, in the diet reduced photoperiod-induced
      testis development 40% vs. control. In contrast, isoflavones did not influence
      testis regression stimulated by exogenous estradiol in sexually maturing male
      quail. The present results suggest that isoflavones may exert modest endocrine
      disruptor-like effects on reproduction in male, but not female, quail.

PMID- 17032819
TI  - Tissue expression and association with fatness traits of liver fatty acid-binding
      protein gene in chicken.
AB  - Fatty acid-binding proteins belong to a superfamily of lipid-binding proteins
      that exhibit a high affinity for long-chain fatty acids and appear to function in
      metabolism and intracellular transportation of lipids. The current study was
      designed to investigate expression characterization and association with growth
      and composition traits of the liver fatty acid-binding protein (L-FABP) gene in
      the chicken. Northern blot analysis indicated that the gene, similar to the
      mammal L-FABP gene, was expressed only in liver and intestinal tissues. The mRNA
      levels of the chicken L-FABP gene in liver and intestine had significant
      differences between the broilers and Baier layers. The China Agricultural
      University F(2) population was used in the present study. Body weight and body
      composition traits were measured in the populations. Primers for the coding
      region and 5' upstream region of the L-FABP gene were designed according to
      chicken genomic and cDNA sequence. Polymorphisms were detected by DNA sequencing,
      and the PCR single-strand conformation polymorphisms method was developed to
      genotype the F(2) population. The results indicated that the L-FABP gene
      polymorphisms were associated with abdominal fat weight and percentage of
      abdominal fat, and the L-FABP gene could be a candidate locus or linked to a
      major gene(s) that affects fatness traits in the chicken. The results of the
      current study provided basic molecular information for studying the role of the L
      FABP gene in the regulation of lipid metabolism in avian species.

PMID- 17032820
TI  - A potential molecular marker for selection against abdominal fatness in chickens.
AB  - The peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC
      1alpha) was investigated as a candidate gene for growth and fatness traits in
      chicken because of its prominent role in muscle fiber specialization and
      adipogenesis. A single nucleotide polymorphism (SNP) from G to A at position 646
      of the open reading frame of chicken PGC-1alpha gene causing an Asp216Asn amino
      acid substitution was identified. The frequencies of alleles and genotypes were
      significantly different among 6 chicken breeds (P < 0.01). The White Plymouth
      Rock had the highest frequency (0.67) of allele G, whereas the White Leghorn had
      the lowest (0.18). The associations of the SNP with the growth and fatness traits
      were evaluated in 332 F(2) birds from an experimental cross of White Plymouth
      Rock x Silkies. No association was found between the SNP and growth-related
      traits. However, abdominal fat weight at 12 wk of age for birds with genotype GG
      was 34.26 and 28.71% higher than those with genotypes AA and AG, respectively (P
      < 0.01), indicating that the Asp216Asn polymorphism of the PGC-1alpha gene could
      be used as a novel potential molecular marker for selection against abdominal
      fatness without interfering in regular breeding for growth rate of chickens.

PMID- 17032821
TI  - Upregulation of oxidative burst and degranulation in chicken heterophils
      stimulated with probiotic bacteria.
AB  - The immune system of neonatal chicks is functionally immature during the first
      week of life. Researchers have previously demonstrated that the avian humoral
      response can be increased with probiotics. Although the humoral response provides
      the chick with an effective mechanism to combat pathogens, sufficient antibody
      titers are not attained until 7 to 10 d postinfection. However, the innate immune
      system (i.e., heterophils) can respond much more quickly to pathogens. The
      objective of this study was to determine whether probiotic bacteria can also
      upregulate heterophil function. Heterophils were isolated from the peripheral
      blood of neonatal chickens by using a discontinuous density gradient. Oxidative
      burst and degranulation are bactericidal mechanisms used by heterophils to kill
      pathogens and were used in this study as indicators of heterophil function. We
      found that each of the 10 "generally recognized as safe" probiotic isolates
      (designated G1 to G11) tested in vitro were capable of increasing (P < 0.05)
      heterophil oxidative burst and degranulation when compared with unstimulated
      controls. Bacillus subtilis (G3), Lactococcus lactis lactis (G6), and
      Lactobacillus acidophilus (G8) isolates were determined to elicit the greatest
      heterophil response in vitro and were subsequently fed to chicks. Phosphate
      buffered saline or 1 of these 3 probiotic isolates (approximately 2.5 x 10(8)
      cfu/chick; 50 chicks/treatment) resuspended in PBS was administered by oral
      gavage on the day of hatch. Heterophils were isolated from chicks from each of
      these 4 treatment groups 24 h posttreatment. Significant increases in heterophil
      degranulation and oxidative burst were observed with the G3-, G6-, and G8-treated
      chicks when compared with heterophils isolated from birds with no probiotic
      treatment. These data suggest that probiotic bacteria can significantly improve
      heterophil oxidative burst and degranulation in broilers. To our knowledge, this
      is the first study demonstrating a relationship between probiotics and avian
      heterophil function.

PMID- 17032822
TI  - Cytokine expression in chicken peripheral blood mononuclear cells after in vitro
      exposure to Salmonella enterica serovar Enteritidis.
AB  - Cytokines are secreted proteins involved with cell recruitment and regulation of
      both innate and adaptive immune responses. They are essential for an effective
      host immune response to pathogens. The objective of this study was to determine
      the effect of Salmonella enterica serovar Enteritidis (S. Enteritidis) exposure
      and genetic line on cytokine mRNA expression level of cultured chicken peripheral
      blood mononuclear cells (PBMC). Interleukin-2, interleukin-6 (IL-6), CXCLi2, and
      transforming growth factor-beta4 (TGF-B4) messenger ribonucleic acid expression
      was measured by quantitative reverse transcription-PCR assays in PBMC from 3
      chicken lines (broiler, Leghorn, Fayoumi) after in vitro exposure to S.
      Enteritidis. The PBMC were isolated from uninfected birds and cultured overnight.
      The next day, live pathogenic S. Enteritidis was added to half of the cultures.
      All cultures were harvested after 2 or 4 h of exposure. Exposure to S.
      Enteritidis downregulated IL-6, CXCLi2, and TGF-beta4 but not interleukin-2 mRNA
      expression. No significant genetic line or exposure time effects were detected.
      These findings demonstrate that exposure of chicken PBMC to S. Enteritidis can
      induce a rapid change in both proinflammatory (IL-6, CXCLi2) and antiinflammatory
      (TGF-beta4) cytokine gene expression.

PMID- 17032823
TI  - Effects of cysteamine on growth performance, digestive enzyme activities, and
      metabolic hormones in broilers.
AB  - A total of 600 avian male broilers at the age of 1 d were used to investigate the
      effects of cysteamine (CSH) on growth performance, digestive enzyme activities,
      and concentrations of serum hormones. The broilers received the same basal diets,
      with CSH added at 0 (control), 60, 90, 120, or 150 mg/kg. The feeding program
      consisted of a starter diet until 21 d and a grower diet until 42 d. The broilers
      with addition of CSH at 60 or 90 mg/kg had significantly higher growth rates
      during d 1 to 21 or d 21 to 42 compared with the control, respectively. However,
      adding 150 mg of CSH/kg significantly suppressed the growth of broilers. Adding
      60 mg of CSH/kg significantly increased the activities of protease, amylase, and
      lipase in the pancreas and small intestinal contents during d 1 to 21, and the
      activities of protease and amylase in the small intestinal contents during d 21
      to 42. Adding 90 mg of CSH/kg significantly increased the activities of lipase
      during d 1 to 21 and protease, amylase, and lipase during d 21 to 42 in small
      intestines. The activities of digestive enzymes during the whole period were
      suppressed by adding 150 mg of CSH/kg. The concentration of serum thyroxine was
      higher in the CSH-added birds during the whole period, whereas serum
      triiodothyronine was higher only during d 1 to 21 compared with the control.
      These findings indicate that low doses of dietary CSH may improve the growth
      performance and the activities of the digestive enzyme, but high doses of CSH
      appear to be detrimental to growth and digestion.

PMID- 17032824
TI  - Relationship between bicarbonate retention and bone characteristics in broiler
      chickens.
AB  - Determination of the bicarbonate retention factor (BRF) is an important step
      during development of the indicator amino acid oxidation technique for use in a
      new model. A series of 4-h oxidation experiments were performed to determine the
      BRF of broilers aged 7, 14, 21, 28, 35, and 42 d using 4 birds per age group. A
      priming dose of 1.2 microCi of NaH(14)CO(3), followed by eight half-hourly doses
      of 1 microCi of NaH(14)CO(3) were given orally to each of 4 birds per age. The
      percentage of (14)C dose expired by the bird at a steady state was measured.
      These birds, as well as 12 additional birds matched for age and BW, were killed,
      and femur bone mineral density was measured by quantitative computed tomography
      to determine the relationship between bone development and bicarbonate retention
      at each age. There was a correlation (r = 0.50; P < 0.05) between total cross
      sectional femur bone mineral density and bicarbonate retention at each age. A
      prediction equation (Y = 6.95 x 10(-2)X - 3.51 x 10(-5)X(2) + 27.58; P < 0.0001,
      R(2) = 0.79) where Y = bicarbonate retention and X = BW was generated to predict
      Y as a function of X. Bicarbonate retention values peaked at 28 d, during the
      stage of the most rapid bone deposition and the highest growth rate. A constant
      BRF was found from 1,900 to 2,700 g of BW of 35.15 +/- 1.095% (mean +/- SEM).
      This retention factor will allow the accurate correction of oxidation of (14)C
      labeled substrates in broilers of different ages and BW in future indicator amino
      acid oxidation studies.

PMID- 17032825
TI  - Response of broilers to feeding low-calcium and phosphorus diets plus phytase
      under different environmental conditions: body weight and tibiotarsus
      mineralization.
AB  - Three experiments on Ross broiler chickens were conducted in 3 locations: cages
      (Experiment 1), floor pens (Experiment 2), and commercial farms (Experiment 3).
      The effect of low-total P (TP) wheat-soybean based diets plus microbial phytase
      (Natuphos) was evaluated. Four experimental starter and finisher diets were used
      in a 2-phase feeding program, as follows: control diet (SC until 21 d, FC from 22
      to 42 d); 2 diets (SL400 and SL600 until 21 d, FL400 and FL600 from 22 to 42 d)
      with low TP (0.61% for starter and 0.54% for finisher), including 400 and 600
      U/kg of phytase, respectively; and a very low-TP (0.52% for starter and 0.44% for
      finisher) diet (SVL600 until 21 d, FVL600 from 22 to 42 d) with 600 U/kg of
      phytase. In Experiment 1 (broilers in cages had movement limitation and no access
      to litter), no differences in BW, tibiotarsus mineralization, or mineral
      metabolism were observed among diets. In Experiment 2 (broilers in floor pens had
      movement limitation and access to litter), at 21 d of age, the lowest tibiotarsus
      ash percentage and BW were shown by birds fed the SVL600 diet. At 42 d of age,
      broilers fed the FC diet were the lightest. For the rest of the parameters of
      tibiotarsus mineralization and mineral metabolism measured in Experiment 2, no
      differences were shown. In Experiment 3 (broilers in commercial farms had access
      to litter without movement limitation), the BW of broilers fed the SC diet was
      the highest at 21 d of age. At 42 d of age, the broilers fed FL400 and FL600
      diets were the heaviest. At the end of Experiment 3, broilers fed the FC diet had
      the highest dry litter Ca and P, whereas broilers fed the FVL600 diet had the
      lowest values. In conclusion, the very low-TP wheat-soybean based diet
      supplemented with 600 U/kg of phytase was sufficient to optimize all the
      parameters measured in Experiment 1 but not in Experiments 2 and 3. Therefore,
      when evaluating Ca and P in phytase-supplemented diets for broilers, it is
      necessary to bear in mind the environmental conditions of experimentation.

PMID- 17032826
TI  - Conversion of the methionine hydroxy analogue DL-2-hydroxy-(4-methylthio)
      butanoic acid to sulfur-containing amino acids in the chicken small intestine.
AB  - dl-Methionine or its corresponding hydroxy analogue, DL-2-hydroxy-(4-methylthio)
      butanoic acid (DLHMB), are commonly added to commercial animal diets to satisfy
      the TSAA requirement. The utilization of DLHMB as a supplementary source of Met
      begins with its conversion to L-Met via a 2-step mediated process. L-Methionine
      can then be transsulfurated to L-Cys, which, in turn, can be catabolized to
      taurine (TAU). In the present study, the capacity of the chicken small intestine
      to convert DLHMB to L-Met and to use this amino acid as a source for L-Cys and
      TAU production was evaluated. The appearance of Met in the serosal compartment of
      everted sacs incubated with DLHMB is higher in the presence of an H(+) gradient
      (mucosal pH 5.5 vs. 7.4). Serosal Cys and TAU concentration was compared in
      everted sacs incubated at a mucosal pH of 5.5 with DLHMB or L-Met, and the
      results show significantly higher values after incubation with the hydroxy
      analogue. Regional comparisons indicate no significant differences in the
      appearance of serosal Met and Cys, although lower values were obtained for TAU in
      the duodenum than in the jejunum and ileum. The profile of non-S amino acids was
      also determined and revealed no significant differences between DLHMB- and L-Met
      incubated sacs. In conclusion, Cys and TAU content in chicken enterocytes is
      higher when DLHMB is used as a Met source.

PMID- 17032827
TI  - The effect of feeding calcium- and phosphorus-deficient diets to broiler chickens
      during the starting and growing-finishing phases on carcass quality.
AB  - There is considerable data on the effect of reducing inorganic Ca and P in
      broiler finisher diets on carcass quality. However, there is limited information
      on the effect of reducing dietary Ca and P during the different phases of
      growout. Two experiments were conducted from 0 to 35 d in floor pens. In both
      experiments, at least 4 replicates per treatment (50 chicks per replicate) were
      used. Corn-soybean meal and soybean oil-based diets deficient in Ca and P were
      fed. During the starter phase (ST), from 0 to 18 d, chicks were fed a 23% CP diet
      containing 0.60% Ca and 0.47% total P (tP). During the grower-finisher phase
      (GF), from 19 to 35 d, birds were fed a 19% CP diet containing 0.30% Ca and 0.37%
      tP. A combination of 1,000 phytase units/kg of Natuphos phytase and 5 microg/kg
      of 1alpha-hydroxycholecalciferol (P + 1alpha) was supplemented to some of the
      feed during the ST and GF. Diets containing adequate Ca and P were also fed
      during the ST (0.90% Ca and 0.68% tP) and GF (0.80% Ca and 0.67% tP). The level
      of tibia ash and the incidence of bone disease were measured at 18 and 35 d. At
      the end of the experiments, birds were processed and evaluated for muscle
      hemorrhages and broken bones. In both experiments, broilers fed diets that were
      not P + 1alpha supplemented demonstrated poor bone mineralization, considerable
      leg problems, and a high incidence of broken bones after processing. Broilers fed
      P + 1alpha throughout had more broken clavicles and femurs compared with birds
      fed the adequate diets. Day-18 tibia ash was significantly correlated to broken
      tibias and femurs during processing. Day-35 tibia ash was better correlated to
      bloody breast meat than to broken bones. It is concluded that carcass quality
      depends on the levels of Ca and P fed and the age of the bird. Tibia ash,
      traditionally used as an indication of bone strength, was better correlated to
      the incidence of bloody breasts.

PMID- 17032828
TI  - Effect of manganese source on manganese absorption by the intestine of broilers.
AB  - Two experiments were conducted to investigate the effect of Mn source on Mn
      absorption by the intestine of broilers. In Experiment 1, the effect of Mn
      source, including MnSO(4), 2 Mn-amino acid chelates (Mn-Gly and Mn-Met)
      synthesized in our laboratory, 3 Mn-amino acid complexes with different complex
      strengths (Mn-Met E, Mn-AA A, and Mn-AA B), and 2 mixtures of MnSO(4) with Gly or
      Met, on Mn absorption was assessed with ligated loops of different small
      intestinal segments of broilers. In Experiment 2, the absorption of Mn from
      MnSO(4), Mn-AA A, and Mn-AA B was compared with intact broilers fed ad libitum.
      The criterion used for comparison was the Mn content of hepatic portal vein
      plasma. The absorption of Mn was higher (P < 0.0002) by ligated ileal loops than
      by duodenal and jejunal ones. Met supplementation increased (P < 0.03) the
      absorption of Mn as MnSO(4). The absorption of Mn as Mn-AA A and Mn-AA B with
      moderate and strong complex strengths, respectively, were higher (P < 0.05) than
      those of Mn as MnSO(4) and Mn-Met E with weak complex strength. On d 7 and 9 of
      Experiment 2, the Mn content of portal vein plasma was higher (P < 0.03) for Mn
      AA B with strong complex strength than for MnSO(4). On d 9, Mn content in plasma
      was higher (P < 0.01) for Mn-AA B with strong complex strength than for Mn-AA A
      with a moderate one. The results from this study confirm that the ileum was the
      main site of Mn absorption for broilers, and Met was more effective in
      facilitating Mn absorption than Gly as a ligand. Organic Mn was more efficiently
      absorbed than inorganic Mn (MnSO(4)); the absorption of organic Mn with moderate
      and strong complex strengths was greater than that of the organic Mn, which was
      weak, and the absorption of organic Mn with strong complex strength was greater
      than that of the organic Mn with a moderate strength.

PMID- 17032829
TI  - Comparison of amino acid digestibility in broiler chickens, turkeys, and Pekin
      ducks.
AB  - The objective of this study was to compare prececal amino acid (AA)
      digestibilities in broilers, turkeys, and Pekin ducks that were 3 wk old. Five
      diets were used: a basal diet and diets that contained either soybean meal (SBM)
      or rapeseed meal (RSM) at the expense of starch each at either 150 or 300 g/kg.
      The differences in dietary CP and AA concentrations resulted only from the
      inclusion of SBM or RSM. Titanium dioxide was used as an indigestible marker.
      Each diet was allocated to 6 pens of 12 birds from each species and provided ad
      libitum for 1 wk starting at 14 d of age. Digesta were sampled on a pen basis
      from the distal two-thirds of the section between Meckel's diverticulum and 2 cm
      anterior to the ileocecocolonic junction. Ingested and digested amounts of AA
      were determined for each pen. Digestibilities for the 2 meals were then
      determined by a multiple linear regression analysis, which makes a correction for
      basal endogenous AA losses unnecessary. Digestibilities for essential AA from the
      meals varied between 92% (Met, RSM, broilers) and 62% (Val, RSM, ducks).
      Digestibilities were not significantly different between SBM and RSM for broilers
      and turkeys, but the average digestibility across all AA was slightly higher for
      SBM and lower for RSM in turkeys than in broilers. Digestibilities were lower in
      ducks than in the 2 other species, and significant differences between SBM and
      RSM were detected for some AA in ducks. Amino acid digestibility ranking was very
      similar between broilers and turkeys but different for the 2 meals. It was
      concluded that differences among species cannot be explained by differences in
      basal endogenous AA losses among species. Amino acid digestibilities determined
      with broilers should not be used in formulating feed for ducks.

PMID- 17032830
TI  - Modeling of threonine requirement in fast-growing chickens, depending on age,
      sex, protein deposition, and dietary threonine efficiency.
AB  - In addition to dose-response studies, modeling of N utilization, depending on
      intake of the first limiting amino acid in the diet, is one of the tools for
      assessing amino acid requirements in growing animals. Based on a verified
      nonlinear N-utilization model and following the principles of the diet dilution
      technique, N-balance experiments were conducted to estimate the Thr requirement
      of fast-growing chickens (genotype Cobb), depending on age, sex, CP deposition.
      and efficiency of dietary Thr utilization. Different predictions were made for
      the feed intake to conclude the optimal Thr concentration in the feed. The
      results are based on N-balance experiments with a total of 144 male and 144
      female growing chickens within 4 age periods (I: 10 to 25 d; II: 30 to 45 d; III:
      50 to 65 d; IV: 70 to 85 d), using diets with graded protein supply (6.6, 13,
      19.6, 25.1, 31.8, and 37.6% CP in DM) from high-protein soybean meal with a
      constant amino acid ratio and Thr as the first limiting amino acid (3.87 g of
      Thr/100 g of CP; dietary Lys:Thr = 1:0.54). The observed optimal Thr
      concentration (% of feed) was influenced by age, sex, level of CP deposition,
      dietary efficiency of Thr utilization, and predicted feed intake. For male
      chickens, assuming an average CP deposition (60% of the potential) and average
      efficiency of Thr utilization, 0.78% (10 to 25 d), 0.73% (30 to 45 d), 0.65% (50
      to 65 d), and 0.55% (70 to 85 d) total dietary Thr were observed as optimal total
      Thr concentration in the diet (corresponding to 60, 135, 160, and 180 g of daily
      feed intake, respectively). Data are discussed in context with the main factors
      of influence like age, sex, level of daily CP deposition, efficiency of dietary
      Thr utilization, and predicted feed intake.

PMID- 17032831
TI  - Spontaneously occurring fibroid tumors of the laying hen oviduct.
AB  - Spontaneously occurring benign uterine leiomyomas (fibroids) are the most common
      tumors of reproductive-age women. It is estimated that more than 70% of all women
      will develop uterine fibroids, and the presence of these tumors is a primary
      cause of hysterectomies. Research into the causes and treatment of uterine
      fibroids is hampered by a lack of reliable animal models for the disease.
      Leiomyomas that appear to be outwardly similar to human uterine fibroid tumors
      are known to occur on the oviducts of laying hens over 2 yr of age. The objective
      of this study was to characterize these tumors and compare them to human uterine
      fibroids to determine the suitability of the aging hen as a model system for the
      study of the disease. In this study, hens at 5 yr of age were examined for the
      presence of oviduct-associated fibroid tumors. Tumors were found attached to the
      internal surface of the oviduct, embedded in the oviduct wall, or attached to the
      exterior of the magnum and isthmus. Tumor and normal oviduct samples were frozen
      or fixed in formalin for histological analyses or immunohistochemistry for
      estrogen and progesterone receptors, proliferating cell nuclear antigen and Bcl-2
      protein expression. Human uterine fibroid samples were acquired and evaluated
      compared with hen oviduct fibroids. The results indicate that laying hen fibroid
      tumors are similar to human fibroid tumors with respect to estrogen and
      progesterone receptors, localized cellular proliferation, and expression of the
      Bcl-2 protein.

PMID- 17032832
TI  - Effects of caponization and different exogenous androgen on the bone
      characteristics of male chickens.
AB  - The effects of caponization and androgen implantation on the bone characteristics
      of male chickens were evaluated. Healthy Single Comb White Leghorn cockerels were
      caponized or sham operated (sham) at 12 wk old. Sixteen birds from each group
      were selected for a 14-wk experiment in trial 1. Sixteen birds from the sham
      group and 64 from the caponized group (randomly allocated into 4 treatments) were
      implanted with 10.4 +/- 0.4 mg (1.62-mm i.d., 3.6-mm o.d.) of cholesterol,
      testosterone (TES), 5alpha-dihydrotestosterone (5alpha-DHT), or 19
      nortestosterone (19-NorT) and were assigned to trial 2 for a 14-wk experiment.
      The results from trial 1 showed that caponization increased BW (P < 0.05) and
      decreased tibia stress, ash content, and P content with higher blood P
      concentration (P < 0.05) as compared with the sham group. In trial 2, the
      cholesterol implantation group showed the lowest tibia breaking strength, bending
      moment, stress, and ash content (P < 0.05). The 19-NorT implantation group showed
      decreased (P < 0.05) blood Ca and P concentration but increased tibia ash and P
      content, reaching the same level as the sham group (P > 0.05). The adverse
      effects of caponization on bone characteristics could be improved using androgen
      implantation. Among the implantation groups, the 19-NorT implantation group
      showed the best improvement in tibia breaking strength and bending moment,
      followed by the TES and 5alpha-DHT groups. The TES group showed the best
      improvement in tibia stress, followed by the 19-NorT and 5alpha-DHT groups.

PMID- 17032833
TI  - Adaptation of epithelial sodium-dependent phosphate transport in jejunum and
      kidney of hens to variations in dietary phosphorus intake.
AB  - The objective of this study was to explore the homeostatic response of jejunal
      and renal epithelia regarding the inorganic phosphate (P(i)) transport capacities
      to variations in dietary total phosphorus (tP) supply in hens. Adaptive processes
      were determined by quantitative measures of intake and excretion, P(i) transport
      studies across brush border membranes, and semiquantitative detection of sodium
      dependent phosphate transporters (NaPi II) based on mRNA expression in the
      jejunum and kidney. Twelve hens (4/group) were adapted to 3 tP feeding levels in
      a pair-fed manner (60 g/d): low P diet with 0.073% tP, medium P diet with 0.204%
      tP, and high P diet with 0.343% tP. Excretion was measured during the last 5 d of
      a 16-d feeding period. After slaughtering, jejunal mucosa and renal cortex were
      removed. Tissues were used for (32)P uptake studies in brush-border membrane
      vesicles by rapid filtration technique and NaPi II mRNA expression studies by
      northern analyses. Plasma P(i) concentrations were additionally measured. The
      NaPi II transporter mRNA could specifically be detected in chicken jejunum and
      kidney. Functional parameters of Na(+)-dependent P(i) transport indicated that
      these transporters were involved in chicken P(i) transport across the apical
      membranes of jejunal and renal epithelia. Increased tP intake resulted in an
      increased overall tP excretion. Correlating individual data from all animals by
      linear regression highlighted that the adaptive decrease of renal P(i) transport
      capacity and NaPi IIa mRNA expression was associated with an increase in plasma
      P(i) levels and resulted in a higher tP excretion. Jejunal P(i) transport
      capacity and NaPi IIb mRNA expression did not react to variations in dietary tP
      supply. In conclusion, the homeostatic response was mainly based on the adaptive
      capacity of the kidney in hens.

PMID- 17032834
TI  - Age-related changes in the distribution of lean fat with skin and bones in goose
      carcasses.
AB  - The experimental materials comprised White Italian geese (128 males and 128
      females) reared to 14 wk of age. The birds were fed standard diets ad libitum.
      Starting from 2 wk of age, 14 males and 14 females were killed at 2-wk intervals.
      The carcasses were divided into neck, wings, legs, breast, and back, which were
      then dissected into muscle, skin with fat, and bones. Before slaughter, the BW of
      males and females were 6,814 and 5,736 g, respectively. At 2 wk of age, more than
      half of total muscle content was in the legs (60.98%), and the rest was in the
      back (17.84%), neck (9.43%), breast (8.78%), and wings (2.97%). To 10 wk of age,
      the rate of muscle deposition was relatively slow in the legs (a decrease to
      31.29%) and fast in the breast and wings (an increase to 34.12 and 12.90%,
      respectively). Age-related changes in the distribution of skin with fat in the
      carcass were smaller, compared with changes in muscle distribution. A rising
      tendency was observed in the muscle content of wings and breast and in the
      content of skin with fat in the wings and neck, whereas a falling tendency was
      observed in the other carcass parts. Over the first 8 wk, the proportion of bones
      decreased in the legs, back, and neck and increased in the wings and breast, as
      compared with the total bone weight in the carcass.

PMID- 17032835
TI  - Incidence of pectoralis major turkey muscles with light and dark color in a
      Portuguese slaughterhouse.
AB  - Turkey meat and processed products are very popular in Portugal. However, no
      studies have been made to assess turkey meat quality. The main objective of this
      study was to evaluate the quality of turkey breast meat in a Portuguese
      slaughterhouse, differentiating it to obtain better industrial management,
      performance, and consumer contentment. Nine hundred and seventy-seven male
      turkeys (from 16 to 20 wk old) from different flocks (BUT 9 and BIG 6) were
      evaluated to assess meat quality. Turkeys were slaughtered on different days,
      electrically stunned (225 V/3 s), and scalded in a vertical water bath at 81
      degrees C/5 min. On the slaughter line, the pH and temperature were measured on
      the pectoralis muscle 15 min postmortem. The carcasses were fast-cooled in a
      tunnel (-2 degrees C/2 m.s(-1)/90% RH) for 2 h and kept in a refrigeration
      chamber (0 degree C/85% RH) until deboning (approximately 24 h postmortem). Color
      and pH 24 h postmortem (pH(24)) were measured on the pectoralis major muscle
      after carcass deboning. Pectoralis major muscles were selected according to
      criteria used by Barbut (1996) and drip loss, cooking loss, and total pigments
      analysis were performed on 67 different sliced meat samples. Muscles classified
      by pH decline rate, called rapid glycolytic, did not present final quality
      characteristics that could relate them with pale, soft, and exudative- (PSE) like
      meat, because there was no relationship between pH 15 h postmortem and lightness
      (L*), drip loss, or cooking loss. The differences, founded on physicochemical
      characteristics within pectoralis major muscles, allowed us to establish a
      criteria of turkey meat quality for dark and PSE-like meat, with L* < or = 44 and
      pH(24) > or = 5.8 and L* > or = 50 and pH(24) < 5.8, respectively. Based on
      criteria, the studied population presented 8.1% of carcasses with PSE-like
      muscles and 12.1% with dark muscles. The association of pH(24) and L* as criteria
      classification can be useful to classify turkey meat quality.

PMID- 17032836
TI  - Microcracks in eggs.
AB  - An experimental program of mechanical testing has shown that microcracks initiate
      in hens' eggs at loads less than that necessary to cause total structural
      failure. In contact loading, computational modeling and numerical analysis show
      that very high stress levels develop on the inner surface of the eggshell as it
      conforms to a hard contact surface. This causes a series of microcracks to
      initiate at the inner surface of the shell and radiate out from the load site. A
      series of concentric circumferential microcracks also develop beneath the cuticle
      from the edge of the contact zone. Calculations relating to the eggshells'
      dynamic response indicate that microcracks have a little effect on the structural
      stiffness and resonant frequencies of the egg. As a result, microcracks are
      unlikely to be detected by online crack detection systems, which rely on
      mechanical excitation. Eggs in retail outlets are likely to contain microcracks
      as a result of insults experienced during the collection, grading, and packing
      processes. Because the eggshell forms the first line of defense against
      potentially pathogenic microorganisms entering the egg contents, microcracks
      could potentially compromise egg safety.

PMID- 17032837
TI  - Effect of oral administration of bismuth compounds on Campylobacter colonization
      in broilers.
AB  - Bismuth compounds have been used since the 18th century to treat gastrointestinal
      ailments in man. Colloidal bismuth subcitrate (De-Nol) is currently used in
      combination with antibiotics to reduce enteric Helicobacter pylori colonization
      as a treatment of stomach ulcers. We investigated whether bismuth citrate or its
      parent compound, colloidal bismuth subcitrate, would reduce colonization of the
      closely related foodborne pathogen, Campylobacter jejuni in chickens. In 2
      studies, birds were either fed 0, 50, or 200 ppm bismuth citrate or bismuth
      subcitrate (De-Nol) for 10 or 21 d and were orally challenged with 7 combined
      strains of C. jejuni (n = 6 birds/treatment). For both treatment groups, cecal
      Campylobacter colonization was reduced when birds were fed 200 ppm for 10 d but
      not 21 d. For the 50 ppm treatment group, only birds dosed with bismuth citrate
      for 21 d demonstrated any reduction in cecal Campylobacter concentrations when
      compared with controls. These data suggest that bismuth citrate and colloidal
      bismuth subcitrate may reduce cecal colonization by Campylobacter in broilers,
      but these effects are inconsistent.

PMID- 17032838
TI  - Effects of S6-strain Mycoplasma gallisepticum inoculation at ten, twenty-two, or
      forty-five weeks of age on the blood characteristics of commercial egg-laying
      hens.
AB  - In 2 consecutive trials of the current study, the effect of the age of
      application of S6-strain Mycoplasma gallisepticum (S6MG) inoculation on the blood
      characteristics of commercial layers housed and maintained under controlled
      conditions was determined. The ages of inoculation compared were those before lay
      at 10 wk of age, during onset of lay at 22 wk of age, and during postpeak lay at
      45 wk of age. In each trial, hematocrit, plasma protein, and serum cholesterol,
      triglycerides, and Ca were determined at 20, 24, 32, 43, 47, and 58 wk of age.
      The data from both trials were pooled then analyzed together, whereas, data from
      wk 20 (effect of 10-wk S6MG inoculation); data from wk 24, 32, and 43 (effects of
      10- and 22-wk S6MG inoculations); and data from wk 47 and 58 (effects of 10-, 22
      , and 45-wk S6MG inoculations) were analyzed separately. At wk 20, hematocrit was
      higher in birds inoculated with S6MG at 10 wk compared with sham-inoculated
      birds, and across wk 24, 32, and 43, serum Ca was higher in birds inoculated with
      S6MG at 10 or 22 wk compared with those that were sham-inoculated. Serum Ca level
      across wk 47 and 58 was higher in birds inoculated with S6MG at 10 wk compared
      with sham-inoculated controls and birds inoculated with S6MG at 22 wk, with 45-wk
      S6MG-inoculated birds being intermediate. The response of serum cholesterol level
      at 47 wk to S6MG inoculation at either 10, 22, or 45 wk compared with controls
      was nearly opposite to that of the response observed at 58 wk. However, serum
      triglycerides were depressed only at wk 47 due to the 45-wk S6MG inoculation
      compared with all other treatments. Variable post-peak alterations in serum Ca
      and lipids occur in response to the timing of S6MG inoculation in layers housed
      under controlled conditions.

PMID- 17032839
TI  - Consumers' preferences toward techniques for improving manual catching of
      poultry.
AB  - Growing interest in ameliorating animal welfare has prompted numerous studies
      that compare various aspects of manual and mechanical catching. In general,
      mechanical catching has been adopted as a realistic alternative for manual
      catching. The success of a catching machine as an alternative for manual catching
      does not only depend on its practical applicability, but also on its acceptance
      by "the general public." In the history of technological change, public
      perception of new technologies has often been ambivalent. Against this
      background, it is important to know how consumers perceive the production
      methods. This paper provides an evaluation of the preferences for catching
      methods by "society" to investigate whether there is a shift in preference due to
      the confrontation with video segments and the potential effect of awareness and
      importance attached to animal welfare on preference. Data were gathered through a
      questionnaire-based survey, including 450 respondents, performed in Belgium. For
      this study, the data indicated that when subjects were provided information
      concerning catching methods of broilers, they liked the technology much more.
      However, for those respondents without prior awareness of both catching methods
      or with high importance attached to animal welfare, giving information could not
      convince them of the advantage of using a mechanical catching machine. It is
      obvious that preference varies with the awareness and experience of the
      respondents. Future research should move forward from simple assessments of
      consumer concerns about the technologies and focus more directly on questions and
      issues related to the consumer's expected bottlenecks of these technologies. In
      this way, working at a better understanding can directly influence the acceptance
      of these technologies.

PMID- 17032840
TI  - Fine-mapping of coccidia-resistant quantitative trait loci in chickens.
AB  - Two commercial, pure broiler lines with different susceptibility to coccidiosis
      were used to fine-map QTL associated with the previously identified marker
      LEI0101, located at 259 cM on chromosome 1 and shown to be significantly
      associated with disease resistance. Eight additional microsatellite markers
      linked to LEI0101 were used for genotyping of F(1) parents and F(2) offspring (n
      = 314), and their associations with oocyst shedding, as a marker of disease
      resistance, were determined in birds experimentally infected with Eimeria maxima.
      Single-point analysis of 4 families showed that logarithm of odds (LOD) scores at
      all marker loci were > 0.5, with the exception of marker LEI0071, located at 242
      cM (LOD score = 2.45). Multipoint analysis showed a maximum LOD score between
      LEI0071 and LEI0101 at 254 cM (LOD score = 3.74). Although the LEI0071 marker was
      mapped near LEI0101 by linkage analysis, the physical location of LEI0071 was not
      identified. Further studies to determine the physical locations of these and
      other markers will allow additional application association mapping techniques
      using single nucleotide polymorphism markers.

PMID- 17032841
TI  - Molecular cloning, genomic organization, and expression of three chicken 5'-AMP
      activated protein kinase gamma subunit genes.
AB  - The 5'-AMP-activated protein kinase (AMPK) plays a key role in regulating
      cellular energy homeostasis. The AMPK is a heterotrimeric enzyme complex that
      consists of 1 catalytic (alpha) and 2 regulatory (beta and gamma) subunits.
      Mutations of the gamma subunit genes are known to affect AMPK functioning. In
      this study, we characterized the genomic organization and expression of 3 chicken
      AMPK gamma subunit genes (cPRKAG). Alternative splicing of the second exon of the
      cPRKAG1 gene resulted in 2 transcript variants that code for predicted proteins
      of 298 and 276 amino acids. Use of an alternate promoter and alternative splicing
      of the cPRKAG2 gene resulted in 4 transcript variants that code for predicted
      proteins of 567, 452, 328, and 158 amino acids. Alternative splicing of exon 3 of
      the cPRKAG3 gene resulted in the production of "long" and "short" transcript
      variants that code for predicted proteins of 382 and 378 amino acids,
      respectively. We found evidence for differential expression of individual gamma
      subunit gene transcript variants and, in some cases, tissue-specific expression
      was observed. The cPRKAG subunit genes displayed similar structural features and
      high sequence homology compared with corresponding mammalian gamma subunit gene
      homologues.

PMID- 17032842
TI  - The three and one-half year radiology residency.

PMID- 17032843
TI  - Dural tail: another face of facial nerve schwannoma?

PMID- 17032844
TI  - A case meeting clinical brain death criteria with residual cerebral perfusion.

PMID- 17032845
TI  - Radiation worker mortality: intersociety call for survey participation.

PMID- 17032846
TI  - Magnetic resonance imaging of the fetal brain and spine: an increasingly
      important tool in prenatal diagnosis: part 2.
AB  - Fetal MR imaging is an increasingly available technique used to evaluate the
      fetal brain and spine. This is made possible by recent advances in technology,
      such as rapid pulse sequences, parallel imaging, and advances in coil design.
      This provides a unique opportunity to evaluate processes that cannot be
      approached by any other current imaging technique, and it affords a unique
      opportunity for studying in vivo brain development and early diagnosis of
      congenital abnormalities inadequately visualized or undetectable by prenatal
      sonography. This 2-part review summarizes some of the latest developments in MR
      imaging of the fetal brain and spine and its application to prenatal diagnosis.
      The first part discussed the utility, safety, and technical aspects of fetal MR
      imaging; the appearance of normal fetal brain development; and the role of fetal
      MR imaging in the evaluation of fetal ventriculomegaly. In this second part, we
      focus on additional clinical applications of fetal MR imaging, including
      suspected abnormalities of the corpus callosum, malformations of cortical
      development, and spine abnormalities.

PMID- 17032847
TI  - Restricted diffusion in bilateral optic nerves and retinas as an indicator of
      venous ischemia caused by cavernous sinus thrombophlebitis.
AB  - A 44-year-old man developed bilateral blindness following severe periorbital
      cellulitis and pansinusitis. CT and MR imaging demonstrated bilateral cavernous
      sinus thrombosis. Diffusion-weighted imaging revealed reduced apparent diffusion
      coefficient in bilateral optic nerves, suggesting optic nerve ischemia caused by
      the cavernous sinus thrombophlebitis (CST). Following surgical debridement of
      pansinusitis, antimicrobial therapy, and anticoagulation, the patient recovered
      from the infectious episode but sustained permanent bilateral blindness. This
      case shows that both retinal and optic nerve ischemia can be the cause of
      blindness after CST. Arguments supporting an arterial-versus-venous origin for
      the ischemia are discussed.

PMID- 17032848
TI  - Fluoroscopic and CT fistulography of the first branchial cleft.
AB  - We present an unusual case of a complete first branchial cleft fistula
      communicating between the external auditory canal and the skin near the angle of
      the mandible. CT and fluoroscopic fistulography were used to establish the
      presence and course of the tract and to assist in surgical planning. The
      embryology and classification of first branchial cleft anomalies are discussed,
      with emphasis on the impact of imaging.

PMID- 17032849
TI  - Nasopharyngeal extension of glomus tympanicum: an unusual clinical and imaging
      manifestation.
AB  - Nasopharyngeal extension of the glomus tympanicum is rare. Only 2 cases have been
      reported in the literature to date. We present a reported case of a large
      nasopharyngeal extension of recurrent glomus tympanicum, with various kinds of
      imaging and histopathology and a review of the literature.

PMID- 17032850
TI  - Neurothekeoma of the tongue: CT, MR, and FDG PET imaging findings.
AB  - We report CT, MR, and fluorodeoxyglucose-positron-emission tomography (FDG-PET)
      imaging findings of a case of cellular neurothekeoma of the tongue, a rare benign
      soft-tissue tumor with neural differentiation, occurring in a 15-year-old girl.
      CT and MR imaging showed a well-defined, well-enhancing submucosal soft-tissue
      mass in the midline dorsal tongue. There was high FDG uptake on PET scans.
      Although imaging findings are rather nonspecific, neurothekeoma may be one of
      diagnostic inclusions of soft-tissue masses of the tongue in a young female
      patient.

PMID- 17032851
TI  - Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.
AB  - We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar
      base that required a differential diagnosis because of clinical features and MR
      images that resembled the nasolabial cyst. The morphologic analysis on MR images
      revealed the characteristic appearance of the nasolabial cyst, and the sagittal
      MR image may be most helpful for diagnosing this rare disease.

PMID- 17032852
TI  - Cerebral ischemia after filter-protected carotid artery stenting is common and
      cannot be predicted by the presence of substantial amount of debris captured by
      the filter device.
AB  - PURPOSE: Protected carotid artery stent placement is currently under clinical
      evaluation as a potential alternative to carotid endarterectomy. The current
      study was undertaken to determine the incidence of new ischemic lesions found on
      diffusion-weighted MR imaging (DWI) in nonselected patients after protected
      carotid artery stent placement using a filter device and to determine the
      potential relationship between these new ischemic lesions and the presence or
      absence of a clear amount of debris captured by the neuroprotection filter
      device. MATERIALS AND METHODS: A nonrandomized cohort of 52 patients (40 men, 12
      women) presenting with carotid occlusive disease underwent protected carotid
      artery stent placement using a filter device. DWI obtained 1 day before stent
      placement was compared with that obtained 1 day after stent placement. In
      addition, the macroscopic and microscopic analysis of debris captured by the
      filter device during the carotid stent placement procedure was assessed. RESULTS:
      Neuroprotected carotid stent placement was technically successful in all 53
      procedures but was complicated by a transient ischemic attack in 3 patients
      (5.6%). In 22 patients (41.5%), new ischemic lesions were found on DWI, and in 21
      filter devices (39.6%), a substantial amount of atheromatous plaque and/or fibrin
      was found. No clear relationship between the presence of debris captured by the
      filter device and new lesions detected by DWI was found (P = .087; odds ratio
      3.067). CONCLUSION: Neuroprotected carotid artery stent placement will not avoid
      silent cerebral ischemia. Systematic microscopic analysis of debris captured by
      the filter device has no predictive value for potential cerebral ischemia after
      carotid artery stent placement.

PMID- 17032853
TI  - Treatment of cerebral aneurysms with hydrogel-coated platinum coils (HydroCoil):
      early single-center experience.
AB  - PURPOSE: The authors report their experience using HydroCoils in the treatment of
      cerebral aneurysms. METHODS: We performed a retrospective review of the first 100
      nonrandomized patients (104 coiled saccular cerebral aneurysms) treated with
      HydroCoils during a 27-month period. RESULTS: The average percentage of HydroCoil
      by length detached in treated aneurysms was 45.5% (range, 9.9-100%). Immediate
      postprocedure angiography demonstrated complete aneurysm occlusion in 34%, neck
      remnant in 35%, and incomplete occlusion in 32%. Immediate procedure-related
      morbidity and mortality rates were 5.8% and 0%, respectively. Angiographic follow
      up was obtained in 51% (51/100 patients; 53/104 aneurysms; average, 10.3 months;
      range, 0-31 months). In these 53 angiographically followed aneurysms, the overall
      recanalization rate was 21%: no recanalization occurred in 23 aneurysms with
      small size (<10 mm)/small neck (<4 mm) (S/S); 4 recanalizations occurred in 7
      aneurysms with small size/wide neck (>4 mm) (S/W); 6 recanalizations (27%)
      occurred in 22 large (L) aneurysms (>10-25 mm, 70% angiographic follow-up); and 1
      giant (G) (>25 mm) aneurysm recanalized. A large proportion of aneurysms that
      were not initially completely occluded were completely occluded on follow-up
      (15/43 [35%]). Clinical follow-up was obtained in 73 patients (73%; average, 5.3
      months; range, 0-24 months): 93% of these patients were neurologically improved
      or unchanged. Three patients rehemorrhaged and 3 patients with unruptured
      aneurysms developed delayed hydrocephalus. CONCLUSIONS: The overall safety
      profile of HydroCoils appears acceptable. Preliminary midterm observations
      suggest less coil compaction/aneurysm recanalization in large aneurysms. However,
      HydroCoil-related delayed hydrocephalus is a concern.

PMID- 17032854
TI  - Guglielmi detachable coils versus matrix coils: a comparison of the immediate
      posttreatment results of the embolization of 364 cerebral aneurysms in 307
      patients: a single-center, single-surgeon experience.
AB  - BACKGROUND: Matrix coils are based on Gugliemi detachable coils (GDC) but are
      covered with polyglycolic/polylactic acid. We present our experience regarding
      the immediate posttreatment results of aneurysm embolization using the 2 coil
      systems. PATIENTS: We embolized 219 aneurysms in 187 patients with the use of
      GDCs and 145 aneurysms in 120 patients with the use of Matrix coils. Age, sex
      distribution, unruptured aneurysm cases, and multiple aneurysm cases were similar
      in the 2 groups. The percentage of patients in severe clinical condition was
      significantly higher in the Matrix group. The mean aneurysm size was slightly
      larger in the GDC group but the mean neck size was larger in the Matrix group.
      RESULTS: Satisfactory occlusion (at least 90%) was achieved in 95.9% of GDC
      treated aneurysms and in 98.6% of Matrix-treated aneurysms. Procedure-related
      complications occurred in 19.6% of GDC procedures and in 15.6% of the Matrix ones
      resulting in procedure-related mortality and morbidity of 3.7% and 2.7% for the
      GDC group and 2.5% and 1.7% for the Matrix group. In the GDC group, outcome was
      good (modified Rankin Scale 0-2) in 92.6% of patients with unruptured aneurysms,
      in 82.6% of patients with Hunt and Hess grade I-III, and in 20.5% of those with
      Hunt and Hess grade of IV-V. The respective figures were 95%, 85.7%, and 22.7% in
      the Matrix group. CONCLUSION: In our series, Matrix coils have yielded slightly
      better results regarding satisfactory occlusion rate and clinical outcome but
      these differences are not statistically significant and probably reflect our
      increased experience in aneurysm embolization during the period we used Matrix
      coils.

PMID- 17032855
TI  - Embolization of experimental wide-necked aneurysms with iodine-containing
      polyvinyl alcohol solubilized in a low-angiotoxicity solvent.
AB  - BACKGROUND AND PURPOSE: To evaluate the ready-to-use iodine-containing polyvinyl
      alcohol (I-PVA) dissolved in the low angiotoxic solvent N-methyl pyrrolidone
      (NMP) for embolization of porcine wide-necked aneurysms. METHODS: Fourteen broad
      based carotid sidewall aneurysms were surgically constructed in 7 swine. I-PVA
      (40%) in NMP was injected under temporary balloon occlusion bridging the aneurysm
      neck. After 4 weeks, follow-up angiography, multisection CT angiography (MSCTA),
      and 3T MR imaging including MR angiography (MRA) sequences were performed.
      Afterward, harvested aneurysms were investigated histopathologically. RESULTS:
      The liquid embolic was well visible under fluoroscopy and displayed a favorable
      precipitation pattern, allowing for controlled polymer delivery. Ten aneurysms
      (71%) were initially completely occluded, whereas in 1 aneurysm, a minimal
      polymer leakage was observed. The other 4 aneurysms (29%) were almost completely
      occluded. One animal suffered a lethal rebleeding from the anastomosis after
      uneventful embolization. Aneurysms embolized with I-PVA could be discriminated
      well from the parent artery without beam-hardening artifacts on MSCTA, and no
      susceptibility artifacts were encountered on MR imaging. Histologic examination
      revealed all aneurysms covered with a membrane of fibroblasts and an endothelial
      cell layer while a moderate intraaneurysmal inflammatory response to the polymer
      was observed. CONCLUSION: I-PVA dissolved in NMP has proved its effectiveness for
      the embolization of experimental wide-necked aneurysms. This precipitating liquid
      embolic offers several interesting features in that it needs no preparation
      before use and no radiopaque admixtures, the latter allowing for artifact-free
      evaluation of treated aneurysms with MSCTA and MRA. Moreover, it uses NMP as a
      solvent, which has only a low angiotoxicity.

PMID- 17032856
TI  - Initial experience with the use of intravenous eptifibatide bolus during
      endovascular treatment of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Despite systemic heparinization, thromboembolic
      complications remain a major concern related to endovascular treatment of
      intracranial aneurysms. We assessed the safety of intravenous eptifibatide
      administered during aneurysm coiling procedures to prevent such complications.
      METHODS: From August 2001 to November 2004, 298 coil embolization procedures were
      performed to treat intracranial aneurysms; eptifibatide was used in 84
      endovascular coil embolization procedures to treat 79 aneurysms in 74 patients.
      We retrospectively reviewed medical charts, radiographic images, and procedure
      notes to evaluate periprocedural complications related to eptifibatide. RESULTS:
      The mean age of the 74 patients in our cohort was 55 +/- 9 years (range, 31-84)
      harboring 79 aneurysms (32 ruptured/47 unruptured). Eptifibatide was given
      prophylactically in 77 procedures, whereas in 7 procedures, it was given for
      treatment of a thromboembolic event (visualization of an arterial branch
      occlusion). A total of 5 (5.9% [total cohort]) bleeding complications related to
      eptifibatide occurred during 84 procedures. Two patients (2.4% [total
      cohort]/6.3% [ruptured group]) developed intracerebral hemorrhagic complications
      exacerbated by eptifibatide. The other 3 (3.6% [total cohort]) patients had groin
      hematomas requiring blood transfusions but had no surgical intervention. One
      thromboembolic event occurred in the 77 patients receiving eptifibatide
      prophylactically. CONCLUSIONS: Intravenous infusion of eptifibatide seems to be
      safe to administer in patients undergoing endovascular repair of an unruptured
      cerebral aneurysm. Caution must be used in patients harboring ruptured aneurysms
      as intracranial bleeding complications may occur. Further study is required to
      delineate the group of patients most likely to benefit from this therapy.

PMID- 17032857
TI  - Saccular aneurysms on straight and curved vessels are subject to different
      hemodynamics: implications of intravascular stenting.
AB  - Our aim was to examine hemodynamic implications of intravascular stenting in the
      canine venous pouch (sidewall or straight-vessel) and rabbit elastase (curved
      vessel) aneurysm models. Flow dynamics in stented (Wallstent) and nonstented
      versions were studied by using computational fluid dynamics simulations and in
      vitro flow visualization, with a focus on stent placement effects on aneurysmal
      flow stagnancy and flow impingement. Results show that sidewall and curved
      aneurysm models have fundamentally different hemodynamics (shear-driven versus
      inertia-driven) and thus stent placement outcomes.

PMID- 17032858
TI  - Focal increased cortical density in immediate postembolization CT scans of
      patients with intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Cortical hyperdensity was observed in the immediate
      postembolization CT scans of some patients with intracranial aneurysms following
      uneventful endovascular treatments. The clinical significance and possible
      underlying mechanism were evaluated. MATERIAL AND METHODS: Ninety-three
      consecutive patients with a total of 100 intracranial aneurysms, treated by
      endosaccular packing, were studied. Seventy-four aneurysms were treated with
      balloon assistance, and the remaining aneurysms were treated without balloon
      assistance. All patients underwent cranial CT just before and immediately after
      the endovascular treatment. If the post-treatment CT showed any new finding, an
      immediate MR imaging and a repeat CT 4-6 hours after the initial posttreatment CT
      were performed. Several parameters were investigated related to the presence of
      cortical hyperdensity. RESULTS: Cranial CT showed focal cortical hyperdensity
      following the treatment of 40/74 aneurysms (54%) with balloon remodeling and 9/26
      aneurysms (34.6%) without balloon assistance. None of these patients were
      symptomatic, and cortical hyperdensity resolved in the repeat CT scans. A
      statistically significant relationship was observed between the presence of this
      finding and the total amount of contrast material, microcatheter time, number of
      balloon inflations, and total balloon inflation time. CONCLUSION: Immediate
      postembolization CT may show focal cortical hyperdensity following uneventful
      endovascular aneurysm treatment, most likely caused by blood-brain barrier
      disruption resulting in accumulation of contrast medium. The hyperdensity was
      more frequent when balloon assistance was used but was also seen in the patients
      with no balloon use. It is important to differentiate this clinically
      insignificant finding from possible hemorrhage, which would affect patients'
      immediate postprocedural medical management.

PMID- 17032859
TI  - Dynamic CT perfusion imaging with acetazolamide challenge for evaluation of
      patients with unilateral cerebrovascular steno-occlusive disease.
AB  - BACKGROUND AND PURPOSE: Perfusion CT (PCT) has the ability to measure
      quantitative values and produce maps of cerebral blood flow (CBF), cerebral blood
      volume (CBV), and mean transit time (MTT). We assessed cerebral hemodynamics by
      using these parameters and acetazolamide challenge in patients with
      cerebrovascular steno-occlusive disease. METHODS: Fifteen patients underwent PCT
      with acetazolamide challenge. Comparison of mean CBF, CBV, and MTT was determined
      between hemispheres and before and after acetazolamide challenge. Hemispheric
      ratio and percent change due to acetazolamide administration were also
      calculated. Absolute values and percent changes 2 SDs outside the mean from the
      nonstenotic hemispheres were defined as abnormal. RESULTS: Significant decreases
      in CBF (-25.1%, P = .003) and significant increases in MTT (47.1%, P < .001) were
      found in stenotic hemispheres. After acetazolamide challenge, significant changes
      in CBF (-39.5%, P < .001) and MTT (92.9%, P < .001) were also seen. The
      acetazolamide test significantly decreased CBF hemispheric ratio (-20.3%, P <
      .001) and increased MTT hemispheric ratio (30.8%, P = .002), making both maps
      more asymmetric. Significance in CBF and MTT percent changes (P < .001 and P =
      .005, respectively) was found between hemispheres. When CBF percent changes were
      assumed to represent the true determinant of hemodynamic impairment, normal
      ranges of baseline MTT value and MTT percent changes demonstrated sensitivities
      of 66.7% and 100% and specificities of 58.3% and 75%, respectively, for detecting
      patients with hemodynamic impairment. CONCLUSION: Parameters obtained from PCT
      with acetazolamide are promising for the evaluation of cerebral hemodynamics in
      patients with cerebrovascular steno-occlusive disease.

PMID- 17032860
TI  - Intracranial angioplasty and stenting: long-term results from a single center.
AB  - BACKGROUND AND PURPOSE: Large-vessel intracranial atherosclerotic stenosis
      carries a proved stroke risk of 8%-22% per year with "best medical therapy." The
      long-term clinical neurologic and angiographic outcomes of angioplasty and/or
      stent placement for intracranial atherosclerosis in a consecutive series of
      patients are presented. METHODS: The demographics, procedural details, procedural
      outcome, and long-term neurologic follow-up in 60 consecutive patients with 71
      lesions, undergoing a total of 84 procedures, were analyzed. RESULTS: Angioplasty
      alone was performed in 62 procedures; 22 procedures involved stent placement. The
      periprocedural stroke+death rate was 4.8%. The overall complication-free success
      rate was 90.5%. Restenosis occurred in 23 lesions at a mean of 4.6 months; 13
      were re-treated without complication. There were 4 strokes and 4 non-neurologic
      deaths during 224 patient-years of follow-up. The annualized stroke rate was
      1.8%, and the annualized stroke+all-cause death rate was 3.0%. CONCLUSIONS: The
      stroke and death rates in this consecutive series of patients with severe
      intracranial atherosclerotic stenosis treated with optimal endovascular therapy
      are considerably less than those associated with the natural history of
      intracranial atherosclerosis treated with maximal medical therapy. Intracranial
      angioplasty with conditional stent placement is technically feasible and
      clinically effective with a substantial reduction in long-term stroke and death.

PMID- 17032861
TI  - Swine model of carotid artery atherosclerosis: experimental induction by surgical
      partial ligation and dietary hypercholesterolemia.
AB  - INTRODUCTION: Limited availability of a large animal model of carotid
      atherosclerosis has limited preclinical evaluation of endovascular therapeutic
      devices. The present study is aimed at developing such animal models with a novel
      approach, emphasizing the role of hemodynamics. METHODS: Using 18 carotid
      arteries from 9 miniswine, surgical partial ligation (approximately 80% stenosis)
      was carried out in untreated (group I; n = 6) and balloon-injured arteries (group
      II; n = 9). Three arteries were subjected to sham-operation for control (group
      III; n = 3). All animals were fed with a high-fat diet until sacrifice.
      Angiograms and histologic sections of the vessels were analyzed to evaluate both
      models. RESULTS: Atherosclerotic changes were confirmed in 6 of 6 in group I and
      6 of 9 arteries in group II, whereas all in group III remained intact. Three
      arteries in group II resulted in thrombotic occlusion. Advanced plaques with
      intraplaque hemorrhage and/or calcification were seen in 4 of 6 arteries in group
      I but none in group II. The cross-sectional area stenosis and atherosclerotic
      stage for plaques in group I were both significantly higher than that in groups
      II and III. CONCLUSION: In this series, surgical partial ligation with
      concomitant dietary hyperlipidemia is an appropriate experimental technique to
      develop advanced atherosclerotic plaques with minimal technical complications.
      This model showed no evidence of such benefits when applied in balloon-injured
      arteries.

PMID- 17032862
TI  - Organic solvents as vehicles for precipitating liquid embolics: a comparative
      angiotoxicity study with superselective injections of swine rete mirabile.
AB  - BACKGROUND AND PURPOSE: The organic solvent dimethyl-sulfoxide (DMSO), as a
      commonly used vehicle for nonadhesive liquid embolics, is not devoid of local
      angiotoxic effects. We compared microvascular toxicities of superselective
      infusions of DMSO with potentially more compatible solvents in swine rete
      mirabile. METHODS: Fourteen swine underwent angiography for superselective
      catheterization of 28 arteries of the rete while electrocardiography and intra
      arterial pressure were continuously monitored. The investigated solvents were
      DMSO, dimethyl isosorbide (DMI), ethyl lactate, glycofurol 75, N-methyl
      pyrrolidone (NMP), and solketal. Control infusion of saline ruled out catheter
      induced vasospasm in all cases. Each artery of the rete was infused only once
      with 0.8 mL of one of the solvents over 60 seconds. Acute angiographic and
      hemodynamic consequences were evaluated. Blood samples were assessed for signs of
      intravascular hemolysis. Brains and retia were harvested for gross and
      histopathologic investigation. RESULTS: On the basis of the angiographic data,
      DMSO induced the most pronounced vasospasm with the longest recovery period of
      all solvents investigated. Ethyl lactate, glycofurol 75, and solketal elicited
      less severe vasospasms and accordingly resolved much more quickly. DMI and NMP
      induced only minimal vasospasms with comparably short duration. No solvent caused
      significant hemodynamic alterations or hemolysis. Gross inspection of brains
      showed no abnormalities, whereas histopathologic examination revealed mostly
      nonspecific findings. One rete exposed to solketal displayed possible causal
      histotoxic changes. CONCLUSION: DMI and NMP produced far less vasospasm than
      DMSO. No changes in hemodynamic or hemolytic parameters and no histopathologic
      findings were observed with infusion of these solvents.

PMID- 17032863
TI  - Preoperative embolization of a cervicodorsal paraganglioma by direct percutaneous
      injection of onyx and endovascular delivery of particles.
AB  - We report the feasibility and efficacy of percutaneous injection of Onyx (Micro
      Therapeutics, Irvine, Calif.), a nonadhesive liquid embolic agent, into an
      unusually located paraganglioma, followed by endovascular embolization with
      particles before surgery.

PMID- 17032864
TI  - Preoperative embolization of cervical spine osteoblastomas: report of three
      cases.
AB  - Our aim was to describe the technique and clinical results of preoperative
      embolization of cervical spine osteoblastomas. We treated 3 patients with these
      tumors with transarterial embolization and subsequent surgical excision. In all 3
      patients, distal access to the tumor-supplying vessels was gained with a
      microcatheter and embolization was performed with polyvinyl alcohol particles. No
      complications occurred. Surgical resection was performed in all patients without
      relevant bleeding. The postoperative course was uneventful in all patients.
      Preoperative embolization is a valuable adjunct to the surgical treatment of
      osteoblastomas of the cervical spine.

PMID- 17032865
TI  - 2D time-of-flight MR venography in neonates: anatomy and pitfalls.
AB  - BACKGROUND AND PURPOSE: The dural venous sinuses in neonates differ from those in
      adults or older children in that the caliber of venous sinuses is smaller and
      there is skull molding. The aim of this retrospective study is to evaluate the
      presence of flow gaps in venous sinuses in neonates on 2D time-of-flight (TOF) MR
      venography (MRV). METHODS: Fifty-one neonates underwent coronal 2D TOF MRV. Nine
      also had CT venography (CTV) for comparison. In 1 neonate, a further 2D TOF MRV
      was performed in the sagittal plane; in another neonate, images were captured in
      the axial plane; and in another, a further coronal TOF MRV with shorter echo time
      was performed. RESULTS: Flow gap was seen in the posterior aspect of the superior
      sagittal sinus in 35 of 51 (69%). Focal narrowing of the superior sagittal sinus,
      in the region of convergence of lambdoid sutures, was detected in 7 of 51 (14%).
      The right and left transverse sinuses demonstrated flow gap in 13 of 51 (25%) and
      32 of 51 (63%) respectively. There was normal filling of contrast on CTV in the
      superior sagittal sinus, transverse sinus and sigmoid sinus in those cases with
      flow gap detected on coronal 2D TOF MRV. Right, left, and codominance of the
      transverse sinuses are as follows: 32 of 51 (63%), 5 of 51 (10%), and 14 of 51
      (27%), respectively. The right and left sigmoid sinuses demonstrated flow gap in
      7 of 51 (14%) and 8 of 51 (16%), respectively, and the left sigmoid sinus was
      absent in 1 of 51 (2%). CONCLUSION: The high proportion of flow gap in the venous
      sinuses of neonates, particularly of the superior sagittal sinus, could be
      attributed to the smaller caliber venous sinuses, slower venous flow, and skull
      molding.

PMID- 17032866
TI  - Acute necrotizing encephalopathy of childhood: correlation of MR findings and
      clinical outcome.
AB  - BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy
      of childhood (ANEC), an encephalopathy characterized by symmetrical involvement
      of the thalami, has historically been poor, but recent studies have reported
      better outcomes. By devising a MR imaging scoring system, we determined the
      relationship between characteristic MR findings and clinical outcome of patients
      with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively
      reviewed. A MR imaging score was calculated for each patient according to the
      presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of
      the patients was assessed, yielding outcome categories based on health state
      utility value. Spearman rank test was used to correlate the MR imaging score with
      clinical outcome of the patients. RESULTS: Statistically significant correlation
      (r = 0.76, P = .001) was found between the MR score and the outcome category. The
      thalami were involved in all 12 patients, brain stem in 10, cerebral white matter
      in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and
      cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients,
      and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a
      significant and positive correlation between the clinical outcome and the MR
      imaging score in patients with ANEC. The relation between clinical outcome and
      each individual MR feature remains to be determined. Patients with ANEC may have
      a better clinical outcome than has been previously reported.

PMID- 17032867
TI  - Persistent diffusion abnormalities in the brain stem of three children with
      mitochondrial diseases.
AB  - We report 2 children (patients 1 and 2) with Kearns-Sayre syndrome and 1 (patient
      3) with Leigh syndrome, who underwent serial diffusion-weighted MR imaging (DWI)
      studies for 2.8 (patient 1), 4.2 (patient 2), and 1.0 years (patient 3). The DWI
      revealed the persistent hyperintense signals in the pontine and mesencephalic
      tegmenta. The apparent diffusion coefficient in the affected regions remained
      constantly low, suggesting that cytotoxic edema and spongiform degenerations may
      compose these brain stem lesions.

PMID- 17032868
TI  - Dural arteriovenous malformation in a child with Bannayan-Riley-Ruvalcaba
      Syndrome.
AB  - Intracranial arteriovenous malformations (AVM) are a rare feature of Bannayan
      Riley-Ruvalcaba syndrome (BRRS). Palencia et al reported a case of intracranial
      arteriovenous malformation in a child with BRRS in a Spanish journal in 1986.
      However, the occurrence of dural AVM in a patient with BRRS has not since been
      addressed in the literature. Advancements in imaging and therapeutic
      embolization, and the ability now to screen for phosphatase and tensin homologue
      (PTEN) mutations allow us to detect and manage these patients sooner. Early
      detection of intracranial AVMs is necessary because of the risk for progression
      to venous ischemia and resultant neurologic damage. We present the case of a
      child with headaches and periorbital venous congestion due to a dural AVM with
      bilateral venous outflow occlusion who was treated with multiple embolizations,
      now with interval remission of headache symptoms.

PMID- 17032869
TI  - Diskography: infectious complications from a series of 12,634 cases.
AB  - BACKGROUND AND PURPOSE: Diskography is commonly performed to investigate pain of
      suspected diskogenic origin. Although uncommon, diskitis is a feared complication
      of this procedure. We reviewed the incidence of diskitis and other infectious
      complications following diskography in a large busy outpatient practice and
      discuss technical aspects that may contribute to infection prevention. METHODS:
      We reviewed the electronic records of all diskograms obtained at our institution
      during a 12.25-year period, looking for all cases of procedure-related infection.
      All diskograms had been obtained by skilled and experienced procedural
      radiologists in dedicated spine-injection suites with specialized technical
      staff. RESULTS: There were 12,634 examinations performed on 10,663 patients for a
      total of 37,135 disk levels. Of the disk levels, 5981 were cervical; 3083,
      thoracic; and 28,071, lumbar. Two cases of confirmed lumbar diskitis and no cases
      of either cervical or thoracic diskitis were seen in our series. No other
      infectious complications were found. The incidence of diskitis was 0.016% per
      examination and 0.0054% per disk level. CONCLUSION: In skilled and experienced
      hands using proper technique, diskography is a safe outpatient procedure with an
      extremely low incidence of diskitis and other procedure-related infections.

PMID- 17032870
TI  - The effects of cement volume on clinical outcomes of percutaneous vertebroplasty.
AB  - BACKGROUND AND PURPOSE: There exists significant variability in the volume of
      polymethylmethacrylate cement injected during percutaneous vertebroplasty. Larger
      cement volumes injected may be associated with better clinical outcomes, but
      larger volumes may also be associated with greater risk of complications related
      to cement leakage. We describe an analysis of the association between clinical
      and procedural variables, including cement volume injected, and the clinical
      outcomes of patients treated with single-level vertebroplasty. METHODS:
      Retrospective analysis of 158 patients treated with single-level vertebroplasty
      was performed. Relationships among patient and procedural variables and
      relationships between these variables and ordinal clinical outcome scores of pain
      and medication use at postprocedure time points from 1 week to 2 years were
      evaluated with bivariate and multivariable analyses. RESULTS: There was no
      significant association between the volume of cement injected and the clinical
      outcomes of postprocedure pain (P = .159-.871) and medication use (P = .223
      .875). CONCLUSION: Vertebroplasty operators need not feel compelled to achieve
      particular cement volumes injected in the pursuit of better clinical outcomes but
      should strive to achieve the maximal safe filling of individual vertebral bodies.

PMID- 17032871
TI  - Symptomatic refractures after vertebroplasty in patients with steroid-induced
      osteoporosis.
AB  - BACKGROUND AND PURPOSE: Refracture after percutaneous vertebroplasty in patients
      receiving oral glucocorticoid therapy has caused some patients and referring
      physicians to have negative perceptions concerning the efficacy of the initial
      vertebroplasty treatment. The purpose of this study was to analyze symptomatic
      refractures after vertebroplasty in patients on oral steroid therapy. We
      hypothesized that the higher refracture rate of patients on oral glucocorticoid
      therapy after percutaneous vertebroplasty is due not to an inadequacy of the
      procedure but rather to a naturally higher predisposition of these patients to
      refracture compared with patients with primary osteoporosis. METHODS: A
      retrospective analysis was performed on all osteoporosis patients having initial
      vertebroplasty from August 1999 to August 2003. The follow-up period was limited
      to 1 year after initial vertebroplasty session, with the last follow-up date
      ending in August 2004. Data were collected on 387 osteoporosis patients. RESULTS:
      Of the patients with primary osteoporosis, 20.6% patients refractured whereas
      37.8% of the patients with steroid-induced osteoporosis had symptomatic
      refractures within 1 year of initial vertebroplasty. Relative risk of refracture
      within 1 year for the patients with steroid-induced osteoporosis was 1.84
      compared with the patients with primary osteoporosis. In addition, the patients
      with steroid-induced osteoporosis were more likely to refracture after their
      second treatment session (within 1 year of initial vertebroplasty) than those
      with primary osteoporosis. CONCLUSION: Patients presenting on oral steroid
      therapy at their initial vertebroplasty are almost twice more likely to have
      symptomatic refractures than primary osteoporosis patients within 1 year of
      initial vertebroplasty.

PMID- 17032872
TI  - Lumbosacral nerve root avulsions: MR imaging demonstration of acute
      abnormalities.
AB  - Most of the previously reported lumbosacral nerve root avulsions presented with
      pseudomeningoceles at the time of delayed initial imaging. We report a case of
      traumatic lumbosacral nerve root injury associated with an isolated femur
      fracture and demonstrate the evolution of pseudomeningoceles following nerve root
      avulsions and edema in the perineural fat identified on the initial MR imaging.

PMID- 17032873
TI  - MR diffusion tensor imaging and fiber tracking in inflammatory diseases of the
      spinal cord.
AB  - PURPOSE: Our aim was to study the fractional anisotropy (FA) variations and the
      fiber tracking (FT) patterns observed in patients with myelitis. MATERIAL AND
      METHODS: Fifteen patients with symptomatic myelitis and 11 healthy subjects were
      prospectively selected. We performed T2-weighted and diffusion tensor imaging on
      a 1.5T MR scanner. FA and apparent diffusion coefficient maps were computed in
      both healthy subjects and patients. In each patient, we performed FT to study
      pathologic aspects on this imaging method. FA data were analyzed by using z
      scores. RESULTS: For the healthy subjects, averaged FA values ranged from 0.745
      to 0.751. All abnormal areas seen on T2-weighted imaging had a significantly
      decreased FA value. In 9 patients (60%), FA maps showed decreased FA areas,
      whereas T2-weighted imaging findings were normal. These areas matched the
      neurologic deficit in 33%. Eighty percent of patients had multiple decreased FA
      areas. Five patients (33%) had increased FA values in normal T2-weighted areas.
      CONCLUSION: We observed specific FA and FT pattern variations in patients with
      myelitis.

PMID- 17032874
TI  - A preliminary study of the effects of trigger timing on diffusion tensor imaging
      of the human spinal cord.
AB  - BACKGROUND AND PURPOSE: Diffusion tensor and diffusion-weighted spinal cord
      imaging remain relatively unexplored techniques despite demonstrations that such
      images can be obtained and may yield clinically relevant findings. In this study,
      we examined the temporal dynamics of spinal cord motion and their impact on
      diffusion tensor image quality. METHODS: Four healthy volunteers underwent phase
      contrast-based velocity mapping and segmented echo-planar diffusion tensor scans
      of the cervical spinal cord. Regions of interest in the cord were used to
      identify the temporal patterns of motion. The delay of data acquisition after the
      cardiac trigger was varied to correspond to either quiescence or motion of the
      cord. RESULTS: The cervical spinal cord consistently displayed maximal velocities
      in the range of 0.5 cm/s and accelerations of up to 25 cm/s(2). In both these
      respects, the cervical cord values were greater than those of the medulla.
      Despite this pronounced motion, approximately 40% of the cardiac cycle can be
      described as relatively calm, with absolute velocities and accelerations less
      than 20% of the maximum values. Confining image acquisition to this window
      reduced ghosting artifacts and increased the consistency with which the dominant
      direction of diffusion was along the rostral-caudal axis in both gray and white
      matter of the spine. Preliminary clinical application and fiber tracking in
      pathologic cases was feasible, and alterations of the diffusion properties by
      multiple sclerosis lesions, tumor, and syringomyelia were seen. CONCLUSIONS:
      Acquiring DTI data during the quiescent phase of spinal cord motion can reduce
      ghosting artifacts and improve fiber tracking.

PMID- 17032875
TI  - A nodular calcification of the alar ligament simulating a fracture in the
      craniovertebral junction.
AB  - We report a case of an incidental nodular calcification of the alar ligament
      simulating a fracture in the craniovertebral junction of a previously healthy 24
      year-old man. Three-dimensional CT and MR imaging revealed a 7.2 x 7.6 x 4.0 mm
      nodular calcification in the right alar ligament with normal adjacent bony
      structures. Serial cervical dynamic radiographs and open-mouth views showed that
      the cervical spine was stable without any change in the calcification.

PMID- 17032876
TI  - Not all age-related white matter hyperintensities are the same: a magnetization
      transfer imaging study.
AB  - PURPOSE: Our aim was to assess whether presumed histologic heterogeneity of age
      related white matter hyperintensities (WMH) is reflected in quantitative
      magnetization transfer imaging measures. MATERIALS AND METHODS: From a group of
      patients participating in a double-blind placebo-controlled multicenter study on
      the effect of pravastatin (PROSPER), we selected 56 subjects with WMH. WMH were
      classified as periventricular WMH (PVWMH) and deep WMH (DWMH). PVWMH were
      subclassified as irregular or smooth, depending on the aspect of their border.
      Signal intensity of WMH on T1-weighted images was scored as iso- or hypointense.
      The mean magnetization transfer ratio (MTR) value of different types of WMH was
      assessed and compared. As a control group, we selected 19 subjects with no or
      limited WMH. RESULTS: Mean (SE) MTR of PVWMH (frontal, 31.2% [0.2%]; occipital,
      32.2% [0.2%]) was lower than that of DWMH (33.7% [0.5%]). The mean MTR of frontal
      PVWMH (31.2% [0.2%]) was lower than that of occipital PVWMH (32.2% [0.2%]).
      Compared with occipital PVWMH, frontal PVWMH more often had a smooth lining (72%
      frontal versus 8% occipital) and an area with low signal intensity on T1-weighted
      images (76% frontal versus 35% occipital). MTR did not differ between smooth
      (31.1% [0.3%]) and irregular (31.6% [0.5%]) PVWMH. CONCLUSION: Age-related WMH
      are heterogeneous, despite their similar appearance on T2-weighted images. By
      taking into account heterogeneity of age-related WMH, both in terms of etiology
      and in terms of severity of tissue destruction, one may obtain better
      understanding on the causes and consequences of these lesions.

PMID- 17032877
TI  - Improved delineation of glioma margins and regions of infiltration with the use
      of diffusion tensor imaging: an image-guided biopsy study.
AB  - BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of
      treatment for malignant gliomas, is limited by our inability to accurately
      determine tumor margins. As a result, despite recent advances, the prognosis
      remains appalling. Because gliomas preferentially infiltrate along white matter
      tracks, methods that show white matter disruption should improve this
      delineation. In this study, results of histologic examination from samples
      obtained from image-guided brain biopsies were correlated with diffusion tensor
      images. METHODS: Twenty patients requiring image-guided biopsies for presumed
      gliomas were imaged preoperatively. Patients underwent image-guided biopsies with
      multiple biopsies taken along a single track that went into normal-appearing
      brain. Regions of interest were determined from the sites of the biopsies, and
      diffusion tensor imaging findings were compared with glioma histology. RESULTS:
      Using diffusion tissue signatures, it was possible to differentiate gross tumor
      (reduction of the anisotropic component, q > 12% from contralateral region), from
      tumor infiltration (increase in the isotropic component, p > 10% from
      contralateral region). This technique has a sensitivity of 98% and specificity of
      81%. T2-weighted abnormalities failed to identify the margin in half of all
      specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor
      margin in gliomas. Such techniques can improve the delineation of the radiation
      therapy target volume for gliomas and potentially can direct local therapies for
      tumor infiltration.

PMID- 17032878
TI  - Comparing perfusion metrics obtained from a single compartment versus
      pharmacokinetic modeling methods using dynamic susceptibility contrast-enhanced
      perfusion MR imaging with glioma grade.
AB  - BACKGROUND AND PURPOSE: Numerous different parameters measured by perfusion MR
      imaging can be used for characterizing gliomas. Parameters derived from 3
      different analyses were correlated with histopathologically confirmed grade in
      gliomas to determine which parameters best predict tumor grade. METHODS: Seventy
      four patients with gliomas underwent dynamic susceptibility contrast-enhanced MR
      imaging (DSC MR imaging). Data were analyzed by 3 different algorithms. Analysis
      1 estimated relative cerebral blood volume (rCBV) by using a single compartment
      model. Analysis 2 estimated fractional plasma volume (V(p)) and vascular transfer
      constant (K(trans)) by using a 2-compartment pharmacokinetic model. Analysis 3
      estimated absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and
      mean transit time (MTT) by using a single compartment model and an automated
      arterial input function. The Mann-Whitney U test was used make pairwise
      comparisons. Binary logistic regression was used to assess whether rCBV, V(p),
      K(trans), CBV, CBF, and MTT can discriminate high- from low-grade tumors.
      RESULTS: rCBV was the best discriminator of tumor grade ype, followed by CBF,
      CBV, and K(trans). Spearman rank correlation factors were the following: rCBV =
      0.812 (P < .0001), CBF = 0.677 (P < .0001), CBV = 0.604 (P < .0001), K(trans) =
      0.457 (P < .0001), V(p) = 0.301 (P =.009), and MTT = 0.089 (P = .448). rCBV was
      the best single predictor, and K(trans) with rCBV was the best set of predictors
      of high-grade glioma. CONCLUSION: rCBV, CBF, CBV K(trans), and V(p) measurements
      correlated well with histopathologic grade. rCBV was the best predictor of glioma
      grade, and the combination of rCBV with K(trans) was the best set of metrics to
      predict glioma grade.

PMID- 17032879
TI  - Transient splenial lesion of the corpus callosum in clinically mild influenza
      associated encephalitis/encephalopathy.
AB  - BACKGROUND: Reversible lesions in the splenium of the corpus callosum (SCC),
      caused by various agents such as influenza, rotavirus, Escherichia coli, mumps,
      and adenovirus, were previously defined in a handful of cases. We present 5 cases
      with transient diffusion restriction of the SCC associated with influenza A virus
      infection. MATERIALS AND METHODS: Five patients with influenza-associated
      encephalitis/encephalopathy and sudden-onset neurologic symptoms following a
      prodromal flulike episode were examined by MR and diffusion-weighted imaging
      (DWI). RESULTS: Three patients, who had drowsiness and new-onset convulsions,
      recovered spontaneously without any medication. In the other 2 seizure-free
      patients, 1 had trigeminal neuralgia and headache and the other had facial
      numbness and left upper monoparesis. All patients had round well-defined ovoid
      hyperintense splenial lesions (14.94 +/- 1.87 mm) on DWI with a significantly low
      apparent diffusion coefficient (ADC) of 0.41 +/- 0.05 x 10(-3) mm(2)/s compared
      with 0.84 +/- 0.01 x 10(-3) mm(2)/s of normal-appearing white matter. In the
      patient with a motor deficit, additional lesions were found in the cerebral deep
      white matter. The high signal intensity of the splenial and deep white matter
      lesions on DWI completely disappeared on follow-up studies, and ADC values also
      improved, returning to those of normal-appearing white matter on days 8-11.
      Clinically, all patients completely recovered on days 4-9. CONCLUSION: A
      transient lesion of the SCC is a significant but nonspecific finding. It is
      probably due to edematous and/or inflammatory changes of the SCC. It may be the
      only detectable change in patients with good prognosis, indicating a clinically
      mild form of encephalitis/encephalopathy.

PMID- 17032880
TI  - Higher prevalence of cortical lesions observed in patients with acute stroke
      using high-resolution diffusion-weighted imaging.
AB  - Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30
      seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR],
      256 seconds) having increased spatial resolution and signal to noise and
      decreased eddy current artifact in 42 patients with acute ischemic stroke. Total
      lesion volumes were similar; however, twice as many lesions were identified on
      DWI-HR, predominately in cortical gray matter. Modest improvements to imaging
      resulted in increased conspicuity, potentially affecting diagnosis, suspected
      pathogenic mechanism, and therapeutic decision.

PMID- 17032881
TI  - Reversed discrepancy between CT and diffusion-weighted MR imaging in acute
      ischemic stroke.
AB  - PURPOSE: We sought to determine whether an early CT ischemic lesion showing
      parenchymal hypoattenuation might be undetectable on diffusion-weighted imaging
      (DWI) in acute cerebral ischemia. MATERIALS AND METHODS: We retrospectively
      evaluated CT and MR images of 70 consecutive patients with acute middle cerebral
      artery (MCA) infarction. All patients underwent CT and MR imaging within 6 hours
      of symptom onset. We determined the presence of reversed discrepancy (RD),
      defined as an early ischemic lesion showing parenchymal hypoattenuation on CT but
      no hyperintensity on DWI. CT Hounsfield units (HU), apparent diffusion
      coefficients (ADCs), and perfusion parameters were calculated for RD lesions.
      RESULTS: RD was found in 9 (12.9%) patients and at basal ganglia (89%). The mean
      HU of RD lesion was lower than that of normal tissue (DeltaHU, 2.33 +/- 0.74, P <
      .001). RD lesions showed no significant decrease of ADC (ADC ratio, 0.97 +/-
      0.07, P = .059) and cerebral blood flow (relative CBF, 0.87 +/- 0.20, P > 0.05).
      Delayed DWI hyperintensity occurred in 8 (88.8%) RD lesions, and all lesions
      progressed to infarction. In 6 (66%) of 9 patients with RD, Alberto Stroke
      Program Early CT scores of ischemic lesions were lower on CT than those on DWI.
      CONCLUSION: RD was uncommonly found mainly in basal ganglia, and all RD lesions
      progressed to infarction at follow-up. Early CT ischemic lesion showing
      parenchymal hypoattenuation may be undetectable on DWI, and DWI may underestimate
      extent of severe ischemic tissue in patients with acute MCA infarction.

PMID- 17032882
TI  - Calcified cerebral emboli.
AB  - Intracranial calcifications may represent calcified cerebral emboli. Calcified
      emboli may be overlooked even though cerebral CT is widely used as a stroke
      assessment. We report 4 cases of calcified cerebral emboli and demonstrate the
      value of CT in the diagnosis and temporal evaluation of such emboli.

PMID- 17032884
TI  - Normal-appearing white matter changes vary with distance to lesions in multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) disease processes in normal
      appearing white matter (NAWM) may be different close to MR-visible lesions than
      farther from these lesions. We aimed to investigate the relationship of NAWM
      changes to the distance to the lesions. METHODS: We measured B(1)-corrected T1
      and magnetization transfer ratio (MTR) maps in 63 patients with MS (11 primary
      progressive, 34 relapsing-remitting, 18 secondary progressive). We used histogram
      analyses to assess the global properties of lesions, of 4 consecutive 1-mm pixel
      layers of NAWM around the lesions, and of distant NAWM located at least 4-mm from
      lesions in all directions. In 22 healthy controls, we measured white matter MTR
      and T1 histograms. Histogram parameters were statistically analyzed by using a
      linear mixed model. RESULTS: The first and second NAWM pixel layers around the
      lesions had a significantly lower MTR histogram peak position than distant NAWM,
      whereas T1 histogram peak position was similar between all types of NAWM.
      Furthermore, MTR histograms of distant NAWM were statistically indistinguishable
      from those of control white matter, whereas T1 histograms of distant NAWM had
      significantly decreased peak height for relapsing-remitting MS and secondary
      progressive MS and significantly increased peak position for secondary
      progressive MS. CONCLUSION: Our results may suggest that axonal damage and
      demyelination in NAWM mainly arise as a secondary result of visible lesions, with
      the largest effect close to these lesions. NAWM disease farther from the lesions
      may be mainly characterized by subtle blood-brain barrier damage, with leakage of
      fibrinogen into the parenchyma and microplaque formation, processes that are
      detected with T1 but not with MTR.

PMID- 17032883
TI  - Diffusion anisotropy changes in the brains of professional boxers.
AB  - BACKGROUND AND PURPOSE: Professional boxing may result in brain injury. We
      hypothesize that quantitative MR diffusion imaging may be useful in determining
      early white matter changes. METHODS: Forty-nine professional boxers (age 30 +/-
      4.5 years) and 19 healthy control subjects (age 32 +/- 9.5 years) were imaged on
      a clinical 1.5T scanner. None of the subjects had neurologic disorder or deficit.
      The average diffusion constant (D(av)) and diffusion anisotropy (FA) were
      determined pixel by pixel. Regional diffusion measurements were done in the
      corpus callosum (CC) and internal capsule (IC). The whole brain diffusion
      constant (BD(av)) was also determined. Student t test was used to analyze the
      diffusion difference between boxers and the healthy control subjects. P < .05 was
      considered statistically significant. RESULTS: Of the 49 professional boxers, 42
      had normal conventional MRIs. The remaining 7 boxers had abnormal MR imaging
      findings dominated by nonspecific white matter disease. There was a significant
      difference in diffusion and anisotropy measurements in all the boxers compared
      with the healthy control subjects. In the boxer group, BD(av) increased and FA
      decreased significantly in the CC and posterior limb of IC. The measured FA and
      D(av) inversely correlated in regions of CC and IC in boxers but not in healthy
      control subjects. BD(av) also robustly correlated with both FA and D(av) in the
      splenium of CC in boxers. CONCLUSION: Increased BD(av) and the decreased FA in
      the CC and IC may represent preclinical signs of subtle brain injury in
      professional boxers.

PMID- 17032885
TI  - A rare anatomic variant of a solitary internal carotid artery associated with
      moyamoya phenomenon of the middle cerebral artery.
AB  - A case of a congenital solitary internal carotid artery with complicated
      anastomosis is presented. This rare anomaly was an incidental finding at cerebral
      angiography in a patient with a poor-grade subarachnoid hemorrhage and a ruptured
      anterior communicating artery aneurysm.

PMID- 17032887
TI  - Modeling the impact of adjuvant therapy and screening mammography on U.S. breast
      cancer mortality between 1975 and 2000: introduction to the problem.

PMID- 17032888
TI  - Dissemination of adjuvant multiagent chemotherapy and tamoxifen for breast cancer
      in the United States using estrogen receptor information: 1975-1999.
AB  - BACKGROUND: Clinical trials have shown tamoxifen to be effective only in women
      with estrogen receptor (ER)-positive tumors. In a previous model, trends in the
      utilization of adjuvant therapy were modeled only as a function of age and stage
      of the disease and not ER status. In this paper, we integrate this previous
      estimate on the use of adjuvant systemic therapy for breast cancer in the United
      States with information on ER status from the Patterns of Care (POC) data to
      estimate the dissemination of adjuvant therapy for women with different ER-status
      tumors. We also summarize efficacy of adjuvant systemic therapy reported in the
      overviews of early breast cancer clinical trials. These two inputs, dissemination
      and efficacy, are key pieces for models that investigate the effect of breast
      cancer adjuvant therapy on the decline of U.S. breast cancer mortality. METHODS:
      The adjustments to the previous models are calculated using the POC data on 7116
      women with breast cancer diagnosed from 1987 to 1991 and in 1995 who were
      randomly selected from the Surveillance, and Epidemiology, and End Results (SEER)
      program registries. The POC data provide more accurate information on treatment
      and clinical variables (e.g., ER status) than the SEER data because medical
      records are reabstracted and further verified with treating physicians. RESULTS:
      Use of multiagent chemotherapy is higher for younger women (<50 years) and for
      women whose tumors were shown to be ER negative or borderline. The use of
      tamoxifen is higher among older women and women with ER-positive tumors. After
      1980 the combined use of multiagent chemotherapy and tamoxifen for women
      diagnosed with breast cancer at ages 69 or younger increased more for women whose
      tumors were ER status positive or unknown than ER status negative. Older women
      (>69 years) seem to receive almost exclusively tamoxifen irrespective of ER
      status, except for a small percentage of those with more advanced stages (II- and
      II+/IIIA) who also receive multiagent chemotherapy. DISCUSSION: The estimated
      dissemination trends by ER status, based on modeling the POC data, reveal that
      treatment strategies with demonstrated efficacy in clinical trials have been
      adopted into practice. The dissemination and efficacy are the two factors
      necessary to input into models to determine the population impact of these
      therapies on U.S. breast cancer mortality. The largest decline in mortality would
      be expected for younger women (<60 years) with ER-positive tumors or whose tumors
      are of unknown status because of the largest efficacy and dissemination of
      adjuvant therapy in this group.

PMID- 17032889
TI  - Competing risks to breast cancer mortality.
AB  - BACKGROUND: Simulation models analyzing the impact of treatment interventions and
      screening on the level of breast cancer mortality require an input of mortality
      from causes other than breast cancer, or competing risks. METHODS: This chapter
      presents an actuarial method of creating cohort life tables using published data
      that removes breast cancer as a cause of death. RESULTS: Mortality from causes
      other than breast cancer as a percentage of all-cause mortality is smallest for
      women in their forties and fifties, as small as 85% of the all-cause rate,
      although the level and percentage of the impact varies by birth cohort.
      CONCLUSION: This method produces life tables by birth cohort and by age that are
      easily included as a common input by the various CISNET modeling groups to
      predict mortality from other causes. Attention to removing breast cancer
      mortality from all-cause mortality is worthwhile, because breast cancer mortality
      can be as high as 15% at some ages.

PMID- 17032890
TI  - Changing patterns in breast cancer incidence trends.
AB  - Incidence rates for breast cancer in U.S. women have steadily increased for
      decades, but the reasons are not well understood. A recent upturn in these trends
      suggests that one component may be the effect of more aggressive screening in the
      population. The age-period-cohort framework, in which the temporal components
      associated with year of diagnosis and generation are evaluated, can assist in
      interpreting the elements associated with these trends. A unique approach for
      exploring other ways of partitioning the contribution of the different temporal
      components is described and applied to breast cancer incidence data (ICDO 174.0
      174.9) from the Surveillance, Epidemiology and End Results (SEER) registries.
      Single-year intervals for age and year of diagnosis were used to fit models that
      provide estimates of the trends associated with the individual temporal elements.
      A log-linear model for age, period, and cohort was fitted using Poisson
      regression, and estimates of the separate time trends were calculated. The trends
      with period increased after 1982, when more aggressive screening began, and the
      trend is steeper for women older than 40 years. Cohort trends have increased
      steadily, although recent cohorts appear to be somewhat flat for women aged 50
      years or younger, whereas the trend for those older than 50 years have continued
      to increase. Estimates of cohort trends in rates are also provided by
      extrapolating what would have occurred had there been no period trend before or
      after 1982, thus providing an estimate of the magnitude of the upturn that
      occurred after the recent emphasis on screening.

PMID- 17032891
TI  - Additional common inputs for analyzing impact of adjuvant therapy and mammography
      on U.S. mortality.
AB  - In estimating the impact of mammography and adjuvant treatment on U.S. breast
      cancer mortality rates, several parameters were common to all the Cancer
      Intervention and Surveillance Modeling Network (CISNET) models participating in
      the breast cancer base case. Models either used the parameters directly as input
      or calibrated their models to reproduce the common set of parameters. This
      chapter describes the common input parameters that are not specifically discussed
      elsewhere in the monograph.

PMID- 17032892
TI  - Modeling the impact of treatment and screening on U.S. breast cancer mortality: a
      Bayesian approach.
AB  - BACKGROUND: Breast cancer mortality (BCM) in the United States declined from 33.1
      per 100,000 women in 1990 to 26.6 per 100,000 women in 2000, yielding a 19.6%
      relative decline in BCM since 1990. Our goal is to apportion this decline between
      screening and therapy and to be able to state with some certainty that these
      interventions affected this decline. METHODS: We started with an age-appropriate
      population of 2,000,000 women in 1975 and monitored these women through 2000. On
      the basis of population data each year, we assigned screening and breast cancer
      to women. If a woman was diagnosed with breast cancer, we simulated a lifetime
      for her with death from breast cancer, and we modified this lifetime depending on
      the use of adjuvant therapy and whether the cancer was screen-detected. A woman's
      lifetime was taken as the minimum of her lifetime with death from breast cancer
      and her simulated natural lifetime. We used Bayesian simulation modeling, which
      allows for associating probability distributions with our estimates. RESULTS: We
      calculated the probabilities that screening mammography and adjuvant therapy
      contributed to the observed decline in BCM to be 90% and 99%, respectively. The
      posterior mean reduction in BCM due to screening is 10.6% +/- 5.7% and due to
      therapy is 19.5% +/- 5.4%. The decrease in the hazard of BCM due to tamoxifen use
      for ER-positive tumors is 37% +/- 14% and that due to adjuvant (nontaxane)
      chemotherapy is 15% +/- 14%. DISCUSSION: The spread in our posterior
      distributions reflect the uncertainty present in the data sources available to
      us. However, despite this uncertainty we conclude a high probability that both
      screening and improvements in therapy contributed to the reduction in BCM
      observed in the United States from 1990 to 2000.

PMID- 17032893
TI  - The Wisconsin Breast Cancer Epidemiology Simulation Model.
AB  - The Wisconsin Breast Cancer Epidemiology Simulation Model is a discrete-event,
      stochastic simulation model using a systems-science modeling approach to
      replicate breast cancer incidence and mortality in the U.S. population from 1975
      to 2000. Four interacting processes are modeled over time: (1) natural history of
      breast cancer, (2) breast cancer detection, (3) breast cancer treatment, and (4)
      competing cause mortality. These components form a complex interacting system
      simulating the lives of 2.95 million women (approximately 1/50 the U.S.
      population) from 1950 to 2000 in 6-month cycles. After a "burn in" of 25 years to
      stabilize prevalent occult cancers, the model outputs age-specific incidence
      rates by stage and age-specific mortality rates from 1975 to 2000. The model
      simulates occult as well as detected disease at the individual level and can be
      used to address "What if?" questions about effectiveness of screening and
      treatment protocols, as well as to estimate benefits to women of specific ages
      and screening histories.

PMID- 17032894
TI  - The SPECTRUM population model of the impact of screening and treatment on U.S.
      breast cancer trends from 1975 to 2000: principles and practice of the model
      methods.
AB  - OBJECTIVE: This stochastic simulation model was developed to estimate the impact
      of screening and treatment diffusion on U.S. breast cancer mortality between 1975
      and 2000. MODELING APPROACH: We use an event-driven continuous-time state
      transition model. Women who are destined to develop breast cancer may be screen
      detected, present with symptoms, or die of other causes before cancer is
      diagnosed. At presentation, the cancer has a stage assigned on the basis of mode
      of detection. Cancers are assumed to be estrogen receptor (ER) positive or
      negative. Data on screening and treatment diffusion are based on national
      datasets; other parameters are based on a synthesis of the evidence available in
      the literature. MODEL METHODS: The model is calibrated to predict incidence and
      stage distribution (in situ, local, regional, and distant). Other than screening
      or treatment, background events that affect mortality are not explicitly modeled
      but are captured in the deviation between model projections of mortality trends
      and actual trends. We assume that: 1) tumors progress more slowly in older age
      groups, 2) screen- and clinically detected disease have the same survival
      conditional on age and stage, 3) women do not die of breast cancer within the
      "lead time" period, 4) screening benefits are captured by shifts in stage at
      diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical
      sojourn time and dwell times in each of the clinical stages are stochastically
      independent. MODEL RESULTS: Dissemination of screening and therapeutic advances
      had a substantial impact on mortality trends. We estimate that, by the year 2000,
      diffusion of screening lowered mortality by 12.4% and treatment improvements and
      dissemination lowered mortality by 14.6%. CONCLUSIONS: Models such as this one
      can be useful to translate clinical trial findings to general populations. This
      model can also be used inform policy debates about how to best achieve targeted
      reductions in breast cancer morbidity and mortality.

PMID- 17032895
TI  - The MISCAN-Fadia continuous tumor growth model for breast cancer.
AB  - The MISCAN-Fadia model was used to analyze the impact of screening and adjuvant
      treatment on U.S. breast cancer mortality between 1975 and 2000. MISCAN-Fadia
      uses the concept of "fatal diameter" to model survival and screening benefit and
      is based on continuous tumor growth. It consists of four major components:
      population, natural history, screening, and treatment. Population parameters were
      quantified using U.S. population data. Most natural history and screening
      parameters were fitted to the Swedish Two County screening trial data; some were
      based on Surveillance, Epidemiology, and End Results data. Adjuvant treatment
      parameters were quantified using data from the Early Breast Cancer Trialists'
      Collaborative Group's meta-analysis. The simulated trend in incidence matches the
      observed trend reasonably well; the simulated mortality is equal to the observed
      in 1975 but becomes increasingly too high in 2000. We estimate that screening
      leads to a 15% and adjuvant treatment to a 21% mortality reduction in the year
      2000.

PMID- 17032896
TI  - The University of Rochester model of breast cancer detection and survival.
AB  - This paper presents a biologically motivated model of breast cancer development
      and detection allowing for arbitrary screening schedules and the effects of
      clinical covariates recorded at the time of diagnosis on posttreatment survival.
      Biologically meaningful parameters of the model are estimated by the method of
      maximum likelihood from the data on age and tumor size at detection that resulted
      from two randomized trials known as the Canadian National Breast Screening
      Studies. When properly calibrated, the model provides a good description of the
      U.S. national trends in breast cancer incidence and mortality. The model was
      validated by predicting some quantitative characteristics obtained from the
      Surveillance, Epidemiology, and End Results data. In particular, the model
      provides an excellent prediction of the size-specific age-adjusted incidence of
      invasive breast cancer as a function of calendar time for 1975-1999. Predictive
      properties of the model are also illustrated with an application to the dynamics
      of age-specific incidence and stage-specific age-adjusted incidence over 1975
      1999.

PMID- 17032897
TI  - A stochastic model for predicting the mortality of breast cancer.
AB  - Consider a cohort of women, identified by year of birth, some of whom will
      eventually be diagnosed with breast cancer. A stochastic model is developed for
      predicting the U.S. breast cancer mortality that depends on advances in therapy
      and dissemination of mammographic screening. The predicted mortality can be
      compared with the same cohort having usual care with no screening program and
      absence of modern therapy, or a cohort in which only a proportion participate in
      a screening program and have modern therapy. The model envisions that a woman may
      be in four health states: i.e., 1) no disease or breast cancer that cannot be
      diagnosed (S0), 2) preclinical state (Sp), 3) clinical state (Sc), and 4) disease
      specific death (Sd). The preclinical disease refers to breast cancer that is
      asymptomatic but that may be diagnosed with a special exam. The clinical state
      refers to symptomatic disease diagnosed under usual care. One of the basic
      assumptions of the model is that the disease is progressive; i.e., the
      transitions for the first three states are S0-->Sp-->Sc. The other basic
      assumption is that any reduction in mortality associated with earlier diagnosis
      is due to a stage shift in diagnosis; i.e., early diagnosis results in a larger
      proportion of earlier stage patients. The model is used to predict changes in
      female breast cancer mortality in the U.S. women for 1975-2000. The model is
      general and may predict mortality for other chronic diseases that satisfy the two
      basic assumptions.

PMID- 17032899
TI  - A comparative review of CISNET breast models used to analyze U.S. breast cancer
      incidence and mortality trends.
AB  - The CISNET Breast Cancer program is a National Cancer Institute-sponsored
      collaboration composed of seven research groups that have modeled the impact of
      screening and adjuvant treatment on trends in breast cancer incidence and
      mortality over the period 1975-2000 (base case). This collaboration created a
      unique opportunity to make direct comparison of results from different models of
      population-based cancer screening produced in response to the same question.
      Comparing results in all but the most cursory way necessitates comparison of the
      models themselves. Previous chapters have discussed the models individual in
      detail. This chapter will aid the reader in understanding key areas of difference
      between the models. A focused analysis of differences and similarities between
      the models is presented with special attention paid to areas deemed most likely
      to contribute substantially to the results of the target analysis.

PMID- 17032898
TI  - A stochastic simulation model of U.S. breast cancer mortality trends from 1975 to
      2000.
AB  - BACKGROUND: We present a simulation model that predicts U.S. breast cancer
      mortality trends from 1975 to 2000 and quantifies the impact of screening
      mammography and adjuvant therapy on these trends. This model was developed within
      the Cancer Intervention and Surveillance Network (CISNET) consortium. METHOD: A
      Monte Carlo simulation is developed to generate the life history of individual
      breast cancer patients by using CISNET base case inputs that describe the secular
      trend in breast cancer risk, dissemination patterns for screening mammography and
      adjuvant treatment, and death from causes other than breast cancer. The model
      generates the patient's age, tumor size and stage at detection, mode of
      detection, age at death, and cause of death (breast cancer versus other) based in
      part on assumptions on the natural history of breast cancer. Outcomes from
      multiple birth cohorts are summarized in terms of breast cancer mortality rates
      by calendar year. RESULT: Predicted breast cancer mortality rates follow the
      general shape of U.S. breast cancer mortality rates from 1975 to 1995 but level
      off after 1995 as opposed to following an observed decline. Sensitivity analysis
      revealed that the impact adjuvant treatment may be underestimated given the lack
      of data on temporal variation in treatment efficacy. CONCLUSION: We developed a
      simulation model that uses CISNET base case inputs and closely, but not exactly,
      reproduces U.S. breast cancer mortality rates. Screening mammography and adjuvant
      therapy are shown to have both contributed to a decline in U.S. breast cancer
      mortality.

PMID- 17032900
TI  - Impact of mammography on U.S. breast cancer mortality, 1975-2000: are
      intermediate outcome measures informative?
AB  - Seven models have estimated the contribution of screening to the decrease in U.S.
      breast cancer mortality between 1975 and 2000. We will investigate whether the
      model estimates of the mortality reduction due to screening are associated with
      intermediate outcome measures (IOMs). Detection rates at screening, 1- and 2-year
      sensitivity, program sensitivity, and incidence of advanced tumors are used as
      IOMs. Moreover, the model parameters preclinical duration and sensitivity are
      analyzed. The correlation of IOMs with mortality is assessed for actual U.S.
      screening and for an intensive screening scenario, with annual screening at ages
      40-79 years with 100% participation. Also, 12 alternative screening scenarios are
      run for one of the models, and within-model correlation between IOMs and
      mortality reduction is described. Resulting correlations between IOMs and
      mortality reduction are mostly weak. For 2-year sensitivity and the incidence of
      advanced tumors, correlations are high in the intensive screening scenario.
      Within-model correlations are strong for incidence of advanced tumors and program
      sensitivity. Intermediate outcome measures have limited potential in predicting
      the impact of mammographic screening on mortality. Incidence of advanced tumors
      and program sensitivity are measures that merit further consideration as
      surrogates for mortality reduction.

PMID- 17032901
TI  - Impact of adjuvant therapy and mammography on U.S. mortality from 1975 to 2000:
      comparison of mortality results from the cisnet breast cancer base case analysis.
AB  - The CISNET breast cancer program is a consortium of seven research groups
      modeling the impact of various cancer interventions on the national trends of
      breast cancer incidence and mortality. Each of the modeling groups participated
      in a CISNET breast cancer base case analysis with the objective of assessing the
      impact of mammography and adjuvant therapy on breast cancer mortality between
      1975 and 2000. The comparative modeling approach used to address this question
      allowed for a unique view into the process of modeling. Results shown here expand
      on those recently reported in the New England Journal of Medicine (Berry et al.,
      N Engl J Med 2005;353:1784-92) by presenting mortality impact in several
      different ways to facilitate comparisons between models. Comparisons of each
      group's results in the context of modeling assumptions made during the process
      gave insight into how specific model assumptions may have affected the results.
      The median estimate for the percent decline in breast cancer mortality due to
      mammography was 15% (range of 8%-23%), and the median estimate for the percent
      decline in mortality due to adjuvant treatment was 19% (range of 12%-21%). A
      detailed discussion of the differences in modeling approaches and how those
      differences may have influenced the mortality results concludes the chapter.

PMID- 17032902
TI  - Modeling cancer natural history, epidemiology, and control: reflections on the
      CISNET breast group experience.

PMID- 17032903
TI  - Amino acid residues in the P2X7 receptor that mediate differential sensitivity to
      ATP and BzATP.
AB  - Agonist properties of the P2X7 receptor (P2X7R) differ strikingly from other P2X
      receptors in two main ways: high concentrations of ATP (> 100 microM) are
      required to activate the receptor, and the ATP analog 2',3'-O-(4-benzoyl
      benzoyl)ATP (BzATP) is both more potent than ATP and evokes a higher maximum
      current. However, there are striking species differences in these properties. We
      sought to exploit the large differences in ATP and BzATP responses between rat
      and mouse P2X7R to delineate regions or specific residues that may be responsible
      for the unique actions of these agonists at the P2X7R. We measured membrane
      currents in response to ATP and BzATP at wild-type rat and mouse P2X7R, at
      chimeric P2X7Rs, and at mouse P2X7Rs bearing point mutations. Wild-type rat P2X7R
      was 10 times more sensitive to ATP and 100 times more sensitive to BzATP than
      wild-type mouse P2X7R. We found that agonist EC50 values were determined solely
      by the ectodomain of the P2X7R. Two segments (residues 115-136 and 282-288), when
      transposed together, converted mouse sensitivities to those of rat. Point
      mutations through these regions revealed a single residue, asparagine284, in the
      rat P2X7R that fully accounted for the 10-fold difference in ATP sensitivity,
      whereas the 100-fold difference in BzATP sensitivity required the transfer of
      both Lys127 and Asn284 from rat to mouse. Thus, single amino acid differences
      between species can account for large changes in agonist effectiveness and
      differentiate between the two widely used agonists at P2X7 receptors.

PMID- 17032904
TI  - The effect of low pH on breast cancer resistance protein (ABCG2)-mediated
      transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic
      acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models.
AB  - Some cellular uptake systems for (anti)folates function optimally at acidic pH.
      We have tested whether this also applies to efflux from cells by breast cancer
      resistance protein (BCRP; ABCG2), which has been reported to transport folic
      acid, methotrexate, and methotrexate di- and triglutamate at physiological pH.
      Using Spodoptera frugiperda-BCRP membrane vesicles, we showed that the ATP
      dependent vesicular transport of 1 muM methotrexate by BCRP is 5-fold higher at
      pH 5.5 than at physiological pH. The transport of methotrexate was saturable at
      pH 5.5, with apparent Km and Vmax values of 1.3 +/- 0.2 mM and 44 +/- 2.5 nmol/mg
      of protein/min, respectively, but was linear with drug concentration at pH 7.3 up
      to 6 mM methotrexate. In contrast to recent reports, we did not detect transport
      of methotrexate diglutamate at physiological pH, but we did find transport at pH
      5.5. We also found that 7-hydroxy-methotrexate, the major metabolite of
      methotrexate, is transported by BCRP both at physiological pH and (more
      efficiently) at low pH. The pH effect was also observed in intact BCRP
      overexpressing cells: we found a 3-fold higher level of resistance to both
      methotrexate and the prototypical BCRP substrate mitoxantrone at pH 6.5 as at
      physiological pH. Furthermore, with MDCKII-BCRP monolayers, we found that
      resveratrol, which is a neutral compound at pH < or = 7.4, is efficiently
      transported by BCRP at pH 6.0, whereas we did not detect active transport at pH
      7.4. We conclude that BCRP transports substrate drugs more efficiently at low pH,
      independent of the dissociation status of the substrate.

PMID- 17032905
TI  - Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent
      reduction in norepinephrine transporter surface expression linked to changes in
      syntaxin 1A/transporter complexes.
AB  - Norepinephrine (NE) transporters (NETs) are high-affinity transport proteins that
      mediate the synaptic clearance of NE after vesicular release. NETs represent a
      major therapeutic target for antidepressants and are targets of multiple
      psychostimulants including amphetamine (AMPH) and cocaine. Recently, we
      demonstrated that syntaxin 1A (SYN1A) regulates NET surface expression and,
      through binding to the transporter's NH(2) terminus, regulates transporter
      catalytic function. AMPH induces NE efflux and may also regulate transporter
      trafficking. We monitored NET distribution and function in catecholaminergic cell
      lines (CAD) stably transfected with either full-length human NET (CAD-hNET) or
      with an hNET N-terminal deletion (CAD-hNETDelta(28-47) cells). In hNET-CAD cells,
      AMPH causes a slow and small reduction of surface hNET with a modest increase in
      hNET/SYN1A associations at the plasma membrane. In contrast, in CAD-hNETDelta(28
      47) cells, AMPH induces a rapid and substantial reduction in surface hNETDelta(28
      47) accompanied by a large increase in plasma membrane hNETDelta(28-47)/SYN1A
      complexes. We also found that AMPH in CAD-hNETDelta(28-47) cells induces a robust
      increase in cytosolic Ca2+ and concomitant activation of calcium/calmodulin
      dependent protein kinase II (CaMKII). Inhibition of either the increase in
      intracellular Ca2+ or CaMKII activity blocks AMPH-stimulated hNETDelta(28-47)
      trafficking and the formation of hNETDelta(28-47)/SYN1A complexes. Here, we
      demonstrate that AMPH stimulation of CAMKII stabilizes an hNET/SYN1A complex.
      This hNET/SYN1A complex rapidly redistributes, upon AMPH treatment, when
      mechanisms supported by the transporter's NH2 terminus are eliminated.

PMID- 17032906
TI  - Impact of residence on prevalence and intensity of prescription drug use among
      older adults.
AB  - BACKGROUND: Higher levels of morbidity among older adults result in greater need
      for pharmaceutical products and pharmacy services compared with the need in the
      general population. Rural residents reportedly have reduced access to healthcare
      services secondary to transportation difficulties, a limited supply of healthcare
      workers and facilities, and financial constraints. OBJECTIVE: To examine
      differences in the prevalence and intensity of prescription pharmaceutical use
      among urban and rural older adults in Manitoba, Canada. METHODS: Participant data
      from the 1996/1997 Manitoba Study of Health and Aging were linked to
      pharmaceutical claims data recorded in Manitoba Health's Drug Program Information
      Network. The effect of residence on the prevalence and intensity of drug use was
      determined, in addition to the effects of other sociodemographic characteristics,
      measures of health, and health service utilization. RESULTS: The prevalence of
      prescription pharmaceutical use did not differ between urban and rural residents
      (90.6% vs 89.5%, respectively; p = 0.60). Users of home-care services (OR 1.93;
      95% CI 1.09 to 3.39), those who perceived their income as adequate (2.38; 95% CI
      1.09 to 5.17), and those with a higher number of chronic health problems (1.42;
      95% CI 1.26 to 1.62) were significantly more likely to access prescription
      medications. Rural and urban residents were equally likely to be high users of
      prescription drugs (21.3% vs 20.0%, respectively; p = 0.64). CONCLUSIONS: Poor
      health status is associated with a higher prevalence and intensity of use of
      prescription drugs among older Manitobans. Rural residence is not a barrier to
      receipt of prescription pharmaceuticals.

PMID- 17032907
TI  - Acute renal failure associated with vancomycin- and tobramycin-laden cement in
      total hip arthroplasty.
AB  - OBJECTIVE: To describe 2 cases of acute renal failure (ARF) associated with the
      use of antibiotic-laden cement incorporated in total hip arthroplasties (THA).
      CASE SUMMARIES: An 82-year-old female received a right THA with antibiotic-laden
      cement spacers. She developed ARF 5 months following implantation, concurrent
      with an elevated serum tobramycin concentration of 5.5 microg/mL. After
      explantation of the prosthesis and spacers, serum creatinine and antibiotic
      concentrations decreased to within normal limits. A 79-year-old male received
      antibiotic-laden cement spacers in a revision of his right THA due to infection.
      ARF developed 1 1/2 months after the revision; a serum tobramycin concentration
      was 2.9 microg/mL. Serum creatinine and antibiotic serum concentrations decreased
      to within normal limits with explantation. DISCUSSION: More than 250 000 joint
      replacements are performed yearly in the US. A common complication is infection,
      which occurs in 1-2% of primary replacements and 3-4% of revisions of previously
      infected prostheses. Antibiotic-laden cement is used for prosthesis placement to
      prevent or treat infection, while minimizing systemic drug exposure. Both
      patients described here received antibiotic-laden spacers during THA and
      subsequently developed ARF in conjunction with elevated serum tobramycin
      concentrations. Use of the Naranjo probability scale and consideration of
      possible contributing factors suggest a probable association of the antibiotic
      laden cement and the development of ARF in these patients. CONCLUSIONS:
      Antibiotic-laden cement with aminoglycosides and/or vancomycin has the potential
      for systemic toxicity and should be used according to guidelines and with
      increased vigilance and prudent monitoring in patients at increased risk for
      nephrotoxicity.

PMID- 17032908
TI  - Pulmonary abnormalities in immunocompromised patients: comparative detection with
      parallel acquisition MR imaging and thin-section helical CT.
AB  - PURPOSE: To compare parallel acquisition magnetic resonance (MR) imaging with
      thin-section helical computed tomography (CT) for depiction of pulmonary
      abnormalities suggestive of pneumonia in immunocompromised patients. MATERIALS
      AND METHODS: The institutional review board approved this study; prior consent
      was obtained. Thirty consecutive neutropenic patients (10 women, 20 men; mean
      age, 51 years +/- 15 [standard deviation]; range, 25-75 years) with fever of
      unknown origin or clinical signs and symptoms of lung infection were examined
      with breath-hold single-shot half-Fourier turbo spin-echo MR imaging. To reduce
      image blurring and increase MR signal in the lungs, the echo time was shortened
      with generalized autocalibrating partially parallel acquisition (GRAPPA).
      Patients underwent thoracic CT (four detector rows and 1-mm section thickness [4
      x 1 mm]; pitch, 6) as reference standard. Pulmonary abnormalities (ill-defined
      nodules, ground-glass opacity areas, and consolidation), their location and
      distribution, and lesion characteristics were analyzed at MR imaging by three
      readers, blinded to results of CT, in consensus. Frequencies were calculated for
      each feature; paired Wilcoxon rank sum test was used to examine whether
      differences between CT and MR imaging features were statistically significant
      (alpha < .05). Bonferroni adjustments were performed. Overall sensitivity,
      specificity, and positive and negative predictive values were determined.
      RESULTS: Twenty-two patients had pulmonary abnormalities at CT. In 21 (95%)
      patients, pneumonia was correctly diagnosed with MR imaging. One false-negative
      finding occurred in a patient with ill-defined nodules smaller than 1 cm at CT.
      One false-positive finding with MR imaging was the result of blurring and
      respiratory artifacts (sensitivity, 95%; specificity, 88%; positive predictive
      value, 95%; negative predictive value, 88%). There was no significant difference
      in lesion location and distribution. CONCLUSION: With parallel imaging (GRAPPA
      technique) and fast MR imaging, detection of pulmonary abnormalities is almost as
      good as with CT. MR imaging has a slight disadvantage in its lower capability to
      assist in characterization of specific internal features, such as cavitations.

PMID- 17032909
TI  - Multidetector CT in abdominal aortic aneurysm treated with endovascular repair:
      are unenhanced and delayed phase enhanced images effective for endoleak
      detection?
AB  - PURPOSE: To retrospectively determine the sensitivity and specificity of
      unenhanced, delayed enhanced phase (DEP), and arterial enhanced phase (AEP) multi
      detector row computed tomography (CT) for depicting endoleaks during follow-up of
      endovascular aneurysm repair. MATERIALS AND METHODS: Fifty patients (two women,
      48 men; mean age, 72 years) underwent follow-up multi-detector row CT 1, 6, and
      12 months after endovascular aneurysm repair. Unenhanced CT was performed with
      2.5-mm collimation; 1-mm collimation was used with AEP and DEP examinations. Two
      independent readers assessed the presence of endoleak in three reading sessions:
      AEP (session A), unenhanced and AEP (session B), and AEP and DEP (session C). At
      6- and 12-month follow-up, a fourth set was included: 1-month unenhanced and AEP
      (session D). Sensitivity, specificity, and positive predictive value of each
      session were calculated. Triple-phase multi-detector row CT was the reference
      standard. RESULTS: At 1 month, sensitivity, specificity, and positive predictive
      value, respectively, were 79%, 75%, and 55% for session A; 93%, 97%, and 93% for
      session B; and 93%, 78%, and 62% for session C. At 6 months, sensitivity,
      specificity, and positive predictive value, respectively, were 92%, 68%, and 48%
      for session A; 92%, 100%, and 100% for session B; and 100%, 84%, and 67% for
      session C. At 12 months, sensitivity, specificity, and positive predictive value,
      respectively, were 80%, 80%, and 50% for session A; 90%, 98%, and 90% for session
      B; and 100%, 80%, and 56% for session C. Sensitivity did not significantly differ
      (P > .05) among reading sessions A, B, and C, whereas specificity and positive
      predictive values in session B were significantly higher (P < .001). For 6- and
      12-month follow-up, no significant differences (P > .05) were found between
      sessions D and B. CONCLUSION: The combination of AEP and unenhanced imaging
      performed at 1-month follow-up offers improved specificity and positive
      predictive values compared with AEP alone. DEP imaging does not significantly
      increase sensitivity for detection of endoleaks, but it does depict low-flow
      endoleaks not seen at AEP.

PMID- 17032910
TI  - Malignant astrocytic tumors: clinical importance of apparent diffusion
      coefficient in prediction of grade and prognosis.
AB  - PURPOSE: To retrospectively assess the apparent diffusion coefficient (ADC) for
      prediction of malignancy and prognosis of malignant astrocytic tumors. MATERIALS
      AND METHODS: The institutional review board approved this study and did not
      require patient informed consent. Findings from 37 consecutive patients (21 men,
      16 women; mean age, 43 years) with pathologically proved malignant astrocytic
      tumors that included 22 glioblastomas (GBMs) and 15 anaplastic astrocytomas (AAs)
      were retrospectively evaluated. The minimum ADC value of each tumor was
      preoperatively determined from several regions of interest defined in the tumor,
      preferably with avoidance of cystic or necrotic components, on ADC maps derived
      from isotropic diffusion-weighted images. Surgical intervention, followed by
      radiation therapy, was undertaken in all cases according to hospital protocol.
      Immunohistologically, Ki-67 labeling index (LI), indicating cell proliferation,
      was also determined. The patients were classified into two groups, progressive
      and stable, according to the 2-year observation after the initial treatment.
      Correlation analysis (Pearson product moment correlation), Student t test, Welch
      test, receiver operating characteristic analysis, and Kaplan-Meier method with
      log-rank test were used for statistical evaluation. RESULTS: There was a
      significant negative correlation between minimum ADC and Ki-67 LI (r = -0.562, P
      < .001). The mean minimum ADC (0.834 x 10(-3) mm2 x sec(-1)) of GBM was
      significantly lower than that (1.06 x 10(-3) mm2 x sec(-1)) of AA (P < .001,
      Student t test). The mean minimum ADC (0.80 x 10(-3) mm2 x sec(-1)) of the
      progressive group was significantly lower than that (1.037 x 10(-3) mm2 x sec(
      1)) of the stable group (P < .001). The cutoff value of 0.90 x 10(-3) mm2 x sec(
      1) for minimum ADC for differentiation of patients with a favorable prognosis
      from those with a poor prognosis provided the best combination of sensitivity
      (79%) and specificity (81%) (receiver operating characteristic analysis). The
      significant difference in the prognosis between two groups classified by using
      this cutoff value of minimum ADC was noted (P = .002, log-rank test). CONCLUSION:
      The minimum ADC of malignant astrocytomas can provide additional information
      about their clinical malignancy related to posttreatment prognosis.

PMID- 17032911
TI  - Active Crohn disease: CT findings and interobserver agreement for enteric phase
      CT enterography.
AB  - PURPOSE: To retrospectively evaluate small-bowel enhancement characteristics and
      the sensitivity, specificity, and interobserver agreement of computed tomographic
      (CT) findings by using histologic and endoscopic results as a reference standard
      in patients undergoing enteric phase CT enterography. MATERIALS AND METHODS: The
      institutional review board approved this retrospective HIPAA-compliant study,
      which included patients who consented to having their medical records used for
      research purposes. Enteric phase CT enterographic and ileoscopic findings with or
      without ileal histologic results were examined in 42 patients (24 women, 18 men).
      Enteric phase CT enterography was performed after 150 mL of intravenous contrast
      material was administered at 4 mL/sec, with a 45-second delay. Mural attenuation
      was measured in the distended and collapsed jejunal and ileal loops and in the
      terminal ileum. Two radiologists examined CT images for findings of Crohn
      disease. Mural attenuation for different bowel loops was compared by using a
      Student t test, with kappa statistics used to measure interobserver agreement and
      Pearson correleation coefficients used to compare visual and quantitative
      measures. RESULTS: Distended jejunal loops had significantly greater attenuation
      than distended ileal loops (113 HU vs 72 HU; P < .001). Attenuation of collapsed
      jejunal (134 HU) and ileal (108 HU) loops was greater than that of distended
      jejunal and ileal loops (P < .001). Terminal ileal enhancement was the most
      sensitive visual CT finding of Crohn disease for both radiologists. Mural
      thickening demonstrated the greatest interobserver agreement (kappa = 0.83).
      Visual enhancement and quantitative mural attenuation were significantly
      correlated (P < .003). CONCLUSION: At enteric phase CT enterography, jejunal
      attenuation is greater than ileal attenuation and collapsed bowel loops
      demonstrate greater attenuation than distended bowel loops. Mural
      hyperenhancement and increased mural thickness are the most sensitive CT findings
      of active Crohn disease.

PMID- 17032912
TI  - Phyllodes tumor of the breast: correlation between MR findings and histologic
      grade.
AB  - PURPOSE: To retrospectively evaluate the magnetic resonance (MR) imaging findings
      of phyllodes tumor of the breast and to compare these findings with the
      histologic grade. MATERIALS AND METHODS: Institutional review board approval and
      informed consent were obtained. The authors reviewed the MR findings in 30 female
      patients aged 16-73 years (mean, 40.2 years) with surgically confirmed phyllodes
      tumors. Analyzed MR findings included tumor shape, margin, internal enhancement,
      and size; signal intensity (SI) of tumor higher than that of normal breast tissue
      on T1-weighted images; SI of tumor lower than or equal to that of normal tissue
      on T2-weighted images; cyst wall appearance; kinetic curve assessment; and
      apparent diffusion coefficient (ADC). The MR findings and histologic grade were
      statistically analyzed to determine whether any correlations existed. Significant
      MR findings were compared with histopathologic findings. RESULTS: Nineteen
      benign, six intermediate (characterized by five to nine cell reproductions at 10
      high-power fields, pushing or infiltrative margins, moderate stromal cellularity,
      and atypia and overgrowth), and five malignant phyllodes tumors were assessed.
      Irregular cyst wall (P = .003), tumor SI lower than or equal to normal tissue SI
      on T2-weighted images (P = .005), and low ADC (P = .001) correlated significantly
      with histologic grade. Tumor SI higher than normal tissue SI on T1-weighted
      images was more frequent in the malignant (in three of five tumors) and
      intermediate (in three of six tumors) groups than in the benign group (in two of
      19 tumors); however, it was not a significant finding (P = .024). Tumor SI higher
      than normal tissue SI on T1-weighted images and irregular cyst wall corresponded
      histopathologically to hemorrhagic infarction and necrosis, respectively. Tumor
      SI lower than or equal to normal tissue SI on T2-weighted images and low ADC
      corresponded histopathologically to stromal hypercellularity. Other findings were
      not significant. CONCLUSION: Several MR findings can be used to help determine
      the histologic grade of phyllodes breast tumors.

PMID- 17032913
TI  - Cervical lymph node metastases: MR imaging of gadofluorine M and monocrystalline
      iron oxide nanoparticle-47 in a rabbit model of head and neck cancer.
AB  - PURPOSE: To prospectively compare the accuracy of gadofluorine M with that of
      monocrystalline iron oxide nanoparticle (MION)-47 for the depiction of cervical
      lymph node metastases at magnetic resonance (MR) imaging in a rabbit model of
      head and neck cancer by using histologic analysis as the reference standard.
      MATERIALS AND METHODS: Experiments were approved by the animal care committee.
      VX2 carcinomas were implanted in both ears of 11 rabbits 4 weeks before MR
      imaging. T2-weighted, T2*-weighted, and T1-weighted MR images were acquired, and
      sequential T1-weighted MR imaging was performed immediately and 30 minutes after
      administration of gadofluorine M (0.05 mmol gadolinium per kilogram body weight).
      T2-weighted and T2*-weighted MR imaging were performed 24 hours after
      administration of MION-47 (2.6 mg iron per kilogram body weight). Gadofluorine M-
      and MION-47-enhanced MR imaging were performed separately and independently by
      two radiologists who had no knowledge of histopathologic results, and the
      presence of metastases in lymph nodes was evaluated. A receiver operating
      characteristic analysis was conducted to compare the diagnostic value of
      gadofluorine M- and MION-47-enhanced MR imaging. RESULTS: Metastases were
      confirmed in 20 of 77 lymph nodes at histopathologic analysis. The area under the
      curve was significantly greater for gadofluorine M-enhanced MR imaging (0.997 and
      0.981 for readers 1 and 2, respectively) than for MION-47-enhanced MR imaging
      (0.889 and 0.846 for readers 1 and 2, respectively). For gadofluorine M-enhanced
      MR imaging, sensitivity was 100% for both readers and specificity was 89.5% for
      reader 1 and 87.7% for reader 2. For MION-47-enhanced MR imaging, sensitivity was
      80.0% for both readers and specificity was 75.4% for reader 1 and 71.9% for
      reader 2. CONCLUSION: Gadofluorine M-enhanced MR imaging has higher accuracy for
      depicting lymph node metastases than does MION-47-enhanced MR imaging.

PMID- 17032914
TI  - High-spatial-resolution multistation MR angiography with parallel imaging and
      blood pool contrast agent: initial experience.
AB  - The purpose of this study was to prospectively evaluate the diagnostic accuracy
      of reader detection of 75% or greater stenosis at high-spatial-resolution
      multistation magnetic resonance (MR) angiography performed with matrix coils and
      a blood pool contrast agent. Ten healthy volunteers and 10 patients were
      examined. All participants provided informed consent to participate in this
      institutional review board-approved study. For contrast agent-enhanced
      multistation MR angiography, an albumin-binding gadolinium chelate, gadofosveset
      trisodium, was used. Imaging was performed during the first-pass and steady-state
      phases of the contrast agent. Vessel conspicuity on the first-pass MR angiograms
      obtained in both volunteers and patients was rated as excellent for 93% of
      vessels. At steady-state imaging, vessel conspicuity was rated as excellent or
      good for 89% of vessels. Gadofosveset trisodium-enhanced MR angiography yielded
      sensitivities of 100% and 97% and specificities of 96% and 97% for detection of
      significant disease in the carotid and lower extremity arteries, respectively.

PMID- 17032915
TI  - Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) is the most common cause of poor long
      term outcomes after allogeneic bone marrow transplantation (BMT), but the
      pathophysiology of chronic GVHD still remains poorly understood. We tested the
      hypothesis that the impaired thymic negative selection of the recipients will
      permit the emergence of pathogenic T cells that cause chronic GVHD. Lethally
      irradiated C3H/HeN (H-2k) recipients were reconstituted with T-cell-depleted bone
      marrow cells from major histocompatibility complex [MHC] class II-deficient (H2
      Ab1-/-) B6 (H-2b) mice. These mice developed diseases that showed all of the
      clinical and histopathological features of human chronic GVHD. Thymectomy
      prevented chronic GVHD, thus confirming the causal association of the thymus.
      CD4+ T cells isolated from chronic GVHD mice were primarily donor reactive, and
      adoptive transfer of CD4+ T cells generated in these mice caused chronic GVHD in
      C3H/HeN mice in the presence of B6-derived antigen-presenting cells. Our results
      demonstrate for the first time that T cells that escape from negative thymic
      selection could cause chronic GVHD after allogeneic BMT. These results also
      suggest that self-reactivity of donor T cells plays a role in this chronic GVHD,
      and improvement in the thymic function may have a potential to decrease chronic
      GVHD.

PMID- 17032916
TI  - New agents that stimulate erythropoiesis.
AB  - Recombinant human erythropoietin (rhEpo) has proven to be remarkably safe and
      effective for treatment of anemias, primarily those secondary to renal disease
      and malignancy. Despite the worldwide use of rhEpo, concerns about its cost, the
      need for frequent parenteral administration, and the development of anti-Epo
      antibodies have prompted development of improved agents to stimulate
      erythropoiesis. Three strategies appear to be particularly promising. The half
      life of Epo in the circulation can be prolonged by the addition of N-linked
      carbohydrate groups, by formation of adducts with polyethylene glycol, and by
      preparation of Epo multimers. Second, mimetic peptides can effectively trigger
      signal transduction at the Epo receptor, thereby boosting red-cell production.
      Finally, the hypoxia inducible transcription factor (HIF) can be
      pharmacologically induced by oral agents, resulting in enhanced expression not
      only of endogenous Epo but also of other genes important in the regulation of
      erythropoiesis.

PMID- 17032917
TI  - MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth
      muscle cell migration.
AB  - Transforming growth factor-beta (TGF-beta) and its signaling mediators play
      crucial roles in vascular formation. Our previous microarray analysis identified
      monocyte chemoattractant protein-1 (MCP-1) as a TGF-beta target gene in
      endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic
      effect of TGF-beta by recruiting vascular smooth muscle cells (VSMCs) and
      mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we
      show that TGF-beta promotes the formation of new blood vessels and this promotion
      is attenuated when MCP-1 activity is blocked by its neutralizing antibody. Wound
      healing and transwell assays established that MCP-1 functions as a
      chemoattractant to stimulate migration of VSMCs and mesenchymal 10T1/2 cells
      toward ECs. Furthermore, the conditioned media from TGF-beta-treated ECs
      stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-beta
      induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene
      target of TGF-beta via Smad3/4. Taken together, our findings suggest that MCP-1
      mediates TGF-beta-stimulated angiogenesis by enhancing migration of mural cells
      toward ECs and thus promoting the maturation of new blood vessels.

PMID- 17032918
TI  - GSK-3 mediates differentiation and activation of proinflammatory dendritic cells.
AB  - The key components of the intracellular molecular network required for the
      expression of a specific function of dendritic cells (DCs) are as yet undefined.
      Using an in vitro model of human monocyte-derived DC differentiation, this study
      investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional
      enzyme critical for cellular differentiation, apoptosis, self-renewal, and
      motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage
      development during differentiation of DCs, (2) is constitutively active in
      immature DCs and suppresses spontaneous maturation, and (3) acquires a
      proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF
      alpha secretion, and partially inhibits IL-10 in the context of DC activation. In
      particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of
      the proinflammatory cytokine IL-12p70 by integrating the activities of other
      kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may
      therefore act as a key integrator of activating and inhibitory pathways involved
      in proinflammatory DC differentiation and activation.

PMID- 17032919
TI  - Plasminogen activator inhibitor type 1 is protective during severe Gram-negative
      pneumonia.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) levels are consistently elevated
      in patients with severe pneumonia and sepsis and highly predictive for an
      unfavorable outcome. In addition, pneumonia is associated with strongly elevated
      PAI-1 levels in the pulmonary compartment. However, whether PAI-1 causally
      affects antibacterial host defense in vivo remains unknown. We report here that
      pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae is
      associated with local production of PAI-1 in the lungs of wild-type mice. PAI-1
      deficiency impaired host defense as reflected by enhanced lethality and increased
      bacterial growth and dissemination in mice with a targeted deletion of the PAI-1
      gene. Conversely, transgenic overexpression of PAI-1 in the lung using a
      replication-defective adenoviral vector markedly improved host defense against
      Klebsiella pneumonia and sepsis. PAI-1 deficiency reduced accumulation of
      neutrophils in the lungs during pneumonia, whereas PAI-1 overexpression in
      healthy lungs resulted in neutrophil influx, suggesting that PAI-1 protects the
      host against Klebsiella pneumonia by promoting neutrophil recruitment to the
      pulmonary compartment. These data demonstrate for the first time that PAI-1 is
      essential for host defense against severe Gram-negative pneumonia.

PMID- 17032920
TI  - VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor
      metastasis to distant sites.
AB  - The mechanisms by which tumors metastasize to sentinel and distant lymph nodes,
      and beyond, are poorly understood. We developed transgenic mice that overexpress
      vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein
      specifically in the skin and studied the effects of chemically-induced skin
      carcinogenesis in this model. We found that in contrast to VEGF-A, VEGF-C does
      not increase the growth of primary tumors, but instead induces expansion of
      lymphatic networks within sentinel lymph nodes, even before the onset of
      metastasis. Once the metastatic cells arrived at the sentinel lymph nodes, the
      extent of lymphangiogenesis at these sites increased. Of importance, in mice with
      metastasis-containing sentinel lymph nodes, tumors that expressed VEGF-C were
      more likely to metastasize to additional organs, such as distal lymph nodes and
      lungs. No metastases were observed in distant organs in the absence of lymph node
      metastases. These findings indicate an important role of VEGF-C-induced lymph
      node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel
      lymph nodes. VEGF-C is therefore a good target to slow or even prevent the onset
      of metastasis.

PMID- 17032921
TI  - Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC
      UKALL12/ECOG 2993 study.
AB  - Most adults with acute lymphoblastic leukemia (ALL) who achieve complete
      remission (CR) will relapse. We examined the outcome of 609 adults with recurring
      ALL, all of whom were previously treated on the Medical Research Council (MRC)
      UKALL12/ECOG2993 study, where the overall survival (OS) of newly diagnosed
      patients is 38% (95% confidence interval [CI]=36%-41%) at 5 years. By contrast,
      OS at 5 years after relapse was 7% (95% CI=4%-9%). Factors predicting a good
      outcome after salvage therapy were young age (OS of 12% in patients younger than
      20 years vs OS of 3% in patients older than 50 years; 2P<.001) and short duration
      of first remission (CR1) (OS of 11% in those with a CR1 of more than 2 years
      versus OS of 5% in those with a CR1 of less than 2 years; 2P<.001). Treatment
      received in CR1 did not influence outcome after relapse. In a very highly
      selected subgroup of patients who were able to receive HSCT after relapse, some
      were long-term survivors. We conclude from a large, unselected series with mature
      follow-up that most adults with recurring ALL, whatever their prior treatment,
      cannot be rescued using currently available therapies. Prevention of recurrence
      is the best strategy for long-term survival in this disease.

PMID- 17032922
TI  - PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells.
AB  - The effect and mode of action of the protein kinase C (PKC) inhibitor PKC412 on
      human multiple myeloma (MM) cell lines (HMCLs) and primary MM cells was explored.
      We found that PKC412 induced apoptosis of HMCLs and primary MM cells with
      variable efficacy; however, some activity was seen against all HMCLs and primary
      MM cells with at least 0.5 microM PKC412. PARP cleavage and decreased PKC
      activity was observed in all HMCLs tested. Furthermore, PKC412 inhibited C-FOS
      transcription and nuclear protein expression, induced reactive oxygen species
      (ROS) production, and induced both sustained C-JUN expression and
      phosphorylation. The latter was inhibited by cotreatment with the JNK inhibitor
      SP600125, which similarly abrogated PKC412-induced apoptosis, suggesting that
      PKC412-induced apoptosis is a JNK-dependent event. PKC412 treatment secondarily
      induced prosurvival stress responses as evidenced by activation of NFkappaB and
      increased expression of the heat shock proteins HSP70 and HSP90. Consistent with
      the former, sequential inhibition of NFkappaB activation with bortezomib or SN50
      synergistically enhanced cell killing. Our results demonstrate that PKC412
      induces JNK-dependent apoptosis of HMCLs and primary MM cells and that this
      effect is enhanced by NFkappaB inhibition. The further evaluation of PKC412 in
      the treatment of MM is justified.

PMID- 17032923
TI  - Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts
      for studying megakaryocyte and platelet function in vivo.
AB  - To generate transgenic mice that express Cre-recombinase exclusively in the
      megakaryocytic lineage, we modified a mouse bacterial artificial chromosome (BAC)
      clone by homologous recombination and replaced the first exon of the platelet
      factor 4 (Pf4), also called CXCL4, with a codon-improved Cre cDNA. Several
      strains expressing the transgene were obtained and one strain, Q3, was studied in
      detail. Crossing Q3 mice with the ROSA26-lacZ reporter strain showed that Cre
      recombinase activity was confined to megakaryocytes. These results were further
      verified by crossing the Q3 mice with a strain containing loxP-flanked integrin
      beta1. Excision of this conditional allele in megakaryocytes was complete at the
      DNA level, and platelets were virtually devoid of the integrin beta1 protein. The
      Pf4-Cre transgenic strain will be a valuable tool to study megakaryopoiesis,
      platelet formation, and platelet function.

PMID- 17032925
TI  - Humoral immune response and immunoglobulin G Fc receptor genotype are associated
      with better clinical outcome following idiotype vaccination in follicular
      lymphoma patients regardless of their response to induction chemotherapy.
AB  - We have reported that anti-idiotype antibody response and FcgammaRIIIa 158
      valine/valine (V/V) genotype both correlate with better outcome in a group of 136
      follicular lymphoma patients receiving idiotype vaccination after induction
      chemotherapy. Here, we examined whether this correlation is related in any way to
      the chemotherapy response. In patients with complete response (CR), the 5-year
      progression-free survival (PFS) was 69% for patients with antibody response
      and/or V/V genotype, while the PFS was only 40% for patients with neither; the
      median time to progression (TTP) was 10.47 versus 3.46 years (P=.012). In
      patients with partial response (PR), the 5-year PFS was 57% for patients with
      antibody response and/or V/V genotype, and 17% for patients with neither; the
      median TTP was not reached versus 1.31 years (P=.001). This study further
      confirms the strong association of clinical outcome with antibody response and
      with the functionally more active form of the Fc receptor in patients receiving
      idiotype vaccination regardless of their response to induction chemotherapy.

PMID- 17032924
TI  - Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM).
AB  - Second mitochondria-derived activator of caspases (Smac) promotes apoptosis via
      activation of caspases. Here we show that a low-molecular-weight Smac mimetic
      LBW242 induces apoptosis in multiple myeloma (MM) cells resistant to conventional
      and bortezomib therapies. Examination of purified patient MM cells demonstrated
      similar results, without significant cytotoxicity against normal lymphocytes and
      bone marrow stromal cells (BMSCs). Importantly, LBW242 abrogates paracrine MM
      cell growth triggered by their adherence to BMSCs and overcomes MM cell growth
      and drug-resistance conferred by interleukin-6 or insulinlike growth factor-1.
      Overexpression of Bcl-2 similarly does not affect LBW242-induced cytotoxicity.
      Mechanistic studies show that LBW242-induced apoptosis in MM cells is associated
      with activation of caspase-8, caspase-9, and caspase-3, followed by PARP
      cleavage. In human MM xenograft mouse models, LBW242 is well tolerated, inhibits
      tumor growth, and prolongs survival. Importantly, combining LBW242 with novel
      agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      or the proteasome inhibitors bortezomib and NPI-0052, as well as with the
      conventional anti-MM agent melphalan, induces additive/synergistic anti-MM
      activity. Our study therefore provides the rationale for clinical protocols
      evaluating LBW242, alone and together with other anti-MM agents, to improve
      patient outcome in MM.

PMID- 17032926
TI  - The impact of altered p53 dosage on hematopoietic stem cell dynamics during
      aging.
AB  - A temporal decline in tissue stem cell functionality may be a key component of
      mammalian aging. The tumor suppressor p53 has recently been implicated as a
      potential regulator of aging. We examined age-associated hematopoietic stem cell
      (HSC) dynamics in mice with varying p53 activities. Reduced p53 activity in p53+/
      mice was associated with higher numbers of proliferating hematopoietic stem and
      progenitor cells in old age compared with aged wild-type (p53+/+) mice. We also
      assessed HSC dynamics in a p53 mutant mouse model (p53+/m) with higher apparent
      p53 activity than wild-type mice. The p53 hypermorphic (p53+/m) mice display
      phenotypes of premature aging. Many aged p53+/m organs exhibit reduced
      cellularity and atrophy, suggesting defects in stem-cell regenerative capacity.
      HSC numbers from old p53+/m mice fail to increase with age, unlike those of their
      p53+/+ and p53+/- counterparts. Moreover, transplantation of 500 HSCs from old
      p53+/m mice into lethally irradiated recipients resulted in reduced engraftment
      compared with old wild-type p53+/+ and p53+/- HSCs. Thus, alteration of p53
      activity affects stem-cell numbers, proliferation potential, and hematopoiesis in
      older organisms, supporting a model in which aging is caused in part by a decline
      in tissue stem cell regenerative function.

PMID- 17032927
TI  - CpG DNA activation and plasma-cell differentiation of CD27- naive human B cells.
AB  - Unmethylated CpG DNA activation of naive CD27- B cells has been reported to
      require B-cell-receptor (BCR) cross-linking. We describe a culture system using
      CpG DNA with sequential steps for T-cell-independent activation of naive
      CD19+CD27- human peripheral blood B cells that induces efficient CD138+ plasma
      cell differentiation. CD27+ and CD27- B cells were cultured in a 3-step system:
      (1) days 0 to 4: CpG, IL-2/10/15; (2) days 4 to 7: IL-2/6/10/15 and anti-CD40L;
      (3) days 7 to 10: IL-6/15, IFN-alpha, hepatocyte growth factor, and hyaluronic
      acid. Both CD27+ and CD27- B cells up-regulated intracytoplasmic TLR-9 following
      CpG DNA activation. CD27- B-cell activation required cell-cell contact. Both
      naive and memory B cells progressed to a plasma-cell phenotype:
      CD19lowCD20lowCD27+CD38+HLA-DRlow. Seventy percent of the CD27--derived CD138+
      cells demonstrated productive V chain rearrangements without somatic mutations,
      confirming their origin from naive precursors. Plasma cells derived from CD27+ B
      cells were primarily IgG+, while those from CD27- B cells were IgM+. Our results
      indicate that under certain conditions, naive B cells increase TLR-9 expression
      and proliferate to CpG DNA stimulation without BCR signaling. In addition to its
      immunologic significance, this system should be a valuable method to interrogate
      the antigenic specificity of naive B cells.

PMID- 17032928
TI  - Testosterone production in mice lacking inducible nitric oxide synthase
      expression is sensitive to restraint stress.
AB  - Immobilization stress (IMO) induces a rapid increase in glucocorticoid secretion
      [in rodents, corticosterone CORT)] and this is associated with decreased
      circulating testosterone (T) levels. Nitric oxide (NO), a reactive free radical
      and neurotransmitter, has been reported to be produced at higher rates in tissues
      such as brain during stress. The biosynthesis of T is also known to be
      dramatically suppressed by NO. Specifically, the inducible isoform of nitric
      oxide synthase (iNOS) was directly implicated in this suppression. To assess the
      respective roles of CORT and NO in stress-mediated inhibition of T production,
      adult wild-type (WT) and inducible nitric oxide synthase knockout (iNOS(-/-))
      male mice were evaluated. Animals of each genotype were assigned to either basal
      control or 3-h IMO groups. Basal plasma and testicular T levels were equivalent
      in both genotypes, whereas testicular weights of mutant mice were significantly
      higher compared with WT animals. Exposure to 3-h IMO increased plasma CORT and
      decreased T concentrations in mice of both genotypes. Testicular T levels were
      also affected by stress in WT and mutant males, being sharply reduced in both
      genotypes. However, the concentrations of nitrite and nitrate, the stable
      metabolites of NO measured in testicular extracts, did not differ between control
      and stressed WT and iNOS(-/-) mice. These results support the hypothesis that
      CORT, but not NO, is a plausible candidate to mediate rapid stress-induced
      suppression of Leydig cell steroidogenesis.

PMID- 17032929
TI  - Effects of transient PTH on early proliferation, apoptosis, and subsequent
      differentiation of osteoblast in primary osteoblast cultures.
AB  - In primary calvarial osteoblast cultures derived from transgenic mice expressing
      green fluorescent protein (GFP) under the control of 3.6-kb Col1a1 promoter, the
      emergence of GFP signal marks the transition of multipotential osteoprogenitors
      into preosteoblasts. Early transient treatment (days 1-7) of these cultures with
      parathyroid hormone (PTH) has an anabolic effect that is not associated with an
      increase in total DNA content or cell number in day 21 cultures. In the present
      study, the effect of early PTH treatment on cell proliferation and apoptosis was
      examined in greater detail in GFP(+) and GFP(-) cells using flow cytometry. In
      preconfluent cultures, PTH significantly reduced the proportion of cells in S
      phase but increased those in G(0)/G(1) and G(2)+M phases in both GFP(+) and GFP(
      ) subpopulations. PTH decreased apoptosis only in GFP(-) but not GFP(+) cells,
      indicating an increased survival of GFP(-) cells. In contrast, PTH did not change
      the amounts of cell proliferation and apoptosis seen in either compartment after
      these cultures reached confluence. To further assess the effect of early PTH
      treatment on osteogenic differentiation, secondary cultures of sorted GFP(+) or
      GFP(-) cells were obtained from day 7 primary cultures that had been treated for
      1 wk with PTH. This treatment resulted in larger areas of GFP expression
      accompanied by increased xylenol orange/von Kossa staining in the secondary
      cultures of GFP fractions. Early transient PTH treatment appears to enhance the
      commitment of progenitor cells to an osteogenic fate and results in a higher
      proportion of cells that achieve full osteoblast differentiation.

PMID- 17032930
TI  - Risk of venous thromboembolism among hospitalized medically ill patients.
AB  - PURPOSE: The 90-day risk of venous thromboembolism (VTE) among medically ill
      patients admitted to a hospital was estimated and is discussed. SUMMARY: Patients
      aged > or =40 years who were hospitalized between January 1, 1998, and June 30,
      2002, for reasons other than traumatic injury, labor and delivery, mental
      disorder, or VTE and who did not undergo surgery were identified in a large U.S.
      healthcare claims database. Patients receiving anticoagulants in the 90-day
      period preceding hospital admission were excluded. We estimated the percentage of
      study subjects who developed clinical deep-vein thrombosis (DVT) or pulmonary
      embolism (PE) within 90 days of hospital admission using Kaplan-Meier methods. We
      also estimated hazard ratios (HRs) for potential risk factors for VTE using
      univariate and stepwise multivariate Cox proportional hazards regression models.
      Among 92,162 study subjects, 1468 (1.59%) developed clinical DVT or PE within 90
      days of hospital admission; 18% of these events occurred postdischarge. In
      multivariate analyses, significant risk factors for clinical VTE included: 1)
      history of cancer (HR, 1.67; 95% confidence interval [CI], 1.45-1.93); 2) history
      of VTE within six months of index admission (HR, 6.14; 95% CI, 4.74-7.96); 3)
      operating room procedure within 30 days of index admission (HR, 1.81; 95% CI,
      1.47-2.24); 4) peripheral artery disease during index admission (HR, 1.68; 95%
      CI, 1.28-2.21); and 5) heart failure during index admission (HR, 1.72; 95% CI,
      1.52-1.95). CONCLUSION: The risk of clinical VTE among medically ill patients
      admitted to a hospital, although less than that of patients undergoing major
      surgery, is not negligible. Patients with a history of recent VTE or surgery,
      those who are admitted to the intensive care unit, those with an admitting
      diagnosis of heart failure, and those with active cancer are at especially high
      risk of VTE and deserve increased consideration for prophylaxis.

PMID- 17032931
TI  - Thromboprophylaxis in medically ill patients at risk for venous thromboembolism.
AB  - PURPOSE: According to guidelines from the American College of Chest Physicians,
      low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) should be
      prescribed to medical (nonsurgical) patients at high risk of venous
      thromboembolism. Thromboprophylaxis and mortality rates were determined in
      medical inpatients with indications for thromboprophylaxis. Cost differences
      between patient groups were investigated and are discussed. SUMMARY: Using
      Solucient's ACTracker Inpatient Database, medical discharges between January 2001
      and December 2004 were extracted and patients who had indications for
      thromboprophylaxis (acute myocardial infarction, ischemic stroke, cancer, heart
      failure, or severe lung disease) were identified. Patients < 40 years or with
      deep-vein thrombosis or pulmonary embolism, active peptic ulcer, malignant
      hypertension, blood disease, HIV infection, or intubation of gastrointestinal or
      respiratory tract were excluded. Rates of thromboprophylaxis and mortality were
      compared between groups. Mean total drug costs and hospital costs per patient
      discharge were compared between patient groups. Of 12,887,080 medical discharges
      extracted from 330 hospitals, there were 2,367,362 patients with indications for
      thromboprophylaxis. Patients were subdivided on the basis of whether they
      received thromboprophylaxis (n = 717,850) or not (n = 1,649,512). The
      thromboprophylaxis rate was low, despite increasing from 26% to 33% over the
      study period. Patients receiving thromboprophylaxis had significantly lower risk
      adjusted mortality rates than those who did not (p < 0.001), except those with
      ischemic stroke. The mean total drug cost per patient receiving LMWH and UFH
      ($791 and $569, respectively) was higher than for patients not receiving
      thromboprophylaxis ($372) (p < 0.001). The mean total hospital cost per patient
      receiving UFH ($7615) was higher than for LMWH ($6866, p < 0.001). CONCLUSION:
      The thromboprophylaxis rate among medical patients was low, with no significant
      improvement between 2001 and 2004. Thromboprophylaxis can impact patient
      mortality rates. Economic evaluation revealed that the use of LMWH for
      thromboprophylaxis in at-risk medical patients was associated with higher total
      drug costs but lower total hospital costs than UFH. Efforts should be made to
      increase clinicians' awareness of clinical guidelines.

PMID- 17032932
TI  - Prevention of venous thromboembolism: clinical and economic implications.
      Introduction.

PMID- 17032933
TI  - Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic
      syndrome.
AB  - PURPOSE: Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are associated
      with major morbidity and mortality, with their burden often extending to longer
      term complications such as event recurrence and post-thrombotic syndrome (PTS).
      Few data exist on the overall economic burden of DVT and PE and their sequelae. A
      retrospective observational cohort study was conducted to determine the direct
      medical costs of a DVT or PE patient across the entire continuum of care.
      SUMMARY: Administrative claims data for patients with a DVT or PE diagnosis (ICD
      9-CM code) and patients with possible evidence of PTS between January 1, 1997,
      and March 31, 2004, were extracted from the PharMetrics Patient-Centric Database,
      which comprises fully adjudicated medical and pharmaceutical claims for U.S.
      health care-plan enrollees. Resource utilization and annualized direct medical
      costs of care for patients with DVT and/or PE were calculated and compared with
      matched controls. A total of 26,958 patients met the study inclusion criteria. Of
      the 17,634 patients evaluable for the PTS cohort, 663 (3.8%) patients experienced
      PTS. Patients with DVT, PE, or DVT and PE had higher annualized direct medical
      costs before the index (initial) DVT and/or PE event (median: $7227, $6381, and
      $6771, respectively) than controls (median: $1045). During and after the DVT/PE
      event, annualized median costs rose to $17,512, $18,901, and $25,554,
      respectively, compared with $680 in the control group. Annualized median total
      costs for the PTS group were $20,569 compared with $15,843 in matched controls
      with DVT and/or PE and no PTS. CONCLUSION: These data suggest that the initial
      acute DVT or PE event is associated with high total health care costs and that
      these costs are further increased by subsequent events such as recurrent DVT or
      PE and PTS. Early detection and appropriate treatment of this high-risk
      population have the potential for both clinical and economic benefits.

PMID- 17032934
TI  - A model of nitric oxide tubulovascular cross talk in a renal outer medullary
      cross section.
AB  - We developed a two-dimensional model of NO transport in a cross section of the
      inner stripe (IS) of the rat outer medulla to determine whether tubular and
      vascular generation of NO result in significant NO concentration (C(NO))
      differences between the periphery and the center of vascular bundles and thereby
      affect medullary blood flow distribution. Following the approach of Layton and
      Layton (Layton AT, Layton HE. Am J Physiol Renal Physiol 289: F1346-F1366, 2006),
      the structural heterogeneity of the IS was incorporated in a representative unit
      consisting of four concentric regions centered on a vascular bundle. Our model
      suggests that the diffusion distance of NO in the interstitium is limited to a
      few micrometers. We predict that, under basal conditions, epithelial NO
      generation raises the average C(NO) in pericytes surrounding peripheral
      descending vasa recta (DVR) by a few nanomoles relative to that in pericytes
      surrounding central DVR. The short descending limbs and long ascending limbs are
      found to exert the greatest effect on C(NO) in pericytes; long descending limbs
      and short ascending limbs only have a moderate effect, whereas outer medullary
      collecting ducts, which are situated far from the vascular bundle center, do not
      affect pericyte C(NO). Our results suggest that selective stimulation of
      epithelial NO production should significantly raise the periphery-to-center DVR
      diameter ratio, thereby increasing the outer medulla-to-inner medulla blood flow
      ratio. However, concomitant increases in epithelial superoxide (O(2)(-))
      production would counteract this effect. This model confirms the importance of NO
      and O(2)(-) interactions in mediating tubulovascular cross talk.

PMID- 17032935
TI  - New insights into the regulation of V-ATPase-dependent proton secretion.
AB  - The vacuolar H(+)-ATPase (V-ATPase) is a key player in several aspects of
      cellular function, including acidification of intracellular organelles and
      regulation of extracellular pH. In specialized cells of the kidney, male
      reproductive tract and osteoclasts, proton secretion via the V-ATPase represents
      a major process for the regulation of systemic acid/base status, sperm maturation
      and bone resorption, respectively. These processes are regulated via modulation
      of the plasma membrane expression and activity of the V-ATPase. The present
      review describes selected aspects of V-ATPase regulation, including recycling of
      V-ATPase-containing vesicles to and from the plasma membrane,
      assembly/disassembly of the two domains (V(0) and V(1)) of the holoenzyme, and
      the coupling ratio between ATP hydrolysis and proton pumping. Modulation of the V
      ATPase-rich cell phenotype and the pathophysiology of the V-ATPase in humans and
      experimental animals are also discussed.

PMID- 17032936
TI  - Endotoxin and cisplatin synergistically stimulate TNF-alpha production by renal
      epithelial cells.
AB  - Acute renal failure often occurs in the clinical setting of multiple renal
      insults. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the
      pathogenesis of cisplatin nephrotoxicity, ischemia-reperfusion injury, and
      endotoxin-induced acute renal failure. The current studies examined the
      interactions between cisplatin and endotoxin with particular emphasis on TNF
      alpha production. Treatment of cultured murine proximal tubule cells (TKPTS
      cells) with cisplatin resulted in a modest production of TNF-alpha, while
      treatment with endotoxin did not result in any TNF-alpha production. However, the
      combination of cisplatin and endotoxin resulted in large amounts of TNF-alpha
      synthesis and secretion. The stimulation of TNF-alpha production was dependent on
      cisplatin-induced activation of p38 MAPK and was associated with phosphorylation
      of the translation initiation factor eIF4E and its upstream kinase Mnk1.
      Inhibition of p38 MAPK and, to a lesser extent, ERK, reduced cisplatin+endotoxin
      stimulated TNF-alpha production and phosphorylation of Mnk1 and eIF4E. Synergy
      between cisplatin and endotoxin was also observed in certain tumor cell lines,
      but not in macrophages. In macrophages, in contrast to TKPTS cells, endotoxin
      alone activated p38 MAPK and stimulated TNF-alpha production with no added impact
      by cisplatin. The combination of cisplatin and endotoxin did not result in
      synergistic production of other cytokines, e.g., MCP-1 and MIP2, by TKPTS cells.
      In summary, these studies indicate that cisplatin sensitizes renal epithelial
      cells to endotoxin and dramatically increases the translation of TNF-alpha mRNA
      in a p38 MAPK-dependent manner. These interactions between cisplatin and
      endotoxin may be relevant to the pathogenesis of cisplatin nephrotoxicity in
      humans.

PMID- 17032937
TI  - Statin-sensitive endocytosis of albumin by glomerular podocytes.
AB  - Glomerular podocytes are critical regulators of glomerular permeability via the
      slit diaphragm and may play a role in cleaning the glomerular filter. Whether
      podocytes are able to endocytose proteins is uncertain. We studied protein
      endocytosis in conditionally immortalized mouse and human podocytes using FITC
      albumin by direct quantitative assay and by fluorescence microscopy and electron
      microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human,
      rat, and mouse podocytes. Both mouse and human podocytes displayed specific one
      site binding for FITC-albumin with K(d) of 0.91 or 0.44 mg/ml and B(max) of 3.15
      or 0.81 microg/mg cell protein, respectively. In addition, they showed avid
      endocytosis of FITC-albumin with K(m) of 9.48 or 4.5 mg/ml and V(max) of 474.3 or
      97.4 microg.mg cell protein(-1).h(-1), respectively. Immunoglobulin and
      transferrin were inefficient competitors of this process, indicating some
      specificity for albumin. Accumulation of endocytosed albumin could be
      demonstrated in intracellular vesicles by fluorescence confocal microscopy and
      electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin.
      In vivo accumulation of albumin was found in all three species but was most
      pronounced in the rat. We conclude that podocytes are able to endocytose protein
      in a statin-sensitive manner. This function is likely to be highly significant in
      health and disease. In addition, protein endocytosis by podocytes may represent a
      useful, measurable phenotypic characteristic against which potentially injurious
      or beneficial interventions can be assessed.

PMID- 17032938
TI  - Regulation of renal glucose transporters during severe inflammation.
AB  - Severe sepsis is accompanied by acute renal failure (ARF) with renal tubular
      dysfunction and glucosuria. In this study, we aimed to determine the regulation
      of renal tubular glucose transporters during severe experimental inflammation.
      Male C57BL/6J mice were injected with LPS or proinflammatory cytokines, and renal
      perfusion, glomerular filtration rate (GFR), fractional glucose excretion, and
      expression of tubular glucose transporters were determined. We found a decreased
      plasma glucose concentration with impaired renal tissue perfusion and GFR and
      increased fractional glucose excretion associated with decreased expression of
      SGLT2, SGLT3, and GLUT2 after LPS injection. Similar alterations were observed
      after application of TNF-alpha, IL-1beta, IL-6, or IFN-gamma. To clarify the role
      of proinflammatory cytokines, we performed LPS injections in knockout mice with
      deficiencies for TNF-alpha, IL-1 receptor type 1, IFN-gamma, or IL-6 as well as
      LPS injections in glucocorticoid-treated wild-type mice. LPS-induced alterations
      of glucose transporters also were present in single-cytokine knockout mice. In
      contrast, glucocorticoid treatment clearly attenuated LPS-induced changes in
      renal glucose transporter expression and improved GFR and fractional glucose
      excretion. LPS-induced decrease of renal perfusion was not improved by
      glucocorticoids, indicating a minor role of ischemia in the development of septic
      renal dysfunction. Our results demonstrate modifications of tubular glucose
      transporters during severe inflammation that are probably mediated by
      proinflammatory cytokines and account for the development of ARF with increased
      fractional glucose excretion. In addition, our findings provide an explanation
      why single anti-cytokine strategies fail in the therapy of septic patients and
      contribute to an understanding of the beneficial effects of glucocorticoids on
      septic renal dysfunction.

PMID- 17032939
TI  - Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat.
AB  - TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with
      subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal
      tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular
      filtered albumin each day. Excess filtered albumin may contribute to PTC damage
      and tubulointerstitial disease. This investigation examined the role of ANG II
      induced oxidative stress in PTC structural remodeling: whether such changes could
      be modified with in vivo treatment with ANG type 1 receptor (AT(1)R) blockade
      (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age
      matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1
      mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-beta
      D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and
      x60,000 transmission electron microscopy images were used to assess PTC
      microvilli structure. There were significant differences in systolic blood
      pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and
      PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean
      diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated
      strongly with albuminuria (r(2) = 0.83) and moderately with MDA (r(2) = 0.49),
      and there was an increase in the ratio of abnormal forms of microvilli in placebo
      treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT(1)R
      blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-beta-d
      glucosaminidase; both therapies corrected abnormalities in oxidative stress and
      PTC microvilli remodeling. These data indicate that PTC structural damage in the
      Ren2 rat is related to the oxidative stress response to ANG II and/or
      albuminuria.

PMID- 17032940
TI  - Candesartan prevents long-term impairment of renal function in response to
      neonatal partial unilateral ureteral obstruction.
AB  - Angiotensin II (ANG II) plays an important role in the development of obstructive
      nephropathy. Here, we examined the effects of the ANG II receptor type 1 (AT1R)
      blockade using candesartan on long-term renal molecular and functional changes in
      response to partial unilateral ureteral obstruction (PUUO). Newborn rats were
      subjected to severe PUUO or sham operation (Sham) within the first 48 h of life.
      Candesartan was provided in the drinking water (10 mg.kg(-1).day(-1)) from day 21
      of life until 10 wk of age. Renal blood flow (RBF) was evaluated by MRI,
      glomerular filtration rate (GFR) was measured using the renal clearance of (51)Cr
      EDTA, and the renal expression of Na-K-ATPase and the collecting duct water
      channel aquaporin-2 (AQP2) was examined by immunoblotting and
      immunocytochemistry. At 10 wk of age, PUUO significantly reduced RBF (0.8 +/- 0.1
      vs. 1.6 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and GFR (37 +/- 16 vs.
      448 +/- 111 microl.min(-1).100 g body wt(-1); P < 0.05) compared with Sham.
      Candesartan prevented the RBF reduction (PUUO+CAN: 1.6 +/- 0.2 vs. PUUO: 0.8 +/-
      0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and attenuated the GFR reduction
      (PUUO+CAN: 265 +/- 68 vs. PUUO: 37 +/- 16 microl.min(-1).100 g body wt(-1); P <
      0.05). PUUO was also associated with a significant downregulation in the
      expression of Na-K-ATPase (75 +/- 12 vs. 100 +/- 5%, P < 0.05) and AQP2 (52 +/-
      15 vs. 100 +/- 4%, P < 0.05), which were also prevented by candesartan (Na-K
      ATPase: 103 +/- 8 vs. 100 +/- 5% and AQP2: 74 +/- 13 vs. 100 +/- 4%). These
      findings were confirmed by immunocytochemistry. Consistent with this, candesartan
      treatment partly prevented the reduction in solute free water reabsorption and
      attenuated fractional sodium excretion in rats with PUUO. In conclusion,
      candesartan prevents or attenuates the reduction in RBF, GFR and dysregulation of
      AQP2 and Na-K-ATPase in response to congenital PUUO in rats, suggesting that AT1R
      blockade may protect the neonatally obstructed kidney against development of
      obstructive nephropathy.

PMID- 17032941
TI  - Stanniocalcin-1 regulates endothelial gene expression and modulates
      transendothelial migration of leukocytes.
AB  - The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1
      (STC1) inhibits monocyte chemotactic protein-1- and stromal-derived factor-1alpha
      (SDF-1alpha)-mediated chemotaxis and diminishes chemokinesis in macrophage-like
      RAW264.7 and U937 cells in a manner that may involve attenuation of the
      intracellular calcium signal. STC1 is strongly induced in the kidney following
      obstructive injury. We hypothesized that STC1 may serve to attenuate the influx
      of inflammatory cells to the site of tissue injury. In this study, we examined
      the effect of STC1 on the migration of freshly isolated human macrophages,
      neutrophils, and T and B lymphocytes through quiescent or IL-1beta-treated human
      umbilical vein endothelial cell (HUVEC) monolayers. STC1 inhibited transmigration
      of macrophages and T lymphocytes through quiescent or IL-1beta-activated HUVECs
      but did not attenuate the transmigration of neutrophils and B lymphocytes. STC1
      regulates gene expression in cultured endothelial cells and is detected on the
      apical surface of endothelial cells in vivo. The data suggest that STC1 plays a
      critical role in transendothelial migration of inflammatory cells and is involved
      in the regulation of numerous aspects of endothelial function.

PMID- 17032942
TI  - Intravenous bilirubin provides incomplete protection against renal ischemia
      reperfusion injury in vivo.
AB  - Exogenous bilirubin (BR) substitutes for the protective effects of heme oxygenase
      (HO) in several organ systems. Our objective was to investigate the effects of
      exogenous BR in an in vivo model of ischemia-reperfusion injury (IRI) in the rat
      kidney. Four groups of male Sprague-Dawley rats were anesthetized using
      isoflurane in oxygen and treated with 1) 5 mg/kg intravenous (iv) BR, 1 h before
      ischemia and 6-h reperfusion; 2) vehicle 1 h before ischemia and 6-h reperfusion;
      3) 20 mg/kg iv BR, 1 h before and during ischemia; and 4) vehicle 1 h before and
      during ischemia. Bilateral renal clamping (30 min) was followed by 6-h
      reperfusion. Infusion of 5 mg/kg iv BR achieved target levels in the serum at 6 h
      postischemia (31 +/- 9 micromol/l). Infusion of 20 mg/kg BR reached 50 +/- 22
      micromol/l at the end of ischemia, and a significant improvement was seen in
      serum creatinine at 6 h (1.07 +/- 28 vs. 1.38 +/- 0.18 mg/dl, P = 0.043).
      Glomerular filtration rate, estimated renal plasma flow, fractional excretion of
      electrolytes, and renal vascular resistance were not significantly improved in BR
      treated groups. Histological grading demonstrated a trend toward preservation of
      cortical proximal tubules in rats receiving 20 mg/kg iv BR compared with control;
      however, neither BR dose provided protection against injury to the renal medulla.
      At the doses administered, iv BR did not provide complete protection against IRI
      in vivo. Combined supplementation of both BR and carbon monoxide may be required
      to preserve renal blood flow and adequately substitute for the protective effects
      of HO in vivo.

PMID- 17032943
TI  - Proceedings of the Consensus Conference "The Science of Surge", May 17, 2006, San
      Francisco, California, USA.

PMID- 17032944
TI  - Current status of surge research.
AB  - The dramatic escalation of bioterrorism and public health emergencies in the
      United States in recent years unfortunately has coincided with an equally
      dramatic decline in the institutions and services we rely on for emergency
      preparedness. Hospitals in nearly every metropolitan area in the country have
      closed; those that remain open have reduced the number of available beds. "Just
      in time" supplies and health professional shortages have further compromised the
      nation's overall surge capacity. Emergency departments routinely operate at
      capacity. These circumstances make evidence-based research on emergency
      preparedness and surge capacity both more urgently needed and more complex. The
      Agency for Healthcare Research and Quality and other government and private
      agencies have been rapidly widening the field of knowledge in this area in recent
      months and years. This report focuses primarily on the work of the Agency for
      Healthcare Research and Quality.

PMID- 17032945
TI  - Metrics in the science of surge.
AB  - Metrics are the driver to positive change toward better patient care. However,
      the research into the metrics of the science of surge is incomplete, research
      funding is inadequate, and we lack a criterion standard metric for identifying
      and quantifying surge capacity. Therefore, a consensus working group was formed
      through a "viral invitation" process. With a combination of online discussion
      through a group e-mail list and in-person discussion at a breakout session of the
      Academic Emergency Medicine 2006 Consensus Conference, "The Science of Surge,"
      seven consensus statements were generated. These statements emphasize the
      importance of funded research in the area of surge capacity metrics; the utility
      of an emergency medicine research registry; the need to make the data available
      to clinicians, administrators, public health officials, and internal and external
      systems; the importance of real-time data, data standards, and electronic
      transmission; seamless integration of data capture into the care process; the
      value of having data available from a single point of access through which data
      mining, forecasting, and modeling can be performed; and the basic necessity of a
      criterion standard metric for quantifying surge capacity. Further consensus work
      is needed to select a criterion standard metric for quantifying surge capacity.
      These consensus statements cover the future research needs, the infrastructure
      needs, and the data that are needed for a state-of-the-art approach to surge and
      surge capacity.

PMID- 17032946
TI  - The measurement of daily surge and its relevance to disaster preparedness.
AB  - This article reviews what is known about daily emergency department (ED) surge
      and ED surge capacity and illustrates its potential relevance during a
      catastrophic event. Daily ED surge is a sudden increase in the demand for ED
      services. There is no well-accepted, objective measure of daily ED surge. The
      authors propose that daily and catastrophic ED surge can be measured by the
      magnitude of the surge, as well as by the nature and severity of the illnesses
      and injuries that patients present with during the surge. The magnitude of an ED
      surge can be measured by the patient arrival rate per hour. The nature and
      severity of the surge can be measured by the type (e.g., trauma vs. infection vs.
      biohazard) and acuity (e.g., triage level) of the surge. Surge capacity is
      defined as the extent to which a system can respond to a rapid and sizeable
      increase in the demand for resources. ED surge capacity includes multiple
      dimensions, such as systems, space, staffing, and supplies. A multidimensional
      measure is needed that reflects both the core components and their relative
      contribution to ED surge capacity. Although many types of factors may influence
      ED surge capacity, relatively little formal research has been conducted in this
      area. A better understanding of daily ED surge capacity and influencing factors
      will improve our ability to simulate the potential impact that different types of
      catastrophic events may have on the surge capacity of hospital EDs nationwide.

PMID- 17032947
TI  - Research priorities for surge capacity.
AB  - The 2006 Academic Emergency Medicine Consensus Conference discussed key concepts
      within the field of surge capacity. Within the breakout session on research
      priorities, experts in disaster medicine and other related fields used a
      structured nominal-group process to delineate five critical areas of research. Of
      the 14 potential areas of discovery identified by the group, the top five were
      the following: 1) defining criteria and methods for decision making regarding
      allocation of scarce resources, 2) determining effective triage protocols, 3)
      determining key decision makers for surge-capacity planning and means to evaluate
      response efficacy (e.g., incident command), 4) developing effective communication
      and information-sharing strategies (situational awareness) for public-health
      decision support, and 5) developing methods and evaluations for meeting workforce
      needs. Five working groups were formed to consider the above areas and to devise
      sample research questions that were refined further by the entire group of
      participants.

PMID- 17032948
TI  - Caveat usare: actuarial schemes in real life.

PMID- 17032949
TI  - Suicide risk assessment: is clinical experience enough?

PMID- 17032950
TI  - Diversion to the mental health system: emergency psychiatric evaluations.
AB  - In Maryland, any citizen may petition to have individuals brought against their
      will for an examination by a physician. In this retrospective chart review, we
      evaluated the characteristics of 300 persons referred to the Johns Hopkins
      Hospital on emergency petitions. Sixty-one percent of petitions described
      individuals who made verbal or physical threats of self-harm. Forty-seven percent
      of the petitions described individuals who could have been arrested based on
      dangerousness to others or property, but were instead diverted to the emergency
      room for psychiatric evaluation. Although not promoted as a jail diversion
      program, this process has the potential to direct mentally ill citizens
      appropriately from the criminal justice system into the mental health system.
      Greater involvement of mental health professionals at all stages, including
      police training and participation in crisis response teams in the community, may
      improve this process.

PMID- 17032951
TI  - Use of the criminal justice system to leverage mental health treatment: effects
      on treatment adherence and satisfaction.
AB  - In efforts to divert persons with mental illness from jails and prisons, the
      option of community mental health treatment in lieu of incarceration is sometimes
      offered. In addition, community treatment can be mandated, or "leveraged," as a
      condition of probation or parole. However, little is known about the
      characteristics and attitudes of persons who are and who are not leveraged into
      community mental health treatment via the criminal justice (CJ) system. In the
      present study, over 1,000 outpatients with mental disorders were queried about
      their experiences with CJ leverages, as well as their clinical and treatment
      histories. Persons who had experienced at least one form of CJ leverage were more
      likely to be younger and male and to have more hospitalizations than persons who
      had never experienced a CJ leverage. However, leverage experience was not
      associated with treatment compliance and satisfaction, or perceptions of coercion
      and mandate efficacy, particularly when demographic characteristics were
      considered.

PMID- 17032952
TI  - Commentary: coerced community mental health treatment--an added burden on an
      overstretched system.
AB  - The sudden and massive depopulation of psychiatric institutions that occurred in
      the 60s and 70s overwhelmed a fragmented and undersourced community mental health
      system, leading, in part, to the high number of chronically mentally ill
      individuals currently residing in jails and prisons, a situation that has been
      described as reinstitutionalization or transinstitutionalization. Any process
      that forces more people out of jails into mental health treatment in the
      community without a sound, effective, available, and accessible community mental
      health system of care is potentially catastrophic.

PMID- 17032953
TI  - Cultural stereotypes die hard: the case of transracial adoption.
AB  - Transracial adoption (commonly understood as the adoption of black children by
      white families) has been the subject of a persistent debate among adoption
      specialists, legal advocates, mental health professionals, and even civil rights
      advocates in this country for a long time. This has been so despite cumulative
      research evidence indicating that transracial adoptees can thrive and develop
      into confident adults with strong senses of identity and self-esteem. We contend
      that the evidence undergirding transracial adoption has not been effectively
      persuasive because of the tenacious and ubiquitous cultural belief that children
      and their potential adoptive parents should be matched along racial lines.
      However, the cultural principle of racial matching has also been diluted by
      judicial decisions that have narrowly allowed the use of race as one factor
      rather than as the controlling factor in adoption decisions. This article focuses
      on the use of a third element--federal statutory attempts intended to remove race
      as a controlling factor in child placement decisions. We will show how as a
      matter of public policy, the statutory efforts were meant to promote race-neutral
      approaches to adoption and to support transracial adoptions. However, in
      practice, the statutory attempts may still leave the door open to continued race
      matching, which suggests that the cultural preference for race-matching in the
      construction of families remains powerfully ingrained and difficult to eradicate.
      As a consequence, transracial adoption appears to maintain its status as a
      culturally suspect phenomenon.

PMID- 17032954
TI  - Commentary: cultural stereotypes can and do die: it's time to move on with
      transracial adoption.
AB  - This commentary argues that the Multiethnic Placement Act, designed to combat
      common cultural stereotypes, provides clear guidance to state child welfare
      agencies and the mental health professionals that serve them, eliminating any
      regular consideration of race in the foster and adoptive placement of children.
      Given recent enforcement action by the U.S. Department of Health and Human
      Services, those who ignore this guidance act at peril of subjecting state
      agencies to the significant financial penalties mandated for any violation of the
      law.

PMID- 17032955
TI  - Commentary: transracial adoption--changing trends and attitudes.
AB  - Legislating adoption practices is a stop-gap measure to protect the interests of
      potential adoptees and their would-be parents. As our society becomes better able
      to govern itself in these matters and reaches a consensus on humanitarian values,
      it is hoped that the need for legislation will diminish. In the meantime, we
      still have the best-interests test to guide us through new and sometimes troubled
      waters. We need to instill respect for all minority cultures while also
      incorporating them into the larger culture that one day will appreciate the
      values of tolerance and diversity.

PMID- 17032956
TI  - A study of geriatric forensic evaluees: who are the violent elderly?
AB  - The objective of this study was to examine a sample (n = 99) of elderly forensic
      evaluees to describe the psychiatric, medical, legal, and demographic
      characteristics of the sample and to examine which of these factors is associated
      with violent charges. Clinical data were gathered through retrospective chart
      review of patients aged 60 and over who were referred for criminal
      responsibility/competency-to-stand-trial evaluations from 1991 to 1998 at William
      S. Hall Psychiatric Institute in Columbia, South Carolina. Most (67.7%) of the
      sample was alcohol dependent, nearly one half (44.4%) had dementia, and close to
      one third (32.3%) had antisocial personality disorder. The majority of patients
      (60.6%) were facing violent charges and most (80.8%) were recidivists. In
      multivariate analysis, race, outpatient treatment status, crime location, and
      paranoia were all associated with violent charges. The implications and
      limitations of these data as applied to forensic treatment settings are
      discussed.

PMID- 17032958
TI  - Warning a potential victim of a person's dangerousness: clinician's duty or
      victim's right?
AB  - The legal duty of a psychiatrist or psychotherapist to warn an identifiable
      victim of a patient's serious threat of harm has been well recognized in U.S.
      jurisprudence and clinical practice since the Tarasoff decision of the Supreme
      Court of California in 1976. Warning practices vary over a spectrum ranging from
      those that are essentially legally required duties of clinicians to those based
      on rights of actual or potential victims to be warned of a specific event. These
      practices can be categorized as follows: (1) warning of the risk of violence; (2)
      warning of the threat of violence; (3) requested warning; and (4) criminal
      victims' warning mandated by statute. As legal requirements and clinical
      standards for Tarasoff-type warnings continue to evolve, it behooves mental
      health professionals to recognize these four different types of warnings.
      Although not all are equally supported in law, all four practices can appear to
      carry some measure of legal obligation.

PMID- 17032957
TI  - Commentary: older offenders--no place to go?
AB  - For offender groups, difficulties in definition of 'elderly' and 'older' are
      considerable. Adoption of chronological age cutoffs gives little indication of
      service need. Contrary to popular belief, there has been no upsurge of offending
      among people of 60 and over, but there has been an increase in their
      representation in the prison population. Older prisoners tend to have more mental
      and physical health care needs than younger prisoners and than their similarly
      aged peers in the community. Their needs may be more appropriately met in health
      care rather than criminal justice services. Neither health care nor criminal
      justice services, however, have yet made adequate specific provision for this
      group. Our commentary reviews current evidence for more appropriate and safer
      service responses.

PMID- 17032959
TI  - Long-term follow-up of exhibitionists: psychological, phallometric, and offense
      characteristics.
AB  - Exhibitionism has historically been viewed as more of a nuisance than a serious
      criminal justice matter. Research has demonstrated that the number of
      exhibitionists who are detected re-offending is a significant under
      representation of the number who actually re-offend. The objective of this study
      was to extend a previous study conducted on exhibitionists, while attempting to
      solve the limitations described in that study. Two hundred eight exhibitionists
      were assessed at a university teaching hospital between 1983 and 1996. Archival
      data were derived from police and medical files. Results indicated that, over a
      mean follow-up period of 13.24 years, 23.6, 31.3, and 38.9 percent of
      exhibitionists were charged with or convicted of sexual, violent, or criminal
      offenses, respectively. Undoubtedly, this is an under-representation of the true
      rate, as we have no way of knowing how many exhibitionists re-offended and did
      not get caught. Nevertheless, in the present investigation, sexual recidivists
      compared with non-recidivists were less educated, scored higher on the Michigan
      Alcohol Screening Test (MAST), the Psychopathy Checklist, Revised (PCL-R), and
      the Pedophile Index. Violent recidivists were also less educated and scored
      higher on the MAST, PCL-R, and the Pedophile Index, and had accumulated a greater
      number of prior violent or criminal charges and/or convictions. Criminal
      recidivists were less educated; scored higher on the MAST, Buss-Durkee Hostility
      Inventory (BDHI), PCL-R, and Pedophile Index; and had accumulated a greater
      number of prior sexual, violent, and criminal offenses. Finally, the hands-on
      sexual recidivists accumulated a greater number of prior violent and criminal
      charges and or convictions than did the hands-off sexual recidivists.

PMID- 17032960
TI  - The performance of incarcerated juveniles on the MacArthur Competence Assessment
      Tool-Criminal Adjudication (MacCAT-CA).
AB  - The MacArthur Competency Assessment Tool-Criminal Adjudication (MacCAT-CA) is a
      structured interview that assesses abilities related to an individual's
      competency to stand trial (CST). In the present study, we examined the
      performance of 247 juvenile offenders on the scales of the MacCAT-CA
      (Understanding, Reasoning, and Appreciation), along with several other variables
      (age, IQ, achievement level, experience with the juvenile justice system, and a
      screen for psychopathology) that may be related to CST. In general, results
      suggest that performance on the MacCAT-CA varied with age, with younger
      participants performing significantly worse than older juveniles. When compared
      with the normative data, the juveniles in the present sample demonstrated
      deficits in court-related skills measured by the MacCAT-CA across all age ranges.
      In addition, several other variables, including achievement level, intelligence
      level, and psychopathology, were differentially related to the three scales of
      the MacCAT-CA.

PMID- 17032961
TI  - Asperger's disorder and criminal behavior: forensic-psychiatric considerations.
AB  - Asperger's Disorder remains an under-diagnosed condition because of clinical
      unfamiliarity with its adult presentation. As forensic clinicians become familiar
      with the presentation of Asperger's disorder, it appears that affected
      individuals are over-represented in forensic criminal settings. Unique features
      of such persons may heighten their risks for engaging in criminal behavior. Both
      Theory of Mind deficits and a predilection for intense narrow interests, when
      coupled with deficient social awareness of salient interpersonal and social
      constraints on behavior, can result in criminal acts. We discuss comorbidities of
      forensic relevance. We present several cases that highlight these issues and
      review the relevant forensic literature. Furthermore, there may be valid
      questions as to degree of criminal responsibility in such persons. From a
      neuropsychiatric perspective, these disorders appear to have a biological
      underpinning for deficits in empathy, a finding that may have important
      repercussions when assessing remorse in criminal proceedings.

PMID- 17032963
TI  - Commentary: psychiatric advance directives at a crossroads--when can PADs be
      overridden?
AB  - Current statutes enabling psychiatric advance directives (PADs) typically include
      provisions allowing override of patients' choices by treatment staff. Lest the
      purpose of the PAD be vitiated by too broad an application of the override
      mechanism, its use should be carefully limited. In inpatient settings, voluntary
      patients should have the right to decline treatments in advance, although not an
      absolute right to demand treatments of their choosing. The situation of
      involuntary patients is more complex. Permitting PADs to trump commitment
      statutes would undercut the combined parens patriae/police power rationale for
      commitment, a path taken currently by no U.S. jurisdiction. Moreover, PADs should
      not be permitted to negate the usual mechanisms for involuntary treatment of
      committed patients; to do otherwise risks forcing facilities to confine
      indefinitely persons they cannot treat. Even in those circumstances, however,
      where PADs provide evidence of reasonable patient preferences (e.g., for one
      medication over another), the choices they embody should be respected.

PMID- 17032962
TI  - Superseding psychiatric advance directives: ethical and legal considerations.
AB  - Psychiatric advance directives (PADs) were introduced in the 1980s as legal
      instruments for psychiatric patients to retain some choice over their own mental
      health treatment during periods of decisional incapacity. However, PADs are
      nested in larger structures of mental health law and policy that protect the
      interests of parties other than the patient, and which, in situations of conflict
      involving the treatment of incapacitated patients, tend to favor the clinician's
      professional judgment over the patient's manifest wishes to avoid standard
      treatment. Thus, PADs are trumped by civil commitment law and may also be legally
      overridden by clinicians who, acting in good faith, consider PAD instructions to
      be inconsistent with accepted clinical standards of care. We discuss
      philosophical-ethical and legal issues surrounding overriding PADs and offer
      analysis of the possible future of legal cases in which the question of
      overriding PADs and fiscal concerns may collide.

PMID- 17032964
TI  - Commentary: toward resolving some dilemmas concerning psychiatric advance
      directives.
AB  - Dilemmas about when psychiatric advance directives (PADs) should be overridden
      are complicated by conflicting legal frameworks that may nonetheless operate
      concurrently-a legal scheme based on decision-making capacity (or competency) set
      against a legal scheme based on civil commitment, in which the latter may "trump"
      the former. A single statute in which the strengths of both schemes are "fused"
      may be possible. There is evidence that the promise of PADs in enhancing
      patients' control over their treatment can be achieved without legislation for
      PADs and where civil commitment is given legal precedence. An example is the
      "joint crisis plan" in which, through a negotiation facilitated by an independent
      third party, a joint agreement is reached between patient and service provider
      about what treatment should be given when, as a result of a relapse of mental
      illness, the patient loses the ability to make treatment decisions. This clinical
      instrument may significantly reduce later involuntary treatment.

PMID- 17032965
TI  - Commentary: the climate for physician adherence to psychiatric advance
      directives.
AB  - Factors that may be significant in rationalizing physician overrides of
      psychiatric advance directives (PADs) are not only features of individual
      clinical scenarios, but also are artifacts of the faltering mental health system
      being navigated by both provider and patient. This system, frequently viewed as
      hostile to consumer choice and increasingly focused on reacting to recurrent
      crises, is not predisposed to accepting proactive, person-centered measures such
      as PADs. In fact, PADs may hold great promise in improving clinical outcomes and
      even reducing system costs. But to realize the full potentials of PADs requires
      that providers understand their roles in challenging or perpetuating problems in
      the larger mental health system.

PMID- 17032966
TI  - Electroconvulsive therapy: administrative codes, legislation, and professional
      recommendations.
AB  - Government regulatory involvement in electroconvulsive therapy (ECT) is due to
      several factors, including patient advocate groups, prior abuse by psychiatrists,
      and a general trend of state authority to move into areas traditionally governed
      by medical authorities. Regardless of the specific reasons, ECT is both highly
      effective in the treatment of many psychiatric disorders and heavily regulated by
      state administrative codes and legislation. The purpose of this article is to
      conduct a systematic review of the state administrative codes and legislation for
      the 50 states, the District of Columbia, and Puerto Rico and to compare the
      findings with professional recommendations for the administration of ECT.

PMID- 17032974
TI  - The cover. An October Day.

PMID- 17032975
TI  - A piece of my mind. The imaginary safety net.

PMID- 17032976
TI  - Genetic link found for premature birth risk.

PMID- 17032977
TI  - High suicide risk found for patients with head and neck cancer.

PMID- 17032978
TI  - Insulin effects weigh heavy on the brain.

PMID- 17032979
TI  - Aging brings new challenges for polio survivors.

PMID- 17032980
TI  - Pharmacotherapy and behavioral intervention for alcohol dependence.

PMID- 17032981
TI  - Pharmacotherapy and behavioral intervention for alcohol dependence.

PMID- 17032982
TI  - Inside baseball.

PMID- 17032983
TI  - Inside baseball.

PMID- 17032984
TI  - Glucose fluctuations and oxidative stress.

PMID- 17032985
TI  - Translation of research evidence from animals to humans.

PMID- 17032986
TI  - Risk of myocardial infarction in patients with psoriasis.
AB  - CONTEXT: Psoriasis is the most common T-helper cell type 1 (T(H)1) immunological
      disease. Evidence has linked T(H)1 diseases to myocardial infarction (MI).
      Psoriasis has been associated with cardiovascular diseases, but has only been
      investigated in hospital-based studies that did not control for major
      cardiovascular risk factors. OBJECTIVE: To determine if within a population-based
      cohort psoriasis is an independent risk factor for MI when controlling for major
      cardiovascular risk factors. DESIGN, SETTING, AND PATIENTS: A prospective,
      population-based cohort study in the United Kingdom of patients with psoriasis
      aged 20 to 90 years, comparing outcomes among patients with and without a
      diagnosis of psoriasis. Data were collected by general practitioners as part of
      the patient's medical record and stored in the General Practice Research Database
      between 1987 and 2002, with a mean follow-up of 5.4 years. Adjustments were made
      for hypertension, diabetes, history of myocardial infarction, hyperlipidemia,
      age, sex, smoking, and body mass index. Patients with psoriasis were classified
      as severe if they ever received a systemic therapy. Up to 5 controls without
      psoriasis were randomly selected from the same practices and start dates as the
      patients with psoriasis. A total of 556,995 control patients and patients with
      mild (n = 127,139) and severe psoriasis (n = 3837) were identified. MAIN OUTCOME
      MEASURE: Incident MI. RESULTS: There were 11,194 MIs (2.0%) within the control
      population and 2319 (1.8%) and 112 (2.9%) MIs within the mild and severe
      psoriasis groups, respectively. The incidences per 1000 person-years for control
      patients and patients with mild and severe psoriasis were 3.58 (95% confidence
      interval [CI], 3.52-3.65), 4.04 (95% CI, 3.88-4.21), and 5.13 (95% CI, 4.22
      6.17), respectively. Patients with psoriasis had an increased adjusted relative
      risk (RR) for MI that varied by age. For example, for a 30-year-old patient with
      mild or severe psoriasis, the adjusted RR of having an MI is 1.29 (95% CI, 1.14
      1.46) and 3.10 (95% CI, 1.98-4.86), respectively. For a 60-year-old patient with
      mild or severe psoriasis, the adjusted RR of having an MI is 1.08 (95% CI, 1.03
      1.13) and 1.36 (95% CI, 1.13-1.64), respectively. CONCLUSIONS: Psoriasis may
      confer an independent risk of MI. The RR was greatest in young patients with
      severe psoriasis.

PMID- 17032987
TI  - Respiratory symptoms, pulmonary function, and markers of inflammation among bar
      workers before and after a legislative ban on smoking in public places.
AB  - CONTEXT: Scotland prohibited smoking in confined public places on March 26, 2006.
      OBJECTIVE: To investigate the association of smoke-free legislation with
      symptoms, pulmonary function, and markers of inflammation of bar workers. DESIGN,
      SETTING, AND PARTICIPANTS: This prospective observational study was conducted in
      Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and
      asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed
      the study per protocol. MAIN OUTCOME MEASURES: Respiratory and sensory symptoms,
      spirometry measurements, serum cotinine levels, peripheral inflammatory cell
      count, asthma quality-of-life scores, and exhaled nitric oxide levels were
      evaluated before and after introduction of the smoking ban. RESULTS: For the per
      protocol analysis, the percentage of bar workers with respiratory and sensory
      symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n =
      41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001)
      and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months
      afterward. Forced expiratory volume in the first second increased from 96.6%
      predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7%
      (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels
      decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to 
      1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34
      ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from
      7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260
      cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL;
      95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers
      also had less airway inflammation, with a reduction in exhaled nitric oxide from
      34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change;
      95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased
      from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049).
      CONCLUSIONS: Smoke-free legislation was associated with significant early
      improvements in symptoms, spirometry measurements, and systemic inflammation of
      bar workers. Asthmatic bar workers also had reduced airway inflammation and
      improved quality of life.

PMID- 17032988
TI  - Long-term outcome of primary percutaneous coronary intervention vs prehospital
      and in-hospital thrombolysis for patients with ST-elevation myocardial
      infarction.
AB  - CONTEXT: Whether the superior results of percutaneous coronary intervention (PCI)
      reported in clinical trials in which patients with ST-segment elevation
      myocardial infarction (STEMI) received reperfusion treatment can be replicated in
      daily practice has been questioned, especially whether it is superior to
      prehospital thrombolysis (PHT). OBJECTIVE: To evaluate the outcome of different
      reperfusion strategies in consecutive STEMI patients. DESIGN, SETTING, AND
      PATIENTS: A prospective observational cohort study of 26 205 consecutive STEMI
      patients in the Register of Information and Knowledge about Swedish Heart
      Intensive Care Admissions (RIKS-HIA) who received reperfusion therapy within 15
      hours of symptom onset. The registry includes more than 95% of all Swedish
      patients, of all ages, who were treated in a coronary intensive care unit between
      1999 and 2004. INTERVENTIONS: Seven thousand eighty-four patients underwent
      primary PCI; 3078, PHT; and 16 043, in-hospital thrombolysis (IHT). MAIN OUTCOME
      MEASURES: Mortality, reinfarction, and readmissions as reported in the National
      Health Registries through December 31, 2005. RESULTS: After adjusting for younger
      age and less comorbidity, primary PCI was associated with lower mortality than
      IHT at 30 days (344 [4.9%] vs 1834 [11.4%]; hazard ratio [HR], 0.61; 95%
      confidence interval [CI], 0.53-0.71) and at 1 year (541 [7.6%] vs 2555 [15.9%];
      HR, 0.68; 95% CI, 0.60-0.76). Also primary PCI correlated with lower mortality
      than PHT at 30 days (344 [4.9%] vs 234 [7.6%]; HR, 0.70; 95% CI, 0.58-0.85) and 1
      year (541 [7.6%] vs 317 [10.3%]; HR, 0.81; 95% CI, 0.69-0.94). Prehospital
      thrombolysis predicted a lower mortality than IHT at 30 days (HR, 0.87; 95% CI,
      0.76-1.01) and at 1 year (HR, 0.84; CI 0.74-0.95). Beyond 2 hours' treatment
      delay, the observed mortality reductions with PHT tended to decrease while the
      benefits with primary PCI seemed to remain regardless of time delay. Primary PCI
      was also associated with shorter hospital stay and less reinfarction than either
      PHT or IHT. CONCLUSIONS: In unselected patients with STEMI, primary PCI, which
      compared favorably with IHT and PHT, was associated with reduced duration of
      hospital stay, readmission, reinfarction, and mortality.

PMID- 17032989
TI  - Nonmedical exemptions to school immunization requirements: secular trends and
      association of state policies with pertussis incidence.
AB  - CONTEXT: School immunization requirements have played a major role in controlling
      vaccine-preventable diseases in the United States. Most states offer nonmedical
      exemptions to school requirements (religious or personal belief). Exemptors are
      at increased risk of acquiring and transmitting disease. The role of exemption
      policies may be especially important for pertussis, which is endemic in the
      United States. OBJECTIVE: To determine if (1) the rates of nonmedical exemptions
      differ and have been increasing in states that offer only religious vs personal
      belief exemptions; (2) the rates of nonmedical exemptions differ and have been
      increasing in states that have easy vs medium and easy vs difficult processes for
      obtaining exemptions; and (3) pertussis incidence is associated with policies of
      granting personal belief exemptions, ease of obtaining exemptions, and acceptance
      of parental signature as sufficient proof of compliance with school immunization
      requirements. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 1991 through 2004
      state-level rates of nonmedical exemptions at school entry and 1986 through 2004
      pertussis incidence data for individuals aged 18 years or younger. MAIN OUTCOME
      MEASURES: State-level exemption rates and pertussis incidence. RESULTS: From 2001
      through 2004, states that permitted personal belief exemptions had higher
      nonmedical exemption rates than states that offered only religious exemptions,
      and states that easily granted exemptions had higher nonmedical exemption rates
      in 2002 through 2003 compared with states with medium and difficult exemption
      processes. The mean exemption rate increased an average of 6% per year, from
      0.99% in 1991 to 2.54% in 2004, among states that offered personal belief
      exemptions. In states that easily granted exemptions, the rate increased 5% per
      year, from 1.26% in 1991 to 2.51% in 2004. No statistically significant change
      was seen in states that offered only religious exemptions or that had medium and
      difficult exemption processes. In multivariate analyses adjusting for
      demographics, easier granting of exemptions (incidence rate ratio = 1.53; 95%
      confidence interval, 1.10-2.14) and availability of personal belief exemptions
      (incidence rate ratio = 1.48; 95% confidence interval, 1.03-2.13) were associated
      with increased pertussis incidence. CONCLUSIONS: Permitting personal belief
      exemptions and easily granting exemptions are associated with higher and
      increasing nonmedical US exemption rates. State policies granting personal belief
      exemptions and states that easily grant exemptions are associated with increased
      pertussis incidence. States should examine their exemption policies to ensure
      control of pertussis and other vaccine-preventable diseases.

PMID- 17032990
TI  - Do opiates affect the clinical evaluation of patients with acute abdominal pain?
AB  - CONTEXT: Clinicians have traditionally withheld opiate analgesia from patients
      with acute abdominal pain until after evaluation by a surgeon, out of concern
      that analgesia may alter the physical findings and interfere with diagnosis.
      OBJECTIVE: To determine the impact of opiate analgesics on the rational clinical
      examination and operative decision for patients with acute abdominal pain. DATA
      SOURCES AND STUDY SELECTION: MEDLINE (through May 2006), EMBASE, and hand
      searches of article bibliographies to identify placebo-controlled randomized
      trials of opiate analgesia reporting changes in the history, physical examination
      findings, or diagnostic errors (those resulting in "management errors," defined
      as the performance of unnecessary surgery or failure to perform necessary surgery
      in a timely fashion). DATA EXTRACTION: Two authors independently reviewed each
      study, abstracted data, and classified study quality. A third reviewer
      independently resolved discrepancies. DATA SYNTHESIS: Studies both in adults (9
      trials) and in children (3 trials) showed trends toward increased risks of
      altered findings on the abdominal examination due to opiate administration, with
      risk ratios for changes in the examination of 1.51 (95% confidence interval [CI],
      0.85 to 2.69) and 2.11 (95% CI, 0.60 to 7.35), respectively. When the analysis
      was restricted to the 8 adult and pediatric trials that reported significantly
      greater analgesia for patients who received opiates compared with those who
      received placebo, the risk of physical examination changes became significant
      (risk ratio, 2.13; 95% CI, 1.14 to 3.98). These trials exhibited significant
      heterogeneity (I2 = 68.6%; P = .002), and only 2 trials distinguished clinically
      significant changes such as loss of peritoneal signs from all other changes;
      consequently, we analyzed risk of management errors as a marker for important
      changes in the physical examination. Opiate administration had no significant
      association with management errors (+0.3% absolute increase; 95% CI, -4.1% to
      +4.7%). The 3 pediatric trials showed a nonsignificant absolute decrease in
      management errors (-0.8%; 95% CI, -8.6% to +6.9%). Across adult and pediatric
      trials with adequate analgesia, opiate administration was associated with a
      nonsignificant absolute decrease in the risk of management errors (-0.2%; 95% CI,
      -4.0% to +3.6%). CONCLUSIONS: Opiate administration may alter the physical
      examination findings, but these changes result in no significant increase in
      management errors. The existing literature does not rule out a small increase in
      errors, but this error rate reflects a conservative definition in which surgeries
      labeled as either delayed or unnecessary may have met appropriate standards of
      care. In published research reports, no patient experienced major morbidity or
      mortality attributable to opiate administration.

PMID- 17032991
TI  - Plan B and the politics of doubt.

PMID- 17032992
TI  - Banning smoking in public places: time to clear the air.

PMID- 17032994
TI  - JAMA patient page. Acute abdominal pain.

PMID- 17032995
TI  - Letter to the editor: The suckling-micturition reflex in cows.

PMID- 17032996
TI  - Modeling high-intensity pulsed electric field inactivation of a lipase from
      Pseudomonas fluorescens.
AB  - The inactivation kinetics of a lipase from Pseudomonas fluorescens (EC 3.1.1.3.)
      were studied in a simulated skim milk ultrafiltrate treated with high-intensity
      pulsed electric fields. Samples were subjected to electric field intensities
      ranging from 16.4 to 27.4 kV/cm for up to 314.5 micros, thus achieving a maximum
      inactivation of 62.1%. The suitability of describing experimental data using
      mechanistic first-order kinetics and an empirical model based on the Weibull
      distribution function is discussed. In addition, different mathematical
      expressions relating the residual activity values to field strength and treatment
      time are supplied. A first-order fractional conversion model predicted residual
      activity with good accuracy (A(f) = 1.018). A mechanistic insight of the model
      kinetics was that experimental values were the consequence of different
      structural organizations of the enzyme, with uneven resistance to the pulsed
      electric field treatments. The Weibull model was also useful in predicting the
      energy density necessary to achieve lipase inactivation.

PMID- 17032997
TI  - Ionic calcium determination in skim milk with molecular probes and front-face
      fluorescence spectroscopy: simple linear regression.
AB  - The purpose of this study was to determine if the ionic calcium content of skim
      milk could be determined using molecular probes and front-face fluorescence
      spectroscopy. Current methods for determining ionic calcium are not sensitive,
      overestimate ionic calcium, or require complex procedures. Molecular probes
      designed specifically for measuring ionic calcium could potentially be used to
      determine the ionic calcium content of skim milk. The goal of the current study
      was to develop foundation methods for future studies to determine ionic calcium
      directly in skim milk and other dairy products with molecular probes and
      fluorescence spectroscopy. In this study, the effect of pH on calcium-sensitive
      fluorescent probe (Rhod-5N and Fluo-5N) performance using various concentrations
      of skim milk was determined. The pH of diluted skim milk (1.9 to 8.9% skim milk),
      was adjusted to either 6.2 or 7.0, after which the samples were analyzed with
      fluorescent probes (1 microM) and front-face fluorescence spectroscopy. The ionic
      calcium content of each sample was also determined using a calcium ion-selective
      electrode. The results demonstrated that the ionic calcium content of each sample
      was highly correlated (R2 > 0.989) with the fluorescence intensities of the probe
      calcium adduct using simple linear regression. Higher than suggested ionic
      calcium contents of 1,207 and 1,973 microM were determined with the probes (Fluo
      5N and Rhod-5N) in diluted skim milk with pH 7.0 and 6.2, respectively. The
      fluorescence intensity of the probe-calcium adduct decreased with a decrease in
      pH for the same ionic calcium concentration. This study demonstrates that Fluo-5N
      and Rhod-5N can be used to determine the ionic-calcium content of diluted milk
      with front-face fluorescence spectroscopy. Furthermore, these probes may also
      have the potential to determine the ionic calcium content of undiluted skim milk.

PMID- 17032998
TI  - Improving the yield of Mozzarella cheese by phospholipase treatment of milk.
AB  - Part-skim Mozzarella cheese was manufactured from milk hydrolyzed with fungal
      phospholipase A1 prior to renneting. The phospholipase treatment reduced fat
      losses in whey and cooking water and increased cheese yield as a result of
      improved fat and moisture retention in the cheese curd. The amount of
      phospholipids in the whey was reduced because of improved retention of
      lysophospholipids in the cheese curd. Water binding in the fresh curds and young
      cheeses up to 3 wk of storage was investigated by a 1H nuclear magnetic resonance
      spin-spin relaxation technique. In the fresh curds, 2 dominant water fractions
      were present, characterized by average spin-spin relaxation times (T2) of 14 and
      86 to 89 ms, respectively. These 2 fractions of low- and high-molecular-mobility
      water were similar in all cheeses and presumed to represent water associated with
      the casein matrix and water present in the pores. A few hours after manufacture,
      cheeses made with phospholipase showed decreased T2 of the high-mobility
      fraction, indicating improved water-holding capacity. It is suggested that
      lysophospholipids released from the fat globule membranes act as surface-active
      agents in the cheese curd, helping emulsification of water and fat during
      processing and reducing syneresis. During 3 wk of storage after manufacture, the
      mobility of both water fractions increased in all cheeses, but was highest in the
      cheeses made with phospholipase. The increase in mobility during the first weeks
      of storage has earlier been ascribed to structural changes in the protein matrix,
      which in principle could be accelerated because of the higher moisture content.
      However, the microstructure of phospholipase-treated cheese was investigated by
      confocal laser scanning microscopy and found to be very similar to the control
      cheese during processing and up to 28 d of storage. In addition, flowability,
      stretchability, and browning were acceptable and similar in all the manufactured
      cheeses. Thus, phospholipase hydrolysis of cheese milk improved the cheese yield
      without changing the cheese microstructure, and resulted in cheese with
      functional properties that were identical to traditional Mozzarella cheese.

PMID- 17032999
TI  - Comparison of the compositional, microbiological, biochemical, and volatile
      profile characteristics of nine Italian ewes' milk cheeses.
AB  - Nine Italian ewes' milk cheeses were compared for compositional, microbiological,
      biochemical, and volatile profile characteristics. Mean values for the gross
      composition were rather similar among cheeses. The lowest pH values were found
      for cheeses that used primary starters. At the end of ripening, cheeses made from
      raw milk contained >6.0 log10 cfu/g of nonstarter lactic acid bacteria. Several
      species of lactobacilli were identified, but Lactobacillus plantarum and
      Lactobacillus paracasei were dominant. Random amplified polymorphic DNA-PCR
      analysis showed the biodiversity among the strains, and in several cases a
      relationship with the cheese of provenance. Cheeses differed mainly for secondary
      proteolysis, as shown by the principal component analysis applied to reversed
      phase fast protein liquid chromatography data of the pH 4.6-soluble fractions and
      by determination of the free AA. A total of 113 volatile components were
      identified in the Italian Pecorino cheeses by solid-phase microextraction coupled
      with gas chromatography-mass spectrometry analysis. The volatile profiles of the
      9 cheeses differed significantly. Quantitatively, alcohols were the most abundant
      chemical class for some cheeses, whereas ketones were the most abundant for other
      cheeses. Esters and carboxylic acids were largely found. Specific volatile
      components seemed to distinguish specific cheeses.

PMID- 17033000
TI  - Cheese pH, protein concentration, and formation of calcium lactate crystals.
AB  - The occurrence of calcium lactate crystals (CLC) in hard cheeses is a continual
      expense to the cheese industry, as consumers fail to purchase cheeses with this
      quality defect. This research investigates the effects of the protein
      concentration of cheese milk and the pH of cheese on the occurrence of CLC.
      Atomic absorption spectroscopy was used to determine total and soluble calcium
      concentrations in skim milk (SM1, 8.7% total solids), and skim milk supplemented
      with nonfat dry milk (CSM1, 13.5% total solids). Calcium, phosphorus, lactic
      acid, and citrate were determined in cheeses made with skim milk (SM2, 3.14%
      protein), skim milk supplemented with ultrafiltered milk (CSM2, 6.80% protein),
      and nonfat dry milk (CSM3, 6.80% protein). Supplementation with nonfat dry milk
      increased the initial total calcium in CSM1 (210 mg/100 g of milk) by 52%
      compared with the total calcium in SM1 (138 mg/100 g of milk). At pH 5.4, soluble
      calcium concentrations in CSM1 were 68% greater than soluble calcium in SM1. In
      cheeses made from CSM2 and CSM3, total calcium was 26% greater than in cheeses
      made from SM2. As the pH of cheeses made from SM2 decreased from 5.4 to 5.1, the
      concentration of soluble calcium increased by 61.6%. In cheeses made from CSM2
      and CSM3, the concentrations of soluble calcium increased by 41.4 and 45.5%,
      respectively. Calcium lactate crystals were observed in cheeses made from SM2 at
      and below pH 5.1, whereas CLC were observed in cheeses from CSM2 and CSM3 at and
      below pH 5.3. The increased presence of soluble calcium can potentially cause CLC
      to occur in cheese manufactured with increased concentrations of milk solids,
      particularly at and below pH 5.1.

PMID- 17033001
TI  - Detection and quantification of capsular exopolysaccharides from Streptococcus
      thermophilus using lectin probes.
AB  - The aim of this work was to use fluorescently labeled lectins to develop a
      convenient and reliable method to determine the relative abundance of capsular
      polysaccharides (CPS) at the surface of Streptococcus thermophilus MR-1C cells.
      Fluorescein isothiocyanate-labeled peanut agglutinin isolated from Arachis
      hypogaea was found to interact specifically with the CPS of Strep. thermophilus
      MR-1C. This labeled lectin was then used as an effective probe to detect and
      quantify CPS. A fluorescence-based lectin-binding assay was successfully applied
      to follow the accumulation of CPS during the growth of Strep. thermophilus MR-1C
      in milk and in M17 broth supplemented with lactose. Our results showed that in
      both media, CPS production by Strep. thermophilus MR-1C began during the
      exponential phase of growth and continued for several hours after the culture
      reached the stationary growth phase.

PMID- 17033002
TI  - Evaluation of environmental sampling and culture to determine Mycobacterium avium
      subspecies paratuberculosis distribution and herd infection status on US dairy
      operations.
AB  - The objectives of this study were to determine the distribution of Mycobacterium
      avium subspecies paratuberculosis (MAP) in the environment and assess the
      relationship between the culture status of MAP in the farm environment and herd
      infection status. The National Animal Health Monitoring System's Dairy 2002 study
      surveyed dairy operations in 21 states. One component of the study involved
      collection and culturing of environmental samples for MAP from areas on farms
      where manure accumulated from a majority of a herd's cows. Operations were
      selected for inclusion based on perceived risk factors for MAP infection
      identified in a previously administered questionnaire. Individual animal and
      environmental samples were collected and used to determine the efficiency of
      environmental sampling for determination of herd infection status. Individual
      animal fecal, serum, and milk samples were used to classify herds as infected or
      not infected based on the presence of at least one test-positive animal in the
      herd. A total of 483 environmental samples (approximately 5 per farm) were
      collected, and 218 (45.1%) were culture-positive for MAP. A similar percentage of
      environmental cultures collected from all designated areas were positive [parlor
      exits (52.3%), floors of holding pens (49.1%), common alleyways (48.8%), lagoons
      (47.4%), manure spreaders (42.3%), and manure pits (41.5%)]. Of the 98 operations
      tested with the environmental sample culture, 97 had individual serum ELISA
      results, 60 had individual fecal culture results, and 34 had individual milk
      ELISA results. Sixty-nine of the 98 operations (70.4%) had at least one
      environmental sample that was culture-positive. Of the 50 herds classified as
      infected by fecal culture, 38 (76.0%) were identified by environmental culture.
      Two of the 10 operations classified as not infected based on individual animal
      fecal culture were environmental culture-positive. Of the 80 operations
      classified as infected based on serum ELISA-positive results, 61 (76.3%) were
      identified as environmental-positive, whereas 20 of the 28 (71.4%) operations
      identified as infected based on milk ELISA were detected by environmental
      sampling. Environmental sample culturing is less costly than individual animal
      sampling, does not require animal restraint, and identified more than 70% of
      infected operations. Environmental sampling is another diagnostic tool that
      veterinarians and dairy producers can use to determine herd infection status for
      MAP.

PMID- 17033003
TI  - Short communication: Regulation of milk fat yield and fatty acid composition by
      insulin.
AB  - Diet-induced milk fat depression in dairy cows has been known for many years and
      several theories have been proposed. One that continues to receive support is the
      glucogenic-insulin theory. Previous studies testing this theory using a
      hyperinsulinemic-euglycemic clamp have had variable results attributable to
      variability in the use of body fat reserves as a source of milk fatty acids. Our
      objective was to test the glucogenic-insulin theory using cows immediately
      postpartum, a period when the use of body fat for milk fat synthesis is greatest.
      During wk 2 postpartum, 5 cows were given a 2-d baseline period and then clamped
      for 4 d. Insulin was increased more than 2-fold during the clamp while the blood
      glucose concentration was maintained. Milk yield was not altered by
      administration of the clamp (38.7 vs. 39.0 +/- 1.4 kg/d); however, the milk fat
      percentage and yield were reduced by 27% and plasma nonesterified fatty acids
      were reduced by 68%. Analysis of the milk fatty acid composition revealed that
      the decrease in milk fat yield during use of the clamp was almost exclusively due
      to reductions in preformed fatty acids; this is the exact opposite of what is
      observed with diet-induced milk fat depression. Therefore, our results do not
      support the glucogenic-insulin theory of diet-induced milk fat depression. The
      results further indicated that reductions in milk fat observed previously with
      hyperinsulinemic-euglycemic clamps or with glucose or propionate infusions were
      most likely consequences of the ability of insulin to inhibit lipolysis, thereby
      limiting the mammary availability of preformed fatty acids mobilized from body
      reserves.

PMID- 17033004
TI  - Milking frequency, estradiol cypionate, and somatotropin influence lactation and
      reproduction in dairy cows.
AB  - Our objectives were to determine lactational and reproductive outcomes in
      response to increased milking frequency (MF), injection of estradiol cypionate
      (ECP), and treatment with bovine somatotropin (bST). Lactating dairy cows (n =
      144) were blocked by lactation number (1 vs. 2+) and assigned randomly to a 2 x 2
      x 2 factorial experiment consisting of 8 treatment combinations: 1) MF consisting
      of 4x daily milking (4x) for the first 30 d in milk (DIM) vs. 2x daily milking
      (2x), with all cows milked 2x after 30 DIM; 2) 10 mg of ECP given postpartum at 8
      +/- 3 DIM versus controls that received ECP diluent (oil); and 3) biweekly bovine
      somatotropin (bST), starting sometime after 60 DIM, versus no bST. Ovulation
      before the first artificial insemination was synchronized by using Heatsynch
      (GnRH injection 7 d before PGF2alpha followed in 24 h by ECP), and cows were
      artificially inseminated after detected estrus or at 48 h after ECP, whichever
      came first. Pregnancy was assessed by transrectal ultrasonography 28 to 30 d
      after artificial insemination. Daily yield and weekly components of milk were
      measured during the first 90 DIM. Intervals to first and second postpartum
      ovulation were unaffected by treatment, but cows were in estrus earlier after 2x
      (24 +/- 4 d) than 4x (41 +/- 4 d) daily MF, and sooner after ECP (25 +/- 3 d)
      than after oil (39 +/- 4 d) treatment. Pregnancy rates among 4x cows increased
      for ECP versus oil (52.8 vs. 27.8%) more than for cows with 2x MF treated with
      ECP versus oil (50.0 vs. 39.4%). Increased MF increased daily milk yields and
      energy-corrected milk yields during the first 30 DIM. Although milk yields were
      increased acutely by ECP during the 10 d after its injection, subsequent milk
      yields were decreased for ECP-treated cows previously milked 4x daily. Treatment
      with bST increased overall daily milk yields most in cows previously milked 2x
      daily and treated with oil and those milked 4x daily and treated with ECP. We
      concluded that early postpartum ECP injection increased pregnancy rates, but
      generally had detrimental effects on milk yields after 30 DIM for ECP-treated
      cows previously milked 4x daily, unless those cows also were treated with bST.

PMID- 17033005
TI  - Effect of cis-urocanic acid on bovine neutrophil generation of reactive oxygen
      species.
AB  - Neutrophils play a fundamental role in the host innate immune response during
      mastitis and other bacterial-mediated diseases of cattle. One of the critical
      mechanisms by which neutrophils contribute to host innate immune defenses is
      through their ability to phagocytose and kill bacteria. The ability of
      neutrophils to kill bacteria is mediated through the generation of reactive
      oxygen species (ROS). However, the extracellular release of ROS can be
      deleterious to the host because ROS induce tissue injury. Thus, in diseases such
      as mastitis that are accompanied by the influx of neutrophils, the generation of
      large quantities of ROS may result in significant injury to the mammary
      epithelium. cis-Urocanic acid (cis-UCA), which is formed from the UV
      photoisomerization of the trans isoform found naturally in human and animal skin,
      is an immunosuppressive molecule with anti-inflammatory properties. Little is
      known about the effect of cis-UCA on neutrophils, although one report
      demonstrated that it inhibits human neutrophil respiratory burst activity.
      However, the nature of this inhibition remains unknown. Because of the potential
      therapeutic use that a molecule such as cis-UCA may have in blocking excessive
      respiratory burst activity that may be deleterious to the host, the ability of
      cis-UCA to inhibit bovine neutrophil production of ROS was studied. Further,
      because neutrophil generation of ROS is necessary for optimal neutrophil
      bactericidal activity, a response which is critical for the host innate immune
      defense against infection, the effects of cis-UCA on bovine neutrophil
      phagocytosis and bacterial killing were assayed. cis-Urocanic acid dose
      dependently inhibited the respiratory burst activity of bovine neutrophils as
      measured by luminol chemiluminescence. Subsequently, the effect of cis-UCA on the
      production of specific oxygen radicals was investigated using more selective
      assays. Using 2 distinct assays, we established that cis-UCA inhibited the
      generation of extracellular superoxide. In contrast, cis-UCA had no effect on the
      generation of intracellular levels of superoxide or other ROS. At concentrations
      that inhibited generation of extracellular superoxide, bovine neutrophil
      phagocytosis and bacterial activity remained intact. Together, these data suggest
      that cis-UCA inhibits the tissue-damaging generation of extracellular ROS while
      preserving neutrophil bactericidal activity.

PMID- 17033006
TI  - Short communication: In vitro antimicrobial susceptibility of Prototheca
      wickerhamii and Prototheca zopfii isolated from bovine mastitis.
AB  - Bovine mastitis caused by Prototheca spp. can assume high significance because of
      economic losses and the potential risk to public health. Studies on the
      susceptibility of Prototheca spp. to antimicrobials have demonstrated its high
      level of resistance. We report the susceptibility of bovine isolates of
      Prototheca wickerhamii and Prototheca zopfii to amphotericin B and nystatin, 2
      antifungal agents commonly used in the control of protothecosis, and discuss the
      results. After subculture, minimum inhibitory concentrations of both antifungal
      drugs were determined using macrodilution and agar diffusion methods. The
      inoculum concentration was standardized by determination of colony-forming units
      per milliliter. Nystatin showed more efficacy than amphotericin B in inhibiting
      P. wickerhamii growth. In contrast, growth inhibition of P. zopfii was similar
      for both antifungal agents. This study demonstrates different in vitro
      susceptibility patterns of P. wickerhamii and P. zopfii, reinforcing the
      necessity for more investigation into drugs that can be used with clinical
      efficacy.

PMID- 17033008
TI  - Omitting the dry-off period negatively affects colostrum and milk yield in dairy
      goats.
AB  - Seventeen pregnant multiparous Murciano-Granadina dairy goats, kept in a semi
      intensive exploitation system with once daily milking throughout lactation and 1
      kidding per year (milk yield, 577 L/300 d), were used to study the effects of dry
      off period length on performance during the subsequent lactation. Goats were
      mated at wk 29 of lactation and were assigned to 2 experimental groups according
      to dry-off treatment: goats that were dried off 56 d before expected kidding
      (D56; n = 9) and goats without dry-off (D0; n = 8). After parturition, kids were
      removed from their mothers and weighed before suckling. Goats were hand milked to
      obtain colostrum and were machine milked thereafter. Colostrum was sampled for
      composition and IgG analysis. Milk yield was recorded weekly during the preceding
      and subsequent lactations. Udders were biopsied in a sample of goats at d -65
      (late lactation), d -49 (during dry-off), and d 48 (early lactation) to kidding
      (d 0). Apoptotic and proliferating cells in mammary tissues were detected
      immunohistochemically. Five goats (63%) in the D0 group dried off spontaneously
      at 27 +/- 4 d before kidding and were considered separately (D27). The rest of
      the D0 goats yielded 0.86 L/d from d -56 to kidding. Goats kidded 2.25 kids/goat,
      but the D0 kids had smaller birth weights (1.7 kg) than the D27 (2.2 kg) and D56
      (2.1 kg) kids. Colostrum of the D0 goats contained less IgG (5.6 mg/mL) than the
      D27 (32.9 mg/mL) and the D56 (42.4 mg/mL) goats. In the subsequent lactation (210
      d), the D0 goats produced less milk (1.78 L/d) than the D27 (2.51 L/d) and D56
      (2.24 L/d) goats, with no detectable difference between the D27 and D56 goats.
      Apoptosis and proliferation indices increased from 0.51 and 2.09%, at d -65, to
      1.75 and 7.12% at d -49 (d 7 of dry-off) in D56 goats. Despite differences in
      daily milk yield during early lactation (d 48) between the D0, D27, and D56
      treatments (1.73, 2.68, and 2.53 L/d, respectively), no differences in apoptosis
      or proliferation indices were detected (D0: 0.65 and 2.48%; D27: 0.68 and 1.37%;
      and D56: 0.71 and 2.95%), indicating that duration of the dry period did not
      affect mammary cell turnover during the subsequent lactation. Omitting the dry
      period between lactations reduced the quality of colostrum and had negative
      effects on milk yield in dairy goats. Goats dried off spontaneously for 27 d were
      as productive as goats dried off for 56 d, indicating that less than 2 mo of dry
      off may be sufficient in practice.

PMID- 17033007
TI  - Reproduction in dairy cows following progesterone insert presynchronization and
      resynchronization protocols.
AB  - The objectives of this study were to evaluate the effects of an intravaginal
      insert containing progesterone (CIDR, controlled internal drug releasing)
      administered in presynchronization and resynchronization protocols on cyclicity,
      detection of estrus, pregnancy rate, and pregnancy loss to first AI;
      reinsemination patterns; and pregnancy rates to second postpartum AI before and
      after the time of first-service pregnancy diagnosis in dairy cows. Holstein cows
      (n = 1,052) were blocked by parity and BCS at 3 +/- 3 d in milk (study d 0 = day
      of calving) and assigned randomly to 1 of 3 presynchronization treatments. During
      the presynchronization programs, all cows received 2 injections of PGF2alpha, on
      study d 35 and 49. Cows enrolled in the control presynchronization treatment
      received AI after detected estrus from study d 49 to 62. Cows enrolled in the
      CIDR estrus-detection (CED) presynchronization treatment received a CIDR insert
      from study d 42 to 49 and AI on detection of estrus from d 49 to 62. Cows
      enrolled in the CIDR timed AI (CTAI) presynchronization treatment received the
      same treatment as CED, but were subjected to timed AI on study d 72 after the
      Ovsynch (GnRH, 7 d PGF2alpha, 2 d GnRH, 24 h timed AI) protocol. The control and
      CED cows not inseminated by study d 62 were enrolled in the Ovsynch protocol on
      the same day and received timed AI on study d 72. After first AI, cows were
      assigned to no resynchronization (RCON) or resynchronization with a CIDR insert
      (RCIDR) between 14 and 21 d after AI. Blood samples collected on study d 35, 49,
      and 62 were analyzed for concentrations of progesterone and cows were classified
      as anestrous when progesterone was < 1.0 ng/mL in the first 2 samples. On study d
      62, anestrous cows with progesterone > or = 1.0 ng/mL were classified as having
      resumed cyclicity. Pregnancy was diagnosed at 31 and 60 d after first AI and at
      42 d after second AI. A greater proportion of anestrous cows in CED and CTAI
      became cyclic by d 62 postpartum than control cows. Resynchronization with the
      CIDR insert increased the pregnancy rate at 31 d after first AI in CED and CTAI,
      and at 60 d after AI in all cows because of reduced pregnancy loss. These results
      indicate that presynchronization with the CIDR insert increased induction of
      cyclicity in anestrous cows and that resynchronization with the CIDR insert did
      not affect the reinsemination rate but did reduce pregnancy loss and increased
      the pregnancy rate at 60 d after first AI.

PMID- 17033009
TI  - Risk factors associated with Cryptosporidium infection on dairy farms in a New
      York State watershed.
AB  - A cross-sectional study was carried out to determine the prevalence of
      Cryptosporidium parvum-like oocyst shedding on dairy farms in a watershed in New
      York State and to identify the factors that put animals at risk. A proportional
      sample of dairy herds in the targeted area was obtained, and animals were
      selected using a stratified sampling design to ensure representation of the
      population at risk. Fecal samples were collected per rectum and analyzed for the
      presence of C. parvum-like oocysts using the quantitative centrifugation
      concentration flotation technique and a proprietary enzyme-linked immunoassay.
      Additionally, isolates of Cryptosporidium were examined via bidirectional DNA
      sequencing. Data on putative risk factors were collected at the time of sampling
      and analyzed for association using logistic regression. The herd prevalence was
      42% and the overall animal prevalence was 3.2%. The prevalence among animals less
      than 60 d of age was 20%. The likelihood of shedding Cryptosporidium decreased
      with the age of the animal and varied with the type of barn water source. Both
      the number of unweaned calves present at the time of the study, and whether the
      calves were tied vs. not tied increased the risk of infection. There was
      significant agreement between the flotation and PCR techniques. Sequencing
      revealed that 50% of the isolates were Cryptosporidium bovis, an isolate thought
      to be nonzoonotic.

PMID- 17033010
TI  - Treatment with gonadotropin-releasing hormone after first timed artificial
      insemination improves fertility in noncycling lactating dairy cows.
AB  - Lactating Holstein cows were assigned randomly to treatments to improve fertility
      after first postpartum timed artificial insemination (TAI). In Experiment 1, cows
      received no treatment (control; n = 9), a controlled internal drug releasing
      (CIDR) insert from 5 to 12 d after TAI (CIDR; n = 9), or 100 microg of GnRH 5 d
      after TAI (G5; n = 7). Although treatments did not affect circulating
      progesterone (P4) concentrations from 5 to 19 d after TAI, there was a tendency
      for CIDR cows to have greater P4 compared with control or G5 cows within 24 h
      after treatment. In 2 field trials, cows received either control (n = 223), CIDR
      (n = 218), or G5 (n = 227) treatments (Experiment 2), or control (n = 160), G5 (n
      = 159), or treatment with 100 microg of GnRH 7 d after TAI (G7; n = 163;
      Experiment 3). Treatment did not affect pregnancies per AI (P/AI) in Experiments
      2 or 3; however, when data were combined to compare control (n = 383) and G5 (n =
      386) treatments, P/AI tended to be greater for G5 (49.1%) than for control
      (45.8%) cows. This effect resulted from a GnRH treatment x cyclicity status
      interaction in which P/AI for noncycling cows receiving G5 was greater than for
      noncycling control cows (45.5 vs. 31.1%). In conclusion, treatment with CIDR
      inserts after TAI had no effect on P/AI, whereas treatment with GnRH 5 d after
      TAI improved P/AI for noncycling, but not for cycling cows.

PMID- 17033011
TI  - Importance of the sampled milk fraction for the prediction of total quarter
      somatic cell count.
AB  - This study investigated the changes in somatic cell counts (SCC) in different
      fractions of milk, with special emphasis on the foremilk and cisternal milk
      fractions. Therefore, in Experiment 1, quarter milk samples were defined as
      strict foremilk (F), cisternal milk (C), first 400 g of alveolar milk (A1), and
      the remaining alveolar milk (A2). Experiment 2 included 6 foremilk fractions (F1
      to F6), consisting of one hand-stripped milk jet each, and the remaining
      cisternal milk plus the entire alveolar milk (RM). In Experiment 1, changes
      during milking indicated the importance of the sampled milk fraction for
      measuring SCC because the decrease in the first 3 fractions (F, C, and A1) was
      enormous in milk with high total quarter SCC. The decline in SCC from F to C was
      50% and was 80% from C to A1. Total quarter SCC presented a value of
      approximately 20% of SCC in F or 35% of SCC in C. Changes in milk with low or
      very low SCC were marginal during milking. Fractions F and C showed significant
      differences in SCC among different total SCC concentrations. These differences
      disappeared with the alveolar fractions A1 and A2. In Experiment 2, a more
      detailed investigation of foremilk fractions supported the findings of Experiment
      1. A significant decline in the foremilk fractions even of F1 to F6 was observed
      in high-SCC milk at concentrations >350 x 10(3) cells/mL. Although one of these
      foremilk fractions presented only 0.1 to 0.2% of the total milk, the SCC was 2-
      to 3-fold greater than the total quarter milk SCC. Because the trait of interest
      (SCC) was measured directly by using the DeLaval cell counter (DCC), the quality
      of measurement was tested. Statistically interesting factors (repeatability,
      recovery rate, and potential matrix effects of milk) proved that the DCC is a
      useful tool for identifying the SCC of milk samples, and thus of grading udder
      health status. Generally, the DCC provides reliable results, but one must
      consider that SCC even in strict foremilk can differ dramatically from SCC in the
      total cisternal fraction, and thus also from SCC in the alveolar fraction.

PMID- 17033012
TI  - Effect of rubber flooring on claw health in lactating dairy cows housed in free
      stall barns.
AB  - Multiparous dairy cows between 10 to 30 d in milk (DIM) were enrolled in a
      clinical trial to evaluate the effects of rubber flooring on the development of
      claw lesions, locomotion scores, clinical lameness, and rates of hoof growth and
      wear. Two groups of cows were housed in identical free-stall facilities, except
      that 1 pen (rubber, n = 84) had rubber alley mats covering the entire concrete
      floor of the pen, whereas cows in the second pen were exposed to concrete
      flooring (concrete, n = 82) without rubber alley mats. All cows were evaluated 3
      times between 10 and 30, 74 and 94, and 110 and 130 DIM for 1) the presence of
      claw lesions on their rear feet, 2) the occurrence of clinical lameness based on
      a locomotion score, and 3) rates of claw growth and wear as observed on the
      dorsal wall of the right lateral claw. No differences between flooring groups at
      the time of enrollment were detected for lactation number, mean DIM at first
      examination, body condition score, and proportion of cows with claw lesions at
      the first examination. Odds of developing claw lesions between examinations were
      not different for cows exposed to the rubber surface compared with those exposed
      to concrete. Cows on concrete, however, had greater odds of developing or
      exacerbating existing heel erosion than cows on rubber flooring. Regardless of
      the flooring surface, the lateral claw was more likely to develop lesions than
      the medial claw. Odds of becoming lame by the third examination and the
      proportion of cows requiring therapeutic hoof trimming because of lameness were
      greater for concrete-exposed cows than those on rubber. Cows on rubber flooring
      had decreased claw growth and wear between the first and last examination
      compared with cows on concrete. Regardless of flooring surface, second-lactation
      cows had greater wear rates than those in third or greater parities. Results of
      our study suggest that a soft flooring surface, such as interlocking rubber, is
      beneficial for hoof health.

PMID- 17033013
TI  - Housing system, milk production, and zero-grazing effects on lameness and leg
      injury in dairy cows.
AB  - The aim of this study was to assess the effect of grazing (G) vs. zero-grazing
      (ZG), level of milk production, and quality and type of housing system [free
      stalls (FS) and straw yards (SY)] on the prevalence of lameness and leg injuries
      in dairy cows. Observations were made on 37 commercial dairy farms across Great
      Britain. A single visit of 5 d duration was made to each farm. During this visit,
      lameness scores and the incidence of swellings, rubs, and injuries to hocks and
      knees were recorded on all the peak- or mid-lactation cows. Aspects of the
      quality of housing and management that were likely to affect foot and leg health
      were recorded. There were more lame cows on ZG farms (39 +/- 0.02%) than on
      grazing (G) farms (15 +/- 0.01%), and lameness scores were higher on FS farms
      compared with SY farms (0.25 +/- 0.01 vs. 0.05 +/- 0.01). Cows on SY farms had
      fewer hock and knee injuries compared with FS farms. The frequency of knee
      swellings was higher on ZG farms (0.31 +/- 0.02) than on G farms (0.15 +/- 0.01).
      Aspects of the free-stall design affected foot and leg health. The number of hock
      swellings increased with increasing stall gradient (0.16 +/- 0.01 with no slope
      vs. 0.39 +/- 0.02 at a 0 to 1.5% slope). There was an interaction between the
      length of the free-stall lunging space and the hip width of the cow, indicating
      that the incidence of lameness is generally highest on farms with small free
      stalls and heavy cows. High levels of milk production did not affect lameness or
      leg injury. The results indicate that housing cows throughout the year
      potentially has a detrimental effect on foot and leg health. However, good free
      stall design may reduce lameness and leg lesions.

PMID- 17033014
TI  - Comparison of models to identify lame cows based on gait and lesion scores, and
      limb movement variables.
AB  - Bovine lameness results in pain and suffering in cattle and economic loss for
      producers. A system for automatically detecting lame cows was developed recently
      that measures vertical force components attributable to individual limbs. These
      measurements can be used to calculate a number of limb movement variables. The
      objective of this investigation was to explore whether gait scores, lesion
      scores, or combined gait and lesion scores were more effectively captured by a
      set of 5 limb movement variables. A set of 700 hind limb examinations was used to
      create gait-based, lesion-based, and combined (gait- and lesion-based) models.
      Logistic regression models were constructed using 1, 2, or 3 d of measurements.
      Resulting models were tested on cows not used in modeling. The accuracy of lesion
      score models was superior to that of gait-score models; lesion-based models
      generated greater values of areas under the receiving operating characteristic
      curves (range 0.75 to 0.84) and lower mean-squared errors (0.13 to 0.16) compared
      with corresponding values for the gait-based models (0.63 to 0.73 and 0.26 to
      0.31 for receiving operating characteristic and mean-squared errors,
      respectively). These results indicate that further model development and
      investigation could generate automated and objective methods of lameness
      detection in dairy cattle.

PMID- 17033015
TI  - Effects of body weight and nutrition on mammary protein expression profiles in
      Holstein heifers.
AB  - A proteomics approach was used to characterize biochemical and cellular
      mechanisms governing effects of peripubertal feeding on heifer mammary
      development. Mammary parenchymal tissue from 24 Holstein heifers randomly
      assigned to treatments arranged in a 2 x 2 factorial design was used to generate
      2-dimensional protein maps of mammary tissue extracts. Heifers were reared on 1
      of 2 dietary treatments, restricted (650 g/ d of daily gain) or elevated (950 g/d
      of daily gain) and killed at 1 of 2 body weights (BW, 200 or 350 kg). Cytosolic
      mammary gland extracts were prepared from frozen mammary parenchyma. Proteome
      maps of extracts were constructed using PDQuest software. Densities of 820
      protein spots were analyzed using the MIXED procedure of SAS. Protein spots were
      characterized by changes in profiles of expression in response to increased BW,
      dietary treatment, or both. Dietary treatment influenced the expression of 131
      protein spots, whereas heifer BW influenced the expression of 108 spots. The 22
      most highly influenced (statistically) spots were excised and submitted for mass
      spectrometric analyses. Returned protein names and accession numbers were used in
      National Center for Biotechnology Information database searches to obtain
      information on the identified proteins. For example, one of the proteins that
      differed by dietary treatment, transferrin, a binding protein of insulin-like
      growth factor binding protein-3, was identified via these methods. Possible roles
      of this and other proteins in mammary development are described. We concluded
      that a proteomic approach is an effective tool for identifying the proteins
      involved in bovine mammary development.

PMID- 17033016
TI  - Developmental and nutritional regulation of the prepubertal heifer mammary gland:
      I. Parenchyma and fat pad mass and composition.
AB  - Prior to puberty, elevated nutrient intake has been shown to negatively affect
      prepubertal mammary development in the heifer. The objective of this study was to
      evaluate the effects of increased nutrient intake on mammary development in
      Holstein heifers at multiple body weights from birth through puberty.
      Specifically, this study evaluated the effects of nutrient intake and body weight
      at harvest on 1) total weight and DNA content of the parenchyma (PAR) and mammary
      fat pad (MFP) and 2) PAR and MFP composition. Starting at 45 kg of body weight,
      heifers (n = 78) were assigned to either a restricted (R) or elevated (E) level
      of nutrient intake supporting 650 (R) or 950 (E) g/d of body weight gain. Heifers
      were harvested at 50-kg increments from 100 to 350 kg of body weight. Mammary fat
      pad weight and DNA content were greater in E- than in R-heifers. Additionally, E
      heifers had a greater fraction of lipids and a smaller fraction of protein in
      their MFP than did R-heifers. Parenchyma weight and DNA were lower in E- than in
      R-heifers; however, when analyzed with age as a covariate term, treatment was no
      longer a significant term in the model. Level of nutrient intake had no effect on
      the lipid, protein, or hydroxyproline composition of the PAR. Collectively, these
      data demonstrate that PAR is refractory to the level of nutrient intake whereas
      MFP is not. Furthermore, the covariate analysis demonstrated that age at harvest,
      not the level of nutrient intake, was the single greatest determinant of total
      PAR DNA content.

PMID- 17033017
TI  - Developmental and nutritional regulation of the prepubertal bovine mammary gland:
      II. Epithelial cell proliferation, parenchymal accretion rate, and allometric
      growth.
AB  - It is well documented that elevated nutrient intake prior to puberty reduces
      prepubertal mammary development in the bovine. The companion paper demonstrated
      that age at harvest is a primary determinant of parenchymal (PAR) mass and that
      any effects of elevated energy intake on mechanisms regulating mammary
      development are dwarfed by this effect of time. Therefore, it is hypothesized
      that while causing a decrease in prepubertal PAR mass, elevated nutrient intake
      will have no effect on growth characteristics of the mammary gland. The
      objectives of this experiment were to evaluate the effects of increased nutrient
      intake from early in life on 1) mammary epithelial cell proliferation, 2) mammary
      PAR DNA accretion rates, and 3) the dynamics of prepubertal allometric PAR
      growth. Holstein heifers (n = 78) were fed from 45 kg of body weight either
      elevated (E) or restricted (R) levels of nutrients to support 950 (E) or 650 (R)
      g/d of body weight gain. Six heifers per treatment were harvested at 50-kg
      increments from 100 to 350 kg of body weight. Heifers on the E plane of nutrition
      had higher plasma leptin and less PAR DNA than their body weight-matched R-intake
      cohorts. Despite this reduction in PAR DNA, treatment did not negatively
      influence mammary epithelial cell proliferation or the PAR DNA accretion rate.
      Dynamics of allometric and isometric mammary growth were also unaffected by the
      level of nutrient intake, as was exit from allometric growth. This work
      represents the first demonstrating that the level of nutrient intake and the
      concomitant increase in plasma leptin have no measurable influence on 1) the rate
      of PAR DNA accretion, 2) mammary epithelial cell proliferation, or 3) total PAR
      mass and, by default, the local or systemic controls that coordinate these
      processes.

PMID- 17033018
TI  - Feeding a low manganese diet to heifers during gestation impairs fetal growth and
      development.
AB  - A study was conducted to examine the effects of low dietary Mn on growth
      performance of pregnant heifers and fetal development of their offspring. Twenty
      pregnant Angus (n = 9) and Simmental (n = 11) heifers averaging 17 mo of age and
      447.6 kg of initial body weight were used in the 267-d study. Heifers were
      selected from a previous study examining the effects of supplemental Mn on growth
      and reproductive performance of heifers. Ten pregnant heifers per treatment from
      the control (analyzed at 15.8 mg of Mn/kg of DM) and supplemental Mn (50 mg/kg of
      DM) treatments were randomly selected at the conclusion of the previous study to
      continue on their respective dietary treatments through gestation and early
      lactation. Serum cholesterol for the 267-d period was not affected by treatment.
      Whole-blood Mn concentration of heifers on d 267 was not affected by treatment.
      Whole-blood Mn concentration at birth was lower in calves born to control heifers
      than in those born to supplemented heifers. Calves born to control heifers
      weighed less at birth than those born to heifers receiving supplemental Mn.
      Calves born to control heifers suffered from varying signs of Mn deficiency,
      including superior brachygnathism, unsteadiness, disproportionate dwarfism, and
      swollen joints. Results suggest that feeding gestating heifers a diet containing
      16.6 mg of Mn/kg of DM is not adequate for proper fetal development.
      Supplementation of 50 mg of Mn/kg of DM to the control diet was sufficient to
      overcome any signs of Mn deficiency in calves.

PMID- 17033019
TI  - Effect of feeding frequency of a total mixed ration on the performance of high
      yielding dairy cows.
AB  - Forty Finnish Ayrshire cows, 16 primiparous and 24 multiparous, were randomly
      assigned to 1 of 2 treatments (FF1 or FF5). Total mixed ration (TMR) was fed once
      a day on the FF1 treatment and 5 times a day on the FF5 treatment. The experiment
      began at calving and continued to wk 28 of lactation. The TMR consisted of a
      grass silage and concentrate mix. The amount of concentrate in the TMR was 51% on
      a DM basis. The feeding frequency had no effect on milk or energy-corrected milk
      yields or on milk composition. The average energy-corrected milk yield was 32.8
      kg/d on the FF1 treatment and 32.5 kg/d on the FF5 treatment. The less frequent
      feeding increased the dry matter intake (DMI) of cows. The average DMI during the
      experiment was 20.9 kg/d on the FF1 treatment and 19.9 kg/d on the FF5 treatment.
      The difference in DMI was due to the differences in DMI of the mature cows.
      Energy and protein conversion tended to be lower with feeding once a day compared
      with feeding 5 times a day. The cows' feeding behavior was also observed. Cows
      fed 5 times a day tended to eat quite evenly after each delivery, whereas on the
      FF1 treatment there were 2 clear feeding peaks in the evening after the feed
      delivery. The time spent eating during the observation period was longer on FF5
      than on FF1. The cows fed once a day spent more time lying than the cows fed 5
      times a day. Based on the observations of feeding behavior, feeding a TMR 5 times
      a day seemed to be too frequent based on the increased restlessness and decreased
      lying time of the cows.

PMID- 17033020
TI  - Effect of barley and its amylopectin content on ruminal fermentation and nitrogen
      utilization in lactating dairy cows.
AB  - The effect of type of grain (corn vs. barley) and amylopectin content of barley
      grain (normal vs. waxy) on ruminal fermentation, digestibility, and utilization
      of ruminal ammonia nitrogen for milk protein synthesis was studied in a
      replicated 3 x 3 Latin square design trial with 6 lactating dairy cows. The
      experimental treatments were (proportion of dietary dry matter): CORN, 40% corn
      grain, NBAR, 30% normal Baronesse barley:10% corn grain, and WBAR, 30% high
      amylopectin (waxy) Baronesse barley:10% corn grain. All grains were steam-rolled
      and fed as part of a total mixed ration. The NBAR and WBAR diets resulted in
      increased ruminal ammonia concentrations compared with CORN (8.2, 7.4, and 5.6
      mM, respectively), but other ruminal fermentation parameters were not affected.
      Ruminal digestibility of dietary nutrients and microbial protein synthesis in the
      rumen were also not affected by diet. Corn grain had greater in situ effective
      ruminal dry matter degradability (62.8%) than the barley grains (58.2 and 50.7%,
      respectively), and degradability of the normal barley starch was greater than
      that of the waxy barley (69.3 and 58.9%, respectively). A greater percentage of
      relative starch crystallinity was observed for the waxy compared with the normal
      barley grain. Total tract apparent digestibility of dry matter and organic matter
      were decreased by WBAR compared with CORN and NBAR. Total tract starch
      digestibility was greater and milk urea nitrogen content was lower for CORN
      compared with the 2 barley diets. In this study, the extent of processing of the
      grain component of the diet was most likely the factor that determined the diet
      responses. Minimal processing of barley grain (processing indexes of 79.2 to
      87.9%) reduced its total tract digestibility of starch compared with steam-rolled
      corn (processing index of 58.8%). As a result of the increased ammonia
      concentration and reduced degradability of barley dry matter in the rumen, the
      utilization of ruminal ammonia nitrogen for microbial protein synthesis was
      decreased with the barley diets compared with the corn-based diet. In this study,
      waxy Baronesse barley was less degradable in the rumen and the total digestive
      tract than its normal counterpart. The most likely reasons for these effects were
      the differences in starch characteristics and chemical composition, and perhaps
      the different response to processing between the 2 barleys.

PMID- 17033021
TI  - Short communication: Eicosatrienoic acid and docosatrienoic acid do not promote
      vaccenic acid accumulation in mixed ruminal cultures.
AB  - Previous research found that docosahexaenoic acid (C22:6n-3) was a component of
      fish oil that promotes trans-C18:1 accumulation in ruminal cultures when
      incubated with linoleic acid. The objective of this study was to determine if
      eicosatrienoic acid (C20:3n-3) and docosatrienoic acid (C22:3n-3), n-3 fatty
      acids in fish oil, promote accumulation of trans-C18:1, vaccenic acid (VA) in
      particular, using cultures of mixed ruminal microorganisms. Treatments consisted
      of control, control plus 5 mg of C20:3n-3 (ETA), control plus 5 mg of C22:3n-3
      (DTA), control plus 15 mg of linoleic acid (LA), control plus 5 mg of C20:3n-3
      and 15 mg of linoleic acid (ETALA), and control plus 5 mg of C22:3n-3 and 15 mg
      of linoleic acid (DTALA). Treatments were incubated in triplicate in 125-mL
      flasks, and 5 mL of culture contents was taken at 0 and 24 h for fatty acid
      analysis by gas-liquid chromatography. After 24 h of incubation, the
      concentrations of trans-C18:1 (0.87, 0.88, and 0.99 mg/culture), and VA (0.52,
      0.56, and 0.62 mg/culture) were similar for the control, ETA, and DTA cultures,
      respectively. The concentrations of trans-C18:1 (5.51, 5.41, and 5.36
      mg/culture), and VA (4.78, 4.62, and 4.59 mg/culture) were also similar between
      LA, ETALA, and DTALA cultures, respectively. These data suggest that C20:3n-3 and
      C22:3n-3 are not the active components in fish oil that promote VA accumulation
      when incubated with linoleic acid.

PMID- 17033022
TI  - Effect of casein and propionate supply on mammary protein metabolism in lactating
      dairy cows.
AB  - The effects of casein (CN) and propionate (C3) on mammary AA metabolism were
      determined in 3 multiparous Holstein cows fitted with both duodenal and ruminal
      cannulas and used in a replicated Youden square with six 14-d periods. Casein
      (743 g/d in the duodenum) and C3 (1,041 g/d in the rumen) infusions were tested
      in a factorial arrangement. For each period, L-[1-(13)C]Leu (d 11) and NaH[13C]O3
      (d 13) were infused into a jugular vein, and blood samples were taken from the
      carotid artery and the mammary vein to determine Leu kinetics and net uptake of
      AA. Both CN and C3 treatments separately increased milk protein concentration and
      yield. With CN there was a general response in mammary protein metabolism,
      involving increases in Leu net uptake (30%), the uptake:output ratio (8%),
      protein synthesis (11%), secretion in milk protein (21%), and oxidation (259%).
      In contrast, C3 treatments tended to increase only Leu in milk protein (7%) and,
      when in combination with CN, to reduce Leu used for protein synthesis (5%).
      Across all treatments, most Leu uptake by the mammary gland was accounted for as
      Leu in milk or oxidized, and the Leu balance was therefore achieved without
      involvement of either net peptide use or production. Mammary uptake of group 1 AA
      increased to match milk output with all infusions. In contrast, mammary uptake of
      group 2 AA exceeded output to a greater extent with CN than with C3 infusions,
      whereas the increment in uptake of group 3 AA increased with C3 treatments.
      Overall, these data suggest that different mechanisms operate to improve milk
      protein production when either protein or energy is supplied.

PMID- 17033023
TI  - Effects of addition of essential oils and monensin premix on digestion, ruminal
      fermentation, milk production, and milk composition in dairy cows.
AB  - Four ruminally cannulated, lactating Holstein cows were used in a 4 x 4 Latin
      square design (28-d periods) with a 2 x 2 factorial arrangement of treatments to
      study the effects of dietary addition of essential oils (0 vs. 2 g/d; EO) and
      monensin (0 vs. 350 mg/d; MO) on digestion, ruminal fermentation characteristics,
      milk production, and milk composition. Intake of dry matter averaged 22.7 kg/d
      and was not significantly affected by dietary additives. Apparent digestibilities
      of dry matter, organic matter, neutral detergent fiber, and starch were similar
      among treatments. Apparent digestibility of acid detergent fiber was increased
      when diets were supplemented with EO (48.9 vs. 46.0%). Apparent digestibility of
      crude protein was higher for cows fed MO compared with those fed no MO (65.0 vs.
      63.6%). Nitrogen retention was not changed by additive treatments and averaged
      27.1 g/d across treatments. Ruminal pH was increased with the addition of EO
      (6.50 vs. 6.39). Ruminal ammonia nitrogen (NH3-N) concentration was lower with MO
      supplemented diets compared with diets without MO (12.7 vs. 14.3 mg/100 mL). No
      effect of EO and MO was observed on total volatile fatty acid concentrations and
      molar proportions of individual volatile fatty acids. Protozoa counts were not
      affected by EO and MO addition. Production of milk and 4% fat-corrected milk was
      similar among treatments (33.6 and 33.4 kg/d, respectively). Milk fat content was
      lower for cows fed MO than for cows fed diets without MO (3.8 vs. 4.1%). The
      reduced milk fat concentration in cows fed MO was associated with a higher level
      of trans-10 18:1, a potent inhibitor of milk fat synthesis. Milk urea nitrogen
      concentration was increased by MO supplementation, but this effect was not
      apparent when MO was fed in combination with EO (interaction EO x MO). Results
      from this study suggest that feeding EO (2 g/d) and MO (350 mg/d) to lactating
      dairy cows had limited effects on digestion, ruminal fermentation
      characteristics, milk production, and milk composition.

PMID- 17033024
TI  - Effects of supplementing concentrates differing in carbohydrate composition in
      veal calf diets: I. Animal performance and rumen fermentation characteristics.
AB  - The aim of this experiment was to examine the effects of concentrates in feed,
      differing in carbohydrate source, on the growth performance and rumen
      fermentation characteristics of veal calves. For this purpose, 160 Holstein
      Friesian x Dutch Friesian crossbred male calves were used in a complete
      randomized block design with a 5 x 2 factorial arrangement. Dietary treatments
      consisted of 1) milk replacer control, 2) pectin-based concentrate, 3) neutral
      detergent fiber-based concentrate, 4) starch-based concentrate, and 5) mixed
      concentrate (equal amounts of concentrates of treatments 2, 3, and 4).
      Concentrate diets were provided as pellets in addition to a commercial milk
      replacer. Calves were euthanized either at the end of 8 or 12 wk of age. The
      overall dry matter intake of the concentrate diets varied between 0.37 and 0.52
      kg/d. Among the concentrate diets, the dry matter intake was lower in the starch
      diet (0.37 kg/d of dry matter) and differed between the NDF and pectin diets. The
      average daily gain for all the dietary treatments varied between 0.70 and 0.78
      kg/d. The mixed- and NDF-fed calves had an increased average daily gain (0.78 and
      0.77 kg/d, respectively) compared with the starch- and pectin-fed calves (0.70
      and 0.71 kg/d, respectively). Rumen fermentation in the calves fed concentrates
      was characterized by a low pH (4.9 to 5.2), volatile fatty acid concentrations
      between 100 and 121 mmol/L, and high concentrations of reducing sugars (33 to 66
      g/kg of dry matter). The volatile fatty acid concentrations of calves fed
      concentrates were higher than those of the control calves. All concentrate
      treatments showed a low acetate-to-propionate ratio in rumen fluid (between 1.3
      and 1.9). Among the concentrates, the NDF diet had the highest (55.5%) and starch
      the lowest (45.5%) molar proportions of acetate. Calves fed the mixed, pectin,
      and starch diets had significantly higher molar proportions of butyrate (13.1 to
      15.8%) than the NDF- and control-fed groups (9.9 and 9.6%, respectively). Calves
      fed the control diet had a higher lactate concentration (21 mmol/L) than the
      concentrate-fed calves (between 5 and 11 mmol/L). With the exception of the NDF
      diet, polysaccharide-degrading enzyme activities in the rumen contents generally
      showed an adaptation of the microorganisms to the carbohydrate source in the
      diet. The mixed diet exhibited the least variation in rumen polysaccharide
      degrading enzyme activities among the enzymes systems tested. Results indicated
      that the carbohydrate source can influence intake, growth rate, and rumen
      fermentation in young veal calves.

PMID- 17033025
TI  - Effects of supplementing concentrates differing in carbohydrate composition in
      veal calf diets: II. Rumen development.
AB  - The objective of this experiment was to examine the effects of concentrates in
      feed, differing in carbohydrate source, on the rumen development of veal calves.
      For this purpose, 160 male Holstein Friesian x Dutch Friesian crossbred calves
      were used in a complete randomized block design with a 5 x 2 factorial
      arrangement. Dietary treatments consisted of 1) a milk replacer control, 2) a
      pectin-based concentrate, 3) a neutral detergent fiber-based concentrate, 4) a
      starch-based concentrate, and 5) a mixed concentrate (equal amounts of the
      concentrates in treatments 2, 3, and 4). Concentrate diets were provided as
      pellets in addition to a commercial milk replacer. Calves were euthanized at
      either 8 or 12 wk of age. Plasma acetate and beta-hydroxybutyrate (BHBA) were
      measured as indicators of rumen development. Empty rumen weight was determined,
      and wall samples were taken at slaughter. In most calves, a poorly developed
      rumen mucosa was observed. Coalescing rumen papillae with embedded hair, feed
      particles, and cell debris were found in all calves fed the concentrate diets.
      Calves fed concentrates had significantly heavier rumens than calves fed the
      control diet. In the dorsal location of the rumen, calves fed concentrate diets
      showed an increased ratio of mucosa to serosa length compared with calves fed the
      control diet, whereas in the ventral location only, calves fed the pectin and
      mixed diets showed larger ratios of mucosa to serosa length. Mucosa thickness and
      muscle thickness were greater in the ventral and dorsal locations of the rumen,
      respectively. In both locations, the NDF diet resulted numerically in the lowest
      mucosa thickness and highest muscle thickness among the concentrate treatments.
      At 8 wk, calves fed the concentrate diets had higher plasma acetate
      concentrations than calves on the control treatment. However, at 12 wk, only NDF
      fed calves showed significantly higher plasma acetate concentrations. The plasma
      BHBA concentrations of calves at 8 wk of age fed the pectin and mixed diets were
      higher than those of the control diet-fed calves. At 12 wk, no differences in
      BHBA concentrations were observed among treatments. Results of a principal
      component analysis indicated that, in addition to rumen volatile fatty acid
      concentrations, other factors were likely to affect rumen development, and that
      the relationships between rumen development and individual types of volatile
      fatty acids present in the rumen liquor were similar. Also, variations in rumen
      development coincided with variations in plasma acetate and BHBA concentrations.

PMID- 17033026
TI  - Effect of different forms of methionine on lactational performance of dairy cows.
AB  - Methionine is one of the first limiting AA in dairy cows. The use of rumen
      protected Met to correct deficient diets is limited by the lack of a product that
      could be incorporated into a pelleted concentrate. The main objective of this
      trial was to test, at practical doses (approximately 10 g of absorbable Met), the
      efficacy of 2 forms of pelletable Met hydroxy analogs, D,L-2-hydroxy-4
      (methylthio)-butanoic acid (HMB) and the isopropyl ester of HMB (HMBi), to
      provide Met to cows, especially for milk protein synthesis, compared with a
      negative control and to Smartamine M (SmM). These treatments were tested
      according to a 4 x 4 Latin square in 16 Holstein cows. Plasma Met concentrations
      were increased by 110 and 65% that of the control value after HMBi and SmM
      treatments, respectively. Milk protein yield increased by 32 and 41 g/d for HMBi
      and SmM, respectively. D,L-2-hydroxy-4-(methylthio)-butanoic acid supplementation
      did not improve Met availability to the cows for milk protein synthesis. The HMBi
      treatment induced an increase in 15:0 in milk at the expense of a general
      reduction in even-numbered short-and medium-chain fatty acids. Moreover, HMBi and
      SmM supplements led to an increase in the saturation level of C18 fatty acids
      consistent with the improvement of Met supply. It was concluded that HMBi is a
      new "rumen-protected" form of Met that can be supplied to cows integrated into
      pellets.

PMID- 17033027
TI  - Slow-release urea and highly fermentable sugars in diets fed to lactating dairy
      cows.
AB  - This experiment was designed to test the inclusion of highly fermentable sugars
      (FS) in dairy rations and their interactions with a slow-release urea (SU)
      product. The FS are a blend of liquid coproducts from the corn milling and cheese
      industries, and the SU is calcium chloride urea. Eight multiparous and 4
      primiparous Brown Swiss cows (117 +/- 46 d in milk) were blocked by parity and
      utilized in a multiple Latin square design. Basal diets were formulated for 16.6%
      crude protein and 1.55 Mcal/kg of net energy for lactation and contained 35% of
      dietary dry matter as corn silage, 15% alfalfa hay, 34% of a concentrate mix
      containing varying proportions of ground shelled corn and soybean meal, and 16%
      of a constant concentrate premix. The premix consisted of equal proportions of
      corn distillers grains, soybean hulls, expeller soybean meal, vitamins, and
      minerals across all diets. Diets contained either no supplemental FS (NFS) or FS
      (8.64% RationMate) and either no SU (NSU) or SU (0.61% Ruma Pro) in a 2 x 2
      factorial arrangement of treatments. Feeding FS tended to decrease milk
      production compared with feeding NFS. Milk fat percentage was increased for cows
      fed FS compared with NFS. Feeding SU decreased dry matter intake and increased
      feed efficiency compared with cows fed NSU. Dietary treatment had no effect on
      energy-corrected milk, milk fat yield, milk protein percentage, or milk urea N.
      Feeding FS increased the molar proportion of ruminal butyrate and decreased the
      molar proportion of propionate; however, no other effects were observed on
      ruminal fermentation. No interactions between FS and SU were observed. It was
      concluded that the replacement of corn and soybean meal with dietary FS increased
      milk fat percentage and that the replacement of soybean meal with SU
      significantly improved feed efficiency.

PMID- 17033028
TI  - Rumen lipopolysaccharide and inflammation during grain adaptation and subacute
      ruminal acidosis in steers.
AB  - Three rumen-fistulated Jersey steers were gradually adapted to a wheat-barley
      concentrate over a 4-wk period. Adaptation steps consisted of four 1-wk periods
      during which steers were fed diets with forage-to-concentrate (F:C) ratios of
      100:0, 79:21, 59:41, and 39:61. The forage consisted of chopped hay (CH), and the
      concentrate consisted of pelleted concentrate containing 50% ground wheat and 50%
      ground barley. Steers were fed the all-forage diet ad libitum during wk 1. Feed
      offered in wk 2 to 4 was kept constant at the ad libitum intake during wk 1. On 2
      d that were set 3 d apart during wk 5, subacute ruminal acidosis (SARA) was
      induced in the steers by feeding a diet with an F:C ratio of 24:76 by offering
      them 0.9 kg of CH at 0900 h followed by 2 meals of 3.0 kg each of wheat-barley
      pellets (WBP) at 1100 h and 1300 h and 0.9 kg of CH at 1700 h, to depress rumen
      pH for at least 3 h/d below 5.6. The average concentrate inclusion for the SARA
      induction diet was 76 +/- 10% DM. During stepwise adaptation, time with pH below
      5.6 increased to an average of 121 min/d when the steers were consuming a diet
      containing 61% DM as WBP. Dietary inclusion of WBP at the rate of 76% DM induced
      SARA because the steers spent an average of 219 min/d with pH below 5.6. The free
      ruminal lipopolysaccharide (LPS) concentration increased from 6,310 endotoxin
      units (EU)/mL with the all-forage diet to 18,197 EU/mL with the 61% concentrate
      diet. The ruminal LPS concentration increased to 26,915 EU/mL when SARA was
      induced. Serum haptoglobin increased from 0.53 mg/mL when steers were on the all
      forage diet to 1.90 mg/mL with the 61% concentrate diet and were not increased
      further by inducing SARA. The serum amyloid-A concentration was not affected by
      increasing dietary concentrate during stepwise adaptation to the concentrate, but
      increased from 71 to 163 microg/mL when SARA was induced. A gradual increase in
      dietary concentrate so that the F:C ratio decreased to 39:61 resulted in
      increased ruminal LPS concentrations. Subsequent induction of SARA further
      increased ruminal LPS and activated an inflammatory response.

PMID- 17033029
TI  - Aberrant low expression level of bovine beta-lactoglobulin is associated with a C
      to A transversion in the BLG promoter region.
AB  - Beta-lactoglobulin (beta-LG) is the major whey protein in cow's milk. It is well
      established that the predominant 2 genetic variants, beta-LG A and B, are
      differentially expressed. Extensive investigation of the genetic variation in the
      promoter region of the BLG gene revealed the existence of specific haplotypes
      associated with the A and B variants, respectively. However, the genetic basis
      for the differential expression of BLG A and B alleles is still elusive. We have
      previously reported a quantitative beta-LG B variant, characterized by a very low
      beta-LG protein expression level. Here, we report that the corresponding BLG
      allele (BLG B*) shows a correspondingly low mRNA expression level. Comparative
      DNA sequencing of 7,670 bp of the BLG B* allele and the established BLG B allele
      revealed a unique difference of a C to A transversion at position 215 bp upstream
      of the translation initiation site (g.-215C>A). This mutation segregated
      perfectly with the differential phenotypic expression in a paternal half-sib
      family and could be confirmed in 2 independent cases. The sequence of the BLG B
      allele in the region of the mutation is highly conserved among 4 related ruminant
      species. The site of the mutation corresponds to a putative consensus-binding
      sequence for the transcription factors c-Rel and Elk-1 as predicted by searching
      the TRANSFAC database. The beta-LG B* site might be relevant in the natural
      production of milk of low beta-LG content.

PMID- 17033030
TI  - Short communication: Genetic analysis of nonreturn rate and mastitis in first
      lactation Norwegian Red cows.
AB  - Associations between clinical mastitis (CM) and nonreturn rate within 56 d after
      first insemination (NR56) were examined in Norwegian Red (NRF) cows. Records on
      absence or presence of CM within each of the intervals, -30 to 30, 31 to 150, and
      151 to 300 d after first calving, and records on NR56 for 620,492 first-lactation
      daughters of 3,064 NRF sires were analyzed with a Bayesian multivariate threshold
      liability model. Point estimates of genetic correlations between NR56 and the 3
      CM traits were between -0.05 and -0.02. Residual correlations were close to zero,
      and correlations between herd-5-yr effects on NR56 and CM in the 3 lactation
      intervals ranged from -0.15 to -0.17. It appears that CM and NR56 in first
      lactation are independent traits.

PMID- 17033031
TI  - Genetics of body condition score in New Zealand dairy cows.
AB  - Body condition score (BCS) data were collected on 169,661 first-parity cows from
      herds participating in progeny testing schemes and linear type assessment.
      Genetic and residual variances for BCS estimated across time using a quadratic
      random regression model were found to be largest at the start of lactation.
      Heritability estimates ranged from 0.32 to 0.23 from d 1 to 200 of lactation,
      with a mean of 0.26. Genetic correlations between BCS and other traits were
      estimated using 2 approaches: 1) a multivariate analysis that included BCS and
      live weight, both adjusted for stage of lactation; 270-d cumulative yields of
      milk, fat, and protein; average somatic cell score; and 2 measures of fertility;
      and 2) a bivariate random regression analysis in which BCS was considered to be a
      longitudinal trait across time, with the same measurements as in approach 1 for
      all other traits. Genetic correlations of BCS with the 2 fertility traits were
      0.43 and 0.50 using the multivariate analysis; the corresponding random
      regression estimates between BCS as a longitudinal trait across time and 2
      measures of fertility were 0.35 to 0.44 and 0.40 to 0.49, and tended to increase
      with stage of lactation. Genetic correlations estimated using the random
      regression model fluctuated around the multivariate estimates for live weight and
      somatic cell score, which were 0.50 and -0.12, respectively. Genetic correlations
      estimated using the multivariate analysis of BCS with fat and protein yields were
      close to zero. With the random regression model, genetic correlations between BCS
      and fat and protein yields were positive at d 1 of lactation (0.16 and 0.08,
      respectively) and were negative by d 200 of lactation (-0.25 and -0.20,
      respectively). In pastoral production systems, such as those typical in New
      Zealand, there appears to be an advantage in the total lactation yields of fat
      and protein for cows of higher BCS in early lactation, which is likely to be
      because these cows have body reserves that are available to be mobilized in later
      lactation, when feed resources are sometimes limited.

PMID- 17033032
TI  - Effects of the signal transducer and activator of transcription 1 (STAT1) gene on
      milk production traits in Holstein dairy cattle.
AB  - A functional candidate gene approach was used to search for genes affecting milk
      production traits in Holstein dairy cattle. Signal transducer and activator of
      transcription 1 (STAT1) was chosen because of its involvement in the development
      of the mammary gland. Using the pooled genomic DNA sequencing approach, we
      identified a single nucleotide polymorphism. Genomic DNA was extracted from 1,292
      sons obtained from the Cooperative Dairy DNA Repository and from 715 blood
      samples of daughters of 12 bulls obtained from the University of Wisconsin
      resource population. Daughter yield deviation data for the sons and yield
      deviation for the daughters were obtained for milk production traits from the
      USDA Animal Improvement Programs Laboratory. For the Repository population,
      allele C was associated with significant increases in milk fat and protein
      percentages. For the University of Wisconsin population, genotypes CC and CT were
      associated with significant increases in milk, fat, and protein yields. Results
      from this study are consistent with previous studies on the role of STAT1 in
      regulating the transcription of genes involved in milk protein synthesis and fat
      metabolism.

PMID- 17033033
TI  - Selection for female fertility using censored fertility traits and investigation
      of the relationship with milk production.
AB  - Bivariate models (censored linear-linear and censored threshold-linear) were used
      to estimate genetic parameters for production and fertility traits in the Spanish
      Holstein population. Records on 71,217 lactations from 41,515 cows were used: 30
      and 36% of lactations were censored for days open (DO) and number of
      inseminations to conception (INS), respectively. Heritability estimates for
      production traits (milk, fat, protein) ranged between 0.18 and 0.25. Heritability
      of days to first service (DFS) and DO was 0.05; heritability of INS on the
      liability scale was 0.04. Genetic correlations between fertility traits were
      0.41, 0.71, and 0.87 for DFS-INS, DO-INS, and DO-DFS, respectively. Days open had
      a larger genetic correlation (ranging from 0.63 to 0.76) with production traits
      than did DFS (0.47 to 0.59) or INS (0.16 to 0.23). Greater antagonism between
      production and DO may be due to voluntary management decisions for high-yielding
      cows, resulting in longer lactation lengths. Inseminations to conception appeared
      to be less correlated with milk production than were the other 2 female fertility
      traits. Including INS in a total merit index would be expected to increase
      genetic gain in terms of profit, but profit would decrease if either DO or DO and
      DFS were included in the index. Thus, INS is the trait to be preferred when
      selecting for female fertility. The genetic correlation between actual milk yield
      and 305-d standardized milk yield was 0.96 in the present study, suggesting that
      some reranking of sires could occur. Because the target of attaining a 12-mo
      calving interval, as implied by a 305-d standardized lactation length, is
      changing in the dairy industry, routine genetic evaluation of actual total
      lactation milk yield should be considered.

PMID- 17033034
TI  - A structural equation model for describing relationships between somatic cell
      score and milk yield in first-lactation dairy cows.
AB  - Relationships between production and diseases may involve recursive or
      simultaneous effects between traits. Four structural equation models (SEqM) for
      somatic cell score and milk yield, with varying specifications for the effects
      relating the 2 traits, were compared. Data consisted of repeated records of milk
      yield and somatic cell score of 33,453 first-lactation daughters of 245 Norwegian
      Red sires that had their first progeny test in 1991 and 1992. All models included
      random effects of the sire and of the cow and were fitted using the LISREL
      software. The Bayesian information criterion clearly favored a model with a
      recursive effect from somatic cell score on milk yield over the 3 other models
      fitted (absence of recursive effects; an effect from milk yield on somatic cell
      score; simultaneity of effects between the 2 traits). This provides evidence that
      the negative association between milk yield and somatic cell score is more likely
      due to an effect of infection (measured indirectly by the somatic cell score) on
      production than to a dilution effect. Estimates indicated that a mastitis event
      would reduce milk yield in the following 15 d by about 900 g/d. The estimated
      genetic (co)variances did not change sizably when the specification of recursive
      or simultaneous effects was varied. However, estimates of the phenotypic
      covariance were altered when a recursive effect from somatic cell score on milk
      yield was included in the model.

PMID- 17033035
TI  - Detection and characterization of Listeria monocytogenes in Sao Jorge (Portugal)
      cheese production.
AB  - Listeria monocytogenes is a foodborne pathogen that can cause serious invasive
      disease in humans. Because human listeriosis cases have previously been linked to
      consumption of contaminated cheese, control of this pathogen throughout the
      cheese production chain is of particular concern. To understand the potential for
      L. monocytogenes transmission via Sao Jorge cheese, a Portuguese artisanal cheese
      variety that bears a Protected Denomination of Origin classification, 357 raw
      milk, curd, natural whey starter, and cheese samples representative of the
      production chain of this cheese were collected over one year and tested for the
      presence of L. monocytogenes and selected physicochemical parameters. Although
      neither L. monocytogenes nor other Listeria spp. were detected in whey, curd, or
      cheese samples, 2 of the 105 raw milk samples analyzed were positive for L.
      monocytogenes. These 2 raw milk isolates represented a ribotype that has
      previously been linked to multiple human listeriosis outbreaks and cases
      elsewhere, indicating the potential of these isolates to cause human listeriosis.
      On average, physicochemical parameters of Sao Jorge cheese ripened for 4 mo
      presented values that likely minimize the risk of L. monocytogenes outgrowth
      during ripening and storage (mean pH = 5.48; mean moisture = 37.79%; mean NaCl
      concentration = 4.73%). However, some cheese samples evaluated in this study were
      characterized by physicochemical parameters that may allow growth and survival of
      L. monocytogenes. Even though our results indicate that raw milk used for Sao
      Jorge cheese manufacture as well as finished products is rarely contaminated with
      L. monocytogenes, continued efforts to control the presence of this pathogen in
      the Sao Jorge cheese production chain are urged and are critical to ensure the
      safety of this product.

PMID- 17033036
TI  - Stochastic models for simulating parallel, rotary, and side-opening milking
      parlors.
AB  - Simulation models of parallel, rotary, and side-opening milking parlors were
      built that could predict milking parlor performance according to herd size,
      number of milking stalls, labor quality, and cow characteristics. The models were
      validated by statistically comparing the duration of the simulated milking
      process with actual data collected at 3 dairy farms during 12 mo. Various
      scenarios were generated to study parlor performance, and the results indicated
      that for a parlor with up to 14 milking stalls, a side-opening design provided
      greater capacity than parallel or rotary parlors. Performance of a side-opening
      parlor was reduced by enlargement up to 20 milking stalls. For 10 to 40 milking
      stalls, a rotary design gave better performance than a double parallel design in
      terms of milking process duration and stall utilization. The presented models can
      serve as a practical tool in designing new parlors or changing operations of
      existing ones.

PMID- 17033037
TI  - American Society of Clinical Oncology 2006 update of the breast cancer follow-up
      and management guidelines in the adjuvant setting.
AB  - PURPOSE: To update the 1999 American Society of Clinical Oncology (ASCO)
      guideline on breast cancer follow-up and management in the adjuvant setting.
      METHODS: An ASCO Expert Panel reviewed pertinent information from the literature
      through March 2006. More weight was given to studies that tested a hypothesis
      directly relating testing to one of the primary outcomes in a randomized design.
      RESULTS: The evidence supports regular history, physical examination, and
      mammography as the cornerstone of appropriate breast cancer follow-up. All
      patients should have a careful history and physical examination performed by a
      physician experienced in the surveillance of cancer patients and in breast
      examination. Examinations should be performed every 3 to 6 months for the first 3
      years, every 6 to 12 months for years 4 and 5, and annually thereafter. For those
      who have undergone breast-conserving surgery, a post-treatment mammogram should
      be obtained 1 year after the initial mammogram and at least 6 months after
      completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly
      mammographic evaluation should be performed. Patients at high risk for familial
      breast cancer syndromes should be referred for genetic counseling. The use of
      CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasounds,
      computed tomography scans, [18F]fluorodeoxyglucose-positron emission tomography
      scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen,
      CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in
      an otherwise asymptomatic patient with no specific findings on clinical
      examination. CONCLUSION: Careful history taking, physical examination, and
      regular mammography are recommended for appropriate detection of breast cancer
      recurrence.

PMID- 17033038
TI  - Number of CD4+ cells and location of forkhead box protein P3-positive cells in
      diagnostic follicular lymphoma tissue microarrays correlates with outcome.
AB  - PURPOSE: To examine the immune microenvironment in diagnostic follicular lymphoma
      (FL) biopsies and evaluate its prognostic significance. PATIENTS AND METHODS:
      Immunohistochemistry was used to study numbers and location of cells staining
      positive for immune cell markers CD4, CD7, CD8, CD25, CD68, forkhead box protein
      P3 (FOXP3), T-cell intracellular antigen-1, and Granzyme B in tissue microarrays
      of paraffin-embedded, diagnostic lymph node biopsies taken from 59 FL patients
      who lived less than 5 years (short-survival group; n = 34) and more than 15 years
      (long-survival group; n = 25). RESULTS: CD4 and FOXP3 expression were
      significantly different between the two groups. Samples from the long-survival
      group were more likely than those from the short-survival group to have CD4+
      staining cells and to have FOXP3-positive cells in a perifollicular location.
      CONCLUSION: This study has identified differences in immune cell composition of
      the diagnostic FL lymph node immune microenvironment and these have the potential
      for use as prognostic biomarkers in a routine histopathology setting.

PMID- 17033039
TI  - Phase III trial comparing three doses of docetaxel for second-line treatment of
      advanced breast cancer.
AB  - PURPOSE: To evaluate whether a relationship exists between docetaxel dose and
      clinical response in the treatment of patients with advanced breast cancer.
      PATIENTS AND METHODS: Patients whose cancer had progressed after one prior
      chemotherapy regimen for advanced breast cancer or had recurred during or within
      6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or
      100 mg/m2 intravenously every 3 weeks. RESULTS: Five hundred twenty-seven
      patients were randomly assigned (intent to treat [ITT]), and 524 were assessable
      for toxicity. In the population assessable for efficacy (n = 407), logistic
      regression analysis showed that increasing docetaxel dose was significantly
      associated with higher response rate (P = .007) and improved time to progression
      (TTP; P = .014). In the ITT analysis, a significant dose-response relationship
      was observed for tumor response (P = .026) but not for TTP (P = .067). The
      incidences of most hematologic and nonhematologic toxicities were related to
      increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and
      93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients
      administered the 60, 75, and 100 mg/m2 doses, respectively. One death was
      considered treatment related. CONCLUSION: A relationship between increasing dose
      of docetaxel and increased tumor response was observed across the dose range of
      60 to 100 mg/m2 every 3 weeks. Toxicities were related to increasing dose.
      Depending on the therapy goal, any of the doses studied may be appropriate for
      second-line treatment of advanced breast cancer.

PMID- 17033040
TI  - A new evaluation method for lumbar spinal instability: passive lumbar extension
      test.
AB  - BACKGROUND AND PURPOSE: Although many studies have described clinical examination
      measures for the diagnosis of lumbar spinal instability, few of them have
      investigated the sensitivity and specificity of the measures that were used. The
      authors devised a passive lumbar extension (PLE) test for assessing lumbar spinal
      instability. The purpose of this study was to investigate the sensitivity,
      specificity, and positive likelihood ratio of this test. SUBJECTS AND METHODS:
      The PLE test as well as the instability catch sign, painful catch sign, and
      apprehension sign tests were done for 122 subjects with lumbar degenerative
      diseases. The subjects were divided into 2 groups-instability positive and
      instability negative-on the basis of findings on flexion-extension films of the
      lumbar spine. The sensitivity, specificity, predictive values, and positive
      likelihood ratio of each test were investigated. RESULTS: The sensitivity and
      specificity of the PLE test were 84.2% and 90.4%, respectively. These values were
      higher than those of other signs. The positive likelihood ratio of the PLE test
      was 8.84 (95% confidence interval=4.51-17.33). DISCUSSION AND CONCLUSION: The PLE
      test is an effective method for examining patients for lumbar spinal instability
      and can be performed easily in an outpatient clinic.

PMID- 17033041
TI  - Lengthening the hamstring muscles without stretching using "awareness through
      movement".
AB  - BACKGROUND AND PURPOSE: Passive stretching is widely used to increase muscle
      flexibility, but it has been shown that this process does not produce long-term
      changes in the viscoelastic properties of muscle as originally thought. The
      authors tested a method of lengthening hamstring muscles called "Awareness
      Through Movement" (ATM) that does not use passive stretching. SUBJECTS: Thirty
      three subjects who were randomly assigned to ATM and control groups met the
      screening criteria and completed the intervention phase of the study. METHODS:
      The ATM group went through a process of learning complex active movements
      designed to increase length in the hamstring muscles. Hamstring muscle length was
      measured before and after intervention using the Active Knee Extension Test.
      RESULTS: The ATM group gained significantly more hamstring muscle length (+7.04
      degrees ) compared with the control group (+1.15 degrees ). DISCUSSION AND
      CONCLUSION: The results suggest that muscle length can be increased through a
      process of active movement that does not involve stretching. Further research is
      needed to investigate this finding.

PMID- 17033043
TI  - D-serine regulation of NMDA receptor activity.
AB  - The N-Methyl-D-aspartate-type glutamate receptor (NMDAR) plays a key role in
      several important processes involving the nervous system, including brain
      development, synaptic plasticity, and learning. Unlike other neurotransmitter
      receptors, which are activated by individual neurotransmitters, activation of
      NMDARs requires the binding of a coagonist (D-serine or glycine) in addition to
      glutamate. Although previously considered an "unnatural" amino acid, D-serine is
      a key regulator of NMDAR activity and may be the main physiological ligand at the
      coagonist site. D-Serine is synthesized in the mammalian brain and is enriched in
      astrocytes, a class of glial cells that ensheath synapses in the brain.
      Astrocytes physiologically affect NMDAR neurotransmission by releasing D-serine,
      suggesting that D-serine acts as a gliotransmitter. However, recent findings
      indicate that D-serine signaling does not depend solely on glia, because D-serine
      and its biosynthetic enzyme are also present in substantial amounts in neurons.
      Here, we discuss these new findings, which begin to shed light on the relative
      roles of glia and neurons in D-serine signaling.

PMID- 17033044
TI  - A unified model of the presynaptic and postsynaptic changes during LTP at CA1
      synapses.
AB  - Long-term potentiation (LTP) has been studied extensively at CA1 synapses of the
      hippocampus, and there is evidence implicating both postsynaptic and presynaptic
      changes in this process. These changes include (i) addition of AMPA channels to
      the extrasynaptic membrane and diffusional equilibrium of extrasynaptic receptors
      with synaptic receptors, (ii) sudden addition of AMPA channels to the synapse in
      large groups, (iii) a change in the mode of glutamate release (presumably from
      kiss-and-run to full fusion), and (iv) a delayed increase in the number of
      vesicles released. However, it remains unclear whether (or how) these changes
      work together. We have incorporated all of these processes into a structural
      model of the synapse. We propose that the synapse is composed of transsynaptic
      modules that function quasi-independently in AMPA-mediated transmission. Under
      basal conditions, synapses are partially silent; some modules are AMPA-silent
      (but contribute to NMDA-mediated transmission), whereas others are functional
      (and contribute to both AMPA- and NMDA-mediated transmission). During LTP, there
      is both a rapid change in the mode of vesicle fusion and a rapid insertion of a
      postsynaptic complex (a hyperslot) containing many proteins (slots) capable of
      binding AMPA channels. The combined effect of these pre- and postsynaptic changes
      is to convert AMPA-silent modules into functional modules. Slot filling is
      transiently enhanced by a rapid increase in extrasynaptic GluR1, a form of the
      AMPA-type receptor. A slower transsynaptic growth process adds AMPA-silent
      modules to the synapse, enhancing the number of vesicles released and thereby
      enhancing the NMDA response. This model accounts for a broad range of data,
      including the LTP-induced changes in quantal parameters. The model also provides
      a coherent explanation for the diverse effects of GluR1 knockout on basal
      transmission, LTP, and distance-dependent scaling.

PMID- 17033045
TI  - Molecular signaling mechanisms underlying epileptogenesis.
AB  - Epilepsy, a disorder of recurrent seizures, is a common and frequently
      devastating neurological condition. Available therapy is only symptomatic and
      often ineffective. Understanding epileptogenesis, the process by which a normal
      brain becomes epileptic, may help identify molecular targets for drugs that could
      prevent epilepsy. A number of acquired and genetic causes of this disorder have
      been identified, and various in vivo and in vitro models of epileptogenesis have
      been established. Here, we review current insights into the molecular signaling
      mechanisms underlying epileptogenesis, focusing on limbic epileptogenesis. Study
      of different models reveals that activation of various receptors on the surface
      of neurons can promote epileptogenesis; these receptors include ionotropic and
      metabotropic glutamate receptors as well as the TrkB neurotrophin receptor. These
      receptors are all found in the membrane of a discrete signaling domain within a
      particular type of cortical neuron--the dendritic spine of principal neurons.
      Activation of any of these receptors results in an increase Ca2+ concentration
      within the spine. Various Ca2+-regulated enzymes found in spines have been
      implicated in epileptogenesis; these include the nonreceptor protein tyrosine
      kinases Src and Fyn and a serine-threonine kinase [Ca2+-calmodulin-dependent
      protein kinase II (CaMKII)] and phosphatase (calcineurin). Cross-talk between
      astrocytes and neurons promotes increased dendritic Ca2+ and synchronous firing
      of neurons, a hallmark of epileptiform activity. The hypothesis is proposed that
      limbic epilepsy is a maladaptive consequence of homeostatic responses to
      increases of Ca2+ concentration within dendritic spines induced by abnormal
      neuronal activity.

PMID- 17033046
TI  - Carrot (Daucus carota L.).
AB  - Plants are susceptible to infection by a broad range of fungal pathogens. Many
      horticulturally important crop species lack adequate genetic resistance to
      disease. Studies on potential mechanisms of disease resistance in plants have
      revealed the importance of a range of pathogenesis-related (PR) proteins with
      antifungal activity in reducing colonization of plant tissues by pathogens. We
      are evaluating a range of PR-proteins, through heterologous expression in
      transgenic carrot tissues, for their effects on fungal disease development. The
      protocols for carrot transformation with a thaumatin-like protein are described.
      In addition, the use of herbicide resistance as a selectable marker in carrot
      transformation is illustrated. In this protocol, petiole segments from carrot
      seedlings are exposed to Agrobacterium for 10-30 min and co-cultivated for 3 d,
      after which herbicide selection is imposed until embryogenic calli are produced
      after 8-12 wk. The transfer of the embryogenic calli to hormone-free medium
      yields transgenic plantlets. This genetic transformation protocol has supported
      the generation of transgenic carrot plants with defined T-DNA inserts at the rate
      of between 1 and 3 Southern positive independent events out of 100.

PMID- 17033048
TI  - Potato (Solanum tuberosum L.).
AB  - Potato (Solanum tuberosum L.) is a globally important crop plant producing high
      yields of nutritionally valuable food in the form of tubers. It has been the
      focus of substantial study because of its use both as a staple food crop and as a
      potentially significant source of compounds of interest. This has included the
      development and application of transgenic technology for introducing novel traits
      of fundamental and applied interest. This chapter describes a rapid, efficient,
      and cost-effective system for the routine transformation of this crop plant at
      rates above 40% efficiency, calculated as the mean number of Southern blot-
      confirmed independent transgenics per number of internodal explants originally
      plated. Internodal sections are co-cultivated with Agrobacterium tumefaciens and
      subjected to a two-stage callus induction/shoot outgrowth system under kanamycin
      selection. Shoot regeneration rates are high using the described method, and
      excised independent shoots rooting from the cut end of the stem after two further
      subcultures on kanamycin are 95% certain to be transformed. The transgenic status
      can be confirmed by molecular analysis and the plants grown on for tuber
      production enabling a wide spectrum of further studies.

PMID- 17033047
TI  - Cassava (Manihot esculenta Crantz).
AB  - During the last three years the generation of stably transformed cassava plants
      having value-added traits has become a reality. Currently, two Agrobacterium
      mediated transformation systems are routinely used to engineer cassava. These
      systems use either somatic embryos or friable embryogenic calli. This paper
      presents detailed protocols for the transformation of cassava using primary
      somatic embryos. The effects of explant types, tissue culture conditions, and
      bacterial and plasmid related factors on transformation efficiency are discussed.

PMID- 17033049
TI  - Sweet Potato [Ipomoea batatas (L.) Lam].
AB  - Among the available transformation methods reported on sweet potato,
      Agrobacterium tumefaciens-mediated transformation is more successful and
      desirable. Stem explants have shown to be ideal for the transformation of sweet
      potato because of their ready availability as explants, the simple transformation
      process, and high-frequency-regeneration via somatic embryogenesis. Under the two
      step kanamycin-hygromycin selection method and using the appropriate explants
      type (stem explants), the efficiency of transformation can be considerably
      improved in cv. Beniazuma. The high efficiency in the transformation of stem
      explants suggests that the transformation protocol described in this chapter
      warrants testing for routine stable transformation of diverse varieties of sweet
      potato.

PMID- 17033050
TI  - Bermudagrass (Cynodon spp.).
AB  - Bermudagrass is an important warm-season forage and turf species widely grown in
      the southern United States. This chapter describes a rapid and efficient protocol
      that allows for the generation of a large number of transgenic bermudagrass
      plants, bypassing the callus formation phase. Stolon nodes are infected and co
      cultivated with Agrobacterium tumefaciens harboring pCAMBIA binary vectors.
      Hygromycin phosphotransferase gene (hph) is used as the selectable marker and
      hygromycin is used as the selection agent. Green shoots are directly produced
      from infected stolon nodes 4 to 5 wk after hygromycin selection. Without callus
      formation and with minimum tissue culture, this procedure allowed us to obtain
      well-rooted transgenic plantlets in only 7 wk and greenhouse-grown plants in only
      9 wk.

PMID- 17033051
TI  - Perennial Ryegrass (Lolium perenne L.).
AB  - A protocol that facilitates rapid establishment of Agrobacterium-mediated
      transformation for perennial ryegrass is described. The synthetic green
      fluorescent protein (sgfpS65T) reporter gene is introduced in combination with
      the nptII selectable marker gene into axillary bud derived embryogenic calli of
      perennial ryegrass (Lolium perenne L.) by co-cultivation with Agrobacterium
      tumefaciens strain AGL0 harboring binary vector pYF132. Following the co
      cultivation calli are cultured for 48 h in liquid callus medium containing
      timentin at 10 degrees C and 70 rpm, which reduces Agrobacterium overgrowth.
      Using green fluorescent protein (GFP) as a nondestructive visual marker allows
      identification of responsive genotypes and transgenic cell clusters at an early
      stage. GFP screening is combined with paromomycin selection to suppress wild type
      cells. Transgenic plantlets ready to transfer to soil are obtained within 4 mo of
      explant culture. Between 8 and 16% of the Agrobacterium-inoculated calli
      regenerate independent, Southern positive transgenic plants. Reproducibility and
      efficiency in this perennial ryegrass transformation protocols is controlled by
      multiple factors including genotype dependent tissue culture and gene transfer
      response, a short tissue culture-and-selection period and the efficient
      suppression of Agrobacterium following Agrobacterium-mediated gene transfer.

PMID- 17033052
TI  - Switchgrass (Panicum virgatum L.).
AB  - During the last decade, Agrobacterium-mediated transformation of more than a
      dozen monocotyledonous plants, including forage and turf grasses, has been
      achieved. So far, switchgrass is the only warm season grass that has been
      transformed with A. tumefaciens. We have developed a highly efficient system for
      transformation of different switchgrass explants utilizing the A. tumefaciens
      strain AGL1 carrying the binary vector pDM805, containing the phosphinotricin
      acetyltransferase (bar) and beta-glucoronidase (GUS) (uidA or gus) genes.
      Transformed cultures were selected in the presence of 10 mg/L bialaphos and the
      resultant plantlets were treated with the herbicide Basta. The T-DNA delivery
      frequency was affected by the genotype, explant used, and the presence or absence
      of acetosyringone during inoculation and cocultivation. The total time required
      from inoculation to the establishment of plants in soil was 3-4 mo. Stable
      integration, expression, and inheritance of both transgenes were confirmed by
      molecular and genetic analyses. Approximately 90% of the tested plants appeared
      to have only one or two copies of the T-DNA inserts. The transgenes were sexually
      transmitted through both male and female gametes to the progeny obtained from
      controlled crosses in the expected segregation ratio of 1:1 according to a chi(2)
      test at p = 0.05.

PMID- 17033053
TI  - Tall Fescue (Festuca arundinacea Schreb.).
AB  - Tall fescue (Festuca arundinacea Schreb.) is the predominant cool-season
      perennial grass in the United States. It is widely used for both forage and turf
      purposes. This chapter describes a protocol that allows for the generation of
      large number of transgenic tall fescue plants by Agrobacterium-mediated
      transformation. Embryogenic calli induced from caryopsis are used as explants for
      inoculation with A. tumefaciens. The Agrobacterium strain used is EHA105.
      Hygromycin phosphotransferase gene (hph) is used as the selectable marker and
      hygromycin is used as the selection agent. Calli resistant to hygromycin are
      obtained after 4-6 wk of selection. Soil-grown tall fescue plants can be
      regenerated 4-5 mo after Agrobacterium-mediated transformation.

PMID- 17033054
TI  - Turf Grasses.
AB  - A reliable and efficient genetic transformation protocol for various turfgrass
      species and elite cultivars has been achieved using Agrobacterium tumefaciens. We
      describe a general protocol for the establishment of embryogenic cell cultures,
      Agrobacterium tumefaciens-mediated transformation, selection, and regeneration of
      transgenic turfgrass plants. Embryogenic callus is initiated from mature seeds,
      maintained by visual selection, and infected with an Agrobacterium tumefaciens
      strain (LBA4404) that contains either an herbicide-resistant bar gene or an
      antibiotic-resistant hyg gene driven either by a rice ubiquitin or CaMV35S
      promoter. Stable transformation efficiencies up to 43.3% were achieved. Southern
      blot and genetic analysis was used to confirm transgene integration in the
      turfgrass genomes and normal transmission and stable expression of the transgene
      in the T1 generation. We demonstrate herein that five elite cultivars of
      bentgrass can be genetically transformed using this single tissue culture media
      regime. Additionally, we report the successful Agrobacterium-mediated
      transformation of an elite tall fescue variety using minor variations in the same
      transformation protocol.

PMID- 17033055
TI  - American Elm (Ulmus americana).
AB  - American elm (Ulmus americana) is a valuable and sentimental tree species that
      was decimated by Dutch elm disease in the mid-20th century. Therefore, any
      methods for modifying American elm or enhancing disease resistance are
      significant. This protocol describes transformation and tissue culture techniques
      used on American elm. Leaf pieces containing the midvein and petiole are used for
      explants. Agrobacterium tumefaciens strain EHA105 is used for transformation,
      with the binary vector pSE39, containing CaMV35S/nptII as a selectable marker,
      ACS2/ESF39A as a putative resistance enhancing gene, and CaMV35S/GUS as a
      reporter.

PMID- 17033056
TI  - Cork Oak Trees (Quercus suber L.).
AB  - A transformation system for selected mature Quercus suber L. trees using
      Agrobacterium tumefaciens has been established. Embryos obtained from recurrent
      proliferating embryogenic masses are inoculated with AGL1 strain harbouring the
      plasmid pBINUbiGUSint, which carries the nptII and uidA genes. Evidence of stable
      transgene integration is obtained by polymerase chain reaction for nptII and uidA
      genes, Southern blotting and expression of the uidA gene. The transgenic embryos
      are germinated and successfully transferred to soil.

PMID- 17033057
TI  - Eucalyptus.
AB  - Using Eucalyptus camaldulensis as a model system, we describe here a basic
      Agrobacterium-mediated genetic transformation protocol through organogenesis for
      the production of transgenic plants. Hypocotyl segments or cotyledon pieces from
      in vitro seedlings are used as starting materials. The explants are inoculated
      and cocultivated with a disarmed, binary strain of A. tumefaciens CIB542
      harboring a mini Ti plasmid, pBI121. A modified Gamborg's B5 medium is used as
      the basal culture medium throughout stages of co-cultivation, callus induction
      and shoot regeneration. The incorporation of neomycin phosphotransferase II
      (nptII) and beta-glucuronidase (gus) genes into the plant nuclear genome are
      primarily verified by histochemical analysis and polymerase chain reaction (PCR).
      Modifications of this protocol to use in mature tissues derived from elite trees
      and other Eucalyptus species are also described.

PMID- 17033058
TI  - Pine (Pinus radiata).
AB  - This chapter describes the transformation of Pinus radiata using organogenic
      cotyledon explants rather than the more common somatic embryogenesis methods for
      conifers. The advantages of our method are the year round availability of seed
      and that over 80% of genotypes can be easily regenerated from the mature
      cotyledon explants. The transformation efficiency (i.e., the number of
      transformed shoots regenerated from excised cotyledons) is 1.7% and, as with
      other Agrobacterium tumefaciens transformation methods, the majority of transgene
      integrations are single copy. Critical factors for success are survival of the
      cotyledons, Agrobacterium strain, and selection pressure after cocultivation.

PMID- 17033059
TI  - Poplar (Populus spp.).
AB  - Although species within the genus Populus are, in general, easier to transform
      and regenerate in vitro than most other trees, many poplar species are very
      recalcitrant. Many protocols that previously have been reported were developed
      for a specific genotype or species. Thus, it has often been necessary to re
      optimize a protocol each time research is initiated with a new genotype. The
      method presented in this chapter has been effective for a wide variety of poplar
      genotypes.

PMID- 17033061
TI  - Banana (Musa sp.).
AB  - Cultivated bananas are vegetatively propagating herbs, which are difficult to
      breed because of widespread male and female sterility. As a complementary gene
      transfer method in banana, the described Agrobacterium protocol relies on highly
      regenerable embryogenic cell cultures. Embryogenic cells are infected and co
      cultivated in the presence of acetosyringone with Agrobacterium tumefaciens
      harboring a binary plasmid vector to obtain a mixed population of transformed and
      untransformed plant cells. Transformed plant cells are promoted to grow for 2 to
      3 mo on a cell colony induction medium containing the antibiotics geneticin or
      hygromycin as selective agents, while agrobacteria are counterselected by
      timentin. The whole procedure, including plant regeneration, takes approx 6 mo
      and results in an average frequency of 25 to 50 independent transgenic plants per
      plate, which equals 50 mg of embryogenic cells. This method has been applied to a
      wide range of cultivars and to generate large populations of transgenic colonies
      and plants for tagging genes and promoters in banana.

PMID- 17033060
TI  - Rubber Tree (Hevea brasiliensis Muell. Arg).
AB  - Rubber tree (Hevea brasiliensis Muell. Arg.) is an important industrial crop for
      natural rubber production. At present, more than 9.5 million hectares in about 40
      countries are devoted to rubber tree cultivation with a production about 6.5
      million tons of dry rubber each year. The world supply of natural rubber is
      barely keeping up with a global demand for 12 million tons of natural rubber in
      2020. Tapping panel dryness (TPD) is a complex physiological syndrome widely
      found in rubber tree plantations, which causes severe yield and crop losses in
      natural rubber producing countries. Currently, there is no effective prevention
      or treatment for this serious malady. As it is a perennial tree crop, the
      integration of specific desired traits through conventional breeding is both time
      consuming and labour-intensive. Genetic transformation with conventional breeding
      is certainly a more promising tool for incorporation of agronomically important
      genes that could improve existing Hevea genotype. This chapter provides an
      Agrobacterium-mediated transformation protocol for rubber tree using immature
      anther-derived calli as initial explants. We have applied this protocol to
      generate genetically engineered plants from a high yielding Indian clone RRII 105
      of Hevea brasiliensis (Hb). Calli were co-cultured with Agrobacterium tumefaciens
      harboring a plasmid vector containing the Hb superoxide dismutase (SOD) gene and
      the reporter gene used was beta-glucuronidase (GUS) gene (uidA). The selectable
      marker gene used was neomycin phosphotransferase (nptII) and kanamycin was used
      as selection agent. We found that a suitable transformation protocol for Hevea
      consists of a 3-d co-cultivation with Agrobacterium in the presence of 20 mM
      acetosyringone, 15 mM betaine HCl, and 11.55 mM proline followed by selection on
      medium containing 300 mg/L kanamycin. Transformed calli surviving on medium
      containing 300 mg/L kanamycin showed a strong GUS-positive reaction. Upon
      subsequent subculture into fresh media, we obtained somatic embryogenesis and
      germinated plantlets, which were found to be GUS positive. The integration of
      uidA, nptII, and HbSOD transgenes into Hevea genome was confirmed by polymerase
      chain reaction (PCR) as well as Southern blot analysis.

PMID- 17033062
TI  - Citrus.
AB  - Since the initial reports on production of transgenic Citrus via Agrobacterium
      mediated transformation, significant progress has been made, and many steps of
      this procedure using the juvenile tissue explants have been improved. Abundant
      availability of starting material and relative simplicity make this procedure an
      attractive choice for many researchers despite transformation efficiency that is
      in the low range of about 1%. Variety of available Agrobacterium strains and
      reporter/selection genes further facilitate the work by allowing careful planning
      of experiments in which many steps can be adjusted towards a particular Citrus
      cultivar. With the use of this procedure, genetically transformed grapefruit,
      oranges, lime, and rootstock cultivars are routinely produced while some
      difficulties persist in efforts to transform lemon and especially mandarin
      cultivars.

PMID- 17033063
TI  - Coffee (Coffea sp.).
AB  - Coffee (Coffea sp.) is a perennial plant widely cultivated in many tropical
      countries. It is a cash crop for millions of small farmers in these areas. As
      compared with other tree species, coffee has long breeding cycles that make
      conventional breeding programs time consuming. For that matter, genetic
      transformation can be an effective technique to introduce a desired trait in an
      already "elite" variety, or to study a gene function and expression. In this
      chapter, we describe two Agrobacterium-mediated transformation techniques; the
      first with A. tumefaciens to introduce an insect resistance gene and the second
      with A. rhizogenes to study candidate gene expression for nematode resistance in
      transformed roots.

PMID- 17033064
TI  - Papaya (Carica papaya L.).
AB  - Transgenic papaya plants were initially obtained using particle bombardment, a
      method having poor efficiency in producing intact, single-copy insertion of
      transgenes. Single-copy gene insertion was improved using Agrobacterium
      tumefaciens. With progress being made in genome sequencing and gene discovery,
      there is a need for more efficient methods of transformation in order to study
      the function of these genes. We describe a protocol for Agrobacterium-mediated
      transformation using carborundum-wounded papaya embryogenic calli. This method
      should lead to high-throughput transformation, which on average produced at least
      one plant that was positive in polymerase chain reaction (PCR), histochemical
      staining, or by Southern blot hybridization from 10 to 20% of the callus clusters
      that had been co-cultivated with Agrobacterium. Plants regenerated from the
      callus clusters in 9 to 13 mo.

PMID- 17033065
TI  - Pineapple [Ananas comosus (L.) Merr].
AB  - A procedure for pineapple [Ananas comosus (L.) Merr.] genetic transformation is
      described, which involves temporary immersion bioreactors (TIB) for selection of
      transgenic plants. Success in the production of transgenic pineapple plants
      combines tissue culture factors. Firstly, the use of regenerable pineapple callus
      as starting material for transformation whose cells shown to be competent for
      Agrobacterium infection. Secondly, the used of filtered callus, resulting in
      homogeneously sized clusters, thereby increasing the contact between the cell
      surfaces and A. tumefaciens and releasing phenolic compounds which induce
      Agrobacterium virulence. Thirdly, regeneration of primary plants without
      selection pressure, that allowing a massive production of putative transgenic
      pineapples. Finally, we support that TIB technology is a powerful system to
      recover nonchimera transgenic plants by micropropagation with the use of an
      adequate selection agent.

PMID- 17033066
TI  - Sugarcane (Saccharum spp.).
AB  - We describe the procedures for recovering transgenic sugarcane from co
      cultivation of both calli and in vitro plants with Agrobacterium tumefaciens. The
      correct tissue culture strategies and the use of super-binary vector or super
      virulent strain are crucial for the successful sugarcane transformation. Both
      plant regeneration via calli culture and micropropagation strategies can be
      optimized to a wide spectrum of sugarcane genotypes, thus the procedures
      presented here could be applied to genetic engineering of Saccharum spp. after
      minor modifications. For the case of sugarcane transformation using in vitro
      plants, four selective micropropagation steps must be sufficient to eliminate
      chimera plants.

PMID- 17033067
TI  - American Chestnut [Castanea dentata (Marsh.) Borkh].
AB  - The key to successful transformation of American chestnut is having the correct
      combination of explant tissue, selectable and scorable markers, and a reliable
      regeneration system. Rapidly dividing somatic embryos, growing as proembryogenic
      masses, are a suitable tissue; the bar gene is a suitable selectable marker in
      conjunction with 1.0 to 10 mg/L phosphirothricin (PPT); and the mgfp5-ER gene is
      an effective nondestructive scorable marker. We have also found that the more
      gently the somatic embryos are treated during the inoculation and co-cultivation
      steps, the higher the transformation efficiency. The average transformation
      efficiency that can be expected using the described protocol is approx 20 stable
      and embryogenic transformation events/g of somatic embryo tissue. Cell line and
      batch-to-batch deviations both upward and downward should be expected. Finally,
      somatic embryos can be induced to form shoots, which can then be micropropagated
      and acclimatized.

PMID- 17033068
TI  - Apple (Malus x domestica).
AB  - Apple (Malus x domestica) is one of the most consumed fruit crops in the world.
      The major production areas are the temperate regions, however, because of its
      excellent storage capacity it is transported to distant markets covering the four
      corners of the earth. Transformation is a key to sustaining this demand -
      permitting the potential enhancement of existing cultivars as well as to
      investigate the development of new cultivars resistant to pest, disease, and
      storage problems that occur in the major production areas. In this paper we
      describe an efficient Agrobacterium tumefaciens-mediated transformation protocol
      that utilizes leaf tissues from in vitro grown plants. Shoot regeneration is
      selected with kanamycin using the selectable kanamycin phosphotransferase
      (APH(3)II) gene and the resulting transformants confirmed using the scorable uidA
      gene encoding the bacterial beta-glucuronidase (GUS) enzyme via histochemical
      staining. Transformed shoots are propagated, rooted to create transgenic plants
      that are then introduced into soil, acclimatized and transferred to the
      greenhouse from where they are taken out into the orchard for field-testing.

PMID- 17033069
TI  - Blueberry (Vaccinium corymbosum L.).
AB  - Recent advances in plant biotechnology have led to a reliable and reproductive
      method for genetic transformation of blueberry. These efforts built on previous
      attempts at transient and stable transformation of blueberry that demonstrated
      the potential of Agrobacterium tumefaciens-mediated transformation, and as well,
      the difficulties of selecting and regenerating transgenic plants. As a
      prerequisite for successful stable transformation, efficient regeneration systems
      were required despite many reports on factors controlling shoot regeneration from
      leaf explants. The A. tumefaciens-mediated transformation protocol described in
      this chapter is based on combining efficient regeneration methods and the results
      of A. tumefaciens-mediated transient transformation studies to optimize selected
      parameters for gene transfer. The protocol has led to successful regeneration of
      transgenic plants of four commercially important highbush blueberry cultivars.

PMID- 17033070
TI  - Grapevine (Vitis vinifera L.).
AB  - Grapevine (Vitis) is considered to be one of the major fruit crops in the world
      based on hectares cultivated and economic value. Grapes are used not only for
      wine but also for fresh fruit, dried fruit, and juice production. Wine is by far
      the major product of grapes and the focus of this chapter is on wine grape
      cultivars. Grapevine cultivars of Vitis vinifera L. have a reputation for
      producing premium quality wines. These premium quality wines are produced from a
      small number of cultivars that enjoy a high level of consumer acceptance and are
      firmly entrenched in the market place because of varietal name branding and the
      association of certain wine styles and regions with specific cultivars. In light
      of this situation, grapevine improvement by a transgenic approach is attractive
      when compared to a classical breeding approach. The transfer of individual traits
      as single genes with a minimum disruption to the original genome would leave the
      traditional characteristics of the cultivar intact. However, a reliable
      transformation system is required for a successful transgenic approach to
      grapevine improvement. There are three criteria for achieving an efficient
      Agrobacterium-mediated transformation system: (1) the production of highly
      regenerative transformable tissue, (2) optimal co-cultivation conditions for both
      grapevine tissue and Agrobacterium, and (3) an efficient selection regime for
      transgenic plant regeneration. In this chapter, we describe a grapevine
      transformation system which meets the above mentioned criteria.

PMID- 17033071
TI  - Strawberry (Fragaria x ananassa).
AB  - Genetic transformation in strawberry (Fragaria spp.) can be achieved by using the
      Agrobacterium-mediated procedure on leaves from in vitro proliferated shoots.
      Regardless of the sufficient regeneration levels achieved from leaf explants of
      some commercial strawberry genotypes, the regeneration of transformed strawberry
      plants remains difficult and seems to be strongly genotype dependent. In fact,
      the main factors that play an important role in the success of strawberry genetic
      transformation are the availability of both an efficient regeneration protocol
      and an appropriate selection procedure of the putative transgenic shoots. The
      strawberry genetic transformation protocol herein described relates to two
      genotypes resulting from our experience with the highest regeneration and
      transformation efficiency. The study includes an octoploid Fragaria x ananassa
      cultivar (Sveva) and a diploid F. vesca cultivar (Alpina W.O.). All the different
      steps related to the leaf tissue Agrobacterium infection, co-culture, and
      selection of regenerating adventitious shoots, as well as the following
      identification of selected lines able to proliferate and root on the selective
      agent (kanamycin), will be described.

PMID- 17033072
TI  - Walnut (Juglans).
AB  - Walnut species are important nut and timber producers in temperate regions of
      Europe, Asia, South America, and North America. Trees can be impacted by
      Phytophthora, crown gall, nematodes, and cherry leaf roll virus; nuts can be
      severely damaged by codling moth and Xanthomonas blight. The long-generation time
      of walnuts and an absence of identified natural resistance for most of these
      problems suggest biotechnological approaches to crop improvement. Described here
      is a somatic embryo based transformation protocol that has been used to
      successfully insert horticulturally useful traits into walnut. Selection is based
      on the combined use of the selectable neomycin phosphotransferase (nptII) gene
      and the scorable uidA gene. Transformed embryos can be germinated or
      micropropagated and rooted for plant production. The method described has been
      used to establish field trials of mature trees.

PMID- 17033073
TI  - Carnation (Dianthus caryophylus L.).
AB  - Carnation is a valuable crop for the cut flower industry and demand for new and
      improved varieties is growing. However, genetic transformation of carnations is
      currently limited because of a lack of efficient routine technique. In this
      chapter, we present an easy and effective protocol for gene transfer to carnation
      node explants and subsequent adventitious shoot regeneration. For high
      adventitious shoot regeneration, node explants from first to third node of 5- to
      8-cm long shoots were cultured on Murashige and Skoog (MS) medium, containing 1.0
      mg/Lthidiazuron (TDZ), 0.1 mg/L alpha-napthalenoacetic acid (NAA), 20 g/L
      sucrose, and 2 g/L Gellan gum for 10 d. Then the explants were cut into 8 radial
      segments and subcultured onto MS medium, containing 1.0 mg/L BA, 0.1 mg/L NAA, 20
      g/L sucrose and 2 g/L Gellan Gum. For effective genetic transformation, 3- to 5-d
      precultured node explants were submerged in an Agrobacerium suspension for 10
      min, then cocultivated on filter paper soaked with water and 50 microM
      acetosyringone (AS). After cocultivation, the explants were cut into eight radial
      segments and subcultured onto selection medium until transformed shoots
      regenerated from the explants.

PMID- 17033074
TI  - Chrysanthemum (Dendranthema x grandiflora).
AB  - This chapter provides reproducible methods for the transformation of Dendranthema
      x grandiflora 'Shuhou-no-chikara' (standard) and 'Lineker' (spray) stem internode
      thin cell layers (TCLs) and conventional stem internode explants using
      Agrobacterium strains carrying a binary vector with beta-glucoronidase (GUS)
      reporter and nptII selector genes. Transformation efficiencies are reported at
      the kanamycin selection (callus formation and plantlet rooting), GUS assay,
      polymerase chain reaction (PCR), and Southern analysis levels. Notes on
      regeneration improvement through the use of TCLs, as well as the effective use of
      sonication for both regeneration and generation of transformants, stimulation of
      Agro-infection and elimination of Agrobacterium, are included.

PMID- 17033075
TI  - Orchids (Cymbidium spp., Oncidium, and Phalaenopsis).
AB  - Recent advances in genetic engineering have made the transformation and
      regeneration of plants into a powerful tool for orchid improvement. This chapter
      presents a simple and reproducible Agrobacterium tumefaciens-mediated
      transformation protocol and molecular screening technique of transgenics for two
      orchid species, Oncidium and Phalaenopsis. The target tissues for gene transfer
      were protocorm-like bodies (PLBs) derived from protocorms, into which constructed
      foreign genes were successfully introduced. To establish stable transformants,
      two stages of selection were applied on the PLBs co-cultivated with A.
      tumefaciens. About 10% transformation efficiency was achieved in Oncidium orchid,
      as 108 antibiotic resistant independent PLBs were proliferated from 1000 infected
      PLBs. In Phalaenopsis orchid about 11 to 12% of transformation efficiency was
      achieved by using the present protocol. Different molecular methods and GUS
      staining used to screen putative transgenic plants to confirm the integration of
      foreign DNA into the orchid genome were also described in detail. The methods
      described would also be useful for transformation of desired genes into other
      orchid species.

PMID- 17033076
TI  - Petunia (Petunia hybrida).
AB  - Petunia hybrida genetic transformation continues to be a valuable tool for
      genetic research into biochemical pathways and gene expression, as well as
      generating commercial products with varying floral colors. In this chapter, we
      describe a simple and reproducible genetic transformation protocol for generating
      transgenic petunia plants harboring a gene of interest and selectable marker. The
      system utilizes Agrobacterium tumefaciens for transgene integration with plant
      recovery via shoot organogenesis from leaf explant material. Selection for
      transgenic plants is achieved using the bar gene conferring resistance to
      glufosinate or nptII gene for resistance to kanamycin. Transformation
      efficiencies of around 10% are achievable with shoots being recovered about 8 wk
      after transgene insertion and rooted plants transferred to the greenhouse about
      twelve weeks after inoculation.

PMID- 17033077
TI  - Rose (Rosa hybrida L.).
AB  - Although rose transformation is successful, it remains difficult to transform
      myriad rose species as well as different rose genotypes. In this protocol, a
      detailed description of rose transformation is presented. This protocol relied on
      Agrobacterium-mediated transfer of embryogenic callus cultures. There are many
      critical steps that must be followed to achieve successful transformation;
      however, it is important to keep in mind that these apply to a selected number of
      genotypes, and as a different genotype is subjected to transformation,
      modifications of this protocol must be made to achieve successful transformation.

PMID- 17033078
TI  - Ginseng (Panax ginseng).
AB  - Genetic transformation is an attractive way to improve Panax ginseng C. A. Meyer
      by introducing new genetic materials and altering metabolic pathways that
      regulating the production of secondary compounds. In P. ginseng, production of
      transgenic plants via Agrobacterium tumefaciens is performed via somatic
      embryogenesis using cotyledon or embryogenic callus as explants. This chapter
      introduces the protocol of A. tumefaciens mediated-genetic transformation in P.
      ginseng.

PMID- 17033079
TI  - Hemp (Cannabis sativa L.).
AB  - Hemp (Cannabis sativa L.) suspension culture cells were transformed with
      Agrobacterium tumefaciens strain EHA101 carrying the binary plasmid pNOV3635. The
      plasmid contains a phosphomannose isomerase (PMI) selectable marker gene. Cells
      transformed with PMI are capable of metabolizing the selective agent, mannose,
      whereas cells not expressing the gene are incapable of using the carbon source
      and will stop growing. Callus masses proliferating on selection were screened for
      PMI expression using a chlorophenol red assay. Genomic DNA was extracted from
      putatively transformed callus lines and the presence of the PMI gene was
      confirmed using polymerase chain reaction and Southern hybridization. Using this
      method, an average transformation frequency of 31.23% +/- 0.14 was obtained for
      all transformation experiments, with a range of 15.1 to 55.3%.

PMID- 17033080
TI  - Opium Poppy (Papaver somniferum).
AB  - The genetic transformation of opium poppy, Papaver somniferum, offers the
      opportunity to study the mechanisms involved in the regulation of
      benzylisoquinoline and morphinan alkaloid biosynthesis. The development of an
      efficient transformation protocol for opium poppy has allowed us to transform a
      range of genotypes from all around the world, including previously recalcitrant
      high-yielding commercial Australian cultivars. The method involves Agrobacterium
      tumefaciens infection of hypocotyl explants, followed by the production of
      antibiotic or herbicide resistant embryogenic callus, the subsequent induction of
      somatic embryos and development into normal plants. The use of different
      selective agents, binary vectors, and poppy genotypes has demonstrated the
      robustness and reliability of this protocol in the production of many hundreds of
      confirmed transgenic poppies.

PMID- 17033081
TI  - Actinomycetes (Streptomyces lividans).
AB  - Agrobacterium tumefaciens is best known for its ability to transform plants by
      delivering the T-DNA that is processed and transferred from the resident Ti
      plasmid to the recipient plant cells. Less well known is the capacity of this
      Gram-negative bacterium to transfer its T-DNA into fungi and actinomycetes.
      Procedures are described on the use of the promiscuous T-DNA transfer system of
      A. tumefaciens to transform members of the actinomycetes. Integration of the T
      DNA derivatives into the Streptomyces chromosome provides opportunities of
      obtaining valuable mutants of this antibiotic producing soil organism.

PMID- 17033082
TI  - Filamentous Fungi (Magnaporthe grisea and Fusarium oxysporum).
AB  - A better understanding of fungal biology will facilitate judicious use of
      beneficial fungi and will also advance our efforts to control pathogenic fungi.
      Molecular studies of fungal biology have been greatly aided by transformation
      mediated mutagenesis techniques. Transformation via nonhomologous integration of
      plasmid DNA bearing a selectable marker (e.g., antibiotic resistance gene) has
      been widely used for the random insertional mutagenesis of fungi - as an
      alternative to chemical and radiation mutagens - mainly because the integration
      of plasmid into the genome provides a convenient tag for subsequent
      identification and isolation of the mutated gene. Homologous recombination
      between a target gene on the chromosome and the introduced DNA carrying its
      mutant allele results in targeted gene knock-out. An important advance in fungal
      transformation methodology is the development of Agrobacterium tumefaciens
      mediated transformation (ATMT) protocols for fungi. ATMT has been successfully
      applied to a phylogenetically diverse group of fungi and offers a number of
      advantages over conventional transformation techniques in both the random
      insertional mutagenesis and targeted gene knock-out. In this chapter, we describe
      ATMT protocols and vectors for fungal gene manipulation using two plant
      pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum, as target organisms.

PMID- 17033083
TI  - Green Alga (Chlamydomonas reinhardtii).
AB  - This protocol describes the Agrobacterium tumefaciens-mediated nuclear
      transformation of a microalgae Chlamydomonas reinhardtii, using a gene construct
      carrying the genes coding for beta-glucuronidase (gus), green fluorescent protein
      (gfp), and hygromycin phosphotransferase (hpt). The transformation frequency with
      this protocol as revealed by hygromycin resistance was many fold higher (about 50
      fold) than that of the commonly used glass bead method of transformation. The
      simplicity of Agrobacterium-mediated gene transfer and the high transformation
      frequency as well as the precision of T-DNA integration will enable further
      molecular dissection of this important model organism as well as other algal
      systems to understand basic plant metabolic processes as well as to exploit the
      systems for biotechnological applications.

PMID- 17033084
TI  - Mammalian cells.
AB  - Agrobacterium most likely can transform virtually all known plant species, and
      experimental protocols for Agrobacterium-mediated genetic transformation of yet
      more plant species, ecotypes, and cultivars are published almost on a daily
      basis. Interestingly, the Agrobacterium host range is not limited to the plant
      kingdom, and it has been shown to transform many species of fungi and even
      prokaryotes. The ability of Agrobacterium to genetically transform HeLa cells
      further widens the range of potential hosts of Agrobacterium to include humans
      and perhaps other animal species. Furthermore, because mammalian cells
      significantly differ from plant cells, they provide a useful experimental system
      for identification and functional characterization of plant-specific factors
      involved in the transformation process. Here, we present basic procedures for
      transfection and Agrobacterium-mediated genetic transformation of mammalian
      cells. We also demonstrate the use of mammalian cells for studies of the cellular
      components of the genetic transformation pathway.

PMID- 17033085
TI  - Mushroom (Agaricus bisporus).
AB  - We have devised an easy and effective genetic transformation method for the
      preeminent edible mushroom, Agaricus bisporus. Our method exploits the T-DNA
      transfer mechanism in Agrobacterium tumefaciens and relies on the reproductive
      fruiting body as the recipient tissue. The use of fruiting body explants,
      particularly the gill, provided high-frequency transformation, overcoming the
      inefficacy of Agrobacterium-based methods targeting fungal spores or vegetative
      mycelium. The protocol entails incubation of A. tumefaciens for 3 h with
      acetosyringone, a signaling molecule that launches the gene transfer mechanism,
      co-cultivation of the induced bacterium and gill explants for 3 d, and selection
      for transformants based on an inherited resistance to the antibiotic hygromycin.
      Between 7 and 28 d on the selection medium, upwards of 95% of the gill explants
      generate hygromycin-resistant colonies. About 75% of the mushroom transformants
      show a single-copy of the hygromycin-resistant gene integrated at random sites in
      the genome.

PMID- 17033086
TI  - Yeast (Saccharomyces cerevisiae).
AB  - The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic
      organisms. This species has enabled a detailed study of the (genetic)
      requirements for Agrobacterium-mediated DNA transformation. For instance research
      with this yeast has led to the recognition that the transforming DNA molecules
      integrate into the eukaryotic chromosomes either by homologous recombination,
      which is the preferred pathway in S. cerevisiae, or by nonhomologous end-joining.
      Based on the protocol for Agrobacterium-mediated transformation of S. cerevisiae
      methodology has been developed for the transformation of many other yeast and
      fungal species.

PMID- 17033087
TI  - Potential involvement of a propranolol-insensitive atypical beta-adrenoceptor the
      vasodilator effect of cyanopindolol in the human pulmonary artery.
AB  - The aim of our study was to examine whether non beta(1)-/beta(2)-adrenoceptors
      participate in the relaxation of the human pulmonary artery. For this purpose the
      vasodilatory effect of the non-conventional partial beta-adrenoceptor agonist
      cyanopindolol was examined. Cyanopindolol (1-300 microM), studied in the presence
      of the beta(1)-/beta(2)-adrenoceptor antagonist propranolol, relaxed the human
      pulmonary artery preconstricted with serotonin 1 microM in a concentration
      dependent manner (maximally by about 80%). This effect was diminished by
      bupranolol 10 microM (an antagonist of beta(1)-beta(3)-adrenoceptors and the low
      affinity state of the beta(1)-adrenoceptor) and CGP 20712 10 microM (known to
      antagonize the low-affinity state of the beta(1)-adrenoceptor at high
      concentrations). In further experiments, the effect of beta-adrenoceptor ligands
      on the serotonin-induced vasoconstriction was examined. The concentration
      response curve for serotonin was not affected by cyanopindolol 30 microM,
      bupranolol 10 microM and CGP 20712 10 microM but shifted to the right by
      cyanopindolol 100 and 300 microM; the serotonin 5-HT(2A) receptor antagonist
      ketanserin 0.3 microM abolished the maximum contraction elicited by serotonin. In
      conclusion, the present study reveals that the vasodilatory effect of
      cyanopindolol in the human pulmonary artery consists of two components, i.e.
      activation of a propranolol-insensitive atypical beta-adrenoceptor and antagonism
      against 5-HT(2A) receptors.

PMID- 17033088
TI  - Cerebroprotective effect of angiotensin IV in experimental ischemic stroke in the
      rat mediated by AT(4) receptors.
AB  - Recent studies have reported potential roles of angiotensins in an adaptative
      physiological mechanism of protection against cerebral ischemia-induced
      neurological damages. In the present study, we examined the protective role of
      angiotensin IV (AngIV) in a rat model of embolic stroke induced by intracarotid
      injection of calibrated microspheres (50 microm). Internal carotid infusions of
      increasing doses of AngIV (0.01, 0.1 and 1 nmol/0.1 mL saline) dose dependently
      decreased mortality, neurological deficit and cerebral infarct size at 24 hours.
      With the highest dose of AngIV, mortality was reduced from 55 % in saline infused
      controls to 10 % (p=0.003), neurological deficit was reduced from 3.8 +/- 0.3 to
      1.4 +/- 0.3 , (p<0.0001) and cerebral infarct size at 24 hours was decreased from
      432 +/- 26 mm(3) to 185 +/- 19, (p=0.0001). The AT(4) antagonist divalinal-AngIV
      (10(-9) mol/0.1 mL), or pretreatment with L-NAME (10(-7) mol/0.1 mL), both
      completely abolished the protective effect of AngIV (1 nmol). The AT(2)
      antagonist PD123319 (10(-7) mol/0.1 mL) partially prevented the protective effect
      of AngIV on the neurological score. Sequential cerebral arteriographies revealed
      that AngIV induced a redistribution of blood flow to the ischemic areas within
      minutes. These results suggest that pharmacological doses of AngIV are protective
      against acute cerebral ischemia by triggering an AT(4)-mediated, NO-dependent
      intracerebral hemodynamic mechanism.

PMID- 17033089
TI  - Increased reactive oxygen species contributes to kidney injury in
      mineralocorticoid hypertensive rats.
AB  - Hypertension is associated with increased reactive oxygen species (ROS). Renal
      ROS production and their effects on renal function have never been investigated
      in mineralocorticoid hypertensive rats. In this study we hypothesized that
      increased ROS production in kidneys from deoxycorticosterone (DOCA)-salt rats
      contributes to adverse renal morphological changes and impaired renal function in
      DOCA-salt hypertensive rats. We also determined whether ROS-induced renal injury
      was dependent on blood pressure. DOCA-salt hypertensive rats exhibited a marked
      increase in blood pressure, renal ROS production, glomerular and tubular lesions,
      and microalbuminuria compared to sham rats. Treatment of DOCA-salt hypertensive
      rats with apocynin for 28 days resulted in attenuation of systolic blood pressure
      and improvement of renal morphology. Renal superoxide level in DOCA-salt rats was
      215% of sham-operated rats and it was significantly decreased to 140% with
      apocynin treatment. Urinary protein level was decreased from 27 +/- 3 mg/day in
      DOCA-salt hypertensive rats to 9 +/- 2 mg/day. 28 days of Vitamin E treatment
      also reduced renal injury in regard to urinary protein level and renal morphology
      but had no effect on blood pressure in DOCA-salt rats. Increased urinary 8
      isoprostane, a marker for oxidative stress, in DOCA-salt hypertensive rats (55 +/
      8 ng/day) was diminished by vitamin E treatment (24 +/- 6 ng/day). These data
      suggest that renal injury characteristic of mineralocorticoid hypertension is
      associated with oxidative stress and is partly independent of blood pressure.

PMID- 17033090
TI  - Inhibitory effect of Ca(2+) on ATP-mediated stimulation of NPR-A-coupled guanylyl
      cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats.
AB  - Atrial natriuretic peptide (ANP) regulates blood pressure mainly through the
      occupation of the guanylyl cyclase-coupled receptor NPR-A, which requires ATP
      interaction for maximal activation. This study investigates the effect of
      extracellular Ca(2+) on ATP-mediated regulation of NPR-A-coupled guanylyl cyclase
      activity in glomerular membranes from Wistar Kyoto (WKY) and spontaneously
      hypertensive rats (SHR). ATP induced a significant increase in basal and ANP(1
      28)-stimulated guanylyl cyclase activity that was greater in SHR than in WKY.
      Extracellular Ca(2+) inhibited ATP-stimulated guanylyl cyclase activity in a
      concentration-dependent manner, but did not modify basal and ANP(1-28)-stimulated
      guanylyl cyclase activity. In the presence of ATP, NPR-A showed higher affinity
      for ANP(1-28) and lower Bmax. Ca(2+) did not modify NPR-A-ANP(1-28) binding
      properties. The different effects of extracellular Ca(2+) on ANP(1-28)- or ATP
      mediated guanylyl cyclase activation suggest that these events are differentially
      regulated. Addition of extracellular Ca(2+) induced similar effects in
      hypertensive and normotensive rats, suggesting that it is not responsible for the
      elevated cGMP production observed in SHR.

PMID- 17033091
TI  - Upregulation of angiotensin AT1a receptors mRNA in the heart and renal medulla
      after myocardial infarction in rats.
AB  - The myocardial infarct causes prolonged activation of the renin-angiotensin
      system and profoundly influences cardiac performance and renal excretory
      capabilities. The aim of the present study was to determine whether the
      myocardial infarct is also associated with an altered expression of AT1a
      receptors (AT1aR) mRNA in the heart and the kidney. To this end male Sprague
      Dawley rats were subjected either to the left coronary artery ligation or to the
      sham surgery. Four weeks after the surgery the animals were sacrificed. In 11
      infarcted and 10 sham-operated rats expression of AT1aR mRNA in the walls of the
      left and right ventricle of the heart, and in the renal cortex and renal medulla
      was determined by semiquantitative PCR method. In another group of 10 infarcted
      and 14 sham-operated rats the diameter of cardiomyocytes in the left and right
      cardiac ventricle was determined. The size of the infarct in the rats used for
      mRNA determination and for morphometric measurements was equal to 29.4 +/- 1.8%
      and to 31.0 +/- 1.2 % of the left ventricular wall, respectively. Expression of
      AT1aR mRNA was significantly greater in the left (P< 0.01) and right ventricle
      (P<0.03) of the heart in the infarcted than in the sham operated rats. AT1aR mRNA
      expression was also significantly greater (P<0.02) in the renal medulla of the
      infarcted rats than in the renal medulla of the sham operated rats whereas no
      significant difference was found in the renal cortex. The myocardial infarct was
      associated with a significant increase of diameter of cardiomyocytes of the left
      ventricle of the heart (P< 0.0001), however there was no significant correlation
      between changes in AT1aR mRNA expression and diameter of cardiomyocytes. The
      results provide evidence that the myocardial infarct results in significant and
      prolonged upregulation of AT1a receptors mRNA expression in the heart and in the
      medullary region of the kidney.

PMID- 17033092
TI  - Imipramine and citalopram reverse corticosterone-induced alterations in the
      effects of the activation of 5-HT(1A) and 5-HT(2) receptors in rat frontal
      cortex.
AB  - Using extracellular recording we studied changes in the reactivity of rat frontal
      cortical slices to the 5-HT(1A), 5-HT(2) and 5-HT(4) receptor agonists, (+/-)-2
      dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT),
      (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride,
      respectively, induced by an earlier treatment of animals with corticosterone
      lasting 1 or 3 weeks. Spontaneous bursting activity was recorded in ex vivo
      slices incubated in a medium devoid of Mg(2+) ions and containing picrotoxin (30
      microM). Repetitive, but not single, corticosterone administration resulted in an
      attenuation of the effect of the activation of 5-HT(1A) receptors and in an
      enhancement of the effect related to 5-HT(2) receptors. The effect of 5-HT(4)
      receptor activation remained unchanged. In separate two sets of experiments rats
      were treated with corticosterone for 3 weeks and additionally with imipramine or
      citalopram, beginning on the eighth day of corticosterone administration. In the
      corticosterone plus imipramine as well as corticosterone plus citalopram groups
      the effects of 8-OH-DPAT and DOI were not different from control indicating that
      corticosterone-induced functional modifications in the reactivity of 5-HT(1A) and
      5-HT(2) receptors were reversed by antidepressant treatments.

PMID- 17033094
TI  - Effects of tyrosine kinase inhibitors on voltage-dependent Ba(2+) currents in the
      guinea-pig gastric antrum.
AB  - We have investigated whether tyrosine kinases modify the activity of voltage
      dependent Ba(2+) currents (I(Ba)) recorded from guinea-pig gastric myocytes by
      use of patch-clamp techniques. All experiments were carried on single smooth
      muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum.
      Genistein ( > or = 10 microM), a specific tyrosine kinase inhibitor, reduced the
      peak amplitude of I(Ba) in a voltage- and concentration-dependent manner.
      Daidzein ( > or = 30 microM), an inactive analog of genistein, also inhibited
      I(Ba) in a concentration-dependent manner. Similarly, other types of tyrosine
      kinase inhibitors (lavendustin A and tyrphostin 23) suppressed the peak amplitude
      of I(Ba) in a concentration-dependent manner. These results indicate that
      tyrosine kinases may be essential to regulate Ca(2+) mobilization through voltage
      dependent Ca(2+) channels in gastric myocytes.

PMID- 17033093
TI  - Comparison of gene expression profiles in neuropathic and inflammatory pain.
AB  - Molecular mechanisms underlying the differences between chronic neuropathic and
      inflammatory pain are still poorly understood. Identifying those differences
      should provide insight into the molecular mechanism underlying features unique
      for neuropathic pain, such as allodynia. We have performed screening for
      differentially expressed genes in the spinal cord in the rat models of
      neuropathic and inflammatory pain. Using BD Atlas Rat 4K arrays we found several
      differences in expression of secretion-related genes between inflammatory and
      neuropathic pain. Development of the latter was characterized by up-regulated
      expression of genes associated with immune response and microglia activation and
      also, to a lesser extent, with cytoskeleton rearrangement. The relative increase
      in abundance of four genes, intercellular adhesion molecule 1 (ICAM-1),
      calcitonin gene related peptide (CGRP), tissue inhibitor of metalloproteinase 1
      (TIMP-1), chemokine-like receptor 1 was confirmed by reverse transcription Real
      Time PCR (qPCR) validation in the spinal cord in neuropathic pain. Levels of
      transcripts corresponding to ICAM-1 and TIMP-1 were also increased in the dorsal
      root ganglia (DRG) of neuropathic rats. Our data point at the importance of
      immune response- and microglia activation-related genes in the development of
      chronic neuropathic pain, and suggest that expression of CGRP gene in the dorsal
      horn of the spinal cord could be involved in persistence of its symptoms.

PMID- 17033095
TI  - Influence of ghrelin on gastric and duodenal growth and expression of digestive
      enzymes in young mature rats.
AB  - Ghrelin, a nature ligand for the growth hormone secretagogue receptor (GHS-R),
      stimulates a release of growth hormone, prolactin and adrenocorticotropic
      hormone. Also, ghrelin increases food intake in adult rats and humans and
      exhibits gastroprotective effect against experimental ulcers induced by ethanol
      or stress. The aim of present study was to examine the influence of ghrelin
      administration on gastric and duodenal growth and expression of pepsin and
      enterokinase in young mature rats with intact or removed pituitary. METHODS: Two
      week after sham operation or hypophysectomy, eight week old Wistar male rats were
      treated with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose) i.p. twice a
      day for 4 days. Expression of pepsin in the stomach and enterokinase in the
      duodenum was evaluated by real-time PCR. RESULTS: In animals with intact
      pituitary, treatment with ghrelin increased food intake, body weight gain and
      serum level of growth hormone and insulin-like growth factor-1 (IGF-1). These
      effects were accompanied with stimulation of gastric and duodenal growth. It was
      recognized as the significant increase in gastric and duodenal weight and mucosal
      DNA synthesis. In both organs, ghrelin administered at the dose of 8 nmol/kg
      caused maximal growth-promoting effect. In contrast to these growth-promoting
      effects, administration of ghrelin reduced expression of mRNA for pepsin in the
      stomach and was without effect on expression of mRNA for enterokinase in the
      duodenum. Hypophysectomy alone lowered serum concentration of growth hormone
      under the detection limit and reduced serum level of IGF-1 by 90%. These effects
      were associated with reduction in daily food intake, body weight gain and
      gastroduodenal growth. In hypophysectomized rats, administration of ghrelin was
      without significant effect on food intake, body weight gain or growth of
      gastroduodenal mucosa. Also, serum concentration of growth hormone or IGF-1 was
      not affected by ghrelin administration in rats with removed pituitary.
      CONCLUSION: Administration of ghrelin stimulates gastric and duodenal growth in
      young mature rats with intact pituitary, but inhibits expression of mRNA for
      pepsin in the stomach. Growth hormone and insulin-like growth factor-1 play an
      essential role in growth-promoting effects of ghrelin in the stomach and
      duodenum.

PMID- 17033096
TI  - Opioid agonist/antagonist effect of naloxone in modulating rabbit jejunum
      contractility in vitro.
AB  - Opioid peptides are the most effective drugs in controlling pain; their action is
      elicited by binding to specific membrane receptors. The gastrointestinal tract
      represents, after the nervous system, the site in which the opioid receptors are
      expressed at high levels. The opioid agonist morphine has a significant
      inhibitory effect on intestinal motility, this action is blocked by naloxone an
      opioid antagonist mainly active at mu and kappa receptors. In this study the
      presence of mu opioid receptor on rabbit jejunum was investigated by western
      blot. The effects of beta-endorphin, the endogenous opioid peptide with the
      highest affinity to the mu opioid receptor and those of naloxone on spontaneous
      rabbit jejunum contractions were evaluated. Beta-endorphin (10(-6) M) showed a
      relaxant effect on jejunum contractility while naloxone showed a dual effect
      inducing an increase of spontaneous contractility at low concentrations (10(-6)
      M, 10(-7) M, 10(-8) M) and a decrease when high concentrations (10(-3) M, 10(-4)
      M, 10(-5) M) were utilized. The obtained results demonstrate that mu opioid
      receptor is expressed in rabbit jejunum and suggest that this receptor may be
      involved in mediating the effects of both opioid agonist and antagonist on
      jejunum contractions.

PMID- 17033097
TI  - Angiotensins II and IV modulate adrenocortical cell proliferation in
      ovariectomized rats.
AB  - Effects of angiotensins II (AngII), angiotensin IV (AngIV, 3-8 fragment of
      angiotensin II) and losartan (an antagonist of angiotensin receptor type 1) on
      the proliferation of adrenocortical cells in ovariectomized rats have been
      studied. The incorporation of bromodeoxyuridine (BrdU) into cell nuclei was used
      as an index of cell proliferation. AngIV decreased BrdU labeling index mainly in
      the reticularis zone and losartan (Los) was able to partially reverse this
      inhibitory effect of AngIV. AngII had no effect on the adrenocortical cell
      proliferation when given alone, however Los given simultaneously diminished BrdU
      incorporation into nuclei of glomerulosa and reticularis zones as compared with
      AngII. These findings suggest that AngII and AngIV modulate adrenocortical cell
      proliferation in ovariectomized rats.

PMID- 17033098
TI  - The involvement of nitric oxide and prostaglandins in the cholinergic stimulation
      of hypothalamie-pituitary-adrenal response during crowding stress.
AB  - The aim of the present study was to determine the effect of social crowding
      stress and significance of nitric oxide (NO) and prostaglandins (PG) generated by
      constitutive and inducible nitric oxide synthase (NOS) and cyclooxygenase (COX)
      in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic
      muscarinic receptor agonist carbachol. Inhibitors of neuronal NOS (nNOS) L-NNA,
      general NOS L-NAME and inducible NOS (iNOS) aminoguanidine, as well as inhibitors
      of COX-1, piroxicam, and COX-2, compound NS-398 were administered 15 min prior to
      carbachol to control or crowded rats (24 rats in cage for 7, during 3 and 7
      days). In stressed rats L-NAME, L-NNA and aminoguanidine significantly
      intensified the carbachol-induced ACTH and corticosterone secretion, like in
      control rats. Piroxicam, markedly decreased the carbachol-induced ACTH and
      corticosterone response under either basal or stress conditions. Compound NS-398
      did not markedly alter the carbachol-induced HPA response in control and stressed
      rats. Crowding stress (3 days) significantly impaired the i.c.v. prostaglandin
      E(2)-induced ACTH response. Corticotropin releasing hormone (CRH) receptor
      antagonists, alpha-helical CRH [9-14], given i.c.v. did not alter the PGE(2)
      evoked corticosterone response in either control or stressed rats, indicating
      that hypothalamic CRH is not involved in the PGE(2)-induced central stimulation
      of HPA axis. In control rats L-NAME considerably enhanced, while L-arginine, a
      physiological NOS substrate, abolished the PGE(2)-induced ACTH and corticosterone
      response. In stressed rats this NOS blocker significantly increased and L-Arg
      reduced the stimulatory effect of PGE(2) on ACTH and corticosterone secretion.
      The carbachol-induced corticosterone response was significantly increased by
      pretreatment with nNOS inhibitor L-NNA and was considerably reduced by
      indomethacin, a general COX inhibitor. Pretreatment with both antagonists left
      the carbachol-induced corticosterone level unchanged, suggesting an independent
      and reciprocal effect of NO and PG in the cholinergic stimulation of pituitary
      adrenocortical response. These results indicate that in the stimulatory action of
      muscarinic agonist, carbachol, NO is an inhibitory transmitter under basal and
      crowding stress conditions. This psychosocial stress does not functionally affect
      the NOS/NO systems. Prostaglandins are involved in the cholinergic muscarinic
      induced stimulation of HPA response to a significant extent in non-stressed rats.
      PGE(2) may be involved in the carbachol-elicited HPA response under basal and
      stress conditions. Prostaglandins released in response to muscarinic stimulation
      did not evoke the hypothalamic CRH mediation. NO significantly impairs and PG
      stimulates the carbachol-induced HPA response in rats under basal and social
      stress conditions.

PMID- 17033099
TI  - The expression of short from of leptin receptor gene during early pregnancy in
      the pig examined by quantitative real time RT-PCR.
AB  - The study was conducted to determine gene expression of short form of leptin
      receptor (OB-Rs) using real time RT-PCR in distinct tissues of the central
      nervous system (medial basal hypothalamus, preoptic area, stalk median eminence),
      pituitary and reproductive tract (corpus luteum, ovarian stroma, endometrium,
      myometrium, and trophoblast) in pigs during luteal phase of the cycle and early
      gestation. The expression of OB-Rs mRNA in SME did not differ between analyzed
      stages of the cycle and pregnancy. In anterior pituitary, transcript levels were
      almost identical in mid- and late-luteal periods, but significantly decreased on
      30-32 day of gestation when compared with day 14-16. In posterior pituitary,
      significantly higher expression was observed in two periods of pregnancy when
      compared with two stages of luteal phase. In corpus luteum the lowest expression
      was observed during days 10-12 of the cycle, whereas markedly higher levels were
      detected in late-luteal stage and gestation. In ovarian stroma the expression of
      Ob-Rs mRNA was markedly diminished during days 14-16 of the cycle when compared
      with days: 10-12 of the cycle and 30-32 of pregnancy. The expression of Ob-Rs
      mRNA in endometrium and myometrium reached the lowest levels on 30-32 day of
      pregnancy in comparison with earlier stage, 14-16 day. Summarizing, the
      expression of the short form of leptin receptor mRNA was found in majority of
      tested tissues including hypothalamus, pituitary and reproductive tract and their
      levels fluctuated depending on the phase (mid- and late-luteal) of the cycle and
      the day of pregnancy (early and late stage of implantation).

PMID- 17033100
TI  - Interspecies differences in the force-frequency relationship of the medial
      gastrocnemius motor units.
AB  - Single, functionally isolated motor units were studied in the medial
      gastrocnemius (MG) muscle of cats and rats. Axons of their motoneurons were
      stimulated with trains of pulses at frequencies increasing from 1 to 150 Hz and
      forces developed by muscle fibers were measured and force-frequency curves were
      compared between species. The following observations were made: (1) the most
      steep parts of curves (related to unfused tetani of motor units) begun at lower
      frequencies of stimulations in all types of feline motor units, (2) for fast
      motor units, the same relative values of force of unfused tetani were achieved at
      significantly lower frequencies of stimulations in the cat than in the rat.
      Twitch time parameters of both species influenced the course of force-frequency
      curves. It was showed that the contraction times of feline units varied in the
      wide range (21-81 ms), and these units reached 60% of the maximum force at
      stimulation frequencies between 10 and 38 Hz. On the other hand, contraction
      times of rat units ranged from 10 to 34 ms, whereas stimulation frequencies
      necessary to reach 60% of the maximum force varied considerably, from 12 to 65
      Hz. The correlations between the above parameters were found for motor units of
      each species. However, the regression lines drown for the collected population of
      cat and rat units did not form linear continuity. Thus it seems that interspecies
      differences in the twitch contraction times do not fully explain different force
      frequency relationships in mammalian skeletal muscles.

PMID- 17033102
TI  - Helicobacter pylori: microbiology and interactions with gastrointestinal
      microflora.
AB  - Helicobacter pylori causes substantial morbidity and mortality, and the course of
      infection results from complex interactions between host, environmental and
      bacterial factors. It is generally accepted that H. pylori eradication is the
      best method of treatment for peptic ulcer disease and prevention of its
      complications. However, the antimicrobial agents used in eradication regimens
      cause various alterations in gastrointestinal microflora, which can lead to side
      effects affecting the patient's compliance. Moreover, antimicrobial therapy is
      responsible for increasing resistance not only in H. pylori but also in
      colonising microflora, and, therefore, alternative approaches to the treatment
      and prevention of H. pylori infection have been investigated.

PMID- 17033103
TI  - Interplay between Helicobacter pylori and the immune system. Clinical
      implications.
AB  - Helicobacter pylori (H. pylori) is a gram-negative bacteria infecting more than
      50% of human population. H. pylori selectively colonizes gastric mucosa and
      represents the major cause of gastroduodenal pathologies, such as gastric ulcer,
      autoimmune gastritis, gastric cancer and B cell lymphoma of mucosa associated
      lymphoid tissue (MALT). In this review interplay between H. pylori and both
      innate and adaptive immune responses is discussed. The second part of this
      article presents current knowledge about the relationship between H. pylori
      infection and neoplasia.

PMID- 17033104
TI  - Helicobacter pylori and its involvement in gastritis and peptic ulcer formation.
AB  - Modern gastroenterology started in early 19(th) century with the identification
      by W. Prout of the inorganic (hydrochloric) acid in the stomach and continued
      through 20(th) century with the discoveries by I.P. Pavlov of neuro-reflex
      stimulation of gastric secretion for which he was awarded first Nobel Prize in
      1904. When concept of nervism or complete neural control of all digestive
      functions reached apogeum in Eastern Europe, on the other side of Europe (in
      United Kingdom), E. Edkins discovered in 1906 that a hormone, gastrin, may serve
      as chemical messenger in stimulation of gastric acid secretion, while L.
      Popielski revealed in 1916 that histamine is the most potent gastric
      secretagogue. K. Schwartz, without considering neural or hormonal nature of
      gastric secretory stimulation, enunciated in 1910 famous dictum; "no acid no
      ulcer"; and suggested gastrectomy as the best medication for excessive gastric
      acid secretion and peptic ulcer. In early 70s, J.W. Black, basing on earlier L.
      Popielski's histamine concept, identified histamine-H(2) receptors (H(2)-R) and
      obtained their antagonists, which were found very useful in the control of
      gastric acid secretion and ulcer therapy for which he was awarded in 1972 second
      Nobel Prize in gastrology. With discovery by G. Sachs in 1973 of proton pumps and
      their inhibitors (PPI), even more effective in gastric acid inhibition and ulcer
      therapy than H(2)-R antagonists, gastric surgery, namely gastrectomy, practiced
      since first gastric resection in 1881 by L. Rydygier, has been considered
      obsolete for ulcer treatment. Despite of the progress in gastric pharmacology,
      the ulcer disease remained essentially "undefeated" and showed periodic
      exacerbation and relapses. The discovery of spiral bacteria in the stomach in
      1983 by B.J. Marshall and R.J. Warren, Australian, clinical researches, awarded
      in 2005 the Nobel Prize for the third time in gastrology, has been widely
      considered as a major breakthrough in pathophysiology of gastritis and peptic
      ulcer, which for the first time can be definitively cured by merely eradication
      of germ infecting stomach. This overview presents the mechanism of induction of
      gastritis and peptic ulcer by the H. pylori infection and describes accompanying
      changes in gastric acid and endocrine secretion as well as the effects of germ
      eradication on gastric secretory functions and gastroduodenal mucosal integrity.

PMID- 17033105
TI  - Gastric cancer and Helicobacter pylori infection.
AB  - The Nobel prize in Physiology and Medicine in 2005 was presented to Barry
      Marshall and Robin Warren for their discovery of Helicobacter pylori (Hp), but
      only the involvement of this germ in gastritis and peptic ulcer has been
      mentioned in the award sentence, while numerous epidemiological, clinical and
      experimental studies and reports emphasized the crucial role of Hp in
      pathogenesis of gastric cancer (GC). This review is based on the old concept
      proposed by P. Correa much before the discovery of spiral bacteria in the
      stomach, postulating the cascade of mucosal changes from acute/chronic gastritis
      into the atrophic gastritis with intestinal metaplasia and finally to dysplasia
      and GC. It is now widely accepted view that Hp infection is the major initiator
      of the inflammatory and atrophic changes in gastric mucosa accompanied by an over
      expression of certain growth factors such as gastrin as well as of cyclooxygenase
      2 (COX-2) and anti-apoptotic proteins including survivin and B-cl(2), leading to
      proliferation of mutated atrophic cells, excessive angiogenesis, inhibition of
      apoptosis and formation of gastric tumour. All the morphological and biochemical
      changes associated with the transformation of mucosal cells into the cancer cells
      can be traced in excellent experimental model of gastric cancerogenesis induced
      by infection of Hp in Mongolian gerbils. Since the eradication therapy was proved
      in several prospective clinical trials to greatly reduce the incidence of GC and
      this was confirmed on the gerbil model of Hp-induced GC, it has been postulated;
      a) that Hp is the major causal factor in pathogenesis of GC and b) that the only
      rational approach in attempt to reduce the occurrence of GC is the global
      eradication of Hp.

PMID- 17033106
TI  - Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter
      pylori in the stomach of humans and experimental animals.
AB  - Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drugs (NSAID)
      are major pathogenic factors in peptic ulcer disease but whether these two
      factors exert synergistic or antagonistic action on the gastric mucosa has been a
      subject of controversy. The classic concept states that there is an increased
      ulcer occurrence and bleeding in patients with both H. pylori infection and NSAID
      use. However, the question whether the H. pylori eradication therapy in NSAID
      users reduces the occurrence of peptic ulcer has not been fully addressed.
      Studies on secondary prevention of NSAID-associated ulcers in H. pylori patients
      have indicated that H. pylori eradication results in impaired ulcer healing with
      an effect on the rate of peptic ulcer occurrence. On the other hand, the
      treatment of H. pylori in patients with no prior history of chronic NSAID therapy
      has been shown to decrease the risk of peptic ulcer. Studies in experimental
      animals revealed for instance, that the H. pylori infection augments the gastric
      mucosal damage induced by NSAID in Mongolian gerbils. In rats with preexisting
      chromic gastric ulcers, H. pylori infection attenuated significantly the aspirin
      induced inhibition of ulcer healing and accompanying fall in the gastric blood
      flow at the margin of these ulcers, suggesting negative interaction between
      aspirin and H. pylori on ulcerogenesis. Accumulated evidence in humans and
      animals shows that both aspirin and H. pylori upregulate the expression of
      cyclooxygenase (COX)-2 both at mRNA and protein levels at the ulcer margin, but
      failed to influence significantly that of COX-1. It was, therefore, proposed that
      H. pylori may in fact, antagonize, aspirin-induced delay of ulcer healing due to
      suppression of acid secretion by the enhancement in PGE(2) possibly derived from
      COX-2 expression and activity and to the overexpression of growth factors such as
      TGF alpha and VEGF. The present review summarizes and further addresses the issue
      of the interaction between these two major ulcer risk factors determined in the
      stomach of humans and experimental animals.

PMID- 17033107
TI  - Helicobacter pylori infection in pathogenesis of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) refers to the very common and constantly
      increasing conditions where reflux of gastric contents into the esophagus leads
      to development of characteristic symptoms. The esophagus, LES and stomach can be
      envisioned as single functional unit controlled by neuro-hormonal factors. The
      abnormalities that contribute to GERD can start in any component of this unit,
      resulting particularly from disturbances in their control system. It is extremely
      important to identify factors and mechanisms leading to functional failure of
      this system so that causative therapy can be effectively applied. The key-role
      has been attributed to parasympathetic dysfunction, which may adversely affect
      motor activity of this area by increasing transient LES relaxation number and
      impairing LES pressure, esophageal acid clearance and motility of the proximal
      stomach. Recently, numerous investigations have been performed to elucidate the
      role of Helicobacter pylori (Hp) infection in GERD pathogenesis with the most
      concern given to its potency to increase gastric acid secretion. However, it
      appeared that this infection leads to much more complex changes in gastric mucosa
      including modification of afferent neural signals and specific gastric hormones
      release. Plasma ghrelin level is low in subjects infected and increases
      significantly after eradication. Since ghrelin, beside potency to increase
      gastric secretion has strong prokinetic action on LES functional unit, this
      phenomenon together with impaired vagal control may contribute to the Hp
      infection or eradication - related GERD development. Thus, ghrelin and vagal
      activity could be the missing links that partially explains relationship between
      GERD and Hp infection.

PMID- 17033108
TI  - The relationship between the presence of Helicobacter pylori in the oral cavity
      and gastric in the stomach.
AB  - There are numerous studies suggesting that inflammation of the oral cavity caused
      by bacteria or fungi is accompanied by gastric inflammation. This is particularly
      relevant in patients using complete dentures. Since the presence of H. pylori in
      the oral cavity can be easily discovered by bacteria culture and that in the
      stomach by (13)C urea breath test (UBT) and histology of gastric endoscopic
      biopsy samples it is reasonably to state that the majority of the patients show
      the presence of bacterium in oral cavity and active gastric H. pylori infection.
      When comparing, however, the bacteria culture originating from the oral mucosa to
      those from the gastric mucosa, employing molecular biology examination, such as
      polymerase chain reaction (PCR), we found that the oral bacteria and those
      originating from stomach are completely different, suggesting that H. pylori may
      be present only transiently in oral cavity and does not play major role in
      gastric H. pylori infection. Thus, oral cavity does not serve as bacterial
      reservoir to infect gastric mucosa. Most important finding of our study is that
      patients with recognized inflammation in the oral cavity in the form of
      stomatitis prothetica hyperplasica both fibrosa as well as papillaris showed in
      nearly 100% gastric H. pylori infection, usually without the presence of the same
      bacterium in the oral cavity, suggesting that gastric H. pylori infection affects
      oral mucosa at distance by some, as yet, unknown mechanism.

PMID- 17033109
TI  - Helicobacter pylori infection in coronary artery disease.
AB  - The role of inflammation in the pathogenesis and progression of coronary artery
      disease (CAD) has been increasingly discussed, but still remains unclear.
      Inflammatory changes in the vessel wall play an important role in the
      pathogenesis of atherosclerosis. Systemic inflammatory reaction can be detected
      by showing increased plasma levels of different proinflammatory cytokines and
      acute-phase proteins. Infectious agents have been linked to coronary heart
      disease on epidemiological and pathogenetic grounds. The prevalent condition and
      the exact mechanism of initiation of atherosclerotic vascular disease remain
      unclear. Nevertheless, many similarities exist between the processes of
      inflammation and atherogenesis, and the evidence is growing for the role of an
      active inflammation in the atherosclerosis in the coronary circulation and
      elsewhere. Although the seroepidemiological and eradication studies have
      suggested a causal relationship between Helicobacter pylori (Hp) infection and
      coronary heart disease; the issue is still controversial. The detection of Hp
      specific DNA in atheromatous plaque material from coronary arteries, but more
      important, the reduction in restenosis of coronary vessels after Hp eradication
      could be interpreted as an evidence for the involvement of a Hp infection in the
      progression of CAD induced by a local inflammatory process.

PMID- 17033110
TI  - Frequency of Helicobacter pylori infection in children under 4 years of age.
AB  - The work aimed at establishment of frequency of Helicobacter pylori (Hp)
      infection in children under 4 years of age. One hundred ninety-eight children (6
      month to 4 year) were tested using urea breath test (UBT) with the non
      radioactive isotope (13)C (50 mg of urea). The air was collected before and in
      the 20(th) and 30(th) minute after standard meal. The results of measurements
      (mass spectrometry IRMS) were given as a quotient (13)CO(2)/CO(2) (delta), and a
      positive value was set at delta>3,5%. Parents of tested children were asked to
      fill in a questionnaire on a somatic development, the digestive tract symptoms of
      a child and family members as well as socioeconomic conditions. The data were
      analyzed to establish the risk factors in Hp infection in children. Hp infection
      was found in 18,38% of children. It was not related to child's sex nor age. The
      statistical significance was found in the occurrence of Hp infection among
      children whose family members had infection and among those attending creches or
      kindergartens. Non-radioactive (13)C UBT is very useful and easy method to use in
      epidemiological studies even in youngest children. The course of infection was
      asymptomatic and had no impact on their somatic development. Factors increasing
      the risk of Hp infection were occurrence of Hp among other family members and
      contact with other children in educational facilities.

PMID- 17033112
TI  - Guidelines in the medical treatment of Helicobacter pylori infection.
AB  - Scientific evidence based on controlled clinical research confirm substantial
      benefits resulting from the eradication of H. pylori infection in such
      pathologies of the alimentary tract as: gastric peptic and duodenal ulcer (active
      or confirmed in the future and ulcer disease complications), MALT (Mucosa
      Associated Limphoid Tissue) lymphoma, atrophic gastritis, past stomach resection,
      gastric cancer in the family. The above group of indications is strongly
      recommended for eradicative treatment. During the last several years there have
      been many guidelines made by international and national specialist groups. "Test
      and treat" strategy of undiagnosed dyspepsia treatment is based on possibility to
      carry out non-invasive tests confirming H. pylori infection. First symptoms of
      dyspepsia in people over 45 years of age constitute recommendation for endoscopy,
      as well as symptoms assumed to be "alarming" (loss of weight, anaemia, bloody
      vomiting, tarry stool, dysphagia) regardless of patient age. An individual
      approach to eradication is proposed in gastroesophageal reflux disease, and use
      of non-steroid anti-inflammatory drugs. Antibacterial activity towards H. pylori
      is shown by many antibiotics (amoxicillin, macrolides, tetracyclines) and some
      other chemotherapeutic agents (nitroimidazoles) and bismuth. PPIs are
      recommended, because through increase of pH in stomach they create conditions to
      act for antibiotics. During the stage of first line triple therapy, it is advised
      to apply PPI and two antibacterial medicines at the same time (PPI +
      amoxicillin+metronidazole or clarithromycin). Such therapeutic action ensures
      achievement of eradication of H. pylori infection in 80-90% of cases. In case of
      lack of treatment efficiency in the first-line therapy, 7-14 day treatment may be
      repeated using triple therapies (PPI + 2 antibiotics) substituting the antibiotic
      with the metronidazole or tetracycline, or quadruple therapies (PPI + bismuth
      citrate + 2 antibiotics). Side effects during eradicative treatments occur quite
      rarely (from 15 to 30%).

PMID- 17033111
TI  - Efficacy of Helicobacter pylori eradication taking into account its resistance to
      antibiotics.
AB  - The discovery of Helicobacter pylori (H. pylori) provided a possibility to cure
      effectively patients with peptic ulcers. Recent studies have shown varying
      susceptibility of H. pylori strains to antibiotics and increasing resistance to
      some of the recommended drugs. The purpose of the present study was to evaluate
      the efficacy of the currently recommended eradication schemes and to assess the
      increasing resistance of H. pylori strains to recommended antibiotics.
      Furthermore, the effect of probiotics (Lacidofil) on the efficacy of first-line
      treatment with amoxicillin and clarithromycin was analyzed. The study population
      consisted of 641 patients: 192 received amoxicillin with clarithromycin and
      proton pump inhibitor (PPI), 241 - tetracycline, tinidazole, bismuth and PPI, 53 
      amoxicillin with clarithromycin and PPI supplemented with Lacidofil. The
      efficacy of eradication treatment was evaluated by the (13)C-urease breath test.
      The microbiological examination included 111 samples of H. pylori. The present
      study demonstrated low efficacy of the tetracycline, tinidazole, bismuth and PPI
      scheme i.e. 71.4%, moderate efficacy of the amoxicillin with clarithromycin and
      PPI scheme i.e. 85.9%, whereas the supplementation with Lacidofil significantly
      increased the efficacy of eradication to 94.3%. The microbiological examination
      revealed a relatively high level of primary resistance to clarithromycin (22.2%)
      and a high level to metronidazole (46.7%), with no resistance to amoxicillin.
      However, the most important finding is the high level of secondary resistance to
      clarithromycin and metronidazole (more than 66% in both cases). The present
      findings suggest the need for modification of the recommended eradication
      schemes.

PMID- 17033113
TI  - Helicobacter pylori in liver diseases.
AB  - At the present stage of knowledge, the participation of the Helicobacter bacteria
      in the pathology of liver and the bile tract in humans has not been univocally
      documented. However, apparent are the premises so as to go on performing the
      examinations under discussion since the said participation cannot be excluded. If
      the more direct evidence of the etiologic role of the Helicobacter in the
      pathology of liver were available, it would create the chances for the more
      effective treatment of patients than the case has been so far. Cancer commonly
      derives from the chronic inflammation and infection and in case of hepatocellular
      carcinoma (HCC), may arise either from local liver derived progenitor cells
      (LPCs) or bone marrow originated stem cells (BMSCs) and future studies should
      disclose the role of either type of cells and of inflammatory factors such as
      generated by Helicobacter infection in the liver pathophysiology.

PMID- 17033114
TI  - Indian Academy of Pediatrics and polio eradication in India.

PMID- 17033115
TI  - Hypertonic saline treatment in children with cerebral edema.
AB  - OBJECTIVE: To compare the efficacy and side effects of hypertronic saline and
      mannitol use in cerebral edema. DESIGN: Retrospective study. SETTING: Pediatric
      intensive care unit. SUBJECTS: 67 patients with cerebral edema. METHODS: Patients
      with cerebral edema treated with either mannitol or hypertronic saline (HS)
      (Group II: n = 25), and both mannitol and HS (Group III: n = 20) were evaluated
      retrospectively. Cerebral edema and increased intracranial pressure were based on
      the clinical and/or radiological (CT, MR) findings. When treating with both
      mannitol and HS (Group IIIA), if patients serum osmality was greater than 325
      mosmol/L, mannitol was stopped and patients were treated with only HS (Group
      IIIB). All patients were closely monitored for fever, pulse, blood pressure,
      central venous pressure (CVP), oxygen saturation, volume of fluid intake and
      urine output. Mannitol was given at a dose of 0.25-0.5 g/kg while the hypertonic
      saline was given as 3% saline to maintain the serum-Na within the range of 155
      165 mEq/L. RESULTS: There was no statistically significant difference in terms of
      Glasgow coma scale, age, gender, and etiologic distribution between the groups.
      And also distribution of the other treatments given for cerebral edema is not
      significiant. Mannitol was given for a total dose of 9.3 +/-5.0 (2-16) doses in
      Group I, and 6.5 +/-2.8 (2-10) doses in Group III. Hypertonic saline was infused
      for 4-25 times in Group II. Although there was no statistically significant
      difference in the highest serum Na and osmolarity levels of the groups, duration
      of comatose state and mortality rate were significantly lower in Group II and
      Group III A B. Patients who received only HS were subdivided according to their
      serum Na concentrations into 2 groups as those between 150-160 mEqL and those
      between 160-170 mEqL. The duration of comatose state and mortality was not
      different in patients with serum-Na of 150-160 mEqL and in patients with 160-170
      mEqL in the hypertonic saline receiving patients. Four patients in the group II
      developed hyperchloremic metabolic acidosis and 2 patients in the group I had
      hypotension. As two patients in group II had diabetes insipidus and one patient
      had renal failure in group I, the treatment was terminated. The causes of death
      were septic shock, ventilator associated pneumonia with acute respiratory
      distress syndrome, progressive cerebral edema and cerebral edema with pulmonary
      edema. Multivariate analysis showed that age, gender, cause of cerebral edema,
      electrolyte imbalance, hyperglycemia and hyper-ventilation had no significant
      impact on outcome. CONCLUSION: Hypertonic saline seems to be more effective than
      mannitol in the cerebral edema.

PMID- 17033116
TI  - Efficacy and safety of montelukast as monotherapy in children with mild
      persistent asthma.
AB  - OBJECTIVE: To study the efficacy and tolerability of montelukast as monotherapy
      in the treatment of mild persistent bronchial asthma. DESIGN: Open, non
      comparative, prospective, 12-month study. SETTING: Asthma clinic in urban multi
      speciality trust hospital. METHODS: Children (age 3-11 yrs) with mild persistent
      asthma, not on any prophylactic drugs were enrolled consecutively (from January
      to December 2003) and started on 4 mg (2-4 yrs) or 5mg (<4 yrs) montelukast for a
      period of 12 weeks. Efficacy was assessed by improvements in clinical score, peak
      expiratory flow rates (PEFR), spirometry measurements and reduction in reliever
      drug requirement after 4 and 12 weeks of therapy. Side effects were also judged
      after 12 weeks of therapy. RESULTS: 50 children (mean age 5.41 +/-2.11 years)
      completed the study. There was association with positive family history (92%),
      allergic rhinitis (64%), exercise induced asthma (40%), cough variant asthma
      (24%), seasonal asthma (80%) and high IgE (12%) levels. Clinical scores, viz,
      activity, wheeze and cough, improved effectively from (1.64 +/-0.5253) at
      baseline to (0.7 +/-0.7071) and (1.72 +/-0.701) to (0.92 +/-0.6952) and (1.5 +/
      0.6145) to (0.88 +/-0.8241) respectively after 12 weeks of therapy. Significant
      clinical improvement (p >0.001) was also noted after 4 weeks of therapy. Peak
      expiratory flow rates (done in 19 cases) documented improvement from (120.21 +/
      12.23) at baseline to (135.41 +/-23.34) after 12 weeks. FEV1 / FVC (done in 11
      cases) improved from (71.44 +/-1.35%) to (87.10 +/-8.34%) after 12 weeks. Mean
      improvement in all the parameters demonstrated P value less than >.001. A total
      of 19 of 50 cases showed mild side-effects as anorexia (16%), elevated liver
      function tests (18%) and headache (10%). CONCLUSION: The clinical outcome showed
      significant improvement (p < 0.01) after 4 and 12 weeks.

PMID- 17033117
TI  - Epilepsy, antiepileptic drugs and educational problems.
AB  - Epilepsy is a chronic disorder that significantly affects learning and behavior.
      Children with epilepsy are particularly vulnerable to educational problems and
      resultant academic underachievement. Co-morbidities like cognitive and behavioral
      problems contribute significantly for the problems at school. Both epilepsy and
      neuropsychological deficits may occur as different clinical manifestations of a
      common etiological process. Ongoing seizures themselves adversely affect the
      developing brain. Furthermore, psychosocial issues also contribute significantly
      to the problems at school. The effect of antiepileptic drugs is double edged in
      this setting. They may reduce the seizure burden and thus improve the cognitive
      function. However, these drugs also significantly affect the learning process.
      The treating pediatrician should be equipped to comprehensively address all these
      factors for an optimal outcome. Recent onset of educational problems in a child
      with epilepsy deserves immediate and aggressive evaluation and management.

PMID- 17033118
TI  - The recurring coma epidemic in children in India: what is it?

PMID- 17033119
TI  - Clinical profile and morbidity pattern of infants born to HIV infected mothers in
      Durban South Africa.
AB  - This study describes the clinical characteristics and co-infections in infants
      born to HIV infected women being followed up in a high risk clinic of South
      Africa Sixty three percent (302 out of 476) of mothers attended clinic for
      varying periods during follow-up. Sixty four per cent of babies had physical
      clinical signs suggestive of HIV infection. In the majority of babies, persistent
      signs resolved by 9 months of age. In those with persistent signs, 20 percent
      tested positive for HIV infection. Among the HIV exposed infants, co-infections
      with TB, CMV, syphilis and Herpes zoster were diagnosed which appeared
      independent of their ultimate seroconversion status.

PMID- 17033120
TI  - Serum zinc levels in newborns with neural tube defects.
AB  - Neural tube defects (NTD) comprise of a group of congenital malformations that
      include spina bifida, anencephaly and encephalocele. Reports have implicated zinc
      deficiency as one of the causative factors of NTDs. We compared the serum zinc
      level of 23 newborns having neural tube defects with 35 healthy controls by
      spectrophotometery during 2003-2004. Zinc deficiency was documented in 43.5% of
      the cases and 8.6% of the controls (P = 0.002). Multivariate logistic regression
      analysis revealed a significant association between the presence of NTDs and zinc
      deficiency (OR = 8.2, 95% Cl: 1.9-34.7).

PMID- 17033121
TI  - Detection of parvovirus B19 in a case of erythema infectiosum with myositis.
AB  - A well documented case of erythema infectiosum is being reported here for the
      first time from India which was associated with myositis that has not been
      reported globally. A 9-year-old child presented with moderate to high grade
      fever, mild anemia, and erythematous rash involving face, trunks and limbs
      associated with arthralgia, myalgia and myositis. Parvovirus B19 infection was
      confirmed by detection of IgM antibodies (inhouse ELISA) and DNA (nested PCR) in
      patient's serum.

PMID- 17033122
TI  - Isolated left lung aplasia with bronchial asthma.
AB  - Congenital lung anomalies are categorised as pulmonary agenesis, aplasia and
      hypoplasia with distinct clinical implications. An 8-year-old boy was referred
      for an opaque left hemithorax for which he had received antituberculous therapy.
      A detailed evaluation including flowing contrast computed tomography of the
      thorax and fiberoptic bronchoscopy led to a diagnosis of left lung aplasia. He
      also had wheezing dyspnea, which was confirmed as bronchial asthma. Congenital
      lung defects with associated asthma was reported only twice till date. A high
      index of suspicion is required to recognise such a patient.

PMID- 17033123
TI  - Multiple familial trichoepitheliomas.

PMID- 17033124
TI  - Management of traumatic hemobilia with embolization.

PMID- 17033125
TI  - Non-albicans Candida in neonatal candidemia.

PMID- 17033126
TI  - Intravenous breast milk administration--a rare accident.

PMID- 17033127
TI  - Post concussion ataxia following minor head injury.

PMID- 17033128
TI  - Procedural sedation and analgesia by non-anesthesiologists.

PMID- 17033130
TI  - Role of experimental and epidemiological evidence of carcinogenicity in the
      primary prevention of cancer.
AB  - Experimental chemical carcinogenesis, which included long-term tests in
      experimental animals,had a dominating role in cancer research between the 1920s
      and the late 1960s. Two events marked a certain decline of confidence in the
      ability of experimental results to predict human risks: the incapacity of
      developing methods to identify agents acting on the different steps of the
      carcinogenesis process, and the incapacity to reproduce experimentally the strong
      evidence of carcinogenicity of tobacco smoke provided by epidemiological studies.
      It was at that time that epidemiologists and biostatisticians developed criteria
      for assessing the causation of chronic-degenerative diseases relying primarily on
      epidemiological evidence. In 1969 the International Agency for Research on Cancer
      (IARC) did initiate a programme for identifying the cause of cancer with the aim
      of promoting the primary prevention of cancer. The programme is focused on the
      evaluation of the carcinogenicity of environmental agents on the basis of both
      the experimental and epidemiological evidence and, since the 1990s, a balanced
      use of the new tools provided by advances in toxicology, molecular biology and
      genetics. A strong point of the IARC programme is that in the absence of adequate
      human data it is reasonable and prudent to regard agents for which there is
      sufficient experimental evidence of carcinogenicity as if they were carcinogenic
      to humans.

PMID- 17033131
TI  - Structure-activity models of chemical carcinogens: state of the art, and new
      directions.
AB  - Chemical carcinogenicity has been the target of numerous attempts to create
      predictive models alternative to the animal ones, ranging from short-term
      biological assays (e.g. mutagenicity tests) to theoretical models. Among the
      theoretical models, the application of the science of structure-activity
      relationships (SAR) has earned special prominence. The qualitative approach to
      SAR has lead to the identification of a large number of reactive chemical
      substructures that are both mutagenic and carcinogenic. More sophisticated
      developments are the quantitative structure-activity relationship (QSAR) models,
      that link the physical chemical or structural properties of the molecules to the
      toxicological endpoints. Both approaches provide strong support to the process of
      risk assessment of the chemicals, especially in the phase of priority setting.
      Among the areas potentially able to contribute to further developments of (Q)SAR,
      the novel chemical relational databases are presented and discussed. The freely
      downloadable ISSCAN database on chemical carcinogens is presented.

PMID- 17033132
TI  - Towards a harmonized approach for risk assessment of genotoxic carcinogens in the
      European Union.
AB  - The EU Scientific Committees have considered in the past the use of matematical
      models for human cancer risk estimation not adequately supported by the available
      scientific knowledge. Therefore, the advice given to risk managers was to reduce
      the exposure as far as possible, following the as low as reasonably achievable
      (ALARA) principle. However, ALARA does not allow to set priorities for risk
      management, as it does not take into consideration carcinogenic potency and level
      of human exposure. For this reason the European Food Safety Authority (EFSA) has
      identified as a priority task the development of a transparent, scientically
      justifiable and harmonized approach for risk assessment of genotoxic carcinogens.
      This approach, proposed at the end of 2005, is based on the definition of the
      (MOE), i.e. the relationship between a given point of the dose reponse curve in
      the animal and human exposure. As point of comparison EFSA recommends the BMDL10,
      i.e. the lower limit of the confidence interval of the Benchmark Dose associated
      with an incidence of 10% of induced tumors. Based on current scientific
      knowkedge, EFSA concluded that a MOE of 10000 or greater is associated with a low
      risk and low priority for risk management actions. The approach proposed does not
      replace the ALARA. It should find application on food contaminants, process by
      product, and other substances unintentionally present in food. On the other hand,
      it is not intended to provide a tool for the definition of tolerable intake
      levels for genotoxic carcinogens deliberately added to food.

PMID- 17033133
TI  - Development of carcinogenicity classifications and evaluations: the case of
      formaldehyde.
AB  - In this paper carcinogenicity classification and evaluations case of formaldehyde
      made by national and international agencies and organizations (such as European
      Union, International Agency for Research on Cancer, World Health Organization)
      both in occupational (such as American Conference of Government Industrial
      Hygienists, National Institute of Occupational Safety and Health and Occupational
      Health and Safety Administration) and non occupational environment (such as
      United States Environmental Protection Agency) are proposed. The differences in
      the database and consequently in the conclusion are described in a short
      historical review since formaldehyde was considered for the first time as regard
      as health effects.

PMID- 17033134
TI  - Genotoxicity and carcinogenicity of acrylamide: a critical review.
AB  - In 2002, public health concerns were raised by Swedish studies showing that
      relatively high levels of acrylamide were formed during the frying, roasting, or
      baking of a variety of foods, including potatoes, cereal products and coffee at
      temperatures above 120 degrees C. Acrylamide possesses a range of hazardous
      properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity
      and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in
      animals, in which it causes increased tumour incidence at a variety of sites.
      Although the mechanisms for tumour induction in experimental animals have not yet
      fully elucidated, the in vivo genotoxicity at gene and chromosome level in
      somatic and germ cells in rodents cannot be discounted from contributing to it.
      At this time, there is no information to indicate any significant difference
      between rodents and humans in sensitivity to cancer formation from acrylamide.
      The present available epidemiological studies of human industrial and accidental
      exposures have to be considered not suitable for use in the cancer risk
      assessment of acrylamide in food, due to several limitations. In reviewing the
      genotoxicity and carcinogenicity of acrylamide, the author has taken into account
      also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the
      European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint
      FAO/WHO Expert Committee on Food Additive (JECFA) in 2005.

PMID- 17033135
TI  - Mortality study of employees in a factory of recovery and refining of catalytic
      converters in Rome, Italy.
AB  - The study objective is to describe cause specific mortality of employees in a
      plant engaged in production, recovery and refining of catalytic converters
      located in Rome. Previous epidemiological studies conducted in similar plants are
      not available. A total of 828 workers (642 males and 186 females) were followed
      up between 1956 and 31-12-2003. Cause specific standardized mortality ratio (SMR)
      and 90% confidence intervals (CI) were computed using regional rates for
      comparison. Among males hired between 1956 and 1993, followed up until
      31/12/2003, mortality for all causes (SMR 0,8; 90% CI 0,7-1,0; 85 observed) and
      all neoplasms (SMR 0,6; 90% CI 0,42-0,87; 20 observed) is below expected; an
      increase is present for liver cirrhosis (SMR 2,74; 90% CI 1,47-5,1; 7 observed)
      and brain cancer (SMR 5,24; 90% CI 2,3-11,90; 4 observed). The present
      investigation complies with the proposed scientific standards for occupational
      cohort studies. The study was not prompted by well defined a priori hypotheses
      but it is included in a process intended to typify a potentially polluted site;
      the absence of a priori hypotheses and of previous epidemiological evidence,
      prevent from a causal interpretation of the increased mortality from liver
      cirrhosis and brain cancer. The implementation of cohort studies in industrial
      sites where industrial activities similar to the one here examined are present,
      are highly recommended.

PMID- 17033136
TI  - Molecular mechanisms of carcinogenesis by vinyl chloride.
AB  - In 1974 vinyl chloride (VC), a gas used in the plastics industry, was shown to be
      a human carcinogen, inducing a very rare type of tumor, angiosarcoma of the
      liver. The same type of tumor was induced in rodents exposed to VC thus providing
      an excellent model for mechanistic studies. Here, we review the numerous studies
      on the mechanism of action of VC with particular emphasis on the DNA products
      induced by this strong alkylating agent. In particular, the genotoxicity, repair
      mechanisms, in vivo formation and tumor mutation spectra by etheno-adducts will
      be analysed and possible approaches for future research suggested.

PMID- 17033137
TI  - Tamoxifen (TAM): the dispute goes on.
AB  - Tamoxifen (TAM) has been used since early '70s as antitumor agent in the adjuvant
      therapy of breast carcinoma. The aim was (and is) to reduce the incidence of
      contralateral breast cancer in primary breast cancer bearing patients. Its
      efficacy was about 30% when estrogen and progesterone receptors were present in
      the malignant breast tumor and its use in antitumor therapy is, at the present
      time, rather correct. Viceversa, the employment of TAM in chemoprevention of
      breast tumor in healthy and/or at-risk women by more than a decade has been
      contrasting by many scientists and supporting by others. Indeed, TAM produces not
      only beneficial effects but also detrimental effects (mainly induction of
      endometrial cancer). According to the Author of this manuscript, TAM would not be
      used for primary or secondary mammary tumor chemoprevention. For such purposes
      the right way is to wait for conclusion of ongoing clinical trials on other pure
      antiestrogenic agents. Indeed, good candidates to act as an antiestrogen both in
      breast and in endometrial tissue are under validation. In the meanwhile, the
      scientific dispute goes on.

PMID- 17033138
TI  - Additional features of the worldwide double standards in the prevention of
      asbestos-related diseases.
AB  - A search has been made through Pubmed-Medline in order to quantify the production
      of epidemiological studies on the consequences of asbestos in different
      countries. Worldwide, very little epidemiological knowledge on the consequences
      of occupational and environmental exposure to asbestos has been gathered in
      countries known to be the major producers and/or consumers of asbestos. The only
      exception is Canada, which ranks third among asbestos producers and exports most
      of its production. A handful of papers carried out in Brazil are briefly
      commented in order to highlight the difficulties that epidemiological
      investigations face in developing countries.

PMID- 17033139
TI  - Some non neoplastic effects of ELF magnetic fields in experimental animals.
AB  - This study has been addressed to the non neoplastic effects observed in
      experimental animals exposed to the ELF magnetic fields exposure, giving
      particular attention to the large and comprehensive data of the two-year NTP
      (National Toxicology Program) studies. The statistical analysis of non neoplastic
      incidences, whenever not presented by the study authors, has been carried out in
      the present study. Only the effects coherently emerging for both the animal
      genders have been considered; gender specific effects have obviously been
      separately analysed. The trend analysis has been carried out over the 4 exposure
      levels (0, 2, 200 microT, and 1000 microT -microTesla) and on the first 3 ones.
      For 28 dose-response relationships, non neoplastic effects significantly emerged
      (6 for hyperplasia, 4 for cyst, 4 for inflammation, 3 for focus, 3 for atrophy, 2
      for cellular infiltration, and 1 for each of other 6 effects). This number is
      much higher than the one of neoplastic effects indicated by the NTP as
      significant. For many of these dose-response relationships, the trend was
      significant only over the first 3 treatment levels (excluding the highest one,
      1000 microT/1 mT), in agreement with the results of some other studies indicating
      a response reduction, or even a possible anticarcinogenic effects, at
      considerably high exposures (mT range). The obtained results suggest a complex
      effect modulation pattern.

PMID- 17033140
TI  - Carcinogen-modified DNA and specific humoral immunity toward carcinogen-DNA
      adducts. A review.
AB  - Carcinogenesis is a complex and multistep process starting from initiation to
      tumor progression. Damage to DNA, induced by the covalent binding of chemical
      carcinogens on critical DNA segments, reflects exposure and is directly related
      to tumor formation. For this reason it's very important detect and quantify DNA
      adducts by using highly sensitive methods. During the last 30 years sophisticated
      methods have been developed, in particular immunoassays that have a widespread
      application in monitoring animal models and human tissues for evidence of
      carcinogen exposure. In this paper we describe the work done in our laboratory,
      from the production of antibodies specific for two different carcinogens, 2
      Acetylaminofluorene and Benzo[a]pyrene, to their application in chemical
      carcinogenesis studies. Moreover, we describe as immunological methods can be
      used for detecting the presence of specific antibodies in sera of exposed
      individuals.

PMID- 17033141
TI  - [The HIV/AIDS epidemic in the Province of Sassari in the combination
      antiretroviral therapy era].
AB  - Combined antiretroviral therapy has reduced both AIDS mortality and morbidity. An
      unknown proportion of patients is identified early and starts therapy before
      developing AIDS, thus escaping epidemiological surveillance. For this reason it
      is important to monitor the trend of new diagnoses of HIV infection. From the
      comparison of patients living in the Province of Sassari with new diagnoses of
      HIV infection or AIDS in the period 1997-2003 some differences emerge. Males are
      the most affected, but the difference tends to decrease among new HIV cases.
      Sexual contact is the most common route of transmission among new HIV diagnoses,
      whereas the parenteral route prevails among AIDS cases. An increase in the
      percentage of foreigners has been found only among new HIV cases. The difference
      found between new AIDS and HIV cases emphasises the importance to implement HIV
      infection based surveillance systems, in order to better guide informative
      campaigns and other interventions.

PMID- 17033142
TI  - [Molecular epidemiology of imported malaria in Italy: the use of genetic markers
      and in vitro sensitivity test in a study of chloroquine resistance in Plasmodium
      falciparum].
AB  - The emergence of Plasmodium falciparum drug-resistance, especially chloroquine
      resistance, represents one of the main obstacles to the control of malaria.
      Several studies have shown that in P. falciparum the mechanism of chloroquine
      resistance is linked to specific point mutations in the pfcrt gene of the
      parasite. In the present study we have analyzed 120 Italian imported malaria
      cases to evaluate the prevalence of 76T and 220S mutantions in the pfcrt gene.
      Moreover, the correlation between the presence of pfcrt point mutations and in
      vitro chloroquine resistance has been evaluated on 25 plasmodial isolates. The
      results showed a high prevalence of the pfcrt point mutations in isolates
      analyzed and a significant association between point mutations and in vitro
      chloroquine resistance. Molecular screening on imported malaria cases can be a
      useful tool to be employed in surveillance activity and also in monitoring the
      development and spread of drug resistance in endemic areas.

PMID- 17033143
TI  - [DNA-microarray: new technological approaches on twin studies].
AB  - The completion of the Human Genome Project, and the innovations introduced in
      biotechnology are changing how to study twins. Here, we summarize some molecular
      studies performed on populations of discordant monozygotic twins (MZ) applying
      microarrays. Microarrays are an orderly arrangement of high numbers of probes
      (DNA, RNA or proteins), immobilized onto a matrix. The microarray approach allows
      a global analysis of gene expression, and therefore might point out the molecular
      mechanisms of MZ twins' discordance, such as epigenetic mechanisms. The
      application of microarray to twin studies will help better define, through
      bioinformatics, the role of genes and environment in the development of human
      diseases, thus suggesting new diagnostic and therapeutic approaches.

PMID- 17033144
TI  - Animal welfare and protection during transport: the current legislative framework
      in European Union.
AB  - The Protocol on the protection and welfare of animals annexed to the Amsterdam
      Treaty (1997) establishing the European Community requires that in formulating
      and implementing agriculture and transport policies, the Community and the Member
      States shall pay full regard to the welfare requirements of animals. In the field
      of animal welfare, transport has been, and still is today, cause of much
      controversy. Council Directive 91/628/EEC, amended by Directive 95/29/EC,
      constitutes the current Community legislative framework. In the light of
      experience gained under Directive 91/628/EEC at harmonising Community legislation
      on the transport of animals, and the difficulties encountered due to the diverse
      transposition of that Directive at national level, it was more appropriate to set
      out Community rules in this field in a regulation. In fact Council Regulations
      (EC) no. 97/1255, no 98/411 and no. 2005/1 were adopted subsequently to provide
      more detailed rules. This paper is aimed to review the current EU legislation
      affecting the animal transport.

PMID- 17033145
TI  - [ADHD and multimodal intervention].
AB  - During the year 2003, the National Register of the Attention deficit
      hyperactivity disorder (ADHD) has been implemented in Italy. It was commissioned
      by the Ministry of Health to the Istituto Superiore di Sanita, which is its
      leading technical and scientific body, with the aim to set up a sound database
      gathering detailed information on the prescription of Ritalin at the national
      level. The latter represents the most diffused elective drug treatment for such
      an early-onset neuropsychiatric syndrome. To this aim, the more prevalent
      theories on the pathogenesis of ADHD and the debate on therapy are reviewed and
      discussed. This paper is aimed at emphasizing that this kind of systematic data
      gathering of such a Register has not to be meant an unconditional approval of a
      therapeutical approach based on drug therapy only. Pharmacological therapies may
      or may not be included within the frame of a multimodal complex treatment plan
      which should also rely on psychological intervention.

PMID- 17033146
TI  - Evidence-based medicine for neurosurgeons: introduction and methodology.
AB  - Evidence-based medicine is a tool of considerable value for medicine and
      neurosurgery that provides a secure base for clinical practice and practice
      improvement, but is not without inherent drawbacks, weaknesses and limitations.
      EBM finds answers to only those questions open to its techniques, and the best
      available evidence can be a far cry from scientific truth. With the support and
      backing of governmental agencies, professional medical societies, the AAMC, the
      ACGME, and the ABMS, EBM is likely here to stay. The fact that: (1) EBM
      philosophy and critical appraisal techniques have become fully integrated into
      the training and culture of our younger colleagues, (2) that maintenance of
      certification will require individuals to demonstrate personal evidence based
      practice based on tracking and critical analysis of personal practice outcomes as
      part of the performance-based learning and improvement competency, and (3) that
      the progressively growing national healthcare expenditures will necessitate
      increasing basis of reimbursement and funding based on evidence-based
      effectiveness and guidelines, all point to the likelihood that complete immersion
      of neurosurgical practice in EBM is inevitable. This article thoroughly explores
      the history of EBM in medicine in general and in neurosurgery in particular.
      Emphasis is placed on identifying the legislative and regulatory motive forces at
      work behind its promulgation and the role that organized medicine has taken to
      facilitate and foster its acceptance and implementation. An accounting of
      resources open to neurosurgeons, and a detailed description EBM clinical decision
      making methodology is presented. Special emphasis is placed on outlining the
      methodology as well as the limitations of meta-analyses, randomized clinic
      trials, and clinical practice parameter guidelines. Commonly perceived
      objections, as well as substantive problems and limitations of EBM assumptions,
      tools, and approaches both for individual clinical practice and health policy
      design and implementation are explored in detail.

PMID- 17033147
TI  - Evaluation of epidemiologic evidence for primary adult brain tumor risk factors
      using evidence-based medicine.
AB  - We evaluate genetic, behavioral, developmental and experiential risk factors for
      primary adult brain tumors (primarily, astrocytoma and meningioma) using a
      systematic set of principles adapted from evidence-based medicine standards. In
      addition to ionizing radiation, rare mutations in highly penetrant genes
      associated with certain diseases/syndromes, and epilepsy and seizures (which
      probably result from, rather than cause, adult brain tumors), only the
      unexplained observation of familial aggregation of astrocytoma has been
      consistently shown. There is promising renewed interest in associations between
      infections, allergic conditions and adult brain tumor risk. Our knowledge of the
      causes of adult brain tumors is limited and should be expanded by results from
      large, well-designed studies of novel potential risk factors and potential
      interactions between known and suspected risk factors.

PMID- 17033149
TI  - Pediatric neurosurgery.
AB  - Randomized controlled trials of neurosurgical procedures involving children have
      been organized infrequently; as a consequence, the majority of pediatric
      neurosurgical practice is not supported by class I data. Furthermore, many trials
      that have been reported suffer from serious methodological shortcomings such as
      insufficient power and poor statistical analysis. Finally, several trials of
      neurosurgical techniques that are frequently performed on children have either
      excluded children from participation or include an insufficient number of
      children to draw strong conclusions. Despite these shortcomings, pediatric
      neurosurgery, like all fields in medicine, is gradually moving towards a more
      stringent evidence-based medicine standard. This chapter will attempt to
      summarize the recent progress that has been made in this area.

PMID- 17033148
TI  - Benign adult brain tumors: an evidence-based medicine review.
AB  - BACKGROUND: Benign adult brain tumors can be managed conservatively or using
      surgery, radiation, or medicines. While randomized comparisons assessing tumor
      recurrence, quality of life, or survival are the ideal means of comparing
      treatments, it can be difficult to recruit patients to such trials and lengthy
      follow-up periods are needed because of the slowly progressive natural history of
      these tumors. METHODS: Review of the literature on benign adult brain tumors
      using evidence-based standards and focusing on meningiomas, pituitary adenomas,
      and vestibular schwannomas, which together represent the majority of WHO grade 1
      adult brain tumors. RESULTS: Nearly all studies of benign adult brain tumors were
      of relatively poor quality (level 3 or poorer). These studies enable grade C
      recommendations. The safety of meningioma surgery in the elderly varies with
      institution, radiosurgery is a reliable alternative to surgery in small to medium
      sized meningiomas, and the efficacy of drugs in therapy of meningiomas recurring
      after surgery is difficult to interpret due to a lack of uniform criteria in the
      studies. Radiosurgery is effective in nonfunctional pituitary adenomas recurring
      after surgery, while phototherapy is a newer treatment modality with potential
      benefits in pituitary adenomas that fail surgery or radiation. Vestibular
      schwannomas can be conservatively managed, but there are no reliable predictors
      of growth, so serial imaging is important. Radiosurgery has proven to be a
      reliable alternative to surgery for small to medium-sized vestibular schwannomas,
      but followup has been relatively short in most studies to date. CONCLUSIONS:
      While randomized clinical trials comparing conservative management, surgery,
      radiation, and medical management of benign adult benign tumors are unlikely to
      occur, there is some level 3 evidence that can assist in their treatment.

PMID- 17033150
TI  - Cerebrovascular-endovascular.
AB  - This chapter will review the current status of scientific knowledge to support
      evidence-based medicine guidelines for the endovascular treatment of
      cerebrovascular disease. Three major areas of cerebrovascular disease will be
      examined, (1) occlusive cerebrovascular disease, (2) vascular malformations and
      (3) intracranial aneurysms. Levels of evidence vary in each area and the reasons
      for this variation as well as the challenges that may limit further
      investigations are discussed.

PMID- 17033151
TI  - Evidence-based guidelines in lumbar spine surgery.
AB  - Lumbar fusion is a commonly performed procedure for the treatment of painful
      instability of the spine, usually manifest as chronic low back pain. The safety,
      efficacy, and cost of these procedures have been questioned in the professional
      and lay press. Recently, evidence based medicine techniques have been used to
      investigate the role of lumbar fusion for the treatment of a variety of spinal
      disorders. This chapter describes the general principles and procedures used for
      the development of evidence based guidelines for the performance of lumbar
      fusion.

PMID- 17033152
TI  - Spine: minimally invasive techniques.
AB  - Minimally invasive spine surgery decompression, arthrodesis, and instrumentation
      techniques are now being applied in a wide variety of percutaneous, laparoscopic
      and minimal access procedures. There is currently little longitudinal long-term
      data on these procedures to document their efficacy, indications, limitations or
      complications as compared to standard open techniques. Further complicating such
      direct comparisons is that widely used spine outcomes instruments often do not
      capture the relative benefits of these new procedures. It is only through
      randomized trials that the potential benefits of these procedures be
      substantiated in order to justify the sometimes significant increased costs
      associated with them.

PMID- 17033153
TI  - An evidence-based medicine review of stereotactic radiosurgery.
AB  - BACKGROUND: Stereotactic radiosurgery has been increasingly utilized to manage a
      wide variety of indications including vascular malformations, benign and
      malignant tumors, and functional disorders. METHODS: Review of the recent
      literature on stereotactic radiosurgery by evidence-based standards. RESULTS: The
      vast majority of published papers on stereotactic radiosurgery is of rather poor
      quality (level 3 or below). Two studies provide level 1 evidence showing an
      improvement in local tumor control or survival for patients with 1-3 brain
      metastases having radiosurgery in conjunction with whole brain radiation therapy
      when compared to patients having whole brain radiation therapy alone. One
      randomized trial found no improvement in facial pain outcomes for trigeminal
      neuralgia patients having a longer segment of the nerve irradiated. CONCLUSION:
      For a variety of reasons it is unlikely that randomized clinical trials will be
      performed to evaluate the clinical usefulness of stereotactic radiosurgery.
      Nonetheless, the preponderance of level 3 information supports the role of
      radiosurgery as either an adjunct or alternative to surgical resection or
      fractionated radiation therapy.

PMID- 17033154
TI  - Evidenced-based guidelines for traumatic brain injuries.
AB  - An enormous amount of clinical and basic science brain injury research has been
      undertaken during the last several decades in an effort to improve outcomes
      following severe traumatic brain injury, but to date there still are no new
      therapies that have been clearly shown to be beneficial. There is, however,
      increasing evidence to suggest that evidence-based, protocol-driven, acute care
      can lead to improved outcomes. Evidence based guidelines for the medical and
      surgical management of severe brain injury, and for penetrating and pediatric
      brain injury, as well as for the pre-hospital management of brain injury, have
      all been published. In this chapter the conclusions of those guidelines is
      reviewed. In addition, the studies that demonstrate improved outcomes as a result
      of implementation of the guidelines are summarized.

PMID- 17033155
TI  - Treatment of chronic pain with neurostimulation.
AB  - Chronic pain conditions are a complex and multifactorial problem generally
      requiring a multidisciplinary-type approach. The central nervous system at some
      point clearly becomes involved in the processing of these painful conditions with
      an integration of complex changes in neurophysiology and behavior. Many ablative
      techniques have been employed in the past to interrupt these signals. However,
      the results were often temporary and symptoms tended to recur. The more modern
      approach has suggested that modulation of the nervous elements may be a more
      resilient approach for treating such chronic pain disorders. We are realizing
      that many of these pain conditions are also dynamic and evolving, and as such
      need a similar treatment modality. Neurostimulation, thus, provides the ability
      of therapeutically dosing electrical current in a variety of pulse forms,
      amplitudes, pulse widths, and frequencies, to affect that system. Furthermore, it
      is not destructive, it is reversible, and it can be remotely adjusted and
      programmed over time; clear advantages to previous surgical therapies. This
      chapter reports on the current evidence for the use of neurostimulation (i.e.
      spinal cord stimulation, motor cortex stimulation and deep brain stimulation) in
      the treatment of chronic pain conditions.

PMID- 17033156
TI  - Academic skills: I got my own laboratory! And now what?

PMID- 17033158
TI  - Effects of p-nonylphenol and 4-tert-octylphenol on the anterior pituitary
      functions in adult ovariectomized rats.
AB  - p-Nonylphenol (NP) and 4-tert-octylphenol (OP) are known to mimic the action of
      estrogens as endocrine disruptors. However, their acute effects on the pituitary
      and the hypothalamus functions in vivo have been uncertain. We therefore
      determined their effects on the anterior pituitary, in particular, gonadotropin
      secretion. Two weeks after ovariectomy, the rats were given a subcutaneous
      injection of 10 mg NP, 10 mg OP, 10 mg bisphenol A, 1 microg 17beta-estradiol, or
      sesame oil alone as control. Twenty-four hours after the treatment, the
      expression of progesterone receptor mRNA in the anterior pituitary and the level
      of luteinizing hormone (LH), follicle-stimulating hormone, and prolactin were
      determined. The expression of progesterone receptor mRNA in the anterior
      pituitary was significantly increased by either NP, OP, bisphenol A, or
      estradiol, but bisphenol A was less effective. The level of LH was significantly
      decreased by either NP or OP, but not by bisphenol A and estradiol. Only
      estradiol significantly increased the level of prolactin. The level of follicle
      stimulating hormone was unchanged by any of the treatments. To check the effects
      of NP and OP on pulsatile LH secretion, blood samplings were done at 6-min
      intervals for 3 h. Twenty-four hours after treatment in ovariectomized adult
      rats, we found that the injection of NP significantly decreased the amplitude of
      LH pulses and the mean LH concentrations, but not the frequency of LH pulses. The
      injection of OP significantly decreased the mean LH concentrations without
      affecting the frequency and amplitude of the LH pulses. Finally, the rats given
      an injection of NP or sesame oil were intravenously injected with 50 ng of
      gonadotropin-releasing hormone (GnRH) to check whether NP affected the LH
      secretory responsiveness of the anterior pituitary to GnRH. We found that the
      responsiveness to GnRH in NP-injected rats was significantly attenuated compared
      to the sesame oil-injected rats. The present study suggests that NP, even with a
      single injection, suppresses the pulsatile LH secretion in adult ovariectomized
      rats, probably by affecting the anterior pituitary level.

PMID- 17033159
TI  - Hearing in patients with intracanalicular vestibular schwannomas.
AB  - This paper reports data on the spontaneous course of hearing in 156 patients with
      purely intracanalicular vestibular schwannomas. The mean pure tone average (PTA)
      was 51 dB HL and the mean speech discrimination score (SDS) 60% at diagnosis. The
      risk of a significant subsequent hearing loss (>or=10 dB PTA or >or=10% SDS) was
      54% during 4.6 years of observation. Patients with normal speech discrimination
      at diagnosis had a significantly smaller risk of loosing hearing. The hearing
      loss at diagnosis and during observation was not related to age, gender,
      diagnostic tumor size, tumor- induced expansion of the internal auditory canal or
      tumor sublocalization (fundus, central or porus). However, the loss of PTA was
      smaller in shrinking tumors and the PTA deterioration rate correlated with the
      volumetric tumor growth rate. After 4.6 years observation, the PTA had increased
      by 14 dB to 65 dB HL, and the SDS reduced by 17% to 43%. The proportion of
      patients eligible for hearing preservation treatment as determined by word
      recognition score class I (70-100% SDS) was reduced to 28% (a 44% reduction), and
      by AAO-HNS class A to 9% (a 53% reduction).

PMID- 17033160
TI  - Effect of age and cognition on childhood speech in noise perception abilities.
AB  - This research on children's speech in noise and cognitive abilities aimed to
      determine the age-related trends in speech in noise perception abilities and the
      relationship between speech in noise perception and cognitive abilities.
      Monosyllabic distinguishable (consonant-vowel-consonant) words was the most
      recognisable word category, followed by monosyllabic confusable words (consonant
      vowel-consonant), disyllabic non-words (/aCa/) and monosyllabic syllables (/Ca/),
      demonstrating that phoneme distinctiveness and a reduction in word confusability
      contribute to their recognition. Older children outperformed younger children on
      all speech in noise tasks, indicating that there are age-related trends in speech
      in noise abilities. Children with higher cognitive abilities did not outperform
      children with lower cognitive abilities on speech in noise tasks, indicating that
      the ability to hear speech in noise may be an intrinsic feature of the auditory
      system that matures with age.

PMID- 17033161
TI  - Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic
      deafness from Taiwan.
AB  - Ion channels play important roles in signal transduction and in the regulation of
      the ionic composition of intra- and extracellular fluids. Mutations in ion
      channels have long been thought to be responsible for some forms of hearing loss.
      Defects in KCNQ4, a voltage-gated potassium channel, are a cause of nonsyndromic
      sensorineural deafness type 2, an autosomal dominant form of progressive hearing
      loss. We present data of mutation analysis of KCNQ4 from 185 unrelated Taiwanese
      probands with nonsyndromic hearing loss. The analysis revealed three novel KCNQ4
      mutations and many polymorphisms. The prevalence of KCNQ4 gene mutations in this
      study was 1.62% (3/185). The mutations include a missense mutation (F182L) and
      two silent mutations (R216R and T501T). The F182L missense mutation was located
      in the S3 domain of KCNQ4. The F182 residue of KCNQ4 is highly conserved in KCNQ4
      among various species and is less conserved in all members of the KCNQ family. In
      addition, although R216R is a silent mutation and does not alter the content of
      amino acid residue, the neural network prediction system revealed that it can
      potentially create a novel splice donor site during transcription. This mutation
      might affect the protein structure of KCNQ4 and consequently the normal function
      of the K+ channel. Our data provide the first comprehensive analysis of the KCNQ4
      gene in Taiwanese patients with nonsyndromic deafness.

PMID- 17033162
TI  - Auditory brainstem implantation to rehabilitate profound hearing loss with
      totally ossified cochleae induced by pneumococcal meningitis.
AB  - Hearing rehabilitation by cochlear implantation is not always possible in case of
      total ossification after pneumococcal meningitis. We report 3 cases of
      postmeningitis profound hearing loss with total cochlear ossification in adults
      who underwent auditory brainstem implantation (Nucleus 22, Cochlear Inc., Lane
      Cove, Australia) between 1999 and 2004. The postoperative follow-up period ranged
      from 1 to 6 years. Eleven to 15 out of 22 electrodes were activated. All patients
      had significant speech discrimination in the sound-only mode and an enhanced lip
      reading performance with the implant. Auditory brainstem implants are an
      efficient means of auditory rehabilitation and may be considered in selected
      cases of bilateral profound hearing loss with the impossibility of cochlear
      implantation.

PMID- 17033164
TI  - It's time to distinguish the sign 'creeping eruption' from the syndrome
      'cutaneous larva migrans'.

PMID- 17033163
TI  - Audiological outcome of infants with congenital cytomegalovirus infection in a
      prospective study.
AB  - The aim of this study was to evaluate the audiological outcome of long-term
      follow-up of infants with asymptomatic congenital cytomegalovirus (CMV) infection
      as defined by the presence of CMV DNA in neonatal urine. 12599 pregnant women
      underwent screening for CMV IgG and IgM antibodies between 1996 and 2003.
      Eighteen infants with congenital CMV infection were identified. These infants
      underwent the newborn hearing screening test or auditory brainstem response test.
      Follow-up hearing assessments were performed with the auditory brainstem response
      and behavioral audiometry. The seropositive rate of CMV IgG antibody among the
      pregnant women was 75.3%, and the yearly seropositive rate decreased over the
      study period. One hundred and forty-six pregnant women were positive for IgM
      antibody, and 18 neonates (12.3%) had congenital CMV infection. Sensorineural
      hearing loss (SNHL) was detected in 4 (25%) of the 16 infants with asymptomatic
      infection and 1 (50%) of the 2 infants with symptomatic infection during the
      first 6 months of life. Two infants who passed the newborn hearing screening had
      a delayed-onset SNHL in follow-up examinations up to 4 years of age. Two had
      progressive hearing loss and 2 had improvement of hearing loss. Screening of
      pregnant women for CMV infection and repeated audiological examinations of
      infants are necessary because there are infants with delayed-onset SNHL or
      improved SNHL caused by asymptomatic congenital CMV infection.

PMID- 17033165
TI  - Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further
      cases and current overview.
AB  - The increasing use of anti-TNF-alpha agents led to a better knowledge of their
      side effects. Among the cutaneous reactions, psoriasiform eruptions are
      increasingly described. We encountered 3 further psoriasiform eruptions during
      anti-TNF-alpha treatment for rheumatologic conditions and review the literature
      in order to identify the common characteristics of these cases. We found 30 case
      reports by using a comprehensive search of the 1966-2005 Medline database with a
      wild variety concerning the psoriasis type of eruption, the anti-TNF-alpha agent,
      the treatment duration and the presence or absence of a personal or familial
      history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF
      alpha treatment seems to be a class effect, without any as yet known identified
      predisposing factors, but it is more often self-limited and does not require
      treatment discontinuation.

PMID- 17033166
TI  - Detection of melanoma relapse: first comparative analysis on imaging techniques
      versus S100 protein.
AB  - BACKGROUND: Early detection of melanoma recurrence is essential for the patient's
      prognosis. The serum S100 level may be a useful tool to detect relapse early.
      OBJECTIVE: To compare the efficacy of imaging techniques and serum S100 in the
      early detection of melanoma progression. This is the first report of a comparison
      of a serum marker with an imaging tool in the follow-up of melanoma patients.
      METHODS: From 1992 to 2003, we screened 192 patients suffering from melanoma
      recurrence after a disease-free interval. Of those, 127 patients were identified
      whose S100 levels had been assessed parallel to imaging procedures. RESULTS:
      Serum S100 was elevated in 37% of patients at the time of relapse. In stage III,
      32% of the patients had elevated S100 levels whereas in case of progression to
      stage IV, 48% of the patients presented with increased S100. In 5.5% of patients,
      S100 was the first indicator of disease progression. Imaging procedures lead to
      detection of melanoma recurrence in 26.8%. CONCLUSION: A rising level of serum
      S100 is a specific and sensitive marker of melanoma progression.

PMID- 17033167
TI  - Aberrant DNA methylation silences the novel heat shock protein H11 in melanoma
      but not benign melanocytic lesions.
AB  - BACKGROUND: The heat shock protein H11 is silenced in melanoma cell lines, where
      its forced expression by demethylation with Aza-C triggers apoptosis. OBJECTIVE:
      To examine whether H11 is silenced by aberrant DNA methylation in melanoma as
      compared to nevi and normal skin tissues. METHODS: Cell suspensions from benign
      intradermal nevi, atypical nevi and malignant melanoma tissues were used in
      reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues
      were stained with H11 antibody. RESULTS: H11 is methylated in 60-75% of melanoma
      and atypical nevi, but not in normal skin or most benign nevi. Methylation is
      inversely correlated with H11 expression. CONCLUSION: The heat shock protein H11
      is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic
      lesions or normal skin melanocytes. The data suggest that H11 is a promising
      target for the molecular therapy of melanoma.

PMID- 17033168
TI  - A new mutation of the double-stranded RNA-specific adenosine deaminase gene in a
      family with dyschromatosis symmetrica hereditaria.
AB  - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary
      genodermatosis characterized by a mixture of hyperpigmented and hypopigmented
      macules localized on the back of the extremities and caused by mutations in the
      double-stranded RNA-specific adenosine deaminase (DSRAD) gene. OBJECTIVE: To
      identify gene mutations of DSRAD in patients with DSH. METHODS: A Chinese
      pedigree of typical DSH was subjected to mutation detection in DSRAD. Direct
      sequencing of all PCR products of the whole coding regions of DSRAD was performed
      to identify the mutation. RESULTS: A missense mutation 2747G-->T in the DSRAD
      gene was found in the affected members but not in the healthy individuals in this
      family and in 50 unrelated controls. CONCLUSION: Our study found a novel missense
      mutation in exon 9 of the DSRAD gene. We add new variants to the knowledge of
      DSRAD mutations in DSH.

PMID- 17033169
TI  - A review of malignancies observed during efalizumab (Raptiva) clinical trials for
      plaque psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic, incurable immune-mediated disease. Most
      therapies used for moderate to severe psoriasis are immunosuppressive. Agents
      that depress immune function, including traditional psoriasis therapies, have
      been associated with an increased incidence of malignancies. Efalizumab is a
      recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in
      psoriasis patients. OBJECTIVES: To evaluate the incidence of malignancy in
      patients receiving efalizumab during clinical trials compared with placebo
      treated patients, psoriasis patients from external cohorts and the general US
      population. METHODS: Patient data were pooled from multiple phase III placebo
      controlled, open-label efalizumab clinical trials, and the incidence rate of
      reported malignancies was calculated as a function of patient years of
      observation. The results for the efalizumab-treated patients were compared with
      the data on psoriasis patients from insurance claims databases and a registry of
      events in the general population. RESULTS: The efalizumab- and placebo-treated
      patients had similar incidence rates of malignancy, including lymphoproliferative
      disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The
      incidence of nonmelanoma skin cancers, including basal cell carcinoma and
      squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated
      relative to the external databases. CONCLUSIONS: These results suggest that
      efalizumab treatment does not increase a patient's risk for malignancy. The
      difference observed with nonmelanoma skin cancer may be due to biases introduced
      by the clinical trial methodology. Additional patient observation is necessary to
      ascertain whether a link exists between efalizumab therapy and nonmelanoma skin
      cancer above that normally observed in psoriasis patients.

PMID- 17033170
TI  - Tumescent suction curettage in the treatment of axillary hyperhidrosis:
      experience in 63 patients.
AB  - BACKGROUND: Axillary hyperhidrosis is a common and most distressing problem,
      which can be addressed by a variety of treatment modalities. OBJECTIVE: To assess
      the value of tumescent suction curettage in the treatment of axillary
      hyperhidrosis. METHODS: 63 patients (39 female, 25 male; mean age 30.3 +/- 7.6
      years) with axillary hyperhidrosis were enrolled in the study. All patients were
      treated in an outpatient setting with tumescent suction curettage of the axillary
      cavity, using two entry sites. The results were evaluated with the iodine-starch
      test after 4 weeks and after 6 months. Two years after the procedure, patient
      satisfaction was evaluated as 'satisfied', 'partially satisfied' or
      'dissatisfied'. RESULTS: None of the patients had early postoperative
      complications of infection or seroma. All patients had a marked reduction of
      hyperhidrosis after 4 weeks, confirmed by the iodine-starch test. After 6 months,
      15 patients had high sweat rates and asked for repeat surgery. Two years after
      the procedure, 49 patients were satisfied, 11 patients were partially satisfied
      and 3 patients were dissatisfied. CONCLUSION: Tumescent suction curettage is a
      safe and effective treatment of axillary hyperhidrosis resulting in a high level
      of patient satisfaction. Some patients will need repeat surgery. Suction
      curettage, however, should not be used as the first line of treatment in axillary
      hyperhidrosis.

PMID- 17033171
TI  - Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of
      condylomata acuminata.
AB  - BACKGROUND: Genital warts are a common sexually transmitted disease caused by
      human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self
      administration, has been used most extensively in the treatment of genital warts.
      Imiquimod, a novel immune response modifier capable of inducing interferon-alpha
      and a variety of cytokines, has been examined as a potential treatment for
      genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared
      in any extensive and formal studies, although they are the common topical agents
      for genital warts. OBJECTIVE: To evaluate the efficacy and safety of topical 5%
      imiquimod and 0.5% podophyllotoxin in the treatment of genital warts. METHODS: We
      searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane
      Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5%
      imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were
      collected. Two reviewers extracted the data and independently assessed the
      quality of the included medical literature. Then, meta-analysis was conducted.
      RESULTS: Twelve studies including 3 placebo-controlled trials of imiquimod and 9
      placebo-controlled trials of podophyllotoxin were included. The clinical cure
      rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively,
      without statistically significant differences between the two (p > 0.05). A
      combined analysis of the 3 studies on imiquimod showed a statistically
      significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95%
      confidence interval (CI) 6.05-22.44], as did a combined analysis of the 9 studies
      on podophyllotoxin (pooled OR 16.70, 95% CI 7.06-39.48). The most common adverse
      events of imiquimod were erythema, erosion, excoriation, itching and burning;
      those of podophyllotoxin were burning, pain, erosion, itching and inflammation.
      CONCLUSION: Imiquimod and podophyllotoxin possess similar curative effects on
      condylomata acuminata but podophyllotoxin has more serious adverse effects.

PMID- 17033172
TI  - Evaluation of the antibacterial activity of a special silk textile in the
      treatment of atopic dermatitis.
AB  - BACKGROUND: Increased skin Staphylococcus aureus colonization is frequently found
      in atopic patients. The reduction of local overinfection decreases skin
      inflammation and improves the flares. OBJECTIVE: To evaluate the effectiveness of
      the antimicrobial activity of a silk fabric (MICROAIR DermaSilk) coated with
      alkoxysilane quaternary ammonium with durable antimicrobial properties (AEGIS AEM
      5572/5) in children affected by atopic dermatitis (AD). METHODS: Sixteen
      children, 12 affected by AD with symmetric eczematous lesions on the antecubital
      areas and 4 without any cutaneous disease, used, for 7 days, tubular arm covers
      made of this special silk fabric but only one of each pair was coated with AEGIS
      AEM 5572/5. Microbiological examinations were done with standard cultural swabs
      and by means of quantification of bacterial agents using agar plates at baseline,
      after 1 h and after 7 days. RESULTS: After 7 days a significant improvement in
      the mean value of the 'local SCORAD' index was observed in both the covered areas
      compared to the values obtained at baseline. The reduction in the mean number of
      colony forming units per square centimetre was similar in both areas.
      CONCLUSIONS: Although this special silk fabric seems to be able to improve skin
      lesions in AD, we were unable to demonstrate that such silk fabrics coated with
      AEGIS AEM 5572/5 have an antibacterial activity in vivo, as shown in vitro.

PMID- 17033173
TI  - Antimicrobial silk clothing in the treatment of atopic dermatitis proves
      comparable to topical corticosteroid treatment.
AB  - BACKGROUND: Atopic dermatitis (AD) is aggravated by mechanical irritation and
      bacterial colonization. OBJECTIVE: This study compared the efficacy of an
      antimicrobial silk fabric (DermaSilk) with that of a topical corticosteroid in
      the treatment of AD. METHODS: Fifteen children were enrolled and wore a dress,
      where the left side was made of DermaSilk and the right side was made of cotton.
      The right arm and leg were treated daily with the corticosteroid mometasone for 7
      days. The treatment efficacy was measured with a modified EASI (Eczema Area and
      Severity Index) and with an assessment by the patients/parents and by a
      physician. All patients were evaluated at baseline, as well as 7 and 21 days
      after the initial examination. RESULTS: All parameters showed that, irrespective
      of the treatment, there was a significant decrease of eczema after 7 days. No
      significant difference between DermaSilk-treated and corticosteroid-treated skin
      could be observed. CONCLUSION: DermaSilk showed potential to become an effective
      treatment of AD.

PMID- 17033174
TI  - A case of vulvar pyoderma gangrenosum associated with collagenous colitis.
AB  - Pyoderma gangrenosum is a reactive inflammatory dermatosis which belongs to the
      spectrum of neutrophilic dermatoses. Due to a lack of diagnostic criteria,
      pyoderma gangrenosum is mainly a diagnosis of exclusion. It is rarely observed on
      the perineum, and vulvar involvement is even less frequent. Collagenous colitis
      is an idiopathic inflammatory colonic disease that is included in the microscopic
      colitides. The colonic mucosa and the crypt architecture are preserved but
      histologic alterations are found. We describe a case of collagenous colitis
      associated with vulvar pyoderma gangrenosum that improved spectacularly with
      cyclosporine 3 mg/kg/day and the twice-daily application of topical tacrolimus
      0.1%.

PMID- 17033175
TI  - Angioma serpiginosum arranged in a systematized segmental pattern suggesting
      mosaicism.
AB  - In a 15-year-old Taiwanese girl, multiple purple punctate lesions arranged in a
      systematized, segmental pattern had developed since childhood, beginning from the
      right thigh and gradually progressing upwards to the right buttock, the left side
      of the abdomen, circumventing to the left side of the back, and extending to the
      right arm as well as to the posterolateral aspect of the left leg.
      Histopathological examination showed dilated capillaries in the uppermost part of
      the dermal papillae characteristic of angioma serpiginosum. The systematized,
      segmental and asymmetric arrangement of lesions as noted in the present case
      suggest that angioma serpiginosum reflects genetic mosaicism.

PMID- 17033176
TI  - Aggressive CD30 large cell lymphoma after cyclosporine given for putative atopic
      dermatitis.
AB  - Atopic dermatitis (AD) is not regarded as a predisposing condition for cutaneous
      T cell lymphoma. Cyclosporine (CsA) is an efficient therapy in AD, and its side
      effects, including lymphocytic proliferation, are rare at the low dose used in
      such cases. So far 3 cases of patients who developed cutaneous T cell lymphoma
      under CsA treatment for atopy have been described. An adult patient with a
      history of AD received CsA therapy because of an atypical flare-up of his
      eruption. He rapidly developed papular atypical lesions, then followed by the
      onset of a voluminous cutaneous tumor leading to the diagnosis of mycosis
      fungoides (MF) transformed in CD30+ large cell lymphoma with nodal and blood
      involvement. No improvement occurred after withdrawing of CsA, and he required a
      polychemotherapy and an allograft. This case illustrates the dramatic evolution
      of an MF under CsA given in the hypothesis of AD. It stresses the fact that skin
      biopsies should be taken in case of atypical AD to rule out MF and avoid such an
      aggressive evolution under immunosuppressive therapy.

PMID- 17033177
TI  - Creeping hair: an isolated hair burrowing in the uppermost dermis resembling
      larva migrans.
AB  - A 55-year-old Japanese male presented with a slowly moving linear erythema that
      looked like an eruption of creeping disease, or cutaneous larva migrans. The
      eruption extended linearly along Langer's line of the lateral side of the abdomen
      to the lower back, leaving wave-like erythema. In the top third of the
      erythematous eruption, close examination demonstrated a black thin line, which
      was revealed to be a hair shaft by a shallow incision of the skin. After removal
      of the hair, the eruption diminished immediately, leaving a slight pigmentation.
      An ingrown pubic hair seemed to have migrated with the lower end forward along
      Langer's line, because of the arrangement of hair cuticle and the force of body
      motion. Linearly moving erythematous eruptions that look like that of larva
      migrans should be differentiated from creeping hair by close examination
      detecting burrowing hair.

PMID- 17033178
TI  - Pseudonits in dreadlocked hair: a louse-y case of nits.
AB  - We report a case of pseudonits in dreadlocked hair, with prominent hair roots of
      shed hair closely resembling Pediculosis humanus capitis infestation.

PMID- 17033179
TI  - Multiple myeloma associated with porphyria cutanea tarda: a possible role of
      bortezomib?

PMID- 17033180
TI  - Generalized interstitial granuloma annulare induced by pegylated interferon
      alpha.

PMID- 17033181
TI  - Koebner phenomenon in dermatomyositis.

PMID- 17033182
TI  - Regressive lichenoid eruption during an acute episode of Q fever.

PMID- 17033183
TI  - Unilateral accentuation of X-linked ichthyosis following thoracotomy for lung
      cancer.

PMID- 17033184
TI  - Verruca vulgaris following treatment with tacrolimus ointment.

PMID- 17033185
TI  - Angioma serpiginosum with extensive lesions associated with retinal vein
      occlusion.

PMID- 17033187
TI  - Human sebaceous glands: how studies of skin surface lipids have provided
      knowledge of their function and control.

PMID- 17033188
TI  - Aging of human sebocytes in vitro induced by exposure to a defined hormone
      environment.

PMID- 17033189
TI  - Potent corticosteroids inhibit lipogenesis in sebaceous glands.

PMID- 17033190
TI  - Differential regulation of Toll-like receptor and CD14 pathways by retinoids and
      corticosteroids in human sebocytes.

PMID- 17033191
TI  - TLR2 and TLR4 polymorphisms are not associated with acne vulgaris.

PMID- 17033192
TI  - Psoriasin and follicular hyperkeratinization in acne comedones.

PMID- 17033193
TI  - Morphological changes in the rat sublingual gland parenchyma with aging.
AB  - BACKGROUND: The characteristics of mucous cells in the aging rat sublingual gland
      were investigated in this study. Particular attention was paid to accumulated
      amyloid protein and changes of the properties of the secretory granules at the
      histochemical and ultrastructural level. OBJECTIVE: This study was designed to
      examine age-related morphological changes in the sublingual gland of male Wistar
      rats from 12 to 27 months. METHODS: For light microscopy, the sublingual glands
      were fixed with 10% neutral-buffered formalin, embedded in paraffin, and
      processed for Alcian blue, Congo red, and TUNEL staining. For transmission
      electron microscopy, some of the samples were fixed with Karnovsky solution,
      postfixed with 2% osmium tetroxide, and embedded in epoxy resin for pronase
      treatment. RESULTS: The sublingual gland showed slight shrinkage after 21 months.
      After 24 months, Congo red staining showed positive reaction to the intralobular
      connective tissue surrounding the terminal portions and to the interlobular
      connective tissue around the blood vessels and the excretory ducts. At 27 months,
      some of the granules in the serous demilunes had difficulty in digesting with
      pronase treatment. The appearance rate of TUNEL-positive cells was low in both
      mucous and serous portions during the observation period, though the positive
      cell number was higher in the serous than in the mucous portion. CONCLUSIONS:
      These findings indicate that the rat sublingual gland accumulates amyloid protein
      in the parenchyma and changes the properties of secretory granules of the acinar
      cells in the serous demilune with aging, though apoptosis of the parenchymal
      cells and the decrease of the gland weight are slight.

PMID- 17033194
TI  - Highlights in cellular and molecular mechanisms of allergic diseases. XXVth
      Congress of the European Academy of Allergology and Clinical Immunology in
      Vienna.
AB  - This year, the annual congress of the European Academy of Allergology and
      Clinical Immunology was held on 10-14 June in Vienna. More than 6,000 delegates,
      practicing bench or bedside work or both, gathered from over 50 countries
      throughout the world. Health professionals, basic scientists and fellows in
      training could choose between a variety of activities in plenary, main,
      educational and workshop sessions, highlights of the past year, pros and cons,
      and oral abstract and poster sessions, and met with experts. A total of 1,713
      abstracts, 31 symposia, and 54 workshops were presented, ranging from basic
      science to clinical trials and modern treatment of allergic diseases. Here, we
      summarize the highlights of cellular and molecular mechanisms of allergic
      disease.

PMID- 17033195
TI  - The role of protein glycosylation in allergy.
AB  - The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are
      the most abundant environmental immune determinants. They are the structural
      basis of what is known as cross-reactive carbohydrate determinants (CCDs).
      Despite some structural variation, the two main motifs are the xylose and the
      core-3-linked fucose, which form the essential part of two independent epitopes.
      Plants contain both epitopes, insect glycoproteins only fucose. These epitopes
      and other fucosylated determinants are also found in helminth parasites where
      they exert remarkable immunomodulatory effects. About 20% or more of allergic
      patients generate specific anti-glycan IgE, which is often accompanied by IgG.
      Even though antibody-binding glycoproteins are widespread in pollens, foods and
      insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all
      patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus
      can be rated as clinical irrelevant allergen. Low binding affinity between IgE
      and plant N-glycans now drops out as a plausible explanation for the benign
      nature of CCDs. This rather may result from blocking antibodies induced by an
      incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday
      contact with plant materials, e.g. fruits or vegetables. The need to detect and
      suppress anti-CCD IgE without interference from peptide epitopes can be best met
      by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single
      beta-arabinofuranosyl residues) has been identified as a new IgE-binding
      carbohydrate epitope in the major mugwort allergen. However, currently the
      occurrence of this O-glycan determinant appears to be rather restricted.

PMID- 17033196
TI  - Tensile residual strains on the elastic lamellae along the porcine thoracic
      aorta.
AB  - AIMS: This study determines the residual strains on the elastic lamellae in the
      porcine thoracic aorta to understand the distribution of strains amongst the
      components of the vascular wall. METHODS: Residual strains in aortic rings were
      released by cutting and purifying the elastin. Strains were calculated from
      lamellar contour lengths based on lamellar waviness and from mechanical tests.
      RESULTS: On the release of residual strains, waviness decreased 2-7%, the inner
      lamellae shortened 2.1 +/- 0.6% and the outer lamellae shortened 7.1 +/- 0.4% (p
      < 0.001), indicating that all lamellar elastin was under tension in fresh aortic
      tissue. Lamellar shortening was 3% greater in the distal than in the proximal
      tissue. Mechanical tests confirmed the morphological results and showed that the
      residual strains in fresh tissue required both the elastic tissue and the
      vascular smooth muscle. Tensile residual strains averaging 1.0% remained in the
      uncut elastin rings. CONCLUSION: When waviness is considered, the residual
      strains on the individual wall components can differ from the surface residual
      strains based only on the ring perimeter. The residual strains on the inner
      elastic lamellae are tensile, not compressive. The strain distribution amongst
      the individual components is non-uniform and not adequately understood to
      determine the physiological strains in the aortic wall.

PMID- 17033197
TI  - Gestational stress leads to depressive-like behavioural and immunological changes
      in the rat.
AB  - Stress during pregnancy, gestational stress, can increase the chance of
      developing postpartum depression, which is estimated to occur in 10% of women.
      Since major depression is accompanied by an activation of the inflammatory
      response system, the aim of this study was to investigate if stress during
      pregnancy induces postpartum depressive-like behaviour, and if so, is it
      accompanied by activation of the inflammatory response system in female Fisher
      rats. We investigated the effect of gestational stress on the production of
      depressive-like behaviour in the rats. The pregnant dams underwent daily
      restraint stress (for 1 week, 3 times/day) or were left undisturbed (control). On
      postpartum day 22, the rats were introduced to the forced swim test (pre-test).
      On postpartum days 23 and 24 (test days), the immobility time was measured.
      Gestational stress significantly elevated immobility scores by 35-40% above the
      control values on both test days, which suggests that the stressed group
      displayed postpartum depressive-like behaviour. The concentrations of the pro
      inflammatory cytokines interleukin-1beta, tumour necrosis factor-alpha and the
      anti-inflammatory cytokine interleukin-10 in stimulated whole-blood culture were
      also analysed. The stressed group showed higher levels of all three cytokines. No
      significant differences in the cytokine concentrations were detected in the
      hypothalamus, hippocampus or pre-frontal cortex.

PMID- 17033198
TI  - Intrathecal immunoglobulin G synthesis and brain injury by quantitative MRI in
      multiple sclerosis.
AB  - OBJECTIVES: It was the aim of this study to evaluate if the quantitative
      intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy
      and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of
      multiple sclerosis (MS) patients. METHODS: A total of 50 patients with relapsing
      remitting MS were included in this study. MRIs were performed and cerebrospinal
      fluid samples were collected during the diagnostic determination when patients
      were in remission without treatment. RESULTS: At study baseline, IgG index values
      were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42
      of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared
      with healthy controls, brain atrophy was observed in MS patients. A positive
      correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was
      observed; the Expanded Disability Status Scale correlated positively with TLV and
      the number of lesions, although a significant relationship between disability and
      brain atrophy was not demonstrated. CONCLUSIONS: Although new parameters will be
      necessary in longitudinal studies to characterize the axonal injury in various
      stages of the disease, the data suggest that the high intrathecal IgG synthesis
      may predict a greater brain lesion burden.

PMID- 17033199
TI  - DNA aptamers that bind to MUC1 tumour marker: design and characterization of MUC1
      binding single-stranded DNA aptamers.
AB  - Agents able to bind tightly and selectively to disease markers can greatly
      benefit disease diagnosis and therapy. Aptamers are functional molecules, usually
      DNA or RNA oligonucleotides, with the appropriate sequence and structure to form
      a complex with a target molecule. MUC1 is a well-known tumour marker present in a
      variety of malignant tumours and it has been a target of interest for many years.
      In this work we report the selection of DNA aptamers that bind with high affinity
      and selectivity to the MUC1 peptides. Combinatorial chemistry techniques based on
      the SELEX methodology were used for the identification of the specific aptamers.
      These were selected from an initial library containing a 25-base-long variable
      region, resulting in 4(25) random sequences of single-stranded DNA molecules, for
      their ability to bind to synthetic forms of MUC1. Ten rounds of in vitro
      selection were performed enriching for MUC1 binding. By round ten more than 90%
      of the pool of sequences consisted of MUC1-binding molecules. Selected aptamer
      families were cloned, sequenced and found to be unique, sharing no sequence
      consensus. The binding properties of these aptamers were quantitated by enzyme
      linked immunosorbent assay and surface plasmon resonance, whereas their
      specificity for MUC1-expressing cancer cells has been validated using fluorescent
      microscopy. Aptamers offer significant advantages over existing antibody-based
      recognition procedures in that they offer higher binding affinity (higher
      retention/reduced dissociation) and specificity to the target (ability to
      determine variations on the protein target down to single amino acid changes),
      higher selectivity against mutated protein epitopes and potentially reduced
      immunogenicity and increased tumour penetration associated with their size.

PMID- 17033200
TI  - Multidrug resistance in locally advanced breast cancer.
AB  - BACKGROUND: Advanced breast cancer cases can still be encountered resulting in
      poor prognosis. The primary treatment for these patients is chemotherapy, and
      multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug
      resistance before first-line chemotherapy may increase the patient's survival. In
      this study, the role of MDR is evaluated in locally advanced breast cancer
      patients. METHODS: Reverse transcriptase polymerase chain reaction was used for
      the detection of MDR genes, ABCB1 and ABCC1. Immunohistochemistry was used for
      the detection of MDR proteins, P-glycoprotein (Pgp) and MDR-associated protein 1.
      RESULTS: Breast tissues from 25 patients both before and after chemotherapy were
      examined. Five patients were unresponsive to chemotherapy. Four had ABCB1 gene
      expression induced by chemotherapy, and Pgp positivity was detected in 9 patients
      after chemotherapy. Both the induction of ABCB1 gene expression (p < 0.001) and
      Pgp positivity (p < 0.001) during chemotherapy were significantly related with
      clinical response. Although 80% of the clinically unresponsive patients had ABCC1
      gene expression, the relation between ABCC1 expression and clinical drug response
      was not significant. CONCLUSION: In locally advanced breast cancer, ABCB1 gene
      expression during chemotherapy contributes to clinical unresponsiveness. However,
      ABCC1 gene expression did not correlate strongly with the clinical response.

PMID- 17033201
TI  - Evaluation of an improved tissue inhibitor of metalloproteinase 1 dual monoclonal
      sandwich immunoassay.
AB  - BACKGROUND: It has previously been shown that increased levels of plasma tissue
      inhibitor of metalloproteinase 1 (TIMP-1) is associated with shorter survival for
      patients with colorectal cancer (CRC). Furthermore, plasma TIMP-1 levels have
      been found to be elevated in patients with early-stage CRC. OBJECTIVE: It was the
      aim of this study to develop a new dual monoclonal antibody (mAb) sandwich
      immunoassay for TIMP-1 in order to achieve better resolution of non-cancer and
      cancer plasma specimens. METHODS: Chemiluminescence immunoassay techniques were
      used to screen 240 combinations of TIMP-1 mAbs for their ability to interact with
      each other and to allow for further characterization of the sandwiching antibody
      pairs. Five mAb pair combinations were selected for assessment of their ability
      to resolve non-cancerous and cancerous plasma specimens by TIMP-1 measurement.
      Based on this testing, a final assay format was chosen for further validation.
      The results for the final assay were compared with measurements obtained in a
      TIMP-1 ELISA that had previously demonstrated the ability to resolve healthy
      blood donors and CRC specimens. RESULTS: The clinical results support that the
      new dual monoclonal immunoassay has statistical discrimination equivalent to the
      ELISA. Additionally, the immunoassay had a high reproducibility and specificity.
      CONCLUSION: The clinical evaluation of five TIMP-1 immunoassays resulted in the
      development of a new immunoassay. The new TIMP-1 immunoassay showed superior
      analytical performance to our previously used ELISA.

PMID- 17033202
TI  - ALDH2 1510 G/A (Glu487Lys) polymorphism interaction with age in head and neck
      squamous cell carcinoma.
AB  - Recent molecular epidemiological studies have revealed a possible association of
      the acetaldehyde dehydrogenase-2 (ALDH2) 1510 G/A (Glu487Lys) polymorphism with
      various cancers including head and neck squamous cell carcinoma (HNSCC). To
      further elucidate the significance of this polymorphism in HNSCC development, the
      relationship between ALDH2 1510 G/A and clinicopathological parameters, cigarette
      smoking or alcohol intake was evaluated in patients with HNSCC. DNA samples from
      192 patients with primary HNSCC and 192 age- and gender-matched healthy controls
      were genotyped and statistically evaluated. Although there was no significant
      difference in the genotype distribution of ALDH2 1510 G/A between cases and
      controls, we found that the frequency of the ALDH2 genotypes with the mutated A
      (Lys) allele was greater in patients aged <66 years than in those aged > or = 66
      years (p = 0.034). This tendency became more evident in patients with the habit
      of drinking (n = 143; p = 0.009). The association of ALDH2 1510 G/A with age
      remained significant after multivariate logistic regression analysis was
      performed for the patients (odds ratio for an age interval for 1 year, 0.970; 95%
      confidence interval, 0.943-0.998). The present data suggest a possible
      interaction between the ALDH2 1510 G/A polymorphism and age in HNSCC.

PMID- 17033203
TI  - Classical Hodgkin's lymphoma: molecular evidence for specific alterations in
      circulating T lymphocytes.
AB  - OBJECTIVE: Impairment in cell-mediated immunity has long been recognized in
      classical Hodgkin's lymphoma (cHL). The immunosuppressive environment at the
      tumor site and/or a primary T-cell defect may contribute to an ineffective immune
      clearance of Hodgkin/Reed-Sternberg (H/R-S) cells. Here, we analyzed whether
      circulating T lymphocytes of cHL patients show specific alterations in gene
      expression with possible impact on anti-tumor immunity. MATERIAL AND METHODS:
      Gene expression profiles were performed from CD3+ T cells isolated from
      peripheral blood samples of untreated patients with cHL versus two control groups
      consisting of healthy donors and patients with sarcoidosis. The regulation of
      gene expression was confirmed in additional patients for selected genes by real
      time RT-PCR. RESULTS AND CONCLUSION: Circulating T cells of cHL show a Th1 immune
      response likely supporting anti-tumor immunity. However, the molecular profile
      reveals an association between cell cycle transition/proliferation and induction
      of immune regulatory genes which may limit an effective anti-tumor immune
      response of differentiated Th1 cells.

PMID- 17033204
TI  - Treatment of locally advanced prostate cancer--the case for radical
      prostatectomy.
AB  - The treatment of clinically locally advanced prostate carcinoma (stage cT3)
      remains controversial. One of the main reasons for this controversy results from
      the substantial staging error attached to the clinical diagnosis cT3 with
      overstaged T2 tumors and understaged node-positive cases. Treatment options in
      this situation include radical prostatectomy, external beam radiotherapy,
      immediate or delayed androgen deprivation treatment and the so-called 'watchful
      waiting'. Acceptable and often surprisingly good tumor-specific survival rates
      have been reported for radical prostatectomy in pT3 series--based on good
      clinical case selection--approaching those of pT2 series. In lymph node-positive
      pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does
      not in lymph node-negative pT3 disease. A benefit of adjuvant external beam
      radiotherapy after radical prostatectomy for pT3 cases in prolonging overall
      survival has not been shown, despite the fact that it can prevent or delay
      biochemical and local recurrence. External beam radiotherapy as the only
      treatment for cT3 disease results in unfavorable tumor-specific survival rates,
      which can be significantly improved with adjuvant hormonal treatment with LHRH
      agonists. If, in case of advanced age and/or significant comorbidity, primary
      hormonal treatment is chosen, early hormonal deprivation therapy seems to offer
      marginal benefits in survival compared to delayed treatment.

PMID- 17033205
TI  - Clinicopathological features of patients with biochemical recurrence after
      radical prostatectomy without progressive rise in serum prostate-specific
      antigen.
AB  - INTRODUCTION: The objective of this study was to characterize clinicopathological
      features of patients with biochemical recurrence after radical prostatectomy who
      did not exhibit a progressive rise in serum prostate-specific antigen (PSA)
      during the follow-up period. MATERIALS AND METHODS: We analyzed data from 162
      consecutive patients who underwent radical prostatectomy for clinically organ
      confined prostate cancer without neoadjuvant hormonal therapy and were followed
      postoperatively for at least 1 year. The serum PSA value was measured using an
      ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and
      biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml. RESULTS: A
      total of 32 patients (19.8%) were diagnosed as having biochemical recurrence.
      Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had
      not shown PSA or clinical progression during a median follow-up of 34 months
      after radical prostatectomy. In these 10 patients, the median time to biochemical
      recurrence was 17 months, the median PSA velocity after biochemical recurrence
      was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4
      ng/ml. There were no clinicopathological parameters except for PSA velocity that
      were significantly associated with the features of these 10 patients. CONCLUSION:
      Because of the presence of a subset of patients with biochemical recurrence after
      radical prostatectomy who will not show a progressive increase in serum PSA
      value, the indication for adjuvant therapy for such patients should be cautiously
      determined considering several factors, such as PSA kinetics.

PMID- 17033206
TI  - Variables which might predict the response to salvage radiotherapy in chinese
      patients with biochemical failure after radical prostatectomy.
AB  - BACKGROUND/AIMS: To evaluate the relationship between the variables and the
      outcomes of salvage radiotherapy (sRT) to find some predictors of sRT. METHODS:
      The medical records of 56 patients receiving sRT for biochemical failure after
      radical prostatectomy (RP) were available for retrospective review. sRT was
      defined as external beam radiotherapy for patients with a continuous increase in
      the prostate-specific antigen (PSA) level of >or=0.2 ng/ml after RP. Response was
      defined as achievement of a PSA nadir of <or=0.1 ng/ml. RESULTS: The mean follow
      up period after sRT was 31.6 months. The predictors of response to sRT were PSA
      doubling time (PSADT) and seminal vesicle invasion. The median PSADT in
      responders was 6.5 months versus 4.0 months in non-responders (OR=1.66, p=0.006).
      The patients with a PSADT of >6 months were all responders. The response rate in
      patients with seminal vesicle invasion was 42.9% (6/14) versus 76.2% (32/42) in
      patients without seminal vesicle invasion (OR=0.119, p=0.015). CONCLUSION: PSADT
      and the state of seminal vesicle invasion were good predictors of response to
      sRT. sRT was especially effective when the PSADT was >6 months and in patients
      without seminal vesicle invasion.

PMID- 17033207
TI  - The use of erythropoietin in patients undergoing radical prostatectomy: effects
      on hematocrit, transfusion rates and quality of life.
AB  - OBJECTIVE: It was the aim of this study to prospectively study the effects on
      hematocrit levels, transfusion rates and quality of life (QOL) indices in men
      preoperatively supplemented with recombinant erythropoietin (rEPO) undergoing
      radical prostatectomy for clinically localized prostate cancer. METHODS: Thirty
      men undergoing radical prostatectomy were randomized either to receive rEPO
      (n=25) or to serve as controls (n=25). Outcome measurements obtained
      preoperatively, as well as 10 days and 6 weeks postoperatively included serum
      hematocrit levels, transfusion rates and QOL indices (using SF-12 validated
      questionnaires). RESULTS: The rEPO group had a significant increase in
      preoperative hematocrit (median increase=4 points; p=0.002). Although there were
      no significant differences in hematocrit at 10 days, the rEPO had a significantly
      higher hematocrit value at 6 weeks (p=0.0086). No differences were observed in
      transfusions rates between groups (4% in each group). SF-12 mental and SF-12
      physical scores were not different between the two groups at any time point.
      CONCLUSION: Preoperative administration of rEPO significantly increases
      preoperative and postoperative hematocrit levels. However, no differences were
      observed with regard to transfusion rates or postoperative QOL indices despite
      these higher hematocrit values.

PMID- 17033208
TI  - Laparoscopic radical prostatectomy in patients following transurethral resection
      of the prostate.
AB  - OBJECTIVES: Previous transurethral resection of the prostate (TURP) was reported
      to impose difficulties during open radical prostatectomy. We describe our
      experience in laparoscopic radical prostatectomy (LRP) following transurethral
      resection of the prostate. PATIENTS AND METHODS: The series included 35 patients:
      22 patients underwent transperitoneal LRP (tpLRP) and 13 underwent
      extraperitoneal LRP (epLRP). The minimal interval between TURP and laparoscopy
      was 3 months. Patients' charts were reviewed for their preoperative
      characteristics, intraoperative difficulties and complications, and outcome.
      RESULTS: Patients' mean age was 67.5+/-4.4 years. 12 patients were cT1a,b and 23
      patients were cT1c/T2. Twenty-two patients underwent tpLRP and 13 underwent
      epLRP. No statistical difference was found between the preoperative
      characteristics and the pathological results of cT1a,b vs. T1c/cT2 patients, or
      tpLRP vs. epLRP patients. Thirty-three procedures were completed laparoscopically
      and 2 were converted to open surgery. Perioperative complications included two
      leaking anastomoses, prolonged lymph drainage in 1 case, atelectasis (n=1) and
      duodenal ulcer (n=1). Twelve positive margins were noted, half of them in pT2
      tumors. The mean follow-up was 28.5 months. Twenty-five of 35 patients had more
      than 12 months of follow-up. Among them 19 patients were completely continent
      (76%) and 6 (24%), reported mild stress incontinence. CONCLUSIONS: Although LRP
      following TURP is sometimes more technically difficult, simple modifications in
      the operative strategy help facilitate surgery. LRP following TURP favorably
      compares to open radical prostatectomy after TURP and laparoscopy in non-TURP
      patients.

PMID- 17033209
TI  - How far is the preoperative Kattan nomogram applicable for the prediction of
      recurrence after prostatectomy in patients presenting with PSA levels of more
      than 20 ng/ml? A validation study.
AB  - OBJECTIVE: We present an external validation study investigating the
      applicability of the preoperative Kattan nomogram for predicting recurrence after
      prostatectomy in a population of patients with serum prostate-specific antigen
      (PSA) levels exceeding 20 ng/ml. MATERIALS: In the evaluation of clinical
      parameters pooled from a total of 191 patients presenting with PSA levels ranging
      between 20.1 and 100 ng/ml, the PSA-free survival rate 60 months after surgery
      was calculated according to Kattan nomograms. Subsequently, the results were
      statistically compared with the corresponding actual survival rates obtained from
      Kaplan-Meier analysis. For this purpose, the patients were assigned to one of
      four different risk groups according to predictions derived from the Kattan
      nomograms, enabling a direct comparison of expected (as predicted by Kattan
      nomogram) versus actual survival of each patient investigated in our study.
      RESULTS: Predicted PSA-free survival rates were determined to be as follows: 83%
      (low risk group); 66% (intermediate risk group); 39% (intermediate-high risk
      group), and 10% (high risk group) in comparison with the actual survival rates
      determined to be 63, 62, 40 and 21%, respectively. For PSA levels ranging between
      20.1 and 30 ng/ml, 30.1 and 50 ng/ml, and 50.1 and 100 ng/dl, PSA-free survival
      rates were found to be 57, 37, and 27% (p=0.0017), respectively, during a 5-year
      post-prostatectomy follow-up. CONCLUSIONS: The Kattan nomogram shows good
      statistical concordance with actual survival rates in the mean risk quadrants,
      but considerable differences were demonstrated concerning individuals with either
      a high or with a low risk of cancer progression.

PMID- 17033210
TI  - Validity and reliability of the arabic version of the National Institutes of
      Health Chronic Prostatitis Symptom Index.
AB  - INTRODUCTION: In order to accurately assess the extent of chronic pelvic pain
      syndrome (CPPS) and to objectively measure symptoms for natural history studies
      and to assess the outcome parameters for clinical trials, the National Institutes
      of Health (NIH) Chronic Prostatitis Collaborative Research Network developed and
      validated the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). The aim of the
      current study was to develop and validate a fluent and comprehensive Arabic
      version of the NIH-CPSI. METHODS: This study consisted of 80 consecutive male
      patients affected by CPPS and 80 healthy controls who were asked to complete the
      Arabic version of the NIH-CPSI. The translation was performed by a group
      consisting of an andrologist and professional translators. Psychometric data were
      collected. RESULTS: Of the 160 subjects enrolled, 82 (50 patients and 32
      controls) completed the study. The total Arabic NIH-CPSI scores and the scores of
      each subscale differed significantly between the two groups with good
      discriminant validity. The questionnaire had also a high internal consistency.
      CONCLUSION: The present study provides the Arabic version of the NIH-CPSI and
      recognizes it as a valid and reliable tool in the assessment of local patients
      with CPPS.

PMID- 17033211
TI  - Is the determination of the soluble interleukin-2 receptor after application of
      interleukin-2 receptor antibodies still appropriate for immunological monitoring
      after renal transplantation?
AB  - INTRODUCTION: The use of monoclonal antibodies against the alpha-chain of the
      membrane-bound interleukin-2 receptor (IL-2Ralpha) as immune suppressants causes
      characteristic changes in the levels of soluble interleukin-2 receptor (sIL-2R)
      in serum and urine. METHODS: 38 kidney transplant patients were included in this
      study. 28 of them received an induction therapy with the IL-2R antibody
      basiliximax (Simulect) in addition to standard immunosuppression, 10 patients
      constituted the control group. RESULTS: Time courses of sIL-2R levels of Simulect
      patients with and without complications after transplantation have been compared.
      It turned out that of a total of 18 cases with complications 15 cases could be
      identified by their elevated sIL-2R levels, which corresponds to a sensitivity of
      83%. CONCLUSION: Acute rejection, CMV infection, extrarenal bacterial infection
      and pyelonephritis in the transplant all cause a significant increase of the sIL
      2R level even after application of Simulect.

PMID- 17033212
TI  - Upper urothelial tumors in emigrants from Balkan endemic nephropathy areas in
      Serbia.
AB  - AIM: The aim of the study was to investigate upper urothelial tumors (UUT) in
      emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them
      with UUT from both endemic and nonendemic areas. MATERIALS AND METHODS: A total
      of 1,121 patients from the state cancer database, between 1960 and 1998, were
      investigated. Sixty of them were emigrants from BEN areas. RESULTS: UUT in
      emigrants from BEN areas occurred after 21.7+/-9.9 years (median 20) spent in a
      rural environment. The time spent outside of the BEN regions was 33.2+/-12.8
      years (median 31, range 10-72). Age at surgery was 55 years (range 31-89). In
      emigrants from BEN areas, there was a significant association of other diseases
      with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7%
      of the patients. Bilateralism was statistically more frequent in emigrants from
      BEN areas (p=0.04), as were low-grade tumors (p=0.03). There was no statistical
      difference in tumor stage between patients from BEN areas and from outside of
      them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT
      and both of them (33%). CONCLUSIONS: It is concluded that hereditary as well as
      environmental factors are important for the expression and evolution of the
      disease. An early period of life spent in the endemic region seems important for
      the later development of UUT in emigrants from BEN regions. Different time spans
      spent in the endemic region have no effect on the age of appearance of UUT.

PMID- 17033213
TI  - Comparison of ileal conduit and transureteroureterostomy with ureterocutaneostomy
      urinary diversion.
AB  - INTRODUCTION: We compare the postoperative early and late complications of
      patients who had undergone ileal conduit (IC) urinary diversion and
      transureteroureterostomy (TUU) with ureterocutaneostomy (UC) urinary diversion
      during the same interval and by the same surgeons. MATERIALS AND METHODS: Between
      1992 and 2004, we performed TUU with UC urinary diversion in 27 men and 7 women
      (group I) and ileal conduit urinary diversion in 57 men and 10 women (group II).
      The mean age of the TUU with UC diversion and the ileal conduit patients was 57+/
      11.2 (range 51-76) and 64+/-12.6 (range 54-76) years, and the mean follow-up was
      37 (range 14-52) and 56 (range 14-72) months, respectively. The 6F or 8F stents
      were used routinely. RESULTS: Of 34 TUU with UC cases 8 (23.52%) had early
      postoperative complications and 2 (5.88%) had early reoperation rates, whereas 11
      (16.42%) of 67 ileal conduit cases had early postoperative complications and 4
      (5.97%) had early reoperation. The mean hospital stay was 7 (range 5-25 day) and
      11 (range 7-34 day) days for each group, respectively. Of the TUU and UC cases, 6
      (17.64%) had late complications and 3 had (8.82%) late reoperation, whereas 14
      conduit cases (20.89%) had late complications and 6 had (8.9%) late reoperation.
      Early postoperative complications were defined as those that occurred before
      hospital discharge or within 30 days from the date of surgery and late
      complications were defined as those occurring greater than 30 days from the date
      of surgery as previously described. In group I, the mean operative time was 170
      min (range 120-325) compared with 260 min (range 170-473) in group II. The mean
      blood loss in group I was 474 ml (range 250-1,400) and 589 ml (range 300-1,700)
      in group II (p>0.05). CONCLUSIONS: Our results suggest that patients undergoing a
      TUU and UC diversion have no additional risk of reoperation and the TUU with UC
      urinary diversion is a safe procedure with postoperative early and late
      complications.

PMID- 17033214
TI  - Are lower urinary tract symptoms associated with erectile dysfunction in aging
      males of Taiwan?
AB  - INTRODUCTION: This study was conducted to evaluate the relationship between lower
      urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging males of
      Taiwan. PATIENTS AND METHODS: A free health screening for aging males (>or=45
      years old) was conducted in Kaohsiung Medical University Chung-Ho Memorial
      Hospital in August 2004. LUTS and ED were assessed by validated symptom scales:
      the International Prostate Symptom Score (IPSS) and the International Index of
      Erectile Function-5 (IIEF-5). The subjects also completed a health and
      demographics questionnaire and underwent detailed physical examination, serum
      prostate-specific antigen level determination, and transrectal ultrasonography.
      RESULTS: The final study population consisted of 141 patients with a mean age of
      59.8 years. The severity of LUTS and ED increased with age. After controlling for
      comorbidities, age (p<0.001) and IPSS score (p<0.001) were significantly
      associated with the IIEF-5 score. Furthermore, men with moderate to high IPSS
      scores were more likely to have ED as compared with those with mild symptoms
      after age adjustment (age-adjusted odds ratio 3.27, p=0.002). CONCLUSIONS: ED and
      LUTS are highly prevalent in our study population, and this prevalence increases
      with age. ED is significantly associated with the severity of LUTS after
      controlling for age and comorbidities. These results highlight the clinical
      importance of evaluating LUTS in patients with ED and the need to consider sexual
      issues in the management of patients with benign prostatic hyperplasia.

PMID- 17033215
TI  - Hypoxia-inducible factors HIF-1alpha and HIF-2alpha expression in bladder cancer
      and their associations with other angiogenesis-related proteins.
AB  - Hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) are closely related protein
      complexes that activate transcription of target genes in response to hypoxia. The
      immunohistochemical expression of these two proteins was investigated in 144
      bladder cancer tissue samples and correlated with standard clinicopathological
      features, in order to elucidate their prognostic significance. We also evaluated
      their possible associations with other angiogenesis related markers such as
      microvessel density (MVD), vascular endothelial growth factor, thymidine
      phosphorylase, tenascin, fibronectin, p53 and bcl-2 to further clarify their
      implication in tumor stroma vascularization. Nuclear HIF-1alpha expression in
      tumor cells was detected in 57.1% of the cases. A trend of correlation of this
      expression with poorly differentiated tumors was observed. In addition, HIF
      1alpha expression was positively correlated with stromal cells thymidine
      phosphorylase expression. Tumors that were progressed in muscle-infiltrating
      disease showed a higher HIF-1alpha expression. A higher HIF-1alpha expression was
      also observed in tumors with an in situ component. In tumor cells, low HIF-2alpha
      expression was observed in 6.3%, moderate in 31.9% and high in 61.8% of the
      cases. A trend of correlation of this expression with MVD was observed. In
      addition, HIF-2alpha expression was positively correlated with thymidine
      phosphorylase and fibronectin expression. A lower HIF-2alpha expression was
      detected in tumors that recurred earlier in univariate methods of analysis. HIF
      2alpha was expressed in tumor stroma associated cells in 53.5% of specimens and
      was correlated with advance tumor stage, thymidine phosphorylase and tenascin
      expression. There was no statistically significant difference in the expression
      of both HIF-1alpha and HIF-2alpha between primary and recurrent tumors. In
      multivariate analysis including T stage, T grade, multifocality and T size, both
      HIF-1alpha and HIF-2alpha expression were not considered dependent in the
      prediction of recurrence or progression. In conclusion, the results of the
      present study indicate that HIF-1alpha and HIF-2alpha expression may help to
      predict recurrence or progression to muscle invasive disease but not as
      independent prognostic factors. In addition, the expression of HIF-1alpha and HIF
      2alpha, appear to play a role in bladder cancer, vascularization possibly and in
      cooperation with other angiogenic factors.

PMID- 17033216
TI  - Effects of propylthiouracil on testicular tissue in undescended testes of newborn
      rats.
AB  - AIM: The most important goal in the treatment of cryptorchidism is to preserve
      the potential for fertility. This experimental study was performed to investigate
      the effect of propylthiouracil (PTU) on the undescended testes (UTs) of newborn
      rats. MATERIALS AND METHODS: The experimental cryptorchidism model in newborn
      male rats consisted of 4 groups. The groups A (control) and B (PTU) underwent no
      surgical intervention, whereas in groups C (UT only) and D (treatment) UTs were
      produced by dissecting and suturing the future right scrotal area. In groups D
      and B, 0.1% (w/v) PTU was added to the drinking water of mother rats between 2
      and 24 days. At the end of the 90th day rat body weights, testicular weights,
      Johnsen tubular biopsy scores (JTBSs), seminiferous tubule diameters (STDs),
      testosterone, and thyroid hormone levels were measured. Mann-Whitney U test was
      used for statistical analysis. RESULTS: Mean testicular weight was similar
      between groups A, B and D, and statistically lowest in group C. Mean body weight
      was statistically higher in groups A and C compared with groups B and D. Mean
      testosterone levels showed no statistical difference between the groups. Mean
      JTBSs were statistically higher in groups A and B compared with groups C and D.
      The value in treatment group D was statistically higher compared to group C
      (p<0.05). Mean STDs were statistically lowest in group C compared to other groups
      (p<0.05). No difference was found between groups A, B, and D (p>0.05). Both the
      mean free triiodothyronine and free thyroxine values between groups A and C and
      between groups B and D were similar. The values in groups A and C were
      statistically higher than those of groups B and D (p<0.05). CONCLUSION: PTU
      induced transient hypothyroidism in the newborn rat UT model shows protective
      effects on testicular growth parameters.

PMID- 17033217
TI  - Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced
      prostate growth in rats.
AB  - INTRODUCTION: This study was undertaken to investigate the effects of pumpkin
      seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T
      P) prostate growth in rats. MATERIALS AND METHODS: Forty adult Wistar rats were
      divided into five groups, including: one control group, rats treated with vehicle
      only, one group treated with T-P, and two groups of T-P-treated rats, one
      receiving orally pumpkin seed oil alone and one group receiving orally pumpkin
      seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to
      body weight ratio was determined after sacrifice. The total protein concentration
      was measured by using a protein assay. Some ventral prostatic tissues were
      histologically examined after hematoxylin-eosin staining. RESULTS: Histological
      sections of the ventral prostate showed that the architecture of the prostate
      glands became hyperplastic in the T-P rats, but not in the control or vehicle
      treated animals. As compared with the control or vehicle group, T-P rats had a
      significantly higher prostatic weight-to-body weight ratio for the ventral
      prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral
      prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher
      protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001,
      respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared
      with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or
      pumpkin seed oil combined with Phytosterol-F had a significantly lower weight
      ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and
      significantly lower protein levels within both lobes (p=0.03 and p=0.003,
      respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had
      some additive effect on the total protein synthesis within the ventral prostate
      (p=0.02). CONCLUSION: Pumpkin seed oil alone or combined with Phytosterol-F can
      block the T-P-induced increases in prostatic weight-to-body weight ratio and
      protein synthesis.

PMID- 17033218
TI  - Long-term influence of prepubertal testicular torsion on spermatogenesis.
AB  - PURPOSE: To study the influence of prepubertal unilateral testicular torsion on
      spermatogenesis postpubertally. METHODS: Sixty prepubertal SD male rats were
      divided into 6 groups. In each group, animal suffered different courses of
      unilateral testicular torsion including sham operation, 2- and 6-hour-long
      torsion, and permanent torsion. Salvia miltiorrhiza was injected as a remedy to
      release the I/R injury in the 2- and 6-hour-long torted groups. Postpubertally,
      the percentage of DNA content of haploid cells in the testes was determined
      individually. RESULTS: The percentage of haploid cells in the sham operation
      group was 76.5+/-1.9%. The number decreased in every other group (p<0.01).
      Comparing with the same course of torsion, Salvia miltiorrhiza injection could
      improve the percentage of haploid cells (p<0.01). In the permanent unilateral
      testicular torted group, the percentage was nearly zero (0.4+/-0.2%).
      CONCLUSIONS: Prepubertal unilateral testicular torsion induces decreased
      spermatogenesis postpubertally. The result takes place in the bilateral testes.
      Salvia miltiorrhiza, as an antioxidant remedy, could relieve the injury which
      manifests improved spermatogenesis.

PMID- 17033219
TI  - Primary bladder dermoid: a case report and review of the literature.
AB  - Bladder dermoid is a rare presentation. Diagnosis of this case was made
      cystoscopically and confirmed histopathologically. Complete excision was possible
      endoscopically. This is the 3rd case report from the Indian and Asian
      subcontinent.

PMID- 17033220
TI  - A 7-year history of an intratesticular mass: patient description and review of
      the literature about dermoid cysts of the testis.
AB  - A dermoid cyst is a particular form of a cystic teratoma. In the testis, it is
      very rare, with only a few cases reported in world literature. A 19-year-old
      patient come to our attention with a 7-year history of an intratesticular cystic
      mass. Sonography showed a large hypoechoic solid mass. The tumour markers alpha
      fetoprotein, beta-human chorionic gondatotrophin, and lactate dehydrogenase were
      negative. Chest X-ray was negative. He underwent surgical exploration of the
      right testis and enucleation of the mass with testis preservation. At 14 month of
      follow-up, the patient had no complications and no recurrence of the lesion.
      Surgical enucleation is the treatment of choice in consideration of hormonal,
      psychological, and reproductive aspects. Orchiectomy should have been the
      treatment of choice, if the mass had substituted all testicular parenchyma and if
      there had been some malignant transformations.

PMID- 17033221
TI  - The unbreakable bladder stone--Munchhausen's tale.
AB  - A wide range of intra-vesical foreign bodies have been described in the
      literature. Causes include iatrogenic, migration from adjacent organs,
      penetrating injuries and self-insertion, either due to eroticism, inquisitiveness
      or as a result of a psychiatric illness. We present an unusual case of fictitious
      bladder stones that proved unbreakable using all standard endourological
      techniques.

PMID- 17033222
TI  - Intermittent ureteral herniation--rare cause of flank pain.
AB  - Ureteral herniation is rare and difficult to diagnose, especially when
      intermittent, and ureterocystoneostomy using the psoas hitch or boari flap
      techniques have so far been used as therapeutic options. We describe ureterolysis
      in two cases as a successful alternative approach.

PMID- 17033223
TI  - [Problems associated with molecular targeted drugs for cancer].
AB  - Molecular targeted drugs have been developed and have come to play a part in the
      standard treatment of cancers. However, issues such as the optimum dose,
      selection of patients, and verification of the molecular targets remain to be
      discussed, because unexpected clinical problems related to the clinical efficacy,
      adverse events, and development of resistance have appeared. Therefore, proof of
      principle (POP) studies and pharmacodynamic or pharmacogenomic research to
      explore new bio-markers for the drugs are essential for clinical progress. On the
      other hand, the higher cost of development and care must also be discussed as new
      problems.

PMID- 17033224
TI  - [Reasons for the increased incidence of skin cancer].
AB  - The cutaneous malignancies with an increasing incidence in Japan are squamous
      cell carcinoma, basal cell carcinoma, and malignant melanoma. As a precancerous
      state or early lesion, actinic keratoses also deserve attention. According to a
      nationwide questionnaire survey (responses from 94 centers), basal cell carcinoma
      has the highest incidence and accounts for nearly 50% of all skin malignancies,
      followed by squamous cell carcinoma (31%) and malignant melanoma (21%). The
      number of cases of each tumor has grown annually, and comparison of the percent
      increases between 1987 and 2001 shows an increase of about 1.5-fold for basal
      cell carcinoma or 1.7-fold for squamous cell carcinoma or malignant melanoma.
      Supported by a Grant-in-Aid for Cancer Research from the Ministry of Health,
      Labor and Welfare, the Malignant Skin Tumor Research Group has been investigating
      the factors behind these increases by detailed statistical analysis of data
      obtained from 1987 onwards from designated centers (19-22 centers). Numerous
      factors have been suggested by this research, but the most important was
      concluded to be ultraviolet radiation.

PMID- 17033225
TI  - [Melanoma].
AB  - The definition of the TNM classification and staging system of malignant melanoma
      have been fundamentally revised. Moreover, several clinical guidelines for the
      management of this neoplasm were recently proposed. Advances in surgical
      procedures are excision of primary lesions with narrow margin and introduction of
      sentinel node biopsy, which contribute to maintain the good quality of life of
      patients. The significance of high-dose interferon-alpha as adjuvant therapy is
      still controversial. No effective chemotherapy or biotherapy has been established
      to date, however, interesting new findings were recently reported in the fields
      of immunotherapy and molecular targeting therapy.

PMID- 17033226
TI  - [Squamous cell carcinoma].
AB  - Squamous cell carcinoma of the skin is common skin malignancy arising from
      malignant proliferation of the keratinocytes of the epidermis. Chronic exposure
      to ultraviolet radiation in sunlight is the most important risk factor for
      squamous cell carcinoma. Early diagnosis and appropriate treatment provide the
      best opportunity to cure cutaneous squamous cell carcinomas. Although it is
      locally invasive, squamous cell carcinomas usually remain localized and can be
      cured by a variety of techniques. Surgical excision is the most broadly used
      treatment for high-risk squamous cell carcinoma. It is well-tolerated, extremely
      effective, and the completeness of the procedure can be evaluated through
      histologic assessment of the specimen's margins. About 10 percent of squamous
      cell carcinomas in Japan spread to regional lymph nodes or more distant sites
      with a relatively poor outcome. Five-year cure rates are reported to be 85 to 80
      percent for Japanese patients with squamous cell carcinomas, respectively.
      Recommendations for surgical margins vary depending upon the risk of local
      recurrence, especially; squamous cell carcinomas with perineural extension also
      need more extensive procedures. Patients with clinically enlarged lymph nodes may
      require radiographic imaging, fine needle aspiration, or lymph node biopsy.
      Depending upon the results of these tests, regional lymph node dissection may be
      done. Recently the sentinel lymph node biopsy technique is being evaluated for
      its ability to detect microscopic involvement in patients with high-risk patients
      who have no clinical evidence of lymph node metastasis. The occurrence of
      regional lymph node metastases places the patient at increased risk for the
      subsequent development of distant metastases. Distant metastases are associated
      with a markedly increased risk of disease-related mortality. Systemic
      chemotherapy has been to limited benefit in patients with disseminated squamous
      cell carcinoma patients. In Japanese patients with distant metastases, the five
      year survival rate is about 10 percent. The ability of current chemotherapy
      protocols to increase the cure ratio in squamous cell carcinoma is still
      controversial.

PMID- 17033227
TI  - [Basal cell carcinoma].
AB  - Basal cell carcinoma (BCC) is the most common skin cancer. It tends to be locally
      invasive but rarely metastasizes. Dermoscopy has been reported as a useful in
      vivo method for the accurate clinical diagnosis of BCC. The first-line treatment
      for BCC is surgical excision, however, clinical trials of non-surgical treatment
      modalities such as topical imiquimod and photodynamic therapy have recently been
      published in the English literature, and are gradually being introduced into
      Japan. Although clinical practice guidelines for the management of BCC have been
      already published in several countries, original guidelines for Japan are
      required in light of clinical and ethnic differences.

PMID- 17033228
TI  - [Extramammary Paget's disease].
AB  - The treatment strategy for extramammary Paget's disease depends on the presence
      of metastasis. For the group of patients with primary tumor limited to the
      epidermis, the aim of treatment is local control by precise detection of the
      tumor margin. For patients without indications for surgery, radiotherapy or
      photodynamic therapy would be the treatment of choice. On the other hand, the
      prognosis of patients with distant metastases is desperate. Although a limited
      response to combination chemotherapy was observed, no survival benefit has been
      proven yet. New modalities of treatment such as molecular targeting drugs and
      hormonal therapy are expected.

PMID- 17033229
TI  - [Multicenter phase II trial of thrice-weekly docetaxel and weekly trastuzumab as
      preoperative chemotherapy in patients with HER 2-overexpressing breast cancer-
      Japan East Cancer Center Breast Cancer Consortium (JECBC) 02 Trial].
AB  - The efficacy and safety of combination therapy of 4 cycles with docetaxel 70
      mg/m(2)every 3 weeks and trastuzumab as primary chemotherapy for operable breast
      cancer was determined in 21 patients (pts) by assessing the pathological complete
      response (pCR) rate, clinical response rate (RR), breast conservation surgery
      (BCS) rate and toxicities. To date, 19 pts have completed surgery. The pCR rate
      was 21% [95% CI 6%-46%] . The overall RR was 90% [95% CI 67%-99%] , with 5 CR, 12
      PR, 2 SD and 0 PD. Grade 3 or 4 adverse events were leukopenia 48%, neutropenia
      67%, hemoglobin 5%, and febrile neutropenia 10%. All non-hematological toxicities
      were mild and manageable. The pCR rate is not as low as that achieved in previous
      international studies. The combination of docetaxel and trastuzumab was a well
      tolerated and very active regimen for the treatment of patients with HER 2
      overexpressing operable breast cancer. This regimen promises to be one of the
      leading future treatments for progressive breast cancer.

PMID- 17033230
TI  - [Adjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel for
      Japanese women with node-positive breast cancer: a multi-institutional
      feasibility study in a variety of practice settings in Kyushu].
AB  - We evaluated the feasibility of doxorubicin plus cyclophosphamide (AC) followed
      by weekly paclitaxel (wT) as adjuvant therapy for node-positive breast cancer in
      a variety of practice settings. Forty-seven patients received AC at either doses
      of 40 mg/m(2)+400 mg/m(2) (A(40)C(400), 33 patients) or 50 mg/m(2)+500 mg/m(2)
      (A(50)C(500), 14 patients) every 3 weeks for 4 cycles followed by wT at a dose of
      80 mg/m(2)for 12 cycles with a week pause after 3 consecutive weekly
      administrations. Mean relative dose-intensities were 98.8% for A(40)C(400), 90.7%
      for wT after A(40)C(400), 91.3% for A(50)C(500), and 89.2% for wT after
      A(50)C(500). Grade 4 toxicity included neutropenia (3.0% for A(40)C(400), 14.3%
      for A(50)C(500)). Grade 3 toxicity included neutropenia (18.2% for A(40)C(400),
      28.6% for A(50)C(500), 6.7% for wT), thrombocytopenia (2.2% for wT),
      nausea/vomiting (6.1% for A(40)C(400)), anorexia (3.0% for A(40)C(400), 2.2% for
      wT), fatigue (3.0% for A(40)C(400)), AST/ALT elevation (7.1% for A(50)C(500)),
      allergic reaction (4.4% for wT). There were six (12.8%) treatment
      discontinuations, including two allergic reactions to paclitaxel. AC followed by
      wT can be administered safely in the community at doses of 50 mg/m(2), 500
      mg/m(2), and 80 mg/m(2), respectively,with minimal toxicity.

PMID- 17033232
TI  - [Therapeutic efficacy of capecitabine on advanced and recurrent breast cancer
      with special reference to time to progression].
AB  - We investigated 29 patients with advanced and recurrent breast cancers who
      underwent capecitabine therapy in the department. Patients'backgrounds: 41-89
      years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent
      breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six
      percent of patients were positive for ER and/or PgR. Multiorgan metastases
      occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases;
      skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who
      received chemotherapy was 93%, and the rate of those who received
      endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5
      cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a
      response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression
      (TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was
      2-23 months (median length, 12 months). OS was significantly longer in patients
      who had therapeutic effects than in patients with no such effects. TTP was
      significantly longer in patients who had therapeutic effects and in those who had
      longer SD than in patients with no such effects. OS was significantly longer in
      patients who had TTP of 6 months or longer. Clinical benefit (presence vs.
      absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP.
      Capecitabine is expected to prolong the length of survival in patients who are
      able to continue treatment for 6 months or longer.

PMID- 17033231
TI  - [A randomized controlled study comparing uracil-tegafur (UFT)+tamoxifen (UFT+TAM
      therapy) with cyclophosphamide+adriamycin+5-fluorouracil (CAF therapy) for women
      with stage I , II, or IIIa breast cancer with four or more involved nodes in the
      adjuvant setting].
AB  - We performed a controlled study to compare the response to cyclophosphamide
      (CPA), adriamycin (ADM), and fluorouracil (5-FU) (CAF therapy) with that to
      uracil-tegafur (UFT) plus tamoxifen (TAM) (UFT+TAM therapy), when given as
      postoperative adjuvant therapy to women with breast cancer. The patients were
      registered from September 1991 through February 1995 at 51 institutions in the
      Kinki district of Japan. All patients had stage I, II, or IIIa breast cancer with
      four or more lymph-node metastases and underwent mastectomy. CAF therapy and
      UFT+TAM therapy were started within 4 weeks after surgery. CAF therapy consisted
      of CPA (100 mg/day) on days 1 to 14, followed by 2 weeks of rest, plus ADM (20
      mg/m(2)/day) on days 1 and 8 and 5-FU (300 mg/m(2)/day) on days 1 and 8. A total
      of 6 courses were delivered. UFT+TAM therapy consisted of 3 years of UFT (400
      mg/day) plus TAM (20 mg/day), given daily. CAF therapy and UFT+TAM therapy were
      each assigned to 82 patients. The 5-year survival rate was significantly higher
      in the UFT+TAM group (82.1%) than in the CAF group (66.2%; p=0.04, logrank test).
      The 5-year relapse-free survival rate was higher in the UFT+TAM group (61.8%)
      than in the CAF group (46.3%; p=0.07, logrank test). As for adverse events, the
      rates of leukopenia, anorexia, nausea and vomiting, general malaise, and hair
      loss were lower in the UFT+TAM group than in the CAF group. These results suggest
      that long-term treatment with UFT+TAM may be a useful alternative adjuvant
      therapy for the management of breast cancer, especially in elderly patients.

PMID- 17033233
TI  - [Prolonged survival of gefitinib treatment in patients with advanced and
      previously treated non-small cell lung cancer].
AB  - The purpose of this study was to evaluate the survival outcome in patients with
      advanced and previously treated non-small cell lung cancer given gefitinib (GEF)
      at our institution. We reviewed the clinical records of 70 Japanese
      patients,among whom 33 received several chemotherapy treatment modalities
      including GEF monotherapy (GEF group), and the other 37 were given several
      chemotherapy treatment modalities without GEF monotherapy (non-GEF group). The
      median survival time (MST) after second-line chemotherapy in the GEF group was
      527 days with 1-year and 2-year survival rates of 59% and 26%, respectively. The
      MST in the non-GEF group was 175 days with 1-year and 2-year survival rates of
      21% and 16%, respectively. Overall survival after second-line chemotherapy in the
      GEF group was significantly longer than in the non-GEF group (hazard ratio 1.93;
      95% confidence interval 1.15-3.53, p=0.014). In our limited clinical experience,
      chemotherapy treatment including GEF monotherapy appeared to have longer survival
      than non-GEF treatment.

PMID- 17033234
TI  - [Effectiveness of preoperative chemoradiotherapy for advanced rectal cancer].
AB  - To determine the pathologic effectiveness of preoperative chemoradiotherapy (CRT)
      in patients with advanced rectal carcinoma, we reviewed clinical records of 76
      patients who received preoperative pelvic radiation +/- chemotherapy. Since 2
      patients refused operation and 2 died before surgery, 72 patients underwent
      operation with a mean delay of 19.9 days after completion of irradiation.
      Pathologic tumor regression grade (Grade 0-3) was determined by the amount of
      viable tumor versus necrosis and fibrosis. Grade 0, 1 a, 1 b, 2, and 3 (pCR) were
      observed in 0%, 25.0%, 38.9%, 27.8% and 2.8% of patients, respectively. The
      pathologic response (PR) rate was 75.0% when PR was defined as greater than grade
      1 b (tumor regression more than 1/3). Downstaging was observed in 35.8% of
      patients, in which 5-year overall survival was significantly better than in
      patients without downstaging (90.0% vs. 50.1%, p<0.05). No correlation could be
      observed between PR and downstaging. CRT is a useful tool with a high PR rate in
      patients with advanced rectal cancer. More accurate and careful clinical staging
      is important to select adequate candidates for CRT. Multi-institutional clinical
      trials as well as standardizing the surgical procedure including LN dissection
      are required to validate the advantages of CRT for Japanese patients.

PMID- 17033235
TI  - [Combined chemotherapy with weekly paclitaxel and carboplatin for recurrent and
      refractory epithelial ovarian cancer--phase I study].
AB  - The current initial standard chemotherapy for advanced ovarian cancer is a
      regimen with a combination of platinum and taxane. However, the 5-year survival
      rate remains at 40% or lower, and the recurrence rate is as high as 70-80%.
      Second-line chemotherapy for recurrent cases has not yet been established. We
      conducted a phase I study of combined chemotherapy with paclitaxel (TXL) and
      carboplatin (CBDCA) administered weekly for recurrent and refractory ovarian
      cancer. The subjects were patients with a histopathologically confirmed diagnosis
      of malignant epithelial ovarian cancer, with recurrent or refractory disease
      after the initial chemotherapy. TXL was administered at escalating concentrations
      up to 60-100 mg/m(2), while the dose of CBDCA was fixed at an AUC of 2. In regard
      to the dosing schedule, premedication was performed as defined before TXL
      administration, and TXL and CBDCA were administered, in that order, by
      intravenous infusion for over at least 1 hour. The 4-week period, including the
      administration of both drugs on Day 1, 8, and 15, was regarded as one course of
      treatment. No cases developed grade 4 hematoxicity, but leukopenia and
      neutropenia occurred. All cases of leukopenia of step 4 and step 5 developed
      grade 3 leukopenia. Grade 2 thrombocytopenia was one example at a low rate. Non
      hematological toxicity included neuropathy, arthralgia and muscle pain, but none
      of the patients developed grade 3 or 4. The response rate was 41.7% (5/12). The
      response rate of cases administered over TXL 80 mg was 66.7% (4/6). Based on
      these results,the following dose schedule was recommended for planning and
      designing a phase II study in the future: CBDCA AUC 2+TXL 80 mg/m(2) (Days 1, 8,
      and 15 q 4 weeks).

PMID- 17033236
TI  - [Case report of advanced breast cancer responding to capecitabine and trastuzumab
      combination therapy].
AB  - We conducted a concomitant administration of capecitabine (2,400 mg/day for 21
      days followed by a 7-day interval) and trastuzumab (2 mg/kg weekly) to a 73-year
      old female patient with impaired lower limb function diagnosed with bilateral
      breast cancer. The patient had a complete response (CR) to pulmonary metastases,
      and carcinoembryonic antigen (CEA) level had normalized from 46.4 ng/ml to 0.6
      ng/ml. Left mastectomy was performed in order to control bleeding from tumors. No
      adverse events attributable to medication were observed. The concomitant
      administration of capecitabine and trastuzumab is a promising therapy with the
      potential to greatly improve patient quality of life (QOL).

PMID- 17033237
TI  - [A case of advanced gastric cancer with long-term survival treated by
      chemotherapy and surgical cytoreduction].
AB  - A 74-year-old man was revealed to have type 3 gastric cancer with lymph-node
      metastasis in the third group (N 3) and liver metastasis (H 1). Since we regarded
      a curative operation as impossible, we started preoperative chemotherapy using TS
      1 plus irinotecan hydrochloride (CPT-11) on the premise that we would perform
      surgical cytoreduction after the chemotherapy. After two courses of chemotherapy,
      both the primary lesion and the liver metastasis were reduced in size, and the
      paraaortic lymph-nodes disappeared. Subsequently, a distal gastrectomy (D 0,
      curability C) was performed. The patient has been receiving postoperative
      chemotherapy using TS-1 and paclitaxel as an outpatient for 2.3 years. Although
      there is not enough evidence to support the benefit of surgical cytoreduction,
      chemotherapy combined with surgical cytoreduction would improve the survival time
      without deterioration of quality of life (QOL) in patients with advanced gastric
      cancer. This combined therapy should be considered as one of the promising
      strategies for advanced gastric cancer.

PMID- 17033238
TI  - [A case of advanced gastric cancer--efficacy of combination therapy of
      doxifluridine and weekly paclitaxel].
AB  - A 65-year-old man underwent distal gastrectomy for advanced gastric cancer.
      Histological examination revealed that a lymph node metastasis extended to the
      para-aortic nodes. After operation, he was treated with TS-1 as first-line
      chemotherapy. After 10 months of the first-line chemotherapy, the lymph node
      swelling increased in size, and new lesions were detected. Then, the patient was
      treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly
      paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and
      oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were
      performed as the second-line chemotherapy. After 2 courses, abdominal CT scan
      showed a remarkable reduction of the para-aortic lymph nodes. The second-line
      chemotherapy was continued until the 7th course, then stopped without progression
      of the disease, and the patient maintained good quality of life. PTX/5'-DFUR
      combination therapy was thought to be an effective chemotherapy for advanced
      gastric cancer.

PMID- 17033239
TI  - [A resected case of advanced gastric cancer with multiple liver metastasis
      responding to preoperative TS-1/CDDP chemotherapy].
AB  - CASE: A 75-year-old man was admitted to our hospital with hematoemesis.
      Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the
      lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We
      thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed.
      TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by
      intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week
      period as the first course. After the third course, the primary lesion and the
      liver metastasis showed a partial response in terms of size. No serious drug
      adverse reaction was observed. Since there was no longer any reduction of the
      tumor, gastrectomy and coagulation therapy for liver metastasis were performed,
      and he has been alive for 15 months without recurrence. Combined use of TS-1 and
      CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.

PMID- 17033240
TI  - [Two metastatic colonic cancer patients successfully treated by combination
      therapy of tegafur/uracil (UFT) and oral Leucovorin].
AB  - Two metastatic colonic cancer patients were successfully treated by the
      combination therapy of UFT plus oral Leucovorin (UFT/LV). UFT was administered
      orally every eight hours at a dose of 300 mg/day in case of less than 1.20 m(2),
      400 mg/day in case of between 1.20 and 1.70 m(2), 500 mg/day in case of over 1.70
      m(2), and Leucovorin (75 mg/day) was simultaneously given for 28 consecutive days
      and stopped for seven days. This cycle was repeated until the patients requested
      the therapy be discontinued or a severe adverse reaction was observed. Case 1: A
      79-year-old male had undergone sigmoidectomy for colonic cancer in 2001 and was
      diagnosed with pulmonary metastases in August, 2005. His performance status (PS)
      was grade 3. Case 2: A 61-year-old male with liver metastasis whose primary
      colonic lesion was surgically resected. After 2 cycles of UFT/LV therapy, a good
      partial response was achieved in both cases. Adverse effects were very mild,
      indicating that this therapy was very safe and recommendable for the treatment of
      metastatic colonic cancer patients with poor PS.

PMID- 17033241
TI  - [A case of effective multidisciplinary treatment with hepatic resection for
      synchronous multiple liver metastases from rectal cancer].
AB  - A 56-year-old-man complained of abdominal pain, and was diagnosed as having
      advanced rectal cancer with synchronous multiple metastatic liver cancer (H 3) in
      July 1999. He underwent low anterior resection and hepatic partial resection (S
      1, S 2+S 3, S 5, S 6, S 8) in August 1999. In addition, he underwent hepatic
      arterial infusion chemotherapy (HAI) 6 times at ADM 30 mg+5-FU 1,000 mg+MMC 16 mg
      between October 1999 and July 2000 for recurrent metastatic liver cancer. He has
      survived more than 6 years after the initial surgery. Multidisciplinary treatment
      with hepatic resection may well be a strategy for patients with multiple
      colorectal liver cancer, even though H 3 type of metastasis.

PMID- 17033242
TI  - [A case of advanced rectal cancer responding to oral UFT and Leucovorin-based
      preoperative chemoradiation therapy].
AB  - We report a case of a 44-year-old male with advanced lower rectal cancer that
      showed a significant effect after preoperative chemoradiation therapy.
      Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy
      in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered
      daily for 4 weeks. Consequently, the patient underwent a total pelvic
      exenteration with lymph node dissection (D 3). Histopathological findings showed:
      invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade
      2. Preoperative chemoradiation therapy appears to be effective for locally
      advanced lower rectal cancer.

PMID- 17033243
TI  - [Case report of a liver metastasis from rectal cancer achieving complete response
      (CR) by a combination of intra-hepatic arterial infusion of irinotecan (CPT-11)
      with degradable starch microspheres (DSM) and weekly high-dose intra-hepatic
      arterial chemotherapy with 5-FU].
AB  - A 67-year-old woman, who was diagnosed with rectal cancer and liver metastasis,
      underwent a low anterior resection of the rectum in May 2004. Two months later,
      the level of tumor markers increased and a CT scan revealed a 45 x 35 mm liver
      metastasis in the S(8) segment. She was referred to our hospital for treatment of
      the liver tumor. Intra-hepatic arterial infusion of irinotecan (CPT-11) and
      mitomycin C (MMC) with degradable starch microspheres (DSM) was given in July
      2004. Following this, a 34-week course of weekly high-dose intra-hepatic arterial
      5-FU infusion (5-FU 1,000 mg/m(2)) was performed. In April 2005, the size of the
      liver metastasis decreased, and the level of serum tumor marker normalized. A CT
      and echo scan revealed a calcified tumor, and therefore all chemotherapy was
      stopped. She was followed in the outpatient clinic, with no evidence of
      recurrence for 12 months. This case suggests that the use of intra-hepatic
      arterial infusion of CPT-11 and MMC with DSM is useful for the treatment of liver
      metastases in colorectal cancer.

PMID- 17033244
TI  - [A case of adenocarcinoma of unknown primary site successfully treated with
      gemcitabine monotherapy].
AB  - A 68-year-old female diagnosed with adenocarcinoma of unknown primary site (ACUP)
      by biopsy of supraclavicular lymph node was admitted to our department because of
      progressive dyspnea with cough. The diagnosis of multiple lung metastases and
      malignant pleural effusion was made. Marked elevation of serum CA 19-9 and DUPAN
      2 urged us to treat her as a case of pancreatic carcinoma. Gemcitabine
      monotherapy yielded resolution of symptoms, decline in the level of tumor
      markers, shrinkage of lung metastases, and disappearance of pleural effusion.
      After 10 cycles, the chemotherapy was terminated. However, clinical deterioration
      was observed two months later. The re-treatment with gemcitabine was started, and
      a good response was obtained again. Gemcitabine monotherapy can be one of the
      treatment options for ACUP.

PMID- 17033245
TI  - [A case of squamous cell carcinoma of unknown primary site with involvement of
      cervico-mediastinal lymph nodes successfully treated by chemoradiotherapy].
AB  - A 70-year-old woman was admitted with cervicomediastinal lymph node metastases
      from squamous cell carcinoma of unknown primary site (Sq-CUPS). The patient was
      treated with 4 cycles of chemotherapy combining carboplatin and paclitaxel with
      subsequent radiation therapy. After serial treatment, a partial response was
      obtained, and the disease has not recurred for over 2 years. Chemotherapy with
      carboplatin and paclitaxel followed by sequential radiation therapy was suggested
      to be potentially useful for Sq-CUPS with involvement of cervicomediastinal lymph
      nodes, although this group of patients is generally regarded to have a poor
      prognosis.

PMID- 17033246
TI  - [Colonic perforation in a patient treated with combination chemotherapy for
      recurrent ovarian clear cell adenocarcinoma].
AB  - BACKGROUND: Colonic perforation due to colitis is a known and reported side
      effect of chemotherapy. CASE REPORT: A 53-year-old woman was treated with
      combination chemotherapy of irinotecan plus cisplatin for a recurrent ovarian
      clear cell adenocarcinoma. Steroid was also used for suspected interstitial
      pneumonia. After two cycles of treatment, she developed a colonic perforation.
      Emergency laparotomy was not performed because of poor performance status with
      multiple lung metastases, pleural effusion and pericardial effusion. Colonoscopy
      showed a perforated wall at the cecum, and a long tube with balloon was inserted
      for occlusion. In addition, a peritoneal drainage tube was inserted. Oral intake
      could be restarted for a while, but she died from tumor progression one and a
      half months after the diagnosis of perforation. CONCLUSION: Non-surgical
      management with peritoneal drainage and ileus tube was useful in this case of
      colonic perforation for preserving oral intake and quality of life.

PMID- 17033247
TI  - [A case of stage IVA intrahepatic biliary tract cancer successfully treated with
      gemcitabine].
AB  - We reported a case of non-resectable intrahepatic biliary tract cancer, treated
      with Gemcitabine and oral anticancer drugs. A 45-year-old man was admitted to the
      hospital due to abdominal distension and fatigue. CT scan revealed intrahepatic
      biliary tract cancer in the left lobe, which had metastasized to both lobes.
      Based on the diagnosis of non-resectable intrahepatic biliary tract cancer,
      systemic chemotherapy using gemcitabine (GEM) was employed. One course of the
      treatment consisted of 4 weeks. GEM 1,000 mg was administered once a week for 3
      weeks followed by a week of no treatment. At the same time, the oral anti-cancer
      drug (5'-DFUR 600 mg/day) was administered every day. After 4 courses of
      chemotherapy, both the primary tumor and the hepatic metastasis were diminished,
      and the serum level of CA19-9 was reduced to the normal value. Relief from the
      abdominal distension allowed the patient to return to work. The chemotherapy was
      continued by outpatient-clinic treatment, preserving the quality of life for 13
      months. The present case shows that gemcitabine/5'-DFUR combination is well
      supported in advanced unresectable biliary tract cancer.

PMID- 17033248
TI  - [Two cases of advanced pancreatic cancer with cervical lymph node or liver
      metastasis responding well to S-1 monotherapy].
AB  - In two patients with advanced pancreatic cancer with cervical lymph node or liver
      metastasis and no indication of pancreatic resection and radiotherapy, oral
      treatment with S-1 (an anti-cancer agent of fluoropyrimidine derivative) exerted
      high anti-tumor activity on the metastatic lesions. Both cases responded well to
      this therapy in the late phase II study of S-1 in patients with advanced
      pancreatic cancer designed to evaluate efficacy and safety. In Case 1 (with
      cervical lymph node metastasis), the anti-tumor efficacy of this therapy was
      evaluated as a partial response (PR) after the first four courses of treatment.
      In Case 2 (with liver metastasis), the efficacy was evaluated as PR for overall
      response. Thus, the therapy indicated excellent efficacy in both cases. No grade
      3 or severe adverse event was noted in either of the two cases. In Case 1, grade
      2 anemia, stomatitis, vomiting and fatigue, and some other mild events were
      noted. When used as a systemic chemotherapy for metastatic pancreatic cancer,
      oral treatment of S-1 is highly effective, tolerable and convenient in an
      outpatient clinic. This drug is a promising way to improve and preserve the QOL
      essential to long-term home care.

PMID- 17033249
TI  - [Resolution of liver metastases in response to S-1 monotherapy in advanced
      pancreatic cancer--a case report].
AB  - We report a case in a late phase II clinical study investigating the efficacy and
      safety of the oral fluoropyrimidine anticancer drug S-1. The drug proved
      effective in a patient with inoperable advanced pancreatic cancer in whom
      radiation therapy was not indicated. The antitumor effect after 4 courses was
      rated excellent, with a target site (liver) evaluation of CR and overall
      evaluation of PR. In particular, two liver metastases, measuring 18.7 x 15.4 mm
      and 16.2 x 14.6 mm, respectively, both resolved, and S-1 was found to exert a
      potent antitumor effect against metastases. Assessment of adverse events revealed
      no grade 3 or 4 adverse reactions, and other adverse events were all mild. Based
      on the above results, S-1 appeared to be effective against advanced pancreatic
      cancer and showed excellent tolerability.

PMID- 17033250
TI  - [Two patients effectively treated by S-1 monotherapy for metastatic pancreatic
      cancer].
AB  - We report two metastatic pancreatic cancer patients who showed marked tumor
      shrinkage following administration of the oral fluorinated pyrimidine anticancer
      drug, S-1. In the early phase II trial of S-1 for metastatic pancreatic cancer,
      both patients showed a partial response (Japan Society for Cancer Therapy
      Criteria): the reduction ratio of the tumor volume was 81.4% in the patient with
      liver metastasis (Case 1) and 86.9% in the patient with lung metastasis (Case 2).
      Case 1 showed grade 3 anorexia and decrease of the serum hemoglobin as severe
      adverse effects, but the other adverse reactions were mild. Both patients could
      be treated as outpatients. S-1 showed a promising antitumor effect and
      tolerability in patients with metastatic pancreatic cancer, and it was also
      considered to be beneficial for patients in terms of convenience of
      administration, that is, by the oral route.

PMID- 17033251
TI  - [Chemotherapy-naive advanced pancreatic cancer with multiple liver metastases
      successfully treated by S-1 monotherapy--a case report].
AB  - We report a patient with chemotherapy-naive advanced pancreatic cancer having
      multiple liver metastases which dramatically responded to S-1, an oral
      fluoropyrimidine. The patient was enrolled in the "Late Phase II Clinical Study
      of S-1 in Patients with Advanced Pancreatic Cancer." Anti-tumor efficacy after
      the first four courses of S-1 monotherapy was confirmed to be partial response
      (PR) in overall response by Response Evaluation Criteria in Solid Tumors
      (RECIST). Grade 3 neutropenia was observed, but no other severe toxicities were
      noted. On the basis of the results of the late phase II clinical study, S-1 is a
      promising agent for systemic chemotherapy against advanced pancreatic cancers
      because of its excellent efficacy, high tolerability, and convenient route of
      oral administration.

PMID- 17033252
TI  - [Examination of the safety of docetaxel/cyclophosphamide combination therapy for
      advanced recurrent breast cancer].
AB  - In the treatment of recurrent breast cancer in patients previously treated with
      anthracycline drugs, taxane drugs are generally used. This time, we
      retrospectively studied the safety of docetaxel/cyclophosphamide combination
      therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8
      years old) were included in the study. Metastatic/recurrent sites included 3
      skin, 2 each of contralateral breast, lung and bone, and 1 each of liver,
      carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a
      history of anthracycline treatment. The patients received TC at doses of 60
      mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse
      events, non-hematotoxic events included alopecia in all the patients, generalized
      malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3
      decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia
      associated with oral candida. The patient was admitted and treated with fluid
      replacement and granulocyte colony-stimulating factor (G-CSF). There were no
      other patients in whom the treatment was prolonged or dosage was reduced due to
      adverse reactions. TC therapy is considered to be a beneficial treatment method
      in terms of safety since it can be instituted on an outpatient basis.

PMID- 17033253
TI  - Central obestatin administration does not modify either spontaneous or ghrelin
      induced food intake in rats.
AB  - The isolation of ghrelin unveiled a new system implicated in food intake
      regulation. The recently isolated hormone obestatin derives from the same
      precursor of ghrelin and seems to perform opposite actions. It could be part of a
      dual system connecting gut and brain to regulate energy homeostasis. The ability
      of intracerebroventricular administration of obestatin to modify food intake was
      evaluated. Obestatin had no effect on spontaneous food intake in both ad libitum
      and food restricted rats. The obestatin injection was not able to antagonize the
      ghrelin-stimulated increase in food intake either. In conclusion, the present
      work does not support a role for obestatin on the regulation of food intake in
      any model studied.

PMID- 17033254
TI  - Obestatin inhibits feeding but does not modulate GH and corticosterone secretion
      in the rat.
AB  - Obestatin is a recently discovered 23 amino acids peptide derived from the
      ghrelin gene. As opposed to ghrelin, obestatin was shown to inhibit food intake
      in mice. The aims of this research were to study the effects of acute obestatin
      treatment on feeding behavior in the rat and its effects on GH and corticosterone
      secretion. Our results demonstrate that in young-adult male rats, obestatin
      effectively blunts the hunger caused by short-term starvation. Obestatin did not
      modify GH secretion in 10-day-old rats and did not antagonize the GH-releasing
      effects of hexarelin. Moreover, obestatin administration had no effects on
      spontaneous corticosterone secretion. In conclusion, these data demonstrate that
      in young-adult male rats the newly discovered obestatin can inhibit feeding but
      does not modify GH and corticosterone release in infant rats.

PMID- 17033255
TI  - Endogenous hyperinsulinemic hypoglycemia: diagnostic strategies, predictive
      features of malignancy and long-term survival.
AB  - Diagnostic strategies, malignancy predictors and long-term survival were
      retrospectively evaluated in patients with hyperinsulinemic hypoglycemia (64
      insulinomas). Lower median glycemia was 30 (range 20-53) mg/dl [1.6 (1.1-2.9)
      mmol/l] with concurrent insulin of 48 (13.2-217) microU/ml and 15 (2-46)
      microU/ml measured by radioimmunoassay (RIA) and immunofluorimetric assay (IFMA),
      respectively. All patients with insulinomas had a positive prolonged fast within
      48 h. Sensitivity of localization methods was: ultrasonography (US) 23%, computed
      tomography (CT) 28%, magnetic resonance imaging (MRI) 65%, endoscopic US 75%,
      arteriography 38%, portal venous sampling 67%, selective arterial calcium
      stimulation 67%, intraoperative US 94% and palpation 92%. Nine patients (14%) had
      malignant insulinomas. Age at diagnosis (mean+/-SD, 53.8+/-19 vs 39.4+/-16.3 yr;
      p=0.03), insulin (1372+/-730 vs 785+/-659% (percentage of the method's diagnostic
      cut-off; 6 and 3 microU/ml for RIA and IFMA, respectively; p=0.007) and C-peptide
      levels (9.8+/-2.9 vs 3.9+/-2.8 ng/ml (3.2+/-0.9 vs 1.3+/-0.9 nmol/l; p=0.006),
      and tumor size (6.2+/-4.1 vs 1.5+/-0.6 cm; p=0.0002) were increased in malignant
      insulinomas. C-peptide level above 6.1 ng/ml (2.0 nmol/l) had a 100% sensitivity
      and 96% specificity, and tumor size above 2.6 cm yielded a sensitivity of 88% and
      specificity of 100% in predicting malignancy. Survival of patients with malignant
      insulinomas was significantly impaired (16 vs 100% at 5 yr; p=0.0000001). The
      diagnosis of insulinoma can be made within 48 h of fasting. The association
      between intraoperative US and palpation evidenced the tumor in 95% of the
      patients. C-peptide and tumor size were reliable malignancy predictors.

PMID- 17033256
TI  - Endogenous coenzyme A glutathione disulfide in human myocardial tissue.
AB  - Besides its role as a mechanical pump, the human heart serves as an endocrine
      organ, where known and as yet unknown hormones are produced. It is very likely
      that these hormones play an important role in cardiovascular regulation. In this
      study, a new endogenous vasoactive substance, coenzyme A glutathione disulfide
      (CoASSG), was isolated and identified in myocardial tissue. Human myocardial
      tissue was extracted with perchloric acid and fractionated by size exclusion-,
      displacement-, anion-exchange- and reversed-phase chromatography. In one fraction
      purified to homogeneity, CoASSG was identified by matrix assisted laser
      desorption/ionization (MALDI) mass-spectrometry, post-source decay MALDI-mass
      spectrometry and enzymatic structure analysis. Furthermore, CoASSG was also
      isolated from human cardiac specific granules. CoASSG has potent vasoconstrictive
      and proliferative effects. Therefore, CoASSG may affect myocardial function as an
      endocrine or autocrine substance after being released from myocardial specific
      granules.

PMID- 17033257
TI  - Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as
      compared to subacute thyroiditis.
AB  - BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist:
      type 1 AIT is a condition of true hyperthyroidism developing in patients with pre
      existing thyroid disorders, and usually requires thyroid ablative treatment. On
      the other hand, type 2 AIT is a form of destructive thyroiditis occurring in
      normal thyroids, the management of which usually consists in glucocorticoid
      treatment. AIM: To assess the long-term outcome of thyroid function in a
      prospective study of type 2 AIT patients, as compared to patients with De
      Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive
      patients with type 2 AIT were evaluated during oral glucocorticoid treatment
      (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month
      period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive
      patients with SAT, referred to our Institutes during the same period and treated
      with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT
      patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1
      vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3)
      concentrations at diagnosis were increased in both conditions, but higher in type
      2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001;
      FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of
      thyrotoxicosis was obtained in all patients in both groups, but restoration of
      euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT
      patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid
      after glucocorticoid withdrawal and required levothyroxine replacement.
      CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent
      hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of
      thyroid status is required after type 2 AIT.

PMID- 17033258
TI  - Reduced levels of adiponectin in sleep apnea syndrome.
AB  - BACKGROUND: To investigate adiponectin levels in an obese population with and
      without obstructive sleep apnea syndrome (OSAS) and the acute modifications in
      adiponectin after a whole-night control by auto continuous positive air pressure
      (CPAP). METHODS: 46 obese subjects [22 males, 24 females, age 55.1+/-11.4 yr,
      body mass index (BMI) 38.9+/-6.5 kg/m2]: 11 OSAS with apnea/hypopnea index (AHI)
      from 10/h to 30/h, 14 OSAS with AHI >30/h and 21 without OSAS. Thirty-seven
      normal weight healthy subjects (20 males, 17 females, age 31.3+/-9.5 yr, BMI
      21.5+/-1.8 kg/m2). Serum adiponectin levels, biochemical parameters,
      anthropometric measurements, pulmonary function, pulse-oxymetry and
      polisomnography. RESULTS: The 3 groups of obese patients were comparable for
      gender, BMI, age, fat mass, fat free mass, hip and waist circumference, waist-to
      hip ratio (WHR), systolic and diastolic blood pressure and glycometabolic
      parameters. Adiponectin levels were significantly reduced in obese patients
      compared to healthy normal weight subjects (8.1+/-3.5 vs 11.3+/-4.8 microg/ml
      p<0.001) In particular, adiponectin showed a trend to decrease according to the
      severity of OSAS. No differences in adiponectin levels were found after a whole
      night control by Auto CPAP. CONCLUSIONS: OSAS is associated with reduced levels
      of adiponectin independently of insulin-resistance and BMI. These low adiponectin
      levels may contribute to the increased mortality seen in such patients.

PMID- 17033259
TI  - Hormonal control of inhibin B in men.
AB  - Serum inhibin B (IB) and testosterone (T) levels, secreted by Sertoli cells (SC)
      and Leydig cells (LC), respectively, are parameters of the functional state of
      these cells. Whereas LC activity and, consequently, T secretion are regulated by
      serum LH, factors regulating IB secretion by SC are still partially unknown.
      There is evidence that under certain conditions such as puberty, aging or some
      spermatogenesis defects, LH levels or Gn-independent factors might contribute to
      regulating SC activity and IB secretion. Among these factors, GH and IGF-I as
      well as PRL might have a role. Therefore, in order to explore the possible
      effects of either LH alone and FSH alone or a combination of both Gn,
      respectively, on SC function, IB plasma levels and spermatogenesis, we studied
      their effects in 6 patients with hypogonadotropic hypogonadism (HH), whereas the
      effects of GH on these parameters were studied in 6 men with panhypopituitarism
      (PH). Finally, the possible effects of PRL on SC function and spermatogenesis
      were studied in 6 patients with hyperprolactinemia (HPRL); 24 normal, fertile
      adults served as control group. In men with HH, neither human chorionic Gn (hCG)
      nor FSH, respectively, were able to increase serum IB after 3 months of therapy,
      whereas combined Gn therapy for 24 months increased IB plasma levels and
      stimulated spermatogenesis in 4 out of 6 hypogonadal men. In panhypopituitaric
      men, GH added to the classical Gn therapy did not have an additional effect on
      serum IB levels or spermatogenesis. Surprisingly, in our hyperprolactemic men, IB
      plasma levels were increased and positively correlated (p<0.01) with serum PRL
      levels, whereas normalization of the latter by cabergoline treatment caused a
      decrease of IB levels and a moderate increase in T, LH and FSH. In conclusion,
      the lack of SC response to FSH therapy alone, as opposed to the response to
      combined Gn therapy, might indicate that normalization of serum T by hCG is
      required to obtain IB secretion by SC. Addition of GH did not affect SC function,
      serum IB levels or spermatogenesis. Finally, our data suggest that PRL plasma
      levels might have a direct role on IB secretion, suggesting that the hypogonadism
      found in patients with HPRL might be a consequence of both central (inhibition of
      Gn secretion) and peripheral (stimulation of IB secretion) origin.

PMID- 17033260
TI  - Iodine deficiency and goiter prevalence in Turkey after mandatory iodization.
AB  - OBJECTIVE: The determination of (a) iodine deficiency, and (b) the relation
      between the iodized salt consumption in the Isparta province of Turkey. METHODS:
      Five hundred students between 6-11 yr of age were evaluated. With a
      questionnaire, the subjects were asked whether they were using iodine-containing
      salt or not. After their body weight and height were measured, thyroid glands
      were examined with palpation, thyroid volumes were determined with
      ultrasonography (USG), and urinary iodine concentration was analyzed. RESULTS:
      The median urinary iodine concentration (UIC) of children was 7.00 microg/dl.
      This value reveals that Isparta is a region with mild iodine deficiency. The
      total goiter prevalence was 30.4% with palpation and 26% with USG. The goiter
      prevalence by ultrasonography was 14.2% for the urban and 36.2% for the rural
      areas. This difference was statistically significant (p<0.05). The rate of total
      iodized salt consumption was 68%, which was not a satisfactory level. The
      consumption of iodized salt in the urban areas was significantly higher than that
      in rural areas (74 vs 62%, p<0.05). The median UIC value was 10.00 microg/dl in
      urban areas compared to 5.00 microg/dl in rural areas. CONCLUSIONS: Our results
      indicate that although Isparta is a region with mild iodine deficiency, goiter
      prevalence remains a serious problem.

PMID- 17033261
TI  - Intra-follicular leptin concentration as a predictive factor for in vitro oocyte
      fertilization in assisted reproductive techniques.
AB  - BACKGROUND: Granulosa-cells are able to produce and store leptin, suggesting that
      this hormone is locally involved in the regulation of follicular growth. In this
      study, the role of follicular fluid (FF) leptin concentration in predicting
      oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic
      women undergoing controlled ovarian stimulation (COS) for assisted reproductive
      techniques. MATERIALS AND METHODS: Leptin concentration was measured in 47
      consecutively collected FF in which a mature oocyte had been found during the
      ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality
      scoring systems. RESULTS: Mean leptin concentration was significantly higher in
      FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no
      evidence of fertilization (no. 22) at the 16-18 h check (26.0+/-6.1 vs 15.3+/
      10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the
      two groups (21.4+/-3.4 and 21.0+/-5.1 mm, respectively). Logistic regression
      analysis identified FF leptin levels as the best predictive parameter for oocyte
      fertilization (p<0.001). When receiving operating characteristics curve was
      employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off
      in predicting fertilization of oocytes. FF with leptin concentrations higher than
      this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF
      levels < or =20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05).
      No correlation emerged between FF leptin and the score attributed to 15 valuable
      embryos at the zygote stage (r=-0.01) and at 48 h after insemination (r=0.1).
      CONCLUSIONS: FF leptin levels are a better predictor of oocyte fertilization
      success rates than follicular diameter. These results underline the relevance of
      FF variables in developing methods for oocyte selection.

PMID- 17033262
TI  - Saliva cortisol measurement: simple and reliable assessment of the glucocorticoid
      replacement therapy in Addison's disease.
AB  - No ideal parameter is available for assessment of the glucocorticoid replacement
      therapy in Addison's disease. Serum cortisol day-curves can be used to monitor
      the therapy, but this technique is cumbersome and expensive. We evaluated the
      potential for saliva cortisol measurement in this setting. We found excellent
      correlation between serum and saliva cortisol after oral intake of cortisone
      acetate (no. 7) or iv administration of hydrocortisone (no. 4) (Pearson's R=0.83
      0.98, p<0.002). A morning dose of 12.5 mg cortisone acetate yielded wide
      interindividual variations in cortisol levels in saliva. Saliva cortisol
      measurements were successfully adopted to evaluate and adjust doses in
      outpatients. We conclude that cortisol measurement in saliva is practical and
      reliable, and is preferable to serum cortisol measurement in the assessment of
      the glucocorticoid replacement therapy. Our results confirm that only a minority
      of patients require more than 12.5 mg of cortisone acetate (equivalent to 10 mg
      hydrocortisone) in the morning to have sufficient cortisol levels during the
      first part of the day.

PMID- 17033264
TI  - Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in
      pregnancy.
AB  - The association of pheochromocytoma (PHEO) and pregnancy is uncommon and life
      threatening for both the fetus and the mother. Early diagnosis and treatment is
      essential to decrease maternal and fetal mortality and to differentiate the
      disease from the more common pre-eclampsia. While medical treatment should be
      started immediately after diagnosis, the timing of surgical treatment is still
      debated. We describe the case of a 27-yr-old woman in the 18th week of pregnancy
      who showed a biochemical pattern typical of PHEO and, by imaging studies, 2
      tumors with the same characteristics: the first localized on the right adrenal
      gland, the second at the right renal hilum. The patient underwent surgery because
      of suspicion of malignant PHEO with local metastasis, while histology revealed a
      rare association of a solitary PHEO and para-aortic neurofibroma, both tumors
      embryologically deriving from a common cell precursor.

PMID- 17033263
TI  - Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood
      onset GH deficiency: a proposal of the Italian Society for Pediatric
      Endocrinology and Diabetes (SIEDP/ISPED).
AB  - The diagnosis of GH deficiency (GHD) is based on the measurement of peak GH
      responses to pharmacological stimuli. Pharmacological stimuli, however, lack
      precision, accuracy, are not reproducible, are invasive, non-physiological and
      some may even be hazardous. Furthermore, different GH commercial assays used to
      measure GH in serum yield results that may differ considerably. In contrast to
      GH, IGF-I can be measured on a single, randomly-obtained blood sample. A review
      of the available data indicates that IGF-I measurement in the diagnosis of
      childhood-onset isolated GHD has a specificity of up to 100%, with a sensitivity
      ranging from about 70 to 90%. We suggest an algorithm in which circulating levels
      of IGF-I together with the evaluation of auxological data, such as growth rate
      and growth, may be used to assess the likelihood of GHD in pre-pubertal children.

PMID- 17033265
TI  - Polycythemia as the first manifestation of Cushing's disease.
AB  - A 39-yr-old man presented to our hospital with unexplained erythrocytosis and
      hypertension. His follow-up for erythrocytosis had begun 2 yr earlier in another
      hospital and he had been diagnosed with polycythemia rubra vera. On admission to
      our hospital he was hypertensive (165/95 mmHg) and, except for the presence of
      moon-like face and facial plethora, his physical examination was normal. His
      hemoglobin concentration was 19.2 g/dl, and hematocrit was 58.9% with an
      increased red blood cell mass of 58 ml/kg as measured by radioisotope (Cr51).
      Blood film, other hematological indices except for elevated leukocyte alkaline
      phosphatase score, arterial gas analysis, and examination of aspirated bone
      marrow were all normal. An abdominal ultrasonography showed no evidence of
      splenomegaly. A diagnosis of probable secondary erythrocytosis was made. Early
      morning serum cortisol and 24-h urinary free cortisol concentration as well as
      serum ACTH were high. Serum cortisol was not suppressed by low-dose
      dexamethasone, but suppressed by high-dose dexamethasone. Pituitary magnetic
      resonance imaging showed no lesion. After inferior petrosal sinus sampling
      suggesting right-central ACTH secretion, the patient underwent transnasal
      transsphenoidal pituitary adenomectomy. Both hypercortisolemia and erythrocytosis
      regressed completely after the adenomectomy. After the operation, the patient's
      hemoglobin concentration and hematocrit decreased steadily, and 1 month post
      adenomectomy his hemoglobin is 14.9 g/dl and hematocrit 44.8%. Thus, Cushing's
      syndrome should be a routine part of evaluation of unexplained polycythemia.

PMID- 17033266
TI  - Acromegaly and end-stage renal disease: a diagnostic challenge.
AB  - Chronic renal failure is associated with an impairment of the GH/IGF-I axis. We
      report the diagnostic challenges in a 72-yr-old female suffering from end-stage
      renal disease and presenting with clinical findings suggestive of acromegaly. GH
      was not suppressed during an oral glucose tolerance test, but rose paradoxically.
      However, serum IGF-I levels were within the normal range. IGF-binding proteins
      (IGFBP)-2 and -3 were markedly elevated and GH-binding protein (GHBP) was
      diminished. Clinical findings suspicious of acromegaly could be ascribed to pre
      existing characteristics and consequences of end-stage renal disease. This
      suggested that the disturbances of the GH/IGF-I axis in our patient were due to
      chronic renal disease, rather than acromegaly. In the work-up for acromegaly,
      clinicians should be alerted to GH resistance in chronic renal failure.

PMID- 17033267
TI  - Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.
AB  - Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH), although few cases have so far been reported. We
      described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary
      macroadenoma. He had a recent history of two syncopal attacks which had occurred
      in the last two months. Baseline assessment demonstrated a sodium serum level of
      114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal
      function testing did not show any abnormality. Plasma and urinary osmolality (238
      and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH.
      Accordingly, 3% hypertonic saline solution was started, followed by water intake
      restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of
      the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess.
      Because the nature of the lesion appeared uncertain, antibiotic therapy was
      initiated. After one month, a new CT scan did not show any evidence of the
      mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and
      remained stable thereafter, without fluid restriction. This case very well
      demonstrates that, in the presence of hyponatremia due to SIADH, more frequently
      associated co-morbidities (ie mediastinic diseases) have to be searched, even in
      the presence of a possible, yet rare, cause of this syndrome (ie pituitary
      adenoma).

PMID- 17033269
TI  - The importance of investigation of pituitary function in children and adolescents
      following traumatic brain injury.
AB  - It is now widely accepted that brain injuries are often the cause of acquired
      hypopituitarism in adulthood. The information about the pituitary function in
      brain-injured children and adolescence is however scanty. An international
      workshop entitled "Traumatic brain injury and hypopituitarism" was held on 9-10
      April 2006 in Granada, Spain, in order to explore the relatively unknown but
      potentially important field of investigation, diagnosis and treatment of
      pituitary deficiency in children and adolescents following traumatic brain injury
      (TBI). The following conclusions were reached: 1) a prospective pediatric and
      adolescent study of pituitary function was indicated; 2) close collaboration
      among neurosurgeons, neurologists, rehabilitation specialists and pediatric
      endocrinologists, with support from adult endocrinologists, is essential to
      achieve a coordinated approach to the care of children after TBI; 3) a model of
      interaction, similar to that now existing with oncologists, needs to be
      established; 4) a "pediatric TBI late-effects" service should be created,
      preferably led by endocrinologists, so that knowledge of growth and puberty can
      be included, in order to optimize identification, investigation and treatment of
      this important group of patients.

PMID- 17033268
TI  - Diabetic microangiopathy: IGFBP control endothelial cell growth by a common
      mechanism in spite of their species specificity and tissue peculiarity.
AB  - Endothelial cells (EC) play a role in many diseases including diabetes mellitus.
      EC share common functions, such as angiogenesis and vascular remodeling both
      regulated by proliferation and apoptosis, anti-thrombotic properties, regulation
      of vascular tone, control in the passage of nutrients and secretion of peptides
      and growth factors. However, EC are characterized by site-specificity so their
      characteristics depend on the organs and tissues where they are. The IGF system
      induces important growth factors that control cell growth in different
      microvascular EC (mEC). This family includes IGF-I and IGF-II peptides, their
      receptors and regulatory proteins IGF-binding proteins (IGFBP-1 to IGFBP-6). The
      IGFBP modulate their interaction with the IGF membrane receptors and might be
      regulated at a transcriptional and post-transcriptional level, thus determining
      the biological IGF-dependent effects on target cells. The IGF system is also a
      mediator of vascular diseases, and its altered balance might contribute to
      endothelial dysfunction with the development and evolution of diabetic
      microangiopathy. We reported here the reviewed literature of IGFBP production
      from various sources of mEC, showing that they predominantly express IGFBP-2
      through IGFBP-5 mRNA. The different pattern of IGFBP secretion depends on the
      anatomical district and on the species of the tissues. Nevertheless, based on our
      and other experimental observations, we suggested that a common mechanism of
      IGFBP regulation in mEC could be hypothized. In retinal and glomerular EC the
      IGFBP4/IGFBP5 ratio controls the response of these cells to IGF-I and high levels
      of glucose, in terms of cellular growth.

PMID- 17033270
TI  - Assessing the relationship between antigenicity and immunogenicity of human
      rabies vaccines. Results of a meta-analysis.
AB  - A meta-analysis was done to study the relationship between antigenecity and
      immunogenecity of human rabies vaccines. The data of ten cell culture human
      rabies vaccine studies conducted at a single centre during 1993-2004 were used in
      the study. The vaccines studied included Purified Chick Embryo Cell Vaccine
      (Kaketsuken, Japan and Rabipur, India), Purified Vero cell Rabies Vaccine
      (Verorab, France), Human Diploid Cell Vaccine (MIRV, France and Rabivax, Adsorbed
      and Lyophilized, India) and Rhesus Diploid Rabies Vaccine (adsorbed, USA).
      Interestingly, it was revealed that an higher antigenecity of rabies vaccines
      viz. potency of > or = 5 IU per single intramuscular dose did not result in
      significantly higher immunogenecity, as measured by rabies virus neutralizing
      antibody (RVNA) titers in the vaccinees, both on day 14 (t = 0.42, p > 0.66, GMR
      = 1.06, 95% CI of GMR = 0.82, 1.37) and day 90 (t = 0.80, p > 0.43, GMR = 1.15,
      95% CI of GMR = 0.74, 1.14). However, as there are no reports of meta-analysis of
      cell culture human rabies vaccine trials, to confirm this observation the authors
      recommend further studies in this regard.

PMID- 17033271
TI  - Validation and clinical utility of a simple in-home testing tool for sleep
      disordered breathing and arrhythmias in heart failure: results of the Sleep
      Events, Arrhythmias, and Respiratory Analysis in Congestive Heart Failure
      (SEARCH) study.
AB  - Fifty patients with New York Heart Association class III systolic heart failure
      were enrolled in this prospective multicenter study that compared the diagnostic
      accuracy of a home-based cardiorespiratory testing system with standard attended
      polysomnography. Patients underwent at least 2 nights of evaluation and were
      scored by blinded observers. At diagnostic cutoff points of > or =5, > or =10,
      and > or =15 events per hour for respiratory disturbance severity,
      polysomnography demonstrated a sleep-disordered breathing prevalence of 69%, 59%,
      and 49%, respectively. Compared with polysomnography, the cardiorespiratory
      testing system demonstrated predictive accuracies of 73%, 73%, and 75%, which
      improved to 87%, 87%, and 83%, respectively, when analysis of covariance
      suggested reanalysis omitting one site's data. The system accurately identified
      both suspected and unsuspected arrhythmias. The device was judged by 80% of
      patients to be easy or very easy to use, and 74% of patients expressed a
      preference for the in-home system. Therefore, this system represents a reasonable
      home testing device in these patients.

PMID- 17033272
TI  - Brain natriuretic peptide levels and response to cardiac resynchronization
      therapy in heart failure patients.
AB  - The authors used brain natriuretic peptide (BNP) as a reliable marker to identify
      nonresponders to cardiac resynchronization therapy (CRT) in patients with
      advanced heart failure. The study included 70 patients with left ventricular
      dysfunction (mean ejection fraction, 21+/-4%) and left bundle branch block (QRS
      duration, 164+/-25 milliseconds) treated with CRT. The authors reviewed data on
      New York Heart Association functional class, baseline ejection fraction, sodium,
      creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy.
      The authors compared results of 42 patients who survived (973+/-192 days) after
      CRT implantation (responders) to those of 28 patients (nonresponders) who either
      expired (n=21) or underwent heart transplantation (n=5) or left ventricular
      assist device implantation (n=2) after an average of 371+/-220 days. Mean BNP
      levels after 3 months of CRT decreased in responders from 758+/-611 pg/mL to
      479+/-451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels
      from 1191+/-466 pg/mL to 1611+/-1583; P=.046. A rise in BNP levels was associated
      with poor response (death or need for transplantation or left ventricular assist
      device and impaired long-term outcome), which makes it a good predictor to
      identify such patients.

PMID- 17033273
TI  - Randomized, double-blind comparison of acute beta1-blockade with 50 mg metoprolol
      tartrate vs 25 mg carvedilol in normal subjects.
AB  - Differential efficacy of immediate-release metoprolol tartrate and carvedilol in
      the treatment of congestive heart failure remains a subject of ongoing debate.
      The degree of beta1-blockade can be assessed by percentage reduction of exercise
      heart rate. Twelve healthy subjects underwent symptom-limited cardiopulmonary
      exercise testing repeated weekly and 2 hours after randomized, double-blind
      administration of 50 mg metoprolol tartrate vs 25 mg carvedilol. Baseline heart
      rate, heart rate at 40% and 70% peak O2 consumption, and maximal exercise were
      significantly blunted more by metoprolol tartrate than by carvedilol (P<.05 for
      all). Peak O2 consumption was significantly reduced by metoprolol tartrate
      (P<.03) but not by carvedilol (P=.054). The change in O2 consumption was
      significantly correlated with the degree of beta1-blockade (r =0.45; P<.05). In
      healthy subjects, a higher degree of beta1-blockade is achieved with 50 mg
      metoprolol tartrate compared with 25 mg carvedilol.

PMID- 17033274
TI  - Prevalence and clinical implications of anemia in congestive heart failure
      patients followed at a specialized heart function clinic.
AB  - The objective of this study was to assess the prevalence of anemia and to
      investigate its association with comorbidities and its impact on clinical
      outcomes in patients with heart failure. The association of predefined anemia, as
      well as the correlation of serum hemoglobin level as a continuous variable, with
      outcomes of emergency department visits, hospitalization, and mortality was
      investigated. There were fewer anemic patients in New York Heart Association
      classes I and II than in classes III and IV. Anemia was associated with higher
      rates of emergency department visits, hospital admissions, and all-cause
      mortality. Multivariable analysis showed that anemia is independently associated
      with mortality. When hemoglobin level was considered as a continuous variable,
      the authors noted that the mortality risk correlated with hemoglobin level
      disappears when hemoglobin level exceeds 140 g/L. The authors conclude that
      anemia has strong impacts on functional class and other clinical outcomes in
      patients with heart failure.

PMID- 17033275
TI  - Increase in the QRS duration after amelioration of peripheral edema and after
      hemodialysis.
AB  - Association among weights, amplitude of QRS complexes, and QRS duration in
      patients with peripheral edema has been described. This study explored whether
      increase in QRS duration occurs with amelioration of peripheral edema or after
      hemodialysis. Sums of the amplitudes of the 12 electrocardiographic leads and
      corresponding QRS duration were measured in 12 patients with peripheral edema
      before and after loss of weight, in 28 patients with a critical illness but
      without change in their weight ("controls"), and in 1 patient before and after
      hemodialysis. QRS duration increased from 90.1+/-25.0 milliseconds to 101.7+/
      25.8 milliseconds (P=.001) in patients with peripheral edema, was unchanged in
      the controls, and increased from 87.8+/-5.9 milliseconds before to 92.7+/-6.7
      milliseconds after hemodialysis (P=.007). It is proposed that these increases in
      QRS duration are only apparent (not electrophysiologically real), representing an
      extracardiac phenomenon mediated by alterations in the composite impedance of the
      passive body volume conductor, resulting in measurement of augmented QRS
      complexes after fluid removal. The clinical implications for patients with
      congestive heart failure are discussed.

PMID- 17033276
TI  - Improving the accuracy of impedance cardiac output in the intensive care unit:
      comparison with thermodilution cardiac output.
AB  - This study examined the effect of impedance algorithm adjustment to reflect
      abnormalities found in cardiac output estimation in the intensive care unit.
      Impedance (Kubicek and Sramek equations) and thermodilution were measured
      concurrently in 61 patients. The mean difference between Kubicek and
      thermodilution (n=40) was 1.47 L/min (95% confidence interval [CI], 0.47-2.47)
      and between Sramek and thermodilution (n=54) was 2.68 L/min (95% CI, 1.93-3.44).
      Exclusion of patients with valve regurgitation improved agreement between Kubicek
      and thermodilution (n=32), with a mean difference of 2.02 L/min (95% CI, 1.10
      2.94). Multiple regression determined the role of skinfold thickness, pH,
      hematocrit, sodium, chloride, albumin, protein, and urea within impedance.
      Kubicek was recalculated using the new algorithm and recompared with
      thermodilution. The mean difference was -0.38 L/min (95% CI, -1.92 to 1.16). This
      study found poor agreement between impedance and thermodilution in critically ill
      patients, but exclusion of those with valve regurgitation and adjustment for
      hematocrit and skinfold thickness improved agreement.

PMID- 17033277
TI  - ECG changes in response to diuresis in an ambulatory patient with congestive
      heart failure.
AB  - This case report describes an ambulatory patient with congestive heart failure
      and peripheral edema who lost 18 lb in response to enhanced diuresis over the
      course of 1 week. The ECG showed increases in the amplitude of P waves, QRS
      complexes, and T waves; the duration of P waves, QRS complexes, and QT intervals;
      and the dispersion of P and QT. The clinical implications of these ECG changes
      are discussed.

PMID- 17033278
TI  - History of heart failure.

PMID- 17033281
TI  - New advances in the molecular and cellular biology of the small intestine.
AB  - Research into the structure and function of the small intestinal mucosa is
      becoming increasingly focused on the molecular and cellular biology of this
      fascinating tissue. There is a growing understanding of the factors determining
      the expression of specific genes at different stages of development and
      differentiation in the multiple cell types, and several important transcription
      factors have emerged. Recent publications have included studies of the effects of
      commensal bacteria on gene expression and the molecules producing apoptosis.
      Mechanisms of the intestinal adaptation to injury or surgery involve a number of
      hormones; current research has shown a major role for glucagon-like peptide 2.

PMID- 17033282
TI  - Nutrient absorption.
AB  - Many advances in the study of nutrient absorption have been made with the use of
      molecular and genetic techniques; however, standard in vivo studies have provided
      interesting and important new information. Omega-3 long-chain fatty acids have
      unexpected effects on lipoprotein formation and secretion in neonatal intestinal
      cells; this needs to be considered in the modification of infant formulas.
      Rexinoids affect intestinal cholesterol homeostasis via two receptors: retinoic
      acid receptor/liver X receptor (cholesterol efflux to lumen) and retinoic acid
      receptor/farnesoid X receptor (cholesterol catabolism). Absorption of the
      antioxidant plant polyphenol quercetin involves interaction with the glucose
      transporter and deglycolsylation and conjugation reactions. Cells of the
      polarized human colon cancer cell line, CaCo-2, take up phenylalanine by two
      mechanisms: passive uptake across the basolateral membrane, and temperature
      dependent transcellular movement from apical to basolateral media. Absorption of
      vitamins A and E is markedly enhanced in normal and damaged intestine by the
      administration of restructured triacylglycerols derived from fish oil and medium
      chain fatty acids. Surprisingly, dietary protein and phosphorus apparently have
      no significant effect on the efficiency of calcium absorption in adult women.
      Finally, many studies examined a variety of genes that regulate iron absorption
      and homeostasis.

PMID- 17033283
TI  - Fluid and electrolyte transport in the small intestine.
AB  - The small intestine is in a dynamic state of secretion and absorption, the sum of
      which results in net absorption. Secretion is principally the result of chloride
      and bicarbonate extrusion through apical chloride channels after the activation
      of the second messengers cAMP, cGMP, and calcium. In addition to the cystic
      fibrosis transmembrane conductance regulator, several other candidate chloride
      channels have been identified and proposed to play a role in intestinal
      secretion, including the calcium-dependent chloride channel hCLCA1. Pathways
      leading to the negative control of secretion have been described that use
      cellular messengers, including inositol (3,4,5,6) tetrakisphosphate and
      phosphatidylinositol 3-kinase, which may act via basolateral potassium channels.
      The control of ion transport can also be viewed in terms of the enteric nervous
      system. The reflex neural pathways involved in enterotoxin-induced secretion have
      been substantiated and shown to involve 5-hydroxytryptamine, substance P, and the
      neurokinin 1 and 2 receptors in the sensory arm, and vasoactive intestinal
      peptide in the secretomotor efferents. Absorption of glucose in addition to
      active cotransport with sodium via the Na/glucose cotransporter protein has also
      been shown to occur passively through a carrier-mediated mechanism, using the
      membrane protein glucose transporter protein 2.

PMID- 17033284
TI  - Recent developments in celiac disease.
AB  - Celiac disease is a common disorder associated with a substantially increased
      standardized mortality ratio if it is left untreated or if the diagnosis is
      delayed. Diagnostic sensitivity of serologic testing is improved by the addition
      of IgG-based testing to standard IgA-based serologic testing for endomysial or
      transglutaminase autoantibodies. The role of intestinal permeability testing as
      an additional tool for screening and for monitoring the response to a gluten-free
      diet is discussed. The importance of diagnosing celiac disease in two clinical
      situations is considered: first, before immune-stimulating therapy with
      interferon for viral hepatitis is begun and second, in pregnancy when not only
      maternal but also paternal celiac disease may affect fetal outcome. The strong
      genetic component of the etiology of celiac disease is illustrated by a
      monozygotic twin concordance of nearly 90%, with susceptibility conveyed by human
      leukocyte antigen (HLA) genotypes DQ2 or DQ8 and one or more non-HLA genes.
      Progress toward identifying these genes from large linkage and association
      studies is reviewed.

PMID- 17033285
TI  - Small bowel motility.
AB  - The publications relevant to small bowel motility have been concentrated during
      the past year in several main areas: further characterization of normal patterns
      of small bowel motor activity and transit, physiologic control mechanisms,
      visceral hypersensitivity, inflammation and motility, disease processes and
      dysmotility, and novel pharmacologic approaches to altered sensorimotor activity.

PMID- 17033286
TI  - Surgery of the small intestine.
AB  - The small intestine is the portal of entry of virtually all nutrients and is also
      the site of diverse inflammatory and neoplastic diseases. This field has recently
      attracted intense excitement as a result of novel clinical and experimental
      techniques, combined modality therapies, and basic science applications. This
      review will highlight important clinical advances in surgery for Crohn disease,
      short bowel syndrome, transplantation, trauma, and polyposis. Promising
      experimental approaches, novel methods of clinical assessment, and multimodality
      treatment will also be considered.

PMID- 17033287
TI  - Small bowel infections.
AB  - Infections of the human gastrointestinal tract with enteric pathogens are among
      the leading causes of disease, suffering, and death worldwide. Enteric pathogens
      are ingested from contaminated food and water and pass through the entire
      gastrointestinal tract during establishment in the host and subsequent shedding
      and spread to new hosts. Nonetheless, each pathogen exploits a unique niche
      within the intestinal tract and has developed unique strategies to interact with
      different host cells and functions. The most important and prevalent infections
      of the small intestine are caused by diarrheagenic Escherichia coli, particularly
      enterotoxigenic and enteropathogenic E. coli, rotavirus, Giardia lamblia, and
      Cryptosporidium parvum. This review focuses on recent insights into the
      pathogenesis of infections with these pathogens and host defenses against them.

PMID- 17033288
TI  - The role of nutritional deficiency in the osteopenia and osteoporosis of
      gastrointestinal diseases.

PMID- 17033289
TI  - Enteral feeding.
AB  - In this review, topics with scientific strength, topical interest, and
      controversy were selected. Over the past 50 years, malnutrition has become
      increasingly recognized as a cause of increased morbidity and mortality in
      hospital patients. From 1970 to 1980, parenteral nutrition was advocated as the
      most appropriate form of nutritional therapy for hospital patients. Since then,
      parenteral nutrition has been replaced by enteral nutrition as the best way of
      delivering nutrients to hospital patients. The timing of enteral nutrition has
      been debated. Should it be instituted early, within the first 24 hours? In
      addition, enteral nutrition containing immune-enhancing nutrients such as
      arginine, omega-3 fatty acids, glutamine, and nucleotides has been advocated for
      critically ill patients. The relative merits of enteral versus total parenteral
      nutrition continue to be debated. Questions about possible complications related
      to enteral nutrition have been raised. Patients are at risk of nosocomial
      pneumonia from aspiration and at risk of bowel ischemia because enteral nutrition
      increases intestinal oxygen consumption. Steroids are often used to treat Crohn
      disease, but because of undesirable side effects, various techniques have been
      used to reduce steroid dependency. Enteral nutrition has been advocated as a way
      of reducing steroid dependency. Finally, enteral nutrition is routinely used to
      feed demented patients and those in a vegetative state. It is not clear whether
      this practice alters outcome or quality of life.

PMID- 17033290
TI  - Obesity pharmacology: past, present, and future.
AB  - Over the past several years, the pharmacologic treatment of obesity has undergone
      changes in safety, efficacy, and therapeutic targeting. The prevalence of cardiac
      valvulopathy associated with treatment with phentermine, fenfluramine, and
      dexfenfluramine is now becoming clarified with the publication of longer-term
      studies. Phenylpropanolamine, a well-known over-the-counter appetite suppressant,
      was recently removed from the market in the United States because of an increased
      risk of hemorrhagic stroke in women. In contrast, two currently approved
      medications, sibutramine and orlistat, have been shown to be safe and moderately
      effective for weight loss with documented beneficial effects on cardiovascular
      risk factors. Three other drugs, bupropion, topiramate, and ciliary neurotrophic
      factor, are undergoing clinical trials for obesity based on empirical
      observations. Most promising are the advances in genetics and molecular biology
      that are beginning to elucidate new targets for controlling appetite and energy
      utilization. These therapeutic agents will likely herald a second generation of
      anti-obesity medications over the next decade.

PMID- 17033291
TI  - Malnutrition and gastrointestinal disease.
AB  - The recognition of several disease processes that cause or are associated with
      gastrointestinal malabsorption has led to extensive investigation into their
      pathogenesis, diagnosis, and treatment. This review of selected articles covers a
      range of subjects related to some of the more common malabsorptive disease.
      Selected topics including celiac disease, disaccharidase deficiencies, short
      bowel syndrome, and Crohn disease are discussed.

PMID- 17033292
TI  - Diet, folate, and colon cancer.
AB  - Evidence emerging from many different types of experimental designs continues to
      support the concept that dietary habits and nutritional status play important
      roles in determining the risk of colorectal cancer. This field of investigation
      is nevertheless very confusing, particularly because longstanding hypotheses,
      such as the presumed protective effects of fruits, vegetables, and fiber, have
      recently been challenged by well-designed prospective trials. The search for
      individual components in the diet that convey protection continues: calcium,
      folate, selenium, and omega-3 fatty acids are the leading candidates in this
      regard. There is also growing interest in other plant-based compounds, so-called
      phytochemicals, although our understanding of their effects is quite rudimentary
      at present. Although the inconsistencies in this field make it tempting to
      minimize its import, there is little question that diet has a major impact on
      colorectal cancer risk; diligent attention to the rigorous conduct of studies and
      their interpretation will likely clarify these relationships over the next
      decade, much to the benefit of public health.

PMID- 17033293
TI  - Probiotics in gastroenterology.
AB  - Recent evidence has suggested the potential therapeutic role for probiotics in
      the prevention or treatment of gastrointestinal diseases. Several studies have
      shown that probiotics are of benefit in gastrointestinal infections, including
      viral diarrhea, Clostridium difficile-associated diarrhea, traveler's diarrhea,
      and antibiotic-associated diarrhea. Recent data support the potential beneficial
      therapeutic effect in inflammatory bowel disease as well. Other possible
      indications for probiotic treatment include Helicobacter pylori infection,
      irritable bowel syndrome, and radiotherapy-associated diarrhea. It is important
      to select well-characterized preparations; in fact, the viability and survival of
      many available preparations are unproven. More precise information on the
      mechanisms by which probiotic strains exert their beneficial effects in vivo is
      needed. This may provide the scientific rationale for the selection of the best
      probiotic strains to use in the performance of large, double-blind, controlled
      clinical trials.

PMID- 17033294
TI  - Nutrition in the elderly.
AB  - It is now well accepted that older persons experience a physiologic anorexia, the
      anorexia of aging, which is caused by alterations in hedonic qualities of food,
      fundal compliance, and increased leptin levels. Depression is the most common
      pathologic cause of weight loss in older persons. Older persons fail to recognize
      thirst and as such have an increased risk of dehydration. Alterations in brain
      membrane fatty acids can lead to cognitive impairment in older persons.

PMID- 17033295
TI  - Current nutrition in liver disease.
AB  - Malnutrition is common in severe liver disease. Assessment of malnutrition
      usually requires a subjective global assessment of the patient with a few
      additional tests that often include handgrip strength and arm-muscle
      circumference. The severity of liver disease correlates well with the severity of
      malnutrition, which has prognostic value. Malnutrition is multifactorial, is
      difficult to correct, and occurs in liver disease independently of the etiology
      of hepatic injury. Patients who have severe protein-calorie malnutrition require
      diets with high calorie and protein intake, even in the presence of hepatic
      encephalopathy. Some forms of complementary and alternative medicine are
      frequently used in patients with advanced liver disease, but supporting
      scientific data is needed. Obesity is detrimental to patients with advanced liver
      disease and is of greater concern in liver transplant candidates because it
      increases transplant-related morbidity. Data detailing the effects of aggressive
      nutritional support before transplantation are scarce, and more studies are
      needed.

PMID- 17033297
TI  - Bibliography current world literature.

PMID- 17033296
TI  - Cholesterol absorption.
AB  - Cholesterol absorption is a key regulatory point in human lipid metabolism
      because it determines the amount of endogenous biliary as well as dietary
      cholesterol that is retained, thereby influencing whole body cholesterol balance.
      Plant sterols (phytosterols) and the drug ezetimibe reduce cholesterol absorption
      and low-density lipoprotein cholesterol in clinical trials, complementing the
      statin drugs, which inhibit cholesterol biosynthesis. The mechanism of
      cholesterol absorption is not completely known but involves the genes ABC1,
      ABCG5, and ABCG8, which are members of the ATP-binding cassette protein family
      and appear to remove unwanted cholesterol and phytosterols from the enterocyte.
      ABC1 is upregulated by the liver X (LXR) and retinoid X (RXR) nuclear receptors.
      Acylcholesterol acytransferase-2 is an intestinal enzyme that esterifies absorbed
      cholesterol and increases cholesterol absorption when dietary intake is high. New
      clinical treatments based on better understanding of absorption physiology are
      likely to substantially improve clinical cholesterol management in the future.

PMID- 17033299
TI  - Hepatobiliary pathology.
AB  - Technologic advances using cDNA microarray hybridization, liver diseases
      characterized by mitochondrial DNA depletion, and new work characterizing bile
      salt transport problems in familial intrahepatic cholestasis syndromes were some
      of the major highlights of this past year. Analysis of normal livers by cDNA
      microarrays disclosed 2418 unique gene transcripts encoding a host of cellular
      structural and functional proteins. This technique was also applied to
      hepatocellular carcinoma, where enhanced expression of a number of genes involved
      in antiapoptosis and cell transformation may shed additional light on the process
      of hepatocarcinogenesis. Mitochondrial DNA depletion seen in Navajo
      neurohepatopathy and in respiratory chain disorders of infancy was associated
      with cholestasis and cirrhosis in the former and microvesicular steatosis and
      oncocytic transformation (mitochondrial hyperplasia) in the latter. Pathologists
      who routinely examine liver biopsies after liver or bone marrow transplantation
      should be aware of unusual biopsy features that mimic other diseases, such as the
      autoimmune hepatitis-like syndrome that may follow liver transplantation and
      chronic graft-versus-host disease that clinically and pathologically resembles
      acute hepatitis.

PMID- 17033300
TI  - Inherited metabolic disease.
AB  - The elucidation of metabolic pathways and the genetic basis for diseases of the
      liver continues to increase our understanding of disease pathogenesis and advance
      treatment options. This selective review covers a wide range of subjects, from
      the identification of novel proteins and the importance of specific transport
      pathways to phenotypic expression of disease and management of acute liver
      failure. Three selected disorders--Wilson disease, genetic hemochromatosis and
      other hereditary iron overload disorders, and alpha(1)-antitrypsin disease--are
      the focus of this review.

PMID- 17033301
TI  - Drug-induced liver disease.
AB  - Although the year 2001 did not see any prescription drugs withdrawn because of
      drug-induced liver disease, the US Food and Drug Administration requested that
      dietary supplements containing comfrey be taken off the market because of the
      danger of hepatic injury. The Food and Drug Administration remains very involved
      in the process by which drug-induced liver disease can be detected early in drug
      development and in the determination of how best to prevent hepatotoxicity after
      drug approval. A workshop on drug-induced liver disease cosponsored by the Food
      and Drug Administration, the Pharmaceutical Research and Manufacturers
      Association, and the American Association for the Study of Liver Diseases was
      held in Washington, DC, in February 2001, and the resulting white paper outlined
      several areas for research. A number of agents were newly described as causing
      various forms of liver injury, and several others had drug-induced liver disease
      confirmed by additional reports. Several investigators dealt with the
      difficulties inherent in establishing causality of drug-induced liver disease and
      the potential negative consequences of wrongly attributing hepatotoxicity to a
      particular agent. In one recent series, more than half the instances of alleged
      drug-induced liver disease were found to have other causes, often leading to a
      delay in the actual diagnosis and appropriate management. Case reports in
      particular were often misleading. Although several drug assessment scales have
      been developed, none appears to be foolproof.

PMID- 17033302
TI  - Cholestatic syndromes.
AB  - Further insights into the molecular regulation of bile acid transport and
      metabolism have provided the basis for a better understanding of the pathogenesis
      of cholestatic liver diseases. Novel insights into the mechanisms of action of
      ursodeoxycholic acid should advance our understanding of the treatment of
      cholestatic liver diseases. Mutations of transporter genes can cause hereditary
      cholestatic syndromes in both infants and adults as well as cholesterol gallstone
      disease. Important studies have been published on the pathogenesis, clinical
      features, and treatment of primary biliary cirrhosis, drug-induced cholestasis,
      and cholestasis of pregnancy.

PMID- 17033303
TI  - Viral hepatitis.
AB  - Viral hepatitis affects millions of people worldwide, making it one of the most
      important diseases in the field of hepatology. The response to the hepatitis A
      vaccine is optimal when targeted to patients with chronic hepatitis before
      development of hepatic decompensation. A new triple antigen vaccine for hepatitis
      B virus produces a greater degree of protection. Lamivudine can achieve a 3-to 4
      log reduction in serum viral levels in patients with chronic hepatitis B
      infection. Lamivudine-resistant mutants appear in more than 50% of patients after
      prolonged treatment. Entecavir can be given safely for a short time and causes a
      pronounced reduction in hepatitis B viral DNA levels with slower rebound after
      stopping therapy than has been reported with lamivudine. Pegylated interferon has
      sustained absorption, a slower rate of clearance and a longer half-life than
      unmodified interferon alfa. Pegylated interferon alfa-2a administered once weekly
      is more effective than standard interferon alfa-2a administered three times
      weekly. In patients with chronic hepatitis C infection, the most effective
      therapy is the combination of pegylated interferon plus ribavirin. Other major
      advances in the field of viral hepatitis during the past year are highlighted.

PMID- 17033304
TI  - Autoimmune liver disease.
AB  - Autoimmune hepatitis is as virulent in the elderly as in the young, and initial
      treatment should be similar. Antiphospholipid antibodies should be sought in all
      patients with a history of fetal loss or arterial or venous thrombosis. The C282Y
      mutation in the HFE hemochromatosis gene occurs more commonly in autoimmune
      hepatitis than in normal subjects, but it is not associated with distinctive
      features. Children with autoimmune hepatitis may have abnormal cholangiogram
      results, but the syndrome of autoimmune sclerosing cholangitis does not affect
      immediate prognosis. Bile duct changes, including destructive cholangitis, can be
      incidental findings that have no clinical expression or therapeutic consequence.
      In South America, DRB1*1301 is associated with protracted hepatitis A virus
      infection which may enhance exposure to hepatic self-antigens in children.
      Interferon gamma-inducible protein 10 may be an important chemokine that promotes
      liver damage by attracting activated T cells. Transcripts of Fas ligand are
      abnormally increased in autoimmune hepatitis, and apoptotic dysfunction may
      contribute to disease progression. Pregnancy is not contraindicated in autoimmune
      hepatitis, and cyclosporine may be effective as first-line therapy.

PMID- 17033305
TI  - Hepatocellular carcinoma.
AB  - The number of papers published regarding hepatocellular carcinoma increased
      remarkably over the previous year. The 1-year survival for hepatocellular
      carcinoma has only improved slightly over the past 20 years, while the overall
      survival has remained unchanged. Hepatitis B genotypes, specifically genotype B,
      correlate with better response and survival in patients with hepatocellular
      carcinoma caused by this chronic infection. A consensus conference recommended
      that patients with Child-Turcotte-Pugh class A or B cirrhosis should be screened
      with ultrasound and alpha-fetoprotein measurement every 6 months. Using
      microarray technology, several groups established the gene expression for human
      hepatocellular carcinoma including the identification of potential genes involved
      in hepatic carcinogenesis. Dynamic gadolinium MRI is the preferred imaging of
      choice for the evaluation of hepatocellular carcinoma, but contrast-enhanced
      power Doppler ultrasound is a new imaging technique able to differentiate
      neoplastic from nonneoplastic liver lesions. Overall, transplantation is the best
      long-term therapeutic option, but in patients without portal hypertension and
      well-preserved liver function, resection may be preferable.

PMID- 17033306
TI  - Portal hypertension.
AB  - Portal hypertension is the main complication of cirrhosis and is responsible for
      its most common complications: variceal hemorrhage, ascites, and portosystemic
      encephalopathy. Portal hypertension is the result of increased intrahepatic
      resistance and increased portal venous inflow. Vasodilatation (splanchnic and
      systemic) and the hyperdynamic circulation are hemodynamic abnormalities typical
      of cirrhosis and portal hypertension. Gastroesophageal varices result almost
      solely from portal hypertension, although the hyperdynamic circulation
      contributes to variceal growth and hemorrhage. Ascites results from sinusoidal
      hypertension and sodium retention, which is in turn secondary to vasodilatation
      and activation of neurohumoral systems. Hepatic hydrothorax results from the
      passage of ascites across the diaphragm and into the pleural space. The
      hepatorenal syndrome represents the result of extreme vasodilatation with an
      extreme decrease in effective blood volume that leads to maximal activation of
      vasoconstrictive systems, renal vasoconstriction, and renal failure. Spontaneous
      bacterial peritonitis is a potentially lethal infection of ascites that occurs in
      the absence of a local source of infection. Portosystemic encephalopathy is a
      consequence of both portal hypertension (shunting of blood through portosystemic
      collaterals) and hepatic insufficiency resulting in the accumulation of
      neurotoxins in the brain.

PMID- 17033307
TI  - Cholangiocyte biology.
AB  - Due in part to the recent development of new experimental models, cholangiocytes-
      the epithelial cells that line the bile ducts--are increasingly recognized as
      important transporting epithelia actively involved in the absorption and
      secretion of water, ions, and solutes. New biologic concepts have emerged
      including the identification and topography of receptors and flux proteins
      involved in the molecular mechanisms of ductal bile secretion. Individually
      isolated or perfused bile duct units from livers of rats and mice serve as new,
      physiologically relevant in vitro models to study cholangiocyte transport.
      Biliary tree dimensions and novel insights into anatomic remodeling of
      proliferating bile ducts have emerged from three-dimensional reconstruction using
      computed tomographic scanning and sophisticated software. Moreover, new
      pathologic concepts have arisen regarding the interaction of cholangiocytes with
      pathogens. These concepts may provide the framework for new therapies for the
      cholangiopathies, a group of important hepatobiliary diseases in which
      cholangiocytes are the target cell.

PMID- 17033308
TI  - Cholesterol gallstones.
AB  - Cholesterol cholelithiasis is common in Western populations and represents a
      consequence of altered cholesterol homeostasis. Gallstones form because of a
      complex and incompletely understood series of metabolic and physicochemical
      events that promote cholesterol crystallization in bile. In the context of
      current paradigms, this article reviews recent progress in research on biliary
      lipid metabolism and the pathogenesis of cholesterol gallstones.

PMID- 17033309
TI  - Sclerosing cholangitis.
AB  - Primary sclerosing cholangitis in children can mimic autoimmune hepatitis in the
      absence of inflammatory bowel disease. Most adult patients have been identified
      with human leukocyte antigens that either predispose or protect against disease.
      Novel class I alleles and cytokine polymorphisms may also contribute to disease
      susceptibility. Primary alpha-hemolytic streptococci infection does not appear to
      directly cause primary sclerosing cholangitis. Promising diagnostic modalities
      such as single photon emission tomography require further study in comparison
      with cholangiographic techniques. Positron-emission tomography and DNA cytometry
      appear promising for confirming occult cholangiocarcinoma when present. The
      chemoprevention effects of ursodeoxycholic acid on colorectal dysplasia await
      further investigation. Initial results from high-dose ursodeoxycholic acid in
      halting disease progression, however, suggest a beneficial effect. In contrast,
      the impact of endoscopic therapy on natural history remains unresolved. Although
      liver transplantation continues to be effective for end-stage liver disease,
      disease recurrence in the allograft is a controversial topic.

PMID- 17033310
TI  - Endoscopic management of biliary disease.
AB  - Therapeutic biliary endoscopy continues to evolve. Key articles this year
      primarily involve biliary stenting and biliary stone removal, the two important
      maneuvers available to the biliary endoscopist. The issues addressed in this
      review include follow-up after the use of multiple stents for benign strictures,
      unilateral versus bilateral stenting for Klatskin tumors, stent types and
      placement positions, the timing and approach to choledocholithiasis in the
      context of anticipated cholecystectomy, and resistant biliary duct stones.

PMID- 17033311
TI  - Bibliography current world literature.

PMID- 17033312
TI  - Professor Dame Sheila Sherlock (1918-2001).

PMID- 17033313
TI  - Inflammatory bowel disease: genetics and much more.

PMID- 17033314
TI  - Update on genetics of inflammatory bowel disease.
AB  - Complex genetic disorders such as inflammatory bowel disease (IBD) result from
      the interplay between multiple genetic and environmental risk factors. The recent
      identification of variants of the CARD15/NOD2 protein as contributing to Crohn
      disease represents a major advance in defining disease pathogenesis. CARD15/NOD2
      is expressed in monocytes and is capable of activating nuclear factor kappa B (NF
      kappaB). Crohn disease-associated mutations in CARD15/NOD2 predominate in its C
      terminus leucine-rich repeat domain, which is required for bacterial
      lipopolysaccharide-dependent induction of NF-kappaB activity. The relative risk
      of developing Crohn disease is estimated to be in the range of 2 to 3 in people
      carrying one mutation and 20 to 40 in people carrying two mutations in
      CARD15/NOD2. Homozygote and compound heterozygote carriers of CARD15/NOD2
      mutations are characterized by an earlier age of onset, less involvement of the
      left colon, and positive association with stricturing disease. However, even
      carriers of two CARD15/NOD2 mutations have limited disease penetrance (ie, only a
      minority will develop the disease), suggesting that additional interacting genes
      and environmental triggers are required for disease expression. Several
      additional genetic regions have been implicated through genetic linkage and
      association studies.

PMID- 17033315
TI  - Epidemiology of inflammatory bowel disease.
AB  - Despite the apparent continuous increase of the incidence of inflammatory bowel
      disease (IBD) in some populations, or some sections of populations such as
      British children, the origin of these conditions remains obscure. Epidemiological
      studies of specific risk factors continue to yield contradictory and inconclusive
      results. However, studies of exposure and comorbidity, coupled with genetic and
      molecular studies, expand our knowledge and will facilitate more sophisticated
      research in the near future. Our understanding of the genetic basis of IBD is
      improving, but genetic anticipation as an explanation for increasing incidence
      rates appears less probable. The benefit of giving up smoking has been
      demonstrated in Crohn's disease patients, because smoking influences disease
      activity. The increased cancer risk in IBD is a concern, but despite this, the
      overall mortality in IBD is no higher than that of the general population.

PMID- 17033316
TI  - Immunopathogenesis of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is characterized by inflammation that results
      from the interaction between the various components of the mucosal immune system
      and the microenvironment. These components-lu}inal antigens, intestinal
      epithelial cells (IEC), lymphocytes, and cells of the innate and adaptive immune
      system and their secreted mediators (cytokines and chemokines)-contribute to the
      cascade of events that ends in intestinal and systemic damage in a genetically
      predisposed host. The origin of IBD is as yet unknown, but the beginning of the
      third millennium has brought several new insights into the immune aberrations in
      IBD. The progress achieved last year in each component of IBD pathogenesis will
      be reviewed. In each section, an attempt to develop correlations between
      experimental findings and human disease is made.

PMID- 17033317
TI  - Osteoporosis and other complications of inflammatory bowel disease.
AB  - Osteoporosis has received increasing attention as a potential complication of
      inflammatory bowel disease (IBD). The first population-based data on incidence of
      fractures in an IBD population were published this past year. The incidence of
      fractures was one per 100 patient years. Compared with the general population,
      the fracture rate was increased; however, the relative risk was 1.4 and,
      therefore, not as high as might be expected from the myriad of studies reporting
      high rates of osteopenia measured by dual energy x-ray absorptiometry (DXA).
      Another area receiving increasing attention is that of the enhanced risk of
      venous thrombosis in patients with IBD. The first population-based incidence
      rates of venous thrombosis in IBD were also published this past year and showed
      that IBD patients are affected by venous thrombosis at a rate of approximately
      one per 200 patient years. The relative risk for venous thrombosis compared with
      the general population was 3.5. Several studies have reported on associated risk
      markers or genetic clotting abnormalities, but no clear paradigm has emerged to
      account for those patients who will suffer a clot. Finally, the first North
      American population-based study was published, quantifying the prevalence rates
      of extraintestinal manifestations in patients with IBD for at least 10 years.
      Some gender- and disease-specific findings emerged. This study found that iritis
      and uveitis were more common in female patients with ulcerative colitis (3.2%),
      primary sclerosing cholangitis (PSC) was most common in male patients with
      ulcerative colitis (3%), ankylosing spondylitis was most common in male patients
      with Crohn disease (2.7%), and erythema nodosum was most likely to occur in
      female patients with Crohn disease (1.9%).

PMID- 17033318
TI  - Advances in the medical therapy of inflammatory bowel disease.
AB  - The medical therapy of inflammatory bowel disease (IBD) has advanced
      significantly over the past year. Serologic markers of IBD have been further
      investigated and better defined, showing some discriminatory power with potential
      therapeutic implications. Studies of azathioprine and 6-mercaptopurine
      metabolites will make it easier and safer to use these effective drugs. Clinical
      data using other immunomodulators, including 6-thioguanine, mycophenolate
      mofetil, cyclosporine, and tacrolimus, continue to accrue with positive results.
      Infliximab has become even more firmly established as a reliable and effective
      therapy for active and fistulizing Crohn disease and may even be helpful in some
      patients with resistant ulcerative colitis. However, the recognition of potential
      complications of infliximab therapy has increased with the accumulated clinical
      experience. Results from trials of other biologic therapies directed at tumor
      necrosis factor alpha have been disappointing so far, although preliminary
      studies with biologics directed at adhesion molecules are encouraging. Growing
      appreciation of the importance of the enteric microflora in IBD has led to a
      considerable interest in manipulating intestinal bacteria for therapeutic
      benefit, and trials of both probiotics and prebiotics show promise.

PMID- 17033319
TI  - Surgical treatment of inflammatory bowel disease.
AB  - Appropriate surgical management of Crohn disease is predicated on multiple
      variables, but stricturoplasty is generally reserved for small bowel disease,
      whereas resection is utilized in ileocolonic inflammation and favored for large
      bowel disease. Laparoscopic resection is becoming increasingly useful and
      justified for ileocolic resections, and segmental resection should be strongly
      considered for limited large bowel inflammation. Some centers are also using a
      laparoscopic approach for the surgical treatment of acute or chronic ulcerative
      colitis, although the benefits are less apparent. Proctocolectomy with ileostomy
      or ileal pouch-anal anastomosis returns the patient's quality of life to a level
      comparable to that enjoyed by the general population. Creation of a pouch is
      performed in most instances, but early complications may warrant pouch revision
      and later complications, such as pouchitis, can mandate pouch excision.

PMID- 17033320
TI  - Gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) affects many patients and has a negative
      effect on quality of life. Along with the increasing prevalence of GERD is an
      increase in GERD-related complications, including Barrett esophagus and
      esophageal adenocarcinoma. The past year has yielded new insights into the
      pathophysiology of GERD that can help us to better understand the relationship
      between reflux episodes and symptoms of mucosal damage and to provide a tailored
      treatment targeting individual pathophysiologic defects. The issues addressed in
      this report include gastric secretory and motor dysfunction; failure of the
      antireflux barrier caused by hiatal hernia and transient lower esophageal
      sphincter relaxations; characterization of the refluxate, particularly of nonacid
      reflux; prevalence and prognostic value of esophageal dysmotility in GERD;
      presence and eradication of Helicobacter pylori; Barrett esophagus and
      extraesophageal manifestations of GERD; and, finally, advances in medical,
      endoscopic, and surgical treatments of GERD.

PMID- 17033321
TI  - Esophageal motor disorders.
AB  - Refinements continue in the measurement, display, and interpretation of pressure
      events that serve as signatures of esophageal motor disorders, and esophageal
      manometry retains its position as the diagnostic gold standard. The focus of
      attention remains with achalasia, not because of pathophysiologic developments or
      changing prevalence, but in response to the growing interest in minimally
      invasive surgery and its success. Some controversy remains regarding the role of
      preoperative motility assessments in patients undergoing antireflux surgery, as
      peristaltic features do not solely predict outcome. The disconnect between motor
      dysfunction and symptoms continues to promote careful consideration of sensory
      dysfunction as a component of esophageal motor disorders.

PMID- 17033322
TI  - Chest pain of esophageal origin.
AB  - Chest pain of esophageal origin is the most common atypical/extraesophageal
      manifestation of gastroesophageal reflux disease (GERD). We are increasingly
      recognizing the important role of the cardiologist in making the diagnosis.
      Studies continue to focus on the mechanisms of pain in this challenging group of
      patients. Factors that determine the development and persistence of visceral
      hypersensitivity are currently under investigation. Invasive diagnostic studies
      have been replaced by therapeutic trials or empirical therapies. Proton pump
      inhibitors have been demonstrated to be the most effective treatment for GERD
      related noncardiac chest pain (NCCP). Pain modulators remain the primary therapy
      for non-GERD-related NCCP. Sertraline is the first selective serotonin reuptake
      inhibitor to demonstrate a significant improvement in chest pain symptoms.

PMID- 17033323
TI  - Barrett esophagus.
AB  - A number of publications have provided valuable insight into and data on the
      epidemiology, pathogenesis, diagnosis, risk factor evaluation, and treatment of
      patients with Barrett esophagus. Although the incidence of esophageal
      adenocarcinoma has rapidly increased over the past two decades, it is not clear
      whether there has been a parallel increase in the frequency of Barrett esophagus.
      The issue of surveillance endoscopy in patients with Barrett esophagus remains
      controversial; prospective data are still lacking. Bile reflux plays an important
      role in the pathogenesis of Barrett esophagus; however, this usually occurs in
      the presence of acid. Newer technology and techniques, including chromoendoscopy,
      magnification endoscopy, optical coherence tomography, and spectroscopy, have
      opened the field by providing a more accurate and "nonbiopsy" diagnosis of
      intestinal metaplasia and dysplasia. The field of biomarkers remains continues to
      expand and is providing insight into risk stratification of patients with Barrett
      esophagus. The exact role of acid suppression in patients with this premalignant
      disease remains controversial, and endoscopic therapies appear promising.

PMID- 17033324
TI  - Endoscopic therapeutic esophageal interventions.
AB  - In Western countries, many esophageal diseases result from uncontrolled
      gastroesophageal reflux. Treatments for Barrett esophagus, peptic strictures, and
      esophageal adenocarcinoma still account for a large portion of the esophageal
      interventions performed by therapeutic endoscopists. In addition to continued
      refinements in the treatment of these sequelae, new endoscopic therapies have
      emerged to treat gastroesophageal reflux disease itself. This article reviews the
      available literature on new endoscopic antireflux procedures along with other
      advances that give the endoscopist unprecedented options in the treatment of
      esophageal diseases.

PMID- 17033325
TI  - Esophageal cancer.
AB  - Despite advances in our knowledge of esophageal cancer, 50% of patients present
      with incurable disease, and the overall survival after diagnosis is poor. The
      incidence of esophageal adenocarcinoma of the distal esophagus is rising at a
      rapid rate in developed countries. Recent advances in the epidemiology of
      esophageal cancer offer insights into preventive strategies in patients who are
      at risk. New developments in diagnosis may help detect the disease at an early
      stage. New diagnostic modalities permit more accurate staging procedures and
      allow appropriate selection of therapy. New studies provide more information on
      multimodality therapy for esophageal cancer, and new endoscopic techniques allow
      resection of small lesions without surgery. New stent designs provide better
      palliation by providing tumor ingrowth. These developments in the treatment of
      esophageal cancer are the focus of this review.

PMID- 17033327
TI  - Bibliography current world literature. Inflammatory bowel disease.

PMID- 17033326
TI  - Esophageal carcinoma: surgery, radiotherapy, and chemotherapy.
AB  - Several new developments in the potentially curative therapy of esophageal cancer
      have drawn attention over the past year. There is a potential benefit of
      centralization of esophagectomies in dedicated centers. Early mucosal lesions are
      increasingly treated by local ablative therapy. Tumors invading the submucosa are
      preferably treated by surgical resection. There is ongoing controversy about the
      optimal surgical approach. Positron emission tomography scanning is a promising
      tool in the preoperative work-up but needs critical evaluation. The question of
      whether chemoradiation with voice preservation (followed by salvage surgery in
      case of tumor recurrence) can replace pharyngolaryngectomy in patients with
      cervical esophageal cancer is still unanswered. A review of eight randomized
      trials demonstrated that chemoradiation as primary treatment of esophageal cancer
      provides an absolute reduction of mortality. The addition of new drugs like
      paclitaxel and irinotecan into induction regimens for the treatment of advanced
      disease results in higher response rates but also in increased toxicity.
      Preoperative radiotherapy as single modality treatment does not improve overall
      survival, whereas the benefit of preoperative chemotherapy and chemoradiation has
      not been proven unequivocally. Several retrospective studies with a small number
      of patients suggest that local response parameters like pathologic complete
      response and downstaging of regional lymph node (N) status are correlated with
      longer survival.

PMID- 17033328
TI  - Pancreas.

PMID- 17033329
TI  - Receptor biology and intracellular regulatory mechanisms in pancreatic acinar
      cells.
AB  - Continuing progress is being made in understanding the regulation of pancreatic
      acinar cell function by receptor-activated intracellular signaling mechanisms.
      Knowledge of how ligands interact at the molecular level with their receptors and
      activate heterotrimeric G proteins is increasing. In addition to inositol
      trisphosphate, intracellular messengers include cyclic ADP ribose, nicotinic acid
      adenine dinucleotide phosphate, arachidonic acid, and diacylglycerol. Ca
      signaling involves the interaction of inositol trisphosphate, cyclic ADP ribose,
      and nicotinic acid adenine dinucleotide phosphate with distinct subcellular Ca
      stores. Ca signals ultimately induce exocytosis of zymogen granules and
      identification of the proteins involved on the granule and plasma membrane, and
      understanding of their roles is continuing. Other receptor-activated signaling
      pathways primarily regulate nonsecretory events. Considerable progress has been
      made in understanding how the mammalian target of rapamycin pathway regulates
      protein synthesis through translation factors and ribosomal proteins. Other
      pathways in acinar cells include the mitogen-activated protein kinases, the
      tyrosine kinases, and the transforming growth factor-beta-Smad pathways.

PMID- 17033330
TI  - Neurohormonal control of pancreatic exocrine secretion.
AB  - The neurohormonal control of pancreatic exocrine secretion is a complex
      interaction of multiple pathways involving a large number of gut hormones,
      neurotransmitters, and neuropeptides. Recent studies have elucidated a role for
      cholecystokinin in the regulation of bicarbonate and fluid secretion from
      pancreatic duct cells and suggested that cholecystokinin stimulation of human
      pancreatic acinar cells is likely regulated by an indirect mechanism of
      stimulation of afferent neurons. Evidence supports the regulation of potassium
      channels in rat pancreatic acinar cells by the cyclic AMP-mediated agonist
      secretin. Mechanisms for the regulation of cholecystokinin and secretin release
      by releasing factors have also been elucidated. The area postrema has been
      implicated in the mediation of inhibition of pancreatic secretion by the gut
      hormones peptide YY and pancreatic polypeptide. The neurotransmitter serotonin
      has been demonstrated to play a role in acid-induced secretin release and in
      pancreatic secretion stimulated by luminal factors. The regulation of pancreatic
      exocrine secretion by purines, nitric oxide, and gamma-aminobutyric acid as well
      as by the neuropeptides pituitary adenylate cyclase-activating peptide, gastrin
      releasing peptide, and substance P is reviewed. The role of the central nervous
      system in modulating pancreatic secretion is also described. This review
      highlights the recent advances in knowledge of the neurohormonal regulation of
      pancreatic exocrine secretion.

PMID- 17033331
TI  - Genetics and pancreatic disease.
AB  - The recognition that variations in the DNA sequence of key genes predispose
      individuals to acute pancreatitis, chronic pancreatitis, and pancreatic cancer
      represents one of the greatest breakthroughs in pancreas research. This review
      highlights recent progress in understanding mutations in the cationic trypsinogen
      gene, the pancreatic secretory trypsin inhibitor gene, and the cystic fibrosis
      transmembrane conductance regulator gene with respect to pancreatitis. It also
      notes progress in the use of microarray technology, classification of chronic
      pancreatitis, and predisposition to pancreatic cancer.

PMID- 17033332
TI  - Acute pancreatitis.
AB  - Acute pancreatitis begins as acute pancreatic injury and may generate a systemic
      inflammatory response that evolves into multiorgan failure, leading to death.
      Multiple inciting factors such as toxins (alcohol), gallstones, or endoscopic
      retrograde cholangiopancreatography result in a cascade of events beginning with
      the intra-acinar activation of zymogens and the release of cytokines and other
      proinflammatory mediators. Their release is a major determinant of the systemic
      inflammatory response and distant organ failure. Attempts to attenuate the
      severity of acute pancreatitis by blocking specific inflammatory mediators have
      had limited success. This review is divided into experimental acute pancreatitis
      and clinical acute pancreatitis. The distinction is maintained because although
      animal models of disease have helped define the pathogenesis of acute
      pancreatitis, they do not completely reproduce the clinical syndrome of human
      acute pancreatitis or guarantee equal success of therapies in humans.

PMID- 17033333
TI  - Chronic pancreatitis.
AB  - The pathogenesis of idiopathic chronic pancreatitis remains poorly understood
      despite the high expectations for ascribing the pancreatic damage in affected
      patients to genetic defects. Neither mutations in the cationic trypsinogen gene
      nor mutations of the cystic fibrosis conductance regulator gene account for the
      chronic pancreatitis noted in most patients with idiopathic chronic pancreatitis.
      Attempts to find an autoimmune basis for the pancreatitis in these patients have
      not been very successful. The diagnosis of small duct idiopathic chronic
      pancreatitis remains a great source of frustration for clinicians. Such patients
      with negative results of radiographic studies often cannot be diagnosed unless a
      hormone stimulation test such as a secretin test is performed. Although the
      porcine biologic form of secretin, which has been used to diagnose chronic
      pancreatitis, became unavailable because of widespread use in the treatment of
      children with autism, a synthetic form of porcine secretin has now been approved
      by the US Food and Drug Administration and is available. The true value of
      endoscopic ultrasonography in diagnosing small duct chronic pancreatitis remains
      to be fully defined. Endoscopic ultrasonography is becoming the test of choice in
      detecting radiographic abnormalities in both the parenchyma and ducts of the
      pancreas. Endoscopic ultrasonography-guided celiac plexus block can be performed
      relatively easily and very safely. It can provide excellent short-term pain
      relief in some patients, but reliable predictors of which patients will be
      successful with this therapy are not yet available. Because long-term follow-up
      data on the use of endoscopic ultrasonography in this respect are not available,
      and because the pain of chronic pancreatitis is, indeed, chronic, the role of
      endoscopic ultrasonography-guided celiac plexus block should be limited to
      treating those patients with chronic pancreatitis whose pain has not responded to
      other modalities.

PMID- 17033334
TI  - Pancreatic cancer research: challenges, opportunities, and recent developments.
AB  - Advances in the scientific knowledge and medical management of pancreatic cancer
      are lagging behind significant discoveries in other tumors. From 2001 to 2002,
      the period covered by this review, few but yet important findings have continued
      to push this field of medicine ahead. However, the most promising advance made in
      pancreatic cancer is the increased awareness of this disease by private and
      federal agencies as well as the population at large. In addition, there has been
      a remarkable increase in scientific communication among different research groups
      around the country. National cooperation among government, philanthropic
      organizations, advocacy groups, and scientists offers for the first time a
      framework of hope regarding the establishment of a comprehensive plan to fight
      this dismal disease. Scientists have responded with renewed enthusiasm, which has
      resulted in significant advances in two exciting areas of wide interest in the
      field-genetic animal models and postgenomic mechanisms of pancreatic
      carcinogenesis. The questions that these studies address and their potential
      impact on this field of research are highlighted here.

PMID- 17033335
TI  - Pancreatic surgery.
AB  - Over the past year considerable progress has been made in the field of pancreatic
      surgery. Innovative diagnostic techniques continue to improve the preoperative
      staging of pancreatic cancer. For patients with cancer and biliary obstruction,
      preoperative biliary stenting appears to increase the incidence of wound
      infection after pancreatoduodenectomy but has no effect on other perioperative
      complications. New information about the molecular biology of pancreatic cancer
      may begin to influence the surgical approach to the disease. More cases of
      intraductal papillary mucinous neoplasms are being diagnosed and studied. The
      impact of adjuvant chemotherapy and chemoradiation on survival has been more
      clearly defined in a large, randomized trial. In patients with sterile acute
      necrotizing pancreatitis, conservative nonsurgical management has continued to
      produce favorable results. For chronic pancreatitis, surgery appears to diminish
      both chronic pain and recurrent episodes of acute pain.

PMID- 17033336
TI  - Endoscopic ultrasound of the pancreas: tissue acquisition and intervention.
AB  - Endoscopic ultrasound is an established modality for staging gastrointestinal and
      pancreatic malignancies. Since the development of the linear array echoendoscope,
      the field of interventional endoscopy has continued to evolve as an adjunctive
      method to standard endosonography. The ability to sample extraluminal lesions or
      lymph nodes has overcome the initial limitations of endoscopic ultrasound and
      provided a list of attractive endoscopic ultrasound-guided therapeutic
      applications.This review focuses on recent advancements in the field of
      interventional endosonography related to the diagnosis and therapy of pancreatic
      diseases. In particular, the article reviews the role of endoscopic ultrasound
      guided fine-needle aspiration in diagnosing various pancreatic diseases; the role
      of endoscopic ultrasound-guided fine-needle injection in delivering neurolytic,
      chemotherapeutic, or biologic agents; and emerging procedures like endoscopic
      ultrasound-assisted biliary bypass in the setting of malignant biliary
      obstruction.

PMID- 17033337
TI  - Gastrointestinal epithelial dysplasia: detection with new endoscopic techniques.
AB  - Endoscopic detection of dysplasia currently requires either the presence of a
      visible lesion (such as a polyp) or the serendipitous sampling of a dysplastic
      focus during "blind" surveillance biopsies. To accurately and efficiently examine
      large areas of mucosa during surveillance endoscopy, new methods are required to
      render dysplasia visible. Spectroscopy and optical coherence tomography are two
      technologies under active investigation for this purpose. This review presents
      the basic concepts behind these technologies and discusses their utility in the
      detection of gastrointestinal dysplasia.

PMID- 17033338
TI  - Endoscopic treatment of early gastroesophageal malignancy.
AB  - With the routine use of endoscopy, gastroesophageal cancers, which were often
      diagnosed in the symptomatic and incurable state, are now being diagnosed at
      earlier stages. Treatment of early-stage upper gastrointestinal cancers has
      evolved tremendously. Endoscopic therapy has been employed for early-stage
      lesions in an attempt to avoid the high morbidity and mortality associated with
      current curative procedures such as esophagectomy. These new endoscopic
      techniques include endoscopic mucosal resection, photodynamic therapy,
      electrocoagulation, and laser therapy. Exciting and novel endoscopic therapeutic
      options in diagnosing and treating early gastroesophageal cancers are the focus
      of this review.

PMID- 17033340
TI  - Bibliography current world literature. Pancreas.

PMID- 17033339
TI  - Colon cancer screening strategies.
AB  - Screening has been shown to reduce morbidity and mortality related to colorectal
      cancer. However, the optimal strategy for population screening for colorectal
      cancer has been a topic of heated debate. Recent studies have challenged the
      efficacy and cost-effectiveness of current population screening practices. Novel
      approaches to improve the assessment of an individual's colorectal cancer risk
      and advances in technology are changing our approach to colorectal screening.
      This review covers current guidelines for screening for colorectal cancer, recent
      advances in cancer risk assessment, and the role of endoscopy, virtual
      colonoscopy, and fecal DNA testing in colorectal cancer screening.

PMID- 17033341
TI  - Stomach and duodenum.

PMID- 17033342
TI  - Gastric secretion.
AB  - Overlapping neural, hormonal, and paracrine pathways finely regulate gastric acid
      secretion. In rats and guinea pigs, most of the intrinsic neural innervation to
      the gastric mucosa originates in the myenteric plexus. In contrast, human
      stomachs have a clearly defined submucosal plexus that contains a variety of
      transmitters including nitric oxide, vasoactive intestinal peptide (VIP), gastrin
      releasing peptide (GRP), substance P, and calcitonin gene-related peptide (CGRP).
      Although GRP is known to participate in meal-stimulated acid secretion by
      releasing gastrin in a variety of laboratory animals, recent studies were unable
      to demonstrate a role for endogenous GRP in meal-stimulated gastrin secretion in
      humans. Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of
      the secretin-glucagon-VIP family, has been localized to gastric mucosal neurons
      and may participate in vagally mediated acid secretion. Two novel peptides,
      ghrelin and leptin, have been localized to the stomach. Peripheral administration
      of ghrelin stimulates and of leptin inhibits acid secretion. The binding of
      secretagogues to parietal cells generates changes in second messengers that
      regulate the translocation and activation of the proton pump, HK-ATPase. In
      resting cells, HK-ATPase is contained within cytoplasmic tubulovesicles in an
      inactive form. At stimulation, the tubulovesicles fuse with the apical canaliculi
      and the HK-ATPase is incorporated into the apical membrane where it actively
      pumps H ions in exchange for K. Acute infection with Helicobacter pylori results
      in hypochlorhydria, whereas chronic infection can cause either hypo- or
      hyperchlorhydria, depending on the distribution of the infection and the degree
      of corpus gastritis. Recent studies suggest that inflammatory cytokines, produced
      in response to the organism, can play a role in the perturbations in acid and
      gastrin secretion induced by H. pylori.

PMID- 17033343
TI  - Gastroduodenal mucosal defense: an integrated protective response.
AB  - The mechanisms by which the gastroduodenal mucosa maintains viability and normal
      functioning despite its intensely caustic environment have puzzled clinicians and
      investigators alike for at least 150 years. Protective mechanisms have been
      divided into three main categories: preepithelial (mucus and bicarbonate
      secretion), epithelial (cellular buffering, mucosal architecture and
      permeability), and postepithelial mechanisms (mucosal blood flow). Within each
      category are many other factors that bear on the ability of the mucosa to
      withstand constant changes of luminal pH. We will summarize some of the recent
      findings that pertain to the nature and regulation of these defense mechanisms in
      the context of a historical overview. Therapeutic implications of these findings
      will also be presented in the discussion of novel antiinflammatory compounds
      designed to upregulate simultaneously several defensive mechanisms, with the
      expectation that gastroduodenal damage will be minimized.

PMID- 17033344
TI  - Nonsteroidal antiinflammatory drugs and the stomach.
AB  - We review papers on nonsteroidal antiinflammatory drugs (NSAID) and the stomach
      published in the 12 months ending April 2002. During this period, some further
      developments occurred in the ongoing search for safer antiinflammatory drugs. The
      highly selective COX-2 inhibitors (COX-2i) have again exhibited some toxicity in
      animal models of repair, but continue to seem a safer alternative than
      nonselective inhibitors from the standpoint of the production of human ulcers.
      Some data on the gastrointestinal safety of valdecoxib and parecoxib are
      available, while co-therapies with acid suppressants to reduce the risk of
      conventional NSAID also remain an option (a study comparing lansoprazole with
      misoprostol is now published). Whether co-prescribing a proton pump inhibitor
      with a COX-2i in patients at higher risk is effective or justified awaits the
      results of yet to be completed studies. The nitric oxide (NO)-donating NSAID and
      NO-donating aspirin show some distinct promise in animal studies and early-phase
      clinical trials.

PMID- 17033345
TI  - Peptic ulcer disease.
AB  - The introduction of the "Maastricht 2-2000" document provides some guidance with
      regard to the management of Helicobacter pylori infection in both primary and
      specialist practice settings, albeit primarily in the European setting. The
      putative role of H. pylori in gastric carcinogenesis was supported by a further
      study. Studies on the natural history of peptic ulcer disease (PUD) highlight the
      particular vulnerability of the elderly patient to PUD and its complications, and
      focus attention on targeted intervention in this group, particularly the
      avoidance of nonsteroidal antiinflammatory drugs (NSAID). Little has evolved with
      regard to the introduction of new NSAID, but reports indicate the potential
      association of cyclooxygenase-2 (COX 2)-selective agent use with an increased
      risk of cardiovascular events. The role of H. pylori and NSAID as risk factors
      for peptic ulcer disease and its complications is again explored, and both meta
      analysis and clinical studies provide some evidence of their synergistic effect.
      The introduction of esomeprazole, the S-isomer of omeprazole, has widened the
      clinician's therapeutic choice; the true value of this agent remains to be
      determined.

PMID- 17033346
TI  - Interventional endoscopy.
AB  - Technologic milestones have been achieved in the field of interventional
      endoscopy. These have resulted in improved hemostasis, more accurate cancer
      staging, safer and less invasive methods of removing gastric neoplasms, and
      endoscopic palliation of malignant gastric outlet obstruction via stenting.
      However, just as these milestones are achieved, new challenges emerge: (1) How
      much sedation can one use safely? (2) What is the risk of transmitting infection
      and how can that be prevented? (3) Can scopes be made smaller and more
      comfortable? (4) Can optics be improved? (5) Can endoscopic repair of gastric
      perforations be safely performed? In this section, we review some of these
      issues. First, we will provide an update on the most recent concepts in the field
      of light sedation and infection control. Then, a review of the most commonly used
      interventional endoscopy procedures, including hemostasis, endosonography,
      endoscopic mucosal resection, stenting, and percutaneous gastrostomy tube
      placements. Finally, an overview of the ongoing research and development in the
      field of interventional endoscopy and how it can improve patient comfort,
      diagnostic accuracy, therapeutic efficacy, and training in the future.

PMID- 17033347
TI  - Gastric surgery.
AB  - Most significant research relating to gastric surgery in the past year has
      centered on surgery for gastroesophageal reflux disease (GERD). Antireflux
      surgery has become more popular with advanced laparoscopic technology. Two
      previously accepted surgical principles have been challenged by current studies:
      the importance of division of the short gastrics and the dictum that partial
      fundoplication is preferred for patients at risk for dysphagia. Additionally,
      risk factors for postoperative dysphagia have been identified, allowing for
      better patient selection and education. Further study on the cause of GERD has
      shown a positive correlation between pathologic gastroesophageal reflux and those
      with hiatal hernia or disordered esophageal peristalsis, although cause or effect
      has not yet been established. Literature relating to bariatric surgery has
      confirmed the safety and efficacy of the laparoscopic Roux-en-Y gastric bypass,
      and several papers address the appropriateness of prophylactic cholecystectomy in
      these patients. The role of laparoscopic surgery for treatment of perforated
      peptic ulcer disease has now been validated, with subsequent eradication of
      Helicobacter pylori infection. The relationship of H. pylori infection to acutely
      bleeding ulcers is less clear. Indications for ulcer surgery are predominantly
      limited now to perforation and bleeding because of the availability of effective
      acid-reducing medications and recognition of the role of H. pylori infection.

PMID- 17033348
TI  - Pediatric disorders of the stomach.
AB  - Disorders of the stomach represent a significant portion of the practice of
      pediatric gastroenterology. Controversy still exists in the appropriate
      management of children with abdominal pain and vomiting and large gaps remain in
      our understanding of the physiology and pathophysiology of the stomach in
      children. Nevertheless, we have made significant progress in understanding
      Helicobacter pylori infection and gastric motility in the pediatric population.

PMID- 17033349
TI  - Immunology.

PMID- 17033350
TI  - Immunologic basis for diarrhea.
AB  - Diarrhea is a common sequela of deregulated immune pathways underlying the wide
      range of intestinal acute and chronic diseases. The ongoing investigation of
      novel immune components and susceptibility factors allows better understanding of
      these pathologic mechanisms and continues to advance therapeutic options.

PMID- 17033351
TI  - Toll-like receptors and gastrointestinal diseases: from bench to bedside?
AB  - The family of Toll-like receptors (TLRs) plays a key role in mediating innate
      immune responses to numerous luminal commensal- and pathogen-derived pattern
      molecules by the intestinal mucosa. Recent findings have identified several
      ligands recognized by TLRs as well as the complex downstream signaling effects
      resulting from activation of these receptors. Understanding is emerging of the
      importance of TLRs in mucosal host defense-potentially triggering
      gastrointestinal diseases.

PMID- 17033352
TI  - Revisiting the "hygiene hypothesis" in gastrointestinal allergy.
AB  - The "hygiene hypothesis" in its original form hypothesized that infection in
      early childhood acquired through unhygienic contact with siblings or the mother
      may prevent the development of allergic disease. Several recent epidemiologic
      surveys showing an inverse relationship between the frequency of infectious
      disease and the incidence of allergic diseases lend support to this hypothesis.
      Allergen sensitization of the immune system can occur early in utero against a
      background of neonatal commitment to a Th2 immune response involving the
      production of Th2 cytokines (eg, interleukin (IL)-4, IL-5, IL-13) that are the
      principal mediators of allergic inflammation. Continued allergen exposure is
      associated with predominantly CD4+ Th2 cell proliferation but does not exclude a
      minor Th1 allergen-specific subpopulation that can be further expanded
      nonspecifically and polyclonally by microbial superantigens or as bystanders, by
      interferon-gamma (IFN-gamma) and IL-2 released from Th1 effectors responding to
      antigens associated with infectious pathogens. Th1 cytokines can also subvert
      allergen-specific Th2 lymphocytes to become allergen-specific Th1 cells-a process
      reminiscent of the increased tendency of the maturing immune system of growing
      adults to mount a Th1 response to some environmental and dietary antigens. Unlike
      Th2 cytokines, IFN-gamma and IL-2 inhibit B-cell production of IgE and, hence,
      delimit the capacity of mast cells to degranulate and release allergenic
      mediators. The ability of infectious agents through their danger signals to
      initiate a Th1 response that deviates the Th2 allergenic bias is the basis of the
      hygiene hypothesis.

PMID- 17033353
TI  - T helper cell subclasses and clinical disease states.
AB  - The functionally different CD4 T helper cell subsets known as T helper 1 (Th1)
      and T helper 2 (Th2) display a unique and different cytokine profile. Abnormal
      skewing toward Th1 or Th2 cells has been suggested to play an important role in
      the pathogenesis of autoimmune disorders and in inflammatory and allergic
      diseases. The Th1/Th2 paradigm continues to serve as a model to understand the
      pathogenesis of several pathologic conditions and provides the rationale for the
      development of new strategies for treating and preventing these diseases. Over
      the past year, efforts have continued to increase our understanding of the
      mechanisms underlying the development and regulation of Th cells and their
      pathogenic role and therapeutic potential in the induction and treatment of
      clinic diseases. Several teams of researchers have further examined the
      association of Th1/Th2 inducing factors and allergic disease and intestinal
      inflammatory diseases. The protective effect of helminth infection on allergy and
      the role of regulatory T cells in both Th1- and Th2-mediated diseases have been
      further examined.

PMID- 17033354
TI  - Protective nutrients.
AB  - Recognition that specific nutrients can be beneficial when consumed in amounts
      above the accepted daily requirements has provided a major impetus for the
      critical examination of dietary approaches with single or multiple nutrient
      supplements chosen to modulate the inflammatory response, enhance immune
      function, or improve the blood-gut barrier. Patients suffering the effects of
      hypercatabolism caused by surgery, cancer, or extensive burns are prime
      candidates for immunonutrition, as the intervention has come to be known, as are
      immunosuppressed patients with the human immunodeficiency virus or other
      overwhelming infections. This review focuses on key nutrients used in clinical
      trials for which a body of information on the mode of action and metabolic
      pathways is available. The topics covered include the amino acids, glutamine and
      arginine; omega-3 fatty acids, eicosapentaenoic acid and docosahexanoic acid;
      vitamin A; and zinc. Lastly, we address the area of pre- and probiotics and how
      "friendly" microorganisms are being incorporated into therapeutic regimens aimed
      at sustaining health. The use of immunonutrition requires judicious consideration
      of the potential undesirable effects of certain additives in clinical settings
      where enhanced immune responsiveness can translate into tissue damage and altered
      mucosal defenses.

PMID- 17033356
TI  - Bibliography current world literature. Stomach and duodenum.

PMID- 17033355
TI  - Update on cancer vaccines.
AB  - The development of vaccines to induce tumor-specific immunity in patients with
      cancer has as emerged as a major area of investigation. The identification of
      antigens uniquely expressed by tumor cells and a heightened understanding of
      tumor immunology have resulted in efforts to activate host immunity to recognize
      and reject tumor cells. Tumor-associated antigens and peptides, genes encoding
      tumor antigens, and modified whole tumor cells have been used in preclinical
      studies with provocative results. Potent antigen-presenting cells, known as
      dendritic cells, have also been modified using peptides, genetic material, or
      whole tumor cells to present tumor antigens in the context of co-stimulation to
      overcome tolerance and induce tumor-specific cell killing. Promising data
      generated from the preclinical evaluation of cancer vaccines have resulted in the
      initiation of clinical trials to define the associated toxicity profile,
      immunologic response, and clinical impact of this treatment approach. We
      summarize the preclinical and clinical experience in this expanding area of
      investigation. Cancer vaccines hold much promise; however, many unresolved
      questions remain in the effort to generate a clinically meaningful treatment
      strategy.

PMID- 17033357
TI  - HIV infection and AIDS.

PMID- 17033358
TI  - The role of behavioral research in HIV/AIDS prevention.
AB  - Behavioral and social research has been at the core of HIV/AIDS prevention
      efforts, by identifying the factors that contribute to the risk of transmission
      and by developing effective behavioral interventions to modify that risk. The
      historical focus of behavior-change strategies on decision-making processes
      within the individual has evolved to include more attention to the dynamics of
      interpersonal relationships and the sociocultural contexts in which HIV-related
      risk behaviors occur.

PMID- 17033359
TI  - Recent findings about the heterosexual transmission of HIV and AIDS.
AB  - Study of the heterosexual transmission of HIV has shifted focus from the
      behavioral and demographic risk factors associated with HIV to the biological and
      molecular factors. Although factors such as genetic predisposition may be
      immutable, others such as co-infection with sexually transmitted diseases are
      modifiable by the use of treatment. The effect of antiretroviral treatment is
      also promising but deserves more study, as does the use of contraception and
      microbicides (chemical barriers meant for intravaginal use).

PMID- 17033360
TI  - The HIV epidemic in Italy.
AB  - The implementation of surveillance systems for HIV and of large cohort studies
      have allowed for the construction of models that more accurately describe the HIV
      epidemic. This review focuses on changes in the epidemiological pattern, and the
      effect of changes in behaviour and of antiretroviral therapy.

PMID- 17033361
TI  - Immunizations during HIV infection.
AB  - The safety and efficacy of immunizing HIV-infected persons for other diseases has
      been controversial. Transient increases in HIV viral load have been reported in
      some but not all studies of immunization, and are unlikely to have adverse
      clinical consequences, particularly in the era of more active antiretroviral
      therapy. Although the serological response to immunization is reduced in the HIV
      infected host, recent data suggest that it has some clinical efficacy.

PMID- 17033362
TI  - AIDS oncology.
AB  - New diagnostic approaches to primary central nervous system lymphoma have been
      developed that may make brain biopsy unnecessary in many instances. Reduced-dose
      chemotherapy for non-Hodgkin's lymphoma has been shown to be advantageous in a
      randomized controlled trial. New agents for the treatment of Kaposi's sarcoma are
      available. Adoptive cellular immunotherapy has been shown to be effective in the
      treatment and prevention of Epstein-Barr virus-associated B-cell lymphomas in
      bone marrow transplant recipients, and may have promise in AIDS patients.

PMID- 17033363
TI  - Sexually transmitted diseases and urinary tract infections.

PMID- 17033364
TI  - Subclinical herpes virus reactivation and latency.
AB  - Although there has been considerable refinement in our understanding of the
      processes underlying the establishment and maintenance of latency, important
      research questions remain. Results from various workers imply that the
      establishment of latency may be a dynamic process and may offer possible
      therapeutic targets. The role played by the latency-associated transcripts appear
      to be important in both establishing latency and in aiding reactivation. Recent
      work has shown that reactivation in vivo is much more frequent than previously
      thought and leads principally to subclinical viral shedding. Factors influencing
      subclinical shedding for most patient groups and the response and limitation of
      therapy have been clearly determined.

PMID- 17033365
TI  - Chlamydia immunology.
AB  - Chlamydia trachomatis infection elicits both antibody and cell-mediated immune
      responses. Neutralizing antibody is serovar-specific and dependent upon
      conformational epitopes. CD4 lymphocytes (predominantly type 1 helper T cells)
      function in protection, but the role played by CD8 lymphocytes in protection or
      pathology is less well defined. Local cytokine induction is correlated with
      inflammation and effector influx, and may direct the acquired immune response.

PMID- 17033366
TI  - Genotyping of Neisseria gonorrhoeae.
AB  - Genotyping of Neisseria gonorrhoeae has proved highly discriminatory. It has been
      used to differentiate between isolates of the same serovar, to determine the
      genetic relatedness of antibiotic resistant isolates and to identify isolates
      from sexual contacts. This level of resolution has been possible because
      Neisseria gonorrhoeae exhibits a high degree of genetic variability. The validity
      of using any typing technique to study temporal or geographical differences of an
      organism known to be non-clonal should, however, be carefully considered.

PMID- 17033367
TI  - Ethnicity and sexually transmitted infections.
AB  - Public health workers have long recognized that sexually transmitted diseases are
      differentially distributed within the population, with the highest rates observed
      in ethnic minorities. Incidence rates for bacterial diseases, such as gonorrhea
      and chlamydia, may be five to 10 times higher than in the general population, and
      two to three times higher for prevalent viral infections such as genital herpes.
      Unless ethnic group-specific analyses are performed, however, the elevated rates
      may not be discernible. These groups are also often at highest risk for
      heterosexual HIV transmission. Understanding the differential risks faced by
      ethnic groups is a critical component of developing appropriate behavioral and
      healthcare access interventions.

PMID- 17033368
TI  - Epidemic syphilis in the newly independent states of the former Soviet Union.
AB  - Major syphilis epidemics are occurring in the former Soviet Union as a result of
      the effects of rapid political, economic and social reform on clinical services
      and sexual behaviour. Together with epidemics of injecting drug use-associated
      HIV infection, they pose a major threat of large sexually transmitted HIV
      epidemics. Economic realism demands that control efforts address the market and
      ideological forces driving the development of interventions, as well as technical
      aspects of their design.

PMID- 17033369
TI  - Prospects for human papillomavirus vaccine development: emerging HPV vaccines.
AB  - This review concentrates on recent advances in human papillomavirus vaccine
      development. Strategies for prophylactic HPV subunit vaccines utilizing
      recombinantly synthesized, immunogenic virus-like particles are discussed.
      Therapeutic strategies focusing on the induction of cell-mediated immunity and
      gene manipulation for the treatment of established HPV-associated disease are
      also reviewed.

PMID- 17033370
TI  - Complicated urinary tract infection.
AB  - Urinary tract infection is the second commonest infection encountered in both the
      community and the hospital setting. In order to avoid complications and to
      minimize the unnecessary use of antibiotics, it is essential to have a useful and
      rapid screening test to identify urinary tract infection. The presence of nitrite
      and leukocyte esterase on urinalysis is such a test. Symptomatic bacteriuria
      requires prompt treatment and pyelonephritis should be treated for 10-14 days,
      whereas asymptomatic catheter and non-catheter bacteriuria should not be treated,
      except in the setting of pregnancy and in childhood.

PMID- 17033371
TI  - Skin and soft tissue infections.

PMID- 17033372
TI  - Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, cytokines, growth
      factors and HIV in pathogenesis of Kaposi's sarcoma.
AB  - Epidemiological studies have strengthened the case for Kaposi sarcoma-associated
      herpesvirus/human herpesvirus 8 being the long-sought Kaposi sarcoma agent, but
      have also pointed to a role for other co-factors. Like other tumour viruses,
      Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 establishes a latent
      (persistent) infection in Kaposi sarcoma-spindle (tumorous) cells, but can also
      undergo lytic replication in these and other cell types. Several latent and lytic
      viral genes may play a role in the pathogenesis of Kaposi's sarcoma. Although
      Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 contains at least two
      genes with transforming properties, it has not yet been shown to be oncogenic in
      animals. This, and other studies on inflammatory/angiogenic cellular and viral
      cytokines as well as HIV-Tat, emphasizes the multifactorial complexity of the
      pathogenesis of Kaposi's sarcoma.

PMID- 17033373
TI  - Cutaneous parasites.
AB  - Recent developments in leishmanial research include better survey procedures to
      determine risk factors in the community. Community-based scabies control is seen
      as the only way to reduce the morbidity caused by this infection in developing
      countries. The diagnosis of both infections, and of head lice, however, continues
      to provide problems for the physician.

PMID- 17033374
TI  - Skin, hair and nail fungal infections.
AB  - Fungal infections of the skin, hair and nails are among the most common skin
      diseases. The increased incidence of these infections in recent years has been
      attributed to the large number of immunocompromised patients, life-style changes
      (greater attendance at gymnasiums, public baths, etc.), the use of
      chemotherapeutic agents, and the greater presence of elderly people in the
      general population. Superficial fungal infections were also the most frequent and
      troublesome dermatological condition occurring among US forces during the war in
      Vietnam.

PMID- 17033375
TI  - Dermatological infections in the immunocompromised host.
AB  - The data from the most recent studies concerning infection with human herpes
      virus 8 strongly support a pathogenic role for this virus in the tumoral
      hyperplasia which is a feature of Kaposi's sarcoma. The results from the first
      studies of the sensitivity of human herpes virus 8 to antiviral drugs were also
      published last year. This review also concerns bacterial and mycobacterial
      infections showing unusual presentation, important trials in the prevention of
      infection with varicella zoster virus by using vaccination in children with
      leukemia, and a controlled therapeutic study in HIV-infected patients presenting
      with early syphilis.

PMID- 17033376
TI  - Skin and soft tissue infection: necrotizing fasciitis.
AB  - The incidence of necrotizing fasciitis has increased in the past decade as a
      result of the resurgence severe group A streptococcal infection. Mortality has
      remained unchanged over the past 60 years, supporting the notion that immune
      modulators, such as intravenous immunoglobulin, are required to alter the
      physiological process during the early stages of infection.

PMID- 17033377
TI  - Respiratory infections.

PMID- 17033378
TI  - New polymerase chain reaction-based diagnostic techniques for bacterial
      respiratory infection.
AB  - Polymerase chain reaction protocols are now available for the diagnosis of all of
      the major bacterial respiratory tract pathogens. Molecular techniques are also
      being used to determine the susceptibility of Streptococcus pneumoniae and
      Mycobacterium tuberculosis. In addition, polymerase chain reaction-based
      diagnosis will find a place in the investigation of the epidemiology of some
      pathogens such as Bordetella pertussis and Chlamydia pneumoniae. The added
      sensitivity will allow the detection of mild or asymptomatic cases or carriers
      who may play a role in sustaining the pathogen in the community.

PMID- 17033379
TI  - Antibiotic resistance in respiratory pathogens.
AB  - Antibiotic resistance in respiratory pathogens has dramatically increased during
      recent years. Resistance to penicillin and multiple antimicrobial agents in
      pneumococci and resistance to ampicillin in Moraxella catarrhalis and Haemophilus
      influenzae, as a result of betalactamase production, have become highly prevalent
      worldwide. The emergence of multiple drug-resistant tuberculosis in different
      countries is of concern, and has become a therapeutic challenge.

PMID- 17033380
TI  - Community-acquired pneumonia in adults.
AB  - Efforts to reduce hospitalization or the length of stay are common topics in
      papers published last year. Chlamydia pneumoniae is now recognized worldwide as a
      common pathogen in community-acquired pneumonia. A great variation in the
      frequency of various pathogens is found in different countries, stressing the
      importance of ascertaining the aetiological and epidemiological situation in each
      respective country.

PMID- 17033381
TI  - Hospital-acquired pneumonia: recent advances in diagnosis, microbiology and
      treatment.
AB  - Nosocomial or hospital-acquired pneumonia occurs frequently, despite preventative
      measures and advances in diagnostic procedures and treatment of this severe
      infection. This article will highlight the recent literature with emphasis on
      significant publications and advances in the area of pneumonia pathogenesis,
      microbiology, diagnosis, and response to antimicrobial therapy.

PMID- 17033382
TI  - Treatment for mycobacterial infections.
AB  - Mycobacterium tuberculosis remains the most important global cause of
      mycobacterial disease in humans. The central roles of consistent delivery,
      adherence to therapy, and built-in audit of practice have recently received heavy
      emphasis in the treatment of M. tuberculosis, particularly in new guidelines from
      the World Health Organization. The management of mycobacterial disease in the
      context of HIV infection continues to pose problems, particularly in resource
      poor settings. The most significant development for the clinical management of
      HIV-associated M. tuberculosis infection in the past year has been the
      establishment of the efficacy of isoniazid monotherapy as preventive therapy,
      after the publication of three new randomized, placebo-controlled trials.

PMID- 17033383
TI  - The diagnosis and management of pleural empyema.
AB  - The diagnosis and management of pleural infection continues to improve steadily.
      Recent advances include: newer, smaller, and more comfortable chest drainage
      catheters; improved pleural pus drainage with the aid of intrapleural
      fibrinolytics; and improved surgical procedures including thoracoscopic surgery.
      The optimal size of chest drainage tube remains a matter of debate, with no large
      data sets available to clarify the optimal tube size. In contrast, there are now
      small controlled trials of sound basic methodology which suggest a therapeutic
      role for both fibrinolytics and thoracoscopy. Studies large enough to establish
      clearly the efficacy and safety of these approaches are now at the planning and
      recruitment stage.

PMID- 17033384
TI  - Generalized infections.

PMID- 17033385
TI  - Escherichia coli O157 and human disease.
AB  - In the 15 years since its discovery, Escherichia coli O157 infection has become
      an important public health problem of the developed world, causing concern not
      only because of its rise in incidence, but also because of the severity of its
      complications. Research is still at an evolutionary phase, often providing more
      questions than answers. The most recent developments in human infection are
      presented in this review.

PMID- 17033386
TI  - Human microsporidioses.
AB  - Recent developments in microsporidiosis research include the increased
      utilization of molecular techniques for the investigation of clinical specimens
      as well as for epidemiological and phylogenetic studies. Special attention is
      given to studies reporting severe disseminated microsporidioses involving most
      organs in AIDS patients, and the increased number of HIV-seronegative and
      immunocompetent individuals with microsporidiosis. The potential efficacy of
      fumagillin (Sanofi Recherche, Gentilly, France) in infections caused by
      Enterocytozoon bieneusi, and the remission of intestinal microsporidiosis in HIV
      infected patients with antiretroviral therapy are also highlighted.

PMID- 17033387
TI  - Ehrlichioses: emerging infections.
AB  - Human monocytic and granulocytic ehrlichioses are emerging tick-borne infections.
      Each is caused by different, but related, obligate intracellular bacteria. Recent
      advances have clarified the classification of these species and progress in
      understanding their pathogenesis has begun. There is, however, still much to
      learn about the clinical spectrum, diagnosis, management, and treatment of these
      unusual infections.

PMID- 17033388
TI  - Bartonella infections: diagnostic and management issues.
AB  - Bartonella species are emerging pathogens. Renewed interest in this group of
      bacteria has been highlighted by the recent description of new species, which are
      pathogenic for humans (Bartonella elizabethae and Bartonella clarridgeae), and
      their association with an increasing number of clinical manifestations, the more
      prevalent being cat scratch disease, bacillary angiomatosis, and culture-negative
      endocarditis.

PMID- 17033390
TI  - Immunity and host response.

PMID- 17033389
TI  - Human T-cell lymphotrophic virus type 1: infections and pathogenesis.
AB  - The number of clinical manifestations associated with human T-cell lymphotrophic
      virus type 1 infection continues to expand, as does the number of regulatory
      genes that human T-cell lymphotrophic virus 1 either transactivates or binds to
      directly. The relationship with the immunogenetics of the host is becoming more
      crucial with specific human leukocyte antigen types determining the risk of
      developing tropical spastic paraparesis/human T-cell lymphotrophic virus 1
      associated myelopathy or adult T-cell leukaemia and lymphoma. Perhaps
      surprisingly, given the complexity of the virus-host interaction and the poor
      response to treatment of human T-cell lymphotrophic virus 1 associated conditions
      so far, a really remarkable response to azathioprine and alpha-interferon is
      reported for patients with adult T-cell leukaemia. Other reverse transcriptase
      inhibitors may also be effective in adult T-cell leukaemia and lymphoma and
      tropical spastic paraparesis/human T-cell lymphotrophic virus 1 associated
      myelopathy, although the fact that adult T-cell leukaemia is a monoclonal
      expansion disease that no longer requires virus replication per se, raises the
      question as to whether or not azathioprine is acting as an anti-cancer agent,
      which was its original role before the anti-HIV screening programme.

PMID- 17033391
TI  - Fc receptor and complement receptor-mediated phagocytosis in host defence.
AB  - In the past few years significant progress in the area of phagocyte biology has
      been made in unravelling the mechanism of phagocytosis. In this review we discuss
      the characteristics and functions of complement and Fc receptors and the role
      they play as bridges between humoral and cellular immunity. We focus on the
      function of these receptors in a comprehensive way and propose a novel model to
      explain the integration of various signals for the optimal functioning of
      phagocytic cells.

PMID- 17033392
TI  - Monocyte deactivation in septic shock.
AB  - Septic shock is a complicated syndrome in which pro-inflammatory and anti
      inflammatory processes are dynamically interconnected and regulated. Central to
      these processes is the monocyte, which produces large quantities of pro
      inflammatory cytokines in the presence of bacterial products. During the course
      of sepsis, the production of compensatory anti-inflammatory mechanisms may
      deactivate monocytes and lead to a state of paralysis. This situation is in fact
      similar but not identical to that known as tolerance, in which normal monocytes
      prechallenged with lipopolysaccharide do not respond to a second challenge of
      lipopolysaccharide. Here, we review some of the cellular mechanisms that may lead
      to monocyte deactivation and discuss the clinical implications they may have.

PMID- 17033393
TI  - Novel therapies in streptococcal toxic shock syndrome: attenuation of virulence
      factor expression and modulation of the host response.
AB  - The systemic manifestations of severe invasive group A streptococcal infections,
      such as streptococcal toxic shock syndrome, are mediated by an overwhelming
      inflammatory response induced by streptococcal superantigens and other virulence
      factors. The high mortality rates associated with streptococcal toxic shock
      syndrome demonstrate a need for better therapy in these diseases. Novel
      strategies to attenuate or prevent streptococcal toxic shock syndrome at
      different stages of illness have been proposed. The most promising therapies
      include agents that by various mechanisms attenuate the inflammatory response or
      the action of streptococcal toxins/superantigens, or both.

PMID- 17033394
TI  - Hepatitis C.
AB  - Hepatitis C virus commonly causes chronic liver disease. Chronicity as a result
      of the failure of T-cell-mediated immunity, liver damage caused by cytotoxic T
      lymphocytes, and the evolution of genetic diversity characterize hepatitis C
      infection. Progression, typically silent, is determined by sex, age, alcohol and
      immune status. Interferon and ribavirin are effective in the substantial minority
      of patients with less advanced fibrosis and lower hepatitis C viral loads.

PMID- 17033395
TI  - Does Chlamydia pneumoniae cause coronary heart disease?
AB  - Evidence continues to accumulate to support a role for Chlamydia pneumoniae in
      the pathogenesis of atherosclerosis, and in particular, coronary heart disease.
      In an analysis of 18 seroepidemiological studies, individuals with high-titer
      antibodies to Chlamydia pneumoniae have at least a twofold or larger odds ratio
      for coronary heart disease compared with seronegative individuals. In addition,
      viable Chlamydia pneumoniae has been cultured directly from atherosclerotic
      tissue, and has been demonstrated by polymerase chain reaction,
      immunocytochemistry, and electron microscopy in nearly 50% of atheromatous
      lesions, but in only 5% of control samples. Chlamydia pneumoniae has been shown
      to infect and reproduce in vitro in human smooth muscle cells, coronary artery
      endothelial cells, and macrophages, and has been shown to induce procoagulant
      activity and platelet adhesion factors known to contribute to the pathogenesis of
      atherosclerosis. Furthermore, Chlamydia pneumoniae has been identified in
      atherosclerotic tissue in two experimental animal models. Finally, two pilot
      antibiotic trials of post-myocardial infarction patients receiving antibiotics
      effective against Chlamydia pneumoniae have demonstrated a fivefold reduction in
      cardiovascular events compared with those patients receiving placebo. Although a
      causal effect has not been proved, the relationship between Chlamydia pneumoniae
      and atherosclerosis continues to grow and to stimulate more definitive studies.

PMID- 17033396
TI  - Experimental treatments of meningococcal sepsis.

PMID- 17033397
TI  - The emerging spectrum of tickborne infections.
AB  - Recent advances in tickborne infections have generally served to reiterate
      existing clinical truisms: most tickborne infections must be diagnosed on
      clinical grounds alone, because laboratory testing is rarely useful in early
      illness; the usual presumptive therapy for treatable tickborne infections is
      doxycycline, which may be used even in childhood; except in very young infants,
      most tickborne infections are tolerated by children, whose outcome is generally
      benign.

PMID- 17033398
TI  - Dengue: a continuing challenge for molecular biology.
AB  - Ten years ago Scott Halstead published a seminal review outlining the challenge
      to science provided by dengue. Our review summarizes recent efforts to meet this
      challenge and discusses the potential practical implications of basic research.
      One major long-term goal is the development of a vaccine, and several different
      strategies are currently being advanced. Clinical studies on dengue continue to
      help physicians make rational choices in disease management.

PMID- 17033399
TI  - Prevention of group B streptococcal infection in neonates.
AB  - Most publications on the subject of group B streptococcus since December 1996
      have concentrated on supporting and to some degree extending our existing
      knowledge of the epidemiology of group B streptococcus and of intrapartum
      antimicrobial prophylaxis, which is the only approach available for reducing the
      incidence of group B streptococcal infection. Of greatest importance clinically
      are the reviews and studies on intrapartum antimicrobial prophylaxis, which
      continue to show that this is a worthwhile intervention as it significantly
      reduces the incidence of early onset group B streptococcal sepsis. The best
      approach to the detection of carriage is also covered, as is the changing
      epidemiology as a result of the implementation of intrapartum antimicrobial
      prophylaxis in some centres. Finally, the prospect of a vaccine is discussed.

PMID- 17033400
TI  - Childhood tuberculosis: advances in immunopathogenesis, treatment and prevention.
AB  - Tuberculosis in childhood is an important cause of mortality worldwide. The
      disease is difficult to diagnose and the underlying immune mechanisms are poorly
      understood. Advances in the application of molecular genetic tools, as
      illustrated by the recent completion of the genome sequence of Mycobacterium
      tuberculosis, provide opportunities for the development of improved diagnostic
      tools and vaccines for tuberculosis. It is important that research efforts in
      this area should include consideration of the unique problems and possibilities
      related to the control of tuberculosis in children.

PMID- 17033401
TI  - A reappraisal of current approaches to the management of fungal infections in
      neutropenic patients.

PMID- 17033402
TI  - Fever associated with chemotherapy-induced neutropenia: a review of current
      therapeutic approaches.
AB  - The numbers of cancer patients subjected to chemotherapy-induced neutropenia
      steadily grows as the new indications for systemic treatment expand. When these
      patients develop fever, or other signs of infection, they must receive immediate
      medical attention. This paper discusses the current therapeutic strategy for
      febrile neutropenia in cancer patients and reviews some of the newer approaches,
      which include empirical monotherapy, outpatient protocols, antibiotic prophylaxis
      and the use of haematopoietic growth factors.

PMID- 17033403
TI  - Infections in solid organ transplant recipients.
AB  - Delineation of the pathogenic potential and assessment of the efficacy of newer
      therapeutic modalities for a number of viruses have been among the more notable
      developments in solid organ transplant infections within the past year. Infection
      caused by the novel herpesvirus, human herpesvirus-6, was proposed to be a
      significant cause of fever of unknown origin and a predictor of subsequent
      cytomegalovirus infection. Interleukin-2-primed isologous T lymphocytes led to
      the complete regression of Epstein-Barr virus-positive post-transplant
      lymphoproliferative disorder. Although interferon-alpha alone was shown to be
      largely ineffective as prophylaxis and treatment for hepatitis C virus hepatitis,
      the combination of interferon-alpha and ribavirin appeared promising.
      Documentation within the past year, however, of lamivudine and famciclovir
      resistance in hepatitis B virus, ganciclovir resistance in cytomegalovirus, and
      azole resistance in Candida, is a sobering reminder that antimicrobial
      prophylaxis must be utilized rationally and selectively.

PMID- 17033404
TI  - Infection in patients with congenital immune deficiencies.
AB  - We review recent developments in the pathogenesis of the major
      immunodeficiencies, the pathogens involved, and new diagnostic and treatment
      options. Early diagnosis and prophylaxis are the mainstays in the current
      management of these immunological disorders. New advances, including the use of
      cytokines and growth factors, molecular diagnosis and a better understanding of
      the immunopathogenesis of infections, are discussed.

PMID- 17033405
TI  - Infections due to the herpesvirus group in immunocompromised patients.
AB  - Herpesvirus infections remain a significant cause of morbidity and mortality in
      iatrogenically immunosuppressed individuals despite the considerable progress
      achieved in recent years by the use of anti-viral drugs. Human cytomegalovirus is
      particularly important in this context and major advances have been made towards
      understanding the basis of cytomegalovirus latency and persistence. At the same
      time efforts continue to develop optimal virus detection in immunosuppressed
      individuals with a view to improving current therapeutic policies, and to define
      the emerging problem of anti-viral drug resistance. Finally, the evidence is
      gathering that the newest additions to the human herpesvirus family, i.e. human
      herpesviruses-6, -7 and -8, are significant pathogens in the immunosuppressed.

PMID- 17033406
TI  - Imaging in the diagnosis of infections in immunocompromised patients.
AB  - Early use of CT and MRI helps to diagnose infection in immuno-compromised
      patients earlier and more precisely. Anti-fungal therapy can now be instituted in
      the knowledge that there is scan proven fungal disease and withheld when scans
      indicate other pathology. The optimal way to utilise these tests is described.

PMID- 17033407
TI  - Unusual infections and new diagnostic methods in the immunocompromised host.
AB  - Over the past year, considerable progress has been made in the understanding of
      the pathogenesis of a variety of infections found in the immunocompromised host.
      Some interesting organisms not previously described in this setting have been
      implicated as being causative of disease. Molecular methods for the detection of
      many organisms increase our ability to diagnose infection in these patients, and
      also make the accurate monitoring of infection during treatment possible.

PMID- 17033408
TI  - Antibiotic resistance--the combat zone.

PMID- 17033409
TI  - Guidelines, policies and the Internet.
AB  - The Internet may become a powerful tool in the implementation of medical
      guidelines, but experience with this new technology is rather limited. Scientific
      assessments of how the Internet may cover the needs of healthcare professionals
      are still not available, but concerns about data reliability and the management
      of information abundance are already being raised.

PMID- 17033410
TI  - Infection control in countries with limited resources.
AB  - Considerable progress has been made in the development of effective hospital
      infection control programs in countries with limited resources, most notably in
      Asia and Latin America. National nosocomial infection surveillance methods are
      now used in a variety of countries, particularly in Brazil, and offer a better
      measure for evaluating the rates of common nosocomial infections and gauging the
      effect of prevention efforts. Extending these achievements to other hospitals
      that presently lack effective programs is an organizational and logistic
      challenge for the future. Newer, daunting problems are the prevention and control
      of antimicrobial resistance and nosocomial transmission of tuberculosis.
      Improvements in the protection of healthcare workers from exposure to bloodborne
      pathogens, research regarding the safety and efficacy of the reuse of single-use
      items, and more practical and affordable methods for sterilization and
      disinfection are needed.

PMID- 17033411
TI  - Semmelweis' sesquicentennial: a little-noted anniversary of handwashing.
AB  - This review describes Semmelweis' achievement 150 years ago. User acceptability
      of hand disinfectants has been improved, but Semmelweis' observation that
      handwashing, in contrast to hygienic hand disinfection, is not always
      sufficiently effective, is not yet generally acknowledged, and the compliance of
      medical personnel to the rules of hand hygiene still remains an educational
      problem to be solved.

PMID- 17033412
TI  - Approaches to the diagnosis and prevention of intravascular catheter-related
      infection.
AB  - Intravascular catheter-related infections remain a significant cause of morbidity
      and mortality despite clear guidelines on insertion and care, which should aid in
      their prevention. New approaches in the diagnosis of these infections, which do
      not require removal of the catheter, and novel technologies, including the
      application of antimicrobial agents to the catheter, have demonstrated some
      degree of success in prevention.

PMID- 17033413
TI  - Surgical site infections: the cutting edge.
AB  - Surgical site infections are common and many are preventable. It is critical to
      understand the factors that influence these infections in order to create
      appropriate strategies to reduce this risk. Recent developments in this area and
      recommendations are presented.

PMID- 17033414
TI  - Novel strategies for the use of antibiotics.
AB  - Recent data have suggested an extension of the use of nasal mupirocin into the
      area of infection prevention in cardiac surgery. Randomized placebo-controlled
      studies of preoperative mupirocin are now required to confirm these results. Two
      randomized controlled studies of either antiseptics or antibiotics impregnated or
      coating central catheters have shown advantages in terms of preventing infection
      compared with placebo. The role played by chlorhexidine-coated peripheral
      catheters is less clear.

PMID- 17033415
TI  - Occupationally acquired infections and the healthcare worker.
AB  - Much of the recent research related to occupational infections in healthcare
      workers has focused on the evaluation of the effectiveness of preventive
      measures, the cost-effectiveness of such measures, and alternative approaches to
      preventing common occupational infections. This article reviews recent
      information on healthcare workers about occupationally acquired diseases and
      considers the risks from unusual or re-emerging pathogens. Among recent advances
      of note are effective post-exposure prophylaxis for HIV, approaches to achieving
      immunity to hepatitis B in vaccine non-responders, better diagnostic tests for
      hepatitis C and improved equipment for preventing blood exposure and
      tuberculosis.

PMID- 17033417
TI  - Malaria in 1998: advances in diagnosis, drugs and vaccine development.
AB  - Malaria threatens almost half the world's population. Although a concerted
      worldwide effort might control this disease, the reality is that inadequate and
      ineffective laboratory diagnosis and treatment conspire in the yearly deaths of
      2,000,000 children from malaria. The failure to institute and implement
      safeguards to maintain the efficacy of new antimalarial drugs is likely to
      accelerate the emergence of untreatable malaria, creating an ominous parallel to
      tuberculosis. There is hope. Field expedient, simple and affordable malaria
      diagnostics are at hand. Artemisinin derivatives remain surprisingly effective
      against the multiply drug-resistant falciparum malaria of southeast Asia, despite
      the widespread and unregulated use of these agents. Human trials have begun of
      WR238605, a promising primaquine replacement that has prophylactic, treatment and
      transmission-blocking potential. After demonstrating unprecedented protection
      against homologous challenge, RTS,S, a new sporozite-based malaria vaccine
      candidate, is now in field trials.

PMID- 17033418
TI  - Sequencing the genome of Plasmodium falciparum.
AB  - Advances in microbial genomic sequencing have the potential to revolutionize the
      control of infectious diseases. Recently, a consortium of researchers and funding
      agencies from the United States and Great Britain have embarked on a project to
      sequence the genome from Plasmodium falciparum, the most important cause of human
      malaria. The Malaria Genome Sequencing Project has reached an important milestone
      with the completion of the entire DNA sequence and annotation of chromosome 2, a
      950 kilobase chromosome of Plasmodium falciparum. This review article will
      provide an overview of the malaria genome sequencing project, highlight progress
      in the field of microbial sequencing, and suggest new directions for future
      malaria research.

PMID- 17033419
TI  - Recent advances in leishmaniasis.
AB  - There has been a rapid increase in the understanding of the mechanisms whereby
      Leishmania infects mammalian hosts and evades the immune response. This, in turn,
      is driving the search for vaccines against leishmaniasis. Leishmaniasis is an
      infection in which the dichotomy between cellular (T-helper cell type 1) and
      humoral (T-helper cell type 2) responses is clearly characterized in murine
      models, but is unclear in humans. The diagnosis of infection may be improved by
      use of the polymerase chain reaction and by serology using a recombinant antigen,
      K39. The therapeutic choice in visceral leishmaniasis is aided by recent studies
      of the lipid-associated amphotericin B drugs and aminosidine (paromomycin).
      Unfortunately, interferon-gamma, allopurinol, and topical aminosidine are all
      less effective treatments than was originally thought.

PMID- 17033420
TI  - Advances in schistosomiasis research.
AB  - This review reports on recent developments in the areas of diagnosis,
      chemotherapy and pathology, where female genital schistosomiasis was recently
      identified as a common cause of morbidity in Schistosoma haematobium-endemic
      areas. As a profound understanding of processes underlying resistance and
      susceptibility to infection as well as pathology is central to schistosomiasis
      control, detailed immunological studies of immunity and granuloma formation
      dominate the discussion. Studies on host genetics, on T-helper cell type 1 or 2
      cytokines as well as on cell types influencing immunity and granuloma formation
      have provided precise information that could be of relevance not only to helminth
      but also to microbial infections involving granulomatous reactions.

PMID- 17033421
TI  - Tropical viral infections.
AB  - This section should be of particular interest to the travel medicine physician as
      it reports many new manifestations of exotic viral infections, both in terms of
      new clinical expression or extension to new geographical territory. Included are
      descriptions of improved diagnostic methodologies for arboviral diseases, a
      discussion of safety issues involving a licensed travel medicine vaccine and a
      randomized placebo-controlled trial of a drug widely prescribed to reduce
      vascular permeability in dengue hemorrhagic fever.

PMID- 17033422
TI  - Molecular and therapeutic advances in the management of chronic hepatitis B and
      C.
AB  - Three hundred million individuals worldwide have persistent hepatitis B virus
      infection with 1-2 million hepatitis B virus-associated deaths per year, and an
      estimated 1% of the world's population are infected with hepatitis C virus.
      Recent advances in molecular biology and host responses have led to an increased
      understanding of hepatitis B and C virus disease and new potential targets for
      therapy.

PMID- 17033423
TI  - Viral gastroenteritis.
AB  - There are many viruses infecting the human gut: some are found to cause acute
      gastroenteritis regularly (although not always) like rotaviruses, enteric
      adenoviruses, small round structured viruses and astroviruses; others enter the
      host via the gut and most often cause systemic infection (entero-viruses,
      parvoviruses); and others are not regularly associated with human disease
      (reoviruses, viruses of the Coronaviridae family). The human gut can also be
      infected directly by HIV and, as a consequence of immuno-suppression, by viruses
      of the Herpesviridae family. Most remarkable during the last one to two years
      were the following results: increasing evidence that a tetravalent rhesus
      rotavirus-based vaccine can prevent severe disease after natural human rotavirus
      infection bringing this vaccine candidate close to approval by the Food and Drug
      Administration, USA; better, although not complete, understanding of correlates
      of protection from rotavirus infection; and fuller comprehension of the genomic
      and antigenic diversity of viruses of the Caliciviridae family infecting man.
      There is still no proficient tissue culture system for the human small round
      structured viruses, hindering the acquisition of basic knowledge of the
      replication of these viruses in the human gut. Except against rotaviruses, there
      are no vaccine candidates against human enteric viruses.

PMID- 17033424
TI  - Bacterial infections of the gut (excluding enteric fever).
AB  - Bacterial enteric infections are still a major cause of morbidity and mortality,
      and many challenges lie ahead in understanding and managing these conditions.
      Clostridium difficile remains the most important nosocomial infection. Antibiotic
      resistance makes the treatment of shigella infections increasingly difficult.
      Molecular and cellular techniques are, however, rapidly expanding our
      understanding of the complexity of the pathogenesis of established and newly
      recognized pathogens.

PMID- 17033425
TI  - Epidemiology, diagnosis and treatment of enteric fever.
AB  - Enteric fever continues to be a common and serious problem worldwide, and the
      need for reliable and cheap alternatives to culture methods for diagnosis
      remains. Epidemics of different strains may coexist in the same geographical area
      and the rapid emergence of resistance to fluoroquinolones, independent of plasmid
      mediated multidrug resistance, means that alternative drugs for chemotherapy are
      also needed.

PMID- 17033426
TI  - Vaccination against bacterial gut infections.
AB  - Recent developments in the field of vaccination against gut-borne bacterial
      illness are reviewed, including the major pathogens such as salmonella, shigella,
      cholera and Escherichia coli. The approaches covered range from immunization with
      killed and live attenuated organisms to genetically detoxified toxin molecules
      and DNA vaccination and transgenic foods. Both homologous and heterologous
      responses to various organisms and vector technologies are discussed in murine,
      bovine and human models, and conclusions are drawn regarding their potential use
      in the development of safe, effective and economically viable vaccines.

PMID- 17033427
TI  - Parasitic gut infections.
AB  - Emerging spore-forming protozoa such as cryptosporidia and microsporidia are
      becoming major public health problems in developing countries as well as in the
      developed world. They are a new addition to an already long list of intestinal
      parasites, but their diagnosis is much more difficult than for well-known
      protozoa and helminths. Fortunately, enzyme immunoassay and polymerase chain
      reaction techniques are becoming available not only for the detection of
      Cryptosporidium parvum and the microsporidia, but also for Entamoeba histolytica
      and Giardia lamblia. These assays are not only increasing the sensitivity of
      detection but are also allowing, for the first time, species differentiation such
      as Entamoeba histolytica/dispar or Encephalitozoon intestinalis/Enterocytozoon
      bieneusi.

PMID- 17033430
TI  - Transjugular intrahepatic portosystemic stent-shunt: technical factors and new
      developments.
AB  - The introduction of expandable metal stents in the mid 1980s led to the
      development of transjugular intrahepatic portosystemic stent-shunt (TIPSS) as we
      know it today. Short-lived detrimental effects on the hyperdynamic circulation in
      cirrhosis accompany the acute reduction in portal pressure following TIPSS
      creation. Caution is needed in patients with cardiac dysfunction or pulmonary
      hypertension. With increasing expertise and careful patient selection, fatal
      procedural complications are rare and TIPSS can even be safely used as a bridge
      to liver transplantation. Shunt insufficiency and hepatic encephalopathy are more
      common following TIPSS. Currently, however, novel approaches to tackling both
      these limitations exist. These include the combination of uncovered TIPSS with
      variceal band ligation, and the introduction of polytetrafluoroethylene covered
      stents. Despite the lack of controlled studies, covered stents are now widely
      used and have the potential to drastically reduce shunt insufficiency, the need
      for long-term shunt surveillance and even hepatic encephalopathy.

PMID- 17033431
TI  - The use of transjugular intrahepatic portosystemic stent shunt in the management
      of acute oesophageal variceal haemorrhage.
AB  - Variceal haemorrhage is a common and serious complication of portal hypertension.
      Endoscopic therapy is successful in the majority in controlling bleeding but in
      those who continue to bleed transjugular intrahepatic portosystemic stent shunt
      is highly effective in achieving haemostasis, although the evidence base that
      this is associated with improved survival is limited. This review discusses
      initial management and then the particular role of transjugular intrahepatic
      portosystemic stent shunt. A management algorithm is proposed. The timing of
      intervention is emphasized and the importance of admission to specialized
      centres. Regional protocols are probably essential for the latter to be organized
      effectively.

PMID- 17033432
TI  - Transjugular intrahepatic portosystemic shunt in the management of ascites and
      hepatorenal syndrome.
AB  - Ascites is the most common complication of liver cirrhosis and when it develops
      mortality is 50% at 5 years, apart from liver transplantation. Large volume
      paracentesis has been the only option for ascites refractory to medical
      treatment. The role of transjugular intrahepatic portosystemic shunt in the
      management of diuretic-resistant ascites has been evaluated in many cohort
      studies and five randomized trials up to now, clearly showing improvement in
      natriuresis and clinical efficacy. It, however, remains unclear how transjugular
      intrahepatic portosystemic shunt affects survival and quality of life, because
      hospital admissions owing to worsening encephalopathy may counterbalance the
      reduced need of paracentesis. What is clear is that the patient selection is
      critical. About 30% of patients with ascites develop hepatorenal syndrome at 5
      years, leading to high mortality in its severe and progressive form. As its main
      pathogenetic factor is derangement of circulatory function owing to portal
      hypertension, these patients may benefit from transjugular intrahepatic
      portosystemic shunt, but this has been shown only in small series, in which
      mortality remains very high, owing to the underlying poor liver function.

PMID- 17033433
TI  - Transjugular intrahepatic portosystemic shunt in the management of Budd Chiari
      syndrome.
AB  - Budd Chiari syndrome presents with a wide range of severity and duration of
      symptoms. Transjugular intrahepatic portosystemic shunt has been used to treat
      selected Budd Chiari syndrome patients for several years. The technique of
      transjugular intrahepatic portosystemic shunt may be more challenging than in
      cirrhosis because of hepatic vein occlusion. Covered transjugular intrahepatic
      portosystemic shunt stents have reduced the requirement for follow-up
      interventions. Transjugular intrahepatic portosystemic shunt has been a
      successful bridge to liver transplant for Budd Chiari syndrome but is the
      definitive treatment in many cases. Patient selection is important to determine
      who will benefit from transjugular intrahepatic portosystemic shunt or other
      treatments such as hepatic vein recanalization or liver transplant.

PMID- 17033434
TI  - Transjugular intrahepatic portosystemic stent-shunt in the management of gastric
      and ectopic varices.
AB  - Uncertainty exists about the ideal therapy for gastric and ectopic varices owing
      to relatively few controlled studies. Endoscopic therapy with tissue adhesives
      and thrombin appear promising. Transjugular intrahepatic portosystemic stent
      shunt has a role in patients with refractory gastric variceal bleeding in the
      presence of a patent portal vein. The addition of coil embolization may be
      particularly useful for ectopic varices, as these can continue to bleed despite
      successful portal pressure reduction. The high efficacy of transjugular
      intrahepatic portosystemic stent-shunt has to be balanced against the potential
      for increased encephalopathy. Balloon occluded retrograde transvenous
      obliteration is a recent technique for patients with gastro-renal shunts and
      large gastric varices. Early results are promising, and balloon occluded
      retrograde transvenous obliteration may be valuable in patients who bleed at
      lower portal pressures, in the encephalopathic patient, or where the portal vein
      is not patent. Its use may be limited by availability or lack of technical
      expertise, and caution is required in patients with large oesophageal varices.

PMID- 17033435
TI  - Miscellaneous indications for transjugular intrahepatic portosystemic stent
      shunt.
AB  - This review will discuss the use of transjugular intrahepatic portosystemic stent
      shunt in a number of relatively uncommon clinical situations. In particular, we
      will focus our paper on the use of transjugular intrahepatic portosystemic stent
      shunt for hepatic hydrothorax, hepatopulmonary syndrome, veno-occlusive disease,
      portal hypertensive gastropathy and gastric antral vascular ectasia, before
      surgery and after liver transplantation.

PMID- 17033436
TI  - Transjugular intrahepatic portosystemic shunt in the prevention of rebleeding in
      oesophageal varices.
AB  - Variceal bleeding is a common complication of cirrhosis and has a high in-patient
      mortality (30-50%). Rebleeding is a major cause of death and occurs in 35% of
      patients at 6 weeks after the initial bleeding episode and 75% at 1 year.
      Therefore, strategies that improve survival by preventing rebleeding in the early
      period are crucial to improve long-term survival. This review concentrates on the
      evidence for transjugular intrahepatic portosystemic shunt in the prevention of
      rebleeding. Transjugular intrahepatic portosystemic shunt in comparison with
      endoscopic and pharmacological therapies is clearly superior at reducing the rate
      of rebleeding in those patients who had an oesophageal variceal haemorrhage. It,
      however, does not improve mortality and is associated with a greater risk of
      encephalopathy and is more costly than endoscopic procedures. It is therefore
      generally used when endoscopic therapy has failed but may be useful in patients
      who would tolerate a rebleed poorly such as Child's C patients. Randomized
      controlled trials are required to evaluate the role of polytetrafluoroethylene
      shunts in the prevention of rebleeding as their improved patency and suggested
      reduced incidence of encephalopathy make them a very attractive potential
      treatment for rebleeding.

PMID- 17033437
TI  - Adult population screening for coeliac disease: comparison of tissue
      transglutaminase antibody and anti-endomysial antibody tests.
AB  - Serological screening tests for coeliac disease have significantly advanced the
      diagnosis of this condition. The very high specificity (almost 100%) of anti
      endomysial antibody detection has been repeatedly confirmed, whereas a lower
      specificity (90-95%) is found with anti-tissue transglutaminase antibody assays.
      In the study by Malekzadeh and colleagues, a group of study participants were
      identified with raised anti-tissue transglutaminase antibodies, but the
      endomysial antibody test was negative in 86%. Although many of these participants
      were found to have raised intra-epithelial lymphocytes in their small intestinal
      mucosa, there is currently insufficient evidence to confidently diagnose gluten
      sensitive disease in these patients. Hence, their report that a minimum
      prevalence of 1:104 of gluten sensitivity is found in the general population of
      Iran is likely to be an over-estimate and requires confirmation.

PMID- 17033438
TI  - Self-expanding stents in oesophageal cancer.
AB  - The main therapeutic concern in patients with inoperable oesophageal cancer is
      palliation of dysphagia. Self-expandable metal stents are widely used because
      they are safer than conventional plastic stents, offer rapid relief from
      dysphagia and may seal off tracheo-oesophageal fistulae. Self-expanding metal
      stents, particularly when uncovered, are, however, associated with the
      disadvantage of tumour ingrowth. Self-expandable plastic stents are entirely
      covered and easy to reposition in case of migration and usually induce less
      inflammatory proliferation at their flanges when compared with metal stents. The
      major disadvantage of the current version of plastic stents is the large diameter
      and stiffness of the stent delivery system when compared with metal stents.
      Therefore, plastic stents are more difficult to place in patients with angulated
      strictures or with tumours located in the cervical oesophagus near the upper
      sphincter.

PMID- 17033439
TI  - Screening of the adult population in Iran for coeliac disease: comparison of the
      tissue-transglutaminase antibody and anti-endomysial antibody tests.
AB  - BACKGROUND AND AIMS: Population-based studies for the prevalence of coeliac
      disease (CD) in west-Asian countries are scarce. We aimed to determine the
      prevalence of gluten-sensitive enteropathy (GSE) in the general population of
      northern and southern Iran, and evaluate the sensitivity and specificity of the
      anti-endomysial antibody (EMA) immunofluorescent test and the enzyme-linked
      immunosorbent assay-based test for determination of the IgA anti-tissue
      transglutaminase antibody (tTG-Ab) using the human recombinant transglutaminase
      antigen for the detection of CD in screening the asymptomatic adult population.
      MATERIAL AND METHODS: Using a stratified random sampling method we enrolled a
      total of 2799 individuals (1438 from Sari and 1361 from Kerman). The mean age was
      33.7 years (range 18-66), with 1398 men. IgA anti-tissue transglutaminase (tTG)
      and IgA anti-EMA were determined in the serum of all subjects. Those participants
      with a positive serology for any of the two tests underwent small intestinal
      biopsy, and were classified according to revised Marsh criteria histologically. A
      diagnosis of GSE was based on positive serology and a compatible
      histopathological finding. The maximum likelihood latent class model was used to
      estimate the sensitivity and specificity of the two tests. RESULTS: Twenty-nine
      cases showed positive IgA tTG-Ab (15 men and 14 women, mean age 35.4 years, range
      18-59), whereas only five were simultaneously positive for EMA. Except for two
      subjects with normal small bowel histology (Marsh 0), all other subjects were
      found to have biopsy findings compatible with GSE: 18 Marsh I, five Marsh II,
      three Marsh IIIa and one Marsh IIIc lesions. he prevalence of GSE was 0.96% or
      1:104. The sensitivity and specificity of the human-recombinant IgA tTG-Ab assay
      were 100 and 99%, respectively, whereas the results for IgA EMA were 19 and 100%,
      respectively. The IgA EMA was positive in cases with advanced mucosal lesions of
      the small bowel. The mean serum value of IgA tTG-Ab was higher in patients with
      severe enteropathy compared with those showing slight mucosal changes (P<0.05).
      CONCLUSION: The minimum prevalence of gluten sensitivity among the general
      population of northern and southern Iran is 1:104. The best screening test for
      the detection of GSE in the general population is IgA tTG-Ab.

PMID- 17033440
TI  - Consumption of gluten-free products: should the threshold value for trace amounts
      of gluten be at 20, 100 or 200 p.p.m.?
AB  - OBJECTIVE: The threshold of gluten contamination in gluten-free products of both
      dietary and normal consumption is under debate. The objective of this study was
      to gather information on consumption of gluten-free products intended for dietary
      use of people under a gluten-free diet. This information is essential to
      ascertain the exposure of coeliac patients to gluten through their diet and
      deduce the maximum gluten content that these products should contain to guarantee
      a safe diet. METHODS: A diet diary of consumption of gluten-free products
      intended for dietary use was distributed to the coeliac societies of two typical
      Mediterranean countries (Italy and Spain) and two Northern countries (Norway and
      Germany). The diet diary included a self-weigh table of the selected food items
      and a 10-day consumption table. Results were reported in percentiles as
      distributions were clearly right skewed. RESULTS: The respondents included in the
      study accounted for 1359 in Italy, 273 in Spain, 226 in Norway and 56 in Germany.
      Gluten-free products intended for dietary use contributed significantly to the
      diet of coeliac patients in Italy, Germany and Norway and to a lesser degree in
      Spain. The most consumed gluten-free product in all countries was bread, and it
      was double consumed in the Northern countries (P<0.001). Mediterranean countries
      showed consumption of a wider variety of gluten-free foods and pasta was eaten to
      a large degree in Italy. CONCLUSIONS: The differences between Northern and
      Mediterranean countries were not in the total amount of gluten-free products but
      in the type of products consumed. The observed daily consumption of gluten-free
      products results in the exposure to rather large amounts of gluten, thus the
      limit of 200 p.p.m. should be revised. A limit of 20 p.p.m. for products
      naturally gluten-free and of 100 p.p.m. for products rendered gluten-free is
      proposed to guarantee a safe diet and to enable coeliac patients to make an
      informed choice. These limits should be revised as new data become available.

PMID- 17033441
TI  - Palliative treatment of esophageal carcinoma with self-expanding plastic stents:
      a report on 69 cases.
AB  - OBJECTIVES: The use of self-expandable plastic stents has offered a reasonable
      alternative of self-expandable metal stents in palliative treatment of esophageal
      malignancies, in the recent years. Studies and clinical data on the use of self
      expandable plastic stents in esophageal cancer are, however, available in a very
      limited number. Here, we present the results of our 3-year study designed to
      evaluate the efficacy of self-expandable plastic stents in palliation of advanced
      esophageal carcinoma. PATIENTS AND METHODS: Between January 2001 and February
      2004, 69 patients with advanced nonoperable esophageal cancer were enrolled in
      the study and followed up until their death, after insertion of Polyflex self
      expandable plastic stents. Dysphagia scores, Karnofsky indices and body weights
      were determined and compared in order to evaluate the effect of the stent
      insertion on general status and well-being of the patients. RESULTS: Insertion of
      Polyflex self-expandable plastic stents and covered self-expandable metal stents
      was performed in 66 cases and in eight cases, respectively; in certain patients,
      owing to complications, more than one stent had to be inserted. In all cases, the
      insertion of stents has been performed without major complication and it has led
      to an instant improvement in swallowing and dysphagia scores. The rates of
      tumoral overgrowth and of stent migration were low. The mean follow-up time of
      our patients was 129 days (10-312 days). CONCLUSION: In concordance with previous
      studies, according to our results, the use of self-expandable plastic stents in
      palliation of esophageal cancer seems to be safe and effective in improving the
      quality of life of these patients.

PMID- 17033442
TI  - Surface area: a better predictor of disease severity than the height and volume
      of the barium column in patients with primary achalasia.
AB  - OBJECTIVE: Subjective assessment of primary achalasia is not accurate. We aimed
      to study the utility of surface area of barium retention in the objective
      assessment of these patients. METHODS: Subjective and objective esophageal
      functions of 99 patients with primary achalasia were evaluated initially and 43
      of them were reevaluated 1 month after balloon dilation. RESULTS: Before
      dilation: Ninety-nine patients were enrolled. Forty-one of them were male. The
      mean age was 37.5+/-15.3 years. The mean score, resting lower esophageal
      sphincter pressure, height, surface and volume of barium retention at 5 min were
      8.03+/-3.1, 59.1+/-20 mmHg, 9.9+/-4.9 cm, and 23.6+/-13.9 cm and 53.2+/-47.7 cm,
      respectively. Surface area at 5 min had best correlation and predictive value for
      resting lower esophageal sphincter pressure. After dilation: Forty-three of 99
      patients were reevaluated after balloon dilation. The mean age was 36.8+/-13.6
      years. Seventeen of them were male. Mean score, resting lower esophageal
      sphincter pressure, height, surface area and volume of barium retention at 5 min
      dropped significantly after dilation. Surface area at 5 min had best correlation
      and predictive value for lower esophageal sphincter pressure. CONCLUSIONS:
      Surface area of barium retention at 5 min is an accurate objective tool to assess
      patients with primary achalasia. It is cheap and easy to perform; therefore, it
      could be used more frequently in postdilation follow-up.

PMID- 17033443
TI  - The pathogenesis of idiopathic megacolon.
AB  - BACKGROUND: Even today, the pathogenesis of idiopathic megacolon is still a
      subject of controversy. Anomalies of the gastrointestinal autonomous nervous
      system or of the smooth muscle of the muscularis propria are being considered.
      METHODS: Sixty-three idiopathic megacolon resections between 1997 and June 2004
      were investigated. The native specimens were coiled caudo-cranially and cryostat
      cut. Connective tissue was stained with picric acid/Sirius red after Delauney
      fixation. Immunohistochemistry was performed for collagen types I, II, III and
      IV, as well as smooth muscle actin, vimentin, desmin fibronectin and CD117 for
      interstitial cells of Cajal. The enteric nervous system was examined by enzyme
      histochemistry for acetylcholine-esterase, lactate dehydrogenase, succinic
      dehydrogenase and nitroxide synthase. RESULTS: Histologically, idiopathic
      megacolon was characterized by a total atrophy of the collagenous tendinous
      connective tissue membrane of the myenteric plexus and the tendinous collagen
      fibre net of the muscularis propria. Immunohistochemically, mainly collagen type
      III was missing in the muscularis propria. Interestingly, the incidence of
      idiopathic megacolon in those of the female sex was seven times more frequent
      than in the male sex. The myenteric plexus was normal in the majority of
      patients. Interstitial cells of Cajal, collagen II and IV, as well as smooth
      muscle actin, desmin and fibronectin showed no consistent alteration. CONCLUSION:
      A normally structured tendinous fibre net of muscularis propria is an essential
      prerequisite for effective gut peristalsis. Atrophy of the tendinous fibre net
      abolishes peristalsis and allows for unlimited distension of the colon. A
      diagnosis of idiopathic megacolon can reliably be made on a collagen stain. The
      normal findings of myenteric plexus support the hypothesis that a primary
      metabolic defect of muscularis propria may be the underlying cause of idiopathic
      megacolon.

PMID- 17033445
TI  - Changing serological status and low vaccination-induced protection rates against
      hepatitis B characterize chronic hepatitis C virus-infected injecting drug users
      in Greece: need for immunization policy.
AB  - OBJECTIVE: To evaluate the serological status of hepatitis B virus infection
      among Greek injecting drug users with chronic hepatitis C virus infection; to
      correlate hepatitis B virus infection status with the possible time of infection
      and the principal genotype of hepatitis C virus infection. METHODS: Two hundred
      and thirty consecutive injecting drug users with chronic hepatitis C virus
      infection were evaluated for serological markers of hepatitis B virus infection.
      One hundred and three of them (44.8%) reported intravenous drug use beginning
      before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical
      analysis of data was based on Student's t-test and chi analyses. RESULTS: Eighty
      five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had
      serological markers of previous hepatitis B virus infection (P<0.001). Eleven
      patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for
      all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients
      and 16.5% (21/127) of group B had vaccination-induced protective antibody levels
      (anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected
      with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B,
      P=0.42). The percentages of patients infected with genotype-1 were also
      comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A
      significantly higher percentage of group A patients were infected with genotype-4
      (19.7%) than those in group B (4.9%, P=0.02). CONCLUSION: The serological profile
      of hepatitis B virus infection among Greek hepatitis C virus-infected injecting
      drug users is changing. The proportion of successfully vaccinated hepatitis B
      virus injecting drug users, although significantly higher than the previous
      decades, is still relatively low. Vaccination policy in this high-risk group for
      viral hepatitis is urgently needed.

PMID- 17033444
TI  - The complementary Erlangen active simulator for interventional endoscopy training
      is superior to solely clinical education in endoscopic hemostasis--the French
      training project: a prospective trial.
AB  - BACKGROUND: The Erlangen Active Simulator for Interventional Endoscopy (EASIE)
      using ex-vivo porcine organs was introduced in 1997. The present study should
      analyze whether repeated EASIE simulator training in endoscopic hemostasis led to
      superior performance compared with a traditionally educated group. The results
      were compared with a similar project in New York. METHODS: Thirty-five French GI
      fellows were enrolled. Baseline skills evaluation was performed in four
      disciplines (manual skills, injection/coagulation, clip application and variceal
      ligation) using the compactEASIE-simulator equipped with an upper
      gastrointestinal organ package for bleeding simulation. The same, translated
      evaluation forms (from the prior New York project) were used. Subsequently,
      fellows were randomized into group A (n=17, only clinical education) and group B
      (n=18, additional three simulator trainings). Group B was trained the next day
      and after 4 and 7 months by experts of the French Society of Gastrointestinal
      Endoscopy. Both groups performed routine and emergency endoscopies at their home
      hospitals during the study period. Both groups were re-evaluated blindly after 9
      months. RESULTS: The learning curve for group B showed a significant improvement
      in all disciplines (P<0.004) whereas group A improved significantly in only two
      of four disciplines at blinded final evaluation (manual skills P=0.02,
      injection/coagulation P=0.013). The direct comparison of groups B and A at
      blinded final evaluation showed significantly superior ratings for group B in all
      disciplines (P<0.006) and significantly shorter performance times in two
      disciplines (P=0.016 each). The comparison with the similar 'New York project'
      revealed that preexisting differences in skills were adjusted by the training.
      CONCLUSION: Complementary trainings (three workshops in 7 months) in endoscopic
      hemostasis using the compactEASIE improved skills compared with a solely clinical
      education. The results of the 'New York project' were confirmed and benefits were
      independent from the medical educational system.

PMID- 17033446
TI  - Anastrozole-induced hepatotoxicity.
AB  - We present a case of hepatotoxicity induced by an aromatase-inhibiting hormonal
      antineoplastic drug (anastrazol) in an elderly woman. This is the first reported
      case in the literature.

PMID- 17033447
TI  - Imatinib mesylate-induced acute hepatitis with autoimmune features.
AB  - Autoimmune hepatitis is a disorder of unknown aetiology. Imatinib belongs to a
      new class of anticancer agents with high selectivity toward a specific molecular
      target. Its main indications are chronic myeloid leukaemia and gastrointestinal
      tumours. We report here, for the first time to our knowledge, imatinib mesylate
      induced hepatitis with autoimmune features.

PMID- 17033448
TI  - Olive oil for symptomatic relief of duodeno-gastro-oesophageal reflux after
      gastrectomy.

PMID- 17033450
TI  - Introduction of the 29th Lauriston S. Taylor Lecturer, John B. Little.

PMID- 17033451
TI  - Lauriston S. Taylor lecture: nontargeted effects of radiation: implications for
      low-dose exposures.
AB  - Traditional thinking has been that the biological effects of ionizing radiation
      occur in irradiated cells as a consequence of the DNA damage they incur. This
      implies that (1) biological effects occur only in irradiated cells, (2) radiation
      traversal through the nucleus of the cell is a prerequisite to produce a
      biological response, and (3) DNA is the target molecule in the cell. Evidence has
      been emerging, however, for non-DNA targeted effects of radiation; that is,
      effects including mutations, chromosomal aberrations, and changes in gene
      expression that occur in cells that in themselves receive no radiation exposure.
      Two of these phenomena will be described in this paper. The first is radiation
      induced genomic instability whereby biological effects, including elevated
      frequencies of mutations and chromosomal aberrations, arise in the distant
      descendants of irradiated cells. The second phenomenon has been termed the
      "bystander effect," whereby in a mixed population of irradiated and nonirradiated
      cells, biological effects arise in those cells that receive no radiation
      exposure. The damage signals are transmitted from cell to cell through gap
      junction channels, and the genetic effects observed in bystander cells appear to
      result from an upregulation of oxidative stress. The possible influence of these
      nontargeted effects of radiation on the response to low-dose exposures is
      discussed.

PMID- 17033452
TI  - Managing the disposition of low-activity radioactive materials. Proceedings of
      the 41st Annual Meeting of the National Council on Radiation Protection and
      Measurements. 2005. Bethesda, Maryland, USA.

PMID- 17033453
TI  - Warren K. Sinclair keynote address: contemporary issues in risk-informed decision
      making on the disposition of radioactive waste.
AB  - A consistent and transparent risk-informed approach to managing nuclear waste is
      plagued with different regulators, different rules and regulations for different
      waste types, different compliance requirements, and indecisions about
      probabilistic vs. deterministic models. Low-activity waste management is
      particularly void of a path forward with respect to being risk-informed. Risk
      assessment is not referenced in the statutes on low-activity waste even though
      both the U.S. Environmental Protection Agency and U.S. Nuclear Regulatory
      Commission (U.S. NRC) have policies to apply consistent risk management
      approaches to all of their programs. The U.S. NRC has developed guidance on the
      preparation of probabilistic performance assessments for low-activity waste
      facilities, but there have been no serious takers and a lack of initiative on the
      part of licensees. Thus, little to no experience exists on risk-informing low
      activity waste. The missed opportunities include establishing a risk basis that
      would allow for simpler, safer, and much less costly alternatives for low
      activity waste disposal while enabling society to have the full benefit of
      radiation technologies. There is hope that congressional action or regulatory
      rule making will address some of these issues with the result being the adoption
      of a more general and unified approach to risk-informed regulation of all types
      of waste. Just as much of the initiative for risk-informed nuclear power came
      from industry, it must also be the case for nuclear waste. A start would be the
      adoption of a basic framework of risk assessment in waste management applicable
      to all types of waste--radioactive and nonradioactive. The "set of triplets" risk
      assessment framework that is applicable to any kind of risk is an established
      alternative. It is believed that such a framework with the support of a
      regulatory structure made compatible through appropriate rulemaking or
      congressional action, and the experience of the probabilistic performance
      assessments for the Waste Isolation Pilot Plant and the proposed Yucca Mountain
      high-level waste repository, could result in the right path forward for the
      regulation and management of low-activity waste.

PMID- 17033454
TI  - Improving the regulation and management of low-activity radioactive wastes.
AB  - This paper summarizes the first phase of a study in progress by a committee of
      the National Research Council's Board on Radioactive Waste Management. The Board
      initiated the study after observing that statutes and regulations administered by
      the federal and state agencies that control low-activity radioactive wastes have
      developed as a patchwork over almost 60 y. These controls usually reflect the
      enterprise or process that produced the waste rather than the waste's
      radiological hazard. Inconsistencies in the regulatory patchwork or its
      application may have led to overly restrictive controls for some low-activity
      wastes while others were neglected in comparison. In the first phase of this
      study, the committee reviewed current low-activity waste inventories,
      regulations, and management practices. This led the committee to develop five
      categories that encompass the spectrum of low-activity wastes and serve to
      illustrate gaps and inconsistencies in current regulations and management
      practices. The committee completed its first phase with four findings that will
      lead into the final phase of the study. This paper is excerpted from the
      committee's interim report that was issued in October 2003.

PMID- 17033455
TI  - Risk-informed radioactive waste classification and reclassification.
AB  - Radioactive waste classification systems have been developed to allow wastes
      having similar hazards to be grouped for purposes of storage, treatment,
      packaging, transportation, and/or disposal. As recommended in the National
      Council on Radiation Protection and Measurements' Report No. 139, Risk-Based
      Classification of Radioactive and Hazardous Chemical Wastes, a preferred
      classification system would be based primarily on the health risks to the public
      that arise from waste disposal and secondarily on other attributes such as the
      near-term practicalities of managing a waste, i.e., the waste classification
      system would be risk informed. The current U.S. radioactive waste classification
      system is not risk informed because key definitions--especially that of high
      level waste--are based on the source of the waste instead of its inherent
      characteristics related to risk. A second important reason for concluding the
      existing U.S. radioactive waste classification system is not risk informed is
      there are no general principles or provisions for exempting materials from being
      classified as radioactive waste which would then allow management without regard
      to its radioactivity. This paper elaborates the current system for classifying
      and reclassifying radioactive wastes in the United States, analyzes the extent to
      which the system is risk informed and the ramifications of its not being so, and
      provides observations on potential future direction of efforts to address
      shortcomings in the U.S. radioactive waste classification system as of 2004.

PMID- 17033456
TI  - Managing the disposition of potentially radioactive scrap metal.
AB  - In 2002, the National Council on Radiation Protection and Measurements (NCRP)
      issued Report No. 141, Managing Potentially Radioactive Scrap Metal. The report
      evaluates management policy and related issues regarding scrap metal generated in
      regulated facilities that have been under radiological control or have
      radiological concerns. It has been estimated that more than 9 million metric tons
      of scrap metal of all types that have been associated with the production or use
      of radioactive materials will be generated during the coming decades at various
      facilities across the United States. Currently, disposition of such metal has
      encountered particular obstacles, primarily because of the lack of a consistent
      disposition policy, systematic regulatory provisions, and, above all, public
      understanding. Without clarity in the regulatory passage, much of the scrap
      metal, including metal that has not been contaminated, could be mischaracterized
      as low-level radioactive waste, resulting in a costly disposition operation. NCRP
      Report No. 141 identifies this general category of metal as "potentially
      radioactive scrap metal" (PRSM) and discusses the viable disposition options for
      facilitating its management. Because much of the PRSM has been found to contain
      very low residual radioactivity or even none at all, one consideration is to
      release such metal outside of the radiological control framework. This would
      require the development and implementation of a set of strict release standards
      in the United States that would necessarily be risk-based and supported by a
      comprehensive management scheme. Developing a policy of this kind, however, would
      entail the resolution of many issues, not the least of which would be public
      acceptance, including that of the metal industry, of the possible recycling of
      PRSM in the general commerce.

PMID- 17033457
TI  - International standards related to the classification and deregulation of
      radioactive waste.
AB  - Although solid radioactive waste management is mainly a national concern, there
      are some aspects that have international implications. One important example is
      the decommissioning of nuclear facilities, which results in the release of
      materials that could be reused and recycled. It is possible that these materials
      could enter international trade, especially if the material is a metal. It is
      clearly desirable, therefore, to have appropriate international standards to help
      regulate trade. This paper describes recent international developments relating
      to the establishment of radiological criteria for the release of materials from
      regulatory control (clearance). There have already been some experiences of
      clearance and the transfer of recycled materials within Europe, and this paper
      reviews that experience. It also discusses recent developments in relation to the
      international classification of radioactive waste.

PMID- 17033458
TI  - The Spanish Protocol for radiological surveillance of metal recycling: a
      collaboration of government and industry.
AB  - The presence of radioactive materials in scrap metal has been detected relatively
      often in recent years. As a result of an accidental melting of a 137Cs source in
      a Spanish steel mill (Acerinox) in 1998, the national authorities, the involved
      private companies, and the main trade unions drafted a protocol for prevention of
      and responding to such events ("Spanish Protocol"). The Protocol was signed in
      1999. The number of subscribing companies is 90. The Protocol is a voluntary
      agreement defining the radiological surveillance of scrap metal and its products
      and the duties and rights of the signatories. From the effective date of the
      Protocol to December 2004, 461 pieces of ferric scrap were detected including
      sources of radiation and contaminated metal. Four melting incidents have happened
      in different companies.

PMID- 17033459
TI  - An industry perspective on commercial radioactive waste disposal conditions and
      trends.
AB  - The United States is presently served by Class-A, -B and -C low-level radioactive
      waste and naturally-occurring and accelerator-produced radioactive material
      disposal sites in Washington and South Carolina; a Class-A and mixed waste
      disposal site in Utah that also accepts naturally-occurring radioactive material;
      and hazardous and solid waste facilities and uranium mill tailings sites that
      accept certain radioactive materials on a site-specific basis. The Washington
      site only accepts low-level radioactive waste from 11 western states due to
      interstate Compact restrictions on waste importation. The South Carolina site
      will be subject to geographic service area restrictions beginning 1 July 2008,
      after which only three states will have continued access. The Utah site dominates
      the commercial Class-A and mixed waste disposal market due to generally lower
      state fees than apply in South Carolina. To expand existing commercial services,
      an existing hazardous waste site in western Texas is seeking a Class-A, -B and -C
      and mixed waste disposal license. With that exception, no new Compact facilities
      are proposed. This fluid, uncertain situation has inspired national level
      rulemaking initiatives and policy studies, as well as alternative disposal
      practices for certain low-activity materials.

PMID- 17033460
TI  - Scrap metals industry perspective on radioactive materials.
AB  - With more than 80 reported/confirmed accidental melts worldwide since 1983 and
      still counting, potential contamination by radioactive materials remains as a
      major concern among recycled scrap and steel companies. Some of these events were
      catastrophic and have cost the industry millions of dollars in business and, at
      the same time, resulted in declining consumer confidence. It is also known that
      more events with confirmed radioactive contamination have occurred that involve
      mining of old steel slag and skull dumps. Consequently, the steel industry has
      since undergone massive changes that incurred unprecedented expenses through the
      installation of radiation monitoring systems in hopes of preventing another
      accidental melt. Despite such extraordinary efforts, accidental melts continue to
      occur and plague the industry. One recent reported/confirmed event occurred in
      the Republic of China in 2004, causing the usual lengthy shutdown for expensive
      decontamination efforts before the steel mill could resume operations. With this
      perspective in mind, the metal industry has a long-standing opposition to the
      release of radioactive materials of any kind to commerce for fear of
      contamination and the potential consequences.

PMID- 17033461
TI  - A radioactive metal processing industry perspective source.
AB  - The current U.S. economic environment for the disposition of radioactive waste,
      including very-low-activity metals, is currently experiencing relatively low
      radioactive disposal costs and readily available disposal space. Despite the
      recent market increase in demand for recycled scrap metal commodities, there is
      still little change in the behavior of the nuclear industry (including
      radioactive waste processors and radioactive scrap metal recyclers) to pursue the
      recycling of potentially contaminated scrap metal. The relatively low cost of
      traditional radioactive waste disposal combined with the perceived risks
      associated with recycling of previously contaminated metals means that most U.S.
      radioactive facility managers and stakeholders will elect not to recycle. Current
      technology exists and precedence has been set for prescreening (by means of bulk
      radioactive assay techniques) scrap metal that is not contaminated and diverting
      it to industrial landfills for disposal. Other processes also allow some
      radiologically contaminated metals to be melted and recast into products with
      low, but acceptable, activity levels for restricted use in the nuclear industry.
      A new concept is being considered that would create a centralized licensed
      facility for the process and disposition of "very-low-activity" metals for
      "directed first use." The advantages to this type of approach would include a
      standardized method for licensing the clearance process.

PMID- 17033462
TI  - Low-activity radioactive materials management at the U.S. Department of Energy.
AB  - The U.S. Department of Energy (U.S. DOE) is making significant progress with the
      cleanup of its legacy radioactively-contaminated facilities and sites left from
      research and development and production of nuclear materials and weapons. Sites
      like Rocky Flats, Battelle Columbus Laboratories, Fernald, Mound, Brookhaven
      National Laboratory, Hanford, and Oak Ridge are faced daily with decisions
      related to disposition of waste and radioactive material. One key to this success
      is the disposition of waste arising from cleanup. Most of the generated waste
      volume has very low levels of radioactive contamination. The waste includes
      contaminated soil, debris from demolition, or scrap metal and equipment. The cost
      of disposing of large volumes of waste can be prohibitive, so there is incentive
      to find innovative ways to disposition wastes. This paper describes the current
      status of policy development in this area, such as development of a draft
      programmatic environmental impact statement and monitoring of related rulemaking
      at the U.S. Nuclear Regulatory Commission. The paper also provides an overview of
      draft U.S. DOE guidance on control and release of property with residual
      radioactive material, and site-specific applications of DOE guidance.

PMID- 17033463
TI  - Political life and half-life: the future formulation of nuclear waste public
      policy in the United States.
AB  - The United States continues to need forward-thinking and revised public policy to
      assure safe nuclear waste disposal. Both the high- and low-level disposal plans
      enacted by Congress in the 1980's have been frustrated by practical and political
      interventions. In the interim, ad hoc solutions and temporary fixes have emerged
      as de facto policy. Future statutory, regulatory, and administrative guidance
      will likely be less bold, more narrowly focused, and adopted at lower levels of
      government, more informally, in contrast to the top-down, statutory policies of
      the 1980's.

PMID- 17033464
TI  - An analysis of public-interest group positions on radiation protection.
AB  - The history of radiation risk management is replete with contentious public
      debate between public interest groups and the technical community of radiation
      protection professionals. To promote a deeper understanding of this phenomenon,
      this paper describes the rationales and values underlying public-interest group
      positions in one radiation risk domain (low-level waste) and contrasts them with
      those of the technical community. Public interest group objections to recycling
      of radioactivity-contaminated materials and to discarding of other low-level
      wastes are made on fairness, risk assessment, and energy-policy grounds. Concerns
      about procedural fairness stem from the continuing use of top-down expert-driven,
      rather than deliberative, systems for low-level waste policy-making. Concerns
      about distributional fairness arise because the benefits and risks of alterative
      low-level waste policies accrue to different stakeholders. Risk assessment is
      faulted for failure to acknowledge hidden subjective assumptions (e.g., on
      screening vigilance in materials recycling, on integrity of disposal facilities
      in the far future). Skepticism of technological risk management arises from a
      history peppered with unexpected untoward events that lay outside the design
      bases of protection systems. Finally, public interest groups view low-level waste
      issues as part of a larger debate on wise and legitimate energy policy, and are
      reluctant to support measures that provide relief to a nuclear industry that, in
      their view, established itself outside the democratic process.

PMID- 17033465
TI  - Policy development from the industry perspective.
AB  - The responsibility and burden for implementation of any option for the
      disposition of low-activity radioactive waste will primarily reside with the
      industries that generate the waste and those that provide the necessary waste
      management and disposal services. Unfortunately, there is no general consensus
      among these industries on the multiple policy issues that are critical to the
      application of an effective management and disposal program. This paper discusses
      the various policy issues that affect these industries and the problems that will
      likely occur during the course of their activities. These policy issues include
      public and political concern, opposition, and reaction; multiple and sometimes
      conflicting government agency jurisdiction, regulation, and policy; issues
      relating to the transition to a new comprehensive system; conflicts between the
      interests of the various industry groups; and operational, radiation safety, and
      regulatory implementation issues. For these reasons, the acceptable options may
      be limited. Case studies of various waste streams are included to show the
      specific impact and problems that these issues can create.

PMID- 17033466
TI  - Improving radioactive waste management: an overview of the Environmental
      Protection Agency's low-activity waste effort.
AB  - Radioactive waste disposal in the United States is marked by a fragmented
      regulatory system, with requirements that often focus on the origin or statutory
      definition of the waste, rather than the hazard of the material in question. It
      may be possible to enhance public protection by moving toward a system that
      provides disposal options appropriate for the hazard presented by the waste in
      question. This paper summarizes aspects of an approach focusing on the potential
      use, with appropriate conditions, of Resource Conservation and Recovery Act
      Subtitle-C hazardous waste landfills for disposal of "low-activity" wastes and
      public comments on the suggested approach.

PMID- 17033467
TI  - Current status of U.S. Nuclear Regulatory Commission regulatory efforts
      controlling the disposition of solid materials.
AB  - Current efforts of the U.S. Nuclear Regulatory Commission (U.S. NRC) to develop
      rules for the disposition of low-activity solid materials and the outcome of U.S.
      NRC rulemaking activities in this area since the late 1990's are described.
      International efforts on the disposition of low-activity solid materials and
      future plans of the U.S. NRC on this subject are also described.

PMID- 17033468
TI  - U.S. Department of Energy policies, directives, and guidance for radiological
      control and release of property.
AB  - U.S. Department of Energy (U.S. DOE) regulates its operations with a system of
      rules, directives, and guidance under the Atomic Energy Act. U.S. DOE's policy is
      to conduct its radiological operations in a manner that ensures the health and
      safety of its employees, contractors, and the public. U.S. DOE uses an annual
      dose limit of 100 mrem (1 mSv) with an "as low as reasonably achievable" (ALARA)
      process to achieve radiological protection. The primary directive for radiation
      protection of the public and the environment is DOE Order 5400.5. It contains
      requirements for the protection of the public and the environment from routine
      operations, including controlling and releasing property. Since the publication
      of Order 5400.5 in 1990, U.S. DOE has issued guidance for meeting requirements
      under it; Guide G 441.1-xx consolidates this guidance. DOE applies a dose
      constraint of 25 mrem y (0.25 mSy y(-1)), plus ALARA, for the release of real
      property, and 1 mrem y(-1), plus ALARA, for release of personal property. Models
      and guidance to develop the needed documentation for release of property are
      easily available and user-friendly. While achieving protection of human health
      and the environment, U.S. DOE's dose-based release process has resulted in
      significant cost savings. U.S. DOE has recently adopted a management systems
      approach for general environmental and public protection programs. The
      integration of the radiation protection program into this new approach is a high
      priority.

PMID- 17033469
TI  - Role of state regulatory agencies in the disposition of low-activity radioactive
      materials.
AB  - Since the opening of the first disposal site for commercially generated low-level
      radioactive waste at Beatty, Nevada, in September 1962, the states have been
      explicitly involved in the process. The states have been involved as landowners,
      regulators, environmental monitors, and sometimes promoters of the sites and/or
      the businesses operating the sites.

PMID- 17033470
TI  - Rapporteur's summary of presentations at the 2005 NCRP Annual Meeting.

PMID- 17033476
TI  - Critical care issues in liver transplantation.

PMID- 17033477
TI  - Coagulation and liver transplantation.

PMID- 17033478
TI  - Perioperative concerns in acute liver failure.

PMID- 17033479
TI  - 6/2/06 Perioperative assessment of the cardiovascular system in ESLD and
      transplantation.

PMID- 17033480
TI  - Perioperative management of the recipient of the extended criteria cadaveric
      donor liver (ECDL): a metabolic approach.

PMID- 17033481
TI  - An international look at liver transplantation and anesthesia care.

PMID- 17033482
TI  - Status and perspectives of liver transplantation in Argentina.

PMID- 17033483
TI  - Perioperative care of liver transplant patients in Brazil.

PMID- 17033484
TI  - An experience from China of perioperative care in 1510 liver transplant
      recipients.

PMID- 17033485
TI  - Perioperative management in adult and pediatric living related liver
      transplantation: an Egyptian experience.

PMID- 17033486
TI  - Liver transplantation in India.

PMID- 17033487
TI  - Liver transplantation in Poland: past, present, and future.

PMID- 17033488
TI  - Living donor liver transplantation: perioperative experience from Saudi Arabia.

PMID- 17033493
TI  - Methemoglobinemia: a novel way to noninvasively measure it by pulse oximetry.

PMID- 17033494
TI  - Lung cancer mortality in the German chromate industry, 1958 to 1998.

PMID- 17033496
TI  - The beryllium occupational exposure limit: historical origin and current
      inadequacy.

PMID- 17033498
TI  - Arsenic exposure and diabetes mellitus risk.

PMID- 17033500
TI  - Depression and pesticide exposures in female spouses of licensed pesticide
      applicators in the agricultural health study cohort.
AB  - OBJECTIVE: This nested case-control study evaluated the association between
      depression and pesticide exposure among women. METHODS: The study population
      included 29,074 female spouses of private pesticide applicators enrolled in the
      Agricultural Health Study between 1993 and 1997. Cases were women who had
      physician-diagnosed depression requiring medication. Lifetime pesticide use was
      categorized as never mixed/applied pesticides, low exposure (up to 225 days),
      high exposure (>225 days), and a history of diagnosed pesticide poisoning.
      RESULTS: After adjustment for state, age, race, off-farm work, alcohol, cigarette
      smoking, physician visits, and solvent exposure, depression was significantly
      associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95%
      confidence interval [CI] = 1.72-6.19) but not low (OR = 1.09; CI = 0.91-1.31) or
      high (OR = 1.09; 95% CI = 0.91-1.31) cumulative pesticide exposure. CONCLUSION:
      Pesticide poisoning may contribute to risk of depression.

PMID- 17033501
TI  - A projection of the impact of lipid-lowering therapy on high-risk employee
      disability and medical costs.
AB  - OBJECTIVE: The objective of this study was to examine the impact of introducing
      rosuvastatin calcium on direct and indirect costs among patients at high risk for
      coronary heart disease. METHODS: An economic simulation model was developed to
      project the number of cardiovascular events and associated direct and indirect
      costs under varying treatment scenarios. RESULTS: In an average-sized commercial
      health plan with 210,000 covered lives and 9,336 high-risk patients, an uptake of
      rosuvastatin by 11% of high-risk patients would result in eight fewer
      cardiovascular events, a net savings of 0.85 million dollars in direct medical
      costs and a net savings of 36,404 dollars in productivity loss over a period of 5
      years. The overall reduction in total costs is equivalent to 1735 dollars per
      rosuvastatin-treated patient. CONCLUSIONS: At current statin prices, the use of
      rosuvastatin could lead to fewer cardiovascular events and lower direct and
      indirect costs.

PMID- 17033502
TI  - Contribution of burnout to the association between job strain and depression: the
      health 2000 study.
AB  - OBJECTIVE: The objective of this study was to investigate the contribution of
      burnout to the association between job strain and depression. METHODS: A
      representative sample of 3270 Finnish employees aged 30 to 64 years responded to
      the Maslach Burnout Inventory-General Survey and the Beck Depression Inventory
      and participated in the Composite International Diagnostic Interview. RESULTS:
      High strain compared with low strain was associated with 7.4 (95% confidence
      interval [CI] = 5.6-9.7) times higher odds of burnout, 3.8 (95% CI = 2.8-5.1)
      times higher odds of depressive symptoms, and 1.7 (95% CI = 1.1-2.6) times higher
      odds of depressive disorders. The risk for depressive symptoms and for depressive
      disorders of high strain was reduced by 69% or more after adjusting for burnout.
      CONCLUSION: Burnout is strongly related to job strain and may in part mediate the
      association between job strain and depression.

PMID- 17033503
TI  - Employment as a welder and Parkinson disease among heavy equipment manufacturing
      workers.
AB  - OBJECTIVE: We investigated whether employment as a welder with potential exposure
      to manganese and other substances is associated with Parkinson disease (PD),
      parkinsonism or related neurological disorders, or accelerates the age of onset
      of PD. METHODS: We selected cases and controls from 12,595 persons ever employed
      at three Caterpillar Inc. (CAT) plants between 1976 and 2004 with potential to
      make a medical insurance claim between 1998 and 2004. Cases had filed a claim for
      1) PD, 2) "secondary parkinsonism", 3) "other degenerative diseases of the basal
      ganglia" or 4) "essential and other specific forms of tremor". Cases were grouped
      by claims: Group 1-claims 1 and 2 and Group 2-claims 1 to 4, and as study period
      incident (SPI) or prevalent. Each case was matched to two series of 10 controls
      each on date of case's first claim, year of birth, race and sex. Series I was
      also matched on plant. RESULTS: Odds ratios (OR) and 95% confidence intervals
      (CI) for the variable, "ever welder in any CAT plant" were: Group 1-SPI Cases:
      Series I (OR = .76, CI = .26-2.19), Series II (OR = .81, CI = .29-2.25); Group 1-
      Prevalent Cases: Series I (OR = .82, CI = .36-1.86), Series II (OR = .97, CI =
      .42-2.23); Group 2- SPI Cases: Series I (OR = 1.03, CI = .57-1.87), Series II (OR
      = 1.21, CI = .67-2.20) Group 2-Prevalent Cases: Series I (OR = 1.02, CI = .62
      1.71), Series II (OR = .86, CI = .51-1.43). Our finding of no statistically
      significant associations for welding employment was maintained following
      adjustment for potential confounding and evaluation of possible effect
      modification. Employment as a welder did not accelerate the age of onset of PD.
      CONCLUSIONS: Our study supported the conclusion that employment as a welder is
      not associated with Parkinson disease, parkinsonism or a related neurological
      disorder.

PMID- 17033504
TI  - Firefighter heart presumption retirements in Massachusetts 1997-2004.
AB  - OBJECTIVE: "Heart Presumption" legislation is common throughout North America. We
      sought to study Massachusetts firefighters retiring with heart disability awards.
      METHODS: The authors conducted a retrospective review of Massachusetts
      firefighters: 362 receiving Heart Presumption pensions (1997-2004) and a
      comparison group of 310 professionally active firefighters. RESULTS: Of
      retirements, 77% were due to coronary heart disease and 23% for other
      cardiovascular conditions. Only 42% of the retirements were related to discrete
      on-duty events. Fire suppression (odds ratio = 51, 95% confidence interval = 12
      223) and alarm response (odds ratio = 6.4, 95% confidence interval = 2.5-17) were
      associated with markedly higher risks of duty-related heart retirement events
      than nonemergency activities. Cardiovascular risk factor prevalence was high
      among all retiree subgroups and significantly greater than among control
      firefighters in almost all cases. CONCLUSIONS: Our study supports calls for
      improved cardiovascular prevention and risk reduction strategies among
      firefighters.

PMID- 17033505
TI  - Use of medical insurance claims data for occupational health research.
AB  - OBJECTIVE: The objective of this study was to demonstrate that health claims
      data, widely available due to the unique nature of the U.S. healthcare system,
      can be linked to other relevant databases such as personnel files and exposure
      data maintained by large employers. These data offer great potential for
      occupational health research. METHODS: In this article, we describe the process
      for linking claims data to industrial hygiene exposure data and personnel files
      of a single large employer to conduct epidemiologic research. RESULTS: Our
      results demonstrate the ability to replicate previously published findings using
      commonly maintained data sets and illustrate methodological issues that may arise
      as newer hypotheses are tested in this way. CONCLUSIONS: Health claims files
      offer potential for epidemiologic research in the United States, although the
      full extent and guidelines for successful application await further clarification
      through empiric research.

PMID- 17033506
TI  - Risk factors for asthma among cosmetology professionals in Colorado.
AB  - PROBLEM: After receiving several reports of occupational asthma among cosmetology
      professionals, we studied the prevalence, work-attributable risk, and tasks
      associated with asthma in this industry. METHODS: We selected a stratified random
      sample of cosmeticians, manicurists, barbers, and cosmetologists holding licenses
      in Colorado for a mail survey instrument. RESULTS: The prevalence of physician
      diagnosed asthma among the 1883 respondents (68% response rate) was 9.3%; of
      these, 67 (38%) developed asthma after entering the cosmetology profession.
      Multivariate analyses showed that hairstyling, application of artificial nails,
      and shaving and honing were significantly associated with asthma arising in the
      course of employment (P < 0.005) with relative risks of 2.6-2.9. CONCLUSIONS: The
      increased risk of asthma with onset during employment among cosmetologists is
      probably attributable to their exposure to sensitizers and irritants in tasks
      demonstrated to be associated with asthma.

PMID- 17033507
TI  - Mortality among Rocketdyne workers who tested rocket engines, 1948-1999.
AB  - OBJECTIVE: The objective of this study was to evaluate potential health risks
      associated with testing rocket engines. METHODS: A retrospective cohort mortality
      study was conducted of 8372 Rocketdyne workers employed 1948 to 1999 at the Santa
      Susana Field Laboratory (SSFL). Standardized mortality ratios (SMRs) and 95%
      confidence intervals (CIs) were calculated for all workers, including those
      employed at specific test areas where particular fuels, solvents, and chemicals
      were used. Dose-response trends were evaluated using Cox proportional hazards
      models. RESULTS: SMRs for all cancers were close to population expectations among
      SSFL workers overall (SMR = 0.89; CI = 0.82-0.96) and test stand mechanics in
      particular (n = 1651; SMR = 1.00; CI = 0.86-1.16), including those likely exposed
      to hydrazines (n = 315; SMR = 1.09; CI = 0.75-1.52) or trichloroethylene (TCE) (n
      = 1111; SMR = 1.00; CI = 0.83-1.19). Nonsignificant associations were seen
      between kidney cancer and TCE, lung cancer and hydrazines, and stomach cancer and
      years worked as a test stand mechanic. No trends over exposure categories were
      statistically significant. CONCLUSION: Work at the SSFL rocket engine test
      facility or as a test stand mechanic was not associated with a significant
      increase in cancer mortality overall or for any specific cancer.

PMID- 17033508
TI  - Impairment in workers with isocyanate-induced occupational asthma and removed
      from exposure in the province of Quebec between 1985 and 2002.
AB  - OBJECTIVE: The objective of this project was to assess both the outcome for
      patients diagnosed with proven isocyanate-induced occupational asthma (IIOA) by
      specific inhalation challenge (SIC) and the functional impairment, 2 years after
      cessation of exposure to isocyanates, using the compensation insurance scale
      proposed in the province of Quebec. METHODS: We used a retrospective cohort of
      233 patients diagnosed in the province of Quebec between 1985 and 2002 and
      randomly chose 105 of those patients. We kept 89 subjects with complete data at
      T0 (the time of diagnosis) and 79 were reevaluated at T2, approximately 2 years
      after their removal from exposure, for final impairment-disability assessment. At
      each evaluation (T0 and T2), a clinical examination and lung function tests,
      including spirometry and methacholine challenge, were performed. RESULTS: At T2,
      79 of 89 patients were reassessed (89%). The remaining patients were lost to
      follow up (8) or too unstable to be reassessed for final impairment-disability
      settlement (2). No statistical difference was observed for spirometry data and
      antiasthmatic medication use between T0 and T2 (P = 0.11). At T2, 73% of patients
      were still using short-acting beta2 agonists and 39% inhaled glucocorticoids. A
      forced expiratory volume in 1 second variation of +/-10% from T0 to T2 occurred
      in 31 subjects (40%). Forced expiratory volume in 1 second worsened in 14 (18%),
      remained significantly unchanged in 51 (64%), and improved in 14 (18%).
      Nonspecific bronchial hyperresponsiveness (BHR) improved in significantly in 19
      (24%); the others remained unchanged. Both were not associated with smoking
      status (P > 0.05). Nonspecific BHR was normalized in nine of 79 (11%) patients.
      Clinical remission occurred in only four (5%) subjects. The mean impairment
      disability score was 21% +/- 13% at 2 years according to the scale used by the
      Workers' Compensation Board. CONCLUSIONS: These results show the generally poor
      medical outcome of IIOA and suggest the importance of early detection and
      withdrawal of the workers from exposure to isocyanates. They also emphasize the
      need for medical surveillance program and adequate treatment of patients with
      IIOA.

PMID- 17033509
TI  - Effect of smoking status on productivity loss.
AB  - OBJECTIVE: The objective of this study was to describe health-related
      productivity losses in nonsmokers, former smokers, and current smokers using a
      large, cross-sectional database of U.S. employees. METHODS: Volunteers completed
      the Wellness Inventory, an instrument measuring productivity losses related to 11
      health conditions affecting employee health. Results are aggregated, dollarized,
      and reported by smoking group. RESULTS: Current smokers missed more days of work
      and experienced more unproductive time at work compared with former smokers and
      nonsmokers. The average annual cost for lost productivity for nonsmokers was 2623
      dollars/year compared with 3246 dollars/year for former smokers and 4430
      dollars/year for current smokers. More than half the costs were due to
      unproductive time at work. CONCLUSION: Current smokers incurred the highest
      productivity losses, which translated into higher costs to employers for current
      smokers. Costs were lower for former smokers and nonsmokers.

PMID- 17033512
TI  - Hereditary colonic varices--image of the month.

PMID- 17033513
TI  - The match for US pediatric gastroenterology and nutrition fellowships.

PMID- 17033514
TI  - Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data
      and implications for future research.
AB  - Although population prevalence is very difficult to establish, nonalcoholic fatty
      liver disease (NAFLD) is probably the most common cause of liver disease in the
      preadolescent and adolescent age groups. There seems to be an increase in the
      prevalence of NAFLD, likely related to the dramatic rise in the incidence of
      obesity during the past 3 decades. Despite an increase in public awareness,
      overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed
      by health care providers. Accurate diagnosis and staging of nonalcoholic
      steatohepatitis (NASH) requires liver biopsy. The development of noninvasive
      surrogate markers and the advancements in imaging technology will aid in the
      screening of large populations at risk for NAFLD. Two distinct histological
      patterns of NASH have been identified in the pediatric population, and discrete
      clinical and demographic features are observed in children with these 2 patterns.
      The propensity for NASH to develop in obese, insulin-resistant pubertal boys of
      Hispanic ethnicity or a non-Hispanic white race may provide clues to the
      pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet
      to be defined, but most biopsies in this age group demonstrate some degree of
      fibrosis. In addition, cirrhosis can be observed in children as young as 10
      years. While the optimal treatment of pediatric NAFLD has yet to be determined,
      lifestyle modification through diet and exercise should be attempted in children
      diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is
      underway as part of the NASH clinical research network.

PMID- 17033515
TI  - Rapid growth in infancy: balancing the interests of the child.
AB  - Low birth weight is associated with a number of immediate adverse consequences,
      and it has been assumed that "catch-up" growth is a "good thing" because "better"
      nutritional status is associated with greater childhood health and survival. The
      same thinking applies to infants who suffer malnutrition and growth faltering
      during weaning. Recent studies suggest that the rapid postnatal growth of babies
      is associated with an enhanced risk for obesity, diabetes, hypertension,
      cardiovascular disease and osteopenia in later life. If this is true, it has
      implications for our recommendations for infant feeding. Insights from
      evolutionary biology, life cycle theory, animal husbandry, epidemiology and
      comparative zoology suggest that the energetic feeding of underweight infants
      should be considered in the context of the whole life cycle and balance the
      interests of the child with its likely fortunes in adulthood. Before we revise
      our current recommendations, we must consider the meaning of catch-up growth,
      what it involves in terms of tissues gained (fat, muscle and bone) and to what
      degree association represents causation. In the meantime, it will be prudent to
      balance the short- and long-term interests of the child by endeavoring to (1)
      optimize maternal nutrition and health, to avoid low birth weight, (2) breast
      feed ideally, (3) consider birth weight, gestation and future "nutritional
      environment" when making decisions about infant feeding, (4) use appropriate
      growth charts, (5) avoid excessive postnatal weight gain, (6) think about the
      whole life span and (7) extrapolate from animal studies cautiously.

PMID- 17033516
TI  - Interventions to improve cardiovascular risk factors in obese children.

PMID- 17033517
TI  - Appropriate management of severe malnutrition greatly contributes to the
      reduction of child mortality rate.

PMID- 17033518
TI  - Cytokine expression in rat colon during postnatal development: regulation by
      glucocorticoids.
AB  - OBJECTIVES: Cytokine expression and regulation by glucocorticoids and retinoic
      acid were investigated in the colon during postnatal development. MATERIALS AND
      METHODS: Gene expression of the transforming growth factors (TGFs) TGF-beta1, TGF
      beta2 and TGF-alpha and the proinflammatory cytokines tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta) was evaluated by reverse
      transcription-polymerase chain reaction (RT-PCR) in rat colon mucosa during
      weaning and in adult rats. Protein expression and distribution of TGF-betas was
      analysed in the colon from 14- and 60-day-old animals. The effect of
      hydrocortisone administration on mucosal cytokine transcripts (RT-PCR) and of
      dexamethasone on the expression of cytokines by the epithelial cell line IEC-18
      and 2 subepithelial myofibroblasts (MIC 307-1 and 316) was examined. RESULTS: TGF
      beta1 and TGF-beta2 messenger RNAs and proteins decreased in the entire colon
      from weaning to adult stages, whereas the amount of TGF-alpha messenger RNA
      increased in the proximal colon and decreased in the distal part of the colon in
      adult rats in comparison with weanlings. However, proinflammatory cytokines
      showed no postnatal changes in the proximal colon but decreased in the distal
      part in comparison with weaning rats. Hydrocortisone treatment did not affect
      growth factor expression but decreased proinflammatory cytokines. Likewise,
      dexamethasone decreased TNF-alpha and IL-1beta gene expression but did not affect
      TGF-betas in either epithelial or myofibroblast cells. CONCLUSIONS: During
      postnatal maturation, the expression of growth factors and proinflammatory
      cytokines decreased in the distal colon, whereas in the proximal colon, a
      differential maturation occurs with no changes in proinflammatory cytokines, an
      increase in TGF-alpha and a decrease in TGF-beta. Glucocorticoids may control the
      developmental profile of proinflammatory cytokines.

PMID- 17033519
TI  - Stimulation of immunity without alteration of oral tolerance in mice fed with
      heat-treated fermented infant formula.
AB  - OBJECTIVES: Little information is available on the properties of fermented milk
      formula intended to healthy infants. This study analyzes the effect of long-term
      ingestion of a heat-treated, fermented milk formula on the development of oral
      tolerance or systemic immune response to soluble antigens in mice. MATERIALS AND
      METHODS: The C3H/HeN mice, fed with a heat-treated fermented (Bifidobacterium
      breve C50 and Streptococcus thermophilus 065) infant formula (htFF) or a matched
      control diet (control), were immunized with ovalbumin (OVA) with or without
      gavage of 20 mg OVA to induce tolerance or immunity, respectively. Systemic and
      local anti-OVA immune responses and intestinal barrier function were measured
      after 5 to 6 weeks. RESULTS: Oral tolerance to OVA developed similarly in htFF-
      and control-fed mice, attested to by the downregulation of OVA-specific
      immunoglobulin (Ig) G and IgE after oral OVA administration. In contrast,
      immunization with OVA led to significantly higher titers in htFF-fed mice than in
      control-fed mice (log2 IgG titers, 16.45 +/- 1.24 and 15.46 +/- 0.79,
      respectively; P = 0.012). Jejunal interferon gamma, interleukin 12p40 and
      interleukin 10 expressions were significantly higher in tolerized mice fed with
      htFF compared with those fed with the control diet. Mucosal to serosal intact
      horseradish peroxidase fluxes were lower in htFF-fed mice than in control-fed
      mice (39 +/- 8 and 118 +/- 38 ng/h x cm2, respectively; P < 0.0001), indicating
      that the htFF diet reinforces intestinal barrier capacity to macromolecules.
      CONCLUSIONS: In mice, htFF strengthens intestinal barrier and enhances systemic
      immune responses to antigens without interfering with the development of oral
      tolerance, suggesting a potential beneficial effect in host defence and
      vaccination.

PMID- 17033520
TI  - In vivo and in vitro effects of tea extracts on enterotoxigenic Escherichia coli
      induced intestinal fluid loss in animal models.
AB  - OBJECTIVES: Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of
      dehydrating diarrhoea in infants and early-weaned piglets living under
      subhygienic conditions. We studied the effect of different tea types and
      subfractions on the intestinal fluid and electrolyte losses involved in ETEC
      diarrhoea. MATERIALS AND METHODS: Jejunal segments of anaesthetised piglets were
      infected with ETEC or ETEC heat-labile toxin (LT) and subsequently perfused for 8
      hours with control or tea solutions containing green or black tea extract (BTE)
      or 3 different BTE subfractions containing small-size, large-size or no
      phenolics. Changes in intestinal fluid and electrolyte net absorption were
      measured. To assess the antisecretory effects of tea, BTE was incubated before or
      after administration of the secretagogue forskolin in rat jejunal tissue placed
      in Ussing chambers and Cl- secretion measured as changes in short-circuit current
      (I(SC)). RESULTS: Enterotoxigenic E. coli infection of piglet jejunal segments
      significantly reduced net absorption of fluid, Na+ and Cl- and increased net
      secretion of K+ compared with controls. Perfusion of the ETEC-infected segments
      with both 3 g/L green tea extract and BTE significantly inhibited these
      disturbances in fluid and electrolyte balance. The BTE subfraction rich in
      polymeric phenolics but not the other subfractions improved the fluid and
      electrolyte balance. Addition of forskolin to rat jejunal tissue induced a
      significant increase in I(SC). Pretreating but not posttreating the jejunal
      tissue with BTE inhibited the forskolin-induced increase in I(SC). CONCLUSIONS:
      Tea may inhibit net fluid and electrolyte losses involved in secretory diarrhoea
      from ETEC.

PMID- 17033521
TI  - Intestinal cytokine mRNA expression in delayed-type cow's milk allergy.
AB  - OBJECTIVES: The aim of the study was to investigate the characteristics of
      intestinal immune activation (ie, a chemokine receptor and cytokine expression
      profile) in delayed-type cow's milk allergy (CMA) appearing in the form of
      gastrointestinal symptoms. PATIENTS AND METHODS: In all biopsy samples taken from
      the duodenum and/or the terminal ileum, 30 were studied for the expression of
      interferon-gamma, transforming growth factor-beta, chemokine receptor (CCR)-4,
      CCR-5, IL-2, IL-6, IL-10, IL-12p35, IL-12p40 and IL-18 specific mRNA by real-time
      quantitative reverse transcriptase-polymerase chain reaction in 26 children ages
      3 to 15 years: 10 with untreated delayed-type CMA, 6 with celiac disease (CD) and
      10 controls. RESULTS: The children with delayed-type CMA showed lower IL-2 and IL
      18 mRNA expression in the duodenum (both P = 0.055) and higher CCR-4 and IL-6
      mRNA expression in the terminal ileum (P = 0.055, P = 0.016) compared with the
      controls. The children with CD exhibited slightly higher expression of interferon
      gamma and CCR-4 mRNA (P = 0.054, P = 0.053) and lower expression of IL-18 mRNA (P
      = 0.004) in the duodenal samples compared with the controls. The mRNA expression
      levels of regulatory cytokines, transforming growth factor-beta and IL-10
      remained similar in all 3 groups. CONCLUSIONS: The children with delayed-type
      gastrointestinal CMA showed a unique pattern of local intestinal hypersensitivity
      with Th2 response-related characteristics, a profile differing clearly from the
      children with CD.

PMID- 17033522
TI  - A prospective community-based study of gastroenterological symptoms in school-age
      children.
AB  - INTRODUCTION: Current knowledge on the prevalence of common gastrointestinal (GI)
      problems is based on office-based samples or retrospective questionnaires,
      leading to possible bias and inaccurate estimates. AIMS: To examine the
      prevalence of GI symptoms in school-age children. IMPORTANCE: This is the first
      American prospective community study intended to assess the prevalence of common
      GI symptoms in children. PATIENTS AND METHODS: All fourth- and fifth-grade
      students from a middle-size urban school were invited to participate in a
      prospective cohort pilot study by completing confidential weekly surveys. The
      survey included a set of 8 age-appropriate, validated questions assessing the
      presence and severity of abdominal pain, constipation, diarrhea, nausea,
      vomiting, chest pain, headaches and limb pain. RESULTS: A total of 48 children
      (32 boys and 16 girls) participated in the study. Data were obtained for 16 weeks
      on 690 (90.5%) of 768 possible children per week. Children reported at least 1
      symptom in 544 (70%) children per week. Headaches were the most common complaint
      (55% [range, 40%-72%] children per week). Sixty percent of children (range, 46%
      89%) reported at least 1 GI symptom weekly. The overall prevalence of GI symptoms
      was the following: abdominal pain 46% (range, 28%-72%), nausea 28% (range, 17%
      59%), constipation 18% (range, 7%-39%), diarrhea 17% (range, 11%-24%) and
      vomiting 5% (range, 0%-13%). None of the children missed school because of
      persistent GI symptoms during the study. DISCUSSION: The investigation
      demonstrates the feasibility of prospective school studies in children. The high
      prevalence of GI symptoms not interfering with school attendance in children
      underscores the benign nature of such symptoms in most children. CONCLUSION:
      Gastrointestinal symptoms are common somatic complaints among school-age
      children.

PMID- 17033523
TI  - Patient-reported symptoms after pediatric outpatient colonoscopy or flexible
      sigmoidoscopy under general anesthesia.
AB  - OBJECTIVES: Endoscopic examination of the colon is indicated in children with
      diarrhea, hematochezia and suspected inflammatory bowel disease. The aim of this
      study was to determine the rate of patient-reported symptoms after colonoscopy
      and flexible sigmoidoscopy under general anesthesia in children. PATIENTS AND
      METHODS: This prospective study included patients 18 years of age and younger who
      underwent colonoscopy or flexible sigmoidoscopy during a 1-year period. At least
      30 days after the endoscopy, an interview was conducted regarding symptoms after
      colonoscopy or flexible sigmoidoscopy. RESULTS: Eighty-eight children were
      eligible, and 68 (77%) were available for follow-up. Ten (15%) reported symptoms
      after their endoscopy. The most common symptoms reported were diarrhea, excessive
      gas and sore throat. The frequency of reported symptoms was similar between
      colonoscopy and flexible sigmoidoscopy. The frequency of symptoms was not
      affected by intubation of terminal ileum, polypectomy or the number of prior
      colonoscopies or flexible sigmoidoscopies. CONCLUSIONS: Outpatient colonoscopy
      and flexible sigmoidoscopy under general anesthesia are well tolerated by
      children. A minority of children reports mild symptoms that spontaneously
      resolve.

PMID- 17033524
TI  - Liver transplantation and chemotherapy in children with unresectable primary
      hepatic malignancies: development of a management algorithm.
AB  - OBJECTIVES: Total surgical excision and adjunctive chemotherapy are cornerstones
      of treatment of primary hepatic malignancies in children. Recent studies suggest
      that transplantation is a viable option for unresectable tumors, but there are
      questions concerning decision making regarding resectability and timing of
      transplantation in relation to chemotherapy. We developed a management algorithm
      based on our experience, with reference to recently published multicenter
      transplantation outcomes. RESULTS: Nine patients underwent transplantation
      (median age, 38 months; 7 hepatoblastoma, 2 undifferentiated mesenchymal
      sarcoma). All were assessed unresectable at presentation. After chemotherapy, 7
      remained unresectable and had primary transplantation, 1 developed chemotherapy
      related liver failure, necessitating emergent transplantation, and 1 was deemed
      resectable, requiring rescue transplantation after local recurrence. Using a
      timely living/cadaver donor graft acquisition strategy relative to chemotherapy,
      median waiting time from listing was 8 days. After transplantation, 3 of 9 had
      chemotherapy, with side effects dictating discontinuation in 2; 6 of 9 had no
      chemotherapy, with 2 developing distant metastases, 1 of whom died 12 months
      posttransplantation. Median follow-up was 3.08 years. Overall survival was 89%.
      CONCLUSIONS: Primary transplantation can be highly successful in children with
      hepatic tumors. These outcomes compare favorably with multicenter studies, where
      waiting-list deaths are reported and survival after rescue transplantation is
      poor. We encourage timely transplantation in the setting of questionably
      resectable tumors or evidence of chemotherapy resistance. The necessity of
      posttransplantation chemotherapy is questioned. Consultation with a
      transplantation program before chemotherapy should avoid inappropriate attempts
      at resection and allow appropriate planning of transplantation in relation to
      chemotherapy.

PMID- 17033525
TI  - Long-term lamivudine therapy for chronic hepatitis B infection in children
      unresponsive to interferon.
AB  - OBJECTIVES: Prolonged lamivudine treatment in adults has been shown to improve
      hepatitis B e (HBe) seroconversion rates in patients with chronic hepatitis B.
      This prospective open study reports the results of prolonged lamivudine treatment
      in a group of children with chronic hepatitis B. PATIENTS AND METHODS: Twenty-two
      children and adolescents age 13.2 years (range, 9.5-18 years), who have been
      treated with lamivudine for 1 year, continued treatment with lamivudine (3
      mg/kg/day, up to 100 mg/d) as long as there was evidence of continued biochemical
      and virological benefit compared with baseline. We evaluated virological and
      biochemical responses, the occurrence of YMDD mutants and adverse effects during
      4 years of follow-up. RESULTS: After 4 years on lamivudine, only 4 patients (18%)
      underwent HBe seroconversion. In addition, in 3 patients (13%), the treatment was
      stopped when lamivudine's lack of efficacy became evident. During the 4-year
      study period, we recorded a continuing decline in the participants' number,
      mostly because of lack of compliance with treatment (9/22, 41%). Only 5 children
      were still receiving lamivudine and showing benefit after 4 years. In 2 children,
      treatment termination and YMDD mutant emergence were associated with hepatitis
      flare. Besides subclinical elevation of creatine phosphokinase, no other adverse
      events were recorded during the study period. CONCLUSIONS: Four years after
      starting lamivudine treatment, most children from this study were off lamivudine,
      mainly because of lack of compliance and poor HBe seroconversion. These findings
      suggest that continuing treatment with lamivudine for undefined periods is hard
      to implement and does not improve HBe seroconversion.

PMID- 17033526
TI  - Safety, efficacy and pharmacokinetics of peginterferon alpha2a (40 kd) in
      children with chronic hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection in children is a problem affecting
      thousands of children worldwide. Although standard interferon (INF) has better
      efficacy in pediatric patients than in adults, results in children with genotype
      1 are poor; response rates to combination treatment with standard INF and
      ribavirin are better but the treatment requires thrice-weekly injections. The
      improved antiviral efficacy of weekly pegylated interferons relative to standard
      interferons in adults with chronic HCV infection suggests that pegylated
      interferons may also improve antiviral efficacy in children. We therefore
      investigated the pharmacokinetics, efficacy and safety of peginterferon alpha2a
      (pegINF-alpha2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis
      C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's
      body surface area (BSA) according to the formula BSA (m2)/(1.73 m2) x 180 microg,
      and patients were administered once-weekly subcutaneous injections for 48 weeks.
      Viral load and pharmacokinetic parameters were determined from blood drawn
      throughout the study and during follow-up. At week 24, the mean trough
      concentration was about 20% below values obtained from adults treated with pegINF
      alpha2a, and the area under the curve from 0 to 168 hours was about 20% above
      adult values, suggesting that drug doses calculated from BSA achieved
      therapeutically adequate concentrations. Six of 14 patients (43%), all infected
      with genotype 1, achieved a sustained virological response. Adverse events were
      those commonly associated with INF-based treatment, and none was deemed serious.
      In conclusion, our findings provide a basis for larger studies evaluating the
      efficacy and safety of pegINF-alpha2a as monotherapy as well as in combination
      with ribavirin in pediatric patients with chronic hepatitis C.

PMID- 17033527
TI  - Changes of cardiovascular risk factors in obese children effects of inpatient and
      outpatient interventions.
AB  - OBJECTIVE: The aim of the study was to compare the benefits of 2 different
      therapeutic approaches on cardiovascular risk factors (CVRF) in obese children
      and adolescents. METHODS: We analyzed the changes of weight status (as standard
      deviation score-body mass index [SDS-BMI]), blood pressure, lipids, and insulin
      levels in obese children (age range, 10-14 years) during a 1-year outpatient
      intervention based on lifestyle changes (group A, n = 124) and during a 6-week
      inpatient intervention program with dietary restriction and exercise therapy
      (group B, n = 119). In addition, we studied these parameters in 65 obese children
      without intervention for 1 year (control group). RESULTS: Age, degree of
      overweight, sex, and CVRF did not differ significantly between the control group
      and the intervention groups at baseline. During the observation period, CVRF did
      not change in the control group, whereas SDS-BMI slightly increased (+0.1 SDS
      BMI). The SDS-BMI decreased significantly (P < 0.001) in group A (SDS-BMI, -0.40)
      and comparably in group B (SDS-BMI, -0.43). The decreases of total (P < 0.001)
      and low-density lipoprotein-cholesterol levels (P = 0.049) were significantly
      greater in group B, whereas triglyceride (P = 0.040) and insulin (P = 0.006)
      levels decreased significantly and were more pronounced in group A. High-density
      lipoprotein-cholesterol level increased significantly (P < 0.001) only in group
      A. Blood pressure decreased significantly (P < 0.01) and comparably in both
      intervention groups (A and B). CONCLUSIONS: In contrast to obese children without
      intervention, CVRF improved in obese children with intervention. The 6-week
      inpatient intervention led to a significant greater decrease of total and low
      density lipoprotein-cholesterol levels as compared with the 1-year outpatient
      intervention, although the outpatient intervention yielded a significantly
      greater improvement in insulin, triglycerides, and high-density lipoprotein
      cholesterol levels.

PMID- 17033528
TI  - Effect of a low-cost food on the recovery and death rate of malnourished
      children.
AB  - OBJECTIVES: Nutritional rehabilitation in Africa relies mainly on imported skim
      milk enriched with a sugar and salt mixture. We evaluated whether milk plus
      porridge made from local ingredients improves the outcome of childhood
      nutritional rehabilitation versus milk alone. PATIENTS AND METHODS: This study
      was conducted in a nutritional unit in Lacor (Northern Uganda). The porridge,
      made from cheap locally available ingredients (maize flour, dried fish or meat,
      peanut butter and oil) supplemented with proteins and fats, provides 1.1 energy
      units, 4.4 kJ/g. We randomly sampled the files of 100 cases discharged in
      October, November and December 2001 (preintervention), in 2002 (soon after
      intervention onset) and in 2003 (more than 1 year after intervention onset). We
      recorded the average hospital days and average oedema-free weight gain at
      discharge in the 3 groups. RESULTS: Average oedema-free weight gain increased
      from 21 g/d (95% confidence interval [CI], 12-29) in 2001 to 35 g/d (95% CI, 25
      45) in 2002 and reached 59 g/d (95% CI, 51-65) in 2003. Mortality decreased from
      22% to 7.8%, and nutritional failures (insufficient weight gain) decreased by
      greater than 50%. CONCLUSIONS: The low-cost porridge supplement (2640 euros/yr
      per 100 children) was effective in treating malnutrition. Widespread use of the
      porridge, which resulted in better outcomes than milk alone, could produce a
      savings in the medium- to long-term, thereby releasing resources for other uses.
      A high-energy porridge that is made from locally available ingredients and does
      not require imported foods seems to be appropriate for supplementary feeding
      after mother's milk in this setting.

PMID- 17033529
TI  - Effects of age and time on energy and macronutrient intake in German infants and
      young children: results of the DONALD study.
AB  - OBJECTIVES: To describe effects of age and time on the intake of energy and
      macronutrients in infants and young children. PATIENTS AND METHODS: The energy
      and macronutrient intake of 720 DONALD study participants between 1989 and 2003
      was evaluated by analysing 3027 three-day weighed dietary records (including test
      weighing of breast milk consumption) at 3, 6, 9, 12, 18, 24 and 36 months. Mixed
      models and logistic regression analyses were used to investigate the effects of
      age and time on intake. RESULTS: Age affected macronutrient patterns (percentage
      of energy intake, E%) more often in infants than in young children. The
      percentage of full and partial breast-fed infants increased between 1989 and
      2003. Almost no time trends were found for energy intake. Macronutrient patterns
      changed with time; for example, protein intake decreased throughout infancy
      (between -0.05 and -0.17 E%/y). An increase in fat intake (0.23 and 0.40 E%/y)
      was compensated by a decrease in carbohydrates (-0.18 and -0.29 E%/y) in young
      infants (3 and 6 months). Opposite trends in macronutrient patterns were observed
      in infants and young children. CONCLUSIONS: Increasing breast milk consumption
      over time was the most obvious factor influencing long-term trends in
      macronutrient patterns. In all of the age groups examined here, macronutrient
      patterns have come closer to the references over time.

PMID- 17033530
TI  - Growth and change in blood haemoglobin concentration among underweight Malawian
      infants receiving fortified spreads for 12 weeks: a preliminary trial.
AB  - OBJECTIVE: Fortified spreads (FSs) have proven effective in the rehabilitation of
      severely malnourished children. We examined acceptability, growth and change in
      blood haemoglobin (Hb) concentration among moderately underweight ambulatory
      infants given FS. METHODS: This was a randomised, controlled, parallel-group,
      investigator-blind clinical trial in rural Malawi. Six- to 17-month-old
      underweight infants (weight for age < -2), whose weight was greater than 5.5 kg
      and weight-for-height z score greater than -3 received for 12 weeks at home 1 of
      8 food supplementation schemes: nothing, 5, 25, 50, or 75 g/day milk-based FS or
      25, 50, or 75 g/day soy-based FS. Outcome measures included change in weight,
      length and blood Hb concentration. RESULTS: A total of 126 infants started and
      125 completed the intervention. All infants accepted the spread well, and no
      intolerance was recorded. Average weight and length gains were higher among
      infants receiving daily 25 to 75 g FS than among those receiving only 0 to 5 g
      FS. Mean Hb concentration remained unchanged among unsupplemented controls but
      increased by 10 to 17 g/L among infants receiving any FS. All average gains were
      largest among infants receiving 50 g of FS daily: mean difference (95% confidence
      interval) in the 12-week gain between infants in 50 g milk-based FS group and the
      unsupplemented group was 290 g (range, -130 to 700 g), 0.9 cm (range, -0.3 to 2.2
      cm), and 17 g/L (range, 0 to 34 g/L) for weight, length and blood Hb
      concentration, respectively. In soy- vs milk-based FS groups, average outcomes
      were comparable. CONCLUSIONS: Supplementation with 25 to 75 g/day of highly
      fortified spread is feasible and may promote growth and alleviate anaemia among
      moderately malnourished infants. Further trials should test this hypothesis.

PMID- 17033531
TI  - Vertebral fractures and increased sensitivity to corticosteroids in a child with
      ulcerative colitis: successful use of pamidronate.

PMID- 17033532
TI  - Acute hepatitis and liver failure associated with influenza A infection in
      children.

PMID- 17033533
TI  - Gastric pneumatosis intestinalis: an indicator of intestinal perforation in
      preterm infants with necrotizing enterocolitis?

PMID- 17033534
TI  - A child with Kabuki syndrome and primary sclerosing cholangitis successfully
      treated with ursodiol and cholestryamine.

PMID- 17033535
TI  - Therapy with gastric acidity inhibitors increases the risk of acute
      gastroenteritis and community-acquired pneumonia in children.

PMID- 17033536
TI  - Antiemetics for acute gastroenteritis: a never ending story.

PMID- 17033537
TI  - The adipokine visfatin is markedly elevated in obese children.
AB  - OBJECTIVE: The insulin-mimetic adipocytokine visfatin has been linked to
      adiposity and the metabolic syndrome. DESIGN: Cross-sectional study. SUBJECTS:
      Eighty-three nondiabetic obese children and 40 healthy controls. MEASUREMENTS: We
      analyzed plasma visfatin concentrations to assess whether this adipokine is
      associated with adiposity. RESULTS: Plasma visfatin concentrations were nearly 2
      fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2-6.6) than in controls
      (0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable
      between visfatin and other subject characteristics, hsCRP or the lipid profile.
      CONCLUSIONS: Visfatin may be involved in the development of metabolic
      derangements in obese children.

PMID- 17033538
TI  - Clinical efficacy of probiotics: review of the evidence with focus on children.
AB  - Probiotics are marketed in several countries and widely used by pediatric health
      care providers. Although probiotics can be helpful for specific disorders, they
      have been broadly prescribed for disorders without clear evidence to support
      their use. Furthermore, in certain specific conditions, probiotics cause clinical
      deterioration. This report is a review and evaluation of the evidence or lack
      thereof to support a beneficial effect of probiotic agents in a variety of
      pediatric conditions and to review the safety and potential adverse events that
      may be encountered when using probiotics. It is also important to emphasize that
      probiotics are highly heterogeneous with differences in composition, biological
      activity, and dose among the different probiotic preparations.

PMID- 17033539
TI  - The future of emergency care for America: in crisis, at peril and in need of
      resuscitation!

PMID- 17033540
TI  - Do early ionized calcium levels really matter in trauma patients?
AB  - BACKGROUND: Age, injury severity, and base deficit are commonly used prognostic
      indicators in trauma. This study investigates the relationship between ionized
      calcium (iCa) levels drawn on arrival to the emergency department, with injury
      severity, acidosis, hypotension, and mortality. METHODS: Adult trauma team
      activations requiring the highest level of response were identified
      retrospectively from January 2000 to December 2002. Patients were stratified into
      two groups: iCa < or = 1 and iCa > 1 mmol/L. The relationship between iCa and
      injury severity (Trauma Injury Severity Score, Injury Severity Score [ISS],
      Revised Trauma Scale, Glasgow Coma Scale), age, sampling time, shock (systolic
      blood pressure [SBP] < 90 at the scene, transport, and admission; base deficit),
      resource utilization (hospital and intensive care unit length of stay, ventilator
      days) and mortality was examined. Statistical analysis included chi2 tests,
      Wilcoxon rank sum tests, p < 0.05 versus iCa > 1, median (25th-75th percentile),
      and odds ratio (OR). RESULTS: In all, 396 out of 2,367 patients were identified.
      Mortality was significantly increased in the iCa < or = 1 group (26.4% versus
      16.7%, p < 0.05; OR 1.92). Time to death in iCa < or = 1 was significantly
      shorter, 0.50 (0-1) versus 1.0 (0-6) days. Mortality was predicted using iCa < or
      = 1 alone (p < 0.02, OR 3.28), iCa < or = 1 + base deficit (p < 0.02, OR 2.00),
      and base deficit alone (p = 0.06, OR 1.5). Low iCa was associated with SBP < 90
      at the scene and transport (p < 0.01). The incidence of base deficit was higher
      in the iCa < or = 1 group (p < 0.05). CONCLUSIONS: Low iCa is associated with
      prehospital hypotension regardless of age, ISS, or sampling time and is a better
      predictor of mortality than base deficit. Since acidosis reduces calcium binding
      to serum protein and actually increases iCa, the association between base deficit
      and iCa in this study requires further investigation.

PMID- 17033541
TI  - Continuous muscle tissue oxygenation in critically injured patients: a
      prospective observational study.
AB  - BACKGROUND: Despite normalization of vital signs, critically injured patients may
      remain in a state of occult underresuscitation that sets the stage for sepsis,
      organ failure, and death. A continuous, sensitive, and accurate measure of
      resuscitation after injury remains elusive. METHODS: In this pilot study, we
      evaluated the ability of two continuous measures of peripheral tissue oxygenation
      in their ability to detect hypoperfusion: the Licox polarographic tissue oxygen
      monitor (PmO2) and the InSpectra near-infrared spectrometer (StO2). We
      hypothesized that deltoid muscle tissue oxygenation measurements could detect
      patients in "occult shock" who are at increased risk for post-injury
      complications. The study was designed to (1) define values for PmO2 and StO2 in
      patients who by all standard measures appeared to be clinically resuscitated; (2)
      evaluate the relationship between PmO2, StO2 and other physiologic variables
      including mean arterial pressure (MAP), lactate and base deficit (BD); and (3)
      examine the relationship between early low tissue oxygen values and the
      subsequent development of infections and organ dysfunction. Licox probes were
      inserted into the deltoid muscle of critically injured patients after initial
      surgical and radiologic interventions, and transcutaneous StO2 monitors were
      applied over the same muscle bed. PmO2, StO2, and standard physiologic data were
      collected continuously using a multimodal bioinformatics system. RESULTS: Twenty
      eight critically injured patients were enrolled in this study at admission to the
      intensive care unit (ICU). For patients who appeared to be well resuscitated
      (defined as MAP > or = 70 mm Hg, heart rate [HR] < or = 110 bpm, BD > or = -2,
      and partial pressure of arterial oxygen (PaO2) = 80 and 150 mm Hg), the mean PmO2
      was 34 +/- 11 mm Hg and StO2 was 63 +/- 27%. There was a strong relationship
      between PmO2 and BD (p < 0.001) but no significant relationship between StO2 and
      BD. The relationship between PmO2 and StO2 was weak but statistically
      significant. Early low values of both PmO2 and StO2 identified patients at risk
      for infectious complications or multiple organ failure (MOF). In patients who
      were well resuscitated by standard continuous parameters (HR and MAP), low PmO2
      during the first 24 hours after admission (PmO2 < or = 25 for at least 2 hours)
      was strongly associated with the development of infectious complications (Odds
      Ratio = 16.5, 95% CI 1.49 to 183, p = 0.02). CONCLUSIONS: PmO2 is a responsive,
      reliable and continuous monitor of changes in base deficit. Initial low values
      for either PmO2 or StO2 were associated with post-injury complications. PmO2
      monitoring may be useful in identifying patients in the state of occult
      underresuscitation who remain at risk for developing infection and MOF.

PMID- 17033542
TI  - Predicting quality of life six months after traumatic injury.
AB  - BACKGROUND: Many factors are known to impact quality of life (QoL) after injury,
      but predictors of diminished QoL and the time course of recovery remain
      incompletely understood. This study examines predictors and correlates of QoL
      measured by the Short Form-36 (SF-36) one and six months postinjury. METHODS:
      Adults with nonneurologic blunt injury were prospectively enrolled. Demographic,
      injury, and socioeconomic data were collected. Patients were assessed with
      functional and psychologic measures. In all, 196 patients had 1-month data and
      123 had 6-month data available. Scores were compared at each time point and also
      to population norms using t-tests. Multiple regression techniques were used to
      identify associations between the physical and mental component scores (PCS &
      MCS) of the SF-36 and patient characteristics. RESULTS: PCS scores improved
      significantly (32.8 +/- 0.9 versus 41.3 +/- 1.0, p < 0.05) whereas MCS scores
      (47.5 +/- 1.1 versus 47.2 +/- 1.1, p = NS) did not. Both remained significantly
      below population norms. Functional Independence Measure (FIM) at one month was
      predictive of PCS at 6 months. Posttraumatic stress disorder (PTSD) was
      predictive of lower MCS, and depression was associated with poor MCS. Injury
      Severity Score was not associated with PCS or MCS. CONCLUSIONS: Overall physical
      and mental QoL measured by the SF-36 remains significantly below population norms
      6 months after traumatic injury. It is possible to identify patients at risk for
      diminished QoL early during recovery by screening for functional status, PTSD,
      social support, and depression. Interventions to address these areas should be
      further studied with respect to their impact on long-term QoL.

PMID- 17033543
TI  - Longitudinal study of suicide after traumatic injury.
AB  - BACKGROUND: Suicide risk after discharge among trauma patients could be
      influenced by multiple factors. The aim of this study is to establish whether
      patients discharged from a trauma center experience an increased suicide rate and
      whether this can be explained by defined demographic, injury, or alcohol abuse
      risk factors. METHODS: Patients admitted between July 1, 1983, and June 30, 1995,
      and discharged alive from a Level I trauma center (n = 27,399) were followed for
      1.5 to 14.5 years to determine whether they had died. Death determination was
      made by an epidemiologic support service, which had created a repository of death
      certificates. Variables used in the analyses included age, gender, race, Injury
      Severity Score, discharge disposition, mechanism of injury, and alcohol
      toxicology. General and trauma populations were compared using standard mortality
      rates. Risk factors for suicide within the trauma population were explored using
      Pearson's chi2, Mantel-Haenszel chi2, Cox proportional hazards, and Mantel-Cox
      log-rank methodology. RESULTS: Suicide was more common in the trauma than in the
      general population (standard mortality rate = 1.71). This difference may be
      attributed primarily to alcohol use problems. Suicide risk in the trauma
      population increased with age from 25 to 44 years, male gender, Caucasian race,
      and positive alcohol toxicology. Disability (as measured by discharge
      disposition), but not injury severity, also seemed to have an influence on
      suicide rates. CONCLUSION: Interventions that address modifiable risk factors for
      suicide (substance abuse, psychiatric disorders, hopelessness, and social
      isolation) could benefit trauma patients known to be at higher risk for suicide,
      particularly those abusing alcohol.

PMID- 17033544
TI  - The effect of computerized tailored brief advice on at-risk drinking in
      subcritically injured trauma patients.
AB  - BACKGROUND: One-third of injured patients treated in the emergency department
      (ED) have an alcohol use disorder (AUD). Few are screened and receive counseling
      because ED staff have little time for additional tasks. We hypothesized that
      computer technology can screen and provide an intervention that reduces at-risk
      drinking (British Medical Association criteria) in injured ED patients. METHODS:
      In all, 3,026 subcritically injured patients admitted to an ED were screened for
      an AUD using a laptop computer that administered the AUD Identification Test
      (AUDIT) and assessed motivation to reduce drinking. Patients with a positive
      AUDIT (n = 1,139) were randomized to an intervention (n = 563) or control (n =
      576) condition. The computer generated a customized printout based on the
      patient's own alcohol use pattern, level of motivation, and personal factors,
      which was provided in the form of feedback and advice. RESULTS: Most patients
      (85%) used the computer with minimal assistance. At study entry, a similar
      proportion in each group met criteria for at-risk drinking (49.6% versus 46.8%, p
      = 0.355). At 6 months, 21.7% of intervention and 30.4% of control patients met
      criteria for at-risk drinking (p = 0.008). Intervention patients also had a 35.7%
      decrease in alcohol intake, compared with a 20.5% decrease in controls (p =
      0.006). At 12 months, alcohol intake decreased by 22.8% in the intervention group
      versus 10.9% in controls (p = 0.023), but the proportion of at-risk drinkers did
      not significantly differ (37.3% versus 42.6%, p = 0.168). CONCLUSIONS: The
      computer-generated intervention was associated with a significant decrease in
      alcohol use and at-risk drinking. Research is needed to further evaluate and
      adapt information technology to provide preventive clinical services in the ED.

PMID- 17033545
TI  - Is fecal diversion necessary for nondestructive penetrating extraperitoneal
      rectal injuries?
AB  - BACKGROUND: Current management of penetrating extraperitoneal rectal injury
      includes diversion of the fecal stream. The purpose of this study is to assess
      whether nondestructive penetrating extraperitoneal rectal injuries can be managed
      successfully without diversion of the fecal stream. METHODS: This study was
      performed at an urban Level I trauma center during a 28-month period from
      February 2003 through June 2005. All patients who suffered nondestructive
      penetrating extraperitoneal rectal injuries were managed with a diagnosis and
      treatment protocol that excluded fecal stream diversion. Patients were placed in
      one of two management arms based upon clinical suspicion for intraperitoneal
      injury. In the first arm, patients with suspicion for rectal injury and a
      positive clinical examination for intraperitoneal injuries were delivered to the
      operating room for exploratory laparotomy. Proctoscopy was performed before
      exploratory laparotomy. Extraperitoneal rectal injuries were left to heal by
      secondary intention. Intraperitoneal rectal injuries were repaired primarily.
      Patients did not receive fecal diversion or perineal drainage. In the second
      management arm, patients with a negative clinical examination for intraperitoneal
      injury and wounding agent trajectory suspicious for rectal injury underwent
      diagnostic peritoneal lavage (DPL), cystography, and proctoscopy in the emergency
      room. Positive DPL or cystography warranted laparotomy as above. Patients with
      positive proctoscopy alone were admitted and placed on a clear liquid diet.
      Barium enema was performed 5 to 7 days postinjury for all rectal injuries with
      diets advanced accordingly.A matched historic control group of rectal injury
      patients who underwent fecal diversion was compared with the nondiversion
      protocol group. Patients from both groups were matched for penetrating abdominal
      trauma index (PATI), age and mechanism of injury. RESULTS: There were 14
      consecutive patients diagnosed with penetrating rectal injury placed in the
      nondiversion management protocol. Of these, 9 (64%) patients in the nondiversion
      group required laparotomy. The average age in the diversion historical control
      group was 30.5 years and 29.3 years in the nondiversion group. The average PATI
      in the diversion group was 15.3 and 16.1 in the nondiversion protocol group. The
      average length of stay for the diversion and nondiversion groups was 9.8 days
      (range, 7-15) and 7.2 days (range, 4-10), respectively. There were no
      complications associated with rectal injuries in either group. CONCLUSIONS:
      Nondestructive penetrating rectal injuries can be managed successfully without
      fecal diversion. Randomized prospective study will be necessary to assess this
      management method.

PMID- 17033546
TI  - Admission physiology criteria after injury on the battlefield predict medical
      resource utilization and patient mortality.
AB  - BACKGROUND: Medical resources and resource allocation including operating room
      and blood utilization are of prime importance in the modern combat environment.
      We hypothesized that easily measurable admission physiologic criteria and injury
      site as well as injury severity calculated after diagnostic evaluation or
      surgical intervention, would be strongly correlated with resource utilization and
      in theater mortality outcomes. METHODS: We retrospectively reviewed the Joint
      Theater Trauma Registry for all battlefield casualties presenting to surgical
      component facilities during Operation Iraqi Freedom from January to July 2004.
      Data were collected from the composite population of 1,127 battlefield casualty
      patients with respect to demographics, mechanism, presentation physiology (blood
      pressure, heart rate, temperature), base deficit, admission hematocrit, Glasgow
      Coma Score (GCS), Injury Severity Score (ISS), operating room utilization, blood
      transfusion, and mortality. Univariate and multivariate analyses were conducted
      to determine the degree to which admission physiology and injury severity
      correlated with blood utilization, necessity for operation, and acute mortality.
      RESULTS: Univariate analysis demonstrated a significant (p < 0.05) association
      between hypothermia (T < 34 degrees C) and the subsequent requirement for
      operation and mortality. In addition, the outcome variable total blood product
      utilization was significantly correlated with base deficit (r = 0.61), admission
      hematocrit (r = 0.51), temperature (r = 0.47), and ISS (r = 0.54). Using multiple
      logistic regression techniques, blood pressure, GCS, and ISS together
      demonstrated a significant association (p < 0.05) with mortality (area under ROC
      curve = 95%). Multiple linear regression established that blood pressure, heart
      rate, temperature, hematocrit, and ISS had a collective significant effect (p <
      0.05) on total blood product utilization explaining 67% of the variance in this
      outcome variable. CONCLUSION: Admission physiology and injury characteristics
      demonstrate a strong capacity to predict resource utilization in the contemporary
      battlefield environment. In the future, such predictive yield could potentially
      have significant implications for triage and medical logistics in the resource
      constrained environment of war and potentially in mass casualty and disaster
      incidents in the civilian trauma setting which will likely have mechanistic
      similarity with war related injury.

PMID- 17033547
TI  - Tactical surgical intervention with temporary shunting of peripheral vascular
      trauma sustained during Operation Iraqi Freedom: one unit's experience.
AB  - BACKGROUND: Rapidly restoring perfusion to injured extremities is one of the
      primary missions of forward military surgical teams. The austere setting, limited
      resources, and grossly contaminated nature of wounds encountered complicates
      early definitive repair of complex combat vascular injuries. Temporary vascular
      shunting of these injuries in the forward area facilitates rapid restoration of
      perfusion while allowing for deferment of definitive repair until after transport
      to units with greater resources and expertise. METHODS: Standard Javid or Sundt
      shunts were placed to temporarily bypass complex peripheral vascular injuries
      encountered by a forward US Navy surgical unit during a six month interval of
      Operation Iraqi Freedom. Data from the time of injury through transfer out of
      Iraq were prospectively recorded. Each patient's subsequent course at Continental
      US medical centers was retrospectively reviewed once the operating surgeons had
      returned from deployment. RESULTS: Twenty-seven vascular shunts were used to
      bypass complex vascular injuries in twenty combat casualties with a mean injury
      severity score of 18 (range 9-34) and mean mangled extremity severity score of 9
      (range 6-11). All patients survived although three (15%) ultimately required
      amputation for nonvascular complications. Six (22%) shunts clotted during
      transport but an effective perfusion window was provided even in these cases.
      CONCLUSION: Temporary vascular shunting appears to provide simple and effective
      means of restoring limb perfusion to combat casualties at the forward level.

PMID- 17033548
TI  - Long term impact of damage control surgery: a preliminary prospective study.
AB  - BACKGROUND: To evaluate the impact of damage control laparotomy on long term
      morbidity and survival. METHODS: Prospective data were collected on 56
      consecutive trauma patients over a 20-month period (May 2000-January 2002).
      Patients were stratified by mechanism of injury, age, Injury Severity Score, and
      type of injury, temperature at admission, initial blood transfusion volume and
      pH. Initial outcome data included major complications, intensive care unit and
      hospital length of stay, and mortality. Readmission data including number of
      admissions, surgical procedures, and hospital length of stay were then analyzed
      over the subsequent follow-up years (2001-2003). RESULTS: The mean age of the
      study group was 31 +/- 11 years with a mean Injury Severity Score of 33 +/- 13.
      The majority of the patients were male (73%) with a relatively equal number of
      blunt (n = 30) and penetrating injuries (n = 26). Liver injuries (34 [61%]) were
      the most common solid organ injury followed by 22 bowel (39%), 19 spleen (34%),
      11 major vessel (20%), and 7 pancreas (13%) injuries. The mean number of initial
      abdominal surgical procedures was 4.4 +/- 2.2 per patient. The overall mortality
      during the first admission was 27%. Time spent in the intensive care unit and
      hospital length of stay was 17 +/- 13 and 30 +/- 19 days, respectively. There
      were a total of 74 readmissions and 58 subsequent surgical procedures in the 41
      patients who were readmitted. Thirty-one (76%) patients were re-admitted at least
      one time. Infection (n = 19) was the most common reason for readmission followed
      by ventral hernia repair (n = 17) and fistula management (n = 14). There was 0%
      mortality for patients who survived the preliminary hospitalization but required
      readmission. CONCLUSION: Although damage control laparotomy is associated with a
      significant complication and readmission rate, its long term survival and benefit
      is indisputable.

PMID- 17033549
TI  - High frequency oscillatory ventilation for surgical patients with acute
      respiratory distress syndrome.
AB  - BACKGROUND: Numerous studies have suggested that high-frequency oscillatory
      ventilation (HFOV) used as rescue therapy may improve oxygenation in acute
      respiratory distress syndrome (ARDS) patients. The purpose of this study is to
      analyze the efficacy and safety of HFOV in surgical patients with ARDS. METHODS:
      A total of 16 surgical ARDS patients with severe oxygenation failure received
      HFOV, despite aggressive conventional mechanical ventilatory support. Mean airway
      pressure was initially set 3 to 5 cm H2O higher than that for conventional
      ventilation and was subsequently adjusted to maintain oxygen saturation > or =
      90% and FiO2 < or =0.6. Oxygenation, ventilation, and hemodynamic parameters were
      measured during conventional ventilation before initiating HFOV and during HFOV
      support for a total of 40 hours. Other outcome measures included duration of
      HFOV, successful weaning rate, cause of failure, complications, survival rate,
      and cause of death. RESULTS: There was a considerable increase in Pao2/FiO2 ratio
      after 30 minutes, and this increase was maintained after 12 hours of HFOV
      throughout the study. There was a significant decrease in oxygenation index after
      24 hours of HFOV support. There was no significant change in blood pressure
      associated with initiation and administration of HFOV. The successful weaning
      rate from HFOV to conventional ventilation was 75%. The intensive care unit
      survival rate was 43.8% and hospital survival rate was 37.5%. CONCLUSION: High
      frequency oscillatory ventilation was effective and safe in correcting
      oxygenation failure associated with ARDS in surgical patients. Future research is
      warranted to identify the suitable patients, timing, and optimal strategy for
      applying HFOV.

PMID- 17033550
TI  - Evaluation of invasive and noninvasive hemodynamic monitoring in trauma patients.
AB  - OBJECTIVES: The aim of this study was to compare a recently developed and
      improved noninvasive hemodynamic monitoring system with the conventional invasive
      monitoring by pulmonary artery catheterization (PAC) in acute emergency trauma
      patients. METHODS: In a large, university-run, inner city public hospital, we
      monitored 993 trauma patients noninvasively; 262 of these were simultaneously
      monitored with both noninvasive hemodynamic and invasive PAC monitoring. The
      noninvasive monitoring was begun shortly after admission to the emergency
      department and the invasive PAC monitoring was started in the operating room, or
      as soon as the patient arrived in the intensive care unit. Noninvasive monitoring
      included cardiac index (CI) by the IQ or Physio Flow bioimpedance device,
      together with mean arterial blood pressure, heart rate, pulse oximetry (SapO2),
      transcutaneous oxygen (PtcO2), and carbon dioxide (PtcCO2) tensions. We compared
      CI by simultaneous measurements with both invasive and noninvasive methods 907
      times in 262 patients. RESULTS: The CI by thermodilution (CItd) correlated well
      with simultaneous measurements with the bioimpedance (CIbi), r2 = 0.915, r2 =
      0.84, p < 0.001. The bias and precision of simultaneous measurements was -0.070
      +/- 0.47 L/min/m2; agreement was considered satisfactory. In the initial
      resuscitation period of both monitoring systems, the CI, mean arterial blood
      pressure, SapO2, and tissue perfusion (reflected by invasive DO2 and VO2, and by
      noninvasive PtcO2/FiO2 ratio) were higher in survivors than in nonsurvivors,
      whereas heart rate values were higher in the nonsurvivors. We concluded that
      noninvasive hemodynamic monitoring provided a feasible, safe, inexpensive,
      accurate, continuous, on-line real-time graphic displays that are equivalent to
      the essential features of invasive pulmonary artery catheter monitoring.

PMID- 17033551
TI  - Biomechanic study of the human liver during a frontal deceleration.
AB  - BACKGROUND: Mechanisms of hepatic injury remain poorly understood. Surgical
      literature reports some speculative theories that have never been proved. The aim
      of this study was to examine the behavior of the liver during brutal frontal
      deceleration. METHODS: Six trunks, removed from human cadavers, underwent free
      falls at 4, 6, and 8 meters per second (mps). Accelerometers were positioned in
      the two lobes of the liver, in front of the vertebra L2, and in the retro hepatic
      inferior vena cava. Relative motions of the lobes of the liver and of the two
      other anatomic marks were observed. In parallel, numerical simulations of this
      experiment have been performed using a finite element model. RESULTS: In the
      direction of impact, the vertebra L2 had no considerable displacement with the
      inferior vena cava. There was a noteworthy displacement between the two hepatic
      lobes. The left hepatic lobe had a large relative displacement with the vertebra
      L2 and the inferior vena cava. The right hepatic lobe was more stable with the
      vertebra L2 and the inferior vena cava. Numerical simulation of the same protocol
      underlined a rotation effect of the liver to the left around the axis of the
      inferior vena cava. CONCLUSIONS: These results support the surgical data. They
      highlight a crucial zone and explain how dramatic lacerations between the two
      lobes of the liver can occur.

PMID- 17033552
TI  - A prospective evaluation of the value of repeat cranial computed tomography in
      patients with minimal head injury and an intracranial bleed.
AB  - BACKGROUND: Patients with minimal head injury (MHI) and intracranial bleed (ICB)
      detected on cranial computed tomography (CT) scan routinely undergo a repeat
      cranial CT within 24 hours after injury to assess for progression of intracranial
      injuries. While this is clearly beneficial in patients with a deteriorating
      neurologic status, it is of questionable value in patients with a normal
      neurologic examination. The goal of this study was to prospectively assess the
      value of a repeat cranial CT in patients with a MHI and an ICB who have a normal
      neurologic examination. METHODS: A prospective analysis of all adult patients
      admitted to a Level I trauma center after blunt trauma causing a MHI (defined as
      the loss of consciousness or posttraumatic amnesia with a Glasgow Coma Scale
      (GCS) score of greater or equal to 13) and an ICB on the initial cranial CT
      during a 12-month period (July 2002 through July 2003) was performed. All
      patients with MHI were prospectively evaluated and followed until discharge. Data
      collected included demographics, neurologic examination and findings on the
      initial and repeat cranial CT scan. Outcome data included neurologic
      deterioration, neurosurgical intervention, and Glasgow Outcome Scale (GOS) on
      discharge. RESULTS: In all, 161 consecutive patients with MHI and a positive
      cranial CT scan were identified. The initial cranial CT lead to a neurosurgical
      intervention (1 craniotomy, 4 intracranial pressure monitors) in 4% of cases. The
      remaining 130 patients who met inclusion criteria, underwent a repeat cranial CT
      scan within 24 hours postadmission. Ninety nine (76%) patients had a normal
      neurologic examination at the time of their repeat cranial CT. After the repeat
      cranial CT none required immediate neurosurgical intervention or had delayed
      neurologic deterioration related to their head injury. Fifteen patients underwent
      additional neuroradiologic studies but none showed further progression of their
      ICB or lead to a change in management. One patient died from non-traumatic brain
      injury related causes and of the remaining 26 patients, 98% had an overall
      favorable GOS score (> 3) on discharge. In this group of patients with MHI and
      ICB, the negative predictive value of a normal neurologic examination was 100%.
      CONCLUSIONS: Repeat cranial CT, in patients with a MHI and a normal neurologic
      examination, resulted in no change in management or neurosurgical intervention
      and is therefore not indicated. A multicenter prospective study would further
      validate these conclusions, reduce unnecessary CT scans, and likely improve our
      current standard of care in these patients.

PMID- 17033553
TI  - Early prediction of mortality in isolated head injury patients: a new predictive
      model.
AB  - BACKGROUND: To construct a predictive model of survival in isolated head injury
      patients, on the basis of easily available parameters that are independent risk
      factors for survival outcome. METHODS: Trauma registry-based study of head injury
      patients who had no other major extracranial injuries and were not hypotensive at
      admission. A predictive model of probability of death was constructed using
      discriminant analysis, on the basis of admission Glasgow Coma Scale (GCS) score,
      head Abbreviated Injury Score (AIS), age, and mechanism of injury. RESULTS: The
      study included 7,191 patients with head trauma. The overall correct
      classification rate of the proposed predictive model was 94.2% as compared with
      89.0% of the admission GCS score (p < 0.05) and 92.8% of the head AIS (p < 0.05).
      The correct classification rate of the predictive model developed for the severe
      head trauma (GCS score 4-8) patients was 79.9%, as compared with 72.6% using the
      admission GCS score alone or 75.1% (p < 0.05). A one-page, easy to use table
      summarizing the predicted mortality on the basis of GCS score, head AIS,
      mechanism of injury, and age was developed. CONCLUSIONS: The proposed model has a
      significantly better predictive power, especially in severe head trauma, than the
      extensively used GCS and head AIS. A simple table on the probability of death of
      a particular patient based on admission GCS score, head AIS, mechanism of injury
      and age of patient can provide instant information.

PMID- 17033554
TI  - Endothelin-1, inducible nitric oxide synthase and macrophage inflammatory protein
      1alpha in the pathogenesis of stress ulcer in neurotraumatic patients.
AB  - BACKGROUND: To prospectively identify histologically and endoscopically the
      effect of omeprazole on the expression of endothelin-1 (ET-1), inducible nitric
      oxide synthase (iNOS) and macrophage inflammatory protein-1alpha (MIP-1alpha) in
      the gastric mucosa of neurosurgical patients with stress ulcer. METHODS: Twenty
      five patients with severe acute intracranial lesions caused by trauma were
      enrolled in this study. A 40 mg intravenous bolus of omeprazole (OME) was given
      daily for 7 days. The intragastric pH was continuously recorded for 24 hours on
      day 1 and 8. Endoscopic evaluation of the gastric corpus, antrum, and duodenal
      bulb was performed in the ICU, within 24 hours after brain injury, and at follow
      up on the 7th day after admission. Paired biopsies were obtained for histologic
      examinations and immunohistochemical analysis was performed using a LSAB method
      for MIP-1alpha, ET-1, and iNOS. RESULTS: There were 72% and 70% of gastroduodenal
      mucosal lesions at the initial and follow-up endoscopies, respectively. However,
      the severity of mucosal lesions showed significant improvement in most patients
      at follow-up (p < 0.05). Mean percentages of time intragastric pH were greater
      than or equal to 4.0 were 20 +/- 11% and 70 +/- 17% on day 1 and 8, respectively
      (p < 0.05). The incidences of ET-1, iNOS and MIP-1alpha expression were not
      significantly different between the patients before and after OME prophylaxis.
      CONCLUSIONS: Prophylactic OME is effective in reducing the severity of stress
      ulcerations in severe neurotraumatic patients. High incidence of tissue ET-1
      expression combined with increased activity of iNOS and MIP-1alpha may be
      responsible for the gastric mucosal injury. We also show that OME fails to
      counter the enhancement in the mucosal expression of ET-1, iNOS, and MIP-1alpha
      caused by severe brain damage.

PMID- 17033555
TI  - Bradykinin B2 receptor antagonism with LF 18-1505T reduces brain edema and
      improves neurological outcome after closed head trauma in rats.
AB  - BACKGROUND: We evaluated the effect of LF 18-1505T, a novel nonpeptide bradykinin
      type-2 receptor antagonist, on brain edema and neurologic severity score (NSS)
      after closed head trauma (CHT). METHODS: There were 132 rats anesthetized and
      assigned for sham or CHT; infusion of saline or LF 18-1505T (0.3, 1, 3, 10, or 30
      microg x kg x min); and determination of neurologic outcome (brain water content
      and NSS) or physiologic variables (blood pressure, glucose concentration, etc.).
      RESULTS: Post-CHT brain water content was less with LF 18-1505T doses of 3 and 10
      microg x kg x min (80.1 +/- 3.8 through 81.6 +/- 2.6%, mean +/- SD) than in the
      untreated group (84.6 +/- 1.9%, p < 0.01). Post-CHT NSS improved with doses of 3,
      10, and 30 microg x kg x min (median, 7; range, 0-12 through median, 10; range, 8
      18) as compared with that in the untreated group (median, 17; range, 14-23; p <
      0.05). LF 18-1505T with or without CHT did not significantly alter physiologic
      variables. CONCLUSIONS: LF 18-1505T decreased brain edema and improved neurologic
      status after CTH in rats without significantly altering physiologic values.

PMID- 17033556
TI  - Long-term follow-up of Iranian veteran upper extremity amputees from the Iran
      Iraq war (1980-1988).
AB  - BACKGROUND: Despite their frequency, there are limited reports concerning long
      term follow up of upper limb amputation among battle-injured patients, which
      occurred at a young age. The purpose of this study was to evaluate how well these
      patients function years after their injury. METHODS: The study consisted of a
      thorough assessment and examination and review of the history and war time
      medical records of 25 Iranian veteran amputees from imposed Iran-Iraq war with a
      comprehensive survey including a detailed questionnaire. Information was analyzed
      and compared with limited similar reports in the literature. RESULTS: Out of 200
      war amputees there were 25 unilateral upper limb amputees; all others were lower
      limb amputees. The average age at the time of injury was 23.06 years, average age
      at follow-up was 41.55 years, and the average time between injury and follow-up
      was 17.5 years. The most common level of amputation was below elbow (40%), and
      the most common cause of war injury was artillery shells, mortar or rocket
      shells. The prevalence of clinical symptoms of phantom sensation, phantom pain,
      phantom movement and stump pain were; 64%, 32%, 20%, 24%, respectively. All
      patients were married (100%) and had children except one case (96%). Sixty
      percent of patients were employed. Thirty-six percent had a documented
      psychiatric history ranging from minor depression to posttraumatic stress
      disorders. CONCLUSION: The study showed-despite long period of time between war,
      amputation, and follow-up-there is a significant rate of amputation symptoms, but
      on the other hand good family and social function of the patients.

PMID- 17033557
TI  - Results of total elbow arthroplasty in the treatment of distal humerus fractures
      in elderly Asian patients.
AB  - BACKGROUND: Distal humerus fractures in elderly patients are difficult to treat
      as these fractures are often complicated by varying degrees of comminution intra
      articular involvement and osteoporosis. We retrospectively reviewed the results
      of primary total elbow arthroplasty in the treatment of distal humerus fractures
      in seven patients followed for a minimum of 1 year. METHODS: Between July 2000
      and June 2002, seven patients with distal humerus fractures were treated
      electively with total elbow arthroplasty using the semiconstrained Coonrad-Moorey
      elbow replacement prostheses. The Mayo Elbow Performance Score was used to assess
      the outcomes. RESULTS: The mean age of our patients was 72.9 years. The mean
      duration of postoperative hospitalization stay was 7.6 days. The average length
      of follow up was 24.9 months. Six of these patients had no pain, and one patient
      had mild pain. The mean arc of flexion was 88.6 degrees. Six elbows had excellent
      results, while 1 elbow had good result. The mean Mayo score was 94.3 points. One
      elbow developed blisters postoperatively but resolved with dressings and
      antibiotics. CONCLUSIONS: Our review suggests that total elbow arthroplasty can
      give good to excellent short term results when used in the treatment of distal
      humerus fractures in elderly Asian patients.

PMID- 17033558
TI  - Effectiveness of completely round nails with both-ends-threaded locking screws
      for tibial shaft fractures.
AB  - BACKGROUND: Completely round nails, in contrast to conventional locked nails with
      surface grooves, for postoperative endosteal revascularization may increase the
      nail rigidity and decrease the manufacture cost. Both-ends-threaded screws with
      higher fatigue strength require smaller nail holes and can further increase the
      mechanical strength of the nails. METHODS: In this study, both-ends-threaded
      locking screws were used to treat 68 tibial fractures, including 56 acute
      fractures in 54 patients and 12 nonunions in 12 patients. There were 41 men and
      25 women with a mean age of 39.6 years, and the average follow-up was 24 months.
      For acute fractures, there were 11 type I, 9 type II, 5 type IIIA, and 3 type
      IIIB open fractures. Acute fractures were treated with closed nailing. Five
      hypertrophic nonunions were treated with closed exchanged nailing, and seven
      oligotrophic nonunions were treated with open nailing and iliac bone grafting.
      RESULTS: With a single nailing procedure, 53 acute fractures and all nonunions
      achieved union with mean times of 17.4 weeks and 18.4 weeks, respectively. Three
      patients underwent exchange nailing and bone grafting and had eventual fracture
      union. Three fractures with compartment syndrome were treated with fasciotomy.
      Deep infection occurred in two open fractures but was successfully treated. Nail
      breakage occurred in one distal fracture and screw backout occurred in another,
      but fracture union was not affected. Recovery of joint motion was essentially
      normal in patients without knee or ankle injury. CONCLUSIONS: This study showed
      that completely round nails with both-ends-threaded locking screws could
      effectively treat tibial fractures. Completely round nails have the advantages of
      high mechanical strength and low manufacturing cost.

PMID- 17033559
TI  - Overdistraction of the fracture eases reduction in delayed femoral nailing:
      results of intraoperative force measurements.
AB  - BACKGROUND: (Initial) primary external fixation of femoral shaft fractures
      followed by secondary intramedullary nailing is a concept of damage control
      orthopedics. We hypothesized that external fixation with overdistraction of the
      fracture might reduce reduction forces and shorten reduction time during the
      secondary nailing. METHODS: An experimental study on seven patients with eight
      fractures of the femoral shaft was conducted. Intraoperative reduction forces
      were determined in all patients using a load cell. The amount of distraction was
      measured on the latest radiographs before nailing. The reduction time was
      recorded as an indirect indicator of the intricacy of reposition. Reduction
      forces and reduction times were compared between those fractures fixed with
      shortening (Group A) and those fixed in distraction (Group B). RESULTS: Three
      femurs showed some shortening and five femurs showed some distraction within the
      fracture. The maximum measured distraction force along the shaft axis was 396 N.
      On average the maximal force was 336 N (+/- 51.9 N) in Group A and 200 N (+/-
      43.1 N) in Group B. This difference is statistically significant (p = 0.007). The
      average reduction time was 28.3 minutes (+/- 21.8 minutes) in Group A and 5.8
      minutes (+/- 4.0 minutes) in Group B. This difference shows a trend toward
      significance (p = 0.056). CONCLUSION: Fracture shortening leads to higher
      restraining forces and consequently prolonged reduction time in delayed nailing.
      Overdistraction should be performed as soon as possible under careful soft-tissue
      monitoring.

PMID- 17033560
TI  - Three-dimensional analysis of pelvic volume in an unstable pelvic fracture.
AB  - BACKGROUND: A model was developed to predict changes in pelvic volume associated
      with increasing pubic diastasis in unstable pelvic fractures. METHODS: Intact and
      postfracture pelvic volumes were calculated in 10 cadavers using computerized
      axial tomography (CT). The true pelvis was assumed to be either a sphere, a
      cylinder, or a hemi-elliptical sphere. Using the appropriate equations for
      calculating the volume of each of these shapes, pelvic volume was predicted and
      then compared with the measured values. RESULTS: The observed volume changes
      associated with increasing pubic diastasis were much smaller than previously
      reported. The mean difference between the measured and predicted volume was 20.0
      +/- 9.9% for the sphere, 10.7 +/- 6.5% for the cylinder, and 4.5 +/- 5.9% for the
      hemi-elliptical sphere. The differences between these means were statistically
      significant (p < 0.001). CONCLUSIONS: This data suggests that the hemi-elliptical
      sphere best describes the geometric shape of the true pelvis and better predicts
      quantitative changes in pelvic volume relative to an increasing pubic diastasis
      as the radius has little effect on the change in volume. Due to the small changes
      in volume observed with increasing diastasis, factors other than the absolute
      change in volume must account for the clinically observed effects of emergent
      pelvic stabilization.

PMID- 17033561
TI  - Compartment pressures, limb length changes and the ideal spherical shape: a case
      report and in vitro study.
AB  - BACKGROUND: Changes in compartment pressures have been noted during traction,
      reduction, and intramedullary fixation of fractures. Changes in limb length and
      compartment volumes are suspected contributing factors. Pressure and volume
      changes are known to be related in animal models. If an acute increase in limb
      length can adversely affect compartment pressures, reversal or delay of such an
      increase in length may be of value in the treatment and prevention of compartment
      syndromes. METHODS: A clinical example is presented in which a documented
      anterior compartment syndrome was successfully treated by deliberate loss of
      fracture reduction, without fasciotomy. Fracture reduction was later restored
      when swelling subsided. Anterior compartment pressures were recorded in response
      to limb length changes in osteotomized cadaver limbs stabilized with external
      fixation. RESULTS: The pressure in the anterior compartment varies directly with
      acute changes in the length of the leg, in an experimental model. Mathematical
      analysis indicates that available volume within a compartment varies inversely
      with acute changes in its length. CONCLUSIONS: Fracture reduction that restores
      the length of an acutely injured extremity may increase pressure in the
      compartments by decreasing available volume. Deliberate loss of reduction can
      decrease pressure in the compartments, offering a potential alternative to
      fasciotomy in the care of compartment syndrome in cautiously selected, monitored
      patients. Early stabilization without reduction, followed by delayed reduction,
      may be preferable during treatment of fractures prone to compartment syndrome.
      Decreased available compartment volume may contribute to compartment syndrome
      after distraction with intramedullary rods or skeletal traction.

PMID- 17033562
TI  - Hyperbaric oxygen therapy in orthopedic conditions: an evaluation of safety.
AB  - BACKGROUND: Because of the documented cellular and biochemical benefits of
      hyperbaric oxygen (HBO), HBO therapy is applied now with increasing frequency to
      various orthopedic conditions. Many traumatologists and orthopedic surgeons might
      refer their patients for adjuvant HBO therapy. However, the potential risks and
      risk-benefit ratio have often been underemphasized in therapeutic trials.
      METHODS: From October 2002 to September 2004, 240 patients with a total of 4,638
      treatments received HBO therapy at the hyperbaric medicine center of our
      institution on an identical treatment protocol. HBO therapy patient treatment
      logs were reviewed to analyze the incidence of complications during HBO
      treatment. RESULTS: The overall incidence of complications was 1.83%. Over 94% of
      treatment complications were mild to moderate and designated as minor
      complications; fewer than 6% were severe or life threatening and designated as
      major complications. The incidence of major complications (central nervous system
      [CNS] oxygen toxicity in this series) was 0.109%. There was no mortality. Two
      patients with unusual presentation of CNS oxygen toxicity were observed during
      the study period. CONCLUSIONS: HBO therapy in orthopedic conditions is considered
      as a safe treatment because of a very low complication rate; however, analysis of
      patients with CNS oxygen toxicity revealed its unpredictability and
      inevitability. Although it is common sense that patients who develop a seizure in
      the hospital need help from the medical staff, it cannot be done in a monoplace
      hyperbaric chamber because of pressure unequalization. Therefore, a multiplace
      chamber equipped with an antechamber for medical contingency is possibly the
      better facility in consideration of safety.

PMID- 17033563
TI  - The effect of hypoxemic resuscitation of hemorrhagic shock on hemodynamic
      stabilization and inflammatory response: a pilot study in a rat experimental
      model.
AB  - BACKGROUND: Resuscitation of hemorrhagic shock is associated with tissue injury.
      The effect of hypoxemia during resuscitation was investigated. METHODS: Shock was
      induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and
      maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to
      receive either normoxemic (controls, FiO2 = 21%, n = 14) or hypoxemic (HypRes,
      FiO2 = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was
      assessed through hemodynamic and inflammatory parameters. Another nine rats
      served to correlate different FiO2 to the corresponding PaO2. RESULTS: At 60
      minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008).
      The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1
      2.1) versus 3.1 (2.4-4.3) micromol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL,
      (p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values
      were similar between groups. FiO2 of 12% induced only a mild hypoxemia (PaO2
      approximately 80 mm Hg). CONCLUSIONS: Even mild hypoxemia during resuscitation of
      shock leads to effective hemodynamic stabilization.

PMID- 17033564
TI  - Impact of severity of local soft-tissue trauma on long-term manifestation of
      microcirculatory and microlymphatic dysfunctions.
AB  - BACKGROUND: The present study aimed at quantitatively evaluating the impact of
      severity of local trauma on manifestation of soft-tissue injury-associated
      microcirculatory and microlymphatic dysfunctions in a chronic model that allowed
      repeated analyses by intravital fluorescence microscopy. METHODS: C57BL/6 mice
      were chronically instrumented with dorsal skinfold chambers and subjected to mild
      (180 J/m2, n = 6), moderate (270 J/m2, n = 6), or severe trauma (450 J/m2, n = 6;
      540 J/m2, n = 6). Nontraumatized animals served as controls (sham; n = 8).
      Intravital microscopy was performed before and at 5 minutes, 1 hour, 8 hours, 24
      hours, 3 days, and 5 days after trauma, and included the analysis of (1) blood
      and lymph microvessel rupture, (2) hematoma formation and lymph leakage, (3)
      arteriolar and venular constriction, (4) capillary perfusion failure, (5)
      arteriolar and venular leukocyte adhesion, and (6) interstitial edema formation.
      RESULTS: Mild trauma did not induce any changes of microcirculatory and
      microlymphatic functions. Moderate trauma did not affect lymphatics but provoked
      arteriolar constriction, capillary perfusion failure, leukocyte-endothelial cell
      interactions, and minor blood vessel ruptures with hematoma formation. These
      alterations, however, recovered within the first 24 hours after trauma. Severe
      trauma also did not affect the lymphatic microvasculature, but resulted in
      massive hematoma formation, arteriolar constriction, and capillary perfusion
      failure, which was associated with marked arteriolar and venular leukocyte
      recruitment and edema formation, and which did not recover to normal over a 5-day
      observation period. CONCLUSION: Only severe trauma of > 450 J/m2 provokes
      irreversible microcirculatory dysfunction in soft tissue, however, without
      affecting the integrity of lymphatic microvessels. Of interest, trauma-induced
      microcirculatory alterations are neither dominated solely by microcirculatory
      dysfunction nor by leukocytic inflammation. Instead, both pathologies develop in
      parallel, generating a vicious circle, which may be responsible for the
      compromised healing of severely traumatized soft tissue frequently observed in
      clinical practice.

PMID- 17033565
TI  - Lung injury and recovery after exposure to blast overpressure.
AB  - BACKGROUND: A critical immediate determinant of survival after exposure to blast
      overpressure (BOP) is pulmonary damage, but mechanisms of injury and the course
      of recovery are not well understood. The objective of this study was to
      characterize the progression of oxidative and inflammatory responses in lungs as
      well as the activation of consequent protective mechanisms after exposure to
      medium intensity BOP. METHODS: Rats were exposed to a moderate (approximately 120
      kPa) level of BOP in a pneumatically driven shock tube. At different times (2-192
      hours) after exposure, lungs were examined for pathologic signs of injury,
      markers of inflammatory responses, and indicators of oxidative and nitrative
      damage. RESULTS: The results showed a postblast activation of inflammatory
      response (increase of myeloperoxidase activity, CINC-1, ICAM-1, and iNOS),
      increase in protein oxidation and nitration, and development of gross diffused
      hemorrhage in lungs. The initial phase of lung damage that peaked at 24 to 48
      hours after exposure to BOP was followed by gradual dissolution of inflammation
      and oxidation that were complete by 192 hours. Resolution of morphologic damage
      and inflammation in lungs concurred with activation of expression of antioxidant
      enzymes heme oxygenase-1 (HO-1) and manganese superoxide dismutase (MnSOD).
      Plasma level of gelsolin, a marker of acute lung damage was decreased at 24 hours
      postblast and later returned to the control level. CONCLUSIONS: The study shows
      the role of adaptive anti-oxidant and anti- inflammatory mechanisms in lung
      recovery after injury caused by exposure to BOP.

PMID- 17033566
TI  - Simulation training for a mass casualty incident: two-year experience at the Army
      Trauma Training Center.
AB  - BACKGROUND: Civilian and military mass casualty incidents (MCI) are an
      unfortunate reality in the 21st century, but there are few situational training
      exercises (STX) to prepare for them. To fill this gap, we developed a MCI STX for
      U.S. Army Forward Surgical Teams (FST) in conjunction with the U.S. Army Trauma
      Training Center. METHODS: After a standardized briefing, each FST has 60 minutes
      to unpack, setup, and organize a standard equipment cache into an emergency room,
      operating room, and intensive care unit. In an adjacent room, five anesthetized
      swine are prepared with standardized, combat-relevant injuries. The number and
      acuity of the total casualties are unknown to the FST and arrive in waves and
      without warning. A realistic combat environment is simulated by creating resource
      limitations, power outages, security breaches, and other stressors. The STX
      concludes when all casualties have died or are successfully treated. FSTs
      complete a teamwork self-assessment card, while staff and FST surgeons evaluate
      organization, resource allocation, communication, treatment, and overall
      performance. Feedback from each FST can be incorporated into an updated design
      for the next STX. RESULTS: From 2003-2005, 16 FSTs have completed the STX. All
      FSTs have had collapses in situational triage, primary/ secondary surveys, and/or
      ATLS principles (basic ABCs), resulting in approximately 20% preventable deaths.
      CONCLUSIONS: We concluded (1) a MCI can overwhelm even combat- experienced FSTs;
      (2) adherence to basic principles of emergency trauma care by all FST members is
      essential to effectively and efficiently respond to this MCI; (3) by
      prospectively identifying deficiencies, future military or civilian performance
      during an actual MCI may be improved; and (4) this MCI STX could provide a
      template for similar programs to develop, train, and evaluate civilian surgical
      disaster response teams.

PMID- 17033567
TI  - Do trauma centers have the capacity to respond to disasters?
AB  - BACKGROUND: Concern has been raised about the capacity of trauma centers to
      absorb large numbers of additional patients from mass casualty events. Our
      objective was to examine the capacity of current centers to handle an increased
      load from a mass casualty disaster. METHODS: This was a cross-sectional study of
      Level I and II trauma centers. They were contacted by mail and asked to respond
      to questions about their surge capacity as of July 4, 2005. RESULTS: Data were
      obtained from 133 centers. On July 4, 2005 there were a median of 77 beds
      available in Level I and 84 in Level II trauma centers. Fifteen percent of the
      Level I and 12.2% of the Level II centers had a census at 95% capacity or
      greater. In the first 6 hours, each Level I center would be able to operate on 38
      patients, while each Level II center would be able to operate on 22 patients.
      Based on available data, there are 10 trauma centers available to an average
      American within 60 minutes. Given the available bed capacity, a total of 812 beds
      would be available within a 60-minute transport distance in a mass casualty
      event. CONCLUSIONS: There is capacity to care for the number of serious non
      fatally injured patients resulting from the types of mass casualties recently
      experienced. If there is a further continued shift of uninsured patients to and
      fiscally driven closure of trauma centers, the surge capacity could be severely
      compromised.

PMID- 17033568
TI  - Primary trauma diversion: initial experience in Hong Kong.
AB  - BACKGROUND: Trauma is a leading cause of death and loss of workdays in Hong Kong.
      Reports have suggested that timely provision of care in dedicated trauma centers
      can improve outcomes. Until recently, ambulances were required to take trauma
      patients to the nearest hospital's emergency department. This paper reports on
      the initial experience of primary trauma diversion from scene to a dedicated
      trauma center in Hong Kong. METHODS: This prospective study involved the
      establishment of primary trauma diversion in the area served by Alice Ho
      Nethersole Hospital (AHNH), a general hospital in the New Territories. Trauma
      patients who fulfilled diversion criteria were taken directly to the Prince of
      Wales Hospital (PWH) in Shatin, a university teaching hospital and trauma center
      for the area. Data were collected to determine the change in time to definitive
      care for trauma patients and an impact analysis on PWH services was performed.
      RESULTS: There were 60 patients who underwent primary trauma diversion and 35
      patients underwent secondary diversion after initial treatment at AHNH. This
      represented two extra trauma patients per week at PWH. Median Injury Severity
      Score (ISS) was 9 and 52% of patients had been involved in a traffic crash. Of
      eligible patients, 76% (69 out of 91) diverted correctly according to protocol.
      Primary trauma diversion patients reached definitive care 97 minutes faster than
      patients undergoing secondary diversion. CONCLUSION: Primary trauma diversion is
      feasible in Hong Kong and means that patients reach definitive care 97 minutes
      faster than going to the nearest hospital. Primary trauma diversion protocols
      should be extended throughout Hong Kong.

PMID- 17033569
TI  - Impaired generic health status but perception of good quality of life in
      survivors of burn injury.
AB  - BACKGROUND: Although it is recognized that burn survivors face a variety of
      challenges related to physical, psychologic and social late-effects of their
      injury, the impact of thermal injury on the lives of patients is not fully
      understood. To learn more about burn patient needs and to obtain information
      relevant to the design of clinical programs for treatment and aftercare, self
      reports on how burn patients perceive their health and quality of life may be of
      significant value. METHODS: The generic health status (evaluated by SF-36) and
      overall quality of life (evaluated by the Quality of Life Scale [QOLS]) of 95
      adult burn patients (total body surface area burned = 18.5 +/- 14.2% [mean +/-
      SD]; 82.1% men) were assessed 47.0 +/- 23.8 months postburn and compared with
      population norms. RESULTS: The burn patient generic health status was
      significantly poorer than expected from general population scores, with reduced
      scores in the Physical Function (p < 0.001), Role Physical (p < 0.01), General
      Health (p < 0.001), Social Function (p < 0.001), and Role Emotional (p < 0.001)
      domains of the SF-36. Despite their reduced health status, overall quality of
      life was perceived as good, with QOLS scores similar to those of the general
      population. Patients living alone, unemployed, having nonburn physical illness,
      psychologic disorders, chronic pain, or having sustained full thickness injuries
      were found to be at particular risk. CONCLUSIONS: Forty-seven months postinjury,
      burn patients still experienced a significant reduction of generic health,
      reporting limitations related to both physical and psychosocial SF-36 domains. On
      the other hand, the patients as a group reported overall quality of life similar
      to that of the norm population, suggesting that they were able to feel
      satisfaction with their new situation of life. Identification of several risk
      factors for reduced generic health status and overall quality of life support the
      need for specialized multidisciplinary aftercare for burn patients.

PMID- 17033570
TI  - Chirurgica Taurina: a 10-year experience of bullfight injuries.
AB  - BACKGROUND: Despite recent efforts to improve medical treatment for injured
      bullfighters, including the foundation of a scientific society for bullfight
      injuries, serious injuries, in particular in villages and smaller arenas, still
      do occur. We are not aware of any series in the English literature that aimed to
      study the specific mechanisms, types, and outcomes of these injuries. METHODS: A
      review of the trauma registry of injured bullfighters who suffered any type of
      trauma during bullfighting and received emergency therapy by the Surgical Trauma
      Services between 1994 and 2004 at the Plaza de Toros Nuevo Progreso, Guadalajara,
      Mexico. RESULTS: In all, 68 out of 750 bullfighters (9.06%) required emergency
      assistance during bullfighting. Trauma to the upper and lower extremity was most
      common (66%), followed by injuries to the inguinal (8%) and perineal area (7%).
      Extremity injuries included penetrating wounds requiring operative debridement in
      64% of cases, articular dislocations in 4%, closed fractures in 4%, and open
      fractures in 1% of cases. Major vascular injuries occurred in 5% of the cases.
      Penetrating inguinal and penetrating perineal injuries were associated with major
      vascular injuries to the femoral vessels, necessitating operative repair in 33%
      of the cases. CONCLUSION: A considerable risk of serious, life-threatening
      injuries is inherent to bullfighting. Penetrating inguinal and perineal trauma
      with injury to the femoral vessels represents a specific, potentially fatal
      injury. A low threshold for exploration of these penetrating injuries in injured
      bullfighters is associated with a favorable outcome. Appreciation of the unique
      mechanisms and types of injuries related to bullfighting should lead to target
      intervention and help the evolvement of improved emergency treatment in organized
      bullfighting.

PMID- 17033571
TI  - Accidental foot burns in children from contact with naturally heated surfaces
      during summer months: experience from a regional burn center.
AB  - BACKGROUND: Foot burns in children often result from contact with heated surfaces
      due to high ambient temperatures during summer in the southwestern United States.
      The objective of this study was to describe the unique cause and clinical
      characteristics of this type of injury. METHODS: A retrospective review of
      medical records of pediatric patients presenting with contact burns of the foot
      in Arizona Burn Center, which is the third largest burn center in the United
      States. Participants included children 5 years and under who were treated for
      pedal burns during a 5-year period between January 2000 and August 2005. RESULTS:
      Seventy-four children with contact burns of the foot were treated of which 34
      (46%) were from naturally heated surfaces. When compared with those who sustained
      pedal burns as a result of contact with other hot objects, children with burns
      from naturally heated surface more commonly had bilateral (82.4%), second degree
      (82.4%) burns involving primarily the plantar surface (94.1%) of the foot and the
      injury usually occurred in the peak of the summer. Also, physical abuse was more
      commonly suspected in this group. CONCLUSION: Contact with a hot surface during
      summer months is a dominant cause of foot burns in small children in the
      southwestern United States with characteristic clinical presentation and calls
      for preventive educational interventions.

PMID- 17033572
TI  - Aortic rupture in high-speed skiing crashes.
AB  - BACKGROUND: New equipment and techniques in winter sports, such as carving skis
      and snowboards, have brought up new trauma patterns into the spectrum of leisure
      trauma. The injuries resemble high-energy trauma known from road crashes. The aim
      of the present study was to assess the incidence of acute traumatic descending
      aortic rupture in recreational skiing-crashes. MATERIAL: Between January 1995 and
      December 2004, 22 patients were admitted to our hospital for aortic rupture. Four
      patients had skiing crashes (18.2%). Mean age was 31 years, all patients were
      male. In two cases, aortic rupture was associated with fractures of the upper and
      lower extremities. One patient additionally had a cerebral contusion with an
      initial Glasgow Coma Scale score of 13. In two patients, isolated aortic rupture
      was diagnosed. RESULTS: Two patients were treated by graft interposition, and one
      by endograft. One patient arrived under mechanical resuscitation without blood
      pressure. He died at admission. He had been observed for 5 hours in another
      hospital, complaining of severe intrascapular back pain, before transport to our
      trauma unit for unknown bleeding. In the other three cases, treatment was
      successful. CONCLUSION: Rescue services and paramedics should be aware of this
      new type of injury. Acute aortic rupture has to be considered as possible injury
      in high velocity skiing crashes.

PMID- 17033573
TI  - Damage control surgery prior to organ harvesting.

PMID- 17033574
TI  - Cause of post-traumatic hydrocephalus because of traumatic aqueduct obstruction
      in two cases.

PMID- 17033575
TI  - Relapsing altered mental status secondary to a meprobamate bezoar.

PMID- 17033576
TI  - Hemorrhage into a pancreatic lymphangioma after blunt trauma mimicking a post
      traumatic pancreatic pseudocyst.

PMID- 17033577
TI  - Massive traumatic extrapleural hematoma mimicking hemothorax: a potential pitfall
      of penetrating chest trauma.

PMID- 17033578
TI  - Laryngeal injuries from a full face helmet: a report of two cases.

PMID- 17033579
TI  - Safety belt use by law enforcement officers on reality television: a missed
      opportunity for injury prevention?
AB  - BACKGROUND: Although safety belt usage rates are increasing nationwide, motor
      vehicle crashes (MVCs) remain a leading cause of death for young people and are
      emerging as a leading cause for police officers specifically. A content analysis
      was performed on the television show, COPS, to determine on-air safety belt usage
      rates. METHODS: A sample of 63 unique episodes of the reality-based television
      series, COPS, was viewed during a 4-month period (September 1, 2005 to January 1,
      2006). Episodes had original airing dates ranging from 1990 to 2004. Safety belt
      usage status was determined per police officer per driving scene (N = 250). A
      driving scene represented a continuous trip (start to finish) with a total on
      camera time exceeding 5 seconds. Scenes with indeterminate safety belt status
      were excluded. High-speed driving, officer gender, and officer race were also
      recorded. RESULTS: Of the 203 scenes included, 77 (38%) demonstrated safety belt
      usage. High-speed driving scenes had higher safety belt usage rates compared with
      low-speed (48% versus 29%, p = 0.005). More contemporary episodes (1999 to 2004)
      had higher safety belt usage rates as well (51% versus 28%, p = 0.001). Officer
      gender and race revealed no significant differences in safety belt usage rates (p
      = 0.930 and p = 0.900, respectively). CONCLUSIONS: In this popular, reality-based
      television series, safety belt usage by police officers is extremely low. These
      findings suggest the need to increase safety belt usage by police officers,
      especially those filmed for television.

PMID- 17033580
TI  - Surgical management of lower cervical spine fracture in ankylosing spondylitis.

PMID- 17033581
TI  - Fixation of mesh in large flank hernias as a result of extensive muscular
      avulsion from seatbelt injuries.

PMID- 17033582
TI  - Blunt injury to the thyroid gland: proposed classification and treatment
      algorithm.
AB  - BACKGROUND: Traumatic hemorrhage of the thyroid gland is a rare injury with few
      published case reports. Surgical and nonsurgical management have been advocated
      but there is no consensus of opinion. METHODS: This study is a retrospective
      review of published case reports including two own cases. A classification and an
      algorithm for diagnosis and treatment of thyroid gland injuries is proposed.
      RESULTS: A literature review reveals 16 case reports. Of these, 11 patients
      underwent neck exploration for control of hemorrhage and resection of the
      associated thyroid abnormality while 5 patients were conservatively managed. Of
      note is the fact that 10 of the 16 patients (63%) had pre-existing thyroid
      disease. These 10 patients constituted (91%) of the group requiring surgical
      treatment. CONCLUSION: Our proposed classification and algorithm offers
      management guidelines for this rather rare injury. Conservative treatment may be
      successful in selected patients with lower grade injuries and without concomitant
      thyroid disease.

PMID- 17033583
TI  - Rescue treatment with recombinant factor VIIa is effective in patients with life
      threatening bleedings secondary to major wound excision: a report of four cases.
AB  - Major burn wound excision is associated with excessive perioperative blood loss.
      Treatment of massive microvascular bleeding represents a special problem in the
      burn setting, characterized by extensive damage at the capillary level, and
      resulting in a profound blood loss; which together with the consumptive states
      makes adequate replacement therapy with coagulation factors and platelets
      difficult. We described our experience with rescue treatment with rFVIIa in four
      patients undergoing major wound excision, developing life-threatening
      perioperative bleeding, and not responding to conventional therapy. Hemostasis
      was achieved within 15 minutes of intravenous rFVIIa administration, at a dose of
      100 microg/kg, in all patients. No treatment-related adverse events, in
      particular, no thromboembolic events were observed. We conclude that rFVIIa may
      be an effective hemostatic treatment for patients undergoing major wound excision
      developing life-threatening bleedings.

PMID- 17033584
TI  - Isolated gastric injury after blunt abdominal trauma.

PMID- 17033585
TI  - Hepatic artery avulsion secondary to blunt abdominal trauma.

PMID- 17033587
TI  - Abdominal computed tomography and the placement of inferior vena caval filters.

PMID- 17033588
TI  - Silver-coated dressing acticoat caused raised liver enzymes and argyria-like
      symptoms in burn patient.

PMID- 17033589
TI  - Improper use of the term "shrapnel".

PMID- 17033591
TI  - Development and initial psychometric evaluation of the participation measure for
      post-acute care (PM-PAC).
AB  - OBJECTIVE: To evaluate a patient-reported participation measure constructed
      within the framework of the International Classification of Functioning,
      Disability, and Health. DESIGN: The Participation Measure for Post-Acute Care (PM
      PAC) contains 51 items that assess participation in nine domains: mobility; role
      functioning; community, social, and civic life; domestic life/self-care; economic
      life; interpersonal relationships; communication; work; and education. Self
      reported data were collected by interview with 395 noninstitutionalized
      rehabilitation patients. Psychometric analyses were conducted to test assumptions
      underlying the scaling and scoring of PM-PAC scales and to evaluate reliability
      and validity. RESULTS: In general, analyses supported assignment of items to
      hypothesized scales. However, the community, social, and civic life,
      interpersonal relationships, and communication domains were highly correlated.
      Item response theory models indicated that items were directed primarily at
      people with worse than average limitations in participation than the average
      patient in this rehabilitation sample. Test and retest scale scores did not
      differ significantly (intraclass correlation coefficient range, 0.61-0.86).
      Groups with more severe conditions scored worse on PM-PAC scales, as
      hypothesized. CONCLUSIONS: PM-PAC is a promising new measure of patient-reported
      participation as defined by the International Classification of Functioning,
      Disability, and Health. Information about PM-PAC items from this study will be
      useful in developing a computerized, adaptive measure of participation.

PMID- 17033592
TI  - Prognostic factors of activity limitation and discharge destination after stroke
      rehabilitation.
AB  - OBJECTIVE: The aim of this study was to identify predictive variables related to
      activity limitation and home destination of a large sample of first-time stroke
      patients at discharge from a rehabilitation hospital. DESIGN: A multicenter
      observational study was conducted among 1023 first-time stroke patients who were
      admitted to 18 different Italian inpatient rehabilitation centers between
      February 1999 and November 2000. Only 997 patients were considered eligible. At
      admission, sociodemographic and clinical data were considered as independent
      variables. The outcome measures evaluated the ability to become functionally
      independent (independence gain [Barthel Index score > or =18]) at discharge and
      home return. RESULTS: The study data suggest that independence gain is associated
      with an earlier rehabilitation intervention, being male, and low or absent
      cognitive deficit. Home return is associated with no indwelling bladder
      catheterization, no dysphagia, and living with a companion (roommate or family
      member) before the stroke. CONCLUSIONS: In postacute stroke rehabilitation, level
      of cognitive impairment, bladder dysfunction and dysphagia, early diagnosis and
      treatment, early rehabilitation intervention, and living status (whether the
      person was residing with a companion before the stroke) are important criteria
      for outcome measurement at the time of admission. These previous characteristics
      will most certainly provide clinicians with useful information during the acute
      phase.

PMID- 17033593
TI  - Toward benchmarks for stroke rehabilitation in Ontario, Canada.
AB  - OBJECTIVE: Canadian benchmarking data do not exist for stroke rehabilitation
      services. This study used the FIM-function-related group (FIM-FRG) classification
      system to group patients and to describe the outcomes within each group. The
      intent was to begin to develop benchmarks for persons recovering from stroke in
      Canadian rehabilitation facilities. DESIGN: 561 patients were stratified into the
      nine categories of the FIM-FRG system. Length of stay (LOS), total FIM gain,
      total FIM at discharge, and discharge location were described for each category.
      RESULTS: Mean waiting time to rehabilitation admission was 29.7 days. Mean LOS
      was 49.2 days. Mean admission and discharge total FIM ratings were 78.1 and
      103.1, respectively. FIM gain ranged from 8 to 37. Seventeen percent of patients
      were discharged to nursing homes, with rates ranging from a low of 0% (FRG 8 and
      9) to a high of 60% (FRG 2). CONCLUSIONS: For the nine FIM-FRG groups, LOS was
      considerably longer in the Canadian facility than in the United States, and total
      FIM score at discharge was higher in Canada. This is likely related to
      differences in the healthcare systems of the two countries and confirms the need
      to develop benchmarks based on Canadian data.

PMID- 17033594
TI  - Severe Dysphagia after botulinum toxin B injection to the lower limbs and lumbar
      paraspinal muscles.
AB  - We report a case of severe dysphagia in a 29-yr-old woman with cerebral palsy
      after she was injected with botulinum toxin B to her lower limbs and lumbar
      paraspinal muscles. Four days after the treatment, she developed difficulty
      swallowing, more severe for solid foods than for liquids, accompanied by dry
      mouth, blurred vision, and voice hoarseness. Fifteen days after the injection,
      with worsening of her dysphagia, she was hospitalized. A laryngoscopic evaluation
      revealed bilateral vocal cord paresis, and a modified barium swallow test
      demonstrated delayed oral initiation, upper airway penetration, and no reflexive
      cough. In the following days, she improved spontaneously and was discharged 12
      days later when she re-acquired the ability to swallow solid foods. Her symptoms
      resolved completely only 75 days after the injection. Although dysphagia is a
      common side effect of botulinum injection in the neck, to our knowledge, this is
      the first reported case of severe dysphagia after injection in a distant anatomic
      site.

PMID- 17033595
TI  - Adding challenge to performance-based tests of walking: The Walking InCHIANTI
      Toolkit (WIT).
AB  - OBJECTIVE: In this report, we provide a detailed description of and
      reproducibility data on the 14 performance-based tests of lower limb function
      included in the Walking InCHIANTI Toolkit, which were designed to mimic
      challenging situations that are encountered while walking in daily life. DESIGN:
      Five women and five men were randomly selected from each of the age strata, 65
      74, 75-84, and > or =85 yrs, among those who received a functional evaluation in
      the Greve site at the second InCHIANTI study follow-up (total n = 30). Walking
      tests were administered twice at 2-wk intervals. Analyses were aimed at assessing
      reproducibility of the Walking InCHIANTI Toolkit components and the existence of
      a learning effect. RESULTS: Performance remained stable for eight walking tests
      and slightly but significantly improved for the 25-cm narrow-path walk, 7-m usual
      pace, 7-m obstacle normal light, 7-m holding a package, and 7-m talking while
      walking tests. Test-retest reliability was in general very high, with 11 of 14
      (79%) of the intraclass correlation coefficient values >0.80 and all except one
      (7-m holding a package) >0.75. CONCLUSION: The walking tests included in the
      Walking InCHIANTI Toolkit show very good medium-term reproducibility and modest
      learning effect. Administering components of the Walking InCHIANTI Toolkit may
      help in the understanding of the effect of challenges encountered in daily life
      on walking performance.

PMID- 17033596
TI  - Thoracic endovascular repair--this is just the beginning.

PMID- 17033597
TI  - Interventional strategies for treatment of aortic dissection.
AB  - Endovascular treatment of chronic aneurysmatic diseases of the thoracic aorta has
      demonstrated encouraging peri-interventional mortality and morbidity and is
      accepted as a preferred strategy. The emerging of endovascular strategies for
      acute thoracic aortic dissection is an even more exciting new territory for
      nonsurgical interventions considering the sobering results of open surgery.
      Although it is apparent that patients at high risk for open surgery will benefit
      from endovascular strategies, the exact role of stent-graft placement remains to
      be defined at present as the community awaits solid long-term data and as devices
      and techniques continue to improve. While some indications and scenarios such as
      acute type B dissection with associated malperfusion syndrome or imminent aortic
      rupture have shown to benefit from stent-graft treatment, others are less
      settled. The current paper discusses both the established and emerging
      indications, as well as all technical aspects of this fascinating new therapeutic
      alternative. Moreover, the currently available data from small studies and
      registries are commented and analysed. Based on the available information the
      cardiovascular community is in the early phase of integrating a new rapidly
      evolving interventional concept into the care of patients with type B aortic
      dissection that so far lacked a reasonable therapeutic option other than blood
      pressure lowering medication. With the use and interpretation of current
      information the reader will understand the potential of interventional stent
      graft induced thoracic aortic repair in type B aortic dissection.

PMID- 17033598
TI  - Novel technique: staged hybrid surgical and endovascular treatment of acute Type
      A aortic dissections with aortic arch involvement.
AB  - AIM: The standard approach for treating acute Type A aortic dissections (TAD) is
      replacement of the ascending aorta utilizing hypothermic circulatory arrest
      (HCA), which is associated with significant morbidity and frequently leaves a
      residual aortic arch dissection. We describe a staged surgical and endovascular
      technique of ascending aorta replacement and simultaneous aorto-innominate artery
      bypass without HCA, followed 4 weeks later by carotid-carotid bypass and
      endovascular exclusion of the remaining arch dissection with a thoracic
      endograft. METHODS: From December 2004 to December 2005, 5 consecutive patients
      (mean age 58 +/- 6.9 years) with TADs underwent the staged procedure. All
      patients underwent replacement of the ascending aorta and aorto-innominate
      bypass. Two patients subsequently underwent the second endovascular stage. In one
      patient the aortic false lumen completely thrombosed following the first surgical
      stage and two patients are currently awaiting the endovascular stage. RESULTS:
      There were no major adverse events (death, cerebrovascular accident or
      paraplegia) following the first surgical stage. One patient suffered a transient
      minor stroke. The 2 patients who underwent the second endovascular stage showed
      no immediate adverse events. Postoperative CT scans have demonstrated that the
      false channel was excluded from the aortic arch down to the distal end of the
      endograft in the descending aorta in each case, but became patent further
      downstream. CONCLUSIONS: This procedure appears safe and feasible. It may allow
      for a more definitive treatment of TADs than the standard surgical approach. It
      can be adapted by low volume centers, surgeons untrained in aortic arch repair,
      and in high risk patients.

PMID- 17033599
TI  - Remodeling of the thoracic aorta after stent grafting of type B dissection: a
      Swedish multicenter study.
AB  - AIM: Endovascular repair of complicated type B dissections has evolved as a
      promising alternative to open repair. Previous studies have indicated that
      continued false lumen flow is a predictor of continued aortic dilatation and risk
      of rupture during follow-up. This multicenter study was conducted to analyze the
      postoperative changes of the false lumen after endografting of complicated type B
      dissections. METHODS: All patients treated with endovascular stent grafts for
      thoracic type B dissections at 5 major Vascular Centers in Sweden were identified
      through local databases. Review of charts and all available pre- and
      postoperative CT scans were performed to identify demographics, indications for
      repair as well as postoperative changes of the aorta and false lumen. RESULTS: A
      total of 129 patients treated for type B dissections between 1994 and December
      2005 were identified. Median radiological follow-up was 14 months. Fourteen
      patients died perioperatively leaving 115 patients available for analysis.
      Seventy-four of these had CT imaging of sufficient quality for morphological
      analysis. The vast majority of acute patients were treated for rupture or end
      organ ischemia whereas most chronic patients were treated for asymptomatic
      aneurysms. In 80% of patients, the false lumen thrombosed along the stent graft
      but it remained perfused distal to the stent graft fixation in 50% of patients.
      Only 5% of patients presented with aortic enlargement of the stent grafted area
      when adequate proximal sealing was achieved. The distal, uncovered aorta
      displayed expansion in 16% of patients. CONCLUSIONS: The stent grafted thoracic
      aorta after type B dissection appears to be stabilized by covering the primary
      entry site with a stent graft in the majority of both acute and chronic
      dissections. The uncovered portion of the aorta distal to the stent graft,
      however, remains at risk of continuous dilatation. Stent grafting for complicated
      type B thoracic dissections seems to be a treatment option with reasonable
      morbidity and mortality even though the incidence of severe complications is
      still significant.

PMID- 17033600
TI  - Hybrid aortic procedures for endoluminal arch replacement in thoracic aneurysms
      and type B dissections.
AB  - The aim of this study was to report our clinical experience with and review
      current literature on endoluminal aortic hybrid techniques and to evaluate
      outcome in high-risk patients treated for complex aortic arch lesions combining
      conventional supra-aortic debranching bypasses with subsequent or staged thoracic
      endovascular grafting. Of 172 patients treated with thoracic endografts for
      different thoracic aortic pathologies within the last 8 years, the mid-aortic
      arch was involved in 25, i.e. at least the left common carotid artery had to be
      overstented and revascularized to provide a proper proximal landing zone. These
      debranching bypasses were performed as a simultaneous or a staged procedure. All
      patients were at high-risk and were excluded by cardiac surgeons as ineligible
      for conventional arch repair. After partial (n=16) or complete (n=9) supra-aortic
      transposition, 4 different commercially available endografts (80% TAG, WL Gore)
      were implanted transfemorally or via iliac conduit. Deployment success was 100%
      in 25 patients after simultaneous or staged supra-aortic transposition; in 32% an
      emergency procedure was performed due to contained rupture; in 36% more than 1
      endograft system was implanted (2 in 20%, 3 in 8% und 4 in 8%). The overall
      perioperative thirty-day mortality was 5 of 25 (20%) due to interoperative
      proximal bare stent perforation (n=1), transfusion related acute lung injury
      (TRALI n=1), cardiac failure (n=1), embolic stroke (n=1) and pneumonia (n=1). The
      mean follow-up was 21 months. All endoleaks type I (n=3) were corrected with
      another endograft; the 2 endoleaks type II sealed spontaneously. The major
      adverse events were: prolonged ventilation in 5 (20%), temporary renal
      insufficiency with hemodialysis (n=2), bypass infection (n=1), without any
      complications (n=9). No cases of paraplegia were recorded. Hybrid aortic arch
      repair is technically challenging but feasible. This novel approach may be an
      alternative to standard open procedures in high-risk patients and emergency
      cases. However, the promising early results need to be confirmed by longer follow
      up and larger series.

PMID- 17033602
TI  - Laparoscopic assisted aortic surgery. A review.
AB  - We give an overview of different laparoscopic assisted techniques to perform
      aortic surgery. In a meta-analysis the paper describes the combined experience of
      two vascular surgical centers who together have performed more than 524
      laparoscopic assisted aortic procedures. Basically the following techniques can
      be used to perform a laparoscopic assisted procedure: 1) transperitoneal approach
      (the Alimi procedure); 2) hand assisted laparoscopy (the Ferrari technique); 3)
      left retrocolic laparoscopic assisted; 4) combining laparoscopic assisted and
      total laparoscopy techniques. In all cases a transperitoneal approach was chosen
      to dissect the aorta. This was either accomplished directly or using a left
      retrocolic access originally described by Dion as the apron technique. In some
      cases a hand assist device was used, which permits the surgeon to introduce the
      non dominant hand while maintaining the pneumoperitoneum. The mortality in
      abdominal aortic aneurysm (AAA) patients in either center did not exceed 1.8%.
      ICU stay, postoperative ileus and length of stay were significantly shorter
      compared to patients with a full length incision. The Pisa group showed that
      there is still a significant reduction of operating time as well as aortic cross
      clamping time beyond the learning curve of the first 30 patients. The analysis of
      the pooled data shows that even in AAA patients the laparoscopic assisted
      procedure can be performed with operating times of less than 3 h and hospital
      stays up to 4 days, which we only know from endovascular aneurysm exclusion. This
      is the first publication of hand assisted laparoscopic endoaneurysm repair
      involving a large number of patients. The operations can be performed with
      expediency and safety. We can use these laparoscopic procedures to perform even
      complex aortic operations including suprarenal aneurysms with revascularization
      of the renal and visceral arteries. An outlook of future developments including
      stapling technology is given.

PMID- 17033601
TI  - Carotid angioplasty and stenting under protection. Techniques, results and
      limitations.
AB  - A carotid stenosis is responsible for about 30% of strokes occurring. Carotid
      endarterectomy (CEA) is considered to be the gold standard treatment of a carotid
      stenosis. Carotid angioplasty and stenting (CAS) is emerging as a new alternative
      treatment for a carotid artery stenosis, but the risk of neurological
      complications and brain embolism remains the major drawback to this procedure.
      Therefore, in order to reduce the risks, we need: 1) good indications, good
      patient and lesion selection; 2) correct techniques; 3) brain protection devices
      (cerebral protection devices should be routinely used and are mandatory for any
      procedure); 4) 3 types of protection devices are available, but filters are the
      most commonly used (all protection devices have limitations and cannot prevent
      from all embolic events; however, neurological complications can be reduced by
      60%); 5) a good choice of the stent and correct implantation (all stents are not
      equivalent and have different geometrical effects); 6) pharmacological adjuncts;
      7) a good team. Recent studies have shown that CAS has superior short-term
      outcomes than CEA in high surgical risk patients, but there are enough reported
      data to conclude that CAS is also not inferior to CEA in low-risk patients. CAS
      under protection is the standard of care and is maybe becoming the gold standard
      treatment of a carotid stenosis at least in some subgroups of patients.

PMID- 17033603
TI  - Shrinkage of abdominal aortic aneurysm after successful endovascular repair:
      results from single center study.
AB  - AIM: In the literature, the behavior of the aneurysm sac after endovascular
      grafting has been the subject of significant speculation. It has been suggested
      that shrinkage of the abdominal aortic aneurysm (AAA) is different for various
      endografts. This study was undertaken to evaluate endograft-specific differences
      in aneurysm sac shrinkage and to evaluate other factors that may influence AAA
      shrinkage. METHODS: Forty patients with an AAA treated with endovascular grafts
      with a complete 18 months follow-up and complete CT angiography (CTA) follow-up
      were available for analysis. All patients with a persistent endoleak, endograft
      migration or any other reason for intervention or conversion were excluded from
      this analysis. Shrinkage was defined as a reduction in the AAA diameter of 5 mm
      or more. Chi-squared tests were used to test whether shrinkage was different for
      the kind of stent graft used (Gore Excluder vs Cook-Zenith), preexistent AAA
      diameter (<65 mm vs =or>65 mm), and AAA status (ruptured vs non-ruptured) (two
      sided; a= 0.05). RESULTS: At 18 months after treatment, shrinkage was observed in
      14 patients (52%) of the 27 patients treated with a Gore Excluder endograft and
      in 8 patients (62%) of the 13 patients treated with a Cook Zenith endograft
      (P=0.74). In 31 patients with a diameter <65 mm, shrinkage was observed in 19
      patients (61%) whereas of the 9 patients with a diameter =or>65 mm, shrinkage was
      observed in 3 patients (33%) (P=0.253). Of the 34 patients with a non-ruptured
      AAA, shrinkage was observed in 18 patients (53%) versus of the 6 patients with a
      ruptured AAA shrinkage was observed in 4 patients (66%) (P=0.673). CONCLUSIONS:
      From this study can be concluded that the influence of the endograft on shrinkage
      of the AAA sac might be less prominent than suggested in the literature.
      Furthermore, our study shows that other factors such as preexistent AAA diameter
      may influence AAA shrinkage after endovascular repair.

PMID- 17033605
TI  - Clinical outcome after composite grafting of calcified left anterior descending
      arteries.
AB  - AIM: The treatment of a severely calcified left anterior descending coronary
      artery (LAD) remains a challenge in cardiac surgery. The objective of this
      retrospective study was to assess the early clinical outcome obtained from LAD
      reconstruction, which was performed using a combination of both, saphenous vein
      and the left internal thoracic artery (LITA) as a composite graft, in order to
      achieve complete revascularization. METHODS: Between January 1998 and December
      2003, 71 patients, 13 female and 58 male, with a mean age of 67+/-9.12 years were
      retrospectively analyzed. All patients suffered from a severe 3-vessel disease
      with a diffusely calcified LAD. The design of the reconstruction consisted in a
      long arteriotomy of the LAD grafted with a matched segment of the saphenous vein
      using the plaque exclusion technique to avoid endarterectomy. The LITA was then
      anastomosed to the saphenous vein in an end-to-end configuration. With this
      design, the saphenous vein was used first as a ''patch'' reconstruction of the
      LAD and second as an elongation for the LITA. The clinical outcome was assessed
      by mailed questionnaires or by telephone interview with the responsible
      cardiologist or general practitioner. RESULTS: The follow-up was 100%, comprising
      a mean follow-up time of 17+/-11.8 months. Overall mortality was 7% (N=5/71).
      Four cardiac deaths and 1 non cardiac-related death were registered. The in
      hospital mortality was 2.8% (2/71); 2 cardiac-related deaths and one non cardiac
      related death were observed after 30 days (4.2%). Postoperative myocardial
      infarction without heart failure was seen in 4 patients (5.4%). In addition, an
      episode of transitory cerebral ischemia was observed in 1 patient (1.4%). No
      further postoperative complications occurred. At the time of evaluation, 67% of
      the patients were in functional class CCS 0 and 33% in functional class CCS I to
      II. CONCLUSIONS: Composite graft reconstruction without endarterectomy is an
      alternative treatment option for severely calcified LADs with a good early
      clinical outcome.

PMID- 17033604
TI  - The role of N-acetylcysteine in lower extremity ischemia/reperfusions.
AB  - AIM: To evaluate the efficacy of N-acetyl cysteine (NAC) in lower extremity
      ischemia/reperfusion. METHODS: A total of 23 patients who underwent surgical
      intervention due to acute femoral artery occlusion were assigned into 2 groups:
      control group (group 1, n=12); and NAC group (group 2, n=11). Patients in NAC
      group received NAC before reperfusion, and 8 and 16 h after reperfusion (3x300
      mg), while patients in control group received only NaCl 0.9% (3x100 mL).
      Catalase, malondialdehyde (MDA) and thiol concentrations were determined in
      femoral vein samples collected at 6 different time points: before reperfusion
      (t1), and 30 min (t2), 2 h (t3), 6 h (t4), 12 h (t5) and 24 h (t6) after
      reperfusion. Alveolar-arterial oxygen gradient (A-aO2) was calculated in radial
      artery blood samples simultaneously collected at the same time points. RESULTS:
      No significant differences between the two groups with regard to age (control
      group 61+/-13 and NAC group 64+/-11 years), gender (control group M/F: 7/5, NAC
      6/5) and the average time from onset of symptoms (control group 9.6+/-3.5 h, and
      NAC group 10.2+/-3.1 h) were present. Catalase enzyme activity increased with
      reperfusion in both groups and there were no differences between the two groups.
      MDA levels did not change significantly with reperfusion in NAC group, whereas
      they were significantly higher in control group at t2 and t3 compared to NAC
      group (P<0.05). Thiol concentrations decreased with reperfusion in control group,
      and in NAC group increases that started with reperfusion returned back to
      baseline levels after 24 hours. Although the A-aO2 gradient increased in both
      groups with the beginning of reperfusion, the most prominent increase occurred in
      control group (P<0.05). CONCLUSIONS: In control group, the significant increase
      in MDA levels and A-aO2 gradient in reperfusion phase were considered a sign of
      local and end organ injury. We did not observe these changes in NAC performed
      group thus showing the efficacy of NAC.

PMID- 17033606
TI  - Beating heart mitral valve replacement with retrograde coronary sinus perfusion
      technique.
AB  - AIM: The aim of this study was to assess the efficacy and applicability of on
      pump beating heart mitral valve replacement with Sorin Bicarbon prosthesis using
      retrograde coronary sinus perfusion. METHODS: The prospective study included 17
      consecutive patients who underwent mitral valve replacement with Sorin Bicarbon
      prosthesis using retrograde coronary sinus perfusion. The operative variables and
      early outcome of this procedure are presented. RESULTS: Retrograde coronary sinus
      perfusion and venting the heart from the aorta and from the pulmonary vein
      provided good visualization of the operative field and performance of the
      operations without any difficulty. Partial oxygen pressures of coronary sinus
      perfusion blood and the returning blood from the coronary ostia were 299.7+/-30.7
      and 37.6+/-6.2 mmHg respectively. Postoperative peak creatine kinase-MB and
      troponin T values were 58+/-28.5 IU/L and 1.5+/-0.4 ng/mL, respectively. No
      mortality or major complication was observed and all the patients were discharged
      from the hospital in good condition. CONCLUSIONS: On-pump beating heart mitral
      valve replacement with Sorin Bicarbon is a good surgical option, and it has the
      advantage of maintaining physiologic condition of the heart throughout the
      procedure.

PMID- 17033607
TI  - ''BioGlue'' as a possible cause of acute blocked mechanical mitral valve leaflet.
AB  - A young patient with aortic and mitral valve infective endocarditis and advanced
      destruction of the surrounding tissues underwent a complex reconstructive
      surgery, including double valve replacement, reconstruction of aortic-mitral
      continuity and ascending aorta. Intraoperative transesophageal echocardiography
      revealed a blocked mitral leaflet, which was released by valve cleaning and
      reorientation. The application of biological glue may be a key point for this
      complication.

PMID- 17033608
TI  - Perioperative optic neuropathy following off-pump coronary artery bypass
      grafting.
AB  - Visual loss from ischemic perioperative optic neuropathy (PON) rarely occurs
      during the postoperative period of patients undergoing cardiac surgery. Since the
      first description, PON has been associated with cardiopulmonary bypass (CPB),
      being some CPB-related complications and epiphenomena considered the causes of
      such terrible complication. In particular, the risk for micro-embolization during
      aortic cannulation and clamping, the CPB-related inflammatory response, the
      hemodilution and the hypothermia during CPB could be responsible of PON. However,
      some cases of PON still remain idiopathic. We report here a very rare case of PON
      following off-pump surgery in a patient with severe coronary disease and
      multiorgan comorbidities. The case reported opens the debate on the potential
      mechanisms underlying PON, other than cardiopulmonary bypass.

PMID- 17033609
TI  - Aortic root replacement in cardiac dextroversion.
AB  - Adult cardiac surgery in patients with malrotation of the heart is rare. A 60
      year-old lady, with known cardiac dextroversion, presented with dyspnoea and pre
      syncopal attacks. Echocardiographical and radiological investigation confirmed
      the dextroversion, with clockwise rotation of the heart through its longitudinal
      axis. This resulted in the right ventricular outflow tract and pulmonary artery
      being wrapped anteriorly around the aorta, with posterior displacement of the
      right atrium. The presence of a heavily calcified, bicuspid aortic valve and
      dilated ascending aorta was also demonstrated. At surgery, venous cannulation was
      established by rotating the heart anticlockwise and access to the aortic valve
      gained with a more superior oblique aortotomy. In the presence of a dilated
      ascending aorta with a calcified, bicuspid aortic valve, the aortic root was
      replaced with a valved conduit. To the authors' knowledge, this is the first
      report of an aortic root replacement in a patient with cardiac dextroversion.

PMID- 17033610
TI  - The use of cardio-pulmonary double stage venous cannula as right inflow cannula
      for bi-ventricular assist device.

PMID- 17033611
TI  - 5-year prospective results of trimodality treatment for malignant pleural
      mesothelioma.
AB  - AIM: Even though followed by a prolonged survival in highly selected patients,
      the promising results of Sugarbaker's trimodality treatment for malignant pleural
      mesothelioma (MPM) are debated and not yet uniformly replicated. The purpose of
      this study is to evaluate prospectively the reproducibility of the trimodality
      treatment results in a patient population with mesothelioma staged by the IMIG
      classification. METHODS: Fifty-four patients with MPM have been judged candidable
      to extended pleuropneumonectomy (EPP), to be followed by chemotherapy
      (paclitaxel+carboplatin) and radiotherapy (50 Gy). RESULTS: At thoracotomy, 44 of
      the 54 surgical candidates (81%) underwent EPP; 73% of the operated patients
      completed the entire adjuvant chemo-radiotherapy with no major toxicity. The 30
      day or in-hospital operative mortality rate was 4.5% (2 deaths), the major
      morbidity 36%, and the overall complication rate 50%. At 5 years the projected
      survival of the 42 surgical survivors submitted to EPP is 19%; median survival is
      20 months. The restricted group of patients with epithelial, N0-1, completely
      resected MPM (microscopic negative margins) exhibits a projected 50% 5-year
      survival. Clinical understaging has shown up to be noticeable both at the
      thoracotomy exploration and pathology examination. Most of the disease
      recurrences are loco-regional and the current insufficiency of intraoperative or
      postsurgical radicality needs improvement, along with earlier diagnosis, more
      accurate staging, and preoperative induction for the multimodality treatment of
      pleural mesothelioma to become an established curative option. CONCLUSIONS: This
      series confirms the reproducibility of the trimodality treatment for MPM,which is
      associated with prolonged survival for early-stage tumors at the cost of a not
      prohibitive treatment-related mortality rate.

PMID- 17033612
TI  - Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas
      and soft tissue sarcomas.
AB  - AIM: The control of pulmonary metastases is important for long-term survival of
      the patients with osteosarcomas and soft tissue sarcomas. METHODS: To evaluate
      the efficacy of aggressive pulmonary metastasectomy for those patients, we
      reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our
      hospital. RESULTS: The number of metastases was only the significant risk factor
      for the curability of the metastasectomy (logistic regression analysis,
      P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The
      curability was only independent prognostic factor on multivariate analysis
      (P=0.0008). CONCLUSIONS: Early detection of pulmonary metastasis, multimodal
      perioperative treatment, and design for minimizing the volume of resected lung
      tissues will enable complete and repeat resections for the achievement of long
      term survival.

PMID- 17033613
TI  - Pulmonary vein thrombosis after lower lobectomy of the left lung.
AB  - Pulmonary vein thrombosis is a known complication after lung transplantation but
      has rarely been reported after lobectomy or bilobectomy. We report the case of a
      left upper pulmonary vein thrombosis following an uneventful left lower lobectomy
      for bronchial carcinoma. Postoperative arterial blood gas values and chest
      radiographs were normal. On postoperative day 5, the patient became progressively
      dyspneic, developed hemoptysis and showed total opacification of the left lung
      without mediastinal shift on chest radiography. The patient remained dyspneic
      despite intravenous antibiotic therapy for suspected pneumonia and absence of
      obstruction at bronchoscopy. Diagnosis of left upper pulmonary vein thrombosis
      was finally made by contrast-enhanced multislice computed tomography followed by
      pulmonary angiography. Further clinical deterioration under conservative
      treatment forced us to remove the remnant left upper lobe that already showed
      gangrenous alterations. Pulmonary vein thrombosis following lobectomy or
      bilobectomy is very rare. Only 7 cases have been reported in the literature so
      far. Conservative treatment with antibiotics and anticoagulants may be successful
      but in case of clinical deterioration the affected lobe has to be resected. The
      mechanism of thrombosis remains unclear although intraoperative torsion and
      injury of vessels seem to be most likely since pulmonary vein thrombosis occurred
      in the operated hemithorax only.

PMID- 17033614
TI  - Pharmacogenetics and ethical considerations: why care?

PMID- 17033615
TI  - Candidate genes, pathways and mechanisms for alcoholism: an expanded convergent
      functional genomics approach.
AB  - We describe a comprehensive translational approach for identifying candidate
      genes for alcoholism. The approach relies on the cross-matching of animal model
      brain gene expression data with human genetic linkage data, as well as human
      tissue data and biological roles data, an approach termed convergent functional
      genomics. An analysis of three animal model paradigms, based on inbred alcohol
      preferring (iP) and alcohol-non-preferring (iNP) rats, and their response to
      treatments with alcohol, was used. A comprehensive analysis of microarray gene
      expression data from five key brain regions (frontal cortex, amygdala, caudate
      putamen, nucleus accumbens and hippocampus) was carried out. The Bayesian-like
      integration of multiple independent lines of evidence, each by itself lacking
      sufficient discriminatory power, led to the identification of high probability
      candidate genes, pathways and mechanisms for alcoholism. These data reveal that
      alcohol has pleiotropic effects on multiple systems, which may explain the
      diverse neuropsychiatric and medical pathology in alcoholism. Some of the
      pathways identified suggest avenues for pharmacotherapy of alcoholism with
      existing agents, such as angiotensin-converting enzyme (ACE) inhibitors.
      Experiments we carried out in alcohol-preferring rats with an ACE inhibitor show
      a marked modulation of alcohol intake. Other pathways are new potential targets
      for drug development. The emergent overall picture is that physical and
      physiological robustness may permit alcohol-preferring individuals to withstand
      the aversive effects of alcohol. In conjunction with a higher reactivity to its
      rewarding effects, they may able to ingest enough of this nonspecific drug for a
      strong hedonic and addictive effect to occur.

PMID- 17033616
TI  - Evaluation of ideal irrigation fluid in 'Greenlight' photoselective vapourization
      of the prostate.
AB  - Although many anecdotal opinions are available that water gives a better visual
      quality, no studies have analysed the differences in the visual quality of the
      operative field with the use of either saline or sterile water. As part of a
      prospective audit we wished to assess the effect of differing irrigant fluids on
      intraoperative visibility during Greenlight photoselective vapourization of
      prostate (PVP). Twenty-nine consecutive patients with prostates less than 100
      cm(3) who underwent PVP were studied. The irrigation fluid used was randomly
      connected on a bag-by-bag basis, with the surgeon blinded to the bag's contents.
      Towards the end of each bag the surgeon gave a score to the quality of vision.
      All surgeons were familiarized with the vision scoring system in advance. The
      scores were analysed in two ways. The mean scores for water and saline were
      compared. In addition, a mean score for each fluid in each patient where both
      fluids were used (n=24) was separately calculated and the means for each fluid
      compared. One hundred and twenty-four bags of fluid in 29 operative cases were
      analysed. The mean overall vision scores were 3.94% for saline and 4.01% for
      water (P=0.62). The paired data were analysed using the Student's t-test and
      there was no statistically significant difference (P=0.34). We showed no
      significant difference in visual quality between water and saline during PVP.
      Although fluid absorption is almost unknown with PVP, there seems to be no
      justification for using water irrigation if saline is available, particularly
      with a theoretical risk of absorption.

PMID- 17033617
TI  - Diabetes and the risk of prostate cancer: the role of diabetes treatment and
      complications.
AB  - Epidemiologic evidence suggests diabetic men have a slightly lower prostate
      cancer risk than non-diabetic men. We examined this association in a prospective
      cohort study of 35 239 men, 50-76 years old, in Washington State who completed a
      baseline questionnaire between 2000 and 2002. Incident prostate cancers as of 31
      December 2004 were identified through the SEER registry. Diabetic men had a
      slightly lower risk of prostate cancer than non-diabetic men (hazard ratio (HR)
      0.83, 95% confidence interval (CI) 0.64-1.07). Insulin users overall and insulin
      users with diabetic complications had decreased risks, compared to non-diabetic
      men (HR 0.49, 95% CI 0.26-0.92) and (HR 0.36, 95% CI 0.15-0.87), respectively.
      Oral medication use for diabetes was not associated with prostate cancer. Insulin
      is likely a marker of severity of diabetes. Future studies of this association
      should consider diabetes type, treatment, severity, complications and biomarkers.

PMID- 17033618
TI  - Salt wasting, hypotension, polydipsia, and hyponatremia and the level of spinal
      cord injury.
AB  - STUDY DESIGN: Case control. OBJECTIVE: To test the reported correlation of
      hypotension, polydipsia, and hyponatremia with higher levels of spinal cord
      injury (SCI). SETTING: A Veterans Administration Hospital, USA. METHODS: The
      records of men who were paralyzed owing to trauma at any spinal cord level with
      motor complete lesions (ASIA A or B) and who received an annual physical and
      laboratory examination were reviewed for age, duration of paralysis, level of
      paralysis, blood pressure (BP), serum sodium, and 24 h urinary volume,
      creatinine, and sodium. Creatinine clearance and fractional excretion of sodium
      (FcNa) were calculated. Spearman rank-order correlations (r (s)) were carried
      out. RESULTS: Patients were aged 25 to 88 years, median 56 years, paralyzed 2-61
      years, median 26 years, with levels of paralysis ranging from C2 to L4, median
      T4, n=111. From lower to higher levels of paralysis FcNa increased (0.4-7.3%),
      mean BP diminished (132-66 mmHg), urine volume increased (600-5400 ml), and serum
      sodium was reduced (148-129 mEq/l) - r (s)=0.29, 0.49, -0.22, and 0.23,
      respectively. Increasing 24 h urinary volumes correlated with lower serum sodium
      concentrations but higher creatinine clearance, r (s)=-0.28, 0.24. Increasing 24
      h urinary sodium improved creatinine clearance, r (s)=0.37. P-values ranged from
      <0.05 to <0.001. CONCLUSION: Higher levels of SCI correlate with reduced sodium
      conservation, hypotension, polydipsia, and hyponatremia. Greater water intake
      raises creatinine clearance but lowers serum sodium. Greater salt intake
      increases creatinine clearance.

PMID- 17033619
TI  - Spinal cord injury influences psychogenic as well as physical components of
      female sexual ability.
AB  - STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Elicit specific information
      about sexual function from women with spinal cord injuries (SCI). SETTING: World
      wide web. METHODS: Individuals 18 years or older living with SCI obtained a pass
      code to enter a secure website and then answered survey questions. RESULTS:
      Bladder and/or bowel incontinence during sexual activity and/or sexual
      intercourse were significant concerns and prevented some women from seeking
      sexual activity. Autonomic dysreflexia (AD) during sexual activity was
      interpreted negatively by many and was found to interfere with sexual activity.
      Most subjects reported difficulty becoming psychologically aroused as well as
      physically aroused, which were both correlated with feeling that their SCI had
      altered their sexual sense of self. An inverse relationship existed between
      developing new areas of arousal above the level of lesion and not having
      sensation or movement below the lesion. The most commonly reported sexual
      stimulation leading to the best arousal involved stimulation of the head/neck and
      torso areas. The majority of subjects reported having experienced intercourse
      postinjury. Most participants reported difficulty with positioning during
      foreplay and intercourse, vaginal lubrication, and spasticity during intercourse.
      Almost half reported experiencing orgasm postinjury and this was positively
      associated with the presence of genital sensation. CONCLUSION: SCI significantly
      impairs psychological and physical aspects of female sexual arousal. In addition,
      bladder and bowel incontinence as well as AD negatively impact sexual activity
      and intercourse.

PMID- 17033620
TI  - The impact of spinal cord injury on sexual function: concerns of the general
      population.
AB  - STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Obtain information from the
      spinal cord injured (SCI) population regarding sexual dysfunctions, with the aim
      of developing new basic science and clinical research and eventual therapies
      targeting these issues. SETTING: Worldwide web. METHODS: Individuals 18 years or
      older living with SCI. Participants obtained a pass-code to enter a secure
      website and answered survey questions. A total of 286 subjects completed the
      survey. RESULTS: The majority of participants stated that their SCI altered their
      sexual sense of self and that improving their sexual function would improve their
      quality of life (QoL). The primary reason for pursuing sexual activity was for
      intimacy need, not fertility. Bladder and bowel concerns during sexual activity
      were not strong enough to deter the majority of the population from engaging in
      sexual activity. However, in the subset of individuals concerned about bladder
      and/or bowel incontinence during sexual activity, this was a highly significant
      issue. In addition, the occurrence of autonomic dysreflexia (AD) during typical
      bladder or bowel care was a significant variable predicting the occurrence and
      distress of AD during sexual activity. CONCLUSION: Sexual function and its
      resultant impact on QoL is a major issue to an overwhelming majority of people
      living with SCI. This certainly constitutes the need for expanding research in
      multiple aspects to develop future therapeutic interventions for sexual health
      and SCI.

PMID- 17033621
TI  - Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes
      in mineral metabolism.
AB  - The osteocyte, a terminally differentiated cell comprising 90%-95% of all bone
      cells, may have multiple functions, including acting as a mechanosensor in bone
      (re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in
      osteocytes and, when deleted in mice, results in a hypomineralized bone
      phenotype. We investigated the potential for this gene not only to direct
      skeletal mineralization but also to regulate phosphate (P(i)) homeostasis. Both
      Dmp1-null mice and individuals with a newly identified disorder, autosomal
      recessive hypophosphatemic rickets, manifest rickets and osteomalacia with
      isolated renal phosphate-wasting associated with elevated fibroblast growth
      factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that
      autosomal recessive hypophosphatemic rickets family carried a mutation affecting
      the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the
      highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice
      demonstrated that absence of DMP1 results in defective osteocyte maturation and
      increased FGF23 expression, leading to pathological changes in bone
      mineralization. Our findings suggest a bone-renal axis that is central to guiding
      proper mineral metabolism.

PMID- 17033622
TI  - Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast
      cancer susceptibility alleles.
AB  - We identified constitutional truncating mutations of the BRCA1-interacting
      helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2
      mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we
      estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95%
      confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were
      recently shown to cause Fanconi anemia complementation group J. Thus,
      inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause
      Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer
      in monoallelic carriers.

PMID- 17033623
TI  - Nuclear organization of active and inactive chromatin domains uncovered by
      chromosome conformation capture-on-chip (4C).
AB  - The spatial organization of DNA in the cell nucleus is an emerging key
      contributor to genomic function. We developed 4C technology (chromosome
      conformation capture (3C)-on-chip), which allows for an unbiased genome-wide
      search for DNA loci that contact a given locus in the nuclear space. We
      demonstrate here that active and inactive genes are engaged in many long-range
      intrachromosomal interactions and can also form interchromosomal contacts. The
      active beta-globin locus in fetal liver preferentially contacts transcribed, but
      not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the
      inactive locus in fetal brain contacts different transcriptionally silent loci. A
      housekeeping gene in a gene-dense region on chromosome 8 forms long-range
      contacts predominantly with other active gene clusters, both in cis and in trans,
      and many of these intra- and interchromosomal interactions are conserved between
      the tissues analyzed. Our data demonstrate that chromosomes fold into areas of
      active chromatin and areas of inactive chromatin and establish 4C technology as a
      powerful tool to study nuclear architecture.

PMID- 17033624
TI  - Circular chromosome conformation capture (4C) uncovers extensive networks of
      epigenetically regulated intra- and interchromosomal interactions.
AB  - Accumulating evidence converges on the possibility that chromosomes interact with
      each other to regulate transcription in trans. To systematically explore the
      epigenetic dimension of such interactions, we devised a strategy termed circular
      chromosome conformation capture (4C). This approach involves a circularization
      step that enables high-throughput screening of physical interactions between
      chromosomes without a preconceived idea of the interacting partners. Here we
      identify 114 unique sequences from all autosomes, several of which interact
      primarily with the maternally inherited H19 imprinting control region. Imprinted
      domains were strongly overrepresented in the library of 4C sequences, further
      highlighting the epigenetic nature of these interactions. Moreover, we found that
      the direct interaction between differentially methylated regions was linked to
      epigenetic regulation of transcription in trans. Finally, the patterns of
      interactions specific to the maternal H19 imprinting control region underwent
      reprogramming during in vitro maturation of embryonic stem cells. These
      observations shed new light on development, cancer epigenetics and the evolution
      of imprinting.

PMID- 17033625
TI  - DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix
      protein in the regulation of phosphate homeostasis.
AB  - Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an
      autosomal recessive form (designated ARHP) to chromosome 4q21 and identified
      homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non
      collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact
      plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of
      four affected individuals, providing a possible explanation for the phosphaturia
      and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may
      regulate FGF23 expression.

PMID- 17033626
TI  - Speciation genetics: evolving approaches.
AB  - Much progress has been made in the past two decades in understanding Darwin's
      mystery of the origins of species. Applying genomic techniques to the analysis of
      laboratory crosses and natural populations has helped to determine the genetic
      basis of barriers to gene flow which create new species. Although new
      methodologies have not changed the prevailing hypotheses about how species form,
      they have accelerated the pace of data collection. By facilitating the
      compilation of case studies, advances in genetic techniques will help to provide
      answers to the next generation of questions concerning the relative frequency and
      importance of different processes that cause speciation.

PMID- 17033627
TI  - The genetic dissection of essential hypertension.
AB  - QTL mapping in humans and rats has identified hundreds of blood-pressure-related
      phenotypes and genomic regions; the next daunting task is gene identification and
      validation. The development of novel rat model systems that mimic many elements
      of the human disease, coupled with advances in the genomic and informatic
      infrastructure for rats, promise to revolutionize the hunt for genes that
      determine susceptibility to hypertension. Furthermore, methods are evolving that
      should enable the identification of candidate genes in human populations.
      Together with the computational reconstruction of regulatory networks, these
      methods provide opportunities to significantly advance our understanding of the
      underlying aetiology of hypertension.

PMID- 17033628
TI  - Brain morphological changes associated with exposure to HSV1 in first-episode
      schizophrenia.
AB  - Infectious agents have been proposed as one of the risk factors for
      schizophrenia. However, the data on the association of infectious agents with in
      vivo brain changes are scant. We evaluated the association of serological
      evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain
      structural variations among first-episode antipsychotic-naive
      schizophrenia/schizoaffective disorder patients and control subjects. We assayed
      HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44
      healthy subjects and obtained structural magnetic resonance imaging scans from
      the same individuals. There were proportionately more patients with elevated HSV1
      antibody ratios than healthy comparison subjects (chi2=3.98, 1 df, P=0.046) and
      patients had significantly higher HSV1 IgG antibody ratios compared with healthy
      subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1
      serological status interaction followed by within- and between-group comparison
      across the serological status. We observed a diagnosis by HSV1 serological status
      interaction and a significant main effect of HSV1 serological status in the
      prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in
      Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate
      cortex) compared with patients without serological evidence of exposure to HSV1.
      HSV1-associated differences in brain structure were not detected among healthy
      subjects. These findings suggest that HSV1 exposure in schizophrenia is
      associated with specific regional gray matter differences that may not be
      attributable to medications, illness chronicity or comorbid substance use. This
      study provides suggestive evidence for a link between HSV1 exposure and some of
      the cerebral morphological changes often reported in schizophrenia.

PMID- 17033629
TI  - Decreased circulating CD34+ stem cells in early Alzheimer's disease: Evidence for
      a deficient hematopoietic brain support?
AB  - Hematopoietic stem cells contribute to mammalian brain tissue regeneration by
      transdifferentiation processes. We found decreased counts of circulating CD34+
      cells in early Alzheimer's dementia (AD; P = 0.01), which significantly
      correlated with age (r = -0.661; P = 0.001), cerebrospinal fluid beta-amyloid
      (Abeta)1-42 (r = -0.467; P = 0.025) and most pronounced the Abeta42/40 ratio (r =
      -0.688; P = 0.005). Our data suggest a deficient regenerative hematopoietic
      support for the central nervous system in early AD.

PMID- 17033630
TI  - Serotonin transporter gene variation impacts innate fear processing: Acoustic
      startle response and emotional startle.
AB  - Anxiety-related behaviors are closely linked to neural circuits relaying fear
      specific information to the amygdala. Many of these circuits, like those
      underlying processing of innate fear, are remarkably well understood. Recent
      imaging studies have contributed to this knowledge by discriminating more
      detailed corticoamygdalar associations mediating processing fear and anxiety.
      However, little is known about the underlying molecular mechanisms. We used the
      acoustic startle paradigm to investigate the impact of molecular genetic
      variation of serotonergic function on the acoustic startle response and its fear
      potentiation. Startle magnitudes to noise bursts as measured with the eye blink
      response were recorded in 66 healthy volunteers under four conditions: presenting
      unpleasant and pleasant affective pictures as well as neutral pictures, and
      presenting the startle stimulus without additional stimuli as a baseline.
      Subjects were genotyped for functional polymorphism in the transcriptional
      control region of the serotonin transporter gene (5-hydroxytryptamine transporter
      gene-linked region: 5-HTTLPR). Analyses of variance revealed a significant effect
      of 5-HTTLPR on overall startle responses across conditions. Carriers of the short
      (s) allele exhibited stronger startle responses than l/l homozygotes. However, we
      could not confirm our hypothesis of enhanced fear potentiation of the startle in
      s allele carriers. In conclusion, the results provide first evidence that the
      startle response is sensitive to genetic variation in the serotonin pathway.
      Despite some issues remaining to be resolved, the startle paradigm may provide a
      valuable endophenotype of fear processing and underlying serotonergic influences.

PMID- 17033631
TI  - Improvement of cognitive functions in chronic schizophrenic patients by
      recombinant human erythropoietin.
AB  - Schizophrenia is increasingly recognized as a neurodevelopmental disease with an
      additional degenerative component, comprising cognitive decline and loss of
      cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on
      strategy, recombinant human erythropoietin (rhEPO) in addition to stable
      antipsychotic medication, may be able to improve cognitive function even in
      chronic schizophrenic patients. Therefore, we designed a double-blind, placebo
      controlled, randomized, multicenter, proof-of-principle (phase II) study. This
      study had a total duration of 2 years and an individual duration of 12 weeks with
      an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with
      defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS)), stable medication and
      disease state, were treated for 3 months with a weekly short (15 min) intravenous
      infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was
      schizophrenia-relevant cognitive function at week 12. The neuropsychological test
      set (RBANS subtests delayed memory, language-semantic fluency, attention and
      Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2
      days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both
      placebo and rhEPO patients improved in all evaluated categories. Patients
      receiving rhEPO showed a significant improvement over placebo patients in
      schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no
      effects on psychopathology or social functioning. Also, a significant decline in
      serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that
      rhEPO is the first compound to exert a selective and lasting beneficial effect on
      cognition should encourage new treatment strategies for schizophrenia.

PMID- 17033632
TI  - Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes
      for diagnosis and brain developmental trajectories.
AB  - Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of
      12, is a rare and malignant form of the illness, which may have more salient
      genetic influence. Since the initial report of association between neuregulin 1
      (NRG1) and schizophrenia in 2002, numerous independent replications have been
      reported. In the current study, we genotyped 56 markers (54 single-nucleotide
      polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS
      patients and their parents. We used family-based association analysis for both
      diagnostic (extended transmission disequilibrium test) and quantitative
      phenotypes (quantitative transmission disequilibrium test) and mixed-model
      regression. Most subjects had prospective anatomic brain magnetic resonance
      imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165
      healthy controls in the MRI study to examine genetic risk effects on normal brain
      development. Individual markers showed overtransmission of alleles to affecteds
      (P=0.009-0.05). Further, several novel four-marker haplotypes demonstrated
      significant transmission distortion. There was no evidence of epistasis with SNPs
      in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid
      social functioning. Further, possession of the risk allele was associated with
      different trajectories of change in lobar volumes. In the COS group, risk allele
      carriers had greater total gray and white matter volume in childhood and a
      steeper rate of subsequent decline in volume into adolescence. By contrast, in
      healthy children, possession of the risk allele was associated with different
      trajectories in gray matter only and was confined to frontotemporal regions,
      reflecting epistatic or other illness-specific effects mediating NRG1 influence
      on brain development in COS. This replication further documents the role of NRG1
      in the abnormal brain development in schizophrenia. This is the first
      demonstration of a disease-specific pattern of gene action in schizophrenia.

PMID- 17033633
TI  - Further evidence that the KIAA0319 gene confers susceptibility to developmental
      dyslexia.
AB  - The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to
      developmental dyslexia (DD). Two candidate genes within this region have recently
      been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have
      shown association with DD in a US and a German sample. However, when we genotyped
      these specific variants in two large, independent UK samples, we obtained only
      weak, inconsistent evidence for their involvement in DD. Having previously found
      evidence that variation in the KIAA0319 gene confers susceptibility to DD, we
      sought to refine this genetic association by genotyping 36 additional SNPs in the
      gene. Nine SNPs, predominantly clustered around the first exon, showed the most
      significant association with DD in one or both UK samples, including rs3212236 in
      the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We
      have thus refined the region of association with developmental dyslexia to
      putative regulatory sequences around the first exon of the KIAA0319 gene,
      supporting the presence of functional mutations that could affect gene
      expression. Our data also suggests a possible interaction between KIAA0319 and
      DCDC2, which requires further testing.

PMID- 17033634
TI  - Plexin B3 is genetically associated with verbal performance and white matter
      volume in human brain.
AB  - The presence of genetic influences on cognitive performance and brain volume is
      well established. However, specific genetic determinants of the variance of these
      quantitative traits are not yet known. Plexins act as receptors for semaphorins
      and are implicated in axon guidance, which is a key process in brain development.
      We have previously shown that plexin B3 is a highly potent stimulator of neurite
      outgrowth, which makes its gene PLXNB3 an intriguing candidate gene for traits
      related to human brain development and cerebral connectivity. We identified
      several polymorphisms in PLXNB3 predicting changes of amino acids (V598I, E1156D
      and V1596E) conserved at the corresponding positions of the orthologs in mouse
      and chimpanzee. PLXNB3 was genotyped in 303 healthy volunteers and 42 male
      patients with schizophrenia. Cognitive performance was measured with the
      vocabulary test (Wortschatztest (WST)), a method to estimate roughly general
      intelligence (g). Brain morphology was characterized by magnetic resonance
      imaging. Compared to subjects not carrying the modern, human-specific haplotype
      A, carriers of A scored higher in vocabulary test (WST) irrespective of diagnosis
      (P=0.0004). This effect could be observed in three independent groups (healthy
      males: P=0.048; schizophrenic males: P=0.034 and healthy females: P=0.037).
      Additionally, the haplotype A was associated with increased volume of brain white
      matter that in turn correlated with performance in the vocabulary test. These
      findings suggest that plexin B3 may influence cognitive performance, and the
      development of white matter in vivo in a way similar to its known stimulating
      effect on neurite outgrowth in vitro. These novel observations warrant further
      replication in independent samples.

PMID- 17033636
TI  - The genetics of autistic disorders and its clinical relevance: a review of the
      literature.
AB  - Twin and family studies in autistic disorders (AD) have elucidated a high
      heritability of the narrow and broad phenotype of AD. In this review on the
      genetics of AD, we will initially delineate the phenotype of AD and discuss
      aspects of differential diagnosis, which are particularly relevant with regard to
      the genetics of autism. Cytogenetic and molecular genetic studies will be
      presented in detail, and the possibly involved aetiopathological pathways will be
      described. Implications of the different genetic findings for genetic counselling
      will be mentioned.

PMID- 17033635
TI  - Region-specific transcriptional changes following the three antidepressant
      treatments electro convulsive therapy, sleep deprivation and fluoxetine.
AB  - The significant proportion of depressed patients that are resistant to
      monoaminergic drug therapy and the slow onset of therapeutic effects of the
      selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake
      inhibitors (SNRIs) are two major reasons for the sustained search for new
      antidepressants. In an attempt to identify common underlying mechanisms for fast-
      and slow-acting antidepressant modalities, we have examined the transcriptional
      changes in seven different brain regions of the rat brain induced by three
      clinically effective antidepressant treatments: electro convulsive therapy (ECT),
      sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset
      antidepressant. Each of these antidepressant treatments was applied with the same
      regimen known to have clinical efficacy: 2 days of ECT (four sessions per day),
      24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional
      changes were evaluated on RNA extracted from seven different brain regions using
      the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated
      using in situ hybridization or autoradiography for selected genes. The major
      findings of the study are: 1. The transcriptional changes induced by SD, ECT and
      SSRI display a regionally specific distribution distinct to each treatment. 2.
      The fast-onset, short-lived antidepressant treatments ECT and SD evoked
      transcriptional changes primarily in the catecholaminergic system, whereas the
      slow-onset antidepressant FLX treatment evoked transcriptional changes in the
      serotonergic system. 3. ECT and SD affect in a similar manner the same brain
      regions, primarily the locus coeruleus, whereas the effects of FLX were primarily
      in the dorsal raphe and hypothalamus, suggesting that both different regions and
      pathways account for fast onset but short lasting effects as compared to slow
      onset but long-lasting effects. However, the similarity between effects of ECT
      and SD is somewhat confounded by the fact that the two treatments appear to
      regulate a number of transcripts in an opposite manner. 4. Multiple transcripts
      (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoid-regulated
      kinase (Sgk1)), whose level was reported to be affected by antidepressants or
      behavioral manipulations, were also found to be regulated by the treatments used
      in the present study. Several novel findings of transcriptional regulation upon
      one, two or all three treatments were made, for the latter we highlight homer,
      erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1),
      glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled
      receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5.
      Transcripts encoding proteins involved in synaptic plasticity in the hippocampus
      were strongly affected by ECT and SD, but not by FLX. The novel transcripts,
      concomitantly regulated by several antidepressant treatments, may represent novel
      targets for fast onset, long-duration antidepressants.

PMID- 17033637
TI  - Why silence is not an option.
AB  - GM products will continue to be marginalized in Europe as long as industry
      remains silent.

PMID- 17033638
TI  - Partnering with a difference.
AB  - This month marks the inaugural EuroBiO meeting, a new type of biotech partnering
      event.

PMID- 17033639
TI  - Parallel universes?
AB  - An EU Commissioner has a meeting of minds with an antibiotech agitator.

PMID- 17033640
TI  - Genentech raises stakes on PARP inhibitors.

PMID- 17033641
TI  - Polyclonal antibodies step out of the shadows.

PMID- 17033642
TI  - Poor enforcement could jeopardize China's drug innovation policy.

PMID- 17033643
TI  - Brazil next biotech trailblazer in Latin America?

PMID- 17033645
TI  - Profile. Michael Fernandez.

PMID- 17033646
TI  - Biotech patenting upturn.

PMID- 17033647
TI  - Turning plants into protein factories.

PMID- 17033648
TI  - Reactions to Eprex's adverse reactions.

PMID- 17033649
TI  - Potential impact and cost-effectiveness of Golden Rice.

PMID- 17033651
TI  - The imitation game--a computational chemical approach to recognizing life.

PMID- 17033652
TI  - Biotech buybacks--good or bad?

PMID- 17033654
TI  - The emerging nanomedicine landscape.

PMID- 17033655
TI  - Biotech patents and the inequitable conduct doctrine.

PMID- 17033656
TI  - Recent patent applications in protein purification.

PMID- 17033657
TI  - Putting proteins on the map.

PMID- 17033658
TI  - Complementary therapies for inflammation.

PMID- 17033659
TI  - Automated phosphorylation site mapping.

PMID- 17033660
TI  - Deciphering bioplastic production.

PMID- 17033661
TI  - Wastewater genomics.

PMID- 17033662
TI  - A sugar switch for anti-inflammatory antibodies.

PMID- 17033664
TI  - Deviant effects in molecular reaction pathways.
AB  - In biological networks, any manifestations of behaviors substantially 'deviant'
      from the predictions of continuous-deterministic classical chemical kinetics
      (CCK) are typically ascribed to systems with complex dynamics and/or a small
      number of molecules. Here we show that in certain cases such restrictions are not
      obligatory for CCK to be largely incorrect. By systematically identifying
      properties that may cause significant divergences between CCK and the more
      accurate discrete-stochastic chemical master equation (CME) system descriptions,
      we comprehensively characterize potential CCK failure patterns in biological
      settings, including consequences of the assertion that CCK is closer to the
      'mode' rather than the 'average' of stochastic reaction dynamics, as generally
      perceived. We demonstrate that mechanisms underlying such nonclassical effects
      can be very simple, are common in cellular networks and result in often
      unintuitive system behaviors. This highlights the importance of deviant effects
      in biotechnologically or biomedically relevant applications, and suggests some
      approaches to diagnosing them in situ.

PMID- 17033665
TI  - Post-translational modifications in the context of therapeutic proteins.
AB  - The majority of protein-based biopharmaceuticals approved or in clinical trials
      bear some form of post-translational modification (PTM), which can profoundly
      affect protein properties relevant to their therapeutic application. Whereas
      glycosylation represents the most common modification, additional PTMs, including
      carboxylation, hydroxylation, sulfation and amidation, are characteristic of some
      products. The relationship between structure and function is understood for many
      PTMs but remains incomplete for others, particularly in the case of complex PTMs,
      such as glycosylation. A better understanding of such structural-functional
      relationships will facilitate the development of second-generation products
      displaying a PTM profile engineered to optimize therapeutic usefulness.

PMID- 17033669
TI  - The hardest hire: today's chief medical officer.

PMID- 17033678
TI  - Indoor ultrafine particle exposures and home heating systems: a cross-sectional
      survey of Canadian homes during the winter months.
AB  - Exposure to airborne particulate matter has a negative effect on respiratory
      health in both children and adults. Ultrafine particle (UFP) exposures are of
      particular concern owing to their enhanced ability to cause oxidative stress and
      inflammation in the lungs. In this investigation, our objective was to examine
      the contribution of home heating systems (electric baseboard heaters, wood
      stoves, forced-air oil/natural gas furnace) to indoor UFP exposures. We conducted
      a cross-sectional survey in 36 homes in the cities of Montreal, Quebec, and
      Pembroke, Ontario. Real-time measures of indoor UFP concentrations were collected
      in each home for approximately 14 h, and an outdoor UFP measurement was collected
      outside each home before indoor sampling. A home-characteristic questionnaire was
      also administered, and air exchange rates were estimated using carbon dioxide as
      a tracer gas. Average UFP exposures of 21,594 cm(-3) (95% confidence interval
      (CI): 14,014, 29,174) and 6660 cm(-3) (95% CI: 4339, 8982) were observed for the
      evening (1600-2400) and overnight (2400-0800) hours, respectively. In an
      unadjusted comparison, overnight baseline UFP exposures were significantly
      greater in homes with electric baseboard heaters as compared to homes using
      forced-air oil or natural gas furnaces, and homes using wood stoves had
      significantly greater overnight baseline UFP exposures than homes using forced
      air natural gas furnaces. However, in multivariate models, electric oven use
      (beta=12,253 cm(-3), 95% CI: 3524, 20,982), indoor relative humidity (beta=1136
      cm(-3) %, 95% CI: 372, 1899), and indoor smoking (beta=18,192 cm(-3), 95% CI:
      2073, 34,311) were the only significant determinants of mean indoor UFP exposure,
      whereas air exchange rate (beta=4351 cm(-3) h(-1), 95% CI: 1507, 7195) and each
      10,000 cm(-3) increase in outdoor UFPs (beta=811 cm(-3), 95% CI: 244,1377) were
      the only significant determinants of overnight baseline UFP exposures. In
      general, our findings suggest that home heating systems are not important
      determinants of indoor UFP exposures.

PMID- 17033679
TI  - On ecological fallacy, assessment errors stemming from misguided variable
      selection, and the effect of aggregation on the outcome of epidemiological study.
AB  - In social and environmental sciences, ecological fallacy is an incorrect
      assumption about an individual based on aggregate data for a group. In the
      present study, the validity of this assumption was tested using both individual
      estimates of exposure to air pollution and aggregate data for 1,492
      schoolchildren living in the in vicinity of a major coal-fired power station in
      the Hadera region of Israel. In 1996 and 1999, the children underwent subsequent
      pulmonary function tests (PFT), and their parents completed a detailed
      questionnaire on their health status and housing conditions. The association
      between children's PFT results and their exposure to air pollution was
      investigated in two phases. During the first phase, PFT averages were compared
      with average levels of air pollution detected in townships, and small census
      areas in which the children reside. During the second phase, individual pollution
      estimates were compared with individual PFT results, and pattern detection
      techniques (Getis-Ord statistic) were used to investigate the spatial data
      structure. While different levels of areal data aggregation changed the results
      only marginally, the choice of indices measuring the children's PFT performance
      had a significant influence on the outcome of the analysis. As argued,
      differences between individual-level and group-level effects of exposure (i.e.,
      ecological or cross-level bias) are not necessary outcomes of data aggregation,
      and that seemingly unexpected results may often stem from a misguided selection
      of variables chosen to measure health effects. The implications of the results of
      the analysis for epidemiological studies are discussed, and recommendations for
      public health policy are formulated.

PMID- 17033680
TI  - Relative moldiness index as predictor of childhood respiratory illness.
AB  - The results of a traditional visual mold inspection were compared to a mold
      evaluation based on the Relative Moldiness Index (RMI). The RMI is calculated
      from mold-specific quantitative PCR (MSQPCR) measurements of the concentration of
      36 species of molds in floor dust samples. These two prospective mold evaluations
      were used to classify the mold condition in 271 homes of infants. Later, the
      development of respiratory illness was measured in the infants living in these
      homes and the predictive value of each classification system was evaluated. The
      binary classification of homes as either moldy or non-moldy by on-site visual
      home inspection was not predictive of the development of respiratory illness
      (wheeze and/or rhinitis) (P=0.27). Conversely, a method developed and validated
      in this paper, using the RMI index fit to a logistic function, can be used to
      predict the occurrence of illness in homes and allows stake-holders the choice
      among various levels of risk.

PMID- 17033681
TI  - Factors predicting organochlorine pesticide levels in pregnant Latina women
      living in a United States agricultural area.
AB  - Organochlorine (OC) pesticide use was restricted starting in the 1970s in
      developed countries and the 1980s and 1990s in developing countries. Current
      exposure to OC pesticides - dichlorodiphenyltrichloroethane (DDT), lindane (99%
      pure gamma-hexachlorocyclohexane (gamma-HCH)), hexachlorobenzene (HCB) - occurs
      on a limited basis. We measured para, para' (p,p')-DDE, p,p'-DDT, ortho, para'
      (o,p')-DDT, HCB, beta (beta)-HCH (the most persistent isomer of technical-grade
      HCH) and gamma-HCH in serum from 426 low-income pregnant Latina women living in
      an agricultural community in California. Detection frequencies were 94% to 100%.
      Median levels (ng/g lipid) of p,p'-DDE (1,052), p,p'-DDT (13), beta-HCH (37) and
      HCB (65) were significantly higher than United States population levels.
      Multivariate analyses of p,p'-DDE, p,p'-DDT, o,p'-DDT, beta-HCH and HCB indicate
      that time spent living outside the United States and birthplace in an area of
      Mexico with recent use of OC pesticides were significant predictors of exposure.
      Time spent living in the United States was associated with increased serum levels
      of p,p'-DDE and beta-HCH, but the increase for each year lived in the United
      States was lower than for each year lived outside the United States. There was no
      difference between the increase of HCB levels over time spent in or outside the
      United States, suggesting current and thus preventable exposure routes. However,
      we observed no associations between serum levels of any OC compound and current
      intake of saturated fat or agricultural take-home exposure risk factors.
      Lactation history and recent weight gain were negatively associated with serum
      levels of some, but not all OC compounds studied. Smoking history was borderline
      associated with elevated HCB levels. We observed no significant associations with
      body mass index. Although the weight of evidence from this study indicates that
      most exposure occurred before moving to the United States, the results for HCB
      indicate the possibility of ongoing exposure in this country.

PMID- 17033682
TI  - Macular degeneration: recent advances and therapeutic opportunities.
AB  - The central retina mediates high acuity vision, and its progressive dysfunction
      due to macular degeneration is the leading cause of visual disability among
      adults in industrialized societies. Here, we summarize recent progress in
      understanding the pathophysiology of macular degeneration and the implications of
      this new knowledge for treatment and prevention. The past decade has witnessed
      remarkable advances in this field, including the development of new, non-invasive
      retinal imaging technologies, the development of animal models for macular
      disease, and the isolation of many of the genes responsible for both early- and
      late-onset macular diseases. These advances have set the stage for the
      development of effective mechanism-based therapies.

PMID- 17033683
TI  - Patterns of neural stem and progenitor cell division may underlie evolutionary
      cortical expansion.
AB  - The dramatic evolutionary expansion of the cerebral cortex of Homo sapiens
      underlies our unique higher cortical functions, and therefore bears on the
      ultimate issue of what makes us human. Recent insights into developmental events
      during early proliferative stages of cortical development indicate how neural
      stem and progenitor cells might interact to produce cortical expansion during
      development, and could shed light on evolutionary changes in cortical structure.

PMID- 17033684
TI  - Association analysis of the ACTN3 R577X polymorphism and complex quantitative
      body composition and performance phenotypes in adolescent Greeks.
AB  - The functional allele (577R) of ACTN3, which encodes human alpha-actinin-3, has
      been reported to be associated with elite athletic status and with response to
      resistance training, while the nonfunctional allele (577X) has been proposed as a
      candidate metabolically thrifty allele. In a study of 992 adolescent Greeks, we
      show that there is a significant association (P=0.003) between the ACTN3 R577X
      polymorphism and 40 m sprint time in males that accounts for 2.3% of phenotypic
      variance, with the 577R allele contributing to faster times in an additive
      manner. The R577X polymorphism is not associated with other power phenotypes
      related to 40 m sprint, nor with an endurance phenotype. Furthermore, the
      polymorphism is not associated with obesity-related phenotypes in our population,
      suggesting that the 577X allele is not a thrifty allele, and thus the persistence
      of this null allele must be explained in other terms.

PMID- 17033685
TI  - Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box
      binding protein gene: an evolutionary approach.
AB  - The variability and mutational changes of the CAG microsatellite in the TATA-box
      binding protein gene (TBP) were studied. We sequenced the microsatellite of the
      TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and
      15 unaffected control individuals). In addition, the microsatellites were
      sequenced from individuals of 10 northern German families with at least one
      family member affected by SCA17. To study also the evolutionary history of this
      CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed
      from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar,
      Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas,
      Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i)
      Patterns of synonymous CAA interruptions in the microsatellite are characteristic
      and likely to result from selection for stabilizing the repetitive region; (ii)
      Interspecific comparisons indicate that SCA17 is likely to be a human trait. The
      most common allele in humans (37 repeats) is close to the threshold value upon
      which neurodegenerative changes can occur and may act as a repository for
      expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17
      expanded alleles can be attributed to unequal crossing over. This can explain the
      rare and sporadic de novo generation of SCA17 alleles.

PMID- 17033686
TI  - A two base pair deletion in the PQBP1 gene is associated with microphthalmia,
      microcephaly, and mental retardation.
AB  - X-linked mental retardation has been traditionally divided into syndromic (S
      XLMR) and non-syndromic forms (NS-XLMR), although the borderlines between these
      phenotypes begin to vanish and mutations in a single gene, for example PQBP1, can
      cause S-XLMR as well as NS-XLMR. Here, we report two maternal cousins with an
      apparently X-linked phenotype of mental retardation (MR), microphthalmia, choroid
      coloboma, microcephaly, renal hypoplasia, and spastic paraplegia. By multipoint
      linkage analysis with markers spanning the entire X-chromosome we mapped the
      disease locus to a 28-Mb interval between Xp11.4 and Xq12, including the BCOR
      gene. A missense mutation in BCOR was described in a family with Lenz
      microphthalmia syndrome, a phenotype showing substantial overlapping features
      with that described in the two cousins. However, no mutation in the BCOR gene was
      found in both patients. Subsequent mutation analysis of PQBP1, located within the
      delineated linkage interval in Xp11.23, revealed a 2-bp deletion, c.461_462delAG,
      that cosegregated with the disease. Notably, the same mutation is associated with
      the Hamel cerebropalatocardiac syndrome, another form of S-XLMR. Haplotype
      analysis suggests a germline mosaicism of the 2-bp deletion in the maternal
      grandmother of both affected individuals. In summary, our findings demonstrate
      for the first time that mutations in PQBP1 are associated with an S-XLMR
      phenotype including microphthalmia, thereby further extending the clinical
      spectrum of phenotypes associated with PQBP1 mutations.

PMID- 17033687
TI  - Positron emission tomography quantification of [11C]-(+)-PHNO binding in the
      human brain.
AB  - The kinetic modeling of [11C]-(+)-PHNO binding to the dopamine D2/3 receptors in
      six human volunteers using positron emission tomography (PET) is described. [11C]
      (+)-PHNO is the first agonist radioligand for the D2/3 in humans and as expected
      showed high uptake in caudate, putamen, globus pallidus (GP) and ventral
      striatum, and low uptake in cerebellum. A two-tissue compartment model (2CM) with
      four parameters was necessary to adequately fit time-activity data in all
      regions. Although a 2CM provided an excellent estimation of total distribution
      volumes, which were highly correlated with those obtained with the invasive Logan
      approach, it provided a poor identification of the k3/k4 ratios. Coupling K1/k2
      between brain regions (Method C) or fixing K1/k2 to the value obtained in
      cerebellum (Method D) enabled more stable estimates of k3/k4 as compared with an
      unconstrained 2CM. The k3/k4 obtained with Method D ranged from 0.12+/-0.03 in
      cerebellum to 3.93+/-0.77 in GP and were similar to those obtained when coupling
      K1/k2. Binding potentials (BPs) obtained using the simplified reference tissue
      model (BP(SRTM)) ranged from 2.08+/-0.34 in caudate to 3.55+/-0.78 in GP and were
      highly correlated with k3/k4 estimates obtained with Method D (r=0.98). However,
      BP(SRTM) were 11%+/-5% lower than values obtained with Method D. BPs derived
      using the noninvasive Logan approach were slightly lower but not significantly
      different than BP(SRTM). This study demonstrates that [11C]-(+)-PHNO can be used
      for the quantitative measurement of D2/3 densities and should enable further
      studies of potential D2/3 dysregulation in several important psychiatric and
      neurologic illnesses.

PMID- 17033688
TI  - Dynamics of changes in blood flow, volume, and oxygenation: implications for
      dynamic functional magnetic resonance imaging calibration.
AB  - Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood
      oxygenation level dependent (BOLD)) during functional activation are important
      for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo2)
      from calibrated functional MRI (fMRI). An important part of this process is the
      CBF/CBV relationship, which is signified by a power-law parameter: gamma=ln
      (1+DeltaCBV/CBV)/ln (1+DeltaCBF/CBF). Because of difficulty in measuring CBF and
      CBV with MRI, the value of gamma is therefore assumed to be approximately 0.4
      from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is
      important to know if the value of gamma varies after stimulation onset. We
      measured transient relationships between DeltaCBF, DeltaCBV, and DeltaBOLD by
      multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat
      somatosensory cortex during forepaw stimulation, where the stimulus duration
      ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the
      administration of the contrast agent for CBV measurements in the same subjects.
      We observed that the relationship between DeltaCBF and DeltaCBV varied
      dynamically from stimulation onset for all stimulus durations. Typically after
      stimulation onset and at the peak or plateau of the DeltaCBF, the value of gamma
      ranged between 0.1 and 0.2. However, after stimulation offset, the value of gamma
      increased to 0.4 primarily because of rapid and slow decays in DeltaCBF and
      DeltaCBV, respectively. These results suggest caution in using dynamic
      measurements of DeltaCBF and DeltaBOLD required for calculating DeltaCMRo2 for
      functional stimulation, when either DeltaCBV has not been accurately measured or
      a fixed value of gamma during hypercapnia perturbation is used.

PMID- 17033689
TI  - Vascular response to hypoxic preconditioning in the immature brain.
AB  - We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature
      in the immature brain and thereby affects the cerebral blood flow (CBF) during a
      subsequent hypoxic-ischemic (HI) insult. On postnatal day 6 rats were exposed to
      hypoxia (36 degrees C, 8.0% O2) or normoxia for 3 h. Unilateral HI (unilateral
      carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was
      measured with the 14C-iodoantipyrine technique (at the end of HI) or with laser
      Doppler flowmetry (Perimed PF5001) before and during HI. At 0, 2, 8, and 24 h
      cerebral cortex was sampled and analyzed with gene arrays (Affymetrix 230 2.0). L
      nitroarginine or vehicle was administrated before hypoxic PC or 30 mins before HI
      followed by CBF measurement (laser Doppler) during subsequent HI. Twenty-four
      hours after PC animals were perfusion-fixed and brains immunolabeled for von
      Willebrand factor and vascular density was determined by stereological
      quantification. The decrease in CBF during HI was attenuated significantly in PC
      versus control animals (P<0.01), as detected by both techniques. Several vascular
      genes (Angpt2, Adm, Apln, Vegf, Flt1, Kdr, Pdgfra, Agtrap, Adora2a, Ednra,
      serpine1, caveolin, Id1, Prrx1, Ero1l, Acvrl1, Egfl7, Nudt6, Angptl4, Anxa2, and
      NOS3) were upregulated and a few (Csrp2, Adora2b) were downregulated after PC. A
      significant increase in vascular density (P<0.05) was seen after PC. Nitric oxide
      synthase inhibition did not affect CBF during HI after PC. In conclusion, hypoxic
      PC upregulates vascular genes, increases vascular density and attenuates the
      decrease of CBF during a subsequent HI, which could contribute to tolerance.

PMID- 17033690
TI  - Myelin-associated inhibitory signaling and strategies to overcome inhibition.
AB  - Numerous studies in the last two decades have resulted in significant progress in
      our understanding of the role of inhibitors on axonal regeneration and conditions
      that influence mature neurons to regrow in an inhibitory environment. These
      studies have revealed putative therapeutic targets and strategies to interfere in
      the inhibitory signaling cascade and promote axonal regeneration. Some agents
      that were successful in animal models are now being tested in human patients. All
      of these advances have raised hope of a cure for an injury that was once thought
      to be 'an ailment for which nothing is done' (Quote from Edwin Smith surgical
      papyrus, 1600BC).

PMID- 17033691
TI  - Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via
      endothelial mechanisms.
AB  - Rho-kinase is a serine threonine kinase that increases vasomotor tone via its
      effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces
      cerebral infarct size in wild type, but not endothelial nitric oxide synthase
      deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation
      under hypoxic/ischemic conditions and impaired vasodilation because of
      downregulation of eNOS activity. To further implicate Rho-kinase in impaired
      vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat
      and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished
      acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor
      hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore,
      hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs
      vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would
      acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce
      infarct size. To test this, we studied the acute cerebral hemodynamic effects of
      Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral
      artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle
      flowmetry. When administered 60 mins before or immediately after dMCAO, Rho
      kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely
      ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit
      in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is
      primarily endothelium-dependent, and not mediated by its direct vasodilator
      effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively
      regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF
      deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by
      small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in
      acute stroke.

PMID- 17033692
TI  - Imaging of brain hypoxia in permanent and temporary middle cerebral artery
      occlusion in the rat using 18F-fluoromisonidazole and positron emission
      tomography: a pilot study.
AB  - In acute stroke, the target of therapy is the severely hypoxic but salvageable
      tissue. Previous human studies using 18F-fluoromisonidazole and positron emission
      tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue
      hypoxia, which had normalized at repeat scan >48 h later. In the only validation
      study of 18F-FMISO, using ex vivo autoradiography in thread middle cerebral
      artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h
      after reperfusion, raising questions about the use of 18F-FMISO as a hypoxia
      tracer. Here we report a pilot study of 18F-FMISO PET in experimental stroke.
      Spontaneous hypertensive rats were subjected to distal clip MCAo. Three-hour
      dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two
      sessions: 30 mins and 48 h after clip), and 3 with temporary MCAo (45 mins, n=1;
      120 mins, n=2; scanning started 30 mins after clip removal). Experiments were
      terminated by perfusion-fixation for standard histopathology. Late tracer
      retention was assessed by both compartmental modelling and simple side-to-side
      ratios. In the initial PET session of the permanent MCAo rat, striking trapping
      of 18F-FMISO was observed in the affected cortex, which had normalized 48 h
      later; histopathology revealed pannecrosis. In contrast, there was no
      demonstrable tracer retention in either temporary MCAo models, and histopathology
      showed ischemic changes only. These results document elevated 18F-FMISO uptake in
      the stroke area only in the early phase of MCAo, but not after early reperfusion
      nor when tissue necrosis has developed. These findings strongly support the
      validity of 18F-FMISO as a marker of viable hypoxic tissue/penumbra after stroke.

PMID- 17033693
TI  - Inflammation after intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating clinical event without effective
      therapies. Increasing evidence suggests that inflammatory mechanisms are involved
      in the progression of ICH-induced brain injury. Inflammation is mediated by
      cellular components, such as leukocytes and microglia, and molecular components,
      including prostaglandins, chemokines, cytokines, extracellular proteases, and
      reactive oxygen species. Better understanding of the role of the ICH-induced
      inflammatory response and its potential for modulation might have profound
      implications for patient treatment. In this review, a summary of the available
      literature on the inflammatory responses after ICH is presented along with
      discussion of some of the emerging opportunities for potential therapeutic
      strategies. In the near future, additional strategies that target inflammation
      could offer exciting new promise in the therapeutic approach to ICH.

PMID- 17033694
TI  - Sustained neuronal activation raises oxidative metabolism to a new steady-state
      level: evidence from 1H NMR spectroscopy in the human visual cortex.
AB  - To date, functional 1H NMR spectroscopy has been utilized to report the time
      courses of few metabolites, primarily lactate. Benefiting from the sensitivity
      offered by ultra-high magnetic field (7 T), the concentrations of 17 metabolites
      were measured in the human visual cortex during two paradigms of visual
      stimulation lasting 5.3 and 10.6 mins. Significant concentration changes of
      approximately 0.2 micromol/g were observed for several metabolites: lactate
      increased by 23%+/-5% (P<0.0005), glutamate increased by 3%+/-1% (P<0.01),
      whereas aspartate decreased by 15%+/-6% (P<0.05). Glucose concentration also
      manifested a tendency to decrease during activation periods. The lactate
      concentration reached the new steady-state level within the first minute of
      activation and came back to baseline only after the stimulus ended. The changes
      of the concentration of metabolites implied a rise in oxidative metabolism to a
      new steady-state level during activation and indicated that amino-acid
      homeostasis is affected by physiological stimulation, likely because of an
      increased flux through the malate-aspartate shuttle.

PMID- 17033695
TI  - Glutamate is preferred over glutamine for intermediary metabolism in cultured
      cerebellar neurons.
AB  - The glutamate-glutamine cycle is thought to be of paramount importance in the
      mature brain; however, its significance is likely to vary with regional
      differences in distance between astrocyte and synapse. The present study is aimed
      at evaluating the role of this cycle in cultures of cerebellar neurons, mainly
      consisting of glutamatergic granule cells. Cells were incubated in medium
      containing [U-13C]glutamate or [U-13C]glutamine in the presence and absence of
      unlabeled glutamine and glutamate, respectively. Cell extracts and media were
      analyzed using high-performance liquid chromatography (HPLC) and gas
      chromatography combined with mass spectrometry (GC/MS). Both [U-13C]glutamate and
      [U-13C]glutamine were shown to be excellent precursors for synthesis of
      neuroactive amino acids and tricarboxylic acid (TCA) cycle intermediates.
      Labeling from [U-13C]glutamate was higher than that from [U-13C]glutamine in all
      metabolites measured. The presence of [U-13C]glutamate plus unlabeled glutamine
      in the experimental medium led to labeling very similar to that from [U
      13C]glutamate alone. However, incubation in medium containing [U-13C]glutamine in
      the presence of unlabeled glutamate almost abolished labeling of metabolites.
      Thus, it could be shown that glutamate is the preferred substrate for
      intermediary metabolism in cerebellar neurons. Label distribution indicating TCA
      cycle activity showed more prominent cycling from [U-13C]glutamine than from [U
      13C]glutamate. Labeling of succinate was lower than that of the other TCA cycle
      intermediates, indicating an active role of the gamma-amino butyric acid shunt in
      these cultures. It can be concluded that the cerebellar neurons rely more on
      reuptake of glutamate than supply of glutamine from astrocytes for glutamate
      homeostasis.

PMID- 17033696
TI  - Generation of gene deletions and gene replacements in Escherichia coli O157:H7
      using a temperature sensitive allelic exchange system.
AB  - In this work we describe protocols for the generation of gene deletions and gene
      replacements using a temperature sensitive plasmid in Escherichia coli O157:H7.
      This technology requires flanking DNA to be cloned into a temperature sensitive
      vector but the resulting clone allows great flexibility for further modification
      of the target sequence. It is therefore highly suited to the study of genes in
      which several rounds of changes are envisaged. A number of examples are used to
      illustrate the flexibility of the system which has been used to create novel gene
      replacements including fusions for protein localisation work and reporters for
      transcriptional analyses. In this paper we describe protocols which can be used
      with a high degree of success when applied to E. coli O157. The deletion and
      replacement of the LEE4 operon of E. coli O157 is detailed to show the advantages
      and limitations of the technology.

PMID- 17033697
TI  - Chromatin immunoprecipitation assay detects ERalpha recruitment to gene specific
      promoters in uterus.
AB  - Chromatin immunoprecipitation (ChIP) technique allows detection of proteins that
      bind to chromatin. While this technique has been applied extensively in cell
      based studies, its tissue-based application remains poorly explored. We are
      specifically interested in examining estrogen-dependent transcriptional mechanism
      in respect of recruitment of estrogen receptor-alpha (ERalpha), a ligand
      activated transcription factor, to uterine gene promoters in mice. Recent gene
      array studies, utilizing ERalpha knock-out vs. wild-type mice, have revealed that
      estrogen regulates numerous uterine genes temporally and most importantly via
      ERalpha during the phase-II response, including three well characterized genes
      viz., lactoferrin (Ltf), progesterone receptor (Pgr) and cyclinD1 (Ccnd1). Here,
      utilizing systematic ChIP studies, we demonstrate endogenous recruitment of
      ERalpha to above uterine gene promoters following estradiol-17beta (E(2))
      injection in mice.

PMID- 17033698
TI  - Combining genetic and biochemical approaches to identify functional molecular
      contact points.
AB  - Protein-protein interactions are required for many viral and cellular functions
      and are potential targets for novel therapies. Here we detail a series of genetic
      and biochemical techniques used in combination to find an essential molecular
      contact point on the duck hepatitis B virus polymerase. These techniques include
      differential immunoprecipitation, mutagenesis and peptide competition. The
      strength of these techniques is their ability to identify contact points on
      intact proteins or protein complexes employing functional assays. This approach
      can be used to aid identification of putative binding sites on proteins and
      protein complexes which are resistant to characterization by other methods.

PMID- 17033700
TI  - Recent developments in the field of organic heterobimetallic compounds of the
      alkaline-earth metals.
AB  - Heterobimetallic compounds of the alkaline-earth metals show a wide structural
      variety with strongly differing reactivity patterns. The combination of magnesium
      and alkali metal amides yields cyclic molecules with an extreme high reactivity
      which often are considered as "inverse crowns" with the metal atoms as
      coordination sites for Lewis bases. In other metallates of the alkaline-earth
      metals an activation of alkyl groups succeeds. In alkaline-earth metal zincates
      an inverse coordination of the type M(2)[(mu-R)(2)ZnR](2) is observed and the
      alkyl groups are in bridging positions between zinc and the s-block metals thus
      forming a very reactive M-C-Zn three-center-two-electron bond. Furthermore, the
      metals of the carbon group form alkaline-earth metal-silicon, -germanium and -tin
      bonds or, in the presence of very strong Lewis bases, even solvent-separated ion
      pairs. For electronegative substituents at tin an inverse coordination mode such
      as M[(mu-R)(2)SnR](2) is observed.

PMID- 17033701
TI  - Red-shifted luminescence from naphthalene-containing ligands due to pi-stacking
      in self-assembled coordination cages.
AB  - Incorporation of ligands containing substituted naphthalene cores into
      coordination cages results in extensive aromatic pi-stacking between ligands;
      this results in a red-shifted 'excimer-like' luminescence component from the
      naphthyl groups compared to the free ligands, which is diagnostic of, and can be
      used to monitor, cage assembly.

PMID- 17033699
TI  - Addressing fluorogenic real-time qPCR inhibition using the novel custom Excel
      file system 'FocusField2-6GallupqPCRSet-upTool-001' to attain consistently high
      fidelity qPCR reactions.
AB  - The purpose of this manuscript is to discuss fluorogenic real-time quantitative
      polymerase chain reaction (qPCR) inhibition and to introduce/define a novel
      Microsoft Excel-based file system which provides a way to detect and avoid
      inhibition, and enables investigators to consistently design dynamically-sound,
      truly LOG-linear qPCR reactions very quickly. The qPCR problems this invention
      solves are universal to all qPCR reactions, and it performs all necessary qPCR
      set-up calculations in about 52 seconds (using a pentium 4 processor) for up to
      seven qPCR targets and seventy-two samples at a time - calculations that commonly
      take capable investigators days to finish. We have named this custom Excel-based
      file system "FocusField2-6GallupqPCRSet-upTool-001" (FF2-6-001 qPCR set-up tool),
      and are in the process of transforming it into professional qPCR set-up software
      to be made available in 2007. The current prototype is already fully functional.

PMID- 17033702
TI  - Can an ancillary ligand lead to a thermodynamically stable end-on 1 : 1 Cu-O2
      adduct supported by a beta-diketiminate ligand?
AB  - The finding that dioxygen binds end-on to the Cu(B) site in the crystal structure
      of a precatalytic complex of peptidylglycine alpha-hydroxylating monooxygenase
      has spurred the search for biomimetic model complexes exhibiting the same
      dioxygen coordination. Recent work has not only indicated that sterically
      hindered beta-diketiminate ligands (L(1)) could support side-on 1 : 1 Cu-O(2)
      adducts, but also that an end-on L(1)Cu(THF)O(2) structure occurs as an unstable
      intermediate in the oxygenation mechanism of the Cu(I) complex. In this work,
      density functional theory and multireference methods are used to determine the
      potential of ancillary ligands, X, other than THF to yield thermodynamically
      stable end-on L(1)CuXO(2) species. A diverse set of ligands X, comprising
      phosphines, thiophene, cyclic ethers, acetonitrile, para-substituted pyridines, N
      heterocyclic carbenes, and ligands bearing hydrogen bond donors, has been
      considered in order to identify ligand characteristics which energetically favor
      end-on L(1)CuXO(2) over: a) reversion to the Cu(I) complex and dioxygen, b)
      isomerization to side-on L(1)CuXO(2), and c) decay to L(1)CuO(2) and X. Ancillary
      ligands with judiciously chosen degrees and orientation of steric bulk and which
      bear potential hydrogen bond donors to an end-on bound dioxygen moiety most favor
      oxygenation of L(1)CuX to yield end-on L(1)CuXO(2). Conversion to the side-on
      isomer can be deterred through the use of a sufficiently bulky ligand X, such as
      one that is at least the size of a 5-membered ring. Loss of X to give L(1)CuO(2)
      can be made prohibitively endergonic by employing ligands X which are highly
      electron donating and which backbond strongly with and sigma-donate significantly
      to copper.

PMID- 17033703
TI  - Silver(I) complexation of linked 2,2'-dipyridylamine derivatives. Synthetic,
      solvent extraction, membrane transport and X-ray structural studies.
AB  - Synthesis of the 2,2'-dipyridylamine derivatives di-2-pyridylaminomethylbenzene
      1, 1,2-bis(di-2-pyridylaminomethyl)benzene 2, 1,3-bis(di-2
      pyridylaminomethyl)benzene 3, 2,6-bis(di-2-pyridylaminomethyl)pyridine 4, 1,4
      bis(di-2-pyridylaminomethyl)benzene 5, and 1,3,5-tris(di-2
      pyridylaminomethyl)benzene 6 are reported together with the single-crystal X-ray
      structures of 2, 3, and 5. Reaction of individual salts of the type AgX (where X
      = NO(3)(-), PF(6)(-), ClO(4)(-), or BF(4)(-)) with the above ligands has led to
      the isolation of thirteen Ag(I) complexes, nine of which have also been
      characterised by X-ray diffraction. In part, the inherent flexibility of the
      respective ligands has resulted in the adoption of a range of coordination
      arrangements. A series of liquid-liquid (H(2)O/CHCl(3)) extraction experiments of
      Ag(I) with varying concentrations of 1-6 in the organic phase have been
      undertaken, with the counter ion in the aqueous phase being respectively picrate,
      perchlorate and nitrate. In general, extraction efficiencies for a given
      ionophore followed the Hofmeister order of picrate > perchlorate > nitrate; in
      each case the tris-dpa derivative 6 acting as the most efficient extractant of
      the six systems investigated. Competitive seven-metal bulk membrane transport
      experiments (H(2)O/CHCl(3)/H(2)O) employing the above ligands as the ionophore in
      the organic phase and equimolar concentrations of Co(II), Ni(II), Zn(II), Cu(II),
      Cd(II), Pb(II) and Ag(I) in the aqueous source phase were also undertaken, with
      transport occurring against a pH gradient. Under the conditions employed 1 and 5
      yielded negligible transport of any of the metals present in the source phase
      while sole transport selectivity for Ag(I) was observed for 2-4 and 6.

PMID- 17033704
TI  - The reaction of tertiary phosphines with (Ph2Se2I2)2--the influence of steric and
      electronic effects.
AB  - The reaction of (Ph(2)Se(2)I(2))(2) with a wide variety of tertiary phosphines
      possessing different steric and electronic properties has been studied, leading
      in most cases to R(3)PSe(Ph)I adducts; [R(3)P = (p-CH(3)C(6)H(4))(3)P (1), (m
      CH(3)C(6)H(4))(3)P (2), (o-OCH(3)C(6)H(4))(3)P (4), Ph(2)MeP (6), Me(2)PhP (7),
      Me(3)P (8), Cy(3)P (9)]. All of the products formed were characterised by
      elemental analysis, Raman and multinuclear NMR spectroscopy. Both steric and
      electronic factors are important in determining the structural motif (CT vs.
      ionic) observed in the solid-state. In general, highly basic phosphines result in
      a lengthening of the Se-I interaction, and a preference for an ionic structure.
      The reaction with (o-CH(3)C(6)H(4))(3)P does not yield a stable R(3)PSe(Ph)I
      adduct, and instead (o-CH(3)C(6)H(4))(3)PI(2) (3) is formed. The unusually long P
      I bond, [2.5523(12) A], and short I-I bond, [3.0724(4) A], exhibited by is a
      result of the high steric requirements of this phosphine. The similarly bulky (o
      SCH(3)C(6)H(4))(3)P yields a mixture of (o-SCH(3)C(6)H(4))(3)PSe(Ph)I (5a) and
      [(o-SCH(3)C(6)H(4))(3)PSePh]I(3) (5b). The crystal structures of (m
      CH(3)C(6)H(4))(3)PSe(Ph)I, 2, (o-CH(3)C(6)H(4))(3)PI(2), 3, [(o
      OCH(3)C(6)H(4))(3)PSePh]I.CH(2)Cl(2), 4, [(o-SCH(3)C(6)H(4))(3)PSePh]I(3), 5b,
      two pseudo-polymorphs of Ph(2)MePSe(Ph)I, 6a/6b, and
      [Me(3)PSe(Ph)I](2).CH(2)Cl(2), 8, are reported. The R(3)PSe(Ph)I adducts formed
      exhibit one of four types of behaviour. Type I products, (such as 2) are CT in
      the solid-state and display fluxionality in solution. Type II products (such as
      6a/6b) lie close to the CT/ionic structural borderline, displaying long Se-I
      bonds, and are more appropriately classified as [R(3)PSePh] (acceptor)/I(-)
      (donor) CT complexes. Type II complexes ionise in solution to [R(3)PSePh]I. Type
      III products, such as 8, are ionic in solution, but frequently show cation-anion,
      or cation-solvent interactions in the solid-state, although these interactions
      are weak and the linear P-Se-I motif is lost. Type IV products (such as 4) are
      ionic and feature bulky phosphines. They display no short cation-anion
      interactions in the solid-state.

PMID- 17033705
TI  - Spectroelectrochemical evidence for communication within a laterally-bridged
      dimanganese(III) bis-porphyrin.
AB  - Electronic coupling between the porphyrin units of a laterally-bridged
      dimanganese(III) bis-porphyrin 2 is explored using electrochemistry,
      spectroelectrochemistry and resonance-Raman spectroscopy. It is found that strong
      electronic interactions between the manganese(III) ion and the porphyrin
      macrocycle enhance the perturbations experienced by these bis-porphyrin systems
      when compared to related monomer porphyrin systems. In turn this leads to
      effective electronic communication between the manganese ions in the bis
      porphyrin. This finding has importance in the design of molecular wires based on
      laterally-bridged oligo-metallo-porphyrins.

PMID- 17033706
TI  - Synthesis and structures of acyclic monoanionic tetradentate aza beta
      diketiminate complexes of magnesium, zinc, and cadmium.
AB  - An acyclic monoanionic tetradentate nitrogen ligand was prepared through the
      condensation of 2-(4-tolyl)-malondialdehyde and 8-aminoquinoline to give
      (BDI(QQ))H where (BDI(QQ))H = (8-quinolyl)-NCHC(4-tolyl)CHNH-(8-quinolyl). Metal
      complexes, (BDI(QQ))MX, were prepared where MX = MgBr 2, ZnCl 3, and CdOAc 4. The
      spectroscopic and crystallographic properties of compounds 2, 3, and 4 were
      explored. Structures of complexes 2, 3, 4, and the tridentate ligand, (BDI(Q))OH,
      5, are reported.

PMID- 17033707
TI  - Allosteric effects in asymmetric hydrogenation catalysis? Asymmetric induction as
      a function of the substrate and the backbone flexibility of C1-symmetric
      diphosphines in rhodium-catalysed hydrogenations.
AB  - The new unsymmetrical, optically active ligands 1,2-C(2)H(4)(PPh(2))(2'R,5'R
      2',5'-dimethylphospholanyl) (L(a)) and 1,3-C(3)H(6)(PPh(2))(2'R,5'R-2',5'
      dimethylphospholanyl) (L(b)) form complexes of the type
      [Rh(L)(cyclooctadiene)][BF(4)] where L = L(a) (1a) or L(b) (1b), [PtCl(2)(L)]
      where L = L(a) (2a) or L(b) (2b) and [PdCl(2)(L)] where L = L(a) (3a) or Lb (3b).
      The crystal structures of 2a and 2b show the chelate ligand backbones adopt delta
      twist and flattened chair conformations respectively. Asymmetric hydrogenation of
      enamides and dehydroaminoesters using 1a and 1b as catalysts show that the
      ethylene-backboned diphosphine L(a) gives a more efficient catalyst in terms of
      asymmetric induction than the propylene-backboned analogue L(b). The greatest
      enantioselectivities were obtained with 1a and enamide substrates with ees up to
      91%. Substrate-induced conformational changes in the Rh-diphosphine chelates are
      proposed to explain some of the ees observed in the hydrogenation of enamides.

PMID- 17033708
TI  - Thermodynamics and the structural aspects of the ternary complexes of Am(III),
      Cm(III) and Eu(III) with Ox and EDTA + Ox.
AB  - The stability constants and the associated thermodynamic parameters of formation
      of the binary and the ternary complexes of Am(3+), Cm(3+) and Eu(3+) were
      determined by a solvent extraction to measure the variation in the distribution
      coefficient with temperature (0-60 degrees C) for aqueous solutions of I = 6.60 m
      (NaClO(4)). The formation of ternary complexes is favored by both the enthalpy
      (exothermic) and the entropy (endothermic) values. (13) C NMR, TRLFS and EXAFS
      spectral data was used to study the coordination modes of the ternary complexes.
      In the formation of the complex M(EDTA)(Ox)(3-), the EDTA retained all its
      coordination sites with Ox binding via two carboxylates and with one water of
      hydration remaining attached to the M(3+). In the complex M(EDTA)(Ox)(2)(5-), one
      carboxylate, either from EDTA or Ox, is not bounded to M(3+) and there were no
      water of hydration attached to these cations.

PMID- 17033709
TI  - Complexes of 1,2-bis(aryl-imino)acenaphthene (Ar-BIAN) ligands with some heavy p
      block elements.
AB  - The new Ar-BIAN complexes [(mes-BIAN)InCl(3)(THF)] (1), [(mes-BIAN)(2)Tl][PF(6)]
      (2), [(dipp-BIAN)SnCl(4)] (3), [(dipp-BIAN)SbCl(3)] (4), [(dipp-BIAN)BiCl(3)] (5)
      and [(mes-BIAN)BiCl(3)] (6) have been prepared by treatment of the neutral mes-
      and dipp-substituted BIAN ligands with the p-block reagents InCl(3), TlPF(6),
      SnCl(4), SbCl(3), and BiCl(3). The molecular structures of complexes 1-6 have
      been determined by single-crystal X-ray diffraction methods. However, only the
      atom connectivity was established for 5.

PMID- 17033710
TI  - Alkene cyclopropanation catalyzed by Halterman iron porphyrin: participation of
      organic bases as axial ligands.
AB  - With the iron(III) complex of the Halterman iron porphyrin [P*Fe(Cl)] and ethyl
      diazoacetate (EDA) as catalyst and carbene source, respectively, styrene-type
      substrates were converted to cyclopropyl esters with high trans/cis ratio (not
      less than 12) and high enantioselectivity for the trans-isomers (74-86% ee). The
      isomeric distribution of the cyclopropyl esters so obtained is akin to that
      obtained from the previously reported Ru(II) counterpart [P*Ru(CO)]. A linear
      Hammett correlation log(k(X)/k(H)) = sigma(+)rho was observed with rho = -0.57
      suggesting the involvement of an electrophilic cyclopropanating species derived
      from the iron(II) center as the reactive intermediate in the catalytic cycle.
      This is further supported by a dramatic decrease in the enantioselectivity and
      trans/cis ratio observed in an experiment of styrene cyclopropanation when the
      reaction mixture was deliberately exposed to air. Axial ligand effects on the
      selectivities was also investigated. Substantial improvement in trans/cis ratios
      could be achieved by addition of organic bases such as pyridine (py) and 1
      methylimidazole (MeIm) to the catalytic reaction. The existence of axially
      ligated iron carbene moieties, [P*Fe(CHCO(2)Et)(py)] and [P*Fe(CHCO(2)Et)(MeIm)],
      was established by electrospray mass spectrometry. Study of secondary kinetic
      isotope effect indicated that a more product-like transition state was generated
      by addition of MeIm.

PMID- 17033711
TI  - Synthetic and structural comparisons of bismuth(III) carboxylates synthesised
      under solvent-free and reflux conditions.
AB  - Two synthetic approaches to the formation of bismuth(III) carboxylates have been
      explored and compared. Ph(3)Bi was reacted with a series of carboxylic acids
      (RCO(2)H) of varying pK(a) and functionality (R = PhCH[double bond, length as m
      dash]CH, o-MeOC(6)H(4), m-MeOC(6)H(4), o-H(2)NC(6)H, o-O(2)NC(6)H(4), p
      O(2)NC(6)H(4), 2-(C(5)H(4)N)) under reflux conditions in toluene and solvent
      free. The thermochemical profiles of the solvent-free reactions were also studied
      by DSC-TGA. All reactions produced the tri-substituted bismuth carboxylates in
      comparable yields and purity with the exceptions of picolinic acid and p
      nitrobenzoic acid. 2-Picolinic acid exclusively formed the di-substituted
      complex, [PhBi(2-(C(5)H(4)N)CO(2))(2)](4), by both methods, while p-nitrobenzoic
      acid gave the tri-substituted complex through reflux and the di-substituted
      complex under solvent-free conditions. Two of the complexes were structurally
      authenticated by single crystal X-ray diffraction: [PhBi(2
      (C(5)H(4)N)CO(2))(2)](4) is tetrameric formed through five membered chelate rings
      involving the pyridyl N and O(-C) rather than the less stable carboxylate (
      CO(2)) chelates, while [Bi(o-MeOC(6)H(4)CO(2))(3)](infinity), is a polymer in
      which dimeric units, constructed around two chelating and one unsymmetrical
      bridging carboxylate on each Bi centre, are then joined together through longer
      intermolecular Bi-O bridging bonds.

PMID- 17033712
TI  - Quantitative determination of cucumber mosaic virus genome RNAs in virions by
      real-time reverse transcription-polymerase chain reaction.
AB  - A real-time RT-PCR procedure using the green fluorescent dye SYBR Green I was
      developed for determining the absolute and relative copies of cucumber mosaic
      virus (CMV) genomic RNAs contained in purified virions. Primers specific to each
      CMV ORF were designed and selected. Sequences were then amplified with length
      varying from 61 to 153 bp. Using dilution series of CMV genome RNAs prepared by
      in vitro transcription as the standard samples, a good linear correlation was
      observed between their threshold cycle (Ct) values and the logarithms of the
      initial template amounts. The copies of genomic RNA 1, RNA 2, RNA 3 and the
      subgenomic RNA 4 in CMV virions were quantified by this method, and the ratios
      were about 1.00:1.17:3.58:5.81. These results were confirmed by Lab-on-a-chip and
      northern blot hybridization assays. Our work is the first report concerning the
      relative amounts of different RNA fragments in CMV virions as a virus with
      tripartite genome.

PMID- 17033713
TI  - Up-regulation of cartilage oligomeric matrix protein gene expression by insulin
      like growth factor-I revealed by real-time reverse transcription-polymerase chain
      reaction.
AB  - Cartilage oligomeric matrix protein (COMP) strengthens cartilage by binding to
      type II and type IX collagen-forming bridges between collagen fibrils. It was
      hypothesized that perhaps one or more anabolic growth factors such as insulin
      like growth factor-I (IGF-I), fibroblast growth factor-1 (FGF-1) or platelet
      derived growth factor-BB (PDGF-BB) increase COMP gene expression. Their effects
      on primary human chondrocytes and the chondrogenic cell line ATDC5 were studied
      using real time reverse transcript-polymerase chain reaction (RT-PCR) for
      quantification. IGF-I, but not the FGF-1 or PDGF-BB, up-regulated COMP gene
      expression by approximate 5-fold in human adult chondrocytes in a dose- and time
      dependent manner. IGF-I exerted similar effects on ATDC5 cells. Results from
      these real time RT-PCR experiments were confirmed by transfecting into ATDC5
      cells a full-length mouse COMP promoter cloned upstream of a luciferase reporter
      gene. On stimulation with IGF-I, the luciferase reporter activity increased by
      about eight times. In conclusion, IGF-I seems to be an important positive
      regulator of COMP, which may play an important role in an attempted repair of
      either traumatized or degenerated cartilage.

PMID- 17033714
TI  - Immunological properties of recombinant Mycobacterium bovis bacillus Calmette
      Guerin strain expressing fusion protein IL-2-ESAT-6.
AB  - The live vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) provides
      variable efficacy against adult pulmonary tuberculosis (TB). Recombinant BCG,
      expressing either immunodominant antigens or Th1 cytokines, is a promising
      strategy for developing a new TB vaccine. However, not much is known about
      whether the introduction of cytokine and specific antigen genes concurrently into
      the BCG strain could improve the immunogenicity of BCG. In this study, a
      recombinant BCG strain (rBCG) expressing the fusion protein human interleukin
      (IL)-2 and ESAT-6 (early secreted antigenic target-6 kDa) antigen of
      Mycobacterium tuberculosis was constructed. Six weeks after BALB/c mice (H-2d)
      were immunized with 106 colony forming units (CFUs) BCG or rBCG, splenocyte
      proliferation was determined with MTT [3-(4,5-dimethylthiazolyl-2)-2, 5
      diphenyltetrazolium bromide] assay, IL-4 and interferon (IFN)-gamma produced by
      splenocytes were tested by enzyme linked immunosorbent assay (ELISA,) and the
      cytotoxicity of splenocytes from immunized mice to P815 cells (H-2d) expressing
      ESAT-6 protein was measured using CytoTox 96 Non-Radioactive Cytotoxicity Assay.
      Compared with native BCG-vaccinated mice, rBCG induced stronger Th1 responses
      that were confirmed by high lymphoproliferative responses and IFN-gamma
      production to culture filtrate protein (CFP) or ESAT-6 protein. Moreover, rBCG
      induced significant enhanced CTL responses against P815-ESAT-6 cells. Results
      from rBCG-immunized mice demonstrated that introducing the il-2 and esat-6 genes
      into BCG could enhance Th1 type immune responses to ESAT-6. Further investigation
      is needed by introducing other Th1 cytokines and antigens into BCG to optimize
      the protective efficacy against TB.

PMID- 17033715
TI  - Studies on the temperature effect on bacteriorhodopsin of purple and blue
      membrane by fluorescence and absorption spectroscopy.
AB  - Fluorescence and absorption spectra were used to study the temperature effect on
      the conformation of bacteriorhodopsin (bR) in the blue and purple membranes
      (termed as bRb and bRp respectively). The maximum emission wavelengths of
      tryptophan fluorescence in both proteins at room temperature are 340 nm, and the
      fluorescence quantum yield of bRb is about 1.4 fold higher than that of bRp. As
      temperature increases, the tryptophan fluorescence of bRb decreases, while the
      tryptophan fluorescence of bRp increases. The binding study of extrinsic
      fluorescent probe bis-ANS indicated that the probe can bind only to bRb, but not
      to bRp. These results suggest that significant structural difference existed
      between bRb and bRp. It was also found that both kinds of bR are highly thermal
      stable. The maximum wavelength of the protein fluorescence emission only shifted
      from 340 nm to 346 nm at 100 degrees C. More interestingly, as temperature
      increased, the characteristic absorption peak of bRb at 605 nm decreased and a
      new absorption peak at 380 nm formed. The transition occurred at a narrow
      temperature range (65 degrees C-70 degrees C). These facts indicated that an
      intermediate can be induced by high temperature. This phenomenon has not been
      reported before.

PMID- 17033716
TI  - Expression of basic fibroblast growth factor results in the decrease of myostatin
      mRNA in murine C2C12 myoblasts.
AB  - During the development and regeneration of skeletal muscle, many growth factors,
      such as basic fibroblast growth factor (bFGF, FGF-2) and myostatin, have been
      shown to play regulating roles. bFGF contributes to promote proliferation and to
      inhibit differentiation of skeletal muscle, whereas myostatin plays a series of
      contrasting roles. In order to elucidate whether the expression of bFGF has any
      relationship with the expression of myostatin in skeletal muscle cells, we
      constructed a eukaryotic expression vector for the expression of exogenous bFGF
      in murine C2C12 myoblasts. Quantitative RT-PCR assays indicated that with the
      increase of the expression of exogenous bFGF gene, the expression of endogenous
      myostatin gene was suppressed at mRNA level and protein level.

PMID- 17033717
TI  - Bcl-XL small interfering RNA enhances sensitivity of Hepg2 hepatocellular
      carcinoma cells to 5-fluorouracil and hydroxycamptothecin.
AB  - Changes in drug sensitivity in Bcl-XL small interfering RNA (siRNA) transfected
      Hepg2 hepatocellular carcinoma cells were investigated in this study. Bcl-XL
      siRNA and negative siRNA expression vector were constructed and stably
      transfected into Hepg2 cells. Reverse transcription (RT)-PCR, western blot and
      immunofluorescence were used to detect the target gene expression at mRNA and
      protein levels. Drug sensitivity of the cells to 5-fluorouracil (5-FU) and
      hydroxycamptothecin (HCPT) were evaluated with MTT. The Bcl-XL mRNA and protein
      expression levels in Bcl-XL siRNA transfectants were reduced compared with
      negative siRNA transfectants or mock cells. MTT results showed that Bcl-XL siRNA
      transfected cells have a higher cell inhibition rate than negative vector
      transfected cells or untreated cells after treatment with 13, 130, 1300 and
      13,000 mg/L of 5-FU. Bcl-XL siRNA transfected cells also showed increased drug
      sensitivity compared with negative vector transfected cells or untreated cells
      after treatment with 0.18, 0.36, 0.72 and 1.44 mg/L HCPT. Flow cytometry (FCM)
      results demonstrated that the sub-G1 population increased in the Bcl-XL siRNA
      group, compared with the negative siRNA group and untreated control group, after
      the addition of 5-FU (1300 mg/L) and HCPT (0.72 mg/L). siRNA targeting Bcl-XL
      gene can specifically down-regulate Bcl-XL expression in Hepg2 cells, and can
      increase spontaneous cell apoptosis and sensitize cells to 5-FU or HCPT.

PMID- 17033718
TI  - Model for unidirectional movement of axonemal and cytoplasmic dynein molecules.
AB  - A model for the unidirectional movement of dynein is presented based on the
      structural observations and biochemical experimental results available. In this
      model, the binding affinity of dynein for microtubule (MT) is independent of its
      nucleotide state and the change between strong and weak MT-binding is determined
      naturally by the variation of relative orientation between the stalk and MT, as
      the stalk rotates following nucleotide-state transition. Thus the enigmatic
      communication from the adenosine triphosphate (ATP)-binding site in the globular
      domain to the far MT-binding site in the tip of the stalk, which is a
      prerequisite in conventional models, is not required. Using the present model,
      the previous experimental results such as the effect of ATP and adenosine
      diphosphate (ADP) bindings on dissociation of dynein from MT, the movement of
      single-headed axonemal dyneins at saturating ATP concentration, the load
      dependence of step-size for the movement of two-headed cytoplasmic dyneins and
      the dependence of stall force on ATP concentration can be well explained.

PMID- 17033719
TI  - Ubiquinone (coenzyme Q) biosynthesis in Chlamydophila pneumoniae AR39:
      identification of the ubiD gene.
AB  - Ubiquinone is an essential electron carrier in prokaryotes. Ubiquinone
      biosynthesis involves at least nine reactions in Escherichia coli. 3-octaprenyl-4
      hydroxybenzoate decarboxylase (UbiD) is an important enzyme on the pathway and
      deletion of the ubiD gene in E. coli gives rise to ubiquinone deficiency in vivo.
      A protein from Chlamydophila pneumoniae AR39 had significant similarity compared
      with protein ubiD from E. coli. Based on this information, the protein-encoding
      gene was used to swap its counterpart in E. coli, and gene expression in
      resultant strain DYC was confirmed by RT-PCR. Strain DYC grew using succinate as
      carbon source and rescued ubiquinone content in vivo, while ubiD deletion strain
      DYD did not. Results suggest that the chlamydial protein exerts the function of
      UbiD.

PMID- 17033720
TI  - Establishment and application of a TaqMan real-time quantitative reverse
      transcription-polymerase chain reaction assay for rubella virus RNA.
AB  - The aim of this study was to establish and apply a real-time quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) for rubella virus (RV) RNA.
      First, the primer and TaqMan probe concentrations, as well as reaction
      temperatures were optimized to establish an efficient real-time quantitative RT
      PCR assay for RV RNA. Next, an RV-specific PCR amplicon was made as an external
      standard to estimate the linearity, amplification efficiency, analytical
      sensitivity and reproducibility of the real time quantitative assay. Finally, the
      assay was applied to quantify RV RNA in clinical samples for rubella diagnosis.
      The RV-specific PCR amplicon was prepared for evaluation of the assay at 503 bp,
      and its original concentration was 2.75x109 copies/mul. The real time
      quantitative assay was shown to have good linearity (R2=0.9920), high
      amplification efficiency (E=1.91), high sensitivity (275 copies/ml), and high
      reproducibility (variation coefficient range, from 1.25% to 3.58%). Compared with
      the gold standard, the specificity and sensitivity of the assay in clinical
      samples was 96.4% and 86.4%, respectively. Therefore, the established
      quantitative RT-PCR method is a simple, rapid, less-labored, quantitative, highly
      specific and sensitive assay for RV RNA.

PMID- 17033721
TI  - In vitro reassembly of tobacco ribulose-1,5-bisphosphate carboxylase/oxygenase
      from fully denatured subunits.
AB  - It has been generally proved impossible to reassemble ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) from fully denatured subunits in vitro in higher
      plant, because large subunit of fully denatured Rubisco is liable to precipitate
      when the denaturant is removed by common methods of direct dilution and one-step
      dialysis. In our experiment, the problem of precipitation was resolved by an
      improved gradual dialysis method, which gradually decreased the concentration of
      denaturant. However, fully denatured Rubisco subunits still could not be
      reassembled into holoenzyme using gradual dialysis unless chaperonin 60 was
      added. The restored activity of reassembled Rubisco was approximately 8% of
      natural enzyme. The quantity of reassembled Rubisco increased greatly when heat
      shock protein 70 was present in the reassembly process. ATP and Mg2+ were
      unnecessary for in vitro reassembly of Rubisco, and Mg2+ inhibited the reassembly
      process. The reassembly was weakened when ATP, Mg2+ and K+ existed together in
      the reassembly process.

PMID- 17033722
TI  - Self-reported lifetime physical activity and areal bone mineral density in
      healthy postmenopausal women: the importance of teenage activity.
AB  - Girls who exercise athletically have higher bone mass than their sedentary
      counterparts, and this difference may be sustained in adulthood. However, whether
      moderate physical activity during youth confers lasting benefits for bone is
      unclear. We explored lifetime physical activity and current areal bone mineral
      density (aBMD) in 78 postmenopausal women with no known history of osteoporosis.
      Subjects reported physical activity for four age periods (12-18, 19-34, 35-49, >
      or = 50 years) using the Historical Leisure Activity Questionnaire, completed two
      3-day food records, had measurements of height and weight, and aBMD assessed
      using dual-energy X-ray absorptiometry at the lumbar spine (L1-4) and proximal
      femora. Low aBMD was detected at the lumbar spine in 43 (56%) women and at the
      proximal femora in 38 (49%) women. Teenage physical activity, but not activity
      during other age periods, was associated with current aBMD at both sites (lumbar
      spine r = 0.31, P < 0.01; mean proximal femora r = 0.33, P < 0.01). Weight
      bearing physical activity (WBPA) at age 12-18 years was the only predictor of
      current lumbar spine aBMD (R (2) = 0.110, P = 0.004). Current proximal femoral
      aBMD was positively predicted by physical activity at age 12-18 years and
      negatively predicted by current age (R (2) = 0.175, P = 0.001). Subjects above
      the median of teen WBPA had 5-8% higher current aBMD than those reporting less
      teen WBPA and were less likely to be classified with osteopenia or osteoporosis.
      Moderate physical activity during years of peak bone acquisition appears to have
      lasting benefits for lumbar spine and proximal femoral aBMD in postmenopausal
      women.

PMID- 17033723
TI  - Ovine periodontal ligament stem cells: isolation, characterization, and
      differentiation potential.
AB  - Periodontal disease leads to destruction of the connective tissues responsible
      for restraining teeth within the jaw. To date, various conventional therapies for
      periodontal regeneration have shown limited and variable clinical outcomes.
      Recent studies have suggested that newly identified human periodontal ligament
      stem cells (PDLSCs) may offer an alternate and more reliable strategy for the
      treatment of periodontal disease using a cell-based tissue engineering approach.
      In the present study, we generated enriched preparations of PDLSCs derived from
      ovine periodontal ligament using immunomagnetic bead selection, based on
      expression of the mesenchymal stem cell-associated antigen CD106 (vascular cell
      adhesion molecule 1). These CD106+ ovine PDLSCs demonstrated the capacity to form
      adherent clonogenic clusters of fibroblast-like cells when plated at low
      densities in vitro. Ex vivo-expanded ovine PDLSCs exhibited a high proliferation
      rate in vitro and expressed a phenotype (CD44+, CD166+, CBFA-1+, collagen-I+,
      bone sialoprotein+) consistent with human-derived PDLSCs. Furthermore, cultured
      ovine PDLSCs expressed high transcript levels of the ligament/tendon-specific
      early transcription factor scleraxis. Importantly, ex vivo-expanded ovine PDLSCs
      demonstrated the capacity to regenerate both cementum-like mineral and
      periodontal ligament when transplanted into NOD/SCID mice. The results from the
      present study suggest that ovine PDLSCs may potentially be used as a novel
      cellular therapy to facilitate successful and more predictable regeneration of
      periodontal tissue using an ovine preclinical model of periodontal disease as a
      prelude to human clinical studies.

PMID- 17033724
TI  - Antiremodeling agents influence osteoblast activity differently in modeling and
      remodeling sites of canine rib.
AB  - Antiremodeling agents reduce bone loss in part through direct actions on
      osteoclasts. Their effects on osteoblasts and bone formation activity are less
      clear and may differ at sites undergoing modeling vs. remodeling. Skeletally
      mature intact beagles, 1-2 years old at the start of the study, were treated
      daily with clinically relevant doses of alendronate (0.10 or 0.20 mg/kg),
      risedronate (0.05 or 0.10 mg/kg), raloxifene (0.50 mg/kg), or vehicle (1 mL/kg).
      Dynamic bone formation parameters were histologically assessed on periosteal,
      endocortical/trabecular, and intracortical bone envelopes of the rib. Raloxifene
      significantly increased periosteal surface mineral apposition rate (MAR), a
      measure of osteoblast activity, compared to all other treatments (+108 to +175%,
      P < 0.02), while having no significant effect on MAR at either the
      endocortical/trabecular or intracortical envelope. Alendronate (both 0.10 and
      0.20 doses) and risedronate (only the 0.10 dose) significantly (P < or = 0.05)
      suppressed MAR on the endocortical/trabecular envelope, while none of the
      bisphosphonate doses significantly altered MAR at either the periosteal or
      intracortical envelopes compared to vehicle. Based on these results, we conclude
      that (1) at clinically relevant doses the two classes of antiremodeling agents,
      bisphosphonates and selective estrogen receptor modulators, exert differential
      effects on osteoblast activity in the canine rib and (2) this effect depends on
      whether modeling or remodeling is the predominant mechanism of bone formation.

PMID- 17033725
TI  - Identification of a promoter element within the zebrafish colXalpha1 gene
      responsive to runx2 isoforms Osf2/Cbfa1 and til-1 but not to pebp2alphaA2.
AB  - Type X collagen is a short chain collagen specifically expressed by hypertrophic
      chondrocytes during endochondral ossification. We report here the functional
      analysis of the zebrafish (Danio rerio) collagen Xalpha1 gene (colXalpha1)
      promoter with the identification of a region responsive to two isoforms of the
      runt domain transcription factor runx2. Furthermore, we provide evidence for the
      presence of dual promoter usage in zebrafish, a finding that should be important
      to further understanding of the regulation of its restricted tissue distribution
      and spatial-temporal expression during early development. The zebrafish
      colXalpha1 gene structure is comparable to that recently identified by
      comparative genomics in takifugu and shows homology with corresponding mammalian
      genes, indicating that its general architecture has been maintained throughout
      vertebrate evolution. Our data suggest that, as in mammals, runx2 plays a role in
      the development of the osteogenic lineage, supporting zebrafish as a model for
      studies of bone and cartilage development.

PMID- 17033726
TI  - Calvarial osteoclasts express a higher level of tartrate-resistant acid
      phosphatase than long bone osteoclasts and activation does not depend on
      cathepsin K or L activity.
AB  - Bone resorption by osteoclasts depends on the activity of various proteolytic
      enzymes, in particular those belonging to the group of cysteine proteinases. Next
      to these enzymes, tartrate-resistant acid phosphatase (TRAP) is considered to
      participate in this process. TRAP is synthesized as an inactive proenzyme, and in
      vitro studies have shown its activation by cysteine proteinases. In the present
      study, the possible involvement of the latter enzyme class in the in vivo
      modulation of TRAP was investigated using mice deficient for cathepsin K and/or L
      and in bones that express a high (long bone) or low (calvaria) level of cysteine
      proteinase activity. The results demonstrated, in mice lacking cathepsin K but
      not in those deficient for cathepsin L, significantly higher levels of TRAP
      activity in long bone. This higher activity was due to a higher number of
      osteoclasts. Next, we found considerable differences in TRAP activity between
      calvarial and long bones. Calvarial bones contained a 25-fold higher level of
      activity than long bones. This difference was seen in all mice, irrespective of
      genotype. Osteoclasts isolated from the two types of bone revealed that calvarial
      osteoclasts expressed higher enzyme activity as well as a higher level of mRNA
      for the enzyme. Analysis of TRAP-deficient mice revealed higher levels of
      nondigested bone matrix components in and around calvarial osteoclasts than in
      long bone osteoclasts. Finally, inhibition of cysteine proteinase activity by
      specific inhibitors resulted in increased TRAP activity. Our data suggest that
      neither cathepsin K nor L is essential in activating TRAP. The findings also
      point to functional differences between osteoclasts from different bone sites in
      terms of participation of TRAP in degradation of bone matrix. We propose that the
      higher level of TRAP activity in calvarial osteoclasts compared to that in long
      bone cells may partially compensate for the lower cysteine proteinase activity
      found in calvarial osteoclasts and TRAP may contribute to the degradation of
      noncollagenous proteins during the digestion of this type of bone.

PMID- 17033727
TI  - Desorption of arsenic from drinking water distribution system solids.
AB  - Previous work has shown that arsenic can accumulate in drinking water
      distribution system (DWDS) solids (Lytle et al., 2004) when arsenic is present in
      the water. The release of arsenic back into the water through particulate
      transport and/or chemical release (e.g. desorption, dissolution) could result in
      elevated arsenic levels at the consumers' tap. The primary objective of this work
      was to examine the impact of pH and orthophosphate on the chemical release (i.e.
      desorption) of arsenic from nine DWDS solids collected from utilities located in
      the Midwest. Arsenic release comparisons were based on the examination of arsenic
      and other water quality parameters in leach water after contact with the solids
      over the course of 168~hours. Results showed that arsenic was released from
      solids and suggested that arsenic release was a result of desorption rather than
      dissolution. Arsenic release generally increased with increasing initial arsenic
      concentration in the solid and increasing pH levels (in the test range of 7 to
      9). Finally, orthophosphate (3 and 5 mg PO(4)/L) increased arsenic release at all
      pH values examined. Based on the study results, utilities with measurable levels
      of arsenic present in their water should be aware that some water quality changes
      can cause arsenic release in the DWDS potentially resulting in elevated levels at
      the consumer's tap.

PMID- 17033728
TI  - Multislice computed tomographic findings of the anomalous origins of the right
      coronary artery: evaluation of possible causes of myocardial ischemia.
AB  - BACKGROUND: Anomalous right coronary arteries (RCA) arising from the left sinus
      of Valsalva may cause myocardial ischemia. OBJECTIVE: We evaluated morphological
      features of anomalous RCA by using multislice computed tomography (MSCT) in
      relation to myocardial ischemia provoked by myocardial perfusion single-photon
      emission computed tomography. METHODS: MSCT was performed in a total of 3, 212
      patients by using an Aquillion 16 and a Light Speed Ultra. Retrospective ECG
      gated image reconstruction was performed. Volume rendering, axial and curved
      multiplanar reformatted images were analyzed for the determination of the origin
      and course of the RCA, the take-off angle of the RCA from the aorta, and size of
      the RCA orifice. Furthermore, virtual angioscopic images were also used for the
      evaluation of the RCA orifice structure. RESULTS: Anomalous origins of the RCA
      were found in 15 patients. In 13 patients, the RCA arose from the left sinus of
      Valsalva, and in 2 patients it arose from the left main coronary artery as a
      single coronary artery. The RCA coursed anteriorly between the ascending aorta
      and pulmonary artery in 14 patients, whereas it had a retroaortic course in 1
      patient. Acute angle take-off (<30 degrees ) of the RCA from the aorta and the
      left main coronary artery was observed in 8 patients, intramural course of the
      RCA within the aortic wall was observed in 6 patients and a small RCA orifice was
      observed in 4 patients. Exercise-induced myocardial ischemia was present in 5
      patients. CONCLUSION: Coursing between the aorta and pulmonary artery, acute
      angle take-off and intramural course were thought to be major causes of exercise
      induced ischemia in patients with anomalous origins of the RCA.

PMID- 17033729
TI  - Sustainability in the cardiac cath lab.
AB  - Use of radiation for medical examinations and test is the largest man-made source
      of radiation exposure. Interventional procedures are only 2% of all radiological
      procedures, but contribute to about 20% of the total collective dose per head per
      year. On average, a left ventriculography and coronary angiography corresponds to
      a radiation exposure for the patient of about 300, a coronary stent to 1,000, a
      peripheral artery intervention to 1,500 to 2,500, and a cardiac radiofrequency
      ablation to 900-1,500 chest x-rays. Invasive cardiology procedures increased
      tenfold in the last ten years and growth in the field has been accompanied by
      concern for the safety of the staff. Interventional cardiologists have an
      exposure per-head per year two- to three times higher than that of radiologists,
      with an annual exposure equivalent to around 250 chest x-rays per head. A
      reduction of occupational doses by a factor of ten can be achieved simply by and
      intensive training program. The awareness of radiation effects may be suboptimal
      in the medical community. It is recommended by professional guidelines and
      reinforced by the European law that the responsibility of all physicians is to
      minimize the radiation injury hazard to their patients, to their professional
      staff and to themselves.

PMID- 17033730
TI  - Thoracoabdominal aorta coarctation with bilateral renal artery involvement:
      diagnosis with multidetector CT angiography (MDCTA).
AB  - Atypical coarctation of the descending thoracic and abdominal aorta is a very
      uncommon vascular disease. Congenital, acquired, inflammatory, and infectious
      etiologies have been proposed. Patients typically presents with uncontrolled
      secondary hypertension in the upper half of the body or hypotension in the lower
      extremities in the first three decades of their lives. We report the case of a 20
      year-old man with severe hypertension. Diffuse coarctation of thoracoabdominal
      aorta associated with bilateral renal artery stenosis was demonstrated clearly by
      multidetector CT angiography. This is the first case of atypical aortic
      coarctation diagnosed by MDCTA.

PMID- 17033731
TI  - DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a
      single-nucleotide polymorphism microarray: standardization of molecular
      investigations of genetic diseases due to consanguinity.
AB  - Malignant osteopetrosis, a severe disease causing early infantile death in
      humans, is caused by mutations in the TCIRG1, CLCN7, or OSTM1 genes. We have
      established the molecular basis of malignant osteopetrosis in a Chinese family by
      means of whole-genome scans based on high-density single-nucleotide polymorphism
      (SNP) microarrays. Because the parents were consanguineous, the disease-causing
      locus should be located in an autozygous chromosomal region. Mapping revealed
      that among the three possible causal loci, only the CLCN7 gene was located in an
      autozygous region. Mutational analysis of the CLCN7 gene showed that the proband
      was homozygous for a novel missense mutation, p.I261F. p.I261 is located in helix
      F of the chloride channel, near a critical site for gating of the channel. This
      mapping study prepares the ground for future mutation studies by decreasing the
      burden of completely sequencing all possible loci for this disease. This approach
      can be used to standardize molecular investigations of genetic diseases due to
      consanguinity to a whole-genome scan and subsequent sequencing of the mapped
      disease gene.

PMID- 17033732
TI  - Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts
      identified through biological filtering of expression profiles.
AB  - Hutchinson-Gilford progeria syndrome (HGPS; MIM 176670) is a rare disease
      characterized by accelerated aging. In this study, light and immunofluorescence
      microscopy were used to assess morphological changes, measures of cell growth
      kinetics and gene expression profiles in HGPS cells and normal fibroblasts in
      culture. A filtering strategy was developed based on differentially expressed
      transcripts seen consistently across three culture stages based on cell passage
      number. This filtering strategy produced a list of 66 unique differentially
      expressed genes, of which approximately 40% were upregulated in HGPS cells
      compared to normal fibroblasts. The increased mRNA expression in HGPS cells that
      was seen for one gene defined using this strategy--namely ANK3--was validated
      using quantitative reverse-transcriptase amplification, Western analysis and
      immunofluorescence microscopy, all of which showed significantly increased
      ankyrin G expression. These findings demonstrate differences in morphology,
      growth kinetics and mRNA expression profiles in HGPS cells compared to normal
      fibroblasts in culture, including increased expression of ANK3/ankyrin G.
      Furthermore, other genes that co-clustered with ANK3 might provide mechanistic
      clues regarding senescence in cultured HGPS cells.

PMID- 17033733
TI  - Gene cloning and expression in Escherichia coli of a bi-functional beta-D
      xylosidase/alpha-L-arabinosidase from Sulfolobus solfataricus involved in xylan
      degradation.
AB  - An open reading frame encoding a putative bi-functional beta-D-xylosidase/alpha-L
      arabinosidase (Sso3032) was identified on the genome sequence of Sulfolobus
      solfataricus P2, the predicted gene product showing high amino-acid sequence
      similarity to bacterial and eukaryal individual beta-D-xylosidases and alpha-L
      arabinosidases as well as bi-functional enzymes such as the protein from
      Thermoanaerobacter ethanolicus and barley. The sequence was PCR amplified from
      genomic DNA of S. solfataricus P2 and heterologous gene expression obtained in
      Escherichia coli, under optimal conditions for overproduction. Specific assays
      performed at 75 degrees C revealed the presence in the transformed E. coli cell
      extracts of this archaeal activity involved in sugar hydrolysis and specific for
      both substrates. The recombinant protein was purified by thermal precipitation of
      the host proteins and ethanol fractionation and other properties, such as high
      thermal activity and thermostability could be determined. The protein showed a
      homo-tetrameric structure with a subunit of molecular mass of 82.0 kDa which was
      in perfect agreement with that deduced from the cloned gene. Northern blot
      analysis of the xarS gene indicates that it is specifically induced by xylan and
      repressed by monosaccharides like D-glucose and L-arabinose.

PMID- 17033735
TI  - Radiologic anatomy of the superior mesenteric vein and branching patterns of the
      first jejunal trunk: evaluation using multi-detector row CT venography.
AB  - The purpose of this study was to describe radiologic anatomy of the superior
      mesenteric vein (SMV) and to evaluate branching patterns of the first jejunal
      trunk on axial CT images and multi-detector row CT (MDCT) venography in adults.
      Two hundred and twenty consecutive patients who underwent abdominal CT
      examinations were enrolled in this study. Appearance of the SMV, branching
      patterns of the first jejunal trunk, and drainage site of the inferior mesenteric
      vein (IMV) were assessed on axial CT images and MDCT venography. The SMV and
      first jejunal trunk were identified in all patients. A single trunk of the SMV
      was present in 95% (210/220) and absent in 5% (10/220). First jejunal trunk
      crossed dorsal to the superior mesenteric artery (SMA) towards the left abdomen
      in 64% (141/220) and first jejunal trunk crossed ventral to the SMA in 19%
      (41/220). First jejunal trunk crossed dorsal to the SMA and abruptly turned
      towards the right abdomen in 17% (38/220). Among these 38 patients, biliary
      enteric bypass surgery (n = 9) and large hematoma in left abdomen (n = 1) were
      present. The IMV was identified in 213 patients and was observed to drain into
      splenic vein in 112 patients (53%), SMV in 67 (31%), splenoportal confluence in
      26 (12%), and first jejunal trunk in 8 (4%). In conclusion, the first jejunal
      trunk, abruptly turning toward the right abdomen, may be an anatomic variant or
      indirect finding of biliary-enteric anastomosis. The IMV may drain into the first
      jejunal trunk as well as splenic vein, splenoportal confluence, and SMV.

PMID- 17033734
TI  - Human pelvic extramural ganglion cells: a semiquantitative and
      immunohistochemical study.
AB  - In pelvic surgery, much attention is paid to nerve bundles but not to ganglion
      cells. Using serial section histology of 14 postmortem-treated hemipelvis (eight
      males, six females; mean, 79 years old), we examined the population number,
      distribution, and tyrosine hydroxylase-immunoreactivity (TH-IR; suggesting
      sympathetic neurons) of extramural pelvic ganglion cells. All pelvic ganglion
      cells were uniformly sized (25-30 microm) contrasting with small intramural
      rectal neurons. Abundant ganglion cells (30,000-140,000 unilaterally) existed not
      only along the pelvic viscera except for the rectum, but also along the
      hypogastric nerve, pelvic splanchnic nerve, pelvic plexus, and associated
      branches excluding those within the mesorectum. The intrapelvic ganglion cells
      outside the sympathetic trunk did not form macroscopically identifiable ganglia,
      but made small clusters (0.1-2.0 mm of maximum diameter) or were diffusely
      scattered within nerve bundles. More than half of these cells appeared TH-IR
      positive, although the positive/negative proportion differed between nerves and
      specimens. Greater numbers of ganglion cells were found in dorsosuperior sites
      (e.g., around the seminal vesicle) rather than in ventroinferior sites (e.g.,
      along the urethra) in males, and vice versa in females. However, in total cell
      numbers, interindividual variations were evident rather than intergender
      difference. Due to significant interindividual variations in cell number,
      differences are likely to exist between patients in "resistance" to surgical
      stresses. We hypothesized that pelvic ganglion cells are liable to be damaged due
      to drying along the surgical margin, hypoxia in venous bleeding, pressure from
      surgical retractors, extension stress with taping and excess traction and/or
      direct injury with electrical scalpels.

PMID- 17033736
TI  - CT differentiation of distal pancreas fat replacement and distal pancreas
      agenesis.
AB  - We aimed to describe CT signs useful for differentiation of distal agenesis from
      distal or dorsal pancreas lipomatosis. Multidetector CT (MDCT) studies of five
      patients with distal pancreas agenesis (n = 2), distal lipomatosis (n = 1),
      distal short pancreas (n = 1), and distal pancreatectomy (n = 1) were
      retrospectively reviewed. Agenesis of dorsal pancreas can be diagnosed by the
      absence of body and tail of pancreas. In the absence of distal pancreas, distal
      pancreatic bed can be filled by stomach or intestine (dependent stomach or
      dependent intestine signs), which abut splenic vein. Same findings can be seen in
      patients with distal pancreatectomy, however, splenic vein is absent in these
      patients. In case of distal lipomatosis abundant fat tissue is observed anterior
      to splenic vein. Dependent stomach and/or dependent intestine signs on MDCT
      imaging can allow differentiation of distal pancreas agenesis from distal
      lipomatosis obviating further diagnostic studies.

PMID- 17033737
TI  - Anxiety disorders among Nigerian women in late pregnancy: a controlled study.
AB  - This study aimed to investigate the rate and type of anxiety disorders among
      Nigerian women in late pregnancy. Women in late pregnancy (n = 172) and a non
      pregnant control group were assessed for DSM-IV anxiety disorders. The rate of
      any anxiety disorder in the pregnant women was 39.0% compared with 16.3% in the
      non-pregnant population (p < 0.001). Although all the anxiety disorders were more
      common, only the rate of social anxiety disorder was significantly higher among
      the pregnant than non-pregnant population. Correlates of anxiety disorder in the
      pregnant population include age less than 25 years (OR 4.62, 95% CI 2.39-8.92),
      primiparity (OR 3.90, 95% CI 2.00-7.59) and presence of medical conditions (OR
      3.60, 95% CI 1.28-10.12). More research is needed in this field to ascertain the
      specific association between pregnancy and anxiety disorders.

PMID- 17033738
TI  - Intimate partner violence and health outcomes in mid-life women: a population
      based cohort study.
AB  - AIM: To investigate the association between experience of intimate partner
      violence (IPV) and health outcomes measured prospectively. METHOD: Eleven-year
      prospective study of a population-based cohort of 438 Australian-born women aged
      45-55 years at baseline (in 1991). Annual face-to-face interviews measured health
      status and quality of life; questionnaires on intimate partner physical,
      emotional and sexual violence and on experiences of childhood abuse completed in
      year 6 of follow-up. RESULTS: In year 11 of follow-up 233 women (mean age 59.9 SD
      2.5 years) were interviewed of whom 62 (27%) reported experiencing physical
      and/or emotional and/or sexual IPV prior to the 6(th) year of follow-up. In bi
      variate analysis a history of IPV was significantly associated with mental and
      sexual health variables and marital status at baseline and follow-up.
      Multivariate analysis found that at follow-up after allowing for baseline
      measures and other co-variates: Frequency of Sexual Activities was lower in women
      who had experienced IPV (p < 0.05); and negative mood was higher in women with
      the experience of IPV during the 12 months prior to completing the violence
      questionnaire (p < 0.05). CONCLUSION: IPV was a significant contributor to mental
      and sexual health status measured prospectively in this cohort of mid-aged
      Australian-born women.

PMID- 17033739
TI  - Prevalence and psychosocial correlates of depressed mood during pregnancy and
      after childbirth in a Moroccan sample.
AB  - The objective of the current study was to determine the prevalence of depression
      among 100 women followed from the first trimester of pregnancy to 9 months after
      delivery. Mini International Neuropsychiatric Interview, Edinburgh Postnatal
      Depression Scale and Paykel Life Events Inventory were used. Seventeen per cent
      of the subjects experienced depression during postpartum, 19.2% started their
      episode during pregnancy. Psychosocial variables were positively correlated to
      depression during pregnancy.

PMID- 17033740
TI  - Does maternal psychopathology discriminate between children with DSM-IV
      generalised anxiety disorder or oppositional defiant disorder? The predictive
      validity of maternal axis I and axis II psychopathology.
AB  - What dimensions of maternal psychopathology predict internalising or
      externalising disorder in children? We conducted a study of maternal axis I and
      axis II psychopathology in a group of children 8-12 years of age with Generalised
      Anxiety Disorder (GAD), Oppositional Defiant Disorder (ODD) and non-patient
      controls (NC). By using Multigroup Discriminant Analyses (MDA) on three groups of
      children (N = 85) and measures of axis I and axis II psychopathology of their
      mothers, we attempted to discriminate between these groups on a data driven
      basis. Two separate MDA were computed, one based on maternal axis I disorders,
      and one based on maternal axis II disorders. The results demonstrated that
      maternal symptomatic and personality psychopathology was differentially related
      to childhood anxiety or behavioural disorders. Mothers of children with ODD were
      characterised by more negative emotions and detached personality styles, whereas
      mothers of children with GAD seemed to be more somatic preoccupied, controlling
      and over-protective.

PMID- 17033741
TI  - Cellular and matrix mechanics of bioartificial tissues during continuous cyclic
      stretch.
AB  - Bioartificial tissues are useful model systems for studying cell and extra
      cellular matrix mechanics. These tissues provide a 3D environment for cells and
      allow tissue components to be easily modified and quantified. In this study, we
      fabricated bioartificial tissue rings from a 1 ml solution containing one million
      cardiac fibroblasts and 1 mg collagen. After 8 days, rings compacted to <1% of
      original volume and cell number increased 2.4 fold. We initiated continuous
      cyclic stretching of the rings after 2, 4, or 8 days of incubation, while
      monitoring the tissue forces. Peak tissue force during each cycle decreased
      rapidly after initiating stretch, followed by further slow decline. We added 2
      microM Cytochalasin-D to some rings prior to initiation of stretch to determine
      the force contributed by the matrix. Cell force was estimated by subtracting
      matrix force from tissue force. After 12 h, matrix force-strain curves were
      highly nonlinear. Cell force-strain curves were linear during loading and showed
      hysteresis indicating viscoelastic behavior. Cell stiffness increased with
      stretching frequency from 0.001-0.25 Hz. Cell stiffness decreased with stretch
      amplitude (5-25%) at 0.1 Hz. The trends in cell stiffness do not fit simple
      viscoelastic models previously proposed, and suggest possible strain-amplitude
      related changes during cyclic stretch.

PMID- 17033742
TI  - Low-level laser therapy can reduce lipopolysaccharide-induced contractile force
      dysfunction and TNF-alpha levels in rat diaphragm muscle.
AB  - Our objective was to investigate if low-level laser therapy (LLLT) could improve
      respiratory function and inhibit tumor necrosis factor (TNF-alpha) release into
      the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide
      (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS
      injection, and LPS groups receiving either (a) no therapy, (b) four sessions in
      24 h with diode Ga-AsI-Al laser of 650 nm and a total dose of 5.2 J/cm2, or (c)
      an intravenous injection (1.25 mg/kg) of the TNF-alpha inhibitor chlorpromazine
      (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm
      muscle from 24.15+/-0.87 N in controls, but the addition of LLLT partly inhibited
      this reduction (LPS only: 15.01+/-1.1 N vs LPS+LLLT: 18.84+/-0.73 N, P<0.05). In
      addition, this dose of LLLT and CPZ significantly (P<0.05 and P<0.01,
      respectively) reduced TNF-alpha concentrations in diaphragm muscle when compared
      to the untreated control group.

PMID- 17033743
TI  - An evaluation of the effect of a gastric ischemia-reperfusion model with laser
      Doppler blood perfusion imaging.
AB  - The objectives of this study are to establish a gastric ischemia-reperfusion
      model and test it using the laser Doppler blood perfusion imaging (LDPI) method
      and to evaluate the role of the LDPI technique in the measure of gastric blood
      circulation. The right gastric artery of the rat was clamped for 30 min and then
      reperfused. The LDPI was used to display the blood circulation of the whole
      gastric surface during this process. The blood flow perfusion image of the
      gastric surface was displayed clearly. After the right gastric artery was
      clamped, the blood flow perfusion on the gastric surface decreased very
      significantly until the clamp was loosened. Following reperfusion, the blood flow
      suddenly increased. Within the first 10 min, the blood-flow perfusion exceeded
      the level before the clamping and then gradually became smooth and steady. The
      right gastric artery is a main pathway for gastric blood supply. LDPI can display
      successfully the blood circulation state of the stomach and the course of
      ischemia-reperfusion of a large area with an image.

PMID- 17033745
TI  - Five years after 9/11-fearing smallpox, ... and the vaccine against it.

PMID- 17033746
TI  - Estimation of the duration of vaccine-induced residual protection against severe
      and fatal smallpox based on secondary vaccination failure.
AB  - BACKGROUND: Understanding the loss of vaccine-induced immunity against smallpox
      is essential in determining the fraction of those who are still protected in the
      present population and in constructing effective countermeasures against
      bioterrorist attacks. METHOD: Three small Australian outbreaks from the 1880s to
      early 1900s were investigated. Each documented individual age at infection. The
      case records for Launceston, 1903, further documented the age at vaccination and
      disease severity, enabling estimates of the duration of protection against severe
      and fatal smallpox. RESULTS: A significant association between vaccination and
      death was observed in the outbreak in Sydney, 1881 (odds ratio of death among
      vaccinated individuals = 0.3; 95% confidence interval (CI): 0.1, 0.8; p = 0.02),
      where the time since last vaccination was similar for all vaccinated cases. In
      Launceston, 1903, where the age at vaccination varied widely, the median duration
      of partial protection against severe and fatal smallpox was estimated to be 31.7
      (95% CI: 13.2, 116.2) and 53.9 (95% CI: 25.6, 123.5) years after vaccination,
      respectively. Whereas those in their 20s are expected to have the highest
      frequency of vulnerability to smallpox death in the present population,
      infections among those in their 30s or 40s are expected to be much less fatal.
      CONCLUSION: Long lasting partial protection was suggested from the outbreak
      records, the estimated durations of which were roughly consistent with those
      reported previously. In the event of a bioterrorist attack, those involved in
      emergency tasks before emergency vaccination practices are re-established should
      ideally be previously vaccinated individuals in their 30s or 40s.

PMID- 17033747
TI  - Postneurosurgical nosocomial bacterial brain abscess in adults.
AB  - BACKGROUND: Bacterial brain abscess after a neurosurgical procedure has become an
      important occurrence in the hospital setting. However, no information about the
      frequency, clinical relevance, and the outcome has been reported. PATIENTS AND
      METHODS: Over a period of 19 years (1986- 2004), a total of 31 patients were
      retrospectively identified as having brain abscesses after neurosurgical
      procedures and were enrolled in this study. RESULTS: Those included in this study
      accounted for 0.17% (31/18600) of all neurosurgical procedures in the same
      period. There was an increased percentage of adult postneurological nosocomial
      brain abscess compared to all adult bacterial brain abscesses in recent years.
      The majority of cases were due to Gram-negative bacilli and polymicrobial
      infections, including both Gram-negative bacilli and Staphylococcus species.
      Furthermore, the appearance of multi-antibiotic resistant strains was also noted
      during the study period. The overall fatality rate was 16%. CONCLUSION: Post
      neurosurgical states have become important predisposing factor for bacterial
      brain abscess. In patients that undergo neurosurgical procedures and develop
      smoldering fever, progressively disturbed consciousness, headache, and new onset
      focal neurologic signs, immediate neuro-imaging studies should be undertaken to
      determine whether bacterial brain abscess is present. Although mortality may be
      related to the primary brain pathology, early diagnosis and timely use of
      appropriate antibiotics based on antimicrobial susceptibility testing are also
      essential for survival.

PMID- 17033748
TI  - Enterobacter bacteremia: Clinical features, risk factors for multiresistance and
      mortality in a Chinese University Hospital.
AB  - BACKGROUND: This study was performed to characterize the clinical features and to
      identify the risk factors for multiresistance and mortality in patients with
      Enterobacter bacteremia. PATIENTS AND METHODS: A number of 126 patients with
      Enterobacter bacteremia in 1995-2004 at the Medical university-affiliated
      Hospital of Anhui, China were retrospectively analyzed. RESULTS: Of the 126 cases
      of bacteremia, 81 (64.3%) patients were identified as nosocomial infection. The
      overall multiresistance rate was 45.2% (57/126). Multiresistance was associated
      with nosocomial infection, recent invasive procedure, previous third-generation
      cephalosporins therapy, prolonged perioperative prophylaxis, the species of
      Enterobacter (E. cloacae) and polymicrobial bacteremia in univariate analysis. In
      multivariate analysis, previous third-generation cephalosporins therapy (OR =
      13.6, p = 0.007) and prolonged perioperative prophylaxis (OR = 6.4, p = 0.029)
      were the strong, independent risk factors for the multiresistance. The crude 30
      day mortality rate was 39.7% (50/126). Mortality directly attributed to
      Enterobacter spp. was 32.5% (41/126), which was significantly associated with
      multiresistance, nosocomial infection, recent invasive procedure, and
      inadequately empirical therapy in univariate analysis. Multivariate analysis
      revealed that only nosocomial infection (OR = 3.292, p = 0.049) was independently
      associated with mortality. The survival curve showed that the inappropriate
      initial therapy group had a lower probability of survival than the appropriate
      therapy group in infection-related mortality (Log Rank, p = 0.0142). CONCLUSION:
      Enterobacter is becoming increasingly important nosocomial pathogens. Nosocomial
      infection is a clinical risk factor tightly associated with multiresistance and
      worse outcome. More judicious use of third-generation cephalosporins may decrease
      the incidence of nosocomial multiresistant Enterobacter spp. in China.

PMID- 17033749
TI  - Influence of prolonged use of intravenous administration sets in paediatric
      cancer patients on CVAD-related bloodstream infection rates and hospital
      resources.
AB  - BACKGROUND: To assess the effects of extending the routine intravenous
      administration set (IVAS) change-interval from 72 h (group 1) to 7 days (group 2)
      on the incidence density for central venous access device (CVAD)-related
      bloodstream infections (BSIs) and on resource expenditures in a singlecentre
      pilot study. PROCEDURE: Prospective pre-/post-intervention comparison of two
      consecutive 12-month surveillance periods (2001-2003) in a 17-bed paediatric
      oncology tertiary care unit. IVAS changes and nosocomial infections (NIs) were
      prospectively analysed using a standardized unit-based surveillance system
      (Oncopaed NI). RESULTS: All 175 eligible patients were enrolled, 96 in group 1
      and 79 in group 2. Both groups had similar distributions of primary diagnoses and
      risk factors. The proportion of IVAS changes performed after 3 days increased
      from 5.6% to 22.5%, but only 8% of IVASs in group 2 were changed after 7 days.
      Most IVAS changes (64.8% in group 1 and 92.9% in group 2) were done because of
      therapeutic interventions (blood products, parenteral nutrition [TNP]) before the
      scheduled endpoint. Overall, the rates and incidence densities of NIs were
      significantly lower during the second period. The corresponding results for CVAD
      related BSIs did not show significant differences. No death attributable to a NI
      occurred. The '7-day' strategy resulted in cost savings for devices (3,300
      dollars/year) and of nursing time (23 working days/year). CONCLUSIONS: Extending
      the routine IVAS change-interval from 3 days to 7 days appears to be safe and
      cost-effective in a paediatric oncology unit with high infection control
      standards and continuous surveillance for NIs. These results do not prove that 7
      day intervals prevent infections, but they do suggest that this policy probably
      is not harmful and that a prospectively randomized study with sufficient power is
      needed.

PMID- 17033750
TI  - Detection of legionella species in clinical samples: Comparison of polymerase
      chain reaction and urinary antigen detection kits.
AB  - BACKGROUND: Recently, two excellent methods have been used for the diagnosis of
      Legionnaires' disease: urinary antigen detection and PCR. The purpose of the
      present study is to analyze and evaluate the sensitivity and specificity of three
      different urinary antigen detection kits as well as PCR. MATERIALS AND METHODS: A
      total of 148 samples were collected from 33 patients between 1993 and 2004. These
      consisted of 73 urine samples obtained from 33 patients, 57 serum samples
      provided by 29 patients, and 18 respiratory tract specimens from 13 patients.
      Three commercially available kits were used to detect urinary antigen. For the 5S
      PCR reaction, primers L5SL2 and L5SR84 were used. RESULTS: Positive results were
      shown in all patients' urine (representing 79.5% of total samples) using the
      Binax EIA kit, in 93.9% patients (representing 75.3% samples) using the Binax NOW
      immunochromatographic kit, and in 90.9% (representing 72.6% samples) using the
      Biotest EIA kit. Urine samples from 12.1% patients (representing 6.8% of total
      samples), serum samples from 41.4% patients (representing 35.1% of total
      samples), and respiratory samples from 84.6% patients (representing 88.9% of
      total samples) showed positive results with PCR. CONCLUSION: In testing urine of
      legionellosis patients, it was suggested that three kits were all valuable tools
      for diagnosis of legionellosis. Since over one-third of patients' serum samples
      and most respiratory specimens showed positive results with PCR, the addition of
      PCR for testing of these samples might be useful, particularly in cases of
      culture negative and serum antibody negative patients.

PMID- 17033751
TI  - Regional variation in outpatient antibiotic prescribing in Germany.
AB  - OBJECTIVE: According to recent surveys, outpatient antibiotic prescribing in
      Germany has been comparatively low among European countries. We assessed regional
      variation in outpatient antibiotic use within Germany both for overall use as
      well as for specific antibiotic drug classes. METHODS: Prescription data for the
      year 2003 covering approximately 90% of the total population were analysed using
      the ATC/WHO defined daily dose (DDD) methodology. Data were expressed in DDD per
      1,000 persons covered by the insurance and day (DID). RESULTS: Outpatient
      antibiotic prescribing in 2003 was 13.6 DID and ranged between 9.2 and 17.9 DID
      in the different regions examined. Low consumption regions were eastern and
      southern states. High consumption areas were in the west near the French and
      Belgian border. This regional prescribing pattern was similar for children and
      adults. Penicillins were the most frequent prescribed drugs, but their use
      density showed a relatively large regional variation (factor 3.5), with
      relatively low prescription frequency in the eastern states. In almost all
      regions quinolones were used more often than trimethoprim-sulfamethoxazole.
      CONCLUSION: The regional variation in recent outpatient antibiotic prescribing in
      Germany is substantial. The relatively high antibiotic use in the western part of
      the country is remarkable, remains unexplained and requires further study.

PMID- 17033752
TI  - Is there significant regional variation in hospital antibiotic consumption in
      Germany?
AB  - OBJECTIVE: Outpatient antibiotic use in Germany differs substantially between
      eastern and southern parts of the country (low use) and the western part (high
      use). Whether similar regional variation exists in hospital antibiotic
      consumption is not known. We investigated this issue using a convenience sample
      of 145 hospitals providing data for the year 2003. METHODS: Data on hospital
      consumption of systemic antibiotics in Anatomical Therapeutic Chemical (ATC)
      class J01 were obtained from acute care hospitals that participated in an IMS
      survey and had complete data (dispensed drugs and patient-days per year) for at
      least one non-pediatric, non-psychiatric department or ward. A total of 275 non
      ICU surgical departments/wards, 229 non-ICU non-surgical (general medicine,
      haematology-oncology, neurology/stroke) departments/wards, and 184 ICUs were
      analysed. Data were expressed in DDD (WHO/ATC definition version 2003) or daily
      doses adapted for recommendations in hospitalized patients (RDD) per 100 patient
      days (DDD/100 and RDD/100). FINDINGS: The weighted mean over all
      departments/wards was 49.6 DDD/100 or 31.3 RDD/100, respectively. As expected,
      ICU antibiotic use density was much higher than use in non-ICU areas, and use in
      haematology-oncology was higher than in other non-surgical departments/wards. In
      univariate analyses, region, hospital bed-size category, university affiliation
      and haematology-oncology as specialty were associated with use density, but these
      associations were only partly confirmed in multivariate logistic regression
      analyses of factors associated with excess (> or = 75%) use density which showed
      university affiliation and haematology-oncology but not hospital location to be
      independently associated with comparatively high use. CONCLUSIONS: Antibiotic use
      density in German acute care hospitals does not appear to differ significantly
      between regions. Overall hospital consumption of antibiotics in this country
      appears to be similar to what has been described from other parts of Europe. In
      comparative analyses of hospital antibiotic consumption, data need to be adjusted
      at least for university affiliation and haematology-oncology.

PMID- 17033753
TI  - Epidemiology and clinical characteristics of patients with Staphylococcus
      saprophyticus bacteriuria in Israel.
AB  - BACKGROUND: Staphylococcus saprophyticus is a leading cause of lower urinary
      tract infections (UTI) in young women in the USA, Canada and Scandinavian
      countries, but seems to be very rare in other countries like Israel. The goal of
      this study was to investigate the incidence of S. saprophyticus in Northern
      Israel and to compare demographic and clinical characteristics of patients with
      S. saprophyticus and Escherichia coli bacteriuria. PATIENTS AND METHODS: Data
      from all patients with S. saprophyticus bacteriuria isolated in two major
      laboratories in northern Israel during a 1-year period were analyzed and clinical
      and epidemiological findings from 129 patients with S. saprophyticus bacteriuria
      were compared to that of 129 patients with E. coli bacteriuria. RESULTS: The
      incidence of S. saprophyticus in our region was 0.09% among all urine cultures
      requested. Patients with S. saprophyticus bacteriuria are mainly young women,
      more likely suffering asymptomatic bacteriuria, complain less of dysuria and
      burning and are less hospitalized than those infected with E. coli. Reported risk
      factors associated to S. saprophyticus bacteriuria such us seasonal variation,
      occupation in meat products industry, use of contraceptives, or sexual activity
      were not found by us. No nasal, vaginal, or rectal carriage was demonstrated.
      CONCLUSION: S. saprophyticus is a very uncommon urinary pathogen in Northern
      Israel. The natural reservoir of this uropathogen in our region remains unknown.

PMID- 17033754
TI  - Severe reactivation of hepatitis B virus infection in a patient with hairy cell
      leukemia: Should lamivudine prophylaxis be recommended to HBsAg-negative, anti
      HBc-positive patients?
AB  - The reverse seroconversion to hepatitis B virus infection has been sporadically
      described in onco-haematological patients receiving cytotoxic therapy or
      allogeneic bone marrow transplantation and can be associated with the development
      of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive
      patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year
      after the last course of 2-CdA and 6 months after splenectomy, while the patient
      was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to
      lamivudine therapy followed by viral clearance.

PMID- 17033755
TI  - Endogenous endophthalmitis with azole-resistant Candida albicans--Case report and
      review of the literature.
AB  - Candida endophthalmitis accounts for the majority of fungal endophthalmitis.
      Despite its clinical relevance there are no controlled trials on different
      treatment regimens. We report a case of endogenous endophthalmitis caused by
      azole-resistant Candida albicans following abdominal surgery in an otherwise
      healthy woman, and review the literature concerning treatment recommendations. In
      consideration of the serious outcome with loss of sight in insufficiently treated
      endophthalmitis we like to increase awareness to this disease entity and the
      possibility of azole-resistance, even in treatment-naive patients.

PMID- 17033756
TI  - Evidence of coinfection with distinct strains of Burkholderia multivorans in a
      cystic fibrosis patient.
AB  - We report a Cystic Fibrosis patient with chronic Burkholderia multivorans
      infection involving persistency of one strain and temporary, consecutive
      coinfection with two different strains. Comparison of the colony morphology with
      the genotype revealed no correlation. These data are important for interpretation
      of clinical outcome and transmission studies in CF patients.

PMID- 17033757
TI  - Linezolid therapy of bloodborne teicoplanin-resistant Staphylococcus
      haemolyticus.

PMID- 17033758
TI  - Clinical news from the XVI International AIDS Conference: The attempt of a
      summing up.
AB  - Topics highlighted at the XVI International AIDS Conference in Toronto included
      HIV/AIDS vaccine research, entry inhibitors, integrase inhibitors, new NNRTIs and
      PIs, single-agent therapies, pre-exposure prophylaxis and microbicides. Beside
      the large scientific part, policy and funding were of great concern. Within this
      article we are trying to focus on topics with direct clinical relevance. This
      includes new epidemiological and resistance data, results from current studies
      investigating established and novel antiretroviral drugs and drug classes as well
      as new findings in therapy management and strategies.

PMID- 17033759
TI  - Is ACL reconstruction only for athletes? A study of the incidence of meniscal and
      cartilage injuries in an ACL-deficient athlete and non-athlete population: an
      Indian experience.
AB  - While anterior cruciate ligament (ACL) reconstruction is readily offered to
      athletes, non-athletes are often treated conservatively. We carried out a
      retrospective, cross-sectional analysis study to compare the incidence of
      meniscal and cartilage injuries in an athlete and non-athlete population in
      relation to time of presentation since injury. The results were used to assess
      the need and relevance of ACL reconstruction in the non-athlete population. The
      study included 1375 patients who underwent ACL reconstruction between 1998 and
      2004. These patients were initially broadly divided into two categories: athletes
      (575) and non-athletes (800). Each category was then sub-divided into four
      subgroups based on time elapsed between the injury and presentation at our clinic
      (Group A, 3 months; Group B, 3-12 months; Group C, 1-3 years; Group D, more than
      3 years). Arthroscopic findings were documented for medial and lateral meniscus
      and cartilage injuries, and comparisons were made between the incidence of
      associated injuries in the corresponding groups. There was a statistically
      significant increase in the incidence of meniscal injuries and cartilage injuries
      after 1 year in both the groups. There was no difference in the incidence of
      meniscal and cartilage injuries in athletes and non-athletes among the
      corresponding groups. (chi-square test, p = 0.05). These results demonstrate that
      both athletes and non-athletes are equally susceptible for long-term meniscal and
      cartilage injuries if ACL reconstruction is not carried out early.

PMID- 17033761
TI  - Incidence of hip fracture in southeastern Norway: a study of 1,730 cervical and
      trochanteric fractures.
AB  - The incidence of hip fracture has been studied extensively, but there is still
      some doubt whether the age-specific incidence is increasing. The proportion of
      trochanteric fractures has varied and has also been said to be increasing. We
      studied data on 1,730 prospectively registered cases from 1998-2003 and computed
      age- and gender-specific incidence rates for intracapsular and trochanteric
      fractures. The incidence of hip fracture for women over 50 years was 1,263 and
      for men 452 per 100,000. The proportion of trochanteric fractures was 38% for
      women and 41% for men. There was no significant difference in the proportion of
      trochanteric fractures either between or within the genders, and the proportion
      did not exceed 50% in any age group. These findings confirm the high incidence of
      hip fracture in Norway but do not indicate any increase. The proportion of
      trochanteric fractures also seems to be stable.

PMID- 17033762
TI  - Evaluation of complications of three different types of proximal extra-articular
      femur fractures: differences in complications, age, sex and surviving rates.
AB  - The comparability of studies of extra-articular proximal femur fractures is
      compromised by the lack of a widely accepted, simple classification system with
      clinical and prognostic relevance. The aim of the study is to define the
      complication profile as well as differences relating to age, gender and survival
      rate of simple trochanteric fractures, intertrochanteric comminuted and
      subtrochanteric fractures. Records of 335 consecutive patients were analysed.
      Patients had a median follow-up of 10 (1-56) months, and were treated operatively
      with three intramedullary nailing systems. Simple trochanteric fractures (n=67)
      show wound healing problems (1.5%). Median age is m/f 77(45-98) years/ 85(39
      101), and two-year survival rate is m/f 50.3%/ 84.9%. Intertrochanteric
      comminuted fractures (n=204) show the highest complications (25%), 9.7%
      femoralhead perforations, 3.5% hardware related problems and 11.8% wound healing
      problems. Median age is m/f 75(41-94) years/ 85(54-100), survival rate is m/f
      92.7%/ 66.5%. Complication rate is 17.0% in subtrochanteric fractures (n=64), no
      femoralhead perforation but 9.1% other hardware problems and 7.8% wound healing
      problems. Median age is m/f 72(24-91) years/ 83(38-99), survival rate is m/f
      92.3%/ 67.9%. Females show higher complication rates compared to males (19%
      versus 10%). The three types of fractures show different patterns of
      complications, survival rates, age, and sex distribution.

PMID- 17033763
TI  - Are drains required following a routine primary total joint arthroplasty?
AB  - The purpose of this study was to evaluate the benefits of suction drainage
      following primary total joint arthroplasty. We reviewed primary total hip and
      knee replacements separately and together in 126 consecutive patients. There were
      63 patients each in the drainage and no drainage groups. Sex distribution and
      anticoagulant use were similar in the two groups. All patients underwent the same
      operative technique and method of closure. The mean postoperative fall in
      haemoglobin was 3.2 and 3.3 gm/dl in the drainage and no drainage groups
      respectively. There was no statistically significant difference between the two
      groups with regard to blood transfusion requirements, rehabilitation time,
      postoperative complications such as hypotension and wound infections (p>0.05).
      The average rehabilitation time in both groups was 8-9 days. The routine use of a
      suction drain is unnecessary after an uncomplicated total joint arthroplasty.

PMID- 17033764
TI  - Surgical treatment of undisplaced femoral neck fractures in the elderly.
AB  - The study was a retrospective evaluation and comparison. Eighty-four elderly
      patients (> 60 years) with undisplaced intracapsular femoral neck fractures were
      treated with osteosynthesis with either dynamic hip screws (DHS) or multiple
      cannulated screws (MCS). The Singh index was used to evaluate bone quality. All
      patients were followed up retrospectively for at least 12 months. The clinical
      results were compared between the DHS and MCS groups. Both groups were similar in
      respect of injury mechanisms, mean Singh index, injury-surgery interval, gender
      and age (all p values > or = 0.29). The MCS group had significantly smaller wound
      incisions, less haemoglobin level drops, lower blood transfusion rates and
      shorter hospital stays than the DHS group (all p values < or = 0.008). However,
      the DHS group had a higher rate of overall success when compared to the MCS group
      (97.5% versus 84.1%, p=0.04). In conclusion, although DHS fixation requires a
      larger skin incision and more soft tissue dissection, its use in elderly patients
      with osteoporosis is recommended due to simple, efficacy and high overall success
      rate.

PMID- 17033765
TI  - Minimally invasive plate osteosynthesis in the treatment of proximal humeral
      fracture.
AB  - The management of fractures of the proximal shaft of the humerus has been
      evolving since the development of new techniques and new implants in recent
      years. It seems that this kind of fracture has an increasing incidence in the
      older, osteoporotic population. In the last 2 years, we have operated on 17
      patients, with an average age of 65, who had proximal humeral shaft fractures
      treated by minimally invasive percutaneous osteosynthesis (MIPO) technique using
      the metaphyseal locking compression plate. Our study evaluated the surgical
      technique used and the outcome for these patients with regards to their range of
      movement and shoulder function. Our results showed that all the patients could
      achieve at least 140 masculine of shoulder abduction in the first 6 months after
      the operation, except for three patients who had shoulder impingement. These
      patients had an average Constant score of 76.8. All fractures had bony union at 6
      months, except one, which was probably due to poor reduction in the initial
      operation. Another complication that we encountered was radial nerve neuropraxia.
      The ways to prevent these complications are discussed. In conclusion, MIPO
      fixation using the metaphyseal locking compression plate is a good option for the
      management of proximal humeral shaft fractures. It provides early functional
      recovery, but we had to pay special attention to some of the surgical details in
      order to minimise complications.

PMID- 17033766
TI  - Tension-band wiring of transverse fractures of patella. The effect of site of
      wire twists and orientation of stainless steel wire loop: a biomechanical
      investigation.
AB  - Tension-band wiring is commonly used to treat transverse patella fractures. The
      most common configuration has parallel Kirschner (K) wires and a stainless steel
      wire loop placed in a vertically oriented figure of eight. Early mobilisation is
      important but can cause detrimental displacement at the fracture site. A wooden
      model of a transversely fractured patella was used to compare different fixation
      constructs. The fracture was fixed using two K wires and a stainless steel wire
      loop. One or two wire twists were used, placed either arbitrarily or at corners
      of the loop. The loop was oriented either vertically or horizontally.
      Interfragmentary compression at the point of wire breakage and permanent
      displacement on cyclic loading was measured for each construct. Placement of the
      figure of eight in a horizontal orientation with two wire twists at the corner
      improved interfragmentary compression by 63% (p<0.05, Tukey post hoc test). On
      cyclic loading, all constructs with vertical figure of eight but none with a
      horizontal construct failed (p=0.01; Fisher's exact test). Permanent fracture
      displacement after cyclic loading was 67% lower with horizontal figure of eight
      constructs (p<0.05; t test). Placing wire twists at the corner and a horizontal
      placement of figure of eight improves stability of the construct.

PMID- 17033768
TI  - Near-infrared reflectance spectroscopy as a fast and non-destructive tool to
      predict foliar organic constituents of several woody species.
AB  - Near-infrared reflectance spectroscopy (NIRS) was used to estimate N, neutral
      detergent fibre (NDF), acid detergent fibre (ADF), lignin and cellulose contents
      in leaves of a heterogeneous group of 17 woody species from the Central Western
      region of the Iberian Peninsula. The sample set consisted of 182 samples of
      leaves of deciduous and evergreen species, showing a wide range of concentrations
      determined by reference methods: 6.60-35.2 g kg-1 (N), 15.5-66.0% (NDF), 10.2
      57.3% (ADF), 3.45-27.4% (lignin) and 5.79-31.3% (cellulose). Reflectance spectra,
      obtained for samples of dried and ground leaves, were recorded as log1/R
      (R=reflectance) from 1,100 to 2,500 nm. NIRS calibrations were developed using
      multiple linear (MLR) and partial least-squares (PLSR) regressions, and tested by
      external validation. Spectral data were transformed to the first and second
      derivative (1D, 2D). The PLSR method and derivative transformations provided the
      best statistics and showed lower standard errors of calibration (SEC) and higher
      coefficients of multiple determination (R2). In the external validation the
      standard errors of prediction (SEP) were 0.76 g kg-1 (N), 2.11% (NDF), 1.47%
      (ADF), 0.85% (lignin) and 0.86% (cellulose). The results obtained show that NIRS
      is very effective for the estimation of these organic constituents in leaf tissue
      of woody species. This technique can be used in ecological or ecophysiological
      studies as an alternative to the more time-consuming standard methods.

PMID- 17033769
TI  - Tagging of avidin immobilized beads with biotinylated YAG:Ce3+ nanocrystal
      phosphor.
AB  - YAG:Ce3+ nanoparticles 9.5+/-1.2 nm in diameter have been synthesized from
      aluminium isopropoxide and acetates of yttrium and cerium in 1,4-butanediol (1,4
      BD) by autoclave treatment at 300 degrees C for 2 h. After replacing 1,4-BD by
      ultrapure water, NH2 groups were introduced on the surface of YAG:Ce3+
      nanoparticles by addition of 3-aminopropyltrimethoxysilane then biotinylation
      with sulfo-NHS-LC-biotin. We demonstrated that avidin immobilized beads are
      tagged by biotinylated YAG:Ce3+ nanoparticles by the selective avidin-biotin
      interaction, furnishing a green fluorescent image on excitation with blue light.
      This result indicates that YAG:Ce3+ nanoparticle phosphors have much potential in
      biological applications.

PMID- 17033770
TI  - Characterization of the coupling of quantum dots and immunoglobulin antibodies.
AB  - Water-soluble quantum dots (QDs) were used to label goat anti-human
      immunoglobulin antibodies (Abs), and the labeling process was characterized by
      column purification. The QDs obtained in organic solvent were modified with
      mercaptoacetic acid (MAA) and became water-soluble. These water-soluble QDs were
      linked to the antibodies using the coupling reagents ethyl-3-(dimethyl
      aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The linking
      process was shown to be effective by ultra-filter centrifugation and column
      purification. After comparing the quantities of Abs and water-soluble QDs
      involved in the linking reaction via column purification, it was found that a
      molar Abs:QD ratio of >1.2 resulted in most of the water-soluble QDs becoming
      covalently linked to the Abs. The circular dichroism (CD) spectra of Abs and QD
      Ab conjugates were very similar to each other, indicating that the secondary
      structure of Abs remained largely intact after the conjugation. Finally, antigen
      (Ag)-antibody (Ab) recognition reactions perfomed on the surface of a glass slide
      showed that the conjugate retained the activity of Abs. This work lends support
      to the idea of linking biomolecules to QDs, and thus should aid the application
      of QDs to the life sciences.

PMID- 17033771
TI  - Labeling the human skeleton with 41Ca to assess changes in bone calcium
      metabolism.
AB  - Bone research is limited by the methods available for detecting changes in bone
      metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical
      markers are subject to significant intra-individual variation. In the study
      presented here, we evaluated the isotopic labeling of bone using 41Ca, a long
      lived radiotracer, as an alternative approach. After successful labeling of the
      skeleton, changes in the systematics of urinary 41Ca excretion are expected to
      directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi)
      was administered orally to 22 postmenopausal women. Kinetics of tracer excretion
      were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700
      days post-dosing using accelerator mass spectrometry and resonance ionization
      mass spectrometry. Isotopic labeling of the skeleton was evaluated by two
      different approaches: (i) urinary 41Ca data were fitted to an established
      function consisting of an exponential term and a power law term for each
      individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM)
      analysis to identify a compartmental model that describes urinary 41Ca tracer
      kinetics. A linear three-compartment model with a central compartment and two
      sequential peripheral compartments was found to best fit the 41Ca data. Fits
      based on the use of the combined exponential/power law function describing
      urinary tracer excretion showed substantially higher deviations between predicted
      and measured values than fits based on the compartmental modeling approach. By
      establishing the urinary 41Ca excretion pattern using data points up to day 500
      and extrapolating these curves up to day 700, it was found that the calculated
      41Ca/40Ca isotope ratios in urine were significantly lower than the observed
      41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome
      this limitation. By identifying relative changes in transfer rates between
      compartments in response to an intervention, inaccuracies in the underlying model
      cancel out. Changes in tracer distribution between compartments were modeled
      based on identified kinetic parameters. While changes in bone formation and
      resorption can, in principle, be assessed by monitoring urinary 41Ca excretion
      over the first few weeks post-dosing, assessment of an intervention effect is
      more reliable approximately 150 days post-dosing when excreted tracer originates
      mainly from bone.

PMID- 17033772
TI  - Single-molecule tracking in eukaryotic cell nuclei.

PMID- 17033773
TI  - A screening system for active and enantioselective amidase based on its acyl
      transfer activity.
AB  - A novel enantioselective amidase screening system was developed and proved to be
      efficient and accurate. This screening system employed acyl transfer activity of
      amidase in the presence of hydroxylamine, leading to the formation of hydroxamic
      acids, followed by spectrophotometric quantification of hydroxamic acid/iron(III)
      complexes. The enantioselectivities of amidase were evaluated by employing (R, S)
      2, 2-dimethyl cyclopropanecarboxamide (1), (S)-2, 2-dimethyl
      cyclopropanecarboxamide and their mixture as substrates concurrently under the
      same conditions. To prove the accuracy of the screening system,
      enantioselectivity of acyl transfer reaction (E (T)) and that of hydrolytic
      reaction (E (H)) was compared. With this method, we obtained eight microorganism
      strains with enantioselective amidase from 523 isolates, two of which showed R
      stereospecific avtivity for (R, S)-1.

PMID- 17033774
TI  - Early attack and subsequent changes produced in an industrial lignin by a fungal
      laccase and a laccase-mediator system: an analytical approach.
AB  - An industrial kraft pine lignin (Indulin AT, KL) was characterized and treated in
      both aqueous-buffered media and dioxane to water, either with a partially
      purified laccase from Fusarium proliferatum or with the laccase plus 2,2'-azino
      bis-3-ethylbenzothiazoline-6-sulfonic-acid (ABTS) as mediator. The changes in the
      lignin after different incubation periods were analyzed through the application
      of high performance liquid chromatography (HPLC), UV-visible (Vis) spectroscopy
      and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). At the onset of
      incubation, laccase-treated samples showed a slight polymerization and strong
      modifications in UV-Vis spectra. Through Py-GC/MS, a decrease in phenolic and
      methoxy-bearing pyrolysis products was observed, in contrast to an increase in
      the more oxidized products. After longer incubation periods (48 h) a substantial
      polymerization was detected by HPLC, along with a decrease in the guaiacyl (G)
      units. In contrast, the analysis by HPLC of the samples recovered from the
      laccase-ABTS system (LMS) showed an intense depolymerization, accompanied by a
      sizeable loss in G units and a decrease in the methyl and ethyl side-chain
      phenolic compounds. These results provide conclusive evidence of a rapid initial
      attack of the industrial lignin by laccase and notable modifications in the KL
      after longer incubation periods with laccase or LMS.

PMID- 17033775
TI  - Outdoor cultivation of lutein-rich cells of Muriellopsis sp. in open ponds.
AB  - The growth performance of the chlorophycean microalga Muriellopsis sp. outdoors
      in open tanks agitated with a paddlewheel and its ability to accumulate
      carotenoids have been evaluated throughout the year. The cells grown in the open
      system had free lutein as the main carotenoid, with violaxanthin, beta-carotene,
      and neoxanthin also present. Lutein content of the dry biomass ranged from 0.4 to
      0.6%, depending on the growth and environmental conditions. In addition, the
      biomass of Muriellopsis sp. had a high content in both protein and lipids with
      about half of the fatty acids being of the polyunsaturated type, with alpha
      linolenic acid accounting for almost 30% of the total fatty acids. The effect of
      determinant parameters on the performance of the cultures in open tanks was
      evaluated. Operating conditions that allow the maintenance of productive cultures
      were established under semicontinuous regime for 9 months throughout the year.
      Biomass and lutein yields in the open system were not far from those in closed
      tubular photobioreactors, and reached productivity values of 20 g dry biomass,
      containing around 100 mg lutein m(-2) day(-1) in summer. The outdoor culture of
      Muriellopsis sp. in open ponds thus represents a real alternative to established
      systems for the production of lutein.

PMID- 17033776
TI  - [Rational minimally invasive treatment of pAOD: when should a conservative
      approach, PTA, or stent be chosen?].
AB  - In order to obtain optimal results and satisfied patients, rational therapy of
      pAOD should strictly follow national and international society guidelines. In
      particular cases an individual therapeutic concept seems justified beyond these
      guidelines. Based on clinical data and driven by costs, aortic and iliac lesions
      may be treated by PTA or selective stent placement with equal results; however,
      long-term data justify also primary, direct stenting. For treatment of
      infrainguinal and popliteal stenotic lesions primary stenting should be
      restricted to PTA failure (dissection, recoil, occlusion); except for treatment
      of extended lesions, primary stenting compared to PTA alone seems beneficial in
      terms of midterm patency. Endovascular procedures below the knee and at the toe
      should be limited to existing limb-threatening ischemia in order to save the
      extremity; whether PTA or stenting is advantageous has not yet determined.

PMID- 17033777
TI  - Solid-state NMR characterization of the putative membrane anchor of TWD1 from
      Arabidopsis thaliana.
AB  - Structure and membrane interaction of a 31 amino acid residue fragment of the
      membrane bound FKBP-like protein twisted dwarf 1 (TWD1) from Arabidopsis thaliana
      was investigated by solid-state NMR spectroscopy. The studied peptide TWD1(335
      365) contained the putative membrane anchor of the protein (residues 339-357)
      that was previously predicted by sequence hydrophobicity analysis. The TWD1
      peptide was synthesized by standard solid phase peptide synthesis and contained
      three uniformly (13)C- and (15)N-labelled residues (Phe 340, Val 350, Ala 364).
      The peptide was incorporated into either multilamellar vesicles or oriented
      planar membranes composed of an equimolar ternary phospholipid mixture (POPC,
      POPE, POPG), where the POPC was sn-1 chain-deuterated. (31)P NMR spectra of the
      membrane in the absence and in the presence of the peptide showed axially
      symmetric powder patterns indicative of a lamellar bilayer phase. Further, the
      addition of peptide caused a decrease in the lipid hydrocarbon chain order as
      indicated by reduced quadrupolar splittings in the (2)H NMR spectra of the POPC
      in the membrane. The conformation of TWD1(335-365) was investigated by (13)C
      cross-polarization magic-angle spinning NMR spectroscopy. At a temperature of -30
      degrees C all peptide signals were resolved and could be fully assigned in two
      dimensional proton-driven (13)C spin diffusion and (13)C single quantum/double
      quantum correlation experiments. The isotropic chemical shift values for Phe 340
      and Val 350 exhibited the signature of a regular alpha-helix. Chemical shifts
      typical for a random coil conformation were observed for Ala 364 located close to
      the C-terminus of the peptide. Static (15)N NMR spectra of TWD1(335-365) in
      mechanically aligned lipid bilayers demonstrated that the helical segment of
      TWD1(335-365) adopts an orientation perpendicular to the membrane normal. At 30
      degrees C, the peptide undergoes intermediate time scale motions.

PMID- 17033779
TI  - [New study results in cardiology].

PMID- 17033778
TI  - Spectrally resolved time-correlated single photon counting: a novel approach for
      characterization of endogenous fluorescence in isolated cardiac myocytes.
AB  - A new setup for time-resolved fluorescence micro-spectroscopy of cells, based on
      multi-dimensional time-correlated single photon counting, was designed and
      tested. Here we demonstrate that the spectrometer allows fast and reproducible
      measurements of endogenous flavin fluorescence measured directly in living
      cardiac cells after excitation with visible picosecond laser diodes. Two
      complementary approaches for the analysis of spectrally- and time-resolved
      autofluorescence data are presented, comprising the fluorescence decay fitting by
      exponential series and the time-resolved emission spectroscopy analysis. In
      isolated cardiac myocytes, we observed three distinct lifetime pools with
      characteristic lifetime values spanning from picosecond to nanosecond range and
      the time-dependent red shift of the autofluorescence emission spectra. We
      compared obtained results to in vitro recordings of free flavin adenine
      dinucleotide (FAD) and FAD in lipoamide dehydrogenase (LipDH). The developed
      setup combines the strength of both spectral and fluorescence lifetime analysis
      and provides a solid base for the study of complex systems with intrinsic
      fluorescence, such as identification of the individual flavinoprotein components
      in living cardiac cells. This approach therefore constitutes an important
      instrumental advancement towards redox fluorimetry of living cardiomyocytes, with
      the perspective of its applications in the investigation of oxidative metabolic
      state under pathophysiological conditions, such as ischemia and/or metabolic
      disorders.

PMID- 17033780
TI  - [Hypercalcemia in dialysis-dependent renal insufficiency].

PMID- 17033781
TI  - [Treatment of pituitary gland hyperfunction: from acromegaly to prolactinoma].
AB  - Evidence based drug therapy is currently available for the treatment of
      prolactinomas and growth hormone secreting adenomas (acromegaly). Dopamine
      agonists such as bromocriptine, quinagolide or cabergoline represent the standard
      therapy for the treatment of micro- and macro-prolaktinomas. In pregnancy, more
      differentiated, individual and patient-adapted therapeutic procedures have to be
      considered. Transsphenoidal adenomectomy is the treatment of choice for patients
      suffering from acromegaly. If biochemical cure (defined by normalized IGF-1 serum
      levels or by a GH nadir <1 microg/l during a 3-h oral glucose tolerance test)
      cannot be achieved, somatostatin analogues such as octreotide and lanreotide are
      effective. In some cases, dopamine agonists can be added. In therapy-resistant
      cases, growth hormone receptor antagonists can be used.

PMID- 17033782
TI  - [Water and electrolyte disturbances in critical care].
AB  - Management of critically ill patients regularly involves the treatment of water
      and electrolyte disturbances. Moreover, critical care itself may contribute to
      volume overload and electrolyte abnormalities. Initial therapy should be followed
      by consequent diagnostic evaluation. The shift of volume and potassium in severe
      pancreatitis, for example, may lead to a life-threatening situation. In brain
      dead patients, successful organ donation is facilitated by careful maintenance of
      water and electrolyte homeostasis.

PMID- 17033783
TI  - Monte Carlo simulation of intercalated carbon nanotubes.
AB  - Monte Carlo simulations of the single- and double-walled carbon nanotubes (CNT)
      intercalated with different metals have been carried out. The interrelation
      between the length of a CNT, the number and type of metal atoms has also been
      established. This research is aimed at studying intercalated systems based on
      CNTs and d-metals such as Fe and Co. Factors influencing the stability of these
      composites have been determined theoretically by the Monte Carlo method with the
      Tersoff potential. The modeling of CNTs intercalated with metals by the Monte
      Carlo method has proved that there is a correlation between the length of a CNT
      and the number of endo-atoms of specific type. Thus, in the case of a metallic
      CNT (9,0) with length 17 bands (3.60 nm), in contrast to Co atoms, Fe atoms are
      extruded out of the CNT if the number of atoms in the CNT is not less than eight.
      Thus, this paper shows that a CNT of a certain size can be intercalated with no
      more than eight Fe atoms. The systems investigated are stabilized by coordination
      of 3d-atoms close to the CNT wall with a radius-vector of (0.18-0.20) nm. Another
      characteristic feature is that, within the temperature range of (400-700) K,
      small systems exhibit ground-state stabilization which is not characteristic of
      the higher ones. The behavior of Fe and Co endo-atoms between the walls of a
      double-walled carbon nanotube (DW CNT) is explained by a dominating van der Waals
      interaction between the Co atoms themselves, which is not true for the Fe atoms.

PMID- 17033784
TI  - Precursor-directed biosynthesis of 6-deoxyerythronolide B analogues is improved
      by removal of the initial catalytic sites of the polyketide synthase.
AB  - Precursor-directed biosynthesis has been shown to be a powerful tool for the
      production of polyketide analogues that would be difficult or cost prohibitive to
      produce from medicinal chemistry efforts alone. It has been most extensively
      demonstrated using a KS1 null mutation (KS1(0)) to block the first round of
      condensation in the biosynthesis of the erythromycin polyketide synthase (DEBS)
      for the production of analogues of its aglycone, 6-deoxyerythronolide B (6-dEB).
      Here we show that removing the DEBS loading domain and first module (mod1Delta),
      rather than using the KS1(0) system, can lead to an increase in the utilization
      of some chemical precursors and production of 6-dEB analogues (R-6dEB) in both
      Streptomyces coelicolor and Saccharopolyspora erythraea. While the difference in
      utilization of the precursor was diketide specific, in strains fed (2R*, 3S*)-5
      fluoro-3-hydroxy-2-methylpentanoate N-propionylcysteamine thioester, twofold
      increases in both utilization of the diketide and 15-fluoro-6dEB (15F-6dEB)
      production were observed in S. coelicolor, and S. erythraea exhibited a tenfold
      increase in production of 15-fluoro-erythromycin when utilizing the mod1Delta
      rather than the KS1(0) system.

PMID- 17033785
TI  - A comparative linkage map of oilseed rape and its use for QTL analysis of seed
      oil and erucic acid content.
AB  - We have developed a new DH mapping population for oilseed rape, named TNDH, using
      genetically and phenotypically diverse parental lines. We used the population in
      the construction of a high stringency genetic linkage map, consisting of 277
      loci, for use in quantitative genetic analysis. A proportion of the markers had
      been used previously in the construction of linkage maps for Brassica species,
      thus permitting the alignment of maps. The map includes 68 newly developed
      Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of
      A. thaliana. The use of these markers permits the alignment of our linkage map
      with the A. thaliana genome sequence. An additional 74 loci (31 newly developed
      STS markers and 43 loci defined by SSR and RFLP markers that had previously been
      used in published linkage maps) were added to the map. These markers increased
      the resolution of alignment of the newly constructed linkage map with existing
      Brassica linkage maps and the A. thaliana genome sequence. We conducted field
      trials with the TNDH population at two sites, and over 2 years, and identified
      reproducible QTL for seed oil content and erucic acid content. The results
      provide new insights into the genetic control of seed oil and erucic acid content
      in oilseed rape, and demonstrate the utility of the linkage map and population.

PMID- 17033786
TI  - Diversity arrays technology (DArT) for high-throughput profiling of the hexaploid
      wheat genome.
AB  - Despite a substantial investment in the development of panels of single
      nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR)
      technology with a limited multiplexing capability remains a standard, even for
      applications requiring whole-genome information. Diversity arrays technology
      (DArT) types hundreds to thousands of genomic loci in parallel, as previously
      demonstrated in a number diploid plant species. Here we show that DArT performs
      similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.).
      The methodology previously used to generate DArT fingerprints of barley also
      generated a large number of high-quality markers in wheat (99.8% allele-calling
      concordance and approximately 95% call rate). The genetic relationships among
      bread wheat cultivars revealed by DArT coincided with knowledge generated with
      other methods, and even closely related cultivars could be distinguished. To
      verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook x
      Halberd doubled haploid lines for which a framework (FW) map comprising a total
      of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified
      fragment length polymorphism (AFLP) markers was available. We added an equal
      number of DArT markers to this data set and also incorporated 71 sequence tagged
      microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores,
      call rates and the degree of genome coverage indicated that the quality and
      information content of the DArT data set was comparable to that of the combined
      SSR/RFLP/AFLP data set of the FW map.

PMID- 17033787
TI  - [Hyperplastic scars and keloids: part II: Surgical and non-surgical treatment
      modalities].
AB  - Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and
      keloid formation, causing functional and cosmetic deformities, discomfort,
      psychological stress, and patient dissatisfaction. Scar management, both surgical
      and non-surgical, continue to be important issues for the facial plastic surgeon.
      Many techniques for the management of hypertrophic scars and keloids have been
      proven through extensive use, but few are supported by prospective studies with
      adequate control groups. Several new therapies showed good results in small-scale
      trials, but these have not been repeated in larger trials with long-term follow
      up. This article presents an overview of the available therapies and provides
      recommendations for the treatment of abnormal scarring. The recommendations focus
      on the management of hypertrophic scars and keloids. Strategies for the
      management of keloids and hypertrophic scars are of continuing interest and
      studies are necessary to understand the basic mechanisms causing aberrant wound
      healing. In addition, an overview of new developments in molecular wound
      management and gene therapy, as they relate to facial plastic surgery, is
      provided.

PMID- 17033788
TI  - Mycoplasma hominis osteitis in an immunocompetent man.
AB  - Mycoplasma hominis has been associated with pelvic inflammatory illness,
      postpartum and neonatal infections and respiratory tract diseases. It is rarely
      isolated from patients with other infections. Reported here is a case of tibial
      osteitis that occurred in a 16-year-old immunocompetent man. Clinical and
      laboratory findings improved under treatment with clindamycin and
      fluoroquinolones.

PMID- 17033789
TI  - Prevalence of Borrelia burgdorferi s.l. and Anaplasma phagocytophilum in the wood
      tick Ixodes ricinus in the Province of Trento, Italy.

PMID- 17033790
TI  - Catheter-associated fungemia due to Exophiala oligosperma in a leukemic child and
      review of fungemia cases caused by Exophiala species.
AB  - A case of catheter-associated fungemia due to Exophiala oligosperma in a 3-year
      old leukemic child is presented. The etiologic agent was isolated from blood
      specimens and the catheter tip. The isolate was identified by its morphological
      characteristics and DNA sequencing of the internal transcribed spacer region of
      rDNA. Despite initial amphotericin B and itraconazole therapy, the child's fever
      subsided only after removal of the catheter. A review of the medical literature
      revealed 29 cases of infection due to Exophiala species. Twenty-three of these 29
      patients had a CVC in place when they developed fever or other manifestations of
      fungemia. Withdrawal of the CVC together with amphotericin B and/or itraconazole
      therapy generally resulted in a good prognosis.

PMID- 17033792
TI  - Metabolic response during intermittent graded sprint running in moderate
      hypobaric hypoxia in competitive middle-distance runners.
AB  - The purpose of this study was to determine whether the metabolic response and
      running performance during intermittent graded sprint running were affected by
      moderate hypobaric hypoxia (H; 2,500 m above sea level) in competitive middle
      distance runners. Nine male runners performed intermittent graded sprint running
      until exhaustion, to evaluate the metabolic response and running performance in H
      and normobaric normoxia (N). The test constructed of incremental (25 m min(-1))
      20 s running bouts (4 degrees inclination) interspaced with 100 s recovery
      periods. Maximal running speed was not different between conditions [453 (7) m
      min(-1) vs. 458 (4) m min(-1) in N vs. H]. V(O2) at each speed was lower in H
      than N (ANOVA; P < 0.05). Although, oxygen deficit (D(O2)) at each speed was not
      different between N and H (ANOVA; P = 0.1), total accumulated D(O2) in all bouts
      was significantly higher in H than N [165 (10) ml kg(-1) in N and 173 (10) ml kg(
      1) in H]. The ratio of D(O2).V(O2)(-1) was similar in all bouts, but higher in H
      than N. These results suggest that intermittent graded sprint running performance
      is not affected by moderate hypobaria despite a reduction in the energy supplied
      by aerobic metabolism due to a compensatory increase in the energy supplied by
      the anaerobic metabolism in competitive middle-distance runners.

PMID- 17033791
TI  - Effect of gravity in long-term vitreous tamponade: in vivo investigation using
      perfluorocarbon liquids and semi-fluorinated alkanes.
AB  - PURPOSE: In order to investigate whether gravity is the reason for retinal
      degeneration in long-term vitreous tamponade, perfluorohexyloctane (F6H8),
      perfluorodecalin (PFD), and a mixture of F6H8/PFD were compared. MATERIALS AND
      METHODS: Each group of 5 rabbits received a 3-month tamponade with either PFD
      (pure) (1.93 g/cm(3)), F6H8 (pure) (1.33 g/cm(3)), or a 1:1 mixture of F6H8/PFD
      (1.62 g/cm(3)). Electroretinograms (ERG) were performed pre- and postoperatively.
      Lower and upper retinal areas were compared using immunohistochemical methods.
      Transmission electron microscopy was performed to investigate alterations in the
      photoreceptors. RESULTS: All three substances were tolerated well in rabbit eyes
      for up to 3 months. Dispersion was seen earliest with PFD and latest with pure
      F6H8. None of the substances demonstrated inflammatory reactions or vascular
      alterations. ERGs were not considerably altered with any of the substances.
      Histology of the retina showed alterations in the cell counts within the inner
      and outer nuclear layer that were not attributable to the gravity of the
      tamponading agent. CONCLUSION: In contrast to previously published work, this
      study did not detect any tamponade-related structural damage of the retina after
      a 3-months tamponade in the rabbit model. Based upon this study, we conclude that
      gravity might not be causally linked to retinal damage.

PMID- 17033794
TI  - [Left hemifacial flushing and sweating].

PMID- 17033793
TI  - Effects of two types of inactivity on the number of white blood cells in rats.
AB  - Prolonged inactivity is known to induce changes in responses of many
      physiological defense systems such as the hypothalamo-hypophyseal-adrenocortical
      axis, the sympathetic nervous system, and immuno-responsive systems. However,
      effects of various types of inactivity on immuno-responsive systems are still
      unknown. Therefore, the effects of two types of inactivity (immobilization: IMM
      and whole body suspension: WBS) on the number of white blood cells were studied
      in rats. Rats were divided into the control group and each inactivity group to
      compare the number of total white blood cells, lymphocytes, monocyte, neutrophil,
      eosinophil, and basophil during the experimental periods. Both IMM and WBS were
      maintained for 11 days. IMM markedly increased the number of total white blood
      cells, monocyte, neutrophil, and eosinophil in the 1st to 10th day. However, the
      number of total white blood cells, monocyte, neutrophil, and eosinophil during
      the experiment of WBS were characterized by the presence of a lag phase followed
      by the significant increased actions. IMM did not change the number of basophil
      during the experimental period. However, WBS increased the number of basophil in
      the 1st to 8th day to 2.8-4.8 times, compared with the values of the control.
      Both IMM and WBS did not change the number of lymphocytes. From these results,
      WBS increases the number of natural immunity cells without changing acquired
      immunity cells, and there are different responses in the number of total white
      blood cells, monocyte, neutrophil, eosinophil, and basophil between IMM and WBS.

PMID- 17033795
TI  - The radiologist assistant: the solution to radiology workforce needs.
AB  - Since 2003 the radiologist assistant (RA) was introduced in response to the
      severe shortage of radiologists and the increased demand for medical imaging
      services. Other non-physician clinicians, such as PAs, currently play an
      important role in the medical imaging environment. The article discusses the
      reasons physician assistants have found favor with interventional radiologists,
      and advocates an increased role for physician extenders in Radiology. It refutes
      the skeptics who question whether the new profession will alleviate the manpower
      crisis in Radiology. The authors suggest that RAs are the ideal complement to
      radiologists; and based on their radiologic technology background, have a vested
      interest in the field.

PMID- 17033797
TI  - The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumours: a
      comment on concepts and classification of mixed exocrine-endocrine neoplasms.
AB  - Terms such as "mixed endocrine-exocrine carcinoma" (MEEC) and "adenocarcinoma
      with neuroendocrine (NE) differentiation" (ADC-NE) identify tumours belonging to
      the spectrum of neoplasms with divergent exocrine and (neuro)endocrine
      differentiation. These tumours display variable quantitative extent of the two
      components, potentially ranging from 1 to 99%, and variable structural patterns,
      ranging from single scattered NE cells to a well-defined NE tumour cell
      population organized in organoid, trabecular or solid growth patterns. In the
      present report, the grey zone of tumours/carcinomas with mixed NE and non-NE
      features is explored for various organs. From a practical point of view, MEECs
      differ from carcinomas with focal NE differentiation by (1) the extension of each
      component (more than 30%) and (2) the structural pattern of the NE component,
      either organoid for well-differentiated or solid/diffuse for poorly
      differentiated cases. In MEECs, the most aggressive cell population drives the
      clinical behaviour. Conversely, ADC-NE generally do not show a different clinical
      outcome, compared to the corresponding conventional forms, except for prostatic
      adenocarcinoma, in which NE cells are a negative prognostic factor. The
      recognition of MEECs may be of relevance for a targeted therapeutic strategy,
      foreseeing the use of biotherapies similar to those proposed for pure NE tumours.

PMID- 17033796
TI  - Disease modifying genes in cystic fibrosis: therapeutic option or one-way road?
AB  - Cystic fibrosis (CF) is the most common genetic disease among Caucasians and is
      caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF
      affects multiple organs but lung disease is the major determinant for morbidity
      and mortality. Many studies have focussed on the correlation between CFTR
      genotype and severity of disease. Since patients with identical CFTR mutations
      often show considerable variability in disease progression, genes other than CFTR
      are thought to have the potential to modify the course of lung disease in CF
      patients. Therefore, identification of CF-modifying genes has become the goal of
      several studies over the last 15 years. Pharmaceutical approaches for CF lung
      disease have been developed regardless of the underlying genetic defect and in
      general target symptoms such as airway obstruction and treatment of bacterial
      infection. Analysing the pathophysiological processes of modifiers may lead to
      the discovery of pathways involved in CF pathophysiology and possibly to the
      design of new therapeutics. The purpose of this review is not only to list
      potential CFTR modifier genes, but also to discuss new therapeutic strategies
      that could be derived from knowledge of these CF modifiers.

PMID- 17033798
TI  - Expression of Epstein-Barr virus (EBV)-encoded latent membrane proteins and STAT3
      activation in nasopharyngeal carcinoma.
AB  - The Epstein-Barr virus (EBV) is associated with virtually all cases of
      undifferentiated nasopharyngeal carcinoma (NPC), and it was proposed that the EBV
      encoded transforming protein, latent membrane protein (LMP) 1, may play a role in
      the neoplastic process. It was proposed recently that LMP1 expression in
      epithelial cells may be regulated through a loop involving activated signal
      transducer and activator of transcription 3 (STAT3), LMP1, LMP1-mediated
      induction of interleukin (IL)-6 expression and STAT3 activation through the IL-6
      receptor. This autoregulatory loop may be suppressed by another viral protein,
      LMP2A, an effect which in turn can be overcome by exogenous IL-6. Here we show
      that, as expected, expression of LMP1 and LMP2A tend to be exclusive in NPC
      tumours. Rare cases showing a co-expression of both proteins can be explained by
      STAT3 activation via the receptors for IL-6 or epidermal growth factor. STAT3
      activation was a consistent feature of NPC tumour cells. However, in most cases,
      this was not accompanied by detectable expression of LMP1, suggesting either that
      LMP2A expression may suffice to suppress LMP1 expression or that additional
      factors may be operational. This study emphasises the need to correlate in vitro
      results with observational studies of ex vivo tumour tissues.

PMID- 17033799
TI  - Intrahepatic sarcomatoid cholangiocarcinoma of round cell variant: a case report
      and immunohistochemical studies.
AB  - Sarcomatoid transformation was observed in 4.5% of autopsied cases of
      intrahepatic cholangiocarcinoma. Here, we report a case of intrahepatic
      sarcomatoid cholangiocarcinoma with round cell feature, extremely rare variant.
      An 87-year-old man was incidentally found to have a tumor in the left lobe of the
      liver by abdominal computed tomography scans. The patient was clinically
      diagnosed to have intrahepatic cholangiocarcinoma and received palliative care
      without specific treatment. He died of hepatic insufficiency 3 months after the
      diagnosis. The autopsied liver specimens showed a reddish gray tumor of 4.0x2.8
      cm in size. Histologically, the tumor was centrally hemorrhagic and necrotic and
      was composed of tubular adenocarcinoma and a round cell component, which has an
      eccentrically located nucleus and eosinophilic cytoplasm without mucin
      production. Immunohistochemically, the adenocarcinoma cells expressed cytokeratin
      19 and beta-catenin in their cytoplasm, with E-cadherin and CD44s at the plasma
      membrane. In the round cells, cytokeratin 19 and vimentin was detected in their
      cytoplasm and CD44s at the plasma membrane. E-cadherin immunoreactivity was
      weakly present in their cytoplasm and beta-catenin was negative. Loss or
      reduction of the E-cadherin and beta-catenin expressions and overexpression of
      CD44s in the round cells are suggested to be contributed to the high propensity
      for lymphatic permeation and poor prognosis.

PMID- 17033800
TI  - Utilization of low-dose multidetector CT and virtual bronchoscopy in children
      with suspected foreign body aspiration.
AB  - BACKGROUND: Foreign body aspiration is common in children, especially those under
      3 years of age. Chest radiography and CT are the main imaging modalities for the
      evaluation of these children. Management of children with suspected foreign body
      aspiration (SFBA) mainly depends on radiological findings. OBJECTIVE: To
      investigate the potential use of low-dose multidetector CT (MDCT) and virtual
      bronchoscopy (VB) in the evaluation and management of SFBA in children. MATERIALS
      AND METHODS: Included in the study were 37 children (17 girls, 20 boys; age 4
      months to 10 years, mean 32 months) with SFBA. Chest radiographs were obtained
      prior to MDCT in all patients. MDCT was performed using a low-dose technique. VB
      images were obtained in the same session. Conventional bronchoscopy (CB) was
      performed within 24 h on patients in whom an obstructive abnormality had been
      found by MDCT and VB. RESULTS: Obstructive pathology was found in 16 (43.25%) of
      the 37 patients using MDCT and VB. In 13 of these patients, foreign bodies were
      detected and removed via CB. The foreign bodies were located in the right main
      bronchus (n = 5), in the bronchus intermedius (n = 6), in the medial segment of
      the middle lobe bronchus (n = 1), and in the left main bronchus (n = 1). In the
      remaining three patients, the diagnosis was false-positive for an obstructive
      pathology by MDCT and VB; the final diagnoses were secretions (n = 2) and
      schwannoma (n = 1), as demonstrated by CB. In 21 patients in whom no obstructive
      pathology was detected by MDCT and VB, CB was not performed. These patients were
      followed for 5-20 months without any recurrent obstructive symptomatology.
      CONCLUSIONS: Low-dose MDCT and VB are non-invasive radiological modalities that
      can be used easily in the investigation of SFBA in children. MDCT and VB provide
      the exact location of the obstructive pathology prior to CB. If obstructive
      pathology is depicted with MDCT and VB, CB should be performed either for
      confirmation of the diagnosis or for the diagnosis of an alternative cause for
      the obstruction. In cases where no obstructive pathology is detected by MDCT and
      VB, CB may not be clinically useful.

PMID- 17033801
TI  - Savanna fires increase rates and distances of seed dispersal by ants.
AB  - Myrmecochory (seed dispersal by ants) is a prominent dispersal mechanism in many
      environments, and can play a key role in local vegetation dynamics. Here we
      investigate its interaction with another key process in vegetation dynamics-fire.
      We examine ant dispersal of seeds immediately before and after experimental
      burning in an Australian tropical savanna, one of the world's most fire-prone
      ecosystems. Specifically, our study addressed the effects of burning on: (1) the
      composition of ants removing seeds, (2) number of seed removals, and (3) distance
      of seed dispersal. Fire led to higher rates of seed removal post-fire when
      compared with unburnt habitat, and markedly altered dispersal distance, with mean
      dispersal distance increasing more than twofold (from 1.6 to 3.8 m), and many
      distance dispersal events greater than the pre-fire maximum (7.55 m) being
      recorded. These changes were due primarily to longer foraging ranges of species
      of Iridomyrmex, most likely in response to the simplification of their foraging
      landscape. The significance of enhanced seed-removal rates and distance dispersal
      for seedling establishment is unclear because the benefits to plants in having
      their seeds dispersed by ants in northern Australia are poorly known. However, an
      enhanced removal rate would enhance any benefit of reduced predation by rodents.
      Similarly, the broader range of dispersal distances would appear to benefit
      plants in terms of reduced parent-offspring conflict and sibling competition, and
      the location of favourable seedling microsites. Given the high frequency of fire
      in Australian tropical savannas, enhanced benefits of seed dispersal by ants
      would apply for much of the year.

PMID- 17033802
TI  - Is microbial community composition in boreal forest soils determined by pH, C-to
      N ratio, the trees, or all three?
AB  - In Fennoscandian boreal forests, soil pH and N supply generally increase downhill
      as a result of water transport of base cations and N, respectively.
      Simultaneously, forest productivity increases, the understory changes from
      ericaceous dwarf shrubs to tall herbs; in the soil, fungi decrease whereas
      bacteria increase. The composition of the soil microbial community is mainly
      thought to be controlled by the pH and C-to-N ratio of the substrate. However,
      the latter also determines the N supply to plants, the plant community
      composition, and should also affect plant allocation of C below ground to roots
      and a major functional group of microbes, mycorrhizal fungi. We used phospholipid
      fatty acids (PLFAs) to analyze the potential importance of mycorrhizal fungi by
      comparing the microbial community composition in a tree-girdling experiment,
      where tree belowground C allocation was terminated, and in a long-term (34 years)
      N loading experiment, with the shifts across a natural pH and N supply gradient.
      Both tree girdling and N loading caused a decline of ca. 45% of the fungal
      biomarker PLFA 18:2omega6,9, suggesting a common mechanism, i.e., that N loading
      caused a decrease in the C supply to ectomycorrhizal fungi just as tree girdling
      did. The total abundance of bacterial PLFAs did not respond to tree girdling or
      to N loading, in which cases the pH (of the mor layer) did not change
      appreciably, but bacterial PLFAs increased considerably when pH increased across
      the natural gradient. Fungal biomass was high only in acid soil (pH < 4.1) with a
      high C-to-N ratio (>38). According to a principal component analysis, the soil C
      to-N ratio was as good as predictor of microbial community structure as pH. Our
      study thus indicated the soil C-to-N ratio, and the response of trees to this
      ratio, as important factors that together with soil pH influence soil microbial
      community composition.

PMID- 17033804
TI  - Successful treatment of Wolman disease by unrelated umbilical cord blood
      transplantation.
AB  - Wolman disease is a rapidly fatal lysosomal storage disease caused by the
      complete absence of lysosomal acid lipase activity. We report the cure of an
      infant with Wolman disease following transplantation of unrelated HLA-mismatched
      umbilical cord blood-derived stem cells. Umbilical cord blood was chosen as the
      stem-cell source because of its immediate availability and reduced tendency to
      cause graft-versus-host disease. The transplantation resulted in restoration of
      normal acid lipase levels before the onset of permanent end-organ damage. Four
      years after transplantation, the patient is thriving and has normal levels of
      acid lipase in peripheral blood cells. To our knowledge, this is the first report
      of a successful unrelated cord blood transplant in a patient with Wolman disease.
      Umbilical cord stem cells transplantation can restore acid lipase levels in
      Wolman disease, and if performed early, can cure the disease.

PMID- 17033803
TI  - Variations in prevalence of attention deficit hyperactivity disorder worldwide.
AB  - Attention deficit hyperactivity disorder (ADHD) is among the most common,
      intensely investigated, and yet diagnostically controversial neurobehavioral
      conditions of childhood. The prevalence of ADHD has been reported with great
      variations among different studies, ranging from 2.2% to 17.8%. The aim of this
      review was to investigate the variables that influence the prevalence of ADHD and
      to derive a best estimate for the prevalence of the disorder. We reviewed all the
      39 studies on ADHD prevalence appearing in the Pubmed and published since 1992.
      These studies indicate that ADHD is more common in boys than girls, in younger
      than older children and adolescents, in one-setting rather than two-setting
      screening studies, in studies based on DSM-IV rather than DSM-III-R criteria.
      Additional factors that may well influence prevalence rates include source of
      information and assessment of clinical impairment. In conclusion, our findings
      suggest that population characteristics, methodology features, ethnic and
      cultural differences and diagnostic criteria involved in studies affect the
      prevalence of ADHD. Standardized designs may lead to firm conclusions on the true
      prevalence of ADHD, the estimation of which seems impossible to be achieved by
      reviewing the already existing literature.

PMID- 17033805
TI  - Slow-growing lambdoid melanotic neuroectodermal tumor of infancy.
AB  - Melanotic neuroectodermal tumors of infancy are rare neoplasms that occasionally
      may involve the skull. Usually such lesions present as an anterior fontanelle
      mass that grows rapidly. Very rarely, skull lesions are located at different
      sites and have an indolent course, thus making the diagnosis more difficult. To
      illustrate this latter presentation, we present a case of a slowly growing
      melanotic neuroectodermal tumor of infancy located on the right lambdoid suture.

PMID- 17033806
TI  - Impact of amoxicillin, associated or not with clavulanic acid, on pharyngeal
      colonization and selection of Streptococcus pneumoniae resistance in children
      under 5 years of age.
AB  - Among young children, pneumococcal nasopharyngeal colonization (NPC) rates of
      >90% have been described. The aim of our study was to assess the effect of
      amoxicillin exposure on the NPC. From Dec 2001 to Feb 2004, less than 5 years old
      children with respiratory symptoms and fever who were prescribed amoxicillin were
      eligible. Three nasopharyngeal swabs were taken: at the time of the initial visit
      (IV), 60 hours after amoxicillin discontinuation (end of treatment visit, ETV),
      and 4 weeks later (follow-up visit, FUV). One hundred and thirty four children
      were included. NPC was detected in 58.5%, 42.9% and 51% of <1, 1-2 and >2 years
      old children respectively (NS). Vaccine serotypes (VS) or vaccine-related
      serotypes (VRS) were identified in 80%, 40% and 55% of <1-year-old, 1-2 year-old
      and >2-year-old children respectively (NS). The proportion of PNSSP was 60% in <1
      year-old children, 43% in 1-2 year-old children and 40% in >2-year-old children
      (NS). 49 out of 134 (36.5%) children completed the three study visits. 51%, 22.4%
      and 46.9% of those were colonized at IV, ETV and FUV, respectively (p=0.007). The
      percentage of resistant SP was 28%, 45.5% and 8.7% (p=0.05) for penicillin. In
      children <1 year of age, a higher proportion of SP colonization, presence of VS
      and PNSSP was found. A downfall of NPC at the end of therapy was observed. NPC
      returned to baseline levels thanks to "de novo" colonization in half of the
      cases, a few weeks after.

PMID- 17033807
TI  - Predictive risk factors for coronary artery abnormalities in Kawasaki disease.
AB  - Clinical characteristics to predict the development of coronary artery
      abnormalities (CAA) in Kawasaki disease (KD) were assessed by reviewing medical
      records of patients diagnosed with KD at Korea University Medical Center from
      March 2001 to February 2005. Of the 285 patients diagnosed with KD, 19 developed
      CAA (6.7%). Compared with the CAA(-) group, the CAA(+) group had a longer
      duration of fever after intravenous gamma-globulin (IVGG) injection (2.4+/-2.9
      vs. 1.5+/-1.2 days, p=0.008) and higher C-reactive protein (CRP)(12.3+/-7.8 vs.
      8.7+/-7.1 mg/dL, p=0.038). In particular, the CAA(+) group tended to have more
      than 7 days of fever before IVGG and more than 3 days of fever after IVGG (26.3
      vs. 5.3%, p<0.001; 26.3 vs. 6.4%, p=0.002). When the IVGG responsiveness was
      defined by the presence of defervescence within 3 days after IVGG, IVGG-non
      responders showed a higher incidence of CAA (22.7 vs. 5.3%, p=0.002). Non
      responders had a longer duration of fever after IVGG (5.5+/-1.9 vs. 1.2+/-0.6
      days, p<0.001) and a significantly increased CRP, AST, ALT and total bilirubin.
      Multivariate regression analysis for CAA showed that the only factor
      significantly associated with the development of CAA was total fever that lasted
      for longer than 8 days (OR=4.052, 95% CI=1.151-14.263, p=0.0293). Conclusively,
      the most important predictor of CAA in KD is total duration of fever longer than
      8 days. Early identification of IVGG non-responders and active therapeutic
      intervention for fever in KD cases might decrease the incidence of CAA.

PMID- 17033808
TI  - Ecotype-specific and chromosome-specific expansion of variant centromeric
      satellites in Arabidopsis thaliana.
AB  - Despite the conserved roles and conserved protein machineries of centromeres,
      their nucleotide sequences can be highly diverse even among related species. The
      diversity reflects rapid evolution, but the underlying mechanism is largely
      unknown. One approach to monitor rapid evolution is examination of intra-specific
      variation. Here we report variant centromeric satellites of Arabidopsis thaliana
      found through survey of 103 natural accessions (ecotypes). Among them, a cluster
      of variant centromeric satellites was detected in one ecotype, Cape Verde Islands
      (Cvi). Recombinant inbred mapping revealed that the variant satellites are
      distributed in centromeric region of the chromosome 5 (CEN5) of this ecotype.
      This apparently recent variant accumulation is associated with large deletion of
      a pericentromeric region and the expansion of satellite region. The variant
      satellite was bound to HTR12 (centromeric variant histone H3), although expansion
      of the satellite was not associated with comparable increase in the HTR12
      binding. The results suggest that variant satellites with centromere function can
      rapidly accumulate in one centromere, supporting the model that the satellite
      repeats in the array are homogenized by occasional unequal crossing-over, which
      has a potential to generate an expansion of local sequence variants within a
      centromere cluster.

PMID- 17033809
TI  - Structure and transcriptional impact of divergent repetitive elements inserted
      within Phanerochaete chrysosporium strain RP-78 genes.
AB  - We describe the structure, organization, and transcriptional impact of repetitive
      elements within the lignin-degrading basidiomycete, Phanerochaete chrysosporium.
      Searches of the P. chrysosporium genome revealed five copies of pce1, a ~1,750-nt
      non-autonomous, class II element. Alleles encoding a putative glucosyltransferase
      and a cytochrome P450 harbor pce insertions and produce incomplete transcripts.
      Class I elements included pcret1, an intact 8.14-kb gypsy-like retrotransposon
      inserted within a member of the multicopper oxidase gene family. Additionally, we
      describe a complex insertion of nested transposons within another putative
      cytochrome P450 gene. The disrupted allele lies within a cluster of >14 genes,
      all of which encode family 64 cytochrome P450s. Components of the insertion
      include a disjoint copia-like element, pcret3, the pol domain of a second
      retroelement, pcret2, and a duplication of an extended ORF of unknown function.
      As in the case of the pce elements, pcret1 and pcret2/3 insertions are confined
      to single alleles, transcripts of which are truncated. The corresponding wild
      type alleles are apparently unaffected. In aggregate, P. chrysosporium harbors a
      complex array of repetitive elements, at least five of which directly influence
      expression of genes within families of structurally related sequences.

PMID- 17033810
TI  - Molecular genetic analysis of five spike-related traits in wheat using RIL and
      immortalized F2 populations.
AB  - Kernel number per spike is one of the most important yield components of wheat.
      To map QTLs related to kernel number including spike length (SPL), spikelet
      number per spike (SPN), fertile spikelet number (FSPN), sterile spikelet number
      (SSPN) and compactness, and to characterize the inheritance modes of the QTLs and
      two-locus interactions, 136 recombinant inbred lines (RILs) derived from
      'Nanda2419' x 'Wangshuibai' and an immortalized F(2 )population (IF(2)) generated
      by randomly permutated intermating of these RILs were investigated. QTL mapping
      made use of the previously constructed over 3300 cM linkage map of the RIL
      population. Three, five, two, two and six chromosome regions were identified,
      respectively, for their association with SPL, SPN, FSPN, SSPN, and compactness in
      at least two of the three environments examined. All compactness QTLs but one
      shared the respective intervals of QSpn.nau-5A and the SPL QTLs. Xcfd46-Xwmc702
      interval on chromosome 7D was related to all traits but SSPN and had consistently
      the largest effects. The fact that not all the compactness QTL intervals were
      related to both SPL and SPN indicates that compactness is regulated by different
      mechanisms. Interval coincidence between QTLs of SPL and SPN and between QTLs of
      FSPN and SSPN was minimal. For all the traits, favorable alleles exist in both
      parents. Inheritance modes from additiveness to overdominance of the QTLs were
      revealed and two-locus interactions were detected, implying that the traits
      studied are under complex genetic control. The results could contribute to wheat
      yield improvement and better use of Wangshuibai and Nanda2419 the two special
      germplasms in wheat breeding program.

PMID- 17033811
TI  - Genome-wide analysis of the stress associated protein (SAP) gene family
      containing A20/AN1 zinc-finger(s) in rice and their phylogenetic relationship
      with Arabidopsis.
AB  - Proteins with the A20/AN1 zinc-finger domain are present in all eukaryotes and
      are well characterized in animals, but little is known about their function in
      plants. Earlier, we have identified an A20/AN1 zinc-finger containing stress
      associated protein 1 gene (SAP1) in rice and validated its function in abiotic
      stress tolerance. In this study, genome-wide survey of genes encoding proteins
      possessing A20/AN1 zinc-finger, named SAP gene family, has been carried out in
      rice and Arabidopsis. The genomic distribution and gene architecture as well as
      domain structure and phylogenetic relationship of encoded proteins numbering 18
      and 14 in rice and Arabidopsis, respectively, have been studied. Expression
      analysis of the rice SAP family was done to investigate their response under
      abiotic stress conditions. All the genes were inducible by one or the other
      abiotic stresses indicating that the OsSAP gene family is an important component
      of stress response in rice. Manipulation of their expression and identification
      of their superior alleles should help confer stress tolerance in target crops.

PMID- 17033812
TI  - Phosphate starvation responses are mediated by sugar signaling in Arabidopsis.
AB  - Phosphate (Pi) is one of the least available plant nutrients in soils. It is
      associated with dynamic changes in carbon fluxes and several crucial processes
      that regulate plant growth and development. Pi levels regulate the expression of
      large number of genes including those involved in photosynthesis and carbon
      metabolism. Herein we show that sugar is required for Pi starvation responses
      including changes in root architecture and expression of phosphate starvation
      induced (PSI) genes in Arabidopsis. Active photosynthesis or the supplementation
      of sugar in the medium was essential for the expression of PSI genes under Pi
      limiting conditions. Expression of these genes was not only induced by sucrose
      but also detected, albeit at reduced levels, with other metabolizable sugars. Non
      metabolizable sugar analogs did not induce the expression of PSI genes. Although
      sugar input appears to be down-stream of initial Pi sensing, it is absolutely
      required for the completion of the PSI signaling pathway. Altered expression of
      PSI genes in the hexokinase signaling mutant gin2 indicates that hexokinase
      dependent signaling is involved in this process. The study provides evidence for
      requirement of sugars in PSI signaling and evokes a role for hexokinase in some
      components of Pi response mechanism.

PMID- 17033813
TI  - Sustained beneficial effect of intravenous bisphosphonates after their
      discontinuation in children.
AB  - We studied if the beneficial effects of bisphosphonates are maintained after
      their discontinuation, and whether adverse effects may develop. Seventeen
      children in whom I.V. bisphosphonates were discontinued for at least 12 months
      were included. Fracture rate (FR), skeletal pain, bone mineral density of total
      body (TB) and spine L(2-4), skeletal radiographs, bone markers and kidney
      functions were compared between: (a) before treatment, (b) end of treatment, and
      (c) last follow-up. Mean treatment duration was 22+/-2 months (6-43) and follow
      up 26+/-2 months (18-44). FR (mean +/- SD) decreased from 0.74+/-0.21/year before
      treatment to 0.35+/-0.11/year after treatment and 0.20+/-0.09/year at follow-up
      (p<0.05). Three children had bone pain before treatment, six during treatment and
      none at end of follow-up (p<0.05). TB Z-score increased from -1.24+/-0.50 at
      baseline to -0.37+/-0.44 at end of treatment and -0.39+/-0.37 at follow-up
      (p<0.05). Spinal Z-score increased from -1.65+/-0.57 to -0.34+/-0.56 and 0.19+/
      0.49, respectively (p<0.05). Bone turnover markers showed sustained effect of
      bisphosphonates. No adverse effects on kidney functions or skeletal radiographs
      were noted. We conclude that I.V. bisphosphonates continue to exert their
      beneficial effect for a mean of 26+/-2 months after their discontinuation;
      therefore, once therapeutic goals are achieved, the medication can be withheld,
      followed by periodic re-evaluation.

PMID- 17033814
TI  - Optical mapping of V(m) and Ca(i)(2+) in a model of arrhythmias induced by local
      catecholamine application in patterned cell cultures.
AB  - Catecholamines are known to provoke cardiac arrhythmias, but important aspects
      such as localization of the arrhythmia source in multicellular tissue and exact
      ionic mechanisms are not well-known. In this work, a multicellular model of
      arrhythmias caused by local epinephrine application was developed; V (m) and
      Ca(i)(2+) changes at the arrhythmia source were measured using fluorescent dyes
      and high-resolution optical mapping. Cultured strands of neonatal rat myocytes
      (width approximately 0.4 mm) were produced by patterned growth. Epinephrine (1
      micromol/l) was applied over an area of 0.3-0.6 mm via two micropipettes, and
      strands were stimulated by burst pacing. Local epinephrine application caused
      triggered arrhythmias with cycle lengths of 202-379 ms and duration of >10 s in 9
      out of 16 preparations. Optical V(m) mapping demonstrated that in 78% of cases,
      the source of arrhythmia was located at the boundary of the locally perfused
      area. Staining with Ca(i)(2+)-sensitive dye Fluo-4 prevented arrhythmia induction
      in most cases (85%) likely due to Ca(2+) buffering by the dye. Optical Ca(i)(2+)
      mapping revealed non-propagated Ca(i)(2+) oscillations at the boundary of the
      locally perfused area in 45% cases. In conclusion, we developed a new model of
      catecholamine-dependent arrhythmias allowing mapping of V(m) and Ca(i)(2+) at the
      arrhythmia source with microscopic resolution. The arrhythmias typically
      originated from the boundary of the epinephrine-perfused area. The location of
      the arrhythmia source correlated with localized Ca(i)(2+) oscillations suggesting
      that arrhythmias were caused by Ca(i)(2+) overload at these locations.

PMID- 17033815
TI  - Rooting and vitality of poinsettia cuttings was increased by arbuscular
      mycorrhiza in the donor plants.
AB  - In this paper, we provide evidence that the rooting performance of cuttings can
      be improved by the arbuscular mycorrhizal (AM) symbiosis of donor plants.
      Poinsettia stock plants were inoculated with the Glomus intraradices isolate H510
      and grown in three different cultivation systems (two organic and one
      conventional). AM colonization was not related to P availability in the
      substrate. Decay of the excised cuttings in response to unfavorable postharvest
      storage conditions was significantly reduced by AM colonization of the stock
      plants. In most cases, AM significantly promoted the formation of adventitious
      roots in the stored cuttings. The strongest effect of AM was found when donor
      plants were grown in a modified organic substrate; then AM-conditioned cuttings
      showed higher leaf sugar levels and a changed kinetic of carbohydrates during
      storage. Analyses of N, P, and K in cuttings did not indicate a nutritional
      effect. The results support the idea that an altered carbohydrate metabolism and
      plant hormones can contribute to improved rooting performance of cuttings excised
      from mycorrhizal donor plants.

PMID- 17033816
TI  - The ectomycorrhizal fungus Scleroderma bermudense alleviates salt stress in
      seagrape (Coccoloba uvifera L.) seedlings.
AB  - The purpose of this study was to test the capacity of the ectomycorrhizal (ECM)
      fungus, Scleroderma bermudense, to alleviate saline stress in seagrape (Coccoloba
      uvifera L.) seedlings. Plants were grown over a range (0, 200, 350 and 500 mM) of
      NaCl levels for 12 weeks, after 4 weeks of non-saline pre-treatment under
      greenhouse conditions. Growth and mineral nutrition of the seagrape seedlings
      were stimulated by S. bermudense regardless of salt stress. Although ECM
      colonization was reduced with increasing NaCl levels, ECM dependency of seagrape
      seedlings increased. Tissues of ECM plants had significantly increased
      concentrations of P and K but lower Na and Cl concentrations than those of non
      ECM plants. Higher K concentrations in the leaves of ECM plants suggested a
      higher osmoregulating capacity of these plants. Moreover, the water status of ECM
      plants was improved despite their higher evaporative leaf surface. The results
      suggest that the reduction in Na and Cl uptake together with a concomitant
      increase in P and K absorption and a higher water status in ECM plants may be
      important salt-alleviating mechanisms for seagrape seedlings growing in saline
      soils.

PMID- 17033817
TI  - Zinc-tolerant Suillus bovinus improves growth of Zn-exposed Pinus sylvestris
      seedlings.
AB  - Scots pine (Pinus sylvestris L.) seedlings inoculated or not (NM) by a Zn
      sensitive or a Zn-tolerant isolate of the ectomycorrhizal fungus Suillus bovinus
      (L. Fr.) Roussel were exposed to 0.1 or 150 muM Zn(2+) for 9 months. We
      hypothesized that inoculation with a Zn-tolerant S. bovinus isolate should result
      in added Zn resistance of the host plant. Plant and fungal growth as well as
      nutrient profiles and photosynthetic pigments in pine needles were quantified. In
      NM plants and in plants colonized by the Zn-sensitive isolate, plant growth, N,
      P, Mg and Fe assimilation were strongly inhibited under Zn stress and concurred
      with significantly reduced chlorophyll concentrations. In contrast, plants
      colonized by the Zn-tolerant isolate grew much better and remained
      physiologically healthier when exposed to elevated Zn. These results provide
      further evidence for the important role metal-adapted mycorrhizal fungi play as
      an effective biological barrier against metal toxicity in trees.

PMID- 17033818
TI  - Cytoplasmic Clb2 is required for timely inactivation of the mitotic inhibitor
      Swe1 and normal bud morphogenesis in Saccharomyces cerevisiae.
AB  - Subcellular localization is an important determinant of substrate and functional
      specificity for cyclin-cyclin dependent kinase (CDK) complexes. This work
      addresses the cytoplasmic function of the budding yeast mitotic cyclin Clb2,
      which is mostly nuclear but is also present in the bulk cytoplasm and at the
      mother-bud neck. Clb2 contains two leucine-rich nuclear export signals (NESs)-
      one of which we newly describe here--that maintain its presence in the cytoplasm.
      Yeast strains bearing mutations in one or both of these NESs have elongated buds,
      indicative of a G2/M cell cycle delay. A small number of these cells exhibit a
      filamentous-like morphology under conditions that do not normally induce
      filamentous growth. These phenotypes are enhanced by deletion of the other three
      mitotic cyclins (CLB1,3,4) and are dependent on expression of Swe1, the yeast
      Cdk1 inhibitory kinase. Deltaclb1,3,4 Deltabud3 cells, which fail to localize
      Clb2 to the bud neck, also exhibit a Swe1-dependent elongated bud phenotype. Our
      results support a model in which cytoplasmic Clb2-Cdk1 is required for timely
      inactivation of Swe1 at the G2/M transition and bud neck targeting of Clb2
      contributes to the efficiency of this process. Cytoplasmic Clb2 may also be
      important for repression of filamentous growth.

PMID- 17033819
TI  - RNA editing site recognition in heterologous plant mitochondria.
AB  - RNA editing is a process that modifies the information content of mitochondrial
      messenger RNAs in flowering plants changing specific cytosine residues into
      uridine. To gain insight into editing site recognition, we used electroporation
      to introduce engineered wheat (Triticum aestivum) or potato (Solanum tuberosum)
      mitochondrial cox2 genes, and an atp9-containing chimeric gene, into non-cognate
      mitochondria, and observed the efficiency of editing in these contexts. Both
      wheat and potato mitochondria were able to express "foreign" constructs, and
      their products were properly spliced. Seventeen and twelve editing sites are
      present in the coding regions of wheat and potato cox2 transcripts, respectively.
      Eight are common to both plants, whereas nine are specific to wheat, and four to
      potato. An analogous situation is found for the atp9 mRNA coding regions from
      these species. We found that both mitochondria were able to recognize sites that
      are already present as T at the genomic level, making RNA editing unnecessary for
      that specific residue in the cognate organelle. Our results demonstrate that non
      cognate mitochondria are able to edit residues that are not edited in their own
      transcripts, and support the hypothesis that the same trans-acting factor may
      recognize several editing sites.

PMID- 17033820
TI  - Mitochondrial haplogroup N9b is protective against myocardial infarction in
      Japanese males.
AB  - Superoxide, which mitochondria mainly produce in vascular endothelial cells,
      plays an important role in the pathogenesis of atherosclerosis and coronary
      artery disease. Accordingly, mitochondrial functional differences are thought to
      be one of the most important factors for the risk of myocardial infarction among
      various individuals. In the present study, we surveyed mitochondrial haplogroups
      associated with myocardial infarction in Japanese subjects. The study population
      comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a
      first myocardial infarction (920 males, 261 females) and the control subjects
      (522 males, 434 females). Twenty-eight mitochondrial single nucleotide
      polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2,
      M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and
      fluorescent beads combined with sequence-specific oligonucleotide probes. After
      adjustment for age, sex, body mass index, and prevalence of smoking,
      hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P =
      0.0019) lower prevalence of haplogroup N9b was detected in subjects with
      myocardial infarction than in the controls. Especially, the prevalence of this
      haplogroup was significantly lower (P = 0.0007) in the male subjects with the
      disease than in the male controls. In contrast, there were trends towards higher
      prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant
      haplogroup-related associations were detected for females. Our data suggest that
      haplogroup N9b confers resistance against myocardial infarction in Japanese
      males.

PMID- 17033821
TI  - An improved RT-PCR method for the detection of killer-cell immunoglobulin-like
      receptor (KIR) transcripts.
AB  - Killer cell immunoglobulin-like receptors (KIRs) are expressed on human natural
      killer (NK) cells and a proportion of T cells. As the specificity of these NK and
      T cells is, at least in part, determined by the combination of KIRs they express,
      it is important to be able to determine the KIR expression pattern of NK and T
      cell clones to understand their function. However, for most KIR genes, specific
      reagents to detect expression are currently either unavailable or sensitive to
      allelic variations. In this study, a reverse transcriptase-polymerase chain
      reaction (RT-PCR) that uses new primer sets for the gene-specific detection of
      KIR transcripts is presented and validated. The key advantage of this RT-PCR
      method over previously published ones is that it was designed to detect
      transcripts of all confirmed allelic variants of the KIR genes, while remaining
      gene-specific.

PMID- 17033822
TI  - Association of interferon-gamma gene haplotype in the Chinese population with
      hepatitis B virus infection.
AB  - In general, cytokines encoded by different genes of human genome might strongly
      influence host cell-mediated immune responses, which play an important role in
      the clearance of virus by the infected host. Interferon gamma (IFN-gamma)
      produced by T lymphocytes and natural killer cells plays an essential role in
      affecting cellular immune responses. A functional study demonstrated that two
      single nucleotide polymorphisms located in the IFN-gamma gene intron (at
      positions +874 and +2109) were involved in its transcriptional regulation. The
      aim of this study was to evaluate whether IFN-gamma gene polymorphisms or its
      haplotypes might be associated with predisposition to hepatitis B virus (HBV)
      infection in the Chinese population. The study included 181 cases with HBV
      infection and 272 gender, age-matched healthy controls. All genotyping were
      identified by polymerase chain reaction in association with the measurement of
      amplification refractory mutation system. A significant difference was observed
      between case and control groups. The frequency of +874A allele was significantly
      higher in patients than in controls (OR = 2.25, 95%CI = 1.69-2.99, P < 0.0001).
      However, no significant difference was found in the allelic frequencies of IFN
      gamma +2109A/G between cases and controls (P > 0.05). By haplotype analysis, the
      frequency of haplotype AG (+874A and +2109G) revealed a significant difference in
      the cases in comparison to controls (P < 0.0001). Multiple logistic regression
      analysis showed that individuals possessing haplotype AG had an increased
      likelihood of HBV infection (OR = 8.14, 95%CI = 4.98-13.30). Our results suggest
      that haplotype AG containing +874A and +2109G may be a crucial risk factor of
      genetic susceptibility to HBV infection in the Chinese population.

PMID- 17033823
TI  - Genetic variants of the IgA Fc receptor (FcalphaR, CD89) promoter in chronic
      hepatitis C patients.
AB  - Fc receptor for IgA (FcalphaR, CD89) is capable of triggering IgA-mediated immune
      responses to pathogens and has been proposed to function in circulating IgA
      clearance. Because inheritable variations modifying individual immune responses
      or immunoglobulin catabolism may affect the chronicity of viral infection, we
      investigated whether promoter polymorphisms of the FcalphaR gene (FCAR) affect
      chronic hepatitis C virus (HCV) infection and its disease progression. The two 
      311T/C and -142T/C single-nucleotide polymorphisms (SNPs) were studied by direct
      DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both 
      311CC and -142CC genotypes were more frequent in CHC patients (15.9 and 18.6%)
      compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) =
      3.10, 95% confidence interval CI) = 1.53-6.30 and p = 0.014, OR = 2.06, 95% CI =
      1.14-3.72, respectively], and were associated with infection with HCV genotype
      2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, -311CC and -142CC were
      decreased in 59 patients at advanced stages of disease as assessed on the basis
      of hepatic fibrosis markers such as decreased platelet count (PLT) (<
      150,000/microl) (5.1 and 8.5%) compared with 91 patients with normal PLT (> or =
      150,000/microl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively).
      Moreover, among the patients with normal PLT (but not with decreased PLT), -311CC
      or -142CC was significantly associated with decreased serum IgA levels (p = 0.023
      or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs
      may be related to chronic HCV infection and disease progression in Japanese CHC,
      which might be explained by altered FcalphaR expression affecting IgA-mediated
      immune responses and/or IgA catabolism.

PMID- 17033824
TI  - Mhc class I genes of the cichlid fish Oreochromis niloticus.
AB  - In terms of number of species, perciform (perch-like) fishes are one of the most
      diversified groups of modern vertebrates. Within this group, the family Cichlidae
      is best known for its spectacular adaptive radiation in the great lakes of East
      Africa. The molecular tool kit used in the study of this radiation includes the
      major histocompatibility complex (Mhc) genes. To refine this tool, information
      about the organization of the Mhc regions is badly needed. In this study, the
      first step was taken toward providing such information for the Mhc class one
      regions of Oreochromis niloticus, a representative species of the tilapiine
      branch of the Cichlidae, for which good bacterial artificial chromosome library
      is available. Screening of the library with class I gene probes led to the
      identification and isolation of 31 class-I-positive clones. Sequencing of one of
      these clones and partial characterization of the remaining clones for the
      presence of class I exons resulted in the construction of two contigs
      representing the class I region of this species as well as identification of
      seven additional class-I-positive singleton clones. The O. niloticus genome was
      shown to contain at least 28 class I genes or gene fragments. The shorter of the
      two contigs was approximately 330 kb long and contained eight class I genes/gene
      fragments; the longer contig encompassed 1,200 kb of sequence and contained
      minimally 17 class I genes/gene fragments; three additional class I genes were
      found to be borne by a clone that might be part of the shorter contig.

PMID- 17033825
TI  - Production of soft rot resistant calla lily by expressing a ferredoxin-like
      protein gene (pflp) in transgenic plants.
AB  - An efficient protocol for the Agrobacterium tumefaciens-mediated transformation
      of calla lily (Zantedeschia elliottiana (W. Wats.) Engl. cultivar 'Florex Gold')
      is described. Shoot basal discs were co-cultivated with A. tumefaciens C58C1
      carrying a plasmid containing neomycin phosphotransferase (nptII) and plant
      ferredoxin-like protein (pflp) genes. After Agrobacterium co-cultivation, the
      shoot basal discs were exposed to 100 mg l(-1) kanamycin for selection. Twenty
      eight out of 260 discs (10.8%) were found to have survived and produced shoot
      clusters. Twenty-six of these were confirmed to contain the pflp transgene by
      PCR, ending up in 10% transformation efficiency. The disease resistance
      investigation revealed that 18 transgenic plants exhibited resistance to soft rot
      disease caused by Erwinia carotovora subsp. carotovora. The presence of pflp gene
      was demonstrated by PCR, and its accumulation and activity was confirmed by
      Western blot and disease resistance assay. This was the first report to show the
      successful transformation and resistance to a bacterial pathogen in Zantedeschia.
      The protocol is useful for the quality improvement of calla lily through genetic
      transformation.

PMID- 17033826
TI  - The effects of dietary phosphorus deficiency on surface pH and membrane
      composition of the mucosa epithelium in caprine jejunum.
AB  - In ruminants, the uptake of inorganic phosphate (P(i)) across the intestinal
      mucosa epithelium by Na-dependent and Na-independent mechanisms is a main
      regulatory factor in P homeostasis. The aim of the study was to elucidate to
      which extent Na-independent mechanisms, including pH effects or composition of
      mucosal brush-border membranes, could be involved in positive stimulation of P(i)
      absorptive processes seen under the P deficient condition. Therefore, luminal,
      surface and intracellular pH of the jejunal epithelial cells in control and P
      depleted goats were compared and biochemical analyses of membrane phospholipids
      in the apical membrane of the jejunal epithelium were performed. Dietary P
      depletion resulted in decreased plasma P(i) levels. While pH in jejunal ingesta
      was not significantly changed, P depletion resulted in a significantly lower
      surface pH in the crypt region compared to control animals (7.62 +/- 0.02 vs.
      7.77 +/- 0.04, n = 4, P < 0.01). Inhibition of apical Na(+)/H(+)-exchange
      resulted in an increase of the jejunal surface pH in P depleted animals by 0.07
      +/- 0.01 (n = 6, P < 0.01) and 0.05 +/- 0.01 (n = 6, P < 0.01) for the villus and
      the crypt region, respectively. This increase were inversely correlated with the
      initial surface pH prior to inhibition. In contrast to surface pH, intracellular
      pH of the jejunal epithelium and the phospholipid composition of the apical
      jejunal membrane were not affected by P depletion. Although the data suggest the
      existence of a Na(+)/H(+)-exchange mechanism at the luminal surface of goat
      jejunum they do not support the hypothesis that adaptational processes of active
      P(i) absorption from goat jejunum in response to low dietary P could be based on
      "non P(i) transporter events".

PMID- 17033827
TI  - Interactions of human tenascin-X domains with dermal extracellular matrix
      molecules.
AB  - Tenascin-X (TNX) is a large 450 kDa extracellular matrix protein expressed in a
      variety of tissues including skin, joints and blood vessels. Deficiency of TNX
      causes a recessive form of Ehlers-Danlos syndrome characterized by joint
      hypermobility, skin fragility and hyperextensible skin. Skin of TNX deficient
      patients shows abnormal elastic fibers and reduced collagen deposition. The
      mechanism by which TNX deficiency leads to connective tissue alterations is
      unknown. Here we report that C-terminal domains of human TNX bind to major dermal
      fibrillar collagens and tropoelastin. We have mapped these interactions to the
      fibronectin type III repeat 29 (FNIII29) and the C-terminal fibrinogen domain
      (FbgX) of TNX. In addition we found that FNIII29 of TNX accelerates collagen
      fibrillogenesis in vitro. We hypothesize that TNX contributes to matrix stability
      and is possibly involved in collagen fibril formation.

PMID- 17033828
TI  - Effects of unilateral vocal cord paralysis on objective voice measures obtained
      by Praat.
AB  - Unilateral vocal cord paralysis (VCP) affects the objective properties of voice
      by diminished neurologic control and degenerative changes in laryngeal tissue.
      The goal of this study was to compare the acoustic parameters of VCP patients
      with control volunteers using the software Praat. Acoustic analysis results of 18
      unilateral VCP patients were compared with age and sex matched 72 normal adult
      volunteers. Comparison of acoustic analysis results of male and female VCP
      patients with their age and sex matched control groups revealed statistically
      significant difference in jitter, shimmer, and noise-to-harmonics ratio values (P
      < 0.01) in both groups. There were no differences in mean fundamental frequency
      and intensity values. We conclude that these differences were in accordance with
      the results obtained by commercially available voice analysis programs. This
      study reflects the first results obtained with Praat software in VCP patients.
      Using the software Praat, is free and easy, that supports the clinician to rely
      on objective scientific data.

PMID- 17033829
TI  - Idiopathic laryngeal spasm: management and long-term outcome.
AB  - Idiopathic laryngeal spasm (ILS) is an uncommon disorder characterised by brief
      episodes of stridor, occurring at any time. Subsequent outpatient ENT examination
      is normal. These episodes cause considerable anxiety for both patient and
      physician. Little is known about the initiating event(s) in this condition or the
      long-term outcome. Using a combination of telephone and postal questionnaires
      with case note review, we have reviewed a cohort of 21 patients with this
      diagnosis managed by the senior author over the last 15 years. None of the 19
      patients who responded were worse; 13 (68%) described improvement or complete
      resolution of symptoms. ILS is difficult to classify in the spectrum of vocal
      cord disorders, but appears distinct to those previously described. The condition
      responds well to a conservative management approach of reassurance and
      counselling.

PMID- 17033830
TI  - Lymphoscintigraphy and radioguided sentinel node biopsy in oral cavity squamous
      cell carcinoma: same day protocol.
AB  - The routine use of a sentinel node biopsy (SNB) protocol in oral cavity squamous
      cell carcinomas (SCC) has been challenged on the basis of the elevated number of
      sentinel nodes (SNs) detected (>2.5) and on the multiply neck level involvement
      reported in several studies. These data limit the practical application of the
      protocol, because in such cases, it seems easier and safer to perform a selective
      neck dissection. The aim of our study is to perform radioguided surgery 1-3 h
      after lymphoscintigraphy (same day protocol) to detect the lymph nodes closest to
      the tumour site. In our study, 12 patients affected by cT1-2 N0 SCC of the oral
      cavity were submitted to a same day protocol of a lymphoscintigraphic examination
      (1-3 h before surgery) and a radioguided SNB. We used a hand-held gamma probe and
      performed an elective neck dissection on all patients. The SNs were found in all
      cases with 83% localised in the ipsilateral neck in only levels I-II. The mean
      number of SN detected was 2.1, with a mean pathological size of 13.8 mm measured
      on pathological specimen. Metastases were found in 5/12 cases (41.6%), on levels
      I, II and III and all were identified by step serial sectioning and routine H&E
      staining. This study confirms the accuracy of SNB in predicting the presence of
      occult metastases. This protocol is designed to detect SNs, which are almost
      always on neck level I and II, thereby limiting the number of nodes examined and
      the extension of the surgical approach.

PMID- 17033831
TI  - Non-specific immunological determinations in Meniere's disease: any role in
      clinical practice?
AB  - Several studies supported the hypothesis that an autoimmune response may be a
      pathogenetic factor in Meniere's disease occurrence. It has been demonstrated
      that the endo-lymphatic sac has an important role in the immuno-mediated reaction
      and it has also become evident that an immunological mechanism may be involved in
      the development of endo-lymphatic hydrops. The present study was carried out in
      order to analyse the validity of serological non-specific immune tests in
      determining the possible role of immune pathology in 200 Meniere's suffering
      patients. The immune activity was investigated determining the erythrocyte
      sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor,
      the serum immunoglobulin levels by group, the complement levels, the lymphocyte
      sub-populations, the cryoglobulines, the circulating immune complexes (CIC),
      organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein,
      rheumatoid factor, complement fractions and cryoglobulines were either negative
      or non-significant in the considered cohort of Meniere's disease suffering
      patients. On the other hand, in more than half of the sample group high values of
      CIC were found. Data concerning T-lymphocyte sub-population indicates a clear
      increase in T-helper compared to T-cytotoxic cells, with an increase in the
      CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells
      activation complexes. Our present findings show that early activated T
      lymphocytes change and in particular changes occur in the expression of the
      interleukin-2 receptor. Moreover, it seems to be possible to correlate the
      alteration of the immunological tests and the phase of the disease. Present data
      showed that the immunological factor should be considered a relevant element in
      most of the cases of Meniere's disease.

PMID- 17033832
TI  - Skin damage occurs early in systemic lupus erythematosus and independently of
      disease duration in Brazilian patients.
AB  - To determine if skin damage is related to disease duration in Brazilian patients
      with SLE followed in a tertiary reference center through the application of
      standardized damage index (SLICC/ACR-DI). Sixty SLE patients were enrolled in
      this study. Relevant data were obtained through patients' interview, physical and
      laboratory examinations and review of the hospital records. The frequency and the
      different types of organ damage were determined using de SLICC/ACR-DI. Statistics
      were performed through chi-square and Student's t tests. Multivariate regression
      was used to correlate damage with disease duration. Forty-one (68.3%) patients
      presented any type of cumulative organ damage. The skin (35%), renal (23.3%) and
      neuropsychiatric (18.3%) systems were the most frequently involved, followed by
      peripheric vascular, ocular and cardiovascular systems. Non-Caucasoid patients
      and patients with longer disease duration had a slight tendency for greater organ
      damage (P = 0.05). Skin damage occurred independently of disease duration,
      whereas cardiovascular (P = 0.051), peripheral vascular (P = 0.057) and pulmonary
      damage (P = 0.06) had a tendency to occur more frequently in patients with longer
      disease duration. In this study, 68.3% of permanent damage was observed. An
      elevated frequency of skin damage was observed in this population which occurred
      independently of disease duration. Non-Caucasian patients had a tendency to
      present higher scores, but more studies are necessary to determine if ethnic or
      economic factors are involved.

PMID- 17033833
TI  - Pregnancy outcome in idiopathic inflammatory myopathy.
AB  - The aim of our study was to assess the prevalence and outcome of pregnancy in
      idiopathic inflammatory myopathy patients who became pregnant after the onset of
      the disease. Female idiopathic inflammatory myopathy patients (173) were included
      in our study. The patients' charts and clinical data were retrospectively
      analyzed. One hundred and four female idiopathic inflammatory myopathy patients
      had 186 pregnancies, but only nine of these patients (4 polymyositis-PM, 5
      dermatomyositis-DM) became pregnant after the onset of the disease. Nine patients
      with pregnancies after the disease onset had 14 gravidities. Six pregnancies
      resulted in normal deliveries, two ended in prematurity, six ended in abortions
      (two induced abortions). Regarding the four patients (3 PM, 1 DM) with active
      disease at the time of pregnancy, two pregnancies ended in prematurity, four
      ended in spontaneous abortion and one healthy baby delivered. The other five
      patients (2 PM, 3 DM) with the disease in remission had uneventful pregnancies
      and healthy babies were delivered. Treatment was not required during pregnancy in
      case of two dermatomyositis patients with long lasting remission. New onset
      dermatomyositis developed in one patient in her pregnancy's third trimester. The
      mean weight of newborns in the active myositis cases was 2,193 (1,680-2,700) g;
      while in patients with remission was 3,167 (2,800-3,800) g. The active maternal
      disease in idiopathic inflammatory myopathy (IIM) might result intrauterin
      retardation and death. Disease activity in active and new-onset cases could be
      controlled by increasing the dose of corticosteroid.

PMID- 17033834
TI  - Effect of dehydroepiandrosterone on cartilage and synovium of knee joints with
      osteoarthritis in rabbits.
AB  - The aim of this study was to investigate the effects of intra-articular injection
      of dehydroepiandrosterone (DHEA) on cartilage and synovium of knee joints with
      osteoarthritis (OA) in rabbits and the underlying mechanism. Forty rabbits
      underwent unilateral anterior cruciate ligament transaction and were divided into
      two groups. Rabbits were injected with 100 mumol/l DHEA dissolved in the
      dimethylsulphoxide (DMSO) in the knee joints 5 weeks after transaction, once a
      week for 5 weeks. Rabbits injected with DMSO under the same condition were served
      as a control. All rabbits were killed 1 week after the last injection. The knee
      joints were evaluated by gross morphology, histology, and gene expression
      analysis. Gross morphologic inspection and histological evaluation showed that
      the DHEA group appeared less damage in cartilage and synovium as compared with
      the control. Gene expression analysis revealed that the mRNA expression of matrix
      metalloproteinase-3 (MMP-3) in cartilage and synovium decreased significantly in
      the DHEA group and that of tissue inhibitor of metalloproteinase-1 (TIMP-1)
      increased. No significant difference of interleukin-1 beta (IL-1beta) mRNA
      expression was found in the cartilage between two groups while the mRNA
      expression of IL-1beta in the synovium was largely suppressed in the DHEA group.
      The study suggests that DHEA plays a protective role against cartilage
      degradation and synovium inflammation in rabbits with OA. This role may be
      achieved through the regulation of the MMP-3, TIMP-1, and IL-1beta gene
      expression in the cartilage and synovium.

PMID- 17033835
TI  - Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia
      patients.
AB  - The purpose of this study was to investigate the clinical effects of
      balneotherapy in the treatment of Fibromyalgia Syndrome (FMS) and to determine if
      balneotherapy influences serum levels of inflammation markers, IL-1, PGE2 and
      LTB4. 24 primary fibromyalgia female patients diagnosed according to American
      College of Rheumatology criteria were included to the study. Their ages ranged
      between 33 and 55 years. FMS patients were randomly assigned in two groups as,
      group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min bathing, once in a
      day for five days per week. Patients participated in the study for 3 weeks (total
      of 15 sessions) in Denizli. Group 2 did not receive balneotherapy. FMS patients
      were evaluated by tenderness measurements (tender point count and algometry),
      Visual Analogue Scale, Beck's Depression Index, Fibromyalgia Impact
      Questionnaire. Ten healthy women recruited group three as the controls. Serum
      PGE2, LTB4 and IL1-alpha levels were measured in all three groups. The
      biochemical measurements and clinical assessments were performed before and at
      the end of general period of therapy. Statistically significant alterations in
      algometric score, Visual Analogue score, Beck's Depression Index and PGE2 levels
      (P < 0.001), numbers of tender points (P < 0.01) and Fibromyalgia Impact
      Questionnaire score (P < 0.05) were found after the balneotherapy between group 1
      and 2. Mean PGE2 level of FMS patients were higher compared to healthy control
      group (P < 0.0001) and decreased after the treatment period, only in group 1 (P <
      0.05). As in the group 2 and 3, detectable IL-1 and LTB4 measurements were
      insufficient, statistical analysis was performed, only in group 1. After
      balneotherapy IL-1 and LTB4 significantly decreased in group 1 (P < 0.05). In
      conclusion, balneotherapy is an effective choice of treatment in patients with
      FMS relieving the clinical symptoms, and possibly influencing the inflammatory
      mediators.

PMID- 17033836
TI  - Comment on: Schmidt MI, Duncan BB, Vigo A et al (2006) Leptin and incident type 2
      diabetes: risk or protection? Diabetologia 49:2086-2096.

PMID- 17033837
TI  - Common variants in HNF-1 alpha and risk of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor 1-alpha gene (HNF
      1alpha, now known as the transcription factor 1 gene [TCF1]) cause the most
      common monogenic form of diabetes, MODY3, but it is not known if common variants
      in HNF-1a are associated with decreased transcriptional activity or phenotypes
      related to type 2 diabetes, or whether they predict future type 2 diabetes.
      SUBJECTS AND METHODS: We studied the effect of four common polymorphisms
      (rs1920792, I27L, A98V and S487N) in and upstream of the HNF-1alpha gene on
      transcriptional activity in vitro, and their possible association with type 2
      diabetes and insulin secretion in vivo. RESULTS: Certain combinations of the I27L
      and A98V polymorphisms in the HNF-1alpha gene showed decreased transcriptional
      activity on the target promoters glucose transporter 2 (now known as solute
      carrier family 2 [facilitated glucose transporter], member 2) and albumin in both
      HeLa and INS-1 cells. In vivo, these polymorphisms were associated with a modest
      but significant impairment in insulin secretion in response to oral glucose.
      Insulin secretion deteriorated over time in individuals carrying the V allele of
      the A98V polymorphism (n = 2,293; p = 0.003). In a new case-control (n = 1,511
      and n = 2,225 respectively) data set, the I27L polymorphism was associated with
      increased risk of type 2 diabetes, odds ratio (OR) = 1.5 (p = 0.002; multiple
      logistic regression), particularly in elderly (age > 60 years) and overweight
      (BMI > 25 kg/m(2)) patients (OR = 2.3, p = 0.002). CONCLUSIONS/INTERPRETATION:
      This study provides in vitro and in vivo evidence that common variants in the
      MODY3 gene, HNF-1alpha, influence transcriptional activity and insulin secretion
      in vivo. These variants are associated with a modestly increased risk of late
      onset type 2 diabetes in subsets of elderly overweight individuals.

PMID- 17033838
TI  - Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for
      pancreatic islet beta cell dysfunction.
AB  - AIMS/HYPOTHESIS: Prostaglandin E(2) (PGE(2)) is a well-recognised inhibitor of
      glucose-stimulated insulin secretion (GSIS). The aim of this study was to
      investigate the signalling pathway of PGE(2) in beta cell function regulation in
      HIT-T15 cells and isolated rat islets. MATERIALS AND METHODS: mRNA levels of the
      prostaglandin E receptor 3 (Ptger3) were measured by real-time PCR. Western blot
      analysis was used to detect changes in the levels of PTGER3, phosphorylated and
      total Akt, phosphorylated and total forkhead box 'Other' (Foxo). Transient
      transfection and reporter assays were used to measure Foxo transcriptional
      activity. The biological significance of PGE(2) in beta cell function was
      analysed using MTT, flow cytometry and GSIS assays. RESULTS: We found that
      treating HIT-T15 cells with exogenous PGE(2) stimulated Ptger3 gene expression
      specifically, and diminished cAMP generation. These were accompanied by the
      downregulation of Akt and Foxo phosphorylation in HIT-T15 cells and isolated rat
      islets. Moreover, PGE(2) upregulated basal and partially reversed constitutively
      active Akt-inactivated Foxo transcriptional activity. Furthermore, GSIS was
      impaired in PGE(2)-treated HIT-T15 cells and isolated islets. However, the dosage
      used in the above experiments did not affect beta cell viability and apoptosis.
      In addition, insulin-like growth factor 1 (IGF-1) pretreatment reversed the
      effects of PGE(2), and wortmannin treatment abolished the preventive effects of
      IGF-1. CONCLUSIONS/INTERPRETATION: Our observations strongly suggest that PGE(2)
      can induce pancreatic beta cell dysfunction through the induction of Ptger3 gene
      expression and inhibition of Akt/Foxo phosphorylation without impacting beta cell
      viability. These results shed light on the mechanisms of PGE(2) actions in
      pancreatic beta cell dysfunction.

PMID- 17033839
TI  - Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid
      induced skeletal muscle insulin resistance in vitro.
AB  - AIMS/HYPOTHESIS: Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating
      obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty
      acids, the lipid species implicated in mediating insulin resistance, to
      monounsaturated fatty acids. The aim of the present study was to assess the
      molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced
      insulin resistance. METHODS: SCD1 protein was transiently decreased or increased
      in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or
      liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively. RESULTS:
      Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids
      into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and
      phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure
      of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both
      control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in
      triacylglycerol esterification but attenuated ceramide and DAG accumulation and
      protected myotubes from fatty acid-induced insulin resistance.
      CONCLUSIONS/INTERPRETATION: SCD1 protects from cellular toxicity in L6 myotubes
      by preventing excessive accumulation of bioactive lipid metabolites.

PMID- 17033841
TI  - Splenogonadal fusion: a rare cause of testicular enlargement.
AB  - Splenogonadal fusion is a rare congenital abnormality found in boys and girls.
      There is fusion of the developing splenic anlage and the gonadal mesoderm at
      approximately week 5 of intrauterine life. It commonly presents as a testicular
      mass treated with an unnecessary orchidectomy. We report two cases of the
      discontinuous type presenting with testicular swelling and review the literature.

PMID- 17033842
TI  - Multifocal Balamuthia mandrillaris infection in a dog in Australia.
AB  - A 6-year-old male golden retriever, with an 8-month history of seizures and a
      clinical diagnosis of lymphoma in the central nervous system, was (at the owner's
      request) euthanized after signs of respiratory distress and shock developed. Upon
      postmortem examination, the diagnoses of meningoencephalitis and pneumonia were
      made. A histological examination of selected tissues from both the lung and
      central nervous system revealed a severe, acute, multifocal, amoebic, embolic
      pneumonia and a severe, chronic, multifocal, nonsuppurative, amoebic
      meningoencephalitis. Indirect immunofluorescence analysis confirmed the presence
      of trophozoite and cyst stages of Balamuthia mandrillaris. This is the first
      report of B. mandrillaris (which is a free-living amoeba) causing fatal,
      multifocal granulomatous amoebiasis in a dog in Australia.

PMID- 17033843
TI  - The role of gastrin-releasing peptide on conditioned fear: differential cortical
      and amygdaloid responses in the rat.
AB  - RATIONALE: Bombesin (BB), an amphibian peptide, was shown to affect the
      expression of the stress response. However, the physiological role of the
      mammalian counterparts of BB in mediating anxiety and fear responses remain to be
      characterized. OBJECTIVE: This study examined the effects of gastrin-releasing
      peptide (GRP), a mammalian analogue of BB, and its receptor antagonist,
      BW2258U89, on conditioned emotional response (CER), using fear conditioning.
      MATERIALS AND METHODS: The effects of these compounds on contextual and cued fear
      conditioning were assessed after direct bilateral infusions into the prelimbic
      (PrL) cortex, infralimbic (IL) cortex or central nucleus of the amygdala (CeA).
      RESULTS: GRP (300 ng) microinjected into each of the three target nuclei
      significantly reduced freezing to contextual cues. Similarly, in the cued portion
      of CER, GRP administered to the IL cortex significantly reduced freezing.
      Administration of BW2258U89 resulted in dose-dependent and site-specific effects.
      At the IL cortex, the 50 ng dose decreased freezing to both contextual and cued
      fear conditioning. At the CeA, the 300 ng dose also decreased freezing, but at
      the 50 ng dose, it increased contextual freezing. At the PrL cortex, BW2258U89
      did not affect freezing. CONCLUSIONS: These results illustrate that (1) GRP
      system(s) can significantly affect the expression of learned fear, (2) some of
      the relevant brain sites mediating these effects include the PrL, IL and the CeA,
      and (3) such effects may be dependent upon whether responses were evoked by
      environmental contextual fear cues or by specific auditory cues that were
      explicitly paired with an aversive stimulus.

PMID- 17033844
TI  - Serotonin transporter occupancy induced by paroxetine in patients with major
      depression disorder: a 123I-ADAM SPECT study.
AB  - RATIONALE: To assess the paroxetine-induced serotonin transporter (SERT)
      occupancy (SERTocc) using in vivo (123)I-ADAM SPECT. OBJECTIVES: (123)I-ADAM
      SPECT was used to investigate the SERTocc induced by paroxetine in major
      depression disorder (MDD) patients, to compare the SERT availability in drug-free
      MDD patients and healthy volunteers, and to study the relationship between
      paroxetine plasma concentrations (Cp) and SERTocc. MATERIALS AND METHODS:
      Measures of SERT availability by means of (123)I-ADAM SPECT were obtained in ten
      MDD patients before and after 4- to 6-week treatment with paroxetine 20 mg/day.
      (123)I-ADAM SPECT measures of SERT availability from a group of ten previously
      studied age-matched healthy volunteers were used for comparison. The relationship
      between percentages of SERTocc and paroxetine Cp was studied using an E (max)
      model. RESULTS: Mean SERTocc values were 66.4 +/- 9.5% in midbrain, 63.0 +/- 9.6%
      in thalamus, and 61.3 +/- 10.9% in striatum. No significant differences in
      SERTocc were found among these three regions. No significant differences in mean
      SERT availability were found in any region between drug-free MDD patients
      (midbrain = 1.14 +/- 0.15; thalamus = 0.85 +/- 0.13; striatum = 0.70 +/- 0.07)
      and healthy volunteers (midbrain = 1.19 +/- 0.22; thalamus = 0.96 +/- 0.14;
      striatum = 0.67 +/- 0.15). The E (max) model returned a SERTocc(max) = 70.5% and
      a Cp(50) = 2.7 ng/ml. CONCLUSIONS: Using (123)I-ADAM SPECT, treatment with
      paroxetine 20 mg/day leads to more than 60% SERTocc on average in cerebral
      regions with known high SERT density. Data from this study do not support the
      existence of SERT availability differences between drug-free MDD patients and
      healthy volunteers. Finally, the E (max) model is suitable for the study of
      paroxetine Cp relationship to (123)I-ADAM SPECT-measured SERTocc. This approach
      may be useful for pharmacokinetic-pharmacodynamic relationships in drug
      development.

PMID- 17033845
TI  - Hand-held gamma probe or hand-held miniature gamma camera for minimally invasive
      parathyroidectomy: competition, evolution or synergy?

PMID- 17033846
TI  - MIBG-SPECT/CT-angiography with 3-D reconstruction of an extra-adrenal
      phaeochromocytoma with dissection of an aortic aneurysm.

PMID- 17033847
TI  - Potential role of a new hand-held miniature gamma camera in performing minimally
      invasive parathyroidectomy.
AB  - PURPOSE: Sestamibi scans have increased the use of minimally invasive
      parathyroidectomy (MIP) to treat primary hyperparathyroidism (PHPT) when caused
      by a parathyroid single adenoma. The greatest concern for surgeons remains the
      proper identification of pathological glands in a limited surgical field. We have
      studied the usefulness of a new hand-held miniature gamma camera (MGC) when used
      intraoperatively to locate parathyroid adenomas. To our knowledge this is the
      first report published on this subject in the scientific literature. METHODS:
      Five patients with PHPT secondary to a single adenoma, positively diagnosed by
      preoperative sestamibi scans, underwent a MIP. A gamma probe for radioguided
      surgery and the new hand-held MGC were used consecutively to locate the
      pathological glands. This new MGC has a module composed of a high-resolution
      interchangeable collimator and a CsI(Na) scintillating crystal. It has dimensions
      of around 15 cmx8 cmx9 cm and weighs 1 kg. The intraoperative assay of PTH
      (ioPTH) was used to confirm the complete resection of pathological tissue.
      RESULTS: All cases were operated on successfully by a MIP. The ioPTH confirmed
      the excision of all pathological tissues. The MGC proved its usefulness in all
      patients, even in a difficult case in which the first attempt with the gamma
      probe failed. In all cases it offered real-time accurate intraoperative images.
      CONCLUSION: The hand-held MGC is a useful instrument in MIP for PHPT. It may be
      used to complement the standard tools used to date, or may even replace them, at
      least in selected cases of single adenomas.

PMID- 17033848
TI  - Quantification of FDG PET studies using standardised uptake values in multi
      centre trials: effects of image reconstruction, resolution and ROI definition
      parameters.
AB  - PURPOSE: Standardised uptake values (SUVs) depend on acquisition, reconstruction
      and region of interest (ROI) parameters. SUV quantification in multi-centre
      trials therefore requires standardisation of acquisition and analysis protocols.
      However, standardisation is difficult owing to the use of different scanners,
      image reconstruction and data analysis software. In this study we evaluated
      whether SUVs, obtained at three different institutes, may be directly compared
      after calibration and correction for inter-institute differences. METHODS: First,
      an anthropomorphic thorax phantom containing variously sized spheres and
      activities, simulating tumours, was scanned and processed in each institute to
      evaluate differences in scanner calibration. Secondly, effects of image
      reconstruction and ROI method on recovery coefficients were studied. Next, SUVs
      were derived for tumours in 23 subjects. Of these 23 patients, four and ten were
      scanned in two institutes on an HR+ PET scanner and nine were scanned in one
      institute on an ECAT EXACT PET scanner. All phantom and clinical data were
      reconstructed using iterative reconstruction with various iterations, with both
      measured (MAC) and segmented attenuation correction (SAC) and at various image
      resolutions. Activity concentrations (AC) or SUVs were derived using various ROI
      isocontours. RESULTS: Phantom data revealed differences in SUV quantification of
      up to 30%. After application-specific calibration, recovery coefficients obtained
      in each institute were equal to within 15%. Varying the ROI isocontour value
      resulted in a predictable change in SUV (or AC) for both phantom and clinical
      data. Variation of image resolution resulted in a predictable change in SUV
      quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2
      cc), differences of up to 40% were found between high (7 mm) and low (10 mm)
      resolution images. Similar differences occurred when data were reconstructed with
      a small number of iterations. Finally, no significant differences between MAC and
      SAC reconstructed data were observed, except for tumours near the diaphragm.
      CONCLUSION: Standardisation of acquisition, reconstruction and ROI methods is
      preferred for SUV quantification in multi-centre trials. Small unavoidable
      differences in methodology can be accommodated by performing a phantom study to
      assess inter-institute correction factors.

PMID- 17033849
TI  - Multimodal fusion imaging ensemble for targeted sentinel lymph node management:
      initial results of an innovative promising approach for anatomically difficult
      lymphatic drainage in different tumour entities.
AB  - PURPOSE: There are situations where exact identification and localisation of
      sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand
      held gamma probe and vital dye, either a priori or a posteriori. We developed a
      new method using a simultaneous injection of two lymphotropic agents for exact
      topographical tomographic localisation and biopsy of draining SLNs. The purpose
      of this prospective pilot study was to investigate the feasibility and efficacy
      of this method ensemble. METHODS: Fourteen patients with different tumour
      entities were enrolled. A mixture of (99m)Tc-nanocolloid and a dissolved
      superparamagnetic iron oxide was injected interstitially. Dynamic, sequential
      static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was
      performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan
      data sets were fused and evaluated with special regard to the topographical
      location of SLNs. The day after injection, nine patients underwent SLN biopsy
      and, in the presence of SLN metastasis, an elective lymph node dissection.
      RESULTS: Twenty-five SLNs were localised in the 14 patients examined. A 100%
      fusion correlation was achieved in all patients. The anatomical sites of SLNs
      detected during surgery showed 100% agreement with those localised on the
      multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom
      had nodal metastasis. CONCLUSION: Our novel approach of multimodal fusion imaging
      for targeted SLN management in primary tumours with lymphatic drainage to
      anatomically difficult regions enables SLN biopsy even in patients with lymphatic
      drainage to obscure regions. Currently, we are testing its validity in larger
      patient groups and other tumour entities.

PMID- 17033850
TI  - Evaluation of iterative reconstruction (OSEM) versus filtered back-projection for
      the assessment of myocardial glucose uptake and myocardial perfusion using
      dynamic PET.
AB  - PURPOSE: Iterative reconstruction methods based on ordered-subset expectation
      maximisation (OSEM) has replaced filtered backprojection (FBP) in many clinical
      settings owing to the superior image quality. Whether OSEM is as accurate as FBP
      in quantitative positron emission tomography (PET) is uncertain. We compared the
      accuracy of OSEM and FBP for regional myocardial (18)F-FDG uptake and (13)NH(3)
      perfusion measurements in cardiac PET. METHODS: Ten healthy volunteers were
      studied. Five underwent dynamic (18)F-FDG PET during hyperinsulinaemic
      euglycaemic clamp, and five underwent (13)NH(3) perfusion measurement during rest
      and adenosine-induced hyperaemia. Images were reconstructed using FBP and OSEM +/
      an 8-mm Gaussian post-reconstruction filter. RESULTS: Filtered and unfiltered
      images showed agreement between the reconstruction methods within +/-2SD in Bland
      Altman plots of K (i) values. The use of a Gaussian filter resulted in a
      systematic underestimation of K (i) in the filtered images of 11%. The mean
      deviation between the reconstruction methods for both unfiltered and filtered
      images was 1.3%. Agreement within +/-2SD between the methods was demonstrated for
      perfusion rate constants up to 2.5 min(-1), corresponding to a perfusion of 3.4
      ml g(-1) min(-1). The mean deviation between the two methods for unfiltered data
      was 2.7%, and for filtered data, 5.3%. CONCLUSION: The (18)F-FDG uptake rate
      constants showed excellent agreement between the two reconstruction methods. In
      the perfusion range up to 3.4 ml g(-1) min(-1), agreement between (13)NH(3)
      perfusion obtained with OSEM and FBP was acceptable. The use of OSEM for
      measurement of perfusion values higher than 3.4 ml g(-1) min(-1) requires further
      evaluation.

PMID- 17033851
TI  - Tendons in the plantar aspect of the foot: MR imaging and anatomic correlation in
      cadavers.
AB  - OBJECTIVE: The purpose of this anatomic imaging study was to illustrate the
      normal complex anatomy of tendons of the plantar aspect of the ankle and foot
      using magnetic resonance (MR) imaging with anatomic correlation in cadavers.
      DESIGN: Seven fresh cadaveric feet (obtained and used according to institutional
      guidelines, with informed consent from relatives of the deceased) were studied
      with intermediate-weighted fast-spin-echo MR imaging. For anatomic analysis,
      cadaveric specimens were sectioned in 3-mm-thick slices in the coronal and axial
      planes that approximated the sections acquired at MR imaging. RESULTS: The entire
      courses of the tendons into the plantar aspect of the foot were analyzed. The
      tibialis posterior tendon has a complex distal insertion. The insertions in the
      navicular, second, and third cuneiforms bones were identify in all cases using
      axial and coronal planes. A tendinous connection between the flexor hallucis
      longus and the flexor digitorum longus tendons was identified in five of our
      specimens (71%). The coronal plane provided the best evaluation. The peroneus
      longus tendon changes its direction at three points then obliquely crosses the
      sole and inserts in the base of the first metatarsal bone and the plantar aspect
      of the first cuneiform. CONCLUSIONS: MR imaging provides detailed information
      about the anatomy of tendons in the plantar aspect of the ankle and foot. It
      allows analysis of their insertions and the intertendinous connection between the
      flexor hallucis longus and the flexor digitorum longus tendons.

PMID- 17033852
TI  - Ultrasound detects rapid progression of erosive disease in early rheumatoid
      arthritis: a prospective longitudinal study.
AB  - OBJECTIVE: To evaluate and compare sequential ultrasound exams (US) with power
      Doppler (PD) to radiography for the detection of synovitis and erosions in
      patients with early RA. METHODS: Radiographs and US with PD of the hands and feet
      were performed at baseline and 6+/- 2 months afterwards in 21 early RA patients.
      Their mean (range) age was 42.6 (21-81) years and the female/male ratio was 4:3;
      mean disease duration was 9 (1-28) months. Joints assessed were bilateral 2nd and
      5th MCPs, 5th MTPs and the most swollen PIP in each hand, for a total of eight
      joints per patient. Radiographs (PA, lateral and pronated oblique) were read for
      erosions using the method of Sharp/van der Heijde. On US, erosions were defined
      as cortical defects greater than 2 mm in diameter with an irregular floor.
      Synovitis was rated as +1 (increase in joint fluid without synovial hyperemia),
      +2 (mild blood flow), +3 (moderate blood flow), and +4 (severe blood flow). Two
      blinded trained assessors read all images. RESULTS: US detected 15 erosions in 10
      patients at baseline and 31 erosions in 12 patients on follow-up; radiographs
      could detect only one erosion at baseline and five erosions in three patients on
      follow-up. PD detected synovitis in all patients at baseline and on follow-up. Of
      the joints found to have synovitis, 64% were identified as such at baseline and
      38% on follow-up. CONCLUSIONS: Sequential US can determine disease progression in
      patients with early RA. Such data may allow the clinician to treat RA patients
      earlier in the hope of preventing joint damage.

PMID- 17033853
TI  - Comment regarding "Is anterior release effective to increase flexibility in
      idiopathic thoracic scoliosis? Assessment by traction films" (A. Hempfing et
      al.).

PMID- 17033854
TI  - Is anterior release effective to increase flexibility in idiopathic thoracic
      scoliosis? Assessment by traction films.
AB  - With the advent of thoracoscopy, anterior release procedures in adolescent
      idiopathic scoliosis (AIS) have come into more frequent use, however, the
      indication criteria for an anterior release in thoracic AIS are still
      controversial in the literature. To date, few studies have assessed the influence
      on spinal flexibility and no study has so far been able to show a beneficial
      effect on the correction rate as compared to a single posterior procedure. The
      objective of this study was to evaluate the influence of thoracic disc excision
      on coronal spinal flexibility. Six patients (5 females, 1 male) with AIS and a
      mean age of 15.6 years (range 13-20 years) underwent an open anterior thoracic
      release prior to posterior instrumentation. Cotrel dynamic traction along with
      radiographs of the whole spine including traction films were conducted pre- and
      postoperatively and were evaluated retrospectively. The mean preoperative
      thoracic curve was 89.7 degrees +/- 15.4 degrees (range 65 degrees-110 degrees).
      The flexibility rate in Cotrel traction was 22.8 +/- 8.1%. After performance of
      the anterior release the thoracic curve showed a mean increase of coronal
      correction by 5.5 degrees +/- 5.0 degrees as assessed by traction radiographs.
      The flexibility index changed by 6.2 +/- 5.6%. After posterior instrumentation
      the thoracic curve was corrected to a mean of 36.5 degrees +/- 10.1 degrees
      (correction rate 59.6%). Disc excision in idiopathic thoracic scoliosis only
      slightly increased spinal flexibility as assessed by traction films. In our view
      a posterior release with osteotomy of the concave ribs (concave thoracoplasty,
      CTP) is more effective in increasing spinal flexibility. According to our
      clinical experience, an anterior release prior to posterior instrumentation in
      AIS should only be considered in hyperkyphosis, coronal imbalance or massive
      curves.

PMID- 17033855
TI  - Presence of white bile in malignant biliary obstruction is associated with poor
      prognosis: personal preliminary observations.
AB  - OBJECTIVE: The chemical composition and clinical significance of white bile in
      patients with malignant obstructive jaundice were evaluated in a prospective
      study. MATERIALS AND METHODS: 115 consecutive patients with inoperable malignant
      biliary obstruction underwent endoscopic placement of 10 Fr straight, plastic
      biliary stents, Amsterdam-type. Bile was aspirated during the endoscopic
      procedure and a blood sample was taken. Patients were divided into two groups:
      those with white bile and those with yellow bile. The groups were compared for
      decremental fall in bilirubin, cholangitis after stent insertion, and survival.
      RESULTS: Thirty-five patients (15 men, 20 women; mean age 54 years) underwent
      endoscopic drainage for malignant obstruction (29 hilar, 6 distal bile duct).
      Eighteen patients had white bile. Refractory jaundice (p > -0.025) was seen in
      nine (50%) patients with white bile compared with three (17.6%) patients with
      yellow bile; mean difference -42.2 (95% CI [-62.4, -22.0]) and -45.7 (95% CI [
      72.0, -19.4]), respectively. The bilirubin (0.49 mg/L) and bile acid (14.6
      mmol/L) concentrations in white bile were significantly less than bilirubin (41.9
      mg/L) and bile acid (62.2 mmol/L) concentrations in yellow/black bile.
      Cholangitis developed in 66.6% of patients with white bile compared with 35% of
      those with yellow/black bile (OR 3.67: 95% CI [0.74, 19.25]). Kaplan-Meier curves
      showed that median survival was shorter in patients with white bile (36 [23-60]
      vs 75 [35-220] days) (p = 0.004, log rank test), which was significant even after
      adjusting for potential confounders with Cox proportional hazards regression.
      CONCLUSION: White bile is largely devoid of bilirubin and bile acids. The
      presence of white bile was associated with significantly worse survival in
      patients with malignant biliary obstruction.

PMID- 17033857
TI  - Use of a home water filter in the reduction of trihalomethanes and total organic
      halogen in tap water: forty-one samples from Osaka City and surrounding cities of
      Japan in 1999, 2000, and 2004.

PMID- 17033856
TI  - Microbial communities in the world's largest acidic volcanic lake, Kawah Ijen in
      Indonesia, and in the Banyupahit river originating from it.
AB  - A first study was made on the microbial community composition of the Indonesian
      crater lake Kawah Ijen (pH < 0.3) and the Banyupahit-Banyuputih river (pH 0.4
      3.5) originating from it. Culture-independent, rRNA gene-based denaturing
      gradient gel electrophoresis was used to profile microbial communities in this
      natural and ancient, extremely acidic environment. Similarity in community
      profiles of the different sampling locations was low, indicating heterogeneity in
      community composition. Archaea were present at all sampling locations; archaeal
      diversity was low at the most acidic locations and increased at pH >2.6. Bacteria
      were not detected in the water column of the crater lake, but were found at all
      locations along the acidic river. Bacterial diversity increased with increasing
      pH. Eukarya were only present at pH >2.6. Retrieved rRNA gene sequences of
      Bacteria and Archaea were not closely related to known acidophilic species. It is
      concluded that tolerance to extreme acidity in this system is developed most
      extensively among Archaea. The acidity gradient of the Banyupahit-Banyuputih
      river has a clear effect on microbial community composition and biodiversity.

PMID- 17033858
TI  - Serum levels of volatile organic compounds in patients with sick building
      syndrome.

PMID- 17033859
TI  - Smoking and alcohol use in asbestos abatement workers.

PMID- 17033860
TI  - Dechlorination of DDT by electrocatalytic hydrogenolysis.

PMID- 17033861
TI  - Mercury and organomercurial resistance in Rhodotorula rubra: activation of
      glutathione reductase.

PMID- 17033862
TI  - Use of the Nile monitor, Varanus niloticus L (Reptilia: Varanidae), as a
      bioindicator of organochlorine pollution in African wetlands.

PMID- 17033863
TI  - Seasonal variation of microcystin concentration in Lake Chaohu, a shallow
      subtropical lake in the People's Republic of China.

PMID- 17033864
TI  - Alternative water management for controlling simetryn and thiobencarb runoff from
      paddy fields.

PMID- 17033865
TI  - Monitoring phenolic compounds during biological treatment of Kraft pulp mill
      effluent using bacterial biosensors.

PMID- 17033866
TI  - Variation in pesticide concentrations during composting of food waste and fowl
      droppings.

PMID- 17033867
TI  - Pesticide residues in commercial egg samples in Sao Paulo City, Brazil, 2003
      2005.

PMID- 17033868
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in mussels and Gammarus spp.
      from Dongting Lake in People's Republic of China.

PMID- 17033869
TI  - Accumulation of phthalic acid esters in water spinach (Ipomoea aquatica) and in
      paddy soil.

PMID- 17033870
TI  - Comparison of trace metals concentration in PM10 of different locations of
      Lucknow City, India.

PMID- 17033871
TI  - Dominance of algae in Ganga water polluted through fly-ash leaching: metal
      bioaccumulation potential of selected algal species.

PMID- 17033872
TI  - EDTA influences time and concentration dependent cadmium uptake characteristics
      of Indian mustard.

PMID- 17033873
TI  - Heavy metals in urban roadside plants from Amman, Jordan.

PMID- 17033874
TI  - Organotin species in fish and bivalves samples collected from the Egyptian
      Mediterranean coast of Alexandria, Egypt.

PMID- 17033875
TI  - Heavy metals in water and surface sediments in Winam Gulf of Lake Victoria,
      Kenya.

PMID- 17033876
TI  - Uptake of heavy metals by a ciliate, Tachysoma pellionella, isolated from
      industrial effluents and its potential use in bioremediation of toxic wastewater.

PMID- 17033877
TI  - Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte
      chemotactic protein 1 and 3.
AB  - Acyclic nucleoside phosphonates are potent antiviral agents effective against
      replication of DNA viruses and retroviruses including human immunodeficiency
      virus (HIV). In addition to their antimetabolic mode of antiviral action, acyclic
      nucleoside phosphonates also possess immunomodulatory properties. We have shown
      recently that a number of them stimulate secretion of cytokines including
      chemokines RANTES/CCL5 ("regulated upon activation, normal T cell expressed and
      secreted") and MIP-1 alpha/CCL3 (macrophage inflammatory protein-1 alpha) that
      may inhibit entry of HIV in cells. In present experiments we analyzed effects of
      acyclic nucleoside phosphonates on gene expression of other members of the beta
      family of chemokines, monocyte chemotactic proteins (MCPs), which have also been
      implicated in the control of HIV infection. The following compounds differing at
      the type of heterocyclic base, i.e. adenine (A), or 2,6-diaminopurine (DAP), at
      the 6-amino group of the base, and at the N ( 9 )-side chain represented by 9-[2
      (phosphonomethoxy)ethyl] (PME) and 9-[2-(phosphonomethoxy)propyl] (PMP) moieties
      were included in the study: (1) (R)-PMPA, ie. tenofovir, (2) N ( 6 )-cyclopropyl
      (R)-PMPDAP, (3) N ( 6 )-cyclopentyl-(R)-PMPDAP, (4) N ( 6 )-dimethylaminoethyl
      (R)-PMPDAP, (5) N ( 6 )-cyclopentyl-PMEDAP, (6) N ( 6 )-isobutyl-PMEDAP, (7) N (
      6 ) -cyclohexylmetyl-PMEDAP, and (8) N ( 6 ) -cyclooctyl-PMEDAP. These compounds
      are able to activate production of MCP-1 and MCP-3, and none of them influences
      gene expression of MCP-2, and MCP-5. Enhancement of monocyte chemotactic protein
      expression was found to be mediated by transcriptional factor nuclear factor
      kappaB (NF-kappaB).

PMID- 17033878
TI  - Age and gender do not influence the ability to detect respiration by
      photoplethysmography.
AB  - OBJECTIVE: The non-invasive technique photoplethysmography (PPG) can detect
      changes in blood volume and perfusion in a tissue. Respiration causes variations
      in the peripheral circulation, making it possible to monitor breaths using an
      optical sensor attached to the skin. The respiratory-synchronous part of the PPG
      signal (PPGr) has been used to monitor respiration during anaesthesia, and in
      postoperative and neonatal care. Studies addressing possible differences in PPGr
      signal characteristics depending on gender or age are lacking. METHODS: We
      studied three groups of 16 healthy subjects each during normal breathing; young
      males, old males and young females, and calculated the concordance between PPGr,
      derived from a reflection mode PPG sensor on the forearm, and a reference CO(2
      )signal. The concordance was quantified by using a squared coherence analysis.
      Time delay between the two signals was calculated. In this process, we compared
      three different methods for calculating time delay. RESULTS: Coherence values
      >or=0.92 were seen for all three groups without any significant differences
      depending on age or gender (p = 0.67). Comparison between the three different
      methods for calculating time delay showed a correlation r = 0.93. CONCLUSIONS:
      These results demonstrate clinically important information implying the
      possibility to register qualitative PPGr signals for respiration monitoring,
      regardless of age and gender.

PMID- 17033879
TI  - Research in medical education: balancing service and science.
AB  - Since the latter part of the 1990's, the English-speaking medical education
      community has been engaged in a debate concerning the types of research that
      should have priority. To shed light on this debate and to better understand its
      implications for the practice of research, 23 semi-structured interviews were
      conducted with "influential figures" from the community. The results were
      analyzed using the concept of "field" developed by the sociologist Pierre
      Bourdieu. The results reveal that a large majority of these influential figures
      believe that research in medical education continues to be of insufficient
      quality despite the progress that has taken place over the past 2 decades.
      According to this group, studies tend to be both redundant and opportunistic, and
      researchers tend to have limited understanding of both theory and methodological
      practice from the social sciences. Three factors were identified by the
      participants to explain the current problems in research: the working conditions
      of researchers, budgetary restraints in financing research in medical education,
      and the conception of research in the medical environment. Two principal means
      for improving research are presented: intensifying collaboration between PhD's
      and clinicians, and encouraging the diversification of perspectives brought to
      bear on research in medical education.

PMID- 17033880
TI  - Biological control of the size and reactivity of catalytic Pd(0) produced by
      Shewanella oneidensis.
AB  - The interaction between Shewanella oneidensis MR-1 and the soluble metal Pd(II)
      during the reductive precipitation of Pd(0) determined the size and properties of
      the precipitated Pd(0) nanoparticles. Assessment of cell viability indicated that
      the bioreduction of Pd(II) was a detoxification mechanism depending on the Pd(II)
      concentration and on the presence and properties of the electron donor. The
      addition of H(2) in the headspace allowed S. oneidensis to resist the toxic
      effects of Pd(II). Interestingly, 25 mM formate was a less effective electron
      donor for bioreductive detoxification of Pd(II), since there was a 2 log
      reduction of culturable cells and a 20% decrease of viable cells within 60 min,
      followed by a slow recovery. When the ratio of Pd:cell dry weight (CDW) was below
      5:2 at a concentration of 50 mg l(-1) Pd(II), most of the cells remained viable.
      These viable cells precipitated Pd(0) crystals over a relatively larger bacterial
      surface area and had a particle area that was up to 100 times smaller when
      compared to Pd(0) crystals formed on non-viable biomass (Pd:CDW ratio of 5:2).
      The relatively large and densely covering Pd(0) crystals on non-viable biomass
      exhibited high catalytic reactivity towards hydrophobic molecules such as
      polychlorinated biphenyls, while the smaller and more dispersed nanocrystals on a
      viable bacterial carrier exhibited high catalytic reactivity towards the
      reductive degradation of the anionic pollutant perchlorate.

PMID- 17033881
TI  - Nitrogen transformations in stratified aquatic microbial ecosystems.
AB  - New analytical methods such as advanced molecular techniques and microsensors
      have resulted in new insights about how nitrogen transformations in stratified
      microbial systems such as sediments and biofilms are regulated at a microm-mm
      scale. A large and ever-expanding knowledge base about nitrogen fixation,
      nitrification, denitrification, and dissimilatory reduction of nitrate to
      ammonium, and about the microorganisms performing the processes, has been
      produced by use of these techniques. During the last decade the discovery of
      anammmox bacteria and migrating, nitrate accumulating bacteria performing
      dissimilatory reduction of nitrate to ammonium have given new dimensions to the
      understanding of nitrogen cycling in nature, and the occurrence of these
      organisms and processes in stratified microbial communities will be described in
      detail.

PMID- 17033882
TI  - Alcoholic fermentation of carbon sources in biomass hydrolysates by Saccharomyces
      cerevisiae: current status.
AB  - Fuel ethanol production from plant biomass hydrolysates by Saccharomyces
      cerevisiae is of great economic and environmental significance. This paper
      reviews the current status with respect to alcoholic fermentation of the main
      plant biomass-derived monosaccharides by this yeast. Wild-type S. cerevisiae
      strains readily ferment glucose, mannose and fructose via the Embden-Meyerhof
      pathway of glycolysis, while galactose is fermented via the Leloir pathway.
      Construction of yeast strains that efficiently convert other potentially
      fermentable substrates in plant biomass hydrolysates into ethanol is a major
      challenge in metabolic engineering. The most abundant of these compounds is
      xylose. Recent metabolic and evolutionary engineering studies on S. cerevisiae
      strains that express a fungal xylose isomerase have enabled the rapid and
      efficient anaerobic fermentation of this pentose. L: -Arabinose fermentation,
      based on the expression of a prokaryotic pathway in S. cerevisiae, has also been
      established, but needs further optimization before it can be considered for
      industrial implementation. In addition to these already investigated strategies,
      possible approaches for metabolic engineering of galacturonic acid and rhamnose
      fermentation by S. cerevisiae are discussed. An emerging and major challenge is
      to achieve the rapid transition from proof-of-principle experiments under
      'academic' conditions (synthetic media, single substrates or simple substrate
      mixtures, absence of toxic inhibitors) towards efficient conversion of complex
      industrial substrate mixtures that contain synergistically acting inhibitors.

PMID- 17033883
TI  - The value of autonomy in medical ethics.
AB  - This articles assesses the arguments that bioethicists have presented for the
      view that patients' autonomy has value over and beyond its instrumental value in
      promoting the patients' wellbeing. It argues that this view should be rejected
      and concludes that patients' autonomy should be taken to have only instrumental
      value in medicine.

PMID- 17033884
TI  - Primary splenic marginal zone lymphoma with bladder metastases mimicking
      interstitial cystitis.
AB  - We report the case of a 76-year-old patient with a past medical history of low
      grade chronic lymphocytic leukaemia who presented with severe chronic bladder
      symptoms attributed to interstitial cystitis. She underwent cystectomy and ileal
      conduit formation after the failure of all conventional treatment. Bladder
      histopathology revealed primary splenic marginal zone lymphoma. Literature review
      shows the rarity of such non-hematopoietic visceral metastases. This may
      represent the first reported splenic marginal zone lymphoma with bladder
      involvement and highlights the clinical and histological similarities with
      interstitial cystitis.

PMID- 17033885
TI  - Giant unilateral abdominoscrotal hydrocele in an adult: case report.
AB  - Abdominoscrotal hydrocele (ASH) is an apparently highly uncommon clinical entity
      especially in childhood. While hydrocele is among the commonest inguinal anomaly
      in adult, its extreme form ASH is infrequently reported form. ASH consists of two
      large sacs, both abdominal and scrotal, connecting with the inguinal canal.
      Surgical correction is mandatory. We present a 34-year-old man with giant ASH. He
      was treated with excision of hydrocele sac through an inguinal approach.

PMID- 17033886
TI  - Capillary haemangioma of verumontanum: case report and review of the literature.
AB  - A case of 24-year-old male patient with persisting microscopic haematuria is
      described. The endoscopic diagnosis revealed polyp lesion protruding from the
      origin of verumontanum. The histopathologic examination showed capillary
      haemangioma with fibroepitel component containing no prostatic glandular
      structure. The literature was reviewed, the histogenesis and nomenclature was
      discussed.

PMID- 17033887
TI  - Renal angiomyolipoma with malignant transformation, simultaneous occurrence with
      malignity and other complex clinical situations.
AB  - Renal angiomyolipoma is a benign kidney tumor, which is characterized by the
      presence of mature or immature fat tissue, thick-walled blood vessels, and smooth
      muscles. However, there is a rare possibility of transformation to a malignancy.
      This transformation could be toward sarcoma. And also angiomyolipoma could be
      associated with renal adenocarcinoma in the same kidney. The aim of this study is
      to show the association of angiomyolipoma with complex clinical situations such
      as malign transformation, simultaneous occurrence with adenocarcinoma, bilateral
      tumors with tuberous sclerosis or Wunderlich Syndrome. Findings of clinical
      presentation, pathological evaluation, urography, ultrasonography, and
      computerized tomography of 19 patients who were diagnosed angiomyolipoma in our
      clinic during 1994-2003 were examined retrospectively. Our records indicated that
      radical nephrectomy was performed in three cases of angiomyolipoma in which the
      differential diagnosis from adenocarcinoma could not be made and in another case
      of angiomyolipoma, which was associated with adenocarcinoma. Simple nephrectomy
      was performed in four symptomatic angiomyolipoma cases with tumor size larger
      than 4 cm and partial nephrectomy in another case. In one case, renal
      angiomyolipoma was associated with adenocarcinoma in the same kidney. In one
      case, post-operative recurrence of angiomyolipoma developed 7 months after
      nephrectomy. This patient was diagnosed low-grade leiomyosarcoma. Angiomyolipoma
      is regarded as a benign tumor of the kidney; however, it may also show aggressive
      behaviors and rarely transform to sarcoma. It may also exist in the same kidney
      along with adenocarcinoma or sarcoma.

PMID- 17033888
TI  - Digital subtraction angiography and computer assisted image analysis for the
      evaluation of the antiangiogenetic effect of ionizing radiation on tumor
      angiogenesis.
AB  - PURPOSE: The aim of the present study was to evaluate and quantify the
      antiangiogenetic effect of ionizing radiation on tumor angiogenesis using digital
      subtraction angiography (DSA) in conjunction with computer assisted image
      analysis (CAIA). METHODS: Walker 256 carcinosarcoma was inoculated in both glutei
      of 12 Wistar rats. When the tumors reached a diameter of 1.5 cm, local
      irradiation of the right gluteus was performed. The left gluteus of each animal
      served as a control. After 24 hours of irradiation, angiography was performed,
      and images where digitized and subsequently processed. The effect of irradiation
      was observed both in big and small vessels (smaller or greater than 200 microm).
      RESULTS: Irradiated areas of both small and big vessels showed a statistically
      significant reduction in both total vessel area and length. Small vessels showed
      a greater trend toward suppression by irradiation (not statistically
      significant). CONCLUSION: Irradiation had a deleterious effect in both macro- and
      micro-blood supply of a tumor. The use of CAIA enhanced the efficacy of DSA and
      enabled the in vivo identification of the effect of irradiation on various
      caliber vessels as well as the ratios of total length and total area of small and
      big vessels.

PMID- 17033889
TI  - Window technique on circumcision.
AB  - OBJECTIVE: To remove the preputium by using a simple, quick and safe method
      without damaging glans, frenulum and urethra as well as with a good cosmetic
      result. PATIENTS AND METHODS: The procedure, remind the guillotine technique at
      first, but completely different from it. Basically, a long haemostat is applied
      onto preputium and skin and subdermal tissue were incised; a small window is
      opened at dorsal of preputial mucosa and it is excised, while observing glans and
      frenulum. RESULTS: The circumcisions were performed in a quick, safe and pretty
      bloodless way. There was no case with glans amputation, frenulum short cut or
      urethral damage, even if a clamp includes the foreskin with a part of glans or
      excess frenulum unnoticedly. CONCLUSION: This technique is simple, quick,
      relatively bloodless operation with cosmetically good result. Morever it is quite
      safe against to amputation of glans, frenular short cut or urethral fistula
      formation.

PMID- 17033890
TI  - Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign
      DNA in Volvox carteri.
AB  - DNA methylation plays an important role in the gene-silencing network of higher
      eukaryotes. We have analyzed the 21.5-kb maintenance methyltransferase (M-MTase)
      gene, met1, of the multicellular green alga Volvox carteri. The met1 transcript
      was detected only during the period when DNA replication and cell division are
      taking place. It encodes a 238 kDa protein containing eight C-terminal activity
      domains typical of M-MTases, plus upstream DNA-binding domains including the
      ProDom domain PD003757, which experimental analyses in animal systems have
      indicated is required for targeting the enzyme to DNA-replication foci. Several
      insertions of unknown function make Volvox Met1 the largest known member of the
      Met1/Dnmt1 family. Here we also show that several endogenous transposon families
      are CpG-methylated in Volvox, which we think causes them to be inactive. This
      view is supported by the observation that an in vitro CpG-methylated gene
      introduced into Volvox was maintained in the methylated and silent state over
      >100 generations. Thus, we believe that Met1 recognizes and perpetuates the in
      vitro methylation signal, and that the silencing machinery is then able to
      transduce such a methylation-only signal into a stable heterochromatic (and
      silent) state.

PMID- 17033891
TI  - Functional status in the elderly with insomnia.
AB  - BACKGROUND: Insomnia causes psychological distress in the elderly. Besides
      primary insomnia (PI), illness, medications and psychosocial factors contribute
      to development of sleep disorders. Although elderly insomniacs usually complain
      of poorer daytime functioning, it is unknown whether the disorder affects
      capacity to carry out activities. OBJECTIVE: To assess the relationship in the
      elderly between PI, level of physical functioning, depression and anxiety
      symptoms, state of psychological well-being and consumption of
      psychopharmaceuticals. DESIGN: Cross-sectional, observational study. SETTING:
      Populational. SUBJECTS: About 424 non-institutionalized elderly patients.
      METHODS: Subjects were interviewed at public Health Centres or at home. They were
      considered to have PI if DSM-IV criteria were met. The remaining variables
      measured were: depression and anxiety symptoms (The Goldberg's Depression and
      Anxiety Scale), cognitive state (Short Portable Mental Status Questionnaire),
      physical functioning (The Katz Index and the Instrumental Activities of Daily
      Living Scale), life satisfaction (The Philadelphia Geriatric Center Morale
      Scale), health problems, consumption of pharmaceuticals and sociodemographic
      variables. RESULTS: About 34.2% of the elderly admitted to having problems with
      sleep, but only 20.3% (CI: 95%: 16.5-24.1) fulfilled the criteria for PI. The
      existence of an anxiety disorder, a score below the 50th percentile on The
      Philadelphia Geriatric Center Morale Scale (lower life satisfaction) and
      consumption of psychopharmaceuticals were variables associated with insomnia.
      Amongst the most common illnesses reported, only diabetes appeared with
      significantly higher frequency in the elderly with insomnia (24.4% vs. 14.7%) (p
      < 0.05). No statistically significant association was found between insomnia and
      level of dependence in carrying out basic or instrumental activities.
      CONCLUSIONS: Approximately one fifth of the non-institutionalized elderly meet
      the criteria for PI. Those affected present a poorer state of psychological and
      social well-being, although level of autonomy for conducting basic and
      instrumental activities does not appear to be modified by the disorder. The
      existence of an anxiety disorder, low life satisfaction and consumption of
      psychopharmaceuticals constitute variables associated with PI in the population
      we studied.

PMID- 17033892
TI  - Personality traits and health-related quality of life in patients with mood and
      anxiety disorders.
AB  - BACKGROUND: Health-related quality of life (HRQL) is an accepted outcome measure
      in patients with mood and anxiety disorders. Yet, surprisingly little attention
      has been paid to the determinants. In this paper we test the hypothesis that it
      is associated with personality traits while controlling for mental disorders.
      METHODS: A large sample of outpatients (n = 640) with mood and anxiety disorders
      was studied. The empirically supported five factor model of normal personality
      traits was assessed using the NEO-FFI and includes: neuroticism, extraversion,
      openness to experience, agreeableness, and conscientiousness. Mental disorders
      were assessed with the CIDI, and HRQL with the SF-36. RESULTS: Regression
      analyses revealed that the NEO-FFI scores, with the exception of
      conscientiousness, were significantly associated with SF-36 subscales and summary
      scores, independently from the mental disorders. The percentage of explained
      variance due to the personality traits was highest for the subscales Vitality
      (10.0%), Mental Health (13.3%) and the Mental Health Summary Score (9.5%).
      Furthermore, specific personality traits were related to specific SF-36
      subscales. CONCLUSIONS: A low HRQL of patients with mood or anxiety disorders is
      not only determined by the disease or the current health but is also shaped by
      personality traits that are relatively stable throughout an individual's life
      time.

PMID- 17033894
TI  - What does quality of life mean to older frail and non-frail community-dwelling
      adults in the Netherlands?
AB  - Quality of life is a commonly used but seldom defined concept and there is no
      consensus on how to define it. The aim of this study was to explore the meaning
      of quality of life to older frail and non-frail persons living in the community.
      Qualitative interviews were conducted with 25 older men and women. The audio
      taped interviews were transcribed and coded for content and analyzed using the
      grounded-theory approach. Five themes emerged: (physical) health, psychological
      well-being, social contacts, activities, and home and neighborhood. Factors that
      influenced quality of life were having good medical care, finances and a car.
      Respondents compared themselves mostly to others whose situation was worse than
      their own, which resulted in a satisfactory perceived quality of life. However,
      the priorities of the domains of quality of life were observed to change.
      Moreover, the health of the frail limited the amount and scope of activities that
      they performed. This led to a lower quality of life perceived by the frail
      compared to the non-frail.

PMID- 17033893
TI  - Health-related quality of life after laparoscopically assisted vaginal
      hysterectomy: is uterine weight a major factor?
AB  - OBJECTIVE: To assess uterine size, symptom severity, and hemoglobin level as
      determinants of health-related quality of life (HRQOL) in women subsequently
      undergoing laparoscopically assisted vaginal hysterectomy (LAVH). METHODS: Sixty
      one consecutive women with uterine leiomyoma or adenomyosis undergoing LAVH were
      studied using a prospective cohort design. The Chinese version of the Uterine
      Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire was assessed
      preoperatively. The Taiwan brief version of the World Health Organization Quality
      of Life (WHOQOL-BREF) questionnaire and a self-assessment of the perceived health
      status were assessed preoperatively and 1 day, 1 week, 12 weeks, and 18 months
      postoperatively. RESULTS: Women with a greater uterine weight did not report a
      greater severity of symptoms than those with lower uterine weight. Women with
      more severe symptoms had lower preoperative hemoglobin levels and were usually
      younger. Their perceived health status and their scores in physical domain of
      WHOQOL-BREF were also significantly lower, indicating a poorer HRQOL. The mixed
      effects model found that a normal (higher) baseline hemoglobin level and a
      greater symptom severity were associated with a significant improvement of HRQOL
      in the physical domain of WHOQOL-BREF following LAVH. CONCLUSIONS: Preoperative
      symptom severity, but not uterine weight, was associated with long-term
      improvement in HRQOL after LAVH. Women with severe symptoms could be considered
      for LAVH before development of anemia.

PMID- 17033895
TI  - Are factors associated with subjective quality of life in people with severe
      mental illness consistent over time?--A 6-year follow-up study.
AB  - OBJECTIVE: To investigate the cross-sectional relationship between subjective
      quality of life and sociodemographic clinical and social factors over three
      points of assessment during a 6-year follow-up, and to investigate longitudinal
      predictors of subjective quality of life. METHOD: We investigated a sample of
      people with severe mental illness (n = 92), mainly with a psychosis diagnosis, at
      baseline and at an 18-month and 6-year follow-up. Measures included the
      Lancashire quality of life profile, Manchester short assessment of quality of
      life, Symptom Check List 90, Camberwell Assessment of Needs and the Interview
      Schedule for Social Interaction. RESULTS: Cross-sectionally subjective quality of
      life was associated to self-reported symptoms, social network and unmet needs.
      However, these determinants varied in importance between points of assessment.
      Longitudinal predictors of subjective quality of life were changes in self
      reported symptoms and social network. CONCLUSION: There was a rather consistent
      set of determinants of subjective quality of life over time. Social network seems
      to be an important factor with relevance for improvements in subjective quality
      of life, however largely overlooked in earlier studies within the field.

PMID- 17033896
TI  - Recovered? Association between self-perceived recovery and the SF-36 after minor
      musculoskeletal injuries.
AB  - OBJECTIVE: Recovery after minor musculoskeletal injuries is often
      disproportionately protracted. Our aim was to relate Short Form-36 (SF-36), to
      self-perceived recovery assessed with the question" Do you feel recovered". We
      hypothesized that restitution of physical factors would be reported at least as
      often as improvement of symptoms or impairments and that social and mental
      factors would dominate over physical as determinants for recovery. We followed
      318 patients with minor traffic-related injuries for up to 6 months. RESULTS: For
      all SF-36 subscores more than 60% of the recovered patients had returned to their
      pre-injury levels. The subscores with the highest proportions (> 80%) were all
      mainly reflecting disability. For no subscore, however, was the proportion 100%.
      Normalizations in the SF-36 subscores for "Bodily Pain" (BP) (Odds Ratio, OR =
      7.2), "Role limitations due to physical function" (OR = 5.3) were associated with
      self-perceived recovery. CONCLUSION: Abolition of pain appears to be paramount
      for the self-perceived recovery, but it is neither a sufficient nor a necessary
      prerequisite. Contrary to our expectation, physical aspects of functional health
      status were more strongly associated with recovery than were emotional or social
      aspects.

PMID- 17033897
TI  - Negative mood and quality of life in patients with asthma.

PMID- 17033898
TI  - Black-white differences in health-related quality of life among older adults.
AB  - Very little information exists on racial differences in quality of life among
      older adults. In this paper, we examine black-white differences in health-related
      quality of life (HRQOL) and identify factors that may account for these
      differences. The participants were 5,986 community-dwelling persons age 65+ (62%
      black at baseline) from the Chicago Health and Aging Project. Poor HRQOL was
      defined as having 14 or more self-reported physically or mentally unhealthy days
      over the past 30 days. A higher proportion of blacks (11.0%) than whites (9.7%)
      reported poor HRQOL. After adjusting for age and sex, blacks had increased odds
      of reporting poor HRQOL compared with whites (odds ratio [OR] = 1.72; 95% CI:
      1.50-1.98). The black-white differences in HRQOL tended to increase with age (p <
      0.05) and were greater among females (p < 0.05). Lifetime socioeconomic status,
      summary measures of medical conditions, and cognitive function accounted for most
      of the black-white difference (OR = 1.06; 95% CI: 0.89-1.27). Our results suggest
      that racial differences in HRQOL are associated with the combined effects of
      social disadvantage, poor physical health, and lower cognitive function.

PMID- 17033899
TI  - Quality of life of nasopharyngeal carcinoma survivors in Mainland China.
AB  - The aim of this study is to evaluate the quality of life (QoL) of nasopharyngeal
      carcinoma (NPC) survivors. 192 NPC survivors treated in 1999 and 2000 were
      enrolled in this study. Median follow up was 3.6 years (range 2.4-4.6 years). The
      Chinese SF-36 questionnaire and a self-reported symptom checklist consisting of
      14 items were completed at clinics. Sociodemographic factors and clinical
      information were also collected. Most functional domains of the Chinese SF-36
      were significantly worse in NPC survivors compared to the normal population.
      Xerostomia, hearing loss, hypomnesia, dysphagia, and trismus were frequently
      reported symptoms. Sociodemographic variables including gender, age, dialect,
      educational level, monthly income, economic status, and number of comorbidities
      were univariate predictors of different SF-36 domains and symptoms. Patients with
      earlier T and N stage, irradiated by linear accelerator, with lower dose and
      weekly dose to nasopharynx and neck, and those who had anterior nasal radiation
      field reported better QoL. Multiple stepwise regression analysis showed that the
      number of comorbidities, monthly income, age, and T stage were independent
      factors affecting global QoL. We concluded that NPC survivors had worse QoL than
      the normal population and improving radiotherapy might increase physical and
      functional domain of QoL.

PMID- 17033900
TI  - Once-daily sublingual allergen-specific immunotherapy improves quality of life in
      patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind,
      randomised study.
AB  - The effect of sublingual immunotherapy on quality of life (QoL) was examined in
      patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were
      randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T
      Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks
      before the start of the grass pollen season and continued throughout. If symptoms
      were present, patients received loratadine or placebo rescue medication. There
      were three major findings: in patients using loratadine, grass allergen tablets
      provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life
      Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with
      75,000 SQ-T tablet than with placebo at first and second seasonal visit,
      respectively; in patients not using loratadine, grass allergen tablets improved
      QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T
      tablet at second seasonal visit; grass tablets (without loratadine) had a greater
      effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with
      75,000 SQ-T tablets than loratadine at second seasonal visit. These data show
      that sublingual immunotherapy with grass allergen tablets improves QOL in
      allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater
      than rescue antihistamine alone.

PMID- 17033901
TI  - Minimally important change determined by a visual method integrating an anchor
      based and a distribution-based approach.
AB  - BACKGROUND: Minimally important changes (MIC) in scores help interpret results
      from health status instruments. Various distribution-based and anchor-based
      approaches have been proposed to assess MIC. OBJECTIVES: To describe and apply a
      visual method, called the anchor-based MIC distribution method, which integrates
      both approaches. METHOD: Using an anchor, patients are categorized as persons
      with an important improvement, an important deterioration, or without important
      change. For these three groups the distribution of the change scores on the
      health status instrument are depicted in a graph. We present two cut-off points
      for an MIC: the ROC cut-off point and the 95% limit cut-off point. RESULTS: We
      illustrate our anchor-based MIC distribution method determining the MIC for the
      Pain Intensity Numerical Rating Scale in patients with low back pain, using two
      conceivable definitions of minimal important change on the anchor. The graph
      shows the distribution of the scores of the health status instrument for the
      relevant categories on the anchor, and also the consequences of choosing the ROC
      cut-off point or the 95% limit cut-off point. DISCUSSION: The anchor-based MIC
      distribution method provides a general framework, applicable to all kind of
      anchors. This method forces researchers to choose and justify their choice of an
      appropriate anchor and to define minimal importance on that anchor. The MIC is
      not an invariable characteristic of a measurement instrument, but may depend,
      among other things, on the perspective from which minimal importance is
      considered and the baseline values on the measurement instrument under study. A
      balance needs to be struck between the practicality of a single MIC value and the
      validity of a range of MIC values.

PMID- 17033902
TI  - Testing relationships between clinical and non-clinical variables in xerostomia:
      a structural equation model of oral health-related quality of life.
AB  - OBJECTIVES: The aim of the study was to systematically test Wilson and Cleary's
      [Wilson IB, Cleary PD. JAMA 1995; 273: 59-65] conceptual model of the direct and
      mediated pathways between clinical and non-clinical variables in relation to the
      oral health-related quality of life (OHRQoL) of patients with xerostomia.
      METHODS: We collected measures of clinical variables, self-reported symptoms,
      OHRQoL, global oral health perceptions and subjective well-being from 85 patients
      attending outpatient clinics. RESULTS: Structural equation modelling indicated
      support for the dominant direct pathways between the main levels of the model;
      more severe clinical signs predicted worse patient reported symptoms; worse
      symptom perception was associated with a lower functional status as measured by
      OHRQoL; and lower OHRQoL predicted worse global oral health perceptions. There
      was no relationship between the final two levels of the model; global oral health
      perceptions and subjective well-being. Subjective well-being was associated
      instead with earlier non-adjacent levels; biological variables, symptoms and
      functional status. These pathways were both direct (salivary flow-well-being,
      functioning-well-being) and indirect (clinical signs-well being, symptom status
      well-being). There were also indirect pathways; most notably, the impact of
      clinical variables on OHRQoL was mediated by patient reported symptom status.
      CONCLUSIONS: The results support Wilson and Cleary's conceptual model of patient
      outcomes as applied to a chronic oral health condition and highlight the
      complexity of (inter)relationships between key clinical and non-clinical
      variables. Further conceptual development of the model is discussed, particularly
      the role of individual difference factors, and theoretical and methodological
      issues in OHRQoL research are highlighted.

PMID- 17033903
TI  - Quality of life, health status and clinical outcomes in Type 2 diabetes patients.
AB  - This study examines relationships between patient reported outcomes (PROs) and
      clinical outcomes in Type 2 diabetes mellitus (T2DM). Patients at the outpatient
      clinics of a university hospital completed measures of generic health status (SF
      12), diabetes-specific quality of life (Audit of Diabetes Dependent Quality of
      Life - ADDQoL), and depressive symptoms (Center for Epidemiologic Studies
      Depression - CES-D). Patient reported data were merged with a retrospective
      collection of clinical and utilization data, including HbA1C, from electronic
      medical records. A Charlson comorbidity score, diabetes complications score, BMI,
      and total number of ER and hospital visits were calculated. Usable response rate
      was 44.3% (n = 385). Patients were dichotomized into glycemic control levels
      based on the ADA recommended A1C level < 7.0, vs. >or= 7.0. The ADDQoL, PCS-12,
      and MCS-12 scores were separately examined as dependent variables using
      hierarchical regression models, with glycemic control as the primary explanatory
      variable, and controlling for demographics and clinical variables including
      comorbidities and complications. Glycemic control was not a significant predictor
      in any regression model. Obesity was a significant predictor leading to poorer
      PCS-12 and MCS-12 scores, while depressive symptoms significantly resulted in
      lower PCS-12, MCS-12 and ADDQoL scores. These and other factors related to self
      management behaviors may contribute to a greater understanding of how to
      intervene with patients with T2DM. The use of such PROs alongside biomedical
      measures such as A1C is recommended.

PMID- 17033904
TI  - Quality of life of mental health consumers in Hong Kong: Analysis of service
      perceptions.
AB  - OBJECTIVES: Successful psychiatric rehabilitation entails fostering overall
      quality of life of individuals recovering from severe mental illnesses.
      Understanding how service-related perceptions may be related to quality of life
      can be useful in improving the effectiveness of community-based care. This study
      investigated the quality of life of mental health consumers using a service
      oriented paradigm. METHODS: 162 mental health consumers from community-based
      psychiatric rehabilitation centers were interviewed. Analyses were conducted to
      investigate the relationships between service perceptions (perceived treatment
      coercion, rehabilitation needs, and continuity of care) and quality of life.
      RESULTS: Physical health quality was negatively related to rehabilitation needs.
      Mental health quality was negatively related to both rehabilitation needs and
      poorer continuity of service. Life satisfaction was negatively related to poorer
      continuity of service and higher perceived treatment coercion. CONCLUSIONS: This
      study highlighted the significance of service perceptions in the well-being of
      individuals with severe mental illness.

PMID- 17033905
TI  - Validation of the asthma impact survey, a brief asthma-specific quality of life
      tool.
AB  - BACKGROUND: The Asthma Impact Survey (AIS-6) is a new six question asthma outcome
      tool for which information on validity has not been published. OBJECTIVE: To
      provide validation for the AIS-6 as a brief asthma-specific quality of life tool.
      METHODS: Surveys were sent to a random sample of members of a large managed care
      organization who were at least 35 years of age and in the two-year period
      preceding the survey had either (1) at least one documented asthma-related
      medical encounter, or (2) at least a 6 months supply of asthma medication
      dispensed. In addition to the AIS-6, the survey included a validated quality of
      life tool [the mini-Asthma Quality of Life Questionnaire (AQLQ)]; a validated
      asthma control questionnaire [the Asthma Therapy Assessment Questionnaire
      (ATAQ)]; a validated symptom severity scale (AOMS); and information regarding
      demographics, co-morbidities, asthma severity, and asthma management. The results
      of the AIS-6 were compared to the results of the other tools by means of
      correlation and factor analysis. Independent predictors of AIS-6 and AQLQ scores
      were determined by multiple stepwise linear regression analyses. RESULTS: AIS-6
      scores were significantly related to female sex, educational level, income,
      smoking, body mass index (BMI), COPD, steroid use, and hospitalization history in
      bivariate analyses. The AIS-6 score significantly correlated (r = - 0.84, p <
      0.0001) with the AQLQ total score and loaded on the three factors (activity,
      symptoms, and concern/bother) reflected by the survey information and on which
      the AQLQ also loaded. Significant but somewhat smaller correlations were found
      between the AIS-6 and the ATAQ (r = 0.70, p < 0.0001) and the AOMS (r = 0.55, p <
      0.0001). Independent predictors were the same for the AIS-6 and AQLQ and included
      oral steroid use, COPD history, BMI, female sex, educational level, and
      hospitalization in the past year. CONCLUSION: These data support the validity of
      the short six-question AIS-6 as an asthma-specific quality of life tool.

PMID- 17033906
TI  - Health status and quality of life after acute exacerbations of chronic
      obstructive pulmonary disease.

PMID- 17033907
TI  - The development of a new measure of quality of life in the management of gastro
      oesophageal reflux disease: the Reflux questionnaire.
AB  - INTRODUCTION: This paper reports on the development of a new measure of health
      related quality of life for use among patients with gastro-oesophageal reflux
      disease (GORD), funded as part of the REFLUX trial. This is a large UK multi
      centre trial that aims to compare the clinical and cost effectiveness of minimal
      access surgery with best medical treatment for patients with GORD within the NHS.
      METHOD: Potential items were identified via a series of interviews and focus
      groups carried out with patients who were receiving/had received medical or
      surgical treatment for GORD. The final measure consisted of 31 items covering 7
      categories (Heartburn; Acid reflux; Wind; Eating and swallowing; Bowel movements;
      Sleep; Work, physical and social activities). The measure produced two outputs: a
      quality of life score (RQLS) and five Reflux symptom scores. Reliability
      (internal consistency), criterion validity with the SF-36 and, sensitivity to
      change in terms of relationship with reported change in prescribed medication
      were assessed amongst a sample of 794 patients recruited into the trial. RESULTS:
      The measure was shown to be internally consistent, to show criterion validity
      with the SF-36 and sensitive to changes in patients use of prescribed medication
      at baseline and 3 month follow-up. DISCUSSION: The Reflux questionnaire is a new
      self-administered questionnaire for use amongst patients with GORD. Initial
      findings suggest that the new measure is valid, reliable, acceptable to
      respondents and simple to administer in both a clinical and research context.

PMID- 17033908
TI  - Responsiveness of the EuroQol (EQ-5D) and the Nottingham Health Profile (NHP) in
      elderly patients with femoral neck fractures.
AB  - INTRODUCTION: The objective of this study was to evaluate the internal and
      external responsiveness of the EuroQol (EQ-5D) and the Nottingham Health Profile
      (NHP) and to evaluate the overlap of change scores from the two instruments.
      METHODS: Sixty patients with femoral neck fractures treated with internal
      fixation at a university hospital participated. Internal responsiveness was
      assessed using a paired t-test and the standardised response mean (SRM) for
      patients with displaced fractures hypothesised to deteriorate between baseline
      and the 6-month follow-up. In the analyses of external responsiveness, receiver
      operator characteristics (ROC) and logistic regression were employed to assess
      the correspondence between the chosen external criterion (EC) defining fracture
      displacement, i.e. displaced vs. undisplaced fractures, and the change scores
      from the EQ-5D and the NHP. The overlap in change scores for the overall scores
      and comparable subdimensions of the two instruments was evaluated by
      correlational analyses. RESULTS: The SRM were large and the change in HRQoL over
      time was statistically significant for both instruments in patients with
      displaced fractures. A correspondence was found between the EC and change scores
      for both questionnaires. The correlation coefficients between the change scores
      for the overall scores and comparable subdimensions of the two instruments ranged
      from relatively small to moderate. CONCLUSIONS: The results yielded support for
      the internal and external responsiveness of the EQ-5D and the NHP and indicated
      an advantage for the EQ-5D. The empirical overlap between change scores from the
      two instruments was limited.

PMID- 17033909
TI  - Randomized trial results of quality of life comparing whole abdominal irradiation
      and combination chemotherapy in advanced endometrial carcinoma: A gynecologic
      oncology group study.
AB  - OBJECTIVE: To prospectively compare quality of life (QOL) outcomes in patients
      with advanced endometrial cancer treated with whole abdominal irradiation (WAI)
      or doxorubicin-cisplatin (AP) chemotherapy. METHODS: Using the Fatigue Scale
      (FS), Assessment of Peripheral Neuropathy (APN), Functional Alterations due to
      Changes in Elimination (FACE), and Functional Assessment of Cancer Therapy
      General (FACT-G), QOL was measured at: pre-treatment, end of treatment (EOT), and
      3 and 6 months post-treatment. RESULTS: 317 of 396 eligible patients provided a
      baseline QOL assessment. The AP arm produced a statistically significant survival
      benefit along with greater toxicities, including peripheral neuropathy persisting
      up to 6 months. WAI patients reported worse FS (p < 0.001) and FACE (p < 0.001)
      scores at EOT and poorer FACE scores 3 months post-treatment (p = 0.004) compared
      to AP patients. APN scores were significantly worse among AP patients at EOT, and
      3 and 6 months post-treatment (p < 0.001 for all). There is no indication that
      FACT-G scores differed between the two arms at any assessment point. CONCLUSIONS:
      The trade-off for increased survival with AP is its potential for clinically
      significant peripheral neuropathy. This should be discussed with patients,
      particularly those who work with their hands or on their feet, in weighing
      therapeutic choices. Further research is needed to manage side effects having an
      enduring impact on QOL.

PMID- 17033910
TI  - Quality of life in HIV subtype C infection among asymptomatic subjects and its
      association with CD4 counts and viral loads--a study from South India.
AB  - OBJECTIVE: To study the association between quality of life (QOL) domains and
      biological markers of disease progression of HIV infection, i.e. viral load (VL)
      and CD4 counts among asymptomatic subjects with HIV subtype C infection in South
      India. DESIGN: Quality of life was measured using the locally validated version
      of the WHOQOL HIV-BREF. The subjects were neurologically asymptomatic, non
      psychiatrically ill HIV infected men and women participating in a cohort study.
      RESULTS: The results indicated mixed findings, with some QOL dimensions being
      associated with high VLs and low CD4 counts while several others did not show any
      associations. Significant associations were seen between low CD4 counts and the
      psychological and social relationships domain, with lower mean scores in these
      domains being reported by subjects having CD4 counts <200/mm. However, there were
      no significant differences between the CD4 subgroups for the domains related to
      physical health, level of independence, environment, and spirituality domains.
      Significant lower mean QOL scores were found in the highest VL subgroup compared
      to other groups for the following WHOQOL HIV-BREF domains: physical,
      psychological, level of independence, and environmental. CONCLUSIONS: In this
      sample of HAART naive asymptomatic HIV infected subjects, some QOL dimensions
      were associated with the biological markers of disease progression i.e. VL and
      CD4 counts, while several were not. The associations were significant only in the
      high VL and low CD4 groups.

PMID- 17033911
TI  - Girls growing through adolescence have a higher risk of poor health.
AB  - INTRODUCTION: Self rated health, in adult population, is strongly associated with
      mortality and life expectancy. In younger people this association is less
      evident, but it may anticipate a similar risk in adult life. Our research, based
      on the HBSC (Health Behaviour in School-Aged Children) International
      collaboration, contributes to deepen the knowledge in this field by monitoring
      adolescents' health through a multi-national survey involving 29 European
      countries, plus North America (Canada and USA) and Israel. METHODS: Following an
      established methodology, the HBSC survey has elaborated a questionnaire on health
      and health behaviour, filled in by a representative national sample of 11-, 13-
      and 15-year-old boys and girls. The sample is constituted of more than 160,000
      subjects interviewed during the 2001/2002 survey. Reported symptoms and self
      rated health have been analysed by sex and age and through the different
      countries. RESULTS: Girls resulted to have a poorer perception of their health,
      with respect to males, at all ages and in all countries (Overall OR = 1.70, 95%
      CI: 1.66-1.76). Age increases this risk both for males and females, with an
      average increase of 32% (95% CI: 29-34%) per year in the age-range 11-15. The
      situation is similar for reported symptoms, with an overall OR of 1.81 (95% CI:
      1.77-1.85) for females of reporting three or more symptoms at least once a week;
      also this risk increases of 26% (95% CI: 24-27%) per year during the pre
      adolescence phase. In both cases it could be shown a significant interaction
      effect between age and gender: OR = 1.19 (CI: 1.15-1.23) for perceived health and
      OR = 1.26 (CI: 1.23-1.29) for reported symptoms in females with respect to males.
      CONCLUSIONS: Even if adolescence is described as the healthiest period of life, a
      consistent minority of young people perceive and report a poor health and a high
      number of symptoms. Females are constantly in a worse position than males and
      older age groups are worse than younger ones.

PMID- 17033912
TI  - Health-related quality of life and mental health problems after a disaster: are
      chronically ill survivors more vulnerable to health problems?
AB  - Studies have shown that the chronically ill are at higher risk for reduced health
      related quality of life (HRQL) and for mental health problems. A combination with
      traumatic events might increase this risk. This longitudinal study among 1216
      survivors of a disaster examines whether chronically ill survivors had a
      different course of HRQL and mental health problems compared to survivors without
      chronic diseases. HRQL and mental health problems were measured 3 weeks, 18
      months and 4 years post-disaster. Data on pre-disaster chronic diseases was
      obtained from the electronic medical records of general practitioners. Random
      coefficient analyses showed significant interaction effects for social
      functioning, bodily pain and emotional role limitations at T2 only. Chronically
      ill survivors did not consistently have a different course of general health,
      physical role limitations, and mental health problems. In conclusion, chronic
      diseases were not an important risk factor for impaired HRQL and mental health
      problems among survivors.

PMID- 17033913
TI  - Quality of life and continence in patients with spina bifida.
AB  - PURPOSE: Spina bifida (SB) is the most common congenital cause of incontinence in
      childhood. This study attempts to determine the relationships between
      urinary/faecal incontinence, methods of management, and Health Related Quality of
      Life (HRQoL) in people with SB. PATIENTS AND METHOD: A total of 460 patients (300
      adults and 160 adolescents) from six centres in France have taken part in this
      cross-sectional study. Clinical outcome measures included walking ability,
      urinary/faecal continence, and medical management. HRQoL was assessed using the
      SF36 in adults and the VSP in adolescents and their parents. Univariate and
      multivariate analysis was used to determine the relationships between clinical
      parameters and HRQoL. RESULTS: HRQoL were significantly lower than in the general
      population. Adult women had significantly lower scores than men, and adolescent
      females had significantly lower scores for psychological well being. We did not
      found strong relationship between incontinence and HRQoL in this population.
      Moreover patients surgically managed for urinary/fecal incontinence did not show
      significantly higher scores of HRQoL. CONCLUSION: Using generic HRQoL measures,
      urinary/faecal incontinence and their medical management may not play a
      determinant role in HRQoL of persons with SB. However many other factors affect
      HRQoL in these patients. A longitudinal study design is recommended to assess
      whether incontinence management is associated with improved HRQoL.

PMID- 17033914
TI  - [Abstracts of the 50th Austrian Ear Nose and Throat Congress, September 2006,
      Klagenfurt].

PMID- 17033915
TI  - Psychopathological characteristics and treatment response of first episode
      compared with multiple episode schizophrenic disorders.
AB  - OBJECTIVE: The aim was to investigate the hypothesis that patients with first
      episode schizophrenic disorders have a more favorable treatment response than
      those with multiple episodes. METHOD: A total of 400 inpatients from an ongoing
      multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic
      disorders (F2) were assessed at admission to and discharge from hospital using
      the Positive and Negative Syndrome Scale (PANSS). RESULTS: At admission, first
      episode patients (n = 121) showed higher levels of positive symptoms (PANSS
      positive subscore) and lower ones of negative symptoms (PANSS negative subscore)
      than multiple episode patients (n = 279), whereas the global disease severity
      (PANSS total score) was comparable. Analyses of covariance revealed that
      treatment response (adjusted symptom levels at discharge) was more favorable in
      first-episode patients, with respect to both positive and negative symptoms.
      CONCLUSION: The results are compatible with the hypothesis that treatment
      response becomes less favorable during the course of schizophrenic illness. This
      finding might be associated with progressive neurobiological alterations.

PMID- 17033916
TI  - Case report: Cerebral air embolization in the electrophysiology laboratory during
      transseptal catheterization: curative treatment of acute left hemiparesis with
      prompt hyperbaric oxygen therapy.
AB  - We present a case of a 44 year-old man with medically refractory symptomatic
      paroxysmal atrial fibrillation in whom the initial attempt at left atrial
      catheter ablation was complicated by coronary and cerebral arterial air
      embolization during transseptal catheter exchange. The manifestations,
      management, and long term outcomes are detailed. Following the case report is a
      review of published reports and contemporary management strategies for treatment
      of acute air embolization. Dramatic clinical consequences can be aborted by
      prompt intervention including volume loading, oxygenation, lidocaine, and
      hyperbaric oxygen therapy.

PMID- 17033917
TI  - Success rate of catheter ablation in atrial flutter: comparison of a 4- or 5-mm
      tip electrode catheter with an 8-mm tip electrode catheter.
AB  - BACKGROUND: Radio frequency (RF) energy is capable of interrupting the reentrant
      circuit of atrial flutter and curing the arrhythmia. The development of 8-mm tip
      catheter provides more tissue damage and has offered the promise of improved
      success. The purpose of our study was to determine if the acute and long-term
      success with the 8-mm tips were superior to the 4- or 5-mm tips. MATERIALS AND
      METHODS: The outcomes of the first 20 patients in whom an 8-mm tip catheter was
      used were compared with the previous 20 patients in whom a 4-or 5-mm tip catheter
      was used. Procedural (acute) ablation success was defined by creation of bi
      directional isthmus block. Long-term success was defined as the prevention of
      clinically evident atrial flutter (AFl) as determined by the absence of symptoms
      or maintenance of sinus rhythm on electrocardiogram, six months to one year after
      the procedure. RESULTS: Compared to the 4- or 5-mm tip, the 8-mm catheter tip was
      associated with a reduced ablation duration {22.3 +/- 16 versus 11.5 +/- 5 min (p
      = 0.0078)}, a lower mean number of ablations {13.5 +/- 9.9 versus 6.8 +/- 2.9 (p
      = 0.0065)} and a reduced procedure time {1.8 +/- 0.7 versus 1.1 +/- 0.5 h (p =
      0.0032)}. Acute success was 95% in the 4- or 5-mm group versus 80% in the 8-mm
      group (p = NS), but long-term success was higher in the 8-mm group than the 4- or
      5-mm group (87.5 versus 63.2%, p = 0.0436). CONCLUSIONS: Eight-millimeter tip
      catheters for AFl shorten procedure time, reduce the duration and number of
      ablations and accomplish bi-directional block when compared with smaller tipped
      catheters. The long-term success rate is better with the 8-mm tips and should be
      the preferred catheter for RF ablation of AFl.

PMID- 17033918
TI  - Breast cancer incidence trends in deprived and affluent Scottish women.
AB  - OBJECTIVE: Breast cancer is commoner in the affluent and breast cancer rates in
      many countries are rising; it remains unclear whether this incidence rise is
      consistent across the different socio-economic groups. The rising incidence of
      breast cancer may be related to changes in population risk factor profiles. This
      study aimed to determine breast cancer incidence trends in women of different
      socio-economic categories and whether these trends were related to breast cancer
      risk factor trends. DESIGN: Data on breast cancer incidence rates by deprivation
      quintile in Scotland 1991-2000 were analysed using linear regression. Data on
      first births at late maternal age, BMI trends (based on the Scottish Health
      Surveys) and breast screening uptake trends in the different categories were also
      analysed and their relation to breast cancer incidence trends explored.
      POPULATION AND SETTING: Breast cancer incidence data was based on all women in
      Scotland. BMI data was based on representative cross-sectional survey data from
      the Scottish Health Surveys-women in the 1995, 1998 and 2003 surveys were 16-64,
      16-74 and aged 16 and over, respectively. First birth data was based on all women
      aged 35-39 in Scotland. Breast screening uptake data was studied in women of
      screening age, that is, aged 50-64. RESULTS: Breast cancer incidence rates in
      Scottish women are rising in parallel across all socio-economic categories and
      the incidence gap between deprived and affluent still remains. Since the late
      1980s, numbers of first birth in Scottish women aged 35-39 have risen
      dramatically, especially in the affluent, but numbers were stable before this.
      The prevalence of obesity and mean BMI has increased over time in all socio
      economic classes but BMI continues to be higher in the deprived. Uptake of
      screening invitations has increased in all socio-economic groups. CONCLUSIONS:
      Breast cancer is rising in women of all socio-economic status in Scotland and the
      deprived-affluent gap remains. Trends in late age at first pregnancy, prevalence
      of obesity and screening uptake do not fully explain the observed trends.

PMID- 17033919
TI  - Male breast cancer: a review of clinical management.
AB  - AIMS: Male breast cancer incidence is 1% of all breast cancers and is increasing.
      We aim to present an overview of male breast cancer with particular emphasis on
      clinical management. METHODS: Studies were identified by an online search of
      literature in the MEDLINE database till June 2006 followed by an extensive review
      of bibliographies. RESULTS: Increased risk factors include genetic predisposition
      as in BRCA2 families; testicular dysfunction due to chromosomal abnormality such
      as Klinefelter's syndrome or environmental factors such as chronic heat exposure
      and radiation. Clinical assessment with biopsy is the hallmark of diagnosis.
      Earlier presentations are becoming commoner but there are wide geographical
      differences. Surgical treatment involves simple or modified radical mastectomy
      along with surgical assessment of the axilla, either via sentinel node biopsy in
      clinically node-negative disease or axillary sampling/clearance in node-positive
      disease. Reconstructions for restoring body image have been recently reported.
      Indications for adjuvant therapies are similar to that in women. For metastatic
      disease, tamoxifen is still the mainstay for oestrogen receptor positive disease.
      For oestrogen receptor negative disease, doxorubicin based chemotherapy regimens
      are used. In addition, the oft neglected psychological aspects of men having a
      "cancer of women" are increasingly being recognised. CONCLUSIONS: There is, thus,
      need for further increasing awareness among men to reduce stigma associated with
      presentation of symptoms related to breast. This should be in addition to
      stressing to clinicians the ways of earlier detection and tailor-made "gender
      oriented" treatment of breast cancer in men.

PMID- 17033920
TI  - Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a
      triage test in breast cancer staging.
AB  - INTRODUCTION: Axillary node fine needle aspiration cytology (FNAC) has the
      potential to triage women with operable breast cancer to initial nodal surgical
      procedure. Because of variability in the reported accuracy of this test its role
      and clinical utility in pre-operative staging remains controversial. METHODS: We
      retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all
      consecutive clinically T1-2 N0-1 breast cancers that had undergone this test (491
      biopsies). We included subjects with clinically or sonographically indeterminate
      or suspicious nodes. Pathological node status was used as the reference standard
      (based on axillary dissection or sentinel node biopsy). RESULTS: Sensitivity of
      node FNAC was 72.6% (67.3-77.9) and specificity was 95.7% (92.5-98.8) for all
      cases, sensitivity was lower at 64.6% (59.3-70.0) if inadequate cytology was
      included as a negative result. FNAC sensitivity was highest in women with
      clinically suspicious nodes [92.5% (88.2-96.7)] and lowest in women with
      sonographically abnormal and clinically negative nodes [50.0% (41.3-58.7)].
      Specificity was high in both groups, 81.2% (54.5-96.0) and 97.2% (94.6-99.9),
      respectively. The false-negative rate was 15.3% (12.1-18.5), the false-positive
      rate was 1.4% (0.4-2.5), and the inadequacy rate was 10.8% (8.0-13.5). The
      likelihood of node FNAC being positive was significantly associated with tumour
      grade and stage, and the number of nodes involved with metastases. DISCUSSION:
      Our data show that axillary FNAC has moderate sensitivity (which varies according
      to selection criteria for the test) and consistently high specificity, is
      associated with low inadequacy and very few false positives. We estimate that its
      use would have improved triage to initial nodal procedure in about one quarter of
      our cases. If one accepts the premise that initial surgical staging of the axilla
      should be based on all information available through pre-operative diagnosis,
      then axillary FNAC should be adopted routinely into clinical practice.

PMID- 17033921
TI  - The effects of radiotherapy for the treatment of contralateral breast cancer.
AB  - Radiotherapy following breast-conserving surgery for the treatment of first
      primary breast cancer is the standard of care and is widely used despite its
      small survival benefit. The effects of radiotherapy in metachronous contralateral
      breast cancer are unknown. We examined the use of radiotherapy and its effect on
      cause-specific and all-cause mortality among women with metachronous
      contralateral breast cancer treated with breast-conserving surgery in community
      settings. Using data from the 1985-2000 Surveillance, Epidemiology, and End
      Results program, we identified women with stage 0-III metachronous contralateral
      breast cancer that occurred at least six months after stage 0-III first primary
      breast cancer. Cause-specific and all-cause mortality of women age 40-69 who did
      and who did not receive radiotherapy following breast-conserving surgery for
      metachronous contralateral breast cancer were compared in proportional hazard
      models using propensity scores to balance covariates by radiotherapy use. We
      adjusted for misclassification of radiotherapy use. Based on misclassification
      corrected analyses, 43.2 percent of 1,083 women with metachronous contralateral
      breast cancer did not receive radiotherapy after BCS. After adjustment for
      propensity scores and radiotherapy misclassification, women who did not receive
      radiotherapy had 2.2 times greater risk of cause-specific and 1.7 times greater
      risk of all-cause mortality. In community settings, a high percentage of women
      with stage 0-III metachronous contralateral breast cancer did not receive
      radiotherapy following breast-conserving surgery. Unlike the small survival
      benefit of radiotherapy after first primary breast cancer, omission of
      radiotherapy after metachronous contralateral breast cancer significantly
      increased the risk of cause-specific and all-cause mortality.

PMID- 17033922
TI  - Characterization of molecular and structural determinants of selective estrogen
      receptor downregulators.
AB  - Antiestrogens used for breast cancer therapy can be categorized into two classes
      that differ in their effect on estrogen receptor (ER) alpha stability. The
      selective estrogen receptor modulators (SERMs) stabilize ER alpha and the
      selective estrogen receptor downregulators (SERDs) cause a decrease in cellular
      ER alpha levels. A clinically relevant antiestrogen, GW7604, appears to work
      through a SERD-like mechanism, despite sharing the same molecular scaffold as 4
      hydroxytamoxifen, a SERM. In order to investigate potential structural features
      of GW7604 responsible for SERD activity, GW7604 and two analogs were synthesized
      using a new, improved synthetic route and tested for their effects on ER alpha
      function and cell proliferation. The two analogs, which have an acrylamide or a
      methyl vinyl ketone replacing the acrylic acid group of GW7604, display lower
      binding affinity for ER alpha than GW7604, but show similar antagonism of
      estradiol-induced activation of ER alpha-mediated transcription as GW7604 and
      inhibit estradiol-induced proliferation of the MCF-7 cell line with a similar
      potency as GW7604. Unlike GW7604, neither analog has a significant effect on
      cellular ER alpha levels, suggesting that the carboxylate is a key determinant in
      GW7604 action and, for the first time, showing that this group is responsible for
      inducing ER alpha degradation in breast cancer cells.

PMID- 17033923
TI  - Magnetic resonance imaging of breast lesions--a pathologic correlation.
AB  - Magnetic resonance imaging of the breast is useful in assessing breast lesions.
      An understanding of the pathologic characteristics of the tumors may help to
      understand these magnetic resonance imaging observations.Large lesional size (>10
      mm), ill-defined margin, and irregular outlines are associated with malignancy.
      These correlate with the pathological features of breast tumor, characterized by
      rapid growth rate, large size, and infiltrative growth pattern, invasion into
      stroma resulting in desmoplasia, and hence irregular outline and margin. The
      detection and estimation of tumor extent of invasive lobular carcinoma is
      problematic, even with magnetic resonance imaging, which is considered the most
      sensitivity. This inaccuracy likely derives from the characteristic linear,
      single cells infiltration growth pattern of the tumor, which is also often
      underestimated by clinical examination. Estimation of tumor extent after
      neoadjuvant chemotherapy is also essential but problematic by imaging, as the
      shrunken tumor becomes fibrotic, with stromal hyalinization, diminished
      microvasculature and tumor break up causing size underestimation. Non-enhancement
      of breast tumors occurs in about 8% of cases correlates with diffuse growth
      pattern, particularly of infiltrative lobular carcinoma. The observation of
      disproportionately high non-enhancing ductal carcinoma in situ remains an enigma.
      Finally, early rim enhancement correlates with small cancer nests, low ratio of
      peripheral to central fibrosis and high ratio of peripheral to central
      microvessel density. These may be related to increased vascular endothelial
      growth factor mediated increased microvessel density as well as increased
      permeability, which manifest as increased rapid contrast uptake and dissipation.

PMID- 17033924
TI  - Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few
      associations with breast cancer susceptibility and progression.
AB  - The importance of matrix metalloproteinases and their inhibitors in tumor
      progression is well documented. We wanted to investigate if single nucleotide
      polymorphisms (SNPs) in the promoter regions of these genes are associated with
      susceptibility to or progression of breast cancer. In this, so far largest case
      control study, we genotyped eight SNPs in the MMP1, MMP2, MMP3, MMP9, MMP13, RECK
      and TIMP3 genes in a well-characterized breast cancer series of 959 cases and 952
      controls from Sweden. Even though we did not correct for multiple comparisons,
      only a few associations were noted. We observed a moderately increased risk for
      the TT homozygotes of the MMP9-1562 C/T SNP (OR 1.88, 95% CI 0.97-3.63) and for
      the C allele carriers of the TIMP3-1296 T/C SNP (OR 1.25, 95% CI 1.05-1.50). In
      the survival analysis, only the TC heterozygotes of the RECK-420 T/C SNP showed a
      better survival compared to the TT homozygotes (P = 0.02 in all cases and P =
      0.03 in lymph node negative cases). None of the other SNPs conferred an increased
      breast cancer risk, nor did they correlate with survival. A combination of the 
      585 TT homozygosity in the RECK gene and the -1296 TT homozygosity in the TIMP3
      gene correlated with estrogen and progesterone receptor status (OR 1.81, 95% CI
      1.03-3.21 and OR 2.10, 95% CI 1.18-3.86, respectively), and a combination of the 
      1306 TT homozygosity in the MMP2 gene and the -1562 CC homozygosity in the MMP9
      gene with progesterone receptor status (OR 2.34, 95% CI 1.08-5.08). Although our
      study suggests some correlations between the studied SNPs and the progression of
      breast cancer, the rarity of the risk genotypes limits their usefulness in the
      clinic.

PMID- 17033925
TI  - Reproductive factors and breast cancer risk among older women.
AB  - Reproductive factors have been shown to affect pre- and postmenopausal breast
      cancer risk differently, but whether there are additional age-specific
      differences among menopausal women as they age has not been clarified. We
      analyzed data from a large population-based case-control study that included
      1,508 breast cancer cases and 1,556 controls, aged 20-98 years, who completed an
      in-home interviewer-administered questionnaire. The following subgroups were
      created to examine if the associations between reproductive factors and breast
      cancer risk varied by age- and menopausal-status: premenopausal (n=968),
      postmenopausal <65 years (n=1,045), postmenopausal >or=65 years (n=958). Among
      postmenopausal women >or=65 years, ever having breastfed decreased risk (odds
      ratio (OR)=0.67, 95% confidence interval (CI)=0.48, 0.92), and a strong dose
      response relationship was observed for longer durations of breastfeeding (P
      trend=0.02), with the most pronounced protective effect observed for >or=14
      months of breastfeeding (OR=0.40, 95% CI=0.21,0.76). Late age at first birth
      (AFB) and older age at last birth (ALB) were associated with non-statistically
      significant increases in breast cancer risk in this older group, while late age
      at menarche and surgical menopause decreased risk. ORs for multiparity were close
      to the null. Among premenopausal women and postmenopausal women <65 years,
      multiparity significantly decreased risk, and older AFB nonsignificantly
      increased risk. Our findings suggest that the well-known protective effect of
      multiparity attenuates with older age. Moreover, breastfeeding, one of the few
      potentially modifiable risk factors for breast cancer, was an important factor in
      decreasing risk among older parous postmenopausal women.

PMID- 17033926
TI  - Thirty-year follow-up of chemo/hormonal therapy in node-positive breast cancer.
AB  - Results of a thirty-year follow-up of a clinical trial of chemo-hormonal therapy
      are reported. Eligible patients had recently diagnosed operable breast cancer,
      positive lymph nodes, no previous history of cancer, age less than 76 years, and
      no evidence of metastatic disease. A total of 311 patients were stratified by
      estrogen receptor (ER) status and number of axillary nodes involved with tumor.
      After stratification, patients were randomly assigned to one of three treatment
      regimens: cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for 1 year; CMF
      chemotherapy combined with anti-estrogen therapy (tamoxifen) for 1 year; or CMF
      plus tamoxifen with BCG during the second year. The endpoint of the trial was a
      first recurrence. Factors measured at diagnosis and used in the analyses were
      age, body mass index, ER status, menopausal status, number of positive nodes,
      tumor diameter, Charlson comorbidity index, socioeconomic status, and race.
      Causes of death and incidence of other cancer primaries were obtained from death
      certificates and medical records. Patients treated with tamoxifen had a
      marginally longer disease-free survival (hazard ratio (HR)=0.83, 95% CI identical
      with [0.66, 1.04]) and statistically significant longer overall survival
      (HR=0.77, 95% CI identical with [0.63, 0.96]) that decreased with time. Incidence
      of other primary cancers and causes of death were similar for the two treatment
      groups. The addition of 1 year of tamoxifen to CMF therapy provides an early
      disease-free and overall survival advantage; however long-term effects are
      negligible. Similarly, the survival advantage of patients diagnosed with ER+
      tumors persists for the first two decades after diagnosis.

PMID- 17033927
TI  - Cost-effectiveness of exemestane versus tamoxifen as adjuvant therapy for early
      stage breast cancer after 2-3 years treatment with tamoxifen in Sweden.
AB  - Aromatase inhibitors are rapidly becoming the cornerstone of endocrine treatment
      for advanced disease and are now also used as adjuvant treatment in early-stage
      disease. The objective of this study was to assess the cost-effectiveness of
      adjuvant treatment with exemestane versus tamoxifen for early-stage breast cancer
      after 2-3 years treatment with tamoxifen in Sweden. The results are based on
      findings in the Intergroup Exemestane Study (IES). IES was a randomized
      controlled trial in which postmenopausal women who had received 2-3 years of
      tamoxifen therapy following primary treatment of early-stage breast cancer, were
      randomized to either continue on tamoxifen therapy or be switched to exemestane
      therapy. The results showed a disease-free survival hazard ratio of exemestane
      relative to tamoxifen in IES of 0.69. A Markov state-transition model was
      developed to simulate consequences after the end of the clinical trial, and to
      integrate the trial data with external data on mortality, costs and quality of
      life specific for Swedish women. The cost per QALY gained was about euro 20,000
      in the base case analysis without inclusion of consequences of coronary heart
      disease. Inclusion of these events increased the cost-effectiveness ratio to
      about euro 31,000. This means that, based on our assumption, sequential
      exemestane treatment in early breast cancer is a cost-effective option compared
      with tamoxifen alone, although more long-term data on overall survival and
      consequences of adverse events would be valuable to increase the validity of the
      analysis further.

PMID- 17033928
TI  - The impact of breast cancer awareness and socioeconomic status on willingness to
      receive breast cancer prevention drugs.
AB  - PURPOSE: To find associations between knowledge about risk factors for breast
      cancer and the socioeconomic status of healthy women, as well as their attitude
      toward taking chemopreventive drugs. PATIENTS AND METHODS: Between April and
      September 1999, 7135 healthy women completed questionnaires providing information
      about their willingness to take chemopreventive drugs. Items in the questionnaire
      included the sources of the information they had, their estimates of the
      population and personal lifetime risk, and risk factors for breast cancer.
      RESULTS: A total of 6597 questionnaires were evaluable. The responders' median
      age was 44. Fifty-five percent of the women were willing to consider receiving
      chemopreventive drugs to lower their risk for breast cancer. Participants who
      estimated the population risk as being very high were more disposed to receive
      chemoprevention (65.3%), as were women who estimated their own breast cancer risk
      as being high (74.1%). A family history of breast cancer only had a low impact on
      willingness to receive chemoprevention. Women with a family history of breast
      cancer were willing to take chemopreventive agents in 57.2% of cases. The
      multivariate analysis showed that knowing about risk factors and having a lower
      educational level were factors positively correlated with willingness to consider
      chemoprevention. CONCLUSION: These findings emphasize the role of estimations of
      the risk of breast cancer for patients considering whether to accept
      chemoprevention treatment. To date, only a few modern models of risk estimation
      have been evaluated in relation to chemoprevention. There is a need for better
      integration of professional risk estimations into clinical practice.

PMID- 17033929
TI  - Computed tomography in suspected local breast cancer recurrence.
AB  - PURPOSE: The purpose of this prospective study was to test computed tomography
      (CT) in the evaluation of local breast cancer recurrence. MATERIALS AND METHODS:
      Our study population included 103 women referred for mamma CT examination for
      reasons of suspicious findings in a conservatively treated breast. In these
      patients, both clinical and conventional imaging studies (mammography,
      ultrasonography) features of local recurrences were non specific or suspicious.
      The patients underwent breast CT before and 90 s after intra-venous contrast
      medium administration. Criterion for cancer recurrence was detection of a lesion
      with an enhancement of 20 UH or more. The final diagnosis was based on operative
      histopathological findings or follow-up for over two years. RESULTS: Local
      recurrence was confirmed on histology in 52 patients. CT identified 47 breast
      recurrent cancers. False-positive contrast enhancement was seen in five patients.
      CT showed 90% sensitivity, 90% specificity and 90% accuracy. CONCLUSION: Although
      mamma CT examination proved to have a high diagnostic efficacy in evaluating
      breast cancer recurrence, routine computed tomography is unnecessary for most
      patients.

PMID- 17033930
TI  - Teaching the imitation and spontaneous use of descriptive gestures in young
      children with autism using a naturalistic behavioral intervention.
AB  - Children with autism exhibit deficits in the imitation and spontaneous use of
      descriptive gestures. Reciprocal Imitation Training (RIT), a naturalistic
      imitation intervention, has ben shown to increase object imitation skills in
      young children with autism. A single-subject, multiple-baseline design across
      five young children with autism was used to determine whether RIT could be
      adapted to target the imitation of descriptive gestures. All participants
      increased their imitation of gestures in the treatment setting and on a
      structured imitation assessment. Gains generalized to a novel therapist, setting,
      and materials and maintained at a 1-month follow-up. Three participants also
      increased their spontaneous use of descriptive gestures. These results provide
      support for the effectiveness of a naturalistic intervention for teaching gesture
      imitation.

PMID- 17033931
TI  - Microbiological characteristics of a sandy loam soil exposed to tebuconazole and
      lambda-cyhalothrin under laboratory conditions.
AB  - Changes in microbiological properties of a sandy loam soil in response to the
      addition of different concentrations of fungicide tebuconazole and pyrethroid
      insecticide lambda-cyhalothrin were assessed under laboratory conditions. To
      ascertain these changes, the potentially active soil microbial biomass,
      concentrations of ammonium and nitrate ions, numbers of total culturable
      bacteria, fungi, nitrogen-fixing bacteria, nitrifying and denitrifying bacteria
      were determined. Substrate-induced respiration (SIR) increased with time in both
      control (ranged from 13.7 to 23.7 mg/O(2)/kg(-1)/dry soil/h(-1)) and pesticide
      treated soil portions. For both pesticides, SIR values ranged from 12-13 to 23-25
      mg/O(2)/kg(-1)/dry soil/h(-1) on days 1 and 28, respectively. Also,
      concentrations of nitrate and ammonium ions, numbers of total culturable
      bacteria, denitrifying bacteria, nitrogen-fixing bacteria (for the insecticide)
      and fungi (for the insecticide) were either unaffected or even stimulated by the
      pesticide treatments. The adverse impacts of the pesticides were observed for
      nitrate concentrations (on days 1 or 7), numbers of nitrifying bacteria (on day
      1), denitrifying bacteria (for the insecticide on days 1 and 14), nitrogen-fixing
      bacteria (for tebuconazole on day 1) as well as numbers of fungi in tebuconazole
      treated soil (on days 1 and 14).

PMID- 17033932
TI  - Do access experiences affect parents' decisions to enroll their children in
      Medicaid and SCHIP? Findings from focus groups with parents.
AB  - OBJECTIVE: The Covering Kids and Families (CKF) program seeks to expand health
      insurance coverage for children by supporting community-based outreach and
      enrollment. For the evaluation of CKF, researchers conducted focus groups to
      explore parents' experiences accessing health care for their children, and to
      assess whether these experiences affected decisions to enroll their children in
      Medicaid or the State Children's Health Insurance Program (SCHIP). METHODS: In
      May and June 2003, 13 focus groups were conducted in 5 cities--Everett, MA;
      Denver, CO; Los Angeles, CA; Mena, AR; and San Antonio, TX. In each community,
      groups were conducted with parents of children insured under Medicaid or SCHIP
      and parents of uninsured children. Three groups were conducted with Spanish
      speaking parents in two communities--Denver and Los Angeles. RESULTS: Access to
      primary care was considered good by most parents with children in Medicaid and
      SCHIP. Among parents of uninsured children, there was more variation in
      perceptions of access to care. For parents of both uninsured and insured
      children, access to dentists and specialists was more problematic. Spanish
      speaking families reported numerous barriers to care due to language differences
      and perceived discrimination. All focus group participants said that they placed
      great value on health insurance. CONCLUSION: Even when parents encountered
      problems accessing care, very few indicated that this discouraged them from
      enrolling their children into Medicaid or SCHIP, or from renewing their
      children's public coverage.

PMID- 17033933
TI  - Doing the difficult and dangerous: the community program practice scale.
AB  - The CPPS uses staff respondents to portray practices and program climate of
      nonresidential mental health programs. We report psychometric analyses of 1,533
      respondents in 165 programs. Confirmatory factor and partial credit analyses
      identified eight practice and five climate subscales, all of which show adequate
      psychometric properties. Program types are distinguished better by practices (R
      (2) values .37 to .52) than by climate (R (2) values .09 to .23), as expected.
      Multiple discriminant analysis and K-means cluster analysis illustrate how well
      the CPPS distinguishes program differences. The CPPS offers a promising,
      economical approach to measuring program practices in clinical trials comparing
      service programs.

PMID- 17033934
TI  - Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with
      impaired spatial learning and reduced control of exploratory behavior.
AB  - Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation
      associated with skeletal abnormalities. It is caused by mutations of the Rsk2
      gene, which encodes a growth factor regulated kinase. Gene deletion studies in
      mice have shown an essential role for the Rsk2 gene in osteoblast differentiation
      and function, establishing a causal link between Rsk2 deficiency and skeletal
      abnormalities of CLS. Although analyses in mice have revealed prominent
      expression of Rsk2 in brain structures that are essential for learning and
      memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive
      function is still lacking. Here, we have examined Rsk2-deficient mice in two
      extensive batteries of behavioral tests, which were conducted independently in
      two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known
      reduction of bone mass, all parameters of motor function were normal, confirming
      the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient
      mice showed a mild impairment of spatial working memory, delayed acquisition of a
      spatial reference memory task and long-term spatial memory deficits. In contrast,
      associative and recognition memory, as well as the habituation of exploratory
      activity were normal. Our studies also revealed mild signs of disinhibition in
      exploratory activity, as well as a difficulty to adapt to new test environments,
      which likely contributed to the learning impairments displayed by Rsk2-deficient
      mice. The observed behavioral changes are in line with observations made in other
      mouse models of human mental retardation and support a role of Rsk2 in cognitive
      functions.

PMID- 17033935
TI  - Testing descriptive hypotheses regarding sex differences in the development of
      conduct problems and delinquency.
AB  - Accurate descriptions of sex differences in the development of childhood conduct
      problems and adolescent delinquency will inform theories of their causes in
      fundamentally important ways. Using data on 4,572 offspring of a national sample
      of women, we tested descriptive hypotheses regarding sex differences. As
      predicted, the magnitude of sex differences varied with age, suggesting that
      multiple processes differentially influence levels of these behaviors in females
      and males across development. During childhood, boys scored lower on measures of
      cognitive ability and exhibited lower sociability and compliance and greater
      hyperactivity, oppositional behavior, and conduct problems. Most of these
      variables were associated with childhood conduct problems and adolescent
      delinquency equally in females and males, but maternal delinquency and early
      childhood sociability were correlated more strongly with childhood conduct
      problems in males and childhood compliance predicted adolescent delinquency more
      strongly in females. Both sexes exhibited both childhood-onset and adolescent
      onset trajectories of delinquency. Although more males followed a childhood-onset
      trajectory, there were few sex differences in the early childhood risk correlates
      of either delinquency trajectory.

PMID- 17033936
TI  - Power doppler ultrasound assessment of the relationship between age and ovarian
      perifollicular blood flow in women undergoing in vitro fertilization treatment.
AB  - PURPOSE: To examine the relationship between age and ovarian perifollicular blood
      flow (PFBF) in women undergoing IVF. METHODS: Serial transvaginal power Doppler
      ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively
      throughout the follicular phase of ovarian stimulation in women undergoing IVF.
      The ultrasound assessment days were categorized according to day of hCG trigger.
      RESULTS: A total of 1050 ovarian follicles from 34 women undergoing one IVF
      treatment cycle were used for data analysis. The median age of the women was 38.5
      years, ranging from 28 years to 44 years. There was a significant negative
      correlation between age and ovarian PFBF on the day of hCG trigger or trigger day
      minus 1, but not beforehand during the follicular phase. CONCLUSIONS: There was a
      significant negative correlation between age and ovarian PFBF in women undergoing
      IVF which was only observed very late in the follicular phase of ovarian
      stimulation.

PMID- 17033937
TI  - Genotyping of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
      presenting as male infertility: case report and literature review.
AB  - We describe here two infertile male patients who were referred to our hospital
      with azoospermia at the ages of 33 and 30 years, respectively. Hormonal
      examinations led to a diagnosis of congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency in both patients. Genotyping revealed that the patients
      had a homozygous I172N and a heterozygous compound I172N/IVS2-13A/C>G mutation,
      respectively. Glucocorticoid replacement therapy succeeded in improving the
      seminal status of one patient, but not the other. For the latter patient and his
      wife, a pregnancy was achieved by testicular sperm extraction (TESE) and
      intracytoplasmic sperm injection (ICSI) following genetic counseling. It is
      important to investigate genotyping and to classify patients on the basis of
      genotypic information in order to arrive at better treatment strategies for male
      infertility; especially in counseling of TESE-ICSI.

PMID- 17033938
TI  - Adaptations to oxidative stress induced by vitamin E deficiency in rat liver.
AB  - Vitamin E deficiency in rats led to a sequence of antioxidant defense adaptations
      in the liver. After three weeks, alpha-tocopherol concentration was 5% of
      control, but ascorbate and ubiquinol concentrations were 2- to 3-fold greater
      than control. During the early phase of adaptation no differences in markers of
      lipid peroxidation were observed, but the activities of both cytochrome b5
      reductase and glucose-6-phosphate dehydrogenase were significantly greater in
      deficient livers. By nine weeks, accumulation of lipid peroxidation end products
      began to occur along with declining concentrations of ascorbate, and higher NQO1
      activities. At twelve weeks, rat growth ceased, and both lipid peroxidation
      products and cytosolic calcium-independent phospholipase A2 reached maximum
      concentrations. Thus, in growing rats the changes progressed from increases in
      both ubiquinol and quinone reductases through accumulation of lipid peroxidation
      products and loss of endogenous antioxidants to finally induction of lipid
      metabolizing enzymes and cessation of rat growth.

PMID- 17033939
TI  - PRUNE and NM23-M1 expression in embryonic and adult mouse brain.
AB  - A genetic interaction between PRUNE and NM23/NDPK has been postulated in
      Drosophila melanogaster. Many have focused on Drosophila for the genetic
      combination between PRUNE "knock down" and AWD/NM23 fly mutants bearing the P97S
      mutation (K-pn, Killer of PRUNE mutation). We postulated a role for PRUNE-NM23
      interactions in vertebrate development, demonstrating a physical interaction
      between the human PRUNE and NM23-H1 proteins, and partially characterizing their
      functional significance in cancer progression. Here, we present an initial
      analysis towards the functional characterization of the PRUNE-NM23 interaction
      during mammalian embryogenesis. Our working hypothesis is that PRUNE, NM23-H1 and
      their protein-protein interaction partners have important roles in mammalian
      brain development and adult brain function. Detailed expression analyses from
      early mouse brain development to adulthood show significant co-expression of
      these two genes during embryonic stages of brain development, especially focusing
      on the cortex, hippocampus, midbrain and cerebellum. We hypothesize that their
      abnormal expression results in an altered pathway of activation, influencing
      protein complex formation and its protein partner interactions in early
      embryogenesis. In the adult brain, their function appears concentrated towards
      their enzyme activities, wherein biochemical variations can result in brain
      dysfunction.

PMID- 17033940
TI  - Telephone-delivered interventions for people living with HIV/AIDS: guest
      editorial.

PMID- 17033942
TI  - Acute scrotum in a neonate.

PMID- 17033943
TI  - Acute appendicitis: sonographic evaluation.

PMID- 17033944
TI  - How European has "Ultrasound in Medicine" become?

PMID- 17033945
TI  - Transcutaneous contrast enhanced sonography of the chest for evaluation of
      pleural based pulmonary lesions: experience in 137 patients.
AB  - PURPOSE: Transcutaneous ultrasound enables visualization of pleural based lesions
      but with a poor correlation to specific pathology. Ultrasound contrast agents in
      conjunction with contrast specific imaging techniques are increasingly accepted
      in clinical use. Up to date there are no data about the use of contrast enhanced
      sonography (CES) in a large series of pleural based pulmonary lesions. MATERIALS
      AND METHODS: From August 2004 to August 2005, 137 consecutive patients with
      pleural based pulmonary lesions on B-mode sonography were studied by CES using a
      transcapillary second-generation contrast agent (SonoVue(R)). The following CES
      parameters were retrospectively evaluated. Time to enhancement (TE) of contrast
      agent after i. v. application was determined and classified as short TE (< = 6
      sec) vs. delayed TE (> 6 sec). Extent of enhancement (EE) was evaluated during
      the arterial phase (2 - 30 sec) and the parenchymal phase (1 - 5 minutes) by
      using the normal splenic tissue as an in vivo reference, and classified in
      reduced EE (anechoic/hypoechoic) vs. marked EE (isoechoic/hyperechoic) during
      both phases. Homogeneity of enhancement (HE) was classified as homogeneous vs.
      inhomogeneous. 60 patients had histologically confirmed malignant lesions due to
      central lung cancer (n = 31), and peripheral malignant lesions (n = 29). 77
      patients had benign pleural based lesions including pneumonia (n = 32), pulmonary
      embolism (n = 20), compression atelectasis (17), and other benign pleural based
      lesions (n = 8). RESULTS: Malignant and benign lesions did not vary significantly
      regarding TE, EE, and HE. However, there were highly significant differences in
      the ratio of short vs. delayed TE and reduced vs. marked EE between the six
      disease groups. Characteristic patterns were short TE with marked EE in all
      compression atelectasis cases and in 62 % of patients with pneumonia. Delayed TE
      and reduced EE was seen in all patients with pulmonary embolism and in 62 % of
      patients with peripheral malignant lesions. Central lung cancer and benign
      nodules did not present with such specific patterns. No significant differences
      in HE were seen between subgroups. CONCLUSION: Pulmonary lesions are
      characterized by different CES-patterns of arterial supply as evidenced by TE and
      EE which depends on underlying causes, but CES does not allow to distinguish
      benign from malignant pleural based lesions in general.

PMID- 17033946
TI  - [Low-MI-sonography with the contrast-agent SonoVue in the diagnosis of infarction
      of the spleen, kidney, liver and pancreas].
AB  - PURPOSE: The diagnosis of ischemic injury by B-mode-sonography is difficult in
      many cases. Aim of the pilot-study was to evaluate whether additional examination
      with the ultrasound contrast agent SonoVue could improve the sonographic
      diagnosis of ischemic injury. MATERIALS AND METHODS: In a prospective study,
      intra-abdominal organs (n = 12) with ischemic lesions found by CT-scan were
      examined. All ischemic organs were examined by native B-mode-sonography and after
      injection of 1.2 ml SonoVue i. v. The SonoVue-examinations were performed using
      the CPS-software (Siemens, Erlangen). RESULTS: Native B-mode-sonography detected
      demarcation of ischemic lesions in only 7 of the 12 organs. In contrast, SonoVue
      enhanced sonography diagnosed ischemic lesions in all organs. In one patient with
      renal infarction, however, the ischemic lesion found by SonoVue-enhanced
      sonography was smaller compared with the CT-scan. The diagnosis "compatible with
      ischemia" as cause for the abnormalities in B-mode sonography was described in
      only 3 out of 12 organs, and none of the organs were classified as "definite
      diagnosis of ischemia". In contrast, the diagnosis "definite diagnosis of
      ischemia" was made in 10 of the 12 organs when examined with SonoVue-enhanced
      sonography. In two further patients, the lesion was classified as "compatible
      with ischemia". In these patients, the diagnosis of ischemia was verified by CT
      scan, due to the accompanying subtotal splenic infarction and a partial
      thrombosis of the coeliac trunc. CONCLUSION: It became evident that SonoVue
      enhanced sonography was more sensitive in the diagnosis of ischemic injury than
      native B-mode sonography.

PMID- 17033947
TI  - 3D ultrasound examination of the superficial lymph nodes--does it provide
      additional information?
AB  - PURPOSE: To compare the appearance of superficial lymph nodes on standard two
      dimensional (2D) ultrasound examination and on three-dimensional (3D) ultrasound
      examination. MATERIALS AND METHODS: Fifty two lymph nodes (35 cervical, 16
      axillary, 1 inguinal) in 52 patients were examined with ultrasound in 3D mode. In
      standard 2D grey-scale examination and on a C-plane of 3D mode (parallel to the
      surface of the probe), the shape of a lymph node and its hilum were assessed.
      Final histopathological diagnoses included 36 lymphomas, 11 reactive or
      inflammatory lymph nodes, 3 metastases and 2 plasmocytoma infiltrations. RESULTS:
      The appearance of hilums and lymph nodes as a whole changed on a C-plane of 3D
      mode (as compared with 2D presentation) in 28 % and 37 %, respectively. The
      differences in lymph node shape on 2D and 3D ultrasound were apparent in a
      comparable percentage of reactive lymph nodes (45 %) and lymphomatous lymph nodes
      (39 %). The differences in lymph node hilum shape on 2D and 3D ultrasound applied
      to 56 % of reactive lymph nodes and 20 % of lymphomatous lymph nodes. CONCLUSION:
      Three-dimensional imaging on a C-plane (parallel to the surface of the probe) may
      supply the examiner with different information concerning the shape of the lymph
      node and its hilum in comparison to standard 2D ultrasound. Changes in the shapes
      of hilum and lymph node occurred in reactive or inflamed lymph nodes as well as
      in lymphomas. Clinical significance of this fact demands further investigation.

PMID- 17033956
TI  - Nucleotide-resolution mapping of topoisomerase-mediated and apoptotic DNA strand
      scissions at or near an MLL translocation hotspot.
AB  - The emergence of therapy-related acute myeloid leukemia (t-AML) has been
      associated with DNA topoisomerase II (TOP2)-targeted drug treatments and
      chromosomal translocations frequently involving the MLL, or ALL-1, gene. Two
      distinct mechanisms have been implicated as potential triggers of t-AML
      translocations: TOP2-mediated DNA cleavage and apoptotic higher-order chromatin
      fragmentation. Assessment of the role of TOP2 in this process has been hampered
      by a lack of techniques allowing in vivo mapping of TOP2-mediated DNA cleavage at
      nucleotide resolution in single-copy genes. A novel method, extension ligation
      mediated polymerase chain reaction (ELMPCR), was used here for mapping
      topoisomerase-mediated DNA strand breaks and apoptotic DNA cleavage across a
      translocation-prone region of MLL in human cells. We report the first genomic map
      integrating translocation breakpoints and topoisomerase I, TOP2, and apoptotic
      DNA cleavage sites at nucleotide resolution across an MLL region harboring a t
      AML translocation hotspot. This hotspot is flanked by a TOP2 cleavage site and is
      localized at one extremity of a minor apoptotic cleavage region, where multiple
      single- and double-strand breaks were induced by caspase-activated apoptotic
      nucleases. This cleavage pattern was in sharp contrast to that observed
      approximately 200 bp downstream in the exon 12 region, which displayed much
      stronger apoptotic cleavage but where no double-strand breaks were detected and
      no t-AML-associated breakpoints were reported. The localization and remarkable
      clustering of the t-AML breakpoints cannot be explained simply by the DNA
      cleavage patterns but might result from potential interactions between TOP2
      poisoning, apoptotic DNA cleavage, and DNA repair attempts at specific sites of
      higher-order chromatin structure in apoptosis-evading cells. ELMPCR provides a
      new tool for investigating the role of DNA topoisomerases in fundamental genetic
      processes and translocations associated with cancer treatments involving
      topoisomerase-targeted drugs.

PMID- 17033957
TI  - Generalized genomic distance-based regression methodology for multilocus
      association analysis.
AB  - Large-scale, multilocus genetic association studies require powerful and
      appropriate statistical-analysis tools that are designed to relate genotype and
      haplotype information to phenotypes of interest. Many analysis approaches
      consider relating allelic, haplotypic, or genotypic information to a trait
      through use of extensions of traditional analysis techniques, such as contingency
      table analysis, regression methods, and analysis-of-variance techniques. In this
      work, we consider a complementary approach that involves the characterization and
      measurement of the similarity and dissimilarity of the allelic composition of a
      set of individuals' diploid genomes at multiple loci in the regions of interest.
      We describe a regression method that can be used to relate variation in the
      measure of genomic dissimilarity (or "distance") among a set of individuals to
      variation in their trait values. Weighting factors associated with functional or
      evolutionary conservation information of the loci can be used in the assessment
      of similarity. The proposed method is very flexible and is easily extended to
      complex multilocus-analysis settings involving covariates. In addition, the
      proposed method actually encompasses both single-locus and haplotype-phylogeny
      analysis methods, which are two of the most widely used approaches in genetic
      association analysis. We showcase the method with data described in the
      literature. Ultimately, our method is appropriate for high-dimensional genomic
      data and anticipates an era when cost-effective exhaustive DNA sequence data can
      be obtained for a large number of individuals, over and above genotype
      information focused on a few well-chosen loci.

PMID- 17033958
TI  - Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome).
AB  - Mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal
      storage disorder caused by the inherited deficiency of the lysosomal membrane
      enzyme acetyl-coenzyme A: alpha -glucosaminide N-acetyltransferase (N
      acetyltransferase), which leads to impaired degradation of heparan sulfate. We
      report the narrowing of the candidate region to a 2.6-cM interval between D8S1051
      and D8S1831 and the identification of the transmembrane protein 76 gene (TMEM76),
      which encodes a 73-kDa protein with predicted multiple transmembrane domains and
      glycosylation sites, as the gene that causes MPS IIIC when it is mutated. Four
      nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6
      splice-site mutations, and 14 missense mutations were identified among 30
      probands with MPS IIIC. Functional expression of human TMEM76 and the mouse
      ortholog demonstrates that it is the gene that encodes the lysosomal N
      acetyltransferase and suggests that this enzyme belongs to a new structural class
      of proteins that transport the activated acetyl residues across the cell
      membrane.

PMID- 17033960
TI  - Test for interaction between two unlinked loci.
AB  - Despite the growing consensus on the importance of testing gene-gene interactions
      in genetic studies of complex diseases, the effect of gene-gene interactions has
      often been defined as a deviance from genetic additive effects, which is
      essentially treated as a residual term in genetic analysis and leads to low power
      in detecting the presence of interacting effects. To what extent the definition
      of gene-gene interaction at population level reflects the genes' biochemical or
      physiological interaction remains a mystery. In this article, we introduce a
      novel definition and a new measure of gene-gene interaction between two unlinked
      loci (or genes). We developed a general theory for studying linkage
      disequilibrium (LD) patterns in disease population under two-locus disease
      models. The properties of using the LD measure in a disease population as a
      function of the measure of gene-gene interaction between two unlinked loci were
      also investigated. We examined how interaction between two loci creates LD in a
      disease population and showed that the mathematical formulation of the new
      definition for gene-gene interaction between two loci was similar to that of the
      LD between two loci. This finding motived us to develop an LD-based statistic to
      detect gene-gene interaction between two unlinked loci. The null distribution and
      type I error rates of the LD-based statistic for testing gene-gene interaction
      were validated using extensive simulation studies. We found that the new test
      statistic was more powerful than the traditional logistic regression under three
      two-locus disease models and demonstrated that the power of the test statistic
      depends on the measure of gene-gene interaction. We also investigated the impact
      of using tagging SNPs for testing interaction on the power to detect interaction
      between two unlinked loci. Finally, to evaluate the performance of our new
      method, we applied the LD-based statistic to two published data sets. Our results
      showed that the P values of the LD-based statistic were smaller than those
      obtained by other approaches, including logistic regression models.

PMID- 17033959
TI  - Molecular population genetics of the gene encoding the human fertilization
      protein zonadhesin reveals rapid adaptive evolution.
AB  - A hallmark of positive selection (adaptive evolution) in protein-coding regions
      is a d(N)/d(S) ratio >1, where d(N) is the number of nonsynonymous
      substitutions/nonsynonymous sites and d(S) is the number of synonymous
      substitutions/synonymous sites. Zonadhesin is a male reproductive protein
      localized on the sperm head, comprising many domains known to be involved in cell
      cell interaction or cell adhesion. Previous studies have shown that VWD domains
      (homologous to the D domains of the von Willebrand factor) are involved directly
      in binding to the female zona pellucida (ZP) in a species-specific manner. In
      this study, we sequenced 47 coding exons in 12 primate species and, by using
      maximum-likelihood methods to determine sites under positive selection, we show
      that VWD2, membrane/A5 antigen mu receptor, and mucin-like domains in zonadhesin
      are rapidly evolving and, thus, may be involved in binding to the ZP in a species
      specific manner in primates. In addition, polymorphism data from 48 human
      individuals revealed significant polymorphism-to-divergence heterogeneity and a
      significant departure from equilibrium-neutral expectations in the frequency
      spectrum, suggesting balancing selection and positive selection occurring in
      zonadhesin (ZAN) within human populations. Finally, we observe adaptive evolution
      in haplotypes segregating for a frameshift mutation that was previously thought
      to indicate that ZAN was a potential pseudogene.

PMID- 17033961
TI  - Multipoint linkage analysis with many multiallelic or dense diallelic markers:
      Markov chain-Monte Carlo provides practical approaches for genome scans on
      general pedigrees.
AB  - Computations for genome scans need to adapt to the increasing use of dense
      diallelic markers as well as of full-chromosome multipoint linkage analysis with
      either diallelic or multiallelic markers. Whereas suitable exact-computation
      tools are available for use with small pedigrees, equivalent exact computation
      for larger pedigrees remains infeasible. Markov chain-Monte Carlo (MCMC)-based
      methods currently provide the only computationally practical option. To date, no
      systematic comparison of the performance of MCMC-based programs is available, nor
      have these programs been systematically evaluated for use with dense diallelic
      markers. Using simulated data, we evaluate the performance of two MCMC-based
      linkage-analysis programs--lm_markers from the MORGAN package and SimWalk2--under
      a variety of analysis conditions. Pedigrees consisted of 14, 52, or 98
      individuals in 3, 5, or 6 generations, respectively, with increasing amounts of
      missing data in larger pedigrees. One hundred replicates of markers and trait
      data were simulated on a 100-cM chromosome, with up to 10 multiallelic and up to
      200 diallelic markers used simultaneously for computation of multipoint LOD
      scores. Exact computation was available for comparison in most situations, and
      comparison with a perfectly informative marker or interprogram comparison was
      available in the remaining situations. Our results confirm the accuracy of both
      programs in multipoint analysis with multiallelic markers on pedigrees of varied
      sizes and missing-data patterns, but there are some computational differences. In
      contrast, for large numbers of dense diallelic markers, only the lm_markers
      program was able to provide accurate results within a computationally practical
      time. Thus, programs in the MORGAN package are the first available to provide a
      computationally practical option for accurate linkage analyses in genome scans
      with both large numbers of diallelic markers and large pedigrees.

PMID- 17033962
TI  - Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.
AB  - Epigenetic regulation of gene expression is a source of genetic variation, which
      can mimic recessive mutations by creating transcriptional haploinsufficiency.
      Germline epimutations and genomic imprinting are typical examples, although their
      existence can be difficult to reveal. Genomic imprinting can be tissue specific,
      with biallelic expression in some tissues and monoallelic expression in others or
      with polymorphic expression in the general population. Mutations in the skeletal
      muscle ryanodine-receptor gene (RYR1) are associated with malignant hyperthermia
      susceptibility and the congenital myopathies central core disease and
      multiminicore disease. RYR1 has never been thought to be affected by epigenetic
      regulation. However, during the RYR1-mutation analysis of a cohort of patients
      with recessive core myopathies, we discovered that 6 (55%) of 11 patients had
      monoallelic RYR1 transcription in skeletal muscle, despite being heterozygous at
      the genomic level. In families for which parental DNA was available, segregation
      studies showed that the nonexpressed allele was maternally inherited.
      Transcription analysis in patients' fibroblasts and lymphoblastoid cell lines
      indicated biallelic expression, which suggests tissue-specific silencing.
      Transcription analysis of normal human fetal tissues showed that RYR1 was
      monoallelically expressed in skeletal and smooth muscles, brain, and eye in 10%
      of cases. In contrast, 25 normal adult human skeletal-muscle samples displayed
      only biallelic expression. Finally, the administration of the DNA
      methyltransferase inhibitor 5-aza-deoxycytidine to cultured patient skeletal
      muscle myoblasts reactivated the transcription of the silenced allele, which
      suggests hypermethylation as a mechanism for RYR1 silencing. Our data indicate
      that RYR1 undergoes polymorphic, tissue-specific, and developmentally regulated
      allele silencing and that this unveils recessive mutations in patients with core
      myopathies. Furthermore, our data suggest that imprinting is a likely mechanism
      for this phenomenon and that similar mechanisms could play a role in human
      phenotypic heterogeneity.

PMID- 17033963
TI  - Distinct clinical phenotypes associated with a mutation in the mitochondrial
      translation elongation factor EFTs.
AB  - The 13 polypeptides encoded in mitochondrial DNA (mtDNA) are synthesized in the
      mitochondrial matrix on a dedicated protein-translation apparatus that resembles
      that found in prokaryotes. Here, we have investigated the genetic basis for a
      mitochondrial protein-synthesis defect associated with a combined oxidative
      phosphorylation enzyme deficiency in two patients, one of whom presented with
      encephalomyopathy and the other with hypertrophic cardiomyopathy. Sequencing of
      candidate genes revealed the same homozygous mutation (C997T) in both patients in
      TSFM, a gene coding for the mitochondrial translation elongation factor EFTs.
      EFTs functions as a guanine nucleotide exchange factor for EFTu, another
      translation elongation factor that brings aminoacylated transfer RNAs to the
      ribosomal A site as a ternary complex with guanosine triphosphate. The mutation
      predicts an Arg333Trp substitution at an evolutionarily conserved site in a
      subdomain of EFTs that interacts with EFTu. Molecular modeling showed that the
      substitution disrupts local subdomain structure and the dimerization interface.
      The steady-state levels of EFTs and EFTu in patient fibroblasts were reduced by
      75% and 60%, respectively, and the amounts of assembled complexes I, IV, and V
      were reduced by 35%-91% compared with the amounts in controls. These phenotypes
      and the translation defect were rescued by retroviral expression of either EFTs
      or EFTu. These data clearly establish mutant EFTs as the cause of disease in
      these patients. The fact that the same mutation is associated with distinct
      clinical phenotypes suggests the presence of genetic modifiers of the
      mitochondrial translation apparatus.

PMID- 17033964
TI  - Mutations of the mitochondrial holocytochrome c-type synthase in X-linked
      dominant microphthalmia with linear skin defects syndrome.
AB  - The microphthalmia with linear skin defects syndrome (MLS, or MIDAS) is an X
      linked dominant male-lethal disorder almost invariably associated with segmental
      monosomy of the Xp22 region. In two female patients, from two families, with MLS
      and a normal karyotype, we identified heterozygous de novo point mutations--a
      missense mutation (p.R217C) and a nonsense mutation (p.R197X)--in the HCCS gene.
      HCCS encodes the mitochondrial holocytochrome c-type synthase that functions as
      heme lyase by covalently adding the prosthetic heme group to both apocytochrome c
      and c(1). We investigated a third family, displaying phenotypic variability, in
      which the mother and two of her daughters carry an 8.6-kb submicroscopic deletion
      encompassing part of the HCCS gene. Functional analysis demonstrates that both
      mutant proteins (R217C and Delta 197-268) were unable to complement a
      Saccharomyces cerevisiae mutant deficient for the HCCS orthologue Cyc3p, in
      contrast to wild-type HCCS. Moreover, ectopically expressed HCCS wild-type and
      the R217C mutant protein are targeted to mitochondria in CHO-K1 cells, whereas
      the C-terminal-truncated Delta 197-268 mutant failed to be sorted to
      mitochondria. Cytochrome c, the final product of holocytochrome c-type synthase
      activity, is implicated in both oxidative phosphorylation (OXPHOS) and apoptosis.
      We hypothesize that the inability of HCCS-deficient cells to undergo cytochrome c
      mediated apoptosis may push cell death toward necrosis that gives rise to severe
      deterioration of the affected tissues. In summary, we suggest that disturbance of
      both OXPHOS and the balance between apoptosis and necrosis, as well as the X
      inactivation pattern, may contribute to the variable phenotype observed in
      patients with MLS.

PMID- 17033965
TI  - A chromosomal rearrangement hotspot can be identified from population genetic
      variation and is coincident with a hotspot for allelic recombination.
AB  - Insights into the origins of structural variation and the mutational mechanisms
      underlying genomic disorders would be greatly improved by a genomewide map of
      hotspots of nonallelic homologous recombination (NAHR). Moreover, our
      understanding of sequence variation within the duplicated sequences that are
      substrates for NAHR lags far behind that of sequence variation within the single
      copy portion of the genome. Perhaps the best-characterized NAHR hotspot lies
      within the 24-kb-long Charcot-Marie-Tooth disease type 1A (CMT1A)-repeats (REPs)
      that sponsor deletions and duplications that cause peripheral neuropathies. We
      investigated structural and sequence diversity within the CMT1A-REPs, both within
      and between species. We discovered a high frequency of retroelement insertions,
      accelerated sequence evolution after duplication, extensive paralogous gene
      conversion, and a greater than twofold enrichment of SNPs in humans relative to
      the genome average. We identified an allelic recombination hotspot underlying the
      known NAHR hotspot, which suggests that the two processes are intimately related.
      Finally, we used our data to develop a novel method for inferring the location of
      an NAHR hotspot from sequence variation within segmental duplications and applied
      it to identify a putative NAHR hotspot within the LCR22 repeats that sponsor
      velocardiofacial syndrome deletions. We propose that a large-scale project to map
      sequence variation within segmental duplications would reveal a wealth of novel
      chromosomal-rearrangement hotspots.

PMID- 17033966
TI  - Analysis of high-resolution HapMap of DTNBP1 (Dysbindin) suggests no consistency
      between reported common variant associations and schizophrenia.
AB  - DTNBP1 was first identified as a putative schizophrenia-susceptibility gene in
      Irish pedigrees, with a report of association to common genetic variation.
      Several replication studies have reported confirmation of an association to
      DTNBP1 in independent European samples; however, reported risk alleles and
      haplotypes appear to differ between studies, and comparison among studies has
      been confounded because different marker sets were employed by each group. To
      facilitate evaluation of existing evidence of association and further work, we
      supplemented the extensive genotype data, available through the International
      HapMap Project (HapMap), about DTNBP1 by specifically typing all associated
      single-nucleotide polymorphisms reported in each of the studies of the Centre
      d'Etude du Polymorphisme Humain (CEPH)-derived HapMap sample (CEU). Using this
      high-density reference map, we compared the putative disease-associated haplotype
      from each study and found that the association studies are inconsistent with
      regard to the identity of the disease-associated haplotype at DTNBP1.
      Specifically, all five "replication" studies define a positively associated
      haplotype that is different from the association originally reported. We further
      demonstrate that, in all six studies, the European-derived populations studied
      have haplotype patterns and frequencies that are consistent with HapMap CEU
      samples (and each other). Thus, it is unlikely that population differences are
      creating the inconsistency of the association studies. Evidence of association
      is, at present, equivocal and unsatisfactory. The new dense map of the region may
      be valuable in more-comprehensive follow-up studies.

PMID- 17033967
TI  - Mapping trait loci by use of inferred ancestral recombination graphs.
AB  - Large-scale association studies are being undertaken with the hope of uncovering
      the genetic determinants of complex disease. We describe a computationally
      efficient method for inferring genealogies from population genotype data and show
      how these genealogies can be used to fine map disease loci and interpret
      association signals. These genealogies take the form of the ancestral
      recombination graph (ARG). The ARG defines a genealogical tree for each locus,
      and, as one moves along the chromosome, the topologies of consecutive trees shift
      according to the impact of historical recombination events. There are two stages
      to our analysis. First, we infer plausible ARGs, using a heuristic algorithm,
      which can handle unphased and missing data and is fast enough to be applied to
      large-scale studies. Second, we test the genealogical tree at each locus for a
      clustering of the disease cases beneath a branch, suggesting that a causative
      mutation occurred on that branch. Since the true ARG is unknown, we average this
      analysis over an ensemble of inferred ARGs. We have characterized the performance
      of our method across a wide range of simulated disease models. Compared with
      simpler tests, our method gives increased accuracy in positioning untyped
      causative loci and can also be used to estimate the frequencies of untyped
      causative alleles. We have applied our method to Ueda et al.'s association study
      of CTLA4 and Graves disease, showing how it can be used to dissect the
      association signal, giving potentially interesting results of allelic
      heterogeneity and interaction. Similar approaches analyzing an ensemble of ARGs
      inferred using our method may be applicable to many other problems of inference
      from population genotype data.

PMID- 17033968
TI  - Mutation-positive and mutation-negative patients with Cowden and Bannayan-Riley
      Ruvalcaba syndromes associated with distinct 10q haplotypes.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) encodes a tumor
      suppressor phosphatase frequently mutated in both sporadic and heritable forms of
      human cancer. Germline mutations are associated with a number of heritable cancer
      syndromes that are jointly referred to as the "PTEN hamartoma tumor syndrome"
      (PHTS) and include Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus
      syndrome, and Proteus-like syndrome. Germline PTEN mutations have been identified
      in a significant proportion of patients with PHTS; however, there are still many
      individuals with classic diagnostic features for whom mutations have yet to be
      identified. To address this, we took a haplotype-based approach and investigated
      the association of specific genomic regions of the PTEN locus with PHTS. We found
      this locus to be characterized by three distinct haplotype blocks 33 kb, 65 kb,
      and 43 kb in length. Comparisons of the haplotype distributions for all three
      blocks differed significantly among patients with PHTS and controls (P=.0098,
      P<.0001, and P<.0001 for blocks 1, 2, and 3, respectively). "Rare" haplotype
      blocks and extended haplotypes account for two-to-threefold more PHTS chromosomes
      than control chromosomes. PTEN mutation-negative patients are strongly associated
      with a haplotype block spanning a region upstream of PTEN and the gene's first
      intron (P=.0027). Furthermore, allelic combinations contribute to the phenotypic
      complexity of this syndrome. Taken together, these data suggest that specific
      haplotypes and rare alleles underlie the disease etiology in these sample
      populations; constitute low-penetrance, modifying loci; and, specifically in the
      case of patients with PHTS for whom traditional mutations have yet to be
      identified, may harbor pathogenic variant(s) that have escaped detection by
      standard PTEN mutation-scanning methodologies.

PMID- 17033969
TI  - A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss
      (CATSHL) syndrome.
AB  - Activating mutations of FGFR3, a negative regulator of bone growth, are well
      known to cause a variety of short-limbed bone dysplasias and craniosynostosis
      syndromes. We mapped the locus causing a novel disorder characterized by
      camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL syndrome) to
      chromosome 4p. Because this syndrome recapitulated the phenotype of the Fgfr3
      knockout mouse, we screened FGFR3 and subsequently identified a heterozygous
      missense mutation that is predicted to cause a p.R621H substitution in the
      tyrosine kinase domain and partial loss of FGFR3 function. These findings
      indicate that abnormal FGFR3 signaling can cause human anomalies by promoting as
      well as inhibiting endochondral bone growth.

PMID- 17033970
TI  - PLA2G6 mutation underlies infantile neuroaxonal dystrophy.
AB  - Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive
      neurodegenerative disease that presents within the first 2 years of life and
      culminates in death by age 10 years. Affected individuals from two unrelated
      Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse
      cerebellar atrophy and abnormal iron deposition in the medial and lateral globus
      pallidum. Progressive white-matter disease and reduction of the N-acetyl
      aspartate : chromium ratio were evident on magnetic resonance spectroscopy,
      suggesting loss of myelination. The clinical and radiological diagnosis of INAD
      was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb
      locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP
      rs139897), and an underlying mutation common to both affected families was
      identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic,
      calcium-independent). These findings highlight a role of phospholipase in
      neurodegenerative disorders.

PMID- 17033971
TI  - Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with
      renal magnesium wasting, renal failure, and severe ocular involvement.
AB  - Claudins are major components of tight junctions and contribute to the epithelial
      barrier function by restricting free diffusion of solutes through the
      paracellular pathway. We have mapped a new locus for recessive renal magnesium
      loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of
      the claudin multigene family, in patients affected by hypomagnesemia, renal
      failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction
      protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules
      and the retina. The identified mutations interfere severely with either cell
      membrane trafficking or the assembly of the claudin-19 protein. The
      identification of CLDN19 mutations in patients with chronic renal failure and
      severe visual impairment supports the fundamental role of claudin-19 for normal
      renal tubular function and undisturbed organization and development of the
      retina.

PMID- 17033972
TI  - Detecting disease-causing mutations in the human genome by haplotype matching.
AB  - Comparisons between haplotypes from affected patients and the human reference
      genome are frequently used to identify candidates for disease-causing mutations,
      even though these alignments are expected to reveal a high level of background
      neutral polymorphism. This limits the scope of genetic studies to relatively
      small genomic intervals, because current methods for distinguishing potential
      causal mutations from neutral variation are inefficient. Here we describe a new
      strategy for detecting mutations that is based on comparing affected haplotypes
      with closely matched control sequences from healthy individuals, rather than with
      the human reference genome. We use theory, simulation, and a real data set to
      show that this approach is expected to reduce the number of sequence variants
      that must be subjected to follow-up analysis by at least a factor of 20 when
      closely matched control sequences are selected from a reference panel with as few
      as 100 control genomes. We also define a reference data resource that would allow
      efficient application of this strategy to large critical intervals across the
      genome.

PMID- 17033973
TI  - Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.
AB  - Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few
      cases have been described. We characterize 13 patients with DVD--5 with
      hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation
      interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of
      chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome
      (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available
      showed absence of a paternal copy of FOXP2. Five other individuals with deletions
      of paternally inherited FOXP2 but with incomplete clinical information or
      phenotypes too complex to properly assess are also described. Four of the
      patients with DVD also meet criteria for autism spectrum disorder. Individuals
      with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream
      of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction,
      we show the maternally inherited FOXP2 to be comparatively underexpressed. Our
      results indicate that absence of paternal FOXP2 is the cause of DVD in patients
      with SRS with maternal UPD7. The data also point to a role for differential
      parent-of-origin expression of FOXP2 in human speech development.

PMID- 17033974
TI  - Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal
      recessive cone dystrophy.
AB  - Retinal signal transmission depends on the activity of high voltage-gated l-type
      calcium channels in photoreceptor ribbon synapses. We recently identified a
      truncating frameshift mutation in the Cacna2d4 gene in a spontaneous mouse mutant
      with profound loss of retinal signaling and an abnormal morphology of ribbon
      synapses in rods and cones. The Cacna2d4 gene encodes an l-type calcium-channel
      auxiliary subunit of the alpha (2) delta type. Mutations in its human orthologue,
      CACNA2D4, were not yet known to be associated with a disease. We performed
      mutation analyses of 34 patients who received an initial diagnosis of night
      blindness, and, in two affected siblings, we detected a homozygous nucleotide
      substitution (c.2406C-->A) in CACNA2D4. The mutation introduces a premature stop
      codon that truncates one-third of the corresponding open reading frame. Both
      patients share symptoms of slowly progressing cone dystrophy. These findings
      represent the first report of a mutation in the human CACNA2D4 gene and define a
      novel gene defect that causes autosomal recessive cone dystrophy.

PMID- 17033976
TI  - [Retrospective comparative analysis of antidementia medication persistence
      patterns in Spanish Alzheimer's disease patients treated with donepezil,
      rivastigmine, galantamine and memantine].
AB  - INTRODUCTION AND AIM: Dementia of Alzheimer type has become the most frequent
      type of dementia in our environment. Treatment persistence is a crucial factor to
      delay patient functional and cognitive impairment. The aim of the present study
      was to determine treatment persistence in usual care settings with four different
      antidementia drugs: donepezil, rivastigmine, galantamine and memantine in a
      cohort of patients with Alzheimer's dementia in Spain. PATIENTS AND METHODS: An
      Alzheimer type dementia retrospective cohort study was performed in 13 Primary
      Care Health Centers in Spain. The study included patients treated between January
      2000 and March 2005. RESULTS: A total of 299 patients (44.8% female), mean age
      77.9 years, were included: 101 donepezil (33.8.%), 105 rivastigmine (35.1%), 51
      galantamine (17.1%) and 42 memantine (14.0%). Mean treatment duration was
      significantly different depending on therapy type, showing higher values for
      donepezil patients (mean: 83.3 weeks; 95% CI: 72.7-93.9) than for the other
      cholinesterase inhibitors: rivastigmine (mean: 76.6 weeks; 95% CI: 66.0-87.3),
      galantamine (mean: 65.8 weeks; 95% CI: 55.3-76.3) and memantine (60.9 weeks; 95%
      CI: 48.8-73.1), p = 0.049. Overall treatment persistence was significantly
      different between drugs, with again donepezil showing higher persistence (median
      time: 70.3 weeks; 95% CI: 49.8-90.7) than with the others drugs: rivastigmine
      (median time: 56.1 weeks; 95% CI: 36.1-76.2), galantamine (median time: 56.7
      weeks; 95% CI: 41.1-72.3) and memantine (median time: 52.1 weeks; 95% CI: 35.2
      69.1), log-rank = 10.16; p = 0.017. CONCLUSION: This study showed significative
      differences in the global treatment persistence among the considered drug
      cholinesterase inhibitors, showing higher persistence resulting in patients
      treated with donepezil compared to those who received rivastigmine, galantamine
      or memantine.

PMID- 17033975
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with
      mutations in the desmosomal gene desmocollin-2.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an
      inherited myocardial disorder associated with arrhythmias, heart failure, and
      sudden death. To date, mutations in four genes encoding major desmosomal proteins
      (plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2) have been implicated
      in the pathogenesis of ARVD/C. We screened 77 probands with ARVD/C for mutations
      in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. Two
      heterozygous mutations--a deletion and an insertion--were identified in four
      probands. Both mutations result in frameshifts and premature truncation of the
      desmocollin-2 protein. For the first time, we have identified mutations in
      desmocollin-2 in patients with ARVD/C, a finding that is consistent with the
      hypothesis that ARVD/C is a disease of the desmosome.

PMID- 17033977
TI  - [Internal structure of Dysfunctional Beliefs and Attitudes about Sleep Scale in a
      Spanish shift workers sample].
AB  - INTRODUCTION: Dysfunctional beliefs are some of the psychological factors that
      explains the origin and maintenance of insomnia. Morin developed a five
      theoretical dimension scale, the Dysfunctional Beliefs and Attitudes about Sleep
      Scale (DBAS), to assess them. AIMS: To analyze the internal structure of the
      Spanish version of DBAS, and to establish the differences on DBAS scores between
      two groups above described. SUBJECTS AND METHODS: The sample was 237 workers of
      those 197 were shift workers and the rest had a stable timetable (mean age =
      43.07; standard deviation = 9.39). The DBAS and the Pittsburgh Sleep Quality
      Index was administrated to them. RESULTS: The results of the items analysis and
      reliability of each five dimensions were moderate, except for the first and
      second dimension of Morin's proposal. Confirmatory factorial analysis isolated
      four factors: consequences of the insomnia on the diurnal yield/functioning
      (alpha = 0.75); control and prediction of the sleep (alpha = 0.70); consequences
      of the insomnia on the physical and mental health (alpha = 0.69), and
      expectations on the association sleep-age (alpha = 0.60). It was corroborated
      that either first, second or third factor allowed differentiating one group of
      another. CONCLUSIONS: All these results allowed us to consider Spanish version of
      DBAS as an appropriated 18 items adapted version. The structure of four factors
      is theoretically coherent, and it shows an adequate internal consistency and high
      capacity to differentiate well from bad sleepers.

PMID- 17033978
TI  - [Evaluation of autonomic cardiovascular functioning in patients with syncope].
AB  - INTRODUCTION: According to the current literature on the subject, patients with
      syncope suffer a dysfunction of the autonomic nervous system (ANS). Yet few
      studies offer a clear explanation of this dysfunction. Moreover, the evaluation
      of cardiovascular reflexes is a simple, useful method of studying the functional
      status of the ANS. This work was designed to evaluate the existence of
      dysautonomia in syncope patients by means of the autonomic cardiovascular
      stimulation tests; it has been the most comprehensive of those published to date.
      SUBJECTS AND METHODS: We studied 170 healthy volunteers and 188 patients with
      syncopes in the previous months, paired by age and sex. Cardiovascular
      stimulation tests were conducted, in accordance with Ewing and Clark's
      methodology, together with the cold test. A rating scale was included to evaluate
      the symptoms related to ANS involvement. RESULTS: Syncope patients display lower
      reactivity in tests involving cardiovascular stimulation of the ANS, regardless
      of whether they are taken individually or as a whole (67% in patients and 39% in
      controls) (p = 0.0001), except in the cold test. They also show an increase in
      the clinical symptoms of an autonomic origin (2.82 +/- 0.17) with respect to
      control subjects (0.78 +/- 0.09) (p = 0.0001). CONCLUSIONS: Our syncope patients
      have a dysautonomia that appears as a sympathetic and parasympathetic
      hypofunction. These findings confirm the value of autonomic cardiovascular
      stimulation tests in the study of these patients. Moreover, the search for other
      symptoms of autonomic involvement can be a great aid in evaluating this
      pathology.

PMID- 17033979
TI  - [Parkinsonism and Camptocormia with focal spinal myopathy: case report and
      responsiveness to treatment].
AB  - INTRODUCTION: Camptocormia is characterised by extreme flexion of the
      thoracolumbar spine. It suffered an increase during walking and it is relieved in
      supine position. Camptocormia has been described in psychogenic disorders, but in
      other diseases, including Parkinson's disease as well. It has been recently
      described several cases with focal spinal myopathy, and we present a patient with
      this clinical association. CASE REPORT: This 82-year-old man had a 6-year history
      of parkinsonian symptoms, mostly of rigid-akinetic type. He was in stage 4 on
      Hoehn & Yahr scale, and he had reached 62 points on Unified Parkinson Disease
      Rating Scale. Over the past 6-8 months, he developed progressive forward flexion
      of the trunk with clinical features of camptocormia. He suffered flogotic
      symptoms and signs on her lower back, and there were no dystonic posture or
      clinical features. Lumbar computerised tomography showed fat replacement of the
      paravertebral L3 muscles. A surgical paravertebral muscle examination and biopsy
      were performed, showing diffuse fat replacement and only a marginal myopathic
      focus. It was made several therapeutic approaches, with levodopa dose increase,
      reduction, fractioning, and addition of dopa-agonists. All of these strategies
      failed. It was determined to try a steroid course, but there were no improvement,
      so physiotherapy and rehabilitation measures did. He finally was confined to
      wheelchair. CONCLUSIONS: Physiopathologic and therapeutic aspects of camptocormia
      in Parkinson's disease are unclear. Their relationship could be casual or causal.
      Patients with clear inflammatory myopathy could benefit from steroid therapy, but
      patients with end-stage myopathy probably do not so.

PMID- 17033980
TI  - [Hypertrophic cranial and spinal pachymeningitis. A description of four new cases
      and a review of the literature].
AB  - INTRODUCTION: Hypertrophic pachymeningitis is an infrequent disease that is
      characterised by inflammatory hypertrophy of the dura mater. There are cranial,
      spinal and craniospinal forms of the disease. They may be due to underlying
      infectious, autoimmune or neoplastic processes, although most of the cases
      reported in recent years have no base pathology and are known as idiopathic
      hypertrophic pachymeningitis. The ideal treatment is unknown, but most cases
      usually respond well to therapy with corticoids. CASE REPORTS: We report two
      cases of cranial forms, one idiopathic with typical clinical features consisting
      in cranial polyneuropathy and good response to corticoids, and another case
      secondary to rheumatoid arthritis that began with epileptic seizures. Both had a
      parenchymatous oedema. The two forms of spinal pachymeningitis presented as
      progressive paraparesis that evolved well after surgical removal of the lesion.
      CONCLUSIONS: On observing pachymeningitis in neuroimaging tests it becomes
      necessary to conduct a comprehensive aetiological study in search of infectious,
      autoimmune and neoplastic diseases. In the cranial forms there may be
      parenchymatous oedema, which would explain the epileptic seizures and the
      cognitive deterioration of our patients. Response to corticoids is spectacular,
      although it is often necessary to continue to administer them for prolonged
      periods of time.

PMID- 17033981
TI  - [Imidazoline I(2) receptors as a possible marker for malignancy in human glial
      cell tumours].
AB  - AIM: To present the experimental data that support the hypothesis that the
      imidazoline I(2) receptors may be assessed as a biological marker to establish
      diagnosis and grade of human gliomas. DEVELOPMENT: Gliomas constitute the most
      important group of brain neoplasm in humans. In these tumours accurate
      histopathologic diagnosis is a first crucial prerequisite for patient treatment.
      However, current grading schemes are still limited by subjective histologic
      criteria. Therefore, the search for new molecular and biological markers of
      gliomas represents a crucial step. In this context, it has been reported a
      significant increase in I(2) density in human gliomas when compared with normal
      brain tissue and other intracranial non-glial tumours. Moreover, this increase
      seems to fit well with the degree of malignancy in human gliomas. Thus, in
      glioblastomas multiformes the I(2) density is 1.4 times higher than in anaplastic
      astrocytomas and 2.2 higher than in low-grade astrocytomas. CONCLUSIONS: The
      present results demonstrate that the measurement of the I(2) density by positron
      emission tomography techniques could be used in the future for grading and
      prognosis of human gliomas. This could avoid the current need for tumour biopsies
      in order to obtain a histopathologic diagnosis.

PMID- 17033982
TI  - [The pathophysiology of migraine. Reflections on the glutamatergic hypothesis].
AB  - INTRODUCTION AND DEVELOPMENT: Migraine is an episodic primary headache defined by
      its clinical characteristics. Several pathophysiological hypotheses have been put
      forward in an attempt to explain the mechanism by which headaches develop in
      patients suffering from migraine. We believe that there are enough data available
      to consider that in the cerebral cortex, and in certain situations, there may be
      either an alteration in the balance of glutamate in the extracellular space or
      generation of excitatory post-synaptic potentials at rest based on the activation
      of slightly increased AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid) and kainate receptors, which would account for the cortical
      hyperexcitability and the interictal changes observed in patients with migraine.
      CONCLUSIONS: Further knowledge about the mechanisms that start and trigger
      migraines is essential for the development of new therapeutic approaches.

PMID- 17033984
TI  - [Effects of bromazepam on motor learning: an electroencephalogram analysis based
      on the beta rhythm].

PMID- 17033985
TI  - [Fatal massive hemoptysis during thrombolysis of acute ischemic stroke].

PMID- 17033986
TI  - [Asymptomatic polymicrogyria].

PMID- 17033987
TI  - Sorbents: from bench to bedside. Can we combine membrane separation processes and
      adsorbent based solute removal?

PMID- 17033989
TI  - Biomaterials surface characterization and modification.
AB  - This paper presents several examples of recent work in the field of surface
      modification and characterization of biomaterials. Due to the explosion of
      techniques and approaches in this area, a complete review would be unmanageable
      in a single paper. Rather selected examples taken from such different areas as
      bone-contacting devices, drug eluting stents, and immobilization of novel
      biomolecules are presented. The aim is to place the existing and quickly
      developing background of analytical and synthetic biomaterial surface science
      into the current perspective of this rapidly evolving discipline.

PMID- 17033990
TI  - Novel membrane for guided bone regeneration.
AB  - Membranes have been clinically used for guided tissue and bone regeneration for
      decades, but their use in every day clinical practice is rather limited. We
      developed a biodegradable membrane (InionGTR) composed of polylactide,
      polyglycolide and trimethylene carbonate aiming to improve the properties of
      membrane. Before application the membrane is treated with N-methyl-pyrrolidone
      (NMP) to achieve a rubber like consistency, to allow easy handling and
      manageability in the clinical setting. After placing the membrane NMP diffuses
      out from the polymer phase into the water phase. The loss of NMP in the polymer
      stiffens the membrane up and allows space maintenance in the defect area. In
      addition the influx and efflux of NMP creates a porous surface on the membrane
      leading to an improved integration of tissues into the porous surface layers of
      the InionGTR membrane. Therefore, the use of NMP improves the handling in the
      clinical setting, and allows tissue integration and space maintenance, both
      important for the outcome of the treatment.

PMID- 17033991
TI  - 3D bone tissue growth in hollow fibre membrane bioreactor: implications of
      various process parameters on tissue nutrition.
AB  - New experimental evidence shows that hollow fibre membrane bioreactor (HFMB) may
      be applied to grow bulky bone tissues which may then be implanted into patients
      to repair skeletal defects. To design effective bone tissue engineering
      protocols, it is necessary to determine the quantitative relationships between
      the cell environment and tissue behaviour in HFMBs and their relationship with
      nutrient supply. It is also necessary to determine under what conditions
      nutritional limitations may occur and, hence, may cause cell death. These require
      that the appropriate bioreactor conditions for generating neotissues, and the
      nutrient transfer behaviour and chemical reaction during cell growth and
      extracellular matrix formation are studied thoroughly. In this paper, we aim to
      use an existing mathematical framework to analyse the influence of various
      relevant parameters on nutrient supply for bone tissue growth in HFMB. We adopt
      the well-known Krogh cylinder approximation of the HFMB. The model parameters
      (e.g., cell metabolic rates) and operating conditions for the mathematical model
      have been obtained from, or correspond to, in-house experiments with the
      exception of a few variables which have been taken from the literature. The
      framework is then used to study oxygen and glucose transport behaviour in the
      HFMB. Influence of a number of important process parameters, e.g., reaction
      kinetics, cell density, inlet concentration of nutrients, etc, on the nutrient
      distributions have been systematically analysed. The work presented in this paper
      provides insights on unfavourable system designs and specifications which may be
      avoided to prevent mass transfer limitations for growing bone tissues in HFMB.

PMID- 17033992
TI  - Quantitative constitutive behaviour and viscoelastic properties of fresh flexor
      tendons.
AB  - The objective of this study was to obtain detailed high quality experimental data
      under well-controlled test conditions in order to quantify tendon viscoelastic
      behaviour and provide an experimental basis for large deformation mathematical
      modelling. Eighty-six fresh chicken flexor digitorum profundus (FDP) tendons were
      mechanically tested using an Instron 5565 universal testing machine and a Bioplus
      bath containing physiological saline solution. At low strain rates (<or=0.001s(
      1)), no strain rate dependence was found and the value of the elastic modulus was
      324+/-17 MPa. At medium strain rates (0.003s(-1) - 0.1s(-1)), the elastic
      stiffness increased with increasing strain rate. For example, the values of the
      elastic modulus were 427+/-10, 653+/-21 and 837+/-11 MPa for strain rates of
      0.006s(-1), 0.012s(-1) and 0.05s(-1) respectively. A series of stress relaxation
      experiments at different levels of strain were conducted. The higher the initial
      stress level, the faster the stress relaxed. For all stress relaxation tests, the
      relationship of normalised relaxation function G(t) against log time (ln(t)) was
      approximately linear (R2 = 0.935 +/- 0.028) and this supports Fung's quasi-linear
      viscoelasticity (QLV) hypothesis. Some preliminary work on bovine flexor tendons
      using a video extensometer is also reported.

PMID- 17033993
TI  - Microdialysis for monitoring the process of functional tissue culture.
AB  - Continuous monitoring is important during tissue culture. However, there are
      still technical difficulties in monitoring the internal status of cells or
      tissues. In this paper, microdialysis is adopted to monitor functional tissue
      growth in a bioreactor. Explanted bovine caudal intervertebral disc (IVD) was
      used as the test tissue. A microdialysis membrane probe of 100 kDa molecular
      weight cut-off was employed and in situ calibration methods with phenol red and
      fluorescent 40 kDa dextran were developed to measure the relative recovery of the
      solute of interest, and membrane fouling, respectively. Tissue metabolism was
      monitored successfully. At the same time soluble macromolecules were picked up by
      the probe and were detected and quantified by Fast Protein Liquid Chromatography
      (FPLC) and/or Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS
      PAGE). These proteins were believed to be associated with biofunction of
      engineered tissue. Monitoring of phenol red content in the dialysate indicated
      that there was no significant fouling of the membrane probe during a 7-day
      culture period and the Relative Recovery of macromolecules of interests remained
      roughly 9%. We concluded that microdialysis could be used to sample a wide range
      of molecular species released during cell metabolism and extracellular matrix
      turnover, which were direct or indirect indications of cell and tissue functions.
      The application of the developed system could be extended to monitor tissue
      repair in vivo, and the development of the engineered tissue.

PMID- 17033994
TI  - Surface and hemocompatibility studies of bi-soft segment polyurethane membranes.
AB  - Cross-linked urethane/urea membranes with two soft segments were prepared by
      extending a poly(propylene oxide) based tri-isocyanate-terminated prepolymer
      (PUR) with polybutadiene diol (PBDO). The ratio of prepolymer and polybutadiene
      diol was varied to yield cross-linked membranes with different compositions,
      exhibiting different degrees of phase-separation of the PBDO segments in the bulk
      and of surface enrichment in PUR. In this work, surface energy and
      hemocompatibility aspects (hemolysis and thrombosis) of the PUR/PBDO membranes
      were evaluated. The results showed that the membrane surface energy increased
      with the PBDO content until 25% of PBDO, and decreased thereafter. The
      introduction of the second, more hydrophobic, soft segment (PBDO) in the PUR
      membranes turned hemolytic into non-hemolytic membranes and, for a blood-material
      contact time of 10 minutes, decreased the thrombogenicity significantly. The 10%
      PBDO membrane was the least thrombogenic and was also non-hemolytic. The
      hemolysis degree did not vary significantly with the PBDO content while, for
      blood-material contact times of 10 minutes, the thrombogenicity increased with an
      increase in PBDO content above 10%. Membrane thrombogenicity varied with the
      blood-material contact time. For blood contact times of 10 minutes, all membranes
      tested were less thrombogenic than glass.

PMID- 17033995
TI  - Attachment and growth of fibroblasts on poly(L-lactide/epsilon-caprolactone)
      scaffolds prepared in supercritical CO2 and modified by polyethylene imine
      grafting with ethylene diamine-plasma in a glow-discharge apparatus.
AB  - In this study, a copolymer of L-lactide and epsilon-caprolactone (Mn: 73,523, Mw:
      127,990 and PI: 1.74) was synthesized by ring-opening polymerization by using
      stannous octoate as the catalyst. FTIR, 1H-NMR and DSC confirmed the copolymer
      formation. The copolymer films were prepared and a novel method was developed to
      produce highly porous sponges for potential use in tissue engineering. Films were
      subjected to supercritical CO2 at 3300 psi and 70 degrees C to create porous
      structures for production of possible tissue engineering scaffolds. The pore
      sizes were in the range of 40-80 microm. The copolymer films were pre-wetted with
      polyethylene imine (PEI) and then treated with ethylene diamine (EDA)-plasma in
      glow-discharge apparatus. Gas plasma surface modification of three-dimensional
      scaffolds fabricated by supercritical carbon dioxide technique was demonstrated
      to enhance cell adhesion, proliferation, and differentiation over 6 days in
      culture using L929 fibroblast cell line. Alkaline phosphatase (ALP) activity and
      glucose uptake in cell culture medium were followed in the cell culture
      experiments. Fibroblastic cell attachment and growth on the EDA-plasma treated
      scaffolds were rather low. However, both cell attachment and growth were
      significantly increased by PEI pre-treatment before EDA-plasma. The changes in
      ALP activity and glucose uptake also supported the cell growth behavior on these
      PEI and EDA-plasma treated scaffolds.

PMID- 17033996
TI  - Physical-chemical and biological characterization of silk fibroin-coated porous
      membranes for medical applications.
AB  - Membranes in artificial organs and scaffolds for tissue engineering are often
      coated with biomimetic molecules (e.g., collagen) to improve their
      biocompatibility and promote primary cell adhesion and differentiation. However,
      animal proteins are expensive and may be contaminated with prions. Silk fibroin
      (SF) made by Bombyx Mori silk worms, used as a scaffold or grafted to other
      polymers, reportedly promotes the adhesion and growth of many human cell types.
      This paper describes how commercial porous membranes were physically coated with
      SF, and their physical-chemical properties were characterized by SEM, AFM,
      tensile stress analysis and dynamic contact angle measurements. The effect of the
      SF coating on membrane biocompatibility and resistance to bacterial colonization
      is also examined. The proposed technique yields SF coats of different thickness
      that strengthen the membranes and make their surface remarkably more wettable.
      The SF coat is not cytotoxic, and promotes the adhesion and proliferation of an
      immortalized fibroblast cell line. Similarly to collagen, SF-coated membranes
      also exhibit a much better resistance to the adhesion of S. epidermidis bacteria
      than uncoated membranes. These preliminary results suggest that SF is a feasible
      alternative to collagen as a biomimetic coating for 3D scaffolds for tissue
      engineering or bioartificial (as well as artificial) prosthesis.

PMID- 17033997
TI  - Histomorphometric analysis of poly-L/D-lactide 96/4 sutures in the gastrocnemius
      tendon of rabbits.
AB  - BACKGROUND: Common Achilles tendon ruptures are not usually fixed by
      bioabsorbable sutures due to limitations in their strength retention properties.
      Modern technology has made it possible to develop bioabsorbable sutures with
      prolonged strength retention. AIMS: To evaluate histologically tissue reactions
      of poly-L/D-lactide (PLDLA) sutures implanted in Achilles tendon of rabbits.
      MATERIAL AND METHODS: Fifteen rabbits were evaluated at 2, 6 and 12 weeks
      postoperatively, with five rabbits in each follow-up group. PLDLA monofilament
      sutures were implanted into the medial gastrocnemius tendon. Polyglyconate
      monofilament sutures with similar diameter (Maxon 4-0, Cyanamid of Great Britain
      Ltd., Gosport, UK) were implanted in the contralateral gastrocnemius tendon. The
      histology was studied in hard-resin embedded samples. The thickness of the formed
      fibrous tissue capsule was determined histomorphometrically. RESULTS: PLDLA led
      to formation of significantly thinner fibrous tissue capsule than Maxon sutures
      of the same diameter. Median thickness (PLDLA vs. Maxon) at two weeks was 5.26
      vs.13.22 microm, at six weeks 11.66 vs. 80.97 microm, and at 12 weeks 10.63 vs.
      17.59 microm (p<0.01). CONCLUSIONS: During the 12 week follow-up period, PLDLA
      sutures implanted intratendineously formed thinner fibrous capsule than Maxon
      sutures of the same diameter. The suture materials were not totally absorbed by
      12 weeks.

PMID- 17033998
TI  - Molecular recognition based iron removal from human plasma with imprinted
      membranes.
AB  - The aim of this study is to prepare ion-imprinted poly(2-hydroxyethyl
      methacrylate) (HEMA) based membranes which can be used for the selective removal
      of Fe3+ ions from Fe3+-overdosed human plasma. N-methacryloyl-(L)-glutamic acid
      (MAGA) was chosen as the ion-complexing monomer. In the first step, Fe3+ was
      complexed with MAGA and then, the Fe3+-imprinted poly(HEMA-MAGA) membranes were
      prepared by UV-initiated photo-polymerization of HEMA and MAGA-Fe3+ complex in
      the presence of an initiator (benzoyl peroxide). After that, the template (i.e.,
      Fe3+ ions) was removed by using 0.1 M EDTA solution at room temperature. The
      specific surface area of the Fe3+-imprinted poly(HEMA-MAGA) membranes was found
      to be 49.2 m2/g and the swelling ratio was 92%. According to the elemental
      analysis results, the polymeric membranes contained 145.7 micromol MAGA/g
      polymer. The maximum adsorption capacity was 164.2 micromol Fe3+/g membrane. The
      relative selectivity coefficients of ion-imprinted membranes for Fe3+/Zn2+ and
      Fe3+/Cr3+ were 12.6 and 62.5 times greater than the non-imprinted matrix,
      respectively. The Fe3+-imprinted poly(HEMA-MAGA) membranes could be used many
      times without decreasing their Fe3+ adsorption capacities significantly.

PMID- 17033999
TI  - An experimental pilot study on controlled portal vein arterialization with an
      extracorporeal device in the swine model of partial liver resection and ischemia.
AB  - AIM: To determine whether the physiologically oxygenated arterial blood reversed
      in the portal system by means of portal vein arterialization (PVA) through an
      extracorporeal device which we have called L.E.O2.NARDO (Liver Extracorporeal
      Oxygen. NARDO) is effective in treating swine with subtotal hepatectomy leading
      to acute liver failure (ALF). METHODS: Ten swine with ALF induced by 85-90% liver
      resection and five minutes of ischemia-reperfusion injury were randomly divided
      into two groups: five animals received PVA extracorporeal treatment and five
      swine were not-treated (control group). Blood was withdrawn from the iliac artery
      and reversed in the portal venous system. An extracorporeal device was interposed
      between the outflow and the inflow in order to monitoring the hemodynamic
      parameters. Each treatment lasted 6 hours. Serum and liver samples were collected
      in both groups. The survival was assessed at 1 week. RESULTS: The PVA
      extracorporeal treatment yielded beneficial effects for subtotal hepatectomy
      induced ALF swine with decreased serum ammonia, transaminases and total bilirubin
      as compared with the untreated group. INR recovered rapidly in the PVA
      extracorporeal group remaining significantly lower than in untreated animals. The
      7-day survival of PVA-extracorporeal group swine was significantly higher than
      that of untreated animals, with a statistically significant difference (p<0.05).
      Four swine in the PVA-extracorporeal group survived at 1 week while none of the
      swine in the control group were alive at that time; an average time of 144h+/-13h
      and 24.4h+/-5h was observed in the PVA-extracorporeal and control groups,
      respectively. CONCLUSIONS: Arterial blood supply in the portal system through the
      extracorporeal device is easily applicable, efficacious, safe and may represent a
      novel approach for ALF swine induced by subtotal liver resection.

PMID- 17034000
TI  - Enhancement of osteoblast gene expression by mechanically compatible porous Si
      rich nanocomposite.
AB  - Synthesis of a porous bioactive ceramic implant for load bearing applications is
      a challenging task in maxillofacial and orthopedic surgeries. A novel bioactive
      resorbable silica-calcium phosphate nanocomposite (SCPC) has recently been
      introduced as a potential bone graft. In the present study, we employed SCPC to
      develop a resorbable porous scaffold and analyzed the effects of composition and
      porosity on the mechanical properties. The ranges of compressive strength and
      modulus of elasticity of SCPC containing 32-56% porosity were 1.5-50 MPa and 0.14
      2.1 GPa, respectively, which matched the corresponding values for trabecular
      bone. The compressive strength of dense SCPC was dependent on the Si content and
      acquired values (93-285 MPa) comparable to that of cortical bone. The superior
      mechanical properties of SCPC are attributed to the intricate interactions at the
      boundaries of the nanograins and to the homogenous distribution of hierarchical
      pore-structure throughout the material volume. X-ray computed tomography and
      mercury porosimetry analyses revealed high interconnectivity of the pores in the
      size range 3 nm to 650 microm. Quantitative real-time PCR analyses showed that
      neonatal rat calvarial osteoblasts attached to Si-rich SCPC expressed 5- and 26
      fold higher osteocalcin mRNA levels compared to cells attached to ProOsteon
      hydroxyapatite disks and tissue culture polystyrene plates respectively, after
      four days in culture. Results of the present study strongly suggest that porous,
      bioactive resorbable SCPCs can serve as tissue engineering scaffolds for cell
      delivery to treat load-bearing bone defects in orthopedic and maxillofacial
      surgeries.

PMID- 17034001
TI  - Microfabrication of fractal polymeric structures for capillary morphogenesis:
      applications in therapeutic angiogenesis and in the engineering of vascularized
      tissue.
AB  - Microfabrication techniques were combined with fractal algorithms to realize
      polymeric scaffolds resembling capillary networks. The scaffolds were seeded with
      human endothelial cells in monoculture as well as in coculture with human
      fibroblasts. To enhance the process of angiogenesis, endothelial cells were
      transfected with an adenoviral vector carrying the gene for human tissue
      kallikrien. The results demonstrate that both the presence of a structured
      scaffold as well as fibroblasts in coculture contribute synergically to the
      promotion of a metabolically active network. The fractal scaffolds have several
      possible applications for example in vascularized tissue engineering and
      therapeutic angiogenesis. A broader implication of these results is that cell
      extra cellular matrix and cell-cell interactions cooperate dynamically both at a
      biochemical as well as microstructural level.

PMID- 17034002
TI  - Blood permeability of a novel ceramic scaffold for bone morphogenetic protein-2.
AB  - A functionally graded apatite (fg-HAp) with body fluid permeability was developed
      from bovine bone. The tissue reaction of fg-HAp and its efficacy as a scaffold
      for recombinant human bone morphogenetic protein-2 (BMP-2) were evaluated
      histomorphometrically, and a component of permeable fluid into the fg-HAp was
      analyzed by immunoblotting assay. The fg-HAp block (27 mm(3)) combined with and
      without BMP-2 (5 microg) was implanted subcutaneously in 4-week-old Wistar rats.
      Histological examination showed that the surface and bulk degradations of the fg
      HAp proceeded extensively and giant cells appeared on the fg-HAp at 2 weeks. Body
      fluid permeation was found inside the fg-HAp, and the fluid component was
      immunopositive for albumin. In addition, albumin was detected as a main component
      among proteins collected from the in vivo implanted fg-HAp. The bioabsorption of
      the fg-HAp was accelerated as BMP-2-induced bone matured. Histomorphometrical
      analysis at 4 weeks in the BMP-2/fg-HAp implant showed 59.0% in the total volume
      of bone and marrow. These results indicate that fg-HAp is an innovative,
      bioabsorbable bioceramic with fluid permeability characteristic, and may become a
      biointegrated scaffold for bone engineering.

PMID- 17034003
TI  - Biological activity of tri-calciumphosphate/hydroxyl-apatite granules mixed with
      impacted morsellized bone graft. A study in rabbits.
AB  - Reconstruction of bone defects with impacted morsellized cancellous bone grafts
      (MCB) is a popular method. Because of a shortage of human bone, mixing with
      biomaterials may be attractive. Ceramics may be used as bone graft extenders. In
      this study, various volume mixtures of biphasic tri-calciumphosphate/hydroxyl
      apatite (TCP-HA) granules (1.5-2 mm) with MCB were examined in a non-loaded
      defect model in rabbits. Direct post-operatively, many 10-150 microm TCP-HA
      particles were present due to impaction. Irrespective to the group, after 8
      weeks, virtually all MCB was resorbed and most TCP-HA granules were osseous
      integrated with newly formed bone. The cross-sectional areas of TCP-HA after 8
      weeks was generally smaller compared with direct post-operatively and the number
      of small 10-150 microm TCP-HA particles seemed reduced. Macrophages and giant
      cells were sparse after 8 weeks. In conclusion, the osteoconductivity of various
      mixtures of MCB and TCP-HA granules is not dependent on the ratio of TCP-HA over
      MCB. The reduced number of the 10-150microm TCP-HA particles after 8 weeks, may
      suggest that a cellular mediated resorption process of TCP-HA granules took
      place. Based on these favorable biological findings subsequent in-vivo
      experiments are warranted in load-bearing conditions to investigate whether these
      findings hold for joint reconstruction purposes.

PMID- 17034004
TI  - Accelerating aging of zirconia femoral head implants: change of surface structure
      and mechanical properties.
AB  - Recently, alternations of zirconia ceramic femoral heads of total hip prostheses
      during in vivo conditions have caused concern in the medical disciplines
      regarding phase transformation of zirconia prosthetic components. In this paper,
      we have investigated the mechanical and structural properties of different
      laboratory aged zirconia femoral heads and correlated changes in mechanical
      properties with the phase compositions of the sample. From laser microscope
      observation, cross-sectional Scanning electron microscopy imaging, and X-ray
      diffraction analysis on the surface of the zirconia femoral heads, we found
      monoclinic to tetragonal phase transformation in zirconia prostheses over time
      during the aging process in the laboratory. Mechanical properties, mainly
      hardness (H) and Young's modulus (E) values, were measured by nanoindentation
      technique on the surface of these implants. The results showed that both H and E
      values decreased with increased monoclinic phase in zirconia, thus confirming a
      phase transformation over time during aging.

PMID- 17034005
TI  - Persistence problem in schizophrenia and mitochondrial DNA.
AB  - Schizophrenia, a major psychosis with a strong genetic component, persists over
      generations despite a clearly reduced reproductive fitness of the patients. This
      'persistence' problem has puzzled scientists for long years. A hypothesis of
      'balanced polymorphism' proposed by Huxley et al. that the incidence could be
      sustained by a higher fertility in the siblings of the patients has not been
      supported by most epidemiological studies. Multiple-genes model, which most
      geneticists today accept, explains that the loss of susceptibility alleles
      resulting from the lower fertility of the patients would have a negligible effect
      on the overall gene pool in the population. We carefully examined the multiple
      genes model and proved it cannot account for the persistence problem without
      unrealistic assumptions and hence the contribution of multiple genes in the
      nuclear DNA to the heredity of schizophrenia should be considerably limited. We
      demonstrated a pathogenic gene with a low penetrance, if located in the
      mitochondrial DNA, could be sustained given a higher fertility of the 'female'
      siblings and/or a decreased male-female ratio in the offspring of the susceptible
      females. This hypothesis, coupled with the report which suggests mitochondrial
      dysfunction in schizophrenia, may encourage a new direction in genetic study of
      this puzzling disorder.

PMID- 17034006
TI  - Effect of quetiapine in psychotic Parkinson's disease patients: a double-blind
      labeled study of 3 months' duration.
AB  - This double-blind randomized study examined the effect of quetiapine (QTP) on
      drug-induced psychosis (DIP) in Parkinson's disease (PD). Conventional
      antipsychotic drugs are associated with adverse extrapyramidal effects. QTP is a
      new atypical antipsychotic drug used in the treatment of psychosis in PD. A total
      of 58 consecutive psychotic PD patients (mean age, 75 +/- 8.3 years; mean disease
      duration, 10.5 +/- 6.4 years; 29 with dementia) were randomly assigned to 2
      groups: 30 were treated with QTP (mean dose, 119.2 +/- 56.4 mg) and 28 received
      placebo for 3 months. The motor part of the Unified Parkinson's Disease Rating
      Scale, the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the
      Hamilton Rating Scale for Depression, the Epworth Sleepiness Score, and the
      Clinical Global Impression Scale were administered before and during the study.
      No significant difference was found between the groups in all parameters. There
      were 32 PD patients (55%) completed the 3-month study (15 [26%] QTP and 17 [29%]
      placebo). Treatment was interrupted in 15 patients in the QTP and 11 in the
      placebo groups. This double-blind study did not show a beneficial effect of QTP
      for the treatment of DIP in PD. The high rate of withdrawal probably influenced
      the results. Larger double-blind studies are required.

PMID- 17034007
TI  - Follow-up mapping supports the evidence for linkage in the candidate region at
      9q22 in the NIMH Alzheimer's disease Genetics Initiative cohort.
AB  - Other than the APOE peak at 19q13, the 9q22 region was identified in our original
      genomic scan as the candidate region with the highest multipoint lod score (MLS)
      in the subset of late onset Alzheimer's Disease (AD) families (MLS = 2.9 at 101
      cM) from the NIMH Genetics Initiative sample. We have now genotyped an additional
      12 short tandem repeats (STR) in this region. Multipoint analysis shows the
      region remains significant with an increase in the peak MLS from 2.9 to 3.8 at 95
      cM near marker D9S1815, and the 1 LOD interval narrows from 21.5 to 11 cM. HLOD
      scores also provide evidence for significant linkage (4.5 with an alpha = 31%)
      with a further narrowing of the region to 6.6 cM (92.2-98.8 cM). Single
      nucleotide polymorphisms (SNPs) in the Ubiquilin1 gene (UBQLN1), located at 83.3
      cM, have been reported to be significantly associated to AD, accounting for a
      substantial portion of the original linkage signal [Bertram et al., 2005]. Our
      analyses of the higher resolution genotype data generated here provide further
      support for the existence of a least one additional locus on chromosome 9q22. In
      an effort to pinpoint this putative AD susceptibility gene, we have begun to
      analyze SNPs in other candidate genes in and around this narrowed region to test
      for additional associations to AD.

PMID- 17034008
TI  - Glutathione S-transferase polymorphisms and onset age in alpha-synuclein A53T
      mutant Parkinson's disease.
AB  - Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine
      mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has
      detoxification and antioxidative functions. To screen genetic variations in GST
      for an effect on the onset age (OA) of PD, we typed seven common genetic
      polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected
      individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1)
      mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that
      of idiopathic PD. Our allelic analysis showed that the subjects homozygous for
      the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA
      acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years,
      n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year
      acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs.
      46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined,
      both results lose statistical significance. Nevertheless, our results suggest
      that further investigation in GSTP1 variants and PD pathogenesis is warranted in
      sporadic PD and that a search for toxins that accelerate PD OA should pay
      particular attention to GST-P1 substrates.

PMID- 17034009
TI  - Mutation screen of the GAD2 gene and association study of alcoholism in three
      populations.
AB  - Synaptic actions of gamma-amino butyric acid (GABA) have been implicated in many
      facets of ethanol's effects and risk for alcoholism. We examined whether
      variation in glutamate decarboxylase-2 (GAD2), a gene encoding for a major enzyme
      in the synthesis of GABA, contributes to risk of alcohol dependence (AD). We
      screened GAD2 for sequence variants using dHPLC in a population of 96
      individuals. Several single nucleotide polymorphisms (SNPs), including four rare
      non-synonymous polymorphisms, were identified. Thirteen SNPs located in the GAD2
      gene were genotyped in a sample of 113 Russian males with AD and 100 Russian male
      controls. These analyses revealed a modest association between the functional
      GAD2 -243 A > G SNP (rs2236418) and AD (allele P = 0.038, genotype P = 0.008). An
      additional sample of 138 Russian males with AD were genotyped for the GAD2 -243 A
      > G. These analyses supported an association of this polymorphism with AD
      (combined sample allele P = 0.038, genotype P = 0.0009). We extended these
      findings to additional populations: a sample of 538 college students assessed
      using the AUDIT and a sample of European-American (EA) AD subjects (n = 235) and
      controls (n = 310). Analyses in these populations did not support a role for GAD2
      in alcoholism. In summary, the results of an extensive search for an association
      of GAD2 with AD suggest that variation in GAD2 is not a major risk factor for AD
      in EAs. The functional promoter GAD2 -243 A > G variant may influence risk for AD
      in some populations, or its role may be limited to susceptibility to severe AD.

PMID- 17034010
TI  - Effect of oxygen inhibition on composite repair strength over time.
AB  - The study was aimed at examining whether an oxygen inhibition layer is required
      for bonding a repairing to a pre-existing composite, and to determine the time
      required for free radicals within a composite substrate to decay to the extent
      that the composite repair strength drops significantly. Ten slabs of Gradia
      Direct Anterior (GC Corp.) were divided into (1) control group: an interfacial
      oxygen inhibition layer was created by applying and light-curing two layers of
      bonding resin (D/E Resin, Bisco) to the slabs surface in atmospheric air; (2)
      experimental group: the absence of an interfacial oxygen inhibition layer was
      obtained by light-curing the second bonding resin layer in a nitrogen atmosphere.
      After 1 and 2 h, 1, 14, and 30 days of air storage, a composite repair was
      layered over the bonding resin. Microtensile bond strengths were measured and
      statistically analyzed. The curing atmosphere was not a significant factor for
      bond strength (p = 0.82), and time and curing atmosphere-time interaction were
      significant (p < 0.001). The 30 day-strengths were the lowest (p < 0.05). An
      oxygen-inhibited layer is not initially required for bonding to resin composite,
      and it takes more than 14 days before the bond strength between a pre-existing
      and a fresh composite drops.

PMID- 17034011
TI  - CO2 laser-induced zonation in dental enamel: a Raman and IR microspectroscopic
      study.
AB  - The gradient of structural alteration and molecular exchange across CO(2) laser
      irradiated areas in dental enamel was analyzed by Raman and attenuated total
      reflectance infrared microspectroscopy. The type and the degree of structural
      changes in morphologically distinguishable zones within the laser spot vary
      depending on the laser-irradiation parameters--power (1 and 3 W), treatment time
      (5 and 10 s), and operational mode (super pulse and continuous wave). Using
      higher power, irrespective of the operation mode, the enamel tissue ablates and a
      crater is formed. The prevalent phase at the bottom of the crater is dehydrated
      O(2) (2-)-bearing apatite, that is, the fundamental framework topology is
      preserved. Additional nonapatite calcium phosphate phases are located mainly at
      the slope of the laser crater. No structural transformation of mineral component
      was detected aside the crater rim, only a CO(3)-CO(2) exchange, which decays with
      the radial distance. A lower-power laser irradiation slightly roughens the enamel
      surface and the structural modification of enamel apatite is considerably weaker
      for continuous wave than for super pulse mode. Prolonged low-power laser
      treatment results in recrystallization, and thus structural recovering of apatite
      might be of clinical relevance for enamel surface treatments.

PMID- 17034012
TI  - Evaluation of bone regeneration at critical-sized calvarial defect by DBM/AM
      composite.
AB  - This study investigated the bone-regenerative potential of a demineralized bone
      and acellular matrix (DBM/AM) composite (AlloCraft DBM) in comparison with
      autologous bone using an in vivo model. Critical-sized calvarial defects (5 mm)
      were created in athymic rats. The defects were grafted with either the DBM/AM
      composite or the acellular human dermal matrix (AM), and compared with the
      defects filled with autologous bone (positive control) and the empty defect
      (negative control). Histological and radiographic assessments were carried out at
      4 and 8 weeks after surgery to determine the biological healing, the amount and
      type of new bone formation and the percentage of new bone filled in the critical
      defects. At 4 weeks, DBM/AM composite group had the highest percentage of the
      defect filled with new bone (84%), which was significantly greater than
      autologous bone (62%), AM (41%), and untreated control (32%) groups. At 8 weeks,
      the DBM/AM continued to have the highest percentage of the defect filled with new
      bone (91%). The autologous bone group increased the percentage of bone fill to
      83%. The defects either filled with AM or left untreated still had less of the
      defect filled with new bone, 57% and 33%, respectively. The total healing of
      defects grafted with DBM/AM was comparable with autologous bone group at 8 weeks.
      The results demonstrated that the DBM/AM composite promoted new bone formation
      more rapidly than autologous bone at calvarial defect in athymic rats. The study
      supports that DBM/AM is a potential substitute of autologous bone for bone
      repair.

PMID- 17034013
TI  - Influence of changes in the composition of an acrylic bone cement on its
      polymerization kinetics.
AB  - It has been suggested in the literature that a lower polymerization rate of an
      acrylic bone cement is favorable for the in vivo longevity of a cemented
      arthroplasty. The present work was a study of the influence of three changes in
      the composition of an acrylic bone cement (when taken separately) on the cement
      polymerization rate at 37 degrees C (assumed to be the temperature in the bone
      bed during a cemented arthroplasty) [k']. The changes were the amount of
      copolymer as a proportion of the total powder weight (in cements in which there
      is a copolymer in the powder), the amount of DMPT as a proportion of the total
      volume of the liquid monomer, and the accelerator. k' was calculated using values
      of the activation energy and the frequency factor (assuming the polymerization
      reaction is Arrhenius in nature) that were computed from measurements made using
      the nonisothermal mode of differential scanning calorimetry. Statistical analysis
      (one-way ANOVA, with Bonferroni correction, and factorial ANOVA) of the k' values
      showed that the change in accelerator had a significant influence on k'. The
      importance of this finding, together with results from two relevant literature
      reports, is discussed within the context of the use of modified bone cements in
      cemented arthroplasties.

PMID- 17034014
TI  - Environmental degradation of glass-ionomer cements: a depth-sensing
      microindentation study.
AB  - This study investigated the effects of various environmental conditions on the
      hardness and elastic modulus of restorative glass-ionomer cements (GICs). Two
      resin-modified GICs (RMGICs) (Fuji II LC [FL]; Photac-Fil Quick [PQ]) and three
      highly viscous GICs (HVGICs) (Fuji IX Fast [FN]; KetacMolar [KM]; KetacMolar
      Quick [KQ]) were evaluated in this study. Specimens were fabricated according to
      the manufacturers' instructions and stored under a variety of conditions (n = 7):
      100% humidity, distilled water, pH 5 demineralization solution, and pH 7
      remineralization solution. The hardness and elastic modulus were measured using a
      depth-sensing microindentation test after 4 weeks. The results were analyzed
      using the independent samples T-test and ANOVA/Scheffe's post hoc test (p <
      0.05). HVGICs showed significantly higher hardness and elastic modulus than
      RMGICs under all storage conditions. Storage in distilled water significantly
      increased the hardness and elastic modulus of FN, but decreased that of PQ. All
      HVGICs and RMGICs stored in remineralization solution had hardness values and
      elastic moduli comparable to those stored in water. Compared to remineralization
      solution, demineralization solution had no significant effects on the modified
      GICs with the exception of KQ. The results suggest that the mechanical properties
      of glass-ionomer restoratives are material-type and storage condition dependent.
      Therefore, the clinical selection of a glass-ionomer material should be based on
      the oral environment to which it will be subjected.

PMID- 17034015
TI  - Growing tissue-like constructs with Hep3B/HepG2 liver cells on PHBV microspheres
      of different sizes.
AB  - In this study, an oil-in-water emulsion solvent evaporation technique was used to
      fabricate poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV, 8% PHV),
      microspheres as scaffold, to guide liver cell growth. Human hepatoma cell lines,
      HepG2 and Hep3B, were cultured in vitro on both the microspheres and polymer
      films. SEM and optical microscope images showed that multilayer cells were formed
      among the microspheres to bridge them together and developed into cell-construct
      aggregates after 1 week of culture. MTT results showed that the cell
      proliferation on the microspheres was more than two times higher than that on the
      films after 12 days of culture. The cells seeded on microspheres secreted albumin
      2-4 times more than that on the positive control after 1 week of culture, which
      indicated that this hepatic function was greatly improved by the aggregation of
      cells on microspheres. Although HepG2 failed to express P-450 activity, this
      hepatic function was preserved when Hep3B cultured on microspheres. All the
      results indicated that PHBV microspheres are appropriate scaffolds for liver
      tissue engineering.

PMID- 17034016
TI  - Safety evaluation of large external fixation clamps and frames in a magnetic
      resonance environment.
AB  - Large orthopedic external fixation clamps and related components were evaluated
      for force, torque, and heating response when subjected to the strong
      electromagnetic fields of magnetic-resonance (MR) imaging devices. Forces induced
      by a 3-Tesla (T) MR scanner were compiled for newly designed nonmagnetic clamps
      and older clamps that contained ferromagnetic components. Heating trials were
      performed in a 1.5 and in a 3 T MR scanner with two assembled external fixation
      frames. Forces of the newly designed clamps were more than a factor 2 lower as
      the gravitational force on the device whereas, magnetic forces on the older
      devices showed over 10 times the force induced by earth acceleration of gravity.
      No torque effects could be found for the newly designed clamps. Temperature
      measurements at the tips of Schanz screws in the 1.5 T MR scanner showed a rise
      of 0.7 degrees C for a pelvic frame and of 2.1 degrees C for a diamond knee
      bridge frame when normalized to a specific absorption rate (SAR) of 2 W/kg. The
      normalized temperature increases in the 3 T MR scanner were 0.9 degrees C for the
      pelvic frame and 1.1 degrees C for the knee bridge frame. Large external fixation
      frames assembled with the newly designed clamps (390 Series Clamps), carbon fiber
      reinforced rods, and implant quality 316L stainless steel Schanz screws met
      prevailing force and torque limits when tested in a 3-T field, and demonstrated
      temperature increase that met IEC-60601 guidelines for extremities. The influence
      of frame-induced eddy currents on the risk of peripheral nerve stimulation was
      not investigated.

PMID- 17034017
TI  - Adolescent girls and criminal activity: role of MAOA-LPR genotype and
      psychosocial factors.
AB  - Recent findings among boys show that interactions between a polymorphism in the
      monoamine oxidase A gene promoter region (MAOA-LPR) and psychosocial factors
      predict criminal activity. The objective of this study was to investigate whether
      this finding could be extended to adolescent girls. One hundred nineteen female
      adolescents were recruited among respondents to a cross-sectional study of the
      total population of 16- and 19-year old girls. These girls constituted a randomly
      selected sub-sample from groups representing different degrees of risk behavior.
      The subjects filled in a questionnaire and were interviewed and genotyped with
      regard to MAOA-LPR. The results indicate that the long, (4-repeat) allele confer
      an increased risk for criminal behavior in the presence of psychosocial risk.
      Among girls without social risk, MAOA-LPR genotype was of no importance for
      criminal behavior. The present results suggest that previous observations on
      adolescent males, which demonstrate that the short MAOA-LPR genotype and
      psychosocial adversity interact to predict criminal activity, may not be
      applicable to females.

PMID- 17034018
TI  - Schizotypal dimensions: an intermediate phenotype associated with the COMT high
      activity allele.
AB  - BACKGROUND: Although catechol-O-methyltransferase (COMT) has long been suggested
      to be implicated in the pathogenesis of schizophrenia, association studies have
      generated discrepant results concerning the involvement of the COMT gene in
      schizophrenia. As several studies have suggested that schizotypal traits might be
      genetically related to schizophrenia, increased statistical power to detect gene
      effects could be obtained by using dimensional personality traits in unaffected
      relatives. METHODS: We tested the hypothesis that the functional Val158Met COMT
      polymorphism might contribute to the variance of self-reported schizotypal scores
      in a sample of 106 unaffected subjects, composed of controls (N = 57), first
      degree relatives of schizophrenic (N = 27) and of bipolar (N = 22) probands. We
      also looked for specific associations between COMT polymorphisms and the three
      dimensions of schizotypy (positive, negative, disorganized) assessed by the
      Schizotypal Personality Questionnaire (SPQ). RESULTS: We found that self-reported
      SPQ scores are related to COMT genotype (P = 0.01), with individuals homozygous
      for the high activity allele having the highest scores. This association is
      primarily due to specific associations with the positive (P = 0.001) and negative
      (P = 0.04) dimensions. CONCLUSIONS: Our data support the hypothesis that the
      functional COMT polymorphism could be involved in different psychotic dimensions.
      This confirms that studying specific schizotypal dimensions can help to identify
      the genes involved in the pathogenesis of psychosis.

PMID- 17034019
TI  - The Palau Early Psychosis Study: distribution of cases by level of genetic risk.
AB  - The Palau Early Psychosis Study (PEPS) was designed to examine the pathogenesis
      of early psychosis in a high-risk population isolate. This paper describes the
      characteristics of our community-based, non-help seeking sample of 404 Palauan
      adolescents and quantifies the presence of early psychosis by level of genetic
      risk. The sample included 53 offspring of a schizophrenic parent designated as
      "Genetically Highest Risk" (GHR+) and 68 nieces/nephews of sib-pairs/trios,
      designated as "Genetically High Risk" (GHR). The remaining subjects were
      recruited through a high school survey that identified 62 "Genetically Moderate
      Risk" (GMR) adolescents with an affected second or third degree relative and 221
      "Genetically Low Risk" (GLR) subjects with no close affected relatives. The GLR
      adolescents included 117 symptomatic or "Clinically High Risk" (CHR) adolescents
      and 104 asymptomatic normal controls. Based on a modified K-SADS-PL assessment,
      we identified 221 adolescents with early psychosis, 62 or 28% of whom had already
      transitioned to a psychotic disorder. Together, the two highest risk groups
      contributed 31% of the adolescent-onset psychosis cases and 27% of the
      prodromals. More than half of the early psychosis cases (53%) were GLR
      adolescents. The mean age of onset for DSM-IV psychosis was 12.9 years, and males
      transitioned at an earlier age than females. Our results indicate that Palauan
      adolescents, even GLR adolescents with no close affected relatives, have elevated
      rates of early psychosis. These young subjects can contribute valuable
      information about the familial transmission of schizophrenia, the developmental
      course of the illness, and rates of transition to frank psychosis.

PMID- 17034020
TI  - No association between ADRA2A polymorphisms and schizophrenia.
AB  - There is evidence to suggest that the alpha(2A)-adrenergic receptor may be
      involved in schizophrenia. With attention directed at the upstream regulatory
      region of the gene which codes for this receptor (ADRA2A), we proposed that
      single nucleotide polymorphisms (SNPs) within this region influences
      susceptibility to schizophrenia by altering the expression of this receptor. We
      opted to test for an influence on susceptibility by association study using 112
      schizophrenic/schizoaffective disorder patients and 159 controls. The region of
      interest was screened for SNPs using a combination of bioinformatic searches and
      sequencing. A total of nine SNPs were discovered, of which four (-5972-G/A, -2211
      A/T, -1291-C/G and -261-G/A) were genotyped in the entire clinical sample. No
      associations were evident, suggesting no influence for these SNPs in
      susceptibility to schizophrenia.

PMID- 17034021
TI  - Schizophrenic-like neurocognitive deficits in children and adolescents with 22q11
      deletion syndrome.
AB  - 22q11.2 Deletion Syndrome (22q11DS) is the most common genetic microdeletion
      syndrome affecting humans. The syndrome is associated with general cognitive
      impairments and specific deficits in visual-spatial ability, non-verbal
      reasoning, and planning skills. 22q11DS is also associated with behavioral and
      psychiatric abnormalities, including a markedly elevated risk for schizophrenia.
      Research findings indicate that people with schizophrenia, as well as those
      identified as schizoptypic, show specific cognitive deficits in the areas of
      sustained attention, executive functioning, and verbal working memory. The
      present study examined such schizophrenic-like cognitive deficits in children and
      adolescents with 22q11DS (n = 26) and controls (n = 25) using a cross-sectional
      design. As hypothesized, 22q11DS participants exhibited deficits in intelligence,
      achievement, sustained attention, executive functioning, and verbal working
      memory compared to controls. Furthermore, deficits in attention and executive
      functioning were more pronounced in the 22q11DS sample relative to general
      cognitive impairment. These findings suggest that the same pattern of
      neuropsychological impairment seen in patients with schizophrenia is present in
      non-psychotic children identified as at-risk for the development of schizophrenia
      based on a known genetic risk marker.

PMID- 17034022
TI  - Adjudicating neurocognitive endophenotypes for schizophrenia.
AB  - Although genetic influences on schizophrenia are well established, localization
      of the genes responsible for this illness has proven extremely difficult. Given
      evidence that genes predisposing to schizophrenia may be transmitted without
      expression of the clinical phenotype, efforts have focused on developing
      endophenotypes. While several neuropsychological measures have been proposed to
      be endophenotypes, few studies have systematically assessed batteries of
      neurocognitive tests to determine which tests are most sensitive to liability for
      the illness. Two hundred sixty-nine Latino individuals were administered a
      standard neuropsychological battery. Two hundred fourteen of these were members
      of families with at least two siblings diagnosed with schizophrenia or
      schizoaffective disorder. The remaining were community controls without history
      of major psychiatric illness. Neurocognitive measures found to be heritable were
      entered into analyses designed to determine which tests covary with the degree of
      genetic relationship to affected individuals. Although five measures were found
      to uniquely model genetic liability for schizophrenia, digit symbol coding was
      the most sensitive. To assess the specificity of these endophenotypes,
      performance on these measures were compared to family members with bipolar and
      unipolar affective disorders. These markers clearly distinguished between
      individuals with psychotic illnesses and those with major depression. As measures
      contributed uniquely to discriminate individuals at varying risk for
      schizophrenia, our findings imply multiple independently inherited elements to
      the liability for the illness. We present a practical model for adjudicating
      endophenotypes and determining which measures are best suited for use in linkage
      analyses.

PMID- 17034023
TI  - PTPN22 620W allele is not associated with aplastic anemia.
AB  - The 1858C/T variant in PTPN22 imparts a gain of function mutation dysregulating T
      cell stimulation and is associated with an array of autoimmune diseases. Using a
      case-control design, we compared the frequency of this polymorphism in 91
      patients with acquired aplastic anemia to 132 ethnically matched controls.
      Representation of the PTPN22 variant was not significantly different between the
      two populations, suggesting that this gene polymorphism does not contribute to
      the etiology of aplastic anemia. Aplastic anemia thus joins a list of autoimmune
      diseases that commonly lack a major humoral disease component and do not
      associate with the PTPN22 variant.

PMID- 17034024
TI  - Profound thrombocytopenia related to G-CSF.
AB  - Severe thrombocytopenia in association with G-CSF therapy is extremely rare. Here
      we report a case of profound thrombocytopenia in a 57-year-old male with
      refractory cardiac ischemia, who received G-CSF during an angiogenesis trial.
      After 5 days of G-CSF therapy (10 microg/kg/day) the platelet count fell
      progressively to a nadir of 5x10(9)/L. The patient received steroid,
      immunoglobulin and platelet support and recovered without sequelae. Subsequent
      investigations suggested an underlying immune-mediated thrombocytopenia, which we
      hypothesize was exacerbated by G-CSF therapy.

PMID- 17034025
TI  - Post-appendectomy thrombotic thrombocytopenic purpura: a case report and review
      of the literature.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by
      microangiopathic hemolytic anemia and thrombocytopenia with varying degrees of
      renal dysfunction, neurologic signs and symptoms, and fever. Evidence has
      supported that a large proportion of cases of acquired TTP are due to the
      accumulation of ultralarge von Willebrand factor (vWF) multimers due to an
      acquired deficiency in the vWF cleaving protease, ADAMTS-13. TTP is rare in the
      post-surgical setting but is best described after cardiothoracic and vascular
      surgeries. We present a case of postoperative TTP first presenting with
      microangiopathic hemolytic anemia and thrombocytopenia 9 days after emergent
      appendectomy for a ruptured appendix. ADAMTS-13 and factor H levels returned
      normal and an ADAMTS-13 inhibitor was not identified. To our knowledge, this is
      the first case report of postoperative TTP after an appendectomy and the first
      report with correlative ADAMTS-13 data. Plasma exchange with fresh frozen plasma
      followed by cryopoor plasma, along with steroids resulted in eventual remission
      of TTP in our patient. Early postoperative diagnosis and aggressive management
      with consideration of initiation of plasma exchange is imperative to decrease the
      morbidity and morality associated with TTP.

PMID- 17034026
TI  - Retrochorionic hematoma in congenital afibrinogenemia: resolution with fibrinogen
      concentrate infusions.
AB  - Without treatment, pregnancies in patients with congenital afibrinogenemia
      terminate in miscarriage at 5-6 weeks of gestation. Animal model studies have
      suggested that implantation site bleeding contributes to miscarriage in
      afibrinogenemia; however, retrochorionic hematoma in human congenital
      afibrinogenemia has not been previously observed. A patient with congenital
      afibrinogenemia receiving fibrinogen prophylaxis developed a retrochorionic
      hematoma in the first trimester. With continuous intensified fibrinogen
      concentrate replacement the hematoma resolved over 6 weeks, and the patient
      delivered a healthy infant. Median fibrinogen levels in the first trimester were
      48 mg/dL and in second and third trimester 44 mg/dL. Median fibrinogen levels
      under 60 mg/dL may be adequate to maintain pregnancy in patients with congenital
      afibrinogenemia, although it is possible that higher levels might reduce the risk
      of hemorrhagic events.

PMID- 17034027
TI  - Estimated glomerular filtration rate in sickle cell anemia is associated with
      polymorphisms of bone morphogenetic protein receptor 1B.
AB  - Renal disease is common in sickle cell anemia. In this exploratory work, we used
      data from a longitudinal study of the natural history of sickle cell disease to
      examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are
      associated with glomerular filtration rate (GFR). DNA samples and clinical and
      laboratory data were available for 1,140 patients with sickle cell anemia. GFR
      was estimated using the Cockcroft-Gault and Schwartz formulas for adults and
      children, respectively. We examined approximately 175 haplotype tagging (ht) SNPs
      in about 70 genes of the TGFbeta/BMP pathway for their association with GFR using
      linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP)
      receptor gene, yielded statistically significant associations (P values ranging
      from 0.015 to 0.046). Three haplotypes in this gene were also associated with
      GFR. The TGF-beta/BMP pathway has been associated with the development of
      diabetic nephropathy, which has some features in common with sickle cell
      nephropathy. Our results suggest that, as with other subphenotypes of sickle cell
      disease, renal function may be genetically modulated.

PMID- 17034028
TI  - Characterization of a novel deletion causing (deltabeta)0-thalassemia in a Thai
      family.
AB  - A novel deletion of the human beta-globin gene cluster associated with the
      increased level of fetal hemoglobin (Hb F) in adult life has been demonstrated in
      a Thai family. A Thai girl who was mistakenly diagnosed as beta-thalassemia/HbE
      is found to be the compound heterozygote of this mutation and Hb E. The
      heterozygous father had mild hypochromic and microcytic red blood cells and a
      high level of Hb F (23.2%). Polymorphic restriction sites in the beta-globin gene
      cluster identified the homozygous alleles, which localized the deletion region
      between the psibeta-globin and the 3' beta-globin genes. DNA polymerase that can
      amplify a long DNA template was employed to examine DNA fragment encompassing
      this deletion. A 11.3 kilobases (kb) of DNA deletion, beginning approximately 3.1
      kb 5' to the delta-globin gene and end in the intron 2 of the beta-globin gene
      was detected. DNA analysis revealed that this is a case of (deltabeta)(0)
      thalassemia with a novel mutation, which can lead to a mild form of beta
      thalassemia upon interaction with Hb E.

PMID- 17034029
TI  - Congenital amegakaryocytic thrombocytopenia--report of a new c-mpl gene missense
      mutation.
AB  - A 44-month old girl with congenital amegakaryocytic thrombocytopenia, already
      with pancytopenia, underwent an unrelated allogeneic cord blood transplantation
      with recovery of normal blood cell counts. The patient was a compound
      heterozygote for two c-mpl missense mutations inherited from both parents, one of
      them, a G578A exon 4 mutation leading to a cysteine to tyrosine replacement of
      codon 193, previously unreported.

PMID- 17034030
TI  - Management of cancer-associated thrombotic microangiopathy: what is the right
      approach?
AB  - A 49-year-old Caucasian woman presented with features suggestive of thrombotic
      microangiopathy (TMA). She did not respond to treatment with repeated plasma
      exchange and corticosteroids. A bone marrow biopsy revealed presence of
      metastatic carcinoma. A limited autopsy revealed presence of breast cancer with
      rib metastases. Though severe deficiency of von Willebrand factor-cleaving
      protease was initially proposed as a key pathogenetic factor for thrombotic
      thrombocytopenic purpura, subsequent studies involving patients with cancer
      associated TMA did not find as severe a deficiency of von Willebrand factor
      cleaving protease as is seen in idiopathic cases of thrombotic thrombocytopenic
      purpura. Here we address one approach of management of these patients with cancer
      associated TMA.

PMID- 17034031
TI  - Microrough titanium surface affects biologic response in MG63 osteoblast-like
      cells.
AB  - The purpose of this study was to define the surface properties of prepared
      titanium (Ti) disks, which served as a model system, and to contrast the biologic
      response of MG63 cells exposed to Ti disks with different levels of surface
      roughness. The surface properties interact with each other, resulting in a change
      of other surface qualities in addition to roughness due to the surface roughening
      procedure. The machined Ti disks were roughened by sandblasting and electric glow
      discharging. The surface properties of the Ti specimens were inspected through a
      comprehensive surface analysis. MG63 cell behaviors were compared along with cell
      number, alkaline phosphatase (ALP) activity, Runx2 gene expression, and type I
      collagen production. Statistics were evaluated, using analysis of variance
      (ANOVA). The sandblasted Ti disks demonstrated well-controlled surface roughness
      features and meaningful average roughness ranges, including the surface roughness
      of the "modern" microrough implant, used clinically. With increasing Ti surface
      roughness, the cell number decreased, while the ALP activity, type I collagen
      production, and Runx2 gene expression increased significantly. The rougher the Ti
      surface was, the sooner the Runx2 gene was expressed. Based on these results, we
      suggest that the microrough Ti surfaces of the 1-3 mum range may contribute
      effectively to osteogenic differentiation and proliferation in MG63 cells.

PMID- 17034032
TI  - Timing of radiation in children with medulloblastoma/PNET.
AB  - BACKGROUND: To evaluate the importance of timing of radiation therapy in children
      with PNET/medulloblastoma, treated at the Brazilian National Cancer Institute
      (INCA). PROCEDURE: The records of 101 children with confirmed diagnosis of
      medulloblastoma were retrospectively reviewed. Patients had a median follow-up of
      48 months (0.5-241 months). The age varied from 0.8 to 17.5 years (median: 7.6
      years) and 21.7% were 3 years old or younger. RESULTS: According to the data
      collected from patients that received treatment for medulloblastoma from 1983 to
      2001, the overall survival (OS) rate was 53% and the Disease Free Survival (DFS)
      rate was 40%. Multivariate analysis showed that under age 3 years, presence of
      neoplasic cells in the cerebrospinal fluid (CSF) at presentation or subtotal
      tumor resection resulted in a worse OS. The patients that received a biological
      effective dose (BED) greater than 44 Gy10 had better prognosis. Two-thirds of the
      patients had complete response after the initial treatment. Among them, 50% (34
      patients) recurred, and of those 34 patients, 42% of them (14 patients) had
      recurrence in the posterior fossa. CONCLUSION: Surgery with total resection of
      the tumor and absence of neoplasic cells in the CSF are effective predictors of
      better OS. Radiotherapy was more effective when a BED was greater than 44 Gy10.

PMID- 17034033
TI  - Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases
      the aggressiveness of prostate cancer cells.
AB  - BACKGROUND: Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key
      elements in the metastasis of prostate cancer cells to bone--but the mechanisms
      as to how it localizes to the marrow remains unclear. METHODS: Prostate cancer
      cell lines were stimulated with SDF-1 and evaluated for alterations in the
      expression of adhesion molecules using microarrays, FACs, and Western blotting to
      identify alpha(v)beta(3) receptors. Cell-cell adhesion and invasion assays were
      used to verify that activation of the receptor is responsive to SDF-1. RESULTS:
      We demonstrate that SDF-1 transiently regulates the number and affinity of
      alpha(v)beta(3) receptors by prostate cancer cells to enhance their metastatic
      behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased
      the expression of beta(3) receptor subunit and increased its phosphorylation in
      metastatic but not nonmetastatic cells. CONCLUSIONS: The transition from a
      locally invasive phenotype to a metastatic phenotype may be primed by the
      elevated expression of alpha(v)beta(3) receptors. Activation and increased
      expression of alpha(v)beta(3) within SDF-1-rich organs may participate in
      metastatic localization.

PMID- 17034034
TI  - Imaging brain activity during natural vision using CASL perfusion fMRI.
AB  - Functional MRI (fMRI) has begun to be used to explore human brain activity during
      ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI
      provides an appealing approach for imaging sustained brain activity during
      natural conditions because of its long-term temporal stability and ability to
      noninvasively quantify absolute cerebral blood flow (CBF). The present study used
      ASL perfusion fMRI to measure brain activation patterns associated with natural
      vision by concurrently recording CBF and blood oxygen level-dependent (BOLD)
      contrasts while subjects were freely viewing a cartoon movie. Reliable
      quantitative whole-brain CBF values ( approximately 60 mL/100g/min) as well as
      regional CBF values (45 approximately 80 mL/100g/min) were measured during movie
      viewing and resting states. The perfusion contrast revealed CBF increases in
      multiple visual pathway areas and frontal areas, and CBF decreases in
      ventromedial frontal cortex and superior temporal cortex during movie viewing
      compared to resting states. Concurrent BOLD contrast revealed similar but weaker
      activation and deactivation patterns. Regression analyses of both CBF data and
      BOLD data showed significant associations between activation in the middle
      temporal (MT) region and subjects' perception of motion. Region of interest
      analysis based on a priori literature-defined MT demonstrated significant
      monotonic stepwise associations between the intensity of motion perception and
      the CBF and BOLD signal changes. These results demonstrate the feasibility of
      using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural
      activation during natural and ecologically valid situations, and support the
      notion of maintained functional segregation and specialization during natural
      vision.

PMID- 17034035
TI  - Thermodynamic effects of proline introduction on protein stability.
AB  - The amino acid Pro is more rigid than other naturally occurring amino acids and,
      in proteins, lacks an amide hydrogen. To understand the structural and
      thermodynamic effects of Pro substitutions, it was introduced at 13 different
      positions in four different proteins, leucine-isoleucine-valine binding protein,
      maltose binding protein, ribose binding protein, and thioredoxin. Three of the
      maltose binding protein mutants were characterized by X-ray crystallography to
      confirm that no structural changes had occurred upon mutation. In the remaining
      cases, fluorescence and CD spectroscopy were used to show the absence of
      structural change. Stabilities of wild type and mutant proteins were
      characterized by chemical denaturation at neutral pH and by differential scanning
      calorimetry as a function of pH. The mutants did not show enhanced stability with
      respect to chemical denaturation at room temperature. However, 6 of the 13 single
      mutants showed a small but significant increase in the free energy of thermal
      unfolding in the range of 0.3-2.4 kcal/mol, 2 mutants showed no change, and 5
      were destabilized. In five of the six cases, the stabilization was because of
      reduced entropy of unfolding. However, the magnitude of the reduction in entropy
      of unfolding was typically several fold larger than the theoretical estimate of 
      4 cal K(-1) mol(-1) derived from the relative areas in the Ramachandran map
      accessible to Pro and Ala residues, respectively. Two double mutants were
      constructed. In both cases, the effects of the single mutations on the free
      energy of thermal unfolding were nonadditive.

PMID- 17034036
TI  - Complexity of free energy landscapes of peptides revealed by nonlinear principal
      component analysis.
AB  - Employing the recently developed hierarchical nonlinear principal component
      analysis (NLPCA) method of Saegusa et al. (Neurocomputing 2004;61:57-70 and IEICE
      Trans Inf Syst 2005;E88-D:2242-2248), the complexities of the free energy
      landscapes of several peptides, including triglycine, hexaalanine, and the C
      terminal beta-hairpin of protein G, were studied. First, the performance of this
      NLPCA method was compared with the standard linear principal component analysis
      (PCA). In particular, we compared two methods according to (1) the ability of the
      dimensionality reduction and (2) the efficient representation of peptide
      conformations in low-dimensional spaces spanned by the first few principal
      components. The study revealed that NLPCA reduces the dimensionality of the
      considered systems much better, than did PCA. For example, in order to get the
      similar error, which is due to representation of the original data of beta
      hairpin in low dimensional space, one needs 4 and 21 principal components of
      NLPCA and PCA, respectively. Second, by representing the free energy landscapes
      of the considered systems as a function of the first two principal components
      obtained from PCA, we obtained the relatively well-structured free energy
      landscapes. In contrast, the free energy landscapes of NLPCA are much more
      complicated, exhibiting many states which are hidden in the PCA maps, especially
      in the unfolded regions. Furthermore, the study also showed that many states in
      the PCA maps are mixed up by several peptide conformations, while those of the
      NLPCA maps are more pure. This finding suggests that the NLPCA should be used to
      capture the essential features of the systems.

PMID- 17034037
TI  - Stress urinary incontinence as the presenting symptom of primary male urethral
      diverticulum-A case report and literature review.
AB  - Primary male urethral diverticulum is quite uncommon. It is even more unusual for
      urinary incontinence to be a presenting symptom of primary male urethral
      diverticulum. Herein, we report on a 32-year-old male presenting with urine
      leakage on coughing or abdominal strain beginning from his early twenties. A
      congenital type bulbar urethral diverticulum is diagnosed by voiding
      cystourethrography and cystourethroscopy. Endoscopic unroofing of the
      diverticulum freed the patient from stress urinary incontinence after the
      surgery.

PMID- 17034038
TI  - Dynamics and assembly of the cytolethal distending toxin.
AB  - The cytolethal distending toxin (CDT) is a widespread bacterial toxin that
      consists of an active subunit CdtB with nuclease activity and two ricin-like
      lectin domains, CdtA and CdtC, that are involved in the delivery of CdtB into the
      host cell. The three subunits form a tripartite complex that is required to
      achieve the fully active holotoxin. In the present study we investigate the
      assembly and dynamic properties of the CDT holotoxin using molecular dynamics
      simulations and binding free energy calculations. The results have revealed that
      CdtB likely adopts a different conformation in the unbound state with a closed
      DNA binding site. The two characterized structural elements of the aromatic patch
      and groove on the CdtA and CdtC protein surfaces exhibit high mobility, and free
      energy calculations show that the heterodimeric complex CdtA-CdtC, as well as the
      CdtA-CdtB and CdtB-CdtC sub-complexes are less energetically stable as compared
      to the binding in the tripartite complex. Analysis of the dynamical cross
      correlation map reveals information on the correlated motions and long-range
      interplay among the CDT subunits associated with complex formation. Finally, the
      estimated binding free energies of subunit interactions are presented, together
      with the free energy decomposition to determine the contributions of residues for
      both binding partners, providing insight into the protein-protein interactions in
      the CDT holotoxin.

PMID- 17034039
TI  - Needle electromyography of the rectus abdominis in patients with amyotrophic
      lateral sclerosis.
AB  - We examined the role of needle electromyography (EMG) of the rectus abdominis
      (RA) in assessing thoracic involvement in amyotrophic lateral sclerosis (ALS).
      Needle EMG of the RA was performed in 67 patients with sporadic ALS and 110
      healthy controls. The presence of abnormal spontaneous activity, configuration of
      motor unit action potentials (MUAPs), and recruitment pattern of motor unit
      potentials were examined. In ALS patients, MUAPs in the RA were of prolonged
      duration, large amplitude, and showed increased prevalence of polyphasic
      waveforms compared to controls. Significant differences in MUAP parameters,
      presence of abnormal spontaneous potentials, and interference patterns were noted
      between ALS patients and controls. Additionally, we found that active denervation
      was more frequent in the RA of ALS patients with dyspnea than those without
      dyspnea. Thus, conventional needle EMG of the RA is a valuable
      electrophysiological method to assess clinical and subclinical involvement of
      thoracic lower motor neurons in patients with suspected ALS.

PMID- 17034040
TI  - Electrical stimulation based on chronaxie reduces atrogin-1 and myoD gene
      expressions in denervated rat muscle.
AB  - Denervation induces muscle fiber atrophy and changes in the gene expression rates
      of skeletal muscle. Electrical stimulation (ES) is a procedure generally used to
      treat denervated muscles in humans. This study evaluated the effect of ES based
      on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in
      denervated tibialis anterior (TA) muscle of Wistar rats. Five groups were
      examined: (1) denervated (D); (2) D+ES; (3) sham denervation; (4) normal (N); and
      (5) N+ES. Twenty muscle contractions were stimulated every 48 h using surface
      electrodes. After 28 days, ES significantly decreased the expression of myoD and
      atrogin-1 in D+ES compared to the D group. However, ES did not prevent muscle
      fiber atrophy after denervation. Thus, ES based on chronaxie values and applied
      to denervated muscles using surface electrodes, as normally used in human
      rehabilitation, was able to reduce the myoD and atrogin-1 gene expressions, which
      are related to muscular growth and atrophy, respectively. The results of this
      study provide new information for the treatment of denervated skeletal muscle
      using surface ES.

PMID- 17034041
TI  - Ligand-supported homology modeling of the human angiotensin II type 1 (AT(1))
      receptor: insights into the molecular determinants of telmisartan binding.
AB  - Angiotensin II type 1 (AT(1)) receptor belongs to the super-family of G-protein
      coupled receptors, and antagonists of the AT(1) receptor are effectively used in
      the treatment of hypertension. To understand the molecular interactions of these
      antagonists, such as losartan and telmisartan, with the AT(1) receptor, a
      homology model of the human AT(1) (hAT(1)) receptor with all connecting loops was
      constructed from the 2.6 A resolution crystal structure (PDB i.d., 1L9H) of
      bovine rhodopsin. The initial model generated by MODELLER was subjected to a
      stepwise ligand-supported model refinement. This protocol involved initial
      docking of non-peptide AT(1) antagonists in the putative binding site, followed
      by several rounds of iterative energy minimizations and molecular dynamics
      simulations. The final model was validated based on its correlation with several
      structure-activity relationships and site-directed mutagenesis data. The final
      model was also found to be in agreement with a previously reported AT(1)
      antagonist pharmacophore model. Docking studies were performed for a series of
      non-peptide AT(1) receptor antagonists in the active site of the final hAT(1)
      receptor model. The docking was able to identify key molecular interactions for
      all the AT(1) antagonists studied. Reasonable correlation was observed between
      the interaction energy values and the corresponding binding affinities of these
      ligands, providing further validation for the model. In addition, an extensive
      unrestrained molecular dynamics simulation showed that the docking-derived bound
      pose of telmisartan is energetically stable. Knowledge gained from the present
      studies can be used in structure-based drug design for developing novel ligands
      for the AT(1) receptor.

PMID- 17034042
TI  - Osteoactivin acts as downstream mediator of BMP-2 effects on osteoblast function.
AB  - Our laboratory previously showed that osteoactivin (OA) is a novel, osteoblast
      related glycoprotein that plays a role in osteoblast differentiation and
      function. The purpose of this study was to examine the regulation of OA
      expression by BMP-2 and the role OA plays as a downstream mediator of BMP-2
      effects in osteoblast function. Using primary osteoblast cultures, we tested
      different doses of BMP-2 on the regulation of OA expression during osteoblast
      development. To test whether Smad-1 signaling is responsible for BMP-2 regulation
      of OA expression, osteoblast cultures were transfected with Smad1 siRNA, treated
      with 50 ng/ml of BMP-2 and analyzed by Western blot. BMP-2 treatment increased OA
      mRNA and protein expression in a dose-dependent manner and this upregulation was
      blocked in Smad1 siRNA transfected cultures. We next examined whether the role of
      OA as a downstream mediator of BMP-2 effects on osteoblast differentiation and
      matrix mineralization. Osteoblast cultures were transfected with OA antisense
      oligonucleotides and treated with 50 ng/ml of BMP-2. Cultures transfected with OA
      antisense oligonucleotides and treated with BMP-2 showed a reduction of OA
      expression associated with a significant reduction in early and late
      differentiation markers induced by BMP-2. Therefore, OA acts, at least in part,
      as a downstream mediator of BMP-2 effects on osteoblast differentiation and
      matrix mineralization. Our findings suggest that BMP-2 regulates OA expression
      through the Smad1 signaling pathway. Our data also emphasize that OA protein acts
      as a downstream mediator of BMP-2 effects on osteoblast differentiation and
      function.

PMID- 17034043
TI  - Identification of OORP-T, a novel oocyte-specific gene encoding a protein with a
      conserved oxysterol binding protein domain in rainbow trout.
AB  - Genes specifically expressed in oocytes are important for the development of
      oocytes and early embryos. By analyzing expressed sequence tags (ESTs) from a
      rainbow trout oocyte cDNA library, we identified a novel EST sequence that does
      not show homology to any sequences in the GenBank. Analysis of tissue
      distribution by RT-PCR revealed that this gene was only expressed in unfertilized
      oocytes. Sequencing of the EST clone identified a cDNA of 3,163 bp. Northern blot
      analysis showed the novel gene has a single transcript of 3.4 kb. Additional 5'
      sequence was obtained by 5' RACE, extending the novel cDNA to 3,333 bp. Analysis
      of the full-length cDNA identified an open reading frame (ORF) encoding a protein
      of 564 amino acids. The novel protein contains a conserved oxysterol binding
      protein (OSBP) domain at the C terminus that is characteristic of OSBP-related
      proteins (ORPs) implicated in lipid metabolism. Therefore, we named the novel
      gene as Oocyte-specific Oxysterol binding protein Related-Protein of Trout (OORP
      T). In situ hybridization showed that the OORP-T mRNA appears to be confined to
      the cytoplasm of vitellogenic oocytes. Transcription of OORP-T appears to start
      during pre-vitellogenesis and increases steadily, reaching its peak in the late
      vitellogenic stage. OORP-T transcript is abundantly present in unfertilized eggs
      but the level drops significantly in day 2 embryos and continues to decline in
      day 7 embryos after which it remains low. We propose that OORP-T may play an
      important role in the utilization of yolk-derived lipid products during oocyte
      development and early stages of embryonic development in rainbow trout.

PMID- 17034044
TI  - Interspecies nuclear transfer of Tibetan antelope using caprine oocyte as
      recipient.
AB  - Interspecies nuclear transfer is an invalulable tool for studying nucleus
      cytoplasm interactions; and at the same time, it provides a possible alternative
      to clone endangered animals whose oocytes are difficult to obtain. In the present
      study, we investigated the possibility of cloning Tibetan antelope embryos using
      abattoir-derived caprine oocytes as recipients. Effects of culture conditions,
      enucleation timing, and donor cell passages on the in vitro development of
      Tibetan antelope-goat cloned embryos were studied. Maternal to zygotic transition
      timing of interspecies Tibetan antelope embryos was also investigated using two
      types of cloned embryos, Tibetan antelope-rabbit and Tibetan antelope-goat
      embryos. Our results indicate that: (1) goat oocyte is able to reprogram somatic
      cells of different genus and supports development to blastocyst in vitro. (2)
      Coculture system supported the development of Tibetan antelope-goat embryos to
      blastocyst rate stage (4.0%), while CR1aa alone did not. (3) When MII phase
      enucleated caprine cytoplast and TII phase enucleated caprine cytoplast were used
      as recipients, the fusion rate and blastocyst rate of hybrid embryos were not
      statistically different (73.9% vs. 67.4%; 4.0% vs. 1.1%). (4) When donor cells at
      3-8 passages were used, 2.9% hybrid embryos developed to blastocysts, while none
      developed to blastocysts when cells at 10-17 passages were used. (5) There may be
      a morula-to-blastocyst block for Tibetan antelope-goat, while there may be an 8-
      to 16-cell block for Tibetan antelope-rabbit embryos.

PMID- 17034045
TI  - Improved beta-protein structure prediction by multilevel optimization of nonlocal
      strand pairings and local backbone conformation.
AB  - Proteins with complex, nonlocal beta-sheets are challenging for de novo structure
      prediction, due in part to the difficulty of efficiently sampling long-range
      strand pairings. We present a new, multilevel approach to beta-sheet structure
      prediction that circumvents this difficulty by reformulating structure generation
      in terms of a folding tree. Nonlocal connections in this tree allow us to
      explicitly sample alternative beta-strand pairings while simultaneously exploring
      local conformational space using backbone torsion-space moves. An iterative,
      energy-biased resampling strategy is used to explore the space of beta-strand
      pairings; we expect that such a strategy will be generally useful for searching
      large conformational spaces with a high degree of combinatorial complexity.

PMID- 17034046
TI  - Serial nuclear transfer improves the developmental potential of mouse embryos
      cloned from oocytes matured in a protein-free medium.
AB  - Germinal vesicle (GV) oocytes matured in vitro are an alternative source for
      cytoplasmic recipients of nuclear transfer (NT). However, the developmental
      potential of oocytes matured in vitro is limited. In this study, we developed a
      protein-free maturation medium for mouse GV oocytes. Following parthenogenetic
      activation, the oocytes matured in the protein-free medium develop to blastocyst
      stage with a high efficiency, even up to the rate obtained from in vivo MII
      oocytes (90.6% vs. 92.8%). Using the oocytes matured in the protein-free medium
      as the recipient, NT embryos develop to the blastocyst stage (17.6%). To further
      improve the developmental potential of NT embryos, we performed serial NT and
      compared the effect of three different activated cytoplasm samples derived from
      in vitro matured oocytes as the second recipient, that is, the effect of in vitro
      fertilized (IVF) zygote, the preactivated cytoplast and the IVF cytoplast, on the
      development of NT embryos. We found that when the pronucleus of NT zygote was
      transferred into the cytoplasm of the IVF zygote, the blastocyst formation
      increased to 39.4%. This is the first report to demonstrate the IVF zygote from
      oocytes matured in protein-free medium can be used successfully as the recipient
      for serial NT to enhance the developmental potential of mouse NT embryos from
      oocytes matured in the protein-free medium.

PMID- 17034047
TI  - Digital image analysis of the flagellar beat of activated and hyperactivated
      suncus spermatozoa.
AB  - The flagellar beat of hyperactivated Suncus spermatozoa was analyzed by digital
      imaging and was compared to that of the nonhyperactivated (activated) spermatozoa
      in order to examine the function of the accessory fibers during the flagellar
      beat and the sliding filament mechanism inducing the motility of the
      hyperactivated spermatozoa. Unusual large and long characteristics of the
      accessory fibers were involved in generating the gently curved bends and a low
      beat frequency. Examination of the motility parameters of the flagellar beat of
      the activated and hyperactivated spermatozoa attached to a slide glass by their
      heads revealed that there were two beating modes: a frequency-curvature dependent
      mode in the activated flagellar beat and a nearly constant frequency mode in the
      hyperactivated flagellar beat. The hyperactivated flagellar beat was
      characterized by sharp bends in the proximal midpiece and a low beat frequency.
      The sharp bends in the proximal midpiece were induced by the increase in the
      total length of the microtubule sliding at the flagellar base. The rate of
      microtubule sliding (sliding velocity) in the axoneme remained almost constant in
      the flagellar beat of both the activated and hyperactivated spermatozoa.
      Comparison of the sliding velocity in Suncus, golden hamster, monkey, and sea
      urchin sperm flagella with their stiffness suggests that the sliding velocity is
      determined by the stiffness at the flagellar base and that the same sliding
      microtubule system functions in both mammalian and echinoderm spermatozoa.

PMID- 17034048
TI  - Meiotic competence and acetylation pattern of UV light classified mouse antral
      oocytes after meiotic arrest with isobutylmethylxanthine.
AB  - Chromatin transformation from a diffused or NSN configuration to a compacted or
      SN shape that forms a ring around the nucleolus is regarded as one of the
      modifications necessary for successful embryonic development. But the process of
      the transformation is poorly understood. In this study we cultured mouse antral
      oocytes under meiotic arrest with IBMX for periods between 3 and 24 hr. We
      observed the chromatin status of the oocytes before and after culture under UV
      illumination. We reported here that the NSN configured oocytes transformed
      temporally through an intermediate form into the SN configuration while under
      meiotic arrest in vitro. Meiotic rate was improved in the NSN oocytes after the
      meiotic arrest but decreased in the SN oocytes. We also reported that chromatin
      of both the NSN and SN oocytes was acetylated and the two groups underwent the
      same pattern of H4/K5 deacetylation during meiotic maturation. We hypothesized
      that the transformation of mouse oocyte from the NSN to SN type may be time
      rather than oocyte size specific and the abrupt deacetylation of NSN oocyte
      during spontaneous maturation may explain its poor meiotic and developmental
      competence.

PMID- 17034049
TI  - Glycoproteins of the vitelline envelope of Amphibian oocyte: biological and
      molecular characterization of ZPC component (gp41) in Bufo arenarum.
AB  - The vitelline envelope (VE) participates in sperm-egg interactions during the
      first steps of fertilization. In Bufo arenarum, this envelope is composed of at
      least four glycoproteins, with molecular masses of 120, 75, 41, and 38 kDa and
      molar ratio of 1:1.3:7.4:4.8, respectively. These components were isolated and
      covalently coupled to silanized glass slides in order to study their sperm
      binding capacity. When considering the molar ratio of the glycoproteins in the
      egg-envelope and assuming that each protein is monovalent for sperm, the assay
      showed that gp41 and gp38 possess 55 and 25% of total sperm-binding activity. We
      obtained a full-length cDNA of gp41 (ZPC), comprising a sequence for 486 amino
      acids, with 43.3% homology with Xenopus laevis ZPC. As in the case of mammalian
      ZP3 and Xenopus ZPC, Bufo ZPC presented a furin-like (convertase) and a C
      terminal transmembrane domain (TMD) reflecting common biosynthetic and secretory
      pathways. As it was reported for some fishes, we obtained evidence that suggests
      the presence of more than one zpc gene in Bufo genome, based on different partial
      cDNA sequences of zpc, Southern blots and two-dimensional SDS-PAGE of
      deglycosylated egg-envelope components. As far as we are aware, this is the first
      observation of the presence of different zpc genes in an Amphibian species.

PMID- 17034050
TI  - Heat stress-induced apoptosis in porcine in vitro fertilized and parthenogenetic
      preimplantation-stage embryos.
AB  - Decades worth of research have consistently shown the adverse effects of elevated
      temperatures on reproductive parameters of livestock species. The objective of
      this study was to evaluate the developmental and apoptotic responses of porcine
      in vitro fertilized (IVF) and parthenogenetically activated (PA) embryos heat
      stressed at the late 1-cell stage. Embryos were heat stressed (HS) at 42 degrees
      C for 9 hr starting 22 hr after insemination or artificial activation stimulus.
      Non heat-stressed (NHS) control embryos were maintained at 39 degrees C for the
      duration of the experiments. TUNEL staining on Day 5 of development demonstrated
      that heat stress elicited a significant apoptotic response in IVF embryos (45.6%
      of HS embryos and 26.7% of NHS embryos were apoptotic; P<0.05), but not in PA
      embryos (51.1% and 39.9% for HS and NHS embryos, respectively; P>0.1). And, while
      IVF embryos were highly susceptible to heat-induced developmental perturbations
      (20.6% and 8.8% development to blastocyst for NHS and HS embryos, respectively;
      P<0.05), elevated temperatures did not affect blastocyst rates in PA embryos
      (22.2% for NHS PA embryos and 21.2% for HS PA embryos; P>0.1). These findings
      indicate that, as in other systems studied, IVF pig embryos are directly affected
      adversely by heat stress conditions. Parthenogenetic embryos, though, appear to
      be surprisingly tolerant of the elevated temperatures. The differences between
      IVF and PA embryos in their response to heat stress warrants further
      investigation.

PMID- 17034051
TI  - Estimation of melting points of organic compounds-II.
AB  - A model for calculation of melting points of organic compounds from structure is
      described. The model utilizes additive, constitutive and nonadditive,
      constitutive molecular properties to calculate the enthalpy of melting and the
      entropy of melting, respectively. Application of the model to over 2200
      compounds, including a number of drugs with complex structures, gives an average
      absolute error of 30.1 degrees.

PMID- 17034052
TI  - Release of gentamicin from a tricalcium phosphate bone implant.
AB  - The impregnation and elution of gentamicin antibiotic from a commercially
      available porous beta-tricalcium phosphate (TCP) bone implant material (Vitoss,
      Orthovita, Inc.) was investigated in vitro. Sustained local antibiotic release is
      an attractive method for the prevention of infection following surgery. The
      purpose of this study was to evaluate the use of the naturally forming clot that
      occurs within a porous tissue scaffold when combined with autologous blood or
      bone marrow aspirate (BMA) as a method for achieving controlled drug delivery.
      The diffusion of antibiotic from porous TCP scaffolds was studied using water,
      clotted blood, or BMA as impregnating fluids. Incorporation of the drug into the
      porous scaffold using clotted blood or BMA as a binder produced slowed release
      relative to aqueous impregnated and dried samples. Modifications were made to the
      elution method to simulate restricted diffusion due to surrounding clotted blood,
      tissue, or bone that would occur in vivo. These modified methods simulated
      release in a surgical site and showed long release profiles, with significant
      amounts of antibiotic being released for up to 2 weeks. We concluded that adding
      gentamicin with autologous BMA is a promising method of controlling drug release.

PMID- 17034053
TI  - Novel epididymis-specific mRNAs downregulated by HE6/Gpr64 receptor gene
      disruption.
AB  - Targeted disruption of the epididymis-specific HE6/Gpr64 receptor gene in mice
      led to male infertility. In order to characterize the phenotype at a molecular
      level, we compared the gene expression patterns of wild type (wt) versus knockout
      (KO) caput epididymides. The caput region of KO males, although morphologically
      normal, nevertheless showed an aberrant expression pattern. Combining micro array
      analysis, differential library screening, Northern blot analysis and quantitative
      RT-PCR, we found that the knockout of the HE6/Gpr64 receptor was mainly
      associated with the downregulation of genes specific to the initial segment. The
      list of KO downregulated transcripts comprised Enpp2/autotaxin, the lipocalins 8
      and 9, the beta-defensin Defb42, cystatins 8 and 12, as well as the membrane
      proteins Adam (A Disintegrin And Metalloprotease) 28, claudin-10, EAAC1, and the
      novel Me9. Clusterin/ApoJ and osteopontin/Spp1 mRNAs, on the other hand, were
      upregulated in the KO tissues. The Me9 transcript was studied in further detail,
      and we report here a cluster of related epididymis-specific genes. Me9 is
      specifically expressed in the initial segment and is representative of a novel
      and highly conserved mammalian gene family. The family consists of single-exon
      genes only; intron-containing paralogs have not yet been ascertained. The cloned
      cDNA sequences predicted hydrophobic polytopic membrane proteins containing the
      DUF716 motif. Protein expression was shown in the rodent caput epididymidis but
      remained uncertain in primates.

PMID- 17034054
TI  - Isolation and characterization of embryonic stem cell-like cells from in vitro
      produced buffalo (Bubalus bubalis) embryos.
AB  - This study was carried out to isolate and characterize buffalo embryonic stem
      (ES) cell-like cells from in vitro-produced embryos. Inner cell mass (ICM) cells
      were isolated either mechanically or by enzymatic digestion from 120 blastocysts
      whereas 28 morulae were used for the isolation of blastomeres mechanically. The
      ICM cells/ blastomeres were cultured on mitomycin-C-treated feeder layer. Primary
      cell colony formation was higher (P < 0.05) for hatched blastocysts (73.1%,
      30/41) than that for early/expanded blastocysts (25.3%, 20/79). However, no
      primary cell colonies were formed when blastomeres obtained from morulae were
      cultured. Primary colonies were formed in 14.1% (12/85) of intact blastocyst
      culture, which was significantly lower (P < 0.05) than that of 41.6% for ICM
      culture. These colonies were separated by enzymatic or mechanical disaggregation.
      Using mechanical disaggregation method, the cells remained undifferentiated and
      two buffalo ES cell-like cell lines (bES1, bES2) continued to grow in culture up
      to eight passages. However, disassociation through enzymatic method resulted in
      differentiation. Undifferentiated cells exhibited stem cell morphological
      features, normal chromosomal morphology, and expressed specific markers such as
      alkaline phosphatase (AP) and Oct-4. Cells formed embryoid bodies (EBs) in
      suspension culture; extended culture of EBs resulted in formation of cystic EBs.
      Following prolonged in vitro culture, these cells differentiated into several
      types of cells including neuron-like and epithelium-like cells. Furthermore, the
      vitrified-thawed ES cell-like cells also exhibited typical stem cell
      characteristics. In conclusion, buffalo ES cell-like cells could be isolated from
      in vitro-produced blastocysts and maintained in vitro for prolonged periods of
      time.

PMID- 17034055
TI  - Supracondylar process with a high origin of the radial artery.

PMID- 17034056
TI  - C3, C4, C5, keep you alive, or do they?

PMID- 17034057
TI  - The iliacus minimus muscle.

PMID- 17034058
TI  - Caroticoclinoid foramen with interclinoid osseous bar.

PMID- 17034059
TI  - Bilateral lateral bipartite levator palpebrae superioris muscles.

PMID- 17034060
TI  - The association between birth season and future development of childhood asthma.
AB  - The aim of this study was to examine a possible association between birth season
      (date of birth) and future development of asthma in children. A case-control
      study was designed to include asthmatic children aged 2-7 years, living in the
      city of Beer-Sheva, in southern Israel, registered in one pediatric center.
      Controls were healthy children matched for age and registered at the same clinic.
      Demographic data, past medical history, and asthma history and severity were
      collected using the computerized medical charts and asthma registry. A structured
      telephone questionnaire was used to complete the data. Children with a history of
      prematurity or chronic significant illness were excluded from the study. Sixty
      six children and 69 controls were enrolled in the study. There were significantly
      more males in the asthmatic group compared to controls (P = 0.003). History of
      bronchiolitis or recurrent wheezing episodes in the first year, family history of
      asthma, and Middle-Eastern origin were significantly more common among asthmatic
      children than controls (P < 0.001). Asthmatic children were more likely to be
      born between March and June and least likely to be born between October and
      December, compared to controls (P < 0.05). Multivariate logistic regression
      analysis revealed three variables to be independent significant risk factors for
      development of asthma: birth season between March and June, acute bronchiolitis
      or recurrent wheezing episodes during first year of life, and male gender. Birth
      season during late winter and spring is associated with asthma during childhood.

PMID- 17034061
TI  - Insulin and obstructive sleep apnea in obese Chinese children.
AB  - OBJECTIVE: In adults, obstructive sleep apnea (OSA) is associated with insulin
      resistance and dyslipidemia. We aimed to establish correlation between OSA, serum
      lipid profile, and insulin levels in obese snoring children. METHODS: Consecutive
      obese children with habitual snoring were recruited. They underwent physical
      examination, overnight polysomnography (PSG), and metabolic studies. OSA was
      diagnosed if apnea hypopnea index (AHI) > 1.0, and cases were considered to have
      moderate to severe OSA if AHI > 10. RESULTS: Ninety-four obese subjects with
      habitual snoring were studied. Seventy-three subjects were male and the median
      age of the studied group was 12.0 years (IQR 9.7-13.9). None of the subjects had
      active cardiopulmonary disease, and the BMI values of our subjects were >95th
      percentile using local reference charts. Sixty subjects had OSA, 47 being mild,
      and 13 being moderate to severe OSA. Multiple logistic regression analysis
      revealed that saturation nadir and insulin levels were significantly associated
      with OSA. CONCLUSION: OSA is prevalent among obese children with habitual snoring
      and insulin is independently associated with the condition. Its role in the
      cardiovascular complications of childhood sleep apnea is worthy of further
      exploration.

PMID- 17034063
TI  - Outcome in the real-world of coronary high-risk intervention with drug-eluting
      stents (ORCHID) -- a single-center study comparing Cypher sirolimus-eluting with
      Taxus paclitaxel-eluting stents.
AB  - OBJECTIVE: We present real world experience from a single center registry
      comparing the 6-month outcome of percutaneous coronary intervention (PCI) in
      unselected high-risk individuals using either sirolimus-eluting (SES) or
      paclitaxel-eluting stents (PES). METHODS/RESULTS: We compared clinical outcome at
      6 months follow-up in two cohorts of 156 consecutive patients (total n = 312) who
      underwent SES (June 2002-February 2003) and PES (march 2003-July 2003)
      implantation. The primary endpoint was a composite of major adverse cardiac
      events (MACE). Baseline clinical characteristics were well matched. The 6-month
      target vessel revascularization (TVR) rates were 1.9% (SES) and 2.6% (PES) and
      MACE rates were similar in the two groups (SES 4.5% vs. PES 3.2%, P = NS). In the
      PES group, intervention for multivessel disease, bifurcation lesions and in small
      vessels was more common, and for in-stent restenosis less common, reflecting the
      impact of drug eluting stents on indications for PCI. The incidence of sub-acute
      stent thrombosis, related to inadequate antiplatelet therapy in 3 of the 6 cases,
      was 0.95% with no difference between the two groups. CONCLUSION: This study
      confirms the safety and efficacy of SES and PES in unselected high risk patients
      undergoing PCI. Clinical outcomes of both stents are equivalent at 6 months with
      low rates of MACE and TVR. These data provide important complementary information
      to forthcoming randomized studies.

PMID- 17034065
TI  - Survivin expression levels as independent predictors of survival for osteosarcoma
      patients.
AB  - Survivin expression has been detected in various cancers and correlations have
      been recognized between the level of expression of this gene in tumors and
      prognosis. However, the aforementioned authors did not evaluate correlations
      between prognosis and survivin expression levels using surgically resected
      samples. In this study, we retrospectively investigated outcomes by examining the
      correlations between expression of this gene and clinicopathological parameters.
      Biopsy and resected specimens from which paraffin-embedded tissues could be
      extracted, were available from 16 patients in our hospital. We used the RT-PCR
      method and conducted a densitometric analysis to determine the ratio of survivin
      relative to h-GAPDH as an internal marker. Expression of survivin mRNA was
      detected in all samples. There was a significant negative correlation between
      survivin expression levels and duration of follow up, in months, using the
      Spearman's rank for the initial biopsy samples (rho=-0.775, p<0.01) and those
      obtained after chemotherapy (rho=-0.687, p<0.01). Moreover, Cox multivariate
      regression identified the survivin expression levels in both biopsy and post
      chemotherapy samples as independent predictors of survival. We conclude that
      survivin levels in both initial biopsy and post-chemotherapy samples are useful
      prognostic indicators.

PMID- 17034064
TI  - Efficacy of intracoronary nicardipine in the treatment of no-reflow during
      percutaneous coronary intervention.
AB  - OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of
      nicardipine in reversing no-reflow during percutaneous coronary intervention
      (PCI). BACKGROUND: No-reflow is a common complication of PCI in patients with
      acute coronary syndromes or venous bypass graft disease. Although nicardipine has
      an attractive pharmacological profile and has been used clinically to treat no
      reflow, there is a paucity of published data regarding its effectiveness in this
      setting. METHODS: We conducted a retrospective analysis of 72 consecutive
      patients who received intracoronary nicardipine to reverse no-reflow during
      coronary intervention. Qualitative TIMI flow grade and quantitative TIMI frame
      count methods were used to assess the efficacy of nicardipine. RESULTS: A mean of
      460 +/- 360 mcg of intracoronary nicardipine was used. No-reflow was successfully
      reversed with complete restoration of TIMI 3 flow in 71 of 72 patients (98.6%).
      TIMI flow grade improved from 1.65 +/- 0.53 prior to nicardipine to 2.97 +/- 0.24
      after treatment (P < 0.001). TIMI frame count decreased from 57 +/- 40 at the
      time of no-reflow to 15 +/- 12 after nicardipine administration (P < 0.001).
      Nicardipine therapy was well tolerated without adverse hemodynamic or
      chronotropic effects. CONCLUSIONS: In this largest series to date, intracoronary
      nicardipine was demonstrated to be a safe and highly effective pharmacological
      agent to reverse no-reflow during PCI.

PMID- 17034066
TI  - Proceedings of the 2nd International Workshop on Vaccine Adjuvants and
      Glycoconjugates, Varadero, Cuba, 11-15 April 2004.

PMID- 17034067
TI  - Influences on advancement of nursing knowledge.

PMID- 17034068
TI  - Nursing and medicine: continuing challenges.

PMID- 17034069
TI  - Evaluation of diagnostic tests for infectious diseases: general principles.

PMID- 17034070
TI  - Evaluation of rapid diagnostic tests: malaria.

PMID- 17034071
TI  - The dialogue within nursing theory-guided practice: a frontier of knowledge and
      development.

PMID- 17034072
TI  - Readers' responses and author's reply to "cultural awareness: a prescription for
      more effective medicine".

PMID- 17034073
TI  - Centres of excellence in cardiology: the Hammersmith Hospital.

PMID- 17034074
TI  - Commentary: vitamin A supplementation for reducing the risk of mother-to-child
      transmission of HIV infection.

PMID- 17034075
TI  - Commentary: vitamin A supplementation for reducing the risk of mother-to-child
      transmission of HIV infection.

PMID- 17034076
TI  - Mensuration, Mendel, and a 19th century public health justification for US
      imperialism.

PMID- 17034077
TI  - Legacy: inside the Chernobyl exclusion zone.

PMID- 17034078
TI  - Visualization of localized intense optical fields in single gold-nanoparticle
      assemblies and ultrasensitive Raman active sites.
AB  - We demonstrate visualization of localized intense electromagnetic fields in real
      space in well-tailored dimeric and trimeric gold nanospheres by using near-field
      optical techniques. With two-photon induced luminescence and Raman measurements,
      we show that the electric field is confined at an interstitial site in the
      aggregate. We also demonstrate optical switching operations for the electric
      field localized sites in the trimer structure.

PMID- 17034079
TI  - Biotemplated nanopatterning of planar surfaces with molecular motors.
AB  - We report on the generation of nanometer-wide, non-topographical patterns of
      proteins on planar surfaces. In particular, we used the regular lattice of
      reconstituted microtubules as template structures to specifically bind and
      transfer kinesin-1 and nonclaret disjunctional motor proteins. The generated
      tracks, which comprise dense and structurally oriented arrays of functional motor
      proteins, proved to be highly efficient for the guiding of microtubule
      transporters.

PMID- 17034080
TI  - Electron transfer dynamics of bistable single-molecule junctions.
AB  - We present transport measurements of single-molecule junctions bridged by a
      molecule with three benzene rings connected by two double bonds and with thiol
      end-groups that allow chemical binding to gold electrodes. The I-V curves show
      switching behavior between two distinct states. By statistical analysis of the
      switching events, we show that a 300 meV mode mediates the transition between the
      two states. We propose that breaking and reformation of a S-H bond in the contact
      zone between molecule and electrode explains the observed bistability.

PMID- 17034081
TI  - Impact ionization can explain carrier multiplication in PbSe quantum dots.
AB  - The efficiency of conventional solar cells is limited because the excess energy
      of absorbed photons converts to heat instead of producing electron-hole pairs.
      Recently, efficient carrier multiplication has been observed in semiconductor
      quantum dots. In this process, a single, high-energy photon generates multiple
      electron-hole pairs. Rather exotic mechanisms have been proposed to explain the
      efficiency of carrier multiplication in PbSe quantum dots. Using atomistic
      pseudopotential calculations, we show here that the more conventional impact
      ionization mechanism, whereby a photogenerated electron-hole pair decays into a
      biexciton in a process driven by Coulomb interactions between the carriers, can
      explain both the rate (<<1 ps) and the energy threshold ( approximately 2.2 times
      the band gap) of carrier multiplication, without the need to invoke alternative
      mechanisms.

PMID- 17034082
TI  - Bundle-shaped cyclodextrin-Tb nano-supramolecular assembly mediated by C60:
      intramolecular energy transfer.
AB  - A bundle-shaped nano-supramolecular assembly possessing numerous luminescent
      cyclodextrin-Tb polyads and photosensitizing C(60) units has been constructed
      through the end-to-end inclusion complexation of cyclodextrin cavities with
      C(60)s, and its properties have been comprehensively characterized. Further
      investigations on the luminescence properties of the cyclodextrin-Tb polyad and
      the bundle-shaped assembly demonstrate that a pyridine --> Tb --> C(60)
      intramolecular energy transfer process is operative when a solution of the
      assembly is exposed to UV light.

PMID- 17034083
TI  - Level structure of InAs quantum dots in two-dimensional assemblies.
AB  - The electronic level structure of colloidal InAs quantum dots (QDs) in two
      dimensional arrays, forming a QD-solid system, was probed using scanning
      tunneling spectroscopy. The band gap is found to reduce compared to that of the
      corresponding isolated QDs. Typically, the electron (conduction-band) ground
      state red shifts more than the hole (valence-band) ground state. This is assigned
      to the much smaller effective mass of the electrons, resulting in stronger
      electron delocalization and larger coupling between electron states of
      neighboring QDs compared to the holes. This is corroborated by comparing these
      results with those for InAs and CdSe nanorod assemblies, manifesting the effects
      of the electron effective mass and arrangement of nearest neighbors on the band
      gap reduction. In addition, in InAs QD arrays, the levels are broadened, and in
      some cases their discrete level structure was nearly washed out completely and
      the tunneling spectra exhibited a signature of two-dimensional density of states.

PMID- 17034084
TI  - Scanned gate microscopy of a one-dimensional quantum dot.
AB  - We analyze electrostatic interaction between a sharp conducting tip and a thin
      one-dimensional wire, e.g., a carbon nanotube, in a scanned gate microscopy (SGM)
      experiment. The problem is analytically tractable if the wire resides on a thin
      dielectric substrate above a metallic backgate. The characteristic spatial scale
      of the electrostatic coupling to the tip is equal to its height above the
      substrate. Numerical simulations indicate that imaging of individual electrons by
      SGM is possible once the mean electron separation exceeds this scale (typically,
      a few tens of nm). Differences between weakly and strongly invasive SGM regimes
      are pointed out.

PMID- 17034085
TI  - Optically pumped surface-emitting lasing using self-assembled block-copolymer
      distributed Bragg reflectors.
AB  - A thin-film organic laser cavity using a block-copolymer-based one-dimensional
      (1D) photonic crystal was fabricated. Polymeric distributed Bragg reflectors
      (DBRs) were prepared through the self-assembly of a lamellar-forming poly(styrene
      b-isoprene) (PS-b-PI) diblock copolymer having a 1D photonic stop band
      overlapping with the fluorescence spectrum of a gain medium. Optically pumped
      surface-emitting lasing was obtained using poly(methyl methacrylate) (PMMA) doped
      with 1,4-di-(2-methylstyryl)benzene (Bis-MSB) as an organic gain medium and the
      polymeric self-assembled DBR as a spectral-band selective feedback element.

PMID- 17034086
TI  - Early use of PbS nanotechnology for an ancient hair dyeing formula.
AB  - Lead-based chemistry was initiated in ancient Egypt for cosmetic preparation more
      than 4000 years ago. Here, we study a hair-dyeing recipe using lead salts
      described in text since Greco-Roman times. We report direct evidence about the
      shape and distribution of PbS nanocrystals that form within the hair during
      blackening. It is remarkable that the composition and supramolecular organization
      of keratins can control PbS nanocrystal growth inside a hair.

PMID- 17034087
TI  - Properties of a versatile nanoparticle platform contrast agent to image and
      characterize atherosclerotic plaques by magnetic resonance imaging.
AB  - The need for more specific and selective contrast agents for magnetic resonance
      imaging motivated us to prepare a new nanoparticle agent based on high-density
      lipoproteins (HDL). This second generation contrast agent can be prepared in
      three different ways. The HDL nanoparticles (rHDL) were fully characterized by
      FPLC and gel electrophoresis. The flexibility of the platform also allows us to
      incorporate optical probes into rHDL for localization ex vivo by confocal
      fluorescence microscopy. The contrast-agent-containing nanoparticles were
      injected into mice that develop atherosclerotic lesions. Magnetic resonance
      imaging of the animals showed clear enhancement of the atherosclerotic plaques.

PMID- 17034088
TI  - In vivo molecular probing of cellular compartments with gold nanoparticles and
      nanoaggregates.
AB  - Surface-enhanced Raman (SERS) signatures were measured from single living cells
      at different times after the uptake of gold nanoparticles. The spectra are
      indicative of chemical changes in the environment of the nanostructures over
      time. The increase of the SERS signal strength and parallel TEM studies indicate
      the formation of nanoaggregates providing optimum SERS enhancement for
      ultrasensitive probing inside the endosomal compartment. The results have
      implications for medical and biotechnology applications of SERS nanosensors in
      cells.

PMID- 17034089
TI  - Electrokinetic energy conversion efficiency in nanofluidic channels.
AB  - We theoretically evaluate the prospect of using electrokinetic phenomena to
      convert hydrostatic energy to electrical power. An expression is derived for the
      energy conversion efficiency of a two-terminal fluidic device in terms of its
      linear electrokinetic response properties. For a slitlike nanochannel of constant
      surface charge density, we predict that the maximum energy conversion efficiency
      occurs at low salt concentrations. An analytic expression for the regime of
      strong double-layer overlap reveals that the efficiency depends only on the ratio
      of the channel height to the Gouy-Chapman length, and the product of the
      viscosity and the counterion mobility. We estimate that an electrokinetic energy
      conversion device could achieve a maximum efficiency of 12% for simple monovalent
      ions in aqueous solution.

PMID- 17034090
TI  - Electrical conductance of molecular junctions by a robust statistical analysis.
AB  - We propose an objective and robust method to extract the electrical conductance
      of single molecules connected to metal electrodes from a set of measured
      conductance data. Our method roots in the physics of tunneling and is tested on
      octanedithiol using mechanically controllable break junctions. The single
      molecule conductance values can be deduced without the need for data selection.

PMID- 17034091
TI  - Tailoring the interfaces between nematic liquid crystal emulsions and aqueous
      phases via layer-by-layer assembly.
AB  - We report the assembly of polyelectrolyte multilayer (PEM) films at the
      interfaces of thermotropic liquid crystal (LC) droplets dispersed in an aqueous
      phase. Exposure of PEM-coated droplets to surfactant slowed the bipolar-to-radial
      ordering transition of the LCs by 2 orders of magnitude relative to naked
      droplets. This shows that PEMs can be used to influence the interactions of
      analytes with the LC cores of the droplets, allowing tuning of the LC emulsion
      sensing properties.

PMID- 17034093
TI  - Complex buckling instability patterns of nanomembranes with encapsulated gold
      nanoparticle arrays.
AB  - The nanomechanical properties of micropatterned nanomembranes containing gold
      nanoparticle microarrays were investigated with the buckling instability method.
      An unusual, complex pattern of buckling instability was observed for the
      nanoscale polymeric films under compressive stresses. An intriguing two-stage
      wrinkling was observed for these nanoscale films with spatially correlated
      instabilities. Two concurrent strain-dependent buckling modes were observed above
      a certain critical strain. Transformation from conventional transversal buckling
      mode to zigzag buckling is attributed to the development of the biaxial stress
      along the boundary lines for micropatterned areas. The binary buckling pattern
      observed here allowed the "one-shot" evaluation of the elastic moduli of two
      compositionally different regions (with and without gold nanoparticles).

PMID- 17034092
TI  - The role of thickness transitions in convective assembly.
AB  - Here we examine the microscopic details of convective assembly, a process in
      which thin colloidal crystals are deposited on a substrate from suspensions of
      nearly monodisperse spheres. Previously, such crystals have been shown to exhibit
      a strong tendency toward the face-centered cubic structure, which is difficult to
      explain on thermodynamic grounds. Using real-time microscopic visualization,
      electron microscopy, and scanning confocal microscopy, we obtain clues about the
      crystallization mechanism. Our results indicate that the regions at which a
      growing crystal transitions from n to n + 1 layers can play an important and
      previously unrecognized role in the crystallization. For thin crystals, we show
      both from experiment and through simple modeling that these transition regions
      can generate specific crystal structures. In thicker crystals, the
      crystallization is more complicated, but the transition regions must still be
      considered before a complete understanding of convective assembly can be
      obtained.

PMID- 17034094
TI  - Shock-induced localized amorphization in metallic nanorods with strain-rate
      dependent characteristics.
AB  - Classical force-field simulations were used to study the tensile shock-induced
      response of metallic nanorods. The nanorods were found to amorphize at strain
      rate amorphization limits of 1.6% ps(-1) for a 4.0-nm-diameter platinum (Pt)
      nanorod and 1.2% ps(-1) for a 4.0-nm-diameter gold (Au) nanorod, with a length-to
      diameter ratio of 3. Highly localized necking was observed at mid-depth of the
      nanorods at about 2.0% ps(-1). As the strain rates were increased further, the
      neck bifurcated away from the mid-depth toward the nanorod ends, resulting in
      multiple necks at 4.0% ps(-1) and 3.0% ps(-1) for Pt and Au, respectively. At
      strain rates of above 6.0% ps(-1), end delamination took place. The longitudinal
      wave propagation equation was adequate to explain and predict the location of the
      appearance of necks along the nanorod.

PMID- 17034095
TI  - Catalytic membranes prepared using layer-by-layer adsorption of
      polyelectrolyte/metal nanoparticle films in porous supports.
AB  - Layer-by-layer adsorption of polyelectrolytes and gold nanoparticles within
      porous supports provides a convenient method for forming catalytic membranes. The
      polyelectrolyte film effectively immobilizes the gold nanoparticles without
      inhibiting access to catalytic sites, as shown by the similar rate constants for
      nanoparticle-catalyzed 4-nitrophenol reduction in solution and in membranes.
      Modified alumina membranes reduce >99% of 0.4 mM 4-nitrophenol at linear flow
      rates of 0.98 cm/s, and the modification process is also applicable to track
      etched polycarbonate supports.

PMID- 17034096
TI  - Synthesis and electrical characterization of silver nanobeams.
AB  - By slowing the rate of atomic addition to singly twinned seeds, we have grown
      silver nanobeams with lengths of 3-30 mum, widths ranging from 17 to 70 nm, and a
      width to thickness ratio of 1.4. The well-defined dimensions, smooth surface, and
      crystallinity of nanobeams make them promising candidates for studying the
      effects of size on electron transport. With a simple method that allows rapid
      characterization of single nanobeams, we find that even the thinnest nanobeams
      largely retain the low resistivity of bulk silver. Nanobeams can support
      remarkably high current densities of up to 2.6 x 10(8) A cm(-2) before the
      conduction path is broken by the formation of a nanogap.

PMID- 17034097
TI  - Direct patterning of three-dimensional periodic nanostructures by surface-plasmon
      assisted nanolithography.
AB  - The technical applications of three-dimensional (3D) nanostructures demand a
      fabrication technique that is convenient and yet offers design flexibility. We
      describe here a nanofabrication technique called surface-plasmon-assisted three
      dimensional nanolithography (3D-SPAN). By utilizing optical near-field
      interference patterns generated by surface plasmons (SPs), we have fabricated
      different 2D/3D periodic polymeric nanostructures in a typical photolithography
      setup. We have also shown here that the nanostructures fabricated by 3D-SPAN can
      be controlled easily in terms of size, layout, and defects by designing the SPAN
      mask. Because of its design flexibility and fabrication convenience, 3D-SPAN
      could be used to develop "photonics on a chip", where signal processing is
      carried out by photons instead of electrons and be extended to other applications
      of direct-writing 3D functional nanostructures.

PMID- 17034098
TI  - Nucleation and melting from nanovoids.
AB  - Melting in solids containing nanovoids is studied via molecular dynamics
      simulation, and the finite size effects are treated with different size systems.
      For the first time, we have found four typical stages in void melting that are
      different from the melting of bulk materials and nanoparticles. Melting in each
      of the stages is governed by the interplay among different thermodynamic
      mechanisms arising from the changes in the interfacial free energies, the
      curvature of the interface, and the elastic energy induced by the density change
      at melting. As a result, the local melting temperatures show a strong dependence
      on the void size, which is the root cause of the observed complex hierarchical
      melting sequence.

PMID- 17034099
TI  - Formation of rectangularly shaped Pd/Au bimetallic nanorods: evidence for
      competing growth of the Pd shell between the 110 and 100 side facets of Au
      nanorods.
AB  - In this letter, we report the competing growth of a Pd shell on the {110} and
      {100} facets of Au nanorods (Au NRs). This results in the disappearance of
      unstable {110} facets and the formation of rectangularly shaped Pd/Au bimetallic
      nanorods that show only four stable {100} side surfaces. The energy minimization
      to a more stable morphology is believed to be the driving force for the formation
      of the rectangular shape of the Pd shell.

PMID- 17034100
TI  - Ultrafast vibrationally-induced dephasing of electronic excitations in PbSe
      quantum dots.
AB  - Vibrationally induced pure-dephasing of electronic states in PbSe quantum dots
      (QDs) at room temperature is investigated using two independent theoretical
      approaches based on the optical response function and semiclassical formalisms.
      Both approaches predict dephasing times of around 10 fs and reproduce the
      recently measured homogeneous linewidths of optical absorption well. Because
      dephasing slows down with increasing cluster size, the dephasing times calculated
      for the small clusters correspond to the lower end of the experimental data. The
      dephasing is almost independent of the electronic excitation energy and occurs
      faster for biexcitons than single excitons. The dephasing time is roughly
      proportional to the square root of the mass of the lighter atom (Se), suggesting
      that dephasing should be faster in PbS and slower in PbTe relative to PbSe. Core
      atoms produce stronger dephasing than surface atoms. In the collective
      description, pure-dephasing occurs via low-frequency acoustic modes, in support
      of the elastic QD model of dephasing. Because the electron-phonon coupling in
      PbSe QDs is relatively weak compared to other semiconductor nanocrystals, fast
      vibrationally induced dephasing can be expected in semiconductor QDs in general.

PMID- 17034101
TI  - In situ observation of nanograin rotation and deformation in nacre.
AB  - Nacre is a natural nanocomposite material with superior mechanical strength and
      toughness. What roles do the nanoscale structures play in the inelasticity and
      toughening of nacre? Can we learn from this to produce nacre-like nanocomposites?
      Here we report in situ dynamic atomic force microscope observations of nacre with
      aragonite nanograins (nanoparticles) of an average grain size of 32 nm, which
      show that nanograin rotation and deformation are the two prominent mechanisms
      contributing to energy dissipation in nacre. The biopolymer spacing between the
      nanograins facilitates the grain rotation process. The aragonite nanograins in
      nacre are not brittle but deformable.

PMID- 17034102
TI  - All-nanoparticle thin-film coatings.
AB  - All-nanoparticle thin-film coatings that exhibit antireflection, antifogging
      (superhydrophilicity), and self-cleaning properties have been prepared via layer
      by-layer deposition of TiO(2) and SiO(2) nanoparticles. The porosity and chemical
      composition of the coatings were determined using a simple method that is based
      on ellipsometry and does not require any assumptions about the refractive indices
      of the constituent nanoparticles. The presence of nanopores in the TiO(2)/SiO(2)
      nanoparticle coatings results in superhydrophilicity as well as antireflection
      properties. The superhydrophilicity of contaminated coatings could also be
      readily recovered and retained after ultraviolet irradiation.

PMID- 17034103
TI  - Strain-induced self organization of metal-insulator domains in single-crystalline
      VO2 nanobeams.
AB  - We investigated the effect of substrate-induced strain on the metal-insulator
      transition (MIT) in single-crystalline VO(2) nanobeams. A simple nanobeam
      substrate adhesion leads to uniaxial strain along the nanobeam length because of
      the nanobeam's unique morphology. The strain changes the relative stability of
      the metal (M) and insulator (I) phases and leads to spontaneous formation of
      periodic, alternating M-I domain patterns during the MIT. The spatial periodicity
      of the M-I domains can be modified by changing the nanobeam thickness and the
      Young's modulus of the substrate.

PMID- 17034104
TI  - Bulk quantities of single-crystal silicon micro-/nanoribbons generated from bulk
      wafers.
AB  - This Letter demonstrates a strategy for producing bulk quantities of high
      quality, dimensionally uniform single-crystal silicon micro- and nanoribbons from
      bulk silicon (111) wafers. The process uses etched trenches with controlled
      rippled structures defined on the sidewalls, together with angled evaporation of
      masking materials and anisotropic wet etching of the silicon, to produce
      multilayer stacks of ribbons with uniform thicknesses and lithographically
      defined lengths and widths, across the entire surface of the wafer. Ribbons with
      thicknesses between tens and hundreds of nanometers, widths in the micrometer
      range, and lengths of up to several centimeters, can be produced, in bulk
      quantities, using this approach. Printing processes enable the layer by layer
      transfer of organized arrays of such ribbons to a range of other substrates. Good
      electrical properties (mobilities approximately 190 cm(2)V(-1)s(-1), on/off
      >10(4)) can be achieved with these ribbons in thin film type transistors formed
      on plastic substrates, thereby demonstrating one potential area of application.

PMID- 17034105
TI  - Controlled replication of butterfly wings for achieving tunable photonic
      properties.
AB  - The fine structure of the wing scale of a Morpho Peleides butterfly was examined
      carefully, and the entire configuration was completely replicated by a uniform
      Al(2)O(3) coating through a low-temperature ALD process. An inverted structure
      was achieved by removing the butterfly wing template at high temperature, forming
      a polycrystalline Al(2)O(3) shell structure with precisely controlled thickness.
      Other than the copy of the morphology of the structure, the optical property,
      such as the existence of PBG, was also inherited by the alumina replica.
      Reflection peaks at the violet/blue range were detected on both original wings
      and their replica, while a simple alumina coating shifted the reflection peak to
      longer wavelength because of the change of periodicity and refraction index. The
      alumina replicas also exhibited similar functional structures as waveguide and
      beam splitter, which may be used as the building blocks for photonic ICs with
      high reproducibility and lower fabrication cost compared to traditional
      lithography techniques.

PMID- 17034106
TI  - Three-dimensional self-assembly of spherical block copolymer domains into V
      shaped grooves.
AB  - The self-assembly of a spherical-morphology block copolymer into V-shaped grooves
      has been investigated. Although spherical morphology block copolymers typically
      form a bcc sphere array in bulk, the V groove promotes the formation of a well
      ordered fcc close-packed sphere array with the (111) planes of the array parallel
      to the groove walls. The sphere size in the block copolymer adjusts depending on
      the commensurability between the periodicity of the block copolymer and the film
      thickness within the V groove. The top surface of the close-packed array,
      parallel to the substrate, shows a square symmetry, unlike the hexagonal symmetry
      seen in monolayers of spherical domains, which may provide a useful geometry for
      block copolymer lithography.

PMID- 17034107
TI  - Profiling the near field of a plasmonic nanoparticle with Raman-based molecular
      rulers.
AB  - The enhanced local optical fields at the surface of illuminated metallic
      nanoparticles and nanostructures are of intense fundamental and technological
      interest. Here we report a self-consistent measurement of the spatial extent of
      the fringing field above a plasmonic nanoparticle surface. Bifunctional DNA-based
      adsorbate molecules are used as nanoscale optical rulers, providing two distinct
      surface enhanced Raman scattering signals that vary independently in intensity as
      a function of distance from the nanoparticle surface. While the measurement
      technique is calibrated on gold nanoshell surfaces with controlled and
      predictable electromagnetic nanoenvironments, this approach is broadly adaptable
      to a wide range of plasmonic geometries.

PMID- 17034108
TI  - Site-specific fabrication and epitaxial conversion of functional oxide nanodisk
      arrays.
AB  - Nanodisk arrays of technologically important magnetic (CoFe(2)O(4)) and
      ferroelectric (BaTiO(3)) oxides are fabricated on diverse substrates with well
      defined size and separation using the soft-eBL approach. We demonstrate that
      below a certain pattern size, the as-deposited amorphous nanodisks can be readily
      converted into dense, single-crystal form that exhibit cube-on-cube heteroepitaxy
      with respect to the underlying single-crystal substrate. Such single-crystal
      disks show well-defined truncated-pyramid morphology that is consistent with
      Wulff construction. The mechanism of morphology development with the pattern size
      change is discussed. Localized characterization of the crystallinity, chemical
      composition, and magnetic behavior of the CFO nanodisk patterns are carried out
      using analytical transmission electron microscopy and magnetic force microscopy.
      Such solution-based epitaxial conversion of patterned arrays of multifunctional
      oxides has potential for viable cost-effective technological applications.

PMID- 17034109
TI  - Toward intelligent nanosize bioreactors: a pH-switchable, channel-equipped,
      functional polymer nanocontainer.
AB  - To develop an intelligent sensor-effector functionality on the nanoscale, a pH
      switchable, controlled nanoreactor based on amphiphilic copolymer membranes was
      built. The nanovesicles were equipped with bacterial transmembrane ompF pore
      proteins and the pH-sensitive enzyme acid phosphatase, resulting in a switchable
      substrate processing at pH 4-6.5. Ideal pH and substrate concentrations for the
      reaction were determined experimentally. In future, the reactor might be used for
      self-regulating targeted diagnostic and therapeutic applications in medicine.

PMID- 17034110
TI  - Mesoporous membrane templated by a polymeric bicontinuous microemulsion.
AB  - We demonstrate a facile method for preparing a novel nanoporous material with an
      isotropic, three-dimensionally continuous pore structure from a polymeric
      bicontinuous microemulsion precursor, which consists of two immiscible
      homopolymers and the corresponding diblock copolymer. The protocol for the
      generation of nanopores is selective cross-linking of one domain with the
      subsequent removal of the other domain by solvent dissolution.

PMID- 17034111
TI  - 1D nanofabrication with a micrometer-sized laser spot.
AB  - A simple laser-assisted procedure for the fabrication of functional organic
      nanostructures is demonstrated. Native silicon samples are coated with
      alkylsiloxane monolayers and patterned with a focused beam of an Ar(+) laser
      (lambda = 514 nm). After patterning, the coating is chemically functionalized
      following a robust preparation scheme. Despite a laser spot diameter of about 2.5
      mum, this routine allows for the fabrication of well-confined organosiloxane
      stripes with widths below 100 nm. As shown, these structures provide a versatile
      means for building ordered surface architectures of nanoscopic components. In
      particular, gold nanoparticles (d = 16 nm) self-assemble into one-dimensional
      arrangements, such as single chains.

PMID- 17034112
TI  - Interpretation of stochastic events in single molecule conductance measurements.
AB  - The electrical conductance of a series of thiol-terminated alkanes, (1,6
      hexanedithiol (HDT), 1,8-octanedithiol (ODT), and 1,10-decanedithol (DDT)) was
      measured using a modified scanning tunneling microscope break junction technique.
      The interpretation of data obtained in this technique is complicated due to
      multiple effects such as microscopic details of the metal-molecule junctions,
      superposition of tunneling currents, and conformational changes in the molecules.
      A new method called the last-step analysis (LSA) is introduced here to clarify
      the contribution of these effects. In direct contrast to previous work, LSA does
      not require any data preselection, making the results less subjective and more
      reproducible. Finally, LSA was used to obtain the conductance of single molecules
      (HDT, (3.6 x 10(-4))G(o); ODT, (4.4 x 10(-5))G(o); DDT, (5.7 x 10(-6))G(o)). The
      tunneling decay parameter (beta) was calculated, and it was found to be
      approximately 1.0 per carbon atom.

PMID- 17034113
TI  - Control of droplet size in liquid nanodispensing.
AB  - In this Letter, the phenomena and parameters governing the nanoscale dispensing
      of liquid through an apertured atomic force microscope probe milled by focused
      ion beam lithography are characterized in detail. We show that the size of
      deposited droplets can be reproducibly defined by controlling the aperture size
      on the probe and the surface energies of both tip outer wall and substrate
      surface. On the basis of these findings, tips with aperture diameter as small as
      35 nm enabled the deposition of regular arrays of nanodroplets with diameter down
      to 70 nm on an alkylamine-modified surface. The fine control of droplet volumes
      down to a few tens of zeptoliters (10(-21)L) provides a unique tool for creating
      devices and probing the fundamentals of wetting at the nanometer scale.

PMID- 17034114
TI  - Periodic ZnO nanorod arrays defined by polystyrene microsphere self-assembled
      monolayers.
AB  - We demonstrate a low-cost and effective method to fabricate hexagonally
      patterned, vertically aligned ZnO nanorod arrays. Selective wet-etching is used
      to develop the catalyzing gold particle hexagonal pattern with the aid of a
      polystyrene microsphere self-assembled monolayer. The gold particles have tunable
      sizes independent of the polystyrene microsphere's diameter and are inherently
      round in shape. Each ZnO rod is grown individually from a catalyzing site via
      catalyst-initiated epitaxy, and the original hexagonal periodicity is well
      preserved. The rods have flat ends, and the diameters of the rods can be
      controlled well by the amount of source materials. This method provides a
      promising way to create ZnO one-dimensional nanostructures for applications as
      two-dimensional photonic crystal, sensor arrays, nanolaser arrays, and
      optoelectronic devices.

PMID- 17034115
TI  - Size effects on the mechanical behavior of nanoporous Au.
AB  - Recent nanomechanical tests on submicron metal columns and wires have revealed a
      dramatic increase in yield strength with decreasing sample size. Here, we
      demonstrate that nanoporous metal foams can be envisioned as a three-dimensional
      network of ultrahigh-strength nanowires, thus bringing together two seemingly
      conflicting properties: high strength and high porosity. Specifically, we
      characterized the size-dependent mechanical properties of nanoporous gold using a
      combination of nanoindentation, column microcompression, and molecular dynamics
      simulations. We find that nanoporous gold can be as strong as bulk Au, despite
      being a highly porous material, and that the ligaments in nanoporous gold
      approach the theoretical yield strength of Au.

PMID- 17034116
TI  - Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl
      2 proteins.
AB  - A structure-based approach was employed to design a new class of small-molecule
      inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a
      K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound
      5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC(50)
      value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

PMID- 17034117
TI  - Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin
      2(1H)-one as a novel selective androgen receptor modulator.
AB  - The androgen receptor is a member of the extended family of nuclear receptors and
      is widely distributed throughout the body. Androgen therapy is used to compensate
      for low levels of the natural hormones testosterone (T) and dihydrotestosterone
      and consists of administration of T, prodrugs thereof, or synthetic androgens.
      However, currently available androgens have many drawbacks. We identified 6
      dialkylamino-4-trifluoromethylquinolin-2(1H)-ones as orally available tissue
      selective androgen receptor modulators.

PMID- 17034118
TI  - Macrocyclic inhibitors of beta-secretase: functional activity in an animal model.
AB  - A macrocyclic inhibitor of beta-secretase was designed by covalently cross
      linking the P1 and P3 side chains of an isophthalamide-based inhibitor.
      Macrocyclization resulted in significantly improved potency and physical
      properties when compared to the initial lead structures. More importantly, these
      macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a
      murine model.

PMID- 17034119
TI  - Discovery of phenyl acetic acid substituted quinolines as novel liver X receptor
      agonists for the treatment of atherosclerosis.
AB  - A structure-based approach was used to optimize our new class of quinoline LXR
      modulators leading to phenyl acetic acid substituted quinolines 15 and 16. Both
      compounds displayed good binding affinity for LXRbeta and LXRalpha and were
      potent activators in LBD transactivation assays. The compounds also increased
      expression of ABCA1 and stimulated cholesterol efflux in THP-1 cells. Quinoline
      16 showed good oral bioavailability and in vivo efficacy in a LDLr knockout mouse
      model for lesions.

PMID- 17034120
TI  - Benzopyrans are selective estrogen receptor beta agonists with novel activity in
      models of benign prostatic hyperplasia.
AB  - Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent,
      selective binding and agonist function in estrogen receptor beta (ERbeta) in
      vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help
      explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates
      involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no
      effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose,
      consistent with in vitro properties of this molecule.

PMID- 17034121
TI  - Acylguanidines as small-molecule beta-secretase inhibitors.
AB  - BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein
      to liberate Abeta, which aggregates leading to plaque deposits implicated in
      Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors
      of BACE1. Crystallographic studies show that these compounds form unique hydrogen
      bonding interactions with the catalytic site aspartic acids and stabilize the
      protein in a flap-open conformation. Structure-based optimization led to the
      identification of potent analogs, such as 10d (BACE1 IC(50) = 110 nM).

PMID- 17034122
TI  - Configurationally restricted bismacrocyclic CXCR4 receptor antagonists.
AB  - A zinc(II) containing configurationally restricted analogue of bismacrocyclic
      cyclam-type CXCR4 chemokine receptor antagonists has been synthesized and shown
      to adopt only one configuration in solution. The single crystal X-ray structure
      reveals favorable binding to acetate via a bidentate chelation that can be
      related to the proposed interaction with aspartate on the receptor protein
      surface. The zinc(II) complex is highly active against HIV infection in vitro.

PMID- 17034123
TI  - Synthesis and antiviral activity of 5-substituted cytidine analogues:
      identification of a potent inhibitor of viral RNA-dependent RNA polymerases.
AB  - As part of our studies of lethal viral mutagens, a series of 5-substituted
      cytidine analogues were synthesized and evaluated for antiviral activity. Among
      the compounds examined, 5-nitrocytidine was effective against poliovirus (PV) and
      coxsackievirus B3 (CVB3) and exhibited greater activity than the clinically
      employed drug ribavirin. Instead of promoting viral mutagenesis, 5-nitrocytidine
      triphosphate inhibited PV RNA-dependent RNA polymerase (K(d) = 1.1 +/- 0.1
      microM), and this inhibition is sufficient to explain the observed antiviral
      activity.

PMID- 17034124
TI  - Determination of the binding mode of thienopyrimidinedione antagonists to the
      human gonadotropin releasing hormone receptor using structure-activity
      relationships, site-directed mutagenesis, and homology modeling.
AB  - We have investigated the specific interactions of a series thienopyrimidinediones
      with the gonadotropin-releasing hormone receptor (GnRH-R). Competitive
      radioligand binding assays were used to determine the effect of several mutants
      on nonpeptide binding. Distinct interactions were observed in two separate
      regions: the N-terminal end of TM7 and the C-terminal end of TM6. The effects of
      mutants at D302((7.32)) and H306((7.36)) suggest that these residues are part of
      a hydrogen-bond network important for anchoring the nonpeptides. Structure
      activity relationships indicated urea substituents on the 6-(4-aminophenyl) group
      with a trans conformational preference bind with high affinity and are sensitive
      to D302((7.32)) mutations. Another interaction area was found between the N
      benzyl-N-methylamino substituent and L300((6.68)) and Y290((6.58)). These
      interaction sites facilitated the derivation of a model in which a representative
      member of the series was docked into GnRH-R. The model is consistent with known
      SAR and illuminates inconsistencies with previous hypotheses regarding how this
      series interacts with the receptor.

PMID- 17034125
TI  - Extra precision glide: docking and scoring incorporating a model of hydrophobic
      enclosure for protein-ligand complexes.
AB  - A novel scoring function to estimate protein-ligand binding affinities has been
      developed and implemented as the Glide 4.0 XP scoring function and docking
      protocol. In addition to unique water desolvation energy terms, protein-ligand
      structural motifs leading to enhanced binding affinity are included: (1)
      hydrophobic enclosure where groups of lipophilic ligand atoms are enclosed on
      opposite faces by lipophilic protein atoms, (2) neutral-neutral single or
      correlated hydrogen bonds in a hydrophobically enclosed environment, and (3) five
      categories of charged-charged hydrogen bonds. The XP scoring function and docking
      protocol have been developed to reproduce experimental binding affinities for a
      set of 198 complexes (RMSDs of 2.26 and 1.73 kcal/mol over all and well-docked
      ligands, respectively) and to yield quality enrichments for a set of fifteen
      screens of pharmaceutical importance. Enrichment results demonstrate the
      importance of the novel XP molecular recognition and water scoring in separating
      active and inactive ligands and avoiding false positives.

PMID- 17034126
TI  - New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme:
      analysis by SARs and computational docking.
AB  - Structure activity relationships for semicarbazide-sensitive amine
      oxidase/vascular adhesion protein-1 (SSAO/VAP-1) were studied using a library of
      arylalkylamine substrates, with the aim of contributing to the discovery of more
      efficient SSAO substrates. Experimental data were contrasted with computational
      docking studies, thereby allowing us to examine the mechanism and substrate
      binding affinity of SSAO and thus contribute to the discovery of more efficient
      SSAO substrates and provide a structural basis for their interactions. We also
      built a model of the mouse SSAO structure, which provides several structural
      rationales for interspecies differences in SSAO substrate selectivity and reveals
      new trends in SSAO substrate recognition. In this context, we identified novel
      efficient substrates for human SSAO that can be used as a lead for the discovery
      of antidiabetic agents.

PMID- 17034127
TI  - Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an
      isoindolinone scaffold.
AB  - From a set of weakly potent lead compounds, using in silico screening and small
      library synthesis, a series of 2-alkyl-3-aryl-3-alkoxyisoindolinones has been
      identified as inhibitors of the MDM2-p53 interaction. Two of the most potent
      compounds, 2-benzyl-3-(4-chlorophenyl)-3-(3-hydroxypropoxy)-2,3-dihydroisoindol-1
      one (76; IC(50) = 15.9 +/- 0.8 microM) and 3-(4-chlorophenyl)-3-(4-hydroxy-3,5
      dimethoxybenzyloxy)-2-propyl-2,3-dihydroisoindol-1-one (79; IC(50) = 5.3 +/- 0.9
      microM), induced p53-dependent gene transcription, in a dose-dependent manner, in
      the MDM2 amplified, SJSA human sarcoma cell line.

PMID- 17034128
TI  - In-situ synthesis of a tacrine-triazole-based inhibitor of acetylcholinesterase:
      configurational selection imposed by steric interactions.
AB  - Recently, researchers have used acetylcholinesterase (AChE) as a reaction vessel
      to synthesize its own inhibitors. Thus, 1 (syn-TZ2PA6), a femtomolar AChE
      inhibitor, which is formed in a 1:1 mixture with its anti-isomer by solution
      phase reaction from 3 (TZ2) and 4 (PA6), can be synthesized exclusively inside
      the AChE gorge. Our computational approach based on quantum mechanical/molecular
      mechanical (QM/MM) calculations, molecular dynamics (MD), and targeted molecular
      dynamics (TMD) studies answers why 1 is the sole product in the AChE environment.
      Ab initio QM/MM results show that the reaction in the AChE gorge occurs when
      3/azide and 4/acetylene are extended in a parallel orientation. An MD simulation
      started from the final structure of QM/MM calculations keeps the azide's and
      acetylene's parallel orientations intact for 10 ns of simulation time. A TMD
      simulation applied on an antiparallel azide-acetylene conformation flips the
      acetylene easily to bring it to a position that is parallel to azide. A second
      set of QM/MM calculations performed on this flipped structure generates a similar
      minimum-energy path as obtained previously. Even a TMD simulation carried out on
      a parallel azide-acetylene conformation could not deform their parallel
      arrangement. All of these results, thus, imply that inside the AChE gorge, the
      azide group of 3 and the acetylene group of 4 always remain parallel, with the
      consequence that 1 is the only product. The architecture of the gorge plays an
      important role in this selective formation of 1.

PMID- 17034129
TI  - Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2
      inhibition: importance of the quality of the dataset.
AB  - The purpose of this study was to explore the use of detailed biological data in
      combination with a statistical learning method for predicting the CYP1A2 and
      CYP2D6 inhibition. Data were extracted from the Aureus-Pharma highly structured
      databases which contain precise measures and detailed experimental protocol
      concerning the inhibition of the two cytochromes. The methodology used was
      Recursive Partitioning, an easy and quick method to implement. The building of
      models was preceded by the evaluation of the chemical space covered by the
      datasets. The descriptors used are available in the MOE software suite. The
      models reached at least 80% of Accuracy and often exceeded this percentage for
      the Sensitivity (Recall), Specificity, and Precision parameters. CYP2D6 datasets
      provided 11 models with Accuracy over 80%, while CYP1A2 datasets counted 5 high
      accuracy models. Our models can be useful to predict the ADME properties during
      the drug discovery process and are indicated for high-throughput screening.

PMID- 17034130
TI  - Comparative binding energy analysis considering multiple receptors: a step toward
      3D-QSAR models for multiple targets.
AB  - Comparative binding energy analysis, a technique to derive receptor-based three
      dimensional quantitative structure-activity relationships (3D-QSAR), is herein
      extended to consider both affinity and selectivity in the derivation of the QSAR
      model. The extension is based on allowing multiple structurally related receptors
      to enter the X-matrix employed in the derivation of the structure-activity model.
      As a result, a single model common to all of them is obtained that considers both
      intra- and inter-receptor affinity differences for a given congeneric series. We
      applied the technique to a series of 88 3-amidinophenylalanines, binding to
      thrombin, trypsin, and factor Xa (fXa). A single predictive regression model for
      the three receptors involving 202 complexes, with a leave-one out (LOO) cross
      validated Q(2) of 0.689, was obtained, and selectivity requirements were
      investigated. We find that total or partial occupancy of any of the three main
      pockets in the binding site (D-site, P-site, and the rim of the S1-site) leads to
      higher affinity across the family. However, the fact that thrombin can make
      stronger interactions in the P-site, as a result of its exclusive 60-loop, makes
      of this site a specificity pocket for this thrombin. Occupancy of the D-site
      leads to more active inhibitors toward fXa for the same reason, but the model
      does not highlight strongly the D-box because inhibitors are too short to fully
      occupy it. Negative charge density in the neighborhood of position 88 (a Lys
      insertion in thrombin) is found to be a determinant for thrombin recognition.
      These results were consistent with previous studies on selectivity in the
      thrombin/trypsin/fXa system.

PMID- 17034131
TI  - Conformationally restricted dipeptide amides as potent and selective neuronal
      nitric oxide synthase inhibitors.
AB  - Four new conformationally restricted analogues of a potent and selective neuronal
      nitric oxide synthase inhibitor, l-nitroargininyl-l-2,4-diaminobutyramide (1),
      have been synthesized. N(alpha)-Methyl and N(alpha)-benzyl derivatives (3 and 4,
      respectively) of 4-N-(l-Arg(NO(2))-trans-4-amino-l-prolineamide (2) are also
      selective inhibitors, but the potency and selectivity of 3 are weak. Analogue 4
      has only one-third the potency and one-half to one-third the selectivity of 2
      against iNOS (inducible nitric oxide synthase) and eNOS (endothelial nitric oxide
      synthase), respectively. 3-N-(l-Arg(NO)(2))-trans-3-amino-l-prolineamide (6) is
      as potent an inhibitor of nNOS (neuronal nitric oxide synthase) as 2; selectivity
      for nNOS over iNOS is half of that for 2, but the selectivity for nNOS over eNOS
      is almost double that for 2. The corresponding cis-isomer (5) is a weak inhibitor
      of nNOS. These results are supported by computer modeling.

PMID- 17034132
TI  - Impact of species-dependent differences on screening, design, and development of
      MAO B inhibitors.
AB  - The impact of species-dependent differences between human and rat MAO B on
      inhibitor screening was evidenced for two classes of compounds, coumarin and 5H
      indeno[1,2-c]pyridazin-5-one derivatives. All examined compounds have shown a
      greater inhibitor potency toward human MAO B than toward rat MAO B. Moreover, no
      correlation was found between human and rat pIC(50) values. These divergences
      have important implications for the design and development of drugs involved in
      the MAO B metabolic pathway, suggesting that results obtained using rat enzyme
      cannot be extrapolated to human CNS, a priori. Indeed, the selection of a hit
      compound for lead generation could be different using human rather than rat
      enzyme. Moreover, the influence of substituents on the in vitro inhibition of
      human MAO B was markedly different between homogeneous series of coumarin and 5H
      indeno[1,2-c]pyridazin-5-one derivatives, suggesting different binding modes, a
      hypothesis clearly supported by molecular docking simulations of inhibitors into
      the active site of human MAO B.

PMID- 17034133
TI  - Synthesis and structure-activity relationships of carbazole sulfonamides as a
      novel class of antimitotic agents against solid tumors.
AB  - Two series of carbazole sulfonamides related to Combretastatin A4 (1) were
      synthesized and evaluated for antiproliferative activity. Thirteen of the 26 new
      sulfonamides exhibited IC(50) values of <1 muM against CEM leukemia cells. Five
      compounds were evaluated against a panel of eight human tumor cell lines. 9-Ethyl
      N-(3,4,5-trimethoxyphenyl)-carbazole-3-sulfonamide (11a) showed significant
      antitumor activity in two human xenograft models (MCF-7 and Bel-7402).
      Preliminary studies with 11a showed that the mode of action involves arrest of M
      phase cell cycle and induction of apoptosis by increasing expression of p53 and
      promoting bcl-2 phosphorylation. Unexpectedly, 11a only weakly inhibits tubulin
      polymerization, which suggests that the mode of action of 11a differs from 1 and
      involves an unidentified target(s). Also, the SAR information gleaned from ring A
      substituted analogues varies significantly from that of 1. Carbazole sulfonamides
      are a novel promising class of antimitotic agents with clinical development
      potential.

PMID- 17034134
TI  - Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors
      substituted with nitrogen heterocycles.
AB  - In connection with an ongoing investigation of indenoisoquinoline topoisomerase I
      (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing
      di(methoxy) and methylenedioxy substituents was held constant, and new
      derivatives were synthesized with nitrogen heterocycles appended to the lactam
      side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in
      the National Cancer Institute's human cancer cell screen. Some of the more potent
      derivatives were also screened for in vivo activity in a hollow fiber assay. The
      results of these studies indicate that lactam substituents possessing nitrogen
      heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition.
      Molecular modeling of these compounds in complex with DNA and Top1 suggests that
      some of the lactam substituents are capable of interacting with the DNA base
      pairs above and below the site of intercalation and/or with Top1 amino acid
      residues, resulting in increased biological activity.

PMID- 17034136
TI  - Identification of selective, nonpeptidic nitrile inhibitors of cathepsin s using
      the substrate activity screening method.
AB  - The substrate activity screening method, a substrate-based fragment
      identification and optimization method for the development of enzyme inhibitors,
      was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted
      1,2,3-triazole-based aldehyde inhibitors (Wood, W. J. L.; Patterson, A. W.;
      Tsuruoka, H.; Jain, R. K.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 15521
      15527). Replacement of the metabolically labile aldehyde pharmacophore with the
      nitrile pharmacophore provided inhibitors with moderate potency for cathepsin S.
      The inhibitors showed good selectivity over cathepsins B and L but no selectivity
      over cathepsin K. X-ray structures of two crystal forms (1.5 and 1.9 A) of a
      complex between cathepsin S and a triazole inhibitor incorporating a chloromethyl
      ketone pharmacophore guided the design of triazole substrates with increased
      cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K.
      Conversion of select substrates to nitrile inhibitors yielded a low molecular
      weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed >1000-fold
      selectivity over cathepsins B, L, and K.

PMID- 17034135
TI  - Enzyme specific activation of benzoquinone ansamycin prodrugs using
      HuCC49DeltaCH2-beta-galactosidase conjugates.
AB  - To activate prodrugs for cancer treatment, an anti-TAG-72 antibody
      (HuCC49DeltaCH2) was used for delivery of an activation enzyme (beta
      galactosidase) to specifically activate a geldanamycin prodrug (17-AG-C2-Gal)
      against colon cancer. The geldanamycin prodrug 17-AG-C2-Gal was synthesized by
      coupling a galactose-amine derivative with geldanamycin at the C-17 position.
      Molecular docking with two different programs (Affinity and Autodock) showed that
      the prodrug (17-AG-C2-Gal) was unable to bind to Hsp90; however, the product (17
      AG-C2), enzymatically cleaved by beta-galactosidase conjugate, bound to Hsp90 in
      a similar way as geldanamycin and 17-AG. The computational docking results were
      further confirmed in experimental testing by the tetrazolium [3-(4,5
      dimethythiazol-2-yl)]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      assay and mass spectrometry. HuCC49DeltaCH2 was chemically conjugated to beta
      galactosidase. The antibody-enzyme conjugate was able to target tumor antigen TAG
      72 with the well-preserved enzymatic activity to activate 17-AG-C2-Gal prodrug.
      The released active drug 17-AG-C2 was demonstrated to induce up to 70% AKT
      degradation and enhance anticancer activity by more than 25-fold compared to the
      prodrug.

PMID- 17034137
TI  - Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier
      protein reductase from Mycobacterium tuberculosis.
AB  - In view of the worldwide spread of multidrug resistance of Mycobacterium
      tuberculosis, there is an urgent need to discover antituberculosis agent with
      novel structures. InhA, the enoyl acyl carrier protein reductase (ENR) from M.
      tuberculosis, is one of the key enzymes involved in the mycobacterial fatty acid
      elongation cycle and has been validated as an effective antimicrobial target. We
      report here the discovery, through high-throughput screening, of a series of
      pyrrolidine carboxamides as a novel class of potent InhA inhibitors. Crystal
      structures of InhA complexed with three inhibitors have been used to elucidate
      the inhibitor binding mode. The potency of the lead compound was improved over
      160-fold by subsequent optimization through iterative microtiter library
      synthesis followed by in situ activity screening without purification. Resolution
      of racemic mixtures of several inhibitors indicate that only one enantiomer is
      active as an inhibitor of InhA.

PMID- 17034138
TI  - Conformational analysis of an alpha3beta1 integrin-binding peptide from
      thrombospondin-1: implications for antiangiogenic drug design.
AB  - The integrin alpha3beta1 plays important roles in development, angiogenesis, and
      the pathogenesis of cancer, suggesting potential therapeutic uses for antagonists
      of this receptor. Recently, an alpha3beta1 integrin-binding site was mapped to
      residues 190-201 (FQGVLQNVRFVF) of the N-terminal domain of the secreted protein
      thrombospondin-1 (TSP1). This sequence displays diverse biological activities in
      vitro and inhibits angiogenesis in vivo. Herein we describe the NMR solution
      conformation of this segment in both water and dodecylphosphocholine micelles.
      While essentially unstructured in water, a more well-defined conformation is
      populated in micelles, particularly in the C-terminal half of the peptide and
      correlated with increased biological activity of the micellar peptide. The data
      suggested that the residues that are critical for biological activity are
      contained in a structurally well-defined segment of the peptide. These data
      support the role of the NVR motif as a required element of full-length TSP1 for
      specific molecular recognition by the alpha3beta1 integrin.

PMID- 17034139
TI  - Pediatric erythromycins: a comparison of the properties of erythromycins A and B
      2'-ethyl succinates.
AB  - The antibiotic erythromycin A is generally administered to children as a
      suspension of the pro-drug erythromycin A 2'-ethyl succinate. The success of the
      pro-drug depends on (a) elimination of the unacceptably bitter taste of free
      erythromycin, (b) its stability against stomach acid, and (c) its smooth (base
      catalyzed) hydrolysis in the body to yield active erythromycin. We have
      investigated the rates and pathways of acid-catalyzed degradation and base
      catalyzed hydrolysis of the 2'-ethyl succinates of erythromycins A and B.
      Esterification does not protect the drugs against acid-catalyzed degradation in
      solution; however, erythromycin B 2'-ethyl succinate is much more stable than the
      corresponding erythromycin A ester, degrading nearly 40 times more slowly. The
      rates of base-catalyzed hydrolysis in conditions mimicking the blood stream are
      similar for the two pro-drugs. We conclude that erythromycin B 2'-ethyl succinate
      is an attractive prospect as a pediatric erythromycin pro-drug.

PMID- 17034140
TI  - Synthesis, structure-activity relationships, and antitumor studies of 2
      benzoxazolyl hydrazones derived from alpha-(N)-acyl heteroaromatics.
AB  - Recently we have described the antitumor activities of 2-benzoxazolylhydrazones
      derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious
      analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2
      acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized.
      The 2-acylpyridyl hydrazones inhibited in vitro cell proliferation in the nM
      range, whereas the hydrazones derived from the alpha-(N)
      acetyldiazines/quinolines inhibited cell growth in the muM range. Compounds
      tested in the NCI-60 cell assay were effective inhibitors of leukemia, colon, and
      ovarian cancer cells. E-13k [N-benzoxazol-2-yl-N'-(1-isoquinolin-3-yl-ethylidene)
      hydrazine] inhibited the proliferation of MCF-7 breast carcinoma cells more
      efficiently than nontransformed MCF-10A cells. It is not transported by P
      glycoprotein and a weak MRP substrate. Increased concentrations of serum or
      alpha(1)-acid glycoprotein did not reduce the antiproliferative activity of the
      compound. In the in vivo hollow fiber assay, E-13k achieved a score of 24, with a
      net cell kill of OVCAR-3 (ovarian) and SF2-95 (CNS) tumor cells.

PMID- 17034141
TI  - Structure-activity relationship of quinoline derivatives as potent and selective
      alpha(2C)-adrenoceptor antagonists.
AB  - Starting from two acridine compounds identified in a high-throughput screening
      campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and
      tested for their properties on the human alpha(2)-adrenoceptor subtypes
      (alpha(2A), alpha(2B), and alpha(2C)). A number of compounds with good antagonist
      potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities
      over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4
      dimethylpiperazin-1-yl)phenylamino]quinolin-3-yl}methanol 6j had an antagonist
      potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for,
      the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship
      identified a number of structural features, the most critical of which was an
      absolute need for a substituent in the 3-position of the quinoline ring. The 3
      position on the piperazine ring was also found to play an appreciable role, as
      substitutions in that position exerted a significant and stereospecific
      beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing
      the piperazine ring proved difficult, with 1,4-diazepanes representing the only
      viable alternative.

PMID- 17034142
TI  - Synthesis of a highly pure lipid core peptide based self-adjuvanting triepitopic
      group A streptococcal vaccine, and subsequent immunological evaluation.
AB  - We have developed a highly pure, self-adjuvanting, triepitopic Group A
      Streptococcal vaccine based on the lipid core peptide system, a vaccine delivery
      system incorporating lipidic adjuvant, carrier, and peptide epitopes into a
      single molecular entity. Vaccine synthesis was performed using native chemical
      ligation. Due to the attachment of a highly lipophilic adjuvant, addition of 1%
      (w/v) sodium dodecyl sulfate was necessary to enhance peptide solubility in order
      to enable ligation. The vaccine was synthesized in three steps to yield a highly
      pure product (97.7% purity) with an excellent overall yield. Subcutaneous
      immunization of B10.BR (H-2(k)) mice with the synthesized vaccine, with or
      without the addition of complete Freund's adjuvant, elicited high serum IgG
      antibody titers against each of the incorporated peptide epitopes.

PMID- 17034143
TI  - Identification and optimization of anthranilic sulfonamides as novel, selective
      cholecystokinin-2 receptor antagonists.
AB  - A high throughput screening approach to the identification of selective
      cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel
      series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4
      ylsulfonyl)amino]-5-chlorobenzoyl]-piperidine (1; CCK-2R, pK(I) = 6.4).
      Preliminary exploration of the structure-activity relationships around the
      anthranilic ring and the amide and sulfonamide moieties led to a nearly 50-fold
      improvement of receptor affinity and showed a greater than 1000-fold selectivity
      over the related cholecystokinin-1 receptor. Pharmacokinetic evaluation led to
      the identification of 4-[4-iodo-2-[(5-quinoxalinylsulfonyl)amino]benzoyl]
      morpholine, 26d, a compound that demonstrates promising pharmacokinetic
      properties in the rat and dog with respect to plasma clearance and oral
      bioavailability and is a potent inhibitor in vivo of pentagastrin-stimulated acid
      secretion in the rat when dosed orally.

PMID- 17034144
TI  - Structure-activity relationship studies on a novel series of (S)-2beta
      substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for
      in vivo investigation.
AB  - In general, 3alpha-(diphenylmethoxy)tropane (benztropine)-based dopamine uptake
      inhibitors do not demonstrate cocaine-like pharmacological activity in models of
      psychostimulant abuse and have been proposed as potential medications for the
      treatment of cocaine addiction. However, several (S)-2-carboalkoxy-substituted
      3alpha-[bis(4-fluorophenyl)methoxy]tropane analogues were discovered to stimulate
      locomotor activity and substitute in subjects trained to discriminate cocaine,
      suggesting a role of the 2-position substituent in mediating these cocaine-like
      actions. Herein, we describe the synthesis of a series of novel N- and 2
      substituted-3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues.
      Most of these analogues demonstrated high affinity binding to the dopamine
      transporter (DAT; K(i) = 1.8-40 nM), and selectivity over the other monoamine
      transporters and muscarinic M(1) receptors. When the (S)-2-carboalkoxy
      substituent was replaced with (S)-2-ethenyl, the resulting analogue 11
      demonstrated the highest DAT binding affinity in the series (K(i) = 1.81 nM) with
      DAT selectivity over serotonin transporters (SERT; 989-fold), norepinephrine
      transporters (NET; 261-fold) and muscarinic receptors (90-fold). When the 4'-F
      groups of compounds 5 (K(i) = 2.94 nM) and 8 (K(i) = 6.87 nM) were replaced with
      4'-Cl in the (S)-2-carboalkoxy series, DAT binding affinities were slightly
      reduced (K(i) = 12.6 and 14.6 nM for 6 and 7, respectively), yet inhibition of
      dopamine uptake potency remained comparably high (IC(50) range = 1.5-2.5 nM).
      Interestingly, the 4'-Cl analogue (+/-)-6 substituted less in rats trained to
      discriminate cocaine than the 4'-F analogue (+/-)-5. These studies demonstrate
      that manipulation of the 2-, N-, and 3-position substituents in the 3alpha
      (diphenylmethoxy)tropane class of dopamine uptake inhibitors can result in
      ligands with high affinity and selectivity for the DAT, and distinctive in vivo
      pharmacological profiles that cannot be predicted by their effects in vitro.

PMID- 17034145
TI  - Comblike dendrimers containing Tn antigen modulate natural killing and induce the
      production of Tn specific antibodies.
AB  - Comblike glycodendrimers were prepared by the chemoselective ligation of cysteine
      modified glycopeptides (1-7) with a 3-maleimidopropionate-modified linear
      synthetic carrier (8). Glycodendrimers bearing mono-, di-, or tri-Tn clusters (9
      11) were tested as inhibitors using plant and mammalian lectins. In the former
      group, the Codium fragile lectin showed moderate discrimination among 9, 10, and
      11. In the latter group, A and B isoforms of rat NKR-P1 lectin strongly
      discriminated between 9 and 10. 10 caused a 4-fold increase in killing of the NK
      resistant tumor cell lines at concentrations as low as 10(-8) M. Surprisingly, 11
      interacted exclusively with the rat NKR-P1B isoform and inhibited efficiently
      natural killing in both rats and humans, even in the presence of the activating
      compounds 9 and 10. Dinitrophenol haptenization or influenza virus hemagglutinin
      T-cell epitope conjugation increased the immunogenicity of the parent compounds
      and resulted in the production of Tn specific antibodies.

PMID- 17034146
TI  - Dopamine/serotonin receptor ligands. 13: Homologization of a benzindoloazecine
      type dopamine receptor antagonist modulates the affinities for dopamine D(1)-D(5)
      receptors.
AB  - Enlarging the 10-membered ring of 7-methyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2
      f][3]benzazecine (1, LE 300) yielded two homologue antagonists. Their affinities
      and inhibitory activities at D(1)-D(5) receptors were measured by radioligand
      binding experiments and a functional Ca(2+) assay. Compared to 1, phenylpropyl
      homologue 3 was superior in selectivity and affinity for the D(5) subtype (K(i) =
      0.6 nM), whereas the affinity of the indolylpropyl homologue 2 for all subtypes
      decreased. Compounds 2, 3, 10, 11, 17, and 18 are derivatives of novel
      heterocyclic ring systems.

PMID- 17034147
TI  - 2-amino and 2'-aminocombretastatin derivatives as potent antimitotic agents.
AB  - A novel series of 2-amino and 2'-aminocombretastatin derivatives were synthesized
      and evaluated for antitumor activity. Several compounds had excellent
      antiproliferative activity as inhibitors of tubulin polymerization. Compounds 11,
      20, and 21 with IC(50) values of 1.6, 1.7, and 1.8 microM, respectively,
      exhibited more potent inhibition of tubulin polymerization than colchicine and
      approximately as active as combretastatin A-4. They also displayed
      antiproliferative activity with an IC(50) values ranging from 11 to 44 nM in a
      variety of human cell lines from different organs. Structure activity
      relationship information suggests that the NH(2) substituent at the 2-position of
      either ring A or ring B in combretastatin molecular skeleton may play an
      important role in the bioactivity of this series of compounds.

PMID- 17034148
TI  - Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]
      4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent,
      selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV,
      useful for the treatment of diabetes.
AB  - Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug
      class for the treatment of type 2 diabetes. Structure-activity studies of
      substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the
      discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and
      DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM)
      and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate,
      ABT-279, that is orally available, efficacious, and remarkably safe in
      preclinical safety studies.

PMID- 17034149
TI  - Structural basis for the structure-activity relationships of peroxisome
      proliferator-activated receptor agonists.
AB  - Type 2 diabetes has rapidly reached an epidemic proportion becoming a major
      threat to global public health. PPAR agonists have emerged as a leading class of
      oral antidiabetic drugs. We report a structure biology analysis of novel indole
      based PPAR agonists to explain the structure-activity relationships and present a
      critical analysis of reasons for change in selectivity with change in the
      orientation of the same scaffolds. The results would be helpful in designing
      novel PPAR agonists.

PMID- 17034150
TI  - Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-amino 5
      aryl thiophenes as a new class of tubulin inhibitors.
AB  - 2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives
      were synthesized and evaluated for antiproliferative activity, inhibition of
      tubulin polymerization, and cell cycle effects. SARs were elucidated with various
      substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at
      the para-position of the 5-phenyl group showed antiproliferative activity in the
      order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds
      led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of
      apoptosis.

PMID- 17034151
TI  - Much improved upper limit for the rate constant for the reaction of O2+ with N2.
AB  - The rate constant for the reaction of O2+ with N2 to produce NO+ plus NO has been
      measured at 423, 523, and 623 K in a turbulent ion flow tube. Much improved upper
      limits for this reaction at the three temperatures are 2, 4, and 10x10(-21) cm3 s
      1, respectively. These results should render this reaction irrelevant when
      modeling all plasmas involving atmospheric gases.

PMID- 17034152
TI  - The kinetics of thermal decomposition of 1-butyl-3-methylimidazolium
      hexafluorophosphate.
AB  - It is demonstrated that 1-butyl-3-methylimidazolium hexafluorophosphate
      decomposes in a vacuum in the temperature interval of T=(410 to 505) K according
      to zero-order kinetics with the activation energy EA=68.0+/-2.8 kJ.mol-1.

PMID- 17034153
TI  - Respective contributions of polar vs enthalpy effects in the
      addition/fragmentation of mercaptobenzoxazole-derived thiyl radicals and
      analogues to double bonds.
AB  - The formation and the reactivity of three selected sulfur-centered radicals
      formed from mercaptobenzoxazole, mercaptobenzimidazole, and mercaptobenzothiazole
      toward four double bonds (methyl acrylate, acrylonitrile, vinyl ether, and vinyl
      acetate) are investigated. The reversibility of the addition/fragmentation
      reaction in these widely used photoinitiating systems of radical polymerization
      was studied, for the first time, through the measurement of the corresponding
      rate constants by time-resolved laser spectroscopy. The combination of these
      results with quantum mechanical calculations clearly evidences that, contrary to
      previous studies on other aryl thiyl radicals, the addition rate constants (ka)
      are governed here by the polar effects associated with the very high
      electrophilic character of these radicals. However, interestingly, the back
      fragmentation reaction (k-a) is mainly influenced by the enthalpy effects as
      supported by the relationship between the rate constants and the addition
      reaction enthalpy DeltaHR. The addition and fragmentation rate constants
      calculated from the transition state theory (TST) are in satisfactory agreement
      with the experimental ones. Therefore, molecular orbital (MO) calculations
      offered new opportunities for a better understanding of the sulfur-centered
      radical reactivity.

PMID- 17034154
TI  - Activation of electron-transfer reduction of oxygen by hydrogen bond formation of
      superoxide anion with ammonium ion.
AB  - A hydrogen bond formed between the superoxide anion and the ammonium ion (NH4+)
      accelerates electron transfer from the C60 radical anion to oxygen significantly,
      whereas the tetra-n-butylammonium ion has no ability to form a hydrogen bond with
      the superoxidie anion, exhibiting no acceleration of the electron-transfer
      reduction of oxygen. The second-order rate constant of electron transfer from
      C60*- to O2 increases linearly with increasing concentration of NH4+. This
      indicates that O2*- produced in the electron transfer from C60 to O2 is
      stabilized by 1:1 complex formation between O2*- and NH4+. The 1:1 complex formed
      between O2*- and NH4+ was detected by ESR. The binding of O2*- with NH4+ results
      in a positive shift of the reduction potential of O2 with increasing
      concentration of NH4+, leading to the acceleration of electron transfer from C60*
      to O2.

PMID- 17034155
TI  - Vibrational spectra and structures of H2O-NO, HDO-NO, and D2O-NO complexes. An IR
      matrix isolation and DFT study.
AB  - The IR spectra of H2O+NO, HDO+NO, and D2O+NO, isolated in solid neon at low
      temperature have been investigated. Concentration effects and detailed
      vibrational analysis of deuterated and partially deuterated species allowed
      identification of three 1:1 HDO-NO species, two 1:1 D2O-NO species, and only one
      1:1 H2O-NO complex. From comparison between the experimental spectra and the
      results of DFT calculations, it appeared that two different types of weakly bound
      complexes between water and nitric oxide can be formed in a neon matrix. The
      first species is a 1:1 complex where bonding occurs between water hydrogen and
      nitric oxide nitrogen, in which OH-N and OD-N intermolecular bonds are engaged.
      For this complex only DOD-NO, HOD-NO, and DOH-NO isotopic species have been
      experimentally detected and no IR bands of HOH-NO were observed. This result
      could be explained by the fact that the dissociation energy of HOH-NO is lower
      than those of DOD-NO, HOD-NO and DOH-NO. For the second detected 1:1 H2O-NO
      complex and its isotopic variants, the H2O-NO potential surface was explored
      systematically at the B3LYP level, but no stable species corresponding to the
      complex could be calculated. The structure of the second observed 1:1 H2O-NO
      complex results from columbic attractions between water and nitric oxide and
      could be stabilized only in matrix, probably by interaction between NO, water and
      (Ne)n.

PMID- 17034156
TI  - Generation of gas-phase VO2+, VOOH+, and VO2+-nitrile complex ions by
      electrospray ionization and collision-induced dissociation.
AB  - Cationic metal species normally function as Lewis acids, accepting electron
      density from bound electron-donating ligands, but they can be induced to function
      as electron donors relative to dioxygen by careful control of the oxidation state
      and ligand field. In this study, cationic vanadium(IV) oxohydroxy complexes were
      induced to function as Lewis bases, as demonstrated by addition of O2 to an
      undercoordinated metal center. Gas-phase complex ions containing the vanadyl
      (VO2+), vanadyl hydroxide (VOOH+), or vanadium(V) dioxo (VO2+) cation and nitrile
      (acetonitrile, propionitrile, butyronitrile, or benzonitrile) ligands were
      generated by electrospray ionization (ESI) for study by multiple-stage tandem
      mass spectrometry. The principal species generated by ESI were complexes with the
      formula [VO(L)n]2+, where L represents the respective nitrile ligands and n=4 and
      5. Collision-induced dissociation (CID) of [VO(L)5]2+ eliminated a single nitrile
      ligand to produce [VO(L)4]2+. Two distinct fragmentation pathways were observed
      for the subsequent dissociation of [VO(L)4]2+. The first involved the elimination
      of a second nitrile ligand to generate [VO(L)3]2+, which then added neutral H2O
      via an association reaction that occurred for all undercoordinated vanadium
      complexes. The second [UO(L)4]2+ fragmentation pathway led instead to the
      formation of [VOOH(L)2]+ through collisions with gas-phase H2O and concomitant
      losses of L and [L+H]+. CID of [VOOH(L)2]+ caused the elimination of a single
      nitrile ligand to generate [VOOH(L)]+, which rapidly added O2 (in addition to
      H2O) by a gas-phase association reaction. CID of [VONO3(L)2]+, generated from
      spray solutions created by mixing VOSO4 and Ba(NO3)2 (and precipitation of
      BaSO4), caused elimination of NO2 to produce [VO2(L)2]+. CID of [VO2(L)2]+
      produced elimination of a single nitrile ligand to form [VO2(L)]+, a V(V)
      analogue to the O2-reactive V(IV) species [VOOH(L)]+; however, this V(V) complex
      was unreactive with O2, which indicates the requirement for an unpaired electron
      in the metal valence shell for O2 addition. In general, the [VO2(L)2]+ species
      required higher collisions energies to liberate the nitrile ligand, suggesting
      that they are more strongly bound than the [VOOH(L)2]+ counterparts.

PMID- 17034157
TI  - Direct dynamics study on the reaction of N2H4 with F atom: a hydrogen abstraction
      reaction?
AB  - We present a systematic direct ab initio dynamics investigation of the reaction
      between N2H4 and F atom, which is predicted to have three possible reaction
      channels. The structures and frequencies at the stationary points and the points
      along the minimum energy paths (MEPs) of all reaction channels were calculated at
      the UB3LYP/6-31+G(d,p) level of theory. Energetic information of stationary
      points and the points along the MEPs was further refined by means of the
      CCSD(T)/aug-cc-pVTZ method. The calculated results revealed that the first two
      primary channels (N2H4+F-->N2H3+HF) are equivalent and occur synchronously via
      the formation of a pre-reaction complex with Cs symmetry rather than via the
      direct H abstraction. The pre-reaction complex then evolves into a hydrogen
      bonding intermediate through a transition state with nearly no barrier and a high
      exothermicity, which finally makes the intermediate further decompose into N2H3
      and HF. Another reaction channel of minor role (N2H4+F-->NH2F+NH2) was also found
      during the calculations, which has the same Cs pre-reaction complex but forms
      NH2F and NH2 via another transition state with high-energy barrier and low
      exothermicity. The rate constants of these channels were calculated using the
      improved canonical variational transition state theory with the small-curvature
      tunneling correction (ICVT/SCT) method. The three-parameter ICVT/SCT rate
      constant expressions of k(ICVT/SCT) at the CCSD(T)/aug-cc-pVTZ//UB3LYP/6
      31+G(d,p) level of theory within 220-3000 K were fitted as (7.64x10(-9))T (-0.87)
      exp(1180/T) cm3 mole-1 s-1 for N2H4+F-->N2H3+HF and 1.45x10(-12)(T/298)(2.17)
      exp(-1710/T) cm3 mole-1 s-1 for N2H4+F-->NH2F+NH2.

PMID- 17034158
TI  - Absorption cross sections of formaldehyde at wavelengths from 300 to 340 nm at
      294 and 245 K.
AB  - Absorption cross sections for the A1A2-X1A1 electronic transition of formaldehyde
      have been measured by ultraviolet (UV) laser absorption spectroscopy in the
      tropospherically significant wavelength range 300-340 nm, over which HCHO is
      photochemically active. Absorption cross sections are reported at two
      temperatures, 294 and 245 K and at a spectral resolution of 0.0035 nm (0.35 cm
      1). At this resolution, greater peak absorption cross sections are obtained for
      many of the sharp spectral features than were previously reported. To simulate
      atmospheric conditions in the troposphere, the effects of adding a pressure of
      nitrogen of up to 500 Torr and of reduced sample temperature were investigated.
      The overall magnitudes of peak absorption cross sections are largely unaffected
      by the added pressure of nitrogen, but a modest degree of pressure broadening
      (0.2-0.3 cm-1 atm-1) is evident in the line shapes. Computer simulations of
      spectra have been optimized by comparison with wavelength-dependent formaldehyde
      absorption cross sections for each major vibronic band in the chosen wavelength
      range. Experimental and computer simulated spectra at 294 and 245 K are compared
      to test the reliability of the computer simulations for quantification of the
      effects of temperature on absorption cross sections. All experimental absorption
      cross section data and tables of input parameters for spectral simulations are
      available as Supporting Information.

PMID- 17034159
TI  - Diffusion kinetics for methanol in polycrystalline ice.
AB  - Quantitative analyses of the isothermal desorption kinetics from methanol-doped
      H2O films on Pt(111) reveal that transport kinetics for CH3OH in polycrystalline
      ice are much slower than previously reported. They also indicate that MeOH
      displays first-order desorption kinetics with respect to its instantaneous
      surface concentration below 0.1 mole fraction in ice. These observations allow
      isothermal desorption rate measurements to be interpreted in terms of a depth
      profiling analysis providing one-dimensional concentration depth profiles from
      methanol-doped polycrystalline ice films. Using a straightforward approach to
      inhibit ice sublimation, transport properties are extracted from the evolution of
      concentration depth profiles obtained after thermal annealing of binary ice films
      at high temperature. Heterodiffusion coefficients for methanol in polycrystalline
      (cubic) ice Ic films are reported for temperatures between 145 and 195 K and for
      concentrations below 10(-3) mole fraction. Finally, diffusion kinetics for
      methanol in ice are shown to display a very strong concentration dependence that
      may contribute, in addition to variations in laboratory samples microstructure,
      to the disagreements reported in the literature regarding the transport
      properties of ice.

PMID- 17034160
TI  - Estimation of electronic coupling for intermolecular electron transfer from cross
      reaction data.
AB  - Sixty-five electron-transfer reactions including 27 new 0, +1 couples have been
      added to our data set of cross-reactions between 0 and +1 couples, bringing it to
      206 reactions involving 72 couples that have been studied by stopped-flow
      kinetics in acetonitrile containing supporting electrolyte at 25 degrees C,
      formal potentials determined by cyclic voltammetry, and analyzed using Marcus
      cross-rate theory. Perhaps surprisingly, a least-squares analysis demonstrates
      that intrinsic rate constants exist that predict the cross-rate constants to
      within a factor of 2 of the observed ones for 93% of the reactions studied, and
      only three of the reactions have a cross-rate constant that lies outside of the
      factor of 3, that corresponds to a factor of 10 uncertainty in the rate constant
      for an unknown couple. Many triarylamines, which have very high intrinsic
      reactivity, are included among the newly studied couples. The enthalpy
      contribution to the Marcus reorganization energy, lambda'v, has been calculated
      for 46 of the couples studied, at the (U)B3LYP/6-31+G (or for the larger and
      lower barrier compounds, at the less time-consuming (U)B3LYP/6-31G) level. In
      combination with a modified Levich and Dogodnadze treatment that assumes that the
      rate constant is proportional to (KeHab2/lambda1/2) exp[-DeltaG/RT], this allows
      estimation of the electronic coupling (Hab) at the transition state for
      intermolecular electron transfer, (more properly H'ab, the product of the square
      root of the encounter complex formation constant times Hab) for these couples.
      Although the principal factor affecting intermolecular electron-transfer rate
      constants is clearly lambda, H'ab effects are easily detectable, and the dynamic
      range in our estimates of them is over a factor of 600.

PMID- 17034161
TI  - Decomposition and isomerization of 1,2-benzisoxazole: single-pulse shock-tube
      experiments, quantum chemical and transition-state theory calculations.
AB  - Isomerization and decomposition of 1,2-benzisoxazole were studied behind
      reflected shock waves in a pressurized driver, single-pulse shock tube. It
      isomerizes to o-hydroxybenzonitrile, and no fragmentation is observed up to a
      temperature where the isomerization is almost complete (approximately 1040 K at 2
      ms reaction time). The isomerization experiments in this investigation covered
      the temperature range 900-1040 K. The lack of fragmentation is in complete
      contrast to the thermal behavior of isoxazole, where no isomerization was
      observed and the main decomposition products over the same temperature range were
      carbon monoxide and acetonitrile. In a series of experiments covering the
      temperature range 1190-1350 K, a plethora of fragmentation products appear in the
      post shock samples of 1,2-benzisoxazole. The product distribution is exactly the
      same regardless of whether the starting material is 1,2-benzisoxazole or o
      hydroxybenzonitrile, indicating that over this temperature range the 1,2
      benzisoxazole has completely isomerized to o-hydroxybenzonitrile prior to
      fragmentation. Two potential energy surfaces that lead to the isomerization were
      evaluated by quantum chemical calculations. One surface with one intermediate and
      two transition states has a high barrier and does not contribute to the process.
      The second surface is more complex. It has three intermediates and four
      transition states, but it has a lower overall barrier and yields the
      isomerization product o-hydroxybenzonitrile at a much higher rate. The
      unimolecular isomerization rate constants kinfinity at a number of temperatures
      in the range of 900-1040 K were calculated from the potential energy surface
      using transition-state theory and then expressed in an Arrhenius form. The value
      obtained is kfirst=4.15x10(14) exp(-51.7x10(3)/RT) s-1, where R is expressed in
      units of cal/(K mol). The calculated value is somewhat higher than the one
      obtained from the experimental results. When it is expressed in terms of energy
      difference it corresponds of ca. 2 kcal/mol.

PMID- 17034162
TI  - Proton transfers induced by lead(II) in a uracil nucleobase: a study based on
      quantum chemistry calculations.
AB  - Within the context of metal biotoxicity, electrospray ionization mass
      spectrometry experiments (ESIMS) have recently been performed by us on the
      pyrimidine nucleobases (B) uracil and thymine complexed with lead(II) [Int. J.
      Mass. Spectrom. 2005, 243, 279]. Among the ions detected, [Pb(B)-H]+ complexes,
      where the base has been deprotonated, have been identified as producing intense
      signals. In the same study, quantum calculations based on density functional
      theory (DFT) have assessed the complexation sites and energies of [Pb(B)-H]+
      ions. The present DFT investigations aim at giving an understanding on the
      energetics and mechanisms associated with uracil's loss of a proton. We
      specifically assess and quantify the role of lead binding in this process. For
      that purpose, intra- and intermolecular proton transfers have been considered. We
      have found that uracil (U) 1,3-tautomerization can be exergonic when uracil is
      complexed with Pb2+, in opposition to the situation without lead. The
      corresponding intramolecular processes were nonetheless found to occur at
      geological time scales. In contrast, the addition of a second body to [Pb(U)]2+
      complexes, namely OH- or H2O (as found in the initial water droplet of ESIMS
      experiments), gives exergonic and fast uracil 1,3-proton transfers. Finally, we
      have shown that intermolecular proton transfers in uracil-H2O, uracil-OH-, or
      uracil-uracil complexes are able to explain the experimentally detected [Pb(U)
      H]+ ions.

PMID- 17034163
TI  - Molecular motion in crystalline naphthalene: analysis of multi-temperature X-ray
      and neutron diffraction data.
AB  - Single crystals of h8-naphthalene have been examined by both X-ray and neutron
      diffraction over a range of temperatures from 5 to 295 K. The aim of this case
      study was to measure the anisotropic displacement parameters (ADPs) of carbons
      and hydrogens and to interpret them using the model of thermal motion proposed by
      Burgi and Capelli (Acta Cryst. 2000, A56, 403). The traditional rigid-body
      analysis expresses the low-frequency motions in terms of molecular translations
      and librations only, whereas the Burgi-Capelli treatment also includes the high
      frequency internal modes. We show that a considerable improvement occurs by
      representing the internal modes by a single second-rank tensor and that a further
      improvement follows by including a Gruneisen parameter to account for volume
      thermal expansion. By applying the treatment to multi-temperature diffraction
      data, there is a considerable reduction in the ratio of number of adjustable
      parameters/number of independent observations.

PMID- 17034164
TI  - Solvent effects on the photodissociation of formic acid: a theoretical study.
AB  - Photodissociation of aqueous formic acid has been investigated with the CASSCF,
      DFT, and MR-CI methods. Solvent effects are considered as a combination of the
      hydrogen-bonding interaction from explicit H2O molecules and the effects from the
      bulk surrounding H2O molecules using the polarizable continuum model. It is found
      that the hydrogen-bonding effect from the explicit water in the complex is the
      major factor to influence properties of aqueous formic acid, while the bulk
      surrounding H2O molecules has a noticeable influence on the structures of the
      complex. The direct C-O bond fission along the S1 pathway is predicted to be an
      important channel upon photolysis of aqueous formic acid at 200 nm, which is
      consistent with experimental observation that aqueous formic acid dissociates
      predominantly into fragments of HCO and OH. The existence of a dark channel upon
      photolysis of aqueous formic acid at 200 nm is assigned as fast relaxation from
      the S1 Franck-Condon geometry to the T1/S1 intersection and subsequent S1-->T1
      intersystem crossing process. S1-->S0 internal conversion followed by molecular
      elimination to CO+H2O is the most probable primary process for formation of
      carbon monoxide, which was observed with considerable yield upon photolysis of
      aqueous formic acid at 253.7 nm.

PMID- 17034165
TI  - Structure and stability of networked metallofullerenes of the transition metals.
AB  - A DFT investigation of substitutionally doped fullerenes MC59 of second- and
      third-row transition metals shows that their stability increases toward the right
      hand side of the d-block. Whereas the structural deviation from that of C60
      depends on the size of the metal atom, stability is governed by electronic
      properties of the transition metal atom. A range of MC59 compounds of group 6-8
      metals are predicted to have sufficient stability for experimental observation.

PMID- 17034166
TI  - Structure, bonding, and lowest energy transitions in unsymmetrical squaraines: a
      computational study.
AB  - Natural resonance theory (NRT) and natural bond orbital (NBO) analysis have been
      carried out on a simple symmetrical and an unsymmetrical substituted squaraine
      with a view of understanding the structure of the latter type of squaraines. It
      is found that there are some fundamental differences in the structure and bonding
      between these two types of squaraines particularly in the resonance weights and
      delocalization energies. These differences are expected to reflect in the low
      energy transitions and charge transfer in these squaraines. To investigate this,
      the nature of the lowest energy transitions occurring on excitation in
      unsymmetrical squaraines has been studied using high-level symmetry adapted
      cluster-configuration interaction method (SAC/SAC-CI) and compared with reported
      experimental observations. In general the agreement with the experimental data is
      very good. The transition dipole moment always lies on the pi-backbone and is
      quite large in magnitude. The ground state dipole moment in some cases does not
      change in the excited state upon excitation while in some other cases there is a
      large reduction/enhancement in the magnitude indicative of some charge
      rearrangement in this direction. Inclusion of the solvent using the IEFPCM model,
      a slightly better agreement with the experiment is found in some cases. Studies
      are carried out with a different basis set and it is found that the change in
      basis set has very little effect on the transition energies. In the case of weak
      side donor groups attached to the central ring the larger charge transfer to the
      central acceptor ring in general takes place from the O- atoms of the squarylium
      moiety while in the case of strong donors the charge transfer from the O- atoms
      to the central rings drop down. We have not observed any correlation between the
      charge transfer in the excited state to the central ring from the side donor
      groups and the lowest energy excitation in the molecules. Reduction of the HOMO
      LUMO gap (an indication of increase of the diradicaloid character) always leads
      to a bathochromic shift.

PMID- 17034167
TI  - Preferential site of attack on fullerene cations: frontier orbitals and rate
      coefficients.
AB  - An analysis of reaction efficiency is presented for reactions of carbonaceous
      ions and molecules. Our results show that the combination of experimental rate
      coefficient measurements and computations of the condensed Fukui functions of
      frontier molecular orbitals and pyramidal angles of pi orbitals is very useful
      for elucidating the reactive sites on fullerene carbon clusters in the gas phase.

PMID- 17034168
TI  - A new perspective in the Lewis acid catalyzed ring opening of epoxides.
      Theoretical study of some complexes of methanol, acetic acid, dimethyl ether,
      diethyl ether, and ethylene oxide with boron trifluoride.
AB  - Several 1:1, 1:2, and 2:2 complexes between BF3 and CH3OH (Met), CH3COOH (AcA),
      (CH3)2O (DME), (CH3CH2)2O (DEE), and (CH2)2O (EOX) have been studied using ab
      initio (MP2) and density functional theory (DFT) (PBE, B3LYP) methods and the 6
      311++G(3df,2pd) basis set. Geometrical structures and vibrational frequencies are
      reported, in most cases, for the first time. A detailed comparison of the
      vibrational frequencies for the O...BF3 vibrational modes, as well as for the
      nu(OH) band in the methanol and acetic acid complexes with BF3, is performed, and
      the theoretical frequency shifts are compared with the available experimental
      information. Thermochemical properties are calculated by employing counterpoise
      correction to alleviate the basis set superposition error. The DFT enthalpy of
      complexation of the 1:1 complexes results in the order of stability
      (AcA)2>AcA:BF3>DEE:BF3>DME:BF3>Met:BF3>EOX:BF3>(Met)2; in contrast, MP2 shows the
      noticeable difference that the AcA:BF3 complex is much less stable (similar to
      Met:BF3). The order of stability shows that, even though acetic acid prefers
      dimerization to complexation with BF3, the case is exactly the opposite for
      methanol. In both cases, the interaction of BF3 with the dimer gives rise to very
      stable trimers. However, in contrast to the interaction of BF3 with the methanol
      dimer being stronger than that with the monomer, the interaction of BF3 with the
      acetic acid dimer is weaker than that with the monomer. The relative strength of
      the complexes, discussed in the context of BF3-catalyzed ring opening of
      epoxides, suggests that the effect of the catalyst in a nonprotogenic solvent
      should be more properly ascribed to activation of the nucleophile instead of
      activation of the epoxide.

PMID- 17034169
TI  - On the electronic origin of strain energy: QTAIM study of perfluorocycloalkanes.
AB  - The strain energies (SE) of the five smallest perfluorocycloalkanes (c-CnF2n;
      n=3, 4, 5, 6, and 7) were calculated by means of several homodesmotic processes
      using B3LYP/6-31++G(d,p) optimized molecular energies. These values were compared
      with the energy difference between the linear and cyclic CF2 groups calculated by
      means of the quantum theory of atoms in molecules (QTAIM) applied on charge
      densities obtained at the same computational level. The differences between the
      values computed with both methods vary from 255 (n=3) to 629 (n=7) kJ mol-1.
      These differences arise because QTAIM-computed SE contain the energy involved in
      opening the ring to give rise to nearly transferable central CF2 fragments of
      linear perfluoroalkanes, whereas homodesmotic energies contain energy terms
      corresponding to transformation of nontransferable linear CF2 fragments and a
      ring-opening energy, which depending on the process, transforms CF2 cyclic
      compounds into nearly transferable or nontransferable linear CF2 groups.

PMID- 17034170
TI  - Theoretical study of hydrogen bonding interaction in nitroxyl (HNO) dimer:
      interrelationship of the two N-H...O blue-shifting hydrogen bonds.
AB  - The hydrogen bonding interactions of the HNO dimer have been investigated using
      ab initio molecular orbital and density functional theory (DFT) with the 6
      311++G(2d,2p) basis set. The natural bond orbital (NBO) analysis and atom in
      molecules (AIM) theory were applied to understand the nature of the interactions.
      The interrelationship between one N-H...O hydrogen bond and the other N-H...O
      hydrogen bond has been established by performing partial optimizations. The dimer
      is stabilized by the N-H...O hydrogen bonding interactions, which lead to the
      contractions of N-H bonds as well as the characteristic blue-shifts of the
      stretching vibrational frequencies nu(N-H). The NBO analysis shows that both
      rehybridization and electron density redistribution contribute to the large blue
      shifts of the N-H stretching frequencies. A quantitative correlations of the
      intermolecular distance H...O (r(H...O)) with the parameters: rho at bond
      critical points (BCPs), s-characters of N atoms in N-H bonds, electron densities
      in the sigma*(N-H), the blue-shift degrees of nu(N-H) are presented. The
      relationship between the difference of rho (|Deltarho|) for the one hydrogen bond
      compared with the other one and the difference of interaction energy (DeltaE) are
      also illustrated. It indicates that for r(H...O) ranging from 2.05 to 2.3528 A,
      with increasing r(H...O), there is the descending tendency for one rho(H...O) and
      the ascending tendency for the other rho(H...O). r(H...O) ranging from 2.3528 to
      2.85 A, there are descending tendencies for the two rho(H...O) with increasing
      r(H...O). On the potential energy surface of the dimer, the smaller the
      difference between one rho(H...O) and the other rho(H...O) is, the more stable
      the structure is. As r(H...O) increases, the blue-shift degrees of nu(N-H)
      decrease. The cooperative descending tendencies in s-characters of two N atoms
      with increasing r(H...O) contribute to the decreases in blue-shift degrees of
      nu(N-H). Ranging from 2.05 to 2.55 A, the increase of the electron density in one
      sigma*(N-H) with elongating r(H...O) weakens the blue-shift degrees of nu(N-H),
      simultaneously, the decrease of the electron density in the other sigma*(N-H)
      with elongating r(H...O) strengthens the blue-shift degrees of nu(N-H). Ranging
      from 2.55 to 2.85 A, the cooperative ascending tendencies of the electron
      densities in two sigma*(N-H) with increasing r(H...O) contribute to the decreases
      in blue-shift degrees of nu(N-H).

PMID- 17034171
TI  - The singlet-triplet gap in trimethylenmethane and the ring-opening of
      methylenecyclopropane: a multireference Brillouin-Wigner coupled cluster study.
AB  - We performed an ab initio study of the singlet-triplet gap in trimethylenmethane
      (TMM) and of the ring-opening of methylenecyclopropane by the multireference BWCC
      method. Since the singlet states of TMM and intermediates between TMM and
      methylenecyclopropane have a strong multiconfigurational character, it is
      necessary to use a multireference method. The cc-pVDZ and cc-pVTZ basis sets were
      used. We compared our results with experiments, where available, and with
      previous calculations performed by MCSCF and spin-flip coupled-cluster-type
      methods.

PMID- 17034172
TI  - Experimental and molecular dynamics studies of dysprosium(III) salt solutions for
      a better representation of the microscopic features used within the binding mean
      spherical approximation theory.
AB  - This work is aimed at a predictive description of the thermodynamic properties of
      actinide(III) salt solutions at high concentration and 25 degrees C. A new
      solution of the binding mean spherical approximation (BIMSA) theory, based on the
      Wertheim formalism, for taking into account 1:1 and also 1:2 complex formation,
      is used to reproduce, from a simple procedure, experimental osmotic coefficient
      variation with concentration for three binary salt solutions of the same
      lanthanide(III) cation: dysprosium(III) perchlorate, nitrate, and chloride. The
      relevance of the fitted parameters is discussed, and their values are compared
      with available literature values. UV-vis/near-IR, time-resolved laser-induced
      fluorescence spectroscopy experiments, and molecular dynamics (MD) calculations
      were conducted for dilute to concentrated solutions (ca. 3 mol.kg-1) for a study
      of the microscopic behavior of DyCl3 binary solutions. Coupling MD calculations
      and extended X-ray absorption fine structure led to the determination of reliable
      distances. The MD results were used for a discussion of the parameters used in
      the BIMSA.

PMID- 17034173
TI  - Transient oxygen clathrate-like hydrate and water networks induced by magnetic
      fields.
AB  - Recently, careful experiments of oxygen-dissolved pure water treated by high
      magnetic fields showed indirectly the existence of magnetic field-affecting water
      (MFA water), which brought about a decrease in the contact angle of water on
      metals, an increase in the electrolytic potential of water, inhibition of metal
      corrosion, and changes in the crystal structure of calcium carbonate due to
      magnetic treatment. Here we report the infrared and Raman spectroscopic evidence
      indicating quasi-stable structures in the MFA water; oxygen clathrate-like
      hydrate and developed water networks, which were induced by magnetic interactions
      while a vacuum-distilled water, followed by oxygen exposure, crossed a steady
      magnetic field. The mechanism of MFA water formation and survival under thermal
      fluctuation is a challenging problem for the science community.

PMID- 17034174
TI  - Comparison of intra- vs intermolecular long-range electron transfer in crystals
      of ruthenium-modified azurin.
AB  - Selective metal-ion incorporation and ligand substitution are employed to control
      whether electrons tunnel over intra- or intermolecular separations in crystals of
      P. aeruginosa azurin modified with Ru-polypyridine complexes. Cu(1+)-to-Ru3+
      electron transfer (ET) across a specific protein-protein interface in the crystal
      lattice has a time constant 5-10 times longer than ET between the same donor and
      acceptor within a single protein (tauET = 5 vs 0.5-1.0 micros). Slower
      intermolecular ET agrees well with a longer distance between redox centers across
      the inter-protein (18.9 A) compared to the intra-protein separation (17.0 A) and
      indicates that the closest donor/acceptor pair dominates crystal ET. Lowering the
      crystal pH accelerates inter-protein ET (tauET = 1.0 micros) but not intra
      protein ET. Faster inter-protein ET likely results from a pH-induced peptide bond
      flip that perturbs hydrogen bonding in the path between Ru and Cu centers on
      adjacent molecules.

PMID- 17034175
TI  - Assembly of linear clusters of iodobenzene dimers on Cu(110).
AB  - Low-temperature STM observations of the low-coverage chemisorption behavior of
      iodobenzene on Cu(110) are presented at two annealing temperatures. When a random
      distribution of isolated iodobenzene molecules deposited at T < 100 K is annealed
      to approximately 170 K, the undissociated molecules assemble into chainlike
      clusters composed of identical subunits. An STM tip-induced dissociation reaction
      is used to determine that the individual units in the chains are composed of
      pairs of iodobenzene molecules. A model is proposed in which iodine atoms on each
      member of the pair are directed toward one another. The driving force for the
      formation of such clusters is suggested to be the dispersion interactions between
      the polarizable iodobenzene molecules.

PMID- 17034176
TI  - Acoustic multibubble cavitation in water: A new aspect of the effect of a rare
      gas atmosphere on bubble temperature and its relevance to sonochemistry.
AB  - Acoustic cavitation generates transient microbubbles with extremely high
      temperatures and high pressures, which can provide unique reaction routes. The
      maximum bubble temperature attained is widely known to be dependent on the
      polytropic index and thermal conductivity of the dissolved gas. Here, we show for
      the first time experimental evidence that the bubble temperature induced by a
      high frequency ultrasound is almost the same among different rare gases and the
      chemical efficiency is in proportion to the gas solubility of rare gases, which
      would be closely related to the number of active bubbles.

PMID- 17034178
TI  - Spontaneous formation of triptycene supramolecules on surfaces.
AB  - In the limit of weak molecular interaction with an inorganic surface, noncovalent
      interactions between molecules dominate the nucleation and thin-film growth.
      Here, we report on the formation of three-dimensional triptycene clusters with a
      particularly stable structure. Once formed at the early stage of molecular
      adsorption, the clusters are stable for all temperatures until desorption.
      Furthermore, the clusters diffuse and nucleate as individual entities, therefore
      constituting building blocks for the later thin-film formation. High resolution
      scanning tunneling microscopy images indicate that the cluster is stabilized by C
      H-pi interactions. The formation of such molecular structures at a surface is
      possible because the three-dimensional structure of the triptycene molecule leads
      to a very weak and mobile adsorption state. These results show that it is
      possible to investigate complex pathways in the formation of three-dimensional
      supramolecules at surfaces using a scanning tunneling microscope.

PMID- 17034177
TI  - trans-cis Photoisomerization of a photoactive yellow protein model chromophore in
      crystalline phase.
AB  - We have studied the photoinduced trans/cis isomerization of the protonated form
      of p-hydroxycinnamic thiophenyl ester, a model chromophore of the photoactive
      yellow protein (PYP), in crystalline phase, by both fluorescence and infrared
      spectroscopies. The conversion from trans to cis configuration is revealed by a
      shift of the fluorescence peak and by inspection of the infrared maker bands. The
      crystal packing apparently stabilizes the cis photoproduct, suggesting different
      environmental effects from the solvent molecules for this model chromophore in
      liquid solutions or from the amino acid residues for the PYP chromophore.

PMID- 17034179
TI  - When does the Michaelis-Menten equation hold for fluctuating enzymes?
AB  - Enzymes are dynamic entities: both their conformation and catalytic activity
      fluctuate over time. When such fluctuations are relatively fast, it is not
      surprising that the classical Michaelis-Menten (MM) relationship between the
      steady-state enzymatic velocity and the substrate concentration still holds.
      However, recent single-molecule experiments have shown that this is the case even
      for an enzyme whose catalytic activity fluctuates on the 10(-4)-10 s range. The
      purpose of this paper is to examine various scenarios in which slowly fluctuating
      enzymes would still obey the MM relationship. Specifically, we consider (1) the
      quasi-static condition (e.g., the conformational fluctuation of the enzyme
      substrate complex is much slower than binding, catalysis, and the conformational
      fluctuations of the free enzyme), (2) the quasi-equilibrium condition (when the
      substrate dissociation is much faster than catalysis, irrespective of the time
      scales or amplitudes of conformational fluctuations), and (3) the conformational
      equilibrium condition (when the dissociation and catalytic rates depend on the
      conformational coordinate in the same way). For each of these scenarios, the
      physical meaning of the apparent Michaelis constant and catalytic rate constant
      is provided. Finally, as an example, the theoretical analysis of a recent single
      molecule enzyme assay is considered in light of the perspectives presented in
      this paper.

PMID- 17034180
TI  - Aromatic superclusters from all-metal aromatic and antiaromatic monomers, [Al4]2-
      and [Al4]4-.
AB  - Calculations on the structures of dimers of all-metal aromatic and anti-aromatic
      molecules such as (Al4(2-)) and (Al4(4-)) reveal that, unlike their organic
      counterparts such as benzene and cyclobutadiene which form pi-stacked complexes,
      these molecules form new clusters with no reminiscence of the original units.
      These clusters have a very large binding energy and can be further stabilized
      through charge-balance by counterions and solvents.

PMID- 17034181
TI  - Vertically aligned dense carbon nanotube growth with diameter control by block
      copolymer micelle catalyst templates.
AB  - We have grown a dense array of vertically aligned carbon nanotubes (CNTs) with a
      controlled distribution of diameters by using block copolymer micelles to form
      and pattern catalyst particles. The block copolymer poly(styrene-block-acrylic
      acid) (PS16500-PAA4500) was dissolved in toluene to form micelles and then loaded
      with FeCl3. The metal-loaded micelles were spin-coated on Si and then thermally
      treated to remove the polymer. Using this process, we produced surfaces patterned
      with iron oxide catalyst particles with particle densities ranging from 1400
      microm(-2) to 3800 microm(-2) and a size distribution of (6.9 +/- 0.8) nm. CNT
      growth by thermal chemical vapor deposition was then performed on these samples.
      The low-density catalyst sample produced unaligned, low-density CNTs, whereas the
      high-density catalyst sample produced vertically aligned, dense CNTs about 10
      microm in length. Transmission electron microscopy revealed that the CNTs
      typically had double and triple graphitic layers with normally distributed
      diameters of (4.5 +/- 1.1) nm. For comparison, CNTs grown from the standard
      approach of blanket Fe films had a wide distribution of diameters between 6 and
      21 nm. This catalyst preparation approach dramatically sharpens the size
      distribution of CNTs, compared to standard approaches, and provides a simple
      means of controlling the areal density of CNTs.

PMID- 17034182
TI  - Ultrafast vibrational spectroscopy of the flavin chromophore.
AB  - Ultrafast time-resolved infrared (TRIR) spectra of flavin adenine dinucleotide
      (FAD) and the anion of lumiflavin (Lf-) are described. Ground-state recovery and
      excited-state decay of FAD reveal a common dominant ultrafast relaxation and a
      minor slower component. The Lf- transient lacks a fast component. No intermediate
      species are observed, suggesting that the quenching mechanism is internal
      conversion promoted by interaction of the adenine and isoalloxazine rings in FAD.
      Modes are assigned, and the potential for extension of the TRIR method to
      photoactive proteins is discussed.

PMID- 17034183
TI  - Photoinduced molecular transport in biological environments based on dipole
      moment fluctuations.
AB  - Consideration is given to the possibility of a molecule moving unidirectionally
      in an electric field of a polar periodic substrate as a result of the
      fluctuations of molecular dipole moment occurring on the photoexcitation of the
      molecule. As estimated for such motion, molecules with sufficiently long
      fluorescence and strongly differing dipole moments in the ground and excited
      states can move with an average velocity of the same order as that typical of
      protein motors such as kinesin. This effect results from the mutual compensation
      of two opposite factors acting in dipole photomotors, namely, a lower energy of
      interaction with the substrate relative to that for protein motors and a shorter
      excited-state lifetime as compared with the duration of the hydrolytic splitting
      of adenosinetriphosphate in protein motors.

PMID- 17034184
TI  - Long-lived interfacial vibrations of water.
AB  - We have observed long-lived OH-stretch (nu(OH)) excitations (v = 1) in water
      during ultrafast laser ablation by a mid-infrared pulse tuned to the nu(OH)
      absorption maximum. The spectrum of excitations is measured using incoherent anti
      Stokes Raman spectroscopy. Relative to the equilibrium water spectrum, these
      excitations evidence a narrowed (100 cm(-1) fwhm) and blue-shifted (3600 cm(-1)
      peak) transition. The excited-state lifetime is T1 > 200 ps, compared to 0.2 ps
      in bulk water. In the early stages of the ablation process, the water mean
      density decreases rapidly, which breaks up the hydrogen bonding. The long-lived
      species is attributed to nu(OH) excitations on water molecules associated with
      interfaces, having broken hydrogen bonds which cannot be rapidly reformed as in
      the liquid state.

PMID- 17034185
TI  - Chemical functionalization of magnetic carbon-encapsulated nanoparticles based on
      acid oxidation.
AB  - Carbon-encapsulated nickel nanoparticles were used as the representative magnetic
      carbon-encapsulated nanoparticles for chemical functionalization. After oxidation
      with the mixed acid of H2SO4/HNO3 under a moderate ultrasonic bath, carboxylic
      acid groups (-COOH) were effectively generated on the fullerene-like carbon
      shells, which in turn were utilized to covalently link octadecylamine through an
      amide reaction. The whole chemical process is well characterized by many methods
      such as Fourier transform infrared spectroscopy, X-ray photoelectron
      spectroscopy, thermogravimetry-differential scanning calorimetry, transmission
      electron microscopy, and so on, and the self-consistent experimental results were
      obtained. The results suggested that the magnetic nanoparticles could be well
      protected, while their magnetic properties could be utilized to guide the
      transfer of the grafted functional species on the particle surface. This provides
      many possibilities for potential applications in chemical and biochemical fields.

PMID- 17034186
TI  - A neutron scattering and nuclear magnetic resonance study of the structure of
      GeO2-P2O5 glasses.
AB  - Germanophosphate (GeO2-P2O5) glasses were studied with neutron diffraction,
      phosphorus, and oxygen nuclear magnetic resonance, calorimetry, viscosity
      measurements, and first-principles calculations. These data sets were combined to
      propose a structural model of GeO2-P2O5 glasses, which includes tetrahedrally
      coordinated phosphorus, formation of octahedrally coordinated germanium as P2O5
      content increases, an absence of trigonally coordinated oxygen, and hence an
      absence of rutile-like GeO2 domains. The structural model was then used to
      propose explanations for both the observed composition dependence of the glass
      transition temperature and the fragility of the GeO2-P2O5 liquids.

PMID- 17034187
TI  - Unconventional zigzag indium phosphide single-crystalline and twinned nanowires.
AB  - Unconventional zigzag indium phosphide (InP) single-crystalline and twinned
      nanowires were produced via thermal evaporation of indium phosphide in the
      presence of zinc selenide. The structure and morphology of the as-synthesized
      products were characterized by X-ray diffraction, scanning electron microscopy,
      and transmission electron microscopy. Studies found that two type of nanowires
      exist in the products, namely, the periodic-rhombus-decorated single-crystalline
      InP (type I) nanowires and jagged twinned InP (type II) nanowires. Both of them
      have preferential 111 growth directions. The optical properties were also
      investigated at room temperature, and they show that the nanowires display a
      strong emission at approximately 750 nm, which is quite different from that
      observed in all previous reports related to the InP nanostructures.

PMID- 17034188
TI  - Combining small angle neutron scattering (SANS) and fluorescence correlation
      spectroscopy (FCS) measurements to relate diffusion in agarose gels to structure.
AB  - Small angle neutron scattering (SANS) and fluorescence correlation spectroscopy
      (FCS) measurements were carried out on agarose hydrogels to link their
      microscopic structure to the diffusivity of solutes at different scales. SANS
      allowed for the determination of the distribution of void volumes within the
      gels. They were shown to be compatible with a random network of cylindrical
      fibers as described by the Ogston model. FCS measured solute diffusivity in
      spaces similar in size to the void volumes, and thus, the results reflected the
      gel heterogeneity. Solute diffusivity was predicted by modeling the gel as
      microscopic geometrical cells. Variations in the diffusivity of solutes of
      different sizes could be predicted from the structural parameters of the gel
      using theory, taking into account obstruction by cylindrical cells and solute
      hydrodynamics. Prediction of the FCS autocorrelation functions for solutes from a
      cell model demonstrated a lack of sensitivity of this technique for
      multicomponent analysis.

PMID- 17034189
TI  - Dynamics of alkyl ammonium intercalants within organically modified
      montmorillonite: Dielectric relaxation and ionic conductivity.
AB  - The low-frequency (0.01 Hz-10 MHz) dynamic characteristics of alkyl quaternary
      ammonium exchanged montmorillonite (SC20A) were investigated to determine the
      correlation between temperature-dependent changes in the interlayer structure and
      collective mobility of the surfactant. From 25 to 165 degrees C, SC20A exhibits
      two interlayer transitions, one ascribed to the melting of the intercalated alkyl
      chains of the surfactant (20-40 degrees C) and another associated with an abrupt
      decrease in the interlayer's coefficient of thermal expansion (100 degrees C).
      For this temperature range, the excess surfactant and residual electrolytes
      present in commercially manufactured SC20A enhance the direct current
      conductivity and increase low-frequency space-charge polarization, which is
      believed to occur across percolation paths established by the surfaces of the
      SC20A crystallites. In contrast, a higher-frequency relaxation, which was less
      sensitive to process history and impurity content, is ascribed to relaxation
      within the interlayer at the surfactant-aluminosilicate interface electrostatic
      couple. The temperature dependence of these dielectric relaxations indicated a
      drastic increase in mobility as the interlayer organic phase transitions from
      static and glasslike into molten and mobile. Overall, SC20A displayed features of
      alternating current universality, including time-temperature superposition,
      common in other types of disordered ion-conducting media. The presence of long
      range transport and its sensitivity to low amounts of impurities imply that from
      a dynamic perspective the local environment of the surfactants are substantially
      diverse and a minority fraction, such as at the edge of the crystallite (gallery
      and aluminosilicate layer), may dominate the lower-frequency dielectric response.

PMID- 17034190
TI  - Structural, magnetic, and magnetoresistive properties of electrodeposited Ni5Zn21
      alloy nanowires.
AB  - Ni5Zn21 alloy nanowires were fabricated through template-assisted electrochemical
      deposition method. The morphology and microstructures of as-deposited nanowires
      were determined by field-emission scanning electron microscope (FE-SEM), X-ray
      diffraction (XRD), high-resolution transmission electron microscope (HRTEM),
      electron diffraction (ED), and electron probe microanalysis (EPMA). The accurate
      composition was measured via induced coupling plasma atomic emission
      spectroscopy. SEM results show that Ni5Zn21 nanowires are deposited in most of
      the nanopores of the template, and they are continuous and dense throughout the
      whole length. The XRD result demonstrates that the nanowires are mainly composed
      of a cubic gamma phase Ni5Zn21 alloy, but there also exists a trace of Zn-rich
      eta phase. HRTEM and ED reveal that the alloy nanowires are polycrystalline with
      the crystallite size of several tens of nanometers. EPMA of a single nanowire
      illustrates that there exist Ni-rich microzones in as-deposited nanowires.
      Subsequent magnetic measurements of the array also confirmed the existence of
      them. In addition, it can be further inferred that the shape of Ni-rich
      microzones is probably barlike or disklike, from the anisotropy of zero field
      cooling/field cooling (ZFC/FC) curves as well as the vortex magnetization
      behavior of the Ni5Zn21 nanowire array. The low-temperature magnetoresistance of
      the Ni5Zn21 nanowire array was also measured. Giant magnetoresistance instead of
      anisotropic magnetoresistance is suggested to be responsible for contributing to
      the magnetoresistance.

PMID- 17034191
TI  - Evaluation of a new force field for describing the adsorption behavior of alkanes
      in various pure silica zeolites.
AB  - The recently proposed united atom force field by Dubbeldam et al. (Phys. Rev.
      Lett. 2004, 93, 088302) for the adsorption of alkanes in MFI-type zeolites was
      extended to other zeolites in this work. Its applicability to FER-type zeolites
      was evaluated in detail, for which the Henry coefficients, the isosteric heat of
      adsorption, the adsorption isotherms, as well as the locations of alkanes in the
      FER-type zeolites were computed and compared to experimental values. The results
      show that the new force field works well for FER zeolites. Furthermore, its
      applicability to MWW-, MTW-, CFI-, LTA-, and STF-type zeolites was investigated,
      and we found that the experimental isotherms could be accurately predicted except
      for STF-type zeolites. This work shows that the new united atom force field
      proposed by Dubbeldam et al. is applicable to most pure silica zeolites.

PMID- 17034192
TI  - Porogen approach for the fabrication of plasma-polymerized nanoporous
      polysiloxane films.
AB  - Nanoporous polysiloxane films were fabricated by plasma polymerization of
      hexamethyldisiloxane mixed with cyclohexane under different conditions. The pores
      were generated through the elimination of carbonaceous aggregates (porogen) by
      annealing at 600 degrees C. Results of spectroscopic ellipsometry, Fourier
      transform infrared spectroscopy, and positron annihilation lifetime spectroscopy
      suggest that not only film porosity but also average pore size depends on the
      amount of the decomposable porogen. The pore size was controllable in a range
      between 0.6 and 1.0 nm in radius by proper selection of the substrate temperature
      and precursor composition.

PMID- 17034193
TI  - Characterization of the metal-organic framework compound Cu3(benzene 1,3,5
      tricarboxylate)2 by means of 129Xe nuclear magnetic and electron paramagnetic
      resonance spectroscopy.
AB  - 129Xe NMR measurements of adsorbed xenon are shown for the first time to be a
      suitable tool to characterize the porosity and the properties of the metal
      organic framework Cu3(BTC)2(H2O)3 (BTC = benzene 1,3,5-tricarboxylate). The NMR
      experiments are performed at room temperature and over a wide range of xenon
      pressure and on two different synthesized Cu3(BTC)2 samples. 129Xe NMR results
      reveal that in dependence on the kind of the synthesis pathway either one or two
      signals are observed which can be attributed to two kinds of fast exchange of
      xenon atoms in two pores with different pore sizes. Coadsorption experiments of
      xenon and ethylene demonstrate that the xenon atoms prefer to fill the greater
      pores of the material because the smaller pores are occupied with residual
      molecules from the synthesis procedure and additionally adsorbed ethylene.
      Besides the NMR experiments a series of electron paramagnetic resonance (EPR)
      measurements are performed to estimate the state of copper having a strong
      influence on the chemical shift of the adsorbed xenon. The EPR experiments
      demonstrate that spin exchange between the interconnected copper dimers is taking
      place across the BTC linker molecules in the Cu3(BTC)2 framework.

PMID- 17034194
TI  - Polymer-assisted growth of molybdenum oxide whiskers via a sonochemical process.
AB  - Whiskers of molybdenum oxides with high aspect ratios were synthesized from
      peroxomolybdate precursor solutions in the presence of small amounts of
      poly(ethylene glycol) (PEG) via a sonochemical process at temperatures of 25-70
      degrees C. Irradiation with ultrasound reduces the time needed for the growth of
      micrometer-sized whiskers from weeks to a few hours. The simplicity of the
      sonochemical approach also compares favorably to a hydrothermal/solvothermal
      process. The morphology, crystal structure, and other characteristics of the
      whiskers were characterized by scanning electron microscopy, transmission
      electron microscopy, selective area electron diffraction, energy-dispersive X-ray
      spectroscopy, wide-angle X-ray diffraction, Raman spectroscopy, thermogravimetric
      analysis, differential scanning calorimetry, and the Brunauer-Emmett-Teller
      method. The surface area of the calcified molybdenum oxide whiskers (55.4 m2/g)
      was found to be much higher than those of molybdenum oxide nanofibers (35 m2/g)
      or nanorods (13.4 m2/g) The growth rate of various crystal faces could be
      postulated to be controlled by the binding of peroxomolybdate ions to pseudo
      crown ether cavities formed by PEG. The reduction of molybdenum oxide to produce
      mixed-valent oxides and their growth could also be controlled by the reducing
      ability of PEG. The aspect ratio of the molybdenum oxide whiskers increased with
      decreasing concentration in the initial peroxomolybdate precursor solution.
      Whether the precursor solution species was H2Mo2O3(O2)4(H2O)2, H2MoO2(O2)2, or
      MoO2(OH)(OOH), the peroxide group in all the species disproportionates to give
      the final product MoO3 by a catalytic process. On the basis of experimental
      evidence of the dual role of glycols, a mechanism for the growth of the
      molybdenum oxide whiskers is proposed.

PMID- 17034195
TI  - Photoelectrochemistry of conducting polymers modified with electron-acceptor
      moieties.
AB  - The photoelectrochemical behavior of two polymers of the polythiophene series
      containing electron-acceptor groups in the main chain was studied and compared to
      that of the nonmodified polymer, poly(2,2'-bithiophene), PBT. The acceptor groups
      were 2,2'-bipyridine and biphenyl, which are electron-deficient as compared to
      the bithiophene unit. All three polymers demonstrated a pronounced photovoltaic
      effect, which for PBT was consistent with data reported earlier. The introduction
      of the electron-acceptor moieties was found to significantly enhance the
      magnitude of the steady-state photocurrent as well as to drastically alter the
      dependencies of the photocurrent on the polymer film thickness and the external
      bias. These observations indicated that the mechanism of photocurrent generation
      in the modified polymers differs from that in nonmodified polymer and involves
      the electron transfer to the electron-acceptor moieties in the polymer main
      chain. The values of the external quantum efficiency were estimated in a liquid
      cell arrangement to be 0.27 and 0.19% for modified and nonmodified polymers,
      respectively.

PMID- 17034196
TI  - Dendritic aggregation of oligothiophene during desorption of 2,5-diiodothiophene
      multilayer and topography-induced alignment of oligothiophene nanofibers.
AB  - The multilayer desorption behavior of 2,5-diidothiophene and the dendritic
      aggregation of photochemical reaction products during the desorption of 2,5
      diiodothiophene multilayers have been studied. Like many other aromatic
      compounds, 2,5-diiodothiophene shows a multilayer desorption behavior different
      from the typical zeroth-order kinetics, a metastable desorption peak growth at
      approximately 220 K followed by a thick multilayer peak growth at approximately
      235 K. Traditionally, these desorption behaviors have been attributed to the
      formation of three-dimensional clusters. This paper provides the direct evidence
      of this clustering process by producing nondesorbing photoreaction products in
      the multilayer and by imaging their clusters after the multilayer desorption.
      Oligothiophene species are produced via photochemical reactions of 2,5
      diiodothiophene during the multilayer deposition at approximately 180 K in
      ultrahigh vacuum (UHV). Upon heating the multilayer to room temperature, the
      oligothiophene species forms into fibrous aggregates with a fractal dimension
      varying from 1.37 to 1.81 depending on their surface concentration. Using a
      topographical alteration of the substrate with a repeating pattern, these
      oligothiophene fibers can be aligned to a certain direction. This may allow in
      situ fabrication of aligned conjugated polymer fibers directly on a target
      substrate.

PMID- 17034197
TI  - Synthesis of large-pore micelle-templated silico-aluminas at different alumina
      contents.
AB  - The EPR spectra of radical surfactant probes embedded in cetyltrimethylammonium
      bromide (CTAB) and trimethylbenzene (TMB) stable water emulsions (TMB/CTAB = 13)
      were analyzed to provide information on the kinetics of formation of micelle
      templated silicoaluminas (MTSA) at 343 K, obtained by means of silica and
      alumina, solved in alkaline solutions, at different Si/Al ratios. Textural
      (surface area, pore volume, pore size, surfactant content) and structural
      characterization of both as-synthesized and calcined MTSA were performed by means
      of nitrogen sorption isotherms, TEM, and chemical analysis. This analysis showed
      that TMB worked as a swelling agent of the CTAB micelles, providing large-pore
      homogeneous and stable MTSA at TMB/CTAB = 13 for Si/Al from infinity to 10. A
      demixing of the emulsion occurs at Si/Al < 10: at Si/Al = 7, a double wide-and
      narrow pore structure was formed; then, at Si/Al = 5, an amorphous material was
      obtained. At Si/Al > or = 10, the computer-aided analysis of the EPR spectra as a
      function of the synthesis time indicated the distribution of the probes in two
      different environments: "micellar" probes inserted in the surfactant aggregates,
      whose mobility decreases over the synthesis time, thus reporting on the
      progressive modification of the surfactant aggregates structure and the solid
      condensation, and "interacting" probes due to probe-surfactant heads
      electrostatically interacting with the charged surface sites induced by alumina
      incorporation in the silica network. This last fraction increases its relative
      amount over the synthesis time, informing about the condensation and
      structuration of the MTSA. Without alumina, the "interacting" component is absent
      in the EPR spectra because TMB preferentially interacts with the surfactant
      headgroups by cation-pi interactions, thus preventing the interactions of these
      headgroups with silanols. When alumina is added, the negatively charged
      silicoaluminate at the surface promotes the interaction of the ammonium
      headgroups with the surface, and some Na+ cations also interact with TMB by
      cation-pi interaction and contribute to decreasing the interaction of the
      headgroups with TMB. Therefore, increasing alumina contents promote electrostatic
      interactions between the positively charged surfactant heads and the negatively
      charged silicoaluminate groups. The strong interaction of the surfactants with
      the silicoaluminate surface allows the formation of a monolayerlike structure of
      surfactant, which is not observed in the absence of alumina. The synthesis is
      slowed by increasing alumina contents due to a destructuration effect of alumina
      in the MTSA formation.

PMID- 17034198
TI  - Efficient photocatalytic degradation of phenol over Co3O4/BiVO4 composite under
      visible light irradiation.
AB  - Co3O4/BiVO4 composite photocatalyst with a p-n heterojunction semiconductor
      structure has been synthesized by the impregnation method. The physical and
      photophysical properties of the composite photocatalyst have been characterized
      by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transimission
      electron microscopy (TEM), BET surface area, and UV-visible diffuse reflectance
      spectra. Co is present as p-type Co3O4 and disperses on the surface of n-type
      BiVO4 to constitute a heterojunction composite. The photocatalyst exhibits
      enhanced photocatalytic activity for phenol degradation under visible light
      irradiation. The highest efficiency is observed when calcined at 300 degrees C
      with 0.8 wt % cobalt content. On the basis of the calculated energy band
      positions and PL spectra, the mechanism of enhanced photocatalytic activity has
      been discussed.

PMID- 17034199
TI  - Giant reduction in dynamic modulus of kappa-carrageenan magnetic gels.
AB  - Effects of magnetization on the complex modulus of kappa-carrageenan magnetic
      gels have been investigated. The magnetic gel was made of a natural polymer,
      kappa-carrageenan, and a ferrimagnetic particle, barium ferrite. The complex
      modulus was measured before and after magnetization of the gel by dynamic
      viscoelastic measurements with a compressional strain. The gels showed a giant
      reduction in the storage modulus of approximately 10(7) Pa and also in the loss
      modulus of approximately 10(6) Pa due to magnetization. The reduction increased
      with increasing volume fraction of ferrite, and it was nearly independent of the
      frequency. It was also found that the change in the modulus was nearly
      independent of the magnetization direction and irradiation time of the magnetic
      fields to the gel. The magnetic gels demonstrating the giant reduction in the
      dynamic modulus showed a large nonlinear viscoelastic response. It was observed
      that the magnetic gel was deformed slightly due to magnetization. The observed
      giant complex modulus reduction could be attributed to the nonlinear
      viscoelasticity and deformation caused by magnetization. Magnetism, nonlinear
      viscoelasticity, and effects of magnetization on the morphological and shape
      changes were discussed.

PMID- 17034200
TI  - Viscoelastic micellar solutions in nonionic fluorinated surfactant systems.
AB  - The formation and rheological behavior of a viscoelastic wormlike micellar
      solution in an aqueous solution of a nonionic fluorinated surfactant,
      perfluoroalkyl sulfonamide ethoxylate, of structure C8F17SO2N(C3H7)(CH2CH2O)10H
      was studied. Temperature-induced viscosity growth is observed even at low
      surfactant concentration (approximately 1 wt %), and viscosity reaches the
      maximum at a temperature T(eta)-max. Upon successive increases in the
      temperature, the viscosity decreases, and ultimately a phase separation occurs.
      Small-angle X-ray scattering (SAXS) measurements confirm the presence of
      cylindrical aggregates at low temperature, which undergo continuous one
      dimensional growth with increasing temperature, and ultimately, an indication of
      a slight lamellarlike structural pattern is observed, which probably comes from
      the formation of micellar joints or branching. Such changes in the microstructure
      result in a decrease in the viscosity and stress-relaxation time, while the
      network structure is retained; the trends in the evolution of shear modulus (Go)
      and relaxation time (tauR) with temperature are in agreement with this. With
      increased surfactant concentration, the temperature corresponding to the
      viscosity maximum (T eta-max) in the temperature-viscosity curve shifts to lower
      values, and the viscosity at temperatures below or around T eta-max increases
      sharply. A viscoelastic solution with Maxwellian-type dynamic rheological
      behavior at low-shear frequency is formed, which is typical of entangled wormlike
      micelles. Rheological parameters, eta(o) and Go, show scaling relationships with
      the surfactant concentrations with exponents slightly greater than the values
      predicted by the living-polymer model, but the exponent of tauR is in agreement
      with the theory. Dynamic light-scattering measurements indicate the presence of
      fast relaxation modes, associated with micelles, and medium and slow modes,
      associated with transient networks. The disappearance of the slow mode and the
      predominance of the medium mode as the temperature increases support the
      conclusions derived from SAXS and rheometry.

PMID- 17034201
TI  - Structural characteristics of a 0.23 mole fraction aqueous solution of
      tetrahydrofuran at 20 degrees C.
AB  - Hydrogen/deuterium isotopic substitution neutron diffraction techniques were used
      to measure the structural correlation functions in a 0.23 mole fraction solution
      of tetrahydrofuran in water at room temperature. Empirical potential structure
      refinement (EPSR) was used to build a three-dimensional model of the liquid
      structure that is consistent with the experimental data. Detailed analysis shows
      a preference for nonpolar interactions between the cyclic ether molecules plus
      polar interactions between the ether and solvent water and hydrophobic hydration
      of the nonpolar regions of the solute. The increase in the number of hydrogen
      bond-acceptor sites relative to the number of hydrogen-bond-donor sites in this
      system, compared to the balanced situation that would be found in pure water, has
      a marked compressive effect on the structure of the solvent. Despite the small
      size of the solvent water molecules, the 0.23 mole fraction aqueous solution is
      still found to contain small voids akin to those in pure liquid tetrahydrofuran.
      In contrast to the positive surface charge of the voids in the pure system, the
      average void in this aqueous solution is found to have a net negative charge.
      This is due to contributions from the water oxygen atoms that are negatively
      polarized by their intramolecular bonding.

PMID- 17034202
TI  - Balance of hydrophobic and electrostatic forces in the pH response of weak
      polyelectrolyte capsules.
AB  - A detailed study of the role of solution pH and ionic strength on the swelling
      behavior of capsules composed of the weak polyelectrolytes poly(4-vinylpyridine)
      (P4VP) and poly(methacrylic acid) (PMA) with different numbers of layers was
      carried out. The polyelectrolyte layers were assembled onto silicon oxide
      particles and multilayer formation was followed by zeta-potential measurements.
      Hollow capsules were investigated by scanning electron microscopy and atomic
      force microscopy. The pH-dependent behavior of P4VP/PMA capsules was probed in
      aqueous media using confocal laser scanning microscopy. All systems exhibited a
      pronounced swelling at the edges of stability, at pHs of 2 and 8.1. The swelling
      degree increased when more polymer material was adsorbed. The swollen state can
      be attributed to uncompensated positive and negative charges within the
      multilayers, and it is stabilized by counteracting hydrophobic interactions. The
      swelling was related to the electrostatic interactions by infrared spectroscopy
      and zeta-potential measurements. The stability of the capsules as well as the
      swelling degree at a given pH could be tuned, when the ionic strength of the
      medium was altered.

PMID- 17034203
TI  - Controlling the diameter of carbon nanotubes in chemical vapor deposition method
      by carbon feeding.
AB  - It was found that the diameter distribution of single-walled carbon nanotubes
      (SWNTs) grown by the chemical vapor deposition (CVD) method could be controlled
      by the carbon feeding rate at the growth stage. A unified hypothesis on the
      relationship between nanoparticle size, growth condition, growth temperature, and
      diameter of the resulting nanotubes was developed and used to explain the
      relationship. It was shown that the diameters of SWNTs can be controlled even
      when highly polydisperse nanoparticles were used as catalyst. Such control
      enabled us to synthesize uniform small-diameter SWNTs at low carbon feeding
      rates. Additionally, understanding of the important role of the carbon feeding
      rate can be used to explain the cause of low growth efficiency in most CVD
      processes. It would also help us to design methods to improve the growth
      efficiency of CVD growth of nanotubes.

PMID- 17034204
TI  - Electron transfer in multiply bridged donor-acceptor molecules: Dephasing and
      quantum coherence.
AB  - We present a simple theoretical treatment of nonadiabatic electron transfer in
      multiply bridged donor-bridge-acceptor molecules using the density matrix
      formalism. Destructive interference can result from different signed couplings
      between bridge sites, with the simplest system being a four-site Joachim-type
      molecular interferometer. Previous work has shown that deposition of energy on
      the bridge sites erases the interference and recovers transport. We show that
      pure local dephasing, a completely elastic process, is also capable of
      eliminating destructive interference and regaining transport. Destructive
      interference as a result of system connectivity can explain the familiar ortho
      meta-para reactivity of benzene bridges. We also show that pure dephasing can
      yield a coalescence of ortho, meta, and para effective coupling strengths and
      suggest a system to observe this effect experimentally.

PMID- 17034205
TI  - Growth of ZnO nanostructures with different morphologies by using hydrothermal
      technique.
AB  - ZnO nanostructures, including nanotowers, nanovolcanoes, nanorods, nanotubes, and
      nanoflowers, have been grown by using the hydrothermal technique. Most of the ZnO
      nanostructures show the perfect hexagonal cross section and well-faceted top and
      side surfaces. The basic chemistry and growth mechanism are discussed. By
      increasing the reaction time, the volcano-like and tube-like ZnO structures were
      formed due to the Ostwald ripening process and the selective adsorption of the
      complexes. By using the seed layer, the dense-arrayed, regular oriented ZnO
      nanorods were obtained due to the decreased nucleation barrier and the abundant
      interfaces as well as the increasing surface roughness.

PMID- 17034206
TI  - Temperature-dependent relaxation of excitons in tubular molecular aggregates:
      Fluorescence decay and stokes shift.
AB  - We report temperature-dependent steady-state and time-resolved fluorescence
      studies to probe the exciton dynamics in double-wall tubular J-aggregates formed
      by self-assembly of the dye 3,3'-bis(3-sulfopropyl)-5,5',6,6'-tetrachloro-1,1'
      dioctylbenzimidacarbocyanine. We focus on the lowest energy fluorescence band,
      originating from the inner cylindrical wall. At low temperatures, the experiments
      reveal a nonexponential decay of the fluorescence, with a typical time scale that
      depends on the emission wavelength. At these temperatures we also find a dynamic
      Stokes shift of the fluorescence spectrum and its nonmonotonic dependence on
      temperature under steady-state conditions. All these data indicate that below
      about 20 K the excitons in the lowest fluorescence band do not reach thermal
      equilibrium before emission occurs, while above about 60 K thermalization on this
      time scale is complete. By comparing the two lowest fluorescence bands, we also
      find indications for fast energy transfer from the outer to the inner wall. We
      show that the Frenkel exciton model with diagonal disorder, which previously has
      been proposed to explain the absorption and linear dichroism spectra of these
      aggregates, yields a quantitative explanation to the observed dynamics. To this
      end, we extend the model to account for weak phonon-induced scattering of the
      localized exciton states; the spectral dynamics are then described by solving a
      Pauli master equation for the exciton populations.

PMID- 17034207
TI  - Judd-Ofelt intensity parameters and spectral properties of Gd2O3:Eu3+
      nanocrystals.
AB  - Three nonequivalent centers of Cs (A, B, and C) in monoclinic phase and C2 and S6
      centers in cubic phase were identified in the Gd2O3:Eu3+ nanocrystals with
      spectral techniques. Size dependence in the spectra indicated that the
      excitations from both host and charge-transfer band (CTB) for the 5D0 --> 7F2
      transition of Eu3+ ions were nearly equal for a larger size of 135 nm of the
      cubic phase; however, with decreasing the size to or less than 23 nm, the
      excitations by the CTB dominated. The variation of excitation leading to the
      symmetry and energy change in the C2 and S6 sites was also observed for larger
      particle sizes. The Judd-Ofelt intensity parameters Omega(lambda) (lambda = 2, 4)
      for Gd2O3:Eu3+ nanoparticles were experimentally determined. The parameters
      Omega(lambda) were found to significantly change with the sizes of Gd2O3:Eu3+
      from nanoparticles to bulk material. With decreasing the size from 135 to 15 nm,
      the quantum efficiencies for 5D0 reduced from 23.6% to 4.6% due to the increasing
      ratio of surface to volume.

PMID- 17034208
TI  - NIR luminescence intensities increase linearly with proportion of polar thiolate
      ligands in protecting monolayers of Au38 and Au140 quantum dots.
AB  - The near-infrared photoluminescence of monolayer-protected Au38 and Au140
      clusters (MPCs) is intensified with exchange of nonpolar ligands by more polar
      thiolate ligands. The effect is general and includes as more polar in-coming
      ligands: thiophenolates with a variety of p-substituents; alkanethiolates omega
      terminated by alcohol, acid, or quaternary ammonium groups; and thio-amino acids.
      Remarkably, place exchanges of the initial phenylethanethiolates on Au38 MPCs by
      p-substituted thiophenolates and thio-amino acids and of hexanethiolates on Au140
      MPCs by omega-quaternary ammonium terminated undecylthiolates result in increases
      in the near-infrared (NIR) luminescence intensities that are linear with the
      number of new polar ligands. The increased intensities are systematically larger
      for thiophenolate ligands having more electron-withdrawing substituents.
      Analogous effects on intensities are observed in the NIR emission of Au140 MPCs
      upon place exchange of alkanethiolates with thiolates having short connecting
      alkanethiolate chains to quaternary ammonium and to omega-carboxylic acid
      termini, and with oxidative charging of the Au cores. The observations are
      consistent with sensitivity of the luminescence mechanism to any factor that
      enhances the electronic polarization of the bonds between the Au core atoms and
      their thiolate ligands. The luminescence is discussed in terms of a surface
      electronic excitation, as opposed to a core volume excitation.

PMID- 17034209
TI  - A tight-binding method for predicting magnetic ordering in Gd-containing solids:
      Application to GdB2C2.
AB  - Herein we present a method to compute d-f mediated exchange coupling in Gd
      containing systems with a spin-dependent extended Huckel-tight binding (EHTB)
      method. EHTB parameters were chosen to exactly reproduce the spin density
      functional calculation (SDFT) energy gap of the S = 45/2 and 39/2 spin patterns
      for a model compound, Gd6CoI12(OPH3)6. Comparison between SDFT and EHTB results
      shows a good match between the spin-pattern energy distribution for the two
      methods. We applied our EHTB method to the solid-state compound GdB2C2 by
      considering 6 different variations in the ordering of the 4f7 moments.
      Calculations indicate that this metallic system should exhibit antiferromagnetic
      ordering of the 4f7 moments with a magnetic structure consistent with published
      neutron diffraction results.

PMID- 17034210
TI  - Pulsating pH-responsive nanogels.
AB  - A novel method is presented for the design of robust, sustained
      nanochemomechanical oscillators. The approach is based on the switching of
      chemoresponsive nanogel beads between their collapsed and swollen state by
      coupling them to an appropriately chosen nonlinear reaction. The presented system
      utilizes a proton activated oscillatory reaction and pH-sensitive nanobeads of
      gel that provide more than an order of magnitude volume change. A key point of
      our approach is the control of the colloid stability of the nanobeads of gel in a
      wide range of experimental parameters (pH, ionic strength, temperature) without
      interfering with the swelling characteristics of the nanogel particles. This was
      achieved by utilizing the interaction of nanogels with ionic surfactants.

PMID- 17034211
TI  - Enhanced electrical percolation due to interconnection of three-dimensional
      pentacene islands in thin films on low surface energy polyimide gate dielectrics.
AB  - The role of lateral interconnections between three-dimensional pentacene islands
      on low surface energy polyimide gate dielectrics was investigated by the
      measurement of the surface coverage dependence of the charge mobility and the use
      of conducting-probe atomic force microscopy (CP-AFM). From the correlation
      between the electrical characteristics and the morphological evolution of the
      three-dimensionally grown pentacene films-based field-effect transistors, we
      found that during film growth, the formation of interconnections between the
      three-dimensional pentacene islands that are isolated at the early stage
      contributes significantly to the enhancement process of charge mobility. The CP
      AFM current mapping images of the pentacene films also indicate that the lateral
      interconnections play an important role in the formation of good electrical
      percolation pathways between the three-dimensional pentacene islands.

PMID- 17034212
TI  - Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic
      quantum dots.
AB  - Luminescent semiconductor quantum dots (QDs) have great potential for use in
      biological assays and imaging. These nanocrystals are capped with surface ligands
      (bifunctional molecules, amphiphilic polymers, phospholipids, etc.) that render
      them hydrophilic and provide them with functional properties. These coatings
      alters their hydrodynamic radii and surface charge, which can drastically affect
      properties such as diffusion within the cell cytoplasm. Heavy atom techniques
      such as transmission electron microscopy and X-ray scattering probe the inorganic
      core and do not take into account the ligand coating. Herein we use dynamic light
      scattering to characterize the hydrodynamic radius (R(H)) of CdSe-ZnS QDs capped
      with various hydrophilic surface coatings (including dihydrolipoic acid and
      amphiphilic polymers) and self-assembled QD-protein bioconjugates. Experiments
      were complemented with measurements of the geometric size and zeta potential
      using agarose gel electrophoresis and laser Doppler velocimetry. We find that the
      effects of surface ligands on the hydrodynamic radius and on the nanoparticle
      mobility are complex and strongly depend on a combination of the inorganic core
      size and nature and lateral extension of the hydrophilic surface coating. These
      properties are critical for the design of QD-based biosensing assays as well as
      QD bioconjugate diffusion in live cells.

PMID- 17034213
TI  - Synthesis and photophysical characteristics of 2,7-fluorenevinylene-based trimers
      and their electroluminescence.
AB  - Three new 2,7-fluorenevinylene-based trimers were synthesized and characterized.
      The synthesis was carried out by the Heck coupling reaction of 9,9-dihexyl-2,7
      divinylfluorene with 2-(4-bromophenyl)-5-phenyl-1,3,4-oxadiazole, N,N-diphenyl-4
      bromoaniline, or 3-bromopyrene to afford the trimers OXD, TPA, and PYR,
      respectively. All the trimers were readily soluble in common organic solvents
      such as tetrahydrofuran, dichloromethane, chloroform, and toluene. Their glass
      transition temperatures ranged from 33 to 60 degrees C. The UV-vis spectra showed
      an absorption maximum at lambda(a,max) = 379-417 nm with optical band gap of Eg =
      2.47-2.66 eV. In solution, they emitted strong blue-green photoluminescence (PL)
      with PL maximum at lambda(f,max) = 455-565 nm and fluorescence quantum yield of
      Phi(f) = 0.65-0.74. On the other hand, in their spin-coated films, the PL
      efficiencies significantly decreased due to the presence of concentration
      quenching. All samples showed nanosecond transient lifetime containing two
      components, suggesting excimer formation. The organic light-emitting diodes
      (OLEDs) with OXD and TPA showed green emission with electroluminescence (EL)
      quantum efficiencies of eta(EL) approximately 10(-2)%, while very weak EL
      efficiency of eta(EL) approximately 10(-5)% was observed with PYR. The highest
      occupied molecular orbital (HOMO) levels of the films were found to be 5.05-5.75
      eV.

PMID- 17034214
TI  - Kinetic prediction of functional group distributions in thermosensitive
      microgels.
AB  - A kinetic model accounting for the copolymerization of up to four comonomers is
      applied to predict both chain and radial functional group distributions in
      carboxylic-acid-functionalized poly(N-isopropylacrylamide) (NIPAM)-based
      microgels. The model can accurately predict the experimentally observed radial
      distributions of functional monomers in microgels prepared using a variety of
      different carboxylic-acid-functionalized monomers with significantly different
      hydrophobicities, copolymerization kinetics, and reactivities, without requiring
      the use of adjustable parameters. Multimodal distributions can both be predicted
      and experimentally generated by copolymerizing two -COOH-containing monomers with
      widely different reactivities. Chain distributions and monomer block formation
      can also be probed using the kinetic model, allowing for qualitative predictions
      of the potentiometric titration behavior of the microgels. The kinetic model
      reported herein therefore provides the first available analytical method for
      semiquantitatively predicting and controlling functional group distributions in
      bulk-polymerized microgel systems.

PMID- 17034215
TI  - Reactivity of molecularly chemisorbed oxygen on a Au/TiO2 model catalyst.
AB  - We present results of an investigation into the reactivity of molecularly
      chemisorbed oxygen with CO on a Au/TiO2 model catalyst at 77 K. We previously
      discovered that exposing the model catalyst sample to a radio-frequency-generated
      plasma jet of oxygen results in co-population of both atomically and molecularly
      chemisorbed oxygen species on the sample. We tested the reactivity of the
      molecularly chemisorbed oxygen by comparing the CO2 produced from a sample
      populated with both species to the CO2 produced from a sample that has been
      cleared of molecularly chemisorbed oxygen employing collision-induced desorption.
      Samples that are populated with both species consistently result in greater CO2
      produced than samples with only atomic oxygen. We interpret this result to
      indicate that molecularly chemisorbed oxygen on the sample can directly
      participate in the CO oxidation reaction. The reactivity of molecularly
      chemisorbed oxygen has been investigated for five different gold coverages (0.5,
      0.75, 1, 1.25, and 2 ML), and we observe that there is a greater fractional
      difference in the CO2 produced (difference between sample populated with both
      molecularly and atomically adsorbed oxygen and sample populated solely with
      atomically adsorbed oxygen) for the 1 ML Au coverage than for the other coverages
      for equivalent oxygen plasma-jet exposures. However, it is not possible to
      unambiguously conclude that this observation is directly related to a particle
      size effect on the chemistry since the absolute O(2,a) and O(a) content on the
      various surfaces is different for all the coverages studied because of the plasma
      jet technique that we employed for populating the surfaces with oxygen.
      Unfortunately, this precludes a direct comparison of the reactivity of molecular
      oxygen in the carbon monoxide oxidation reaction as a function of gold coverage
      and hence particle size.

PMID- 17034216
TI  - Single molecule observations of the adsorption sites of methyl isocyanide on
      Pt(111) by low-temperature scanning tunneling microscopy.
AB  - Scanning tunneling microscopy (STM) has been used to directly investigate the
      local structure of methyl isocyanide (CNCH3) adsorbed on Pt(111). At low
      coverages, CNCH3 is preferentially adsorbed at on-top sites, in agreement with
      earlier deductions based on vibrational spectroscopy. When dosed at low coverages
      at 50 K, the molecules tend to adsorb near other CNCH3 molecules with preferred
      distances of a and a, where a = 2.78 A is the lattice constant of Pt. Annealing
      the surface to 120 K, however, results in a more uniform separation of the
      molecules. At higher coverages, the CNCH3 molecules are observed to occupy both
      on-top and two-fold bridge sites. On the basis of STM image analysis, CNCH3 forms
      an ordered layer of (2 x 3) periodicity at 0.33 ML. Additional details on the
      structures of CNCH3 adsorbed at the on-top and two-fold bridge sites are provided
      by density functional theory (DFT) calculations. At a coverage that saturates the
      first layer (0.33 ML), the occupation ratio for the on-top and two-fold bridge
      bonded CNCH3 is 1:1, which is consistent with the results obtained from the
      combined use of experimental reflection absorption infrared spectroscopy (RAIRS)
      data and DFT calculations.

PMID- 17034217
TI  - The impact of the layer thickness on the thermodynamic properties of pd hydride
      thin film electrodes.
AB  - Recently, a lattice gas model was presented and successfully applied to simulate
      the absorption/desorption isotherms of various hydride-forming materials. The
      simulation results are expressed by parameters corresponding to several energy
      contributions, e.g., interaction energies. However, the use of a model system is
      indispensable in order to show the strength of the simulations. The palladium
      hydrogen system is one of the most thoroughly described metal hydrides found in
      the literature and is therefore ideal for this purpose. The effects of decreasing
      the thickness of Pd thin films on the isotherms have been monitored
      experimentally and subsequently simulated. An excellent fit of the lattice gas
      model to the experimental data is found, and the corresponding parameters are
      used to describe several thermodynamic properties. It is analyzed that the
      contribution of H-H interaction energies to the total energy and the influence of
      the host lattice energy are significantly and systematically changing as a
      function of Pd thickness. Conclusively, it has been verified that the lattice gas
      model is a useful tool to analyze thermodynamic properties of hydrogen storage
      materials.

PMID- 17034218
TI  - External electric field effects on absorption and fluorescence spectra of a
      fullerene derivative and its mixture with zinc-tetraphenylporphyrin doped in a
      PMMA film.
AB  - Electroabsorption and electrofluorescence spectra of a fullerene derivative,
      C60(C18)2, and its mixture with zinc-tetraphenylporphyrin (ZnTPP) have been
      measured by using electric field modulation spectroscopy. The change in dipole
      moment is significant in the electroabsorption spectra both of C60(C18)2 and of a
      complex composed of C60(C18)2 and ZnTPP, indicating that the excited states both
      of C60(C18)2 and of a complex between C60(C18)2 and ZnTPP have a large charge
      transfer character. The fluorescence quantum yield of C60(C18)2 decreases in the
      presence of an electric field, which probably arises from the field-induced
      acceleration of the intramolecular nonradiative process of C60(C18)2 in the
      fluorescent state. In a mixture between ZnTPP and C60(C18)2, electrofluorescence
      spectra show the field-induced enhancement for the fluorescence of ZnTPP and the
      field-induced de-enhancement for the fluorescence both of C60(C18)2 and of the
      complex between ZnTPP and C60(C18)2. A theoretical analysis clearly shows that
      the field-induced enhancement of the ZnTPP fluorescence in a mixture results from
      the field-induced deceleration of the rate of the electron transfer from the
      excited ZnTPP to C60(C18)2. The standard free energy gap for the photoinduced
      electron-transfer process is estimated based on the theoretical simulation of the
      field-dependent fluorescence intensity.

PMID- 17034219
TI  - Seed-mediated growth of palladium nanocrystals on indium tin oxide surfaces and
      their applicability as modified electrodes.
AB  - Palladium nanoparticles (PdNPs) were successfully attached and grown on an indium
      tin oxide (ITO) surface using a seed-mediated growth method, i.e., via a simple
      two-step immersion of the ITO substrate into the seed and growth solutions. After
      the growth treatment for 24 h, PdNPs grew up to 60-80 nm, exhibiting crystal-like
      appearances and accompanying the formation of short rodlike nanocrystals as a
      minor product. Thus prepared PdNPs tend to stick each other, so that the dense
      gathering of PdNPs was observed on the ITO surfaces. Due to the dense attachment,
      the PdNPs directly attached to the ITO (PdNP/ITO) electrode had a significantly
      lowered charge-transfer resistivity compared with that of a bare ITO, and the
      redox reaction of [Fe(CN)6]3-/[Fe(CN)6]4- was observed as reversible in 0.1 M
      phosphate buffer solution. The electrocatalytic property of PdNPs was confirmed
      for the reduction of oxygen. In addition, some typical responses were observed in
      0.5 M H2SO4 with the PdNP/ITO electrode, reflecting both the characteristics of
      NPs and the thin layer in nanoscale. The present preparation method of PdNP
      attached surfaces would be promising for catalytic applications as well as
      electrochemical uses.

PMID- 17034220
TI  - Alkaline treatment of iron-containing MFI zeolites. Influence on mesoporosity
      development and iron speciation.
AB  - The effects of alkaline treatment on the mesoporosity development and iron
      speciation in Fe-MFI zeolites have been investigated. To this end, a variety of
      samples derived from different synthetic routes and having distinct Si/Al ratios
      and Fe content were treated in NaOH solutions and characterized by N2 adsorption,
      SEM, TEM, UV/vis spectroscopy, and EPR. The alkaline treatment induces a
      significant intracrystalline mesoporosity development by framework silicon
      extraction and promotes disintegration of oligomeric iron species. Iron in
      framework positions has shown to provoke mesopore formation, whereas nonframework
      iron species suppresses silicon leaching and lowers the extent of extra porosity.

PMID- 17034221
TI  - Surface-enhanced Raman scattering at the silver electrode/ionic liquid (BMIPF6)
      interface.
AB  - This is the first report of in situ SER spectra of chemical species adsorbed on a
      Ag/room temperature ionic liquid (RTIL) interface. We have investigated the
      dependence of the SERS intensity of the RTIL derived from 1-n-butyl-3
      methylimidazolium hexafluorophosfate (BMIPF6) adsorbed on a silver electrode. It
      has been shown that the BMI+ adsorbs on the silver electrode for potentials more
      negative than -0.4 V vs a Pt quasireference electrode (PQRE). In the -0.4 to -1.0
      V potential range the SER spectra are similar to the Raman spectrum of the RTIL
      BMIPF6. At potentials more negative than -1.0 V some imidazolium ring vibrational
      modes and N-CH3 vibrations are enhanced, suggesting that the imidazolium ring is
      parallel to the surface and for potentials <-2.8 V the BMI+ is reduced to the BMI
      carbene. The potential dependence of the SERS intensities of Py adsorbed on a
      silver electrode in BMIPF6 has also been investigated. The results have shown
      that at potentials less negative than -0.8 V (vs PQRE) Py adsorbs at an end-on
      configuration forming an Ag-N bond. In the -0.9 to -1.4 V potential range Py
      molecules lie flat on the electrode surface and at potentials <-1.4 V Py is
      replaced by the BMI+. The electrochemical and SERS results have shown that Py has
      the effect of changing the oxidation of silver in that medium as well as the
      reduction of BMI+ to the BMI carbene. In the presence of Py the BMI+ reduction is
      observed at potentials near -2.4 V. The Ag electrode has presented SERS activity
      from 0.0 to -3.0 V.

PMID- 17034222
TI  - Electrochemically partitioned assembly of organosulfur monolayers and
      nanoparticles.
AB  - Partitionally assembled organosulfur monolayers were prepared by using an
      electrochemically assisted assembly method on gold films that were preseparated
      into two regions insulated from each other. Cyclic voltammetry (CV) and X-ray
      photoelectron spectroscopy (XPS) were employed to characterize the n
      dodecanethiol (DDT) and the 11-mercaptoundecanoic acid (MUA) monolayers, which
      were separately assembled on different substrate regions. CV results indicated
      that both the DDT- and MUA-coated gold electrodes showed a blocking property
      toward the negatively charged redox probe Fe(CN)6(3-). However, when positively
      charged Ru(NH3)6(3+) was used as the redox probe, the MUA- and DDT-modified
      electrodes showed quasireversible and blocking CV features, respectively. These
      phenomena were attributed to different interactions between the negatively
      charged MUA surface and the negatively or positively charged redox probes. XPS
      spectra obtained on the MUA modified region exhibited an O(1s) peak and a small
      discrete C(1s) peak, which arose from the oxygen and the carbon atoms in the
      carboxylic acid groups, respectively. For the DDT-modified region, these two
      peaks were absent. CV and XPS experimental results provided strong evidence that
      different SAMs were selectively deposited onto different regions of the
      preexisting patterns of the substrate by electrochemically partitioned assembly.
      The partitionally assembled sulfur-based monolayers with different terminal
      groups were used to form location-selective nanoparticle assemblies. This
      electrochemically partitioned assembly technique has great potential in
      controllable constructions of molecular layers and nanostructures on different
      surface microarchitectures that are closely integrated on one substrate but
      insulated from each other.

PMID- 17034223
TI  - Solvent effects on AOT reverse micelles in liquid and compressed alkanes
      investigated by neutron spin-echo spectroscopy.
AB  - Neutron Spin-Echo (NSE) spectroscopy has been employed to study the interfacial
      properties of reverse micelles formed with the common surfactant sodium bis-2
      ethylhexyl-sulfosuccinate (AOT) in liquid alkane solvents and compressed propane.
      NSE spectroscopy provides a means to measure small energy transfers for incident
      neutrons that correspond to thermal fluctuations on the nanosecond time scale and
      has been applied to the study of colloidal systems. NSE offers the unique ability
      to perform dynamic measurements of thermally induced shape fluctuation in the AOT
      surfactant monolayer. This study investigates the effects of the bulk solvent
      properties, water content, and the addition of octanol cosurfactant on the
      bending elasticity of AOT reverse micelles and the reverse micelle dynamics. By
      altering these solvent properties, specific trends in the bending elasticity
      constant, k, are observed where increasing k corresponds to an increase in
      micelle rigidity and a decrease in intermicellar exchange rate, k(ex). The
      observed corresponding trends in k and k(ex) are significant in relating the
      dynamics of microemulsions and their application as a reaction media. Compressed
      propane was also examined for the first time with a high-pressure, compressible
      bulk solvent where variations in temperature and pressure are used to tune the
      properties of the bulk phase. A decrease in the bending elasticity is observed
      for the d-propane/AOT/W = 8 reverse micelle system by simultaneously increasing
      the temperature and pressure, maintaining constant density. With isopycnic
      conditions, a constant translational diffusion of the reverse micelles through
      the bulk phase is observed, conforming to the Stokes-Einstein relationship.

PMID- 17034224
TI  - Dynamic and collective electrochemical responses of tetrathiafulvalene derivative
      self-assembled monolayers.
AB  - Electroactive tetrathiafulvalene (TTF)-containing alkanethiol self-assembled
      monolayers (SAMs) were designed and synthesized to elucidate the relationship
      between electrochemical responses and film structures. Two TTF derivative
      molecules having one alkanethiol chain (1) and two alkanethiol chains (2) were
      utilized to modulate the molecular packing arrangements in the SAMs, and the
      formation and structure of the SAMs were characterized by surface plasmon
      resonance spectroscopy (SPR). SPR measurements in various contacting media
      demonstrated loose packing of SAM 1 and close packing of SAM 2 due to the
      different space fillings of the molecules. Two successive one-electron redox
      waves were observed for both SAMs by cyclic voltammetry. The peak widths of the
      redox waves were strongly dependent on the oxidation states of the TTF moieties,
      the packing arrangement of the SAMs, and the contacting medium. We found that TTF
      based SAMs exhibited collective electrochemical responses induced by dynamic
      structural changes, depending on the degree of freedom for the component
      molecules in the SAMs. These results imply that the molecular design, taking into
      account the electrochemical responses, extends the available range of molecular
      based functionalities in TTF-based SAMs.

PMID- 17034225
TI  - Sr(II) in water: A labile hydrate with a highly mobile structure.
AB  - Despite the large number of experimental as well as theoretical investigations
      available in the literature, some properties of the hydration structure of
      Sr(II), for example, the coordination number, are still ambiguous. The presented
      molecular dynamics study based on a most suitable ab initio QM/MM protocol
      allowed a detailed investigation of structural and dynamical properties of this
      hydrate, which shows a considerable degree of internal flexebility as well as
      ligand mobility within the first shell. Despite the high computational effort an
      exceptionally long QM/MM simulation had to be carried out to obtain sufficient
      information to investigate first shell ligand exchange reactions.

PMID- 17034226
TI  - Structure and identity of 4,4'-thiobisbenzenethiol self-assembled monolayers.
AB  - Self-assembled monolayers (SAMs) of 4,4'-thiobisbenzenethiol (TBBT) can be formed
      on Au surface spontaneously. The structural characteristics and adsorption
      behavior of TBBT SAMs on Au have been investigated by surface enhanced Raman
      scattering (SERS), electrochemical cyclic voltammetry (CV), ac impedance
      spectroscopy (EIS), and atomic force microscopy (AFM). It is demonstrated that
      TBBT adsorbed on Au by losing a H atom, forming one Au-S bond, and the other
      mercapto group is free at the surface of the monolayer owing to the presence of
      the nu(S-H) at 2513 cm(-1) and the delta(C-S-H) at 910 cm(-1) in SERS. The
      enhancement of the vibration of C-S (1064 cm(-1)), the aromatic C-H vibration
      (3044 cm(-1)), and the absence of the vibration of S-S illustrate TBBT adsorbed
      on Au forming a monolayer with one benzene ring tilted with respect to the Au
      surface. The interpretation of the observed frequencies is aided by ab initio
      molecular orbital (MO) calculations at the HF/6-31G level of theory.
      Electrochemical CV and EIS indicate TBBT monolayers can passivate the Au
      effectively for its low ratio of pinhole defects (theta = 99.6%). AFM studies
      give details about the surface morphology. The applications of TBBT SAMs have
      been extensively investigated by exposure of Cu2+ ion to TBBT SAMs on Au and
      covalent adsorption of metal nanoparticles. Electrochemical, X-ray photoelectron
      spectroscopic, and SERS results indicate that Cu2+ can react with TBBT SAMs and
      present on TBBT SAMs as Cu(I). A scanning electron microscopic image of Ag
      nanoparticles on TBBT/Au and the Raman spectrum of TBBT in smooth macroscopic
      Au/TBBT SAMs/Ag nanoparticle sandwich structure indicate that metal nanoparticles
      can be adsorbed on TBBT SAMs effectively through covalent linkage.

PMID- 17034227
TI  - Infrared spectroscopic investigation of the reaction of hydrogen-terminated,
      (111)-oriented, silicon surfaces with liquid methanol.
AB  - Fourier transform infrared spectroscopy and first principles calculations have
      been used to investigate the reaction of atomically smooth, hydrogen-terminated
      Si(111) (H-Si) surfaces with anhydrous liquid methanol. After 10 min of reaction
      at room temperature, a sharp absorbance feature was apparent at approximately
      1080 cm(-1) that was polarized normal to the surface plane. Previous reports have
      identified this mode as a Si-O-C stretch; however, the first principles
      calculations, presented in this work, indicate that this mode is a combination of
      an O-C stretch with a CH3 rock. At longer reaction times, the intensity of the Si
      H stretching mode decreased, while peaks attributable to the O-C coupled stretch
      and the CH3 stretching modes, respectively, increased in intensity. Spectra of H
      Si(111) surfaces that had reacted with CD3OD showed the appearance of Si-D
      signals polarized normal to the surface as well as the appearance of vibrations
      indicative of Si-OCD3 surface species. The data are consistent with two surface
      reactions occurring in parallel, involving (a) chemical attack of hydrogen
      terminated Si(111) terraces by CH3OH, forming Si-OCH3 moieties having their Si-O
      bond oriented normal to the Si(111) surface and (b) transfer of the acidic
      hydrogen of the methanol to the silicon surface, either through a direct H-to-D
      exchange mechanism or through a mechanism involving chemical step-flow etching of
      Si-H step sites.

PMID- 17034228
TI  - Effect of model potential of adsorptive bond on the thermodynamic properties of
      adsorbed CO molecules on Ni(111) surface.
AB  - The effect of anharmonicity on the adsorption of CO molecules on the Ni(111)
      surface has been investigated. The DFT calculations are used to obtain the
      effective adsorption potential of the CO molecule on the Ni(111) surface. First,
      using an appropriate slab model, the geometry of adsorption system corresponding
      to hcp, fcc, bridge, and on-top sites with p(2 x 2) arrangement and coverage of
      0.25 ML is optimized by the DFT calculations using a plane wave basis set and
      ultrasoft pseudopotentials; this gives the hcp site as the most stable site with
      De = 185 kJ/mol, for which the equilibrium distance of CO from the surface and C
      O bond length on the surface are found to be 1.31 and 1.192 A, respectively.
      Then, the potential function of adsorption versus adsorptive bond distance was
      plotted, which is significantly different from that of a harmonic oscillator,
      i.e., the anharmonicity for the adsorptive bond is significant. Also the harmonic
      and anharmonic shifts of vibrational frequencies of adsorptive and C-O bonds are
      calculated to be -22.6 and 7.8 cm(-1), respectively. Hence, two potential models
      are selected for which their Schrodinger equations are solved analytically,
      namely the hard repulsion-soft attraction (HS) and Morse potential (MP) models.
      The adsorption isotherms, internal energy, isochoric heat capacity, and entropy
      of adsorbed CO molecules have been calculated for the mentioned model potentials
      and compared with those of the harmonic oscillator (H). As a result, the
      adsorption isotherms are not considerably sensitive to the model potential. The
      anharmonicity of CO-Ni bond, which is included in HS and MP models, gives an
      average deviation in pressure as much as 1.4% for HS and 5.8% for MP, compared to
      6.1% for the H model. However, isochoric heat capacity and entropy depend on the
      model potential significantly, and the differences may be as high as 69% and 55%
      for isochoric heat capacity and entropy, respectively.

PMID- 17034229
TI  - Diffusion dynamics of the li atom on amorphous carbon: A direct molecular orbital
      molecular dynamics study.
AB  - Direct molecular orbital-molecular dynamics (MO-MD) calculation was applied to
      diffusion processes of the Li atom on a model surface of amorphous carbon and
      compared with the diffusion mechanism of Li+ ion. A carbon sheet composed of
      C96H24 was used as the model surface. The total energy and energy gradient on the
      full dimensional potential energy surface of the LiC96H24 system were calculated
      at each time step in the trajectory calculation. The optimized structure, where
      the Li atom is located at the center of mass of the model surface, was used as
      the initial structure at time zero. Simulation temperatures were chosen in the
      range of 200-1250 K. The dynamics calculations showed that the Li atom vibrates
      around the initial position below 250 K, and it moves above 300 K. At middle
      temperature, the Li atom translates freely on the surface. At higher temperature
      (1000 K), the Li atom moves from the center to edge region of the model surface
      and is trapped in the edge. The activation energy calculated for the Li atom is
      larger than that for the Li+ ion. This difference is due to the fact that the Li
      atom diffuses together with an unpaired electron on the carbon surface. The
      diffusion mechanism of the Li atom was discussed on the basis of the theoretical
      results.

PMID- 17034230
TI  - Understanding the population, coordination, and orientation of water species
      contributing to the nonlinear optical spectroscopy of the vapor-water interface
      through molecular dynamics simulations.
AB  - Molecular dynamics simulations are used to deconvolve the vibrational spectral
      features of the vapor-water interface based on molecular environment. A simple
      geometric description of hydrogen bonding is deployed to identify the OH stretch
      modes that comprise the vibrational sum-frequency spectrum of the vapor-water
      interface with direct comparison to our experimental results. The population
      densities of different species of water molecules are presented as functions of
      interfacial depth and orientation. It is found that surface water molecules that
      possess one proton donor bond and one proton acceptor bond make the dominant
      contribution to both the SSP- and SPS-polarized spectral responses and are
      located within an angstrom of the Gibbs dividing surface.

PMID- 17034231
TI  - Computational studies on polymer adhesion at the surface of gamma-Al2O3. I. The
      adsorption of adhesive component molecules from the gas phase.
AB  - We calculate the minimum energy paths and reaction energies of the adsorption of
      the epoxide adhesive components diglycidylesterbisphenol A (DGEBA),
      diethyltriamine (DETA), and the adhesion promoter 3-aminopropylmethoxysilane
      (AMEO) at two different sites on a model of the native Al2O3 surface, using the
      nudged elastic band algorithm in conjunction with self-consistent charge-density
      functional based tight binding. Our results show that the chosen combination of
      methods is well suited to obtain an overview of the reaction mechanisms and
      kinetics of the adsorption of organic molecules on inorganic surfaces. The
      obtained MEP-s show that there is preference for the adsorption of the adhesion
      promoter, AMEO, over the resin, DGEBA, while the adsorption of the curing agent,
      DETA, is unfavorable. Our approach also gives an insight into the ranges of the
      mechanical and electronic influences of the adsorption process on the interface,
      which neither full ab initio methods nor force field approaches can provide.
      These results will help to develop a quantum mechanics-molecular mechanics
      multiscale embedding scheme for more detailed studies of organic/inorganic hybrid
      interface reactions.

PMID- 17034232
TI  - Hydrated arrays of acidic surface groups as model systems for interfacial
      structure and mechanisms in PEMs.
AB  - We utilize ab initio quantum mechanical calculations in order to explore
      structural conformations and cooperative mechanisms at a minimally hydrated 2D
      array of flexible acidic surface groups. This system serves as a model for
      rationalizing interactions and correlations of protons and water with ionized
      side chains that are affixed to hydrophobic polymer aggregates in polymer
      electrolyte membranes (PEMs). The model exhibits two basic minimum energy
      configurations upon varying the separation of surface groups from 5 to 12 A. In
      the "upright" structure at small separation, surface groups are fully dissociated
      and oriented perpendicular to the basal plane. Together with hydronium ions
      (H3O+) they form a highly ordered network with long-range correlations. At larger
      separations we found the transition to a "tilted" structure with cluster-like
      conformation of surface groups. This structure retains only short-range
      correlations. Moreover, we investigated the strength of water binding to the
      minimally hydrated structures. At small separations between surface groups, an
      additional water molecule interacts only weakly with the minimally hydrated array
      (binding energy < 0.1 eV) while the energy needed to remove one water molecule
      exceeds 1 eV. This shows that the minimally hydrated systems are very stable.
      Ideally, these studies would expedite the design of cheap, highly performing PEMs
      for fuel cells, with a major focus on membranes that could operate stably at
      minimal hydration and elevated temperatures (>120 degrees C).

PMID- 17034233
TI  - Electrochemical impedance spectroscopy investigations of a microelectrode
      behavior in a thin-layer cell: Experimental and theoretical studies.
AB  - Electrochemical impedance spectroscopy experiments were performed on a microdisk
      electrode in a thin-layer cell using a scanning electrochemical microscope for
      controlling the cell geometry. Experimental data showed that when the thin-layer
      thickness diminished, an additional low-frequency response appeared. It was
      ascribed to the radial diffusion of the electroactive species and was strongly
      dependent on the thin-layer dimensions (both thickness and diameter). Moreover,
      the numerical simulation of the impedance diagrams by finite element method
      calculations confirmed this behavior. An equivalent circuit based on a Randles
      type circuit was proposed. Thus, the diffusion was described by introducing two
      electrical elements: one for the spherical diffusion and the other for the radial
      contribution. A nonlinear Simplex algorithm was used, and this circuit was shown
      to fit the impedance diagrams with a good accuracy.

PMID- 17034234
TI  - Heteropolyacid-encapsulated self-assembled materials for anhydrous proton
      conducting electrolytes.
AB  - The composite material of heteropolyacid (12-phosphotungstic acid; PWA) and
      polystyrene sulfonic acid (PSS) construct the PWA-encapsulated material by the
      self-assembly of -SO3H onto the PWA surface; as a result, the fast proton
      transfer occurred at the interface between the PWA and -SO3H, and the
      encapsulated material indicated the high anhydrous proton conductivity of 1 x 10(
      2) S cm(-1) at 180 degrees C. These anhydrous proton-conducting materials without
      the existence of water molecules are quite different from customary ion-exchange
      membrane, such as Nafion, and may have advantages as an electrolyte membrane for
      polymer electrolyte membrane fuel cells operating at intermediate temperatures
      under anhydrous conditions but also for electrochemical devices including
      electrochromic displays, chemical sensors, and others.

PMID- 17034235
TI  - Molecular dynamics simulations of electrolyte solutions at the (100) goethite
      surface.
AB  - Molecular dynamics simulations of electrolyte solutions in contact with a neutral
      (100) goethite (alpha-FeOOH) surface were used to probe the structure of the
      mineral-water interface and gain insight into the adsorption properties of
      monovalent ions. Three electrolyte solutions were considered: NaCl, CsCl, and
      CsF. The electrolyte ions were chosen to cover a range of ionic sizes and
      affinities for the aqueous phase. The molecular dynamics simulations indicate the
      presence of a structured interfacial region resulting from the strong interaction
      of water with the mineral surface. The specific arrangement and preferred
      orientation of water that arise from this interaction create adsorption sites in
      the interfacial region, i.e., as far as 15 A away from the surface, and hence
      give rise to a strong correlation between the water and ion distributions. The
      structure of the hydrated ion, its effect on the water arrangement at the
      interface, and the strength of the ion-water bond are found to be key factors
      that determine the location and extent of ion adsorption at the interface.
      Additionally, in all simulations, we find a build up of positive charges near the
      surface due to cation adsorption, which is compensated by an accumulation of
      anions in the next few angstroms. This creates an excess of negative charges,
      which is in turn compensated by an excess of positive charges, and so on. As we
      modeled a neutral surface, the structure of the electrolyte distribution arises
      from the complex interplay of the interactions between the surface, water, and
      the electrolyte ions rather than from the need to neutralize a surface charge. In
      addition, our simulations indicate that the electrolyte distribution does not
      resemble that of a classical electrical double layer. Indeed, our calculations
      predict the presence of several condensed layers and oscillations in the net
      charge away from the surface.

PMID- 17034236
TI  - Conductivity percolation in loosely compacted microcrystalline cellulose: An in
      situ study by dielectric spectroscopy during densification.
AB  - The present study aims at contributing to a complete understanding of the water
      induced ionic charge transport in cellulose. The behavior of this transport in
      loosely compacted microcrystalline cellulose (MCC) powder was investigated as a
      function of density utilizing a new type of measurement setup, allowing for
      dielectric spectroscopy measurement in situ during compaction. The ionic
      conductivity in MCC was found to increase with increasing density until a
      leveling-out was observed for densities above approximately 0.7 g/cm3. Further,
      it was shown that the ionic conductivity vs density followed a percolation type
      behavior signifying the percolation of conductive paths in a 3D conducting
      network. The density percolation threshold was found to be between approximately
      0.2 and 0.4 g/cm3, depending strongly on the cellulose moisture content. The
      observed percolation behavior was attributed to the forming of interparticulate
      bonds in the MCC and the percolation threshold dependence on moisture was linked
      to the moisture dependence of particle rearrangement and plastic deformation in
      MCC during compaction. The obtained results add to the understanding of the
      density-dependent water-induced ionic transport in cellulose showing that, at
      given moisture content, the two major parameters determining the magnitude of the
      conductivity are the connectedness of the interparticluate bonds and the
      connectedness of pores with a diameter in the 5-20 nm size range. At densities
      between approximately 0.7 and 1.2 g/cm3 both the bond and the pore networks have
      percolated, facilitating charge transport through the MCC compact.

PMID- 17034237
TI  - Structural study of NO adsorbed on the reconstructed Pt(110)-(1 x 2) surface with
      X-ray photoelectron diffraction and near-edge X-ray absorption fine structure
      spectroscopy.
AB  - The adsorption structure of NO on the reconstructed Pt(110)-(1 x 2) surface was
      studied with X-ray photoelectron spectroscopy (XPS), X-ray photoelectron
      diffraction (XPD), low-energy scanned-angle photoelectron diffraction (LESA-PD),
      and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The
      experiments were performed at 180 K, where no surface lifting from (1 x 2) to (1
      x 1) takes place after NO adsorption. XPS indicates that the (1 x 2) unit cell of
      the Pt(110) surface contains 1.5 NO molecules at the saturated coverage. XPD and
      LESA-PD analyses allow us to propose a structural model for the NO adlayer, where
      two-thirds of the NO molecules in the (1 x 2) unit cell are adsorbed on the atop
      site of the close-packed Pt rows (ridges) along the [10] direction with an
      inclined geometry and one-third of the NO molecules adsorb on the bridge site
      between the Pt ridges with an upright configuration. This model is supported by
      the N K-edge NEXAFS experiments and is consistent with the recently reported
      model based on the density functional theory (Orita, H.; Nakamura, I.; Fujitani,
      T. J. Phys. Chem. B 2005, 109, 10312).

PMID- 17034238
TI  - Spacer and anchor effects on the electronic coupling in ruthenium-bis-terpyridine
      dye-sensitized TiO2 nanocrystals studied by DFT.
AB  - Structural and electronic properties of TiO2 nanoparticles sensitized with a set
      of Ru(II)(tpy)2 based dyes have been investigated using density functional theory
      (DFT) calculations combined with time-dependent (TD) DFT calculations. The
      effects of carboxylic and phosphonic acid anchor groups, as well as a phenylene
      spacer group, on the optical properties of the dyes and the electronic
      interactions in the dye-sensitized TiO2 nanoparticles have been investigated.
      Inclusion of explicit counterions in the modeling shows that the description of
      the environment is important in order to obtain a realistic interfacial energy
      level alignment. A comparison of calculated electronic coupling strengths
      suggests that both the nature of the anchor group and the inclusion of the
      phenylene spacer group are capable of significantly influencing electron-transfer
      rates across the dye-metal oxide interface.

PMID- 17034239
TI  - Enhancement of topographic images obtained in liquid media by atomic force
      microscopy.
AB  - The open liquid-cell atomic force microscope (AFM) has potential for studies of
      biomaterials and surface morphology in liquid media, and a variety of fluids can
      be used as buffer solutions. The dependence of image distortion on fluid
      properties (kinematic viscosity) has been studied with edge friction force
      obtained in lateral images and will shortly appear elsewhere [Appl. Phys. Lett.
      2006, 88, 173121]. Previous studies indicate that the scan rate should be slower
      for obtaining a nondistorted image. However, the time required for the scan is
      greatly increased. Therefore, we introduced the vector concept to evaluate the
      net force for scanning in the y-direction and found two solutions to achieve a
      zero force difference introduced by the cantilever-fluid and the tip-surface.
      When the scan rate approaches zero or a specific velocity (30 microm/s in this
      study), the force of the interaction induced by the cantilever-fluid and tip
      surface is reduced to a considerable extent. Among the two solutions, a scan with
      a specific velocity is an easy, rapid method for obtaining a nondistorted image,
      compared to the previously proposed method (scan rate approaches zero). This
      proposed model was confirmed in a proof-of-concept test using 2-propanol.

PMID- 17034240
TI  - Structuring effects and hydration phenomena in poly(ethylene glycol)/water
      mixtures investigated by brillouin scattering.
AB  - Aqueous solutions of poly(ethylene glycol) (PEG) of mean molecular mass of 600
      g/mol (PEG600) are investigated by Brillouin scattering technique. At high PEG
      content, a relaxation phenomenon is observed, which is related to a local
      rearrangement of the polymer structure where the interaction, via hydrogen
      bonding, with the solvent molecules plays a role. The obtained values of the
      relaxation times match the literature data very well for a fast relaxation time
      revealed by dielectric relaxation measurements in very similar mixtures. The
      calculated concentration behaviors of the excess adiabatic compressibility turns
      out in good agreement with the previous findings from ultrasonic measurements at
      3 MHz. The observed minimum in the adiabatic compressibility is interpreted as
      the result of the interaction between water and the EO units of the PEG chain,
      which results in a structure tighter then that typical of bulk water and of pure
      PEG600. Such a hypothesis is supported by the observation that volume fraction
      value of about 0.3 coincides with the concentration value at which full hydration
      of EO units takes place. The observation that at the same concentration, the
      polymer coils start to overlap each other further supports the idea that the
      adiabatic compressibility behavior is monitoring the structural evolution of the
      mixture. However, similar results are obtained for largely different binary
      mixture which suggests caution in taking this conclusion too literally. In
      particular, the hypothesis that the occurrence of an extreme in the excess
      adiabatic compressibility could be simply originated by statistical effects and
      that further work is required for disentangling entropic contribution from
      effects of hetero-association and self-aggregation of one or both the components.

PMID- 17034241
TI  - Critical endpoint and analytical phase diagram of attractive hard-core Yukawa
      spheres.
AB  - We analytically calculate the gas-liquid critical endpoint (cep) for hard spheres
      with a Yukawa attraction. This cep is a boundary condition for the existence of a
      liquid. We use an analytical Helmholtz energy expression for the attractive
      Yukawa (hard) spheres based on the first-order mean spherical approximation to
      the attractive Yukawa potential by Tang and Lu (J. Chem. Phys. 1993, 99, 9828).
      This theory and our analytical simplification of it predict the gas-liquid and
      fluid-solid phase behavior, as found from computer simulations, very accurately
      as long as the range 1/kappa of attraction is not too short. We find that the cep
      is situated at kappasigma approximately 6 and at a contact potential around 2 kT.
      It follows that a liquid state is only possible when the attraction range is
      longer than (1/6) of the particle diameter sigma, and the attraction strength is
      smaller than 2 kT. The liquid region does not span more than 0.6 kT in strength,
      and there is also a relatively narrow window for the attraction range.

PMID- 17034242
TI  - Computational determination of aqueous pKa values of protonated benzimidazoles
      (Part 2).
AB  - Our aim is to develop an effective computational procedure for predicting the
      aqueous acid equilibrium constants of protonated benzimidazoles at 298.15 K. The
      experimental determination of these values, apart from been laborious, is a
      challenge because of the low water solubility of these compounds. Using a variety
      of descriptors, quantitative structure-property relationships (QSPR) are explored
      between the experimental aqueous pKa values of a group of fifteen benzimidazoles
      and descriptors calculated at the B3LYP/6-31+G(d,p) level of theory. Solvent
      effects are taken into account with the PCM solvation model through both single
      point energy calculations (PCM(sp)), and in the geometry optimizations and
      frequency calculations (PCM(opt)). Descriptors considered are the Gibbs free
      energy change of the acid equilibrium in water, the charges on the acidic
      hydrogen, and on the basic nitrogen, several orbital energies of the protonated
      and neutral species, and the volume of the solvent cavity. Multiple linear
      regressions are used to correlate descriptors to the experimental pKa values.
      Several QSPR equations reproduce the experimental data more accurately, and show
      stronger correlations than previously attempted methodologies. The predictive
      capabilities of the QSPR methodologies are tested with four compounds that were
      not included in the set of benzimidazoles initially investigated. In addition, a
      correlation between experimental pKa values in water and in a 50% ethanol-water
      solution is used to estimate aqueous pKa values.

PMID- 17034243
TI  - Modeling of folding and unfolding mechanisms in alanine-based alpha-helical
      polypeptides.
AB  - alpha-Helix formation is known to be opposed by the entropy loss due to the
      folding and favored by the energy of molecular interactions. However, the
      underlying mechanism of these factors is still being discussed. Here we have used
      the experimental and calculation data for short alanine-based peptides embedded
      in water to model the mechanism of helix folding and unfolding and to calculate
      microscopically the free energy factors of alanine in the frame of helix coil
      conformational integrals. Classical helix-coil transition theories take into
      account the interactions in a peptide chain only if the i, i + 3 peptide bond
      participates in hydrogen bonding. But quantum mechanical calculations showed that
      interactions of the i, i + 2 peptide bond play an important role in helix folding
      too. We also included the short-range repulsive interactions due to molecular
      steric clashes and the end effects due to polar/hydrogen-bonding interactions at
      the N and C termini. The helix and coil regions of peptide conformational space
      were defined using an experimental steric criterion for hydrogen bonding.
      Arginine helix propensity was discussed and estimated. Monte Carlo numerical
      simulations of thermodynamics and kinetics for the 21 amino acid alpha-helical
      polypeptide Ac-A5(AAARA)3A-NMe were carried out and found to be in an agreement
      with the experimental results.

PMID- 17034244
TI  - Aggregation of antifreeze protein and impact on antifreeze activity.
AB  - Antifreeze protein type III aggregates once the concentration exceeds a critical
      value, the so-called critical aggregation concentration (CAC). It was found for
      the first time that the aggregation of antifreeze protein exerts a direct impact
      on the antifreeze efficiency. It follows from our measurements that the AFP III
      above CAC will enhance the antifreeze activity because of the increase of the
      kink kinetics barrier of surface integration. This is attributed to the optimal
      packing of AFP III molecules on the surface of the ice nucleus as well as ice
      crystals above CAC. This study will extend our understanding of the antifreeze
      mechanism of antifreeze protein monomers as well as antifreeze aggregates on ice
      nucleation and shed light on the selection of antifreeze agents.

PMID- 17034245
TI  - Multiple DNA binding modes of a metallointercalator revealed by DNA film
      voltammetry.
AB  - Binding and the redox reaction of the metallointercalator Ru(bpy)2(dppz)2+ (bpy =
      2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine) with DNA was
      investigated by DNA film voltammetry. Calf-thymus DNA (CT-DNA) was assembled on a
      tin-doped indium oxide electrode by layer-by-layer electrostatic adsorption.
      Voltammetry of Ru(bpy)2(dppz)2+ (Ru-dppz) bound to the DNA film was measured in a
      redox-free electrolyte and showed strong dependence on the concentration of the
      metallointercalator. At low Ru-dppz concentrations, a single oxidation peak was
      observed, the potential of which shifted from 1.25 to 1.1 V with increasing Ru
      dppz concentration (peak 1). At high metal chelate concentrations, an additional
      oxidation peak emerged with a potential of 1.25 V which was unaffected by the Ru
      dppz concentration (peak 2). Three experiments were performed to investigate the
      mechanism and structural basis of the multiple peaks. First, voltammetry of
      Os(bpy)2(dppz)2+ bound to the CT-DNA film displayed only one peak at its
      oxidation potential of about 0.75 V. Second, the concentration dependence of Ru
      dppz bound to a poly-(AU) film (which does not contain any guanine bases)
      exhibited only one oxidation peak at about 1.22 V that was independent of the Ru
      dppz concentration. Third, when the guanine concentration in a mixed film of CT
      DNA and poly-(AU) was changed and the bound Ru-dppz was kept constant, a pre-peak
      emerged and shifted to 1.1 V with increasing guanines. Based on these results,
      the appearance of two peaks in the voltammetric measurements of CT-DNA was
      rationalized by invoking two different DNA binding modes for the Ru-dppz complex:
      intercalation and electrostatic association. Peak 2 arises from slow oxidation of
      guanines catalyzed by Ru-dppz electrostatically associated with the DNA film,
      since the addition of Mg2+ decreases the magnitude of peak 2. Peak 1 was not
      affected by Mg2+ ions, leading us to conclude that it is due to intercalated Ru
      dppz. The intercalation positions the metal complex in close contact with the
      guanines inside DNA resulting in fast electrocatalytic reaction, giving rise to a
      catalytic pre-peak.

PMID- 17034247
TI  - 15N MAS NMR studies of cph1 phytochrome: Chromophore dynamics and intramolecular
      signal transduction.
AB  - Solid-state nuclear magnetic resonance (NMR) is applied for the first time to the
      photoreceptor phytochrome. The two stable states, Pr and Pfr, of the 59-kDa N
      terminal module of the cyanobacterial phytochrome Cph1 from Synechocystis sp. PCC
      6803 containing a uniformly 15N-labeled phycocyanobilin cofactor are explored by
      15N cross-polarization (CP) magic-angle spinning (MAS) NMR. As recently shown by
      15N solution-state NMR using chemical shifts [Strauss, H. M.; Hughes, J.;
      Schmieder, P. Biochemistry 2005, 44, 8244], all four nitrogens are protonated in
      both states. CP/MAS NMR provides two additional independent lines of evidence for
      the protonation of the nitrogens. Apparent loss of mobility during
      photoactivation, indicated by the decrease of line width, demonstrates strong
      tension of the entire chromophore in the Pfr state, which is in clear contrast to
      a more relaxed Pr state. The outer rings (A and D) of the chromophore are
      significantly affected by the phototransformation, as indicated by both change of
      chemical shift and line width. On the other hand, on the inner rings (B and C)
      only minor changes of chemical shifts are detected, providing evidence for a
      conserved environment during phototransformation. In a mechanical model, the
      phototransformation is understood in terms of rotations between the A-B and C-D
      methine bridges, allowing for intramolecular signal transduction to the protein
      surface by a unit composed of the central rings B and C and its tightly linked
      protein surroundings during the highly energetic Pfr state.

PMID- 17034246
TI  - Quantification of surface-bound proteins by fluorometric assay: Comparison with
      quartz crystal microbalance and amido black assay.
AB  - Protein adsorption is of major and widespread interest, being useful in the
      fundamental understanding of biological processes at interfaces through to the
      development of new materials. A number of techniques are commonly used to study
      protein adhesion, but few are directly quantitative. Here we describe the use of
      Nano Orange, a fluorometric assay, to quantitatively assess the adsorption of
      bovine fibrinogen and albumin onto model hydrophilic (OH terminated) and
      hydrophobic (CH3 terminated) surfaces. Results obtained using this method allowed
      the calibration of previously unquantifiable data obtained on the same surfaces
      using quartz crystal microbalance measurements and an amido black protein assay.
      Both proteins were found to adsorb with higher affinity but with lower saturation
      levels onto hydrophobic surfaces. All three analytical techniques showed similar
      trends in binding strength and relative amounts adsorbed over a range of protein
      concentrations, although the fluorometric analysis was the only method to give
      absolute quantities of surface-bound protein. The versatility of the fluorometric
      assay was also probed by analyzing protein adsorption onto porous
      superhydrophobic and superhydrophilic surfaces. Results obtained using the assay
      in conjunction with these surfaces were surface chemistry dependent. Imbibition
      of water into the superhydrophilic coatings provided greater surface area for
      protein adsorption, although the protein surface density was less than that found
      on a comparable flat hydrophilic surface. Superhydrophobic surfaces prevented
      protein solution penetration. This paper demonstrates the potential of a
      fluorometric assay to be used as an external calibration for other techniques
      following protein adsorption processes or as a supplemental method to study
      protein adsorption. Differences in protein adsorption onto hydrophilic vs
      superhydrophilic and hydrophobic vs superhydrophobic surfaces are highlighted.

PMID- 17034248
TI  - Intermolecular vibrational coherence in bacteriochlorophyll a with clustered
      polar solvent molecules.
AB  - We show that resonant impulsive excitation of the Qy absorption band of
      bacteriochlorophyll a (BChl) launches a rapidly damped (gamma < 200 fs) ground
      state coherent wave-packet motion that arises from intermolecular modes with
      clustered solvent molecules. Femtosecond pump-probe, dynamic-absorption signals
      were obtained at room temperature with BChl solutions in pyridine, acetone, and 1
      propanol. The vibrational coherence observed in the 0-800-fs regime is modeled in
      the time domain by two (or three, in the case of 1-propanol) modulation
      components with asymmetric, inhomogeneously broadened line shapes and frequencies
      in the 100-200-cm(-1) range. The mean frequency of the vibrational coherence
      exhibits at least a quadratic dependence on the dipole moment of the solvent
      molecules and a y-intercept in the 100-cm(-1) regime. This trend is modeled by an
      expression for the natural frequency of a "6-12" potential composed of attractive
      terms from van der Waals forces and a repulsive term from the exchange (Pauli
      exclusion) force. The model suggests that comparable contributions to the
      potential are provided by the dipole-dipole and London dispersion interactions.
      These results support the hypothesis that the low-frequency vibrational modes in
      the 100-cm(-1) regime that are coupled to the light-driven charge-separation
      reactions in the reaction center from purple bacteria are derived from
      intermolecular vibrational modes between the chromophores and the surrounding
      protein medium.

PMID- 17034249
TI  - Assessing induced folding of an intrinsically disordered protein by site-directed
      spin-labeling electron paramagnetic resonance spectroscopy.
AB  - We used site-directed spin-labeling electron paramagnetic resonance (EPR)
      spectroscopy to study the induced folding of the intrinsically disordered C
      terminal domain of measles virus nucleoprotein (N(TAIL)). Four single-site
      N(TAIL) mutants (S407C, S488C, L496C, and V517C), located in three conserved
      regions, were prepared and labeled with a nitroxide paramagnetic probe. We could
      monitor the gain of rigidity that N(TAIL) undergoes in the presence of either the
      secondary structure stabilizer 2,2,2-trifluoroethanol (TFE) or one of its
      physiological partners, namely, the C-terminal domain (XD) of the viral
      phosphoprotein. The mobility of the spin label grafted at positions 488, 496, and
      517 was significantly reduced upon addition of XD, contrary to that of the spin
      label bound to position 407, which was unaffected. Furthermore, the EPR spectra
      of spin-labeled S488C and L496C bound to XD in the presence of 30% sucrose are
      indicative of the formation of an alpha-helix in the proximity of the spin
      labels. Such an alpha-helix had been already identified by previous biochemical
      and structural studies. Using TFE we unveiled a previously undetected structural
      propensity within the N-terminal region of N(TAIL) and showed that its C-terminal
      region "resists" gaining structure even at high TFE concentrations. Finally, we
      for the first time showed the reversibility of the induced folding process that
      N(TAIL) undergoes in the presence of XD. These results highlight the suitability
      of site-directed spin-labeling EPR spectroscopy to identify protein regions
      involved in binding and folding events, while providing insights at the residue
      level.

PMID- 17034250
TI  - Dielectric studies of water clusters in cyclodextrins: Relevance to the
      transition between slow and fast forms of thrombin.
AB  - Cyclodextrins are useful models in the study of hydrogen bonded water clusters.
      In alpha-cyclodextrin hexahydrate (alpha-CD.6H2O), water molecules are ordered
      and occupy well-defined positions whereas in the larger beta-cyclodextrin
      dodecahydrate (beta-CD.12H2O), there is considerable disorder with water
      molecules freely arranged over several possible sites. Here it is shown that beta
      CD exhibits substantial structural flexibility and proton mobility compared with
      alpha-CD which is relatively very rigid and exhibits negligible short-range
      protonic conduction. These properties are directly controlled by the effective
      dielectric constant of the molecule, which is determined by the rotational
      freedom of water molecules in the hydrogen bond network. This model may be
      relevant to proteins where water clusters of this kind are found on the protein
      surface and occasionally in the protein interior. The case of thrombin, an
      allosteric enzyme incorporating a network of 20 internal hydrogen bonded water
      molecules, is discussed.

PMID- 17034251
TI  - Methyl dynamics in proteins from NMR slowly relaxing local structure spin
      relaxation analysis: A new perspective.
AB  - NMR spin relaxation of (2)H nuclei in (13)CH(2)D groups is a powerful method for
      studying side-chain motion in proteins. The analysis is typically carried out
      with the original model-free (MF) approach adapted to methyl dynamics. The latter
      is described in terms of axial local motions around, and of, the methyl averaging
      axis, mutually decoupled and independent of the global motion of the protein.
      Methyl motion is characterized primarily by the axial squared order parameter,
      S(axis)2, associated with fluctuations of the methyl averaging axis. This view is
      shown to be oversimplified by applying to typical experimental data the slowly
      relaxing local structure (SRLS) approach of Polimeno and Freed (Adv. Chem. Phys.
      1993, 83, 89) which can be considered the generalization of the MF approach.
      Neglecting mode coupling and the asymmetry of the local ordering and treating
      approximately features of local geometry imply inaccurate values of S(axis)2,
      hence of the residual configurational entropy derived from it. S(axis)2,
      interpreted as amplitude of motion, was found to range from near disorder to
      almost complete order. Contrary to this picture, we find with the SRLS approach a
      moderate distribution in the magnitude of asymmetric local ordering and
      significant variation in its symmetry. The latter important property can be
      associated implicitly with the contribution of side-chain rotamer jumps. This is
      consistent with experimental residual dipolar coupling studies and theoretical
      work based on molecular dynamics simulations and molecular mechanics
      considerations. Configurational entropy is obtained in the SRLS approach directly
      from experimentally determined asymmetric potentials. Inconsistency between order
      parameters from 2H relaxation and from eta(HC-HH) cross-correlation and increase
      in order parameters with increasing temperature were observed with the MF
      approach. These discrepancies are reconciled, and physically tenable temperature
      dependence is obtained with the SRLS approach.

PMID- 17034252
TI  - Exploration of the secondary structure specific differential solvation dynamics
      between the native and molten globule states of the protein HP-36.
AB  - Recent experiments have shown that the time dependence of fluorescence Stokes
      shift of a chromophore is substantially different when the chromophore is located
      in a molten globule (MG) state and in the native state of the same protein. To
      understand the origin of this difference, particularly the role of water in the
      differential solvation of the protein in the native and the MG states, we have
      carried out fully atomistic molecular dynamics simulations with explicit water of
      a partially unfolded MG state of the protein HP-36 and compared the results with
      the solvation dynamics of the protein in the folded native state. It is observed
      that the polar solvation dynamics of the three helical segments of the protein is
      influenced in a nonuniform heterogeneous manner in the MG state. While the
      equilibrium solvation time correlation function for helix-3 has been found to
      relax faster in the MG state as compared to that in the native state, the decay
      of the corresponding function for the other two helices slows down in the MG
      state. A careful analysis shows that the origin of such heterogeneous relative
      solvation behavior lies in the differential location of the polar probe residues
      and their exposure to bulk solvent. We find a significant negative cross
      correlation between the contribution (to the solvation energy of a tagged amino
      acid residue) of water and the other groups of the protein, indicating a
      competing role in solvation. The sensitivity of solvation dynamics to the
      secondary structure and the immediate environment can be used to discriminate the
      partially unfolded and folded states. These results therefore should be useful in
      explaining recent solvation dynamics experiments on native and MG states of
      proteins.

PMID- 17034253
TI  - Temperature-controlled release of diols from N-isopropylacrylamide-co
      acrylamidophenylboronic acid microgels.
AB  - N-Isopropylacrylamide-co-acrylamidophenylboronic acid (NIPAM-co-PBA) microgels
      were prepared by free radical polymerization in water. The release of glucose and
      Alizarin Red S (ARS) from the microgels as a function of temperature has been
      investigated by using laser light scattering (LLS) and ultrasensitive
      differential scanning calorimetry (US-DSC). Such microgels can bind glucose and
      ARS via boronic acids at a lower temperature. As the temperature increases, the
      microgels shrink, and the diols are released. The release could be controlled by
      temperature. The effect of the structure of the microgels on the release is also
      discussed.

PMID- 17034254
TI  - Blocking of the nicotinic acetylcholine receptor ion channel by chlorpromazine, a
      noncompetitive inhibitor: A molecular dynamics simulation study.
AB  - A large series of pharmacological agents, distinct from the typical competitive
      antagonists, block in a noncompetitive manner the permeability response of the
      nicotinic acetylcholine receptor (nAChR) to the neurotransmitter acetylcholine.
      Taking the neuroleptic chlorpromazine (CPZ) as an example of such agents, the
      blocking mechanism of noncompetitive inhibitors to the ion channel pore of the
      nAChR has been explored at the atomic level using both conventional and steered
      molecular dynamics (MD) simulations. Repeated steered MD simulations have
      permitted calculation of the free energy (approximately 36 kJ/mol) of CPZ binding
      and identification of the optimal site in the region of the serine and leucine
      rings, at approximately 4 A from the pore entrance. Coulomb and the Lennard-Jones
      interactions between CPZ and the ion channel as well as the conformational
      fluctuations of CPZ were examined to assess the contribution of each to the
      binding of CPZ to the nAChR. The MD simulations disclose a dynamic interaction of
      CPZ binding to the nAChR ionic channel. The cationic ammonium head of CPZ forms
      strong hydrogen bonds with Glu262 (alpha), Asp268 (beta), Glu272 (beta), Ser276
      (beta), Glu280 (delta), Gln271 (gamma), Glu275 (gamma), and Asn279 (gamma) nAChR
      residues. Finally, the conventional MD simulation of CPZ at its identified
      binding site demonstrates that the binding of CPZ not only blocks ion transport
      through the channel but also markedly inhibits the conformational transitions of
      the channel, necessary for nAChR to carry out its biological function.

PMID- 17034255
TI  - Monitoring interfacial bioelectrochemistry using a FRET switch.
AB  - Generation of functionally active biomolecular monolayers is important in both
      analytical science and biophysical analyses. Our ability to monitor the redox
      active state of immobilized proteins or enzymes at a molecular level, from which
      stochastic and surface-induced variations would be apparent, is impeded by
      comparatively slow electron-transfer kinetics and associated signal:noise
      difficulties. We demonstrate herein that by covalently tethering an appropriate
      dye to the copper protein azurin a highly oxidation-state-sensitive FRET process
      can be established which enables redox switching to be optically monitored at
      protein levels down to the zeptomolar limit. The surface-potential-induced
      cycling of emission enables the redox potential of clusters of a few hundred
      molecules to be determined.

PMID- 17034256
TI  - Complexation of copper(II)-Chelidamate: A multifrequency-pulsed electron
      paramagnetic resonance and electron nuclear double resonance analysis.
AB  - Multifrequency electron paramagnetic resonance (EPR) and electron nuclear double
      resonance (ENDOR) techniques were used to obtain structural information about the
      copper(II)-chelidamate complex. Well-resolved nitrogen ENDOR spectra could be
      recorded from solid solution samples by using selective excitation of spin
      packets. Evaluation of nuclear quadrupole and dipolar hyperfine interaction of
      the directly ligated nitrogen allowed for an identification of the bond direction
      to the copper ion within the eigen frame of the copper g-matrix. Invoking two
      dimensional EPR techniques, additional hyperfine interaction with a "distant"
      nitrogen spin, identified as resulting from the solvent dimethylformamide (DMF),
      was observed. The experimental data are only consistent with formation of a
      stable pseudoplanar copper complex with single solvent ligation via its oxygen
      atom.

PMID- 17034257
TI  - Analysis and parametric optimization of 1H off-resonance relaxation NMR
      experiments designed to map polypeptide self-recognition and other noncovalent
      interactions.
AB  - The measurement of 1H off-resonance nonselective relaxation rates (R(theta,ns))
      has been recently proposed as an effective method to probe peptide self
      recognition, opening new perspectives in the understanding of the
      prefibrillization oligomerization processes in amylodogenesis. However, a full
      analysis and parametric optimization of the NMR experiments designed to measure
      R(theta,ns) relaxation rates is still missing. Here we analyze the dependence of
      the R(theta,ns) rates upon three critical parameters: the tilt angle of the
      effective field during the spin lock, the static magnetic field, and finally the
      repetition delay. Our analysis reveals that the tilt angle theta = 35.5 degrees
      not only minimizes spin-diffusion, but also avoids experimental artifacts such as
      J-transfer and poor adiabaticity. In addition, we found that when the dominant
      relaxation mechanism is caused by uncorrelated pairwise 1H dipole-1H dipole
      interactions the R(35.5 degrees,ns) rate is not significantly affected by static
      field variations, suggesting a wide applicability of the 1H off-resonance
      nonselective relaxation experiment. Finally, we show that the self-recognition
      maps based on the comparative analysis of the R(35.5 degrees,ns) rates can
      tolerate decreases in the interscan delays without significantly compromising the
      identification of critical self-association loci. These considerations not only
      provide a better understanding of the 1H off-resonance nonselective relaxation,
      but they also serve as guidelines for the optimal setup of this experiment.

PMID- 17034258
TI  - Mechanism of ion permeation in a model channel: Free energy surface and dynamics
      of K+ ion transport in an anion-doped carbon nanotube.
AB  - The mechanism of the ion permeation is investigated for an anion-doped carbon
      nanotube, as a model of the K+ channel, by analyzing the free energy surface and
      the dynamics of the ion permeation through the model channel. It is found that
      the main rate-determining step is how an ion enters the channel. The entrance of
      the ion is mostly blocked by a water molecule located at this entrance. Only
      about 10% of K+ ions which reach the mouth of the channel can really enter the
      channel. The rejection rate sensitively depends on the location of this water
      molecule, which is easily controlled by the charge of the carbon nanotube; for
      example, the maximum permeation is obtained when the anion charge is at a certain
      value, -5.4e in the present model. At this charge, the facile translocation of
      the ion inside the channel is also induced due to the number of fluctuations of
      the ions inside the channel. Therefore, the so-called "Newton's balls", a toy
      model, combined with a simple ion diffusion model for explaining the fast ion
      permeation should be modified. The present analysis thus suggests that there
      exists an optimum combination of the length and the charge of the carbon nanotube
      for the most efficient ion permeation.

PMID- 17034260
TI  - Comparative computational analysis of different active site conformations and
      substrates in a chalcone isomerase catalyzed reaction.
AB  - Chalcone isomerase catalyzes the transformation of chalcones to flavanones. We
      present a computational study of the rate-limiting chemical step, an
      intramolecular Michael addition of a 2'-oxyanion to the alpha,beta-double bound.
      By using quantum mechanical/molecular mechanical hybrid methods we traced the
      free-energy profiles associated with the reaction of two different substrates
      (chalcone and 6'-deoxychalcone) in two different conformations of the active site
      that are described in the different crystallographic structures available. We
      have obtained significant differences (about 4 kcal/mol) in the free-energy
      barriers calculated for the two active sites. According to our results, the
      active site conformation with larger catalytic power presents a positively
      charged lysine residue much closer to the substrate than the other. Complementary
      electronic and electrostatic analysis shows that the charge is transferred from
      the 2'-oxyanion to the beta-carbon atom. Interactions of the environment with
      these two atoms are essential to understand the differences between both active
      sites and also the origin of catalysis in this enzyme.

PMID- 17034259
TI  - Role of aspartic acid in collagen structure and stability: A molecular dynamics
      investigation.
AB  - A molecular dynamics (MD) simulation study has been carried out to understand the
      stability of the triple helical collagen models. The calculations show that the
      presence of the aspartic acid residue in different positions leads to the local
      variation in the structure. Analyses of root-mean-square deviation (RMSD), radial
      distribution function (RDF), puckering effect, dihedral angle variation, hydrogen
      bond (H-bond), and conformational changes during molecular dynamics simulation
      reveal that the local perturbation in the sequences, increase in chain
      flexibility due to removal of five membered rings in the collagen by aspartic
      acid, change of intermolecular H-bonding pattern, and differences in the
      association of water are mainly influencing the nature of stabilization of
      collagen by aspartic acid.

PMID- 17034261
TI  - Contributions of hydroxyethyl groups to the DNA binding affinities of anthracene
      probes.
AB  - Contributions of hydroxyethyl functions to the DNA binding affinities of
      substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal
      titration calorimetry indicated that binding of the ligands to calf thymus DNA (5
      mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding
      constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of
      increase in the number of hydroxyethyl functions (0-4). DNA binding was
      accompanied by red-shifted absorption (approximately 630 cm(-1)), strong
      hypochromism (>65%), positive induced-circular dichroism bands, and negative
      linear dichroism signals. DNA binding, in general, increased the helix
      stabilities to a significant extent (DeltaT(m) approximately 7 degrees C,
      DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol).
      The binding constants showed a strong correlation with the number of hydroxyethyl
      groups present on the anthracene ring system. Analysis of the binding data using
      the hydrophobicity parameter (Log P) showed a poor correlation between the
      binding affinity and hydrophobicity. This observation was also supported by a
      comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1))
      versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very
      first examples of a strong quantitative correlation between the DNA binding
      affinity of a probe and the number of hydroxyethyl groups present on the probe.
      These quantitative findings are useful in the rational design of new ligands for
      high-affinity binding to DNA.

PMID- 17034263
TI  - Enhancement of lithium amide to lithium imide transition via mechanical
      activation.
AB  - The decomposition of lithium amide (LiNH2) to lithium imide (Li2NH) and ammonia
      (NH3) with and without high-energy ball milling is investigated to lay a
      foundation for identifying methods to enhance the hydrogen uptake/release of the
      lithium amide and lithium hydride mixture. A wide range of analytical instruments
      are utilized to provide unambiguous evidence of the effect of mechanical
      activation. It is shown that ball milling reduces the onset temperature for the
      decomposition of LiNH2 from 120 degrees C to room temperature. The enhanced
      decomposition via ball milling is attributed to mechanical activation related to
      the formation of nanocrystallites, the reduced particle size, the increased
      surface area, and the decreased activation energy. The more mechanical activation
      there is, then the more improvement there is in enhancing the decomposition of
      LiNH2. It also is found that the activation energy for the decomposition of LiNH2
      without ball milling is 243.98 kJ/mol, which is reduced to 222.20 kJ/mol after
      ball milling at room temperature for 45 min and is further reduced to 138.05
      kJ/mol after ball milling for 180 min. The rate of the isothermal decomposition
      at the later phase of the LiNH2 decomposition is controlled by diffusion of NH3
      through the Li2NH layer.

PMID- 17034262
TI  - Cryogenic photolysis of activated bleomycin to ferric bleomycin.
AB  - Activated bleomycin (ABLM) is a drug--Fe(III)-hydroperoxide complex kinetically
      competent in DNA attack (via H4' abstraction). This intermediate is relatively
      stable, but its spontaneous conversion to ferric bleomycin (Fe(III).BLM) is
      poorly characterized because no observable intermediate product accumulates.
      Light was shown to trigger ABLM attack on DNA in liquid at -30 degrees C, so ABLM
      was irradiated (at its 350 nm ligand-to-metal charge-transfer transition) at 77 K
      to stabilize possible intermediates. ABLM photolysis (quantum yield, Phi = 0.005)
      generates two kinds of product: Fe(III).BLM (with no detectable intermediate) and
      one or more minor (1-2%) radical O-Fe-BLM byproduct, photostable at 77 K. Adding
      DNA, even without its target H4', increases the quantum yield of ABLM conversion
      >10-fold while suppressing the observed radical yield. Since cryogenic solid
      phase reactions can entail only constrained local rearrangement, the reaction(s)
      converting ABLM to Fe(III).BLM must be similarly constrained.

PMID- 17034264
TI  - Comment on "Examination of spinel and nonspinel structural models for gamma-Al2O3
      by DFT and Rietveld refinement simulations".

PMID- 17034265
TI  - Comment on "Examination of spinel and nonspinel structural models for gamma-Al2O3
      by DFT and Rietveld refinement simulations".

PMID- 17034267
TI  - Driving: the ultimate IADL.

PMID- 17034268
TI  - Driver safety in older adults. The physician's role in assessing driving skills
      of older patients.
AB  - Physicians play an important role in addressing driving safety issues with their
      patients. This is especially true when age-associated changes, medical conditions
      and medications are likely to increase crash risk. Unfortunately, physicians have
      little or no training in determining crash risk. Furthermore they are reluctant
      to alienate their patients by raising concerns about driving. In response to a
      growing need, the American Medical Association (AMA), with support from the
      National Highway Traffic Safety Administration (NHTSA), has produced materials to
      help physicians approach this issue. This article provides background about the
      aging and medical influences on driving, a summary of selected information from
      the AMA guide, and additional resources.

PMID- 17034269
TI  - Patient reports six-month history of minimally pruritic purple dots on legs. Non
      blanching macules developed over six months.

PMID- 17034270
TI  - Alcohol use in the elderly: beyond the CAGE. Part 1 of 2: prevalence and patterns
      of problem drinking.
AB  - It has been estimated that 33% of adults age 65 and older have consumed alcohol
      during the preceding month; 25% of these drinkers (31% of men, 19% of women)
      drink daily and approximately 10% drink five drinks on one occasion. Alcohol
      misuse, with or without dependence, increases an older patient's risks of
      physical and mental problems. Yet hazardous drinking often is not identified in
      the elderly because ageism, denial, coexisting disabilities, and the unique
      pattern of late-onset drinking frequently mask its presence and complicate the
      diagnosis.

PMID- 17034271
TI  - Chemiluminescence associated with singlet oxygen reactions with amino acids,
      peptides and proteins.
AB  - Low level chemiluminescence (CL) is observed after protein oxidation mediated by
      singlet oxygen produced in Rose Bengal (RB) irradiation. This CL lasts for
      several minutes after the end of the photolysis. In this work, the mechanism of
      the process was assessed from the spectral characteristics of the CL and the
      effect of antioxidants (Trolox or ascorbate), Ebselen (a compound with peroxidase
      like activity), azide (a singlet oxygen scavenger) and D2O, added prior to or
      after RB irradiation. It is concluded that most of the light emission is due to
      formation of excited states generated in the decomposition of peroxides and/or
      hydroperoxides accumulated during the photolysis. Experiments carried out in the
      presence of several amino acids (Cys, Met, His, Tyr and Trp) and di- and
      tripeptides suggest that peroxides (and/or hydroperoxides) of Trp residues are
      mainly responsible for the CL observed after singlet oxygen-mediated protein
      oxidation. The much weaker CL observed after the oxidation of proteins without
      Trp residues supports this conclusion. A comparison of the results obtained
      employing free Trp, Ala-Trp and Trp-Ala dipeptides, Ala-Trp-Ala tripeptide and
      Trp-containing proteins supports the conclusion that blocking the amino group of
      the Trp moiety strongly increases the efficiency of the chemiluminescent process,
      producing approximately 2.5x10(-8) photons per oxidized Trp group in Ala-Trp. A
      mechanism comprising two chemiluminescent oxidation pathways of Trp residues is
      proposed to explain the results.

PMID- 17034273
TI  - Exploring the other side of acupuncture.

PMID- 17034274
TI  - A perspective on the emergence of meditation techniques for medical disorders.

PMID- 17034275
TI  - Physicians' personal and practice use of cam therapies in a rural community in
      the southeast United States.

PMID- 17034276
TI  - Developing a reliable nematode assay.

PMID- 17034277
TI  - Women's reasons for complementary and alternative medicine use: racial/ethnic
      differences.
AB  - OBJECTIVES: Although racial/ethnic differences in the prevalence of complementary
      and alternative medicine (CAM) utilization have been documented, differences in
      the reasons for using CAM have not been empirically assessed. In an increasingly
      diverse society, understanding differences in rates of and reasons for CAM use
      could elucidate cultural and social factors of health behaviors and inform health
      care improvements. The current study examines reasons for CAM use among women in
      four racial/ethnic groups. DESIGN: A national telephone survey of 3172 women aged
      18 years and older was conducted in four languages. Respondents were asked about
      their use of remedies or treatments not typically prescribed by a medical doctor.
      This study focuses on those women who used CAM in the previous year and their
      reasons for using CAM. RESULTS: Non-Hispanic white women were most likely to cite
      personal beliefs for CAM use. Cost of conventional medicine was most prevalent
      among Mexican-American women CAM users. Physician referral, family and friends,
      and media sources were all equally likely to lead to CAM use in non-Hispanic
      white women. In contrast, informal networks of family and friends were the most
      important social influences of CAM use among African-, Mexican-, and Chinese
      American women. CONCLUSIONS: Racial/ethnic differences in reasons for CAM use
      highlight cultural and social factors that are important to consider in public
      evaluation of the risks and benefits of CAM remedies and treatments.

PMID- 17034278
TI  - Homeopathic combination remedy in the treatment of acute childhood diarrhea in
      Honduras.
AB  - BACKGROUND: Despite the widespread availability of oral rehydration therapy,
      diarrheal illness remains a major cause of morbidity and mortality around the
      world. Previous studies have shown individualized homeopathic therapy to be
      effective in treating childhood diarrhea, but this approach requires specialized
      training. OBJECTIVE: A homeopathic combination medicine, if effective, could be
      used by health personnel on a widespread basis. METHODS: A double-blind
      randomized controlled trial was conducted in Honduras to evaluate the
      effectiveness of a homeopathic combination therapy to treat acute diarrhea in
      children. A total of 292 children with acute diarrhea was recruited; 145 were
      randomized to the experimental group and 147 to the placebo group. Tablets
      containing a combined preparation of the five most common single homeopathic
      remedies used to treat diarrhea or placebo were administered by a parent after
      each unformed stool. Children were followed up daily for 7 days or until symptoms
      resolved, whichever occurred first. Time until resolution of symptoms, daily rate
      of unformed stools, and total number of unformed stools were compared between the
      two groups. RESULTS: There was no significant difference in the likelihood of
      resolution of diarrheal symptoms between the treatment and placebo groups (hazard
      ratio = 1.02, 95% confidence interval: 0.79-1.32), with a median time until
      resolution of 3 days for both groups. Children in the treatment group had an
      average of 2.6 unformed stools per day compared to 2.8 among those in the placebo
      group; this difference was not significant (p = 0.43). The median number of
      unformed stools was 7 among children in the treatment group and 8 among those in
      the placebo group (p = 0.41). DISCUSSION: The homeopathic combination therapy
      tested in this study did not significantly reduce the duration or severity of
      acute diarrhea in Honduran children. Further study is needed to develop
      affordable and effective methods of using homeopathy to reduce the global burden
      of childhood diarrhea.

PMID- 17034279
TI  - Designing an acupuncture study: II. The nationwide, randomized, controlled German
      acupuncture trials on low-back pain and gonarthrosis.
AB  - BACKGROUND: In the nationwide German Acupuncture Trials (GERAC), verum
      acupuncture, mirroring the Traditional Chinese Medicine (TCM) acupuncture style,
      was tested against sham acupuncture and guideline standard therapy for the
      entities classified in the West as chronic low back pain (LBP) and gonarthrosis
      (GON). OBJECTIVE: The objective was to develop broadly consensual acupuncture and
      control protocols for the treatment of LBP and GON in the GERAC trials.
      METHODOLOGY: Extensive literature study and consultation with acupuncture experts
      were consulted. Personal interviews, both free and structured, e-mail
      discussions, and phone conferences were used as well. RESULTS: Broadly consensual
      acupuncture protocols for LBP and GON for verum and invasive sham acupuncture
      were developed. They included semistandardized point combinations with clearly
      described point selection rules based on TCM acupuncture diagnosis. A procedure
      was developed to help ensure homogenous treatment quality in a large multicenter
      trial. CONCLUSIONS: With 1162 randomized patients for LBP and 1039 patients for
      GON, the GERAC study design allowed acupuncture to be tested in a naturalistic
      environment. The rigorous study design and large number of physician
      investigators guaranteed a high external validity for the results. The results
      will help determine the significance of Chinese acupuncture in the context of
      Western medicine for the treatment of LBP and GON.

PMID- 17034280
TI  - The electrophysiology of de qi sensations.
AB  - OBJECTIVE: The objective was to investigate the effect of three different modes
      of stimulation on: (1) the electrical conductance of a known acupuncture point
      (AP) and a point with no known acupuncture function (NP); and (2) the
      corresponding characteristics of de qi sensations. DESIGN: The design was
      prospective. SETTINGS AND LOCATIONS: Healthy subjects were recruited for the
      study at the University of California, San Diego Medical Center. Subjects and
      Study Interventions: Fifteen subjects were enrolled. Two locations of the
      subjects' nondominant hand were marked: (1) AP (Li4); and (2) NP, a control
      location with no known acupuncture function. The following different stimulation
      paradigms were applied to the testing sites in a randomized fashion: (1)
      transcutaneous electrical stimulation via an ECG electrode; (2) manual
      stimulation via an acupuncture needle; and (3) electrical stimulation via an
      acupuncture needle. All electrical stimulation was provided at 12 V and 5 Hz for
      30 seconds. OUTCOME MEASURES: The conductance before and after each stimulation
      were measured. The subjects were asked to choose four most predominant
      descriptors of the de qi sensation after the stimulation and to rate the
      corresponding intensity on a linear VAS. RESULTS: The conductance values at the
      AP site are generally a bit higher than conductance values at the NP site for
      each given stimulation type. The de qi VAS score increased significantly after
      needle electrical stimulation (EA) in comparison to electrode or manual
      stimulation at both sites. The most predominant (incidence >30%) de qi sensation
      with electrical stimulation in either electrode or needle electrical stimulation
      was tingling, whereas in the manual stimulation, aching was the most predominant
      sensation of de qi. CONCLUSIONS: The de qi sensation appears to be qualitatively
      and quantitatively different between manual and electrical stimulation. The
      observed difference in transcutaneous electrical conductance between.

PMID- 17034281
TI  - Establishment of a discriminant mathematical model for diagnosis of deficiency
      cold syndrome using gene expression profiling.
AB  - OBJECTIVE: To screen diagnostic markers of Deficiency-Cold syndrome by gene
      expression profile and to establish a discriminant mathematical milliliters model
      for the clinical diagnosis of this syndrome based on a support vector machine
      (SVM). METHODS: A family suffering from Deficiency-Cold syndrome is chosen for
      this study. This family has 5 patients with Deficiency-Cold syndrome and 10
      normal members. The peripheral blood samples for these 5 patients and 5 normal
      members are tested by using cDNA microarray with 18,816 clones to get their
      differential expression genes. These genes are further explored to understand
      their biological functions and pathways through existing databases. A SVM model
      for clinical diagnosis is then developed based on these differential expression
      genes. RESULTS: A total of 83 differential expression genes were identified
      between patients and normal members, in which 21 genes were recorded in the
      FATIGO database and 16 genes were related to metabolism. Eight (8) pathways were
      sorted out in the KEGG database, and half pathways were associated with human
      metabolism. A discriminant mathematical model based on a support vector machine
      successfully predicted a normal person and a patient with heavy Deficiency-Cold
      syndrome based on their gene differential expression profiles. Thus, this model
      may classify the Deficiency-Cold syndrome. CONCLUSION: This work demonstrates
      that the differential expression genes can be used to identify normal persons and
      patients with Deficiency-Cold syndrome. Deficiency-Cold syndrome is mainly
      associated with the metabolism-related gene regulations. In addition, the
      discriminant mathematical model based on a support vector machine is applicable
      to the clinical diagnosis for Deficiency-Cold syndrome.

PMID- 17034282
TI  - Traditional chinese medicine for the treatment of chronic prostatitis in China: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To systematically evaluate the effectiveness of Chinese herbal
      medicine for treating chronic prostatitis (CPT) in China. DESIGN: Electronic
      medical database from China National Knowledge Infrastructure (CNKI) was
      searched, language is Chinese; date is from January 1, 1994 to December 31, 2003.
      A total of 108 trials were found, and all studies with words like "randomization"
      or "quasi-randomization" in their abstracts were included, whether they used
      blinding or not. Nineteen theses that met the entry criteria were downloaded and
      fully printed. Four groups were divided: Chinese herbs orally treated group
      (based on syndrome differentiation), Chinese herbs externally treated group,
      Chinese herbs orally and externally treated group, and integrated Western with
      Chinese herbs treated group. RESULTS: All 19 articles that met the entry criteria
      were clinical trial studies with low quality (Jadad Score <3). The results showed
      that Traditional Chinese Medicine (TCM) may benefit the patients who had CPT.
      However, from the results of the funnel plots analysis of all four groups of
      clinical trials that met the inclusion criteria in this systematic review are
      distant asymmetrical and irregular plots, which indicate that a positive
      publication bias may exist. There was no obvious evidence indicating that the
      efficacy of the therapy in the treated groups using TCM was superior to that of
      the control group (Western medicine treatment group). CONCLUSIONS: All of the
      four groups in the clinical trials have not provided evidence of evidence-based
      medicine (EBM) A class (including 1a, 1b, 1c level), failed to prove that the TCM
      may have beneficial effects for patients with CPT, because of low quality in all
      the trials and a positive publication bias. Therefore, in light of some positive
      outcomes, a good design of multicentered, randomized, parallel-controlled and
      blinding trials is needed in order to make further studies, and deserve further
      examination for the treatment of CPT with TCM.

PMID- 17034283
TI  - Clinical studies of immunomodulatory activities of Yunzhi-Danshen in patients
      with nasopharyngeal carcinoma.
AB  - OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a prevalent tumor in Hong Kong. The
      immune system of such patients could be adversely affected during the course of
      conventional chemotherapy or radiotherapy. We investigated the immunomodulatory
      effects of Traditional Chinese Medicine (TCM) Yunzhi-Danshen capsules in NPC
      patients treated with radiotherapy. DESIGN: Randomized, double-blind, placebo
      controlled 16-week study. SETTING/LOCATION: The Prince of Wales Hospital, the
      Chinese University of Hong Kong, Hong Kong. SUBJECTS: Twenty-seven (27) patients
      with histologically proven NPC, at least 18 years of age. METHODS: Twenty-seven
      patients with histologically proven NPC were recruited to take Yunzhi (3.6 g
      daily) and Dangshem (1.4 g daily) in the form of 12 combination capsules (TCM
      group) or placebo (12 capsules) daily for 16 weeks, respectively. Flow cytometry
      was used to assess the percentages and absolute counts of human lymphocyte
      subsets in whole blood. Plasma concentration of soluble interleukin-2 receptor
      and soluble tumor necrosis factor receptor 2 was measured by enzyme-linked
      immunosorbent assay (ELISA). Ex vivo production of tumor necrosis factor-alpha,
      interleukin (IL)-6, and IL-10 in the whole blood assay culture supernatant was
      measured by ELISA. RESULTS: The decreases in percentage and absolute count of T
      lymphocytes in the TCM group were less than those in the placebo group after they
      took the capsules for 16 weeks (both p < 0.05). Furthermore, the decreases in
      absolute count of T suppressor cells plus cytotoxic T lymphocytes, and T helper
      cells in the TCM group were significantly lower than those in the placebo group
      after they took the capsules for 16 weeks (both p < 0.05). CONCLUSION: These
      results suggest that Yunzhi-Danshen can exert an immunomodulating effect in
      alleviating lymphopenia during radiotherapy in NPC patients.

PMID- 17034284
TI  - Comparative studies of various ganoderma species and their different parts with
      regard to their antitumor and immunomodulating activities in vitro.
AB  - OBJECTIVES: Ganoderma lucidum (Lingzhi or Reishi) has been commonly suggested in
      East Asia as a potential candidate for prevention and treatment of different
      diseases, including cancer. Ganoderma extracts, in particular Ganoderma lucidum
      (extracts or isolated components), have previously been shown to possess
      antitumor activities. The present study aimed at comparing three different
      species of Ganoderma, wildly grown versus cultivated, as well as the different
      parts of the fruiting body (whole fruiting body, pileus, and stipe), with regard
      to their antitumor effects in human breast cancer cells and immunomodulatory
      activities in mouse splenic lymphocytes in vitro. METHODS: The aqueous extracts
      (12.5-400 microg/mL) of G. lucidum, G. sinense, and G. tsugae were examined for
      their antiproliferative activities in human breast cancer cell lines, MCF-7 and
      MDA-MB-231, as well as in normal human mammary epithelial cells (primary
      culture). The immunomodulatory effects of the extracts were evaluated in mouse
      splenic lymphocytes. The proliferative responses of the mentioned cell types were
      determined by MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide]
      assay. RESULTS: The present results demonstrated that the extracts of all tested
      Ganoderma samples could significantly inhibit cell proliferation in human breast
      cancer cell lines MCF-7 and MDA-MB-231, with G. tsugae being the most potent. The
      extracts, however, did not exert any significant cytotoxic effect on human normal
      mammary epithelial cells. Within the species G. sinense, the inhibitory effects
      of wildly grown samples were not significantly different from those of the
      cultivated samples, except at 400 microg/mL. Most of the tested extracts of
      Ganoderma stimulated mouse splenic lymphocytes proliferation. The extracts from
      the stipes of the G. tsugae and wildly grown G. sinense showed much stronger
      inhibitory effects than the other parts of the fruiting body in both cancer cell
      lines, whereas the extracts from the stipes of G. lucidum and wildly grown G.
      sinense showed stronger immunopotentiating activities in mouse splenic
      lymphocytes. CONCLUSIONS: These results indicate that the aqueous extracts of
      these commonly available Ganoderma fruiting bodies, G. lucidum, G. sinense, and
      G. tsugae have antitumor activities in human breast cancer cells and
      immunomodulatory activities in murine lymphocytes. In addition, the present
      findings also suggest that the stipes of fruiting bodies of Ganoderma species
      should be included in the preparation of extract of these fungi in order to
      obtain the most comprehensive active ingredients. To the best of the authors'
      knowledge, this is the first detailed comparison among the different parts of the
      fruiting bodies of Ganoderma.

PMID- 17034285
TI  - Consulting a complementary and alternative medical practitioner: a systematic
      inventory of motives among French patients.
AB  - OBJECTIVES: To classify people's motives for seeking care from complementary and
      alternative medicine practitioners. Participants were asked about a wide variety
      of motives representing all eight motivational states described in Reversal
      Theory (RT): telic, paratelic, conformist, negativist, mastery, sympathy, autic,
      and alloic. DESIGN: Data from a convenience sample of 256 participants was
      examined using factorial techniques. RESULTS: Six factors were evidenced that
      were easily interpretable in the RT framework. Participants perceived their
      motives largely in terms of goals and means, and within this domain they focused
      more on the goals (i.e., telic motives were more important than paratelic ones).
      Paratelic motives were, however, not unimportant: they ranked third. Participants
      also perceived their motives in terms of rules and constraints, and within this
      domain they focused more on rules (i.e., conformist motives were more important
      than negativist ones). Participants, finally, perceived their motives in terms of
      the combined domains of relationships and exchanges with others, namely, acting
      out of concern for others (alloic sympathy) as well as for themselves (autic
      mastery). CONCLUSIONS: If the six-factor structure is proved applicable, the six
      corresponding subscales could be used for systematically comparing motives among
      different types of patients, regarding different types of therapies, and among
      patients from different cultures.

PMID- 17034286
TI  - Quality of life in patients treated with Kampo medicine: a complementary
      alternative to modern medicine.
AB  - OBJECTIVE: Kampo (Japanese traditional herbal medicine) is widely used as a
      complementary medicine for improving the quality of life (QOL) of patients in
      Japan. We investigated the efficacy of kampo therapy in improving QOL of patients
      with various diseases and disorders, using the World Health Organization Quality
      of Life Brief Scale (WHOQOL-BREF). DESIGN, SETTING, AND PARTICIPANTS: One hundred
      and sixty-seven outpatients with various diseases or disorders wishing to receive
      kampo therapy and who had already been treated with modern medicines were
      recruited into the study. Patients were offered kampo formulas and modern
      medicines for 3 months. MAIN OUTCOME MEASURES: Scores of WHOQOL-BREF and Clinical
      Global Impression (CGI) Global Improvement scale, and adverse events. RESULTS:
      Eleven patients were "very much improved," 46 were "much improved," 59 were
      "minimally improved," 42 showed "no change," 7 were "minimally worse," and one
      was "much worse" in the CGI Global Improvement scale. The mean WHOQOL-BREF score
      improved significantly from 3.05 +/- 0.54 at baseline to 3.14 +/- 0.53 after 3
      months (p = 0.002). CONCLUSION: Patients presenting with various diseases and
      disorders were successfully treated with kampo therapy. Our results suggest that
      kampo therapy as a complementary medicine may improve the QOL of patients with
      various diseases and disorders.

PMID- 17034287
TI  - Use of complementary and alternative medicine among adults with chronic diseases:
      United States 2002.
AB  - BACKGROUND: Use of Complementary and Alternative Medicine (CAM) has increased in
      recent years. OBJECTIVE: The aim of this study was to determine the use of CAM
      among people with diagnosed chronic diseases. DESIGN: Cross-sectional analysis
      was used. SETTING: The 2002 National Health Interview Survey was the setting.
      PATIENTS: Participants were representative of the noninstitutionalized U.S.
      population 18 years and older. MEASUREMENTS: Respondents answered questions about
      use of CAM and physician-diagnosed arthritis, cancer, cardiovascular disease,
      diabetes, and lung disease. RESULTS: Adults with diagnosed chronic diseases are
      more likely to use CAM compared to adults with none of the reported chronic
      diseases. Adults with arthritis alone were most likely to report ever use of CAM
      (59.6%) followed by adults with cancer or lung disease alone or two or more
      chronic diseases (55%), adults with cardiovascular disease (46.4%), and adults
      with no chronic diseases (43.6%) and diabetes alone (41.4%). Adults with chronic
      diseases were also more likely to report use of CAM in the past 12 months (32% to
      43.3%), followed by adults with none of these chronic diseases (32%), and adults
      with diabetes alone (26.2%). Less than 30% of CAM users in the past 12 months
      reported talking to their healthcare professional about CAM use. LIMITATIONS:
      Information about CAM use is based on self-report. CONCLUSIONS: Use of CAM,
      particularly biologically based CAM therapies, is common and is more likely to be
      used by those with chronic diseases.

PMID- 17034288
TI  - Effects of contralateral electroacupuncture on brain function: a double-blind,
      randomized, pilot clinical trial.
AB  - OBJECTIVES: The aim of this study was to ascertain the effects of contralateral
      acupuncture on brain function using blind-spot mapping. DESIGN AND PARTICIPANTS:
      Forty (40) healthy volunteers in whom the right-side blind spot was larger than
      the left-side one-which indicates lower left-brain function-were randomly
      assigned into the following two groups in which electroacupuncture was applied
      to: (1) the contralateral ST36 acupuncture point (right side), and (2) the
      ipsilateral ST36 acupuncture point (left side). OUTCOME MEASURE: Blind-spot
      perimetry length was the outcome measure. RESULTS: Electroacupuncture to the
      contralateral side decreased the blind-spot perimetry length by 5.0 (-9.3 to 0.9)
      [median (interquartile range, IQR)], whereas that to the ipsilateral side
      increased the length by 4.5 (-3.7 to 7.8) [median, IQR]. There was significant
      difference in this length between the two groups (p < 0.05). CONCLUSIONS: These
      results suggest that electroacupuncture application increased or decreased the
      brain function- as assessed by changes to the blind spot-depending on the
      treatment side: Contralateral-side treatment has a better effect than ipsilateral
      side treatment on brain function. However, further randomized studies that
      include both right- and left-side-enlarged subjects with a sham needle are needed
      to convincingly show the effects of contralateral acupuncture on brain function.

PMID- 17034289
TI  - Systematic review of the efficacy of meditation techniques as treatments for
      medical illness.
AB  - BACKGROUND: Meditative techniques are sought frequently by patients coping with
      medical and psychological problems. Because of their increasingly widespread
      appeal and use, and the potential for use as medical therapies, a concise and
      thorough review of the current state of scientific knowledge of these practices
      as medical interventions was conducted. PURPOSE: To systematically review the
      evidence supporting efficacy and safety of meditative practices in treating
      illnesses, and examine areas warranting further study. Studies on normal healthy
      populations are not included. METHODS: Searches were performed using PubMed,
      PsycInfo, and the Cochrane Database. Keywords were Meditation, Meditative Prayer,
      Yoga, Relaxation Response. Qualifying studies were reviewed and independently
      rated based on quality by two reviewers. Mid-to-high-quality studies (those
      scoring above 0.65 or 65% on a validated research quality scale) were included.
      RESULTS: From a total of 82 identified studies, 20 randomized controlled trials
      met our criteria. The studies included 958 subjects total (397 experimentally
      treated, 561 controls). No serious adverse events were reported in any of the
      included or excluded clinical trials. Serious adverse events are reported in the
      medical literature, though rare. The strongest evidence for efficacy was found
      for epilepsy, symptoms of the premenstrual syndrome and menopausal symptoms.
      Benefit was also demonstrated for mood and anxiety disorders, autoimmune illness,
      and emotional disturbance in neoplastic disease. CONCLUSIONS: The results support
      the safety and potential efficacy of meditative practices for treating certain
      illnesses, particularly in nonpsychotic mood and anxiety disorders. Clear and
      reproducible evidence supporting efficacy from large, methodologically sound
      studies is lacking.

PMID- 17034294
TI  - Vascular endothelial growth factor-D is increased in serum of patients with
      lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease
      characterized by an abnormal proliferation of smooth muscle-like cells (LAM
      cells) in the lung and along the axial lymphatics. LAM demonstrates a
      heterogeneous clinical course, but there is no serum surrogate marker available
      for assessing the disease severity or predicting the disease progression. Since
      the authors have recently demonstrated the extensive LAM-associated
      lymphangiogenesis and its potential role in progression and metastasis of LAM
      cells, they hypothesized that serum levels of lymphangiogenic growth factors
      might be increased in LAM and become a surrogate marker for disease severity.
      METHODS AND RESULTS: VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM
      were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly
      increased in LAM patients as compared with age- and gender-matched healthy
      volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4
      approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p<0.0001).
      Serum VEGF-D levels negatively correlated with variables of pulmonary function
      tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity)
      (r=-0.365, p<0.05) and %DLco/VA (the percentage of diffusing capacity for carbon
      monoxide/alveolar volume to the predicted value) (r=-0.560, p<0.001). As
      expected, the group who received hormone therapy showed more deteriorated
      pulmonary function with higher serum VEGF-D levels than the group who was just
      observed without hormone therapy. Immunohistochemical examination of lung
      specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D.
      CONCLUSION: Serum VEGF-D levels may be a valuable surrogate marker for evaluating
      the disease severity in LAM.

PMID- 17034293
TI  - Molecular profile and proliferative responses of rat lymphatic endothelial cells
      in culture.
AB  - BACKGROUND: Lymphangiogenesis plays an important role in metastasis of many solid
      tumors. To study lymphangiogenesis under controlled conditions, an in vitro model
      is needed. The goal of this work was to establish such an in vitro model by
      determining a molecular profile of rat mesenteric lymphatic endothelial cells
      (RMLEC) and characterizing their proliferative responses to angiogenic and
      lymphangiogenic factors, such as vascular endothelial growth factor A and C (VEGF
      A and VEGF-C). METHODS AND RESULTS: RMLEC strongly expressed most lymphatic
      specific markers, including Prox-1, LYVE-1, and VEGFR-3. Proliferation of RMLEC
      was serum and heparin dependent. In the presence of low (2%) serum concentration,
      exogenously added VEGF-A and VEGFC stimulated RMLEC in a linear and dose
      dependent manner. This effect was abrogated by anti-VEGF-A and VEGF-C antibodies,
      as well as by soluble Tie-2 and Flt-4 fusion proteins. Abrogation was reversed by
      VEGF-A, suggesting that this factor as an important regulator of
      lymphangiogenesis. CONCLUSIONS: Cultured RMLEC preserved a molecular profile
      consistent with the phenotype of lymphatic endothelium in vivo and respond to
      either VEGF-A or VEGF-C factors. VEGFA was able to rescue RMLEC proliferation
      inhibited by a neutralizing VEGF-C antibody or soluble Tie-2 fusion protein.
      These results support the existence of cross-talk among angiogenic and
      lymphangiogenic factors. This work established experimental conditions that allow
      in vitro modeling of lymphatic endothelial responses to lymphangiogenic
      regulators. Preliminary results using this model suggest that VEGF-A, VEGF-C, and
      angiopoietins work in concert to promote lymphangiogenesis in vivo.

PMID- 17034295
TI  - Validation of a new technique for the quantitation of edema in the experimental
      setting.
AB  - BACKGROUND: An inherent limitation to the study of in vivo animal models of
      lymphedema is the potential inaccuracy or unreliability of existing methods for
      the quantification of edema volume as a surrogate functional measure of lymphatic
      transport capacity. Circumference-based techniques have been proposed and
      validated as a suitable alternative to volume displacement measurements in human
      clinical studies; accordingly, we have elaborated a new application of this
      approach that can be applied to small animal studies. METHODS: Acute postsurgical
      lymphedema was created experimentally in the murine tail. Both normal and
      lymphedematous murine tails were examined. Tail volume was quantitated both by
      water displacement and by a digital photographic technique. In selected mice,
      after sacrificed on postsurgical day 7, a 6 cm segment was resected from the
      midportion of the tail and cauterized to create a closed space. Known incremental
      volumes of saline (20-100 microL) were injected for subsequent digital
      photographic volumetry. RESULTS: The coefficients of variation for volume
      assessment by water displacement and by digital imaging were 0.08+/-0.09 and
      0.01+/-0.009, respectively. The two techniques were poorly correlated: while
      serial water displacement analysis yielded highly variable measurements within
      the same tail, concurrent digital imaging of the tail circumference was quite
      reproducible. Furthermore, after parenteral injection of known incremental
      volumes of saline, the correlation between the injectate volumes and the
      digitally measured increases in volume was high, both in the normal and the
      lymphedematous tail. CONCLUSION: In the murine tail, when compared to water
      displacement volumetry, digital photography yields highly reproducible data. We
      can conclude that the lack of correlation between the two methods, with the
      relatively flat slope of the linear regression relationship, reflects inherent
      inaccuracies of the water displacement method.

PMID- 17034296
TI  - Lymphoscintigraphy to evaluate the effect of high versus low intensity upper body
      dynamic exercise on lymphatic function in healthy females.
AB  - BACKGROUND: Little is known about the acute effects of exercise on the lymphatic
      system. Thus, the purpose was to determine the effect of low versus high
      intensity upper body exercise on lymphatic function in healthy females. METHODS
      AND RESULTS: On separate days, eight females performed either HI: 12 repeated
      sets of arm cranking for 2.5 min at 0.6 W.kg-1, followed by 2.5 min of rest; or
      LO: 12 repeated sets of arm cranking for 2.5 min at 0.3 W.kg-1, followed by 2.5
      min of rest. One min spot views were taken with a gamma-radiation camera
      immediately after injection of 99mTc-antimony colloid and every 10 min thereafter
      to measure the clearance rate (CR) from the first and fourth finger-web of each
      hand. Radiopharmaceutical uptake in the axillary regions (AX) at 65 min
      postinjection was also measured. Clearance from the injection sites was linear
      and expressed as a slope (% administered activity.min-1). HI resulted in
      significantly greater CR (-0.24%.min-1+/-0.06) than LO (-0.19%.min-1+/-0.05;
      p=0.003). A similar trend was seen in AX (HI: 6.3%+/-1.6, LO: 4.8%+/-1.1,
      p=0.004). CONCLUSIONS: The results indicate that an arm cranking protocol of
      higher intensity is more effective in promoting lymphatic clearance from the
      hand. Further, the high intensity protocol may be useful in the functional
      evaluation of the lymphatic system in breast cancer survivors and warrants
      further investigation.

PMID- 17034297
TI  - Literature watch. Emerging roles of the Angiopoietin-Tie and the ephrin-Eph
      systems as regulators of cell trafficking.

PMID- 17034300
TI  - Generating monodisperse pharmacological aerosols using the spinning-top aerosol
      generator.
AB  - Pharmacological aerosols of precisely controlled particle size and narrow
      dispersity can be generated using the spinning-top aerosol generator (STAG). The
      ability of the STAG to generate monodisperse aerosols from solutions of raw drug
      compounds makes it a valuable research instrument. In this paper, the versatility
      of this instrument has been further demonstrated by aerosolizing a range of
      commercially available nebulized pulmonary therapy preparations. Nebules of
      Flixotide (fluticasone propionate), Pulmicort (budesonide), Combivent (salbutamol
      sulphate and ipratropium bromide), Bricanyl (terbutaline sulphate),
      Atrovent(ipratropium bromide), and Salamol (salbutamol sulphate) were each mixed
      with ethanol and delivered to the STAG. Monodisperse drug aerosol distributions
      were generated with MMADs of 0.95-6.7 microm. To achieve larger particle sizes
      from the nebulizer drug suspensions, the STAG formed compound particle
      agglomerates derived from the smaller insoluble drug particles. These compound
      agglomerates behaved aerodynamically as a single particle, and this was verified
      using an aerodynamic particle sizer and an Andersen Cascade Impactor. Scanning
      electron microscope images demonstrated their physical structure. On the other
      hand using the nebulizer drug solutions, spherical particles proportional to the
      original droplet diameter were generated. The aerosols generated by the STAG can
      allow investigators to study the scientific principles of inhaled drug deposition
      and lung physiology for a range of therapeutic agents.

PMID- 17034301
TI  - In vitro validation of 99mTc-HFA-FP delivered via pMDI-spacer.
AB  - The purpose of the study was to label Flixotide (fluticasone propionate [FP] with
      HFA propellant), with technetium-99m and validate that (99m)Tc acts as a suitable
      marker for FP when delivered via pMDI-spacer. Sodium pertechnetate was mixed with
      5 mL of butanone. (99m)Tc was extracted into butanone and transferred into an
      empty canister. The (99m)Tc lined canister was heated, and the butanone
      evaporated to dryness. A supercooled commercial Flixotide canister was decrimped,
      and the contents transferred to the (99m)Tc lined canister and recrimped. The
      particle size distribution of FP and (99m)Tc from 10 radiolabeled canisters was
      measured using an Anderson cascade impactor calibrated to 28.3 L/min, and
      compared to commercial FP. The drug (FP) content of each particle size fraction
      was measured using ultraviolet spectrophotometry and the (99m)Tc level in each
      fraction was measured using an ionization chamber. The percentage of particles in
      the fine particle fraction (<;4.7 microm) and the percentage of (99m)Tc from
      commercial and radiolabeled canisters were compared. The mean (SD) % FP in the
      fine particle fraction, before and after label was 43.2 (1.8) % and 43.9 (2.6) %,
      respectively. The mean (SD) % (99m)Tc in the fine particle fraction was 42.1
      (5.1) %. The mean %FP exiting spacer at (<4.7 microm) before labeling was not
      significantly different from the mean % FP exiting spacer at (<4.7 microm) after
      labeling (p > 0.05). The mean % (99m)Tc attached to particles at (<4.7 microm)
      after radiolabeling was not significantly different from the mean % FP levels (p
      > 0.05). The validation in this study indicates that (99m)Tc can act as a
      suitable marker for HFAFP, delivered via pMDI-spacer.

PMID- 17034302
TI  - Comparison of SPECT aerosol deposition data with twenty-four-hour clearance
      measurements.
AB  - Three-dimensional (3D) radionuclide imaging provides detailed information on the
      distribution of inhaled aerosol material within the body. Analysis of the data
      can provide estimates of the deposition per airway generation. Information on
      regional distribution of deposited aerosol can also be obtained from 24-hour
      clearance measurements. In this study, a nebulizer was used to deliver a
      radiolabeled aerosol to nine human subjects. Single photon emission computed
      tomography (SPECT) has been used to assess the distribution of aerosol deposition
      per airway generation. The deposition pattern was also estimated using
      measurements of the aerosol remaining in the lung 24 h after inhalation. The
      error in the SPECT value was assessed by simulation and that in the 24-h
      clearance value by repeat analysis. The mean fraction of lung deposition in the
      conducting airway (CADF) from SPECT was 0.21. The corresponding 24-h clearance
      value was 0.23. These values were not significantly different. There was a weak
      but non-significant correlation between the SPECT and 24-h measurements (r =
      0.49). The standard error of the difference was 0.11. The corresponding errors on
      the SPECT and 24-h clearance measurements were 0.04 and 0.05, respectively. There
      was no systematic difference between the values of conducting airways deposition
      obtained from 24-h measurements and SPECT. However, there were random differences
      on individual subjects, which were larger than the estimated measurement errors.

PMID- 17034303
TI  - Comparison of SPECT aerosol deposition data with a human respiratory tract model.
AB  - Three-dimensional (3D) radionuclide imaging provides detailed information on the
      distribution of inhaled aerosol material within the body. Analysis of the data
      can provide estimates of the deposition per airway generation. In this study, two
      different nebulizers have been used to deliver radiolabeled aerosols of different
      particle size to 12 human subjects. Medical imaging has been used to assess the
      deposition in the body. The deposition pattern has also been estimated using the
      International Commission on Radiological Protection (ICRP) empirical model and
      compared to values obtained by experiment. The results showed generally good
      agreement between model and experiment for both aerosols for the deposition in
      the extrathoracic and conducting airways. However, there were significant
      differences in the fate of the remainder of the aerosol between the amount
      deposited in the alveolar region and that exhaled. The inter-subject variability
      of deposition predicted by the model was significantly less than that measured,
      for all regions of the body. The model predicted quite well the differences in
      deposition distribution pattern between the two aerosols. In conclusion, this
      study has shown that the ICPR model of inhaled aerosol deposition shows areas of
      good agreement with results from experiment. However, there are also areas of
      disagreement, which may be explained by hygroscopic particle growth and
      individual variation in airway anatomy.

PMID- 17034304
TI  - Aerosol deposition in the upper airways of a child.
AB  - In a small child, normally only a small amount of inhaled aerosol particles
      reaches the lungs because the majority deposits in the upper airways. In this
      study, the upper airways of a 9- month-old child, based on computed tomography
      (CT) data, are modeled to serve as input for a computational fluid dynamics
      package (CFX). Verification of the validity of aerosol deposition calculations by
      this package is accomplished by evaluating two test cases, which also can be
      solved analytically. The numerically found sedimentation fraction in a
      horizontally placed straight pipe shows deviations from the exact solution for
      small particle sizes (less than 3 micron) due to small velocities generated by
      the use of an unstructured mesh. Although these velocities are small compared to
      the mainstream velocity, they are comparable with the terminal settling velocity
      of such a particle. Also the test case for inertial impaction in a bend pipe
      demonstrated the same problem. With this in mind, the aerosol deposition of 3.7
      micron particles in the upper airway model of the child (SAINT-model) was
      calculated. Results were compared with experimentally found results in the
      literature. For small tidal volumes and flow rates, the computational results
      matched the experimentally measured results. However, large deviations were found
      for higher flow rates and small particle sizes. Most probably the incompletely
      modeled entrance at the nose and inertial effects due to turbulence might be
      responsible.

PMID- 17034305
TI  - Improving prediction of aerosol deposition in an idealized mouth using large-Eddy
      simulation.
AB  - Monodisperse aerosol deposition in an idealized mouth geometry with a relatively
      small inlet diameter (D (in) = 3.0 mm) was studied numerically using a standard
      Large Eddy Simulation (LES). A steady inhalation flow rate of Q = 32.2 L/min was
      used. Thousands of particles (2.5, 3.7, and 5.0 microm in diameter and rho (f) =
      912.0 kg/m(3) density) were released separately in the computational domain and
      aerosol deposition was determined. The total aerosol deposition results in this
      idealized mouth were in relatively good agreement when compared with measured
      data obtained in separate experiments, showing considerable improvement over the
      standard RANS/EIM (Reynolds Averaged Navier-Stokes/Eddy Interaction Model)
      approach.

PMID- 17034306
TI  - Analysis of particle deposition in the turbinate and olfactory regions using a
      human nasal computational fluid dynamics model.
AB  - The human nasal passages effectively filter particles from inhaled air. This
      prevents harmful pollutants from reaching susceptible pulmonary airways, but may
      leave the nasal mucosa vulnerable to potentially injurious effects from inhaled
      toxicants. This filtering property may also be strategically used for aerosolized
      nasal drug delivery. The nasal route has recently been considered as a means of
      delivering systemically acting drugs due to the large absorptive surface area
      available in close proximity to the nostrils. In this study, a computational
      fluid dynamics (CFD) model of nasal airflow was used with a particle transport
      and deposition code to predict localized deposition of inhaled particles in human
      nasal passages. The model geometry was formed from MRI scan tracings of the nasal
      passages of a healthy adult male. Spherical particles ranging in size from 5 to
      50 microm were released from the nostrils. Particle trajectories and deposition
      sites were calculated in the presence of steady-state inspiratory airflow at
      volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and
      olfactory region were defined in the CFD model so that particles depositing in
      these regions could be identified and correlated with their release positions on
      the nostril surfaces. When plotted against impaction parameter, deposition
      efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%,
      respectively. Analysis of preferential deposition patterns and nostril release
      positions under natural breathing scenarios can be used to determine optimal
      particle size and flow rate combinations to selectively target drug particles to
      specific regions of the nose.

PMID- 17034307
TI  - Inhaled particle deposition in unsteady-state respiratory flow at a numerically
      constructed model of the human larynx.
AB  - To evaluate the clinical effectiveness of aerosol therapy for the lower and upper
      respiratory airways, particle deposition at the human laryngeal region has been
      analyzed with various unsteady-state respiratory flow-patterns. The flow profiles
      and trajectory of aerosol particles were calculated by 3-D thermo-fluid analysis
      of a finite volume method (FVM) with 8-CPUs parallel computational system. A
      reconstructed physical model of the real laryngeal airways was modified from 3-D
      CAM modeling function of Rhinoceros based on the images of Magnetic Resonance
      Imaging (MRI). By using 104 MRI images taken vertically and horizontally at
      intervals of 2 mm on the oral cavity and the pharynx-larynx respectively, 3-D
      physical model of the laryngeal airways was obtained. The numerical results of
      flow profile analyzed by the unsteady-state respiration model showed that vortex
      flow was occurred with time at near larynx, showing uniform flow profile in both
      the oral cavity and upper side of pharynx. The vortex was appeared at the
      anterior part of the epiglottis and downward of the vocal cord. However, it was
      confirmed that few particles deposit in the vocal cord. In these cases, the
      particle deposition was taken place mostly at the oral cavity and the oropharynx.
      On the other hand, the relationship between the particle deposition efficiency
      and the impaction in the laryngeal region was well agreement with the data sets
      of ICRP task group (1993) for the larynx deposition.

PMID- 17034308
TI  - Characterization of regional and local deposition of inhaled aerosol drugs in the
      respiratory system by computational fluid and particle dynamics methods.
AB  - The present work describes the local deposition patterns of therapeutic aerosols
      in the oropharyngeal airways, healthy and diseased bronchi and alveoli using
      computational fluid and particle dynamics techniques. A user-enhanced
      computational fluid dynamics commercial finite- volume software package was used
      to compute airflow fields, deposition efficiencies, and deposition patterns of
      therapeutic aerosols along the airways. Adequate numerical meshes, generated in
      different airway sections, enabled us to more precisely define trajectories and
      local deposition patterns of inhaled particles than before. Deposition patterns
      show a high degree of heterogeneity of deposition along the airways, being more
      uniform for nanoparticles compared to micro-particles in the whole respiratory
      system at all inspiratory flow rates. Extrathoracic and tracheobronchial
      deposition fractions of nanoparticles decrease with increasing flow rates.
      However, vice versa happens to the micron-size particles, that is, the deposition
      fraction is higher at high flow rates. Both airway constrictions and the presence
      of tumors significantly increased the deposition efficiencies compared to the
      deposition efficiencies in healthy airways by a factor ranging from 1.2 to 4.4.
      In alveoli, the deposition patterns are strongly influenced by particle size and
      direction of gravity. This study demonstrated that numerical modeling can be a
      powerful tool in the aerosol drug delivery optimization. Present results may be
      integrated in future aerosol drug therapy protocols.

PMID- 17034309
TI  - Three-dimensional computational fluid dynamics simulations of particle deposition
      in the tracheobronchial tree.
AB  - Simulation of the dynamics and disposition of inhaled particles within human
      lungs is an invaluable tool in both the development of inhaled pharmacologic
      drugs and the risk assessment of environmental particulate matter (PM). The goal
      of the present focused study was to assess the utility of three-dimensional
      computational fluid dynamics (CFD) models in studying the local deposition
      patterns of PM in respiratory airways. CFD models were validated using data from
      published experimental studies in human lung casts. The ability of CFD to
      appropriately simulate trends in deposition patterns due to changing ventilatory
      conditions was specifically addressed. CFD simulations of airflow and particle
      motion were performed in a model of the trachea and main bronchi using Fluent
      Inc.'s FIDAP CFD software. Particle diameters of 8 microm were considered for
      input flow rates of 15 and 60 L/min. CFD was able to reproduce the observed
      spatial heterogeneities of deposition within the modeled bifurcations, and
      correctly predicted the "hot-spots" of particle deposition on carinal ridges. The
      CFD methods also predicted observed differences in deposition for high-versus-low
      flow rates. CFD models may provide an efficient means of studying the complex
      effects of airway geometry, particle characteristics, and ventilatory parameters
      on particle deposition and therefore aid in the design of human subject
      experiments.

PMID- 17034310
TI  - Comparison of pharmacokinetics and vasodilatory effect of nebulized and infused
      iloprost in experimental pulmonary hypertension: rapid tolerance development.
AB  - Aerosolized iloprost has been suggested for selective pulmonary vasodilatation in
      severe pulmonary hypertension, but its pharmacokinetic profile is largely
      unknown. In perfused rabbit lungs, continuous infusion of the thromboxane mimetic
      U46619 was employed for establishing stable pulmonary hypertension. Delivery of a
      total amount of 75, 300, and 900 ng of iloprost to the bronchoalveolar space by a
      10 min-aerosolization maneuver caused a dose-dependent pulmonary vasodilatation.
      Similarly, dose-dependent appearance of iloprost in the recirculating perfusate
      was noted, with maximum intravascular concentrations of iloprost ranging at 140,
      510, and 1163 pg/mL at the same time period. Comparing pharmacokinetics and
      pharmacodynamics in a more detailed fashion, the following aspects were of
      interest. (i) The bioavailability (i.e., the percentage of aerosolized iloprost
      appearing intravascularly) decreased from 76% at the lowest to 33% at the highest
      iloprost dosage. (ii) The pulmonary vasodilatory response commenced already
      during the nebulization maneuver and preceded the perfusate entry of iloprost.
      (iii) After 3-3.5 h, the pulmonary vasodilatory response to aerosolized iloprost
      had virtually completely leveled off, whereas approximately two-thirds of the
      maximum iloprost perfusate levels were still detectable. A corresponding loss of
      vasodilatory response was also noted in experiments with continuous iloprost
      perfusion for clamping of the intravascular concentration of this prostanoid. We
      conclude that aerosolized iloprost causes dose-dependent vasodilatation and
      iloprost entry into the vascular space in a pulmonary hypertension model. Limited
      bioavailability in the higher dose range may suggest active prostanoid transport
      processes, and the early pulmonary vasodilatory response appears to be
      independent of prostanoid entry into the vessel lumen. Surprisingly, rapid
      tolerance development to the vasodilatory effect of iloprost is noted, occurring
      even with fully maintained perfusate levels of this agent.

PMID- 17034311
TI  - Peak inspiratory flow rate after methacholine challenge in asthmatic patients and
      its impact on the effect of formoterol via different inhalers.
AB  - The goal of the present study was to investigate the bronchodilating effects of 6
      and 12 microg formoterol delivered by the Turbuhaler, in comparison to salbutamol
      200 microg (metered dose inhaler) and to controls without treatment. After
      inducing acute and severe bronchial obstruction by means of methacholine
      challenge, peak inspiratory mouth flow (PIMF) was measured through a stenosis,
      simulating the internal resistance of the Turbuhaler, with the in-check device.
      In addition the relationship was studied between PIMF and clinical response in
      the 3 treatment groups. In the 176 patients methacholine caused a mean fall in
      FEV(1) of 37.1 +/- 6.9% compared to baseline. Ten minutes after bronchodilator
      inhalation, FEV(1) improved significantly in all three treatment groups. At 30
      minutes after bronchodilator administration, only the salbutamol 200 microg and
      the formoterol 12 microg groups had a significantly greater increase in FEV1 than
      controls (0.69 +/- 0.43 l and 0.66 +/- 0.37 l vs 0.38 +/- 0.32 l, p < 0.0005),
      whereas the formoterol 6 microg group showed no significant improvement (0.41 +/-
      0.38 l, p = 0.74). Thirteen patients (7.4%) did not reach a minimal PIMF of 30
      l/min through the in-check device after challenge. In the four patients in the
      formoterol 6 microg group with a PIMF below 30 l/min inhalation did not cause
      bronchodilation. In conclusion, the results demonstrate that 6 microg formoterol
      via Turbuhaler leads to less and slower onset of bronchodilation compared to the
      other groups in our setting. If patients fail to generate a PIMF of 30 l/min, 6
      microg formoterol via Turbuhaler may provide inadequate relief in a severe asthma
      attack.

PMID- 17034312
TI  - Rationale for the selection of an aerosol delivery system for gene delivery.
AB  - Genetic therapeutics show great promise toward the treatment of illnesses
      associated with the lungs; however, current methods of delivery such as jet and
      ultrasonic nebulization decrease the activity and effectiveness of these
      treatments. Extremely low transfection rates exhibited by non-complexed plasmid
      DNA in these nebulizers have been primarily attributed to poor translocation and
      loss of molecular integrity as a consequence of shear-induced degradation.
      Current research focusing on methods to increase transfection rates via the
      pulmonary delivery route has largely concentrated on the incorporation of carbon
      dioxide in the air stream to increase breath depth as well as the addition of
      cationic agents that condense DNA into compact, ordered complexes. The purpose of
      this study was to examine the impact of several classic as well as the latest
      atomization devices on the structure of non-complexed DNA. Various sizes of
      plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic
      nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied
      dramatically based upon atomization device as well as DNA size. This may explain
      the inefficiency experienced by genetic therapeutics during pulmonary delivery.
      More importantly, this suggests that the selection of an atomization device
      should consider DNA size in order to achieve optimal gene delivery to the lungs.

PMID- 17034313
TI  - Assessing a system to capture stray aerosol during inhalation of nebulized
      liposomal cisplatin.
AB  - The aim of this study was to determine the efficacy of using a high-efficiency
      particulate air (HEPA) filter air cleaning system, a demistifier, to reduce the
      potential risk of fugitive aerosol contact in health care personnel working with
      patients inhaling nebulized liposomal encapsulated SLIT (Sustained-release Lipid
      Inhalation Targeting) Cisplatin. Filters were used to sample platinum in the air
      outside the tent and from the tent's exhaust stream. Air collection was performed
      under three conditions: (1) during patient dosing (14 h of air collection); (2)
      immediately after the patient has left the demistifier tent (4 h of air
      collection); and (3) when 7 mL of drug product was nebulized to dryness in the
      tent without a patient being present. Filters were collected, and placed in an
      extraction solvent. Subsequently, the solvent was assayed for platinum content by
      inductively coupled plasma-mass spectrometry (ICP-MS). Platinum levels in the
      extraction solvent were indistinguishable from the blank controls for all
      conditions. Measured levels were below workplace exposure limits established for
      cisplatin by the Occupational Safety and Health Administration (i.e., 2 ng .
      (L(1)). In addition, the demistifier was able to effectively capture aerosolized
      SLIT Cisplatin following nebulization of 7 mL of drug product to dryness in the
      tent. The demistifier tent is effective at containing any nebulized liposomal
      encapsulated cisplatin during patient treatment. Importantly, because the tent's
      HEPA filtration system is effective at removing any nebulized liposomal
      cisplatin, the exhausted air, which is free of platinum, can be returned into the
      room with no additional ventilation precautions.

PMID- 17034314
TI  - An optimized in vitro model of the respiratory tract wall to study particle cell
      interactions.
AB  - As a part of the respiratory tissue barrier, lung epithelial cells play an
      important role against the penetration of the body by inhaled particulate foreign
      materials. In most cell culture models, which are designed to study particle-cell
      interactions, the cells are immersed in medium. This does not reflect the
      physiological condition of lung epithelial cells which are exposed to air,
      separated from it only by a very thin liquid lining layer with a surfactant film
      at the air-liquid interface. In this study, A549 epithelial cells were grown on
      microporous membranes in a two chamber system. After the formation of a confluent
      monolayer the cells were exposed to air. The morphology of the cells and the
      expression of tight junction proteins were studied with confocal laser scanning
      and transmission electron microscopy. Air-exposed cells maintained monolayer
      structure for 2 days, expressed tight junctions and developed transepithelial
      electrical resistance. Surfactant was produced and released at the apical side of
      the air-exposed epithelial cells. In order to study particle-cell interactions
      fluorescent 1 microm polystyrene particles were sprayed over the epithelial
      surface. After 4 h, 8.8% of particles were found inside the epithelium. This
      fraction increased to 38% after 24 h. During all observations, particles were
      always found in the cells but never between them. In this study, we present an in
      vitro model of the respiratory tract wall consisting of air-exposed lung
      epithelial cells covered by a liquid lining layer with a surfactant film to study
      particle-cell interactions.

PMID- 17034315
TI  - Advances in our understanding of aerosolized iloprost for pulmonary hypertension.

PMID- 17034316
TI  - Assessment of emotional reactivity produced by exposure to virtual environments
      in patients with eating disorders.
AB  - The aim of this study was to assess the usefulness of virtual environments
      representing situations that are emotionally significant to subjects with eating
      disorders (ED). These environments may be applied with both evaluative and
      therapeutic aims and in simulation procedures to carry out a range of
      experimental studies. This paper is part of a wider research project analyzing
      the influence of the situation to which subjects are exposed on their performance
      on body image estimation tasks. Thirty female patients with eating disorders were
      exposed to six virtual environments: a living-room (neutral situation), a kitchen
      with high-calorie food, a kitchen with low-calorie food, a restaurant with high
      calorie food, a restaurant with low-calorie food, and a swimming-pool. After
      exposure to each environment the STAI-S (a measurement of state anxiety) and the
      CDB (a measurement of depression) were administered to all subjects. The results
      show that virtual reality instruments are particularly useful for simulating
      everyday situations that may provoke emotional reactions such as anxiety and
      depression, in patients with ED. Virtual environments in which subjects are
      obliged to ingest high-calorie food provoke the highest levels of state anxiety
      and depression.

PMID- 17034317
TI  - Demographic, habitual, and socioeconomic determinants of Internet addiction
      disorder: an empirical study of Korean teenagers.
AB  - The objective of this study was to analyze the demographic, socioeconomic, and
      habitual causes of juvenile Internet addiction. All do not agree that Internet
      addiction disorder (IAD) is a new type of addiction, but they agree that the IAD
      phenomenon has widely spread over recent years. This is also true in Korea. For
      this study, six schools in Korea were selected to collect data: two from Seoul,
      two from suburban areas, and two from rural areas. Two hundred and forty copies
      were collected out of some 700 copies distributed. Multiple regression models
      were employed to explore significant predictors of IAD. This study showed that at
      least two out of 100 teenagers in Korea are seriously suffering from IAD and that
      approximately one out of two is exposed to a kind of IAD. The causes of IAD are
      not only associated with habitual backgrounds for use of the Internet, but also
      demographic and socioeconomic backgrounds. Therefore, it can be said that the
      development of IAD is an interactive process between juveniles' habits of using
      Internet, and their demographic and socioeconomic backgrounds. As IAD progresses,
      a single type of intervention such as parent interventions or school
      interventions does not work effectively. Multimodal interventions are required to
      provide counseling services for individuals suffering from IAD.

PMID- 17034318
TI  - Characteristics and motives of adolescents talking with strangers on the
      internet.
AB  - Despite widespread concerns about the dangers of adolescents' online
      communication with strangers, we know little about (a) which types of adolescents
      talk with strangers and (b) what motivates them to do so. Drawing on a survey
      among 412 Dutch adolescents, we found that early adolescents (12-14-year-olds)
      were most prone to talk with strangers on the internet. If adolescents
      communicated online more frequently, they less often talked with strangers on the
      internet. However, if adolescents engaged in long chat sessions, they tended to
      talk with strangers on the internet more often. In contrast to earlier research,
      introversion was not related to adolescents' tendency to talk with strangers. The
      motives of entertainment, meeting new people, and social compensation increased
      adolescents' online communication with strangers.

PMID- 17034319
TI  - Pilot study for assessing the behaviors of patients with schizophrenia towards a
      virtual avatar.
AB  - This study examined whether a virtual avatar could be perceived as a real human
      by patients with mental disease, especially schizophrenia, as well as whether a
      virtual avatar could be applied to acquiring patients' behavior characteristics
      in a short conversation situation. The virtual avatar has been used for various
      applications which need to communicate with other person or to train or educate
      by showing humanlike behavior. Recently, many researches have shown that the
      virtual avatar technology has been enhanced and the avatar could be perceived
      like real human. A virtual avatar, standing in a virtual room, was designed for
      this study. Tasks to approach, initiate a talk, and answer to avatar's questions
      was assigned to the 11 patients with schizophrenia. As behavioral parameters in
      the virtual environment, the interpersonal distance and the verbal response time
      were acquired. In addition, the Positive and Negative Syndrome Scale (PANSS) for
      patients was administered in order to investigate the relationship between
      patients' symptomatic characteristics and behavior parameters. The interpersonal
      distance was negatively correlated with the negative syndrome scale, a subscale
      of PANSS, which is consistent with previous research reporting the relationship
      between interpersonal distance and a real person's image. The verbal response
      time, however, was not correlated with any other subscale of PANSS. After
      analyzing subitems of the negative syndrome of PANSS, two positive correlations
      were found: one was with blunted affect and the other was with poor rapport. We
      concluded that the virtual avatar could be perceived as a real human by
      schizophrenic patients and the avatar could draw the schizophrenic patients'
      behavior characteristics.

PMID- 17034320
TI  - Understanding behavioral intention to participate in virtual communities.
AB  - Virtual communities are formed on the Internet and are expected to serve the
      needs of members for communication, information, and entertainment. Online
      businesses should consider virtual communities as a new market place since their
      members are current or future customers. Thus, there is a need to understand the
      determinants of member intentions to participate in virtual communities. Based on
      the extended theory of planned behavior (TPB), this study develop a research
      model to identify the attitudinal, social, and perceived behavioral control
      factors that would influence members intentions to participate in virtual
      communities. Specifically, the research model decomposes the attitude component
      into perceived usefulness, perceived ease of use and perceived trust, and the
      perceived behavioral control component into Internet self-efficacy and
      facilitating conditions. Based on a survey of 165 community members, this study
      uses structural equation modeling (SEM) approach to investigate the research
      model. The results indicate that attitude and perceived behavioral control
      significantly influence member behavioral intentions, while subjective norms do
      not. Finally, this study discusses the implications of these findings and offer
      directions for future research.

PMID- 17034321
TI  - Internet access and use among homeless and indigent drug users in Long Beach,
      California.
AB  - There has been a growing interest in using the Internet to access a variety of
      populations for prevention education and health care. It is not clear that this
      is viable for homeless and other marginalized populations. The purpose of this
      study was to describe Internet access and use among a sample of homeless and
      indigent drug users. A brief questionnaire was developed to assess computer
      ownership, use, email, and Internet access and use. Participants were recruited
      through a community-based human immunodeficiency virus (HIV) prevention program.
      265 participants completed the questionnaire. While 55% had ever used a computer
      in their lifetime, only 25% had ever owned a computer, 24% had ever had their own
      email account, 33% had access to a working computer in the last 30 days, 10% had
      sent or received email in the last 30 days, and 19% had surfed or accessed
      information on the Internet in the last 30 days. Logistic regression predicting
      lifetime use of a computer showed predictive factors of having completed high
      school (Odds Ratio [OR] = 4.5; 95% Confidence Interval [CI] = 2.41, 8.38) and
      number of days used amphetamines in the last 30 days, per 5 days of use (OR =
      1.64; 95% CI = 1.18, 2.27). Inversely related were age, per 5 years of age (OR =
      0.78; 95% CI = 0.65, 0.93) and number of days used marijuana in the last 30 days,
      per 5 days of use (OR = 0.97; 95% CI = 0.76, 0.99). Very low access and usage
      suggest that Internet-based public health education models be reexamined for this
      population. The association with amphetamine use may indicate a facilitating
      effect of amphetamine by heightening awareness and increasing wakefulness.

PMID- 17034322
TI  - Using instant messaging for Internet-based interviews.
AB  - One method of data collection that has rarely been applied online is the one-on
      one interview. Because of its widespread use, the Internet-based service instant
      messaging (IM) seems to be suitable to conduct scientific online interviews. A
      unique benefit of IM is the existence of public address books. These can be used
      both as a sampling frame and as a cross-reference to validate respondents'
      demographic data. The feasibility of IM interviews was examined in a WWW survey
      as well as in actual IM interviews that were combined with an experimental
      manipulation of the request for participation. On the basis of self-reports,
      respondent behavior, and data in the address books, the studies have demonstrated
      that the risk of receiving false data in IM interviews is small. Not only is the
      quality of the obtainable data satisfying but the contact rate, response rate,
      and retention rate as well. Moreover, the experimental test demonstrated that the
      response rate is influenced by the information provided in the chat request. On
      the basis of the study results, recommendations are given as to when and how IM
      interviews should be used as a data collection method.

PMID- 17034323
TI  - Sharing tips with strangers: exploiting gift culture in computer gaming.
AB  - The aim of this study was to look at motivations behind altruistic behavior in
      virtual communities by studying the sharing of game tips by experienced gamers.
      We examine several possible motivations (pure altruism, generalized reciprocity,
      and reputation) and qualitatively analyze tip types in terms of usefulness,
      visibility, and skill level. We found that in games that do not support a
      "performance stage" for skill demonstration, players often share game tips as a
      strategy to attract attention. To a certain degree, reciprocity can be used to
      explain small favor exchanges, but earning social reputation is often a much
      stronger motivating factor.

PMID- 17034324
TI  - Identity and intimacy crises and their relationship to internet dependence among
      college students.
AB  - In an attempt to test Kandell's proposition that internet dependents used the
      internet as a coping mechanism against underlying psychological issues, this
      study investigated the extent to which the fifth and sixth Eriksonian crises
      (identity, intimacy), were related to internet dependence (online chatting,
      gaming) among college students. Students spending more than 10 hours per week on
      chatting/gaming were classified as dependents. On the basis of a national sample
      of freshmen in Taiwan, this study found that the dependents scored significantly
      lower on most of the measures that reflected the successful resolution of the
      crises, and higher on the measures that reflected unsuccessful resolution of the
      crises. Kandell's proposition was supported.

PMID- 17034325
TI  - Personality traits as predictors of intentions to seek online information about
      STDs and HIV/AIDS among junior and senior college students in Taiwan.
AB  - The purpose of this cross-sectional study is to examine how personality traits
      such as sensation- seeking and impulsive decision-making affect Taiwanese college
      students' intentions to seek online information about sexually transmitted
      diseases (STDs) and human immunodeficiency virus/acquired immune deficiency
      syndrome (HIV/AIDS). Five hundred thirty-five (n = 535) junior and senior college
      students in Taiwan were recruited and completed self-report questionnaires. This
      study found high sensation-seekers were more likely to seek information about
      STDs and HIV/AIDS on the Internet than low sensation-seekers. Impulsive decision
      makers were less likely than rational decision-makers to seek information about
      STDs and HIV/AIDS on the Internet. These findings suggest that personality needs
      to be considered as an exploratory factor which potentially influences intentions
      to seek STD and HIV/AIDS information on the Internet among Taiwanese college
      students.

PMID- 17034326
TI  - Friend networking sites and their relationship to adolescents' well-being and
      social self-esteem.
AB  - The aim of this study was to investigate the consequences of friend networking
      sites (e.g., Friendster, MySpace) for adolescents' self-esteem and well-being. We
      conducted a survey among 881 adolescents (10-19-year-olds) who had an online
      profile on a Dutch friend networking site. Using structural equation modeling, we
      found that the frequency with which adolescents used the site had an indirect
      effect on their social self-esteem and well-being. The use of the friend
      networking site stimulated the number of relationships formed on the site, the
      frequency with which adolescents received feedback on their profiles, and the
      tone (i.e., positive vs. negative) of this feedback. Positive feedback on the
      profiles enhanced adolescents' social self-esteem and well-being, whereas
      negative feedback decreased their self-esteem and well-being.

PMID- 17034327
TI  - Head-mounted displays for clinical virtual reality applications: pitfalls in
      understanding user behavior while using technology.
AB  - The use of virtual environments with head-mounted displays (HMDs) offers unique
      assets to the evaluation and therapy of clinical populations. However, research
      examining the effects of this technology on clinical populations is sparse.
      Understanding how wearers interact with the HMD is vital. Discomfort leads to
      altered use of the HMD that could confound performance measures; the very
      measures which might be used as tools for clinical decision making. The current
      study is a post-hoc analysis of the relationship between HMD use and HMD comfort.
      The analysis was conducted to examine contributing factors for a high incidence
      of simulator sickness observed in an HMD-based driving simulator. Pearson
      correlation analysis was used to evaluate objective and subjective measures of
      HMD performance and self-reported user comfort ratings. The results indicated
      weak correlations between these variables, indicating the complexity of
      quantifying user discomfort and HMD performance. Comparison of two case studies
      detailing user behavior in the virtual environment demonstrates that selected
      variables may not capture how individuals use the HMD. The validity and
      usefulness of the HMD-based virtual environments must be understood to fully reap
      the benefits of virtual reality (VR) in rehabilitation medicine.

PMID- 17034328
TI  - Effects of a personified guide on adherence to an online program for alcohol
      abusers.
AB  - The quality of the therapeutic alliance has robust effects on the outcome of
      psychotherapy and psychopharmacologic interventions. Automated behavioral health
      programs that are being developed to increase access to mental health treatment
      are administered in the absence of direct human participation, thereby precluding
      the development of a traditional therapeutic relationship. The aim of this study
      was to develop a personified guide designed to stimulate reactions similar to
      those experienced in a therapeutic relationship, and evaluate the effect of the
      guide on adherence to and satisfaction with an online alcohol use evaluation
      program. After completing a battery of four standard questionnaires used to
      evaluate problem drinking, 288 subjects were randomized to receive feedback on
      their results in text form or via a multimedia condition involving a personified
      guide. Those who received feedback via the guide demonstrated greater levels of
      program adherence by completing more modules. Reported satisfactions levels did
      not differ between the two conditions. Encouraging the personification of an
      automated behavioral health intervention may lead to greater levels of engagement
      with the program.

PMID- 17034329
TI  - Systematic evaluation of current control devices used by people with intellectual
      disabilities in non-immersive virtual environments.
AB  - Virtual environments have a role to play in facilitating the acquisition of
      living skills in people with intellectual disabilities, improving their cognitive
      skills and providing them with entertainment. However, the currently recommended
      devices to allow navigation in and interaction with the environments are
      difficult to use. Using a methodology established in an earlier study, the study
      aims to systematically document the performance of users with the currently
      recommended devices in order to (i) inform the design of a usable control device
      or devices and (ii) act as a baseline against which they can be evaluated. 40
      people with severe intellectual disabilities aged 21-67 years used four
      environments with an equal number of sessions with the different devices being
      evaluated. Results indicate that when forward movement is provided by the
      software using the mouse for both navigation and interaction allows better
      performance both initially and after exposure than using the fire button on the
      joystick. When the user had to initiate forward movement with the navigation
      device, the joystick allowed better performance than the arrows on the keyboard.
      Preventing slippage of the joystick base would make its use much easier and it is
      suggested that separate devices are retained for navigation and interaction.

PMID- 17034330
TI  - Sexual strategies theory and Internet personal advertisements.
AB  - Sexual Strategies Theory supposes that certain characteristics--namely, physical
      attractiveness in women and dominance and the ability to provide material
      resources in men--are highly desirable to potential mates because they are
      evolutionarily advantageous. However, socially based characteristics (e.g.,
      positive personality traits, common interests) are also desirable in potential
      mates. It was predicted that people who are weaker on evolutionarily advantageous
      traits (i.e., less attractive women, less wealthy men) would emphasize
      alternative, socially desirable traits to compensate for these perceived
      deficiencies. One hundred fifty-one Internet personal advertisements were
      analyzed for attractiveness, income, mention of physical attributes, and mention
      of other positive personal characteristics. Results were generally consistent
      with predictions. In males, both wealth and attractiveness were related to
      decreased emphasis on other positive personal characteristics, while in women,
      emphasis on physical attributes (but not objectively rated physical
      attractiveness) was negatively related to emphasis on other positive personal
      characteristics.

PMID- 17034331
TI  - Internet communication: an activity that appeals to shy and socially phobic
      people?
AB  - Shyness (or social anxiety) and social phobia can be viewed as two distinct
      conditions, and this study investigates whether they are related to use of the
      Internet generally, and for communication purposes. 362 participants from two
      schools, a college and a university in the Teesside area in England were asked to
      complete Mattick and Clarke's (1998) Social Phobia (SPS) and Social Interaction
      Anxiety (SIAS) scales and also answer a questionnaire which asked them about
      their use of the Internet generally and for communication purposes. The findings
      from these suggested that social anxiety and social phobia are not highly
      associated with use of the Internet either in general, or for communication
      purposes, although minor associations with certain aspects of Internet use are
      discussed.

PMID- 17034332
TI  - Success factors in internet-based psychological counseling.
AB  - A number of special effectiveness factors of internet counseling are described,
      which represent advantages over face-to-face counseling. These factors were
      explored in a large-scale internet counseling project that ran for several years.

PMID- 17034333
TI  - An experimental study on fear of public speaking using a virtual environment.
AB  - This paper examines a necessary condition for successful exploitation of a
      virtual environment (VE) in therapeutic intervention for fear of public speaking.
      The condition is that clients experience a degree of anxiety in the VE that is
      similar to what they would have been expected to experience in a similar real
      world setting. We refer to this as a "presence" response. The experimental study
      involved 20 people who were confident public speakers and 16 who were phobic,
      assessed on a standard psychological scale. Half of each group spoke within a VE
      depicting an empty seminar room, and the other half within the same room but
      populated by a neutrally behaving virtual audience of five people. Three
      responses were measured--a questionnaire-based measure of anxiety, a measure of
      self-focused attention on somatic responses, and actual heart rate. On all
      responses, the people with phobia showed a significant increase in signs of
      anxiety when speaking to the virtual audience compared to the empty room, whereas
      the confident people did not. The result was strong in spite of the relatively
      low representational and behavioral fidelity of the virtual characters.

PMID- 17034334
TI  - Impulsive nonconformity in female chat room users.
AB  - Heavy chat room use has been associated with social isolation, introversion,
      impulse control problems, and risk taking. Such characteristics form part of the
      cluster of traits associated with schizotypy. This study used multiple regression
      to examine the relationship between age, sex, four dimensions of schizotypy, and
      frequency of reported chat room use. The only significant association with
      schizotypy was between frequency of chat room use and impulsive nonconformity
      (IN) in females. These findings may be explained by the increased risk associated
      with female chat room use.

PMID- 17034335
TI  - The appeal of violent video games to lower educated aggressive adolescent boys
      from two countries.
AB  - The objective of this study was to test the effect of individual differences on
      appeal and use of video games. Participants were 299 adolescent boys from lower
      and higher secondary schools in the Netherlands and Belgium. In general, boys
      were most attracted to violent video games. Boys that scored higher in trait
      aggressiveness and lower in empathy were especially attracted to violent games
      and spent more time playing video games than did boys lower in trait
      aggressiveness. Lower educated boys showed more appreciation for both violent and
      nonviolent games and spent more time playing them than did higher educated boys.
      The present study showed that aggressive and less empathic boys were most
      attracted to violent games. The fact that heavy users of violent games show less
      empathy and higher aggressiveness suggests the possibility of desensitization.
      Other studies have shown that playing violent games increases aggressiveness and
      decreases empathy. These results combined suggest the possibility of a violence
      cycle. Aggressive individuals are attracted to violent games. Playing violent
      games increases aggressiveness and decreases empathy, which in turn leads to
      increased appreciation and use of violent games.

PMID- 17034338
TI  - Protein-folding dynamics: overview of molecular simulation techniques.
AB  - Molecular dynamics (MD) is an invaluable tool with which to study protein folding
      in silico. Although just a few years ago the dynamic behavior of a protein
      molecule could be simulated only in the neighborhood of the experimental
      conformation (or protein unfolding could be simulated at high temperature), the
      advent of distributed computing, new techniques such as replica-exchange MD, new
      approaches (based on, e.g., the stochastic difference equation), and physics
      based reduced models of proteins now make it possible to study protein-folding
      pathways from completely unfolded structures. In this review, we present
      algorithms for MD and their extensions and applications to protein-folding
      studies, using all-atom models with explicit and implicit solvent as well as
      reduced models of polypeptide chains.

PMID- 17034339
TI  - A spectroscopist's view of energy states, energy transfers, and chemical
      reactions.
AB  - This chapter describes a research career beginning at Berkeley in 1960, shortly
      after Sputnik and the invention of the laser. Following thesis work on
      vibrational spectroscopy and the chemical reactivity of small molecules, we
      studied vibrational energy transfers in my own lab. Collision-induced transfers
      among vibrations of a single molecule, from one molecule to another, and from
      vibration to rotation and translation were elucidated. My research group also
      studied the competition between vibrational relaxation and chemical reaction for
      potentially reactive collisions with one molecule vibrationally excited. Lasers
      were used to enrich isotopes by the excitation of a predissociative transition of
      a selected isotopomer. We also tested the hypotheses of transition-state theory
      for unimolecular reactions of ketene, formaldehyde, and formyl fluoride by (a)
      resolving individual molecular eigenstates above a dissociation threshold, (b)
      locating vibrational levels at the transition state, (c) observing quantum
      resonances in the barrier region for motion along a reaction coordinate, and (d)
      studying energy release to fragments.

PMID- 17034340
TI  - The mechanistic basis of infarct healing.
AB  - Myocardial infarction triggers an inflammatory cascade that results in healing
      and replacement of the damaged tissue with scar. Cardiomyocyte necrosis triggers
      innate immune mechanisms eliciting Toll-like receptor- mediated responses,
      activating the complement cascade and generating reactive oxygen species.
      Subsequent activation of NF-kappaB is a critical element in the regulation of
      cytokine, chemokine, and adhesion molecule expression in the ischemic myocardium.
      Chemokine induction mediates leukocyte recruitment in the myocardium. Pleiotropic
      proinflammatory cytokines, such as TNF-alpha, IL-1, and IL-6, are also
      upregulated in the infarct and exert a wide range of effects on a variety of cell
      types. Timely repression of proinflammatory gene synthesis is crucial for optimal
      healing; IL-10 and TGF-beta-mediated pathways may be important for suppression of
      chemokine and cytokine expression and for resolution of the leukocytic
      infiltrate. In addition, TGF-beta may be critically involved in inducing
      myofibroblast differentiation and activation, promoting extracellular matrix
      protein deposition in the infarcted area. The composition of the extracellular
      matrix plays an important role in regulating cell behavior. Both structural and
      matricellular proteins modulate cell signaling through interactions with specific
      surface receptors. The molecular and cellular changes associated with infarct
      healing directly influence ventricular remodeling and affect prognosis in
      patients with myocardial infarction.

PMID- 17034341
TI  - Redox control of neural function: background, mechanisms, and significance.
AB  - The redox environment within neural cells is dependent on a series of redox
      couples. The glutathione disulfide/ glutathione (GSSG/GSH) redox pair forms the
      major redox couple in cells and as such plays a critical role in regulating redox
      dependent cellular functions. Not only does GSH act as an antioxidant but it also
      can modulate the activity of a variety of different proteins via S
      glutathionylation of cysteine sulfhydryl groups. The thioredoxin system also
      makes a significant contribution to the redox environment by reducing inter- and
      intrachain protein disulfide bonds as well as maintaining the activity of
      important antioxidant enzymes such as peroxiredoxins and methionine sulfoxide
      reductases. The redox environment affects the activity and function of a number
      of different protein phosphatases, protein kinases, and transcription factors.
      The sum of these effects will determine how changes in the redox environment
      alter overall cellular function, thereby playing a fundamental role in regulating
      neural cell fate and physiology.

PMID- 17034342
TI  - Oxidative stress in neurodegenerative disorders.

PMID- 17034343
TI  - Nitrosative stress, cellular stress response, and thiol homeostasis in patients
      with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and
      memory decline, personality changes, and synapse loss. Increasing evidence
      indicates that factors such as oxidative and nitrosative stress, glutathione
      depletion, and impaired protein metabolism can interact in a vicious cycle, which
      is central to AD pathogenesis. In the present study, we demonstrate that brains
      of AD patients undergo oxidative changes classically associated with a strong
      induction of the so-called vitagenes, including the heat shock proteins (HSPs)
      heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase
      (TRXr). In inferior parietal brain of AD patients, a significant increase in the
      expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased,
      compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was
      decreased in AD patients, compared with the control group, and was associated
      with a significant increase in oxidative stress markers (i.e., GSSG,
      hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes,
      we observed an increased expression of inducible nitric oxide synthase, HO-1,
      Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the
      pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1
      and TRXr, may represent important targets for novel cytoprotective strategies.

PMID- 17034344
TI  - Experimental encephalomyelitis induces changes in DJ-1: implications for
      oxidative stress in multiple sclerosis.
AB  - DJ-1 plays an important role in oxidative stress, and is involved in various
      neurodegenerative diseases. Accumulating evidence suggests a central role for
      oxidative stress in multiple sclerosis (MS). The aim of this study was to examine
      whether changes occur in DJ-1 expression in an animal model of MS, experimental
      autoimmune encephalomyelitis (EAE). We found upregulation of DJ-1 mRNA and
      protein expression levels in EAE and a correlation between disease severity and
      increased DJ-1 levels. Although DJ-1 isoforms were more alkaline in controls, in
      EAE, a shift was noted toward acidic isoforms. ROS induced by SIN-I exposure led
      to an increase in DJ-1 mRNA and protein levels in human glioma U-87 cells.
      Immunocytochemical staining demonstrated that DJ-1 is present both in the
      cytoplasm and the nuclei of these cells. This is the first report of modulation
      of DJ-1 expression in EAE. Upregulation of DJ-1 was noted in EAE, and similar
      results were observed in glioma cells exposed to ROS. In view of the accumulating
      evidence on the central role of oxidative stress in MS, and the importance of DJ
      1 in oxidative stress management by the CNS, we believe that DJ-1 will be found
      to have a central role in MS.

PMID- 17034345
TI  - Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders.
AB  - When subjected to excessive oxidative stress, neurons may respond adaptively to
      overcome the stress, or they may activate a programmed cell death pathway called
      apoptosis. Apoptosis is characterized by alterations in mitochondria and the
      endoplasmic reticulum and activation of cysteine proteases called caspases.
      Increasing evidence suggests that apoptotic biochemical cascades are involved in
      the dysfunction and death of neurons in neurodegenerative disorders such as
      Alzheimer's, Parkinson, and Huntington's diseases. Studies of normal aging, of
      genetic mutations that cause disease, and of environmental factors that affect
      disease risk are revealing cellular and molecular alterations that may cause
      excessive oxidative stress and trigger neuronal apoptosis. Accumulation of self
      aggregating proteins such as amyloid beta-peptide, tau, alpha-synuclein, and
      huntingtin may be involved in apoptosis both upstream and downstream of oxidative
      stress. Membrane-associated oxidative stress resulting in perturbed lipid
      metabolism and disruption of cellular calcium homeostasis may trigger apoptosis
      in several different neurodegenerative disorders. Counteracting neurodegenerative
      processes are an array of mechanisms including neurotrophic factor signaling,
      antioxidant enzymes, protein chaperones, antiapoptotic proteins, and ionostatic
      systems. Emerging findings suggest that the resistance of neurons to death during
      aging can be enhanced by modifications of diet and lifestyle.

PMID- 17034346
TI  - Proteasomal dysfunction: a common feature of neurodegenerative diseases?
      Implications for the environmental origins of neurodegeneration.
AB  - The neurodegenerative diseases that afflict humans affect different part of the
      nervous system and have different symptoms and prognoses, yet they have certain
      things in common. One of them is defects in the clearance of abnormal or other
      "unwanted" proteins, particularly affecting the proteasome system. In this
      review, I advance two concepts: (a) that defects in protein clearance can be a
      fundamental cause of neurodegeneration, and (b) that because proteasome
      inhibitors are widespread in nature, their ingestion may contribute to
      "spontaneous" neurodegeneration.

PMID- 17034347
TI  - Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer's
      disease: insights into mechanism of neurodegeneration from redox proteomics.
AB  - Alzheimer's disease (AD), the leading cause of dementia, involves regionalized
      neuronal death, synaptic loss, and an accumulation of intraneuronal,
      neurofibrillary tangles and extracellular senile plaques. Although the initiating
      causes leading to AD are unknown, a number of previous studies reported the role
      of oxidative stress in AD brain. Postmortem analysis of AD brain showed elevated
      markers of oxidative stress including protein nitrotyrosine, carbonyls in
      proteins, lipid oxidation products, and oxidized DNA bases. In this review, we
      focus our attention on the role of protein oxidation and lipid peroxidation in
      the pathogenesis of AD. Particular attention is given to the current knowledge
      about the redox proteomics identification of oxidatively modified proteins in AD
      brain.

PMID- 17034348
TI  - DNA oxidation in Alzheimer's disease.
AB  - Oxidative damage to DNA may play an important role in aging and neurodegenerative
      diseases such as Alzheimer's disease (AD). Attack on DNA by reactive oxygen
      species, particularly hydroxyl radicals, can lead to strand breaks, DNA-DNA and
      DNA-protein cross-linking, sister chromatid exchange and translocation, and
      formation of at least 20 oxidized base adducts. Modification of DNA bases can
      lead to mutation and altered protein synthesis. In late-stage AD brain, several
      studies have shown an elevation of the base adducts 8 hydroxyguanine (8-OHG), 8
      hydroxyadenine (8-OHA), 5-hydroxycytosine (5-OHC), and 5-hydroxyuracil, a
      chemical degradation product of cytosine. Several studies have shown a decline in
      repair of 8-OHG in AD. Most recently, our studies have shown elevated 8-OHG, 8
      OHA, and 5,6-diamino-5-formamidopyrimidine in nuclear and mitochondrial DNA in
      mild cognitive impairment, the earliest detectable form of AD, suggesting that
      oxidative damage to DNA is an early event in AD and not a secondary phenomenon.

PMID- 17034349
TI  - Reproductive hormones modulate oxidative stress in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by gradual
      cognitive decline, impairments in speech and language, and dysfunction in the
      sensorimotor systems, culminating in complete reliance on nursing care. Oxidative
      stress, caused by an imbalance in the pro-oxidant/antioxidant mechanisms in the
      body, has been implicated in AD pathogenesis, as in many other age-associated
      diseases such as atherosclerosis, Parkinson disease, and amyotrophic lateral
      sclerosis. Although the hormones estrogen, progesterone, testosterone, and
      luteinizing hormone are best known for their roles in reproduction, many studies
      show these hormones have other roles, including neuroprotection. Changes in the
      levels of these hormones that occur in reproductive senescence are hypothesized
      to increase risk of AD, as a result of reduced protection against oxidative
      insults. The Abeta peptide, overproduction of which is thought to be a key
      pathogenic event in the development of AD, is neurotoxic, most likely due to its
      ability to promote oxidative stress. The reproductive hormones are known to
      influence Abeta metabolism, and this review discusses the beneficial and
      detrimental effects these hormones have on Abeta production and oxidative stress,
      and their relevance in potential AD therapies.

PMID- 17034350
TI  - Oxidative damage in Huntington's disease pathogenesis.
AB  - Huntington's disease (HD) is a devastating neurodegenerative disorder
      characterized by the progressive development of involuntary choreiform movements,
      cognitive impairment, neuropsychiatric symptoms, and premature death. These
      phenotypes reflect neuronal dysfunction and ultimately death in selected brain
      regions, the striatum and cerebral cortex being principal targets. The genetic
      mutation responsible for the HD phenotype is known, and its protein product,
      mutant huntingtin (mhtt), identified. HD is one of several "triplet repeat"
      diseases, in which abnormal expansions in trinucleotide repeat domains lead to
      elongated polyglutamine stretches in the affected gene's protein product. Mutant
      htt-mediated toxicity in the brain disrupts a number of vital cellular processes
      in the course of disease progression, including energy metabolism, gene
      transcription, clathrin-dependent endocytosis, intraneuronal trafficking, and
      postsynaptic signaling, but the crucial initiation mechanism induced by mhtt is
      still unclear. A large body of evidence, however, supports an early and critical
      involvement of defects in mitochondrial function and CNS energy metabolism in the
      disease trigger. Thus, downstream death-effector mechanisms, including
      excitotoxicity, apoptosis, and oxidative damage, have been implicated in the
      mechanism of selective neuronal damage in HD. Here we review the current evidence
      supporting a role for oxidative damage in the etiology of neuronal damage and
      degeneration in HD.

PMID- 17034351
TI  - On the relation of oxidative stress to neuroinflammation: lessons learned from
      the G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
AB  - The central nervous system (CNS) presents both challenges and opportunities to
      researchers of redox biochemistry. The CNS is sensitive to oxidative damage
      during aging or disease; excellent transgenic models of specific
      neurodegenerative diseases have been created that reproduce oxidative stress
      components of the corresponding human disorder. Mouse models of familial
      amyotrophic lateral sclerosis (ALS) based on overexpressed mutant human Cu, Zn
      superoxide dismutase (SOD1) are cases in point. These animals experience
      predictably staged, age-dependent motor neuron degeneration with profound
      cellular and biochemical damage to nerve fibers and spinal cord tissue. Severe
      protein and lipid oxidation occurs in these animals, apparently as an indirect
      consequence of protein aggregation or cytopathic protein-protein interactions, as
      opposed to aberrant redox catalysis by the mutant enzyme. Recent studies of G93A
      SOD1 mice and rats suggest that oxidative damage is part of an unmitigated
      neuroinflammatory reaction, possibly arising in combination from mitochondrial
      dysfunction plus pathophysiologic activation of both astrocytes and microglia.
      Lesions to redox signal-transduction pathways in mutant SOD1+ glial cells may
      stimulate broad-spectrum upregulation of proinflammatory genes, including
      arachidonic acid-metabolizing enzymes [e.g., cyclooxygenase-II (COX-II) and 5
      lipoxygenase (5LOX)]; nitric oxide synthase (NOS) isoforms; cytokines
      (particularly tumor necrosis factor alpha, TNF-alpha); chemokines; and
      immunoglobulin Fc receptors (FcgammaRs). The integration of these processes
      creates a paracrine milieu inconsistent with healthy neural function. This review
      summarizes what has been learned to date from studies of mutant SOD1 transgenic
      animals and demonstrates that the G93A-SOD1 mouse in particular is a robust
      laboratory for the study of neuroinflammation and redox biochemistry.

PMID- 17034352
TI  - Oxidative stress and therapeutic approaches in HIV dementia.
AB  - Despite the rapidly increasing incidence of HIV infection worldwide and the
      increasing prevalence of HIVassociated cognitive impairment, even in patients
      adequately treated with antiretroviral therapy, currently no effective treatment
      exists for HIV dementia. A broad range of studies using either brain or
      cerebrospinal fluid (CSF) tissues from well-characterized patients with HIV
      dementia, animal models, and in vitro studies from several laboratories using HIV
      infected cells or HIV proteins provide overwhelming evidence for oxidative stress
      in mediating neuronal injury in this patient population. These studies also
      suggest that patients with apolipoprotein E (ApoE) 4 allele are more susceptible
      to such oxidative damage. In this review, we provide a critical analysis of these
      studies, including the few clinical trials that have used antioxidants to treat
      HIV dementia. We also discuss several novel agents with potent antioxidative
      properties and provide a rationale for combination antioxidant and
      neuroprotective therapy.

PMID- 17034353
TI  - Ischemic preconditioning triggers nuclear translocation of thioredoxin and its
      interaction with Ref-1 potentiating a survival signal through the PI-3-kinase-Akt
      pathway.
AB  - Thioredoxin (Trx-1), a key mediator of cellular redox homeostasis and cell
      survival, is implicated in redox signaling in the ischemic myocardium. To
      investigate further its mechanism of action, Trx expression in rat heart was
      suppressed by direct injection of small hairpin RNA against Trx-1 (shRNA-Trx-1).
      Forty-eight hours after treatment, hearts were excised for isolated working-heart
      preparation. A group of hearts was preconditioned (PC) by subjecting them to four
      cyclic episodes of 5-min ischemia, each followed by 10 min of reperfusion. All
      the hearts, PC or non-PC, were subjected to 30-min ischemia followed by 2 h of
      reperfusion. As expected, the PC hearts exhibited improved ventricular function,
      reduced infarct size, and cardiomyocyte apoptosis. Also in PC hearts, an increase
      was noted in Trx-1 and other cardioprotective and redox-regulated proteins like
      Ref-1, phospho-Akt, and NF-kappaB DNA-binding activity. PC also caused nuclear
      translocation of Trx-1 and Ref-1 followed by their association. However, in
      hearts treated with shRNA-Trx 1, the cardioprotective effects of PC were
      abolished along with a concomitant decrease in nuclear localized Trx-1 and Ref-1,
      along with a decrease in phospho-Akt and NF-kappaB. These results demonstrate
      that PC triggers translocation of Trx-1 into the nucleus, where it becomes
      associated with Ref-1 and performs redox signaling through the activation of NF
      kappaB and an increase in prosurvival signal inducer phospho-Akt.

PMID- 17034354
TI  - Oxidative stress and growth-regulating intracellular signaling pathways in
      cardiac myocytes.
AB  - The toxic effects of oxidative stress on cells (including cardiac myocytes, the
      contractile cells of the heart) are well known. However, an increasing body of
      evidence has suggested that increased production of reactive oxygen species (ROS)
      promotes cardiac myocyte growth. Thus, ROS may be 'second messenger' molecules in
      their own right, and growth-promoting neurohumoral agonists might exert their
      effects by stimulating production of ROS. The authors review the principal growth
      promoting intracellular signaling pathways that are activated by ROS in cardiac
      myocytes, namely the mitogen-activated protein kinase cascades (extracellular
      signal-regulated kinases 1/2, c-Jun N-terminal kinases, and p38-mitogen-activated
      protein kinases) and the phosphoinositide 3-kinase/protein kinase B (Akt)
      pathway. Possible mechanisms are discussed by which these pathways are activated
      by ROS, including the oxidation of active site cysteinyl residues of protein and
      lipid phosphatases with their consequent inactivation, the potential involvement
      of protein kinase C or the apoptosis signal-regulating kinase 1, and the current
      models for the activation of the guanine nucleotide binding protein Ras.

PMID- 17034355
TI  - The telomere-telomerase axis and the heart.
AB  - The preservation of myocyte number and cardiac mass throughout life is dependent
      on the balance between cell death and cell division. Rapidly emerging evidence
      indicates that new myocytes can be formed through the activation and
      differentiation of resident cardiac progenitor cells. The critical issue is the
      identification of mechanisms that define the aging of cardiac progenitor cells
      and, ultimately, their inability to replace dying myocytes. The most reliable
      marker of cellular senescence is the modification of the telomere-telomerase
      axis, together with the expression of the cell cycle inhibitors p16INK4a and p53.
      Cellular senescence is characterized by biochemical events that occur within the
      cell. In this regard, one of the most relevant processes is represented by
      repeated oxidative stress that may evolve into the activation of the cell death
      program or result in the development of a senescent phenotype. Thus, the
      modulation of telomerase activity and the control of telomeric length, together
      with the attenuation of the formation of reactive oxygen species, may represent
      important therapeutic tools in regenerative medicine and in prevention of aging
      and diabetic cardiomyopathies.

PMID- 17034356
TI  - Role of thioredoxin in cell growth through interactions with signaling molecules.
AB  - The thioredoxin system helps maintain a reducing environment in cells, but
      thioredoxin functions as more than simply an antioxidant. Thioredoxin functions
      depend on the protein's redox state, as determined by two conserved cysteines.
      Key biologic activities of thioredoxin include antioxidant, growth control, and
      antiapoptotic properties, resulting from interaction with target molecules
      including transcription factors. Mechanisms by which thioredoxin regulates cell
      growth include binding to signaling molecules such as apoptosis signal-regulating
      kinase-1 (ASK-1) and thioredoxin-interacting protein (Txnip). The molecular
      interplay between thioredoxin, ASK-1, and Txnip potentially influences cell
      growth and survival in diverse human diseases such as cancer, diabetes, and heart
      disease. In this review, we focus on the structure of thioredoxin and its
      functional regulation of cell growth through the interactions with signaling
      molecules.

PMID- 17034357
TI  - Role of reversible, thioredoxin-sensitive oxidative protein modifications in
      cardiac myocytes.
AB  - Reactive oxygen species (ROS) are important mediators of myocardial remodeling.
      However, the precise molecular mechanisms by which ROS exert their effects are
      incompletely understood. ROS induce oxidative posttranslational protein
      modifications that can regulate the function of structural, functional, and
      signaling proteins. For example, oxidative modification of free reactive thiols
      (S-thiolation) on the small G protein Ras increases Ras activity and thereby
      promotes ROS-dependent hypertrophic signaling in cardiac myocytes. By reducing
      thiols and restoring reversible thiol modifications, thioredoxin and glutaredoxin
      can act as regulators of ROS-mediated protein function. Understanding the
      regulation and functional relevance of oxidative protein modifications in
      myocardial remodeling may lead to new therapeutic strategies.

PMID- 17034358
TI  - Reactive oxygen species drives myocardial angiogenesis?
AB  - Neovascularization, the natural physiological process of formation of new blood
      vessels, is extremely important for ameliorating the function of the heart that
      undergoes ischemic stress. This process is potentially important for the
      treatment of ischemic heart and limb diseases, which includes formation of
      capillaries (angiogenesis) and collateral arteries. Ischemia or coronary artery
      occlusion induces vascular endothelial growth factor (VEGF) in the experimental
      rat myocardial infarction model, and this molecule encourages development of
      coronary collateral circulation and retention of the blood supply to the ischemic
      area. Restoration of the blood supply to the ischemic area prevents cardiomyocyte
      death and cardiac remodeling. Among the various triggers and enhancers of
      angiogenesis, hypoxic or ischemic preconditioning, as well as pharmacologic
      agents such as statin and resveratrol, have been identified as important stimuli
      for the induction of new vessel growth. It has already been demonstrated that the
      VEGF family and its receptor system is the fundamental regulator in the redox
      cell signaling of angiogenesis. This review article will focus on the role of
      reactive oxygen species in the process of myocardial angiogenesis.

PMID- 17034359
TI  - Elevated serum 8-oxo-dG in hemodialysis patients: a marker of systemic
      inflammation?
AB  - Does inflammation, as assessed by high sensitivity C-reactive protein (hs-CRP),
      in patients with end-stage renal disease (ESRD) tightly associate with increased
      serum levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8- oxo-dG)? Increased
      oxidative stress and inflammation have both been highlighted among several
      nontraditional risk factors for cardiovascular disease, which is the main cause
      of mortality in ESRD patients. In contrast to oxidative stress effects on
      proteins and lipids, DNA base damage has not been well demonstrated in ESRD. Two
      groups of hemodialysis patients were studied, one group with persistent
      inflammation (n = 13, with constant elevation of CRP > 10 mg/L for 6 months) and
      one group of noninflamed patients (n = 19, with constant CRP < 10 mg/L for 6
      months). Serum 8-oxo-dG was significantly elevated in persistent inflammation in
      comparison to noninflamed patients. At an individual level, a significant
      correlation was found between serum 8-oxo-dG and hsCRP. Extracellular 8-oxo-dG
      leads to intracellular oxidative damage on the nucleotide pool, thus providing a
      sensitive marker for inflammatory response. Serum levels of 8-oxo-dG, in
      combination with other inflammatory markers, serve as useful diagnostic tools for
      identification of patients in risk for inflammatory complications.

PMID- 17034360
TI  - 6th COSTAM/SFRR (ASEAN/Malaysia) International Workshop on Micronutrients,
      Oxidative Stress, and the Environment.
AB  - The 6(th) COSTAM/SFRR (ASEAN/Malaysia) workshop, "Micronutrients, Oxidative
      Stress, and the Environment," was held from June 29 to July 2 at Holiday Inn
      Damai Beach Resort in Kuching, Sarawak. Two hundred twenty participants from 17
      countries presented recent advances on natural antioxidants in the area of
      oxidative stress and molecular aspects of nutrition. Natural products and
      research are an important program in academic institutions and are experiencing
      unprecedented interest and growth by the scientific community and public health
      authorities. Progress is being driven by better understanding of the molecular
      mechanisms of the relation between oxidative stress and micronutrient action. The
      gathering of scientists from around the world was fruitful, and we hope that
      future work will be developed by the formal and informal interactions that took
      place in this beautiful tropical setting.

PMID- 17034361
TI  - Adiponectin inhibits superoxide generation by human neutrophils.
AB  - Adiponectin (Ad), a member of the adipocytokine family, has been reported to
      possess antiinflammatory properties. We investigated the effects of full-length
      human Ad (hAd) on phorbol 12-myristate 13-acetate (PMA)-induced O2-* generation
      by human neutrophils. hAd, even at the lowest tested concentration of 0.001
      microg/ml, after 30-min pretreatment of cells, significantly inhibited O2-*
      generation by neutrophils stimulated with PMA (100 nM). However, no relation
      between the dose of hAd and extent of inhibition of PMA-induced O2-* generation
      was observed with increasing the concentration of hAd up to 1 microg/ml. hAd also
      significantly inhibited neutrophil O2-* generation stimulated by N-formyl
      methionyl-leucyl-phenylalanine (100 microM) and diacylglycerol (500 nM), as well
      as the PMA-induced neutrophil nitroblue tetrazolium reduction and H2O2 formation.
      Pretreatment of neutrophils with pronase-digested hAd failed to inhibit the PMA
      induced O2-* generation. For the first time, this study revealed that Ad
      inhibited O2-* generation by neutrophils, possibly through regulation of NADPH
      oxidase.

PMID- 17034362
TI  - Redox control of apoptosis: an update.
AB  - The redox environment of the cell is currently thought to be extremely important
      to control cell growth, differentiation, and apoptosis as many redox-sensitive
      proteins characterize these networks. A recent, widely accepted theory is that
      free radicals are not only dangerous species but, at low concentration, they have
      been designed by evolution to participate in the maintenance of cellular redox
      (reduction/oxidation) homeostasis. This notion derives from the evidence that
      cells constantly generate free radicals both as waste products of aerobic
      metabolism and in response to a large variety of stimuli. Free radicals, once
      produced, provoked cellular responses (redox regulation) against oxidative stress
      transducing the signals to maintain the cellular redox balance. Growing evidence
      suggests that in many instances the production of radical species is tightly
      regulated and their downstream targets are very specific, indicating that
      reactive oxygen species and reactive nitrogen species actively participate in
      several cell-signalling pathways as physiological "second messengers." In this
      review, we provide a general overview and novel insights into the redox-dependent
      pathways involved in programmed cell death.

PMID- 17034364
TI  - The lipidation status of acute-phase protein serum amyloid A determines
      cholesterol mobilization via scavenger receptor class B, type I.
AB  - During the acute-phase reaction, SAA (serum amyloid A) replaces apoA-I
      (apolipoprotein A-I) as the major HDL (high-density lipoprotein)-associated
      apolipoprotein. A remarkable portion of SAA exists in a lipid-free/lipid-poor
      form and promotes ABCA1 (ATP-binding cassette transporter A1)-dependent cellular
      cholesterol efflux. In contrast with lipid-free apoA-I and apoE, lipid-free SAA
      was recently reported to mobilize SR-BI (scavenger receptor class B, type I)
      dependent cellular cholesterol efflux [Van der Westhuyzen, Cai, de Beer and de
      Beer (2005) J. Biol. Chem. 280, 35890-35895]. This unique property could strongly
      affect cellular cholesterol mobilization during inflammation. However, in the
      present study, we show that overexpression of SR-BI in HEK-293 cells (human
      embryonic kidney cells) (devoid of ABCA1) failed to mobilize cholesterol to lipid
      free or lipid-poor SAA. Only reconstituted vesicles containing phospholipids and
      SAA promoted SR-BI-mediated cholesterol efflux. Cholesterol efflux from HEK-293
      and HEK-293[SR-BI] cells to lipid-free and lipid-poor SAA was minimal, while
      efficient efflux was observed from fibroblasts and CHO cells (Chinese-hamster
      ovary cells) both expressing functional ABCA1. Overexpression of SR-BI in CHO
      cells strongly attenuated cholesterol efflux to lipid-free SAA even in the
      presence of an SR-BI-blocking IgG. This implies that SR-BI attenuates ABCA1
      mediated cholesterol efflux in a way that is not dependent on SR-BI-mediated re
      uptake of cholesterol. The present in vitro experiments demonstrate that the
      lipidation status of SAA is a critical factor governing cholesterol acceptor
      properties of this amphipathic apolipoprotein. In addition, we demonstrate that
      SAA mediates cellular cholesterol efflux via the ABCA1 and/or SR-BI pathway in a
      similar way to apoA-I.

PMID- 17034366
TI  - Developmental windows and environment as important factors in the expression of
      genetic information: a cardiovascular physiologist's view.
AB  - Genetic studies in humans and rodent models should help to identify altered genes
      important in the development of cardiovascular diseases, such as hypertension.
      Despite the considerable research effort, it is still difficult to identify all
      of the genes involved in altered blood pressure regulation thereby leading to
      essential hypertension. We should keep in mind that genetic hypertension and
      other cardiovascular diseases might develop as a consequence of early errors in
      well-co-ordinated systems regulating cardiovascular homoeostasis. If these early
      abnormalities in the ontogenetic cascade of expression of genetic information
      occur in critical periods of development (developmental windows), they can
      adversely modify subsequent development of the cardiovascular system. The
      consideration that hypertension and/or other cardiovascular diseases are late
      consequences of abnormal ontogeny of the cardiovascular system could explain why
      so many complex interactions among genes and environmental factors play such a
      significant role in the pathogenesis of these diseases. The detailed description
      and precise time resolution of major developmental events occurring during
      particular stages of ontogeny in healthy individuals (including advanced
      knowledge of gene expression) could facilitate the detection of abnormalities
      crucial for the development of cardiovascular alterations characteristic of the
      respective diseases. Transient gene switch-on or switch-off in specific
      developmental windows might be a useful approach for in vivo modelling of
      pathological processes. This should help to elucidate the mechanisms underlying
      cardiovascular diseases (including hypertension) and to develop strategies to
      prevent the development of such diseases.

PMID- 17034367
TI  - A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in
      patients with gastric carcinoma.
AB  - In order to determine the in vivo characteristics of huA33, an open label dose
      escalation biopsy-based phase I clinical trial and radioimmunolocalization study
      were conducted with a complement determinant region-grafted humanized monoclonal
      antibody against the A33 antigen in patients with gastric carcinoma. Thirteen
      patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0
      mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against
      Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical
      diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week
      prior to surgery. Adverse events were monitored, and imaging studies with gamma
      camera plus ex vivo scintigraphy of the resected specimen, biodistribution study
      by dosimetry analysis of the biopsied and resected tissues, and
      immunohistochemical analysis were carried out and evaluated. No dose-limiting
      toxicity was observed during the trial. Therefore, the maximum tolerated dose was
      not reached. Although cancer tissues with + intensity and <25% extent by
      immunostaining in biopsied frozen sections did not show positive imaging or
      postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%)
      extent by frozen and paraffin sections in the biopsied specimen showed positive
      ex vivo tumor images and positive antigen expression in resected gastric cancer
      specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33.
      In conclusion, humanized monoclonal antibody huA33 demonstrated selective
      localization to gastric cancer that expressed A33 antigen strongly. These
      excellent targeting characteristics of huA33 indicate potential for targeted
      therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and
      could also be exploitable for curatively resected early gastric cancer in an
      adjuvant setting.

PMID- 17034365
TI  - Ubiquitin-binding domains.
AB  - The covalent modification of proteins by ubiquitination is a major regulatory
      mechanism of protein degradation and quality control, endocytosis, vesicular
      trafficking, cell-cycle control, stress response, DNA repair, growth-factor
      signalling, transcription, gene silencing and other areas of biology. A class of
      specific ubiquitin-binding domains mediates most of the effects of protein
      ubiquitination. The known membership of this group has expanded rapidly and now
      includes at least sixteen domains: UBA, UIM, MIU, DUIM, CUE, GAT, NZF, A20 ZnF,
      UBP ZnF, UBZ, Ubc, UEV, UBM, GLUE, Jab1/MPN and PFU. The structures of many of
      the complexes with mono-ubiquitin have been determined, revealing interactions
      with multiple surfaces on ubiquitin. Inroads into understanding polyubiquitin
      specificity have been made for two UBA domains, whose structures have been
      characterized in complex with Lys48-linked di-ubiquitin. Several ubiquitin
      binding domains, including the UIM, CUE and A20 ZnF (zinc finger) domains,
      promote auto-ubiquitination, which regulates the activity of proteins that
      contain them. At least one of these domains, the A20 ZnF, acts as a ubiquitin
      ligase by recruiting a ubiquitin-ubiquitin-conjugating enzyme thiolester adduct
      in a process that depends on the ubiquitin-binding activity of the A20 ZnF. The
      affinities of the mono-ubiquitin-binding interactions of these domains span a
      wide range, but are most commonly weak, with Kd>100 microM. The weak interactions
      between individual domains and mono-ubiquitin are leveraged into physiologically
      relevant high-affinity interactions via several mechanisms: ubiquitin
      polymerization, modification multiplicity, oligomerization of ubiquitinated
      proteins and binding domain proteins, tandem-binding domains, binding domains
      with multiple ubiquitin-binding sites and co-operativity between ubiquitin
      binding and binding through other domains to phospholipids and small G-proteins.

PMID- 17034368
TI  - A new, simple method for quantifying gemcitabine triphosphate in cancer cells
      using isocratic high-performance liquid chromatography.
AB  - A deoxycytidine analog, gemcitabine (dFdC), is effective for treating solid
      tumors and hematological malignancies. After being transported into cancer cells,
      dFdC is phosphorylated to dFdC triphosphate (dFdCTP), which is subsequently
      incorporated into the DNA strand, thereby inhibiting DNA synthesis. Intracellular
      dFdCTP is the critical determinant for dFdC cytotoxicity, so therapeutic drug
      monitoring or in vitro testing of the capability of cancer cells to accumulate
      dFdCTP may be informative for optimizing dFdC administration. We have developed a
      new isocratic-elution high-performance liquid chromatography method for
      quantifying dFdCTP in cancer cells. Samples (500 microL) were eluted
      isocratically using 0.06 M Na(2)HPO(4) (pH 6.9) containing 20% acetonitrile, at a
      constant flow rate of 0.7 mL/min and at ambient temperature. Separation was
      carried out using an anion-exchange column (TSK gel DEAE-2SW; 250 mm x 4.6 mm
      inside diameter, particle size 5 microL) and monitored at 254 nm. The standard
      curve was linear with low within-day and interday variability. The lower
      detection limit (20 pmol) was as sensitive as that of the previous gradient
      elution method. dFdCTP was well separated from other nucleoside triphosphates.
      The method could measure dFdCTP in cultured or primary leukemic cells treated in
      vitro with dFdC. The method was also applicable to simultaneous determination of
      dFdCTP and cytarabine triphosphate, the results of which demonstrated ara-CTP
      production augmented by dFdC pretreatment. Thus, our isocratic high-performance
      liquid chromatography assay method will be of great use because of its
      sensitivity and simplicity as well as its applicability to biological materials.

PMID- 17034370
TI  - Retinoids and wound healing.
AB  - BACKGROUND: Retinoids are widely used in dermatology and may play a role in wound
      healing. The exact role of retinoids in wounds is confusing and controversial,
      however. Systemic retinoids are presumed to be detrimental to wound healing;
      however, this standard is based on isolated reports. OBJECTIVE: The objective was
      to provide a critical review of the available literature regarding the role of
      both topical and systemic retinoids in various aspects of wound healing.
      CONCLUSIONS: Pretreatment with retinoids likely promotes wound healing after
      facial resurfacing procedures and full- or partial-thickness wounds. While the
      evidence is mixed regarding the effects of retinoids applied to fresh and healing
      wounds, the majority of the evidence available shows favorable wound-healing
      properties in this setting. The medical-legal standard regarding the avoidance of
      facial resurfacing and surgical procedures in patients on or recently completing
      a course of systemic retinoids was likely prematurely established.

PMID- 17034371
TI  - Histometric and histochemical analysis of the effect of trichloroacetic acid
      concentration in the chemical reconstruction of skin scars method.
AB  - BACKGROUND: Atrophic scars can be induced by various causes, including severely
      inflamed acne, chicken pox, and trauma. Many treatment modalities are used for
      reconstructing and improving the appearance of scars with various treatment
      results. OBJECTIVE: A recent report shows the clinical efficacy of the chemical
      reconstruction of skin scars (CROSS) method, which consists of the focal
      application of trichloroacetic acid (TCA) in a higher concentration. Histometric
      analysis of the CROSS method, however, has not yet been established. METHODS: In
      this study, five hairless mice were used to evaluate the effect of the CROSS
      method and to analyze the difference between the CROSS method and simple TCA
      application. RESULTS: Similar histologic changes were observed in the two
      methods, including epidermal and dermal rejuvenation with new collagen
      deposition. These changes, however, were more prominent in the CROSS method
      treated areas, particularly when 100% TCA was used. CONCLUSION: The results of
      this study suggest that treatment of atrophic scars using the CROSS method is
      more effective than simple application of TCA in activating fibroblasts in the
      dermis and increasing the amount of collagen.

PMID- 17034373
TI  - Periorbital syringoma: a pilot study of the efficacy of low-voltage
      electrocoagulation.
AB  - BACKGROUND: Management of periorbital syringomas is problematic and avoided by
      many inexperienced physicians. The medical literature presently prefers CO(2)
      laser resurfacing to many other modalities, but the subject of electrosurgery has
      not been well explored. OBJECTIVES: To evaluate the clinical efficacy of
      electrocoagulation at low voltages in treating periorbital syringomas. MATERIALS
      AND METHODS: Twenty cases were collected during the period of 2002 through 2005.
      All cases were photographed before treatment with a dual-frequency 4-MHz
      radiofrequency device (Surgitron, Ellman International, Inc., Hewlett, NY) at a
      power of 1 to 2 in electrocoagulation mode. Six-week follow-up visits were
      scheduled to discuss occurrences and expectations, observe treatment effects, and
      apply further electrosurgery if needed. RESULTS: Clinical improvement increased
      with each subsequent treatment session. All patients scored either moderate or
      marked clinical improvement by their final visits, with 60% (11/18) revealing a
      marked clinical improvement (i.e., >70% clearance). The most common encountered
      adverse effects consisted of periorbital burning, swelling, redness, and
      pigmentary changes. CONCLUSION: Low-voltage electrocoagulation is an effective
      therapy for periorbital syringoma and should be considered when treating this
      difficult condition. To our knowledge, this is the first study utilizing
      electrocoagulation for removal of syringomas.

PMID- 17034372
TI  - Eflornithine cream combined with laser therapy in the management of unwanted
      facial hair growth in women: a randomized trial.
AB  - BACKGROUND: Eflornithine cream is approved for the reduction of unwanted facial
      hair in women. The mechanism of action for eflornithine is reduction in
      follicular cell growth rate, while laser photoepilation heats hair and adjacent
      tissues to suspend growth. OBJECTIVE: The objective was to assess the efficacy
      and safety of eflornithine or vehicle with laser therapy in the treatment of
      unwanted facial hair in women. METHODS: Subjects were randomized to treatment
      with eflornithine on one side of the face and vehicle on the contralateral side
      for 34 weeks. Subjects received Nd:YAG or alexandrite laser therapy to both sides
      of the face at Weeks 2 and 10. Blinded evaluations included left to right
      comparisons and appearance relative to baseline. RESULTS: Fifty-four women
      completed the trial. From Weeks 6 through 22, eflornithine-treated sides showed
      significant reduction in hair growth. By Week 34, no significant differences were
      seen. Subject grading showed significant and persistent hair reduction through
      Week 34 for eflornithine-treated sides. The safety profile for combination
      therapy is similar to eflornithine alone. CONCLUSION: Eflornithine is safely used
      in conjunction with laser hair removal treatments and promotes more rapid hair
      removal when combined with laser treatment. Patients demonstrate a clear
      preference for treatment with laser and eflornithine.

PMID- 17034374
TI  - Treatment of osmidrosis with the Cavitron ultrasonic surgical aspirator.
AB  - BACKGROUND: Axillary osmidrosis is an uncomfortable condition that can be a
      personal or social handicap. OBJECTIVE: The objective was to present the
      treatment of osmidrosis with the Cavitron ultrasonic surgical aspirator (CUSA).
      MATERIALS AND METHODS: Fifteen patients (3 males and 12 females) underwent
      surgery for bilateral axillary osmidrosis with the CUSA. RESULTS: The outcome of
      this operation with the CUSA was evaluated by the patients themselves according
      to the following criteria. Postoperative improvement was evaluated as good when
      the odor was decreased by >75%, fair when it was decreased by > or =50 and < or
      =75%, and poor when it was decreased by <50%. A total of 15 patients (3 males and
      12 females) were evaluated. Eight patients (53.3%) had a good result, 6 patients
      (40%) had a fairly good result, and 1 patient (6.7%) had a poor result. None of
      the patients experienced any complications, such as skin necrosis, infection, or
      serous cyst. One dissatisfied patient underwent reoperation and achieved a good
      result after the second procedure. CONCLUSIONS: This treatment of osmidrosis with
      the CUSA achieves satisfactory therapeutic efficacy.

PMID- 17034375
TI  - Reproducibility of two four-point clinical severity scores for lateral canthal
      lines (crow's feet).
AB  - BACKGROUND: Several clinical scoring systems have been used to evaluate the
      efficacy of botulinum toxin A in the treatment of hyperkinetic wrinkles. So far
      very few have been investigated for their reproducibility. OBJECTIVE: The aim of
      this study was to investigate the reproducibility of two clinical four-point
      scales for lateral canthal lines (crow's feet), at rest and at maximum smile.
      MATERIAL AND METHODS: Based on standardized photographs, a consensus atlas
      depicting the different severity grades [from 0 (none) to 3 (severe)] was
      developed. After training based on the atlas, 49 photographs at rest and 48 at
      maximum smile were graded by the same group of investigators on 2 consecutive
      days (n=9 on Day 1; n=8 on Day 2). The scores were compared for reproducibility
      using kappa statistics. RESULTS: Overall, reproducibility was good for both
      scales. Interobserver reproducibility showed an agreement of 0.6 at rest and 0.58
      at maximum smile (unweighted kappa). Intraobserver reproducibility showed an
      agreement between 0.47 and 0.86 at rest and between 0.62 and 0.81 at maximum
      smile (unweighted kappa). Using weighted kappa analysis, the agreement ranged
      between 0.63 and 0.91 at rest and between 0.71 and 0.85 at maximum smile.
      CONCLUSION: The clinical scales using scores of 0 to 3 for crow's feet, both at
      rest and at maximum smile, show a good inter- and intraobserver reproducibility.
      The use of these scores in clinical trials can be recommended.

PMID- 17034376
TI  - Actinic keratoses and the incidence of occult squamous cell carcinoma: a clinical
      histopathologic correlation.
AB  - BACKGROUND: The ability to clinically diagnose actinic keratoses (AKs) lesions
      has been taken for granted for some time. The importance of the malignant
      potential of these lesions is well known. However, a recent Phase IV, multicenter
      study assessing the long-term benefit of aminolevulinic acid-based photodynamic
      therapy provided a unique opportunity to prospectively examine the clinical
      histopathologic correlation of AKs. OBJECTIVE: The objective was to characterize
      the histopathology of clinically diagnosed AK lesions in the study population.
      METHODS: Punch biopsies of 220 clinically diagnosed untreated AKs were performed
      at baseline plus 51 lesions unresponsive to treatment (total, 271). RESULTS:
      Clinical diagnosis and histopathologic findings agreed in 91% (246/271) of the
      lesions biopsied. The balance of the biopsied lesions were: (1) benign changes 4%
      (11/271) and (2) occult cutaneous malignancy in 5% (14/271) of the cases, 12
      squamous cell carcinomas and 2 basal cell carcinomas. CONCLUSIONS: In this study,
      about 1 in 25 clinically diagnosed AK lesions identified by board-certified
      dermatologist investigator(s) were occult early-stage squamous cell carcinomas on
      histologic assessment, a fact surmised by the medical community that until now
      had not been well quantified. These findings should be considered when clinicians
      decide how to treat and manage AK patients.

PMID- 17034377
TI  - Treatment patterns and cost of nonmelanoma skin cancer management.
AB  - INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common form of cancer in
      the United States, more common than all other cancers combined. The factors that
      affect the cost of skin cancer management are not well defined. OBJECTIVE: The
      objective was to estimate cost of episodes of NMSC care and the factors that
      impact those costs. DESIGN: Medicare Current Beneficiary Survey (MCBS) data from
      1999 to 2000 were used to assess costs of episodes of NMSC care. MCBS estimates
      of the number of episodes occurring in three service settings (physician's
      office, outpatient/ambulatory surgical center, or hospital) and demographics were
      obtained. RESULTS: There were 497 episodes of care in 372 patients. Half the
      episodes were treated by dermatologists, and two-thirds were managed in
      physicians' offices. The mean episode cost for management in the office setting
      was 500 dollars (SD, +/- 487 dollars), and costs were higher when the episodes
      were treated in either the ambulatory surgical center or the hospital settings,
      935 dollars (SD, +/- 456 dollars) and 4,345 dollars (SD, +/- 4939 dollars),
      respectively. CONCLUSION: With the rising incidence and cost of NMSC to Medicare,
      it is increasingly important to preserve the low-cost management of this disease.
      Maintaining care of NMSC in the office-based setting is more cost-efficient than
      utilizing ambulatory surgical centers or hospital operating rooms.

PMID- 17034378
TI  - Use of intraoperative traction sutures in dermatologic surgery as an aid in
      visualization and stabilization in the operative field.

PMID- 17034379
TI  - Regression of atypical nevus: an anecdotal dermoscopic observation.
AB  - BACKGROUND: Clark nevi (atypical melanocytic nevi) can be considered as risk
      markers and potential precursors of melanoma. The authors report on the
      morphologic changes of an atypical nevus by dermoscopic follow-up examination
      over a 7-year period. CASE REPORT: A 43-year-old man had a brown macule on his
      back, sized 5 mm, with an irregular shape, clinically and dermoscopically
      diagnosed as an equivocal melanocytic lesion. Dermoscopically during the initial
      examination, a predominant reticular pattern with peripheral eccentric
      hyperpigmentation in the lower portion of the lesion could be seen. After 7
      months, the area of peripheral eccentric hyperpigmentation had regressed, and
      after 4.5 years the atypical pigment network had almost disappeared. After 7
      years of follow-up, a diffuse area of hypopigmentation and a residual light brown
      pigmentation were detectable. The histopathologic diagnosis was consistent with
      an atypical junctional nevus with regression with features of a Clark nevus.
      CONCLUSION: Based on our observation, even a dermoscopically atypical nevus may
      undergo regression as documented by long-term dermoscopic follow-up.

PMID- 17034380
TI  - Bilateral hatchet flaps.

PMID- 17034381
TI  - Aggressive extraocular sebaceous carcinoma in a 52-year-old man.

PMID- 17034382
TI  - Ultralate metastasis of cutaneous melanoma.

PMID- 17034383
TI  - Sebaceous carcinoma on the scalp.

PMID- 17034385
TI  - Who is still using lip implants?

PMID- 17034384
TI  - Mohs micrographic surgery, sentinel lymph node mapping, and estrogen receptor
      analysis for the treatment of malignant nodular hidradenoma.

PMID- 17034386
TI  - The effect of epidermal graft on a suction blistered donor wound.

PMID- 17034387
TI  - Protective positioning of the surgeon's fingers.

PMID- 17034389
TI  - Psychological assessment of the headache patient.
AB  - Most clinicians agree that psychological factors are important considerations in
      the evaluation and treatment of headache patients. There has been a lack of
      systematic research, however, that has examined the relationship between these
      variables. Attention to such factors may become a greater concern as the
      frequency of a patient's headaches increases, there is increased disability
      secondary to headaches, and/or there is an inadequate response to usually
      effective treatment. In addition, there is no consensus as to the proper method
      to assess psychopathology in headache patients.

PMID- 17034390
TI  - Basic principles and techniques of cognitive-behavioral therapies for comorbid
      psychiatric symptoms among headache patients.
AB  - Recent research on headache has focused on identifying the prevalence of
      psychiatric disorders in headache patients and discerning the impact of
      psychiatric comorbidity on treatment of headache. The presence of comorbid
      psychiatric disorders, especially anxiety and depression, in headache patients is
      now a well-documented phenomenon. Existing but limited empirical data suggest
      that psychiatric comorbidity exacerbates headache and negatively impacts
      treatment of headache. Problematically, these findings have not yet eventuated in
      improved treatments for individuals suffering from both headache and a
      psychiatric disorder(s). The present article is an attempt to describe the
      application of cognitive-behavioral therapies (CBT) for depressive and anxiety
      disorders to headache patients who present with psychiatric comorbidity. We
      discuss the origins of the chronic care model in relation to CBT, review basic
      cognitive-behavioral principles in treating depression and anxiety, and offer
      clinical recommendations for integrating CBT into existing headache treatment
      protocols. Directions for future research are outlined, including the need for
      treatment outcome studies that examine the effects of treating comorbid
      psychiatric disorders on headache (and vice versa) and the feasibility of
      developing an integrated CBT protocol that addresses both conditions
      simultaneously.

PMID- 17034391
TI  - Pharmacological management of mood and anxiety disorders in headache patients.
AB  - There is emerging evidence that treatment of comorbid mood and anxiety disorders
      can improve headache treatment outcome when implemented within a comprehensive
      program. Effective treatment for comorbid mood and anxiety disorders requires
      screening headache patients and accurately diagnosing specific psychiatric
      disorders when present. Specific dual-action antidepressant, anticonvulsant, and
      atypical antipsychotic medications can serve as dual agents that simultaneously
      treat both headaches and a mood or anxiety disorder. Serotonin reuptake
      inhibitors and most other antidepressant, anxiolytic, and mood-stabilizing
      medications are generally ineffective for headache prophylaxis. However, they can
      be safely added to a headache regimen for treatment of a comorbid psychiatric
      disorder. Treatment of comorbid psychiatric disorders in headache patients
      requires patient education about the psychiatric disorder, its treatment,
      possible side-effects, and expected benefits. Clinicians need to be sensitive to
      possible stigma that some patients fear from a psychiatric diagnosis or its
      treatment.

PMID- 17034392
TI  - Behavioral facilitation of medical treatment of headache: implications of
      noncompliance and strategies for improving adherence.
AB  - Clinical recommendations were gleaned from a review of treatment adherence
      published in the regular issue of Headache (released in tandem with this
      supplement). The recommendations include: (1) Nonadherence is prevalent among
      headache patients, undermines treatment efficacy, and should be considered as a
      treatment variable; (2) Calling patients to remind them of appointments and
      recalling those who miss a scheduled appointment are fundamentally the most cost
      effective adherence-enhancing strategies, insofar as failed appointment-keeping
      acts as a ceiling on all future treatment and adherence efforts; (3) Simplified
      and tailored medication regimens improve adherence (eg, minimized number of
      medications and dosings, fixed-dose combinations, cue-dose training, stimulus
      control); (4) Screening and management of psychiatric comorbidities, especially
      depression and anxiety, is encouraged; (5) The concept of self-efficacy as a
      modifiable psychological process often can be employed to predict and improve
      adherence.

PMID- 17034393
TI  - Modifiable risk factors for migraine progression (or for chronic daily headaches)
      -clinical lessons.
AB  - Herein we summarize clinical issues gleaned from a full peer-reviewed article on
      modifiable risk factors for migraine. Since migraine is progressive in some but
      not in most individuals, identifying patients at risk for progression is crucial.
      Key interventions include: (1) Decrease headache frequency with behavioral and
      pharmacologic interventions; (2) Monitor the body mass index and encourage
      maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine
      overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and
      treat depression and other psychiatric comorbidities. These recommendations have
      not been demonstrated to improve outcomes in longitudinal studies.

PMID- 17034394
TI  - Sleep and headache disorders: clinical recommendations for headache management.
AB  - Clinical practice points were drawn from a review of sleep and headache disorders
      published in the regular issue of Headache (released in tandem with this
      supplement). The recommendations include: (1) Sleep as well as psychiatric
      disorders tend to become prevalent in more complex and severe headache patterns
      and regulation of sleep and mood may favorably impact headache threshold; (2)
      Specific headache patterns, irrespective of headache diagnosis, are suggestive of
      a potential sleep disorder (eg, "awakening" or morning headache, chronic daily
      headache); (3) Sleep disorders most implicated with headache include obstructive
      sleep apnea, primary insomnia, and circadian phase abnormalities, and treatment
      of such sleep disorders may improve or resolve headache; (4) Inexpensive
      screening tools (eg, sleep history interview, headache/sleep diary, validated
      questionnaires, prediction equations) aid identification of patients warranting
      polysomnography; and (5) Pharmacologic and behavioral therapies are effective in
      the regulation of sleep and are compatible with usual headache care.

PMID- 17034395
TI  - Suggestions for a biopsychosocial approach to treating children and adolescents
      who present with headache.
AB  - An evidence-based, biopsychosocial approach to the care of pediatric patients who
      present with the complaint of headache is recommended. This approach informs
      diagnosis and management decisions, is critical for maximizing adherence to the
      prescribed headache treatment regimen, and incorporates assessment of the impact
      of headache on a child/adolescent's quality of life, disability, and emotional
      functioning. Very often, successful treatment of headache leads to improvements
      in disability and emotional functioning. When this is not the case, or when the
      work-up shows that comorbid headache and psychiatric disorders are present for a
      patient, a more comprehensive treatment approach that includes the active
      collaboration of pediatric specialists in headache care and mental health care is
      warranted.

PMID- 17034396
TI  - "Are you talking to me?" confronting behavioral disturbances in patients with
      headache.
AB  - The famous question, "Are you talking to me?," was coined by Robert DeNiro in his
      lead role as Travis Bickle in the Martin Scorsese classic, Taxi Driver. The
      phrase also characterizes the troubling encounters that many headache-treating
      professionals confront as they attempt to discuss serious matters of care and
      compliance with some of their headache patients. Although most headache patients
      are eager to take professional advice and guidance, there exists a minority of
      patients whose behavior undermines a collaborative relationship between doctor
      and patient. In these cases, the physician may need to directly confront this
      behavior in order to overcome behavioral barriers that interfere with desirable
      treatment outcomes. This article offers explicit means and strategies to engage
      difficult patients, increase the likelihood of program adherence and improvement,
      and develop a more satisfying doctor-patient relationship, based on clinical
      experience in a national referral center for difficult-to-manage headache
      patients.

PMID- 17034397
TI  - Understanding the patient with complex psychiatric comorbidities: a
      psychologist's perspective.

PMID- 17034398
TI  - Understanding the headache patient with complex comorbidities: a primary care
      physician's perspective.

PMID- 17034399
TI  - Understanding the headache patient with complex psychiatric comorbidities: a
      neurologist's perspective.

PMID- 17034400
TI  - Understanding the headache patient with complex psychiatric comorbidities: a
      headache specialist's perspective.

PMID- 17034401
TI  - Psychiatric comorbidity with chronic headache: evidence-based clinical
      implications--introduction to the supplement.

PMID- 17034402
TI  - Mood and anxiety disorders in chronic headache.
AB  - Although most individuals with recurrent headache disorders in the general
      population do not experience severe psychopathology, population-based studies and
      clinical investigations find high rates of comorbidity between headache and mood
      and anxiety disorders. When present, psychiatric disorders may complicate
      headache treatment and portend a poorer treatment response. The negative
      prognosis associated with psychiatric comorbidity emphasizes the importance of
      the identification of psychopathology among those with headache beginning at an
      early age, and suggests that the treatment of psychiatric comorbidity is
      warranted to improve the outcome of headache management. In this article we
      describe the mood and anxiety disorders most commonly associated with migraine,
      tension-type headache, and chronic daily headache. We provide recommendations for
      the assessment of comorbid mood and anxiety disorders as well as a brief overview
      of treatment options. Last, we discuss the clinical implications of mood and
      anxiety disorders on the treatment and outcome of headache.

PMID- 17034403
TI  - Medication overuse headache: biobehavioral issues and solutions.
AB  - This article reviews current research on medication-overuse headache (MOH), and
      provides clinical suggestions for effective treatment programs. Epidemiological
      research has identified reliance on analgesics as a predictive factor in headache
      chronicity. MOH can be distinguished as simple (Type I) or complex (Type II).
      Simple cases involve relatively short-term drug overuse, relatively modest
      amounts of overused medications, minimal psychiatric contribution, and no history
      of relapse after drug withdrawal. In contrast, complex cases often present with
      multiple psychiatric comorbidities and a history of relapse. Although limited,
      current research suggests that comorbid psychiatric disorders are more prevalent
      in MOH than in control headache conditions, and may precede the onset of MOH.
      There appears to be an elevated risk of family history of substance use disorders
      in MOH patients, and an increased risk of MOH in patients with diagnosed
      personality disorders. Current studies suggest a high rate of relapse at 3 to 4
      years after drug withdrawal and pharmacological treatment, with most relapse
      occurring during the first year of treatment. Relapse is a greater problem with
      analgesics than ergots or triptans. The addition of behavioral treatment to
      prophylactic medication may significantly reduce the risk of relapse over a
      period of several years. Clinical recommendations include assessment and
      modification of psychological factors that may underlie MOH, provision of
      detailed educational information, and combining behavioral treatment with the
      current standard of drug withdrawal and use of prophylactic pharmacotherapy.

PMID- 17034404
TI  - A review of screening tools for psychiatric comorbidity in headache patients.
AB  - Psychiatric comorbidity, especially depression and anxiety, has been well
      documented in patients with primary headache disorders. The presence of
      psychiatric comorbidity in headache patients is associated with decreased quality
      of-life, poorer prognosis, chronification of disease, poorer response to
      treatment, and increased medical costs. Despite the prevalence and impact,
      screening for psychiatric disorders in headache patients is not systematically
      performed, either clinically or in research studies, and there are no guidelines
      to suggest which patients should be screened or in what manner. We review a
      variety of screening methods and instruments, focusing primarily on self-report
      measures and those available in the public domain. Informal verbal screening may
      be sufficient in a primary care setting, but should include screening for both
      anxiety and depression. Explicit screening for anxiety is important, as anxiety
      may have a more significant impact on headache than does depression and may occur
      in the absence of clinical depression. Formal screening with instruments that can
      identify a variety of psychiatric disorders is appropriate for patients with
      daily headache syndromes, patients who are refractory to usual care, and patients
      referred for specialty evaluation. Limitations of screening instruments include
      the influence of transdiagnostic symptoms and the need for confirmatory
      diagnostic interview. The following instruments appear most suitable for use in
      headache patients: for depression, the Patient Health Questionnaire Depression
      Module, the Beck Depression Inventory-II, or the Beck Depression Inventory
      Primary Care; for anxiety, the Beck Anxiety Inventory and the Generalized Anxiety
      Disorder 7-item Scale; and for multidimensional psychiatric screening, the
      Patient Health Questionnaire or Primary Care Evaluation of Mental Disorders.

PMID- 17034405
TI  - The role of intrinsic and induced vulnerability in electrically induced cardiac
      arrhythmias.

PMID- 17034406
TI  - A beat is born: embryonic development of arrhythmogenesis.

PMID- 17034407
TI  - Clustering of ventricular arrhythmias: a therapeutic opportunity or strictly a
      marker of poor prognosis?

PMID- 17034408
TI  - Dual-chamber pacemakers as long-term telemetry devices: ready for prime-time in
      diagnosing unsuspected atrial fibrillation?

PMID- 17034409
TI  - Sexual function in women with urinary incontinence treated by pelvic floor
      transvaginal electrical stimulation.
AB  - INTRODUCTION: Women's sexual dysfunctions (WSD) have been commonly associated
      with urinary incontinence (UI). Women with UI and who scored low on the Female
      Sexual Function Index (FSFI) showed an improvement in urinary leakage and also in
      their sexual life following treatment by transvaginal electrical stimulation
      (TES). AIMS: To determine the effects of TES in 37 women complaining of UI, of
      whom 23 also had WSD, and to compare the FSFI scores of women with UI and 43
      women not affected by UI who underwent routine urologic evaluation. METHODS:
      Thirty-seven women complaining of UI were evaluated by voiding diary and with
      FSFI before and after 3 months of TES. All had a urogynecologic evaluation and
      urodynamic study. MAIN OUTCOME MEASURES: In the voiding diary the women reported
      the types of liquid they ingested, urinary frequency, and episodes of urgency and
      urine leakage. The domain scores of the FSFI, including desire, arousal,
      lubrication, orgasm, satisfaction, and pain, were calculated. TES was conducted
      for 15-30 minutes, twice a week for 3 months, using biphasic intermittent current
      with a frequency of 50 Hz for stress UI (SUI) and 20 Hz for urge UI (UUI), and
      the most tolerable intensity of stimulation. RESULTS: After TES, only two of the
      10 women with UUI experienced a few leakage incidents; patients with SUI were
      completely dry during TES; and only three reported a few episodes of UI during
      intense activities. The five patients with mixed UI improved mainly as regards
      urgency. The FSFI scores of patients complaining of UI showed significantly lower
      desire and sexual satisfaction, and higher sexual pain than controls. After 3
      months, the 23 women affected by WSD, of the 37 participants with UI, reported a
      remarkable improvement in their sexual life. CONCLUSIONS: TES was found to be a
      safe and effective therapy for selected patients affected by mild to moderate UI.
      Because women with UI also complain of WSD compared with the general female
      population, an investigation of female sexuality is suggested for these patients.

PMID- 17034410
TI  - Nonpalpable scarring of the penile septum as a cause of erectile dysfunction: an
      atypical form of Peyronie's disease.
AB  - INTRODUCTION: Men with nonpalpable isolated septal scars (ISS) identified with
      color duplex ultrasonography (CDU) comprise a group of previously unrecognized
      patients with wide-ranging sexual concerns. AIM: We aim to identify the clinical
      characteristics of patients presenting with this atypical form of Peyronie's
      disease characterized by the absence of palpable deformity. MATERIALS AND
      METHODS: Of 482 consecutive patients who presented to a tertiary care erectile
      dysfunction (ED) clinic and underwent CDU after satisfying inclusion criteria, 27
      (5.6%) men with nonpalpable ISS and no dorsal or ventral plaque were identified.
      MAIN OUTCOME MEASURES: International Index of Erectile Function (IIEF), CDU, and
      clinical characteristics. RESULTS: The median age of the men with nonpalpable ISS
      was 49 years. The length of time from onset of symptoms to presentation was 22
      months, and the pretreatment IIEF score was 14. The remaining 455 men who
      underwent CDU were of similar age (48 years) but had a markedly lower IIEF score
      of 9.5 (statistical median). ISS patients presented with decreased penile
      rigidity (20), penile shortening (13), chronic pain with erection (13; mean 33
      months), and the inability to maintain an erection (7). Fourteen men had failed
      phosphodiesterase-5 inhibitor therapy, and four reported unsatisfactory results.
      Management options included retrial with oral agents, intracavernous
      pharmacotherapy, verapamil injections, and surgery. CONCLUSIONS: The clinician
      should be suspicious for nonpalpable ISS in men with sexual concerns who present
      with decreased penile rigidity, length loss, and chronic pain with erection. Our
      findings support the use of CDU for this patient group, particularly when
      previous treatment has failed, because men with ISS had a greater likelihood of
      having no palpable deformity or curvature and ongoing penile pain.

PMID- 17034411
TI  - Evaluating the impact of overactive bladder on sexual health in women: what is
      relevant?
AB  - INTRODUCTION: To assess sexual health, relevant, valid, and reliable
      questionnaires need to be used. AIM: To assess the relevance and content validity
      of three sexual health questionnaires in women with overactive bladder (OAB) and
      urinary incontinence. MAIN OUTCOME MEASURES: Sexual Quality of Life Questionnaire
      -Female (SQoL-F), Sexual Function Questionnaire (SFQ), and Pelvic Organ Prolapse
      Incontinence Sexual Function Questionnaire (PISQ). METHODS: Women with OAB and
      urinary incontinence were recruited from five urology clinics in the United
      States; those who were interested in participating were mailed questionnaire
      packets with instructions. Each questionnaire item was followed by three
      questions regarding the understandability, relevance, and impact of bladder
      condition when responding to the question. Patients returned the completed
      questionnaires by mail; clinical information was obtained from chart review.
      RESULTS: A total of 129 patients (74% response) returned the questionnaires. The
      mean age was 56 years; 78% were white; 64% were married. In this sample, 64% had
      urge incontinence; 32% had mixed incontinence; and 4% had stress incontinence.
      Participants experienced bladder symptoms for a mean of 12.2 years with the
      following treatments: surgery (43%), bladder training (26%), exercise/biofeedback
      (42%), and medications (67%). SQoL-F items were understood by more than 97% of
      the respondents, more than 89% for SFQ, and more than 82% for PISQ. There were
      two SQoL-F items, one SFQ item, and 11 PISQ items that less than 60% of the
      respondents deemed relevant to their bladder condition. Correlations among
      questionnaire items and relevance to bladder condition ranged from 0.04 to 0.64
      for the SQoL-F, 0.04 to 0.47 for the SFQ, and 0.01 to 0.58 for the PISQ.
      CONCLUSION: Women with OAB found the majority of items on all three
      questionnaires to be relevant to their bladder condition. Of these
      questionnaires, the SQoL-F had the highest understandability, fewest questions
      considered irrelevant, and correlated well with OAB symptoms.

PMID- 17034412
TI  - Comparison of colonization dynamics and pathology of mice infected with
      enteropathogenic Escherichia coli, enterohaemorrhagic E. coli and Citrobacter
      rodentium.
AB  - Enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and
      Citrobacter rodentium (CR) colonize the gastrointestinal tract epithelium via
      attaching and effacing lesions. While humans are believed to be the only living
      reservoir of typical EPEC and EHEC to have border host specificity, CR is a
      restricted mouse pathogen. Recently, conflicting conclusions were reported
      concerning the utility of a murine model to study mechanisms of EPEC and EHEC
      colonization and infection. We therefore aimed to compare colonization dynamics
      of EPEC, EHEC and CR, together with a commensal E. coli (Nissle) as a control, in
      the murine. We show that all strains are equally shed in stools over the first 48
      h post inoculation. However, while the CR population then rapidly expanded the
      EPEC, EHEC and Nissle populations quickly declined to a level just above
      detection. We conclude that following oral inoculation EPEC and EHEC develop a
      commensal, rather than pathogenic, interaction within the mouse host.

PMID- 17034413
TI  - Identification and characterization of ENA ATPases HwENA1 and HwENA2 from the
      halophilic black yeast Hortaea werneckii.
AB  - Two genes, HwENA1 and HwENA2, which encode ENA-like ATPases in the extremely
      halotolerant black yeast Hortaea werneckii, were cloned and sequenced. Although
      the expression of both genes is responsive to salt, the transcription of the
      HwENA1 gene was induced at a higher level when the cells were exposed to salt
      stress, and the expression of HwENA2 gene was higher in the adapted cells,
      suggesting their different roles in maintaining alkali cation homeostasis.
      According to the phylogenetic tree based on the amino acid sequences, they
      represent a new group of fungal P-type ATPases. The comparison of both amino acid
      sequences with other fungal ENA ATPases, together with salt- and pH-responsive
      gene expression, suggests that newly identified ENA genes could be involved in
      maintaining low Na(+)/K(+) content in H. werneckii.

PMID- 17034415
TI  - Differential effect of auxotrophies on the release of macromolecules by
      Salmonella enterica vaccine strains.
AB  - Attenuated Salmonella enterica strains have been widely used as live carriers for
      vaccines and therapeutic molecules. Appropriate attenuation has been introduced
      into such bacteria for safety reasons and the improvement of strain properties.
      Here, we compared two strains that were rendered auxotroph for diaminopimelic
      acid or thymidine monophosphate precursors by deletion of the genes asd or thyA,
      respectively. Upon removal of the complementing compound from bacterial cultures,
      both strains quickly lose their property to form colonies. However, while the
      Deltaasd bacteria lysed almost immediately under such conditions, DeltathyA
      bacteria remained physically intact during the observation period. As a
      consequence, the Deltaasd bacteria released their intracellular content such as
      proteins or plasmids into the supernatant. In contrast, no intracellular
      component, either proteins or plasmids, could be recovered from the supernatants
      of DeltathyA bacteria upon depletion of thymidine. Thus, the release of
      macromolecules from the bacterial carrier occurs as a consequence of appropriate
      lethal attenuation. This might substitute for sophisticated secretion systems.

PMID- 17034414
TI  - Phenotypic characteristics, virulence profile and genetic relatedness of O157
      Shiga toxin-producing Escherichia coli isolated in Brazil and other Latin
      American countries.
AB  - Thirty-eight Shiga toxin-producing Escherichia coli (STEC) O157:H7/H(-) strains
      isolated from human infections, cattle and foods in Brazil and in some other
      Latin American countries were compared with regard to several phenotypic and
      genotypic characteristics. The genetic relatedness of the strains was also
      determined by pulsed-field gel electrophoresis (PFGE). Similar biochemical
      behaviour was identified, regardless of the origin and country of the strains.
      Most (89.5%) strains were sensitive to the antimicrobial agents tested, but
      resistance to at least one drug was observed among bovine strains. Although a
      diversity of stx genotypes was identified, most (77.8%) of the human strains
      harboured stx(2) or stx(2)stx(2c(2vha)), whereas stx(2c(2vha)) prevailed (64.2%)
      among strains isolated from cattle. stx(1) and stx(1)stx(2c(2vha)) were the
      genotypes identified less frequently, and occurred exclusively among strains
      isolated from food and cattle, respectively. Despite differences in the stx
      genotypes, all strains carried eae-gamma, efa1, ehx, iha, lpf(O157) and toxB
      sequences. Many closely related subgroups (more than 80% of similarity) were
      identified by PFGE, and the presence of a particular O157:H7 STEC clone more
      related to human infections in Brazil, as well as a common origin for some
      strains isolated from different sources and countries in Latin America can be
      suggested.

PMID- 17034416
TI  - Aryloxoalcanoic compounds induce resistance to antibiotic therapy in urinary
      tract infection caused by Escherichia coli.
AB  - Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and
      ethacrynic acid (ET) is administered to enhance diuresis. These compounds are
      structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D),
      as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by
      the renal route, they could potentially coexist with Escherichia coli in the
      urinary tract of infected patients. Induction of the in vitro resistance of E.
      coli to hydrophilic antibiotics was determined by increasing the values of the
      minimum inhibitory concentration (2-40-fold). These results correlated with
      drastically inhibited expression of the hydrophilic bacterial channel OmpF. In
      vivo assays were performed in ascending urinary tract infection in female BALB/c
      mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg(-1) day(-1)
      by the oral route diminished renal infection. The CFU mean values in the kidneys
      were between 75% and 89% lower than those in animals without treatment.
      Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg(-1) day(-1)) did
      not change the effect of the treatment. In contrast, ET at 2.9 mg kg(-1) day(-1)
      or 2,4-D at 70 mg kg(-1) day(-1) inhibited the antibiotic therapeutic effect.
      Moreover, 2,4-D dramatically increased bacterial infection after 9 days of
      exposure.

PMID- 17034417
TI  - Whey-derived free fatty acids suppress the germination of Candida albicans in
      vitro.
AB  - Bovine whey from the cheese-making industry contains several bioactive factors
      that promote health and prevent disease. Although many efforts have been made
      over the years to show that immunoglobulins, lactoperoxidase, lactoferrin,
      lysosyme and small peptides present in whey have antimicrobial activities against
      several pathogenic microorganisms, such activities have not been investigated so
      far for the lipid fraction of whey. Here, we have used an in vitro assay-based
      fractionation procedure to show that free fatty acids derived from whey cream
      specifically inhibit the germination of Candida albicans, a morphologic change
      associated with pathogenicity. Further fractionation by HPLC demonstrated that
      this activity can be mainly attributed to lauric acid, myristoleic acid, linoleic
      acid and arachidonic acid.

PMID- 17034418
TI  - Effect of treatment with a colloidal oatmeal lotion on the acneform eruption
      induced by epidermal growth factor receptor and multiple tyrosine-kinase
      inhibitors.
AB  - Current treatment modalities for epidermal growth factor (EGFR)-positive cancers
      have recently included the use of antibodies and small-molecule tyrosine-kinase
      inhibitors (TKI). A significant limiting step in the use of these agents is
      dermatological toxicity, frequently in the form of an acneiform eruption. Present
      management modalities for this toxicity are largely ineffective. Colloidal
      oatmeal lotion demonstrates multiple anti-inflammatory properties with known
      effects on arachidonic acid, cytosolic phospholipase A2 and tumour necrosis
      factor-alpha pathways, along with an excellent side-effect profile. Treatment
      with colloidal oatmeal was applied to 11 patients with a rash induced by
      cetuximab, erlotinib, panitumumab and sorafenib. Of the 10 assessable patients, 6
      had complete response and 4 partial response, giving a response rate of 100% with
      no associated toxicities. Treatment with colloidal oatmeal lotion is efficient in
      controlling the rash associated with EGFR and multiple TKI, and allows
      continuation of the antineoplastic treatment.

PMID- 17034419
TI  - Erythema elevatum diutinum manifesting as a penile ulcer.

PMID- 17034420
TI  - Solar urticaria as a manifestation of Churg-Strauss syndrome.

PMID- 17034421
TI  - Anomalies in dermal ridge arrangement in Down's syndrome.

PMID- 17034422
TI  - Thorium X and skin cancer: still a problem in the 21st century.

PMID- 17034423
TI  - Peripheral neuropathy associated with nodular prurigo.
AB  - Nodular prurigo is characterized by nodules and papules that are intensely
      pruritic. Thalidomide is used to treat patients with recalcitrant disease.
      Because thalidomide may cause peripheral neuropathy, it is current practice to
      perform nerve conduction studies to exclude subclinical neuropathy before
      treatment. The clinical record of eight patients with nodular prurigo, in whom
      thalidomide treatment was proposed, were looked at. Five of them showed evidence
      of subclinical neuropathy, thereby contraindicating the use of thalidomide. None
      of the patients had any symptoms of a peripheral neuropathy and none was taking
      any medications with a recognized potential to cause peripheral neuropathy. We
      propose that nodular prurigo may be associated with an underlying peripheral
      neuropathy in a subset of patients. In patients with nodular prurigo and
      demonstrable peripheral neuropathy, there may be a role for treatment with agents
      such as amitryptiline and gabapentin, which are normally used for neuropathic
      pain.

PMID- 17034424
TI  - Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but
      enhancement of MyD88-independent interferon-beta production.
AB  - Toll-like receptors (TLRs) signal through two main pathways: a myeloid
      differentiation factor (MyD)88-dependent pathway that acts via nuclear factor
      kappaB (NF-kappaB) to induce proinflammatory cytokines such as tumour necrosis
      factor-alpha (TNF-alpha) and a MyD88-independent pathway that acts via type I
      interferons to increase the expression of interferon-inducible genes. Repeated
      signalling through TLR4 and a number of other TLRs has been reported to result in
      a reduction in the subsequent proinflammatory cytokine response, a phenomenon
      known as TLR tolerance. In this study we have shown that, whilst NF-kappaB
      activation and production of TNF-alpha and interleukin-12 by murine RAW264.7 and
      J774.2 cells in response to stimulation by TLR4, -5, -7 or -9, was reduced by
      prior stimulation with TLR4, -5, -7 or -9 ligands, the primary stimulation of
      TLR3, which does not use the MyD88 pathway, did not reduce the TNF-alpha or
      interleukin-12 responses to subsequent TLR stimulation. The response to TLR3
      stimulation was not diminished by prior TLR ligand exposure. Furthermore, the
      production of interferon-beta (IFN-beta) following stimulation of TLR3 or -4,
      which is MyD88-independent, was increased by prior activation of TLR4, -5, -7 or 
      9. In contrast, TLR9 ligand-induced IFN-beta production, which is MyD88
      dependent, was tolerized by prior TLR stimulation. These results are consistent
      with differential regulation of MyD88-dependent and MyD88-independent cytokine
      production following serial activation of TLRs.

PMID- 17034426
TI  - Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40
      stimulation.
AB  - It has recently been shown that immature dendritic cells (DCs) stimulated by a
      danger signal undergo transient maturation followed by exhaustion. However, the
      exact mechanism for this has not been elucidated. In this study, we show that
      interleukin-10 (IL-10) secreted from transiently matured DCs stimulated by danger
      signals is responsible for this rapid DC exhaustion. Blocking of the autocrine IL
      10 enabled transient mature DCs to maintain the mature phenotype for several
      days. However, these DCs remained phenotypically unstable because the addition of
      IL-10 altered the transient mature DCs to exhausted DCs. More importantly,
      stimulation of DCs by CD40 protected transient mature DCs from IL-10-dependent
      exhaustion, with the result that mature DCs remained stable in the presence of IL
      10. Furthermore, in vivo administration of stable mature DCs pulsed with
      ovalbumin protein induced antigen-specific cytotoxic T lymphocytes (CTLs)
      effectively, whereas neither exhausted DCs nor transient mature DCs were able to
      prime a strong antigen-specific CTL response. These results indicate that DC-T
      cell engagement via CD40-CD154 is required for stable DC maturation leading to
      effective CTL induction. Otherwise, DCs stimulated solely by a danger signal are
      temporarily activated, but then rapidly lose their immune-activating capacity
      under the influence of autocrine IL-10.

PMID- 17034425
TI  - Workshop cluster 1+ gammadelta T-cell receptor T cells from calves express high
      levels of interferon-gamma in response to stimulation with interleukin-12 and 
      18.
AB  - Gammadelta T-cell receptor(+) T lymphocytes are an important element of the
      innate immune system. Early production of interferon (IFN)-gamma by gammadelta T
      cells may have a role in linking innate and adaptive immune responses and
      contribute to T helper-1 bias. We investigated the role of cytokines in the
      activation and induction of IFN-gamma secretion by bovine workshop cluster 1(+)
      (WC1(+)) gammadelta T cells. The effects of culture with interleukin (IL)-12, IL
      18, IL-15 and IL-2 were investigated; these cytokines are known to influence
      murine and human gammadelta T cells. We report that bovine WC1(+)gammadelta T
      cells are synergistically stimulated by IL-12 and IL-18 to secrete large
      quantities of IFN-gamma. Neonatal calves were shown to have significantly higher
      numbers of circulating WC1(+)gammadelta T cells than adult animals. In addition,
      the response of peripheral blood WC1(+)gammadelta T cells was significantly
      higher in neonatal calves compared with adult animals. However, in adult animals
      the response of lymph node WC1(+)gammadelta T cells to IL-12/IL-18 was more
      pronounced than that of peripheral blood WC1(+)gammadelta T cells. We hypothesize
      that the induction of IFN-gamma secretion from WC1(+)gammadelta T cells by IL-12
      and IL-18 is likely to be an important element of the innate response to
      pathogens such as Mycobacterium bovis. The high numbers of WC1(+)gammadelta T
      cells in neonatal calves, and their inherent ability to respond to inflammatory
      cytokines, could be a key factor in the enhanced responses seen in calves to BCG
      vaccination.

PMID- 17034428
TI  - Avoiding potential misuses of addiction brain science.

PMID- 17034427
TI  - Major histocompatibility complex class II (DR) antigen and costimulatory
      molecules on in vitro and in vivo activated human polymorphonuclear neutrophils.
AB  - We have previously shown that normal human peripheral blood polymorphonuclear
      neutrophils (PMNs) contain cytoplasmic 'stores' of three key molecules normally
      associated with antigen presentation and T-cell costimulation, i.e. major
      histocompatibility complex class II (DR) antigen, CD80 (B7-1) and CD86 (B7-2).
      These cytoplasmic molecules were found to translocate to the cell surface within
      a few minutes following cross-linking (X-L) of Mac-1: an early neutrophil
      activation signal. In this study we have compared X-L of Mac -1 in parallel with
      four other well documented in vitro neutrophil activators: phorbol myristate
      acetate, N-formyl methionyl leucyl phenylalanine, lipopolysaccharide, and
      phagocytosis of immunoglobulin G-Latex particles. In addition, we have used
      paired samples of neutrophils obtained from peripheral blood (as a control) and
      synovial fluid from patients with rheumatoid arthritis as a source of in vivo
      activated cells. With the exception of phagocytosis, all activators resulted in
      the rapid (within 30 min) generation of two populations of activated neutrophils
      (designated P1 and P2) based on flow-cytometry measurements of size, granularity
      and phenotype. Significant up-regulation of DR and costimulatory molecules was
      observed, predominantly on P2 cells, with all activators except phagocytosis.
      CD80 and CD86 were noted to respond to the various activation signals in a
      different pattern suggesting that their intracellular granule location may be
      different. Dual-staining confocal laser microscopy studies showed that CD80 is
      largely confined to secretory vesicles (SVs) while CD86 appears to have a much
      wider distribution being found in SVs and within secondary (specific) and primary
      (azurophilic) granules. Increased surface expression of these antigens was also
      observed on P2 synovial fluid neutrophils appearing as large heterogeneous
      clusters on the cell surface when visualized by confocal laser microscopy.

PMID- 17034429
TI  - Digitizing and democratizing historical research.

PMID- 17034430
TI  - Contingency management and the addictions.

PMID- 17034431
TI  - Hypothalamic-pituitary-adrenal axis and substance use: so many questions--and we
      can answer them.

PMID- 17034432
TI  - Matching clients' treatment goals with treatment oriented towards abstinence,
      moderation or harm reduction.

PMID- 17034433
TI  - Sweden--is alcohol becoming an ordinary commodity?

PMID- 17034434
TI  - Contingency management for treatment of substance use disorders: a meta-analysis.
AB  - AIMS: To examine the effectiveness of contingency management (CM) techniques in
      treating substance use disorders (i.e. illicit drugs, alcohol, tobacco). DESIGN:
      Meta-analysis was used to determine the average effect size and potential
      moderators in 47 comparisons of the effectiveness of CM from studies based on a
      treatment-control group design and published between 1970 and 2002. FINDINGS: The
      mean effect size (ES) of CM was positive, with a magnitude of d = 0.42 using a
      fixed effects model. The magnitude of the ES declined over time, following
      treatment. CM was more effective in treating opiate use (d = 0.65) and cocaine
      use (d = 0.66), compared with tobacco (d = 0.31) or multiple drugs (d = 0.42).
      Larger effect sizes were associated with higher researcher involvement, earlier
      studies and shorter treatment duration. CONCLUSIONS: Study findings suggest that
      CM is among the more effective approaches to promoting abstinence during the
      treatment of substance use disorders. CM improves the ability of clients to
      remain abstinent, thereby allowing them to take fuller advantage of other
      clinical treatment components.

PMID- 17034435
TI  - Topiramate reduces the harm of excessive drinking: implications for public health
      and primary care.
AB  - AIMS: Having demonstrated previously the efficacy of topiramate--a sulfamate
      substituted fructopyranose derivative-as pharmacotherapy for treating alcohol
      dependence, promoting abstinence and reducing the harmful psychosocial
      consequences of drinking, we investigated whether topiramate also promoted 'safe'
      levels of drinking: < or = 1 and < or = 2 standard drinks/day for women and men,
      respectively, among alcohol-dependent individuals. DESIGN, SETTING AND
      PARTICIPANTS: In a double-blind, randomized, controlled, 12-week clinical trial
      conducted in San Antonio, Texas, 75 alcohol-dependent adults received topiramate
      and 75 received placebo as an adjunct to weekly standardized medication
      compliance management. MEASUREMENTS: For this secondary analysis of data from
      that trial, we calculated, based on self-reports, specific intervals of up to 30
      days of continuous 'safe' drinking for each subject. FINDINGS: The average
      longest 'safe' drinking period was 16.7 days for topiramate recipients versus 8.9
      days for placebo recipients. By day 50 of treatment, 44% versus 26.4% had
      achieved > or = 7 and 30.8% versus 10% had achieved > or = 14 continuous 'safe'
      drinking days. Similarly, topiramate increased the relative likelihood of
      continuous 'safe' drinking from 77% for > or = 7 days [relative risk (RR) for
      achieving continuous 'safe' drinking = 1.77] to threefold for > or = 14 days (RR
      = 3.37) and fourfold for > or = 28 days (RR = 4.07). Thus, participants who
      received topiramate were more likely to achieve longer periods of 'safe' drinking
      compared with those who received placebo. CONCLUSIONS: For alcohol-dependent
      individuals who drank within an abstinence-oriented treatment program, topiramate
      promoted 'safe' drinking. Topiramate's potential to decrease the public health
      consequences of hazardous drinking needs to be established in future long-term
      studies.

PMID- 17034436
TI  - Bad nights or bad bars? Multi-level analysis of environmental predictors of
      aggression in late-night large-capacity bars and clubs.
AB  - AIMS: To clarify environmental predictors of bar-room aggression by
      differentiating relationships due to nightly variations versus across bar
      variations, frequency versus severity of aggression and patron versus staff
      aggression. DESIGN, SETTING AND PARTICIPANTS: Male-female pairs of researcher
      observers conducted 1334 observations in 118 large capacity (> 300) bars and
      clubs in Toronto, Canada. MEASUREMENTS: Observers independently rated aspects of
      the environment (e.g. crowding) at every visit and wrote detailed narratives of
      each incident of aggression that occurred. Measures of severity of aggression for
      the visit were calculated by aggregating ratings for each person in aggressive
      incidents. FINDINGS: Although bivariate analyses confirmed the significance of
      most environmental predictors of aggression identified in previous research,
      multivariate analyses identified the following key visit-level predictors
      (controlling for bar-level relationships): rowdiness/permissive environment and
      people hanging around after closing predicted both frequency and severity of
      aggression; sexual activity, contact and competition and people with two or more
      drinks at closing predicted frequency but not severity of aggression; lack of
      staff monitoring predicted more severe patron aggression, while having more and
      better coordinated staff predicted more severe staff aggression. Intoxication of
      patrons was significantly associated with more frequent and severe patron
      aggression at the bar level (but not at the visit level) in the multivariate
      analyses and negatively associated with severity of staff aggression at the visit
      level. CONCLUSIONS: The results demonstrate clearly the importance of the
      immediate environment (not just the type of bar or characteristics of usual
      patrons) and the importance of specific environmental factors, including staff
      behaviour, in predicting both frequency and severity of aggression.

PMID- 17034437
TI  - Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use.
AB  - AIMS: To identify early onset cannabis users by measuring basal hypothalamic
      pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset
      substance use when showing low activity. DESIGN: In a prospective cohort study,
      adolescents who initiated cannabis use at an early age (9-12 years), those who
      initiated at a later age (13-14 years) and those who did not use cannabis by the
      age of 14 were compared with respect to HPA axis activity. SETTING AND
      PARTICIPANTS: Data were used from the first and second assessment wave of the
      TRacking Adolescents' Individual Lives Survey (TRAILS), that included 1768 Dutch
      young adolescents aged 10-12 years who were followed-up across a period of 2
      years. MEASUREMENTS: Cortisol was measured in saliva samples at awakening, 30
      minutes later and at 8 p.m. at age 10-12. Self-reported age at first cannabis use
      was used. FINDINGS: The early onset group had lower cortisol levels 30 minutes
      after awakening than the late onset group (OR = 0.93, 95% CI: 0.86-0.99).
      Furthermore, compared to non-users, the early and late onset cannabis users had
      higher levels of cortisol at 8 p.m. (OR = 1.25, 95% CI: 1.03-1.53 and OR = 1.21,
      95% CI: 1.01-1.45, respectively). CONCLUSIONS: Some evidence was found for HPA
      axis hypo-activity at awakening in adolescents with early onset of cannabis use
      compared to late onset users, which might indicate an increased risk for early
      onset users of seeking stimulation to restore arousal levels by using substances.

PMID- 17034438
TI  - Abstinence and moderate use goals in the treatment of marijuana dependence.
AB  - AIMS: The purpose of this study was to examine the influence of personal goals
      (abstinence or moderation) on treatment outcomes for marijuana use. Hypotheses
      regarding self-efficacy for goal attainment were tested. DESIGN: Adult marijuana
      users seeking treatment were assigned randomly to three treatment conditions: (1)
      cognitive-behavioral relapse prevention support group; (2) individualized brief
      motivational enhancement; and (3) delayed treatment control group. Follow-up
      assessments were conducted at 4, 7, 13 and 16 months. SETTING: University
      research offices. PARTICIPANTS: Participants were 291 adult marijuana users.
      Measurements Marijuana use, personal treatment goals and self-efficacy for
      achieving one's goal were assessed across the 16-month follow-up. FINDINGS:
      Greater marijuana related problems and dependence symptoms were associated with
      an initial goal of abstinence. Participants were more likely to achieve outcomes
      consistent with their personal goals. Participants with abstinence goals reported
      greater self-efficacy for goal achievement than those with moderation goals after
      participating in the abstinence oriented treatment; self-efficacy for goal
      success predicted goal achievement for both moderate use and abstinence goals.
      CONCLUSIONS: Marijuana users approaching an abstinence-oriented treatment varied
      in the extent to which they were actively seeking abstinence as the outcome.
      Differences in goals were predictable from severity of problems related to use.
      Goal preference and self-efficacy for achieving goals predicted outcomes. Future
      research should incorporate personal goals into treatment and assess their
      effects on outcomes.

PMID- 17034439
TI  - Enhanced recognition of facial expressions of disgust in opiate users receiving
      maintenance treatment.
AB  - AIMS: Accurate recognition of facial expressions of emotion is critical in
      interpersonal interaction but is impaired in alcoholics, even after a period of
      abstinence. Little is known of whether other drug-dependent populations also show
      these impairments. This study aimed to investigate facial expression recognition
      by chronic opiate users. DESIGN: An independent group design was used to compare
      20 participants receiving opiate substitution treatment, 20 ex-opiate users in
      rehabilitation (average abstinence of 6 months) and 21 unemployed healthy
      controls. MEASUREMENTS: The accuracy and speed of recognizing morphed emotional
      facial expressions were assessed using an emotional hexagon task. FINDINGS:
      Current opiate users were significantly more accurate than ex-users at
      recognizing expressions of disgust. They were also generally slower than controls
      in recognizing all expressions, and slower than ex-opiate users in recognizing
      surprise, happy and fearful expressions. CONCLUSIONS: Opiate users in maintenance
      treatment show a heightened ability to recognize facial expressions of disgust.
      We suggest that this may reflect increased exposure to other people's expressions
      of disgust and/or priming by the physical and social environments encountered by
      opiate-dependent individuals. Further, opiate maintained individuals' global
      slowness in processing emotional expressions may reflect the sedative effects of
      methadone.

PMID- 17034440
TI  - Cessation of injection drug use and change in injection frequency: the Chicago
      Needle Exchange Evaluation Study.
AB  - AIMS: To examine the effect of a needle exchange program (NEP) on incidence of
      injection cessation and change in injection frequency; to explore predictors for
      injection cessation and change in injection frequency; and to assess whether
      injection quitters transitioned to non-injected drug use. DESIGN AND SETTING:
      Between 1997 and 2002, 901 injection drug users (IDUs) were recruited from an NEP
      program or an area with no NEP in Chicago, Illinois, interviewed for drug use
      behaviors, tested for HIV and followed for three annual visits. All participants
      were exposed to prevention services targeting HIV and drug abuse. MEASUREMENTS:
      Injection cessation was defined as no injection drug use since the last
      interview, and changes in the number of injections in a typical month were
      examined. FINDINGS: Sixteen per cent of study participants reported stopping
      injection for a median duration of 16 months, and most of them also ceased rather
      than initiated the use of non-injected drugs. Those who continued injecting
      reduced their injection frequency by 12% per year, on average. Independent
      predictors of injection cessation were infrequent injection at baseline, younger
      age and injecting with others. NEP use was not associated with injection
      cessation and change in injection frequency. CONCLUSION: These results did not
      support the hypothesis that NEP use influences the frequency of injection over
      time. One-sixth of IDUs stopped injection for more than 1 year, providing a
      substantial window for relapse prevention interventions.

PMID- 17034441
TI  - Stimulant effects of 3,4-methylenedioxymethamphetamine (MDMA) 75 mg and
      methylphenidate 20 mg on actual driving during intoxication and withdrawal.
AB  - BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA) is currently one of the most
      popular drugs of abuse in Europe. Its increasing use over the last decade has led
      to concern regarding possible adverse effects on driving. The aims of the present
      study were to investigate the acute effects of MDMA on actual driving performance
      during the intoxication and withdrawal phase. METHODS: Eighteen recreational MDMA
      users (nine males, nine females) aged 21-39 years participated in a double-blind,
      placebo-controlled, three-way cross-over study. MDMA 75 mg, methylphenidate 20 mg
      and placebo were administered on day 1 of treatment (intoxication phase). Driving
      tests were conducted between 3 and 5 hours post-drug. Subjects returned the
      following day for a repetition of the driving tests between 27 and 29 hours post
      drug (withdrawal phase). On-the-road driving tests consisted of a road-tracking
      test and a car-following test. Its main parameters were standard deviation of
      lateral position (SDLP), time to speed adaptation (TSA), brake reaction time
      (BRT) and gain. FINDINGS: MDMA and methylphenidate significantly decreased SDLP
      in the road-tracking tests by about 2 cm relative to placebo on day 1
      (intoxication phase). In addition, MDMA intoxication decreased performance in the
      car-following test as indicated by a significant rise in the 'overshoot' of the
      subjects' response to speed decelerations of the leading vehicle. Driving
      performance was not affected by treatments during withdrawal on day 2.
      CONCLUSION: Collectively, these data indicate that MDMA is a stimulant drug that
      may improve certain aspects of the driving task, such as road-tracking
      performance, but may reduce performance in other aspects of the driving task,
      such as accuracy of speed adaptation during car-following performance.

PMID- 17034442
TI  - Use of crystal methamphetamine among gay men in London.
AB  - AIM: To examine the use of crystal methamphetamine (crystal meth) and its
      association with high-risk sexual behaviour among gay men in London. DESIGN:
      Cross-sectional surveys using self-administered questionnaires. SETTINGS:
      National Health Service (NHS) out-patient human immunodeficiency virus (HIV)
      treatment clinic in London; NHS HIV testing/sexual health clinics in London;
      central London gyms. PARTICIPANTS: HIV-positive gay men attending the HIV
      treatment clinic in 2002-03 (n = 388); HIV-negative gay men attending the HIV
      testing/sexual health clinics in 2002-03 (n = 266); gay men using the gyms
      between January and March 2003 (n = 445), 2004 (n = 653) and 2005 (n = 494).
      MEASUREMENTS: Percentage of gay men who reported: (i) using crystal meth in the
      previous 12 months; (ii) using other recreational drugs (e.g. cocaine, ecstasy,
      ketamine); (iii) high-risk sexual behaviour in the previous 3 months. FINDINGS:
      The percentage of gay men who had used crystal meth in the previous year varied
      by sample (HIV treatment clinic, 12.6%; HIV testing/sexual health clinics, 8.3%;
      gyms, 19.5%; P < 0.001) but did not change over time in the gyms (19.8%, 20.7%,
      17.8%; P = 0.5). In all samples, the majority of men used crystal meth only once
      or twice a year. Most crystal meth users (> 80%) had taken other recreational
      drugs. Crystal meth and other drug users were more likely to report high-risk
      sexual behaviour than other men, e.g. HIV treatment clinic sample: crystal meth
      users, 34.7%; other drug users, 18.9%, non-users, 10.6%, P < 0.001. Cause and
      effect could not be established. CONCLUSION: Among gay men in London surveyed in
      clinics, approximately one in 10 reported using crystal meth in the previous 12
      months (HIV-positive men 12.6%; HIV-negative men 8.3%). Most men used it
      infrequently--only once or twice a year. There was no evidence of increasing use
      of crystal meth between 2003 and 2005.

PMID- 17034443
TI  - A prospective cohort study on orally administered heroin substitution for
      severely addicted opioid users.
AB  - AIMS: To assess the efficacy and safety of orally administered heroin
      [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted
      opioid users. DESIGN: An open-label, prospective cohort study with two non
      randomly assigned treatment arms and historical controls: DAM tablets only versus
      DAM tablets combined with injected DAM and/or other opioids, with an observation
      period of 1 year. SETTING: Twenty-one out-patient treatment centres of the Swiss
      heroin-assisted treatment programme. PARTICIPANTS: A total of 128 patients
      received DAM tablets only, and 237 patients received a combination of orally and
      intravenously applied DAM and other opioids. MEASUREMENTS: Retention rate after 1
      year; number of serious adverse events; dosage of DAM over time; subjective
      tolerance of study medication. FINDINGS: In the intention-to-treat analysis, 1
      year retention rates after 1 year in the DAM tablets-only group [0.804, 95%
      confidence interval (CI) = 0.735-0.873] as well as in the subgroup combining oral
      application of DAM with intravenous application or other opioids (0.843, 95% CI =
      0.797-0.889) were higher compared to historical controls (Swiss cohort of
      patients who had been substituted intravenously with DAM; 1-year retention rate =
      0.70). Rates of serious adverse events under study medication (tablets only =
      0.038 per application year; tablets in combination = 0.028 per application year)
      were comparable to the historical rate of the Swiss heroin-assisted treatment
      (0.043). CONCLUSIONS: DAM tablets seem to be an effective and safe application
      mode of heroin-assisted substitution treatment. Randomized clinical trials to
      compare its relative efficacy to other substances are necessary.

PMID- 17034444
TI  - Doping in fitness sports: estimated number of unreported cases and individual
      probability of doping.
AB  - AIMS: Recent studies have suggested that the use of doping substances and
      particularly of anabolic androgenic steroids (AAS) is often practised by fitness
      centre visitors. These studies employed direct interview techniques and
      questionnaires to assess the estimated number of unreported cases of doping.
      Because people hesitate to provide compromising information about themselves,
      these techniques are subject to response errors. In this study we applied an
      alternative interview technique to assess more accurately unreported cases of
      doping in fitness centres. DESIGN AND PARTICIPANTS: The present investigation
      employed the randomized response technique (RRT) to reduce response errors. A
      cohort of 500 people from 49 fitness centres participated in this study. FINDING:
      The RRT revealed a high prevalence of doping (12.5%). In addition, and most
      importantly, the present RRT study revealed an alarmingly high prevalence of
      illicit drug use, specifically of cocaine use, that has been severely
      underestimated by previous studies. CONCLUSIONS: The RRT confirmed previously
      estimated rates of AAS use assessed by direct interview techniques and voluntary
      questionnaires, but uncovered a much higher usage rate of illicit drugs among
      fitness centre visitors. This outcome enabled us to construct a 'probability'
      rating for the use of doping substances in fitness centre visitors. Given its
      high prevalence and the predominant use of AAS, doping among fitness centre
      visitors is an issue of extreme relevance for the health care system. Our study
      may help to characterize further doping substance users and to develop and apply
      prevention and intervention programmes specifically to individuals at high risk.

PMID- 17034445
TI  - Social influences and self-efficacy as predictors of youth smoking initiation and
      cessation: a 3-year longitudinal study of vocational high school students in
      Taiwan.
AB  - AIMS: This 3-year longitudinal study examined changes in patterns of risk factors
      and protective factors of smoking initiation and cessation among vocational high
      school students in Taipei, Taiwan. DESIGN AND SETTING: In 2000, a total of 2151
      10th grade students from 16 vocational high schools were assessed and followed up
      in the 11th and 12th grades. Self-administered questionnaires were collected in
      each year to assess the pattern of changes in smoking behaviors, and risk and
      protective factors. FINDINGS: Of the 1654 non-smokers in the 10th grade, 227
      students initiated smoking by the 12th grade. Higher risk factors such as peer
      smoking, peers offering cigarettes, alcohol use and lower protective factors,
      such as refusal self-efficacy, antismoking attitude and belief in the 10th grade
      predicted youth initiation by grade 12. Increases in risk factors and decreases
      in protective factors during the years from 10th to 12th grades were associated
      significantly with youth smoking initiation. Of the 494 smokers in the 10th
      grade, 76 students quit smoking by the 12th grade. Lower risk factors and higher
      protective factors in 10th grade smokers predict youth smoking cessation by grade
      12. Decreases in risk factors and increases in protective factors were associated
      significantly with youth smoking cessation. CONCLUSIONS: The risk factors (i.e.
      social influences) and protective factors (i.e. self-efficacy) examined in this
      study predict both youth smoking initiation and youth smoking cessation.

PMID- 17034446
TI  - A randomized controlled trial to assess the effects of reimbursing the costs of
      smoking cessation therapy on sustained abstinence.
AB  - AIMS: We studied whether reimbursement for smoking cessation treatment (SCT) can
      increase prolonged abstinence from smoking up to 2 years. SETTING, PARTICIPANTS
      AND DESIGN: From the general population, we recruited smokers and assigned them
      randomly to a control group (n = 634) or an intervention group (n = 632). For 6
      months, participants in the intervention group could apply for reimbursement and
      received information regarding the reimbursed SCT. Participants in the control
      group received no reimbursement or information. MEASUREMENTS: In this follow-up
      study, prolonged abstinence from smoking was defined as reported being abstinent
      from at least 7 days before the end of reimbursement until the follow-up
      assessment 6 months or 2 years later. FINDINGS: At 6 months after the end of
      reimbursement, 18 participants in the control group (2.8%) and 35 participants
      (5.5%) in the intervention group reported sustained abstinence for at least 6
      months [odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.6]. Two years
      after the reimbursement period, 10 participants in the control group (1.6%) and
      27 participants in the intervention group (4.3%) still reported sustained
      abstinence (OR = 4.1, 95% CI 1.7-10.2). The overall effectiveness of SCT
      increased with reimbursement and was 22% in the intervention group and 8% in the
      control group after 2 years. CONCLUSIONS: Reimbursement may be an effective
      strategy to increase the prolonged abstinence rate even after 2 years.

PMID- 17034447
TI  - Addiction to apomorphine: a clinical case-centred discussion.
AB  - AIM: To report the case of a patient, who in the context of an anti-Parkinsonian
      therapy, developed addiction to apomorphine. METHODS: Clinical case description.
      RESULTS: Apomorphine is a dopaminergic agonist that acts directly on D2
      receptors. It has been used in alcoholism, male sexual dysfunction and with
      diagnostic and therapeutic purposes in Parkinson's disease (PD). CONCLUSIONS: The
      present work describes the case of a woman with PD who developed a loss of
      control over the consumption of apomorphine that resulted in a significant
      impairment of her functioning. PD patients with high frequency develop different
      psychiatric symptoms. Conversely, anti-Parkinsonian drugs also generate
      psychiatric symptoms that can be experienced by the patient as pleasant
      sensations ('alerting', 'awakening', 'activating', hypomania and hypersexuality).
      In spite of this, addiction to these drugs in patients with PD is a very rare
      phenomenon. Currently, the prescription of apomorphine has been extended to
      patients with erectile dysfunction, which may increase the prevalence of
      addiction cases or of severe psychiatric symptoms.

PMID- 17034448
TI  - Designer drugs as a cause of homicide.

PMID- 17034449
TI  - Canadian heroin supply and the Australian 'heroin shortage'.

PMID- 17034462
TI  - Biologic agents in psoriasis.
AB  - This paper reviews the new biologic agents that selectively block the immunologic
      steps implicated in the pathogenesis of psoriasis. Four strategies have been
      targeted: reduction of the number of pathogenic T cells; inhibition of T-cell
      activation and migration; modulation of the immune system; and blockage of the
      activity of inflammatory cytokines. There are three classes: monoclonal
      antibodies, fusion proteins and recombinant cytokines or growth factors. The
      actions, efficacy and side-effect profile of the biologic agents, alefacept,
      efalizumab, etanercept and infliximab, are reviewed.

PMID- 17034463
TI  - Non-Hodgkin lymphoma and skin cancer: A dangerous combination.
AB  - There is a significant association between non-Hodgkin lymphoma, including
      chronic lymphocytic leukaemia, and both melanoma and non-melanoma skin cancer.
      This review highlights the existing data on the phenomenon of accelerated skin
      cancer in patients with non-Hodgkin lymphoma and specifically chronic lymphocytic
      leukaemia. The outcomes of patients with non-Hodgkin lymphoma (including chronic
      lymphocytic leukaemia) and non-melanoma skin cancer are worse than in patients
      without concomitant lymphoreticular malignancy, as shown by increased rates of
      local recurrence, regional metastasis and death. Pathogenic factors may be common
      between non-Hodgkin lymphoma and chronic lymphocytic leukaemia and skin cancer.
      The treatment of skin cancer in patients with non-Hodgkin lymphoma must factor in
      the worse prognosis and adapt standard therapeutic approaches to minimize the
      risk of metastasis and death. Preventive strategies and early detection are
      paramount in this high-risk population.

PMID- 17034464
TI  - Development of a psychological treatment service for pruritic skin conditions.
AB  - The role of psychological contributions to common dermatological disease is
      increasingly recognized. It is often a challenge to find suitable psychological
      services to complement dermatological treatment. This paper describes the
      development of a psychological treatment service to reduce scratching behaviour
      found in common pruritic skin conditions. Our Department of Dermatology together
      with a consultation-liaison psychiatrist designed a four-session outpatient
      treatment programme incorporating psychiatric assessment, psychoeducation about
      the itch-scratch cycle, behavioural analysis, habit reversal techniques and
      between-session tasks for the patient to complete. This programme is actively
      modified in consultation with patients and their therapists to suit each
      patient's individual needs. Formal investigation is required to determine if this
      psychological treatment adds benefit in overall symptom control beyond
      dermatological treatment alone.

PMID- 17034465
TI  - Segmental haemangiomas of infancy: A review of 14 cases.
AB  - Haemangiomas of infancy are the commonest benign tumour in childhood, with the
      majority being a localized subtype, only requiring therapy in specific locations.
      The segmental subtype, however, confers a higher complication rate, an
      association with the PHACE syndrome and poorer prognosis. This retrospective case
      series of 14 infants with segmental haemangiomas aimed to further define the
      variety of clinical presentations, complication rates, and response to treatment
      in this subset of patients. We found in our series that 71% of infants with
      segmental haemangiomas develop at least one complication related to the lesion.
      Systemic corticosteroids prevented the further growth as well as reduced the pain
      and ulceration of the segmental haemangiomas in all of those treated. Early
      recognition and early treatment to arrest the growth of segmental haemangiomas
      will reduce morbidity and complications associated with these haemangiomas.
      Corticosteroid use, however, needs to be considered against the high incidence of
      side-effects such as secondary hypertension (40%), cushingoid features (40%) and
      growth suppression (67%). In our experience, these infants benefit from
      multidisciplinary team involvement for the assessment of associated syndromes,
      and to follow up and avoid complications associated with systemic therapy.

PMID- 17034466
TI  - Retrospective 5-year review of 131 patients with mycosis fungoides and Sezary
      syndrome seen at the National Skin Centre, Singapore.
AB  - A total of 131 new cases of mycosis fungoides and Sezary syndrome were diagnosed
      clinically and histopathologically at our centre over a 5-year period. There were
      87 males and 44 females with a mean age of 36.3 years (range 3-87 years) and no
      racial predilection. Of the 62 patients (47.3%) with classical mycosis fungoides,
      the majority were male (male : female = 4.2:1). There was one patient with Sezary
      syndrome. Patients aged older than 50 years were more likely to present with a
      longer duration of symptoms and advanced disease. In contrast to classical
      mycosis fungoides, the 47 patients diagnosed with hypopigmented mycosis fungoides
      had early stage disease, were younger, and no gender predilection was noted. The
      mean duration of follow up was 19.7 months (range 0.2-54.8 months). Complete
      remission was achieved in 24.7% and 53.8% of patients followed up at 1 and 3
      years, respectively, using skin-directed and systemic treatment modalities
      appropriate for the stage of disease. There were five patients with progressive
      disease and three patients with advanced disease who died from disease-related
      complications. The most significant prognostic factors for 1-year and 3-year
      outcomes were the patient's duration of symptoms and stage of disease at
      presentation.

PMID- 17034467
TI  - Leg crossers' dimple: A form of localized lipoatrophy.
AB  - We report eight individuals with localized lipoatrophy of the lateral lower leg
      that were seen by a single dermatologist in a 1-year period. All were
      asymptomatic and half had mild epidermal changes consistent with lichenification.
      Seven were an incidental finding during a general skin examination. All had a
      long-standing history of frequent leg crossing. The sites correlated with the
      area resting on the patella of the opposing knee. The depressions were larger on
      sides of leg-crossing preference. Only one had a significant rise in antinuclear
      antibodies, but this patient had no other clinical or serological abnormalities.
      This appears to be an extremely common yet previously unreported form of
      localized lipoatrophy.

PMID- 17034468
TI  - Two-year interim results from a 5-year study evaluating clinical recurrence of
      superficial basal cell carcinoma after treatment with imiquimod 5% cream daily
      for 6 weeks.
AB  - Imiquimod 5% cream is approved in the USA, Europe and Australia to treat
      superficial basal cell carcinoma, using a regimen of once daily, 5 times per week
      for 6 weeks. Vehicle-controlled, phase III clinical trials show that imiquimod is
      safe and effective for treating superficial basal cell carcinoma with dosing 5 or
      7 times per week for 6 weeks. This phase III, open-label study evaluates the long
      term (5 years) clinical efficacy and safety of dosing once daily, for which this
      manuscript reports the 2-year time point in the follow-up period. For the 169
      enrolled subjects, the tumour selected for treatment was assessed clinically to
      determine initial clearance at the 12-week post-treatment visit. If clinically
      clear of superficial basal cell carcinoma, subjects entered a 5-year, long-term
      follow-up period. Subjects were evaluated for recurrence at the 3-, 6-, 12- and
      24-month follow-up visits. The initial clearance rate at 12 weeks post treatment
      was 94.1%. The proportion of subjects who were clinically clear at the 2-year
      follow-up visit was estimated to be 82.0%. Imiquimod was tolerated when applied
      daily, with erythema reported for all subjects participating in the study. The
      recurrence rate observed suggests that once daily dosing and 5x/week dosing yield
      similar clearance rates, but daily dosing increases local skin reactions.

PMID- 17034469
TI  - Muir-Torre syndrome: Diagnostic and screening guidelines.
AB  - A 65-year-old man presented with a history of multiple skin coloured papules on
      his face that were asymptomatic. He had an adenocarcinoma resected from his
      proximal colon 12 years prior to presentation as well as a family history of
      colon cancer on the maternal side. Diagnostic biopsies showed the lesions to be
      sebaceous adenomas and epitheliomas and the diagnosis of Muir-Torre syndrome was
      made. The sebaceous tumour tissue showed microsatellite instability and
      immunohistochemical staining indicated diminished expression in the DNA mismatch
      repair protein complex MSH2/MSH6. Genetic analysis showed a germline mutation in
      the MSH2 gene confirming the diagnosis of Muir-Torre syndrome. The patient and
      his first-degree relatives have been referred for genetic counselling and
      screening. We review the diagnostic criteria in this syndrome and review the
      recommended screening guidelines.

PMID- 17034470
TI  - Allopurinol induced generalized eosinophilic pustular folliculitis.
AB  - A 71-year-old Cambodian man who was commenced on allopurinol for the treatment of
      gout developed a generalized papulopustular follicular eruption 8 weeks following
      introduction of the drug. The skin biopsy findings were consistent with that of
      eosinophilic pustular folliculitis. Resolution of the rash took place during the
      8 weeks following cessation of allopurinol and treatment with oral and topical
      corticosteroids.

PMID- 17034471
TI  - The syndrome of hereditary leiomyomatosis and renal cell cancer (HLRCC): The
      clinical features of an individual with a fumarate hydratase gene mutation.
AB  - A 55-year-old woman presented with multiple cutaneous leiomyomas and multiple
      uterine leiomyomas (fibroids). The clinical diagnosis of the autosomal dominant
      hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome was confirmed by
      identification of a fumarate hydratase gene mutation. This case highlights the
      need to consider the possibility of renal and uterine cancer in members of
      cutaneous leiomyomatosis families.

PMID- 17034472
TI  - Metastatic Bowen carcinoma.
AB  - A 72-year-old man presented with basaloid squamous cell carcinoma metastatic to
      both lungs that was morphologically similar to recurrent, invasive moderately to
      poorly differentiated carcinoma arising from persistent Bowen's disease of the
      right cheek. The original lesion of invasive moderately differentiated squamous
      cell carcinoma arising in Bowen's disease had been excised 11 years previously.
      Mohs' surgery was performed for the recurrent lesion on the cheek 12 months prior
      to detection of lung metastases. He died of respiratory failure 19 months
      following diagnosis of his metastatic disease. Our case reflects the potentially
      aggressive nature of invasive squamous cell carcinoma arising from Bowen's
      disease and highlights the importance of approaching this entity with a view to
      complete surgical excision with adequate margins.

PMID- 17034473
TI  - Successful treatment of recalcitrant necrotizing eosinophilic folliculitis using
      indomethacin and cephalexin.
AB  - A 56-year-old man presented with a 4-month history of a painful and pruritic
      eruption consisting of crusted plaques and blisters on his face, scalp and chest.
      The patient suffered from headaches and malaise but was afebrile. Two skin
      biopsies revealed an epidermis which was eroded and covered by locules of serum
      and neutrophils. In the underlying dermis, there was a marked mixed inflammatory
      reaction including lymphocytes, neutrophils and numerous eosinophils. There was
      exocytosis of eosinophils into several follicles with areas of follicular
      mucinosis. A diagnosis of necrotizing eosinophilic folliculitis was made based
      upon the clinical and histopathological findings. The diagnosis was supported by
      the rapid response to a combination of indomethacin and cephalexin. The patient
      has taken continuous indomethacin (with rabeprazole and misoprostol cover) and
      cephalexin for 2 years. If treatment is withdrawn he experiences a flare of his
      disease within 2 weeks. This case highlights the potentially chronic nature of
      this disease.

PMID- 17034474
TI  - Parvovirus B19 infection presenting as 'bathing trunk' erythema with pustules.
AB  - A 7-year-old girl presented with acute vulval erythema and pustules, associated
      with a petechial eruption in her flexures and over her feet. There was a mild
      prodromal illness and the patient was afebrile. There were minimal symptoms
      associated with the rash. Skin and throat swabs were negative and blood
      examination showed mild neutrophilia and lymphopaenia. Parvovirus B19 IgM was
      detected on serology and cutaneous features resolved within 4 days. This is a
      further case of parvovirus B19 infection presenting as a 'bathing trunk' exanthem
      that has unique dermatologic features, including the presence of pustules and
      distant petechiae.

PMID- 17034475
TI  - Prurigo pigmentosa.
AB  - A 22-year-old Chinese woman presented with a 5-year history of an intensely
      pruritic eruption on her posterior neck, mid back and sacrum leaving reticulate
      pigmentation. The diagnosis of prurigo pigmentosa was made on the basis of the
      clinico-histological features and a response to minocycline. Although prurigo
      pigmentosa is uncommon, it has characteristic clinical and histological features.
      Early diagnosis and appropriate treatment result in a rapid response and prevents
      a progression of pigmentation.

PMID- 17034476
TI  - Primary cutaneous diffuse leiomyosarcoma with desmoplasia.
AB  - A 65-year-old man presented with an indurated plaque over his left cheek and left
      neck. An initial punch biopsy of skin showing increased smooth muscle bundles was
      consistent with a diagnosis of smooth muscle hamartoma. A second incisional skin
      biopsy revealed a well-differentiated smooth muscle proliferation invading into
      the dermis and subcutaneous fat in a diffusely infiltrative pattern and with a
      desmoplastic component, suggesting a diagnosis of desmoplastic leiomyosarcoma.
      Resection of the tumour confirmed the presence of a cytologically low grade
      leiomyosarcoma with an insidious infiltrative growth pattern. This rare pattern
      of diffuse leiomyosarcoma is important to recognize as the histological features
      are subtle and may potentially constitute a pitfall in histological diagnosis in
      a small biopsy specimen. In addition, our case illustrates overlapping morphology
      between diffuse and desmoplastic types of leiomyosarcoma.

PMID- 17034477
TI  - Chondrocutaneous advancement flap for reconstruction of helical rim defects in
      dermatologic surgery.
AB  - The helical rim is often affected with cutaneous malignancies and requires
      special attention in the repair, owing to the complex cartilaginous contour,
      preservation of the aesthetic contour and restoration of its supportive function
      for eyeglasses and hearing aids. We review the surgical technique of
      chondrocutaneous advancement flap described by Antia and Buch as one of the most
      cosmetically appealing and versatile approaches for the repair of small defects
      of the ear helix.

PMID- 17034478
TI  - Cheilitis caused by contact allergy to anethole in spearmint flavoured
      toothpaste.
AB  - A 63-year-old woman presented with a 6-year history of persistent cheilitis.
      Minimal improvement was achieved with therapeutic measures. Patch testing was
      positive to anethole, a flavouring used in her toothpaste. Her cheilitis resolved
      after cessation of the flavoured toothpaste. This case demonstrates the
      importance of considering contact allergy to toothpaste flavours in patients with
      cheilitis.

PMID- 17034489
TI  - Development of a cell-isolation method for human prostatic smooth muscle cells
      based on cell type-specific activation of the SM22 gene promoter.
AB  - OBJECTIVE: To separate smooth muscle cells (SMCs) from fibroblasts in cultured
      human prostatic stromal cells (PrSCs) by characterizing the SM22 promoter as a
      prostatic SMC-specific gene promoter, and to investigate its use for a promoter
      based cell-sorting method, as SMCs are critical for stromal function and the
      pathological changes in the development of benign prostatic hyperplasia.
      MATERIALS AND METHODS: Human PrSCs were cultured in SMC-selective medium or
      standard medium, respectively, to obtain typical cultures of SMCs and
      fibroblasts. SM22 promoter activity and specificity were analysed by luciferase
      reporter-gene assay. A dual-colour vector was constructed with the expression of
      the red fluorescent protein (RFP) under the control of the 1.4 kb SMC-specific
      SM22 promoter, and the expression of the green fluorescent protein (GFP) under
      cytomegalovirus promoter. Fluorescence-activated cell sorting (FACS) was used to
      isolate and enrich GFP+/RFP+ and GFP+/RFP- cells. Cell phenotype was confirmed by
      reverse transcription-polymerase chain reaction and immunofluorescence. RESULTS:
      The 1.4 kb SM22 promoter activity was much higher in PrSCs cultured in SMC
      selective medium. Immunofluorescence staining and merged fluorescence microscopy
      ensured that SM22 promoter-driven GFP positive cells were SMCs. After
      transfection of the dual-colour vector into PrSCs, GFP+/RFP+ cells (SMCs) and
      GFP+/RFP- cells (fibroblasts) were isolated by FACS. The phenotype of FACS
      enriched SMCs and fibroblasts was confirmed. CONCLUSION: These results indicate
      that the 1.4 kb SM22 promoter is specific for prostatic SMCs. This dual-colour
      vector could be a useful tool for separating living SMCs from fibroblasts using
      FACS.

PMID- 17034490
TI  - Sigmoid orthotopic neobladder after radical cystectomy for bladder tumour: an
      Indian experience.
AB  - OBJECTIVE: To determine the long-term results of constructing a sigmoid
      neobladder after radical cystectomy for transitional cell carcinoma (TCC) of the
      urinary bladder. PATIENTS AND METHODS: The study included 170 patients with TCC
      of the bladder and a normal sigmoid colon. After radical cystectomy the
      neobladder was formed by completely detubularizing an isolated sigmoid colon
      segment. Subsequently patients were followed by clinical, biochemical,
      radiological and urodynamic assessments. RESULTS: Four patients died soon after
      surgery; the neobladder-related delayed complications were death in three
      patients, loss of five renal units, and electrolyte imbalance in five patients.
      Uretero-intestinal anastomotic narrowing was another frequent delayed
      complication. Most (97%) patients had nocturnal incontinence, and most voided
      with a good stream with a minimal postvoid residual urine volume. CONCLUSION: The
      sigmoid neobladder, despite some limitations, is the best option for diverting
      urine after radical cystectomy.

PMID- 17034491
TI  - Could a rural lifestyle decrease the prevalence of erectile dysfunction?
AB  - OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in a specific
      population and explore potential correlates with lifestyle. SUBJECTS AND METHODS:
      This prospective observational study, covering a population of a very small rural
      town, included 2000 men aged > or = 20 years from a total population of 121 831
      (51% female and 49% male). The International Index of Erectile Function was
      completed by each of the 2000 men at their homes over a 1-year period. Another
      questionnaire assessing socio-economic status and health-related determinants of
      ED were also completed. RESULTS: All 2000 men completed the questionnaires;
      overall, only 34 reported ED (1.7%). The frequency of mild, mild to moderate,
      moderate and severe ED was 12%, 29%, 20% and 38%, respectively. Significantly
      more men aged > 51 years had ED than those aged <41 years (0.05% and 0.45%,
      respectively; P < 0.001). There was no difference in ED with salary levels.
      CONCLUSION: The prevalence of ED in this particular rural population of Brazil
      was very low, at only 1.7%. Although ED increases with age, this association was
      not apparent for all age groups. It seems that several others factors, e.g.
      lifestyle, culture and diet, could be important for the onset of ED.

PMID- 17034492
TI  - Sperm banking: use and outcomes in patients treated for testicular cancer.
AB  - OBJECTIVE: To identify the frequency that sperm banking was used by men being
      treated for testicular cancer at our institution, and to characterize the
      differences between men choosing to bank sperm or not, and outcomes in terms of
      after-treatment pregnancies. PATIENTS AND METHODS: A questionnaire addressing
      sperm banking and fertility was administered to men treated for testicular cancer
      at our institution between 1994 and 2004; the results were evaluated
      statistically. RESULTS: Overall, 31 of 129 (24%) respondents had banked sperm. Of
      these, two had used their banked sperm to father a child, and 12 had had children
      naturally. Men who banked sperm were a mean of 10.3 years younger (P < 0.001) and
      less likely to have children at the time of diagnosis (P < 0.025) than men
      choosing not to bank sperm. The cost of banking sperm was reported to include a
      mean fee of US dollars 358 (median 300, range 0-1000), and a mean annual
      maintenance fee of US dollars 243.86 (median 300, range 0-1200). CONCLUSIONS:
      Only a minority of men in this study chose to bank sperm (24%). Among those who
      did, the use of banked sperm was low (<10%), and many men could have children
      without using banked sperm. Given the relatively high costs of sperm banking and
      the low rate of sample use, patients should be counselled on the costs and
      benefits of sperm banking before treatment for testicular cancer.

PMID- 17034493
TI  - Three-dimensional ultrasonography of the urinary bladder: preliminary experience
      of assessment in patients with haematuria.
AB  - OBJECTIVE: To assess the value of three-dimensional (3D) vs two-dimensional (2D)
      ultrasonography (US) in the diagnostic evaluation of the urinary bladder in
      patients with haematuria. PATIENTS AND METHODS: In all, 42 patients with painless
      haematuria and/or irritative voiding symptoms were examined with 2D- and 3D-US.
      US was done with an Acuson Sequoia unit (Siemens Medical Sol. Mountain View, CA,
      USA) and the Perspective(R) 3D technique, to assess the presence of bladder
      lesions, including bladder cancer, bladder wall hypertrophy with trabeculation
      and diverticula, mucosal bladder folds or re-growth of the prostate mimicking a
      bladder tumour. The imaging findings were compared with cystoscopy and/or bladder
      biopsy. RESULTS: In 21 of the 42 patients (50%) cystoscopy with bladder biopsy
      revealed bladder cancer. Overall, 3D-US gave a correct diagnosis for 36 of 42
      patients (86%). All 21 bladder cancers were correctly diagnosed, and 15 (71%) of
      the 21 benign bladder lesions were correctly identified. By contrast, 2D-US
      findings gave suspected bladder cancer in all patients. CONCLUSIONS: 3D-US is
      significantly more accurate than standard 2D-US in the diagnostic evaluation of
      patients with haematuria. Thus, this diagnostic technique might be useful for
      routine evaluation of the urinary bladder.

PMID- 17034494
TI  - Melatonin rhythm in children with enuresis.
AB  - OBJECTIVE: To study the circadian rhythm of melatonin in children with enuresis.
      PATIENTS AND METHODS: Twenty-five children, divided into two groups (enuretic
      patients and controls) were assessed; salivary samples were collected to measure
      melatonin by radioimmunoassay using commercial kits. Friedman two-way anova and
      Wilcoxon tests were used to assess the circadian rhythm of melatonin, and anova
      with between-patient factors and Mann-Whitney tests to compare melatonin values
      and groups. RESULTS: Both groups had statistically significant differences in
      melatonin concentration during the 24-h period (both P < 0.001), with a circadian
      rhythm; the highest values were always at approximately 04.00 hours. There were
      no significant differences overall in melatonin values between cases and
      controls, but patients had lower peak values than controls at 04.00 hours, and
      higher melatonin levels at 24.00 hours, but with no significant differences.
      CONCLUSION: There was some evidence for minor disturbances in the circadian
      rhythm of melatonin as a cause of enuresis, but the rhythm was not grossly
      disrupted.

PMID- 17034495
TI  - Effect of chronic lithium administration on endothelium-dependent relaxation of
      rat corpus cavernosum: the role of nitric oxide and cyclooxygenase pathways.
AB  - OBJECTIVE: To verify the effect of chronic lithium administration on the
      endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major
      drug for treating bipolar disorder and some studies showed that lithium might
      cause erectile dysfunction in such patients, by a mechanism as yet unknown.
      MATERIALS AND METHODS: LiCl (600 mg/L) was dissolved in drinking water and
      Sprague-Dawley rats received the solution for 30 days; control rats received tap
      water. After 30 days corporeal strips were prepared from both groups, mounted
      under tension in oxygenated organ baths, and pre-contracted with phenylephrine
      (7.5 microm). After equilibration, the strips were relaxed by acetylcholine (10
      nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase
      inhibitor; 20 microm). Furthermore, the relaxant responses to sodium
      nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in
      both groups. NADPH-diaphorase histochemistry was used to identify NO synthase
      within cavernosal tissue strips of both groups. RESULTS: The acetylcholine
      dependent relaxation was significantly lower in lithium-treated rats than in
      controls. Although indomethacin decreased significantly the relaxant responses to
      acetylcholine in controls, it increased the relaxant responses in lithium-treated
      rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than
      in control preparations. Sodium nitroprusside produced similar relaxation in both
      groups. CONCLUSION: Chronic lithium administration can impair the endothelium
      dependent relaxation of rat corpus cavernosum; NO availability might decrease
      after lithium administration and the cyclooxygenase pathways might have a role in
      this effect.

PMID- 17034496
TI  - Palliative transurethral resection of the prostate: functional outcome and impact
      on survival.
AB  - OBJECTIVE: To assess the long-term functional and oncological outcome in a
      consecutive series of patients undergoing palliative transurethral resection of
      the prostate (pTURP). PATIENTS AND METHODS: We retrospectively assessed all
      patients who had a pTURP between 1992 and 2004 at our institution. Patients with
      incidental prostate cancer (pT1a/pT1b) were excluded. In all, 89 patients (mean
      age 75.9 years, sd 0.9, at diagnosis) entered the study. RESULTS: The median
      (range) prostate-specific antigen level at diagnosis was 25.7 (0.7-5000) ng/mL
      and the mean Gleason score was 7. The mean (sd, range) interval between the
      diagnosis of prostate cancer and pTURP was 1.5 (0.3, 0.5-10.9) years. The
      indications for pTURP were refractory urinary retention in 30%, severe bladder
      outlet obstruction with a postvoid residual urine volume of > 100 mL in 43%, and
      bladder stones, haematuria and hydronephrosis in 9% each. The mean (sd, range)
      follow-up after pTURP was 2.6 (0.2, 0.1-7.3) years. The peri-operative mortality
      (<30 days) was 2%, and 22 patients (25%) died during the follow-up. As estimated
      by Kaplan-Meier analysis, the 1-, 2- and 5-year survival rates were 83%, 70% and
      61%, respectively. Patients with prostate cancer in the pTURP specimen had a
      shorter 3-year survival (52%) than those with a negative histology (89%, P =
      0.03). At the last follow-up, 79% of men voided spontaneously and were continent.
      A repeat pTURP was necessary in 25% of patients, 11% required permanent
      catheterization and 10% were incontinent. CONCLUSION: Despite greater peri
      operative mortality and morbidity than conventional TURP, pTURP is a fairly safe
      and effective procedure. Although a potential negative impact of pTURP on
      survival cannot be excluded, the estimated 5-year survival of 61% in this series
      seems to justify this intervention.

PMID- 17034497
TI  - Functional urinary and fecal incontinence in neurologically normal children:
      symptoms of one 'functional elimination disorder'?
AB  - OBJECTIVE: To clarify the relationship between disordered defecation and non
      neuropathic bladder-sphincter dysfunction (NNBSD) by comparing the prevalence of
      symptoms of disordered defecation in children with NNBSD before and after
      treatment for urinary incontinence (UI), and assessing the effect of such
      symptoms on the cure rate for UI. PATIENTS AND METHODS: In the European Bladder
      Dysfunction Study, a prospective multicentre study comparing treatment plans for
      children with NNBSD, 202 children completed questionnaires on voiding and on
      defecation, at entry and after treatment for UI. Four symptoms of disordered
      defecation were evaluated; low defecation frequency, painful defecation, fecal
      soiling, and encopresis. RESULTS: At entry, 17 of the 179 children with complete
      data sets had low defecation frequency and/or painful defecation (9%), classified
      as functional constipation (FC). Of the 179 children, 57 had either isolated
      fecal soiling or soiling with encopresis (32%), classified as functional fecal
      incontinence (FFI). After treatment for UI, FFI decreased to 38/179 (21%)
      (statistically significant, P = 0.035); for FC there were too few children for
      analysis. After treatment for UI, 19 of the 179 children (11%) reported de novo
      FFI. Symptoms of disordered defecation did not influence the cure rate of
      treatment for UI. CONCLUSIONS: FFI improved significantly after treatment for UI
      only, but not in relation to the outcome of such treatment. FFI did not influence
      the cure rate for UI. There was little to support a causal relation between
      disordered defecation and NNBDS ('functional elimination syndrome').

PMID- 17034498
TI  - Prevalence and correlations of lower urinary tract symptoms, erectile dysfunction
      and incontinence in men from a multiethnic Asian population: Results of a
      regional population-based survey and comparison with industrialized nations.
AB  - OBJECTIVE: To determine, in a population-based survey, the prevalence of lower
      urinary tract symptoms (LUTS), erectile dysfunction (ED) and incontinence in
      community-dwelling men in multiethnic Malaysia, as currently available Western
      demographic data might not be applicable in the Asian population. SUBJECTS AND
      METHODS: A cross-sectional population-based survey was carried out in the State
      of Penang, Malaysia, with a target population of men aged > or = 40 years. Using
      a multistage study design, random systematic sampling was used to represent the
      target population, who were weighted based on ethnicity and rural-urban ratios so
      as to represent the general population distribution. Trained field-workers
      conducted direct interviews and administered the American Urological Association
      Symptom Index (AUA-SI), the International Index of Erectile Function (IIEF-5)
      questionnaire and questions on incontinence based on the International Continence
      Society 2002 definition. RESULTS: In all, 418 men aged > or = 40 years were
      interviewed, of whom 353 completed the AUA-SI questionnaire (84.5% response
      rate). The prevalence of mild, moderate and severe LUTS was 80.6%, 6% and 0.3%,
      respectively. The prevalent symptoms were frequency and nocturia. There was
      moderate and severe ED in 45.9% of men, whereas incontinence was reported by
      8.2%. The AUA-SI correlated strongly with age (R = 0.291, P < 0.001), IIEF-5 (R =
      - 0.265, P < 0.001) and diabetes mellitus. CONCLUSION: The prevalence and
      severity of LUTS, ED and incontinence increased with age in this multiethnic
      Asian population, in which ED correlated strongly with LUTS. Compared to the
      Western population, the prevalence of LUTS was significantly lower, while the
      prevalence of ED and incontinence were comparable.

PMID- 17034499
TI  - High-intensity focused ultrasound for treating prostate cancer.

PMID- 17034500
TI  - Different brain effects during chronic and acute sacral neuromodulation in urge
      incontinent patients with implanted neurostimulators.
AB  - OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using
      positron emission tomography (PET), during chronic and acute sacral
      neuromodulation (SN). SN is an effective long-term treatment for chronic urge
      incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and
      supraspinal structures are probably responsible for the action of SN. It is not
      known which brain areas are involved, and the optimum benefit of SN is not
      immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS
      AND METHODS: Brain activity was measured in two groups: 12 urge incontinent
      patients (11 women and one man; mean age 52 years) in whom an implanted
      unilateral S3 nerve neurostimulator had been effective for >6 months (mean time
      after implantation 4.5 years); and eight urge incontinent patients (seven women
      and one man; mean age 49 years) in whom the neurostimulator was activated for the
      first time in the PET scanner. RESULTS: During SN in chronically implanted
      patients, there were significant decreases in rCBF in the middle part of the
      cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent
      midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex.
      During acute SN in newly implanted patients, there were significant decreases in
      rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex,
      the right insular cortex and the ventromedial orbitofrontal cortex. Group
      analysis between chronic and newly implanted patients showed significant
      differences in the associative sensory cortex, premotor cortex and the
      cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings
      suggests that chronic SN influences, presumably via the spinal cord, brain areas
      previously implicated in detrusor hyperactivity, awareness of bladder filling,
      the urge to void and the timing of micturition. Furthermore, SN affects areas
      involved in alertness and awareness. Acute SN modulates predominantly areas
      involved in sensorimotor learning, which might become less active during the
      course of chronic SN.

PMID- 17034501
TI  - Biochemical (prostate-specific antigen) relapse-free survival and toxicity after
      125I low-dose-rate prostate brachytherapy.
AB  - OBJECTIVE: To report our clinical experience and 5-year prostate-specific antigen
      (PSA) relapse-free survival rate for early-stage prostate cancer after (125)I low
      dose-rate prostate brachytherapy. PATIENTS AND METHODS: In all, 300 patients were
      treated between March 1999 and April 2003, and followed prospectively. Patients
      were stratified into low-, intermediate- and high-risk groups, and those
      receiving neoadjuvant androgen deprivation (NAAD) or not. Kaplan-Meier estimates
      of PSA relapse-free survival and PSA nadirs were obtained for all patients and
      for the risk groups. Toxicity, as urinary and erectile dysfunction (ED), were
      reported from a prospective database. RESULTS: The median (range) follow-up was
      45 (33-82) months. The actuarial PSA relapse-free survival was 93% at 5 years; 21
      (7%) of patients had evidence of biochemical failure as defined by the American
      Society of Therapeutic Radiation Oncology criteria. There was no significant
      difference in actuarial survival for patients in the different risk groups, or
      between those receiving NAAD or not (low-risk 96%, intermediate 89%, high 93%, P
      = 0.12; NAAD 92%, no NAAD 95%, P = 0.30). Overall the 3-year median PSA level was
      0.3 ng/mL (192 men). There was no significant difference in median 3-year PSA
      levels for different risk groups, or for those treated with or with no NAAD. The
      3- and 4-year PSA nadir of <0.5 ng/mL was achieved by 71% and 86% of men,
      respectively. The acute urinary retention rate was 7%; 5.6% of men developed
      urethral strictures requiring dilatation, while 2.7% required a transurethral
      resection of the prostate after implantation, for obstructive symptoms. Of
      patients with no ED before treatment, 62% had no ED at 2 years, and of these 60%
      used a phosphodiesterase inhibitor. CONCLUSION: This prospective series confirms
      the excellent overall biochemical survival after (125)I brachytherapy; the
      treatment was tolerated well, with early and late urinary toxicity and ED similar
      to other published results.

PMID- 17034502
TI  - Growth curves of the fetal prostate based on three-dimensional reconstructions: a
      correlation with gestational age and maternal testosterone levels.
AB  - OBJECTIVE: To create a nomogram of the fetal growth of the human prostate
      corresponding to gestational age, and to investigate the relationship between the
      expansive growth of the fetal prostate and the maternal testosterone surge during
      pregnancy. MATERIALS AND METHODS: In all, 27 fetal prostates at 11-40 weeks of
      gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed.
      Serial sections of prostates were immunostained and examined using light
      microscopy. After modular image acquisition the volumes were calculated using
      three-dimensional reconstruction. The prostate volumes were correlated with
      gestational age, and related to reference testosterone levels during pregnancy.
      RESULTS: There was exponential growth of the fetal prostate with gestational age.
      The increasing volume of the prostate during the fetal period corresponded with
      maternal testosterone levels. In the second trimester there was a significant
      increase in prostate volume in relation to the bladder. In infants,
      macroscopically there was an inverse proportion between bladder size and prostate
      volume. CONCLUSIONS: Starting from the second trimester there is distinct growth
      of the fetal prostate, obviously triggered by the maternal testosterone surge. In
      neonates there is an inversion of the dimensions between bladder and prostate.
      These results indicating exponential growth of the fetal prostate provide
      evidence of a gender-related transient infravesical obstruction in human fetuses.

PMID- 17034503
TI  - The use of prostate-specific antigen testing in men presenting with haematuria.
AB  - OBJECTIVES: To analyse prostate-specific antigen (PSA) levels and clinical
      outcome in men presenting with haematuria, to develop an evidence-base for the
      use of PSA testing in this setting, as haematuria is a known complication of
      locally invasive prostate cancer, and so PSA levels are often measured in
      patients presenting with haematuria. PATIENTS AND METHODS: We reviewed the
      records of 637 men presenting with haematuria to our urology department between
      April 2002 and June 2005. RESULTS: Of 373 men aged 50-79 years, 278 (75%) had
      their PSA level measured, and 50 were abnormal. Prostate biopsies were taken in
      27 men with an abnormal PSA level (54%) and one man with a normal PSA level but
      an abnormal digital rectal examination. Prostate cancer was detected in 22
      patients (8% of those tested, and 71% of those biopsied); 4.7% of all men
      presenting with macroscopic haematuria and aged 50-79 years were found to have
      prostate cancer, vs 8.5% of those with microscopic haematuria. CONCLUSIONS: We
      report a higher proportion of prostate cancers in men presenting with haematuria
      and aged 50-79 years than reported in previous screening studies, and a cancer
      detection rate of 71% of those biopsied, which is at least double the detection
      rates seen in screening studies. In the absence of a prospective controlled
      trial, PSA testing will remain part of our protocol for both macroscopic and
      microscopic haematuria.

PMID- 17034504
TI  - An immunohistochemical study of chromogranin A and human epidermal growth factor
      2 expression using initial prostate biopsy specimens from patients with bone
      metastatic prostate cancer.
AB  - OBJECTIVES: To investigate, using prostate needle-biopsy specimens at diagnosis
      from patients with bone metastatic prostate cancer, whether the relationship
      between neuroendocrine (NE) cell differentiation and human epidermal growth
      factor-2 (HER-2) expression is a prognostic factor for outcome. PATIENTS AND
      METHODS: The study included 50 patients diagnosed as having bone metastatic
      prostate cancer between January 1998 and December 2001. We tested for NE cell
      differentiation by using immunohistochemical (IHC) staining for chromogranin A
      (CgA), and for HER-2, using a commercial test for IHC staining. RESULTS: Eleven
      patients (22%) were positive for CgA; there was a significant difference in the
      time to recurrence (P = 0.025) but no significant differences in cause-specific
      survival rate or survival rate after recurrence. In all, 21 patients (42%) were
      positive for HER-2; the cause-specific survival rate, time to recurrence and
      survival rate after recurrence were all significantly more favourable in the HER
      2-negative group (P = 0.008, 0.049 and 0.025, respectively). In the 49 patients
      for whom both factors could be determined, there was no significant correlation
      between CgA and HER-2 positivity. CONCLUSIONS: NE cell differentiation of the
      primary tumour in patients with bone metastatic prostate cancer does not reflect
      the prognosis, whereas HER-2 overexpression is a prognostic factor for an
      unfavourable outcome. These results suggest that NE cell differentiation is not
      induced by HER-2.

PMID- 17034505
TI  - Complications and neobladder function of the Hautmann orthotopic ileal
      neobladder.
AB  - OBJECTIVE: To report the complications and function of the Hautmann orthotopic
      ileal neobladder . PATIENTS AND METHODS: In a 6.5-year period, 67 patients had an
      ileal neobladder constructed after radical cystectomy as treatment for invasive
      carcinoma of the bladder. All complications were reported systematically.
      Neobladder function was assessed by patient interviews, uroflowmetry and
      cystometric analyses. RESULTS: There were early complications in 41 patients
      (61%), and late complications in 32 (48%); 23 (34%) had both early and late
      complications and 17 (25%) had none. Eighteen of the patients (27%) required a re
      operation for complications. At the 4-month follow-up, 90% were continent during
      the day and 65% during the night; at 1 year after surgery 95% were continent
      during the day and 73% during the night. The functional bladder capacity and
      maximum cystometric capacity were close to the natural bladder volume (median 450
      and 480 mL, respectively). CONCLUSIONS: Despite the high rate of complications in
      this study, most were considered as minor and could be treated by conservative or
      minimally invasive methods. The neobladder had an acceptable resemblance to the
      native bladder in capacity and function. Consequently the ileal neobladder might
      be preferred as a urinary diversion after radical cystectomy, if no
      contraindications are present.

PMID- 17034506
TI  - Surgical volume is related to the rate of positive surgical margins at radical
      prostatectomy in European patients.
AB  - OBJECTIVE: To assess the association between surgical volume (SV) and the rate of
      positive surgical margins (PSM) after radical prostatectomy (RP) in a large
      single-institution European cohort of patients. PATIENTS AND METHODS: In all,
      2402 men had a RP by a group of 11 surgeons, all of whom were trained by the
      surgeon with the highest SV; all surgeons used the same surgical technique.
      Variables assessed before RP were prostate-specific antigen (PSA) level, clinical
      stage and biopsy Gleason sum; variables assessed after RP were PSA level,
      extracapsular extension, seminal vesicle invasion, lymph node invasion and
      pathological Gleason sum. These were used to predict the rate of PSM in models
      before or after RP. Multivariate models were complemented with SV to test its
      independent and multivariate statistical significance and to quantify its impact
      on the model's overall (and 200 bootstrap-corrected) predictive accuracy.
      RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate
      of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly
      statistically significant independent predictor of PSM (P < 0.001) and increased
      the predictive accuracy in multivariate models both before (2.0%) and after RP
      (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who
      contributed to 1293 cases, was removed from the analyses, the multivariate
      independent prediction and the gains in predictive accuracy related to adding SV,
      disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P
      = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that
      patients treated by surgeons with a very high volume can expect to have a
      significantly lower rate of PSM, after accounting for clinical and pathological
      case-mix differences. However, SV is not a predictor of PSM when analyses are
      restricted to intermediate- and low-volume surgeons.

PMID- 17034507
TI  - Androgen receptor mutations are associated with Gleason score in localized
      prostate cancer.
AB  - OBJECTIVE: To study human androgen receptor (hAR) mutations and their
      relationship to the clinical and pathological characteristics of patients with
      prostate cancer, as the mechanisms by which tumour cells escape androgen control
      and grow independently of hormone stimulation are unclear. PATIENTS AND METHODS:
      In all, 67 radical prostatectomy specimens were sequenced genomically (mean age
      of the patients, 64 years; median prostate-specific antigen level 15 ng/mL; 34%
      T1 and 66% T2). Of the 66 patients who had a valid follow-up, 28 (43%) had
      biochemical progression during the follow-up. RESULTS: There was mutation in the
      hAR in 11 patients (16%); nine types of different mutations were identified, only
      one of which was described previously in patients with prostate cancer. Patients
      with mutated hAR had statistically lower Gleason scores (P = 0.004) than had
      patients with native hAR. CONCLUSION: hAR mutations have a different effect on
      the disease course in patients with localized than in those with metastatic
      prostatic cancer.

PMID- 17034508
TI  - Prognostic significance of common preoperative laboratory variables in clear cell
      renal cell carcinoma.
AB  - OBJECTIVE: To investigate the prognostic significance of common preoperative
      laboratory variables evaluated before surgery for clear cell renal cell carcinoma
      (RCC). PATIENTS AND METHODS: We retrospectively analysed the records of 355
      patients who had surgery for clear cell RCC, assessing: clinical factors,
      including preoperative laboratory measurements, i.e. haemoglobin level, leukocyte
      count, platelet count, erythrocyte sedimentation rate (ESR), serum calcium,
      alkaline phosphatase (ALP), albumin, bilirubin, alanine aminotransferase,
      aspartate aminotransferase, and red blood cells in urine; and pathological
      factors, with the survival rates after surgery. RESULTS: The presence of
      metastasis, tumour stage and tumour size, with the ESR and ALP before surgery,
      were identified as significant prognostic factors for progression-free survival
      in a multivariate analysis. The same factors were significant independent factors
      for disease-specific survival, except for ESR and ALP, which were nearly
      statistically significant. When limited to non-metastatic tumours only, the
      multivariate analysis showed that ESR and ALP, with tumour stage, grade, size and
      necrosis, were independent prognostic factors for disease-specific survival.
      CONCLUSIONS: Along with traditionally accepted prognostic factors, these results
      suggest that common laboratory variables assessed before surgery, e.g. ESR and
      ALP, might also be useful in assessing the prognosis for patients with non
      metastatic clear cell RCC. Including various laboratory variables in prognostic
      algorithms for RCC should be considered after further validation in RCCs of
      various histological subtypes and stages.

PMID- 17034509
TI  - Hot and cold technologies for tissue ablation in urology.

PMID- 17034510
TI  - Is it possible to use urodynamic variables to predict upper urinary tract
      dilatation in children with neurogenic bladder-sphincter dysfunction?
AB  - OBJECTIVE: To investigate the possibility of using urodynamic variables to
      predict upper urinary tract dilatation (UUTD) in children with neurogenic bladder
      sphincter dysfunction (NBSD). PATIENTS AND METHODS: The study included 200
      children with NBSD, of whom 103 had UUTD and 97 did not; they were examined using
      routine urological, neurological and urodynamic methods. The group with UUTD was
      divided into three subgroups (group 1-3, from mild to severe hydronephrosis). A
      urodynamic risk score (URS) was calculated, including a detrusor leak-point
      pressure (DLPP) of >40 cmH2O, a bladder compliance (BC) of <9 mL/cmH2O and
      evidence of acontractile detrusor (ACD). RESULTS: The postvoid residual urine
      volume (PVR), DLPP, incidences of ACD and DLPP of >40 cmH2O were greater and the
      BC significantly less in groups 1-3 than in the control group. Moreover, the BC
      decreased, while the PVR, DLPP and the incidence of DLPP of >40 cmH2O were
      significantly higher in group 3 than in group 2. The relative safe cystometric
      capacity of groups 2 and 3 were lower, respectively, than that of the control and
      group 1, and the relative unsafe cystometric capacity (RUCC) and relative risk
      rate of cystometric capacity (RRRCC) were significantly greater with the severity
      of UUTD. The maximum detrusor pressure on voiding or at maximum flow rate, and
      the Abrams-Griffiths number for voluntary contractile bladders, of the UUTD group
      were significantly higher than those of the control group. There was a positive
      correlation between URS and UUTD. CONCLUSIONS: The selective use of urodynamic
      variables might be valuable for predicting the risk of UUTD in children with
      NBSD. Decreased BC, and increased DLPP and ACD are the main urodynamic risk
      factors, and they reciprocally increase the occurrence and grades of UUTD. The
      grades of UUTD are compatible with increases in RUCC, RRRCC and URS.

PMID- 17034512
TI  - Bleomycin and the skin.
AB  - Bleomycin is frequently used as a chemotherapeutic agent to treat various kinds
      of malignancy. However, the cytotoxic effects of bleomycin cause a number of
      adverse responses, in particular in the lung and the skin. Bleomycin is used by
      dermatologists as a treatment for various skin cancers, recalcitrant warts,
      keloid and hypertrophic scars. This article discusses the use of bleomycin for
      various skin disorders, as well as the risk factors and cutaneous side-effects
      resulting from its use.

PMID- 17034513
TI  - The role of neuropeptides in psoriasis.
AB  - The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic
      inflammation is probably involved. This involvement is suggested by a number of
      clinical and histological observations. Reports about the distribution of
      cutaneous nerves and the quantification of nerve growth factor and neuropeptides,
      including calcitonin gene-related peptide and vasoactive intestinal peptide, in
      lesional and nonlesional psoriatic skin suggest that sensory neuropeptides
      contribute to the development of psoriasis. This review summarizes what is known
      about the role of neurogenic markers in psoriasis.

PMID- 17034514
TI  - Changes in the number of Merkel cells with the hair cycle in hair discs on rat
      back skin.
AB  - BACKGROUND: Hair discs are known to contain a large number of Merkel cells and
      are ideal for investigating Merkel cell biology. Hair follicles, which are
      important elements of hair discs, undergo unique cyclical morphological and
      biological changes. OBJECTIVES: To define the relationships between the number
      and the morphology of Merkel cells within the hair disc in association with the
      hair cycle on rat back skin. METHODS: Merkel cells in hair discs were observed
      three-dimensionally using immunohistochemistry. Epidermal sheets were incubated
      with monoclonal murine antibody to CK20. As a result, Merkel cells in hair discs
      were clearly demonstrated as whole shapes and were counted under a light
      microscope. RESULTS: Merkel cells in hair discs increased during the early to
      middle phase of anagen and decreased during the middle phase of anagen to catagen
      and telogen in perinatal and postnatal rat back skin. We observed the
      morphological variation of Merkel cells in hair discs of rat back skin, and
      consequently divided them into two subtypes at the light microscopic level: the
      oval type and the dendritic type. The number of oval-type Merkel cells was not
      markedly affected by the hair cycle. In contrast, the number of dendritic-type
      Merkel cells markedly changed with the hair cycle. CONCLUSIONS: This difference
      of the hair cycle dependency between oval and dendritic-type Merkel cells
      suggests some functional differences, such as a secretory function, related to
      the hair cycle.

PMID- 17034515
TI  - Sebum output as a factor contributing to the size of facial pores.
AB  - BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged
      pilosebaceous pores. Such factors include sex, genetic predisposition, ageing,
      chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea.
      This study was an attempt to determine the factors related to enlarged pores.
      OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal
      factors and severity of acne with pore size. METHODS: A prospective, randomized,
      controlled study was designed. A total of 60 volunteers, 30 males and 30 females,
      were recruited for this study. Magnified images of pores were taken using a
      dermoscopic video camera and measured using an image analysis program. The sebum
      output level was measured with a Sebumeter. RESULTS: Using multiple linear
      regression analysis, increased pore size was significantly associated with
      increased sebum output level, sex and age. Among the variables, sebum output
      level correlated most with the pore size followed by male sex. In comparing male
      and female participants, males had higher correlation between the sebum output
      level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional
      factors seem to influence pore size in females. Pore size was significantly
      increased during the ovulation phase (P = 0.008), but severity of acne was not
      significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are
      associated with increased sebum output level, age and male sex. In female
      patients, additional hormonal factors, such as those of the menstrual cycle,
      affect the pore size.

PMID- 17034516
TI  - Comedolytic effect of topically applied active vitamin D3 analogue on
      pseudocomedones in the rhino mouse.
AB  - BACKGROUND: Retinoids and active vitamin D(3) analogues regulate the
      proliferation and differentiation of keratinocytes and are effective in the
      treatment of psoriasis. Retinoids are known to be effective against acne vulgaris
      through comedolysis. However, the comedolytic effect of active vitamin D(3)
      analogues has not been reported. OBJECTIVES: To investigate whether maxacalcitol,
      one of the active vitamin D(3) analogues, has a comedolytic effect by using
      spontaneously comedogenic rhino mice. METHODS: Rhino mice were treated topically
      with tretinoin and maxacalcitol once daily for 2 and 4 weeks, respectively. The
      dermal side of the epidermal sheet was observed to determine the size of the
      utricle. Haematoxylin and eosin-stained vertical sections were used to measure
      utricle diameter and density and to evaluate histological changes. RESULTS:
      Maxacalcitol (25 microg g(-1)) and tretinoin (0.1%) significantly decreased the
      size and the diameter of the utricle after 1 week of treatment. However,
      maxacalcitol did not affect the density while tretinoin did have an effect.
      Histopathologically, maxacalcitol and tretinoin markedly induced epidermal
      hyperplasia accompanied by a minor accumulation of inflammatory cells in the
      dermis, with and without hypercornification, respectively. CONCLUSIONS: These
      results indicate that maxacalcitol has a prominent effect on comedolysis and that
      its mechanism of action may be different from that of retinoids.

PMID- 17034517
TI  - Isolation and characterization of outer root sheath melanocytes of human hair
      follicles.
AB  - BACKGROUND: Outer root sheath melanocytes (ORSM) are not yet routinely cultured
      and their biology is not known in detail because of their relatively low numbers
      in the hair follicle and their limited proliferative capacity in in vitro culture
      in routine media. OBJECTIVES: To develop a method for culturing ORSM more easily
      and to investigate the length of telomeres and antigenic characteristics of ORSM
      compared with epidermal melanocytes (EM). METHODS: Hair follicles were obtained
      from three Korean individuals during hair transplantation surgery. Single-cell
      suspensions of the outer root sheath were made and cultured in melanocyte growth
      medium with stem cell factor. After 21 days, second-passage outer root sheath
      keratinocytes (ORSK) (2 x 10(4) mL(-1) MGM) were added into the culture plates.
      We studied the proliferation pattern, morphological and antigenic characteristics
      of ORSM for each passage of cultured cells, and observed ORSM telomere length.
      RESULTS: We established an ORSM culture method using ORSK. Two morphologically
      different ORSM types were obtained in the primary cultures. At the end of primary
      culture, ORSM appeared as whitish-cream pellets. The proliferation pattern of
      ORSM showed a sigmoidal shape, the accumulated numbers of population doublings
      showed a plateau after approximately 5 months, and senescence occurred at
      approximately 33 +/- 5 accumulated population doublings. The length of ORSM
      telomeres continued to shorten as the cells proliferated. In contrast, EM showed
      a marked proliferation from the early proliferation period which formed a plateau
      pattern towards the later period, and the number of accumulated population
      doublings was estimated to be 18 +/- 5 after 2 months. ORSM in the primary
      culture reacted variably with l-dihydroxyphenylalanine (DOPA): some cells were
      DOPA negative, some DOPA positive. There were some different antigenic
      expressions of microphthalmia-associated transcription factor (MITF) showing
      cytoplasmic expression in ORSM and nuclear expression in EM. By nuclear
      extraction and Western blotting, we showed that MITF expression of ORSM was
      marked in the cytoplasm and minimal in the nucleus. Antigenic expression of MITF
      and Bcl-2 gradually decreased with increasing passage number, whereas tyrosinase
      related protein-1 expression did not change. CONCLUSIONS: Culture of ORSM
      requires ORSK or ORSK-related factors; ORSM have greater proliferation potential
      and show different MITF antigenic expression compared with EM; and the length of
      ORSM telomeres shortens with repeated proliferation.

PMID- 17034518
TI  - Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in
      various skin tumours.
AB  - BACKGROUND: Various types of external stress cause the skin and central
      neuroendocrine system to express corticotropin-releasing hormone (CRH)
      proopiomelanocortin (POMC) axis-related hormones. However, the precise role of
      the CRH-POMC axis-related hormones in various skin tumours is unclear.
      OBJECTIVES: This study examined expression patterns of the CRH-POMC axis-related
      hormones in skin tumours. METHODS: The production of CRH, adrenocorticotropic
      hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various
      tumour cell lines including HaCaT and primary keratinocytes was examined using an
      enzyme-linked immunosorbent assay. Immunohistochemical analysis of the skin
      tumours was also performed. RESULTS: CRH, ACTH and alpha-MSH were strongly
      expressed in malignant skin tumour cell lines such as G-361 and DX-3 (both
      malignant melanoma, MM). However, normal and haematological malignancy cell lines
      did not express the CRH-POMC axis-related hormones. Immunohistochemical analysis
      of the skin tumours showed that MM (80%), squamous cell carcinoma (SCC, 70%) and
      basal cell carcinoma (BCC, 10%) had strong immunoreactivity (++/+++) for CRH.
      Strong ACTH and alpha-MSH expression was observed in MM (70% and 50%,
      respectively), SCC (80% and 60%, respectively) and BCC (70% and 50%,
      respectively). CONCLUSIONS: We report that an increase in the level of the CRH
      POMC axis-related hormones is associated with malignant skin tumours such as MM.
      These results highlight the importance of the CRH-POMC axis-related hormones in
      the malignant tendency of skin tumours.

PMID- 17034519
TI  - Specialist dermatology clinics for organ transplant recipients significantly
      improve compliance with photoprotection and levels of skin cancer awareness.
AB  - BACKGROUND: Organ transplant recipients (OTRs) have 100-fold increased risk of
      developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation
      is the main risk factor and there is evidence that lack of dermatological
      surveillance may be responsible for poor levels of knowledge and photoprotection
      among OTRs. OBJECTIVES: This study evaluated whether routine consultation in a
      specialist OTR dermatology clinic improves understanding of skin cancer risk and
      compliance with photoprotection measures. METHODS: A cross-sectional
      questionnaire-based study was performed in a specialist OTR dermatology clinic at
      Bart's and the London NHS Trust, London, U.K. The subjects were 399 white-skinned
      patients under surveillance in a renal transplant clinic, who were sent a postal
      questionnaire from the renal transplant clinic. The main outcome measures were
      responses to the questionnaire regarding photoprotective practices and skin
      cancer risk awareness. RESULTS: Two hundred and ninety-two of 399 (73%)
      responded, of whom 89% had previously attended the specialist dermatology clinic.
      Ninety-six per cent recalled receiving photoprotection advice at least once (85%
      from dermatologists); 92% reported use of sunscreen; 88% specifically dressed to
      photoprotect themselves; 96% directly avoided sun exposure during summer; 68%
      were aware that an increased risk of skin cancer was the reason that extra
      photoprotective measures were important after a transplant. Photoprotective
      measures and level of skin cancer awareness were significantly lower in those
      responders who had never attended the specialist clinic. No obvious bias was
      identified among nonresponders. CONCLUSIONS: Skin cancer awareness and compliance
      with photoprotective measures in our patient population is generally greater than
      previously reported, suggesting that delivery of educational messages regarding
      skin cancer may be improved if provided in a specialist dermatological setting.

PMID- 17034520
TI  - Follicular miniaturization in female pattern hair loss: clinicopathological
      correlations.
AB  - BACKGROUND: The pathology of female pattern hair loss (FPHL) is characterized by
      an increase in the proportion of vellus follicles, manifest as a low
      terminal/vellus ratio. This is conventionally thought to be due to a progressive
      miniaturization of terminal hair follicles. There is also a prolongation of the
      latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL
      and follicles in kenogen may be difficult to classify histologically. Therefore,
      a low terminal/vellus ratio could be due to a preferential increase in the number
      of terminal follicles in kenogen rather than to a true increase in the number of
      vellus follicles. OBJECTIVES: To establish whether there is an increase in the
      absolute number of vellus follicles during the progression of FPHL, indicating a
      process of follicular miniaturization. METHODS: We studied 42 women complaining
      of hair loss. The severity of the hair loss was graded clinically on a five-point
      scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch
      biopsies were taken from the frontal scalp of each patient, sectioned
      horizontally and stained with haematoxylin and eosin. Two levels were studied on
      each biopsy: through the mid-infundibular region and through the mid-isthmus. The
      following were counted: total follicles, terminal follicles, vellus follicles,
      anagen and telogen/catagen follicles. The results from the three biopsies from
      each subject were averaged and statistical evaluations performed on the mean
      values. RESULTS: There was a progressive decline in mean total follicle count
      with increasing grade of hair loss (grade 1, 317 cm(-2); grade 5, 243 cm(-2)) and
      a more pronounced reduction in terminal follicle counts (grade 1, 263 cm(-2);
      grade 5, 96 cm(-2)). The absolute number of vellus follicles increased from 33
      cm(-2) (grade 1) to 71 cm(-2) (grade 4), declining to 51 cm(-2) at grade 5. The
      terminal/vellus ratio fell from 12.8 (grade 1) to 2.3 (grade 4) and remained at
      this level thereafter. The proportion of follicles in telogen increased from
      13.7% (grade 1) to 31.4% (grade 5). CONCLUSIONS: Our results show that there is
      an increase in vellus follicle numbers with increasing severity of hair loss in
      women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is
      possible that there is also an increase in the number of follicles in a latent
      stage of telogen but this was difficult to assess from our data. The fall in
      total follicle counts with stabilizing of the terminal/vellus ratio in severe
      hair loss suggests that miniaturization does not stop with a vellus follicle but
      progresses to follicular deletion.

PMID- 17034521
TI  - Cytokine alterations in lichen sclerosus: an immunohistochemical study.
AB  - BACKGROUND: Although the histology of lichen sclerosus is characteristic, the
      precise nature of the inflammatory changes and the signals provoking them is
      uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus
      more accurately by studying cytokine changes. METHODS: An immunohistochemical
      study of 12 specimens of genital lichen sclerosus and one specimen of
      extragenital lichen sclerosus was undertaken using monoclonal antibodies to
      interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1
      (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal
      vulva obtained during gynaecological procedures, three specimens of normal skin,
      adjacent uninvolved thigh from three of the patients with lichen sclerosus, five
      specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and
      two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens
      demonstrated slightly increased staining for IFN-gamma within the epidermis
      compared with the normal vulva and nonvulval skin. There was increased dermal
      staining for IFN-gamma both within the pale zone of the upper dermis and within
      the inflammatory zone below this. We confirmed our previous demonstration that in
      lichen sclerosus HLA-DR immunostaining is increased in association with vascular
      endothelium, the inflammatory cell infiltrate and around the keratinocytes. The
      areas of the epidermis with the strongest immunostaining for HLA-DR generally
      also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens
      the zone of inflammation also demonstrated increased immunostaining for TNF
      alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of
      sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma
      receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased
      staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF
      alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the
      cytokine response in lichen sclerosus shares characteristics of the cytokine
      response in lichen planus and chronic wounds.

PMID- 17034522
TI  - Prospective aetiological study of diaper dermatitis in the elderly.
AB  - BACKGROUND: The different causes of diaper dermatitis (DD) in the elderly are not
      well known and the treatment is often empirical. OBJECTIVES: To determine the
      causes of DD in the elderly and to evaluate the efficacy of antifungal treatments
      in this indication. METHODS: Consecutive patients presenting with DD were
      included. Clinical evaluation, skin swabs for bacterial and mycological cultures,
      patch testing and skin biopsy were performed at inclusion. This was followed by 1
      month of topical antifungal cream and, if needed, by oral fluconazole for the
      second month. RESULTS: Forty-six patients were included (mean age 85 years).
      Causes of DD were established for 38 patients: 24 had candidiasis (63%), six
      irritant dermatitis (16%), four eczema (11%) and four psoriasis (11%). After 2
      months of treatment, 27 of 37 (73%) patients were cured and five of 37 were
      improved. CONCLUSIONS: Mycoses and irritant dermatitis are the main causes of DD
      in the elderly, and emollient skin care and topical antifungal treatment can be
      considered a first-line therapy for this indication.

PMID- 17034523
TI  - Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the
      lower leg: a series with community follow-up.
AB  - BACKGROUND: Cellulitis of the lower leg is a common problem with considerable
      morbidity. Risk factors are well identified but the relationship between
      consequences of cellulitis and further episodes is less well understood.
      OBJECTIVES: To review risk factors, treatment and complications in patients with
      lower leg cellulitis, to determine the frequency of long-term complications and
      of further episodes, and any relationship between them, and to consider the
      likely impact of preventive strategies based on these results. METHODS: Patients
      with ascending, presumed streptococcal, cellulitis of the lower leg were
      identified retrospectively from hospital coding. Hospital records, together with
      questionnaires to both general practitioners and patients, were used to record
      subsequent complications and identifiable risk factors for further episodes.
      RESULTS: Of 171 patients, 81 (47%) had recurrent episodes and 79 (46%) had
      chronic oedema. The concurrence of these two factors was strongly correlated (P <
      0.0002). Based on 143 completed questionnaires, oedema was apparently due to or
      persistently asymmetrical after the cellulitic episode in 52 (37%), and 19 (13%)
      had ulceration attributed to, rather than causing, cellulitis. Of those with
      three or more episodes, half did not lead to hospital admission. Toeweb
      maceration was reported in only 15% of questionnaires. Use of antibiotic
      treatment for more than 28 days was associated with a reduced risk of leg
      ulceration or of prolonged oedema compared with shorter courses, but neither
      difference was statistically significant. CONCLUSIONS: This study demonstrates
      that the true frequency of postcellulitic oedema, as well as that of further
      episodes, is probably underestimated. Furthermore, there is a strong association
      between these factors, each of which is both a risk factor for, and a consequence
      of, each other, and for which intervention (reduction of oedema or more prolonged
      antibiotic therapy) may reduce the risk of recurrent infection. By contrast, self
      reporting of toeweb maceration is low, so attempts to reduce the risk of
      recurrent cellulitis by treatment of tinea pedis or bacterial intertrigo may
      fail.

PMID- 17034524
TI  - Dermoscopy of facial nonpigmented actinic keratosis.
AB  - BACKGROUND: The accuracy of clinical diagnosis of nonpigmented, facial actinic
      keratosis (AK) is often suboptimal, even for experienced clinicians. OBJECTIVES:
      To investigate the dermoscopic features of nonpigmented AK located on the
      head/neck that may assist the clinical diagnosis. METHODS: Forty-one nonpigmented
      AKs on facial sites were examined by dermoscopy for any consistent underlying
      features. Lesions were gathered from skin cancer centres in Australia, Austria,
      Italy and the U.S.A. All cases were diagnosed histopathologically. RESULTS: Four
      essential dermoscopic features were observed in facial AK: (i) erythema,
      revealing a marked pink-to-red 'pseudonetwork' surrounding the hair follicles
      (95%); (ii) white-to-yellow surface scale (85%); (iii) fine, linear-wavy vessels
      surrounding the hair follicles (81%); and (vi) hair follicle openings filled with
      yellowish keratotic plugs (66%) and/or surrounded by a white halo (100%). These
      features combined, in 95% of cases, to produce a peculiar 'strawberry'
      appearance. CONCLUSIONS: A dermoscopic model of 'strawberry' pattern is
      presented, which may prove helpful in the in vivo diagnosis of nonpigmented,
      facial AK. A limitation of this study is the lack of testing of the specificity
      of the described dermoscopic criteria in differentiating nonpigmented AKs from
      other nonpigmented skin lesions at this site.

PMID- 17034525
TI  - Pruritus as a leading symptom: clinical characteristics and quality of life in
      German and Ugandan patients.
AB  - BACKGROUND: Pruritus is the most frequent and distressing symptom associated with
      dermatoses and various internal and neurological diseases. OBJECTIVES: To
      investigate two different populations of patients with pruritus, one in Germany
      and one in Uganda, with a particular focus on clinical characteristics, aetiology
      and quality of life. METHODS: We investigated by questionnaire 132 patients (59
      men, 73 women, mean age 54.5 years) who were referred to the Department of
      Dermatology at the University Hospital of Magdeburg, Germany, with the diagnosis
      of pruritus as a leading symptom. The questionnaire was also applied in 84
      patients who consulted the Dermatology Clinic at Mbarara, Uganda for pruritus.
      The questions referred to personal data and disease history of the individual,
      history and present occurrence of concomitant diseases, present and past therapy,
      quality, frequency and triggers of itching and scratching, other disorders and
      complaints, quality of life and impact on work and disability. RESULTS: Seventy
      five (57%) of the German patients had pruritus due to dermatoses, 47 patients
      (36%) had pruritus due to a systemic disease and in 10 patients (8%) pruritus was
      of unknown origin. Most had a history of pruritus of several months up to years.
      Pruritus associated with dermatoses mostly affected the whole body and was
      permanent with an undulatory character. Affective reactions such as aggression
      and depression occurred more frequently in dermatological patients compared with
      those with systemic pruritus. The former group felt that pruritus had a greater
      impact on their lives. Almost all Ugandan patients had pruritus due to dermatoses
      except for three patients with pruritus of unknown origin. Eczema and prurigo
      were the most frequently observed dermatoses in both German and Ugandan patients.
      Patients with pruritus in both populations showed an impaired quality of life.
      There was no pronounced difference between the populations with regard to
      feelings of depression and suicidal thoughts. CONCLUSIONS: A great deal of
      helpful information in this complex group of patients can be obtained using this
      questionnaire. Pruritus has a major impact on quality of life and especially
      impairs those patients with pruritus associated with dermatoses and pruritus of
      unknown origin.

PMID- 17034526
TI  - Striae gravidarum in primiparae.
AB  - BACKGROUND: Striae distensae are widely known to occur in pregnancy and
      aesthetically they can be a cause of great concern for many women. Various
      factors have been reported to be associated with the development of striae but
      the results are conflicting. OBJECTIVES: To observe the prevalence of striae
      gravidarum in primiparae and identify independent associated risk factors.
      METHODS: An observational analysis of 324 primiparae was conducted within 48 h of
      delivery. Data was collected in the form of a questionnaire and physical
      examination. Seventy-two primiparae participated in a pilot study in 1999 and the
      remaining were assessed over a 4-month period in 2000. Seventeen variables were
      recorded, and striae graded according to quantity and severity. Fifteen
      primiparae were excluded prior to analysis. RESULTS: Fifty-two per cent (161 of
      309) of primiparous white women had striae of which 12% (20 of 161) were
      classified as severe. The most significant risk factor was low maternal age (P <
      0.0001). Twenty per cent (14 of 71) of teenagers had severe striae, a finding not
      seen in women over 30 years of age. Other significant risk factors included
      maternal body mass index greater than 26 (P = 0.0003), maternal weight gain of
      more than 15 kg (P = 0.0121) and high neonatal birth weight (P = 0.0135).
      CONCLUSIONS: Logistic regression analysis demonstrated that maternal age, body
      mass index, weight gain and neonatal birth weight were independently associated
      with the occurrence of striae. It appears that the group at highest risk of
      developing severe striae are teenagers. This finding is important and may provide
      impetus to explore the pathomechanisms of striae.

PMID- 17034527
TI  - Cutaneous innervation before and after one treatment period of acupuncture.
AB  - BACKGROUND: The effect of acupuncture on nociceptive pain is well documented, but
      effects on nociceptive itch have been contradictory. OBJECTIVES: To evaluate
      possible effects of acupuncture on the occurrence, distribution and function of
      sensory nerve fibres in human skin. METHODS: Ten subjects were treated by
      inserting 10 acupuncture needles subcutaneously at the upper lateral aspect of
      one buttock. The subjects were recruited from an acupuncture clinic and were
      undergoing specific acupuncture treatment for their disorders. The needles were
      stimulated (rotated to and fro) twice during the twice-weekly 25-min sessions
      over 5 weeks. Skin biopsies, diameter 3 mm, were taken before and 3-6 days after
      local acupuncture. Antibodies to the pan-neuronal marker protein gene product 9.5
      (PGP 9.5), calcitonin gene-related peptide (CGRP), vanilloid receptor 1 (VR1) and
      mu- and delta-opioid receptors were employed to study sensory unmyelinated nerve
      fibres that transmit nociceptive pain and itch. A histamine prick test using
      planimetry was used to record experimental itch after acupuncture on the treated
      area and on the corresponding control skin, and a visual analogue scale was used
      to evaluate itch. RESULTS: The mean +/- SEM number of CGRP-immunoreactive nerve
      fibres per biopsy section was reduced from 36.0 +/- 3.3 to 21.3 +/- 4.0 (P =
      0.05) after the treatment. PGP 9.5-immunoreactive nerve fibres were found both in
      the epidermis and in the subpapillary dermis. The mean +/- SEM total number of
      PGP 9.5-immunoreactive nerve fibres decreased from 249.8 +/- 16.7 to 211.8 +/-
      12.0 (P = 0.03). The PGP 9.5-immunoreactive nerve fibres occurring in the dermis
      appeared more fragmented after the acupuncture compared with pretreatment. VR1
      immunoreactivity was found both in the free nerve fibres and in kite-like
      formations, possibly mast cells, throughout the dermis, sometimes occurring
      around hair follicles. The mean +/- SEM number of VR1-immunoreactive elements was
      not significantly influenced by acupuncture, at 33.5 +/- 4.6 vs. 43.0 +/- 4.4 (P
      = 0.09). No immunoreactivity was found in the skin against mu- and delta-opioid
      receptors with the antibodies used in this study. Neither histamine-induced itch
      nor cutaneous responses were influenced by acupuncture. CONCLUSIONS: The present
      data indicate an effect of acupuncture on neuropathic itch but not histamine
      mediated itch. Our findings support the opinion that the pain-relieving effects
      of acupuncture partly depend on its effect on the peripheral innervation.

PMID- 17034528
TI  - Characteristics of cutaneous cytomegalovirus infection in non-acquired immune
      deficiency syndrome, immunocompromised patients.
AB  - BACKGROUND: Although cytomegalovirus (CMV) disease is a severe complication among
      immunocompromised patients, its cutaneous features have not been frequently
      reported. As herpes simple virus (HSV) infection commonly develops in CMV skin
      lesions, a study is needed on the pathogenetic role of CMV in cutaneous lesion
      formation. OBJECTIVES: The purpose of this study is to characterize the clinical
      and histopathological features of cutaneous CMV infection and to determine
      whether CMV plays a true pathogenetic role in cutaneous lesions, or if it is just
      an innocent bystander during HSV infection among non-AIDS (acquired immune
      deficiency syndrome), immunocompromised patients. PATIENTS AND METHODS: A total
      of nine human immunodeficiency virus-negative patients diagnosed with cutaneous
      CMV infection from July 1999 to February 2005 at Samsung Medical Center were
      analysed in terms of their clinical and histopathological characteristics. In
      addition, we examined for the co-presence of HSV by performing
      immunohistochemical analysis and polymerase chain reaction. RESULTS: All the
      patients were immunocompromised; five had haematological diseases and four were
      organ transplant recipients. The clinical and histopathological features were
      similar to those of previous studies of patients with AIDS. Multiple anogenital
      ulcerations were the most frequent cutaneous presentation (66.7%). Most
      cytopathic changes were found in the dermis, particularly within the vascular
      endothelial cells (77.8%) and macrophages (66.7%). However, the association of
      CMV with concurrent HSV infection was even lower than that seen in patients with
      AIDS. Only one patient revealed a co-existing cutaneous HSV infection.
      CONCLUSIONS: In non-AIDS individuals, the cutaneous lesions from CMV infection
      showed similar clinical and histopathological features to those of patients with
      AIDS. However, skin lesions may not be highly associated with HSV, and CMV does
      seem to contribute to lesion development as a cutaneous manifestation among the
      CMV infected, non-AIDS, immunocompromised patients.

PMID- 17034529
TI  - Elevated serum IgA anticardiolipin antibody levels in adult Henoch-Schonlein
      purpura.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis
      characterized by palpable purpura on the lower extremities and IgA-dominant
      immune complex deposition within the wall and lumen of dermal vessels in the
      lesions. This disorder is associated, to varying degrees, with joint,
      gastrointestinal and renal involvement. Antiphospholipid antibodies, including
      anticardiolipin antibodies (aCL Abs), are a heterogeneous group of circulating
      autoantibodies found in patients with autoimmune and infectious diseases.
      OBJECTIVES: To investigate the possible role of aCL Abs in adult HSP, we measured
      levels of serum IgA, C-reactive protein (CRP), aCL Abs of the IgG, IgM and IgA
      isotypes and anti-beta(2)-glycoprotein I (beta(2)GPI)-dependent aCL Abs in adult
      patients with HSP. We evaluated the correlation between these biological
      parameters and the clinical manifestations. METHODS: Adult patients with HSP with
      an initial cutaneous manifestation of palpable purpura on their lower extremities
      seen between 2001 and 2005 in our department were retrospectively reviewed.
      Patients with known connective tissue diseases were not included in the study.
      Histological examination of all patient skin biopsy specimens revealed
      leucocytoclastic vasculitis in the upper and mid-dermis. Direct
      immunofluorescence analysis showed prominent deposits of IgA in the capillary
      walls of all patients. Blood samples were taken at the time that the patient
      presented. Serum levels of aCL Abs and anti-beta(2)GPI-dependent aCL Abs were
      measured by enzyme-linked immunosorbent assay. RESULTS: Twenty adult patients
      with HSP (12 men and eight women), mean age 62.2 years (range 23-81) were
      enrolled. IgA aCL Abs were found in 15 of the 20 patients (75%). All were
      negative for IgG aCL Abs, IgM aCL Abs and anti-beta(2)GPI-dependent aCL Abs. The
      elevation of serum IgA aCL Abs in the 15 patients showed a significant
      correlation with serum IgA and CRP levels (r(s) = 0.91, P = 0.0007; r(s) = 0.80,
      P = 0.0026, respectively). Levels of serum IgA aCL Abs were also significantly
      associated with arthralgia (P = 0.022) and proteinuria according to urinalysis (P
      = 0.013). CONCLUSIONS: Serum levels of IgA aCL Abs are elevated in the initial
      active stage of adult HSP, suggesting that serum IgA aCL Abs may play some role
      in the onset of adult HSP. We believe that serum IgA aCL Abs might be an
      indicator of adult HSP activity.

PMID- 17034530
TI  - Dysplastic naevi with moderate to severe histological dysplasia: a risk factor
      for melanoma.
AB  - BACKGROUND: The risk of malignant melanoma associated with histologically
      dysplastic naevi (HDN) has not been defined. While clinically atypical naevi
      appear to confer an independent risk of melanoma, no study has evaluated the
      extent to which HDN are predictive of melanoma. OBJECTIVES: To estimate the risk
      of melanoma associated with HDN. Secondarily, the risk associated with number of
      naevi and large naevi is estimated. METHODS: We enrolled 80 patients with newly
      diagnosed melanoma along with 80 spousal controls. After obtaining information on
      melanoma risk factors and performing a complete cutaneous examination, the most
      clinically atypical naevus was biopsied in both cases and controls. Histological
      dysplasia was then assessed independently by 13 dermatopathologists (0, no
      dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The
      dermatopathologists were blinded as to whether the naevi were from melanoma
      subjects or controls. Multivariate analyses were performed to determine if there
      was an independent association between the degree of histological dysplasia in
      naevi and a personal history of melanoma. RESULTS: In persons with naevi
      receiving an average score of > 1 (i.e. naevi considered to have greater than
      mild histological dysplasia), there was an increased risk of melanoma [odds ratio
      (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after
      adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few
      dermatopathologists reliably graded naevi of subjects with melanoma as being more
      dysplastic than naevi of control subjects. Among the entire group, the
      interobserver reliability associated with grading histological dysplasia in naevi
      was poor (weighted kappa 0.28). CONCLUSIONS: HDN do appear to confer an
      independent risk of melanoma. However, this result may add more to our biological
      understanding of melanoma risk than to clinical assessment of risk, because HDN
      assessed by a single pathologist generally cannot be used to assess risk of
      melanoma. Future studies should be directed at establishing reproducible,
      predictive criteria for grading naevi.

PMID- 17034531
TI  - Prevalence of vulval lichen planus in a cohort of women with oral lichen planus:
      an interdisciplinary study.
AB  - BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that
      frequently involves the oral and genital mucosae. Patients with LP affecting
      these sites are often seen by oral medicine specialists or gynaecologists who
      work in isolation and depend heavily on histopathologists to help them in
      confirming the diagnosis. There are few studies in the literature combining the
      experiences of these specialists who share the care of patients with both oral
      and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a
      cohort of patients with histologically confirmed oral LP (OLP). METHODS: The
      study group consisted of 42 women histologically diagnosed with OLP. The mean age
      was 60.5 years (range 27-81). They underwent genital examination, colposcopy and
      vulvoscopy. For the histological confirmation of clinical VLP biopsies were
      performed whenever a clinical lesion was found. Oral and genital biopsy specimens
      were processed through histological and immunohistochemical staining.
      Histological diagnoses of LP were made according to the modified World Health
      Organization histopathological criteria proposed by van der Meij and van der Waal
      for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence,
      but without the histological confirmation of OLP and VLP, were excluded from the
      study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were
      obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who
      underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of
      the 12 patients free of symptoms such as itching, burning and dyspareunia, but
      with clinical vulval lesions, 11 (92%) had histological confirmation of VLP.
      Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS:
      This study showed a 57% prevalence of VLP in selected patients with OLP. The high
      prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed
      the usefulness of this careful integrated approach.

PMID- 17034532
TI  - Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent
      inactivation of the RB1/p16 and p53 pathways.
AB  - BACKGROUND: Aberrant methylation of CpG islands in the promoter regions of cancer
      related genes has been demonstrated in many human tumours. However, the
      methylation profile of these regions in cutaneous squamous cell carcinomas (SCCs)
      has not been well studied. OBJECTIVES: To examine epigenetic abnormalities of a
      wide range of cancer-related genes in SCCs. METHODS: We investigated the
      methylation status of 11 candidate cancer-related genes (CDH1, p16(INK4a),
      p14(ARF), DAPK1, MGMT, RB1, RASSF1, p15(INK4b), PTEN, PRDM2 and p53) in 20 cases
      of SCC by methylation-specific polymerase chain reaction, and comparatively
      examined the protein production of E-cadherin (CDH1), p16, RB1, p14, BMI1 and
      cyclin A by immunohistochemical analysis. RESULTS: The frequency of cancer
      related gene methylation in SCCs was: CDH1 (95%), p16 (20%), p14 (15%), DAPK1
      (15%), MGMT (15%), RB1 (5%), RASSF1 (5%), p15 (0%), PTEN (0%), PRDM2 (0%) and p53
      (0%). Almost all cases with hypermethylation of CDH1, p16, RB1 and p14 showed no
      obvious production of each protein, suggesting that promoter hypermethylation of
      these genes contributes to the loss of protein production. The results of
      methylation analysis, in combination with the results of our previous mutation
      analysis of CDKN2A locus and p53, revealed that 70% of SCCs have alterations in
      the RB1/p16 or p53 pathway. CONCLUSIONS: Our findings indicate that the promoter
      hypermethylation of cancer-related genes, especially CDH1, is frequently shown in
      SCCs, and dysregulation of the RB1/p16 and/or p53 pathway through either genetic
      or epigenetic mechanisms, except for epigenetic abnormalities of p53 itself,
      should contribute to the carcinogenesis of SCCs.

PMID- 17034533
TI  - Poor agreement between self-reported and dermatologists' diagnoses for five
      common dermatoses.
AB  - BACKGROUND: Few epidemiological studies assessing the prevalence of chronic
      dermatosis are available in France and most of these studies have used biased
      samples drawn from specific subpopulations. As several recent studies have
      mentioned that self-reported diagnosis either underestimates or overestimates
      disease prevalence, the validity of such data is questionable. OBJECTIVES: To
      evaluate the agreement between self-reported and dermatologists' diagnoses for
      five chronic dermatoses: acne, eczema, fungal infection, psoriasis and
      seborrhoeic dermatitis, and to analyse the factors associated with patients'
      diagnosis knowledge. PATIENTS/METHODS: A cross-sectional study was conducted on
      the national day of skin tumour screening in April 2003. A self-administered
      questionnaire was completed by patients and a standard form was completed by
      dermatologists after clinical examination. A total of 4,622 adults were examined
      by a dermatologist in 134 screening centres across France. The agreement between
      self-reported and dermatologists' diagnoses was analysed using the kappa index.
      Characteristics of patients who were aware of their diagnosis were compared with
      those of patients who were not, by using multivariate logistic regression models.
      RESULTS: The demographic characteristics of the sample differed from those of the
      French population. The self-reported prevalence was significantly lower than the
      actual prevalence for all diseases except eczema. Underestimations ranging from
      23% to 35% were observed in nearly all subgroups of our population. The agreement
      between self-reported and dermatologists' diagnoses was low to moderate. Many
      cases of chronic skin diseases were diagnosed in patients who did not report
      them. Diagnosis knowledge was poorer in those above 54 years of age and better
      for patients treated for the condition and those with impairment of social life.
      CONCLUSIONS: We observed a low agreement between self-reported and
      dermatologists' diagnoses for five chronic diseases. Self-reports underestimated
      the actual prevalence of four of five common diseases.

PMID- 17034534
TI  - Evaluation of methotrexate and corticosteroids for the treatment of localized
      scleroderma (morphoea) in children.
AB  - BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a
      benign self-limiting condition confined to the skin and subcutaneous tissue.
      However, the course of the disease is unpredictable and severe functional and
      cosmetic disability may result. Drug treatment with systemic corticosteroids in
      combination with methotrexate has been reported to be beneficial in LS, but data
      in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of
      systemic corticosteroids in combination with methotrexate in children with LS.
      METHODS: Treatment and outcome of 34 patients with LS were retrospectively
      analysed. Pulsed intravenous methylprednisolone was given, followed by oral
      prednisolone on a reducing regimen and maintenance treatment with methotrexate.
      We assessed treatment outcome clinically and by thermography and monitored
      adverse events. RESULTS: From the onset of treatment, the disease stopped
      progressing in 94% of the patients. All patients demonstrated significant
      clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of
      follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%)
      patients therapy was discontinued when the disease was considered to be inactive
      clinically; however, seven (44%) of the 16 developed a relapse, necessitating
      repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34
      patients had completely inactive disease. Observed adverse events were moderate
      and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest
      that systemic corticosteroids and methotrexate in combination are beneficial and
      well tolerated in the treatment of children with LS. Because of the risk of
      relapse after discontinuing therapy, long-term monitoring is mandatory.

PMID- 17034535
TI  - Multicentre, phase II trial on the safety and efficacy of topical tacrolimus
      ointment for the treatment of lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing
      significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory,
      with potent corticosteroids being the most effective therapy. OBJECTIVES: To
      conduct a multicentre, phase II trial to assess the safety and efficacy of
      tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up
      period of 18 months at 10 university and teaching hospitals in Germany and
      Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged
      between 5 and 85 years with long-standing, active lichen sclerosus (79 with
      anogenital and five with extragenital localization) were treated with topical
      tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the
      lesional area was performed. The primary endpoint was clearance of active lichen
      sclerosus. Secondary endpoints were time to optimal response, reduction of
      sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of
      active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment.
      Partial resolution was reached in 34% of patients. Maximal effects occurred
      between week 10 and 24 of therapy. Treatment led to a significant reduction of
      the total lesional area (P < 0.01) and to a significant decline in the total
      symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema,
      erosions and induration) showed significant improvement. No serious adverse
      events were observed. There were three (9%) recurrences during the follow-up
      period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for
      the treatment of long-standing active lichen sclerosus.

PMID- 17034536
TI  - Intraindividual, right-left comparison of topical methyl aminolaevulinate
      photodynamic therapy and cryotherapy in subjects with actinic keratoses: a
      multicentre, randomized controlled study.
AB  - BACKGROUND: Actinic keratosis (AK), the most common premalignant skin condition,
      can represent a management challenge. Treatment should not only be effective, but
      also well tolerated and allow for good cosmesis on typical sun-exposed highly
      visible body sites. OBJECTIVES: The primary objective was to compare the lesion
      response and subject preference for topical methyl aminolaevulinate (MAL)
      photodynamic therapy (PDT) vs. cryotherapy for the treatment of AK. METHODS: In
      this 24-week, multicentre, randomized, intraindividual (right-left) study,
      subjects received both one treatment session of MAL-PDT and a double freeze-thaw
      cryotherapy; the treatments were randomly allocated to either side of the
      face/scalp. Lesions with a noncomplete response were retreated after 12 weeks.
      The primary assessments were the subject's overall preference and lesion response
      at week 24. Secondary assessments included lesion response at week 12, cosmetic
      outcome, subject and investigator cosmetic outcome preference at week 24, and
      investigator overall preference at week 24. Skin discomfort and adverse events
      were also evaluated. RESULTS: In total, 119 subjects with 1,501 lesions were
      included in the study. At week 12, treatment with MAL-PDT resulted in a
      significantly larger rate of cured lesions relative to cryotherapy (percentage
      lesion reduction from baseline: 86.9% vs. 76.2%; P < 0.001). At week 24, both
      treatment groups showed a high rate of cured lesions (89.1% for MAL-PDT vs. 86.1%
      for cryotherapy; P = 0.20; 95% confidence interval: -1.62 to 7.67). Results for
      subject and investigator preferences as well as cosmetic outcome favoured MAL
      PDT. Both treatment regimens were safe and well tolerated. CONCLUSIONS: The
      present study shows that, when treated with both MAL-PDT and cryotherapy,
      subjects significantly prefer MAL-PDT treatment for AK. MAL-PDT is an attractive
      treatment option for AK, with comparable efficacy and superior cosmetic outcomes
      compared with double freeze-thaw cryotherapy.

PMID- 17034537
TI  - FK506 increases pigmentation and migration of human melanocytes.
AB  - BACKGROUND: Topical tacrolimus (FK506) is a potential therapeutic option for
      vitiligo management. Despite its clinical efficacy, the underlying mechanism of
      how topical tacrolimus induces repigmentation in vitiligo has scarcely been
      investigated. OBJECTIVES: To investigate the direct effects of FK506 on
      pigmentation and migration of human melanocytes. METHODS: Cell proliferation was
      measured using a Coulter counter. The effects on pigmentation were investigated
      by measuring melanin contents, tyrosinase activity and tyrosinase expression. To
      determine the effects of FK506 on cell migration, we performed scratch assays and
      Boyden chamber assays. RESULTS: FK506 treatment increased melanin contents,
      although there was an inhibitory effect on growth of melanocytes. The increase of
      pigmentation was due to the result of the stimulatory action of FK506 on
      tyrosinase activity and its expression, which eventually led to melanin
      biosynthesis. Furthermore, cell migration was enhanced by FK506 treatment.
      CONCLUSIONS: These findings provide in vitro evidence demonstrating direct
      effects of FK506 on pigmentation and melanocyte migration and may provide a
      possible mechanism for the effect of tacrolimus in vitiligo.

PMID- 17034538
TI  - Absent/reduced glucose transporter-1 protein expression in infantile subglottic
      haemangiomas.
AB  - BACKGROUND: Positive immunohistochemical staining for glucose transporter-1
      protein (GLUT1) is a characteristic of cutaneous infantile haemangiomas.
      OBJECTIVES: To examine GLUT1 expression in subglottic haemangiomas. METHODS:
      Review of clinical notes and biopsy tissue with immunostaining for GLUT1 in 14
      patients with subglottic haemangiomas. RESULTS: GLUT1 immunostaining was negative
      in 11 cases, and focally positive in three. No subglottic haemangiomas
      demonstrated the intense diffuse positive GLUT1 staining seen in cutaneous
      infantile haemangiomas. Five patients had cutaneous as well as subglottic
      haemangiomas, one of whom had a GLUT1-negative subglottic haemangioma and a GLUT1
      positive cutaneous haemangioma of the lip. CONCLUSIONS: Subglottic haemangiomas
      appear immunohistochemically different from cutaneous infantile haemangiomas,
      which may reflect differences in endothelial cell differentiation or underlying
      aetiology.

PMID- 17034539
TI  - Efalizumab-induced autoimmune pancytopenia.
AB  - Efalizumab is a recombinant, humanized monoclonal anti-CD11a antibody used for
      the treatment of moderate to severe plaque psoriasis. Immune-mediated
      thrombocytopenia and anaemia have previously been reported with this therapy. We
      describe the first case of immune-mediated pancytopenia in a patient treated with
      efalizumab. Close monitoring of all blood cell counts is warranted in light of
      this case.

PMID- 17034540
TI  - Childhood epidermolysis bullosa acquisita with autoantibodies against the
      noncollagenous 1 and 2 domains of type VII collagen: case report and review of
      the literature.
AB  - Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disease
      characterized by IgG autoantibodies to type VII collagen, a major component of
      anchoring fibrils. Most patients with EBA are adult and develop autoantibodies to
      the noncollagenous (NC) 1 domain of type VII collagen. We describe a 4-year-old
      Japanese boy presenting pruritic vesicles and tense blisters over his whole body.
      Immunofluorescence studies revealed linear IgG/C3 deposits along the dermal
      epidermal junction of the patient's skin, and circulating IgG autoantibodies
      mapping to the dermal side of 1 M NaCl-split skin. By immunoblotting analysis
      using dermal extracts as a substrate, the patient's IgG antibodies labelled a 290
      kDa protein corresponding to type VII collagen. Immunoblotting studies using
      recombinant proteins demonstrated that the patient's circulating autoantibodies
      recognized not only the NC1 but also the NC2 domain of type VII procollagen.
      Review of the previously reported cases and the present case suggested that
      patients with EBA with autoantibodies to regions other than the NC1 domain are
      all children younger than 10 years of age with clinical features of an
      inflammatory phenotype.

PMID- 17034541
TI  - Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade
      cutaneous B-cell lymphoma.
AB  - The chimeric anti-CD20 monoclonal antibody, rituximab, is a promising treatment
      for cutaneous B-cell lymphomas. Classically used in combination with a multiagent
      chemotherapy regimen, it can sometimes give excellent results alone. Because of
      its selective action on B lymphocytes, it is considered a moderate
      immunosuppressant in terms of infection. We describe a woman with relapsed
      cutaneous follicular centre B-cell lymphoma and secondary lymph-node involvement
      treated with rituximab alone, which induced a complete remission. One year later,
      she experienced a fatal hepatitis B virus (HBV) reactivation. Several such HBV
      reactivations were reported after combined rituximab and multiagent chemotherapy
      for B-cell lymphomas. This is the first case of HBV reactivation occurring during
      the year following rituximab monotherapy in the absence of any other
      immunosuppressive factor.

PMID- 17034542
TI  - Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant
      syndrome?
AB  - Members of two generations of a South African family have a unique syndrome
      comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis.
      The condition is clinically important as the skin changes, which involve the
      face, have considerable cosmetic impact, while lung involvement is potentially
      lethal in adulthood. Skin manifestations which facilitate diagnosis include
      facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal
      atrophy. The scalp, facial and body hair are fine and scanty. The tendon
      contractures lead to progressive digital flexion deformities and abnormalities of
      the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as
      progressive dyspnoea. Pedigree data are compatible with an autosomal dominant
      mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic
      and fibrous bands and not tendon contractures and is not associated with
      potentially lethal pulmonary fibrosis. Rather than name this disorder a variant
      of Weary syndrome, it might be prudent to use as an umbrella title one composed
      by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which
      variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis
      described as inconsistently associated with Weary syndrome) and HSP with
      tendon/pulmonary involvement (current family) may be classified. The
      manifestations in this family differ from other poikilodermata and, to the best
      of our knowledge, have not been previously documented.

PMID- 17034543
TI  - A case of epidermolysis bullosa simplex with a newly found missense mutation and
      polymorphism in the highly conserved helix termination motif among type I
      keratins, which was previously reported as a pathogenic missense mutation.

PMID- 17034544
TI  - A novel ABCA12 mutation 3270delT causes harlequin ichthyosis.

PMID- 17034545
TI  - A novel familial germline mutation in the initiator codon of the BHD gene in a
      patient with Birt-Hogg-Dube syndrome.

PMID- 17034546
TI  - Two novel TSC2 mutations in Chinese patients with tuberous sclerosis complex and
      a literature review of 20 patients reported in China.

PMID- 17034547
TI  - Penile argyria.

PMID- 17034548
TI  - Fatal erosive lichen planus.

PMID- 17034549
TI  - Two cases of delayed granulomatous reactions to the cosmetic filler Dermalive, a
      hyaluronic acid and acrylic hydrogel.

PMID- 17034550
TI  - Highly active antiretroviral therapy-induced regression of basal cell carcinomas
      in a patient with acquired immunodeficiency and Gorlin syndrome.

PMID- 17034551
TI  - Management of onychomycosis and awareness of guidelines among dermatologists.

PMID- 17034552
TI  - Phaeohyphomycosis caused by Exophiala salmonis.

PMID- 17034553
TI  - Presence of herpes simplex virus DNA in erythema multiforme but not polymorphic
      light eruption.

PMID- 17034554
TI  - Successful treatment of stucco keratosis with maxacalcitol.

PMID- 17034555
TI  - Eosinophilic cellulitis as a presenting feature of chronic eosinophilic
      leukaemia, secondary to a deletion on chromosome 4q12 creating the FIP1L1-PDGFRA
      fusion gene.

PMID- 17034556
TI  - Neutrophilic dermatosis of the dorsal hands treated with indomethacin.

PMID- 17034557
TI  - Alopecia areata associated with basal cell carcinoma developing within a naevus
      sebaceus.

PMID- 17034558
TI  - Low-resolution teledermatology.

PMID- 17034559
TI  - Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the
      population of Northern Germany.

PMID- 17034561
TI  - Proteus syndrome with agenesis of the rectus abdominis.

PMID- 17034562
TI  - Ustilago species infection in humans.

PMID- 17034563
TI  - Mycobacterium chelonae infection complicating cosmetic facial surgery.

PMID- 17034564
TI  - Sweet syndrome: vasculitis or not?

PMID- 17034565
TI  - Gefitinib-induced acute generalized exanthematous pustulosis in two patients with
      advanced non-small-cell lung cancer.

PMID- 17034566
TI  - Sweet syndrome associated with intrahepatic cholangiocarcinoma producing
      granulocyte colony-stimulating factor.

PMID- 17034567
TI  - Long-term infliximab for severe hidradenitis suppurativa.

PMID- 17034569
TI  - Functional roles of immature dendritic cells in impaired immunity of solid tumour
      and their targeted strategies for provoking tumour immunity.
AB  - Dendritic cells play a crucial role in initiating tumour immunity as well as in
      the immune response for invading foreign pathogens such as bacteria and viruses.
      For bacterial and viral infections, the immature dendritic cells (iDCs) residing
      in peripheral tissues are efficiently activated and matured by pathogen signals
      for performing the immune response. In contrast, for self-antigens, the naive T
      cells are not activated by iDCs but proceed to anergy/deletion, and the
      generation of regulatory T cells for immune tolerance. The induction of immune
      response and tolerance is regulated strictly by iDCs as the sensor for
      homeostasis of immune response in the host. Despite the identification of some
      tumour antigens, tumour immunity is not provoked successfully. Even though there
      are some critical obstacles to inhibit effective tumour immunity, tumour cells
      are able to exploit the functional roles of iDCs for tumour progression, which
      are induced by tumour-derived soluble factors such as vascular endothelial growth
      factor (VEGF) and functionally modulated in the microenvironment. The iDCs still
      remain as the critical target for provoking tumour immunity. In this review, the
      functional roles of tumour-associated iDCs and the strategy for targeting iDCs in
      effective tumour immunity for the cancer patient are discussed.

PMID- 17034570
TI  - Chronic Chlamydia pneumoniae infection may promote coronary artery disease in
      humans through enhancing secretion of interleukin-4.
AB  - Atherosclerosis is an inflammatory response, probably to a range of initiating
      causes. Chronic infection with Chlamydia pneumoniae (C.pn) has been suggested as
      one cause, but the nature of the association is controversial, in large part due
      to lack of an identified mechanism to link infection with the atherosclerotic
      process in man. This study examined 139 consecutive subjects with stable chest
      pain, with the aim of correlating the serological status of C.pn infection with
      the pattern of secretion of cytokines from CD4(+) T lymphocytes. C.pn
      seropositive subjects secreted significantly more interleukin (IL)-4 than did
      those who were C.pn seronegative (P = 0.02). No significant difference was noted
      for secreted interferon (IFN)-gamma. The amount of secreted IL-4, but not of
      secreted IFN-gamma, correlated positively with the extent of coronary artery
      disease (P = 0.006). A similar correlation with secreted IL-4 was not identified
      with Helicobacter pylori infection. These results support the hypothesis that
      C.pn infection contributes to the inflammatory process responsible for coronary
      artery atherosclerosis. The method used to detect cytokine secretion involves
      ligation of CD40L on blood CD4(+) T cells, which may have relevance to tissue
      events.

PMID- 17034571
TI  - Identification of key peptide-specific CD4+ T cell responses to human
      cytomegalovirus: implications for tracking antiviral populations.
AB  - Human cytomegalovirus (CMV) infection is normally controlled effectively by the
      immune response, including CD4(+) T cells. Large numbers of these cells are
      present in healthy seropositive individuals but their loss in immunosuppression
      leads to reactivation and disease. Tracking such responses in vivo is hampered by
      poor definition of their peptide targets. In this study, we defined the key
      targets of the peptide-specific CD4(+) T cell responses to the CMV pp65 protein
      using functional assays and a peptide library. Despite a good deal of
      interindividual variation in the numbers of peptides recognized, responses to CMV
      pp65 were strikingly targeted at three key epitopes. A response to one or more of
      these three key peptides was seen in all individuals tested (P < 0.0001) and this
      finding was tested and reproduced in a second independent population. The most
      common response identified was that to a DR53 restricted epitope, aa281-295. HLA
      DR1 restricted CMV pp65-specific populations, although reproducibly detected,
      were of low frequency ex vivo. However, it was possible to detect and phenotype
      these cells using an enrichment protocol and this revealed them to have 'effector
      memory' status although, in contrast to CD8(+) T cell responses, these were
      CD45RA(-). These data suggest that CD4(+) T cell responses to CMV can be
      identified reliably using a pool of just three peptides. This simple approach
      will provide a robust and reliable as well as economic method for tracking
      peptide specific populations in health and disease.

PMID- 17034572
TI  - Quantitative measurement of hepatitis C virus core antigen is affected by the
      presence of cryoglobulins.
AB  - Mixed cryoglobulinaemia is associated strikingly with HCV infection. The aim of
      this study was to assess whether the adherence to proper methods of collecting
      samples for cryoglobulin detection was critical or not on virological parameters
      in hepatitis C virus (HCV) patients. We studied 56 consecutive patients. Blood
      samples were collected using a conventional method and a blood collection method
      at 37 degrees C adapted to cryoglobulin detection. HCV core antigen and HCV RNA
      were measured in sera and cryoglobulins issued from both blood collection
      methods. In cryoglobulin-positive patients, serum concentrations of HCV core
      antigen, but not that of HCV RNA, were significantly higher when a conventional
      method was used, compared to a blood collection method at 37 degrees C (P =
      0.001). In the cryoprecipitates, concentration of HCV core antigen was optimum
      when the blood collection method at 37 degrees C, rather than the conventional
      method, was applied for cryoglobulin detection (P < 10(-4)). The recovery of HCV
      core antigen in the cryoprecipitate was improved when cryoglobulins were isolated
      using the blood collection method at 37 degrees C rather than the conventional
      method (P < 0.001). HCV parameter measurements and cryoglobulin study should not
      be performed on the same serum samples due to the potential impact of blood
      collection methods on results.

PMID- 17034573
TI  - Innate immune peptide LL-37 displays distinct expression pattern from beta
      defensins in inflamed gingival tissue.
AB  - Anti-microbial peptides produced from mucosal epithelium appear to play pivotal
      roles in the host innate immune defence system in the oral cavity. In particular,
      human beta-defensins (hBDs) and the cathelicidin-type anti-microbial peptide, LL
      37, were reported to kill periodontal disease-associated bacteria. In contrast to
      well-studied hBDs, little is known about the expression profiles of LL-37 in
      gingival tissue. In this study, the anti-microbial peptides expressed in gingival
      tissue were analysed using immunohistochemistry and enxyme-linked immunosorbent
      assay (ELISA). Immunohistochemistry revealed that neutrophils expressed only LL
      37, but not hBD-2 or hBD-3, and that such expression was prominent in the
      inflammatory lesions when compared to healthy gingivae which showed very few or
      no LL-37 expressing neutrophils. Gingival epithelial cells (GEC), however,
      expressed all three examined anti-microbial peptides, irrespective of the
      presence or absence of inflammation. Moreover, as determined by ELISA, the
      concentration of LL-37 in the gingival tissue homogenates determined was
      correlated positively with the depth of the gingival crevice. Stimulation with
      periodontal bacteria in vitro induced both hBD-2 and LL-37 expressions by GEC,
      whereas peripheral blood neutrophils produced only LL-37 production, but not hBD
      2, in response to the bacterial stimulation. These findings suggest that LL-37
      displays distinct expression patterns from those of hBDs in gingival tissue.

PMID- 17034574
TI  - Proviral load and immune markers associated with human T-lymphotropic virus type
      1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Peru.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is the aetiological agent of HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of
      this study is to identify which ex vivo and in vivo markers are associated
      independently with HAM/TSP in a Peruvian population. Eighty-one subjects (33
      men/48 women) were enrolled: 35 presented with HAM/TSP, 33 were asymptomatic HTLV
      1 carriers (ACs) and 13 were HTLV-1-seronegative controls (SCs). Ex vivo markers
      included T cell proliferation and Th1 [interferon (IFN)-gamma], Th2 [interleukin
      (IL)-4, IL-5], proinflammatory [tumour necrosis factor (TNF)-alpha] and anti
      inflammatory (IL-10) cytokine production in non-stimulated peripheral blood
      mononuclear cell (PBMC) cultures. In vivo CD4(+) T cell count, markers of Th1
      [interferon-inducible protein (IP)-10] and Th2 (sCD30) activity in plasma and
      HTLV-1 proviral load in PBMCs were also evaluated. In univariate analysis,
      several markers, including T cell proliferation, IFN-gamma, IP-10, sCD30 and
      proviral load were associated with HAM/TSP, but in a multiple logistic regression
      analysis only the proviral load remained associated significantly with disease
      manifestation [adjusted OR 9.10 (1.24-66.91)]. Our findings suggest that HAM/TSP
      is associated primarily with proviral load, whereas the observed association with
      some immune markers seems secondary.

PMID- 17034575
TI  - The T cell response to persistent herpes virus infections in common variable
      immunodeficiency.
AB  - We show that at least half of patients with common variable immunodeficiency
      (CVID) have circulating CD8(+) T cells specific for epitopes derived from
      cytomegalovirus (CMV) and/or the Epstein-Barr virus (EBV). Compared to healthy
      age-matched subjects, more CD8(+) T cells in CVID patients were committed to CMV.
      Despite previous reports of defects in antigen presentation and cellular immunity
      in CVID, specific CD4(+) and CD8(+) T cells produced interferon (IFN)-gamma after
      stimulation with CMV peptides, and peripheral blood mononuclear cells secreted
      perforin in response to these antigens. In CVID patients we found an association
      between a high percentage of circulating CD8(+) CD57(+) T cells containing
      perforin, CMV infection and a low CD4/CD8 ratio, suggesting that CMV may have a
      major role in the T cell abnormalities described previously in this disease. We
      also show preliminary evidence that CMV contributes to the previously unexplained
      severe enteropathy that occurs in about 5% of patients.

PMID- 17034576
TI  - Immune markers measured before treatment predict outcome of intensive phase
      tuberculosis therapy.
AB  - The development of a statistical model based on simple immunological markers
      which could predict the response to tuberculosis treatment would facilitate
      clinical trials of new anti-tuberculosis drugs. We have examined the ability of
      immunological biomarkers, measured at diagnosis and after 4 weeks of treatment,
      to predict sputum smear status at week 8. Eighteen tuberculosis patients with
      positive Ziehl-Nielsen (ZN)-stained sputum smears 8 weeks after initiation of
      treatment (slow response) were matched for age, gender, sputum smear grade and
      extent of disease on chest radiograph to 18 patients with negative sputum smears
      at week 8 (fast response). In addition to total white blood cell (WBC) counts and
      absolute lymphocyte, monocyte and neutrophil numbers, concentrations of six serum
      markers were measured by enzyme-linked immunosorbent assay (ELISA) in all
      patients (soluble interleukin-2 receptor alpha (sIL-2Ralpha), granzyme B, soluble
      tumour necrosis factor alpha receptors 1 and 2 (sTNF-R1 and -2), nitrotyrosine
      and interferon-gamma (IFN-gamma). At diagnosis, 4 biomarkers (sTNF-R1, total WBC,
      absolute monocyte and absolute neutrophil numbers) were significantly higher in
      slow response patients. At week 4, total WBC count and absolute monocyte and
      neutrophil numbers remained significantly higher in slow responders. Discriminant
      analysis of the diagnosis and week 4 data provided models for classification of
      slow response patients with 67% and 83% predictive accuracy. We suggest that
      treatment response phenotypes can be determined before the start of treatment.
      Reliable predictive models would allow targeted interventions for patients at
      risk for slow treatment response to standard tuberculosis therapy.

PMID- 17034577
TI  - Expression and function of the purinergic receptor P2X7 in patients with
      pulmonary tuberculosis.
AB  - P2X(7) is a channel receptor gated by adenosine triphosphate (ATP) that is
      involved in the killing of intracellular mycobacteria. To explore further the
      role of P2X(7) in immunity against Mycobacterium tuberculosis, we studied its
      expression and function in 19 patients with pulmonary tuberculosis (TB) and 19
      healthy contacts. Flow cytometry analysis showed a similar and variable
      expression of P2X(7) in TB patients and healthy subjects. In contrast, P2X(7)
      mARN levels were significantly higher in TB patients. When the function of the
      P2X(7) receptor in peripheral blood mononuclear cells (PBMC) was assessed by the
      effect of exogenous ATP on apoptosis, the uptake of the fluorescent marker
      Lucifer yellow or extracellular signal regulated kinase (ERK) phosphorylation, no
      significant differences were detected in patients and controls. However, mRNA
      macroarray analysis showed that upon stimulation with ATP, the PBMC from TB
      patients showed a significant induction of a higher number of cytokine genes (27
      of 96), and a lower number of apoptosis genes (20 of 96) compared to healthy
      controls (17 and 76 genes, respectively). These results suggest that although the
      PBMC from TB patients do not show apparent abnormalities in the expression of
      P2X(7), and the intracellular signals generated through it, the pattern of gene
      expression induced by ATP in these cells is different from that found in healthy
      contacts. This phenomenon suggests a defective function of P2X(7) in the immune
      cells from TB patients, a condition that may contribute to the inability of these
      patients to eliminate the mycobacteria.

PMID- 17034578
TI  - Autoantibodies against CD28 are associated with atopic diseases.
AB  - The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T cell activation and
      tolerance. Autoantibodies to surface molecules on lymphocytes have already been
      described in various immune conditions, such as autoimmune diseases, infections
      and blood transfusions. The objective of this study was to test sera from healthy
      individuals and from patients for association of CD28 autoantibodies with
      inflammatory and non-inflammatory diseases. First, CD28 was obtained by digestion
      of CD28-Ig fusion protein with trypsin. The cleavage products were separated by
      sodium dodecyl sulphate-page gel electrophoresis. Additionally, a CD28/GST fusion
      protein was expressed in Escherichia coli and was used to establish an enzyme
      linked immunosorbent assay for detection of autoantibodies against CD28. Sera
      from healthy individuals (n = 72) and patients with different inflammatory and
      non-inflammatory skin diseases (n = 196) were tested for the presence of
      autoantibodies against CD28. Using mixed lymphocyte reaction (MLR), purified
      autoantibodies against CD28 were tested for their effects on CTLA-4-Ig-induced T
      cell anergy. In this study, for the first time, we describe the existence of
      autoantibodies against CD28 in humans which are associated with atopic diseases,
      e.g. allergic rhinitis and asthma. These antibodies stimulate T cells and
      overcome the CTLA-4-Ig-induced anergy of T cells in an MLR. The existence of
      autoantibodies against CD28, which may have a T cell-stimulating function, has
      been shown. The data indicate that autoantibodies against CD28 could be a new
      immunological mechanism in allergic inflammation. Additionally, autoantibodies
      against CD28 could be an important new marker to discriminate between atopic
      diseases and other inflammatory skin diseases.

PMID- 17034579
TI  - T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and
      CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients
      during treatment with interferon alpha plus ribavirin: analysis in a population
      on effective antiretroviral therapy.
AB  - Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the
      treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus
      (HIV)-co-infected patients. To increase the knowledge about this secondary
      effect, we performed an analysis of the evolution of the T cell receptor excision
      circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+)
      subpopulations during the treatment of chronic hepatitis HCV with peginterferon
      alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with
      undetectable HIV load after highly active antiretroviral therapy (HAART), were
      treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time
      polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and
      CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median
      baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively.
      Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T
      lymphocytes. A progressive decrease in both T cell populations, as well as of
      their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference
      between the baseline and nadir levels approaching 50%. The evolution of T cell
      populations and TRECs was independent of the response to the treatment. T
      lymphocytes and their subpopulations returned to baseline levels at 24 weeks
      after the end of treatment, with the exception of the T CD4(+) CD45RA(+)
      subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89
      (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not
      return to the basal values. In conclusion, a significant reduction of CD4(+) and
      CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV
      co-infected patients treated with pegIFN-alpha was observed. Both subpopulations
      increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation
      did not reach the basal levels as a consequence, at least in part, of a decrease
      in thymic production.

PMID- 17034580
TI  - Complement membrane attack is required for endplate damage and clinical disease
      in passive experimental myasthenia gravis in Lewis rats.
AB  - Myasthenia gravis (MG) is a debilitating and potentially fatal neuromuscular
      disease characterized by the generation of autoantibodies reactive with nicotinic
      acetylcholine receptors (AChR) that cause loss of AChR from the neuromuscular
      endplate with resultant failure of neuromuscular transmission. A role for
      complement (C) in the pathology of human MG has been suggested based upon
      identification of C activation products in plasma and deposited at the endplate
      in MG. In the rat model, experimental autoimmune MG (EAMG), C depletion or
      inhibition restricts clinical disease, further implicating C in pathology. The
      mechanisms by which C activation drives pathology in MG and EAMG are unclear.
      Here we provide further evidence implicating C and specifically the membrane
      attack complex (MAC) in the Lewis rat passive EAMG model of MG. Rats deficient in
      C6, an essential component of the MAC, were resistant to disease induction and
      endplate destruction was reduced markedly compared to C6-sufficient controls.
      After reconstitution with C6, disease severity and endplate destruction in the C6
      deficient rats was equivalent to that in controls. The data confirm the essential
      role of the MAC in the destruction of the endplate in EAMG and raise the prospect
      of specific MAC inhibition as an alternative therapy in MG patients resistant to
      conventional treatments.

PMID- 17034581
TI  - Remission of collagen-induced arthritis is associated with high levels of
      transforming growth factor-beta expression in the joint.
AB  - Immunization of genetically susceptible strains of mice with heterologous type II
      collagen leads to the induction of a self-limiting polyarthritis that begins to
      subside around 10 days after onset of clinical disease. The aims of this study
      were to compare pro- and anti-inflammatory cytokine expression in the joints
      during the course of arthritis in order to identify cytokines involved in
      spontaneous remission of arthritis. DBA/1 mice were immunized with type II
      collagen and an immunohistochemical analysis of expression of proinflammatory
      cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6]
      and anti-inflammatory cytokines [IL-10, IL-1ra, transforming growth factor (TGF)
      beta1, TGF-beta2 and TGF-beta3] in joints was carried out over the course of the
      disease. Both pro- and anti-inflammatory cytokines were found to be expressed in
      early arthritis. However, around 10 days after onset of arthritis, the level of
      expression of proinflammatory cytokines declined while the level of expression of
      anti-inflammatory cytokines, particularly TGF-beta1 and TGF-beta2, increased.
      Surprisingly, TNF-alpha continued to be expressed at low levels during the period
      of disease remission (30 days after onset). Blockade of TNF-alpha during the
      period of disease remission had no effect on TGF-beta expression. This study
      confirms that the level of inflammation in arthritis correlates strongly with the
      balance of pro- and anti-inflammatory cytokine expression in the joints. Of the
      anti-inflammatory cytokines studied, TGF-beta1 and TGF-beta2 predominate during
      the time of disease remission, suggesting that these cytokines are involved in
      regulating disease activity.

PMID- 17034583
TI  - Phenotypic features of circulating leucocytes as immunological markers for
      clinical status and bone marrow parasite density in dogs naturally infected by
      Leishmania chagasi.
AB  - Canine visceral leishmaniasis (CVL) manifests itself as a broad clinical spectrum
      ranging from asymptomatic infection to patent severe disease. Despite relevant
      findings suggesting changes on lymphocytes subsets regarding the CVL clinical
      forms, it still remains to be elucidated whether a distinct phenotypic profile
      would be correlated with degree of tissue parasite density. Herein, we have
      assessed the correlation between the clinical status as well as the impact of
      bone marrow parasite density on the phenotypic profile of peripheral blood
      leucocytes in 40 Brazilian dogs naturally infected by Leishmania chagasi. Our
      major findings describe the lower frequency of B cells and monocytes as the most
      important markers of severe CVL. Our main statistically significant findings
      reveal that the CD8(+) T cell subset reflects most accurately both the clinical
      status and the overall bone marrow parasite density, as increased levels of
      CD8(+) lymphocytes appeared as the major phenotypic feature of asymptomatic
      disease and dogs bearing a low parasite load. Moreover, enhanced major
      histocompatibility complex (MHC)-II density as well as a higher CD45RB/CD45RA
      expression index seems to represent a key element to control disease morbidity.
      The association between clinical status, bone marrow parasitism and CD8(+) T
      cells re-emphasizes the role of the T cell-mediated immune response in the
      resistance mechanisms during ongoing CVL. Higher levels of circulating T
      lymphocytes (both CD4(+) and CD8(+) T cells) and lower MHC-II expression by
      peripheral blood lymphocytes seem to be the key for the effective immunological
      response, a hallmark of asymptomatic CVL.

PMID- 17034582
TI  - The membrane attack pathway of complement drives pathology in passively induced
      experimental autoimmune myasthenia gravis in mice.
AB  - The human neuromuscular disease myasthenia gravis (MG) is characterized by the
      generation of autoantibodies reactive with nicotinic acetylcholine receptors
      (AChR) that cause loss of AChR from the neuromuscular end-plate with resultant
      failure of neuromuscular transmission. A role for complement (C) in AChR loss has
      been suggested based upon morphological identification of C at the end-plate in
      MG and from the effects of C inhibition in murine models. Here we provide further
      evidence implicating C, and specifically the membrane attack complex (MAC), in a
      mouse model of MG. Mice deficient in the C regulators Daf1 and/or Cd59a were
      tested in the model. Wild-type mice were resistant to disease while mice
      deficient in Daf1 had mild disease symptoms with evidence of C activation and
      AChR loss at end-plates. Cd59a-deficient mice had very mild disease with some
      muscle inflammation and essentially undamaged end-plates. In contrast, mice
      deficient in both C regulators developed a severe paralytic disease with marked
      muscle inflammation and loss of end-plates. Inhibition of MAC assembly abrogated
      clinical disease in these double-deficient mice, demonstrating conclusively that
      MAC formation was driving pathology in the model. These findings provoke us to
      suggest that current anti-C therapeutics targeting MAC assembly will be
      beneficial in MG patients resistant to conventional therapies.

PMID- 17034584
TI  - Alcohol-induced gastritis prevents oral tolerance induction in mice.
AB  - Despite several reports on the immunological relationship between inflammatory
      bowel diseases and immunoregulatory mechanisms in the gut, systematic studies
      addressing the impact of inflammatory processes in the gastric mucosa on events,
      such as oral tolerance, are still limited. Herein, we report the establishment of
      a novel murine model of gastritis induced by short-term administration of
      ethanol. The major immumological features of this clinical entity are
      characterized, as well as its impact on the induction of oral tolerance. Our data
      demonstrate that ethanol ingestion during 4 consecutive days triggered an acute
      inflammatory reaction in the stomach referred as ethanol-induced gastritis and
      characterized by hyperaemia, oedema and mixed mononuclear/polymorphonuclear cell
      infiltrate. Besides local immunological changes, such as high levels of gastric
      interleukin (IL)-4 and interferon (IFN)-gamma, systemic alterations are also
      observed, including increased IL-4 synthesis, enhanced levels of serum IgE and
      absence of IL-10 production by spleen cells. Moreover, ethanol-induced gastritis
      prevents oral tolerance induction to ovalbumin (OVA) as demonstrated by unaltered
      anti-OVA humoral and cellular immune responses in treated animals. Tissue
      eosinophilia after footpad immunization with OVA suggests that oral treatment
      with ethanol induced an allergic-type reaction. Taken together, our findings
      indicate that short-term ethanol ingestion is associated with gastric
      inflammatory events able to break immunoregulatory mechanisms that maintain
      mucosal homeostasis and oral tolerance.

PMID- 17034585
TI  - The myeloid differentiation factor 88 is dispensable for the development of a
      delayed host response to Pseudomonas aeruginosa lung infection in mice.
AB  - Because MyD88 transduces a core set of Toll-like receptor (TLR)-induced signals,
      microbial-induced host responses can be divided broadly into the MyD88-dependent
      and MyD88-independent pathways. A specific pathogen induces a distinct pattern of
      host response dependent upon the signalling pathways employed. Recently, we
      demonstrated that a MyD88-dependent pathway is essential for the development of
      early (4-8 h) host response to Pseudomonas aeruginosa lung infection. Here, we
      show that the development of a delayed (24-48 h) host response to P. aeruginosa
      is independent of MyD88. Using MyD88-deficient mice, the production of macrophage
      inflammatory protein 2, tumour necrosis factor and interleukin 1alpha in the
      airway was observed following P. aeruginosa lung infection for 24 or 48 h.
      Moreover, the MyD88-deficient mice recruited sufficient neutrophils in the lung
      and cleared the bacteria efficiently from the lung after 48 h. Thus, the full
      development of host responses to P. aeruginosa lung infection involves, in a
      sequential, stepwise fashion, a MyD88-dependent early response and a MyD88
      independent delayed mechanism.

PMID- 17034586
TI  - Interferon-gamma is causatively involved in experimental inflammatory bowel
      disease in mice.
AB  - Cytokines may be crucially involved in the pathogenesis of inflammatory bowel
      diseases (IBD), but it remains controversial whether interferon (IFN)-gamma, a
      typical proinflammatory cytokine, is an essential mediator to cause the
      disorders. In the present study, IFN-gamma(-/-) and wild-type (WT) C57BL/6 mice
      were fed 2.5% dextran sodium sulphate (DSS) in drinking water for 7 days, in
      order to investigate DSS-induced intestinal inflammation. The DSS-treated WT mice
      exhibited a robust production of IFN-gamma in the gut, a remarkable loss of body
      weight, as well as high rate of mortality (60%). In striking contrast, IFN-gamma
      deficient mice did not develop DSS-induced colitis, as indicated by the
      maintenance of body weight and survival rate of 100%. Severe intestinal
      inflammation was demonstrated exclusively in WT animals in terms of the
      shortening of the bowel as well as the elevation of the disease activity index,
      myeloperoxidase (MPO) activity and serum haptoglobin level. Histological study of
      DSS-treated WT intestine revealed disruption of mucosal epithelium and massive
      infiltration of inflammatory cells, while the organ from IFN-gamma(-/-) mice
      remained virtually normal in appearance. Enzyme-linked immunosorbent assay
      (ELISA) analyses indicated abundant production of three chemokines, i.e. monokine
      induced by interferon-gamma (MIG), interferon-inducible protein 10 (IP-10) and
      monocyte chemoattractant protein-1 (MCP-1), in the DSS-irritated intestine of WT
      but not of IFN-gamma(-/-) mice. The present results demonstrate clearly that IFN
      gamma plays indispensable roles in the initiation of DSS colitis, and some
      chemokines are produced in an IFN-gamma-dependent fashion.

PMID- 17034587
TI  - Glomerular expression and elevated serum Bcl-2 and Fas proteins in lupus
      nephritis: preliminary findings.
AB  - Programmed cell death (apoptosis) is involved in glomerular injuries leading to
      glomerulonephritis. Bcl-2 and Fas are proteins that promote cell survival and
      death, respectively. This study tests the hypothesis that lupus nephritis is
      associated with alterations of Bcl-2 and Fas protein expression. Thirty-six
      patients with lupus nephritis and 10 controls (normal individuals) were included
      in this study. Bcl-2 and Fas positive cells were examined in kidney biopsies by
      immunohistochemistry. Bcl-2 and Fas serum levels were evaluated by enzyme-linked
      immunosorbent assay (ELISA). In the glomeruli of normal kidneys, Bcl-2 and Fas
      proteins were completely absent. In lupus nephritis patients, glomerular
      expression of Bcl-2 and Fas was seen in mesangial cells (1.3 +/- 0.1 and 2.0 +/-
      0.1 for Bcl-2 and Fas, respectively). Similarly, a statistically significantly
      higher Bcl-2 (217.1 +/- 85.9) and Fas (767.9 +/- 271) serum levels were found in
      lupus patients compared to controls (148.6 +/- 87, 550.3 +/- 91 for Bcl-2 and
      Fas, P < 0.05). A direct correlation between serum Bcl-2 and Fas and chronicity
      index was also found. Compared to normal controls, lupus nephritis is associated
      with glomerular expression and elevated serum levels of Bcl-2 and Fas proteins.
      These findings suggest possible roles for Bcl-2 and Fas in glomerular injury
      during evolution of lupus nephritis. The diagnostic, prognostic and therapeutic
      ramifications of our findings are open to further investigation.

PMID- 17034588
TI  - The highly attenuated vaccinia virus strain modified virus Ankara induces
      apoptosis in melanoma cells and allows bystander dendritic cells to generate a
      potent anti-tumoral immunity.
AB  - Vaccinia virus (VV) has been tested as oncolytic virus against malignant melanoma
      in clinical trials for more than 40 years. Until now, mainly strains comparable
      to viral strains used for smallpox vaccination have been probed for anti-tumoral
      therapy. We have shown recently that the wild-type strain Western Reserve (WR)
      can interfere with crucial functions of monocyte-derived dendritic cells (DCs).
      Our aim was to examine whether viral immune evasion mechanisms might be
      responsible for the ineffectiveness of WR-based vaccination strategies and
      whether the highly attenuated strain modified virus Ankara (MVA) differs from WR
      with respect to its possible immunostimulatory capacity after intratumoral
      injection. Using in vitro experiments, we compared the effect of both strains on
      melanoma cells and on local bystander DCs. We found that both VV-strains infected
      melanoma cells efficiently and caused disintegration of the actin cytoskeleton,
      as shown by fluorescence microscopy. In addition, both VV-strains caused
      apoptotic cell death in melanoma cells after infection. In contrast to MVA, WR
      underwent a complete viral replication cycle in melanoma cells. Bystander DCs
      were consecutively infected by newly generated WR virions and lost their capacity
      to induce allogeneic T cell proliferation. DCs in contact with MVA-infected
      melanoma cells retained their capacity to induce T cell proliferation. Immature
      DCs were capable of phagocytosing MVA-infected melanoma cells. Priming of
      autologous CD8(+) T cells by DCs that had phagocytosed MVA-infected, MelanA
      positive melanoma cells resulted in the induction of T cell clones specifically
      reactive against the model antigen MelanA as shown by enzyme-linked immunospot
      (ELISPOT) analysis. We conclude that the clinical trials with oncolytic wild-type
      VV failed probably because of suppression of bystander DCs and consecutive
      suppression of T cell-mediated anti-melanoma immunity. The attenuated VV-strain
      MVA facilitates the generation of tumour associated antigen (TAA)-specific T cell
      response as it is oncolytic for melanoma cells, but non-toxic for DC, and should
      be a promising candidate for intralesional metastatic melanoma therapy.

PMID- 17034589
TI  - Effect of serotonin on the differentiation of human monocytes into dendritic
      cells.
AB  - The local cytokine environment and presence of stimulatory signals determine
      whether monocytes acquire dendritic cell (DC) or macrophage characteristics and
      functions. Because enhanced platelet activation is reported in patients with many
      allergic disorders, such as atopic dermatitis, platelet-derived factors may
      influence monocytic differentiation into DC. In this study we examined the effect
      of serotonin, a prototypic mediator of allergic inflammation released mainly by
      activated platelets at the inflammatory site, on the granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation
      of monocytes into monocyte-derived DC. Monocytes from healthy adult donors were
      cultured with GM-CSF and IL-4 in the presence or absence of serotonin, and the
      phenotypes and function of these cells were analysed. In the presence of
      serotonin, monocytes differentiated into DC with reduced expression of co
      stimulatory molecules and CD1a, whereas expression of CD14 was increased. These
      serotonin-treated DC exhibited significantly reduced stimulatory activity toward
      allogeneic T cells. However, these cells showed enhanced cytokine-producing
      capacity, including IL-10 but not IL-12. There was no significant difference
      between both types of DC in phagocytic activity. Experiments using agonists and
      antagonists indicated that serotonin 5-hydroxytryptamine (5-HT) induced the
      alteration of their phenotype and reduction in antigen-presenting capacity were
      mediated via 5-HTR(1/7). It is therefore suggested that serotonin-driven DC may
      have a regulatory function in the inflammatory process.

PMID- 17034591
TI  - Can prostate cancer targets be achieved?

PMID- 17034590
TI  - Hypoxia induces expression of connective tissue growth factor in scleroderma skin
      fibroblasts.
AB  - Connective tissue growth factor (CTGF) plays a role in the fibrotic process of
      systemic sclerosis (SSc). Because hypoxia is associated with fibrosis in several
      profibrogenic conditions, we investigated whether CTGF expression in SSc
      fibroblasts is regulated by hypoxia. Dermal fibroblasts from patients with SSc
      and healthy controls were cultured in the presence of hypoxia or cobalt chloride
      (CoCl(2)), a chemical inducer of hypoxia-inducible factor (HIF)-1alpha.
      Expression of CTGF was evaluated by Northern and Western blot analyses. Dermal
      fibroblasts exposed to hypoxia (1% O(2)) or CoCl(2) (1-100 microM) enhanced
      expression of CTGF mRNA. Skin fibroblasts transfected with HIF-1alpha showed the
      increased levels of CTGF protein and mRNA, as well as nuclear staining of HIF
      1alpha, which was enhanced further by treatment of CoCl(2). Simultaneous
      treatment of CoCl(2) and transforming growth factor (TGF)-beta additively
      increased CTGF mRNA in dermal fibroblasts. Interferon-gamma inhibited the TGF
      beta-induced CTGF mRNA expression dose-dependently in dermal fibroblasts, but
      they failed to hamper the CoCl(2)-induced CTGF mRNA expression. In addition,
      CoCl(2) treatment increased nuclear factor (NF)-kappaB binding activity for CTGF
      mRNA, while decreasing IkappaBalpha expression in dermal fibroblasts. Our data
      suggest that hypoxia, caused possibly by microvascular alterations, up-regulates
      CTGF expression through the activation of HIF-1alpha in dermal fibroblasts of SSc
      patients, and thereby contributes to the progression of skin fibrosis.

PMID- 17034592
TI  - Urological cancer guidelines: are there any differences?

PMID- 17034593
TI  - WWW; the wild, wild web: internet usage in patients with urological cancer.

PMID- 17034594
TI  - Urological management of 'page kidney'.

PMID- 17034595
TI  - Results of a definitive study are needed to provide guidance on the treatment of
      patients with screen-detected, 'low-grade' prostate cancer.

PMID- 17034596
TI  - The enlarged prostate: a brief history of its surgical treatment.

PMID- 17034597
TI  - Congenital urethral obstruction: the video-endoscopic perspective.

PMID- 17034598
TI  - Risk factors and prevention of rhabdomyolysis after laparoscopic nephrectomy.

PMID- 17034599
TI  - Urinary symptom flare after brachytherapy for prostate cancer is associated with
      erectile dysfunction and more urinary symptoms before implantation.
AB  - OBJECTIVE: To examine the relationship of 'symptom flare' with sexual function
      and lower urinary tract symptoms (LUTS) before brachytherapy, as we noted that
      after brachytherapy for prostate cancer, some patients had recurrent LUTS after
      an asymptomatic period; this secondary exacerbation of symptoms ('symptom flare')
      occurred at approximately 2 years after implantation and was transient in most
      patients. PATIENTS AND METHODS: In all, 854 patients with organ-confined prostate
      carcinoma had transrectal ultrasonography-guided transperineal 125I interstitial
      brachytherapy of the prostate gland between June 1991 and September 2002, and
      were considered candidates for this study. Detailed information on urinary
      function was self-administered and prospectively collected before treatment and
      at intervals using the International Prostate Symptom Score (IPSS). Sexual
      function was evaluated with the Sexual Health Inventory for Men (SHIM), a five
      question, self-administered diagnostic test that can help to indicate the
      presence or absence of erectile dysfunction (ED). We used previously established
      criteria to estimate the risk of prostate-specific antigen (PSA) failure by
      dividing the men into three risk groups, i.e. low-risk, with a PSA level of < or
      = 10 ng/mL, stage < or = T2a, Gleason < or = 6; medium-risk, with a PSA level of
      < or = 15 ng/mL, Gleason 7 or stage T2b; and high-risk, with a PSA level of > 15
      ng/mL, stage > T2b, or Gleason > or = 8. RESULTS: There was a significant
      association of flare with ED; men with flare reported significantly more ED than
      men without (P = 0.020). Men with high-risk disease reported more ED because they
      received more intensive treatment (hormones and increased radiation dose) than
      men with medium- or low-risk disease. To correct for this confounding factor,
      multivariate linear regression was used; the regression was significant overall
      (P < 0.001), and the effects of risk group (P < 0.001) and flare (P < 0.026) on
      SHIM score were significant and independent of each other. Flare was also
      significantly associated with a higher pre-implant IPSS; the probability of flare
      was 62% for a pre-implant IPSS of zero, to 94% for an IPSS of 30. CONCLUSIONS:
      Radiation reaction and radiation sensitivity contribute to ED and greater LUTS in
      men who have had brachytherapy for prostate cancer. This contribution is evident,
      e.g. in men with ataxia-telangiectasia (ATM) gene mutations. Sequence variants in
      the ATM gene, particularly those that encode for an amino-acid substitution, are
      associated with adverse radiotherapy responses among patients treated with 125I
      prostate brachytherapy. Our finding of the association of urinary symptom flare
      with ED suggests it would be worthwhile to determine whether sildenafil is as
      effective in men with flare, and if not, whether higher sildenafil doses would be
      of value. Alternatively, alpha1-selective adrenoceptor-blocking agents, e.g.
      terazosin, combined with sildenafil, might be of benefit. Also, patients with a
      high IPSS before brachytherapy can be warned that they have a greater risk of
      flare and ED.

PMID- 17034600
TI  - Predictive value of prostatic adenocarcinoma after a negative prostate biopsy.
AB  - OBJECTIVE: To investigate the predictive value (PV) for all prostate cancers and
      for clinically significant cancer undiagnosed after a 10-core biopsy protocol, as
      the 10-core transrectal ultrasonography-guided biopsy is considered the standard
      technique of prostatic biopsy due to its high rate of detection of prostatic
      adenocarcinoma. PATIENTS AND METHODS: In all, 132 consecutive radical
      prostatectomy (RP) specimens, with their corresponding 10-core biopsies, were
      reviewed. Cases with unilateral core involvement by prostate cancer were retained
      for study. Morphometric analysis was conducted on the biopsy-negative hemi
      prostates to determine the PV of the biopsy protocol with respect to the size,
      position and clinical significance of the lesion. RESULTS: In all, 70 resected
      prostates (RP) had unilateral core involvement by prostate cancer. In 38 cases,
      there was cancer in the biopsy-negative hemi-prostates (group 1); in the
      remaining 32 the hemi-prostates were free of cancer (group 2). Group 1 was
      categorized by morphometric criteria. Specifically, 23 cases had one to eight
      foci of prostate cancer in the posterior nontransitional zone (NTZ) (group 1a),
      while 15 had two to six foci of prostate cancer in the transitional zone (TZ), or
      the anterior horn (AH) of the peripheral zone or the TZ and AH (group 1b). There
      were two cases with clinically significant prostate cancer in group 1a, and six
      in group 1b. CONCLUSIONS: The PV of a negative five-core biopsy protocol on a
      hemi-prostate is 54% for prostate cancer and 11% for clinically significant
      prostate cancer. Most clinically significant prostate cancers were in the AH/TZ
      of the prostate.

PMID- 17034601
TI  - Prostate-specific antigen testing: uncovering primary care influences.
AB  - OBJECTIVES: To examine influences on the behaviour of General Practitioner (GP)
      in relation to prostate-specific antigen (PSA) testing. SUBJECTS AND METHODS: In
      Northern Ireland in 2003-2004, all GPs (1067) were invited to complete a self
      administered postal questionnaire survey that was then matched with a regional
      PSA-testing database. The main outcome measures were individual GP responses for
      demographic, practice and training characteristics, PSA testing behaviour and
      perceived influences, matched against GP-initiated first PSA tests performed in
      2003 and 2004 (22 207 tests). RESULTS: In all, 704 GPs (66%) responded and 49% of
      these reported awareness of the national guidelines, which was highest among
      those attending postgraduate meetings. PSA tests were more likely to be ordered
      by full-time male GPs who had attended a local postgraduate urology meeting; ran
      a 'well-man' clinic; tested men with unrelated complaints; and were not in a
      training practice. Testing levels were highest among GPs who had been practising
      for 21-30 years and those in rural practices. Awareness of national guidelines or
      having had a postgraduate post in urology did not affect testing behaviour. After
      adjusting for gender, working hours, duration in practice and urban/rural
      setting, independent influences increasing testing behaviour were: testing men
      with a positive family history or unrelated complaints; testing any man who
      requests it; and previous experience of prostate cancer being detected in an
      asymptomatic patient by PSA testing. Working in an accredited training practice
      was associated with lower testing levels. CONCLUSION: There are complex
      influences on the PSA testing behaviour of GPs; addressing these influences could
      contribute to the rationalization of testing. A low awareness of national
      guidelines indicates a need for new strategies to disseminate and implement
      guidelines. The influence of local educational meetings on PSA testing is an
      unharnessed force.

PMID- 17034602
TI  - Carefully selected intratesticular lesions can be safely managed with serial
      ultrasonography.
AB  - OBJECTIVE: To evaluate a policy of conservative non-operative management for
      incidental, impalpable, < 1 cm, intratesticular pathology. PATIENTS AND METHODS:
      We retrospectively reviewed all scrotal ultrasonograms within an 8-year period to
      identify all radiological lesions of < 1 cm within the testis. All palpable
      lesions and those accompanied by elevated tumour markers or disseminated
      malignancy were managed surgically. The remaining incidentally detected lesions
      were followed with a protocol of serial ultrasonography (US). RESULTS: Of 1544
      scans reviewed, 12 (0.8%) lesions suitable for observational management were
      identified. The mean (range) age of the patients was 54 (34-76) years. The
      indication for US was suspected epididymitis in five, contralateral epididymal
      cyst in five and infertility in two patients. The mean (range) size of the lesion
      was 4.9 (1.5-9.8) mm. Three anechoic lesions were consistent with intratesticular
      cysts, and each was followed with no change to a mean (range) follow-up of 26 (12
      48) months. Eight hypoechoic lesions were followed to a mean of 34 (4-72) months,
      and only one showed growth on repeat US after an interval of 4 months, and was
      diagnosed as a 1.0-cm seminoma after orchidectomy. One hyperechoic lesion remains
      unchanged at 6 months of follow-up. CONCLUSION: Supported by previous reports
      suggesting that most testis lesions of < 1 cm are benign, we managed a series of
      carefully selected intratesticular lesions conservatively, the behaviour in most
      being in keeping with benign pathology.

PMID- 17034603
TI  - Surgical treatment for urethral recurrence after ileal neobladder reconstruction
      in patients with bladder cancer.
AB  - OBJECTIVE: To report a retrospective study evaluating the management of
      superficial urethral recurrence after ileal neobladder construction in patients
      with bladder cancer. PATIENTS AND METHODS: In 77 consecutive patients with ileal
      neobladder after radical cystectomy for invasive bladder cancer, urethral
      recurrence was evaluated and transurethral resection (TUR) used as an initial
      treatment for superficial urethral recurrence. Urethrectomy with urinary re
      diversion was performed when further recurrence developed. RESULTS: Four patients
      (5%) presented with a superficial urethral recurrence and all four were treated
      by TUR as initial therapy. One patient has had no evidence of recurrence after
      initial TUR, although the other three patients were later treated with salvage
      urethrectomy due to repeated urethral recurrence. As a result, the stage of
      urethral recurrence advanced from pTa to pT1-pT2 in two of the three patients.
      For urinary re-diversion, one patient had a conversion from a Studer pouch to an
      ileal conduit, using the afferent limb, and the other two were converted from a
      Hautmann pouch to a continent reservoir using the Appe-Mainz procedure. There was
      no evidence of metastasis or local recurrence in any of the four patients.
      CONCLUSION: Urethral preservation at initial therapy for superficial recurrence
      might be reasonable, and sequential urethrectomy after attempted urethral
      preservation might be strategically feasible. Urinary re-diversion from a
      neobladder to a catheterizable continent reservoir using the appendix would be a
      good choice and maintains the quality of life.

PMID- 17034604
TI  - Adjuvant intravesical therapy based on an in vitro cytotoxicity assay in the
      management of superficial transitional cell cancer of the urinary bladder.
AB  - OBJECTIVE: To investigate the utility of an individualized chemo/immunotherapy
      regimen of intravesical therapy based on the results of an assessment of in vitro
      cytotoxicity. PATIENTS AND METHODS: Intravesical adjuvant chemo/immunotherapy was
      given to 47 patients based on the results of in vitro cytotoxicity assay of the
      responses of cultured autologous tumour cells to various cytotoxic drugs
      (mitomycin-C, doxorubicin and cisplatin) and immunomodulating agents (bacillus
      Calmette-Guerin, BCG and interferon-alpha2b). Intravesical therapy was given as
      single- or double-drug regimens according to the assay results: 16 (34%) patients
      showed cytotoxicity to a single drug and 31 (66%) showed maximum cytotoxicity to
      a combination of immunomodulators and cytotoxic agents. The efficacy of treatment
      in terms of tumour-free survival and recurrence rate was compared with 40
      patients receiving intravesical BCG according to International Protocol (control
      group). RESULTS: In the in vitro assay group, seven patients (15%) had tumour
      recurrence, compared to 15 (38%) in the control group (P = 0.02). In the in vitro
      group, one of 16 patients on a single drug and six on the double-drug regimen had
      a recurrence. The patients given BCG with cytotoxic drugs had no recurrences, but
      29% of patients given interferon-alpha2b combinations had recurrences. Kaplan
      Meier analysis showed a longer recurrence-free survival in the in vitro group
      (75%) than in the control group (49%) at 48 months of follow-up. CONCLUSION:
      Intravesical therapy based on an in vitro cytotoxicity assay is an attempt to
      give individualized therapy, and to increase tumour-free survival in these
      patients, with no side-effects. Recurrences in seven patients in the in vitro
      group might be due to a defective host immune response, or to expansion of a
      subclone of tumour cells resistant to all treatment.

PMID- 17034605
TI  - A randomized controlled trial of the effectiveness of pelvic floor therapies for
      urodynamic stress and mixed incontinence.
AB  - OBJECTIVES: To assess the efficacy and cost-effectiveness of pelvic floor muscle
      therapies (PFMT) in women aged > or = 40 years with urodynamic stress
      incontinence (USI) and mixed UI. PATIENTS AND METHODS: In a three-arm randomized
      controlled trial in Leicestershire and Rutland UK, 238 community-dwelling women
      aged > or = 40 years with USI in whom previous primary behavioural intervention
      had failed were randomized to receive either intensive PFMT (79), vaginal cone
      therapy (80) or to continue with primary behavioural intervention (79) for 3
      months. The main outcome measure was the frequency of primary UI episodes, and
      secondary measures were pad-test urine loss, patient perception of problem,
      assessment of PF function, voiding frequency, and pad usage. Validated scales for
      urinary dysfunction, and impact on quality of life and satisfaction were
      collected at an independent interview. RESULTS: All three groups had a moderate
      reduction in UI episodes after intervention but there was no statistically
      significant difference among the groups. There were marginal improvements in
      voiding frequency for all groups, with no statistically significant difference
      among them. CONCLUSIONS: In women who have already had simple behavioural
      therapies (including advice on PFM exercises) for urinary dysfunction, the
      continuation of these behavioural therapies can lead to further improvement. The
      addition of vaginal cone therapy or intensive PFMT does not seem to contribute to
      further improvement. The improvement in pelvic floor function was significantly
      greater in the PFMT arm than in the control arm although this did not translate
      into changes in urinary symptoms.

PMID- 17034606
TI  - Does the clinical efficacy of vardenafil correlate with its effect on the
      endothelial function of cavernosal arteries? A pilot study.
AB  - OBJECTIVE: To investigate whether the results of the ultrasonographic (US)
      measurement of post-occlusive changes in the diameters of cavernosal arteries
      after administering phosphodiesterase type 5 (PDE-5) inhibitor vardenafil could
      be associated with the response to vardenafil in patients with erectile
      dysfunction (ED), as currently there are no reliable methods for predicting the
      success rate of oral PDE-5 inhibitors. PATIENTS AND METHODS: The study included
      122 men with ED; after a complex evaluation, the endothelial function of the
      cavernosal arteries was assessed in all patients before and 1 h after oral
      ingestion of vardenafil (20 mg), using our modification of the US assessment of
      post-occlusive changes in the diameter of cavernosal arteries. After the
      evaluation, all patients received vardenafil 20 mg on demand for 4 weeks. A
      successful response was defined using two endpoints, i.e. the normalization of
      the International Index of Erectile Function Erectile Function domain score (> or
      = 26) and positive answers to both Sexual Encounter Profile questions 2 and 3 on
      > or = 75% of occasions, based on the diary data collected. RESULTS: In all
      patients the mean (sd) initial percentage increase in the cavernosal artery
      diameter (PICAD) in responders and nonresponders was not statistically different,
      at 49 (24) and 43 (26), respectively (P = 0.168), but PICAD values after
      vardenafil were significantly greater in responders, at 73 (16) vs 55 (23) (P <
      0.001). Analysis of data from patients with different causes of ED showed
      statistically significant differences in PICAD between responders and
      nonresponders only in those with arteriogenic ED. The sensitivity and specificity
      of a PICAD of > or = 50% after taking vardenafil 20 mg for predicting a positive
      response to the same dose of the drug in patients with arteriogenic ED were 94.9%
      and 91.3%, respectively. CONCLUSION: The results of the US assessment of post
      occlusive changes in the diameter of cavernosal arteries after vardenafil
      administration are significantly associated with the clinical efficacy of the
      drug in patients with arteriogenic ED.

PMID- 17034607
TI  - Minimally invasive radical cystectomy.

PMID- 17034608
TI  - One week of ciprofloxacin before percutaneous nephrolithotomy significantly
      reduces upper tract infection and urosepsis: a prospective controlled study.
AB  - OBJECTIVE: To evaluate whether 1 week of ciprofloxacin before percutaneous
      nephrolithotomy (PCNL) in patients with stones of > or = 20 mm or pelvicalyceal
      dilatation, reduces urosepsis, as we previously reported that such patients have
      four times the risk of urosepsis after PCNL. PATIENTS AND METHODS: Patients
      undergoing PCNL, and who fulfilled strict selection criteria, were recruited
      prospectively into a study which was conducted in two phases. The study methods
      were similar to those previously described; patients with dilated pelvicalyceal
      systems and/or stones of > or = 20 mm from phase 1 (previously published) acted
      as controls. In the subsequent phase, the same selection criteria applied and
      only those with stones of > or = 20 mm and/or dilated pelvicalyceal systems were
      given ciprofloxacin 250 mg twice daily for 1 week before PCNL and comprised the
      treatment arm. Midstream urine samples, renal pelvic urine and fragmented stones
      were collected to assess culture and sensitivity. Systemic inflammatory response
      syndrome (SIRS) was used to define urosepsis after PCNL. The urologists
      monitoring the patients after PCNL and conducting the analysis were all unaware
      of the characteristics of the stones or intravenous urography findings before
      PCNL. In all, 115 patients (54 in phase 1 and 61 in phase 2) were recruited, of
      whom 46 in phase 1 and 52 in phase 2 had stones of > or = 20 mm and/or a dilated
      pelvicalyceal system, and became the control and treatment arms, respectively.
      RESULTS: The patient demographics were similar in both arms. There was three
      times less risk of upper tract infection (relative risk 3.4, 95% confidence
      interval 1.0-11.8, P = 0.04) and SIRS (2.9, 1.3-6.3, P = 0.004) in the patients
      receiving ciprofloxacin (treatment arm). CONCLUSIONS: The administration of oral
      ciprofloxacin for 1 week before PCNL in patients with stones of > or = 20 mm or
      dilated pelvicalyceal systems significantly reduced the risk of urosepsis.

PMID- 17034609
TI  - Vascular endothelial growth factor-C expression in bladder transitional cell
      cancer and its relationship to lymph node metastasis.
AB  - OBJECTIVE: To elucidate the role of vascular endothelial growth factor-C (VEGF-C)
      in bladder transitional cell carcinoma (TCC), examining VEGF-C expression in
      bladder TCC tissue and the association of VEGF-C with clinicopathological
      features, as the expression of VEGF-C in several carcinomas is significantly
      associated with angiogenesis, lymphangiogenesis and regional lymph node
      metastasis, but there are few reports of VEGF-C expression in bladder TCC.
      PATIENTS AND METHODS: The study included 45 patients with bladder TCC; VEGF-C
      expression was assessed by immunohistochemistry and the association between VEGF
      C expression and angiogenesis, as evaluated by microvessel density (MVD), was
      examined. RESULTS: There was VEGF-C expression in the cytoplasm of tumour cells,
      but very little in the normal transitional epithelium. VEGF-C expression was
      significantly associated with tumour size, pathological T stage, pathological
      grade, lymphatic-venous involvement and pelvic lymph node metastasis (all P <
      0.05). Multivariate analysis showed that VEGF-C expression was an exclusive
      independent factor influencing pelvic lymph node metastasis. Moreover, the
      patients with high VEGF-C expression had a markedly poorer prognosis than those
      with no or low VEGF-C expression (P = 0.014). A multivariate analysis based on
      the Cox proportional hazard model showed that lymph node metastasis was only an
      independent prognostic factor in the multivariate analysis using the Cox
      regression model (P = 0.010). CONCLUSION: The present study provides evidence
      supporting the involvement of VEGF-C expression in the promotion of lymph node
      metastasis in bladder TCC. Examination of VEGF-C expression in biopsy specimens
      might be beneficial in predicting pelvic lymph node metastasis.

PMID- 17034610
TI  - Heat-shock protein 25 ameliorates calcium oxalate crystal-mediated oxidative
      stress in renal epithelial cells.
AB  - OBJECTIVE: To investigate whether the antioxidant protection attributed to small
      heat-shock proteins (sHSPs) affects calcium oxalate stone formation, a pro
      oxidant disease. MATERIALS AND METHODS: Canine distal tubular epithelial cells
      (Madin-Darby canine kidney, MDCK cells) were grown as confluent monolayers.
      Treatment regimens included control and HS-treated cells (37 degrees C and 42
      degrees C for 1 h) with or without calcium oxalate monohydrate (COM) or free
      oxalate treatment (28 microg/cm2) 16 h later. In digitonin-permeabilized cells,
      O2- was measured by lucigenin-enhanced chemiluminescence over a 5-min period, to
      measure mitochondrial O2- production. Protein expression was assessed by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis Western blot analysis using
      specific antibodies. RESULTS: COM significantly increased O2- production in MDCK
      cells. HS treatment, which up-regulated HSP25 expression, significantly decreased
      this O2- production (P < 0.05) but had no effect in control cells. In COM-treated
      cells (20 h) there was a marked and significant down-regulation of both HSP 25,
      HSP 70 and heme oxygenase-1 expression compared to cells treated with HS alone (P
      < 0.05). Free oxalate had no effect on HSP 25 expression. CONCLUSIONS: The
      results suggest that the COM-induced increase in mitochondrial O2- production in
      MDCK cells is ameliorated by HSP 25 up-regulation via HS. Specific COM inhibition
      of HSP 25, HSP 70 and heme oxygenase-1 up-regulation suggests that COM-induced
      reactive oxygen species damage is unable to benefit from HSP-associated
      physiological resistance.

PMID- 17034611
TI  - Challenges in a larger bladder replacement with cell-seeded and unseeded small
      intestinal submucosa grafts in a subtotal cystectomy model.
AB  - OBJECTIVE: To evaluate small intestinal submucosa (SIS), unseeded or seeded, as a
      possible augmentation material in a canine model of subtotal cystectomy.
      MATERIALS AND METHODS: In all, 22 male dogs had a 90% partial cystectomy and were
      then divided into three groups. At 1 month after the initial cystectomy, dogs in
      group 1 (unseeded, six) and group 2 (seeded, six) received a bladder augmentation
      with a corresponding SIS graft. The dogs in group 3 (ten) received no further
      surgery and were considered the surgical control group. All dogs were evaluated
      before and after surgery with blood chemistry, urine culture, intravenous
      urography, cystograms and cystometrograms. After surgery (at 1, 5 and 9 months),
      the bladders were examined using routine histology and immunohistochemistry.
      RESULTS: All 22 dogs survived the subtotal cystectomy, and 18 survived their
      intended survival period. One dog, in group 2 (seeded), was killed at 1 month
      after augmentation due to bladder perforation caused by a large piece of
      incompletely absorbed SIS. Three other dogs (group 1, two; and group 2, one) were
      killed within 2 months after augmentation due to bladder obstruction by stones.
      Group 1 and group 2 SIS grafts had moderate to heavy adhesion, graft shrinkage,
      and some had bone and calcification at the graft site. Histologically, there was
      limited bladder regeneration in both groups. Interestingly, dogs in group 3 at 1
      month after cystectomy (when group 1 and 2 received their augmentations) had
      severely shrunken bladders and histologically had severe inflammation, fibroblast
      infiltration and muscle hypertrophy. These results verify the subtotal cystectomy
      model. CONCLUSIONS: The use of seeded or unseeded SIS in a subtotal cystectomy
      model does not induce the same quality and quantity of bladder regeneration that
      is seen in the 40% non-inflammatory cystectomy model. This study provides
      important insights into the process of regeneration in a severely damaged
      bladder. The results led us to re-evaluate the critical elements required for a
      complete bladder replacement using tissue-engineering techniques.

PMID- 17034612
TI  - Pygeum africanum extract inhibits proliferation of human cultured prostatic
      fibroblasts and myofibroblasts.
AB  - OBJECTIVE: To investigate the effect of Pygeum africanum (PA) extract on the
      proliferation of cultured human prostatic myofibroblasts and fibroblasts; this
      extract is used for treating urinary disorders associated with benign prostatic
      hyperplasia (BPH). MATERIALS AND METHODS: Primary cultures of prostatic stromal
      cells were obtained from histologically confirmed human BPH by enzymatic
      digestion. Cell proliferation was measured by 5-bromo2'-deoxy-uridine (BrdU)
      incorporation assays, and cytotoxicity by luminescent quantification of adenylate
      kinase activity. RESULTS: Cultured cells were labelled by an anti-vimentin
      antibody, and most of them by an alpha-smooth-muscle-actin antibody, revealing
      the presence of fibroblasts and myofibroblasts. BrdU incorporation tests showed
      that proliferation of cultured human stromal cells, stimulated by fetal calf
      serum, by basic fibroblast growth factor and by epidermal growth factor, was dose
      dependently inhibited by PA extract (5-100 microg/mL). Except at 100 microg/mL,
      no acute cytotoxicity of the extract was detected after 24 h of culture.
      Similarly, the extract dose-dependently inhibited the proliferation of Madin
      Darby canine kidney epithelial cells, but to a lesser extent; whatever the dose
      of extract, no acute toxicity was evident on this cell line. CONCLUSION: PA
      extract inhibits the proliferation of cultured human prostatic myofibroblasts and
      fibroblasts. We propose that cultured human prostatic cells offer a reliable
      model for preclinical screening of therapeutic agents, and to study the
      mechanisms underlying the inhibition of proliferation.

PMID- 17034613
TI  - Effects of ovariectomy and oestrogen replacement on the function and expression
      of Rho-kinase in rat bladder smooth muscle.
AB  - OBJECTIVE: To investigate the effects of ovariectomy and oestrogen replacement on
      the function and expression of Rho-kinase in rat bladder smooth muscle, as the
      actual effects of oestrogen deprivation on bladder smooth muscle are unclear.
      MATERIALS AND METHODS: Female Sprague-Dawley rats were placed into one of three
      groups: sham-operated, bilateral ovariectomy-only, and bilateral ovariectomy plus
      oestrogen replacement groups. In the last group, oestrogen was replaced by weekly
      injection of beta-estradiol 17-cypionate (250 microg/kg subcutaneously for 6
      weeks) beginning at 1 week after ovariectomy, whereas the other groups received
      vehicle-only injections for 6 weeks. After treatment, the bladder was removed for
      muscle strip studies to evaluate the effects of Y-27632, a specific inhibitor of
      Rho-kinase, on baseline tension and carbachol-induced tonic contractions. Also,
      the protein expression of RhoA and Rho-kinase isoenzymes was assessed by Western
      blot analysis. RESULTS: Of the three groups, incubation with 10 microm Y-27632
      resulted in the largest decrease in baseline tension of strips from the bilateral
      ovariectomy-only group, but this was not statistically significant (P > 0.05).
      For carbachol-induced tonic contractions, strips from the bilateral ovariectomy
      only group were attenuated the most among the three groups after adding Y-27632
      (P < 0.05). However, there were no significant differences in the levels of RhoA
      and the two Rho-kinase isoenzymes in bladder tissues from the three groups.
      CONCLUSION: Our data show that oestrogen might inhibit the function of Rho-kinase
      in bladder smooth muscle, while having no significant effect on its expression.
      This finding might help to explain the greater incidence of urinary tract
      symptoms suggestive of overactive bladder after the menopause in women.

PMID- 17034614
TI  - Have the wheels come off the Asian-Pacific revolution?

PMID- 17034615
TI  - Laparoscopic live-donor nephrectomy.

PMID- 17034616
TI  - Using routine data to define clinical case-mix and compare hospital outcomes in
      urology.

PMID- 17034617
TI  - BJU international is really international.

PMID- 17034618
TI  - Idiopathic retroperitoneal fibrosis: the case for nonsurgical treatment.

PMID- 17034619
TI  - Nurse-led flexible cystoscopy: experience from one UK centre.

PMID- 17034620
TI  - Hypoandrogen-metabolic syndrome: a significant issue for men's health.

PMID- 17034621
TI  - Surgical atlas. A continent cutaneous ileal neobladder using the serous-lined
      extramural valves.

PMID- 17034622
TI  - N-terminal region of Saccharomyces cerevisiae eRF3 is essential for the
      functioning of the eRF1/eRF3 complex beyond translation termination.
AB  - BACKGROUND: Termination of translation in eukaryotes requires two release
      factors, eRF1, which recognizes all three nonsense codons and facilitates release
      of the nascent polypeptide chain, and eRF3 stimulating translation termination in
      a GTP-depended manner. eRF3 from different organisms possess a highly
      conservative C region (eRF3C), which is responsible for the function in
      translation termination, and almost always contain the N-terminal extension,
      which is inessential and vary both in structure and length. In the yeast
      Saccharomyces cerevisiae the N-terminal region of eRF3 is responsible for
      conversion of this protein into the aggregated and functionally inactive prion
      form. RESULTS: Here, we examined functional importance of the N-terminal region
      of a non-prion form of yeast eRF3. The screen for mutations which are lethal in
      combination with the SUP35-C allele encoding eRF3C revealed the sup45 mutations
      which alter the N-terminal domain of eRF1 and increase nonsense codon
      readthrough. However, further analysis showed that synthetic lethality was not
      caused by the increased levels of nonsense codon readthrough. Dominant mutations
      in SUP35-C were obtained and characterized, which remove its synthetic lethality
      with the identified sup45 mutations, thus indicating that synthetic lethality was
      not due to a disruption of interaction with proteins that bind to this eRF3
      region. CONCLUSION: These and other data demonstrate that the N-terminal region
      of eRF3 is involved both in modulation of the efficiency of translation
      termination and functioning of the eRF1/eRF3 complex outside of translation
      termination.

PMID- 17034623
TI  - A relationship between oxytocin and anxiety of romantic attachment.
AB  - The formation of social bonding is fundamental for several animals, including
      humans, for its relevant and obvious impact upon reproduction and, thus, survival
      of the species. Recent data would suggest that oxytocin might be one of the
      mediators of this process. Given the paucity of data on the possible involvement
      of oxytocin in human attachment, the present study was aimed to explore the
      possible relationships between the plasma levels of this neuropeptide and
      romantic attachment in healthy subjects. Forty-five healthy subjects who
      volunteered for the study, were included in the study. The romantic attachment
      was assessed using the Italian version of the so-called "Experiences in Close
      Relationships" (ECR), a self-report questionnaire for measuring this parameter in
      adults. The results showed that attachment anxiety and oxytocin are positively
      linked in romantic attachment to a statistically significant degree (r = 0.30, p
      = 0.04), that is, the higher the oxytocin levels the higher the score on the
      anxiety scale of the ECR. The authors suggest the hypothesis that this link
      represents one of the biological processes resulting in those rewarding emotions
      related to romantic attachment.

PMID- 17034624
TI  - Determination of the genetic structure of remnant Morus boninensis Koidz. trees
      to establish a conservation program on the Bonin Islands, Japan.
AB  - BACKGROUND: Morus boninensis, is an endemic plant of the Bonin (Ogasawara)
      Islands of Japan and is categorized as "critically endangered" in the Japanese
      red data book. However, little information is available about its ecological,
      evolutionary and genetic status, despite the urgent need for guidelines for the
      conservation of the species. Therefore, we adopted Moritz's MU concept, based on
      the species' current genetic structure, to define management units and to select
      mother tree candidates for seed orchards. RESULTS: Nearly all individuals of the
      species were genotyped on the basis of seven microsatellite markers. Genetic
      diversity levels in putative natural populations were higher than in putative man
      made populations with the exception of those on Otouto-jima Island. This is
      because a limited number of maternal trees are likely to have been used for seed
      collection to establish the man-made populations. A model-based clustering
      analysis clearly distinguished individuals into nine clusters, with a large
      difference in genetic composition between the population on Otouto-jima Island,
      the putative natural populations and the putative man-made populations. The
      Otouto-jima population appeared to be genetically differentiated from the others;
      a finding that was also supported by pairwise FST and RST analysis. Although
      multiple clusters were detected in the putative man-made populations, the pattern
      of genetic diversity was monotonous in comparison to the natural populations.
      CONCLUSION: The genotyping by microsatellite markers revealed strong genetic
      structures. Typically, artificial propagation of this species has ignored the
      genetic structure, relying only on seeds from Otouto-jima for replanting on other
      islands, because of a problem with inter-specific hybridization on Chichi-jima
      and Haha-jima Islands. However, this study demonstrates that we should be taking
      into consideration the genetic structure of the species when designing a
      propagation program for the conservation of this species.

PMID- 17034625
TI  - Cross-sectional survey of older peoples' views related to influenza vaccine
      uptake.
AB  - BACKGROUND: The population's views concerning influenza vaccine are important in
      maintaining high uptake of a vaccine that is required yearly to be effective.
      Little is also known about the views of the more vulnerable older population over
      the age of 74 years. METHODS: A cross-sectional survey of community dwelling
      people aged 75 years and over wh, previous participant was conducted using a
      postal questionnaire. Responses were analysed by vaccine uptake records and by
      socio-demographic and medical factors. RESULTS: 85% of men and 75% of women were
      vaccinated against influenza in the previous year. Over 80% reported being
      influenced by a recommendation by a health care worker. The most common reason
      reported for non uptake was good health (44%), or illness considered to be due to
      the vaccine (25%). An exploration of the crude associations with socio-economic
      status suggested there may be some differences in the population with these two
      main reasons. 81% of people reporting good health lived in owner occupied housing
      with central heating vs. 63% who did not state this as a reason (p = 0.04),
      whereas people reporting ill health due to the vaccine was associated with poorer
      social circumstances. 11% lived in the least deprived neighbourhood compared to
      36% who did not state this as a reason (p = 0.05) and were less likely to be
      currently married than those who did not state this as a reason (25% vs 48% p =
      0.05). CONCLUSION: Vaccine uptake was high, but non uptake was still noted in 1
      in 4 women and 1 in 7 men aged over 74 years. Around 70% reported they would not
      have the vaccine in the following year. The divergent reasons for non-uptake, and
      the positive influence from a health care worker, suggests further uptake will
      require education and encouragement from a health care worker tailored towards
      the different views for not having influenza vaccination. Non-uptake of influenza
      vaccine because people viewed themselves as in good health may explain the modest
      socio-economic differentials in influenza vaccine uptake in elderly people noted
      elsewhere. Reporting of ill-health due to the vaccine may be associated with a
      different, poorer background.

PMID- 17034626
TI  - Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1.
AB  - BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's
      syndrome, plays a role in axon outgrowth and branching but also in epithelial
      morphogenesis. The molecular mechanism of its action is, however, widely unknown.
      Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a
      whey acidic protein (WAP) domain homologous to some serine protease inhibitors,
      and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1
      (DmKal-1) has the same protein structure with minor differences, the most
      important of which is the presence of only two FnIII repeats and a C-terminal
      region showing a low similarity with the third and the fourth human FnIII
      repeats. We present a structure-function analysis of the different DmKal-1
      domains, including a predicted heparan-sulfate binding site. RESULTS: This study
      was performed overexpressing wild type DmKal-1 and a series of deletion and point
      mutation proteins in two different tissues: the cephalopharyngeal skeleton of the
      embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal
      skeleton induced dosage-sensitive structural defects, and we used these
      phenotypes to perform a structure-function dissection of the protein domains. The
      reproduction of two deletions found in Kallmann's Syndrome patients determined a
      complete loss of function, whereas point mutations induced only minor alterations
      in the activity of the protein. Overexpression of the mutant proteins in the wing
      disc reveals that the functional relevance of the different DmKal-1 domains is
      dependent on the extracellular context. CONCLUSION: We suggest that the role
      played by the various protein domains differs in different extracellular
      contexts. This might explain why the same mutation analyzed in different tissues
      or in different cell culture lines often gives opposite phenotypes. These
      analyses also suggest that the FnIII repeats have a main and specific role, while
      the WAP domain might have only a modulator role, strictly connected to that of
      the fibronectins.

PMID- 17034627
TI  - Tumour risk associated with use of cellular telephones or cordless desktop
      telephones.
AB  - BACKGROUND: The use of cellular and cordless telephones has increased
      dramatically during the last decade. There is concern of health problems such as
      malignant diseases due to microwave exposure during the use of these devices. The
      brain is the main target organ. METHODS: Since the second part of the 1990's we
      have performed six case-control studies on this topic encompassing use of both
      cellular and cordless phones as well as other exposures. Three of the studies
      concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma
      (NHL) and one testicular cancer. Exposure was assessed by self-administered
      questionnaires. RESULTS: Regarding acoustic neuroma analogue cellular phones
      yielded odds ratio (OR) = 2.9, 95 % confidence interval (CI) = 2.0-4.3, digital
      cellular phones OR = 1.5, 95 % CI = 1.1-2.1 and cordless phones OR = 1.5, 95 % CI
      = 1.04-2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7,
      95 % CI = 1.3-2.3; OR = 1.5, 95 % CI = 1.2-1.9 and OR = 1.5, 95 % CI = 1.1-1.9,
      respectively. The ORs increased with latency period with highest estimates using
      > 10 years time period from first use of these phone types. Lower ORs were
      calculated for astrocytoma grade I-II. No association was found with salivary
      gland tumours, NHL or testicular cancer although an association with NHL of T
      cell type could not be ruled out. CONCLUSION: We found for all studied phone
      types an increased risk for brain tumours, mainly acoustic neuroma and malignant
      brain tumours. OR increased with latency period, especially for astrocytoma grade
      III-IV. No consistent pattern of an increased risk was found for salivary gland
      tumours, NHL, or testicular cancer.

PMID- 17034628
TI  - Understanding and meeting the needs of those using growth hormone injection
      devices.
AB  - BACKGROUND: Recombinant human growth hormone (r-hGH) is used to treat: growth
      hormone deficiency in children and adults; children born small for gestational
      age; Turner's syndrome; and chronic renal failure. r-hGH is administered by daily
      subcutaneous injection and may be given using a number of different
      administration devices. The aim of this survey was, firstly, to identify which
      attributes of an r-hGH administration device are considered most important to
      physicians, teenage patients, parents of young children requiring GH and nurses
      who have experience of r-hGH administration, and, secondly, to determine how they
      rate existing devices in each of these key attributes. METHODS: The opinions of
      67 individuals with experience in r-hGH administration were captured in
      discussion sessions. Parents, physicians and nurses were asked to rate 19 device
      attributes by completing a questionnaire, and to rank four different r-hGH
      administration devices (including a conceptual electronic device) in order of
      preference. RESULTS: Reliability, ease of use, lack of pain during injection,
      safety in use, storage, and number of steps in preparation before use, during use
      and after were considered to be the five most desirable attributes of an r-hGH
      administration device. An electronic device was preferred to an automatic, multi
      dose injection device, a needle-free injection device or a manual, ready-to-use,
      disposable injection device. CONCLUSION: In the opinion of physicians, nurses and
      parents using r-hGH injection devices, an ideal device must combine reliability
      with simplicity, while delivering treatment with minimal pain. An electronic
      device, which combines many of the most useful features of existing devices with
      novel functions, was the preferred option for r-hGH administration.

PMID- 17034629
TI  - Langerhans cell histiocytosis on the penis: a case report.
AB  - BACKGROUND: Langerhans cell histiocytosis affects mainly young children and
      features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin,
      and other organs. A few cases of Langerhans cell histiocytosis on the penis have
      been reported in the literature. We present a case of Langerhans cell
      histiocytosis on the penis and review the similar cases in the literature. CASE
      PRESENTATION: The patient was a 13-year-old boy who had a history of lymph node,
      femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis
      who noticed a painful nodule on the prepuce of his penis. The histological and
      immunohistochemical examination fulfilled the criteria of Langerhans cell
      histiocytosis. CONCLUSION: We herein describe the case reported of Langerhans
      cell histiocytosis on the penis.

PMID- 17034630
TI  - Bilateral ischemic optic neuropathy after transurethral prostatic resection: a
      case report.
AB  - BACKGROUND: Nonarteritic ischemic optic neuropathy affects the anterior portion
      of the optic nerve and is characterized by sudden, painless visual loss. The
      affected eye has a relative afferent pupillary defect. The typical funduscopic
      appearance includes optic disc edema, with associated nerve fiber layer
      hemorrhage. Risk factors include advanced age, systemic hypertension, nocturnal
      hypotension, diabetes mellitus, and a small cup-to-disc ratio. Bilateral
      presentation is rare. Postoperative optic neuropathy has been associated with
      nonocular surgery; risk factors include a combination of prolonged surgical
      times, acute systemic hypotension, anemia due to blood loss, or prone
      positioning. We report for the first time a patient with bilateral, simultaneous
      anterior ischemic optic neuropathy after elective transurethral prostatic
      resection. CASE PRESENTATION: A 66-year old man underwent surgery for benign
      prostatic hyperplasia. The preoperative blood pressure was 140/85 mmHg,
      hemoglobin 15.9 g/dL, and hematocrit 48.6%. Two hours postoperatively, the blood
      pressure, hemoglobin, and hematocrit dropped dramatically. One day later,
      transient horizontal diplopia developed. Funduscopy showed a congenitally small
      cup-to-disc ratio without papillary edema. Other ocular findings were
      unremarkable. By 4 days postoperatively, sudden and painless amaurosis
      bilaterally developed when the patient awoke with nausea and vomiting. Visual
      acuity was no light perception bilaterally. The optic discs were swollen with
      small hemorrhages. Scans of the head and orbits and electrolyte levels were
      normal. There were no responses on visual evoked potentials bilaterally. The
      blood pressure was 90/50 mm Hg, the hemoglobin 7.0 g/dL, and the hematocrit
      22.9%, necessitating infusion of three units of packed red blood cells. The blood
      pressure, hematocrit, and hemoglobin increased to normal levels. Three months
      later the visual acuity remained no light perception. The pupils were unreactive
      and there was marked optic disc atrophy bilaterally. CONCLUSION: Bilateral and
      simultaneous acute ischemic optic neuropathy may be a rare but devastating
      surgical complication. The combination of anemia and hypotension may increase the
      risk of anterior ischemic optic neuropathy postoperatively after transurethral
      prostatic resection.

PMID- 17034631
TI  - Spontaneous intra-peritoneal bleeding secondary to warfarin, presenting as an
      acute appendicitis: a case report and review of literature.
AB  - BACKGROUND: Warfarin is a coumarin anti-coagulant, used widely for the
      therapeutic and prophylactic anticoagulation. Although, it is considered as a
      life saving medicine, it is associated with the significant adverse effects
      including intra-abdominal bleeding, which have been very well documented in
      literature. However, the presentation of warfarin induced intra-peritoneal
      bleeding as an acute appendicitis has not been reported in English literature. We
      report this rare, spontaneous intra-peritoneal bleeding secondary to warfarin
      therapy, mimicking the signs and symptoms of an acute appendicitis for the first
      time in English literature. CASE PRESENTATION: A 41 year-old female patient who
      was on warfarin for prophylaxis following the previous episode of pulmonary
      embolism, presented to the Casualty with the typical symptoms of an acute
      appendicitis. During operative intervention, we found it to be the spontaneous
      intra-peritoneal bleeding secondary to warfarin. The patient recovered well
      following the operation. CONCLUSION: We recommend the use of the radiological
      investigations in all the cases of acute abdomen who are on warfarin even if the
      INR is within the therapeutic range.

PMID- 17034633
TI  - Guidance for industry: patient-reported outcome measures: use in medical product
      development to support labeling claims: draft guidance.
AB  - This guidance describes how the FDA evaluates patient-reported outcome (PRO)
      instruments used as effectiveness endpoints in clinical trials. It also describes
      our current thinking on how sponsors can develop and use study results measured
      by PRO instruments to support claims in approved product labeling (see appendix
      point 1). It does not address the use of PRO instruments for purposes beyond
      evaluation of claims made about a drug or medical product in its labeling. By
      explicitly addressing the review issues identified in this guidance, sponsors can
      increase the efficiency of their endpoint discussions with the FDA during the
      product development process, streamline the FDA's review of PRO endpoint
      adequacy, and provide optimal information about the patient's perspective of
      treatment benefit at the time of product approval. A PRO is a measurement of any
      aspect of a patient's health status that comes directly from the patient (i.e.,
      without the interpretation of the patient's responses by a physician or anyone
      else). In clinical trials, a PRO instrument can be used to measure the impact of
      an intervention on one or more aspects of patients' health status, hereafter
      referred to as PRO concepts, ranging from the purely symptomatic (response of a
      headache) to more complex concepts (e.g., ability to carry out activities of
      daily living), to extremely complex concepts such as quality of life, which is
      widely understood to be a multidomain concept with physical, psychological, and
      social components. Data generated by a PRO instrument can provide evidence of a
      treatment benefit from the patient perspective. For this data to be meaningful,
      however, there should be evidence that the PRO instrument effectively measures
      the particular concept that is studied. Generally, findings measured by PRO
      instruments may be used to support claims in approved product labeling if the
      claims are derived from adequate and well-controlled investigations that use PRO
      instruments that reliably and validly measure the specific concepts at issue. The
      glossary defines many of the terms used in this guidance. In particular, the term
      instrument refers to the actual questions or items contained in a questionnaire
      or interview schedule along with all the additional information and documentation
      that supports the use of these items in producing a PRO measure (e.g.,
      interviewer training and instructions, scoring and interpretation manual). The
      term conceptual framework refers to how items are grouped according to
      subconcepts or domains (e.g., the item walking without help may be grouped with
      another item, walking with difficulty, within the domain of ambulation, and
      ambulation may be further grouped into the concept of physical ability). FDA's
      guidance documents, including this guidance, do not establish legally enforceable
      responsibilities. Instead, guidance documents describe the Agency's current
      thinking on a topic and should be viewed only as recommendations, unless specific
      regulatory or statutory requirements are cited. The use of the word should in
      Agency guidance documents means that something is suggested or recommended but
      not required. First publication of the Draft Guidance by the Food and Drug
      Administration--February 2006.

PMID- 17034634
TI  - Simultaneous alcohol and cannabis expectancies predict simultaneous use.
AB  - BACKGROUND: Simultaneous use of alcohol and cannabis predicts increased negative
      consequences for users beyond individual or even concurrent use of the two drugs.
      Given the widespread use of the drugs and common simultaneous consumption,
      problems unique to simultaneous use may bear important implications for many
      substance users. Cognitive expectancies offer a template for future drug use
      behavior based on previous drug experiences, accurately predicting future use and
      problems. Studies reveal similar mechanisms underlying both alcohol and cannabis
      expectancies, but little research examines simultaneous expectancies for alcohol
      and cannabis use. Whereas research has demonstrated unique outcomes associated
      with simultaneous alcohol and cannabis use, this study hypothesized that unique
      cognitive expectancies may underlie simultaneous alcohol and cannabis use.
      RESULTS: This study examined a sample of 2600 (66% male; 34% female) Internet
      survey respondents solicited through advertisements with online cannabis-related
      organizations. The study employed known measures of drug use and expectancies, as
      well as a new measure of simultaneous drug use expectancies. Expectancies for
      simultaneous use of alcohol and cannabis predicted simultaneous use over and
      above expectancies for each drug individually. DISCUSSION: Simultaneous
      expectancies may provide meaningful information not available with individual
      drug expectancies. These findings bear potential implications on the assessment
      and treatment of substance abuse problems, as well as researcher
      conceptualizations of drug expectancies. Policies directing the treatment of
      substance abuse and its funding ought to give unique consideration to
      simultaneous drug use and its cognitive underlying factors.

PMID- 17034632
TI  - Acute ischemic heart disease and interventional cardiology: a time for pause.
AB  - BACKGROUND: A major change has occurred in the last few years in the therapeutic
      approach to patients presenting with all forms of acute coronary syndromes.
      Whether or not these patients present initially to tertiary cardiac care centers,
      they are now routinely referred for early coronary angiography and increasingly
      undergo percutaneous revascularization. This practice is driven primarily by the
      angiographic image and technical feasibility. Concomitantly, there has been a
      decline in expectant or ischemia-guided medical management based on specific
      clinical presentation, response to initial treatment, and results of noninvasive
      stratification. This 'tertiarization' of acute coronary care has been fueled by
      the increasing sophistication of the cardiac armamentarium, the peer-reviewed
      publication of clinical studies purporting to show the superiority of invasive
      cardiac interventions, and predominantly supporting (non-peer-reviewed)
      editorials, newsletters, and opinion pieces. DISCUSSION: This review presents
      another perspective, based on a critical reexamination of the evidence. The
      topics addressed are: reperfusion treatment of ST-elevation myocardial
      infarction; the indications for invasive intervention following thrombolysis; the
      role of invasive management in non-ST-elevation myocardial infarction and
      unstable angina; and cost-effectiveness and real world considerations. A few
      cases encountered in recent practice in community and tertiary hospitals are
      presented for illustrative purposes The numerous and far-reaching scientific,
      economic, and philosophical implications that are a consequence of this marked
      change in clinical practice as well as healthcare, decisional and conflict of
      interest issues are explored. SUMMARY: The weight of evidence does not support
      the contemporary unfocused broad use of invasive interventional procedures across
      the spectrum of acute coronary clinical presentations. Excessive and unselective
      recourse to these procedures has deleterious implications for the organization of
      cardiac health care and undesirable economic, scientific and intellectual
      consequences. It is suggested that there is need for a new equilibrium based on
      more refined clinical risk stratification in the treatment of patients who
      present with acute coronary syndromes.

PMID- 17034635
TI  - A web-based system for tissue microarray data management.
AB  - BACKGROUND: Tissue Microarray is a novel technique for analysing large amounts of
      immunohistochemically stained specimens. However, those large amounts make it
      difficult to design, prepare and analyze a tissue microarray, so that software
      support is almost inevitable. METHODS: We designed a tissue microarray data
      management system starting from specifications obtained by pathologists, and
      arranged for a preliminary validation in thyroid pathology. RESULTS: A web-based
      system has been developed, basing on open-source software and principles, that
      was well accepted by pathologists and allowed to carry out a study on 52 thyroid
      pathology cases. CONCLUSION: Though limited in functionalities, the developed
      system is effective and can be downloaded at the address
      http://mitel.dimi.uniud.it/timan/.

PMID- 17034636
TI  - Harm reduction services for British Columbia's First Nation population: a
      qualitative inquiry into opportunities and barriers for injection drug users.
AB  - BACKGROUND: Aboriginal injection drug users are the fastest growing group of new
      Human Immunodeficiency Virus cases in Canada. However, there remains a lack of
      comprehensive harm reduction services available to First Nation persons,
      particularly for First Nation people dwelling in rural and reserve communities.
      This paper reports findings from an exploratory study of current harm reduction
      practices in First Nation communities. The purpose of this study was to provide
      an overview of the availability and content of current harm reduction practices,
      as well as to identify barriers and opportunities for implementing these services
      in First Nation communities. METHODS: Key informant interviews were conducted
      with 13 addictions service providers from the province of British Columbia,
      Canada. RESULTS: Participants identified barriers to these services such as
      community size and limited service infrastructure, lack of financial resources,
      attitudes towards harm reduction services and cultural differences. CONCLUSION:
      It was recommended that community education efforts be directed broadly within
      the community before establishing harm reduction services and that the readiness
      of communities be assessed.

PMID- 17034637
TI  - Dynamics of immune response and drug resistance in malaria infection.
AB  - BACKGROUND: Malaria parasites that concurrently infect a host compete on the
      basis of their intrinsic growth rates and by stimulating cross-reactive immune
      responses that inhibit each others' growth. If the phenotypes also show different
      drug sensitivities ('sensitive' vs. 'resistant' strains), drug treatment can
      change their joint dynamics and the long-term outcome of the infection: most
      obviously, persistent drug pressure can permit the more resistant, but otherwise
      competitively-inferior, strains to dominate. METHODS: Here a mathematical model
      is developed to analyse how these and more subtle effects of antimalarial drug
      use are modulated by immune response, repeated re-inoculation of parasites, drug
      pharmacokinetic parameters, dose and treatment frequency. RESULTS: The model
      quantifies possible effects of single and multiple (periodic) treatment on the
      outcome of parasite competition. In the absence of further inoculation, the
      dosage and/or treatment frequency required for complete clearance can be
      estimated. With persistent superinfection, time-average parasite densities can be
      derived in terms of the basic immune-regulating parameters, the drug efficacy and
      treatment regimen. CONCLUSION: The functional relations in the model are
      applicable to a wide range of conditions and transmission environments, allowing
      predictions to be made on both the individual and the community levels, and, in
      particular, transitions from drug-sensitive to drug-resistant parasite dominance
      to be projected on both levels.

PMID- 17034638
TI  - An overabundance of phase 0 introns immediately after the start codon in
      eukaryotic genes.
AB  - BACKGROUND: A knowledge of the positions of introns in eukaryotic genes is
      important for understanding the evolution of introns. Despite this, there has
      been relatively little focus on the distribution of intron positions in genes.
      RESULTS: In proteins with signal peptides, there is an overabundance of phase 1
      introns around the region of the signal peptide cleavage site. This has been
      described before. But in proteins without signal peptides, a novel phenomenon is
      observed: There is a sharp peak of phase 0 intron positions immediately following
      the start codon, i.e. between codons 1 and 2. This effect is seen in a wide range
      of eukaryotes: Vertebrates, arthropods, fungi, and flowering plants. Proteins
      carrying this start codon intron are found to comprise a special class of
      relatively short, lysine-rich and conserved proteins with an overrepresentation
      of ribosomal proteins. In addition, there is a peak of phase 0 introns at
      position 5 in Drosophila genes with signal peptides, predominantly representing
      cuticle proteins. CONCLUSION: There is an overabundance of phase 0 introns
      immediately after the start codon in eukaryotic genes, which has been described
      before only for human ribosomal proteins. We give a detailed description of these
      start codon introns and the proteins that contain them.

PMID- 17034639
TI  - Role of TNFalpha in pulmonary pathophysiology.
AB  - Tumor necrosis factor alpha (TNFalpha) is the most widely studied pleiotropic
      cytokine of the TNF superfamily. In pathophysiological conditions, generation of
      TNFalpha at high levels leads to the development of inflammatory responses that
      are hallmarks of many diseases. Of the various pulmonary diseases, TNFalpha is
      implicated in asthma, chronic bronchitis (CB), chronic obstructive pulmonary
      disease (COPD), acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS). In addition to its underlying role in the inflammatory events, there is
      increasing evidence for involvement of TNFalpha in the cytotoxicity. Thus,
      pharmacological agents that can either suppress the production of TNFalpha or
      block its biological actions may have potential therapeutic value against a wide
      variety of diseases. Despite some immunological side effects, anti-TNFalpha
      therapeutic strategies represent an important breakthrough in the treatment of
      inflammatory diseases and may have a role in pulmonary diseases characterized by
      inflammation and cell death.

PMID- 17034640
TI  - Patient-reported outcomes in a trial of exenatide and insulin glargine for the
      treatment of type 2 diabetes.
AB  - BACKGROUND: Patient-reported measures can be used to examine whether drug
      differences other than clinical efficacy have an impact on outcomes that may be
      important to patients. Although exenatide and insulin glargine appear to have
      similar efficacy for treatment of type 2 diabetes, there are several differences
      between the two treatments that could influence outcomes from the patient's
      perspective. The purpose of the current study was to examine whether the two
      drugs were comparable as assessed by patient-reported outcomes using data from a
      clinical trial in which these injectable medications were added to pre-existing
      oral treatment regimens. METHODS: Patients were randomized to either twice daily
      exenatide or once daily insulin glargine during a 26-week international trial. At
      baseline and endpoint, five patient-reported outcome measures were administered:
      the Vitality Scale of the SF-36, The Diabetes Symptom Checklist - Revised (DSC
      R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes
      Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was
      analyzed within each treatment group. Group differences were examined with
      General linear models (GLMs), controlling for country and baseline scores.
      RESULTS: A total of 549 patients with type 2 diabetes were enrolled in the trial,
      and current analyses were conducted with data from the 455 per protocol patients
      (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian
      (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5
      years. Paired t-tests found that both treatment groups demonstrated statistically
      significant baseline to endpoint change on several of the health outcomes
      instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs
      found no statistically significant differences between groups in change on the
      health outcomes instruments. CONCLUSION: This analysis found that both exenatide
      and insulin glargine were associated with significant improvements in patient
      reported outcomes when added to oral medications among patients with type 2
      diabetes. Despite an additional daily injection and a higher rate of
      gastrointestinal adverse events, treatment satisfaction in the exenatide group
      was comparable to that of the glargine group, possibly because of weight
      reduction observed in patients treated with exenatide.

PMID- 17034641
TI  - Development of a Health-Related Quality of Life Questionnaire (HRQL) for patients
      with Extremity Soft Tissue Infections (ESTI).
AB  - BACKGROUND: Past clinical trials of antimicrobial treatment in soft tissue
      infections have focused on non-standardized clinical and physiological outcome
      variables, and have not considered the subjective experience of patients. The
      objective of this study was to develop a health-related quality of life
      questionnaire (HRQL) for patients with extremity soft tissue infections (ESTI)
      for future use in clinical trials. METHODS: The design of this study followed
      published guidelines and included item generation, item reduction, and
      questionnaire preparation. Study subjects were consenting English-speaking adults
      with acute ESTI requiring prescription of at least two days of outpatient
      intravenous antibiotic therapy. RESULTS: A list of 49 items that adversely impact
      the quality of life of patients with ESTI was generated by literature review,
      informal health professional feedback, and semi-structured interviews with twenty
      patients. A listing of these items was then administered to 95 patients to
      determine their relative importance on quality of life. A questionnaire was
      prepared that included the twenty most important items with a 5-point Likert
      scale response. Questionnaire domains included physical symptoms, problems
      performing their activities of daily living, impairment of their emotional
      functioning, and difficulties in their social interactions as related to their
      ESTI. The final questionnaire was pre-tested on a further ten patients and was
      named the ESTI-Score. CONCLUSION: The ESTI-Score is a novel instrument designed
      to quantify the impact of ESTI on quality of life. Future study is required to
      determine its validity and responsiveness before use as an outcome measure in
      clinical trials.

PMID- 17034642
TI  - Identification of biomolecule mass transport and binding rate parameters in
      living cells by inverse modeling.
AB  - BACKGROUND: Quantification of in-vivo biomolecule mass transport and reaction
      rate parameters from experimental data obtained by Fluorescence Recovery after
      Photobleaching (FRAP) is becoming more important. METHODS AND RESULTS: The
      Osborne-More extended version of the Levenberg-Marquardt optimization algorithm
      was coupled with the experimental data obtained by the Fluorescence Recovery
      after Photobleaching (FRAP) protocol, and the numerical solution of a set of two
      partial differential equations governing macromolecule mass transport and
      reaction in living cells, to inversely estimate optimized values of the molecular
      diffusion coefficient and binding rate parameters of GFP-tagged glucocorticoid
      receptor. The results indicate that the FRAP protocol provides enough information
      to estimate one parameter uniquely using a nonlinear optimization technique.
      Coupling FRAP experimental data with the inverse modeling strategy, one can also
      uniquely estimate the individual values of the binding rate coefficients if the
      molecular diffusion coefficient is known. One can also simultaneously estimate
      the dissociation rate parameter and molecular diffusion coefficient given the
      pseudo-association rate parameter is known. However, the protocol provides
      insufficient information for unique simultaneous estimation of three parameters
      (diffusion coefficient and binding rate parameters) owing to the high
      intercorrelation between the molecular diffusion coefficient and pseudo
      association rate parameter. Attempts to estimate macromolecule mass transport and
      binding rate parameters simultaneously from FRAP data result in misleading
      conclusions regarding concentrations of free macromolecule and bound complex
      inside the cell, average binding time per vacant site, average time for diffusion
      of macromolecules from one site to the next, and slow or rapid mobility of
      biomolecules in cells. CONCLUSION: To obtain unique values for molecular
      diffusion coefficient and binding rate parameters from FRAP data, we propose
      conducting two FRAP experiments on the same class of macromolecule and cell. One
      experiment should be used to measure the molecular diffusion coefficient
      independently of binding in an effective diffusion regime and the other should be
      conducted in a reaction dominant or reaction-diffusion regime to quantify binding
      rate parameters. The method described in this paper is likely to be widely used
      to estimate in-vivo biomolecule mass transport and binding rate parameters.

PMID- 17034643
TI  - Signal stability of Cy3 and Cy5 on antibody microarrays.
AB  - BACKGROUND: The antibody microarray technique is a newly emerging proteomics tool
      for differential protein expression analyses that uses fluorescent dyes Cy 3 and
      Cy 5. Environmental factors, such as light exposure, can affect the signal
      intensity of fluorescent dyes on microarray slides thus, it is logical to scan
      microarray slides immediately after the final wash and drying processes. However,
      no research data are available concerning time-dependent changes of fluorescent
      signals on antibody microarray slides to this date. In the present study,
      microarray slides were preserved at -20 degrees C after regular microarray
      experiments and were rescanned at day 10, 20 and 30 to evaluate change in signal
      intensity. RESULTS: Fluorescent intensities of microarray spots were detected
      using a confocal laser scanner after the experiment at day 0, and re-examined at
      day 10, 20 and 30, respectively. Fluorescent intensities of rescanned microarray
      spots did not show significant changes when compared with those scanned
      immediately after standard microarray experiments. CONCLUSION: Microarray slides
      can be preserved and rescanned multiple times using a confocal laser scanner over
      a period of days or weeks.

PMID- 17034644
TI  - In vitro activity effects of combinations of cephalothin, dicloxacillin,
      imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus
      spp. strains.
AB  - BACKGROUND: combinations of drugs has been proposed as an alternative for
      oxacillin-resistant staphylococci infections, however, limited information about
      in vitro combinations are available for multi-resistant strains. The objective of
      this study was to describe the interaction of beta-lactams in combination with
      vancomycin or amikacin against 26 oxacillin and amikacin-resistant nosocomial
      Staphylococcus spp. isolates. METHODS: activity of dicloxacillin plus amikacin,
      cephalothin plus amikacin, cephalothin plus vancomycin, imipenem plus vancomycin
      and vancomycin plus amikacin was evaluated by checkerboard synergy tests and the
      fractional inhibitory concentration index (FIC) was calculated. RESULTS:
      dicloxacillin plus amikacin, and cephalothin plus amikacin were synergistic or
      partially synergistic in 84.6% and 100% respectively. For nearly half of the
      isolates the mean concentrations of dicloxacillin, cephalothin and amikacin at
      which FIC indexes were calculated were achievable therapeutically. Vancomycin
      plus amikacin had synergistic effect only against two isolates, and partially
      synergistic in 38.6%. For the combinations vancomycin plus cephalothin and
      vancomycin plus imipenem the effect was additive in 76.9% and 80.7% respectively.
      CONCLUSION: in this study the checkerboard analysis showed that amikacin in
      combination with cephalothin or dicloxacillin was synergistic against most of the
      resistant strains of S. aureus and coagulase-negative Staphylococcus. Vancomycin
      in combination with a beta-lactam (cephalothin or imipenem) showed additivity. An
      indifferent effect predominated for the combination vancomycin plus amikacin.
      Even though a synergistic effect is expected when using a beta-lactam plus
      amikacin combination, it is possible that the effect cannot be clinically
      achievable. Careful selection of antimicrobial combinations and initial MICs are
      mandatory for future evaluations.

PMID- 17034645
TI  - Factors associated with breastfeeding at six months postpartum in a group of
      Australian women.
AB  - BACKGROUND: Despite high levels of breastfeeding initiation in Australia, only 47
      percent of women are breastfeeding (exclusively or partially) six months later,
      with marked differences between social groups. It is important to identify women
      who are at increased risk of early cessation of breastfeeding. METHODS: Data from
      the three arms of a randomised controlled trial were pooled and analysed as a
      cohort using logistic regression to identify which factors predicted women
      continuing to feed any breast milk at six months postpartum. The original trial
      included 981 primiparous women attending a public, tertiary, women's hospital in
      Melbourne, Australia in 1999-2001. The trial evaluated the effect of two mid
      pregnancy educational interventions on breastfeeding initiation and duration. In
      the 889 women with six month outcomes available, neither intervention increased
      breastfeeding initiation nor duration compared to standard care. Independent
      variables were included in the predictive model based on the literature and
      discussion with peers and were each tested individually against the dependent
      variable (any breastfeeding at six months). RESULTS: Thirty-three independent
      variables of interest were identified, of which 25 qualified for inclusion in the
      preliminary regression model; 764 observations had complete data available.
      Factors remaining in the final model that were positively associated with
      breastfeeding any breast milk at six months were: a very strong desire to
      breastfeed; having been breastfed oneself as a baby; being born in an Asian
      country; and older maternal age. There was an increasing association with
      increasing age. Factors negatively associated with feeding any breast milk at six
      months were: a woman having no intention to breastfeed six months or more;
      smoking 20 or more cigarettes per day pre-pregnancy; not attending childbirth
      education; maternal obesity; having self-reported depression in the six months
      after birth; and the baby receiving infant formula while in hospital. CONCLUSION:
      In addition to the factors commonly reported as being associated with
      breastfeeding in previous work, this study found a negative association between
      breastfeeding outcomes and giving babies infant formula in hospital, a high
      maternal body mass index, and self-reported maternal depression or anxiety in the
      six months after the baby was born. Interventions that seek to increase
      breastfeeding should consider focusing on women who wish to breastfeed but are at
      high risk of early discontinuation.

PMID- 17034646
TI  - Alveolar proteinosis in a patient recovering from Pneumocystis carinii infection:
      a case report with a review of literature.
AB  - BACKGROUND: Pulmonary alveolar proteinosis is a rare lung disorder, which was
      first reported as idiopathic condition in 1958. The prevalence of acquired
      pulmonary alveolar proteinosis has been estimated to be 0.37 per 100,000
      population. The cause of this condition is not entirely clear. We present
      alveolar proteinosis in a case recently treated for pulmonary Pneumocystis
      carinii infection. CASE PRESENTATION: A 25-year-old Caucasian female presented
      with shortness of breath during management of acute pancreatitis. She had a heart
      transplant six years ago, a distal pancreatectomy secondary to pancreatitis two
      years ago, chronic renal failure secondary to Prograft taken for six years to
      suppress transplant rejection, and a more recent history of Pneumocystis carinii
      infection treated in the preceding 21 days with augmented doses of Bactrim
      (Trimethoprim, Sulfamethoxazole). She had bilateral pleural effusions with
      radiological and clinical features suspicious for interstitial lung disease.
      Cytopathologic evaluation of broncho-alveolar lavage (BAL) showed hyaline
      alveolar casts admixed with amorphous debris and scant chronic inflammatory
      cells, consistent with alveolar proteinosis. GMS and PAS stains were negative for
      P. carinii. Direct Fluorescent Antibody (DFA) test for P. carinii performed on
      the BAL specimen in our Microbiology Lab had been repeatedly negative.
      CONCLUSION: Cytopathological findings in bronchoalveolar lavage, with clinical
      differential diagnosis of interstitial lung disease, were diagnostic. Pulmonary
      alveolar proteinosis after recent treatment for P. carinii infection suggests a
      relationship of pulmonary alveolar proteinosis with P. carinii infection in the
      immunocompromised patient.

PMID- 17034647
TI  - 5' long terminal repeat (LTR)-selective methylation of latently infected HIV-1
      provirus that is demethylated by reactivation signals.
AB  - We previously described selective hypermethylation of the 5'-long terminal repeat
      (LTR) of HTLV-1 provirus in vivo and in vitro. This prompted us to analyze CpG
      methylation of the two LTRs of the HIV provirus in chronically infected cell
      lines. The results demonstrate selective hypermethylation of the 5' LTR of the
      HIV provirus in ACH-2 cells. Moreover, induction of viral gene expression by TNF
      alpha resulted in demethylation of the 5'-LTR. These results suggest that
      selective epigenetic modification of the 5'LTR of the HIV-1 provirus may be an
      important mechanism by which proviral activity is suppressed.

PMID- 17034648
TI  - Crimean-Congo haemorrhagic fever in Kosova : a fatal case report.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection
      described in about 30 countries around the world. The authors report a fatal case
      of Crimean-Congo hemorrhagic fever (CCHF) observed in a patient from Kosova. The
      diagnosis of CCHF was confirmed by reverse transcription-PCR. Late diagnosis
      decreased the efficacy of treatment and patient died due to severe complications
      of infection.

PMID- 17034649
TI  - Creating a medical English-Swedish dictionary using interactive word alignment.
AB  - BACKGROUND: This paper reports on a parallel collection of rubrics from the
      medical terminology systems ICD-10, ICF, MeSH, NCSP and KSH97-P and its use for
      semi-automatic creation of an English-Swedish dictionary of medical terminology.
      The methods presented are relevant for many other West European language pairs
      than English-Swedish. METHODS: The medical terminology systems were collected in
      electronic format in both English and Swedish and the rubrics were extracted in
      parallel language pairs. Initially, interactive word alignment was used to create
      training data from a sample. Then the training data were utilised in automatic
      word alignment in order to generate candidate term pairs. The last step was
      manual verification of the term pair candidates. RESULTS: A dictionary of 31,000
      verified entries has been created in less than three man weeks, thus with
      considerably less time and effort needed compared to a manual approach, and
      without compromising quality. As a side effect of our work we found 40 different
      translation problems in the terminology systems and these results indicate the
      power of the method for finding inconsistencies in terminology translations. We
      also report on some factors that may contribute to making the process of
      dictionary creation with similar tools even more expedient. Finally, the
      contribution is discussed in relation to other ongoing efforts in constructing
      medical lexicons for non-English languages. CONCLUSION: In three man weeks we
      were able to produce a medical English-Swedish dictionary consisting of 31,000
      entries and also found hidden translation errors in the utilized medical
      terminology systems.

PMID- 17034650
TI  - Studies on cell-cycle synchronization in the asexual erythrocytic stages of
      Plasmodium falciparum.
AB  - Multiplication of Plasmodium parasites within human erythrocytes is essential to
      malarial disease. The cell-division cycle of this organism, however, is still
      poorly understood. In other eukaryotes, various techniques for (apparent) cell
      cycle synchronization have been used to shed light on the mechanisms involved in
      cell division and its control. Thus far there is no technique for cell-cycle
      synchronization (as opposed to selection of parasites of a limited age-range) in
      Plasmodium. We therefore investigated the possibility that inhibitors of DNA
      synthesis, the mitotic spindle, or cell-cycle control elements (such as cyclin
      dependent kinases) could be used to synchronize P. falciparum cultures to a
      particular cell-cycle phase. Surprisingly, most of these compounds did not cause
      a block at a specific phase. Three compounds, Hoechst 33342, roscovitine and L
      mimosine, did block development at the trophozoite-schizont transition (S or G2
      phase). The block caused by the latter 2 inhibitors was reversible, suggesting
      that they might be used as synchronizing agents. However, a consideration of the
      perturbing effects of inhibitors and problems with 'batch' synchronization
      techniques in general lead us to believe that any results obtained using
      roscovitine- or L-mimosine-treated parasites may not be reflective of the normal
      cell cycle.

PMID- 17034651
TI  - Assessment and prevention of gastrointestinal toxicity of non-steroidal anti
      inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic,
      anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The
      serious gastrointestinal side-effects associated with these drugs are of concern
      and pose a significant obstacle to their use. This review discusses the
      pathogenic mechanisms by which the conventional acidic NSAIDs induce
      gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects.
      Methods of assessment of NSAID-induced enteropathy are reviewed, with particular
      emphasis on the use of functional measurement of NSAID-induced changes in the
      gastrointestinal tract. The advances in our knowledge of the pathogenesis of
      these effects have resulted in the development of a range of novel NSAIDs. Where
      functional assessment of the effects of NSAIDs has been employed, it appears to
      be more useful as an indicator of early-stage changes rather than a predictor of
      the effects of long-term NSAID exposure. Successful pharmaceutical strategies now
      offer considerable promise for reducing the severity of NSAID damage to the
      gastrointestinal tract. The utility of intestinal permeability measurements for
      selection and assessment of these strategies is discussed.

PMID- 17034652
TI  - Factorial designed experiment to study the effects of excipients on the
      mechanical properties of pellets.
AB  - The aim of this work was to determine the effects of formulation factors on the
      mechanical properties of pellets produced by the process of extrusion and
      spheronisation. A range of properties from a simple fracture load to detailed
      load/displacement curves were used to study the effects of the levels of lactose
      monohydrate and glyceryl monostearate on the mechanical properties of pellets in
      terms of their surface tensile strength, pellet deformability and linear strain.
      A series of independent 2(2)-factorial designs were employed to establish the
      relationships between composition of the formulations and pellet properties,
      whereby the concept of an excess variable was explored. It was found that the
      spheronisation aid used, microcrystalline cellulose, is the domineering factor in
      most mechanical properties studied, except for the surface tensile strength,
      which decreased significantly with an increase in glyceryl monostearate
      concentration. The change in binder liquid from water to a water/ethanol mixture
      further changed the behaviour of the systems significantly. The assumption of an
      excess variable being less critical for the statistical outcome of a factorial
      experiment has not been found feasible for the systems studied.

PMID- 17034653
TI  - Intranasal midazolam: a comparison of two delivery devices in human volunteers.
AB  - Bidirectional nasal drug delivery is a new administration principle with improved
      deposition pattern that may increase nasal drug uptake. Twelve healthy subjects
      were included in this open, non-randomized 3-way crossover study: midazolam (3.4
      mg) intravenously (1 mg mL (-1)), or nasally by bidirectional or traditional
      spray (2 x100 microL of a 17 mg mL(-1) nasal midazolam formulation). The primary
      outcome was bioavailability. Blood samples were drawn for 6 h for determination
      (gas-chromatography-mass-spectrometry) of midazolam and 1-OH-midazolam.
      Pharmacokinetic calculations were based on non-compartmental modelling, sedation
      assessed by a subjective 0-10 NRS-scale, and nasal dimensions by non-invasive
      acoustic rhinometry. Mean bioavailabilities were 0.68-0.71, and Tmax 15 min for
      the sprays, which also were bioequivalent (ratio geometric means (90%) CI: 97.6%
      (90% CI 83.5; 113.9)). Sedation after bidirectional spray followed intravenous
      sedation closely, while sedation after the traditional spray was less pronounced.
      A negative correlation between Cmax and smallest cross-sectional area was seen.
      Adverse effects such as local irritation did not differ significantly between the
      sprays. Apparently bidirectional delivery did not increase systemic
      bioavailability of midazolam. We cannot disregard that only the traditional spray
      caused less sedation than intravenous administration. This finding needs to be
      confirmed in trials designed for this purpose.

PMID- 17034654
TI  - Fast-dissolving microparticles fail to show improved oral bioavailability.
AB  - Oral dosage forms are the preferred means of delivering drugs for systemic
      absorption. However, development problems occur for drugs with poor water
      solubility and/or gastrointestinal permeability. It is generally believed that
      the in-vivo bioavailability of poorly water-soluble drugs from Class II of the
      Biopharmaceutics Classification System can be improved by increasing the
      dissolution rate. We have attempted to increase the in-vivo oral bioavailability
      of a model Class II drug (griseofulvin) by preparing rapidly-dissolving
      particles. The solvent-diffusion method was used to prepare particles with
      hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies
      were conducted in rats. The griseofulvin particles produced were bipyramidal in
      habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline
      drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The
      latter and the small particle size ensured rapid particle dispersion and
      dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the
      bipyramidal particles had released approximately 70% of drug compared with
      approximately 10% from the starting material (particle size 12.61 +/- 1.11
      microm). However, the rapid and increased drug dissolution in-vitro was not
      translated to rapid and enhanced absorption in-vivo, and the oral bioavailability
      of the model drug was found to be the same from the control and from the
      bipyramidal particles. The poor in-vivo performance of the bipyramidal particles
      showed that although the dissolution rate of a Class II drug is thought to be a
      good indicator of its in-vivo bioavailability, this is not always the case.

PMID- 17034655
TI  - Histological evaluation of buccal penetration enhancement properties of chitosan
      and trimethyl chitosan.
AB  - The aim of the present work was to compare the penetration enhancement properties
      of chitosan hydrochloride (HCS) both as a polymeric solution and as a
      nanoparticulate system with that of trimethyl chitosan hydrochloride (TMC) on
      buccal mucosa. The hydrophilic high molecular weight fluorescein isothiocyanate
      dextran (FD4; 4400 Da) was used as a macromolecule model. The mechanism involved
      in the HCS (solution and nanoparticles) and TMC solution penetration enhancement
      was investigated on pig buccal mucosa, characterized by having stratified
      epithelium and lacking in tight junctions. The permeation/penetration of FD4 and
      the change in morphology and histology of the mucosa after contact with the
      polymers were assessed: the experiments were performed ex-vivo by applying the
      formulations on excised porcine buccal tissue. For the morphology and the
      histology studies, the epithelial cell layers from freshly excised pig buccal
      mucosa were analysed with light microscopy by means of routine histopathology
      analysis (haematoxylin and eosin staining and Toluidine blue staining) and
      immunohistochemistry reactions. The organization of desmosomal junctions was
      assessed by means of an immunochemical reaction on desmosomes and transmission
      electron microscopy. Confocal laser scanning microscopy (CLSM) was used to find
      evidence of the location of FD4 in the tissue. Furthermore, the increase of the
      FD4 apparent permeability coefficient was quantified by means of Franz diffusion
      cells using isolated buccal epithelium to demonstrate the penetration enhancement
      properties of the polymer systems. Morphological analysis, performed by light
      microscopy, transmission electron microscopy and CLSM, suggests a similar
      mechanism of penetration enhancement for both HCS and TMC solutions and for HCS
      nanoparticles. Such a mechanism probably involves a repackaging of the epithelial
      cells up to the basal membrane and a partial disarrangement of desmosomes. The
      cell viability and the nuclear integrity indicated on the semi-thin section
      stained with Toluidine blue and by CLSM analysis, respectively, suggest that HCS
      as a polymer solution and a nanoparticulate system, and TMC polymer solution, do
      not cause cell damage. Trimethyl chitosan and chitosan nanoparticulate systems
      were able to increase FD4 permeation across buccal epithelium to a greater extent
      than the chitosan solution.

PMID- 17034656
TI  - Receptor dependent cellular uptake of synthetic low density lipoprotein by
      mammalian cells in serum-free tissue culture.
AB  - Low density lipoprotein (LDL) is a normal plasma component, which is of interest
      in a number of research areas such as hypercholesterolaemia, drug targeting in
      cancer chemotherapy and as a lipid supplement in tissue culture systems.
      Currently, however, it can only be obtained by extraction from fresh plasma
      samples, which yields only small quantities. Synthetic LDL (sLDL) has been
      prepared using readily available lipid components coupled with a synthetic
      amphiphatic peptide molecule containing the apoprotein B receptor sequence. sLDL
      was capable of supporting the growth of Chinese Hamster Ovary (CHO) and
      fibroblast cells in serum-free culture media in a cholesterol-dependent manner
      that was related to the presence of the receptor peptide molecule. sLDL could be
      fluorescently labelled with 3,3'-dioctadecyloxalocarbocyanine perchlorate (DiO),
      and once labelled was assimilated by CHO and fibroblast cells in a time- and
      temperature-dependent manner that was dependent upon the presence of the receptor
      peptide. In addition, assimilation was reduced by an excess of unlabelled native
      LDL. The results indicated that the interaction of sLDL with CHO and fibroblast
      cells occurred via a receptor dependent system, most likely the LDL cellular
      receptor. sLDL is therefore a useful, easily obtained substitute for native LDL
      with potential applications in the areas of drug targeting to cells and serum
      free tissue culture systems.

PMID- 17034657
TI  - Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives
      related to alpha-asarone.
AB  - The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic
      acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2
      methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2
      propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2
      propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate
      (6)] related to alpha-asarone have been reported previously as hypolipidaemic
      agents in diet-induced hyperlipidaemic mice. We have aimed to expand the
      pharmacological profile of these derivatives by investigating their
      hypolipidaemic activity in rats and mice under different experimental conditions.
      The antiplatelet activity was tested also in-vitro from blood derived from
      consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at
      oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and
      LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to
      hypercholesterolaemic rats at the same doses for seven days also produced a
      reduction in the content of these same lipoproteins. In neither case were the
      high-density lipoprotein cholesterol and triglyceride concentrations affected.
      However, practically all tested compounds were found to be hypocholesterolaemic
      agents, and were shown to effectively lower low-density lipoprotein cholesterol
      and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of
      50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout
      the experimental period in their therapeutic ranges. Triton-induced
      hypercholesterolaemic mice appeared to be a desirable model for this class of
      hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly
      inhibited ADP-induced aggregation in-vitro. These findings indicated that all of
      these compounds appeared to be promising for the treatment of human
      hyperlipidaemia and thrombotic diseases.

PMID- 17034658
TI  - Decreased B16F10 melanoma growth and impaired tumour vascularization in BDF1 mice
      with quercetin-cyclodextrin binary system.
AB  - The aim of this work was to study the inclusion behaviour of a poorly water
      soluble bioflavonoid, quercetin, towards sulfobutyl ether-7beta-cyclodextrin. It
      also involves angiogenesis inhibition in-vivo in addition to in-vitro human
      cancer cell growth inhibition study of quercetin and its cyclodextrin complex.
      Drug-cyclodextrin solid inclusion complexes were prepared and characterized in
      solution and in the solid state. An in-vitro anti-proliferation study using plain
      drug and its solubilized form was carried out on human cancer cell lines of
      different origin. Further, an in-vivo tumour growth inhibition study was carried
      out using a mouse melanoma model. Histological sections of tumours were examined
      for the evaluation of tumour microvessel density. Significant enhancement of the
      solubility and dissolution rate of the quercetin, which occurred after
      complexation, might be attributed to the decrease in crystallinity of drug.
      SBE7betaCD complex of quercetin was more potent for inhibiting cell proliferation
      in human erythroleukaemia and cervix cancer cells. Decreased tumour microvessel
      density in mouse melanoma after oral quercetin administration led to diminished
      tumour cell proliferation. Quercetin-SBE7betaCD complex showed significantly
      improved anti-cancer activity at much lower concentration than the plain drug,
      providing evidence for dose reduction without affecting therapeutic efficacy when
      using cyclodextrin carriers.

PMID- 17034659
TI  - Metabolism of troglitazone in hepatocytes isolated from experimentally induced
      diabetic rats.
AB  - Troglitazone (TGZ), the prototype 2,4-thiazolidinedione antidiabetic agent, is
      associated with hepatotoxicity in patients with Type 2 diabetes. Although the
      mechanism of toxicity has not been established, alterations in the clearance of
      TGZ from in-vitro hepatocyte cultures through metabolic conjugation reactions are
      believed to modulate the toxicity of the compound. In this study, the metabolism
      of TGZ in freshly isolated hepatocytes from the fat-fed streptozotocin-treated
      rat model of Type 2 diabetes is described. Biochemical parameters such as
      cellular reduced glutathione content, content of cytochromes P450 and b5, and the
      expression of glutathione-S-transferase alpha (subunits Ya and Yc2) were not
      affected by the induced diabetes. TGZ was metabolized primarily to a sulfonate, a
      quinone and a glucuronide in both control and experimentally diabetic animals.
      However, metabolism after induction of diabetes was characterized by a moderate
      increase in sulfation, a decrease in the elimination half-life of TGZ and the
      absence of the minor metabolites of TGZ, notably the glutathione adduct of the
      putative reactive intermediate (m/z = 747 (M + H)+; m/z = 745 (M - H)-).

PMID- 17034660
TI  - Effect of the administration of tiagabine and gabapentin on rabbit
      electroencephalogram activity.
AB  - New generation antiepileptic drugs, including gabapentin and tiagabine, are used
      in monotherapy or in combination with other drugs for specific seizure types. The
      multidirectional mechanism of activity and varied pharmacological properties of
      these drugs suggest that they could also be used in the therapy of other
      diseases. A possible limitation of new generation antiepileptic drugs is the
      incidence of CNS-related adverse effects. Few studies have assessed the effect of
      new antiepileptic drugs on electroencephalogram (EEG) recordings in subjects
      using these drugs for diseases other than epilepsy. The aim of this study was to
      determine the effects of tiagabine and gabapentin on EEG recordings from the
      midbrain reticular formation, dorsal hippocampus and frontal cortex in rabbits.
      Tiagabine was administered orally at a single dose of 5 and 20 mg kg(-1), or
      repeatedly at a dose of 5 mg kg(-1) (twice a day) for 14 days. Gabapentin was
      administered orally at a single dose of 25 and 100 mg kg(-1), or repeatedly at a
      dose of 25 mg kg(-1) (twice a day) for 14 days. Both tiagabine and gabapentin
      caused changes indicative of CNS inhibitory properties, which may be associated
      with the adverse effects of the drugs. After repeated doses of the drugs, the
      changes in EEG recordings were less pronounced than after single doses, which may
      indicate adaptive changes. The hippocampus was found to be the least sensitive to
      the effect of gabapentin.

PMID- 17034662
TI  - Relaxant effect of Crocus sativus (saffron) on guinea-pig tracheal chains and its
      possible mechanisms.
AB  - As indicated in ancient Iranian medical books, Crocus sativus has therapeutic
      effects on respiratory diseases. The relaxant effect of this plant has been
      observed also on smooth muscles in previous studies. Therefore, in this study the
      relaxant effects of aqueous-ethanolic extracts of C. sativus and one of its main
      constituents, safranal, were examined on guinea-pig tracheal chains. The relaxant
      effects of four cumulative concentrations of aqueous-ethanolic extract (0.15,
      0.3, 0.45, and 0.60 g %) and safranal (0.15, 0.30, 0.45, and 0.60 mL 0.2 mg mL(
      1) solution) in comparison with saline, as negative control, and four cumulative
      concentrations of theophylline (0.15, 0.30, 0.45, and 0.60 mM), as positive
      control, were examined using guinea-pig precontracted tracheal chains. The
      tracheal chains had been precontracted by three different methods. Group 1 had
      been precontracted using 10 microM methacholine. The other two groups had been
      precontracted using 60 mM KCl at two different conditions: non-incubated tissues
      (group 2) and tissues incubated with 1 microM propranolol, 1 microM
      chlorpheniramine and 1 microM atropine (group 3) (for each group, n = 6). In
      group 1 all concentrations of theophylline, extract and safranal showed
      significant relaxant effects compared with saline (P < 0.05 to P < 0.001). In
      group 2 theophylline, extract and safranal showed concentration-dependent
      relaxant effects also compared with saline (P < 0.05 to P < 0.001 for different
      concentrations except two low concentrations of safranal). However, in group 3
      the extracts of C. sativus showed a weak relaxant effect (P < 0.05 only for the
      highest concentration). The effects of the last concentration of safranal (0.60
      mL 0.2 mg mL(-1) solution) in group 1, and all its concentrations in group 2 were
      significantly lower than those of theophylline (P < 0.05 to P < 0.001). In
      addition, the effects of safranal 0.45 and 0.60 mL 0.2 mg mL(-1) solution in
      groups 1 and 2 were significantly lower than that of C. sativus extract. There
      were significant correlations between the relaxant effects and concentrations for
      extract, safranal and theophylline in all experimental groups (P < 0.001 for all
      cases). These results showed a potent relaxant effect of C. sativus on tracheal
      chains of guinea-pigs that was comparable to or even higher than that of
      theophylline at the concentrations used. The results indicated that safranal was,
      at least in part, responsible for the relaxant effect of C. sativus.

PMID- 17034661
TI  - Protective effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes
      and glycoproteins in streptozotocin-induced diabetic rats.
AB  - The protective role of rutin on lipids, lipoproteins, lipid metabolizing enzymes
      and glycoproteins in streptozotocin-induced diabetic rats has been studied. A
      single intraperitoneal injection of streptozotocin (50 mg kg(-1)) to rats led to
      a significant (P < 0.05) increase in the levels of lipids (cholesterol,
      triglycerides, free fatty acids and phospholipids) in plasma and tissues (liver,
      kidney, heart and brain). The levels of low density and very low density
      lipoprotein (LDL and VLDL, respectively) cholesterol were increased, whereas the
      levels of high density lipoprotein (HDL) cholesterol were decreased significantly
      (P < 0.05) in plasma. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG
      CoA) reductase increased significantly (P < 0.05) in liver, kidney and heart, and
      the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase
      (LCAT) decreased significantly (P < 0.05) in the plasma of diabetic rats.
      Streptozotocin injection also increased the levels of glycoproteins such as
      hexose, hexosamine, fucose and sialic acid in plasma, liver and kidney. Oral
      administration of rutin to streptozotocin-induced diabetic rats significantly (P
      < 0.05) decreased the levels of lipids in plasma and tissues. The levels of
      plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterol
      decreased significantly (P < 0.05). The activity of HMG CoA reductase decreased
      in the tissues and the activity of plasma LPL and LCAT increased significantly (P
      < 0.05). The levels of glycoproteins were found to be significantly (P < 0.05)
      decreased in plasma, liver and kidney of rutin-treated diabetic rats. Rutin
      administration to normal rats did not exhibit any significant (P < 0.05) changes
      in any of the parameters studied. In conclusion, the beneficial effect of rutin
      on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins could be
      due to its antioxidant property.

PMID- 17034663
TI  - Protective effects of the Alisma orientalis extract on the experimental
      nonalcoholic fatty liver disease.
AB  - The aim of this investigation was to evaluate the efficacy of Alisma orientalis
      methanolic extract (AOME) on the experimental nonalcoholic fatty liver disease
      (NAFLD) induced by high-fat diet. Rats were fed with high-fat diet for six weeks
      and then gavaged the AOME for another six weeks. Typical pathological symptoms of
      NAFLD occurred in the high-fat diet rats. Administration with the AOME (150,300
      and 600 mg kg (-1)) markedly decreased the serum and liver lipids; the high level
      of fasting serum glucose was reduced and insulin resistance was improved. The
      AOME treatment was also helpful in preventing the oxidative stress by lessening
      lipid peroxidation and activating antioxidant enzymes. Markers of the liver
      injury, aminotransferase abnormalities and hepatomegaly were improved and
      morphological changes, such as liver steatosis, mixed inflammation and collagen
      deposition, were lessened in rats treated with the AOME. These results suggested
      that the AOME showed hepatoprotective effects on NAFLD and may be a potential
      clinical application for treatment of this chronic liver disease.

PMID- 17034664
TI  - Novel selective cytotoxicity of wild sarsaparilla rhizome extract.
AB  - Among six fractions, including total extract and fractions of hexane, ethyl
      acetate, butanol, water and boiling water extracted and separated from wild
      sarsaparilla rhizome, the hexane fraction (HRW) was the most effective in
      eliminating four different human cancer cell lines with cellular viability less
      than 6.8%. HRW exhibited the highest potency against human leukaemia cells with
      an IC50 (concentration that inhibited the growth rate of cells by 50%) of 3.3 +/-
      0.3 microg mL(-1), which was 17.6-fold smaller than that against normal human
      umbilical vein endothelial cells (IC50, 58.0 +/- 1.5 microg mL(-1)). For its rich
      natural resources, simple extraction procedure and high yield (3.2%), HRW has the
      potential to be developed as a selective anti-cancer nutraceutical or
      pharmaceutical natural health product with low side effects and high economical
      return.

PMID- 17034665
TI  - The inhibition of paw oedema formation caused by the oil of Copaifera multijuga
      Hayne and its fractions.
AB  - Two oils exuded from a Copaifera multijuga Hayne tree (Leguminosae
      Caesalpinoideae), collected from the same plant, but in different periods of the
      year, and the hexanic, dichloromethanic and methanolic fractions of one of these
      oils were analysed by high-resolution gas chromatography (HRGC) and HRGC coupled
      with mass spectrometry (HRGC-MS). In addition, the in-vivo preliminary anti
      oedematogenic actions of the oil and some fractions of it were assessed against
      carrageenan- and bradykinin-induced oedema formation in the rat paw. Twenty-seven
      sesquiterpenes and six diterpenes were identified, beta-caryophyllene, alpha
      copaene and copalic acid being the main components. The dichloromethanic and
      methanolic fractions obtained from C. multijuga oil given by the intraperitoneal
      route caused a significant inhibition of paw oedema caused by carrageenan with
      inhibition of 49 +/- 13% and 64 +/- 9 %, respectively. Likewise, dexamethasone
      (the positive control drug) also greatly inhibited carrageenan-induced paw oedema
      formation (60 +/- 4% at 2 h). The hexanic fraction also significantly inhibited
      (50 +/- 6%) the paw oedema formation caused by bradykinin. These results suggest
      the presence of still non-identified active terpene compounds in the oil of C.
      multijuga that exhibit anti-oedematogenic properties. Of note, the yield of these
      compounds and the pharmacological actions of the oil, exhibited great seasonal
      variations, a relevant aspect that should be carefully observed for the correct
      medicinal use of this plant by the population.

PMID- 17034666
TI  - Protective effect of Mediterranean fish oil extracts on heat-induced denaturation
      of albumin.
AB  - Three oily extracts, obtained by acetone extraction from the entrails of
      different varieties of Mediterranean fishes, such as mackerel (Scomber scombrus),
      sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus), were
      characterized to determine their unsaturated fatty acid content. In an in-vitro
      model, their inhibitory effect was then evaluated against protein aggregation and
      their protective efficacy against heat-induced albumin denaturation assessed. The
      fish oil extracts tested in this study presented a significant amount of
      unsaturated fatty acids; in particular the extract obtained from the entrails of
      horse mackerel proved to have higher concentrations of DHA (docosahexaenoic acid)
      and oleic acid compared with the other two oils. The in-vitro study revealed an
      interesting protective effect of the oil extracts (particularly the horse
      mackerel extract) against heat-induced denaturation of albumin.

PMID- 17034667
TI  - N, N' (4,5-dihydro-1h-imidazol-2-yl)3-aza-1,10-decane-diamine and N, N'(4,5
      dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell
      proliferation as selective ligands towards topoisomerase II.
AB  - New alkyl imidazoline derivatives have been synthesized as potential anti-cancer
      agents. The anti-proliferative activity of these compounds, evaluated against
      representative human haematological and solid neoplastic cell lines, showed that
      N, N'-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decane-diamine (8) and N, N'-di
      (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most
      active compounds; in fact, they inhibited the cell proliferation at submicromolar
      concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of
      topoisomerase II at concentrations comparable with those of the reference
      topoisomerase II inhibitor, etoposide.

PMID- 17034669
TI  - Difficult pain syndromes: bone pain, visceral pain, and neuropathic pain.
AB  - Cancer pain is prevalent in approximately two thirds of all cancer patients and
      can undermine the quality of life in this patient population. Uncontrolled pain
      can cause physical as well as psychological distress in cancer patients. As the
      disease progresses in cancer, pain and suffering increase. Knowledge about pain
      management is paramount in the comprehensive treatment of cancer patients.
      Difficult cancer pain syndromes may arise from interruption of bone, viscera, and
      neural structures by malignant spread of the disease. Familiarity with opioids,
      adjuvants, and procedures that can abate pain in cancer patients is discussed in
      a practical manner for clinical application in this text.

PMID- 17034670
TI  - New approaches to chemotherapy-induced nausea and vomiting: from
      neuropharmacology to clinical investigations.
AB  - Nausea and vomiting are considered to be among the most distressing consequences
      of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor
      antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV),
      including ondansetron, granisetron, and dolasetron. These agents provide
      significant improvement in the management of acute emesis but are ineffective at
      preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist,
      palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was
      found to be effective in preventing delayed CINV. Indeed, palonosetron was the
      first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention
      of both acute and delayed CINV. More recently, studies on the role of substance P
      in the emetic process led to the development of aprepitant (Emend) for the
      prevention of delayed emesis in combination with 5-HT(3) receptor antagonists.
      Despite these major advances, CINV remains uncontrolled in some patients. Current
      efforts are focused on treating refractory emesis and include both the clinical
      evaluation of compounds marketed for other indications and the preclinical
      evaluation of novel molecules targeting other transmitters in the emetic pathway.
      Ongoing work in pharmacogenomics has postulated several candidate genes that
      could be involved in emetic sensitivity and responsiveness to antiemetic therapy.
      Investigations into the pharmacogenomics of CINV may someday be able to aid in
      the identification of high risk patients and patients unlikely to respond to
      conventional therapies.

PMID- 17034671
TI  - Treatment of mucositis, including new medications.
AB  - Mucositis is a clinically important and sometimes dose-limiting complication of
      cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of
      life, lead to sepsis, and have significant economic impact. Recent modeling of
      the toxicity has been based on the continuum of clinical signs and symptoms of
      mucositis involving the alimentary tract, including both oral and
      gastrointestinal sites. The pathogenesis of oral and gastrointestinal mucositis
      is multifactorial and complex. In recent years, there has been a substantial
      increase in both basic and clinical research related to mucosal injury in cancer
      patients. Since most of this research has been directed to oral mucositis, the
      present review principally addresses this component of the toxicity. Morbidity,
      economic impact, pathogenesis and clinical course of mucositis are discussed. In
      addition, several agents in clinical development for mucositis are discussed in
      the context of the current pathobiologic model as well as the recently updated
      evidence-based clinical management guidelines.

PMID- 17034672
TI  - Constipation and diarrhea in patients with cancer.
AB  - Constipation and diarrhea are both common problems in patients with advanced
      cancer. They are source of major morbidity and distress. Constipation is,
      overall, more common that diarrhea. Diarrhea may be severe and, in some cases,
      associated with life-threatening dehydration and electrolyte abnormalities.
      Indeed, with some of the newer chemotherapy agents, this is a problem seen with
      increasing frequency. Oncologists must be familiar with the common causes of
      constipation and diarrhea in cancer patients and the strategies to evaluate and
      manage these common and distressing symptoms. Both with constipation and
      diarrhea, there is a differential diagnosis. In many cases, management can be
      complex and challenging. Approaches to diagnosis, evaluation, and management are
      reviewed.

PMID- 17034673
TI  - Dyspnea.
AB  - Dyspnea, defined as uncomfortable or labored breathing, is a common and often
      devastating cause of distress for patients and their caregivers with advanced
      cancer and other life-threatening illnesses. The mechanism by which dyspnea
      develops is not fully understood, but it involves integration of the central
      respiratory complex with the sensory (perceptual) cortex. The gold standard of
      diagnosis is patient self-report. Careful assessment should be undertaken to
      identify reversible existing causes. Systemic opioids are the first-line therapy
      for symptomatic management, along with other general comfort measures
      (positioning, cool air, calming environment). Medical or surgical management can
      be directed toward underlying causes. Advanced care planning should include
      discussions concerning the burdens and benefits of medical/surgical management of
      underlying causes of dyspnea to more effectively direct goals of care. This
      article reviews current literature on dyspnea, with a focus on items published
      since 2000.

PMID- 17034674
TI  - Cancer-related fatigue: the evidence base for assessment and management.
AB  - PURPOSE: Cancer-related fatigue contributes to negative outcomes relative to
      psychosocial and symptom distress, functional status, and quality of life, and
      yet it is often underdiagnosed and management is frequently suboptimal. DESIGN:
      Systematic database searches were conducted, and primary research reports and
      meta-analyses of quantitative studies of interventions for fatigue published in
      English were identified and critically examined. RESULTS: This paper reviews the
      etiology and evaluation of cancer-related fatigue and analyzes current empirical
      evidence supporting pharmacologic and nonpharmacologic techniques for its
      management. DISCUSSION: A variety of pharmacologic and nonpharmacologic
      techniques to manage cancer-related fatigue have been studied, although most of
      the evidence is from single-arm pilot studies with small sample sizes, rather
      than from adequately powered, multicenter, randomized controlled trials.
      Continued research in ethnically and racially diverse samples is needed to
      identify the interventions that are most effective in specific cancer
      subpopulations and to develop and test interventions for fatigue at each phase in
      the illness trajectory.

PMID- 17034675
TI  - Depression and anxiety.
AB  - Anxiety and depression are common in patients with cancer and in palliative care
      settings. These symptoms can be reactive to the illness or can be related to the
      direct physiologic effects of the disease or to drug therapies. Effective
      treatment of these symptoms includes both psychopharmacologic and
      psychotherapeutic approaches. The newer antidepressants, anxiolytics, and
      hypnotics are better tolerated and can be continued safely if necessary, or they
      can be reduced and discontinued as symptoms improve.

PMID- 17034676
TI  - Interdisciplinary spiritual care for seriously ill and dying patients: a
      collaborative model.
AB  - Spirituality is essential to healthcare. It is that part of human beings that
      seeks meaning and purpose in life. Spirituality in the clinical setting can be
      manifested as spiritual distress or as resources of strength. Patients' spiritual
      beliefs can impact diagnosis and treatment. Spiritual care involves an intrinsic
      aspect of care, which underlies compassionate and altruistic caregiving and is an
      important element of professionalism amongst the various healthcare
      professionals. It also involves an extrinsic element, which includes spiritual
      history, assessment of spiritual issues, as well as resources of strength and
      incorporation of patients' spiritual beliefs and practices into the treatment or
      care plan. Spiritual care is interdisciplinary care-each member of the
      interdisciplinary team has responsibilities to provide spiritual care. The
      chaplain is the trained spiritual care expert on the team. Optimally, all
      healthcare professionals, including the chaplain, on the team interact with each
      other to develop and implement the spiritual care plan for the patient in a fully
      collaborative model.

PMID- 17034677
TI  - Communication at times of transitions: how to help patients cope with loss and re
      define hope.
AB  - Patients undergo multiple transitions during the course of their cancer care.
      Oncologists are uniquely positioned to help patients through these transitions.
      When patients' situations change, they must cope with loss and associated
      negative emotions. They then are able to redefine hope. During transitions,
      patients want their oncologists to provide biomedical information, show that they
      care about and understand them as individuals, and balance hope and realism.
      Eliciting concerns and expressing empathy shows patients that their oncologist
      cares about and understands them and also helps patients to cope with the loss
      and negative emotions that transitions create. Oncologists can maintain hope by
      being sensitive to what patients are ready to hear when, and by helping them
      discover and identify realistic hopes. This is accomplished with the Ask-Tell-Ask
      and Hope for the Best, Prepare for the Worst techniques, and most importantly by
      being curious about patients' hopes and fears.

PMID- 17034678
TI  - Complementary medicine in palliative care and cancer symptom management.
AB  - Complementary and alternative medicine (CAM) use among cancer patients varies
      according to geographical area, gender, and disease diagnosis. The prevalence of
      CAM use among cancer patients in the United States has been estimated to be
      between 7% and 54%. Most cancer patients use CAM with the hope of boosting the
      immune system, relieving pain, and controlling side effects related to disease or
      treatment. Only a minority of patients include CAM in the treatment plan with
      curative intent. This review article focuses on practices belonging to the CAM
      domains of mind-body medicine, CAM botanicals, manipulative practices, and energy
      medicine, because they are widely used as complementary approaches to palliative
      cancer care and cancer symptom management. In the area of cancer symptom
      management, auricular acupuncture, therapeutic touch, and hypnosis may help to
      manage cancer pain. Music therapy, massage, and hypnosis may have an effect on
      anxiety, and both acupuncture and massage may have a therapeutic role in cancer
      fatigue. Acupuncture and selected botanicals may reduce chemotherapy-induced
      nausea and emesis, and hypnosis and guided imagery may be beneficial in
      anticipatory nausea and vomiting. Transcendental meditation and the mindfulness
      based stress reduction can play a role in the management of depressed mood and
      anxiety. Black cohosh and phytoestrogen-rich foods may reduce vasomotor symptoms
      in postmenopausal women. Most CAM approaches to the treatment of cancer are safe
      when used by a CAM practitioner experienced in the treatment of cancer patients.
      The potential for many commonly used botanical to interact with prescription
      drugs continues to be a concern. Botanicals should be used with caution by cancer
      patients and only under the guidance of an oncologist knowledgeable in their use.

PMID- 17034679
TI  - Recovery issues in cancer survivorship: a new challenge for supportive care.
AB  - The growing population of cancer survivors represents a clear challenge to
      clinicians and researchers to look beyond the search for a cure and to address
      the multifaceted needs of those living with and beyond a cancer diagnosis. Common
      sequelae that disrupt the psychosocial aspects of life for adult cancer survivors
      after primary treatment include: fatigue; cognitive changes; body image; sexual
      health and functioning; infertility; fear of recurrence; PTSD and stress
      syndromes; family/caregiver distress; socioeconomic issues; and distress,
      anxiety, and depression. Psychosocial interventions, particularly group-based
      interventions and physical activity programs, have shown great promise in
      improving these outcomes. Future research will identify even better targeted,
      more efficacious, and more cost effective programs and disseminate them into
      cancer care settings. Healthcare providers must realize that they serve as vital
      gatekeepers to services that will help optimize cancer survivors' psychosocial as
      well as physical outcomes. Addressing these issues in the post-treatment period
      represents the new challenge to supportive care.

PMID- 17034680
TI  - New tools to fight disease should be celebrated, but we also need the systems and
      the people to deliver them.

PMID- 17034682
TI  - Surgical collaboration between rich and poor - what does the future hold?

PMID- 17034683
TI  - College of Surgeons of East, Central and Southern Africa.

PMID- 17034684
TI  - Management of hydrocephalus.

PMID- 17034685
TI  - The acute abdomen and HIV.
AB  - HIV-related disease continues to increase and presents the greatest single
      challenge to the medical practitioner seeking to alleviate suffering in the
      developing world. As a result, the practice of surgery cannot ignore the impact
      of HIV and must assess the implications of this new disease. Although much has
      been written of HIV-related surgical pathology, the preponderance of the
      literature reflects the experience of surgeons working in well-equipped hospitals
      in the First World where HIV prevalence is low and where there is ready access to
      a multiplicity of drug therapies and nursing backup.

PMID- 17034686
TI  - Sickle cell disease in surgery.

PMID- 17034687
TI  - Fournier gangrene.
AB  - Fournier gangrene is a necrotizing infection involving the soft tissues of the
      male genitalia. It was first described in 1764 by Baurienne and given its
      eponymous name after Jean-Alfred Fournier in 1883 presented a case of perineal
      gangrene in an otherwise healthy young man. While only 600 cases of Fournier
      gangrene have been reported in the world literature since 1996, it is a common
      and serious disease in Africa. In Maputo Central Hospital alone, between 12 and
      16 cases are admitted every year and treated with a 20% mortality. The typical
      patient is an elderly male in his sixth or seventh decade with co-morbid
      diseases. While considered to affect males only, a similar condition may
      occasionally affect the female genitalia.

PMID- 17034688
TI  - Postpartum care attendance at a rural district hospital in Zambia.
AB  - Postpartum care is an important tool in both preventive and promotive maternal
      health care. We studied the postpartum care attendance rate in 540 women who
      delivered at a district hospital in Zambia. Forty-two percent of the women
      attended postpartum care within six weeks of delivery. Women who did not come for
      postpartum care were older and had to travel more hours to the hospital than
      women who attended postpartum care. The low postpartum care attendance rate could
      be increased if health workers provided mother and child health care in an
      integrated way and were aware that recently delivered women also visit the
      hospital for reasons other than postpartum care. Health workers need to inform
      pregnant women about the benefits of postpartum care and make them feel welcome
      to attend this health service, also when women decide to deliver at home.

PMID- 17034689
TI  - HIV awareness and traditional birth practice in the Niger delta area of Nigeria.

PMID- 17034690
TI  - The neurodevelopmental abilities of very-low-birthweight children in Trinidad,
      West Indies.
AB  - Neurodevelopmental abilities of 33 very-low-birthweight (VLBW) Trinidadian
      children and randomly selected matched pairs of classmates who were of normal
      birth weight were tested in 1998 at ages 68-88 months, using the McCarthy Scales
      of Children's Abilities. The 1 min Apgar score was significantly lower in the
      VLBW children, 6.5 (SD 1.0) versus 7.7 (SD 1.27), P<or=0.001. Mean scores on the
      McCarthy Scales for study and control children were: (Table cannot be
      represented.) These differences may reflect a delay in the neurodevelopment of
      these children. However, the effect of child-rearing practices and the
      inappropriateness of the test for the population cannot be ruled out.

PMID- 17034692
TI  - Hospital biohazard control: low-cost device for safe collection and disposal of
      hypodermic needles.
AB  - This paper describes experience with a low-cost initiative for safe collection
      and disposal of hypodermic needles in health facilities in developing countries.
      Produced locally, a purpose-made container for collecting 500-1000 used
      hypodermic needles should cost no more than 20-50 US cents. Trial in our
      immunization clinic and injection room for the last year has shown its potential
      for injection safety generally and particularly during immunization campaigns.

PMID- 17034691
TI  - Evaluation of tests for serological diagnosis of scrub typhus.
AB  - Two specific serological tests, a Dot enzyme immunoassay (EIA) and an
      immunoglobulin (Ig)M enzyme-linked immunosorbent assay (ELISA) using the 56 kDa
      antigen and the Weil-Felix test were evaluated for diagnosis of scrub typhus.
      Sensitivity of 100, 86.5 and 43.5% were observed with Dot EIA, IgM ELISA and Weil
      Felix test, respectively. False-positive reactions were observed in patients with
      falciparum malaria, pulmonary tuberculosis, S. viridans septicemia and typhoid
      fever using Dot EIA and IgM ELISA. Therefore, although Dot EIA and IgM ELISA are
      useful in the serodiagnosis of scrub typhus, efforts should be made to rule out
      other febrile illnesses.

PMID- 17034693
TI  - Improvised rigid oesophagoscope.

PMID- 17034694
TI  - Development of an indigenous paediatric crash cart based on the ABC of
      resuscitation.

PMID- 17034695
TI  - The increasing prevalence of diabetic nephropathy as a cause of end stage renal
      disease in Nigeria.
AB  - The incidence of diabetic nephropathy, the leading cause of chronic kidney
      disease in the western world has increased by 150% in the past 10 years in the
      United States, with similar trends in Europe and Japan. It is apparent from the
      present study that diabetic nephropathy may be assuming an increasing role as a
      cause of chronic kidney disease in Nigeria.

PMID- 17034697
TI  - Endemic fluorosis in an isolated village in western Maharashtra, India.
AB  - We surveyed 76 residents of a small village in Mahad Taluka, where the first
      index case of dental fluorosis was detected. Thirty-three (43.42%) cases of
      dental fluorosis were identified. The source of drinking water was a bore well
      with a fluoride content of 5.37 parts per million.

PMID- 17034696
TI  - Skin disorders among school children in rural Tanzania and an assessment of
      therapeutic needs.
AB  - Eight hundred and twenty primary school children were examined to assess the
      spectrum and prevalence of skin diseases in rural Tanzania. In all, 55% of the
      children had one or several skin disorders, but only 33% of all diagnoses in a
      cluster of 14% of the children required treatment. Tinea versicolor was found in
      26.2%, pyoderma and dermatophytoses in less than 10%, while few children had
      scabies or eczematous lesions.

PMID- 17034698
TI  - Knowledge, attitudes and public health response towards plague in Petauke,
      Zambia.
AB  - In 2001, two plague outbreaks were reported in Zambia, one of which occurred in
      Petauke, Eastern Province, resulting in high morbidity and mortality. Of the
      community respondents, 43.4% did not know the aetiology of plague. Although rats
      and fleas were frequently mentioned, many respondents did not know how these were
      related to plague. Local belief that the plague outbreak was the result of
      witchcraft was prevalent. Use of rodenticides was not preferred as these were
      reports of they being used for poisoning people. The public health response was
      initially slow by both the community and also the formal health sector. Once the
      diagnosis of plague was made, fears of witchcraft dispelled and collaboration not
      only between the formal health sector and the community, but also between Zambian
      health workers and their Mozambican counterparts developed, and it was possible
      to control the outbreak.

PMID- 17034699
TI  - Clinical and echocardiographic study of hypertrophic cardiomyopathy in Tanzania.
AB  - There are few published reports of hypertrophic cardiomyopathy (HCM) in Africans,
      partly due to lack of Echocardiography machines at most hospitals. Among 6680
      patients referred for echocardiography at Muhimbili National Hospital between
      June 1998 and October 2002, 134 (0.19%) patients had HCM. Their mean age was
      54.8+/-14.2 years. In total 67.9% were men and 32.1% were women. Due to the
      diverse clinical features only eight (5.9%) patients had a correct diagnosis of
      HCM prior to their ECHO. The important role of echocardiography in the diagnosis
      of HCM is stressed with a plea for the increasing availability of this non
      invasive technique for early and accurate diagnosis.

PMID- 17034700
TI  - Blood transfusion in an emergency paediatric unit in Owerri, Nigeria: pattern and
      outcome.
AB  - The increasing number of patients presenting with severe anaemia and who
      invariably receive blood transfusion is of concern. This retrospective study
      reports the pattern of presentation and the outcome of management of patients who
      were transfused in the Emergency Paediatric Unit of Federal Medical Centre,
      Owerri, between September 2002 and August 2004.

PMID- 17034701
TI  - Hepatic histopathological findings in HIV patients at postmortem in Jos
      university teaching hospital, Nigeria.
AB  - Multi-organ involvement by opportunistic infections and neoplasms is the major
      cause of morbidity and mortality in people living with HIV/AIDS. We determined
      the spectrum/frequency of hepatic histopathological lesions in a prospective
      study of postmortem liver biopsies from 100 patients (50 females and 50 males,
      age range 18-55 years) who died from HIV/AIDS in Jos university teaching
      hospital, Nigeria. The majority of the patients, 65 (65%), had clinical
      tuberculosis. Granulomatous hepatitis, chronic hepatitis, non-specific reactive
      hepatitis (NSRH) and steatosis were the commonest hepatic histopathologic lesions
      occurring in 34, 20,15 and 12% of patients, respectively. Seven (7%) had normal
      histological features. This study shows that the liver is affected in HIV/AIDS as
      reported elsewhere in the world. Therefore, liver biopsy in HIV patients may be
      helpful in the management of these patients.

PMID- 17034702
TI  - Penile cancer associated with so-called low-risk human papilloma virus. Report of
      five cases from rural Venezuela.
AB  - Penile cancer is uncommon in western countries. It has been related to human
      papilloma virus (HPV) types 16 and 18. We describe five cases of carcinoma of the
      penis in men from a rural Venezuelan town that were related to HPV types 6, 11,
      53, which represent a rather low risk for cancer.

PMID- 17034703
TI  - Infection rate in closed fractures after internal fixations in a municipal
      hospital in Ghana.
AB  - This prospective study conducted in the Holy Family Municipal Hospital in
      Techiman, Ghana aimed to determine the incidence of wound infection following
      internal fixation of closed fractures in a municipal hospital in a developing
      country. Between May 2000 and February 2005, 194 patients were treated for closed
      fractures, implanting a total of 215 internal fixations. Patients were reviewed
      10, 30 and 120 days after operation. In 141 (73%) patients, a follow-up of four
      months was achieved. Of all patients, six developed an infection, two deep and
      four superficial. The cumulative incidence of wound infection after internal
      fixation was 3.3%. This study demonstrates that the incidence of wound infection
      following internal fixation is comparable with hospitals in a temperate climate
      in industrialized countries. We therefore conclude that specific tropical risk
      factors play a minimal role in the development of wound infection.

PMID- 17034704
TI  - Gynaecologic mortality in Enugu, Nigeria.
AB  - A retrospective review of 79 deaths in 2033 gynaecologic admissions at a referral
      centre showed that the leading causes of mortality were cervical cancer,
      choriocarcinoma, septic abortion and ovarian cancer, in that order. The results
      suggest a need for an organized cancer programme to limit morbidity and mortality
      from malignant disease of the female genital tract.

PMID- 17034705
TI  - Accuracy and cost-benefit of pooled versus singleton screening blood donations
      for anti-HIV: impact on different blood bank set-ups.
AB  - This study evaluates the accuracy and cost-benefit of implementing a pooled
      screening procedure in blood banks in general and especially in developing
      countries. The sensitivity of pooled testing was found to be relatively high,
      with the lowest levels estimated at about 98% for pools consisting of three, six,
      and 12 samples. Screening in pools of up to 12 samples is expected to be
      economically beneficial in countries with HIV prevalence rates of 8-10%, which
      cannot afford the cost of care for an HIV-infected patient.

PMID- 17034706
TI  - Recurrent tumoral calcinosis.
AB  - Tumoral calcinosis is a rare, benign disease that commonly affects the African
      blacks. We report on a 20-year-old Nigerian presenting with recurrent multiple
      subcutaneous masses around the scapular, elbow, hip and gluteal regions. The X
      rays, fine needle aspiration cytology and tissue biopsy confirmed the diagnosis
      and the patient had a successful excision with good healing.

PMID- 17034707
TI  - Case series of acute presentation of abdominal TB in Ghana.
AB  - We report on a six-year prospective study to determine the presentation and
      outcome of acute abdominal TB at Komfo Anokye Teaching Hospital. Between January
      1998 and December 2003, material for biopsy including resected bowel was taken
      from all cases of acute abdomen, which at laparotomy were suspected as one or
      other form of abdominal TB. TB-positive cases were then retrospectively analysed
      for clinical presentation and outcome of surgical treatment. There were 96
      histologically proven cases of abdominal TB, 60 in women and 36 in men. Seventy
      patients (72.9%) were admitted as acute intestinal obstruction with acute
      abdominal pain, vomiting, constipation, distension and fluid levels on abdominal
      X-ray. Twenty-two (22.9%) patients were admitted as acute diffused peritonitis -
      with generalized abdominal tenderness, guarding and rebound - and four (4.2%) as
      acute appendicitis. There were 74 emergency bowel resections (77% resection rate)
      for 34 ileocaecal masses, 16 strictures, 10 perforations and 14 adhesions, with a
      mortality of 4.2%. Previous series from our subregion have reported similar
      emergency resection mortality rates for other abdominal conditions. All the
      patients received postoperative anti-TB therapy. This paper notes that acute
      intestinal obstruction is the most common acute presentation of abdominal TB in
      our environment. The results of emergency resection compare favourably with
      resection for other acute abdominal conditions.

PMID- 17034708
TI  - Isolated renal and retroperitoneal hydatid cysts: a report of 23 cases.
AB  - Isolated extrarenal retroperitoneal and renal echinococcal cysts are rare
      manifestations of hydatid disease. We report 23 cases of renal and other
      retroperitoneal hydatid cysts diagnosed and treated in our clinic. Flank pain,
      abdominal mass and non-specific symptoms such as nausea and vomiting were the
      major symptoms. Indirect haemagglutination test was positive in 18 cases and
      eosinophilia in four cases. Among imaging studies computerized tomography was the
      most valuable diagnostic examination. A high index of suspicion is needed for
      preoperative diagnosis of hydatid disease of kidney and retroperitoneum.

PMID- 17034709
TI  - Psoas abscess in children: making the diagnosis.

PMID- 17034710
TI  - An unusual presentation of hepatitis A virus infection: Guillain-Barre syndrome.

PMID- 17034711
TI  - Cryptococcal peritonitis as the first AIDS-defining illness in Zimbabwe.

PMID- 17034712
TI  - African histoplasmosis - masquerading as a malignant bone tumour.
AB  - A 23-year-old immunocompetent woman presented with a two-month history of
      fungating left shoulder and left elbow swellings associated with fever, weight
      loss and anaemia. X-rays showed lytic destruction of the lateral third of the
      left clavicle and distal half of the left humerus. Histology of biopsy specimen
      confirmed African histoplasmosis. The lesion resolved following treatment with
      ketoconazole.

PMID- 17034713
TI  - Fever of unknown origin in North Jordan.
AB  - This is a retrospective study of all patients admitted to Basma Teaching Hospital
      with a diagnosis of fever of unknown origin (FUO). The study took place from
      January 1995 to December 2001. Fifty-two patients fulfilled the criteria of FUO.
      Infections were responsible for 26 cases (50%), malignancy for eight cases (15%),
      connective tissue disorder for six cases (12%) and others for 12 cases (23%).
      Infections remain the most common causes of FUO in Jordan, mainly tuberculosis,
      brucellosis and typhoid fever.

PMID- 17034714
TI  - Exudative pleural effusion due to brucellosis in a patient with chronic
      obstructive pulmonary disease.
AB  - Pleural involvement is a rare presentation of brucellosis. We report a patient
      referred for the evaluation of fever, right-sided pleural effusion and hilar
      lymph node enlargement. The pleural fluid revealed exudative characteristics with
      the predominance of neutrophils. Brucella melitensis was isolated from bone
      marrow, pleural effusion and blood cultures. The diagnosis was also confirmed by
      demonstration of a high Brucella agglutinin titre. The patient was successfully
      treated with rifampicin and doxicycline for three months.

PMID- 17034715
TI  - Syringomyelia: an early complication of tuberculous meningitis.

PMID- 17034716
TI  - Pattern of paediatric renal disease in inpatients in Calabar, Nigeria.
AB  - A 10-year retrospective review of inpatients in Calabar showed that of 5641
      children admitted,182 (3.2%) had renal disease. The major lesions were acute
      glomerulonephritis (36.9%) and nephrotic syndrome (30.7%), while less common ones
      included urinary tract infection (8.9%), obstructive uropathy, acute renal
      failure (6.7%, each) and nephroblastoma (6.2%).

PMID- 17034717
TI  - Assault-related eye injuries in Enugu, Nigeria.

PMID- 17034718
TI  - [Research advances and perspectives of prevention and control of pneumoconiosis].

PMID- 17034719
TI  - [Inhibition of N-acetyl-L-cysteine on expressions of matrix metalloproteinases
      increased by exposure to silicon dioxide in lung fibroblasts in rats].
AB  - OBJECTIVE: To explore the effect of N-acetyl L-cysteine (NAC) on expressions of
      matrix metalloproteinases-2, 9 (MMP-2, MMP-9) in lung fibroblasts of SiO(2)
      exposed rats. METHODS: Seventy-five Wistar rats were divided randomly into three
      groups. The control group was administered with normal Saline. The model group
      and the interventional group were administered with SiO(2), and the
      interventional group was administered with NAC before SiO(2) was administered.
      Lung fibroblasts were isolated on day 1, 3, 7, 14, 28 after exposure to SiO(2).
      The expressions of MMP-2 and MMP-9 were evaluated by Immunocytochemistry and RT
      PCR. RESULTS: (1) The expressions of protein and mRNA of MMP-2 in the model group
      were higher than that in the control group on all days after exposure to SiO(2)
      (P < 0.01). The expression of protein of MMP-9 was higher than the control group
      on day 1, 3, 7, and mRNA was higher on day 1, 3 (P < 0.01). (2) The expression of
      protein of MMP-2 in the interventional group was lower than the model group on
      all days, higher than the control group on day 3, 7, 14, 28, and the expression
      of mRNA was higher than the control group, lower than the model group, on all
      days (P < 0.05 or P < 0.01). The expression of protein of MMP-9 in the
      interventional group was lower than the model group on day 1, 3, 7, but higher
      than the control group on day 3, 7, and mRNA was lower than the model group on
      days 1, 3, higher than the control group (P < 0.05). CONCLUSION: NAC inhibits the
      expressions of MMP-2, MMP-9 in lung fibroblasts.

PMID- 17034721
TI  - [Expression and role of nuclear transcription factor Sp1 in macrophages
      stimulated by silicon dioxide].
AB  - OBJECTIVE: To study the expression and localization of nuclear transcription
      factor Sp1 in macrophages after stimulated by silicon dioxide in vivo and in
      vitro. METHODS: Forty Sprague Dawley rats were randomly divided into the control
      group and the silica exposure group, 20 in each group. The rat silicosis models
      were established by direct tracheal instillation of silica into rat lung (0.2
      g/kg) only once while the control group was instilled with equal amount of
      saline. Animals were killed at 1st, 7th, 14th, 21st and 28th day after
      instillation. Dynamic changes of Sp1 protein expression and its cellular
      localization were detected by immunohistochemistry in pulmonary macrophages. In
      vitro, Sp1 mRNA and protein expression and their dynamic changes were monitored
      by RT-PCR and western blotting after stimulated by silicon dioxide in cultured
      RAW264.7 macrophages respectively. Cellular localization of Sp1 protein was
      characterized by immunocytochemistry. RESULTS: Compared to the control group, the
      Sp1 protein expression was increased in pulmonary macrophages and reached the
      peak at the 14th day in the silica exposure group. In vitro, the Sp1 mRNA level
      began to rise at 30 minutes after the administration of silicon dioxide and
      reached the peak at 240 minutes and then decreased to the minimal level at 960
      minutes. The Sp1 total protein and nuclear protein also exhibited the similar
      trend. The former reached the peak at 240 minutes and the latter at 480 minutes.
      The significant nuclear translocation of Sp1 protein was observed at 120 minutes
      after the administration of silicon dioxide and became most significant at 480
      minutes. CONCLUSION: Silicon dioxide can activate nuclear transcription factor
      Sp1 in macrophages in vivo and in vitro. Sp1 might play an important pathogenic
      role in the development of silicosis.

PMID- 17034723
TI  - [Effects of silicon dioxide on expression of alpha-smooth muscle actin in human
      lung fibroblasts].
AB  - OBJECTIVE: To investigate the effects of SiO(2) on the expression of alpha-smooth
      muscle actin (alpha-SMA) in human lung fibroblasts in vitro and vivo. METHODS:
      The experimental group comprised 32 rats while 32 rats were included in the
      control. In vivo, the expression of alpha-SMA in lung tissues of rats exposed to
      SiO(2), the supernate of RAW264.7 cells, SiO(2) and the growth factor beta(1)
      (TGF-beta(1)) were investigated, respectively. RESULTS: (1) alpha-SMA positive
      myofibroblasts appeared in the lung tissues of the 28th day groups exposed to
      SiO(2). (2) The expression of alpha-SMA in HLF-02 cells was unregulated by TGF
      beta(1) and supernate of RAW264.7 cells exposed to SiO(2). (3) The expression of
      alpha-SMA in HLF-02 cells was not induced by SiO(2). CONCLUSION: Myofibroblasts
      related to silicosis, and the appearance of myofibroblasts (in vitro) are
      independent on direct stimulation by SiO(2), but related to the mediator (TGF
      beta(1)) secreted by SiO(2) stimulated macrophages.

PMID- 17034724
TI  - [Relationship between polymorphism of interleukin-1 and pneumoconiosis
      susceptibility].
AB  - OBJECTIVE: To explore the relationship between the polymorphism of Interleukin-1
      and the pneumoconiosis susceptibility. METHODS: Eighty patients with silicosis
      and 45 with coal workers' pneumoconiosis (CWP) were selected while 125 male
      workers, Han nationality in the same workplace as the patients were selected as
      the controls. Between the patients and the control, the differences of age and
      cumulative length of service were less than five years and two years,
      respectively. The controls were exposed to dusts but did not suffer from
      pneumoconiosis. Moreover, the patients and the controls were paired by 1:1. DNA
      was extracted from leucocytes by the hydroxybenzene chloroform method. The
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      techniques and PCR were used to examine polymorphism of IL-1alpha (-889), IL
      1beta (-511) and IL-1Ra (+2018) and variable number of tandem repeats (VNTR) of
      IL-1Ra. After the preliminary experiment, the most adaptive PCR reaction, the
      restriction enzyme digest and electrophoresis system were used. RESULTS: The
      difference in IL-1alpha (-889) 1/2 + 2/2 between the pneumoconiosis patients and
      the controls was significant (P < 0.01). The result of conditional Logistic
      regression showed that heterozygote and allele 2 of IL-1a (-889) were risk
      factors of pneumoconiosis. The difference in the genotype frequencies of IL-1beta
      (-511) 1/2 + 2/2, IL-1Ra (+2018) 1/2 + 2/2 and IL-Ra VNTR1/2 + 2/2 between the
      patients and the controls were not statistically significant (P > 0.05).
      CONCLUSION: IL-1alpha (-889) gene polymorphism is related to pneumoconiosis.
      Workers with IL-1alpha (-889) allele 2 are susceptible to the pneumoconiosis. The
      relationship between IL-1beta (-511), IL-1Ra (+2018), IL-1Ra VNTR genes
      polymorphisms and pneumoconiosis are not found.

PMID- 17034725
TI  - [Application of double-level non-invasive positive ventilation in rehabilitation
      of patients with coal workers' pneumoconiosis].

PMID- 17034726
TI  - [Relationship between single nucleotide polymorphisms of NRAMP1 gene and
      susceptibility to pulmonary tuberculosis in workers exposed to silica dusts].
AB  - OBJECTIVE: To explore the relationship between polymorphisms of natural
      resistance-associated macrophage protein 1 (NRAMP1) gene and genetic
      susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica
      dusts. METHODS: A 1:2 case control study of 61 male workers with PTB (50
      silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB
      free workers (100 silicosis patients and 22 unsilicosis workers) as the control
      group was conducted with the frequency matched for age of +/- 5 years, the job,
      the silica exposure, and the condition of cigarette smoking and alcohol drinking.
      The polymerase chain reaction-restrained fragment length polymorphism technique
      (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of
      NRAMP1 INT4 and D543N. RESULTS: There was a 2.73 times (95% CI: 1.32
      approximately 5.64) increased risk of silicosis for individuals with C allele of
      NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of
      NRAMP1 D543N was not associated with PTB (P > 0.05). CONCLUSION: The G > C
      mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for
      the workers exposed to PTB.

PMID- 17034727
TI  - [Relationship between genetic polymorphism of interleukin-6 and pneumoconiosis].
AB  - OBJECTIVE: To explore the relationship between interleukin-6 (IL-6) (-634C/G)
      genetic polymorphisms and the pneumoconiosis. METHODS: A total of 104 male stage
      I pneumoconiosis patients diagnosed by the Pneumoconiosis Diagnosis Expert Panel
      according to the Chinese National Diagnosis Criteria of Pneumoconiosis (GBZ 70 -
      2002) were selected. The pneumoconiosis comprised 66 silicosis and 38 coal
      worker' pneumoconiosis (CWP). A total of 122 workers exposed to same dusts as the
      patients but without pneumoconiosis including 77 exposed to silica dusts and 45
      to coal dusts were selected. The patients and the controls had the same dust
      exposure history. The peripheral venous blood was drawn from each subject. The IL
      6 (-634C/G) genetic polymorphisms were detected by polymerase chain reaction
      restriction fragment length polymorphisms (PCR-RFLP) techniques. RESULTS: The
      frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes were 66.7%, 19.7% and
      13.6% in silicosis group, 42.9%, 42.9% and 14.2% in silica dust exposure group,
      73.7%, 18.4% and 7.9% in CWP group, 51.1%, 35.6% and 13.3% in coal dust exposure
      group respectively. The statistical analysis indicated that there was significant
      difference in the frequencies of IL-6 (-634C/G) (CC, CG and GG) genotypes between
      silicosis patients and workers exposed to silica dusts (P < 0.05). CONCLUSION: IL
      6 (-634 C/G) genetic polymorphisms might play a role in the occurrence of
      silicosis.

PMID- 17034728
TI  - [Determination and analysis of silica particles surface alumino-silicate
      occlusion].
AB  - OBJECTIVE: To investigate the methods of determining aluminum silicate coated on
      the surface of silica particles and analyze the role of surface occlusion on
      development of silicosis. METHODS: Respirable dust samples were collected on
      filters using 2 L/min flow in tungsten mines and pottery factories of Jiangxi
      province, and tin mines of Guanxi province. Dust particles were analyzed by a
      multiple-voltage scanning electron microscopy-energy dispersive X-ray
      spectroscopy (MVSEM-EDS) using 20 KeV and 5 KeV electron beam accelerating
      voltages. Changes in the silicon to aluminum X-ray line intensity ratio between
      the two voltages are compared particle by particle. This provided an index that
      distinguishes a silica particle that was homogeneously aluminum-contaminated from
      a clay coated silica particle. RESULTS: The total of 3,982 dust particles from 47
      dust samples of seven pottery factories, three tin mines and three tungsten mines
      were analyzed in this study. Significant difference of aluminum silicate coated
      on the surface of silica particle was shown between particles from pottery
      factories and tin mines. The average sample percentage of respirbale-sized silica
      particles alumino-silicate occlusion in the pottery factories (45%) was higher
      than that in the tin mines (18%) and tungsten mines (13%). CONCLUSION: Higher
      percentages silica particles alumino-silicate occlusion is observed in the
      pottery factories than that in metal mines. These surface analysis results help
      to understand differences in risk of silicosis when exposure is normalized to
      cumulative respirable surface silica dust.

PMID- 17034729
TI  - [Relationship between dust exposure and chronic obstructive pulmonary diseases
      and heat shock protein 72 and 73 in lymphocytes among coal miners].
AB  - OBJECTIVE: To assess the expression of Hsp72 and Hsp73 in chronic obstructive
      pulmonary disease (COPD) and to evaluate their roles in damage from coal dust
      exposure. METHODS: A case control study of 50 coal miners suffering from COPD and
      50 healthy coal miners were selected from one coal mine. The levels of Hsp72 and
      Hsp73 in peripheral blood lymphocytes were determined by flow cytometry for all
      subjects. RESULTS: (1) The expression of basic Hsp72 of peripheral blood
      lymphocytes for patients and controls was not different from that inducible
      expressed Hsp72 by 42 degrees C heat stress or by BPDE exposure. (2) The
      expression of Hsp72 in COPD patients (17.7 +/- 4.9) was significantly lower than
      that in healthy coal miners (22.6 +/- 10.0) (P < 0.01). On the other hand, the
      expression of Hsp73 in COPD patients (33.5 +/- 11.7) was higher than that in
      healthy coal miners (19.6 +/- 5.9) (P < 0.01). (3) A-positive relationship
      between the expression of Hsp72 and cumulative inhaling coal dust exposure was
      observed. No relationship was found between Hsp73 and cumulative inhaling coal
      dust exposure. CONCLUSION: The decreased expressions of Hsp72 in peripheral blood
      lymphocytes of COPD coal miners.

PMID- 17034730
TI  - [Effects of taurine on type I and III collagen expression in rats lung exposed to
      silica].
AB  - OBJECTIVE: To evaluate the effects of taurine in diet on the expression of type I
      and III collagen and collagen ratio at different time points in rats lung by
      image process technology. METHODS: Wistar rats were randomly divided into three
      groups: the saline instilled with a control diet (the saline treated group);
      silica instilled with a control diet (the silica treated group); and silica
      instilled with a diet containing 2.5% taurine (the taurine treated group). Animal
      models were established by the direct tracheal instillation of silica into rat
      lungs exposed surgically. The taurine concentration of serum was analyzed by
      means of HPLC. Paraffin embedded lung sections were stained with Sirius red.
      Polarization microscopy and Image Pro Plus Version 4.5 for windows were used for
      detecting type I and III collagen. RESULTS: The concentration of taurine in serum
      of the taurine treated group was significantly elevated compared to the saline
      treated and silica treated group (P < 0.05 or P < 0.01). Sirius red polarization
      microscopy showed that type I and III collagen positive area percentage were
      elevated in the silica treated rats compared with the saline treated group. On
      the 7th, 14th, 21st, 28th day after silica instillation type I collagen positive
      area percentage was increased by 3.84, 3.77, 3.73, 9.83 respectively (P < 0.01),
      and type III collagen positive area percentage were elevated by a little in the
      silica treated rats compared with saline treated group. The taurine treatment
      significantly decreased elevation of silica type I collagen positive area
      percentage of lung by 2.39, 1.62, 7.13 at the 7th, 21st, 28th day respectively (P
      < 0.05 or P < 0.01), and type III collagen positive area percentage of lung by
      2.62 at the 28th day (P < 0.05) compared with the silica treated group. The ratio
      of type I to III collagen was increased from the 7th day to 28th day after silica
      instillation, and reached 1.87 at the 28th day with the maximal ratio in the
      silica-treated group. CONCLUSION: Treatment with taurine can effectively
      attenuate type I and III collagen expression in the rat lung induced by silica
      particles at different time points in our study.

PMID- 17034731
TI  - [Effects of dusts on workers' health in enzyme production plants].
AB  - OBJECTIVE: To assess the health effects of dusts in enzyme production plants.
      METHODS: The concentration of enzyme-containing dusts, the enzyme and the wheat
      containing dusts and their health effects on workers were investigated in three
      enzyme production plants. Air samples were collected by high volume sampler and
      personal sampler. Total dust was weighed and its content of enzyme was analyzed
      by enzyme activity method. Health effects were assessed by the questionnaire, the
      pulmonary function and the skin prick test. RESULTS: It was found that the
      geometric mean of enzyme-containing dust was 8.91 mg/m(3), the industrial enzyme
      was 1.68 mg/m(3), and the wheat-containing dust was 6.93 mg/m(3). The enzyme
      containing dust higher than 20 mg/m(3) caused eye symptoms. The wheat-containing
      dust at 6.93 mg/m(3) might result in skin and nose symptoms. The sensitization
      could be observed in enzyme and wheat exposed workers. CONCLUSION: Adverse
      effects may arise for the health of the workers if the concentration of enzyme
      containing dusts and the wheat-containing dusts is up to a certain limit and it
      is necessary to make the limit of these indexes.

PMID- 17034732
TI  - [Investigation on psychological health of workers in a steel factory].

PMID- 17034733
TI  - [Dynamic analysis of dusts in Rush-mat industries].

PMID- 17034734
TI  - [Effects of professional exposure to medicinal chemicals on women's health].

PMID- 17034735
TI  - [Preliminary research on effects of subchronic exposure to hydroxylammonium
      nitrate on tests germ cells of male rats].

PMID- 17034736
TI  - [Expression of lysozyme of macrophages of alveolus in rats exposed to quartz].

PMID- 17034737
TI  - [Research on detection of nodules in lungs with low-dosage multiple-layer CT
      maximal intensity projection].

PMID- 17034738
TI  - [Spiral CT in diagnosis of pneumoconiosis pulmonary heart disease in coal
      workers].

PMID- 17034739
TI  - [Relationship between pulmonary ventilation of patients with molybdenum silicosis
      and manifestation in chest X-ray].

PMID- 17034740
TI  - [Determination of sixteen types of polycyclic aromatic hydrocarbon in
      atmosphere].

PMID- 17034741
TI  - [Influential factors for determination of free silicon dioxide in dusts and
      improvement].

PMID- 17034742
TI  - [Advance of research on p53 gene and regulation of DNA injury signals].

PMID- 17034743
TI  - [Health proclamation of workers].

PMID- 17034744
TI  - [Occupational health and medical surveillance principles for workers exposed to
      silicon dusts in metal industry of Germany].

PMID- 17034745
TI  - [Discussion on revision of exposure limits of quartz dusts in mining and
      quarrying industries in Spain].

PMID- 17034746
TI  - [Quality control for evaluation of effect of control over occupational hazards in
      construction projects].

PMID- 17034747
TI  - Errors and violations in relation to motorcyclists' crash risk.
AB  - This study was conducted to: (a) develop a questionnaire that reliably measures
      the behaviour of motorcyclists and (b) test which types of behaviour predict
      motorcyclists' crash risk. A Motorcycle Rider Behaviour Questionnaire (MRBQ),
      consisting of 43 items to measure the self-reported frequency of specific riding
      behaviours, was developed and administered to a sample of motorcyclists (N=8666).
      Principal components analysis revealed a 5-factor solution (traffic errors,
      control errors, speed violations, performance of stunts and use of safety
      equipment). Generalised linear modelling showed that, while controlling for the
      effects of age, experience and annual mileage, traffic errors were the main
      predictors of crash risk. For crashes in which respondents accepted some degree
      of blame, control errors and speed violations were also significant predictors of
      crash risk. Implications of the findings are discussed in relation to deciding
      which countermeasures may be most effective at reducing motorcycle casualty
      rates.

PMID- 17034748
TI  - The prevalence of, and factors associated with, serious crashes involving a
      distracting activity.
AB  - The study's objectives were to determine the prevalence and types of distracting
      activities involved in serious crashes, and to explore the factors associated
      with such crashes. We interviewed 1367 drivers who attended hospital in Perth,
      Western Australia between April 2002 and July 2004 following a crash. A
      structured questionnaire was administered to each driver and supplementary data
      were collected from ambulance and medical records. Over 30% of drivers (433,
      31.7%) cited at least one distracting activity at the time of crashing and driver
      distraction was reported to have contributed to 13.6% of all crashes. The major
      distracting activities were conversing with passengers (155, 11.3%), lack of
      concentration (148, 10.8%) and outside factors (121, 8.9%). Using logistic
      regression, a distracting activity at the time of a crash was significantly more
      likely among drivers with shorter driving experience (0-9 years, 38.3% versus
      >or=30 years, 21.0%, p<0.001). Distracting activities at the time of serious
      crashes are common and can cause crashes, and the types of activities reported
      are varied. Increased driver awareness of the adverse consequences of distracted
      driving with a focus on novice drivers, enforcement of existing laws (e.g. those
      requiring a driver to maintain proper control of a vehicle), and progress on
      engineering initiatives (such as collision warning systems) are needed to reduce
      injury.

PMID- 17034749
TI  - Mobile phone use while driving in a sample of Spanish university workers.
AB  - A number of epidemiological studies have reported drivers who use a mobile phone
      while driving have an elevated risk of being involved in a crash. This is
      particularly concerning as a survey of drivers in the Spanish region of Catalunya
      found that approximately 87% own mobile phones. The present study investigated
      the reported frequency of mobile phone use on Spanish roads (for talking and
      using SMS), the characteristics of the drivers who use mobile phones while
      driving and whether they altered their driving behaviour when using a mobile
      phone. The research found that more than 60% use a mobile phone while driving and
      that the phone is mostly used for making calls, rather than using SMS. In
      general, males and females use mobile phones about the same reported frequency,
      although males were more likely to use a mobile phone to talk on the highway. The
      pattern for age was the same for both male and female participants, with the
      younger drivers using SMS more frequently than older drivers. On urban roads
      almost half of the drivers reported changing their driving behaviour when using a
      mobile phone, while on the highway this figure was slightly over 41%. The
      reported frequency of using a mobile phone to talk on urban roads was
      significantly correlated with crash involvement. However, this affect disappeared
      once the contributions of the demographic and descriptive variables had been
      partialled out.

PMID- 17034750
TI  - Magazine information on safety belt use for pregnant women and young children.
AB  - To assess the information on safety belt use for pregnant women and infants in
      maternity and baby magazines, we reviewed 2003 issues of the three top-selling
      monthly baby and maternity magazines. Articles on safety belt use during
      pregnancy and child safety seat (CSS) use for infants, and advertisements of the
      CSS, automobiles, or CSS-related products were examined for their informational
      content. Of the 9418 pages in the maternity magazines, 46 pages were on infants,
      16 pages on pregnant women and 162 pages displayed advertisements. Of the 9750
      pages in the baby magazines, 34 pages of articles addressed CSS use; no articles
      addressed the issue of pregnant women; 83 pages were advertisements. Although the
      magazines showed accurate information in general; its amount was not sufficient,
      and little specific information on appropriate use and selection of a CSS was
      seen. Some information was misleading and even incorrect: specifically related to
      when to start using a forward-facing seat, what products are attachable to the
      CSS, and the reuse of a CSS. Greater amounts and accuracy of safety information
      in these magazines would help pregnant women and parents acquire important safety
      knowledge that healthcare providers are falling short of providing in Japan.

PMID- 17034751
TI  - Protein array staining methods for undefined protein content, manufacturing
      quality control, and performance validation.
AB  - Methods to assess the quality and performance of protein microarrays fabricated
      from undefined protein content are required to elucidate slide-to-slide
      variability and interpolate resulting signal intensity values after an
      interaction assay. We therefore developed several simple total- and
      posttranslational modification-specific, on-chip staining methods to
      quantitatively assess the quality of gel element protein arrays manufactured with
      whole-cell lysate in vitro protein fractions derived from two-dimensional liquid
      phase fractionation (PF2D) technology. A linear dynamic range of at least 3 logs
      was observed for protein stains and immobilized protein content, with a lower
      limit of detection at 8 pg of protein per gel element with Deep Purple protein
      stain and a field-portable microarray imager. Data demonstrate the successful
      isolation, separation, transfer, and immobilization of putative transmembrane
      proteins from Yersinia pestis KIM D27 with the combined PF2D and gel element
      array method. Internal bovine serum albumin standard curves provided a method to
      assess on-chip PF2D transfer and quantify total protein immobilized per gel
      element. The basic PF2D array fabrication and quality assurance/quality control
      methods described here therefore provide a standard operating procedure and basis
      for developing whole-proteome arrays for interrogating host-pathogen
      interactions, independent of sequenced genomes, affinity tags, or a priori
      knowledge of target cell composition.

PMID- 17034752
TI  - Single DNA molecule stretching measures the activity of chemicals that target the
      HIV-1 nucleocapsid protein.
AB  - We develop a biophysical method for investigating chemical compounds that target
      the nucleic acid chaperone activity of HIV-1 nucleocapsid protein (NCp7). We used
      an optical tweezers instrument to stretch single lambda-DNA molecules through the
      helix-coil transition in the presence of NCp7 and various chemical compounds. The
      change in the helix-coil transition width induced by wild-type NCp7 and its zinc
      finger variants correlates with in vitro nucleic acid chaperone activity
      measurements and in vivo assays. The compound-NC interaction measured here
      reduces NCp7's capability to alter the transition width. Purified compounds from
      the NCI Diversity set, 119889, 119911, and 119913 reduce the chaperone activity
      of 5 nM NC in aqueous solution at 10, 25, and 100 nM concentrations respectively.
      Similarly, gallein reduced the activity of 4 nM NC at 100 nM concentration.
      Further analysis allows us to dissect the impact of each compound on both
      sequence-specific and non-sequence-specific DNA binding of NC, two of the main
      components of NC's nucleic acid chaperone activity. These results suggest that
      DNA stretching experiments can be used to screen chemical compounds targeting NC
      proteins and to further explore the mechanisms by which these compounds interact
      with NC and alter its nucleic acid chaperone activity.

PMID- 17034753
TI  - Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human
      bronchioepithelial cells.
AB  - High dose beta-carotene supplementation of smokers was associated with increased
      lung cancer risk in two intervention trials. It was proposed that generation of
      apocarotenals in smoke-exposed lungs impaired retinoic acid (RA) signaling,
      leading to squamous metaplasia and cell proliferation. To test this, we compared
      RA target gene regulation by retinoids, apocarotenals or beta-carotene by
      transcriptomics in BEAS-2B cells cultured to promote squamous differentiation.
      Retinoids, beta-carotene as well as apocarotenals induced known RA target genes.
      Retinoids upregulated involucrin, indicating that retinoids did not rescue BEAS
      2B cells from squamous differentiation. Muc5AC, a marker for mucous
      differentiation, was transiently induced. beta-Carotene and apocarotenals less
      strongly induced involucrin and did not induce muc5AC. In summary, apocarotenals
      or beta-carotene upregulated RA target genes suggesting promotion, not
      inhibition, of RA signaling in BEAS-2B cells. Furthermore, apocarotenals and beta
      carotene regulated gene expression independently of RA signaling. Squamous
      differentiation is not unequivocally linked to RA deficiency in BEAS-2B cells.

PMID- 17034754
TI  - Acclimation of mesophyll and bundle sheath chloroplasts of maize to different
      irradiances during growth.
AB  - The regulation by light of the photosynthetic apparatus, and composition of light
      harvesting complexes in mesophyll and bundle sheath chloroplasts was investigated
      in maize. Leaf chlorophyll content, level of plastoquinone, PSI and PSII
      activities and Lhc polypeptide compositions were determined in plants grown under
      high, moderate and low irradiances. Photochemical efficiency of PSII,
      photochemical fluorescence quenching and non-photochemical fluorescence quenching
      over a range of actinic irradiances were also determined, using chlorophyll a
      fluorescence analysis. Acclimation of plants to different light conditions caused
      marked changes in light-harvesting complexes, LHCI and LHCII, and antenna
      complexes were also reorganized in these types of chloroplasts. The level of
      LHCII increased in plants grown in low light, even in agranal bundle sheath
      chloroplasts where the amount of PSII was strongly reduced. Irradiance also
      affected LHCI complex and the number of structural polypeptides, in this complex,
      generally decreased in chloroplasts from plants grown under lower light.
      Surprisingly moderate and low irradiances during growth do not affect the light
      reaction and fluorescence parameters of plants but generated differences in
      composition of light-harvesting complexes in chloroplasts. On the other hand, the
      changes in photosynthetic apparatus in plants acclimated to high light, resulted
      in a higher efficiency of photosynthesis. Based on these observations we propose
      that light acclimation to high light in maize is tightly coordinated adjustment
      of light reaction components/activity in both mesophyll and bundle sheath
      chloroplasts. Acclimation is concerned with balancing light utilization and level
      of the content of LHC complexes differently in both types of chloroplasts.

PMID- 17034755
TI  - Spatial and temporal Ca2+, Mg2+, and ATP2- dynamics in cardiac dyads during
      calcium release.
AB  - We have constructed a three-dimensional reaction-diffusion model of the mammalian
      cardiac calcium release unit. We analyzed effects of diffusion coefficients,
      single channel current amplitude, density of RyR channels, and reaction kinetics
      of ATP(2-) with Ca(2+) and Mg(2+) ions on spatiotemporal concentration profiles
      of Ca(2+), Mg(2+), and ATP(2-) in the dyadic cleft during Ca(2+) release. The
      model revealed that Ca(2+) concentration gradients persist near RyRs in the
      steady state. Even with low number of open RyRs, peak [Ca(2+)] in the dyadic
      space reached values similar to estimates of luminal [Ca(2+)] in approximately 1
      ms, suggesting that during calcium release the Ca(2+) gradient moves from the
      cisternal membrane towards the boundary of the dyadic space with the cytosol. The
      released Ca(2+) bound to ATP(2-), and thus substantially decreased ATP(2-)
      concentration in the dyadic space. The released Ca(2+) could also replace Mg(2+)
      in its complex with ATP(2-) during first milliseconds of release if dissociation
      of MgATP was fast. The results suggest that concentration changes of Ca(2+),
      Mg(2+), and ATP(2-) might be large and fast enough to reduce dyadic RyR activity.
      Thus, under physiological conditions, termination of calcium release may be
      facilitated by the synergic effect of the construction and chemistry of mammalian
      cardiac dyads.

PMID- 17034756
TI  - Coexistence of two domains in intercellular lipid matrix of stratum corneum.
AB  - The outermost layer of the skin, the stratum corneum (SC), is composed of
      corneocytes and an intercellular lipid matrix. The matrix acts as both the main
      barrier and also as the pathway of water, drugs, etc. across the SC. In the
      mammalian SC, the longitudinal arrangement of the lipid molecules, consisting of
      long and short lamellar structures with repeat distances of about 13 nm and 6 nm,
      respectively, has been observed by small-angle X-ray diffraction. In the lateral
      arrangement of the lipid molecules, hexagonal and orthorhombic hydrocarbon-chain
      packing has been observed by wide-angle X-ray diffraction. From the systematic
      study of the temperature dependence of simultaneous small- and wide-angle X-ray
      diffraction patterns, we demonstrate that the intercellular lipid matrix forms
      two domains, which consist at room temperature of a long lamellar structure with
      hexagonal hydrocarbon-chain packing and a short lamellar structure with
      orthorhombic hydrocarbon-chain packing.

PMID- 17034757
TI  - Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of
      alpha-dystroglycan.
AB  - The recent identification of mutations in genes encoding demonstrated or putative
      glycosyltransferases has revealed a novel mechanism for congenital muscular
      dystrophy. Hypoglycosylated alpha-dystroglycan (alpha-DG) is commonly seen in
      Fukuyama-type congenital muscular dystrophy (FCMD), muscle-eye-brain disease
      (MEB), Walker-Warburg syndrome (WWS), and Large(myd) mice. POMGnT1 and POMTs, the
      gene products responsible for MEB and WWS, respectively, synthesize unique O
      mannose sugar chains on alpha-DG. The function of fukutin, the gene product
      responsible for FCMD, remains undetermined. Here we show that fukutin co
      localizes with POMGnT1 in the Golgi apparatus. Direct interaction between fukutin
      and POMGnT1 was confirmed by co-immunoprecipitation and two-hybrid analyses. The
      transmembrane region of fukutin mediates its localization to the Golgi and
      participates in the interaction with POMGnT1. Y371C, a missense mutation found in
      FCMD, retains fukutin in the ER and also redirects POMGnT1 to the ER. Finally, we
      demonstrate reduced POMGnT1 enzymatic activity in transgenic knock-in mice
      carrying the retrotransposal insertion in the fukutin gene, the prevalent
      mutation in FCMD. From these findings, we propose that fukutin forms a complex
      with POMGnT1 and may modulate its enzymatic activity.

PMID- 17034758
TI  - A novel phytase with preferable characteristics from Yersinia intermedia.
AB  - A Yersinia intermedia strain producing phytase was isolated from glacier soil.
      The phytase gene, appA, was isolated by degenerate PCR and TAIL-PCR. The full
      length fragment contained 2354bp with a 1326-bp open reading frame encoding 441
      amino acids. APPA contained the active site RHGXRXP and HD sequence motifs that
      are typical of histidine acid phosphatases. To our knowledge, this is the first
      report of the detection of phytase activity and cloning of the relevant gene from
      Y. intermedia. The gene was overexpressed in Pichia pastoris, and the purified
      recombinant APPA had a specific activity for sodium phytate of 3960U/mg, which is
      higher than that of the Citrobacter braakii phytase (previously the highest
      specific activity known). Recombinant APPA had high activity from pH 2 to 6
      (optimum 4.5) and optimal temperature of 55 degrees C; the enzyme was resistant
      to pepsin and trypsin. These characteristics suggest that APPA may be highly
      suitable for use in the feed industry.

PMID- 17034759
TI  - Oxidative stress-induced intestinal epithelial cell apoptosis is mediated by p38
      MAPK.
AB  - Free oxygen radicals are involved in the pathogenesis of necrotizing
      enterocolitis (NEC) in premature infants. The stress-activated p38 mitogen
      activated protein kinase (MAPK) has been implicated in gut injury. Here, we found
      that phosphorylated p38 was detected primarily in the villus tips of normal
      intestine, whereas it was expressed in the entire mucosa in NEC. H(2)O(2)
      treatment resulted in a rapid phosphorylation of p38 MAPK and subsequent
      apoptosis of rat intestinal epithelial (RIE)-1 cells; this induction was
      attenuated by treatment with SB203580, a selective p38 MAPK inhibitor, or
      transfection with p38alpha siRNA. Moreover, SB203580 also blocked H(2)O(2)
      induced PKC activation. In contrast, the PKC inhibitor (GF109203x) did not affect
      p38 activation, indicating that p38 MAPK activation occurs upstream of PKC
      activation in H(2)O(2)-induced apoptosis. H(2)O(2) treatment also decreased
      mitochondrial membrane potential; pretreatment with SB203580 attenuated this
      response. Our study demonstrates that the p38 MAPK/PKC pathway plays an important
      role as a pro-apoptotic cellular signaling during oxidative stress-induced
      intestinal epithelial cell injury.

PMID- 17034760
TI  - A threonine synthase homolog from a mammalian genome.
AB  - The genomes of several vertebrates contain two genes encoding proteins highly
      similar to threonine synthase (TS), even though the biosynthesis of l-threonine
      (l-Thr) is not known to occur in these animals. We report a bioinformatic
      analysis of the two TS-like genes, the recombinant expression of one murine TS
      homolog (mTSH2) and its initial biochemical characterization. Recombinant mTSH2
      contained bound pyridoxal-5'-phosphate (PLP), but did not synthesize l-Thr. The
      enzyme did, however, bind O-phospho-homoserine (PHS; the actual TS substrate) and
      degraded it to alpha-ketobutyrate, phosphate, and ammonia-a known side reaction
      of microbial TSs. mTSH2 also degraded O-phospho-threonine (PThr) to alpha
      ketobutyrate, showing that it can act as a catabolic phospho-lyase on both gamma-
      and beta-phosphorylated substrates. These findings suggest an unusual
      evolutionary origin for mTSH2, whereby an original TS enzyme became 'recycled'
      into a phospho-lyase upon dismissal, in metazoa, of the l-Thr biosynthetic
      pathway.

PMID- 17034762
TI  - Amiloride attenuates glycine-induced currents in cultured neurons of rat inferior
      colliculus.
AB  - Amiloride, a potassium sparing diuretic, is well known to interact with many ion
      transport systems and modulate the activity of several membrane receptors.
      However, relatively little information is available as to how amiloride affects
      membrane receptors of neurons in the brain areas. In the present study, we
      investigated the effects of amiloride on glycine-induced currents (I(Gly)) in
      cultured neurons of rat inferior colliculus with whole-cell patch-clamp
      recordings. Amiloride itself did not activate any current across the neuronal
      membrane but it reversibly inhibited the amplitude of the I(Gly) in a reversible
      and concentration-dependent manner, with an IC(50) of 487.4+/-25.3microM (n=5).
      Amiloride shifted the concentration-response relationship to the right without
      changing Hill coefficient and without changing the maximum response of the
      I(Gly). The pre-perfusion of amiloride produced an inhibitory effect on the
      I(Gly). In addition, amiloride was shown with a voltage ramp protocol to
      significantly reduce the conductance induced by glycine but not to change the
      reversal potential of the I(Gly). These results demonstrate that amiloride
      competitively inhibits the I(Gly) in rat inferior colliculus neurons by
      decreasing the affinity of glycine to its receptor. Our finding suggests that
      attention should be paid to the possible side effects of amiloride used as a drug
      on brain functions in the case of a defective blood-brain barrier and in the case
      of direct application of this drug into the cerebrospinal fluid for treatment of
      brain tumors.

PMID- 17034761
TI  - Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced
      homodimerization of TLR4.
AB  - Toll-like receptors (TLRs), which are activated by invading microorganisms or
      endogenous molecules, evoke immune and inflammatory responses. TLR activation is
      closely linked to the development of many chronic inflammatory diseases including
      rheumatoid arthritis. Auranofin, an Au(I) compound, is a well-known and long-used
      anti-rheumatic drug. However, the mechanism as to how auranofin relieves the
      symptom of rheumatoid arthritis has not been fully clarified. Our results
      demonstrated that auranofin suppressed TLR4-mediated activation of transcription
      factors, NF-kappaB and IRF3, and expression of COX-2, a pro-inflammatory enzyme.
      This suppression was well correlated with the inhibitory effect of auranofin on
      the homodimerization of TLR4 induced by an agonist. Furthermore, auranofin
      inhibited NF-kappaB activation induced by MyD88-dependent downstream signaling
      components of TLR4, MyD88, IKKbeta, and p65. IRF3 activation induced by MyD88
      independent signaling components, TRIF and TBK1, was also downregulated by
      auranofin. Our results first demonstrate that auranofin suppresses the multiple
      steps in TLR4 signaling, especially the homodimerization of TLR4. The results
      suggest that the suppression of TLR4 activity by auranofin may be the molecular
      mechanism through which auranofin exerts anti-rheumatic activity.

PMID- 17034763
TI  - Transcriptional targeting of small interfering RNAs into cancer cells.
AB  - Small interfering RNAs (siRNAs) are widely used for analyzing gene function and
      have the potential to be developed into human therapeutics. However, persistent
      siRNA expression in normal cells may cause toxic side effects. Therefore, the
      therapeutic applications of RNAi in cancer require either the specific delivery
      of synthetic siRNAs into cancer cells or the control of siRNA expression.
      Accordingly, we have developed a cancer-specific vector that expresses siRNAs
      from the human survivin promoter. A plasmid vector expressing siRNAs under this
      promoter enabled efficient gene silencing of gene expression in different cancer
      cell lines. The levels of inhibition were comparable to that obtained with the
      constitutively active U6 promoter. By contrast to U6 promoter, no significant
      gene silencing was obtained with the Survivin promoter in normal mammary
      epithelial cells. Collectively, these data indicate that the survivin promoter is
      suitable for directing siRNA expression in cancer cells, but not normal cells.

PMID- 17034764
TI  - Identification of two biologically crucial hydroxyl groups of (-)
      epigallocatechin gallate in osteoclast culture.
AB  - (-)-Epigallocatechin gallate (EGCG) induces cell death of osteoclasts in an
      Fe(2+)- and H(2)O(2)-dependent manner. In the present study, we further explore
      the cytotoxic mechanism of EGCG using four EGCG analogues. Molecules methylated
      at position 4' in the B ring (EGCG-4'-O-Me) or at position 4'' in the D-ring
      (EGCG-4''-O-Me) showed markedly decreased cytotoxicity to osteoclasts, indicating
      that hydroxyl groups at these two positions of EGCG are crucial for inducing cell
      death of osteoclasts. EGCG-4'-O-Me also showed the lowest Fe(3+)-reducing
      activity among five EGCGs. The Fe(3+)-reducing activity of EGCG was enhanced
      under conditions whereby protonated EGCG levels were increased, indicating that
      the protonated status of EGCG was involved in the Fe(3+)-reducing activity. The
      hydroxyl group at position 4'' in the D-ring was shown by quantum chemical
      calculation to be preferentially deprotonated among all of the hydroxyl groups in
      EGCGs. It was also shown that the highest occupied molecular orbital (HOMO) was
      localized to the B-ring of EGCGs, except for EGCG-4'-O-Me. We report here that
      the HOMO on the B-ring plays crucial roles in both the Fe(3+)-reducing activity
      of EGCG and the cytotoxicity of EGCG to osteoclasts, while deprotonation of the
      hydroxyl group at position 4'' in the D-ring plays a supplementary role.

PMID- 17034765
TI  - "Non-serotonergic" lateral superior olivary neurons of the neonatal mouse contain
      serotonin.
AB  - In mutant mice which have high serotonin (5-HT) levels perinatally, neurons in
      the lateral superior olive (LSO, which are not serotonergic), contain 5-HT
      transiently in the neonatal period of development. We determined that the same
      phenomenon occurs in non-genetically altered mice: LSO neurons were 5-HT
      immunoreactive at postnatal days 1 and 8. These findings suggest accumulation of
      5-HT in by LSO neurons during postnatal development.

PMID- 17034767
TI  - Effect of gravity on human spontaneous 10-Hz electroencephalographic oscillations
      during the arrest reaction.
AB  - Electroencephalographic oscillations at 10 Hz (alpha and mu rhythms) are the most
      prominent rhythms observed in awake, relaxed (eye-closed) subjects. These
      oscillations may be considered as a marker of cortical inactivity or an index of
      the active inhibition of the sensory information. Different cortical sources may
      participate in the 10-Hz oscillation and appear to be modulated by the sensory
      context and functional demands. In microgravity, the marked reduction in
      multimodal graviceptive inputs to cortical networks participating in the
      representation of space could be expected to affect the 10-Hz activity. The
      effect of microgravity on this basic oscillation has heretofore not been studied
      quantitatively. Because the alpha rhythm has a functional role in the regulation
      of network properties of the visual areas, we hypothesised that the absence of
      gravity would affect its strength. Here, we report the results of an experiment
      conducted over the course of 3 space flights, in which we quantified the power of
      the 10-Hz activity in relation to the arrest reaction (i.e., in 2 distinct
      physiological states: eyes open and eyes closed). We observed that the power of
      the spontaneous 10-Hz oscillation recorded in the eyes-closed state in the
      parieto-occipital (alpha rhythm) and sensorimotor areas (mu rhythm) increased in
      the absence of gravity. The suppression coefficient during the arrest reaction
      and the related spectral perturbations produced by eye-opening/closure state
      transition also increased in on orbit. These results are discussed in terms of
      current theories on the source and the importance of the alpha rhythm for
      cognitive function.

PMID- 17034766
TI  - Proteomic analysis of the effects of cocaine on the enhancement of HIV-1
      replication in normal human astrocytes (NHA).
AB  - The US is experiencing an epidemic of cocaine use entangled with HIV-1 infection.
      Normal human astrocytes (NHA) are susceptible to HIV-1 infection. We utilized LTR
      R/U5 amplification, p24 antigen assay and the proteomic method of difference gel
      electrophoresis (DIGE) combined with protein identification through HPLC-MS/MS to
      investigate the effect of cocaine on HIV-1 infectivity and the proteomic profile
      of NHA, respectively. Data demonstrate that cocaine significantly upregulates HIV
      1 infection in NHA as measured by LTR-R/U5 amplification and p24 antigen assay.
      Further, our results show for the first time that cocaine differentially
      regulates the expression of a number of proteins by NHA that may play a role in
      the neuropathogenesis of HIV-1 disease.

PMID- 17034768
TI  - An ERP investigation of emotional processing in European and Japanese
      individuals.
AB  - This article examined neural time course differences in the processing of
      emotional pictures in European and Asian individuals. Event-related potentials
      (ERPs) were recorded in 15 French and 15 Japanese volunteers during the
      presentation of neutral and emotional pictures in their own country. ERPs were
      analyzed by means of spatio-temporal Principal Component Analysis (PCA) and allow
      to evaluate cultural influences on emotional processing along three temporal
      windows: 105 to 140 ms, 176 to 230 ms and 255 to 455 ms. Main results highlight
      that (1) early ERP components coded emotional charge but were not modulated by
      cultural background, (2) later components showed a significant decrease of
      amplitudes at parieto-occipital areas for Japanese participants compared to
      French ones in emotional condition. These findings suggest that, in both
      populations, similar neurocognitive processes are involved in the early stage of
      the emotional stimuli processing and effects observed on later components may
      reflect a poorer engagement of parietal areas, known to be involved in emotional
      arousal dimension. Considering that cognitive judgments were similar in both
      populations, electrophysiological findings suggest that cultural influences on
      later stage of emotional processing could be related to the known lower level of
      emotionally expressive behavior in Japanese than in Caucasians.

PMID- 17034769
TI  - PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes.
AB  - 5-aminolevulinic acid (ALA) and carnosine have important physiological and
      pathophysiological roles in the CNS. Both are substrates for the proton-coupled
      oligopeptide transporter PEPT2. The purpose of the current study was to determine
      the importance of PEPT2 in the uptake of ALA and carnosine in rat and mouse
      (PEPT2+/+ and PEPT2-/-) cultured neonatal astrocytes. Although neonatal
      astrocytes are known to express PEPT2, its quantitative importance in the
      transport of these compounds is not known. [14C]ALA uptake in neonatal rat
      astrocytes was inhibited by dipeptides, an alpha-amino containing cephalosporin
      (which is a PEPT2 substrate) but was not affected by a non-amino containing
      cephalosporin (which is not a PEPT2 substrate). Uptake was pH sensitive as
      expected from a proton-coupled transporter and was saturable (Vmax=715+/-29
      pmol/mg/min, Km=606+/-14 microM). [3H]Carnosine uptake in neonatal rat astrocytes
      was inhibited by dipeptides but not by histidine (a substrate for the
      peptide/histidine transporters PHT1 and PHT2) and also showed saturable transport
      (Vmax=447+/-23 pmol/mg/min, Km=43+/-5.5 microM). Neonatal astrocytes from PEPT2-/
      mice had a 62% reduction in [14C]ALA uptake and a 92% reduction in [3H]carnosine
      uptake compared to PEPT2+/+ mice. These results demonstrate that PEPT2 is the
      primary transporter responsible for the astrocytic uptake of ALA and carnosine.

PMID- 17034770
TI  - Cyclomaltooligosaccharide-assisted spectroscopic discrimination of phthalimido
      derived amino acids through the formation of molecular aggregates.
AB  - Spectroscopic evidence was used to demonstrate the formation of molecular
      associates in an aqueous solution of phthalimido tryptophan. These molecular
      associates are loosely formed through pi-pi aromatic stacking, properties that
      are not sufficient to cause NMR spectroscopic enantiomeric discrimination. A
      cyclomaltooligosaccharide with a larger cavity, such as cyclomaltooctaose (gamma
      cyclodextrin), is capable of forming a ternary complex with these molecular
      associates and enhances pi-pi aromatic stacking interactions, resulting in NMR
      enantiomeric discrimination. Electrospray-ionization mass spectroscopy (ESIMS)
      and NOESY two-dimensional NMR spectroscopic methods were used to study these
      complexes. Association constants and thermodynamic data for these
      cyclomaltooligosaccharide complexes were also estimated.

PMID- 17034771
TI  - Fatty acid transporter levels and palmitate oxidation rate correlate with
      ejection fraction in the infarcted rat heart.
AB  - OBJECTIVES: Cardiac fatty acid uptake occurs predominantly via sarcolemmal
      transporter proteins; fatty acid translocase (FAT/CD36), plasma membrane fatty
      acid binding protein (FABPpm) and fatty acid transporter proteins (FATP) 1 and 6.
      We hypothesised that levels of the fatty acid transporters would be reduced in
      the chronically infarcted rat heart, in parallel with reduced dependence on fatty
      acid utilisation. METHODS AND RESULTS: In vivo left ventricular ejection
      fractions, measured using echocardiography, were 36% lower in rats six months
      after coronary artery ligation than in sham-operated control rats. In isolated,
      perfused, infarcted hearts, 3H-palmitate oxidation was 30% lower, and correlated
      with in vivo ejection fractions. As myocardial lipid incorporation was also
      reduced by 25%, total palmitate utilisation was 29% lower in the infarcted rat
      heart. The protein levels of the cardiac fatty acid transporters were reduced in
      the infarcted rat heart; FAT/CD36 by 36%, FABPpm by 12%, FATP6 by 21% and FATP1
      by 26%, and the cytosolic fatty acid binding protein (cFABP) was 47% lower than
      in sham-operated rat hearts. Fatty acid transporter levels correlated with both
      palmitate oxidation rates and cardiac ejection fractions. CONCLUSIONS: Reductions
      in fatty acid oxidation and lipid incorporation rates were accompanied by
      downregulation of the cardiac fatty acid transporters. The metabolic shift away
      from fatty acid utilisation was proportional to the degree of functional
      impairment in the chronically infarcted rat heart.

PMID- 17034772
TI  - Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic
      heart failure.
AB  - Chronic heart failure is a complex catabolic state that carries a devastating
      prognosis. The transition from stable disease to cardiac cachexia is not well
      understood. Mechanisms that maintain the wasting process involve neurohormones
      and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and
      catabolic pathways. A decrease in food intake alone rarely triggers the
      development of a wasting process, but dietary deficiencies in micronutrients and
      macronutrients contribute to the progression of the disease. Malabsorption from
      the gut as a result of bowel wall edema and decreased bowel perfusion also plays
      an important role. This article describes the complex interplay of hormonal
      systems in energy balance in patients with chronic heart failure as well as other
      factors such as malabsorption and dietary deficiencies that contribute to the
      wasting process. Finally, therapeutic approaches are discussed. These include
      dietary advice, ongoing studies, and future possibilities.

PMID- 17034773
TI  - Phosphodiesterase 7A1 is expressed in human CD4+ naive T cells at higher levels
      than in CD4+ memory cells and is not required during their CD3/CD28-dependent
      activation.
AB  - PDE7A1 is a cAMP-hydrolyzing phosphodiesterase expressed in lymphoid tissue,
      where its possible role during T cell activation remains unclear. We have
      characterized the functional relevance of PDE7A1 in the naive (CD4+CD45RA+) and
      memory (CD4+CD45RO+) subsets of human peripheral CD4+ T cells during CD3/CD28
      dependent stimulation. Our results indicate that PDE7A1 is expressed in resting
      naive CD4+ T cells at higher levels than in the corresponding memory cells and
      that levels of PDE7A1 mRNA are not upregulated upon CD3/CD28 mediated stimulation
      of these T cell subsets. Treatment with a selective inhibitor of PDE7A1 does not
      impair CD3/CD28 induced activation of naive or memory CD4+ T cells, nor does it
      increase intracellular cAMP in CD4+ T cells. We conclude that PDE7A1 is not
      required during CD3/CD28-dependent activation of naive and memory CD4+ T cells,
      but cannot rule out other regulatory roles of PDE7A1 during maturation of CD4+ T
      cells.

PMID- 17034774
TI  - Lactoferrin activates macrophages via TLR4-dependent and -independent signaling
      pathways.
AB  - Lactoferrin (LF) is a component of innate immunity and is known to interact with
      accessory molecules involved in the TLR4 pathway, including CD14 and LPS binding
      protein, suggesting that LF may activate components of the TLR4 pathway. In the
      present study, we have asked whether bovine LF (bLF)-induced macrophage
      activation is TLR4-dependent. Both bLF and LPS stimulated IL-6 production and
      CD40 expression in RAW 264.7 macrophages and in BALB/cJ peritoneal exudate
      macrophages. However, in macrophages from congenic TLR4(-/-) C.C3-Tlr4(lps-d)
      mice, CD40 was not expressed while IL-6 secretion was increased relative to wild
      type cells. The signaling components NF-kappaB, p38, ERK and JNK were activated
      in RAW 264.7 cells and BALB/cJ macrophages after bLF or LPS stimulation,
      demonstrating that the TLR4-dependent bLF activation pathway utilizes signaling
      components common to LPS activation. In TLR4 deficient macrophages, bLF-induced
      activation of NF-kappaB, p38, ERK and JNK whereas LPS-induced cell signaling was
      absent. We conclude from these studies that bLF induces limited and defined
      macrophage activation and cell signaling events via TLR4-dependent and 
      independent mechanisms. bLF-induced CD40 expression was TLR4-dependent whereas
      bLF-induced IL-6 secretion was TLR4-independent, indicating potentially separate
      pathways for bLF mediated macrophage activation events in innate immunity.

PMID- 17034775
TI  - Antiangiogenic effect of Lygodium flexuosum against N-nitrosodiethylamine-induced
      hepatotoxicity in rats.
AB  - The antiangiogenic effect of Lygodium flexuosum extract was evaluated in Wistar
      rats intoxicated with N-nitrosodiethylamine (NDEA) in preventive and curative
      models. In preventive groups, NDEA was administered for 20 weeks. Daily doses of
      L. flexuosumn-hexane extract (200mg/kg) started 1 week before the onset of NDEA
      intoxication and continued for 20 weeks. In curative animals, NDEA was
      administered for 20 weeks followed by treatment with the n-hexane extract of L.
      flexuosum for 28 days. Rats intoxicated with NDEA had elevated levels of serum
      gamma-GT, AST, ALT, LDH levels and hepatic MDA and decreased levels of hepatic
      GSH. When treated with L. flexuosum extract had normal levels of gamma-GT, AST,
      ALT, LDH levels, hepatic MDA and GSH. NDEA administered rat liver showed an
      overexpressed levels of angiopoietins 1 (Ang-1) and 2 (Ang-2) and its receptor
      Tie-2 mRNA. L. flexuosum extract treatment significantly (p<or=0.05) reduced the
      levels of Ang-1 and Ang-2 and Tie-2 in rat livers evidenced by RT-PCR.
      Immunohistochemical analysis showed that vascular endothelial growth factor
      (VEGF) was overexpressed and localized around periportal area of liver sections
      intoxicated with NDEA and its overexpression was effectively reduced by the
      treatment with L. flexuosum extract. Histopathological observations also
      substantiated NDEA-induced hepatotoxicity and the effect was significantly
      (p<or=0.05) reduced by L. flexuosum extract treatment. Thus, L. flexuosum extract
      at a dose of 200mg/kg effectively reversed the hepatotoxicity induced by N
      nitrosodiethylamine in both experimental models.

PMID- 17034776
TI  - Suggested functions for prolyl oligopeptidase: a puzzling paradox.
AB  - Prolyl oligopeptidase (PO, E.C. 3.4.21.26) is a post-proline cleaving enzyme with
      endopeptidase activity towards peptides not longer than 30 amino acids. It has
      been purified and characterized from various mammalian and bacterial sources, but
      despite its thorough enzymological and structural characterization, the exact
      function of PO remains obscure. Many investigations have addressed the
      physiological role of this enzyme, mainly by the use of specific PO inhibitors,
      activity measurements in clinical samples and (neuro)peptide degradation studies.
      From the combined results emerges a puzzling paradox: how can an intracellular,
      cytoplasmatic oligopeptidase affect not only the amount of extracellular
      neuropeptides but also signal transduction and secretion? This report provides a
      review of the literature on the suggested functions for PO, highlighting possible
      pitfalls and contradictions.

PMID- 17034777
TI  - DNA-based diagnosis of mucolipidosis type IIIA and mucopolysacchariodisis type VI
      in a Chinese family: a chance of 1 in 7.6 trillion.

PMID- 17034778
TI  - Comparison between two commercially available chromogranin A assays in detecting
      neuroendocrine differentiation in prostate cancer and benign prostate
      hyperplasia.
AB  - BACKGROUND: Chromogranin A (CgA) is the neuroendocrine (NE) marker most
      frequently employed in detecting NE differentiation in prostate cancer patients,
      either at the tissue level or in the general circulation. METHODS: We compared
      the two commercially CgA assay kits in detecting NE differentiation, in benign
      hyperplasia (BPH) or prostate cancer (PC) patients (pts). 170 pts with BPH, 107
      with BPH+inflammation, and 136 PC pts entered the study. CgA was measured in each
      patient with the immunoradiometric assay (IRMA) and with the enzyme-linked
      immunoabsorbent assay (ELISA). RESULTS: A moderate relationship was found between
      CgA measured with IRMA and ELISA in the whole population (Spearman's R=0.65,
      p<0.05), in BPH pts (R=0.76, p<0.05), in BPH+inflammation pts (R=0.53, p<0.05)
      and in PC pts (R=0.60, p<0.05). Twenty-two out of 62 pts (35.4%) with elevated
      ELISA CgA did not have increased IRMA CgA; by contrast, 21/61 pts (34.4%) with
      elevated IRMA CgA were not recognized as abnormal by the ELISA kit. CONCLUSIONS:
      CgA measured by the two assays provided a significant discordance rate,
      suggesting that the two kits might elicit different information.

PMID- 17034779
TI  - Adaptive control: a review of the ability to acquire and maintain high
      sensorimotor performance.
AB  - When the relationship which relates us to the environment through vision, often
      named visual mapping, is durably modified, our behaviour is altered at sensory,
      motor and cognitive levels. The brain has the ability through the so-called
      adaptive control to progressively decrease the motor errors despite visual image
      alteration. Adaptive control in both the visuo-manual and the vestibulo-ocular
      systems is reviewed. A parallel is tentatively made between adaptation to
      ordinary optical alterations (resulting from the use of refraction-corrective
      glasses) in the visual mapping of these two systems and the adaptation to more
      complex visuo-motor relationships experienced by people working in virtual
      environments.

PMID- 17034780
TI  - Optimal selection of wavelet-packet-based features using genetic algorithm in
      pathological assessment of patients' speech signal with unilateral vocal fold
      paralysis.
AB  - Unilateral vocal fold paralysis (UVFP) is one of the most severe types of
      neurogenic laryngeal disorder in which the patients, due to their vocal cords
      malfunction, are confronted by some serious problems. As the effect of such
      pathologies would be significantly evident in the reduced quality and feature
      variation of dysphonic voices, this study is designed to scrutinize the piecewise
      variation of some specific types of these features, known as energy and entropy,
      all over the frequency range of pathological speech signals. In order to do so,
      the wavelet-packet coefficients, in five consecutive levels of decomposition, are
      used to extract the energy and entropy measures at different spectral sub-bands.
      As the decomposition procedure leads to a set of high-dimensional feature
      vectors, genetic algorithm is invoked to search for a group of optimal sub-band
      indexes for which the extracted features result in the highest recognition rate
      for pathological and normal subjects' classification. The results of our
      simulations, using support vector machine classifier, show that the highest
      recognition rate, for both optimized energy and entropy measures, is achieved at
      the fifth level of wavelet-packet decomposition. It is also found that entropy
      feature, with the highest recognition rate of 100% vs. 93.62% for energy, is more
      prominent in discriminating patients with UVFP from normal subjects. Therefore,
      entropy feature, in comparison with energy, demonstrates a more efficient
      description of such pathological voices and provides us a valuable tool for
      clinical diagnosis of unilateral laryngeal paralysis.

PMID- 17034781
TI  - Ocular surface temperature: a 3D FEM prediction using bioheat equation.
AB  - Computational and mathematical human eye models from previous studies which were
      constructed in two-dimensions (2D) did not give a precise representation of the
      actual human eye. This work is an extension from an earlier published work on the
      2D model. In this paper, a 3D FEM model of the human eye is simulated for the
      steady state temperature distribution during normal condition and during
      electromagnetic (EM) wave radiation. Results show a discrepancy of 0.49% for a
      normal condition as opposed to 1.9% of a 2D model when compared to experimental
      results from open literatures. Investigations on the EM wave radiations found an
      average power absorption density of 15,151 and 22,145 Wm(-3) for the 750 and 1500
      MHz radiation, respectively. A peak temperature of 38.18( composite function)C
      was predicted for the 750 MHz radiation while 41.19( composite function)C was
      computed for the 1500 MHz radiation. These temperatures are in reasonable
      agreement with the simulated results computed by another report in the past.

PMID- 17034782
TI  - The presumptive floor plate (notoplate) induces behaviors associated with
      convergent extension in medial but not lateral neural plate cells of Xenopus.
AB  - In previous work (Elul, T., Keller, R., 2000. Monopolar protrusive activity: a
      new morphogenic cell behavior in the neural plate dependent on vertical
      interactions with the mesoderm in Xenopus. Dev. Biol. 224, 3-19; Ezin, A.M.,
      Skoglund, P. Keller, R. 2003. The midline (notochord and notoplate) patterns the
      cell motility underlying convergence and extension of the Xenopus neural plate.
      Dev. Biol. 256, 100-114), the midline tissues of notochord and overlying
      notoplate were found to induce the monopolar, medially directed protrusive
      activity of deep neural cells. This behavior is thought to drive the mediolateral
      intercalation and convergent extension of the neural plate in Xenopus. Here we
      address the issue of whether the notochord, the notoplate, or both is essential
      for this induction. Our strategy was to remove the notochord, leaving the
      overlying notoplate intact, and determine whether it alone can induce the
      monopolar, medially directed cell behavior. We first establish that the notoplate
      (presumptive floor plate), when separated from the underlying notochord in the
      early neurula (stages 13-14), will independently mature into a floor plate as
      assayed three criteria: (1) continued expression of an early marker, sonic
      hedgehog, and a later, marker, F-spondin; (2) the display of the notoplate/floor
      plate-specific randomly oriented protrusive activity; (3) the characteristic lack
      of mixing of cells between the notoplate and lateral neural plate. Under these
      conditions, in the presence of a mature notoplate/floor plate and in the absence
      of the notochord, the characteristic monopolar, medially directed behavior
      occurred, but only locally near the midline. These results show that the
      notoplate/floor plate capacity to induce the medially directed motility is
      limited in range, and they suggest that the notochord is necessary for the
      normally observed longer range induction in lateral neural plate cells. This work
      helps to further the understanding of molecular and tissue interactions required
      for convergent extension.

PMID- 17034783
TI  - Specialized extraembryonic cells connect embryonic and extraembryonic epidermis
      in response to Dpp during dorsal closure in Drosophila.
AB  - Dorsal closure in Drosophila embryogenesis involves expansion of the dorsal
      epidermis, followed by closure of the opposite epidermal edges. This process is
      driven by contractile force generated by an extraembryonic epithelium covering
      the yolk syncytium known as the amnioserosa. The secreted signaling molecule Dpp
      is expressed in the leading edge of the dorsal epidermis and is essential for
      dorsal closure. We found that the outermost row of amnioserosa cells (termed pAS)
      maintains a tight basolateral cell-cell adhesion interface with the leading edge
      of dorsal epidermis throughout the dorsal closure process. pAS was subject to
      altered cell motility in response to Dpp emanating from the dorsal epidermis, and
      this response was essential for dorsal closure. alphaPS3 and betaPS integrin
      subunits accumulated in the interface between pAS and dorsal epidermis, and were
      both required for dorsal closure. Looking at alphaPS3, type I Dpp receptor, and
      JNK mutants, we found that pAS cell motility was altered and pAS and dorsal
      epidermis adhesion failed under the mechanical stress of dorsal closure,
      suggesting that a Dpp-mediated mechanism connects the squamous pAS to the
      columnar dorsal epidermis to form a single coherent epithelial layer.

PMID- 17034784
TI  - Oxidative DNA damage estimated by urinary 8-hydroxydeoxyguanosine and indoor air
      pollution among non-smoking office employees.
AB  - This study investigated whether urinary 8-hydroxydeoxyguanosine (8-OHdG), a
      biomarker of oxidative stress, was associated with indoor air quality for non
      smokers in high-rise building offices. With informed consents, urine samples from
      344 non-smoking employees in 86 offices were collected to determine 8-OHdG
      concentrations. The concentrations of carbon dioxide (CO(2)) and total volatile
      organic compounds (TVOCs) in each office and outside of the building were
      simultaneously measured for eight office hours. The average workday difference
      between indoor and outdoor CO(2) concentrations (dCO(2)) was used as a surrogate
      measure of the ventilation efficiency for each office unit. The CO(2) levels in
      the offices ranged 467-2810ppm with a mean of 1170ppm, or 2.7 times higher than
      that in the outside air. The average urinary 8-OHdG levels among employees
      increased from 3.10 micro g/g creatinine, for those at the lowest tertile levels
      of both dCO(2) and TVOCs, to 6.27 micro g/g creatinine, for those at the highest
      tertile levels. Multivariate logistic regression analysis showed that the risk of
      having the urinary 8-OHdG level of greater than the median, 4.53 micro g/g
      creatinine, for participants was increased significantly at the highest tertile
      dCO(2) level of >680ppm (odds ratio (OR)=3.37, 95% confidence interval (CI)=1.20
      9.46). The effect was significant at the middle tertile TVOCs level of 114-360ppb
      (OR=2.62, 95% CI=1.43-4.79), but not at the highest tertile. Inadequate
      ventilation in office increases the risk of building-related oxidative stress in
      non-smoking employees.

PMID- 17034785
TI  - Absorption of folate by Caco-2 cells is not affected by high glucose
      concentration.
AB  - The aim of this work was to investigate the effect of high glucose exposure on
      the absorption of folate by Caco-2 cells. We verified that apical high glucose
      did not affect the apical uptake of [(3)H]folate. Both different concentrations
      of glucose (10-45 mM) and different exposure times (10 min-24 h) were tested.
      Furthermore, apical high glucose (30 mM) did not affect the intracellular steady
      state levels of [(3)H]folate, and simultaneous apical and basolateral high
      glucose (30 mM) did not change the apical-to-basolateral apparent permeability
      (P(app)) to [(3)H]folate. Both the apical uptake and the steady-state
      intracellular levels of [(3)H]folate were strongly reduced by 5
      methyltetrahydrofolate, methotrexate, SITS (4-acetamido-4'-isothiocyanato-2,2'
      stilbenedisulfonic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid) and indomethacin, but were not affected or only hardly affected by p
      aminohippuric acid and fumitremorgin C. Moreover, DIDS and indomethacin
      significantly reduced (by 50-60%) the apical-to-basolateral P(app) to
      [(3)H]folate, but [(3)H]folate present in the cells at the end of the experiment
      was higher in the case of indomethacin. Fumitremorgin C had no effect. The effect
      of the drugs tested was not changed or only hardly changed by high glucose. In
      conclusion, absorption of [(3)H]folate is not modulated by either apical or
      basolateral high glucose exposure in Caco-2 cells. Moreover, our results suggest
      that the apical uptake of [(3)H]folate by Caco-2 cells involves the Reduced
      Folate Transporter (but not the Organic Anion Transporter), and that Multidrug
      Resistance Protein and/or Organic Anion Transporter (but not Breast Cancer
      Resistance Protein) may mediate apical efflux of [(3)H]folate.

PMID- 17034786
TI  - Baclofen and potential therapeutic use: studies of neuronal survival.
AB  - Up to now, baclofen (a GABA(B) receptor agonist) has been used for the treatment
      of severe spasticity unresponsive to oral antispasmodics. Although in humans it
      is usually administered at 2 mg/ml, the dosage to be used in the treatment of
      other diseases is unknown. For this reason, it is important to determine the safe
      maximum dosage and toxicity at the clinically used concentration. Primary
      cortical neurons represent a useful model to test the safety of baclofen. We
      performed a colorimetric assay (MTT test) as well as electron microscopy
      investigations, to determine neuronal survival after the treatment with baclofen
      at a concentration of 2 and 4 mg/ml. Our results demonstrated that, in our
      experimental model, neither concentration affected neuronal survival. Considering
      the above results, we can conclude that at the used concentrations, this drug is
      safe and its clinical use should be encouraged.

PMID- 17034787
TI  - The selective effect of cystathionine on doxorubicin hepatotoxicity in tumor
      bearing mice.
AB  - The aim of the present study was to examine the protective effect of
      cystathionine as a cysteine precursor on doxorubicin toxicity in the liver of
      Ehrlich ascites tumor (EAT)-bearing mice and in the EAT cells. Both compounds
      were injected intraperitoneally alone or in combination at the following doses:
      cystathionine at 10 mg and doxorubicin at 5 mg per kg of body weight. In the
      liver of EAT-bearing mice, glutathione (GSH), cysteine and sulfane sulfur levels
      as well as the activities of: glutathione S-transferase, gamma-glutamyl
      transpeptidase, rhodanese and gamma-cystathionase significantly dropped in
      comparison with healthy animals. Administration of cystathionine elevated GSH and
      cysteine levels in the livers of EAT-bearing mice and reduced lipid peroxidation.
      Furthermore, cystathionine increased gamma-glutamyl transpeptidase activity,
      thereby activating gamma-glutamyl cycle, responsible for proper glutathione
      metabolism in the cells. Cystationine did not influence sulfane sulfur level and
      rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice. It
      was next shown that cystathionine administered in combination with doxorubicin
      protected against the drug toxicity since it elevated thiol level, lowering
      reactive oxygen species content and suppressing lipid peroxidation. This means
      that, cystathionine in the liver of EAT-bearing mice can both correct harmful
      effects of carcinogenesis, and protect the liver from doxorubicin cytotoxicity.
      In contrast, in EAT cells, cystathionine lowered GSH and cysteine levels and did
      not alter reactive oxygen species level, lipid peroxidation, and gamma-glutamyl
      transpeptidase activity. All these data indicate that cystathionine action is
      selectively beneficial for normal cells because it corrects harmful effects
      induced by EAT development and protects the organism against doxorubicin
      cytotoxicity without impairing cytotoxicity of this drug to tumor cells.

PMID- 17034788
TI  - CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and
      cytokeratin aggresome (Mallory body-like) formation.
AB  - The role of oxidative stress in alcoholic liver disease and cytokeratin aggresome
      formation is the focus of this in vitro study. HepG2 cells transduced to over
      express CYP2E1 (E47) and control HepG2 cells (C34) were first treated with
      arachidonic acid, then Fe-NAT, and finally with ethanol. In the E47 ethanol
      treated cells, CYP2E1 was induced and a higher level of reactive oxygen species
      and carbonyl proteins were generated. The proteasome activity decreased
      significantly in the E47 ethanol-treated cells. This inhibition was prevented
      when CYP2E1 was inhibited by DAS. Microarray analysis showed gene expression down
      regulation of the proteasome subunit, as well as ubiquitin pathway proteins in
      the E47 ethanol-treated cells. 4-Hydroxynonenal (4-HNE) adducts were increased in
      the E47 cells treated with ethanol. Furthermore, the immunoprecipitated 4-HNE
      modified proteins from these cells stained positive with antibodies to the
      proteasome subunit alpha 6. These results indicate that the ethanol induced
      CYP2E1 generates oxidative stress that is responsible for the decrease in
      proteasome activity. Cytokeratin 8 and 18 were induced by ethanol treatment of
      E47 cells and polyubiquitinated forms of these proteins were found in the
      polyubiquitin smear upon Western blots analysis. Cytokeratin aggresomes and
      Mallory body-like inclusions formed in the ethanol-treated E47 cells, indicating
      that the ubiquitinated cytokeratins accumulated as a result of the inhibition of
      the proteasome by ethanol treatment when oxidation of ethanol induced oxidative
      stress. This is the first report where ethanol caused Mallory body-like
      cytokeratin inclusions in transformed human liver cells in vitro.

PMID- 17034789
TI  - Alpha-complementation as a probe for dual localization of mitochondrial proteins.
AB  - There are a growing number of proteins which are reported to reside in multiple
      compartments within the eukaryotic cell. However, lack of appropriate methods
      limits our knowledge on the true extent of this phenomenon. In this study, we
      demonstrate a novel application of beta-galactosidase alpha-complementation to
      study dual distribution of proteins in yeast cells. Using a simple colony color
      phenotype, we show that alpha-complementation depends on co-compartmentalization
      of alpha and omega fragments and exploit this to probe dual localization of
      proteins between the cytosol and mitochondria in yeast. The quality of our assay
      was assessed by analysis of the known dual targeted enzyme fumarase and several
      mutant derivatives, which are exclusively localized to one or the other of these
      subcellular compartments. Addition of the alpha fragment did not abolish the
      enzymatic activity of the tagged proteins nor did it affect their localization.
      By examining 10 yeast gene products for distribution between the cytosol and the
      mitochondria, we demonstrate the potential of alpha-complementation to screen the
      mitochondrial proteome for dual distribution. Our data indicate the distribution
      of two uncharacterized proteins--Bna3 and Nif3--between the cytosol and the
      mitochondria.

PMID- 17034790
TI  - Muscle-derived but not centrally derived transgene GDNF is neuroprotective in
      G93A-SOD1 mouse model of ALS.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor
      for motoneurons (MNs), and is considered a potential agent for the treatment of
      amyotrophic lateral sclerosis (ALS) and other MN diseases. The effectiveness of
      GDNF may depend significantly upon its route of delivery to MNs. In this study we
      tested the neuroprotective effects of target-derived and centrally derived GDNF
      in the G93A-SOD1 mouse model of ALS using a transgenic approach. We found that
      overexpression of GDNF in the skeletal muscle (Myo-GDNF mice) significantly
      delayed the onset of disease and increased the life span of G93A-SOD1 mice by 17
      days. The duration of disease also increased by 8.5 days, indicating that GDNF
      slowed down the progression of disease. Locomotor performance in Myo-GDNF/G93A
      SOD1 mice was also significantly improved. The behavioral improvement correlated
      well with anatomical and histological data. We demonstrated that muscle-derived
      GDNF resulted in increased survival of spinal MNs, and twice as many MNs survived
      in end-stage double transgenic mice compared to end-stage G93A-SOD1 mice. Muscle
      derived GDNF also had profound effects on muscle innervation and axonal
      degeneration. Significantly higher numbers of completely or partially innervated
      NMJs and large caliber myelinated axons were found in double transgenic mice. In
      contrast, we demonstrated that overexpression of GDNF in astrocytes in the CNS
      (GFAP-GDNF mice) failed to demonstrate any neuroprotective effects in G93A-SOD1
      mice both on behavioral and histological levels. These data indicate that
      retrograde transport and signaling of GDNF is more physiological and effective
      for ALS treatment than anterogradely transported GDNF.

PMID- 17034791
TI  - Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor
      cells through bHLH proteins and Nurr1.
AB  - The production of dopamine (DA) neurons from neural progenitor cells (NPC) is of
      particular interest as these neurons degenerate in Parkinson's disease. Here, we
      report that the characteristics of NPC from the ventral midbrain (NPC(VM)) and
      the striatum (NPC(STR)) are intrinsically determined. A detailed analysis of the
      VM during development revealed Ngn2 and Mash1 expression in a DA progenitor
      domain. Interestingly, over-expression of either Ngn2 or Mash1 induced
      neurogenesis from expanded NPC(VM). Whereas Ngn2 inhibited cell division and the
      production of neurons even in the presence of mitogens, Mash1 allowed the
      progenitors to divide while retaining neurogenic potential. However, none of the
      new neurons derived by over-expressing Ngn2 or Mash1 were positive for DA
      neuronal markers such as tyrosine hydroxylase. Nurr1 over-expression increased TH
      levels in a dose-dependant manner within both neurons and glia, suggesting a non
      neuronal-specific activation of this enzyme by Nurr1. Double infection with Nurr1
      and either Ngn2 or Mash1 resulted in the production of small numbers of TH+
      neurons, which were larger in size when derived from NPC(VM) compared to
      NPC(STR). These data provide proof of concept that over-expression of multiple
      transcription factors can drive the fate of NPC first towards neurons, and then
      towards the DA phenotype. However, further factors may be required to generate
      fully functional DA neurons.

PMID- 17034792
TI  - PCR detection of Anaplasma platys in blood and tissue of dogs during acute phase
      of experimental infection.
AB  - Four dogs were experimentally infected with Anaplasma platys to determine changes
      in real-time TaqMan PCR detection in blood and tissue, microscopically detectable
      parasitemia, and platelet concentrations during the first 28 days of infection.
      Buffy-coat blood cells were PCR positive for A. platys DNA at 4 days after
      inoculation and remained positive in all dogs until day 14. Marked
      thrombocytopenia and low parasitemia occurred in dogs during that initial period.
      During 17 and 28 days post-inoculation, the PCR results on buffy-coat blood cells
      were intermittently negative in each dog with marked thrombocytopenia and no
      microscopic evidence of parasitemia. Bone marrow and splenic aspirates collected
      from the A. platys-infected dogs were tested by real-time TaqMan PCR. Two dogs
      were PCR positive in spleen and marrow at 28 days post-inoculation, when PCR
      results for buffy-coat blood cells were negative. Spleen and/or bone marrow
      samples should be considered as additional samples for PCR testing of dogs,
      particularly when blood samples are PCR negative during the acute phase of A.
      platys infection.

PMID- 17034794
TI  - Psychological stressors as a model of maternal adversity: diurnal modulation of
      corticosterone responses and changes in maternal behavior.
AB  - Maternal adversity is associated with long-lasting consequences on cognitive
      development, behavior and physiological responses in rat offspring. Few studies
      have examined whether repeated maternal stress produces repeated activation of
      the hypothalamus-pituitary-adrenal (HPA) axis in mothers and whether it modifies
      maternal behavior. Here, we tested a novel model of perinatal stress using
      repeated exposure to "purely" psychological stressors throughout the gestation
      and lactation periods in rats. We first tested the diurnal influences of repeated
      1-h strobe light exposure on maternal corticosterone secretion. Despite the
      hyporesponsiveness to stress documented in late pregnant and lactating mothers,
      we observed an enhanced response to strobe light in the afternoon compared to the
      morning in stressed mothers during lactation. Next, dams were exposed to 24-h
      forced foraging followed by 10-h wet bedding during the diurnal peak of
      corticosterone secretion. Although no corticosterone responses to forced foraging
      and wet bedding were observed, the combination of both stressors had a
      significant effect on maternal behavior. Mother-pup interactions were
      significantly altered during the first 8 days of lactation. Taken together, these
      findings suggest that lactating mothers maintain responsiveness to specific and
      repeated psychological stressors, in particular at the time of the diurnal peak
      in corticosterone secretion. Depending on the stressor applied, either
      neuroendocrine activation or changes in maternal behavior might be important
      determinants of the long-term consequences in the offspring. The combination of
      forced foraging, wet bedding and strobe light might represent a novel model of
      mild maternal adversity using "purely" psychological stressors.

PMID- 17034793
TI  - A novel analytical method for in vivo phosphate tracking.
AB  - Genetically-encoded fluorescence resonance energy transfer (FRET) sensors for
      phosphate (P(i)) (FLIPPi) were engineered by fusing a predicted Synechococcus
      phosphate-binding protein (PiBP) to eCFP and Venus. Purified fluorescent
      indicator protein for inorganic phosphate (FLIPPi), in which the fluorophores are
      attached to the same PiBP lobe, shows P(i)-dependent increases in FRET
      efficiency. FLIPPi affinity mutants cover P(i) changes over eight orders of
      magnitude. COS-7 cells co-expressing a low-affinity FLIPPi and a Na(+)/P(i) co
      transporter exhibited FRET changes when perfused with 100 microM P(i),
      demonstrating concentrative P(i) uptake by PiT2. FLIPPi sensors are suitable for
      real-time monitoring of P(i) metabolism in living cells, providing a new tool for
      fluxomics, analysis of pathophysiology or changes of P(i) during cell migration.

PMID- 17034795
TI  - gamma-Glutamyltransferase predicts cardiovascular death among Japanese women.
AB  - The clinical importance of gamma-glutamyltransferase (GGT) has recently been
      debated. Although some studies have suggested that the relationship between GGT
      and cardiovascular disease (CVD) mortality is independent of alcohol consumption,
      to our knowledge no studies have reported the relationship between GGT and CVD
      mortality in never-drinker subgroups. Since Japanese women are known to have a
      lower prevalence of alcohol consumption, we examined whether GGT predicts CVD
      mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese
      women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82
      CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of
      women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality
      compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence
      interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive
      relationship was unchanged in the never-drinkers subgroup (HR for log-transformed
      continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were
      observed in men. GGT displays a strong positive association with CVD mortality
      among Japanese women, for whom the prevalence of ever-drinkers is very low.
      Exploring the significance and biological mechanisms of GGT might provide useful
      insights into CVD prevention.

PMID- 17034796
TI  - Suprascapular nerve block results in a compensatory increase in deltoid muscle
      activity.
AB  - A balance exists between the deltoid and rotator cuff contribution to arm
      elevation. Both cadaver and computer models have predicted an increase in deltoid
      muscle force with dysfunction of the rotator cuff. The goal of the present study
      was to verify this phenomenon in vivo by examining the effects of paralysis of
      the supraspinatus and infraspinatus muscles with a suprascapular nerve block on
      the electrical activity of seven shoulder muscles. Electromyographic data were
      collected before and after the administration of the block. The block resulted in
      a significant increase in muscle activity for all heads of the deltoid, with a
      higher percentage increase noted at lower elevation angles. Although the deltoid
      activity was reduced as the subjects recovered from the block, even low levels of
      cuff dysfunction were found to result in increased deltoid activity. These
      results suggest that even small disruptions in the normal function of some
      rotator cuff muscles (e.g., due to fatigue or impingement syndrome), may result
      in an increase in deltoid activity. It is possible that such compensation may
      result in higher superior loads at the glenohumeral joint, possibly increasing
      the risk of tendon damage.

PMID- 17034797
TI  - Three-dimensional computer simulation of radiostereometric analysis (RSA) in
      distal radius fractures.
AB  - Physical phantom models have conventionally been used to determine the accuracy
      and precision of radiostereometric analysis (RSA) in various orthopaedic
      applications. Using a phantom model of a fracture of the distal radius it has
      previously been shown that RSA is a highly accurate and precise method for
      measuring both translation and rotation in three-dimensions (3-D). The main
      shortcoming of a physical phantom model is its inability to mimic complex 3-D
      motion. The goal of this study was to create a realistic computer model for
      preoperative planning of RSA studies and to test the accuracy of RSA in measuring
      complex movements in fractures of the distal radius using this new model. The 3-D
      computer model was created from a set of tomographic scans. The simulation of the
      radiographic imaging was performed using ray-tracing software (POV-Ray). RSA
      measurements were performed according to standard protocol. Using a two-part
      fracture model (AO/ASIF type A2), it was found that for simple movements in one
      axis, translations in the range of 25microm-2mm could be measured with an
      accuracy of +/-2microm. Rotations ranging from 16 degrees to 2 degrees could be
      measured with an accuracy of +/-0.015 degrees . Using a three-part fracture model
      the corresponding values of accuracy were found to be +/-4microm and +/-0.031
      degrees for translation and rotation, respectively. For complex 3-D motion in a
      three-part fracture model (AO/ASIF type C1) the accuracy was +/-6microm for
      translation and +/-0.120 degrees for rotation. The use of 3-D computer modelling
      can provide a method for preoperative planning of RSA studies in complex
      fractures of the distal radius and in other clinical situations in which the RSA
      method is applicable.

PMID- 17034798
TI  - Prediction of strength and strain of the proximal femur by a CT-based finite
      element method.
AB  - Hip fractures are the most serious complication of osteoporosis and have been
      recognized as a major public health problem. In elderly persons, hip fractures
      occur as a result of increased fragility of the proximal femur due to
      osteoporosis. It is essential to precisely quantify the strength of the proximal
      femur in order to estimate the fracture risk and plan preventive interventions.
      CT-based finite element analysis could possibly achieve precise assessment of the
      strength of the proximal femur. The purpose of this study was to create a
      simulation model that could accurately predict the strength and surface strains
      of the proximal femur using a CT-based finite element method and to verify the
      accuracy of our model by load testing using fresh frozen cadaver specimens.
      Eleven right femora were collected. The axial CT scans of the proximal femora
      were obtained with a calibration phantom, from which the 3D finite element models
      were constructed. Materially nonlinear finite element analyses were performed.
      The yield and fracture loads were calculated, while the sites where elements
      failed and the distributions of the principal strains were determined. The strain
      gauges were attached to the proximal femoral surfaces. A quasi-static compression
      test of each femur was conducted. The yield loads, fracture loads and principal
      strains of the prediction significantly correlated with those measured (r=0.941,
      0.979, 0.963). Finite element analysis showed that the solid elements and shell
      elements in undergoing compressive failure were at the same subcapital region as
      the experimental fracture site.

PMID- 17034799
TI  - Mechanics of arterial subfailure with increasing loading rate.
AB  - Arterial subfailure leads to delayed symptomatology and high morbidity and
      mortality rates, particularly for the thoracic aorta and carotid arteries.
      Although arterial injuries occur during high-velocity automotive collisions,
      previous studies of arterial subfailure focused on quasi-static loading. This
      investigation subjected aortic segments to increasing loading rates to quantify
      effects on elastic, subfailure, and ultimate vessel mechanics. Sixty-two
      specimens were axially distracted, and 92% demonstrated subfailure before
      ultimate failure. With increasing loading rate, stress at initial subfailure and
      ultimate failure significantly increased, and strain at initial subfailure and
      ultimate failure significantly decreased. Present results indicate increased
      susceptibility for arterial subfailure and/or dissection under higher-rate
      extension. According to the present results, automotive occupants are at greater
      risk of arterial injury under higher velocity impacts due to greater body segment
      motions in addition to decreased strain tolerance to subfailure and catastrophic
      failure.

PMID- 17034800
TI  - Preparation of dye-ligand affinity chromatographic packings based on monodisperse
      poly(glycidylmethacrylate-co-ethylenedimethacrylate) beads and their
      chromatographic properties.
AB  - Monodisperse porous particles, poly(glycidylmethacrylate-co
      ethylenedimethacrylate), P(GMA-EDMA) beads with diameter of 7 microm were
      prepared by a single-step swelling and polymerization method. The polymer
      particles were advantaged through immobilization of Procion Bule MX-R, which was
      incubated by epichlorohydrin via the epoxide groups on the particles surface. The
      Procion Bule MX-R-immobilized P(GMA-EDMA) beads were mechanically stable and
      acted as the rigid matrix for column chromatography in HPLC mode. The
      chromatographic properties of the dye-ligand affinity chromatographic stationary
      phase for biopolymers separation are discussed. This affinity column has
      advantages of enabling biopolymer separation, high efficiency and low
      backpressure. Lysozyme and BSA were fast separated within 10min using this
      affinity column. The column was also used for the purification of lysozyme from
      chicken egg white.

PMID- 17034801
TI  - On-line derivatization gas chromatography with furan chemical ionization tandem
      mass spectrometry for screening of amphetamines in urine.
AB  - A simple alternative method with minimal sample pretreatment is investigated for
      screening of amphetamines in small volume (using only 20 microL) of urine sample.
      The method is sensitive and selective. The method uses gas chromatography (GC)
      direct sample introduction (DSI) for on-line derivatization (acylation) of
      amphetamines to improve sensitivity. Furan as chemical ionization (CI) reagent in
      conjunction with tandem mass spectrometry (MS/MS) is used to improve selectivity.
      Low background with sharp protonated molecular ion peaks of analytes is the
      evidence of improvement in sensitivity and selectivity. Blank urine samples
      spiked with known amounts of amphetamine, methamphetamine, 3,4
      methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4
      methylenedioxyethylamphetamine is analyzed. Selected ion monitoring of the
      characteristic product ions (m/z 119+136+150+163) using furan CI-MS/MS in
      positive ion mode is used for quantification. Limits of detection (LOD) between
      0.4 and 1.0 ng mL(-1) and limits of quantitation (LOQ) between 1.0 and 2.0 ng mL(
      1) are established. Linear response over the range of 1-1000 ng mL(-1)
      (r(2)>0.997) is observed for all analytes, except for methamphetamine (2.0-1000
      ng mL(-1)). Good accuracy between 86 and 113% and precision ranging from 4 to 18%
      is obtained. The method is also tested on real samples of urine from suspected
      drug abusers. This method could be used for screening and determination of
      amphetamines in urine samples, however needs additional work for full validation.

PMID- 17034802
TI  - New findings for in-gel digestion accelerated by high-intensity focused
      ultrasound for protein identification by matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry.
AB  - New findings in sample treatment based on high-intensity focused ultrasound
      (HIFU) for protein digestion after polyacrylamide gel electrophoresis separation
      are presented. The following variables were studied: (i) sample volume; (ii)
      sonotrode diameter; (iii) previous protein denaturation; (iv) cooling; (v) enzyme
      concentration; and (vi) protein concentration. Results showed that positive
      protein identification could be done after protein separation by gel
      electrophoresis through peptide mass fingerprint (PMF) in a volume as low as 25
      microL. The time needed was less than 2 min and no cooling was necessary. The
      importance of the sonotrode diameter was negligible. On the other hand, protein
      denaturation before sonication was a trade-off for the success of procedure here
      described. The protein coverage was raised from 5 to 30%, and the number of
      peptides matching the proteins was also increased in a percentage ranging 10-100%
      when the classical overnight treatment is compared with the proposed HIFU
      procedure. The minimum amount of protein that can be identified using the HIFU
      sample treatment by matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS) was 0.06 microg. The lower concentration of
      trypsin successfully used to obtain an adequate protein digestion was 3.6
      microg/mL.

PMID- 17034803
TI  - Modeling and simulation of protein uptake in cation exchanger visualized by
      confocal laser scanning microscopy.
AB  - Confocal laser scanning microscopy (CLSM) has been extensively applied in the
      area of protein chromatography to investigate the uptake mechanism of protein in
      adsorbents. However, due to the light attenuation in the deeper layers of a
      specimen, quantitative analysis using CLSM data is still far from reality. In
      this work, an attenuation equation for describing the darkening of the CLSM image
      in the deeper scanning layers was developed. Bovine serum albumin (BSA)
      adsorption to SP Sepharose FF was performed by batch adsorption and micro-column
      chromatography on which protein concentration in single absorbents were
      visualized by CLSM. The parameters in the equation were estimated by fitting it
      to the fluorescence intensity profiles obtained at adsorption equilibrium, and
      then the equation was used to simulate the effect caused by the light scattering
      and absorption. CLSM analysis demonstrated that BSA adsorption to SP Sepharose FF
      followed the shrinking core pattern and was predicted reasonably well by the pore
      diffusion model in combination with the attenuation equation. By comparison of
      the CLSM data with the simulations, it shows that the attenuation equation was
      useful to demonstrate the validity of an intraparticle mass transport model for
      the estimation of intraparticle protein concentration profiles.

PMID- 17034804
TI  - Aromatic resin characterisation by gas chromatography-mass spectrometry. Raw and
      archaeological materials.
AB  - An analytical procedure based on alkaline hydrolysis, solvent extraction and
      trimethyl-silylation followed by gas chromatography-mass spectrometry (GC-MS)
      analysis was used to study the chemical composition of benzoe and storax resins,
      water-insoluble exudates of trees of the Styrax and Liquidambar genus. They are
      chemically characterised by having aromatic acids, alcohols and esters as their
      main components and are thus known as aromatic and/or balsamic resins. This
      analytical procedure allowed us to characterise the main components of the two
      resins and, even though cinnamic acid is the main component of both the resins,
      the presence of other characteristic aromatic compounds and triterpenes permitted
      us to distinguish between the two materials. All the compounds identified in
      benzoe resin were detected in an archaeological organic residue from an Egyptian
      ceramic censer (fifth to seventh centuries a.d.), thus proving that this resin
      was used as one of the components of the mixture of organic materials burned as
      incense. These results provide the first chemical evidence of the presence of
      benzoe resin in an archaeological material from Mediterranean area.

PMID- 17034805
TI  - High sensitivity separation and detection of heparan sulfate disaccharides.
AB  - Eight Delta-disaccharide standards from heparan sulfate/heparin were derivatized
      with the fluorophore 4,4-difluoro-5,7- dimethyl-4-bora-3a,4a-diaza-s-indacene-3
      propionic acid, hydrazide (BODIPY) via formation of a Schiff's base and separated
      using HPAEC on a Propac PA1 column with a linear salt gradient and isocratic 150
      mM NaOH. Detection was with an in-line fluorescence detector. The standard
      deviation (sigma(n-1)) in retention times were 0.7-2% over nine runs. The limit
      of detection, was 100 fmol (100 x 10(-15)mol) of BODIPY labeled Delta
      disaccharides, representing considerably improved detection compared to other
      fluorophore labeled derivatives and, unlike these, required no further
      purification steps. Separation and improved detection of BODIPY-Delta
      disaccharide conjugates will assist the structural analysis of HS and the
      development of improved sequencing methodologies.

PMID- 17034806
TI  - Equilibrium and dynamic aspects of dodecyltrimethylammonium bromide adsorption at
      the air/water interface in the presence of lambda-carrageenan.
AB  - In this work we present equilibrium and dynamic surface tension together with
      dilational elasticity data for dodecyltrimethylammonium bromide in the presence
      of lambda-carrageenan, a sulfated polysaccharide extracted from algae. The
      critical aggregation concentration and (CAC) and critical micellar concentration
      CMC of the mixed system were determined and shown to have a direct influence on
      the elasticity modulus. The behavior of the adsorption kinetics was shown to be
      dependent on the surfactant to polyelectrolyte charge ratio or excess species in
      the bulk solution.

PMID- 17034807
TI  - Aggregation and gelation kinetics of fumed silica-ethanol suspensions.
AB  - The kinetics of aggregation and gelation of fumed silica suspended in ethanol
      were investigated as a function of volume fraction. At low particle
      concentrations, gelation is well described by aggregation into a primary minimum
      arising from hydrogen bonding and dispersion forces. The gelation is extremely
      slow due to an energetic barrier (approximately 25 kT) in the interparticle
      potential associated with solvation forces. The solvation forces also contribute
      to the formation of a secondary minimum in the interparticle potential. The depth
      of this minimum (approximately 3 kT) is sufficient that, at a critical particle
      concentration, long-range diffusion is arrested due to the short-range
      attractions and the cooperative nature of particle interactions, as described by
      mode coupling theory. The presence of the secondary minimum is also observed in
      the microstructure of the gels studied using X-ray scattering. These observations
      reinforce the importance of understanding the role of solvent-particle
      interactions in manipulating suspension properties.

PMID- 17034808
TI  - Lysozyme binding onto cat-anionic vesicles.
AB  - Mixing aqueous sodium dodecylsulfate with cetyltrimethylammonium bromide
      solutions in mole ratios close to (1.7/1.0) allows the formation of cat-anionic
      vesicles with an excess of negative charges on the outer surface. The vesicular
      dispersions are mixed with lysozyme, and interact electrostatically with the
      positive charges on the protein, forming lipo-plexes. Dielectric relaxation, zeta
      potential, and light scattering indicate the occurrence of interactions between
      vesicles and the protein. According to CD, the vesicle-adsorbed protein retains
      its native conformation. Binding and surface saturation, inferred by dielectric
      relaxation and zeta-potential, fulfil a charge neutralisation stoichiometry.
      Adsorbed lysozyme promotes the vesicle clustering and is concomitant with the
      lipo-plexes flocculation. Above the charge neutralisation threshold, lysozyme in
      excess remains dispersed in molecular form. Attempts were made to determine in
      what conditions protein release from the vesicles occurs. Accordingly, the full
      neutralisation of sodium dodecylsulfate in excess by cetyltrimethylammonium
      bromide ensures the lipo-plexes break-up, the precipitation of the mixed
      surfactants and the protein release in native form.

PMID- 17034809
TI  - The adsorption behavior of crystal violet in functionalized sporopollenin
      mediated column arrangements.
AB  - The adsorption behavior of Crystal Violet (CV) on a sporopollenin-based solid
      phase, carboxylated diaminoethane sporopollenin (CDAE-S), was investigated under
      column conditions, and the obtained breakthrough profiles were used in
      evaluations and quantifications. The adsorption capacity of the CDAE-S was
      observed to be considerably higher than that of diaminoethane sporopollenin (DAE
      S), revealing the importance of electrostatic interactions and carboxyl groups in
      the adsorption of CV on the CDAE-S. The binding of CV on the DAE-S was found to
      be a typical nonspecific adsorption, whilst cation-exchange was proposed as the
      main mechanism for monolayer adsorption of CV on the CDAE-S. Hence in the present
      study, the cation-exchange is suggested as an effective process for removal and
      recovery of CV from aqueous effluents, and in view of the pH point of zero charge
      matter, multifunctionality of the CDAE-S is discussed in detail, and various
      application possibilities based on "aminocarboxylic acid" functionality are also
      drawn.

PMID- 17034810
TI  - Otarine Herpesvirus-1, not papillomavirus, is associated with endemic tumours in
      California sea lions (Zalophus californianus).
AB  - The purpose of this study was to determine if Otarine Herpesvirus-1 (OtHV-1) is
      associated with the presence of urogenital carcinomas in California sea lions.
      Polymerase chain reaction (PCR) analysis with primers specific for OtHV-1 was
      used to compare the prevalence of OtHV-1 infection in 15 sea lions affected by
      urogenital carcinoma with that of age-matched and juvenile tumour-free animals,
      and animals with tumours of non-urogenital origin. The herpesvirus was more
      prevalent (100%) and more widespread in the 15 animals with urogenital carcinoma
      than in 25 control animals, and was most often found in the urogenital tissue
      (vagina and prostate) and in the draining lymph nodes. Moreover, OtHV-1 DNA was
      not found in any juvenile animal, or in the neoplastic tissues of animals with
      non-urogenital tumours. Papillomavirus-specific PCR analysis of urogenital
      carcinoma tissues detected papillomavirus sequences in only one carcinomatous
      tissue. Further studies are needed to determine if OtHV-1 contributes to
      oncogenesis in the California sea lion; these data show, however, that OtHV-1 is
      associated with urogenital carcinomas, is preferentially present in urogenital
      tissues, and may be sexually transmitted. Papillomaviruses, which are known to
      contribute to urogenital tumours in other species, did not appear to be
      associated with the sea lion carcinomas.

PMID- 17034811
TI  - The thyroid gland in bottlenose dolphins (Tursiops truncatus) from the Texas
      coast of the Gulf of Mexico: normal structure and pathological changes.
AB  - Fresh thyroid glands (n=60) from Atlantic bottlenose dolphins that died after
      stranding along the Texas coast between 1991 and 2005 were examined. Organ weight
      ranged from 11 g in a neonate (length 109 cm) to 58 g in a large (249 cm) male.
      More typical weights were 25-45 g (mean=30.6 g). Glands tended to be larger in
      pregnant and lactating females (mean 37.4 g; n=5) than in non-pregnant animals of
      comparable size. In infancy, the gland tended to be compact, relatively
      homogeneous, and sometimes partly lobular, but with advancing age it became more
      lobular, the lobules being defined by fibrous bands. In one 8-year-old female
      (233 cm), and in a large male (295 cm) aged>25 years the gland was represented by
      a cluster of lobules. Lobulation was not necessarily accompanied by increased
      weight, distinguishing it from hyperplasia. With age, variation in follicle size
      and colloid density tended to increase. Two animals (3%) had adenomas and five
      (8%) had discrete hyperplastic nodules, not to be confused with lobulation. Five
      (8%) had macroscopically identifiable colloid-filled cysts (1-4 mm in diameter).
      Nine animals (15%) had squamous cysts (4-15 mm) containing creamy white fluid.
      Other abnormalities included patchy or diffuse interstitial fibrosis (six cases,
      10%) amyloidosis (two cases), thyroiditis (one case) and vasculitis (one case).
      No malignant neoplasms were found. Cells presumed to be C cells (light cells,
      parafollicular cells) were identified immunohistochemically with synaptophysin
      antibody.

PMID- 17034812
TI  - Word acquisition, retention, and transfer: findings from contextual and isolated
      word training.
AB  - Successful reading instruction entails not only acquiring new words but also
      remembering them after training has finished and accessing their word-specific
      representations when they are encountered in new text. We report two studies
      demonstrating that acquisition, retention, and transfer of unfamiliar words were
      affected differentially by isolated word and context training. Materials were
      individualized to include only those words that average readers in second grade
      were unable to name in context. Different words were trained in each condition;
      context training presented words in stories, and isolated word training presented
      words on flashcards. Together, the studies show that context training promotes
      word acquisition beyond that experienced from reading words in isolation.
      Contrary to the prevailing opinion, memory performance for words trained in
      context and in isolation did not differ; children demonstrated excellent
      retention over an 8-day interval in both conditions. Finally, transfer was
      maximized when the congruency between training and testing was high. Therefore,
      when reading trained words in novel circumstances, the best method of training
      was mediated by the transfer task employed at test.

PMID- 17034813
TI  - Simultaneous detection of a cell surface antigen and apoptosis by microwave
      sensitized TUNEL assay on paraffin sections.
AB  - The TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)
      technique has been described as a sensitive method for detection of apoptotic
      nuclei in tissues and preferential staining of apoptotic strand breaks. Short
      term microwave pre-treatment, a non-enzymatic pre-treatment technique of antigen
      retrieval, has been demonstrated to optimize the TUNEL method for in situ
      detection of apoptotic cells in formalin-fixed paraffin-embedded tissue sections.
      In the present study, we sensitized internal mammary artery sections by short
      term microwave pre-treatment and used a two-step indirect enzymatic method to
      gain as an end product differentially stained cells, namely TUNEL-positive cells
      and these positive for the surface marker von Willebrand factor (vWF). This
      technique enables to clearly distinguish between apoptotic, non-apoptotic and vWF
      positive cells that are phenotypic for endothelial cells. Phenotypic
      identification of cells is simplified by double staining with cell surface
      markers. This rapid, sensitive and reproducible technique allows simultaneous
      detection of DNA fragmentation and phenotypic markers in the same paraffin
      embedded human tissue section.

PMID- 17034814
TI  - Primary culture of hemocytes from the Caribbean spiny lobster, Panulirus argus,
      and their susceptibility to Panulirus argus Virus 1 (PaV1).
AB  - Primary cultures of hemocytes from the Caribbean spiny lobster Panulirus argus
      were developed for studies on the in vitro propagation of Panulirus argus Virus 1
      (PaV1). A modified Leibovitz L-15 medium supported the best survival of hemocytes
      in in vitro primary cultures. However, degradation of the cultures occurred
      rapidly in the presence of granulocytes. A Percoll step gradient was used to
      separate hemocytes into three subpopulations enriched in hyalinocytes,
      semigranulocytes, and granulocytes, respectively. When cultured separately,
      hyalinocytes and semigranulocytes maintained higher viability ( approximately
      80%) after 18 days incubation compared with granulocytes, which degraded over 2-3
      days. Susceptibility of the cell types was investigated in challenge studies with
      PaV1. Hyalinocytes and semigranulocytes were susceptible to PaV1. Cytopathic
      effects (CPE) were observed as early as 12h post-inoculation, and as the
      infection progressed, CPE became more apparent, with cell debris and cellular
      exudates present in inoculated cultures. Cell lysis was noticeable within 24h of
      infection. The presence of virus within cells was further confirmed by in situ
      hybridization using a specific DNA probe. The probe gave a unique staining
      pattern to cells infected with PaV1 24-h post-inoculation. Cells in the control
      treatment were intact and negative to hybridization. This assay was further
      applied to the quantification of infectious virus in hemolymph using a 50% tissue
      culture infectious dose assay (TCID(50)) based on CPE. These tools will now allow
      the quantification of PaV1 using established culture-based methods.

PMID- 17034815
TI  - Cognate ligand domain mapping for enzymes.
AB  - Here, we present an automatic assignment of potential cognate ligands to domains
      of enzymes in the CATH and SCOP protein domain classifications on the basis of
      structural data available in the wwPDB. This procedure involves two steps;
      firstly, we assign the binding of particular ligands to particular domains;
      secondly, we compare the chemical similarity of the PDB ligands to ligands in
      KEGG in order to assign cognate ligands. We find that use of the Enzyme
      Commission (EC) numbers is necessary to enable efficient and accurate cognate
      ligand assignment. The PROCOGNATE database currently has cognate ligand mapping
      for 3277 (4118) protein structures and 351 (302) superfamilies, as described by
      the CATH and (SCOP) databases, respectively. We find that just under half of all
      ligands are only and always bound by a single domain, with 16% bound by more than
      one domain and the remainder of the ligands showing a variety of binding modes.
      This finding has implications for domain recombination and the evolution of new
      protein functions. Domain architecture or context is also found to affect
      substrate specificity of particular domains, and we discuss example cases. The
      most popular PDB ligands are all found to be generic components of
      crystallisation buffers, highlighting the non-cognate ligand problem inherent in
      the PDB. In contrast, the most popular cognate ligands are all found to be
      universal cellular currencies of reducing power and energy such as NADH, FADH2
      and ATP, respectively, reflecting the fact that the vast majority of enzymatic
      reactions utilise one of these popular co-factors. These ligands all share a
      common adenine ribonucleotide moiety, suggesting that many different domain
      superfamilies have converged to bind this chemical framework.

PMID- 17034816
TI  - A novel lysine-rich domain and GTP binding motifs regulate the nucleolar
      retention of human guanine nucleotide binding protein, GNL3L.
AB  - A variety of G-proteins and GTPases are known to be involved in nucleolar
      function. We describe here a new evolutionarily conserved putative human GTPase,
      guanine nucleotide binding protein-like 3-like (GNL3L). Genes encoding proteins
      related to GNL3L are present in bacteria and yeast to metazoa and suggests its
      critical role in development. Conserved domain search analysis revealed that the
      GNL3L contains a circularly permuted G-motif described by a G5-G4-G1-G2-G3
      pattern similar to the HSR1/MMR1 GTP-binding protein subfamily. Highly conserved
      and critical residues were identified from a three-dimensional structural model
      obtained for GNL3L using the crystal structure of an Ylqf GTPase from Bacillus
      subtilis. We demonstrate here that GNL3L is transported into the nucleolus by a
      novel lysine-rich nucleolar localization signal (NoLS) residing within 1-50 amino
      acid residues. NoLS identified here is necessary and sufficient to target the
      heterologous proteins to the nucleolus. We show for the first time that the
      lysine-rich targeting signal interacts with the nuclear transport receptor,
      importin-beta and transports GNL3L into the nucleolus. Interestingly, depletion
      of intracellular GTP blocks GNL3L accumulation into the nucleolar compartment.
      Furthermore, mutations within the G-domains alter the GTP binding ability of
      GNL3L and abrogate wild-type nucleolar retention even in the presence of
      functional NoLS, suggesting that the efficient nucleolar retention of GNL3L
      involves activities of both basic NoLS and GTP-binding domains. Collectively,
      these data suggest that GNL3L is composed of distinct modules, each of which
      plays a specific role in molecular interactions for its nucleolar retention and
      subsequent function(s) within the nucleolus.

PMID- 17034817
TI  - Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and
      enzyme-NADP(H) binary complex): identification of molecular determinants
      responsible for the unique 17alpha-reductive activity of this enzyme.
AB  - Very recently, the mouse 17alpha-hydroxysteroid dehydrogenase (m17alpha-HSD), a
      member of the aldo-keto reductase (AKR) superfamily, has been characterized and
      identified as the unique enzyme able to catalyze efficiently and in a
      stereospecific manner the conversion of androstenedione (Delta4) into
      epitestosterone (epi-T), the 17alpha-epimer of testosterone. Indeed, the other
      AKR enzymes that significantly reduce keto groups situated at position C17 of the
      steroid nucleus, the human type 3 3alpha-HSD (h3alpha-HSD3), the human and mouse
      type 5 17beta-HSD, and the rabbit 20alpha-HSD, produce only 17beta-hydroxy
      derivatives, although they possess more than 70% amino acid identity with
      m17alpha-HSD. Structural comparisons of these highly homologous enzymes thus
      offer an excellent opportunity of identifying the molecular determinants
      responsible for their 17alpha/17beta-stereospecificity. Here, we report the
      crystal structure of the m17alpha-HSD enzyme in its apo-form (1.9 A resolution)
      as well as those of two different forms of this enzyme in binary complex with
      NADP(H) (2.9 A and 1.35 A resolution). Interestingly, one of these binary complex
      structures could represent a conformational intermediate between the apoenzyme
      and the active binary complex. These structures provide a complete picture of the
      NADP(H)-enzyme interactions involving the flexible loop B, which can adopt two
      different conformations upon cofactor binding. Structural comparison with binary
      complexes of other AKR1C enzymes has also revealed particularities of the
      interaction between m17alpha-HSD and NADP(H), which explain why it has been
      possible to crystallize this enzyme in its apo form. Close inspection of the
      m17alpha-HSD steroid-binding cavity formed upon cofactor binding leads us to
      hypothesize that the residue at position 24 is of paramount importance for the
      stereospecificity of the reduction reaction. Mutagenic studies have showed that
      the m17alpha-HSD(A24Y) mutant exhibited a completely reversed stereospecificity,
      producing testosterone only from Delta4, whereas the h3alpha-HSD3(Y24A) mutant
      acquires the capacity to metabolize Delta4 into epi-T.

PMID- 17034818
TI  - Dementia with Lewy bodies.
AB  - Advanced Parkinson's disease (PD) is frequently associated with dementia. The
      pathogenesis of this dementia is complex, related to deficiency of several
      biogenic amines and cortical Lewy body deposition, as well as co-existent age
      related brain changes, both of the Alzheimer type and vascular. However,
      degeneration of the cholinergic neurons in the nucleus basalis of Meynert may
      have an important contribution to the cognitive decline. The dementia of PD has a
      grave effect on the quality of life of the patients and their caregivers, as well
      as a negative effect on their survival. The treatment of dementia associated with
      PD with cholinesterase inhibitors produced gratifying (although limited) results.
      Future studies should define the exact role of these agents in the treatment of
      the dementia of PD. Another major problem presented by demented PD patients is
      the occurrence of delusions and hallucinations, which make the life of patients
      and caregivers miserable. Classical neuroleptics are of course contra-indicated
      in these patients but recent data increase concern about the safety of novel
      derivatives, leaving a void in the pharmacological armamentarium available when
      these manifestations appear.

PMID- 17034819
TI  - Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle
      cells via the inhibition of ROS generation and NF-kappaB activation.
AB  - Plantainoside D (PD), was isolated from the leaves of Picrorhiza
      scrophulariiflora (Scrophulariaceae). The anti-oxidative activity of PD was
      evaluated based on scavenging effects on hydroxyl radicals and superoxide anion
      radicals. Adriamycin (ADR) is a potent anti-tumor drug known to cause severe
      cardiotoxicity. Although ADR generates free radicals, the role of free radicals
      in the development of cardiac toxicity has not been understood. This study was
      undertaken to investigate the protective effect of PD against ADR-induced
      apoptosis. In vitro, ADR caused dose-dependent toxicity in H9c2 cardiac muscle
      cells. Pre-treatment of the cardiac muscle cells with PD significantly reduced
      ADR-induced apoptosis of cardiac muscle cells. PD inhibited the ROS produced by
      ADR in the cardiac muscle cells. As well, PD increased GSH(glutathione), compared
      with ADR. In response to ADR, NF-kappaB was activated in H9c2 cells. However the
      treatment of PD reduced the activation of NF-kappaB. We also observed that the NF
      kappaB inhibitor, PDTC, inhibited the cytotoxic effect on ADR-induced apoptosis
      in cardiac muscle cells. In parallel, IkappaBalpha-dominant negative plasmid
      overexpression abrogated ADR-induced apoptosis in H9c2 cardiac muscle cells. In
      conclusion, these results suggest that Plantaionoside D can inhibit ADR-induced
      apoptosis in H9C2 cardiac muscle cells via inhibition of ROS generation and NF
      kappaB activation. The pure compound PD can be a potential candidate agent which
      protects cardiotoxicity in ADR-exposed patients.

PMID- 17034820
TI  - Anthropogenic effects on the smalltooth sawfish (Pristis pectinata) in the United
      States.
AB  - Bycatch mortality in net fisheries was the major reason for the decline of the
      endangered smalltooth sawfish, Pristis pectinata, in the United States. These
      fisheries have been reduced or eliminated in some states including Florida--where
      most smalltooth sawfish are currently found in the United States. To determine
      whether other factors are still affecting this species, we obtained non-net
      fishery entanglement, injury, and mortality data by soliciting information from
      anyone who may have encountered this species. Smalltooth sawfish were damaged by
      marine pollution (e.g., polyvinyl chloride pipe, monofilament line, non
      monofilament line) and injured by humans. Examples of injuries caused directly by
      humans include removal of rostra, shooting an individual with a powerhead, and
      shooting another with arrows. Many people are aware that the smalltooth sawfish
      is protected by state and federal laws, but some are still not aware of (or
      willing to accept) this status. The impacts of marine pollution and injuries
      directly caused by humans on this endangered species can be ameliorated by
      incorporating fisher education into the conservation and management processes.

PMID- 17034821
TI  - Evidence for a dissociation of structural and semantic knowledge in dementia of
      the Alzheimer type (DAT).
AB  - Object recognition and naming deficits in dementia of the Alzheimer type (DAT)
      have typically been attributed to deficits in semantic processing, with only a
      few studies proposing loci of deficits other than semantic. One possible cause of
      DAT object recognition impairments could involve deficits in processing
      structural aspects of visually presented items. In this paper, we assess the
      performance of a group of mild DAT patients on two tasks of structural access,
      object decision, and the complete/incomplete task (based on part-whole matching
      task), as well as on a semantic probes task, designed to assess the patients'
      semantic knowledge of the same items for which structural knowledge had earlier
      been assessed. The DAT patients were substantially impaired in their performance
      on tasks of structural access. Further, no evidence for item-to-item consistency
      in the DAT patients' errors for the structural and semantic tasks was found,
      raising the possibility that structural and semantic knowledge may become
      differentially impaired in DAT.

PMID- 17034824
TI  - Better than a cure.
AB  - A brief glance through the national papers and medical press shows the depth of
      concern with the cost of delivering high quality, free at the point of access
      healthcare to the population. However, at a time of increasingly greater demands
      being placed on public health systems across the globe, the question of how we
      can make health and healthcare both accessible to everyone and sustainable in the
      long term is being posed. In this paper we provide an insight into how England is
      responding to these challenges.

PMID- 17034823
TI  - Assessment of microbiological water quality and its relation to human health in
      Gaza Governorate, Gaza Strip.
AB  - OBJECTIVE: To assess the contamination level of total and faecal coliforms in
      water wells and distribution networks, and their association with human health in
      Gaza Governorate, Gaza Strip. METHODS: Data were obtained from the Palestinian
      Ministry of Health on contamination of total and faecal coliforms in water wells
      and distribution networks, and on the incidence of water-related diseases in Gaza
      Governorate. An interview questionnaire was conducted with 150 residents of Gaza.
      RESULTS: The contamination level of total and faecal coliforms exceeded that of
      the World Health Organization (WHO) limit for water wells and networks. However,
      the contamination percentages in networks were higher than that in wells.
      Giardiasis was strongly correlated with faecal coliform contamination in water
      networks (r=0.7) compared with diarrhoeal diseases and hepatitis A (r=0.3 and
      0.1, respectively). Diarrhoeal diseases were the highest self-reported diseases
      among interviewees in Gaza city. Such diseases were more prevalent among people
      using municipal water than people using desalinated water and water filtered at
      home for drinking (OR=1.6). Intermittent water supply and sewage flooding seemed
      to contribute largely to self-reported diseases. People in Gaza Strip have good
      knowledge on drinking water contamination, and this is reflected in good
      practice. CONCLUSIONS: Water quality has deteriorated in Gaza Strip. This may
      contribute to the prevalence of water-related diseases. Self-reported diseases
      among interviewees in Gaza City were associated with source of drinking water,
      intermittent water supply, sewage flooding and age of water, and wastewater
      networks.

PMID- 17034825
TI  - Purinergic control of the quail rectum: modulation of adenosine 5'-triphosphate
      mediated contraction with acetylcholine.
AB  - Electrical field stimulation (EFS) induces frequency-dependent contractions of
      the longitudinal muscle of isolated quail rectum which were sensitive to
      tetrodotoxin. The aim of the present study was to investigate whether purinergic
      neurons are implicated in the response to nerve stimulation. The shape of the EFS
      induced contractile response was different depending on stimulus frequency; low
      frequencies (0.5-2 Hz) induced fast monophasic contractions with a small
      subsequent relaxation; whereas higher frequencies (5-50 Hz) induced biphasic
      contractile response that comprised fast initial component (as in case of low
      frequency) and a slow delayed contractile component in addition to the relaxation
      that follows the fast contractile component. Prior application of atropine (10
      microM) completely abolished the slow delayed component but significantly
      enhanced the fast initial contractile component. Physostigmine (1-10 microM)
      significantly enhanced the slow delayed component with an inhibitory effect on
      the initial fast component. The nonspecific purinergic receptor antagonist,
      suramin (100-500 microM) significantly inhibited the fast initial contractile
      component with no significant effect on the slow delayed one. Complete blockade
      of the fast component was achieved by prior application of a combination
      consisted of suramin (50 microM) and pyridoxicalphosphate-6-azophenyl 2',4'
      disulphonic acid tetrasodium (PPADS; 10 microM). Exogenous applications of
      adenosine 5'-triphosphate and acetylcholine (10 microM each), produced
      contractile responses that mimicked those induced by EFS. These data suggest that
      ATP is the main noncholinergic excitatory transmitter controlling the contractile
      activity of the quail rectum; and that its action could be modulated by
      acetylcholine.

PMID- 17034826
TI  - An epidermotropic canine papillomavirus with malignant potential contains an E5
      gene and establishes a unique genus.
AB  - A novel canine papillomavirus, CfPV-2, was cloned from a footpad lesion of a
      golden retriever. Unlike the known canine oral papillomavirus (COPV), which has a
      double-stranded DNA genome size of 8607 bps, the genome of CfPV-2 is 8101 bps.
      Some of this size difference is due to an abbreviated early-late region (ELR),
      which is 1200 bps shorter than that of COPV. However, CfPV-2 has other
      differences from COPV, including the presence of an E5 ORF between the E2 gene
      and the ELR and an enlarged E4 ORF (one of the largest PV E4 open reading
      frames). The genome of CfPV-2 shares low homology with all the other
      papillomaviruses and, even in the most highly conserved ORF of L1, the nucleotide
      sequence shares only 57% homology with COPV. Due to this highly divergent DNA
      sequence, CfPV-2 establishes a new PV genus, with its closest phylogenetic
      relatives being amongst the Xi and Gamma genuses. CfPV-2 also has unique
      biological features; it induces papillomas on footpads and interdigital regions
      which, if infection is persistent, can progress to highly metastatic squamous
      cell carcinoma. CfPV-2 does not induce oral papillomas in immunocompetent animals
      and antibodies generated against COPV and CfPV-2 are type-specific. The
      availability of a new canine papillomavirus with differing genetic and biological
      properties now makes it possible to study type-specific host immune responses,
      tissue tropism and the comparative analysis of viral gene functions in the dog.

PMID- 17034827
TI  - Default assembly of early adenovirus chromatin.
AB  - In adenovirus particles, the viral nucleoprotein is organized into a highly
      compacted core structure. Upon delivery to the nucleus, the viral nucleoprotein
      is very likely to be remodeled to a form accessible to the transcription and
      replication machinery. Viral protein VII binds to intra-nuclear viral DNA, as do
      at least two cellular proteins, SET/TAF-Ibeta and pp32, components of a chromatin
      assembly complex that is implicated in template remodeling. We showed previously
      that viral DNA-protein complexes released from infecting particles were sensitive
      to shearing after cross-linking with formaldehyde, presumably after transport of
      the genome into the nucleus. We report here the application of equilibrium
      density gradient centrifugation to the analysis of the fate of these complexes.
      Most of the incoming protein VII was recovered in a form that was not cross
      linked to viral DNA. This release of protein VII, as well as the binding of
      SET/TAF-Ibeta and cellular transcription factors to the viral chromatin, did not
      require de novo viral gene expression. The distinct density profiles of viral DNA
      complexes containing protein VII, compared to those containing SET/TAF-Ibeta or
      transcription factors, were consistent with the notion that the assembly of early
      viral chromatin requires both the association of SET/TAF-1beta and the release of
      protein VII.

PMID- 17034828
TI  - Microplitis demolitor bracovirus genome segments vary in abundance and are
      individually packaged in virions.
AB  - Polydnaviruses (PDVs) are distinguished by their unique association with
      parasitoid wasps and their segmented, double-stranded (ds) DNA genomes that are
      non-equimolar in abundance. Relatively little is actually known, however, about
      genome packaging or segment abundance of these viruses. Here, we conducted
      electron microscopy (EM) and real-time polymerase chain reaction (PCR) studies to
      characterize packaging and segment abundance of Microplitis demolitor bracovirus
      (MdBV). Like other PDVs, MdBV replicates in the ovaries of females where virions
      accumulate to form a suspension called calyx fluid. Wasps then inject a quantity
      of calyx fluid when ovipositing into hosts. The MdBV genome consists of 15
      segments that range from 3.6 (segment A) to 34.3 kb (segment O). EM analysis
      indicated that MdBV virions contain a single nucleocapsid that encapsidates one
      circular DNA of variable size. We developed a semi-quantitative real-time PCR
      assay using SYBR Green I. This assay indicated that five (J, O, H, N and B)
      segments of the MdBV genome accounted for more than 60% of the viral DNAs in
      calyx fluid. Estimates of relative segment abundance using our real-time PCR
      assay were also very similar to DNA size distributions determined from
      micrographs. Analysis of parasitized Pseudoplusia includens larvae indicated that
      copy number of MdBV segments C, B and J varied between hosts but their relative
      abundance within a host was virtually identical to their abundance in calyx
      fluid. Among-tissue assays indicated that each viral segment was most abundant in
      hemocytes and least abundant in salivary glands. However, the relative abundance
      of each segment to one another was similar in all tissues. We also found no clear
      relationship between MdBV segment and transcript abundance in hemocytes and fat
      body.

PMID- 17034829
TI  - Deployment of visual attention before sequences of goal-directed hand movements.
AB  - We examined the allocation of attention during the preparation of sequences of
      manual pointing movements in a dual task paradigm. As the primary task, the
      participants had to perform a sequence of two or three reaching movements to
      targets arranged on a clock face. The secondary task was a 2AFC discrimination
      task in which a discrimination target (digital 'E' or '3') was presented among
      distractors either at one of the movement goals or at any other position. The
      data show that discrimination performance is superior at the location of all
      movement targets while it is close to chance at the positions that were not
      relevant for the movement. Moreover, our findings demonstrate that all movement
      relevant locations are selected in parallel rather than serially in time, and
      that selection involves spatially distinct, non-contiguous foci of visual
      attention. We conclude that during movement preparation--well before the actual
      execution of the hand movement--attention is allocated in parallel to each of the
      individual movement targets.

PMID- 17034830
TI  - Cellular pattern formation during retinal regeneration: a role for homotypic
      control of cell fate acquisition.
AB  - A dominant mechanism of cellular patterning in the growing fish retina is control
      of cell fate acquisition by negative feedback signals arising from differentiated
      cells. We tested the ability of a computational model of this pattern formation
      mechanism to simulate cellular patterns in regenerated goldfish retina. The model
      successfully simulated quantitative features of in vivo regenerated patterns,
      indicating that regenerating retina has access to and utilizes patterning
      mechanisms that are operational during normal growth. The atypical patterns of
      regenerated retina could arise in part from regenerative progenitors that,
      compared to normal growth progenitors, are less responsive to the feedback
      patterning signals.

PMID- 17034831
TI  - The direction aftereffect is driven by adaptation of local motion detectors.
AB  - The processing of motion information by the visual system can be decomposed into
      two general stages; point-by-point local motion extraction, followed by global
      motion extraction through the pooling of the local motion signals. The direction
      aftereffect (DAE) is a well known phenomenon in which prior adaptation to a
      unidirectional moving pattern results in an exaggerated perceived direction
      difference between the adapted direction and a subsequently viewed stimulus
      moving in a different direction. The experiments in this paper sought to identify
      where the adaptation underlying the DAE occurs within the motion processing
      hierarchy. We found that the DAE exhibits interocular transfer, thus
      demonstrating that the underlying adapted neural mechanisms are binocularly
      driven and must, therefore, reside in the visual cortex. The remaining
      experiments measured the speed tuning of the DAE, and used the derived function
      to test a number of local and global models of the phenomenon. Our data provide
      compelling evidence that the DAE is driven by the adaptation of motion-sensitive
      neurons at the local-processing stage of motion encoding. This is in contrast to
      earlier research showing that direction repulsion, which can be viewed as a
      simultaneous presentation counterpart to the DAE, is a global motion process.
      This leads us to conclude that the DAE and direction repulsion reflect
      interactions between motion-sensitive neural mechanisms at different levels of
      the motion-processing hierarchy.

PMID- 17034832
TI  - Exclusion failure does not demonstrate unconscious perception II: evidence from a
      forced-choice exclusion task.
AB  - Systematic failure to perform exclusion (making a response that opposes the
      participant's natural inclinations) for briefly displayed, masked words has been
      interpreted as evidence of unconscious perception. The present study required
      participants to make a forced-choice exclusion after viewing masked word targets.
      The forced-choice exclusion task was properly performed in all experiments, in
      contrast to previous studies that have utilized stem-completion as a dependent
      variable. The exclusion failure effects interpreted as unconscious perception in
      earlier studies appear to be caused by an insensitive dependent variable (stem
      completion) rather than unconscious perception.

PMID- 17034833
TI  - Perceptual filling-in from the edge of the blind spot.
AB  - Looking at the world with one eye, we do not notice a scotoma in the receptor
      free area of the visual field where the optic nerve leaves the eye. Rather we
      perceive the brightness, color, and texture of the adjacent area as if they were
      actually there. The mechanisms underlying this kind of perceptual filling-in
      remain controversial. To better understand these processes, we determined the
      minimum region around the blind spot that needs to be stimulated for filling-in
      by carefully mapping the blind spot and presenting individually fitted stimulus
      frames of different width around it. Uniform filling-in was observed with frame
      widths as narrow as 0.05 degrees visual angle for color and 0.2 degrees for
      texture. Filling-in was incomplete, when the frame was no longer contiguous with
      the blind spot border due to an eye movement. These results are consistent with
      the idea that perceptual filling-in of the blind spot depends on local processes
      generated at the physiological edge of the cortical representation.

PMID- 17034834
TI  - Arsenic in soils and plants of woodland regenerated on an arsenic-contaminated
      substrate: a sustainable natural remediation?
AB  - Plant As accumulation at three As-polluted sites where spontaneous re-vegetation
      has taken place is examined. Each site had a different source of soil As (coal
      fly ash, LeBlanc process waste, canal dredging). Plant analysis indicates that
      soil-plant As transfer is poor at each site. Any mobile As is retained in root
      tissues, with little transfer to shoots. Bryophytes, pteridophytes, herbaceous
      and woody plants sampled at each site predominantly showed As concentrations of
      <3 mg kg(-1) dry wt, whilst total soil As ranged between 50 and 220 mg kg(-1) dry
      wt. Risk associated with food chain transfer at these sites is low when compared
      to other routes such as direct ingestion/inhalation of As-contaminated
      particulates re-entrained from an unvegetated or unstable substrate.

PMID- 17034835
TI  - Evidence of hypercoagulability and inflammation in young patients long after
      acute cerebral ischaemia.
AB  - INTRODUCTION: Young subjects with acute cerebral ischaemia - stroke or transient
      ischaemic attack - form an etiologically heterogeneous and often not clearly
      explained group of patients. The aim was to investigate possible disturbances in
      haemostasis and inflammation long after an acute cerebral ischaemic event.
      MATERIALS AND METHODS: Forty-four consecutive patients referred after having
      suffered from acute cerebral ischaemia before the age of 45 participated 1 to 9
      years (median value 5 years) after the event. At the time of blood sampling 33
      (75%) patients were receiving antithrombotic treatment. Forty-six apparently
      healthy subjects of the same age group served as controls. In all subjects global
      haemostasis parameters (overall haemostasis, coagulation and fibrinolytic
      potential), thrombophilia, several markers of haemostasis activation and
      inflammation were determined. RESULTS: Patients did not differ from controls in
      most of the conventional risk factors and the presence of most forms of
      thrombophilia, although in seven (17.5%) patients the weak presence of lupus
      anticoagulants was observed. Patients had significantly increased overall
      haemostasis and coagulation potential, increased soluble P-selectin and D-dimer,
      decreased overall fibrinolysis potential and increased fibrinogen and C-reactive
      protein compared to controls. The subgroups of patients receiving antiplatelet
      treatment, with thrombophilia and recurrent acute cerebral ischaemia, did not
      differ significantly from the other patients. CONCLUSIONS: In young patients long
      after acute cerebral ischaemia an imbalance in the haemostatic system and a
      minor, but significant degree of inflammation was detected. The mechanisms behind
      haemostatic imbalance seem to be enhanced thrombin generation, platelet
      activation and depressed fibrinolysis.

PMID- 17034836
TI  - Caspase 9 is decreased in psoriatic epidermis.
AB  - Psoriasis is a proliferative and inflammatory disease of the skin. Caspase 9 is
      responsible for initiating the caspase activation cascade during apoptosis.
      Apoptosis is a physiological mechanism of homeostasis and development, and
      caspases are the executioners of apoptosis. This study reports the
      immunohistochemical localisation of caspase 9 in psoriatic skin and compares it
      with that seen in normal, healthy control skin. Skin biopsy specimens of lesions
      were obtained from 15 patients with plaque type psoriasis vulgaris. The specimens
      were labelled immunohistochemically for binding of an anti-caspase 9 primary
      antibody. Biopsies of healthy skin from 10 age-matched and sex-matched healthy
      control individuals were also analysed. The caspase 9 positive cell fraction was
      calculated for both epidermal and dermal cells in psoriatic lesions and healthy
      control skin. Counts of caspase 9 positive cells from the epidermis of psoriatic
      skin lesions were significantly lower than those seen in healthy skin (p<0.05).
      The caspase 9 immunolabelled perivascular cell counts in the dermis were not
      statistically significantly different in psoriatic lesions versus normal skin
      (p>0.05). Psoriatic epidermis contains little of the apoptotic marker, caspase 9.
      The results of this study are indicative of decreased apoptosis in psoriatic
      epidermis, and no change in the perivascular area in psoriatic lesions. These
      findings support the idea that decreased apoptosis is seen in psoriatic epidermal
      cells. Greater understanding of the nature of the disease may open new avenues
      for further therapeutic modalities.

PMID- 17034837
TI  - Synchronous ovarian granulosa cell tumor and uterine serous carcinoma: a rare
      association of a high-risk endometrial cancer with anestrogenic ovarian tumor.
AB  - BACKGROUND: Ovarian granulosa cell tumors are often associated with endometrial
      hyperplasia or carcinoma. The endometrial carcinoma is thought to occur under the
      influence of the estrogen receptor pathway and is typically a low-grade, low
      stage endometrioid adenocarcinoma. CASE: We present a case of a woman with a
      granulosa cell tumor of the ovary and a synchronous serous carcinoma of the
      endometrium. Immunohistochemical stains for estrogen receptors, progesterone
      receptors, and p53 protein were performed on both tumors. CONCLUSIONS: Not all
      uterine tumors associated with ovarian granulosa cell tumors have low-risk
      histology. Preoperative evaluation of the uterus with attention to tumor
      subtyping is important for optimum staging and therapy.

PMID- 17034838
TI  - Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial
      ovarian cancer.
AB  - OBJECTIVE: We investigated the expression of matrix metalloproteinase-9 (MMP-9)
      and its relation to clinicopathologic factors and survival and also to previously
      analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer.
      METHODS: The expression of MMP-9 was analyzed immunohistochemically in 292
      primary tumors and their 31 metastases. RESULTS: A low proportion of strong MMP-9
      expression in cancer cells and high stromal MMP-9 expression correlated with
      advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9
      expression significantly correlated with hyaluronan positivity (p<0.0005),
      whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10
      year disease-related survival (DRS) was found in patients with a high proportion
      of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05,
      respectively). However, high stromal expression of MMP-9 indicated short DRS
      (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or
      stromal cells were not independent prognostic factors, while in FIGO stage I
      patients a high percentage of MMP-9 positive cancer cells was associated with
      long DRS (p=0.008). CONCLUSION: These data suggest that MMP-9 has a dual role in
      tumor progression, acting against tumor advancement when in tumor epithelium and
      promoting tumor progression while in the stroma.

PMID- 17034839
TI  - Relevant molecular markers and targets.
AB  - Ovarian cancer is a heterogeneous disease with extensive cytogenetic and
      molecular heterogeneity including aneuploidy, chromosomal alterations, mutations
      and overexpression as well as a natural propensity to disseminate and spread,
      making it difficult to diagnose at an early stage. Insights into the molecular
      mechanisms operative in cancer development, progression and metastasis have
      uncovered a wide array of targets for therapeutic intervention. In the absence of
      a common driving oncogene in ovarian cancer, single targeted therapy for this
      disease is unlikely to yield significant clinical benefit. Tailored approaches
      that combine molecular targeting agents with cytotoxic regimens hold great
      promise when used in primary treatment, during consolidation and maintenance
      therapy, and in the treatment of persistent or recurrent disease. The most
      promising treatment strategies are those that target the drivers of tumorigenesis
      and enhance the activity of cytotoxic agents. Receptor tyrosine kinases, non
      receptor tyrosine kinases, serine/threonine kinases, transferases, proteases and
      deacetylases are among the relevant molecular markers and targets for ovarian
      cancer that are discussed. Collaboration, coordination, creativity and aggressive
      outreach to patients and their advocates are essential for success in running the
      concurrent trials with multiple clinical end points and embedded translational
      research that are needed to evaluate the array of promising targeted therapeutics
      and combinations. Validated biomarkers, surrogate specimens and end points, and
      additional clinically relevant in vitro and in vivo models for ovarian cancer are
      needed to facilitate the drug development and evaluation process, and ultimately
      to make meaningful improvements in the diagnosis, prevention and management of
      ovarian cancer.

PMID- 17034840
TI  - The effects of chronic valproate and diazepam in a mouse model of posttraumatic
      stress disorder.
AB  - To better understand neurochemical and psychopharmacological aspects of post
      traumatic stress disorder (PTSD), it is necessary establish an animal model of
      PTSD in which behavioral changes persist for a long time after the initial
      traumatization. The present study aimed to characterize long-term behavioral
      alterations in male ICR mice as an animal model of PTSD consisting of a 2-day
      foot shock (0.8 mA, 10 s) followed by 3 weekly situational reminders (SR), and to
      evaluate the effects of repeated administration of valproate and diazepam on
      behavioral deficits of this animal model. The results showed that the aversive
      procedure induced several long-term behavioral deficiencies: increased freezing
      behavior and anxiety level, reduced time spent in an aversive like context.
      Repeated treatment with valproate (100-400 mg/kg, i.p.) induced a dose-dependent
      reduction of these behavioral changes. In contrast, diazepam at a low dose (0.25
      mg/kg) but not at a high dose (4 mg/kg) reduced the behavioral deficiencies.
      These results demonstrate that exposure to intense foot shock associated with
      repeated situational reminders elicits long-term disturbances that last about 4
      weeks after the foot shock exposure. These behavioral deficits can be ameliorated
      by repeated administration of valproate or diazepam at some special dose ranges.

PMID- 17034841
TI  - Effect of sperm numbers and concentration on sperm transport and uterine
      inflammatory response in the mare.
AB  - Our objective was to determine whether the concentration of cooled sperm
      inseminated influenced sperm transport and intensity of the uterine inflammatory
      reaction 2, 4 and 24h after insemination. Experimental subjects were 189 estrous
      mares with a dominant follicle > or =35 mm in diameter and no bacterial growth or
      neutrophils detected in uterine smears. Each mare was randomly assigned to
      receive one of the following intrauterine treatments (volume, 20 mL):
      insemination with 5x10(6) mL(-1) or 25x10(6) mL(-1) or 50x10(6) mL(-1) sperm
      diluted in 3 mL seminal plasma (SP) and 17 mL skim milk; seminal plasma or skim
      milk extender. Mares in a control group received no intrauterine treatment. Mares
      were slaughtered 2, 4 or 24h after insemination or infusion. Oviducts were
      separated from the uterus, and uterus and oviducts were then flushed with
      phosphate-buffered saline (PBS). After flushing, an endometrial sample was
      collected for further histopathological examination. The grade of uterine
      fibrosis and the amount of neutrophils in the stratum compactum were evaluated. A
      sample of each tubal flushing was examined for sperm count, and a sample of each
      uterine flushing was examined for PMN count. It was concluded that compounds in
      the insemination dose provoked a uterine inflammatory response, which was more
      rapid and intense as sperm concentration increased. In contrast, sperm transport
      through 4h after insemination was not influenced by sperm concentration.

PMID- 17034842
TI  - Birth of offspring of pre-determined sex after artificial insemination of frozen
      thawed, sex-sorted and re-frozen-thawed ram spermatozoa.
AB  - The fertility of ram spermatozoa cryopreserved prior to, and following, sex
      sorting by flow cytometry was assessed after insemination of mature Merino ewes
      at a synchronised estrus. Ewes were inseminated with spermatozoa from three rams,
      split into four treatment groups: 50 x 10(6) motile non-sorted, frozen-thawed
      (Control50), 15 x 10(6) motile non-sorted, frozen-thawed (Control15), 15 x 10(6)
      motile sex-sorted, frozen-thawed (SF15) or 15 x 10(6) motile frozen-thawed, sex
      sorted, re-frozen-thawed (FSF15) ram spermatozoa. Separation of SF15 and FSF15
      treatments into X- and Y-chromosome-bearing populations was achieved using a high
      speed sperm sorter. The percentage of ewes lambing after insemination was similar
      for Control15 (36/74; 48.6%), SF15 (35/76; 46.1%) and FSF15 (26/72; 36.1%) groups
      (P>0.05). A higher percentage of ewes produced lambs in the Control50 (38/70;
      54.3%) than the FSF15 group (P<0.05). Fifty-one of the 55 (92.7%) lambs derived
      from fresh, sex-sorted frozen-thawed spermatozoa were of the predicted sex, as
      were 41/43 (95.3%) lambs derived from frozen-thawed, sex-sorted, re-frozen-thawed
      spermatozoa. This study demonstrated for the first time in any species that
      frozen-thawed spermatozoa, after sex-sorting and a second cryopreservation step,
      are capable of producing offspring of the predicted sex following artificial
      insemination.

PMID- 17034843
TI  - Relationships among predatory fish, sea urchins and barrens in Mediterranean
      rocky reefs across a latitudinal gradient.
AB  - Previous studies conducted on a local scale emphasised the potential of trophic
      cascades in Mediterranean rocky reefs (involving predatory fish, sea urchins and
      macroalgae) in affecting the transition between benthic communities dominated by
      erected macroalgae and barrens (i.e., bare rock with partial cover of encrusting
      algae). Distribution patterns of fish predators of sea urchins (Diplodus sargus
      sargus, Diplodus vulgaris, Coris julis and Thalassoma pavo), sea urchins
      (Paracentrotus lividus and Arbacia lixula) and barrens, and fish predation rates
      upon sea urchins, were assessed in shallow (3-6m depth) sublittoral rocky reefs
      in the northern, central and southern sectors of the eastern Adriatic Sea, i.e.,
      on a large spatial scale of hundreds of kilometres. No dramatic differences were
      observed in predatory fish density across latitude, except for a lower density of
      small D. sargus sargus in the northern Adriatic and an increasing density of T.
      pavo from north to south. P. lividus did not show any significant difference
      across latitude, whereas A. lixula was more abundant in the southern than in the
      central Adriatic. Barrens were more extended in the southern than in the central
      and northern sectors, and were related with sea urchin density. Fish predation
      upon adult sea urchins did not change on a large scale, whereas it was slightly
      higher in the southern sector for juveniles when predation rates of both urchins
      were pooled. Results show that: (1) assemblages of predatory fish and sea
      urchins, and barren extent change across latitude in the eastern Adriatic Sea,
      (2) the weak relations between predatory fish density and predation rates on
      urchins reveal that factors other than top-down control can be important over
      large scale (with the caveat that the study was conducted in fished areas) and
      (3) patterns of interaction among strongly interacting taxa could change on large
      spatial scales and the number of species involved.

PMID- 17034844
TI  - A biodegradable poly(ester amine) based on polycaprolactone and polyethylenimine
      as a gene carrier.
AB  - The aim of research was to develop and optimize delivery systems for plasmid DNA
      (pDNA) based on biodegradable polymers, in particular, poly(ester amine)s (PEAs),
      suitable for non-viral gene therapy. Poly(ester amine)s were successfully
      synthesized by Michael addition reaction between polycaprolactone (PCL)
      diacrylate and low molecular weight polyethylenimine (PEI). PEA/DNA complexes
      showed effective and stable DNA condensation with the particle sizes below 200nm,
      implicating its potential for intracellular delivery. PEAs showed controlled
      degradation and were essentially non-toxic in all three cells (293T: Human kidney
      carcinoma, HepG2: Human hepatoblastoma and HeLa: Human cervix epithelial
      carcinoma cell lines) at higher doses in contrast to PEI 25K. PEAs also revealed
      much higher transfection efficiencies in three cell lines as compared to PEI 25K.
      The highest reporter gene expression was observed for PCL/PEI-1.2 (MW 1200)
      complex having transfection efficiency 15-25 folds higher than PEI 25K in vitro.
      Also PEA/DNA complexes successfully transfected cells in vivo after aerosol
      administration than PEI 25K. These PEAs can be used as most efficient polymeric
      vectors which provide a versatile platform for further investigation of structure
      property relationship along with the controlled degradation, significant low
      cytotoxicity and high transfection efficiency.

PMID- 17034845
TI  - In vitro fatigue-crack growth and fracture toughness behavior of thin-walled
      superelastic Nitinol tube for endovascular stents: A basis for defining the
      effect of crack-like defects.
AB  - Endovascular stents made of the superelastic nickel-titanium alloy Nitinol are
      subjected in service to tens of millions of loading cycles and even "single
      event" overloads, both of which can potentially result in fracture and/or
      complete failure of the device. A fracture-mechanics-based methodology can
      provide a means to quantify relevant material parameters critical to the design
      against such failures. However, there is a dearth of relevant experimental data
      in the literature on such fracture-mechanics-based approaches to fatigue in
      Nitinol; furthermore, that which does exist invariably pertains to product forms
      that are not appropriate for stent manufacture, e.g., bulk Nitinol bar and strip.
      Consequently, the current work is focused on characterizing in vitro both
      subcritical and critical crack growth (fatigue-crack growth and R-curve fracture
      toughness) behavior in thin-walled ( approximately 400microm thick) Nitinol
      tubing similar to that used for medical device manufacture (following shape
      setting procedures to flatten the material), with a resultant austenite finish
      temperature of A(f) approximately 25-30 degrees C, identical to self-expanding
      Nitinol stents. Fatigue-crack growth behavior, measured in Hanks' Balanced Saline
      Solution over a wide spectrum of growth rates (down to 10(-10)m/cycle) and at a
      range of positive load ratios (R=0.1-0.7), revealed significantly higher fatigue
      thresholds than had been previously reported for bulk Nitinol material. In
      addition, we examine the critical effect of test frequency, as most fatigue
      experiments on Nitinol have been performed at 30Hz or above, despite the fact
      that this is far in excess of the frequency of physiological loading. Finally,
      the fracture toughness properties are characterized in thin-section Nitinol and
      show marked crack-resistance (R-curve) behavior with a dependence on crack-growth
      angle (with respect to the tube drawing axis); additionally, measured toughnesses
      are found to be lower than has been previously reported for bulk Nitinol.

PMID- 17034846
TI  - Engineered matrix coatings to modulate the adhesion of CD133+ human hematopoietic
      progenitor cells.
AB  - Interactions of hematopoietic progenitor cells (HPC) with their local
      microenvironments in the bone marrow are thought to control homing,
      differentiation, and self-renewal of the cells. To dissect the role of
      extracellular matrix (ECM) components of the niche microenvironment, a set of
      well-defined ECM coatings including fibronectin, heparin, heparan sulphate,
      hyaluronic acid, tropocollagen I, and co-fibrils of collagen I with heparin or
      hyaluronic acid was prepared and analysed with respect to the attachment of human
      CD133+ HPC in vitro. The extension of the adhesion areas of individual cells as
      well as the fraction of adherent cells were assessed by reflection interference
      contrast microscopy (RICM). Intense cell-matrix interactions were found on
      surfaces coated with fibronectin, heparin, heparan sulphate, and on the collagen
      I based co-fibrils. Insignificant adhesion was found for tropocollagen I and
      hyaluronic acid. The strongest adhesion of HPC was observed on fibronectin with
      contact areas of about 7 microm(2). Interaction of HPC with coatings consisting
      of heparin, heparan sulphate, and co-fibrils result in small circular shaped
      contact zones of 3 microm(2) pointing to another, less efficient, adhesion
      mechanism. Analysing the specificity of cell-matrix interaction by antibody
      blocking experiments suggests an integrin(alpha(5)beta(1))-specific adhesion on
      fibronectin, while adhesion on heparin was shown to be mediated by selectins
      (CD62L). Taken together, our data provide a basis for the design of advanced
      culture carriers supporting site-specific proliferation or differentiation of
      HPC.

PMID- 17034847
TI  - The effect of gradually graded shear stress on the morphological integrity of a
      huvec-seeded compliant small-diameter vascular graft.
AB  - The premature endothelialization of tissue-engineered grafts had often induced
      cellular detachment at an early period of implantation in arterial circulation,
      resulting in occlusion at an early period of implantation. This study was aimed
      to determine whether gradually increased shear stress applied ex vivo improves
      cell retention and tissue morphological integrity including cell shape and
      alignment, actin fiber alignment and expression of vascular endothelial (VE)
      cadherin. Tissue-engineered grafts used for this study were human umbilical vein
      endothelial cell (HUVEC)-seeded compliant small-diameter grafts made of poly(L
      lactide-co-epsilon-caprolactone) fiber meshes fabricated by electrospinning. The
      shear stresses applied to grafts, generated using a custom-designed mock
      circulatory apparatus, were 3.2, 8.7 and 19.6 dyn/cm(2). The grafts completely
      monolayered prior to shear stress exposure exhibited a polygonal cobblestone
      morphology with randomly distributed actin fibers and VE cadherin at the
      continuous peripheral region of adjacent cells. The 24-h-loading of high shear
      stresses (8.7 and 19.6 dyn/cm(2)) equivalent to those of the arterial circulatory
      system resulted in severe cellular damage resulting in the complete loss of
      cells. However, a gradually increased graded exposure from a low (3.2 dyn/cm(2))
      to a high shear stress (19.6 dyn/cm(2)) resulted in a markedly reduced cell
      detachment, a highly elongated cell shape, and orientation or alignment of both
      cells and actin fibers, which were parallel to the direction of flow. Although VE
      cadherin expression was not detected yet, a higher degree of tissue integrity was
      achieved, which may greatly improve the performance particularly at an early
      period of implantation.

PMID- 17034848
TI  - Absolute quantification of gene expression in biomaterials research using real
      time PCR.
AB  - One major measurement of tissue-engineered constructs efficacy and performance is
      determining expression levels of genes of interest at the molecular level. This
      measurement is commonly carried out with reverse transcription-polymerase chain
      reaction (RT-PCR). In this study, we described a novel method in achieving
      absolute quantification of gene expression using real-time PCR (aqPCR). This
      novel method did not require molecular cloning steps to prepare the standards for
      quantification comparison. Standards were linear double-stranded DNA molecules
      instead of the typical gene-in-plasmid format. aqPCR could also be used to give
      relative quantification comparisons between samples simply by dividing the copy
      numbers readings of the gene of interest with that of the normalization gene. RNA
      was extracted from monolayer and from polycaprolactone scaffold cultures and
      assayed for beta-actin and osteocalcin genes. We compared our aqPCR method with
      end-point PCR since end-point PCR is still a common means of measuring gene
      expression in the biomaterials field. This study showed that aqPCR was a better
      method to quantify gene expression than end-point PCR. With our described linear
      DNA standards method, we were able to obtain not only relative quantification of
      osteocalcin and beta-actin expression level but also actual copy numbers of
      osteocalcin and beta-actin for the monolayer culture and to be 1.34 x 10(4) and
      1.45 x 10(7) copies, respectively and for the scaffold cultures to be 772 and
      2.83 x 10(5) copies, respectively per starting total RNA mass of 10 ng. The
      standards curves made from these linear DNA standards showed good linearity
      (R(2)=0.9964 and 0.9902 for osteocalcin and beta-actin standards graphs), ranged
      from 10 to 10(9) copies and of comparable accuracy to current absolute
      quantification real-time PCR methods (which used plasmid standards obtained
      through molecular cloning methods). Our method might be a viable and more user
      friendly alternative to current absolute quantification real-time PCR protocols.

PMID- 17034849
TI  - Calcium signaling complexes in microdomains of polarized secretory cells.
AB  - The highly polarized nature of epithelial cells in exocrine glands necessitates
      targeting, assembly into complexes and confinement of the molecules comprising
      the Ca(2+) signaling apparatus, to cellular microdomains. Such high degree of
      polarized localization has been shown for all Ca(2+) signaling molecules tested,
      including G protein coupled receptors and their associated proteins, Ca(2+)
      pumps, Ca(2+) influx channels at the plasma membrane and Ca(2+) release channels
      in the endoplasmic reticulum. Although the physiological significance of
      polarized Ca(2+) signaling is clear, little is known about the mechanism of
      targeting, assembly and retention of Ca(2+) signaling complexes in cellular
      microdomains. The present review attempts to summarize the evidence in favor of
      polarized expression of Ca(2+) signaling proteins at the apical pole of secretory
      cells with emphasis on the role of scaffolding proteins in the assembly and
      function of the Ca(2+) signaling complexes. The consequence of polarized
      enrichment of Ca(2+) signaling complexes at the apical pole is generation of an
      apical to basal pole gradient of cell responsiveness that, at low physiological
      agonist concentrations, limits Ca(2+) spikes to the apical pole, and when a
      Ca(2+) wave occurs, it always propagates from the apical to the basal pole. Our
      understanding of Ca(2+) signaling in microdomains is likely to increase rapidly
      with the application of techniques to controllably and selectively disrupt
      components of the complexes and apply high resolution recording techniques, such
      as TIRF microscopy to this problem.

PMID- 17034850
TI  - Calcium microdomains and gene expression in neurons and skeletal muscle cells.
AB  - Neurons generate particular calcium microdomains in response to different
      stimuli. Calcium microdomains have a central role in a variety of neuronal
      functions. In particular, calcium microdomains participate in long-lasting
      synaptic plasticity--a neuronal response presumably correlated with cognitive
      brain functions that requires expression of new gene products. Stimulation of
      skeletal muscle generates - with few milliseconds delay - calcium microdomains
      that have a central role in the ensuing muscle contraction. In addition, recent
      evidence indicates that sustained stimulation of skeletal muscle cells in culture
      generates calcium microdomains, which stimulate gene expression but not muscle
      contraction. The mechanisms whereby calcium microdomains activate signaling
      cascades that lead to the transcription of genes known to participate in specific
      cellular responses are the central topic of this review. Thus, we will discuss
      here the signaling pathways and molecular mechanisms, which via activation of
      particular calcium-dependent transcription factors regulate the expression of
      specific genes or set of genes in neurons or skeletal muscle cells.

PMID- 17034851
TI  - Vector-based RNAi approach to isoform-specific downregulation of vascular
      endothelial growth factor (VEGF)165 expression in human leukemia cells.
AB  - Vascular endothelial growth factor (VEGF) plays a critical role during normal
      embryonic angiogenesis and also in the pathological angiogenesis that occurs in a
      number of diseases, including cancer. K562 human leukemia cells overexpress VEGF,
      with a shift in isoform production from membrane-bound VEGF189 to the more
      soluble VEGF165. In the present study, three 19 bp reverse repeated motifs
      targeting exons 5 and 7 boundary of VEGF165 gene sequence with 9 bp spacer were
      synthesized and cloned into eukaryotic expression plasmid pGenesil-1 containing
      U6 shRNA promoter and termination signal of RNA polymerase. The recombinant
      plasmids pGenesil-VR1, pGenesil-VR2, pGenesil-VR3 and pGenesil-con (plasmid
      containing random DNA fragment) were transfected into K562 cells, respectively,
      through lipofectamine reagent. A vector-based small interfering RNA(SiRNA)
      inhibited VEGF165 mRNA expression by 72% and protein production by 67% in K562
      cells. Human microvascular endothelial cell migration induced by conditioned
      medium from VEGFsi-transfected K562 cells was significantly less than that
      induced by conditioned medium from K562 cells and control vector-transfected K562
      cells. Furthermore, the VEGF shRNA dramatically suppressed tumor angiogenesis and
      tumor growth in a K562 s.c. xenograft model. Vessel density as assessed by vWF
      immunohistochemical analysis was also decreased. This strategy provides a novel
      tool to study the function of various VEGF isoforms and may contribute to VEGF
      specific treatment in cancer.

PMID- 17034852
TI  - [Evaluation of a group intervention using a feminist approach for women
      experiencing sexual abuse].
AB  - OBJECTIVE: The present study evaluates a group intervention using a feminist
      approach for women experiencing sexual abuse in childhood or adulthood in order
      to measure changes associated with participation in a group intervention and
      verifies whether effects are maintained over time. The present study relates
      effects of the group intervention in terms of psychological distress, depression
      symptoms, post-traumatic stress symptoms and feelings of guilt and helplessness.
      METHOD: The sample consists of 26 women participating in a group intervention
      offered by sexual assault centers in Quebec (CALACS - Centre d'aide et de lutte
      contre les agressions a caractere sexuel). RESULTS: Results show significant
      differences between pretest and post-test scores obtained one week following the
      end of the group intervention and gains are maintained at follow-up 3 months
      later. CONCLUSION: The findings suggest that participation in the group
      intervention is associated with a reduction of psychological distress, depression
      symptoms, post-traumatic stress symptoms and feelings of guilt and helplessness
      in adult women reporting sexual abuse.

PMID- 17034853
TI  - Real-time gene expression analysis in carp (Cyprinus carpio L.) skin:
      inflammatory responses to injury mimicking infection with ectoparasites.
AB  - We studied a predictive model of gene expression induced by mechanical injury of
      fish skin, to resolve the confounding effects on the immune system induced by
      injury and skin parasite-specific molecules. We applied real time quantitative
      PCR (RQ-PCR) to measure the expression of the pro-inflammatory cytokines CXCa,
      CXCb, interleukin (IL)1-beta, tumor necrosis factor alpha (TNFalpha), and the
      receptors IL1R1, CXCR1 and CXCR2 in skin of Cyprinus carpio after mechanical
      injury. We also studied the expression of the anti-inflammatory cytokine IL-10.
      Most obvious, specific up-regulation of the chemokine CXCa, the chemokine
      receptor CXCR1 and the pro-inflammatory cytokine IL-beta was detected at 2-3h
      after injury. In order to correlate gene expression patterns after injury with
      cell migration, we studied chemotaxis of head kidney leukocytes towards lysates
      of epithelioma papulosum cyprini (EPC) cells. Neutrophilic granulocytes were
      shown to migrate towards epithelial lysates. Using immunohistochemistry we
      observed that the early inflammatory response after injury involved an influx of
      cells, most probably neutrophilic granulocytes, into the injured area. This
      suggests that the increased expression of pro-inflammatory genes is related to a
      rapid influx of neutrophilic granulocytes.

PMID- 17034854
TI  - Lipophilicity parameters for ionic liquid cations and their correlation to in
      vitro cytotoxicity.
AB  - Regarding the great structural variability of the currently expanding group of
      ionic liquids, it is highly desirable to understand the basic factors affecting
      their toxicity in different biological systems. The present study of a set of 74
      ionic liquids with imidazolium, pyrrolidinium, pyridinium, quinolinium,
      quaternary phosphonium and quaternary ammonium cations and the comparatively
      small anions Cl(-), Br(-), BF(4)(-), or PF(6)(-) demonstrates the influence of
      the cation lipophilicity on the cytotoxicity in IPC-81 leukemia cells from rats.
      The scope of this correlation is limited to ionic liquids with these or similarly
      small anions that are sufficiently nonreactive under physiological and
      chromatographic conditions and whose cation lipophilicity does not exceed a
      certain threshold.

PMID- 17034855
TI  - Occurrence of Bifidobacterium in the intestine of newborns by fluorescence in
      situ hybridization.
AB  - Colonization by Bifidobacterium occurs generally within 4 days of life. The new
      method FISH has been applied for molecular detection of Bifidobacteria. The study
      was carried out on 26 healthy newborns delivered by vaginal delivery. Breast-fed
      infants harbor a gastrointestinal flora characterized by an increased
      concentration of Bifidobacterium cells (by a factor of 1.75). In artificial
      alimentation, some infants either did not harbor any Bifidobacterium or showed
      lower numbers of Bifidobacterium. Moreover, male newborns show higher numbers of
      Bifidobacterium, but in both sexes the predominance of Bifidobacterium is evident
      after maternal alimentation.

PMID- 17034856
TI  - Seroepidemiological survey of Rhodoccocus equi infection in asymptomatic horses
      from Bursa, Izmir and Istanbul provinces, Turkey.
AB  - In order to assess the Rhodococcus equi infection in three provinces of Turkey
      (Bursa, Izmir and Istanbul), 696 sera from healthy foals and adult horses were
      tested by indirect ELISA using a R. equi reference strain (ATCC 6939) as antigen.
      103 sera (14.80%) with titres >0.646 resulted positive. Seroprevalence was
      significantly higher (P=0.0053) in male than in female horses of Istanbul
      province, although higher antibody titres (mean value) were observed in the
      female group of Bursa and Izmir provinces with differences estimated between
      provinces (P=0.0002). Seroprevalence was correlated with age: foals aged less
      than 1 year (P<10(-4)) and horses from 5 to 10 years old (P=0.018) resulted more
      infected in Bursa and Izmir provinces. Our findings indicate that R. equi
      infection actually occurs in all investigated provinces, suggesting the
      importance of serological survey to diagnose the infection and to prevent the
      zoonotic risk.

PMID- 17034857
TI  - Immune modulation by probiotic strains: quantification of phagocytosis of
      Aeromonas salmonicida by leukocytes isolated from gut of rainbow trout
      (Oncorhynchus mykiss) using a radiolabelling assay.
AB  - A method is described for the rapid and sensitive assay of phagocytosis that
      utilizes radioactively labelled bacteria. With this method, we observed that
      phagocytosis of heat-inactivated Aeromonas salmonicida by leukocytes isolated
      from gut of rainbow trout fed with different viable probiotics (Lactococcus
      lactis subsp. lactis, Lactobacillus sakei, and Leuconostoc mesenteroides) was
      significantly higher (P<0.05) after 2 weeks of probiotic-feeding than the control
      group. However, only phagocytosis of live A. salmonicida by the leukocytes
      isolated from gut of rainbow trout fed with L. lactis subsp. lactis was
      significantly higher (P<0.05) than the control group.

PMID- 17034858
TI  - Histological studies on the ontogeny of bovine palatine and pharyngeal tonsil:
      germinal center formation, IgG, and IgA mRNA expression.
AB  - The development and distribution of lymphocyte subsets in calf palatine and
      pharyngeal tonsil were examined. During prenatal development, B cells were
      distributed in the subepithelial area, and T cells and MHC class II(+) cells were
      found in the deep layer of B-cell area, respectively, in both tonsils. At
      neonatal stage, lymphoid follicle containing a few CD4(+) cells have been formed
      in both tonsils. IgG(+) and IgA(+) cells were found in the parafollicular and
      epithelial area. At 3 months old, many germinal centers were recognized in both
      tonsils. CD4(+) cells and IgG mRNA expression were detected in light zone of
      germinal centers. Many IgG, and IgA mRNA expressions also could be detected in
      the parafollicular and subepithelial area of both tonsils. The data suggest that
      both tonsils have an important role of local immune defense against invading
      antigen after birth. The comparison of the histological characteristics of tonsil
      and Peyer's patch during ontogeny is also discussed.

PMID- 17034859
TI  - Porcine interleukin-2 gene encapsulated in chitosan nanoparticles enhances immune
      response of mice to piglet paratyphoid vaccine.
AB  - Interleukin-2 (IL-2) is vital to elicit and amplify the cellular and humoral
      immune responses to foreign antigens, which is extensively utilized in the
      control of infectious disease and treatment of various cancers. Porcine and
      murine IL-2 genes were, respectively, subcloned into VR1020, designated as VPIL-2
      and VMIL-2, and then encapsulated in chitosan nanoparticles (CNP) prepared by
      ionic linkage. The BALB/c mice were intramuscularly co-administrated with
      chitosan-IL-2 nanoparticles (CNP-IL2) and paratyphoid vaccine to test the
      adjuvant effect of CNP-IL2. On day 35, the immunized mice were orally challenged
      with virulent Salmonella. The content of IgG, IgA, IgM, IL-2, IL-4, IL-6 and
      specific antibody titer as well as the number of immunocompetent cells were
      systematically analyzed in the vaccinated mice. The results revealed that the
      levels of immunoglobulins, cytokines, the specific antibodies, together with the
      numbers of lymphocytes significantly increased in vaccinated mice inoculated with
      CNP-VPIL2 in contrast with those with naked IL-2 plasmids and blank plasmids. The
      CNP-VPIL2 immunized mice exhibited higher humoral and cellular immune responses,
      less severe clinical signs and lesions of disease caused by the bacteria than the
      other groups after challenge. These findings suggest that CNP-VPIL2 has a
      significant enhancement effect on immune responses of mice, which results in
      better immunoprotection against Salmonella infection, indicating that CNP-VPIL2
      could be employed as an effective immunoadjuvant to elevate immunity of animals
      to conventional vaccines.

PMID- 17034860
TI  - Isolation of pathogenic Listeria monocytogenes in faeces of wild animals in
      captivity.
AB  - The isolation of pathogenic Listeria spp. in faecal samples of captive wild
      animals was studied. Isolation of the pathogen was attempted from the samples by
      selective enrichment in University of Vermont Medium and plating onto Dominguez
      Rodriguez isolation agar, PALCAM agar and modified McBride Listeria agar.
      Pathogenicity of the isolates was tested by Christie, Atkins, Munch Petersen
      test, phosphotidylinositol-specific phospholipase C assay, mice inoculation test
      and chick embryo bioassay. Listeria monocytogenes was isolated from eight (16%)
      of 50 faecal samples from six different mammals and one bird. Out of eight
      isolates, one isolate from jackal proved to be pathogenic by all the
      pathogenicity testing assays. PCR amplification of virulence genes suggested that
      the isolate was potentially pathogenic.

PMID- 17034861
TI  - Effect of soil properties on arsenic fractionation and bioaccessibility in cattle
      and sheep dipping vat sites.
AB  - Historical use of high arsenic (As) concentrations in cattle/sheep dipping vat
      sites to treat ticks has resulted in severe contamination of soil and groundwater
      with this Group-A human carcinogen. In the absence of a universally applicable
      soil As bioaccessibility model, baseline risk assessment studies have
      traditionally used the extremely conservative estimate of 100% soil As
      bioaccessibility. Several in-vitro, as well as, in-vivo animal studies suggest
      that As bioaccessibility in soil can be lower than that in water. Arsenic in
      soils exists in several geochemical forms with varying degree of dissolution in
      the human digestive system, and thus, with highly varying As bioaccessibility.
      Earlier batch incubation studies with As-spiked soils have shown that As
      bioaccessibility is a function of soil physicochemical properties. We selected 12
      dipping vat soils collected from USA and Australia to test the hypothesis that
      soil properties exert a significant effect on As bioaccessibility in As
      contaminated sites. The 12 soils varied widely in terms of soil physico-chemical
      properties. They were subject to an As sequential fractionation scheme and two in
      vitro tests (IVGS and IVGIA) to simulate soil As bioavailability in the human
      gastrointestinal system. Sequential As fractionation results showed that the
      majority of the As measured in the dipping vat soils resided either in the Fe/Al
      hydroxide fraction, or the Ca/Mg fractions, or in the residual fraction. Water
      extractable As fraction of the 12 soils was typically <10% of the total, reaching
      values up to 23%, indicating minimal leaching potential, and hence, lower risk of
      As-contamination from exposure to groundwater, typically used as drinking water
      in many parts of the world. Partial individual correlations and subsequent
      multiple regression analyses suggested that the most significant soil factors
      influencing As bioaccessibility were total Ca+Mg, total P, clay content and EC.
      Collectively, these soil properties were able to explain 85 and 86% of the
      variability associated with the prediction of bioaccessible As, using IVGS and
      IVGIA in-vitro tests, respectively. This study showed that specific soil
      properties influenced the magnitude of soil As bioaccessibility, which was
      typically much lower than total soil-As concentrations, challenging the
      traditional risk assessment guideline, which assumes that soil As is 100%
      bioaccessible. Our study showed that total soil As concentration is unlikely to
      provide an accurate estimate of human health risk from exposure to dipping vat
      site soils.

PMID- 17034862
TI  - Induction of interferon-gamma by Taenia crassiceps glycans and Lewis sugars in
      naive BALB/c spleen and peritoneal exudate cells.
AB  - Helminth parasites are known to alter host immune responses and the responsible
      molecules are a potential source of biological immunoadjuvants. Previously, we
      have reported strong Th-2 type immunomodulatory properties of Taenia crassiceps
      glycans. In this study, we report interferon-gamma (IFN-gamma) stimulatory
      activity of fractionated Taenia glycans and Lewis sugars with comparable glycan
      composition. Our data show that Taenia glycans and Lewis X pentasaccharide are
      potent stimulators of the Th-1 type cytokine IFN-gamma. We postulate that the
      terminal beta-(1-4)-galactose residue in Lewis X is associated with IFN-gamma
      stimulation from naive BALB/c mouse spleen and peritoneal exudate cells.
      Antibodies to toll-like receptors (TLRs) inhibited the Lewis X-induced IFN-gamma
      secretion. Lewis X up-regulated the expression of NF-kappaB p65 from naive spleen
      cells and IFN-gamma transcription in peritoneal exudate cells. These data
      demonstrate the ability of Lewis type helminth glycans to modulate host responses
      in a Th-1 direction via NF-kappaB p65, IFN-gamma and macrophage TLRs.

PMID- 17034863
TI  - An in vitro study of interactions between insulin-mimetic zinc(II) complexes and
      selected plasma components.
AB  - The speciations of some potent insulin-mimetic zinc(II) complexes of bidentate
      ligands: maltol and 1,2-dimethyl-3-hydroxypyridinone with (O,O) and picolinic
      acid with (N,O) coordination modes, were studied via solution equilibrium
      investigations of the ternary complex formation in the presence of small relevant
      bioligands of the blood serum such as cysteine, histidine and citric acid.
      Results show that formation of the ternary complexes, especially with cysteine,
      is favoured at physiological pH range in almost all systems studied. Besides
      these low molecular mass binders, serum proteins among others albumin and
      transferrin can bind zinc(II) or its complexes. Accordingly, the distribution of
      zinc(II) between the small and high molecular mass fractions of the serum was
      also studied by ultrafiltration. Modelling calculations relating to the
      distribution of zinc(II), using the stability constants of the ternary complexes
      studied and those of the serum proteins reported in the literature, confirmed the
      ultrafiltration results, namely, the primary role of albumin in zinc(II) binding
      among the low and high molecular mass components of the serum.

PMID- 17034864
TI  - Reduced expression of IL-6 and IL-1alpha mRNAs in secretory phase endometrium of
      women with recurrent miscarriage.
AB  - A diverse array of cytokines is implicated in regulating the immune adaptation
      and endometrial tissue remodelling events that facilitate successful embryo
      implantation and early placental development. The aim of this study was to
      evaluate expression of mRNAs encoding a panel of immunoregulatory cytokines in
      the endometrium of fertile women and women experiencing recurrent miscarriage
      using highly sensitive, quantitative RT-PCR assays. Endometrial biopsies were
      collected during the mid-secretory phase of the menstrual cycle from women
      classified as proven fertile (control; n=12) and women experiencing unexplained
      recurrent miscarriage (RM; n=9). Reduced IL-6 mRNA and reduced IL-1alpha mRNA
      were independently associated with recurrent miscarriage. Altered expression was
      evident after accounting for variation in the composition of endometrial biopsies
      by normalization of data to epithelial and mesenchymal cell-specific transcripts,
      cytokeratin-18 mRNA and vimentin mRNA, respectively. The relative abundance of
      mRNAs encoding LIF, GM-CSF, IFNgamma, IL-1beta, IL-4, IL-5, IL-10, IL-12p40,
      TNFalpha, TGFbeta1, TGFbeta2 and TGFbeta3 were not altered in recurrent
      miscarriage tissue. Associations between expression of IL-10, LIF, GM-CSF and
      TGFbeta2 suggest that regulatory circuits link the transcription of these
      cytokine genes. Inadequate expression of IL-6 and IL-1alpha mRNAs in endometrial
      tissue may predispose to recurrent miscarriage through a perturbed maternal
      immune response, effects on decidual tissue remodeling and angiogenesis, or
      dysregulated trophoblast differentiation and invasion. Quantitative RT-PCR assays
      for these cytokines in endometrial biopsies may be a realistic strategy for
      development of novel diagnostics for predisposition to recurrent miscarriage.

PMID- 17034865
TI  - Re: the role of topical nasal steroids in the treatment of children with otitis
      media with effusion and/or adenoid hypertrophy.

PMID- 17034866
TI  - The presentation and management of vascular rings: an otolaryngology perspective.
AB  - OBJECTIVE: To review the presentation and natural history of children with
      vascular rings and present management guidelines. METHODS: Retrospective study of
      tertiary care pediatric medical center charts from 1991 to 2002. RESULTS: There
      were 37 males and 27 females with a diagnosis of vascular rings. At presentation,
      91% of patients had airway symptoms and 47% had esophageal symptoms. Airway
      symptoms included stridor (63%), recurrent respiratory infections (47%),
      respiratory distress (19%), and cough (17%). The most common esophageal symptom
      was dysphagia (27%). Pre-operative studies included: echocardiography (96%),
      chest X-ray (93%), barium swallow (75%), magnetic resonance imaging (MRI) (60%),
      and computerized tomography (CT) scan of the chest (59%). Surgical management
      included open (n=25) and thoracoscopic (n=39) approach. Complications included
      recurrent laryngeal nerve injury in five patients (8%). CONCLUSION: Children with
      vascular rings present with respiratory and/or feeding difficulty. The evaluation
      should include chest X-ray, echocardiography, and barium swallow. Direct
      laryngoscopy and bronchoscopy are recommended to assess the degree of compression
      of the airway and/or esophagus, tracheomalacia, and vocal fold motion prior to
      intervention. Indication for surgical release is given when the diagnosis is made
      and can be assisted by advanced radiology studies. Surgical options include
      minimally invasive techniques involving either thoracoscopic or robotic-assisted
      repairs, as well as open procedures involving thoracotomy.

PMID- 17034867
TI  - Purification and immunogenicity study of human papillomavirus type 16 L1 protein
      in Saccharomyces cerevisiae.
AB  - Human papillomavirus 16 virus-like particle (HPV16 VLP) vaccines expressed in
      Saccharomyces cerevisiae are under Phase III trial and are expected to be on the
      market in the near future. We have established a convenient and economical system
      for the prophylactic study of vaccines derived from HPV16 VLPs, and
      neutralization tests to standardize HPV serological methodology as a measure of
      validation. To purify HPV16 VLPs, yeast cells expressing HPV16 L1 protein were
      cultured and purified on a small scale by ultracentrifugation and size-exclusion
      and cation-exchange chromatography using open columns. The highly purified HPV16
      L1 protein was identified by SDS-PAGE and Western blotting, and electron
      microscopic analysis confirmed that they self-assembled into VLPs. To test the
      efficacy of the purified VLPs as a vaccine and their ability to induce humoral
      immunity, we performed ELISA assays and observed a significant increase in the
      titer of anti-HPV16 VLPs antibodies in the sera of immunized mice. High anti
      HPV16 neutralizing titers were found in the sera of vaccinated mice, as measured
      by a SEAP-based pseudovirus neutralization assay. These results would be useful
      in the evaluation of the immunogenicity of HPV vaccine candidates, and provide an
      international reference standard for HPV serological methods.

PMID- 17034868
TI  - Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120
      human IgG1kappa monoclonal antibody, in HIV-1 infected cells.
AB  - The use of targeting moieties is a new and exciting field of scientific research
      for facilitating the specific delivery of therapeutic agents in HIV-infected
      patients. The interaction of a potential targeting moiety with its ligand is a
      crucial factor in the evaluation of a targeted approach for chemotherapeutic
      intervention. Therefore, we have further characterized the interaction between a
      potential targeting agent, the monoclonal human antibody F105, and its ligand
      gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We
      demonstrate the specificity of binding and entry of F105 to infected cells. F105
      was rapidly taken up into the cell and accumulated in the Golgi apparatus.
      Kinetic analysis of the F105-gp120 interaction revealed an equilibrium
      dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction
      where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher
      gp120 affinity. This was due to a slower dissociation as compared with the
      natural ligand. These data further underline the potential of monoclonal
      antibodies as targeting agents, and offer new insights into the possibility of
      F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1
      infected cells.

PMID- 17034869
TI  - Expression of the nucleoprotein gene of rabies virus for use as a diagnostic
      reagent.
AB  - The nucleoprotein (N) gene of rabies virus CTN strain, was cloned, sequenced and
      expressed in Escherichia coli as a fusion with maltose binding protein (MBP). The
      antigenicity of this recombinant MBP-N fusion protein was examined by Western
      blotting and enzyme linked immunosorbent assay (ELISA). Subsequently, an indirect
      ELISA was developed to detect rabies specific antibody levels. Using sera from
      naive and vaccinated animals the ELISA results were compared with virus
      neutralizing antibodies detected by a rapid fluorescent focus inhibition test
      (RFFIT). Neutralizing titres by RFFIT were found to correlate well with the OD
      values in the ELISA (r=0.9436) and the sensitivity and specificity of the ELISA
      were shown to be 93.4 and 100%, respectively. The data indicate that the
      recombinant MBP-N fusion protein can be expressed and isolated straightforwardly
      and may be useful as a safe and abundant source of antigen to monitor
      seropositivity in vaccinated canines.

PMID- 17034870
TI  - Control of antigen mass transfer via capture substrate rotation: an absolute
      method for the determination of viral pathogen concentration and reduction of
      heterogeneous immunoassay incubation times.
AB  - Immunosorbent assays are commonly employed as diagnostic tests in human
      healthcare, veterinary medicine and bioterrorism prevention. These assays,
      however, often require long incubation times, limiting sample throughput. As an
      approach to overcome this weakness, this paper examines the use of rotating
      capture substrates to increase the flux of antigen to the surface, thereby
      reducing the incubation time. To assess the capability of this approach, porcine
      parvovirus (PPV) was selectively extracted from solution by systematically
      varying the rotation rate of a gold substrate modified with a layer of anti-PPV
      monoclonal antibodies. The captured PPV were then directly imaged and quantified
      by atomic force microscopy. The benefits of substrate rotation are demonstrated
      by comparing an assay performed under stagnant conditions to one carried out with
      substrate rotation at 800 rpm, both for 10 min incubations at 25 degrees C. The
      use of rotation lowered the limit of detection to 3.4x10(4)TCID50/mL
      (approximately 80 fM) from 3.2x10(5)TCID50/mL (approximately 800 fM) under
      stagnant conditions. Results are also presented that show this strategy can be
      used: (1) to determine antigen concentrations without standards and (2) to
      establish the numerical relationship between quantal concentration units (e.g.,
      50% tissue culture infective dose (TCID50)) and quantitative concentration units
      (e.g., viruses/mL) The potential to broadly apply this technique to heterogeneous
      immunoassays is also briefly discussed.

PMID- 17034871
TI  - Multiplex PCR for the simultaneous detection of pseudorabies virus, porcine
      cytomegalovirus, and porcine circovirus in pigs.
AB  - The use of porcine organs is being developed as a means to alleviate the shortage
      of human organs for transplantation. Recommendations have been published for the
      microbiological specifications of organ-source pigs to reduce the possibility of
      a microorganism from pigs being inadvertently transferred to the recipient of the
      xenograft. The pseudorabies virus (PRV), porcine cytomegalovirus (PCMV), and
      porcine circovirus (PCV) are infectious agents in pigs that are considered to be
      of significance for the microbiological safety of xenotransplantation. A
      multiplex polymerase chain reaction (mPCR) was developed to detect and
      differentiate among PRV, PCMV, and PCV. The sensitivities of the multiplex PCR
      were 10(2.5) TCID(50)/ml for PRV, 10(1.8) TCID(50)/ml for PCMV, and 10(1.8)
      TCID(50)/ml for PCV. The lowest viral concentrations detected by single PCR were
      10(1.5) TCID(50)/ml for PRV, 10(1.0) TCID(50)/ml for PCMV, and 10(1.4)
      TCID(50)/ml for PCV2. Non-specific reactions were not observed when other
      viruses, bacteria, and Vero cells were used to assess the multiplex PCR. The
      multiplex PCR was effective in detecting various combinations of one or more of
      these viruses in pig specimens collected for xenotransplantation.

PMID- 17034872
TI  - Differential proinflammatory and angiogenesis-specific cytokine production in
      human pulmonary endothelial cells, HPMEC-ST1.6R infected with dengue-2 and dengue
      3 virus.
AB  - In this study, the ability of dengue virus serotypes 2 (DENV-2) and 3 (DENV-3) to
      infect and induce increased production of proinflammatory cytokines in a
      pulmonary endothelial cell line (HPMEC-ST1.6R) was investigated. This cell line
      exhibits the major constitutive and inducible endothelial cell characteristics,
      as well as angiogenic response. DENV-2 and DENV-3 infection was confirmed by an
      observed cytopathic effect (CPE), as well as RT-PCR and immunofluorescence
      assays. Increases in Th-1 and Th-2 cytokines IL-4, IL-8, IL-6, IL-10, GM-CSF, INF
      gamma, and tumor necrosis factor (TNF-alpha) within DENV-2- and DENV-3-infected
      cells were demonstrated using a microbead-based Bio-plex assay. Proinflammatory
      cytokine increases and the expression of a potent angiogenic inducer protein,
      VEGF were confirmed by dot-blot analysis using the TranSignal Human Angiogenesis
      Antibody Array. Dengue virus-infected HPMEC-ST1.6R cells exhibited an elongated
      cytoplasmic morphology, possibly representing a response to VEGF and activation
      of angiogenesis. The increased levels of Th-1 cytokines and VEGF in DENV-2 virus
      infected-HPMEC-ST1.6R could be distinguished from those infected by DENV-3. This
      suggests that cytokine patterns associated with DENV infections may be serotype
      and strain-specific. The experimental approaches described here could be
      developed further into a useful diagnostic tool for the characterization of
      dengue hemorrhagic fever cases, leading to enhancement of treatment therapy.

PMID- 17034873
TI  - Controlling hippocampal output: the central role of subiculum in hippocampal
      information processing.
AB  - The subiculum has a central position between the hippocampus proper and
      entorhinal and other cortices, as well as a range of subcortical structures. The
      functional role of subiculum within the hippocampal formation circuit remains
      largely unexplored and a theoretical and experimental consensus on its functions
      has yet to emerge. Presented here is a simple and speculative model of the
      functions of the subiculum, based partly on anatomical, behavioural and
      neurophysiological considerations. The model suggests, firstly, that the
      subiculum acts to amplify hippocampal output, given the prominent bursting
      behaviour of its neurons and, secondly, that there is a dorso-ventral segregation
      of function within the subiculum. The dorsal component appears principally
      concerned with the processing of information about space, movement and memory,
      whereas the ventral component appears to play a major regulatory role in the
      inhibition of the HPA axis.

PMID- 17034874
TI  - Response acquisition with delayed reinforcement in a rodent model of attention
      deficit/hyperactivity disorder (ADHD).
AB  - The spontaneously hypertensive rat (SHR) has been shown to exhibit behavioral
      characteristics analogous to those exhibited by humans diagnosed with attention
      deficit/hyperactivity disorder (ADHD). The present study was conducted to further
      evaluate the validity of the SHR model of ADHD by characterizing learning of a
      novel response under conditions of delayed reinforcement. Seven experimentally
      naive SHRs and a control group of seven normotensive Wistar-Kyoto (WKY) rats were
      exposed to a contingency where one lever press initiated pellet delivery after a
      15-s, resetting delay. Rats in both groups acquired lever pressing, and the
      pattern of acquisition was well described with a three-parameter, sigmoidal
      equation. Response acquisition was retarded in the SHRs; they took longer to
      acquire the behavior, exhibited lower response rates and earned fewer reinforcers
      over the course of the experiment. When reinforcer delivery was made immediate in
      a subsequent condition, the SHRs exhibited higher response rates than the WKY,
      suggesting that the lower rates of responding seen in the SHRs were due to the
      reinforcer delay. The results replicate previous research on response acquisition
      with delayed reinforcement and provide further validation of the SHR strain as a
      model of ADHD. Like humans diagnosed with ADHD, the SHRs appear to be
      hypersensitive to delayed consequences, which in the present context, interfered
      with learning a novel behavior.

PMID- 17034876
TI  - Characterization of the rabbit HKalpha2 gene promoter.
AB  - The HKalpha2 gene directs synthesis of the HKalpha2 subunit of the H(+), K(+)
      ATPase. In the kidney and colon, the gene is highly expressed and is thought to
      play a role in potassium (K(+)) conservation. The rabbit has been an important
      experimental system for physiological studies of ion transport in the kidney, so
      the rabbit HKalpha2 gene has been cloned and characterized. The genomic clones
      and the previously reported HKalpha2a and HKalpha2c subunit cDNAs provided a
      means to address several issues regarding the structure and expression of the
      HKalpha2 gene. First, the genomic organization established that the rabbit
      HKalpha2 gene was unambiguously homologous to the mouse HKalpha2 gene and the
      human ATP1AL1 gene. Second, the mapping of the transcription start site for the
      alternate transcript, HKalpha2c, confirmed that it was an authentic rabbit
      transcript. Finally, isolation of DNA from the 5' end of the HKalpha2 gene
      enabled us to initiate studies on its regulation in the rabbit cortical
      collecting duct. The promoter and two putative negative regulatory regions were
      identified and the effect of cell confluency on gene expression was studied.

PMID- 17034877
TI  - Peroxisomes and oxidative stress.
AB  - The discovery of the colocalization of catalase with H2O2-generating oxidases in
      peroxisomes was the first indication of their involvement in the metabolism of
      oxygen metabolites. In past decades it has been revealed that peroxisomes
      participate not only in the generation of reactive oxygen species (ROS) with
      grave consequences for cell fate such as malignant degeneration but also in cell
      rescue from the damaging effects of such radicals. In this review the role of
      peroxisomes in a variety of physiological and pathological processes involving
      ROS mainly in animal cells is presented. At the outset the enzymes generating and
      scavenging H2O2 and other oxygen metabolites are reviewed. The exposure of
      cultured cells to UV light and different oxidizing agents induces peroxisome
      proliferation with formation of tubular peroxisomes and apparent upregulation of
      PEX genes. Significant reduction of peroxisomal volume density and several of
      their enzymes is observed in inflammatory processes such as infections, ischemia
      reperfusion injury and hepatic allograft rejection. The latter response is
      related to the suppressive effects of TNFalpha on peroxisomal function and on
      PPARalpha. Their massive proliferation induced by a variety of xenobiotics and
      the subsequent tumor formation in rodents is evidently due to an imbalance in the
      formation and scavenging of ROS, and is mediated by PPARalpha. In PEX5-/- mice
      with the absence of functional peroxisomes severe abnormalities of mitochondria
      in different organs are observed which resemble closely those in respiratory
      chain disorders associated with oxidative stress. Interestingly, no evidence of
      oxidative damage to proteins or lipids, nor of increased peroxide production has
      been found in that mouse model. In this respect the role of PPARalpha, which is
      highly activated in those mice, in prevention of oxidative stress deserves
      further investigation.

PMID- 17034875
TI  - Modeling early cortical serotonergic deficits in autism.
AB  - Autism is a developmental brain disorder characterized by deficits in social
      interaction, language and behavior. Brain imaging studies demonstrate increased
      cerebral cortical volumes and micro- and macro-scopic neuroanatomic changes in
      children with this disorder. Alterations in forebrain serotonergic function may
      underlie the neuroanatomic and behavioral features of autism. Serotonin is
      involved in neuronal growth and plasticity and these actions are likely mediated
      via serotonergic and glutamatergic receptors. Few animal models of autism have
      been described that replicate both etiology and pathophysiology. We report here
      on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice
      that mimics neurochemical and structural changes in cortex and, in addition,
      displays a behavioral phenotype consistent with autism. Newborn male and female
      mice were depleted of forebrain 5-HT with injections of the serotonergic
      neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial
      forebrain bundle (mfb). Behavioral testing of these animals as adults revealed
      alterations in social, sensory and stereotypic behaviors. Lesioned mice showed
      significantly increased cortical width. Serotonin immunocytochemistry showed a
      dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex
      until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT
      transporters was significantly but transiently reduced in cerebral cortex of 5,7
      DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We
      hypothesize that increased cerebral cortical volume and sensorimotor, cognitive
      and social deficits observed in both 5-HT-depleted animals and in individuals
      with autism, may be the result of deficiencies in timely axonal pruning to key
      cerebral cortical areas.

PMID- 17034878
TI  - Peroxisomes and bile acid biosynthesis.
AB  - Peroxisomes play an important role in the biosynthesis of bile acids because a
      peroxisomal beta-oxidation step is required for the formation of the mature C24
      bile acids from C27-bile acid intermediates. In addition, de novo synthesized
      bile acids are conjugated within the peroxisome. In this review, we describe the
      current state of knowledge about all aspects of peroxisomal function in bile acid
      biosynthesis in health and disease. The peroxisomal enzymes involved in the
      synthesis of bile acids have been identified, and the metabolic and pathologic
      consequences of a deficiency of one of these enzymes are discussed, including the
      potential role of nuclear receptors therein.

PMID- 17034879
TI  - Voltage-gated calcium channels in genetic diseases.
AB  - Voltage-gated calcium channels (VGCCs) mediate calcium entry into excitable cells
      in response to membrane depolarization. During the past decade, our understanding
      of the gating and functions of VGCCs has been illuminated by the analysis of
      mutations linked to a heterogeneous group of genetic diseases called "calcium
      channelopathies". Calcium channelopathies include muscular, neurological, cardiac
      and vision syndromes. Recent data suggest that calcium channelopathies result not
      only from electrophysiological defects but also from altered alpha(1)/Ca(V)
      subunit protein processing, including folding, posttranslational modifications,
      quality control and trafficking abnormalities. Overall, functional analyses of
      VGCC mutations provide a more comprehensive view of the corresponding human
      disorders and offer important new insights into VGCC function. Ultimately, the
      understanding of these pathogenic channel mutations should lead to improved
      treatments of such hereditary diseases in humans.

PMID- 17034880
TI  - Exocytosis in neuroendocrine cells: new tasks for actin.
AB  - Most secretory cells undergoing calcium-regulated exocytosis in response to cell
      surface receptor stimulation display a dense subplasmalemmal actin network, which
      is remodeled during the exocytotic process. This review summarizes new insights
      into the role of the cortical actin cytoskeleton in exocytosis. Many earlier
      findings support the actin-physical-barrier model whereby transient
      depolymerization of cortical actin filaments permits vesicles to gain access to
      their appropriate docking and fusion sites at the plasma membrane. On the other
      hand, data from our laboratory and others now indicate that actin polymerization
      also plays a positive role in the exocytotic process. Here, we discuss the
      potential functions attributed to the actin cytoskeleton at each major step of
      the exocytotic process, including recruitment, docking and fusion of secretory
      granules with the plasma membrane. Moreover, we present actin-binding proteins,
      which are likely to link actin organization to calcium signals along the
      exocytotic pathway. The results cited in this review are derived primarily from
      investigations of the adrenal medullary chromaffin cell, a cell model that is
      since many years a source of information concerning the molecular machinery
      underlying exocytosis.

PMID- 17034881
TI  - Cysteine-string protein isoform beta (Cspbeta) is targeted to the trans-Golgi
      network as a non-palmitoylated CSP in clonal beta-cells.
AB  - Cysteine string proteins (CSPs) belong to the DnaJ-like chaperone family and play
      an important role in regulated exocytosis in neurons and endocrine cells. The
      palmitoylation of several residues in a cysteine string domain may anchor CSPs to
      the exocytotic vesicle surface and in pancreatic beta-cells, Cspalpha is
      localized on insulin containing large dense core vesicles (LDCVs). An isoform
      closely related to Cspalpha, Cspbeta, has been obtained from testis cell cDNA
      libraries. To gain insights on this isoform and more generally on the properties
      of CSPs, we compared Cspalpha and Cspbeta. In pull-down experiments, Cspbeta was
      able to interact to the same extent with two of the known Cspalpha chaperone
      partners, Hsc70 and SGT. Upon transient overexpression in clonal beta-cells,
      Cspbeta but not Cspalpha was mainly produced as a non-palmitoylated protein and
      mutational analysis indicated that domains distinct from the cysteine string are
      responsible for this difference. As Cspbeta remained tightly bound to membranes,
      intrinsic properties of CSPs are sufficient for interactions with membranes.
      Indeed, recombinant Cspalpha and Cspbeta were capable to interact with membranes
      even in their non-palmitoylated forms. Furthermore, overexpressed Cspbeta was not
      associated with LDCVs, but was localized at the trans-Golgi network. Our results
      suggest a possible correlation between the specific membrane targeting and the
      palmitoylation level of CSPs.

PMID- 17034882
TI  - Emerging perspectives in store-operated Ca2+ entry: roles of Orai, Stim and TRP.
AB  - Depletion of intracellular Ca2+ stores induces Ca2+ influx across the plasma
      membrane through store-operated channels (SOCs). This store-operated Ca2+ influx
      is important for the replenishment of the Ca2+ stores, and is also involved in
      many signaling processes by virtue of the ability of intracellular Ca2+ to act as
      a second messenger. For many years, the molecular identities of particular SOCs,
      as well as the signaling mechanisms by which these channels are activated, have
      been elusive. Recently, however, the mammalian proteins STIM1 and Orai1 were
      shown to be necessary for the activation of store-operated Ca2+ entry in a
      variety of mammalian cells. Here we present molecular, pharmacological, and
      electrophysiological properties of SOCs, with particular focus on the roles that
      STIM1 and Orai1 may play in the signaling processes that regulate various
      pathways of store-operated entry.

PMID- 17034883
TI  - Left ventricular noncompaction and mid-caviter narrowing associated with
      Ebstein's anomaly: three-dimensional transthoracic echocardiographic image.
AB  - An 50 year-old asymptomatic female was admitted to preoperative cardiovascular
      evaluation for noncardiac surgery. Two-dimensional transthoracic echocardiography
      demonstrated that left ventricular dimensions and ejection fraction were normal.
      The mitral valve was normal both in morphology and function. The attached margin
      of septal and anterior leaflet of the tricuspid valve was apically displaced. But
      right ventricle and right atrium dimensions were normal, and Doppler
      interrogation showed a slight tricuspid regurgitation. Two and three-dimensional
      transthoracic echocardiography showed prominent numerous trabeculations in the
      left ventricular apex. Colour flow Doppler studies confirmed the presence of
      blood flow within the trabeculations. Multi-plane three-dimensional transthoracic
      echocardiography showed a muscular band leading to left ventricular mid-caviter
      narrowing. Pulse wave Doppler echocardiography demonstrated that no
      intraventricular gradient existed. Ventricular noncompaction associated with
      Ebstein's malformation has been reported. But left ventricular noncompaction and
      mid-caviter narrowing associated with Ebstein's anomaly have not been reported so
      far.

PMID- 17034884
TI  - Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem
      cells.
AB  - This study sought to investigate the presence of oxytocin receptors and the
      possible biological role of oxytocin as an effective factor in the
      differentiation of embryonic stem cells (ESCs) into cardiomyocytes. Mouse ESCs
      were cultivated in hanging drops to form embryoid bodies (EBs). The EBs were then
      treated with and without oxytocin (experimental and control groups). Up to 30
      days after plating, contraction and beating frequency were monitored and
      evaluated daily. The growth characteristics of the ESC-derived cardiomyocytes
      were assessed by cardioactive drugs, immunocytochemistry, transmission electron
      microscopy (TEM) and reverse transcription-polymerase chain reaction (RT-PCR). In
      the experimental group, the percentage of the EBs with spontaneous contraction
      was significantly increased from 17th day onward. The spontaneous beating
      frequency of each EB in both groups was also changed with cardioactive drugs such
      as Bay K, carbachol, isopernaline and phenylephrine. However, in the experimental
      group, changes with isopernaline were more pronounced at the early and
      intermediate stages of cardiomyocyte development. The beating cells of both
      groups, stained positive with anti alpha-actinin, desmin, cardiac troponin I and
      connexin antibodies, and revealed similar ultrastructural features. Oxytocin
      receptors were detected on the ESCs and derived-differentiated cells. In
      addition, cardiac-specific genes such as cardiac alpha- and beta-myosin heavy
      chain, myosin light chain-2v, and atrial natriuretic factor were also detected in
      the ESC-derived differentiated cells of both groups. In the experimental group,
      all the specific genes, with the exception of alpha-myosin heavy chain, were more
      pronounced at the early stage of cardiomyocyte development. In conclusion,
      oxytocin has receptors on undifferentiated ESCs and derived differentiated cells,
      and in spite of better improvement of the EBs with spontaneous contraction, it
      can only promote the early maturation of ESC-derived cardiomyocytes in terms of
      chronotropic responses and expression of cardiac-specific genes, and have no
      effect on ultrastructural characteristics of cardiomyocytes in any stage of
      development.

PMID- 17034885
TI  - The impact of inflammation on the development, successful cardioversion,
      recurrence and/or perpetuation of atrial fibrillation.

PMID- 17034886
TI  - Subclinical carditis in rheumatic fever: a systematic review.
AB  - OBJECTIVE: Subclinical carditis (SCC)--pathological valvular regurgitation
      detected on echocardiography that is not evident clinically--has been reported in
      acute rheumatic fever (ARF), but its significance is unknown. We aimed to review
      the existing literature on the prevalence and outcome of SCC in ARF. METHODS: We
      conducted a systematic literature review using MEDLINE. RESULTS: Prevalences of
      SCC in ARF ranged from 0% (in one study only) to 53% in 23 articles. The weighted
      pooled prevalence of SCC in ARF was 16.8% (95%CI 11.9 to 21.6). This increased
      slightly to 18.1% (95%CI 11.1 to 25.2) by analysing only the 10 studies that
      applied full World Health Organization criteria for SCC diagnosis. The weighted
      pooled prevalence of persistence or deterioration of SCC 3 to 23 months after ARF
      diagnosis was 44.7% (95%CI 19.3 to 70.2) from 11 articles. CONCLUSION: SCC is
      relatively common in ARF. Although some studies suggest that SCC lesions may
      persist or deteriorate, the available data are insufficient and of poor quality,
      so no confident conclusions can be drawn about the prognosis of SCC. Until better
      studies are conducted, clinicians will have to make management decisions that are
      not evidence-based. These decisions will have important practical implications
      for the use of echocardiography acutely and during follow-up, diagnosis of ARF,
      and duration of secondary prophylaxis in patients with SCC.

PMID- 17034887
TI  - Management of feral domestic cats in the urban environment of Rome (Italy).
AB  - In Italy, which is rabies-free, the national Law No. 281 [Legge Nazionale 14
      agosto 1991. No. 281: Legge Quadro in materia di animali di affezione e
      prevenzione del randagismo. Gazz. Uff. Rep. Ital. no 203 del 30 agosto 1991: p.
      3] on the management of pets and on the control of feral cats has introduced the
      no-kill policy for this species. Thus, "trap-neuter-release" (TNR) programs have
      been carried out for >10 years. In this paper we present data on registered
      colonies and censused cats in Rome from 1991 to 2000; the results of the
      neutering campaign from 1991 to 2000; and a survey, on 103 cat colonies, on the
      effects of demographic control of urban feral-cat colonies in the city of Rome,
      carried out by the local Veterinary Public Services (VPS) in collaboration with
      the associations of cat care-takers. In 10 years almost 8000 were neutered and
      reintroduced in their original colony. The spay/neuter campaigns brought about a
      general decrease in cat number but the percentage of cat immigration (due to
      abandonment and spontaneous arrival) is around 21%. This suggests that all these
      efforts without an effective education of people to control the reproduction of
      house cats (as a prevention for abandonment) are a waste of money, time and
      energy.

PMID- 17034888
TI  - Medicare balance billing restrictions: impacts on physicians and beneficiaries.
AB  - Beginning in the late 1980s, states and the federal government restricted the
      ability of physicians to "balance bill" Medicare beneficiaries for charges in
      excess of the copayment and reimbursement amounts approved by Medicare. In this
      paper, I provide empirical evidence that this policy change resulted in a 9%
      reduction in out-of-pocket medical expenditures by elderly households. In spite
      of the change in marginal reimbursement to physicians, however, I find little
      evidence that the restrictions affected patterns of care. Thus, this restriction
      on the prices charged by physicians amounted to a transfer from affected
      physicians to affected patients.

PMID- 17034889
TI  - Use of a real time PCR assay for detection of the ctxA gene of Vibrio cholerae in
      an environmental survey of Mobile Bay.
AB  - Toxigenic Vibrio cholerae, the etiological agent of cholera, is a natural
      inhabitant of the marine environment and causes severe diarrheal disease
      affecting thousands of people each year in developing countries. It is the
      subject of extensive testing of shrimp produced and exported from these
      countries. We report the development of a real time PCR (qPCR) assay to detect
      the gene encoding cholera toxin, ctxA, found in toxigenic V. cholerae strains.
      This assay was tested against DNA isolated from soil samples collected from
      diverse locations in the US, a panel of eukaryotic DNA from various sources, and
      prokaryotic DNA from closely related and unrelated bacterial sources. Only Vibrio
      strains known to contain ctxA generated a fluorescent signal with the 5' nuclease
      probe targeting the ctxA gene, thus confirming the specificity of the assay. In
      addition, the assay was quantitative in pure culture across a six-log dynamic
      range down to <10 CFU per reaction. To test the robustness of this assay,
      oysters, aquatic sediments, and seawaters from Mobile Bay, AL, were analyzed by
      qPCR and traditional culture methods. The assay was applied to overnight alkaline
      peptone water enrichments of these matrices after boiling the enrichments for 10
      min. Toxigenic V. cholerae strains were not detected by either qPCR or
      conventional methods in the 16 environmental samples examined. A novel exogenous
      internal amplification control developed by us to prevent false negatives
      identified the samples that were inhibitory to the PCR. This assay, with the
      incorporated internal control, provides a highly specific, sensitive, and rapid
      detection method for the detection of toxigenic strains of V. cholerae.

PMID- 17034890
TI  - Ethical considerations of neuroscience research: the perspectives on neuroethics
      in Japan.
AB  - Recent technologies and developments in neuroscience have contributed to
      remarkable scientific discoveries, and have also raised many new philosophical,
      ethical, legal, and social issues. Research in "neuroethics" has identified
      various ethical issues, which will be difficult for current biomedical ethics to
      resolve from both an experimental and a social perspective, such as criminal
      applications of brain scans, incidental findings during non-clinical brain
      imaging, and cognitive enhancement. Although American and European neuroscience
      societies have demonstrated immediate, concrete reactions to these ethical
      issues, including academic conferences, study programs, and publications,
      Japanese neuroscientists have so far produced little response. Ethics is tightly
      linked with one's religion, nationality, culture, and social background, whereas
      science is tightly linked with the demand, economics, and politics of the society
      to which individuals belong. Taken together, it is important and necessary for
      Japanese neuroscientists to consider the ethical problems in Japanese
      neuroscience. In this paper, we first review the history of neuroethics in the
      world, and then report the less-developed ethical issues in the Japanese
      neuroscience community, focusing on neuroimaging and manipulative neuroscience as
      a first step in discussing how to apply principles in neuroethics to this rapidly
      progressing field of research.

PMID- 17034891
TI  - Cervical cancer treatment with a locally insertable controlled release delivery
      system.
AB  - Local delivery of cancer chemotherapeutics enables sustained drug levels at the
      site of action thereby reducing systemic side effects. A novel insertable
      polymeric drug delivery system for cervical cancer treatment is presented.
      Cisplatin, the first line of therapy employed for cervical cancers, was
      incorporated in a poly(ethylene-co-vinyl acetate) (EVAc) device that is similar
      to those currently used for vaginal contraceptive delivery. Cisplatin crystals
      were uniformly dispersed in the polymeric system without undergoing significant
      dissolution in the polymer matrix. Cisplatin dissolution from the devices was
      biphasic, consistent with a matrix-type controlled-release system with an initial
      rapid release phase followed by a slower, near linear release phase. Depending on
      the drug loading in the polymeric devices, the near-linear release phase varied
      in rate according to both empirical, linear curve-fitting (0.38+/-0.15 microg/day
      to 46.9+/-10.0 microg/day) and mechanistic, diffusion analysis based upon
      diffusion through a porous structure (D(app) from 1.3+/-0.5 x 10(-9) cm2/s to
      5.8+/-0.3 x 10(-12) cm2/s). The devices were tested for in vitro activity and
      found to be effective against both HPV positive and HPV negative cervical cancer
      cell lines. Preliminary studies indicate that this delivery system would be a
      good candidate for investigation as a choice of treatment in cervical cancers.

PMID- 17034892
TI  - Silk sericin-insulin bioconjugates: synthesis, characterization and biological
      activity.
AB  - When silk fiber derived from Bombyx mori was subjected to degumming treatments
      twice in water and subsequent degraded processing in slightly alkaline aqueous
      solution under high-temperature and high-pressure, the water-soluble silk sericin
      peptides (SS) with different molecular mass from 10 to 70 kDa were obtained. The
      sericin peptides could be conjugated covalently with insulin alone with cross
      linking reagent glutaraldehyde. The physicochemical properties of the silk
      sericin-insulin (SS-Ins) conjugates were determined by Enzyme-Linked
      Immunosorbent Assay (ELISA). The biological activities of SS-Ins bioconjugates
      were investigated in vitro and in vivo. The results in human serum in vitro
      indicated that the half-life of the synthesized SS-Ins derivatives was 2.3 and
      2.7 times more than that of bovine serum albumin-insulin (BSA-Ins) conjugates and
      intact insulin, respectively. The pharmacological activity of SS-Ins
      bioconjugates lengthened to 21 h in mice in vivo, which was over 4 times longer
      than that of the native insulin. The immunogenicity of silk sericin and the
      antigenicity of SS-Ins derivatives were not observed in both rabbits and mice.
      The bioconjugation of insulin with silk sericin protein evidently improved both
      physicochemical and biological stability of the polypeptide.

PMID- 17034893
TI  - Carotid atherosclerosis associated to metabolic syndrome but not BMI in healthy
      menopausal women.
AB  - BACKGROUND: Obesity and the metabolic syndrome (MS) frequently coexist. Both are
      apparently associated to cardiovascular disease. However, the contribution of
      obesity to cardiovascular risk, independent of the presence of the metabolic
      syndrome, remains controversial. The purpose of this study was to investigate
      whether the subclinical carotid atherosclerosis prevalence is different in obese
      postmenopausal women with and without the metabolic syndrome. METHODS: On the
      basis of consecutive recruitment, 313 postmenopausal women underwent a clinical,
      biochemical and ultrasound characterization. Women affected by cardiovascular
      disease or diabetes were excluded from the study. RESULTS: Among enrolled women
      the metabolic syndrome and body mass index (BMI) resulted strongly associated,
      but only metabolic syndrome was associated with carotid atherosclerosis, a well
      known marker of cardiovascular disease. Similarly, increases in BMI unit (normal
      to overweight to obese) were not associated with carotid atherosclerosis whereas
      metabolic status (normal to metabolic syndrome) conferred an approximate three
      fold adjusted odds of carotid atherosclerosis. CONCLUSIONS: The metabolic
      syndrome but not obesity is associated to carotid atherosclerosis in
      postmenopausal women. Although it remains prudent to recommend weight loss in
      overweight and obese women, evaluation and control of metabolic risk factors
      should be considered the main goal to prevent cardiovascular and cerebrovascular
      disease.

PMID- 17034894
TI  - Work stress and low emotional support is associated with increased risk of future
      type 2 diabetes in women.
AB  - A case-referent study nested within a population-based health survey investigated
      the associations between psychosocial stress, such as work stress and low
      emotional support, and future development of type 2 diabetes among occupationally
      working middle-aged men and women. All participants in a health survey conducted
      during 1989-2000 (n=33,336) in Umea in northern Sweden, were included. We
      identified 191 cases, who were not diabetic initially but were diagnosed with
      type 2 diabetes after 5.4+/-2.6 years. Two age- and sex-matched referents were
      selected for each case. Multivariate logistic regression analyses and interaction
      effects between variables were evaluated. In women, passive or tense working
      situations were associated with future type 2 diabetes with odds ratios 3.6 (95%
      confidence interval 1.1-11.7) and 3.6 (1.0-13.3), respectively, and also low
      emotional support 3.0 (1.3-7.0). These associations were not seen in men. In
      women, they remained after adjustment for BMI, civil status and educational
      level, and there were also tendencies for interactions between work stress and
      low emotional support. In conclusion, work stress and low emotional support may
      increase the risk of type 2 diabetes in women, but not in men. These findings
      contribute to our understanding of psychosocial stress as potential risk factors
      for type 2 diabetes in a Swedish population.

PMID- 17034895
TI  - Hepatitis A virus infection suppresses hepatitis C virus replication and may lead
      to clearance of HCV.
AB  - BACKGROUND/AIMS: The significance of hepatitis A virus (HAV) super-infection in
      patients with chronic hepatitis C had been a matter of debate. While some studies
      suggested an incidence of fulminant hepatitis A of up to 35%, this could not be
      confirmed by others. METHODS: We identified 17 anti-HCV-positive patients with
      acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a
      single center over a period of 12 years. RESULTS: Importantly, none of the anti
      HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected
      by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in
      65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating
      suppression of HCV replication during hepatitis A. Previous HAV infection had no
      effect on HCV replication. After recovery from hepatitis A, an increased HCV
      replication could be demonstrated for 6 out of 9 patients with serial
      quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative
      after clearance of HAV throughout follow-up of at least 2 years. CONCLUSIONS: HAV
      super-infection is associated with decreased HCV-RNA replication which may lead
      to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent
      in patients with chronic hepatitis C recruited at a tertiary referral center.

PMID- 17034896
TI  - Genetic mutation in hepatic adenoma: seeing is believing.

PMID- 17034897
TI  - Juvenile hemochromatosis.

PMID- 17034898
TI  - Priority setting at the micro-, meso- and macro-levels in Canada, Norway and
      Uganda.
AB  - The objectives of this study were (1) to describe the process of healthcare
      priority setting in Ontario-Canada, Norway and Uganda at the three levels of
      decision-making; (2) to evaluate the description using the framework for fair
      priority setting, accountability for reasonableness; so as to identify lessons of
      good practices. METHODS: We carried out case studies involving key informant
      interviews, with 184 health practitioners and health planners from the macro
      level, meso-level and micro-level from Canada-Ontario, Norway and Uganda
      (selected by virtue of their varying experiences in priority setting). Interviews
      were audio-recorded, transcribed and analyzed using a modified thematic approach.
      The descriptions were evaluated against the four conditions of "accountability
      for reasonableness", relevance, publicity, revisions and enforcement. Areas of
      adherence to these conditions were identified as lessons of good practices; areas
      of non-adherence were identified as opportunities for improvement. RESULTS: (i)
      DESCRIPTION: at the macro-level, in all three countries, cabinet makes most of
      the macro-level resource allocation decisions and they are influenced by
      politics, public pressure, and advocacy. Decisions within the ministries of
      health are based on objective formulae and evidence. International priorities
      influenced decisions in Uganda. Some priority-setting reasons are publicized
      through circulars, printed documents and the Internet in Canada and Norway. At
      the meso-level, hospital priority-setting decisions were made by the hospital
      managers and were based on national priorities, guidelines, and evidence.
      Hospital departments that handle emergencies, such as surgery, were prioritized.
      Some of the reasons are available on the hospital intranet or presented at
      meetings. Micro-level practitioners considered medical and social worth criteria.
      These reasons are not publicized. Many practitioners lacked knowledge of the
      macro- and meso-level priority-setting processes. (ii) Evaluation-relevance:
      medical evidence and economic criteria were thought to be relevant, but lobbying
      was thought to be irrelevant. Publicity: all cases lacked clear and effective
      mechanisms for publicity. REVISIONS: formal mechanisms, following the planning
      hierarchy, were considered less effective, informal political mechanisms were
      considered more effective. Canada and Norway had patients' relations officers to
      deal with patients' dissensions; however, revisions were more difficult in
      Uganda. Enforcement: leadership for ensuring decision-making fairness was not
      apparent. CONCLUSIONS: The different levels of priority setting in the three
      countries fulfilled varying conditions of accountability for reasonableness, none
      satisfied all the four conditions. To improve, decision makers at the three
      levels in all three cases should engage frontline practitioners, develop more
      effectively publicized reasons, and develop formal mechanisms for challenging and
      revising decisions.

PMID- 17034899
TI  - Functionality of unspliced XBP1 is required to explain evolution of overlapping
      reading frames.
AB  - Eukaryotic genes with overlapping reading frames exemplify some of the most
      striking biological phenomena. Transcript of one such gene, the gene encoding X
      box protein (XBP1), has evolved a mechanism for "on-demand" switching of
      translation between two overlapping reading frames. Despite the existence of this
      elaborate system, only one reading frame was believed to be functional. Here, we
      show that XBP1 evolves in a fashion that is only consistent with functionality of
      both reading frames. Our study provides a novel evolutionary framework for the
      analysis of loci with overlapping reading frames, which can be used for
      identification and analyses of novel dual-coding genes.

PMID- 17034900
TI  - From Mendelian to molecular genetics: the Xiphophorus melanoma model.
AB  - In human tumor biopsies it is almost impossible to pinpoint the particular
      molecular abnormalities that determine neoplasia. In animal models where
      tumorigenesis is initiated by clearly defined genetic events, it is possible to
      study the genes and their functions that make a normal cell become a fully
      malignant cancer cell. In the fish Xiphophorus, melanoma can be initiated by
      simple crossings, and the signaling pathways that govern tumor growth and
      progression can be delineated. This model offers the prospect of obtaining a
      complete picture of the molecular changes and regulatory networks underlying
      tumor formation, which should contribute to a better understanding of some
      general principles of cancer biology, and identify new targets for melanoma
      research in particular.

PMID- 17034901
TI  - Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk
      for lung cancer in never- and ever-smokers.
AB  - This case-control study examines the association between lung cancer and genetic
      polymorphisms in two base excision repair (BER) genes, XRCC1 and APEX1 and two
      genes involved in homologous recombination repair (HR), XRCC3 and NBS1. Never
      smoking lung cancer patients were recruited, and also the next diagnosed ever
      smoking case of the same gender and age group. Controls were recruited from the
      regional population register, frequency matched to cases by hospital catchment
      area, gender, age group and smoking category. As a result more than 70% of the
      study population were women. A total of 331 individuals were analysed. Presence
      of the XRCC1 399Gln allele was associated with a significantly decreased risk for
      lung cancer among non-smoking women (odds ratio (OR) 0.4, 95% confidence interval
      (CI) 0.2-0.9). No significant effect was seen with the APEX1 polymorphism. Women
      smokers carrying the XRCC3 241Met allele showed a significantly decreased risk
      for lung cancer (OR 0.3, CI 0.2-0.7). The NBS1 185Gln allele was significantly
      associated with an increased risk for lung cancer among non-smoking women (OR
      2.2, CI 1.0-4.8) and low-dose smoking women (OR 4.8, CI 1.5-15.7). The protective
      effect of the variant XRCC3 241Met allele was strengthened when combined with the
      low-risk Glu185 allele of the NBS1 gene. Smokers (OR 0.38, CI 0.16-0.90) and
      women (OR 0.42, CI 0.21-0.85) with at least three low-risk alleles in these two
      HR genes showed a significantly decreased risk for lung cancer. Thus, in spite of
      a relatively small study population, this study, including a comparatively large
      number of never-smokers and women, presents several novel aspects on genetic
      susceptibility to lung cancer. Our results show that the genetic variation in
      XRCC1, XRCC3 and NBS1 influence lung cancer susceptibility among women, and that
      combinations of risk alleles in the two HR genes can enhance the effects.

PMID- 17034902
TI  - Motivational state modulates the hedonic value of food images differently in men
      and women.
AB  - We investigated visual alimentary alliesthesia in non-fasted (N = 369) and fasted
      participants (N = 257) viewing photographs of food. Fasted participants were
      asked to not eat for 12 h before the session. Each participant was shown food and
      non-food images and rated each image on valence (i.e., pleasantness). The
      strongest evidence of alliesthesia was found in women. Fasting enhanced the
      pleasantness of food images for each of the food categories in women, although
      this alliesthesia effect was smaller in response to dessert foods compared to the
      less-pleasantly-rated food categories. In addition, non-fasting women exhibited
      significant positive correlations between hunger ratings and valence ratings of
      three of the five food categories. There was no significant difference in valence
      ratings of food between fasting vs. non-fasting men, but non-fasting men showed
      correlations between hunger and valence that were similar to those observed among
      the women. No evidence was found of hunger- or fasting-induced enhancement of
      hedonic ratings of non-foods in women or men, indicating the specificity of the
      alliesthesia effect for the food images only.

PMID- 17034903
TI  - Attitudes towards disability in an undergraduate nursing curriculum: the effects
      of a curriculum change.
AB  - Through improved technology and treatment and ongoing de-institutionalisation,
      nurses will encounter growing numbers of people with disabilities in the New
      Zealand community and hospitals. Quality of nursing care is influenced by
      attitude and this study was to evaluate the effect of a curriculum change on the
      attitudes of two different streams of student nurses towards people with
      disabilities. During the year 2002 a focused disability unit was introduced to
      the revised undergraduate nursing curriculum of a major educational institution
      in New Zealand. The opportunity arose to consider student nurses' attitudes
      toward disabled people, comparing two streams of students undertaking two
      different curricula. A convenience sample of students completed the attitudes
      toward disabled persons questionnaire form B (Yuker, H.E., Block, J.R., Younng,
      J.H., 1970. The Measurement of Attitudes Toward Disabled Persons. INA Mend
      Institute, New York), prior to and on completion of their relevant disability
      unit. No statistically significant difference in scores was demonstrated. A
      number of possible reasons for this are suggested.

PMID- 17034904
TI  - Nursing students' mathematic calculation skills.
AB  - This mixed method study used a pre-test/post-test design to evaluate the efficacy
      of a teaching strategy in improving beginning nursing student learning outcomes.
      During a 4-week student teaching period, a convenience sample of 54 sophomore
      level nursing students were required to complete calculation assignments, taught
      one calculation method, and mandated to attend medication calculation classes.
      These students completed pre- and post-math tests and a major medication
      mathematic exam. Scores from the intervention student group were compared to
      those achieved by the previous sophomore class. Results demonstrated a
      statistically significant improvement from pre- to post-test and the students who
      received the intervention had statistically significantly higher scores on the
      major medication calculation exam than did the students in the control group. The
      evaluation completed by the intervention group showed that the students were
      satisfied with the method and outcome.

PMID- 17034905
TI  - Energy requirements in frail elderly people: a review of the literature.
AB  - This review collates studies of healthy, sick, underweight (BMI < or = 21 kg/m2)
      and very elderly people (> or = 90 yr), in whom resting energy expenditure (REE)
      was measured using indirect calorimetry. We have observed the following: (1) REE,
      when adjusted for differences in both body weight and fat-free mass (FFM), is
      similar in healthy and in sick elderly people being 20 and 28 kcal/kg of FFM per
      day, respectively, (2) their nutritional status influences their energy
      requirements given that weight-adjusted REE increases in line with a decrease in
      BMI, (3) total energy expenditure is lower in sick elderly people given that
      their physical activity level, i.e. the ratio of total energy expenditure to REE,
      is reduced during disease averaging at 1.36, (4) energy intake (EI) being only
      1.23 x REE is insufficient to cover energy requirements in sick elderly patients,
      whereas the EI of healthy elderly people appears sufficient to cover
      requirements, and finally, (5) gender ceases to be a determinant of REE in people
      aged 60 yr or over, with the Harris & Benedict equation capable of accurately
      predicting mean REE in this population, whether healthy or sick.

PMID- 17034906
TI  - Increased risk of chronic suppurative lung disease after measles or pertussis in
      non-vaccinated children.
AB  - We retrospectively analysed 23 children originating from Campania--Southern Italy
      -with recurrent pneumonia and chest high-resolution computed tomography (HRCT)
      proven bronchiectasis. In six patients (26%) who had not undergone measles or
      pertussis vaccination, recurrent pneumonia started after an episode of lower
      respiratory tract infection complicating pertussis (n=2) or measles (n=4),
      contracted at a mean age of 3.6 years. Thirty-three percent (2/6) and 67% (4/6)
      of the patients had bilateral or monolobar disease, respectively, while in two
      subjects (33%) bronchiectasis were found in all lobes. These findings indicate an
      increased risk of developing bronchiectasis after measles or pertussis.

PMID- 17034907
TI  - Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal
      disease efficacy of conjugate vaccine in children.
AB  - Immunological evaluation of the clinical impact of vaccines designed to protect
      against infection by Streptococcus pneumoniae requires measurement of serotype
      specific functional antibodies. We describe the development and validation of a
      viable pneumococcal opsonophagocytosis assay (OPA) that can be used for routine
      serological analysis of paediatric immune responses after immunization. OPA
      seropositivity (%> or =8 threshold) reflected well invasive pneumococcal disease
      (IPD) effectiveness. In contrast, the 22F inhibition ELISA seropositivity (%> or
      =0.20microg/ml threshold) overestimated (19F) or underestimated (6B, 23F, 6A) IPD
      effectiveness for several serotypes. The seropositivity as estimated by a
      standardized and highly reproducible OPA was predictive for the serotype-specific
      IPD efficacy of pneumococcal conjugate vaccines.

PMID- 17034908
TI  - Animal models for protein pneumococcal vaccine evaluation: a summary.
AB  - This paper summarizes the discussion and viewpoints from a recent meeting
      regarding the use of animal models for pneumococcal protein vaccines. A wide
      spectrum of workers in this field met to discuss the animal species to be used in
      models, the approach of passive and active protection, the characteristics of
      challenge pneumococcal strains, inducing disease syndromes by a variety of routes
      of challenge, the determination of specific endpoints to assess effectiveness,
      the correlates of protection and other details of experimental design and
      analysis. Vaccine regulatory aspects were discussed. The document concludes with
      a series of questions that remain to be investigated.

PMID- 17034909
TI  - Establishing the health and economic impact of influenza vaccination within the
      European Union 25 countries.
AB  - BACKGROUND: In 2003, the World Health Assembly (WHA) issued a resolution for
      prevention and control of influenza pandemics and annual epidemics, which urges
      the European Union 25 (EU-25) Member States to (1) establish and implement
      strategies to increase vaccination coverage of all people at high risk, including
      the elderly and people with underlying disease, with the goal of attaining
      vaccination coverage of the elderly population of at least 50% by 2006 and 75% by
      2010; (2) to assess the disease burden and economic impact of annual influenza
      epidemics as a basis for framing and implementing influenza prevention policies.
      This resolution was reinforced by the European Union (EU), where Member States
      agreed to make additional efforts to improve uptake on their territory in
      accordance with their own recommendations and to achieve the World Health
      Organisation (WHO) target of 75% in high risk groups before 2010. It was also
      noted that the changing demographic profile of the EU population would result in
      an increasing number of elderly people falling within the current target groups.
      OBJECTIVES: To establish the number of people who may be eligible for influenza
      vaccination in the EU, and estimate the costs and consequences of not vaccinating
      this population for five EU Member States, France, Germany, Italy, Spain, and the
      UK. METHODS: A mathematical model has previously been developed, in which vaccine
      distribution data are combined with demographic and health economics data to
      model the public health consequences of influenza and possible intervention
      strategies. We have extended that model using specific EU-25 demographic data on
      populations at risk of influenza during the inter-pandemic period. For each
      country, the total population and age breakdown was calculated to estimate the
      percentage of the population that falls under the WHA recommendations. Other
      target groups for influenza vaccination were identified by analysing estimating
      the proportion of the population with respiratory or cardiovascular related
      diseases, diabetes, AIDS or transplantation, as well as health care
      professionals. Target population size and possible vaccination coverage rates
      across the EU-25 Member States, along with the potential cost and health
      consequence impact is estimated. RESULTS: For the EU-25, it was estimated that up
      to 49.1% of the population (or 223.4 million people) should be vaccinated against
      influenza. This ranged from 41.6% in Cyprus to 56.4% in the UK. There were, on
      average, 174 vaccine doses distributed per 1000 population within the EU-25,
      which leads to an average vaccination rate of the target population of 35.4%
      based on current supply constraints. As a consequence, up to 144.4 million people
      who could be considered "at risk" may not currently be vaccinated. Implementing a
      100% vaccination rate programme for all risk groups across the EU-25 would lead
      to an estimated reduction of number of influenza cases of 7.22 million, 1.96
      million reduced PCP visits for influenza treatment, 796,743 less hospital
      admissions and 68,537 fewer influenza related deaths for all EU-25 countries. The
      implementation of a 100% vaccination rate programme for all risk groups in
      France, Germany, Italy, Spain and UK would require an additional 1.52 billion
      Euro. This would result in estimated savings of 39.45 million Euro of reduced
      primary care visits and further savings of 1.59 billion Euro in reduced
      hospitalisations respectively in these countries. CONCLUSIONS: There is a gap
      between current vaccination coverage and the EU recommendations. The public
      health consequences of low vaccination coverage include increased morbidity,
      hospitalisations and mortality associated with influenza-related complications.
      This model is a powerful tool to: (1) support EU public health officials in
      implementing recommendations; (2) to visualize the need for increased vaccination
      rates for better influenza control; (3) the consequences of low vaccine coverage.

PMID- 17034910
TI  - Reverse radial artery bone flap reconstruction of segmental metacarpal losses.
AB  - A vascularised bone segment of the distal radius was harvested as a distally
      based flap to treat segmental metacarpal bone loss in three patients. One
      reconstruction followed resection of a giant cell tumour excision and the other
      two were to replace traumatic bone loss. The bone defects were in the second
      metacarpal in two cases and in the second and third metacarpal in one case and
      included three shaft and one distal metacarpal reconstruction. The mean length of
      the metacarpal defects was 6 cm. All of the flaps survived and no complications
      occurred at the donor site. Clinical and radiological union was established in
      all cases after an average of 3 months.

PMID- 17034911
TI  - Diaphyseal non-union in the distal phalanx of a child.
AB  - Non-union after finger fracture is an infrequent complication. Although well
      described in adults, there are few reported cases in children. We describe a 6
      year-old boy who presented with a non-union of the diaphysis of the distal
      phalanx three years after a finger tip crush injury.

PMID- 17034912
TI  - The effect of short-term dependency and immobility on skin temperature and colour
      in the hand.
AB  - The effects of short-term dependency and immobility on skin temperature were
      assessed in two experiments. In the first study, ten volunteers hung their left
      arm dependent and motionless while using their right hand for light office work.
      After 30 minutes, the dependent left hands were cooler (mean=0.9 degrees C: 95%
      CI=0.7-1.1) than the active right hands and exhibited a deeper colour with
      significantly increased green intensity (P=0.03) as assessed on digital images.
      In the second study, seven volunteers submerged both their hands in water at 15
      degrees C for 15 minutes. The left arm was then left dependent and motionless
      while the right hand was placed on the table and its fingers were flexed and
      extended every 10 seconds. The left hands remained cooler than the right and were
      a median of 3.6 (range 2.9-4.5) degrees C cooler after 60 minutes. These studies
      demonstrate that skin temperature and colour differences between the hands, which
      are sometimes used to support the diagnosis of CRPS-1, can be produced and
      maintained by short-term immobility and dependency of the hand.

PMID- 17034913
TI  - The trapezium: a new location for an aneurysmal bone cyst.

PMID- 17034914
TI  - Halogenated organic compounds in archived whale oil: a pre-industrial record.
AB  - To provide additional evidence that several halogenated organic compounds (HOCs)
      found in environmental samples are natural and not industrially produced, we
      analyzed an archived whale oil sample collected in 1921 from the last voyage of
      the whaling ship Charles W. Morgan. This sample, which pre-dates large-scale
      industrial manufacture of HOCs, contained two methoxylated polybrominated
      diphenyl ethers (MeO-PBDEs), five halogenated methyl bipyrroles (MBPs), one
      halogenated dimethyl bipyrrole (DMBP), and tentatively one dimethoxylated
      polybrominated biphenyl (diMeO-PBB). This result indicates, at least in part, a
      natural source of the latter compounds.

PMID- 17034915
TI  - Integrated effects of air pollution and climate change on forests: a northern
      hemisphere perspective.
AB  - Many air pollutants and greenhouse gases have common sources, contribute to
      radiative balance, interact in the atmosphere, and affect ecosystems. The impacts
      on forest ecosystems have been traditionally treated separately for air pollution
      and climate change. However, the combined effects may significantly differ from a
      sum of separate effects. We review the links between air pollution and climate
      change and their interactive effects on northern hemisphere forests. A
      simultaneous addressing of the air pollution and climate change effects on
      forests may result in more effective research, management and monitoring as well
      as better integration of local, national and global environmental policies.

PMID- 17034916
TI  - Smoking, traumatic event exposure, and post-traumatic stress: a critical review
      of the empirical literature.
AB  - The current review critically examines the extant empirical literature focused on
      the associations among cigarette smoking, trauma, and post-traumatic stress.
      Inspection of the extant literature suggests that smoking rates are significantly
      higher among persons exposed to a traumatic event relative to those without such
      exposure. Moreover, smoking rates appear particularly high among persons with
      post-traumatic stress disorder (PTSD). In terms of the direction of this
      relation, evidence most clearly suggests that post-traumatic stress is involved
      in the development of smoking. Significantly less is known about the role of
      trauma and PTSD in terms of cessation outcome. Limitations of extant work,
      clinical implications, and key directions for future study are delineated.

PMID- 17034917
TI  - Relationship between machine-derived smoke yields and biomarkers in cigarette
      smokers in Germany.
AB  - In order to determine whether smokers of cigarettes in the contemporary yield
      ranges of the German market (0.1-1.0mg nicotine, 1-10mg tar) differ in their
      actual exposure to various smoke constituents, we performed a field study with
      274 smokers and 100 non-smokers. The following biomarkers were determined: In 24
      h urine: Nicotine equivalents (molar sum of nicotine, cotinine, trans-3'
      hydroxycotinine and their respective glucuronides), 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL, metabolite of the tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK), 3-hydroxypropylmercapturic
      acid (metabolite of acrolein), trans,trans-muconic acid, S-phenylmercapturic acid
      (metabolites of benzene), 1-hydroxypyrene (metabolite of pyrene); in saliva:
      Cotinine and trans-3'-hydroxycotinine; in exhaled air: Carbon monoxide; in blood:
      Methyl-, hydroxyethyl-, cyanoethyl- (biomarker of acrylonitrile) and
      carbamoylethylvaline (biomarker of acrylamide) hemoglobin adducts. All biomarkers
      were found to be significantly higher in smokers compared to non-smokers and
      showed strong correlations with the daily cigarette consumption. Biomarker levels
      and per cigarette increases in smokers were at most weakly related to the machine
      derived smoke yields. It is concluded that machine-derived yields of cigarettes
      from the contemporary German cigarette market have little or no impact on the
      actual smoking-related exposure determined by suitable biomarkers.

PMID- 17034918
TI  - Dignity and health: a review.
AB  - Attention to dignity is thriving in health. However, much of this recent
      discourse ignores the broader scholarship pertaining to dignity. The purpose of
      this review is to synthesize a wide range of multidisciplinary writing in order
      to put recent discussions of dignity and health into a broader context. The
      review explicates two main meanings of dignity-human dignity and social dignity,
      and looks at how these two ideas are used in the arenas of human rights, law,
      social justice, bioethics, and clinical care, and suggests some implications of
      these meanings and uses for health research and advocacy.

PMID- 17034919
TI  - Some issues in the provision of adult bereavement support by UK hospices.
AB  - This paper considers some issues in the provision of adult bereavement support in
      UK hospices. The paper is based on the findings of a multi-method study conducted
      in two phases over 30 months (2003-2005) to examine the nature and quality of
      adult bereavement support in UK hospices from the perspectives of bereaved people
      and professional and volunteer bereavement workers [Field, Reid, Payne, & Relf
      (2005). Adult Bereavement Support in Five Hospices in England. Sheffield, UK:
      Palliative and End-of-Life Care Research Group, University of Sheffield.
      (Available from Professor Payne)]. It discusses the importance of continuity
      between pre-bereavement and bereavement support, the integration of bereavement
      services within hospices and the involvement of volunteers in bereavement
      support. It then discusses the engagement of UK hospices in the broader
      development of bereavement support. Although hospices have developed expertise in
      supporting bereaved people, our research suggests that they have not had a major
      impact on other health service providers, such as general practitioners and
      distinct nurses and staff in acute hospital trusts, in this area.

PMID- 17034920
TI  - Why psychosis needed something more than just the evolution of language.

PMID- 17034921
TI  - Radiological impact of dietary intakes of naturally occurring radionuclides on
      Pakistani adults.
AB  - Daily dietary intakes of three naturally occurring long-lived radionuclides
      (232)Th, (238)U and (40)K were estimated for the adult population of Pakistan
      using neutron activation analysis (NAA), inductively coupled plasma mass
      spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), respectively. The
      daily intakes of (232)Th ranged from 4 to 29 mBq, (238)U ranged from 17 to 82 mBq
      and (40)K ranged from 51 to 128 Bq. The geometric means of these intakes were 10
      mBqd(-1) for (232)Th, 33 mBqd(-1) for (238)U and 78.5 Bqd(-1) for (40)K. The
      measured values give annual committed effective doses of 0.80, 0.53 and 178.75
      microSvyr(-1) for (232)Th, (238)U and (40)K, respectively to Pakistani
      population. The net radiological impact of these radionuclides is 180.08
      microSvyr(-1). This value gives cancer risk factor of 4.5 x 10(-4) and loss of
      life expectancy of 0.87 days only. Whereas ICRP cancer risk factor for general
      public is 2.5 x 10(-3) and total risk involve from the all natural radiation
      sources based on global average annual radiation dose of 2.4 mSvyr(-1) is 6.0 x
      10(-3). The estimated cancer risk shows that probability of increase of cancer
      risk from daily Pakistani diet is only a minor fraction of ICRP values.
      Therefore, the diet does not pose any significant health hazard and is considered
      radiologically safe for human consumption.

PMID- 17034922
TI  - Detection of micronucleus and abnormal nucleus in erythrocytes from the gill and
      kidney of Labeo bata cultivated in sewage-fed fish farms.
AB  - Determination of genotoxic effect in fish, micronucleus test as well as the study
      of the abnormal shape of nuclei is a suitable measure, in which the presence or
      absence of genotoxins can be detected in water. In the present study, micronuclei
      and abnormal nuclei frequencies were scored in the gill and kidney erythrocytes
      of the fish Labeo bata grown in the sewage-fed fish farms of East Calcutta
      wetlands. Three experimental sites were chosen, namely, Bantala, Chowbaga and
      Chingrihata (basically these sites have sewage-fed fishponds), which were
      compared with fishponds of no sewage influence as the control area. Highly
      significant differences (P<0.001) were noticed for micronucleus frequencies in
      the gill and kidney erythrocytes of experimental fishes, where kidney
      erythrocytes showed an increased value than gill erythrocytes without any
      statistical differences. The frequencies of nuclear abnormalities such as
      necrotic cells, apoptotic cells, notch nucleated cells and binucleated cells were
      also counted separately for gill and kidney erythrocytes, in which significantly
      (P<0.001, P<0.01, P<0.05) increased values were obtained in comparison to control
      populations. These genotoxicity results confirmed that the sewage-fed ponds
      contain genotoxic metals such as Cr, Zn, Cu, Pb, Mn, Fe through wastewater and
      sludge because of the direct use of sewage water without pretreatment which may
      lead to health risks among humans through chronic consumption of fish from these
      experimental fish ponds. Other vertebrates grown in sewage-fed ponds may also
      suffer a certain amount of genotoxic substances.

PMID- 17034923
TI  - Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and
      drug metabolism and potentiation of carcinogenic activity of N
      nitrosodimethylamine in kidney and lung.
AB  - There are limited number of studies regarding the influence of diabetes on the
      regulation of cytochrome P450s and associated drug metabolizing enzyme activities
      especially in extrahepatic tissues such as kidney. However, there is almost no
      such study in lung. Alloxan-induced diabetes did not change CYP2B4 expression as
      measured with immunoblot analysis and associated enzyme, benzphetamine N
      demethylase, activity in rabbit kidney and lung. Induction of cytochrome P4502E1
      by diabetes was identified by immunochemical detection on Western blots in the
      lung and kidney microsomes of rabbits. In parallel to CYP2E1 induction, aniline 4
      hydroxylase and p-nitrophenol hydroxylase activities were markedly increased in
      diabetic rabbit lung and kidney. CYP2B4 and CYP2E1 dependent drug metabolism did
      not show any tissue variation in diabetic rabbit. These findings are in contrast
      to those of rats, mice and hamster. The results of the present work, in
      combination with those of the previous work [Arinc, E., Arslan, S., Adali, O.,
      2005. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and
      associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol.
      79, 427-433], indicate the existence of species-dependent response of CYP
      dependent drug metabolizing enzymes to diabetes. A procarcinogen and food
      contaminant, N-nitrosodimethylamine (NDMA), is converted to its carcinogenic form
      after it is activated with NDMA N-demethylase. In the current study, a
      statistically significant increase of liver, kidney and lung NDMA N-demethylase
      activity associated with CYP2E1 was shown in diabetic rabbit. Thus, it is
      expected that, the risk of nitrosamine induced carcinogenesis will be greater in
      liver, kidney and lung of the diabetic subjects.

PMID- 17034925
TI  - Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese
      medaka (Oryzias latipes) cells.
AB  - The Japanese medaka (Oryzias latipes) has been used to investigate diverse
      aspects of toxicology, genetics and developmental biology and to monitor
      biological changes caused by endocrine disruptors. In this study, we analyzed a
      medaka homolog of human DJ-1 (meDJ-1) in cultured medaka cells into which
      nonylphenol (NP) was added. Like human DJ-1, meDJ-1 was found to be oxidized by
      treatment with H(2)O(2) and its pI was shifted to acidic points. NP was found to
      induce cell death with kinetics similar to that of H(2)O(2) in cultured medaka
      OLHE-13 cells. After OLHE-13 cells had been treated with sub-lethal
      concentrations of H(2)O(2) and NP, production of reactive oxygen species and
      oxidation of meDJ-1 were observed. meDJ-1 knockdown by short interfering RNA
      rendered OLHE-13 cells susceptible to H(2)O(2) and NP-induced cell death,
      suggesting a protective role of DJ-1 against oxidative stress-induced cell death
      in medaka cells. These results suggest that meDJ-1 is a suitable biomarker for
      oxidative stress reactions in medaka.

PMID- 17034924
TI  - A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal
      tract.
AB  - Groups of Fischer 344 rats (20/sex/group) received control or treated diets at
      levels of 0, 25,000 or 50,000 ppm kappa carrageenan with a molecular weight range
      (Mw) of 196,000-257,000 Da for 90 days. The Low Molecular Weight Tail (LMT)
      ranged between 1.9% and 12.0%<50 kDa (mean 7%) based on the results of a program
      initiated to develop a validated analytical method to measure the LMT. This is
      the first GLP dietary study in which carrageenan is characterized by percentage
      LMT. Clinical examinations were performed daily. Individual food consumption/body
      weight measurements were made weekly. Ophthalmic exam was conducted prior to and
      at the end of treatment. Hematology/serum chemistry and urinalysis evaluations
      were done at necropsy, as were organ weight determinations for adrenals, brain,
      heart, kidneys, liver, ovaries, spleen, testes and thyroid with parathyroids.
      Full histopathological evaluation of organs was conducted on the control and
      50,000 ppm groups, including hematoxylin-eosin-stained cross sections of paraffin
      embedded rolled colon. Clinical signs were limited to soft feces in high dose
      rats and to a lesser extent in low dose rats. There were no treatment-related
      effects on body weights, urinalysis, hematology or clinical chemistry parameters,
      or on organ weights or ophthalmic, macroscopic or microscopic findings. The
      gastrointestinal tract appeared normal in detailed histopathological evaluation
      using the Swiss roll technique. The NOAEL is 50,000 ppm in the diet (mean
      calculated test material consumption of 3394+/-706 mg/kg/day in males, 3867+/-647
      mg/kg/day in females). The results of the study provide evidence that it is not
      necessary to characterize carrageenan by a specification for LMT (less than 5%
      below 50 kDa) as has been done in Commission Directive 2004/45/EC of 16 April
      2004 (Commission Directive, 2004/45/EC of 16 April 2004 amending Directive
      96/77/EC laying down specific purity criteria on food additives other than colors
      and sweeteners. Official Journal of European Union 20 April, 2004, L113/19
      L113/21).

PMID- 17034927
TI  - His164 regulates accessibility to the active site in fungal 17beta-hydroxysteroid
      dehydrogenase.
AB  - 17beta-Hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta
      HSDcl) is an NADPH-dependent member of the short-chain dehydrogenase/ reductase
      superfamily. To study the catalytic properties of this enzyme, we prepared
      several specific mutations of 17beta-HSDcl (Tyr167Phe, His164Trp/Gly, Tyr212Ala).
      Wild-type 17beta-HSDcl and the 17beta-HSDcl mutants were evaluated by
      chromatographic, kinetic and thermodynamic means. The Tyr167Phe mutation resulted
      in a complete loss of enzyme activity, while substitution of His164 with Trp and
      Gly both resulted in higher specificity number (V/K) for the steroid substrates,
      which are mainly a consequence of easier accessibility of steroid substrates to
      the active-site hollow under optimized conditions. The Tyr212Ala mutant showed
      increased activity in the oxidative direction, which appears to be a consequence
      of increased NADPH dissociation. The kinetic characterizations and thermodynamic
      analyses also suggest that His164 and Tyr212 in 17beta-HSDcl have a role in the
      opening and closing of the active site of this enzyme and in the discrimination
      between oxidized and reduced coenzyme.

PMID- 17034926
TI  - Class II composite restorations with metallic and translucent matrices: 2-year
      follow-up findings.
AB  - OBJECTIVE: The aim of this randomized, clinical study was to evaluate the
      performance of composite restorations placed with two matrix and wedge systems
      after a 2-year follow-up. METHODS: Twenty-three patients were selected, and
      received at least two Class II restorations, one with metallic matrix and wooden
      wedge and other with polyester matrix and reflective wedge. One dentist placed
      all the 109 restorations. All cavities were restored using Single Bond and P-60
      (3M ESPE), according to manufacturer's instructions. In the metal matrix group,
      polymerization was performed from occlusal, and in the polyester group, through
      the reflective wedge. Restorations were evaluated at baseline and after 12 and 24
      months by the modified USPHS criteria, and data were analyzed with Mann-Whitney
      and Wilcoxon Signed Rank tests (alpha=0.05). RESULTS: Fifteen subjects and 78
      restorations were re-evaluated after 24 months. A significant decrease in the
      quality of cervical adaptation and proximal contacts by radiographic evaluation
      was evidenced (p<0.05), but no differences between the two matrix systems were
      detected (p>0.05). In the clinical evaluation there were no significant
      differences between matrices after 2 years (p>0.05). A compromising of marginal
      adaptation, marginal staining and proximal contacts aspects for both matrix
      systems was evidenced, and restorations placed with translucent matrices showed
      loss of color stability (p<0.05). CONCLUSIONS: Whereas restorations presented
      some clinical aspects somewhat compromised after 2 years, the matrix and wedge
      systems evaluated showed similar clinical performance.

PMID- 17034929
TI  - Comment on "Human papillomavirus in the oral mucosa of women with genital human
      papillomavirus lesions" [Eur. J. Obstet. Gynecol. Reprod. Biol. 126 (2006) 104
      106].

PMID- 17034928
TI  - Respiratory sinus arrhythmia and diseases of aging: obesity, diabetes mellitus,
      and hypertension.
AB  - Associations between respiratory sinus arrhythmia (RSA) and several chronic
      diseases, including obesity, diabetes mellitus, and hypertension, have been
      documented in recent years. Although most evidence suggests reduced RSA is the
      result of chronic disease rather than the cause, some studies have documented
      reduced RSA among at-risk individuals prior to disease onset. These results raise
      the possibility that decreased vagal tone may play a role in the pathogenesis of
      certain chronic diseases. Presented here is a brief overview of studies which
      examine the relationship between vagal tone, as measured by RSA and baroreflex
      gain, and diseases of aging, including obesity, diabetes mellitus, and
      hypertension. Mechanisms by which vagal tone may be related to disease processes
      are discussed. In addition, we present results from a population-based study of
      RSA and hypertension in older adults. Consistent with previous studies, we found
      an inverse relationship between RSA and age, cigarette use, and diabetes. In
      logistic regression models which control for age, cigarette use, and diabetes, we
      found RSA was a significant negative predictor of hypertension. We conclude that
      the relationship between RSA and hypertension is somewhat independent of the age
      related decline in parasympathetic activity.

PMID- 17034930
TI  - An integrated approach to modeling resource utilization for rural communities in
      developing countries.
AB  - Resource consumption in developing countries has been the focus of a considerable
      amount of research. What has been understudied however, has been the feedback
      affects of resource consumption on resource availability to both households and
      communities. Heavy reliance on natural resources and intensive smallholder
      agriculture common to many rural communities in developing countries has forced
      people to fulfill short-term needs to the detriment of long-term ecological and
      livelihood sustainability. This paper introduces a conceptual framework to
      examine how individuals and households fulfill daily caloric needs and the
      aggregate effects on resource availability and consumption. Data were collected
      from a large number of published case studies of rural land-use dynamics, growth
      and yield models, and human livelihoods were reviewed from scientific journals,
      reports published by NGOs, and government reports. Using inputs defined by the
      user, the model tracks annual fuelwood and agricultural land use based on meeting
      individual energy demands. A case-study-based analysis was patterned after
      smallholder agriculturalists at the family and community level. Three scenarios
      are presented in this paper using data from Uganda to illustrate the application
      of this model.

PMID- 17034931
TI  - Testosterone and prostate cancer.

PMID- 17034932
TI  - Relationship between vascular damage degrees and endothelial progenitor cells in
      patients with erectile dysfunction: effect of vardenafil administration and PDE5
      expression in the bone marrow.
AB  - OBJECTIVES: To evaluate the levels of circulating progenitor cells (PCs) and the
      effect of a single dose of vardenafil 20mg on the number of these cells in men
      with erectile dysfunction (ED) and various degree of vascular injury at the
      carotid artery level. METHODS: Sixty-eight patients with ED and various degree of
      carotid damage, and 25 controls were enrolled. Patients were divided into three
      groups according to their intima media thickness (IMT) status (normal, mild
      increase, or plaque). All subjects received vardenafil 20mg, and evaluation of
      the number of circulating PCs was performed at baseline and 4h after vardenafil
      administration. An RNA expression analysis of phosphodiesterase type 5 (PDE5) on
      bone marrow was also performed. RESULTS: We found a significant reduction of
      circulating PCs in ED patients with respect to controls and a reduction in PC
      counts in patients with mild IMT increase or plaque, but not in those with normal
      IMT. Four hours after vardenafil administration we observed an increase in the
      number of PCs in all patients and controls. Reverse transcriptase-polymerase
      chain reaction analysis showed that human bone marrow expresses PDE5 messenger
      RNA. CONCLUSIONS: Patients with ED and a low number of circulating PCs may be
      considered at increased risk for an endothelial dysfunction. An impaired response
      to vardenafil stimulus may be proposed as a surrogate marker of a patient's
      endothelial regenerative ability.

PMID- 17034933
TI  - The prostate cancer prevention trial and its messages.

PMID- 17034934
TI  - From membranes to systems: self-configuration and self-replication in membrane
      systems.
AB  - Membrane systems are purely abstract computational models afar inspired by
      biological cells, their membranes, and their biochemistry. The inherently
      parallel nature of membrane systems makes them obviously highly inefficient to
      execute on a sequential von Neumann computer architecture and in addition,
      programming a membrane system is often a painstakingly difficult undertaking. The
      main goal of this paper is to provide some key elements for bringing membrane
      systems from the abstract model closer to a genuine, novel, and unconventional in
      silico computer architecture. In particular, we will address the mechanisms of
      self-configuration and self-replication on a macroscopic level and will discuss
      some general issues related to genuine hardware realizations on the microscopic
      level.

PMID- 17034935
TI  - Directional hearing in a silicon cricket.
AB  - Phonotaxis is the ability to orient towards or away from sound sources. Crickets
      can locate conspecifics by phonotaxis to the calling (mating) song they produce,
      and can evade bats by negative phonotaxis from echolocation calls. The behaviour
      and underlying physiology have been studied in some depth, and the auditory
      system solves this complex problem in a unique manner. Experiments conducted on a
      simulation model of the system indicated that the mechanism output a directional
      signal to sounds ahead at calling song frequency and to sounds behind at
      echolocation frequencies. We suggest that this combination of responses helps
      simplify later processing in the cricket. To further explore this result, an
      analogue, very large scale integrated (aVLSI) circuit model of the mechanism was
      designed and built; results from testing this agreed with the simulation. The
      aVLSI circuit was used to test a further hypothesis about the potential
      advantages of the positioning of the acoustic inputs for sound localisation
      during walking. There was no clear advantage to the directionality of the system
      in their location. The aVLSI circuitry is now being extended to use on a robot
      along with previously modelled neural circuitry to better understand the complete
      sensorimotor pathway.

PMID- 17034936
TI  - Landfill leachate treatment with ozone and ozone/hydrogen peroxide systems.
AB  - In the search for an efficient and economical method to treat a leachate
      generated from a controlled municipal solid waste landfill site (Jebel Chakir) in
      the region of greater Tunis in Tunisia, ozone alone and ozone combined with
      hydrogen peroxide were studied. The leachate was characterised by high COD, low
      biodegradability and intense dark colour. A purpose-built reactor, to avoid
      foaming, was used for the study. It was found that ozone efficacy was almost
      doubled when combined with hydrogen peroxide at 2g/L but higher H(2)O(2)
      concentrations gave lower performances. Enhancement in the leachate
      biodegradability from about 0.1 to about 0.7 was achieved by the O(3)/H(2)O(2)
      system. Insignificant changes in pH that may due to buffering effect of
      bicarbonate was found. A small decrease in sulphate concentrations were also
      observed. In contrast, chloride concentration declined at the beginning of the
      experiment then increased to reach its initial value. Estimates of the operating
      costs were made for comparison purposes and it was found that the O(3)/H(2)O(2)
      system at 2g/L H(2)O(2) gave the lowest cost of about 3.1TND( approximately
      2.3USD)/kgCOD removed.

PMID- 17034937
TI  - Application of Fenton oxidation to cosmetic wastewaters treatment.
AB  - The removal of organic matter (TOC and COD) from a cosmetic wastewater by Fenton
      oxidation treatment has been evaluated. The operating conditions (temperature as
      well as ferrous ion and hydrogen peroxide dosage) have been optimized. Working at
      an initial pH equal to 3.0, a Fe(2+) concentration of 200 mg/L and a H(2)O(2)
      concentration to COD initial weight ratio corresponding to the theoretical
      stoichiometric value (2.12), a TOC conversion higher than 45% at 25 degrees C and
      60% at 50 degrees C was achieved. Application of the Fenton oxidation process
      allows to reach the COD regional limit for industrial wastewaters discharges to
      the municipal sewer system. A simple kinetic analysis based on TOC was carried
      out. A second-order equation describes well the overall kinetics of the process
      within a wide TOC conversion range covering up to the 80-90% of the maximum
      achievable conversion.

PMID- 17034938
TI  - The effect of Fe0/Fe2+/Fe3+ on nitrobenzene degradation in the anaerobic sludge.
AB  - The influence of Fe(0)/Fe(2+)/Fe(3+) on the nitrobenzene (NB) degradation in the
      anaerobic granular sludge was studied and the results demonstrated that: adding
      iron powder into the anaerobic sludge could exert an accelerative effect on the
      NB degradation and the degradation rate was faster than that by using iron or the
      anaerobic sludge alone. The external addition of Fe(2+)/Fe(3+) exhibited
      different influences on the NB degradation depending on the concentrations of
      Fe(2+)/Fe(3+) and the solution's pH. When Fe(2+)/Fe(3+) are less than 100 mg/L at
      pH 6, Fe(2+)/Fe(3+) inhibited the NB degradation slightly, and when Fe(2+)/Fe(3+)
      was 100-200 mg/L, the NB degradation was enhanced. When pH was shifted to 9,
      Fe(2+) of lower than 100 mg/L promoted the NB degradation, and 200 mg/L Fe(2+)
      inhibit the NB degradation. The synergism of combined use of iron and the
      anaerobic sludge in treating NB wastewater was proposed, and adjusting the
      concentrations of Fe(2+)/Fe(3+) in the anaerobic sludge according to the pH of
      the wastewater could be an effective method to obtain a high removal rate of NB.

PMID- 17034939
TI  - Mathematical modelling of 4-chlorophenol inhibition on COD and 4-chlorophenol
      removals in an activated sludge unit.
AB  - A mathematical model was developed for an activated sludge unit treating 4
      chlorophenol (4-CP) containing synthetic wastewater composed of diluted molasses,
      urea, KH(2)PO(4) and MgSO(4) with COD and 4-CP contents of 2500 and 500 mg l(-1),
      respectively. The model included 4-CP inhibition on COD and 4-CP removals.
      Experimental data obtained at different hydraulic residence times (HRT=5-30h) and
      sludge ages (SRT, 3-30 days) were used to estimate the kinetic and inhibition
      constants for COD and 4-CP removal rates. 4-CP inhibition on COD removal was
      negligible while the inhibition on 4-CP removal was significant. The specific
      rate constant (k), saturation constant (K(s)) for COD oxidation were found to be
      2.64 day(-1) and 559 mg l(-1), respectively. A similar model was used for 4-CP
      oxidation in the activated sludge unit and the constants were found to be k'=1.44
      day(-1), K'(s)=25.7 mgl(-1), K"(CP)=559 mg l(-1),and K(I,CP)=17 mg l(-1).
      Increases in death rate constant because of 4-CP inhibition was also quantified
      and the inhibition constants were determined for both COD and 4-CP removals.
      Model predictions with the estimated kinetic constants were in good agreement
      with the experimental data. Developed model can be used to estimate the
      performance of an activated sludge unit treating 4-CP containing wastewater under
      the specified experimental conditions.

PMID- 17034940
TI  - Studies on the sorption of praseodymium (III), holmium (III) and cobalt (II) from
      nitrate medium using TVEX-PHOR resin.
AB  - The use of TVEX-PHOR resin for the sorption of praseodymium (III), holmium (III)
      and cobalt (II) from nitrate medium was carried out using batch and column
      techniques. Various parameters affecting the uptake of these metal ions such as
      v/m ratio, pH and the metal ion concentration were separately studied. Effect of
      temperature on the equilibrium distribution values has been studied to evaluate
      the changes in standard thermodynamic quantities. Experimental results of the
      investigated metal ions were found to fit to Freundlich isotherm model over the
      entire studied concentration range. Selectivity sequence of the resin for these
      metals is Ho>Pr>Co. The recovery of the investigated metals from the loaded resin
      is preformed with 0.1M sulphuric acid.

PMID- 17034941
TI  - Development of a miniature calorimeter for identification and detection of
      explosives and other energetic compounds.
AB  - The development of versatile systems capable of providing rapid, portable, and
      inexpensive detection of explosives and energetic compounds are critically needed
      to offer enhanced levels of protection against current and future threats to
      homeland security, as well as satisfying a wide range of applications in the
      fields of forensic analysis, emergency response, and industrial hazards analysis.
      Calorimetric techniques have been largely overlooked in efforts to develop
      advanced chemical analysis technology, largely because of limitations associated
      with the physical size of the instruments and the relatively long timescales (>30
      min) required to obtain a result. This miniaturized calorimeter circumvents these
      limitations, thereby creating a first-of-its-kind system allowing thermal
      analysis to be performed in a portable format that can be configured for use in a
      variety of field operations with a significantly reduced response time
      (approximately 2 min). Unlike current explosives detectors, this system is based
      on calorimetric techniques that are inherently capable of providing direct
      measurements of energy release potential and therefore do not depend on prior
      knowledge of familiar compounds.

PMID- 17034942
TI  - Occurrence of disinfection by-products in low DOC surface waters in Turkey.
AB  - A total of 29 surface waters from different regions of Turkey were sampled once a
      month during 2004. Filtered raw water samples were characterized, chlorinated and
      the concentrations of disinfection by-products (DBPs) were measured. All waters
      were low in DOC ranging from 0.91 to 4.42 mg/L. The range of annual average
      trihalomethanes (THMs) and haloacetic acids (HAAs) concentrations in all waters
      was 21-189 and 18-149mug/L, respectively. Total mass contributions of halides in
      THMs and HAAs to absorbable organic halides (AOX) ranged between 10 and 56% in
      all waters on annual average basis, indicating that significant amounts of other
      DBPs are being formed in the majority of the tested waters. A strong linear
      correlation was obtained between the concentrations of THMs and HAAs. Rather poor
      correlations were found for THMs-AOX and HAAs-AOX levels. For both THMs and HAAs,
      chlorinated species dominated over brominated ones since the majority of water
      sources had very low bromide levels. While chloroform and trichloroacetic acid
      were the major THM and HAA compounds, respectively; the extent of formation and
      speciation of DBPs varied greatly by season and water source. No consistent
      general trends were observed in terms of seasonal variations in DBP levels,
      suggesting that the characteristics of NOM moieties and their chlorine reactivity
      vary by season in almost all waters tested.

PMID- 17034943
TI  - Synthesis and heavy metal immobilization behaviors of slag based geopolymer.
AB  - In this paper, two aspects of studies are carried out: (1) synthesis of
      geopolymer by using slag and metakaolin; (2) immobilization behaviors of slag
      based geopolymer in a presence of Pb and Cu ions. As for the synthesis of slag
      based geopolymer, four different slag content (10%, 30%, 50%, 70%) and three
      types of curing regimes (standard curing, steam curing and autoclave curing) are
      investigated to obtain the optimum synthesis condition based on the compressive
      and flexural strength. The testing results showed that geopolymer mortar
      containing 50% slag that is synthesized at steam curing (80 degrees C for 8h),
      exhibits higher mechanical strengths. The compressive and flexural strengths of
      slag based geopolymer mortar are 75.2 MPa and 10.1 MPa, respectively.
      Additionally, Infrared (IR), X-ray diffraction (XRD) and scanning electron
      microscopy (SEM) techniques are used to characterize the microstructure of the
      slag based geopolymer paste. IR spectra show that the absorptive band at 1086 cm(
      1) shifts to lower wave number around 1007 cm(-1), and some six-coordinated Als
      transforms into four-coordination during the synthesis of slag based geopolymer
      paste. The resulting slag based geopolymeric products are X-ray amorphous
      materials. SEM observation shows that it is possible to have geopolymeric gel and
      calcium silicate hydrate (C-S-H) gel forming simultaneously within slag based
      geopolymer paste. As for immobilization of heavy metals, the leaching tests are
      employed to investigate the immobilization behaviors of the slag based geopolymer
      mortar synthesized under the above optimum condition. The leaching tests show
      that slag based geopolymer mortar can effectively immobilize Cu and Pb heavy
      metal ions, and the immobilization efficiency reach 98.5% greater when heavy
      metals are incorporated in the slag geopolymeric matrix in the range of 0.1-0.3%.
      The Pb exhibits better immobilization efficiency than the Cu in the case of large
      dosages of heavy metals.

PMID- 17034944
TI  - Biosorption of Reactive Black 5 dye by Penicillium restrictum: the kinetic study.
AB  - Biosorption of Reactive Black 5 (RB 5) dye onto dried Penicillium restrictum
      biomass was studied with respect to pH, contact time, biosorbent and dye
      concentrations. The effect of temperature on the biosorption efficiency was also
      carried out and the kinetic parameters were determined. Optimum initial pH,
      equilibrium time and biomass concentration for RB 5 dye were found to be 1.0, 75
      min and 0.4 g dm(-3) at 20 degrees C, respectively. The maximum biosorption
      capacities (q(max)) of RB 5 dye onto dried P. restrictum biomass were 98.33 and
      112.50mg (g biomass)(-1) at 175 mg dm(-3) initial dye concentration at 20 and 50
      degrees C, respectively, and it was 142.04 mg (g biomass)(-1) at 200 mg dm(-3)
      initial dye concentration at 35 degrees C. The results indicate that the
      biosorption process obeys a pseudo-second-order kinetic model.

PMID- 17034945
TI  - A distinct group of non-cholinergic neurons along the mid-line of the septum and
      within the rat medial septal nucleus.
AB  - The septum is a critical and integral component of the limbic brain that serves
      as a link between diverse brain structures while being necessary for human
      cognition and emotionality. A major anatomical component of the septum is
      designated as the medial septum/diagonal band of Broca complex (MS/DB). A primary
      focus of much research has been to investigate cholinergic neurons within the
      MS/DB, as these are the rodent brain's main source of acetylcholine to the cortex
      and hippocampus. On the other hand, we have chosen to investigate a specific
      group of neurons that lie on the midline of the MS/DB in an area distinguished
      anatomically as the medial septal nucleus (MSN). Based on somatic morphology and
      electrophysiological characteristics we conclude that these neurons,
      characterized into three different types, are non-cholinergic.

PMID- 17034946
TI  - High frequency of neurexin 1beta signal peptide structural variants in patients
      with autism.
AB  - Neuroligins are postsynaptic membrane cell-adhesion molecules which bind to beta
      neurexins, a family of proteins that act as neuronal cell surface receptors. To
      explore the possibility that structural variants in the beta-neurexin genes
      predispose to autism, the coding regions and associated splice junctions of three
      beta-neurexin genes were scanned with detection of virtually all mutations-SSCP
      (DOVAM-S) in 72 Caucasian patients with autism. In addition, segments of the
      neurexin 1beta gene were sequenced in 131 additional Caucasian and 61 Afro
      American patients with autism from South Carolina and the Midwest. Two putative
      missense structural variants were identified in the neurexin 1beta gene in four
      Caucasian patients with autism and not in 535 healthy Caucasian controls (4/203
      vs. 0/535, P=0.0056). Initial family data suggest that incomplete penetrance may
      occur. In addition, no structural variant was found in the neurexin 2beta gene
      and the neurexin 3beta gene. In the context of all available data, we conclude
      that mutations of the neurexin 1beta gene may contribute to autism
      susceptibility.

PMID- 17034947
TI  - Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density
      array.
AB  - DNA repair systems act to maintain genome integrity in the face of replication
      errors, environmental insults, and the cumulative effects of age. The mRNA
      expressions of 27 genes of the DNA repair system as well as their correlation
      with the clinical characteristics were studied in human astrocytoma. We applied
      TaqMan low-density array to investigate the mRNA expressions of 27 DNA repair
      genes in 40 astrocytoma tissues (10 of grade II, 10 of grade III, and 20 of grade
      IV, according to the WHO Grading System). And the normal brain tissues from 10
      non-astrocytoma patients were collected as the control. In addition, correlation
      of their mRNA levels with clinical characteristics was also analyzed. We found
      that the expression of the 13 genes were significantly (P<0.01) down-regulated in
      grade II, III, IV of astrocytoma compared to normal brain tissues, including
      ERCC1, ERCC2, ERCC3, ERCC4, MGMT, MLH1, MLH3, NTHL1, OGG1, RAD50, SMUG1, XRCC4
      and XRCC5. Meanwhile, we found that the expression of MSH2, MSH6, NUDT1 and XRCC3
      were only significantly lower in grade II and III of astrocytoma, and the
      expression of MRE11A and MUS81 were only significantly lower in grade III and IV.
      But the expression of MPG, MSH3, MUTHY and RAD51 were not changed in any grade of
      astrocytoma. Furthermore, we found that the decrease expression of eight genes
      was significantly (P<0.05) associated with a poor prognosis, including ERCC3,
      ERCC4, MLH3, MRE11A, NTHL1, RAD50, XRCC4 and XRCC5. We suggest that TaqMan low
      density array is an effective multivariate technique to examine the expression of
      DNA repair genes in astrocytomas, which can be applied to identify tumor-specific
      genes. We also suggest that the down-regulation of some DNA repair genes may be
      associated with pathogenesis and poor prognosis of astrocytoma.

PMID- 17034948
TI  - Interhemispheric transfer time and structural properties of the corpus callosum.
AB  - The present study examined how interhemispheric transfer time (IHTT) is affected
      by interindividual differences in corpus callosum (CC) architecture. For this
      purpose the CC of 42 healthy male subjects was assessed by applying a combination
      of morphological and diffusion-tensor magnetic resonance imaging to characterize
      the CC on macro- (midsagittal area) and microstructural level (mean diffusion,
      fractional anisotropy). Following the so-called Poffenberger paradigm, IHTT was
      determined with both reaction time measures and event-related potentials recorded
      in response to stimuli briefly presented to either left or right visual
      hemifield. Statistical analysis revealed significant negative correlations
      between mean diffusion and IHTT estimates derived from the P100 component (at
      O1/O2 electrode pair), particularly in the posterior CC subregion. Interpreting
      mean diffusion as an index of microstructural tissue properties, IHTT appears to
      be directly related to the structural integrity of the posterior CC.

PMID- 17034949
TI  - Fluorescence imaging and investigations of directly labelled chromosomes using
      scanning near-field optical microscopy.
AB  - Scanning near-field optical microscopy (SNOM) has been successfully employed to
      generate high resolution (<100nm) fluorescence images of directly tagged human
      chromosomes. Direct tagging, fluorescence in-situ hybridisation processes (with
      and without amplification) are investigated and their fluorescence response to
      near-field excitation are compared. Using the simultaneous topography mode of
      SNOM, chromosome morphology was seen to differ as a result of the two processes;
      with chromatin collapse more extensive when the amplified direct tagging
      procedure was used. The results are discussed in the context of developing locus
      specific direct tags together with high resolution SNOM imaging for the
      observation of chromosome aberrations.

PMID- 17034950
TI  - Comparison of the activity of selamectin, imidacloprid and fipronil for the
      treatment of cats infested experimentally with Ctenocephalides felis felis and
      Ctenocephalides felis strongylus.
AB  - Twenty adult, domestic short hair cats were randomly allocated into four groups
      of five cats and housed in separated cages. Each cat was infested with 25 fleas
      Ctenocephalides felis felis and 25 Ctenocephalides felis strongylus and 2 days
      later (day 0) the cats in group 1, 2 and 3 received a spot on application of
      selamectin, imidacloprid or fipronil, respectively, while the cats in group four
      were not treated. The cats were combed 48 h later, the fleas were removed,
      counted and their subspecies were determined. All the cats were reinfested with
      the same number of the two subspecies of fleas on days 7, 14, 21, 29 and 35. The
      efficacy of each treatment was calculated 48 h after each infestation. The mean
      number of fleas on the control cats was 16.4 C. f. felis and 13.4 C. f.
      strongylus. The three treatments were effective for the first 31 days for C. f.
      felis and for the full 37 days for C. f. strongylus. Over the first 31 days, the
      efficacy of selamectin ranged from 89 to 100% and 85 to 100% against C. f. felis
      and C. f. strongylus, respectively, the efficacy of imidacloprid ranged from 76
      to 100% and 92 to 100% and the efficacy of fipronil ranged from 98 to 100% and 97
      to 100% against C. f. felis and C. f. strongylus. There were no significant
      differences between the control of C. f. felis and C. f. strongylus by the three
      products.

PMID- 17034951
TI  - Biochemical characterization and molecular cloning of a plasminogen activator
      proteinase (LV-PA) from bushmaster snake venom.
AB  - The protein (LV-PA) from bushmaster (Lachesis muta muta) venom is a serine
      proteinase which specifically activates the inactive proenzyme plasminogen. LV-PA
      is a single chain glycoprotein with an apparent molecular mass of 33 kDa that
      fell to 28 kDa after treatment with N-Glycosidase F (PNGase F). Approximately 93%
      of its protein sequence was determined by automated Edman degradation of various
      fragments derived from a digestion with trypsin. A cDNA library of L. m. muta was
      constructed to generate expressed sequence tags (ESTs) and the plasminogen
      activator precursor cDNA was sequenced. The complete amino acid sequence of the
      enzyme was deduced from the cDNA sequence. LV-PA is composed of 234 residues and
      contains a single asparagine-linked glycosylation site, Asn-X-Ser, bearing sugars
      that account for approximately 10% of the enzyme's total molecular mass of 33
      kDa. The sequence of LV-PA is highly similar to the plasminogen activators (PAs)
      TSV-PA from Trimeresurus stejnegeri venom and Haly-PA from Agkistrodon halys.
      Furthermore, the mature protein sequence of LV-PA exhibits significant similarity
      with other viperidae venom serine proteinases which affect many steps of
      hemostasis, ranging from the blood coagulation cascade to platelet function. The
      Michaelis constant (Km) and the catalytic rate constant (kcat) of LV-PA on four
      chromogenic substrates were obtained from Lineweaver-Burk plots. In addition, we
      used an indirect enzyme-linked immunoabsorbent assay (ELISA) to explore the
      phylogenetic range of immunological cross-reactivity (using antibodies raised
      against LV-PA) with analogous serine proteinases from two viperidae venoms and
      mammals.

PMID- 17034952
TI  - Surgical treatment of oral burn contractures with assistance of external
      distractors: report of two cases.

PMID- 17034953
TI  - Targeted therapy in advanced non-small cell lung cancer (NSCLC): where do we
      stand?
AB  - Cytotoxic chemotherapy has helped improve the outcomes in patients with advanced
      non-small cell lung cancer (NSCLC), but we seem to have reached a plateau with
      respect to the benefit obtained. Also, a large subset of elderly patients and
      those with a poor performance status cannot tolerate these drugs at recommended
      doses. There is a growing need to incorporate newer drugs with different
      mechanisms of action and better safety profile. The epidermal growth factor
      receptor family (EGFR) and vascular endothelial growth factor (VEGF) have been
      identified as potential targets and agents acting specifically against these
      targets have been developed with the hope of improving outcomes. Although recent
      data with the small molecule EGFR tyrosine kinase inhibitors have been
      disappointing, there have been instances of dramatic responses thereby raising
      questions about the ideal patient to whom these drugs should be administered.
      Cetuximab, the anti-EGFR antibody has shown promising results. Bevacizumab, the
      anti-VEGF antibody was the first drug to demonstrate a survival benefit in first
      line treatment when added to chemotherapy. This review will briefly discuss the
      important trials using these targeted agents in advanced NSCLC.

PMID- 17034954
TI  - Oral progesterone decreases saccadic eye velocity and increases sedation in
      women.
AB  - The aim of this study was to investigate the neurophysiological and behavioural
      effects of a single dose of progesterone in women. Allopregnanolone is a
      metabolite of progesterone and a potent positive modulator of the GABA(A)
      receptor and produces sedative and anxiolytic effects. This study was designed to
      examine the effect of oral progesterone and the metabolite allopregnanolone in
      women. Women (n=15) in their follicular phase received oral progesterone (400mg)
      or placebo. Dependent measures included plasma levels of progesterone and
      allopregnanolone, saccadic eye velocity (SEV), subjective ratings (visual
      analogue scales), and reaction time. Administration of progesterone decreased SEV
      and increased sedation. This effect is probably due to enhanced GABA activity.

PMID- 17034956
TI  - Laser iridotomy for intraoperative floppy iris syndrome.

PMID- 17034955
TI  - Prediction of treatment response by HPA-axis and glucocorticoid receptor
      polymorphisms in major depression.
AB  - OBJECTIVE: We investigated whether treatment response is predicted by
      hypothalamus-pituitary-adrenal (HPA) axis parameters, or by genetic polymorphisms
      in the glucocorticoid receptor (GR), that regulates its feedback. METHODS: Ninety
      eight outpatients completed 8 weeks of paroxetine treatment. Treatment response
      was defined as a 50% decrease in Hamilton Rating Scale for depression (HRSD)
      ratings. At baseline, 24h urinary cortisol excretion, and cortisol and ACTH
      concentrations in a DEX/CRH test were measured. The presence of polymorphisms in
      the GR DNA sequence (BclI, ER22/23EK, N363S) was determined. Prediction of
      treatment response was analysed by calculating response rates per tertile of an
      HPA-axis parameter and per GR genotype. RESULTS: The response rate in the high
      ACTH tertile was significantly lower as compared to the intermediate tertile, but
      not compared to the low tertile (response rates from high to low tertile: 33%,
      67% and 42%). Carriers of the BclI polymorphism had higher ACTH values than non
      carriers (baseline ACTH: 3 versus 5ng/l, p=0.02) and showed a trend towards lower
      decrease of HRSD rates than non-carriers (HRSD decrease: 8 versus 11,
      respectively, p=0.07). In a subgroup of BclI carriers, patients in the high ACTH
      tertile had a lower decrease in HRSD and lower response rates than patients in
      the low ACTH tertiles (HRSD decrease from high to low tertile: 5, 9 and 11,
      p<0.01). CONCLUSION: The results suggest that hyperactivity of the HPA-axis
      predict worse treatment outcome. The BclI polymorphism explains, in part, DEX/CRH
      test results and tends to be associated with worse treatment outcome.

PMID- 17034957
TI  - Cytohistopathologic hybrid renal cell carcinoma with papillary and clear cell
      features.
AB  - Clear cell (CRCC) and papillary (PRCC) renal cell carcinomas (RCC) are the two
      most frequent subtypes of RCC. In this study, we studied RCC which displayed a
      hybrid morphology with areas of PRCC and CRCC or which contained papillary
      structures with clear cell changes (CCC). Consecutive cases of RCC collected over
      a 12-year period were reviewed to identify RCC with papillary structures and a
      possible admixture between CRCC and non-oncocytic PRCC. Special stains for
      glycogen and immunostaining for cytokeratin 7 were applied to sections containing
      both areas of classical PRCC and PRCC with CCC. Of the total of 541 RCC
      retrieved, there were 68 non-oncocytic RCC having papillary structures that could
      be grouped into: (a) group 1 (15 cases), CRCC with areas of papillary formation;
      (b) group 2a (9 cases), PRCC with extensive CCC with areas of foamy epithelial
      cells or macrophages; (c) group 2b (18 cases), RCC with areas of classical PRCC
      with focal CCC; and (d) group 3 (26 cases), RCC with features of groups 2a and 2b
      and containing areas of classical CRCC. There was a high rate (12/68) of
      sarcomatous transformation in the study cases. Groups 2 and 3 were associated
      with a higher rate of vascular invasion, distant metastasis, and mortality than
      classical PRCC and a higher rate of lymph node metastasis than CRCC. Our study
      identifies two groups of RCC (referred to as groups 2 and 3) that exhibit
      characteristic cytohistopathologic hybrid features that set them apart from
      classical RCC. This type of hybrid tumor seems to be associated with a more
      aggressive biologic behavior, and its recognition may facilitate the
      classification of RCC with ambiguous morphology.

PMID- 17034958
TI  - The behavioral economics of will in recovery from addiction.
AB  - Behavioral economic studies demonstrate that rewards are discounted
      proportionally with their delay (hyperbolic discounting). Hyperbolic discounting
      implies temporary preference for smaller rewards when they are imminent, and this
      concept has been widely considered by researchers interested in the causes of
      addictive behavior. Far less consideration has been given to the fact that
      systematic preference reversal also predicts various self-control phenomena,
      which may also be analyzed from a behavioral economic perspective. Here we
      summarize self-control phenomena predicted by hyperbolic discounting,
      particularly with application to the field of addiction. Of greatest interest is
      the phenomenon of choice bundling, an increase in motivation to wait for delayed
      rewards that can be expected to result from making choices in whole categories.
      Specifically, when a person's expectations about her own future behavior are
      conditional upon her current behavior, the value of these expectations is added
      to the contingencies for the current behavior, resulting in reduced impulsivity.
      Hyperbolic discounting provides a bottom-up basis for the intuitive learning of
      choice bundling, the properties of which match common descriptions of willpower.
      We suggest that the bundling effect can also be discerned in the advice of 12
      step programs.

PMID- 17034959
TI  - Newly established in vitro system with fluorescent proteins shows that abnormal
      expression of downstream prion protein-like protein in mice is probably due to
      functional disconnection between splicing and 3' formation of prion protein pre
      mRNA.
AB  - We and others previously showed that, in some lines of prion protein (PrP)
      knockout mice, the downstream PrP-like protein (PrPLP/Dpl) was abnormally
      expressed in brains partly due to impaired cleavage/polyadenylation of the
      residual PrP promoter-driven pre-mRNA despite the presence of a poly(A) signal.
      In this study, we newly established an in vitro transient transfection system in
      which abnormal expression of PrPLP/Dpl can be visualized by expression of the
      green fluorescence protein, EGFP, in cultured cells. No EGFP was detected in
      cells transfected by a vector carrying a PrP genomic fragment including the
      region targeted in the knockout mice intact upstream of the PrPLP/Dpl gene. In
      contrast, deletion of the targeted region from the vector caused expression of
      EGFP. By employing this system with other vectors carrying various deletions or
      point mutations in the targeted region, we identified that disruption of the
      splicing elements in the PrP terminal intron caused the expression of EGFP.
      Recent lines of evidence indicate that terminal intron splicing and
      cleavage/polyadenylation of pre-mRNA are functionally linked to each other. Taken
      together, our newly established system shows that the abnormal expression of
      PrPLP/Dpl in PrP-knockout mice caused by the impaired cleavage/polyadenylation of
      the PrP promoter-driven pre-mRNA is due to the functional dissociation between
      the pre-mRNA machineries, in particular those of cleavage/polyadenylation and
      splicing. Our newly established in vitro system, in which the functional
      dissociation between the pre-mRNA machineries can be visualized by EGFP green
      fluorescence, may be useful for studies of the functional connection of pre-mRNA
      machineries.

PMID- 17034960
TI  - Mavericks, a novel class of giant transposable elements widespread in eukaryotes
      and related to DNA viruses.
AB  - We previously identified a group of atypical mobile elements designated Mavericks
      from the nematodes Caenorhabditis elegans and C. briggsae and the zebrafish Danio
      rerio. Here we present the results of comprehensive database searches of the
      genome sequences available, which reveal that Mavericks are widespread in
      invertebrates and non-mammalian vertebrates but show a patchy distribution in non
      animal species, being present in the fungi Glomus intraradices and Phakopsora
      pachyrhizi and in several single-celled eukaryotes such as the ciliate
      Tetrahymena thermophila, the stramenopile Phytophthora infestans and the
      trichomonad Trichomonas vaginalis, but not detectable in plants. This
      distribution, together with comparative and phylogenetic analyses of Maverick
      encoded proteins, is suggestive of an ancient origin of these elements in
      eukaryotes followed by lineage-specific losses and/or recurrent episodes of
      horizontal transmission. In addition, we report that Maverick elements have
      amplified recently to high copy numbers in T. vaginalis where they now occupy as
      much as 30% of the genome. Sequence analysis confirms that most Mavericks encode
      a retroviral-like integrase, but lack other open reading frames typically found
      in retroelements. Nevertheless, the length and conservation of the target site
      duplication created upon Maverick insertion (5- or 6-bp) is consistent with a
      role of the integrase-like protein in the integration of a double-stranded DNA
      transposition intermediate. Mavericks also display long terminal-inverted repeats
      but do not contain ORFs similar to proteins encoded by DNA transposons. Instead,
      Mavericks encode a conserved set of 5 to 9 genes (in addition to the integrase)
      that are predicted to encode proteins with homology to replication and packaging
      proteins of some bacteriophages and diverse eukaryotic double-stranded DNA
      viruses, including a DNA polymerase B homolog and putative capsid proteins. Based
      on these and other structural similarities, we speculate that Mavericks represent
      an evolutionary missing link between seemingly disparate invasive DNA elements
      that include bacteriophages, adenoviruses and eukaryotic linear plasmids.

PMID- 17034961
TI  - Identification and characterization of novel polymorphic LINE-1 insertions
      through comparison of two human genome sequence assemblies.
AB  - Mobile elements represent a relatively new class of markers for the study of
      human evolution. Long interspersed elements (LINEs) belong to a group of
      retrotransposons comprising approximately 21% of the human genome. Young LINE-1
      (L1) elements that have integrated recently into the human genome can be
      polymorphic for insertion presence/absence in different human populations at
      particular chromosomal locations. To identify putative novel L1 insertion
      polymorphisms, we computationally compared two draft assemblies of the whole
      human genome (Public and Celera Human Genome assemblies). We identified a total
      of 148 potential polymorphic L1 insertion loci, among which 73 were candidates
      for novel polymorphic loci. Based on additional analyses we selected 34 loci for
      further experimental studies. PCR-based assays and DNA sequence analysis were
      performed for these 34 loci in 80 unrelated individuals from four diverse human
      populations: African-American, Asian, Caucasian, and South American. All but two
      of the selected loci were confirmed as polymorphic in our human population panel.
      Approximately 47% of the analyzed loci integrated into other repetitive elements,
      most commonly older L1s. One of the insertions was accompanied by a BC200
      sequence. Collectively, these mobile elements represent a valuable source of
      genomic polymorphism for the study of human population genetics. Our results also
      suggest that the exhaustive identification of L1 insertion polymorphisms is far
      from complete, and new whole genome sequences are valuable sources for finding
      novel retrotransposon insertion polymorphisms.

PMID- 17034962
TI  - A systematic analysis of lineage-specific evolution in metabolic pathways.
AB  - In a search for the lineage-specific evolution of pathways between human,
      chimpanzee, mouse, and rat, orthologous gene families were generated from genome
      sequences. For each family, a model-based ratio of nonsynonymous to synonymous
      nucleotide substitution rates was calculated. Where the free-ratio model of
      individual ratios on each branch was supported, these families were mapped to two
      databases of metabolic pathways (KEGG and BioCyc) and the lineage-specific
      evolution of pathways was evaluated. The most similar pathway evolution was seen
      between mouse and rat, while the evolutionary pattern between human and
      chimpanzee was less correlated. Individual pathways in the human lineage were
      observed to evolve in a faster, lineage-specific manner, including the pathway
      involving arachidonic acid metabolism (identified through the KEGG analysis) and
      pyrimidine metabolism (identified through both analyses).

PMID- 17034963
TI  - Antimicrobial resistance in Salmonella enterica serovar Dublin isolates from beef
      and dairy sources.
AB  - Salmonella enterica serovar Dublin (S. Dublin) is a cattle-adapted Salmonella
      serovar, so if antimicrobial resistance in S. Dublin arises as a result of
      antimicrobial use this most likely occurs within the cattle reservoir without
      impact from antimicrobial use in humans. We tested the antimicrobial resistance
      of bovine-origin S. Dublin isolates from 1986 through 2004 using a standard disk
      diffusion method. High proportions of isolates throughout the time period were
      resistant to one or more antimicrobials, and a marked increase in resistance to
      ceftazidime occurred between 2000 and 2004. Dairy-origin isolates were more
      likely to be resistant to several antibiotics than were isolates from beef
      operations where exposure to antimicrobials is likely to be less frequent.
      Plasmid analysis of a subset of isolates also supported the hypothesis that
      antimicrobial resistance traits in the cattle-adapted serovar Dublin were
      acquired within the bovine host environment.

PMID- 17034964
TI  - Differentially expressed transcripts in shell glands from low and high egg
      production strains of chickens using cDNA microarrays.
AB  - We have constructed a tissue-specific in-house cDNA microarray to identify
      differentially expressed transcripts in shell glands from low (B) and high (L2)
      egg production strains of Taiwanese country chickens during their egg-laying
      period. The shell gland cDNA library was constructed from the high egg production
      strain. cDNA clones (7680) were randomly selected and their 5'-end sequences
      characterized. After excluding overlapping sequences, an in-house cDNA
      microarray, representing 2743 non-redundant transcripts, was generated for
      functional genomic studies. Using our microarray, we have successfully identified
      85 differentially expressed transcripts from the two different strains of chicken
      shell glands. In this study, 34 of these transcripts were associated with signal
      transduction, protein biosynthesis, cell adhesion, cellular metabolism, skeletal
      development, cell organization and biogenesis. We selected a number of the
      differentially expressed transcripts for further validation using semi
      quantitative RT-PCR. These included elongation factor 2 (EEF2), ovocalyxin-32
      (OCX-32) and annexin A2 (ANXA2) which were expressed at high levels in the
      chicken shell glands of the B strain and, in contrast, the coactosin-like protein
      (COTL1), transcription factor SOX18 and MX protein were more highly expressed in
      the L2 strain. Our results suggest that these differentially expressed
      transcripts may be suitable to use as molecular markers for high rates of egg
      production, and now need to be investigated further to assess whether they can be
      applied for use in breeding selection programs in Taiwanese country chickens.

PMID- 17034965
TI  - Characterization of galactose-binding proteins in equine testis and spermatozoa.
AB  - Carbohydrate-binding proteins are thought to be involved in a myriad of sperm
      functions including sperm-oviductal and sperm-zona interactions. Recent studies
      in our laboratory have characterized galactose-binding proteins on equine
      spermatozoa as possible candidate molecules for sperm adhesion to oviduct
      epithelial cells. In the current study, equine sperm membrane proteins were
      subjected to galactose-affinity chromatography, and bound proteins were eluted
      with excess galactose in a calcium-free buffer. The eluted fraction recovered
      after galactose-affinity chromatography was used for generation of a polyclonal
      antibody which was immobilized on an affinity column to recover a purified
      protein from equine sperm extracts. Several protein bands of approximately 70,
      25, and 20-18 kDa were detected with a major band at 25k Da on immunoblots which
      was subjected to N-terminal amino acid sequencing. These galactose binding
      proteins (GBP) were specific to sperm and testis and were absent in all the
      somatic tissues tested. Based upon immunocytochemistry, GBP were localized over
      the sperm head. In noncapacitated sperm, fluorescent labeling was observed over
      the rostral sperm head as well as the postacrosomal area; whereas in capacitated
      sperm, the labeling was localized primarily in the equatorial segment.
      Immunohistochemistry of equine testis demonstrated abundant staining in the
      adluminal region of the seminiferous tubules corresponding to round spermatids.
      In summary, this study demonstrates the presence of testis- and sperm-specific
      galactose binding proteins in the horse. The function of these proteins remains
      to be determined.

PMID- 17034966
TI  - Benefits and risks of long-term low-dose oral continuous combined hormone
      therapy.
AB  - OBJECTIVES: Current recommendations for hormone therapy (HT) are mainly based on
      findings from studies using standard dose regimens in older women who had a
      different health profile from those who start HT soon after the onset of
      menopause. METHODS: We, therefore, reviewed controlled trials assessing the
      efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT)
      started for treatment of climacteric symptoms. This review is limited to oral cc
      HT regimens over sequential regimens as most postmenopausal women prefer not to
      have a return of uterine bleeding, and to studies of at least 2 years in
      duration. RESULTS: Low-dose cc-HT is effective in alleviating climacteric
      symptoms and in maintaining bone density over prolonged periods, although no data
      were available regarding fracture risk. No increased risk of coronary heart
      disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was
      reported in the long-term studies and no definitive evidence for an increased
      risk of breast cancer was found. Breakthrough bleeding during the first months of
      use is less common than with standard dose HT and amenorrhoea is achieved in most
      women over time. These regimens are safe for the endometrium and are well
      tolerated, with a low incidence of adverse events compared with standard doses.
      CONCLUSIONS: Current evidence from controlled trials indicates that low-dose oral
      cc-HT appears effective and safe. This makes it a good choice for the alleviation
      of climacteric symptoms, and for this purpose long-term administration of low
      dose cc-HT does not seem to impose serious health risks. However, more long-term
      study data and direct head-to-head comparisons between various low-dose
      preparations are needed to support or rectify the safety aspects.

PMID- 17034967
TI  - Evaluation of the USP dissolution test method A for enteric-coated articles by
      planar laser-induced fluorescence.
AB  - The USP drug release standard for delayed-release articles method A was evaluated
      using planar laser-induced fluorescence (PLIF). Prior authors have suggested that
      high pH "hot spots" could develop during the buffer medium addition of the method
      A enteric test. Additionally, previous studies have shown heterogeneous flow
      patterns and low-shear regions in the USP Apparatus II dissolution vessel, which
      may result in poor mixing of the buffer and acid media during the pH
      neutralization step of the method A enteric test. In this study, PLIF was used to
      evaluate the mixing patterns and evolution of pH neutralization during the buffer
      medium addition with rhodamine-B dye and the pH-sensitive dye fluorescein,
      respectively. Additionally, a comparison of the methods A and B enteric tests was
      performed with enteric-coated tablets containing rhodamine-B in the film so as to
      image the dissolution rate of the coating polymer with PLIF in order to determine
      if rapid buffer addition for the method A procedure accelerates the rate of film
      coat dissolution. Rapid addition of the 250 mL of buffer medium over 5 s to the
      750 mL of acidic medium shows efficient mixing and pH neutralization due to the
      generation of large-scale stirring and enhanced turbulence resulting from the
      descending buffer medium. Slow addition near the paddle shaft over 5 min showed
      segregation in the recirculating region around the paddle shaft. In contrast,
      slow addition near the vessel wall introduces the medium into fluid outside of
      the recirculation region and enables transport over the entire vessel. Enteric
      coated tablets tested according to method A with rapid medium addition and method
      B enteric tests performed identically, indicating no difference in polymer
      dissolution rate between the two tests. From the results of the PLIF imaging
      studies with rhodamine-B, fluorescein, and enteric-coated tablets, it was seen
      that "hot spots" affecting the dissolution performance of enteric dosage forms
      are not generated during the neutralization step of the method A enteric test
      namely when the media is added rapidly or outside of the recirculating region
      that surrounds the paddle shaft.

PMID- 17034968
TI  - Bioavailability of riboflavin from a gastric retention formulation.
AB  - A gastric retention formulation (GRF) made of naturally occurring carbohydrate
      polymers and containing riboflavin was tested in vitro for swelling and
      dissolution characteristics as well as in fasting dogs for gastric retention. The
      bioavailability of riboflavin, a drug with a limited absorption site in the upper
      small intestine, from the GRF was studied in fasted healthy humans and compared
      to an immediate release formulation. It was found that when the GRF is dried and
      immersed in gastric juice it swells rapidly and releases its drug content in a
      zero-order fashion for a period of 24 h. In vivo studies in dogs showed that a
      rectangular shaped GRF stayed in the stomach of fasted dogs for more than 9 h,
      then disintegrated and reached the colon in 24 h. Endoscopic studies in dogs
      showed that the GRF hydrates and swells back to about 75% of its original size in
      30 min. These in vivo results correlated with in vitro results. Pharmacokinetic
      parameters determined from urinary excretion data from six human subjects under
      fasting conditions showed that bioavailability depended on the size of the GRF.
      The biostudy indicated that bioavailability of riboflavin from a large size GRF
      was more than triple that measured after administration of an immediate release
      formulation. Deconvolved input functions from biostudy data suggest that the
      large size GRF stayed in the stomach for about 15 h.

PMID- 17034970
TI  - Wound healing activity of embelin isolated from the ethanol extract of leaves of
      Embelia ribes Burm.
AB  - Ethanol extract of the leaves of Embelia ribes Burm. (Myrsinaceae) and its
      isolated quinone compound embelin were screened for wound healing activity by
      excision, incision and dead space wound models on Swiss Albino Rats. Significant
      wound healing activity was observed in both ethanol crude extract (30 mg/ml) and
      the constituent treated groups. In embelin treated groups (4 mg/ml of 0.2% sodium
      alginate gel), epithelialization of the incision wound was faster with a high
      rate of wound contraction. The tensile strength of the incision wound was
      significantly increased than the ethanol extract. In dead space wound model also
      the weight of the granulation was increased indicating increase in collagenation.
      The histological examination of the granulation tissue of embelin treated group
      showed increased cross-linking of collagen fibers and absence of monocytes. The
      wound healing effect was comparatively evaluated with the standard skin ointment
      Framycetin.

PMID- 17034969
TI  - Antimicrobial and anti-inflammatory activity of four known and one new
      triterpenoid from Combretum imberbe (Combretaceae).
AB  - Combretum imberbe is used widely in Africa inter alia for treating bacterial
      infections. In addition to four known triterpenoids, 1alpha,3beta-dihydroxy-12
      oleanen-29-oic (1), 1-hydroxy-12-olean-30-oic acid (2), 3,30-dihydroxyl-12
      oleanen-22-one (3), and 1,3,24-trihydroxyl-12-olean-29-oic acid (4), a new
      pentacyclic triterpenoid (1alpha,23-dihydroxy-12-oleanen-29-oic acid-3beta-O-2,4
      di-acetyl-L-rhamnopyranoside) 5 has been isolated through a bioassay-guided
      procedure from the leaves of Combretum imberbe. The structures of the compounds
      were elucidated on the basis of 1D and 2D NMR experiments, as well as mass
      spectrometric data. All compounds isolated had moderate (62 microg/ml) to strong
      (16 microg/ml) antibacterial activity (MIC values) against Staphylococcus aureus
      and Escherichia coli, with 1 and 5 being most active. Compounds 1 and 5 also
      showed very strong inhibition of 3alpha-hydroxysteroid dehydrogenase with an
      IC(50) of 0.3 microg/ml. Compound 5 indicated a moderate anti-proliferative
      (GI(50)=16.5 and 13.2 microg/ml) and cytotoxic activity (CC(50)=17.6 micro/ml)
      against K-562, L-929 and HeLa cell lines, respectively. The results of this study
      give credence to the ethnomedicinal use of Combretum imberbe and expand our
      knowledge on the biological activity of its metabolites.

PMID- 17034971
TI  - Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration
      and lipid profile in normal and streptozotocin-induced diabetic rats.
AB  - The objective of this study was to investigate the effects of Orthosiphon
      stamineus Benth. aqueous extract on plasma glucose concentration and lipid
      profile in normal and streptozotocin-induced diabetic rats. The chemical
      screening of the extract showed phenolic compound and flavonoid content were
      13.24+/-0.33 mg/g and 1.73+/-0.14 microg/g, respectively. In oral glucose
      tolerance test, the extract (0.2-1.0 g/kg) significantly decreased plasma glucose
      concentration in a dose-dependent manner in both normal and diabetic rats. The
      extract at 1.0 g/kg was most effective in decreasing plasma glucose
      concentrations and the response was closed to the result of glibenclamide (5
      mg/kg). After repeated daily oral administrations of the extract (0.5 g/kg) for
      14 days, the extract significantly reduced plasma glucose concentration in
      diabetic rats at days 7 and 14. By the end of the study, plasma triglyceride
      concentration was lower in the extract-treated diabetic rats than untreated ones.
      Furthermore, plasma HDL-cholesterol concentration was significantly increased in
      diabetic rats treated with the extract. In perfused rat pancreas, the extract did
      not increase insulin secretion in the presence of 5.5 mM glucose, but 100
      microg/ml extract potentiated glucose-induced insulin secretion. Our findings
      suggested that Orthosiphon stamineus aqueous extract is effective for alleviating
      hyperglycemia and improving lipid profile in diabetic rats.

PMID- 17034973
TI  - Identification of novel genes expressed in hypoxic brain condition by
      fluorescence differential display.
AB  - Fluorescence differential display (FDD) and comparative RT-PCR have been used
      extensively to detect differentially expressed genes. We investigated hypoxia
      induced gene expression in the brain by FDD-PCR and comparative RT-PCR. Mice were
      anaesthetized after which hypoxia was induced by neck ligation for 1 min or 25
      min, then were killed by decapitation, and the brains were dissected either
      immediately or 30 min after death (Group A1-0, Group A25-0, Group A1-30 and Group
      A25-30). Control mice without ligation of the neck were killed by decapitation
      under anaesthesia immediately (Group C-0) or 30 min after death (Group C-30). FDD
      PCR, sequence analysis and comparative RT-PCR revealed that mitochondrial
      thymidine kinase 2, Rab6, selenoprotein T and two novel cDNAs were enhanced in
      Group A25-0 and Group A25-30 compared with the other groups. In Group A25-30,
      only RAP2 interacting protein and another novel cDNA were induced. In Group A25
      0, one novel gene was detected. These findings were consistent with the results
      of statistical analysis by ANOVA. No differences of band pattern were observed
      among Groups A1-0, A1-30, C-0 and C-30. The genes exhibiting altered expression
      were associated with vital cellular functions, e.g., intracellular signaling and
      mitochondrial metabolism. In addition, we identified four novel genes, expressed
      after extended hypoxic conditions in mouse brain with suffocation. These results
      may contribute to clarify the pathophysiology of asphyxia in the brain and aid in
      the diagnosis of suffocation.

PMID- 17034974
TI  - Transient abducens nerve palsy during endoscopic sinus surgery: report of three
      cases.
AB  - Dysfunction of one or more of the ocular motor nerves or extraocular muscle
      injury commonly results in diplopia. Diplopia during endoscopic sinus surgery is
      caused by surgical trauma or local anesthetics. Transient abducens nerve palsy
      rarely occurs after an intranasal sphenopalatine nerve block. We report three
      cases of transient abducens nerve palsy during endoscopic sinus surgery and
      possible explanations are proposed with a review of literature.

PMID- 17034975
TI  - Initial experience with lung-MRI at 3.0T: Comparison with CT and clinical data in
      the evaluation of interstitial lung disease activity.
AB  - OBJECTIVES: We evaluated the feasibility of highfield lung-MRI at 3.0T. A
      comparison with Computed Tomography (CT) and clinical data regarding the
      assessment of inflammatory activity in patients with diffuse lung disease was
      performed. MATERIAL AND METHODS: Prospective evaluation of 21 patients (15 males,
      6 females, 43-80 y) with diffuse lung diseases who underwent clinical work-up
      inclusive laboratory tests, lung-function tests and transbronchial biopsy. After
      routine helical CT (additional 12 HRCT) a lung-MRI (3.0 Intera, Philips Medical
      Systems, Best, The Netherlands) using a T2-weighted, cardiac and respiratory
      triggered Fast-Spinecho-Sequence (TE/TR=80/1500-2500 ms, 22 transverse slices,
      7/2mm slice-thickness/-gap) was performed. A pneumologist classified the cases
      into two groups: A=temporary acute interstitial disease or chronic interstitial
      lung disease with acute episode or superimposed infection/B=burned out
      interstitial lung disease without activity. Two blinded CT-radiologists graded
      the cases in active/inactive disease on the basis of nine morphological criteria
      each. A third radiologist rated the MRI-cases as active/inactive, depending on
      the signal-intensities of lung tissues. RESULTS: The pneumologist classified 14
      patients into group A and 7 patients into group B. Using CT, 6 cases were
      classified as active, 15 cases as inactive disease. With MRI 12 cases were
      classified as active and 9 cases as inactive. In the complete group of 21
      patients MRI decisions and CT decisions respectively were false positive/false
      negative/correct in 2/4/15 respectively 0/8/13 cases. Correct diagnoses were
      obtained in 72% (MRI) respectively 62% (CT). In the subgroup of 12 cases
      including HRCT, MRI respectively CT were false positive/false negative/correct in
      2/1/9 respectively 0/5/7 cases. Correct diagnoses were obtained in 75% (MRI)
      respectively 58% (CT). CONCLUSION: Highfield MRI of the lung is feasible and
      performed slightly better compared to CT in the determination of activity in
      patients with interstitial lung diseases.

PMID- 17034976
TI  - Determination of ganciclovir in different matrices from solid organ transplanted
      patients treated with a wide range of concomitant drugs.
AB  - The aim of the present study was to develop a time-efficient chromatographic
      method for the analysis of therapeutic concentrations of ganciclovir (GCV) in
      plasma, urine as well as dialysate (from continuous renal replacement therapy)
      from solid organ transplant recipient treated with either GCV or its prodrug
      valganciclovir (VGCV) in combination with a wide variety of other concomitant
      drugs. Sample preparation was performed by reversed phase solid phase extraction
      and was followed by separation of the analytes on a reversed phase column using
      isocratic elution with a mobile phase consisting of acetonitrile-a counter ion
      (50 mM 1-heptanesulfonic acid) in an aqueous sodium dihydrogen phosphate buffer
      (pH 2.1; 10 mM) (10:90 v/v) and a fluorescence detector. Validation of the method
      showed linearity within the concentration range of 0.1-40 microg/mL for plasma
      and 0.1-120 microg/mL for urine and dialysate (R(2)>0.99, n> or =5). Accuracy and
      precision (evaluated at 0.1, 5 and 40 microg/mL) were both satisfactory. The LLOQ
      was determined to be 0.1 microg/mL. The method was successfully applied on
      clinical samples from renal transplant recipients treated with VGCV in
      combination with a variety of usually used concomitant drugs for solid organ
      transplant recipients.

PMID- 17034977
TI  - Rapid and simultaneous determination of sulfamethoxazole and trimethoprim in
      human plasma by high-performance liquid chromatography.
AB  - A simple and reproducible high-performance liquid chromatographic method was
      developed for simultaneous determination of sulfamethoxazole (SMX) and
      trimethoprim (TMP) in human plasma. The method entailed injection of the samples
      after deproteination with perchloric acid and subsequent neutralizing. Primidone
      was used as internal standard. Chromatography was performed on a C(18) column
      (250 mm x 4.6 mm, 5 microm) under isocratic elution with 50 mM aqueous sodium
      dihydrogen phosphate-acetonitrile-triethylamine (100:25:0.5, v/v), pH 5.9.
      Detection was made at 240 nm and analyses were run at a flow-rate of 1.5 ml/min
      at a temperature of 35 degrees C. The recovery was 83.4, 88.5 and 98.2% for TMP,
      SMX and internal standard, respectively. The precision of the method was 2.6-9.8%
      over the concentration range of 0.125-2 microg/ml for TMP and 0.39-50 microg/ml
      for SMX. The limit of quantification (LOQ) in plasma was 0.125 and 0.39 microg/ml
      for TMP and SMX, respectively. The method was used for a bioequivalence study.

PMID- 17034978
TI  - Evaluation of an International Pharmacopoeia method for the analysis of
      saquinavir (mesilate) bulk drugs by liquid chromatography.
AB  - A single gradient LC method for the determination of related substances in both
      saquinavir (SQV), saquinavir mesilate (SQVM) has been published in a consultation
      document of the International Pharmacopoeia, WHO Drug Information. The method
      uses a base deactivated reversed phase C18 column (25 cm x 4.6 mm i.d.), 5 microm
      kept at a temperature of 30 degrees C. The mobile phases consist of acetonitrile,
      methanol, phosphate buffer pH 3.4 and water. The flow rate is 1.0 ml/min. UV
      detection is performed at 220 nm. A system suitability test (SST) is described to
      govern the quality of the separation. The separation towards SQV(M) components
      was investigated on 18 C18 columns and correlation was made with the column
      classification system developed in our laboratory. The method was evaluated using
      a Hypersil BDS C18 column (25 cm x 4.6 mm i.d.), 5 microm. A central composite
      design was applied to examine the robustness of the method. The method shows good
      precision, linearity, sensitivity and robustness. SQV(M) commercial samples of
      bulk drugs were examined using this method.

PMID- 17034979
TI  - Quantification of olanzapine polymorphs using powder X-ray diffraction technique.
AB  - Accurate quantification of crystalline phases present in drug materials is
      becoming increasingly important, due to stringent regulatory concerns about
      polymorph characterization and control in drug substances and products. In the
      present study, a quantification method for polymorphic forms of olanzapine (OLZ)
      has been developed using powder X-ray diffraction (PXRD). Preferred orientation
      has been reported to be the major source of error in PXRD analysis, therefore,
      prior to development of a quantification method, pure polymorphic forms (I and
      II) of different size ranges were analyzed. Preferred orientation effect was
      found to decrease on using sieve fraction BSS # 120/240 for form I. In order to
      obtain good peak resolution in optimum time, the step time and step size were
      varied so as to optimize the scan rate. Among the five combinations selected,
      step size of 0.05 degrees with step time of 5s demonstrated identification of
      four characteristic peaks of form I in form II in 62 min. A calibration curve was
      constructed in the range of 0-100% (w/w) using the characteristic peak of form I
      at 18.48 degrees 2theta (I/I(0) 78.8%). The PXRD assay was reproducible and
      precise and displayed a LOD of 0.40% (w/w) and LOQ of 1.22% (w/w). Validation
      results showed excellent correlation between actual and predicted concentrations
      with R(2) 0.9999.

PMID- 17034980
TI  - Determination of kava lactones and flavonoid glycoside in Scorzonera austriaca by
      capillary zone electrophoresis.
AB  - A capillary zone electrophoretic method has been developed for the quantitative
      analysis of three active comppounds, 12-hydroxy-desmethoxyyangonin (HD), 12-beta
      d-glucopyranoside-desmethoxyyangonin (GD) and luteolin 3'-(6-E-p-coumaroyl-beta-d
      glucopyranoside) (LG) in Scorzonera austriaca with UV detection at 254 nm. The
      applied voltage was 25 kV and the capillary temperature was kept constant at 25
      degrees C. The effect of buffer pH, the concentration of electrolyte and organic
      modifier on migration were studied systematically. Optimum separation was
      achieved with 20 mM borate buffer at pH 10.00 containing 10% (v/v) methanol.
      Daphnetin was used as internal standard for quantification. Regression equations
      revealed good linear relationship between the ratios of the peak area of each
      compound and its the ratios of concentration. All the correlation coefficients
      were higher than 0.9990. The relative standard deviations of migration time and
      the peak area were <1.46% and 5.13% (inter-day), and <1.65% and 5.16% (intra
      day), respectively. The contents of the three compounds in S. austriaca were
      successfully determined with satisfactory repeatability and recovery.

PMID- 17034981
TI  - Packed-bed bioreactors for mammalian cell culture: bioprocess and biomedical
      applications.
AB  - This article describes the development history of packed-bed bioreactors (PBRs)
      used for the culture of mammalian cells. It further reviews the current
      applications of PBRs and discusses the steps forward in the development of these
      systems for bioprocess and biomedical applications. The latest generation of PBRs
      used in bioprocess applications achieve very high cell densities (>10(8) cells
      ml(-1)) leading to outstandingly high volumetric productivity. However, a major
      bottleneck of such PBRs is their relatively small volume. The current maximal
      volume appears to be in the range of 10 to 30 l. A scale-up of more than 10-fold
      would be necessary for these PBRs to be used in production processes. In
      biomedical applications, PBRs have proved themselves as compact bioartificial
      organs, but their metabolic activity declines frequently within 1 to 2 weeks of
      operation. A main challenge in this field is to develop cell lines that grow
      consistently to high cell density in vitro and maintain a stable phenotype for a
      minimum of 1 to 2 months. Achieving this will greatly enhance the usefulness of
      PBR technology in clinical practice.

PMID- 17034982
TI  - Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells
      in the supraoptic hypothalamus is reduced in calorically restricted mice.
AB  - Both life-long caloric restriction (CR) and the suppression of insulin-like
      growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The
      neuroendocrine system, regulated by the hypothalamus, remains the most convincing
      site of action for both these modes of life extension. Yet, determining whether
      CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling
      remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF
      1R), the cells of the supraoptic nucleus (SON) display some of the most robust
      IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to
      IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON
      of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22
      months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An
      automated imaging microscopy system (AIMS) was used to generate cell counts for
      each section of supraoptic hypothalamus. Results show that while the total number
      of cells in the SON of ad-libitum fed mice does not change significantly with
      aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad
      libitum fed mice with aging. In contrast to this, calorie restricted mice show
      both a decline in the total number of cells and IGF-1R immunoreactive cells in
      the SON with age, but with the decrease in the latter being notably attenuated
      when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR
      induces greater loss in the total number of cells in the SON with age, it reduces
      the degree of age-dependent loss seen in IGF-1R expressing cells. As a result,
      when compared to Old-AL mice, the SON of Old-CR mice displays a greater
      proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with
      aging.

PMID- 17034983
TI  - Differential activities in adhesion and neurite growth of fibronectin type III
      repeats in the PTP-delta extracellular domain.
AB  - The full-length extracellular domain (ECD) of protein tyrosine phosphatase delta
      (PTP-delta) functions as a ligand to promote cell adhesion and neurite outgrowth;
      this ECD contains three immunoglobulin (Ig) repeats and eight fibronectin type
      III (FN III) repeats. However, it is not known which regions of the ECD regulate
      its ligand functions. Therefore, we constructed and expressed a fusion protein of
      the PTP-delta ECD lacking FN III repeats 4-8, and tested this protein for
      neuronal adhesion and neurite-promoting ability. Compared to the full-length
      isoform, the truncated ECD was poorer at promoting adhesion, but a more potent
      promoter of neurite growth. The results suggest that distal FN III repeats of PTP
      delta are important in adhesive functions, but dispensable for neurite outgrowth
      promotion. As the predominant isoform of PTP-delta during neural development
      (type D) also lacks distal FN III repeats, the functional properties we observe
      may be relevant to periods of axon extension, suggesting that splice variants of
      receptor PTPs play distinct roles in neural development.

PMID- 17034984
TI  - Intrastriatal hypoxanthine administration affects Na+,K+-ATPase,
      acetylcholinesterase and catalase activities in striatum, hippocampus and
      cerebral cortex of rats.
AB  - The aim of this study was to investigate the effects of a single intrastriatal
      injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan
      disease, on Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities in
      striatum, cerebral cortex and hippocampus of rats at different post-infusion
      periods. Adult Wistar rats were divided in two groups: (1) vehicle-injected group
      (control) and (2) hypoxanthine-injected group. For Na(+),K(+)-ATPase activity
      determination, the animals were sacrificed 3h, 24h and 7 days after drug
      infusion. For the evaluation of acetylcholinesterase and catalase activities, the
      animals were sacrificed 30min, 3h, 24h and 7 days after hypoxanthine infusion.
      Results show regional and time dependent effects of hypoxanthine on Na(+),K(+)
      ATPase, acetylcholinesterase and catalase activities. The in vitro effect of
      hypoxanthine on the same enzymes in striatum was also investigated. Results
      showed that hypoxanthine inhibited Na(+),K(+)-ATPase, but not the activities of
      acetylcholinesterase and catalase in rat striatum. We suggest that these
      modification on cerebral biochemical parameters (Na(+),K(+)-ATPase,
      acetylcholinesterase and catalase activities) induced by intrastriatal
      administration of hypoxanthine in all cerebral structures studied, striatum,
      hippocampus and cerebral cortex, could be involved in the pathophysiology of
      Lesch-Nyhan disease.

PMID- 17034985
TI  - Estrogen and androgen receptor expression in relation to steroid concentrations
      in the adult boar epididymis.
AB  - The steroid hormone regulation of the epididymis in a high estrogen producing
      animal like the boar is not currently understood. To test the hypothesis that the
      boar epididymis is an estrogen and androgen responsive tissue, the presence of
      estrogen and androgen receptors, in conjunction with steroid hormone
      concentrations were investigated in the boar epididymis. Epididymal (caput,
      corpus, cauda) and testicular samples of boars (1-2.5 years; n=5) were collected
      for immunolocalization of estrogen receptor alpha (ERalpha), estrogen receptor
      beta (ERbeta) and androgen receptor (AR). Concentrations of testosterone,
      estradiol and estrogen conjugates (EC) in the tissue were also determined. AR and
      ERbeta were localized in the principal and basal cells of all three epididymal
      regions. ERalpha was localized in the principal cells of the caput, some cells of
      the corpus and was not present in the cauda. Testosterone (p<0.0001), estradiol
      (p<0.0001) and EC (p<0.005) were significantly lower in the epididymis compared
      with the testis. The epididymal regions were not significantly different from
      each other for testosterone (p>0.15) or estradiol (p>0.09). EC were significantly
      higher in the corpus than either the caput (p=0.003) or cauda (p=0.002). These
      results suggest that the boar epididymis is responsive to both estrogens and
      androgens and that both steroid hormones are important for proper epididymal
      function. Since testosterone and estradiol concentrations are similar throughout
      the epididymis, regional differences in steroid hormone regulation are likely due
      to differences in receptor expression.

PMID- 17034986
TI  - [Heparin-induced thrombocytopenia: report of four cases in severely burned
      patients].
AB  - Heparin-induced thrombocytopenia (HIT) is a dangerous complication of heparin
      therapy caused by an antibody against heparin/Platelet Factor 4 (PF4) complex.
      HIT complicates about 2% of treatment with unfractionated heparin (UFH). The aim
      of the study was to determine the incidence of HIT in a burn center and to report
      four cases in severely burned patients. HIT was documented in 2.8% of burns
      treated with UFH administered for antithrombotic prophylaxis and in none of burns
      receiving low molecular weight heparin (LMWH). All HIT cases occurred after
      extensive deep burns (mean total body surface area or TBSA was 60+/-21%) and
      three cases had above 75% of burn. We suggest that systemic platelet activation
      after thermal injury and local production of PF4 in the burn wound could
      participate to development of HIT. The risk is a late diagnosis since thrombosis
      clinical detection under burned skin is difficult. HIT appears during the first
      week of UHF treatment at the same time as a unstable period of fluctuating
      platelets.

PMID- 17034987
TI  - Maternal diabetes in vivo and high glucose concentration in vitro increases
      apoptosis in rat embryos.
AB  - Apoptosis may be involved in diabetes-induced embryonic dysmorphogenesis. We
      estimated the occurrence of apoptosis in embryos of a rat model for diabetic
      pregnancy. We found decreased Bcl-2, increased Bax and cleaved Caspase 3 proteins
      in embryos from diabetic rats. Moreover, we found increased activation of Caspase
      3 in cells from embryos previously exposed to a diabetes-like environment (in
      vivo, in vitro) compared to cells from control embryos, which was normalized by
      supplementation of N-acetylcysteine or apoptosis inhibitor. We detected increased
      propidium iodide uptake in embryonic cells exposed to maternal diabetes, a
      finding confirmed by vital staining. Additionally, we found increased
      dysmorphogenesis in embryos exposed to a diabetic environment in vivo and in
      vitro. Exposure to a diabetic milieu during organogenesis increases apoptosis in
      embryonic cells and dysmorphogenesis in embryos. Enhanced apoptotic rate may have
      a role in diabetic embryopathy by inducing disturbed embryonic maturation,
      increased rates of resorptions and congenital malformations.

PMID- 17034988
TI  - Glycine reduces cadmium-induced teratogenic damage in mice.
AB  - The effect of glycine in preventing cadmium (Cd) teratogenicity in mice was
      studied. Cadmium chloride (CdCl2) was administered subcutaneously at 1, 2 or 4
      mg/kg doses on gestation days (GD) 7, 8 and 9. Glycine was given ad libitum (in
      the drinking water) from GD0 through GD18 (the day when animals were killed), as
      a 1% and 2% drinking water solution. Cd and nucleic acid concentrations in
      embryos were determined. The most common finding seen after CdCl2 4 mg/kg
      exposure was exencephaly. The incidence of this malformation was significantly
      reduced in mice receiving 2% glycine while fetal Cd significantly decreased as
      compared to cadmium-treated positive control animals. Increased nucleic acid
      levels were seen in the same embryos. In glycine non-supplemented mice given
      CdCl2 4 mg/kg, embryonic lipid peroxidation proved to be increased. In
      conclusion, lipid peroxidation was associated with cadmium-induced
      teratogenicity, and glycine inhibited the cadmium-induced effect by inhibiting
      placental transport of cadmium. However, further detailed studies are needed to
      establish the mechanism(s) of action.

PMID- 17034989
TI  - Nonverbal social interaction skills of children with learning disabilities.
AB  - Many children with learning disabilities (LD) face problems in their nonverbal
      communication, which constitutes an important component of their social skills.
      This study explores the frequency of nonverbal initiations and responses of 36
      children with LD and 36 children without LD matched for age and gender, who were
      observed for 40 min during the break. Younger and older children with and without
      LD did not differ significantly in their nonverbal responses, but there was a
      statistically significant difference in terms of younger children's nonverbal
      initiations. Younger children with LD exhibited significantly fewer nonverbal
      initiations than younger children without LD. Findings are discussed and
      suggestions are made for further research.

PMID- 17034990
TI  - Brief review of current research in FXS: implications for treatment with
      psychotropic medication.
AB  - The purpose of this paper is to provide a brief review of current research in
      fragile X syndrome (FXS) with regards to the morphology and behavioral phenotype
      associated with FXS and the use of psychotropic medication for the treatment of
      behavior problems (e.g., aggression) often seen in FXS (full mutation). The lack
      of production of the fragile X mental retardation protein (FMRP) is associated
      with FXS and has been found to result in various neuronal changes such as altered
      dendritic morphology and function as well as altered neurotransmitter functions.
      A review of the basic literature on animal models and the relevance of these
      findings for the use of psychotropic treatment of problem behaviors in FXS will
      be discussed. Future research directions will be presented.

PMID- 17034991
TI  - Robust rigid registration of retinal angiograms through optimization.
AB  - Retinal fundus photographs are employed as standard diagnostic tools in
      ophthalmology. Serial photographs of the flow of fluorescein and indocyanine
      green (ICG) dye are used to determine the areas of the retinal lesions. For
      objective measurements of features, the registration of the images is a
      necessity. In this paper, we employ optimization techniques for registration with
      the help of 2-parameter translational motion model of retinal angiograms, based
      on non-linear pre-processing (Wiener filtering and morphological gradient) and
      computation of the similarity criteria for the alignment of the two gradient
      images for any given rigid transformation. The optimization methods are
      effectively employed to minimize the similarity criterion. The presence of noise,
      the variations in the background and the temporal variation of the fluorescence
      level pose serious problems in obtaining a robust registration of the retinal
      images. Moreover, local search strategies are not robust in the case of ICG
      angiograms, even if one uses a multiresolution approach. The present work makes a
      systematic comparison of different optimization techniques, namely the
      minimization method derived from the optical flow formulation, the Nelder-Mead
      local search and the HCIAC ant colony metaheuristic, each optimizing a similarity
      criterion for the gradient images. The impact of the resolution and median
      filtering of gradient image is studied and the robustness of the approaches is
      tested through experimental studies, performed on macular fluorescein and ICG
      angiographies. Our proposed optimization techniques have shown interesting
      results especially for high resolution difficult registration problems. Moreover,
      this approach seems promising for affine (6-parameter motion model) or elastical
      registrations.

PMID- 17034992
TI  - Penetration of moxifloxacin into sternal bone of patients undergoing routine
      cardiopulmonary bypass surgery.
AB  - This study investigated plasma and bone concentrations of moxifloxacin following
      a single intravenous dose of 400mg to consider its potential role in the
      treatment of osteomyelitis. Eight patients who underwent routine cardiopulmonary
      bypass surgery were enrolled in the study. Plasma and bone samples were collected
      2h and 5h after the end of infusion. High performance liquid chromatography was
      used for the determination of moxifloxacin concentrations. Mean plasma
      concentrations were 3.36 microg/mL and 2.93 microg/mL at 2h and 5h after the end
      of infusion. The concentrations in the body and manubrium of the sternal bone
      were 1.65 microg/g and 1.64 microg/g at 2h and 1.4 microg/g and 1.45 microg/g at
      5h, respectively. Moxifloxacin showed good penetration into bone and could be
      considered for the treatment of osteomyelitis.

PMID- 17034993
TI  - Multi-azole resistance in Aspergillus fumigatus.
AB  - Azole resistance in Aspergillus spp. is unusual. We report a patient who received
      long-term treatment with itraconazole and voriconazole for bilateral chronic
      cavitary aspergillosis with aspergillomas whose isolates of Aspergillus fumigatus
      developed simultaneous resistance to itraconazole and voriconazole. A novel
      mutation (G138C) in the target gene (cyp51A) encoding 14alpha-demethylase was
      detected. The patient had some response to intravenous caspofungin, which he
      received six times weekly, without the development of resistance over 9 months.

PMID- 17034994
TI  - Stem cell based therapies to treat muscular dystrophy.
AB  - Muscular dystrophies comprise a heterogeneous group of neuromuscular disorders,
      characterized by progressive muscle wasting, for which no satisfactory treatment
      exists. Multiple stem cell populations, both of adult or embryonic origin,
      display myogenic potential and have been assayed for their ability to correct the
      dystrophic phenotype. To date, many of these described methods have failed,
      underlying the need to identify the mechanisms controlling myogenic potential,
      homing of donor populations to the musculature, and avoidance of the immune
      response. Recent results focus on the fresh isolation of satellite cells and the
      use of multiple growth factors to promote mesangioblast migration, both of which
      promote muscle regeneration. Throughout this chapter, various stem cell based
      therapies will be introduced and evaluated based on their potential to treat
      muscular dystrophy in an effective and efficient manner.

PMID- 17034995
TI  - Xenopus cadherin-6 regulates growth and epithelial development of the retina.
AB  - Cadherins are crucial for tissue cohesion, separation of cell layers and cell
      migration during embryogenesis. To investigate the role of classical type II
      Xcadherin-6 (Xcad-6), we performed loss-of-function studies by morpholino
      oligonucleotide injections. This resulted in severe eye defects which could be
      rescued with murine cadherin-6. In the absence of Xcadherin-6, morphological
      alterations and a decrease in cell proliferation were observed with eye cup
      formation. Eye field transplantations of Xcadherin-6 depleted donors yielded
      grafts that failed to form a proper neuroepithelium in a wildtype environment. At
      later developmental stages Xcadherin-6 deficient eyes showed lamination defects
      in the outer neural retina, a reduced thickness of the ganglion cell layer (GCL)
      and a fragmented retina pigment epithelium (RPE). Thus, Xcadherin-6 is essential
      early in eye development for structural organization and growth of the
      neuroepithelium before it differentiates into neural retina and RPE.

PMID- 17034996
TI  - Conformational analysis of protein secondary structure during spray-drying of
      antibody/mannitol formulations.
AB  - Inhalation of spray-dried particles is a promising delivery route for proteins as
      an alternative to injection. Changes in the protein structure and aggregation
      have to be avoided. The effect of mannitol, a stabilizing agent typically used in
      both liquid and lyophilized protein formulations, on an antibody (IgG1) in a
      spray-dried powder was studied using different biophysical and chromatographic
      techniques. At first, different solutions composed of antibody (IgG1) and
      mannitol at a ratio between 20/80 and 100/0 IgG1/mannitol (100 mg/ml total solid)
      were investigated for their stability. Protein solutions containing the IgG1
      showed mannitol-dependent aggregation. High amounts of mannitol (50-80%) exerted
      a destabilizing effect on the antibody and the aggregate 9 level increased to 2.6
      4.2%. In contrast, solutions with only 20-40% mannitol showed the same amount of
      aggregates as the pure antibody solution. The antibody mannitol solutions were
      investigated by circular dichroism (CD) and Fourier transform infrared
      spectroscopy (FTIR) to evaluate whether changes in the protein secondary
      structure can be correlated with aggregation. Considering the sensitivity of the
      used methods and data evaluation, FTIR spectra did not reveal structural changes
      in the IgG1/mannitol solutions compared to the pure antibody, despite varying
      aggregate levels. Thermal stress was reflected in perturbations of the secondary
      structure, but mannitol-dependent aggregation could not be correlated to
      detectable alterations in the FTIR spectra. Analyzing the CD spectra revealed no
      distinctive change in the shape of the CD curve, indicating that the protein
      secondary structure is mainly retained. This is in agreement with the infrared
      data. Subsequently, the IgG1/mannitol solutions were spray-dried at Tin/Tout of
      90/50 degrees C. Using ATR-FTIR for the investigation of the protein amide I band
      in the spray-dried powder revealed changes in the sub-components of the amide I
      band. This indicates that the peptide groups (CO and NH) of the protein are found
      in a different environment in the solid state, compared to the liquid protein
      formulation. After redissolution of the powders, the native structure of the pure
      antibody solution was found identical to the protein secondary structure before
      spray-drying, indicating that the protein secondary structure is not strongly
      altered in the dry state, and not affected by the spray-drying process. Thus,
      from the presented study it can be concluded that the formation of antibody
      aggregates in mannitol formulations cannot be correlated with significant
      perturbations of the protein secondary structure elements.

PMID- 17034997
TI  - Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by
      reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic
      cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic
      cancer.
AB  - BACKGROUND: Matrix metalloproteinases (MMP) are proteolytic enzymes which degrade
      the extracellular matrix and therefore play an important role in metastasis.
      However, the impact of MMP inhibitors (MMPI) on pancreatic cancer is still
      unclear. Thus we evaluated the influence of selective MMPI Ro 28-2653 on the
      incidence of liver metastases and the concentration of MMP-2 and MMP-9 in ductal
      pancreatic adenocarcinoma in Syrian hamster. MATERIAL AND METHODS: One hundred
      and thirty male Syrian hamsters were randomised into 8 groups (Gr.1-3: n=15, Gr.4
      8: n=17). Pancreatic cancer was induced by weekly subcutaneous injection of 10mg
      N-nitrosobis-2-oxopropylamin (BOP)/kg body weight (Gr.4-8) while healthy control
      Gr. 1-3 received 0.5 ml sodium chloride 0.9%. Gr.1 and 4 had free access to a
      standard diet, Gr. 2, 3 and 5-8 received a diet rich in polyunsaturated fatty
      acids, which increases liver metastasis in this model. In week 17 oral therapy
      started: Gr.3 and 6: 60 mg Eudragit/kg body weight/d (vehicle of MMPI), Gr.7 and
      8: 40 mg, respectively, 120 mg RO 28-2653/kg body weight/d; Gr.1, 2, 4, 5: no
      therapy. After 30 weeks all hamsters were sacrificed and histopathologically
      examined. Additionally concentrations of MMP-2 and MMP-9 were measured in non
      metastatic liver and liver metastases. RESULTS: Concentrations of MMP-2 and MMP-9
      in liver metastases were decreased by high- and low-dose therapy with MMPI.
      Furthermore, the incidence of liver metastases was significantly reduced by low
      dose therapy with Ro 28-2653. CONCLUSION: Low-dose therapy with Ro 28-2653
      decreased liver metastasis due to an inhibition of MMP-2 and MMP-9 concentration
      in ductal pancreatic cancer.

PMID- 17034998
TI  - Eosinophil cationic protein: is it useful in asthma? A systematic review.
AB  - INTRODUCTION: Eosinophil cationic protein (ECP) has been widely investigated as a
      potential biomarker of airway inflammation. METHOD: A systematic review was
      performed using Medline with key terms eosinophil cationic protein and asthma,
      limiting the search to titles or abstracts. Out of 688 potential papers found,
      abstracts were reviewed based on the following criteria: (1) ECP was used as a
      biological marker, (2) asthma was the index disease studied, (3) it was a
      controlled clinical study and (4) ECP was assessed as a diagnostic, assessment or
      management tool. One hundred and sixty-nine articles satisfied the selection
      criteria and their full-text versions were reviewed. Only 53 papers were found to
      provide clinically useful information. RESULTS: ECP has been measured in serum,
      plasma, sputum, saliva and broncho-alveolar lavage fluids but serum and sputum
      are the most established. Levels of ECP in normal and asthmatic subjects in
      various body fluids were identified. ECP correlates well with airway inflammation
      but not airway hyper-responsiveness. It is raised in other atopic diseases and
      hence is not diagnostic for asthma. However, it has been shown to be useful in
      assessing asthma severity, compliance with anti-inflammatory asthma therapy and
      as a guide to tailing down inhaled corticosteroid therapy. Although there is some
      evidence that ECP levels are affected by age, smoking, circadian rhythm and
      seasonal variation, only smoking appears to be of clinical significance.
      DISCUSSION: Despite its limitations, ECP remains potentially useful in asthma
      management. Future research on ECP should focus on using serial measurements and
      combining it with other markers of asthma which may increase its clinical
      usefulness.

PMID- 17034999
TI  - Transcription factors and hormones: new insights into plant cell differentiation.
AB  - Plant development is a continuous process, mainly due to the presence of stem
      cell niches within the root and shoot. The interplay between a host of
      transcription factors determines whether the cells within the meristem maintain
      their stem cell state, differentiate into leaves or form secondary meristems,
      which develop into shoots and flowers. Several recent studies provide new insight
      into how transcription factors and phytohormones interact within meristems to
      control cell proliferation and differentiation.

PMID- 17035000
TI  - A novel dry method for surface modification of SU-8 for immobilization of
      biomolecules in Bio-MEMS.
AB  - SU-8 has been primarily used for structural elements and microfludics components
      in MEMS. Microsystems for biological applications require immobilization of
      biomolecules on the MEMS structures. In order to functionalize SU-8 for such
      purposes, the surface needs to be modified. In this paper, we report a novel dry
      method of surface modification of SU-8 which is compatible with standard
      microfabrication techniques. The surface obtained by spin coating SU-8 (2002) on
      silicon wafer was modified by grafting amine groups using pyrolytic dissociation
      of ammonia in a hotwire CVD setup. To demonstrate the presence of amine groups on
      modified SU-8 surface, the surface characteristic after modification was assessed
      using Fourier transform infrared spectroscopy. The change in SU-8 surface
      morphology before and after surface modification was investigated using atomic
      force microscopy. To show the utility of this process for application in Bio
      MEMS, SU-8 microcantilevers were fabricated and subjected to the same surface
      modification protocol. Following this, the cantilevers were incubated first in a
      suspension of human immunoglobulin (HIgG) and then in FITC tagged goat anti-human
      IgG in order to demonstrate the utility of the surface modification performed.
      The efficacy of the process was assessed by observing the cantilevers under a
      fluorescence microscope.

PMID- 17035001
TI  - Transforming-growth factor beta1 Leu10Pro polymorphism and breast cancer
      morbidity.
AB  - TGF-beta1 has a dual role in carcinogenesis. In this gene, a leucine to proline
      substitution in codon 10 leads to higher circulating levels of TGF-beta1. This
      variant has been studied in relationship to the risk for breast cancer yielding
      contradicting results. We aim to unravel the relationship of this polymorphism
      and the risk of breast cancer. Women participating in the Rotterdam Study
      including 143 patients with incident breast cancer were genotyped for this
      polymorphism. We carried out a logistic regression and a survival analysis using
      age as the time variable. The logistic regression analysis showed an increased
      risk of breast cancer for Proline carriers (OR=1.4; 95% confidence interval
      (CI)=1.1-2.0) versus non-carriers. The survival analysis showed that carriers of
      the same allele had an increased risk of breast cancer (HR=1.4, 95% CI=1.1-2.0)
      against non-carriers. Our data suggest that the TGF-beta1 Leu10Pro polymorphism
      might play a role in breast cancer risk.

PMID- 17035002
TI  - Retroperitoneal lymph node resection in patients with cervical cancer.
AB  - OBJECTIVE: To determine predictive factors precluding complete resection of
      metastatic lymph nodes identified by pre-operative imaging in patients with
      cervical cancer. METHODS: Retrospective clinical review of patients with cervical
      cancer with suspected metastases to pelvic and/or periaortic lymph nodes who
      underwent lymph node dissection by laparotomy at The University of Texas M.D.
      Anderson Cancer Center from September 1990-December 2004. RESULTS: A total of 104
      patients were the subject of this analysis. Post-operatively, 25 patients (24%)
      had negative lymph nodes, 62 patients (60%) had macroscopically positive lymph
      nodes, one patient had microscopically positive (1%) and 16 patients (15%) had
      unresectable lymph nodes. Body mass index did not have any impact on successful
      resection of lymph nodes. On univariate analysis age (p=0.049) and size and
      location of the largest lymph node were associated with resection status (p=0.001
      and 0.020). Logistic regression confirmed that chance of achieving a successful
      resection decreases with increasing age (p=0.046) and size of largest lymph node
      (0.002). CONCLUSIONS: The ability to completely resect suspected metastatic lymph
      nodes at the time of extraperitoneal lymph node dissection in patients with
      cervical cancer is associated with size and location of largest lymph node.

PMID- 17035003
TI  - Decolorization and partial degradation of monoazo dyes in sequential fixed-film
      anaerobic batch reactor (SFABR).
AB  - Decolorization of two monoazo dyes, acid orange 6 (AO6) and acid orange 7 (AO7),
      were studied in sequential fixed-film anaerobic batch reactor (SFABR) with
      varying dye concentrations and 500 mg/L glucose as the co-substrate. More than
      90% dye decolorization could be achieved, even at 300 mg/L, with both AO6 and AO7
      and dye decolorization rates were 168 mg/L/d and 176 mg/L/d, respectively. COD
      removals with these two monoazo dyes were significantly different, as 75% and 35%
      decrease were observed with AO6 and AO7, respectively. UV-visible spectral as
      well as HPLC analysis of SFABR treated effluent showed the accumulation of 4
      aminobenzenesulfonate (4-ABS) from AO6 and AO7. Aminoresorcinol (AR) formed from
      AO6 decolorization could not be detected at the end of SFABR cycle. This along
      with high COD removal indicated its further degradation. Formation of pink
      coloration on exposure to air indicated the presence of 1-amino-2-naphthol (AN)
      in AO7 fed reactor effluent. Thus both 4-ABS and AN were resistant to further
      degradation under anaerobic conditions. Presence of nitrate did not decrease the
      observed decolorization at the end of 24h SFABR cycle, although initial rate was
      decreased. This indicates the suitability of SFABR configuration for the
      treatment of azo-dye containing wastewaters in the presence of nitrate.

PMID- 17035004
TI  - Enhanced productivity of Chaetoceros calcitrans in airlift photobioreactors.
AB  - The various modes of cultivation of Chaetoceros calcitrans in airlift
      photobioreactors (ALPBRs) were examined. The batch system illustrated that the
      airlift configuration was superior to the bubble column as the airlift supported
      the circulation of the cell within the system, leading to a better light
      utilization. The cultivations in both semi-continuous and continuous systems
      resulted in a high cell productivity, although the steady state cell
      concentrations in both systems were lower than that obtained from the batch
      system. The behavior of the large-scale airlift system was not significantly
      different from the conventional bubble column where the diatom could only be
      produced at low cell density. Despite this, among all of the systems investigated
      in this work, the large-scale system gave the highest productivity. The main
      limiting factor for the large-scale airlift culture was the availability of
      light. Based on economical analysis, the continuous cultivation in the 2.8L ALPBR
      with a medium feed rate of 3 mL min(-1) was most attractive where the operation
      cost could be maintained at a minimum of approx. 7.95 x 10(-4)THBL(-1)h(-1).
      However, this continuous small-scale system still suffered from relatively low
      cell productivity (8.10 x 10(4)cellss(-1)).

PMID- 17035005
TI  - Efficiency of Penicillium chrysogenum PTCC 5037 in reducing low concentration of
      chromium hexavalent in a chromium electroplating plant wastewater.
AB  - The effectiveness of Penicillium chrysogenum was evaluated for reducing Cr(VI)
      from the wastewater of a chromium electroplating plant. Statistically-based
      experimental designs were applied to optimize the condition for reducing Cr(VI)
      to Cr(III). By applying Plackett-Burman factorial design and central composite
      design as the optimization step, attempts were made to identify optimal values of
      the three factors that bringing about maximum microorganism activity and
      therefore maximum hexavalent chromium(VI) bioreduction. It was found that each
      gram of P. chrysogenum of dry biomass condition could reduce 66 mg of Cr(VI) to
      Cr(III) in the wastewater of the chromium electroplating plant.

PMID- 17035006
TI  - The implication of Dichomitus squalens laccase isoenzymes in dye decolorization
      by immobilized fungal cultures.
AB  - The study focuses on the production of ligninolytic enzymes and dye degradation
      capacity of Dichomitus squalens immobilized on polyurethane foam (PUF) or pine
      wood (PW) in a fixed bed reactor at a laboratory scale (working volume of 0.6l).
      Immobilization of fungal cultures on pine wood improved eminently laccase
      production in comparison to the liquid cultures. Immobilized D. squalens was able
      to decolorize an anthraquinone dye Remazol Brilliant Blue R and an azo dye
      Reactive Orange 16, however, only a limited decolorization of
      Copper(II)phthalocyanine dye was observed in both types of reactor cultures. The
      involvement of a laccase activity in dye decolorization was suggested. Further,
      two different chromatographical forms of laccases, Lc1 and Lc2, were isolated
      from PW cultures of D. squalens using a fast, two step FPLC method. Enzymes
      revealed identical molecular masses of 68 kDa (estimated by SDS-PAGE) and similar
      pI's, however, they differed in their catalytic properties such as pH dependence
      of the activity and ABTS oxidation rates. In this study, we demonstrated
      different dye decolorization capacities of Lc1 and Lc2 as well.

PMID- 17035007
TI  - DNA sequence recognition in the minor groove by hairpin microgonotropens.
AB  - Two novel microgonotropens (MGTs) comprised of hairpin N-propylaminepyrrole
      polyamides linked to a Hoechst 33258 (Ht) analogue (3 and 4) were synthesized on
      solid phase by adopting an Fmoc technique using a series of HOBt mediated
      coupling reactions. The dsDNA-binding properties of MGTs 3 and 4 were determined
      by thermal denaturation experiments. Both MGTs were found to be selective for
      their nine-bp match dsDNA sequence 9 and were less tolerant of G/C bp
      substitutions in the binding region than linear progenitor MGT 1. MGT 3 was
      intolerant of a G/C substitution located in the middle of the binding region and
      did not bind to sequences 13 and 14. MGT 4 also did not bind to sequence 13, and
      its linker-bound Ht moiety was found to be more sensitive to a G/C substitution
      in the Ht-binding target, as demonstrated by the lack of binding to sequence 16.

PMID- 17035008
TI  - Synthesis of bisdesmosidic kryptogenyl saponins using the 'random glycosylation'
      strategy and evaluation of their antitumor activity.
AB  - A bisdesmosidic steroidal saponins library, composed of 16 novel kryptogenin
      glycosides, was set up via six random glycosylation procedures, wherein two
      compounds showed their antitumor activity against HeLa cell in the preliminary
      pharmacological research.

PMID- 17035010
TI  - N-Substituted carbazolyloxyacetic acids modulate Alzheimer associated gamma
      secretase.
AB  - N-Sulfonylated and N-alkylated carbazolyloxyacetic acids were investigated for
      the inhibition and modulation of the Alzheimer's disease associated gamma
      secretase. The introduction of a lipophilic substituent, which may vary from
      arylsulfone to alkyl, turned 2-carbazolyloxyacetic acids into potent gamma
      secretase modulators. This resulted in the selective reduction of Abeta(42) and
      an increase of the less aggregatory Abeta(38) fragment by several compounds
      (e.g., 7d and 8c). Introduction of an electron donating group at position 6 and 8
      of N-substituted carbazolyloxyacetic acids either decreased the activity or
      inversed modulation. The most active compounds displayed activity on amyloid
      precursor protein (APP) overexpressing cell lines in the low micromolar range and
      little or no effect on the gamma-secretase cleavage at the epsilon-site.

PMID- 17035009
TI  - Identification of a series of highly potent activators of the Nurr1 signaling
      pathway.
AB  - The nuclear receptor Nurr1 (NR4A2) is critically involved in the development and
      maintenance of midbrain dopaminergic neurons and is believed to function
      independently of endogenous activation. The hit identification and SAR studies
      leading to isoxazolo-pyridinone 7e, a highly potent, brain penetrable activator
      of the Nurr1 signaling pathway, are described.

PMID- 17035011
TI  - Screening of alpha-helical peptide ligands controlling a calcineurin-phosphatase
      activity.
AB  - In this paper, we describe an application of 202-membered fluorescently labeled
      peptide library designed to take an alpha-helix secondary structure. As a proof
      of-concept experiment, a calmodulin (CaM)/calcineurin (Cn) pair was chosen to
      screen alpha-helical peptide ligands that tightly bind to CaM and also control
      enzymatic functions of Cn. Three peptides were successfully selected from the
      library by assaying Cn-phosphatase activities and peptide-CaM interactions (dual
      check process). The strategy using a designed peptide library shows real promise
      as a peptide-based high-throughput screening system.

PMID- 17035012
TI  - ATP-conjugated peptide inhibitors for calmodulin-dependent protein kinase II.
AB  - Substrate analog peptides of CaMKII with varying degrees of the inhibitory
      potency were linked to ATPgammaS either by considering a phosphoryl transfer
      mechanism or simply by using a relatively long flexible linker. The latter
      bisubstrate inhibitors showed relatively little effects while the former ones
      improved inhibitory potency to different levels depending on the binding
      affinities of the peptide moieties. One of the mechanism-based bisubstrate
      inhibitors was then utilized to demonstrate an ATP-competitive but peptide
      substrate-uncompetitive inhibition, supporting an ordered binding mechanism for
      CaMKII.

PMID- 17035013
TI  - Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced
      antagonism to capsaicin.
AB  - Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation
      on the aromatic A-region to analyze their effects on potency and efficacy
      (agonism versus antagonism). The halogenation caused enhanced functional
      antagonism at TRPV1 compared to the corresponding prototype agonists. The
      analysis of SAR indicated that the antagonism was enhanced as the size of the
      halogen increased (I>Br>Cl) and when the 6-position was halogenated. Compounds
      23c and 31b were found to be potent full antagonists with K(i) (as functional
      antagonist)=23.1 and 30.3 nM in rTRPV1/CHO system, respectively.

PMID- 17035014
TI  - Intelligent fluorescent nucleoside in sensing cytosine base: importance of
      hydrophobic nature of perylene fluorophore.
AB  - Fluorescence response upon hybridization of perylene labeled oligonucleotide
      probes depends on the microenvironment experienced by the perylene fluorophore.
      In mismatched duplex ((Per)U-C), enhanced fluorescence was observed while in
      matched duplex ((Per)U-A) fluorescence intensity decreased considerably. This
      observation will be a promising research effort in giving rise to a new powerful
      tool in detection of SNP.

PMID- 17035015
TI  - Syntheses of F-18 labeled fluoroalkyltyrosine derivatives and their biological
      evaluation in rat bearing 9L tumor.
AB  - We hereby report the synthesis of four fluorine-18 labeled tyrosine derivatives,
      3-(2-[(18)F]fluoroethyl)tyrosine ([(18)F]1, [(18)F]ortho-FET), 3-(3
      [(18)F]fluoropropyl)tyrosine ([(18)F]2, [(18)F]ortho-FPT) O-methyl-[3-(2
      [(18)F]fluoroethyl)]tyrosine ([(18)F]3, [(18)F]MFET), and O-methyl-[3-(3
      [(18)F]fluoropropyl)]tyrosine ([(18)F]4, [(18)F]MFPT). The fluorine-18 labeled
      tyrosine derivatives were prepared by the displacement reaction of the ethyl and
      propyl tosylates with K[(18)F]/K2.2.2 in acetonitrile under no-carrier-added
      (NCA) conditions, followed by hydrolysis with 4N HCl. The biological properties
      of labeled compounds were evaluated in rats bearing 9L tumor after an intravenous
      injection and PET image was obtained. The tumor/blood and tumor/brain ratios were
      2.06, 2.92 for [(18)F]1, 2.25, 4.05 for [(18)F]2, 2.88, 1.90 for [(18)F]3, and
      2.00, 2.60 for [(18)F]4 at 60 min post injection, respectively. The PET image
      showed localized accumulation of PET tracers in 9L glioma of the rat.

PMID- 17035016
TI  - Glucose-specific poly(allylamine) hydrogels--a reassessment.
AB  - Polymer hydrogels synthesized by crosslinking poly(allylamine hydrochloride) with
      (+/-)-epichlorohydrin in the presence of d-glucose-6-phosphate monobarium salt do
      not show imprinting on the molecular level. A series of hydrogels was prepared
      using the following five templates: d-glucose-6-phosphate monobarium salt, d
      glucose, l-glucose, barium hydrogen phosphate (BaHPO(4)), and d-gluconamide; a
      hydrogel was also prepared in the absence of a template. For all six hydrogels,
      batch binding studies were conducted with d-glucose, l-glucose, d-fructose, and d
      gluconamide. The extent of analyte sugar binding was determined using (1)H NMR.
      Each hydrogel shows approximately the same relative binding affinity for the
      different sugar derivatives, and none displays selectivity for either glucose
      enantiomer. The results of the binding studies correlate with the octanol-water
      partition coefficients of the sugars, indicative that differential solubilities
      in the bulk polymer account for the binding affinities observed. Thus, in
      contrast to templated hydrogels prepared using methacrylate- or acrylamide-based
      reagents, true imprinting does not occur in this novel, crosslinked
      poly(allylamine hydrochloride) system.

PMID- 17035017
TI  - 2,6-Quinolinyl derivatives as potent VLA-4 antagonists.
AB  - A new series of 2,6-quinolinyl derivatives was prepared leading to potent low
      nanomolar VLA-4/VCAM-1 antagonists.

PMID- 17035018
TI  - Identification of novel, selective and potent Chk2 inhibitors.
AB  - A series of isothiazole carboxamidine compounds were synthesized and discovered
      as novel and selective inhibitors for Chk2. They are not active against the
      related Chk1 kinase. The structure-activity relationship studies were performed
      on the scaffold, and enzymatic kinetic analysis showed they are simple ATP
      competitive inhibitors with K(i) values as low as 11 nM for Chk2. Computer
      modeling studies were employed to comprehend the mechanism of action and SAR of
      these compounds.

PMID- 17035019
TI  - 4-Aminopyrimidines as novel HIV-1 inhibitors.
AB  - A series of 4-aminopyrimidines (1) was identified as novel HIV inhibitors of
      unknown molecular target. Structural modifications were carried out to establish
      its SAR and identify the linking site for target identification. A number of
      analogs were found to possess single digit inhibitory activity for HIV
      replication. Several analogs with various potential linkers, including a
      biotinated analog, also exhibited excellent potency, and could serve as tools for
      the identification of novel anti-HIV targets.

PMID- 17035020
TI  - Actin' together: serum response factor, its cofactors and the link to signal
      transduction.
AB  - The vast diversity of cellular types and behaviours is mainly the result of
      combinatorial interactions between a limited number of transcription factors and
      cellular signalling pathways whose activity is stringently controlled by
      developmental, cellular and extracellular cues. Studies of serum response factor
      (SRF) have provided a paradigm for such interactions for some years. Recent
      advances have shown that two families of SRF cofactors, the ternary complex
      factors (TCFs) and the myocardin-related transcription factors (MTRFs), are
      regulated by separate signalling pathways and thereby control SRF target genes
      differentially. The actin cytoskeleton is both an upstream regulator of MRTF
      activity, with monomeric actin directly acting as a signal transducer, and a
      downstream effector, because of the many cytoskeletal target genes. Here we
      discuss how the competition among cofactors might integrate these distinct
      signalling pathways into a specific transcriptional response and biological
      function.

PMID- 17035022
TI  - A method to standardize gait and balance variables for gait velocity.
AB  - Many gait and balance variables depend on gait velocity, which seriously hinders
      the interpretation of gait and balance data derived from walks at different
      velocities. However, as far as we know there is no widely accepted method to
      correct for effects of gait velocity on other gait and balance measures. We
      developed a simple statistical method to obtain gait and balance variables for
      each participant that are independent of gait velocity. The first step of our
      standardization method was the transformation of the gait and balance data to
      obtain a normal distribution and decrease the influence of outliers. Thereafter,
      we constructed a formula, based on regression analysis that described how these
      data varied with gait velocity in each participant during walking without an
      additional task. Last, this formula was used to standardize the gait and balance
      data for the effect of gait velocity for each individual participant. As example
      we present the analysis of mediolateral displacements of the trunk in fit elderly
      people during walking with and without a dual task.

PMID- 17035021
TI  - Effect of Tai Chi on gait and obstacle crossing behaviors in middle-aged adults.
AB  - This study investigated whether long-term, habitual practice of Tai Chi (or
      Taiji) results in behavioral modifications during gait. Specifically, we examined
      whether Tai Chi (TC) experience alters gait behavior during normal and obstructed
      walking. Fifteen experienced TC practitioners and fifteen control subjects
      (average age 45 years, 23-66 year range) completed level walking trials with or
      without a stationary obstacle placed in their path. TC practitioners in this
      study had an average of 6.5 years (1.5-15 year range) of Chen-style Tai Chi
      experience. Kinematic analyses performed on their step-to-step gait
      characteristics over multiple steps revealed that TC practitioners used a more
      cautious strategy by using slower gait speeds and shorter and slower steps than
      controls (p <or= 0.003). TC practitioners also spent significantly longer time in
      single leg support while crossing the obstacle (p < 0.001). The deleterious
      effect of this typically risky behavior may be mitigated in TC practitioners
      because of their comfort with single leg stance due to continual practice in this
      posture. It has been suggested that TC may reduce the risk of falls in older
      adults. Future studies will need to determine whether these observed gait
      behaviors are found in older adults and are related to reductions in fall risk.

PMID- 17035023
TI  - Selection and syntheses of tentacle type peptides as 'artificial' lectins against
      various cell-surface carbohydrates.
AB  - Sialyl Lewis X and its derivatives are cell-surface carbohydrates that are
      involved in cell-cell recognition by carbohydrate-mediated interactions.
      Unfortunately, owing to the similarities between carbohydrates only a limited
      number of tools are available for their differentiation. In this study, we
      prepared a selected phage-displayed peptide library against LeX (2), SLN (3), or
      LN (4), which compared to sLeX (1) lack sialic acid, fucose, and both sialic acid
      and fucose from constituents, respectively. Sequences of the selected peptides,
      prepared as tentacle type dimeric peptides, were prepared and shown to have
      micromolar affinities for the cognate carbohydrates. The specificities displayed
      by these 'artificial' lectins overwhelm those of natural lectins. These results
      suggest that they can serve as useful tools to detect changes in the terminal
      monosaccharide of cell-surface carbohydrates.

PMID- 17035026
TI  - Modifications of the pyroglutamic acid and histidine residues in thyrotropin
      releasing hormone (TRH) yield analogs with selectivity for TRH receptor type 2
      over type 1.
AB  - Thyrotropin-releasing hormone (TRH) analogs in which the N-1(tau) or the C-2
      position of the imidazole ring of the histidine residue is substituted with
      various alkyl groups and the l-pyroglutamic acid (pGlu) is replaced with the l
      pyro-2-aminoadipic acid (pAad) or (R)- and (S)-3-oxocyclopentane-1-carboxylic
      acid (Ocp) were synthesized and studied as agonists for TRH receptor subtype 1
      (TRH-R1) and subtype 2 (TRH-R2). We observed that several analogs were selective
      agonists of TRH-R2 showing relatively less or no activation of TRH-R1. For
      example, the most selective agonist of the series 13, in which pGlu is replaced
      with the pAad and histidine residue is substituted at the N-1 position with an
      isopropyl group, was found to activate TRH-R2 with a potency (EC(50)=1.9microM)
      but did not activate TRH-R1 (potency>100 microM); that is, exhibited >51-fold
      greater selectivity for TRH-R2 versus TRH-R1. Analog 8, in which pGlu is replaced
      with pAad and histidine is substituted at the N-1(tau) position with a methyl
      group, exhibited a binding affinity (K(i)=0.0032 microM) to TRH-R1 that is
      similar to that of [Ntau(1)-Me-His]-TRH and displayed potent activation of TRH-R1
      and TRH-R2 (EC(50)=0.0049 and 0.0024 microM, respectively). None of the analogs
      in which pGlu is replaced with the bioisosteric (R)- and (S)-(Ocp) and the
      imidazole ring is substituted at the N-1(tau) or C-2 position were found to bind
      or activate either TRH-R1 or TRH-R2 at the highest test dose of 100 microM.

PMID- 17035025
TI  - Synthesis of 6-chloroisoquinoline-5,8-diones and pyrido[3,4-b]phenazine-5,12
      diones and evaluation of their cytotoxicity and DNA topoisomerase II inhibitory
      activity.
AB  - The substituted chloroisoquinolinediones and pyrido[3,4-b]phenazinediones were
      synthesized, and the cytotoxic activity and topoisomerase II inhibitory activity
      of the prepared compounds were evaluated. Chloroisoquinolinediones have been
      prepared by the reported method employing 6,7-dichloroisoquinoline-5,8-dione. The
      cyclization to pyrido[3,4-b]phenazinediones was achieved by adding the aqueous
      sodium azide solution to the dimethylformamide solution of corresponding
      chloroisoquinoline-5,8-dione. The cytotoxicity of the synthesized compounds was
      evaluated by a SRB (Sulforhodamine B) assay against various cancer cell lines
      such as A549 (human lung cancer cell line), SNU-638 (human stomach cancer cell),
      Col2 (human colon cancer cell line), HT1080 (human fibrosarcoma cell line), and
      HL-60 (human leukemia cell line). Almost all the synthesized pyrido[3,4
      b]phenazinediones showed greater cytotoxic potential than ellipticine
      (IC(50)=1.82-5.97 microM). In general, the cytotoxicity of the pyrido[3,4
      b]phenazinediones was higher than that of the corresponding
      chloroisoquinolinediones. The caco-2 cell permeability of selected compounds was
      0.62 x 10(-6)-35.3 x 10(-6)cm/s. The difference in cytotoxic activity among
      tested compounds was correlated with the difference in permeability to some
      degree. To further investigate the cytotoxic mechanism, the topoisomerase II
      inhibitory activity of the synthesized compounds was estimated by a plasmid
      cleavage assay. Most of compounds showed the topoisomerase II inhibitory activity
      (28-100%) at 200 microM. IC(50) values for the most active compound 6a were 0.082
      microM. However, the compounds were inactive for DNA relaxation by topoisomerase
      I at 200 microM.

PMID- 17035024
TI  - Synthesis and evaluation of antitumor activity of novel N-acyllavendamycin
      analogues and quinoline-5,8-diones.
AB  - A series of 7-N-acyllavendamycins with zero, one or two substituents at the C-2',
      C-3', and C-11' were synthesized through short and efficient methods. Pictet
      Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with
      tryptamine or tryptophans produced the desired lavendamycins. Screening data on a
      panel of three ras oncogene-transformed cell lines and the non-transformed parent
      cell line showed that a significant number of these analogues are potent
      antitumor agents and appear to be particularly active against K-ras transformed
      cells. Compared with the corresponding quinolinediones, these novel lavendamycins
      are much more inhibitory toward the transformed cells indicating that the beta
      carboline moiety of the lavendamycin analogues plays an important role in its
      potency and selective toxicity.

PMID- 17035027
TI  - Apoptosis induction and modulation of P-glycoprotein mediated multidrug
      resistance by new macrocyclic lathyrane-type diterpenoids.
AB  - The macrocyclic lathyrane diterpenes, latilagascenes D-F (1-3) and jolkinol B
      (4), were isolated from the methanol extract of Euphorbia lagascae, and evaluated
      for multidrug resistance reversing activity on mouse lymphoma cells. All
      compounds displayed very strong activity compared with that of the positive
      control, verapamil. The structure-activity relationship is discussed. The
      evaluation of compounds 1 and 4, and of latigascenes A-C (5-7), isolated from the
      same species, as apoptosis-inducers was also carried out. Compound 1 was the most
      active. Furthermore, in the model of combination chemotherapy, the interaction
      between the doxorubicine and latilagascene B (6) was studied in vitro, on human
      MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction
      was synergistic. Latilagascenes D-F (1-3) are new compounds whose structures were
      established on the basis of spectroscopic methods, including 2D NMR experiments
      (COSY, HMQC, HMBC and NOESY).

PMID- 17035028
TI  - Structure of C-terminal fragment of merozoite surface protein-1 from Plasmodium
      vivax determined by homology modeling and molecular dynamics refinement.
AB  - One current vaccine candidate against Plasmodium vivax targeting asexual blood
      stage is the major merozoite surface protein-1 of P. vivax (PvMSP-1). Vaccine
      trials with PvMSP-1(19) and PvMSP-1(33) have succeeded in protecting monkeys and
      a large proportion of individuals, naturally exposed to P. vivax transmission,
      develop specific antibodies to PvMSP-1(19). This study presents a model for the
      three-dimensional structure of the C-terminal 19kDa fragment of P. vivax MSP-1
      determined by means of homology modeling and molecular dynamics refinement. The
      structure proved to be consistent with MSP-1(19) of known crystal or solution
      structures. The presence of a main binding pocket, well suited for protein
      protein interactions, was determined by CASTp. Corrections reported to the
      sequence of PvMSP-1(19) Belem strain were also inspected. Our model is currently
      used as a basis to understand antibody interactions with PvMSP-1(19).

PMID- 17035029
TI  - Synthesis and biophysical evaluation of minor-groove binding C-terminus modified
      pyrrole and imidazole triamide analogs of distamycin.
AB  - Five polyamide derivatives with rationally modified C-terminus moieties were
      synthesized and their DNA binding specificity and affinity determined. A
      convergent approach was employed to synthesize polyamides containing an
      alkylaminopiperazine (4 and 5), a truncated piperazine (6), or an alkyldiamino-C
      terminus moiety (7 and 8) with two specific objectives: to investigate the
      effects of number of potential cationic centers and steric bulk at the C
      terminus. CD studies confirmed that compounds 4, 5, 7, and 8 bind in the minor
      groove of DNA. The alkylpiperazine containing compounds (4 and 5) showed only
      moderate binding to DNA with DeltaT(m) values of 2.8 and 8.3 degrees C with their
      cognate sequence, respectively. The alkyldiamino compounds (7 and 8) were more
      impressive producing a DeltaT(m) of >17 and >22 degrees C, respectively. Compound
      6 (truncated piperazine) did not stabilize its cognate DNA sequence. Footprints
      were observed for all compounds (except compound 6) with their cognate DNA
      sequence using DNase I footprinting, with compound 7 producing a footprint of 0.1
      microM at the expected 5'-ACGCGT-3' site. SPR analysis of compound 7 binding to
      5'-ACGCGT-3', 5'-ACCGGT-3', and 5'-AAATTT-3' produced binding affinities of
      2.2x10(6), 3.3x10(5), and 1x10(5)M(-1), respectively, indicating a preference for
      its cognate sequence of 5'-ACGCGT-3'. These results are in good agreement with
      the footprinting data. The results indicate that steric crowding at the C
      terminus is important with respect to binding. However, the number of cationic
      centers within the molecule may also play a role. The alkyldiamino-containing
      compounds (7 and 8) warrant further investigation in the field of polyamide
      research.

PMID- 17035030
TI  - Structural advantage of dendritic poly(L-lysine) for gene delivery into cells.
AB  - This study aimed to investigate the relationships between structures of gene
      carrier molecules and their activities for gene delivery into cells. We compared
      2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6)
      and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA
      compaction level was weaker than that of PLL. The amount of DNA binding and
      uptake into cells mediated by PLL was 4-fold higher than that with KG6. However,
      KG6-mediated gene expression was 100-fold higher than that by PLL. Since pK(a)
      values of terminal amines of KG6 were lowered even though small amounts of DNA
      were internalized into cells, sufficient DNA amounts for effective gene
      expression escaped to the cytosol due to the proton sponge effect in the
      endosome. In addition, weakly compacted DNA with KG6 was advantageous in
      accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show
      the proton sponge effect in the endosome and resulted in strong compaction of
      DNA. Even though large DNA amounts were internalized into cells, most of the DNA
      would not take part in gene expression systems in the nucleus. Amount of induced
      cytokine production after intravenous injection of DNA complexes with KG6 and PLL
      was low, and was similar to the case when DNA was injected alone. Therefore, no
      significant difference in effects on cytokine production was observed between KG6
      and PLL.

PMID- 17035031
TI  - Role of glutamate 243 in the active site of 2-deoxy-scyllo-inosose synthase from
      Bacillus circulans.
AB  - 2-Deoxy-scyllo-inosose (DOI) synthase is involved in the biosynthesis of 2
      deoxystreptamine-containing aminoglycoside antibiotics and catalyzes the
      carbocyclic formation from d-glucose-6-phosphate (G-6-P) into DOI. The reaction
      mechanism is proposed to be similar to that of dehydroquinate (DHQ) synthase in
      the shikimate pathway, and includes oxidation of C-4, beta-elimination of
      phosphate, reduction of C-4, ring opening, and intramolecular aldol cyclization.
      To investigate the reaction mechanism of DOI synthase, site-directed mutational
      analysis of three presumable catalytically important amino acids of DOI synthase
      derived from the butirosin producer Bacillus circulans (BtrC) was carried out.
      Steady state and pre-steady state kinetic analysis suggested that E243 of BtrC is
      catalytically involved in the phosphate elimination step. Further analysis of the
      mutant E243Q of BtrC using substrate analogue, glucose-6-phosphonate, clearly
      confirmed that E243 was responsible to abstract a proton at C-5 in G-6-P and set
      off phosphate elimination. This glutamate residue is completely conserved in all
      DOI synthases identified so far and the corresponding amino acid of DHQ synthase
      is completely conserved as asparagine. Therefore, this characteristic glutamate
      residue of DOI synthase is a key determinant to distinguish the reaction
      mechanism between DOI synthase and DHQ synthase as well as primary sequence.

PMID- 17035032
TI  - Synthesis and characterization of styrylchromone derivatives as beta-amyloid
      imaging agents.
AB  - Several promising agents have been synthesized and evaluated for in vivo imaging
      probes of beta-amyloid plaques in Alzheimer's disease (AD) brain. Recently, we
      have developed flavone derivatives, which possess the basic structure of the 2
      phenylchromone, as useful candidates for amyloid imaging agents. In an attempt to
      further develop novel tracers, we synthesized and evaluated a series of 2
      styrylchromone derivatives, which replace the 2-phenyl substituent of flavone
      backbone with the 2-styryl. A series of radioiodinated styrylchromone derivatives
      were designed and synthesized. The binding affinities for amyloid plaques were
      assessed by in vitro binding assay using pre-formed synthetic Abeta(1-40)
      aggregates. The new series of styrylchromone derivatives showed high binding
      affinity to Abeta aggregates at the K(d) values of 32.0, 17.5 and 8.7nM for
      [(125)I]6, [(125)I]9, and [(125)I]12, respectively. In biodistribution studies
      using normal mice, [(125)I]6 and [(125)I]9 examined in normal mice displayed high
      brain uptakes with 4.9 and 2.8%ID/g at 2min post injection. The radioactivity
      washed out from the brain rapidly (1.6 and 1.0%ID/g at 60min post injection for
      [(125)I]6 and [(125)I]9, respectively). But [(125)I]12 did not show marked brain
      uptake, and the washout rate from the brain was relatively slow throughout the
      time course (1.1 and 1.4%ID/g at 2 and 30min post injection, respectively).
      Although additional modifications are necessary to improve the brain uptake and
      rapid clearance of non-specifically bound radiotracer, the styrylchromone
      backbone may be useful as a backbone structure to develop novel beta-amyloid
      imaging agents.

PMID- 17035033
TI  - Novel T-type calcium channel blockers: dioxoquinazoline carboxamide derivatives.
AB  - T-type calcium channel is one of therapeutic targets for the treatment of
      cardiovascular diseases and neuropathic pains. Since the withdrawal of
      mibefradil, a T-type calcium channel blocker, there have been a lot of efforts to
      develop T-type calcium channel blockers. A small molecule library of
      dioxoquinazoline carboxamide derivatives containing 155 compounds was designed,
      synthesized, and biologically evaluated for T-type calcium channel blocking
      activity. Among those compounds synthesized, the compound 1n shows the most
      potent T-type calcium current blocking activity with an IC(50) value of 1.52
      microM, which is comparable to that of mibefradil.

PMID- 17035034
TI  - Synthesis and biological evaluation of dihydrofuran-fused perhydrophenanthrenes
      as a new anti-influenza agent having novel structural characteristic.
AB  - Dihydrofuran-fused perhydrophenanthrenes were synthesized by means of o
      quinodimethane chemistry with high generality and stereoselectivity, and found to
      exhibit potent anti-influenza activity. These compounds exerted an inhibitory
      effect on various strains of influenza virus growth, including influenza A and B,
      with a concentration dependent manner, and direct cytotoxicity was low. Several
      biological experiments suggested that these new drugs affected a virus
      replication process before mRNA synthesis stage. Novel rigid cage-type of
      structural characteristic of the compounds has not been found in hitherto anti
      influenza drugs, and will provide new basis and motif for exploring promising and
      unprecedented anti-influenza agents.

PMID- 17035035
TI  - Green route for the heterocyclization of 2-mercaptobenzimidazole into beta-lactum
      segment derivatives containing -CONH- bridge with benzimidazole: Screening in
      vitro antimicrobial activity with various microorganisms.
AB  - The efficient and rapid synthesis of novel azetidin-2-ones 4a-j has been
      established. Thus, both microwave and conventional condensation 2-{(1H
      benzimidazol)-ylthio}-N'-2-(substituted phenyl) hydrazide with
      chloroacetylchloride were carried out in DMF-benzene solvent in the presence of
      Et(3)N catalyst. The microwave synthesis route afforded better yield with short
      time. The novel heterocycles were characterized by elemental analysis and
      spectral features. Some of the produced compounds were screened for their
      antimicrobial activity.

PMID- 17035037
TI  - Synthesis of diverse analogues of Oenostacin and their antibacterial activities.
AB  - Several diverse analogues of Oenostacin, a naturally occurring potent
      antibacterial phenolic acid derivative, have been synthesized. A small library
      with more than forty analogues having different aromatic rings and varied side
      chains has been achieved through solution phase synthesis. Some of these
      analogues, that is, 22, 23 and 42, possessed potent antibacterial activities
      against Staphylococcus epidermidis and Staphylococcus aureus having EC(50)
      ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM).

PMID- 17035036
TI  - Discovery of diphenyl amine based sodium channel blockers, effective against
      hNav1.2.
AB  - The development of new therapies for chronic pain is an area of unmet medical
      need. Central to pathways of chronic pain is the upregulation of voltage-gated
      sodium channels. The use of tricyclic antidepressants, which also have sodium
      channel activity, in chronic pain therapy prompted us to develop novel compounds
      from this scaffold. Herein, we show that the tricyclic moiety is not needed for
      effective inhibition of the [(3)H]-BTX binding site and sodium currents of
      hNa(v)1.2. Our lead compound 6, containing a diphenyl amine motif, demonstrated a
      53% inhibitory block of Na(v)1.2 currents at 10microM, which is greater than 50%
      increase in current block in comparison to the amitriptyline standard. Altogether
      our study establishes that the tricyclic motif is unnecessary for hNa(v)1.2
      activity and modification of the amine portion is detrimental to sodium channel
      block.

PMID- 17035038
TI  - Tri-, tetra- and heptacyclic perylene analogues as new potential antineoplastic
      agents based on DNA telomerase inhibition.
AB  - A recent approach in anticancer chemotherapy envisages telomerase as a
      potentially useful target. An attractive strategy deals with the development of
      compounds able to stabilize telomeric DNA in the G-quadruplex folded structure
      and, among them, a prominent position is found in the perylenes. With the aim to
      further investigate the role of drug structure, in view of possible
      pharmaceutical applications, we synthesized a series of compounds related to
      PIPER, a well-known perylene-based telomerase inhibitor. We modified the number
      of condensed aromatic rings and introduced different side chains to modulate drug
      protonation state and extent of self-aggregation. Effective telomerase inhibition
      was induced by heptacyclic analogues only, some showing a remarkably wide
      selectivity index with reference to inhibition of Taq polymerase. G-quadruplex
      stabilization was monitored by circular dichroism and melting experiments. Cell
      cytotoxicity measurements indicated a poor short-term cell killing ability for
      the best G-quartet binders. Besides the presence of a planar seven-condensed ring
      system, the introduction of a cyclic amine in the side chains critically affects
      the selectivity window.

PMID- 17035039
TI  - Morphological findings and energy dispersive X-ray microanalysis of oral amalgam
      tattoos.
AB  - Oral amalgam tattoos (AT) are distinct pigmentations of the oral mucosa resulting
      from accidental incorporation of dental amalgam in the oral soft tissues. Dental
      amalgams and in particular mercury, one of the constituents of dental amalgams,
      have for long been considered toxic. Oral ATs are easily accessible to study soft
      tissue reaction to amalgam and its degradation products. In this study, 17 oral
      ATs were examined by transmission electron microscopy and energy dispersive X-ray
      microanalysis. Ultrastructurally, in the ATs, three kinds of electron-dense
      particles were observed. The largest particles ranged in size from 0.5 up to
      several 100 microm. Smaller electron-dense inclusions (0.5-0.1 microm) were seen
      extracellularly associated with meshworks of elastic fibers and collagen bundles.
      The third and smallest type of particles (5-30 nm in diameter) was found with
      basement membranes of small vessels and pericytes and particularly decorating
      collagen bundles. Element analysis regularly revealed the presence of silver,
      sulphur, copper and lead in the AT decay products. Mercury was found in only one
      instance. Tissue reactions due to ATs seem to be minimal. No acute inflammatory
      changes were seen. Larger inclusions occasionally were surrounded by macrophages
      and multinucleated cells. TEM and element analysis may in specific cases be
      helpful in the differential diagnosis of pigmented lesions of the oral mucosa.

PMID- 17035040
TI  - A new digital autoradiographical method for identification of Pu particles using
      an imaging plate.
AB  - An autoradiographical method using an imaging plate (IP) was developed to
      identify rapidly the density of plutonium (Pu) particles on filter samples.
      Photostimulated luminescence (PSL) signals were obtained by exposing IPs to
      filter samples collecting Pu particles and naturally occurring radon decay
      products, respectively. Search and analysis of the alpha-induced PSL signals
      presented the time-dependent growth of PSL intensity from the Pu particles and
      the range of PSL intensities from radon decay products, making it possible to
      discriminate Pu particles from radon decay products using an empirical Pu
      discrimination level, and then to quantify the Pu activities on a particle-by
      particle basis. The method is useful for a fast screening of filter samples for
      Pu particles because it requires no special skills and tedious procedures during
      its use, gives a low discriminable activity for individual Pu particles with a
      relatively short exposure time, and allows us to measure a large number of filter
      samples at the same time.

PMID- 17035041
TI  - NANC inhibitory neuromuscular transmission in the hamster distal colon.
AB  - The neurotransmitter(s) that generate the inhibitory junctional potential (IJP)
      in the circular muscle of hamster distal colon and their mechanisms have not been
      elucidated. The aim of the present study, therefore, was to determine the
      contributing roles of the non-adrenergic, non-cholinergic (NANC) inhibitory
      transmitter(s) including nitric oxide (NO), adenosine 5'-triphosphate (ATP) and
      vasoactive intestinal polypeptide (VIP) in the generation of IJP in the hamster
      distal colon. For this purpose, the effects of the corresponding blockers of
      these putative NANC inhibitory mediators have been investigated using
      microelectrode technique. Intracellular membrane potential recordings were made
      from smooth muscle cells at 35 degrees C in Tyrode's solution that contained
      atropine (0.5microM), guanethidine (3microM) and nifedipine (0.5microM). Single
      electrical stimuli (0.5ms, 50V) as well as trains of two and five pulses (20Hz at
      the same duration and voltage) elicited NANC IJP consisted of initial fast (IJP
      F) followed by a slow hyperpolarization (IJP-S). The response had been abolished
      by tetrodotoxin (TTX, 0.3microM). The nitric oxide synthase (NOS) inhibitor, N(G)
      nitro-L-arginine methyl ester (L-NAME; 200microM) blocked IJP-S but enhanced IJP
      F. The later had been blocked with suramin, a universal P2 receptor antagonist,
      or with CBF3GA, a P2Y receptor antagonist at dose-dependent fashions. The IJP-F
      had been markedly inhibited by desensitization of P2Y receptor with its putative
      agonist 2-methylthio-ATP (2-meSATP, 50microM for 30min). IJP-F was sensitive to
      the P2Y1 receptor specific antagonist A3P5PS (10microM) and to the G-protein
      inhibitor, pertussis toxin (PTX, 400ng/ml for 2h) as well as to the small and
      intermediate Ca(2+) sensitive K(+) channels blocker, apamin (0.3microM). IJP-S
      was blocked by the guanylate cyclase (GC) inhibitor, 1H-[1,2,4]oxadiazolo-[4,3
      a]quinoxalin-1-one (ODQ, 10microM) and was partially sensitive to apamin.
      Exogenously applied ATP (100microM-1mM) produced typical hyperpolarization that
      was blocked by suramin, CBF3GA and 2-meSATP desensitization; while exogenously
      applied NO (3-10microM) produced slowly developing hyperpolarization that was not
      blocked by L-NAME but ODQ. In the presence of both purinergic and nitrergic
      inhibitors, stimulation using a train of eight pulses at 25Hz evoked a small slow
      hyperpolarization that was sensitive to the VIP antagonist (VIP 6-28, 1microM).
      Exogenous application of VIP (1-10microM) produced similar response that was not
      evident in the presence of VIP 6-28. These data indicate that NANC IJP that is
      generated in the circular muscle cells of hamster distal colon is mediated by ATP
      and NO via P2Y1/P2Y2 receptor and GC-dependent pathways, respectively. A masked
      role for VIP is also indicated.

PMID- 17035042
TI  - What immunologists should know about bacterial communities of the human bowel.
AB  - The human bowel is home to a bacterial community of much complexity. This article
      summarizes current bacteriological knowledge of the community and highlights
      topics of potential interest to innovative immunologists. The role of the
      bacterial community in the development and regulation of the immune system of
      neonates seems likely to be a particularly important area of future research.

PMID- 17035043
TI  - Induced expression of Olig2 is sufficient for oligodendrocyte specification but
      not for motoneuron specification and astrocyte repression.
AB  - To dissect out interactions between the transcription factor Olig2 and other
      intrinsic and extrinsic factors in neural cell fate determination, we established
      a mouse embryonic stem (ES) cell line with induced expression of Olig2 along
      neural differentiation. During neuronal differentiation, both the control and
      Olig2-induced groups produced a similar proportion of HB9-expressing motoneurons
      in the presence of retinoic acid (RA) and sonic hedgehog (SHH), but both
      generated few motoneurons in the absence of SHH. Induced Olig2 expression did not
      alter the pattern of gene transcription without SHH, suggesting that Olig2
      requires cooperation with RA and SHH for motoneuron specification. During glial
      differentiation, the Olig2-induced group generated significantly more
      oligodendrocytes and fewer neurons and astrocytes than the control group. This
      effect was not blocked by inhibition of SHH signaling, suggesting that Olig2
      bypasses the need of SHH in oligodendrocyte specification. However, treatment
      with ciliary neurotropic factor (CNTF) markedly increased astrocyte and decreased
      oligodendrocyte differentiation even when Olig2 is sustained in the nuclei,
      suggesting that Olig2 cannot bypass the CNTF-STAT signaling to repress astrocyte
      differentiation.

PMID- 17035044
TI  - Measuring pad-pad pinch strength in a non-human primate: Macaca fascicularis.
AB  - The primary purpose of this study was to establish a methodology for determining
      and perhaps predicting (via regression analysis of anthropometric measures)
      Macaca fascicularis isometric pinch strength for a specific task. The larger
      purpose of this work was to properly scale a pinching task for the monkeys in
      order to study dose-response relationships in a non-human primate model for
      carpal tunnel syndrome. Three female and one male macaque (n=4) of varying size
      and age were trained to perform a left-handed pad-pad pinch. The task required 60
      degrees of wrist flexion at a static pinching distance of 3 cm between the thumb
      and fingers. Subjects were trained for a period of 20-weeks. After that time, an
      analysis of performance gradients found that they had each reached a plateau in
      their force output. Pinch strength for the four animals ranged from 29.4 to 59.8
      N. Regression analysis revealed that body mass (kg) and wrist circumference (cm)
      were both predictive of pinch strength, exhibiting adjusted R(2) values of 0.93
      (p=0.024) and 0.96 (p=0.015), respectively. Thus, the results suggest that
      maximal pinch strength could be acceptably estimated in future subjects using
      either the wrist circumference or the body mass measures, as both were strong
      predictors of pad-pad pinch strength.

PMID- 17035045
TI  - EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap").
AB  - We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography
      (EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap
      ("InkCap") based on conductive ink technology. The InkCap was tested with
      temperature measurements on an electrically conductive phantom head and during
      structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at
      7 T. Combined EEG/fMRI measurements were conducted to study the interaction
      between the two modalities. The EEG recordings with the InkCap demonstrated up to
      a five-fold average decrease in signal variance during echo-planar imaging, with
      respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI
      measurements in human volunteers, alpha oscillations were clearly detected at 7
      T. Minimal artifacts were present in the T2* and high-resolution structural MR
      images of the brain parenchyma. Our results show that the InkCap technology
      considerably improves the quality of both EEG and (f)MRI during concurrent
      measurements even at 7 T.

PMID- 17035046
TI  - Implicit learning deficits in dyslexic adults: an fMRI study.
AB  - It is assumed that several neuropsychological impairments characterize the
      cognitive profile of individuals with developmental dyslexia (DD). Phonological
      and visual processing are often impaired as well as auditory processing,
      attention, and information processing speed. Although reports in the literature
      on implicit learning abilities are contradictory, recent neurological and
      physiological data suggest that these abilities are deficient in individuals with
      DD. To evaluate implicit learning we administered a classical version of the
      serial reaction time task (SRTT) related to sequence learning. Using functional
      magnetic resonance imaging we investigated brain activation patterns associated
      with implicit learning deficits in 14 adults with DD matched with 14 normal
      readers. SRTT results indicated the absence of implicit learning in the DD group
      and different activations between groups mainly in SMA, inferior parietal areas
      and cerebellar lobule 6. These results can be interpreted in the light of the
      different capacities for the two groups to build an internal model to guide
      movements. Further, they explain DD individuals' difficulty in domains not
      directly related to reading ability.

PMID- 17035047
TI  - Human brain glucose metabolism may evolve during activation: findings from a
      modified FDG PET paradigm.
AB  - In human brain, short-term physiological stimulation results in dramatic and
      proportional increase in blood flow and metabolic rate of glucose but minimal
      change in oxygen utilization, however, with continuing stimulation, we have
      observed that blood flow response diminishes and oxygen utilization increases.
      Given the temporal limitation of conventional methods to measure glucose
      metabolism in the human brain, we modified [(18)F]fluorodeoxyglucose (FDG) PET
      paradigm to evaluate the short-term and long-term effects of visual stimulation
      on human brain glucose metabolism. In the present study, seven healthy volunteers
      each underwent three dynamic FDG PET studies: at rest and after 1 min and 15 min
      of visual stimulation (using reversing black-white checkerboard) which continued
      for only 5 min after FDG injection. We found that increase in FDG uptake in the
      visual cortex was attenuated by 28% when preceded by 15 min of continuous visual
      stimulation (p<0.001). This decline in metabolism occurred in the absence of any
      behavior changes in task performance. The similarity in behavior of blood flow
      and glucose metabolism over time supports the hypothesis that, in activated
      brain, blood flow is modulated by changes in cytosolic free NADH/NAD(+) ratio
      related to increased glycolysis. Furthermore, the observed decline in glucose
      metabolism may reflect a shift from glycolytic to oxidative glucose metabolism
      with continued activation.

PMID- 17035048
TI  - Quantitative mapping of basal and vasareactive cerebral blood flow using split
      dose 123I-iodoamphetamine and single photon emission computed tomography.
AB  - A new method has been developed for diffusible tracers, to quantify CBF at rest
      and after pharmacological stress from a single session of dynamic scans with dual
      bolus administration of a radiotracer. The calculation process consisted of three
      steps, including the procedures of incorporating background radioactivity
      contaminated from the previous scan. Feasibility of this approach was tested on
      clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart,
      were carried out on each subject, after each of two split-dose administrations of
      111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the
      second IMP injection. Additional PET scans were also carried out on 6 subjects on
      a separate day, at rest and after acetazolamide administration. The other 5
      subjects were scanned only at rest during the whole study period. Quantitative
      CBF obtained by this method was in a good agreement with those determined with
      PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was
      approximately 40% over the whole cerebral area on healthy controls, which was
      consistent with a literature value. Reproducibility of CBF determined in the rest
      rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the
      second CBF, was reduced, providing reasonable image quality. Repeat assessment of
      quantitative CBF from a single session of scans with split-dose IMP is accurate,
      and may be applied to clinical research for assessing vascular reactivity in
      patients with chronic cerebral vascular disease.

PMID- 17035050
TI  - Effect of sodium valproate monotherapy on serum uric acid concentrations in
      ambulatory epileptic children: a prospective long-term study.
AB  - PURPOSE: Hyperuricemia has been shown to be related to cardiovascular morbidity
      and mortality. There is controversial data about the effect of sodium valproate
      (VPA) monotherapy on serum uric acid concentrations. The purpose of this study
      was to investigate by a long-term, prospective method, whether treatment with VPA
      monotherapy may alter serum uric acid concentrations and liver function tests in
      ambulatory epileptic children. MATERIAL AND METHODS: Serum uric acid
      concentrations were determined in 28 ambulatory epileptic children before and at
      6, 12 and 24 months of VPA monotherapy. Serum concentrations of biochemical
      markers of liver and renal function, such as alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma
      glutamyltransferase (gamma-GT) and creatinine (Cr) were also measured before and
      at 6, 12 and 24 months of VPA monotherapy. Serum VPA concentrations remained
      within the therapeutic range (50-100 mg/L) during the period of study. RESULTS:
      No statistically significant changes in serum uric acid concentrations were found
      at 6, 12 or 24 months of treatment. Serum ALT concentrations were significantly
      increased at 6 and 12 months of treatment, AST concentrations at 6 and 12 months
      of treatment and LDH concentrations at 12 months of treatment. CONCLUSIONS: VPA
      monotherapy does not have a significant effect on serum uric acid concentrations
      in ambulatory epileptic children. Further studies are needed to definitively
      address whether it would be useful for physicians to routinely check for elevated
      serum uric acid levels in children treated with VPA.

PMID- 17035049
TI  - 3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based
      morphometry.
AB  - 35% of HIV-infected patients have cognitive impairment, but the profile of HIV
      induced brain damage is still not well understood. Here we used tensor-based
      morphometry (TBM) to visualize brain deficits and clinical/anatomical
      correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis
      technique that uses fluid image warping, and a new alpha-entropy-based
      information-theoretic measure of image correspondence, called the Jensen-Renyi
      divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC
      stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+
      T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA
      copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were
      fluidly registered by applying forces throughout each deforming image to maximize
      the JRD between it and a target image (from a control subject). The 3D fluid
      registration was regularized using the linearized Cauchy-Navier operator. Fine
      scale volumetric differences between diagnostic groups were mapped. Regions were
      identified where brain atrophy correlated with clinical measures. RESULTS: Severe
      atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary
      and association sensorimotor areas. Atrophy of these regions, particularly in the
      white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T
      lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of
      AIDS neuropathology in living patients scanned with MRI. Severe atrophy in
      frontoparietal and striatal areas may underlie early cognitive dysfunction in
      AIDS patients, and may signal the imminent onset of AIDS dementia complex.

PMID- 17035051
TI  - Severe neurological complications in skeletal dysplasias: two case reports.
AB  - Skeletal dysplasias form a diverse and genetically heterogeneous group of
      disorders, but also share many clinical and radiographic features. We describe
      two illustrative cases and provide a short review of the literature on the
      neurological complications associated with various groups of skeletal dysplasias.
      These two cases illustrate that management of skeletal dysplasias requires a
      multidisciplinary approach, aimed at preventing or minimizing medical
      complications. Follow-up should include regular comprehensive neurological
      evaluation, as neurological complications can be severe and are often treatable
      if diagnosed at an early stage.

PMID- 17035052
TI  - Neuronal ceroid lipofuscinoses (NCL).

PMID- 17035054
TI  - Discovery of new potent human protein tyrosine phosphatase inhibitors via
      pharmacophore and QSAR analysis followed by in silico screening.
AB  - A pharmacophoric model was developed for human protein tyrosine phosphatase 1B (h
      PTP 1B) inhibitors utilizing the HipHop-REFINE module of CATALYST software.
      Subsequently, genetic algorithm and multiple linear regression analysis were
      employed to select an optimal combination of physicochemical descriptors and
      pharmacophore hypothesis that yield consistent QSAR equation of good predictive
      potential (r = 0.87,F-statistic = 69.13,r(BS)2 = 0.76,r(LOO)2 = 0.68). The
      validity of the QSAR equation and the associated pharmacophoric hypothesis was
      experimentally established by the identification of five new h-PTP 1B inhibitors
      retrieved from the National Cancer Institute (NCI) database.

PMID- 17035053
TI  - Anterior encephalocele associated with subependymal nodular heterotopia, cortical
      dysplasia and epilepsy: case report and review of the literature.
AB  - The presence of subependymal nodular heterotopia and cortical dysgenesis has been
      infrequently reported in patients with encephalocele. The majority of these
      patients were found to have posterior encephaloceles. We report a case of a
      Hispanic female with a frontoethmoidal encephalocele who developed epilepsy at 15
      years of age. Magnetic resonance imaging of the brain demonstrated left
      subependymal nodular heterotopia, partial agenesis of the corpus callosum and
      left fronto-temporal cortical dysplasia with polymicrogyria. This case
      illustrates the association of anterior encephalocele with subependymal nodular
      heterotopia, cortical dysplasia and epilepsy. It underscores the importance of
      screening for intracranial abnormalities in patients with anterior encephalocele.

PMID- 17035055
TI  - The molecular dynamics of assembly of the ubiquitous aortic medial amyloidal
      medin fragment.
AB  - In recent years there is an increased understanding of the molecular conformation
      of amyloid fibrils. However, much less is known about the early events that lead
      to the formation of these medically important assemblies. The clarification of
      these very important mechanistic details on the process may indicate directions
      towards the inhibition of the early stages of the assembly, where harmful species
      are most likely to form. Here, we study the dynamics of assembly of short
      amyloidogenic peptide fragments from the medin polypeptide. This polypeptide is
      of unique interest since amyloid deposits composed of medin are found almost in
      all the population above the age of 50. Twelve independent 50 ns long molecular
      dynamics simulations in explicit water have been run on peptide NH2-NFGSVQFV
      COOH, the minimal recognition hexapeptide element, NH2-NFGSVQ-COOH, and several
      single-point mutants. In all cases a three-stranded polymeric beta-sheet was used
      as the basic unit from which fibrils can be formed. Our results clearly indicate
      the need of well-defined sequence and stereochemical constraints to allow the
      formation of stable well-ordered aggregates. One of the key findings is the need
      for the presence of a phenylalanine residue, but not other hydrophobic amino
      acids, in specific positions within the peptide. Taken together, the results are
      consistent with recent high-resolution structures of amyloid assemblies and
      provide unique insights into the dynamics of these structures.

PMID- 17035056
TI  - Resveratrol alleviates bleomycin-induced lung injury in rats.
AB  - Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant
      balance such as pulmonary fibrosis. This study was designed to examine the
      effects of resveratrol, an antioxidant agents, against bleomycin-induced
      pulmonary fibrosis and oxidative damage. Wistar albino rats were administered a
      single dose of bleomycin (5 mg/kg; via the tracheal cannula) followed by either
      saline or resveratrol (10 mg/kg; orally) for 14 days. The effect of resveratrol
      on pulmonary oxidative damage was studied by cell count and analysis of cytokine
      levels (TGF-beta, TNF-alpha, IL-1beta and IL-6) in the bronchoalveolar lavage
      fluid (BALF) and biochemical measurements of malondialdehyde (MDA), an end
      product of lipid peroxidation; glutathione (GSH), a key antioxidant; and
      myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the lung
      tissue. Bleomycin-induced lung fibrosis was determined by lung collagen contents
      and also microscopically. Bleomycin caused a significant decrease in lung GSH,
      which was accompanied with significant increases in MDA level, MPO activity, and
      collagen contents of the lung tissue concomitant with increased levels of the pro
      inflammatory mediators and cell count in BALF. On the other hand, resveratrol
      treatment reversed all these biochemical indices as well as histopathological
      alterations induced by bleomycin. The results demonstrate the role of oxidative
      mechanisms in bleomycin-induced pulmonary fibrosis, and resveratrol, by its
      antioxidant properties, ameliorates oxidative injury and fibrosis due to
      bleomycin. Thus, an effective supplement with resveratrol as an adjuvant therapy
      may be a very promising agent in alleviating the side effects of bleomycin, an
      effective chemotherapeutic agent.

PMID- 17035057
TI  - Anoxia tolerance in turtles: metabolic regulation and gene expression.
AB  - Freshwater turtles of the Trachemys and Chrysemys genera are champion facultative
      anaerobes able to survive for several months without oxygen during winter
      hibernation in cold water. They have been widely used as models to identify and
      understand the molecular mechanisms of natural anoxia tolerance and the molecular
      basis of the hypoxic/ischemic injuries that occur in oxygen-sensitive systems and
      underlie medical problems such as heart attack and stroke. Peter L. Lutz spent
      much of his career investigating turtle anaerobiosis with a particular focus on
      the mechanisms of brain ion homeostasis and neurotransmitter responses to anoxia
      exposure and the mechanisms that suppress brain ion channel function and neuronal
      excitability during anaerobiosis. Our interests intersected over the mechanisms
      of metabolic rate depression which is key to long term anoxia survival. Studies
      in my lab have shown that a key mechanism of metabolic arrest is reversible
      protein phosphorylation which provides coordinated suppression of the rates of
      multiple ATP-producing, ATP-utilizing and related cellular processes to allow
      organisms to enter a stable hypometabolic state. Anoxia tolerance is also
      supported by selective gene expression as revealed by recent studies using cDNA
      library and DNA array screening. New studies with both adult T. scripta elegans
      and hatchling C. picta marginata have identified prominent groups of genes that
      are up-regulated under anoxia in turtle organs, in several cases suggesting
      aspects of cell function and metabolic regulation that have not previously been
      associated with anaerobiosis. These groups of anoxia-responsive genes include
      mitochondrially-encoded subunits of electron transport chain proteins, iron
      storage proteins, antioxidant enzymes, serine protease inhibitors, transmembrane
      solute carriers, neurotransmitter receptors and transporters, and shock proteins.

PMID- 17035058
TI  - Distribution and abundance of nutrient transporter mRNA in the intestinal tract
      of the black bear, Ursus americanus.
AB  - End products of digestion are absorbed by the body through the action of
      transporter proteins expressed on the apical membrane of intestinal epithelial
      cells. We investigated the mRNA abundance and distribution of a peptide
      transporter (PepT1), a glucose transporter (SGLT1), two amino acid transporters
      (NBAT and b(o,+)AT), and a digestive enzyme, aminopeptidase N (APN), in the
      intestinal tract of black bears (Ursus americanus). Intestinal total RNA was
      isolated from 10 bears and abundance of PepT1, SGLT1, NBAT, b(o,+)AT, and APN
      mRNA were determined by Northern blots. Abundance of PepT1 (P<0.05), APN
      (P<0.05), and SGLT1 (P<0.0001) changed quadratically from the proximal to distal
      intestine with abundance being greatest in the midregion. Abundance of b(o,+)AT
      mRNA increased linearly (P<0.05) from the proximal to distal intestine. The
      number of molecules of mRNA/ng of total RNA for each gene was determined using
      Real-Time PCR. PepT1 mRNA was present at 10-fold or greater levels than amino
      acid transporter mRNA in all segments of the intestine, suggesting that di- and
      tripeptides constitute a major form in which amino acids are absorbed in the
      black bear. The abundance of NBAT and b(o,+)AT mRNA was greater towards the
      distal intestine, suggesting a role in salvaging unabsorbed amino acids.

PMID- 17035059
TI  - IGF regulation of neutral amino acid transport in the BeWo choriocarcinoma cell
      line (b30 clone): evidence for MAP kinase-dependent and MAP kinase-independent
      mechanisms.
AB  - OBJECTIVE: IGF-1 and IGF-1 receptors are major determinants of fetal growth and
      are expressed primarily on the maternal-facing surface of the syncytiotrophoblast
      cell membrane in the human placenta. IGF-1 regulates fetal growth, in part, by
      regulating amino acid transport across the placenta. The objective of these
      studies was to study the role of IGF-1 and its signaling pathway in regulating
      neutral amino acid transport in a human trophoblast cell culture model. DESIGN:
      The regulation of neutral amino acid transport by IGF-1 was studied in cultured
      BeWo(b30) choriocarcinoma cells using the non-metabolizing amino acid analog,
      [(3)H]-alpha-aminoisobutyric acid (AIB). Transport in the absence of Na was used
      to distinguish system L from total AIB transport. Similarly, Na-dependent
      transport in the presence of excess methyl-AIB (MeAIB) permitted discrimination
      of systems A (MeAIB-sensitive) and ASC (MeAIB-insensitive). Specific inhibitors
      of intracellular signaling pathways were then used to determine the signaling
      pathway utilized by IGFs to regulate each amino acid transport system.
      Specificity of inhibition was assessed using specific markers of p70 S6 kinase
      activity and MAP kinase activation. RESULTS: Maximal stimulating concentrations
      of IGF-I (100 ng/ml) stimulated AIB transport by 30-40% exclusively through
      system A. Wortmannin (100 nM), an inhibitor of PI-3-kinase activity, inhibited
      all IGF-I-stimulated transport. Rapamycin (100 ng/ml), an inhibitor of p70 S6
      kinase, and bisindolylmaleimide, an inhibitor of protein kinase C (PKC), had no
      effect. PD-098059 (50 miccroM), an inhibitor of MAP kinase activation, inhibited
      20-30% of basal AIB transport but did not inhibit IGF-I-stimulated transport
      under the conditions studied. IGF-1 did not increase steady state mRNA levels of
      the system A transporters, SNAT1 and SNAT2, suggesting IGF-1 stimulates transport
      via post-transcriptional mechanisms. CONCLUSIONS: These data demonstrate that IGF
      I stimulates neutral amino acid transport system A by a PI3-kinase dependent,
      post-transcriptional pathway in the BeWo(b30) cell line. Additionally, system A
      activity appear to be sensitive to MAP kinase-dependent pathways not regulated by
      IGFs.

PMID- 17035060
TI  - [Lung cancer: is there a place for elective nodal irradiation?].
AB  - The use of conformal radiotherapy in lung cancer has considerably evolved with
      the advent of improved staging technologies and methods of radiation delivery.
      Patients with limited disease, inoperable for medical reasons, may be treated
      with conformal radiotherapy alone; patients with more advanced disease are
      treated with combined chemo-radiotherapy. If local control may be improved by
      radiotherapy dose escalation according to several studies, toxicity and more
      particularly pulmonary toxicity seems to be related to radiation volume. Thus the
      use of elective nodal irradiation is being questioned. Data for early stage
      (stage I) non-small-cell lung cancer treated with conformal radiotherapy or
      stereotactic hypofractionated radiotherapy strongly supports the use of smaller
      fields that do not incorporate elective nodal regions; local control and survival
      rates approach those of surgical series. In locally advanced non-small cell lung
      cancer, eliminating elective nodal irradiation allows to maximize tumor dose and
      minimize normal tissue toxicity in combined modality treatments; results are
      encouraging. The use of staging modalities such as positron emission tomography
      and eventually oesophageal ultrasonography is increasing, allowing to encompass
      the tumor volume with more accuracy. Several studies have confirmed that involved
      field irradiation results into a regional nodal rate of less than 10%. Further
      larger-scale studies would be needed to definitely establish "no elective nodal
      irradiation" as a standard in non-small cell lung cancer. There are very few data
      concerning small cell lung cancer.

PMID- 17035061
TI  - [Prostate localization systems for prostate radiotherapy].
AB  - The development of sophisticated conformal radiation therapy techniques for
      prostate cancer, such as intensity-modulated radiotherapy, implies precise and
      accurate targeting. Inter- and intrafraction prostate motion can be significant
      and should be characterized, unless the target volume may occasionally be missed.
      Indeed, bony landmark-based portal imaging does not provide the positional
      information for soft-tissue targets (prostate and seminal vesicles) or critical
      organs (rectum and bladder). In this article, we describe various prostate
      localization systems used before or during the fraction: rectal balloon,
      intraprostatic fiducials, ultrasound-based localization, integrated CT/linear
      accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D
      localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical
      benefit in using such prostate localization tools is not proven by randomized
      studies and the feasibility has just been established for some of these
      techniques. Nevertheless, these systems should improve local control by a more
      accurate delivery of an increased prescribed dose in a reduced planning target
      volume.

PMID- 17035062
TI  - Genetic determinants of acute inflammation regulate Salmonella infection and
      modulate Slc11a1 gene (formerly Nramp1) effects in selected mouse lines.
AB  - Two lines of mice selected to produce maximal (AIRmax) or minimal (AIRmin) acute
      inflammatory reactions (AIR) differ in their susceptibility to infection by
      Salmonella enterica serotype Typhimurium (S. Typhimurium). The LD(50) for AIRmax
      mice is 1000 times higher than that observed for AIRmin mice, and higher
      frequencies of Slc11a1 alleles (known to confer either resistance (R) or high
      susceptibility (S) to S. Typhimurium) were consistently found in AIRmax and
      AIRmin mouse lines, respectively. In order to evaluate the effect of the
      quantitative trait loci (QTL) segregated in AIRmax and AIRmin mice on Slc11a1
      dependent susceptibility to S. Typhimurium, the R and S alleles were fixed in
      homozygosity in AIRmax and AIRmin backgrounds by genotype assisted breedings.
      These new lines were named AIRmax(RR), AIRmax(SS), AIRmin(RR), and AIRmin(SS).
      Acute inflammation of Slc11a1(RR) animals was more severe in comparison to their
      Slc11a1(SS) counterparts, implicating Slc11a1 (or other linked genes) in AIR
      regulation. The LD(50) of S. Typhimurium was 800-times higher for AIRmax(SS) than
      for AIRmin(SS), demonstrating that AIR QTL can act as modifiers of the
      Slc11a1(SS) susceptibility gene. Four microsatellite markers for S. Typhimurium
      susceptibility QTL described in other mouse lines showed specific allele fixation
      in AIRmax or AIRmin mice, suggesting that these chromosomal regions also
      segregate with inflammatory phenotypes.

PMID- 17035063
TI  - Finite element modelling of the pelvis: inclusion of muscular and ligamentous
      boundary conditions.
AB  - Previous finite element studies of the pelvis, including subject-specific studies
      have made extensive simplifications with regards to the boundary conditions used
      during analysis. Fixed boundary conditions are generally utilised at the pubis
      and superior part of the ilium. While it can be demonstrated that these models
      provide a close match for certain in vitro experiments that use similar boundary
      conditions, the resulting stress-strain fields in the cortex in particular are
      unlikely to be those found in vivo. This study presents a finite element analysis
      in which the pelvis is supported by muscular and ligamentous boundary conditions,
      applied using spring elements distributed over realistic attachment sites. The
      analysis is compared to an analysis in which the pelvis is restrained by fixed
      boundary conditions applied at the sacro-iliac joints. Striking differences in
      the stress-strain fields observed in cortical bone in particular, are found
      between the two analyses. The inclusion of muscular and ligamentous boundary
      conditions is found to lower the occurrence of stress concentrations within the
      cortex.

PMID- 17035064
TI  - A control system for automatic electrical stimulation of abdominal muscles to
      assist respiratory function in tetraplegia.
AB  - People with tetraplegia have poor respiratory function leading to limited tidal
      volume (V(T)) and reduced cough peak flow (CPF). These problems may cause
      respiratory failure during the initial admission or subsequent intercurrent
      illness. Electrical stimulation of the abdominal muscles during expiration can
      improve respiratory function by increasing V(T) and CPF. We developed a novel
      control system to automatically trigger muscle stimulation, synchronised with the
      subject's voluntary respiratory activity. The system was tested in four subjects
      with a functionally complete lesion at level C4 to C6, aged between 16 and 46
      years, 3 months to 5 years post injury, who were breathing spontaneously. The
      algorithm delivered automatic stimulation patterns, detecting cough and quiet
      breathing while suppressing stimulation during other activities such as speaking.
      Marked increases in V(T) (between 9% and 71% of baseline) and CPF (between 31%
      and 54% of baseline) were observed, suggesting that the technique may have
      potential use in both acute and established tetraplegia to increase minute
      ventilation and to improve cough clearance of secretions.

PMID- 17035065
TI  - Preparation of microbubble suspensions by co-axial electrohydrodynamic
      atomization.
AB  - In this paper we report a novel method, based on co-axial electrohydrodynamic
      jetting, for the preparation of microbubble suspensions containing bubbles <10
      microm in size and having a narrow size distribution. No selective filtration is
      necessary and the suspensions are produced directly by the process. To
      demonstrate the method, glycerol was used as the liquid medium, flowing in the
      outer needle of the co-axial twin needle arrangement and undergoing
      electrohydrodynamic atomization in the stable cone-jet mode while air flowed
      through the inner needle at the same time. At zero applied voltage a hollow
      stream of liquid flowed from the outer needle. When the applied voltage was
      increased, eventually the hollow stream became a stable cone-jet and emitted a
      microthread of bubbles, which were collected in a container of glycerol to obtain
      microbubble suspensions. The size of the microbubbles was measured via optical
      microscopy and laser diffractometry. Several microbubble suspensions were
      prepared and characterised and the size distribution was found to be critically
      dependent on the ratio (n) of flow rates of liquid/air and, in particular the
      flow rate of the air. At n=1.5, with the flow rate of air set at approximately
      1.7 microl/s, a microbubble suspension containing bubbles in the size range 2-8
      microm was obtained.

PMID- 17035066
TI  - Adverse events and the vertebral artery: can they be averted?

PMID- 17035067
TI  - Gene expression profiling reveals complex changes following MEK-EE expression in
      cardiac myocytes.
AB  - The activation of the MEK/ERK pathway has been implicated in the proliferative
      growth of many tissues, however in the heart it has been linked with hypertrophic
      growth of the individual cardiac myocytes. We have explored the transcriptional
      consequences of prolonged ERK1/2 activation in cardiac myocytes following the
      adenoviral overexpression of a constitutively active form of MEK, MEK-EE.
      Analysis of microarray data obtained using full rat genome arrays showed >2000
      gene expression changes in response to MEK-EE overexpression for 24h. We observed
      similar numbers of genes upregulated and downregulated. The genes were involved
      in diverse processes including cell structure, metabolism and intracellular
      signalling. There were also changes in the pro- and ani-apoptotic genes as well
      as downregulation of the antioxidant enzymes, Mn superoxide dismutase, catalase
      and thioredoxin 2. Our results reveal the complexity of transcriptional changes
      that follow the activation of the ERK signalling pathway in these cells and
      suggest that activation of this MAPK pathway impinges on diverse cellular
      functions.

PMID- 17035068
TI  - Trafficking of osteonectin by retinal pigment epithelial cells: evidence for
      basolateral secretion.
AB  - Osteonectin is a glycoprotein that modulates several aspects of cellular
      behaviour including proliferation and adhesion. The retinal pigment epithelium
      forms a continuous monolayer of polarised cells immediately bellow the
      neuroretina, and is integral to the homeostasis of photoreceptor cells. While
      osteonectin is expressed by normal retinal pigment epithelium in situ, its
      expression is significantly increased in retinal pigment epithelial cells
      associated with several common retinal diseases. This pattern of expression
      implies an important role for osteonectin in the biology of retinal pigment
      epithelial cells. However, the trafficking, processing, and eventual fate of
      osteonectin in these cells is not clear at present. Although the theoretical
      report of a leader sequence within the osteonectin open reading frame and its
      extracellular presence in some tissues indirectly support secretion of the
      protein, there is no direct experimental demonstration of the secretion route to
      date. As a first step towards understanding the role of osteonectin in retinal
      pigment epithelium, we studied the intracellular distribution and trafficking of
      the protein in living cells. Here, we present experimental evidence that a
      precursor osteonectin fusion protein is targeted to the endoplasmic
      reticulum/Golgi pathway, with a likely basal secretion in retinal pigment
      epithelial cells. In addition, we show that the precursor osteonectin protein
      having the leader sequence masked fails to undergo secretion leading to cell
      death, a phenotype which may be of relevance not only for retinal pathology, but
      also for other diseases such as the bone disorder known as pseudoachondroplasia
      that is associated with a lack of osteonectin secretion.

PMID- 17035069
TI  - Photoperiodic control of flowering: not only by coincidence.
AB  - The timing of floral transition has a direct impact on reproductive success. One
      of the most important environmental factors that affect the transition is the
      change in day length (photoperiod). Classical experiments imply that plants
      monitor photoperiods in the leaf, and transmit that information coded within an
      elusive signal dubbed florigen to the apex to reprogram development. Recent
      advances in Arabidopsis research indicate that the core of the day-length
      measurement mechanism lies in the circadian regulation of CONSTANS (CO)
      expression and the subsequent photoperiodic induction of the expression of
      FLOWERING LOCUS T (FT) gene, which might encode a major component of florigen. In
      this review, we introduce current perspectives on how, when and where the floral
      signal is generated.

PMID- 17035070
TI  - NO signal at the crossroads: polyamine-induced nitric oxide synthesis in plants?
AB  - Polyamines, such as spermine, spermidine and putrescine, are ubiquitous
      polycationic compounds that are produced by almost all living organisms,
      including plants, animals, fungi and bacteria. Polyamines are multifunctional and
      interact with polyanionic biomolecules such as DNA or protein. However, despite
      their potential significance, the polyamine-dependent signal transduction system
      has not been revealed yet. Ni Ni Tun and colleagues have recently reported a
      possible linkage between polyamine and nitric oxide (NO), another ubiquitous
      signalling molecule.

PMID- 17035071
TI  - Futile cycling at the plasma membrane: a hallmark of low-affinity nutrient
      transport.
AB  - Plant nutrient acquisition from concentrated soil solutions is governed by low
      affinity transport systems in the plasma membranes of root cells. In this Opinion
      article, we illustrate that for six major nutrient ions, in addition to influx
      mediation by low-affinity transporters, high rates of ion cycling at the plasma
      membrane are a hallmark of nutrient transport at elevated external
      concentrations. This phenomenon is characterized by high rates of ion influx and
      concurrent high efflux of the same ion, resulting in efflux:influx ratios close
      to 1. Prolonged maintenance of futile cellular ion cycling can be energetically
      unfavorable and detrimental to plant growth and survival. We discuss how ion
      cycling can contribute to the toxicities of ions such as Na(+) and NH(4)(+) in
      the low-affinity range of ion provision. We also argue that cellular ion cycling
      makes the reliable measurement of ion influxes in the low-affinity range a
      formidable challenge.

PMID- 17035073
TI  - Interactions between macromolecules and ions: The Hofmeister series.
AB  - The Hofmeister series, first noted in 1888, ranks the relative influence of ions
      on the physical behavior of a wide variety of aqueous processes ranging from
      colloidal assembly to protein folding. Originally, it was thought that an ion's
      influence on macromolecular properties was caused at least in part by 'making' or
      'breaking' bulk water structure. Recent time-resolved and thermodynamic studies
      of water molecules in salt solutions, however, demonstrate that bulk water
      structure is not central to the Hofmeister effect. Instead, models are being
      developed that depend upon direct ion-macromolecule interactions as well as
      interactions with water molecules in the first hydration shell of the
      macromolecule.

PMID- 17035074
TI  - Unnatural base pair systems for DNA/RNA-based biotechnology.
AB  - The development of unnatural, extra base pairs could expand genetic information,
      by enabling the site-specific incorporation of functional components into nucleic
      acids and proteins. Researchers have been trying to create unnatural base pairs
      by drawing upon non-standard hydrogen-bonding topologies, shape complementarity,
      and/or hydrophobic interfaces, to confer sufficient selectivity and efficiency to
      work with the natural A-T(U) and G-C base pairs in replication, transcription and
      translation. The development of artificial genetic systems has been broadly
      advanced by combining the extra base pairs with modified natural components,
      including the base pairs, substrates and polymerase enzymes.

PMID- 17035075
TI  - Electron-conducting redox hydrogels: Design, characteristics and synthesis.
AB  - Redox hydrogels constitute the only electron-conducting phase in which water
      soluble chemicals and biochemicals dissolve and diffuse. The combination of
      solubility and diffusion makes the electron-conducting gels permeable to water
      soluble biochemicals and chemicals. The electron-conducting redox hydrogels serve
      to electrically connect the redox centers of enzymes to electrodes, enabling
      their use whenever leaching of electron-shuttling diffusional redox mediators
      must be avoided, which is the case in subcutaneously implanted biosensors for
      diabetes management and in miniature, potentially implantable, glucose-O2 biofuel
      cells. Because the hydrogels envelope the redox enzymes, they electrically wire
      the reaction centers to electrodes irrespective of spatial orientation and
      connect to electrode redox centers of multiple enzyme layers. Hence, the attained
      current densities of enzyme substrate electrooxidation or electroreduction are
      much higher than with enzyme monolayers packed onto electrode surfaces.

PMID- 17035076
TI  - Non-self recognition and programmed cell death in filamentous fungi.
AB  - Non-self recognition resulting in programmed cell death is a ubiquitous
      phenomenon in filamentous ascomycete fungi and is termed heterokaryon
      incompatibility (HI). Recent analyses show that genes containing predicted HET
      domains are often involved in HI; however, the function of the HET domain is
      unknown. Autophagy is induced as a consequence of HI, whereas the presence of a
      predicted transcription factor, VIB-1, is required for HI. Morphological features
      associated with apoptosis in filamentous fungi are induced by various stresses
      and drugs, and also during HI. Future analyses will reveal whether common or
      different genetic mechanisms trigger death by non-self recognition and death by
      various environmental onslaughts.

PMID- 17035077
TI  - A vibrational spectroscopic study of perhamite, an unusual silico-phosphate.
AB  - The silico-phosphate mineral perhamite has been studied using a combination of
      electron and vibrational spectroscopy. SEM photomicrographs reveal that perhamite
      morphology consists of very thin intergrown platelets that can form a variety of
      habits. Infrared spectroscopy in the hydroxyl-stretching region shows a number of
      overlapping bands which are observed in the range 3581-3078 cm(-1). These
      wavenumbers enable an estimation to be made of the hydrogen bond distances in
      perhamite: 3.176(0), 2.880(5), 2.779(6), 2.749(3), 2.668(1) and 2.599(7)A.
      Intense Raman bands are observed in the region 1110-1130 and 966-996 cm(-1) and
      are assigned to the SiO(4) and PO(4) symmetric stretching modes. Other bands are
      observed in the range 1005-1096 cm(-1) and are attributed to the nu(3)
      antisymmetric bending modes of PO(4). Some low intensity bands around 874 cm(-1)
      were discovered and remain unclassified. Bands in the low-wavenumber region are
      assigned to the nu(4) and nu(2) out-of-plane bending modes of the OSiO and PO(4)
      units. Raman spectroscopy is a useful tool in determining the vibrational
      spectroscopy of mixed hydrated multi-anion minerals such as perhamite.
      Information on such a mineral would be difficult to obtain by other means.

PMID- 17035078
TI  - A new spectrophotometric method for the determination of finasteride in tablets.
AB  - A simple, rapid, accurate, precise and sensitive colorimetric method for the
      determination of finasteride in tablets is described. The proposed methods are
      based on the formation of ion-pair complexes between the examined drug with
      bromophenol blue (BPB), bromocresol green (BCG) and bromothymol blue (BTB), which
      can be measured at the optimum lambda(max). Beer's law is obeyed in the
      concentration ranges 3.0-15.0, 3.0-15.0 and 5.0-20 microg/mL with BPB, BCG and
      BTB, respectively. The detection limits of FIN was found to be 1.16 microg/mL for
      BPB, 1.17 for BCG, 1.76 microg/mL for BTB. All the methods gave similar results
      and were validated for selectivity, linearity, precision and sensitivity. The
      proposed methods were directly and easily applied to the pharmaceutical
      preparation with accuracy, resulting from recovery experiments between 100.11 and
      100.33% for BPB, 100.17 and 100.67% for BCG and 100.33 and 100.60% for BTB
      methods. The low relative standard deviation values indicate good precision and
      high recovery values indicate accuracy of the proposed methods. The proposed
      methods have been applied to the determination of drug in commercial tablets.
      Results obtained from the analysis of commercial preparations with the proposed
      methods are in good agreement with those obtained with the official HPLC method.

PMID- 17035079
TI  - Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and
      acebutolol hydrochloride.
AB  - Simple and sensitive spectrophotometric and spectrofluorimetric methods are
      described for analysis of acyclovir and acebutolol hydrochloride. The proposed
      methods are based on oxidation of the selected drugs with cerium(IV) ion in
      acidic medium with subsequent measurement of either the decrease in absorbance at
      320nm or the fluorescence intensity of the produced cerous(III) ion at 361-363nm
      (excitation at 250nm). Beer's law obeyed from 2 to 8, 0.25 to 2.5microgcm-1
      acyclovir, 1 to 7 and 0.25 to 2.5microgml-1 acebutolol hydrochloride, using the
      spectrophotometric and spectrofluorimetric method, respectively. The proposed
      method were successfully applied for determination of the selected drugs in their
      pharmaceutical preparations with good recoveries.

PMID- 17035080
TI  - Design and implementation of an ICU incident registry.
AB  - Due to its complexity intensive care is vulnerable to errors. On the ICU adults
      of the AMC (Amsterdam, The Netherlands) the available registries used for error
      reporting did not give insight in the occurrence of unwanted events, and did not
      lead to preventive measures. Therefore, a new registry has been developed on the
      basis of a literature study on the various terms and definitions that refer to
      unintended events, and on the methods to register and monitor them. As this
      registry intends to provide an overall insight into errors, a neutral term
      ('incident') -- which does not imply guilt or blame -- has been sought together
      with a broad definition. The attributes of an incident further describe the
      unwanted event, but they should not form an impediment for the ICU nurses and
      physicians to report. The properties of a registry that contribute to making it
      accessible and user friendly have been determined. This has resulted in an
      electronic registry where incidents can be reported rapidly, voluntarily,
      anonymously and free of legal consequences. Evaluation is required to see if the
      new registry indeed provides the ICU management with the intended information on
      the current situation on incidents. For further refinement of the design,
      additional development and adjustments are required. However, we expect that the
      awareness of errors of the ICU personnel has already improved, forming the first
      step to increased patient safety.

PMID- 17035081
TI  - Is the genotyping of hepatitis B virus of clinical help in patient management?

PMID- 17035082
TI  - Umbilical cord blood screening for cytomegalovirus DNA by quantitative PCR.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection, which is the most common
      congenitally transmitted infection, affects approximately 1% of neonates
      worldwide. Despite its prevalence, no convenient screening test for neonatal CMV
      infection has been implemented. OBJECTIVE: The purpose of this pilot study was to
      evaluate the feasibility and yield of screening umbilical cord blood for CMV DNA
      emiaby quantitative PCR. STUDY DESIGN: Umbilical cord blood was tested for CMV
      DNAemia using a commercial quantitative PCR assay. Maternal CMV serostatus at the
      time of delivery was assessed by testing for CMV IgG and IgM antibodies in serum.
      CONCLUSIONS: Screening for congenital CMV infection with PCR is easily
      incorporated into routine labor and delivery care using discarded cord blood
      specimens to identify neonates whose infection is otherwise undiagnosed. Among
      433 infants tested, two (0.5%) had DNAemia detected in cord blood, one of whom
      was symptomatic, and both of whose mothers were CMV IgG positive and IgM
      negative. Viremic neonates identified by screening with PCR may be at high risk
      of developing long-term neurological complications of CMV infection and cannot
      reliably be identified using clinical presentation or maternal serology. Because
      of its convenience, cord blood CMV screening with PCR should be further
      investigated for incorporation into neonatal screening protocols.

PMID- 17035083
TI  - Non-indicated oral anticoagulation in left ventricular
      hypertrabeculation/noncompaction may jeopardize these patients.

PMID- 17035084
TI  - Polyethyleneterephthalate provides superior retention of endothelial cells during
      shear stress compared to polytetrafluoroethylene and pericardium.
AB  - BACKGROUND: Polyethyleneterephthalate (PET) and polytetrafluoroethylene (PTFE)
      are polymers successfully used as large diameter arterial grafts for peripheral
      vascular surgery. However, these prosthetic grafts are rarely used for coronary
      bypass surgery because of their low patency rates. Endothelialisation of the
      lumenal surface of these materials may improve their patency. This study aimed to
      compare the endothelialisation of PET, PTFE and pericardium by examining their
      seeding efficiency over time and the effect of various shear stresses on
      retention of endothelial cells. METHODS: Ovine endothelial cells at
      4x10(5)cells/cm(2) were seeded onto PET, PTFE and pericardium, and cultured for 1
      168 hours. Cell coverage was determined via en face immunocytochemistry and cell
      retention was quantified after being subjected to shear stresses ranging from
      0.018 to 0.037N/m(2) for 15, 30 and 60 minutes. RESULTS: Endothelial cells
      adhered to all of the materials one hour post-seeding. PET exhibited better cell
      retention rate, ranging from 66.9+/-5.6% at 0.018N/m(2) for 15min to 44.7+/-1.9%
      at 0.037N/m(2) for 60 minutes, when compared to PTFE and pericardium (p<0.0001,
      three-way ANOVA). CONCLUSION: PET shows superior retention of endothelial cells
      during shear stress compare to PTFE and pericardium.

PMID- 17035086
TI  - The origin and age of Plasmodium vivax.
AB  - The evolutionary history of Plasmodium vivax has recently been addressed in terms
      of its origin as a parasite of humans and the age of extant populations. The
      consensus is that P. vivax originated as a result of a host switch from a non
      human primate to hominids and that the extant populations did not originate as
      recently as previously proposed. Here, we show that, in a comparison of parasite
      isolates from across the world, Asian populations of P. vivax are the oldest. We
      discuss how this result, together with the phylogenetic evidence that P. vivax
      derived from Plasmodium found in Southeast Asian macaques, is most simply
      explained by assuming an Asian origin of this parasite. Nevertheless, the
      available data show only the tip of the iceberg. We discuss how sampling might
      affect time estimates to the most recent common ancestor for P. vivax populations
      and suggest that spatially explicit estimates are needed to understand the
      demographic history of this parasite better.

PMID- 17035087
TI  - Species accumulation curves and their applications in parasite ecology.
AB  - Species accumulation curves (SACs) chart the increase in recovery of new species
      as a function of some measure of sampling effort. Studies of parasite diversity
      can benefit from the application of SACs, both as empirical tools to guide
      sampling efforts and predict richness, and because their properties are
      informative about community patterns and the structure of parasite diversity.
      SACs can be used to infer interactivity in parasite infracommunities, to
      partition species richness into contributions from different spatial scales and
      different levels of the host hierarchy (individuals, populations and communities)
      or to identify modes of community assembly (niche versus dispersal). A historical
      tendency to treat individual hosts as statistically equivalent replicates
      (quadrats) seemingly satisfies the sample-based subgroup of SACs but care is
      required in this because of the inequality of hosts as sampling units. Knowledge
      of the true distribution of parasite richness over multiple host-derived and
      spatial scales is far from complete but SACs can improve the understanding of
      diversity patterns in parasite assemblages.

PMID- 17035088
TI  - Intestinal allergy expels hookworms: seeing is believing.
AB  - It is unclear how immunity limits hookworm infection. Australian researchers,
      using capsule and conventional gastrointestinal endoscopy in volunteers
      inoculated with Necator americanus, have reported that virtually all larvae reach
      the intestine within six weeks. Unlike the neutral response surrounding resident
      hookworms, newly arrived adults provoke an eosinophilic enteropathy. This
      allergic reaction curtails the attachment of hookworms and accompanies the
      passage of additional worms as they are expelled from the proximal small
      intestine.

PMID- 17035089
TI  - Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct
      mycobacteria growth indicator tube and phage amplified biological assay compared
      to BACTEC 460 TB.
AB  - The performance of antimycobacterial susceptibility testing for the first line
      drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria
      growth indicator tube (MGIT) and by bacteriophage amplified biological assay by
      FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system.
      This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN)
      smears. Sputum samples were subjected to culture and antimycobacterial
      susceptibility testing by BACTEC 460 TB. Samples were also tested by direct
      susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and
      streptomycine by MGIT. Sensitive and resistant isolates for RIF were further
      studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance
      pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or
      in combination with other drugs. Multiple drugs resistance was 20%. The agreement
      between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and
      ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST
      plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the
      sensitive strains. For majority of strains direct susceptibility tests were
      available within 6.34-6.404 days (95% confidence interval) with direct
      mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5
      11.5 days from the time that the sputum was received in the laboratory (95%
      confidence interval). From this study, we could conclude that direct MGIT AST is
      the quickest method for screening antimycobacterial susceptibility pattern for
      the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were
      available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for
      detection of rifampicin resistance after primary culture which can be used as a
      surrogate marker for presence of MDR strains and the results were available
      within 10.5-11.5 days.

PMID- 17035090
TI  - Salvaging of liquid-preserved O-positive and O-negative red blood cells by
      rejuvenation and freezing.
AB  - BACKGROUND: The RBC inventory is subject to seasonal highs and lows. When the
      inventory is high, units may be lost due to outdating and when the inventory is
      low, elective surgical procedures may have to be postponed until sufficient blood
      is available. This study was done to determine if universal donor O-positive and
      O-negative RBC subjected to various methods of transportation could subsequently
      be rejuvenated and frozen to be used for inventory control with satisfactory
      results. MATERIALS AND METHODS: Units of blood were collected at two different
      military facilities and processed as whole blood (WB) or packed RBC. The liquid
      stored WB or RBC units were subjected to transportation, with or without air
      dropping, as part of a military exercise. The units were kept at 4 degrees C with
      wet ice during transportation to the NBRL for evaluation. The quality of the
      liquid preserved RBC was evaluated before rejuvenation and freezing and after the
      freeze-thaw-wash procedure. Following frozen storage at -80 degrees C, the RBC
      were thawed and deglycerolized using the Haemonetics 115 cell washer. In addition
      to measurements of freeze-thaw and freeze-thaw-wash recovery, other in vitro
      assessments of RBC quality were made. RESULTS: The results demonstrate acceptable
      quality for RBC subjected to transportation, with or without air dropping,
      following rejuvenation and freezing. CONCLUSION: We consider it a prudent
      practice for liquid preserved O-negative and O-positive RBC collected at various
      blood collection sites to be sent to a specific facility where the universal
      donor RBC can be rejuvenated and frozen as a stockpile for inventory control.

PMID- 17035091
TI  - Release of PMN elastase, TGF-beta1 and neopterin during blood storage; unfiltered
      versus filtered blood.
AB  - Release of inflammatory mediators from blood cells during prestorage leukocyte
      filtration may result in recipient immune suppression. To investigate the effects
      of prestorage leukocyte filtration on the quality of blood components, twenty
      four blood units were collected from healthy donors and randomised into 3 groups.
      Eight units were stored as whole blood, eight units were separated into plasma,
      red blood cells (RBC) and buffy coat and eight units were collected and filtered
      through the ASAHI RZ 2000 leukocyte filter and separated into plasma and RBC. The
      units were stored for 35 days. Samples were collected weekly for analyses of
      polymorphonuclear elastase (PMN elastase), transforming growth factor-beta1 (TGF
      beta1) and neopterin. PMN elastase and neopterin increased during storage of
      whole blood and RBC. From the beginning and throughout storage, PMN elastase was
      increased in filtered plasma as compared with unfiltered plasma. Filtration per
      se did not influence the neopterin concentration in plasma or RBC. TGF-beta1
      increased in plasma and RBC during storage. In filtered plasma, an elevation of
      the TGF-beta1 concentration was observed from the start of storage. The TGF-beta1
      levels were higher in filtered plasma compared with unfiltered plasma. Prestorage
      leukocyte filtration increased the release of PMN elastase and TGF-beta1 in
      plasma and RBC.

PMID- 17035092
TI  - Expression of human liver HSPGs on acute myeloid leukemia.
AB  - Heparan sulfate proteoglycans (HSPGs) play important biological roles in cell
      matrix adhesion processes and are essential regulators of growth actions. The
      expression of the different HSPGs in itself is tightly regulated providing strict
      controls on the activities of the bound ligands. Human liver is a target for a
      number of pathogens, and HSPGs have been demonstrated in several cases to play a
      pivotal role in infectivity. Despite HSPGs important biological functions, little
      is known about its cell-specific distribution patterns. Human liver HSPG was
      isolated, and a specific monoclonal antibody (mAb) 1E4-1C2 was produced.
      Distribution of HSPG reactive to this mAb was studied in normal blood cells,
      hematopoietic cell lines and blood cells isolated from patients with various
      hematologic disorders using indirect immunofluorescence. There was no expression
      of molecules recognized by this mAb on lymphoid (Daudi, Jurkat, SupT-1) and
      monocytoid (U937) cell lines. Peripheral blood cells, normal bone marrow,
      together with leukocytes isolated from patients with acute lymphoblastic
      leukemia, chronic myelocytic leukemia, Hodgkin's disease or Non-Hodgkin's
      lymphoma, were also negative. In contrast, 1E4-1C2 showed significant positive
      results on human myeloid cell lines HL-60 and K562. Moreover, it is interesting
      that this mAb also recognized epitopes on leukocytes isolated from acute
      myeloblastic leukemia. These results suggest that malignancies of cells in
      myeloid lineage may cause expression of HSPGs that are detected by this specific
      mAb, making it a potential co-marker for the diagnosis of acute myeloid leukemia.

PMID- 17035093
TI  - Characterization of a cytotoxic CD57+ T cell subset from patients with pulmonary
      tuberculosis.
AB  - We investigated the proportion, phenotype, and cytotoxicity of CD8+CD57+ and CD57
      T cells in peripheral blood from 20 tuberculosis (TB)-patients and 20 healthy
      tuberculin skin test-positive donors. Our results showed an increase in CD8+CD57+
      T cells from TB-patients as compared with those from age-matched healthy donors
      (p<0.0001). CD8+CD57+ T cells from TB-patients expressed CD69, perforin, granzyme
      A, and a CD28-CD62L-CD161- phenotype without recognition for the alpha
      galactosylceramide-CD1d complex. This cell subset also expressed TNF-alpha and
      IFN-gamma, under phorbol-myristate-acetate/ionomycin stimulation. Interestingly,
      the cytotoxicity against autologous monocytes was higher in CD57- cells from TB
      patients and donors than their CD57+ counterparts, in the presence of
      Mycobacterium tuberculosis H37Rv culture filtrate. However, only CD8+CD57+ T
      cells from TB-patients exhibited spontaneous cytotoxicity against monocytes in
      the absence of antigen. Our results suggest that CD8+CD57+ T cells are a subset
      of effector cells that could be helpful to evaluate the cell-mediated immune
      response to M. tuberculosis.

PMID- 17035094
TI  - Murine experimental autoimmune gastritis models refractive to development of
      intrinsic factor autoantibodies, cobalamin deficiency and pernicious anemia.
AB  - Researchers have developed murine lymphopenic, non-lymphopenic, transgenic,
      spontaneous and infectious agent based models to induce an experimental
      autoimmune gastritis (EAG) for the study of human organ-specific autoimmune
      disease. These models result in a chronic inflammatory mononuclear cell
      infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells
      with autoantibodies reactive to the gastric parietal cells and the gastric H+/K+
      ATPase (ATP4), arguably hallmarks of a human autoimmune gastritis (AIG). In the
      case of AIG, it is well documented that, in addition to parietal cell antibodies
      being detected in up to 90% of patients, up to 70% have intrinsic factor
      antibodies with the later antibodies considered highly specific to patients with
      pernicious anemia. This is the first report specifically investigating the
      occurrence of intrinsic factor antibodies, cobalamin deficiency and pernicious
      anemia in EAG models. We conclude, in contrast to AIG, that, in the three EAG
      models examined, intrinsic factor is not selected as a critical autoantigen.

PMID- 17035095
TI  - Comparison of endothelial function in the carotid artery between normal and short
      term hypercholesterolemic rabbits.
AB  - The present study was undertaken to investigate and compare the vascular function
      in carotid arteries isolated from normal short-term hypercholesterolemic rabbits.
      Rabbits were fed normal or 0.5% cholesterol chow for 5 weeks. The tension of
      isolated carotid artery rings was measured isometrically. Serum lipid levels were
      measured and morphometric analysis was performed. And content of nitrate/nitrite
      in the carotid artery was also determined. In the carotid artery precontracted by
      phenylephrine, the cholesterol chow diet administered for 5 weeks decreased
      acetylcholine-induced relaxation at only middle concentrations, though it
      significantly increased the content of nitrate/nitrite, the sum of stable nitric
      oxide metabolites, in the carotid artery. Cholesterol chow for 5 weeks had no
      influence on sodium nitroprusside-induced relaxation in the carotid artery. The
      N(G)-nitro-L-arginine- and indomethacin-resistant endothelium-dependent
      relaxation induced by acetylcholine was significantly decreased in rabbits
      receiving the cholesterol chow as compared to rabbits receiving the control diet.
      The resistant part of acetylcholine-induced relaxation was significantly
      inhibited when the carotid artery was treated with glibenclamide, a selective
      inhibitor of ATP-sensitive K(+) channels, 4-aminopyridine, an inhibitor of
      voltage-dependent K(+) channels, or charybdotoxin, an inhibitor of large and
      intermediate conductance Ca(2+)-activated K(+) channels, and it was significantly
      inhibited by tetraethylammonium, a non-selective inhibitor of Ca(2+)-activated
      K(+) channels and N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF
      525a), a nonselective cytochrome P-450 monooxygenase (CYP) inhibitor, or
      ketoconazole, a selective CYP3A inhibitor in only normal rabbits. These results
      suggest that short-term hypercholesterolemia decreased EDHF-induced relaxation
      mediated through K(+) channels in rabbit carotid artery and that it may be due
      partially to the inhibition of CYP3A system in the carotid artery at an early
      stage of hypercholesterolemia.

PMID- 17035096
TI  - Effects of acute and prolonged naphthalene exposure on brain monoaminergic
      neurotransmitters in rainbow trout (Oncorhynchus mykiss).
AB  - We have shown previously that acute (1 to 6 h) and prolonged (1 to 5 days)
      exposure of rainbow trout to naphthalene resulted in decreased plasmatic cortisol
      and 17-beta-estradiol levels. In order to elucidate the mechanisms through which
      naphthalene might disrupt endocrine regulation, the present study investigated
      whether brain monoaminergic neurotransmitters are altered by the action of this
      polycyclic aromatic hydrocarbon. In a first experiment, immature rainbow trout
      were injected with vegetable oil alone or containing naphthalene (10 and 50
      mg/kg, i.p.), and sacrificed 1, 3 and 6 h after treatment. In a second
      experiment, slow-coconut oil implants alone or containing naphthalene (doses of
      10 and 50 mg/kg) were i.p. located and fish sacrificed 1, 3 and 5 days after
      treatment. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC),
      serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) were
      measured in several brain regions by HPLC. The results show that short-term
      naphthalene increases DA and 5-HT contents in hypothalamus and telencephalon, but
      differentially alter contents of the acid metabolites. Implants with naphthalene
      reduced DA content in hypothalamus and preoptic region but increased in
      telencephalon. 5-HT metabolism was decreased in hypothalamus, preoptic region,
      pituitary and brain stem after 3 to 6 days of treatment. In addition, the levels
      of NA were increased in hypothalamus and telencephalon after acute treatment and
      in hypothalamus and preoptic area after several days of exposure to naphthalene.
      These data suggest that brain neurotransmitter systems are sensitive to
      polycyclic aromatic hydrocarbons and could represent a target of the naphthalene
      induced neuroendocrine disruption.

PMID- 17035097
TI  - The yeast genome may harbor hypoxia response elements (HRE).
AB  - The hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor
      activated when cells are submitted to hypoxia. The heterodimer is composed of two
      subunits, HIF-1alpha and the constitutively expressed HIF-1beta. During normoxia,
      HIF-1alpha is degraded by the 26S proteasome, but hypoxia causes HIF-1alpha to be
      stabilized, enter the nucleus and bind to HIF-1beta, thus forming the active
      complex. The complex then binds to the regulatory sequences of various genes
      involved in physiological and pathological processes. The specific regulatory
      sequence recognized by HIF-1 is the hypoxia response element (HRE) that has the
      consensus sequence 5'BRCGTGVBBB3'. Although the basic transcriptional regulation
      machinery is conserved between yeast and mammals, Saccharomyces cerevisiae does
      not express HIF-1 subunits. However, we hypothesized that baker's yeast has a
      protein analogous to HIF-1 which participates in the response to changes in
      oxygen levels by binding to HRE sequences. In this study we screened the yeast
      genome for HREs using probabilistic motif search tools. We described 24 yeast
      genes containing motifs with high probability of being HREs (p-value<0.1) and
      classified them according to biological function. Our results show that S.
      cerevisiae may harbor HREs and indicate that a transcription factor analogous to
      HIF-1 may exist in this organism.

PMID- 17035098
TI  - Acclimatable cardiac and ventilatory responses to copper in the freshwater
      crayfish Procambarus clarkii.
AB  - Mortality and physiological tests following exposure to waterborne copper were
      performed in the red swamp crayfish Procambarus clarkii from a central Italian
      population. Mortality tests gave an estimated 96 h LC50 value (with 95%
      confidence limits) of 162 (132-211) mg L(-1) waterborne copper II. Variations in
      cardiac and ventilatory rates were simultaneously monitored using a non-invasive
      plethysmographic technique. In experiments with different sub-lethal copper
      concentrations (control, 0.5, 1 and 10 mg L(-1)) performed at different times (3,
      6, 96 h), copper exposure elicited a reduction in both heart and scaphognatite
      rates. Following exposure to 10 mg L(-1) copper for 96 h, the heart and
      scaphognatite rates decreased to about 35% of the initial values. The reduction
      was fully reversible, since crayfish exposed to 0.5, 1 and 10 mg Cu L(-1) for 96
      h resumed control rates after a 3-h residence in clean water. In crayfish pre
      exposed (96 h) to sub-lethal copper concentrations (0.1 and 1 mg L(-1)) and then
      held in control water (3 h), the reduction of heart and scaphognatite rates after
      exposure to 10 mg Cu L(-1) were significantly lower than in specimens pre-exposed
      to control water. Therefore, copper induces a concentration and time dependent
      reduction of both cardiac and ventilatory activity in P. clarkii; these responses
      can be reduced or fully abolished by pre-exposure to sub-lethal levels of the
      metal.

PMID- 17035099
TI  - Antioxidant protection and plasma carotenoids of incubating great tits (Parus
      major L.) in relation to health state and breeding conditions.
AB  - Carotenoids are biologically active pigments, which are important for animals due
      to their dual role in health maintenance and ornamental signalling. In adult
      birds, immunostimulatory properties of carotenoids have been repeatedly
      demonstrated while much less is known about the importance of carotenoids as
      antioxidants. We studied the relationships between plasma carotenoid levels, as
      well as total antioxidant protection, and various hemato-serological health state
      indices in female great tits (Parus major L.), incubating their second clutches
      in two contrasting (coniferous and deciduous) habitats in southwest Estonia. To
      manipulate reproductive effort, four eggs were removed from half of the clutches
      during laying to stimulate females to lay additional eggs. However, egg removal
      had no effect on the final number of eggs laid. Plasma carotenoid levels
      increased seasonally in parallel with caterpillar food availability. However, no
      between-habitat differences in carotenoid levels, total antioxidant capacity, or
      indices of health state could be found despite the apparently better feeding
      conditions in the coniferous habitat. No correlation was detected between plasma
      carotenoid levels and measures of total antioxidant capacity, which suggests that
      at least for the adult birds feeding on naturally carotenoid-rich diet,
      antioxidant function of carotenoids is not of primary importance. A strong non
      linear association between the measures of antioxidant protection and leukocytic
      markers of inflammation was found, which suggests that measures of total
      antioxidant capacity deserve further attention in ecophysiological studies as
      potential indicators of immunopathology.

PMID- 17035100
TI  - Isolation and expression of zebrafish zinc-finger transcription factor gene tsh1.
AB  - We report the expression patterns of tsh1, a zebrafish homologue of the
      Drosophila homeotic gene teashirt. Expression of tsh1 is first detected at the 2
      somite stage (10h post-fertilization, hpf) at the anterior end of the spinal
      cord. Expression expands toward the posterior spinal cord, and by the prim-5
      stage (24 hpf) tsh1 transcripts are detected throughout spinal cord. Between the
      14- and 25-somite stage (16-24 hpf), spinal cord expression shows a clear
      anterior boundary at the rostral margin of rhombomere 7. Around the prim-25 stage
      (36 hpf), while the spinal expression of tsh1 decreases, new expression is
      detected in the pectoral fin buds and dorsal forebrain. By the long-pec stage (48
      hpf), spinal cord expression is undetectable, but strong expression is observed
      in the rhombencephalon, telencephalon, tectum opticum, midbrain-hindbrain
      boundary, in the first pharyngeal arch and in the eyes. This expression persists
      at least until the larval stages. Retinoic acid signaling influences tsh1
      expression. Zebrafish tsh1 expression was induced in the anterior neural tube in
      embryos treated briefly with exogenous retinoic acid. Furthermore, tsh1
      expression was down-regulated in the spinal cord in the zebrafish neckless mutant
      in which RA signaling is disrupted due to a missense mutation in the gene
      encoding retinaldehyde dehydrogenase type 2.

PMID- 17035101
TI  - Dynamic expression of R-spondin family genes in mouse development.
AB  - R-spondins (Rspo) are a recently discovered secretory protein family with four
      members in human and mouse. We and others demonstrated that R-spondins can
      activate canonical Wnt signaling and beta-catenin-dependent gene expression. Our
      study further demonstrated that R-spondins are novel ligands for the Frizzled8
      and LRP6 (LDL-receptor-related protein 6) receptors. To gain insight into their
      biological functions, the RNA expression pattern of the mouse R-spondin family
      genes was analyzed during mouse development. Our study shows that R-spondin gene
      transcripts are widely expressed with distinct patterns in mouse at different
      developmental stages.

PMID- 17035102
TI  - Yeast Rev1 is cell cycle regulated, phosphorylated in response to DNA damage and
      its binding to chromosomes is dependent upon MEC1.
AB  - Translesion DNA synthesis (TLS) is one of the mechanisms involved in lesion
      bypass during DNA replication. Three TLS polymerases (Pol) are present in the
      yeast Saccharomyces cerevisiae: Pol zeta, Pol eta and the product of the REV1
      gene. Rev1 is considered a deoxycytidyl transferase because it almost exclusively
      inserts a C residue in front of the lesion. Even though REV1 is required for most
      of the UV-induced and spontaneous mutagenesis events, the role of Rev1 is poorly
      understood since its polymerase activity is often dispensable. Rev1 interacts
      with several TLS polymerases in mammalian cells and may act as a platform in the
      switching mechanism required to substitute a replicative polymerase with a TLS
      polymerase at the sites of DNA lesions. Here we show that yeast Rev1 is a
      phosphoprotein, and the level of this modification is cell cycle regulated under
      normal growing conditions. Rev1 is unphosphorylated in G1, starts to be modified
      while cells are passing S phase and it becomes hyper-phosphorylated in mitosis.
      Rev1 is also hyper-phosphorylated in response to a variety of DNA damaging
      agents, including treatment with a radiomimetic drug mostly causing double-strand
      breaks (DSB). By using the chromosome spreading technique we found the Rev1 is
      bound to chromosomes throughout the cell cycle, and its binding does not
      significantly increase in response to genotoxic stress. Therefore, Rev1
      phosphorylation does not appear to modulate its binding to chromosomes,
      suggesting that such modification may influence other aspects of the TLS process.
      Rev1 binding under damaged and undamaged conditions, is at least partially
      dependent on MEC1, a gene playing a pivotal role in the DNA damage checkpoint
      cascade. This genetic dependency may suggest a role for MEC1 in spontaneous
      mutagenesis events, which require a functional REV1 gene.

PMID- 17035103
TI  - Solid phase proteomics: dramatic reinforcement of very weak protein-protein
      interactions.
AB  - Very weak protein-protein interactions may play a critical role in cell
      physiology but they are not easily detectable in "in vitro" experiments. To
      detect these weak interactions, we have developed a strategy that included: (a)
      design of a rapid and very effective crosslinking of protein-protein complexes
      with poly-functional reagents; (b) selective adsorption of very large proteins on
      lowly activated ionic exchangers, based on the need of a multipoint physical
      adsorption to incorporate the proteins into the matrix; (c) purification by
      selective adsorption of protein-protein complexes formed by strong protein
      protein interactions, via selective adsorption of the complexes on lowly
      activated ionic exchangers via multi-protein physical adsorption and leaving the
      non-associated proteins in the solution; (d) reinforcement of very weak protein
      protein interactions by selective adsorption of the complex on lowly activated
      ionic exchange supports via a synergetic cooperation of the weak protein-protein
      interaction plus the interactions of both proteins with the support enabling the
      almost full shifting of the equilibrium towards the association position; (e)
      control of the aggregation state of proteins like BSA, formed by weak protein
      protein interactions. In this last case, it seems that the interaction of the
      protein molecules placed on the borders of the aggregate with the groups on the
      support partially stabilizes the whole aggregate, although, some molecules of the
      aggregate cannot interact with the support. The size of the aggregates may be
      defined by controlling the concentration of ionised groups on the support: the
      less activated the supports are, the bigger the complexes. In this way, solid
      phase proteomics could be a very interesting tool to detect weak protein-protein
      interactions.

PMID- 17035104
TI  - Detection of S-nitrosothiols in biological fluids: a comparison among the most
      widely applied methodologies.
AB  - Many different methodologies have been applied for the detection of S
      nitrosothiols (RSNOs) in human biological fluids. One unsatisfactory outcome of
      the last 14 years of research focused on this issue is that a general consensus
      on reference values for physiological RSNO concentration in human blood is still
      missing. Consequently, both RSNO physiological function and their role in disease
      have not yet been clarified. Here, a summary of the values measured for RSNOs in
      erythrocytes, plasma, and other biological fluids is provided, together with a
      critical review of the most widely used analytical methods. Furthermore, some
      possible methodological drawbacks, responsible for the highlighted discrepancies,
      are evidenced.

PMID- 17035105
TI  - A general method for the extraction of citrus leaf proteins and separation by 2D
      electrophoresis: a follow up.
AB  - With the aim of studying differentially expressed proteins as a function of
      abiotic and biotic stress in citrus plants, we optimized a protocol for the
      extraction of total leaf proteins and their 2-DE separation using commercially
      available immobilized pH gradient strips (IPGs) in the first dimension. Critical
      factors for good reproducibility of citrus leaf protein separation were
      identified: trichloroacetic acid (TCA)/acetone precipitation after extraction in
      lysis buffer, sample fractionation on narrow range overlapping IPGs and sample
      cup loading at the anodic or cathodic end of the strip. The use of thiourea and a
      strong detergent (C7BzO) in the solubilization/rehydration buffer, coupled with
      the increase to 10% of SDS in the equilibration buffer before the second
      dimension seemed to affect positively the resolution of basic proteins. Using our
      protocol we resolved about 30 basic proteins on 6.3-8.3 pH range strips. Further,
      our protocol was successfully applied reproducibly on the analysis of control and
      salt exposed leaf samples of Citrus reshni Hort. Ex Tan.

PMID- 17035106
TI  - Efficient and scalable method in isolation of polymethoxyflavones from orange
      peel extract by supercritical fluid chromatography.
AB  - Polymethoxyflavones (PMFs) from citrus genus are of particular interest because
      of their broad spectrum of biological activities, such as anti-inflammatory, anti
      carcinogenic, and anti-atherogenic properties. Recently, the exploration into the
      beneficial health properties of PMFs in citrus fruits has dramatically increased.
      However, the supply of pure PMFs in the in vivo study is a limiting factor due to
      the difficulties in large-scale isolation of the interested PMFs. Therefore, the
      development of an efficient and a scalable separation method of PMFs is necessary
      and significant. In this paper, we report a newly developed method for efficient
      and relatively large-scale isolation of four PMFs from sweet orange (Citrus
      sinensis) peel by employing supercritical chromatography (SFC): nobiletin,
      tangeretin, 3,5,6,7,8,3',4'-heptamethoxyflavone and 5,6,7,4'-tetramethoxyflavone.

PMID- 17035107
TI  - Current methods for phosphoprotein isolation and enrichment.
AB  - The phosphorylation of proteins is a central paradigm of signal transduction. The
      substitution of neutral hydroxyl groups of serine, threonine and tyrosine with a
      negatively charged phosphate group alters the physicochemical and immunogenic
      properties of the protein, which then can be used to isolate these isoforms. In
      the last decades several different techniques were applied, attempting to
      selectively enrich protein populations with this post-translational modification.
      This review aims to give an overview on the arsenal of available methods to
      extract phosphoproteins focusing on chromatographic approaches.

PMID- 17035108
TI  - Contribution of W229 to the transglycosylation activity of 4-alpha
      glucanotransferase from Pyrococcus furiosus.
AB  - A W229H mutant of 4-alpha-glucanotransferase (4-alpha-GTase) from Pyrococcus
      furiosus was constructed and its catalytic properties were studied to investigate
      the role of W229 in the catalytic specificities of the enzyme. Various activities
      and kinetic parameters were determined for the wild-type and W229H mutant
      enzymes. The transglycosylation factor and transglycosylation activity of the
      mutant enzyme markedly decreased, but its hydrolysis activity was scarcely
      affected. It was discovered that the k(cat)/K(m) value of transglycosylation
      activity significantly decreased to about 15% of that of the wild type, while
      k(cat)/K(m) value of hydrolysis activity changed little for the mutant enzyme.
      The hydrophobicity of W229 was thought to be critical to the transglycosylation
      activity of the enzyme based on the enzyme's modeled tertiary structures.

PMID- 17035109
TI  - Protein processing and other modifications analyzed by diagonal peptide
      chromatography.
AB  - Diagonal peptide chromatography consists of two consecutive, identical peptide
      separations with in between an enzymatic or chemical alteration of the side-chain
      structure of selected peptides. Such selected and altered peptides acquire
      different chromatographic properties thereby segregating from non-altered
      peptides in a series of secondary peptide separations. Originally described by
      Brown and Hartley in 1966, we have modified the technique such that it can be
      used for higher throughput gel-free proteomics. Our technique is termed COmbined
      FRActional DIagonal Chromatography (COFRADIC) and exploits evoked differences of
      the hydrophobicity of peptides in reverse-phase liquid chromatography. One
      important advantage of COFRADIC is its versatility: by changing the alteration
      reaction, different classes of peptides are sorted and finally analyzed. We
      previously published protocols and applications for separating methionyl,
      cysteinyl, amino terminal and phosphorylated peptides. In this review, we assess
      the potential of COFRADIC for the analysis of several posttranslational
      modifications emphasizing on in vivo protein processing events. Additional
      modifications that can be analyzed include phosphorylation and N-glycosylation.
      The potential of COFRADIC for isolating peptides holding such modified amino
      acids are discussed here.

PMID- 17035110
TI  - GERD and interstitial lung disease. Cause, effect, or true true and unrelated?

PMID- 17035111
TI  - Sexual dimorphism affects tibia size and shape but not tissue-level mechanical
      properties.
AB  - Understanding how growth influences adult bone morphology and tissue quality
      should provide important insight into why females show a greater incidence of
      stress fractures early in life and fragility fractures later in life compared to
      males. The objective of this study was to test whether females acquire similar
      tissue-level mechanical properties as males by the time peak bone properties are
      established. Standardized beams of bone were machined from the tibial diaphyses
      of 14 young, adult females ranging in age from 22 to 46 years. Data for males
      (n=17, age=17-46 years) were taken from a prior study. Measures of tissue-level
      mechanical properties, including stiffness, strength, ductility, toughness, and
      damageability, were compared between sexes using t-tests. The relationship
      between cross-sectional morphology and tissue-level mechanical properties was
      also examined. Males and females showed nearly identical tissue-level mechanical
      properties. Both sexes also showed similar age-related degradation of mechanical
      properties and a similar relationship between cross-sectional morphology and
      tissue quality. However, for all body sizes, female tibiae were smaller relative
      to body size (i.e., less robust) compared to males. The results indicated that
      sex-specific growth patterns affected transverse bone size, but did not affect
      tissue-level mechanical properties. This, combined with the observation that
      young, adult female long bones are undersized relative to body size, suggests
      that adult females would be expected to accumulate more damage under intense
      loading compared to males. This may be a contributing factor to the greater
      incidence of stress fractures observed for female military recruits.

PMID- 17035114
TI  - OP pesticides, organic diets, and children's health.

PMID- 17035117
TI  - Allergies: the new lore of spores.

PMID- 17035115
TI  - Prolactin changes as a consequence of chemical exposure.

PMID- 17035123
TI  - NTP draft brief on DEHP.

PMID- 17035124
TI  - A two-way street: building lasting community connections.

PMID- 17035126
TI  - Caring for children amidst chaos: guidelines to maintain health.

PMID- 17035127
TI  - Registering skepticism: does the EPA's pesticide review protect children?

PMID- 17035128
TI  - Embryonic insight: mouse histology in 3-D.

PMID- 17035129
TI  - Social ecology of children's vulnerability to environmental pollutants.
AB  - BACKGROUND: The outcomes of exposure to neurotoxic chemicals early in life depend
      on the properties of both the chemical and the host's environment. When our
      questions focus on the toxicant, the environmental properties tend to be regarded
      as marginal and designated as covariates or confounders. Such approaches blur the
      reality of how the early environment establishes enduring biologic substrates.
      OBJECTIVES: In this commentary, we describe another perspective, based on decades
      of biopsychological research on animals, that shows how the early, even prenatal,
      environment creates permanent changes in brain structure and chemistry and
      behavior. Aspects of the early environment-encompassing enrichment, deprivation,
      and maternal and neonatal stress-all help determine the functional responses
      later in life that derive from the biologic substrate imparted by that
      environment. Their effects then become biologically embedded. Human data,
      particularly those connected to economically disadvantaged populations, yield
      equivalent conclusions. DISCUSSION: In this commentary, we argue that treating
      such environmental conditions as confounders is equivalent to defining genetic
      differences as confounders, a tactic that laboratory research, such as that based
      on transgenic manipulations, clearly rejects. The implications extend from
      laboratory experiments that, implicitly, assume that the early environment can be
      standardized to risk assessments based on epidemiologic investigations.
      CONCLUSIONS: The biologic properties implanted by the early social environment
      should be regarded as crucial elements of the translation from laboratory
      research to human health and, in fact, should be incorporated into human health
      research. The methods for doing so are not clearly defined and present many
      challenges to investigators.

PMID- 17035130
TI  - Stable isotopic tracing-a way forward for nanotechnology.
AB  - Numerous publications and reports have expressed health and safety concerns about
      the production and use of nanoparticles, especially in areas of exposure
      monitoring, personal use, and environmental fate and transport. We suggest that
      stable isotopic tracers, which have been used widely in the earth sciences and in
      metabolic and other health-related studies for several decades, could be used to
      address many of these issues. One such example we are pursuing is the use of
      stable isotopes to monitor dermal absorption of zinc and titanium oxides in
      sunscreen preparations and other personal care products. Other potential
      applications of this tracing approach are discussed.

PMID- 17035131
TI  - Ozone's impact on public health: contributions from indoor exposures to ozone and
      products of ozone-initiated chemistry.
AB  - OBJECTIVE: The associations between ozone concentrations measured outdoors and
      both morbidity and mortality may be partially due to indoor exposures to ozone
      and ozone-initiated oxidation products. In this article I examine the
      contributions of such indoor exposures to overall ozone-related health effects by
      extensive review of the literature as well as further analyses of published data.
      FINDINGS: Daily inhalation intakes of indoor ozone (micrograms per day) are
      estimated to be between 25 and 60% of total daily ozone intake. This is
      especially noteworthy in light of recent work indicating little, if any,
      threshold for ozone's impact on mortality. Additionally, the present study
      estimates that average daily indoor intakes of ozone oxidation products are
      roughly one-third to twice the indoor inhalation intake of ozone alone. Some of
      these oxidation products are known or suspected to adversely affect human health
      (e.g., formaldehyde, acrolein, hydroperoxides, fine and ultrafine particles).
      Indirect evidence supports connections between morbidity/mortality and exposures
      to indoor ozone and its oxidation products. For example, cities with stronger
      associations between outdoor ozone and mortality tend to have residences that are
      older and less likely to have central air conditioning, which implies greater
      transport of ozone from outdoors to indoors. CONCLUSIONS: Indoor exposures to
      ozone and its oxidation products can be reduced by filtering ozone from
      ventilation air and limiting the indoor use of products and materials whose
      emissions react with ozone. Such steps might be especially valuable in schools,
      hospitals, and childcare centers in regions that routinely experience elevated
      outdoor ozone concentrations.

PMID- 17035132
TI  - Adrenocortical response to stress and thyroid hormone status in free-living
      nestling white storks (Ciconia ciconia) exposed to heavy metal and arsenic
      contamination.
AB  - BACKGROUND/OBJECTIVE: Endocrine parameters have proven useful in the detection of
      early or low-level responses to pollutants. Although most of the studies on
      endocrine modulation have been focused on processes involving gonadal steroids,
      contaminants may target other parts of the endocrine system as well. In this
      study we examined the adrenocortical stress response and thyroid hormone status
      in free-living nestling white storks (Ciconia ciconia) in relation to heavy
      metals (zinc, lead, copper, cadmium) and arsenic levels in blood. METHODS:
      Fieldwork was conducted in an area polluted by the Aznalcollar mine accident
      (southwestern Spain) and in a reference site. We used a standardized capture,
      handling, and restraint protocol to determine both baseline and maximum plasma
      corticosterone. Circulating levels of thyroxine (T4) and triiodothyronine (T3)
      were also measured. RESULTS: No effects of metals or As were found on baseline
      corticosterone, but maximum levels of corticosterone were positively related to
      Pb in both locations. This relationship was stronger in single nestlings than in
      birds from multiple-chick broods, which suggests a greater impact of Pb on more
      stressed individuals. Metal pollution did not affect plasma T4 or T3 levels,
      although thyroid status differed with location. CONCLUSIONS: Because a
      compromised hypothalamus-pituitary-adrenal (HPA) function can have far-reaching
      consequences in terms of altered behavioral and metabolic processes necessary for
      survival, our results suggest that birds exposed to sublethal Pb levels may be at
      risk through an altered adrenocortical stress response, and further support the
      idea that HPA axis-related end points might be useful indicators of metal
      exposure and potential toxicity in wild animals.

PMID- 17035133
TI  - Saxitoxin puffer fish poisoning in the United States, with the first report of
      Pyrodinium bahamense as the putative toxin source.
AB  - BACKGROUND: From January 2002 to May 2004, 28 puffer fish poisoning (PFP) cases
      in Florida, New Jersey, Virginia, and New York were linked to the Indian River
      Lagoon (IRL) in Florida. Saxitoxins (STXs) of unknown source were first
      identified in fillet remnants from a New Jersey PFP case in 2002. METHODS: We
      used the standard mouse bioassay (MBA), receptor binding assay (RBA), mouse
      neuroblastoma cytotoxicity assay (MNCA), Ridascreen ELISA, MIST Alert assay,
      HPLC, and liquid chromatography-mass spectrometry (LC-MS) to determine the
      presence of STX, decarbamoyl STX (dc-STX), and N-sulfocarbamoyl (B1) toxin in
      puffer fish tissues, clonal cultures, and natural bloom samples of Pyrodinium
      bahamense from the IRL. RESULTS: We found STXs in 516 IRL southern (Sphoeroides
      nephelus), checkered (Sphoeroides testudineus), and bandtail (Sphoeroides
      spengleri) puffer fish. During 36 months of monitoring, we detected STXs in skin,
      muscle, and viscera, with concentrations up to 22,104 microg STX equivalents
      (eq)/100 g tissue (action level, 80 microg STX eq/100 g tissue) in ovaries.
      Puffer fish tissues, clonal cultures, and natural bloom samples of P. bahamense
      from the IRL tested toxic in the MBA, RBA, MNCA, Ridascreen ELISA, and MIST Alert
      assay and positive for STX, dc-STX, and B1 toxin by HPLC and LC-MS. Skin mucus of
      IRL southern puffer fish captive for 1-year was highly toxic compared to Florida
      Gulf coast puffer fish. Therefore, we confirm puffer fish to be a hazardous
      reservoir of STXs in Florida's marine waters and implicate the dinoflagellate P.
      bahamense as the putative toxin source. CONCLUSIONS: Associated with fatal
      paralytic shellfish poisoning (PSP) in the Pacific but not known to be toxic in
      the western Atlantic, P. bahamense is an emerging public health threat. We
      propose characterizing this food poisoning syndrome as saxitoxin puffer fish
      poisoning (SPFP) to distinguish it from PFP, which is traditionally associated
      with tetrodotoxin, and from PSP caused by STXs in shellfish.

PMID- 17035134
TI  - Mortality and exposure response among 14,458 electrical capacitor manufacturing
      workers exposed to polychlorinated biphenyls (PCBs).
AB  - BACKGROUND: We expanded an existing cohort of workers (n = 2,588) considered
      highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing
      plants to include all workers with at least 90 days of potential PCB exposure
      during 1939-1977 (n = 14,458). Causes of death of a priori interest included
      liver and rectal cancers, previously reported for the original cohort, and non
      Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and
      prostate cancers, based on other studies. METHODS: We ascertained vital status of
      the workers through 1998, and cumulative PCB exposure was estimated using a new
      job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S.,
      state, and county referents) and Poisson regression modeling. RESULTS: Mortality
      from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess
      nor associated with cumulative exposure. Mortality was not elevated for liver
      cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55-1.36], but
      increased with cumulative exposure (trend p-value = 0.071). Among men, stomach
      cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98-2.28) and
      increased with cumulative exposure (trend p-value = 0.039). Among women,
      intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02
      1.66), especially in higher cumulative exposure categories, but without a clear
      trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04;
      95% CI, 0.72-1.45), increased with cumulative exposure (trend p-value = 0.0001).
      CONCLUSIONS: This study corroborates previous studies showing increased liver
      cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal
      cancers with PCB exposure. This is the first PCB cohort showing a strong exposure
      response relationship for prostate cancer mortality.

PMID- 17035135
TI  - Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey
      of U.S. food and estimated PBDE dietary intake by age and sex.
AB  - OBJECTIVES: Our objectives in this study were to expand a previously reported
      U.S. market basket survey using a larger sample size and to estimate levels of
      PBDE intake from food for the U.S. general population by sex and age. METHODS: We
      measured concentrations of 13 polybrominated diphenyl ether (PBDE) congeners in
      food in 62 food samples. In addition, we estimated levels of PBDE intake from
      food for the U.S. general population by age (birth through > or = 60 years of
      age) and sex. RESULTS: In food samples, concentrations of total PBDEs varied from
      7.9 pg/g (parts per trillion) in milk to 3,726 pg/g in canned sardines. Fish were
      highest in PBDEs (mean, 1,120 pg/g; median, 616 pg/g; range, 11.14-3,726 pg/g).
      This was followed by meat (mean, 383 pg/g; median, 190 pg/g; range, 39-1,426
      pg/g) and dairy products (mean, 116 pg/g; median, 32.2 pg/g; range, 7.9-683
      pg/g). However, using estimates for food consumption (excluding nursing infants),
      meat accounted for the highest U.S. dietary PBDE intake, followed by dairy and
      fish, with almost equal contributions. Adult females had lower dietary intake of
      PBDEs than did adult males, based on body weight. We estimated PBDE intake from
      food to be 307 ng/kg/day for nursing infants and from 2 ng/kg/day at 2-5 years of
      age for both males and females to 0.9 ng/kg/day in adult females. CONCLUSION:
      Dietary exposure alone does not appear to account for the very high body burdens
      measured. The indoor environment (dust, air) may play an important role in PBDE
      body burdens in addition to food.

PMID- 17035136
TI  - Cancer incidence among pesticide applicators exposed to dicamba in the
      agricultural health study.
AB  - BACKGROUND: Dicamba is an herbicide commonly applied to crops in the United
      States and abroad. We evaluated cancer incidence among pesticide applicators
      exposed to dicamba in the Agricultural Health Study, a prospective cohort of
      licensed pesticide applicators in North Carolina and Iowa. METHODS: Detailed
      pesticide exposure information was obtained through a self-administered
      questionnaire completed from 1993 to 1997. Cancer incidence was followed through
      31 December 2002 by linkage to state cancer registries. We used Poisson
      regression to estimate rate ratios and 95% confidence intervals for cancer
      subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used:
      lifetime exposure days and intensity-weighted lifetime exposure days (lifetime
      days x intensity score). RESULTS: A total of 41,969 applicators were included in
      the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not
      associated with overall cancer incidence nor were there strong associations with
      any specific type of cancer. When the reference group comprised low-exposed
      applicators, we observed a positive trend in risk between lifetime exposure days
      and lung cancer (p = 0.02), but none of the individual point estimates was
      significantly elevated. We also observed significant trends of increasing risk
      for colon cancer for both lifetime exposure days and intensity-weighted lifetime
      days, although these results are largely due to elevated risk at the highest
      exposure level. There was no apparent risk for non-Hodgkin lymphoma. CONCLUSIONS:
      Although associations between exposure and lung and colon cancer were observed,
      we did not find clear evidence for an association between dicamba exposure and
      cancer risk.

PMID- 17035137
TI  - Nitrate intake does not influence bladder cancer risk: the Netherlands cohort
      study.
AB  - OBJECTIVES: N-nitroso compounds, endogenously formed from nitrate-derived
      nitrite, are suspected to be important bladder carcinogens. However, the
      association between nitrate exposure from food or drinking water and bladder
      cancer has not been substantially investigated in epidemiologic studies. METHODS:
      We evaluated the associations between nitrate exposure and bladder cancer in the
      Netherlands Cohort Study, conducted among 120,852 men and women, 55-69 years of
      age at entry. Information on nitrate from diet was collected via a food frequency
      questionnaire in 1986 and a database on nitrate content of foods. Individual
      nitrate exposures from beverages prepared with tap water were calculated by
      linking the postal code of individual residence at baseline to water company
      data. After 9.3 years of follow-up and after excluding subjects with incomplete
      or inconsistent dietary data, 889 cases and 4,441 subcohort members were
      available for multivariate analyses. We calculated incidence rate ratios (RR) and
      corresponding 95% confidence intervals (CIs) using Cox regression analyses. We
      also evaluated possible effect modification of dietary intake of vitamins C and E
      (low/high) and cigarette smoking (never/ever). RESULTS: The multivariate RRs for
      nitrate exposure from food, drinking water, and estimated total nitrate exposure
      were 1.06 (95% CI, 0.81-1.31), 1.06 (95% CI, 0.82-1.37), and 1.09 (95% CI, 0.84
      1.42), respectively, comparing the highest to the lowest quintiles of intake.
      Dietary intake of vitamins C and E (low/high) and cigarette smoking (never/ever)
      had no significant impact on these results. CONCLUSION: Although the association
      between nitrate exposure and bladder cancer risk is biologically plausible, our
      results in this study do not support an association between nitrate exposure and
      bladder cancer risk.

PMID- 17035138
TI  - Public health impact of extremely low-frequency electromagnetic fields.
AB  - INTRODUCTION: The association between exposure to extremely low-frequency
      electric and magnetic fields (ELF) and childhood leukemia has led to the
      classification of magnetic fields by the International Agency for Research on
      Cancer as a "possible human carcinogen." This association is regarded as the
      critical effect in risk assessment. Creating effective policy in light of
      widespread exposure and the undisputed value of safe, reliable, and economic
      electricity to society is difficult and requires estimates of the potential
      public health impact and associated uncertainties. OBJECTIVES: Although a causal
      relationship between magnetic fields and childhood leukemia has not been
      established, we present estimates of the possible pubic health impact using
      attributable fractions to provide a potentially useful input into policy analysis
      under different scenarios. METHODS: Using ELF exposure distributions from various
      countries and dose-response functions from two pooled analyses, we calculate
      country-specific and worldwide estimates of attributable fractions (AFs) and
      attributable cases. RESULTS: Even given a wide range of assumptions, we find that
      the AF remains < 10%, with point estimates ranging from < 1% to about 4%. For
      small countries with low exposure, the number of attributable cases is less than
      one extra case per year. Worldwide the range is from 100 to 2,400 cases possibly
      attributable to ELF exposure. CONCLUSION: The fraction of childhood leukemia
      cases possibly attributable to ELF exposure across the globe appears to be small.
      There remain, however, a number of uncertainties in these AF estimates,
      particularly in the exposure distributions.

PMID- 17035139
TI  - Blood lead levels and death from all causes, cardiovascular disease, and cancer:
      results from the NHANES III mortality study.
AB  - BACKGROUND: Analyses of mortality data for participants examined in 1976-1980 in
      the second National Health and Nutrition Examination Survey (NHANES II) suggested
      an increased risk of mortality at blood lead levels > 20 microg/dL. Blood lead
      levels have decreased markedly since the late 1970s. In NHANES III, conducted
      during 1988-1994, few adults had levels > 20 microg/dL. OBJECTIVE: Our objective
      in this study was to determine the risk of mortality in relation to lower blood
      lead levels observed for adult participants of NHANES III. METHODS: We analyzed
      mortality information for 9,757 participants who had a blood lead measurement and
      who were > or = 40 years of age at the baseline examination. Using blood lead
      levels categorized as < 5, 5 to < 10, and > or = 10 microg/dL, we determined the
      relative risk of mortality from all causes, cancer, and cardiovascular disease
      through Cox proportional hazard regression analysis. RESULTS: Using blood lead
      levels < 5 microg/dL as the referent, we determined that the relative risk of
      mortality from all causes was 1.24 [95% confidence interval (CI), 1.05-1.48] for
      those with blood levels of 5-9 microg/dL and 1.59 (95% CI, 1.28-1.98) for those
      with blood levels > or = 10 microg/dL (p for trend < 0.001). The magnitude of
      risk was similar for deaths due to cardiovascular disease and cancer, and tests
      for trend were statistically significant (p < 0.01) for both causes of death.
      CONCLUSION: In a nationally representative sample of the U.S. population, blood
      lead levels as low as 5-9 mug/dL were associated with an increased risk of death
      from all causes, cardiovascular disease, and cancer.

PMID- 17035140
TI  - Organophosphate insecticides target the serotonergic system in developing rat
      brain regions: disparate effects of diazinon and parathion at doses spanning the
      threshold for cholinesterase inhibition.
AB  - BACKGROUND: In the developing brain, serotonin (5HT) systems are among the most
      sensitive to disruption by organophosphates. OBJECTIVES: We exposed neonatal rats
      to daily doses of diazinon or parathion on postnatal days (PND)1-4 and evaluated
      5HT receptors and the 5HT transporter in brainstem and forebrain on PND5,
      focusing on doses of each agent below the maximum tolerated dose and spanning the
      threshold for cholinesterase inhibition: 0.5, 1, or 2 mg/kg for diazinon, and
      0.02, 0.05, and 0.1 mg/kg for parathion. RESULTS: Diazinon evoked up-regulation
      of 5HT1A and 5HT2 receptor expression even at doses devoid of effects on
      cholinesterase activity, a pattern similar to that seen earlier for another
      organophosphate, chlorpyrifos. In contrast, parathion decreased 5HT1A receptors,
      again at doses below those required for effects on cholinesterase. The two agents
      also differed in their effects on the 5HT transporter. Diazinon evoked a decrease
      in the brainstem and an increase in the forebrain, again similar to that seen for
      chlorpyrifos; this pattern is typical of damage of nerve terminals and reactive
      sprouting. Parathion had smaller, nonsignificant effects. CONCLUSIONS: Our
      results buttress the idea that, in the developing brain, the various
      organophosphates target specific neurotransmitter systems differently from each
      other and without the requirement for cholinesterase inhibition, their supposed
      common mechanism of action.

PMID- 17035142
TI  - Persistence of symptoms in veterans of the First Gulf War: 5-year follow-up.
AB  - BACKGROUND: During the 1990-1991 Gulf War, approximately 700,000 U.S. troops were
      deployed to the Persian Gulf theater of operations. Of that number, approximately
      100,000 have presented medical complaints through various registry and
      examination programs. OBJECTIVES: Widespread symptomatic illness without defining
      physical features has been reported among veterans of the 1991 Gulf War. We
      ascertained changes in symptom status between an initial 1995 symptom evaluation
      and a follow-up in 2000. METHODS: We assessed mailed symptom survey
      questionnaires for 390 previously surveyed members of the U.S. Department of
      Veterans Affairs Gulf War Registry for changes over the 5-year interval in terms
      of number and severity of symptoms. RESULTS: For the cohort as a whole, we found
      no significant changes in symptom number or severity. Those initially more
      symptomatic in 1995 showed some improvement over time, but remained much more
      highly symptomatic than those who had lesser initial symptomatology. CONCLUSIONS:
      The symptom outbreak following the 1991 Gulf War has not abated over time in
      registry veterans, suggesting substantial need for better understanding and care
      for these veterans.

PMID- 17035141
TI  - Neural tube defects and folate pathway genes: family-based association tests of
      gene-gene and gene-environment interactions.
AB  - BACKGROUND: Folate metabolism pathway genes have been examined for association
      with neural tube defects (NTDs) because folic acid supplementation reduces the
      risk of this debilitating birth defect. Most studies addressed these genes
      individually, often with different populations providing conflicting results.
      OBJECTIVES: Our study evaluates several folate pathway genes for association with
      human NTDs, incorporating an environmental cofactor: maternal folate
      supplementation. METHODS: In 304 Caucasian American NTD families with
      myelomeningocele or anencephaly, we examined 28 polymorphisms in 11 genes: folate
      receptor 1, folate receptor 2, solute carrier family 19 member 1, transcobalamin
      II, methylenetetrahydrofolate dehydrogenase 1, serine hydroxymethyl-transferase
      1, 5,10-methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate
      homo-cysteine methyltransferase, 5-methyltetrahydrofolate-homocysteine
      methyltransferase reductase, betaine-homocysteine methyltransferase (BHMT), and
      cystathionine-beta-synthase. RESULTS: Only single nucleotide polymorphisms (SNPs)
      in BHMT were significantly associated in the overall data set; this significance
      was strongest when mothers took folate-containing nutritional supplements before
      conception. The BHMT SNP rs3733890 was more significant when the data were
      stratified by preferential transmission of the MTHFR rs1801133 thermolabile T
      allele from parent to offspring. Other SNPs in folate pathway genes were
      marginally significant in some analyses when stratified by maternal
      supplementation, MTHFR, or BHMT allele transmission. CONCLUSIONS: BHMT rs3733890
      is significantly associated in our data set, whereas MTHFR rs1801133 is not a
      major risk factor. Further investigation of folate and methionine cycle genes
      will require extensive SNP genotyping and/or resequencing to identify novel
      variants, inclusion of environmental factors, and investigation of gene-gene
      interactions in large data sets.

PMID- 17035143
TI  - A cancer risk assessment of inner-city teenagers living in New York City and Los
      Angeles.
AB  - BACKGROUND: The Toxics Exposure Assessment Columbia-Harvard (TEACH) project
      assessed exposures and cancer risks from urban air pollutants in a population of
      high school teenagers in New York City (NYC) and Los Angeles (LA). Forty-six high
      school students participated in NYC and 41 in LA, most in two seasons in 1999 and
      2000, respectively. METHODS: Personal, indoor home, and outdoor home 48-hr
      samples of volatile organic compounds (VOCs), aldehydes, particulate matter with
      aerodynamic diameter < or = 2.5 microm, and particle-bound elements were
      collected. Individual cancer risks for 13 VOCs and 6 particle-bound elements were
      calculated from personal concentrations and published cancer unit risks. RESULTS:
      The median cumulative risk from personal VOC exposures for this sample of NYC
      high school students was 666 per million and was greater than the risks from
      ambient exposures by a factor of about 5. In the LA sample, median cancer risks
      from VOC personal exposures were 486 per million, about a factor of 4 greater
      than ambient exposure risks. The VOCs with the highest cancer risk included 1,4
      dichlorobenzene, formaldehyde, chloroform, acetaldehyde, and benzene. Of these,
      benzene had the greatest contributions from outdoor sources. All others had high
      contributions from indoor sources. The cumulative risks from personal exposures
      to the elements were an order of magnitude lower than cancer risks from VOC
      exposures. CONCLUSIONS: Most VOCs had median upper-bound lifetime cancer risks
      that exceeded the U.S. Environmental Protection Agency (EPA) benchmark of 1 x 10
      6 and were generally greater than U.S. EPA modeled estimates, more so for
      compounds with predominant indoor sources. Chromium, nickel, and arsenic had
      median personal cancer risks above the U.S. EPA benchmark with exposures largely
      from outdoors and other microenvironments. The U.S. EPA-modeled concentrations
      tended to overestimate personal cancer risks for beryllium and chromium but
      underestimate risks for nickel and arsenic.

PMID- 17035144
TI  - Chlorinated pool attendance, atopy, and the risk of asthma during childhood.
AB  - The pool chlorine hypothesis postulates that the rise in childhood asthma in the
      developed world could result at least partly from the increasing exposure of
      children to toxic gases and aerosols contaminating the air of indoor chlorinated
      pools. To further assess this hypothesis, we explored the relationships between
      childhood asthma, atopy, and cumulated pool attendance (CPA). We studied 341
      schoolchildren 10-13 years of age who attended at a variable rate the same public
      pool in Brussels (trichloramine in air, 0.3-0.5 mg/m3). Examination of the
      children included a questionnaire, an exercise-induced bronchoconstriction (EIB)
      test, and the measurement of exhaled nitric oxide (eNO) and total and
      aeroallergen-specific serum IgE. CPA by children (range, 0-1,818 hr) emerged
      among the most consistent predictors of asthma (doctor diagnosed or screened with
      the EIB test) and of elevated eNO, ranking immediately after atopy and family
      history of asthma or hay fever. Although the risk of elevated eNO increased with
      CPA [odds ratio (OR) = 1.30; 95% confidence interval (CI), 1.10-1.43]
      independently of total or specific serum IgE, the probability of developing
      asthma increased with CPA only in children with serum IgE > 100 kIU/L (OR for
      each 100-hr increase in CPA = 1.79; 95% CI, 1.07-2.72). All these effects were
      dose related and most strongly linked to pool attendance before 6-7 years of age.
      Use of indoor chlorinated pools especially by young children interacts with
      atopic status to promote the development of childhood asthma. These findings
      further support the hypothesis implicating pool chlorine in the rise of childhood
      asthma in industrialized countries.

PMID- 17035145
TI  - Reduction in asthma morbidity in children as a result of home remediation aimed
      at moisture sources.
AB  - OBJECTIVE: Home dampness and the presence of mold and allergens have been
      associated with asthma morbidity. We examined changes in asthma morbidity in
      children as a result of home remediation aimed at moisture sources. DESIGN: In
      this prospective, randomized controlled trial, symptomatic, asthmatic children (n
      = 62), 2-17 years of age, living in a home with indoor mold, received an asthma
      intervention including an action plan, education, and individualized problem
      solving. The remediation group also received household repairs, including
      reduction of water infiltration, removal of water-damaged building materials, and
      heating/ventilation/air-conditioning alterations. The control group received only
      home cleaning information. We measured children's total and allergen-specific
      serum immuno-globulin E, peripheral blood eosinophil counts, and urinary
      cotinine. Environmental dust samples were analyzed for dust mite, cockroach,
      rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year.
      RESULTS: Children in both groups showed improvement in asthma symptomatic days
      during the preremediation portion of the study. The remediation group had a
      significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent
      to treat) after remodeling, whereas these parameters in the control group did not
      significantly change. In the postremediation period, the remediation group had a
      lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29
      vs. 11 of 33, respectively, p = 0. 003; intent to treat: 28.1% and 10.0%,
      respectively, p = 0.11). CONCLUSION: Construction remediation aimed at the root
      cause of moisture sources and combined with a medical/behavioral intervention
      significantly reduces symptom days and health care use for asthmatic children who
      live in homes with a documented mold problem.

PMID- 17035146
TI  - Children show highest levels of polybrominated diphenyl ethers in a California
      family of four: a case study.
AB  - Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants, are
      ubiquitous environmental contaminants with particularly high concentrations in
      humans from the United States. This study is a first attempt to report and
      compare PBDE concentrations in blood drawn from a family. Serum samples from
      family members collected at two sampling occasions 90 days apart were analyzed
      for PBDE congeners. Concentrations of the lower-brominated PBDEs were similar at
      the two sampling times for each family member, with children's levels 2- to 5
      fold higher than those of their parents. Concentrations of, for example,
      2,2',4,4'-tetrabromodiphenyl ether (BDE-47) varied from 32 ng/g lipid weight (lw)
      in the father to 60, 137, and 245 ng/g lw in the mother, child, and toddler,
      respectively. Decabromodiphenyl ether (BDE-209) concentrations differed
      significantly between the two samplings. September concentrations in the father,
      mother, child, and toddler were 23, 14, 143, and 233 ng/g lw, respectively.
      December concentrations (duplicate results from the laboratory) were 2 and 3, 4
      and 4, 9 and 12, and 19 and 26 ng/g lw, respectively. Parents' summation
      operatorPBDE concentrations approached U.S. median concentrations, with
      children's concentrations near the maximum (top 5%) found in U.S. adults. The
      youngest child had the highest concentrations of all PBDE congeners, suggesting
      that younger children are more exposed to PBDEs than are adults. Our estimates
      indicate that house dust contributes to children's higher PBDE levels. BDE-209
      levels for all family members were 10-fold lower at the second sampling. The
      short half-life of BDE-209 (15 days) indicates that BDE-209 levels can decrease
      rapidly in response to decreased exposures. This case study suggests that
      children are at higher risk for PBDE exposures and, accordingly, face higher
      risks of PBDE-related health effects than adults.

PMID- 17035147
TI  - The economic impact of early life environmental tobacco smoke exposure: early
      intervention for developmental delay.
AB  - BACKGROUND AND OBJECTIVES: Early-life exposure to environmental tobacco smoke
      (ETS) can result in developmental delay as well as childhood asthma and increased
      risk of cancer. The high cost of childhood asthma related to ETS exposure has
      been widely recognized; however, the economic impact of ETS-related developmental
      delay has been less well understood. METHODS AND RESULTS: The Columbia Center for
      Children's Environmental Health (CCCEH) has reported adverse effects of prenatal
      ETS exposure on child development in a cohort of minority women and children in
      New York City (odds ratio of developmental delay = 2.36; 95% confidence interval
      1.22-4.58). Using the environmentally attributable fraction (EAF) approach, we
      estimated the annual cost of one aspect of ETS-related developmental delay: Early
      Intervention Services. The estimated cost of these services per year due to ETS
      exposure is > Dollars 50 million per year for New York City Medicaid births and
      Dollars 99 million per year for all New York City births. CONCLUSION: The high
      annual cost of just one aspect of developmental delay due to prenatal exposure to
      ETS provides further impetus for increased prevention efforts such as educational
      programs to promote smoke-free homes, additional cigarette taxes, and subsidizing
      of smoking cessation programs.

PMID- 17035148
TI  - Agricultural pesticide use and hypospadias in eastern Arkansas.
AB  - INTRODUCTION: We assessed the relationship between hypospadias and proximity to
      agricultural pesticide applications using a GIS-based exposure method. METHODS:
      We obtained information for 354 cases of hypospadias born between 1998 and 2002
      in eastern Arkansas; 727 controls were selected from birth certificates. We
      classified exposure on pounds of pesticides (estimated by crop type) applied or
      persisting within 500 m of each subject's home during gestational weeks 6 to 16.
      We restricted our analyses to 38 pesticides with some evidence of reproductive,
      developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of
      pesticide applications using crop phenology and published records. RESULTS:
      Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI),
      0.83-0.99], parity (OR = 0.79; 95% CI, 0.65-0.95), and delaying prenatal care
      until the third trimester (OR = 4.04; 95% CI, 1.46-11.23) were significantly
      associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05
      pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI,
      1.01-1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70-0.96)
      and applications of alachlor (OR = 0.56; 95% CI, 0.35-0.89) and permethrin (OR =
      0.37; 95% CI, 0.16-0.86) were negatively associated with hypospadias.
      CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated
      exposure to pesticides known to have reproductive, developmental, or endocrine
      disrupting effects increases risk of hypospadias. Further research on the
      potential effects of exposure to diclofop-methyl is recommended.

PMID- 17035149
TI  - Age- and concentration-dependent elimination half-life of 2,3,7,8
      tetrachlorodibenzo-p-dioxin in Seveso children.
AB  - OBJECTIVE: Pharmacokinetic and statistical analyses are reported to elucidate key
      variables affecting 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in
      children and adolescents. DESIGN: We used blood concentrations to calculate TCDD
      elimination half-life. Variables examined by statistical analysis include age,
      latency from exposure, sex, TCDD concentration and quantity in the body, severity
      of chloracne response, body mass index, and body fat mass. PARTICIPANTS: Blood
      was collected from 1976 to 1993 from residents of Seveso, Italy, who were < 18
      years of age at the time of a nearby trichlorophenol reactor explosion in July
      1976. RESULTS: TCDD half-life in persons < 18 years of age averaged 1.6 years
      while those > or =18 years of age averaged 3.2 years. Half-life is strongly
      associated with age, showing a cohort average increase of 0.12 year half-life per
      year of age or time since exposure. A significant concentration-dependency is
      also identified, showing shorter half-lives for TCDD concentrations > 400 ppt for
      children < 12 years of age and 700 ppt when including adults. Moderate
      correlations are also observed between half-life and body mass index, body fat
      mass, TCDD mass, and chloracne response. CONCLUSIONS: Children and adolescents
      have shorter TCDD half-lives and a slower rate of increase in half-life than
      adults, and this effect is augmented at higher body burdens. RELEVANCE: Modeling
      of TCDD blood concentrations or body burden in humans should take into account
      the markedly shorter elimination half-life observed in children and adolescents
      and concentration-dependent effects observed in persons > 400-700 ppt.

PMID- 17035150
TI  - An exploration of ethical issues in research in children's health and the
      environment.
AB  - The consideration of ethical issues relating to pediatric environmental health is
      a recent phenomenon. Discussions of biomedical ethics, research on children, and
      environmental health research have a longer history. In the late 1990s,
      researchers at the Kennedy Krieger Institute in Baltimore, Maryland, undertook a
      study to compare the effectiveness of several methods of reducing lead risk in
      housing. In a preliminary finding in the case of Grimes v. Kennedy Krieger
      Institute, Inc., a Maryland court questioned the ethics of performing research on
      children when there is no prospect of direct benefit to those children and
      whether parents can consent to such research. This case dramatically raised the
      profile of ethical issues among the pediatric environmental health research
      community. To broaden the discussion of these issues and in response to the
      Kennedy-Krieger case, the Children's Environmental Health Network held a working
      meeting on 5 and 6 March 2004 to explore this topic. The articles in this mini
      monograph were prepared by the authors as a result of the workshop and represent
      their opinions. This article is an introduction to the workshop and a summary of
      the articles to follow.

PMID- 17035151
TI  - Trials and tribulations of protecting children from environmental hazards.
AB  - Society is increasingly aware of the profound impact that the environment has on
      children's health. Not surprisingly, there is increasing public scrutiny about
      children's exposures to environmental hazards, especially for disadvantaged
      children. These trends underscore the ethical imperative to develop a framework
      to protect children from environmental hazards. Such a framework must include
      regulations to test new chemicals and other potential hazards before they are
      marketed, a strategy to conduct research necessary to protect children from
      persistent hazards that are widely dispersed in their environment, stronger
      regulatory mechanisms to eliminate human exposures to recognized or suspected
      toxicants, and guidelines about the ethical conduct of research and the role of
      experimental trials that test the efficacy and safety of interventions to prevent
      or ameliorate children's exposure to persistent toxicants or hazards that are
      widely dispersed in their environment.

PMID- 17035152
TI  - The politics of risk: a human rights paradigm for children's environmental health
      research.
AB  - A human rights paradigm for environmental health research makes explicit the
      relationship between poor health and poverty, inequality, and social and
      political marginalization, and it aims at civic problem solving. In so doing, it
      incorporates support for community-based, participatory research and takes
      seriously the social responsibilities of researchers. For these reasons, a human
      rights approach may be better able than conventional bioethics to address the
      unique issues that arise in the context of pediatric environmental health
      research, particularly the place of environmental justice standards in research.
      At the same time, as illustrated by disagreements over the ethics of research
      into lead abatement methods, bringing a human rights paradigm to bear in the
      context of environmental health research requires resolving important tensions at
      its heart, particularly the inescapable tension between ethical ideals and
      political realities.

PMID- 17035153
TI  - Privacy and ethics in pediatric environmental health research-part I: genetic and
      prenatal testing.
AB  - The pressing need for empirically informed public policies aimed at understanding
      and promoting children's health has challenged environmental scientists to modify
      traditional research paradigms and reevaluate their roles and obligations toward
      research participants. Methodologic approaches to children's environmental health
      research raise ethical challenges for which federal regulations may provide
      insufficient guidance. In this article I begin with a general discussion of
      privacy concerns and informed consent within pediatric environmental health
      research contexts. I then turn to specific ethical challenges associated with
      research on genetic determinants of environmental risk, prenatal studies and
      maternal privacy, and data causing inflicted insight or affecting the
      informational rights of third parties.

PMID- 17035154
TI  - Privacy and ethics in pediatric environmental health research-part II: protecting
      families and communities.
AB  - BACKGROUND: In pediatric environmental health research, information about family
      members is often directly sought or indirectly obtained in the process of
      identifying child risk factors and helping to tease apart and identify
      interactions between genetic and environmental factors. However, federal
      regulations governing human subjects research do not directly address ethical
      issues associated with protections for family members who are not identified as
      the primary "research participant." Ethical concerns related to family consent
      and privacy become paramount as pediatric environmental health research
      increasingly turns to questions of gene-environment interactions. OBJECTIVES: In
      this article I identify issues arising from and potential solutions for the
      privacy and informed consent challenges of pediatric environmental health
      research intended to adequately protect the rights and welfare of children,
      family members, and communities. DISCUSSION: I first discuss family members as
      secondary research participants and then the specific ethical challenges of
      longitudinal research on late-onset environmental effects and gene-environment
      interactions. I conclude with a discussion of the confidentiality and social
      risks of recruitment and data collection of research conducted within small or
      unique communities, ethnic minority populations, and low-income families.
      CONCLUSIONS: The responsible conduct of pediatric environmental health research
      must be conceptualized as a goodness of fit between the specific research context
      and the unique characteristics of subjects and other family stakeholders.

PMID- 17035155
TI  - Supplementing the traditional institutional review board with an environmental
      health and community review board.
AB  - BACKGROUND: Community-based research often involves additional ethical, legal,
      and social considerations beyond those of the specific individuals involved in
      the study. The traditional institutional review board (IRB) typically focuses on
      protecting the rights and ensuring the safety of the individuals involved. For
      projects involving community members, IRBs should be more sensitive to issues
      related to the broader community concerns. OBJECTIVES: The objective of this
      article is to discuss the concept of community-based participatory research and
      the shortcomings of the traditional IRBs in dealing with ethical issues
      associated with broader community concerns such as implications for family
      members, neighborhood groups, and local businesses. I examine the rationale and
      benefits for expanding the roles and responsibilities of review boards related to
      community-based issues. DISCUSSION: I propose the development of environmental
      health and community review boards (EHCRBs) that combine the fundamental
      responsibilities and ethical concept of the traditional review boards with an
      expanded ethical construct of dignity, veracity, sustainability, and justice,
      with an added emphasis on community. CONCLUSIONS: Only by acknowledging the needs
      of and working with the community can we ensure ethically based and socially
      responsible research. An EHCRB will allow researchers and community members to
      more fully address their mutual interest in conducting scientific, ethical, and
      socially responsible research.

PMID- 17035162
TI  - Vitiligo treatment options: an evolving scenario.
AB  - Sequential displays of several treatment options for vitiligo have been scanned
      from the literature, and are presented here. A few of the medical modalities have
      been resigned to history, whereas others have become customary in clinical
      practice. There has also been a recent surge of interest in the surgical
      treatment of this disease. Accordingly, this has been appraised and summarized.
      Special attention has been given to prevalent medical modalities so that they may
      be effectively utilized by those currently in practice.

PMID- 17035163
TI  - Psychosocial stress impairs working memory at high loads: an association with
      cortisol levels and memory retrieval.
AB  - Stress and cortisol are known to impair memory retrieval of well-consolidated
      declarative material. The effects of cortisol on memory retrieval may in
      particular be due to glucocorticoid (GC) receptors in the hippocampus and
      prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be
      observable on both hippocampal-dependent declarative memory retrieval and PFC
      dependent working memory (WM). In the present study, it was tested whether
      psychosocial stress would impair both WM and memory retrieval in 20 young healthy
      men. In addition, the association between cortisol levels and cognitive
      performance was assessed. It was found that stress impaired WM at high loads, but
      not at low loads in a Sternberg paradigm. High cortisol levels at the time of
      testing were associated with slow WM performance at high loads, and with impaired
      recall of moderately emotional, but not of highly emotional paragraphs.
      Furthermore, performance at high WM loads was associated with memory retrieval.
      These data extend previous results of pharmacological studies in finding WM
      impairments after acute stress at high workloads and cortisol-related retrieval
      impairments.

PMID- 17035164
TI  - Comparison of intramuscular and intradermal applications of hepatitis B vaccine
      in hemodialysis patients.
AB  - This study compared the application of intramuscular recombinant hepatitis B
      vaccine in hemodialysis patients with the application of accelerated intradermal
      recombinant hepatitis B vaccine, which can be applied with one-tenth of the
      standard dose. Sixty seronegative patients for hepatitis B were randomly
      separated into two groups. Twenty mug of the recombinant hepatitis B vaccine was
      intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group
      (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers
      remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied
      at 2 microg dose six times with one-month intervals to the second group (28
      cases). Vaccine applications were continued in those whose anti-HBs titers
      remained below 100 mIU/mL at month 7 until antibody titers reached above this
      value or until the dose number became 12. Measurements of antibody titers were
      repeated at month 13 in both groups. As a result, in the vaccination of
      hemodialysis patients against hepatitis B, the accelerated ID application of
      hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than
      the standard dose vaccination schedules. Especially for hemodialysis patients,
      the time has come for routine application of ID hepatitis B vaccine as an
      alternative vaccination method.

PMID- 17035165
TI  - The effects of caffeine ingestion on performance time, speed and power during a
      laboratory-based 1 km cycling time-trial.
AB  - There is little published data in relation to the effects of caffeine upon
      cycling performance, speed and power in trained cyclists, especially during
      cycling of approximately 60 s duration. To address this, eight trained cyclists
      performed a 1 km time-trial on an electronically braked cycle ergometer under
      three conditions: after ingestion of 5 mg x kg-1 caffeine, after ingestion of a
      placebo, or a control condition. The three time-trials were performed in a
      randomized order and performance time, mean speed, mean power and peak power were
      determined. Caffeine ingestion resulted in improved performance time (caffeine
      vs. placebo vs. control: 71.1 +/- 2.0 vs. 73.4 +/- 2.3 vs. 73.3 +/- 2.7 s; P =
      0.02; mean +/- s). This change represented a 3.1% (95% confidence interval: 0.7
      5.6) improvement compared with the placebo condition. Mean speed was also higher
      in the caffeine than placebo and control conditions (caffeine vs. placebo vs.
      control: 50.7 +/- 1.4 vs. 49.1 +/- 1.5 vs. 49.2 +/- 1.7 km x h-1; P = 0.0005).
      Mean power increased after caffeine ingestion (caffeine vs. placebo vs. control:
      523 +/- 43 vs. 505 +/- 46 vs. 504 +/- 38 W; P = 0.007). Peak power also increased
      from 864 +/- 107 W (placebo) and 830 +/- 87 W (control) to 940 +/- 83 W after
      caffeine ingestion (P = 0.027). These results provide support for previous
      research that found improved performance after caffeine ingestion during short
      duration high-intensity exercise. The magnitude of the improvements observed in
      our study could be due to our use of sport-specific ergometry, a tablet form and
      trained participants.

PMID- 17035166
TI  - Sex differences in the onset of seasonal reproductive quiescence in hamsters.
AB  - Day length is the primary cue used by many mammals to restrict reproduction to
      favourable spring and summer months, but it is unknown for any mammal whether the
      seasonal loss of fertility begins at the same time and occurs at the same rate in
      females and males; nor it established whether the termination of mating behaviour
      in males and females coincides with the loss of fertility. We speculated that
      females, owing to their greater energetic investment in reproduction, are the
      limiting sex in terminating offspring production in short days (SDs). Oestrous
      cycles and production of young were monitored in Syrian hamsters (Mesocricetus
      auratus) transferred from long days (LDs) to SDs. Females were mated to LD males
      after three to eight weeks of SD treatment; in a parallel experiment, males
      housed in SDs were mated to LD females. After five and eight weeks in SDs, at
      least twice as many males as females were fertile. Both males and females
      continued to copulate for several weeks after becoming infertile. The onset of
      seasonal infertility occurs earlier in females than males and the decline in
      fertility precedes the seasonal loss of mating behaviour in both sexes.

PMID- 17035167
TI  - Mating trials validate the use of DNA barcoding to reveal cryptic speciation of a
      marine bryozoan taxon.
AB  - Despite increasing threats to the marine environment, only a fraction of the
      biodiversity of the oceans has been described, owing in part to the widespread
      occurrence of cryptic species. DNA-based barcoding through screening of an
      orthologous reference gene has been proposed as a powerful tool to uncover
      biological diversity in the face of dwindling taxonomic expertise and the
      limitations of traditional species identification. Although DNA barcoding should
      be particularly useful in the sea, given the prevalence of marine cryptic
      species, the link between taxa identified through DNA barcodes and reproductively
      isolated taxa (biological species) has rarely been explicitly tested. Here, we
      use an integrated framework comparing breeding compatibility, morphology and
      mitochondrial (cytochrome c oxidase 1) and nuclear (elongation factor-1-alpha)
      DNA sequence variation among globally distributed samples of the cosmopolitan
      marine bryozoan Celleporella hyalina (L.). Our results reveal that C. hyalina
      comprises numerous deep, mostly allopatric, genetic lineages that are
      reproductively isolated, yet share very similar morphology, indicating rampant
      cryptic speciation. The close correspondence between genetic lineages and
      reproductively isolated taxa in the context of minimal morphological change
      suggests that DNA barcoding will play a leading role in uncovering the hidden
      biodiversity of the oceans and that the sole use of morphologically based
      taxonomy would grossly underestimate the number of marine species.

PMID- 17035168
TI  - Copulation, genital damage and early death in Callosobruchus maculatus.
AB  - Antagonistic sexual coevolution stems from the notion that male and female
      interests over reproduction are in conflict. Such conflicts appear to be
      particularly obvious when male genital armature inflicts damage to the female
      reproductive tract resulting in reduced female longevity. However, studies of
      mating frequency, genital damage and female longevity are difficult to interpret
      because females not only sustain more genital damage, but also receive more
      seminal fluid when they engage in multiple copulations. Here, we attempt to
      disentangle the effects of genital damage and seminal fluid transfer on female
      longevity in the beetle Callosobruchus maculatus (Coleoptera: Bruchidae). Males
      copulating for the sixth time in succession inflicted greater levels of genital
      damage, but transferred smaller ejaculates in comparison with virgin males. The
      number of copulations performed by males was negatively related to female
      fecundity and positively related to female longevity, suggesting a trade-off
      between fecundity and longevity. However, inclusion of fecundity as a covariate
      revealed sperm and/or seminal fluid transfer to have a negative impact on female
      longevity above that caused by the fecundity-longevity trade-off. The
      consequences of multiple copulations on female longevity were examined. Females
      that mated twice laid more eggs and died sooner than those that mated once.
      However, incorporation of fecundity as a covariate into our statistical model
      removed the effect of female mating frequency on female longevity, indicating
      that double-mated females suffer greater mortality owing to the trade-off between
      fecundity and longevity. Males of this species are known to transfer very large
      ejaculates (up to 8% of their body weight), which may represent a significant
      nutritional benefit to females. However, the receipt of large ejaculates appears
      to carry costs. Thus, the interpretation of multiple mating experiments on female
      longevity and associated functional explanations of polyandry in this species are
      likely to be complex.

PMID- 17035169
TI  - Increased genetic diversity as a defence against parasites is undermined by
      social parasites: Microdon mutabilis hoverflies infesting Formica lemani ant
      colonies.
AB  - Genetic diversity can benefit social insects by providing variability in immune
      defences against parasites and pathogens. However, social parasites of ants
      infest colonies and not individuals, and for them a different relationship
      between genetic diversity and resistance may exist. Here, we investigate the
      genetic variation, assessed using up to 12 microsatellite loci, of workers in 91
      Formica lemani colonies in relation to their infestation by the specialist social
      parasite Microdon mutabilis. At the main study site, workers in infested colonies
      exhibited lower relatedness and higher estimated queen numbers, on average, than
      uninfested ones. Additionally, estimated queen numbers were negatively correlated
      with estimated average numbers of mates per queen within infested colonies. At
      another site, infested colonies also exhibited significantly lower worker
      relatedness, and estimated queen numbers were comparable in trend. In contrast,
      in two populations of F. lemani where M. mutabilis was absent, relatedness within
      colonies was high (40 and 90% with R>0.6). While high genetic variation can
      benefit social insects by increasing their resistance to pathogens, there may be
      a cost in the increased likelihood of infiltration by social parasites owing to
      greater variation in nestmate recognition cues. This study provides the first
      empirical test of this hypothesis.

PMID- 17035171
TI  - Social scripts and stark realities: Kenyan adolescents' abortion discourse.
AB  - This study explores students' narratives and discourses about adolescent
      pregnancy and abortion elicited via internet-based open-ended questions posed in
      response to a cartoon vignette. We report on content analysis of recommendations
      and strategies for how to manage the unplanned pregnancy of a fictional young
      couple and in their own personal lives. The responses of 614 young people were
      analysed. Strategies vary widely. They include giving birth, adoption, running
      away, abortion, denial, and postponement until discovery. Young people were also
      queried about unplanned pregnancy resolution among their peers. Discourse
      analysis reveals competing social scripts on abortion. Florid condemnation of
      abortion acts in the hypothetical cases contrasts with more frank and sober
      description of peers' real life abortion behaviour. Students' language is
      compared with that found in official curricula. The rhetorical devices,
      moralizing social scripts and dubious health claims about abortion in students'
      online narratives mirror the tenor and content of their academic curricula as
      well as Kenyan media presentation of the issue. The need for factual information,
      dispassionate dialogue and improved contraceptive access is considerable.

PMID- 17035172
TI  - Process and outcome study of multidisciplinary prosthetic treatment for
      velopharyngeal dysfunction.
AB  - BACKGROUND: A prosthetic approach to velopharyngeal dysfunction (VPD) is not new.
      However, a collaborative interdisciplinary team approach by a speech-and-language
      therapist, dental specialist and maxillofacial technician, including accurate
      fitting using nasendoscopy, has provided an opportunity to define the clinical
      care pathway, and audit the outcomes of this intervention. Systematic outcome
      studies of the effectiveness of prosthetic appliances are few and largely
      anecdotal. AIMS: The aim is twofold: first, to provide a description of the
      process including diagnosis, clinical and technical fabrication; and second, to
      determine the effectiveness of this intervention with nasendoscopy, objective
      blind perceptual analysis of speech data and nasometry. METHODS & PROCEDURES: The
      selection criteria, age, aetiology and process of fabrication are described.
      Thirty-one patients embarked on the programme, but seven patients after initial
      failure or refusal were re-entered into the programme for a second time resulting
      in 38 interventions. At the time of audit, 20 patients had completed the
      treatment, but four of these were inadequately documented. This study reports on
      the 16 patients who successfully completed the programme and who had
      comprehensive records. OUTCOMES & RESULTS: Significant differences were found
      between the pre- and post-treatment evaluations on the speech parameters of
      hypernasality, audible nasal emission and nasometry. CONCLUSIONS: In our centre
      surgery is the first choice of treatment for VPD, but prosthetic management can
      be a useful alternative when this is contraindicated, can be a useful temporary
      solution and can be used to evaluate the potential benefits of surgical
      intervention in some cases. This treatment requires the combined expertise of an
      interdisciplinary team involving the speech-and-language therapist,
      orthodontist/prosthodontist, maxillofacial technician and endoscopist.

PMID- 17035174
TI  - [Study on the relationship between the resistance to MTX and the transport
      protein superfamily of ATP-binding cassette that induces multiple drug
      resistance].
AB  - A major problem, especially the multidrug resistance, in chemotherapy was the
      resistance to the chemotherapeutic agents. ATP-binding cassette transporter
      superfamily that mediated the efflux of drugs was involved in multidrug
      resistance. In order to understand the relationship between the resistance to MTX
      and the transport protein superfamily of ATP-binding cassette, and to investigate
      the mechanism of resistance to MTX, the study detected the expressions of mdr1,
      mrp1, mrp2, mrp3, mrp5, mrp6 and abcg2 that encoded the transport proteins by
      SuperArray analysis and the expressions of MRP1and MRP5 proteins by Western blot
      analysis. The results showed that the multidrug resistance proteins were the
      chief member of ATP-binding cassette transporter superfamily related to
      resistance to MTX. And the high expression levels of mrp1 and mrp5 were detected.
      Moreover, it revealed by SuperArray analysis that expression of mrp5 in MTX
      resistant cells was significantly higher than that in normal mouse cells.
      Besides, corresponding excessive expression of MRP5 protein in MTX-resistant
      cells was also confirmed by Western blot. So, MRP5 could play important roles in
      the resistance to MTX and would be a new potential drug target.

PMID- 17035175
TI  - [Detecting of mtDNA mutations at position A3243G and G3316A in patients with type
      2 diabetes mellitus in Wenzhou].
AB  - To investigate the frequencies of mitochondria DNA (mtDNA) tRNA(Leu (UUR)) point
      mutation A3243G and NADH dehydronase subunit 1(ND1) gene point mutation G3316A in
      Wenzhou area of Zhejiang Province, and to explore the correlation between these
      mutations and the clinical manifestations in patients with type 2 mellitus
      diabetes(T2DM). Two hundreds and forty-four unrelated patients with T2DM and 156
      healthy subjects without family history of T2DM were enrolled in Wenzhou area in
      this study and screened for the point mutations mentioned above with polymerase
      chain reaction (PCR) and restricted fragment length polymorphism(RFLP) analysis.
      The heterogeneous mutations were confirmed with DNA sequencing and denaturing
      high performance liquid chromatography (DHPLC) following T-A cloning of PCR
      products. The percentage of A3243G mutation in group of patients with T2DM and
      control were 0.410% and 0.0% (1/244 vs 0/156), respectively; however, there's not
      any significant difference between these two groups in frequency of A3243G
      mutation (P>0.05). G3316A mutation was detected in 4 of 244 cases with T2DM
      (1.639%) and 2 of 156 healthy controls (1.282%), showing that there's also no
      statistic difference between these two groups in frequency of G3316A mutation
      (P>0.05). It's shown that the frequency of mtDNA tRNA(Leu (UUR)) A3243G mutation
      is fairly low in patients with T2DM in Wenzhou area. Thus it's reasonable to
      assume that this mutation may not be involved in the development and progression
      of T2DM. Furthermore, it's demonstrated that the rate of G3316A mutation of mtDNA
      ND1 gene is rare in patients with T2DM in Wenzhou area and this mutation also
      happened in healthy control. It's suggested that G3316A mutation is just a gene
      polymorphism of mtDNA and not related to the pathogenesis of T2DM.

PMID- 17035176
TI  - [Identification of nine novel alternative splicing isoforms of RHD mRNA].
AB  - To investigate the gene structures of RHD mRNA alternative splicing isoforms,
      total RNA was extracted from normal cord blood samples and RHD mRNA were detected
      using reverse transcription and polymerase chain reaction (RT-PCR) method. The
      PCR products were cloned and directly sequenced. The splicing signals of various
      isoforms were also analyzed by sequencing of exon-intron boundaries using RHD
      gene specific primers, and the expressed sequence tags (ESTs) databank was
      screened to find out other RHD alternative splicing isoforms. Nine novel and
      three recurrent RHD alternative splicing isoforms were identified, among which
      six isoforms were RHD-RHCE hybrid genes. Three types of alternative splicing were
      found including exon skipping, alternative 5' splice sites and alternative 3'
      splice sites. Exons 2 to 9 were involved in RHD mRNA alternative splicing. Two
      other isoforms of intron retention type were also found in human ESTs databank.
      Thus, the mRNA splicing mechanism of RHD gene was very complex, and nine novel
      alternative splicing isoforms were identified including several isoforms based on
      homologous RHD-RHCE hybrid gene.

PMID- 17035177
TI  - [Polymorphism of CGG repeats in the FRAXE fragile site in the Qinba Mountain area
      children and its association with intelligence].
AB  - Variations of CGG repeats in the FRAXE fragile site were determined by PCR
      amplification followed by polyacrylamide gel electrophoresis and sequencing in
      randomly collected Qinba Mountain Area children whose intelligence level was
      determined by China-Wechsler Intelligence Scale for Children (C-WISC).
      Correlations between IQ score and the number of CGG repeats were analyzed.
      Results indicated a difference in the range of CGG repeats among populations from
      different regions, but no difference in the distribution of allele frequency in
      such a population. CGG repeats were not associated with IQ scores in randomly
      collected subjects (r=0.083, P>0.05), in males and females (r(m)=0.225, r(f)=
      0.041, P>0.05), or in subjects with different intelligent levels (F=0.195,
      P>0.05). It can be inferred that variation in the size of CGG repeats was not
      associated with intellectual performance in the Qinba Mountain area children.

PMID- 17035178
TI  - [Relationship between MC4R gene polymorphyism and body weight trait in beagle
      dogs].
AB  - The relationship between MC4R gene polymorphism and body weight in beagle dogs
      was analyzed. Using gene-specific primers based on canine MC4R exonic sequences a
      gene fragment was PCR amplified, cloned and sequenced to identify potential
      polymorphisms. The relationship between a MC4R gene polymorphism detected by PCR
      RFLP and canine body weight was analyzed. Three variants were found in beagle dog
      MC4R DNA sequence, of which two were deletions and one was a transversion which
      created a PshA I site that could be detected by PCR-RFLP. A statistically
      significant relationship between this polymorphism and body weight was found.
      MC4R gene could be a candidate modifier gene for canine body weight.

PMID- 17035179
TI  - [The degree of inbreeding in 10 Chinese indigenous pig breeds].
AB  - The population inbreeding coefficients of 10 indigenous pig breeds were estimated
      by microsatellite markers. Results showed that: the inbreeding coefficient of
      Guizhou miniature pig was the highest (0.1992), and that of Hanzhong black pig
      the lowest (0.0727) among random mating populations. F test showed no significant
      difference in inbreeding coefficient among the 8 breeds (P >0.05). The inbreeding
      coefficient of the Guizhou miniature pig and Bama miniature pig inbreeding lines
      was 0.5907 and 0.4761, respectively.

PMID- 17035180
TI  - [Investigation on bovine leukocyte adhesion deficiency].
AB  - Bovine leukocyte adhesion deficiency (BLAD) is autosomal recessive disease. The
      pathogeny of BLAD is genic mutation of CD18-integrins on the leukocyte. In order
      to know the carrier and occurrence of bovine leukocyte adhesion deficiency (BLAD)
      among cows age from one to six years old in China, 1,000 cows were investigated
      by means of amplifying a CD18 gene fragment via reverse transcriptase-PCR
      followed by restriction digestion with Taq I. Results showed that 19 cows were
      BLAD carriers, indicating that the BLAD carrier rate was 1.9 percent. In
      addition, one cow was found to have BLAD.

PMID- 17035181
TI  - [A molecular phylogeny of Shennongjia white bear based on mitochondrial
      cytochrome b gene sequence].
AB  - The phylogenetic relationship of Shennongjia white bear has been an open
      question. Total DNA was extracted and sequenced from hair and feces of
      Shennongjia white bear. Based on the partial Cyt b gene sequence obtained from
      the samples, the authors aligned them using the Clustal W software program. The
      MEGA software was used to analyze the divergences and base substitutions of the
      partial Cyt b gene among the 11 species: Shennongjia white bear, Selenarctos
      thibetanus, Euarctos americanus, Helarctos malayanus, Ursus arctos, Thalarctos
      maritimus, Melursus ursinus, Procyon lotor, Ailuropoda melanoleuca, Ailurus
      fulgens and Tremarctos ornatus. The phylogenetic trees constructed by multiple
      methods (NJ and MP) supported nearly the same topology. Our molecular results
      show that the sequence divergence between Shennongjia white bear and Asiatic
      black bear (Selenarctos thibetanus) is lower than that between other species.

PMID- 17035182
TI  - [Screening of peafowl microsatellite primers and analysis of genetic diversity].
AB  - The applicability of chicken microsatellite primers to peafowl population was
      analyzed in the present paper, and the results showed 14 of 29 pairs of
      microsatellite primers from chicken could amplify peafowl DNA and produce
      specific allele patterns. A mean of 1.71 alleles was found for each locus. Seven
      pairs were highly polymorphic, and MCW0080 and MCW0098 were ideal markers for
      peafowl. Genetic diversity analysis within and between the green peafowl and the
      blue peafowl populations demonstrated that the expected heterozygosity of two
      peafowl populations were 0.2482 and 0.2744, respectively. The inbreeding index
      (FST), Reynolds' genetic distance and gene flow between the two populations were
      0.078, 0.0603 and 3.896 respectively. These results indicate that the
      heterozygosity and the genetic diversity of these two peafowl populations were
      very low, and suggest a tendency towards intermixing.

PMID- 17035183
TI  - [A research on Ig heavy chain constant region of five Acipenseridae].
AB  - Analyzed the immunoglobulin (Ig) heavy chain constant regions of Russian sturgeon
      (A. gueldenstaedtii); Sterlte sturgeon (A. ruthenus); Amur sturgeon (A.
      schrenckii); Chinese sturgeon (A. sinensis) and Great sturgeon (Huso huso) with
      molecular biology and bioinformatics methods. We cloned IgH nucleic acid
      sequences by RT-PCR using the specific primer, then determined the
      characteristics and functions of the amino acid sequences and plotted out the
      sequence into four sub-regions (CH1-CH4), of which CH4 sub-regions one another
      had the highest identity. According to the analysis of the variation expectation
      value (Kaa), species differentiation time (T) in the CH4 sub-region phylogenetic
      tree, we found that Chinese sturgeon and the theoretical common ancestor of the
      other five sturgeon form the first bifurcation of the tree, while, among the five
      left, Amur sturgeon and Huso sturgeon, Russian sturgeon and Siberian sturgeon,
      Siberian sturgeon (sequence from GenBank), Sterlte itself form another three
      bifurcations respectively. This result can clearly explain the relations of
      taxonomic status, geographical distribution and evolution among the species
      studied.

PMID- 17035184
TI  - [Identification of a common deletion in different curly mutants in Drosophila
      melanogaster].
AB  - Curly is a easily distinguishable dominant mutant wing character. The Cy mutation
      is the most commonly used dominant marker for the second chromosome balancers in
      Drosophila melanogaster, but little is known about the Cy gene. Based on known
      genomic and cytogenetic information, a 102 bp deletion which is located between
      the Genes synaptotagmin (syt) and Activin Like Protein at 23B(Alp23B) on the
      Drosophila melanogaster genome (release 4) had been found to be commonly
      contained on Cy chromosome in three different curly strains. Meanwhile, when
      using the deletion as a DNA marker, the result suggested that Cy homozygote be
      lethal in embryo period. These results will provide some helpful information to
      investigate molecular mechanism of curly wings in the further study.

PMID- 17035185
TI  - [Genetic analysis of two extremely segregation distorted populations in rice
      (Oryza sativa L.)].
AB  - Segregation distortion is a quite common phenomenon in living species and thought
      to be a potent evolutional force. The main reasons of distorted segregation
      ratios are responsible for the selection of gametes or sporophytes. In this
      study, two extreme segregation distortions from the progenies of lmi x 02428 and
      d6 x 93-11 were identified. The segregation ratio of molecular markers tightly
      linked with LMI and D6 genes were analyzed and skew segregation were found in the
      markers tested which were indicated by significant deviation from the expected
      Mendelian segregation ratio(1:2:1). The segregation distorted regions were
      detected between molecular markers ST8 and ST8-2 near the centromere of
      chromosome 8, and ST7-1 and ST7-3 near telomere of chromosome 7, respectively.
      Meanwhile, the results indicated that segregation distortion had related with the
      different crossed combinations.

PMID- 17035186
TI  - [Sequence variation of chloroplast gene infA-rpl36 region occurred in some
      Triticeae species].
AB  - Based on the sequenced wheat chloroplast genome (cpDNA), a pair of primers in
      infA-rp136 region was designed and used to amplify DNA from 12 diploid or
      polyploid Triticeae species. The 12 PCR products were cloned and sequenced. The
      resulting sequences ranged from 584 to 601 bp. DNA sequence analysis revealed
      that variation was higher in their intergenic regions than in their coding
      regions. Among these 12 species, the DNA sequence of coding region of infA gene
      showed homology as high as 97 percent, indicating that the infA gene is highly
      conserved among species. However, substantial deletions and insertions were found
      in 5 out of 12 deduced amino acid sequences, confirming that infA is one of the
      most evolutionally active cpDNA genes. Whereas the low variation was observed in
      rp136 gene, implying that the different genes has different evolutionary speed.
      The constructed phylogenetic trees demonstrate that the polyploidy species
      Thinopyrum intermedium might have different origin of cytoplasm, and their
      cytoplasm origins are as complex as their nuclear genome origins.

PMID- 17035187
TI  - [Genetic analysis of a specially long pod character in artificially resythesized
      Brassica napus L].
AB  - Two hybrid combinations were made with a resynthesized specially-long pod line in
      H218 Brassica napus L., namely H218 x Zhongyou 821, H218 x MSP334 and their six
      generations F(1), F(2), backcrosses B(1) and B(2) and their parents P(1) and P(2)
      were used to study the inheritance of 3 pod related traits, namely the full pod
      length, the pod body length and the pod beak length. The results were the
      followings: the three traits in the F(2) population of the two combinations had a
      continuous normal distribution, indicating that these traits were quantitative in
      nature and controlled by polygenes. The broad-sense heritabilities of the full
      pod length, pod body length and pod beak length of the two combinations were
      65.89%-70.77%, 60.14%-63.38% and 26.36%-46.44%, respectively. The narrow-sense
      heritabilities were 44.01%-46.78%, 46.89%-47.38% and 18.08%-37.87%, respectively.
      The results from the two combinations consistently showed that full pod length,
      pod body length and pod beak length were controlled by 5, 6 and 2 genes
      respectively. The preliminary study on the gene effect demonstrated that the
      three traits in the two combinations all fit the additive-dominant model and the
      epistatic effect was significant. The additive effects and the dominant effects
      of the three traits in the two combinations were both significant. Of the full
      pod length and the pod body length, the dominant effect was more significant than
      the additive effect; and it is the same case for the pod beak length.

PMID- 17035188
TI  - [RNA fingerprinting of the differential expression fragments related to
      cytoplasmic male sterility in Chinese cabbage].
AB  - In order to investigate the differential expression of the genes related to
      cytoplasmic male sterility in Chinese cabbage (Brassica campestris L. ssp.
      Penkinsis), a modified RNA fingerprinting technique was developed to compare the
      difference in the total RNA from flower bud of Chinese cabbage among cytoplasmic
      male sterility (CMS) lines, maintainer lines and F1 hybrids. Four stably
      differential fragments S47-412, S93-622, S176-343 and S199-904 were amplified,
      cloned and sequenced with primers selected from 186 random primers. Based on the
      nucleotide sequence of the four differential fragments, four pairs of specific
      primers were designed to validate the differential fragments. The validation
      showed S47-412 and S93-622 were false positives and S176-343 and S199-904 were
      confirmed by PCR with the specific primers. Sequence analysis revealed that both
      of two differential fragments had strong homology with the nucleotide sequence of
      orf224/atp6 site of Polima CMS and the nucleotide sequence of S176-343 and S199
      904 had a superposed region. All these indicate that the two fragments probably
      have strong relationship with cytoplasmic male sterility in Chinese cabbage.

PMID- 17035189
TI  - [Cloning and diversity analysis of microorganism genes from alkalescence soil].
AB  - The metagenomic DNAs were extracted and purified from alkalescence environmental
      samples directly. On the basis of the metagenomic DNA, the alkaline soil 16S rDNA
      library composed of 5,562 positive clones was constructed. The phylogenic tree
      indicated that the bacteria from the alkaline soils were bio-diversity. The
      metagenomic DNA library named AL01 was constructed by inserting restriction
      fragments of the purified DNAs into plasmids pGEM-3Zf(+) vector. This library
      contained 23,650 positive clones and the average foreign DNA fragments were about
      3.2 kb. The length of the library covered 75.68 Mb. The efficiency of the
      metagenomic library was approximately 6,000 clones from 1g dry soil samples.
      After screening AL01 DNA library with the screening tactics of enzymes, we
      confirmed that a positive clone, designated pGXAA2011, contained an alkaline
      protease gene AP01. Enzymatic analysis proved that its reaction optimum pH was
      9.5 and the optimum temperature was 40 degrees C. Furthermore, a clone,
      designated pGXAG142 was screened from metagenomic DNA library, which expresses
      beta-glucosidase. DNA sequence indicated that the potential ORF of pGXAG142,
      which was named unglu01, there was no DNA or amino acids identity with the known
      beta-glucosidase genes in the Genbank. The integrated ORF was cloned into pETBlue
      2 vector and was then transformed into Tuner(DE3)pLacI. The recombinant
      expression clone could express beta-glucosidase on the screening plate clearly
      and the analysis of SDS-PAGE indicated that the target protein was about 29 kDa.

PMID- 17035190
TI  - [Identification of the gene correlated with salt stress in the Saccharomyces
      cerevisiae 263-H9 mutant].
AB  - The mutant 263-H9 with hypersensitivity to several stress conditions (1.5 mol/L
      Sorbitol, 0.65 mol/L NaCl and 15 degrees C) was obtained by using transposon
      mutagenesis in the Saccharomyces cerevisiae strain W303-1A. Unlike other mutants
      the transposon in 263-H9 was intergenic between GIP2 and YER053C-A. Using gene
      knockout, a yeast genomic library and other methods, the gene correlated with the
      salt stress response was identified. The data indicated that the phenotype of 263
      H9 was not directly caused by the insertion of the transposon. On the other hand,
      the hypersensitivity to salt and other stress conditions was due to the deletion
      of 5 base pairs close to position 936 bp in the PBS2 gene essential for HOG
      signal pathway regulation under salt stress.

PMID- 17035191
TI  - [A novel method of the genome-wide prediction for the target genes and its
      application].
AB  - Based on the protein databases of several model species, this study developed a
      new method of the Genome-wide prediction for the target genes, using Hidden
      Markov model by Perl programming. The advantages of this method are high
      throughput, high quality and easy prediction, especially in the case of multi
      domains proteins families. By this method, we predicted the PPR and TPR proteins
      families in whole genome of several model species. There were 536 PPR proteins
      and 199 TPR proteins in Oryza sativa ssp. japonica, 519 PPR proteins and 177 TPR
      proteins in Oryza sativa L. ssp. indica, 735 PPR proteins and 292 TPR proteins in
      Arabidopsis thaliana, 6 PPR proteins and 32 TPR proteins in Cyanidioschyzon
      merolae. Synechococcus and Thermophilic archaebacterium did not have PPR
      proteins. By contrast, 10 TPR proteins were found in Synechococcus and 4 TPR
      proteins were found in Thermophilic archaebacterium. Moreover, of these results,
      some further bioinformatics analyses were conducted.

PMID- 17035192
TI  - [Studies of methods and exploitation of computer software for mapping interactive
      genes].
AB  - There are six possible types of gene interaction in qualitative traits, namely,
      complementary, duplicate, cumulative, dominant epistasis, recessive epistasis and
      inhibiting. In genetic studies, the problem of mapping interactive genes may be
      met sometimes, but no systematic researches on the methodology and computer
      software for the mapping of interactive genes have been reported up to date. In
      this paper, methods for the mapping of interactive genes based on maximum
      likelihood estimation and corresponding computer software (IGMapping 1.0) are
      presented. Computer simulations have shown that the methods proposed can
      unbiasedly estimate the recombination frequency or linkage distance between a
      codominant marker and an interactive gene.

PMID- 17035193
TI  - [Research advances in expression profiling of mitochondrial proteins].
AB  - As an important subcellular organelle, the mitochondrion plays an important role
      in many physiological and pathological processes. This article reviews the most
      recent studies in the significance, technological aspects, problems and future
      prospects of expression profiling of mitochondrial proteins.

PMID- 17035194
TI  - [Research progress on X chromosome STR loci in forensic medicine].
AB  - This article summarizes the structure and hereditary characteristics of X
      chromosome, research progress of using multiplex PCR system to amplify X
      chromosome specific short tandom repeat (X-STR) loci and its forensic
      applications. It also presents the advantages and disadvantages of X-STR loci in
      the practice of forensic medicine, with an aim to promote wider use of X-STR loci
      in forensic science.

PMID- 17035195
TI  - [Progress in research of chitosan as a non-viral gene delivery vector].
AB  - Efficiency of non-viral gene delivery based on chitosan and chitosan derivatives
      as DNA condensing carrier is dependent on a series of factors, such as complex
      size, the charge ratio of chitosan/DNA, molecular mass of chitosan, the degree of
      chitosan deacetylation, pH and serum concentration of the transfection medium.
      Through modifying the chitosan in a certain extent, we can change the efficiency
      of transfection. Studies on transfection condition, efficiency and mechanism
      using chitosan and chitosan derivatives as transfection agents are reviewed.

PMID- 17035196
TI  - [Application of laser capture microdissection in plant genomic research].
AB  - To a large degree, the growth and development of plants depend on the organ
      and/or cell type-specific expression of genes. However, it can be difficult to
      obtain sufficient number of specific cells from any developmental stage to
      analyze expression of genes. Laser capture microdissection (LCM) is a novel
      technique that allows us to collect pure targeted cell subgroup or even a single
      cell quickly and precisely, thus the problem of tissue heterogeneity in molecular
      analysis can be resolved successfully. In this paper, the principles of LCM were
      introduced and the application of LCM in plant was summarized in gene expression
      analysis, proteomics and plant-microbe interaction. Meanwhile, possible
      directions of LCM in plant were put forward.

PMID- 17035197
TI  - [Polyketides obtained using metagenome library technique].
AB  - Polyketides are an important class of bioactive secondary metabolites. Since the
      recurrence of the known polyketides is very high during the discovery of novel
      natural polyketide compounds using traditional methods, new approaches are
      developed for the biosynthesis of these compounds. This review discusses
      discovery of new polyketides via metagenome library technique.

PMID- 17035198
TI  - [The function of F-box protein in plant growth and development].
AB  - Ubiquitin-mediated proteolysis is involved in many biological processes in
      eukaryotes. SCF complex is a very important ubiquitin E3 ligase which has been
      exploited very well in plants. F-box protein characterized by an F-box motif is a
      subunit of SCF complex, which works as determinant in substrate recognition.
      Currently, many F-box proteins have been identified in plants which are involving
      in hormone (e.g., ethylene, auxin, gibberellin and jasmonate ) signal
      transduction and biological processes, such as self-incompatibility and floral
      development. F-box proteins may also participate stress response in plants.
      Recent study suggested that the Arabidopsis F-box protein TIR1 is an auxin
      receptor. Therefore, F-box protein mediated proteolysis may be an important gene
      expression mechanism in plants.

PMID- 17035199
TI  - Whither veterinary education--have we lost our direction?

PMID- 17035200
TI  - Faculty development: principles and practices.
AB  - Instructors in the health professions today must acquire knowledge and
      competencies that go beyond disciplinary expertise. It is now generally accepted
      that educational training as a teacher is essential to a faculty member's
      effectiveness as an educator. The educational challenges across the health
      professions share many similarities. In this article, we draw on the medical
      education literature and focus on faculty development designed to enhance
      teaching effectiveness. We first address commonly included faculty development
      topics, including instructional improvement, organizational development, the
      development of professional academic skills, and the teaching of specific content
      areas. We then review a variety of educational approaches and formats that are
      described in the literature. Included in this discussion are commonly used
      workshops, seminars, short courses, and fellowships, as well as longitudinal
      programs, peer coaching, mentorship, self-directed learning, and computer-aided
      instruction. We also briefly explore learning at work and in communities of
      practice, and we discuss several frequently encountered challenges in designing
      and implementing faculty development activities, including motivating colleagues
      and assessing program effectiveness. We conclude the discussion by presenting a
      set of guidelines for the design of effective faculty development programs.

PMID- 17035202
TI  - Historical perspective of zoo and wildlife medicine.
AB  - Setting the stage for the other 12 articles on Zoological Medical Education in
      this theme of articles in the Journal of Veterinary Medical Education, this
      article provides a brief historical perspective on the foundation of this
      discipline.

PMID- 17035203
TI  - Current perspectives on curriculum needs in zoological medicine.
AB  - Advances have been made in expanding veterinary curricula to deliver basic key
      knowledge and skills necessary for provision of health care to captive and
      companion non-domestic or non-traditional species in the veterinary colleges of
      the United States and Canada. These advances were in large part facilitated by
      the deliberations and recommendations of the White Oak Accords. Though a five
      year review of curricular opportunities at US and Canadian veterinary colleges
      shows that progress has been made in implementing the recommendations of the
      White Oak Accords, there remains room for improvement. The broadly comparative
      and health-maintenance basis of zoological medicine contributes critically to the
      potential for veterinary medicine to make important contributions to the concept
      of the integrated health of the planet. Emergence of key zoonotic and production
      animal diseases derived from and within wildlife populations since 2000 has
      increased awareness worldwide of the importance of zoological medicine in
      protecting both production livestock and public health. These areas are addressed
      in elective curricula at colleges emerging as centers of excellence in zoological
      medicine, but it is critical that core curricula in zoological medicine at all
      schools be strengthened to include these important areas to prepare our DVM/VMD
      graduates to protect companion-animal, production-animal, and public health.

PMID- 17035204
TI  - Historical perspective and future directions in training of veterinary
      pathologists with an emphasis on zoo and wildlife species.
AB  - This article discusses the history of the field of zoo and wildlife pathology,
      training opportunities for veterinary students and graduate veterinarians, and
      current and future job opportunities. The niches occupied by veterinarians in
      this field and their contributions to animal and human health are also
      highlighted. The field of zoo and wildlife, or "non-traditional" species,
      pathology has its roots in comparative anatomy, zoology, wildlife biology, and
      medical pathology in the mid- to late nineteenth century. The initial emphasis
      was on comparisons between animal and human diseases or on management of game
      animals. Veterinarians became increasingly involved during the twentieth century,
      gradually changing the emphasis to improvement of conservation strategies,
      captive care, and elucidation of diseases of concern for the animals themselves.
      Currently there are several zoos and wildlife agencies in the United States
      employing full-time veterinary pathologists. Private and government diagnostic
      laboratories, veterinary schools, and other academic institutions in the United
      States with pathology departments are other employers. The field requires post
      DVM training by means of a residency program leading to board certification,
      graduate school (MS or PhD degrees), or both. Veterinary students can gain
      valuable experience in the field through externships and, at some schools,
      through elective courses in the curriculum. Current concerns about ecosystem
      health, bioterrorism, and the recognition that captive and free-ranging wildlife
      can serve as sentinel species will increase the demand for veterinary
      pathologists choosing this very rewarding career path specializing in non
      traditional species.

PMID- 17035205
TI  - Zoological medicine and public health.
AB  - Public-health issues regarding zoological collections and free-ranging wildlife
      have historically been linked to the risk of transmission of zoonotic diseases
      and accidents relating to bites or injection of venom or toxins by venomous
      animals. It is only recently that major consideration has been given worldwide to
      the role of the veterinary profession in contributing to investigating zoonotic
      diseases in free-ranging wildlife and integrating the concept of public health
      into the management activities of game preserves and wildlife parks. At the
      veterinary undergraduate level, courses in basic epidemiology, which should
      include outbreak investigation and disease surveillance, but also in population
      medicine, in infectious and parasitic diseases (especially new and emerging or re
      emerging zoonoses), and in ecology should be part of the core curriculum. Foreign
      diseases, especially dealing with zoonotic diseases that are major threats
      because of possible agro-terrorism or spread of zoonoses, need to be taught in
      veterinary college curricula. Furthermore, knowledge of the principles of ecology
      and ecosystems should be acquired either during pre-veterinary studies or, at
      least, at the beginning of the veterinary curriculum. At the post-graduate level,
      master's degrees in preventive veterinary medicine, ecology and environmental
      health, or public health with an emphasis on infectious diseases should be
      offered to veterinarians seeking job opportunities in public health and wildlife
      management.

PMID- 17035206
TI  - Educating veterinarians for careers in free-ranging wildlife medicine and
      ecosystem health.
AB  - In the last 10 years, the field of zoological medicine has seen an expansive
      broadening into the arenas of free-ranging wildlife, conservation medicine, and
      ecosystem health. During the spring/summer of 2005, we prepared and disseminated
      a survey designed to identify training and educational needs for individuals
      entering the wildlife medicine and ecosystem health fields. Our data revealed
      that few wildlife veterinarians believe that the training they received in
      veterinary school adequately prepared them to acquire and succeed in their field.
      Wildlife veterinarians and their employers ranked mentorship with an experienced
      wildlife veterinarian, training in leadership and communication, courses and
      externships in wildlife health, and additional formal training beyond the
      veterinary degree as important in preparation for success. Employers, wildlife
      veterinarians, and job seekers alike reported that understanding and maintaining
      ecosystem health is a key component of the wildlife veterinarian's job
      description, as it is critical to protecting animal health, including human
      health. Today's wildlife veterinarians are a new type of transdisciplinary
      professional; they practice medicine in their communities and hold titles in
      every level of government and academia. It is time that we integrate ecosystem
      health into our curricula to nurture and enhance an expansive way of looking at
      veterinary medicine and to ensure that veterinary graduates are prepared to excel
      in this new and complex world, in which the health of wildlife, domestic animals,
      and people are interdependent.

PMID- 17035207
TI  - Future directions in training veterinarians for companion avian species.
AB  - Companion avian medicine has become a routine part of veterinary practice. More
      than 16 million companion birds are owned by approximately 6.4 million US
      households. This report outlines suggested undergraduate veterinary curricula,
      opportunities for post-graduate education, and options for training avian
      veterinarians.

PMID- 17035208
TI  - A model for teaching raptor medicine in the veterinary curriculum.
AB  - Injured or sick wild avian species, especially raptors (birds of prey, including
      hawks, owls, falcons, and eagles), can present different challenges to veterinary
      students and veterinarians who are trained in companion avian medicine (e.g.,
      parrot medicine). Proper capture and restraint, feeding, housing, and certain
      diagnostic and treatment techniques involving raptors require different skills,
      knowledge, and resources than working with parrots. We developed an innovative
      raptor medicine program that enables students to acquire proficiency in safe
      capture, restraint, and examination techniques and in common diagnostic and
      treatment procedures. A self-assessment survey was developed to determine
      students' confidence and proficiency in 10 procedures taught in the lab. Groups
      were compared by class status (Year 1 vs. Year 2 and 3) and level of prior raptor
      experience (non-experienced or experienced). In surveys conducted before and
      after teaching two sets of raptor training labs, students rated themselves
      significantly more proficient in all 10 diagnostic and treatment procedures after
      completing the two raptor laboratories. The greatest improvements were observed
      in technical skill procedures such as fluid administration, intramuscular
      injections, cloacal swabs, venipuncture, and bandaging. Our approach to
      incorporating elective wildlife learning experiences into the veterinary
      curriculum may be replicable in other veterinary schools, with or without a
      wildlife rehabilitation program.

PMID- 17035209
TI  - Future directions in reptile medical education.
AB  - Reptile medicine has emerged as a specialty area within the broader field of
      zoological medicine. It encompasses the medical needs of approximately 7,500
      vertebrate species. This vertebrate class is highly diversified, having
      biological and medical peculiarities that differ both between and within major
      groups. Historically, veterinarians who have become recognized specialists with
      reptiles have had limited formal training in their medical management. The pet
      reptile trade is a multi-million-dollar business, and the popularity of reptiles
      as pets has resulted in a need for more veterinarians with training in their
      medical management. While few private practices have high volumes of reptile
      cases, many small-animal practices will have the opportunity to see a significant
      number of reptiles on an annual basis. Most practitioners with reptile medical
      expertise have merged their experiences as reptile pet owners with the principles
      of veterinary medicine taught in veterinary college. Several North American
      veterinary colleges have reptile medicine courses, and most have didactic and
      clinical courses in exotic and zoo animal medicine that include lectures and
      practical experience. Most accredited zoological medicine residency training
      programs include training in reptile medicine. The case load and interest in
      reptile medicine will probably never be sufficient to lead the average veterinary
      college to develop much more than what is currently offered. Consequently, those
      few colleges having more extensive course offerings, both didactic and clinical,
      will serve as educational centers for this discipline. Future Web-based teaching
      programs in reptile medicine will allow students nationally and internationally
      to have access to instructional material that can be continually updated.

PMID- 17035210
TI  - Future directions in training of veterinarians for small exotic mammal medicine:
      expectations, potential, opportunities, and mandates.
AB  - Small exotic mammals have been companions to people for almost as long as dogs
      and cats have been. The challenge for veterinary medicine today is to decipher
      the tea leaves and determine whether small mammals are fad or transient pets or
      whether they will still be popular in 20 years. This article focuses on pet small
      mammal medicine, as the concerns of the laboratory animal are better known and
      may differ profoundly from those of a pet. Dozens of species of small exotic
      mammals are kept as pets. These pet small-mammal species have historically served
      human purposes other than companionship: for hunting, for their pelts, or for
      meat. Now, they are common pets. At present, most veterinary schools lack courses
      in the medical care of these animals. Veterinary students need at least one
      required class to introduce them to these pets. Currently, there are no small
      mammal-only residency programs. This does not correspond with current needs. The
      only way to judge current needs is by assessing what employers are looking for.
      In a recent JAVMA classified section, almost 30% of small-animal practices in
      suburban/urban areas were hiring veterinarians with knowledge of exotic pets. All
      veterinarians must recognize that pet exotic small mammals have changed the
      landscape of small-animal medicine. It is a reality that, today, many small
      animal practices see pet exotic small mammals on a daily basis.

PMID- 17035211
TI  - Future directions in training zoological medicine veterinarians.
AB  - The American College of Zoological Medicine (ACZM) is dedicated to excellence in
      furthering the health and well-being of both captive and free-ranging wild
      animals. Currently there are 14 ACZM-approved residency programs in zoological
      medicine. In addition, eight non-approved residencies and 15 internships in North
      America provide training opportunities in this field. This article outlines some
      of the training opportunities for both veterinary students and graduate
      veterinarians that would best position them for entry into a zoological medicine
      training program. Although there is a growing number of opportunities for
      individuals to serve in captive and free-ranging wildlife health positions,
      existing training programs are inadequate to meet these needs. It is also
      acknowledged that there is an increasing number of veterinary students entering
      veterinary schools with an interest in zoological medicine and that the job
      market is still limited. However, positions and opportunities in zoological
      medicine are available for those individuals with the drive, dedication, and
      passion to succeed.

PMID- 17035212
TI  - The future of training for aquatic animal health veterinarians.
AB  - This article describes educational approaches for training veterinary students,
      veterinary graduates, and practicing veterinarians in the area of aquatic animal
      health and lists a range of general research, training, internship/residency, and
      continuing-education resources.

PMID- 17035213
TI  - Zoological medicine education in Canada: options and opportunities.
AB  - Canada has four veterinary schools, from which approximately 325 veterinarians
      graduate each year. Curricular offerings in zoological medicine consist of
      limited core material and a variety of internal and external electives pursued by
      students with particular interests. Several electives are offered jointly by and
      rotate among the existing schools. All schools offer graduate programs that
      encompass some aspects of zoological medicine. A fifth veterinary school,
      expected to open in 2007, will have a stronger focus on ecosystem health and
      zoological medicine. In Canada, the most effective method of increasing
      educational opportunities in zoological medicine is likely through enhanced
      collaboration among the five schools. Employment opportunities exist in private
      veterinary practice and at universities, research establishments, provincial or
      federal governments, and zoological gardens and safari parks. Increasing
      recognition of the importance of ecosystem health and of the relevance of
      wildlife diseases to public and domestic animal health will likely result in
      additional opportunities for veterinarians with an interest in and knowledge of
      zoological medicine.

PMID- 17035214
TI  - Zoo and wildlife medical education: a European perspective.
AB  - Europe has a long and distinguished history in veterinary science and education,
      and it was here that the first professional investigations of pathological
      conditions in zoo animals took place. However, despite an increasing number of
      veterinarians working with wildlife, education in zoological and wildlife
      medicine has only recently become part of formal veterinary training at the
      undergraduate level. Consequently, current educational opportunities in
      zoological and wildlife medicine vary widely throughout Europe, both in
      availability and in composition. The need to establish agreed standards in
      education across Europe and to foster the mobility of students and teaching staff
      are reflected by international agreements such as the Bologna Treaty and the
      ERASMUS-SOCRATES program. Europe is also home to a number of voluntary
      professional organizations, such as the European Wildlife Disease Association and
      the European Association of Zoo and Wildlife Veterinarians, that actively promote
      the inclusion of zoological and wildlife medicine in veterinary education. Zoo
      and wildlife medicine is currently a veterinary specialization in Europe, but
      educational opportunities are likely to increase in availability in the future.

PMID- 17035215
TI  - Global public health issues.
AB  - The context of the conference presentation that gave rise to this article was the
      importance of veterinarians becoming more engaged in the public-health challenges
      of today. During the presentation, I sought to point out some of the pressing
      reasons why. Of particular concern to me are the missed opportunities to help
      influence human health and well-being as private veterinary practitioners in
      addition to public-practice veterinarians. Key elements: Public health, the
      protection and improvement of community health by organized community effort; the
      global community, the entire world; social responsibility, being, as members of
      society, morally and legally responsible for the welfare of human beings;
      terrorism, the systematic use of terror (fear), especially as a means of coercion
      (it is always local!); system integration, the interaction of interdependent
      groups to form a unified whole.

PMID- 17035216
TI  - The global veterinarian: the why? The what? The how?
AB  - Globalization has created an entirely new landscape for veterinarians.
      Opportunities abound to meet the formidable challenges presented as animals,
      people, and microbes travel at a previously unimagined speed, fueled by the
      engine of commerce, resulting in a plethora of new diseases, issues, and
      partnerships. Re-tooling our profession to ensure that we can continue to fulfill
      our veterinary oath in the face of these changes will require both short- and
      long-term changes. It is essential that a single overarching, non-affiliated
      organization be formed to tie together all entities, providing the structure to
      create needed synergy to enhance our currently fragmented professional responses
      and to solicit funds to effect necessary changes.

PMID- 17035217
TI  - Global veterinary opportunities and responsibilities: some recent graduates'
      perspectives.
AB  - The veterinary profession has critical global responsibilities. To help meet
      these responsibilities, it is critical that the training programs for veterinary
      graduates provide them with the skills, knowledge, understanding, and
      professional attributes pertinent to meeting these responsibilities. The programs
      at US veterinary schools, in the full range from admissions, to curriculum, to
      post-graduate opportunities, fall short in many critical arenas.

PMID- 17035218
TI  - Veterinary medicine educational requirements to meet the needs of the US Agency
      for International Development.
AB  - The US Agency for International Development (USAID) works within the overall
      purpose of US foreign assistance to improve the lives of the citizens of the
      developing world. Through partnerships with other agencies, organizations, and
      governments, and using its field offices around the world, USAID strives to
      develop local capacity and thus build sustainable development. Two specific USAID
      programs pertinent to veterinary medicine are global health and agriculture. In
      the area of global health, veterinarians can aid USAID's work to improve the
      quality, availability, and use of essential health services that specifically
      target maternal and child health, HIV/AIDS, family planning and reproductive
      health, infectious diseases, environmental health, nutrition, and other life
      saving areas. The challenge of making the agricultural sector in a developing
      country more productive is a critical one for USAID and a clear area for input
      from the veterinary profession. Animal agriculture is the largest single sector
      of agricultural economies in most developing countries, and livestock remains a
      critical component of poverty alleviation. There are educational requirements
      that benefit anyone working at USAID and can be met prior to admittance to a DVM
      program, as part of a DVM curriculum, or in post-graduate training/employment,
      such as proficiency in a foreign language; environmental sciences background;
      familiarity with accounting and management techniques; expertise in foreign
      animal diseases, zoonotic diseases, epidemiology, food safety, and nutrition, as
      well as the application to human health of those areas; an advanced degree such
      as an MPH; and management experience. Appropriately trained veterinarians can
      make enormous contributions to USAID's global efforts to improve the health and
      agriculture sectors of developing nations.

PMID- 17035219
TI  - The US Army Veterinary Corps: a model for professional career development with a
      public health and global perspective.
AB  - The US Army Veterinary Corps is composed of approximately 420 active-duty and 200
      reserve-component veterinary officers, with 40 to 45 new veterinarians joining
      the active ranks each year. This article briefly summarizes the training that
      members of the veterinary corps receive in preparation for their diverse range of
      duties in service to the United States.

PMID- 17035220
TI  - Increased student self-confidence in clinical reasoning skills associated with
      case-based learning (CBL).
AB  - Second-year veterinary students were surveyed at the beginning and end of a 15
      week semester regarding their confidence in performing three clinical reasoning
      skills: (1) making Problem Lists; (2) making Rule-Out Lists; and (3) selecting
      appropriate diagnostic tests. Each week during the semester, these skills were
      practiced in small-group case discussions. Changes in self-confidence were
      analyzed and studied in light of faculty assessments of student competence in
      performance of the three skills. RATIONALE: The purpose of the study was to
      determine if students' self-confidence in performing three clinical reasoning
      skills increased with practice. METHODOLOGY: On the first and last days of class,
      students rated their confidence in each of the three skills on a scale of 0 to
      10. Mean confidence scores for the whole class both for time points and for each
      of the three skills were analyzed. RESULTS: There were significant increases in
      students' self-confidence in all three clinical reasoning skills over the
      semester each year. A greater percentage of students expressed improved
      confidence in selecting appropriate diagnostic tests than in the other two skills
      in three of the four years studied. CONCLUSIONS: Students' self-confidence in
      performing three clinical reasoning skills improved over the course of a semester
      in which they practiced the skills in a CBL format. Subjective faculty assessment
      of students' competence in these skills generally indicated improvement. However,
      no meaningful conclusions about the correlation of skill competence and student
      confidence could be drawn because of inadequacies in the measurement of student
      performance.

PMID- 17035221
TI  - Predictors of depression and anxiety in first-year veterinary students: a
      preliminary report.
AB  - Historically, veterinary medical students' mental health has rarely been
      investigated, but recently there has been renewed interest in this topic. The
      present study evaluated depression and anxiety levels in a cross-sectional
      investigation of 93 first-year veterinary medical students enrolled at Kansas
      State University (KSU). During their first semester, students completed the
      Center for Epidemiological Studies Depression Scale (CES-D) and the Mental Health
      Inventory's Anxiety Scale (MHI-A). Results indicate that 32% of these first-year
      KSU veterinary students were experiencing clinical levels of depressive symptoms.
      Additionally, students reported elevated anxiety scores. Predictors of depression
      and anxiety levels include homesickness, physical health, and unclear instructor
      expectations. Areas of intervention with a focus on improving veterinary medical
      student well-being are discussed.

PMID- 17035222
TI  - Forecasting veterinary school admission probabilities for undergraduate student
      profiles.
AB  - Increased competition for veterinary school admission has created a need to
      determine whether individual students are likely to be successful candidates for
      veterinary school admission early in their undergraduate careers. Students invest
      considerable time and money in pre-veterinary courses of study, hoping for
      acceptance into professional veterinary school. A forecasting model was developed
      to predict the likelihood of students with particular characteristics gaining
      acceptance. Characteristics such as gender, age, size of high school, and ACT,
      are known upon entrance into college and can be used to determine the likelihood
      of an individual's being accepted. Data were gathered from the Louisiana State
      University College of Veterinary Medicine (LSU-CVM) admissions for all students
      applying to veterinary school for the classes of 2006 through 2008 from the top
      two agricultural programs in the state in terms of quantity of applicants to
      veterinary school: Louisiana State University and Louisiana Tech University. A
      one-way ANOVA was used to examine whether there were any statistical differences
      between known demographic and performance variables and acceptance into
      veterinary school. A logit forecasting model was then estimated to predict the
      likelihood of gaining acceptance into veterinary school based only on variables
      known early in the student's undergraduate career. Age, gender, and ACT scores
      were determined to be important variables in determining the likelihood of
      gaining admission. Overall, the forecasting model is of use in assigning
      probabilities of acceptance into veterinary school for specific student profiles,
      which can assist in one-on-one assistance from advisor to student.

PMID- 17035223
TI  - Evaluation of traditional instruction versus a self-learning computer module in
      teaching veterinary students how to pass a nasogastric tube in the horse.
AB  - OBJECTIVE: To evaluate the effectiveness of a self-learning computer module
      (SLCM) versus traditional instruction in teaching how to pass a nasogastric tube
      (NG) in the horse. DESIGN: A double-blind, monocentric study. SAMPLE POPULATION:
      52 third-year students in the DVM program were randomly assigned to two groups:
      traditional instruction (N = 25) or SLCM instruction (N = 27). PROCEDURE:
      Traditional instruction consisted of an instructor and live demonstration; SCLM
      students were given a CD-ROM each. Both sessions lasted one hour. The students
      were then united in one session to practice passing the NG tube. Their
      performance was videotaped and evaluated by two evaluators. Students were then
      given a multiple-choice knowledge quiz. One week later, a second demonstration of
      the same procedure by the two methods was administered, and students were allowed
      to choose either method of instruction. A Likert-scale questionnaire about their
      comfort, their confidence, and the appropriateness of the teaching method was
      given after the second demonstration. Data were analyzed by non-parametric tests.
      A focus-group study was conducted to determine students' perception of each
      teaching method. Nine participants in the experiment volunteered for these focus
      group sessions. The sessions were audiotaped and transcribed. RESULTS: Students
      in the SLCM group performed significantly better on the test of knowledge than
      traditionally instructed students. The questionnaire found significant perceived
      benefits to computer-based instruction, including a preference for the computer
      based module, better learning, and greater preparedness. In hands-on skill, time
      to pass the NG tube on the successful attempt was significantly shorter in the
      SLCM group than in the traditionally instructed group. The data from focus-group
      sessions suggest that while participants expressed satisfaction with both modes
      of instruction, the SLCM group reported somewhat higher levels of confidence in
      their skills prior to performing the procedure. Whereas the traditional group
      reported a strong preference for continued live demonstrations of the procedure,
      the SLCM group stated that the computer-assisted module alone provided them with
      effective instruction. CONCLUSION: Computer-assisted learning is an acceptable
      and effective method of training students to pass an NG tube with potential
      welfare, proficiency, and knowledge advantages.

PMID- 17035224
TI  - A comparison of linear, fixed-form computer-based testing versus traditional
      paper-and-pencil-format testing in veterinary medical education.
AB  - Computerized testing has made significant inroads into veterinary education.
      Traditional paper-and-pencil examination formats are being replaced by computer
      based testing (CBT). Computer-administered, fixed-form tests, because they mimic
      most closely the familiar fixed-response paper-and-pencil test formats, might
      intuitively seem to be inherently equivalent to their paper-and-pencil
      counterparts. However, research examining test-mode effects on student
      performance presents a very mixed picture. Additionally, students often report
      that they feel their performance is adversely affected by CBT and that their
      grades on the computer-based exams are lower than they would have been on the
      more familiar paper-and-pencil format. In order to address student perceptions of
      negative impact and the mixed nature of the published research results on the
      topic, a study was conducted to assess whether the transition from paper-and
      pencil to equivalent linear CBT exams did, in fact, affect students' examination
      scores. This study found no evidence for significant test-mode effects on student
      scores as a result of the introduction of computer-based testing into the
      veterinary curriculum.

PMID- 17035225
TI  - An electronic instructor for gross anatomy dissection.
AB  - Gross anatomy is time consuming to teach and to learn. Because the process of
      dissection takes up so much student time, assistance in the form of an in-lab
      instructional DVD program might improve student performance. The DVD could be
      viewed with a portable device by individual dissection groups at their tables.
      Groups could dissect at their own pace, with access to step-by-step
      demonstrations and answers to frequently asked anatomical questions. We created
      an instructional DVD program demonstrating dissection of the canine ventral neck
      and thoracic limb. The effect on student exam scores of using the DVD versus not
      using it was measured in a controlled, two-sample study using incoming first-year
      veterinary students as volunteers. Volunteers were told the study was of two
      different dissection methods; the DVD was not specifically mentioned until after
      the students were separated into two groups (Blue/DVD group and Orange/No DVD
      group), and then only to volunteers in the Blue group. Except for the DVD, the
      two groups had the same resources. The difference in scores on an exam given
      after a single dissection period did not differ sufficiently to conclude that DVD
      use raised the mean score; however, 73% of the DVD group scored 60% or higher,
      while only 38% of the No DVD group scored 60% or higher. The difference in mean
      scores overall was 2.3 points out of a possible 49, suggesting that the DVD
      helped students, especially those with lower scores, to earn two to three more
      points than they would have otherwise.

PMID- 17035226
TI  - Learning evidence-based veterinary medicine through development of a critically
      appraised topic.
AB  - Evidence-based veterinary medicine is a relatively new field of study. Increased
      knowledge of medicine coupled with the increased ability of computers and other
      electronic devices present overwhelming information. The critically appraised
      topic (CAT) is one method to gather and evaluate information related to a
      clinical question. CATs in informatics are short summaries of evidence, usually
      found through literature searches, in response to a specifically stated,
      clinically oriented problem or question. This article describes a study in which
      each first-year veterinary student developed a CAT as a class project. The
      results of this project indicate that students were able to successfully develop
      CATs and that this exercise helped them understand evidence-based veterinary
      medicine concepts. Though some modification in this project will be made in the
      future, overall it was a worthwhile effort and will remain as an activity in the
      course.

PMID- 17035227
TI  - Membrane topology and identification of key functional amino acid residues of
      murine acyl-CoA:diacylglycerol acyltransferase-2.
AB  - Triacylglycerols are the predominant molecules of energy storage in eukaryotes.
      However, excessive accumulation of triacylglycerols in adipose tissue leads to
      obesity and, in nonadipose tissues, is associated with tissue dysfunction. Hence,
      it is of great importance to have a better understanding of the molecular
      mechanisms of triacylglycerol synthesis. The final step in triacylglycerol
      synthesis is catalyzed by the acyl-CoA:diacylglycerol acyltransferase (DGAT)
      enzymes, DGAT1 and DGAT2. Although recent studies have shed light on metabolic
      functions of these enzymes, little is known about the molecular aspects of their
      structures or functions. Here we report the topology for murine DGAT2 and the
      identification of key amino acids that likely contribute to enzymatic function.
      Our data indicate that DGAT2 is an integral membrane protein with both the N and
      C termini oriented toward the cytosol. A long hydrophobic region spanning amino
      acids 66-115 likely comprises two transmembrane domains or, alternatively, a
      single domain that is embedded in the membrane bilayer. The bulk of the protein
      lies distal to the transmembrane domains. This region shares the highest degree
      of homology with other enzymes of the DGAT2 family and contains a sequence HPHG
      that is conserved in all family members. Mutagenesis of this sequence in DGAT2
      demonstrated that it is required for full enzymatic function. Additionally, a
      neutral lipid-binding domain that is located in the putative first transmembrane
      domain was also required for full enzymatic function. Our findings provide the
      first insights into the topography and molecular aspects of DGAT2 and related
      enzymes.

PMID- 17035228
TI  - The human sef-a isoform utilizes different mechanisms to regulate receptor
      tyrosine kinase signaling pathways and subsequent cell fate.
AB  - Negative feedback is among the key mechanisms for regulating receptor tyrosine
      kinase (RTK) signaling. Human Sef, a recently identified inhibitor of RTK
      signaling, encodes different isoforms, including a membrane spanning (hSef-a) and
      a cytosolic (hSef-b) isoform. Previously, we reported that hSef-b inhibited
      fibroblast proliferation and prevented the activation of mitogen-activated
      protein kinase (MAPK), without affecting protein kinase B/Akt or p38 MAPK.
      Conflicting results were reported concerning hSef-a inhibition of MAPK
      activation, and the effect of hSef-a on other RTK-induced signaling pathways is
      unknown. Here we show that, in fibroblasts, similar to hSef-b, ectopic expression
      of hSef-a inhibited fibroblast growth factor-induced cell proliferation. Unlike
      hSef-b, however, the growth arrest was mediated via a MAPK-independent mechanism,
      and was accompanied by elevated p38 MAPK phosphorylation and inhibition of
      protein kinase B/Akt. In addition, hSef-a, but not hSef-b, mediated apoptosis in
      fibroblast growth factor-stimulated cells. Chemical inhibitor of p38 MAPK
      abrogated the effect of hSef-a on apoptosis. In epithelial cells, ectopic
      expression of hSef-a inhibited the activation of MAPK, whereas down-regulation of
      endogenous hSef-a significantly increased MAPK activation and accelerated growth
      factor-dependent cell proliferation. These results indicate that hSef-a is a
      multifunctional negative modulator of RTK signaling and clearly demonstrate that
      hSef-a can inhibit the activation of MAPK, although in a cell type-specific
      manner. Moreover, the differences between the activities of hSef-a and hSef-b
      suggest that hSef isoforms can control signal specificity and subsequent cell
      fate by utilizing different mechanisms to modulate RTK signaling.

PMID- 17035229
TI  - Small C-terminal domain phosphatases dephosphorylate the regulatory linker
      regions of Smad2 and Smad3 to enhance transforming growth factor-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) controls a diverse set of cellular
      processes, and its canonical signaling is mediated via TGF-beta-induced
      phosphorylation of receptor-activated Smads (2 and 3) at the C-terminal SXS
      motif. We recently discovered that PPM1A can dephosphorylate Smad2/3 at the C
      terminal SXS motif, implicating a critical role for phosphatases in regulating
      TGF-beta signaling. Smad2/3 activity is also regulated by phosphorylation in the
      linker region (and N terminus) by a variety of intracellular kinases, making it a
      critical platform for cross-talk between TGF-beta and other signaling pathways.
      Using a functional genomic approach, we identified the small C-terminal domain
      phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in
      the linker and N terminus. A catalytically inactive SCP1 mutant (dnSCP1) had no
      effect on Smad2/3 phosphorylation in vitro or in vivo. Of the other FCP/SCP
      family members SCP2 and SCP3, but not FCP1, could also dephosphorylate Smad2/3 in
      the linker/N terminus. Depletion of SCP1/2/3 enhanced Smad2/3 linker
      phosphorylation. SCP1 increased TGF-beta-induced transcriptional activity in
      agreement with the idea that phosphorylation in the Smad2/3 linker must be
      removed for a full transcriptional response. SCP1 overexpression also counteracts
      the inhibitory effect of epidermal growth factor on TGF-beta-induced p15
      expression. Taken together, this work identifies the first example of a Smad2/3
      linker phosphatase(s) and reveals an important new substrate for SCPs.

PMID- 17035230
TI  - Autocrine and juxtacrine effects of amphiregulin on the proliferative, invasive,
      and migratory properties of normal and neoplastic human mammary epithelial cells.
AB  - Amphiregulin (AR) autocrine loops have been associated with several types of
      cancer. We demonstrate that SUM149 breast cancer cells have a self-sustaining AR
      autocrine loop. SUM149 cells are epidermal growth factor (EGF)-independent for
      growth, and they overexpress AR mRNA, AR membrane precursor protein, and secreted
      AR relative to the EGF-dependent human mammary epithelial cell line MCF10A.
      MCF10A cells made to overexpress AR (MCF10A AR) are also EGF-independent for
      growth. Treatment with the pan-ErbB inhibitor CI1033 and the anti-EGF receptor
      (EGFR) antibody C225 demonstrated that ligand-mediated activation of EGFR is
      required for SUM149 cell proliferation. AR-neutralizing antibody significantly
      reduced both SUM149 EGFR activity and cell proliferation, confirming that an AR
      autocrine loop is required for mitogenesis in SUM149 cells. EGFR tyrosine
      phosphorylation was dramatically decreased in both SUM149 and MCF10A AR cells
      after inhibition of AR cleavage with the broad spectrum metalloprotease inhibitor
      GM6001, indicating that an AR autocrine loop is strictly dependent on AR cleavage
      in culture. However, a juxtacrine assay where fixed SUM149 cells and MCF10A AR
      cells were overlaid on top of EGF-deprived MCF10A cells showed that the AR
      membrane precursor can activate EGFR. SUM149 cells, MCF10A AR cells, and MCF10A
      cells growing in exogenous AR were all considerably more invasive and motile than
      MCF10A cells grown in EGF. Moreover, AR up-regulates a number of genes involved
      in cell motility and invasion in MCF10A cells, suggesting that an AR autocrine
      loop contributes to the aggressive breast cancer phenotype.

PMID- 17035231
TI  - RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint.
AB  - Upon DNA damage, replication is inhibited by the S-phase checkpoint. ATR (ataxia
      telangiectasia mutated- and Rad3-related) is specifically involved in the
      inhibition of replicon initiation when cells are treated with DNA damage-inducing
      agents that stall replication forks, but the mechanism by which it acts to
      prevent replication is not yet fully understood. We observed that RPA2 is
      phosphorylated on chromatin in an ATR-dependent manner when replication forks are
      stalled. Mutation of the ATR-dependent phosphorylation sites in RPA2 leads to a
      defect in the down-regulation of DNA synthesis following treatment with UV
      radiation, although ATR activation is not affected. Threonine 21 and serine 33,
      two residues among several phosphorylation sites in the amino terminus of RPA2,
      are specifically required for the UV-induced, ATR-mediated inhibition of DNA
      replication. RPA2 mutant alleles containing phospho-mimetic mutations at ATR
      dependent phosphorylation sites have an impaired ability to associate with
      replication centers, indicating that ATR phosphorylation of RPA2 directly affects
      the replication function of RPA. Our studies suggest that in response to UV
      induced DNA damage, ATR rapidly phosphorylates RPA2, disrupting its association
      with replication centers in the S-phase and contributing to the inhibition of DNA
      replication.

PMID- 17035232
TI  - Gastrointestinal hormones cause rapid c-Met receptor down-regulation by a novel
      mechanism involving clathrin-mediated endocytosis and a lysosome-dependent
      mechanism.
AB  - The activated c-Met receptor has potent effects on normal tissues and tumors. c
      Met levels are regulated by hepatocyte growth factor (HGF); however, it is
      unknown if they can be regulated by gastrointestinal (GI) hormones. c-Met is
      found in many GI tissues/tumors that possess GI hormone receptors. We studied the
      effect of GI hormones on c-Met in rat pancreatic acini, which possess both
      receptors. CCK-8, carbachol, and bombesin, but not VIP/secretin, decreased c-Met.
      CCK-8 caused rapid and potent c-Met down-regulation and abolished HGF-induced c
      Met and Gab1 tyrosine phosphorylation, while stimulating c-Met serine
      phosphorylation. The effect of cholecystokinin (CCK) was also seen in intact
      acini using immunofluorescence, in a biotinylated fraction representing membrane
      proteins, in single acinar cells, in Panc-1 tumor cells, and in vivo in rats
      injected with CCK. CCK-8 did not decrease cell viability or overall
      responsiveness. GF109203X, thapsigargin, or their combination partially reversed
      the effect of CCK-8. In contrast to HGF-induced c-Met down-regulation, the effect
      of CCK was decreased by a lysosome inhibitor (concanamycin) but not the
      proteasome inhibitor lactacystin. Inhibitors of clathrin-mediated endocytosis
      blocked the effect of CCK. HGF but not CCK-8 caused c-Met ubiquitination. These
      results show CCK and other GI hormones can cause rapid c-Met down-regulation,
      which occurs by a novel mechanism. These results could be important for c-Met
      regulation in normal as well as in neoplastic tissue in the GI tract.

PMID- 17035233
TI  - Suppressing Wnt signaling by the hedgehog pathway through sFRP-1.
AB  - The hedgehog (Hh) signaling pathway is essential for embryonic development and
      carcinogenesis. Activation of Hh signaling has been identified in several types
      of gastrointestinal cancers, including esophageal, gastric, pancreatic, and liver
      cancers. Several recent studies suggest that Hh signaling activation can inhibit
      Wnt signaling. However, the molecular basis underlying this inhibition remains
      unclear. As transcription factors in the Hh signaling pathway, Gli molecules
      transform cells in culture, and their expression are associated with cancer
      development. Here we report that expression of a secreted frizzled-related
      protein-sFRP-1 in mouse embryonic fibroblasts is dependent on Gli1 and Gli2. In
      human gastric cancer cells, inhibition of Hh signaling reduces the level of sFRP
      1 transcript, whereas ectopic expression of Gli1 increases the level of sFRP-1
      transcript. Results from chromatin immunoprecipitation indicate that Gli1 is
      involved in transcriptional regulation of sFRP-1. In 293 cells with Gli1
      expression, Wnt-1-mediated beta-catenin accumulation in the cytosol and DKK1
      expression are all abrogated, which can be reversed by inhibiting sFRP-1
      expression. Furthermore, while SIIA cells do not respond to Wnt-1-conditioned
      medium, inhibition of Hh signaling by smoothened (SMO) antagonist KAAD
      cyclopamine (keto-N-aminoethylaminocaproyldihydrocinnamoylcyclopamine) leads to
      Wnt1-mediated beta-catenin accumulation in the cytosol. These data indicate that
      sFRP-1, a target gene of the hedgehog pathway, is involved in cross-talk between
      the hedgehog pathway and the Wnt pathway.

PMID- 17035234
TI  - Physical and functional interaction of the p14ARF tumor suppressor with
      ribosomes.
AB  - Alterations in the p14(ARF) tumor suppressor are frequent in many human cancers
      and are associated with susceptibility to melanoma, pancreatic cancer, and
      nervous system tumors. In addition to its p53-regulatory functions, p14(ARF) has
      been shown to influence ribosome biogenesis and to regulate the endoribonuclease
      B23, but there remains considerable controversy about its nucleolar role. We
      sought to clarify the activities of p14(ARF) by studying its interaction with
      ribosomes. We show that p14(ARF) and B23 interact within the nucleolar 60 S
      preribosomal particle and that this interaction does not require rRNA. In
      contrast to previous reports, we found that expression of p14(ARF) does not
      significantly alter ribosome biogenesis but inhibits polysome formation and
      protein translation in vivo. These results suggest a ribosome-dependent p14(ARF)
      pathway that regulates cell growth and thus complements p53-dependent p14(ARF)
      functions.

PMID- 17035235
TI  - Determinants of RING-E2 fidelity for Hrd1p, a membrane-anchored ubiquitin ligase.
AB  - A critical aspect of E3 ubiquitin ligase function is the selection of a
      particular E2 ubiquitin-conjugating enzyme to accomplish ubiquitination of a
      substrate. We examined the requirements for correct E2-E3 specificity in the RING
      H2 ubiquitin ligase Hrd1p, an ER-localized protein known to use primarily Ubc7p
      for its function. Versions of Hrd1p containing the RING motif from homologous E3s
      were unable to carry out Hrd1p function, revealing a requirement for the specific
      Hrd1p RING motif in vivo. An in vitro assay revealed that these RING motifs were
      sufficient to function as ubiquitin ligases, but that they did not display the E2
      specificity predicted from in vivo results. We further refined the in vitro assay
      of Hrd1p function by demanding not only ubiquitin ligase activity, but also
      specific activity that recapitulated both the E2 specificity and RING selectivity
      observed in vivo. Doing so revealed that correct E2 engagement by Hrd1p required
      the presence of portions of the Hrd1p soluble cytoplasmic domain outside the RING
      motif, the placement of the Hrd1p ubiquitin ligase in the ER membrane, and
      presentation of Ubc7p in the cytosolic context. We confirmed that these
      conditions supported the ubiquitination of Hrd1p itself, and the transfer of
      ubiquitin to the prototype substrate Hmg2p-GFP, validating Hrd1p self
      ubiquitination as a viable assay of ligase function.

PMID- 17035236
TI  - Post-meiotic shifts in HSPA2/HSP70.2 chaperone activity during mouse
      spermatogenesis.
AB  - HSPA2 (formerly HSP70.2) is a testis-specific member of the HSP70 family known to
      play a critical role in the completion of meiosis during male germ cell
      differentiation. Although abundantly present in post-meiotic cells, its function
      during spermiogenesis remained obscure. Here, using a global proteomic approach
      to identify genome-organizing proteins in condensing spermatids, we discovered an
      unexpected role for HSPA2, which acquires new functions and becomes tightly
      associated with major spermatid DNA-packaging proteins, transition proteins 1 and
      2. Hence, HSPA2 is identified here as the first transition protein chaperone, and
      these data shed a new light on the yet totally unknown process of genome
      condensing structure assembly in spermatids.

PMID- 17035237
TI  - CD4 and CCR5 constitutively interact at the plasma membrane of living cells: a
      confocal fluorescence resonance energy transfer-based approach.
AB  - Human immunodeficiency virus entry into target cells requires sequential
      interactions of the viral glycoprotein envelope gp120 with CD4 and chemokine
      receptors CCR5 or CXCR4. CD4 interaction with the chemokine receptor is suggested
      to play a critical role in this process but to what extent such a mechanism takes
      place at the surface of target cells remains elusive. To address this issue, we
      used a confocal microspectrofluorimetric approach to monitor fluorescence
      resonance energy transfer at the cell plasma membrane between enhanced blue and
      green fluorescent proteins fused to CD4 and CCR5 receptors. We developed an
      efficient fluorescence resonance energy transfer analysis from experiments
      carried out on individual cells, revealing that receptors constitutively interact
      at the plasma membrane. Binding of R5-tropic HIV gp120 stabilizes these
      associations thus highlighting that ternary complexes between CD4, gp120, and
      CCR5 occur before the fusion process starts. Furthermore, the ability of CD4
      truncated mutants and CCR5 ligands to prevent association of CD4 with CCR5
      reveals that this interaction notably engages extracellular parts of receptors.
      Finally, we provide evidence that this interaction takes place outside raft
      domains of the plasma membrane.

PMID- 17035238
TI  - Photon flux density-dependent gene expression in Synechocystis sp. PCC 6803 is
      regulated by a small, redox-responsive, LuxR-type regulator.
AB  - The expression of many cyanobacterial genes is regulated by the redox state of
      the photosynthetic electron transport chain. However, factors involved in this
      regulation have not been identified. In this study, we demonstrate that a small
      LuxR-type regulator in Synechocystis sp. PCC 6803, PedR (Ssl0564), senses the
      activity of photosynthetic electron transport to achieve the photon flux density
      dependent transcriptional regulation. PedR is constitutively expressed in
      Synechocystis cells and exists as a dimer bridged by intermolecular disulfide
      bond(s). It activates the expression of chlL, chlN, chlB, and slr1957 and
      represses that of ndhD2, rpe, and the pedR (ssl0564)-sll0296 operon under
      conditions where the activity of photosynthetic electron transport is low. When
      the supply of reducing equivalents from photosynthetic electron transport chain
      increases upon the elevation of photon flux density, PedR is inactivated through
      its conformational change within 5 min. This mechanism enables transient
      induction or repression of the target genes in response to sudden changes in
      light environment. The fact that orthologs of PedR are conserved among all the
      cyanobacterial genomes sequenced so far indicates that this type of
      transcriptional regulation is essential for cyanobacteria to acclimate to
      changing environments.

PMID- 17035239
TI  - Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic
      domain conformation of the ubiquitin-specific protease 8 (USP8).
AB  - Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated
      targets such as epidermal growth factor receptors and is involved in clathrin
      mediated internalization. In 1182 residues, USP8 contains multiple domains,
      including coiled-coil, rhodanese, and catalytic domains. We report the first high
      resolution crystal structures of these domains and discuss their implications for
      USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is
      composed of two five-helix bundles, where the first helices are swapped, and
      carboxyl-terminal helices are extended in an antiparallel fashion. The structure
      of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals
      the canonical rhodanese fold but with a distorted primordial active site. The
      USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a
      conserved peptide loop of the rhodanese domain. A consensus sequence of this loop
      is found in other NRDP1 targets, suggesting a common mode of interaction. The
      structure of the carboxyl-terminal catalytic domain of USP8 exhibits the
      conserved tripartite architecture but shows unique traits. Notably, the active
      site, including the ubiquitin binding pocket, is in a closed conformation,
      incompatible with substrate binding. The presence of a zinc ribbon subdomain near
      the ubiquitin binding site further suggests a polyubiquitin-specific binding site
      and a mechanism for substrate induced conformational changes.

PMID- 17035240
TI  - Indirect recognition in sequence-specific DNA binding by Escherichia coli
      integration host factor: the role of DNA deformation energy.
AB  - Integration host factor (IHF) is a bacterial histone-like protein whose primary
      biological role is to condense the bacterial nucleoid and to constrain DNA
      supercoils. It does so by binding in a sequence-independent manner throughout the
      genome. However, unlike other structurally related bacterial histone-like
      proteins, IHF has evolved a sequence-dependent, high affinity DNA-binding motif.
      The high affinity binding sites are important for the regulation of a wide range
      of cellular processes. A remarkable feature of IHF is that it employs an indirect
      readout mechanism to bind and wrap DNA at both the nonspecific and high affinity
      (sequence-dependent) DNA sites. In this study we assessed the contributions of
      pre-formed and protein-induced DNA conformations to the energetics of IHF
      binding. Binding energies determined experimentally were compared with energies
      predicted for the IHF-induced deformation of the DNA helix (DNA deformation
      energy) in the IHF-DNA complex. Combinatorial sets of de novo DNA sequences were
      designed to systematically evaluate the influence of sequence-dependent
      structural characteristics of the conserved IHF recognition elements of the
      consensus DNA sequence. We show that IHF recognizes pre-formed conformational
      characteristics of the consensus DNA sequence at high affinity sites, whereas at
      all other sites relative affinity is determined by the deformational energy
      required for nearest-neighbor base pairs to adopt the DNA structure of the bound
      DNA-IHF complex.

PMID- 17035241
TI  - Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity
      to store depletion-induced apoptosis in neural cells.
AB  - An increase in the cytoplasmic-free Ca(2+) concentration mediates cellular
      responses to environmental signals that influence a range of processes, including
      gene expression, motility, secretion of hormones and neurotransmitters, changes
      in energy metabolism, and apoptosis. Mitochondria play important roles in
      cellular Ca(2+) homeostasis and signaling, but the roles of specific
      mitochondrial proteins in these processes are unknown. Uncoupling proteins (UCPs)
      are a family of proteins located in the inner mitochondrial membrane that can
      dissociate oxidative phosphorylation from respiration, thereby promoting heat
      production and decreasing oxyradical production. Here we show that UCP4, a
      neuronal UCP, influences store-operated Ca(2+) entry, a process in which
      depletion of endoplasmic reticulum Ca(2+) stores triggers Ca(2+) influx through
      plasma membrane "store-operated" channels. PC12 neural cells expressing human
      UCP4 exhibit reduced Ca(2+) entry in response to thapsigargin-induced endoplasmic
      reticulum Ca(2+) store depletion. The elevations of cytoplasmic and
      intramitochondrial Ca(2+) concentrations and mitochondrial oxidative stress
      induced by thapsigargin were attenuated in cells expressing UCP4. The
      stabilization of Ca(2+) homeostasis and preservation of mitochondrial function by
      UCP4 was correlated with reduced mitochondrial reactive oxygen species
      generation, oxidative stress, and Gadd153 up-regulation and increased resistance
      of the cells to death. Reduced Ca(2+)-dependent cytosolic phospholipase A2
      activation and oxidative metabolism of arachidonic acid also contributed to the
      stabilization of mitochondrial function in cells expressing human UCP4. These
      findings demonstrate that UCP4 can regulate cellular Ca(2+) homeostasis,
      suggesting that UCPs may play roles in modulating Ca(2+) signaling in
      physiological and pathological conditions.

PMID- 17035242
TI  - Human Daxx-mediated repression of human cytomegalovirus gene expression
      correlates with a repressive chromatin structure around the major immediate early
      promoter.
AB  - Upon herpesvirus infection, viral DNA becomes associated with nuclear structures
      known as nuclear domain 10 (ND10). The role of ND10 during herpesvirus infection
      has long been contentious; data arguing for a role for ND10 in repression of
      infection have been countered by other data showing little effect of ND10 on
      virus infection. Here we show that knockdown of human Daxx (hDaxx) expression, an
      important component of ND10, prior to infection with human cytomegalovirus
      resulted in increased levels of viral immediate early RNA and protein expression
      and that this correlated with an increased association of the major immediate
      early promoter with markers of transcriptionally active chromatin. Conversely, we
      also show that stable overexpression of hDaxx renders cells refractory to
      cytomegalovirus immediate early gene expression. Intriguingly, this hDaxx
      mediated repression appears to be restricted to cells stably overexpressing hDaxx
      and is not recapitulated in transient transfection assays. Finally, hDaxx
      mediated repression of cytomegalovirus major immediate early gene expression was
      overcome by infecting at higher virus titers, suggesting that an incoming viral
      structural protein or viral DNA is responsible for overcoming the repression of
      viral gene expression in hDaxx superexpressing cells. These data suggest that
      hDaxx in ND10 functions at the site of cytomegalovirus genome deposition to
      repress transcription of incoming viral genomes and that this repression is
      mediated by a direct and immediate effect of hDaxx on chromatin modification
      around the viral major immediate early promoter.

PMID- 17035243
TI  - Act1 adaptor protein is an immediate and essential signaling component of
      interleukin-17 receptor.
AB  - Interleukin (IL)-17, the founding member of the IL-17 cytokine family, is the
      hallmark of a novel subset of CD4+ T cells that is regulated by TGFbeta, IL-6,
      and IL-23. IL-17 plays an important role in promoting tissue inflammation in host
      defense against infection and in autoimmune diseases. Although IL-17 has been
      reported to regulate the expression of proinflammatory cytokines, chemokines, and
      matrix metalloproteinases, the signaling mechanism of IL-17 receptor has not been
      understood. An earlier study found that IL-17 activates NF-kappaB and MAPK
      pathways and requires TRAF6 to induce IL-6. However, it is unknown what
      molecule(s) directly associates with IL-17 receptor to initiate the signaling. We
      demonstrate here that IL-17 receptor family shares sequence homology in their
      intracellular region with Toll-IL-1 receptor (TIR) domains and with Act1, a novel
      adaptor previously reported as an NF-kappaB activator. MyD88 and IRAK4,
      downstream signaling components of TIR, are not required for IL-17 signaling. On
      the other hand, Act1 and IL-17 receptor directly associate likely via homotypic
      interaction. Deficiency of Act1 in fibroblast abrogates IL-17-induced cytokine
      and chemokine expression, as well as the induction of C/EBPbeta, C/EBPdelta, and
      IkappaBzeta. Also, absence of Act1 results in a selective defect in IL-17-induced
      activation of NF-kappaB pathway. These results thus indicate Act1 as a membrane
      proximal adaptor of IL-17 receptor with an essential role in induction of
      inflammatory genes. Our study not only for the first time reveals an immediate
      signaling mechanism downstream of an IL-17 family receptor but also has
      implications in therapeutic treatment of various immune diseases.

PMID- 17035244
TI  - Cross-linking between helices within subunit a of Escherichia coli ATP synthase
      defines the transmembrane packing of a four-helix bundle.
AB  - Subunit a of F(1)F(0) ATP synthase is required in the H(+) transport driven
      rotation of the c-ring of F(0), the rotation of which is coupled to ATP synthesis
      in F(1). The three-dimensional structure of subunit a is unknown. In this study,
      Cys substitutions were introduced into two different transmembrane helices (TMHs)
      of subunit a, and the proximity of the thiol side chains was tested via attempted
      oxidative cross-linking to form the disulfide bond. Pairs of Cys substitutions
      were made in TMHs 2/3, 2/4, 2/5, 3/4, 3/5, and 4/5. Cu(+2)-catalyzed oxidation
      led to cross-link formation between Cys pairs L120C(TMH2) and S144C(TMH3),
      L120C(TMH2) and G218C(TMH4), L120C(TMH2) and H245C(TMH5), L120C(TMH2) and
      I246C(TMH5), N148C(TMH3) and E219C(TMH4), N148C(TMH3) and H245C(TMH5), and
      G218C(TMH4) and I248C(TMH5). Iodine, but not Cu(+2), was found to catalyze cross
      link formation between D119C(TMH2) and G218C(TMH4). The results suggest that TMHs
      2, 3, 4, and 5 form a four-helix bundle with one set of key functional residues
      in TMH4 (Ser-206, Arg-210, and Asn-214) located at the periphery facing subunit
      c. Other key residues in TMHs 2, 4, and 5, which were concluded previously to
      compose a possible aqueous access pathway from the periplasm, were found to
      locate to the inside of the four-helix bundle.

PMID- 17035245
TI  - Brief interventions for at-risk drinking: patient outcomes and cost-effectiveness
      in managed care organizations.
AB  - AIMS: Evaluate effectiveness and costs of brief interventions for patients
      screening positive for at-risk drinking in managed health care organizations
      (MCOs). METHODS: A pre-post, quasi-experimental, multi-site evaluation conducted
      at 15 clinic sites within five MCO settings. At-risk drinkers (N = 1329) received
      either: (i) brief intervention delivered by licensed practitioners; or (ii) brief
      intervention delivered by mid-level professional specialists (nurses); or (iii)
      usual care (comparison condition). Clinics were randomly assigned to three study
      conditions. Data were collected on the cost of screening and brief intervention.
      Follow-up interviews were conducted at 3 and 12 months. RESULTS: Participants in
      all three study conditions were drinking significantly less at 3-month follow-up,
      but the decline was significantly greater in the two intervention groups than in
      the control group. There were no significant differences between the two
      intervention conditions. Of the patients in the intervention conditions 60%
      reduced their alcohol consumption by > or =1 drink per week, compared with 53% of
      those in the control condition. No differences were found on a measure of the
      quality of life. Differential reductions in weekly alcohol consumption between
      intervention and control groups were significant at 12-month follow-up. Average
      incremental costs of the interventions were 4.16 US dollar per patient using
      licensed practitioners and 2.82 US dollar using mid-level specialists.
      CONCLUSION: Alcohol screening and brief intervention when implemented in managed
      care organizations produces modest, statistically significant reductions in at
      risk drinking. Interventions delivered to a common protocol by mid-level
      specialists are as effective as those delivered by licensed practitioners at
      about two-thirds the cost.

PMID- 17035246
TI  - Identification of susceptibility loci for cervical carcinoma by genome scan of
      affected sib-pairs.
AB  - Cervical cancer is caused by a combination of environmental and genetic risk
      factors. Infection by oncogenic types of human papillomavirus is recognized as
      the major environmental risk factor and epidemiological studies indicate that
      host genetic factors predispose to disease development. A number of genetic
      susceptibility factors have been proposed, but with exception of the human
      leukocyte antigen CHLA, class II, have not shown consistent results among
      studies. We have performed the first genomewide linkage scan using 278 affected
      sib-pairs to identify loci involved in susceptibility to cervical cancer. A two
      step qualitative non-parametric linkage analysis using 387 microsatellites with
      an average spacing of 10.5 cM revealed excess allelic sharing at nine regions on
      eight chromosomes. These regions were further analysed with 125 markers to
      increase the map density to 1.28 cM. Nominal significant linkage was found for
      three of the nine loci [9q32 (maximum lod-score, MLS) =1.95, P<0.002), 12q24
      (MLS=1.25, P<0.015) and 16q24 (MLS=1.35, P<0.012)]. These three regions have
      previously been connected to human cancers that share characteristics with
      cervical carcinoma, such as esophageal cancer and Hodgkin's lymphoma. A number of
      candidate genes involved in defence against viral infections, immune response and
      tumour suppression are found in these regions. One such gene is the thymic
      stromal co-transporter (TSCOT). Analyses of TSCOT single nucleotide polymorphisms
      further strengthen the linkage to this region (MLS=2.40, P<0.001). We propose
      that the 9q32 region contains susceptibility locus for cervical cancer and that
      TSCOT is a candidate gene potentially involved in the genetic predisposition to
      this disease.

PMID- 17035247
TI  - Overrepresentation of rare variants in a specific ethnic group may confuse
      interpretation of association analyses.
AB  - Rare sequence variants may be important in understanding the biology of common
      diseases, but clearly establishing their association with disease is often
      difficult. Association studies of such variants are becoming increasingly common
      as large-scale sequence analysis of candidate genes has become feasible. A recent
      report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette
      Syndrome (TS). The statistical evidence for this suggestion came from association
      analyses of a rare 3'-UTR variant, var321, which was observed in two patients but
      not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515
      Ashkenazi individuals (TS probands and their parents) and observed var321 in five
      independent Ashkenazi parents, two of whom did not transmit this variant to their
      affected child. Furthermore, we identified var321 in one subject from an
      Ashkenazi control sample. Our findings do not support the previously reported
      association and suggest that var321 is overrepresented among Ashkenazi Jews
      compared with other populations of European origin. The results further suggest
      that overrepresentation of rare variants in a specific ethnic group may
      complicate the interpretation of association analyses of such variants,
      highlighting the particular importance of precisely matching case and control
      populations for association analyses of rare variants.

PMID- 17035248
TI  - DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite
      outgrowth, is modulated by genetic variations of DISC1.
AB  - Disrupted-In-Schizophrenia-1 (DISC1) is a unique susceptibility gene for major
      mental conditions, because of the segregation of its genetic variant with
      hereditary psychosis in a Scottish pedigree. Genetic association studies
      reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar
      disorder in several ethnic groups. The DISC1 protein is multifunctional, and a
      pool of DISC1 in the dynein motor complex is required for neurite outgrowth in
      PC12 cells as well as proper neuronal migration and dendritic arborization in the
      developing cerebral cortex in vivo. Here, we show that a specific interaction
      between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for
      neurite outgrowth in differentiating PC12 cells. Among several components of the
      dynein motor complex, DISC1 and NDEL1 are selectively upregulated during neurite
      outgrowth upon differentiation in PC12 cells. The NDEL1 binding site of DISC1 was
      narrowed down to a small portion of exon 13, corresponding to amino acids 802-835
      of DISC1. We demonstrate that genetic variants of DISC1, proximal to the NDEL1
      binding site, affect the interaction between DISC1 and NDEL1.

PMID- 17035249
TI  - A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse.
AB  - Otitis media (OM), inflammation of the middle ear, is the most common cause of
      hearing impairment and surgery in children. Recurrent and chronic forms of OM are
      known to have a strong genetic component, but nothing is known of the underlying
      genes involved in the human population. We have previously identified a novel
      semi-dominant mouse mutant, Jeff, in which the heterozygotes develop chronic
      suppurative OM (Hardisty, R.E., Erven, A., Logan, K., Morse, S., Guionaud, S.,
      Sancho-Oliver, S., Hunter, A.J., Brown, S.D. and Steel, K.P. (2003) The deaf
      mouse mutant Jeff (Jf) is a single gene model of otitis media. J. Assoc. Res.
      Otolaryngol., 4, 130-138.) and represent a model for chronic forms of OM in
      humans. We demonstrate here that Jeff carries a mutation in an F-box gene,
      Fbxo11. Fbxo11 is expressed in epithelial cells of the middle ears from late
      embryonic stages through to day 13 of postnatal life. In contrast to Jeff
      heterozygotes, Jeff homozygotes show cleft palate, facial clefting and perinatal
      lethality. We have also isolated and characterized an additional hypomorphic
      mutant allele, Mutt. Mutt heterozygotes do not develop OM but Mutt homozygotes
      also show facial clefting and cleft palate abnormalities. FBXO11 is one of the
      first molecules to be identified, contributing to the genetic aetiology of OM. In
      addition, the recessive effects of mutant alleles of Fbxo11 identify the gene as
      an important candidate for cleft palate studies in the human population.

PMID- 17035251
TI  - Arterial stiffness: reflections on the arterial pulse.

PMID- 17035250
TI  - Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive
      cutis laxa.
AB  - To elucidate the molecular mechanisms of impaired elastic fiber formation in
      recessive cutis laxa, we have investigated two disease-causing missense
      substitutions in fibulin-5, C217R and S227P. Pulse-chase immunoprecipitation
      experiments indicated that S227P mutant fibulin-5 was synthesized and secreted by
      skin fibroblasts at a reduced rate when compared with the wild-type protein. Both
      mutants failed to be incorporated into elastic fibers by transfected rat lung
      fibroblasts. Purified recombinant fibulin-5 with either mutation showed reduced
      affinity for tropoelastin in solid-phase binding assays. Furthermore, S227P
      mutant fibulin-5 also showed impaired association with fibrillin-1 microfibrils.
      The same mutation triggered an endoplasmic reticulum (ER) stress response, as
      indicated by the strong co-localization of this mutant protein with folding
      chaperones in the ER, including calreticulin, immunoglobulin-binding protein and
      protein disulfide isomerase, and by increased rates of apoptosis in patient
      fibroblasts. Histological analysis of skin sections from a cutis laxa patient
      with a homozygous S227P mutation showed a lack of fibulin-5 in the extracellular
      matrix and a concomitant disorganization of dermal elastic fibers. By electron
      microscopy, elastic fibers in the skin of this patient showed a failure of
      elastin globules to fuse into a continuous elastic fiber core. We conclude that
      recessive cutis laxa mutations in fibulin-5 result in misfolding, decreased
      secretion and a reduced interaction with elastin and fibrillin-1 leading to
      impaired elastic fiber development. These findings support the hypothesis that
      fibulin-5 is necessary for elastic fiber formation by facilitating the deposition
      of elastin onto a microfibrillar scaffold via direct molecular interactions.

PMID- 17035252
TI  - Assessment of coronary artery stent restenosis by 64-slice multi-detector
      computed tomography.
AB  - AIMS: We investigated the feasibility of assessing coronary artery stent
      restenosis using a new generation 64-slice multi-detector computed tomography
      scanner (MDCT) in comparison to conventional quantitative angiography. METHODS
      AND RESULTS: MDCT was performed in 64 consecutive patients (mean age 58+/-10
      years) with previously implanted coronary artery stents (102 stented lesions:
      mean stent diameter 3.17+/-0.38 mm). Each stent was classified as 'evaluable' or
      'unevaluable', and in evaluable stents, the presence of in-stent restenosis
      (diameter reduction >50%) was determined visually. Results were verified against
      invasive, quantitative coronary angiography. Fifty-nine stented lesions (58%)
      were classified as evaluable in MDCT. The mean diameter of evaluable stents was
      3.28+/-0.40 mm, whereas the mean diameter of non-evaluable stents was 3.03+/-0.31
      mm (P=0.0002). Overall, six of 12 in-stent restenoses were correctly detected by
      MDCT [50% sensitivity (confidence interval 22-77%)] and in 51 of 90 lesions, in
      stent restenosis was correctly ruled out [57% specificity (46-67%)]. In evaluable
      stents, six of seven in-stent restenoses were correctly detected, and the absence
      of in-stent stenosis was correctly identified in 51 of 52 cases [sensitivity 86%
      (42-99%) and specificity 98% (88-100%)]. CONCLUSION: Stent type and diameter
      influence evaluability concerning in-stent restenosis by MDCT. The rate of
      assessable stents is low, but in evaluable stents, accuracy for detection of in
      stent restenosis can be high.

PMID- 17035253
TI  - Analysis of myocardial deformation based on ultrasonic pixel tracking to
      determine transmurality in chronic myocardial infarction.
AB  - AIMS: Pixel tracking-derived myocardial deformation imaging is a new
      echocardiographic modality which allows quantitative analysis of segmental
      myocardial function on the basis of tracking of natural acoustic markers in 2D
      echocardiography. This study evaluated whether myocardial deformation parameters
      calculated from 2D echocardiography allow assessment of transmurality of
      myocardial infarction as defined by contrast-enhanced cardiac magnetic resonance
      imaging (ceMRI). Methods In 47 patients with ischaemic left ventricular
      dysfunction, transmurality of myocardial infarction was assessed using pixel
      tracking-derived myocardial deformation imaging and ceMRI. For each left
      ventricular segment in a 16-segment model, peak systolic radial strain,
      circumferential strain, radial strain rate, and circumferential strain rate were
      calculated from parasternal 2D echocardiographic views using an automatic frame
      by-frame tracking system of natural acoustic echocardiographic markers (EchoPAC,
      GE Ultrasound). Myocardial deformation parameters were related to the segmental
      extent of hyperenhancement by ceMRI. The relative amount of contrast-enhanced
      myocardial tissue per segment was used to define no infarction (0%
      hyperenhancement), non-transmural infarction (1-50% hyperenhancement), or
      transmural infarction (51-100% hyperenhancement). Results Analysis of myocardial
      deformation parameters was possible in 659 segments (88%). Systolic strain and
      strain rate parameters decreased with increasing relative hyperenhancement
      defined by ceMRI. Radial strain was 27.7+/-8.0, 20.5+/-9.7, and 11.6+/-8.5% for
      segments with no infarction (n=422), non-transmural infarction (n=106), and
      transmural infarction (n=131), respectively (P<0.0001). Radial strain allowed
      distinction of non-transmural infarction from transmural infarction with a
      sensitivity of 70.0% and a specificity of 71.2% (cut-off value for radial strain
      16.5%). CONCLUSION: Frame-to-frame tracking of acoustic markers in 2D
      echocardiographic images for the analysis of myocardial deformation allows
      discrimination between different transmurality states of myocardial infarction.

PMID- 17035254
TI  - Traffic and the heart.

PMID- 17035255
TI  - Satisfaction with life, psychosocial health and materialism among Hungarian
      youth.
AB  - Previous research suggests that youth's life satisfaction may be influenced by
      health and certain socioeconomic/sociocultural factors, which may be important in
      a post-socialist country like Hungary. We investigated the relationship between
      youth's life satisfaction, materialism and their psychosocial health in a sample
      of secondary school students (N = 1114) in Hungary. Findings show that youth's
      psychosocial health may play an important role in their levels of life
      satisfaction, particularly depressive and psychosomatic symptoms and health
      behaviors (e.g. diet control and smoking). SES self-assessment and materialistic
      success were positively, while materialistic happiness was negatively related to
      youth's life satisfaction.

PMID- 17035256
TI  - Negative affect as a mediator between body dissatisfaction and extreme weight
      loss and muscle gain behaviors.
AB  - Negative affect has been found to mediate the relationship between body
      dissatisfaction and bulimia. However, it is unknown if this relationship also
      applies to disordered eating, excessive exercise and strategies to increase
      muscle for men or women. The aim of this study was to investigate whether
      negative and positive affect mediate the relationship between body
      dissatisfaction, and these body change strategies. Respondents were 93 men and 97
      women (age range: 18-25 years), who completed measures of body dissatisfaction,
      positive and negative affect and body change strategies to lose weight or
      increase muscles. Body dissatisfaction was associated with strategies to lose
      weight, dietary restraint and bulimia for both genders. Negative affect mediated
      the relationship between dissatisfaction with muscles and strategies to lose
      weight, dietary restraint and bulimia for women only. The results confirm
      previous findings related to the association between negative affect and
      disordered eating for women. They also demonstrate the need to further
      investigate the impact of negative affect on body change strategies, particularly
      among men, and those strategies related to increasing muscles.

PMID- 17035257
TI  - Experiences of anabolic steroid use: in-depth interviews with men and women body
      builders.
AB  - This study was designed to investigate anabolic steroid users' experiences of,
      and motivations for, use. Five men and six women users took part in in-depth
      interviews. Four themes emerged: Steroid Use vs Abuse; Side-effects; Trusted
      Information Sources; and Social Pressure. Many users believed that steroids used
      in moderation were safe. Serious side-effects (liver and kidney damage,
      hypertension) were not significant disincentives. Information from health
      professionals tended to be mistrusted because it was not based on first-hand
      experience of use. Social support, especially from within the body building
      community, was an important motivator. It is concluded that intervention
      programmes need the support of the body building community in order to be
      effective.

PMID- 17035258
TI  - A psychosocial resilience model to account for medical well-being in relation to
      sense of coherence.
AB  - We tested the suggestion that Sense of Coherence (SOC) may enhance medical well
      being by virtue of a favorably balanced profile of psychosocial assets relative
      to liabilities. Results derived from a sample of 81 young adults who responded to
      a battery of inventories supported the Psychosocial Resilience Model. Our
      findings provide preliminary evidence to suggest that a favorable balance between
      psychosocial 'protective' and 'risk' factors may, in part, help explain why
      people with a strong SOC enjoy high levels of medical well-being.

PMID- 17035259
TI  - Attachment, social support and well-being in young and older adults.
AB  - The present study examined the link between attachment, social support and well
      being in young and older adults. The results from multi-group path analyses
      showed significant between-group differences in the links between attachment,
      perceived support and well-being. Anxious attachment and well-being were
      inversely associated and this was stronger for the younger group than it was for
      the older group. Avoidant attachment was negatively related to perceived support
      satisfaction in the older age group only, and perceived support mediated the
      effects of avoidant attachment on mental health and loneliness in the older
      group. Generally, perceived satisfaction with support was more strongly related
      with well-being in older adults. The results point to differential links of
      insecure attachment styles with perceived support in different life-stages and to
      related cognitive, emotional and social processes.

PMID- 17035260
TI  - Adult attachment, reassurance seeking and hypochondriacal concerns in college
      students.
AB  - An individual's attachment style can be conceptualized as a working model for
      interactions with others, developed as result of experiences with childhood
      caregivers. People with hypochondriacal tendencies are preoccupied with thoughts
      of having an illness and constantly seek medical reassurance. We hypothesized
      that students with preoccupied attachment would score highly on a measure of
      hypochondriasis and investigated whether the association would be explained by
      the general tendency to seek reassurance in relationships. A total of 117
      undergraduate students completed questionnaires measuring attachment style;
      negative affectivity; reassurance seeking in relationships and hypochondriasis.
      Participants with preoccupied attachment style (n = 17, 15%) had significantly
      higher hypochondriasis scores than those with other attachment styles.
      Hierarchical multiple regression analysis suggested that the association between
      the preoccupied attachment style and hypochondriasis was explained by the general
      tendency to seek reassurance in relationships, with negative affectivity, a
      dispositional variable, also acting as a significant predictor of
      hypochondriasis.

PMID- 17035261
TI  - Examining exercise dependence symptomatology from a self-determination
      perspective.
AB  - Background Pulling from Self-Determination Theory (SDT; Deci & Ryan, 1985), this
      study examined whether individuals classified as 'nondependent-symptomatic' and
      'nondependent-asymptomatic' for exercise dependence differed in terms of reported
      levels of exercise-related psychological need satisfaction, self-determined
      versus controlling motivation and exercise behavior. In addition, we examined the
      type of motivational regulations predicting exercise behavior among these
      different groups, and their role as mediators between psychological need
      satisfaction and behavioral outcomes. Methods Participants (N = 339) completed
      measures of exercise-specific psychological need satisfaction, motivational
      regulations, exercise behavior and exercise dependence. Results Nondependent
      symptomatic individuals reported higher levels of competence need satisfaction
      and all forms of motivational regulation, compared to nondependent-asymptomatic
      individuals. Introjected regulation approached significance as a positive
      predictor of strenuous exercise behavior for symptomatic individuals. Identified
      regulation was a positive predictor of strenuous exercise, and completely
      mediated the relationship between competence need satisfaction and strenuous
      exercise behavior, for asymptomatic individuals. Conclusions The findings
      reinforce the applicability of SDT to understanding the quantity and quality of
      engagement in exercise.

PMID- 17035262
TI  - Preferring proxy-agency: impact on self-efficacy for exercise.
AB  - We examined: (a) the social-cognitions of those who differ in preferred level of
      proxy-assistance in both proxy-led and independent exercise contexts; and (b) the
      relationships between proxy-agency and reliance. Sixty-five fitness class
      participants completed measures of self-regulatory efficacy, task self-efficacy,
      exercise intentions, proxy-efficacy and perceived reliance. A 2 (exercise
      context) by 2 (preferred assistance) MANOVA revealed significant main effects for
      assistance and context. Also, significant assistance by context interactions was
      found for both efficacies. When facing exercise without a proxy, individuals
      preferring high proxy assistance expressed lower self-regulatory and task self
      efficacy. Finally, proxy- and self-regulatory efficacy were shown to be separate
      predictors of reliance on a proxy. Results support Bandura's theorizing about the
      proxy-led context and its influence on self-regulatory efficacy.

PMID- 17035263
TI  - Adherence to chest physiotherapy in adults with cystic fibrosis.
AB  - Chest physiotherapy (CP) is seen as a cornerstone of Cystic Fibrosis (CF)
      treatment. However, previous studies have suggested that adherence to CP is low.
      This study of adults with CF (N = 563) investigated CP adherence and associated
      factors. Only 29.5 per cent reported undertaking daily CP. Predictors of
      adherence included problems with fitting CP into lifestyle, a perception that CP
      does not help, physical consequences of CP, doing exercises instead and doing CP
      as and when necessary. These variables accounted for 45 per cent of the variance
      in adherence. Content analysis revealed a number of themes related to adherence
      to CP. Future studies should explore the benefits of daily CP and attempt to
      devise simple interventions to maximize adherence to CP.

PMID- 17035264
TI  - Goal processes in relation to goal attainment: predicting health-related quality
      of life in myocardial infarction patients.
AB  - Goal theory suggests that both goal attainment and psychological processes
      concerning goal pursuit can influence a patient's (health-related) quality of
      life (HRQL) (e.g. Carver & Scheier, 1999). In the present longitudinal study, 46
      MI patients completed questionnaires shortly after hospitalization and four
      months later, assessing a health, social and individual goal for the coming year,
      goal conflict, goal self-efficacy, goal attainment and HRQL. The results of a
      multiple regression analysis suggest that both goal conflict and goal self
      efficacy predict goal attainment. Furthermore, goal self-efficacy appeared to be
      an independent predictor of physical and social HRQL. Goal attainment had a
      medium effect on social HRQL, but its effect was mediated by goal conflict and
      goal self-efficacy. A goal theory perspective seems to offer additional insights
      into HRQL after an MI.

PMID- 17035265
TI  - 'Why I won't eat': patient testimony from 15 anorexics concerning the causes of
      their disorder.
AB  - The following article describes the reasons given by 15 anorexic patients for
      their illness. The patients were asked the following question in an open-ended
      interview-'What would you say were the causes of your illness?' In reply detailed
      complex narratives were gathered from which a number of themes could be
      identified. These included unhappiness, control, being in a downward spiral,
      obsession and perfectionism. Most patients, for example explained that they were
      unhappy. To address their unhappiness, they adopted a strategy of control over
      food. Being able to exert this control gave patients a sense of enjoyment and
      pride and enabled them to address their underlying fear that a loss of control
      may be just around the corner. This pride persuaded patients to restrict further
      their food in the hope they would experience even greater enjoyment. Patients
      were thus caught in a dangerous 'spiral' of restriction, weight loss, euphoria
      and further food refusal. This spiralling behaviour resulted in many patients
      describing their illness as an obsession. Several patients equated this
      obsessional behaviour with a perfectionist trait in their personalities. In the
      following article, these themes of unhappiness, control, spiral, obsession and
      perfectionism, are presented, along with the patient testimony on which each
      theme was based.

PMID- 17035267
TI  - Is early age-related macular degeneration related to carotid artery stiffness?
      The Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND/PURPOSE: Atherosclerosis and vascular stiffness have been implicated
      in the pathogenesis of age-related macular degeneration (AMD). The association of
      carotid artery stiffness, a measure of arterial elasticity reflecting early
      atherosclerosis, with early AMD, was examined in this study. METHODS: A
      population-based, cross-sectional study of 9954 middle-aged people (age range 51
      72 years). The presence of AMD signs was determined from fundus photographs
      according to the Wisconsin grading protocol. Carotid arterial stiffness was
      measured from high-resolution ultrasonic echo tracking of the left common carotid
      artery, and was defined as an adjusted arterial diameter change (AADCmu). A
      smaller AADC reflects greater carotid artery stiffness. The associations of pulse
      pressure and carotid artery intima-media thickness (IMT) with early AMD signs
      were also analysed. RESULTS: In the study population, 454 (4.6%) had early AMD.
      The mean (SD) AADC was 403 (127) mu. After adjusting for age, sex, race/centre,
      education, cigarette smoking, fasting glucose, lipid profile and inflammatory
      markers, a smaller AADC was found to be not associated with early AMD (odds ratio
      0.94; 95% confidence interval, 0.71 to 1.25) or its component lesions. Other
      measures of arterial stiffness (pulse pressure) and atherosclerosis (carotid IMT)
      were also not associated with early AMD. CONCLUSIONS: Carotid artery stiffness
      was not associated with signs of early AMD in this middle-aged population. These
      data provide no evidence of a link between age-related elastoid changes and early
      atherosclerotic processes in the carotid arteries and early AMD.

PMID- 17035268
TI  - Viscoelastic shear properties of the fresh porcine lens.
AB  - AIM: To determine the viscoelastic properties of the porcine lens METHODS: Linear
      viscoelastic shear properties of the stroma of four porcine lenses were measured
      within 5 hours post-mortem, using sinusoidal oscillatory shear deformation. The
      elastic shear modulus, viscous shear modulus, dynamic viscosity, damping ratio,
      and phase shift of the lenses were quantified by a controlled-strain, linear
      simple-shear rheometer at frequencies of 10-50 Hz. RESULTS: The mean viscoelastic
      properties and their standard deviations across the frequencies examined were:
      the elastic shear modulus, G' = 6.2+/-4.0 Pa, the viscous shear modulus, G'' =
      19.2+/-2.5 Pa, the dynamic viscosity, eta' = 0.16+/-0.1 Pa x sec, the damping
      ratio zeta = 4.06+/-1.25, and the phase shift, delta = 76 degrees +/- 5.6
      degrees. CONCLUSIONS: The measured viscoelastic shear properties of the porcine
      lens reflect a low dynamic viscosity with a high damping ratio. The porcine lens
      is viscoelastic and is more viscous than elastic. The magnitude of the complex
      shear modulus of the porcine lens, |G*|, is similar to the shear modulus of the
      young human lens. Understanding these viscoelastic properties of the natural lens
      may provide guidance in developing a lens substitute capable of accommodation in
      the post cataract patient.

PMID- 17035269
TI  - Clinical characteristics of Mooren's ulcer in South India.
AB  - AIM: To describe the clinical characteristics at presentation of a large cohort
      of patients with Mooren's ulcer in South India. METHODS: The medical records of
      patients with Mooren's ulcer examined in the cornea clinic at Aravind Eye
      Hospital Madurai, Tamil Nadu, India, over a 10-year period were reviewed in this
      retrospective observational case series. RESULTS: The cohort contained 242 eyes
      of 166 patients. All patients were from South India, and men outnumbered women by
      a ratio of 4.7:1. The median and mean ages at presentation were 65 and 61 years,
      respectively, with a range of 13-95 years. One eye was affected in 90 of 166
      (54%) patients. Visual acuity in the affected eye at presentation ranged from 6/6
      to light perception, and was 6/12 or better in 34 of 242 (14%) eyes, between 6/12
      and 3/60 in 168 (69%) eyes, and worse than 3/60 in 40 (17%) eyes. Partial
      peripheral corneal ulceration was observed in 222 (92%) eyes, complete peripheral
      corneal ulceration was observed in 15 (6%) eyes and total corneal ulceration was
      observed in 5 (2%) eyes. For those 222 eyes with partial peripheral ulceration,
      152 (68%) showed temporal involvement, 129 (58%) showed nasal involvement, 116
      (52%) showed inferior involvement and 30 (14%) showed superior involvement.
      Perforation was observed in 26 (11%) eyes, and was more common in eyes with
      peripheral as compared with total ulceration (p<0.001). Identified risk factors
      in the cohort included evidence of prior corneal surgery (22%), corneal trauma
      (17%) and corneal infection (2%). CONCLUSIONS: Mooren's ulcer is a rare and
      potentially blinding eye condition observed not infrequently in the cornea clinic
      at Aravind Eye Hospital. Men are affected more often than women and may present
      with either unilateral or bilateral disease. Perforation is observed in
      approximately 1 in 10 affected eyes at presentation and occurs most often in the
      setting of peripheral ulceration. The occurrence of prior corneal surgery, trauma
      or infection in nearly one third of patients supports theories of exposure to
      corneal antigen in the pathogenesis of this disorder.

PMID- 17035270
TI  - Value of retinal vein pulsation characteristics in predicting increased optic
      disc excavation.
AB  - BACKGROUND: Retinal vein pulsation is often absent in glaucoma, but can be
      induced by applying a graded ophthalmodynamometric force (ODF) to the eye, which
      is elevated in glaucoma. AIM: To assess whether ODF has a predictive value in
      determining glaucoma progression. METHODS: 75 patients with glaucoma and
      suspected glaucoma were examined prospectively in 1996, and then re-examined at a
      mean of 82 months later. All subjects had intraocular pressure, visual fields,
      stereo optic disc photography and ODF measured on their initial visit. When
      venous pulsation was spontaneous, the ODF was said to be 0 g. At re-examination,
      central corneal thickness and blood pressure were also measured. Initial and
      subsequent optic disc photographs were compared and graded into those that had
      increased excavation and those that had remained stable. The relationship between
      increased excavation (recorded as a binary response) and the measured variables
      was modelled using a multiple mixed effects logistic regression. RESULTS: ODF at
      the initial visit was strongly predictive of increased excavation (p = 0.004,
      odds ratio 1.16/g, range 0-60 g), with greater predictive value in women than in
      men (p = 0.004). Visual field mean deviation was predictive of increased
      excavation (p = 0.044), as was optic nerve haemorrhage in association with older
      age (p = 0.038). Central corneal thickness was not significantly predictive of
      increased excavation (p = 0.074) after having adjusted for other variables.
      CONCLUSION: ODF measurement seems to be strongly predictive of the patient's risk
      for increased optic disc excavation. This suggests that ODF measurement may have
      predictive value in assessing the likelihood of glaucoma progression.

PMID- 17035271
TI  - Contrast sensitivity and visual hallucinations in patients referred to a low
      vision rehabilitation clinic.
AB  - AIM: To examine the association of reported visual hallucinations and measured
      visual parameters in adult patients referred for low vision rehabilitation.
      METHODS: All patients (N = 225) referred to a low vision rehabilitation clinic
      for a calendar year were asked a standardised question about symptoms of formed
      visual hallucinations. Best corrected visual acuity and contrast sensitivity
      using the Pelli-Robson chart were measured. We conducted multiple logistic
      regression analysis of the association between visual hallucinations and visual
      parameters. RESULTS: Of the total cohort, 78 (35%) reported visual
      hallucinations. Visual acuity and contrast sensitivity were considered in four
      quartiles. In multiple logistic regression controlling for contrast sensitivity,
      age, gender, report of depression and independence, measured acuity in each of
      the poorer three categories (compared to the best) was not associated with
      reported hallucinations. Contrast sensitivity in the three poorer quartiles
      (compared to the best) was strongly associated with the report of hallucinations
      (OR 4.1, CI 1.1, 15.9; OR 10.5, CI 2.6, 42.1; OR 28.1, CI 5.6, 140.9) after
      controlling for acuity, age, sex, depression and independence. CONCLUSIONS:
      Lowest contrast sensitivity was the strongest predictor of reported
      hallucinations after adjusting for visual acuity.

PMID- 17035272
TI  - Clinical characterisation and molecular analysis of Wagner syndrome.
AB  - AIM: To detail the clinical findings in a British family with molecularly
      characterised Wagner syndrome. BACKGROUND: Only in the last year has the specific
      genetic defect in Wagner syndrome been identified, and the background literature
      of the molecular genetics is outlined. Clinical and laboratory findings in a
      second case of Wagner syndrome are included to highlight difficulties that can be
      encountered when identifying pathogenic mutations for disorders arising in
      complex genes. METHODS: Mutation screening was performed using PCR and RT-PCR.
      RESULTS: A heterozygous mutation was found converting the donor splice site of
      exon 8 of the chondroitin sulphate proteoglycan 2 (CSPG2). This is the same
      mutation that has been reported in the original Wagner pedigree. The main
      clinical features of Wagner syndrome are vitreous syneresis, thickening and
      incomplete separation of the posterior hyaloid membrane, chorioretinal changes
      accompanied by subnormal electroretinographic responses, an ectopic fovea and
      early-onset cataract. A clinical feature present in this family, but previously
      undescribed, is anterior uveitis without formation of synechiae. Wagner syndrome
      has a progressive course, resulting in loss of vision even in the absence of
      retinal detachment. CONCLUSION: On a background of considerable confusion
      regarding the distinction between Wagner syndrome and predominantly ocular
      Stickler syndrome, it is now apparent the that two conditions are both clinically
      and genetically distinct. This report summarises the clinical findings in Wagner
      syndrome and extends the phenotypic characteristics.

PMID- 17035273
TI  - Mechanical energy from intraocular instruments cause emulsification of silicone
      oil.
AB  - AIM: The complications of intraocular silicone oil include emulsification, which
      may lead to vision-threatening disorders such as keratopathy, secondary glaucoma
      and retinopathy. The authors study the effect of mechanical energy from surgical
      instruments on the emulsification of silicone oil. METHODS: Three different
      handpieces (phacofragmentation, phacoemulsification, high-speed vitrectomy) were
      placed at the interface of balanced salt solution and silicone oil (1000 and 5000
      cst, 200 fluid; Dow Corning). The phacofragmentation handpiece was evaluated over
      different ultrasound powers and duration. Emulsification was quantified with
      phase-contrast microscopy and manual counting of digital photographs by a masked
      examiner. In addition, phacoemulsification was performed in the anterior chamber
      of a human ex vivo eye with full-fill silicone oil. RESULTS: Emulsification
      increases with higher phacofragmentation power and duration and is greater for
      1000 cst silicone oil. Emulsification of silicone oil occurs with
      phacoemulsification and high-speed vitrectomy handpieces. CONCLUSIONS: The energy
      from surgical handpieces is sufficient to result in silicone oil emulsification.

PMID- 17035274
TI  - Adalimumab in the therapy of uveitis in childhood.
AB  - PURPOSE: Chronic anterior uveitis in children often takes a serious course.
      Despite various immunosuppressive drugs some children do not respond sufficiently
      and there is a high risk of them becoming seriously disabled. Anti-TNF alpha
      therapy has been shown by our group and others to be mostly ineffective
      (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic
      reactions. Here we report on 18 young patients treated with Adalimumab (Humira),
      a complete humanised anti-TNF alpha antibody. METHODS: We retrospectively
      analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks,
      when ineffective every week); 17 had juvenile idiopathic arthritis, one was
      without detectable underlying disease. The age at onset of arthritis varied from
      0.5-15 years and for uveitis from 2-19 years. Patients were included when the
      previous anti-inflammatory therapy had been ineffective. It consisted of systemic
      steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n
      = 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n =
      3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a)
      effective: no relapse or more than two relapses less than before treatment, (b)
      mild: one relapse less than before treatment, (c) no response: no change in
      relapse rate and (d) worsening: more relapses under treatment than before. The
      grading for arthritis (depending on the clinical findings), using three out of
      six parameters of the ACR PED Criteria, was: effective, mild, no response,
      worsening. RESULTS: For arthritis (n = 16) the response to Adalimumab was
      effective in 10 of 16 patients, mild in three patients, three did not respond.
      For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one
      patient did not show any effect. After a very good response initially a shorter
      application time had to be used to maintain the good anti-inflammatory effect in
      one child. Additional immunosuppressive treatment was used in seven of the
      effectively treated children. Due to elevation of liver enzymes in one patient,
      who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions
      or increased frequency of infections since start of Adalimumab treatment was
      reported. CONCLUSIONS: For our group of children with long lasting disease our
      results show that Adalimumab was effective or mildly effective against the
      arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis
      are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems
      to be much more effective against uveitis than Etanercept. Anaphylactic
      reactions, found in a previous study from our group after Infliximab treatment,
      were not seen with Adalimumab. The necessary dosage and the treatment period,
      which probably have to be defined individually for each patient, remain unclear.

PMID- 17035275
TI  - Autologous retinal pigment epithelium-choroid sheet transplantation in age
      related macular degeneration: morphological and functional results.
AB  - OBJECTIVE: To evaluate the outcome of autologous retinal pigment epithelium (RPE)
      choroid sheet transplantation after removal of a subfoveal choroidal
      neovascularisation (CNV) in patients with age related macular degeneration (AMD).
      METHODS: RPE-choroid sheet transplantation was performed in 10 consecutive
      patients with exudative AMD (n = 9) or geographic atrophy (n = 1). After CNV
      extraction, an autologous RPE-choroid patch was translocated from the
      midperiphery under the macula. Follow-up was between 6 and 12 months. Visual
      acuity testing and microperimetry (Nidek-MP1) as well as autofluorescence,
      fluorescein and indocyanine green (ICG) angiography were performed and the data
      were analysed retrospectively. RESULTS: Visual acuity (logarithm of minimum angel
      of resolution) before operation ranged from 0.7 to 1.8 (mean 1.37) and after
      operation from 0.4 to 1.6 (mean 1.24). Visual acuity after operation improved in
      seven patients (by a mean of 0.26), remained stable in one patient and decreased
      in two patients. Microperimetry showed light sensitivity and fixation on the
      sheet in five cases. ICG angiography demonstrated perfusion through the RPE
      choroid graft in nine patients. Postoperative complications included retinal
      detachment (n = 1) and epiretinal membrane formation (n = 2). The patient with
      geographic atrophy developed a CNV after surgery. CONCLUSIONS: Autologous RPE
      choroid sheet transplantation is feasible and a comparatively safe procedure.
      Microperimetry showed fixation and light perception over the graft with a
      moderate increase in mean visual acuity.

PMID- 17035276
TI  - Clinical features of dysthyroid optic neuropathy: a European Group on Graves'
      Orbitopathy (EUGOGO) survey.
AB  - BACKGROUND: This study was performed to determine clinical features of dysthyroid
      optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON
      presented to seven European centres during one year. Local protocols for thyroid
      status, ophthalmic examination and further investigation were used. Each eye was
      classified as having definite, equivocal, or no DON. RESULTS: Graves'
      hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94
      eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was
      4/7 but 25% scored 3 or less, indicating severe inflammation was not essential.
      Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes.
      Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the
      DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm
      (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed
      apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat
      prolapse were infrequently reported. CONCLUSION: Patients with DON may not have
      severe proptosis and orbital inflammation. Optic disc swelling, impaired colour
      vision and radiological evidence of apical optic nerve compression are the most
      useful clinical features in this series.

PMID- 17035277
TI  - Risks of relapse in patients with acute anterior uveitis.
AB  - AIM: To quantify the rate of recurrence of acute anterior uveitis (AAU), and
      evaluate the influence of associated risk factors. METHODS: We retrospectively
      reviewed the case notes of 185 patients with acute anterior uveitis, from their
      time of presentation to August 2001. The time to the first three recurrences of
      AAU from the onset of the disease was recorded, as well as the site of
      recurrence. Information regarding risk factors (for example (HLA-B27) status,
      spondyloarthropathy (SpA), family history of AAU/SpA and history of non-specific
      joint pain) were also collected. RESULTS: Patients were followed up until their
      third relapse, or up to the censoring date (August 2001) if less than three
      relapses had occurred. The median length of follow-up was 35 months. One hundred
      and twenty-two patients (66%) developed at least one relapse and 67 (36%) had
      three or more relapses. Kaplan-Meier estimate of median interval between disease
      onset and the first relapse was 24 months 95% CI (16 to 34) and between the first
      and second relapse was 14 months 95% CI (9 to 22), and was 15 months 95% CI (10
      to 25) months between the second and third relapse. Using Cox regression only the
      number of previous relapses was significantly associated with the risk of AAU
      recurrence. There was no significant association between other reported risk
      factors and the risk of relapse, and neither did any risk factor significantly
      modify the association between previous relapses and AAU recurrence (p>0.066 for
      all interactions). There was a borderline significant difference in survival
      according to the laterality pattern of recurrences (ipsilateral, alternate, or
      bilateral) with a slightly greater than expected number of events in those with
      bilateral recurrence (p = 0.048). CONCLUSION: Patients with previous relapse(s)
      of AAU have a greater risk of AAU recurrence compared to those at disease onset
      but the risk of recurrence appears not to increase in a dose-response manner with
      increasing number of previous relapses. Demographic and extraocular features do
      not appear to influence the rate, or risk of recurrence of AAU.

PMID- 17035278
TI  - Identification of resident and inflammatory bone marrow derived cells in the
      sclera by bone marrow and haematopoietic stem cell transplantation.
AB  - AIMS: To characterise bone marrow derived cells in the sclera under normal and
      inflammatory conditions, we examined their differentiation after transplantation
      from two different sources, bone marrow and haematopoietic stem cells (HSC).
      METHODS: Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice
      were transplanted into irradiated wild-type mice. At 1 month after
      transplantation, mice were sacrificed and their sclera examined by histology,
      immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron
      microscopy. To investigate bone marrow derived cell recruitment under
      inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in
      transplanted mice. RESULTS: GFP positive cells were distributed in the entire
      sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the
      total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)%
      (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c
      (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC
      transplantation. Transmission and scanning electron microscopy revealed antigen
      presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of
      GFP (+) cells developed into the sclera. CONCLUSION: We have provided direct and
      novel evidence for the migration of bone marrow and HSC cells into the sclera
      differentiating into macrophages and dendritic cells. Vast infiltration of bone
      marrow and HSC cells was found to be part of the inflammatory process in EAU.

PMID- 17035279
TI  - Photoreceptor mitochondrial oxidative stress in early experimental autoimmune
      uveoretinitis.
AB  - AIMS: In early S-antigen induced experimental uveitis (EAU), photoreceptor
      mitochondrial proteins are nitrated prior to macrophage infiltration of the
      retina, suggesting that oxidative stress is an initial event in the development
      of EAU. We attempted to detect the oxidative stress and localise it in the EAU
      retina. METHODS: Lewis rats were immunised with S-antigen in complete Freund's
      adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals
      served as controls. Immunised and non-immunised animals were killed on day 5 and
      subsequent days. Isolated retinas were processed for inducible nitric oxide
      synthase (iNOS), tumour necrosis factor (TNF)alpha, interferon (IFN)gamma,
      interleukin (IL)Ialpha and CD28 expression by real time polymerase chain
      reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of
      EAU. Oxidative stress was detected by 2', 7'-dichlorodihydrofluorescein diacetate
      and localised by a mitochondrial specific marker. Leucocyte and T cell
      infiltration in the retina/choroid was evaluated by immunohistochemistry.
      RESULTS: The iNOS, TNFalpha, IFNgamma, IL1alpha and CD28 transcripts were
      significantly upregulated on day 5 in EAU, and iNOS was colocalised with
      cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen
      primarily in the photoreceptor mitochondria. Occasional T cells were present in
      the retina at this stage. CONCLUSIONS: During early EAU, mitochondrial oxidative
      stress is selectively noted in the photoreceptor inner segments. The oxidative
      stress appears to result from iNOS upregulation in the photoreceptor mitochondria
      and cytokine generation in the retina by a few antigen specific infiltrating T
      cells.

PMID- 17035280
TI  - The prevalence of refractive errors among schoolchildren in Dezful, Iran.
AB  - AIM: To determine the prevalence of refractive errors among schoolchildren in
      urban and rural areas of Dezful County, Iran. METHODS: In a cross-sectional
      study, using random cluster sampling, 5721 Dezful schoolchildren were selected
      from 39 clusters. The participants in the study totalled 5544; 3673 elementary
      and middle school students and 1871 high school students. For the former group,
      cycloplegic refraction and for the latter, non-cycloplegic refraction was tested.
      In all participants, uncorrected visual acuity and best corrected visual acuity
      were determined, and those with a visual acuity of 20/40 or worse, underwent a
      complete ophthalmic examination to determine the cause of visual impairment. A
      spherical equivalent of -0.5 diopter (D) or worse was defined as myopia, +2.0 D
      or more was defined as hyperopia, and a cylinder refraction greater than 0.75 D
      was considered astigmatism. RESULTS: The uncorrected visual acuity was 20/40 or
      worse in the better eye of 224 schoolchildren (3.8% of participants). This figure
      (percentage) was 14 (0.03%) based on their best corrected visual acuity and 96
      (1.7%) with their presenting vision. According to results of cycloplegic
      refraction, 3.4% (95% confidence interval (CI), 2.5 to 4.4) of the primary and
      middle school students were myopic and 16.6% (95% CI, 13.6 to 19.7) were
      hyperopic. For high school students, these rates were 2.1% (95% CI, 0.7 to 3.5)
      and 33.0% (95% CI, 24.9 to 41.1), respectively, with non-cycloplegic refraction.
      In the multivariate logistic regression for primary and middle school students,
      myopia was correlated with age (p = 0.030), and hyperopia was correlated with age
      (p<0.001) and area of residence (p = 0.007). In high school students, hyperopia
      again showed a correlation with their area of residence (p = 0.029). CONCLUSION:
      The present study reveals the considerable prevalence rates of refractive errors
      among schoolchildren in Dezful County and the high rate of an unmet need for
      their correction. Although myopia is not very prevalent, the high rate of
      hyperopia in the studied population emphasises its need for attention.

PMID- 17035281
TI  - Dacryocystorhinostomy in patients lacking an ipsilateral nasal cavity.
AB  - Dacryocystorhinostomy (DCR) remains the surgery of choice for the treatment of
      epiphora secondary to nasolacrimal duct (NLD) obstruction. It involves creating a
      direct soft-tissue anastomosis between the lacrimal sac and the ipsilateral nasal
      cavity, via an osteotomy created by removal of the floor of the lacrimal fossa
      and surrounding bone. Successful surgery clearly requires the presence of a nasal
      space and absence of this poses a surgical challenge. We describe three patients
      with absent nasal cavity on the side of lacrimal obstruction, where DCR was
      performed by the creation of an anastomosis between the lacrimal sac and the
      contralateral nasal space.

PMID- 17035282
TI  - Ocular complications in heart, lung and heart-lung recipients.
AB  - AIM: To prospectively assess ocular morbidity and the need for ocular screening
      in patients on long term, high dose immunosuppression for the maintenance of
      solid organ transplants. METHODS: Dilated ocular examinations were performed on
      patients receiving immunosuppression for the maintenance of heart, lung and heart
      lung transplants. Patients were examined repeatedly in the post transplant
      period. RESULTS: Of the 115 transplant recipients examined 62 (54%) had ocular
      findings. The most common findings were cataracts (17% of those examined)
      followed by hypertensive change (8%), chorioretinal scarring (5%) and diabetic
      retinopathy (3%). One patient developed ocular infective complications following
      surgery due to Aspergillus spp. endophthalmitis. 18 patients (16%) were
      symptomatic at examination with the most common symptom being blurred vision. The
      most common finding in symptomatic patients was cataract with almost a quarter of
      patients having posterior subcapsular lens opacity that could be attributed to
      steroid therapy. CONCLUSION: Patients had surprising low incidences of ocular
      infective complications despite previous reports. It is likely that this is due
      to improved immunosuppression regimes and improved monitoring of
      immunosuppression in the early post-transplant period. The screening of
      asymptomatic individuals following heart, lung or heart-lung transplantation was
      not supported by this study.

PMID- 17035283
TI  - Accuracy of GDx VCC, HRT I, and clinical assessment of stereoscopic optic nerve
      head photographs for diagnosing glaucoma.
AB  - AIMS: To determine and compare the accuracy and reproducibility of GDx variable
      cornea compensation (VCC) scanning laser polarimetry (SLP) with VCC, Heidelberg
      retina tomograph (HRT) I confocal scanning laser ophthalmoscopy (CSLO), and
      clinical assessment of stereoscopic optic nerve head (ONH) photographs for
      diagnosing glaucoma. METHODS: One eye each of 40 healthy subjects, 48 glaucoma
      patients, and six patients with ocular hypertension were measured with SLP-VCC
      and CSLO. Simultaneous stereoscopic ONH photographs were also obtained. Sixteen
      photographs of healthy and glaucomatous eyes were duplicated for assessing
      intraobserver agreement. Four glaucoma specialists, four general
      ophthalmologists, four residents in ophthalmology, and four optometrists
      classified the ONH photographs as normal or glaucomatous. For SLP-VCC, the nerve
      fiber indicator (NFI) was evaluated. For CSLO, the Moorfields regression analysis
      (MRA) and the Bathija linear discriminant function (LDF) were used. Sensitivity,
      specificity, percentage of correctly classified eyes, and intra- and
      interobserver agreement, expressed as kappa (kappa) were calculated. RESULTS: SLP
      VCC had the highest diagnostic accuracy, with a sensitivity, specificity, and
      overall correct classification of 91.7%, 95.0% and 93.2%, respectively. CSLO,
      expressed as Bathija LDF and MRA, had a diagnostic accuracy comparable to
      glaucoma specialists and general ophthalmologists with an overall accuracy of
      89.8%, 86.4%, 86.7% and 85.2%, respectively. Residents classified the fewest eyes
      correctly. Intraobserver agreement for classifying the ONH photographs ranged
      between 0.48 (within residents) and 0.78 (within glaucoma specialists). The
      interobserver agreement ranged between 0.45 (between residents) and 0.74 (between
      glaucoma specialists). The agreement between observers and CSLO MRA (kappa, 0.68)
      was statistically significantly higher (p<0.001; paired t-test) than between
      observers and SLP-VCC NFI (kappa, 0.60) and CSLO Bathija LDF (kappa, 0.62).
      CONCLUSION: Automated analysis of measurements with GDx VCC and HRT had a similar
      diagnostic accuracy for glaucoma as classification of stereoscopic ONH
      photographs by glaucoma specialists, thus bringing all eye-care professionals to
      this desirable level. The intra- and interobserver agreement for ONH analysis was
      only moderate to good. We think these imaging techniques may assist clinicians in
      diagnosing glaucoma.

PMID- 17035284
TI  - Morphological and physiological responses of rice (Oryza sativa) to limited
      phosphorus supply in aerated and stagnant solution culture.
AB  - BACKGROUND AND AIMS: Rain-fed lowland rice commonly encounters stresses from
      fluctuating water regimes and nutrient deficiency. Roots have to acquire both
      oxygen and nutrients under adverse conditions while also acclimating to changes
      in soil-water regime. This study assessed responses of rice roots to low
      phosphorus supply in aerated and stagnant nutrient solution. METHODS: Rice (Oryza
      sativa 'Amaroo') was grown in aerated solution with high P (200 micro m) for 14
      d, then transferred to high or low (1.6 micro m) P supply in aerated or stagnant
      solution for up to 8 d. KEY RESULTS: After only 1 d in stagnant conditions, root
      radial oxygen loss (ROL) had decreased by 90 % in subapical zones, whereas near
      the tip ROL was maintained. After 4 d in stagnant conditions, maximum root length
      was 11 % less, and after 8 d, shoot growth was 25 % less, compared with plants in
      aerated solution. The plants in stagnant solution had up to 19 % more
      adventitious roots, 24 % greater root porosity and 26 % higher root/shoot ratio.
      Rice in low P supply had fewer tillers in both stagnant and aerated conditions.
      After 1-2 d in stagnant solution, relative P uptake declined, especially at low P
      supply. Aerated roots at low P supply maintained relative P uptake for 4 d, after
      which uptake decreased to the same levels as in stagnant solution. CONCLUSIONS:
      Roots responded rapidly to oxygen deficiency with decreased ROL in subapical
      zones within 1-2 d, indicating induction of a barrier to ROL, and these changes
      in ROL occurred at least 2 d before any changes in root morphology, porosity or
      anatomy were evident. Relative P uptake also decreased under oxygen deficiency,
      showing that a sudden decline in root-zone oxygen adversely affects P nutrition
      of rice.

PMID- 17035285
TI  - Upper limb pain in primary care: health beliefs, somatic distress, consulting and
      patient satisfaction.
AB  - BACKGROUND: Beliefs and mental well-being could influence decisions to consult
      about upper limb pain and satisfaction with care. OBJECTIVES: To describe beliefs
      about upper limb pain in the community and explore associations of beliefs and
      mental health with consulting and dissatisfaction. METHODS: Questionnaires were
      mailed to 4998 randomly chosen working-aged patients from general practices in
      Avon. We asked about upper limb pain, consulting, beliefs about symptoms,
      dissatisfaction with care, somatizing tendency (using elements of the Brief
      Symptom Inventory) and mental well-being (using the Short-Form 36). Associations
      were explored by logistic regression. RESULTS: Among 2632 responders, 1271
      reported arm pain during the past 12 months, including 389 consulters. A third or
      more of responders felt that arm pain sufferers should avoid physical activity,
      that problems would persist beyond 3 months, that a doctor should be seen
      straightaway and that neglect could lead to permanent harm. Consulters were
      significantly more likely to agree with these statements than other upper limb
      pain sufferers. The proportion of consultations attributable to such beliefs was
      substantial. Dissatisfaction with care was commoner in those with poor mental
      health: the OR for being dissatisfied (worst versus best third of the
      distribution) was 3.2 (95% CI 1.2-8.5) for somatizing tendency and 2.4 (95% CI
      1.3-4.7) for SF-36 score. Both factors were associated with dissatisfaction about
      doctors' sympathy, communication and care in examining. CONCLUSIONS: Negative
      beliefs about upper limb pain are common and associated with consulting.
      Somatizers and those in poorer mental health tend, subsequently, to feel
      dissatisfied with care.

PMID- 17035286
TI  - A qualitative study to identify factors influencing COXIB prescribed by family
      physicians for musculoskeletal disorders.
AB  - INTRODUCTION: Cyclo-oxygenase-2 inhibiting (COXIB) anti-inflammatories have been
      the drug class prescribed for a large number of cases of musculoskeletal (MSK)
      disorders in Canada over the past 5 years. The Alberta Improvements for MSK
      Disorders (AIMS) initiative sought to better understand the COXIB prescribing
      situation by funding several studies. The objective of this qualitative study was
      to determine the factors underlying primary care physicians' medication
      prescribing behaviour during an office visit for an MSK disorder, with particular
      emphasis on the prescribing of COXIBs. METHODS: The target respondents were
      Alberta primary care physicians chosen from a stratified random sample to meet a
      wide range of characteristics. Individual, semi-structured interviews were used
      to assess decision pathways in four real cases chosen by the physician. A total
      of 19 interviews were conducted and analysed using an analytic inductive
      approach. RESULTS: Factors judged as being important to decision pathways in
      relation to COXIB prescribing for MSK disease included safety, patient
      characteristics, affordability to patients, availability of samples, drug company
      marketing practices, habit formation, time contstraints, previous clinical
      experience of doctors and/or patient with certain drugs and doctors' perception
      of absolute versus relative risk. Interpretation. Most physicians preferentially
      prescribed COXIBs subsequent to a complicated, multifactorial, but essentially
      patient-centred, decision-making process.

PMID- 17035287
TI  - Screening for depression in primary care.

PMID- 17035288
TI  - Severity of illness and the use of paracetamol in febrile preschool children; a
      case simulation study of parents' assessments.
AB  - OBJECTIVE: Misconceptions and exaggerated fear of fever may divert parents'
      attention from more predictive symptoms of childhood illness, such as appetite
      and level of activity. This study aims at exploring how specific predefined
      characteristics of febrile preschool children affected parents' assessment of the
      severity of the condition and the perceived need for treatment with paracetamol.
      METHODS: Parents judged 24 constructed cases of febrile children with different
      levels of fever, appetite and activity, occurring at different times of the day.
      For each case they decided whether the child was moderately or severely ill, and
      whether or not they would prefer to administer paracetamol. Parents' decision
      making was examined by discriminant analyses. RESULTS: Of 466 invited parents,
      267 supplied information about their families and 205 accepted to participate in
      judging constructed cases of febrile children. A total of 159 parents responded
      to all cases. When evaluating the severity of the illness, 119 parents (75%)
      responded to one or more of the four cues describing illness. Only one of four
      cues was used by 80 parents (67%), and 86 (72%) parents emphasized fever. When
      deciding to give paracetamol, one or more of four cues was used by 102 parents
      (64%), while 72 parents (71%) used only one cue, and 92 parents (90%) emphasized
      fever. CONCLUSIONS: Parents focus on fever when they evaluate febrile illness and
      decide whether or not to give paracetamol. Educating parents to focus on their
      child's level of appetite or activity may improve management, especially when
      judgement is based on only one or two cues.

PMID- 17035289
TI  - Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis.
AB  - We here report essential roles of the Bmp-binding protein crossveinless 2 (Cv2;
      Bmper) in mouse organogenesis. In the null Cv2 mutant mouse, gastrulation occurs
      normally, but a number of defects are found in Cv2-expressing tissues such as the
      skeleton. Cartilage differentiation by Bmp4 treatment is reduced in cultured Cv2(
      /-) fibroblasts. Moreover, the defects in the vertebral column and eyes of the
      Cv2(-/-) mouse are substantially enhanced by deleting one copy of the Bmp4 gene,
      suggesting a pro-Bmp role of Cv2 in the development of these organs. In addition,
      the Cv2(-/-) mutant exhibits substantial defects in Bmp-dependent processes of
      internal organ formation, such as nephron generation in the kidney. This kidney
      hypoplasia is synergistically enhanced by the additional deletion of Kcp (Crim2)
      which encodes a pro-Bmp protein structurally related to Cv2. This study
      demonstrates essential pro-Bmp functions of Cv2 for locally restricted signal
      enhancement in multiple aspects of mammalian organogenesis.

PMID- 17035290
TI  - Jagged 1 is a beta-catenin target gene required for ectopic hair follicle
      formation in adult epidermis.
AB  - The Wnt and Notch signalling pathways regulate hair follicle maintenance, but how
      they intersect is unknown. We show that Notch signalling is active in the hair
      follicle pre-cortex, a region of high Wnt activity, where commitment to hair
      lineages occurs. Deletion of jagged 1 (Jag1) results in inhibition of the hair
      growth cycle and conversion of hair follicles into cysts of cells undergoing
      interfollicular epidermal differentiation. Conversely, activation of Notch in
      adult epidermis triggers expansion of the base of the hair follicle, sebaceous
      gland enlargement and abnormal clumping of the follicles. In adult epidermis, the
      induction of new hair follicle formation by beta-catenin is prevented by blocking
      Notch signalling pharmacologically or through Jag1 deletion. Conversely,
      activation of both pathways accelerates growth and differentiation of ectopic
      follicles. beta-catenin stimulates Notch signalling by inducing Jag1
      transcription. We conclude that the Notch pathway acts downstream of the Wnt/beta
      catenin pathway to determine epidermal cell fate.

PMID- 17035291
TI  - Uncoupling dorsal-mediated activation from dorsal-mediated repression in the
      Drosophila embryo.
AB  - The Rel family transcription factor Dorsal patterns the dorsoventral axis of the
      Drosophila embryo by activating genes such as twist and snail and repressing
      genes such as decapentaplegic and zerknullt. Dorsal represses transcription by
      recruiting the co-repressor Groucho. However, repression occurs only when Dorsal
      binding sites are close to binding sites for other factors that also bind
      Groucho. The need for additional factors to assist Dorsal in repression may
      result from the intrinsically weak interaction between Dorsal and Groucho. To
      test this idea, we generated a Dorsal variant containing a high-affinity Groucho
      recruitment motif at its C terminus. As predicted, this variant functions as a
      dedicated repressor, silencing decapentaplegic and zerknullt while failing to
      activate twist and snail. We also converted Dorsal into a dedicated activator by
      replacing its weak Groucho-recruitment motif with heterologous activation
      domains. Although the dedicated activator alleles fail to repress decapentaplegic
      and zerknullt in the syncytial blastoderm embryo, they are able to pattern the
      dorsoventral axis. This indicates that dorsoventral patterning is not dependent
      upon Dorsal-mediated repression, reflecting the existence of redundant mechanisms
      to block Decapentaplegic signaling.

PMID- 17035292
TI  - Genetic analysis of EphA-dependent signaling mechanisms controlling topographic
      mapping in vivo.
AB  - Ephrin/Eph ligands and receptors are best known for their prominent role in
      topographic mapping of neural connectivity. Despite the large amount of work
      centered on ephrin/Eph-dependent signaling pathways in various cellular contexts,
      the molecular mechanisms of action of Eph receptors in neural mapping, requiring
      dynamic interactions between complementary gradients of ephrins and Eph
      receptors, remain largely unknown. Here, we investigated in vivo the signaling
      mechanisms of neural mapping mediated by the EphA4 receptor, previously shown to
      control topographic specificity of thalamocortical axons in the mouse
      somatosensory system. Using axon tracing analyses of knock-in mouse lines
      displaying selective mutations for the Epha4 gene, we determined for the first
      time which intracellular domains of an Eph receptor are required for topographic
      mapping. We provide direct in vivo evidence that the tyrosine kinase domain of
      EphA4, as well as a tight regulation of its activity, are required for
      topographic mapping of thalamocortical axons, whereas non-catalytic functional
      modules, such as the PDZ-binding motif (PBM) and the Sterile-alpha motif (SAM)
      domain, are dispensable. These data provide a novel insight into the molecular
      mechanisms of topographic mapping, and constitute a physiological framework for
      the dissection of the downstream signaling cascades involved.

PMID- 17035293
TI  - DNA supercoiling factor contributes to dosage compensation in Drosophila.
AB  - DNA supercoiling factor (SCF) is a protein capable of generating negative
      supercoils in DNA in conjunction with topoisomerase II. To clarify the biological
      functions of SCF, we introduced a heritable SCF RNAi into Drosophila. Upon
      knockdown of SCF, we observed male lethality and male-specific reduction in the
      expression levels of X-linked genes. SCF functionally interacts with components
      of the MSL complex, which are required for dosage compensation via
      hypertranscription of the male X chromosome. Moreover, SCF colocalizes with the
      MSL complex along the male X chromosome. Upon overexpression of SCF, the male X
      chromosome had a bloated appearance. This phenotype was dependent on the histone
      acetyltransferase MOF and was suppressed by simultaneous overexpression of ISWI.
      These findings demonstrate that SCF plays a role in transcriptional activation
      via alteration of chromatin structure and provide evidence that SCF contributes
      to dosage compensation.

PMID- 17035294
TI  - Compartments and the control of growth in the Drosophila wing imaginal disc.
AB  - The mechanisms that control organ growth are among the least known in
      development. This is particularly the case for the process in which growth is
      arrested once final size is reached. We have studied this problem in the wing
      disc of Drosophila, the developmental and growth parameters of which are well
      known. We have devised a method to generate entire fast-growing Minute(+) (M(+))
      discs or compartments in slow developing Minute/+ (M/+) larvae. Under these
      conditions, a M(+) wing disc gains at least 20 hours of additional development
      time. Yet it grows to the same size of Minute/+ discs developing in M/+ larvae.
      We have also generated wing discs in which all the cells in either the anterior
      (A) or the posterior (P) compartment are transformed from M/+ to M(+). We find
      that the difference in the cell division rate of their cells is reflected in
      autonomous differences in the developmental progression of these compartments:
      each grows at its own rate and manifests autonomous regulation in the expression
      of the developmental genes wingless and vestigial. In spite of these differences,
      ;mosaic' discs comprising fast and slow compartments differentiate into adult
      wings of the correct size and shape. Our results demonstrate that imaginal discs
      possess an autonomous mechanism with which to arrest growth in anterior and
      posterior compartments, which behave as independent developmental units. We
      propose that this mechanism does not act by preventing cell divisions, but by
      lengthening the division cycle.

PMID- 17035295
TI  - Frizzled/RYK mediated signalling in axon guidance.

PMID- 17035296
TI  - Toronto's Health Department in action: influenza in 1918 and SARS in 2003.
AB  - This article compares the Toronto Health Department's role in controlling the
      1918 influenza epidemic with its activities during the SARS outbreak in 2003 and
      concludes that local health departments are the foundation for successful disease
      containment, provided that there is effective coordination, communication, and
      capacity. In 1918, Toronto's MOH Charles Hastings was the acknowledged leader of
      efforts to contain the disease, care for the sick, and develop an effective
      vaccine, because neither a federal health department nor an international body
      like WHO existed. During the SARS outbreak, Hastings's successor, Sheela Basrur,
      discovered that nearly a decade of underfunding and new policy foci such as
      health promotion had left the department vulnerable when faced with a potential
      epidemic. Lack of cooperation by provincial and federal authorities added further
      difficulties to the challenge of organizing contact tracing, quarantine, and
      isolation for suspected and probable cases and providing information and
      reassurance to the multi-ethnic population. With growing concern about a flu
      pandemic, the lessons of the past provide a foundation for future communicable
      disease control activities.

PMID- 17035297
TI  - Mechanisms of endothelial cell protection by blockade of the JAK2 pathway.
AB  - Inhibition of the JAK2/STAT pathway has been implicated recently in
      cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes.
      The advent of JAK2-specific inhibitors provides a practical tool for the study of
      this pathway in different cellular types. An interest in finding methods to
      improve endothelial cell (EC) resistance to injury led us to examine the effect
      of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways
      involved in JAK2/STAT inhibition-related actions were examined. Our results
      reveal, for the first time, that blockade of JAK2 with the tyrosine kinase
      inhibitor AG490 strongly protects cultured EC against cell detachment-dependent
      death and serum deprivation and increases reseeding efficiency. Confirmation of
      the specificity of the effects of JAK2 inhibition was attained by finding
      protective effects on transfection with a dominant negative JAK2. Furthermore,
      AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of
      mechanism, treatment with AG490 induces several relevant responses, both in
      monolayer and detached cells. These mechanisms include the following: 1) Increase
      and nuclear translocation of the active, dephosphorylated form of beta-catenin.
      In functional terms, this translocation is transcriptionally active, and its
      protective effect is further supported by the stimulation of EC cytoprotection by
      transfectionally induced excess of beta-catenin. 2) Increase of platelet
      endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and
      phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase
      (GSK)3alpha/beta. The present findings imply potential practical applications of
      JAK2 inhibition on EC. These applications affect not only EC in the monolayer but
      also circulating detached cells and involve mechanistic interactions not
      previously described.

PMID- 17035298
TI  - Biologically active lipids promote trafficking and membrane association of Rac1
      in insulin-secreting INS 832/13 cells.
AB  - Despite emerging evidence to suggest that glucose-stimulated insulin secretion
      (GSIS) requires membrane targeting of specific small G proteins (e.g., Rac1),
      very little is known with regard to the precise mechanisms underlying subcellular
      trafficking of these proteins in the glucose-stimulated islet beta-cell. We
      previously reported activation of small G proteins by biologically active lipids
      via potentiation of relevant GDP/GTP exchange activities within the beta-cell.
      Herein, we studied putative regulatory roles for these lipids in the trafficking
      and membrane association of Rac1 in cell-free preparations derived from INS
      832/13 beta-cells. Incubation of INS 832/13 cell lysates with
      polyphosphoinositides (e.g., PIP(2)), phosphatidic acid, phosphatidylcholine, and
      phosphatidylserine significantly promoted trafficking of cytosolic Rac1 to the
      membrane fraction. Lysophosphatidic acid, but not lysophosphatidylcholine or
      lysophosphatidylserine, also promoted translocation and membrane association of
      Rac1. Arachidonic acid, diacylglycerol, calcium, and cAMP failed to exert any
      clear effects on Rac1 translocation to the membrane. Together, our findings
      provide the first direct evidence in support of our recent hypothesis (Kowluru A,
      Veluthakal R. Diabetes 54: 3523-3529, 2005), which states that generation of
      biologically active lipids, known to occur in the glucose-stimulated beta-cell,
      may mediate targeting of Rac1 to the membrane for optimal interaction with its
      putative effector proteins leading to GSIS.

PMID- 17035299
TI  - Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction
      in astrocytes following in vitro ischemia.
AB  - Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reverse mode operation of
      the Na(+)/Ca(2+) exchanger (NCX) contribute to intracellular Na(+) and Ca(2+)
      overload in astrocytes following oxygen-glucose deprivation (OGD) and
      reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a
      role in mitochondrial Ca(2+) (Ca(m)(2+)) overload and dysfunction. OGD/REOX
      caused a doubling of mitochondrial-releasable Ca(2+) (P < 0.05). When NKCC1 was
      inhibited with bumetanide, the mitochondrial-releasable Ca(2+) was reduced by
      approximately 42% (P < 0.05). Genetic ablation of NKCC1 also reduced Ca(m)(2+)
      accumulation. Moreover, OGD/REOX in NKCC1(+/+) astrocytes caused dissipation of
      the mitochondrial membrane potential (Psi(m)) to 42 +/- 3% of controls. In
      contrast, when NKCC1 was inhibited with bumetanide, depolarization of Psi(m) was
      attenuated significantly (66 +/- 10% of controls, P < 0.05). Cells were also
      subjected to severe in vitro hypoxia by superfusion with a hypoxic, acidic, ion
      shifted Ringer buffer (HAIR). HAIR/REOX triggered a secondary, sustained rise in
      intracellular Ca(2+) that was attenuated by reversal NCX inhibitor KB-R7943. The
      hypoxia-mediated increase in Ca(m)(2+) was accompanied by loss of Psi(m) and
      cytochrome c release in NKCC1(+/+) astrocytes. Bumetanide or genetic ablation of
      NKCC1 attenuated mitochondrial dysfunction and astrocyte death following
      ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a
      perturbation of Ca(m)(2+) homeostasis and mitochondrial dysfunction and cell
      death following in vitro ischemia.

PMID- 17035300
TI  - Kinetics of integrated electron transfer in the mitochondrial respiratory chain:
      random collisions vs. solid state electron channeling.
AB  - Recent evidence, mainly based on native electrophoresis, has suggested that the
      mitochondrial respiratory chain is organized in the form of supercomplexes, due
      to the aggregation of the main respiratory chain enzymatic complexes. This
      evidence strongly contrasts the previously accepted model, the Random Diffusion
      Model, largely based on kinetic studies, stating that the complexes are randomly
      distributed in the lipid bilayer of the inner membrane and functionally connected
      by lateral diffusion of small redox molecules, i.e., coenzyme Q and cytochrome c.
      This review critically examines the experimental evidence, both structural and
      functional, pertaining to the two models and attempts to provide an updated view
      of the organization of the respiratory chain and of its kinetic consequences. The
      conclusion that structural respiratory assemblies exist is overwhelming, whereas
      the expected functional consequence of substrate channeling between the assembled
      enzymes is controversial. Examination of the available evidence suggests that,
      although the supercomplexes are structurally stable, their kinetic competence in
      substrate channeling is more labile and may depend on the system under
      investigation and the assay conditions.

PMID- 17035301
TI  - VOCCs and TREK-1 ion channel expression in human tenocytes.
AB  - Mechanosensitive and voltage-gated ion channels are known to perform important
      roles in mechanotransduction in a number of connective tissues, including bone
      and muscle. It is hypothesized that voltage-gated and mechanosensitive ion
      channels also may play a key role in some or all initial responses of human
      tenocytes to mechanical stimulation. However, to date there has been no direct
      investigation of ion channel expression by human tenocytes. Human tenocytes were
      cultured from patellar tendon samples harvested from five patients undergoing
      routine total knee replacement surgery (mean age: 66 yr; range: 63-73 yr). RT
      PCR, Western blotting, and whole cell electrophysiological studies were performed
      to investigate the expression of different classes of ion channels within
      tenocytes. Human tenocytes expressed mRNA and protein encoding voltage-operated
      calcium channel (VOCC) subunits (Ca alpha(1A), Ca alpha(1C), Ca alpha(1D), Ca
      alpha(2)delta(1)) and the mechanosensitive tandem pore domain potassium channel
      (2PK(+)) TREK-1. They exhibit whole cell currents consistent with the functional
      expression of these channels. In addition, other ionic currents were detected
      within tenocytes consistent with the expression of a diverse array of other ion
      channels. VOCCs and TREK channels have been implicated in mechanotransduction
      signaling pathways in numerous connective tissue cell types. These mechanisms may
      be present in human tenocytes. In addition, human tenocytes may express other
      channel currents. Ion channels may represent potential targets for the
      pharmacological management of chronic tendinopathies.

PMID- 17035302
TI  - Actin-based features negatively regulated by protein kinase C-epsilon.
AB  - Cells exposed to phorbol 12-myristate 13-acetate (PMA) undergo a choreographed
      sequence of morphological changes. Some of these, including stimulation of
      membrane ruffles and the later appearance of stress fibers, rely on remodeling of
      the actin cytoskeleton. Although this process is poorly understood, it is
      important, because the same features are affected during oncogenic
      transformation. PMA also activates protein kinase C (PKC). Enzyme activation is
      followed by degradation. Either process might affect the remodeling of actin. The
      present studies determined whether any PKC isozymes were subject to degradation
      in tracheal epithelial cells by quantifying the amount of each isozyme present
      after PMA exposure. PKC-epsilon was the only isozyme to show declining content
      correlated with increased stress fiber accumulation. Stress fibers increased
      between 5 and 10 h, whereas PKC-epsilon declined to 38% of its starting value
      (95% confidence interval, 10-68%). The relationship could be fit by the function
      F(x) = 0.683 x exp[-0.841(x - 0.387)], where F is the frequency of fiber
      containing cells and x is PKC-epsilon content. Fiber accumulation was further
      investigated after knockdown of PKC-epsilon with RNA interference and antisense
      oligodeoxynucleotide. Knockdown enhanced stress fibers in cells not yet exposed
      to PMA as well as the final frequency of fiber-containing cells after PMA
      exposure. With knockdown at both transcriptional and protein levels,
      approximately 15% of the original content was predicted and achieved, as judged
      from real-time PCR and PKC-epsilon content measurements. The results suggest that
      PKC-epsilon negatively regulates stress fibers, either by directly turning over
      one of their components or by regulating an upstream step affecting fiber
      organization.

PMID- 17035303
TI  - Dynamics of clathrin and adaptor proteins during endocytosis.
AB  - The endocytic adaptor complex AP-2 colocalizes with the majority of clathrin
      positive spots at the cell surface. However, we previously observed that AP-2 is
      excluded from internalizing clathrin-coated vesicles (CCVs). The present studies
      quantitatively demonstrate that AP-2 disengages from sites of endocytosis seconds
      before internalization of the nascent CCV. In contrast, epsin, an alternate
      adaptor for clathrin at the plasma membrane, disappeared, along with clathrin.
      This suggests that epsin remains an integral part of the CCV throughout
      endocytosis. Clathrin spots at the cell surface represent a heterogeneous
      population: a majority (70%) of the spots disappeared with a time course of 4
      min, whereas a minority (22%) remained static for > or =30 min. The static
      clathrin spots undergo constant subunit exchange, suggesting that although they
      are static structures, these spots comprise functional clathrin molecules, rather
      than dead-end aggregates. These results support a model where AP-2 serves a cargo
      sorting function before endocytosis, whereas alternate adaptors, such as epsin,
      actually link cargo to the clathrin coat surrounding nascent endocytic vesicles.
      These data also support a role for static clathrin, providing a nucleation site
      for endocytosis.

PMID- 17035304
TI  - Occurrence of a nonsulfated chondroitin proteoglycan in the dried saliva of
      Collocalia swiftlets (edible bird's-nest).
AB  - Despite their wide occurrence, proteoglycans (PGs) have never been isolated from
      the saliva of higher animals. We found that the Collocalia glycoproteins isolated
      from edible birds'-nests (the dried forms of regurgitated saliva of male
      Collocalia swiftlets) were rich in a PG containing nonsulfated chondroitin
      glycosaminoglycans (GAGs). We have devised a method to isolate a PG from the
      water extract of the white nest built by Aerodramus fuciphagus (white nest
      swiftlets) with a yield of 2-mg PG per gram nest. This PG contained 83% of
      carbohydrates, of which 79% were GalNAc and GlcUA (D-glucuronic acid) in an
      equimolar ratio. By using chondroitin AC lyase, the structure of GAGs in this PG
      was established to be chondroitin ( --> 4GlcUAbeta1 --> 3GalNAcbeta1 --> )(n)
      chains. The average molecular mass of the chondroitin chain was estimated to be
      49 kDa by gel filtration. We have isolated a linkage region hexasaccharide,
      DeltaHexUAalpha1 --> 3GalNAcbeta1 --> 4GlcUAbeta1 --> 3Galbeta1 --> 3Galbeta1 -->
      4Xyl, from this PG by chondroitinase ABC digestion to show that the GAGs in this
      PG are also linked to the core protein through the common tetrasaccharide linker,
      GlcUAbeta1 --> 3Galbeta1 --> 3Galbeta1 --> 4Xyl, found in various PGs. As water
      was not effective in extracting uronic acid-containing glycoconjugates from the
      black nest built by black nest swiftlets (A. maximus), we used 4 M guanidium
      chloride and anion-exchange chromatography in the presence of urea to extract and
      isolate about 30 mg of a chondroitin PG preparation from 10 g of the desialylated
      black nest. As the biological significance of chondroitin is still not well
      understood, bird's nest should become a convenient source for preparing this
      unique GAG to study its biological functions.

PMID- 17035305
TI  - Examination of a fusogenic hexameric core from human metapneumovirus and
      identification of a potent synthetic peptide inhibitor from the heptad repeat 1
      region.
AB  - Paramyxoviruses are a leading cause of childhood illness worldwide. A recently
      discovered paramyxovirus, human metapneumovirus (hMPV), has been studied by our
      group in order to determine the structural relevance of its fusion (F) protein to
      other well-characterized viruses utilizing type I integral membrane proteins as
      fusion aids. Sequence analysis and homology models suggested the presence of
      requisite heptad repeat (HR) regions. Synthetic peptides from HR regions 1 and 2
      (HR-1 and -2, respectively) were induced to form a thermostable (melting
      temperature, approximately 90 degrees C) helical structure consistent in mass
      with a hexameric coiled coil. Inhibitory studies of hMPV HR-1 and -2 indicated
      that the synthetic HR-1 peptide was a significant fusion inhibitor with a 50%
      inhibitory concentration and a 50% effective concentration of approximately 50
      nM. Many viral fusion proteins are type I integral membrane proteins utilizing
      the formation of a hexameric coiled coil of HR peptides as a major driving force
      for fusion. Our studies provide evidence that hMPV also uses a coiled-coil
      structure as a major player in the fusion process. Additionally, viral HR-1
      peptide sequences may need further investigation as potent fusion inhibitors.

PMID- 17035306
TI  - Regulation of CXCL-8 (interleukin-8) induction by double-stranded RNA signaling
      pathways during hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection induces the alpha-chemokine interleukin-8 (CXCL
      8), which is regulated at the levels of transcription and mRNA stability. In the
      current study, CXCL-8 regulation by double-stranded (ds)RNA pathways was analyzed
      in the context of HCV infection. A constitutively active mutant of the retinoic
      acid-inducible gene I (RIG-I), RIG-N, activated CXCL-8 transcription. Promoter
      mutagenesis experiments indicated that NF-kappaB and interferon (IFN)-stimulated
      response element (ISRE) binding sites were required for the RIG-N induction of
      CXCL-8 transcription. IFN-beta promoter stimulator 1 (IPS-1) expression also
      activated CXCL-8 transcription, and mutations of the ISRE and NF-kappaB binding
      sites reduced and abrogated CXCL-8 transcription, respectively. In the presence
      of wild-type RIG-I, transfection of JFH-1 RNA or JFH-1 virus infection of
      Huh7.5.1 cells activated the CXCL-8 promoter. Expression of IFN regulatory factor
      3 (IRF-3) stimulated transcription from both full-length and ISRE-driven CXCL-8
      promoters. Chromatin immunoprecipitation assays demonstrated that IRF-3 and NF
      kappaB bound directly to the CXCL-8 promoter in response to virus infection and
      dsRNA transfection. RIG-N stabilized CXCL-8 mRNA via the AU-rich element in the
      3' untranslated region of CXCL-8 mRNA, leading to an increase in its half-life
      following tumor necrosis factor alpha induction. The data indicate that HCV
      infection triggers dsRNA signaling pathways that induce CXCL-8 via
      transcriptional activation and mRNA stabilization and define a regulatory link
      between innate antiviral and inflammatory cellular responses to virus infection.

PMID- 17035307
TI  - Role for nonstructural protein 1 of severe acute respiratory syndrome coronavirus
      in chemokine dysregulation.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused
      by a novel coronavirus. Since its associated morbidity and mortality have been
      postulated to be due to immune dysregulation, we investigated which of the viral
      proteins is responsible for chemokine overexpression. To delineate the viral and
      cellular factor interactions, the role of four SARS coronavirus proteins,
      including nonstructural protein 1 (nsp-1), nsp-5, envelope, and membrane, were
      examined in terms of cytokine induction. Our results showed that the SARS
      coronavirus nsp-1 plays an important role in CCL5, CXCL10, and CCL3 expression in
      human lung epithelial cells via the activation of NF-kappaB.

PMID- 17035308
TI  - NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's
      sarcoma.
AB  - Kaposi's sarcoma (KS) is an AIDS-defining condition in individuals with human
      immunodeficiency virus type 1 infection. We investigated the phenotype and
      function of the NKG2C+ NK cell population in individuals with AIDS and Kaposi's
      sarcoma. The staging of AIDS KS patients according to the AIDS Clinical Trial
      Group criteria revealed that patients with the S1 disease stage have a
      significantly higher proportion of NKG2C+ cells than those with the S0 disease
      stage. NKG2C+ cells from S1-stage patients are highly enriched for the expression
      of KIR3DL1, are depleted of NKp46, and respond poorly to major histocompatibility
      complex class I-positive target cells. These data demonstrate a link between NK
      cell phenotype and function and disease prognosis in AIDS.

PMID- 17035309
TI  - Nucleocytoplasmic shuttling of bovine papillomavirus E1 helicase downregulates
      viral DNA replication in S phase.
AB  - The papillomavirus E1 protein is essential for the initiation of viral
      replication. We previously showed that the bovine papillomavirus E1 protein is
      unstable and becomes resistant to ubiquitin-mediated degradation when tightly
      bound to cyclin E-cyclin-dependent kinase 2 (Cdk2) before the start of DNA
      synthesis. However, neither the protection nor the targeted degradation of E1
      appears to depend on its phosphorylation by Cdk. Here, we report that Cdk
      phosphorylation of E1 is also not a prerequisite for the initiation of viral DNA
      replication either in vitro or in vivo. Nevertheless, we found that
      phosphorylation of one Cdk site, Ser283, abrogates E1 replicative activity only
      in a cellular context. We show that this site-specific phosphorylation of E1
      drives its export from the nucleus and promotes its continuous nucleocytoplasmic
      shuttling. In addition, we find that E1 shuttling occurs in S phase, when cyclin
      A-Cdk2 is activated. E1 interacts with the active cyclin A-Cdk2 complex and is
      phosphorylated on Ser283 by this kinase. These data suggest that the
      phosphorylation of E1 on Ser283 is a negative regulatory event that is involved
      in preventing the amplification of viral DNA during S phase. This finding reveals
      a novel facet of E1 regulation that could account for the variations of the viral
      replication capacity during different cell cycle phases, as well as in different
      stages of the viral cycle.

PMID- 17035310
TI  - Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells.
AB  - Cell-based hepatitis C virus (HCV) replicon systems have provided a means for
      understanding HCV replication mechanisms and for testing new antiviral agents. We
      describe here a mathematical model of HCV replication that assumes that the
      translation of the HCV polyprotein occurs in the cytoplasm, that HCV RNA
      synthesis occurs in vesicular-membrane structures, and that the strategy of
      replication involves a double-stranded RNA intermediate. Our results shed light
      on the intracellular dynamics of subgenomic HCV RNA replication from transfection
      to steady state within Huh-7 cells. We predict the following: (i) about 6 x 10(3)
      ribosomes are involved in generating millions of HCV NS5B-polymerase molecules in
      a Huh-7 cell, (ii) the observed 10:1 asymmetry of plus- to minus-strand RNA
      levels can be explained by a higher-affinity (200-fold) interaction of HCV NS5B
      polymerase-containing replication complexes with HCV minus-strand RNA over HCV
      plus-strand RNA in order to initiate synthesis, (iii) the latter higher affinity
      can also account for the observed approximately 6:1 plus-strand/minus-strand
      ratio in vesicular-membrane structures, and (iv) the introduction of higher
      numbers of HCV plus-strand RNA by transfection leads to faster attainment of
      steady-state but does not change the steady-state HCV RNA level. Fully permissive
      HCV replication systems have been developed, and the model presented here is a
      first step toward building a comprehensive model for complete HCV replication.
      Moreover, the model can serve as an important tool in understanding HCV
      replication mechanisms and should prove useful in designing and evaluating new
      antivirals against HCV.

PMID- 17035311
TI  - Epstein-barr virus-induced resistance to drugs that activate the mitotic spindle
      assembly checkpoint in Burkitt's lymphoma cells.
AB  - Epstein-Barr virus (EBV) is associated with a number of human cancers, and latent
      EBV gene expression has been reported to interfere with cell cycle checkpoints
      and cell death pathways. Here we show that latent EBV can compromise the mitotic
      spindle assembly checkpoint and rescue Burkitt's lymphoma (BL)-derived cells from
      caspase-dependent cell death initiated in aberrant mitosis. This leads to
      unscheduled mitotic progression, resulting in polyploidy and multi- and/or
      micronucleation. The EBV latent genes responsible for this phenotype are
      expressed from the P3HR1 strain of virus and several viruses with similar genomic
      deletions that remove the EBNA2 gene. Although EBNA2 and the latent membrane
      proteins are not expressed, the EBNA3 proteins are present in these BL cells.
      Survival of the EBV-positive cells is not consistently associated with EBV lytic
      gene expression or with the genes that are expressed in EBV latency I BL cells
      (i.e., EBNA1, EBERs, and BARTs) but correlates with reduced expression of the
      cellular proapoptotic BH3-only protein Bim. These data suggest that a subset of
      latent EBV gene products may increase the likelihood of damaged DNA being
      inherited because of the impaired checkpoint and enhanced survival capacity. This
      could lead to greater genetic diversity in progeny cells and contribute to
      tumorigenesis. Furthermore, since it appears that this restricted latent EBV
      expression interferes with the responses of Burkitt's lymphoma-derived cells to
      cytotoxic drugs, the results of this study may have important therapeutic
      implications in the treatment of some BL.

PMID- 17035312
TI  - Wild-type levels of human immunodeficiency virus type 1 infectivity in the
      absence of cellular emerin protein.
AB  - Preintegration complexes (PICs) mediate retroviral integration, and recent
      results indicate an important role for the inner nuclear membrane protein emerin
      in orienting human immunodeficiency virus type 1 (HIV-1) PICs to chromatin for
      integration. Two other host cell proteins, the barrier-to-autointegration factor
      (BAF) and lamina-associated polypeptide 2alpha (LAP2alpha), seemed to play a
      similar preintegrative role for Moloney murine leukemia virus (MMLV) in addition
      to HIV-1. In contrast, we determined efficient HIV-1 and MMLV infection of HeLa
      P4 cells following potent down-regulation of emerin, BAF, or LAP2alpha protein by
      using short interfering RNA. Mouse embryo fibroblasts ablated for emerin protein
      through gene knockout support the same level of HIV-1 infection as cells derived
      from wild-type littermate control animals. As the expression of human emerin in
      mouse knockout cells fails to affect the level of infectivity achieved in its
      absence, we conclude that HIV-1 efficiently infects cells in the absence of
      emerin protein and, by extension, that emerin is not a universally important
      regulator of HIV-1 infectivity.

PMID- 17035313
TI  - Cytoplasmic residues of herpes simplex virus glycoprotein gE required for
      secondary envelopment and binding of tegument proteins VP22 and UL11 to gE and
      gD.
AB  - The final assembly of herpes simplex virus (HSV) involves binding of tegument
      coated capsids to viral glycoprotein-enriched regions of the trans-Golgi network
      (TGN) as enveloped virions bud into TGN membranes. We previously demonstrated
      that HSV glycoproteins gE/gI and gD, acting in a redundant fashion, are essential
      for this secondary envelopment. To define regions of the cytoplasmic (CT) domain
      of gE required for secondary envelopment, HSVs lacking gD and expressing
      truncated gE molecules were constructed. A central region (amino acids 470 to
      495) of the gE CT domain was important for secondary envelopment, although more C
      terminal residues also contributed. Tandem affinity purification (TAP) proteins
      including fragments of the gE CT domain were used to identify tegument proteins
      VP22 and UL11 as binding partners, and gE CT residues 470 to 495 were important
      in this binding. VP22 and UL11 were precipitated from HSV-infected cells in
      conjunction with full-length gE and gE molecules with more-C-terminal residues of
      the CT domain. gD also bound VP22 and UL11. Expression of VP22 and gD or gE/gI in
      cells by use of adenovirus (Ad) vectors provided evidence that other viral
      proteins were not necessary for tegument/glycoprotein interactions. Substantial
      quantities of VP22 and UL11 bound nonspecifically onto or were precipitated with
      gE and gD molecules lacking all CT sequences, something that is very unlikely in
      vivo. VP16 was precipitated equally whether gE/gI or gD was present in extracts
      or not. These observations illustrated important properties of tegument proteins.
      VP22, UL11, and VP16 are highly prone to binding nonspecifically to other
      proteins, and this did not represent insolubility during our assays. Rather, it
      likely reflects an inherent "stickiness" related to the formation of tegument.
      Nevertheless, assays involving TAP proteins and viral proteins expressed by HSV
      and Ad vectors supported the conclusion that VP22 and UL11 interact specifically
      with the CT domains of gD and gE.

PMID- 17035314
TI  - Evidence of influenza a virus RNA in siberian lake ice.
AB  - Influenza A virus infects a large proportion of the human population annually,
      sometimes leading to the deaths of millions. The biotic cycles of infection are
      well characterized in the literature, including in studies of populations of
      humans, poultry, swine, and migratory waterfowl. However, there are few studies
      of abiotic reservoirs for this virus. Here, we report the preservation of
      influenza A virus genes in ice and water from high-latitude lakes that are
      visited by large numbers of migratory birds. The lakes are along the migratory
      flight paths of birds flying into Asia, North America, Europe, and Africa. The
      data suggest that influenza A virus, deposited as the birds begin their autumn
      migration, can be preserved in lake ice. As birds return in the spring, the ice
      melts, releasing the viruses. Therefore, temporal gene flow is facilitated
      between the viruses shed during the previous year and the viruses newly acquired
      by birds during winter months spent in the south. Above the Arctic Circle, the
      cycles of entrapment in the ice and release by melting can be variable in length,
      because some ice persists for several years, decades, or longer. This type of
      temporal gene flow might be a feature common to viruses that can survive
      entrapment in environmental ice and snow.

PMID- 17035315
TI  - Inhibitory effect of gamma interferon on BK virus gene expression and
      replication.
AB  - BK virus (BKV) is widely accepted to be the causative agent of polyomavirus
      nephropathy. In immunocompromised individuals, especially kidney transplant
      recipients, BKV can replicate in kidney epithelial cells, causing loss of renal
      function and eventual destruction of the graft. Advances in immunosuppressive
      therapies may be partially responsible for the increasing incidence of
      polyomavirus nephropathy among transplant recipients by more effectively
      eliminating components of the immune system, such as gamma interferon (IFN-gamma)
      producing lymphocytes, that keep BKV infections at a subclinical level. In this
      study, we investigated the role of IFN-gamma in regulating lytic infection by
      BKV. Treatment with IFN-gamma inhibited the expression of the viral early protein
      large tumor antigen (TAg) and the late protein VP1 in a dose-dependent manner. We
      detected 1.6- and 12-fold reductions in TAg transcripts at 48 and 96 h
      postinfection, respectively, with 250 U/ml IFN-gamma, suggesting that IFN-gamma
      mediated inhibition occurs at the level of transcription. Furthermore, IFN-gamma
      inhibited the level of viral progeny production as much as 50-fold at a
      multiplicity of infection (MOI) of 0.5 and 80-fold at an MOI of 0.1. The
      inhibitory effects of IFN-gamma were similar for three different strains of BKV
      examined. These results indicate an important role for IFN-gamma in regulating
      BKV lytic infection.

PMID- 17035316
TI  - Linker insertion mutations in the herpes simplex virus type 1 UL28 gene: effects
      on UL28 interaction with UL15 and UL33 and identification of a second-site
      mutation in the UL15 gene that suppresses a lethal UL28 mutation.
AB  - The UL28 protein of herpes simplex virus type 1 (HSV-1) is one of seven viral
      proteins required for the cleavage and packaging of viral DNA. Previous results
      indicated that UL28 interacts with UL15 and UL33 to form a protein complex
      (terminase) that is presumed to cleave concatemeric DNA into genome lengths. In
      order to define the functional domains of UL28 that are important for DNA
      cleavage/packaging, we constructed a series of HSV-1 mutants with linker
      insertion and nonsense mutations in UL28. Insertions that blocked DNA cleavage
      and packaging were found to be located in two regions of UL28: the first between
      amino acids 200 to 400 and the second between amino acids 600 to 740. Insertions
      located in the N terminus or in a region located between amino acids 400 and 600
      did not affect virus replication. Insertions in the carboxyl terminus of the UL28
      protein were found to interfere with the interaction of UL28 with UL33. In
      contrast, all of the UL28 insertion mutants were found to interact with UL15 but
      the interaction was reduced with mutants that failed to react with UL33.
      Together, these observations were consistent with previous conclusions that UL15
      and UL33 interact directly with UL28 but interact only indirectly with each
      other. Revertant viruses that formed plaques on Vero cells were detected for one
      of the lethal UL28 insertion mutants. DNA sequence analysis, in combination with
      genetic complementation assays, demonstrated that a second-site mutation in the
      UL15 gene restored the ability of the revertant to cleave and package viral DNA.
      The isolation of an intergenic suppressor mutant provides direct genetic evidence
      of an association between the UL28 and UL15 proteins and demonstrates that this
      association is essential for DNA cleavage and packaging.

PMID- 17035317
TI  - Antibody recognition and neutralization determinants on domains I and II of West
      Nile Virus envelope protein.
AB  - Previous studies have demonstrated that monoclonal antibodies (MAbs) against an
      epitope on the lateral surface of domain III (DIII) of the West Nile virus (WNV)
      envelope (E) strongly protect against infection in animals. Herein, we observed
      significantly less efficient neutralization by 89 MAbs that recognized domain I
      (DI) or II (DII) of WNV E protein. Moreover, in cells expressing Fc gamma
      receptors, many of the DI- and DII-specific MAbs enhanced infection over a broad
      range of concentrations. Using yeast surface display of E protein variants, we
      identified 25 E protein residues to be critical for recognition by DI- or DII
      specific neutralizing MAbs. These residues cluster into six novel and one
      previously characterized epitope located on the lateral ridge of DI, the linker
      region between DI and DIII, the hinge interface between DI and DII, and the
      lateral ridge, central interface, dimer interface, and fusion loop of DII.
      Approximately 45% of DI-DII-specific MAbs showed reduced binding with mutations
      in the highly conserved fusion loop in DII: 85% of these (34 of 40) cross-reacted
      with the distantly related dengue virus (DENV). In contrast, MAbs that bound the
      other neutralizing epitopes in DI and DII showed no apparent cross-reactivity
      with DENV E protein. Surprisingly, several of the neutralizing epitopes were
      located in solvent-inaccessible positions in the context of the available
      pseudoatomic model of WNV. Nonetheless, DI and DII MAbs protect against WNV
      infection in mice, albeit with lower efficiency than DIII-specific neutralizing
      MAbs.

PMID- 17035318
TI  - Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine
      regimens is enhanced by circumventing vector cross-reactivity.
AB  - The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in
      human populations has led to the development of recombinant adenovirus (rAd)
      vectors derived from rare Ad serotypes as vaccine candidates for human
      immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been
      constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad
      subgroup D, including rAd49. However, the optimal combination of vectors for
      heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive
      vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have
      shown previously that the closely related vectors rAd11 and rAd35 elicited low
      levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs
      correlated with substantial sequence homology in the hexon hypervariable regions
      (HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost
      regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and
      rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent
      with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than
      both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These
      data suggest that optimal heterologous rAd prime-boost regimens should include
      two vectors that are both rare in human populations to circumvent preexisting
      antivector immunity as well as sufficiently immunologically distinct to avoid
      cross-reactive antivector immunity.

PMID- 17035320
TI  - Simian immunodeficiency virus SIVmac239 infection of major histocompatibility
      complex-identical cynomolgus macaques from Mauritius.
AB  - Nonhuman primates are widely used to study correlates of protective immunity in
      AIDS research. Successful cellular immune responses have been difficult to
      identify because heterogeneity within macaque major histocompatibility complex
      (MHC) genes results in quantitative and qualitative differences in immune
      responses. Here we use microsatellite analysis to show that simian
      immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca
      fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC
      genetics, with six common haplotypes accounting for two-thirds of the MHC
      haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques
      carry at least one complete copy of the most frequent MHC haplotype, and 8% of
      these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely
      conserved in unrelated Indian rhesus macaques. After intrarectal infection with
      highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus
      macaques mounted concordant cellular immune responses comparable to those
      previously reported for a pair of monozygotic twins infected with the same strain
      of human immunodeficiency virus. Our identification of relatively abundant SIV
      susceptible, MHC-identical macaques will facilitate research into protective
      cellular immunity.

PMID- 17035319
TI  - Epstein-barr virus latent membrane protein 2B (LMP2B) modulates LMP2A activity.
AB  - Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during
      Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and
      in vivo. LMP2A has important roles in modulating B-cell receptor (BCR) signal
      transduction by associating with the cellular tyrosine kinases Lyn and Syk via
      specific phosphotyrosine motifs found within the LMP2A N-terminal tail domain.
      LMP2A has been shown to alter normal BCR signal transduction in B cells by
      reducing levels of Lyn and by blocking tyrosine phosphorylation and calcium
      mobilization following BCR cross-linking. Although little is currently known
      about the function of LMP2B in B cells, the similarity in structure between LMP2A
      and LMP2B suggests that they may localize to the same cellular compartments. To
      investigate the function of LMP2B, B-cell lines expressing LMP2A, LMP2B,
      LMP2A/LMP2B, and the relevant vector controls were analyzed. As was previously
      shown, cells expressing LMP2A had a dramatic block in normal BCR signal
      transduction as measured by calcium mobilization and tyrosine phosphorylation.
      There was no effect on BCR signal transduction in cells expressing LMP2B.
      Interestingly, when LMP2B was expressed in conjunction with LMP2A, there was a
      restoration of normal BCR signal transduction upon BCR cross-linking. The
      expression of LMP2B did not alter the cellular localization of LMP2A but did bind
      to and prevent the phosphorylation of LMP2A. A restoration of Lyn levels, but not
      a change in LMP2A levels, was also observed in cells coexpressing LMP2B with
      LMP2A. From these results, we conclude that LMP2B modulates LMP2A activity.

PMID- 17035321
TI  - The African swine fever virus nonstructural protein pB602L is required for
      formation of the icosahedral capsid of the virus particle.
AB  - African swine fever virus (ASFV) protein pB602L has been described as a molecular
      chaperone for the correct folding of the major capsid protein p72. We have
      studied the function of protein pB602L during the viral assembly process by using
      a recombinant ASFV, vB602Li, which inducibly expresses the gene coding for this
      protein. We show that protein pB602L is a late nonstructural protein, which, in
      contrast with protein p72, is excluded from the viral factory. Repression of
      protein pB602L synthesis inhibits the proteolytic processing of the two viral
      polyproteins pp220 and pp62 and leads to a decrease in the levels of protein p72
      and a delocalization of the capsid protein pE120R. As shown by electron
      microscopy analysis of cells infected with the recombinant virus vB602Li, the
      viral assembly process is severely altered in the absence of protein pB602L, with
      the generation of aberrant "zipper-like" structures instead of icosahedral virus
      particles. These "zipper-like" structures are similar to those found in cells
      infected under restrictive conditions with the recombinant virus vA72 inducibly
      expressing protein p72. Immunoelectron microscopy studies show that the abnormal
      forms generated in the absence of protein pB602L contain the inner envelope
      protein p17 and the two polyproteins but lack the capsid proteins p72 and pE120R.
      These findings indicate that protein pB602L is essential for the assembly of the
      icosahedral capsid of the virus particle.

PMID- 17035322
TI  - Functional characterization of Kaposi's sarcoma-associated herpesvirus ORF45 by
      bacterial artificial chromosome-based mutagenesis.
AB  - Open reading frame 45 (ORF45) of Kaposi's sarcoma-associated herpesvirus (KSHV)
      encodes an immediate-early protein. This protein is also present in virions as a
      tegument protein. ORF45 protein interacts with interferon regulatory factor 7
      (IRF-7) and inhibits virus-induced type I interferon production by blocking
      activation of IRF-7. To define further the function of ORF45 and the mechanism
      underlying its action, we constructed an ORF45-null recombinant virus genome (BAC
      stop45) by using a bacterial artificial chromosome (BAC) system. Stable 293T
      cells carrying the BAC36 (wild type) and BAC-stop45 genomes were generated. When
      monolayers of 293T BAC36 and 293T BAC-stop45 cells were induced with 12-O
      tetradecanoylphorbol-13-acetate and sodium butyrate, no significant difference
      was found between them in overall viral gene expression and lytic DNA
      replication, but induced 293T BAC-stop45 cells released 10-fold fewer virions to
      the medium than did 293T BAC36 cells. When ORF45-null virus was used to infect
      cells, lower infectivity was observed than for wild-type BAC36. These results
      suggest that KSHV ORF45 plays roles in both early and late stages of viral
      infection, probably in viral ingress and egress.

PMID- 17035323
TI  - CD4+ T-cell responses are required for clearance of West Nile virus from the
      central nervous system.
AB  - Although studies have established that innate and adaptive immune responses are
      important in controlling West Nile virus (WNV) infection, the function of CD4(+)
      T lymphocytes in modulating viral pathogenesis is less well characterized. Using
      a mouse model, we examined the role of CD4(+) T cells in coordinating protection
      against WNV infection. A genetic or acquired deficiency of CD4(+) T cells
      resulted in a protracted WNV infection in the central nervous system (CNS) that
      culminated in uniform lethality by 50 days after infection. Mice surviving past
      day 10 had high-level persistent WNV infection in the CNS compared to wild-type
      mice, even 45 days following infection. The absence of CD4(+) T-cell help did not
      affect the kinetics of WNV infection in the spleen and serum, suggesting a role
      for CD4-independent clearance mechanisms in peripheral tissues. WNV-specific
      immunoglobulin M (IgM) levels were similar to those of wild-type mice in CD4
      deficient mice early during infection but dropped approximately 20-fold at day 15
      postinfection, whereas IgG levels in CD4-deficient mice were approximately 100-
      to 1,000-fold lower than in wild-type mice throughout the course of infection.
      WNV-specific CD8(+) T-cell activation and trafficking to the CNS were unaffected
      by the absence of CD4(+) T cells at day 9 postinfection but were markedly
      compromised at day 15. Our experiments suggest that the dominant protective role
      of CD4(+) T cells during primary WNV infection is to provide help for antibody
      responses and sustain WNV-specific CD8(+) T-cell responses in the CNS that enable
      viral clearance.

PMID- 17035324
TI  - Human immunodeficiency virus type 1 resistance to the small molecule maturation
      inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety
      of single amino acid substitutions at the CA-SP1 cleavage site in Gag.
AB  - The compound 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently and
      specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by
      delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired
      maturation of the viral core. In this study, we investigated HIV-1 resistance to
      DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid
      substitutions in the CA-SP1 cleavage site. Three of the substitutions were lethal
      to HIV-1 replication owing to a deleterious effect on particle assembly. The
      remaining mutants exhibited a range of replication efficiencies; however, each
      mutant was capable of replicating in the presence of concentrations of DSB that
      effectively inhibited wild-type HIV-1. Mutations conferring resistance to DSB
      also led to impaired binding of the compound to immature HIV-1 virions and loss
      of DSB-mediated inhibition of cleavage of Gag. Surprisingly, two of the DSB
      resistant mutants retained an intermediate ability to bind the compound,
      suggesting that binding of DSB to immature HIV-1 particles may not be sufficient
      for antiviral activity. Overall, our results indicate that Gag amino acids L363
      and A364 are critical for inhibition of HIV-1 replication by DSB and suggest that
      these residues form key contacts with the drug in the context of the assembling
      HIV-1 particle. These results have implications for the design of and screening
      for novel inhibitors of HIV-1 maturation.

PMID- 17035325
TI  - Stoichiometry of murine leukemia virus envelope protein-mediated fusion and its
      neutralization.
AB  - Envelope glycoproteins (Envs) of retroviruses form trimers that mediate fusion
      between viral and cellular membranes and are the targets for neutralizing
      antibodies. Understanding in detail how Env trimers mediate membrane fusion, and
      how antibodies interfere with this process, is a fundamental problem in biology
      with practical implications for the development of antiviral drugs and vaccines.
      We investigated the stoichiometry of Env-mediated fusion and its inhibition by
      antibody by inserting an epitope from human immunodeficiency virus for a
      neutralizing antibody (2F5) into the surface (SU) or transmembrane (TM) protein
      of murine leukemia virus Env, along with point mutations that abrogate SU and TM
      function but complement one another. We transfected various combinations of these
      Env genes and investigated Env-mediated cell fusion and its inhibition by 2F5
      antibody. Our results showed that heterotrimers with one functional SU molecule
      were fusion competent in complementation experiments and that one antibody
      molecule was sufficient to inactivate the fusion function of a trimer when its
      epitope was in functional SU or TM. 2F5 antibody could also neutralize trimers
      with the 2F5 epitope in nonfunctional SU or TM, but less efficiently.

PMID- 17035326
TI  - Increased frequency of circulating CCR5+ CD4+ T cells in human immunodeficiency
      virus type 2 infection.
AB  - CCR5 expression determines susceptibility to infection, cell tropism, and the
      rate of human immunodeficiency virus type 1 (HIV-1) disease progression. CCR5 is
      also considered the major HIV-2 coreceptor in vivo, in spite of broad coreceptor
      use in vitro. Here we report a significantly increased proportion of memory
      effector CD4 T cells expressing CCR5 in HIV-2-infected patients correlating with
      CD4 depletion. Moreover, HIV-2 proviral DNA was essentially restricted to memory
      effector CD4, suggesting that this is the main target for HIV-2. Similar levels
      of proviral DNA were found in the two infection categories. Thus, the reduced
      viremia and slow rate of CD4 decline that characterize HIV-2 infection seem to be
      unrelated to coreceptor availability.

PMID- 17035327
TI  - Contribution of T-cell receptor repertoire breadth to the dominance of epitope
      specific CD8+ T-lymphocyte responses.
AB  - Dominant epitope-specific CD8(+) T-lymphocyte responses play a central role in
      controlling viral spread. We explored the basis for the development of this
      focused immune response in simian immunodeficiency virus (SIV)- and simian-human
      immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two
      dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using
      real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vbeta)
      family usage, we show that CD8(+) T-lymphocyte populations specific for dominant
      epitopes are characterized by a diverse Vbeta repertoire, whereas those specific
      for subdominant epitopes employ a dramatically more focused Vbeta repertoire. We
      also demonstrate that dominant epitope-specific CD8(+) T lymphocytes employ TCRs
      with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ
      TCRs with a more restricted CDR3 length. Thus, the relative dominance of an
      epitope-specific CD8(+) T-lymphocyte response reflects the clonal diversity of
      that response. These findings suggest that the limited clonal repertoire of
      subdominant epitope-specific CD8(+) T-lymphocyte populations may limit the
      ability of these epitope-specific T-lymphocyte populations to expand and
      therefore limit the ability of these cell populations to contribute to the
      control of viral replication.

PMID- 17035328
TI  - Prolonged adherence of human immunodeficiency virus-derived vector particles to
      hematopoietic target cells leads to secondary transduction in vitro and in vivo.
AB  - Human immunodeficiency virus type 1-derived lentivirus vectors bearing the
      vesicular stomatitis virus G (VSV-G) envelope glycoprotein demonstrate a wide
      host range and can stably transduce quiescent hematopoietic stem cells. In light
      of concerns about biosafety and potential germ line transmission, they have been
      used predominantly for ex vivo strategies, thought to ensure the removal of
      excess surface-bound particles and prevent in vivo dissemination. Studies
      presented here instead reveal prolonged particle adherence after ex vivo
      exposure, despite serial wash procedures, with subsequent transduction of
      secondary target cells in direct and transwell cocultures. We explored the
      critical parameters affecting particle retention and transfer and show that
      attachment to the cell surface selectively protects virus particles from serum
      complement-mediated inactivation. Moreover, studies with nonmyeloablated murine
      recipients show that transplantation of vector-exposed, washed hematopoietic
      cells results in systemic dissemination of functional VSV-G/lentivector
      particles. We demonstrate genetic marking by inadvertent transfer of vector
      particles and prolonged expression of transgene product in recipient tissues. Our
      findings have implications for biosafety, vector design, and cell biology
      research.

PMID- 17035329
TI  - Characterization of an immunodominant antigenic site on GB virus C glycoprotein
      E2 that is involved in cell binding.
AB  - GB virus type C (GBV-C) is a human flavivirus that may cause persistent
      infection, although most infected individuals clear viremia and develop
      antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and
      cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to
      topologically map immunogenic sites on GBV-C E2 and for the ability to detect or
      block recombinant E2 binding to various cell lines. Five competition groups of
      MAbs were identified. Groups I and II did not compete with each other. Group III
      competed with both groups I and II. Group IV did not compete with group I, II, or
      III. One MAb competed with all of the other MAbs, suggesting that the epitopes
      bound by these MAbs are intimately related. Individually, none of the MAbs
      competed extensively with polyclonal human convalescent antibody (PcAb); however,
      combinations of all five MAb groups completely blocked PcAb binding to E2,
      suggesting that the epitopes bound by these MAbs form a single, immunodominant
      antigenic site. Only group I and III MAbs detected purified recombinant E2 bound
      to cells in binding assays. In contrast, group II MAbs neutralized the binding of
      E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception
      of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the
      peptide included four C-terminal or eight N-terminal residues, suggesting that
      the GBV-C E2 protein contains a single immunodominant antigenic site which
      includes a complex epitope that is involved in specific cellular binding.

PMID- 17035330
TI  - Walleye dermal sarcoma virus retroviral cyclin directly contacts TAF9.
AB  - Walleye dermal sarcoma virus (WDSV) is a complex retrovirus associated with
      dermal sarcomas in walleye fish. A WDSV accessory gene encodes a cyclin homolog
      or retroviral cyclin (rv-cyclin). WDSV rv-cyclin was found to be associated with
      transcription complexes and to affect transcription in a cell-type and promoter
      dependent manner. It inhibited the WDSV promoter in walleye fibroblasts and
      activated transcription from GAL4 promoters when fused to the GAL4 DNA binding
      domain, and an activation domain (AD) has been localized to 30 amino acids in the
      carboxyl region. rv-cyclin can block the pulldown of transcription coactivators
      by the AD of VP16, and the isolated rv-cyclin AD interferes specifically with the
      interaction between the carboxyl halves of the VP16 AD, VP16C, and TATA-binding
      protein-associated factor 9 (TAF9). The carboxyl region and isolated AD can bind
      TAF9 directly in assays of protein-protein interaction in vitro. Furthermore, rv
      cyclin and the isolated rv-cyclin AD interfere specifically with the function of
      VP16C in transcription assays. A previously identified motif within the VP16C
      sequence mediates TAF9 binding, and this motif is present in the activation
      domains of a variety of TAF9-binding transcriptional activators. A similar motif
      is present in the rv-cyclin AD, and point mutations within this motif affect rv
      cyclin function and protein-protein interactions. The results support a model of
      transcription regulation by direct interaction with TAF9.

PMID- 17035331
TI  - Construction and mutagenesis of an artificial bicistronic tick-borne encephalitis
      virus genome reveals an essential function of the second transmembrane region of
      protein e in flavivirus assembly.
AB  - Flaviviruses have a monopartite positive-stranded RNA genome, which serves as the
      sole mRNA for protein translation. Cap-dependent translation produces a
      polyprotein precursor that is co- and posttranslationally processed by proteases
      to yield the final protein products. In this study, using tick-borne encephalitis
      virus (TBEV), we constructed an artificial bicistronic flavivirus genome (TBEV
      bc) in which the capsid protein and the nonstructural proteins were still encoded
      in the cap cistron but the coding region for the surface proteins prM and E was
      moved to a separate translation unit under the control of an internal ribosome
      entry site element inserted into the 3' noncoding region. Mutant TBEV-bc was
      shown to produce particles that packaged the bicistronic RNA genome and were
      infectious for BHK-21 cells and mice. Compared to wild-type controls, however,
      TBEV-bc was less efficient in both RNA replication and infectious particle
      formation. We took advantage of the separate expression of the E protein in this
      system to investigate the role in viral assembly of the second transmembrane
      region of protein E (E-TM2), a second copy of which was retained in the cap
      cistron to fulfill its other role as an internal signal sequence in the
      polyprotein. Deletion analysis and replacement of the entire TBEV E-TM2 region
      with its counterpart from another flavivirus revealed that this element, apart
      from its role as a signal sequence, is important for virion formation.

PMID- 17035332
TI  - NFAT4 is required for JC virus infection of glial cells.
AB  - The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In
      immunosuppressed patients, JCV infection can lead to progressive multifocal
      leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous
      system (CNS). The majority of PML cases occur in the setting of human
      immunodeficiency virus (HIV) infection, and it has been suggested that the link
      between HIV and the development of PML is in part related to the production of
      numerous cytokines in the CNS during HIV infection. To examine the link between
      the expression of inflammatory cytokines and JCV infection, we tested an anti
      inflammatory compound, cyclosporine A (CsA), for its ability to block JCV
      infection of glial cells. We found that CsA inhibited JCV infection by preventing
      the activation of the transcription factor nuclear factor of activated T cells 4
      (NFAT4). Luciferase reporter assays and chromatin immunoprecipitation assays
      revealed that NFAT4 directly bound the JCV promoter during infection and was
      important for the activation of both early and late transcription. In addition,
      the expression of the JCV early viral gene products increased NFAT activity to
      further aid viral transcription. The necessity of NFAT for JCV infection suggests
      that calcium signaling and the activation of NFAT in glial cells are required for
      JCV infection of the CNS.

PMID- 17035333
TI  - Rotavirus nonstructural glycoprotein NSP4 is secreted from the apical surfaces of
      polarized epithelial cells.
AB  - NSP4, a nonstructural glycoprotein encoded by rotavirus, is involved in the
      morphogenesis of virus particles in the endoplasmic reticulum of infected cells.
      NSP4 is also implicated in the pathophysiology of rotavirus-induced diarrhea by
      acting as an enterotoxin. To mediate enterotoxic effects in vivo, NSP4 must be
      secreted or released from rotavirus-infected cells in a soluble form; however,
      previous studies have indicated that NSP4 is a transmembrane glycoprotein
      localized within endomembrane compartments in infected cells. In this study, we
      examined the fate of NSP4 synthesized in Caco-2 cells infected with bovine
      rotavirus. Our studies reveal that NSP4 is actively secreted into the culture
      medium, preferentially from the infected-cell apical surface. The secretion of
      NSP4 is dramatically inhibited by brefeldin A and monensin, suggesting that a
      Golgi-dependent pathway is involved in release of the protein. In agreement with
      the proposed involvement of the Golgi apparatus during secretion, secreted NSP4
      appears to undergo additional posttranslational modification compared to its cell
      associated counterpart and is partially resistant to deglycosylation by
      endoglycosidase H. Our experiments identify a novel, soluble form of NSP4
      secreted from virus-infected cells with the potential to carry out the
      enterotoxigenic role previously attributed to recombinant forms of the protein.

PMID- 17035334
TI  - Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in bovine
      leukemia virus-infected sheep.
AB  - Lymphocyte homeostasis is determined by a critical balance between cell
      proliferation and death, an equilibrium which is deregulated in bovine leukemia
      virus (BLV)-infected sheep. We have previously shown that an excess of
      proliferation occurs in lymphoid tissues and that the peripheral blood population
      is prone to increased cell death. To further understand the mechanisms involved,
      we evaluated the physiological role of the spleen in this accelerated turnover.
      To this end, B lymphocytes were labeled in vivo using a fluorescent marker
      (carboxyfluorescein diacetate succinimidyl ester), and the cell kinetic
      parameters (proliferation and death rates) of animals before and after
      splenectomy were compared. We show that the enhanced cell death observed in BLV
      infected sheep is abrogated after splenectomy, revealing a key role of the spleen
      in B-lymphocyte dynamics.

PMID- 17035336
TI  - Treatment of ischaemic left ventricular dysfunction with milrinone or dobutamine
      administered during coronary artery stenosis in the presence of beta blockade in
      pigs.
AB  - BACKGROUND: This study examines the effects of phosphodiesterase type III
      (PDEIII) inhibition vs beta stimulation on global function of the left ventricle
      (LV) and systemic haemodynamics in a porcine model of acute coronary stenosis
      with beta blockade. METHODS: A total of 18 adult swine were anaesthetized.
      Micromanometer-tipped catheters were placed in the ascending aorta and LV. Two
      pairs of ultrasonic dimension transducers were placed in the subendocardium on
      the short axis proximal to a left anterior descending (LAD) artery occluder and
      the long axis of the LV. Before ischaemia, i.v. esmolol was infused to decrease
      baseline heart rate (HR) by approximately 25%, and all animals received an
      esmolol infusion (150 microg kg(-1) min(-1)). Ischaemia was produced by reducing
      the flow in the LAD artery by approximately 80%, from 17(4) to 3(2) ml min(-1).
      Animals were randomized to receive (after esmolol) one of the following: no drug,
      sham only (Group 1, n=6), control (C); 50 microg kg(-1) i.v. milrinone (Group 2,
      n=6) followed by 0.375 microg kg(-1) min(-1) (M); or incremental doses of
      dobutamine (Group 3, n=6) every 10 min (5, 10 and 20 microg kg(-1) min(-1)) (D).
      Left ventricular function data obtained included HR, arterial and LV pressures,
      cardiac output (CO), Emax and dP/dT. Measurements were taken during five time
      periods: before ischaemia (at baseline, after esmolol) and every 10 min during
      ischaemia (at 10, 20 and 30 min). RESULTS: The effects of beta blockade and
      ischaemia had a significant impact on contractility (Emax) in Group M and
      myocardial performance (left ventricular end-diastolic pressure, LVEDP) in all
      groups. Left ventricular function (Emax, CO, LVEDP and SVR) was better preserved
      when milrinone was added in Group M. A moderate dose of dobutamine (10 microg kg(
      1) min(-1)) increased CO. Only the high dose (20 microg kg(-1) min(-1)) improved
      contractility (Emax), but at the expense of increased SVR. Also, LVEDP with
      either dose of dobutamine remained high and unchanged. CONCLUSIONS: From our
      limited findings, it would appear that there may, theoretically, be some benefit
      for using milrinone in preference to other inotropic drugs in the presence of
      beta blockade. Milrinone administration should be considered in patients with
      acute ischaemic LV dysfunction and preexisting beta blockade before using other
      inotropic drugs such as beta stimulants.

PMID- 17035335
TI  - The betaretrovirus Mason-Pfizer monkey virus selectively excludes simian APOBEC3G
      from virion particles.
AB  - The APOBEC3 protein family can constitute a potent barrier to the successful
      infection of mammalian species by retroviruses. Therefore, any retrovirus that
      has evolved the ability to replicate in a given animal must have developed
      mechanisms that allow it to avoid or inhibit the APOBEC3 proteins expressed in
      that animal. Here, we demonstrate that Mason-Pfizer monkey virus (MPMV) is
      resistant to inhibition by the APOBEC3G protein expressed in its normal host, the
      rhesus macaque, but highly susceptible to inhibition by murine APOBEC3 (mA3).
      MPMV virion particles fail to package rhesus APOBEC3G (rA3G), and MPMV Gag binds
      rA3G poorly in coexpressing cells. In contrast, MPMV virions package mA3
      efficiently and MPMV Gag-mA3 complexes are readily detected. Moreover, mA3, but
      not rA3G, partially colocalizes with MPMV Gag in the cytoplasm of coexpressing
      cells. Previously, we have demonstrated that murine leukemia virus also escapes
      inhibition by APOBEC3 proteins by avoiding virion incorporation of its cognate
      APOBEC3 protein, mA3, yet is inhibited by primate APOBEC3G proteins, which it
      packages effectively (B. P. Doehle, A. Schafer, H. L. Wiegand, H. P. Bogerd, and
      B. R. Cullen, J. Virol. 79:8201-8207, 2005). The finding that two essentially
      unrelated beta- and gammaretroviruses use similar mechanisms to escape inhibition
      by the APOBEC3 proteins found in their normal host species suggests that the
      selective exclusion of APOBEC3 proteins from virion particles may be a general
      mechanism used by simple mammalian retroviruses.

PMID- 17035337
TI  - Spinal fusion surgery in children with non-idiopathic scoliosis: is there a need
      for routine postoperative ventilation?
AB  - BACKGROUND: The perioperative management of children with non-idiopathic
      scoliosis undergoing spinal deformity surgery has not been standardized and the
      current practice is to routinely ventilate these patients in the postoperative
      period. This study reports the experience from a single institution and evaluates
      the need and reasons for postoperative ventilation. Details of ventilated
      patients are presented. METHODS: All patients undergoing spinal fusion surgery
      for non-idiopathic scoliosis were recorded prospectively (2003-4). Patients were
      anaesthetized according to a standardized technique. Physical characteristics,
      cardiopulmonary function, intraoperative blood loss and fluid requirement,
      postoperative need for ventilation and all perioperative adverse events were
      recorded on a computer database. RESULTS: A total of 76.2% of patients were
      safely extubated at the end of surgery without any further complications or need
      for re-ventilation; 23.8% of patients required postoperative ventilation with
      half of the cases being planned before operation and 40% of all patients with
      Duchenne muscular dystrophy (DMD) required postoperative ventilation. There were
      no specific factors that could predict the need for postoperative ventilation,
      although an increased tendency for children with DMD and those with a
      preoperative forced vital capacity <30% towards requiring postoperative
      ventilation was observed. CONCLUSIONS: Early extubation can be safely performed
      after spinal deformity surgery for non-idiopathic scoliosis. The use of short
      acting anaesthetics, drugs to reduce blood loss, experienced spinal anaesthetists
      and the availability of intensive care support are all essential for a good
      outcome in patients with neuromuscular disease and cardiopulmonary co-morbidity.

PMID- 17035338
TI  - Requirement of tumor necrosis factor alpha and nuclear factor-kappaB in the
      induction by IFN-gamma of inducible nitric oxide synthase in macrophages.
AB  - IFN-gamma induces NO production, inducible NO synthase (iNOS) protein, and
      promoter expression in mouse macrophage cells. Mutation of IFN regulatory factor
      1 responsive element, gamma-activated site, as well as NF-kappaB elements in the
      murine iNOS promoter strongly reduced IFN-gamma-induced iNOS transcriptional
      activity. The role of NF-kappaB activation in iNOS induction by IFN-gamma was
      corroborated by overexpression of the NF-kappaB inhibitory protein IkappaBalpha,
      which inhibited iNOS promoter activity induced by IFN-gamma. In addition, IFN
      gamma treatment induced p65 binding to the iNOS promoter by chromatin
      immunoprecipitation assay and NF-kappaB binding to DNA by EMSA, although with a
      delayed kinetics, suggesting an indirect autocrine role for another cytokine
      produced in response to IFN-gamma. It is interesting that we found that IFN-gamma
      induced TNF-alpha secretion, and the induction of iNOS expression by IFN-gamma
      was abolished in primary peritoneal macrophages from TNF-alpha-deficient (TNF
      alpha-/-) mice or in RAW 264.7 cells treated with anti-TNF-alpha neutralizing
      antibodies. Moreover, exogenous addition of recombinant mouse TNF-alpha restored
      iNOS expression induced by IFN-gamma in TNF-alpha-/- mice. It is intriguing that
      NF-kappaB binding to DNA in response to IFN-gamma treatment was absent in TNF
      alpha-/- mice. Taken together, our data suggest that the TNF-alpha produced in
      response to IFN-gamma is required for iNOS induction by activating NF-kappaB
      transcription factor.

PMID- 17035339
TI  - VDR-dependent regulation of mast cell maturation mediated by 1,25
      dihydroxyvitamin D3.
AB  - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that regulates
      bone metabolism, controls calcium homeostasis, and possesses immunomodulatory
      properties. We show here that 1,25(OH)2D3 contributes to the regulation of
      development and function of mast cells, which play a critical role in several
      inflammatory disorders. 1,25(OH)2D3 promotes apoptosis and inhibits maturation of
      mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast
      cell differentiation by 1,25(OH)2D3 is observed at discrete, intermediate stages
      of mast cell development, identified by expression of c-kit, FcepsilonRI, and IL
      3 receptor-alpha chain, and depends on the expression of the vitamin D receptor
      (VDR). It is important that mast cell progenitors obtained from VDR-ablated mice
      undergo an accelerated maturation in vitro and give rise to more responsive mast
      cells than wild-type. Furthermore, histological analysis of mast cell density in
      peripheral tissues reveals a moderate increase in the number of mast cells in the
      skin of VDR-deficient mice compared with wild-type animals. These data support
      the hypothesis of a physiological role of 1,25(OH)2D3 in mast cell development
      and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs.

PMID- 17035340
TI  - The secretion of HMGB1 is required for the migration of maturing dendritic cells.
AB  - Chemokines regulate the migration and the maturation of dendritic cells (DC)
      licensed by microbial constituents. We have recently found that the function of
      DC, including their ability to activate naive, allogeneic CD4+ T cells, requires
      the autocrine/paracrine release of the nuclear protein high mobility group box 1
      (HMGB1). We show here that human myeloid DC, which rapidly secrete upon
      maturation induction their own HMGB1, remodel their actin-based cytoskeleton, up
      regulate the CCR7 and the CXCR4 chemokine receptors, and acquire the ability to
      migrate in response to chemokine receptor ligands. The events are apparently
      causally related: DC challenged with LPS in the presence of HMGB1-specific
      antibodies fail to up-regulate the expression of the CCR7 and CXCR4 receptors and
      to rearrange actin-rich structures. Moreover, DC matured in the presence of anti
      HMGB1 antibodies fail to migrate in response to the CCR7 ligand CCL19 and to the
      CXCR4 ligand CXCL12. The blockade of receptor for advanced glycation end products
      (RAGE), the best-characterized membrane receptor for HMGB1, impinges as well on
      the up-regulation of chemokine receptors and on responsiveness to CCL19 and
      CXCL12. Our data suggest that the autocrine/paracrine release of HMGB1 and the
      integrity of the HMGB1/RAGE pathway are required for the migratory function of
      DC.

PMID- 17035341
TI  - How common are electronic health records in the United States? A summary of the
      evidence.
AB  - Electronic health records (EHRs) are promising tools to improve quality and
      efficiency in health care, but data on their adoption rate are limited. We
      identified surveys on EHR adoption and assessed their quality. Although surveys
      returned widely different estimates of EHR use, when available information is
      limited to studies of high or medium quality, national estimates are possible:
      Through 2005, approximately 23.9 percent of physicians used EHRs in the
      ambulatory setting, while 5 percent of hospitals used computerized physician
      order entry. Large gaps in knowledge, including information about EHR use among
      safety-net providers, pose critical challenges for the development of policies
      aimed at speeding adoption.

PMID- 17035342
TI  - Activity of tigecycline against ESBL-producing and AmpC-hyperproducing
      Enterobacteriaceae from south-east England.

PMID- 17035343
TI  - Maternal illness and drug/medication use during the period surrounding pregnancy
      and risk of childhood leukemia among offspring.
AB  - Maternal illness and drug/medication use (prescription, over-the-counter, and
      illicit) during pregnancy might be related to childhood leukemia risk. These
      issues were evaluated using data (1995-2002) from the Northern California
      Childhood Leukemia Study. The authors selected 365 children under age 15 years
      who had been diagnosed with incident leukemia and birth certificate controls who
      were matched to them on age, sex, Hispanic ethnicity, and maternal race. Data on
      maternal illnesses and drug use from before pregnancy through breastfeeding were
      obtained by interview with the biologic mother and were analyzed by conditional
      logistic regression. Maternal history of influenza/pneumonia was associated with
      a statistically significant increased risk of acute lymphoblastic leukemia (ALL)
      in the offspring (odds ratio (OR) = 1.89, 95% confidence interval (CI): 1.24,
      2.89), although the risk was nonsignificant for common ALL (OR = 1.41, 95% CI:
      0.75, 2.63). A similar pattern of increased risk was found for history of
      sexually transmitted disease. Use of iron supplements was indicative of decreased
      ALL risk (OR = 0.67, 95% CI: 0.47, 0.94). Observing an increased risk of leukemia
      in children of mothers reporting a history of influenza/pneumonia and sexually
      transmitted disease around the time of pregnancy suggests that maternal infection
      might contribute to the etiology of leukemia. Furthermore, maternal iron
      supplement use may be protective against childhood leukemia.

PMID- 17035344
TI  - Cystatin C and measures of physical function in elderly adults: the Health,
      Aging, and Body Composition (HABC) Study.
AB  - Most studies of the relation between kidney function and physical function have
      been conducted in persons with advanced kidney disease and have used creatinine
      based measures of kidney function. Cystatin C concentration is a measure of
      kidney function that is independent of muscle mass, unlike creatinine. Using
      baseline data on 3,043 elderly adults from the Health, Aging, and Body
      Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and
      Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional
      association between cystatin C level and performance on several tests of physical
      function. After adjustment for demographic and lifestyle variables, chronic
      health conditions, and inflammation, each standard-deviation (0.34 mg/liter)
      increase in cystatin C concentration was associated with 1.32 odds (95%
      confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9
      second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09,
      0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83,
      1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension
      strength. In contrast, when kidney function was measured by estimated glomerular
      filtration rate, the association of kidney function with physical function was
      only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements
      in kidney function, as measured by cystatin C concentration, were associated with
      poorer physical function.

PMID- 17035345
TI  - Genetic background influences Th cell differentiation by controlling the capacity
      for IL-2-induced IL-4 production by naive CD4+ T cells.
AB  - Comparative studies using T(h)2-prone BALB/c and T(h)1-prone C57BL/6 mice were
      performed to clarify the influence of genetic background on T(h) cell
      differentiation. The results showed IL-4, the production of which is induced by
      IL-2, to be much more abundantly produced by BALB/c naive CD4(+) T cells than by
      C57BL/6 naive CD4(+) T cells, thereby leading to a tendency for differentiation
      toward T(h)2 in BALB/c naive CD4(+) T cells. This difference in IL-4 production
      between the two naive CD4(+) T cells appeared to be attributable to specific
      intracellular signaling events. Signal transducer and activator of transcription
      5 (STAT5) was preferentially activated by IL-2 in CD4(+) T cells developing in
      BALB/c in contrast to the corresponding cells in C57BL/6. In addition, IL-4 also
      induced stronger STAT5 activation in CD4(+) T cells developing in BALB/c than in
      those developing in C57BL/6, whereas STAT6 was equally activated in these two
      cells. Further results supported the involvement of STAT5 in the difference in
      T(h) cell differentiation between BALB/c and C57BL/6 naive CD4(+) T cells.
      STAT5A(-)(/)(-) naive CD4(+) T cells with the BALB/c genetic background showed
      markedly less IL-2-induced IL-4 production than BALB/c naive CD4(+) T cells.
      Conversely, forced expression of the constitutively active forms of STAT5A and
      STAT5B in C57BL/6 naive CD4(+) T cells promoted the differentiation of T(h)2
      cells. Thus, our results indicate IL-2-induced IL-4 production by naive CD4(+) T
      cells, in which STAT5 activation is involved and directly controlled by the
      genetic background, to influence T(h) cell differentiation in murine strains.

PMID- 17035346
TI  - Efficiency of peptide presentation by dendritic cells compared with other cell
      types: implications for cross-priming.
AB  - Dendritic cells (DCs) play a key role in the induction of cellular immune
      responses by harvesting antigens from peripheral tissue for cross-priming CD8(+)
      T cells. It has been demonstrated that apoptotic bodies, whole- or degraded-cell
      associated or soluble antigens as well as heat shock protein-bound peptides can
      be taken up, processed and cross-presented by DCs. Since cells are continuously
      releasing peptides from their surface MHC molecules, DCs in the tissues are
      exposed to such peptides and might process and present them to T cells as an
      additional pathway for cross-priming. To investigate this possibility, we
      compared and characterized the presentation of exogenous peptides by DCs and
      other cell types employing novel recombinant antibodies with TCR-like
      specificities for specific peptide-MHC complexes (pMHCs). These analyses reveal
      that loading of immature and mature DCs with peptide is far less efficient than
      it is for monocytes, T and B lymphocytes, B-lymphoblastoid, melanoma and TAP
      deficient T2 cells. This inefficiency of peptide transfer to the MHC molecules of
      DCs makes it unlikely that these cells recycle peptides released from the MHC
      molecules of other cells and may explain why cross-presentation of such peptides
      has not yet been observed.

PMID- 17035347
TI  - Roles of the small intestine for induction of toll-like receptor 4-mediated
      innate resistance in naturally acquired murine toxoplasmosis.
AB  - Peroral infection of Toxoplasma gondii is thought to reflect the typical
      infection route of naturally acquired toxoplasmosis in humans. We have
      investigated possible differential roles of toll-like receptor 2 (TLR2) and TLR4
      in host defense against naturally acquired murine toxoplasmosis. After peroral
      inoculation of T. gondii ME49 cysts, TLR4-deficient C3H/HeJ mice were more
      susceptible to infection than wild-type (WT) C3H/HeN mice, as shown by increased
      cyst number and low production of cytokines, which are the key factors in
      protective immunity. When mice were inoculated by intra-peritoneal inoculation of
      T. gondii, there were no significant differences in the number of brain cysts and
      cytokine productions between C3H/HeJ and C3H/HeN mice. Histopathologic
      examination revealed severe inflammation in the small intestine of C3H/HeJ (TLR4
      deficient) mice, while an increased number of TLR4-positive mononuclear cells was
      found in C3H/HeN (WT) mice. To confirm these phenomena, TLR2(-/-) or TLR4(-/-)
      mice were infected perorally with T. gondii cysts. TLR4(-/-) mice were more
      susceptible to infection compared with TLR2(-/-) and C57BL/6 mice. Nuclear factor
      kappa B activation through TLR4 agonistic activity of T. gondii ME49 was
      demonstrated by luciferase assay using stably expressing mouse (m) TLR2 or
      mTLR4/mMD-2 transfectants. We demonstrate here for the first time that innate
      immune recognition by TLR4 is involved in protective mechanisms against peroral
      infection with T. gondii ME49. These results suggest that the small intestine
      plays an important role in the induction of innate immunity in naturally acquired
      toxoplasmosis.

PMID- 17035348
TI  - Differential induction of Th1-prone immunity by human dendritic cells activated
      with Sporothrix schenckii of cutaneous and visceral origins to determine their
      different virulence.
AB  - Sporotrichosis is caused by a thermo-dependent dimorphic fungus, Sporothrix
      schenckii. The major clinical manifestations occur in the skin; however, cases of
      visceral manifestations have also been increasingly reported with some being
      observed in immune compromised patients. Different virulence of individual S.
      schenckii strain as well as immune status of the host could contribute to form
      such different clinical manifestations. Thus, the purpose of the study was to
      investigate whether different virulence of individual S. schenckii could be a
      factor for such clinical difference. We investigated the interactions between
      human monocyte-derived dendritic cells (MoDCs) and S. schenckii, assessed by (i)
      morphological features, (ii) surface marker expressions, cytokine productions,
      (iii) signaling pathways and (iv) allostimulatory activity of the activated
      MoDCs. Immature MoDCs, obtained from peripheral blood monocytes supplemented with
      granulocyte macrophage colony-stimulating factor and IL-4, were stimulated with
      S. schenckii strains of both yeasts and conidia forms of different origins
      (cutaneous isolates: KMU4649, IFM5906 and IFM46010; visceral isolates: KMU4648,
      IFM41598 and ATCC26331) to be used for various assays. Through the analysis, we
      found that the cutaneous S. shenckii of cutaneous origins were more potent to
      activate MoDCs to induce strong T(h)1 response, as evidenced by abundant IFN
      gamma production, while the S. shenckii of visceral origins induced only minimal
      dendritic cell activation and T(h)1 induction. The p38 mitogen-activated protein
      kinase and c-Jun N-terminal kinase signaling pathways appeared to be associated
      with the differential activation of the MoDCs by S. schenckii of cutaneous and
      the visceral origins. Overall, we concluded that the differential activation of
      MoDCs by S. schenckii of cutaneous and visceral origins to induce T(h)1 response,
      other than immune status or the host, may be a factor for their different
      clinical manifestations.

PMID- 17035349
TI  - Diversity in lectins enables immune recognition and differentiation of wide
      spectrum of pathogens.
AB  - Carbohydrate-binding lectins play essential roles as pattern recognition
      receptors in innate immunity in both vertebrates and invertebrates. The
      carcinolectins 5 (CL5a and CL5b, the CL5 isoforms of horseshoe crab,
      Carcinoscorpius rotundicauda, with apparent sizes of 36 and 40 kDa, respectively)
      are prominent plasma lectins that bind all representative microbes and pathogen
      associated molecular pattern molecules. Different cDNA isoforms of both CL5a and
      CL5b were isolated, leading to our speculation on their functional divergence.
      Characterization of CL5 isoforms bound to microbial cell surfaces demonstrates
      the diversity of these lectins. The resolution patterns of the isoforms that
      associate with fungus differ from those that associate with bacteria, suggesting
      the unique roles these lectins play in the recognition and differentiation of
      microbes. We postulate that different populations of plasma lectins act in
      collaboration in frontline innate immune defense against disparate pathogens. The
      functional diversity of lectins in invertebrates appears to evolutionarily
      compensate for the lack of acquired immunity.

PMID- 17035350
TI  - An invertebrate TNF functional analogue activates macrophages via lectin
      saccharide interaction with ion channels.
AB  - The invertebrate pattern-recognition protein named coelomic cytolytic factor
      (CCF) and the mammalian cytokine tumor necrosis factor (TNF) share functional
      analogies that are based on a similar saccharide recognition specificity. In
      particular, CCF and TNF have been shown to interact with ion channels on the
      surface of vertebrate cells via N,N'-diacetylchitobiose lectin-like activity. In
      the present study, we show that CCF-induced membrane depolarization results in
      the release of TNF, IL-6 and nitric oxide (NO) by macrophages via nuclear factor
      kappaB signaling. Interestingly, our data suggest that TNF contributes, through
      lectin-saccharide interaction, to the secretion of IL-6 and NO induced by CCF.
      This experimental non-physiological setting based on the interaction of an
      invertebrate defense lectin with vertebrate cells involved in the innate immune
      response may have highlighted an evolutionarily ancient mechanism of macrophage
      activation in vertebrates.

PMID- 17035351
TI  - School-based health education campaign--a potential tool for social mobilization
      to promote the use of DEC-fortified salt towards elimination of lymphatic
      filariasis.
AB  - Community compliance is crucial for the success of mass treatment using cooking
      salt fortified with diethylcarbamazine citrate (DEC) for the elimination of
      lymphatic filariasis (LF). We describe the role and effectiveness of school-based
      health education for social mobilization to promote the use of DEC salt, in an
      endemic district in India. Health education through classroom sessions was the
      main motivational strategy used. Community members were targeted to receive the
      message through children. The impact of this approach was assessed among students
      and community members using an interviewer-administered questionnaire and
      analysis of salt samples for DEC content from households. Significant improvement
      in awareness on LF among students and community respondents was observed. School
      health education (SHE) could promote the use of DEC salt by 19% points more in
      households with children in schools covered under health education campaign
      [campaign school (CS)] compared with others. Significantly higher proportion
      (72.7%) of samples from households with children in CS had detectable DEC,
      indicating the impact of the intervention on enhancing the use of DEC salt by the
      community. The results exemplify that SHE is a potential tool for improving and
      sustaining compliance, thus serving as part of a public health strategy to
      eliminate LF using DEC salt.

PMID- 17035352
TI  - Evaluating the properties of a stage-specific self-efficacy scale for physical
      activity using classical test theory, confirmatory factor analysis and item
      response modeling.
AB  - The purpose of this paper was to evaluate the psychometric properties of a stage
      specific self-efficacy scale for physical activity with classical test theory
      (CTT), confirmatory factor analysis (CFA) and item response modeling (IRM). Women
      who enrolled in the Women On The Move study completed a 20-item stage-specific
      self-efficacy scale developed for this study [n=226, 51.1% African-American and
      48.9% Hispanic women, mean age = 49.2 (+/-7.0) years, mean body mass index = 29.7
      (+/-6.4)]. Three analyses were conducted: (i) a CTT item analysis, (ii) a CFA to
      validate the factor structure and (iii) an IRM analysis. The CTT item analysis
      and the CFA results showed that the scale had high internal consistency (ranging
      from 0.76 to 0.93) and a strong factor structure. Results also showed that the
      scale could be improved by modifying or eliminating some of the existing items
      without significantly altering the content of the scale. The IRM results also
      showed that the scale had few items that targeted high self-efficacy and the
      stage-specific assumption underlying the scale was rejected. In addition, the IRM
      analyses found that the five-point response format functioned more like a four
      point response format. Overall, employing multiple methods to assess the
      psychometric properties of the stage-specific self-efficacy scale demonstrated
      the complimentary nature of these methods and it highlighted the strengths and
      weaknesses of this scale.

PMID- 17035354
TI  - Rate and polarity of gene fusion and fission in Oryza sativa and Arabidopsis
      thaliana.
AB  - Eukaryotic gene fusion and fission events are mechanistically more complicated
      than in prokaryotes, and their quantitative contributions to genome evolution are
      still poorly understood. We have identified all differentially composite or split
      genes in 2 fully sequenced plant genomes, Oryza sativa and Arabidopsis thaliana.
      Out of 10,172 orthologous gene pairs, 60 (0.6% of the total) revealed a verified
      fusion or fission event in either lineage after the divergence of O. sativa and
      A. thaliana. Polarizing these events by outgroup comparison revealed differences
      in the rate of gene fission but not of gene fusion in the rice and Arabidopsis
      lineages. Gene fission occurred at a higher rate than gene fusion in the O.
      sativa lineage and was furthermore more common in rice than in Arabidopsis.
      Nucleotide insertion bias has promoted gene fission in the O. sativa lineage,
      consistent with its generally longer nucleotide sequences than A. thaliana in
      selectively neutral regions, and with the abundance of transposable elements in
      rice. The divergence time of monocots and dicots (140-200 Myr) indicates that
      gene fusion/fission events occur at an average rate of 1x10(-11) to 2x10(-11)
      events per gene per year, approximately 100-fold slower than the average per site
      nuclear nucleotide substitution rate in these lineages. Gene fusion and fission
      are thus rare and slow processes in higher plant genomes; they should be of
      utility to address deeper evolutionary relationships among plants--and the
      relationship of plants to other eukaryotic lineages--where sequence-based
      phylogenies provide equivocal or conflicting results.

PMID- 17035353
TI  - Evolution of the Rho family of ras-like GTPases in eukaryotes.
AB  - GTPases of the Rho family are molecular switches that play important roles in
      converting and amplifying external signals into cellular effects. Originally
      demonstrated to control the dynamics of the F-actin cytoskeleton, Rho GTPases
      have been implicated in many basic cellular processes that influence cell
      proliferation, differentiation, motility, adhesion, survival, or secretion. To
      elucidate the evolutionary history of the Rho family, we have analyzed over 20
      species covering major eukaryotic clades from unicellular organisms to mammals,
      including platypus and opossum, and have reconstructed the ontogeny and the
      chronology of emergence of the different subfamilies. Our data establish that the
      20 mammalian Rho members are structured into 8 subfamilies, among which Rac is
      the founder of the whole family. Rho, Cdc42, RhoUV, and RhoBTB subfamilies
      appeared before Coelomates and RhoJQ, Cdc42 isoforms, RhoDF, and Rnd emerged in
      chordates. In vertebrates, gene duplications and retrotranspositions increased
      the size of each chordate Rho subfamily, whereas RhoH, the last subfamily, arose
      probably by horizontal gene transfer. Rac1b, a Rac1 isoform generated by
      alternative splicing, emerged in amniotes, and RhoD, only in therians. Analysis
      of Rho mRNA expression patterns in mouse tissues shows that recent subfamilies
      have tissue-specific and low-level expression that supports their implication
      only in narrow time windows or in differentiated metabolic functions. These
      findings give a comprehensive view of the evolutionary canvas of the Rho family
      and provide guides for future structure and evolution studies of other components
      of Rho signaling pathways, in particular regulators of the RhoGEF family.

PMID- 17035355
TI  - Impact of early lifetime trauma in later life: depression among Holocaust
      survivors 60 years after the liberation of Auschwitz.
AB  - RATIONALE: Holocaust survivors, who experienced trauma 60 years ago, provide an
      opportunity to explore the impact of early lifetime trauma in later life and, in
      particular, the interplay of depression and posttraumatic stress disorder (PTSD).
      In this study, the authors contrast depressed Holocaust survivors (HD),
      nondepressed Holocaust survivors (HND), and older depressed persons (CD).
      METHODS: The sample consisted of 36 consecutive Holocaust survivors (mean age: 79
      years) treated in a primary care practice, among whom 20 (56%) were diagnosed as
      having a major depressive disorder and 16 as nondepressed; 18 depressed non
      Holocaust Jewish primary care patients served as controls (mean age: 84 years).
      The authors examined nine clinical and social variables. The Kruskal-Wallis, Mann
      Whitney U, and chi(2) tests were used to contrast the groups. The authors used a
      conservative significance level of .01. RESULTS: In contrast to the CD group, the
      HD group was significantly older, more likely to report PTSD and guilt symptoms,
      to have higher Beck Anxiety Inventory (BAI) and Brief Psychiatric Rating Scale
      (BPRS) scores, and to have more impaired social functioning. In contrast to the
      HND group, the HD group was significantly more likely to report PTSD and guilt
      feelings, to have higher Hamilton Depression Scale (HAM-D), BAI, and BPRS scores,
      and to have more impaired social functioning. In contrast to the CD group, the
      HND group was significantly more likely to have PTSD symptoms and to have lower
      HAM-D and BPRS scores. CONCLUSIONS: The prevalence of depression and PTSD
      symptoms were very high among survivors. Depressed survivors had significantly
      worse psychologic and social functioning than depressed controls. Depressed
      survivors had more PTSD symptoms than nondepressed survivors, although it is
      unclear as to the causal direction of the relationship between depression and
      PTSD.

PMID- 17035356
TI  - Risk and protective factors for psychopathology among older versus younger adults
      after the 2004 Florida hurricanes.
AB  - OBJECTIVE: Previous research demonstrates increased resiliency to psychopathology
      after disasters among older adults. However, little is known about differences in
      age-based risk and protective factors for postdisaster mental illness. METHOD:
      The authors used random-digit dialing methodology to survey 1,130 older adults
      (60+ years) and 413 younger adults residing in Florida counties directly affected
      by the 2004 hurricanes. Assessed risk and protective factors included
      demographics, social support, displacement, incurred dollar losses, perceived
      positive outcomes, and self-rated health status. Outcome variables included
      symptom counts of Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition-defined posttraumatic stress disorder (PTSD), major depressive disorder
      (MDD), and generalized anxiety disorder (GAD). RESULTS: Older adults reported
      fewer symptoms of PTSD, MDD, and GAD. Explanatory risk variables accounted for
      large proportions of variance, but differed in meaningful ways across age groups.
      CONCLUSION: Although older adults are less symptomatic, their psychologic
      reactions appear more closely connected to economic consequences of disasters.

PMID- 17035357
TI  - The coccolithovirus microarray: an array of uses.
AB  - The Coccolithoviridae is a recently discovered family of giant algal viruses.
      Here, we review the genomic and transcriptomic characterization of this family
      based on the results generated from a coccolithovirus microarray. The microarray
      has been used to aid the annotation of the genome, to investigate the infection
      process at the transcriptional level and to assess the diversity in genomic
      content within the family.

PMID- 17035358
TI  - The Consortium on the Genetics of Endophenotypes in Schizophrenia: model
      recruitment, assessment, and endophenotyping methods for a multisite
      collaboration.
AB  - BACKGROUND: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing,
      National Institute of Mental Health-funded, 7-site collaboration investigating
      the occurrence and genetic architecture of quantitative endophenotypes related to
      schizophrenia. The purpose of this article is to provide a description of the
      COGS structure and methods, including participant recruitment and assessment.
      METHODS: The hypothesis-driven recruitment strategy ascertains families that
      include a proband with a Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition diagnosis of schizophrenia, and at least one unaffected full
      sibling available for genotyping and endophenotyping, along with parents
      available for genotyping and (optional depending on age) endophenotyping. The
      family structure is selected to provide contrast in quantitative endophenotypic
      traits and thus to maximize the power of the planned genetic analyses. Probands
      are recruited from many sources including clinician referrals, local National
      Alliance for the Mentally Ill chapters, and advertising via the media. All
      participants undergo a standardized protocol that includes clinical
      characterization, a blood draw for genotyping, and endophenotype assessments (P50
      suppression, prepulse inhibition, antisaccade performance, continuous performance
      tasks, letter-number span, verbal memory, and a computerized neurocognitive
      battery). Investigators participate in weekly teleconferences to coordinate and
      evaluate recruitment, clinical assessment, endophenotyping, and continuous
      quality control of data gathering and analyses. Data integrity is maintained
      through use of a highly quality-assured, centralized web-based database. RESULTS:
      As of February 2006, 355 families have been enrolled and 688 participants have
      been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44),
      first-degree biological relatives (n = 343, M:F = 151:192), and community
      comparison subjects (n = 191, M:F = 81:110). DISCUSSION: Successful multisite
      genetics collaborations must institute standardized methodological criteria for
      assessment and recruitment that are clearly defined, well communicated, and
      uniformly applied. In parallel, studies utilizing endophenotypes require strict
      adherence to criteria for cross-site data acquisition, equipment calibration and
      testing and software equivalence, and continuous quality assurance for many
      measures obtained across sites. This report describes methods and presents the
      structure of the COGS as a model of multisite endophenotype genetic studies. It
      also provides demographic information after the first 2 years of data collection
      on a sample for whom the behavioral data and genetics of endophenotype
      performance will be fully characterized in future articles. Some issues discussed
      in the reviews that follow reflect the challenges of evaluating endophenotypes in
      studies of the genetic architecture of endophenotypes in schizophrenia.

PMID- 17035359
TI  - Statistical genetics concepts and approaches in schizophrenia and related
      neuropsychiatric research.
AB  - Statistical genetics is a research field that focuses on mathematical models and
      statistical inference methodologies that relate genetic variations (ie, naturally
      occurring human DNA sequence variations or "polymorphisms") to particular traits
      or diseases (phenotypes) usually from data collected on large samples of families
      or individuals. The ultimate goal of such analysis is the identification of genes
      and genetic variations that influence disease susceptibility. Although of extreme
      interest and importance, the fact that many genes and environmental factors
      contribute to neuropsychiatric diseases of public health importance (eg,
      schizophrenia, bipolar disorder, and depression) complicates relevant studies and
      suggests that very sophisticated mathematical and statistical modeling may be
      required. In addition, large-scale contemporary human DNA sequencing and related
      projects, such as the Human Genome Project and the International HapMap Project,
      as well as the development of high-throughput DNA sequencing and genotyping
      technologies have provided statistical geneticists with a great deal of very
      relevant and appropriate information and resources. Unfortunately, the use of
      these resources and their interpretation are not straightforward when applied to
      complex, multifactorial diseases such as schizophrenia. In this brief and largely
      nonmathematical review of the field of statistical genetics, we describe many of
      the main concepts, definitions, and issues that motivate contemporary research.
      We also provide a discussion of the most pressing contemporary problems that
      demand further research if progress is to be made in the identification of genes
      and genetic variations that predispose to complex neuropsychiatric diseases.

PMID- 17035360
TI  - Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in
      visual cortex and hippocampus.
AB  - Various forms of synaptic plasticity, including spike timing-dependent
      plasticity, can be accounted for by calcium-dependent models of synaptic
      plasticity. However, recent results in which synaptic plasticity is induced by
      multi-spike protocols cannot simply be accounted for by linear superposition of
      plasticity due to spike pairs or by existing calcium-dependent models. In this
      paper, we show that multi-spike protocols can be accounted for if, in addition to
      the dynamics of back-propagating action potentials, stochastic synaptic dynamics
      are taken into account. We show that a stochastic implementation can account for
      the data better than a deterministic implementation and is also more robust. Our
      results demonstrate that differences between experimental results obtained in
      hippocampus and visual cortex can be accounted for by the different synaptic and
      dendritic dynamics in these two systems.

PMID- 17035361
TI  - Partial reconstruction of muscle activity from a pruned network of diverse motor
      cortex neurons.
AB  - Primary motor cortex (M1) neurons traditionally have been viewed as "upper motor
      neurons" that directly drive spinal motoneuron pools, particularly during finger
      movements. We used spike-triggered averages (SpikeTAs) of electromyographic (EMG)
      activity to select M1 neurons whose spikes signaled the arrival of input in
      motoneuron pools, and examined the degree of similarity between the activity
      patterns of these M1 neurons and their target muscles during 12 individuated
      finger and wrist movements. Neuron-EMG similarity generally was low. Similarity
      was unrelated to the strength of the SpikeTA effect, to whether the effect was
      pure versus synchrony, or to the number of muscles influenced by the neuron.
      Nevertheless, the sum of M1 neuron activity patterns, each weighted by the sign
      and strength of its SpikeTA effect, could be more similar to the EMG than the
      average similarity of individual neurons. Significant correlations between the
      weighted sum of M1 neuron activity patterns and EMG were obtained in six of 17
      muscles, but showed R(2) values ranging from only 0.26 to 0.42. These
      observations suggest that additional factors-including inputs from sources other
      than M1 and nonlinear summation of inputs to motoneuron pools-also contributed
      substantially to EMG activity patterns. Furthermore, although each of these M1
      neurons produced SpikeTA effects with a significant peak or trough 6-16 ms after
      the triggering spike, shifting the weighted sum of neuron activity to lead the
      EMG by 40-60 ms increased their similarity, suggesting that the influence of M1
      neurons that produce SpikeTA effects includes substantial synaptic integration
      that in part may reach the motoneuron pools over less-direct pathways.

PMID- 17035362
TI  - Duration-dependent response of SI to vibrotactile stimulation in squirrel monkey.
AB  - In previous studies, we showed that the spatial and intensive aspects of the SI
      response to skin flutter stimulation are modified systematically as stimulus
      amplitude is increased. In this study, we examined the effects of duration of
      skin flutter stimulation on the spatiotemporal characteristics of the response of
      SI cortex. Optical intrinsic signal (OIS) imaging was used to study the evoked
      response in SI of anesthetized squirrel monkeys to 25-Hz sinusoidal vertical skin
      displacement stimulation. Four stimulus durations were tested (0.5, 1.0, 2.0, and
      5.0 s); all stimuli were delivered to a discrete site on the glabrous skin of the
      contralateral forelimb. Skin stimulation evoked a prominent increase in
      absorbance within the forelimb regions in SI of the contralateral hemisphere.
      Responses to brief (0.5 s) stimuli were weaker and spatially more extensive than
      responses to longer duration stimuli (1.0, 2.0, and 5.0 s). Stimuli >or=1 s in
      duration suppressed responses to below background levels (decreased absorbance)
      in regions that surrounded the maximally activated region. The magnitude of the
      suppression in the surrounding regions was nonuniform and usually was strongest
      medial and posterior to the maximally activated region. The results show that
      sustained (>or=1.0 s) stimulation decreases the spatial extent of the responding
      SI cortical population. Registration of the optical responses with the previously
      documented SI topographical organization strongly suggests that the cortical
      regions that undergo the strongest suppression represent skin sites that are
      normally co-stimulated during tactile exploration.

PMID- 17035363
TI  - 7-12 Hz high-voltage rhythmic spike discharges in rats evaluated by antiepileptic
      drugs and flicker stimulation.
AB  - Paroxysmal 7- to 12-Hz high-voltage rhythmic spike (HVRS) or spike-wave
      discharges often appear in several particular strains of rats. However,
      functional hypotheses of these 7-12 Hz high-voltage cortical oscillations
      (absence seizure vs. idling mu rhythm) are inconclusive. The mu rhythm can be
      provoked by flicker stimulation (FS) in most people, but FS is less effective at
      eliciting absence epileptic activity. Therefore FS and antiepileptic drugs were
      used to verify the role of HVRS activity in Long-Evans rats with spontaneous HVRS
      discharges and Wistar rats without spontaneous HVRS discharges. The occurrence of
      HVRS discharges was significantly reduced by antiabsence drugs (ethosuximide,
      valproic acid, and diazepam) in dose-dependent manners, but high-dose
      carbamazepine displayed little effect. On the other hand, oscillation frequencies
      and durations of spontaneous HVRS discharges were not altered by FS. Under
      asynchronous brain activity, many FSs (>60%) elicited small-amplitude mu-rhythm
      like activity in the barrel cortex concomitant with FS-related rhythms in the
      occipital cortex and resulted in significant augmentation of 7-12 Hz power in the
      parietal region. Furthermore, a large portion of FSs (>60%) revealed increase of
      7-12 Hz power of the parietal cortex after ethosuximide administration (100 mg/kg
      ip) in Long-Evans rats. Similar FS-elicited phenomena also appeared in Wistar
      rats. Characteristics of FS-elicited mu-rhythm-like activities were consistent
      with those observed in humans, and they remarkably differed from those of
      spontaneous HVRS discharges. These results support the hypothesis that HVRS
      activity in Long-Evans rats may be an absence-like seizure activity rather than
      the mu rhythm.

PMID- 17035364
TI  - Persistent enhancement of neuron-glia signaling mediated by increased
      extracellular K+ accompanying long-term synaptic potentiation.
AB  - Neuron-glia signaling is important for neural development and functions. This
      signaling may be regulated by neuronal activity and undergo modification similar
      to long-term potentiation (LTP) of neuronal synapses, a hallmark of neuronal
      plasticity. We found that tetanic stimulation of Schaffer collaterals (Sc) in the
      hippocampus that induced LTP in neurons also resulted in LTP-like persistent
      elevation of Sc-evoked slow depolarization in perisynaptic astrocytes. The
      elevated slow depolarization in astrocytes was abolished by NMDA receptor
      antagonist and K(+) channel inhibitors, but not by Ca(2+) chelator BAPTA loaded
      in the recorded astrocytes, suggesting involvement of an increased extracellular
      K(+) accumulation accompanying LTP of neuronal synapses. The increased K(+)
      accumulation and astrocyte depolarization after LTP induction may reduce the
      efficiency of glial glutamate transporters, which may contribute to the enhanced
      synaptic efficacy. The neuronal activity-induced persistent enhancement of neuron
      glia signaling may thus have important physiological relevance.

PMID- 17035365
TI  - Acutely dissociated sensory neurons: normal or neuropathic? Focus on:
      "Dissociation of dorsal root ganglion neurons induces hyperexcitability that is
      maintained by increased responsiveness to cAMP and cGMP".

PMID- 17035367
TI  - Sound localization during homotopic and heterotopic bilateral cooling
      deactivation of primary and nonprimary auditory cortical areas in the cat.
AB  - Although the contributions of primary auditory cortex (AI) to sound localization
      have been extensively studied in a large number of mammals, little is known of
      the contributions of nonprimary auditory cortex to sound localization. Therefore
      the purpose of this study was to examine the contributions of both primary and
      all the recognized regions of acoustically responsive nonprimary auditory cortex
      to sound localization during both bilateral and unilateral reversible
      deactivation. The cats learned to make an orienting response (head movement and
      approach) to a 100-ms broad-band noise stimulus emitted from a central speaker or
      one of 12 peripheral sites (located in front of the animal, from left 90 degrees
      to right 90 degrees , at 15 degrees intervals) along the horizontal plane after
      attending to a central visual stimulus. Twenty-one cats had one or two bilateral
      pairs of cryoloops chronically implanted over one of ten regions of auditory
      cortex. We examined AI [which included the dorsal zone (DZ)], the three other
      tonotopic fields [anterior auditory field (AAF), posterior auditory field (PAF),
      ventral posterior auditory field (VPAF)], as well as six nontonotopic regions
      that included second auditory cortex (AII), the anterior ectosylvian sulcus
      (AES), the insular (IN) region, the temporal (T) region [which included the
      ventral auditory field (VAF)], the dorsal posterior ectosylvian (dPE) gyrus
      [which included the intermediate posterior ectosylvian (iPE) gyrus], and the
      ventral posterior ectosylvian (vPE) gyrus. In accord with earlier studies,
      unilateral deactivation of AI/DZ caused sound localization deficits in the
      contralateral field. Bilateral deactivation of AI/DZ resulted in bilateral sound
      localization deficits throughout the 180 degrees field examined. Of the three
      other tonotopically organized fields, only deactivation of PAF resulted in sound
      localization deficits. These deficits were virtually identical to the unilateral
      and bilateral deactivation results obtained during AI/DZ deactivation. Of the six
      nontonotopic regions examined, only deactivation of AES resulted in sound
      localization deficits in the contralateral hemifield during unilateral
      deactivation. Although bilateral deactivation of AI/DZ, PAF, or AES resulted in
      profound sound localization deficits throughout the entire field, the cats were
      generally able to orient toward the hemifield that contained the acoustic
      stimulus, but not accurately identify the location of the stimulus. Neither
      unilateral nor bilateral deactivation of areas AAF, VPAF, AII, IN, T, dPE, nor
      vPE had any effect on the sound localization task. Finally, bilateral heterotopic
      deactivations of AI/DZ, PAF, or AES yielded deficits that were as profound as
      bilateral homotopic cooling of any of these sites. The fact that deactivation of
      any one region (AI/DZ, PAF, or AES) was sufficient to produce a deficit indicated
      that normal function of all three regions was necessary for normal sound
      localization. Neither unilateral nor bilateral deactivation of AI/DZ, PAF, or AES
      affected the accurate localization of a visual target. The results suggest that
      hemispheric deactivations contribute independently to sound localization
      deficits.

PMID- 17035366
TI  - Complementary postsynaptic activity patterns elicited in olfactory bulb by
      stimulation of mitral/tufted and centrifugal fiber inputs to granule cells.
AB  - Main olfactory bulb (MOB) granule cells receive spatially segregated
      glutamatergic synaptic inputs from the dendrites of mitral/tufted cells as well
      as from the axons of centrifugal fibers (CFFs) originating in olfactory cortical
      areas. Dendrodendritic synapses from mitral/tufted cells occur on granule cell
      distal dendrites in the external plexiform layer (EPL), whereas CFFs
      preferentially target the somata/proximal dendrites of granule cells in the
      granule cell layer (GCL). In the present study, tract tracing, and recordings of
      field potentials and voltage-sensitive dye optical signals were used to map
      activity patterns elicited by activation of these two inputs to granule cells in
      mouse olfactory bulb slices. Stimulation of the lateral olfactory tract (LOT)
      produced a negative field potential in the EPL and a positivity in the GCL. CFF
      stimulation produced field potentials of opposite polarity in the EPL and GCL to
      those elicited by LOT. LOT-evoked optical signals appeared in the EPL and spread
      subsequently to deeper layers, whereas CFF-evoked responses appeared in the GCL
      and then spread superficially. Evoked responses were reduced by N-methyl-d
      aspartate (NMDA) receptor antagonists and completely suppressed by AMPA receptor
      antagonists. Reduction of extracellular Mg(2+) enhanced the strength and
      spatiotemporal extent of the evoked responses. These and additional findings
      indicate that LOT- and CFF-evoked field potentials and optical signals reflect
      postsynaptic activity in granule cells, with moderate NMDA and dominant AMPA
      receptor components. Taken together, these results demonstrate that LOT and CFF
      stimulation in MOB slices selectively activate glutamatergic inputs to the distal
      dendrites versus somata/proximal dendrites of granule cells.

PMID- 17035368
TI  - Uncovering host defences in the urinary tract: cathelicidin and beyond.

PMID- 17035369
TI  - The potential of matrix metalloproteinase-2 as a marker of peritoneal injury,
      increased solute transport, or progression to encapsulating peritoneal sclerosis
      during peritoneal dialysis--a multicentre study in Japan.
AB  - BACKGROUND: Long-term peritoneal dialysis (PD) leads to peritoneal injury. At
      worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which
      is a serious complication of PD. The mortality rate of EPS is extremely high. To
      perform PD safely, monitoring of peritoneal injury that leads to EPS is a
      necessity. METHODS: A total of 444 PD patients with end-stage renal disease at 60
      centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD
      duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the
      peritoneal effluents were analysed with gelatin zymography or enzyme-linked
      immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were
      investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute
      transport was assessed with the peritoneal equilibration test (PET). RESULTS: The
      MMP-2 levels in peritoneal effluents obtained with the PET were significantly
      correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio
      (R = -0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury,
      moderate peritoneal injury, severe peritoneal injury (EPS) and infectious
      peritonitis were significantly higher than those in control patients (P < 0.001,
      P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by
      myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The
      peritoneal effluents from patients with infectious peritonitis showed strong MMP
      9 signals. CONCLUSIONS: From these results, MMP-2 levels in peritoneal effluents
      reflect peritoneal solute transport and changes in MMP-2 levels are associated
      with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of
      peritoneal injury, increased solute transport or progression to EPS.

PMID- 17035370
TI  - Inequality of renal replacement therapy in the low-income countries.

PMID- 17035371
TI  - Serum phosphate and outcomes in PD patients.

PMID- 17035373
TI  - Ultrapure dialysis fluid--how pure is it and do we need it?

PMID- 17035374
TI  - Drugs as a hidden source of aluminium for chronic renal patients.

PMID- 17035375
TI  - Adherence to peritoneal dialysis training schedule.
AB  - BACKGROUND: Shortening behaviour during peritoneal dialysis training can be
      easily measured, and likened to the skipping behaviour in haemodialysis subjects,
      although its effect on peritoneal dialysis outcomes is now well understood. We
      studied the clinical impact of failing to adhere to a peritoneal dialysis
      training programme among incident dialysis patients. METHODS: This study included
      159 consecutive inception peritoneal dialysis patients in a single centre from
      September 1999 through November 2002. We evaluated the effects of behavioural
      compliance quantified by the per cent time arriving late for scheduled peritoneal
      dialysis training. The patients were categorized by whether they arrived late in
      >20% of their peritoneal dialysis training sessions. RESULTS: Of the 159 incident
      peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal
      dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They
      were younger by 5 years than patients who arrived late < or =20%. Mean
      peritonitis-free time for subjects who arrived late for training in >20% the of
      sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20%
      late attendance behaviour (log rank test, P = 0.038). Multivariable Cox
      proportional hazards analysis showed that late attendance behaviour and baseline
      serum albumin were the only independent risk factors for the time to a first
      peritonitis after adjustment for diabetes mellitus and relevant coexisting
      medical factors. Late arrival in >20% of the peritoneal dialysis training
      sessions was associated with >50% increased likelihood of subsequent peritonitis,
      with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P =
      0.04). CONCLUSION: These findings show that the behavioural measure of late
      attendance for peritoneal dialysis training has a crucial role in predicting
      peritonitis. It may therefore represent a practical strategy for identifying poor
      adherence or predicting medical outcomes.

PMID- 17035376
TI  - How to tackle the avalanche of chronic kidney disease in sub-Saharan Africa: the
      situation in the Democratic Republic of Congo as an example.

PMID- 17035377
TI  - Decreased renal transplant function after parathyroidectomy.
AB  - BACKGROUND: Persistent secondary hyperparathyroidism after renal transplantation
      may require parathyroidectomy (PTX). Clinical experience suggests that these
      patients commonly develop decreased renal function thereafter. METHODS: To test
      this notion, we evaluated 76 transplant patients who underwent pararhyroidectomy
      between 1997 and 2003. RESULTS: In half the patients (47%), creatinine clearance
      decreased >20% (before vs after PTX, 57 +/- 21 vs 38 +/- 17 ml/min, P = 0.001).
      The patients with decreased creatinine clearance had higher parathyroid hormone
      (PTH) concentrations before and lower values after PTX compared with those who
      did not (594 +/- 392 vs 447 +/- 234 pg/ml before PTX, P = 0.03; 35 vs 123 pg/ml
      thereafter, P = 0.002). They also had lower serum calcium concentrations after
      PTX (2.0 vs 2.2 mmol/l, P = 0.005) and they required more calcium and vitamin D
      analogues. These patients also more commonly underwent total PTX with
      autotransplantation, compared with subtotal (75 vs 50%, P = 0.03). However, in
      multivariate analysis, only the delta PTH decline (%) after PTX was a significant
      predictor of deteriorating renal function (P = 0.005) and was correlated with the
      creatinine clearance decrease (R = 0.369, P = 0.001). Prospectively measured
      inulin and para-amino-hippuric acid (PAH) clearance decreased significantly after
      PTX in a subgroup of 19 patients (inulin before vs after PTX 67 vs 55 ml/min/1.73
      m(2), P = 0.001; PAH 360 vs 289 ml/min/1.73 m(2), P = 0.001). Transplant biopsies
      revealed calcification in 70% of biopsied cases. CONCLUSION: Since PTH has a
      known positive regulatory effect on renal perfusion and glomerular filtration
      rate, we conclude that relative hypoparathyroidism after PTX is the main
      mechanism contributing to decreased renal function in these patients. There was
      no difference in 10-year-graft survival between the deteriorating and the non
      deteriorating group.

PMID- 17035378
TI  - Nephrotic syndrome with spontaneous anticoagulant activity.

PMID- 17035379
TI  - The long and winding road of diet and breast cancer prevention.

PMID- 17035380
TI  - Genetic susceptibility to aggressive prostate cancer.

PMID- 17035381
TI  - The enigmatic epidemiology of nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) has a unique and complex etiology that is not
      completely understood. Although NPC is rare in most populations, it is a leading
      form of cancer in a few well-defined populations, including natives of southern
      China, Southeast Asia, the Arctic, and the Middle East/North Africa. The
      distinctive racial/ethnic and geographic distribution of NPC worldwide suggests
      that both environmental factors and genetic traits contribute to its development.
      This review aims to summarize the current knowledge regarding the epidemiology of
      NPC and to propose new avenues of research that could help illuminate the causes
      and ultimately the prevention of this remarkable disease. Well-established risk
      factors for NPC include elevated antibody titers against the Epstein-Barr virus,
      consumption of salt-preserved fish, a family history of NPC, and certain human
      leukocyte antigen class I genotypes. Consumption of other preserved foods,
      tobacco smoking, and a history of chronic respiratory tract conditions may be
      associated with elevated NPC risk, whereas consumption of fresh fruits and
      vegetables and other human leukocyte antigen genotypes may be associated with
      decreased risk. Evidence for a causal role of various inhalants, herbal
      medicines, and occupational exposures is inconsistent. Other than dietary
      modification, no concrete preventive measures for NPC exist. Given the unresolved
      gaps in understanding of NPC, there is a clear need for large-scale, population
      based molecular epidemiologic studies to elucidate how environmental, viral, and
      genetic factors interact in both the development and the prevention of this
      disease.

PMID- 17035382
TI  - The case for a genetic predisposition to serrated neoplasia in the colorectum:
      hypothesis and review of the literature.
AB  - In recent years, an alternative pathway of colorectal cancer development has been
      described in which serrated polyps replace the traditional adenoma as the
      precursor lesion. Importantly, serrated polyps and a subset of colorectal cancer
      show largely nonoverlapping mutation profiles to those found in adenomas and the
      majority of colorectal cancer. These genetic alterations include activating
      mutation of the BRAF proto-oncogene and widespread gene promoter hypermethylation
      (CpG island methylator phenotype or CIMP). Up to 15% of colorectal cancer is
      likely to develop on the basis of a strong genetic predisposition. The two most
      well-characterized syndromes, familial adenomatous polyposis and hereditary
      nonpolyposis colorectal cancer (Lynch syndrome), both develop via the adenoma
      carcinoma pathway and together account for approximately one third of familial
      colorectal cancer. We have recently described 11 families in which there is
      evidence that the genetic predisposition to autosomal dominant colorectal cancer
      is linked to the serrated pathway. This condition, serrated pathway syndrome, and
      the related condition, hyperplastic polyposis, the presentation of which suggests
      a recessive mode of inheritance, represent two syndromes in which BRAF mutation
      and methylation co-occur within serrated precursor lesions. Further, CIMP is
      observed in the normal colonic mucosa of individuals with hyperplastic polyposis
      consistent with a field defect in epigenetic regulation. The spectrum of serrated
      neoplasia may also implicate the apparently sporadic and later onset subset of
      colorectal cancer with high levels of microsatellite instability. The tendency
      for these lesions to be multiple, associated with smoking, and to show frequent
      BRAF mutation and CIMP points to a defect that may result from interactions
      between the environment and a weakly penetrant genetic alteration.

PMID- 17035383
TI  - Nonsteroidal anti-inflammatory drugs and subsite-specific colorectal cancer
      incidence in the Iowa women's health study.
AB  - BACKGROUND: Previous epidemiologic studies have shown that regular use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with decreased
      colorectal cancer risk. However, few studies have examined associations between
      NSAID use and subsite-specific colorectal cancer risks. Because tumors of the
      proximal and distal colon differ with respect to their genetic alterations,
      clinicopathologic features, and demographic distribution, further investigation
      of subsite-specific colorectal cancer risks may be rewarding. METHODS: Data about
      aspirin and non-aspirin-NSAID use were recorded by self-report in 1992 among the
      initially cancer-free cohort of postmenopausal women in the Iowa Women's Health
      Study (n = 27,160). In total, 637 women developed colorectal cancer during the 11
      years of follow-up, including 365 proximal colon, 132 distal colon, and 120
      rectal cancer cases (11 overlapping and 9 not specified). RESULTS: For colon
      cancer, the multivariable-adjusted hazard ratios (HR) for women reporting use of
      aspirin two to five times and six or more times weekly (compared with nonusers of
      aspirin) were 0.79 [95% confidence interval (95% CI), 0.59-1.04] and 0.76 (95%
      CI, 0.58-1.00), respectively. The corresponding HRs for non-aspirin NSAIDs were
      0.63 (95% CI, 0.41-0.96) and 0.85 (95% CI, 0.63-1.15), respectively. For proximal
      colon cancer, the multivariable-adjusted HRs for women reporting use of aspirin
      or non-aspirin NSAIDs two or more times weekly (compared with nonusers of each)
      were 0.67 (95% CI, 0.51-0.87) and 0.71 (95% CI, 0.52-0.97), respectively. No
      statistically significant association was found between either distal colon or
      rectal cancer and aspirin or non-aspirin NSAID use. DISCUSSION: Our study is
      consistent with a limited number of prior reports that have observed stronger
      associations between NSAID use and proximal versus distal colorectal cancer.

PMID- 17035384
TI  - Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as
      biomarkers for dietary intakes of fish, fat, and fatty acids.
AB  - Consumption of fish rich in n-3 polyunsaturated fatty acids (PUFAs), such as
      docosahexaenoic acid, is suggested to reduce colorectal cancer risk through
      inhibition of the arachidonic acid (AA) cascade related to tumorigenesis and cell
      proliferation. High intake of saturated fatty acids (SFAs) may increase the risk.
      To examine associations between colorectal cancer risk and fatty acid
      compositions in erythrocyte membranes, as biomarkers for dietary intakes of fish,
      fat, and fatty acids, we conducted a case-control study with 74 incident cases
      and 221 noncancer controls (matched by age, sex, and season of sample
      collection). Erythrocyte fatty acids were measured using an accelerated solvent
      extraction and a gas-liquid chromatography. Colorectal cancer had no association
      with dietary intakes of meat, fish, fat, and fatty acids. However, the risk was
      inversely associated with erythrocyte compositions of docosahexaenoic acid, AA,
      and PUFAs [the highest to the lowest tertile, odds ratios, 0.36, 0.42, and 0.15;
      95% confidence intervals, 0.14-0.93, 0.18-0.95, and 0.05-0.46; P(trend) < 0.05,
      respectively] and positively with those of palmitic acid, SFAs, and the ratio of
      SFAs/PUFAs (odds ratios, 6.46, 8.20, and 9.45; 95% confidence intervals, 2.41
      17.26, 2.86-23.52, and 2.84-31.43; P(trend) < 0.005, respectively). In
      conclusion, we could clearly show decreased and increased risks for colorectal
      cancer related to PUFAs and SFAs compositions in erythrocyte membranes,
      respectively, but further research is needed to investigate the discrepancy
      between our findings and the generally accepted role of the AA cascade.

PMID- 17035385
TI  - Comparison of polymorphisms in genes involved in polycyclic aromatic hydrocarbon
      metabolism with urinary phenanthrene metabolite ratios in smokers.
AB  - The hypothesis that interindividual differences among smokers in the metabolism
      of polycyclic aromatic hydrocarbons (PAH) are related to lung cancer risk has
      been extensively investigated in the literature. These studies have compared lung
      cancer risk in groups of smokers with or without polymorphisms in genes involved
      in PAH metabolism. We believe that carcinogen metabolite phenotyping, involving
      the actual measurement of PAH metabolites, would be a better way to investigate
      differences in lung cancer risk. With this goal in mind, we have developed
      methods for quantifying phenanthrene metabolites in urine. Phenanthrene is the
      simplest PAH with a bay region, a feature closely associated with
      carcinogenicity. The urinary metabolite r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4
      tetrahydrophenanthrene (PheT) is a measure of metabolic activation, whereas
      phenanthrols (HOPhe) are a measure of detoxification. In this study, we
      quantified urinary PheT/HOPhe ratios in 346 smokers who were also genotyped for
      11 polymorphisms in genes involved in PAH metabolism: CYP1A1MspI, CYP1A1I462V,
      CYP1B1R48G, CYP1B1A119S, CYP1B1L432V, CYP1B1N453S, EPHX1Y113H, EPHX1H139R,
      GSTP1I105V, GSTP1A114V, and GSTM1 null. The geometric mean molar PheT/3-HOPhe
      ratio was 4.08 (95% confidence interval, 3.79-4.39). Ten percent of the smokers
      had PheT/3-HOPhe ratios of > or =9.90. We found a significant association between
      the presence of the CYP1A1I462V polymorphism and high PheT/3-HOPhe ratios (P =
      0.02). This effect was particularly strong in females and in combination with the
      GSTM1 null polymorphism. In contrast, the CYP1B1R48G and CYP1B1A119S
      polymorphisms were associated with significantly lower PheT/3-HOPhe ratios,
      particularly in Blacks. There were no consistent significant effects of any of
      the other polymorphisms on PheT/3-HOPhe ratios. The highest 10% of PheT/3-HOPhe
      ratios could not be predicted by the presence of any of the 11 polymorphisms
      individually or by certain combinations. The effects of the CYP1A1I462
      polymorphism observed here, particularly in combination with GSTM1 null, are
      quite consistent with reports in the literature. However, the results of this
      study indicate that genotyping is not an effective way to predict PAH metabolism
      at least as represented by PheT/HOPhe ratios.

PMID- 17035386
TI  - CYP2A6 genotype, phenotype, and the use of nicotine metabolites as biomarkers
      during ad libitum smoking.
AB  - CYP2A6 inactivates nicotine to cotinine and cotinine to 3-hydroxycotinine. We
      investigated which of plasma nicotine and metabolites were most related to CYP2A6
      genotype and smoking levels. We assessed demographic and smoking histories in 152
      Caucasian ad libitum smokers, measured breath carbon monoxide (CO) levels, and
      determined plasma nicotine, cotinine, and 3-hydroxycotinine by high-performance
      liquid chromatography and CYP2A6 genotypes by PCR. Cigarettes per day was most
      closely related to CO (r = 0.60, P < 0.001) followed by plasma cotinine (r =
      0.53, P < 0.001), whereas plasma cotinine was most strongly correlated with CO
      levels (r = 0.74, P < 0.001), confirming that cotinine is a good indicator of
      smoking levels; this was not limited by CYP2A6 variants. 3
      Hydroxycotinine/cotinine is reported to be a good marker of CYP2A6 activity, and
      we found that the 3-hydroxycotinine/(cotinine + nicotine) ratio was most
      correlated with CYP2A6 genotype (r = 0.38, P < 0.001). Inclusion of the
      CYP2A6*12A allele strengthened the correlation (r = 0.46, P < 0.001), suggesting
      that the identification of novel alleles will continue to improve this
      relationship. Nicotine metabolism is slower in smokers, and we have shown that
      CYP2A6 is reduced by nicotine treatment in monkeys. Here, we found that plasma
      nicotine levels were inversely correlated with CYP2A6 activity (3
      hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6
      variants, suggesting a reduction in metabolism with higher nicotine levels.
      Together, these findings (a) confirm the use of plasma cotinine and CO as
      indicators of Caucasians' smoking levels, and that this is not limited by CYP2A6
      genetic variation; (b) indicate that 3-hydroxycotinine/cotinine and 3
      hydroxycotinine/(cotinine + nicotine) are moderately good indicators of the
      CYP2A6 genotype; and (c) support that nicotine exposure may reduce its own
      metabolism.

PMID- 17035387
TI  - Maternal smoking and testicular germ cell tumors.
AB  - Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15
      to 35 years in the United States. The well-established TGCT risk factors
      cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer
      indicate that exposures in early life and/or in the familial setting may be
      critical to determining risk. Previous reports of familial clustering of lung
      cancer in mothers and testicular cancers in sons suggest that passive smoking in
      childhood may be such an exposure. To clarify the relationship of passive smoking
      exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the
      Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were
      analyzed. Data from 1,086 mothers of the cases and controls were also examined.
      Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95%
      confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8
      1.3) and TGCT risk. Although living with a non-parent smoker was marginally
      related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number
      of smokers, amount smoked, or duration of smoking. Responses from both case
      control participants and mothers also revealed no relationship between either
      maternal smoking while pregnant or while breast-feeding. Results did not differ
      by TGCT histology (seminoma, non-seminoma). These results do not support the
      hypothesis that passive smoking, either in utero or in childhood, is related to
      risk of TGCT. Other early life exposures, however, may explain the familial
      clustering of lung cancer in mothers and TGCT in sons.

PMID- 17035388
TI  - Validity of self-reported smoking status among participants in a lung cancer
      screening trial.
AB  - Lung cancer remains a devastating disease associated with substantial morbidity
      and mortality. Recent research has suggested that lung cancer screening with
      spiral computed tomography scans might reduce lung cancer mortality. Studies of
      lung cancer screening have also suggested that significant numbers of
      participants quit smoking after screening. However, most have relied solely on
      self-reported smoking behavior, which may be less accurate among participants in
      lung cancer screening. To assess the validity of self-reported smoking status
      among participants in a lung cancer screening trial, this study compared self
      reported smoking status against urinary cotinine levels. The sample included 55
      consecutive participants enrolled in a randomized clinical trial comparing annual
      spiral computed tomography and chest X-ray for lung cancer screening.
      Participants were a mean of 59 years of age and predominantly Caucasian (96%) and
      male (55%). Self-reported smoking status was assessed before and after
      participants learned of the purpose of the biochemical verification study. Using
      urinary cotinine as the "gold standard," the sensitivity and specificity of self
      reported smoking status were 91% and 95%, respectively (kappa = 0.85, P < 0.001,
      95% confidence interval = 0.71-0.99). Total misclassification rate was 7%.
      However, three of the four misclassified participants reported concurrent use of
      nicotine replacement strategies. Eliminating these cases from the analysis
      revealed sensitivity of 100% and specificity of 95% (kappa = 0.96, P < 0.001, 95%
      confidence interval = 0.88-1.00). In conclusion, self-reported smoking status
      among participants in a lung cancer screening trial was highly consistent with
      urinary cotinine test results.

PMID- 17035389
TI  - Marijuana use and the risk of lung and upper aerodigestive tract cancers: results
      of a population-based case-control study.
AB  - BACKGROUND: Despite several lines of evidence suggesting the biological
      plausibility of marijuana being carcinogenic, epidemiologic findings are
      inconsistent. We conducted a population-based case-control study of the
      association between marijuana use and the risk of lung and upper aerodigestive
      tract cancers in Los Angeles. METHODS: Our study included 1,212 incident cancer
      cases and 1,040 cancer-free controls matched to cases on age, gender, and
      neighborhood. Subjects were interviewed with a standardized questionnaire. The
      cumulative use of marijuana was expressed in joint-years, where 1 joint-year is
      equivalent to smoking one joint per day for 1 year. RESULTS: Although using
      marijuana for > or =30 joint-years was positively associated in the crude
      analyses with each cancer type (except pharyngeal cancer), no positive
      associations were observed when adjusting for several confounders including
      cigarette smoking. The adjusted odds ratio estimate (and 95% confidence limits)
      for > or =60 versus 0 joint-years was 1.1 (0.56, 2.1) for oral cancer, 0.84
      (0.28, 2.5) for laryngeal cancer, and 0.62 (0.32, 1.2) for lung cancer; the
      adjusted odds ratio estimate for > or =30 versus 0 joint-years was 0.57 (0.20,
      1.6) for pharyngeal cancer, and 0.53 (0.22, 1.3) for esophageal cancer. No
      association was consistently monotonic across exposure categories, and
      restriction to subjects who never smoked cigarettes yielded similar findings.
      CONCLUSIONS: Our results may have been affected by selection bias or error in
      measuring lifetime exposure and confounder histories; but they suggest that the
      association of these cancers with marijuana, even long-term or heavy use, is not
      strong and may be below practically detectable limits.

PMID- 17035390
TI  - Effect of staining procedures on the results of micronucleus assays with
      exfoliated oral mucosa cells.
AB  - Micronuclei in exfoliated epithelial cells are widely used as biomarkers of
      cancer risk in humans. To elucidate the effect of different staining procedures
      on the outcome of such investigation, we conducted a study in which the
      micronuclei frequencies in oral mucosa cells of heavy smokers (n = 20) and
      nonsmokers (n = 10) were evaluated with nonspecific (Giemsa, May-Grunwald-Giemsa)
      and DNA-specific (4',6-diamidino-2-phenylindole, Feulgen, acridine orange)
      stains, whereas with Giemsa-based stains, the frequencies of micronuclei in
      smokers were significantly (4- to 5-fold) higher in the smokers group, no
      significant increase was observed with any of the DNA-specific stains.
      Furthermore, the evaluation of cells of the two study groups with Feulgen stain
      showed that oral mucosa cells from smokers had significantly increased levels of
      nuclear anomalies other than micronuclei. These anomalies are consequences of
      cell injury found in epithelial cells and are paralleled by formation of keratin
      bodies in the cytoplasm that resemble micronuclei. Correlation analyses showed
      that micronuclei frequencies scored in Giemsa-stained slides correlated
      significantly with karyorrhexis, karyolysis, condensed chromatin, and
      binucleates, whereas no such correlations were found with DNA-specific stains.
      These findings indicate that nuclear anomalies (and possibly keratin bodies) may
      be misinterpreted as micronuclei with nonspecific DNA stains and lead to false
      positive results in studies with cells of epithelial origin. Furthermore, our
      results show that exposure of oral mucosa cells to genotoxic carcinogens
      contained in tobacco smoke does not lead to induction of micronuclei in these
      cells.

PMID- 17035392
TI  - Influence of patterns of hormone replacement therapy use and mammographic density
      on breast cancer detection.
AB  - BACKGROUND: There is evidence that factors such as current hormone replacement
      therapy (HRT) use and mammographic density may each lower the sensitivity of
      mammography and are associated with a greater risk of developing an interval
      cancer. This study explores this relationship further by examining the influence
      of patterns of HRT use and the percentage of mammographic density on the
      detection of breast cancer by classification of interval cancer. METHODS: This
      study uses a case-case design nested within a cohort of women screened by the
      Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both
      those missed at screening but seen on retrospective review (n = 87) or true
      intervals without visible tumor signs at screening (n = 288) were matched to 450
      screen-detected cancers. The association between the percentage of mammographic
      density, measured by radiologists and a computer-assisted method, and HRT use,
      ascertained from a mailed questionnaire, and the risk of being diagnosed with an
      interval cancer was estimated using conditional logistic regression. RESULTS: A
      monotonic gradient of increasing risk for interval cancers was found for each 25%
      increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals
      (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true
      intervals]. After adjusting for mammographic density, a significantly increased
      risk for true-interval cancers remained for women taking estrogen alone (OR,
      1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and
      true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined
      HRT. CONCLUSIONS: Information on mammographic density and HRT use should
      routinely be collected at the time of screening. Women at risk should be made
      aware of the lower sensitivity of mammography and offered alternative procedures
      for screening.

PMID- 17035391
TI  - Racial/ethnic differences in postmenopausal endogenous hormones: the multiethnic
      cohort study.
AB  - Postmenopausal women with increased estrogens and lowered sex hormone-binding
      globulin (SHBG) concentrations are at increased risk of breast cancer. In the
      Multiethnic Cohort Study, the highest incidence rates of postmenopausal breast
      cancer were observed among Native Hawaiians followed by Japanese Americans,
      Whites, African Americans, and Latinas. Ethnic differences in endogenous sex
      hormone profiles may contribute to some of the variation in breast cancer
      incidence. Plasma concentrations of androstenedione, testosterone, estrone
      (E(1)), estradiol (E(2)), and SHBG were measured in 739 postmenopausal women from
      the Multiethnic Cohort Study (240 African Americans, 81 Native Hawaiians, 96
      Japanese Americans, 231 Latinas, and 91 Whites). After adjusting for age, known
      breast cancer risk factors and lifestyle factors, the mean levels of
      testosterone, estrogen, and SHBG varied across populations (Ps < or = 0.004).
      Across racial/ethnic groups, Native Hawaiians had the highest mean levels of
      androstenedione, testosterone, and estrogens and the lowest mean levels of SHBG.
      Compared with Whites, Native Hawaiians had higher androstenedione (+22%, P =
      0.017), total testosterone (+26%, P = 0.013), bioavailable testosterone (+33%, P
      = 0.002), E(1) (> or =21%; P = 0.009), total E(2) (+26%, P = 0.001), bioavailable
      E(2) (+31%, P < 0.001), and lower SHBG (-12% P = 0.07) levels. Compared with
      Whites, Japanese Americans had higher E(2) (+15%, P = 0.036) and bioavailable
      E(2) (+18%, P = 0.024) levels. African Americans also had higher E(1) (+21%, P =
      0.004), E(2) (+20%, P = 0.007), and bioavailable E(2) (+20%, P = 0.015) levels
      compared with Whites, whereas mean levels in Latinas were similar to those of
      Whites. Many of the differences in endogenous postmenopausal hormonal milieu
      across these five racial/ethnic groups are consistent with the known differences
      in breast cancer incidence across these populations.

PMID- 17035393
TI  - General and abdominal obesity and survival among young women with breast cancer.
AB  - Among postmenopausal women, obesity is linked to increased risk of breast cancer
      and poorer subsequent survival. For premenopausal women, obesity may reduce
      incidence, but less is known about its effect on prognosis, particularly for
      abdominal obesity. This study investigated whether general or abdominal obesity
      at diagnosis influenced survival in a cohort of young women with breast cancer. A
      population-based follow-up study was conducted among 1,254 women ages 20 to 54
      who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta
      or New Jersey. Women were interviewed within several months of diagnosis and
      asked about their weight and height at age 20 and in the year before diagnosis.
      Study personnel did anthropometric measures at the interview. With 8 to 10 years
      of follow-up, all-cause mortality status was determined using the National Death
      Index (n = 290 deaths). Increased mortality was observed for women who were obese
      [body mass index (BMI), > or =30] at the time of interview compared with women of
      ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48;
      95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the
      highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05
      2.19). Strong associations with mortality were found for women who were obese at
      age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, > or =25)
      at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This
      study provides evidence that breast cancer survival is reduced among younger
      women with general or abdominal obesity.

PMID- 17035394
TI  - Genetic ancestry and risk factors for breast cancer among Latinas in the San
      Francisco Bay Area.
AB  - BACKGROUND: Genetic association studies using case-control designs are
      susceptible to false-positive and false-negative results if there are differences
      in genetic ancestry between cases and controls. We measured genetic ancestry
      among Latinas in a population-based case-control study of breast cancer and
      tested the association between ancestry and known breast cancer risk factors. We
      reasoned that if genetic ancestry is associated with known breast cancer risk
      factors, then the results of genetic association studies would be confounded.
      METHODS: We used 44 ancestry informative markers to estimate individuals' genetic
      ancestry in 563 Latina participants. To test whether ancestry is a predictor of
      hormone therapy use, parity, and body mass index (BMI), we used multivariate
      logistic regression models to estimate odds ratios (OR) and 95% confidence
      intervals (95% CI) associated with a 25% increase in Indigenous American
      ancestry, adjusting for age, education, and the participant's and grandparents'
      place of birth. RESULTS: Hormone therapy use was significantly less common among
      women with higher Indigenous American ancestry (OR, 0.78; 95% CI, 0.63-0.96).
      Higher Indigenous American ancestry was also significantly associated with
      overweight (BMI, 25-29.9 versus <25) and obesity (BMI, > or =30 versus <25), but
      only among foreign-born Latina women (OR, 3.44; 95% CI, 1.97-5.99 and OR, 1.95;
      95% CI, 1.24-3.06, respectively). CONCLUSION: Some breast cancer risk factors are
      associated with genetic ancestry among Latinas in the San Francisco Bay Area.
      Therefore, case-control genetic association studies for breast cancer should
      directly measure genetic ancestry to avoid potential confounding.

PMID- 17035395
TI  - Increases in plasma carotenoid concentrations in response to a major dietary
      change in the women's healthy eating and living study.
AB  - BACKGROUND: Cohort studies suggest that higher circulating carotenoid
      concentrations through food sources may reduce breast cancer events. Other
      intervention studies have not achieved the level of change in circulating
      carotenoids required to properly test this hypothesis. METHODS: In a randomized
      trial of 2,922 breast cancer survivors, we examined blood and self-reported diet
      at baseline and 1 year. Intensive telephone counseling encouraged a plant-based
      diet in the intervention group. Diet was measured via 24-hour recalls, and a
      panel of plasma carotenoid concentrations was assessed at both time points.
      RESULTS: The study intervention was associated with a 51% increase in total
      carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L,
      achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta
      carotene, and lutein. For each of these targeted carotenoids, the proportion of
      the intervention sample remaining below the cutpoint for the lowest baseline
      quartile decreased by one third to one half. After 1 year of study, half of the
      intervention group was in the highest baseline quartile. No change in
      distribution was observed in comparison group. Intervention participants achieved
      this change by both dietary pattern and vegetable juice consumption. Participants
      who chose to change dietary pattern without consuming significant quantities of
      vegetable juice achieved 75% of the level of change observed in other
      intervention participants. CONCLUSIONS: Innovative telephone counseling
      intervention and dietary targets in the Women's Healthy Eating and Living study
      were associated with the level of change in circulating carotenoid concentration
      necessary to test the diet and breast cancer hypothesis suggested by cohort
      studies.

PMID- 17035396
TI  - Measuring perceptions of breast cancer risk.
AB  - BACKGROUND: Accurate measurement of people's risk perceptions is important for
      numerous bodies of research and in clinical practice, but there is no consensus
      about the best measure. OBJECTIVE: This study evaluated three measures of women's
      breast cancer risk perception by assessing their psychometric and test
      characteristics. DESIGN: A cross-sectional mailed survey to women from a primary
      care population asked participants to rate their chance of developing breast
      cancer in their lifetime on a 0% to 100% numerical scale and a verbal scale with
      five descriptive categories, and to compare their risk to others (seven
      categories). Six hundred three of 956 women returned the survey (63.1%), and we
      analyzed surveys from the 566 women without a self-reported personal history of
      breast or ovarian cancer. RESULTS: Scores on the numeric, verbal, and comparative
      measures were correlated with each other (r > 0.50), worry (r > 0.51), the Gail
      estimate (r > 0.26), and family history (r > 0.25). The numerical scale had the
      strongest correlation with annual mammogram (r = 0.19), and its correlation with
      the Gail estimate was unassociated with participants' sociodemographics. The
      numerical and comparative measures had the highest sensitivity (0.89-0.90) and
      specificity (0.99) for identifying women with very high risk perception. The
      numerical and comparative scale also did well in identifying women with very low
      risk perception, although the numerical scale had the highest specificity (0.96),
      whereas the comparative scale had the highest sensitivity (0.89). CONCLUSION:
      Different measures of women's perceptions about breast cancer risk have different
      strengths and weaknesses. Although the numerical measure did best overall, the
      optimal measure depends on the goals of the measure (i.e., avoidance of false
      positives or false negatives).

PMID- 17035397
TI  - Comparison of age distribution patterns for different histopathologic types of
      breast carcinoma.
AB  - BACKGROUND: Historically, female breast carcinoma has been viewed as an
      etiologically homogeneous disease associated with rapidly increasing incidence
      rates until age 50 years, followed by a slower rate of increase among older
      women. More recent studies, however, have shown distinct age incidence patterns
      for female breast cancer when stratified by estrogen receptor (ER) expression
      and/or histopathologic subtypes, suggesting etiologic heterogeneity. MATERIALS
      AND METHODS: To determine if different age incidence patterns reflect etiologic
      heterogeneity (more than one breast cancer type within the general breast
      carcinoma), we applied "smoothed" age histograms at diagnosis (density plots) and
      a two-component statistical mixture model to all breast carcinoma cases (n =
      270,124) in the Surveillance, Epidemiology, and End Results Program of the
      National Cancer Institute. These overall patterns were then reevaluated according
      to histopathologic type, race, and ER expression. RESULTS: A bimodal age
      distribution at diagnosis provided a better fit to the data than a single density
      for all breast carcinoma populations, except for medullary carcinoma. Medullary
      carcinomas showed a single age distribution at diagnosis irrespective of race
      and/or ER expression. CONCLUSIONS: Distinct age-specific incidence patterns
      reflected bimodal breast cancer populations for breast carcinoma overall as well
      as for histopathologic subtypes, race, and ER expression. The one exception was
      medullary carcinoma. Of note, medullary carcinomas are rare tumors, which are
      associated with germ-line mutations in the BRCA1 gene. These descriptive and
      model-based results support emerging molecular data, suggesting two main types of
      breast carcinoma in the overall breast cancer population.

PMID- 17035398
TI  - The P2X7 receptor: a novel biomarker of uterine epithelial cancers.
AB  - OBJECTIVE: To determine expression of the P2X(7) receptor in normal and in cancer
      uterine tissues. The rationale was that the receptor P2X(7) regulates
      constitutive apoptosis in uterine epithelial cells, and previous studies showed
      diminished P2X(7)-mediated apoptosis in cancer uterine cells compared with normal
      cells. METHODS: A clinical, experimental feasibility study. Normal (n = 42) and
      cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to
      75. End points for P2X(7) mRNA were quantitative PCR and in situ hybridization,
      and end points for P2X(7) protein were Western blots and immunostaining using
      anti-P2X(7) antibody. RESULTS: (a) In normal uteri, P2X(7) mRNA and protein were
      expressed predominantly in the epithelial (endometrial, endocervical, and
      ectocervical) cells. (b) Expression of the P2X(7) mRNA and protein was absent
      from endometrial and endocervical adenocarcinoma tissues and from cervical
      squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X(7) protein was
      absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X(7) mRNA
      (normalized in each tissue to the constitutive glyceraldehyde-3-phosphate
      dehydrogenase) and P2X(7) protein levels (normalized in each tissue to the
      constitutive tubulin) revealed that P2X(7) mRNA and/or protein levels can
      distinguish uterine normal from cancer tissues at high degrees of sensitivity
      (92%, 100%) and specificity (100%, 90%). SUMMARY AND CONCLUSIONS: (a) Levels of
      the P2X(7) are lower in uterine epithelial cancer tissues than in the
      corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and
      protein levels could be used as a novel biomarker to differentiate normal and
      cancer uterine epithelial tissues.

PMID- 17035399
TI  - A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian
      cancer.
AB  - PURPOSE: To evaluate study feasibility, toxicity, drug concentrations, and
      activity of escalating doses of the synthetic retinoid fenretinide [N-(4
      hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and
      cytomorphometric biomarkers in cancer cells collected from ascitic fluid before
      and after treatment. METHODS: Twenty-two naive patients with ascitic ovarian
      cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d
      for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells
      expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area,
      DNA index, and chromatin texture) were determined in ascitic cells. Drug levels
      were measured by high-performance liquid chromatography. RESULTS: Doses up to 800
      mg/d were well tolerated, and no adverse reactions occurred. There was no effect
      of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75%
      of subjects, and cytomorphometric variables, which were assessed in 80% of
      subjects. Plasma retinol levels were significantly lower in affected women than
      healthy donors. 4-HPR plasma concentrations increased slightly with increasing
      doses and attained a 1.4 micromol/L concentration with 800 mg/d. Drug levels in
      malignant ascitic cells and tumor tissue were higher than in plasma but were 50
      and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1
      micromol/L 4-HPR. CONCLUSIONS: Cell biomarkers can be measured in ascitic cells
      to assess drug activity. Under our experimental conditions, 4-HPR did not show
      activity in advanced ovarian cancer cells. However, clinical evidence supports
      further investigation of fenretinide for ovarian cancer prevention.

PMID- 17035400
TI  - Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis.
AB  - Some studies have reported that proinflammatory polymorphisms in interleukin-1B
      (IL-1B) and IL-1 receptor antagonist (IL-1RN) genes are associated with increased
      gastric cancer risk. However, other studies have shown null or inverse
      associations. This meta-analysis reviews and summarizes published evidence for
      these associations. Searching the PubMed Database yielded 35 studies that
      reported on the association between IL-1B -511 C>T, IL-1B -31 T>C, or IL-1RN
      variable number tandem repeat polymorphisms and gastric cancer risk. Q-statistics
      and I(2) statistics were calculated to examine heterogeneity. Summary odds ratios
      (OR) and 95% confidence intervals (95% CI) were calculated in the random-effects
      model using the DerSimonian-Laird method. For all gastric cancers, the overall
      ORs (95% CIs) for IL-1B -511 CT versus CC and TT versus CC genotypes were 1.07
      (0.91-1.25) and 1.16 (0.95-1.42), respectively. ORs (95% CIs) for the association
      between IL-1B -31 CT versus TT and CC versus TT genotypes were 0.99 (0.83-1.19)
      and 0.98 (0.78-1.21), respectively. For the associations between IL-1RN and
      gastric cancer, ORs (95% CIs) for *2/L versus LL and *2/*2 versus L/L were 1.15
      (0.96-1.38) and 1.23 (0.79-1.92). For each of the examined associations, there
      was significant heterogeneity among studies; P(heterogeneity) < or = 0.001 and
      I(2) ranged from 0.54 to 0.71. Noncardia cancers showed stronger associations
      with IL-1B -511 CT or TT and IL1-RN *2/*2 genotypes, but limiting the analysis to
      intestinal-type cancers, studies conducted in Western countries, or studies in
      which polymorphisms were in Hardy-Weinberg equilibrium, made no material
      difference in the results. The overall associations between IL-1B or IL-1RN
      proinflammatory polymorphisms and gastric cancer were null but several studies
      showed an association. The sources of this variation are unclear.

PMID- 17035401
TI  - Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on
      gastric cancer risks in Japan.
AB  - BACKGROUNDS AND AIMS: The renin-angiotensin system plays an important role in
      homeostasis. Angiotensin II, which is generated by chymase and angiotensin I
      converting enzyme (ACE), controls blood pressure as well as angiogenesis and cell
      proliferation. The aim of this study was to clarify the association of the
      chymase gene (CMA/B) and ACE polymorphisms with susceptibility to gastric cancer
      and peptic ulcer. METHODS: We assessed CMA/B A/G and ACE insertion/deletion (I/D)
      polymorphisms in H. pylori-positive gastric cancers (n = 119), gastric ulcers (n
      = 127), and duodenal ulcers (n = 105), and controls (n = 294) consisting of H.
      pylori-positive gastritis alone (n = 162) and H. pylori-negative subjects (n =
      132) by PCR methods. RESULTS: In CMA/B polymorphism, the age- and sex-adjusted
      odds ratios (OR) of A/A and A/G genotypes relative to the G/G genotype for
      gastric cancer risk were 7.115 (95% confidence interval, 1.818-27.845) and 1.956
      (95% confidence interval, 1.137-3.366), respectively. There was an increased risk
      for gastric ulcer in the A/A genotype (OR, 3.450; 1.086-10.960). However, there
      was no association between ACE polymorphism and susceptibility to gastric cancer
      and peptic ulcer. In allele combination analysis of CMA/B and ACE polymorphisms,
      the A/I allele combinations (CMA/B G/A or A/A and ACE I/I genotype) significantly
      increased the risk of gastric cancer development (OR, 4.749, 2.050-11.001)
      compared with the G/I allele combinations (CMA/B G/G and ACE I/I genotype).
      CONCLUSIONS: The CMA/B polymorphism was associated with an increased risk for
      gastric cancer and gastric ulcer development. The genotyping test of the renin
      angiotensin system could be useful for the screening of individuals with higher
      risks of gastric cancer and gastric ulcer.

PMID- 17035403
TI  - Cyclin E expression and outcome in pancreatic ductal adenocarcinoma.
AB  - The association of high cyclin E expression with poor outcome in some cancers, in
      particular breast cancer, suggests that it may play an important role in tumor
      biology. Because the influence of cyclin E expression on outcome is yet to be
      examined in pancreatic cancer, we assessed the relationship between the
      expression of cyclin E, p27(Kip1), and survival in a large cohort of pancreatic
      cancer patients with long-term follow-up. Expression of cyclin E and p27(Kip1)
      was assessed by immunohistochemistry using tissue microarrays of tumor samples
      from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43
      biopsies). High cyclin E expression (>10% positive nuclei) was identified in 39
      of 118 (33%) patients. This was associated with poor prognosis on univariate
      analysis in the whole cohort (P = 0.005), as well as in the subgroup of 75
      patients who underwent operative resection (P = 0.04). On multivariate analysis,
      high cyclin E expression was an independent predictor of poor survival in both
      the entire cohort (P = 0.005) and the resected subgroup (P = 0.03), and was
      superior to all tested clinicopathologic factors (tumor size, lymph node
      metastases, differentiation, margin involvement, and perineural invasion) as a
      marker of survival. Low p27(Kip1) expression (<5% positive nuclei) was present in
      41 of 111 (37%) patients, but was not associated with survival, and coexpression
      of p27(Kip1) did not influence the association of high cyclin E expression with
      poor survival. High cyclin E expression is a strong independent predictor of poor
      outcome in patients with pancreatic cancer. Thus, if these data are confirmed in
      independent cohorts, measurement of cyclin E may add significant prognostic
      information to the currently used clinicopathologic variables and hence have
      potential clinical utility in the management of this disease.

PMID- 17035402
TI  - Mutagen sensitivity and neoplastic progression in patients with Barrett's
      esophagus: a prospective analysis.
AB  - BACKGROUND: Defects in DNA damage recognition and repair have been associated
      with a wide variety of cancers. We conducted a prospective study to determine
      whether mutagen sensitivity, as determined by an in vitro assay, was associated
      with the future development of cancer in patients with Barrett's esophagus, which
      is associated with increased risk of progression to esophageal adenocarcinoma.
      METHODS: We measured sensitivity to bleomycin in peripheral blood lymphocytes in
      a cohort of 220 patients with Barrett's esophagus. We followed these patients for
      1,230 person-years (range, 3 months to 10.1 years; median, 6.4 years), using
      development of cancer and aneuploidy as end points. A subset of these patients
      was evaluated for inactivation of tumor-suppressor genes CDKN2A/p16 and TP53 [by
      mutation and loss of heterozygosity (LOH)] in their Barrett's segments at the
      time of, or before, the bleomycin test, and the patients were stratified by
      CDKN2A/p16 and TP53 status in an analysis of mutagen sensitivity and progression.
      RESULTS: Bleomycin-sensitive patients were found to be at significantly greater
      risk of developing aneuploidy (adjusted hazard ratio, 3.71; 95% confidence
      interval, 1.44-9.53) and nonsignificantly greater risk of cancer (adjusted hazard
      ratio, 1.63; 95% confidence interval, 0.71-3.75). Among patients with detectable
      LOH at the TP53 locus (on chromosome 17p), increasing bleomycin sensitivity was
      associated with increased risk of developing cancer (P(trend) < 0.001) and
      aneuploidy (P(trend) = 0.005). CONCLUSIONS: This study supports the hypothesis
      that sensitivity to mutagens increases the risk of neoplastic progression in
      persons with Barrett's esophagus, particularly those with 17p LOH including TP53.

PMID- 17035404
TI  - Evaluation of the 4q32-34 locus in European familial pancreatic cancer.
AB  - BACKGROUND: Familial pancreatic cancer (FPC) describes a group of families where
      the inheritance of pancreatic cancer is consistent with an autosomal-dominant
      mode of inheritance. The 4q32-34 region has been previously identified as a
      potential locus for FPC in a large American family. METHODS: The region was
      allelotyped in 231 individuals from 77 European families using nine
      microsatellite markers, and haplotyping was possible in 191 individuals from 41
      families. Families were selected based on at least two affected first-degree
      relatives with no other cancer syndromes. RESULTS: Linkage to most of the locus
      was excluded based on LOD scores less than -2.0. Eight families were excluded
      from linkage to 4q32-34 based on haplotypes not segregating with the disease
      compared with a predicted six to seven families. Two groups of families were
      identified, which seem to share common alleles within the minimal disease
      associated region of 4q32-34, one group with an apparently earlier age of cancer
      death than the other pancreatic cancer families. Four genes were identified with
      potential tumor suppressor roles within the locus in regions that could not be
      excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA
      sequence analysis of exons of these genes in affected individuals and in
      pancreatic cancer cell lines did not reveal any mutations. CONCLUSION: This locus
      is unlikely to harbor a FPC gene in the majority of our European families.

PMID- 17035405
TI  - 5,10-Methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic
      leukemia risk: a meta-analysis.
AB  - There is evidence supporting a role for 5-10 methylenetetrahydrofolate reductase
      (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more
      robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a
      meta-analysis to reevaluate the association between the two most commonly studied
      MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies
      investigating an association between the C677T or A1298C polymorphisms and risk
      of ALL were included. We applied both fixed-effects and random-effects models to
      combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was
      used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used
      to assess publication bias. The meta-analysis of the C677T polymorphism and risk
      of childhood ALL included 13 studies with a total of 4,894 individuals. Under a
      fixed-effects model, the TT genotype failed to be associated with a statistically
      significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI,
      0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele
      exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45;
      95% CI, 0.26-0.77; P = 0.004). In both cases, no evidence of heterogeneity was
      observed. No association between the A1298C variant and susceptibility to both
      adult and childhood ALL was disclosed. Our findings support the proposal that the
      common genetic C677T polymorphism in the MTHFR contributes to the risk of adult
      ALL, but not to the childhood ALL susceptibility.

PMID- 17035406
TI  - The risk of cancer following hospitalization for infection in infancy: a
      population-based cohort study.
AB  - BACKGROUND: The relation between infections in infancy and subsequent cancer risk
      in children and young adults is controversial. Our aim was to examine this
      association in the Jerusalem Perinatal Study, a population-based cohort
      comprising all offspring from western Jerusalem and surroundings born from 1964
      to 1976. METHODS: Identity numbers of non-malformed singletons with recorded data
      about hospital admission in the 1st year of life (n = 24,554) were linked to the
      Population and Cancer Registries. Person-year incidence rates were calculated for
      the exposed (admitted for infection) and nonexposed (not admitted for infection)
      groups from birth to date of cancer diagnosis, death, or December 31, 2004. We
      used Cox proportional hazards models to adjust for covariates associated with
      hospitalization. RESULTS: The median follow-up was 36 years. Cancer developed in
      283 individuals. Hospitalization for infection was not associated with overall
      cancer risk [risk ratio (RR), 0.88; 95% confidence interval (95% CI), 0.56-1.37].
      The incidence rate for non-Hodgkin's lymphoma was higher in the exposed compared
      with the nonexposed group (RR, 3.46; 95% CI, 1.38-8.68), remaining unchanged
      after controlling for birth weight, gender, and maternal education. Leukemia risk
      was not significantly associated (RR, 0.44; 95% CI, 0.06-3.24) with
      hospitalization for infection. CONCLUSIONS: Hospital admission in the 1st year of
      life due to infection is associated with an increased risk of non-Hodgkin's
      lymphoma. This is consistent with observations that mild immunodeficiencies
      predispose to lymphoma. Survival of infants with subtle immune defects, who may
      have previously succumbed to their infection, may contribute to the increased
      incidence of non-Hodgkin's lymphoma observed over the last 50 years.

PMID- 17035407
TI  - Health status of long-term cancer survivors: results from an Australian
      population-based sample.
AB  - BACKGROUND: Despite considerable knowledge about the effect of cancer during the
      early stages of treatment and survivorship, understanding the longer-term effect
      of cancer has only recently become a priority. This study investigated the health
      implications of longer-term cancer survivorship in an Australian, population
      based sample. METHODS: Using the Australian National Health Survey, 968 longer
      term cancer survivors were identified, along with 5,808 age- and sex-matched
      respondents without a history of cancer. Four measures of health effect were
      compared (quality of life, health status, days out of role, and mental well
      being), using polytomous and logistic regression analyses controlling for other
      selected chronic conditions. These models were applied across both groups
      overall, across groups stratified by presence/absence of cancer, and other
      chronic conditions, as well as by tumor site. RESULTS: Compared with matched
      respondents without cancer, longer-term cancer survivors reported significant
      decrements in health status, days out of role, and mental well-being (all P <
      0.02), but not in quality of life. The likelihood of poor health outcomes
      (including quality of life) was much higher among survivors who also reported
      comorbid chronic conditions. Despite mixed results across tumor site, melanoma
      and prostate cancer survivors fared better across most outcomes. CONCLUSIONS:
      Clear evidence of excess morbidity among Australian longer-term cancer survivors
      seems to be further exacerbated by the presence of comorbid chronic conditions.
      Consistent with recent U.S. studies, these results further support the importance
      of ongoing surveillance of the growing number of cancer survivors worldwide along
      with increased attention to interventions to improve long-term health outcomes.

PMID- 17035408
TI  - Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer
      prevention trial.
AB  - Studies on the relationship between obesity and prostate cancer incidence are
      inconsistent. In part, this inconsistency may be due to a differential effect of
      obesity on low-grade and high-grade cancer or confounding of the association of
      obesity with prostate cancer risk by diabetes. We investigated the associations
      of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data
      were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer
      Prevention Trial who all had cancer presence or absence determined by prostate
      biopsy. Multiple logistic regression was used to model the risk of total prostate
      cancer, and polytomous logistic regression was used to model the risk of low
      grade and high-grade prostate cancer. Compared with men with body mass index <
      25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95%
      confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate
      cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of
      high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78;
      95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to
      10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk
      of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk
      of high-grade prostate cancer. Associations of obesity or diabetes with cancer
      risk were not substantially changed by mutually statistical controlling for each
      other. Obesity increases the risk of high-grade but decreases the risk of low
      grade prostate cancer, and this relationship is independent of the lower risk for
      prostate cancer among men with diabetes.

PMID- 17035409
TI  - Perinatal factors and mortality from breast cancer.
AB  - Inverse associations have been reported between birthweight and subsequent
      mortality from circulatory disease and diabetes among women. In the current
      study, we assessed whether perinatal factors were associated with mortality from
      breast cancer. This follow-up study consists of breast cancer cases who
      participated in two population-based case-control studies of breast cancer in
      women under age 45 years conducted between 1983 and 1992 in three western
      Washington counties. This analysis is restricted to the 1,024 cases or their
      proxies who completed a supplementary questionnaire on perinatal factors from
      1994 to 1996. The mean and median length of follow-up among living cohort members
      were 153 and 148 months, respectively. Relative to women who were firstborn,
      women who were born second or higher in the birth order seemed to have lower
      mortality from breast cancer [hazard ratio (HR), 0.2; 95% confidence interval
      (95% CI), 0.2-0.3]. In contrast, maternal age of > or =35 years (HR, 1.7; 95% CI,
      1.1-2.8) was associated with higher breast cancer mortality relative to a
      maternal age of <25 years. Birth order modified the effect of maternal age on
      mortality from breast cancer (P = 0.03). There was evidence of increased breast
      cancer mortality for birthweight of > or =4,000 g (HR, 1.8; 95% CI, 1.0-3.1) and
      twin membership (HR, 2.5; 95% CI, 1.0-6.2). The protective effect of being born
      second or higher in the birth order against breast cancer mortality regardless of
      maternal age is striking and needs to be confirmed in future studies.

PMID- 17035410
TI  - No association between 25-hydroxyvitamin D and mammographic density.
AB  - There is increasing evidence that vitamin D may protect against breast cancer.
      Some studies have suggested that dietary and supplemental vitamin D is associated
      with reduced mammographic density, which is highly associated with breast cancer
      risk, although this evidence is not entirely consistent. We investigated a
      possible association between circulating 25-hydroxyvitamin D (25OHD), the best
      indicator of vitamin D status, and quantitative mammographic density in the
      Minnesota Breast Cancer Family Study. Mean values of mammographic density (both
      percent and area densities) and circulating levels of 25OHD were compared across
      categories of covariates using ANOVA. Models were adjusted for age and body mass
      index, as well as other covariates, and also stratified by dietary calcium
      intake, menopause, and season. Serum, mammographic density, and questionnaire
      data were available from 487 women [133 premenopausal and 354 postmenopausal;
      mean age, 56.4 years (range, 27-85 years)] without breast cancer, and for 73%,
      the blood was drawn within 1 year of their mammogram. No evidence was found for
      an association between 25OHD and either percent density or total dense area.
      There was also no evidence for any association when the data were stratified by
      season of sample (winter and summer) or menopause. However, both percent density
      and dense area were lowest among those in the highest vitamin D quartile with
      calcium intake above the median. Unlike some previous reports, vitamin D does not
      seem to be related to mammographic density in this cohort.

PMID- 17035411
TI  - Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast
      cancer risk: the multiethnic cohort.
AB  - Collective evidence suggests that the insulin-like growth factor (IGF) system
      plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are
      the principal regulatory molecules that modulate IGF-I bioavailability in the
      circulation and tissues. To examine whether inherited differences in the IGFBP1
      and IGFBP3 genes influence prostate and breast cancer susceptibility, we
      conducted two large population-based association studies of African Americans,
      Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess
      the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3
      exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure
      that we had identified all common missense variants and (b) characterized the
      linkage disequilibrium patterns and common haplotypes by genotyping 36 single
      nucleotide polymorphisms (SNP) spanning 71 kb across the loci ( approximately 20
      kb upstream and approximately 40 kb downstream, respectively) in a panel of 349
      control subjects of the five racial/ethnic groups. No new missense SNPs were
      found. We identified three regions of strong linkage disequilibrium and selected
      a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1
      and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association
      between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with
      prostate and breast cancer risk in two large case-control studies nested within
      the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases
      (largely postmenopausal)/controls = 1,615/1,962]. We observed no strong
      associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either
      prostate or breast cancer risk. Our results suggest that common genetic variation
      in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast
      cancer susceptibility.

PMID- 17035412
TI  - Fruit and vegetable consumption and incidence of gastric cancer: a prospective
      study.
AB  - BACKGROUND: Whether fruit and vegetable consumption may confer protection from
      gastric cancer remains controversial. METHODS: We prospectively investigated the
      association between consumption of fruits and vegetables and the incidence of
      gastric cancer among participants from two population-based cohort studies:
      36,664 women in the Swedish Mammography Cohort and 45,338 men in the Cohort of
      Swedish Men. Participants completed a food-frequency questionnaire in 1997 and
      were followed up for cancer incidence through June 2005. Cox proportional hazards
      models were used to estimate multivariate hazard ratios (HR) and 95% confidence
      intervals (95% CI). RESULTS: During a mean follow-up of 7.2 years, we ascertained
      139 incident cases of gastric cancer. Vegetable consumption was inversely
      associated with risk of gastric cancer, whereas no significant association was
      observed for fruit consumption. After controlling for age and other risk factors,
      women and men who consumed > or =2.5 servings/d of vegetables had a HR of 0.56
      (95% CI, 0.34-0.93) for developing gastric cancer compared with those who
      consumed <1 serving/d. The respective HR for fruit consumption was 0.86 (95% CI,
      0.52-1.43). Among specific subgroups of vegetables, consumption of green leafy
      vegetables and root vegetables was inversely associated with risk of gastric
      cancer; the multivariate HRs comparing > or =3 servings/wk with <0.5 serving/wk
      were 0.64 (95% CI, 0.42-0.99) for green leafy vegetables and 0.43 (95% CI, 0.27
      0.69) for root vegetables. CONCLUSIONS: Frequent consumption of vegetables may
      reduce the risk of gastric cancer.

PMID- 17035413
TI  - Death receptor 4 variants and colorectal cancer risk.
AB  - The tumor necrosis factor-related apoptosis-inducing ligand receptor modulates
      apoptotic response by binding to the proapoptotic death receptor 4 (DR4).
      Perturbed apoptosis due to missense alterations in the candidate tumor suppressor
      gene DR4 leads to deregulated cell proliferation and cancer predisposition.
      Recent studies have discussed the association of DR4 variants with cancer risk.
      We evaluated, for the first time, the role of the Thr(209)Arg (626C>G) and
      Glu(228)Ala (683A>C) polymorphisms on colorectal cancer risk by genotyping 659
      incident cases and 607 healthy controls drawn from the German population-based
      Darmkrebs: Chancen der Verhutung durch Screening (DACHS) study. Whereas DR4
      Glu(228)Ala was not associated with colorectal cancer, Thr(209)Arg heterozygotes
      were at a significantly decreased colorectal cancer risk [odds ratio (OR), 0.73;
      95% confidence interval (95% CI), 0.54-0.97]. Stratification according to sex and
      age exhibited a significant association of Thr(209)Arg with a decreased risk for
      male heterozygotes (OR, 0.68; 95% CI, 0.46-0.99) and for Arg(209) carriers > or
      =65 years of age (OR, 0.65; 95% CI, 0.46-0.92) as well as an enhanced risk for
      female Ala(228) carriers in a allele dose-dependent manner (P(trend) = 0.01).
      Subsite analysis revealed a protective effect of Thr(209)Arg for rectal cancer
      risk (OR, 0.67; 95% CI, 0.48-0.95) and a significant risk increase for Ala(228)
      carriers with advanced colorectal cancer stages (P(trend) = 0.04). Haplotype
      analysis revealed a 2.4-fold risk for carriers of the rare 626C-683C haplotype
      (1% prevalence in the general population; OR, 2.37; 95% CI, 0.98-5.76). The score
      statistic yielded an empirical P of 0.03 of the haplotype-specific test for 626C
      683C based on 20,000 simulations, suggesting that DR4 626C-683C may affect
      colorectal cancer predisposition.

PMID- 17035414
TI  - Total magnesium intake and colorectal cancer incidence in women.

PMID- 17035415
TI  - No association between serum insulin-like growth factor (IGF)-I, IGF-binding
      protein-3, and lung cancer risk.

PMID- 17035416
TI  - Maternal androgen and estrogen concentrations are not associated with blood
      pressure changes in uncomplicated pregnancies.
AB  - Systolic blood pressure increase between the second and third trimester of
      pregnancy has been associated with a substantially reduced maternal breast cancer
      risk, and it has been suggested that elevated androgens mediate the association.
      Androgen and estrogen concentrations were measured in maternal serum collected in
      86 uncomplicated, singleton pregnancies. Overall, there were no consistent or
      statistically significant patterns of association between the hormones and
      systolic, diastolic, or mean arterial blood pressure or blood pressure change
      between trimesters. Results were similar with adjustment for factors related to
      the hormones. These data are not consistent with the hypothesis that elevated
      androgen concentrations mediate the observed reduction in maternal breast cancer
      risk associated with increases in blood pressure over the pregnancy.

PMID- 17035417
TI  - "Vital" sign?

PMID- 17035418
TI  - Pulmonary hypertension trials: current end points are flawed, but what are the
      alternatives?

PMID- 17035419
TI  - Lung cancer: family history matters.

PMID- 17035420
TI  - Did Lady Windermere have cystic fibrosis?

PMID- 17035421
TI  - Optimal therapy for methicillin-resistant Staphylococcus aureus pneumonia: what
      is the best dosing regimen?

PMID- 17035422
TI  - Emergency department hypotension predicts sudden unexpected in-hospital
      mortality: a prospective cohort study.
AB  - OBJECTIVE: The prevalence and prognostic significance of nontraumatic hypotension
      measured in the emergency department (ED) have not been studied. We hypothesized
      that ED hypotension confers risk of in-hospital mortality. DESIGN: Prospective
      cohort study. SETTING: Large urban ED with 115,000 visits per year. PARTICIPANTS:
      Nontrauma ED patients aged > 17 years admitted to the hospital were prospectively
      identified on a random sample of 24-h blocks during 2004 to 2005. "Exposures" had
      any systolic BP (SBP) < 100 mm Hg in the ED; "nonexposures" all had SBP >/= 100
      mm Hg in the ED. Deaths were classified as sudden and unexpected by independent
      observers using explicit criteria. OUTCOME MEASURES: Mortality rates were
      compared with confidence intervals (CIs), Kaplan-Meier survival curves, and
      multivariate logistic regression. RESULTS: A total of 4,790 patients were
      enrolled during the study period, with 887 patients (19%) in the exposure group.
      Exposures were more likely to die in the hospital compared with nonexposures (8%
      vs 3%; 95% CI for difference of 5%, 4 to 8%). Exposures were more likely to have
      sudden and unexpected death compared with nonexposures (2% vs 0.2%, 95% CI for
      difference of 1.8%, 1 to 3%). Kaplan-Meier estimates showed increased mortality
      in the exposure group at all time points (log-rank test, p < 0.001). Multivariate
      logistic regression revealed exposure to hypotension as an independent predictor
      of in-hospital mortality (odds ratio, 2.0; 95% CI, 1.3 to 2.8). CONCLUSION:
      Nontraumatic hypotension was documented in 19% of a random sample of ED patients
      admitted to the hospital. Patients exposed to hypotension had a significantly
      increased risk of death during hospitalization.

PMID- 17035423
TI  - Predictors of mortality for methicillin-resistant Staphylococcus aureus health
      care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic
      indices.
AB  - OBJECTIVE: The goal of this investigation was to determine whether vancomycin
      pharmacokinetic indexes (eg, serum trough concentrations or area under the
      concentration curve [AUC] values) were associated with mortality for patients
      with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant
      Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center,
      observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban
      teaching facility. PATIENTS: Adult patients requiring hospitalization who were
      identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures.
      INTERVENTIONS: Retrospective data collection from automated hospital,
      microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred
      two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two
      patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin
      trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p =
      0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p =
      0.941) did not differ between survivors and nonsurvivors. The stratification of
      the vancomycin trough concentrations and AUC values yielded no relationship with
      hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin
      trough concentrations or AUC values correlated with hospital outcome. Based on
      these results, aggressive dosing strategies for vancomycin (eg, trough
      concentrations of > 15 microg/mL) may not offer any advantage over traditional
      dose targets (range, 5 to 15 microg/mL).

PMID- 17035424
TI  - Agreement between quantitative cultures of postintubation tracheal aspiration and
      plugged telescoping catheter, protected specimen brush, or BAL for the diagnosis
      of nosocomial pneumonia.
AB  - BACKGROUND: The diagnosis of ventilator-associated pneumonia relies on protected
      specimen brush (PSB), BAL, and plugged telescoping catheter (PTC) procedures. In
      the particular setting of nosocomial pneumonia (NP) occurring in non-mechanically
      ventilated patients, no consensus exists on their use. When mechanical
      ventilation (MV) becomes mandatory, postintubation tracheal aspiration (PITA)
      could be a simple, fast, and cheap diagnostic tool. Our aim was to compare the
      diagnostic accuracy of PITA to that of PSB, BAL, or PTC in patients requiring MV
      for suspected NP. METHODS: Patients with a prior hospital stay of > or = 48 h who
      required MV for suspicion of NP were prospectively enrolled in the study. PITA
      was performed by sterile suction. Within 2 h, pulmonary samples were obtained by
      PSB, BAL, or blinded PTC, which are referred to hereafter as "reference methods"
      (RMs). The definite diagnosis of NP was made using a composite item of clinical,
      radiologic, and bacteriologic (ie, blood or pleural fluid cultures) patterns. The
      agreement between the quantitative microbiological results obtained with PITA and
      those of the RMs was assessed by the kappa-statistic. The sensitivity,
      specificity, and positive and negative likelihood ratios of PITA and RMs were
      calculated taking the definite diagnosis of NP as the reference. RESULTS: There
      were 44 cases (63.8%) of confirmed NP. The kappa-statistic was 0.71. The
      sensitivity, specificity, and positive and negative likelihood ratios were 77%,
      84%, 4.80, and 0.27, respectively, for PITA, and 75%, 88%, 6.25, and 0.28,
      respectively, for RMs. CONCLUSIONS: PITA may be a reliable alternative to RMs in
      the particular setting of NP in newly mechanically ventilated patients.

PMID- 17035425
TI  - Hyperchloremic acidosis increases circulating inflammatory molecules in
      experimental sepsis.
AB  - RATIONALE: Hyperchloremic acidosis is common in the critically ill and is often
      iatrogenic. We have previously shown that hyperchloremic acidosis increases
      nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7
      cells. However, evidence that hyperchloremic acidosis leads to increased
      inflammation in vivo has been limited to nitric oxide. OBJECTIVES: To determine
      if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase
      circulating inflammatory mediator levels in an experimental model of severe
      sepsis in rats. METHODS: Eighteen hours after inducing lethal sepsis by cecal
      ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized
      animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N
      HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L,
      respectively. In group 1, we infused a similar volume of lactated Ringer
      solution. In all groups infusion continued 8 h or until the animal died.
      MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gases, whole-blood
      lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10
      levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared
      to group 1, animals in groups 2 and 3 exhibited greater increase in all three
      cytokines, with the greatest increases seen with severe acidosis. CONCLUSION:
      Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by
      HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in
      normotensive septic rats.

PMID- 17035426
TI  - Association between lung cancer incidence and family history of lung cancer: data
      from a large-scale population-based cohort study, the JPHC study.
AB  - STUDY OBJECTIVES: To clarify the possibility of a hereditary predisposition to
      lung cancer, we investigated the association between a family history of lung
      cancer and subsequent risk of lung cancer in a large-scale, population-based
      cohort study. DESIGN: We investigated 102,255 middle-aged and older Japanese
      subjects (48,834 men and 53,421 women) with 13-year follow-up. A total of 791
      cases of lung cancer were newly diagnosed during the follow-up period. RESULTS: A
      family history of lung cancer in a first-degree relative was associated with a
      significantly increased risk of lung cancer (hazard ratio [HR], 1.95; 95%
      confidence interval [CI], 1.31 to 2.88). The association was stronger in women
      than in men (HR, 2.65; 95% CI, 1.40 to 5.01 and HR, 1.69; 95% CI, 1.03 to 2.78,
      respectively), and in never-smokers than in current smokers (HR, 2.48; 95% CI,
      1.27 to 4.84 and HR, 1.73; 95% CI, 0.99 to 3.00, respectively). In addition,
      family history was more strongly associated with the risk of squamous cell
      carcinoma than with other histologic types (HR, 2.79; 95% CI, 1.37 to 5.68),
      while no clear increase in risk was observed in adenocarcinoma and small cell
      carcinoma. A family history of overall cancer was not associated with an
      increased risk of lung cancer. CONCLUSIONS: These results suggest that those with
      a family history of lung cancer are more likely to acquire lung cancer
      themselves.

PMID- 17035427
TI  - Unique characteristics of systemic sclerosis sine scleroderma-associated
      interstitial lung disease.
AB  - STUDY OBJECTIVES: To describe the characteristics of systemic sclerosis sine
      scleroderma (ssSSc)-associated interstitial lung disease (ILD) presenting as
      idiopathic interstitial pneumonia (IIP). DESIGN: Retrospective review of six
      patients with ssSSc-associated ILD diagnosed after referral for evaluation of
      IIP. MEASUREMENT AND RESULTS: All patients were white, their mean age was 56
      years (range, 37 to 86), and gender was evenly divided. Sclerodactyly, skin
      thickening, and digital edema were absent in all patients. All patients had
      scattered telangiectasia, and four patients had Raynaud phenomenon with abnormal
      nailfold capillaroscopy findings. All described gastroesophageal reflux, and
      three patients had esophageal dysmotility by esophagography. All had restrictive
      pulmonary physiology and a reduced diffusion capacity. High-resolution CT
      revealed nonspecific interstitial pneumonia (NSIP) or usual interstitial
      pneumonia (UIP) radiographic patterns. Of the three patients who underwent
      surgical lung biopsy, two patients had NSIP and one patient had UIP pathologic
      patterns. Five patients had asymptomatic pericardial effusions and elevated
      pulmonary artery pressures by echocardiography. All patients had nucleolar
      staining anti-nuclear antibodies (ANAs), and one patient was anti-Scl-70
      positive. All five anti-Scl-70-negative patients were anti-Th/To positive, and
      the anti-Scl-70-positive patient was anti-Th/To negative. CONCLUSIONS: In the
      presentation of an IIP, the presence of a nucleolar-staining ANA, telangiectasia,
      Raynaud phenomenon with abnormal capillaroscopy findings, gastroesophageal
      reflux, or pericardial disease suggests underlying systemic sclerosis. These
      findings should aid clinicians in the evaluation and treatment of patients with
      otherwise undefined ILD.

PMID- 17035428
TI  - Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Recent evidence has shown that several chemokines--including those
      involved in angiogenesis--have been implicated in the pathogenesis of idiopathic
      pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences
      could be attributed to distinct angiogenic and angiostatic profiles. This
      hypothesis was investigated by estimating the levels of three angiogenic
      chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating
      protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines
      (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein
      [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL
      fluid (BALF). METHODS: We studied prospectively 20 patients with sarcoidosis
      (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age,
      68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years;
      range, 26 to 60 years). RESULTS: The GRO-a serum and BALF levels of IPF patients
      were found significantly increased in comparison with healthy subjects (799 pg/mL
      vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively)
      and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs
      214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in
      IPF patients were significantly higher compared with sarcoidosis patients (191
      pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03],
      respectively). MIG serum levels in IPF patients were found significantly
      upregulated in comparison with sarcoidosis patients and healthy control subjects.
      However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112
      pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in
      sarcoidosis patients compared with IPF patients. CONCLUSIONS: Our data suggest
      distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential
      different role of CXC chemokines in the local immunologic response in IPF and
      pulmonary sarcoidosis.

PMID- 17035429
TI  - Fatigue is associated with quality of life in sarcoidosis patients.
AB  - BACKGROUND: Fatigue is one of the core symptoms of sarcoidosis patients. Although
      it is known that fatigue affects quality of life (QOL) in other patient groups,
      this relationship has never been studied in sarcoidosis patients using a reliable
      and valid fatigue scale and a multidimensional QOL instrument. The present cross
      sectional study among sarcoidosis patients attempts to gain more insight into
      this relationship. METHODS: One hundred forty-five sarcoidosis patients of an
      outpatient pulmonary clinic in Zagreb, Croatia, completed the Fatigue Assessment
      Scale (FAS) and QOL scale (World Health Organization Quality of Life Assessment
      Instrument-100) between January 2002 and May 2004. Clinical parameters were
      derived from the patients' medical files. RESULTS: Tired patients reported a
      worse QOL in all domains and fatigue negatively predicted all QOL domains by
      means of multivariate regression analyses (beta values ranging from - 0.31 to -
      0.64, all p < 0.001). Corticosteroid use was not a predictor of QOL. Diffusion
      capacity of the lung for carbon monoxide was the only clinical parameter
      associated with a QOL domain, namely level of independence. CONCLUSIONS: Fatigue
      was related to all QOL domains. Furthermore, standard clinical parameters were
      not associated with fatigue or QOL, except for level of independence. If these
      results were to be replicated in a prospective study, fatigue as measured by the
      FAS could be a good indicator of QOL in sarcoidosis patients.

PMID- 17035430
TI  - Prospective analysis of cystic fibrosis transmembrane regulator mutations in
      adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection.
AB  - BACKGROUND: Bronchiectasis and pulmonary infection with nontuberculous
      mycobacteria (NTM) may be associated with disease-causing mutations in the cystic
      fibrosis transmembrane regulator (CFTR). METHODS: Fifty adult patients at
      Stanford University Medical Center with a diagnosis of bronchiectasis and/or
      pulmonary NTM infection were prospectively characterized by sweat chloride
      measurement, comprehensive mutational analysis of CFTR, and sputum culture
      results. RESULTS: A de novo diagnosis of cystic fibrosis (CF) was established in
      10 patients (20%). Patients with CF were more likely than those without CF to
      have mucus plugging seen on chest high-resolution CT, and women with a CF
      diagnosis were thinner, with a significantly lower mean body mass index than the
      non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50%
      prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of
      CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%).
      The frequency of CFTR mutations was elevated above that expected in the general
      population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T
      (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X,
      R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were
      identified: A394V, F650L, and C1344S. CONCLUSIONS: Mutations in CFTR that alter
      RNA splicing and/or functional chloride conductance are common in this
      population, and are likely to contribute to the susceptibility and pathogenesis
      of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation
      for disease cause should be undertaken in this clinical context.

PMID- 17035431
TI  - The effect of 1 week of continuous positive airway pressure treatment in
      obstructive sleep apnea patients with concomitant gastroesophageal reflux.
AB  - STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) have a very high
      incidence of gastroesophageal reflux (GER). Previous studies have shown that the
      use of continuous positive airway pressure (CPAP) reduces the frequency of reflux
      events, but these studies only assessed the effect of a single night of
      treatment. The aim of this study was to assess the effect of 1 week of CPAP
      treatment on reflux in patients with OSA and GER. DESIGN: Sixteen patients with
      OSA and GER were recruited. Polysomnography followed by 24-h, continuous
      esophageal pH monitoring were performed at baseline. Patients with an apnea
      hypopnea index (AHI) > 20/h and 24-h acid contact time (ACT) of at least 6% were
      included. As part of the polysomnography-qualifying evaluation, all patients
      underwent CPAP titration to reduce the AHI to < 10/h. Patients were then sent
      home receiving nasal CPAP for 1 week; after 1 week, esophageal pH monitoring was
      repeated while receiving CPAP. MEASUREMENTS AND RESULTS: The AHI fell from 63.3
      +/- 38.5 to 3.2 +/- 2.2/h (mean +/- SD) [p < 0.001]. Total ACT fell from 13.9 +/-
      11.6 to 5.6 +/- 2.7% (p < 0.001). The upright ACT was reduced from 12.4 +/- 6.8
      to 6.8 +/- 3.8% (p = 0.01), and the supine (during the sleeping interval) ACT was
      reduced from 16.3 +/- 18.8 to 3.8 +/- 7.6% (p < 0.01). Eighty-one percent of the
      patients had a reduction in supine ACT to within the normal range (< 4%).
      CONCLUSIONS: In OSA patients with significant heartburn complaints, CPAP would
      appear to be an efficacious approach to the treatment of both disorders.

PMID- 17035432
TI  - Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea
      syndrome.
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a known risk factor for
      hypertension in adults. This relationship is less clear in childhood OSAS.
      OBJECTIVE: This study examined the relationship between OSAS and 24-h ambulatory
      BP (ABP), a more accurate assessment than casual BP, in children with snoring.
      METHODS: Snoring children aged 6 to 15 years who underwent polysomnography in the
      sleep laboratory were recruited. MEASUREMENT: Twenty-four-hour ABP monitoring was
      initiated a few hours before polysomnography. The children were classified into
      two groups: a high apnea-hypopnea index (AHI) group (obstructive AHI > 5/h), and
      a low-AHI group (AHI < or = 5/h). Mean sleep, wake, and 24-h systolic BP (SBP)
      and diastolic BP (DBP) were recorded. A child was considered a "nondipper" if his
      or her mean SBP and DBP did not decrease by >/= 10% during sleep. RESULTS: Ninety
      six children (mean age +/- SD, 9.4 +/- 2.8 years) were recruited. Forty-one
      children were obese. When awake, the high-AHI group children had a significantly
      higher SBP. When asleep, both SBP and DBP were higher in the high-AHI group. Age,
      body mass index (BMI) z score, and desaturation index (DI) were significant
      predictors for elevated sleep DBP. BMI z score was the only significant predictor
      for wake and sleep SBP. Sixteen children (17%) had hypertension, and all were
      nondippers. Obese children in the high-AHI group had a significantly higher
      prevalence of hypertension than obese children in the low-AHI group. This
      relationship was not found in nonobese children. CONCLUSION: The current study
      shows that increased DI contributed to the elevation of sleep DBP elevation.

PMID- 17035433
TI  - Pressure-relief continuous positive airway pressure vs constant continuous
      positive airway pressure: a comparison of efficacy and compliance.
AB  - OBJECTIVES: To compare polysomnographic data and compliance in sleep apnea
      patients receiving continuous positive airway pressure (CPAP) and pressure-relief
      CPAP (PRCPAP) [C-flex; Respironics; Murrysville, PA] as first treatment in the
      sleep laboratory and subsequently at home. DESIGN: A prospective, randomized,
      crossover design was used in the sleep laboratory, and a prospective randomized
      design was used at home. PATIENTS: Data were collected from 52 sleep apnea
      patients for whom CPAP was used for the first time. INTERVENTIONS: Treatment with
      constant CPAP and PRCPAP. MEASUREMENTS AND RESULTS: Patients with a first-time
      diagnosis of obstructive sleep apnea syndrome (OSAS) underwent conventional CPAP
      titration. Thereafter, polysomnography was performed at the titrated pressure
      using both the fixed CPAP pressure mode and the PRCPAP mode in a randomized
      crossover approach. The patients were then discharged home for 7 weeks of
      treatment with the last-applied treatment mode, and compliance data were
      established at the end of that time. The average apnea-hypopnea index was 53.3/h
      in the "diagnostic night," 5.8/h with CPAP, and 7.0/h with PRCPAP. The native
      arousal index was 35.2/h, 12.6/h with CPAP, and 12.9/h with PRCPAP (not
      significant [NS]). The central apnea index was 0.7/h with CPAP and 1.2/h with
      PRCPAP (p < 0.05). Compliance after 7 weeks was, on average, 9.4 min longer with
      PRCPAP than with CPAP (NS). Evaluation of a 13-item questionnaire showed scores
      of 16.4 for PRCPAP and 18.1 for constant CPAP (NS) [the fewer the complaints, the
      lower the score]. With regard to oral dryness, the score with PRCPAP (1.4) was
      significantly lower than with constant CPAP (1.9) [p < 0.05]. This difference was
      no longer detectable after 7 weeks. CONCLUSION: In terms of the effectiveness in
      treating obstructive sleep apnea, PRCPAP and constant CPAP are comparable. During
      the first night of treatment, patients receiving PRCPAP had less dryness of
      mouth; over a period of 7 weeks, this difference disappeared. Nightly use of the
      device was comparable in both groups. PRCPAP is therefore a new ventilation mode
      that enables effective treatment of OSAS patients. Further studies should be done
      to investigate the effects of expiratory pressure lowering in low-compliance
      patients and patients requiring CPAP > 9 cm H(2)O or experiencing dry mouth with
      CPAP.

PMID- 17035434
TI  - Abnormalities of the bronchial arteries in asthma.
AB  - STUDY OBJECTIVES: The bronchial arteries supply systemic blood to the airways,
      tracheobronchial lymph nodes, and nerves. Their structure has not been studied in
      patients with asthma. DESIGN: Case-control study of pathologic changes of
      bronchial arteries in asthma. PARTICIPANTS AND METHODS: Postmortem lungs were
      examined from three case groups: (1) fatal asthma (n = 12), death due to asthma;
      (2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes;
      and (3) nonasthmatic control subjects (n = 12), no history of asthma and death
      due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1
      to 1.0 mm, the areas of lumen, intima, and media were measured and compared
      between case groups. RESULTS: There were no significant differences in artery
      size (outer diameter) or in medial area between the three groups. In the two
      asthma groups, the intimal area was increased (p < 0.05), with a corresponding
      decrease in luminal area compared with the control group. There was a significant
      effect of gender, age, and smoking on intimal area. In the asthma cases, the area
      of bronchial artery intima was related to duration of asthma (p < 0.05), and this
      increase was associated with smooth muscle proliferation, reduplication, and
      calcification of the elastica, but not with inflammatory cell infiltration.
      CONCLUSIONS: While the pathophysiologic significance of these changes is
      uncertain, the relation to duration of asthma, age, and smoking suggests a
      secondary response to chronic airway disease.

PMID- 17035435
TI  - Depressive symptoms and adherence to asthma therapy after hospital discharge.
AB  - STUDY OBJECTIVES: To evaluate the effect of depressive symptoms on adherence to
      therapy after discharge in patients hospitalized for asthma exacerbations.
      DESIGN: Prospective cohort study in which depressive symptoms were assessed
      during hospitalization and use of asthma medications was electronically monitored
      for 2 weeks after discharge. SETTING: Inner-city academic hospital in Baltimore,
      MD. PATIENTS: Patients were 59 adults with a mean age of 43.2 +/- 10.9 years (+/-
      SD), who were mostly female (64%), African American (80%), and were hospitalized
      for an asthma exacerbation. MEASUREMENT AND RESULTS: Depressive symptoms were
      assessed with the Center for Epidemiological Studies-Depression scale. Electronic
      monitors were used to evaluate inhaled corticosteroid and oral corticosteroid use
      for up to 2 weeks after discharge. Forty-one percent of patients had high levels
      of depressive symptoms. Mean adherence to therapy was significantly lower in
      patients with (vs without) high levels of depressive symptoms (60 +/- 26% vs 74
      +/- 21%, p + 0.02). Even after controlling for age, gender, and education,
      depressive symptoms were a significant and independent predictor of poorer
      adherence. High levels of depressive symptoms were associated with a 11.4-fold
      increase (95% confidence interval, 2.2 to 58.2) in the odds of poor adherence to
      therapy after adjustment for potential confounders. CONCLUSIONS: Depressive
      symptoms are common in inner-city adults hospitalized for asthma exacerbations
      and identify a subset of patients at high risk for poor adherence to asthma
      therapy after discharge. Further research is needed to determine if screening for
      and treating depression improves adherence and asthma outcomes in this
      population.

PMID- 17035436
TI  - What is worse for asthma control and quality of life: depressive disorders,
      anxiety disorders, or both?
AB  - BACKGROUND: The high burden of asthma appears to be related to poor asthma
      control. Although previous studies have reported associations between depressive
      disorders (DDs) and anxiety disorders (ADs) and worse asthma control and quality
      of life, the relative impact of these disorders on asthma control and quality of
      life has not been explored. This study evaluated the relative impact of having a
      DD and/or AD on asthma control and quality of life. METHOD: Five hundred four
      consecutive adults with confirmed, physician-diagnosed asthma underwent a brief,
      structured psychiatric interview using the Primary Care Evaluation of Mental
      Disorders. Asthma control and asthma-related quality of life were assessed using
      the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life
      Questionnaire (AQLQ). All patients underwent standard spirometry. RESULTS: Thirty
      one percent of patients (n = 157) met the diagnostic criteria for one or more
      psychiatric disorders (8% had DD only, 12% had AD only, and 11% had both).
      Analyses revealed independent effects for DDs on total ACQ scores (p < 0.01), and
      for DDs and ADs on total AQLQ scores and all four AQLQ subscales (p < 0.05).
      There were no interaction effects. CONCLUSIONS: Results suggest that DDs and ADs
      are associated with worse asthma-related quality of life, but only DDs are
      associated with worse asthma control. Interestingly, having both a DD and an AD
      did not confer additional risk for worse asthma control or quality of life.
      Physicians may want to consider the differential impact of negative mood states
      when assessing levels of asthma control and quality of life.

PMID- 17035437
TI  - Increase in concentration of soluble CD86 after segmental allergen challenge in
      patients with allergic asthma.
AB  - STUDY OBJECTIVE: To investigate the effects of segmental allergen challenge on
      the concentration of soluble CD86 (sCD86) in BAL fluids in patients with allergic
      asthma. METHODS: BAL fluid and peripheral blood were collected at baseline, 24 h
      after segmental saline solution or allergen challenge by fiberoptic bronchoscopy
      and venepuncture, respectively, from 10 patients with allergic asthma. Total and
      differential cell counts in BAL fluid were performed, and sCD86 levels in both
      BAL fluid and serum were measured by enzyme-linked immunosorbent assay. RESULTS:
      In allergic asthmatics, there was no significant increase in BAL sCD86
      concentrations after saline solution challenge (median, 2.0 IU/L; 25th to 75th
      percentiles, 0 to 3.4) compared with baseline control subjects (median, 1.2 IU/L;
      25th to 75th percentiles, 0 to 3.6 IU/mL; p = 0.735); however, sCD86
      concentrations were significantly elevated after allergen challenge (median, 8.1
      IU/L; 25th to 75th percentiles, 4.4 to 17.0 IU/mL; p < 0.001). The concentrations
      of sCD86 in BAL fluid after allergen challenge exceeded levels that could be
      accounted for passive transudation from the circulation, based on the magnitude
      of increases in BAL albumin concentrations. CONCLUSIONS: These data indicate that
      allergen challenge results in a significant local accumulation of sCD86 within
      the airways, and that the local release of sCD86 may play a role in allergen
      induced inflammatory processes in the asthmatic airways.

PMID- 17035438
TI  - Evaluation of asthma with hyperpolarized helium-3 MRI: correlation with clinical
      severity and spirometry.
AB  - BACKGROUND: Accurate characterization of asthma severity is difficult due to the
      variability of symptoms. Hyperpolarized helium-3 MRI (H(3)HeMR) is a new
      technique in which the airspaces are visualized, depicting regions with airflow
      obstruction as "ventilation defects." The objective of this study was to compare
      the extent of H(3)HeMR ventilation defects with measures of asthma severity and
      spirometry. METHODS: Patients with a physician diagnosis of asthma and normal
      control subjects underwent H(3)HeMR. For each person, the number and size of
      ventilation defects were scored and the average number of ventilation defects per
      slice (VDS) was calculated. The correlations of the imaging findings with
      measures of asthma severity and spirometry were determined. RESULTS: There were
      58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13;
      moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control
      subjects. Mean +/- SE VDS for asthmatics was significantly greater than for
      control subjects (0.99 +/- 0.15 vs 0.26 +/- 0.22, p = 0.004). Among asthmatics,
      VDS was significantly higher for the group with moderate-persistent and severe
      persistent disease than for the group with mild-intermittent and mild-persistent
      disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly
      with FEV(1)/FVC (r = - 0.51, p = 0.002), forced expiratory flow between 25% and
      75% from the beginning of FVC (FEF(25-75%)) percentage of predicted for height,
      sex, and race (%predicted) [r = - 0.50, p = 0.001], and FEV(1) %predicted (r = -
      0.40, p = 0.002), but not with FVC %predicted (r = - 0.26, p = 0.057) and peak
      expiratory flow %predicted (r = - 0.16, p = 0.231). Many asthmatics had an
      elevated VDS, but their spirometric indexes, except FEF(25%-75%), were normal.
      Most ventilation defects were < 3 cm in size for all asthmatics. In the group of
      patients with moderate-to-severe persistent asthma, there were more defects > or
      =3 cm than in the group with mild-intermittent and mild-persistent disease (p =
      0.021). CONCLUSIONS: Regional changes of airflow obstruction in asthmatics
      depicted by H(3)HeMR correlate with measures of asthma severity and spirometry.

PMID- 17035439
TI  - Room air entrainment during beta-agonist delivery with heliox.
AB  - Studies of the efficacy of heliox in patients with severe asthma have shown mixed
      results. Among the factors that are responsible for variable outcomes, the
      failure of heliox delivery systems to prevent room air entrainment (RAE) during
      beta-agonist delivery is probably the most critical. While keeping the rotameter
      flow rate (FR) of heliox mixed 70:30 to a nebulizer at 10 L/min, the FR of heliox
      from a second gas source to a T-connector (TC) was increased during the delivery
      of the beta-agonist with a conventional T-nebulizer delivery system (TNDS). A
      negative peak inspiratory flow (pneumotachometer reading) or a helium
      concentration of < 70% (quadralizer reading) were indicators of RAE. RAE was
      tested during spontaneous tidal breathing and acute asthma. A rotameter FR of 10
      L/m to the nebulizer with no flow from a second gas source to a TC (conventional
      TNDS) resulted in a significant drop in helium concentration during tidal
      breathing (46.2%) and acute asthma (27.5%) due to RAE. This degree of helium
      dilution can negate the beneficial effects of heliox to lung mechanics almost
      completely. A rotameter FR of 10 L/m each to a nebulizer and a TC resulted in a
      helium concentration 69.8% during tidal breathing (no RAE), but 49% (significant
      RAE) during asthma events. A rotameter FR of 15 L/m (pressure regulator setting,
      100 lbs per square inch) to a TC, while maintaining a rotameter FR of 10 L/m to a
      nebulizer prevented RAE during asthma (helium concentration, 69.9%). Conventional
      TNDS may be used to deliver the beta-agonist with heliox during asthma without
      RAE.

PMID- 17035440
TI  - Dynamic hyperinflation during bronchoconstriction in asthma: implications for
      symptom perception.
AB  - OBJECTIVE: The objective of this study was to examine the relationship between
      respiratory symptom intensity and quality and dynamic lung hyperinflation (DH)
      during induced bronchoconstriction in asthma. PATIENTS AND METHODS: Subjects with
      asthma (n = 116) underwent baseline spirometry and lung volume measurement
      followed by high-dose methacholine challenge testing (MCT) [maximum decrease in
      FEV(1) of 50% from baseline]. Dyspnea intensity (Borg scale) was measured after
      each dose of methacholine. Qualitative descriptors of breathlessness and
      functional residual capacity (FRC) were measured at the doses nearest to the
      provocative concentration of methacholine causing a 20% fall in FEV (PC(20)) and
      at the highest dose of methacholine (maximum response). RESULTS: FEV(1) decreased
      by 24.7 +/- 0.7% (mean +/- SEM) at the dose nearest to PC(20) and by 46.1 +/-
      1.1% at maximum response. Inspiratory capacity decreased by 0.62 +/- 0.04 L at
      the dose nearest to PC(20) and 1.06 +/- 0.06 L at maximum response. The
      descriptor clusters "inspiratory difficulty," "chest tightness," "unsatisfied
      inspiration," and "work" were selected at the dose nearest to PC(20) but were
      more frequently selected at maximum response (p < 0.0001). Individuals who
      reported chest tightness at maximum response had greater airflow obstruction and
      higher FRC (percentage of predicted) than those who did not report chest
      tightness. CONCLUSIONS: Four dominant qualities of dyspnea in asthma (inspiratory
      difficulty, chest tightness, unsatisfied inspiration, and work) were reported
      early in the course of MCT and evolved in parallel, becoming more prevalent at
      maximum response. Significant DH accompanied even mild bronchoconstriction during
      MCT in asthma, making it difficult to separate mechanisms of chest tightness from
      other dominant respiratory sensations.

PMID- 17035441
TI  - Use of inhaled corticosteroids and the risk of fracture.
AB  - BACKGROUND: Previous studies have found an association between the use of inhaled
      corticosteroids and fracture, but the extent to which this association is due to
      inhaled corticosteroids or to related factors, such as the severity of airflow
      obstruction, is disputed. We report a new approach in which we combine data on
      people with airflow obstruction from a large Medical Research Council study of
      the assessment and management of older people in the community with longitudinal
      data from their computerized general practice records. METHODS: Our cohort
      includes 1,671 study participants with a diagnosis of asthma or COPD (mean age,
      80.6 years). We determined the dose-response relationship between inhaled
      corticosteroid exposure and time to first fracture using Cox regression, allowing
      for a wide range of potential confounding factors. RESULTS: During a mean follow
      up period of 9.4 years, 982 patients (59%) received a prescription for an inhaled
      corticosteroid and 187 patients had a fracture. After adjusting for the effects
      of age and gender, we found a dose-related increase in fracture risk with
      exposure to inhaled corticosteroids (rate ratio for mean daily dose > 601 mug,
      2.53; 95% confidence interval [CI], 1.65 to 3.89; overall trend p < 0.0001). The
      results were similar after adjusting for oral corticosteroid exposure, airflow
      obstruction diagnosis, historical fracture, and bronchodilator use (rate ratio,
      4.21; 95% CI, 2.19 to 8.13), and also in the subset of people with no exposure to
      oral corticosteroids (rate ratio, 4.54; 95% CI, 1.23 to 16.74). CONCLUSIONS: Our
      findings provide further evidence that inhaled corticosteroid use is an
      independent risk factor for fracture.

PMID- 17035442
TI  - Effect of rollator use on health-related quality of life in individuals with
      COPD.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of rollator
      use on health-related quality of life in patients with COPD. DESIGN: Randomized
      controlled trial. METHODS: Thirty-one postrehabilitation patients with COPD were
      randomized to receive a rollator (n = 18) or usual care (n = 13) for 8 weeks and
      to record the frequency of rollator use. Outcome measures at baseline, 4 weeks,
      and 8 weeks included the Chronic Respiratory Questionnaire (CRQ) and the 6-min
      walk (6MW). RESULTS: During acute testing, subjects consistently walked further
      when assisted (baseline 6MW: 292 +/- 67 m vs 263 +/- 67 m; 8 weeks: 283 +/- 65 m
      vs 259 +/- 68 m [+/-SD]; p = 0.013). However, provision of a rollator at home was
      not associated with group differences in the CRQ (p > 0.08) or in the unassisted
      6MW (p = 0.4) or the assisted 6MW (p = 0.5). Eight of 18 subjects assigned to the
      rollator group used the rollator less than three times per week. Regular users
      demonstrated a consistent improvement in mastery compared with infrequent users
      (4 weeks: 4.7 +/- 0.6 vs 5.2 +/- 0.8, respectively; 8 weeks: 5.3 +/- 0.8 vs 4.7
      +/- 0.4; p = 0.014). CONCLUSIONS: Despite evidence of effectiveness during acute
      testing, this study did not demonstrate a rollator effect on quality of life or
      exercise capacity when the rollator was provided at home, for a longer period.
      Actual use of a rollator may be an important determinant of its effect.
      Therefore, when prescribing a rollator, health-care professionals should attempt
      to identify those most likely to use it.

PMID- 17035443
TI  - Role of gastroesophageal reflux symptoms in exacerbations of COPD.
AB  - BACKGROUND AND AIMS: The impact of gastroesophageal reflux disease (GERD) on
      exacerbations of COPD has never been evaluated. The aims of this investigation
      were to determine the prevalence of gastroesophageal reflux (GER) symptoms in
      COPD patients and the effect of GER on the rate of exacerbations of COPD per
      year. METHODS: A questionnaire-based, cross sectional survey was performed.
      Subjects were recruited from the outpatient pulmonary clinics at the University
      of Florida Health Science Center/Jacksonville. Included patients had an
      established diagnosis of COPD. Exclusion criteria were respiratory disorders
      other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger
      Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those
      meeting criteria and agreeing to participate were asked to complete the Mayo
      Clinic GERD questionnaire by either personal/telephone interview. Clinically
      significant reflux was defined as heartburn and/or acid regurgitation weekly.
      Other outcome measures noted were frequency and type of COPD exacerbations.
      Statistical analysis was performed using the Fisher exact test for categorical
      data and the independent t test for interval data. RESULTS: Eighty-six patients
      were enrolled and interviewed (mean age, 67.5 years). Male patients accounted for
      55% of the study group. Overall, 37% of patients reported GER symptoms. The mean
      FEV(1) percentage of predicted was similar in those with or without GER. The rate
      of exacerbations of COPD was twice as high in patients with GER symptoms compared
      to those without GER symptoms (3.2/yr vs 1.6/yr, p = 0.02). CONCLUSIONS: The
      presence of GER symptoms appears to be associated with increased exacerbations of
      COPD.

PMID- 17035444
TI  - Epithelial mucin stores are increased in the large airways of smokers with
      airflow obstruction.
AB  - BACKGROUND: Habitual cigarette smoking is associated with chronic mucus
      hypersecretion, but the relationship between mucus abnormalities and airflow
      obstruction in smokers is uncertain. METHODS: We collected bronchial biopsy
      samples and epithelial brushings from 24 smokers with and without airflow
      obstruction and 19 nonsmoking healthy control subjects. Epithelial mucin stores,
      mucin immunostains, and goblet cell morphology were quantified in bronchial
      biopsy samples using stereology, and mucin gene expression was quantified in
      epithelial brushings using real-time reverse transcriptase-polymerase chain
      reaction. RESULTS: Goblet cell size and number were higher than normal in smokers
      (both p < 0.05), leading to a 2.2-fold increase in the volume of stored mucin in
      the epithelium per surface area of basal lamina (1.94 +/- 0.31
      microm(3)/microm(2) vs 4.32 +/- 0.55 microm(3)/microm(2) in control subjects vs
      smokers, p = 0.001). The increase in stored mucin occurred because of an increase
      in MUC5AC (p = 0.018) and despite a decrease in MUC5B (p < 0.0001). Stored mucin
      was significantly higher in the subgroup of smokers with airflow obstruction (p =
      0.029) and correlated with FEV(1)/FVC even when controlling for diffusing
      capacity as a measure of emphysema (p = 0.034). CONCLUSIONS: Epithelial mucin
      stores are increased in habitual smokers because of goblet cell hypertrophy and
      hyperplasia, and the pattern of mucin gene expression is abnormal. The highest
      epithelial mucin stores are found in smokers with airflow obstruction, suggesting
      a mechanistic link between epithelial mucin dysregulation and airflow
      obstruction.

PMID- 17035445
TI  - Impact of a winter respiratory virus season on patients with COPD and association
      with influenza vaccination.
AB  - BACKGROUND: We assessed the effects of an influenza season on patients with COPD.
      Data from 2,215 veterans in a multicenter, randomized, double-blind influenza
      vaccine efficacy study were analyzed for changes in spirometric and functional
      status, comparing patients with laboratory-documented influenza (LDI)-caused
      illness, non-LDI-caused respiratory illness, or no illness, and for association
      with influenza vaccination. METHODS: Patients received either IM trivalent
      inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live
      attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal
      placebo (TP). We performed spirometry, measured the chronic lung disease severity
      index (CLDSI) score to assess functional status and well-being, and tested for
      influenza virus infection. RESULTS: Worsening in FEV(1), percentage of predicted
      FEV(1), and CLDSI score (p < 0.001) was associated with acute respiratory illness
      in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more
      likely to be associated with worsening in FEV(1) and CLDSI score acutely than non
      LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory
      illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be
      associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL,
      1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute
      respiratory illness) to be associated with better CLDSI score at the end of the
      study. Hospitalization was more frequent in patients with acute respiratory
      illness (p < 0.0001). CONCLUSIONS: Acute respiratory illness was associated with
      increased health-care utilization and obstruction to airflow, and worse
      functional status and well-being. At the end of the study, receipt of TC was
      associated with improvement and acute respiratory illness was associated with
      worsening in functional status and well-being.

PMID- 17035446
TI  - Does quality of life of COPD patients as measured by the generic EuroQol five
      dimension questionnaire differentiate between COPD severity stages?
AB  - OBJECTIVE: To assess the discriminative properties of the EuroQol five-dimension
      questionnaire (EQ-5D) with respect to COPD severity according to Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) criteria in a large
      multinational study. METHODS: Baseline EQ-5D visual analog scale (VAS) scores, EQ
      5D utility scores, and St. George Respiratory Questionnaire scores were obtained
      from a subset of patients in the Understanding the Potential Long-term Impact on
      Function with Tiotropium trial, which was a 4-year placebo-controlled trial
      designed to assess the effect of tiotropium on the rate of decline in FEV(1) in
      COPD patients aged > or = 40 years, an FEV(1) of < 70% predicted, an FEV(1)/FVC
      ratio of < or = 70%, and a smoking history of >/= 10 pack-years. RESULTS: A total
      of 1,235 patients (mean post bronchodilator FEV(1), 48.8% predicted) from 13
      countries completed the EQ-5D. The EQ-5D VAS and utility scores differed
      significantly among patients in GOLD stages 2, 3, and 4, also after correction
      for age, sex, smoking, body mass index (BMI), and comorbidity (p < 0.001). The
      mean EQ-5D VAS scores for patients in GOLD stages 2, 3, and 4 were 68 (SD, 16),
      62 (SD, 17), and 58 (SD, 16), respectively. The mean utility scores were 0.79
      (SD, 0.20) for patients in GOLD stage 2, 0.75 (SD, 0.21) for patients in GOLD
      stage 3, and 0.65 (SD, 0.23) for patients in GOLD stage 4. Effect sizes for the
      difference in utility scores between patients in GOLD stages 3 and 4 were more
      than twice as high as those for the difference between patients in GOLD stages 2
      and 3. Gender, postbronchodilator FEV(1) percent predicted, the number of
      hospital admissions and emergency department visits in the year prior to baseline
      measurements, measures of comorbidity, and BMI were independently associated with
      EQ-5D utility. EQ-5D utility scores also differed between patients from different
      countries. French patients especially had lower utility scores than US patients.
      Utility scores calculated with the US value set were on average 5% higher than
      those calculated with the UK value set. CONCLUSIONS: Increasing severity of COPD
      was associated with a significant decline in EQ-5D VAS scores and utility scores.
      These results demonstrate that a generic instrument can assess COPD impact on
      quality of life and that the scores discriminate between patient groups of known
      severity. These utility scores will be useful in cost-effectiveness assessments.

PMID- 17035448
TI  - Chylothorax complicating repairs of the descending and thoracoabdominal aorta.
AB  - BACKGROUND: Chylothorax occurring during thoracic aortic surgery is an infrequent
      but serious complication. The purpose of this study was to analyze our experience
      with this complication and the resulting outcomes. METHODS: From January 1991 to
      July 2005, we performed 1,233 descending thoracic and thoracoabdominal aortic
      surgical procedures. A retrospective review was performed to analyze and identify
      preoperative and operative risk factors as well as management outcomes of
      postoperative chylothorax (PCT). RESULTS: PCT developed in five patients (0.4%).
      All five cases occurred with descending thoracic aortic aneurysm repair, and 80%
      (four of five patients) were undergoing aortic reoperation. All patients were
      managed successfully with no mortality. Risk factors for the development of
      chylothorax were descending thoracic aortic repair (p = 0.006) and thoracic
      aortic reoperations (p = 0.0003). Nonoperative management was successful in 60%
      (three of five patients). Two patients required left thoracotomy with direct
      ligation. Mean hospital length of stay was 35 days (range, 15 to 60 days). Mean
      follow-up was 33 months (range, 3 to 69 months) with no recurrence of chylothorax
      or additional morbidity or mortality. CONCLUSIONS: Chylothorax is more likely to
      occur with reoperations and repairs involving the descending thoracic aorta.
      Although PCT is associated with longer hospital length of stay, it is not
      associated with increased infectious complications. Early identification and
      prompt treatment may decrease both early and late morbidity and mortality.

PMID- 17035447
TI  - Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30
      year pulmonary function and 40-year mortality: a follow-up in middle-aged rural
      men.
AB  - PURPOSE: To describe the 30-year cumulative incidence of chronic bronchitis and
      COPD in relation to smoking habits. The effect of chronic bronchitis on pulmonary
      function and mortality was also examined. METHODS: Middle-aged men belonging to
      two rural Finnish cohorts of the Seven Countries Study (n = 1,711 in 1959) were
      followed up for up to 40 years until 2000. Standard questionnaires were used to
      measure chronic bronchitis, and repeated spirometry was used to evaluate
      pulmonary function during the 30 years. Forty-year mortality data were examined.
      RESULTS: The cumulative incidence of chronic bronchitis and COPD was 42% and 32%,
      respectively, in continuous smokers, compared to 26% and 14% in ex-smokers and
      22% and 12% in never-smokers. During the follow-up, subjects with chronic
      bronchitis had on average 252 mL (95% confidence interval, 211 to 293 mL) lower
      forced expiratory volume than those without it. The decrease in forced expiratory
      volume attributable to chronic bronchitis was most pronounced in those with
      persistent symptoms and in smokers. In subjects with chronic bronchitis, all
      cause mortality was increased by a hazard ratio of 1.30 (95% confidence interval,
      1.02 to 1.65). Smokers with chronic bronchitis who decreased their daily
      cigarette consumption increased their median life span by 2.4 years. CONCLUSIONS:
      The lifetime risk of chronic bronchitis among smokers is approximately two in
      five, and almost one half of smokers who have chronic bronchitis also acquire
      COPD. Chronic bronchitis is related to earlier death, also in never-smokers,
      probably partly through a rapid decline in pulmonary function.

PMID- 17035449
TI  - Nontraumatic disruption of the fibrocartilaginous trachea: causes and clinical
      outcomes.
AB  - BACKGROUND: Nontraumatic disruption of the fibrocartilaginous trachea is rare,
      and the appropriate management of this condition is not well-characterized.
      METHODS: Retrospective analysis of the clinical features, causes, and outcomes
      with surgical and nonsurgical management in nine adult patients with nontraumatic
      fibrocartilaginous tracheal disruption identified by bronchoscopy from January 1,
      1975, to December 31, 2004, at a single institution. RESULTS: The most common
      cause was external beam radiotherapy (RT) in five patients. Other causes included
      postoperative complications of cervical and superior mediastinal operations in
      three patients and Aspergillus fumigatus-induced ulcerative tracheobronchitis in
      one patient post-lung transplantation. Four patients were treated surgically;
      three because of significant pneumomediastinum and one because the size of the
      tracheal defect made spontaneous healing seem unlikely. A silicone stent was
      placed in one patient for concomitant tracheal narrowing, and one patient was
      treated medically with antifungal agents. The remaining three patients were
      followed up serially without any intervention. With these treatments, only one
      patient died as a consequence of tracheal disruption. Repeat bronchoscopies were
      performed in seven of the remaining eight patients and confirmed healing of the
      necrotic defect in all. CONCLUSION: Nontraumatic disruption of the
      fibrocartilaginous trachea occurs most commonly as a consequence of external beam
      RT. It can also occur as a complication of cervical and superior mediastinal
      operations or from A fumigatus-induced ulcerative tracheobronchitis post-lung
      transplantation. Although surgical treatment has been generally recommended for
      patients with this condition, patients with contained disruptions without
      evidence of pneumomediastinum may be managed nonoperatively.

PMID- 17035450
TI  - Air leaks after lobectomy increase the risk of empyema but not of cardiopulmonary
      complications: a case-matched analysis.
AB  - PURPOSE: To assess whether the presence and duration of air leaks after lobectomy
      are associated with an increased incidence of cardiopulmonary complications.
      METHODS: Propensity score analysis was used on 726 patients undergoing pulmonary
      lobectomy from 1995 through 2004 to form three well-matched pairs of patients:
      patients with prolonged air leak (PAL) [> 7 days] and without air leak; patients
      with short air leak (SAL) [< or = 7 days] and without air leak; and patients with
      SAL and PAL. These matched groups were then compared to assess postoperative
      hospital stay and early outcome. RESULTS: Patients with SAL had a longer
      postoperative hospital stay compared to patients without air leak (8.6 days vs
      7.8 days, respectively; p < 0.0001) but had similar morbidity and mortality.
      Patients with PAL had a longer postoperative hospital stay compared to patients
      without air leak (16.2 days vs 8.3 days, respectively; p < 0.0001) and with SAL
      (16.9 days vs 9 days, respectively; p < 0.0001), but similar cardiopulmonary
      complications were noted between the groups. Patients with PAL had a higher rate
      of empyema compared to patients without air leak and with SAL (8.2% vs 0%, p =
      0.01 and 10.4% vs.1.1%, p = 0.01, respectively). CONCLUSIONS: The presence of air
      leak was not associated with an increased incidence of cardiopulmonary morbidity
      but was associated with an increased risk of empyema. Future prospective studies
      are needed to confirm safety of fast track in patients with air leak.

PMID- 17035451
TI  - Repeated sputum inductions induce a transient neutrophilic and eosinophilic
      response.
AB  - INTRODUCTION: Sputum induction is a tool to monitor airway inflammation, yet it
      may induce by itself a neutrophilic response when repeated within 24 to 48 h.
      This limits its repeated use in clinical trials. OBJECTIVE: We aimed to
      investigate the induction and resolution of inflammation generated by repeated
      sputum inductions. SUBJECTS AND DESIGN: Sixteen healthy intermittent smokers
      participated in a study on the short-term effects of smoking. The nonsmoking arm
      consisted of seven successive sputum inductions with increasing time intervals
      (3, 6, 12, 24, 48, and 96 h). Inflammatory cellular characteristics and different
      soluble mediators were investigated. MEASUREMENTS AND RESULTS: The median
      percentage of sputum neutrophils increased significantly from baseline to 6 h
      (58.9% [range, 31.8 to 94.2%] to 83.2% [range, 26.7 to 98.3%], respectively).
      Surprisingly, the percentage of eosinophils also increased significantly from
      baseline to 6, 12, 24, and 48 h, as follows: 0.3% (range, 0.0 to 1.2%) to 1.7%
      (range, 0.0 to 15.5%), 2.2% (range, 0.5 to 12.5%), 1.2% (range, 0.0 to 4.8%), and
      0.8% (range, 0.0 to 2.8%), respectively. Interleukin-8 increased significantly
      from baseline to 24 h (1,553 pg/mL [range, 462 to 8,192 pg/mL] to 2,178 pg/mL
      [range, 666 to 128,544 pg/mL]). CONCLUSIONS: Repeated sputum inductions should
      preferably be avoided within 48 h. It induces not only a short-lived neutrophilic
      response but also a prolonged eosinophilic inflammatory response in healthy
      subjects, possibly by local changes in osmolarity, and subsequent epithelial
      and/or mast cell activation.

PMID- 17035452
TI  - Long-term symptom recovery and health-related quality of life in patients with
      mild-to-moderate-severe community-acquired pneumonia.
AB  - STUDY OBJECTIVES: The long-term outcomes of patients with community-acquired
      pneumonia (CAP) in terms of symptom resolution and health-related quality of life
      (HRQL) is unknown. Our objective was to determine the rate of symptom resolution
      using validated patient-based outcome measures, and to assess HRQL 18 months
      after the episode. PARTICIPANTS: Patients were recruited from a group enrolled in
      a randomized trial comparing two durations of treatment for CAP. Between 2000 and
      2003, we included 102 adults with a mild-to-moderate-severe CAP (pneumonia
      severity index, < or = 110). INTERVENTIONS: CAP-related symptoms were assessed
      until month 18 using the CAP score. The CAP score was divided into respiratory
      and well-being sections to assess the recovery of respiratory and well-being
      symptoms separately. The HRQL was assessed at 18 months using the Medical
      Outcomes Study 36-item short form (SF-36) questionnaire and compared to a Dutch
      reference group. RESULTS: Respiratory symptoms resolved within 14 days, while the
      well-being symptoms resolved more slowly. Taking the prepneumonia status into
      account, patients recovered fully from pneumonia after 6 months. Patients with
      comorbid conditions had significantly more symptoms prepneumonia and during
      follow-up than patients without comorbidities, but at all time points the
      proportion of patients that reached > or = 80% of the prepneumonia health level
      did not depend on comorbidity, age, or etiology. SF-36 scores at 18 months were
      significantly impaired in four of the eight dimensions for patients with comorbid
      illness, but did not differ from the reference population for patients without
      comorbid illness. CONCLUSION: Patients with mild-to-moderate-severe CAP recover
      fully from pneumonia after 6 months. The presence of symptoms beyond 28 days and
      any impairment in HRQL were found to reflect age and comorbidity rather than the
      persistent effects of the pneumonia itself.

PMID- 17035453
TI  - Pathophysiology of pneumothorax following ultrasound-guided thoracentesis.
AB  - STUDY OBJECTIVES: Pneumothorax following ultrasound-guided thoracentesis is rare.
      Our goal was to explain the mechanisms of pneumothorax following ultrasound
      guided thoracentesis in a setting where pleural manometry is routinely used.
      METHODS: We reviewed the patient records and procedure reports of 401 patients
      who underwent ultrasound-guided thoracentesis. When manometry was performed,
      pleural space elastance was determined. A model assuming dependence of the
      pleural space elastic properties on respiratory system elastic properties was
      used to isolate cases with presumed normal pleural space elastance. Elastance
      outside mean +/- SD x 2 of the isolated sample was considered abnormal. Four
      radiographic criteria of unexpandable lung were used: visceral pleural peel,
      lobar atelectasis, basilar pneumothorax, and pneumothorax with ipsilateral shift.
      RESULTS: There were 102 diagnostic thoracenteses, 192 therapeutic thoracenteses
      with pleural manometry, and 73 therapeutic thoracenteses without manometry. There
      was one pneumothorax that occurred from lung puncture and eight unintentional
      pneumothoraces, all of which showed radiographic evidence of unexpandable lung.
      Four of eight unintentional pneumothoraces had abnormal elastance; none had
      excessively negative pleural pressure (< -25 cm H(2)O). CONCLUSIONS:
      Unintentional pneumothoraces cannot be prevented by monitoring for symptoms or
      excessively negative pressure. These pneumothoraces were drainage related rather
      than due to penetrating lung trauma or external air introduction. We speculate
      that unintentional pneumothoraces are caused by transient, parenchymal-pleural
      fistulae caused by nonuniform stress distribution over the visceral pleura that
      develop during large-volume drainage if the lung cannot conform to the shape of
      the thoracic cavity in some patients with unexpandable lung. These fistulae
      appear to be pressure dependent, and the resulting pneumothoraces rarely require
      treatment. Drainage-related pneumothorax is an unavoidable complication of
      ultrasound-guided thoracentesis and appears to account for the vast majority of
      pneumothoraces occurring in a procedure service.

PMID- 17035454
TI  - The safety of bronchoscopy in a pulmonary fellowship program.
AB  - STUDY OBJECTIVE: To determine the complication rate from supervised training
      bronchoscopy in a single pulmonary fellowship program, and to examine the effects
      of fellow and faculty experience on this complication rate. DESIGN: A
      retrospective review of preexisting quality improvement data from one center for
      the time period July 1, 1991, until June 30, 2005, was performed. The data were
      stratified based on the fellow year group and the staff experience level. The
      types of complications were recorded. SETTING: The study was performed at an
      accredited pulmonary and critical care fellowship program at a military medical
      center in the United States. PARTICIPANTS: Fifty-one pulmonary and critical care
      medicine fellows and 20 staff supervising physicians performed the bronchoscopies
      that were included in this study. RESULTS: A total of 3,538 training
      bronchoscopies were performed during the study period with 73 complications for a
      complication rate of 2.06%. The most common complication was pneumothorax. The
      overall complication rates for first-year fellows (1stYFs), second-year fellows,
      and third-year fellows were not significantly different from the total
      complication rate. Training bronchoscopies supervised by junior staff had a
      complication rate not significantly different from that of senior staff. The
      cumulative complication rate for the first trimester for 1stYFs was 3.1%, whereas
      the cumulative complication rate for the second plus the third trimester for
      1stYFs was 1.57% (p < 0.05). CONCLUSIONS: Training bronchoscopy performed during
      a pulmonary fellowship is a safe procedure in a supervised setting. Patients
      undergoing bronchoscopy performed by novice bronchoscopists have an increased
      complication rate during the first trimester of bronchoscopist training.

PMID- 17035455
TI  - Differentiating peripheral pulmonary lesions based on images of endobronchial
      ultrasonography.
AB  - PURPOSE: To attempt to develop a simple method to discriminate between neoplasm
      and nonneoplasm peripheral pulmonary lesions based on images of endobronchial
      ultrasonography (EBUS). METHODS: Between June 2004 and June 2005, 151 patients
      with bronchoscopic peripheral lesions that could not be detected via a
      conventional bronchoscope underwent EBUS for advanced localization with a 20-MHz
      miniature radial probe in a tertiary-referral teaching hospital. The image
      characteristics were applied subsequently to correlate definite histopathologic
      results in studied patients. RESULTS: Based on an initial 20 consecutive patients
      with a definite diagnosis, four image characteristics were issued: (1) continuous
      hyperechoic margin outside the lesion, (2) homogeneous, or heterogeneous internal
      echoes, (3) hyperechoic dots in the lesion, and (4) concentric circles along the
      echo probe. In the following 131 patients, excluding five cases due to
      inconsistent typing, 93 patients (73.8%) established a diagnosis later. Most
      cases involving the image characteristics of homogenous internal echoes and
      concentric circles had nonneoplasm lesions (18 of 19 cases, 94.7%, and 14 of 16
      cases, 87.5%, respectively). The difference shown in these two respects with
      neoplasm lesions was significant by univariate analysis (p < 0.001), although
      only concentric circles had a significant p value after multivariate analysis.
      Another two image patterns (continuous hyperechoic margins and hyperechoic dots)
      did not yield a significant difference (p = 0.090 and p = 0.079, respectively).
      The average additional time for EBUS was 3.94 min (1.5 to 10 min). CONCLUSION:
      EBUS can provide characteristic information to differentiate the nature of a
      peripheral pulmonary lesion from the image characteristics of concentric circles.

PMID- 17035456
TI  - The current treatment of pulmonary arterial hypertension: time to redefine
      success.
AB  - In the past decade, three classes of medications have been approved for the
      treatment of pulmonary arterial hypertension. A review of the clinical trial data
      for the prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors
      has shown that all agents have similar efficacy on the 6-min walk distance over
      12 to 16 weeks, which was the primary end point in the randomized clinical
      trials. However, little is known about their long-term efficacy or about how
      these drugs affect the underlying disease, if at all. Successful therapy is
      currently defined as an improvement in exercise tolerance over a 4-month period.
      Future trials need to better characterize how therapies affect the pulmonary
      vasculature pathologically, biologically, and hemodynamically, and whether
      survival is actually improved.

PMID- 17035457
TI  - How viral infections cause exacerbation of airway diseases.
AB  - Exacerbations of asthma and COPD are major causes of morbidity, mortality, and
      health-care costs. Over the last decade, studies using new molecular diagnostic
      techniques have established that respiratory viruses are a major cause of
      exacerbations of both asthma and COPD. The most prevalent viruses detected during
      exacerbations are the rhinoviruses. Despite the burden of disease associated with
      exacerbations, little is known about the mechanisms of virus-induced
      exacerbations of airway diseases. Exacerbations are associated with increased
      airway inflammation in patients with both asthma and COPD, but many questions
      remain unanswered regarding the key inflammatory cells and mediators involved.
      Identifying the key inflammatory mediators involved in exacerbations holds the
      promise of developing diagnostic and prognostic markers of exacerbation. In
      addition, such studies can identify new therapeutic targets for the development
      of novel drugs for the prevention and treatment of exacerbations.

PMID- 17035458
TI  - Advances in chemotherapy of non-small cell lung cancer.
AB  - In the United States, lung cancer kills more men and woman than the next three
      most common cancers combined. Unfortunately, the long-term outcome of lung cancer
      is still dismal with a 5-year survival rate of 15%. However, significant
      improvements in median survival times and 1-year and 2-year survival rates have
      been achieved in the last decade. This progress has been accomplished not only
      because of better surgical techniques but also because of the use of platinum
      based regimens with newer chemotherapy agents and, more recently, targeted
      therapy. The role of chemotherapy as an integral part of the treatment of lung
      cancer has expanded significantly, particularly in the last few years with the
      proven benefit of adjuvant chemotherapy. For advanced stage non-small cell lung
      cancer (NSCLC), chemotherapy prolongs survival and improves quality of life in
      patients with good performance status, and appears to provide symptomatic
      improvement in patients with decreased performance status. Platinum-based doublet
      chemotherapy regimens are now the standard of care in patients with advanced
      stage NSCLC, and non-platinum-based combination therapies are reasonable
      alternatives in certain populations. The combination of the vascular endothelial
      growth factor inhibitor bevacizumab and chemotherapy has proven to prolong
      survival. As agents such as monoclonal antibodies, small molecules inhibitors of
      tyrosine kinase, and direct inhibitors of proteins involved in lung cancer
      proliferation are being developed and tested, we are optimistic that these agents
      will result in improvement in the survival and quality of life of lung cancer
      patients.

PMID- 17035459
TI  - Diagnostic usefulness of B-type natriuretic peptide and functional consequences
      of muscle alterations in COPD and chronic heart failure.
AB  - COPD affects up to one third of patients with chronic heart failure. The
      coexistence of COPD and chronic heart failure presents clinicians with diagnostic
      and therapeutic challenges. Measurement of B-type natriuretic peptide plasma
      levels facilitates the diagnosis of acute dyspnea in patients known to have both
      COPD and chronic heart failure. Patients with COPD or chronic heart failure have
      skeletal muscle abnormalities that limit functional capacity independently from
      primary organ failure. Exercise training reverses skeletal muscle abnormalities
      in patients with COPD or chronic heart failure and may be particularly indicated
      in patients with coexistent COPD and chronic heart failure.

PMID- 17035460
TI  - Smoking cessation counseling: a practice management perspective.
AB  - Individuals continue to smoke despite its numerous proven adverse health effects.
      Now viewed as a chronic medical condition, health-care professionals are more
      involved in cessation efforts. Physicians are often the first line of defense,
      providing intervention through prescription management and counseling. Some
      insurers recognize these efforts as health promoting and cost saving, revising
      policies to include reimbursement. This article addresses the most recent smoking
      cessation policy revision implemented by the Centers for Medicare and Medicaid
      Services.

PMID- 17035461
TI  - The expanding spectrum of Mycobacterium avium complex-associated pulmonary
      disease.
AB  - Nontuberculous mycobacteria (NTM) are increasingly recognized as important
      pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most
      lung infections due to NTM. Patients with preexisting lung disease or
      immunodeficiency are at greatest risk for developing MAC infection. The majority
      of MAC pulmonary cases, however, occur in immunocompetent elderly women in
      association with nodular infiltrates and bronchiectasis. More recently, pulmonary
      disease has also been described in immunocompetent patients after exposure to MAC
      contaminated hot tubs. We describe a case of aggressive MAC lung disease in a
      young immunocompetent female patient without preexisting lung disease whose
      clinical and pathologic characteristics do not fit into any of these categories
      and may represent a unique manifestation of MAC lung disease.

PMID- 17035462
TI  - A 37-year-old woman with multiple pulmonary nodular opacities and hemoptysis.

PMID- 17035463
TI  - Recurrent dyspnea on exertion in a 71-year-old man with prior pulmonary embolism.

PMID- 17035464
TI  - A 48-year-old woman with multiple pulmonary nodules and a right ventricular mass.

PMID- 17035466
TI  - Documenting research in scientific articles: guidelines for authors: reporting
      research designs and activities.

PMID- 17035465
TI  - A review of pediatric nonrespiratory sleep disorders.
AB  - Sleep problems are extremely common during childhood, from infancy to
      adolescence. Despite the prevalence of sleep problems, childhood sleep disorders
      are often underrecognized and undiagnosed, despite being either preventable or
      treatable. Sleep impacts almost all aspects of a child's functioning, and thus
      the increased recognition and treatment of sleep disorders will positively affect
      a child's well-being. Children experience the same broad range of sleep
      disturbances encountered in adults, including sleep apnea, insomnia, parasomnia,
      delayed sleep phase, narcolepsy, and restless legs, but their clinical
      presentation, evaluation, and management may differ. Although snoring and sleep
      apnea may be the most common indication for an overnight sleep study in a child,
      one quarter of children presenting to a sleep clinic for evaluation will have a
      second sleep diagnosis, which is often nonrespiratory in nature. Especially in
      children, ruling out sleep apnea is rarely the end point of the sleep evaluation.
      Clinicians involved in sleep medicine must be prepared to recognize, evaluate,
      and manage plans for sleep disorders across the lifespan of the patient. This
      article will provide an updated review of nonrespiratory pediatric sleep
      disorders within a developmental framework.

PMID- 17035467
TI  - A 70-year-old man with migratory pulmonary infiltrates.

PMID- 17035468
TI  - Is the more (intricate) the better?

PMID- 17035469
TI  - d-ROMs test detects ceruloplasmin, not oxidative stress.

PMID- 17035470
TI  - Is endobronchial ultrasound necessary for transbronchial lung biopsy in solitary
      pulmonary nodule?

PMID- 17035471
TI  - Is intensive insulin therapy safe in the critically ill?

PMID- 17035472
TI  - Evaluation of the causes of racial disparity in surgical treatment of early-stage
      lung cancer.

PMID- 17035473
TI  - Left ventricular diastolic abnormalities in obese subjects.

PMID- 17035474
TI  - Severe sepsis due to melioidosis.

PMID- 17035475
TI  - Attention to doping controls required when prescribing for athletes.

PMID- 17035476
TI  - Respiratory research output.

PMID- 17035477
TI  - Complete response following preoperative chemotherapy for resectable non-small
      cell lung cancer.

PMID- 17035478
TI  - Is bronchoscopy dangerous in the pretreatment workup of non-small cell lung
      cancer patients?

PMID- 17035479
TI  - Eccentric overload training in patients with chronic Achilles tendinopathy: a
      systematic review.
AB  - BACKGROUND: Eccentric overload training seems to be a promising conservative
      intervention in patients with chronic Achilles tendinopathy. The efficacy of
      eccentric overload training on the outcome measures of pain and physical
      functioning are not exactly clear. STUDY DESIGN: Systematic review of the
      literature. METHODS: Electronic databases were searched for randomised clinical
      trials concerning eccentric overload training in patients with chronic Achilles
      tendinopathy. The Delphi list was used to assess the methodological quality of
      the studies. RESULTS: Nine clinical trials were included. Only one study had
      sufficient methodological quality. The included trials showed an improvement in
      pain after eccentric overload training. Because of the methodological
      shortcomings of the trials, no definite conclusion can be drawn concerning the
      effects of eccentric overload training in patients with chronic Achilles
      tendinopathy. CONCLUSION: The effects of eccentric exercise training in patients
      with chronic Achilles tendinopathy on pain are promising; however, the magnitude
      of the effects cannot be determined. Large, methodologically sound studies from
      multiple sites in which functional outcome measures are included are warranted.

PMID- 17035480
TI  - Notice of redundant publication. Tendon and paratendon Achilles microcirculation
      in eccentric training and an Achilles wrap in insertional and mid-portion
      tendinopathy--a randomized trial.

PMID- 17035482
TI  - TCDD-induced alterations in gene expression profiles of the developing mouse paw
      do not influence morphological differentiation of this potential target tissue.
AB  - The aryl-hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that mediates the toxicity of certain halogenated aromatic hydrocarbons including
      2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD). These compounds are potent
      developmental toxicants that can alter gene expression and disrupt processes of
      proliferation and differentiation. It has not yet been determined which tissues
      during development are most sensitive to these compounds, nor which genes are
      directly associated with the toxicities. We developed a transgenic (TG) mouse
      model to delineate the temporal and spatial context of transcriptionally active
      AhR by utilizing a dioxin responsive element-linked LacZ reporter system. The
      present study focuses on the pattern of TCDD-induced transgene expression
      localized to the footpad and digits of the paws between gestational days (GD) 13
      and 18. Paw morphology was evaluated at several developmental stages following
      TCDD exposure. Gene expression profiles acquired by microarray technology were
      evaluated in the paws of fetuses exposed at GD 14.5. The results showed that TCDD
      exposure in utero induced LacZ expression in the developing paws. This expression
      appeared to be localized to the mesenchymal cell layer. Gross morphological
      changes were not observed in the paws prior to or after birth following TCDD
      exposure in utero. However, significant alterations in gene expression profiles
      in the developing paws were observed at 24 h following TCDD exposure in utero.
      These results indicate that the developing paw is a target tissue of TCDD in
      terms of altered gene expression, further validating the use of this AhR
      responsive reporter gene TG mouse model in studying AhR ligand-mediated
      responsiveness. However, the linkage of these changes to detectable biological
      outcomes in the paw remains unclear.

PMID- 17035481
TI  - Effects of rugby sevens matches on human neutrophil-related non-specific
      immunity.
AB  - AIMS: To evaluate the influences of the accumulative effect of two consecutive
      rugby sevens matches (Sevens) on aspects of human neutrophil-related non-specific
      immunity. METHODS: In seven players participating in the Japan Sevens, neutrophil
      reactive oxygen species (ROS) production capability and phagocytic activity were
      measured using flow cytometry, and serum opsonic activity (SOA) was assessed by
      measuring neutrophil ROS using the peak height of lucigenin-dependent
      chemiluminescence before and after two consecutive matches. RESULTS: ROS showed
      no change immediately after the first match, and had significantly (P<0.05)
      increased 4 h later, but showed a decrease after the second match. Phagocytic
      activity showed no change immediately after the first match, but had
      significantly (P<0.01) decreased 4 h later, and showed a further decrease after
      the second match, although it was not significant. SOA significantly (P<0.01)
      increased after the first match, and still maintained its high 4 h later, but
      decreased after the second match. ROS production capability, phagocytic activity
      and SOA significantly (P<0.01) decreased after the second match. CONCLUSIONS:
      When rugby players play two consecutive Sevens matches, the exercise loading is
      thought to be hard, similar to that experienced during a marathon race and
      intensive or long training in a training camp, although the expected changes were
      not seen after the first match. Differences between after the first and the
      second matches may be due to the "cumulative effect".

PMID- 17035483
TI  - A photogrammetric technique for the analysis of palatal three-dimensional changes
      during rapid maxillary expansion.
AB  - The aim of this study was to assess, by a digital photogrammetric technique, the
      relative dimensional changes before and after rapid maxillary expansion (RME).
      The transverse diameters and volumetric variations of the palate were measured by
      photogrammetry on study casts taken at three different phases of therapy: at the
      beginning of treatment (T1), on removal of the rapid expander, after expansion
      and retention for three months (T2), and six months after appliance removal (T3).
      The sample consisted of 30 children, (age range 7-8 years), all with a crossbite;
      15 were angle Class I, six Class II and nine Class III. They were treated with an
      acrylic splint expander with two turns per day until the maxillary molar palatal
      cusps were in contact with the mandibular molar buccal cusps. The RME device was
      used as a passive retainer for three months, after which it was removed. During
      the following six months, no retention was used and no orthodontic treatment was
      undertaken. The findings demonstrated a significant relapse (P < 0.001) in the
      dental transverse diameter in all patients six months after appliance removal,
      although the palatal volume remained stable.

PMID- 17035484
TI  - How do we evaluate the economics of health care?
AB  - Economic evaluation has become an integral component of health service research
      in recent years and will no doubt become more influential. As resources are
      reduced in health services, more questions are likely to be asked on the costs
      and benefits of new treatments. Questions are also likely to be aimed at
      treatments that are currently provided. Economics related to health care is
      complex and numerous methods of economic evaluation exist. Full economic
      evaluation involves the assessment of both costs and outcomes and is ideal for
      comparing the efficiency of treatments. Partial evaluations can also provide
      useful information on the contribution of component costs to treatment costs as a
      whole. The aim of this review is to assess the various methods available to
      evaluate the economics of health care and to place in context how these methods
      may be used within dentistry.

PMID- 17035485
TI  - In vitro toxicity evaluation of silver soldering, electrical resistance, and
      laser welding of orthodontic wires.
AB  - The long-term effects of orthodontic appliances in the oral environment and the
      subsequent leaching of metals are relatively unknown. A method for determining
      the effects of various types of soldering and welding, both of which in turn
      could lead to leaching of metal ions, on the growth of osteoblasts, fibroblasts,
      and oral keratinocytes in vitro, is proposed. The effects of cell behaviour of
      metal wires on osteoblast differentiation, expressed by alkaline phosphatase
      (ALP) activity; on fibroblast proliferation, assayed by the 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenil)-2H
      tetrazolium-phenazine ethosulphate method; and on keratinocyte viability and
      migration on the wires, observed by scanning electron microscopy (SEM), were
      tested. Two types of commercially available wires normally used for orthodontic
      appliances, with a similar chemical composition (iron, carbon, silicon, chromium,
      molybdenum, phosphorus, sulphur, vanadium, and nitrogen) but differing in nickel
      and manganese content, were examined, as well as the joints obtained by
      electrical resistance welding, traditional soldering, and laser welding. Nickel
      and chromium, known as possible toxic metals, were also examined using pure
      nickel- and chromium-plated titanium wires. Segments of each wire, cut into
      different lengths, were added to each well in which the cells were grown to
      confluence. The high nickel and chromium content of orthodontic wires damaged
      both osteoblasts and fibroblasts, but did not affect keratinocytes. Chromium
      strongly affected fibroblast growth. The joint produced by electrical resistance
      welding was well tolerated by both osteoblasts and fibroblasts, whereas
      traditional soldering caused a significant (P < 0.05) decrease in both osteoblast
      ALP activity and fibroblast viability, and prevented the growth of keratinocytes
      in vitro. Laser welding was the only joining process well tolerated by all tested
      cells.

PMID- 17035486
TI  - Significance of low positive scores obtained with a method other than
      acceleration in the BDProbeTec-Strand displacement amplification test for
      detection of Neisseria gonorrhoeae.

PMID- 17035487
TI  - Direct detection of Mycobacterium tuberculosis complex DNA and rifampin
      resistance in clinical specimens from tuberculosis patients by line probe assay.
AB  - The INNO-LiPA.Rif TB test (LiPA) has only been applied to a limited number of
      clinical specimens. To assess the utility of this test for detecting
      Mycobacterium tuberculosis complex DNA and rifampin (RMP) resistance, 420 sputum
      samples comprising specimens from untreated (n=160) and previously treated
      (n=260) patients from 11 countries in Asia, Africa, Europe, and Latin America
      were tested. DNA was extracted from sputum samples by using a modification of the
      Boom's method, while the rpoB core region was amplified by nested PCR. The
      results were analyzed in conjunction with those obtained by Ziehl-Neelsen (ZN)
      microscopy and by culture on solid media. The LiPA test was positive for M.
      tuberculosis complex DNA in 389 (92.9%) specimens, including 92.0% (286 of 311)
      ZN-positive and 94.5% (103 of 109) ZN-negative specimens. Of these, 30.6% were
      RMP resistant. In contrast, 74.3% of the specimens were positive for M.
      tuberculosis by culture, and 30.8% of them were RMP resistant. LiPA detected M.
      tuberculosis complex DNA in 92.4% (110 of 119) of the culture-positive and 100.0%
      (41 of 41) of the culture-negative specimens from untreated patients. There was a
      99.6% concordance between the RMP resistance as determined by culture and by the
      LiPA test. With an optimal DNA extraction method, LiPA allows rapid detection of
      M. tuberculosis complex DNA and RMP resistance directly from sputum specimens.
      LiPA can still provide useful information when culture fails for various reasons.
      The rapid availability of this information is necessary to adjust patient
      treatment and avoid the risk of amplification of drug resistance.

PMID- 17035488
TI  - Use of smear-positive samples to assess the PCR-based genotype MTBDR assay for
      rapid, direct detection of the Mycobacterium tuberculosis complex as well as its
      resistance to isoniazid and rifampin.
AB  - Isoniazid (INH) and rifampin (RIF) are two of the most important antituberculosis
      drugs, and resistance to both of these drugs can often result in treatment
      failure and fatal clinical outcome. Resistance to these two first-line drugs is
      most often attributed to mutations in the katG, inhA, and rpoB genes.
      Historically, the identification and testing of the susceptibility of
      Mycobacterium tuberculosis complex (MTBC) strains takes weeks to complete. Rapid
      detection of resistance using the PCR-based Genotype MTBDR assay (Hain
      Lifescience GmbH, Nehren, Germany) has the potential to significantly shorten the
      turnaround time from specimen receipt to reporting of results of susceptibility
      testing. Therefore, the aim of the present study was to determine (i) the
      sensitivity and accuracy of the Genotype MTBDR assay for the detection of MTBC
      strains and (ii) the ability of the assay to detect the presence of INH and RIF
      resistance-associated mutations in katG and rpoB from samples taken directly from
      smear-positive clinical specimens. The results were compared with those obtained
      with the reference BACTEC 460TB system combined with standard DNA sequencing
      analysis methods for katG, inhA, and rpoB. A total of 92 drug-resistant and 51
      pansusceptible smear-positive specimens were included in the study. The Genotype
      MTBDR assay accurately and rapidly detected MTBC strains in 94.4% of the 143
      specimens and showed a sensitivity of 94.4% for katG and 90.9% for rpoB when used
      directly on smear-positive specimens. The assay correctly identified INH
      resistance in 48 (84.2%) of the 57 specimens containing strains with resistance
      to high levels of INH (0.4 microg/ml) and RIF resistance in 25 (96.2%) of the 26
      specimens containing RIF-resistant strains.

PMID- 17035489
TI  - Borrelia burgdorferi genetic markers and disseminated disease in patients with
      early Lyme disease.
AB  - Three genetic markers of Borrelia burgdorferi have been associated with
      disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type
      (RST), and vlsE. Here, we modified previous methods so as to identify the three
      markers by PCR and restriction fragment length polymorphism in parallel, analyzed
      B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients,
      and correlated the results with evidence of dissemination. OspC type A was found
      approximately twice as frequently in patients with disseminated disease, whereas
      type K was identified approximately twice as often in those without evidence of
      dissemination, but these trends were not statistically significant. The remaining
      seven types identified were found nearly equally in patients with or without
      evidence of dissemination. RST 1 strains were significantly associated with
      dissemination (P=0.03), whereas RST 2 and RST 3 strains tended to have an inverse
      association with this outcome. The vlsE gene was identified in all 91 cases,
      using primer sets specific for an N-terminal sequence of B. burgdorferi strain
      B31 (vlsEB31) or strain 297 (vlsE297), but neither marker was associated with
      dissemination. Specific combinations of the three genetic markers usually
      occurred together. OspC type A was always found with RST 1 and vlsEB31, type K
      was always identified with RST 2 and more often with vlsE297, and types E and I
      were almost always found with RST 3 and equally often with vlsEB31 and vlsE297.
      We conclude that B. burgdorferi strains vary in their capacity to disseminate,
      but almost all strains isolated from EM lesions sometimes caused disseminated
      disease.

PMID- 17035490
TI  - Characterization of a Brucella sp. strain as a marine-mammal type despite
      isolation from a patient with spinal osteomyelitis in New Zealand.
AB  - Naturally acquired infection of humans with a marine mammal-associated Brucella
      sp. has only been reported once previously in a study describing infections of
      two patients from Peru. We report the isolation and characterization of a strain
      of Brucella from a New Zealand patient that appears most closely related to
      strains previously identified from marine mammals. The isolate was preliminarily
      identified as Brucella suis using conventional bacteriological tests in our
      laboratory. However, the results profile was not an exact match, and the isolate
      was forwarded to four international reference laboratories for further
      identification. The reference laboratories identified the isolate as either B.
      suis or B. melitensis by traditional bacteriological methods in three
      laboratories and by a molecular test in the fourth laboratory. Molecular
      characterization by PCR, PCR-restriction fragment length polymorphism, and DNA
      sequencing of the bp26 gene; IS711; the omp genes omp25, omp31, omp2a, and omp2b;
      IRS-PCR fragments I, III, and IV; and five housekeeping gene fragments was
      conducted to resolve the discrepant identification of the isolate. The isolate
      was identified to be closely related to a Brucella sp. originating from a United
      States bottlenose dolphin (Tursiops truncatus) and common seals (Phoca vitulina).

PMID- 17035491
TI  - Genotyping of clinical herpes simplex virus type 1 isolates by use of restriction
      enzymes.
AB  - Recently, three distinct genotypes of clinical herpes simplex virus type 1 (HSV
      1) isolates were identified based on DNA sequence information and phylogenetic
      analysis of clinical isolates and laboratory strains. We utilized single
      nucleotide polymorphism within the genes coding for glycoproteins G and I for
      rapid genotype classification by PCR and restriction enzyme cleavage. The method
      is suitable for high-scale genotyping of clinical HSV-1 isolates and for the
      detection of recombinants.

PMID- 17035493
TI  - Rapid simultaneous detection by real-time PCR of cytomegalovirus UL97 mutations
      in codons 460 and 520 conferring ganciclovir resistance.
AB  - Ganciclovir (GCV) resistance is an emerging problem for transplant recipients. A
      sensitive and rapid real-time PCR approach for simultaneous and semiquantitative
      detection of human cytomegalovirus (HCMV) UL97 mutations in codons 460/520 was
      established by LightCycler and confirmed by restriction fragment length
      polymorphism and sequencing. Results from HCMV laboratory strains were compared
      with results from 11 GCV-resistant clinical isolates.

PMID- 17035492
TI  - tcdC genotypes associated with severe TcdC truncation in an epidemic clone and
      other strains of Clostridium difficile.
AB  - Severe Clostridium difficile associated disease is associated with outbreaks of
      the recently described BI/NAP1 epidemic clone. This clone is characterized by an
      18-bp deletion in the tcdC gene and increased production of toxins A and B in
      vitro. TcdC is a putative negative regulator of toxin A&B production. We
      characterized tcdC genotypes from a collection of C. difficile isolates from a
      hospital that experienced an outbreak caused by the BI/NAP1 epidemic clone.
      Sequence analysis of tcdC was performed on DNA samples isolated from 199
      toxigenic C. difficile isolates (31% BI/NAP1) from 2001 and 2005. Sequences
      obtained from 36 (18.6%) isolates predicted wild-type TcdC (232 amino acid
      residues), whereas 12 (6.1%) isolates had tcdC genotypes with previously
      described 18- or 39-bp deletions. The remaining isolates comprised 15 unique
      genotypes. Of these, 5 genotypes contain 18- or 36-bp deletions. Of these five
      genotypes, one is characterized by a single nucleotide deletion at position 117
      resulting in a frameshift that introduces a stop codon at position 196,
      truncating the predicted TcdC to 65 amino acid residues. All 62 of the isolates
      in this collection comprising the epidemic clone are characterized by this
      genotype. This result suggests that severe truncation of TcdC is responsible for
      the increased toxin production observed in strains belonging to the BI/NAP1 clone
      and that the 18-bp deletion is probably irrelevant to TcdC function. Further
      investigations are required to determine the effect of this and other tcdC
      genotypes on toxin production and clinical disease.

PMID- 17035494
TI  - Feasibility of freeze-dried sera for serological and molecular biological
      detection of hepatitis B and C viruses.
AB  - We compared hepatitis B virus (HBV) surface antigen, anti-hepatitis C virus (HCV)
      antibody, and HCV RNA quantification in frozen and freeze-dried serum samples to
      assess the usefulness of freeze-dried sera for detection of HBV and HCV. The
      results indicated that freeze-dried sera as well as frozen sera can be useful for
      serological and molecular biological analyses of HBV and HCV.

PMID- 17035495
TI  - Molecular method for identification of Rickettsia species in clinical and
      environmental samples.
AB  - We present a PCR method targeting the 23S-5S internal transcribed spacer coupled
      with reverse line blotting that allows Rickettsia species detection and
      identification in a single step. The method is highly sensitive and specific in
      identifying Rickettsia species from both patient and environmental samples. The
      generic approach used allowed us to identify new pathogens.

PMID- 17035496
TI  - Not so pretty in pink: Staphylococcus cohnii masquerading as methicillin
      resistant Staphylococcus aureus on chromogenic media.

PMID- 17035497
TI  - Phylogenetic analysis of "Candidatus Mycoplasma turicensis" isolates from pet
      cats in the United Kingdom, Australia, and South Africa, with analysis of risk
      factors for infection.
AB  - Two hemotropic mycoplasmas have been recognized in cats, Mycoplasma haemofelis
      and "Candidatus Mycoplasma haemominutum." We recently described a third feline
      hemoplasma species, designated "Candidatus Mycoplasma turicensis," in a Swiss cat
      with hemolytic anemia. This isolate induced anemia after experimental
      transmission to two specific-pathogen-free cats and analysis of the 16S rRNA gene
      revealed its close relationship to rodent hemotropic mycoplasmas. The agent was
      recently shown to be prevalent in Swiss pet cats. We sought to investigate the
      presence and clinical importance of "Candidatus Mycoplasma turicensis" infection
      in pet cats outside of Switzerland and to perform the molecular characterization
      of isolates from different countries. A "Candidatus Mycoplasma turicensis"
      specific real-time PCR assay was applied to blood samples from 426 United Kingdom
      (UK), 147 Australian, and 69 South African pet cats. The 16S rRNA genes of
      isolates from different countries were sequenced and signalment and laboratory
      data for the cats were evaluated for associations with "Candidatus Mycoplasma
      turicensis" infection. Infections were detected in samples from UK, Australian,
      and South African pet cats. Infection was associated with the male gender, and
      "Candidatus Mycoplasma haemominutum" and M. haemofelis coinfection. Coinfected
      cats exhibited significantly lower packed cell volume (PCV) values than
      uninfected cats. Phylogenetic analyses revealed that some Australian and South
      African "Candidatus Mycoplasma turicensis" isolates branched away from the
      remaining isolates. In summary, "Candidatus Mycoplasma turicensis" infection in
      pet cats exists over a wide geographical area and significantly decreased PCV
      values are observed in cats coinfected with other feline hemoplasmas.

PMID- 17035499
TI  - Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates
      from China as determined by gyrA mutation analysis using denaturing high-pressure
      liquid chromatography and DNA sequencing.
AB  - A high rate of double point mutations in gyrA (56% of 87 ofloxacin-resistant
      Mycobacterium tuberculosis clinical isolates) indicates the emergence of
      fluoroquinolone resistance. This is the first report to describe denaturing high
      pressure liquid chromatography analysis of mutations in gyrA of M. tuberculosis
      in a large number of clinical isolates.

PMID- 17035498
TI  - Evaluation of Entamoeba histolytica antigen and antibody point-of-care tests for
      the rapid diagnosis of amebiasis.
AB  - The bedside diagnosis of amebiasis could improve patient care. In Bangladesh and
      Vietnam, a novel and simple-to-use Entamoeba histolytica rapid antigen test had
      97% sensitivity and 100% specificity compared to the results of a standard enzyme
      linked immunosorbent assay antigen detection method, and a rapid antibody test
      had 89 to 100% sensitivity and 89 to 95% specificity.

PMID- 17035500
TI  - Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and
      clinical VZV reactivation in hematopoietic stem cell transplantation recipients.
AB  - Reactivation of latent varicella-zoster virus (VZV), presenting as localized
      zoster or as disseminated infection, is a common and potentially serious
      complication in hematopoietic stem cell transplantation (HSCT) recipients. We
      retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence
      hemagglutination method after HSCT and also studied VZV DNA by real-time PCR
      during clinical VZV reactivation using cryopreserved serum samples. No
      significant difference was found between anti-VZV titers in 13 patients with VZV
      infection (localized zoster in 11 patients and disseminated zoster in 2 patients)
      and in 13 subjects without VZV infection at each time point after HSCT.
      Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than
      those of localized zoster cases (P=0.10). Serum VZV DNA copy numbers at the onset
      of disseminated zoster cases tended to be higher than those of localized zoster
      cases (P=0.09). A strong inverse correlation was found between preexisting anti
      VZV titer and serum VZV DNA at onset (r=-0.90, P=0.006). In HSCT recipients,
      preexisting antibody does not prevent the development of VZV reactivation but may
      contribute to decreased viral load at onset, resulting in a mild clinical course.

PMID- 17035502
TI  - Calcium regulation of chloroplast protein translocation is mediated by calmodulin
      binding to Tic32.
AB  - The import of nuclear-encoded proteins into chloroplasts is tightly controlled on
      both sides of the envelope membranes. Regulatory circuits include redox-control
      as well as calcium-regulation, with calmodulin being the likely mediator of the
      latter. Using affinity-chromatography on calmodulin-agarose, we could identify
      the inner envelope translocon component Tic32 as the predominant calmodulin
      binding protein of this membrane. Calmodulin-binding assays corroborate the
      interaction for heterologously expressed as well as native Tic32. The interaction
      is calcium-dependent and is mediated by a calmodulin-binding domain between Leu
      296 and Leu-314 close to the C-proximal end of the pea Tic32. We furthermore
      could establish Tic32 as a bona fide NADPH-dependent dehydrogenase. NADPH but not
      NADH or NADP(+) affects the interaction of Tic110 with Tic32 as well as Tic62. At
      the same time, dehydrogenase activity of Tic32 is affected by calmodulin. In
      particular, binding of NADPH and calmodulin to Tic32 appear to be mutually
      exclusive. These results suggest that redox modulation and calcium regulation of
      chloroplast protein import convene at the Tic translocon and that both could be
      mediated by Tic32.

PMID- 17035501
TI  - Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion,
      embryonic lethality, CNS malformations, and anemia.
AB  - SLC25A19 mutations cause Amish lethal microcephaly (MCPHA), which markedly
      retards brain development and leads to alpha-ketoglutaric aciduria. Previous data
      suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleotide
      transporter. We generated a knockout mouse model of Slc25a19. These animals had
      100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day
      10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a
      yolk sac erythropoietic failure, and elevated alpha-ketoglutarate in the amniotic
      fluid. We found that these animals have normal mitochondrial ribo- and
      deoxyribonucleoside triphosphate levels, suggesting that transport of these
      molecules is not the primary role of SLC25A19. We identified thiamine
      pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through
      homology searching and confirmed it by using transport assays of the recombinant
      reconstituted protein. The mitochondria of Slc25a19(-/-) and MCPHA cells have
      undetectable and markedly reduced ThPP content, respectively. The reduction of
      ThPP levels causes dysfunction of the alpha-ketoglutarate dehydrogenase complex,
      which explains the high levels of this organic acid in MCPHA and suggests that
      mitochondrial ThPP transport is important for CNS development.

PMID- 17035503
TI  - IL-1 resets glucose homeostasis at central levels.
AB  - Administration of IL-1beta results in a profound and long-lasting hypoglycemia.
      Here, we show that this effect can be elicited by endogenous IL-1 and is related
      to not only the capacity of the cytokine to increase glucose uptake in peripheral
      tissues but also to mechanisms integrated in the brain. We show that (i) blockade
      of IL-1 receptors in the brain partially counteracted IL-1-induced hypoglycemia;
      (ii) peripheral administration or induction of IL-1 production resulted in IL
      1beta gene expression in the hypothalamus of normal and insulin-resistant, leptin
      receptor-deficient, diabetic db/db mice; (iii) IL-1-treated normal and db/db mice
      challenged with glucose did not return to their initial glucose levels but
      remained hypoglycemic for several hours. This effect was largely antagonized by
      blockade of IL-1 receptors in the brain; and (iv) when animals with an advanced
      Type II diabetes were treated with IL-1 and challenged with glucose, they died in
      hypoglycemia. However, when IL-1 receptors in the brains of these diabetic mice
      were blocked, they survived, and glucose blood levels approached those that these
      mice had before IL-1 administration. The prolonged hypoglycemic effect of IL-1 is
      insulin-independent and develops against increased levels of glucocorticoids,
      catecholamines, and glucagon. These findings, together with the present
      demonstration that this effect is integrated in the brain and is paralleled by IL
      1beta expression in the hypothalamus, indicate that this cytokine can reset
      glucose homeostasis at central levels. Such reset, along with the peripheral
      actions of the cytokine, would favor glucose uptake by immune cells during
      inflammatory/immune processes.

PMID- 17035504
TI  - Sampling the multiple folding mechanisms of Trp-cage in explicit solvent.
AB  - We investigate the kinetic pathways of folding and unfolding of the designed
      miniprotein Trp- cage in explicit solvent. Straightforward molecular dynamics and
      replica exchange methods both have severe convergence problems, whereas
      transition path sampling allows us to sample unbiased dynamical pathways between
      folded and unfolded states and leads to deeper understanding of the mechanisms of
      (un)folding. In contrast to previous predictions employing an implicit solvent,
      we find that Trp-cage folds primarily (80% of the paths) via a pathway forming
      the tertiary contacts and the salt bridge, before helix formation. The remaining
      20% of the paths occur in the opposite order, by first forming the helix. The
      transition states of the rate-limiting steps are solvated native-like structures.
      Water expulsion is found to be the last step upon folding for each route.
      Committor analysis suggests that the dynamics of the solvent is not part of the
      reaction coordinate. Nevertheless, during the transition, specific water
      molecules are strongly bound and can play a structural role in the folding.

PMID- 17035505
TI  - Chemical screening methods to identify ligands that promote protein stability,
      protein crystallization, and structure determination.
AB  - The 3D structures of human therapeutic targets are enabling for drug discovery.
      However, their purification and crystallization remain rate determining. In
      individual cases, ligands have been used to increase the success rate of protein
      purification and crystallization, but the broad applicability of this approach is
      unknown. We implemented two screening platforms, based on either fluorimetry or
      static light scattering, to measure the increase in protein thermal stability
      upon binding of a ligand without the need to monitor enzyme activity. In total,
      221 different proteins from humans and human parasites were screened against one
      or both of two sorts of small-molecule libraries. The first library comprised
      different salts, pH conditions, and commonly found small molecules and was
      applicable to all proteins. The second comprised compounds specific for protein
      families of particular interest (e.g., protein kinases). In 20 cases, including
      nine unique human protein kinases, a small molecule was identified that
      stabilized the proteins and promoted structure determination. The methods are
      cost-effective, can be implemented in any laboratory, promise to increase the
      success rates of purifying and crystallizing human proteins significantly, and
      identify new ligands for these proteins.

PMID- 17035506
TI  - The distance that kinesin-1 holds its cargo from the microtubule surface measured
      by fluorescence interference contrast microscopy.
AB  - Kinesin-1 is a motor protein that carries cellular cargo such as membrane-bounded
      organelles along microtubules (MTs). The homodimeric motor molecule contains two
      N-terminal motor domains (the motor "heads"), a long coiled-coil domain (the
      "rod" or "stalk"), and two small globular "tail" domains. Much has been learned
      about how kinesin's heads step along a MT and how the tail is involved in cargo
      binding and autoinhibition. However, little is known about the role of the rod.
      Here, we investigate the extension of the rod during active transport by
      measuring the height at which MTs glide over a kinesin-coated surface in the
      presence of ATP. To perform height measurements with nanometer precision, we used
      fluorescence interference contrast microscopy, which is based on the self
      interference of fluorescent light from objects near a reflecting surface. Using
      an in situ calibrating method, we determined that kinesin-1 molecules elevate
      gliding MTs 17 +/- 2 nm (mean +/- SEM) above the surface. When varying the
      composition of the surrounding nucleotides or removing the negatively charged 
      COOH termini of the MTs by subtilisin digestion, we found no significant changes
      in the measured distance. Even though this distance is significantly shorter than
      the contour length of the motor molecule ( approximately 60 nm), it may be
      sufficient to prevent proteins bound to the MTs or prevent the organelles from
      interfering with transport.

PMID- 17035507
TI  - The effect of intensive lipid lowering on coronary atheroma and clinical outcome.
AB  - The association between raised plasma cholesterol and cardiovascular risk is well
      established, with consistent evidence associating LDL-cholesterol reduction with
      a reduction in primary and secondary cardiovascular events. It is believed that
      intensive lipid lowering may improve clinical outcomes further by acting to
      stabilise plaque and preventing plaque progression, ultimately reducing plaque
      vulnerability. However, it remains uncertain whether a continued clinical benefit
      occurs with intensive lipid lowering or if there is a threshold level below which
      no further benefit occurs.

PMID- 17035508
TI  - Transcatheter closure of perimembranous ventricular septal defect: is the risk of
      heart block too high a price?
AB  - The late development of heart block in paediatric patients following device
      closure of a perimembranous ventricular septal defect may be a cause for concern.

PMID- 17035509
TI  - Antithrombotic treatment for peripheral arterial disease.
AB  - CONTEXT: Patients with peripheral arterial disease (PAD) bear a substantial risk
      for vascular events in the coronary, cerebral and peripheral circulations. In
      addition, this disorder is associated with a systemic milieu characterised by
      ongoing platelet activation and heightened thrombogenesis. OBJECTIVE: To
      determine the optimal antithrombotic prophylaxis for patients with PAD. DATA
      SOURCES: Using terms related to PAD and antithrombotic agents, we searched the
      following databases for relevant articles: MEDLINE, EMBASE, the Cochrane Central
      Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the
      National Institutes of Health Clinical Trials Database, Web of Science, and the
      International Pharmaceutical Abstracts Database (search dates: 1 January 1990 to
      1 January 2007). Additional articles were identified from cardiovascular and
      vascular surgery conference proceedings, bibliographies of review articles, and
      personal files. STUDY SELECTION: We focused on randomised trials, systematic
      reviews and consensus guidelines of antithrombotic therapies for PAD. DATA
      EXTRACTION: Detailed study information was abstracted by each author working
      independently. RESULTS: Multiple studies show that patients with PAD manifest
      platelet hyperaggregability, increased levels of soluble platelet activation
      markers, enhanced thrombin generation and altered fibrinolytic potential. Many of
      these markers predict subsequent cardiovascular events. Available randomised
      trials and meta-analyses show that most available antithrombotic agents prevent
      major cardiovascular events and death in patients with PAD, including aspirin,
      aspirin/dipyridamole, clopidogrel, ticlopidine, picotamide and oral
      anticoagulants. CONCLUSIONS: Although the most favourable risk-benefit profile,
      cost-effectiveness and overall evidence base supports aspirin in this setting, we
      provide scenarios in which alternatives to aspirin should be considered.

PMID- 17035510
TI  - Biocompatibility of septal defect closure devices.
AB  - OBJECTIVE: Despite their clinical introduction 10 years ago, no human series on
      the healing response to Amplatzer and Starflex devices in humans have been
      reported yet. We sought to investigate the biocompatibility of Amplatzer and
      Cardioseal/Starflex septal occluder devices in humans and compare the findings to
      results in experimental animals. METHODS: The healing response of Amplatzer and
      Cardioseal/Starflex septal occluder devices in humans (n = 12, follow-up periods
      from 5 days to 4 years) and in experimental animals (n = 32, follow-up periods
      from 4 days to 1 year) was studied using a uniform work up protocol. Histological
      sections of paraffin-wax-embedded or methacrylate-embedded specimen and scanning
      electron microscopy were used for biocompatibility screening. RESULTS:
      Neoendothelialisation of all examined devices was complete after 3 months in
      vivo. Protruding metal frame parts, like screw threads and spring arms, were
      covered last. The initial deposition of fibrin and blood cells on the polyester
      fabric was subsequently organised by ingrown fibroblastic cells. Loosely arranged
      and poorly vascularised young granulation tissue was transformed time-dependently
      into quiescent fibre-rich connective repair tissue poor of cellular and capillary
      vessel components. Consistently, a mild chronic inflammatory response directed
      against textile fibres of both types of implants characterised by lymphocytic
      infiltration and multinucleated foreign body giant cells was observed equally in
      human and animal explants. CONCLUSIONS: Systematic biocompatibility screening in
      a series of explanted human septal occluder devices showed results corresponding
      to findings in animal studies with regard to neoendothelialisation, cellular
      organisation of initial thrombus and persisting immune response.

PMID- 17035511
TI  - Pregnancy and the various forms of the Fontan circulation.
AB  - The Fontan operation is performed on those with highly complex congenital heart
      disease and has improved the survival and quality of life of such patients.
      Inevitably there are late complications secondary to extensive surgery and long
      term survival estimates are about 70% at 10 years and 60-63% at 15 years.
      Pregnancy therefore requires careful prior consideration. However, the opinion
      that that pregnancy is not advisable for the Fontan patient is somewhat
      contentious and maybe an oversimplification of what is a highly emotive and
      complex issue.

PMID- 17035512
TI  - Diagnosis of Paracoccidioidomycosis by detection of antigen and antibody in
      bronchoalveolar lavage fluids.
AB  - Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus
      Paracoccidioides brasiliensis and is believed to be the leading cause of fungal
      pulmonary infection. In this study, we used an inhibition enzyme-linked
      immunosorbent assay to diagnose pulmonary PCM based on the detection of 43-kDa
      and 70-kDa molecules in bronchoalveolar lavage fluids. The results were compared
      with results obtained by classical methods for antibody detection.

PMID- 17035513
TI  - Multiplex assay for simultaneous measurement of antibodies to multiple Plasmodium
      falciparum antigens.
AB  - Antibodies to Plasmodium falciparum are classically measured using the enzyme
      linked immunosorbent assay (ELISA). Although highly sensitive, this technique is
      labor-intensive when large numbers of samples must be screened against multiple
      antigens. The suspension array technology (SAT) might be an alterative to ELISA,
      as it allows measurement of antibodies against multiple antigens simultaneously
      with a small volume of sample. This study sought to adapt the new SAT multiplex
      system for measuring antibodies against nine malarial vaccine candidate antigens,
      including recombinant proteins from two variants of merozoite surface protein 1,
      two variants of apical merozoite antigen 1, erythrocyte binding antigen 175,
      merozoite surface protein 3, and peptides from the circumsporozoite protein, ring
      erythrocyte surface antigen, and liver-stage antigen 1. Various concentrations of
      the antigens were coupled to microspheres with different spectral addresses, and
      plasma samples from Cameroonian adults were screened by SAT in mono- and
      multiplex formats and by ELISA. Optimal amounts of protein required to perform
      the SAT assay were 10- to 100-fold less than that needed for ELISA. Excellent
      agreement was found between the single and multiplex formats (R > or = 0.96),
      even when two variants of the same antigen were used. The multiplex assay was
      rapid, reproducible, required less than 1 mul of plasma, and had a good
      correlation with ELISA. Thus, SAT provides an important new tool for studying the
      immune response to malaria rapidly and efficiently in large populations, even
      when the amount of plasma available is limited, e.g., in studies of neonates or
      finger-prick blood.

PMID- 17035514
TI  - The National Institutes of Health Blueprint for Neuroscience Research.

PMID- 17035515
TI  - Estrogen, menopause, and the aging brain: how basic neuroscience can inform
      hormone therapy in women.

PMID- 17035516
TI  - Disease-modifying pathways in neurodegeneration.

PMID- 17035517
TI  - Developmental plasticity of inhibitory circuitry.

PMID- 17035518
TI  - Cellular excitability and the regulation of functional neuronal identity: from
      gene expression to neuromodulation.

PMID- 17035519
TI  - Influencing and interpreting visual input: the role of a visual feedback system.

PMID- 17035520
TI  - Addiction and arousal: alternative roles of hypothalamic peptides.
AB  - The importance of the lateral hypothalamus in the regulation of reward and
      motivation has long been recognized. However, the neuronal network involved in
      such a hypothalamic regulation of reward remains essentially unknown. Recently,
      hypocretin-containing neurons, a group of hypothalamic neurons known to be
      associated with the stability of arousal, have emerged as important structures in
      the control of brain reward function. This review summarizes a Mini-Symposium
      presented at the 2006 Annual Meeting of the Society for Neuroscience.

PMID- 17035521
TI  - Singing mice, songbirds, and more: models for FOXP2 function and dysfunction in
      human speech and language.
AB  - In 2001, a point mutation in the forkhead box P2 (FOXP2) coding sequence was
      identified as the basis of an inherited speech and language disorder suffered by
      members of the family known as "KE." This mini-symposium review focuses on recent
      findings and research-in-progress, primarily from five laboratories. Each aims at
      capitalizing on the FOXP2 discovery to build a neurobiological bridge between
      molecule and phenotype. Below, we describe genetic through behavioral techniques
      used currently to investigate FoxP2 in birds, rodents, and humans for discovery
      of the neural bases of vocal learning and language.

PMID- 17035523
TI  - Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor
      actions on anxiety through alterations of serotonin activity.
AB  - The effects of PD 176252 [3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)
      cyclohexylmethyl]-2-methyl-2-[3-(nitro-phenyl)ureido]propionamide], a nonpeptide
      bombesin (BB) BB1/BB2 receptor antagonist, were assessed in rats using several
      ethologically relevant tests of anxiety. Consistent with a role for the bombesin
      family of peptides in subserving anxiety behaviors, the antagonist increased
      social interaction (3.75 and 7.5 mg/kg, i.p.), dose-dependently attenuated the
      number of vocalizations emitted by guinea pig pups separated from their mother (1
      30 mg/kg, i.p.), reduced latency to approach a palatable snack in an anxiogenic
      (unfamiliar) environment, and reduced the fear-potentiated startle response (5
      and 10 mg/kg, i.p., and 100-200 ng per rat, i.c.v.). When administered directly
      to the dorsal raphe nucleus (DRN), PD 176252 (20-500 ng) increased social
      interaction under aversive conditions, as did the 5-HT1A receptor agonist 8
      hydroxy-2(di-n-propylamino)tetralin (50 ng). Furthermore, intra-DRN microinfusion
      of the peptide antagonist (PD 176252) suppressed, whereas its agonist [neuromedin
      B (NMB)-30] promoted, the in vivo release of 5-HT in the ventral hippocampus. In
      parallel, the suppressed social interaction elicited by intra-DRN administration
      of NMB was attenuated by a systemically administered 5-HT2C (but not 5-HT1A)
      receptor antagonist. Together, these findings suggest that endogenous BB-like
      peptides at the DRN evoke the release of 5-HT from the limbic nerve terminals
      originating from the raphe, specifically at the ventral hippocampus, resulting in
      anxiogenesis. The finding that this action was attenuated by BB receptor (BB1
      and/or BB2) antagonists suggests that these compounds may represent a novel class
      of anxiolytic agents.

PMID- 17035522
TI  - Next-generation optical technologies for illuminating genetically targeted brain
      circuits.
AB  - Emerging technologies from optics, genetics, and bioengineering are being
      combined for studies of intact neural circuits. The rapid progression of such
      interdisciplinary "optogenetic" approaches has expanded capabilities for optical
      imaging and genetic targeting of specific cell types. Here we explore key recent
      advances that unite optical and genetic approaches, focusing on promising
      techniques that either allow novel studies of neural dynamics and behavior or
      provide fresh perspectives on classic model systems.

PMID- 17035524
TI  - Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for
      tRNA-charging enzymes in peripheral axons.
AB  - Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy
      type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more
      severe in the upper extremities. We previously implicated mutations in the gene
      encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is
      a member of the family of aminoacyl-tRNA synthetases responsible for charging
      tRNA with cognate amino acids; GARS ligates glycine to tRNA(Gly). Here, we
      present functional analyses of disease-associated GARS mutations and show that
      there are not any significant mutation-associated changes in GARS expression
      levels; that the majority of identified GARS mutations modeled in yeast severely
      impair viability; and that, in most cases, mutant GARS protein mislocalizes in
      neuronal cells. Indeed, four of the five mutations studied show loss-of-function
      features in at least one assay, suggesting that tRNA-charging deficits play a
      role in disease pathogenesis. Finally, we detected endogenous GARS-associated
      granules in the neurite projections of cultured neurons and in the peripheral
      nerve axons of normal human tissue. These data are particularly important in
      light of the recent identification of CMT-associated mutations in another tRNA
      synthetase gene [YARS (tyrosyl-tRNA synthetase gene)]. Together, these findings
      suggest that tRNA-charging enzymes play a key role in maintaining peripheral
      axons.

PMID- 17035525
TI  - Oligomerization of KCC2 correlates with development of inhibitory
      neurotransmission.
AB  - The neuron-specific K+-Cl- cotransporter KCC2 extrudes Cl- and renders GABA and
      glycine action hyperpolarizing. Thus, it plays a pivotal role in neuronal
      inhibition. Development-dependent KCC2 activation is regulated at the
      transcriptional level and by unknown posttranslational mechanisms. Here, we
      analyzed KCC2 activation at the protein level in the developing rat lateral
      superior olive (LSO), a prominent auditory brainstem structure. Electrophysiology
      demonstrated ineffective KCC2-mediated Cl- extrusion in LSO neurons at postnatal
      day 3 (P3). Immunohistochemical analyses by confocal and electron microscopy
      revealed KCC2 signals at the plasma membrane in the somata and dendrites of both
      immature and mature neurons. Biochemical analysis demonstrated mature
      glycosylation pattern of KCC2 at both stages. Immunoblot analysis of the immature
      brainstem demonstrated mainly monomeric KCC2. In contrast, three KCC2 oligomers
      with molecular masses of approximately 270, approximately 400, and approximately
      500 kDa were identified in the mature brainstem. These oligomers were sensitive
      to sulfhydryl-reducing agents and resistant to SDS, contrary to the situation
      seen in the related Na+-(K+)-Cl- cotransporter. In HEK-293 cells, coexpressed
      hemagglutinin-tagged KCC2 assembled with histidine-tagged KCC2, demonstrating
      formation of homomers. Based on these findings, we conclude that the oligomers
      represent KCC2 dimers, trimers, and tetramers. Finally, immunoblot analysis
      identified a development-dependent increase in the oligomer/monomer ratio from
      embryonic day 18 to P30 throughout the brain that correlates with KCC2
      activation. Together, our data indicate that the developmental shift from
      depolarization to hyperpolarization can be determined by both increased gene
      expression and KCC2 oligomerization.

PMID- 17035526
TI  - Learning rules for spike timing-dependent plasticity depend on dendritic synapse
      location.
AB  - Previous studies focusing on the temporal rules governing changes in synaptic
      strength during spike timing-dependent synaptic plasticity (STDP) have paid
      little attention to the fact that synaptic inputs are distributed across complex
      dendritic trees. During STDP, propagation of action potentials (APs) back to the
      site of synaptic input is thought to trigger plasticity. However, in pyramidal
      neurons, backpropagation of single APs is decremental, whereas high-frequency
      bursts lead to generation of distal dendritic calcium spikes. This raises the
      question whether STDP learning rules depend on synapse location and firing mode.
      Here, we investigate this issue at synapses between layer 2/3 and layer 5
      pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of
      single APs at positive times leads to a distance-dependent shift to long-term
      depression (LTD) at distal inputs. At proximal sites, this LTD could be converted
      to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for
      BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a
      progressive, distance-dependent shift in the timing requirements for induction of
      LTP and LTD, such that distal synapses display novel timing rules: they
      potentiate when inputs are activated after burst onset (negative timing) but
      depress when activated before burst onset (positive timing). These findings could
      be explained by distance-dependent differences in the underlying dendritic
      voltage waveforms driving NMDA receptor activation during STDP induction. Our
      results suggest that synapse location within the dendritic tree is a crucial
      determinant of STDP, and that synapses undergo plasticity according to local
      rather than global learning rules.

PMID- 17035527
TI  - Intracellular zinc elevation measured with a "calcium-specific" indicator during
      ischemia and reperfusion in rat hippocampus: a question on calcium overload.
AB  - Much of our current evidence concerning of the role of calcium (Ca2+) as a second
      messenger comes from its interaction with fluorescent probes; however, many Ca2+
      probes also have a higher affinity for another divalent cation: zinc (Zn2+). In
      this study, using a selective Zn2+ probe (Newport Green), we investigated the
      accumulation of intracellular Zn2+ transients in acute rat hippocampal slices
      during ischemia, simulated by oxygen and glucose deprivation (OGD). Subsequent
      reperfusion with glucose-containing oxygenated medium resulted in an additional
      increase in intracellular Zn2+. Such observations compelled us to investigate the
      contribution of Zn2+ to the alleged intracellular Ca2+ overload occurring in
      ischemia and reperfusion. Using confocal fluorescent microscopy of Calcium Green
      1, a widely used Ca2+ indicator, we detected increases in fluorescence intensity
      during OGD and reperfusion. However, application of a Zn2+ chelator, at the peak
      of the fluorescence elevation (interpreted as Ca2+ overload), resulted in a
      significant drop in intensity, suggesting that rising Zn2+ is the primary source
      of the increasing Calcium Green-1 fluorescence. Finally, staining with the cell
      viability indicator propidium iodide revealed that Zn2+ is responsible for the
      ischemic neuronal cell death, because Zn2+ chelation prevented cells from
      sustaining ischemic damage. Current cellular models of ischemic injury center on
      Ca2+-mediated excitotoxicity. Our results indicate that Zn2+ elevation
      contributes to conventionally recognized Ca2+ overload and also suggest that the
      role of Ca2+ in neurotoxicity described previously using Ca2+ probes may need to
      be re-examined to determine whether effect previously attributed to Ca2+ could,
      in part, be attributable to Zn2+.

PMID- 17035528
TI  - The transcription factor six1 inhibits neuronal and promotes hair cell fate in
      the developing zebrafish (Danio rerio) inner ear.
AB  - The developmental processes leading to the differentiation of mechanosensory hair
      cells and statoacoustic ganglion neurons from the early otic epithelium remain
      unclear. Possible candidates include members of the Pax-Six-Eya-Dach (paired box
      sine oculis homeobox-eyes absent-dachshund) gene regulatory network. We cloned
      zebrafish six1 and studied its function in inner ear development. Gain- and loss
      of-function experiments show that six1 has opposing roles in hair cell and
      neuronal lineages. It promotes hair cell fate and, conversely, inhibits neuronal
      fate by differentially affecting cell proliferation and cell death in these
      lineages. By independently targeting hair cells with atoh1a (atonal homolog 1a)
      knockdown or neurons with neurog1 (neurogenin 1) knockdown, we showed that the
      remaining cell population, neurons or hair cells, respectively, is still affected
      by gain or loss of six1 function. six1 interacts with other members of the Pax
      Six-Eya-Dach regulatory network, in particular dacha and dachb in the hair cell
      but not neuronal lineage. Unlike in mouse, six1 does not appear to be dependent
      on eya1, although it seems to be important for the regulation of eya1 and pax2b
      expression in the ventral otic epithelium. Furthermore, six1 expression appears
      to be regulated by pax2b and also by foxi1 (forkhead box I1) as expected for an
      early inducer of the otic placode. Our results are the first to demonstrate a
      dual role for a member of the Pax-Six-Eya-Dach regulatory network in inner ear
      development.

PMID- 17035529
TI  - A progressive and cell non-autonomous increase in striatal neural stem cells in
      the Huntington's disease R6/2 mouse.
AB  - Neural stem and progenitor cells are located in the subependyma of the adult
      forebrain. An increase in adult subependymal cell proliferation is reported after
      various kinds of brain injury. We demonstrate an expansion of neural precursor
      cells in the postnatal subependyma in a murine genetic disease model of
      Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay
      as an index of the number of neural stem cells in vivo and to assess
      proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess
      the progenitor cell population and their fates. Disease progression in this model
      leads to an increase in the numbers of neural stem cells in the adult striatal
      subependyma. This increase is produced cell non-autonomously by events in the
      R6/2 brains as the mice become increasingly symptomatic. Once the neural stem
      cell increase is induced in vivo, it is maintained during in vitro passaging of
      neural stem cells, but the neural stem cell increase is not reproduced during in
      vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition,
      we show that some of the R6/2 neural progenitor cells show a change from their
      normal migration destiny toward the olfactory bulb. Instead, some of these cells
      migrate into the striatum, one of the main affected areas in HD. Our findings
      demonstrate that HD damage recruits precursor cells in two ways: expansion of
      neural stem cells and altered migration of progenitor cells.

PMID- 17035530
TI  - Different mechanisms exist for the plasticity of glutamate reuptake during early
      long-term potentiation (LTP) and late LTP.
AB  - Regulation of glutamate reuptake occurs along with several forms of synaptic
      plasticity. These associations led to the hypothesis that regulation of glutamate
      uptake is a general component of plasticity at glutamatergic synapses. We tested
      this hypothesis by determining whether glutamate uptake is regulated during both
      the early phases (E-LTP) and late phases (L-LTP) of long-term potentiation (LTP).
      We found that glutamate uptake was rapidly increased within minutes after
      induction of LTP and that the increase in glutamate uptake persisted for at least
      3 h in CA1 of the hippocampus. NMDA receptor activation and Na+-dependent high
      affinity glutamate transporters were responsible for the regulation of glutamate
      uptake during all phases of LTP. However, different mechanisms appear to be
      responsible for the increase in glutamate uptake during E-LTP and L-LTP. The
      increase in glutamate uptake observed during E-LTP did not require new protein
      synthesis, was mediated by PKC but not cAMP, and as previously shown was
      attributable to EAAC1 (excitatory amino acid carrier-1), a neuronal glutamate
      transporter. On the other hand, the increase in glutamate uptake during L-LTP
      required new protein synthesis and was mediated by the cAMP-PKA (protein kinase
      A) pathway, and it involved a different glutamate transporter, GLT1a (glutamate
      transporter subtype 1a). The switch in mechanisms regulating glutamate uptake
      between E-LTP and L-LTP paralleled the differences in the mechanisms responsible
      for the induction of E-LTP and L-LTP. Moreover, the differences in signaling
      pathways and transporters involved in regulating glutamate uptake during E-LTP
      and L-LTP indicate that different functions and/or sites may exist for the
      changes in glutamate uptake during E-LTP and L-LTP.

PMID- 17035531
TI  - Adenosinergic mechanisms contribute to individual differences in sleep
      deprivation-induced changes in neurobehavioral function and brain rhythmic
      activity.
AB  - Large individual differences characterize the changes induced by sleep
      deprivation on neurobehavioral functions and rhythmic brain activity. To
      investigate adenosinergic mechanisms in these differences, we studied the effects
      of prolonged waking and the adenosine receptor antagonist caffeine on sustained
      vigilant attention and regional electroencephalogram (EEG) power in the ranges of
      theta activity (6.25-8.25 Hz) in waking and the slow oscillation (<1 Hz) in
      sleep. Activity in these frequencies is functionally related to sleep
      deprivation. In 12 subjectively caffeine-sensitive and 10 -insensitive young men,
      psychomotor vigilance task (PVT) performance and EEG were assessed at 3 h
      intervals before, during, and after one night without sleep. After 11 and 23 h
      waking, subjects received 200 mg caffeine and placebo in double-blind, cross-over
      manner. In the placebo condition, sleep deprivation impaired PVT speed more in
      caffeine-sensitive than in caffeine-insensitive men. This difference was
      counteracted by caffeine. Theta power in waking increased more in a frontal EEG
      derivation than in a posterior derivation. Caffeine attenuated this power
      gradient in caffeine sensitive subjects. Sleep loss also differently affected the
      power distribution <1 Hz in non-rapid eye movement sleep between caffeine
      sensitive and insensitive subjects. Also, this difference was mirrored by the
      action of caffeine. The effects of sleep deprivation and caffeine on sustained
      attention and regional EEG power in waking and sleep were inversely related.
      These findings suggest that adenosinergic mechanisms contribute to individual
      differences in waking-induced impairment of neurobehavioral performance and
      functional aspects of EEG topography associated with sleep deprivation.

PMID- 17035532
TI  - Acute impairment of mitochondrial trafficking by beta-amyloid peptides in
      hippocampal neurons.
AB  - Defects in axonal transport are often associated with a wide variety of
      neurological diseases including Alzheimer's disease (AD). Beta-amyloid (Abeta) is
      a major component of neuritic plaques associated with pathological conditions of
      AD brains. Here, we report that a brief exposure of cultured hippocampal neurons
      to Abeta molecules resulted in rapid and severe impairment of mitochondrial
      transport without inducing apparent cell death and significant morphological
      changes. Such acute inhibition of mitochondrial transport was not associated with
      a disruption of mitochondria potential nor involved aberrant cytoskeletal
      changes. Abeta also did not elicit significant Ca2+ signaling to affect
      mitochondrial trafficking. However, stimulation of protein kinase A (PKA) by
      forskolin, cAMP analogs, or neuropeptides effectively alleviated the impairment.
      We also show that Abeta inhibited mitochondrial transport by acting through
      glycogen synthase kinase 3beta (GSK3beta). Given that mitochondria are crucial
      organelles for many cellular functions and survival, our findings thus identify
      an important acute action of Abeta molecules on nerve cells that could
      potentially contribute to various abnormalities of neuronal functions under AD
      conditions. Manipulation of GSK3beta and PKA activities may represent a key
      approach for preventing and alleviating Abeta cytotoxicity and AD pathological
      conditions.

PMID- 17035533
TI  - Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses
      in rat hippocampal neurons.
AB  - We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by
      electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal
      neurons from rat hippocampal slices. Acute application of CX3CL1 caused a
      sustained reduction of EPSC amplitude, with partial recovery after washout.
      CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse
      ratio was maintained, amplitude distribution of spontaneous excitatory
      postsynaptic currents shifted to lower values, and whole-cell current responses
      to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by
      CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude
      in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of
      both EPSC and AMPA current was not observed in the absence of afferent fiber
      stimulation or AMPA receptor activation, respectively, indicating the requirement
      of sustained receptor activity for its development. Findings obtained from
      hippocampal slices, cultured hippocampal neurons, and transfected human embryonic
      kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is
      likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced
      depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase
      inhibitors, and pertussis toxin (PTX); (2) CX3CL1 inhibited forskolin-induced
      cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced
      Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+
      and phosphatase activity. Together, these findings indicate that CX3CL1
      negatively modulates AMPA receptor function at active glutamatergic synapses
      through cell-signaling pathways by influencing the balance between kinase and
      phosphatase activity.

PMID- 17035534
TI  - Deletion of annexin 2 light chain p11 in nociceptors causes deficits in
      somatosensory coding and pain behavior.
AB  - The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the
      trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid
      sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion
      channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as
      well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor.
      To evaluate the role of p11 in peripheral pain pathways, we generated a loxP
      flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11
      exclusively from nociceptive primary sensory neurons in mice. p11-null neurons
      showed deficits in the expression of Na(V)1.8, but not of annexin 2. Damage
      sensing primary neurons from these animals show a reduced tetrodotoxin-resistant
      sodium current density, consistent with a loss of membrane-associated Na(V)1.8.
      Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly
      compromised. Acute pain behavior was attenuated in certain models, but no
      deficits in inflammatory pain were observed. A significant deficit in neuropathic
      pain behavior was also apparent in the conditional-null mice. These results
      confirm an important role for p11 in nociceptor function.

PMID- 17035535
TI  - Olfactory discrimination learning increases the survival of adult-born neurons in
      the olfactory bulb.
AB  - In the olfactory bulb (OB), new neurons are added throughout life, forming an
      integral part of the functioning circuit. Yet only some of them survive more than
      a month. To determine whether this turnover depends on olfactory learning, we
      examined the survival of adult newborn cells labeled with the cell division
      marker BrdU, administered before learning in an olfactory discrimination task. We
      report that discrimination learning increases the number of newborn neurons in
      the adult OB by prolonging their survival. Simple exposure to the pair of
      olfactory cues did not alter neurogenesis, indicating that the mere activation of
      sensory inputs during the learning task was insufficient to alter neurogenesis.
      The increase in cell survival after learning was not uniformly distributed
      throughout angular sectors of coronal sections of the OB. Monitoring odor
      activation maps using patterns of Zif268 immediate early gene expression revealed
      that survival was greater in regions more activated by the non-reinforced
      odorant. We conclude that sensory activation in a learning context not only
      controls the total number of newborn neurons in the adult OB, but also refines
      their precise location. Shaping the distribution of newborn neurons by
      influencing their survival could optimize the olfactory information processing
      required for odor discrimination.

PMID- 17035536
TI  - Cystine/glutamate exchange modulates glutathione supply for neuroprotection from
      oxidative stress and cell proliferation.
AB  - The cystine/glutamate exchanger (xCT) provides intracellular cyst(e)ine for
      production of glutathione, a major cellular antioxidant. Using xCT overexpression
      and underexpression, we present evidence that xCT-dependent glutathione
      production modulates both neuroprotection from oxidative stress and cell
      proliferation. In embryonic and adult rat brain, xCT protein was enriched at the
      CSF-brain barrier (i.e., meninges) and also expressed in the cortex, hippocampus,
      striatum, and cerebellum. To examine the neuroprotective role of xCT, various non
      neuronal cell types (astrocytes, meningeal cells, and peripheral fibroblasts)
      were cocultured with immature cortical neurons and exposed to oxidative glutamate
      toxicity, a model involving glutathione depletion. Cultured meningeal cells,
      which naturally maintain high xCT expression, were more neuroprotective than
      astrocytes. Selective xCT overexpression in astrocytes was sufficient to enhance
      glutathione synthesis/release and confer potent glutathione-dependent
      neuroprotection from oxidative stress. Moreover, normally nonprotective
      fibroblasts could be re-engineered to be neuroprotective with ectopic xCT
      overexpression indicating that xCT is a key step in the pathway to glutathione
      synthesis. Conversely, astrocytes and meningeal cells derived from sut/sut mice
      (xCT loss-of-function mutants) showed greatly reduced proliferation in culture
      attributable to increased oxidative stress and thiol deficiency, because growth
      could be rescued by the thiol-donor beta-mercaptoethanol. Strikingly, sut/sut
      mice developed brain atrophy by early adulthood, exhibiting ventricular
      enlargement, thinning of the cortex, and shrinkage of the striatum. Our results
      indicate that xCT can provide neuroprotection by enhancing glutathione export
      from non-neuronal cells such as astrocytes and meningeal cells. Furthermore, xCT
      is critical for cell proliferation during development in vitro and possibly in
      vivo.

PMID- 17035537
TI  - Neuronal responses to object images in the macaque inferotemporal cortex at
      different stimulus discrimination levels.
AB  - We can discriminate visual objects at multiple levels, from coarse categorization
      to individual identification. It is not known how the brain adapts to the varying
      levels of discrimination required in different behavioral contexts. In the
      present study, we investigated whether the stimulus selectivity of neuronal
      responses in the monkey inferotemporal cortex, which is the final unimodal stage
      in the ventral visual pathway, changes with the varying levels of discrimination
      required for different task conditions. Responses of each inferotemporal cell to
      the same set of nine object images were examined in two different task
      conditions. The task alternated between coarse and fine discriminations in the
      first experiment, and the rule alternated between categorization and individual
      object identification in the second experiment. Despite these changes in the task
      requirements and the resulting differences in the monkeys' behavior, we found
      that the responses of inferotemporal cells were largely unchanged in both
      experiments. Our results suggest that representation of object images in the
      inferotemporal cortex is stable and rather insensitive to these kinds of shifts
      in behavioral context. Neuronal adaptations to behavioral context may occur
      downstream of the inferotemporal cortex.

PMID- 17035538
TI  - p25/cyclin-dependent kinase 5 induces production and intraneuronal accumulation
      of amyloid beta in vivo.
AB  - Aberrant processing of the amyloid precursor protein (APP) and the subsequent
      accumulation of amyloid beta (Abeta) peptide has been widely established as a
      central event in Alzheimer's disease (AD) pathogenesis. The sequential cleavage
      steps required for the generation of Abeta are well outlined; however, there is a
      relative dearth of knowledge pertaining to signaling pathways and molecular
      mechanisms that can modulate this process. Here, we demonstrate a novel role for
      p25/cyclin-dependent kinase 5 (Cdk5) in regulating APP processing, Abeta peptide
      generation, and intraneuronal Abeta accumulation in inducible p25 transgenic and
      compound PD-APP transgenic mouse models that demonstrate deregulated Cdk5
      activity and a neurodegenerative phenotype. Induction of p25 resulted in enhanced
      forebrain Abeta levels before any evidence of neuropathology in these mice.
      Intracellular Abeta accumulated in perinuclear regions and distended axons within
      the forebrains of these mice. Evidence for modulations in axonal transport or
      beta-site APP cleaving enzyme 1 protein levels and activity are presented as
      mechanisms that may account for the Abeta accumulation caused by p25/Cdk5
      deregulation. Collectively, these findings delineate a novel pathological
      mechanism involving aberrant APP processing by p25/Cdk5 and have important
      implications in AD pathogenesis.

PMID- 17035539
TI  - A behavioral role for feature detection by sensory bursts.
AB  - Brief episodes of high-frequency firing of sensory neurons, or bursts, occur in
      many systems, including mammalian auditory and visual systems, and are believed
      to signal the occurrence of particularly important stimulus features, i.e., to
      function as feature detectors. However, the behavioral relevance of sensory
      bursts has not been established in any system. Here, we show that bursts in an
      identified auditory interneuron of crickets reliably signal salient stimulus
      features and reliably predict behavioral responses. Our results thus demonstrate
      the close link between sensory bursts and behavior.

PMID- 17035540
TI  - Angular tuning bias of vibrissa-responsive cells in the paralemniscal pathway.
AB  - One of the most salient features of primary vibrissal afferents is their
      sensitivity to the direction in which the vibrissae move. Directional sensitivity
      is also well conserved in brainstem, thalamic, and cortical neurons of the
      lemniscal pathway, indicating that this property plays a key role in the
      organization of the vibrissal system. Here, we show that directional tuning is
      also a fundamental feature of second-order interpolaris neurons that give rise to
      the paralemniscal pathway. Quantitative assessment of responses to vibrissa
      deflection revealed an anisotropic organization of receptive fields with regard
      to topography, response magnitude, and the degree of angular tuning. Responses
      evoked by all vibrissae within the receptive field of each cell exhibited a high
      consistency of direction preference, but a striking difference in angular tuning
      preference was found among cells that reside in the rostral and caudal divisions
      of the interpolaris nucleus. Although in caudal interpolaris vectors of angular
      preference pointed in all directions, in rostral interpolaris virtually all
      vectors pointed upward, revealing a strong preference for this direction. Control
      experiments showed that the upward bias did not rely on a preferential
      innervation of rostral cells by upwardly tuned primary vibrissa afferents, nor
      did it rely on a direction-selective recruitment of feedforward inhibition. We
      thus propose that the upward preference bias of rostral cells, which project to
      the posterior group of the thalamus, emerges from use-dependent synaptic
      processes that relate to the kinematics of whisking.

PMID- 17035541
TI  - Alpha-synuclein expression modulates microglial activation phenotype.
AB  - Recent Parkinson's disease research has focused on understanding the function of
      the cytosolic protein, alpha-synuclein, and its contribution to disease
      mechanisms. Within neurons, alpha-synuclein is hypothesized to have a role in
      regulating synaptic plasticity, vesicle release, and trafficking. In contrast,
      glial-expressed alpha-synuclein remains poorly described. Here, we examine the
      consequence of a loss of alpha-synuclein expression on microglial activation.
      Using a postnatal brain-derived culture system, we defined the phenotype of
      microglia from wild-type and knock-out alpha-synuclein mice (Scna-/-). Scna-/-
      microglia displayed a basally increased reactive phenotype compared with the wild
      type cells and an exacerbated reactive phenotype after stimulation. They also
      exhibited dramatic morphologic differences compared with wild-type, presenting as
      large, ramified cells filled with vacuole-like structures. This corresponded with
      increased protein levels of activation markers, CD68 and beta1 integrin, in the
      Scna-/- cells. More importantly, Scna-/- microglia, after stimulation, secreted
      elevated levels of proinflammatory cytokines, TNFalpha (tumor necrosis factor
      alpha) and IL-6 (interleukin-6), compared with wild type. However, despite the
      reactive phenotype, Scna-/- cells had impaired phagocytic ability. We demonstrate
      for the first time that alpha-synuclein plays a critical role in modulating
      microglial activation state. We suggest that altered microglial alpha-synuclein
      expression will affect their phenotype as has already been demonstrated in
      neurons. This has direct ramifications for the contribution of microglia to the
      pathophysiology of disease, particularly in familial cases linked to altered
      alpha-synuclein expression.

PMID- 17035542
TI  - Implications of assist-as-needed robotic step training after a complete spinal
      cord injury on intrinsic strategies of motor learning.
AB  - Robotic training paradigms that enforce a fixed kinematic control might be
      suboptimal for rehabilitative training because they abolish variability, an
      intrinsic property of neuromuscular control (Jezernik et al., 2003). In the
      present study we introduce "assist-as-needed" (AAN) robotic training paradigms
      for rehabilitation of spinal cord injury subjects. To test the efficacy of these
      robotic control strategies to teach spinal mice to step, we divided 27 adult
      female Swiss-Webster mice randomly into three groups. Each group was trained
      robotically by using one of three control strategies: a fixed training trajectory
      (Fixed group), an AAN training paradigm without interlimb coordination (Band
      group), and an AAN training paradigm with bilateral hindlimb coordination (Window
      group). Beginning at 14 d after a complete midthoracic spinal cord transection,
      the mice were trained daily (10 min/d, 5 d/week) to step on a treadmill 10 min
      after the administration of quipazine (0.5 mg/kg), a serotonin agonist, for a
      period of 6 weeks. During weekly performance evaluations, the mice trained with
      the AAN window paradigm generally showed the highest level of recovery as
      measured by the number, consistency, and periodicity of steps during the testing
      sessions. In all three measurements there were no significant differences between
      the Band and the Fixed training groups. These results indicate that the window
      training approach, which includes loose alternating interlimb coordination, is
      more effective than a fixed trajectory paradigm with rigid alternating interlimb
      coordination or an AAN paradigm without any interlimb constraints in promoting
      robust postinjury stepping behavior.

PMID- 17035543
TI  - Cerebellar modulation of trigeminal reflex blinks: interpositus neurons.
AB  - Because of its simplicity, blinking is a prominent model system in analysis of
      adaptation and conditioning with the cerebellum. Nevertheless, data on the role
      of the cerebellum in modulation of normal reflex blinks are limited. We
      correlated the discharge of interpositus (IP) neurons with normal trigeminal
      reflex blinks and blink adaptation in urethane-anesthetized rats. Two groups of
      IP neurons responded to cornea stimulation. One group, pause neurons, showed a
      long cessation of their tonic discharge beginning 6 ms before the end of lid
      closure. The second group, burst neurons, exhibited a transient increase in
      firing frequency at a constant interval after the cornea stimulus. The cessation
      of pause neuron activity appeared to contribute to the termination of blinks. The
      tonic discharge rate increased and the cessation of pause neuron activity was
      delayed coincident with increased amplitude and duration of reflex blinks
      produced by blink adaptation. There was a coincident increase in the amplitude
      and duration of reflex blinks with increased tonic activity and delayed pause in
      pause neurons treated with the GABA(A) antagonist, gabazine. Burst neurons did
      not appear to modulate reflex blinks. Burst neuron discharge correlated neither
      with blink characteristics normally nor with blink adaptation. These findings
      indicated that pause neurons affect reflex blinks by providing a tonic excitatory
      input to facial motoneurons during lid closure and then disfacilitating those
      motoneurons to adjust the termination of lid closure. Burst neurons may play a
      role in eyelid conditioning.

PMID- 17035544
TI  - Dopaminergic control of sleep-wake states.
AB  - Dopamine depletion is involved in the pathophysiology of Parkinson's disease,
      whereas hyperdopaminergia may play a fundamental role in generating
      endophenotypes associated with schizophrenia. Sleep disturbances are known to
      occur in both schizophrenia and Parkinson's disease, suggesting that dopamine
      plays a role in regulating the sleep-wake cycle. Here, we show that novelty
      exposed hyperdopaminergic mice enter a novel awake state characterized by
      spectral patterns of hippocampal local field potentials that resemble
      electrophysiological activity observed during rapid-eye-movement (REM) sleep.
      Treatment with haloperidol, a D2 dopamine receptor antagonist, reduces this
      abnormal intrusion of REM-like activity during wakefulness. Conversely, mice
      acutely depleted of dopamine enter a different novel awake state characterized by
      spectral patterns of hippocampal local field potentials that resemble
      electrophysiological activity observed during slow-wave sleep (SWS). This
      dopamine-depleted state is marked by an apparent suppression of SWS and a
      complete suppression of REM sleep. Treatment with D2 (but not D1) dopamine
      receptor agonists recovers REM sleep in these mice. Altogether, these results
      indicate that dopamine regulates the generation of sleep-wake states. We propose
      that psychosis and the sleep disturbances experienced by Parkinsonian patients
      result from dopamine-mediated disturbances of REM sleep.

PMID- 17035545
TI  - Ubiquitous and temperature-dependent neural plasticity in hibernators.
AB  - Hibernating mammals are remarkable for surviving near-freezing brain temperatures
      and near cessation of neural activity for a week or more at a time. This extreme
      physiological state is associated with dendritic and synaptic changes in
      hippocampal neurons. Here, we investigate whether these changes are a ubiquitous
      phenomenon throughout the brain that is driven by temperature. We
      iontophoretically injected Lucifer yellow into several types of neurons in fixed
      slices from hibernating ground squirrels. We analyzed neuronal microstructure
      from animals at several stages of torpor at two different ambient temperatures,
      and during the summer. We show that neuronal cell bodies, dendrites, and spines
      from several cell types in hibernating ground squirrels retract on entry into
      torpor, change little over the course of several days, and then regrow during the
      2 h return to euthermia. Similar structural changes take place in neurons from
      the hippocampus, cortex, and thalamus, suggesting a global phenomenon.
      Investigation of neural microstructure from groups of animals hibernating at
      different ambient temperatures revealed that there is a linear relationship
      between neural retraction and minimum body temperature. Despite significant
      temperature-dependent differences in extent of retraction during torpor, recovery
      reaches the same final values of cell body area, dendritic arbor complexity, and
      spine density. This study demonstrates large-scale and seemingly ubiquitous
      neural plasticity in the ground squirrel brain during torpor. It also defines a
      temperature-driven model of dramatic neural plasticity, which provides a unique
      opportunity to explore mechanisms of large-scale regrowth in adult mammals, and
      the effects of remodeling on learning and memory.

PMID- 17035546
TI  - Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of
      secretory granules.
AB  - Alpha-neurexins constitute a family of neuronal cell surface molecules that are
      essential for efficient neurotransmission, because mice lacking two or all three
      alpha-neurexin genes show a severe reduction of synaptic release. Although
      analyses of alpha-neurexin knock-outs and transgenic rescue animals suggested an
      involvement of voltage-dependent Ca2+ channels, it remained unclear whether alpha
      neurexins have a general role in Ca2+-dependent exocytosis and how they may
      affect Ca2+ channels. Here we show by membrane capacitance measurements from
      melanotrophs in acute pituitary gland slices that release from endocrine cells is
      diminished by >50% in adult alpha-neurexin double knock-out and newborn triple
      knock-out mice. There is a reduction of the cell volume in mutant melanotrophs;
      however, no ultrastructural changes in size or intracellular distribution of the
      secretory granules were observed. Recordings of Ca2+ currents from melanotrophs,
      transfected human embryonic kidney cells, and brainstem neurons reveal that alpha
      neurexins do not affect the activation or inactivation properties of Ca2+
      channels directly but may be responsible for coupling them to release-ready
      vesicles and metabotropic receptors. Our data support a general and essential
      role for alpha-neurexins in Ca2+-triggered exocytosis that is similarly important
      for secretion from neurons and endocrine cells.

PMID- 17035547
TI  - An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in
      a mouse model of neurodegenerative disease.
AB  - Various studies suggest that proteolytic activity may be involved in a number of
      neurodegenerative disorders, including stroke and seizure. In this report, we
      examined the role of tryptic serine proteases, plasminogen activators (PAs), in
      the evolution of a neurodegenerative disease. Transgenic mice overexpressing an
      axonally secreted inhibitor of serine proteases (neuroserpin) were crossed with
      mice characterized by a "dying-back" motor neuron disease [progressive motor
      neuronopathy (pmn/pmn)]. Compared with pmn/pmn mice that showed an increase in PA
      activity, double mutant mice had decreased PA activity in sciatic nerves and
      spinal cord; their lifespan was increased by 50%, their motor behavior was
      stabilized, and histological analysis revealed increased numbers of myelinated
      axons and rescue of motoneuron number and size. This is the first report showing
      that a class of serine proteases (PAs) may be involved in the pathogenesis of a
      motor neuron disease and more specifically in axonal degeneration. Inhibiting
      serine proteases could offer a new strategy for delaying these disorders.

PMID- 17035548
TI  - Effects of transdermal testosterone application on the ovarian response to FSH in
      poor responders undergoing assisted reproduction technique-a prospective,
      randomized, double-blind study.

PMID- 17035549
TI  - Development of a novel home sperm test - temperature range.

PMID- 17035550
TI  - Development of a novel home sperm test - what are the limitations?

PMID- 17035551
TI  - Remembering and appreciating Wayne S. Fenton.

PMID- 17035552
TI  - Law & psychiatry: insanity, guilty minds, and psychiatric testimony.
AB  - This column describes a recent Supreme Court case, Clark v. Arizona, in which an
      adolescent who had schizophrenia was convicted of first-degree murder of a police
      officer who he believed was a hostile space alien. The Arizona courts had
      rejected his insanity defense as well as a second defense that he lacked the
      required intent to commit the crime (mens rea) because his delusions interfered
      with his knowing that the victim was a police officer. The Court ultimately
      declined to overturn Arizona's rules regarding the insanity defense and mens rea.
      However, the column highlights the points in Justice Souter's decision that may
      have implications for any case involving mental health issues.

PMID- 17035553
TI  - Innovations: child and adolescent psychiatry: measuring outcomes of real-world
      youth psychotherapy: whom to ask and what to ask?
AB  - To illustrate complexities in outcomes measurement for youths receiving community
      based mental health services, this column presents data on 112 youths in publicly
      funded, usual-care psychotherapy. Youths and their parents separately completed
      standard measures of outcomes in three domains--symptoms, functioning, and family
      environment--at baseline and at six months. The results indicate minimal
      agreement between youths and parents on individual outcome domains and almost no
      overlap for each informant (youth and parent) across multiple domains. These
      findings are especially relevant because service providers are increasingly
      required to demonstrate treatment effectiveness and monitor youths' progress. The
      results highlight the complexities in measuring the impact of care and indicate
      the need to develop more feasible methods to measure multidimensional outcomes.

PMID- 17035554
TI  - Best practices: environmental and therapeutic issues in psychiatric hospital
      design: toward best practices.
AB  - The psychiatric hospital environment plays a significant, though often
      underappreciated, role in patient and staff functioning. This column reviews the
      literature on important environmental and therapeutic issues in psychiatric
      hospital design. Research findings and clinical conjecture reported over the past
      50 years indicate that intervening environmentally through clinically informed,
      patient-centered design can improve functioning both among and between patients
      and staff. This column identifies specific best practice considerations and
      recommendations for designing inpatient psychiatric facilities and may serve as a
      useful planning resource to those interested in adopting a patient-centered,
      inclusive approach to design and treatment.

PMID- 17035555
TI  - Personal accounts: lawyering, psychiatric treatment, and schizophrenia: a healing
      interaction.

PMID- 17035556
TI  - Employment barriers for persons with psychiatric disabilities: update of a report
      for the President's Commission.
AB  - A major public policy problem is the extremely low labor force participation of
      people with severe mental illness coupled with their overrepresentation on the
      public disability rolls. This situation is especially troubling given the
      existence of evidence-based practices designed to return them to the labor force.
      This article reviews research from the fields of disability, economics, health
      care, and labor studies to describe the nature of barriers to paid work and
      economic security for people with disabling mental disorders. These barriers
      include low educational attainment, unfavorable labor market dynamics, low
      productivity, lack of appropriate vocational and clinical services, labor force
      discrimination, failure of protective legislation, work disincentives caused by
      state and federal policies, poverty-level income, linkage of health care access
      to disability beneficiary status, and ineffective work incentive programs. The
      article concludes with a discussion of current policy initiatives in health care,
      mental health, and disability. Recommendations for a comprehensive system of
      services and supports to address multiple barriers are presented. These include
      access to affordable health care, including mental health treatment and
      prescription drug coverage; integrated clinical and vocational services; safe and
      stable housing that is not threatened by changes in earned income; remedial and
      postsecondary education and vocational training; benefits counseling and
      financial literacy education; economic security through asset development; legal
      aid for dealing with employment discrimination; peer support and self-help to
      enhance vocational self-image and encourage labor force attachment; and active
      involvement of U.S. business and employer communities.

PMID- 17035558
TI  - A comparison of competitive employment outcomes for the clubhouse and PACT
      models.
AB  - OBJECTIVE: This study determined whether the clubhouse model of community support
      and psychiatric rehabilitation can produce competitive employment outcomes that
      are comparable or superior to those of the Program of Assertive Community
      Treatment (PACT) model. METHODS: This longitudinal study followed a group of 170
      individuals with severe mental illness who were randomly assigned either to the
      experimental design, a clubhouse program (N=86), or to the control design, a PACT
      team (N=84). Study participants were tracked for 30 months, and employment
      outcome data were collected. RESULTS: After 30 months, 72 clubhouse and 76 PACT
      participants remained active in the project. After 30 months, 74 percent of PACT
      participants and 60 percent of clubhouse participants had been placed in at least
      one job. The average clubhouse participant worked 21.8 weeks per job and earned
      $7.38 per hour, whereas the average PACT participant worked 13.1 weeks per job
      and earned $6.30 per hour. CONCLUSIONS: Participants from both the PACT and
      clubhouse models achieved high employment levels, with no significant differences
      in weekly employment or 30-month job placement rates over the course of the
      study. During this time, clubhouse participants earned significantly higher wages
      and remained competitively employed for significantly more weeks per job than
      PACT participants.

PMID- 17035559
TI  - Strategies for coping with cognitive impairments of clients in supported
      employment.
AB  - OBJECTIVE: This study evaluated the strategies used by employment specialists to
      help clients in supported employment programs manage cognitive impairments that
      interfered with obtaining and keeping jobs. METHODS: Twenty-five supported
      employment specialists were surveyed to identify strategies they used to help
      their clients cope with cognitive problems in the domains of attention,
      psychomotor speed, memory, and problem solving. Then, 50 employment specialists
      were surveyed to determine whether they used each of the different coping
      strategies generated in the first part of the study. For each strategy used, they
      rated how effective it was. RESULTS: Employment specialists reported using a
      total of 76 different strategies for helping their clients cope with cognitive
      difficulties. The specialists reported using an average of 48 different coping
      strategies, which they rated on average as just below effective. Strategies for
      dealing with attention problems were rated as more effective than strategies used
      in the other three domains. The number of coping strategies that they reported
      using was significantly correlated with the perceived effectiveness of the
      strategies and the proportion of clients in their caseload who were working.
      CONCLUSIONS: Supported employment specialists were actively involved in helping
      clients cope with their cognitive impairments. Use of more strategies was
      correlated with specialists' greater perceived effectiveness of the strategies
      and with higher rates of working clients on their caseloads, although the reasons
      for these associations are unclear. Further research is needed to evaluate
      whether employment specialists' use of more strategies to help clients cope with
      cognitive problems contributes to better work outcomes.

PMID- 17035557
TI  - Supported employment outcomes of a randomized controlled trial of ACT and
      clubhouse models.
AB  - OBJECTIVE: In a randomized controlled trial, a vocationally integrated program of
      assertive community treatment (ACT) was compared with a certified clubhouse in
      the delivery of supported employment services. METHODS: Employment rates, total
      work hours, and earnings for 121 adults with serious mental illness interested in
      work were compared with published benchmark figures for exemplary supported
      employment programs. The two programs were then compared on service engagement,
      retention, and employment outcomes in regression analyses that controlled for
      background characteristics, program preference, and vocational service receipt.
      RESULTS: Outcomes for 63 ACT and 58 clubhouse participants met or exceeded most
      published outcomes for specialized supported employment teams. Compared with the
      clubhouse program, the ACT program had significantly (p<.05) better service
      engagement (ACT, 98 percent; clubhouse, 74 percent) and retention (ACT, 79
      percent; clubhouse, 58 percent) over 24 months, but there was no significant
      difference in employment rates (ACT, 64 percent; clubhouse, 47 percent). Compared
      with ACT participants, clubhouse participants worked significantly longer (median
      of 199 days versus 98 days) for more total hours (median of 494 hours versus 234
      hours) and earned more (median of $3,456 versus $1,252 total earnings). Better
      work performance by clubhouse participants was partially attributable to higher
      pay. CONCLUSIONS: Vocationally integrated ACT and certified clubhouses can
      achieve employment outcomes similar to those of exemplary supported employment
      teams. Certified clubhouses can effectively provide supported employment along
      with other rehabilitative services, and the ACT program can ensure continuous
      integration of supported employment with clinical care.

PMID- 17035560
TI  - Increasing the utilization of supported employment services with the need for
      change scale.
AB  - OBJECTIVE: This study compared consumers' self-reports of felt need for
      employment with their practitioners' assessments of need to determine whether
      consumers' decisions to attend supported employment services and their acceptance
      into supported employment services could be predicted. METHODS: In 2004 a group
      of 147 unemployed service recipients from a region of the Connecticut Department
      of Mental Health and Addiction Services rated their felt need for employment on
      the Need for Change (NFC) scale. Correlations between felt need and their
      decisions to accept supported employment services within the next six months were
      determined. Correlations between their practitioners' independent decisions to
      refer them to supported employment services and the consumers' decisions to
      accept referrals were also determined. RESULTS: The consumers' decisions to
      accept a referral had a correlation of .72 with their NFC ratings, compared with
      .17 with their practitioners' decision to refer them. Of 49 people with high NFC
      ratings (high felt need for employment), 45 were accepted into supported
      employment services. Only ten of these consumers would have been referred by
      their practitioners. The NFC increased referrals to supported employment by 24
      percent in this sample. CONCLUSION: The NFC scale may be a valid tool for
      referring consumers to supported employment services.

PMID- 17035562
TI  - Commentary: policy priorities and shifting sands in the supported employment
      evidence base.

PMID- 17035561
TI  - Rates of unemployment and incidence of police-initiated examinations for
      involuntary hospitalization in Florida.
AB  - OBJECTIVE: This study tested the hypothesis that contraction of regional
      economies affects the incidence of involuntary admissions to psychiatric
      emergency services by reducing community tolerance for persons perceived as
      threatening to others. METHODS: This hypothesis was tested with time-series
      analyses of the relationship between initial claims for unemployment in Florida
      between July 4, 1999, and June 28, 2003, and the weekly number of men and women
      presented by police to be examined for involuntary psychiatric hospitalization
      because of danger to others. The analyses controlled for admissions presented by
      mental health professionals because of danger to others and for admissions
      presented by police because of neglect or disability. RESULTS: When the analyses
      controlled for autocorrelation and other covariates, claims for unemployment
      insurance were significantly associated with the number of men presented by
      police for danger to others. During the study period, police presented 5,897 men
      for examination because of danger to others. Increased unemployment claims were
      associated with approximately 309 more men being presented for examination than
      expected from prior presentation rates and from the number presented by mental
      health professionals for danger to others and by police for neglect or
      disability. No such association was found for women. CONCLUSIONS: Consistent with
      theory, this study found that presentations for involuntary admission to
      psychiatric services increased after contractions in the labor market. Combining
      the methods of this study with econometric forecasting may allow providers to
      anticipate better the need for psychiatric services.

PMID- 17035563
TI  - Randomized trial of a telephone care management program for outpatients starting
      antidepressant treatment.
AB  - OBJECTIVE: This study evaluated the effectiveness of a structured telephone-based
      care management program for patients in a prepaid health plan receiving new
      antidepressant prescriptions from psychiatrists. METHODS: Potential participants
      were identified with computerized medical records and contacted by telephone.
      Eligible and consenting participants were randomly assigned to continued usual
      care (N=104) or to a three-session telephone care management program (N=103).
      Care management contacts included assessment of depressive symptoms, medication
      adherence, and medication side effects with structured feedback to treating
      psychiatrists. Effectiveness was assessed three and six months after
      randomization by blinded telephone assessments (depression scale on the Hopkins
      Symptom Checklist [SCL] and patient-rated global improvement). Computerized
      records were used to assess medication adherence and frequency of in-person
      follow-up visits. RESULTS: Compared with usual care, the care management
      intervention had no significant effect on the mean score of the SCL depression
      scale at six months, on the probability of 50 percent improvement in depressive
      symptoms (41 percent for care management and 37 percent for usual care), or on
      the probability of patient-rated improvement (57 percent for care management and
      52 percent for usual care). Patients assigned to care management made
      significantly more medication management visits over six months (2.4 visits
      compared with 2.0 visits; p=.035), but there were no significant differences in
      rates of adequate medication treatment. CONCLUSIONS: This study found that a low
      intensity telephone care management program did not appear to significantly
      improve clinical outcomes for patients starting antidepressant treatment.
      Compared with findings from earlier primary care studies, this study found that
      patients receiving care from a psychiatrist received more intensive treatment,
      although many still experienced poor outcomes.

PMID- 17035564
TI  - Depression outcomes and quality of postdischarge care of elders hospitalized for
      major depression.
AB  - OBJECTIVES: Elders with depression are disproportionately hospitalized, and they
      depend on postacute care for recovery. The authors hypothesized that higher
      quality of postacute care would be associated with better depression outcomes for
      older adults six months after discharge for inpatient psychiatric care. The study
      also explored the time frame in which effects of quality of care on depression
      outcomes were manifested. METHODS: The sample consisted of 148 elders (ages 60-95
      years) who were hospitalized for major depression and discharged to their homes.
      Quality of care was measured by the extent to which services met patients' needs.
      Specifically, quality of care was assessed by whether four domains of needs
      (psychiatric, medical, functional, and psychosocial) were met six weeks and six
      months postdischarge. Depression outcomes at six months were measured by the
      Geriatric Depression Scale. RESULTS: In bivariate analyses at six weeks, no
      quality-of-care variables were associated with depression outcomes, but in
      bivariate analyses at six months, quality of functional and psychosocial care was
      related to depression outcomes. Multivariate analyses revealed that those whose
      psychosocial needs were unmet at six months showed worse depression outcomes.
      CONCLUSIONS: Findings provided partial support for the association between
      quality of care and depression outcomes, in that quality of psychosocial care was
      associated with better outcomes. Also, the findings suggest that the relationship
      between quality of psychosocial care and depression outcomes may be evident after
      six months of postacute care.

PMID- 17035565
TI  - Reliability and validity of the substance abuse outcomes module.
AB  - OBJECTIVE: The study sought to determine the validity and reliability of the
      Substance Abuse Outcomes Module (SAOM), a self-report tool designed to assess
      patient characteristics, process of care, and outcomes of care, using a minimum
      amount of information, in order to improve treatment. METHODS: A longitudinal
      field test (baseline and three-month follow-up) compared the SAOM to seven other
      research instruments in the assessment of 100 substance-abusing patients who were
      entering a new treatment episode. Quota samples of patients were drawn from two
      private inpatient substance abuse treatment facilities and an outpatient
      methadone clinic. The study's primary outcome measures were diagnostic accuracy,
      internal and test-retest reliability of key constructs, concurrent and predictive
      validity, and sensitivity to change. Cronbach's alpha coefficients were
      calculated to examine internal consistency and reliability. Intraclass
      correlation coefficients and kappa coefficients were used to examine test-retest
      reliability. Concurrent validity of outcomes measures was examined with Pearson
      or Spearman correlation coefficients and chi square and kappa statistics. Changes
      between baseline and follow-up were examined as a function of case-mix measures
      with ordinary least-squares multiple regression. Sensitivity to change was
      examined by calculating effect size scores. RESULTS: The SAOM had high internal
      consistency and a high level of agreement with research diagnoses at baseline and
      follow-up. The SAOM was found to be highly reliable, to have very strong
      validity, and to be sensitive to clinical change. CONCLUSIONS: The SAOM appears
      to be a reasonably reliable and valid self-report instrument when used to monitor
      substance abuse treatment among patients with a primary substance use diagnosis.

PMID- 17035566
TI  - Statistical benchmarks for process measures of quality of care for mental and
      substance use disorders.
AB  - OBJECTIVE: Benchmarks, representing the level of performance achieved by the best
      performing providers, can be used to set achievable goals for improving care, but
      they have not heretofore been available for mental health care. This article
      describes the application of a method for developing statistical benchmarks for
      12 process measures of quality of care for mental and substance use disorders.
      METHODS: Twelve quality measures--taken from a core measure set selected by a
      multistakeholder panel through a formal consensus process--were constructed from
      1994-1995 administrative data on care received by Medicaid beneficiaries in six
      states. Conformance rates were calculated at the provider level and presented as
      means, 90th-percentile results, and statistical benchmarks. Sample sizes for each
      measure ranged from 356 to 4,494 providers and from 1,205 to 78,627 cases. Three
      measures involved antidepressant treatment, two involved antipsychotic treatment,
      and one involved mood stabilizers for bipolar disorder. Six other measures
      involved follow-up treatment visits. RESULTS: Benchmarks for provider-level
      performance ranged from 59.7 percent to 97.7 percent, markedly higher than the
      mean results, which ranged from 9.4 percent to 65.4 percent. Benchmark results
      varied widely-in contrast to results for these measures at the 90th percentile of
      providers and in contrast to performance standards that apply the same numerical
      goal across varied clinical processes. CONCLUSIONS: Statistical benchmarks can be
      applied to results from quality assessment of mental health care. Further
      research should examine whether incorporating benchmarks into quality improvement
      activities leads to better mental health care and substance-related care and
      improved outcomes.

PMID- 17035567
TI  - Diagnosing psychotic disorders in the emergency department in the context of
      substance use.
AB  - OBJECTIVE: For patients who are actively using a substance and experience
      psychotic symptoms, determining whether the psychotic symptoms are due to a
      primary psychotic disorder or are substance induced is challenging, especially in
      emergency departments, where historical information is limited. This study
      examined the accuracy and subsequent treatment implications of emergency
      department diagnoses among substance-using patients who were having their first
      psychotic episode. METHODS: Emergency department diagnoses for 302 patients were
      compared with best-estimate longitudinal diagnoses (BELDs) based on research
      assessments at three time points (baseline, six months, and 12 months). RESULTS:
      Of the 223 patients whose symptoms were diagnosed in the emergency department as
      a primary psychotic disorder, one-quarter were determined by the BELD to have
      substance-induced psychosis or no psychosis. Overall, the diagnostic agreement
      was only fair (kappa=.32). Patients with an emergency department diagnosis of
      primary psychosis were significantly more likely than those with an emergency
      department diagnosis of substance-induced psychosis to be hospitalized, started
      on antipsychotic medication, and referred to mental health services instead of
      treatment for substance use (p<.001). Patients given an emergency department
      diagnosis of primary psychosis who were found by the BELD to have substance
      induced psychosis or no psychosis were significantly more likely to be treated
      for a psychotic disorder rather than for substance-induced psychosis (p<.001)
      CONCLUSIONS: Clinicians in psychiatric emergency departments appear to have a
      tendency to attribute psychotic symptoms to a primary psychotic disorder rather
      than to concurrent substance use. Given that the diagnosis has significant
      implications for future management, it is important to improve diagnostic
      approaches in the emergency department.

PMID- 17035568
TI  - Mortality among discharged psychiatric patients in Florence, Italy.
AB  - OBJECTIVE: Psychiatric disorders involve an increased risk of mortality. In Italy
      psychiatric services are community based, and hospitalization is mostly reserved
      for patients with acute illness. This study examined mortality risk in a cohort
      of psychiatric inpatients for 16 years after hospital discharge to assess the
      association of excess mortality from natural or unnatural causes with clinical
      and sociodemographic variables and time from first admission. METHODS: At the end
      of 2002 mortality and cause of death were determined for all patients (N=845) who
      were admitted during 1987 to the eight psychiatric units active in Florence. The
      mortality risk of psychiatric patients was compared with that of the general
      population of the region of Tuscany by calculating standardized mortality ratios
      (SMRs). Poisson multivariate analyses of the observed-to-expected ratio for
      natural and unnatural deaths were conducted. RESULTS: The SMR for the sample of
      psychiatric patients was threefold higher than that for the general population
      (SMR=3.0; 95 percent confidence interval [CI]=2.7-3.4). Individuals younger than
      45 years were at higher risk (SMR=11.0; 95 percent CI 8.0-14.9). The SMR for
      deaths from natural causes was 2.6 (95 percent CI=2.3-2.9), and for deaths from
      unnatural causes it was 13.0 (95 percent CI=10.1-13.6). For deaths from unnatural
      causes, the mortality excess was primarily limited to the first years after the
      first admission. For deaths from natural causes, excess mortality was more stable
      during the follow-up period. CONCLUSIONS: Prevention of deaths from unnatural
      causes among psychiatric patients may require promotion of earlier follow-up
      after discharge. Improving prevention and treatment of somatic diseases of
      psychiatric patients is important to reduce excess mortality from natural causes.

PMID- 17035569
TI  - Mortality and medical comorbidity among patients with serious mental illness.
AB  - OBJECTIVES: This study examined mortality and medical comorbidity among patients
      with serious mental illness in Ohio. METHODS: Data for 20,018 patients admitted
      to an Ohio public mental health hospital between 1998 and 2002 were matched
      against state death records, and 608 deaths were identified. Leading causes of
      death and medical comorbidities, years of potential life lost (YPLL), and
      standardized mortality ratios were calculated for this population. RESULTS: Heart
      disease (126 persons, or 21 percent) and suicides (108 persons, or 18 percent)
      were the leading causes of death. The mean+/-SD number of YPLL was 32.0+/-12.6
      years. The highest cause-specific mean YPLL was for suicides (41.7+/-10.3 years).
      Deaths from unnatural causes had higher mean YPLL than deaths from any other
      causes. Cause-specific mean YPLL were higher for women than for men, except for
      homicides, pneumonia and influenza, and heart disease. The aggregated
      standardized mortality ratio from all causes of death was 3.2, corresponding to
      417 excess deaths (p<.001). Obesity (144 persons, or 24 percent) and hypertension
      (136 persons, or 22 percent) were the most prevalent medical comorbidities.
      CONCLUSIONS: This study demonstrated excess mortality among patients in Ohio with
      serious mental illness. Results highlight the need to integrate delivery of
      currently fragmented mental and physical health services and to target
      interventions that improve quality-of-life outcomes for this population.

PMID- 17035570
TI  - An update on affirmative businesses or social firms for people with mental
      illness.
AB  - Social firms, or "affirmative businesses" as they are known in North America, are
      businesses created to employ people with disabilities and to provide a needed
      product or service. This Open Forum offers an overview of the development and
      status of social firms. The model was developed in Italy in the 1970s for people
      with psychiatric disabilities and has gained prominence in Europe. Principles
      include that over a third of employees are people with a disability or labor
      market disadvantage, every worker is paid a fair-market wage, and the business
      operates without subsidy. Independent of European influence, affirmative
      businesses also have developed in Canada, the United States, Japan, and
      elsewhere. The success of individual social firms is enhanced by locating the
      right market niche, selecting labor-intensive products, having a public
      orientation for the business, and having links with treatment services. The
      growth of the social firm movement is aided by legislation that supports the
      businesses, policies that favor employment of people with disabilities, and
      support entities that facilitate technology transfer. Social firms can empower
      individual employees, foster a sense of community in the workplace, and enhance
      worker commitment through the organization's social mission.

PMID- 17035571
TI  - Impact of consumer-operated services on empowerment and recovery of people with
      psychiatric disabilities.
AB  - OBJECTIVE: Although the professional literature is replete with descriptions of
      consumer-operated services, empirical examination of these services has been
      relatively limited. In this study, the cross-sectional relationship between
      participation in consumer-operated services and measures of recovery and
      empowerment is examined. METHODS: A total of 1,824 people with psychiatric
      disability indicated whether they had participated in a peer support program (the
      proxy of consumer-operated services) during the past four months. They also were
      administered two five-factor measures of recovery and of empowerment. RESULTS:
      Participation in peer support was associated with nine of ten factors generated
      by the recovery and empowerment instruments. These associations remained
      significant when commensurate demographic variables were controlled for.
      CONCLUSIONS: Participation in peer support showed a significant association with
      multiple outcome and recovery subscales, but the magnitude of the effect was
      small. The associative nature of the data precludes stating that peer support
      caused the observed improvement.

PMID- 17035572
TI  - Effectiveness of a collaborative recovery training program in Australia in
      promoting positive views about recovery.
AB  - OBJECTIVE: This study examined the impact of a two-day, recovery-based training
      program for mental health workers on knowledge, attitudes, and hopefulness
      related to the recovery prospects of people with enduring mental illness.
      METHODS: A self-report pre-post training repeated-measures design was used with
      248 mental health workers from the community-based government health sector
      (N=147) and nongovernment organizations (N= 101) in eastern Australia. RESULTS:
      Staff attitudes and hopefulness improved after training. Trainees significantly
      increased their knowledge regarding principles of recovery and belief in the
      effectiveness of collaboration and consumer autonomy support, motivation
      enhancement, needs assessment, goal striving, and homework use. CONCLUSIONS: This
      preliminary evidence indicates that staff recovery orientation can improve with
      minimal training.

PMID- 17035573
TI  - State psychiatric hospital census after the 1999 Olmstead Decision: evidence of
      decelerating deinstitutionalization.
AB  - OBJECTIVE: The Supreme Court ruled in the 1999 Olmstead decision that
      "unjustified isolation" of individuals with disabilities in institutions is a
      violation of the Americans With Disabilities Act. This study examined the extent
      to which state psychiatric hospital census across the United States has changed
      significantly post-Olmstead. METHODS: Twenty years of national state hospital
      census data (1984-2003) were used to assess trends in the rate of declines from
      pre- to post-Olmstead periods. Data were organized into five four-year periods.
      RESULTS: Steady declines in the hospital census nationally were found over all
      periods, with especially large decreases in the 1990s. However, when the percent
      change in hospital census in the two periods immediately before the Olmstead
      decision (between 1992-1995 and 1996-1999) were compared with the percent change
      in the periods immediately before and immediately after the Olmstead decision
      (between 1996-1999 and 2000-2003), an 8 percent decrease in the magnitude of
      decline was seen. CONCLUSIONS: State hospital census continues to decline but has
      slowed significantly during the post-Olmstead period. More study of the factors
      associated with this decline is needed.

PMID- 17035574
TI  - Gender- and trauma-related predictors of use of mental health treatment services
      among primary care patients.
AB  - OBJECTIVE: Use of mental health care was investigated as a function of gender,
      traumatic event frequency, posttraumatic stress disorder (PTSD), and attitudes
      toward treatment among 194 primary care patients. METHODS: Patients were
      recruited from primary care clinics, administered the Stressful Life Events
      Screening Questionnaire, PTSD Symptom Scale, Attitudes Toward Seeking
      Professional Psychological Help-Short Form, and a survey on use of services.
      RESULTS: Lifetime mental health treatment was related to increased frequency of
      traumatic events, positive attitudes toward treatment, and probable PTSD. Recent
      use of mental health care and intensity of use were related to female gender and
      greater frequency of trauma. Regression models yielded significant associations
      for trauma frequency, positive treatment attitudes, and female gender. Trauma and
      PTSD were associated with use more than gender and treatment attitudes were.
      CONCLUSIONS: Use of and adherence to treatment may be improved by targeting
      attitudes toward treatment.

PMID- 17035576
TI  - Recovery-oriented care.

PMID- 17035577
TI  - Malignant criminalization: from hypothesis to theory.

PMID- 17035578
TI  - Community reintegration of prisoners with mental illness.

PMID- 17035582
TI  - "Antipsychiatry" and "consumerism": perspectives and definitions.

PMID- 17035584
TI  - The cost of low-demand housing programs.

PMID- 17035585
TI  - Multiple sclerosis, mental illness, and forced treatment.

PMID- 17035586
TI  - Legal consequences of seclusion and restraint.

PMID- 17035588
TI  - MS does not damage the brain; serious mental illnesses do.

PMID- 17035589
TI  - Successful use of VNS for depression.

PMID- 17035590
TI  - Imagining the ecotrienes: a helpful new class of peptides.

PMID- 17035591
TI  - Psychiatric effects of heat waves.

PMID- 17035592
TI  - Providing jail diversion for people with mental illness.

PMID- 17035593
TI  - Pursuing perfect depression care.

PMID- 17035594
TI  - Providing recovery-based treatment to enhance quality of life.

PMID- 17035595
TI  - Cellular retinoic acid bioavailability determines epithelial integrity: Role of
      retinoic acid receptor alpha agonists in colitis.
AB  - The epithelial barrier is determined primarily by intercellular tight junctions
      (TJs). We have demonstrated previously that all-trans retinoic acid (atRA) plays
      an important role in forming functional TJs through a specific retinoic acid
      receptor (RAR)/retinoid X receptor heterodimer in epithelial cells. However, the
      physiological relevance of retinoic acids (RAs) in maintaining the epithelial
      integrity remains to be examined. Here, we show that several types of RA,
      including atRA, promote the barrier function of epithelial TJs. Conversely, RA
      depletion in the cells by overexpressing CYP26s, cytochrome P450 enzymes
      specifically involved in the metabolic inactivation of RAs, induces an increase
      of permeability as measured by two differently sized tracer molecules, inulin and
      mannitol. This RA-mediated enhancement of barrier function is potentially
      associated with the increased expression of TJ-associated genes such as occludin,
      claudin-1, claudin-4, and zonula occludens-1. We also found that RARalpha is a
      preferential regulator of the epithelial barrier in vitro. Studies of murine
      experimental colitis, which is characterized by increased gut permeability,
      reveal that RARalpha stimulation significantly attenuates the loss of the
      epithelial barrier during colitis in vivo. Our results suggest that cellular RA
      bioavailability determines the epithelial integrity, because it is a critical
      regulator for barrier protection during mucosal injuries.

PMID- 17035596
TI  - Estrogen receptor antagonist fulvestrant (ICI 182,780) inhibits the anti
      inflammatory effect of glucocorticoids.
AB  - The glucocorticoid receptor (GR) and estrogen receptor (ER) play important roles
      in both physiological and pathological conditions involving cell growth and
      differentiation, lipolysis, control of glucose metabolism, immunity, and
      inflammation. In fact, recent studies suggest that 17beta-estradiol, like
      glucocorticoids, may also have anti-inflammatory properties, even if the
      molecular mechanisms responsible for these activities have not yet been
      completely clarified. The present study was designed to gain a better
      understanding of the possible cross-talk between GR and ER in a model of lung
      inflammation (carrageenan-induced pleurisy). In particular, we have investigated
      whether fulvestrant (ICI 182,780), a selective ER-alpha antagonist, is able to
      attenuate the well known anti-inflammatory effect of dexamethasone (DEX), a
      synthetic glucocorticoid, in ovariectomized rats. We show that ICI 182,780, a
      selective ER-alpha antagonist, reverses the anti-inflammatory activity exhibited
      by DEX. Moreover, the coadministration of ICI 182,780 significantly inhibited the
      ability of DEX to reduce: 1) the degree of lung injury, 2) the rise in
      myeloperoxidase activity, 3) the increase of poly-(ADP-ribose) polymerase
      activity, tumor necrosis factor alpha, and interleukin-1beta levels, 4) inducible
      nitric-oxide synthase, 5) lipid peroxidation, 6) nitrotyrosine formation, 7)
      cyclooxygenase expression, and 8) the IkappaB-alpha degradation caused by
      carrageenan administration. In addition, quantitative PCR shows that DEX down
      regulates GR and up-regulates glucocorticoid-induced leucine zipper levels,
      whereas ICI 182,780 does not counteract these effects. In conclusion, these
      results suggest that the in vivo anti-inflammatory property of DEX is also
      related to the ER-alpha.

PMID- 17035597
TI  - Down-regulation of inhibitor of apoptosis proteins by deguelin selectively
      induces apoptosis in breast cancer cells.
AB  - The identification of differentially regulated apoptotic signals in normal and
      tumor cells allows the development of cancer cell-selective therapies. Increasing
      evidence shows that the inhibitor of apoptosis (IAP) proteins survivin and XIAP
      are highly expressed in tumor cells but are absent or have very low levels of
      expression in normal adult tissues. We found that inhibiting AKT activity with 10
      to 100 nM deguelin, a small molecule derived from natural products, markedly
      reduced the levels of both survivin and XIAP, inducing apoptosis in human breast
      cancer cells but not in normal cells. It is noteworthy that we detected an
      elevated level of cleaved poly(ADP-ribose) polymerase, a signature of caspase
      activation, without a significant increase in caspase activity in deguelin
      treated cancer cells. Our results suggest that severe down-regulation of the IAPs
      by deguelin releases their inhibitory activity over pre-existing active caspases
      present in cancer cells, inducing apoptosis without the need for further caspase
      activation. Because normal cells have very low levels of p-AKT, XIAP, survivin,
      and pre-existing caspase activity, deguelin had little effect on those cells. In
      addition, we found that combining deguelin with chemotherapy drugs enhanced drug
      induced apoptosis selectively in human tumor cells, which suggests that deguelin
      has great potential for chemosensitization and could represent a new therapeutic
      agent for treatment of breast cancer.

PMID- 17035599
TI  - An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in
      human liver microsomes.
AB  - The human cytochrome P450 (P450) system is implicated in many drug interactions.
      Lisdexamfetamine dimesylate (NRP104), the proposed generic name for a new agent
      under investigation for treatment of attention deficit hyperactivity disorder,
      was recently analyzed for inhibitory drug-drug interactions with seven major P450
      isoforms using pooled human liver microsomes. Probe substrates were used near the
      K(m) concentration values reported in the literature for CYP1A2 (phenacetin),
      CYP2A6 (coumarin), CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2C19 ([S]
      mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam and testosterone),
      and lisdexamfetamine was evaluated at concentrations ranging from 0.01 to 100 muM
      for its ability to inhibit the activity of these seven P450 isoforms. NADPH was
      added to one set of samples to initiate metabolic reactions, which were then
      terminated by adding organic solvent, vortexing the samples, and placing them on
      ice. The relevant substrates were then introduced to both sets of samples so that
      the percentage of remaining activity could be measured and compared. In addition,
      these samples were compared with other samples with the same concentrations of
      lisdexamfetamine but without preincubation. None of the seven P450 isoforms
      showed any concentration-dependent inhibition. Comparison of results from
      microsomes preincubated with and without NADPH showed no mechanism-based
      inhibition. Neither concentration-dependent nor mechanism-based inhibition caused
      by time-dependent inactivation of human P450 isoforms was shown for
      lisdexamfetamine during in vitro testing. The evidence suggests that
      lisdexamfetamine has a low potential for drug-drug interactions or initiation of
      drug-drug interactions.

PMID- 17035598
TI  - A new CYP3A5 variant, CYP3A5*11, is shown to be defective in nifedipine
      metabolism in a recombinant cDNA expression system.
AB  - A new CYP3A5 variant, CYP3A5*11, was found in a white European subject by DNA
      sequencing. The CYP3A5*11 allele contains a single nucleotide polymorphism (SNP)
      (g.3775A>G) in exon 2, which results in a Tyr53Cys substitution, and a g.6986A>G
      splice change, the latter SNP previously reported in the defective CYP3A5*3
      allele. However, the CYP3A5*3 is not a null allele because this variant is
      associated with leaky splicing, resulting in small amounts of functional protein
      still being produced. Therefore, we constructed a cDNA coding for the newly
      identified CYP3A5.11 protein by site-directed mutagenesis, expressed it in
      Escherichia coli, and partially purified it. Whereas bacteria transformed with
      wild-type CYP3A5*1 cDNA expressed predominantly cytochrome P450 (P450), those
      transfected with CYP3A5*11 expressed a significant amount of denatured cytochrome
      P420 in addition to P450, suggesting the protein to be unstable. CYP3A5.11
      exhibited a 38% decrease in the V(max) for nifedipine metabolism, a 2.7-fold
      increase in the K(m), and a 4.4-fold decrease in the CL(int) of nifedipine
      compared with CYP3A5.1. A polymerase chain reaction-restriction fragment length
      polymorphism genotyping procedure was developed and used to genotype DNA of 500
      white individuals for CYP3A5*11. No additional examples of this allele were
      identified. In summary, individuals carrying the rare CYP3A5*11 allele are
      predicted to have lower metabolism of CYP3A5 substrates than individuals
      expressing CYP3A5*3.

PMID- 17035600
TI  - Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,
      trichloro-2,2-bis (p-chlorophenyl)ethane.
AB  - CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and
      intestine, contributes to the metabolism of approximately half the drugs in
      clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of
      steroid hormones and is involved in the bioactivation of environmental
      procarcinogens. The expression of CYP3A4 is affected by several stimuli,
      including environmental factors such as insecticides and pesticides. The o,p'
      1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises
      approximately 20% of technical grade DDT, which is an organochloride pesticide.
      We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in
      HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4
      expression, transactivation and electrophoretic mobility shift assays were
      carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through
      the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both
      an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in
      HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the
      intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher
      doses, a decrease of CYP3A4 inducibility was observed together with an increase
      in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly
      represses CYP3A4 transcription. The present study indicates that regulation of
      other genes under PXR control may be altered by o,p'-DDT exposure.

PMID- 17035601
TI  - A real-time fluorescence assay for measuring N-dealkylation.
AB  - A real-time fluorescence assay system using a series of 9-N-(alkylamino)acridine
      derivatives (methyl, ethyl, n-propyl, n-butyl, n-pentyl, and benzyl) that are N
      dealkylated to 9-aminoacridine (9AA) is described. The product, 9AA, is
      approximately 27-fold more fluorescent than the substrates using excitation and
      emission wavelengths of 405 and 455 nm, respectively. Tests using expressed
      CYP1A1, 1A2, 3A4, 3A5, 1B1, 2C9, 2C19, and 2D6 indicated that N-dealkylase
      activity is specific for CYP1A1 and CYP2D6. CYP2D6 N-dealkylated methyl, ethyl, n
      propyl, and n-butyl substrates, whereas CYP1A1 N-dealkylated these plus the n
      pentyl derivative. Activities using 5 microM 9-N-(alkylamino)acridine substrates
      ranged from 0.1 to 0.9 pmol 9AA/min/pmol P450. Kinetic constants for CYP1A1 N
      dealkylation of the 9-N-(methylamino)acridine (MAA) and 9-N-(ethylamino)acridine
      (EAA) were K(m) 1.09 +/- 0.68 and 0.35 +/- 0.21 microM and the V(max) 61.9 +/-
      48.5 and 113.8 +/- 8.4 pmol 9AA/min/pmol CYP1A1, respectively. Kinetic constants
      for CYP2D6 N-dealkylation of MAA and EAA were K(m) 7.9 +/- 5.4 and 3.2 +/- 1.6
      microM, and V(max) 501 +/- 35.4 and 702.7 +/- 257 pmol 9AA/min/pmol CYP2D6,
      respectively. The experimental binding energies (DeltaG(bind)) were calculated
      for MAA with CYP1A1 and CYP2D6 to be -8.266 and -7.074 kcal/mol, respectively.
      The DeltaG(bind) values for EAA with CYP1A1 and CYP2D6 were -8.950 and -7.618
      kcal/mol, respectively. The substrates were suitable for monitoring N-dealkylase
      activity in microsomal preparations (human, rat, and monkey hepatic preparations)
      and human hepatocellular carcinoma cell suspensions. Assays were conducted by
      monitoring reactions either in 96-well microtiter plates using a fluorescence
      plate reader or in cuvettes using a spectrofluorimeter.

PMID- 17035602
TI  - Cellular localization studies on human estrogen sulfotransferase SULT1E1 in human
      embryonic kidney 293 cells.
AB  - Human cytosolic sulfotransferase SULT1E1 catalyzes the sulfation of endogenous
      estrogens as well as xenobiotic estrogen-like chemicals. This reaction increases
      the water solubility of the molecule, which may affect its cellular distribution
      and biological activity. This could alter estrogen signaling to the estrogen
      receptor in human estrogen receptor-positive cells. The current work
      characterized the cellular distribution of SULT1E1 in the human embryonic kidney
      293 (HEK293) cell line using green fluorescent protein (GFP) tagging and
      immunochemistry methods. The GFP-tagged recombinant SULT1E1 protein was expressed
      and localized in the cytoplasm of HEK293 cells. By using a commercial anti
      SULT1E1 peptide antibody, a 35.7-kDa protein was detected in HEK293 cells via
      Western blot. The molecular mass of the protein detected suggested that it may be
      related to native SULT1E1 protein. However, reverse transcription-polymerase
      chain reaction (RT-PCR) with gene-specific primers could not confirm the presence
      of the SULT1E1 transcript in the total RNA sample of HEK293 cells. The
      discrepancy between protein and transcript data could be due to the instability
      of SULT1E1 mRNA or the specificity of the anti-SULT1E1 antibody used. In the
      present work, RT-PCR analysis with gene-specific primers also identified a
      transcript fragment of human estrogen-related receptor gamma. Future studies on
      the functional relationship between estrogen-related receptors and
      sulfotransferases are expected to provide additional insights into the
      physiological and toxicological roles of human estrogen sulfotransferases.

PMID- 17035603
TI  - An emerging role for relaxin as a renal vasodilator.

PMID- 17035604
TI  - Cyst number but not the rate of cystic growth is associated with the mutated gene
      in autosomal dominant polycystic kidney disease.
AB  - Data from serial renal magnetic resonance imaging of the Consortium of Radiologic
      Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD)
      population showed that cystic expansion occurs at a consistent rate per
      individual, although it is heterogeneous in the population, and that larger
      kidneys are associated with more rapid disease progression. The significance of
      gene type to disease progression is analyzed in this study of the CRISP cohort.
      Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and
      27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of
      cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst
      number increased with age, and more cysts were detected in PKD1 kidneys (P <
      0.0001). PKD1 is more severe because more cysts develop earlier, not because they
      grow faster, implicating the disease gene in cyst initiation but not expansion.
      These insights will inform the development of targeted therapies in autosomal
      dominant PKD.

PMID- 17035605
TI  - Chronic kidney disease progression.

PMID- 17035606
TI  - Apparent mineralocorticoid excess: report of six new cases and extensive personal
      experience.
AB  - In mineralocorticoid target tissues such as the cortical collecting duct in the
      kidney, the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is
      responsible for the peripheral inactivation of cortisol to cortisone, thereby
      protecting the mineralocorticoid receptor from inappropriate activation by
      cortisol. Mutations in the HSD11B2 gene cause the syndrome of apparent
      mineralocorticoid excess, an autosomal recessive form of inherited hypertension
      in which cortisol acts as a potent mineralocorticoid. Herein are described six
      new families with mutations in the HSD11B2 gene causing hypokalemic hypertension,
      with low plasma aldosterone and low renin levels in affected individuals,
      indicating mineralocorticoid hypertension. Profiling of urinary steroid
      metabolites showed decreased cortisol inactivation, with urinary
      tetrahydrocortisol and tetrahydrocortisone ratio (THF + 5alphaTHF)/THE ranging
      2.4 to 40 and nearly absent urinary free cortisone in all but one case. Genetic
      analysis of the HSD11B2 gene from these patients with apparent mineralocorticoid
      excess revealed distinct homozygous point mutations in four families, a compound
      heterozygous mutation in one family, and a large 23-bp exonic insert with
      frameshift and disruption of the amino acid sequence in another family.
      Expression studies of mutants that were expressed in HEK-293 cells showed marked
      reduction or abolition of 11betaHSD2 enzymatic activity. These cases are reviewed
      along with previous ones from the authors' extensive personal experience to
      highlight the importance of 11betaHSD2 in the understanding of a new biologic
      principle in hormone action, demonstrating that local metabolism of the
      glucocorticoid hormones into inactive derivatives by the enzyme 11betaHSD2 is one
      of the mechanisms that intervene to allow specific aldosterone regulatory
      effects.

PMID- 17035607
TI  - No improvement of patient or graft survival in transplant recipients treated with
      angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor
      blockers: a collaborative transplant study report.
AB  - It was reported recently that treatment of kidney transplant recipients with
      angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor
      blockers (ARB) is associated with strikingly improved long-term graft and patient
      survival. This finding has important implications for future posttransplantation
      therapy recommendations. In an analysis of 17,209 kidney and 1744 heart
      transplant recipients, an association of treatment with ACEI/ARB with improved
      transplant outcome could not be confirmed. It is concluded that recommendations
      for a widespread use of ACEI/ARB treatment in transplant recipients are
      unwarranted.

PMID- 17035608
TI  - Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and
      mechanisms of action.

PMID- 17035609
TI  - Proteomic analysis of urine in kidney transplant patients with BK virus
      nephropathy.
AB  - The differentiation of BK virus-associated renal allograft nephropathy (BKVAN)
      from acute allograft rejection (AR) in renal transplant recipients is an
      important clinical problem because the treatment can be diametrically opposite
      for the two conditions. The aim of this discovery-phase biomarker development
      study was to examine feasibility of developing a noninvasive method to
      differentiate BKVAN from AR. Surface-enhanced laser desorption/ionization (SELDI)
      time-of-flight mass spectrometry analysis was used to compare proteomic profiles
      of urine samples of 21 patients with BKVAN, 28 patients with AR (Banff Ia to
      IIb), and 29 patients with stable graft function. SELDI analysis showed proteomic
      profiles that were significantly different in the BKVAN group versus the AR and
      stable transplant groups. Peaks that corresponded to m/z values of 5.872, 11.311,
      11.929, 12.727, and 13.349 kD were significantly higher in patients with BKVAN.
      Bioinformatics analyses allowed distinction of profiles of patients with BKVAN
      from patients with AR and stable patients. SELDI profiles also showed a high
      degree of reproducibility. Proteomic analysis of urine may offer a noninvasive
      way to differentiate BKVAN from AR in clinical practice. The identification of
      individual proteomic peaks can improve further the clinical utility of this
      screening method.

PMID- 17035610
TI  - Renal fibroblasts and myofibroblasts in chronic kidney disease.

PMID- 17035611
TI  - How does proteinuria cause progressive renal damage?
AB  - The possibility that proteinuria may accelerate kidney disease progression to end
      stage renal failure has received support from the results of increasing numbers
      of experimental and clinical studies. Evidence indicating that this process
      occurs through multiple pathways, including induction of tubular chemokine
      expression and complement activation that lead to inflammatory cell infiltration
      in the interstitium and sustained fibrogenesis, is reviewed. Macrophages are
      prominent in the interstitial inflammatory infiltrate. This cell type mediates
      progression of renal injury to the extent that macrophage numbers in renal biopsy
      predict renal survival in patients with chronic renal disease. Chemoattractants
      and adhesive molecules for inflammatory cells are upregulated by excess
      ultrafiltered protein load of proximal tubular cells via activation of NF-kappaB
      dependent and NF-kappaB-independent pathways. This mechanism is a potential
      target for therapeutic approaches, as shown by beneficial effects of
      manipulations with inhibitory molecules of NF-kappaB activation or of chemokine
      receptors in experimental studies. Targeting complement synthesis or activation
      in proximal tubule might offer novel therapeutic opportunities. Finally, proximal
      tubular cell receptors for uptake of plasma proteins that are under investigation
      may provide activation signals on excess tubular protein handling.

PMID- 17035612
TI  - Acute uremia but not renal inflammation attenuates aseptic acute lung injury: a
      critical role for uremic neutrophils.
AB  - Acute renal failure (ARF) remains a major clinical challenge, especially in the
      intensive care setting. Mortality of ARF combined with acute lung injury (ALI) is
      even higher and may reach 80%. Recent studies have suggested a remote effect of
      ARF on pulmonary homeostasis. However, it is unknown whether and to what extent
      ARF clinically affects pulmonary function, in particular oxygenation. For
      elucidation of the impact of ARF on aseptic ALI, a murine two-hit model that
      consists of acute uremia (AU) and subsequent ALI was developed. AU was induced by
      renal ischemia-reperfusion (inflammatory AU) or bilateral nephrectomy
      (noninflammatory AU). ALI was initiated by intratracheal HCl instillation and
      characterized by severe, PMN-dependent decrease in arterial partial pressure of
      O(2) (>70%) in nonuremic mice. Uremic mice, by contrast, showed a significant
      protection from ALI (decrease in arterial partial pressure of O(2) <40%); this
      was independent of the type of AU. Reconstitution experiments, in which uremic
      neutrophils were injected into nonuremic mice and vice versa, identified uremic
      neutrophils as the primary mediators. Between normal and uremic neutrophils,
      there were no differences in apoptosis or superoxide production. Pulmonary
      recruitment of uremic neutrophils, however, was significantly attenuated compared
      with that of normal neutrophils. This defect was associated with altered surface
      expression of L-selectin; sialyl Lewis(x), an L-selectin counterreceptor,
      previously was proved to be critical in aseptic ALI. In conclusion, it is shown
      that AU but not renal inflammation attenuates aseptic, neutrophil-dependent ALI
      and exerts an anti-inflammatory effect by attenuating pulmonary neutrophil
      recruitment.

PMID- 17035613
TI  - Renin-angiotensin-aldosterone system and progression of renal disease.
AB  - Inhibition of the renin-angiotensin-aldosterone system (RAAS) is one of the most
      powerful maneuvers to slow progression of renal disease. Angiotensin II (AngII)
      has emerged in the past decade as a multifunctional cytokine that exhibits many
      nonhemodynamic properties, such as acting as a growth factor and profibrogenic
      cytokine, and even having proinflammatory properties. Many of these deleterious
      functions are mediated by other factors, such as TGF-beta and chemoattractants
      that are induced in the kidney by AngII. Moreover, understanding of the RAAS has
      become much more complex in recent years with the identification of novel
      peptides (e.g., AngIV) that could bind to specific receptors, elucidating
      deleterious effects, and non-angiotensin-converting enzyme (ACE)-mediated
      generation of AngII. The ability of renal cells to produce AngII in a
      concentration that is much higher than what is found in the systemic circulation
      and the observation that aldosterone may be engaged directly in profibrogenic
      processes independent of hypertension have added to the complexity of the RAAS.
      Even renin has now been identified to have a "life on its own" and mediates
      profibrotic effects via binding to specific receptors. Finally, drugs that are
      used to block the RAAS, such as ACE inhibitors or certain AngII type 1 receptor
      antagonists, may have properties on cells independent of AngII (ACE inhibitor
      mediated outside-inside signaling and peroxisome proliferator-activated receptor
      gamma stimulatory effects of certain sartanes). Although blockade of the RAAS
      with ACE inhibitors, AngII type 1 receptor antagonists, or the combination of
      both should be part of every strategy to slow progression of renal disease, a
      better understanding of the novel aspects of the RAAS should contribute to the
      development of innovative strategies not only to completely halt progression but
      also to induce regression of human renal disease.

PMID- 17035614
TI  - Partial neutralization of the acidogenic Western diet with potassium citrate
      increases bone mass in postmenopausal women with osteopenia.
AB  - Chronic acid loads are an obligate consequence of the high animal/grain protein
      content of the Western diet. The effect of this diet-induced metabolic acidosis
      on bone mass is controversial. In a randomized, prospective, controlled, double
      blind trial, 161 postmenopausal women (age 58.6 +/- 4.8 yr) with low bone mass (T
      score -1 to -4) were randomly assigned to 30 mEq of oral potassium (K) citrate
      (Kcitrate) or 30 mEq of K chloride (KCl) daily. The primary end point was the
      intergroup difference in mean percentage change in bone mineral density (BMD) at
      lumbar spine (L2 through L4) after 12 mo. Compared with the women who received
      KCl, women who received Kcitrate exhibited an intergroup increase in BMD (+/-SE)
      of 1.87 +/- 0.50% at L2 through L4 (P < 0.001), of 1.39 +/- 0.48% (P < 0.001) at
      femoral neck, and of 1.98 +/- 0.51% (P < 0.001) at total hip. Significant
      secondary end point intragroup changes also were found: Kcitrate increased L2
      through L4 BMD significantly from baseline at months 3, 9, and 12 and reached a
      month 12 increase of 0.89 +/- 0.30% (P < 0.05), whereas the KCl arm showed a
      decreased L2 through L4 BMD by -0.98 +/- 0.38% (P < 0.05), significant only at
      month 12. Intergroup differences for distal radius and total body were NS. The
      Kcitrate-treated group demonstrated a sustained and significant reduction in
      urinary calcium excretion and a significant increase in urinary citrate
      excretion, with increased citrate excretion indicative of sustained systemic
      alkalization. Urinary bone resorption marker excretion rates were significantly
      reduced by Kcitrate, and for deoxypyridinoline, the intergroup difference was
      significant. Urinary net acid excretion correlated inversely and significantly
      with the change in BMD in a subset of patients. Large and significant reductions
      in BP were observed for both K supplements during the entire 12 mo. Bone mass can
      be increased significantly in postmenopausal women with osteopenia by increasing
      their daily alkali intake as citrate, and the effect is independent of reported
      skeletal effects of K.

PMID- 17035615
TI  - The chronic kidney disease epidemic: stepping back and looking forward.
AB  - Estimating the prevalence of chronic kidney disease (CKD) is no simple task. The
      overall prevalence is relatively low but may be higher in select populations that
      are not accessible to surveys (e.g., certain ethnic groups, the sick or elderly).
      Moreover, the tests that define CKD lack precision and transportability to
      healthy populations. During the past decade, it is not clear that CKD has grown
      substantially. Some epidemiologic factors that are associated with CKD (obesity
      and diabetes) are increasing, whereas others (uncontrolled hypertension and
      smoking) are decreasing. Reasons for the discrepancy between a stable CKD
      population and ongoing ESRD growth remain speculative. There is evidence that
      ESRD rates may be stabilizing and that efforts to reduce progression in high-risk
      groups may be starting to show benefit. Expanding the definition of CKD and
      increasing detection may be required to reduce overall ESRD prevalence. One
      concern is that many of the well-defined high-risk patient groups (diabetes and
      black) are still undertreated. Increasing the investigation and treatment of low
      risk patients may not be the answer. Clinical inertia (failure to initiate or
      change therapy) may be a more significant and modifiable barrier toward reducing
      ESRD, and this deserves increased attention. Furthermore, reducing CKD prevalence
      will require controlling the precipitating causes. The incremental benefit of
      detecting CKD in low-risk patients, use of expensive therapies in CKD, or new
      strategies such as the treatment of prehypertension require solid evidence, not
      only of the variety that shows benefit (hard end points) but also to whom, when,
      and at what cost.

PMID- 17035616
TI  - Posttransplantation anemia at 12 months in kidney recipients treated with
      mycophenolate mofetil: risk factors and implications for mortality.
AB  - Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil
      era, its impact on patient survival is unknown. This retrospective cohort study
      characterized factors that are associated with PTA 12 mo after transplantation in
      mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA
      affects outcomes. The records of 626 kidney recipients were examined for presence
      of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with
      covariates that had unadjusted relationships, investigated both risk factors for
      12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was
      72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic
      regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI]
      5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3
      mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo
      PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a
      higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than
      nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI
      1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008),
      age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C
      seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with
      mortality. There was no interaction between 12-mo PTA and serum creatinine. In
      conclusion, 12-mo PTA is associated with an increased risk for patient death. The
      presence of anemia 3 mo after kidney transplantation is a major determinant of 12
      mo PTA. PTA in kidney recipients therefore should be defined by its persistence
      or occurrence beyond the third posttransplantation month.

PMID- 17035617
TI  - Influence of recombinant human relaxin on renal hemodynamics in healthy
      volunteers.
AB  - Maternal renal hemodynamic adaptation to human pregnancy is one of the most
      dramatic of all physiologic changes, but the factors that are responsible have
      remained elusive. In rat pregnancy, there are comparable renal hemodynamic
      changes, and in this species there is comprehensive evidence that the ovarian
      hormone relaxin (RLX) is responsible. This study investigated the renal effects
      of recombinant human RLX (rhRLX) in humans. Eleven volunteers (six male, five
      female) received intravenous infusions of rhRLX over 5 h at an infusion rate that
      was chosen to sustain serum concentrations that are comparable to early
      pregnancy. The renal clearances of inulin and para-aminohippurate were used to
      measure GFR and renal plasma flow, respectively. Irrespective of gender, renal
      plasma flow was increased by 47% compared with baseline levels (P < 0.0001), but
      no significant change was observed in GFR. There were no side effects or adverse
      reactions of rhRLX given as an intravenous infusion, and the data suggest that
      RLX indeed may be one of the elusive renal vasodilatory factors in human
      pregnancy. Further work is necessary to elucidate the complimentary factors that
      permit the concomitant increase in GFR during pregnancy.

PMID- 17035619
TI  - Serial Aspergillus antigen monitoring in pediatric bone marrow transplant
      patients.
AB  - Invasive aspergillosis carries a high mortality rate in immunocompromised
      patients, such as bone marrow transplant patients. Favorable outcomes are
      dependent on early detection and treatment. Positive galactomannan antigenemia
      has been included as a microbiological criterion for probable or possible
      diagnosis of invasive aspergillosis. Detection of circulating Aspergillus DNA in
      the first positive galactomannan sample, with serial monitoring, could help in
      diagnosis of invasive aspergillosis in bone marrow transplant patients. Morbidity
      and mortality from aspergillosis can possibly be reduced if an early diagnosis is
      made and appropriate treatment initiated. An effective and accurate way of early
      detection of invasive aspergillosis is serial Aspergillus antigen monitoring.

PMID- 17035620
TI  - An examination of fatigue in advanced childhood cancer.
AB  - Fatigue is a complex phenomenon without a widely accepted definition, and is one
      of the least explained phenomena of advanced disease. A great deal of work and
      research has been done to explore the experience, incidence, and management of
      fatigue in children with cancer. Fatigue remains, however, a source of suffering
      for children with advanced disease and their families. The knowledge we have
      gained from the study of fatigue in children receiving antineoplastic therapy can
      be applied to children during this phase of their illness. The goal of this
      article is to address the incidence of fatigue in the advanced stage of illness,
      review the literature regarding fatigue in pediatric oncology, and propose how
      such findings may be applicable to children in the later stages of their illness.

PMID- 17035621
TI  - Assessing procedural pain in children with cancer in Beirut, Lebanon.
AB  - This study describes the relationship between different indicators of pain,
      including self-reports, behavioral observations, and physiological measures, in
      children with cancer undergoing invasive procedures. Forty-five children between
      the ages of 4 and 10 years were evaluated while undergoing Port-a-Cath access.
      The study was conducted in the outpatient clinics of the Children's Cancer Center
      in Beirut, Lebanon. Children used 2 self-report measures of pain (the Wong-Baker
      FACES Pain Rating Scale and an adaptation of the FACES, the DOLLS). Parents and
      nurses assessed the child's pain on the FACES and the child's distress on the
      Observational Scale of Behavioral Distress-Revised. Nurses recoded behavioral
      observations as well as physiological responses to pain. There was a high degree
      of consistency between the self-reports and moderate to high correlations between
      self-reports, behavioral parameters, and physiological parameters, suggesting
      that accurate pain assessments can be made by both nurses and parents. The
      results also demonstrate adequate validity and reliability of the DOLLS scale in
      a Lebanese population, in addition to being the preferred assessment tool for all
      the children in the study.

PMID- 17035622
TI  - The role of cognitive remediation in childhood cancer survivors experiencing
      neurocognitive late effects.
AB  - With the increasing number of children becoming long-term cancer survivors, it
      has become evident that these survivors are experiencing long-term neurocognitive
      deficits. Many of these deficits have been found to be the result of cancer
      related therapies including intravenous and intrathecal chemotherapy and cranial
      radiation. These neurocognitive deficits include learning disabilities, cognitive
      deficits, attention disorders, and difficulties with memory. Cognitive
      remediation therapy uses a systematic approach to learning strategies that is
      aimed to equip these affected children with proper, effective, and proven
      learning strategies. This article will briefly discuss the neurocognitive
      deficits experienced by long-term childhood cancer survivors. Cognitive
      remediation therapy will then be introduced with specific attention to the
      cognitive remediation program developed by Butler and Copeland. Finally,
      implications for practice and future research will be discussed.

PMID- 17035623
TI  - The effect of clinic-based health promotion education on perceived health status
      and health promotion behaviors of adolescent and young adult cancer survivors.
AB  - More than 70% of children/adolescents diagnosed with cancer are long-term
      survivors. Little is known about the health perceptions and practices of this
      population, and limited previous studies have come exclusively from a risk
      reduction/health protection model rather than a health promotion model. This
      study was conducted to describe the perceived health status and health-promoting
      behaviors of adolescent/young adult cancer survivors. This study used Pender's
      revised health promotion model; perceived health status and health-promoting
      behaviors were measured using the General Health Index (GHRI) and the Health
      Promoting Lifestyle Profile II (HPLP-II). The sample consisted of 60 cancer
      survivors 2 years after completion of cancer treatment and attending a
      survivorship clinic. Mean baseline scores for the GHRI (76.66; SD, 10.41)
      indicate perceived health status is positive and similar to normative (noncancer
      survivor) adolescent/young adult samples. Surprisingly, there was no correlation
      between scores on the GHRI and the HPLP-II in this sample (r = 0.03).

PMID- 17035624
TI  - Transitioning to survivorship: a pilot study.
AB  - There are no clear transition guidelines for adolescent and young adult cancer
      patients, their parents, and their primary care providers (PCPs) when completing
      active therapy and within the first few years after therapy. The purpose of this
      pilot study was to identify needs and concerns of recently treated adolescent
      cancer patients and their parents, young adult cancer survivors, and the
      community PCPs of adolescent patients. Four focus group interviews were conducted
      with survivors and parents, and 3 in-depth interviews were conducted with PCPs.
      All interviews were audiotaped and transcribed for content analysis. A range of
      needs were identified, including lack of adequate written and verbal information
      about their prior treatment, its potential side effects, and appropriate follow
      up care. The best sources for education were identified as the primary
      oncologist, nurse practitioner, or nurse. At completion of treatment, parents and
      adult survivors felt a lack of psychosocial support. Suggestions from
      participants included use of informational videos for survivors, weekend
      education and support programs, ongoing support groups, use of the Internet, and
      educational newsletters. The PCPs reported a lack of general pediatric oncology
      knowledge and specific patient information, time constraints in their patient
      schedules, and having few survivors in their practices as barriers to optimal
      survivorship care. Further research is needed to look at the unmet educational
      and psychological needs of childhood cancer survivors and their parents during
      the critical time when they transition off treatment.

PMID- 17035625
TI  - Development of a screening assay for surrogate markers of CHK1 inhibitor-induced
      cell cycle release.
AB  - Chk1 is a key regulator of the S and G2/M checkpoints and is activated following
      DNA damage by agents such as the topoisomerase I inhibitor camptothecin (CPT). It
      has been proposed that Chk1 inhibitors used in combination with such a DNA
      damaging agent to treat tumors would potentiate cytotoxicity and increase the
      therapeutic index, particularly in tumors lacking functional p53. The aim of this
      study was to determine whether gene expression analysis could be used to inform
      lead optimization of a novel series of Chk1 inhibitors. The candidate small
      molecule Chk1 inhibitors were used in combination with CPT to identify potential
      markers of functional Chk1 inhibition, as well as resulting cell cycle
      progression, using cDNA-based microarrays. Differential expression of several of
      these putative marker genes was further validated by RT-PCR for use as a medium
      throughput assay. In the presence of DNA damage, Chk1 inhibitors altered CPT
      dependent effects on the expression of cell cycle and DNA repair genes in a
      manner consistent with a Chk1-specific mechanism of action. Furthermore,
      differential expression of selected marker genes, cyclin E2, EGR1, and DDIT3, was
      dose dependent for Chk1 inhibition. RT-PCR results for these genes following
      treatment with a panel of Chk1 inhibitors showed a strong correlation between
      marker gene response and the ability of each compound to abrogate cell cycle
      arrest in situ following CPT-induced DNA damage. These results demonstrate the
      utility of global expression analysis to identify surrogate markers, providing an
      alternative method for rapid compound characterization to support advancement
      decisions in early drug discovery.

PMID- 17035628
TI  - GPI-anchored proteins and free GPI glycolipids of procyclic form Trypanosoma
      brucei are nonessential for growth, are required for colonization of the tsetse
      fly, and are not the only components of the surface coat.
AB  - The procyclic form of Trypanosoma brucei exists in the midgut of the tsetse fly.
      The current model of its surface glycocalyx is an array of rod-like procyclin
      glycoproteins with glycosylphosphatidylinositol (GPI) anchors carrying sialylated
      poly-N-acetyllactosamine side chains interspersed with smaller sialylated poly-N
      acetyllactosamine-containing free GPI glycolipids. Mutants for TbGPI12, deficient
      in the second step of GPI biosynthesis, were devoid of cell surface procyclins
      and poly-N-acetyllactosamine-containing free GPI glycolipids. This major
      disruption to their surface architecture severely impaired their ability to
      colonize tsetse fly midguts but, surprisingly, had no effect on their morphology
      and growth characteristics in vitro. Transmission electron microscopy showed that
      the mutants retained a cell surface glycocalyx. This structure, and the viability
      of the mutants in vitro, prompted us to look for non-GPI-anchored parasite
      molecules and/or the adsorption of serum components. Neither were apparent from
      cell surface biotinylation experiments but [3H]glucosamine biosynthetic labeling
      revealed a group of previously unidentified high apparent molecular weight
      glycoconjugates that might contribute to the surface coat. While characterizing
      GlcNAc-PI that accumulates in the TbGPI12 mutant, we observed
      inositolphosphoceramides for the first time in this organism.

PMID- 17035629
TI  - Bypassing the catalytic activity of SIR2 for SIR protein spreading in
      Saccharomyces cerevisiae.
AB  - Sir protein spreading along chromosomes and silencing in Saccharomyces cerevisiae
      requires the NAD+-dependent histone deacetylase activity of Sir2p. We tested
      whether this requirement could be bypassed at the HM loci and telomeres in cells
      containing a stably expressed, but catalytically inactive mutant of Sir2p, sir2
      345p, plus histone mutants that mimic the hypoacetylated state normally created
      by Sir2p. Sir protein spreading was rescued in sir2-345 mutants expressing
      histones in which key lysine residues in their N-termini had been mutated to
      arginine. Mating in these mutants was also partially restored upon overexpression
      of Sir3p. Together, these results indicate that histone hypoacetylation is
      sufficient for Sir protein spreading in the absence of production of 2'-O-acetyl
      ADP ribose by sir2p and Sir2p's enzymatic function for silencing can be bypassed
      in a subset of cells in a given population. These results also provide genetic
      evidence for the existence of additional critical substrates of Sir2p for
      silencing in vivo.

PMID- 17035630
TI  - Functional analysis of AP-2 alpha and mu2 subunits.
AB  - The AP-2 adaptor complex plays a key role in cargo recognition and clathrin
      coated vesicle formation at the plasma membrane. To investigate the functions of
      individual binding sites and domains of the AP-2 complex in vivo, we have stably
      transfected HeLa cells with wild-type and mutant small interfering RNA-resistant
      alpha and mu2 subunits and then used siRNA knockdowns to deplete the endogenous
      proteins. Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation
      site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed
      by transferrin uptake. In contrast, removing the C-terminal appendage domain of
      alpha, or mutating the PtdIns(4,5)P2 binding site of mu2, has no apparent effect.
      However, adding a C-terminal GFP tag to alpha renders it completely
      nonfunctional. These findings demonstrate that there is some functional
      redundancy in the binding sites of the various AP-2 subunits, because no single
      mutation totally abolishes function. They also help to explain why GFP-tagged AP
      2 never appears to leave the plasma membrane in some live cell imaging studies.
      Finally, they establish a new model system that can be used both for additional
      structure-function analyses, and as a way of testing tagged constructs for
      function in vivo.

PMID- 17035631
TI  - Ubc9 regulates mitosis and cell survival during zebrafish development.
AB  - Many proteins are modified by conjugation with Sumo, a gene-encoded, ubiquitin
      related peptide, which is transferred to its target proteins via an enzymatic
      cascade. A central component of this cascade is the E2-conjugating enzyme Ubc9,
      which is highly conserved across species. Loss-of-function studies in yeast,
      nematode, fruit fly, and mouse blastocystes point to multiple roles of Ubc9
      during cell cycle regulation, maintenance of nuclear architecture, chromosome
      segregation, and viability. Here we show that in zebrafish embryos, reduction of
      Ubc9 activity by expression of a dominant negative version causes widespread
      apoptosis, similar to the effect described in Ubc9-deficient mice. However,
      antisense-based knock down of zygotic ubc9 leads to much more specific defects in
      late proliferating tissues, such as cranial cartilage and eyes. Affected
      cartilaginous elements are of relatively normal size and shape, but consist of
      fewer and larger cells. Stainings with mitotic markers and 5-Bromo-2'
      deoxyuridine incorporation studies indicate that fewer chondrocyte precursors are
      in mitosis, whereas the proportion of cells in S-phase is unaltered.
      Consistently, FACS analyses reveal an increase in the number of cells with a DNA
      content of 4n or even 8n. Our data indicate an in vivo requirement of Ubc9 for
      G2/M transition and/or progression through mitosis during vertebrate
      organogenesis. Failed mitosis in the absence of Ubc9 is not necessarily coupled
      with cell death. Rather, cells can continue to replicate their DNA, grow to a
      larger size, and finish their normal developmental program.

PMID- 17035632
TI  - Reconstruction of the kinetochore during meiosis in fission yeast
      Schizosaccharomyces pombe.
AB  - During the transition from mitosis to meiosis, the kinetochore undergoes
      significant reorganization, switching from a bipolar to a monopolar orientation.
      To examine the centromere proteins that are involved in fundamental
      reorganization in meiosis, we observed the localization of 22 mitotic and 2
      meiotic protein components of the kinetochore during meiosis in living cells of
      the fission yeast. We found that the 22 mitotic proteins can be classified into
      three groups: the Mis6-like group, the NMS (Ndc80-Mis12-Spc7) group, and the DASH
      group, based on their meiotic behavior. Mis6-like group proteins remain at the
      centromere throughout meiosis. NMS group proteins disappear from the centromere
      at the onset of meiosis and reappear at the centromere in two steps in late
      prophase. DASH group proteins appear shortly before metaphase of meiosis I. These
      observations suggest that Mis6-like group proteins constitute the structural
      basis of the centromere and that the NMS and DASH group proteins reassemble to
      establish the functional metaphase kinetochore. On the other hand, the meiosis
      specific protein Moa1, which plays an important role in forming the meiotic
      monopolar kinetochore, is loaded onto the centromere significantly earlier than
      the NMS group, whereas another meiosis-specific protein, Sgo1, is loaded at times
      similar to the NMS group.

PMID- 17035633
TI  - Wnt5a signaling induces proliferation and survival of endothelial cells in vitro
      and expression of MMP-1 and Tie-2.
AB  - Wnts are lipid-modified secreted glycoproteins that regulate diverse biological
      processes. We report that Wnt5a, which functions in noncanonical Wnt signaling,
      has activity on endothelial cells. Wnt5a is endogenously expressed in human
      primary endothelial cells and is expressed in murine vasculature at several sites
      in mouse embryos and tissues. Expression of exogenous Wnt5a in human endothelial
      cells promoted angiogenesis. Wnt5a induced noncanonical Wnt signaling in
      endothelial cells, as measured by Dishevelled and ERK1/2 phosphorylation, and
      inhibition of canonical Wnt signaling, a known property of Wnt5a. Wnt5a induced
      endothelial cell proliferation and enhanced cell survival under serum-deprived
      conditions. The Wnt5a-mediated proliferation was blocked by Frizzled-4
      extracellular domain. Wnt5a expression enhanced capillary-like network formation,
      whereas reduction of Wnt5a expression decreased network formation. Reduced Wnt5a
      expression inhibited endothelial cell migration. Screening for Wnt5a-regulated
      genes in cultured endothelial cells identified several encoding angiogenic
      regulators, including matrix metalloproteinase-1, an interstitial collagenase,
      and Tie-2, a receptor for angiopoietins. Thus, Wnt5a acts through noncanonical
      Wnt signaling to promote angiogenesis.

PMID- 17035634
TI  - The unfolded protein response transducer Ire1p contains a nuclear localization
      sequence recognized by multiple beta importins.
AB  - The Ire1p transmembrane receptor kinase/endonuclease transduces the unfolded
      protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus in
      Saccharomyces cerevisiae. In this study, we analyzed the capacity of a highly
      basic sequence in the linker region of Ire1p to function as a nuclear
      localization sequence (NLS) both in vivo and in vitro. This 18-residue sequence
      is capable of targeting green fluorescent protein to the nucleus of yeast cells
      in a process requiring proteins involved in the Ran GTPase cycle that facilitates
      nuclear import. Mutagenic analysis and importin binding studies demonstrate that
      the Ire1p linker region contains overlapping potential NLSs: at least one
      classical NLS (within sequences 642KKKRKR647 and/or 653KKGR656) that is
      recognized by yeast importin alpha (Kap60p) and a novel betaNLS
      (646KRGSRGGKKGRK657) that is recognized by several yeast importin beta
      homologues. Kinetic binding data suggest that binding to importin beta proteins
      would predominate in vivo. The UPR, and in particular ER stress-induced HAC1 mRNA
      splicing, is inhibited by point mutations in the Ire1p NLS that inhibit nuclear
      localization and also requires functional RanGAP and Ran GEF proteins. The NLS
      dependent nuclear localization of Ire1p would thus seem to be central to its role
      in UPR signaling.

PMID- 17035635
TI  - Extracellular signal-regulated kinase 1/2 activity is not required in mammalian
      cells during late G2 for timely entry into or exit from mitosis.
AB  - Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be
      required in mammalian cells for timely entry into and exit from mitosis (i.e.,
      the G2-mitosis [G2/M] and metaphase-anaphase [M/A] transitions). However, it is
      unclear whether this involvement reflects a direct requirement for ERK1/2
      activity during these transitions or for activating gene transcription programs
      at earlier stages of the cell cycle. To examine these possibilities, we followed
      live cells in which ERK1/2 activity was inhibited through late G2 and mitosis. We
      find that acute inhibition of ERK1/2 during late G2 and through mitosis does not
      affect the timing of the G2/M or M/A transitions in normal or transformed human
      cells, nor does it impede spindle assembly, inactivate the p38 stress-activated
      checkpoint during late G2 or the spindle assembly checkpoint during mitosis.
      Using CENP-F as a marker for progress through G2, we also show that sustained
      inhibition of ERK1/2 transiently delays the cell cycle in early/mid-G2 via a p53
      dependent mechanism. Together, our data reveal that ERK1/2 activity is required
      in early G2 for a timely entry into mitosis but that it does not directly
      regulate cell cycle progression from late G2 through mitosis in normal or
      transformed mammalian cells.

PMID- 17035637
TI  - Effect of transgene concentration, flanking matrix attachment regions, and RecA
      coating on the efficiency of mouse transgenesis mediated by intracytoplasmic
      sperm injection.
AB  - Intracytoplasmic sperm injection (ICSI) of DNA-loaded sperm cells has been shown
      to be a valuable tool for the production of transgenic animals, especially when
      DNA constructs with submegabase magnitude are used. In order to optimize and to
      understand the mechanism of the ICSI-mediated transgenesis, we have evaluated the
      impact of transgene DNA concentration, transgene flanking with nuclear matrix
      attachment regions (MARs), and the use of recombinase A (RecA)-coated DNA on the
      efficiency of mouse transgenesis production by ICSI. Presented data include
      assays with three DNA constructs; an enhanced green fluorescent protein (EGFP)
      plasmid of 5.4 kb, this plasmid flanked with two MAR elements (2.3 Kb of the
      human beta-interferon domain boundaries), and a yeast artificial chromosome (YAC)
      construct of approximately 510 kb (the largest transgenic construct introduced by
      ICSI that we have seen reported). ICSI-mediated transgenesis was done in the B6D2
      mouse strain using different concentrations for each construct. Analysis of
      generated data indicated that ICSI allows the use of higher DNA concentrations
      than the ones used for pronuclear microinjection, however, when a certain
      threshold is exceeded, embryo/fetal viability decrease dramatically. In addition,
      independently of the transgene concentration tested, transgene flanking with MAR
      sequences did not have a significant impact on the efficiency of this
      transgenesis method. Finally, we observed that although the overall efficiency of
      ICSI-mediated transgenesis with fresh spermatozoa and RecA-complexed DNA was
      similar to the one obtained with the common ICSI-mediated transgenesis approach
      with frozen-thawed spermatozoa and RecA free DNA, this method was not as
      efficient in maintaining a low frequency of founder animal mosaicism, suggesting
      that different mechanisms of transgene integration might result from each
      procedure.

PMID- 17035636
TI  - A nuclear function of Hu proteins as neuron-specific alternative RNA processing
      regulators.
AB  - Recent advances in genome-wide analysis of alternative splicing indicate that
      extensive alternative RNA processing is associated with many proteins that play
      important roles in the nervous system. Although differential splicing and
      polyadenylation make significant contributions to the complexity of the nervous
      system, our understanding of the regulatory mechanisms underlying the neuron
      specific pathways is very limited. Mammalian neuron-specific embryonic lethal
      abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding
      proteins implicated in neuronal differentiation and maintenance. It has been
      established that Hu proteins increase expression of proteins associated with
      neuronal function by up-regulating mRNA stability and/or translation in the
      cytoplasm. We report here a novel function of these proteins as RNA processing
      regulators in the nucleus. We further elucidate the underlying mechanism of this
      regulation. We show that in neuron-like cells, Hu proteins block the activity of
      TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that
      promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide
      (CGRP) pre-mRNA processing. These studies define not only the first neuron
      specific regulator of the calcitonin/CGRP system but also the first nuclear
      function of Hu proteins.

PMID- 17035638
TI  - Identification, culture, and characterization of germline stem cell-like cells in
      chicken testes.
AB  - We recently succeeded in inducing germline transmission by transferring chicken
      testicular cells into heterologous testes. This study was designed subsequently
      to identify pluripotent cells in the testicular cells, which would induce the
      germline transmission. Testicular cells retrieved from juvenile (4-wk-old) or
      adult (24-wk-old) White Leghorn (WL) chickens were stained with germ cell
      specific markers anti-SSEA1, anti-SSEA3, anti-SSEA4, anti-EMA1, anti-ITGA6, and
      anti-ITGB1 antibodies; 2C9; and lectin-Solanum tuberosum agglutinin (STA). The
      percentages of the cells that were positive for each marker were within the
      ranges of 0.33% -0.44% and 0.029%-0.072% of the total testicular cell population
      in the juvenile and adult, respectively, and significant (P < 0.0002) differences
      were detected between the ages. When 1 x 10(6) testicular cells were cultured in
      Dulbecco minimum essential medium-based medium supplemented with leukemia
      inhibitory factor (LIF), basic fibroblast growth factor (FGF2), and/or
      insulinlike growth factor 1 (IGF1), colony formation was detected only in
      LIF++FGF2-containing or LIF+FGF2+IGF1-containing medium during primary culture,
      and the supplementation of LIF+FGF2+IGF1 was the most efficient for maintaining
      the colony-forming cells through subculture. The established cells retrieved at
      the end of the primary culture or the 20th subpassage were positive for chicken
      germ cell-specific periodic acid-Schiff (PAS), EMA1, 2C9, SSEA1, SSEA3, SSEA4,
      ITGA6, and ITGB1; and lectin-STA markers (evaluated after 11th subpassage).
      Double staining of lectin-STA with anti-SSEA1, anti-SSEA3, anti-SSEA4, anti
      ITGA6, and anti-ITGB1 also was possible. They differentiated spontaneously into
      embryoid bodies after being cultured in LIF-free medium. We conclude that
      germline stem cell-like cells are present in chicken testicular cells retrieved
      from both juvenile and adult testes, which can be identified with the specific
      markers for primordial germ cells or embryonic germ cells.

PMID- 17035639
TI  - The cytotrophoblast layer of human chorionic villi becomes thinner but maintains
      its structural integrity during gestation.
AB  - Chorionic villi in the human placenta serve as essential structures in
      fetomaternal exchanges. According to the embryology and placentology literature,
      during the first trimester, the cytotrophoblast (CTB) layer that is subjacent to
      the syncytiotrophoblast (STB) and supported by a basal lamina is nearly complete,
      but later, it becomes discontinuous. In the present study, we investigated the
      structural integrity of the CTB layer in the normal villous tree by advanced
      microscopy techniques using an antibody to hepatocyte growth factor (HGF)
      activator inhibitor type 1 (SPINT1), a potent inhibitor of HGF activators
      expressed exclusively on villous CTB. In full-term placenta, the cell surface of
      the CTB layer was spread over the basal lamina but was not interrupted.
      Morphometric analysis showed that throughout the villous tree, 80% of the
      continuity of the CTB layer of full-term placenta and 90% of that of first
      trimester placenta were preserved. Gestation was accompanied by unique structural
      change in the basal domain of the trophoblast layer. The initially cuboidal
      shaped CTB cells were transformed to flat cells with many cellular processes
      that, together with those of the adjacent STB, eventually covered the trophoblast
      basal lamina in a complex network of interdigitations. In addition, the
      expression levels of SPINT1, ST14, HGF, and MET mRNAs in the villous tree
      increased over the course of gestation. These results suggest that the structural
      integrity of the SPINT1-positive CTB layer may play an important role in villous
      differentiation and in maintenance of the villous tree via the HGF signaling
      system during gestation.

PMID- 17035640
TI  - In the absence of the mouse DNA/RNA-binding protein MSY2, messenger RNA
      instability leads to spermatogenic arrest.
AB  - MSY2 is a member of the Y-box family of proteins solely expressed in male and
      female germ cells. In the male, MSY2 serves as a coactivator of transcription by
      binding to a consensus promoter element present in many germ cell-specific genes.
      In the nucleus, MSY2 marks specific mRNAs for cytoplasmic storage, stabilization,
      and suppression of translation. The inactivation of MSY2 by gene targeting leads
      to spermatogenic arrest and infertility. In testes of mice lacking MSY2,
      incomplete nuclear condensation is prominent in later-stage spermatids at the
      time of massive spermatid loss. Because MSY2 interacts with DNA and mRNAs, there
      are several distinct sites of action, which could be disrupted in mice that lack
      MSY2, resulting in the arrest of spermatogenesis. To define the molecular
      cause(s) of the spermatogenic arrest in mice lacking MSY2, transcriptional and
      posttranscriptional processes were assayed. Transcription, mRNA processing, and
      mRNA intracellular transport appear normal in the absence of MSY2. However, a
      redistribution of mRNAs from ribonucleoprotein particles to polysomes and marked
      decreases were detected for many meiotic and postmeiotic germ cell mRNAs,
      including the mRNAs encoding the transition proteins and protamines. This
      suggests that increased mRNA instability is a likely cause of the male
      infertility in Msy2-null mice.

PMID- 17035641
TI  - Regulated mitochondrial DNA replication during oocyte maturation is essential for
      successful porcine embryonic development.
AB  - Cellular ATP is mainly generated through mitochondrial oxidative phosphorylation,
      which is dependent on mitochondrial DNA (mtDNA). We have previously demonstrated
      the importance of oocyte mtDNA for porcine and human fertilization. However, the
      role of nuclear-encoded mitochondrial replication factors during oocyte and
      embryo development is not yet understood. We have analyzed two key factors,
      mitochondrial transcription factor A (TFAM) and polymerase gamma (POLG), to
      determine their role in oocyte and early embryo development. Competent and
      incompetent oocytes, as determined by brilliant cresyl blue (BCB) dye, were
      assessed intermittently during the maturation process for TFAM and POLG mRNA
      using real-time RT-PCR, for TFAM and POLG protein using immunocytochemistry, and
      for mtDNA copy number using real-time PCR. Analysis was also carried out
      following treatment of maturing oocytes with the mtDNA replication inhibitor,
      2',3'-dideoxycytidine (ddC). Following in vitro fertilization, preimplantation
      embryos were also analyzed. Despite increased levels of TFAM and POLG mRNA and
      protein at the four-cell stage, no increase in mtDNA copy number was observed in
      early preimplantation development. To compensate for this, mtDNA appeared to be
      replicated during oocyte maturation. However, significant differences in nuclear
      encoded regulatory protein expression were observed between BCB(+) and BCB(-)
      oocytes and between untreated oocytes and those treated with ddC. These changes
      resulted in delayed mtDNA replication, which correlated to reduced fertilization
      and embryonic development. We therefore conclude that adherence to the regulation
      of the timing of mtDNA replication during oocyte maturation is essential for
      successful embryonic development.

PMID- 17035642
TI  - CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes.
AB  - In the mammalian testis, spermatogenesis is initiated from a subset of stem cells
      belonging to undifferentiated type A spermatogonia. In spite of the biologic
      significance of undifferentiated type A spermatogonia, little is known about
      their behavior and properties because of a lack of specific cell surface markers.
      Here we show that CDH1 (previously known as E-cadherin) is expressed specifically
      in undifferentiated type A spermatogonia in the mouse testis. Histologic analysis
      showed that CDH1-positive cells had all the characteristics of undifferentiated
      type A spermatogonia. Whole-mount immunohistochemistry showed that CDH1-positive
      cells made clusters mainly comprising one, two, four, or eight cells. They
      survived after administration of the cytotoxic agent busulfan to mice, and then
      regenerated seminiferous epithelia. Transplantation experiments showed that only
      CDH1-positive cells had colonizing activity in the recipient testis. Our data
      clearly demonstrated that spermatogenic stem cells reside among undifferentiated
      type A spermatogonia, which express CDH1.

PMID- 17035643
TI  - Videos in clinical medicine. Thoracentesis.

PMID- 17035644
TI  - Body of research--ownership and use of human tissue.

PMID- 17035645
TI  - Doctors on strike--the crisis in German health care delivery.

PMID- 17035646
TI  - The two-edged sword of curing childhood cancer.

PMID- 17035647
TI  - Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's
      disease.
AB  - BACKGROUND: Second-generation (atypical) antipsychotic drugs are widely used to
      treat psychosis, aggression, and agitation in patients with Alzheimer's disease,
      but their benefits are uncertain and concerns about safety have emerged. We
      assessed the effectiveness of atypical antipsychotic drugs in outpatients with
      Alzheimer's disease. METHODS: In this 42-site, double-blind, placebo-controlled
      trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or
      agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per
      day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per
      day), or placebo. Doses were adjusted as needed, and patients were followed for
      up to 36 weeks. The main outcomes were the time from initial treatment to the
      discontinuation of treatment for any reason and the number of patients with at
      least minimal improvement on the Clinical Global Impression of Change (CGIC)
      scale at 12 weeks. RESULTS: There were no significant differences among
      treatments with regard to the time to the discontinuation of treatment for any
      reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks),
      risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The
      median time to the discontinuation of treatment due to a lack of efficacy favored
      olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine
      (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of
      treatment due to adverse events or intolerability favored placebo. Overall, 24%
      of patients who received olanzapine, 16% of patients who received quetiapine, 18%
      of patients who received risperidone, and 5% of patients who received placebo
      discontinued their assigned treatment owing to intolerability (P=0.009). No
      significant differences were noted among the groups with regard to improvement on
      the CGIC scale. Improvement was observed in 32% of patients assigned to
      olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to
      risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS:
      Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs
      for the treatment of psychosis, aggression, or agitation in patients with
      Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548
      [ClinicalTrials.gov].).

PMID- 17035648
TI  - Microscopic-observation drug-susceptibility assay for the diagnosis of TB.
AB  - BACKGROUND: New diagnostic tools are urgently needed to interrupt the
      transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid,
      sensitive detection of tuberculosis and multidrug-resistant tuberculosis in
      sputum has been demonstrated in proof-of-principle studies of the microscopic
      observation drug-susceptibility (MODS) assay, in which broth cultures are
      examined microscopically to detect characteristic growth. METHODS: In an
      operational setting in Peru, we investigated the performance of the MODS assay
      for culture and drug-susceptibility testing in three target groups: unselected
      patients with suspected tuberculosis, prescreened patients at high risk for
      tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized
      patients infected with the human immunodeficiency virus. We compared the MODS
      assay head-to-head with two reference methods: automated mycobacterial culture
      and culture on Lowenstein-Jensen medium with the proportion method. RESULTS: Of
      3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium
      tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for
      automated mycobacterial culture, and 84.0% for Lowenstein-Jensen culture
      (P<0.001); the median time to culture positivity was 7 days, 13 days, and 26
      days, respectively (P<0.001), and the median time to the results of
      susceptibility tests was 7 days, 22 days, and 68 days, respectively. The
      incremental benefit of a second MODS culture was minimal, particularly in
      patients at high risk for tuberculosis or multidrug-resistant tuberculosis.
      Agreement between MODS and the reference standard for susceptibility was 100% for
      rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for
      multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa
      values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively). CONCLUSIONS: A single
      MODS culture of a sputum sample offers more rapid and sensitive detection of
      tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard
      methods used.

PMID- 17035649
TI  - A self-regulation program for maintenance of weight loss.
AB  - BACKGROUND: Since many successful dieters regain the weight they lose, programs
      that teach maintenance skills are needed. We developed a maintenance program
      based on self-regulation theory and tested the efficacy of delivering the program
      face to face or over the Internet. METHODS: We randomly assigned 314 participants
      who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of
      three groups: a control group, which received quarterly newsletters (105
      participants), a group that received face-to-face intervention (105), and a group
      that received Internet-based intervention (104). The content of the programs in
      the two intervention groups was the same, emphasizing daily self-weighing and
      self-regulation, as was the frequency of contact with the groups. The primary
      outcome was weight gain over a period of 18 months. RESULTS: The mean (+/-SD)
      weight gain was 2.5+/-6.7 kg in the face-to-face group, 4.7+/-8.6 kg in the
      Internet group, and 4.9+/-6.5 kg in the control group, with a significant
      difference between the face-to-face group and the control group (2.4 kg; 95%
      confidence interval [CI], 0.002 to 10.8; P=0.05). The proportion of participants
      who regained 2.3 kg or more over the 18-month period was significantly higher in
      the control group (72.4%) than in the face-to-face group (45.7%; absolute
      difference, 27%; 95% CI, 14 to 39; P<0.001) or the Internet group (54.8%;
      absolute difference, 18%; 95% CI, 5 to 30; P=0.008). Daily self-weighing
      increased in both intervention groups and was associated with a decreased risk of
      regaining 2.3 kg or more (P<0.001). CONCLUSIONS: As compared with receiving
      quarterly newsletters, a self-regulation program based on daily weighing improved
      maintenance of weight loss, particularly when delivered face to face.
      (ClinicalTrials.gov number, NCT00067145 [ClinicalTrials.gov].)

PMID- 17035650
TI  - Chronic health conditions in adult survivors of childhood cancer.
AB  - BACKGROUND: Only a few small studies have assessed the long-term morbidity that
      follows the treatment of childhood cancer. We determined the incidence and
      severity of chronic health conditions in adult survivors. METHODS: The Childhood
      Cancer Survivor Study is a retrospective cohort study that tracks the health
      status of adults who received a diagnosis of childhood cancer between 1970 and
      1986 and compares the results with those of siblings. We calculated the
      frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A
      severity score (grades 1 through 4, ranging from mild to life-threatening or
      disabling) was assigned to each condition. Cox proportional-hazards models were
      used to estimate hazard ratios, reported as relative risks and 95% confidence
      intervals (CIs), for a chronic condition. RESULTS: Survivors and siblings had
      mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to
      56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had
      at least one chronic condition; 27.5% had a severe or life-threatening condition
      (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor,
      as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life
      threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors,
      the cumulative incidence of a chronic health condition reached 73.4% (95% CI,
      69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of
      42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening
      conditions or death due to a chronic condition. CONCLUSIONS: Survivors of
      childhood cancer have a high rate of illness owing to chronic health conditions.

PMID- 17035651
TI  - External-beam radiotherapy for localized prostate cancer.

PMID- 17035652
TI  - Images in clinical medicine. Medical mystery--visual-field defect.

PMID- 17035653
TI  - Case records of the Massachusetts General Hospital. Case 31-2006. A 15-year-old
      girl with severe obesity.

PMID- 17035654
TI  - Alzheimer's disease--clinical trials and the logic of clinical purpose.

PMID- 17035655
TI  - Rapid detection of tuberculosis and drug-resistant tuberculosis.

PMID- 17035656
TI  - Amyotrophic lateral sclerosis--are microglia killing motor neurons?

PMID- 17035657
TI  - Doxycycline for the prevention of tick-borne relapsing fever.

PMID- 17035658
TI  - The underrecognized burden of influenza.

PMID- 17035659
TI  - Hospital volume and outcomes of mechanical ventilation.

PMID- 17035660
TI  - Intensive care of patients with HIV infection.

PMID- 17035661
TI  - Long-term raloxifene in a woman at high risk for breast cancer.

PMID- 17035662
TI  - Roadmap or roadkill: a pharmacologist's analysis of the NIH Molecular Libraries
      Initiative.

PMID- 17035663
TI  - Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible
      new twist on smallpox therapy.
AB  - Smallpox is a serious and highly contagious disease that is caused by the variola
      virus. It is one of the most severe infectious human diseases known, with
      mortality rates as high as 30%. A successful worldwide vaccination program led to
      the eradication of smallpox in 1980. However, the high transmission rate of
      variola virus, coupled with the deadly nature of smallpox, makes this virus a
      potentially devastating weapon for bioterrorism. Currently, there is no specific
      treatment for smallpox. However, a recent article on the structure of a variola
      topoisomerase IB-DNA complex provides an intriguing starting point for the
      rational design of drugs with potential activity against smallpox.

PMID- 17035664
TI  - Prospects for an anti-ghrelin vaccine to treat obesity.
AB  - In the battle to treat the pandemic of obesity, one therapeutic strategy is to
      block endogenous signals that stimulate appetite and control body weight. One
      such molecule is ghrelin, a gut peptide that is the only known orexigenic hormone
      and is a likely contributor to mealtime hunger. The relative importance of
      ghrelin in long-term body-weight regulation (and thus its promise as an anti
      obesity target) is uncertain, however, because genetic and pharmacologic blockade
      of ghrelin signaling have yielded variable results to date. Using a novel
      approach of vaccinating rats against their own ghrelin, Zorilla et al. report
      that animals with high ghrelin-specific antibody titers displayed restricted body
      weight, without evidence of non-specific inflammation following the vaccine.
      These results favor a meaningful role for ghrelin in energy homeostasis, hinting
      at a possible new anti-obesity approach. More broadly, the work of Zorilla et al.
      supports the feasibility of vaccinations directed against specific autologous
      targets--immunopharmacotherapy that could potentially be developed to target a
      wide array of medical conditions.

PMID- 17035665
TI  - Immunodeficiency is a tough nut to CRAC: the importance of calcium flux in T cell
      activation.
AB  - Severe Combined Immunodeficiency (SCID) is a rare primary immunodeficiency
      disease often characterized by a block in T cell development, which may also
      affect the normal development of B cells and NK cells. Several different
      mutations are known to give rise to SCID, and multiple genes are involved.
      Consequently, there are several different forms of SCID, which can be classified
      according to the metabolic and cellular defects that impede normal lymphocyte
      function. The two most prevalent forms of SCID are X-linked SCID and adenosine
      deaminase (ADA) deficiency SCID, together accounting for approximately 70-80% of
      disease cases. Other genetic abnormalities associated with this syndrome range
      from defective T cell receptor rearrangement to non-functional signaling
      molecules. Recently, a new genetic defect has been described in which mutations
      in a key component of Ca(2+) release activated-channels (CRAC) result in T
      lymphocyte malfunction.

PMID- 17035666
TI  - Salvinorin A: from natural product to human therapeutics.
AB  - The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the
      Sage family that has been used for divination and shamanism by the Mazatecs. Over
      the past decade or so, S. divinorum has been increasingly used recreationally.
      The neoclerodane diterpene salvinorin A is the active component of S. divinorum,
      and recently, the kappa opioid receptor (KOR) has been identified, in vitro and
      in vivo, as its molecular target. The discovery of KOR as the molecular target of
      salvinorin A has opened up many opportunities for drug discovery and drug
      development for a number of psychiatric and non-psychiatric disorders.

PMID- 17035667
TI  - SAR by NMR: putting the pieces together.
AB  - It has been nearly ten years since the introduction of SAR by NMR and the advent
      of fragment-based drug design. During this time, we have gained a tremendous
      amount of knowledge about protein druggability, the limits of chemical diversity,
      and crafting high-affinity ligands from low molecular weight, weakly binding
      leads. This review will describe the concept of fragment-based drug design,
      discuss why it works, and illustrate the power of the approach with two case
      studies on the design of potent inhibitors of matrix metalloproteinases and Bcl-2
      family proteins.

PMID- 17035668
TI  - Measuring the reinforcing strength of abused drugs.
AB  - Animal models for human diseases are highly valued for their utility in
      developing new therapies. Animals have long provided suitable platforms for the
      development of innovative surgical procedures and for the study of disease states
      that are relatively easy to produce in otherwise healthy animals, such as
      diabetes or hypertension. Increasingly, new strains of animals susceptible to
      common human illnesses are being introduced into medical research, promising new
      inroads into the treatment of a variety of organic disorders. Despite these
      advances in model development, psychiatric disorders, by and large, remain among
      the hardest to induce experimentally, and the search for reasonable animal
      procedures to study diseases of the mind is an ongoing challenge for experimental
      biologists. An exception to this limitation, however, comes in the study of drug
      abuse. Major developments in this area of research over the last several decades
      have steadily advanced our ability to identify pharmacological, genetic, and
      environmental determinants that contribute to the development of drug dependence
      and addictive behavior.

PMID- 17035669
TI  - Antimicrobial mouthrinses and the management of periodontal diseases.
      Introduction to the supplement.
AB  - BACKGROUND: Periodontal diseases are complex disorders that have been associated
      with multiple risk factors. These disorders are triggered by the accumulation of
      dental plaque, and the clinical signs are caused by the resultant inflammatory
      and immune responses. Tissue destruction that defines periodontitis has been
      linked to excessive production of proinflammatory molecules including matrix
      metalloproteinases, interleukin-1 beta and prostaglandin E(2). Important risk
      factors for periodontitis can be grouped into four categories: microbial,
      systemic, behavioral and local. These risk factors can be considered modifiable
      or unmodifiable. Controlling risk factors is important in the management of
      chronic diseases and is a valid strategy for controlling periodontal diseases.
      Limiting the accumulation of dental plaque is an important part of controlling
      the development and progression of periodontal diseases. By adhering to a daily
      oral hygiene regimen that includes brushing, flossing and rinsing, patients play
      an essential role in disease management. CONCLUSION: Patients play an important
      role in controlling the oral microbial biofilm that is essential to the
      initiation, development and progression of periodontal diseases. A daily oral
      hygiene regimen that includes the use of an antimicrobial mouthrinse can modify
      patients' microbial risk of developing periodontal disease. CLINICAL
      IMPLICATIONS: Patients can help reduce their risk of developing periodontal
      disease by controlling the accumulation of plaque. This can be accomplished, in
      part, by adhering to a daily oral hygiene regimen that includes brushing,
      flossing and using an antimicrobial mouthrinse.

PMID- 17035670
TI  - Managing the complexity of a dynamic biofilm.
AB  - BACKGROUND: This article provides an overview of the history of oral
      microbiology, a discussion of dental plaque as both a microbial community and a
      biofilm, and a review of the measures available to control the oral microflora.
      TYPES OF STUDIES REVIEWED: The authors reviewed the literature related to oral
      microbiology and associated infectious diseases. They also examined articles that
      detailed the structure and physiology of biofilms, including dental plaque
      biofilms. CONCLUSIONS: Biofilms cannot be eliminated. The pathogenic nature of
      the dental plaque biofilm can be diminished in the oral cavity by reducing the
      bioburden and effectively maintaining a normal oral flora via oral hygiene
      procedures that include daily toothbrushing, flossing and rinsing with an
      antimicrobial mouthrinse. An oral hygiene regimen that includes rinsing with an
      antimicrobial mouthrinse is a practical approach to the prevention and management
      of periodontal diseases. This strategy may have wider benefits when the link
      between periodontal disease and certain systemic diseases is considered. CLINICAL
      IMPLICATIONS: An effective oral hygiene regimen can help control dental plaque
      biofilm and associated periodontal diseases.

PMID- 17035671
TI  - The rationale for the daily use of an antimicrobial mouthrinse.
AB  - BACKGROUND: This article reviews the rationale for incorporating effective
      antimicrobial mouthrinses into a daily oral hygiene regimen along with mechanical
      plaque control methods. TYPES OF STUDIES REVIEWED: The author reviewed studies
      demonstrating the essential etiologic role of a pathogenic dental plaque biofilm
      in the development of gingivitis, as well as studies indicating that most people
      fail to maintain a level of mechanical plaque control sufficient to prevent
      disease. In addition, he did a brief review of studies of oral microbial ecology
      that identified the oral mucosal tissues as a reservoir of bacteria that colonize
      tooth surfaces, and he summarized six-month clinical studies of marketed
      antimicrobial mouthrinse ingredients and products. CONCLUSIONS: There is a
      twofold rationale for daily use of antimicrobial mouthrinses: first, given the
      inadequacy of mechanical plaque control by the majority of people, as a component
      added to oral hygiene regimens for the control and prevention of periodontal
      diseases; second, as a method of delivering antimicrobial agents to mucosal sites
      throughout the mouth that harbor pathogenic bacteria capable of recolonizing
      supragingival and subgingival tooth surfaces, thereby providing a complementary
      mechanism of plaque control. The efficacy of several mouthrinse ingredients and
      products is supported by published six-month clinical trials. CLINICAL
      IMPLICATIONS: The daily use of an effective antiplaque/antigingivitis
      antimicrobial mouthrinse is well-supported by a scientific rationale and can be a
      valuable component of oral hygiene regimens.

PMID- 17035673
TI  - Risk assessment and management of periodontal disease.
AB  - BACKGROUND: As our understanding of periodontal diseases has increased, it has
      become clear that certain risk factors are associated with the diseases'
      incidence, severity and progression. This article focuses on the role of risk
      assessment and disease management in improving patient outcomes, both in the
      general population and in specific population groups with an increased risk of
      developing periodontal disease or with associated comorbidities. TYPES OF STUDIES
      REVIEWED: The author reviewed literature related to the efficacy of risk
      assessment and periodontal disease management in improving clinical outcomes. In
      addition, he examined studies demonstrating a link between periodontal disease
      and specific patient populations and other comorbidities. CONCLUSIONS: Risk
      assessment can help predict a patient's risk of developing periodontal disease
      and improve clinical decision making. In turn, patient adherence to a self-care
      oral health regimen is a key component to successful periodontal disease
      management. CLINICAL IMPLICATIONS: The clinical practice of risk assessment may
      reduce the need for complex periodontal therapy, improve patient outcomes and
      ultimately reduce oral health care costs. Patients are encouraged to become
      actively involved in periodontal disease management by following a daily three
      step regimen of brushing, flossing and rinsing with an antimicrobial mouthrinse.

PMID- 17035672
TI  - Antimicrobial mouthrinse as part of a comprehensive oral care regimen. Safety and
      compliance factors.
AB  - BACKGROUND: Antimicrobial mouthrinses often are used as part of daily oral care
      to reduce plaque and gingivitis. Although several safety factors have been
      associated with long-term use of alcohol-containing mouthrinses, numerous studies
      support the safety of these products in daily care. Patient compliance with daily
      rinsing is important for successful outcomes. TYPES OF STUDIES REVIEWED: The
      authors reviewed studies relating to the safety and efficacy of alcohol
      containing mouthrinses, as well as studies indicating that most patients fail to
      comply with oral health care recommendations. The authors also reviewed a
      behavioral change theory and applied it to oral health care. CONCLUSIONS: Alcohol
      containing antimicrobial mouthrinses are safe and effective as part of a daily
      oral care regimen to prevent or minimize periodontal disease. However, many
      patients do not comply with instructions on how to use them. CLINICAL
      IMPLICATIONS: Antimicrobial mouthrinses are safe and effective, and when used in
      conjunction with brushing and flossing, they are an important method of reducing
      plaque and gingivitis. To improve compliance, dental health care professionals
      should adapt oral health care recommendations to fit patients' specific needs.

PMID- 17035674
TI  - A role of lipin in human obesity and insulin resistance: relation to adipocyte
      glucose transport and GLUT4 expression.
AB  - The mouse lipin gene, Lpin1, is important for adipose tissue development and is a
      candidate gene for insulin resistance. Here, we investigate the adipose tissue
      expression levels of the human LPIN1 gene in relation to various clinical
      variables as well as adipocyte function. LPIN1 gene expression was induced at an
      early step in human preadipocyte differentiation in parallel with peroxisome
      proliferator-activated receptor gamma. Lipin mRNA levels were higher in fat cells
      than in adipose tissue segments but showed no difference between subcutaneous and
      omental depots. Moreover, LPIN1 expression levels were reduced in obesity,
      improved following weight reduction in obese subjects, and were downregulated in
      women with the metabolic syndrome. With respect to adipocyte function, adipose
      LPIN1 gene expression was strongly associated with both basal and insulin
      mediated subcutaneous adipocyte glucose transport as well as mRNA levels of
      glucose transporter 4 (GLUT4). We show that body fat accumulation is a major
      regulator of human adipose LPIN1 expression and suggest a role of LPIN1 in human
      preadipocyte as well as mature adipocyte function.

PMID- 17035675
TI  - High frequency of partial SPAST deletions in autosomal dominant hereditary
      spastic paraplegia.
AB  - BACKGROUND: Hereditary spastic paraplegia (HSP) is a genetically heterogeneous
      neurodegenerative disease. The most frequent cause of autosomal dominant HSP is
      mutation of SPAST (SPG4 locus), but additional pedigrees remain mutation negative
      by conventional screening despite linkage to SPG4. OBJECTIVE: To determine the
      frequency of genomic copy number aberrations of SPAST in autosomal dominant HSP.
      METHODS: We developed and validated a multiplex ligation-dependent probe
      amplification assay targeting SPAST and SPG3A, another gene frequently involved
      in autosomal dominant HSP. In a multicenter study we subsequently investigated 65
      index patients with autosomal dominant HSP, all of whom had previously been
      screened negative for SPAST mutations. Independent secondary samples, additional
      family members, and cDNA were analyzed to confirm positive findings. RESULTS:
      Aberrant MLPA profiles were identified in 12 cases (18%). They exclusively affect
      SPAST, represent deletions, segregate with the disease, and are largely pedigree
      specific. Internal SPAST deletions entail expression of correspondingly shortened
      transcripts, which vary in stability. Age at onset in SPAST deletion carriers
      does not differ from that associated with other SPAST mutations. CONCLUSIONS:
      Partial SPAST deletions, but not SPAST amplifications and SPG3A copy number
      aberrations, represent an underestimated cause of autosomal dominant hereditary
      spastic paraplegia. Partial SPAST deletions are likely to act via
      haploinsufficiency.

PMID- 17035676
TI  - Phase II trial of pirfenidone in adults with neurofibromatosis type 1.
AB  - We performed an open-label phase II trial of oral pirfenidone in 24 patients with
      neurofibromatosis type 1 (NF1). Tumors were monitored by three-dimensional MRI.
      At the end of treatment, four patients had a decrease in tumor volume by 15% or
      more, three had tumor progression, and 17 remained stable. Pirfenidone warrants
      further investigation in NF1, which has until now lacked an effective control
      therapy.

PMID- 17035677
TI  - Metabolite profiling in blood plasma.
AB  - Metabolite profiling has been established as a multiparallel strategy for
      relative quantification of a mixture of compounds or compound classes using
      chromatography and universal detection technologies (gas chromatography-mass
      spectrometry [GC-MS], liquid chromatography-MS). Despite its origins dating back
      to the late 1960s, it was only in the 1980s that its use was acknowledged to
      diagnose metabolic disorders in men, especially for rapid screening of inborn
      errors. Even faster electrospray ionization-MS/MS screening methods replaced
      longish chromatographic methods, and method development had stopped despite its
      potential use for other, less imminent diseases such as likelihood assessments of
      type II diabetes mellitus or cardiovascular risk factor evaluation. In addition
      to its diagnostic use, profiling blood samples can be employed to investigate
      specific biochemical responses. The broader scope of analysis outweighs the
      disadvantages by taking compromises in method development and the reduced
      accuracy for specific metabolites. This chapter exemplifies the strategies in
      metabolite profiling by GC-MS. It gives experimental details on basic steps like
      blood plasma withdrawal, storage, protein precipitation, extraction,
      concentration, derivatization, data acquisition, raw data processing, and result
      data tranformation. A major difference to profiling plant tissues is that no
      fractionation step is utilized, enabling the analysis of primary metabolites like
      sugars and amino acids concomitant with lipids such as sterols and free fatty
      acids.

PMID- 17035678
TI  - Nonsupervised construction and application of mass spectral and retention time
      index libraries from time-of-flight gas chromatography-mass spectrometry
      metabolite profiles.
AB  - Gas chromatography-mass spectrometry (GC-MS) is routinely applied to the
      metabolite profiling of biological samples. Time-of-flight (TOF)-GC-MS metabolite
      profiling is based on highly reproducible electron impact ionization. Single
      chromatograms may comprise 200-1000 mass spectral components. The nature and
      composition of these mass spectral components depend on the choice of metabolite
      extraction, type of biological sample, and experimental condition. The components
      represent mass spectral tags (MSTs) of volatile metabolites or metabolite
      derivatives. Identification of MSTs is the major challenge in GC-MS metabolite
      profiling. We describe methods suitable for the automated construction of mass
      spectral and retention time index databases from large sets of TOF-GC-MS
      profiles. Application of these libraries for automated identification by pure
      reference compounds and classification of hitherto unidentified MSTs from
      biological sources is demonstrated.

PMID- 17035679
TI  - Metabolomic profiling of natural volatiles: headspace trapping: GC-MS.
AB  - Plants are a fabulously rich source of naturally volatile metabolites, which are
      derived from a range of contrasting biochemical pathways (e.g., mono-, di-, and
      sesquiterpenoids, benzoates, alcohols, esters). Such volatiles may immediately be
      released from the plant or they may be stored, e.g., in glycosylated form for
      release later "on demand." Certain roles for these molecules have already been
      determined in that they can function as attractants (e.g., to pollinators, seed
      dispersers, and others) or as protectants (repellants, pathogen inhibitors, and
      so on). The flavor and fragrance of plant materials to humans and other animals
      are also, to a great extent, determined by natural volatiles. Other more
      sophisticated roles have also been elucidated where plant volatiles have been
      shown to be involved either as signal molecules to attract the predators of
      damaging herbivorous insects or potentially even as signal molecules warning
      other plants of imminent danger. As such, detailed knowledge of these components
      can be valuable in relation to breeding crop varieties for enhanced product
      quality or for achieving improved resistance to pathogens and insects.
      Furthermore, knowledge of the metabolites can result in a corresponding knowledge
      of the genes responsible for their synthesis and this can lead to dedicated
      strategies for their in vitro production through, e.g., reverse genetics in
      heterologous microbial expression systems in fermentors for the production of
      high-value fine chemicals. Various analytical techniques based on gas
      chromatography-mass spectrometry have been devised for the analysis of this
      complex group of metabolites. Two of these key methods are detailed in this
      chapter.

PMID- 17035680
TI  - Integrative profiling of metabolites and proteins: improving pattern recognition
      and biomarker selection for systems level approaches.
AB  - Methods such as mRNA expression profiling have provided a vast amount of genomic
      and transcriptomic information about plants and other organisms. However, there
      is explicit indication that considerable metabolic control is executed on the
      metabolite and on the protein level including protein modifications, thereby
      constituting the phenotypic plasticity. Consequently, the analysis of the
      molecular phenotype demands the step toward mass spectrometry (MS)-based
      postgenomic techniques such as metabolomics and proteomics. This chapter
      describes a straightforward protocol for simultaneously extracting metabolites
      and proteins from the same biological sample in preparation for MS analysis.
      Furthermore, protocols for profiling polar metabolites using gas chromatography
      time-of-flight MS and for shotgun proteomics using liquid chromatography-MS are
      discussed. A practical course is laid out that outlines all the basic steps, from
      harvesting to data analysis. These steps enable the correlative study of
      metabolite and protein dynamics with minimal technical variation. Biological
      variability of independent samples is exploited for variance analysis and pattern
      recognition.

PMID- 17035681
TI  - Integrating profiling data: using linear correlation to reveal coregulation of
      transcript and metabolites.
AB  - Recent advances in the medical and biological sciences have been characterized by
      a major paradigm shift from reductionism to integrated and holistic systems
      approaches. Such approaches are characterized at the experimental level by the
      multiparallel analysis of a multitude of parameters of a given biological system
      at a range of different molecular levels, following the systematic perturbation
      of the system in question. Although a multitude of studies have been carried out
      to assess the transcript, protein, and metabolite complements of cells under
      various conditions, to date, few have been attempted that encompass the profiling
      of more than one of these entities. In this chapter, we describe combined
      analysis of data obtained from transcript and metabolic profiling, and detail
      advantages of using both approaches in parallel.

PMID- 17035682
TI  - Visualization and analysis of molecular data.
AB  - This chapter provides an overview of visualization and analysis techniques
      applied to large-scale datasets from genomics, metabolomics, and proteomics. The
      aim is to reduce the number of variables (genes, metabolites, or proteins) by
      extracting a small set of new relevant variables, usually termed components. The
      advantages and disadvantages of the classical principal component analysis (PC A)
      are discussed and a link is given to the closely related singular value
      decomposition and multidimensional scaling. Special emphasis is given to the
      recent trend toward the use of independent component analysis, which aims to
      extract statistically independent components and, therefore, provides usually
      more meaningful components than PCA. We also discuss normalization techniques and
      their influence on the result of different analytical techniques.

PMID- 17035683
TI  - A gentle guide to the analysis of metabolomic data.
AB  - Modern molecular biology crucially relies on computational tools to handle and
      interpret the large amounts of data that are generated by high-throughput
      measurements. To this end, much effort is dedicated to devise novel sophisticated
      methods that allow one to integrate, evaluate, and analyze biological data.
      However, prior to an application of specifically designed methods, simple and
      well-known statistical approaches often provide a more appropriate starting point
      for further analysis. This chapter seeks to describe several well-established
      approaches to data analysis, including various clustering techniques,
      discriminant function analysis, principal component analysis, multidimensional
      scaling, and classification trees. The chapter is accompanied by a webpage,
      describing the application of all algorithms in a ready-to-use format.

PMID- 17035684
TI  - Capillary electrophoresis-mass spectrometry for metabolomics.
AB  - A new approach for the comprehensive and quantitative analysis of charged
      metabolites by capillary electrophoresis-mass spectrometry (CE-MS) is described.
      Metabolites are first separated by CE based on charge and size, and then
      selectively detected using MS by monitoring ions over a large range of m/z
      values. This technique enables the simultaneous determination of over 1000
      charged species, and it can readily be applied to various types of biological
      samples originating from bacteria, plants, mammals, body fluids, and others. This
      chapter highlights detailed practical procedures for using this technology.

PMID- 17035685
TI  - Application of liquid chromatography-mass spectrometry analysis in metabolomics:
      reversed-phase monolithic capillary chromatography and hydrophilic chromatography
      coupled to electrospray ionization-mass spectrometry.
AB  - Analysis of the entire metabolome as the sum of all detectable components in the
      sample rather than analysis of each individual metabolite is performed by the
      metabolomics approaches. To monitor in parallel hundreds or even thousands of
      metabolites, high-throughput techniques are required that enable screening for
      relative changes rather than absolute concentrations of compounds. Most
      analytical techniques for profiling small molecules consist of gas chromatography
      (GC) or high-performance liquid chromatography (HPLC) coupled to mass
      spectrometry. HPLC separations are better suited for the analysis of labile and
      high molecular weight compounds, and for the analysis of nonvolatile polar
      compounds in their natural form. Although GC- and HPLC-based profiling techniques
      are not truly quantitative, the compounds detecting and employing the acceptable
      standards may compare their relative amounts. We have demonstrated that reversed
      phase monolithic capillary chromatography and hydrophilic chromatography can be
      successfully applied for sufficient plant crude extracts separations and
      metabolomics studies.

PMID- 17035686
TI  - High-performance liquid chromatography separations coupled with coulometric
      electrode array detectors: a unique approach to metabolomics.
AB  - Metabolomics is the systematic and theoretically comprehensive study of the small
      molecules that comprise a biological sample, e.g., sera or plasma. The primary
      analytical tools used in metabolomics are nuclear magnetic resonance and mass
      spectroscopy. We here address a different tool, high-performance liquid
      chromatography (HPLC) separations coupled with coulometric electrode array
      detection. This system has unique advantages, notably sensitivity and high
      quantitative precision, but also has unique limitations, such as obtaining little
      structural information on the metabolites of interest and limited scale-up
      capacity. The system also only detects redox-active compounds, which can be
      either a benefit or a detriment, depending on the experimental goals and design.
      Here, we discuss the characteristics of this HPLC/coulometric electrode array
      system in the context of metabolomics, and then present the method as practiced
      in our groups.

PMID- 17035687
TI  - Determination of metabolic flux ratios from 13C-experiments and gas
      chromatography-mass spectrometry data: protocol and principles.
AB  - Network topology is a necessary fundament to understand function and properties
      of microbial reaction networks. A valuable method for experimental elucidation of
      metabolic network topology is metabolic flux ratio analysis, which quantifies the
      relative contribution of two or more converging pathways to a given metabolite.
      It is based on 13C-labeling experiments, gas chromatography-mass spectrometry
      analysis, and probabilistic equations that relate mass distributions in
      proteinogenic amino acids to pathway activity. Here, we describe the protocol for
      sample generation and illustrate the principles underlying the calculation of
      metabolic flux ratios with three examples. These principles are also implemented
      in the publicly available software FiatFlux, which directly calculates flux
      ratios from the mass spectra of amino acids.

PMID- 17035688
TI  - Understanding the roadmap of metabolism by pathway analysis.
AB  - The theoretical investigation of the structure of metabolic systems has recently
      attracted increasing interest. In this chapter, the basic concepts of metabolic
      pathway analysis are described and various applications are outlined. In
      particular, the concepts of nullspace and elementary flux modes are explained.
      The presentation is illustrated by a simple example from tyrosine metabolism and
      a system describing lysine production in Corynebacterium glutamicum. The latter
      system gives rise to 37 elementary modes, 36 of which produce lysine with
      different molar yields. The examples illustrate that metabolic pathway analysis
      is a useful tool for better understanding the complex architecture of
      intracellular metabolism, for determining the pathways on which the molar
      conversion yield of a substrate-product pair under study is maximal, and for
      assigning functions to orphan genes (functional genomics). Moreover, problems
      emerging in the modeling of large networks are discussed. An outlook on current
      trends in the field concludes the chapter.

PMID- 17035689
TI  - Revealing the metabolome of animal tissues using 1H nuclear magnetic resonance
      spectroscopy.
AB  - The measurement of tissue-specific metabolic fingerprints can be of particular
      interest when investigating disease processes, mechanisms of toxicity, or when
      knowledge of the metabolic interactions between different organs is required.
      This chapter presents several optimized protocols for the extraction of
      metabolites from animal tissues, their analysis by 1H nuclear magnetic resonance
      (NMR) spectroscopy, and the subsequent spectral preprocessing required for an NMR
      based metabolomics experiment. First, the three critical steps in the preparation
      of tissue extracts for NMR analysis are described, including both a perchloric
      acid protocol for the extraction of polar metabolites, and a methanol:chloroform
      protocol for extraction of polar and lipophilic metabolites. Then a series of NMR
      experiments are described including a standard one-dimensional (1D) 1H NMR study,
      a 1D 1H Carr-Purcell-Meiboom-Gill spin-echo experiment, and a two-dimensional 1H
      1H J-resolved NMR experiment. The advantages and limitations of each experiment
      for metabolomics research are discussed. Analysis of the resulting NMR datasets
      is typically conducted in two phases comprising "low level" spectral
      preprocessing and "high level" multivariate analysis. NMR spectral preprocessing
      is a critical step that converts raw NMR spectra into an appropriate data format
      for multivariate analysis. A detailed protocol for preprocessing NMR data, using
      ProMetab software, is presented. Because a plethora of algorithms exist for
      multivariate analyses, which can be used to construct classification models or
      for biomarker discovery, this is beyond the scope of the current chapter.

PMID- 17035690
TI  - Nuclear magnetic resonance metabonomics: methods for drug discovery and
      development.
AB  - Nuclear magnetic resonance (NMR)-based metabonomics is gaining popularity in drug
      discovery and development and in academia in a variety of settings, ranging from
      toxicology, preclinical, and clinical approaches to nutrition research, studies
      on microorganisms, and research on plants. This chapter focuses on the basic
      steps in a metabonomics study and emphasizes experience and lessons learned in
      our lab where we focused on metabonomic analyses of plant extracts, cell lines,
      and a variety of animal tissues and biofluids. We emphasize that a comprehensive
      and suitable study design is pivotal for a correct biological interpretation of
      the results, as well as highly controlled experimental conditions. Sample
      preparation and NMR protocols are detailed for a wide range of sample types. We
      discuss alternative data processing strategies and considerations for a general
      data analysis approach, paying particular attention to the statistical
      interpretation and validation of the results while also highlighting approaches
      to avoid possible pitfalls resulting from systematic and random errors. A
      tutorial written for the R statistical package and other small utilities are
      available from the authors upon request.

PMID- 17035691
TI  - Practical aspects of uniform stable isotope labeling of higher plants for
      heteronuclear NMR-based metabolomics.
AB  - Analytical methods for probing plant metabolism are taking on new significance in
      the era of functional genomics, metabolomics, and systems biology. Nuclear
      magnetic resonance (NMR) is becoming a key technology in plant metabolomics.
      Stable isotope labeling of cultured cells and higher organisms has been
      especially promising in that it allows the use of advanced heteronuclear NMR
      methodologies through a combination of in vivo and in vitro measurements. This
      new approach provides much better resolution of the metabolite mixture signals in
      the multidimensional NMR spectra than does the conventional one-dimensional 1H
      NMR previously used in plant metabolomics. In this chapter, we describe the
      practical aspects of two key NMR technologies: uniform stable labeling of plants
      and in vitro heteronuclear NMR.

PMID- 17035692
TI  - Hospital admissions associated with traumatic brain injury in the US Army during
      peacetime: 1990s trends.
AB  - INTRODUCTION: This paper examines 10-year trends in traumatic brain injury (TBI)
      related hospitalization rates for active duty US Army personnel in the 1990s. It
      does this within the context of various factors, including enhanced injury
      prevention policies and changed hospital admission practices, that may have
      affected TBI hospitalization rates. It also compares TBI hospitalization rates in
      the Army to those from an age-comparable segment of the US civilian population
      over this time period. METHODS: Crude (unadjusted) incidence rates for all active
      duty US Army personnel hospitalized with a TBI diagnosis from fiscal years (FY)
      1990 to 1999 were calculated. Once the trends were identified, the percentage
      change in the overall rate, as well as the rates for different TBI severity
      levels, and in-hospital deaths from FY1990 and FY1999 were analyzed. Changes in
      age- and gender-specific rates as well as crude rates for cases with and without
      other injuries and cases treated in military and civilian hospitals were also
      analyzed. Rate ratios were used to compare aggregated 5-year TBI hospitalization
      rates in the Army to rates for civilians 17-49 years of age during the following
      time periods: 1990-1994 and 1995-1999. The rates used in the comparison were
      adjusted to control for differences in age and gender. RESULTS: The overall
      incidence of TBI-related hospitalization in the Army decreased 75% from FY1990 to
      FY1999. The rates for all TBI severity levels decreased, but the rate for mild
      TBI decreased more than the rates for moderate and severe TBI. The rate of in
      hospital deaths from TBI also decreased. Rates decreased similarly for males and
      females, across all age groups, as well as for cases with and without other
      injuries. TBI rates decreased for Army personnel treated in military hospitals
      but changed minimally for Army personnel treated in civilian hospitals. The
      Army's TBI hospitalization rates were generally higher than civilian rates in the
      early 1990s but by the late 1990s, most of the Army's rates were lower than or
      equal to the civilian rates. CONCLUSIONS: The incidence of TBI-related
      hospitalization in the active duty US Army decreased markedly (75%) during the
      1990s. As a result, most of the Army's TBI hospitalization rates were lower than
      civilian rates by the late 1990s. Effective injury prevention and changes in the
      Army population were two of the factors that likely contributed to the decrease
      in rates for all TBI severity levels, while changes in hospital admission
      practices likely contributed to the disproportionate decrease in the Army's rates
      for mild TBI.

PMID- 17035693
TI  - Descriptive epidemiology of spinal muscular atrophy type I in Estonia.
AB  - Spinal muscular atrophy is the second most frequent autosomal-recessive disorder
      in Europeans. There are no published epidemiological data on SMA in Estonia and
      other Baltic countries. The aim of this study was to estimate the incidence of
      SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and
      December 2003 were included in the study. The diagnosis was established on the
      basis of neurological evaluation, ENMG findings, molecular studies and muscle
      biopsy. PCR and restriction enzyme analysis was used to detect the homozygous
      deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during
      this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live
      births, which is similar to the result from Hungary but lower than average
      incidence in the world. Only one of the patients was female. Typical SMN1 gene
      deletion was found in all cases.

PMID- 17035694
TI  - Decision rules guiding the clinical diagnosis of Alzheimer's disease in two
      community-based cohort studies compared to standard practice in a clinic-based
      cohort study.
AB  - We developed prediction rules to guide the clinical diagnosis of Alzheimer's
      disease (AD) in two community-based cohort studies (the Religious Orders Study
      and the Rush Memory and Aging Project). The rules were implemented without
      informant interviews, neuroimaging, blood work or routine case conferencing.
      Autopsies were performed at death and the pathologic diagnosis of AD made with a
      modified version of the Consortium to Establish a Registry for Alzheimer's
      Disease (CERAD) criteria. We compared the positive predictive value of the
      clinical diagnosis in the two community-based studies to the positive predictive
      value of the clinical diagnosis of AD made by standard clinical practice in a
      clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic
      cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD;
      the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141
      study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria
      for AD; the results were lower but acceptable for those with possible AD (26 of
      37, 70.3%). The results were similar in secondary analyses using alternate
      neuropathologic criteria for AD. The clinical diagnosis of AD can be made in
      community-based studies without the use of informant interviews, neuroimaging,
      blood work or routine case conferencing. This approach holds promise for reducing
      the operational costs of epidemiologic studies of aging and AD.

PMID- 17035695
TI  - 'The success of the mentee is the mentor's ultimate reward'. An interview with
      Dr. Michael L. Steer by Martin E. Fernandez-Zapico.
AB  - In this interview, Dr. Michael Steer shares his life experience in pancreatic
      research, discusses the importance of mentorship and gives advice to young
      investigators starting in this field. Dr. Michael Steer is a world-renown
      investigator who has made an extraordinary contribution to the understanding of
      pancreatic physiology. His achievements in the field of acute pancreatitis were
      the foundation for the characterization of the cellular basis for this disease.

PMID- 17035698
TI  - Report of the 15th European Stroke Conference, Brussels, May 16-19, 2006.

PMID- 17035697
TI  - A randomized controlled trial of oral versus intravenous iron in chronic kidney
      disease.
AB  - BACKGROUND: It is unknown whether intravenous iron or oral iron repletion alone
      can correct anemia associated with chronic kidney disease (CKD). We conducted a
      randomized multicenter controlled trial in adult anemic, iron-deficient non
      dialysis CKD (ND-CKD) patients (>or=stage 3) not receiving erythropoiesis
      stimulating agents (ESAs). METHODS: The participants were randomized to receive
      either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly x
      4 or ferrous sulfate (oral iron) 325 mg t.i.d. x 42 days. Hemoglobin (Hgb),
      ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney
      Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43.
      The primary outcome variable was change from baseline (CFB) to endpoint in Hgb
      values. RESULTS: Seventy-five patients were analyzed (intravenous iron n = 36,
      oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4
      g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only
      significant with intravenous iron (p < 0.01). In comparison to oral iron,
      intravenous iron achieved greater improvements in ferritin (232.0 +/- 160.8 vs.
      55.9 +/- 236.2 ng/ml, p < 0.001) and TSAT (8.3 +/- 7.5 vs. 2.9 +/- 8.8%, p =
      0.007). Intravenous iron caused greater improvements in KDQoL scores than oral
      iron (p < 0.05). The most common side effect reported with intravenous iron was
      hypotension, while constipation was more common with oral iron. CONCLUSIONS: Oral
      and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD
      patients not receiving ESAs. Although in comparison to oral iron, intravenous
      iron may result in a more rapid repletion of iron stores and greater improvement
      in quality of life, it exposes the patients to a greater risk of adverse effects
      and increases inconvenience and cost.

PMID- 17035699
TI  - Surgical shunt closure via the lumen of an intrahepatic portal aneurysm.
AB  - BACKGROUND/AIMS: A surgical shunt closure via the lumen of an intrahepatic portal
      aneurysm was successfully performed in a 70-year-old Japanese woman with hepatic
      encephalopathy due to hyperammonemia. She had a 4-month history of repeated
      hepatic encephalopathy which persisted after treatment with oral medicine. Color
      Doppler ultrasonography and computed tomography revealed a cystic peripheral
      portal aneurysm, 4 cm in diameter, connecting the posterior branch of the portal
      vein to the short hepatic vein in the right lobe. METHODS: While performing the
      Pringle maneuver and clamping the inferior vena cava below the liver, the wall of
      the portal aneurysm was opened, and the site of inflow from the portal vein and
      the site of outflow to the hepatic vein via the lumen of the portal aneurysm were
      closed with interrupted sutures. RESULTS: The patient's postoperative course was
      uneventful, and she was discharged 12 days after surgery. 12 months after
      surgery, she had no recurrence of hyperammonemia or hepatic encephalopathy.
      CONCLUSION: Surgical shunt closure via the lumen of a portal aneurysm can be
      performed safely, easily, and completely with good vision.

PMID- 17035700
TI  - Ectopic pancreas in the ampulla of vater with obstructive jaundice. A case report
      and review of literature.
AB  - Ectopic pancreas is an uncommon condition and is usually found in the
      gastrointestinal tract, such as stomach, duodenum and jejunum. However, ectopic
      pancreas in the ampulla of Vater is rare and its clinical presentations may be
      similar to periampullary cancer. It is difficult to diagnose preoperatively. We
      present such a case where the diagnosis was proven postoperatively. Our patient,
      a 51-year-old man, presented with epigastric pain, jaundice, weight loss and
      abnormal laboratory data. Imaging study, including abdominal sonography,
      abdominal computerized tomography with contrast and endoscopic retrograde
      cholangiopancreatography, showed a mass protruding into the ampulla of Vater. The
      mass was resected and histological examination revealed an ectopic pancreas. The
      patient presented with symptoms of periampullary tumor but the imaging study did
      not reveal an obvious lesion for us consider the possibility of ectopic pancreas.
      Surgical excision is indicated for symptomatic cases.

PMID- 17035701
TI  - Digestive tract schwannoma.
AB  - BACKGROUND: Digestive tract schwannomas (DTS) are rare benign mesenchymal tumours
      usually affecting females between 30 and 60 years old. METHODS: We
      retrospectively reviewed 2 cases of DTS treated at our hospital. The first case
      is a 38-year-old female with gastric schwannoma presenting with acute upper
      gastro-intestinal bleeding. The second case is a 36-year-old female with
      mesenteric schwannoma presenting with chronic right iliac fossa pain. Both
      patients underwent surgical resection of the tumour. RESULTS: Histology and
      immunohistochemistry revealed the typical appearance of a DTS. CONCLUSION: DTS is
      most commonly found in the stomach. It is usually asymptomatic but can present
      with variable symptoms. Definitive diagnosis can only be made on the basis of
      immunohistochemistry. Surgical resection is the treatment of choice.

PMID- 17035702
TI  - Asymptomatic carotid artery stenosis: past, present and future. How to improve
      patient selection?
AB  - BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid
      artery stenosis (aCAS) remains a matter of debate. It seems that not only the
      degree of stenosis, but also other factors have to be taken in account to improve
      patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS:
      The literature pertaining aCAS was reviewed in order to describe the natural
      history, risk of stroke and benefit of CEA for patients with aCAS in regard to
      several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors
      influencing the indication for CEA are severity of stenosis, age, contralateral
      disease, stenosis progression to >80%, gender, concomitant operations and life
      expectancy. To improve patient selection investigations will concentrate on
      plaque characteristics and instability and cerebral hemodynamics and metabolism.

PMID- 17035704
TI  - Anesthesia dolorosa caused by penetrating cranial injury.
AB  - Anesthesia dolorosa (AD) is an uncommon complication of surgical treatments for
      trigeminal neuralgia. Its incidence is around 0.8%. To our best knowledge, AD
      caused by a penetrating cranial injury has not been reported previously. We
      report the case of a 31-year-old male patient with left-sided neuropathic
      keratitis and AD that began 18 years earlier, following a penetrating cranial
      injury with a knife to the left postauricular area. The patient was successfully
      treated by a carbamazepine and gabapentin combination. In conclusion, penetrating
      cranial injury is uncommon but may cause a serious neurologic disturbance. In the
      differential diagnosis of AD, a penetrating injury should be kept in mind. In
      these cases, treatments should be effective and immediate; otherwise, this may
      result in catastrophic consequences such as neurotrophic keratitis and blindness.
      Ophthalmologists should be aware of these potential problems.

PMID- 17035703
TI  - Longitudinal study of bone and calcium metabolism and fracture incidence in
      spinocerebellar degeneration.
AB  - Little is known about bone and calcium metabolism and fracture incidence in
      spinocerebellar degeneration (SCD) despite frequent falls and immobilization. To
      address bone and calcium metabolism and fracture incidence in SCD, we conducted a
      10-year prospective study in a cohort of adult patients with SCD. Bone mineral
      density (BMD) and serum levels of ionized calcium, parathyroid hormone, 25
      hydroxyvitamin D, and pyridinoline cross-linked carboxy-terminal telopeptide of
      type I collagen (ICTP) were followed in 110 patients with SCD for 10 years. Age
      matched healthy volunteers (n = 110) served as controls. At baseline, the SCD
      patients had a low BMD with high levels of serum ionized calcium and ICTP which
      correlated with the degree of immobilization (Barthel index). Over 10 years,
      serum 25-hydroxyvitamin D decreased to the osteomalacic level (<5 ng/ml), and
      calcium and ICTP further increased in accordance with a decreased Barthel index
      score. The BMD decreased by 15.2% in men and by 24.6% in women. The incidence of
      fractures in the patients was significantly higher as compared with the control
      group (men 8/49 vs. 1/42, p = 0.0428; women 16/49 vs. 2/48, p = 0.0026). Over 10
      years, the BMD was significantly reduced in the SCD patients, particularly in
      women, which increased the risk of a fracture. Vitamin D deficiency due to
      sunlight deprivation, increased bone resorption due to immobilization, and
      frequent falls are probable causes of osteoporosis and fractures in these
      patients. Hypovitaminosis D and increased bone resorption may be corrected
      readily by the routine use of vitamin D supplements together with bisphosphonate.

PMID- 17035705
TI  - Early pathological changes in the cerebellum of patients with pure cerebellar
      syndrome demonstrated by diffusion-tensor imaging.
AB  - We evaluated the early pathological changes in patients with sporadic cerebellar
      ataxia by measuring fractional anisotropy (FA) values in diffusion tensor MRIs
      (DTI). FA and apparent diffusion coefficient (ADC) values were compared in the
      brain stem and cerebellum of 5 patients with idiopathic cerebellar ataxia-C and 7
      age-matched controls. Patients with sporadic cerebellar ataxia had decreased FA
      values in the bilateral cerebellar peduncle and cerebellar hemisphere, but normal
      FA values in the basis pontes. Assuming that the loss in FA parallels neuronal
      changes, our results suggest that the derangement and altered fiber integrity of
      the cerebellum are present regardless of the presence of morphological
      alterations on conventional MRI. Therefore, DTI may be superior to conventional
      MRI in the evaluation of early pathological changes in patients with sporadic
      cerebellar ataxia.

PMID- 17035706
TI  - Inclusion body myopathy-like changes in a family with cerebellar atrophy, mental
      retardation and abnormal pupils.

PMID- 17035707
TI  - Images in clinical medicine: miliary tuberculosis of the brain.

PMID- 17035708
TI  - Neurological words. Nosology, nosocomial.

PMID- 17035709
TI  - F344 rat liver nonparenchymal cell transplantation can increase the number of
      albumin-positive hepatocytes in the liver following hematopoietic reconstitution
      in irradiated analbuminemic rats.
AB  - The adult liver contains hematopoietic stem cells that can reconstitute the bone
      marrow. We tested whether bone marrow cells (BMCs) derived from liver
      nonparenchymal cells (LNPCs) can increase the number of hepatocytes within
      livers. LNPCs from Fischer 344 rats (F344) were infused into the penile veins of
      F344 congenic Nagase's analbuminenic rats (F344alb) immediately after whole-body
      irradiation, and the recipients were sacrificed 8 weeks later. Eleven of 15
      (73.3%) F344alb that received the LNPC transplantation after irradiation
      survived, while only 1 of 8 (12.5%) F344alb that received irradiation alone was
      alive after 8 weeks. Normal albumin gene sequences were detected by PCR in BMCs
      of the recipient F344alb that received LNPC transplantation after irradiation,
      indicating that F344alb bone marrow was reconstituted by F344 LNPCs. Although
      single or pairs of albumin-positive (Alb+) hepatocytes were seen in the liver of
      untreated F344alb and those with irradiation or LNPC transplantation alone,
      clusters consisting of >3 Alb+ hepatocytes were detected in the livers of F344alb
      with the LNPC or BMC transplantation after irradiation together with single or
      double Alb+ cells. Normal albumin gene sequences were detected by PCR in the DNA
      isolated from such Alb+ hepatocyte clusters microdissected from the immunostained
      sections. The data indicate that BMCs derived from F344 LNPCs could increase the
      number Alb+ hepatocytes within the F344alb liver.

PMID- 17035710
TI  - Association of physical activity and the metabolic syndrome in children and
      adolescents: CASPIAN Study.
AB  - BACKGROUND/AIM: To determine the association of physical activity and the
      metabolic syndrome in a large national-representative sample of children.
      METHODS: This study was performed in 2003-2004 on 4,811 school students aged 6-18
      years, selected by multi-stage random cluster sampling from six provinces in
      Iran. We assessed the level of physical activity using a standardized
      questionnaire, and categorized it to the tertiles. The metabolic syndrome was
      defined based on criteria analogous to those of the Adult Treatment Panel III.
      RESULTS: The participants comprised 2,248 boys and 2,563 girls with a mean age of
      12.07 +/- 3.2 years. In all age groups, boys were more physically active than
      girls. The metabolic syndrome was detected in 14.1% of participants, and its
      prevalence was higher in those subjects in the 1st, 2nd and 3rd tertiles of
      physical activity, respectively (15.1 vs.14.2 and 13.1%, respectively, p <0.05).
      This difference was seen in boys, while no difference was found between girls in
      the 2nd and 3rd tertiles of physical activity. Physical activity was linked to a
      cluster of factors consisting of high-density lipoprotein-cholesterol and waist
      circumference, followed by triglycerides in boys, and of triglycerides, waist
      circumference and blood pressure in girls. In both genders, before and after
      adjustment for age and body mass index, low levels of physical activity
      significantly increased the risk of having the metabolic syndrome [in boys: OR:
      1.8, 95% CI: 1.1, 2.1; and in girls, OR: 1.6 (1.1, 1.9)]. CONCLUSION: We found an
      association between physical activity and the metabolic syndrome, which was
      independent of body mass index and age. Children should be encouraged to have
      greater physical activity.

PMID- 17035711
TI  - Rate of decline of GFR and progression of vascular disease in type 2 diabetic
      patients with diabetic or vascular nephropathy during the last three years before
      starting dialysis therapy.
AB  - BACKGROUND: The progression of chronic renal insufficiency depends on the type of
      primary renal disease and blood pressure (BP) levels. We investigated the rate of
      decline of glomerular filtration rate (GFR) during 3 years prior to the start of
      dialysis therapy in type 2 diabetic patients with diabetic nephropathy (dNP) or
      vascular nephropathy (vNP). The aim of the study was to determine differences in
      the progression of renal insufficiency and the prevalence of vascular diseases in
      the two patient groups. METHODS: In a retrospective study, we investigated type 2
      diabetic patients with chronic renal insufficiency who were undergoing regular
      controls in our outpatient care unit for at least 3 years prior to the start of
      dialysis. We evaluated only patients who had already died under chronic dialysis
      therapy, and whose diagnosis of primary renal disease was histologically
      conformed at autopsy. A total of 40 type 2 diabetic patients were included in the
      study. Of these, 28 patients had dNP (age 62 +/- 8 years) and 12 had vNP (age 70
      +/- 7 years). The following parameters were determined at 3- to 6-month
      intervals: body weight, BP, HbA1c, serum creatinine (Cr), Cr clearance (Cockroft
      formula), cholesterol and triglycerides. The prevalence of vascular disease in
      the two groups was also assessed. RESULTS: The average decrease in Cr clearance
      was 7.7 +/- 2.4 ml/min/year in patients with dNP and 7.7 +/- 2.1 ml/min/year in
      those with vNP (NS). During the entire observation period, mean HbA1c values (7.0
      +/- 0.8 vs. 6.8 +/- 0.6%), systolic BP (137 +/- 8 vs. 138 +/- 11 mm Hg) and
      diastolic BP (86 +/- 4 vs. 87 +/- 7 mm Hg), cholesterol and triglycerides did not
      differ significantly in the two groups. The prevalence of vascular disease 3
      years prior to and at the start of dialysis therapy was similar in patients with
      dNP and vNP. CONCLUSION: The progression of dNP and vNP is similar at least
      during 3 years before the start of dialysis therapy. Vascular risk factors and
      the prevalence of vascular diseases were not significantly different in the two
      patient groups. However, diabetic patients with ESRD secondary to dNP were
      significantly younger than those with vNP.

PMID- 17035712
TI  - Is 44-hour better than 24-hour ambulatory blood pressure monitoring in
      hemodialysis?
AB  - The aim of this study is to evaluate if hemodialysis (HD) patients with similar
      blood pressure (BP) in the whole inter-HD period could have different target
      organ lesions and survival if the behavior of BP differs from the first to the
      second day of the inter-HD period. The present study compares 44-hour ambulatory
      BP monitoring (ABPM) patterns in 45 HD patients. Three BP patterns emerged: group
      A (n = 15) had similar BPs throughout (138 +/- 11/88 +/- 12 in the first 22 h vs.
      140 +/- 11/87 +/- 12 mm Hg in the second 22-hour period); group B (n = 15) had a
      significant systolic BP rise from the first to the second period (132 +/- 15/80
      +/- 12 vs. 147 +/- 12/86 +/- 13 mm Hg, p < 0.05); group C (n = 15) had
      significantly higher BPs (p < 0.05) than the other 2 groups throughout the whole
      inter-HD period, with no significant change between the 2 halves (172 +/- 14/108
      +/- 12 vs. 173 +/- 18/109 +/- 14 mm Hg). Ventricular mass and survival during the
      30-month follow-up period were statistically significantly better in group A,
      intermediate in group B and worse in group C. The data suggest that a 44-hour
      ABPM is more accurate than a 24-hour one in evaluating organ lesion and prognosis
      in HD patients.

PMID- 17035713
TI  - Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in
      ifosfamide nephropathy.
AB  - Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO)
      and putatively responsible for renal damage following anti-tumor therapy with
      IFO. Depletion of sulfhydryl (SH) groups has been reported from cell culture,
      animal and clinical studies. In this work the effect of CAA on human proximal
      tubule cells in primary culture (hRPTEC) was investigated. Toxicity of CAA was
      determined by protein content, cell number, LDH release, trypan blue exclusion
      assay and caspase-3 activity. Free thiols were measured by the method of Ellman.
      CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular
      thiols and an increase in necrosis markers. CAA but not acrolein inhibited the
      cysteine proteases caspase-3, caspase-8 and cathepsin B. Caspase activation by
      cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting
      lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The
      effects of CAA on cysteine protease activities and thiols could be reproduced in
      cell lysate. Acidification, which slowed the reaction of CAA with thiol donors,
      could also attenuate effects of CAA on necrosis markers, thiol depletion and
      cysteine protease inhibition in living cells. Thus, CAA directly reacts with
      cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. This
      effect can be reduced by acidification. Therefore, urinary acidification could be
      an option to prevent IFO nephropathy in patients.

PMID- 17035715
TI  - Tutorial in biostatistics: Analyzing associations between total plasma
      homocysteine and B vitamins using optimal categorization and segmented
      regression.
AB  - Data analysts consider standard regression models (e.g., generalized linear
      model) or nonparametric smoothing techniques (e.g., loess or splines) when
      examining the association between two variables. Before this step, a quantile
      based summarization is typically used for exploring the exposure-response
      relationship. Unfortunately, these exploratory approaches may not be optimal or
      efficient for guiding the formal analysis in many biological and nutritional data
      settings. We suggest a recently developed method for selection of cutpoints as a
      tool of data summary and segmented regression as a modeling approach in the
      analysis of plasma total homocysteine and related vitamins. These methods are
      often complementary in discovering the underlying complex pattern of association.

PMID- 17035714
TI  - Socio-demographic variation of dementia subtypes in china: Methodology and
      results of a prevalence study in Beijing, Chengdu, Shanghai, and Xian.
AB  - OBJECTIVE: To characterize sociodemographic variations in the prevalence of AD
      and VaD in China. METHODS: Data were collected in a 1997-1998, cross-sectional,
      door-to-door prevalence survey of 34,807 community residents ages > or =55 years
      in Beijing, Shanghai, Chengdu and Xian. Initial diagnoses of AD and VaD were
      assessed by clinicians using standardized protocols, according to the NINCDS
      ADRDA and NINDS-AIREN criteria; diagnoses were confirmed after 6 months by
      repeating neuropsychological evaluations. Prevalence odds ratios were estimated
      in logistic models adjusting for survey design, age, and other sociodemographic
      factors. RESULTS: We identified 732 prevalent cases of AD and 295 cases of VaD.
      Adjusting for all sociodemographic factors concurrently, prevalence odds of AD
      and VaD were higher in northern versus southern China. Age trends for AD appeared
      different in western and eastern China. AD also showed an age-adjusted elevation
      among women and, in the fully adjusted model, a gender education interaction
      indicating a female preponderance in the highest education group. North-south
      variation for VaD was age-dependent. In the fully adjusted model, for AD, widowed
      had significantly higher prevalence odds; for VaD, widowed persons and minorities
      had significantly lower prevalence odds; professionals had statistically
      significant and borderline lower prevalence odds for both VaD and AD; sales
      service occupations had significantly lower odds for AD only. CONCLUSION: We
      observed variations in prevalence for AD and VaD in different regions and
      demographic groups in China that persisted after controlling for potential
      confounding factors. Sociodemographic factors are probable surrogates for
      conditions such as lifestyle, environment, comorbidities, and life expectancy.

PMID- 17035716
TI  - Induction of apoptosis in HaCaT cells by photodynamic therapy with chlorin e6 or
      pheophorbide a.
AB  - The two photosensitizers, chlorin e6 and pheophorbide a, were tested in an in
      vitro model of topical photodynamic therapy (PDT). Both dyes accumulate in HaCaT
      keratinocytes as verified by fluorescence measurement but pheophorbide a is
      enriched fivefold more strongly than chlorin e6 after 24 h. HaCaT cells are
      susceptible to PDT with both dyes. The phototoxicity measured by ATP
      bioluminescence is caused by necrosis and apoptosis depending on the
      photosensitizer used and the treatment modality. Chlorin e6 shows higher toxic
      potential because it elicits nearly 90% cell mortality 24 h after PDT comparable
      to pheophorbide a but with a fivefold lower rate of accumulation. These results
      implicate caution with topical PDT of oncologic diseases due to the risk of
      serious side effects on healthy skin in the course of topical photodynamic
      treatment. But the lack of dark toxicity and the time-dependent enrichment of
      both dyes in HaCaT cells are arguments for the application of these sensitizers
      in topical PDT of non-malign skin disorders. Further studies are necessary to
      discover appropriate lower doses and mechanisms of action of topical PDT with
      both compounds.

PMID- 17035717
TI  - In vitro percutaneous absorption and in vivo stratum corneum distribution of an
      organic and a mineral sunscreen.
AB  - Sunscreens, whose main function is to protect the skin against the harmful
      effects of solar irradiation, should remain at the skin surface or impregnate the
      first layers of the stratum corneum only and not penetrate into the underlying
      living tissue. The goal of this work was to assess the penetration of titanium
      dioxide (TiO(2)) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT),
      included in a broad-spectrum sunscreen formulation, into human skin in vivo,
      using the tape stripping method, and in vitro, using a compartmental approach. An
      additional objective was to propose an easy and minimally invasive approach to
      determining the percutaneous uptake of sunscreens following topical application.
      TiO(2) and MBBT were quantified using colorimetric assay and HPLC analysis,
      respectively. The transmission electron microscopy and particle-induced X-ray
      emission techniques were used to localize the TiO(2) in skin sections. More than
      90% of both sunscreens was recovered in the first 15 tape strippings. In addition
      we have shown that the remaining 10% did not penetrate the viable tissue, but was
      localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT
      was detected in the receptor medium, and no TiO(2) was detected in the follicle,
      viable epidermis or dermis. Thus, this in vivo and in vitro penetration study
      showed an absence of TiO(2) penetration into the viable skin layers through
      either transcorneal or transfollicular pathways and negligible transcutaneous
      absorption of MBBT. However, differences in distribution within the stratum
      corneum reinforced the need for a complementary approach, using minimally
      invasive in vivo methodology and in vitro compartmental analysis. This
      combination represents a well-adapted method for testing the safety of topically
      applied sunscreen formulations in real-life conditions.

PMID- 17035718
TI  - Improvement of epidermal barrier properties in cultured skin substitutes after
      grafting onto athymic mice.
AB  - Barrier function in cultured skin substitutes (CSS) prepared from human cell
      sources was measured by noninvasive (surface hydration, transepidermal water
      loss) and invasive methods (water permeation, niacinamide flux) before and after
      grafting onto athymic mice. In vitro measurements were made on days 7 and 14.
      Although three of the four measures of barrier function improved markedly from
      day 7 to 14, the values obtained were still far from those obtained with native
      human skin controls. Additional CSS were grafted onto athymic mice on day 14, and
      skin was harvested 2 and 6 weeks after grafting. Grafting brought about a
      substantial decrease in all measurements by 2 weeks and almost complete
      normalization of barrier function after 6 weeks. The most sensitive measure of
      this recovery was niacinamide permeability, which decreased from (280 +/- 40) x
      10(-4) cm/h in vitro to (17 +/- 30) x 10(-4) cm/h 2 weeks after grafting and (5
      +/- 2) x 10(-4) cm/h 6 weeks after grafting, versus control values of (2 +/- 2) x
      10(-4) cm/h in human cadaver skin and (0.6 +/- 0.4) x 10(-4) cm/h in human
      epidermal membrane prepared from freshly excised breast skin. These results
      demonstrate the reformation of epidermal barrier function after transplantation
      and provide insights for the development of a functional epidermal barrier in CSS
      in vitro.

PMID- 17035719
TI  - Real-timereflectance confocal microscopy, a noninvasive tool for in vivo
      quantitative evaluation of comedolysis in the rhino mouse model.
AB  - BACKGROUND: Near-infrared reflectance confocal microscopy (RCM) is a noninvasive
      tool that provides real-time images of thin virtual horizontal tissue sections.
      AIMS/METHODS: We have used a rhino mouse model in combination with topical
      application of all-trans-retinoic acid and all-trans-retinol to investigate the
      usefulness of RCM as a noninvasive imaging tool to evaluate comedolysis in vivo
      and over time. Optical images were correlated with routine histology. RESULTS:
      Our results demonstrate that RCM in vivo can visualize the process of
      transformation of utriculi (pseudocomedones) towards a normal-appearing
      follicular structure during retinoid treatment. The retinoic acid intervention
      group showed a dose-related response, while the vehicle-treated group did not
      show utricular changes. CONCLUSIONS: RCM represents a useful tool for in vivo
      morphological and quantitative evaluation of skin utriculi over time and could be
      used as an adjunct tool to histopathological techniques for comedolysis studies.

PMID- 17035720
TI  - In search for new antipsoriatic agents: NAD topical composition.
AB  - The aim of the study was to examine the effectiveness of the oxidized form of
      nicotinamide adenine dinucleotide (NAD(+)), adenosine precursor, in 37 patients
      suffering from psoriasis. As NAD(+) is known to be relatively unstable, the
      second goal was to establish the proper conditions for the satisfactory stability
      of topical NAD(+) composition. In each patient, two matching plaques were
      selected for the study. Topical treatment with 1 or 0.3% NAD(+) in Vaseline
      ointment administered twice daily was compared with overnight therapy with 0.1%
      anthralin applied for 12 h and placebo. The enzymatic method was applied to
      determine the stability of NAD(+) in Vaseline ointment. After a 4-week
      application, the reduction in erythema, infiltration and desquamation caused by 1
      or 0.3% topical NAD(+) composition was similar to the reduction caused by 0.1%
      anthralin. It was demonstrated that NAD(+) underwent a considerable decomposition
      at room temperature, while it was sufficiently stable at 5 degrees C; thus, for a
      longer use the agent should be stored at fridge temperature. NAD(+) therapy
      combines good efficacy, cosmetic acceptability and convenient twice-daily
      application.

PMID- 17035721
TI  - Anti-inflammatory and skin-hydrating properties of a dietary supplement and
      topical formulations containing oligomeric proanthocyanidins.
AB  - BACKGROUND: Anti-inflammatory and skin hydration properties of a dietary
      supplement and 2 topical formulations (Anthogenol) with oligomeric
      proanthocyanidins were investigated. METHODS: Forty-two subjects were randomized
      into 2 groups: one taking the dietary supplement (100 mg/day) and the other
      without supplement. After 4 weeks, erythema was induced using UV radiation
      followed by treatment with topical cream or lotion. Erythema was measured for up
      to 72 h after irradiation. Skin hydration after 1 and 2 weeks of application of
      the cream and lotion was also measured in separate test fields. RESULTS: Both
      topical formulations led to a significant suppression of erythema formation and
      the dietary supplement led to an additional slightly stronger suppression. Thus
      72 h after UV exposure and compared to the control fields of patients that had
      not taken a dietary supplement, erythema was slightly (13.2%) lower in the
      subjects that had taken a dietary supplement. The cream resulted in a maximal
      reduction of erythema of 45.9% (p = 0.0015), while the lotion resulted in a
      maximal reduction of 53.1% (p = 0.0002). Both topical formulations also increased
      skin hydration (by nearly 20%; p < 0.002 for all combinations of dietary
      supplementation and topical treatment) and the hydration was higher in the group
      taking the dietary supplement. CONCLUSION: The regular use of Anthogenol products
      may help to protect from free-radical-mediated skin inflammation and to increase
      skin hydration.

PMID- 17035722
TI  - Topical bioavailability of triamcinolone acetonide: effect of occlusion.
AB  - BACKGROUND/AIMS: Occlusion by covering the skin with an impermeable wrap enhances
      skin hydration, affects drug absorption and can induce the formation of a drug
      reservoir within the stratum corneum. This is desired in local therapy with
      topical corticosteroids. The aim of the study was to investigate the effect of
      occlusion before (experiment 1) and after (experiment 2) application on the
      penetration of triamcinolone acetonide (TACA) into the stratum corneum. METHODS:
      The experiments were conducted on the forearms of 10 healthy volunteers. In
      experiment 1, 100 microg/cm(2) TACA in acetone were applied on 3 sites per arm,
      one arm having been pre-occluded for 16 h. In experiment 2, the same dose was
      applied on 2 sites per arm, and one arm was occluded after application until skin
      sampling. Stratum corneum samples were removed by tape stripping at 0.5, 4 and 24
      h (experiment 1) and 4 and 24 h (experiment 2) after application. Corneocytes and
      TACA were quantified by ultraviolet-visible spectroscopy and HPLC, respectively.
      The total TACA amount penetrated into the stratum corneum was evaluated by
      multifactor ANOVA. RESULTS: TACA penetration into the stratum corneum with and
      without pre-occlusion (experiment 1) showed no significant difference and
      decreased with time. Occlusion after application (experiment 2) produced a marked
      TACA accumulation within the stratum corneum, which persisted for 24 h.
      CONCLUSION: Pre-occlusion showed no effect on the topical bioavailability of TACA
      in the stratum corneum. In contrast, post-occlusion enhanced the TACA penetration
      by a factor of 2, favouring the development of a drug reservoir.

PMID- 17035723
TI  - Influence of applied quantity of sunscreen products on the sun protection factor-
      a multicenter study organized by the DGK Task Force Sun Protection.
AB  - It is often debated that the protection against solar-induced erythema under real
      conditions is dependent upon the amount of sunscreen applied. It is believed that
      when too little is applied a lower sun protection than indicated on the label
      will result. The aim of this study was to quantify this effect. In this
      multicenter study, the influence of three different amounts (0.5, 1.0, 2.0
      mg/cm(2)) of three commercial sunscreen products in three reliable test centers
      was investigated according to the test protocol of The International Sun
      Protection Factor Test Method. The main result was a linear dependence of the SPF
      on the quantity applied. Taking into consideration the volunteer-specific
      variations, an exponential dependence of confidence interval of the in vivo SPF
      and amount applied was found. The highest amount applied (2.0 mg/cm(2)) was
      linked to the lowest confidence intervals. Thus, from the point of view of
      producing reliable and reproducible in vivo results under laboratory conditions,
      the recommendation of this multicenter study is an application quantity of 2.0
      mg/cm(2).

PMID- 17035725
TI  - Phytic acid: a phytochemical with complementary and alternative benefits.

PMID- 17035724
TI  - The roles of autophagy in cerebral ischemia.
AB  - Recent studies indicate the existence of autophagy in cerebral ischemia, but the
      functions of autophagy in this setting remain unclear. Here we discuss the role
      of autophagy in cerebral ischemia based on our own publication and the literature
      on this subject. We propose that oxidative and endoplasmic reticulum (ER)
      stresses n cerebral ischemia-hypoxia are potent stimuli of autophagy in neurons.
      We also reviewed evidence suggesting autophagosomes may have a shorter half-life
      in neurons and that a fraction of LC3 protein is degraded within autolysosomes,
      leading to a smaller detectable amount of LC3-II in the brain while there are
      clear indications of on-going autophagy. Finally, we suggest autophagy is an
      important modifier of cell death and survival, interacting with necrosis and
      apoptosis in determining the outcomes and final morphology of deceased neurons.

PMID- 17035726
TI  - Thymidylate synthase as a chemotherapeutic drug target: where are we after fifty
      years?

PMID- 17035727
TI  - The problem of platinum resistance.

PMID- 17035728
TI  - Delivering papillomavirus vaccines when and where they are most needed.

PMID- 17035729
TI  - Enhancing the efficacy of photodynamic therapy by a chinese herbal medicine for
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) ranks the sixth among the most common
      malignancies, with chronic HBV infection being the most common cause. HCC is more
      common in Africa, China and south-east Asia, but its incidence in the USA, Canada
      and Australia is rising. Current treatment modalities for HCC are not effective,
      and only a small percentage of patients are suitable for surgical resection and
      liver transplantation. Thus other treatment options and improvement of available
      modalities are badly in need. Photodynamic therapy (PDT) may have some
      therapeutic benefit for patients with HCC. The study by Tang et al. has
      implicated that coupled with Pheophorbide a (Pa), PDT may offer therapeutic
      benefit for patients with HCC. Inhibition of cell proliferation and induction of
      apoptosis by Pa may be mechanistically responsible for Pa-PDT. As Pa is an
      extract from a Chinese herbal medicine Scutellaria Barbata, which is widely
      available, less toxic and less expensive, such a combination may find a better
      clinical usage in the treatment of HCC patients. More studies are mandatory to
      fully elucidate the efficacy and mechanisms of Pa-mediated PDT.

PMID- 17035730
TI  - Safety and immunogenicity of a combination measles, mumps, rubella and varicella
      vaccine (ProQuad).
AB  - BACKGROUND: A combination measles, mumps, rubella, and varicella vaccine
      (ProQuad, Merck & Co., Inc, West Point, PA) was evaluated in five clinical
      trials. Use of ProQuad would result in fewer injections for children and would
      facilitate universal immunization against all four diseases. OBJECTIVE: To
      describe the combined results obtained from the studies conducted during the
      clinical development program for ProQuad. METHODS: A total of 5833 healthy
      children, 12-23 months of age, and 399 healthy children, 4-6 years of age,
      received 1 or 2 doses of ProQuad in five controlled clinical trials. M-M-R II and
      VARIVAX were used as the control for most studies. Safety was evaluated for six
      weeks postvaccination and immunogenicity was assessed six weeks after each dose
      by a sensitive assay (ELISA or gpELISA). RESULTS: A single dose of ProQuad in 12-
      to 23-month-old children was shown to be as immunogenic as a single dose of M-M-R
      II and VARIVAX and was generally well tolerated. ProQuad can be used
      concomitantly with other vaccines (hepatitis B and Hoemophilus influenzoe b). A
      higher rate of fever was reported after 1 dose of ProQuad compared to M-M-R II
      and VARIVAX, but fever episodes were transient without long-term sequelae. Both a
      2-dose regimen of ProQuad in 12- to 23-month-olds and use of ProQuad in place of
      M-M-R II at 4-6 years were shown to be immunogenic and well tolerated. The
      incidence of adverse experiences following a second dose of ProQuad was lower
      than that following the initial dose. CONCLUSIONS: A single dose of ProQuad is as
      immunogenic as M-M-R II and VARIVAX and is well tolerated in a 1- or 2-dose
      schedule. ProQuad should easily fit into the routine immunization schedule.

PMID- 17035731
TI  - Preclinical evaluation of a chimeric malaria vaccine candidate in Montanide ISA
      720: immunogenicity and safety in rhesus macaques.
AB  - Several malarial antigens are in development as potential vaccine candidates as
      part of a concerted effort to control the disease, which kills more than one
      million people per year. Although some antigens have demonstrated an impact
      against the malaria parasite, Plasmodium falciparum, many researchers hypothesize
      that a combination of antigens will be required to generate high levels of
      efficacy against clinical disease. PfCP2.9 is a chimeric protein that includes
      MSP119 and domain III of AMA1 [AMA1 (111)] of Plasmodium falciparum in a single
      recombinant molecule. The antigen, formulated in Seppic's ISA 720 adjuvant, is
      approaching Phase I clinical testing in humans. The purpose of this study was to
      assess the safety of this vaccine and to explore possible dosage levels for
      clinical evaluation. Groups of five monkeys each were immunized i.m. with 25
      microg, 50 microg, 100 microg and 200 microg of PfCP2.9/ISA 720 in 0.5 mL on days
      0 and 112. The mean anti-PfCP2.9 titres to the 50 microg dose group were higher
      than the other dose groups; however, there was no statistically significant
      difference between the anti-CP2.9 titres of any of the groups, suggesting that
      the immune response to PfCP2.9 was saturated at 25 microg. One animal in the 100
      microg dose group elicited a higher antibody and IFN-gamma response to PfCP2.9
      than the rest of the cohort; this animal developed a small sterile abscess
      following the second vaccination, which spontaneously resolved within one week.
      IN CONCLUSION: (a) 50 microg is highly immunogenic, appears safe, and is likely
      to be an appropriate dose for clinical evaluation; and (b) a conservative trial
      design is warranted to avoid any unexpected reactogenicity with the PfCP2.9/ISA
      720 formulation.

PMID- 17035732
TI  - Is autophagy the key mechanism by which the sphingolipid rheostat controls the
      cell fate decision?
AB  - Sphingolipids are major constituents of biological membrane and some of them
      behave as second messengers involved in the cell fate decision. Ceramide and
      sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide
      promotes cell death and S1P increases cell survival. We have shown that both
      sphingolipids are able to trigger autophagy with opposing outcomes on cell
      survival. Here we discuss and speculate on the diverging functions of the
      autophagic pathways induced by ceramide and S1P, respectively.

PMID- 17035733
TI  - Long term responses with cetuximab therapy in glioblastoma multiforme.

PMID- 17035734
TI  - Comparison of saftey and immunogenicity of purified chick embryo cell rabies
      vaccine (PCECV) and purified vero cell rabies vaccine (PVRV) using the Thai Red
      Cross intradermal regimen at a dose of 0.1 ML.
AB  - Intradermal (ID) vaccination with modern cell culture rabies vaccines is a means
      to significantly reduce the cost of post-exposure prophylaxis as compared to
      intramuscular vaccination. In this study we evaluated the efficacy,
      immunogenicity and tolerability of PCECV and PVRV administered ID in doses of 0.1
      mL per site according to the 2-site Thai Red Cross (TRC) regimen. Patients with
      WHO category III exposure to suspect or laboratory proven rabid animals were
      administered either PCECV (n = 58) or PVRV (n = 52) ID at a dose of 0.1 mL per
      site at two sites on days 0, 3 and 7 and at one site on days 30 and 90. Serum
      samples were withdrawn on days 0, 14, 30, 90 and 180 and rabies virus
      neutralizing antibody (RVNA) titers were determined by rapid fluorescent focus
      inhibition test (RFFIT). Patients who were exposed to laboratory confirmed rabid
      animals were followed up for one year after exposure. All 110 patients developed
      RVNA titers above 0.5 IU/mL by day 14. Adequate titers >0.5 IU/mL were maintained
      up to day 180. Both vaccines induced equivalent RVNA titers at all time points
      and were well tolerated. Five subjects who were bitten by laboratory confirmed
      rabid dogs were alive and healthy one year after exposure. As demonstrated, PCECV
      and PVRV are both immunogenic, efficacious and well tolerated when administered
      in the TRC post-exposure prophylaxis regimen in ID doses of 0.1 mL as recommended
      by WHO guidelines. The use of PCECV in this regimen may prove more economical in
      developing countries like India.

PMID- 17035735
TI  - Fever as a marker of reactogenicity of an acellular pertussis-containing
      hexavalent vaccine (HEXAVAC) in a large-scale, open, randomized safety study in
      healthy French infants.
AB  - OBJECTIVE: New multivalent vaccines simplify childhood immunisation schedules and
      can increase vaccination coverage. However, they must have a reactogenicity
      profile which is acceptable and comparable with that of previously available
      vaccines. The objective of this trial was to assess the incidence of fever of
      40.0 degrees C or higher following vaccination with HEXAVAC or concomitant
      PENTACOQ and HBVAXPRO. STUDY DESIGN: This was an open, randomized, pragmatic,
      post-licensure multicenter trial performed in France. Infants were randomly
      assigned to receive either a single injection of a hexavalent, aP-containing
      vaccine (HEXAVAC) or separate injections of a pentavalent, wP-containing vaccine
      (PENTACOQ) and Hepatitis B vaccine (HBVAXPRO) at 2, 3 and 4 months of age. Both
      groups received a HEXAVAC booster at 12-18 months of age. RESULTS AND DISCUSSION:
      7151 infants were enrolled in 389 centers. During the combined three-day periods
      following the primary series injections, the incidence of fever of 40.0 degrees C
      or higher with HEXAVAC was not greater than with [PENTACOQ and HBVAXPRO]. The
      incidence of fever at thresholds of 38.0 degrees C, 38.5 degrees C, 39.0 degrees
      C and 39.5 degrees C was significantly lower in the HEXAVAC group. The vaccine
      attributable risk for fever of 40.0 degrees C following the booster injection
      with HEXAVAC was statistically acceptable. CONCLUSION: The incidence of fever of
      40.0 degrees C or higher in this study was very low and similar in both groups
      (HEXAVAC or [PENTACOQ + HBVAXPRO] as a three-dose primary series). Fever > or
      =38.0 degrees C and < or =39.5 degrees C was significantly less frequent
      following administration of HEXAVAC. The incidence of fever of 40.0 degrees C or
      higher following a HEXAVAC booster dose was low in all infants studied.

PMID- 17035736
TI  - Activation of beta-catenin signaling pathways by classical G-protein-coupled
      receptors: mechanisms and consequences in cycling and non-cycling cells.
AB  - Wnt signaling pathways are some of the most intensely studies in all of biology.
      Recently, a number of classical heterotrimeric G protein coupled receptors
      (GPCRs) have been shown to activate the canonical Wnt pathway, culminating in the
      stabilization of beta-catenin and induction of transcription of genes regulated
      by the Tcf/Lef family of transactivators. However, mechanisms by which these
      GPCRs accomplish this differ in key ways, and in some circumstances, the
      phenotypes produced are novel. Herein, we will examine mechanisms by which
      classical GPCRs interact with the canonical Wnt pathway, culminating in its
      activation, and describe the consequences of this activation, focusing on the
      heart. In the heart, the contractile cells, or cardiomyocytes, are terminally
      differentiated and virtually exclusively grow by increasing cell size
      (hypertrophy) rather than cell number, and we will describe how GPCR-mediated
      activation of the canonical pathway can drive this process.

PMID- 17035738
TI  - The politicization of antimicrobial resistance.

PMID- 17035737
TI  - A fluorescent peptide substrate for measuring the ADP-ribosylation activity of
      the cholera toxin A-subunit.
AB  - Vibrio cholerae serogroups O1 and O139 Bengal produce cholera toxin (CT) a
      typical AB5 bacterial toxin comprising an ADP-ribosylation enzyme A-subunit (CTA)
      and a carbohydrate binding B-subunit (CTB). DUKORALR the inactivated oral cholera
      vaccine has recently been licensed for use in the European Union. This vaccine
      contains killed whole cells of V cholerae and 1 mg of purified recombinant CTB
      (rCTB). DUKORALR has a good safety profile and there has been no indication that
      active CT is present. Nevertheless, an assay that confirms the absence of active
      CTA in the vaccine is advantageous to ensure vaccine safety. Conventional assays
      such as the Y-cell assay cannot detect biologically active amounts of CT in
      DUKORALR because of the large amount of rCTB present. We have developed an assay
      based on a fluorescently labelled 11-mer peptide substrate that detects CTA
      activity despite the presence of excess rCTB.

PMID- 17035739
TI  - Glycopeptide resistance in staphylococci.
AB  - Glycopeptide antibiotics have become the last bastion for the treatment of
      multidrug-resistant Gram-positive hospital pathogens, the two main ones being
      methicillin-resistant S. aureus and enterococci. However, in addition to the
      emergence of vancomycin resistance in enterococci, certain staphylococcal strains
      with low-level resistance to glycopeptides have increasingly been isolated from
      clinical specimens. This review focuses on mechanisms of resistance,
      epidemiology, control measures and therapeutic options for these staphylococci.

PMID- 17035740
TI  - Treatment of otitis media.
AB  - Otitis media is a very common reason for the prescription of antibiotics in
      children. Antimicrobial therapy is mostly empirical, based on the knowledge of
      the frequency and susceptibility patterns of causative pathogens and of the
      penetration and other pharmacokinetic properties of several oral antibiotics.
      Pharmacoeconomic considerations must also be taken into account.

PMID- 17035741
TI  - New antimicrobial agents for Gram-positive infections.
AB  - Increasing antimicrobial resistance in Gram-positive bacteria has presented a
      formidable treatment problem. The enterococci, although traditionally non
      virulent pathogens, have been shown, when associated with vancomycin resistance,
      to have an attributable mortality of approximately 40%. The frightening specter
      of widespread vancomycin resistance in the more virulent Staphylococcus aureus
      would have a significantly greater impact. Since the late 1980s, advances have
      been made in the development of pharmacological weapons against multiply
      resistant Gram-positive bacterial infections. At least seven new antimicrobial
      classes that have activity against resistant Gram-positive organisms are in
      various stages of development. Most are semisynthetic derivatives of known
      antibiotics; however, importantly, a unique class of antimicrobial agent has also
      emerged.

PMID- 17035742
TI  - Pharmacokinetic and pharmacodynamic modelling of antibiotic therapy.
AB  - Despite the advances in pharmacokinetic and pharmacodynamic modelling, there is
      still much more to gain from this concept. The use of pharmacokinetic and
      pharmacodynamic modelling in vitro, in animal and in human models has confirmed
      that an index, such as peak concentration divided by the minimum inhibitory
      concentration (Cmax/MIC), the area under the curve divided by the minimum
      inhibitory concentration (AUC/MIC) and time above the minimum inhibitory
      concentration (T>MIC), may be used as an aid to understanding better the
      variability between patients who receive similar antibiotic dosage regimens but
      have dissimilar outcomes. Efforts to find the optimal pharmacokinetic or
      pharmacodynamic index predictive of response is crucial to identify targets that
      will ensure efficacy and for the prediction of failure.

PMID- 17035743
TI  - Immunological effects of macrolides.
AB  - Various reviews have highlighted the potential immuno-modulating properties of
      macrolides. Recent data in this field raise the possibility of new therapeutic
      prospects in cancer and inflammatory diseases (cystic fibrosis, asthma,
      atherosclerosis, etc.). Advances have also been made in our understanding of the
      interactions between macrolides and host immune effectors, particularly
      phagocytes. The third millennium should see exciting new uses of macrolides.

PMID- 17035745
TI  - Chemotherapy of malaria.
AB  - Clinical trials continue to provide evidence for the efficacy of semi-synthetic
      artemisinin derivatives and the novel fixed dose combination therapies Malarone,
      co-artemether and chlorproguanil-dapsone. Single agents under development include
      the 8-aminoquinoline etaquine, pyronaridine and azithromycin. Preclinical
      interest in synthetic endoperoxides and quinoline analogues remains high and a
      significant is also being made in natural product chemistry. Dihydrofolate
      reductase remains a molecular drug target of interest, whereas phospholipid
      metabolism represents a new approach. Genomic information is likely to produce
      many new drug targets for exploration in the coming decade.

PMID- 17035746
TI  - Chemotherapy of leishmaniasis: recent advances in the treatment of visceral
      disease.
AB  - New lipid formulations of amphotericin B--AmBisome, Amphotec, and Abelcet--have
      dramatically decreased the toxicity associated with amphotericin B and have made
      this group of agents the treatment of choice for visceral leishmaniasis. An agent
      of a completely different chemical class, the aminoglycoside aminosidine, was 97%
      curative in India. This agent too may be used for visceral leishmaniasis.

PMID- 17035747
TI  - Changing patterns of disease and treatment of opportunistic parasitic infections
      in patients with AIDS.
AB  - In the past 18 months, the significant effect of highly active antiretroviral
      therapy and immune reconstitution on the incidence of opportunistic protozoan
      infections, mainly cryptosporidiosis and microsporidiosis, has been demonstrated
      in HIV-infected patients. The major therapeutic advances of the past 18 months
      concern microsporidiosis, for which the efficacies of fumagillin and albendazole
      have been assessed against Enterocytozoon bieneusi and Encephalitozoon
      infections, respectively. The efficacy of macrolides is still uncertain for the
      treatment of cryptosporidiosis; however, promising results were obtained with
      nitazoxanide. The incidence of toxoplasmosis has markedly decreased as a result
      of the efficacy of specific prophylaxis, and visceral leishmaniasis is still
      considered as an emerging opportunistic disease during AIDS.

PMID- 17035749
TI  - New therapies for the treatment of chronic hepatitis B infection.
AB  - Persistent hepatitis B virus infection can lead to the development of chronic
      liver disease, cirrhosis and primary hepatocellular carcinoma. The only therapy
      of confirmed benefit in chronic hepatitis B is interferon alpha, which can lead
      to long-term benefit in only a third of highly selected patients. A number of new
      therapeutic approaches are being actively developed for treating chronic
      hepatitis B, including the use of nucleoside analogues, cytokines, antisense
      oligonucleotides, ribozymes, dominant negative mutants and DNA-based vaccines.
      Recent clinical trials with the nucleoside analogues have identified several
      important challenges for future drug development, in which the gene therapy-based
      approach may prove useful either alone or most probably in various combinations.
      Future clinical trials should aim to address these challenges using the new
      therapies so that the goal of substantial and sustained inhibition of viral
      replication with the accompanying improvement in the underlying liver disease can
      be achieved.

PMID- 17035750
TI  - In-vitro and in-vivo efficacy of influenza neuraminidase inhibitors.
AB  - Influenza continues to be a major health concern and there is always the threat
      of a pandemic due to the emergence of a viral strain new to the human population,
      as exemplified by the avian influenza A/H5N1 virus which was responsible for six
      deaths in Hong Kong last year. Data reported in the past year, based on in-vitro,
      in-vivo (animal) and clinical studies, suggest that a new class of antiviral
      compounds targeting the viral neuraminidase is likely to be useful for the
      treatment and prevention of influenza virus infections in humans.

PMID- 17035751
TI  - Specific therapies for human papilloma virus infections.
AB  - Human papillomavirus induces the hyperproliferation of epithelial cells, leading
      to a broad spectrum of human diseases, ranging from benign warts to malignant
      neoplasms, depending on the location of the lesion, the immune status of the
      patient and the type of human papillomavirus. Current therapies for human
      papillomavirus-associated diseases are based on the excision or ablation of
      dysplastic or malignant tissue, and are associated with a high frequency of
      recurrent disease, discomfort and costs. A better understanding of the viral
      replicative cycle and of the interaction between the virus and the host cell,
      particularly the cell cycle regulation, has opened new perspectives. Recently,
      new treatment modalities for human papillomavirus-induced lesions have been
      identified, including the use of antiviral/immunomodulatory therapies, such as
      cidofovir, antisense oligonucleotides, imiquimod and human papillomavirus
      vaccines.

PMID- 17035752
TI  - Treatment guidelines and clinical realities.

PMID- 17035753
TI  - Latent reservoirs for HIV-1.
AB  - Combination therapy for HIV-1 infection can reduce viremia to undetectable
      levels, suggesting that prolonged treatment might eradicate the infection.
      However, one potential mechanism for viral persistence involves the establishment
      of a state of latent infection. Recent studies have directly confirmed that HIV-1
      establishes a state of latent infection in resting memory CD4(+) T cells in vivo.
      This reservoir is likely to frustrate current efforts to eradicate the infection
      with combination therapy.

PMID- 17035754
TI  - Metabolic abnormalities and body fat redistribution in HIV-1 infected patients:
      the lipodystrophy syndrome.
AB  - A unique and unexpected syndrome consisting of metabolic abnormalities
      (hyperlipidaemia and insulin resistance) and body fat redistribution (central
      adiposity and peripheral fat wasting) has been reported with increasing frequency
      in HIV-1 infected patients, most of whom are receiving highly active
      antiretroviral therapies including HIV-1 protease inhibitors. This article
      reviews the clinical and laboratory characteristics, the pathogenesis, and the
      management of this syndrome.

PMID- 17035755
TI  - Mother to infant transmission of HIV.
AB  - Mother-to-infant transmission is the route by which the vast majority of children
      acquire HIV. Several refinements in our understanding in how to reduce the risk
      of transmission have been made in the past year. The risks from prolonged breast
      feeding, and the protective effects of caesarean section have been clarified.
      Shorter interventions using antiretroviral drugs are useful in resource
      constrained settings. In developed countries, combination antiretroviral
      therapies to reduce maternal viral loads to below limits of detection are being
      explored, but there is concern about toxicity particularly of indinavir in
      pregnancy. Combining interventions can reduce transmission rates to less than 2%.

PMID- 17035756
TI  - HIV drug resistance tests are here to stay.
AB  - The clinical indications for HIV drug resistance testing are discussed. The major
      limitations of using resistance testing in the clinical setting are the lack of
      evidence for a clinical benefit, the costs and the amount of knowledge required
      for a good interpretation of the results. In those situations in which these
      limitations can be overcome or are considered less important, resistance testing
      may be used today. For widespread clinical use, however, trials creating large
      databases and the design of expert systems translating the results for the use in
      individual patients will be required.

PMID- 17035758
TI  - Importance of drug resistance in gonococci: from mechanisms to monitoring.
AB  - Neisseria gonorrhoeae isolates continue to develop an impressive arsenal of
      resistance mechanisms to antimicrobial agents, including resistance to some of
      the antibiotics presently recommended for the treatment of gonococcal infections.

PMID- 17035759
TI  - Which test is best for chlamydia?
AB  - Nucleic acid amplification tests are now the tests of choice for diagnosing
      Chlamydia trachomatis infection. For the first time there are diagnostic tests
      for Chlamydia trachomatis that are more sensitive than tissue culture. Another
      major advantage is that they can be used with first-catch urine specimens and
      vaginal swabs. It is thus possible to test for genital chlamydial infection
      without using invasive specimen collection methods.

PMID- 17035760
TI  - In pursuit of a human chlamydial vaccine.
AB  - The best way to control chlamydial diseases is with an effective vaccine.
      Although previous studies suggest that a vaccine is an achievable goal, progress
      has been limited even though many vaccination strategies have been tested. A
      clearer understanding of the immunobiological basis of chlamydial protection and
      pathology will be critical for future research in chlamydial vaccination.

PMID- 17035761
TI  - Bacterial vaginosis: sequelae and management.
AB  - The prevalence and complications of bacterial vaginosis are population dependent.
      In pregnancy, bacterial vaginosis is associated with late miscarriages and
      infection driven pre-term delivery. Regardless of the aetiology of pre-term
      delivery, surviving infants are at increased risk of subsequent
      neurodevelopmental handicap. Intervention studies in bacterial vaginosis positive
      pregnant women at high risk of pre-term delivery demonstrate the benefits of
      antibiotic treatment. Current evidence suggests that bacterial vaginosis may
      increase the efficiency of heterosexual HIV transmission. Metronidazole remains
      the mainstay of treatment of bacterial vaginosis. No treatment prevents relapse,
      which occurs in 20-30% of cases within 1 month. New approaches that are based on
      a better understanding of the pathophysiology of bacterial vaginosis are required
      to improve the clinical management of recurrent bacterial vaginosis.

PMID- 17035762
TI  - Novel strategies for treating candidiasis.
AB  - In this review the recent achievements in the field of chemotherapy and
      immunotherapy of candidiasis are outlined. The current limitations of
      chemotherapeutic approaches and the lack of well defined preventive tools and
      strategies make it imperative to exploit the potential of novel immunotherapeutic
      venues. In this prospect the rather extensive work performed on cytokine patterns
      in experimental models and the upsurge of antibodies as one mechanism of anti
      Candida protection raises great promise for the clinical use of immunotherapy
      possibly in conjunction with chemotherapy to improve the fight against this
      increasingly prevalent human opportunistic infection.

PMID- 17035763
TI  - Interactions between human papillomavirus and other sexually transmitted agents
      in the etiology of cervical cancer.
AB  - The interplay between human papillomavirus, notably type 16, and HIV in cervical
      carcinogenesis leads to persistent infection and cervical neoplasia by
      destruction of the afferent arm (Langerhans cells) of the host immune system. The
      joint effect takes place at the early stages of squamous intraepithelial lesions
      and has severe consequences if left untreated. The recent increase of cervical
      cancer mortality in young women in developed countries may well be a result of
      the HIV epidemic. Infection with Chlamydia trachomatis is associated with
      cervical squamous cell carcinoma but not with cervical adenocarcinoma, and the
      association remains after adjusting for human papillomavirus 16. Joint effects of
      C. trachomatis and the human papillomaviruses have not been studied at the
      population level but indirect evidence from epidemiological studies suggests that
      the interaction might be different (synergistic versus antagonistic) at different
      stages (cervical intraepithelial neoplasia versus invasive cervical cancer) of
      cervical carcino-genesis. Concomitant exposure to human papillomaviruses 6 or 11
      and human papillomavirus type 16 has not been shown to result in excess risk of
      cervical squamous cell carcinoma. This antagonistic joint effect was also
      discovered between human papillomavirus types 18 and 16, as well as 33 and 16.
      Herpes simplex virus type 2 antibodies are associated with a modest risk of
      cervical cancer, which is not surprising since the presence of herpes simplex
      virus antibodies reflects risk-taking sexual behaviour. However, no excess risk
      remains after adjustment for human papillomavirus type 16, and no interaction
      between these two viruses has been found in epidemiological studies. Evidence of
      interaction between human papillomavirus type 16 and the other members of the
      herpesvirus family is still at an experimental level and difficult to judge.
      Little progress has been made in the most promising experimental association
      between the oncogenic human papillomaviruses and adeno-associated viruses. In
      addition to the well established interaction between human papillomaviruses and
      HIV, intriguing interactions are emerging between the human papillomaviruses and
      C. trachomatis, as well as between the different human papillomavirus types.

PMID- 17035764
TI  - Current world literature.

PMID- 17035765
TI  - Acute bronchitis: an indication for antibiotic avoidance.

PMID- 17035766
TI  - Laboratory diagnosis of respiratory infections.
AB  - The laboratory diagnosis of infections of the respiratory tract is not an exact
      science, with many clinicians electing to empirically select antimicrobial
      therapy without the benefit of laboratory testing. With trained laboratory
      personnel and the proper selection of tests, accurate laboratory diagnosis is
      available. Progress is occurring most rapidly with molecular methods, such as
      polymerase chain reaction (PCR) testing. As molecular approaches are technically
      simplified and become less expensive, advances in the laboratory diagnosis of
      most respiratory tract infections caused by fastidious pathogens will occur. The
      diagnosis of non-fastidious bacteria, that require in-vitro antimicrobial
      testing, will continue to require conventional culture methods. New bronchoscopic
      methods, quantitative evaluation of cultures, and recognition of intracellular
      bacteria in stained smears do improve the usefulness of conventional culture and
      stain in the diagnosis of pneumonia.

PMID- 17035767
TI  - The other causes of 'atypical' pneumonia.
AB  - Mycoplasma, Chlamydia and Legionella are the usual organisms considered to be the
      etiologic agents of 'atypical' pneumonia. Other microorganisms such as bacteria,
      viruses, parasites, fungi and mycobacteria can also present with atypical
      pneumonia manifestations. Outbreaks and isolated cases of respiratory viruses
      with atypical pneumonia presentations have been reported among immunocompetent
      and immunosuppressed patients. Severe infections due to these respiratory viruses
      alone or as a concomitant bacterial or viral infection have been observed.
      Additionally, in endemic areas, certain zoonotic infections may present as
      atypical pneumonia.

PMID- 17035768
TI  - Update of Legionella infections.
AB  - Legionella spp. are significant causes of both community-acquired pneumonia and
      nosocomial pneumonia. More than 40 species of Legionella have now been
      identified. The spectrum of disease ranges from asymptomatic infection to serious
      disease, with two specific syndromes identified: Legionnaire's disease and
      Pontiac fever. Hospital-acquired infection arises from the presence of Legionella
      in the hospital water supply. The optimal approach for the detection and
      prevention of nosocomial infection is debatable-whether or not periodic sampling
      of hospital water systems should be carried out in the absence of clinical cases
      is controversial. Newer macrolides or newer fluoroquinolone agents are the
      preferred therapy for serious diseases caused by Legionella.

PMID- 17035769
TI  - Management decisions regarding community-acquired pneumonia.
AB  - The successful management of community-acquired pneumonia requires many
      management decisions, including a decision as to the site of care, the type and
      duration of antibiotic therapy, and a discharge decision for patients who require
      hospitalization. A number of recent studies have defined and tested criteria for
      some of the management decisions indicated above.

PMID- 17035770
TI  - Advances in antimicrobial therapy of community-acquired pneumonia.
AB  - Community-acquired pneumonia has a significant impact upon healthcare in North
      America and worldwide. In the U.S. it is responsible for three to four million
      cases yearly and 78,000 deaths. It is not a homogeneous entity and it may be
      caused by a number of pathogens including Streptococcus pneumoniae, the atypicals
      (Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species) Haemophilus
      influenzae and Gram-negative rods. While it is clear that directed therapy is the
      ideal, empiric therapy is likely to remain the norm for some time to come. This
      is because of limitations in current diagnostic techniques, the possibility of
      infection with co-pathogens and the broad spectrum of antimicrobial activity
      required to treat the various pathogens which may be responsible for infection in
      any given patient. Of great concern is the increase in the incidence of resistant
      pathogens seen in community-acquired pneumonia. Of particular significance are
      the isolates of S. pneumoniae which display resistance to penicillin and
      macrolides although the exact clinical relevance has yet to be determined. New
      guidelines for the treatment of community-acquired pneumonia have been developed
      by the Infectious Disease Society of America which include the new
      fluoroquinolones. These agents offer the potential for monotherapy of community
      acquired pneumonia in cases which previously required combination regimens such
      as a macrolide and a beta-lactam. There is great concern however, that these
      agents not be used inappropriately thereby hastening the emergence of resistance
      to the fluoroquinolone class of antimicrobials.

PMID- 17035772
TI  - Current world literature.

PMID- 17035771
TI  - Vaccines to prevent respiratory infection: opportunities on the near and far
      horizon.
AB  - Illnesses caused by respiratory pathogens result in great loss of life, suffering
      and commitment of resources for treatment. That the suffering and loss of life
      can be prevented through immunization has already been clearly shown with
      existing vaccines, such as those for Haemophilus influenzae type b, Streptococcus
      pneumoniae, and influenza. The emergence of drug-resistant pathogens is making
      reliance on therapy more expensive and perhaps less successful, accentuating the
      need to focus on prevention. Although several effective vaccines to prevent
      respiratory infections currently exist, they are underutilized globally.
      Improvements in immunogenicity, efficacy, and ease of administration, and
      lowering the costs of some of the existing vaccines would augment the potential
      for prevention worldwide. The greatest opportunities for the prevention of
      respiratory infections will rest with vaccines that will become available in the
      future.

PMID- 17035773
TI  - Microbial antigens, heat shock proteins and skin disease.

PMID- 17035774
TI  - Heat shock proteins and skin diseases.
AB  - Heat shock proteins are chaperones to construct protein molecules and are widely
      distributed in prokaryotic and eukaryotic cells. They are also induced by
      environmental stress to protect cells. Human heat shock proteins cross-react with
      bacterial heat shock proteins to modulate immune responses to induce
      autoimmunity. They are involved in the differentiation and growth of neoplastic
      cells as well as normal cells. They are also involved in various inflammatory
      skin diseases and in fibrotic process. Heat shock proteins play important roles
      in the pathogenesis of many skin diseases.

PMID- 17035775
TI  - Biology and epidemiology of scabies.
AB  - Only recently have attempts been made to develop techniques for the early
      identification of scabies infections and to identify the genome of the mites.
      Most work with scabies employs rudimentary technology and requires skill for
      accurate diagnosis. Many countries still have no widely available dermatology
      service to deal with this infection and its sequelae.

PMID- 17035776
TI  - Mycobacterium marinum infections.
AB  - Mycobacterium marinum is a saprophytic mycobacteria capable of causing soft
      tissue infection in humans, usually acquired by inoculation. As with other
      mycobacterial infections, diagnosis may be difficult and recent developments in
      molecular biology are also being applied to atypical mycobacteria such as
      Mycobacterium marinum.

PMID- 17035777
TI  - Molluscum contagiosum: new perspectives on an old virus.
AB  - Renewed interest in molluscum contagiosum virus has been stimulated by the
      availability of the entire genomic sequence and the identification of more than
      160 putative genes, some of whose functions are now under analysis. Important
      findings have been generated by the recognition that certain viral proteins have
      anti-chemotactic and anti-apoptotic properties. Other advances include the
      characterization of two recombinant immunoreactive proteins, and the publication
      of the first seroepidemiological survey of the general population. Recent
      clinical studies indicate that some of the newer antiviral agents and physical
      treatment modalities offer significant benefits for the treatment of recalcitrant
      infections in the immunosuppressed.

PMID- 17035779
TI  - Immunomodulation for the treatment and prevention of bacterial infections: a
      challenge for the next millennium.

PMID- 17035778
TI  - The immunology of Propionibacterium acnes and acne.
AB  - The majority of recent publications on the immunology of Propionibacterium acnes
      relate to the potential use of the bacterium as an adjuvant or its use in rodent
      models of human inflammatory disease. These studies have increased the
      understanding of the potential effects of Propionibacterium acnes on cells of the
      mononuclear phagocyte system. Research into the immunology of acne and the role
      that Propionibacterium acnes plays in inflammatory acne has been limited, with
      efforts being focussed on the problems of Propionibacterium acnes resistance to
      antibiotics. Recent studies have indicated that inflammatory acne is a T cell
      mediated disease, but whether Propionibacterium acnes is the initial stimulus for
      either the specific or non-specific recruitment of T cells in acne lesions is
      still a matter for conjecture.

PMID- 17035780
TI  - Infective endocarditis: new concepts in pathogenesis.
AB  - Gram-positive cocci account for the large majority of cases of infective
      endocarditis. Pathogenesis investigations of endocarditis have therefore focused
      on purported virulence factors in staphylococci, viridans group streptococci and
      enterococci. In addition to novel molecular techniques that have been adapted for
      use in the examination of gram-positive cocci, animal models of experimental
      endocarditis have been employed to support or discount the role of specific
      bacterial components in production of infective endocarditis. This review details
      recent work that addresses endocarditis pathogenesis and highlights pertinent
      findings from these investigations.

PMID- 17035781
TI  - Otitis media today: a challenge for physicians and the community.
AB  - Acute otitis media is one of the most common causes of medical consultation
      worldwide, and has a high economic impact. In this review, a clear definition
      between acute otitis media and otitis media with effusion is presented. The
      microbiology and characterization of the main bacterial isolates in acute otitis
      media and the susceptibility patterns are reviewed, and the latest concepts in
      antimicrobial treatment are discussed. The need for courses that improve the
      capability of primary care physicians to diagnose acute otitis media using
      pneumatic otoscopy, and for parental education is also discussed.

PMID- 17035782
TI  - Superantigens and autoimmune disease: are they involved?
AB  - In over 10 years since the definition of superantigens, much has been learned
      about host cell-superantigen interactions. The initial simple set of rules used
      to define these interactions has given way to a more complex system, in which the
      activation of multiple cell types can occur as a consequence of superantigen-cell
      interactions or as a result of bystander effects based on the induction of a
      specific cytokine milieu. As a consequence, our ideas concerning the ways in
      which superantigens might be involved in disease are also expanding rapidly. This
      review highlights some of the many different pathways of superantigen-associated
      pathogenesis currently under investigation.

PMID- 17035783
TI  - Host responses to secreted Shigella virulence factors.
AB  - Shigella and related enteropathogens deliver effector molecules into the
      cytoplasm of epithelial cells and macrophages via a type III secretion system.
      Epithelial cells respond to contact with Shigella by rearranging the
      cytoskeleton, which leads to uptake of the bacterium. Apart from several
      cytoskeletal proteins, this process involves the recruitment and activation of
      kinases, and the small GTPase rho. Macrophages infected with Shigella undergo
      apoptosis and release mature IL-1beta, a pro-inflammatory cytokine. This
      apoptotic pathway requires caspase-1 (IL-1beta-converting enzyme). Pro
      inflammatory macrophage apoptosis triggers acute shigellosis and might be
      relevant in other infectious diseases.

PMID- 17035784
TI  - Chlamydia trachomatis: the role of cellular and humoral immune mechanisms in the
      development of blindness.
AB  - Ocular infection with Chlamydia trachomatis leading to trachoma is the commonest
      cause of treatable blindness worldwide. Although effectively controlled by
      improved sanitation, a chlamydial vaccine may prove a more cost-effective method
      of protection against this disease in the medium term. The development of
      vaccines against Chlamydia trachomatis has been hampered by a lack of
      understanding of the immune responses leading to protection or pathology,
      particularly in humans. Although a strong cell-mediated immune response (T helper
      lymphocyte type 1) is almost certainly necessary to resolve intracellular
      chlamydial infection, a humoral (T helper lymphocyte type 2) response may protect
      against colonization and limit immunopathological events. Recent studies
      addressing this potential conflict are reviewed.

PMID- 17035785
TI  - Reactivation of herpes simplex virus: the role of cytokines and intracellular
      factors.
AB  - Considerable progress has been achieved in relating environmental stimuli and
      viral genetics to herpes simplex virus reactivation. The cytokines IL-1, IL-6,
      nerve growth factor NGF, and interferons have been implicated in herpes simplex
      virus reactivation. These molecules may act as signals which convey important
      information about the environment to the latent viral genome. Herpes simplex
      virus latency associated transcript expression is important for viral
      reactivation. The function of these unique viral RNA's is not completely
      understood, but they appear to be necessary for the efficient establishment of a
      latent infection in the ganglion. A better understanding of the mechanisms
      underlying the herpes simplex virus reactivation can be expected to lead to novel
      effective treatments for herpes simplex diseases.

PMID- 17035786
TI  - Association between the biological characteristics of HIV-1, vertical
      transmission of infection and clinical progression of pediatric disease.
AB  - The design of effective prophylactic measures to prevent the vertical
      transmission of HIV-1 and of therapies to alter the natural progression of
      pediatric HIV disease requires a thorough understanding of basic pathogenetic
      principles. Maternal viral load, the biological behavior of HIV, such as
      replicative capacity in different types of cells, monocyte/macrophage tropism,
      and the capacity of the infant's cells to support infection have all been
      assessed for their contribution to the risk of mother-to-child transmission.
      Similarly, the effects of viral load and phenotype (e.g. replicative capacity,
      cell tropism, syncytium-inducing capacity and the use of chemokine co-receptors)
      have all been investigated as parameters associated with variations in the
      expression of clinical disease in children. Some of the extant data are
      conflicting, but general principles regarding pathogenesis are beginning to
      emerge.

PMID- 17035787
TI  - Hepatitis C in children.
AB  - Mother-to-child, or vertical transmission, of hepatitis C virus is now the
      dominant mode of acquisition of infection for children. The rate of transmission
      is low in women who are not also HIV-positive. Whether the mode of delivery is
      associated with transmission remains questionable; breast-feeding does not appear
      to be a source of infection. The detection of hepatitis C virus RNA using the
      polymerase chain reaction is a sensitive method for the early diagnosis of
      infection in perinatally exposed infants, but false positive results can occur.
      The natural history of hepatitis C virus infection in children is not well
      defined, but chronic infection is common in most cases. The disease progression
      is slower than in adults. Therapeutic trials (not placebo controlled) in a small
      number of children suggested a sustained response to interferon treatment in only
      a minority of cases. The option of combination therapy with ribavirin looks
      promising and needs evaluation.

PMID- 17035788
TI  - The epidemiology and pathogenesis of infections caused by the high numbered human
      herpesviruses in children: HHV-6, HHV-7 and HHV-8.
AB  - Human herpesvirus 6 may be transmitted from saliva to infants, but other routes
      of transmission, such as organ and bone marrow transplantation, have also been
      reported. Intrauterine infection has also been suggested. Although the clinical
      symptoms during the primary infection in children are mild, human herpesvirus 6
      may have neurotropic properties and be involved in the pathogenesis of febrile
      seizures in infants. The clinical symptoms caused by human herpesvirus 7 are not
      yet clear, but reports have described neurological symptoms. Human herpesvirus 8
      has been identified from Kaposi's sarcoma tissue using molecular procedures.
      Serological study shows that human herpesvirus 8 is not so common in society and
      the mode of transmission is still unclear. Several routes of infection have,
      however, been considered, including sexual transmission.

PMID- 17035789
TI  - Rational treatment of pulmonary infections in patients with cystic fibrosis.
AB  - The life expectancy of patients with cystic fibrosis has increased markedly
      during the past two decades due in large part to improved clinical care,
      including the use of more effective antimicrobial agents for Pseudomonas.
      However, the chronic lung disease of CF remains the principal cause of mortality.
      A growing understanding of the complex interactions between infection and
      inflammation has led to new approaches for treatment, including chronic use of
      aerosolized antibiotics, particularly tobramycin, in patients known to be
      colonized/infected with P. aeruginosa and anti-inflammatory treatments to slow
      the progression of lung disease.

PMID- 17035790
TI  - Natural history and long-term consequences of Lyme disease in children.
AB  - Lyme disease is the most common vector-borne infection affecting children living
      in temperate parts of the western hemisphere. The widespread anxiety about the
      long-term consequences of the illness, however, finds no support in the
      literature. Although the number of long-term follow-up studies is limited, the
      prognosis in children treated for Lyme disease seems to be extremely favourable.

PMID- 17035791
TI  - Current world literature.

PMID- 17035792
TI  - Antibiotic resistance-systems thinking, chaos and complexity theory.

PMID- 17035793
TI  - Surveillance of antibiotic resistance.
AB  - Resistance among bacteria is on the rise, both in the hospital and in the
      community. Surveillance is needed for guided empiric treatment and to detect new
      resistance mechanisms at an early stage. Surveillance shows a wide variation in
      resistance among hospitals and countries. Especially methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant enterococci are uncommon in north
      western European countries but frequently observed otherwise elsewhere. Among
      Gram-negative bacteria regional differences are less obvious. Many hospitals all
      over the world suffer from recurrent outbreaks by Enterobacteriaceae that produce
      extended spectrum beta-lactamases, Acinetobacter, etc. Because of the evolving
      pattern of resistance, surveillance should be done at regular intervals in all
      hospitals and in the community.

PMID- 17035794
TI  - Lessons from recent nosocomial epidemics.
AB  - This review describes important examples of recent nosocomial infection
      epidemics. Current trends suggest that emerging problems in nosocomial infections
      include increased nosocomial epidemics in out-of-hospital settings, contamination
      of medical devices and products, and antimicrobial resistance. Increased
      attention should be focused on outbreak investigations in these areas.

PMID- 17035795
TI  - Nosocomial pneumonia.
AB  - Nosocomial pneumonia remains an important infection that warrants continuing
      investigation. The past year has seen a number of reports further describing risk
      factors, controversial issues around diagnosis, and potential preventive
      strategies. For specific infecting organisms such as Legionnaire's disease and
      tuberculosis, further reports of issues related to water supply in the former and
      staff preventive programs in the latter have also been reported. Substantive
      advances in prevention or management have not, however, been identified.

PMID- 17035796
TI  - Nosocomial diarrhoea.
AB  - Toroviruses have been reported as a new cause of nosocomial viral diarrhoea, and
      the role of astroviruses has been further elucidated. Polymerase chain reaction
      methods promise to improve the diagnosis and understanding of the aetiology and
      control of hospital-acquired viral gastroenteritis. A clearer picture of the
      impact and extent of Clostridium difficile diarrhoea has emerged, and several
      control measures have been described. An epidemic Clostridium difficile strain
      and toxin A-deficient strains have been reported. There is growing evidence that
      enterotoxin-producing Clostridium perfringens can also cause antibiotic
      associated diarrhoea.

PMID- 17035797
TI  - Orthopaedic implant infections.
AB  - Recent advances have defined risk factors for orthopaedic implant infections that
      suggest modifications in the clinical care of certain patients. For diagnosis,
      new work shows the importance of obtaining multiple specimens for culture, and
      the enlarging spectrum of causative organisms. The potential for the polymerase
      chain reaction is demonstrated. In treatment, the value of rifampicin is shown in
      controlled and open trials.

PMID- 17035798
TI  - Pathogen 'shift' in febrile neutropenia.

PMID- 17035799
TI  - Infection in the neutropenic and stem cell transplant patient.
AB  - The spectrum of infectious complications in neutropenic patients after stem cell
      or bone marrow transplant is not very different from that seen in other
      neutropenic patients, with the possible exception of fungal infections. The
      prevention and therapy of these infections remain a major challenge. The
      management of neutropenic patients after stem cell or bone marrow transplant has
      markedly benefited from the development of new antiviral agents and the use of
      granulocyte/macrophage colony stimulating factors.

PMID- 17035800
TI  - New anti-cancer therapies, new opportunities for infection.
AB  - Therapeutic approaches in the practice of haematology/oncology are increasing in
      complexity. Agents such as the purine analogues and monoclonal antibodies may
      introduce a new spectrum of infection as a consequence of prolonged/profound
      lymphoid suppression. The use of high dose therapy with stem cells support is
      increasing rapidly in clinical practice. Allogeneic transplantation is associated
      with prolonged immunosuppression and a high potential for transplant-related
      mortality from infection. This has led to intense interest in strategies aimed at
      improved prophylaxis and treatment of infective complications. This review aims
      to summarize recent advances in haematological practice and the effect this has
      had on opportunistic infections.

PMID- 17035801
TI  - Infections in solid organ transplant recipients.
AB  - A disturbing trend in evolution for sometime has culminated in the fact that
      resistant Gram-positive bacteria including enterococci and staphylococci have
      emerged as the leading pathogens at many transplant centers. Recently published
      reports have highlighted the formidable challenge such antimicrobial-resistant
      microorganisms now pose in transplant recipients. Studies published within the
      past year have documented the clinical relevance of human herpesvirus-6 after
      transplantation, as well as the transmission of human herpesvirus-8 by
      transplanted allograft and the subsequent development of Kaposi's sarcoma in
      these patients. A novel hepatitis virus has been discovered; studies to elucidate
      its significance in the transplant setting are underway.

PMID- 17035802
TI  - Pneumocystis carinii infection in non-AIDS patients.
AB  - Infection with the opportunist fungus Pneumocystis carinii remains a significant
      cause of morbidity and mortality in non-HIV-infected individuals immunosuppressed
      by a wide range of malignancies, transplantation and inflammatory conditions.
      Glucocorticoid use appears to be an independent risk factor for the development
      of Pneumocystis carinii pneumonia. Transmission from infected to susceptible
      patients may occur, albeit infrequently. A diagnosis of Pneumocystis carinii
      pneumonia may be achieved in the majority of cases by DNA detection using
      polymerase chain reaction on oropharyngeal mouth washes.

PMID- 17035803
TI  - Unusual infections and novel therapy in the immunocompromised host.
AB  - Many of the reports of infection in immunocompromised patients over the past year
      have been caused by unusual bacterial pathogens or fungi, which are often
      multiresistant and difficult to treat. Although many difficulties still remain
      some progress has been made over the past year in the development of new
      antimicrobial agents and alternative therapies.

PMID- 17035804
TI  - Bibliography. Current world literature. Nosocomial and hospital-related
      infections.

PMID- 17035805
TI  - The virtues of epidemiology.

PMID- 17035806
TI  - Recent developments in mycobacterial research.
AB  - Tuberculosis remains a major health problem in the world, which is compounded
      further by the alarmingly high rate of M. tuberculosis infections in AIDS
      patients. Thus, there is an urgent need to advance our understanding of the
      mycobacterium to develop new drugs. The extraordinary recent developments in
      mycobacterial genetic research, particularly in genomics will greatly facilitate
      this goal. The knowledge of the entire genome sequence of M. tuberculosis will
      help in designing new chemotherapeutic and immunotherapeutic interventions. This
      review highlights recent developments in genomics, mycobacterial genetics, novel
      vaccine strategies, and our understanding of tuberculous dormancy.

PMID- 17035807
TI  - Dengue vector surveillance and control.
AB  - This review describes efforts being undertaken to develop new tools and
      strategies to monitor and control dengue fever mosquitoes, mainly Aedes aegypti.
      With the growing realization that the magnitude of the global dengue/dengue
      haemorrhagic fever problem rivals that of malaria and infectious diseases such as
      hepatitis, and that old strategies are unsuitable in today's world, this problem
      requires urgent attention. The new tactics involve proper targeting of important
      breeding sites and diverse control methodologies ranging from biological control
      to molecular transformation of the vectors themselves.

PMID- 17035808
TI  - Travel medicine.
AB  - This review covers significant recent developments in the field of travel
      medicine. New vaccines related to travel are discussed: cholera, Lyme disease,
      and rotavirus. Pertinent travel vaccine-related issues with varicella, polio,
      meningitis, Japanese encephalitis, and tick-borne encephalitis are described. New
      developments in malaria prophylaxis, diagnosis and treatment are discussed.
      Imported cases of African tick bite fever, arboviruses, African trypanosomiasis,
      and Helicobacter pylori, and diarrheal illness are reviewed.

PMID- 17035810
TI  - Gastrointestinal infections: rapid advances in knowledge.

PMID- 17035809
TI  - Gulf War Syndrome: potential role of infectious diseases.
AB  - Following the 1991 war with Iraq, some US, British, and Canadian veterans began
      experiencing diverse symptoms, which have been characterized as a possible 'Gulf
      War Syndrome'. Although veterans have been found to have a variety of illnesses,
      neither the existence nor etiology of a unique syndrome has been confirmed. In
      this review of current literature, the potential for infectious diseases to cause
      health problems nearly a decade after the Gulf War is evaluated.

PMID- 17035811
TI  - Viral gastroenteritis.
AB  - A large number of viruses can be found in the human intestine. Some
      (bacteriophages) infect the bacteria present as normal flora and others use the
      gut as a portal of entry. This review examines the virology, pathogenesis,
      immunology, epidemiology, clinical features, treatment and prevention of the
      viral enteropathogens. Rotavirus is undoubtedly the most important, causing an
      estimated 800,000 deaths each year, especially in developing countries. Recently,
      an oral live quadrivalent rhesus rotavirus vaccine has been licensed for use in
      the USA. It has great potential but there are a number of hurdles to be overcome
      before it can be given to infants in developing countries. Molecular techniques
      are revolutionizing our understanding of rotavirus pathogenesis, and the
      tremendous diversity of Caliciviridae and Astroviridae, as well as producing new
      diagnostic techniques and vaccines.

PMID- 17035812
TI  - Bacterial gut infections.
AB  - Infections of the bowel as a result of bacterial enteropathogens are one of the
      most common medical problems. The use of novel molecular biology techniques and
      the recent development of new antimicrobial drugs and vaccines are helping us to
      identify, understand, treat and prevent these infections.

PMID- 17035813
TI  - Parasitic infections of the intestines.
AB  - Intestinal parasites remain extremely common worldwide. In developing countries,
      intestinal protozoans are important causes of childhood diarrhea.
      Cryptosporidiosis is a common cause of chronic diarrhea in patients with AIDS.
      With the advent of current active antiretroviral therapy the incidence of
      cryptosporidiosis in AIDS has decreased. By contrast, Cryptosporidium,
      Cyclospora, and Giardia outbreaks continue to be associated with contamination of
      food or water. The intestinal helminths Ascaris, hookworm, and Trichuris each
      infects over a thousand million people. While most of those infected experience
      only minor symptoms, recent data highlight subtle effects of parasitism on
      cognitive function and nutrition. Efforts at disease control in developing
      countries are increasingly focused on mass chemotherapy.

PMID- 17035814
TI  - Human microsporidial infection and possible animal sources.
AB  - Sources of human microsporidial infection remain speculative, but possible animal
      reservoirs are emerging. Of the common human microsporidial infections,
      Enterocytozoon bieneusi has now been identified in non-human primates, pigs, dogs
      and a cat; Encephalitozoon intestinalis in dogs, pigs, cows, goats and donkeys
      and Encephalitozoon hellem in budgerigars and parrots. Evidence of species
      heterogeneity is also emerging suggesting that some animal isolates may be
      distinctive. Further molecular epidemiological studies need to be undertaken to
      clarify which animal genotypes can also infect humans. Some of the less common
      microsporidial infections found in humans, such as those involving Pleistophora
      like species, may be the result of infrequent accidental exposure (for example,
      inadequately cooked infected fish muscle) and establishment, particularly if the
      individual is severely immunocompromised.

PMID- 17035816
TI  - Bibliography. Current world literature. Tropical and travel-associated diseases.

PMID- 17035815
TI  - Viral hepatitis.
AB  - Hepatitis A is still the most frequently reported vaccine preventable disease. A
      reduction in the incidence will only be achieved by routine childhood vaccination
      rather than by targeted vaccination of high-risk groups. A larger vaccine program
      is warranted. Hepatitis B remains a large public health problem. Vaccination
      targeted to high-risk adults failed to decrease the incidence of hepatitis B
      virus (HBV) infection. Sexual as well as nosocomial transmission remain serious
      problems. Vaccine escape variants have also been identified in newborns from
      infected mothers who had been vaccinated at birth. Clearance of HBV infection
      results from complex immune mechanisms including TH1 cytokines significantly
      associated with HLA class II alleles. Escape HBV mutants, especially precore
      mutants, influence the outcome. The sequences of the promoter and other critical
      regions were associated with severe activity. Lamivudine is a major advance in
      therapy of chronic hepatitis B which was recently approved in many countries.
      Although drug resistant mutants may be selected during therapy, additional
      nucleoside analogues including adefovir are promising. Optimal combination
      strategies of different active compounds need to be researched. Three per cent of
      the world population has been infected with hepatitis C virus (HCV). Epidemiology
      has shifted from transfusion to non-transfusion settings. Intravenous drug abuse
      is currently the main risk but nosocomial infection is also of concern. Three
      independent factors seem associated with fibrosis progression: age, daily alcohol
      consumption of 50 g or more and male gender. Median duration of progression to
      cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per
      year develop hepatocellular carcinoma. There is little evidence that direct
      cytopathicity plays a significant role in liver cell injury. HCV also infects
      extrahepatic cells which seems critical in the pathogenesis of the many
      extrahepatic manifestations. The recent identification of CD81 protein as one of
      the HCV receptor candidates may help us to understand how chronic HCV infection
      may trigger a wide spectrum of clinical manifestations, autoimmune or even
      lymphoproliferative, through potent continuous B cell activation in the context
      of various host and/or environmental cofactors. Direct measurement of HCV RNA has
      clarified HCV replication kinetics and variability. Among patients with chronic
      hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a
      response rate of 28% among those with genotype 1 and 66% with other genotypes.
      Similar differences were found for combination therapy among patients who had
      relapsed following previous interferon (IFN) therapy. Viral load prior to
      treatment has been clearly shown to be predictive of response to interferon
      treatment, with increased viral load associated with decrease rates of response.
      In patients non-responsive to interferon, a second course of interferon alone has
      no beneficial effect whereas combination therapy may induce response in 25%. In
      conclusion, combination therapy should be given in all situations. Viral
      eradication should not be the only objective of the treatment since histological
      improvement may be obtained despite persisting viral replication with prolonged
      maintenance of antiviral therapy.

PMID- 17035817
TI  - Antibiotic efflux mechanisms.
AB  - Bacterial genomes sequenced to date almost invariably contain genes apparently
      coding for multidrug efflux pumps, and the yeast genome contains more than 30
      putative multidrug efflux genes. Thus it is not surprising that multidrug efflux
      is a major cause of intrinsic drug resistance in many microorganisms, and plays
      an even more prominent role in organisms with a low-permeability cell wall, such
      as Gram negative bacteria in general and Pseudomonas aeruginosa in particular, as
      well as Mycobacterium species. Furthermore, overproduction of intrinsic pumps, or
      acquisition of pump genes from external sources, often results in high levels of
      resistance. This review discusses the classification of efflux proteins, their
      mechanism of action, the regulation of their expression, and the clinical
      significance of efflux pumps.

PMID- 17035818
TI  - The epidemiology of vancomycin-resistant enterococci.
AB  - Major differences in the epidemiology of vanA carrying enterococci exist between
      Europe and the USA, where these organisms have been well investigated. These
      differences are probably related to the differences in antibiotic use in humans
      and animals in both continents, but more research is needed before firm
      conclusions can be drawn.

PMID- 17035819
TI  - The role of quinolones in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease is a disease state characterized by the
      presence of airflow obstruction due to chronic bronchitis and/or emphysema. The
      airflow obstruction is generally progressive. In the past asthma was often
      confused with chronic obstructive pulmonary disease but as the cellular
      inflammatory mechanisms are quite different to chronic bronchitis and emphysema
      it is prudent to separate this condition of airway hyper-responsiveness.
      Exacerbation of chronic obstructive pulmonary disease is a considerable burden on
      health service resources in terms of morbidity and mortality. Approximately one
      half of exacerbations can be attributed to bacterial pathogens, the major
      pathogens being Haemophilus influenzae, Streptococcus pnemoniae and Moraxella
      catarrhalis. Resistance to common first-line treatment antibiotics such as the
      beta-lactams can be variable. Newer fluoroquinolones such as grepafloxacin,
      levofloxacin, sparfloxacin, clinafloxacin, moxifloxacin, gatifloxacin and
      gemifloxacin are characterized by improved activity against Gram positive
      bacteria as well as their Gram negative properties. However, more randomized
      controlled trials need to be accomplished before the true role of quinolones in
      exacerbation of chronic obstructive pulmonary disease is clearly ascertained.

PMID- 17035820
TI  - Antifungal prophylaxis in neutropenia.
AB  - Despite the widespread prophylactic use of antifungal agents in neutropenic
      patients, invasive fungal infections continue to emerge as major causes of
      morbidity and mortality. With the exception of fluconazole prophylaxis in
      allogeneic marrow transplant recipients, no firm conclusions can be drawn due to
      the lack of reliable, randomized trials. At the present time, it seems that
      antifungal chemoprophylaxis is more a matter of faith rather than science.
      Earlier diagnosis based on noninvasive diagnostic techniques and pre-emptive
      strategies may offer more promise than a liberal prophylactic approach.

PMID- 17035821
TI  - Antiparasitic agents: challenges of sleeping sickness, hopes for malaria.

PMID- 17035822
TI  - Recent strategies for the chemotherapy of visceral leishmaniasis.
AB  - Visceral leishmaniasis is a widespread and deadly disease. First-line drugs are
      antimonials, but amphotericin B and its lipid formulations B is used for treating
      visceral leishmaniasis that is unresponsive to antimony. New therapeutic
      approaches are being actively developed, including the following: use of drug
      carriers targeted specifically to the parasite location, thus reduce adverse
      effects of drug; use of immunomodulating drugs; evaluation of natural products;
      pharmacokinetic studies; and drug combinations. Recent clinical trials with
      paromomycin and miltefosine were successful and these drugs appear to be
      promising for the future therapy of visceral leishmaniasis. Furthermore,
      identification and therapeutic evaluation of specific targets in the Leishmania
      organism could lead to new compounds, such as antileishmanial drugs and reversal
      agents of drug resistance.

PMID- 17035823
TI  - The control of the human filariases.
AB  - There is a growing momentum for the global control and elimination of the major
      human filariases as public health problems worldwide. The renewed optimism for
      undertaking this objective reflects the development of simple and potentially
      cost-effective strategies for mass drug delivery in onchocerciasis and the
      availability of new extremely effective drug combinations to treat infection, and
      new methods of morbidity control in lymphatic filariasis. It also reflects the
      development and current availability of very effective diagnostic, surveillance
      and control modeling tools for both parasites. Control programming will also be
      aided by our greater understanding of the biology of transmission, host immunity
      and disease pathogenesis.

PMID- 17035824
TI  - New therapies and changing patterns of treatment for malaria.
AB  - The launch of the Roll Back Malaria initiative by the World Health Organization
      in the period under review confirms malaria's place as one of the great public
      health priorities worldwide. The period 1998-1999 has seen some advances and some
      disappointments in the treatment of malaria, against a backdrop of spreading drug
      resistance. Most encouraging is the clear demonstration that intermittent
      prospective treatment of asymptomatic pregnant women in endemic areas reduces
      morbidity. The greatest disappointment has been the result of trials with the
      artemether-benflumetol fixed-dose combination therapy. Questions have been raised
      about several widely accepted practices, including measurement of quinine levels,
      exchange transfusion, and the prophylactic use of anticonvulsants in children
      with cerebral malaria.

PMID- 17035825
TI  - The potential of adoptive transfer of immunity for reducing post transplant
      Epstein-Barr virus-associated disease.

PMID- 17035826
TI  - Antiretroviral drug level monitoring: the next routine test in HIV management?
AB  - The monitoring of the pharmacokinetics of antiretroviral drugs is sometimes
      thought to be the next routine test in the management of HIV. This overview will
      provide some background information on the subject, and discusses whether there
      is a need for therapeutic drug monitoring for antiretroviral drugs.

PMID- 17035827
TI  - Bibliography. Current world literature. Antimicrobial agents: bacterial/fungal.

PMID- 17035828
TI  - Prostate.

PMID- 17035830
TI  - Surgery, reconstructive surgery.

PMID- 17035831
TI  - Bladder, testicular neoplasm.

PMID- 17035829
TI  - Imaging stone disease.

PMID- 17035833
TI  - Paediatrics andrology, infertility.

PMID- 17035832
TI  - Kidney, transplantation, infections.

PMID- 17035835
TI  - Patient selection: the value of pressure-flow urodynamics.
AB  - Considerable controversy has surrounded the evaluation of men with lower urinary
      tract symptoms and benign prostatic obstruction. Various objective and subjective
      evaluations have been used to aid better patient selection for treatment in order
      to improve outcome. The importance of pressure-flow urodynamics has become better
      appreciated in recent years, although it is plain that the urological community
      is still divided regarding their use.

PMID- 17035836
TI  - Holmium laser prostatectomy: a technique in evolution.
AB  - This review documents the evolution of the current techniques of Holmium:yttrium
      aluminium-garnet (Ho:YAG) laser prostatectomy. An increasing number of centres
      are accumulating experience with this wavelength in the surgical treatment of
      Benign Prostatic Hyperplasia. Newer techniques, including prostatic enucleation
      combined with intracavitary morcellation, are discussed.

PMID- 17035838
TI  - Phytotherapy in the treatment of benign prostatic hyperplasia.
AB  - There are numerous plant extracts that have been used for the treatment of benign
      prostatic hyperplasia and voiding dysfunction. While some extracts show promise,
      their efficacy has not been adequately proven in long-term, double-blind, placebo
      controlled trials. In addition, the mechanism of action remains poorly defined.

PMID- 17035837
TI  - Minimally invasive treatment for benign prostatic hyperplasia.
AB  - The armamentarium of minimally invasive treatment modalities for patients with
      benign prostatic hyperplasia has constantly increased during the past decade. The
      energy sources used range from micro-/radiofrequency waves to high-intensity
      focused ultrasound, laser vaporization/coagulation/resection and electrosurgical
      techniques. Each of these devices has its particular advantages and
      disadvantages. At present, the most intensively studied techniques are
      interstitial laser coagulation, holmium laser resection and new approaches to
      transurethral electrosurgery.

PMID- 17035840
TI  - Epidemiology of chronic prostatitis.
AB  - Although there has been a recent surge of interest in chronic prostatitis, which
      hopefully will translate into advances in our understanding of the distribution
      and determinants of this condition, at present there is a scarcity of published
      epidemiologic research on chronic prostatitis. However, from the currently
      available epidemiologic studies, it appears that chronic prostatitis is common.
      In addition, studies of several determinants (i.e. age, race, region, infectious
      agents, uric acid, sexual activity, autoimmunity, prostate-specific antigen and
      prostate biopsy) may provide clues to the etiology of chronic prostatitis.

PMID- 17035841
TI  - Immunology of chronic prostatitis: etiological and therapeutic considerations.
AB  - Immunological studies of prostatitis have developed from findings of antibody
      coated bacteria in the 1970s to the more recent studies of various models of
      autoimmunity. This review presents data suggesting that possible causes for
      prostatitis (bacterial or otherwise) may be explained under an immunological
      umbrella.

PMID- 17035842
TI  - Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic
      implications.
AB  - Chronic idiopathic prostatitis, sometimes called prostatodynia or abacterial
      prostatitis, is a commonly diagnosed and poorly treated urological syndrome.
      Clinically, this condition frustrates the patient and physician due to its
      chronicity and resistance to therapy. Recent studies suggest that the etiology of
      chronic idiopathic prostatitis may be of bacterial origin. Three types of
      provocative data have demonstrated bacterial presence from prostatic specimens
      (tissue and secretions) that were negative by traditional clinical microbiologic
      tests: (i) presence of bacterial gene sequences in prostatic tissue encoding 16S
      rRNA and tetracycline resistance (tetM-tetO-tetS); (ii) controlled cultural
      findings showing coagulase-negative staphylococci as the most common isolates
      (68%) in prostatodynia (chronic idiopathic prostatitis); and (iii) culture of
      difficult-to-grow coryneforms in expressed prostatic secretions (EPS) on enriched
      culture media and direct microscopic observation of these pleomorphic bacteria in
      EPS. Additionally, earlier experimental studies in a rat model support the
      concept that antibiotic therapy in chronic bacterial prostatitis may not be due
      to altered antibiotic pharmacokinetics in the chronically inflamed prostate
      gland. Rather, ineffective antimicrobial eradication might result from protected
      bacterial micro-colonies within an infection-induced altered micro-environment
      deep within the prostate gland. We postulate that extracellular slime substances
      produced by bacteria that are buried in prostatic tissues could impair host
      defenses by their anti-phagocytic and anti-chemotactic properties that affect
      neutrophils as well as anti-proliferative characteristics that affect
      lymphocytes. These extracellular slime substances could also have cytoprotective
      properties which can conceal bacteria from otherwise bactericidal levels of
      antibiotics and lead to recrudescent infections resistant to therapy. Persistence
      of bacterial antigens might initiate a cascade of cellular immunologic events
      resulting in chronic inflammation of the prostate gland.

PMID- 17035843
TI  - Patient assessment in chronic prostatitis.
AB  - Assessment of men suffering from proven chronic prostatitis involves a cascade of
      diagnostic steps, including evaluation of symptoms and clinical features,
      objectivation of the inflammatory response in expressed prostatic secretions,
      standardized localization techniques for common bacteria and a search for
      fastidious, uncommon pathogens.

PMID- 17035844
TI  - Treatment of chronic prostatitis: an etiologicaly based approach.
AB  - The therapeutics of chronic prostatitis remain as enigmatic as the disease. In
      light of the recent guidelines from the National Institutes of Health, there may
      finally be satisfactory evaluation of efficacy.

PMID- 17035846
TI  - Imaging of renal artery stenosis.
AB  - Renal artery stenosis is the cause of progressive ischemic nephropathy and of
      renovascular hypertension. Due to the invasiveness of arteriography, which is
      claimed to be the gold standard at the present time, several noninvasive imaging
      techniques are available. Colour Doppler sonography is cost-effective, but
      magnetic resonance angiography and computer tomography are more expensive;
      however, both are potential candidates for the definition of a new gold standard.
      Evaluation of renal vasculature by means of Doppler sonography includes intra-
      and extrarenal scanning as well as power Doppler and the use of contrast agents
      for enhancement of the Doppler signals. Computed tomography angiography is a
      minimally invasive method for the diagnosis of renal artery stenosis. There is
      high diagnostic accuracy that is not significantly different from that of
      angiography with respect to main and accessory renal arteries and detection of
      clinically significant renal artery stenoses. The main advantages over
      angiography are the use of an intravenous approach, and direct information
      provided about the vessel wall and adjacent structures. However, the
      nephrotoxicity of contrast material remains a major concern. Magnetic resonance
      angiography of the abdominal aorta and renal arteries has advanced considerably
      over the past few years. Recently developed breath-hold three-dimensional
      magnetic resonance angiography provides a new promising, noninvasive technique to
      evaluate the abdominal aorta and its large branch vessels. Using this technique,
      high sensitivity and specificity is achieved. The improved image quality and the
      ability to detect vascular lesions is due to short acquisition time with
      elimination of respiratory artifacts over an entire imaged volume by single
      breath-hold acquisition. Computed tomography angiography with its fast
      acquisition time and high spatial resolution compares favorably with magnetic
      resonance angiography and colour Doppler sonography. However, as compared with
      Doppler sonography and magnetic resonance angiography, computed tomography
      angiography images display only anatomic information and lack of flow
      sensitivity.

PMID- 17035847
TI  - Detection of recurrent prostate cancer after cryosurgery.
AB  - Cryosurgery is a new method of treating prostate cancer. Long-term results of
      this treatment are not well known. Experience shows that a high percentage of
      patients have detectable prostate-specific antigen within 2 years after therapy,
      which raises the possibility of recurrent disease. The best method for evaluating
      these patients is not yet established. Available diagnostic options are discussed
      and compared.

PMID- 17035848
TI  - Doppler sonography in testicular and scrotal imaging.
AB  - The primary role of Doppler ultrasound of the acute testicle and scrotum is for
      the diagnosis of spermatic cord torsion or epididymitis. The utility of Doppler
      in other conditions such as testicular neoplasm is limited, and in general does
      not increase diagnostic specificity. The application of color Doppler imaging and
      power Doppler imaging increases sensitivity for the detection of orchitis and
      testicular neoplasms in which the gray scale findings may be subtle. Power
      Doppler imaging is more sensitive for the identification of slowly flowing blood
      than color Doppler imaging. As a result, power Doppler imaging may be
      particularly helpful for the diagnosis or exclusion of spermatic cord torsion as
      a cause of acute scrotal pain in the prepubescent male.

PMID- 17035849
TI  - Magnetic resonance imaging of urinary bladder cancer.
AB  - The treatment and prognosis of urinary bladder cancer are largely determined by
      the tumour stage and the presence or not of metastases. Magnetic resonance
      imaging and clinical staging complement each other. Magnetic resonance imaging is
      the most accurate technique for differentiating the various stages of deep tumour
      infiltration and for detecting metastases, whereas clinical staging is the best
      technique for differentiating between post-biopsy effects and the various stages
      of superficial tumours. The role played by magnetic resonance imaging in the
      staging of this disease and the monitoring of therapy is reviewed and
      illustrated. Finally, the authors present an overview of the current and future
      applications of this technique.

PMID- 17035850
TI  - Renal magnetic resonance angiography: an update.
AB  - Recent developments in renal magnetic resonance angiography have led to a
      significant improvement in the technical success rate and diagnostic accuracy of
      the methods. Specifically, three-dimensional contrast-enhanced magnetic resonance
      angiography methods have been shown to provide a more reliable depiction of renal
      artery morphology than older techniques. In addition, recent work has shown that
      variations of magnetic resonance angiography methods have several important
      attributes that may make it feasible to demonstrate the hemodynamic significance
      of a renal artery stenosis. Recent data show that magnetic resonance angiography
      methods may be used to predict patient outcome in response to revascularization
      therapy.

PMID- 17035852
TI  - Renal calculus disease.
AB  - We have seen an explosion in technical innovations for the management of
      urolithiasis. Today, the endourologist possesses an assortment of minimally
      invasive tools to treat renal stones. Most patients receive fast, safe and
      effective treatment in the outpatient setting. Despite the many technical
      advances, however, anatomical malformations and complex stones still provide
      significant challenges in diagnosis, access to a targeted stone, fragmentation,
      and clearance of the resulting fragments. This review examines a variety of
      urinary stone presentations and treatment strategies for cost-effective
      management.

PMID- 17035853
TI  - Obstructive uropathy.
AB  - Recent study has increased the understanding of the physiological processes
      occurring in obstructive uropathy, in particular the role played by vasoactive
      mediators and cellular mechanisms. There is an emphasis on developing effective
      and less invasive means of detection and treatment of ureteric obstruction,
      although it remains to be determined how the techniques currently being assessed
      will impact on clinical practice.

PMID- 17035854
TI  - Renovascular hypertension.
AB  - Renovascular hypertension is the most common cause of secondary hypertension.
      Interest in identifying patients with renal artery stenosis has been stimulated
      recently by advances in three areas. First, is the realization that not only can
      renal artery stenosis cause renovascular hypertension, but it can also lead to
      progressive renal failure (ischemic nephropathy) caused by progression of
      disease, usually atherosclerotic in nature. Second, advances in percutaneous
      transluminal renal angioplasty and, especially, the recent use of renal stents
      has led to a less invasive management of these patients as compared with
      traditional renal revascularization. Finally, the development of newer less
      invasive diagnostic techniques, both for the identification of patients with
      renal artery stenosis and to follow patients with known renal artery stenosis,
      has simplified the diagnostic aspect of the disease.

PMID- 17035855
TI  - Ischemic nephropathy.
AB  - Ischemic nephropathy is an independent pathway towards end-stage renal disease.
      Its prevalence is estimated to be significant and increasing among populations
      with vascular disease, hypertension, and chronic renal failure. Angiography
      remains the gold standard for evaluation of ischemic nephropathy; however,
      selection by clinical criteria and noninvasive screening with ultrasound are
      recommended for most patients. Surgical revascularization of ischemic kidneys can
      halt or reverse deterioration of renal function and is preferable to medical
      treatment. Direct comparison of angioplasty and stent placement with surgery is
      needed.

PMID- 17035856
TI  - Renal transplantation: surgical aspects, complications and results.
AB  - Despite the fact that kidney transplants have routinely been successfully
      performed for over 30 years there continues to be challenges for the transplant
      surgeon. These include a static donor pool, growing recipient list, declining
      number of ideal donors and greater reliance on marginal donors. Innovative
      methods to deal with these problems continue to be sought.

PMID- 17035857
TI  - The modern urologist--still a surgeon?

PMID- 17035858
TI  - Peyronie's disease.
AB  - The pathogenesis of Peyronie's disease is still not well understood. As a result,
      the treatment of Peyronie's disease remains a dilemma and new therapies continue
      to evolve. This article discusses present understanding, controversy and new
      discoveries related to this condition.

PMID- 17035859
TI  - Hypospadias.
AB  - The incidence of hypospadias is increasing. Decreased androgen sensitivity,
      5alpha-reductase deficiency and chromosomal abnormalities are causes of the
      disease. Nonirritant suture material, coverage of the urethral reconstruction by
      additional tissue and perioperative care positively influence the outcome.
      Complication rates after repair of distal hypospadias are low. For severe
      hypospadias staged procedures provide good results. Buccal mucosa is promising
      for initial repair and repeat cases. Psychosocial function in patients with
      severe hypospadias is normal.

PMID- 17035860
TI  - Reconstructive surgery of the upper urinary tract.
AB  - This paper reviews the major publications over the past year regarding upper
      urinary tract reconstruction. Controversies in the diagnosis of ureteropelvic
      junction obstruction and in the surgical repair of the obstructed upper urinary
      tract are discussed. Special emphasis is placed on issues surrounding minimally
      invasive techniques.

PMID- 17035861
TI  - Urologic intestinal reservoirs: the continent outlet.
AB  - General use of standardized terminology and assessment of functional
      characteristics suggested by the International Continence Society will enable
      better comparison of the results and technical specifications of different
      continent outlets. According to the basic functional principle, continence
      mechanisms can be classified into extraluminally and intraluminally located
      continent outlets. Extraluminal continent outlets are easy to construct, but are
      associated with the risk of overflow incontinence. The use of invagination or
      intussusception nipple valves is associated with a long learning curve, tedious
      surgical technique and high complication rate. There is an increasing tendency to
      use the flap valve principle for construction of continent outlets, which
      guarantee a high rate of complete continence with an acceptable complication
      rate.

PMID- 17035863
TI  - Bladder substitution: experimental data.
AB  - Bladder enlargement or substitution using various segments of the
      gastrointestinal tract has been associated with significant metabolic and
      nutritional complications. Extensive research for other alternative materials,
      both synthetic and autologous, has revealed some difficulties including
      rejection, infection and stone formation. Most investigators believe that any
      material used for bladder augmentation must serve as a scaffold for the
      progressive ingrowth of all host bladder wall components, without infection or
      rejection. Recently, acellular matrix has been successfully utilized in
      experimental models for bladder substitution and appeared to satisfy many of
      these prerequisites.

PMID- 17035864
TI  - Tasks of surgical andrology in current interdisciplinary reproductive medicine.
AB  - Although the controversy about varicocele treatment options and their benefit has
      not been resolved, evidence is increasing that a cautious use of varicocele
      surgery contributes to effective management of male factor subfertility.
      Moreover, timely varicocele treatment might be an equally valuable prevention of
      later subfertility as early treatment of cryptorchidism. In reconstructive
      surgery of the ductal system, a more frequent use of tubulovasostomy can prevent
      initial failure. Furthermore, the cryopreservation of spermatic fluid for
      intracytoplasmic sperm injection can obviate a repeat procedure, if patency is
      not reached with surgery. The surgical andrologist is also the 'retriever' of
      sperm cells for assisted reproduction in cases of irreparable damage of the male
      reproductive organs. Efforts to delimit critically the indications and the
      results of the different techniques with large multicentre and interdisciplinary
      studies should be emphasized. Finally, it is encouraging that andrology does not
      rely solely on the successes and possibilities of assisted reproduction, but
      continues to inquire into the causes of male subfertility (e.g. by implementing
      immunohistochemical techniques into clinical research).

PMID- 17035865
TI  - Surgical strategy in late-stage renal cell cancer with intracaval extension.
AB  - During the past two years several reports have substantially contributed to the
      surgical stratification of patients with late-stage renal cell cancer and
      simultaneously occurring intracaval neoplastic extension, and our knowledge about
      the clinical prognosis of the patients after nephrectomy with complete removal of
      the tumour thrombosis has been extended. Recognizing the importance of a
      tolerable perioperative and postoperative morbidity and mortality, it is now well
      documented in the literature that a multidisciplinary approach involving the
      combined use of deep hypothermia, cardiac arrest and cardiopulmonary bypass has
      dramatically improved the feasibility of surgical treatment of the venous
      extension above the hepatic veins. Furthermore, the diagnostic approach for
      patients with intracaval thrombosis, aiming at the reliable delineation of the
      cranial margin of venous extension, has been rationalized without compromising
      important diagnostic information required for the surgical stratification. This
      review assesses the current opinion of the surgical stratification of patients
      with renal cell cancer and intracaval neoplastic extension, the most reliable and
      least invasive diagnostic approach for the preoperative staging and, finally, the
      independent prognostic value of neoplastic venous extension for the clinical
      course of the disease.

PMID- 17035866
TI  - Radical perineal prostatectomy.
AB  - Radical perineal prostatectomy is viewed with increasing favor because prostate
      specific antigen levels now permit exclusion of node dissection. This review
      describes the surgical conduct of the procedure, and notes outcome as a function
      of disease extent.

PMID- 17035867
TI  - Evaluation of catheter loops in central venous port systems.
AB  - OBJECTIVES: We sought to evaluate the cause for catheter loops of central venous
      ports. MATERIAL AND METHODS: A total of 241 patients who received a central
      venous port via subclavian vein access were included in this retrospective study.
      Eighty of these patients had undergone a computed tomography of the chest,
      allowing retrospective evaluation of the course of central venous catheters.
      Complications were evaluated by review of the clinical data charts. RESULTS: In
      49 patients, the catheter penetrated only the major pectoralis muscle. Only one
      of these patients (2.0%) showed a loop. In 31 cases, the catheter went through
      both the major and minor pectoralis muscle, and in 26 of these patients (83.9%),
      a loop was seen. Complications after port implantation were catheter occlusion (n
      = 2), pneumothorax (n = 2), thrombosis (n = 2), infection (n = 1), and catheter
      dislocation (n = 1). CONCLUSIONS: The loop of catheter of central venous ports is
      caused by catheter penetration through pectoralis major and minor.

PMID- 17035868
TI  - Accuracy comparison of a 16 and 64 multidetector-row computed tomography scanner
      to image small high-density structures.
AB  - OBJECTIVES: The accuracy in imaging small high-density structures is compared for
      16 and 64 multidetector-row computed tomography (MDCT) scanners. MATERIALS AND
      METHODS: Phantom experiments and different quantification methods are used to
      establish size measurement accuracy, object signal, and image noise, for both
      MDCT systems. RESULTS: At similar scanning doses, image noise is larger (
      approximately 55%) for the 64 MDCT compared with the 16 MDCT, leading to lower
      signal-to-noise ratios ( approximately 28% for objects <2 mm). Object spread in
      the xy-plane is similar for both systems; while it is reduced along the z-axis
      (by approximately 0.18 mm) for the 64 MDCT. Measurement accuracy of the 64 MDCT
      is not significantly higher (P < 0.05) compared with the 16 MDCT when using a
      relative-threshold corresponding to 50% of the object maximum attenuation value.
      However, when using a fixed-threshold, interscanner and interprotocol measurement
      differences are statistically significant (eg, volume relative errors are reduced
      by approximately 17% on average for the 64 MDCT). CONCLUSIONS: Measurement
      accuracy of the 16 and 64 MDCT scanners is not significantly different when using
      a 50% relative threshold. However, image noise is significantly larger for the 64
      MDCT. Compared with a fixed-threshold based method, the 50% relative-threshold
      strongly reduces interscanner and interprotocol measurement dependency and
      improves accuracy.

PMID- 17035869
TI  - Measurement of coronary artery bifurcation angles by multidetector computed
      tomography.
AB  - OBJECTIVE: Optimal stent deployment in coronary artery bifurcations requires
      information about the angle between main vessel and side branch. We evaluated the
      accuracy and interobserver variability of bifurcation angle measurements by
      contrast-enhanced 16-slice multidetector computed tomography (MDCT) in comparison
      with invasive angiography and examined the average angles of 4 main coronary
      bifurcations. METHODS: To determine the accuracy of MDCT for measurement of
      bifurcation angles, we scanned a coronary artery phantom containing 6
      bifurcations (2-mm metal rods with angles between 25 degrees and 90 degrees )
      using MDCT, and angles determined in the MDCT data set were compared with the
      true values. To assess interobserver variability of angle measurements in
      comparison to invasive angiography, the angles of 3 bifurcation sites (left
      anterior descending and left circumflex coronary artery [LAD/LCX], LAD and first
      diagonal branch [LAD/Diag 1], and posterior descending coronary artery and right
      posterolateral branch [PDA/Rpld]) were determined in 15 patients both in 16
      detector row MDCT data sets and invasive coronary angiograms by 2 independent
      observers each. To assess the natural distribution of the 4 main coronary artery
      bifurcation angles (LAD and LCX, LAD and Diag 1, LCX and OM1, PDA and Rpld), the
      average angles of these bifurcations were determined in 16-slice MDCT data sets
      acquired for coronary artery visalization in a group of 100 consecutive patients
      with suspected coronary artery disease. RESULTS: The phantom study revealed a
      mean difference between measured and true angles of 0.7 +/- 0.5 degrees . In the
      comparison MDCT versus invasive angiography, the 45 angles were significantly
      lager in MDCT (mean: 66 +/- 20 degrees vs. 56 +/- 24 degrees , P = 0.027).
      Interobserver variability was significantly lower in MDCT (r = 0.91) than
      invasive angiography (r = 0.62). Analysis of the natural distribution of
      bifurcation angles by MDCT revealed average values of 80 +/- 27 degrees
      (LAD/LCX), 46 +/- 19 degrees (LAD/Diag1), 48 +/- 24 degrees (LCX/OM1), and 53 +/-
      27 degrees (PDA/Rpld), respectively. CONCLUSION: MDCT allows assessment of
      coronary bifurcation angles with high accuracy, which may be of future potential
      for planning interventional treatment.

PMID- 17035870
TI  - 3 T contrast-enhanced magnetic resonance angiography for evaluation of the
      intracranial arteries: comparison with time-of-flight magnetic resonance
      angiography and multislice computed tomography angiography.
AB  - PURPOSE: We sought to prospectively evaluate the image quality and visualization
      of the intracranial arteries using high spatial resolution contrast-enhanced
      magnetic resonance angiography (CE-MRA) at 3 T and to perform intraindividual
      comparison with time-of-flight (TOF) MRA and multislice CT angiography (CTA).
      MATERIALS AND METHODS: Twelve patients (5 men, 7 women, 37-71 years of age) with
      suspected cerebrovascular disease prospectively underwent MRA and CTA. MRA was
      performed on a 3 T MR system, including both 3-dimensional (3D) TOF (Voxel
      dimension: 0.6 x 0.5 x 0.9 mm in 5 minutes and 40 seconds) and 3D CE-MRA (voxel
      dimension: 0.7 x 0.7 x 0.8 mm in 20 seconds, using parallel acquisition with an
      acceleration factor of 4). CTA images were acquired on a 16-slice CT scanner
      (voxel dimension: 0.35 x 0.35 x 0.8 mm in 17 seconds). The image quality and
      visualization of up to 26 intracranial arterial segments in each study was
      evaluated by 2 experienced radiologists. The arterial diameter for selective
      intracranial arteries was measured independently on each of the 3 studies, and
      statistical analysis and comparative correlation was performed. RESULTS: A total
      of 312 arterial segments were examined by CE-MRA, TOF-MRA, and CTA. The majority
      of intracranial arteries (87%) were visualized with diagnostic image quality on
      CE-MRA with a significant correlation to TOF (R values = 0.84; 95% confidence
      interval 0.79-0.86, P < 0.0001), and to CTA (R values = 0.74; 95% confidence
      interavl 0.68-0.78, P < 0.001). The image quality for small intracranial
      arteries, including the anterior-inferior cerebellar artery, the posterior
      communicating artery, and the M3 branch of the middle cerebral artery, was
      significantly lower on CE-MRA compared with TOF and CTA (P < 0.03). There was a
      significant correlation for the dimensional measurements of arterial diameters at
      CE-MRA with TOF (r = 0.88, 95% confidence interval 0.81-0.93), and CTA (r = 0.83,
      95% confidence interval 0.73-0.90). CONCLUSION: The described 3 T CE-MRA
      protocol, spanning from the cervical to the intracranial vessels, visualized and
      characterized the majority of intracranial arteries with image quality comparable
      with that obtained using TOF-MRA and CTA. Further clinical studies are required
      to establish the accuracy of the technique in a broader clinical setting.

PMID- 17035871
TI  - Quantitative metrics for evaluating parallel acquisition techniques in diffusion
      tensor imaging at 3 Tesla.
AB  - OBJECTIVES: Single-shot echo-planar based diffusion tensor imaging is prone to
      geometric and intensity distortions. Parallel imaging is a means of reducing
      these distortions while preserving spatial resolution. A quantitative comparison
      at 3 T of parallel imaging for diffusion tensor images (DTI) using k-space
      (generalized auto-calibrating partially parallel acquisitions; GRAPPA) and image
      domain (sensitivity encoding; SENSE) reconstructions at different acceleration
      factors, R, is reported here. MATERIALS AND METHODS: Images were evaluated using
      8 human subjects with repeated scans for 2 subjects to estimate reproducibility.
      Mutual information (MI) was used to assess the global changes in geometric
      distortions. The effects of parallel imaging techniques on random noise and
      reconstruction artifacts were evaluated by placing 26 regions of interest and
      computing the standard deviation of apparent diffusion coefficient and fractional
      anisotropy along with the error of fitting the data to the diffusion model
      (residual error). RESULTS: The larger positive values in mutual information index
      with increasing R values confirmed the anticipated decrease in distortions.
      Further, the MI index of GRAPPA sequences for a given R factor was larger than
      the corresponding mSENSE images. The residual error was lowest in the images
      acquired without parallel imaging and among the parallel reconstruction methods,
      the R = 2 acquisitions had the least error. The standard deviation, accuracy, and
      reproducibility of the apparent diffusion coefficient and fractional anisotropy
      in homogenous tissue regions showed that GRAPPA acquired with R = 2 had the least
      amount of systematic and random noise and of these, significant differences with
      mSENSE, R = 2 were found only for the fractional anisotropy index. CONCLUSION:
      Evaluation of the current implementation of parallel reconstruction algorithms
      identified GRAPPA acquired with R = 2 as optimal for diffusion tensor imaging.

PMID- 17035873
TI  - A summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose:
      Phase II and Phase III clinical trials data.
AB  - OBJECTIVE: We sought to summarize the Phase II and Phase III clinical trials
      safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance
      angiography contrast agent. MATERIALS AND METHODS: Subjects with known or
      suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767
      subjects) or placebo (49 subjects) in phase II and phase III studies. Overall
      safety data were pooled from 8 studies and included adverse event monitoring,
      clinical laboratory assays, vital signs, oxygen saturation, physical examination,
      and electrocardiography. The safety was monitored for 72 to 96 hours
      postinjection (PI), and safety comparison with x-ray angiography using iodinated
      contrast media also was performed in 318 subjects. In the phase II trial, 5 doses
      of gadofosveset and placebo were evaluated. In this study, 38 patients were
      administered placebo and 39 patients received 0.03 mmol/kg gadofosveset. RESULTS:
      In pooled data, treatment related adverse events were reported by 176 (22.9%)
      patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In
      phase II trial, treatment-related adverse events were reported by 13 of the 39
      (33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients
      receiving placebo. No severe or serious adverse events were reported in either
      gadofosveset or placebo groups in this phase II trial. Pooled data revealed no
      clinically significant trends in adverse events, laboratory assays, vital signs,
      or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45
      minutes after MS-325 injection; however, this trend was similar to that of the
      placebo group at the same time point (3.2 milliseconds). CONCLUSION: Gadofosveset
      has exhibited a good safety profile and can be safely administered as an
      intravenous bolus injection. The overall rate and experience of adverse events
      was similar to that of placebo. The safety profile of gadofosveset is comparable
      with that of other gadolinium contrast agents as reported in the literature.

PMID- 17035872
TI  - Contrast-induced nephropathy in patients with chronic kidney disease undergoing
      computed tomography: a double-blind comparison of iodixanol and iopamidol.
AB  - BACKGROUND: Based on a single clinical trial, it has been suggested that the
      contrast agent iodixanol, which is isotonic to human plasma, may be less
      nephrotoxic than other nonionic contrast agents in renally impaired patients
      after intra-arterial injection. We compared the effects on renal function of
      iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients
      with chronic kidney disease undergoing contrast-enhanced multidetector computed
      tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized,
      parallel-group design. METHODS: A total of 166 patients with stable moderate-to
      severe chronic kidney disease (screening and baseline serum creatinine, SCr, > or
      =1.5 mg/dL and/or creatinine clearance, CrCl, < or =60 mL/min) who were
      undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive
      equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol
      320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline,
      and at 48-72 +/- 6 hours after dose (mean, 57.4 hours). Contrast-induced
      nephropathy (CIN) was defined as an absolute increase > or =0.5 mg/dL (44.2
      micromol/L) and/or a relative increase in SCr > or =25% from baseline. RESULTS: A
      total of 153 patients were included in the final analysis (13 patients excluded
      because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl
      variation >1% at screening). The 2 study groups were comparable with regard to
      age, gender distribution, the presence of diabetes, concomitant medications,
      hydration, and contrast dose. Mean predose SCr was 1.6 +/- 0.4 mg/dL in both
      groups (P = 0.9). An absolute increase > or =0.5 mg/dL (44.2 micromol/L) in SCr
      was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76)
      of patients receiving iodixanol-320 (95% confidence interval -6.2, 1.0, P = 0.2).
      A relative increase > or =25% in SCr occurred in 4% (3/77) of patients receiving
      iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95%
      confidence interval -6.2, 6.1, P = 1.0). CONCLUSION: The rate of CIN was
      similarly low in risk patients after intravenous administration of iopamidol-370
      or iodixanol-320 for CE-MDCT.

PMID- 17035874
TI  - Operator-dependent reproducibility of size measurements of small phantoms and
      lung nodules examined with low-dose thin-section computed tomography.
AB  - OBJECTIVE: We sought to assess the reproducibility of size measurements of small
      lung nodules examined with low-dose thin-section computed tomography (LDTSCT).
      MATERIALS AND METHODS: Three radiologists measured volume with a semiautomatic
      tool and diameters manually of 20 (equivalent diameter range, 5.3-11 mm) phantom
      nodules and 37 (mean diameter range, 5-8.5 mm) lung nodules in subjects
      undergoing LDTSCT. RESULTS: In phantoms, the worst 95% limits of agreement (95%
      LA) for volume were -3.0% and 3.0% within operator and -3.1% and 2.8% between
      operators. The coefficient of repeatability (CR) for diameter ranged between 0.51
      and 0.67 mm within operator and the 95% LA were from -0.71 to 0.71 mm between
      operators. In nodules, the worst intraoperator 95% LA for volume were -14.4% and
      17.6% within operator and -13.1% and 14.2% between operators. The CR for diameter
      ranged between 0.48 and 0.73 mm within operator and the 95% LA were from -1.16 to
      1.16 mm between operators. CONCLUSION: Operator-dependent variability of size
      measurements of small nodules examined with LDTSCT is not negligible and should
      be considered in lung cancer-screening studies.

PMID- 17035875
TI  - Future nursing administration graduate curricula, Part I: Call to action.

PMID- 17035876
TI  - Expert opinion: challenges and opportunities for academic and organizational
      partnership in evidence-based nursing practice.

PMID- 17035877
TI  - The clinical nurse leader: a valued member of the healthcare team.

PMID- 17035878
TI  - Nurses' perceptions of the advantages and disadvantages of their shift and work
      schedules.

PMID- 17035879
TI  - A new paradigm for information retrieval: InfoButton Access technology.

PMID- 17035880
TI  - A road map for creating a Magnet work environment.
AB  - OBJECTIVE: The authors examine the relationship between working environment and
      the developmental level of the workforce, against the backdrop of the American
      Nurses Credentialing Center Magnet Recognition Program, to provide a road map for
      creating a positive work environment. BACKGROUND: With the daily demands on nurse
      managers, there is a need to identify focused strategies to achieve a Magnetized,
      high-performing work environment. METHODS: The American Nursing Association
      Magnet survey was administered to nurses at a large healthcare system. Patient
      units at each hospital were categorized as reactive, responsive, proactive, or
      high performing. Similar categories of units across all 6 hospitals were
      analyzed. Analysis of variance was performed on each Force of Magnetism by
      developmental level. RESULTS: Mean scores measuring the Forces of Magnetism were
      statistically significant between reactive and responsive units. Likewise, mean
      scores between responsive and proactive units were also statistically
      significant. Between reactive and responsive units, there were 3 statistically
      significant forces of Magnetism: organizational structure, management style, and
      interdisciplinary relations. These are labeled primary priority forces. Between
      responsive and proactive units, there were 6 statistically significant forces of
      Magnetism labeled secondary priority forces: policies and programs; professional
      models of care; quality of care; consultation and resources; autonomy; and
      interdisciplinary relations. CONCLUSIONS: Nursing staff perceive the "Magnetism"
      of the work environment differently, depending on the developmental level of the
      unit. Nurse managers with reactive units should focus on the 3 Forces of
      Magnetism identified as the primary priority forces, in order to help develop
      their unit to the next level of responsive. Once a responsive level has been
      achieved, the next 6 forces should be addressed.

PMID- 17035881
TI  - Improving nursing practice and patient care: building capacity with appreciative
      inquiry.
AB  - Appreciative inquiry is a philosophy and methodology for promoting positive
      organizational change. Nursing leaders at 6 community hospitals are partnering
      with the authors on a project that uses appreciative inquiry to improve
      communication and collaboration, to increase nurse involvement in decision
      making, and to enhance cultural awareness and sensitivity. In this article, the
      authors describe appreciative inquiry, how hospitals are using it, and the
      initial lessons learned.

PMID- 17035882
TI  - Nurse executive and staff nurse perceptions of the effects of reorganization in
      Veterans Health Administration hospitals.
AB  - OBJECTIVE: To examine nurse executive perceptions of effects of service line
      reorganization on nurse executive roles, nursing staff and patient care, and
      compare nurse executive responses to staff nurse reports of job satisfaction and
      quality of care in the same types of Veterans Health Administration facilities.
      BACKGROUND: Although a growing body of research focuses on the association
      between nurse staffing structures, nurse satisfaction, and patient outcomes,
      relatively little attention has been paid to the effects of hospital
      restructuring on nursing management and nursing staff. METHODS: Data on hospital
      and nursing service organization and nurse executive perceptions were collected
      through structured interviews with 125 nurse executives conducted from December
      2002 through May 2003. Staff nurse data were derived from a survey of Veterans
      Health Administration nursing staff conducted from February through June 2003 at
      the same facilities. RESULTS: Nurse executives in Veterans Health Administration
      described significant changes in the nurse executive role, and new challenges for
      managing nursing practice and achieving consistent quality of nursing care.
      Although nursing management perceived differences in the overall effects of
      restructuring on nursing staff depending on the type of reorganization, staff
      nurses reported significant differences in perceived quality of patient care
      across organization types.

PMID- 17035883
TI  - Excellence through evidence: the what, when, and where of clinical autonomy.
AB  - Despite high valuation and persistent challenges to nurses to function
      autonomously, neither the structures fostering clinical autonomy nor the
      relationship between autonomous practice and positive patient outcomes has been
      empirically established. Much of this is caused by the lack of precision in
      definition and measurement of the concept and identification of autonomy-enabling
      structures. The goal of this multisite, evidence-based management practice study
      is to provide an in-depth analysis of the concept and an articulation of a
      grounded theory of clinical autonomy preparatory to the identification of
      structures supporting autonomy. This article describes the research design and
      methodology and explicates the grounded theory by answering the following
      questions: What is clinical autonomy? When and where does it occur? Suggestions
      and recommendations for what could be done to clarify the concept and promote
      clinical autonomy are provided.

PMID- 17035884
TI  - Retaining older nurses in bedside practice.

PMID- 17035886
TI  - Implementation of a written protocol for management of central venous access
      devices: a theoretical and practical education, including bedside examinations.
AB  - The objectives of this study were to evaluate registered nurses' (RN) compliance
      with a local clinical central venous access device (CVAD) protocol after
      completing an educational program and to determine RNs' perception of the
      program. Seventy-five RNs working in hematology participated in the educational
      part of the program. Sixty-eight RNs were examined while changing CVAD dressings
      or placing a Huber needle into a port on actual patients. Sixty percent of the
      RNs passed the examination and reported that the program increased their
      knowledge. The results indicated that the educational program could be
      recommended for use when implementing a new clinical protocol.

PMID- 17035887
TI  - The role of albumin in fluid and electrolyte balance.
AB  - Albumin plays an important role in maintaining homeostasis within the body and
      depends on the cell membrane and the transport mechanism, including diffusion,
      osmosis, filtration, and active transport. The dissolved proteins, which are the
      only substances that do not penetrate the pores of the capillary membrane, are
      responsible for the osmotic pressure of the capillary membrane. Approximately 75%
      of the total colloid osmotic pressure is related to albumin.

PMID- 17035888
TI  - Ethical decision-making when caring for the noncompliant patient.
AB  - Ethical dilemmas frequently occur when nurses care for patients with a history of
      intravenous substance abuse who are hospitalized on medical-surgical units. This
      article discusses the recent findings on substance abuse, including its impact on
      the brain, effects on society and healthcare, available treatment options, and
      medical complications related to substance abuse. An ethical model is introduced
      to analyze ethical dilemmas with an accompanying case scenario. Resources
      available to nursing staff in many healthcare settings are identified as well as
      strategies to improve nursing care for this challenging population. The purpose
      of this article is to reduce nurses' feelings of frustration and stress in order
      to improve their morale. Finally, this particular contemporary ethical issue will
      be viewed as if perceived by Florence Nightingale.

PMID- 17035889
TI  - Vasculitis and biologic infusion therapies: implications for nursing.
AB  - Vasculitis is a heterogeneous group of uncommon, complex rheumatologic diseases.
      These diseases are known for their high mortality and morbidity rates due to the
      underlying disorders themselves, as well as complications of their conventional
      treatments. Oral and intravenous glucocorticosteroids and other immunosuppressive
      agents such as cyclophosphamide, methotrexate, and azathioprine are used to
      manage these diseases. These therapies are effective, but they have a global
      impact (often negative) on patients' immune systems and cause a number of
      nonimmunologic toxicities. They also are ineffective in inducing long-term
      remissions. Novel biologic infusion agents such as rituximab and infliximab are
      being prescribed off-label for some patients with vasculitis who have failed to
      respond to conventional therapy or because there are contraindications to
      standard-of-care treatments. This article provides an orientation to vasculitis,
      its standard of care, infusion biologics under investigation in these diseases,
      and the nursing implications for infusion professionals.

PMID- 17035890
TI  - Update on the management of chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy is associated with a variety of side effects, and many of these can
      be dose-limiting. One of the most dreaded side effects for patients receiving
      chemotherapy is nausea and vomiting, however. Although in the last 2 decades
      there have been several advances in the development of new therapies for
      prevention of chemotherapy-induced nausea and vomiting (CINV), recent
      pharmacologic advances have significantly improved control of this feared side
      effect. Antiemetic guidelines help clinicians manage CINV and are updated
      frequently. Ongoing studies further define appropriate management of patients
      with CINV; of particular interest is delayed nausea and vomiting. With the
      addition of the long-acting serotonin antagonist, palonosetron, and the unique
      neurokinin-1 antagonist, aprepitant, control of CINV has improved considerably
      for those patients receiving chemotherapy. This article discusses CINV and recent
      pharmacologic advances in controlling this side effect. Guidelines for the
      management of CINV are reviewed.

PMID- 17035893
TI  - Youth development is a public health approach. Introduction.

PMID- 17035894
TI  - Healthy youth development: science and strategies.
AB  - Research over the past decade indicates that healthy youth development strategies
      the deliberate process of providing all youth with the support, relationship
      experiences, resources, and opportunities needed to become successful and
      competent adults-are promising approaches for preventing or reducing a wide range
      of adolescent health-risk behaviors. In this article, we describe the history,
      science, and practice of healthy youth development. First, a brief overview of
      barriers to healthy youth development including obstacles the United States will
      face in the coming decades for meetings the needs of all youth is provided. We
      present the history of resiliency research that illuminated the concepts "risk
      factors," "protective factors," and "healthy youth development," and provide
      definitions of each of these concepts. Next, we discuss select empirical evidence
      supporting youth development strategies and highlight the events and experiences
      in the lives of youth that have been consistently shown to protect youth against
      a broad range of health-risk behaviors. Finally, we describe elements of
      effective interventions for promoting the healthy development of all young
      people.

PMID- 17035896
TI  - Management matters: sustaining funds for youth development programs.
AB  - Drawing on data collected through evaluations of youth development (YD) programs,
      including those offered in community-and school-based after-school programs, this
      article describes practices that support program managers' quests for funds that
      will sustain programs. Designing YD activities to incorporate skills building
      (including educational) and recreational and fun activities for adolescents can
      enlarge the resource pool to include funds for educational activities and youth
      engagement. Strong behavioral management of programs encourages youth attendance
      and provides a safe environment to develop positive peer and adult relationships,
      both of which are crucial to YD. Strong attendance, in turn, can keep program
      costs in line with expectations and reduce the marginal costs for additional
      participants. Faithful implementation of previously tested program models
      increases the likelihood that the program will be effective, and positive
      outcomes are essential to sustained funding.

PMID- 17035897
TI  - Youth development as a "big picture" public health strategy.

PMID- 17035898
TI  - Terms of engagement: aligning youth, adults, and organizations toward social
      change.
AB  - Youth engagement is widely accepted as an essential element of successful youth
      development activities at an organizational level. However, because the practical
      issue of how to engage youth in the work of organizations remains unsettled, this
      qualitative research study was conducted as an outgrowth of consultation by Youth
      Infusion (a youth organization that works to support youth as decision makers,
      advocates, and community change agents) requested by two youth-serving
      governmental agencies. Organizational structures, processes, and cultures that
      might support youth engagement were the focus of two research questions: (1) What
      accounts for differences in an organization's youth-adult engagement outcomes;
      and (2) What strategies can organizations adopt to maximize the likelihood of
      successful outcomes? Participatory action research drove the design and
      implementation of data collection and analysis. Five elements were related to
      successful youth engagement: (1) strong external advocacy coalitions; (2)
      alignment of management and staff; (3) clear, consensus-driven visions; (4) an
      openness to change; and (5) unified values. Organizations interested in advancing
      youth engagement in their daily operations should consider attending to these
      elements in their strategic planning.

PMID- 17035899
TI  - Comprehensive statewide approach to improve youth outcomes: experience of the New
      York State Youth Development Team.
AB  - Best practice research indicates a need for a policy shift toward positive youth
      development (YD) principles and strategies. The New York State Youth Development
      Team (YDT) is a public-private partnership of leading agencies whose holistic
      vision, "families, schools and communities partner to support the development of
      healthy, capable and caring youth," requires key stakeholders at all levels to
      address adverse youth health outcomes through effective partnerships. To
      transform the YDT vision into statewide practice requires committed actions
      (policy, funding, and training) at the state and community levels. Key lessons
      learned and experience-based recommendations that guide YD efforts in New York
      State can help state and local agencies move more to a positive YD approach that
      helps young people become healthy, caring, competent, and contributing adults,
      fully prepared to be parents, workers, leaders, entrepreneurs, and citizens of
      the future.

PMID- 17035900
TI  - Adolescent health and youth development: turning social policy into public health
      practice.

PMID- 17035902
TI  - Youth development is a public health approach. Don't make decisions about us,
      without us.

PMID- 17035901
TI  - New York State's "Assets Coming Together (ACT) for Youth": a statewide approach
      effects community change.
AB  - The New York State Department of Health launched an innovative initiative, Assets
      Coming Together (ACT) for Youth, implemented in 2000, as a public health strategy
      to promote youth development (YD) as a means to improve health outcomes for
      youth. ACT for Youth shifted the focus from problems and problem reduction to
      assets and strength-based means of improving health by enhancing opportunities
      and supports in communities for all youth and their families. ACT for Youth is
      innovative in its emphasis on community building and community change at multiple
      levels. This descriptive report mentions development, implementation, specific
      objectives, and highlights of accomplishments in mobilizing communities around
      YD. Lessons learned over the first 5 years of the initiative are reviewed, with
      emphasis on the elements of successful health department YD programming. From
      this foundation, New York State hopes to be in the vanguard of utilizing YD as a
      public health improvement strategy and hopes that others will follow.

PMID- 17035903
TI  - Building effective community partnerships for youth development: lessons learned
      from ACT for Youth.
AB  - Assets Coming Together (ACT) for Youth is a community-based, public health youth
      development (YD) initiative across New York State. Diverse community partnerships
      and a wide range of community settings have participated in this statewide
      effort, providing a rich laboratory to study effective partnership development.
      Based on the experience of the first 6 years of ACT for Youth, this report
      discusses lessons learned in partnership development in ACT for Youth with
      attention to the most effective partnerships. The most effective partnerships
      were differentiated by their ability to accomplish four tasks: (1) clearly define
      the purpose and vision of the initiative, (2) establish a community development
      partnership organizational structure and membership, (3) develop collaborative
      work processes, and (4) create sustained momentum. These elements will receive
      close attention in future YD efforts in New York State, and should be used to
      inform YD efforts in other states or communities.

PMID- 17035904
TI  - Come on back: enhancing youth development through school/community collaboration.
AB  - With the implementation of the federal "No Child Left Behind" Education Act,
      schools in America are under increased pressure to demonstrate academic success
      through higher test scores. Academic leaders are increasingly recognizing that
      the issues that students confront are not unique to the school setting but are
      issues of the larger community. Stronger links need to be forged between those
      working with our youth in schools and those providing needed services in the
      community. The following case study describes "Come On Back," an after-school
      program in Utica, New York, that targets students who are most at risk for
      dropping out of school and experiencing academic failure. The students were
      involved both as participants and planners for Come On Back activities. This
      collaboration applied youth development principles to improve young people's
      connection to school. Come On Back provides an example of how youth development
      partnerships between schools and communities can also be used to improve academic
      performance.

PMID- 17035905
TI  - Capacity-building for youth workers through community-based partnerships.
AB  - Although positive youth development (PYD) is increasingly influential in the
      field of youth programming, core knowledge and competencies for youth workers
      continue to be defined. Youth serving agencies throughout the United States face
      serious obstacles in the creation of a stable and well-trained workforce, despite
      the presence of many talented and resourceful individuals who work with youth in
      the community. One strategy for organizational and staff development is through
      PYD-oriented, community-based partnerships designed to enhance youth worker
      knowledge and competence. Two different partnerships are described in this
      report. The first brought together experts in youth work, health, and trauma, and
      focused on improving youth worker response to psychologic trauma commonly
      experienced by urban youth. This partnership used an iterative reflective
      practice approach to describe best practices in youth work. The second
      partnership strategically taught evaluation skills to youth program consumers,
      AmeriCorps service members, and adult youth workers to advance youth-adult
      partnerships. These exemplars demonstrate that partnerships can drive systems for
      improving competencies in youth workers and the capacities of youth services.

PMID- 17035906
TI  - Youth development and prevention.

PMID- 17035907
TI  - Selecting statewide youth development outcome indicators.
AB  - This article presents the process used to develop a set of statewide positive
      youth development (YD) outcome indicators to complement existing adolescent well
      being indicators in New York State (NYS). Intended uses included program and
      community-, county-, and state-level planning; grant writing; evaluation; and
      outcome monitoring in coordination with national YD-oriented initiatives. A
      common set of metrics, if adopted, would promote consistency and information
      sharing across levels and purposes. A workgroup of the NYS Youth Development Team
      reviewed existing indicators and accepted nominations from NYS stakeholders.
      Input from Youth Development Team members and national YD experts was used to
      narrow the list to 91. Forty-one NYS policy makers performed card sorts and
      ratings of the indicators, and a concept-mapping process, employing hierarchical
      cluster analysis, identified nine clusters of items. The policy makers, along
      with 121 NYS program providers and 91 young adults (aged 18-21) rated the
      indicators from 1 ("not important") to 5 ("very important"). All intergroup
      correlations of ratings were 0.93 or greater, and therefore responses were
      analyzed together. The concept map and mean indicator ratings were used to select
      a short list of 15 indicators. Although respondents were intentionally given a
      mix of problem-focused, risk-focused, and strength-based items, the highest rated
      items were almost exclusively strength based.

PMID- 17035908
TI  - Engaging youth in participatory research and evaluation.
AB  - Although participatory research has been applied by a wide range of disciplines,
      the engagement of youth as partners in research and evaluation efforts is
      relatively new. The positive youth development movement has influenced scholars
      and practitioners to include youth as partners in the design and implementation
      of research involving issues that affect their lives. Engaging youth in research
      and evaluation not only generates useful knowledge for communities and
      individuals but also provides opportunities for the development and empowerment
      of youth participants, leading to benefits for young people, organizations, the
      broader community, and the research process. However, there has been little
      systematic study to establish an evidence base for these effects. This article
      describes four projects that illustrate active youth participation in research.
      These examples demonstrate opportunities for positive youth development, create a
      context for intergenerational partnerships, and generate research findings to
      inform future interventions and organizational improvements, including community
      mobilization.

PMID- 17035909
TI  - Measuring youth development outcomes for community program evaluation and quality
      improvement: findings from Dissemination of the Rochester Evaluation of Asset
      Development for Youth (READY) tool.
AB  - PURPOSE: The Rochester Evaluation of Asset Development for Youth (READY) is a
      brief program-controlled evaluation and quality improvement tool used for
      assessment of four developmental assets for youth: caring adult relationships,
      basic social skills, decision making, and constructive use of leisure time. This
      article reports on the early implementation and combined benchmark data generated
      from the use of the READY tool by community-based youth-serving agencies in
      Rochester, New York. METHODS: Nine youth-serving agencies used the 40-item READY
      tool in 2002-2003. In addition to individual program evaluation and quality
      improvement, a combined dataset was developed and analyzed to establish community
      benchmarks. Program leaders' qualitative feedback on their experience with the
      READY tool is also reviewed. RESULTS: 1,070 youth participated. Those youth who
      reported feeling more connected to the programs in which they participated and
      having more active and frequent participation had consistently higher scores on
      measured outcomes. Overall, most agencies required some technical assistance to
      first field READY. Most agencies successfully used their own data to address
      program quality improvement, and reported being happy with their ability to do
      so. DISCUSSION: READY is a promising tool for measuring community-based program
      attributable positive developmental outcomes for youth.

PMID- 17035910
TI  - Targeting evaluations of youth development-oriented community partnerships.
AB  - Community-based partnerships (CBPs) focused on youth development (YD) have the
      potential to improve public health outcomes. These partnerships also present
      opportunities for the design and implementation of innovative, community-level
      change strategies, which ultimately may result in new capacities for positive YD.
      Evaluation-driven learning and improvement frameworks facilitate the achievement
      of these partnership-related benefits. Partnerships are complex because they
      embody multiple levels of intervention (eg, youth-serving programs, youth
      participation as partners or evaluators, network development for collaborative
      projects and resource sharing, YD-oriented organizational or community policy
      change). This inherent complexity transfers to evaluations of CBPs. This article
      provides resources for meeting evaluation-related challenges. It includes a
      framework for articulating relevant evaluation questions for YD-oriented CBPs, a
      summary of relevant types of evaluation studies, and practical solutions to
      common evaluation problems using targeted evaluation studies. Concrete examples
      of relevant, small-scale evaluation studies are provided throughout.

PMID- 17035913
TI  - The perioperative implications of obstructive sleep apnea.
AB  - Patients with obstructive sleep apnea provide significant challenges to the
      perioperative team. This disorder is often undiagnosed and coexists with other
      disease processes such as hypertension, congestive heart failure, and cor
      pulmonale. The prevalence of obesity in American society suggests that an
      increasing number of patients with sleep apnea will present for surgery. During
      the perioperative period, life-threatening problems can occur during anesthetic
      induction and emergence. The pathophysiology of obstructive sleep apnea is
      reviewed here along with the anesthesia implications of this disease process.
      Members of the perioperative team need to be aware of the implications of sleep
      apnea so that surgical outcomes can be optimized.

PMID- 17035915
TI  - Impact of external fixation on adolescents: an integrative research review.
AB  - PURPOSE: To define the state of nursing knowledge about the psychological impact
      of treating adolescents with external fixation devices (EFDs). METHOD: An
      integrated research review was conducted on literature available from CINAHL,
      MEDLINE, and PsycINFO. Keywords used were external fixation, fracture fixation,
      orthopaedic or orthopaedic, limb lengthening, Ilizarov, halo traction, Orthofix,
      EBI fixator, pelvic fixator, ring fixator, body image, self-concept, self-esteem,
      self-perception, adaptation, emotional, behavior, and outcome. Inclusion criteria
      for studies were (a) publication from 1990 to 2003, (b) focus on psychosocial and
      functional outcomes of treating adolescents with EFDs, and (c) publication in
      English. Studies were categorized by author, year, discipline(s), design, focus,
      sample, measurement, findings, and research recommendations. Findings and
      recommendations were compared across publications. RESULTS: All studies reported
      psychological and behavioral changes after EFD treatment. Pain and pin-site
      infections were the most problematic physical findings. Depression was
      universally evident to varying degrees, with some suicidal ideation and self
      destructive behaviors, although mostly reported as transient. This predominantly
      retrospective cohort of studies reported social isolation as well as eating and
      sleep disturbances. Family and nursing support, a multiple disciplinary approach,
      and better preoperative preparation were crucial to adolescents psychological
      health after EFD treatment. CONCLUSION: Adolescents treated with EFDs require
      significant psychosocial support. The findings reveal major gaps in the knowledge
      on adolescents treated with external fixation for traumatic injury and none
      focused on EFD treatment in the acute period.

PMID- 17035917
TI  - Broken bones: common pediatric upper extremity fractures--part II.

PMID- 17035919
TI  - e-Knee: the electronic knee prosthesis.
AB  - Tibiofemoral forces determine polyethylene wear and affect the longevity of total
      knee prostheses. Previously, investigators relied on theoretic data from
      mathematical models to predict mechanical forces in the knee. Predictions of
      tibiofemoral forces are highly variable because of the complex interplay of the
      muscles involved in activities. Ideally, knee forces should be directly measured.
      An electronic total knee prosthesis (e-Knee) was developed to directly measure
      tibiofemoral compressive and tensile forces in vivo. After 13 years of research
      and development, the e-Knee was implanted into a patient in 2004. Tibiofemoral
      force data were collected intraoperatively and throughout the postoperative
      period during activities of daily living and during exercise. Direct measurement
      of knee forces can lead to a better understanding of the stresses seen following
      total knee arthroplasty. Information generated by the e-Knee will aid in the
      improvement of implant design and patient care.

PMID- 17035921
TI  - Patient Education Corner. Accessing and evaluating the Internet for patient and
      family education.
AB  - In the last decade, the Internet has become a vast resource for healthcare
      information. Multiple Web sites, produced by the federal government, healthcare
      institutions, and individual healthcare providers, give Americans a wealth of
      useful information sources. Nurses recognize that more Americans than ever before
      are using the Internet and that nurses are in an excellent position to help
      patients learn how to search for healthcare topics and evaluate the information
      found. This article will focus on seeking information, judging the quality of the
      information, and listing specific Web sites.

PMID- 17035922
TI  - Managing insomnia.
AB  - Sleep is a vital part of normal health and wellness for everyone. It is also an
      important factor in recovering from the physiological and emotional stress of any
      hospitalization or illness. Insomnia--the lack of adequate period of sleep--has a
      profound impact on society and public health in many ways. Chronic insomnia
      contributes to injury and illness and may have adverse effects on cognitive
      functioning, interpersonal relationships, concentration, the ability to handle
      stress, and productivity. Nurses who are knowledgeable about the possible causes
      of insomnia, the different types of insomnia, and various therapeutic
      interventions will be able to identify those who have insomnia or are at risk of
      insomnia and will be able to counsel these patients about healthy sleep habits
      and the safe use of pharmacotherapeutic therapies used to treat insomnia.

PMID- 17035924
TI  - Osteogenic sarcoma.

PMID- 17035926
TI  - Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity
      limitation--United States, 2003-2005.
AB  - Arthritis is highly prevalent among U.S. adults, the leading cause of disability,
      and associated with substantial activity limitation, work disability, reduced
      quality of life, and high health-care costs. As the population ages, arthritis is
      expected to affect an estimated 67 million adults in the United States by 2030.
      This report updates estimates of the national prevalence of doctor-diagnosed
      arthritis and arthritis-attributable activity limitation in the adult U.S.
      population, using data from the National Health Interview Survey (NHIS) for 2003
      2005. The findings indicated that an estimated 21.6% of the adult U.S. population
      (46.4 million persons) had doctor-diagnosed arthritis, and 8.3% (17.4 million)
      had arthritis-attributable activity limitations. Public and private health
      agencies should promote measures to increase the availability of evidence-based
      arthritis prevention and management interventions.

PMID- 17035927
TI  - Update on vaccine-derived polioviruses.
AB  - In 1988, the World Health Assembly resolved to eradicate polio worldwide. The
      Global Polio Eradication Initiative (PEI) of the World Health Organization (WHO)
      has led to a decline in global polio incidence, from an estimated 350,000 cases
      in 1988 to fewer than 2,000 reported cases in 2005, and polio remains endemic to
      only four countries (Afghanistan, India, Nigeria, and Pakistan). However, two
      additional obstacles to global eradication involve vaccine-derived polioviruses
      (VDPVs). Polio outbreaks continue to be associated with circulating vaccine
      derived polioviruses (cVDPVs) in areas with low oral poliovirus vaccine (OPV)
      coverage. In addition, long-term excretion of neurovirulent immunodeficiency
      associated vaccine-derived polioviruses (iVDPVs) can lead to poliovirus spread to
      contacts. Overcoming these obstacles is challenging. High rates of OPV coverage
      will prevent all poliovirus spread, including spread of VDPVs, but will not
      prevent establishment of prolonged VDPV infections in certain persons with B-cell
      immunodeficiencies (i.e., having defects in antibody production). Inevitable gaps
      in vaccination coverage will give rise to cVDPVs as long as OPV use continues.
      This report updates a previous report on VDPVs and describes the potential
      implications of VDPVs in the final stages of global polio eradication. The
      findings underscore the critical need to strengthen strategies to prevent
      emergence of VDPVs and to stop all OPV use once wild polioviruses (WPVs) are
      eradicated.

PMID- 17035928
TI  - West Nile virus activity--United States, January 1-October 10, 2006.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET as of 3 a.m. Mountain Daylight Time, October 10, 2006. A total of
      41 states and the District of Columbia had reported 3,135 cases of human WNV
      illness to CDC. A total of 1,717 (55%) cases for which such data were available
      occurred in males; median age of patients was 50 years (range: 3 months-99
      years). Dates of illness onset ranged from January 6 to September 25; a total of
      97 cases were fatal.

PMID- 17035929
TI  - Botulism associated with commercial carrot juice--Georgia and Florida, September
      2006.
AB  - On September 8, 2006, the Georgia Division of Public Health (GDPH) and CDC were
      notified of three suspected cases of foodborne botulism in Washington County,
      Georgia. On September 25, the Florida Department of Health and CDC were notified
      of an additional suspected case in Tampa, Florida. This report describes the
      joint investigation and control measures undertaken by state and local health
      departments, CDC, and the Food and Drug Administration (FDA).

PMID- 17035930
TI  - Gestational methylazoxymethanol acetate treatment impairs select cognitive
      functions: parallels to schizophrenia.
AB  - Gestational methylazoxymethanol acetate (MAM) exposure has been suggested to
      produce neural and behavioral abnormalities similar to those seen in
      schizophrenia. In order to assess MAM treatment as a model of schizophrenia,
      pregnant female rats were injected with MAM (22 mg/kg) on gestational day 17 and
      their offspring were assessed in adulthood on a series of cognitive tasks. The
      first experiment involved an attentional set-shifting task, a rodent analog of
      the Wisconsin card sort task. In experiment 2, animals were tested on the 5
      choice serial reaction time task, a rodent analog of the continuous performance
      task. In the final experiment animals were assessed on a differential
      reinforcement of low rate of responding 20 s schedule of reinforcement (DRL-20),
      a task that is sensitive to changes in inhibitory control. In the first
      experiment, MAM-treated animals required a greater number of trials than controls
      to successfully learn an extradimensional shift on the set-shifting task, and had
      difficulties in learning to reverse a previously acquired discrimination. In
      contrast, MAM-treated animals showed little impairment on the 5-choice task,
      aside from a modest but consistent increase in premature responding. Finally, MAM
      exposed animals showed substantial impairments in DRL performance. Post-mortem
      analysis of brain tissue showed significant decreases in tissue weight in the
      hippocampus, parietal cortex, prefrontal cortex, and dorsal striatum of MAM
      treated animals. These results support the notion that MAM treatment may simulate
      some aspects of schizophrenic cognition.

PMID- 17035931
TI  - Enduring deficits in sustained visual attention during withdrawal of intravenous
      methylenedioxymethamphetamine self-administration in rats: results from a
      comparative study with d-amphetamine and methamphetamine.
AB  - Although amphetamine-derived stimulants are widely associated with neurotoxicity,
      it is poorly understood whether extended exposure to such drugs produces lasting
      effects on neurocognitive function. This study investigates whether chronically
      self-administered d-amphetamine, methamphetamine (MA), or
      methylenedioxymethamphetamine (MDMA) leads to residual deficits in a rodent test
      of sustained visual attention and impulsivity. Rats were trained on a five-choice
      serial reaction time task and subsequently trained to self-administer d
      amphetamine, MA, or MDMA (all 50 microg/infusion), intravenously, for 3 weeks.
      Effects on performance were evaluated 24 h after drug discontinuation and for
      several weeks thereafter, including various challenge sessions to increase the
      attentional demands of the task. The results indicate divergent patterns of self
      administration among the three drugs tested with increasing rates of intake
      evident in rats self-administering amphetamine, but not MA, and widely
      fluctuating rates in the MDMA group. Withdrawal of MA resulted in severe
      behavioral disturbances, with significant effects on accuracy, omissions,
      response latency, and impulsivity that lasted up to 2 weeks in some cases.
      Amphetamine and MDMA withdrawal were associated with similar, but shorter-lasting
      effects on performance. However, when challenged with a high event rate session 6
      weeks after drug discontinuation, rats previously exposed to MDMA continued to
      show deficits in the accuracy and speed of responding. These findings show that
      amphetamine-derived stimulants have both short- and long-term consequences for
      psychomotor functioning. The demonstration of residual deficits in rats
      chronically exposed to MDMA raises some concern about the potential harm caused
      by this drug in human ecstasy users.

PMID- 17035932
TI  - Blockade of the mineralocorticoid receptor in healthy men: effects on
      experimentally induced panic symptoms, stress hormones, and cognition.
AB  - Animal studies have shown that blockade of central mineralocorticoid receptors
      (MR) has anxiolytic effects and impairs several aspects of cognitive function. No
      study to date assessed the effects of MR blockade on anxiety and cognitive
      function in humans. In the present study, 16 healthy young men were treated
      either with placebo or with 300 mg spironolactone, a MR-antagonist, at 1100,
      1330, and 1630 hours in a balanced cross-over design with the two study
      conditions being 1 week apart. At 1500 hours, the panic symptoms provoking
      compound cholecystokinin-tetrapeptide (CCK-4) was administered i.v. on both
      occasions and panic symptoms were assessed. We measured plasma ACTH and cortisol
      between 1300 and 1900 hours and assessed cognitive function between 1800 and 1900
      hours. CCK-4 elicited panic symptoms and increased ACTH and cortisol secretion in
      both conditions. Intensity of panic symptoms after CCK-4 was not different
      between spironolactone and placebo. Spironolactone significantly impaired
      selective attention and delayed recall of visuospatial memory, and diminished set
      shifting/mental flexibility on a trend level. Pretreatment with spironolactone
      led to higher baseline cortisol levels compared to placebo whereas no differences
      in stimulated cortisol, baseline ACTH, and stimulated ACTH emerged. Blockade of
      MR with spironolactone increases baseline cortisol secretion and impairs
      cognitive function but has no effect on experimentally induced panic symptoms in
      humans, for the study design and dosage of spironolactone used. The domains of
      cognitive function that are impaired after blockade of MR in men, that is,
      selective attention, visuospatial memory, and mental flexibility/set shifting
      appear to be remarkably similar to those described in animal studies.

PMID- 17035933
TI  - Placebo-controlled trial comparing intermittent and continuous paroxetine in
      premenstrual dysphoric disorder.
AB  - Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously
      to be effective for premenstrual dysphoric disorder (PMDD), but can be given
      during luteal phases only. This is of practical importance, but also of
      theoretical interest since it suggests that the onset of action of SRIs is
      shorter in PMDD than in, for example depression. In this study, both continuous
      and intermittent SRI administration was compared with placebo, with the special
      purpose of analyzing if different PMDD symptoms respond differently depending on
      the treatment regimen. To this end, women meeting slightly modified DSM-IV
      criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three
      menstrual cycles with paroxetine continuously, paroxetine during the luteal phase
      only, or placebo, the population completing at least one treatment cycle
      comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced
      premenstrual symptoms effectively with a response rate of 85%. The effect size
      was highest for irritability (1.4) and lowest for lack of energy (0.5).
      Intermittent treatment was as effective as continuous treatment in reducing
      irritability, affect lability, and mood swings, but had a somewhat weaker effect
      on depressed mood and somatic symptoms. The study indicates that the response
      rate when treating PMDD with SRIs is high, and that irritability is a key target
      symptom. Symptoms such as irritability, affect lability, and mood swings appear
      to be more inclined to respond rapidly to SRIs, enabling intermittent treatment,
      than are, for example, the somatic symptoms.

PMID- 17035934
TI  - Acute effects of atypical antipsychotics on whole-body insulin resistance in
      rats: implications for adverse metabolic effects.
AB  - Although it is generally accepted that atypical antipsychotics differ in their
      risk for diabetic side effects, the underlying pharmacological mechanisms are
      unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or
      insulin resistance are often confounded by the concomitant weight gain and
      dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics
      can acutely cause metabolic effects before any change in body composition, we
      studied the effects of four atypical antipsychotics on whole-body insulin
      resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious
      rats, insulin and somatostatin were infused at a constant rate to provide
      constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose
      was infused at a variable rate, adjusted to maintain euglycemia. At steady state,
      animals were administered vehicle (V) or antipsychotic and the glucose infusion
      rate was monitored as an index of insulin sensitivity. Clamp experiments using
      radiotracers and studies on glucose uptake into isolated skeletal muscle were
      conducted to differentiate between effects on hepatic glucose production (HGP)
      and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely
      impaired whole-body insulin sensitivity in a dose-dependent manner (P<0.001 vs
      V), whereas ziprasidone and risperidone had no effect. CLOZ also induced profound
      insulin resistance after dosing 10 mg/kg/day for 5 days (P<0.05 vs V). Tracer
      studies indicated that acute changes mainly reflect increased HGP, consistent
      with the lack of effect on glucose uptake. OLAN and CLOZ can thus rapidly induce
      marked insulin resistance, which could contribute to the hyperglycemia and
      ketoacidosis reported for patients receiving those therapies.

PMID- 17035935
TI  - The interface of oxytocin-labeled cells and serotonin transporter-containing
      fibers in the primate hypothalamus: a substrate for SSRIs therapeutic effects?
AB  - Oxytocin (OT) is a neuropeptide synthesized in the paraventricular (PVN) and
      supraoptic nuclei (SON) in the hypothalamus. Although OT is more commonly known
      for its role in the milk-ejection reflex, in recent years research has indicated
      that OT participates in the expression of social behavior, memory processing,
      modulation of fear, and stress responses. The demonstration that OT influences
      affiliative behaviors, such as parental care and reproduction, and decreases
      anxiety has lead to speculations that it may have a role in mood disorders.
      Evidence from pharmacologic studies, pointing out the modulation of the OT system
      by serotonin, has argued in favor of OT as a mediator of serotonin reuptake
      inhibitors (SSRIs) antidepressant properties. In the present study, we
      investigated the distribution and overlap of OT-labeled cells and serotonin
      transporter (5-HTT) immunoreactive (IR) fibers in the Macaque hypothalamus,
      utilizing immunocytochemical and double-immunofluorescent techniques. Consistent
      with previous reports, the distribution of OT-labeled cells in the hypothalamus
      is confined to the PVN and SON. In these nuclei, we demonstrate that the
      distribution of 5-HTT-labeled fibers follows the distribution of OT-labeled
      cells. Overlap of OT-labeled neurons and 5-HTT-IR fibers occurs in the
      parvicellular, magnocellular, dorsal, and posterior subdivisions of the PVN. In
      the SON, 5-HTT-labeled fibers and OT-labeled cells overlap in the ventromedial
      subdivision and in the 'capsular' part of the dorsolateral SON. These findings
      provide neuroanatomic support for the idea that SSRIs' therapeutic effects on
      social affiliation and anxiety may be mediated in part through components of the
      OT system.

PMID- 17035936
TI  - Puromycin aminonucleoside induces oxidant-dependent DNA damage in podocytes in
      vitro and in vivo.
AB  - A decline in podocyte number correlates with progression to glomerulosclerosis. A
      mechanism underlying reduced podocyte number is the podocyte's relative inability
      to proliferate in response to injury. Injury by the podocyte toxin puromycin
      aminonucleoside (PA) is mediated via reactive oxygen species (ROS). The precise
      role of ROS in the pathogenesis of PA-induced glomerulosclerosis remains to be
      determined. We sought to examine whether PA-induced ROS caused podocyte DNA
      damage, possibly accounting for the podocyte's inability to proliferate in
      response to PA. In vitro, podocytes were exposed to PA, with or without the
      radical scavenger 1,3-dimethyl-2-thiourea (DMTU). In vivo, male Sprague-Dawley
      rats were divided into experimental groups (n = 6/group/time point): PA, PA with
      DMTU, and control, killed at days 1.5, 3, or 7. DNA damage was measured by DNA
      precipitation, apurinic/apyrimidinic site, Comet, and 8-hydroxydeoxyguanosine
      assays. Cell cycle checkpoint protein upregulation (by immunostaining and Western
      blotting), histopathology, and biochemical parameters were examined. DNA damage
      was increased in cultured podocytes that received PA, but not PA with DMTU. PA
      exposure activated specific cell cycle checkpoint proteins, with attenuation by
      DMTU. DNA repair enzymes were activated, providing evidence for attempted DNA
      repair. The PA-treated animals developed worse proteinuria and histopathologic
      disease and exhibited more DNA damage than the DMTU pretreated group. No
      significant apoptosis was detected by terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling staining. A mechanism underlying the lack of
      podocyte proliferation following PA-induced injury in vitro and in vivo may be
      ROS-mediated DNA damage, with upregulation of specific cell cycle checkpoints
      leading to cell cycle arrest.

PMID- 17035937
TI  - Glomerular involution in children with frequently relapsing minimal change
      nephrotic syndrome: an unrecognized form of glomerulosclerosis?
AB  - Global glomerulosclerosis can be divided in the vascular (obsolescent) type and
      the glomerulopathic (solidified) type. In biopsies from children with recurrent
      nephrotic syndrome owing to minimal change nephropathy (MCN), we noticed small,
      globally sclerosed glomeruli that appeared to be distinct from global
      glomerulosclerosis. These small sclerosed glomeruli are best described as
      involuted glomeruli. We have characterized these involuted glomeruli in detail.
      We studied biopsies of 18 children (11 male, 7 female) with frequently relapsing
      MCN and evaluated possible explanatory variables. The involuted glomeruli can be
      differentiated from the other types of global glomerulosclerosis. Most notable is
      the presence of vital podocytes and parietal epithelial cells, which have
      retained their staining characteristics, in between the matrix, and the absence
      of periglomerular and tubulo-interstitial fibrosis. We observed involuted
      glomeruli in 12 out of 18 biopsies; the median percentage of involuted glomeruli
      was 6% (range 0-33%). The percentage of involuted glomeruli correlated with age
      at renal biopsy and the interval between onset of disease and time of renal
      biopsy, but not with gender, age at onset of disease, or prednisone dose.
      Multivariate analysis revealed that the interval between onset of disease and
      time of renal biopsy was the only independent predictor. In conclusion,
      glomerular involution is a special form of global glomerulosclerosis. The absence
      of periglomerular and tubulo-interstitial fibrosis suggests a different
      pathogenesis. Glomerular involution is a slow process. The clinical data suggest
      that involution is related to the duration of the disease process.

PMID- 17035938
TI  - Membranous and crescentic glomerulonephritis in a patient with anti-nuclear and
      anti-neutrophil cytoplasmic antibodies.

PMID- 17035939
TI  - Very low protein diet supplemented with ketoanalogs improves blood pressure
      control in chronic kidney disease.
AB  - Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We
      compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs
      of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day),
      and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins
      were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110
      consecutive patients; after run-in, they were invited to start VLPD. Thirty
      subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group).
      At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in
      LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower
      in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day,
      respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to
      128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs
      (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly
      correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32
      to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270,
      P<0.0001), BP results independently related to urinary sodium excretion (P=0.023)
      and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in
      moderate to advanced CKD, VLPD has an antihypertensive effect likely due to
      reduction of salt intake, type of proteins, and ketoanalogs supplementation,
      independent of actual protein intake.

PMID- 17035940
TI  - Catch-up growth follows an abnormal pattern in experimental renal insufficiency
      and growth hormone treatment normalizes it.
AB  - The primary goal of this study was to determine if the ability to undergo catch
      up growth following a transient injury is preserved in an experimental model of
      moderate chronic renal failure (CRF) and the effect of growth hormone (GH)
      administration on such phenomenon. Young rats were subtotally nephrectomized
      (days 0 and 4) (Nx). From days 11 to 13, food intake was restricted in subgroups
      of Nx and control (C) rats (NxR and CR). After refeeding, subgroups of NxR and CR
      rats received GH from days 14 to 20 (NxRGH and CRGH). Rats were killed on days 14
      (C, CR, Nx, NxR), 17 and 21 (C, CR, CRGH, Nx, NxR, NxRGH), and 36 (C, CR, Nx,
      NxR). Longitudinal growth rate was measured by osseous front advance in the
      proximal tibiae. With refeeding, growth rate of CR, NxR, and NXrGH rats became
      significantly greater than that of C, indicating catch-up growth. This occurred
      later and with lower growth rate in NxR than in CR rats, whereas the
      characteristics of catch-up growth in CR and NxRGH animals were similar. Changes
      in growth rate were associated with modifications in the morphology and
      proliferative activity of growth cartilage. We conclude that catch-up growth
      occurs in renal insufficiency but follows a different pattern from that observed
      with normal renal function. GH treatment normalizes the pattern of catch-up
      growth in CRF. Changes in growth velocity are associated to modifications in the
      structure and dynamics of growth cartilage.

PMID- 17035941
TI  - IL-1beta induces VEGF, independently of PGE2 induction, mainly through the PI3
      K/mTOR pathway in renal mesangial cells.
AB  - Vascular endothelial growth factor (VEGF) could play a relevant role in
      angiogenesis associated with chronic allograft nephropathy. Interleukin-1beta (IL
      1beta) has a key role in inflammatory response. It induces prostaglandin (PG) E2,
      which is involved in VEGF release by some normal and tumor cells. In the present
      work, we studied the effect of IL-1beta on VEGF release by rat mesangial cells,
      the transduction signal, and whether or not PGE2 is involved in this effect. IL
      1beta induced a time-dependent formation of VEGF (analyzed by enzyme-linked
      immunosorbent assay) and PGE2 (analyzed by enzyme immunoassay). The latter
      correlated with microsomal-PGE-synthase (mPGES)-1 expression rather than with
      cyclooxygenase (COX)-2 in terms of protein, determined by Western blotting. No
      effect of IL-1beta on COX-1, cytosolic PGES, or mPGES-2 expression was observed.
      Indomethacin exerted a nonsignificant effect on IL-1beta-induced VEGF, and
      exogenously added PGE2 exhibited a nonsignificant stimulatory effect on VEGF
      formation. SB 203580, a p38 mitogen-activated protein kinase inhibitor, weakly
      inhibited the induction of VEGF by IL-1beta in a concentration-dependent manner,
      whereas LY 294002, a phosphoinoside 3-kinase (PI3-K) inhibitor, and rapamycin, a
      mammalian target of rapamycin (mTOR) inhibitor, strongly inhibited both IL-1beta-
      and tumor necrosis factor-alpha-induced VEGF formation in a concentration
      dependent manner. Rapamycin also decreased glomerular VEGF levels in the anti
      Thy1.1 model of experimental glomerulonephritis. In conclusion, the PI3-K-mTOR
      pathway seems to be essential in cytokine-induced release of VEGF in mesangial
      cells.

PMID- 17035942
TI  - The urokinase plasminogen activator receptor is crucially involved in host
      defense during acute pyelonephritis.
AB  - The urokinase plasminogen activator receptor (uPAR) is expressed at the cell
      surface of inflammatory cells and plays an important role in neutrophil
      migration. To investigate the in vivo role of uPAR during urinary tract
      infection, acute pyelonephritis was induced in uPAR-/- and wild-type (WT) mice by
      intravesical inoculation with 1 x 10(9) colony-forming units (CFU) of
      uropathogenic Escherichia coli. Mice were killed after 24 and 48 h, after which
      bacterial outgrowth and cytokine levels in kidney homogenates were determined.
      Influx of neutrophils was quantified by myeloperoxidase-enzyme-linked
      immunosorbent assay. uPAR-/- kidneys had significantly higher numbers of E. coli
      CFU, accompanied by higher levels of interleukin-1beta (IL-1beta), IL-6,
      keratinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2),
      and tumor necrosis factor-alpha (TNF-alpha). However, the number of infiltrating
      neutrophils was similar in uPAR-/- and WT mice at both time points, suggesting
      that uPAR-/- neutrophils have a lower ability to eliminate E. coli. To further
      investigate this, neutrophil oxidative burst and phagocytosis was measured. The
      generation of reactive oxygen species upon stimulation with E. coli was not
      diminished in uPAR-/- neutrophils compared with WT. Interestingly, uPAR-/-
      neutrophils displayed significantly impaired phagocytosis of E. coli organisms
      compared with WT neutrophils. We conclude that uPAR is crucially involved in host
      defense through phagocytosis during E. coli induced acute pyelonephritis.

PMID- 17035943
TI  - Methotrexate-associated B-cell lymphoma presenting with acute renal failure and
      bilateral nephromegaly.

PMID- 17035944
TI  - Expression of allograft inflammatory factor-1 in kidneys: A novel molecular
      component of podocyte.
AB  - Our comprehensive gene expression profiles of the kidneys in an anti-glomerular
      basement membrane (GBM) nephritis model using DNA arrays revealed that allograft
      inflammatory factor-1 (AIF-1) was one of the highly expressed genes. Here, we
      explored the pathological significance of AIF-1 expression in the kidneys. The
      expression pattern of AIF-1 mRNA and protein in the kidneys of normal and
      diseased rats, such as anti-GBM nephritis and puromycin aminonucleoside
      nephrosis, was investigated by in situ hybridization, immunohistochemistry, and
      immunoelectron microscopy. Furthermore, the expression of AIF-1 in human kidneys
      and urinary sediments was examined. AIF-1 was expressed at both mRNA and protein
      levels in podocytes of normal and diseased rats, and in infiltrating cells in
      anti-GBM nephritis kidneys. The expression of AIF-1 in podocytes was
      constitutive; positive in podocytes of both normal and diseased rats. In humans,
      AIF-1 was expressed in podocytes and infiltrating inflammatory cells, similarly.
      Moreover, it was detected in urinary podocytes from patients with immunoglobulin
      A nephropathy. These data document for the first time that AIF-1, a
      constitutively expressed protein in rat and human podocytes, is a novel molecular
      component of podocytes, and that the upregulation of AIF-1 in an anti-GBM
      nephritis model may mainly be a consequence of its expression in infiltrating
      cells.

PMID- 17035946
TI  - Lost in publication: Half of all renal practice evidence is published in non
      renal journals.
AB  - Physicians often scan a select number of journals to keep up to date with
      practice evidence for patients with kidney conditions. This raises the question
      of where relevant studies are published. We performed a bibliometric analysis
      using 195 renal systematic reviews. Each review used a comprehensive method to
      identify all primary studies for a focused clinical question relevant to patient
      care. We compiled all the primary studies included in these reviews, and
      considered where each study was published. Of the 2779 studies, 1351 (49%) were
      published in the top 20 journals. Predictably, this list included Transplantation
      Proceedings (5.9% of studies), Kidney International (5.3%), American Journal of
      Kidney Diseases (4.7%), Nephrology Dialysis Transplantation (4.3%),
      Transplantation (4.2%), and Journal of the American Society of Nephrology (2.4%).
      Ten non-renal journals were also on this list, including New England Journal of
      Medicine (2.4%), Lancet (2.3%), and Diabetes Care (2.2%). The remaining 1428
      (51%) studies were published across other 446 journals. When the disciplines of
      all journals were considered, 59 were classified as renal or transplant journals
      (42% of articles). Other specialties included general and internal medicine
      (16%), endocrinology (diabetes) and metabolism (6.5%), surgery (6.2%),
      cardiovascular diseases (6.1%), pediatrics (4.3%), and radiology (3.3%). About
      half of all renal practice evidence is published in non-renal journals. Browsing
      the top journals is important. However, relevant studies are also scattered
      across a large range of journals that may not be routinely scanned by busy
      physicians, and keeping up with this literature requires other continuing
      education strategies.

PMID- 17035945
TI  - Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no
      adverse effects of lanthanum carbonate compared with standard phosphate-binder
      therapy.
AB  - Patients with Stage 5 chronic kidney disease who have hyperphosphatemia require
      treatment with phosphate binders to lower serum phosphorus levels. Existing
      binders are effective but may be associated with important safety disadvantages.
      Lanthanum carbonate is a phosphate binder with demonstrated efficacy, safety, and
      tolerability in clinical trials. Changes in cognitive function were evaluated
      over time using the Cognitive Drug Research computerized cognitive assessment
      system (Simple Reaction Time, Digit Vigilance Task, Choice Reaction Time, Numeric
      Working Memory, and Delayed Picture Recognition) in 360 hemodialysis patients who
      were enrolled in a 2-year, multicenter, comparative study of lanthanum carbonate
      versus standard therapy. A decline in cognitive function from baseline was
      observed in both groups. The deterioration in cognitive function was similar in
      both the lanthanum carbonate and standard therapy groups. One parameter - Numeric
      Working Memory - showed a statistically significant between-group difference in
      favor of lanthanum carbonate (P=0.02). Given the magnitude of the changes,
      however, and the differences that were observed at baseline between treatment
      groups, the clinical significance of this difference is doubtful. This study
      demonstrates that cognitive function deteriorates in hemodialysis patients over a
      2-year time period. Use of lanthanum carbonate as a phosphate binder does not
      adversely affect cognitive function compared with standard therapy.

PMID- 17035947
TI  - BRAVO I: A pilot study of vascular brachytherapy in polytetrafluoroethylene
      dialysis access grafts.
AB  - Hemodialysis vascular access dysfunction owing to stenosis and thrombosis in
      polytetrafluoroethylene dialysis access grafts is a huge clinical problem for
      which there are currently no long lasting durable therapies. Vascular
      brachytherapy has been used successfully for the prevention of coronary
      restenosis following angioplasty and stent placement. The Beta Radiation for
      Treatment of Arterial-Venous Graft Outflow I study was a pilot study of vascular
      brachytherapy in hemodialysis patients with patent but dysfunctional grafts.
      Twenty-five patients were randomized to receive either radiation therapy (a
      single dose of 18.4 Gy) or sham radiation, following angioplasty. The primary
      efficacy end point of the study was target lesion primary patency at 6 months.
      The primary safety end point was a composite of death, emergency surgery on the
      graft, venous rupture, or aneurysm formation. Forty-two percent of the radiated
      grafts achieved the target lesion primary patency end point at 6 months as
      compared to 0% of the control group (P = 0.015), but this did not translate into
      an improvement in secondary patency at either 6 or 12 months. Radiation therapy
      was found to be safe in the setting of hemodialysis vascular access dysfunction.
      Our results suggest that vascular brachytherapy is an intervention that is worthy
      of further examination in the setting of non-thrombosed dialysis access grafts.

PMID- 17035948
TI  - Analysis of fluid transport pathways and their determinants in peritoneal
      dialysis patients with ultrafiltration failure.
AB  - Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis
      (PD). The aim of the study was to analyze changes in water transport and their
      determinants in UFF patients over the time on PD. Standard peritoneal
      permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid
      transport through small pores (SPT), free water transport (FWT) at 60 min, their
      contributions on total ultrafiltration (SPTC and FWTC), and their determinants
      were assessed. Patients were divided in Group I (UFF) treated for less than 24
      months, Group II treated 24-60 months, and Group III treated for more than 60
      months. Group I (UFF) was compared with Group I (non-UFF) matched for the
      duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT,
      FWT, and FWTC were significantly lower in Group III when compared to the other
      UFF groups. In this group also, negative relationship was present between FWT,
      the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one
      hand and PD duration on the other. FWT was positively related to osmotic
      conductance to glucose in all groups. Group I (UFF) showed significantly higher
      solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT
      than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the
      duration of treatment.

PMID- 17035949
TI  - Long-term effects of spironolactone on proteinuria and kidney function in
      patients with chronic kidney disease.
AB  - Experimental evidence suggests that aldosterone contributes to progressive kidney
      disease. Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor
      antagonists suppress the renin-angiotensin system but they do not effectively
      reduce plasma aldosterone. Hence, administration of aldosterone receptor
      antagonists may provide additional renal protection. In the present prospective
      randomized open-label study, we evaluated the effects of spironolactone (25
      mg/day for 1 year) on proteinuria and estimated glomerular filtration rate in 83
      patients with chronic kidney disease already treated with angiotensin-converting
      enzyme inhibitors and/or angiotensin type 1 receptor antagonists. Eighty-two
      patients were treated with angiotensin-converting enzyme inhibitors and/or
      angiotensin type 1 receptor antagonists alone and served as controls. After 1
      year of therapy, proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g
      creatinine (P<0.001) in patients treated with spironolactone, but it did not
      change in control patients. Baseline aldosterone levels were significantly
      correlated with proteinuria (r=0.76, P<0.0001), and predicted the degree of
      reduction in proteinuria with spironolactone (r=0.42, P<0.0002). Baseline
      estimated glomerular filtration rate was similar in patients treated with
      spironolactone and controls (62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2),
      respectively). After 1 month of therapy with spironolactone, estimated glomerular
      filtration rate decreased more in patients treated with spironolactone than in
      controls. However, by the end of 1 year the monthly rate of decrease in estimated
      glomerular filtration rate from baseline was lower in patients treated with
      spironolactone than in controls (0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2),
      P<0.01). Spironolactone caused a significant rise in serum potassium levels (from
      4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment,
      P<0.001). In conclusion, this study has shown that spironolactone may reduce
      proteinuria and retard renal progression in chronic kidney disease patients.

PMID- 17035950
TI  - Ethics of reconstructing Spanish flu: is it wise to resurrect a deadly virus?

PMID- 17035951
TI  - Individual-based assessment of population structure and admixture in Austrian,
      Croatian and German draught horses.
AB  - All over Europe, the number of draught horses has decreased drastically during
      the last 50 years. As a prerequisite for efficient management decisions, we
      analysed the conservation status in Austrian (Noriker Carinthia - NC, Noriker
      Salzburg - NS), Croatian (Croatian Coldblood - C, Posavina horse - P) and German
      (Altmaerkisch Coldblood - A, Black Forest horse - BF, Mecklenburg Coldblood - M,
      Rhenish German Draught horse - R, Saxon Thuringa Coldblood - ST, Schleswig
      Draught horse - Sch, South German Coldblood - SG) draught horses (434) using
      multilocus genotypic information from 30 (effectively 27) microsatellite loci.
      Populations located in areas with less intensive agricultural production (C, NC,
      NS, P and SG) had greater diversity within the population and estimated effective
      population size than A, BF, Sch, M, R and ST populations. The PCA plots revealed
      that populations form five separate groups. The 'Noriker' group (NC, NS and SG)
      and the 'Rhenish' group (A, M, R and ST) were the most distinctive (pairwise
      F(ST) values ranged from 0.078 to 0.094). The 'Croatian' group (C and P) was in
      the centre, while the BF and Sch populations formed two out-groups. A posterior
      Bayesian analysis detected further differentiation, mainly caused by political
      and geographical factors. Thus, it was possible to separate the South German
      Coldblood from the Austrian Noriker population where no subpopulation structure
      was detected. The admixture analysis revealed imprecise classification between C
      and P populations. A small but notable separation of R from A, M and ST
      populations was detected, while Sch and BF populations remained as out-groups.
      The information obtained should aid in making efficient conservation decisions.

PMID- 17035952
TI  - A simple method for detection of imprinting effects based on case-parents trios.
AB  - Using data from families in which marker genotypes are known for the father, the
      mother and the affected offspring, a simple statistic for testing for imprinting
      effects is developed. The statistic considers whether the expected number of
      families in which the father carries more copies of a particular marker allele
      than the mother is equal to the expected number of families in which the mother
      carries more copies of the allele than the father. The proposed parent-of-origin
      effects test statistic (POET) is shown to be normally distributed and can be
      employed to test for imprinting in situations where the marker locus need not be
      a disease susceptibility locus and where the female and male recombination
      fractions are sex-specific. A simulation study is conducted to characterize the
      power of the POET and other properties, and its results show that it is
      appropriate to employ the POET.

PMID- 17035953
TI  - Genetic interactions between the parasitoid wasp Leptopilina boulardi and its
      Drosophila hosts.
AB  - Coevolutionary arms races between hosts and parasites would not occur without
      genetic variation for traits involved in the outcome of parasitism. Genetic
      variations in resistance and virulence have only rarely been described in
      pairwise host-parasitoid interactions and have never been analysed in multi
      species interactions, in contrast to well-characterized plant-pathogen
      interactions. This paper reports genetic variation in resistance of Drosophila
      yakuba to the parasitoid wasp Leptopilina boulardi. The genetic basis and
      geographic distribution of resistance is analysed. On the basis of these and
      previous findings, we demonstrate that there are different resistance patterns to
      the parasitoid species L. boulardi in D. melanogaster and D. yakuba, as well as
      different specificity levels in the parasitoid species, suggesting complex
      ecological interactions in the field. This first description of resistance
      virulence genetic interactions between a parasitoid and its two host species
      provides empirical data showing that multi-species interactions may greatly
      influence coevolutionary processes.

PMID- 17035954
TI  - Cardinium symbionts cause cytoplasmic incompatibility in spider mites.
AB  - Intracellular symbiotic bacteria belonging to the Cytophaga-Flavobacterium
      Bacteroides lineage have recently been described and are widely distributed in
      arthropod species. The newly discovered bacteria, named Cardinium sp, cause the
      expression of various reproductive alterations in their arthropod hosts,
      including cytoplasmic incompatibility (CI), induction of parthenogenesis and
      feminization of genetic males. We detected 16S ribosomal DNA sequences similar to
      those of Cardinium from seven populations of five spider mite species, suggesting
      a broad distribution of infection of Cardinium in spider mites. To clarify the
      effect of Cardinium on the reproductive traits of the infected spider mites,
      infected mites were crossed with uninfected mites for each population. In one of
      the populations, Eotetranychus suginamensis, CI was induced when infected males
      were crossed with uninfected females. The other six populations of four species
      showed no reproductive abnormalities in the F(1) generation, but the possibility
      of CI effects in the F(2) generation remains to be tested. One species of spider
      mite, Tetranychus pueraricola, harbored both Cardinium and Wolbachia, but these
      symbionts seemed to have no effect on the reproduction of the host, even when the
      host was infected independently with each symbiont.

PMID- 17035955
TI  - Evaluating the environmental impact of various dietary patterns combined with
      different food production systems.
AB  - OBJECTIVE: Recent studies support the hypothesis that plant-based diets are
      environmentally better than meat-based diets. This study aims to further explore
      this topic and to compare different environmental impacts resulting from
      different dietary patterns (omnivorous, vegetarian, vegan) and methods of
      production (conventional farming and organic agriculture). DESIGN: Three weekly
      balanced diets, equivalent to one another for energetic and nutrient content,
      have been planned: an omnivorous one, a vegetarian one and a vegan one. For each
      one, the Life Cycle Assessment (LCA) method has been applied in order to
      calculate the environmental impact, expressed in 'points'. INTERVENTIONS: The
      software we selected to carry out the Inventory Analysis and the Impact
      Assessment is SimaPro5. The Assessment phase has been conducted using
      Ecoindicator 99, a damage-oriented method, which analyses the impact according to
      three large damage categories, each of them subsuming various impact categories.

PMID- 17035958
TI  - Forgotten plights.

PMID- 17035959
TI  - A global folly.

PMID- 17035960
TI  - Ambassador for Earth.

PMID- 17035962
TI  - The fizzle heard around the world.

PMID- 17035963
TI  - Protests mount against Libyan trial.

PMID- 17035964
TI  - Intelligent design gets political.

PMID- 17035965
TI  - Nobel prize blurs boundaries.

PMID- 17035966
TI  - Hard-hitting endeavour captures Ig Nobel.

PMID- 17035970
TI  - Hell on no wheels.

PMID- 17035971
TI  - Oceanography: the real sea change.

PMID- 17035972
TI  - AIDS in Africa: a question of trust.

PMID- 17035973
TI  - Depression: comfortably numb.

PMID- 17035975
TI  - Chimp comparisons won't explain human evolution.

PMID- 17035976
TI  - Consistency tests establish empirical generalizations.

PMID- 17035977
TI  - Videos have starring role to play in protocol sharing.

PMID- 17035978
TI  - Biochemistry has outgrown its traditional boundaries.

PMID- 17035984
TI  - Particle physics: did the Big Bang boil?

PMID- 17035985
TI  - Evolutionary biology: fly eyes get the whole picture.

PMID- 17035987
TI  - Physical chemistry: seeds of phase change.

PMID- 17035988
TI  - Developmental biology: a change of heart.

PMID- 17035989
TI  - Neuroscience: controlled capillaries.

PMID- 17035990
TI  - Earth sciences: ups and downs of ancient oxygen.

PMID- 17035991
TI  - Ecology: moving to the ideal free home.

PMID- 17035992
TI  - Cell biology: mitochondria shape up.

PMID- 17035994
TI  - An accessory chromophore in red vision.
AB  - In the absence of a red-sensitive visual pigment, some deep-sea fish use a
      chlorophyll derivative in their green-sensitive rod cells in order to see deep
      red light. Here we show that living rods extracted from a salamander can also
      accumulate an exogenous chlorophyll derivative, chlorin e6, that renders them as
      sensitive to red light as they are to green. This vision enhancement by an
      unbleachable chlorophyll derivative might therefore be a general phenomenon in
      vertebrate photoreception.

PMID- 17035995
TI  - Phosphoinositides in cell regulation and membrane dynamics.
AB  - Inositol phospholipids have long been known to have an important regulatory role
      in cell physiology. The repertoire of cellular processes known to be directly or
      indirectly controlled by this class of lipids has now dramatically expanded.
      Through interactions mediated by their headgroups, which can be reversibly
      phosphorylated to generate seven species, phosphoinositides play a fundamental
      part in controlling membrane-cytosol interfaces. These lipids mediate acute
      responses, but also act as constitutive signals that help define organelle
      identity. Their functions, besides classical signal transduction at the cell
      surface, include regulation of membrane traffic, the cytoskeleton, nuclear events
      and the permeability and transport functions of membranes.

PMID- 17035996
TI  - Role of Bax and Bak in mitochondrial morphogenesis.
AB  - Bcl-2 family proteins are potent regulators of programmed cell death. Although
      their intracellular localization to mitochondria and the endoplasmic reticulum
      has focused research on these organelles, how they function remains unknown. Two
      members of the Bcl-2 family, Bax and Bak, change intracellular location early in
      the promotion of apoptosis to concentrate in focal clusters at sites of
      mitochondrial division. Here we report that in healthy cells Bax or Bak is
      required for normal fusion of mitochondria into elongated tubules. Bax seems to
      induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and
      changing its submitochondrial distribution and membrane mobility-properties that
      correlate with different GTP-bound states of Mfn2. Our results show that Bax and
      Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2
      family members may also regulate apoptosis through organelle morphogenesis
      machineries.

PMID- 17035997
TI  - The sequestration of ethane on Titan in smog particles.
AB  - Saturn's largest satellite, Titan, has a dense atmosphere of nitrogen with a few
      per cent of methane. At visible wavelengths its surface is hidden by dense orange
      brown smog, which is produced in the stratosphere by photochemical reactions
      following the dissociation of methane by solar ultraviolet light. The most
      abundant of the products of these reactions is ethane, and enough of it should
      have been generated over the life of the Solar System to form a satellite-wide
      ocean one kilometre deep. Radar observations have found specular reflections in
      75 per cent of the surface spots observed, but optical searches for a sun-glint
      off an ocean have been negative. Here I explain the mysterious absence or rarity
      of liquid ethane: it condenses onto the smog particles, instead of into liquid
      drops, at the cold temperatures in Titan's atmosphere. This dusty combination of
      smog and ethane, forming deposits several kilometres thick on the surface,
      including the observed dunes and dark areas, could be named 'smust'. This
      satellite-wide deposit replaces the ocean long thought to be an important feature
      of Titan.

PMID- 17035998
TI  - Observation of strong coupling between one atom and a monolithic microresonator.
AB  - Over the past decade, strong interactions of light and matter at the single
      photon level have enabled a wide set of scientific advances in quantum optics and
      quantum information science. This work has been performed principally within the
      setting of cavity quantum electrodynamics with diverse physical systems,
      including single atoms in Fabry-Perot resonators, quantum dots coupled to
      micropillars and photonic bandgap cavities and Cooper pairs interacting with
      superconducting resonators. Experiments with single, localized atoms have been at
      the forefront of these advances with the use of optical resonators in high
      finesse Fabry-Perot configurations. As a result of the extreme technical
      challenges involved in further improving the multilayer dielectric mirror
      coatings of these resonators and in scaling to large numbers of devices, there
      has been increased interest in the development of alternative microcavity
      systems. Here we show strong coupling between individual caesium atoms and the
      fields of a high-quality toroidal microresonator. From observations of transit
      events for single atoms falling through the resonator's evanescent field, we
      determine the coherent coupling rate for interactions near the surface of the
      resonator. We develop a theoretical model to quantify our observations,
      demonstrating that strong coupling is achieved, with the rate of coherent
      coupling exceeding the dissipative rates of the atom and the cavity. Our work
      opens the way for investigations of optical processes with single atoms and
      photons in lithographically fabricated microresonators. Applications include the
      implementation of quantum networks, scalable quantum logic with photons, and
      quantum information processing on atom chips.

PMID- 17035999
TI  - The order of the quantum chromodynamics transition predicted by the standard
      model of particle physics.
AB  - Quantum chromodynamics (QCD) is the theory of the strong interaction, explaining
      (for example) the binding of three almost massless quarks into a much heavier
      proton or neutron--and thus most of the mass of the visible Universe. The
      standard model of particle physics predicts a QCD-related transition that is
      relevant for the evolution of the early Universe. At low temperatures, the
      dominant degrees of freedom are colourless bound states of hadrons (such as
      protons and pions). However, QCD is asymptotically free, meaning that at high
      energies or temperatures the interaction gets weaker and weaker, causing hadrons
      to break up. This behaviour underlies the predicted cosmological transition
      between the low-temperature hadronic phase and a high-temperature quark-gluon
      plasma phase (for simplicity, we use the word 'phase' to characterize regions
      with different dominant degrees of freedom). Despite enormous theoretical effort,
      the nature of this finite-temperature QCD transition (that is, first-order,
      second-order or analytic crossover) remains ambiguous. Here we determine the
      nature of the QCD transition using computationally demanding lattice calculations
      for physical quark masses. Susceptibilities are extrapolated to vanishing lattice
      spacing for three physical volumes, the smallest and largest of which differ by a
      factor of five. This ensures that a true transition should result in a dramatic
      increase of the susceptibilities. No such behaviour is observed: our finite-size
      scaling analysis shows that the finite-temperature QCD transition in the hot
      early Universe was not a real phase transition, but an analytic crossover
      (involving a rapid change, as opposed to a jump, as the temperature varied). As
      such, it will be difficult to find experimental evidence of this transition from
      astronomical observations.

PMID- 17036000
TI  - Origin of the dielectric dead layer in nanoscale capacitors.
AB  - Capacitors are a mainstay of electronic integrated circuits and devices, where
      they perform essential functions such as storing electrical charge, and blocking
      direct current while allowing alternating currents to propagate. Because they are
      often the largest components in circuits, extensive efforts are directed at
      reducing their size through the use of high-permittivity insulators such as
      perovskite-structure SrTiO3 (refs 1, 2), which should provide more capacitance
      per unit area of device. Unfortunately, most experiments on thin-film SrTiO3
      capacitors have yielded capacitance values that are orders of magnitude smaller
      than expected. The microscopic origin of this reduced capacitance, which is often
      discussed in terms of a low-permittivity interfacial 'dead layer', is not well
      understood. Whether such a dead layer exists at all, and if so, whether it is an
      intrinsic property of an ideal metal-insulator interface or a result of
      processing issues such as defects and strains, are controversial questions. Here
      we present fully ab initio calculations of the dielectric properties of realistic
      SrRuO3/SrTiO3/SrRuO3 nanocapacitors, and show that the observed dramatic
      capacitance reduction is indeed an intrinsic effect. We demonstrate the existence
      of a dielectric dead layer by calculating the dielectric profile across the
      interface and analyse its origin by extracting the ionic and electronic
      contributions to the electrostatic screening. We establish a correspondence
      between the dead layer and the hardening of the collective SrTiO3 zone-centre
      polar modes, and determine the influence of the electrode by repeating our
      calculations for Pt/SrTiO3/Pt capacitors. Our results provide practical
      guidelines for minimizing the deleterious effects of the dielectric dead layer in
      nanoscale devices.

PMID- 17036001
TI  - Bistability of atmospheric oxygen and the Great Oxidation.
AB  - The history of the Earth has been characterized by a series of major transitions
      separated by long periods of relative stability. The largest chemical transition
      was the 'Great Oxidation', approximately 2.4 billion years ago, when atmospheric
      oxygen concentrations rose from less than 10(-5) of the present atmospheric level
      (PAL) to more than 0.01 PAL, and possibly to more than 0.1 PAL. This transition
      took place long after oxygenic photosynthesis is thought to have evolved, but the
      causes of this delay and of the Great Oxidation itself remain uncertain. Here we
      show that the origin of oxygenic photosynthesis gave rise to two simultaneously
      stable steady states for atmospheric oxygen. The existence of a low-oxygen (less
      than 10(-5) PAL) steady state explains how a reducing atmosphere persisted for at
      least 300 million years after the onset of oxygenic photosynthesis. The Great
      Oxidation can be understood as a switch to the high-oxygen (more than 5 x 10(-3)
      PAL) steady state. The bistability arises because ultraviolet shielding of the
      troposphere by ozone becomes effective once oxygen levels exceed 10(-5) PAL,
      causing a nonlinear increase in the lifetime of atmospheric oxygen. Our results
      indicate that the existence of oxygenic photosynthesis is not a sufficient
      condition for either an oxygen-rich atmosphere or the presence of an ozone layer,
      which has implications for detecting life on other planets using atmospheric
      analysis and for the evolution of multicellular life.

PMID- 17036002
TI  - Long-period astronomical forcing of mammal turnover.
AB  - Mammals are among the fastest-radiating groups, being characterized by a mean
      species lifespan of the order of 2.5 million years (Myr). The basis for this
      characteristic timescale of origination, extinction and turnover is not well
      understood. Various studies have invoked climate change to explain mammalian
      species turnover, but other studies have either challenged or only partly
      confirmed the climate-turnover hypothesis. Here we use an exceptionally long
      (24.5-2.5 Myr ago), dense, and well-dated terrestrial record of rodent lineages
      from central Spain, and show the existence of turnover cycles with periods of 2.4
      2.5 and 1.0 Myr. We link these cycles to low-frequency modulations of
      Milankovitch oscillations, and show that pulses of turnover occur at minima of
      the 2.37-Myr eccentricity cycle and nodes of the 1.2-Myr obliquity cycle. Because
      obliquity nodes and eccentricity minima are associated with ice sheet expansion
      and cooling and affect regional precipitation, we infer that long-period
      astronomical climate forcing is a major determinant of species turnover in small
      mammals and probably other groups as well.

PMID- 17036003
TI  - Low-coverage vaccination strategies for the conservation of endangered species.
AB  - The conventional objective of vaccination programmes is to eliminate infection by
      reducing the reproduction number of an infectious agent to less than one, which
      generally requires vaccination of the majority of individuals. In populations of
      endangered wildlife, the intervention required to deliver such coverage can be
      undesirable and impractical; however, endangered populations are increasingly
      threatened by outbreaks of infectious disease for which effective vaccines exist.
      As an alternative, wildlife epidemiologists could adopt a vaccination strategy
      that protects a population from the consequences of only the largest outbreaks of
      disease. Here we provide a successful example of this strategy in the Ethiopian
      wolf, the world's rarest canid, which persists in small subpopulations threatened
      by repeated outbreaks of rabies introduced by domestic dogs. On the basis of data
      from past outbreaks, we propose an approach that controls the spread of disease
      through habitat corridors between subpopulations and that requires only low
      vaccination coverage. This approach reduces the extent of rabies outbreaks and
      should significantly enhance the long-term persistence of the population. Our
      study shows that vaccination used to enhance metapopulation persistence through
      elimination of the largest outbreaks of disease requires lower coverage than the
      conventional objective of reducing the reproduction number of an infectious agent
      to less than one.

PMID- 17036004
TI  - Transforming the architecture of compound eyes.
AB  - Eyes differ markedly in the animal kingdom, and are an extreme example of the
      evolution of multiple anatomical solutions to light detection and image
      formation. A salient feature of all photoreceptor cells is the presence of a
      specialized compartment (disc outer segments in vertebrates, and microvillar
      rhabdomeres in insects), whose primary role is to accommodate the millions of
      light receptor molecules required for efficient photon collection. In insects,
      compound eyes can have very different inner architectures. Fruitflies and
      houseflies have an open rhabdom system, in which the seven rhabdomeres of each
      ommatidium are separated from each other and function as independent light
      guides. In contrast, bees and various mosquitoes and beetle species have a closed
      system, in which rhabdomeres within each ommatidium are fused to each other, thus
      sharing the same visual axis. To understand the transition between open and
      closed rhabdom systems, we isolated and characterized the role of Drosophila
      genes involved in rhabdomere assembly. Here we show that Spacemaker, a secreted
      protein expressed only in the eyes of insects with open rhabdom systems, acts
      together with Prominin and the cell adhesion molecule Chaoptin to choreograph the
      partitioning of rhabdomeres into an open system. Furthermore, the complete loss
      of spacemaker (spam) converts an open rhabdom system to a closed one, whereas its
      targeted expression to photoreceptors of a closed system markedly reorganizes the
      architecture of the compound eyes to resemble an open system. Our results provide
      a molecular atlas for the construction of microvillar assemblies and illustrate
      the critical effect of differences in a single structural protein in
      morphogenesis.

PMID- 17036005
TI  - Bidirectional control of CNS capillary diameter by pericytes.
AB  - Neural activity increases local blood flow in the central nervous system (CNS),
      which is the basis of BOLD (blood oxygen level dependent) and PET (positron
      emission tomography) functional imaging techniques. Blood flow is assumed to be
      regulated by precapillary arterioles, because capillaries lack smooth muscle.
      However, most (65%) noradrenergic innervation of CNS blood vessels terminates
      near capillaries rather than arterioles, and in muscle and brain a dilatory
      signal propagates from vessels near metabolically active cells to precapillary
      arterioles, suggesting that blood flow control is initiated in capillaries.
      Pericytes, which are apposed to CNS capillaries and contain contractile proteins,
      could initiate such signalling. Here we show that pericytes can control capillary
      diameter in whole retina and cerebellar slices. Electrical stimulation of retinal
      pericytes evoked a localized capillary constriction, which propagated at
      approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in
      retina or noradrenaline in cerebellum resulted in constriction of capillaries by
      pericytes, and glutamate reversed the constriction produced by noradrenaline.
      Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor
      blockers in the inner retina also evoked pericyte constriction. In simulated
      ischaemia, some pericytes constricted capillaries. Pericytes are probably
      modulators of blood flow in response to changes in neural activity, which may
      contribute to functional imaging signals and to CNS vascular disease.

PMID- 17036006
TI  - Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate
      receptors.
AB  - Feedback inhibition at reciprocal synapses between A17 amacrine cells and rod
      bipolar cells (RBCs) shapes light-evoked responses in the retina. Glutamate
      mediated excitation of A17 cells elicits GABA (gamma-aminobutyric acid)-mediated
      inhibitory feedback onto RBCs, but the mechanisms that underlie GABA release from
      the dendrites of A17 cells are unknown. If, as observed at all other synapses
      studied, voltage-gated calcium channels (VGCCs) couple membrane depolarization to
      neurotransmitter release, feedforward excitatory postsynaptic potentials could
      spread through A17 dendrites to elicit 'surround' feedback inhibitory
      transmission at neighbouring synapses. Here we show, however, that GABA release
      from A17 cells in the rat retina does not depend on VGCCs or membrane
      depolarization. Instead, calcium-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid) receptors (AMPARs), activated by glutamate released
      from RBCs, provide the calcium influx necessary to trigger GABA release from A17
      cells. The AMPAR-mediated calcium signal is amplified by calcium-induced calcium
      release (CICR) from intracellular calcium stores. These results describe a fast
      synapse that operates independently of VGCCs and membrane depolarization and
      reveal a previously unknown form of feedback inhibition within a neural circuit.

PMID- 17036029
TI  - Erythromycin and feeding intolerance in premature infants: a randomized trial.
AB  - OBJECTIVES: To evaluate the effectiveness of low-dose oral erythromycin to treat
      feeding intolerance in preterm infants. DESIGN: This study was a prospective,
      double-blind, randomized, placebo-controlled trial on 60 premature infants
      suffering from feeding intolerance. Thirty infants were given oral erythromycin 1
      mg/kg every 8 h and 30 infants were given placebo (normal saline). Randomization
      was stratified on enrollment according to gestational age whether >32 weeks or
      <or=32 weeks. The primary end point was the length of time taken to establish
      full enteral feeding since enrollment. Potential adverse effects associated with
      erythromycin were also monitored. Groups of each corresponding stratum were
      compared using two-tail t-test and Mann-Whitney for continuous variables, and chi
      (2) and Fisher's exact for categorical variables. RESULTS: For infants with
      gestational age >32 weeks, the erythromycin group achieved full enteral feeding
      earlier than placebo group (10.5+/-4.1 vs 16.3+/-5.7 days, respectively; P=0.01)
      had fewer episodes of gastric residuals (P<0.05) and shorter duration of
      parenteral nutrition (PN) (P<0.05). On the other hand, in infants with
      gestational age <or=32 weeks, there were no significant differences between
      erythromycin and placebo groups regarding any of these variables. CONCLUSION: Low
      dose enteral erythromycin is associated with better tolerance of feeding and
      shorter duration of PN in infants >32 weeks gestation. A similar effect on
      younger preterm infants was not demonstrable.

PMID- 17036007
TI  - Identification of nesfatin-1 as a satiety molecule in the hypothalamus.
AB  - The brain hypothalamus contains certain secreted molecules that are important in
      regulating feeding behaviour. Here we show that nesfatin, corresponding to
      NEFA/nucleobindin2 (NUCB2), a secreted protein of unknown function, is expressed
      in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular
      (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains
      nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is
      decreased in the hypothalamic paraventricular nucleus under starved conditions.
      I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner,
      whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In
      contrast, i.c.v. injection of other possible fragments processed from NUCB2 does
      not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce
      feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight,
      whereas rats gain body weight after chronic i.c.v. injection of antisense
      morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced
      anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti
      nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central
      injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression
      in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an
      antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety
      molecule that is associated with melanocortin signalling in the hypothalamus.

PMID- 17036030
TI  - Gastroschisis in the United States 1988-2003: analysis and risk categorization of
      4344 patients.
AB  - OBJECTIVE: Gastroschisis is a rare congenital abdominal wall defect through which
      intraabdominal organs herniate and it requires surgical management soon after
      birth. The objectives of this study were to profile patient characteristics of
      this anomaly utilizing data from two large national databases and to validate
      previous risk stratification categories of infants born with this condition.
      METHODS: An analysis was performed using 13 years of the National Inpatient
      Sample database (1988-1996, 1998, 1999, 2001, 2002) and 3 years of the Kids'
      Inpatient Database (1997, 2000, 2003). These combined databases contain
      information from nearly 93 million discharges in the United States. Infants with
      gastroschisis were identified by International Classification of Disease-9
      procedure code 54.71 (repair of gastroschisis) and an age at admission of <8
      days. Variables of gender, race, geographic region, co-existing diagnoses, length
      of stay, hospital charges adjusted to 2005 dollars, complications and inpatient
      mortality were collected from the databases. Infants were divided into simple and
      complex categories based on the absence or presence of intestinal atresia,
      stenosis, perforation, necrosis or volvulus. Comparisons between groups were
      performed using Pearson's chi (2) for categorical outcomes and the Kruskal-Wallis
      test for non-normally distributed continuous variables. RESULTS: A total of 4344
      infants with gastroschisis were identified. These were comprised of 44.0% female
      infants (n=1910), 46.4% male infants (n=2017) whereas 9.6% were not reported
      (n=415). Racial analysis showed the largest subset being white in 40.9% of
      infants (n=1775) with Hispanic infants being the next highest group reported at
      17.2% (n=745). Co-existing intestinal anomalies were the most common, affecting
      9.9% (n=429) infants, whereas certain cardiac (6.8%, n=294) and pulmonary (1.7%,
      n=72) conditions were also identified. Simple gastroschisis represented 89.1%
      (n=3870) of the group whereas 10.9% (n=474) were complex in nature. Simple and
      complex patients differed in median length of stay (28 vs 67 days, P<0.01),
      inpatient mortality (2.9 vs 8.7%, P<0.01) and median inflation-adjusted hospital
      charges (90,788 dollars vs 197,871 dollars, P<0.01). CONCLUSIONS: These data
      represent a national analysis of the largest group of infants with gastroschisis
      to date which further aids the characterization and understanding of this serious
      congenital condition.

PMID- 17036031
TI  - Outcomes associated with cesarean section versus vaginal breech delivery at a
      university hospital.
AB  - OBJECTIVE: To determine whether vaginal breech delivery is associated with
      increased morbidity in term breech singletons using strict selection criteria.
      This study encompasses our previous studies (in 1987 and 1995) and extends our
      experience to 21 years. STUDY DESIGN: Retrospective cohort study from 1980 to
      2001 including term, non-anomalous singleton breech deliveries selected by strict
      criteria. Univariable and multivariable analyses were performed for neonatal and
      maternal outcomes. RESULTS: Five hundred and eleven women underwent cesarean
      section and 214 a trial of labor. We found greater overall maternal morbidity in
      the cesarean section group (odds ratio (OR) 1.89, 95% confidence interval
      (CI)=1.34-2.65). In the vaginal delivery group, neonates were more likely to have
      had >1 day of mechanical ventilation (OR 10.0, 95% CI=1.56-63.9). No maternal
      deaths occurred and no neonatal deaths or seizures occurred. CONCLUSION: Given
      our findings, offering a trial of vaginal breech delivery to well-counseled
      strictly selected patients remains an appropriate option.

PMID- 17036032
TI  - Avoiding hyperoxia in infants < or = 1250 g is associated with improved short-
      and long-term outcomes.
AB  - OBJECTIVE: To determine the rate and severity of short- and long-term morbidity
      in very low birth weight infants treated before and after the implementation of a
      change in clinical practice designed to avoid hyperoxia. METHODS: Analysis of a
      prospectively collected database of all infants < or = 1250 g admitted to two
      Emory University NICU's from January 2000 to December 2004. A change in practice
      was instituted in January 2003 with the objective of avoiding hyperoxia in
      preterm infants with target O2 saturation (SpO2) at 93 to 85% (Period II). Before
      the change in practice, SpO2 high alarms were set at 100% and low alarms at 92%
      (Period I). Statistical analysis included bivariate analyses and multivariate
      logistic regression comparing outcomes between the two periods. RESULTS: From
      January 2000 to December 2004, 502 infants met enrollment criteria and 202 (40%)
      were born in period II, after change in SpO2 targets. Birth weight, gestational
      age and survival were similar between both periods. The rates for any retinopathy
      of prematurity, supplemental oxygen at 36 weeks post-conceptional age and the use
      of steroids for chronic lung disease were significantly lower in the infants born
      in Period II. There was no difference in the rates of necrotizing enterocolitis,
      intraventricular hemorrhage and periventricular leukomalacia. At 18 months
      corrected age (CA), the infants treated during Period II had a higher Mental
      Developmental Index (MDI) scores (80.2 +/- 18.3 vs 89.2 +/- 18.5; P 0.02) and
      similar Psychomotor Developmental Index (PDI) scores (83.9 +/- 18.6 vs 89.4 +/-
      17.2; P 0.08) than those treated during Period I. The proportion of infants with
      an MDI or a PDI less than 70 was similar between the periods. CONCLUSIONS: The
      change in practice to avoid hyperoxia is associated with a significant decrease
      in neonatal morbidity and does not have a detrimental effect on developmental
      outcomes at 18 months CA.

PMID- 17036033
TI  - Serum creatinine in very low birth weight infants during their first days of
      life.
AB  - OBJECTIVES: Little is known about the relationship between gestational age (GA)
      or birth weight (BW) and serum creatinine (SCr) in very low birth weight (VLBW)
      infants. We sought to study postnatal SCr changes and determine if there is a
      correlation between GA or BW and SCr in VLBW infants, during their first days of
      life. STUDY DESIGN: Medical records of all VLBW infants, who were admitted to our
      neonatal intensive care unit (NICU) between 1 May 1998 and 1 May 2001, were
      reviewed. Medical records were reviewed for: BW, GA, gender, race, APGAR scores,
      mechanical ventilation, use of medications, fluid intake, urinary output, protein
      intake, blood urea nitrogen (BUN) and SCr during the first days of life. Patients
      with anuria/oliguria, major congenital anomalies, low APGAR scores at 5 min, on
      high ventilator settings (on the oscillator), hemodynamically unstable (on
      pressors, inotropes) and on indomethacin and diuretics were excluded. RESULTS: In
      total, 138 infants met our inclusion criteria. SCr was found to decrease
      postnatally, reaching a plateau on day 5 of life in all VLBW infants (repeated
      measure analysis of variance; P=0.004); however, there was a delay in the
      decrease of SCr in the subgroup of infants <29 weeks GA, and <1000 g BW. SCr (on
      day 5 of life) was also found to decrease with increasing GA and BW (Pearson
      correlation coefficient: -0.206 (P=0.05) and -0.236 (P=0.05) respectively).
      CONCLUSION: In VLBW infants SCr decreases significantly during the first days of
      life; however, in infants younger than 29 weeks GA or smaller than 1000 g BW
      there is a delay in the decrease of their SCr that extends beyond the first days
      of life. We also conclude that during the first days of life, and in VLBW infants
      SCr decreases with advancing GA and BW.

PMID- 17036034
TI  - Low blood neutrophil concentrations among extremely low birth weight neonates:
      data from a multihospital health-care system.
AB  - OBJECTIVE: A blood neutrophil concentration < 1000/microl has been reported to
      occur in about 8% of neonatal intensive care unit (NICU) patients, at some time
      during their hospital stay. However, the incidence of this finding among
      extremely low birth weight (ELBW) neonates (< 1000 g birth weight) is not known.
      Using data from four NICU's in one health-care system, we sought to estimate the
      incidence, timing, causes, severity and duration of neutrophil counts <
      1000/microl among ELBW neonates. We also tabulated the treatments used for this
      condition and associations with mortality. METHODS: We performed an historic
      cohort analysis of all ELBW neonates born during the 36-month period, 1 July 2002
      to 30 June 2005, cared for in the four Intermountain Healthcare level III NICU's.
      RESULTS: Three hundred and thirty-eight ELBW neonates were the subjects of the
      analysis. Complete blood cell counts (CBCs) were obtained in all (range, 1 to 123
      CBCs/patient). Thirty-eight percent (128/338) had one or more neutrophil counts <
      1000/microl. In 57% the low neutrophil count persisted for < 24 h; in 43% it
      persisted for 1 to 7.5 days. Most of the cases (74%) were detected during the
      first 3 days of life. Twenty-two percent of cases were not detected until after
      the first week. Low neutrophil counts were more common among the smallest
      patients, with a 63% incidence in those < or = 500 g, 44% in those 501 to 600 g
      and 34% in those 801 to 999 g. When low neutrophil counts were recognized during
      the first 3 days of life, the patients were typically either small for
      gestational age (SGA; weight < 10th percentile for gestational age) or born after
      pregnancy-induced hypertension (PIH) (68%), or had early-onset bacterial
      infection (6%). When recognized after the first 3 days, the patients typically
      had necrotizing enterocolitis (31%) or a nosocomial bacterial infection (19%).
      Alloimmune mechanisms were not tested for in any of the cases. No cause for the
      low counts was identified among 35% of the neutropenic patients. Intravenous
      immunoglobulins was administered to 28% of cases, and 100% of these were given
      according to our written guidelines. Recombinant granulocyte-colony stimulating
      factor was administered to 13% of cases, and 69% of these were given according to
      guidelines. Neither the presence of low neutrophil counts nor the severity
      (lowest recorded count) correlated with mortality rate, except in proven early
      onset sepsis. CONCLUSIONS: We observed low neutrophil counts among ELBW neonates
      at a rate five times that reported in the general NICU population. Most cases
      were present in the first days of life and occurred in SGA neonates or those with
      PIH. In over 1/3, no cause was discovered. We maintain that more consistency is
      needed in evaluating and treating neutropenia among ELBW neonates.

PMID- 17036035
TI  - Neonatal illicit drug screening practices in Iowa: the impact of utilization of a
      structured screening protocol.
AB  - OBJECTIVE: The purpose of the study was to determine the neonatal illicit drug
      screening practices of Iowa birthing hospitals. STUDY DESIGN: Cross-sectional
      survey design was implemented. The impact of structured screening protocols on
      the numbers of neonates screened and positive testing in 2004 was reviewed.
      RESULTS: Of 81 birthing hospitals, 53 (65%) participated in the study. Screening
      and positive test rates were higher in hospitals utilizing a structured screening
      protocol compared to those not utilizing one (10.9 versus 2.1% and 0.9 versus
      0.2%, respectively, P < 0.0001). Hospitals with higher population, numbers of
      outpatients, inpatients, deliveries, and availability of drug abuse treatment
      services utilized a structured screening protocol more often. CONCLUSION:
      Utilization of a structured screening protocol increases the number of neonates
      screened for illicit drugs and positive testing rate regardless of urbanization.
      Regional standardization of structured screening protocols may improve the
      recognition of perinatal illicit drug exposure and provision of treatment
      services.

PMID- 17036037
TI  - Guido Fanconi (1892-1979): a jack of all trades.
AB  - In 1927 the Swiss paediatrician Guido Fanconi described a family in which three
      boys had physical birth defects and died of a condition that resembled pernicious
      anaemia. In the 1960, inspired by Fanconi's theoretical considerations, it was
      shown that the disorder is based on an underlying chromosomal instability and is
      associated with a predisposition to bone marrow failure and cancer. As the 80th
      anniversary of the first description of Fanconi anaemia approaches, we were
      motivated to pay tribute to Guido Fanconi as an outstanding figure in European
      medicine and to honour his contribution to cancer research.

PMID- 17036038
TI  - Selecting targets for cancer prevention: where do we go from here?
AB  - Given the lack of progress in curing metastatic epithelial cancers, there is
      intense interest in, and a sound scientific rationale for, pursuing strategies to
      prevent cancer. However, although several clinical trials have shown efficacy in
      cancer prevention, few have resulted in changes to medical practice, and some
      trials have even shown harm. Recent experiences with serious side effects
      identified in cancer prevention trials underscore the need to re-evaluate our
      approach to clinical chemopreventive drug development, and to establish a
      framework for agent selection for future trials.

PMID- 17036039
TI  - Breast cancer treatment and ovarian failure: risk factors and emerging genetic
      determinants.
AB  - Most premenopausal women diagnosed with primary breast cancer receive adjuvant
      chemotherapy, and many experience chemotherapy-induced ovarian failure (CIOF).
      CIOF is associated with menopausal symptoms, fertility concerns and long-term
      implications including bone loss. Ironically, CIOF might confer a disease
      specific benefit to women whose breast cancers express hormone receptors. Risk
      factors of CIOF include the woman's age at the time of therapy, and the type,
      dose and schedule of chemotherapy. Because inherited genetic factors have an
      important role in determining who will experience CIOF, genetic testing has the
      potential to provide optimal counselling about risks and possible interventions.

PMID- 17036040
TI  - The multifaceted circulating endothelial cell in cancer: towards marker and
      target identification.
AB  - Increases in the number of circulating endothelial cells (CECs) and progenitors
      (CEPs) have been reported in various pathological conditions including cancer.
      Preclinical studies have shown that CEC and CEP kinetics correlate well with
      several standard laboratory angiogenesis assays, which cannot be used in humans.
      At the clinical level, evidence is emerging that CEC kinetics and viability might
      correlate with clinical outcomes in cancer patients who undergo anti-angiogenic
      treatment. Therefore, CEC and CEP measurement has potential as a surrogate marker
      for monitoring anti-angiogenic treatment and drug activity, and could help to
      determine the optimal biological dose of anti-angiogenic drugs, which are being
      used with increasing frequency in medical oncology.

PMID- 17036041
TI  - Integration of EGFR inhibitors with radiochemotherapy.
AB  - Laboratory studies that led to the development of epidermal growth factor
      receptor (EGFR) inhibitors indicated that such inhibitors would be effective when
      given to patients with tumours that are driven by activated EGFR. However,
      initial clinical studies have shown modest responses to EGFR inhibitors when used
      alone, and it has not yet been possible to clearly identify which tumours will
      respond to this therapy. As a result, EGFR inhibitors are now used in combination
      with radiation therapy, chemotherapy and, more recently, with concurrent
      radiochemotherapy. In general, these clinical trials have been designed without
      much preclinical data. What do we need to know to make these combinations
      successful in the clinic?

PMID- 17036042
TI  - Use of antihypertensive and lipid-lowering drugs: the management of
      cardiovascular risk in clinical practice.
AB  - The objective of the study was to analyse the treatment of high blood pressure
      (BP) and hypercholesterolaemia, as well as the effect of individual or combined
      antihypertensive-hypocholesterolaemic therapy on BP control and on circulating
      cholesterol. A retrospective study was performed using clinical data recorded in
      the general practitioner's database. The sample included all patients, aged > or
      =18 years, with BP reading or low-density lipoprotein (LDL) cholesterol
      measurement recorded between January 2003 and December 2004. BP and LDL
      cholesterol targets were defined using cutoffs based on the guidelines of the
      Joint National Committee on Prevention, Detection, Evaluation and Treatment of
      High Blood Pressure (JNC7) and the National Cholesterol Education Program
      (NCEP/ATPIII). The study included 4764 patients (mean age 67.6+/-11.8 years,
      43.5% males). Target BP was achieved in a higher number of patients under
      combined antihypertensive-hypocholesterolaemic therapy than in those treated only
      with antihypertensives: 57.0 vs 50.0% in patients with history of
      cardio/cerebrovascular (CV) hospitalization, 27.0 vs 16.9% in patients with
      diabetes or chronic renal insufficiency (CRI) and 59.7 vs 49.1% in patients with
      no CV hospitalization nor diabetes and nor CRI. The LDL cholesterol target was
      achieved in 61.3% of the subjects: it was independent on the therapy (individual
      or combined), but related to the degree of cardiovascular risk. Analysing the
      data contained in the general medicine database made it possible to evaluate the
      treatment of high BP and hypercholesterolaemia in relation to cardiovascular risk
      in clinical practice and to establish the need to pay greater attention to
      achieving the objective set by guidelines.

PMID- 17036043
TI  - Prevalence and clinical implications of the inter-arm blood pressure difference:
      A systematic review.
AB  - A blood pressure (BP) difference between arms was first reported over 100 years
      ago. Knowledge of its prevalence and relevance to the accurate measurement of BP
      remains poor. Current hypertension guidelines do not emphasise it. The objectives
      of this study were to establish the best estimate of prevalence of the inter-arm
      difference (IAD) in the population, to consider its implications for accurate BP
      measurement and treatment, and to discuss its aetiology and potential as a risk
      marker for cardiovascular disease. Systematic literature review was carried out.
      The data sources were Medline EMBASE and CINAHL databases, and Index of Theses.
      Studies reporting prevalence rates of IAD were retrieved and considered for
      inclusion against explicit methodological criteria. Point prevalence rates were
      extracted and weighted mean prevalence rates calculated. The main outcome
      measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm
      Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most
      had methodological weaknesses; only four met the inclusion criteria. Pooled
      prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg
      (95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1%
      diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a
      substantial number of patients and should be looked for whenever diagnosis and
      treatment depend on accurate measurements of BP. The importance of an IAD should
      be better emphasised in current hypertension management guidelines. There is
      evidence associating an IAD with peripheral vascular disease, raising the
      possibility that its presence may predict cardiovascular events.

PMID- 17036044
TI  - Molecular basis of RNA recognition and TAP binding by the SR proteins SRp20 and
      9G8.
AB  - The sequence-specific RNA-binding proteins SRp20 and 9G8 are the smallest members
      of the serine- and arginine-rich (SR) protein family, well known for their role
      in splicing. They also play a role in mRNA export, in particular of histone
      mRNAs. We present the solution structures of the free 9G8 and SRp20 RNA
      recognition motifs (RRMs) and of SRp20 RRM in complex with the RNA sequence
      5'CAUC3'. The SRp20-RNA structure reveals that although all 4 nt are contacted by
      the RRM, only the 5' cytosine is primarily recognized in a specific way. This
      might explain the numerous consensus sequences found by SELEX (systematic
      evolution of ligands by exponential enrichment) for the RRM of 9G8 and SRp20.
      Furthermore, we identify a short arginine-rich peptide adjacent to the SRp20 and
      9G8 RRMs, which does not contact RNA but is necessary and sufficient for
      interaction with the export factor Tip-associated protein (TAP). Together, these
      results provide a molecular description for mRNA and TAP recognition by SRp20 and
      9G8.

PMID- 17036045
TI  - An extended consensus motif enhances the specificity of substrate modification by
      SUMO.
AB  - Protein modification by SUMO conjugation is an important regulatory event.
      Sumoylation usually takes place on a lysine residue embedded in the core
      consensus motif psiKxE. However, this motif confers limited specificity on the
      sumoylation process. Here, we have probed the roles of clusters of acidic
      residues located downstream from the core SUMO modification sites in proteins
      such as the transcription factor Elk-1. We demonstrate that these are
      functionally important in SUMO-dependent transcriptional repression of Elk-1
      transcriptional activity. Mechanistically, the acidic residues are important in
      enhancing the efficiency of Elk-1 sumoylation by Ubc9. Similar mechanisms operate
      in other transcription factors and phosphorylation sites can functionally
      substitute for acidic residues. Thus, an extended sumoylation motif, termed the
      NDSM (negatively charged amino acid-dependent sumoylation motif), helps define
      functional SUMO targets. We demonstrate that this extended motif can be used to
      correctly predict novel targets for SUMO modification.

PMID- 17036046
TI  - Six2 is required for suppression of nephrogenesis and progenitor renewal in the
      developing kidney.
AB  - During kidney development and in response to inductive signals, the metanephric
      mesenchyme aggregates, becomes polarized, and generates much of the epithelia of
      the nephron. As such, the metanephric mesenchyme is a renal progenitor cell
      population that must be replenished as epithelial derivatives are continuously
      generated. The molecular mechanisms that maintain the undifferentiated state of
      the metanephric mesenchymal precursor cells have not yet been identified. In this
      paper, we report that functional inactivation of the homeobox gene Six2 results
      in premature and ectopic differentiation of mesenchymal cells into epithelia and
      depletion of the progenitor cell population within the metanephric mesenchyme.
      Failure to renew the mesenchymal cells results in severe renal hypoplasia. Gain
      of Six2 function in cortical metanephric mesenchymal cells was sufficient to
      prevent their epithelial differentiation in an organ culture assay. We propose
      that in the developing kidney, Six2 activity is required for maintaining the
      mesenchymal progenitor population in an undifferentiated state by opposing the
      inductive signals emanating from the ureteric bud.

PMID- 17036047
TI  - Cap-free structure of eIF4E suggests a basis for conformational regulation by its
      ligands.
AB  - The activity of the eukaryotic translation initiation factor eIF4E is modulated
      through conformational response to its ligands. For example, eIF4G and eIF4E
      binding proteins (4E-BPs) modulate cap affinity, and thus physiological activity
      of eIF4E, by binding a site distal to the 7-methylguanosine cap-binding site.
      Further, cap binding substantially modulates eIF4E's affinity for eIF4G and the
      4E-BPs. To date, only cap-bound eIF4E structures were reported. In the absence of
      structural information on the apo form, the molecular underpinnings of this
      conformational response mechanism cannot be established. We report here the first
      cap-free eIF4E structure. Apo-eIF4E exhibits structural differences in the cap
      binding site and dorsal surface relative to cap-eIF4E. Analysis of structure and
      dynamics of apo-eIF4E, and changes observed upon ligand binding, reveal a
      molecular basis for eIF4E's conformational response to these ligands. In
      particular, alterations in the S4-H4 loop, distal to either the cap or eIF4G
      binding sites, appear key to modulating these effects. Mutation in this loop
      mimics these effects. Overall, our studies have important implications for the
      regulation of eIF4E.

PMID- 17036048
TI  - Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP
      gated P2X7 receptor.
AB  - P2X(7) receptors are ATP-gated cation channels; their activation in macrophage
      also leads to rapid opening of a membrane pore permeable to dyes such as
      ethidium, and to release of the pro-inflammatory cytokine, interleukin-1beta (IL
      1beta). It has not been known what this dye-uptake path is, or whether it is
      involved in downstream signalling to IL-1beta release. Here, we identify pannexin
      1, a recently described mammalian protein that functions as a hemichannel when
      ectopically expressed, as this dye-uptake pathway and show that signalling
      through pannexin-1 is required for processing of caspase-1 and release of mature
      IL-1beta induced by P2X(7) receptor activation.

PMID- 17036049
TI  - Myelin basic protein-dependent plasma membrane reorganization in the formation of
      myelin.
AB  - During vertebrate development, oligodendrocytes wrap their plasma membrane around
      axons to produce myelin, a specialized membrane highly enriched in
      galactosylceramide (GalC) and cholesterol. Here, we studied the formation of
      myelin membrane sheets in a neuron-glia co-culture system. We applied different
      microscopy techniques to visualize lipid packing and dynamics in the
      oligodendroglial plasma membrane. We used the fluorescent dye Laurdan to examine
      the lipid order with two-photon microscopy and observed that neurons induce a
      dramatic lipid condensation of the oligodendroglial membrane. On a nanoscale
      resolution, using stimulated emission depletion and fluorescence resonance energy
      transfer microscopy, we demonstrated a neuronal-dependent clustering of GalC in
      oligodendrocytes. Most importantly these changes in lipid organization of the
      oligodendroglial plasma membrane were not observed in shiverer mice that do not
      express the myelin basic protein. Our data demonstrate that neurons induce the
      condensation of the myelin-forming bilayer in oligodendrocytes and that MBP is
      involved in this process of plasma membrane rearrangement. We propose that this
      mechanism is essential for myelin to perform its insulating function during nerve
      conduction.

PMID- 17036050
TI  - New p63 targets in keratinocytes identified by a genome-wide approach.
AB  - p63 is a developmentally regulated transcription factor related to p53. It is
      involved in the development of ectodermal tissues, including limb, skin and in
      general, multilayered epithelia. The DeltaNp63alpha isoform is thought to play a
      'master' role in the asymmetric division of epithelial cells. It is also involved
      in the pathogenesis of several human diseases, phenotypically characterized by
      ectodermal dysplasia. Our understanding of transcriptional networks controlled by
      p63 is limited, owing to the low number of bona fide targets. To screen for new
      targets, we employed chromatin immunoprecipitation from keratinocytes (KCs)
      coupled to the microarray technology, using both CpG islands and promoter arrays.
      The former revealed 96 loci, the latter yielded 85 additional genes. We tested 40
      of these targets in several functional assays, including: (i) in vivo binding by
      p63 in primary KCs; (ii) expression analysis in differentiating HaCaT cells and
      in cells overexpressing DeltaNp63alpha; (iii) promoter transactivation and (iv)
      immunostaining in normal tissues, confirming their regulation by p63. We
      discovered several new specific targets whose functional categorization links p63
      to cell growth and differentiation.

PMID- 17036051
TI  - In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain
      heterodimer.
AB  - The human ATP-binding cassette (ABC) protein CFTR (cystic fibrosis transmembrane
      conductance regulator) is a chloride channel, whose dysfunction causes cystic
      fibrosis. To gain structural insight into the dynamic interaction between CFTR's
      nucleotide-binding domains (NBDs) proposed to underlie channel gating, we
      introduced target cysteines into the NBDs, expressed the channels in Xenopus
      oocytes, and used in vivo sulfhydryl-specific crosslinking to directly examine
      the cysteines' proximity. We tested five cysteine pairs, each comprising one
      introduced cysteine in the NH(2)-terminal NBD1 and another in the COOH-terminal
      NBD2. Identification of crosslinked product was facilitated by co-expression of
      NH(2)-terminal and COOH-terminal CFTR half channels each containing one NBD. The
      COOH-terminal half channel lacked all native cysteines. None of CFTR's 18 native
      cysteines was found essential for wild type-like, phosphorylation- and ATP
      dependent, channel gating. The observed crosslinks demonstrate that NBD1 and NBD2
      interact in a head-to-tail configuration analogous to that in homodimeric crystal
      structures of nucleotide-bound prokaryotic NBDs. CFTR phosphorylation by PKA
      strongly promoted both crosslinking and opening of the split channels, firmly
      linking head-to-tail NBD1-NBD2 association to channel opening.

PMID- 17036052
TI  - A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death.
AB  - The intermediate filament protein, nestin, has been implicated as an organizer of
      survival-determining signaling molecules. When nestin expression was related to
      the sensitivity of neural progenitor cells to oxidant-induced apoptosis, nestin
      displayed a distinct cytoprotective effect. Oxidative stress in neuronal
      precursor cells led to downregulation of nestin with subsequent activation of
      cyclin-dependent kinase 5 (Cdk5), a crucial kinase in the nervous system. Nestin
      downregulation was a prerequisite for the Cdk5-dependent apoptosis, as
      overexpression of nestin efficiently inhibited induction of apoptosis, whereas
      depletion of nestin by RNA interference had a sensitizing effect. When the
      underlying link between nestin and Cdk5 was analyzed, we observed that nestin
      serves as a scaffold for Cdk5, with binding restricted to a specific region
      following the alpha-helical domain of nestin, and that the presence and
      organization of nestin regulated the sequestration and activity of Cdk5, as well
      as the ubiquitylation and turnover of its regulator, p35. Our data imply that
      nestin is a survival determinant whose action is based upon a novel mode of Cdk5
      regulation, affecting the targeting, activity, and turnover of the Cdk5/p35
      signaling complex.

PMID- 17036053
TI  - Epigenetic determination of a cell-specific gene expression program by ATF-2 and
      the histone variant macroH2A.
AB  - Transcriptional activation of the interleukin-8 (IL-8) gene is restricted to
      distinct cell types, although the transcriptional regulatory proteins controlling
      IL-8 gene expression are ubiquitous. We show that cell-specific transcription of
      IL-8 is due to the distinct chromatin architecture on the enhancer/promoter
      before the arrival of the inducing signal. In expressing epithelial cells the
      enhancer/promoter is nucleosome-free, whereas in non-expressing B cells a
      nucleosome masks the entire regulatory region. The B-cell-specific nucleosome
      contains the histone variant macroH2A, which is responsible for preventing
      transcription factor binding. Recruitment of the repressive macroH2A nucleosome
      requires direct interactions between ATF-2 bound to the nearby AP1 site and
      macroH2A and it is regulated by DNA-induced protein allostery. siRNA against ATF
      2 or macroH2A rescues IL-8 transcription in B cells. Thus, a transcription factor
      can work as a transcriptional repressor by orchestrating and maintaining the
      assembly of specialized local chromatin architectures.

PMID- 17036054
TI  - Microtubule depolymerization can drive poleward chromosome motion in fission
      yeast.
AB  - Prometaphase kinetochores interact with spindle microtubules (MTs) to establish
      chromosome bi-orientation. Before becoming bi-oriented, chromosomes frequently
      exhibit poleward movements (P-movements), which are commonly attributed to minus
      end-directed, MT-dependent motors. In fission yeast there are three such motors:
      dynein and two kinesin-14s, Pkl1p and Klp2p. None of these enzymes is essential
      for viability, and even the triple deletion grows well. This might be due to the
      fact that yeasts kinetochores are normally juxtapolar at mitosis onset, removing
      the need for poleward chromosome movement during prometaphase. Anaphase P
      movement might also be dispensable in a spindle that elongates significantly. To
      test this supposition, we have analyzed kinetochore dynamics in cells whose
      kinetochore-pole connections have been dispersed. In cells recovering from this
      condition, the maximum rate of poleward kinetochore movement was unaffected by
      the deletion of any or all of these motors, strongly suggesting that other
      factors, like MT depolymerization, can cause such movements in vivo. However,
      Klp2p, which localizes to kinetochores, contributed to the effectiveness of P
      movement by promoting the shortening of kinetochore fibers.

PMID- 17036055
TI  - The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand
      DNA crosslinks into double-strands breaks.
AB  - Repair of interstrand crosslinks (ICLs) requires multiple-strand incisions to
      separate the two covalently attached strands of DNA. It is unclear how these
      incisions are generated. DNA double-strand breaks (DSBs) have been identified as
      intermediates in ICL repair, but enzymes responsible for producing these
      intermediates are unknown. Here we show that Mus81, a component of the Mus81-Eme1
      structure-specific endonuclease, is involved in generating the ICL-induced DSBs
      in mouse embryonic stem (ES) cells in S phase. Given the DNA junction cleavage
      specificity of Mus81-Eme1 in vitro, DNA damage-stalled replication forks are
      suitable in vivo substrates. Interestingly, generation of DSBs from replication
      forks stalled due to DNA damage that affects only one of the two DNA strands did
      not require Mus81. Furthermore, in addition to a physical interaction between
      Mus81 and the homologous recombination protein Rad54, we show that Mus81(-/-)
      Rad54(-/-) ES cells were as hypersensitive to ICL agents as Mus81(-/-) cells. We
      propose that Mus81-Eme1- and Rad54-mediated homologous recombination are involved
      in the same DNA replication-dependent ICL repair pathway.

PMID- 17036056
TI  - Decreased immune reactivity towards a knobless, affibody-targeted adenovirus type
      5 vector.
AB  - In this study, a prototype Adenovirus type 5 (Ad5) vector deleted of the fiber
      knob domain and carrying an Affibody molecule as the targeting ligand showed
      decreased susceptibility to human pre-existing antibodies. This vector, Ad5/R7
      Z(taq)Z(taq), has short fibers carrying seven shaft repeats, a non-native
      trimerization signal and an affibody molecule (Z(taq)) reactive to Taq
      polymerase. Ad5/R7-Z(taq)Z(taq) could be specifically targeted to 293 cells
      stably expressing membrane-bound anti-Z(taq) idiotypic affibody called Z(ztaq)
      (293Z(ztaq)). Sera from 50 blood donors were analyzed for neutralization activity
      (NA) against the parental Ad5/Fiwt vector and knobless Ad5/R7-Z(taq)Z(taq) on
      293Z(ztaq) cells. Twenty-three sera had NA titers (> or =1:64) against Ad5/Fiwt
      (46%) and only two against Ad5/R7-Z(taq)Z(taq) (4%). Characterization of sera
      with NA titers showed that the knob domain is one of the targets of the
      antibodies. Neutralization assays using sera pre-adsorbed on knob and hexon
      proteins showed that the NA of the sera was carried mainly by anti-knob and anti
      hexon antibodies, but in certain sera the anti-hexon antibodies represent the
      major population of the neutralizing antibodies (NAbs). Our results suggested
      that a combination of knob deletion and hexon switching could be an effective
      strategy for Ad vectors to better evade the anti-Ad NAbs.

PMID- 17036057
TI  - Dendritic cells transfected with interleukin-12 and tumor-associated antigen
      messenger RNA induce high avidity cytotoxic T cells.
AB  - Dendritic cells (DC) transfected with messenger RNA (mRNA) encoding tumor
      associated antigens (TAA) are able to induce potent tumor-specific T-cell
      responses directed to a broad spectrum of tumor-associated epitopes. The in vitro
      generation of DC possessing all the features crucial for the induction of type 1
      immune responses, such as mature state, migratory potential and interleukin-12
      (IL-12p70) production is complicated. Particularly migratory potential is
      inversely correlated with IL-12p70 production after maturation with prostaglandin
      E2 (PGE2), which is included in maturation cocktails currently used in most
      vaccination trials. Here, we show that transfection of PGE2 matured DC with a
      single mRNA strain encoding for ubiquitin followed by a TAA which was linked to
      IL-12 by a self-cleaving 2A sequence, produced biological active IL-12p70 and
      were able to present the transfected TAA up to 72 h after transfection.
      Furthermore, use of the anti-reverse cap analog for in vitro transcription of the
      IL-12 mRNA enabled constitutive IL-12p70 production for up to 5 days. These
      transfected mature DC migrated efficiently towards lymph node derived chemokines.
      DCs constitutively expressing IL-12p70, generate TAA-specific cytotoxic T cells
      with an high functional avidity, independent of CD4+ T-cell help.

PMID- 17036058
TI  - Pig liver gene therapy by noninvasive interventionist catheterism.
AB  - The efficacy of noninvasive interventionist catheterism in large animals as an
      alternative to the hydrodynamic procedure, described for small animals, is
      evaluated. Basically, gene transfer is performed by implantation and fixation of
      a balloon catheter within the suprahepatic vein of anesthetized pigs, through the
      femoral vein. The catheter tip is identified by fluoroscopy, injecting a contrast
      solution that marks large or small hepatic territories. Animals were injected
      with a 100 ml pTG7101 plasmid solution (40 microg/ml), which contains the human
      alpha-1 antitrypsin gene, perfused at a rate of 7.5 ml/s and efficacy and
      toxicity of the procedure were evaluated. The results show: (i) the highest
      efficacy in protein production is reached when perfusion is limited to small
      areas of the liver; (ii) no relevant hepatic toxicity was observed; (iii) gene
      transfer is mainly located in the areas around the central vein, as seen in the
      immunohistochemical studies; (iv) the electron microscopy studies indicate that
      the areas with good transfection efficacy show the presence of abundant endocytic
      vesicles that may even fuse among themselves. These data suggest that retrovenous
      injection by noninvasive interventionist catheterism could become an efficient
      procedure for hepatic gene transfer with potential clinical applications.

PMID- 17036059
TI  - The ripples of "The Big (agricultural) Bang": the spread of early wheat
      cultivation.
AB  - Demographic expansion and (or) migrations leave their mark in the pattern of DNA
      polymorphisms of the respective populations. Likewise, the spread of cultural
      phenomena can be traced by dating archaeological finds and reconstructing their
      direction and pace. A similar course of events is likely to have taken place
      following the "Big Bang" of the agricultural spread in the Neolithic Near East
      from its core area in southeastern Turkey. Thus far, no attempts have been made
      to track the movement of the founder genetic stocks of the first crop plants from
      their core area based on the genetic structure of living plants. In this
      minireview, we re-interpret recent wheat DNA polymorphism data to detect the
      genetic ripples left by the early wave of advance of Neolithic wheat farming from
      its core area. This methodology may help to suggest a model charting the spread
      of the first farming phase prior to the emergence of truly domesticated wheat
      types (and other such crops), thereby increasing our resolution power in studying
      this revolutionary period of human cultural, demographic, and social evolution.

PMID- 17036060
TI  - Haplotype characterization and markers at the barley Mlo powdery mildew
      resistance locus as tools for marker-assisted selection.
AB  - Recessive mlo alleles of the barley Mlo gene confer resistance to almost all
      known isolates of the powdery mildew fungal pathogen targeting barley (Hordeum
      vulgare). To characterize haplotypes present in the Mlo chromosomal region of
      cultivated Mlo and mlo barley genotypes, we conducted a polymorphism search in 3
      predicted low-copy sequence regions adjacent to the Mlo gene by examining a
      sample of 4 Mlo and 3 mlo cultivars. Eight single-nucleotide polymorphisms (SNPs)
      and 1 insertion-deletion (indel) were detected, and easy to use PCR-based markers
      were developed for typing the SNPs. The PCR markers were used to characterize a
      collection of 46 Mlo and 25 mlo barley cultivars, identifying 3 distinct mlo-11
      haplotypes, 1 mlo-9 haplotype, and 4 Mlo haplotypes. We summarized the haplotype
      and marker information obtained here and in a previous study to help breeders
      identify strategies for mlo marker-assisted selection. The ability of the markers
      to identify mlo-resistant genotypes in segregating populations was demonstrated
      using 2 resistance-characterized F2 populations derived by 3-way crosses.

PMID- 17036061
TI  - Genetic analysis and molecular mapping of the avirulence gene PRE1, a gene for
      host-species specificity in the blast fungus Magnaporthe grisea.
AB  - We analyzed host-species specificity of Magnaporthe grisea on rice using 110 F1
      progeny derived from a cross between the Oryza isolate CH87 (pathogenic to rice)
      and the Digitaria isolate 6023 (pathogenic to crabgrass). To elucidate the
      genetic mechanisms controlling species specificity in M. grisea, we performed a
      genetic analysis of species-specific avirulence on this rice population.
      Avirulent and virulent progeny segregated in a 1:1 ratio on the 2 rice cultivars
      'Lijiangxintuanheigu' (LTH) and 'Shin2', suggesting that a single locus,
      designated PRE1, was involved in the specificity. In a combination between
      'Kusabue' and 'Tsuyuake', the segregation of the 4 possible phenotypes of F1
      progeny was significantly different from the expected 3:1:3:1 and instead fit a
      ratio of 2:0:1:1. This indicated that 2 loci, PRE1 and AVR2, were involved in
      specific parasitism on rice. These results suggest that the species specificity
      of M. grisea on rice is governed by species-dependent genetic mechanisms that are
      similar to the gene-for-gene interactions controlling cultivar specificity.
      Pathogenicity tests with various plant species revealed that the Digitaria
      isolate 6023 was exclusively parasitic on crabgrass. Genetic linkage analysis
      showed that PRE1 was mapped on chromosome 3 with respect to RAPD and SSR markers.
      RAPD marker S361 was linked to the avirulence gene at a distance of ~6.4 cM. Two
      SSR markers, m677-678 and m77-78, were linked to the PRE1 gene on M. grisea
      chromosome 3 at distances of 5.9 and 7.1 cM, respectively. Our results will
      facilitate positional cloning and functional studies of this gene.

PMID- 17036063
TI  - Molecular characterization of ribosomal intergenic spacer in the tadpole shrimp
      Triops cancriformis (Crustacea, Branchiopoda, Notostraca).
AB  - Nuclear ribosomal DNA constitutes a multigene family, with tandemly arranged
      units linked by an intergenic spacer (IGS), which contains initiation/termination
      transcription signals and usually tandemly arranged subrepeats. The structure and
      variability of the IGS region are analyzed here in hermaphroditic and
      parthenogenetic populations of the "living fossil" Triops cancriformis
      (Branchiopoda, Notostraca). The results indicate the presence of concerted
      evolution at the population level for this G+C-rich IGS region as a whole, with
      the major amount of genetic variability found outside the subrepeat region. The
      subrepeats region is composed of 3 complete repeats (a, c, d) intermingled with 3
      repeat fragments (b, e, f) and unrelated sequences. The most striking datum is
      the absolute identity of subrepeats (except type d) occupying the same position
      in different individuals/populations. A putative promoter sequence is present
      upstream of the 18S rRNA gene, but not in subrepeats, which is at variance with
      other arthropod IGSs. The absence of a promoter sequence in the subrepeats and
      subrepeat sequence conservation suggests that this region acts as an enhancer
      simply by its repetitive nature, as observed in some vertebrates. The putative
      external transcribed spacer (840 bp) shows hairpin structures, as in yeasts,
      protozoans, Drosophila, and vertebrates.

PMID- 17036064
TI  - Determination of mRNA half-lives in Candida albicans using thiolutin as a
      transcription inhibitor.
AB  - A method for determining mRNA half-lives in the polymorphic fungus Candida
      albicans is described. It employs growth in a defined medium, the inhibition of
      transcription with thiolutin (10-20 microg/mL), and quantitative Northern
      blotting. The method is effective for the A72, SC5314, and CAI-4 strains of C.
      albicans, and for mRNAs that have a wide variety of decay rates and steady-state
      abundances. The range of half-lives detected (from 4-168 min) shows that this
      method is effective for mRNAs with widely varying half-lives. The mRNA decay
      rates obtained are compared with those for orthologous mRNAs from Saccharomyces
      cerevisiae. This procedure should work for a broad range of C. albicans strains
      and can be adapted to other fungal species.

PMID- 17036065
TI  - Distributional gradient of amino acid repeats in plant proteins.
AB  - A computer-based analysis was conducted to assess the characteristics of amino
      acid repeats in Arabidopsis and rice. Our analysis showed a negative gradient in
      amino acid repeat distribution along the direction of translation in plants.
      Repeat occurrences are obviously associated with position in plant proteins but
      are not consistent with the corresponding amino acid contents. These repeats are
      encoded by the mixed synonymous codons rather than the uninterrupted reiterations
      of a single codon, and both Arabidopsis and rice have gradients in their
      distribution. Functional investigation showed that these repeat-containing
      proteins are preferentially involved in transcription regulation and protein
      ubiquitination but significantly underrepresented in the processes of DNA
      recombination and DNA replication. These data reveal that the direction-related
      mutation bias and functional selection have influenced the distribution of amino
      acid repeats in plants.

PMID- 17036066
TI  - Genetic diversity among varieties of the native forage grass Trichloris crinita
      based on AFLP markers, morphological characters, and quantitative agronomic
      traits.
AB  - We assessed the genetic diversity in Trichloris crinita (Poaceae) varieties from
      South America, using AFLPs, morphological characters, and quantitative agronomic
      traits. Owing to the importance of this species for range grazing, we first
      characterized the varieties based on forage productivity. Biomass production
      varied 9 fold among the materials evaluated. Analysis of AFLP fingerprints
      allowed the discrimination of all varieties with a few selected primer
      combinations. Pair-wise genetic similarities, using marker data, ranged from 0.31
      to 0.92 (Jaccard coefficients). Marker-based unweighted pair group method with
      arithmetic averaging (UPGMA) cluster analysis did not show geographical
      clustering, but rather grouped the varieties according to their biomass
      production. We identified 18 markers associated with biomass production, of which
      8 showed complete correlation (r = 1.00) with this trait. These DNA markers can
      be used to assist selection for high forage productivity in T. crinita. Cluster
      analysis using morphological and quantitative characters revealed 4 distinct
      groups of varieties, clearly separated according to their biomass yield. The
      variables foliage height and basal diameter were strongly correlated with biomass
      production and these phenotypic markers can be used to select productive plants.
      The relations among the varieties based on AFLP data were significantly
      correlated with those based on agronomic and morphological characters, suggesting
      that the 2 systems give similar estimates of genetic relations among the
      varieties.

PMID- 17036067
TI  - Assessment of genetic diversity in cultivars of white clover (Trifolium repens
      L.) detected by SSR polymorphisms.
AB  - White clover (Trifolium repens L.) is an important temperate pasture legume that
      plays a key role as a companion to grass species, such as perennial ryegrass
      (Lolium perenne L.). Due to the outbreeding nature of white clover, cultivars are
      highly heterogeneous. Genetic diversity was assessed using 16 elite cultivars
      from Europe, North and South America, Australia, and New Zealand. Fifteen simple
      sequence repeat markers that detect single, codominant polymorphic genetic loci
      were selected for the study. The genetic relationships among individuals were
      compared using phenetic clustering, and those among cultivars were compared using
      nonmetric multidimensional scaling. Intrapopula tion variability exceeded
      interpopulation variability, with substantial overlap among populations and weak
      interpopula tion differentiation. No obvious or significant differentiation was
      observed on the basis of morphology or geographic origin of the cultivars. The
      number of parental genotypes used to derive each cultivar was not a major
      determinant of genome-wide genetic diversity. The outcomes of this assessment of
      genetic variation in elite white clover germplasm pools have important
      implications for the feasibility of molecular marker-based cultivar
      discrimination, and will be used to assist the design of linkage disequilibrium
      mapping strategies for marker-trait association.

PMID- 17036068
TI  - Structural organization of the mitochondrial DNA control region in Aedes aegypti.
AB  - The complete A+T - rich region of Aedes aegypti mitochondrial DNA has been cloned
      and sequenced. In Argentinean populations of the species, a polymorphism in the
      length of the amplified fragment was observed. Nucleotide sequence comparison of
      the shortest and longest A+T - rich amplified fragments detected revealed the
      presence of 2 types of tandemly repeated blocks. The size variation observed in
      natural populations is mainly due to the presence of a variable number of a 181
      bp tandem repeat unit, located toward the 12S rRNA gene end. The size of the
      longest A+T - rich region was of 2070 bp, representing the largest control
      sequence reported for any mosquito species. Few relevant short blocks of primary
      sequence similarity conserved in the control region of mosquitoes and other
      insects were detected scattered throughout the whole region. Five putative stem
      loop secondary structures were found, one of them flanked by conserved sequences
      described in other insects. Our results suggest that there are no universal
      models of structure-function relations in the control region of insect mtDNA. In
      addition, we identified a short A+T - rich variable segment in the Ae. aegyti
      control region that would be suitable for population genetic studies.

PMID- 17036069
TI  - Molecular marker diversity of SCN-resistant sources in soybean.
AB  - Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe; HG) is one of the most
      destructive pests of soybean (Glycine max (L.) Merr.) in the United States. Over
      100 SCN-resistant accessions within the USDA Soybean Germplasm Collection have
      been identified, but little is known about the genetic diversity of this SCN
      resistant germplasm. The objective of this research was to evaluate the genetic
      variation and determine the genetic relationships among SCN-resistant accessions.
      One hundred twenty-two genotypes were evaluated by 85 simple sequence repeat
      (SSR) markers from 20 linkage groups. Non-hierarchical (VARCLUS) and hierarchical
      (Ward's) clustering were combined with multidimensional scaling (MDS) to
      determine relationships among tested lines. The 85 SSR markers produced 566
      allelic fragments with a mean polymorphic information content (PIC) value of
      0.35. The 122 lines were grouped into 7 clusters by 2 different clustering
      methods and the MDS results consistently corresponded to the assigned clusters.
      Assigned clusters were dominated by genotypes that possess one or more unique SCN
      resistance genes and were associated with geographical origins. The results of
      analysis of molecular variance (AMOVA) showed that the variation differences
      among clusters and individual lines were significant, but the differences among
      individuals within clusters were not significant.

PMID- 17036070
TI  - Timing and rate of genome variation in triticale following allopolyploidization.
AB  - The timing and rate of genomic variation induced by allopolyploidization in the
      intergeneric wheat-rye (Triticum spp. - Secale cereale L.) hybrid triticale (x
      Triticosecale Wittmack) was studied using amplified fragment length polymorphism
      (AFLP) analyses with 2 sets of primers, EcoRI-MseI (E-M) and PstI-MseI (P-M),
      which primarily amplify repetitive and low-copy sequences, respectively. The
      results showed that allopolyploidization induced genome sequence variation in
      triticale and that a great degree of the genome variation occurred immediately
      following wide hybridization. Specifically, about 46.3% and 36.2% of the wheat
      parental band loss and 74.5% and 68.4% of the rye parental band loss occurred in
      the F1 hybrids (before chromosome doubling) for E-M and P-M primers,
      respectively. The sequence variation events that followed chromosome doubling
      consisted of continuous modifications that occurred at a very small rate compared
      with the rate of variation before chromosome doubling. However, the rate of
      sequence variation involving the rye parental genome was much higher in the first
      5 generations following chromosome doubling than in any subsequent generation.
      Surprisingly, the highest rate of rye genomic variation occurring after
      chromosome doubling was in C3 or later, but not in C1. The data suggested that
      the cytoplasm and the degree of the relationship between the parental genomes
      were the key factors in determining the direction, amount, timing, and rate of
      genomic sequence variation occurring during intergeneric allopolyploidization.

PMID- 17036062
TI  - Analysis of expressed sequence tags from a naked foraminiferan Reticulomyxa
      filosa.
AB  - Foraminifers are a major component of modern marine ecosystems and one of the
      most important oceanic producers of calcium carbonate. They are a key
      phylogenetic group among amoeboid protists, but our knowledge of their genome is
      still mostly limited to a few conserved genes. Here, we report the first study of
      expressed genes by means of expressed sequence tag (EST) from the freshwater
      naked foraminiferan Reticulomyxa filosa. Cluster analysis of 1630 valid ESTs
      enabled the identification of 178 groups of related sequences and 871 singlets.
      Approximately 50% of the putative unique 1059 ESTs could be annotated using Blast
      searches against the protein database SwissProt + TrEMBL. The EST database
      described here is the first step towards gene discovery in Foraminifera and
      should provide the basis for new insights into the genomic and transcriptomic
      characteristics of these interesting but poorly understood protists.

PMID- 17036071
TI  - Development and linkage mapping of E-STS and RGA markers for functional gene
      homologues in apple.
AB  - Linkage maps developed from known-function genes can be valuable in the candidate
      gene mapping approach. A set of 121 expressed sequence tagged site (E-STS) primer
      pairs were tested on a framework genetic linkage map of apple (Malus x domestica
      Borkh.) constructed using simple sequence repeats (SSRs) and randomly amplified
      polymorphic DNA (RAPD) markers. These known-function gene markers, E-STSs, were
      supplemented by markers for resistance gene analogues (RGAs), designed based on
      conserved motifs in all characterized resistance genes isolated from plant
      species. A total of 229 markers, including 46 apple E-STSs, 8 RGAs, 85 SSRs from
      apple and peach, and 88 RAPDs, were assigned to 17 linkage groups covering 832 cM
      of the apple genome, based on 52 individuals originating from the cross
      'Antonovka debnicka' (Q12-4) x 'Summerred'. Clusters of E-STS and RGA loci were
      located in linkage groups previously identified to carry resistance genes, some
      of which confer resistance to apple scab disease caused by Venturia inaequalis
      (Cke.) Wint.

PMID- 17036072
TI  - Isolation, characterization, and linkage analyses of 74 novel microsatellites in
      Barramundi (Lates calcarifer).
AB  - Barramundi (Lates calcarifer) is an important marine food fish species in
      Southeast Asia and Australia. Seventy-four novel microsatellites were isolated
      from a genomic DNA library enriched for CA repeats and were characterized in 24
      unrelated individuals. Among the 74 microsatellites, 71 were polymorphic, with an
      average allele number of 7.0 +/- 3.6/locus. The average expected heterozygosity
      of these polymorphic markers was 0.66. Sixty-three of the 71 polymorphic
      microsatellites conformed to Hardy-Weinberg equilibrium. Linkage analyses were
      conducted in a reference family, leading to the assignment of 34 novel
      microsatellites and 16 published markers in 16 linkage groups. The novel
      microsatellites developed in this study will contribute significantly to the
      construction of a first-generation linkage map for mapping of quantitative trait
      loci in Barramundi, and supply a large choice of markers for studies on
      population genetics, stock management, and pedigree reconstruction.

PMID- 17036073
TI  - Characterization of genetic loci conferring adult plant resistance to leaf rust
      and stripe rust in spring wheat.
AB  - Leaf (brown) and stripe (yellow) rusts, caused by Puccinia triticina and Puccinia
      striiformis, respectively, are fungal diseases of wheat (Triticum aestivum) that
      cause significant yield losses annually in many wheat-growing regions of the
      world. The objectives of our study were to characterize genetic loci associated
      with resistance to leaf and stripe rusts using molecular markers in a population
      derived from a cross between the rust-susceptible cultivar 'Avocet S' and the
      resistant cultivar 'Pavon76'. Using bulked segregant analysis and partial linkage
      mapping with AFLPs, SSRs and RFLPs, we identified 6 independent loci that
      contributed to slow rusting or adult plant resistance (APR) to the 2 rust
      diseases. Using marker information available from existing linkage maps, we have
      identified additional markers associated with resistance to these 2 diseases and
      established several linkage groups in the 'Avocet S' x 'Pavon76' population. The
      putative loci identified on chromosomes 1BL, 4BL, and 6AL influenced resistance
      to both stripe and leaf rust. The loci on chromosomes 3BS and 6BL had significant
      effects only on stripe rust, whereas another locus, characterized by AFLP
      markers, had minor effects on leaf rust only. Data derived from Interval mapping
      indicated that the loci identified explained 53% of the total phenotypic
      variation (R2) for stripe rust and 57% for leaf rust averaged across 3 sets of
      field data. A single chromosome recombinant line population segregating for
      chromosome 1B was used to map Lr46/Yr29 as a single Mendelian locus.
      Characterization of slow-rusting genes for leaf and stripe rust in improved wheat
      germplasm would enable wheat breeders to combine these additional loci with known
      slow-rusting loci to generate wheat cultivars with higher levels of slow-rusting
      resistance.

PMID- 17036074
TI  - Developmental characterization of the fasciated locus and mapping of Arabidopsis
      candidate genes involved in the control of floral meristem size and carpel number
      in tomato.
AB  - Mutation at the fasciated locus was a key step in the production of extreme fruit
      size during tomato domestication. To shed light on the nature of these changes,
      near-isogenic lines were used for a comparative developmental study of fasciated
      and wild-type tomato plants. The fasciated gene directly affects floral meristem
      size and is expressed before the earliest stages of flower organogenesis. As a
      result, mature fruit of fasciated mutants have more carpels (locules) and greater
      fruit diameter and mass. The discovery that fasciated affects floral meristem
      size led to a search for candidate genes from Arabidopsis known to be involved in
      floral meristem development. Putative homologs were identified in a large tomato
      EST database, verified through phylogenetic analyses, and mapped in tomato; none
      mapped to the fasciated locus; however, putative homologs of WUS and WIG mapped
      to the locule number locus on chromosome 2, the second major transition to large
      tomato fruit, with WUS showing the highest association. In other cases, minor
      QTLs for floral organ number (lcn2.2) and (stn11.2) co-localized with a CLV1
      paralog and with the syntenic region containing the CLV3 gene in Arabidopsis,
      respectively.

PMID- 17036075
TI  - The genome of Oscheius tipulae: determination of size, complexity, and structure
      by DNA reassociation using fluorescent dye.
AB  - This work describes the physicochemical characterization of the genome and
      telomere structure from the nematode Oscheius tipulae CEW1. Oscheius tipulae is a
      free-living nematode belonging to the family Rhabditidae and has been used as a
      model system for comparative genetic studies. A new protocol that combines
      fluorescent detection of double-stranded DNA and S1 nuclease was used to
      determine the genome size of O. tipulae as 100.8 Mb (approximately 0.1 pg
      DNA/haploid nucleus). The genome of this nematode is made up of 83.4% unique copy
      sequences, 9.4% intermediate repetitive sequences, and 7.2% highly repetitive
      sequences, suggesting that its structure is similar to those of other nematodes
      of the genus Caenorhabditis. We also showed that O. tipulae has the same telomere
      repeats already found in Caenorhabditis elegans at the ends and in internal
      regions of the chromosomes. Using a cassette-ligation-mediated PCR protocol we
      were able to obtain 5 different putative subtelomeric sequences of O. tipulae,
      which show no similarity to C. elegans or C. briggsae subtelomeric regions. DAPI
      staining of hermaphrodite gonad cells show that, as detected in C. elegans and
      other rhabditids, O. tipulae have a haploid complement of 6 chromosomes.

PMID- 17036076
TI  - Fine mapping of a pistilloid-stamen (PS) gene on the short arm of chromosome 1 in
      rice.
AB  - A novel floral organ mutant of rice (Oryza sativa L. subsp. indica), termed
      pistilloid-stamen (ps) here, has flowers with degenerated lemma and palea, with
      some stamens transformed into pistils and pistil-stamen chimeras. Genetic
      analysis confirmed that the ps trait is controlled by a single recessive gene. F2
      and F3 segregation populations derived from PS ps heterozygote crossed with Oryza
      sativa subsp. indica 'Luhui-17' (PS PS) were used for molecular mapping of the
      gene using simple sequence repeat (SSR) markers. With 97 recessive individuals
      from an F2 segregation population, the ps locus was preliminarily mapped 6.2 cM
      distal to marker RM6324 and 3.1 cM proximal to marker RM6340 in the terminal
      region of the short arm of chromosome 1. With a large F3 segregation population,
      the gene was fine-mapped between markers RM6470 and RM1141, at distances of 0.10
      and 0.03 cM to each marker, respectively. The position of the ps gene was finally
      located within a 20 kb physical region containing 3 annotated putative genes. One
      of them, encoding a protein with a single C2H2 zinc-finger domain, may be the
      candidate gene for PS.

PMID- 17036077
TI  - Phylogenetic reconstruction of Aegilops section Sitopsis and the evolution of
      tandem repeats in the diploids and derived wheat polyploids.
AB  - The evolution of 2 tandemly repeated sequences Spelt1 and Spelt52 was studied in
      Triticum species representing 2 evolutionary lineages of wheat and in Aegilops
      sect. Sitopsis, putative donors of their B/G genomes. Using fluorescence in situ
      hybridization we observed considerable polymorphisms in the hybridization
      patterns of Spelt1 and Spelt52 repeats between and within Triticum and Aegilops
      species. Between 2 and 28 subtelomeric sites of Spelt1 probe were detected in Ae.
      speltoidies, depending on accession. From 8 to 12 Spelt1 subtelomeric sites were
      observed in species of Timopheevi group (GAt genome), whereas the number of
      signals in emmer/aestivum accessions was significantly less (from 0 to 6).
      Hybridization patterns of Spelt52 in Ae. speltoides, Ae. longissima, and Ae.
      sharonensis were species specific. Subtelomeric sites of Spelt52 repeat were
      detected only in T. araraticum (T. timopheevii), and their number and chromosomal
      location varied between accessions. Superimposing copy number data onto our
      phylogenetic scheme constructed from RAPD data suggests 2 major independent
      amplifications of Spelt52 and 1 of Spelt1 repeats in Aegilops divergence. It is
      likely that the Spelt1 amplification took place in the ancient Ae. speltoides
      before the divergence of polyploid wheats. The Spelt52 repeat was probably
      amplified in the lineage of Ae. speltoides prior to divergence of the
      allopolyploid T. timopheevii but after the divergence of T. durum. In a separate
      amplification event, Spelt52 copy number expanded in the common ancestor of Ae.
      longissima and Ae. sharonensis.

PMID- 17036078
TI  - Identification of chromosomal fusion sites in Arabidopsis mutants using
      sequential bicolour BAC-FISH.
AB  - Double stranded chromosomal breaks are repaired by homologous recombination or
      nonhomologous end joining (NHEJ). When broken chromosome ends are fused together
      by NHEJ, the resulting dicentric chromosomes can be detected as anaphase bridges
      during the subsequent mitosis. Telomeres in the absence of functional telomerase
      shorten, became unprotected, and are eventually recognized by the cell repair
      system as double stranded breaks. As result, chromosomes of Arabidopsis thaliana
      plants that are deficient in the gene for telomerase reverse transcriptase (TERT)
      are prone to chromosome fusions. We use Arabidopsis tert-/- mutants as a model
      system for analyzing terminal chromosome fusions. Here we report a novel and
      sensitive cytogenetic assay for the identification and characterization of
      chromosome-terminal fusion events by employing fluorescence in situ hybridization
      (FISH) with multiple probes and a repeated hybridization approach. A mixture of
      chromosome-specific subtelomeric probes is applied successively in 3 FISH
      reactions to the slides containing mitotic anaphase figures with anaphase
      bridges. Each figure is registered by a CCD camera after each in situ
      hybridization procedure. By comparing the signals presented on the bridge in
      successive images the assessment of the particular chromosome arms involved in
      fusion is possible. This experimental setup enables unambiguous identification of
      individual chromosome ends employed in fusion events.

PMID- 17036079
TI  - Loss of genomic imprinting in Drosophila clones.
AB  - Genomic imprinting is a process that genetically distinguishes maternal and
      paternal genomes, and can result in parent-of-origin-dependent monoallelic
      expression of a gene that is dependent on the parent of origin. As such, an
      otherwise functional maternally inherited allele may be silenced so that the gene
      is expressed exclusively from the paternal allele, or vice versa. Once thought to
      be restricted to mammals, genomic imprinting has been documented in angiosperm
      plants (J.L. Kermicle. 1970. Genetics, 66: 69-85), zebrafish (C.C. Martin and R.
      McGowan. 1995. Genet. Res. 65: 21-28), insects, and C. elegans (C.J. Bean, C.E.
      Schaner, and W.G. Kelly. 2004. Nat. Genet. 36: 100-105.). In each case, it
      appears to rely on differential chromatin structure. Aberrant imprinting has been
      implicated in various human cancers and has been detected in a number of cloned
      mammals, potentially limiting the usefulness of somatic nuclear transfer. Here we
      show that genomic imprinting associated with a mini-X chromosome is lost in
      Drosophila melanogaster clones.

PMID- 17036080
TI  - Exact word matches in rice pseudomolecules.
AB  - Using pseudomolecules of assembled genomic sequence, we computed the frequencies
      of 6 to 24 bp oligonucleotide (oligo) "words" across the genome of rice (Oryza
      sativa L. subsp. japonica). All oligos of 10 or fewer basepairs were repeated at
      least 12 times in the genome. The percentage of unique (non-repeated) oligos
      ranged from 0.1% for 12 bp oligos to 76.0% for 24 bp oligos. For three 200 kb
      regions, we annotated each nucleotide position with the genome-wide frequency of
      the 18 bp oligo starting at that position. These frequencies formed landscapes
      consisting of high- and low-frequency zones. Low-frequency zones contained
      occasional high-frequency spikes; these may represent footprints of RIM2
      transposon activity. BLASTn searches of high-frequency non-SSR (simple sequence
      repeat) 18 bp oligos returned few sequences from species other than rice. These
      results demonstrate that, in rice, words are not randomly used between different
      regions within the same genome, and indicate that words that are frequently
      repeated within the rice genome tend to be unique to rice.

PMID- 17036081
TI  - S16, a novel S-RNase allele in the diploid species Solanum chacoense.
AB  - Wild potato species have a gametophytic self-incompatibility system controlled by
      a single multiallelic S locus. In the style, the S-RNase gene codes for an allele
      specific ribonuclease that is involved in the rejection of pollen that carries
      the same S haplotype. This gene has 5 conserved regions (C1-C5) and highly
      variable regions outside of these areas that play a role in S-RNase allele
      specificity. In this work, PCR-mediated amplification of genomic DNA from 2
      Solanum chacoense accessions was performed using primers designed on the basis of
      the C1 and C4 conserved regions. By sequencing the PCR products, a new S-RNase
      allele (S16) was identified in 1 plant of the QBCM argentinian accession.
      Comparison of the partial sequence (from C2 to C3) of S16 RNase with those of 11
      S-RNase genes of other Solanaceae species showed the highest and the lowest
      similarity scores within the same plant species (respectively, 71% with the S11
      and S13 RNase and 35% with the S2 RNase). Differences at the nucleotide level
      between S16 and S11 RNase alleles are discussed.

PMID- 17036083
TI  - Year in review: communicable disease surveillance, 2005.

PMID- 17036084
TI  - The investigation of an outbreak of cryptosporidiosis in New South Wales in 2005.

PMID- 17036085
TI  - Managing a cluster of cryptosporidiosis associated with a public swimming pool.

PMID- 17036086
TI  - Genotyping of Mycobacterium tuberculosis in New South Wales: results from 18
      months of a statewide trial.

PMID- 17036087
TI  - Bug Breakfast in the bulletin: chlamydia, gonorrhoea and syphilis.

PMID- 17036088
TI  - Communicable diseases report, New South Wales, for March and April 2006.

PMID- 17036089
TI  - Perspectives that influence action plans for chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Prompt treatment of acute exacerbations (AEs) in chronic obstructive
      pulmonary disease (COPD) improves quality of life and reduces the use of health
      care resources. Although patient self-management through an individualized action
      plan (AP) can help with early initiation of therapy, its use is critically
      dependent on the patient recognizing the features of an exacerbation. OBJECTIVE:
      To describe COPD patients' experiences with AEs, as well as health care
      professionals' (HCPs') attitudes toward the provision of an AP as part of self
      management education. METHODS: Thirty-two patients with moderate to severe COPD
      who recently experienced at least one AE, and 22 HCPs with experience in the
      management of COPD, were interviewed. RESULTS: The most common symptoms and signs
      associated with an AE were difficulty breathing (84%), fatigue (81%), cold
      symptoms (59%), changes in sputum colour (53%) or amount (47%), and cough (44%).
      The main precipitants identified were environmental triggers (47%), infective
      agents (31%), excessive activities (25%), emotional factors (16%) and changes in
      medications (9%). Strategies for dyspnea relief included increasing medications
      (72%), resting (56%), avoiding exposure to environmental triggers (41%) and
      performing breathing exercises (31%). Patients supported the use of an AP and
      recommended that it be individualized for symptoms and triggers, and that it
      should also include strategies for addressing anxiety and depression. HCPs also
      supported the use of an individualized AP and recommended that it be regularly
      revisited, depending on the patient's disease severity. CONCLUSIONS: Patients'
      experiences with AEs do not always conform to a standard medical definition.
      Therefore, an understanding of their experience is of value in the design of an
      individualized AP. HCPs support the use of an AP that emphasizes self-management
      of exacerbations as well as general COPD management.

PMID- 17036090
TI  - Surgical management of acute necrotizing lung infections.
AB  - BACKGROUND: Surgical resection for acute necrotizing lung infections is not
      widely accepted due to unclear indications and high risk. OBJECTIVE: To review
      results of resection in the setting of acute necrotizing lung infections.
      METHODS: A retrospective review of patients who underwent parenchymal resection
      between January 1, 2000, and January 1, 2006, for management of necrotizing
      pneumonia or lung gangrene. RESULTS: Thirty-five patients underwent resection for
      lung necrosis. At the time of consultation, all patients presented with pulmonary
      sepsis, and also had the following: empyema (n = 17), hemoptysis (n = 5), air
      leak (n = 7), septic shock requiring pressors (n = 8) and inability to oxygenate
      adequately (n = 7). Twenty-four patients were ventilated preoperatively. Eleven
      patients had frank lobar gangrene, and the other patients had combinations of
      necrotizing pneumonia and abscesses. In 10 patients, preresection procedures were
      performed, including percutaneous drainage of an abscess (n = 4), thoracoscopic
      decortication (n = 4) and open decortication (n = 2). Procedures included
      pneumonectomy (n = 4), lobectomy (n = 18), segmentectomy (n = 2), wedge resection
      (n = 4) and debridement (n = 7). There were three (8.5%) postoperative deaths-
      two due to multiple organ failure and one due to anoxic brain injury. All
      patients not ventilated preoperatively were weaned from ventilatory support
      within three days. Of those ventilated preoperatively, three died, while four
      remained chronically ventilator dependent. CONCLUSIONS: Surgical resection for
      necrotizing lung infections is a reasonable option in patients with persistent
      sepsis who are failing medical therapy. Ventilated patients have a worse
      prognosis but can still be candidates for resection. Patients who are
      hemodynamically unstable appear to have better outcomes if they can be stabilized
      before resection.

PMID- 17036091
TI  - Rare lung diseases I--Lymphangioleiomyomatosis.
AB  - The present article is the first in a series that will review selected rare lung
      diseases. The objective of this series is to promote a greater understanding and
      awareness of these unusual conditions among respirologists. Each article will
      begin with a case that serves as a focal point for a discussion of the
      pathophysiology and management of the particular condition. The first article is
      on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary
      alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary
      dyskinesia. LAM is a rare, progressive and (without intervention) often fatal
      interstitial lung disease that predominantly affects women of childbearing age.
      LAM is characterized by progressive interstitial infiltration of the lung by
      smooth muscle cells, resulting in diffuse cystic changes of the lung parenchyma.
      The molecular basis of this disorder has been delineated over the past five years
      and LAM is now known to be a consequence of mutations in the tuberous sclerosis
      genes. This knowledge, combined with advances in our understanding of the
      signalling pathways regulated by these genes, has given rise to potential
      molecular therapies that hold great promise for treating this devastating
      disease.

PMID- 17036092
TI  - Recurrent respiratory papillomatosis causing chronic stridor and delayed speech
      in an 18-month-old boy.
AB  - Recurrent respiratory papillomatosis is a relatively uncommon disease that
      presents clinically with symptoms ranging from hoarseness to severe dyspnea.
      Human papilloma virus types 6 and 11 are important in the etiology of papillomas
      and are most probably transmitted from mother to child during birth. Although
      spontaneous remission is frequent, pulmonary spread and/or malignant
      transformation resulting in death has been reported. CO2 laser evaporation of
      papillomas and adjuvant drug therapy using lymphoblastoid interferon-alpha are
      the most common treatments. However, several other treatments have been tried,
      with varying success. In the present report, a case of laryngeal papillomatosis
      presenting with chronic stridor and delayed speech is described.

PMID- 17036093
TI  - An unusual pulmonary condition presenting following trauma.
AB  - An 18-year-old man presented to the emergency department following an assault. He
      complained of left-sided pleuritic chest pain and difficulty breathing. Clinical
      examination revealed reduced air entry and coarse crepitations at the left lung
      base. A chest x-ray showed a large opacity at the left lung base that contained
      multiple cystic areas with air-fluid levels. Due to the history of trauma, a
      provisional diagnosis of a ruptured hemidiaphragm with small bowel herniation was
      made. Further imaging, including ultrasound, spiral computed tomography and
      magnetic resonance angiography, showed an aberrant vessel supplying the opacity
      and drainage into the pulmonary venous system. A diagnosis of a bronchopulmonary
      sequestration (intralobar type) was made. The differential diagnosis of the
      radiographic appearance is also discussed.

PMID- 17036094
TI  - Canadian Thoracic Society guidelines: diagnosis and treatment of sleep disordered
      breathing in adults.

PMID- 17036095
TI  - The perils of omission.

PMID- 17036096
TI  - Canadian guidelines for training in adult perioperative transesophageal
      echocardiography. Recommendations of the Cardiovascular Section of the Canadian
      Anesthesiologists' Society and the Canadian Society of Echocardiography.
AB  - PURPOSE: To establish Canadian guidelines for training in adult perioperative
      transesophageal echocardiography (TEE). METHODS: Guidelines were established by
      the Canadian Perioperative Echocardiography Group with the support of the
      cardiovascular section of the Canadian Anesthesiologists' Society in conjunction
      with the Canadian Society of Echocardiography. Guidelines for training in
      echocardiography by the American Society of Echocardiography, the American
      College of Cardiology and the Society of Cardiovascular Anesthesiologists were
      reviewed, modified and expanded to produce the 2003 Quebec expert consensus for
      training in perioperative echocardiography. The Quebec expert consensus and the
      2005 guidelines for the provision of echocardiography in Canada formed the basis
      of the Canadian training guidelines in adult perioperative TEE. RESULTS: Basic,
      advanced and director levels of expertise were identified. The total number of
      echocardiographic examinations to achieve each level of expertise remains
      unchanged from the 2002 American Society of Echocardiography and the Society of
      Cardiovascular Anesthesiologists guidelines. The increased proportion of
      examinations personally performed at basic and advanced levels, as well as the
      level of autonomy at the basic level suggested by the Quebec expert consensus are
      retained. These examinations may be performed in a perioperative setting and are
      not limited to intraoperative TEE. Training 'on-the-job', the role of the
      perioperative TEE examination, the requirements for maintenance of competence and
      the duration of training are also discussed for each level of training. The
      components of a TEE report and comprehensive TEE examination are also outlined.
      CONCLUSION: The Canadian guidelines for training in adult perioperative TEE
      reflect the unique Canadian practice profile in perioperative TEE and address the
      training requirements to obtain expertise in this field.

PMID- 17036097
TI  - Treating the right patient at the right time: Access to echocardiography in
      Canada.
AB  - The Canadian Cardiovascular Society is the national professional society for
      cardiovascular specialists and researchers in Canada. In the spring of 2004, the
      Canadian Cardiovascular Society Council formed the Access to Care Working Group
      ('Working Group') to use the best science and information available to establish
      reasonable triage categories and safe wait times for access to common
      cardiovascular procedures. The Working Group decided to publish a series of
      commentaries to initiate a structured national discussion on this important
      issue, and the present commentary proposes recommended wait times for access to
      echocardiography. 'Emergent' echocardiograms should be performed within 24 h,
      'urgent' within seven days and 'scheduled' (elective) within 30 days. A framework
      for a solution-oriented approach to improve access is presented.

PMID- 17036100
TI  - Morphological findings in 192 surgically excised native mitral valves.
AB  - INTRODUCTION: Mitral valve disease (MVD) is a significant clinical problem that
      is becoming more common in the 21st century. The pathogenesis of MVD seems to be
      changing and is not well understood. PATIENTS AND METHODS: The present study
      details the morphological findings in 192 native mitral valves excised over a one
      year period at the Toronto General Hospital, Toronto, Ontario. The mean patient
      age was 59.7+/-12.3 years at operation. RESULTS: There were 106 men (55.2%) and
      86 women (44.8%) in the present study. The most frequent changes in the
      surgically excised valvular leaflets were fibrosis (78.6%) and thickening
      (66.2%). Fusion (32.3%) and calcification (25.2%) were common changes at the
      commissures. Chordae tendineae most often showed evidence of thickening (47.9%)
      and fibrosis (37.0%). In total, 110 valves showed mitral incompetence (57.3%), 72
      showed mitral stenosis (37.5%), and 10 showed a combination of stenosis and
      incompetence (5.2%). CONCLUSIONS: In the present series, MVD was most frequently
      caused by postinflammatory (rheumatic) valve disease (RVD) (35.9%), followed by
      myxomatous degeneration (33.3%). Patients with RVD were usually female (66.7%),
      while those with myxomatous degeneration were more likely to be male (76.6%). RVD
      remains a significant problem even though the incidence of acute rheumatic fever
      with cardiac involvement has declined in Canada. This most likely reflects the
      current sociodemographic composition of the referral population.

PMID- 17036099
TI  - Timing, setting and incidence of cardiovascular complications in patients with
      acute myocardial infarction submitted to primary percutaneous coronary
      intervention.
AB  - BACKGROUND: At the Istituto di Clinica Medica Generale e Cardiologia (Florence,
      Italy), the widespread use of percutaneous coronary intervention (PCI) has
      markedly changed the hospital course of patients with acute myocardial infarction
      (AMI). These patients are typically transferred to the coronary care unit (CCU)
      only after primary PCI, whereas during the thrombolytic era, patients were first
      admitted to CCU before reperfusion. OBJECTIVES AND METHODS: The incidence, timing
      and setting of complications from symptom onset to hospital discharge in 689
      consecutive AMI patients undergoing PCI were evaluated. RESULTS: Ventricular
      fibrillation occurred in 11% of patients, and most episodes (94.7%) occurred
      before or during PCI. Of all patients, 6.3% developed complete atrioventricular
      block (CAVB), and in 86.3% of these cases, the CAVB occurred before or during
      PCI; in 94.5%, a CAVB resolution occurred in the catheterization laboratory (CL).
      Thirty-one patients (4.5%) had impending shock on admission to the CL.
      Cardiogenic shock developed in 2 9 patients (4.2%), mostly in the prehospital
      phase or in the CL. Only four patients (less than 1%) developed cardiogenic shock
      later during their hospital course. Similarly, circulatory and ventilatory
      support, as well as temporary pacing and cardiac defibrillation, were used mostly
      in the prehospital phase or in the CL. During the CCU stay, 45 patients (6.5%)
      had hemorrhagic or vascular complications, and the incidence of post-PCI ischemia
      and early reocclusion of the culprit vessel were low (2.1% and 0.6%,
      respectively). Thus, cardiac complications usually associated with AMI were
      observed mainly before hospital admission or in the CL during the reopening of
      the target vessel. These complications were rarely observed after a successful
      PCI. CONCLUSIONS: For AMI patients, the CL is not only the site of PCI, it is
      also where most life-threatening cardiac complications are observed and treated.

PMID- 17036098
TI  - Efficacy and tolerability of ezetimibe 10 mg/day coadministered with statins in
      patients with primary hypercholesterolemia who do not achieve target LDL-C while
      on statin monotherapy: A Canadian, multicentre, prospective study--the Ezetrol
      Add-On Study.
AB  - BACKGROUND: For patients who have above-target low-density lipoprotein
      cholesterol (LDL-C) levels while on statin monotherapy, coadministration of a
      cholesterol absorption inhibitor with the statin may decrease serum LDL-C levels
      and improve overall lipid profiles. OBJECTIVES: To assess the effectiveness and
      safety of ezetimibe 10 mg/day coadministered with a statin in patients with
      primary hypercholesterolemia who have higher than recommended LDL-C levels while
      on statin monotherapy. METHODS: A six-week, prospective, multicentre study of
      eligible patients who had above-target LDL-C levels while on monotherapy with any
      statin, regardless of dose, for a minimum of four weeks. All patients were
      treated for six weeks with 10 mg ezetimibe daily coadministered with their
      current statins. RESULTS: A total of 1141 patients were screened, 953 (83.5%)
      fulfilled the study inclusion criteria and 837 (87.8%) completed the study.
      Reasons for withdrawal included: lost to follow-up (50 patients [5.2%]); protocol
      violations (45 patients [4.7%]); adverse events (19 patients [2.0%]); and
      withdrawal of consent (two patients [0.2%]). After six weeks of treatment,
      statistically significant (P = 0.001) mean reductions were observed in LDL-C
      (30.05%), total cholesterol (20.84%), triglycerides (10.16%), apolipoprotein B
      (19.84%) and the total cholesterol to high-density lipoprotein cholesterol ratio
      (19.88%). At six weeks, 674 patients (80.5%) achieved target LDL-C levels. Fifty
      predominantly mild, nonserious adverse events related to ezetimibe were reported
      by 32 patients (3.4%). Frequently reported adverse events included constipation
      (n = 7 [0.7% of patients]), diarrhea (n = 4 [0.4%]) and dizziness (n = 4 [0.4%]).
      CONCLUSION: Ezetimibe coadministered with statins is effective in reducing LDL-C
      in patients who do not attain target LDL-C levels while on statin monotherapy.

PMID- 17036102
TI  - Native anomalous left coronary artery from the pulmonary artery in an adult:
      Evidence of impaired coronary flow reserve by rubidium-82 positron emission
      tomography quantification.

PMID- 17036101
TI  - Transient left ventricular dysfunction (tako-tsubo phenomenon): Findings and
      potential pathophysiological mechanisms.
AB  - Tako-tsubo-like left ventricular dysfunction phenomenon (TTP) is characterized by
      transient left ventricular apical ballooning associated with symptoms,
      electrocardiographic changes and minimal cardiac enzyme release in the absence of
      coronary artery disease. Initially described in Japan, TTP occurs worldwide,
      predominantly in women and frequently after emotional or physical stress.
      Symptoms include anginal chest pain, dyspnea and syncope. Electrocardiographic ST
      elevations may be present only for several hours, and are followed by negative T
      waves that persist for months. Arterial hypertension is found in up to 76% of TTP
      patients, hyperlipidemia in up to 57% and diabetes mellitus in up to 12%.
      Potential pathophysiological mechanisms for TTP include catecholamine-induced
      myocardial stunning or hyperkinesis of the basal left ventricular segments,
      coronary vasospasm, plaque rupture, myocarditis and genetic factors. TTP patients
      should be monitored similarly to myocardial infarction patients because organ
      failure, cardiogenic shock, ventricular fibrillation or rupture may occur. Beta
      blockers are indicated, whereas catecholamines and nitrates should be avoided.
      The long-term prognosis is unknown.

PMID- 17036104
TI  - Biaryl synthesis with control of axial chirality.
AB  - Biaryls have been a persistent focus of interest for chemists since it was
      recognised, more than 80 years ago, that they can manifest the axial chirality
      that is inherent in structures consisting of intersecting dissymmetric planes. In
      recent decades their importance has risen steeply as this structural motif proved
      spectacularly successful in catalytic synthetic roles and was found to be
      significant in the context of biological activity. As a consequence, synthetic
      methods which allowed the construction of biaryls with axial stereocontrol have
      become highly desirable, and this article traces the development of non
      resolution approaches to biaryls with a chosen axial configuration.

PMID- 17036103
TI  - Left main coronary artery thrombectomy and stenting using a paclitaxel-eluting
      stent in the setting of acute myocardial infarction.
AB  - A 41-year-old man was referred to the Montreal Heart Institute, Montreal, Quebec,
      for primary angioplasty of an acute anterolateral wall myocardial infarction.
      Coronary angiography revealed the culprit lesion to be a subtotal left main
      coronary artery with Thrombolysis In Myocardial Infarction (TIMI) trial grade 1
      flow associated with a filling defect compatible with an aggressive thrombotic
      process. The use of rheolytic thrombectomy and a drug-eluting stent for this
      distal left main target lesion are described.

PMID- 17036105
TI  - Synthesis and anticancer activity studies of alpha-aminoalkylated conjugated
      nitroalkenes.
AB  - Novel alpha-aminoalkylated conjugated nitroalkenes which inhibit human cervical
      cancer (HeLa) cell proliferation by binding to tubulin were synthesized by
      imidazole/LiCl-mediated reaction of conjugated nitroalkenes with N-tosylimines.

PMID- 17036106
TI  - First total synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3
      formyl-7-hydroxycarbazole, clausine M, clausine N and the anti-HIV active
      siamenol using a highly efficient palladium-catalyzed approach.
AB  - Using a convergent palladium-catalyzed construction of the carbazole framework as
      the key step we have achieved a short synthesis of the 7-oxygenated carbazole
      alkaloids clauszoline-K, 3-formyl-7-hydroxycarbazole, clausine C (clauszoline-L),
      clausine M, clausine N and the anti-HIV active siamenol.

PMID- 17036107
TI  - Two-directional synthesis and stereochemical assignment toward a C2 symmetric
      oxasqualenoid (+)-intricatetraol.
AB  - The asymmetric synthesis of tetraol (+)-3, a degradation product derived from a
      C2 symmetric oxasqualenoid intricatetraol 1, has been achieved through the two
      directional synthesis starting from diol 7, realizing the further additional
      assignment of the incomplete stereostructure of 1, the stereochemistry of which
      is difficult to determine otherwise.

PMID- 17036108
TI  - Silenes in organic synthesis: a short synthesis of prelactone B.
AB  - A sequence involving dihydroxylation and acid induced fragmentation of silene
      generated silacyclohexenes represents the key step in a concise synthetic route
      to beta-hydroxy-delta-lactones.

PMID- 17036109
TI  - First synthesis of 1,2,3-triazolo-linked (1,6)-alpha-D-oligomannoses
      (triazolomannoses) by iterative Cu(I)-catalyzed alkyne-azide cycloaddition.
AB  - The iterative copper(I)-catalyzed cycloaddition (rt or microwave) between an
      ethynyl alpha-C-mannoside and alkyl 6-azido-alpha-C-mannoside derivatives was
      suited to the (1,6)-ligation between alpha-D-mannose units through 1,4
      disubstituted triazole bridges, thus resulting in the formation of linear
      oligomers (80-90% yield) with alternating triazole and mannose fragments up to a
      triazolo-pentamannose derivative.

PMID- 17036110
TI  - Synthesis of bisindolylmaleimides related to GF109203x and their efficient
      conversion to the bioactive indolocarbazoles.
AB  - From a structure-activity relationship perspective, the new indolocarbazoles 11
      and 12 have been synthesized and evaluated biologically as novel Chk1 inhibitors.
      Compounds 11 and 12 were synthesized in high yield from indole via
      bisindolylmaleimides 18 and 24.

PMID- 17036111
TI  - Rhodium-catalysed addition of organotrialkoxysilanes to alpha-substituted acrylic
      esters.
AB  - The cationic rhodium complex [Rh(cod)2][BF4] effectively catalyses the 1,4
      addition of organotrialkoxysilanes to alpha-substituted acrylic esters. The
      reactions are promoted by heating in an oil-bath or more conveniently in a
      microwave reactor allowing rapid access to a useful range of functionalised
      products including 2-alkyl succinates and alpha-amino acid derivatives.

PMID- 17036112
TI  - Reproducibility and transferability of topological data: experimental charge
      density study of two modifications of L-alanyl-L-tyrosyl-L-alanine.
AB  - Two crystalline modifications of the tripeptide L-Ala-L-Tyr-L-Ala, which have
      different solvent molecules in the crystal structure (water and ethanol for
      modifications 1 and 2), were the subject of experimental charge density studies
      based on high resolution X-ray data collected at ultra-low temperatures of 9 K
      (1) and 20 K (2), respectively. The molecular structures and the intermolecular
      interactions were found to be rather similar in the two crystal lattices, so that
      this study allowed the reproducibility of the charge density of a given molecule
      in different (but widely comparable) crystalline environments to be examined.
      With respect to bond topological and atomic properties, the agreement between the
      two modifications of the title tripeptide was in the same range as found from the
      comparison with the previously reported results of tri-L-alanine. It follows that
      the reproducibility and transferability of quantitative topological data are
      comparable and that within the accuracy of experimental charge density work the
      replacement of the central amino acid residue L-Ala by L-Tyr has no significant
      influence, neither on bond nor on the atomic properties of the oligopeptide main
      chain. Intermolecular interactions in the form of hydrogen bonds were
      characterized quantitatively and qualitatively by topological criteria and by
      mapping the charge density distribution on the Hirshfeld surface.

PMID- 17036113
TI  - The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives
      as potent non-nucleoside inhibitors of HIV reverse transcriptase.
AB  - Novel compounds, which can be considered as conformationally restricted analogues
      of MKC-442, have been synthesized and tested as inhibitors of the reverse
      transcriptase of human immunodeficiency virus type-1 (HIV-1). Reaction of urea
      with a beta-ketoester furnished 6,7,8,9-tetrahydro-9-phenyl-1H
      cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6a) and 6,7,8,9-tetrahydro-9-p-tolyl
      1H-cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6b) which were then alkylated at
      the N-1 position with chloromethyl ether, allyl bromide and benzyl bromide to
      afford the target compounds 7a-b, 8a-b, 9 and 10, respectively. The seven
      membered, annelated compounds have a relatively rigid structures and can lock the
      orientation of the aromatic ring. Chemical modification at N-1 of the pyrinidine
      ring and the 9-phenyl ring was attempted, with the aim of improving the
      antiretroviral activity. In particular, replacement of the aliphatic group with
      the phenyl moiety at the terminus of N-1 side chain can enhance the activity. The
      most active compounds showed activity in the low micromolar range with IC50
      values comparable to that of nevirapine. The biological activity results are in
      accordance with the docking results.

PMID- 17036115
TI  - Artificial aldolases from peptide dendrimer combinatorial libraries.
AB  - Peptide dendrimers were investigated as synthetic models for aldolase enzymes.
      Combinatorial libraries were prepared with aldolase active residues such as
      lysine and proline placed at the dendrimer core or near the surface. On-bead
      selection for aldolase activity was carried out using the dye-labelled 1,3
      diketone 1a, suitable for covalent trapping of enamine-reactive side-chains, and
      the fluorogenic enolization probe 6. Aldolase dendrimers catalyzed the aldol
      reaction of acetone, dihydroxyacetone and cyclohexanone with nitrobenzaldehyde.
      Much like enzymes, the dendrimers exhibited strong aldolase activity in aqueous
      medium, but were also active in organic solvent. Dendrimer-catalyzed aldol
      reactions reached complete conversion in 3 h at 25 degrees C with 1 mol% catalyst
      and gave aldol products with up to 65% ee. A positive dendritic effect in
      catalysis was observed with both lysine and proline based aldolase dendrimer
      catalysts.

PMID- 17036114
TI  - Synthesis and optimization of peptidomimetics as HIV entry inhibitors against the
      receptor protein CD4 using STD NMR and ligand docking.
AB  - We recently described the design and synthesis of a novel CD4 binding
      peptidomimetic as a potential HIV entry inhibitor with a KD value of
      approximately 35 microM and a high proteolytic stability [A. T. Neffe and B.
      Meyer, Angew. Chem., Int. Ed., 2004, 43, 2937-2940]. Based on saturation transfer
      difference (STD) NMR analyses and docking studies of peptidomimetics we now
      report the rational design, synthesis, and binding properties of 11 compounds
      with improved binding affinity. Surface plasmon resonance (SPR) resulted in a KD
      = 10 microM for the best peptidomimetic XI, whose binding affinity is confirmed
      by STD NMR (KD = 9 microM). The STD NMR determined binding epitope of the ligand
      indicates a very similar binding mode as that of the lead structure. The binding
      studies provide structure activity relationships and demonstrate the utility of
      this approach.

PMID- 17036116
TI  - Reactions of indoles with nitrogen dioxide and nitrous acid in an aprotic
      solvent.
AB  - The reaction of 2-phenyl- and 1-methyl-2-phenylindole with nitrogen dioxide or
      with nitrous acid (NaNO2-CH3COOH) in benzene leads mainly to the formation of the
      isonitroso and 3-nitroso indole derivatives, respectively. When reacted with
      nitrous acid, 1-methyl-2-phenylindole gives also the corresponding azo-bis-indole
      in good yields. The reaction of indole with nitrogen dioxide leads to 2-(indol-3
      yl)-3H-indol-3-one as the main product together with small amounts of 2-(indol-3
      yl)-3H-indol-3-oxime; whereas the major product obtained when the same indole is
      reacted with nitrous acid is represented by 2-(indol-3-yl)-3H-indol-3-oxime. The
      reaction of 3-alkyl substituted indoles with nitrogen dioxide is rather complex
      and results in the formation of different nitro indoles, whereas nitrosation is
      observed when nitrous acid is used. Crystal structures of 2-(indol-3-yl)-3H-indol
      3-one and of 4-nitro-N-acetyltryptamine have been determined by X-ray analysis.

PMID- 17036117
TI  - A practical synthetic route to functionalized THBCs and oxygenated analogues via
      intramolecular Friedel-Crafts reactions.
AB  - A practical catalytic approach to the synthesis of 4-substituted 1,2,3,4
      tetrahydro-beta-carbolines (THBCs, 1) and 1,2,3,9-tetrahydropyrano[3,4-b]indoles
      (2) via InBr3-catalyzed intramolecular Friedel-Crafts (F-C) cyclization is
      described. The use of cross-metathesis reaction represents a direct route to the
      cyclization precursors and the use of InBr3 (5 mol%) allowed polycyclic indole
      compounds to be isolated in high yields under mild reaction conditions (rt, DCM,
      minutes). Finally, efforts toward the development of a stereocontrolled version
      of the present cyclization are presented, highlighting [salenAlCl] and bimetallic
      [(salenAlCl)2-InBr3] system as promising chiral Lewis acids (ee up to 60%).

PMID- 17036118
TI  - Synthesis and structure of bifunctional N-alkylbenzimidazole phenylboronate
      derivatives.
AB  - N-Methyl and N-n-butyl-2-(2-boronophenyl)benzimidazoles are accessed from the
      corresponding mono-N-alkyl-ortho-phenylenediamines, either using a polyphosphoric
      acid-mediated cyclisation with ortho-bromobenzoic acid, or preferably using an
      Oxone-mediated cyclisation of the corresponding aldehyde, followed by a lithium
      exchange and borylation sequence. The resulting boronic acids show unusual
      physical and chemical properties, as shown by 11B NMR and X-ray crystallography.

PMID- 17036119
TI  - Synthesis of 1-beta-O-acyl glucuronides of diclofenac, mefenamic acid and (S)
      naproxen by the chemo-selective enzymatic removal of protecting groups from the
      corresponding methyl acetyl derivatives.
AB  - Using a straightforward chemo-enzymatic procedure, 1-beta-O-acyl glucuronides of
      three non-steroidal anti-inflammatory drugs, diclofenac (DF) 5, mefenamic acid
      (MF) 6 and (S)-naproxen (NP) 7, were prepared. Caesium salts of these carboxylic
      acid drugs reacted with commercially available methyl 2,3,4-tri-O-acetyl-1-bromo
      1-deoxy-alpha-D-glucopyranuronate 4 to give exclusively the corresponding 1-beta
      O-acyl glucuronides 8-10 in moderate yields. The protecting acetyl (for -OH
      group) and methyl ester (for -CO2H group) groups of each sugar moiety were easily
      removed to provide the corresponding free 1-beta-O-acyl glucuronides 1-3 in high
      yields. Deprotection was achieved through effective enzyme-catalysed chemo
      selective hydrolyses of the acetyl groups using lipase AS Amano (LAS), and of the
      methyl ester group using esterase from porcine liver (PLE).

PMID- 17036121
TI  - Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium
      complex in water.
AB  - Hydrophobic Frechet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III)
      complexes have been applied in the asymmetric transfer hydrogenation of ketones
      in water using HCOONa as hydrogen source. The catalysts were found to be finely
      dissolved in the liquid substrates in the aqueous mixture and exhibited high
      catalytic activity and enantioselectivity (52-97% ee). The catalytic loading
      could be decreased to 0.01 mol% and good conversion was still obtained with
      excellent enantioselectivity. Moreover, the catalyst could be easily precipitated
      from the mixture by adding hexane and reused several times without affecting the
      high enantioselectivity.

PMID- 17036122
TI  - Synthesis of the C1-C16 fragment of ionomycin using a neutral (eta3-allyl)iron
      complex.
AB  - Key steps in the synthesis of the C1-C16 polyketide fragment of ionomycin were
      the nucleophilic addition of an organocuprate to a neutral (eta3-allyl)iron
      complex and the construction of a beta-diketone moiety by the Rh-catalysed
      rearrangement of an alpha-diazo-beta-hydroxyketone.

PMID- 17036120
TI  - Total synthesis of enantiopure 1,3-dimethylpyranonaphthoquinones including
      ventiloquinones E, G, L and eleutherin.
AB  - A new synthetic approach to enantiopure pyranonaphthoquinones is described. (S)
      Mellein 10, prepared in 6 steps from (S)-propylene oxide 16, is converted
      stereospecifically to the (1R,3S)-dimethylpyran 15. The pyran 15 is then
      converted to the benzoquinone 14, which undergoes regiospecific Diels-Alder
      reactions with a variety of oxygenated butadienes to give pyranonaphthoquinones
      including ventiloquinones E, G, L, eleutherin and ent-deoxyquinone A.

PMID- 17036123
TI  - Synthesis and G-quadruplex binding studies of new 4-N-methylpyridinium
      porphyrins.
AB  - A series of cationic porphyrins carrying 1-3 meso-N-pyridinium groups has been
      synthesised, and their binding to G-quadruplex DNA has been explored by surface
      plasmon resonance (SPR) and circular dichroism spectroscopy. Two trans
      substituents appear to be sufficient for tight binding; preferential binding to
      the anti-parallel intramolecular human telomeric DNA was observed for the A2trans
      and A3 porphyrins. The A2trans is able to induce the formation of an anti
      parallel G-quadruplex in a K+ free solution, mimicking the effect of a molecular
      chaperone.

PMID- 17036124
TI  - Dioxygenase-catalysed oxidation of disubstituted benzene substrates: benzylic
      monohydroxylation versus aryl cis-dihydroxylation and the meta effect.
AB  - Biotransformations of a series of ortho-, meta- and para-substituted ethylbenzene
      and propylbenzene substrates have been carried out, using Pseudomonas putida UV4,
      a source of toluene dioxygenase (TDO). The ortho- and para-substituted
      alkylbenzene substrates yielded, exclusively, the corresponding enantiopure cis
      dihydrodiols of the same absolute configuration. However, the meta isomers,
      generally, gave benzylic alcohol bioproducts, in addition to the cis-dihydrodiols
      (the meta effect). The benzylic alcohols were of identical (R) absolute
      configuration but enantiomeric excess values were variable. The similar (2R)
      absolute configurations of the cis-dihydrodiols are consistent with both the
      ethyl and propyl groups having dominant stereodirecting effects over the other
      substituents. The model used earlier, to predict the regio- and stereo-chemistry
      of cis-dihydrodiol bioproducts derived from substituted benzene substrates has
      been refined, to take account of non-symmetric substituents like ethyl or propyl
      groups. The formation of benzylic hydroxylation products, from meta-substituted
      benzene substrates, without further cis-dihydroxylation to yield triols provides
      a further example of the meta effect during toluene dioxygenase-catalysed
      oxidations.

PMID- 17036125
TI  - New 64Cu PET imaging agents for personalised medicine and drug development using
      the hexa-aza cage, SarAr.
AB  - The success of positron emission tomography (PET) in personalised medicine and
      drug development requires radioisotopes that provide high quality images and
      flexible chemistry for a broad application. 64Cu is arguably one of the most
      suitable PET isotopes for imaging with the evolving target agents, but there are
      not many appropriate chelating agents for 64Cu and this has limited its wider
      application. The bi-functional chelator, SarAr is known to bind 64Cu2+
      quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10(-6)
      M over a range of pH (4-9). In this paper the conjugation of SarAr to the whole
      and fragmented antibody is described. Conjugation of the SarAr to the protein
      does not impair its coordination of the 64Cu. It complexes the 64Cu2+ rapidly,
      quantitatively and essentially irreversibly at pH 5. Animal studies show that the
      64Cu-SarAr-immunoconjugates maintain their specificity for the target and are
      stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit
      formulation and is readily adaptable for the wider application in 64Cu PET
      imaging.

PMID- 17036126
TI  - Phenol quaternary ammonium derivatives: charge and linker effect on their DNA
      photo-inducible cross-linking abilities.
AB  - We report here that phenol derivatives with two and four quaternary ammoniums
      were synthesized and their abilities to bind and cross-link DNA were
      investigated. Thermal denaturizing studies indicated that derivatives possess
      similar DNA binding abilities and gel electrophoresis revealed that more charges
      (series B) and electronic donation substitute linkers (like -S-) dramatically
      increase the DNA cross-linking abilities.

PMID- 17036127
TI  - Editorial: DNA-based nanoarchitectures and nanomachines.
AB  - The emerging area of DNA-based architectures and machines promises exciting
      opportunities and will impact on the future of DNA structures in
      nanobiotechnology.

PMID- 17036128
TI  - DNA nanomachines and nanostructures involving quadruplexes.
AB  - DNA is an attractive component for molecular recognition, because of its self
      assembly properties. Its three-dimensional structure can differ markedly from the
      classical double helix. For example, DNA or RNA strands carrying guanine or
      cytosine stretches associate into four-stranded structures called G-quadruplexes
      or i-DNA, respectively. Since 2002, several groups have described nanomachines
      that take advantage of this structural polymorphism. We first introduce the
      unusual structures that are involved in these devices (i.e., i-DNA and G
      quadruplexes) and then describe the opening and closing steps that allow cycling.
      A quadruplex-duplex molecular machine is then presented in detail, together with
      the rules that govern its formation, its opening/closing kinetics and the various
      technical and physico-chemical parameters that play a role in the efficiency of
      this device. Finally, we review the few examples of nanostructures that involve
      quadruplexes.

PMID- 17036129
TI  - DNA-based machines.
AB  - Nucleic acids include substantial information in their base sequence and their
      hybridization-complexation motifs. Recent research efforts attempt to utilize
      this biomolecular information to develop DNA nanostructures exhibiting machine
      like functions. DNA nano-assemblies revealing tweezers, motor, and walker
      activities exemplify a few such machines. The DNA-based machines provide new
      components that act as sensitive sensors, transporters, or drug delivery systems.

PMID- 17036130
TI  - Combinatorial self-assembly of DNA nanostructures.
AB  - Here we report a modular design of self-assembly of DNA nanostructures in a
      combinatorial approach; a square with approximately 25 nm cavity dimension, a
      chair with approximately 80 nm in height and a line with approximately 100 nm in
      length are formed through combinations of four cross-shaped DNA tiles which are
      kept constant and six variable linker tiles.

PMID- 17036131
TI  - Preparation of branched structures with long DNA duplex arms.
AB  - Branched structures with long DNA duplex arms have been constructed through
      biotin-streptavidin binding and characterized by gel electrophoresis and atomic
      force microscopy (AFM) imaging.

PMID- 17036132
TI  - Molecular design of novel non-planar heteropolycyclic fluorophores with bulky
      substituents: convenient synthesis and solid-state fluorescence characterization.
AB  - Novel indeno[1,2-b]benzo[4,5-e]pyran-11-one-type fluorophores exhibiting intense
      solid-state fluorescence were conveniently synthesized and the relation between
      their solid-state photophysical properties and the X-ray crystal structures were
      investigated, which demonstrates that non-planar structures with sterical
      hindered substituents prevent the fluorophores from forming short pi-pi contacts
      causing fluorescence quenching in the solid state.

PMID- 17036133
TI  - New ortho-quinone methide formation: application to three-component coupling of
      isocyanides, aldehydes and phenols.
AB  - Herein, we wish to report a new three-component formation of heterocyclic
      scaffolds based on a one-pot process from simple phenols. The key step of this
      procedure involves an ortho-quinone methide formation from Mannich adducts under
      alkylative conditions. The transient o-quinone methide has been trapped in situ
      with indole and diketone using lithium perchlorate as catalyst. The interest of
      this procedure has been furthermore demonstrated by a new three-component
      aminobenzofuran formation from phenols, aldehydes and isocyanides.

PMID- 17036134
TI  - Double cohesion in structural DNA nanotechnology.
AB  - Double cohesion has proved to be a useful tool to assemble robust 2D arrays of
      large tiles. Here we present a variety of examples showing the utility of this
      approach. We apply this principle to the 3 types of 2D lattice sections of arrays
      whose individual tiles are inherently 3 dimensional, because they contain three
      vectors that span 3-space. This application includes motifs which are based on
      the tensegrity triangle, the six-helix bundle motif and on three skewed triple
      crossover molecules. All of these designs have the potential to form 3
      dimensional structures if all three directions of propagation are allowed. If one
      direction is blunted, 2D arrays form, and all 3 combinations are presented here.
      In addition, a large parallelogram array that was not attainable previously using
      single duplex cohesion was also constructed using double cohesion. For
      comparison, arrays which use another type of double cohesion, double paranemic
      (PX) cohesion are also presented. Double cohesion of sticky ends proved to be the
      more effective tool to assemble large motifs into arrays.

PMID- 17036136
TI  - Characterization and modulation of the hierarchical self-assembly of
      nanostructured DNA tiles into supramolecular polymers.
AB  - We present a set of DNA supramolecular architectures based on the polymerization
      of discrete DNA tiles having the shape of parallelograms and designed to have a
      one-dimensional inter-tile connectivity. Tiles bind to each other with two
      connections, which have different thermal stabilities. We discuss how this
      difference in stability implies that the same monomeric tile can yield
      supramolecular polymers of different shapes just by changing the polymerization
      conditions. We show how this system reacts to external stimuli by interconverting
      between some of its possible states. Concurrently, we show how performing the
      polymerization on a surface can influence its outcome.

PMID- 17036135
TI  - Single-chain antibodies against DNA aptamers for use as adapter molecules on DNA
      tile arrays in nanoscale materials organization.
AB  - Complex DNA nanostructures have been developed as structural components for the
      construction of nanoscale objects. Recent advances have enabled self-assembly of
      organized DNA nanolattices and their use in patterning functional bio
      macromolecules and other nanomaterials. Adapter molecules that bind specifically
      to both DNA lattices and nanomaterials would be useful components in a molecular
      construction kit for patterned nanodevices. Herein we describe the selection from
      phage display libraries of single-chain antibodies (scFv) for binding to a
      specific DNA aptamer and their development as adapter molecules for nanoscale
      construction. We demonstrate the decoration of various DNA tile structures with
      aptamers and show binding of the selected single-chain antibody as well as the
      self-assembly of mixed DNA-protein biomolecular lattices.

PMID- 17036137
TI  - Design of asymmetric DNAzymes for dynamic control of nanoparticle aggregation
      states in response to chemical stimuli.
AB  - Dynamic control of nanomaterial assembly states in response to chemical stimuli
      is critical in making multi-component materials with interesting properties.
      Previous work has shown that a Pb2+-specific DNAzyme allowed dynamic control of
      gold nanoparticle aggregation states in response to Pb2+, and the resulting color
      change from blue aggregates to red dispersed particles can be used as a
      convenient way of sensing Pb2+. However, a small piece of DNA (called invasive
      DNA) and low ionic strength (approximately 30 mM) were required for the process,
      limiting the scope of application in assembly and sensing. To overcome this
      limitation, a series of asymmetric DNAzymes, in which one of the two substrate
      binding regions is longer than the other, has been developed. With such a system,
      we demonstrated Pb2+-induced disassembly of gold nanoparticle aggregates and
      corresponding color change at room temperature without the need for invasive DNA,
      while also making the system more tolerant to ionic strength (33-100 mM). The
      optimal lengths of the long and short arms were determined to be 14 and 5 base
      pairs, respectively. In nanoparticle aggregates, the activity of the DNAzyme
      increased with decreasing ionic strength of the reaction buffer. This simpler and
      more versatile system allows even better dynamic control of nanoparticle
      aggregation states in response to chemical stimuli such as Pb2+, and can be used
      in a wider range of applications for colorimetric sensing of metal ions.

PMID- 17036138
TI  - Synthesis of an elongated linear oligo(phenylene ethynylene)-based building block
      for application in DNA-programmed assembly.
AB  - The synthesis of an elongated linear oligonucleotide-functionalised module (ELOM)
      is described. The ELOM structure is based on an oligo(phenylene ethynylene)
      backbone substituted with two decyloxy groups. The two termini constitute two
      salicylaldehyde moieties acting as chemical cross-linkers. Before incorporation
      into an oligonucleotide sequence the organic part of the module, the elongated
      linear module (ELM), is functionalised with a dimethoxytrityl group and a
      phosphoramidite group. This enables incorporation into the middle of 30-mer
      oligonucleotide sequences by automated DNA synthesis. The obtained ELOMs were
      characterised by polyacrylamide gel electrophoresis and MALDI-TOF mass
      spectrometry. In analogy with previously reported LOM and TOM structures the
      coupling reactions of the ELOM modules were tested.

PMID- 17036139
TI  - Electrical manipulation of oligonucleotides grafted to charged surfaces.
AB  - The electrical manipulation of short DNA molecules on surfaces offers novel
      functionalities with fascinating possibilities in the field of bio-interfaces.
      Here we present systematic investigations of the electrical interactions which
      govern the structure of oligonucleotides on charged gold surfaces. Successively,
      we address influences of the applied field strength, the role of DC electrode
      potentials, in particular for polycrystalline surfaces, as well as screening
      effects of the surrounding electrolyte solution. Data obtained for single and
      double stranded DNA exhibit differences which can be attributed to the dissimilar
      flexibility of the different molecular conformations. A comparison of the
      experimental results with a basic model shows how the alignment of the molecules
      adjusts according to a balance between electrically induced ordering and
      stochastic thermal motions. The presented conclusions are expected to be of
      general relevance for the behaviour of polyelectrolytes exposed to localized
      electric fields at interfaces.

PMID- 17036140
TI  - Non-enzymatic reduction of quinone methides during oxidative coupling of
      monolignols: implications for the origin of benzyl structures in lignins.
AB  - Lignin is believed to be synthesized by oxidative coupling of 4
      hydroxyphenylpropanoids. In native lignin there are some types of reduced
      structures that cannot be explained solely by oxidative coupling. In the present
      work we showed via biomimetic model experiments that nicotinamide adenine
      dinucleotide (NADH), in an uncatalyzed process, reduced a beta-aryl ether quinone
      methide to its benzyl derivative. A number of other biologically significant
      reductants, including the enzyme cellobiose dehydrogenase, failed to produce the
      reduced structures. Synthetic dehydrogenation polymers of coniferyl alcohol
      synthesized (under oxidative conditions) in the presence of the reductant NADH
      produced the same kind of reduced structures as in the model experiment,
      demonstrating that oxidative and reductive processes can occur in the same
      environment, and that reduction of the in situ-generated quinone methides was
      sufficiently competitive with water addition. In situ reduction of beta-beta
      quinone methides was not achieved in this study. The origin of racemic benzyl
      structures in lignins therefore remains unknown, but the potential for simple
      chemical reduction is demonstrated here.

PMID- 17036141
TI  - Homogeneous enzymatic reactions in ionic liquids with poly(ethylene glycol)
      modified subtilisin.
AB  - Subtilisin Carlsberg was covalently modified with comb-shaped poly(ethylene
      glycol) (PM13). PM13-modified subtilisin (PM13-Sub) was readily solubilized in
      three different ionic liquids (ILs), i.e., [Emim][Tf2N], [C2OC1mim][Tf2N] and
      [C2OHmim][Tf2N]. Analysis of homogeneous enzymatic reactions in the ILs revealed
      that PM13-Sub exhibited excellent catalytic performance while the native enzyme
      suspended in ILs showed no activity. Hydrophobicity of ILs slightly affected
      enzyme activity, and the relatively hydrophobic IL [Emim][Tf2N] was the preferred
      medium for enzymatic reactions, similar to enzymatic reactions in conventional
      organic solvents. Enzyme activity was much higher in [Emim][Tf2N] than in
      conventional organic solvents, and excellent activity was associated with unique
      properties of ILs such as hydrophobicity and high polarity. Furthermore, PM13-Sub
      showed good stability in [Emim][Tf2N], and maintained 80% of its initial activity
      after 60 h.

PMID- 17036142
TI  - A combined molecular dynamics simulation and quantum chemical study on the
      mechanism for activation of the OxyR transcription factor by hydrogen peroxide.
AB  - Molecular dynamics (MD) simulations have been performed on the regulatory domain
      of the Escherichia coli OxyR transcription factor for the different chemical
      states along the mechanistic cycle for its activation by hydrogen peroxide.
      Conformational analysis indicates that His198 and Arg220 catalytic residues can
      be involved in the biochemical process of activation of OxyR. On the basis of the
      simulation data, a detailed mechanism for the oxidation process is suggested in
      which His198, in the presence of an arginine residue, functions as a unique acid
      base catalyst in the successive oxidations of Cys199 and Cys208 by hydrogen
      peroxide. This mechanistic proposal has been tested by density functional theory
      (DFT-B3LYP) and ab initio (MP2) calculations on model systems. The two oxidations
      are both identified as nucleophilic substitution reactions of SN2 type with
      deprotonated cysteines functioning as nucleophiles. Both reactions have a
      calculated free energy of activation close to 15 kcal mol-1, which is consistent
      with the available experimental data on the kinetics of the activation process.

PMID- 17036143
TI  - Synthesis of distamycin A polyamides targeting G-quadruplex DNA.
AB  - A number of amide-linked oligopyrroles based on distamycin molecules have been
      synthesized by solid-state methods, and their interactions with a human
      intramolecular G-quadruplex have been measured by a melting procedure. Several of
      these molecules show an enhanced ratio of quadruplex vs. duplex DNA binding
      compared to distamycin itself, including one with a 2,5-disubstituted pyrrole
      group. Quadruplex affinity increases with the number of pyrrole groups, and it is
      suggested that this is consistent with a mixed groove/G-quartet stacking binding
      mode.

PMID- 17036145
TI  - Concise access to indolizidine and pyrroloazepine skeleta via intramolecular
      Schmidt reactions of azido 1,3-diketones.
AB  - Readily prepared 2-alkyl-2-azidopropylcycloalkyl-1,3-diones undergo
      intramolecular Schmidt rearrangement with a range of hard Lewis acids, leading to
      indolizidinediones and pyrroloazepinediones. Chiral aluminium-based Lewis acids
      could also be used to mediate this symmetry-breaking transformation, but no
      significant asymmetric induction was observed.

PMID- 17036144
TI  - MAGfect: a novel liposome formulation for MRI labelling and visualization of
      cells.
AB  - Cellular entry of imaging probes, such as contrast agents for magnetic resonance
      imaging (MRI), is a key requirement for many molecular imaging studies,
      particularly imaging intracellular events and cell tracking. Here, we describe
      the successful development and in vitro analysis of MAGfect, a novel liposome
      formulation containing a lipidic gadolinium contrast agent for MRI, Gd-DOTA-Chol
      , designed to enter and label cells. Liposome formulation and cell incubation
      time were optimised for maximum cellular uptake of the imaging probe in a variety
      of cell lines. MRI analysis of cells incubated with MAGfect showed them to be
      highly MRI active. This formulation was examined further for cytotoxicity, cell
      viability and mechanism of cell labelling. One of the key advantages of using
      MAGfect as a labelling vehicle arises from its potential for additional
      functions, such as concomitant drug or gene delivery and fluorescent labelling.
      The gadolinium liposome was found to be an effective vehicle for transport of
      plasmid DNA (pDNA) into cells and expression levels were comparable to the
      commercial transfection agent Trojene.

PMID- 17036146
TI  - Supramolecular complexes of spin-labelled cyclodextrins.
AB  - EPR spectra of cyclodextrins labelled with TEMPO derivatives (SL-CDs) are
      sensitive to complexation with large guest molecules. We used SL-CDs to explore
      the behaviour of concentrated PEG/PPG solutions. The relationship between
      rotational correlation times and solvent viscosity showed significant deviations
      from the Debye-Stokes-Einstein equation, probably due to self-aggregation of
      alkylene glycols in concentrated solutions. The data fit the fractional Debye
      Stokes-Einstein equation well. We have also studied complexation of SL-CDs with
      adamantane-functionalised DAB dendrimers. The strength of binding increases with
      dendrimer generation; formation of supramolecular aggregates at high
      concentrations was observed with the generation 3 dendrimer.

PMID- 17036147
TI  - The different electronic natures displayed by the alkylthio groups in simple and
      higher conjugated aniline systems.
AB  - Systematic studies based on 1H NMR and 13C NMR indicated that the alkylthio group
      behaves as a weak electron-withdrawing group in a simple aniline system like 2
      butylthioaniline, while the same alkylthio group clearly acted as a resonance
      electron-donating group in higher conjugated aniline trimer systems, like
      butylthio-substituted PDA (mono-PDA) and dibutylthio-substituted PDA (2,6-diPDA).
      The formation of 2,6-diPDA as the major byproduct during the preparation of mono
      PDA from PDI and butane-1-thiol provided additional support for the resonance
      electron donating nature of the butylthio group in these aniline trimer systems.
      Furthermore, CV studies also clearly indicated that the redox potential E degrees
      (vs. SCE) of the aniline trimer systems decreased with the increase in the number
      of butylthio groups, further confirming the electron-donating nature of the
      butylthio group in these higher conjugated trimer systems.

PMID- 17036148
TI  - Discovery of aspoquinolones A-D, prenylated quinoline-2-one alkaloids from
      Aspergillus nidulans, motivated by genome mining.
AB  - Motivated by the observation that the Aspergillus nidulans genome bears multiple
      anthranilic acid synthase gene copies, the fungal metabolome was reinvestigated
      under various fermentation conditions, resulting in the discovery of novel
      prenylated quinolin-2-one alkaloids, two of which bear unprecedented terpenoid
      side chains.

PMID- 17036149
TI  - A short enantioselective total synthesis of the phytotoxic lactone herbarumin
      III.
AB  - The phytotoxic lactone herbarumin III has been synthesized in 11% overall yield.
      The approach applied uses Keck's asymmetric allylation and Sharpless epoxidation
      to build the key fragment. Esterification with 5-hexenoic acid and a ring closing
      metathesis was used to arrive at the target.

PMID- 17036150
TI  - Metabolism of the crucifer phytoalexins wasalexin A and B in the plant pathogenic
      fungus Leptosphaeria maculans.
AB  - Wasalexins A and B are crucifer phytoalexins produced by two substantially
      different plant species, a wild species abundant in the Canadian prairies and a
      condiment plant widely cultivated in Japan. Interestingly, both plant species are
      resistant to an economically important fungal plant pathogen, the blackleg fungus
      [Leptosphaeria maculans (Desm.) Ces. et de Not., asexual stage Phoma lingam (Tode
      ex Fr.) Desm.]. The transformation of wasalexins A and B in cultures of isolates
      of L. maculans, an isolate highly virulent towards canola (BJ 125) and a less
      common isolate which is virulent towards wasabi (Laird 2/Mayfair 2) was
      investigated. It was established that both fungal isolates are able to
      efficiently metabolize and detoxify wasalexins A and B through reduction in the
      case of wasalexin A or through hydrolysis followed by reduction in the case of
      wasalexin B. Moreover, a close structural analogue of wasalexins, which does not
      occur naturally, was also found to be reduced in cultures of L. maculans. The
      structures of the new metabolic products were elucidated using spectroscopic
      methods and were confirmed by synthesis. Bioassays indicated that the
      biotransformation of wasalexins is a detoxification process that may contribute
      to the aggressive nature of these fungal isolates towards plants that produce
      wasalexins.

PMID- 17036151
TI  - Prevalence of respiratory viruses, including newly identified viruses, in
      hospitalised children in Austria.
AB  - The aim of this epidemiological study was to determine the prevalence of
      respiratory viruses, including new viruses, in hospitalised children in Austria.
      Two hundred fourteen nasopharyngeal samples from hospitalised children were
      tested for the presence of viruses using cell culture and PCR and/or viral
      antigen assays. The results revealed a parainfluenza virus 1 (PIV1) outbreak that
      ended right before the onset of the influenza season, with nearly no overlapping,
      moderate respiratory syncytial virus (RSV) activity, and only a few adenoviruses.
      Human metapneumovirus (hMPV) was present in 14.5% of the total samples but was
      detected in combination with other viruses in only five cases: with PIV1 in three
      cases and with RSV in two cases. There were no cases of dual infection with hMPV
      and flu or adenovirus. This suggests that hMPV alone is a leading cause of
      hospitalisation in children under 1 year of age. Interestingly, hMPV, in contrast
      to RSV, coincided with PIV1 but was absent during the community outbreak of the
      flu. Samples were also tested for Mimiviridae, a group of newly described DNA
      viruses that are similar to Legionella spp., replicate in water amoebae, and also
      have been found in alveolar cells. However, mimivirus was detected neither in
      respiratory samples nor in amoebae-containing water samples, indicating that this
      particular type of virus is either not abundant or does not contribute to
      paediatric respiratory illnesses.

PMID- 17036152
TI  - Evaluation of Rapid U Legionella Plus Test, a new immunochromatographic assay for
      detection of Legionella pneumophila serogroup 1 antigen in urine.

PMID- 17036154
TI  - MR arthrography in calcific tendinitis of the shoulder: diagnostic performance
      and pitfalls.
AB  - The purpose was to assess the diagnostic performance of MR arthrography to
      diagnose calcific tendinitis of the shoulder and to assess the reasons for
      diagnostic errors. Standard MR arthrograms of 22 patients with calcific
      tendinitis and 61 controls were retrospectively analyzed by two independent and
      blinded radiologists. All cases were consecutively collected from a database.
      Conventional radiographs were available in all cases serving as gold standard.
      The supraspinatus was involved in 16, the infraspinatus in four and the
      subscapularis in two patients. All diagnostic errors were analyzed by two
      additional readers. Reader 1 correctly detected 12 of the 22 shoulders with and
      42 of the 61 shoulders without calcific tendinitis (sensitivity 0.55, specificity
      0.66). The corresponding values for reader 2 were 13 of 22 and 40 of 61 cases
      (sensitivity 0.59, specificity 0.69). Inter-rater agreement (kappa-value) was
      0.42. Small size of the calcific deposits and isointensity compared to the
      surrounding tissue were the most important reasons for false negative results.
      Normal hypointense areas within the supraspinatus tendon substance and attachment
      were the main reason for false positive results. In conclusion, MR arthrography
      is insufficient in the diagnosis of calcific tendinitis. Normal hypointense parts
      of the rotator cuff may mimic calcific deposits and calcifications may not be
      detected when they are isointense compared to the rotator cuff. Therefore, MR
      imaging should not be interpreted without corresponding radiographs.

PMID- 17036153
TI  - Comparison of fMRI coregistration results between human experts and software
      solutions in patients and healthy subjects.
AB  - Functional magnetic resonance imaging (fMRI) performed by echo-planar imaging
      (EPI) is often highly distorted, and it is therefore necessary to coregister the
      functional to undistorted anatomical images, especially for clinical
      applications. This pilot study provides an evaluation of human and automatic
      coregistration results in the human motor cortex of normal and pathological
      brains. Ten healthy right-handed subjects and ten right-handed patients performed
      simple right hand movements during fMRI. A reference point chosen at a
      characteristic anatomical location within the fMRI sensorimotor activations was
      transferred to the high resolution anatomical MRI images by three human fMRI
      experts and by three automatic coregistration programs. The 3D distance between
      the median localizations of experts and programs was calculated and compared
      between patients and healthy subjects. Results show that fMRI localization on
      anatomical images was better with the experts than software in 70% of the cases
      and that software performance was worse for patients than healthy subjects
      (unpaired t-test: P = 0.040). With 45.6 mm the maximum disagreement between
      experts and software was quite large. The inter-rater consistency was better for
      the fMRI experts compared to the coregistration programs (ANOVA: P = 0.003). We
      conclude that results of automatic coregistration should be evaluated carefully,
      especially in case of clinical application.

PMID- 17036155
TI  - Intradiscal corticosteroid injections in spondylotic cervical radiculopathy.
AB  - The purpose of this study was to evaluate treatment outcomes with intradiscal
      injection of corticosteroids (IDIC) in cervical spondylotic radiculopathy. Twenty
      consecutive patients were treated with intradiscal injection of 25 mg of acetate
      of prednisolone under fluoroscopic control. All patients had previously received
      a nonsurgical treatment for at least 3 months without success. Outcomes were
      assessed 1, 3 and 6 months after IDIC. Radicular pain reduction as scored on a
      visual analogue scale (VAS 100-mm length) was statistically significant at 1
      month (19.0+/-28.0 mm; p=0.008), 3 months (25.2+/-27.5 mm; p=0.002), and 6 months
      (24.6+/-28.4 mm; p=0.001). In all, 40% of treated patients described at least 50%
      pain improvement 6 months after treatment. Four patients had complete relief of
      radicular pain. In conclusion, IDIC should be an alternative in the nonsurgical
      management of cervical spondylotic radiculopathy.

PMID- 17036156
TI  - Assessment of colonic transit time using MRI: a feasibility study.
AB  - The aim of this pilot study was to evaluate a new, non-invasive examination
      method using MRI for the quantification of the colonic transit time after oral
      administration of gadolinium-saline solution filled capsules. Healthy volunteers
      without previous or acute symptoms of gastrointestinal disorders were enrolled.
      After a 3-day diet for the standardization of gastrocolonic content the
      volunteers swallowed five Gd-DTPA/saline 0.9%-filled capsules. Seven different
      concentrations of Gd-DTPA/saline 0.9% solution between 1:0 and 0:1 were tested in
      a dilution series. Following ingestion of capsules, coronal Flash T1 and True
      Fisp sequences using a 1.5 Tesla system were obtained at 0 h, 3 h, 6 h, 12 h, 24
      h, 36 h and 60 h. Sequences were analyzed by two independent experts for locating
      the capsules. Overall colonic transit time was separately analyzed for both
      genders. Fifteen healthy volunteers (7 females, 8 males; mean age 34+/-13 years)
      were enrolled. The phantom study provided the best contrast in both the T1-and T2
      weighted sequences defining a ratio of 1:10 for Gd-DTPA/saline 0.9% solution. The
      mean transit time accounted for 41+/-9 h in women and for 31+/-10 h in men. MRI
      is an adequate method for the assessment of colonic transit time offering the
      advantages of no exposure to radiation, short examination time, possible dynamic
      evaluation of the transit and the practicability in terms of a future adoption to
      clinical routine.

PMID- 17036157
TI  - mini-PAT (Peer Assessment Tool): a valid component of a national assessment
      programme in the UK?
AB  - PURPOSE: To design, implement and evaluate a multisource feedback instrument to
      assess Foundation trainees across the UK. METHODS: mini-PAT (Peer Assessment
      Tool) was modified from SPRAT (Sheffield Peer Review Assessment Tool), an
      established multisource feedback (360 degrees ) instrument to assess more senior
      doctors, as part of a blueprinting exercise of instruments suitable for
      assessment in Foundation programmes (first 2 years postgraduation). mini-PAT's
      content validity was assured by a mapping exercise against the Foundation
      Curriculum. Trainees' clinical performance was then assessed using 16 questions
      rated against a six-point scale on two occasions in the pilot period. Responses
      were analysed to determine internal structure, potential sources of bias and
      measurement characteristics. RESULTS: Six hundred and ninety-three mini-PAT
      assessments were undertaken for 553 trainees across 12 Deaneries in England,
      Wales and Northern Ireland. Two hundred and nineteen trainees were F1s or PRHOs
      and 334 were F2s. Trainees identified 5544 assessors of whom 67% responded. The
      mean score for F2 trainees was 4.61 (SD = 0.43) and for F1s was 4.44 (SD = 0.56).
      An independent t test showed that the mean scores of these 2 groups were
      significantly different (t = -4.59, df 390, p < 0.001). 43 F1s (19.6%) and 19 F2s
      (5.6%) were assessed as being below expectations for F2 completion. The factor
      analysis produced 2 main factors, one concerned clinical performance, the other
      humanistic qualities. Seventy-four percent of F2 trainees could have been
      assessed by as few as 8 assessors (95% CI +/-0.6) as they either scored an
      overall mean of 4.4 or above or 3.6 and below. Fifty-three percent of F1 trainees
      could have been assessed by as few as 8 assessors (95% CI +/-0.5) as they scored
      an overall mean of 4.5 or above or 3.5 and below. The hierarchical regression
      when controlling for the grade of trainee showed that bias related to the length
      of the working relationship, occupation of the assessor and the working
      environment explained 7% of the variation in mean scores when controlling for the
      year of the Foundation Programme (R squared change = 0.06, F change = 8.5,
      significant F change <0.001). CONCLUSIONS: As part of an assessment programme,
      mini-PAT appears to provide a valid way of collating colleague opinions to help
      reliably assess Foundation trainees.

PMID- 17036158
TI  - Impairment of flow mediated vasodilatation of brachial artery in patients with
      primary hyperparathyroidism.
AB  - BACKGROUND: Hyperparathyroid condition might influence endothelial cells. The aim
      of this study was to assess flow mediated dilatation (FMD) in patients with
      primary hyperparathyroidism (PHPT). METHODS: We prospectively evaluated 21
      patients with PHPT (9 women, 12 men; aged 50 +/- 11 years, serum calcium 11.6 +/-
      0.7 mg/dl, intact parathyroid hormone (iPTH) 489 +/- 495 pg/ml) and 27 healthy
      control subjects (13 women, 14 men; aged 49 +/- 10 years, serum calcium 9.4 +/-
      0.5 mg/dl, iPTH 28 +/- 8.5 pg/ml). Endothelial function, measured as FMD of the
      brachial artery using ultrasound, was calculated in two groups. To avoid
      confounding factors, conditions known to affect endothelial function like
      diabetes mellitus, hypertension, dyslipidemia, smoking, coronary and peripheral
      artery disease were excluded from both groups. RESULTS: FMD was lower in patients
      with PHPT than that in those without (10.2 +/- 5.8 vs. 19.8 +/- 5.8, P = 0.0001).
      FMD negatively correlated with serum calcium (r = -0.55, P = 0.002). CONCLUSION:
      Endothelium-dependent FMD may impair in patients with PHPT compared to controls.
      Endothelial dysfunction can contribute to the deleterious cardiovascular effects
      of PTH excess. Therapy to reduce or retard endothelial dysfunction in patients
      with PHPT may lead to decreased cardiovascular morbidity and mortality.

PMID- 17036159
TI  - 13C-detected HN(CA)C and HMCMC experiments using a single methyl-reprotonated
      sample for unambiguous methyl resonance assignment.
AB  - Methyl groups provide an important source of structural and dynamic information
      in NMR studies of proteins and their complexes. For this purpose sequence
      specific assignments of methyl 1H and 13C resonances are required. In this paper
      we propose the use of 13C-detected 3D HN(CA)C and HMCMC experiments for
      assignment of methyl 1H and 13C resonances using a single selectively methyl
      protonated, perdeuterated and 13C/15N-labeled sample. The high resolution
      afforded in the 13C directly-detected dimension allows one to rapidly and
      unambiguously establish correlations between backbone HN strips from the 3D
      HN(CA)C spectrum and methyl group HmCm strips from the HMCMC spectrum by aligning
      all possible side-chain carbon chemical shifts and their multiplet splitting
      patterns. The applicability of these experiments for the assignment of methyl 1H
      and 13C resonances is demonstrated using the 18.6 kDa B domain of the Escherichia
      coli mannose transporter (IIBMannose).

PMID- 17036160
TI  - Sensitivity improvement for correlations involving arginine side-chain
      Nepsilon/Hepsilon resonances in multi-dimensional NMR experiments using broadband
      15N 180 degrees pulses.
AB  - Due to practical limitations in available 15N rf field strength, imperfections in
      15N 180 degrees pulses arising from off-resonance effects can result in
      significant sensitivity loss, even if the chemical shift offset is relatively
      small. Indeed, in multi-dimensional NMR experiments optimized for protein
      backbone amide groups, cross-peaks arising from the Arg guanidino 15Nepsilon
      (approximately 85 ppm) are highly attenuated by the presence of multiple INEPT
      transfer steps. To improve the sensitivity for correlations involving Arg
      Nepsilon-Hepsilon groups, we have incorporated 15N broadband 180 degrees pulses
      into 3D 15N-separated NOE-HSQC and HNCACB experiments. Two 15N-WURST pulses
      incorporated at the INEPT transfer steps of the 3D 15N-separated NOE-HSQC pulse
      sequence resulted in a approximately 1.5-fold increase in sensitivity for the Arg
      Nepsilon-Hepsilon signals at 800 MHz. For the 3D HNCACB experiment, five 15N
      Abramovich-Vega pulses were incorporated for broadband inversion and refocusing,
      and the sensitivity of Arg1Hepsilon-15Nepsilon-13Cgamma/13Cdelta correlation
      peaks was enhanced by a factor of approximately 1.7 at 500 MHz. These experiments
      eliminate the necessity for additional experiments to assign Arg 1Hepsilon and
      15Nepsilon resonances. In addition, the increased sensitivity afforded for the
      detection of NOE cross-peaks involving correlations with the 15Nepsilon/1Hepsilon
      of Arg in 3D 15N-separated NOE experiments should prove to be very useful for
      structural analysis of interactions involving Arg side-chains.

PMID- 17036161
TI  - Backbone assignment of the 98 kDa homotrimeric yeast PCNA ring.

PMID- 17036162
TI  - NMR assignment of 1H, 13C and 15N resonances of the truncated Escherichia coli
      RcsC (700-949), including the phosphoreceiver domain.

PMID- 17036163
TI  - High expression of APOBEC3G in patients infected with hepatitis C virus.
AB  - APOBEC3G (an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G;
      also known as CEM15), a member of the APOBEC family, which possesses cytidine
      deaminase activity that causes C/G to T/A transition mutations in virus genomes
      such as human immunodeficiency virus 1 and hepatitis B virus, is reported to play
      an important role in host-defense mechanisms. However, APOBEC3G expression in
      patients infected with chronic hepatitis C virus (HCV), of which there are
      currently more than 170 million worldwide, has not yet been well studied. We
      investigated this issue herein, and demonstrated an increased expression of
      APOBEC3G in both hepatocytes and lymphocytes of chronic hepatitis patients
      infected with HCV. Transfection of the NS5A gene, but not any other non
      structural protein genes of HCV tested, to the hepatocellular carcinoma cell line
      enhanced APOBEC3G expression. Incubation of the cells with interferon also
      resulted in the augmentation. These results may provide new insight into the
      pathogenesis of chronic HCV infection.

PMID- 17036164
TI  - Brain-type creatine kinase BB-CK interacts with the Golgi Matrix Protein GM130 in
      early prophase.
AB  - Creatine kinase (CK) isoenzymes are essential for storing, buffering and
      intracellular transport of "energy-rich" phosphate compounds in tissues with
      fluctuating high energy demand such as muscle, brain and other tissues and cells
      where CK is expressed. In brain and many non-muscle cells, ubiquitous cytosolic
      "brain-type" BB-CK and ubiquitous mitochondrial CK (uMtCK) act as components of a
      phosphocreatine shuttle to maintain cellular energy pools and distribute energy
      flux. To date, still relatively little is known about direct coupling of
      functional dimeric BB-CK with other partner proteins or enzymes that are
      important for cell function. Using a global yeast two-hybrid (Y2H) screen with
      monomeric B-CK as bait and a representative brain cDNA library to search for
      interaction partners of B-CK with proteins of the brain, we repeatedly identified
      the cis-Golgi Matrix protein (GM130) as recurrent interacting partner of B-CK.
      Since HeLa cells also express both BB-CK and GM130, we subsequently used this
      cellular model system to verify and characterize the BB-CK-GM130 complex by GST
      pulldown experiments, as well as by in vivo co-localization studies with confocal
      microscopy. Using dividing HeLa cells, we report here for the first time that
      GM130 and BB-CK co-localize specifically in a transient fashion during early
      prophase of mitosis, when GM130 plays an important role in Golgi fragmentation
      that starts also at early prophase. These data may shed new light on BB-CK
      function for energy provision for Golgi-fragmentation that is initiated by cell
      signalling cascades in the early phases of mitosis.

PMID- 17036166
TI  - Pelvic prolapse and urinary incontinence in nulliparous college women in relation
      to paratrooper training.
AB  - The objective of this study was to determine whether paratrooper training is
      associated with pelvic support defects or urinary incontinence. Nulliparous women
      at The United States Military Academy were examined using the Pelvic Organ
      Prolapse Quantification System and completed a questionnaire regarding
      incontinence and exercise prior to undergoing summer military training. The exam
      and questionnaire were repeated following training. One hundred sixteen women
      completed the study (80.6%), 37 of whom had attended paratrooper training. Women
      who attended paratrooper training were significantly more likely to have stage II
      prolapse (RR=2.72, 1.37<RR<5.40; p=0.003). Additionally, women who attended
      paratrooper training were significantly more likely to have worsening in their
      pelvic support regardless of initial prolapse stage (RR=1.57, 1.12<RR<2.20;
      p=0.01). Twenty-four women complained of urinary incontinence; however, this was
      not associated with paratrooper training. The forces transmitted to the female
      pelvis during paratrooper training are significant and cause pelvic support
      defects.

PMID- 17036165
TI  - Phytocomponent p-hydroxycinnamic acid stimulates bone formation and inhibits bone
      resorption in rat femoral tissues in vitro.
AB  - The effect of cinnamic acid or its related compounds, which is present in many
      plants, on bone metabolism has not been clarified yet. The effect of cinnamic
      acid, p-hydroxycinnamic acid (HCA), ferulic acid, caffeic acid, or 3,4
      dimethoxycinnamic acid (DCA) on bone calcium content in vitro was investigated.
      Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues
      were cultured for 48,h in Dulbecco's modified Eagle's medium (high glucose, 4.5%)
      supplemented with antibiotics and bovine serum albumin. The presence of HCA (10(
      5) or 10(-4),M) caused a significant increase in calcium content in the
      diaphyseal or metaphyseal tissues. Such an effect was not observed in the
      presence of cinnamic acid or other compounds at the concentration of 10(-5) or
      10(-4),M. Alkaline phosphatase activity and deoxyribonucleic acid (DNA) content
      in the diaphyseal or metaphyseal tissues was significantly increased in the
      presence of HCA (10(-5) or 10(-4),M). The effect of HCA (10(-4),M) in increasing
      calcium content, alkaline phosphatase activity, and DNA content in the diaphyseal
      or metaphyseal tissues was completely prevented in the presence of cycloheximide
      (10(-6),M), an inhibitor of protein synthesis. Thus HCA had anabolic effects on
      bone components. The presence of parathyroid hormone (PTH; 10(-7),M), a bone
      resorbing factor, caused a significant decrease in calcium content and a
      corresponding elevation in medium glucose consumption, lactic acid production or
      tartrate-resistant acid phosphatase (TRACP) activity in the diaphyseal or
      metaphyseal tissues. These alterations were completely prevented in the presence
      of HCA (10(-5) or 10(-4),M). This study demonstrates that p-hydroxycinnamic acid
      (HCA) has stimulatory effects on bone formation and inhibitory effects on bone
      resorption in tissue culture in vitro.

PMID- 17036167
TI  - Transvaginal urethrolysis for obstruction after antiincontinence surgery.
AB  - Our objective was to determine our success in relieving bladder outlet
      obstruction (BOO) with a transvaginal urethrolysis (TVU). This was a chart review
      that included 55 patients who underwent 61 TVU procedures between 2001 and 2005.
      Twenty-three patients had at least one prior TVU. Outcomes evaluated included
      obstructive symptoms, need for catheterization, postvoid residual (PVR),
      irritative symptoms, and stress urinary incontinence (SUI). Of the 46 patients
      with obstructive voiding preoperatively, 87% were cured. Of the 47 patients with
      irritative symptoms, 45% were cured, 34% improved, and 21% were left unchanged.
      SUI, generally mild, was noted postoperatively in 16% patients. Similar success
      was seen among patients with prior procedures. Aggressive TVU is very successful
      in relieving urinary retention and improving or curing overactive bladder
      symptomatology due to iatrogenic obstruction, even when a prior urethrolysis had
      been unsuccessful. SUI is an infrequent complication.

PMID- 17036168
TI  - Spontaneous closure of vesicovaginal fistulas after bladder drainage alone:
      review of the evidence.
AB  - A vesicovaginal fistula may occur as a surgical complication, the result of
      obstructed labor, or a late manifestation of radiotherapy. Surgical treatment
      includes many routes and techniques, with a success rate reaching 100%. The
      spontaneous closure of vesicovaginal fistulae following [corrected] bladder
      drainage alone for varying periods has been reported by many. The factors
      favoring the success of this conservative method have not been well examined
      [corrected] In this investigation [corrected] all articles referring [corrected]
      to this modality were reviewed [corrected] The parameters studied included
      etiology, size, interval from [corrected] causative insult to drainage, and
      duration of drainage. The incidence of spontaneous closure of fistulae
      [corrected] after bladder drainage alone ranged between [corrected] 0 and 100%.
      Among all assessed criteria, the interval to drainage seems to have the best
      correlation with success. This finding [corrected] is most likely explained on
      the basis of the epithelialization of the fistulous tract with time, preventing
      spontaneous healing. In the view of the retrospective nature of the reviewed
      articles, the absence of a detailed classification system, and the heterogeneity
      of the treatment in question, no solid conclusion regarding management
      recommendations can be drawn.

PMID- 17036169
TI  - Quality of life in women with stress urinary incontinence.
AB  - The objective of this study was to identify clinical and demographic factors
      associated with incontinence-related quality of life (QoL) in 655 women with
      stress urinary incontinence who elected surgical treatment. The following factors
      were examined for their association with QoL as measured with the Incontinence
      Impact Questionnaire (IIQ): number of incontinence (UI) episodes/day; self
      reported type of UI symptoms (stress and urge); sexual function as measured by
      the Prolapse/Urinary Incontinence Sexual Questionnaire; symptom bother as
      measured by the Urogenital Distress Inventory; as well as other clinical and
      sociodemographic factors. A stepwise least-squares regression analysis was used
      to identify factors significantly associated with QoL. Lower QoL was related to
      the greater frequency of stress UI symptoms, increasing severity, greater symptom
      bother, prior UI surgery or treatment, and sexual dysfunction (if sexually
      active). Health and sociodemographic factors associated with lower incontinence
      related QoL included current tobacco use, younger age, lower socioeconomic
      status, and Hispanic ethnicity.

PMID- 17036170
TI  - There is a low incidence of recurrent bacteriuria in painful bladder
      syndrome/interstitial cystitis patients followed longitudinally.
AB  - The objective of this paper was to establish whether patients with confirmed
      painful bladder syndrome/interstitial cystitis (PBS/IC) presenting with symptoms
      of UTI have actual bacteriuria vs a flare of their PBS/IC symptoms. One hundred
      and six (n = 106) consecutive female patients (mean age 39.8 +/- 14 years) with
      newly diagnosed IC were identified and followed longitudinally for 24 months. At
      the initial visit and at all subsequent visits, urinary specimens were obtained
      by sterile catheterization (Bard 14Fr female) and cultured for bacteria. Eight
      patients had an initially positive urine culture, and repeat cultures 8 weeks
      after treatment were all negative. Once sterile urine was established, the
      diagnosis of PBS/IC was confirmed. A pelvic pain/urgency/frequency (PUF)
      questionnaire score was obtained from 89 patients. After the diagnosis of PBS/IC,
      all patients received multimodal treatment. Patients were instructed to present
      to the office whenever they developed symptoms of UTI, at which time a sterile
      catheter specimen was obtained and sent for culture. Greater than 10(3) colonies
      were considered positive. Patients who did not report flares were contacted to
      establish whether unreported treatments were given. Seventy-two patients (68%)
      had no UTI episodes or flares. The remaining 34 patients (32%) presented with 54
      flares, of which 44 were culture-negative and 10 were culture-positive. A single
      flare was reported by 21 patients during the 24 months, with three positive
      cultures (14.3%). Recurrent UTI symptoms (two to four flares) were seen in a
      small group (n = 13) for a total of 33 flares. Of these, seven had two flares
      each (12 negative, 2 positive), five had three flares each (12 negative, 3
      positive), and one patient had four flares (two negative, two positive).
      Therefore, within the group with recurrent symptoms, seven positive cultures were
      obtained for a rate of recurrent bacteriuria of 6.6% (7/106). Nine of the 10
      positive bacterial cultures were due to gram-negative bacteria: Escherichia coli
      (n = 6), Proteus mirabilis (n = 1), Klebsiella pneumonia (n = 1), and Citrobacter
      sp. (n = 1). One grew Streptococcus sp. There was no difference between the flare
      group and nonflares in regards to age or PUF scores between groups. This study is
      the first to report on the low incidence of confirmed UTIs in a large group of
      PBS/IC patients followed longitudinally. These data suggest that only a small
      number of PBS/IC patients with UTI symptoms have positive urine cultures (9.4%;
      10/106). Although the symptoms of recurrent UTI are prevalent in IC patients, the
      incidence of confirmed recurrent UTIs is only 6.6%. Because the flares of IC are
      usually self-limiting, treatment response to antibiotics may be misleading in
      light of the low incidence of positive urine cultures. These data suggest that
      the symptom flares of IC are not usually associated with recurrent UTI and,
      therefore, are likely due to a triggering of the other painful mechanisms
      involved in IC patients who are culture-negative.

PMID- 17036171
TI  - Leptin and bone turnover in monochorionic twins complicated by twin-twin
      transfusion syndrome.
AB  - INTRODUCTION: To test the hypothesis that the bone metabolism of a growth
      restricted foetus is regulated by genetic, placental and/or foetal factors
      through leptin, we investigated the foetal bone turnover in monochorionic
      pregnancies complicated with or without twin-twin transfusion syndrome (TTTS).
      METHODS: Maternal and cord bloods were collected from gestational-age-matched
      monochorionic twins with (n=15) and without (n=15) TTTS. The samples were assayed
      for leptin, cross-linked carboxyl terminal telo-peptide (ICTP, a marker of bone
      resorption) and pro-peptide (PICP, a marker of bone formation) of type I collagen
      by radioimmunoassay (RIA). RESULTS: In the growth-restricted donor twin, the
      plasma concentration of leptin (P < 0.001), PICP (P < 0.001) was lower, while
      that of ICTP (P < 0.001) was higher than the recipient twin of the TTTS group. In
      contrast, leptin, PICP and ICTP were comparable in non-TTTS twins. In the
      recipient twin of TTTS and non-TTTS twins, leptin was positively associated with
      PICP (r=0.73; n=45, P < 0.001) and negatively with ICTP (r=-0.68; n=45; P <
      0.001). No such association was found between leptin and bone marker in the
      growth-restricted donor twin of the TTTS group. CONCLUSION: Our data suggest
      that, in AGA twins, leptin maintains bone metabolism by inhibiting resorption and
      enhancing bone formation. In contrast, growth-restricted donor twins have high
      bone turnover and this does not seem to be due to leptin deficiency.

PMID- 17036174
TI  - Historical background of Alzheimer's research done 100 years ago.

PMID- 17036173
TI  - Effects of spinal cord injury on osteoblastogenesis, osteoclastogenesis and gene
      expression profiling in osteoblasts in young rats.
AB  - INTRODUCTION: Spinal cord injury (SCI) causes a significant amount of bone loss
      in the sublesional area in animals and humans, and this type of bone loss is
      different from other forms of osteoporosis such as disuse osteoporosis and
      postmenopausal osteoporosis. However, no data is available on the cellular and
      molecular changes of osteoblastogenesis and osteoclastogenesis during SCI-induced
      bone loss. METHODS: SCI and SHAM rats were used in this study to investigate
      osteoblastogenesis and osteoclastogenesis in bone-marrow culture. We also
      measured bone mass and bone histomorphometry, as well as the expression of
      alkaline phosphatase (ALP), core binding factor alpha1 (Cbfa-1), osterix,
      receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in
      osteoblast-like cells in bone-marrow culture obtained from SCI and SHAM rats.
      RESULTS: Bone mineral density (BMD) measurement showed serious bone loss in the
      tibial ephiphyses and metaphyses of SCI rats compared with SHAM rats. In
      addition, bone histomorphometry analysis of the tibial metaphyses of SCI rats
      demonstrated that bone microarchitecture in SCI rats deteriorated further than in
      SHAM rats, and increased eroded surfaces and bone formation rates were observed
      in SCI rats. The number of osteoclasts that developed from bone marrow of SCI
      rats at equal density was significantly increased compared with SHAM rats, and
      the area of the resorption pits formed in the bone marrow culture from SCI rats
      was significantly greater than SHAM rats, whereas the number of CFU-F and CFU-OB
      was similar in both groups. RANKL mRNA and protein levels in osteoblast-like
      cells in culture obtained from SCI rats were significantly higher than those from
      the SHAM rats, whereas OPG levels decreased slightly. The ratios of RANKL to OPG
      expression in SCI rats were significantly higher than those in SHAM rats.
      However, osteogenic gene profiling of Cbfa-1, ALP and osterix in SCI rats
      remained similar with SHAM rats. CONCLUSION: These changes favor increased
      osteoclast activity over osteoblast activity, and may explain, in part, the
      imbalance in bone formation and resorption following SCI.

PMID- 17036175
TI  - The significance of neuroinflammation in understanding Alzheimer's disease.
AB  - The interest of scientists in the involvement of inflammation-related mechanisms
      in the pathogenesis of Alzheimer's disease (AD) goes back to the work of one of
      the pioneers of the study of this disease. About hundred years ago Oskar Fischer
      stated that the crucial step in the plaque formation is the extracellular
      deposition of a foreign substance that provokes an inflammatory reaction followed
      by a regenerative response of the surrounding nerve fibers. Eighty years later
      immunohistochemical studies revealed that amyloid plaques are indeed co-localized
      with a broad variety of inflammation-related proteins (complement factors, acute
      phase proteins, pro-inflammatory cytokines) and clusters of activated microglia.
      These findings have led to the view that the amyloid plaque is the nidus of a non
      immune mediated chronic inflammatory response locally induced by fibrillar A beta
      deposits. Recent neuropathological studies show a close relationship between
      fibrillar A beta deposits, inflammation and neuroregeneration in relatively early
      stages of AD pathology preceding late AD stages characterized by extensive tau
      related neurofibrillary changes. In the present work we will review the role of
      inflammation in the early stage of AD pathology and particularly the role of
      inflammation in A beta metabolism and deposition. We also discuss the
      possibilities of inflammation-based therapeutic strategies in AD.

PMID- 17036178
TI  - [Heart and sports].

PMID- 17036177
TI  - Treatment of postural tachycardia syndrome: a comparison of octreotide and
      midodrine.
AB  - We assessed the potency of octreotide and midodrine, and their combination, in
      the treatment of the postural tachycardia syndrome (POTS) and orthostatic
      intolerance (OI). Nine patients with POTS and six patients with OI stood for up
      to 1 hour while their HR and BP were monitored. Patients received on separate
      days, midodrine 10 mg 1 hour before testing, octreotide 0.9 micro g/kg 8 minutes
      before testing or combination therapy. Standing time in the patients with POTS
      was 41.2 +/- 8.4 minutes and not improved by midodrine or octreotide, but
      increased to 56.3 +/- 2.7 (P < 0.01) minutes following combination therapy. The
      standing heart rate in POTS, 114 +/- 0.7 bpm, was suppressed by midodrine 92.8 +/
      0.7 (P < 0.001), octreotide 90.6 +/- 0.78 (P < 0.001), and combination therapy
      84.7 +/- 0.7 (P < 0.001). Combination therapy was better than monotherapy (P <
      0.001) but only for the first 10 minutes of standing. Standing time of 36.3 +/-
      3.5 minutes in the patients with OI improved with midodrine, octreotide and
      combination therapy (55.5 +/- 3.1, 56.5 +/- 3.5, and 56.6 +/- 3.3, respectively,
      P < 0.05 for each). Standing heart rate in OI was 100 +/- .76 bpm; following
      midodrine it was 80.3 +/- .69 (P < 0.05), following octreotide it was 84.8 +/-
      .86, and following combination therapy it was 71.2 +/- .9 (P < 0.01). The RR
      interval versus time area under the curve (The Orthostatic Index) was 21.1 +/- 4
      in patients with OI. After midodrine it was 41.4 +/- 3.5 (P < 0.01), after
      octreotide 40.3 +/- 3.8 (P < 0.01) and after the combination it was 47.3 +/- 4.6
      (P < 0.001). Midodrine and octreotide suppressed tachycardia in POTS and improved
      standing times in OI. The two drugs had similar potencies; combination therapy
      was not significantly better than monotherapy.

PMID- 17036179
TI  - [Heart and sports medicine-history and perspectives].
AB  - The origin of sports medicine in the 19th and 20th century is listed. The same
      applies to the development of devices in the course of performance diagnostics.
      The required parameters for evaluation of the cardiopulmonary performance ability
      are mentioned in their historical context.The athlete's heart is described from
      its beginnings until today in its differently characterized clinical concepts.
      The secured facts are provided in detail in combination with modern investigation
      techniques.A particular sports medical merit in the area of cardiology is the
      investigation of the significance of the body periphery regarding the heart
      activity. The performance-limiting factors for the local aerobic dynamic
      endurance are specified in addition to the training methods for performance
      enhancement and the consequences for heart activity. The paper closes with a
      short description of the significance of sports medicine for today's
      rehabilitative cardiology.

PMID- 17036180
TI  - [Overweight and obesity in childhood and adolescence. Is prevention possible?].
AB  - The prevalence of overweight and obesity in children and adolescents is
      increasing. In Germany, 10-20% of children and youth are overweight and obese.
      Childhood obesity is associated with cardiovascular and other comorbidities. 25%
      suffer from arterial hypertension and/or hypercholesterolemia, 1% from diabetes
      mellitus type 2. In addition, one third suffer from orthopedic and psychosocial
      disorders.Therefore, countermeasures are necessary. Kindergarten or school
      settings offer a possibility for preventive measures. Results, however, are
      inconsistent and depend on several factors such as socioeconomic status, parental
      integration, etc. To counteract the epidemic of obesity, national and
      international data should be collected, results and recommendations adapted to
      individual necessities of different settings. The implementation of such
      strategies is only possible with a combined and qualified procedure by a
      concerted and qualified action of all health care employees based on adequate
      political structures.

PMID- 17036181
TI  - [Cardiovascular preparticipation screening of competitive athletes].
AB  - Cardiovascular deaths during or following sport activities repeatedly raise the
      question about a practicable preparticipation screening for athletes to prevent
      such adverse events. In Germany and most European countries, well-equipped sports
      medicine centers evaluate the health of the Olympic athletes through regular
      checkups, which include a detailed medical history and thorough physical
      examination as well as an ECG at rest, a stress ECG, and an echocardiography. In
      professional sports, guidelines for this screening differ according to the
      federations, however, most of them intend to follow the recommendations of the
      Olympic sports system. For nonprofessional competitive sports, there are no
      guidelines for preparticipation screening, although these athletes train at the
      same level of intensity as professional athletes. The main issue in this
      international debate is the question of cost-effectiveness and how to finance
      preventive measures.

PMID- 17036182
TI  - [Physical activity and prevention of cardiovascular diseases].
AB  - Physical inactivity is one of the major risk factors for cardiovascular diseases.
      Regular physical activity, conversely, is effective in reducing all-cause
      mortality, cardiovascular morbidity and mortality. Older and recent meta-analyses
      confirm the reduction of all-cause mortality and cardiovascular mortality by
      regular physical activity. So far, there is a dose-effect relationship especially
      from low to moderate training intensity; the steepness of this curve is more
      curvilinear with a decrease at higher categories of activity intensity. Regular
      physical activity even at low level of intensity should be a part of daily life
      and of lifestyle. The risks and side effects of physical activity can be
      neglected, preparticipation examination before training is strongly recommended.
      Counseling healthy persons and patients at any age for physical activity, and
      training prescription should be an essential part of physicians' work in general
      practice.

PMID- 17036183
TI  - [Exercise in arterial hypertension].
AB  - Regular endurance training has established itself as a major therapeutic
      principle in the specter of nonpharmacological measures in arterial hypertension.
      An initial medical check as well as an adequate technique, dosage and intensity
      of the prescribed exercise training are mandatory. With respect to the
      concomitant pharmacological treatment, it should be considered that the
      beneficial effects of lifestyle modification will not be counteracted by the
      chosen antihypertensive drug but, ideally, synergistically supported. Based on
      the individual clinical situation, principally all antihypertensive drugs
      recommended by the current European guidelines, may be prescribed as mono- or
      combination therapy.beta-receptor blockers are especially capable of controlling
      excessive exercise-induced blood pressure increase; however, they have metabolic
      and exercise physiological limitations. The neutrality concerning metabolic and
      exercise physiological parameters as well as the positive profile of side effects
      favor ACE inhibitors, long-acting calcium channel blockers and especially AT(1)
      antagonists in physically active hypertensive patients with concomitant metabolic
      syndrome.

PMID- 17036184
TI  - Sports-specific features of athlete's heart and their relation to
      echocardiographic parameters.
AB  - Chronic physical training may induce morphological and useful functional
      adaptations which affect all cardiac chambers. Morphological modifications are
      mainly modest and far from pathologic ones. All these adaptations seem helpful
      for sport's performance. Hemodynamic and neurohumoral stresses depend on the
      muscular exercise type performed, static or dynamic. However, sports-specific
      adaptive cardiac structural changes are yet debated. Actually, it appears that
      highly trained athletes develop a left ventricular fair combination of cavity
      dilatation and increased wall thickness. Thus, it is not possible to clearly
      separate a strength-trained from an endurance-trained athlete's heart. However,
      this review shows that some specific cardiac adaptations mainly linked to the
      specific training stimulus may be observed. Dilatation slightly predominates in
      dynamic endurance-trained athletes whereas increased wall thickness slightly
      predominates in dynamic resistance- and static-trained athletes. Thus, assessment
      of athletes' echocardiographic parameters should take into account both sport and
      training specificities practiced, in terms of quantity and contents.

PMID- 17036185
TI  - [Heart rate variability and physical exercise. Current status].
AB  - Heart rate variability (HRV) has long been used in risk stratification for sudden
      cardiac death and diabetic autonomic neuropathy. In recent years, both time and
      frequency domain indices of HRV also gained increasing interest in sports and
      training sciences. In these fields, HRV is currently used for the noninvasive
      assessment of autonomic changes associated with short-term and long-term
      endurance exercise training in both leisure sports activity and high-performance
      training. Furthermore, HRV is being investigated as a diagnostic marker of
      overreaching and overtraining.A large body of evidence shows that, in healthy
      subjects and cardiovascular patients of all ages (up to an age of 70 years),
      regular aerobic training usually results in a significant improvement of overall
      as well as instantaneous HRV. These changes, which are accompanied by significant
      reductions in heart rates both at rest and during submaximal exercise, reflect an
      increase in autonomic efferent activity and a shift in favor of enhanced vagal
      modulation of the cardiac rhythm. Regular aerobic training of moderate volume and
      intensity over a minimum period of 3 months seems to be necessary to ensure these
      effects, which might be associated with a prognostic benefit regarding overall
      mortality.At present, available data does not allow for final conclusions with
      respect to the usefulness of traditional HRV indices in assessing an individual's
      exercise performance and monitoring training load. The discrepant results
      published so far are due to several factors including insufficient study size and
      design, and different HRV methods. Large-sized and prospectively designed studies
      are necessary for clarification. It also remains to be seen, whether the
      traditional HRV indices prove useful in the diagnosis of overreaching and
      overtraining. Preliminary results, though promising, need to be confirmed in
      larger cohorts.A basic problem in HRV analysis is nonstationarity of the heart
      rate signal, which holds particularly true for exercise conditions. Whether, in
      these conditions, more robust nonlinear HRV methods offer a benefit has to be
      established in further work.

PMID- 17036186
TI  - Exercise and the risk of sudden cardiac death.
AB  - Sports activity may precipitate acute fatalities in both adults and young
      competitive athletes with concealed heart diseases. However, the risk-benefit
      ratio of physical exercise differs among these two age groups. In adolescents and
      young adults, competitive physical exercise is associated with a significant
      increase of the risk of sudden death. Sports is not "per se" cause of the
      enhanced mortality in this age group; rather, it acts as a trigger of cardiac
      arrest in those athletes who are affected by silent cardiovascular conditions,
      mostly cardiomyopathy, premature coronary artery disease and congenital coronary
      anomalies, which predispose to life-threatening ventricular arrhythmias during
      physical exercise. In adults, on the other hand, physical activity can be
      regarded as a "two-edged sword": vigorous exertion increases the incidence of
      acute coronary events in individuals who did not exercise regularly, whereas
      habitual physical activity reduces the overall risk of myocardial infarction and
      sudden coronary death by preventing development of coronary artery disease and
      progression of coronary atherosclerotic lesions.

PMID- 17036187
TI  - [Heart groups in Germany-current situation and prospects].
AB  - Currently, more than 6,600 heart groups (AHGs) have been established in Germany,
      in which more than 110,000 patients are physically active. Following cardiac
      rehabilitation (CR) after an acute event, in the AHG patients aim to meet the set
      rehabilitation goals in groups of about 15-20 patients, instructed by a competent
      exercise therapist and attended by a physician. While physical activity has been
      the dominant aspect thus far, psychosocial and educative elements are now more
      strongly integrated to stabilize secondary prevention. According to the German
      rehabilitation law, the patient is legally entitled to participate in AHGs. The
      insurance companies pay 6.00 Euros for 90 therapeutic units at 60-90 min each.
      Thereafter, the patient should be encouraged to continue participation at his/her
      own cost. The opportunity to participate in AHG is not yet sufficiently responded
      to by the patients. According to different studies, only 13-40% of all patients
      attend an AHG after phase II CR. In future, special emphasis has to be placed on
      the recruitment of more patients into AHGs, especially those groups which are
      known to be underrepresented (e. g., women, old patients, patients with low
      socioeconomic status). Furthermore, AHGs have to be established for patients with
      special needs, e. g., heart failure patients or young grown-ups with congenital
      heart diseases. Until now, the efficiency of AHG participation has not been
      sufficiently investigated. In a case-control study analyzing the long-term
      results of AHG participation, an improvement in physical performance as well as a
      reduction of cardiovascular morbidity (54%) and medical costs (approximately 47%)
      were observed. In future, more high-class investigations on this field are
      needed.

PMID- 17036188
TI  - [Cardiovascular side effects of anabolic-androgenic steroids].
AB  - The intake of anabolic-androgenic steroids (AAS) leads to an increase in skeletal
      muscle mass and is prohibited as a doping measure in sport. AAS abuse is not
      limited to competitive athletes. It is also prevalent in subjects who do body
      building or resistance training for cosmetic reasons only. Out of the numerous
      and partly serious side effects, the cardiovascular ones are presented here. An
      increase in left ventricular muscle mass is well documented, and some researchers
      have even reported concentric hypertrophy. By contrast, resistance training
      without AAS intake does not lead to increased ventricular wall thickness. AAS do
      not affect the systolic function of the left ventricle, whereas diastolic
      function might be impaired. Different ultrastructural myocardial alterations have
      been documented in animal studies. In addition, AAS can induce arterial
      hypertension. Blood clotting and fibrinolysis are negatively affected, and
      several case studies of thrombi exist in young strength athletes. Changes in the
      concentration of blood lipoproteins, particularly a reduction in vessel
      protective HDL cholesterol, can lead to early atherosclerosis. Many case reports
      exist about cardiac deaths in seemingly healthy subjects-most often body builders
      and other strength athletes. In fatal and nonfatal myocardial infarctions patent
      coronary arteries were proven frequently. Besides the prothrombotic effects of
      AAS, an impaired endothelial function and vasospasms are discussed hypothetically
      as pathomechanisms. Also, cardiomyopathies can occur due to AAS abuse. On the
      basis of the described possible cardiovascular side effects, it can be concluded
      that in cases of sudden cardiac deaths in young athletes, a misuse of AS should
      be excluded.

PMID- 17036189
TI  - Coronary atherosclerosis and cardiovascular risk in masters male marathon
      runners. Rationale and design of the "marathon study".
AB  - BACKGROUND: Regular physical exercise is recommended to reduce cardiovascular
      mortality. And yet, atherosclerosis is the main cause of exercise-associated
      death in persons beyond age 35. The need for risk stratification in marathon
      runners is under discussion. The predictive value of modern imaging- and non
      imaging-based markers of risk that can be used for risk stratification in masters
      endurance athletes still deserves exploration. METHODS: Male runners > 50 years
      who have completed at least five marathon races during the preceding 3 years and
      do not suffer from coronary artery disease, angina nor diabetes mellitus are
      studied to assess the predictive value of established and modern imaging- based
      and biochemical cardiovascular risk factors. Laboratory parameters including
      clinical chemistry, hematology and hormone measurements are determined. Lifestyle
      related risk factors, psychosocial and socioeconomic variables are explored using
      standardized questionnaires. Coronary, carotid, femoral and aortic
      atherosclerosis is measured using electronbeam computed tomography and
      ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate
      variability are performed. Myocardial morphology and function are assessed using
      echocardiography and magnetic resonance imaging. Participants are invited to
      compete in a marathon race to quantify the association of coronary
      atherosclerosis with marathon-related changes of cardiac troponin levels and the
      extent of marathon-induced inflammation. At the cellular level, the effect on the
      amount of circulating progenitor cells (EPCs) is determined by FACS analysis.
      Changes in laboratory parameters and hormone levels are also studied. Annual long
      term follow-up including hospital records and death certificates is performed.
      Data are compared with those from a general unselected cohort from the Heinz
      Nixdorf Recall Study. CONCLUSION: This study should contribute to cardiovascular
      risk assessment in the growing number of masters marathon runners with a focus on
      assessing the predictive value of modern imaging techniques and biochemical
      markers for comprehensive risk stratification.

PMID- 17036190
TI  - [Ironman and cardiac transplantation. High sporting exercise capacity before and
      after cardiac transplantation].
AB  - The case of a 45-year-old man is reported who was an active competitive sportsman
      up to his 38th year. In fall of 1998, exercise limitation was noted. The
      cardiologic work-up revealed dilated cardiomyopathy. In spite of intensive
      medical therapy clinical course deteriorated within the next 3 years, cardiologic
      findings and a follow-up in CPET (cardiopulmonary exercise testing) showed a
      rapid decline. In May 2002, he was listed for cardiac transplantation. In August
      2003, an orthotopic bicaval cardiac transplantation was performed at the
      University of Gottingen, Germany. The patient was followed regularly in the
      office. Physical exercise capacity increased significantly and he was able to
      participate in the 10-km New Year's run of 2003. Since 2004, he has been working
      very successfully as a coach for competitive swimmers. Based on CPET findings,
      actual views and concepts regarding the pathophysiology and training of chronic
      heart failure are discussed and the question is raised whether and in which
      respect a sportive predisposition favors the clinical outcome.

PMID- 17036191
TI  - Pneumopericardium followed by pericardial effusion after thoracic trauma and
      pacemaker implantation.

PMID- 17036192
TI  - [Postconditioning: a brief review].
AB  - Preconditioning is the most effective form of cardioprotection that can be
      induced via different interventions before a longer-lasting ischemia (= index
      ischemia). Preconditioning can be induced by short bouts of ischemia, several
      pharmaceuticals (e.g., adenosine), and volatile anesthetics. A brief ischemia of
      an organ other than the heart can likewise initiate protection of the heart,
      which has been called preconditioning at a distance or remote preconditioning.
      According to the more recent literature, short bouts of ischemia after an index
      ischemia can also initiate cardioprotection, e.g., improve postischemic
      dysfunction or reduce infarct size, which has been called postconditioning. Such
      a postconditioning can also be elicited at a distant organ, termed remote
      postconditioning. It is the aim of this short review to characterize
      preconditioning and in particular postconditioning, describe possible mechanisms,
      and call attention to the clinical relevance.

PMID- 17036193
TI  - Guest editorial. Special issue on neuroendocrine tumors.

PMID- 17036194
TI  - Functional imaging of neuroendocrine tumours with PET.
AB  - Several pathophysiological attributes of neuroendocrine tumours (NET) can be
      addressed by specific radiolabelled probes. This paper provides an overview on
      the different radiopharmaceuticals that have been developed for Positron Emission
      Tomography (PET) of neuroendocrine tumours. A review of the literature on 18F
      fluordeoxyglucose (FDG), biogenic amine precursors, somatostatin analogues and
      hormone syntheses markers is presented. Due to the highly specific tracers that
      lack any clear anatomical landmarking the advantages of integrated PET/CT are
      obvious. Amine precursors should be employed in most gastroenteropancreatic NET,
      FDG should be preserved for more aggressive, less differentiated NETs.
      Somatostatin analogues are the most promising tracers, since they can improve
      dosimetry in cases in which radiopeptide therapies are planned. In conclusion,
      the individual diagnostic approach using PET or the integrated PET/CT should be
      tailored depending on the histological classification and the differentiation of
      the tumour.

PMID- 17036195
TI  - Neuroendocrine tumors secreting growth hormone-releasing   hormone:
      Pathophysiological and clinical aspects.
AB  - Hypothalamic GHRH is secreted into the portal system, binds to specific surface
      receptors of the somatotroph cell and elicits intracellular signals that modulate
      pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and
      expressed in multiple extrapituitary tissues. Excessive peripheral production of
      GHRH by a tumor source would therefore be expected to cause somatotroph cell
      hyperstimulation, increased GH secretion and eventually pituitary acromegaly.
      Immunoreactive GHRH is present in several tumors, including carcinoid tumors,
      pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal
      adenomas, and pheochromocytomas which have been reported to secrete GHRH.
      Acromegaly in these patients, however, is uncommon. The distinction of pituitary
      vs. extrapituitary acromegaly is extremely important in planning effective
      management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH
      levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of
      acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic
      patients with pituitary tumors from those harbouring extrapituitary tumors.
      Plasma GHRH levels are usually elevated in patients with peripheral GHRH
      secreting tumors, and are normal or low in patients with pituitary acromegaly.
      Unique and unexpected clinical features in an acromegalic patient, including
      respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones
      sometimes are helpful in alerting the physician to diagnosing non pituitary
      endocrine tumors. If no facility to measure plasma GHRH is available, and in the
      absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and
      abdominal ultrasound could be performed to exclude with good approximation the
      possibility of an ectopic GHRH syndrome. Surgical resection of the tumor
      secreting ectopic GHRH should be the logical approach to a patient with ectopic
      GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors
      is generally unsuccessful in controlling the activated GH axis. Somatostatin
      analogs provide an effective option for medical management of carcinoid patients,
      especially those with recurrent disease. In fact, long-acting somatostatin
      analogs may be able to control not only the ectopic hormonal secretion syndrome,
      but also, in some instances, tumor growth. Therefore, although cytotoxic
      chemotherapy, pituitary surgery, or irradiation still remain available
      therapeutic options, long-acting somatostatin analogs are now preferred as a
      second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.

PMID- 17036196
TI  - PRKAR1A mutations in primary pigmented nodular adrenocortical disease.
AB  - Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare primary
      bilateral adrenal defect causing corticotropin-independent Cushing's syndrome. It
      occurs mainly in children and young adults. Macroscopic appearance of the
      adrenals is characteristic with small pigmented micronodules observed in the
      cortex. PPNAD is most often diagnosed in patients with Carney complex (CNC), but
      it can also be observed in patients without other manifestations or familial
      history (isolated PPNAD). The CNC is an autosomal dominant multiple neoplasia
      syndrome characterized by the association of myxoma, spotty skin pigmentation and
      endocrine overactivity. One of the putative CNC genes has been identified as the
      gene of the regulatory R1A subunit of protein kinase A (PRKAR1A), located at
      17q22-24. Germline heterozygous inactivating mutations of PRKAR1A have been
      reported in about 45% of patients with CNC, and up to 80% of CNC patients with
      Cushing's syndrome due to PPNAD. Interestingly, such inactivating germline
      PRKAR1A mutations have also been found in patients with isolated PPNAD. The hot
      spot PRKAR1A mutation termed c.709[-7-2]del6 predisposes mostly to isolated
      PPNAD, and is the first clear genotype/phenotype correlation described for this
      gene. Somatic inactivating mutations of PRKAR1A have been observed in
      macronodules of PPNAD and in sporadic cortisol secreting adrenal adenomas.
      Isolated PPNAD is a genetic heterogenous disease, and recently inactivating
      mutations of the gene of the phosphodiesterase 11A4 (PDE11A4) located at 2q31
      2q35 have been identified in patients without PRKAR1A mutations. Interestingly,
      both PRKAR1A and PDE11A gene products control the cAMP signaling pathway, which
      can be altered at various levels in endocrine tumors.

PMID- 17036198
TI  - Ceramide induces apoptosis via a peroxisome proliferator-activated receptor gamma
      dependent pathway.
AB  - Both of ceramide and PPARgamma ligand can trigger cancer cell apoptosis. We here
      show that C2-ceramide can modulate PPARgamma expression level and its
      transcriptional activity and results in apoptosis in HT29 cells. Administration
      of PPARgamma specific antagonist GW9662 partially prevents HT29 cells from
      apoptosis. Furthermore, MAP kinase pathway provided a potential modulation
      mechanism for PPARgamma pathway related with ceramide. Our results are the first
      to demonstrate that C2-ceramide induces apoptosis via a PPARgamma-dependent
      pathway.

PMID- 17036199
TI  - Involvement of both caspase-dependent and -independent pathways in apoptotic
      induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma
      cells.
AB  - Photodynamic therapy (PDT) is a cancer treatment based on the interaction of a
      photosensitizer, light and oxygen. PDT with the endogenous photosensitizer,
      protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or its
      derivatives is a modification of this treatment modality with successful
      application in dermatology. However, the mechanism of cell destruction by ALA-PDT
      has not been elucidated. In this study a human T-cell lymphoma Jurkat cell line
      was treated with PDT using hexaminolevulinate (HAL, hexylester of ALA). Four
      hours following treatment nearly 80% of the cells exhibited typical apoptotic
      features. Mitochondrial pro-apoptotic proteins were evaluated by Western blots in
      subcellular fractionated samples. PDT caused cytosolic translocation of
      cytochrome c and nuclear redistribution of apoptosis-inducing factor (AIF), but
      the release of mitochondrial Smac/DIABLO, Omi/HtrA2 and EndoG was not observed.
      The release of cytochrome c was followed by the cleavage of caspase-9 and caspase
      3 as well as its downstream substrates, together with oligonucleosomal DNA
      fragmentation. The pan-caspases inhibitor, z-VAD.fmk, prevented oligonucleosomal
      DNA fragmentation, but failed to inhibit PDT-mediated apoptosis. The apoptotic
      induction by AIF-mediated caspase-independent pathway was also found after HAL
      PDT with large-scale DNA fragmentation in the presence of z-VAD.fmk. These
      results demonstrate that cytochrome c-mediated caspase-dependent pathway and AIF
      induced caspase-independent pathway are simultaneously involved in the apoptotic
      induction by PDT. When the cytochrome c-induced caspase-dependent pathway is
      blocked, the cells go into apoptosis via AIF-mediated pathway, clearly
      demonstrating that the cytochrome c-mediated caspase-dependent pathway is not
      required for such apoptotic induction. This finding may have an impact on
      improved PDT effectiveness.

PMID- 17036197
TI  - RET and neuroendocrine tumors.
AB  - The RET proto-oncogene encodes a receptor tyrosine kinase that is a main
      component of the signaling pathway activated by the glial cell line-derived
      neurotrophic factor family ligands. Gene targeting studies revealed that
      signaling through RET plays a crucial role in neuronal and renal organogenesis.
      It is well-known that germline mutations in RET lead to the human inherited
      diseases, multiple endocrine neoplasia type 2 (MEN 2) and Hirschsprung's disease,
      and that somatic rearrangements of RET cause papillary thyroid carcinoma. Due to
      marked advances in understanding of the molecular mechanisms of the development
      of MEN 2, a consensus on MEN 2 management associated with RET status is being
      reached and currently put into general use as a guideline. In this review, we
      summarize progress in the study of RET from bench to bedside, focusing on
      pathophysiology of neuroendocrine tumors.

PMID- 17036200
TI  - Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially
      independent from action of caspases and exhibits necrosis-like features.
AB  - Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica
      that is injected into the cytosol of host cells where it targets MAP kinase
      kinases (MKKs) and inhibitor of kappaB kinase (IKK)-beta resulting in inhibition
      of cytokine production as well as induction of apoptosis in murine macrophages
      and dendritic cells (DC). Here we show that DC death was only partially prevented
      by the broad spectrum caspase inhibitor zVAD-fmk, indicating simultaneous caspase
      dependent and caspase-independent mechanisms of cell death induction by YopP.
      Microscopic analyses and measurement of cell size demonstrated necrosis-like
      morphology of caspase-independent cell death. Application of zVAD-fmk prevented
      cleavage of procaspases and Bid, decrease of the inner transmembrane
      mitochondrial potential DeltaPsi(m) and mitochondrial release of cytochrome c.
      From these data we conclude that YopP-induced activation of the mitochondrial
      death pathway is mediated upstream via caspases. In conclusion, our results
      suggest that YopP simultaneously induces caspase-dependent apoptotic and caspase
      independent necrosis-like death in DC. However, it has to be resolved if necrosis
      like DC death occurs independently from apoptotic events or as an apoptotic
      epiphenomenon.

PMID- 17036202
TI  - What is the optimal time of surgical intervention after an acute attack of
      sigmoid diverticulitis: early or late elective laparoscopic resection?
AB  - PURPOSE: This prospective study was designed to check the ideal time of surgical
      intervention by comparing the results of early elective laparoscopic sigmoid
      resection after an inflammatory attack with those of late elective resection
      during the inflammation-free interval. METHODS: A total of 210 patients (114
      males) underwent laparoscopic resection for acute sigmoid diverticulitis between
      1999 and 2005. They were prospectively divided into two groups: Group I with an
      early elective sigmoid resection (5-8 days after initial antibiotic treatment);
      Group II in the inflammation-free interval (4-6 weeks after initial
      hospitalization). RESULTS: There was no difference between the groups with regard
      to age (55.7 years), American Society of Anesthesiologists score (1.86), previous
      diseases, and extent of inflammation. After surgery, 156 patients (74.3 percent)
      were complication-free. There was a total of ten conversions (Group I, 9; Group
      II, 1; P<0.05). Minor complications developed in 42 patients (abdominal wall
      abscess=24, intestinal atony=6, hematoma=9, urinary tract infection=2). Eight
      patients in Group I (P<0.05) developed anastomotic leaks. None of the patients
      died. CONCLUSIONS: In the majority of patients, laparoscopic sigmoid resection in
      sigmoid diverticulitis can be performed without conversion. Patients who
      underwent surgery in the inflammation-free interval had a lower complication rate
      than those submitted to early elective resection. In our patient population, we
      were able to show that surgery in the inflammation-free interval significantly
      reduces postoperative morbidity. It is thus preferable for patients with sigmoid
      diverticulitis to receive initial antibiotic treatment and then undergo late
      elective laparoscopic sigmoid resection.

PMID- 17036203
TI  - The impact of surgery for colorectal cancer on quality of life and functional
      status in the elderly.
AB  - PURPOSE: Colorectal cancer is a common diagnosis in the elderly. Frequently
      concerns arise about outcomes after surgery, and little is known about
      postoperative quality of life in this older group after major bowel surgery. The
      objective of this study was to compare quality of life and functional status of
      elderly patients (older than aged 80 years) who have undergone surgery for
      colorectal cancer with a younger (younger than aged 70 years), procedure-matched
      control group. METHODS: Patients in the case (older than aged 80 years) and
      control groups (younger than aged 70 years) were identified from the colorectal
      cancer database at Mount Sinai Hospital, Toronto, Canada. All had treatment for
      colorectal cancer within the last five years. Patients were surveyed by mail
      using the European Organization for Research and Treatment of Cancer quality of
      life scales specific to cancer and colorectal cancer (EORTC-C30 and EORTC-CR38)
      and the Short Form-36. Student's t-test was used to test differences. RESULTS:
      There were 29 patients in each of the groups. The current average ages were 83.2
      (standard deviation=2.79) years, and 67.7 (standard deviation=5.1) years,
      respectively. The two groups scored similarly on the European Organization for
      Research and Treatment of Cancer quality of life scales in all domains except
      physical functioning, functional role, micturition, and stoma-related problems.
      Similarly, the mean scores of the Short Form-36 were similar with the exception
      of the vitality domain. Most patients did not require special assistance or
      alternate living arrangements after discharge from the hospital, and most
      patients seemed to be able to return to their preoperative level of functioning.
      However, stoma care was a greater concern to the elderly. CONCLUSIONS: Elderly
      patients older than aged 80 years who are selected for surgery have a quality of
      life comparable to younger patients in most respects. Therefore, colorectal
      cancer surgery may be offered to the highly functioning elderly with the
      expectation of a good quality of life postoperatively.

PMID- 17036204
TI  - Fecal impaction in adults: report of 30 cases of seed bezoars in the rectum.
AB  - PURPOSE: Seed bezoars in the rectum have been considered an uncommon cause of
      fecal impaction in adults. Although there have been several reports on sunflower
      seed bezoars, seed bezoars from the fruit of the prickly pear cactus and
      watermelon have received little notice. This study was designed to determine the
      frequency of fecal impaction by seed bezoars in the rectum and their clinical
      characteristics in adults. METHODS: A retrospective review of the medical records
      of patients hospitalized with the diagnosis of fecal impaction during a ten-year
      period. RESULTS: During the study period (January 1996 to December 2005), 55
      patients were hospitalized at the Western Galilee Hospital, in northern Israel,
      with the diagnosis of fecal impaction. Phytobezoars were found in 30 patients (55
      percent). The seed bezoars were composed of prickly pear seeds in 12 patients,
      watermelon seeds in 10 patients, sunflower seeds in 4 patients, popcorn kernels
      in 1 patient, and pomegranate seeds in 1 patient. The Jew:Arab ratio for seed
      bezoars was 7:23. Seventy-three patients had seedless fecal masses with a
      Jew:Arab ratio of 58:15. All 30 patients with bezoar underwent digital
      disimpaction under general anesthesia. Only 21 of 73 patients with seedless fecal
      masses were treated under general anesthesia. CONCLUSIONS: Seed bezoars found in
      the rectum were the most common cause of fecal impaction requiring
      hospitalization, probably to the result of the eating habits in the Middle East.
      The consumption of seeds with shell fragments or fruits containing many seeds
      (such as the prickly pear) should be accompanied by the awareness that large
      quantities may cause fecal impaction.

PMID- 17036205
TI  - Lower limb acute compartment syndrome after colorectal surgery in prolonged
      lithotomy position.
AB  - PURPOSE: Acute compartment syndrome in patients undergoing prolonged colorectal
      procedures is uncommon but can have catastrophic consequences for the patient
      with the development of metabolic acidosis, myoglobinuric renal failure,
      Volkmann's contracture, limb loss, and death. The potential to produce long-term
      disability in a patient has important medicolegal implications, particularly if
      the complication is avoidable. Why only some patients develop acute compartment
      syndrome is not fully understood. The purpose of this study was to highlight
      current knowledge and suggested prevention strategies. METHODS: A review of the
      relevant English language articles was performed on the basis of a MEDLINE search
      of the keywords: acute compartment syndrome, lithotomy position, reperfusion
      injury, and fasciotomy. RESULTS: Different factors play a role: lithotomy
      position with or without head down, ankle and knee position, external compression
      for deep vein thrombosis prophylaxis, method of leg support, duration of surgery,
      and physiologic factors, such as gender, age, and body mass index. All efforts
      should be directed to prevent the establishment of acute compartment syndrome and
      there are accepted suggestions, such as limiting the time of leg elevation,
      positioning the leg below the atrium level, and monitoring postoperatively
      patients at risk. There is still debate on the intraoperative use of pulse
      oximetry to detect hypoperfusion and the appropriate use of sequential
      compression devices and antithromboembolic stockings. CONCLUSIONS: Acute
      compartment syndrome is uncommon but cases have been reported after prolonged
      pelvic procedures in the lithotomy position and it is a preventable condition.
      More research is required to set clear guidelines on patient positioning during
      surgery.

PMID- 17036206
TI  - The importance of local subcutaneous fat thickness in pilonidal disease.
AB  - PURPOSE: This study was designed to investigate the local subcutaneous fat
      thickness in sacrococcygeal pilonidal disease. METHODS: Subcutaneous fat
      thickness was measured by ultrasonography in 125 patients with sacrococcygeal
      pilonidal disease and 125 age-matched, body mass index-matched and gender-matched
      controls. RESULTS: The sacrococcygeal subcutaneous fat thickness was 14.4 +/- 2.9
      mm, 18.3 +/- 3.1 mm, and 22 +/- 2.2 mm, respectively, in normal, overweight, and
      obese patients with sacrococcygeal pilonidal disease and 9.1 +/- 3.1 mm, 11.3 +/-
      2.6 mm, and 20 +/- 1.8 mm, respectively, in normal, overweight, and obese
      controls. Sacrococcygeal fat was significantly thicker in normal and overweight
      patients with pilonidal disease compared with controls with same body mass index
      (P< 0.01). There were no significant differences in fat thickness between obese
      patients and obese controls (P > 0.05). CONCLUSIONS: Sacrococcygeal fat
      thickness, as a local factor, is closely associated with pilonidal disease.

PMID- 17036208
TI  - Preoperative tegafur suppositories for resectable rectal cancer: phase II trial.
AB  - PURPOSE: Preoperative radiochemotherapy for rectal cancer causes a high rate of
      moderate-to-severe toxicities and is associated with only moderate survival
      benefits. A simpler, safer, and more convenient treatment would be preferable.
      Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were
      piloted. METHODS: A total of 129 patients with resectable rectal cancer were
      enrolled. The primary end points were pathologic response, adverse events, rate
      of sphincter-sparing surgery, recurrence, and survival. RESULTS: The total dose
      of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in
      60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate
      was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic
      leakage in 9 percent of cases. Pathologic responses were observed in 70 percent
      of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or
      more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis
      in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total
      dose that patients showing complete or two-thirds or more necrosis received was
      42.8 +/- 6.4 g (P = 0.01) compared with 31.6 +/- 1.2 g administered to patients
      showing less than two-thirds necrosis. Adverse events were observed in 15.6
      percent of patients overall, and Grade III or IV events were observed in 2.3
      percent of patients. During a median follow-up of 48 months, distant metastasis
      occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent
      of patients. The four-year, disease-free and overall survival rates were 67.6 and
      80.1 percent, respectively. CONCLUSIONS: Preoperative tegafur suppositories are
      associated with low toxicity and may lead to anal sphincter-sparing surgery with
      acceptable postoperative complications and favorable local and distal control.

PMID- 17036209
TI  - Toward a Wolbachia multilocus sequence typing system: discrimination of Wolbachia
      strains present in Drosophila species.
AB  - Among the diverse maternally inherited symbionts in arthropods, Wolbachia are the
      most common and infect over 20% of all species. In a departure from traditional
      genotyping or phylogenetic methods relying on single Wolbachia genes, the present
      study represents an initial Multilocus Sequence Typing (MLST) analysis to
      discriminate closely related Wolbachia pipientis strains, and additional data on
      sequence diversity in Wolbachia. We report a new phylogenetic characterization of
      four genes (aspC, atpD, sucB, and pdhB), and provide an expanded analysis of
      markers described in previous studies (16S rDNA, ftsZ, groEL, dnaA, and gltA).
      MLST analysis of the bacterial strains present in 16 different Drosophila
      Wolbachia associations detected four distinct clonal complexes that also
      corresponded to maximum-likelihood identified phylogenetic clades. Among the 16
      associations analyzed, six could not be assigned to MLST clonal complexes and
      were also shown to be in conflict with relationships predicted by maximum
      likelihood phylogenetic inferences. The results demonstrate the discriminatory
      power of MLST for identifying strains and clonal lineages of Wolbachia and
      provide a robust foundation for studying the ecology and evolution of this
      widespread endosymbiont.

PMID- 17036210
TI  - Phage displayed Bacillus thuringiensis Cry1Ba4 toxin is toxic to Plutella
      xylostella.
AB  - We constructed recombinant phage particles displaying the Bacillus thuringiensis
      Cry1Ba4 active toxin using the pfUSE5 and pComb3X phagemid vectors. The
      recombinant phage particles were screened and evaluated for displayed
      biologically active Cry1Ba4 toxin against the target insect larvae. Concurrent
      expression of Cry1Ba4 protoxin was carried out using the pETBlue -2 plasmid
      expression vector in Escherichia coli Tuner (DE3)pLacI and the protoxin was
      successfully expressed at a size of 129 kDa. In the bioassay, 3.30 mg crude
      extract of Cry1Ba4 protoxin, 9.35 x 10(9) TU and 7.70 x 10(9) TU of induced
      recombinant phage particles carrying Cry1Ba4 active toxin displayed on pComb3X
      and pFUSE5, respectively, demonstrated mortality of greater than 85% against
      Plutella xylostella (third-instar) within 48 hours. Thus, we have successfully
      displayed the Cry1Ba4 activated toxin on the surface of a phage and demonstrated
      toxicity towards larvae.

PMID- 17036213
TI  - A new approach to flow-batch titration. A monosegmented flow titrator with
      coulometric reagent generation and potentiometric or biamperometric detection.
AB  - Monosegmented flow analysis (MSFA) has been used as a flow-batch system to
      produce a simple, robust, and mechanized titrator that enables true titrations to
      be performed without the use of standards. This paper also introduces the use of
      coulometry with monosegmented titration by proposing a versatile flow cell.
      Coulometric generation of the titrand is attractive for titrations performed in
      monosegmented systems, because the reagent can be added without increasing the
      volume of sample injected. Also, biamperomeric and potentiometric detection of
      titration end-points can increase the versatility of the monosegmented titrator.
      The cell integrates coulometric generation of the titrand with detection of end
      point by potentiometry or biamperometry. The resulting titrator is a flow-batch
      system in which the liquid monosegment, constrained by the interfaces of the
      gaseous carrier stream, plays the role of a sample of known volume to be
      titrated. The system has been used for determination of ascorbic acid, by
      coulometric generation of I2 with biamperometric detection, and for determination
      of Fe(II), by coulometric generation of Ce(IV) with potentiometric detection of
      the end-point, both in feed supplements.

PMID- 17036211
TI  - The effect of calcium and magnesium on the activity of bovicin HC5 and nisin.
AB  - Some Gram-positive bacteria produce small peptides (bacteriocins) that have
      antimicrobial activity, but many bacteria can become bacteriocin resistant.
      Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, has the ability
      to inhibit nisin-resistant bacteria. Because nisin resistance has in many cases
      been correlated with an alteration of lipoteichoic acids or the polar head groups
      of membrane phospholipids, we decided to examine the effect of divalent cations
      on nisin and bovicin HC5 activity. Both bacteriocins catalyzed potassium efflux
      from S. bovis JB1, a non-bacteriocin-producing strain. The addition of large
      amounts (100 mM) of calcium or magnesium increased the ability of S. bovis JB1 to
      bind Congo red (an anionic dye) and counteracted bacteriocin-mediated potassium
      loss. Calcium was more effective than magnesium in decreasing nisin activity, but
      the reverse was observed with bovicin HC5. Nisin-resistant S. bovis JB1 cells
      bound three times as much Congo red as nisin-sensitive cells, and this result is
      consistent with the idea that changes in cell surface charge can be a mechanism
      of bacteriocin resistance. The nisin-resistant cells were less susceptible to
      bovicin HC5, but bovicin HC5 still caused a 50% depletion of intracellular
      potassium. These results indicate that nisin and bovicin HC5 react differently
      with the cell surfaces of Gram-positive bacteria.

PMID- 17036214
TI  - Quantitative analysis of enzymatic assays using indoxyl-based substrates.
AB  - Hydrolysis of indoxyl-based substrates by hydrolytic enzymes is a commonly used
      semiquantitative detection system that generates a water-insoluble indigo dye
      which is difficult to quantify. This work describes the quantitative analysis and
      enzyme kinetics for alkaline phosphatase (AP) and 5-bromo-4-chloro-3-indoxyl
      phosphate (BCIP) in solution obtained by applying known solubilization
      methodology from the textiles industry to the enzymatic product. This proposal is
      based on the reduction of the tetrahalo-indigo blue dye in a basic medium with
      the aim of generating its aqueous-soluble parent compound termed indigo white,
      which gives a rich yellow color in solution and is fluorescent. A quantitative
      ELISA (where a soluble end product is required) is accomplished for first time
      using BCIP as substrate.

PMID- 17036215
TI  - Detection of preclinical scrapie from serum by infrared spectroscopy and
      chemometrics.
AB  - In this study we describe a methodology for diagnosing preclinical scrapie
      infection in hamsters from serum by a combination of Fourier-transform infrared
      (FT-IR) spectroscopy and chemometrics. Syrian hamsters (Mesocricetus auratus)
      were orally inoculated with the 263K scrapie agent, or mock-infected, and sera
      were obtained at 70, 100 and 130 days post infection (dpi) and at the terminal
      stage of scrapie (160 +/- 10 dpi). The analysis of hamster sera by FT-IR
      spectroscopy and artificial neural networks (ANN) confirmed results from earlier
      studies which had indicated the existence of disease-related structural and
      compositional alterations in the sera of infected donors in the terminal stage of
      scrapie [Schmitt et al. (2002) Anal Chem 74:3865-3868]. Experimental data from
      sera of animals in the preclinical stages of scrapie revealed subtle but
      reproducible spectral variations that permitted the identification of a
      preclinical scrapie infection at 100 dpi and later, but not at 70 dpi. The IR
      spectral features that were discriminatory for the preclinical stages differed
      from those of the terminally ill individuals. In order to reliably identify
      scrapie-negative as well as preclinical (100 and 130 dpi) and terminal scrapie
      positive animals, a hierarchical classification system of independent artificial
      neural networks (ANN) was established. A "toplevel" ANN was designed which
      discriminates between animals in the terminal stage of scrapie and preclinical
      scrapie-positive or control animals. Spectra identified by the "toplevel" ANN as
      preclinical or controls were then further analyzed by a second classifier, the
      "sublevel" ANN. Using independent external validation procedures, the toplevel
      classifier produced an overall classification accuracy of 98%, while the sublevel
      classifier yielded an accuracy of 93%, indicating that scrapie-specific serum
      markers were also present for preclinical disease stages. Possible spectral
      markers responsible for the discrimination capacity of the two different ANNs are
      discussed.

PMID- 17036217
TI  - Changes in muscle strength and EMG median frequency after anterior cruciate
      ligament reconstruction.
AB  - The purpose of this study was to monitor neuromuscular changes in quadriceps
      femoris muscle at 1 and 3 months after anterior cruciate ligament reconstruction
      (ACLR). Changes in isometric muscle strength (MVC), voluntary activation and
      surface electromyogram (EMG) parameters were examined in relation to knee
      stability, pain and swelling in 31 patients (25 M, 6 F) mean (SD) 30(8) years.
      Physically inactive (RC) and sports participants (SC) acted as controls. Median
      frequency (Hz) and amplitude (mV) of rectus femoris using Fast Fourier Transform
      (FFT) 2(11) was calculated during 5-s isometric contractions at 100, 75, 50 and
      25% of MVC. One month after surgery, a significant correlation (P < 0.01) was
      found between activation (%) and MVC of injured knee extensors. By 3 months, most
      patients were pain free and had achieved full activation but still had muscle
      weakness. At 1 and 3 months post-surgery and for all levels of MVC contraction,
      the median frequencies of the injured limbs were significantly lower (P < 0.05)
      compared to the SC group as were those of the RC group. There was a significant
      lowering of the median frequencies of the uninjured limbs compared to the SC
      group at 75 and 100% of MVC. The EMG amplitude of the uninjured and injured limbs
      mirrored those of the SC and RC groups, respectively. These results support the
      view that muscle activation patterns were altered following ACL injury and
      surgical repair and may contribute to subsequent changes in muscle fibre
      properties during detraining and subsequent retraining.

PMID- 17036218
TI  - A new cytoplasmic male sterility system for hybrid seed production in Indian
      oilseed mustard Brassica juncea.
AB  - We report a novel cytoplasmic male sterility (CMS) system in Brassica juncea
      (oilseed mustard) which could be used for production of hybrid seed in the crop.
      A male sterile plant identified in a microspore derived doubled haploid
      population of re-synthesized B. napus line ISN 706 was found to be a CMS as the
      trait was inherited from the female parent. This CMS, designated '126-1', was
      subsequently transferred to ten different B. juncea varieties and lines through
      inter-specific crosses followed by recurrent backcrossing. The F(1)s of inter
      specific crosses were invariably partially fertile, but irrespective of the
      variety/line used, the recipient lines became progressively male sterile over
      five to seven generations and could be maintained by crossing the male sterile
      lines with their normal counterparts. The male sterile lines were found to be
      stable for the trait under both long and short day conditions. CMS lines when
      crossed with lines other than the respective maintainer line were restored for
      fertility, implying that any variety could act as a restorer for '126-1'
      cytoplasm in B. juncea. These unique features in maintenance and restoration of
      CMS lines coupled with near normal floral morphology of the CMS lines have
      allowed the use of '126-1' cytoplasm for hybrid seed production. The uniqueness
      of '126-1' has been further established by Southern hybridization with
      mitochondrial DNA probes and by a histological study of the development of male
      sterile anthers.

PMID- 17036219
TI  - Genetic mapping of seed shape in three populations of recombinant inbred lines of
      soybean (Glycine max L. Merr.).
AB  - Round soybean seeds are sought-after for food-type soybean. Also the genetic
      control of seed geometry is of scientific interest. The objectives of this study
      were to estimate heritability and map quantitative trait loci (QTLs) responsible
      for seed shape traits. Three densely mapped recombinant inbred populations each
      with 192 segregants were used, Minsoy x Archer, Minsoy x Noir1, and Noir1 x
      Archer. A two rep two location experiment was conducted in Los Andes, Chile, and
      East Lansing, MI, USA. Seed height (SH), width (SW), length (SL), and seed volume
      (SV) as width x height x length were measured to determine seed shape.
      Heritability was estimated by variance component analysis. A total of 19
      significant QTLs (LOD >or= 3.7) in ten linkage groups (LG) were detected for all
      the traits. Only one QTL was stable across populations and environments and six
      were stable in at least two populations in both environments. The amount of
      phenotypic variation explained by a single QTL varied from 7.5% for SH, to 18.5%
      for SW and at least 30% of the genetic variation for the traits is controlled by
      four QTL or less. All traits were highly correlated with each other in all
      populations with values ranging from 0.5 to 0.9, except for SL and SW that were
      not significantly correlated or had a low correlation in all populations. Narrow
      sense heritabilities for all traits ranged from 0.42 to 0.88. We note that LG u9,
      u11, and u14 are hot points of the genome for QTLs for various traits. The number
      and genomic distribution of the QTLs confirms the complex genetic control of seed
      shape. Transgressive segregation was observed for all traits suggesting that
      careful selection of parents with similar phenotypes but different genotypes
      using molecular markers can result in desirable transgressive segregants.

PMID- 17036216
TI  - Influence of sympathetic nervous system on sensorimotor function: whiplash
      associated disorders (WAD) as a model.
AB  - There is increasing interest about the possible involvement of the sympathetic
      nervous system (SNS) in initiation and maintenance of chronic muscle pain
      syndromes of different aetiology. Epidemiological data show that stresses of
      different nature, e.g. work-related, psychosocial, etc., typically characterised
      by SNS activation, may be a co-factor in the development of the pain syndrome
      and/or negatively affect its time course. In spite of their clear traumatic
      origin, whiplash associated disorders (WAD) appear to share many common features
      with other chronic pain syndromes affecting the musculo-skeletal system. These
      features do not only include symptoms, like type of pain or sensory and motor
      dysfunctions, but possibly also some of the pathophysiological mechanisms that
      may concur to establish the chronic pain syndrome. This review focuses on WAD,
      particular emphasis being devoted to sensorimotor symptoms, and on the actions
      exerted by the sympathetic system at muscle level. Besides its well-known action
      on muscle blood flow, the SNS is able to affect the contractility of muscle
      fibres, to modulate the proprioceptive information arising from the muscle
      spindle receptors and, under certain conditions, to modulate nociceptive
      information. Furthermore, the activity of the SNS itself is in turn affected by
      muscle conditions, such as its current state of activity, fatigue and pain
      signals originating in the muscle. The possible involvement of the SNS in the
      development of WAD is discussed in light of the several positive feedback loops
      in which it is implicated.

PMID- 17036220
TI  - Resin composites: strength of the bond to dentin versus mechanical properties.
AB  - This study (1) investigated whether the combination of an adhesive system from
      one manufacturer with a resin composite from the same manufacturer provides
      superior bonding of the resin composite to dentin compared with the combination
      of an adhesive system from one manufacturer with a resin composite from another
      manufacturer, and (2) tested for a possible influence on bond strength of
      mechanical properties of the resin composite. After application of an adhesive
      system, a resin composite was bonded to flattened human dentin and tested in
      shear after 1 week. Five adhesive systems (AdheSE, Adper Prompt L-Pop, Clearfil
      SE Bond, Optibond Solo Plus, and Xeno III) were tested with each of five resin
      composites (Tetric Ceram, Filtek Supreme, Clearfil AP-X, Premise, and EsthetX).
      The mechanical properties flexural strength and flexural modulus were determined
      by three-point loading. Bond strengths were influenced by the brand of adhesive
      system (P < 0.0001) and by the brand of resin composite (P < 0.0001), but the
      combination of an adhesive system from one manufacturer with a resin composite
      from the same manufacturer did not provide bond strengths that were superior to
      those obtained when an adhesive system from one manufacturer was combined with a
      resin composite from another manufacturer. Independent of the brand of resin
      composite, the adhesive system Clearfil SE Bond mediated the highest bond
      strength to dentin. For each adhesive system, the resin composite Clearfil AP-X
      resulted in the highest bond strength to dentin. Significant positive
      correlations were found between bond strength and flexural strength (P < 0.0026,
      r = 0.21) and between bond strength and flexural modulus (P < 0.0017, r = 0.22).

PMID- 17036221
TI  - Successful engraftment of mismatched unrelated cord blood transplantation
      following reduced intensity preparative regimen using fludarabine and busulfan.
AB  - We conducted a pilot study to evaluate the feasibility of reduced-intensity cord
      blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen
      in adult patients with advanced hematologic malignancies. Seventeen patients with
      a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial
      Hospital between April 2004 and November 2005. Preparative regimens were
      fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus
      was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of
      infused total nucleated were 2.6 x 10(7)/kg (range, 2.0-3.3). HLA disparity was
      found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases
      progressed despite preparative regimens in four patients. Of the remaining 13
      patients, nine patients achieved engraftment at a median of day 18 (range, 17
      28). Six of the nine patients with engraftment achieved complete donor-type
      chimerism by day 100. Six patients were alive in remission at median follow-up of
      13.1 months (range, 1.0-19.0). This study demonstrated the feasibility of RI-CBT
      using a non-TBI regimen in adults. When disease progression is controlled by the
      preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor
      effect. Further studies are required to identify patients who benefit from this
      regimen.

PMID- 17036222
TI  - The use of combined lateral and medial releases in the treatment of post
      traumatic contracture of the elbow.
AB  - Elbow stiffness is a common disorder, which restricts daily activities. Between
      30 degrees and 130 degrees of elbow movement is usually enough to perform most
      daily activities. However, a 10 degrees to 15 degrees loss of elbow extension may
      be a problem when the patient is an athlete. From 1996 to 2004, 20 elbows of 20
      patients (who were available for follow-up examination) were treated by lateral
      and medial release at Kocaeli University, for post-traumatic elbow contracture.
      Preoperative and the postoperative 12-month follow-up measurements were
      performed. The mean preoperative arc of motion was 35 degrees and this value
      improved to 86.2 degrees . The maximum improvement at the arc of motion was 105
      degrees . In an effort to understand the pathophysiology of the condition,
      surgical approaches may be used safely. The purpose of this study was to assess
      the functional outcome of the elbow joint after using a combination of lateral
      and medial approaches to treat elbow stiffness.

PMID- 17036223
TI  - Dynamic hip screw in the treatment of intertrochanteric fractures: a comparison
      of two fixation methods.
AB  - The study is a prospective evaluation and comparison. A minimally invasive
      Dynamic Hip Screw (MIDHS) technique is presented. One hundred and two patients
      with intertrochanteric fractures were treated with either a MIDHS or a
      conventional dynamic hip screw (CDHS). We used the Singh index as a measure of
      osteoporosis and also classified the fractures according to three different
      systems (OTA, Boyd-Griffin, and Evans). All patients were followed up for 12
      months with a hip score evaluation. The patients were divided into two groups,
      based on the method of treatment. The MIDHS group includes 42 patients with an
      average age of 72.6 years. The CDHS group includes 60 patients, with an average
      age of 71.3 years. Both groups were similar in injury mechanism, fracture types,
      mean Singh index and confounding medical condition (all p values >0.05). The CDHS
      group had significantly larger wound incision, greater haemoglobin level drop,
      higher pain level, more total analgaesic use and longer hospital stay than the
      MIDHS group (all p values<0.05). The hip score, union rate, healing time,
      adequate reduction and adequate screw position rate was not significantly
      different between the two groups (all p values >0.05). In conclusion, either a
      MIDHS or a CDHS in the treatment of intertrochanteric fractures is an effective,
      simple and safe method. The mini-invasive technique as opposed to the
      conventional technique has smaller wound size, lower pain level, and lower blood
      loss. Hospital stay and total analgaesic use were decreased, benefitting the
      patient and reducing hospital cost.

PMID- 17036225
TI  - Complementary and alternative medicines for use in supportive care in pediatric
      cancer.
AB  - INTRODUCTION: Complementary and alternative medical practices (CAM) are being
      used by increasing numbers of children with cancer. DISCUSSION: Recent surveys
      report CAM use prevalence rates of 24-90% in children with cancer. Interest in
      supporting children through the side effects or stress of conventional treatment
      has been described as one of the major motivating factors for the use of CAM
      therapies. Research is difficult secondary to the complexity of the therapies and
      lack of standardization. However, several research studies investigating CAM
      therapies for supportive care in children with cancer are ongoing. Information on
      several studies in progress through the Children's Oncology Group and other
      institutions will be reviewed. CONCLUSION: The progress made in the development
      of these studies demonstrates that CAM therapies can be investigated for their
      supportive care roles in the therapy of children with cancer.

PMID- 17036224
TI  - Intraoperative electrostimulation objectifies the assessment of functional nerve
      preservation after mesorectal excision.
AB  - BACKGROUND: To improve nerve-sparing surgery, intraoperative electrical
      stimulation of pelvic autonomic nerves (INS) has been proposed in urology,
      gynecology, and visceral surgery. The aim of this study was to assess the impact
      of INS while monitoring intravesical pressure on the accurate evaluation of
      pelvic autonomic nerve preservation (PANP) after mesorectal excision. It was
      sought to determine whether this confirmation is useful in the prediction of
      postoperative urinary function. METHODS: Sixty-two patients with mesorectal
      exzision for rectal cancer were examined prospectively. PANP was assessed
      visually by the surgeon and with INS. Bladder function was evaluated by post
      voiding residual volume measurement, rate of recatheterization, rate of long-term
      urinary catheterisation, and the international prostatic symptom score with
      quality of life index. RESULTS: INS confirmed bilateral preservation of
      parasympathetic nerves in 46 patients (74%), and in 10 patients (16%) in at least
      one side. In six patients (10%), INS failed to confirm PANP. Eleven patients
      (18%) developed urinary symptoms postoperatively. INS results had a higher
      sensitivity than visual assessment by the surgeon (82 vs 46%). Values for
      specificity ranged at 90 and 92%, respectively. Accuracy of INS in predicting
      PANP was higher (88 vs 83%). The correlation between urinary function and the
      findings on INS was good (kappa-value: 0.65), correlation between urinary
      function and visual assessment by the surgeon was fair (kappa-value: 0.40).
      CONCLUSION: INS, while monitoring intravesical pressure, accurately predicts
      bladder function after mesorectal excision. It may provide further insight into
      pelvic autonomic nerve sparing techniques.

PMID- 17036226
TI  - Does granulocyte transfusion play a role in the multidisciplinary treatment of
      invasive mycosis?

PMID- 17036227
TI  - Early thermal history significantly affects the seasonal hyperplastic process
      occurring in the myotomal white muscle of Dicentrarchus labrax juveniles.
AB  - The effect of early (embryonic and larval) thermal history on subsequent
      (juvenile) white muscle hyperplasia was studied in a teleost fish, the European
      sea bass (Dicentrarchus labrax L.). D. labrax, incubated and reared at constant
      temperatures of 13 degrees C, 15 degrees C or 20 degrees C from the embryonic
      stage of half epiboly up to 18-19 mm in total length, were transferred to ambient
      seawater temperature and reared for the subsequent 14 months on commercial feed.
      The somatic growth of juveniles was linked to annual variations of ambient
      seawater temperature and inversely related to early rearing temperature, so that,
      after 14 months, the juveniles originally reared at low temperatures had
      compensated for the growth retardation experienced during early life. The white
      muscle growth process of juveniles was quantified after two periods of growth
      opportunity at ambient seawater temperature (100 and 400 days post-transfer) as
      well as, in order to follow total-length-dependent effects of early temperature
      and to discriminate total-length-independent effects of early temperature, on
      juveniles from the three batches sampled at six successive equivalent total
      lengths (31-33, 84-88, 141-145, 166-172, 196-206 and 211-220 mm). Our data
      demonstrate the existence of a seasonal recruitment of new white muscle fibres
      when seawater temperature increases and of a shrinkage of the largest white
      muscle fibres during the winter months. The seasonal recruitment of new white
      muscle fibres occurring in juveniles is linked to their early rearing
      temperature. Juveniles originating from low temperatures have a higher and longer
      capacity to recruit new white muscle fibres when seawater temperature increases,
      supporting their better somatic growth. This finding is discussed in relation to
      the early (embryonic and larval) myogenic processes of the three populations and
      is related to their sex ratio.

PMID- 17036228
TI  - Association between the muscle-specific proteins desmin and caveolin-3 in muscle
      cells.
AB  - The muscle-specific intermediate filament protein desmin is expressed in
      mononucleated myoblasts and in differentiated myotubes. Desmin has been shown to
      associate with the sarcolemma in specific structures, such as neuromuscular
      junctions and the dystrophin-associated protein complex. Since these are
      specialized membrane regions, the study of a possible association between desmin
      and liquid-ordered membrane microdomains is of particular interest. We have
      carried out an analysis of the association between desmin and the muscle-specific
      protein caveolin-3, a major component of caveolar microdomains. Our results
      demonstrate that (1) desmin precisely co-localizes with caveolin-3 in myoblasts
      and multinucleated myotubes, (2) caveolin-3 is up-regulated during in vitro chick
      muscle development, (3) desmin is detectable in caveolae-enriched membrane
      fractions prepared from skeletal muscle, and (4) caveolin-3 co-immunoprecipitates
      with desmin. We have thus shown, for the first time, an association between the
      intermediate filament protein desmin and caveolin-3 in myogenic cells.

PMID- 17036229
TI  - Differential expression of several molecules of the extracellular matrix in
      functionally and developmentally distinct regions of rat spinal cord.
AB  - We have examined the regional distribution of several chondroitin sulfate
      proteoglycans (neurocan, brevican, versican, aggrecan, phosphacan), of their
      glycosaminoglycan moieties, and of tenascin-R in the spinal cord of adult rat.
      The relationships of these molecules with glial and neuronal populations,
      identified with appropriate markers, were investigated by using multiple
      fluorescence labeling combined with confocal microscopy. The results showed that
      the distribution of the examined molecules was similar at all spinal cord levels
      but displayed area-specific differences along the dorso-ventral axis, delimiting
      functionally and developmentally distinct areas. In the gray matter, laminae I
      and II lacked perineuronal nets (PNNs) of extracellular matrix and contained low
      levels of chondroitin sulfate glycosaminoglycans (CS-GAGs), brevican, and
      tenascin-R, possibly favoring the maintenance of local neuroplastic properties.
      Conversely, CS-GAGs, brevican, and phosphacan were abundant, with numerous thick
      PNNs, in laminae III-VIII and X. Motor neurons (lamina IX) were surrounded by
      PNNs that contained all molecules investigated but displayed various amounts of
      CS-GAGs. Double-labeling experiments showed that the presence of PNNs could not
      be unequivocally related to specific classes of neurons, such as motor neurons or
      interneurons identified by their expression of calcium-binding proteins
      (parvalbumin, calbindin, calretinin). However, a good correlation was found
      between PNNs rich in CS-GAGs and the neuronal expression of the Kv3.1b subunit of
      the potassium channel, a marker of fast-firing neurons. This observation confirms
      the correlation between the electrophysiological properties of these neurons and
      the specific composition of their microenvironment.

PMID- 17036230
TI  - Ontogeny of the GnRH systems in zebrafish brain: in situ hybridization and
      promoter-reporter expression analyses in intact animals.
AB  - The ontogeny of two gonadotropin-releasing-hormone (GnRH) systems, salmon GnRH
      (sGnRH) and chicken GnRH-II (cGnRH-II), was investigated in zebrafish (Danio
      rerio). In situ hybridization (ISH) first detected sGnRH mRNA-expressing cells at
      1 day post-fertilization (pf) anterior to the developing olfactory organs.
      Subsequently, cells were seen along the ventral olfactory organs and the
      olfactory bulbs, reaching the terminal nerve (TN) ganglion at 5-6 days pf. Some
      cells were detected passing posteriorly through the ventral telencephalon (10-25
      days pf), and by 25-30 days pf, sGnRH cells were found in the
      hypothalamic/preoptic area. Continuous documentation in live zebrafish was
      achieved by a promoter-reporter expression system. The expression of enhanced
      green fluorescent protein (EGFP) driven by the sGnRH promoter allowed the earlier
      detection of cells and projections and the migration of sGnRH neurons. This
      expression system revealed that long leading processes, presumably axons,
      preceded the migration of the sGnRH neuron somata. cGnRH-II mRNA expressing cells
      were initially detected (1 day pf) by ISH analysis at lateral aspects of the
      midbrain and later on (starting at 5 days pf) at the midline of the midbrain
      tegmentum. Detection of red fluorescent protein (DsRed) driven by the cGnRH-II
      promoter confirmed the midbrain expression domain and identified specific
      hindbrain and forebrain cGnRH-II-cells that were not identified by ISH. The
      forebrain DsRed-expressing cells seemed to emerge from the same site as the sGnRH
      EGFP-expressing cells, as revealed by co-injection of both constructs. These
      studies indicate that zebrafish TN and hypothalamic sGnRH cell populations share
      a common embryonic origin and migratory path, and that midbrain cGnRH-II cells
      originate within the midbrain.

PMID- 17036231
TI  - Block of mitochondrial apoptotic pathways in lizard ovarian follicle cells as an
      adaptation to their nurse function.
AB  - Pyriforms are ovarian follicle nurse cells that undergo apoptosis at the end of
      previtellogenesis and are completely eliminated by the epithelium. This event is
      accompanied by the active transfer of organelles and macromolecules to the oocyte
      via an intercellular bridge. Since it would be a nonsense for damaged
      mitochondria to reach the oocyte, we have postulated that pyriform cells have
      adapted their apoptotic machinery to prevent mitochondrial degradation. To verify
      this hypothesis, we have studied mitochondrial morphology and functionality
      during follicle cell regression. Cytological and biochemical evidence indicates
      that mitochondria in pyriforms maintain their size, organization and membrane
      potential. This clearly indicates that they are not involved in apoptosis
      signalling/progression. This block would favour both the oocyte, by increasing
      the pool of organelles available from follicle cells, and also the regressing
      pyriforms, by maintaining the energy resources required for completion of their
      nurse function. The block is probably attributable to an over-expression of Bcl-2
      and might be carried out by sequestering cytochrome c inside the organelles. As
      demonstrated by in vitro experiments, the mitochondrial apoptosis pathway can be
      activated by stress induction, such as serum deprivation, but not following
      physiological pro-apoptotic signalling, such as treatment with gonadotrophin
      releasing hormone.

PMID- 17036232
TI  - Customized imaging for children and obese people: key issues and strategies.

PMID- 17036233
TI  - [The influence of proprioceptive insoles (Bourdiol) on the sagittal curvature and
      inclination of the trunk].
AB  - Proprioceptive insoles rely on the concept of Rene-Jaques Bourdiol, a French
      neurologist. The aim is to modulate plantar surface sensibility and to influence
      posture and statics of patients: it is hypothesized that the effect of modified
      afferent sensory input through proprioceptive stimulation of terminal muscle
      chains will have either a relaxing or stimulating effect on the whole body, which
      may be realized by affecting the posture. Small pads with a thickness of
      typically 1-3 mm are embedded into the insole to provide a specific stimulation.
      In fitting the insoles selectively to the individual patient the effect of the
      insoles on the trunk posture is taken as a feedback. This study investigates the
      influence of proprioceptive insoles on the sagittal curve in 20 selected
      patients. The protocol used a repeated measures research design. The measures of
      the sagittal curve were obtained using raster stereography. The four different
      conditions were: (1) barefoot, (2) convenient shoes without the insoles, (3) the
      same shoes with a placebo insole, and (4) the same shoes with neurological
      insoles. Evaluation of raster stereographs provided the kyphotic angle between T4
      and T12 and lordotic angle between T12 and S1. Statistical evaluation was
      performed with the t-test for paired measurements. No significant differences
      were found in the sagittal profile. Only trunk inclination in normal posture was
      found to yield a significant difference (0.38 degrees) between placebo and
      neurological insoles. However, no clear statement on the efficiency of
      neurological insoles can be made.

PMID- 17036234
TI  - [Significance of microbial colonisation in materials for orthopaedic technology.
      New insights].
AB  - A great problem in the treatment of diabetes are infections of diabetic feet. A
      likely reservoir of microorganisms are contaminated orthopaedic materials.
      Insoles from 70 patients were examined for potential microbial colonisation.
      Commonly employed materials were contaminated in vitro under standardised
      conditions using known microorganisms. After treating with an alcoholic skin
      disinfectant, the organisms were counted semiquantitatively. In addition to
      pathogens, the surfaces showed mainly microorganisms present in the normal skin
      flora. In all materials tested, disinfection reduced the number of organisms by 4
      5 log orders. It could be shown that simple disinfection (wiping) reduces the
      microorganisms present on orthopaedic materials to an acceptable number. Further
      studies are needed to determine whether this also reduces the incidence of
      diabetic skin and soft tissue infection.

PMID- 17036236
TI  - Localized basal meningeal enhancement in tuberculous meningitis.
AB  - BACKGROUND: Focal basal meningeal enhancement may produce a confusing CT picture
      in children with suspected tuberculous meningitis (TBM). OBJECTIVE: To
      demonstrate the incidence, distribution and appearance of localized basal
      meningeal enhancement in children with TBM. MATERIALS AND METHODS: CT scans of
      patients with definite (culture proven) and probable (CSF suggestive) TBM were
      retrospectively evaluated by two observers. Localized basal enhancement was
      documented as involving: unilateral cistern of the lateral fossa (CLF),
      unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination,
      unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern
      and isolated quadrigeminal plate cistern. RESULTS: The study included 130
      patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement
      was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly,
      followed by the lateral fossa cistern. The ambient cistern was involved in three
      patients and the quadrigeminal plate cistern in one. Focal areas of enhancement
      corresponded to the areas of infarction in every patient. CONCLUSION: Focal basal
      meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in
      mind when evaluating CT scans in children presenting with focal neurological
      findings, seizures or meningism in communities where TBM is endemic.

PMID- 17036235
TI  - Using multidetector-row CT in neonates with complex congenital heart disease to
      replace diagnostic cardiac catheterization for anatomical investigation: initial
      experiences in technical and clinical feasibility.
AB  - BACKGROUND: Echocardiography is the first-line modality for the investigation of
      neonatal congenital heart disease. Diagnostic cardiac catheterization, which has
      a small but recognized risk, is usually performed if echocardiography fails to
      provide a confident evaluation of the lesions. OBJECTIVE: To verify the technical
      and clinical feasibilities of replacing diagnostic cardiac catheterization with
      multidetector-row CT (MDCT) in neonatal complex congenital heart disease.
      MATERIALS AND METHODS: Over a 1-year period we prospectively enrolled all
      neonates with complex congenital heart disease referred for diagnostic cardiac
      catheterization after initial assessment by echocardiography. MDCT was performed
      using a 40-detector-row CT scanner with dual syringe injection. A
      multidisciplinary congenital heart disease team evaluated the MDCT images and
      decided if further diagnostic cardiac catheterization was necessary. The accuracy
      of MDCT in detecting separate cardiovascular anomalies and bolus geometry of
      contrast enhancement were calculated. RESULTS: A total of 14 neonates were
      included in the study. No further diagnostic cardiac catheterization was needed
      in any neonate. The accuracy of MDCT in diagnosing separate cardiovascular
      anomalies was 98% (53/54) with only one atrial septal defect missed in a patient
      with coarctation syndrome. The average cardiovascular enhancement in evaluated
      chambers was 471 HU. No obvious beam-hardening artefact was observed. CONCLUSION:
      The technical and clinical feasibility of MDCT in complex congenital heart
      disease in neonates is confirmed. After initial assessment with echocardiography,
      MDCT could probably replace diagnostic cardiac catheterization for further
      anatomical clarification in neonates.

PMID- 17036237
TI  - Prenatal MR imaging of a meconium pseudocyst extending to the right subphrenic
      space with right lung compression.
AB  - Meconium pseudocyst results from a loculated inflammation occurring in response
      to spillage of meconium into the peritoneal cavity after a bowel perforation.
      Certain cystic lesions, such as abscesses and dermoid and epidermoid cysts, are
      known to show reduced water diffusion on DWI. MRI has recently become a valuable
      adjunct to ultrasonography for fetal gastrointestinal anomalies. Complementary to
      ultrasonography, prenatal MRI can help further characterize the lesion and can
      clearly demonstrate the anatomical relationship between the lesion and adjacent
      organs. We report a case of meconium pseudocyst that was prenatally imaged with
      ultrasonography and MRI, postnatally complicated by pneumoperitoneum, and proved
      by postnatal surgery and histopathology. We emphasize the MRI of the pseudocyst,
      particularly T1-weighted and diffusion-weighted imaging.

PMID- 17036243
TI  - Familial amyotrophic lateral sclerosis: a SOD1-unrelated Japanese family of
      bulbar type with Bunina bodies and ubiquitin-positive skein-like inclusions in
      lower motor neurons.
AB  - We describe a new family with adult onset amyotrophic lateral sclerosis (FALS),
      in which the disease was characterized clinically by relatively rapid progression
      of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed
      in one patient showed no mutations. Autopsy of another patient demonstrated
      degenerative changes restricted to the upper and lower motor neuron systems; no
      evident changes were observed in the posterior column, Clarke's column or
      spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive
      skein-like inclusions in the lower motor neuron was of considerable interest.
      Cases of FALS with such pathological features are quite rare in the literature.
      Identification of the gene responsible for the disease is desirable in order to
      shed further light on the molecular pathology of not only familial, but also
      sporadic, ALS.

PMID- 17036244
TI  - Assessing the cognitive impact of Alzheimer disease pathology and vascular burden
      in the aging brain: the Geneva experience.
AB  - The progressive development of Alzheimer disease (AD)-related lesions, such as
      neurofibrillary tangles (NFT), amyloid deposits and synaptic loss, and the
      occurrence of microvascular and small macrovascular pathology within the cerebral
      cortex are conspicuous neuropathologic features of brain aging. Recent
      neuropathologic studies strongly suggested that the clinical diagnosis of
      dementia depends more on the severity and topography of pathological changes than
      on the presence of a qualitative marker. However, several methodological
      problems, such as selection biases, case-control design, density-based measures
      and masking effects, of concomitant pathologies persisted. In recent years, we
      performed several clinicopathologic studies using stereological counting of AD
      lesions. In order to define the cognitive impact of lacunes and microvascular
      lesions, we also analyzed pure vascular cases without substantial AD pathology.
      Our data revealed that total NFT numbers in the CA1 field, cortical microinfarcts
      and subcortical gray matter lacunes were the stronger determinants of dementia.
      In contrast, the contribution of periventricular and subcortical white matter
      demyelinations had a modest cognitive effect even in rare cases with isolated
      microvascular pathology. Importantly, in cases with pure AD pathology, more than
      50% of Clinical Dementia Rating scale variability was not explained by NFT,
      amyloid deposits and neuronal loss in the hippocampal formation. In cases with
      microvascular pathology or lacunes, this percentage was even lower. The present
      review summarizes our data in this field and discusses their relevance within the
      theoretical framework of the functional neuropathology of brain aging and with
      particular reference to the current efforts to develop standardized
      neuropathological criteria for mixed dementia.

PMID- 17036245
TI  - Parasite diversity of sticklebacks from the Baltic Sea.
AB  - In the brackish Baltic Sea, the species richness and diversity of parasite
      communities of three- (Gasterosteus aculeatus) and nine-spined sticklebacks
      (Pungitius pungitius) were investigated. The studies regarded four localities at
      the Schleswig-Holstein and Mecklenburg coasts, northern Germany, where salinities
      were between 10 and 18 per thousand. Species richness was relatively high,
      attaining 15 parasite species in G. aculeatus and 16 in P. pungitius, which are
      only surpassed by former investigations that lasted a year or more. An analysis
      of parasite species identity revealed clear differences in diverse localities
      referring to different supracommunities. The infracommunity comprised maximally
      of eight species in G. aculeatus and seven in P. pungitius, which corresponds to
      former investigations. The mean value of infracommunity with 5.3 parasites is the
      highest value ever found in small-sized fish. An infracommunity index revealed
      that the digenean Podocotyle atomon and Magnibursatus caudofilamentosa and the
      copepod Thersitina gasterostei were the most abundant parasites. The relationship
      of component community to mean infracommunity can judge about the threshold
      level, which allows parasite to settle successfully. An important factor to form
      parasite communities is the season of their appearance, which depends also on
      their reproduction and on the presence of intermediate hosts. In addition, the
      choice of prey (for passive infection) and quality of habitats (for active
      infection) influences the constitution of the parasite communities. The diversity
      values of parasites were low in all hosts, which is due to the brackish milieu
      and by different levels of eutrophication, which both create extreme
      environments. These do not mirror in every case the biodiversity of the
      respective habitats. The parasite community was in a level of early heterotrophic
      succession where low diversity is combined with high population density, which is
      characteristic for extreme environments. Therefore, intraspecific competition
      dominates and niches are wide. Under this aspect and regard of the actually valid
      definition that niches are dynamic systems between organisms and environment, the
      theory of vacant niches of some authors can be rejected.

PMID- 17036246
TI  - Special issue dedicated to Bodo Christ.

PMID- 17036247
TI  - [Relaparoscopy as an alternative to laparotomy for laparoscopic complications].
AB  - In the field of visceral surgery, complications requiring reintervention
      following laparoscopy are currently most likely to be approached with
      conventional laparotomy. However, relaparoscopy has the theoretical advantage of
      maintaining the reduced morbidity allowed by the first procedure. Essential to
      the success of relaparoscopy is a clear understanding of the various specific
      complications. Should the surgeon decide on relaparoscopy, then prompt action is
      of central importance. Following laparoscopic cholecystectomy, it is
      fundamentally technically possible through renewed laparoscopy to treat not only
      subhepatic abscesses but also smaller lesions of the bile duct, for example from
      the gall bladder fossa. Revision of complications following fundoplication is
      technically very demanding and should be performed only by those most experienced
      in the techniques of laparoscopy. In contrast to interventional drainage,
      relaparoscopy of abscesses following laparoscopic appendectomy has the
      theoretical advantage of allowing recognition and treatment of the causes, for
      example in the case of appendicular stump insufficiency. Relapses very shortly
      after endoscopic surgery of inguinal herniae result from erroneous technique and
      may be corrected endoscopically in most cases. Complications following colon
      surgery have so far been dealt with using open surgery for technical reasons and
      also for patient safety. Given the uncertainty in the literature, patient safety
      must be paramount, when deciding on which technique is best to employ,
      particularly in cases of haemorrhage.

PMID- 17036248
TI  - [PTA and stent placement distal to the superficial femoral artery].
AB  - Although angioplasty and stent applications in the iliac vessels and the
      superficial femoral artery have become routine procedures, their usefulness for
      the treatment of lesions of the popliteal artery and the lower leg arteries is
      still under discussion. For the popliteal artery, limitations are mainly due to
      the high mechanical stress in this area, causing high traction forces. Moreover,
      beyond the occlusive atherosclerotic changes, specific pathological entities such
      as aneurysms, emboli, entrapment syndromes, and cystic adventitial disease have
      to be differentiated. There is hope that the development of innovative stent
      designs with high flexibility might overcome the limitations. For lesions of the
      lower leg arteries treatment with percutaneous transluminal angioplasty (PTA) has
      become the method of choice. However, stent designs as used for cardiac
      interventions have been adapted for their application below the knee, and first
      encouraging results may help to justify their broad use in the future. Regarding
      PTA, innovative equipment and techniques for the treatment of arterial lesions
      below the knee include dedicated, long, and very flexible balloons, cutting
      balloon cryoplasty, and laser angioplasty. Regarding stents, bare metal stents,
      stents with passive or active coatings, and bioabsorbable stents have all been
      successfully used.

PMID- 17036249
TI  - [The side effects of antiretroviral therapy].
AB  - The introduction of highly active antiretroviral therapy (HAART) has resulted in
      tremendous improvements in morbidity and mortality in HIV-infected patients.
      However, the use of these drugs has coincided with an increasing number of
      reports of gastrointestinal, hepatic or metabolic side effects. Soon after
      beginning antiretroviral treatment drug rashes, hypersensitivity reactions,
      immune reconstitution syndrome or injection site reaction are frequently seen.
      Under HAART dyslipidemia, impaired glucose metabolism and elevated liver function
      are observed. In the later treatment phase, lipodystrophy, a combination of
      peripheral lipoatrophy and central fat accumulation, occurs.

PMID- 17036250
TI  - [HIV-associated tumors].
AB  - In the beginning of the HIV epidemic, Kaposi sarcoma was a common stigma in AIDS
      patients and one of the leading causes of death. While Kaposi sarcoma is seen
      less frequently since the introduction of antiretroviral therapy, lymphoma and
      other malignancies are an increasing therapeutic challenge. The incidence of HPV
      related anal carcinoma and its precursor lesions is rising so dramatically that
      screening programs as they are already established for cervical carcinoma should
      be implemented. The role of HPV in UV-associated tumors is not yet determined.
      Additional risk factors like smoking and HCV co-infection seem to play important
      roles in the high incidence of lung and hepatocellular carcinomas. While fewer
      patients die from opportunistic infections, we face a growing problem with
      malignancies in HIV-positive patients.

PMID- 17036252
TI  - The impact of mental illness on quality of life: A comparison of severe mental
      illness, common mental disorder and healthy population samples.
AB  - Patient-centred outcomes such as quality of life (QOL) are valued and used
      extensively in mental healthcare evaluations, but concerns remain about their
      practical application due to perceived measurement issues, including
      responsiveness and relationships with objective indicators and depression.
      Evidence from general population studies challenge some assumptions, suggesting
      that measurement difficulties might relate to the characteristics of mental
      health samples, rather than measurement itself. This paper assesses the impact of
      mental illness on QOL and its measurement, examining whether the life-conditions,
      opportunities and QOL of different mental health-status groups vary, and if
      explanatory models of domain-specific and global QOL differ. Objective life
      conditions, access to life-opportunities and subjective QOL were assessed over 2
      years, using the same methodology in severe mental illness (SMI; n = 149
      (baseline)/n = 126 (follow-up)), common mental disorder (CMD; n = 794/354) and no
      disorder (n = 1119/583) groups. Objective life-conditions were worse in the SMI
      group than in mentally healthy population and CMD groups, but the opportunities
      available to the SMI group were no more restricted than the CMD group. Subjective
      QOL ratings reflected this; SMI group scores were lower than the healthy
      population and in some life-domains the CMD group. Models of QOL suggested that
      life-quality was explained differently in the three groups. QOL studies combining
      mental health samples should control for health-status group, and domain-specific
      and global indicators of lifestyle and opportunity.

PMID- 17036254
TI  - Psychometric properties of the Japanese version of the Quality Of Life-Cancer
      Survivors Instrument.
AB  - The purpose of this study was to describe the psychometric properties of the
      Japanese version of the Quality of Life-Cancer Survivors Instrument (QOL-CS-J)
      developed in the U.S. This study was conducted as a mail survey to survivors of
      more than 5 years post curative resection for non-small-cell lung cancer (NSCLC)
      and who had participated in an earlier survey. This survey included the medical
      and demographic factors, the QOL-CS scores, and the Medical Outcome Study 36-Item
      Short Form (SF-36). A total of 113 survivors completed the survey. To confirm the
      reliability, the Cronbach's alpha coefficient of each subscale was calculated as
      an internal consistency (alpha = 0.65-0.89). To confirm the validity of the trial
      as conducted, Pearson's correlation coefficients between the subscales of the QOL
      CS and the subscales of the SF-36 were calculated. There were moderate
      correlations between associated subscales including QOL-CS physical to SF-36
      bodily pain (r = 0.45) and vitality (r = 0.52), QOL-CS psychological to SF-36
      mental health (r = 0.55), QOL-CS social to SF-36 general health perception (r =
      0.31) and mental health (r = 0.47), and QOL-CS total to each subscale of SF-36 (r
      = 0.25-0.64). Findings demonstrated that the QOL-CS-J adequately measured the QOL
      in long-term NSCLC survivors.

PMID- 17036253
TI  - Health-related quality of life among disease-free stomach cancer survivors in
      Korea.
AB  - Previous studies about the quality of life (QOL) in stomach cancer survivors
      focused on selected clinical parameters and did not consider the broader
      implications for overall health and QOL. We evaluated the impact of demographic
      and treatment-related factors on the QOL of stomach cancer survivors. We asked
      391 stage I-III stomach cancer survivors who had been disease-free for at least 1
      year after surgery to complete a demographic questionnaire, the European
      Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, and its
      stomach module, QLQ-STO22.Survivors undergoing total gastrectomy reported greater
      eating restrictions than those undergoing subtotal gastrectomy. Receiving
      chemotherapy or radiotherapy did not significantly affect any QLQ-C30 or QLQ
      STO22 scores. Role and emotional functioning improved with increasing age, and
      stomach-specific symptoms (pain, eating restrictions, and anxiety) lessened.
      Compared with female survivors, male survivors had better physical and role
      functioning. Smoking status was also a significant negative predictor of physical
      functioning and anxiety. Comorbidities and selected demographic characteristics
      had a greater effect than type of treatment on the QOL of post-operative stomach
      cancer patients.

PMID- 17036255
TI  - A comparison of traditional and Rasch cut points for assessing clinically
      important change in health-related quality of life among patients with asthma.
AB  - BACKGROUND: Patient-perceived change in health-related quality of life (HRQoL)
      domains has often been classified using a 15-point patient transition rating
      scale. However, traditional change levels of trivial ( - 1, 0, or 1), minimal (2,
      3 or - 2, - 3), moderate (4, 5 or - 4, - 5) and large (6, 7 or - 6, - 7) on this
      scale have been arbitrarily defined and originally assumed that change related to
      an improvement was the same as that for a decline. OBJECTIVE: To compare
      traditional and Rasch partial credit model-derived cut points and the mean
      changes for each change categorization when assessing clinically important change
      in asthma-specific HRQoL. METHODS: Our sample included 396 asthmatic outpatients
      who completed bimonthly telephone interviews on the Asthma Quality of Life
      Questionnaire and transition rating items over 1 year of participation. We
      employed item response theory in a novel approach to identify cut points on
      domain-specific HRQoL change data and transition ratings. After determining
      natural cut points for minimal, moderate, and large differences on the transition
      rating anchor, we calculated mean changes under change categorizations for both
      improvements and declines for the two transition rating classification
      approaches. RESULTS: Although traditional and Rasch categorizations for small,
      moderate, and large changes slightly differed and displayed a lack of symmetry
      between improvements and declines, nearly all mean changes between classification
      approaches were comparable. CONCLUSIONS: In this study, traditional transition
      rating cut points remain suitable to assess HRQoL clinical significance in
      outpatients with asthma.

PMID- 17036256
TI  - Assessment of traffic noise pollution from 1989 to 2003 in Lanzhou City.
AB  - On the basis of the continuous traffic noise data observed at 142 sites
      distributed in 52 roads from 1989 to 2003, the characteristics of traffic noise
      and effect factors were analyzed through traffic noise indices, such as Lep, L10,
      L50, L90, TNI, and Pn. Our findings allow us to reach a number of conclusions as
      follows: Firstly, traffic noise pollution was serious, and its fluctuant
      characteristic was obvious, resulting in a great intrusion to public in Lanzhou
      City during last 15 years. Secondly, traffic noise made a distinction between
      trunk lines and secondary lines, west-east direction roads and north-south
      direction roads. Thirdly, spatial character and time rule of traffic noise were
      obvious. In addition, traffic volume, traffic composition, road condition, and
      traffic management were identified as the key factors influencing traffic noise
      in this city.

PMID- 17036257
TI  - Monitoring of pesticide residues in fruits.
AB  - Fruit samples of ber, grapes and guava analysed for pesticide residues employing
      multiresidue analysis by gas liquid chromatography equipped with ECD and NPD
      detectors and capillary columns showed contamination with organochlorine,
      synthetic pyrethroid and organophosphate insecticides. Among organochlorines,
      HCH, DDT and endosulfan were detected in almost all the samples. Residues of HCH
      and DDT were maximum in ber followed by grapes and guava where as of endosulfan
      were maximum in guava followed by grapes and ber. All the fruit samples showed
      the presence of residues with one or the other group of pesticides. Residues of
      none of the pesticides exceeded the MRL values in any sample. On the basis of
      these studies, it is suggested that monitoring studies should be extended to
      other fruits grown in different agro climatic regions which may serve as basis
      for future policy in chemical use.

PMID- 17036258
TI  - Estimating the rate of poisoning by insecticide-treated seeds in a bird
      population.
AB  - Poisonings of granivorous birds by cereal seed treatments have been reported in
      the UK, but the true frequency of poisonings is unknown. We aimed to measure the
      rate of mortality due to poisoning by seed treatments in woodpigeons (Columba
      palumbus) in an area of East Anglian farmland where the risk from these compounds
      appeared high. Woodpigeons were fitted with temperature-sensing radio-tags and
      monitored daily during the winters of 1994/95 and 1995/96. Birds' deaths were
      detected and attempts made to retrieve carcasses for post-mortem examination
      including, where possible, analysis for pesticide residues. Ninety-one
      woodpigeons were monitored. Eleven birds died, but the causes of their deaths
      were uncertain: one contained a low residue of insecticide and in the other ten
      cases, no carcass was recovered, so no analysis was possible. Therefore, the
      number poisoned by pesticides could lie anywhere between zero and eleven. During
      1994/95, estimated mortality ranged from 0% to 52%, depending on how many (if
      any) of the 11 casualties were poisoned. During 1995/96 there were no casualties.
      Using conservative diagnostic rules for classifying birds as poisoned by OP seed
      treatments, no link was found between the availability of treated fields in the
      study area and the rate of poisonings, and there were no significant differences
      between the two study years. For reasons discussed in the paper, true mortality
      resulting from exposure to insecticide seed treatments was considered likely to
      lie in the range 0-5%.

PMID- 17036259
TI  - Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not
      associated with response to electroconvulsive therapy in major depressive
      disorder.
AB  - The aim of the present study was to examine an association of brain-derived
      neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to
      electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study
      group consisted of 119 patients consecutively admitted for ECT in the Department
      of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic
      criteria of DSM-IV for MDD. ECT was administered three times a week with a brief
      pulse constant current device. The Montgomery and Asberg Depression Rating Scale
      (MADRS) was used as an outcome measure of depression. Genotyping was performed
      using fluorescent allele-specific TaqMan probes. No association between either
      G196A or C270T and the response to ECT was found in the whole population. There
      were no significant differences in responses between men and women or between
      psychotic and non-psychotic patients. However, within subgroups such as in
      psychotic and in late-onset depression CC genotype of C270T may predict good
      response. BDNF may not be associated with response to ECT in general, but some
      association in subgroups may exist.

PMID- 17036260
TI  - Deficit of social cognition in subjects with surgically treated frontal lobe
      lesions and in subjects affected by schizophrenia.
AB  - The ability of humans to predict and explain other people's behaviour by
      attributing independent mental states such as desires and beliefs to them, is
      considered to be due to our ability to construct a "Theory of Mind". Recently,
      several neuroimaging studies have implicated the medial frontal lobes as playing
      a critical role in a dedicated "mentalizing" or "Theory of Mind" network in the
      human brain. In this study we compare the performance of patients with right and
      left medial prefrontal lobe lesions in theory of mind and in social cognition
      tasks, with the performance of people with schizophrenia. We report a similar
      social cognitive profile between patients with prefrontal lobe lesions and
      schizophrenic subjects in terms of understanding of false beliefs, in
      understanding social situations and in using tactical strategies. These findings
      are relevant for the functional anatomy of "Theory of Mind".

PMID- 17036261
TI  - Digestibility of resistant starch containing preparations using two in vitro
      models.
AB  - BACKGROUND: Resistant starch (RS) is known for potential health benefits in the
      human colon. To investigate these positive effects it is important to be able to
      predict the amount, and the structure of starch reaching the large intestine. AIM
      OF THE STUDY: The aim of this study was to compare two different in vitro models
      simulating the digestibility of two RS containing preparations. METHODS: The
      substrates, high amylose maize (HAM) containing RS type 2, and retrograded long
      chain tapioca maltodextrins (RTmd) containing RS type 3 were in vitro digested
      using a batch and a dynamic model, respectively. Both preparations were
      characterized before and after digestion by using X-Ray and DSC, and by measuring
      their total starch, RS and protein contents. RESULTS: Using both digestion
      models, 60-61 g/100 g of RTmd turned out to be indigestible, which is very well
      in accordance with 59 g/100 g found in vivo after feeding RTmd to ileostomy
      patients. In contrast, dynamic and batch in vitro digestion experiments using HAM
      as a substrate led to 58 g/100 g and 66 g/100 g RS recovery. The degradability of
      HAM is more affected by differences in experimental parameters compared to RTmd.
      The main variations between the two in vitro digestion methods are the enzyme
      preparations used, incubation times and mechanical stress exerted on the
      substrate. However, for both preparations dynamically digested fractions led to
      lower amounts of analytically RS and a lower crystallinity. CONCLUSIONS: The two
      in vitro digestion methods used attacked the starch molecules differently, which
      influenced starch digestibility of HAM but not of RTmd.

PMID- 17036262
TI  - Diet supplementation for 5 weeks with polyphenol-rich cereals improves several
      functions and the redox state of mouse leucocytes.
AB  - BACKGROUND: Cereals naturally contain a great variety of polyphenols, which exert
      a wide range of physiological effects both in vitro and in vivo. Many of their
      protective effects, including an improvement of the function and redox state of
      immune cells in unhealthy or aged subjects come from their properties as powerful
      antioxidant compounds. However, whether cereal-based dietary supplementation
      positively affects the immune function and cellular redox state of healthy
      subjects remains unclear. AIM OF THE STUDY: To investigate the effects of
      supplementation (20% wt/wt) for 5 weeks with four different cereal fractions on
      healthy mice. METHODS: Several parameters of function and redox state of
      peritoneal leukocytes were measured. The cereals, named B (wheat germ), C
      (buckwheat flour), D (fine rice bran) and E (wheat middlings) contained different
      amounts of gallic acid, p-hydroxybenzoic acid, vanillic acid, sinapic acid, p
      coumaric acid, ferulic acid, quercetin, catechin, rutin and oryzanol as major
      polyphenols. RESULTS: In general, all cereal fractions caused an improvement of
      the leukocyte parameters studied such as chemotaxis capacity, microbicidal
      activity, lymphoproliferative response to mitogens, interleukin-2 (IL-2) and
      tumor necrosis factor (TNFalpha) release, as well as oxidized glutathione (GSSG),
      GSSG/GSH ratio, catalase (CAT) activity and lipid oxidative damage. We observed
      similar effects among the cereal fractions. CONCLUSIONS: The results suggest that
      some of these effects may due, at least partially, to the antioxidant activity of
      the polyphenols naturally present in cereals. Since an appropriate function of
      the leukocytes has been proposed as marker of the health state, a short-term
      intake of cereals seems to be sufficient to exert a benefit in the health of the
      general population. However, further studies are needed to assess the optimal
      doses and to find out which active polyphenols are able to mediate the observed
      physiological effects before recommending their regular consumption.

PMID- 17036263
TI  - Stigma and discrimination towards people with schizophrenia and their family
      members. A qualitative study with focus groups.
AB  - BACKGROUND: There is a scarcity of data regarding the actual stigma and
      discrimination experienced by schizophrenic patients and their relatives. Those
      experiences can vary significantly depending on the specific social group
      involved. We have explored such phenomena in our culture with a qualitative
      technique. METHODS: We developed a qualitative study with focus groups of
      clinically stable schizophrenic outpatients (N = 18) and relatives (N = 26).
      Three groups were performed in each sample. RESULTS: Six categories of stigma and
      discrimination experiences were extracted from the patients' data: Mental illness
      vs. Lack of will, Prejudice related to dangerousness, Over-protection
      infantilization, Daily social discrimination, Discrimination in health care,
      Descendants, Avoidance-social isolation. Data from relatives were divided into
      three sets: discrimination towards the patients witnessed by relatives,
      discrimination suffered by the relatives themselves and discrimination exerted by
      the relatives on the patients. CONCLUSIONS: Patients and relatives describe a
      great variety of stigma and discrimination experiences in all areas of life,
      including health care. Isolation and avoidance are common reactions to those
      experiences. Publicizing these stigma and discrimination experiences could help
      to reduce stigmatizing attitudes in society and result in healthier reactions
      from patients, favoring a better course of the illness.

PMID- 17036264
TI  - Regional differences in psychiatric disorders in Chile.
AB  - BACKGROUND: Psychiatric epidemiological surveys in developing countries are rare
      and are frequently conducted in regions that are not necessarily representative
      of the entire country. In addition, in large countries with dispersed populations
      national rates may have low value for estimating the need for mental health
      services and programs. METHODS: The Chile Psychiatric Prevalence Study using the
      Composite International Diagnostic Interview was conducted in four distinct
      regions of the country on a stratified random sample of 2,978 people. Lifetime
      and 12-month prevalence and service utilization rates were estimated. RESULTS:
      Significant differences in the rates of major depressive disorder, substance
      abuse disorders, non-affective psychosis, and service utilization were found
      across the regions. The differential prevalence rates could not be accounted by
      socio-demographic differences between sites. CONCLUSIONS: Regional differences
      across countries may exist that have both implications for prevalence rates and
      service utilization. Planning mental health services for population centers that
      span wide geographical areas based on studies conducted in a single region may be
      misleading, and may result in areas with high need being underserved.

PMID- 17036265
TI  - Help-seeking pathways in early psychosis.
AB  - INTRODUCTION: Understanding the help-seeking pathways of patients with a putative
      risk of developing psychosis helps improving development of specialised care
      services. This study aimed at obtaining information about: type of health
      professionals contacted by patients at putative risk for psychosis on their help
      seeking pathways; number of contacts; type of symptoms leading to contacts with
      health professionals; interval between initial contact and referral to a
      specialised outpatient service. METHOD: The help-seeking pathways were assessed
      as part of a prospective study in 104 patients with suspected at-risk states for
      psychosis. RESULTS: The mean number of contacts prior to referral was 2.38.
      Patients with psychotic symptoms more often contacted mental health
      professionals, whereas patients with insidious and more unspecific features more
      frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been
      found to under-identify the insidious features of emerging psychosis (Simon et
      al. (2005) Br J Psychiatry 187:274-281). The fact that they were most often
      contacted by patients with exactly these features calls for focussed and
      specialised help for primary care physicians. Thus, delays along the help-seeking
      pathways may be shortened. This may be of particular relevance for patients with
      the deficit syndrome of schizophrenia.

PMID- 17036267
TI  - [Manifestation of diffuse proliferative lupus nephritis in a patient treated with
      long-term mycophenolate mofetil].
AB  - HISTORY AND ADMISSION FINDINGS: A now 34-year old female patient with long
      standing systemic lupus erythematosus (SLE) had successfully been treated with
      mycophenolate mofetil (MMF) because of former pleuropericardial and pulmonal
      lupus manifestations when she was admitted with edema for the first time.
      INVESTIGATIONS: Laboratory investigations of urine and blood showed findings
      compatible with lupus nephritis. Kidney biopsy revealed lupus nephritis type IV.
      TREATMENT AND COURSE: Despite the initiation of cyclophosphamide bolus and
      corticosteroid therapy, the kidney function and renal hypertension worsened and
      the patient developed cerebral manifestations. Finally, synchronization of
      plasmapheresis with subsequent pulse cyclophosphamide led to remission of SLE.
      CONCLUSION: Although MMF is a promising innovative agent for induction and
      maintenance therapy of lupus nephritis that can be used instead of
      cyclophosphamide, there may be cases like the one reported here, in which MMF
      cannot prevent lupus flares in first manifestation of severe renal disease.

PMID- 17036268
TI  - [Churg-Strauss syndrome--recent developments in diagnosis and treatment].

PMID- 17036270
TI  - [Biologicals in the treatment of rheumatic diseases].

PMID- 17036271
TI  - [Intra-articular injections of corticosteroids--pro].

PMID- 17036272
TI  - [Intra-articular injections of corticosteroids--contra].

PMID- 17036273
TI  - [Regulatory T cells in rheumatic diseases].

PMID- 17036274
TI  - [Do we need in-patient rheumatology?].

PMID- 17036276
TI  - [Therapy of hypertension in the elderly].

PMID- 17036278
TI  - [Physician-assisted suicide -- ethical, legal and clinical aspects].

PMID- 17036279
TI  - [Cardioverter-defibrillator (ICD) and resynchronization in every patient with
      cardiac failure].

PMID- 17036281
TI  - Intake of 13C-4 creatine enables simultaneous assessment of creatine and
      phosphocreatine pools in human skeletal muscle by 13C MR spectroscopy.
AB  - The feasibility of a novel method for the noninvasive and local assessment of
      creatine (Cr) and phosphocreatine (PCr) dynamics in human skeletal muscle based
      on (13)C magnetic resonance (MR) spectroscopy is presented. A high dose of Cr,
      labeled at the guanidino C-4 position with (13)C 11% enrichment, was administered
      orally to a human subject for 5 days. Using a surface coil, (13)C MR spectra of
      the lower leg were acquired on a 1.5T MR system at regular time intervals during
      and after Cr supplementation. An almost twofold increase in the intensities of
      the resolved PCr and Cr (13)C-4 signals was observed during this period. The slow
      decrease in these signals to normal values after supplementation reflects the
      slow daily turnover of Cr. The PCr/Cr ratio did not appear to change over the
      whole measurement period. During exercise of the leg, reversible changes in PCr
      and Cr signals were observed, reflecting conversion by the Cr kinase reaction.

PMID- 17036282
TI  - Water exchange across the erythrocyte plasma membrane studied by HR-MAS NMR
      spectroscopy.
AB  - Water exchange across the plasma membrane of erythrocytes (red blood cells
      (RBCs)) was studied by means of high-resolution magic angle spinning (HR-MAS) NMR
      spectroscopy. Under HR-MAS conditions, the centrifugal force causes the splitting
      of RBC suspensions into a two-phase system composed of a central core of cell
      free water and an outer layer of tightly packed cells. Water belonging to each of
      these phases gives rise to two separated resonances. Chemical exchange between
      them is not detectable on the chemical shift or saturation transfer (ST) NMR time
      scale because of the physical separation between the phases. When the RBCs are
      dispersed and immobilized within a matrix made of cross-linked albumin, the
      splitting into a two-phase system is prevented and a single exchange-averaged
      peak for water is detected in (1)H HR-MAS NMR spectra. The lineshape of this peak
      is dependent on transmembrane exchange kinetics, since MAS averages out all the
      anisotropic magnetic interactions that are responsible for additional line
      broadening under conventional liquid conditions. Line-shape analysis according to
      a two-site exchange model yielded a residence lifetime on the order of about 10
      ms (at 37 degrees C) for a water molecule within the intracellular compartment,
      which is not too far from the generally accepted value of 9.6-14.8 ms.

PMID- 17036283
TI  - Magnetic resonance elastography of the lung: technical feasibility.
AB  - Magnetic resonance elastography (MRE) is a phase-contrast technique that can
      spatially map shear stiffness within tissue-like materials. To date, however, MRE
      of the lung has been too technically challenging-primarily because of signal-to
      noise ratio (SNR) limitations and phase instability. We describe an approach in
      which shear wave propagation is not encoded into the phase of the MR signal of a
      material, but rather from the signal arising from a polarized noble gas
      encapsulated within. To determine the feasibility of the approach, three
      experiments were performed. First, to establish whether shear wave propagation
      within lung parenchyma can be visualized with phase-contrast MR techniques, MRE
      was performed on excised porcine lungs inflated with room air. Second, a phantom
      consisting of open-cell foam filled with thermally polarized (3)He gas was imaged
      with MRE to determine whether shear wave propagation can be encoded by the gas.
      Third, preliminary evidence of the feasibility of MRE in vivo was obtained by
      using a longitudinal driver on the chest of a normal volunteer to generate shear
      waves in the lung. The results suggest that MRE in combination with
      hyperpolarized noble gases is potentially useful for noninvasively assessing the
      regional elastic properties of lung parenchyma, and merits further investigation.

PMID- 17036284
TI  - On the origin of apparent low tissue signals in balanced SSFP.
AB  - Balanced steady-state free precession (bSSFP) has become increasingly important
      in clinical applications. Its signal properties have been investigated over
      several years by many groups, and various critical factors for bSSFP signal
      intensity and stability, such as off-resonances, flow, and eddy currents, have
      been identified. It is generally accepted that bSSFP signal intensity is a
      function of relaxation times, excitation angles, and spin densities only. While
      this is true for simple phantoms, it appears that signals from tissues are
      significantly less intense than predicted by theory. This work demonstrates that
      the molecular origin of this apparent signal reduction is due to on-resonance
      magnetization transfer (MT). High flip angles in combination with very short
      repetition times (TRs), as commonly used for bSSFP, lead to a considerable
      saturation in the fraction of macromolecular (MM) pool protons. As a result,
      bSSFP signal is strongly attenuated by up to a factor of 2 in the human brain
      compared to the signal expected from theory.

PMID- 17036285
TI  - Minimally invasive skin rejuvenation with Erbium: YAG laser used in thermal mode.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the efficacy and safety of a thermal mode
      Erbium:YAG laser several in-vivo morphological as well as clinical changes were
      monitored in a multi-center investigation. STUDY DESIGN/MATERIALS AND METHODS: An
      Erbium:YAG laser was used at a thermal mode with sub-ablative fluences of 2.1 and
      3.1 J/cm(2) with parallel air cooling to treat either periorbital, perioral
      rhytides or patients with post-traumatic or acne scars. Two treatments were
      applied 2 months apart, with follow-up at 1, 3, 6, and 12 months post-treatment.
      Photographs were taken before and at each follow-up visit and evaluated by three
      blinded independent reviewers. Histology and immunohistochemistry for pro
      collagen expression were investigated. Optical coherence tomography (OCT) was
      performed before, and at 4, 14, and 28 days after single pass treatment with
      Erbium:YAG thermal pulses. RESULTS: The improvement of rhytides at 1-3 months
      follow-up was graded as excellent in 19%, good in 19%, fair in 31%, and no
      improvement in 31%. At the 6- to 12-month follow-up, the improvement was
      excellent in 40%, good in 40%, fair in 20%, and no improvement in 0%. The
      improvement of scars at 3-6 months follow-up was graded as excellent in 50%, good
      in 25%, fair in 25%, and no improvement in 0%. Intra- and post-operative
      discomfort was described as mild by the patients. OCT, histological sections and
      immunohistochemistry demonstrated production of new collagen bundles.
      CONCLUSIONS: Thermal Erbium:YAG pulses can induce collagen neogenesis, as proved
      by temperature elevation and morphological changes in the upper dermis. This
      leads clinically to visible and long lasting reduction of wrinkles and scars
      after applying multiple passes with minimal side-effects.

PMID- 17036286
TI  - Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness.
AB  - OBJECTIVE: The fukutin gene (FKTN) is the causative gene for Fukuyama-type
      congenital muscular dystrophy, characterized by rather homogeneous clinical
      features of severe muscle wasting and hypotonia from early infancy with mental
      retardation. In contrast with the severe dystrophic involvement of skeletal
      muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular
      dystrophy is one of the disorders associated with glycosylation defects of alpha
      dystroglycan, an indispensable molecule for intra-extra cell membrane linkage.
      METHODS: Protein and functional analyses of alpha-dystroglycan and mutation
      screening of FKTN and other associated genes were performed. RESULTS:
      Surprisingly, we identified six patients in four families showing dilated
      cardiomyopathy with no or minimal limb girdle muscle involvement and normal
      intelligence, associated with a compound heterozygous FKTN mutation. One patient
      died by rapid progressive dilated cardiomyopathy at 12 years old, and the other
      patient received cardiac implantation at 18 years old. Skeletal muscles from the
      patients showed minimal dystrophic features but have altered glycosylation of
      alpha-dystroglycan and reduced laminin binding ability. One cardiac muscle that
      underwent biopsy showed altered glycosylation of alpha-dystroglycan similar to
      that observed in a Fukuyama-type congenital muscular dystrophy patient.
      INTERPRETATION: FKTN mutations could cause much wider spectrum of clinical
      features than previously perceived, including familial dilated cardiomyopathy and
      mildest limb girdle muscular dystrophy.

PMID- 17036287
TI  - CLN3P, the Batten's disease protein, is a novel palmitoyl-protein Delta-9
      desaturase.
AB  - OBJECTIVE: Batten's disease, one of the most common recessively inherited,
      untreatable, neurodegenerative diseases of humans, is characterized by
      progressive neuronal loss and intraneuronal proteolipid storage. Although the
      gene for the disorder was cloned more than a decade ago, the function of the
      encoded protein, CLN3P, has not been defined thus far. METHODS: Sequence analysis
      using the Pfam server identified a low stringency match to a fatty acid
      desaturase domain in the N-terminal sequence of CLN3P. We developed a fatty acid
      desaturase assay based on measurement of desaturase products by gas
      chromatography/mass spectrometry. RESULTS: We show that CLN3P is a novel
      palmitoyl-protein Delta-9 desaturase, which converts membrane-associated
      palmitoylated proteins to their respective palmitoleated derivatives. We have
      further demonstrated that this palmitoyl-protein Delta-9 desaturase activity is
      deficient in cln3(-/-) mouse pancreas and is completely ablated in neuroblastoma
      cells by RNA inhibition. INTERPRETATION: We propose that palmitoyl-protein
      desaturation defines a new mechanism of proteolipid modification, and that
      deficiency of this process leads to the signs and symptoms of Batten's disease.

PMID- 17036288
TI  - Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C
      NMR of urinary menthol glucuronide.
AB  - Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject
      following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose.
      Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high
      signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin
      coupled multiplet components within each (13)C resonance by (13)C NMR. The [U
      (13)C]glucuronide isotopomer derived via direct pathway conversion of [U
      (13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and
      [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway
      metabolism of [U-(13)C]glucose. In a second study, a group of four overnight
      fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint
      oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min
      constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment
      of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C
      isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6%
      +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide
      enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic
      UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP),
      and the Cori cycle accounted for at least 32% +/- 10% of GP.

PMID- 17036289
TI  - Parallel RF transmission with eight channels at 3 Tesla.
AB  - Spatially selective RF waveforms were designed and demonstrated for parallel
      excitation with a dedicated eight-coil transmit array on a modified 3T human MRI
      scanner. Measured excitation profiles of individual coils in the array were used
      in a low-flip-angle pulse design to achieve desired spatial target profiles with
      two- (2D) and three-dimensional (3D) k-space excitation with simultaneous
      transmission of RF on eight channels. The 2D pulse excited a high-resolution
      spatial pattern in-plane, while the 3D trajectory produced high-quality slice
      selection with a uniform in-plane excitation despite the highly nonuniform
      individual spatial profiles of the coil array. The multichannel parallel RF
      excitation was used to accelerate the 2D excitation by factors of 2-8, and
      experimental results were in excellent agreement with simulations based on the
      measured coil maps. Parallel RF transmission may become critical for robust and
      routine human studies at very high field strengths where B(1) inhomogeneity is
      commonly severe.

PMID- 17036291
TI  - Electrochemical switching of the cubic nonlinear optical properties of an
      aryldiethynyl-linked heterobimetallic complex between three distinct states.

PMID- 17036290
TI  - Fluorescence visualization of newly synthesized proteins in mammalian cells.

PMID- 17036292
TI  - A virus spotlighted by an autonomous DNA machine.

PMID- 17036293
TI  - Total synthesis of paliurine F.

PMID- 17036294
TI  - Dynamically self-assembling metalloenzyme models based on calixarenes.

PMID- 17036296
TI  - Chemisorption-induced double hydrogen bonding, self-assembly, and
      stereoselection.

PMID- 17036295
TI  - Substrate mimicry in an activity-based probe that targets the nitrilase family of
      enzymes.

PMID- 17036297
TI  - Formation and stability of G-quadruplexes self-assembled from guanine-rich
      strands.
AB  - Electrospray ionization mass spectrometry (ESI-MS) was utilized to investigate
      the formation and stability of G-quadruplexes. For the 15 6-nt oligonucleotides
      tested, ESI-MS indicated that formation of a parallel tetramer quadruplex
      requires at least four continuous guanines in the 6-nt sequence. In addition, the
      G-rich strands prefer to employ "self-association" in the formation of the G
      quadruplex rather than hybridized integration, and the thermodynamic-stability
      order of these three G-quadruplexes is Q(2)>Q(1)>Q(3).

PMID- 17036298
TI  - Synthesis and characteristics of a nonaggregating
      tris(tetrathiafulvaleno)dodecadehydro[18]annulene.
AB  - A new tris(tetrathiafulvaleno)dodecadehydro[18]annulene with six peripheral n
      hexyl substituents was prepared by oxidative Glaser-Hay cyclization of a
      corresponding diethynylated tetrathiafulvalene (TTF) precursor. The electronic
      properties of the neutral and oxidized species were studied by both UV/Vis
      absorption spectroscopy and electrochemistry. From these studies, it transpires
      that the strongly violet-colored macrocycle does not aggregate in solution to any
      significant degree, which was confirmed by (1)H NMR spectroscopy. This reluctance
      towards aggregation contrasts that observed for related TTF-annulenes containing
      other peripheral substitutents. Oxidation of the TTF-annulene occurs in two three
      electron steps as inferred from both the peak amplitudes and the
      spectroelectrochemical study. We find that the tris(TTF)-fused
      dehydro[18]annulene is more difficult to oxidize (by +0.20 V) than the silyl
      protected diethynylated mono-TTF precursor. In contrast, the first vertical
      ionization energy calculated at the B3 LYP/6-311+G(2d,p) level for the parent
      tris(TTF)-fused dehydro[18]annulene devoid of peripheral hexyl substituents is in
      fact lower (by 0.44 eV). Moreover, the surface morphology of 1 d drop-cast on a
      mica substrate was investigated by atomic force microscopy (AFM). Crystalline
      domains with slightly different orientations were observed. The thickness of
      individual layers seen in the crystalline domains and the thickness of a
      monolayer obtained from a very dilute solution were determined to 1.8-1.9 nm.
      This thickness corresponds to the diameter of the macrocycle and the layers seen
      in the film are apparently formed when the molecules stack in the horizontal
      direction relative to the substrate.

PMID- 17036299
TI  - Room-temperature Au(I)-catalyzed C-C bond formation through a tandem Friedel
      Crafts-type addition/carbocyclization reaction.

PMID- 17036300
TI  - Real-time interactive MRI-guided cardiac surgery: aortic valve replacement using
      a direct apical approach.
AB  - Minimally invasive cardiac surgery requires arresting and emptying of the heart,
      which compromises visualization of the surgical field. In this feasibility study
      a novel surgical procedure is demonstrated in which real-time MRI is used to
      guide the placement of a prosthetic aortic valve in the beating heart via direct
      apical access in eight porcine hearts. A clinical stentless bioprosthetic valve
      affixed to a platinum stent was compressed onto a balloon-tipped catheter. This
      was fed through a 15-18-mm delivery port inserted into the left ventricular (LV)
      apex via a minimally invasive subxyphoid incision. Using interactive real-time
      MRI, the surgeon implanted the prosthetic valve in the correct location at the
      aortic annulus within 90 s. In four of the animals immediately after
      implantation, ventricular function, blood flow through the valve, and myocardial
      perfusion were evaluated with MRI. MRI-guided beating-heart surgery may provide
      patients with a less morbid and more durable solution to structural heart
      disease.

PMID- 17036301
TI  - Experimentally-derived functional form for a population-averaged high-temporal
      resolution arterial input function for dynamic contrast-enhanced MRI.
AB  - Rapid T(1)-weighted 3D spoiled gradient-echo (GRE) data sets were acquired in the
      abdomen of 23 cancer patients during a total of 113 separate visits to allow
      dynamic contrast-enhanced MRI (DCE-MRI) analysis of tumor microvasculature. The
      arterial input function (AIF) was measured in each patient at each visit using an
      automated AIF extraction method following a standardized bolus administration of
      gadodiamide. The AIFs for each patient were combined to obtain a mean AIF that is
      representative for any individual. The functional form of this general AIF may be
      useful for studies in which AIF measurements are not possible. Improvements in
      the reproducibility of DCE-MRI model parameters (K(trans), v(e), and v(p)) were
      observed when this new, high-temporal-resolution population AIF was used,
      indicating the potential for increased sensitivity to therapy-induced change.

PMID- 17036303
TI  - Selective suppression of artifact-generating echoes in cine DENSE using through
      plane dephasing.
AB  - In displacement-encoded imaging with stimulated echoes (DENSE), tissue
      displacement is encoded in the phase of the stimulated echo. However, three
      echoes generally contribute to the acquired signal (the stimulated echo, the
      complex conjugate of the stimulated echo, and an echo due to T(1) relaxation). It
      is usually desirable to suppress all except the stimulated echo, since otherwise
      the additional echoes will cause displacement measurement errors. Ideally,
      suppression of the artifact-generating echoes would be independent of time, T(1),
      and displacement-encoding frequency, and would not require additional
      acquisitions. In this study through-plane gradients were used to selectively
      dephase artifact-generating echoes without causing significant signal loss of the
      stimulated echo. A cine DENSE sequence was modified to include dephasing
      gradients and perform complementary spatial modulation of magnetization (CSPAMM).
      For single-acquisition cine DENSE using dephasing alone, artifact suppression was
      similar to CSPAMM with two acquisitions. The use of dephasing with CSPAMM
      required two acquisitions, but demonstrated greater artifact suppression than
      CSPAMM alone or dephasing alone.

PMID- 17036302
TI  - Feasibility of in vivo identification of endogenous ferritin with positive
      contrast MRI in rabbit carotid crush injury using GRASP.
AB  - In vivo markers that allow for detection of ferritin within atheromatous plaque
      may be useful for identifying iron-catalyzed hydroxyl-radical formation and
      subsequent lipid peroxidation. Recently, a positive contrast MR technique-
      GRadient echo Acquisition for Superparamagnetic particles/suscePtibility (GRASP)-
      was used to identify the presence of magnetic entities in phantom models. The aim
      of the current study was to determine the feasibility of using GRASP in
      conjunction with conventional T(2) (*)-weighted (T(2) (*)W) gradient-echo (GRE)
      sequences for identifying ferritin/hemosiderin deposition using in vitro and in
      vivo models of thrombus. In vitro thrombi were prepared by incubating blood with
      ferritin. MRI was performed using conventional GRE sequences and GRASP. The
      results indicate that GRASP was able to verify ferritin deposition in in vitro
      thrombi. In vivo thrombi were created using a crush injury model in rabbits. The
      signal enhancement obtained using conventional GRE sequences and GRASP was
      compared with the location of iron deposition by histology. In all of the animals
      the GRASP signal correlated with signal loss by conventional GRE, and
      ferritin/hemosiderin deposition by histology. GRASP sequences in combination with
      conventional GRE sequences may be used to detect the presence of ferritin
      deposition in in vitro thrombi and in vivo crush-injured rabbit carotid arteries.

PMID- 17036304
TI  - Can MM-PBSA calculations predict the specificities of protein kinase inhibitors?
AB  - An application of the molecular mechanics Poisson-Boltzmann surface area (MM
      PBSA) protocol to the prediction of protein kinase inhibitor selectivity is
      presented. Six different inhibitors are placed in equivalent orientations in each
      of six different receptors. Fully solvated molecular dynamics is then run for 1
      ns on each of the 36 complexes, and the resulting trajectories scored, using the
      implicit solvent model. The results show some correlation with experimentally
      determined specificities; anomalies may be attributed to a variety of causes,
      including difficulties in quantifying induced fit penalties and variabilities in
      normal modes calculations. Decomposing interaction energies on a per-residue
      basis yields more useful insights into the natures of the binding modes and
      suggests that the real value of such calculations lies in understanding
      interactions rather than outright prediction.

PMID- 17036305
TI  - Expression patterns of ubiquitin, heat shock protein 70, alpha-actin and beta
      actin over the molt cycle in the abdominal muscle of marine shrimp Litopenaeus
      vannamei.
AB  - Crustacean muscle growth is discontinuous due to molt cycle. To characterize molt
      related gene expression patterns, we studied the mRNA levels of molecular
      chaperone-ubiquitin and heat shock protein 70 (Hsp 70) in comparison with muscle
      protein alpha-actin and beta-actin in marine shrimp Litopenaeus vannamei. Total
      RNA from abdominal muscle was isolated from 3-month-old animals in six different
      molt stages. The mRNA levels of target genes were detected by reverse
      transcriptase-multiplex PCR and expressed as the ratio to elongation factor
      1alpha. Ubiquitin mRNA levels were relatively steady over all stages of the molt
      cycle. Hsp70 levels were not detectable in early postmolt and late premolt
      stages, but showed a progressive increase from late postmolt to intermolt stages.
      Expression levels of alpha-actin gene were lower during postmolt, reached a
      plateau in intermolt and remained relatively high in premolt stage. Levels of
      beta-actin increased progressively from postmolt to intermolt, reaching a maximum
      value in premolt. Therefore, the mRNAs encoding for ubiquitin and Hsp 70 in
      abdominal muscle did not increase significantly in premolt stages, which is
      typically associated with claw muscle degradation. Muscle structural alpha-actin
      and cytoskeletal beta-actin were increased during intermolt and premolt stages,
      suggesting high muscle growth during these stages in the abdominal muscle of the
      L. vannamei.

PMID- 17036306
TI  - Biosensor-based characterization of serum antibodies during development of an
      anti-IgE immunotherapeutic against allergy and asthma.
AB  - Antibody responses, induced in Cynomolgus monkey by recombinant IgE-derived
      immunotherapeutic protein against atopic allergies and asthma, were characterized
      using label-free, real-time protein interaction analysis. The effects of two
      different immunotherapeutic proteins were compared. Active concentrations of
      specific anti-IgE antibodies formed were determined in sera sampled at multiple
      time points, using conditions of total mass transport limitation that were proved
      to exist on the sensor surface. These concentrations varied from about 0.4 to 35
      microg/ml among the monkeys and throughout the immunization period. Based on
      these concentrations, the rate and affinity constants for the binding of antibody
      populations to the antigen could be determined. The apparent equilibrium
      dissociation constant decreased during the immunization period, for all the
      monkeys, by a factor between 6 and 50, ending at values from approximately 2 x
      10(-9) to approximately 2 x 10(-11) M among the animals. This affinity maturation
      was attributable to the changes in both rate constants, although the magnitude of
      the contribution of each constant depended partly on specimen, but primarily on
      the immunotherapeutic used. The immunotherapeutic proteins examined showed
      excellent immunogenic properties, providing the basis for a new and effective
      treatment for allergy and asthma.

PMID- 17036307
TI  - The muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet):
      surveillance methodology.
AB  - BACKGROUND: This report focuses on the common protocol developed by the Muscular
      Dystrophy Surveillance Tracking and Research Network (MD STARnet) for population
      based surveillance of Duchenne and Becker muscular dystrophy (DBMD) among 4
      states (Arizona, Colorado, Iowa, and New York). METHODS: The network sites have
      developed a case definition and surveillance protocol along with software
      applications for medical record abstraction, clinical review, and pooled data.
      Neuromuscular specialists at each site review the pooled data to determine if a
      case meets the case criteria. Sources of potential cases of DBMD include
      neuromuscular specialty clinics, service sites for children with special
      healthcare needs, and hospital discharge databases. Each site also adheres to a
      common information assurance protocol. RESULTS: A population-based surveillance
      system for DBMD was created and implemented in participating states. CONCLUSIONS:
      The development and implementation of the population-based system will allow for
      the collection of information that is intended to provide a greater understanding
      of DBMD prevalence and health outcomes.

PMID- 17036308
TI  - Incorporating genetic analyses into birth defects cluster investigations:
      strategies for identifying candidate genes.
AB  - BACKGROUND: Incorporating genetic analyses into birth defect cluster
      investigations may increase understanding of both genetic and environmental risk
      factors for the defect. Current constraints of most birth defect cluster
      investigations make candidate gene selection the most feasible approach. Here, we
      describe strategies for choosing candidate genes for such investigations, which
      will also be applicable to more general gene-environment studies. METHODS: We
      reviewed publicly available web-based resources for selection of candidate genes
      and identification of risk factors, as well as publications on different
      strategies for candidate gene selection. RESULTS: Candidate gene selection
      requires consideration of available gene-disease databases, previous
      epidemiological studies, animal model research, linkage and expression studies,
      and other resources. We describe general considerations for utilizing available
      resources, as well as provide an example of a search for candidate genes related
      to gastroschisis. CONCLUSIONS: Available web resources could facilitate selection
      of candidate genes, but selection of optimal candidates will still require a
      strong understanding of genetics and the pathogenesis of the defect, as well as
      careful consideration of previous epidemiological studies.

PMID- 17036309
TI  - Parietal bone agenesis with gracile bones and splenic hypoplasia/aplasia: clinico
      pathologic report and differential diagnosis with review of cranio-gracile bone
      syndromes, "osteocraniostenosis" and Kleeblattschadel.
AB  - The findings in a newborn male with agenesis of parietal bones, gracile long
      bones, and hypoplasia of the spleen are presented. Although parietal agenesis is
      unique, the findings are compatible with 18 previously reported cases
      characterized by cranial hypomineralization, Kleeblatschadel, gracile bones, and
      splenic aplasia/hypoplasia, the nomenclature for which has been descriptive:
      gracile bone disorders, "osteocraniostenosis," "osteocraniosplenic syndrome." The
      term "osteocraniostenosis" may be inappropriate in that craniostenosis has been
      infrequently reported, a feature also of importance with respect to the
      pathogenesis of the Kleeblatschadel. The group likely reflects heterogeneous
      etiology and pathogenesis. Precedent, however, including animal models, justifies
      consideration of genetic aberrations, in particular, mutations in homeobox genes.
      (c) 2006 Wiley-Liss, Inc.

PMID- 17036310
TI  - Association between the NAT1 1095C > A polymorphism and homocysteine
      concentration.

PMID- 17036311
TI  - Atypical cases of Angelman syndrome.
AB  - Angelman syndrome (AS) is a profound disorder notable for mental retardation and
      severe language deficits that results from lack of function of the maternally
      inherited copy of the UBE3A gene. Chromosome deletions of 15q11q13, paternal
      uniparental disomy (UPD), UBE3A gene mutations, and imprinting center defects are
      all commonly recognized mechanisms that disrupt the function of the maternal copy
      of the UBE3A gene. We report here two patients with different atypical etiologies
      of AS. The first patient is a 3-year-old boy with global developmental delay,
      severe speech deficits, seizures, and very happy disposition. Southern blot
      analysis for the maternal and paternal chromosome 15 methylation products showed
      a mosaic methylation pattern, suggesting an imprinting center defect. The second
      patient is a 4(1/2)-year-old boy with global developmental delay, no expressive
      language, microcephaly, seizures, and ataxic gait. Array-based comparative
      genomic hybridization (CGH) demonstrated a loss in copy number for two
      overlapping clones encompassing the UBE3A gene, indicating a partial deletion
      within UBE3A. His mother, who was adopted, had an identical pattern, suggesting
      that her deletion was probably on her paternally imprinted allele. These patients
      illustrate the expanding spectrum of molecular findings in AS, reinforce the need
      to maintain suspicion when clinical features suggest AS but initial testing is
      normal, and show the power of CGH as a tool to uncover partial UBE3A deletions.

PMID- 17036312
TI  - Attitudes of genetic counselors towards expanding newborn screening and offering
      predictive genetic testing to children.
AB  - There is movement to expand newborn screening (NBS) to include conditions that
      challenge the traditional public health screening criteria. Little is known about
      the attitudes of genetic counselors towards expanding NBS and offering predictive
      genetic tests to children. For our study genetic counselors completed an internet
      survey posted on the National Society of Genetic Counselors Listserv regarding
      five conditions: cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), glucose
      6-phosphate dehydrogenase deficiency (G6PD), fragile X (FraX), and type 1
      diabetes (T1D). The survey addressed attitudes towards: (1) testing high-risk
      infants; (2) mandatory NBS; (3) population screening beyond the newborn period;
      and (4) testing one's own child. Two hundred sixty-seven usable surveys were
      received. Over two-thirds of respondents supported testing high-risk infants for
      all conditions except T1D (22%). CF was the only condition for which there was
      majority support for both mandatory NBS (56%) and later population screening
      (60%). For all other conditions, later population screening was preferred over
      NBS (P <or= 0.01). Genetic counselors were most likely to test their own child
      for CF (46%) and least likely to test their own child for T1D (6%). For each
      condition, genetic counselors were more likely to support NBS if they chose to
      screen their own newborn (P < 0.001). Attitudes towards NBS were not influenced
      by year of graduation or professional experience. We can conclude that genetic
      counselors are supportive of targeted testing of high-risk infants. They prefer
      voluntary population screening with consent to mandatory NBS for conditions that
      challenge Wilson and Jungner criteria. Their support for NBS correlates with
      their interest in testing their own children and not with professional
      experience.

PMID- 17036313
TI  - V37I connexin 26 allele in patients with sensorineural hearing loss: evidence of
      its pathogenicity.
AB  - Sensorineural hearing loss (SNHL) is the most common inherited sensory disorder,
      reported in 1-3 of every 1,000 births. It has been estimated that 50% of all
      cases of prelingual SNHL are genetically determined. There is tremendous genetic
      heterogeneity, with multiple dominant and recessive loci. Mutations of the gap
      junction beta-2 gene (GJB2) emerge as a leading cause of autosomal recessive non
      syndromic SNHL. Over 90 sequence alterations have been reported, the
      pathogenicity of some of them being unknown or unclear. The status of the V37I
      allele of connexin 26 (GJB2 amino acid product) with regards to its association
      with SNHL has been controversial. This study examines the pathogenicity of V37I
      by comparing the frequency of this allele in 40 patients with SNHL of Chinese and
      Caucasian descent with the frequency of the allele in 100 anonymized, ethnically
      matched controls. The V37I allele was identified in 43.75 and 11.5% of the
      patient and control alleles of Chinese ethnicity, respectively, but was not found
      in either Caucasian cohort. We also compiled the audiograms of 15 individuals
      with SNHL homozygous for the V37I allele, and showed that these individuals
      present with a mild to moderate SNHL. These results indicate that (1) the V37I
      allele is common in individuals of Chinese descent but rarely present in
      individuals of Caucasian decent; and (2) the V37I allele is pathogenic, but
      produces milder hearing loss compared to nonsense mutations of connexin 26 such
      as the 35delG mutation.

PMID- 17036314
TI  - FISH and array-CGH analysis of a complex chromosome 3 aberration suggests that
      loss of CNTN4 and CRBN contributes to mental retardation in 3pter deletions.
AB  - Imbalances of 3p telomeric sequences cause 3p- and trisomy 3p syndrome,
      respectively, showing distinct, but also shared clinical features. No causative
      genes have been identified in trisomy 3p patients, but for the 3p- syndrome,
      there is growing evidence that monosomy for one or more of four genes at 3pter,
      CHL1, CNTN4, CRBN, and MEGAP/srGAP3, may play a causative role. We describe here
      an analysis of a complex chromosome 3p aberration in a severely mentally retarded
      patient that revealed two adjacent segments with different copy number gains and
      a distal deletion. The deletion in this patient included the loci for CHL1,
      CNTN4, and CRBN, and narrowed the critical segment associated with the 3p-
      syndrome to 1.5 Mb, including the loci for CNTN4 and CRBN. We speculate that the
      deletion contributes more to this patient's phenotype than the gains that were
      observed. We suggest that 3p- syndrome associated features are primarily caused
      by loss of CNTN4 and CRBN, with loss of CHL1 probably having an additional
      detrimental effect on the cognitive functioning of the present patient.

PMID- 17036315
TI  - Daughter and her mildly affected father with Keipert syndrome.
AB  - A 10-year-old girl with characteristic features of Keipert syndrome (broad
      terminal phalanges, especially of the thumb and hallux, sensorineural deafness,
      unusual facial features, large head circumference, maxillary hypoplasia, hoarse
      voice) and her mildly affected father (broad terminal phalanges, especially of
      the thumb and hallux, large head circumference, maxillary hypoplasia, and hoarse
      voice) are presented. The girl is the first reported female with this rare
      syndrome to date, and the fact that she probably inherited the disease from her
      father suggests an autosomal dominant pattern of inheritance.

PMID- 17036316
TI  - The beta-delta-core of sarcoglycan is essential for deposition at the plasma
      membrane.
AB  - Mutations of any of the sarcoglycan complex subunits (alpha, beta, delta, and
      gamma) cause limb-girdle muscular dystrophy. Furthermore, individual mutations
      lead to a reduction or loss of all other members of the complex. In some cases of
      limb-girdle muscular dystrophies, however, residual sarcoglycan expression has
      been documented. Therefore, in this study we tested the hypothesis that formation
      of specific sarcoglycan subcomplexes is crucial for plasma membrane deposition.
      Using co-immunoprecipitation assays, we demonstrated that beta- and delta
      sarcoglycan interact with alpha-sarcoglycan and these two subunits must be co
      expressed for export from the endoplasmic reticulum. Advanced light-microscopic
      imaging techniques demonstrated that co-expression of beta-sarcoglycan and delta
      sarcoglycan is also responsible for delivery to and retention of sarcoglycan
      subcomplexes at the cell surface. These data suggest that formation of the beta
      delta-core may promote the export and deposition of sarcoglycan subcomplexes at
      the plasma membrane, and therefore identifies a mechanism for sarcoglycan
      transport.

PMID- 17036318
TI  - Deaths due to choking in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is the most common known syndromic cause of life
      threatening obesity, yet few studies have examined the causes of death in PWS.
      The objective of this study was to examine the contribution of choking leading to
      mortality in PWS. In 1999, a brief survey was made available from the Prader
      Willi Syndrome Association (USA) bereavement program, which documented
      demographic data and causes of death. Families were subsequently offered the
      opportunity to fill out a detailed questionnaire and additional forms to release
      medical records. Demographic information was available on 178 deceased
      individuals with PWS, and cause of death available on 152 individuals. Fifty-four
      families completed questionnaires. Of the deceased individuals with completed
      questionnaires, 34% reported a history of choking. Choking was listed by familial
      report as the cause of death in 12 (7.9%) of 152 subjects with an average age of
      24 years (range 3-52 years; median 22.5 years) at death from choking. Only two of
      these individuals were less than 8 years of age. The data suggest that risks
      associated with choking are different in the PWS population compared with others.
      Potential causes of increased choking in PWS include poor oral/motor
      coordination, poor gag reflex, hypotonia, hyperphagia, decreased mastication, and
      voracious feeding habits. We recommend implementation of preventive measures and
      education for families and group home care providers for all individuals with PWS
      including the Heimlich maneuver, supervised meals, better food preparation, and
      diet modification to avoid high-risk choking items.

PMID- 17036319
TI  - Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination
      therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231).
AB  - Some kinds of breast cancer cell lines, similar to several types of solid tumors,
      express epidermal growth factor receptor (EGFR). However, gefitinib, an EGFR
      tyrosine kinase inhibitor, is not effective for all these cell lines. Similarly,
      taxane is effective for many of the cell lines, although some, such as the
      multidrug-resistant MCF7/ADR cell line, show taxane-resistance. Here, we examined
      the growth inhibitory effect of combination treatment with gefitinib and taxane
      on the breast cancer cell lines MDA-MB-231 (EGFR-positive) and MCF7/ADR (EGFR-
      and HER2-positive). To estimate the combined effect, a Combination Index was
      calculated for each cell line. The combination of gefitinib and taxane showed a
      strong synergistic effect on MCF7/ADR cells, but an invitro additive-antagonistic
      effect on MDA-MB-231 cells. Similarly, the combination treatment showed a
      significantly increased tumor inhibitory effect on MCF7/ADR xenografts, but not
      on MDA-MB-231 xenografts. Regarding the mechanism of the synergistic effect,
      Western blotting analysis revealed that taxane activated the EGFR-Akt pathway in
      MCF7/ADR cells but not in MDA-MB-231. To determine the optimal sequential
      administration of gefitinib and taxane for MCF7/ADR cells, we used flow cytometry
      to analyze the cell cycle and apoptosis; finding that taxane treatment followed
      by gefitinib produced a higher rate of G2 arrest and apoptosis than gefitinib
      treatment followed by taxane. These results suggest gefitinib overcomes the drug
      resistance of these cells, thereby increasing the effects of taxane on MCF7/ADR
      cells. Further, activation of the EGFR-Akt pathway by taxane is related to this
      synergistic effect.

PMID- 17036321
TI  - An interferon-sensitive response element is involved in constitutive caspase-8
      gene expression in neuroblastoma cells.
AB  - We previously identified a 1.2 Kb DNA element (P-1161/+16), 5' to caspase-8 exon
      1, that acts as promoter in caspase-8-positive, but not in caspase-8-negative
      neuroblastoma (NB) cells. The P-1161/+16 DNA element regulates both constitutive
      and interferon IFN-gamma-inducible caspase-8 expression. Two GAS (IFN-activated
      sequence, STAT-1 binding site) and two ISRE (interferon sensitive response
      element, IRF binding site) were present in P-1161/+16. Deletion studies indicated
      that elements essential for promoter activity in NB cells were present in a 167
      bp region 5' flanking exon-1 (P-151/+16), which contains an ISRE at position -32.
      The transcription initiation site was mapped by 5' rapid amplification of cDNA
      end (RACE) at position -20 from caspase-8 cDNA reference sequence. Disruption of
      the ISRE-32 indicated that it is required for both constitutive and IFN-gamma
      inducible caspase-8 expression. IRF-1 and IRF-2 transcription factors bind to the
      (-151/+16) DNA fragment in vitro. Chromatin immunoprecipitation (ChIP) assays
      showed that IRF-1 and IRF-2 bind to the DNA region at the 5' of caspase-8 gene in
      NB cells, which show constitutive expression but not in caspase-8 negative cells.
      In these last cells, up-regulation of caspase-8 by IFN-gamma was associated to
      induction of IRF-1 and IRF-2 binding to caspase-8 promoter and increased histone
      acetylation. Moreover, RNA interference experiments also supported the
      involvement of IRF-1 and IRF-2 in constitutive caspase-8 expression in NB cells.

PMID- 17036320
TI  - Combined human papillomavirus DNA and human papillomavirus-like particle
      serologic assay to identify women at risk for high-grade cervical intraepithelial
      neoplasia.
AB  - The objective of this study was to assess the utility of a second generation
      human papillomavirus (HPV) virus-like particle (VLP)-based ELISA as an adjunct to
      HPV DNA testing to identify women at risk for high-grade cervical intraepithelial
      neoplasia (CIN). Participants provided blood, cervical samples and interviewer
      obtained questionnaire information. HPV VLPs for types 16, 18, 33, 45 and 52 were
      produced using a baculovirus expression system. These highly purified VLPs were
      used in a polymer-based ELISA test. Cases with biopsy-confirmed CIN (CIN I, n =
      237; CIN II, n = 56; CIN III, n = 48) and controls (n = 351) with normal Pap
      smears were tested for HPV DNA by PCR and serologic response to multiple
      oncogenic HPV VLPs. 258/341 (76%) of cases and 230/351 (65.5%) of control
      patients had any type of HPV VLP antibody (OR = 1.63, 95% CI 1.16-2.30). More
      cases were seropositive than controls for each individual HPV type (p < 0.001 for
      HPV types 16, 18, 33 and 45; p = 0.06 for HPV 52). Reactivity to an increasing
      number of different HPV type-specific VLPs are associated with high-grade CIN
      independent of HPV DNA status. HPV VLP assays may be useful as an adjunct to HPV
      DNA testing in a subset of patients that needs to be defined by further studies.

PMID- 17036322
TI  - Associations between ocular melanoma and other primary cancers: an international
      population-based study.
AB  - Ocular melanoma is a rare neoplasm with a poorly understood etiology, especially
      concerning its link with ultraviolet-light exposure. Studying the risk of second
      primary cancers may help to formulate causal hypotheses. We used data from 13
      cancer registries, including 10,396 first occurring ocular melanoma cases, and
      404 second occurring cases. To compare the second cancer incidence in ocular
      melanoma patients to that in noncancer population, we calculated standardized
      incidence ratios (SIRs) of 32 types of cancer. We also calculated SIRs of second
      ocular melanoma after other primaries. Ocular melanoma patients had significantly
      increased risk of cutaneous melanoma (SIR = 2.38, 95% CI 1.77-3.14), multiple
      myeloma (SIR = 2.00, 1.29-2.95), and of liver (SIR = 3.89, 2.66-5.49), kidney
      (SIR = 1.70, 1.22-2.31), pancreas (SIR = 1.58, 1.16-2.11), prostate (SIR = 1.31,
      1.11-1.54), and stomach (SIR = 1.33, 1.03-1.68) cancers. Risks of cutaneous
      melanoma were highly variable between registries and were mainly increased in
      females, in younger patients, in first years following diagnosis, and for
      patients diagnosed after 1980. The risk of ocular melanoma was significantly
      increased only after prostate cancer (SIR = 1.41, 1.08-1.82). Risk of cutaneous
      melanoma after ocular melanoma had epidemiological patterns, similar to cutaneous
      melanoma screening in the general population. The increased risk of cutaneous
      melanoma would be largely due to greater skin cancer surveillance in ocular
      melanoma patients, and not to common etiological factors. The high SIR found for
      liver cancer may be explained by misclassification bias. Common etiological
      factors may be involved in ocular and prostate cancers.

PMID- 17036323
TI  - Prospective study of body mass index, height, physical activity and incidence of
      bladder cancer in US men and women.
AB  - We evaluated prospectively the association between body mass index (BMI), height,
      recreational physical activity and the risk of bladder cancer among US adults.
      Data were used from 2 ongoing cohorts, the Health Professionals Follow-up Study
      and the Nurses' Health Study, with 3,542,012 years of follow-up and 866 incident
      bladder cancer cases (men = 507; women = 359) for the anthropometric analysis and
      1,890,476 years of follow-up and 706 incident bladder cancer cases (men = 502;
      women = 204) for the physical activity analysis. Cox proportional hazard models
      were used to estimate incidence rate ratios (RR) and 95% confidence intervals
      (CI) between BMI, height, physical activity and bladder cancer risk adjusting for
      age, pack-years of cigarette smoking and current smoking. Estimates from each
      cohort were pooled using a random-effects model. We observed no association
      between baseline BMI and bladder cancer risk, even when we compared a BMI of > or
      =30 kg/m(2) to a BMI of 18-22.9 kg/m(2) [pooled multivariate (MV) RR, 1.16; 95%
      CI: 0.89-1.52]. A weak, but statistically significant, association was observed
      for the same comparison after excluding bladder cancer cases diagnosed within the
      first 4 years of follow-up (pooled MV RR, 1.33; 95% CI: 1.01-1.76). Height was
      not related to bladder cancer risk (pooled MV RR, 0.82; 95% CI: 0.65-1.03, top
      vs. bottom quintile). Total recreational physical activity also was not
      associated with the risk of bladder cancer (pooled MV RR, 0.97; 95% CI: 0.77
      1.24, top vs. bottom quintile). Our findings do not support a role for BMI,
      height or physical activity in bladder carcinogenesis.

PMID- 17036324
TI  - Smoking and alcohol drinking in relation to risk of gastric cancer: a population
      based, prospective cohort study.
AB  - The relations between tobacco, alcohol and risk of gastric cancer need to be
      established, and any gain from preventive measures should be estimated. We
      conducted a population-based, prospective cohort study in Nord-Trondelag county
      in Norway. During 1984-1986, adult residents were invited to a health survey and
      they answered questionnaires that assessed exposure to tobacco and alcohol,
      together with potential confounding factors. The exposure assessment regarding
      alcohol was limited to a 14-day period. New gastric cancers that occurred during
      follow-up (1984-2002) were identified by linkage to the Norwegian Cancer
      Registry. Cox proportion hazards regression models were used to calculate hazard
      ratios (HRs) with 95% confidence intervals (CI), adjusted for sex, education and
      body mass index. Follow-up of 1,117,648 person-years at risk among 69,962 cohort
      members revealed 251 gastric cancers, including 224 noncardia cancers. The risk
      was almost twice as high in daily smokers (HR = 1.88 [CI 95% = 1.33-2.67]) as in
      never smokers. Independent dose-response relations were found with earlier age at
      initiation (p = 0.02), frequency (p = 0.00) and duration of smoking (p = 0.00).
      Attributable risk (AR) of gastric cancer among current smokers was 8.7/100,000
      person-years and the corresponding population AR was 18.4%. No statistically
      significant associations between various degrees of exposure to alcohol and risk
      of gastric cancer was revealed, but combined high use of cigarettes (>20/day) and
      alcohol (>5 occasions/14 days) increased the risk of noncardia gastric cancer
      nearly 5-fold (HR = 4.90 [95% CI = 1.90-12.62]), compared to nonusers. It is
      concluded that smoking is a dose-dependent risk factor for gastric cancer.
      Combined high exposure to smoking and alcohol further increases the risk.
      Successful preventive measures could considerably reduce the incidence of gastric
      cancer.

PMID- 17036325
TI  - The changing incidence and sites of colorectal cancer in the Israeli Arab
      population and their clinical implications.
AB  - Israeli Arabs have been at low risk for colorectal cancer (CRC) and had mainly
      proximal cancer, but increasing CRC is now noted. We examined this trend and CRC
      site and compared them to the total Jewish population and to the low-risk Jews of
      Asian-African origin. Israel Cancer Registry CRC data, 1982-2002, for Arabs and
      Jews was computed by gender, age and site: rectal cancer included recto-sigmoid
      junction; "right-sided" CRC included the proximal colon up to and also the
      splenic flexure. During 1982-2002, Arab CRC trends increased significantly in
      both sexes due to left-sided CRC (women, p = 0.01; men, p = 0.02) and rectal
      cancers (p = 0.05). Left-sided CRC increased significantly in both men and women
      aged > or = 65 years (p = 0.02). Comparing 1982-1984 to 2000-2002, the proportion
      of right-sided CRC decreased in both genders (p < 0.01) from 39.4 to 27.1% of
      male CRC, and from 44.8 to 31.3% in females. In general, this pattern of
      increasing rectal and left-sided CRC had been seen over a decade earlier in Jews
      of Asian-African origin and then their trend reversed during the last decade. In
      conclusion, there is a recent trend for left-sided CRC in Israeli Arabs, probably
      related to their changing life style. These results should influence their cancer
      preventive lifestyle recommendations, and CRC screening and diagnostic
      methodologies used.

PMID- 17036326
TI  - Bulky DNA adducts as risk indicators of lung cancer in a Danish case-cohort
      study.

PMID- 17036327
TI  - Exploring the joint effects of silicosis and smoking on lung cancer risks.
AB  - Cigarette smoking and silicosis are potential causes of lung cancer among workers
      exposed to silica dust, but their joint effects are unclear. We explored the
      possible interactions between silicosis and smoking on lung cancer risks by
      summarizing data from the published literature. The standardized mortality ratio
      or standardized incidence ratio reported in each published report was first
      adjusted using "smoking adjustment factors" to correct for the biased estimation
      of the expected numbers of lung cancer among smokers and nonsmokers when using
      general population rates in the indirect standardization process. The ratio of
      the effect of silicosis on lung cancer risk among smokers to that among nonsmoker
      was calculated and named the "relative silicosis effect (RSE)". The synergy index
      was estimated to assess the additive interaction. Metaanalyses were used to
      obtain the weighed means of the RSE and synergy index. Ten cohort studies were
      reviewed and combined to yield a weighed RSE of 0.29 (95% CI: 0.20, 0.42),
      indicating negative risk-ratio multiplication between smoking and silicosis on
      the lung cancer risk. The combined weighed synergy index was 1.00 (95% CI: 0.79,
      1.26), suggesting no departure from additivity. Sensitivity analyses showed that
      both estimates were quite robust. The independent risk-ratio effect of silicosis
      on lung cancer in smokers was about 30% of that in nonsmokers, and the joint
      effects of smoking and silicosis on the risk of lung cancer did not deviate from
      additivity and hence did not support biological synergism/antagonism.

PMID- 17036328
TI  - Re: "Bulky DNA adducts as risk indicators of lung cancer in a Danish case-cohort
      study".

PMID- 17036329
TI  - Rapid fat suppression in MRI of the breast with short binomial pulses.
AB  - PURPOSE: To develop a faster method of fat suppression for use in dynamic
      contrast enhanced MRI of the breast. MATERIALS AND METHODS: A method of fast fat
      suppression is presented using spatially nonselective rapid binomial pulses. In
      contrast to conventional binomial frequency-selective pulses, these short pulses
      are applied without interpulse delay, allowing for very rapid spectrally
      selective excitation. RESULTS: Effective water excitation and fat suppression
      were achieved in breast MRI at 3.0 Tesla with total excitation time as low as 160
      microsec, which is several times shorter than the excitation time of currently
      used fat suppression techniques. Rapid fat suppression comes at the expense of
      increased specific absorption rate (SAR) and mildly degraded quality of
      suppression. A flexible tradeoff of short imaging time vs. SAR can be made to
      optimize imaging speed for fat-suppressed breast MRI. CONCLUSION: Rapid binomial
      pulses can be used for dynamic contrast enhanced breast MRI with excitation times
      significantly shorter than currently used fat suppression pulses. Shorter
      excitation time allows more rapid imaging, allowing greater temporal and spatial
      resolution for characterization of breast lesions.

PMID- 17036330
TI  - Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and
      in vitro.
AB  - Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive
      apoptotic protein with the ability to specifically induce apoptosis in tumor
      cells. To explore the use of the Apoptin gene in cancer gene therapy, we
      constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV
      Apoptin) and compared the tumor-killing activity of the recombinant virus with
      that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found
      that although cells were somewhat resistant to the basal cytotoxic effect of wild
      type fowlpox virus, infection with vFV-Apoptin caused a pronounced, additional
      cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were
      apparent in the vFV-Apoptin-infected cells. We also tested whether fowlpox virus
      mediated expression of Apoptin in tumor cells could stimulate an antitumor effect
      by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells
      in C57BL/6 mice with vFV-Apoptin. We found that fowlpox virus-mediated
      intratumoral expression of the Apoptin gene can induce protective and therapeutic
      antitumor effects and significantly increase survival. Taken together, these data
      indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits
      tumor growth, induces apoptosis and may be an effective cancer treatment.

PMID- 17036331
TI  - Interactive effects of lifetime alcohol consumption and alcohol and aldehyde
      dehydrogenase polymorphisms on esophageal cancer risks.
AB  - In our previous study, we found that polymorphisms of alcohol and aldehyde
      dehydrogenase (ADH1B and ALDH2) are important risks for esophageal squamous cell
      carcinoma in a Taiwanese population. In this study, we increased the sample size
      to investigate the modifying effect of lifetime alcohol consumption on the
      association between ADH1B and ALDH2 genotypes and the risks of esophageal cancer.
      A multicenter hospital-based case-control study was conducted between August 2000
      and June 2004. Three hundred and thirty newly-diagnosed esophageal squamous cell
      carcinoma patients and 592 controls were recruited from National Taiwan
      University Hospital in Taipei and Kaohsiung Veterans General Hospital and
      Kaohsiung Medical University Hospital in Kaohsiung, Taiwan. Controls were matched
      to the case patients by gender and age within 4 years (case:control = 1:1-4).
      Polymorphisms of ADH1B and ALDH2 were genotyped by the method of PCR-RFLP.
      Individuals with ADH1B*1/*1 genotype had a 3.99-fold risk (95% CI = 2.13-7.48) of
      developing esophageal cancer, compared with those with ADH1B*2/*2 genotype, after
      adjusted for appropriate covariates. Individuals with ALDH2*1/*2 and ALDH2*2/*2
      had 4.99-fold risk (95% CI = 3.11-7.99) and 4.24-fold risk (95% CI = 1.52-11.84),
      respectively, of developing esophageal cancer, compared with those with
      ALDH2*1/*1, after adjusted for appropriate covariates. We also found a modifying
      effect of lifetime alcoholic consumption on the association between genotypes of
      ADH1B and ALDH2 on esophageal cancer risk. These results suggest that ADH1B and
      ALDH2 polymorphisms play a pivotal role on esophageal cancer and that the effect
      of these polymorphisms was modified by the amount of alcohol consumed.

PMID- 17036332
TI  - Unbalanced expression of licensing DNA replication factors occurs in a subset of
      mantle cell lymphomas with genomic instability.
AB  - DNA licensing is a crucial process for chromosome replication control.
      Deregulation of the licensing factors Cdt1, Cdc6 and the licensing inhibitor
      geminin has been associated with DNA replication defects and chromosomal
      instability. We examined the expression of these factors, in mantle cell lymphoma
      (MCL) and non-neoplastic lymphoid samples, and analysed the potential role of
      their deregulation in genomic instability. Geminin, Cdt1 and Cdc6 were
      coordinately expressed in non-neoplastic tissues and most MCL in relationship to
      the proliferative activity of the cells. However, 6 (18%) tumours showed an
      unbalanced "licensing signature" characterized by a higher expression of Cdt1 and
      Cdc6 than the negative regulator geminin. Tumours with this unbalanced signature
      and p53/p14(ARF) alterations had significantly higher number of chromosome
      abnormalities than lymphomas with p53/p14(ARF) alterations but with a normal
      licensing signature. No aberrations of Cdct1, Cdc6, and geminin genes were
      detected in cases with unbalanced licensing. However, tumours with p53/ARF
      inactivation and unbalanced licensing signature had significantly higher cyclin
      D1 levels than tumours with normal licensing signature. These results suggest
      that an unbalanced mRNA expression of licensing regulatory genes may play a role
      in the pathogenesis of the chromosomal instability of a subset of MCL with
      inactivation of the p53/p14(ARF) pathway.

PMID- 17036333
TI  - SPAN-XB core promoter sequence is regulated in myeloma cells by specific CpG
      dinucleotides associated with the MeCP2 protein.
AB  - SPAN-Xb is a novel cancer-testis antigen in multiple myeloma. We recently
      demonstrated that SPAN-Xb expression in myeloma cells is regulated through
      promoter methylation and could be upregulated by IL-7 and GM-CSF. In this present
      study, we set out to investigate the mechanism of SPAN-XB expression and the
      promoter association with the methyl-CpG binding protein (MeCP2). Elucidation of
      these interactions is likely shed light on potential therapeutic strategies to
      upregulate antigen levels for SPAN-Xb-based tumor vaccines. Using a panel of
      truncated promoter constructs, we localize the core sequence of SPAN-XB promoter
      to the 73 bp at the 3' end of the promoter, a region within the full length
      promoter that lacks CpG dinucleotides. Reporter gene expression assays showed
      that the core promoter function is significantly modulated by the adjacent CpG
      sequences. Chromatin immunoprecipitation assays revealed a specific association
      of MeCP2 with the promoter, and MeCP2 binding strongly correlated with repression
      of SPAN-XB gene. Reactivation of the SPAN-XB gene by 5-azacytidine treatment
      resulted in the loss of MeCP2 from this site. We, therefore, conclude that SPAN
      XB core promoter function in myeloma cells is associated with MeCP2 protein
      binding and regulated by specific CpG dinucleotide sequences.

PMID- 17036334
TI  - Trigonocephaly in Muenke syndrome.
AB  - Saethre-Chotzen syndrome is caused by mutations in the TWIST gene on chromosome
      7p21.2. However, Muenke et al. [(1997); Am J Hum Genet 91: 555-564] described a
      new subgroup carrying the Pro250Arg mutation in the fibroblast growth factor
      receptor (FGFR) 3 gene on chromosome 4p16. Uni or bicoronal synostosis appears to
      be the main clinical finding in both syndromes. We observed trigonocephaly as a
      new manifestation in Muenke syndrome. As a consequence we advise to routinely
      perform mutation analysis of the FGFR1, 2, and 3 genes in children with non
      syndromic trigonocephaly.

PMID- 17036335
TI  - CRELD1 mutations contribute to the occurrence of cardiac atrioventricular septal
      defects in Down syndrome.

PMID- 17036336
TI  - Whole genome microarray analysis of gene expression in an imprinting center
      deletion mouse model of Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes in
      the 15q11-q13 region. To further characterize alterations in gene expression in
      this classical obesity syndrome we used whole genome microarrays to study a PWS
      mouse model resulting from a paternally derived imprinting center (IC) deletion
      (PWS IC deletion). These mice die generally within 2-3 days of life (reflective
      of failure to thrive in infants with PWS) and therefore, the analysis was
      performed on RNA extracted from the whole brain of PWS IC deletion mice and
      normal littermates at less than 24 hr after birth. Of more than 45,000 probes
      examined, 26,471 (59%) were detected for further analysis, and 69 had a
      significant change in expression of at least 1.5-fold and a false discovery rate
      (FDR) of 5%. Eight of the genes with differential expression were imprinted and
      from the PWS critical region (PWSCR). The three genes with the highest expression
      in the PWS IC mice were pro-opiomelanocortin (Pomc) and two transcripts of
      unknown function. Pomc knockout mice have been shown to develop obesity.
      Therefore, elevated Pomc RNA in PWS IC deletion neonatal mice may be an important
      genetic factor in the survival of these mice as it may affect eating behavior.
      Interestingly, Mc5r, a melanocortin receptor known to directly respond to Pomc
      expression changes, was upregulated as well. Mc5r is known to be involved with
      thermoregulation which is reportedly abnormal in PWS infants. These observations
      support a role for Pomc and the network of genes involved in regulating energy
      homeostasis in the early clinical findings of failure to thrive observed in PWS.
      Other notable patterns include three previously unstudied transcripts that are
      expressed only from the paternal allele under regulatory control of the IC and
      include AK013560, BB3144814, and BB182944 (whose genes are located in the mouse
      PWSCR on chromosome 7B). As expected, all the known paternally expressed genes
      from the PWSCR had detection signals below the threshold in the PWS IC deletion
      mice but were clearly detectable in control littermates. Several of the genes in
      this study were further examined by quantitative reverse transcription-PCR (RT
      PCR) to confirm their expression status. Further analysis of gene expression in
      these mice may lead to novel pathways affected in PWS. These results, along with
      other recent reports, suggest that the cumulative effect of modest changes in
      expression of many genes, especially genes involved in energy metabolism,
      contribute to the failure to thrive of infants with PWS.

PMID- 17036337
TI  - Risks of human limb deficiency anomalies associated with 29 SNPs of genes
      involved in homocysteine metabolism, coagulation, cell-cell interactions,
      inflammatory response, and blood pressure regulation.
AB  - This study explored risks of limb deficiency anomalies associated with 29 single
      nucleotide polymorphisms (SNPs) of genes involved in homocysteine metabolism,
      coagulation, cell-cell interaction, inflammatory response, and blood pressure
      regulation. The authors genotyped 96 cases and 437 non-malformed controls from a
      California population-based case-control study (1987-1988 birth cohort).
      Increased risk of limb anomaly was observed for three SNPs: heterozygosity for F5
      Arg506Gln, with an odds ratio (OR) of 2.5 (95% confidence interval (CI), 1.0,
      6.5); heterozygosity for TNF (-376)G > A, OR 2.1 (0.7, 6.2); and homozygosity for
      NPPA 2238T > C, OR 4.0 (1.1, 15.4). We hypothesized that effects of variant
      genotypes in the presence of maternal smoking, and/or in the absence of
      supplement intake, may exceed effects of any of these factors alone. In
      particular, findings for polymorphisms in SERPINE1, ITGA2, SELE, TNF, LTA, NPPA,
      GNB3, and ADRB2 supported the hypotheses, both for smoking and for supplement
      intake. These results suggest involvement of genetic variation of biologically
      relevant candidate genes, and gene-environment interaction, for some limb
      anomalies whose pathogenesis may be related to altered vascular tone or
      integrity.

PMID- 17036338
TI  - X-chromosome inactivation patterns in females with Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by
      loss of paternally expressed genes from the 15q11-q13 region generally due to a
      paternally-derived deletion of the 15q11-q13 region or maternal disomy 15 (UPD).
      Maternal disomy 15 is usually caused by maternal meiosis I non-disjunction
      associated with advanced maternal age and after fertilization with a normal sperm
      leading to trisomy 15, a lethal condition unless trisomy rescue occurs with loss
      of the paternal chromosome 15. To further characterize the pathogenesis of
      maternal disomy 15 process in PWS, the status of X-chromosome inactivation was
      calculated to determine whether non-random skewing of X-inactivation is present
      indicating a small pool of early embryonic cells. We studied X-chromosome
      inactivation in 25 females with PWS-UPD, 35 with PWS-deletion, and 50 controls
      (with similar means, medians, and age ranges) using the polymorphic androgen
      receptor (AR) gene assay. A significant positive correlation (r = 0.5, P = 0.01)
      was seen between X-chromosome inactivation and age for only the UPD group.
      Furthermore, a significantly increased level (P = 0.02) of extreme X-inactivation
      skewness (>90%) was detected in our PWS-UPD group (24%) compared to controls
      (4%). This observation could indicate that trisomy 15 occurred at conceptus with
      trisomy rescue in early pregnancy leading to extreme skewness in several PWS-UPD
      subjects. Extreme X-inactivation skewness may also lead to additional risks for X
      linked recessive disorders in PWS females with UPD and extreme X-chromosome
      skewness.

PMID- 17036339
TI  - In vivo measurement of plaque burden in a mouse model of Alzheimer's disease.
AB  - PURPOSE: To demonstrate an MRI method for directly visualizing amyloid-beta
      (Abeta) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that
      T1rho relaxation rate increases progressively with Alzheimer's disease (AD)
      related pathology in the tg mouse brain. MATERIALS AND METHODS: We obtained in
      vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid
      precursor protein, and measured T1rho via quantitative relaxometric maps.
      RESULTS: A significant decrease in T1rho was observed in the cortex and
      hippocampus of 12- and 18-month-old animals compared to their age-matched
      controls. There was also a correlation between changes in T1rho and the age of
      the animals. CONCLUSION: T1rho relaxometry may be a sensitive method for
      noninvasively determining AD-related pathology in APP/PS1 mice.

PMID- 17036340
TI  - Role of MRI in screening women at high risk for breast cancer.
AB  - Breast cancer is diagnosed in over one million women worldwide every year. Until
      breast cancer can be prevented, early detection offers the best chance for cure.
      Mammographic screening is an effective method for early detection in average-risk
      women. However, the sensitivity of mammography is decreased in women at high risk
      for breast cancer. Because of its high sensitivity, multiple investigators have
      studied the potential role of MRI in screening women at high risk. In the past
      few years, results from eight major clinical trials exploring breast MRI as a
      screening tool have been published. Combined, the studies included 4271 patients
      and found 144 breast cancers detected by MRI, for an overall cancer yield of 3%.
      The sensitivity of MRI ranged from 71% to 100% across the studies. Although its
      reported specificity was variable, the call-back rates and risk of benign
      biopsies were within acceptable limits. In general, patients who underwent breast
      MRI screening had a 10% risk of being called back, and a 5% risk of having a
      benign biopsy. This work reviews the literature and current practices and
      recommendations for MRI as a screening tool for high-risk women.

PMID- 17036342
TI  - Myocardial perfusion.
AB  - Noninvasive cardiac magnetic resonance (CMR) imaging has progressed rapidly over
      the past few years and will most likely become an integral part of the diagnostic
      workup of patients with known or suspected coronary artery disease (CAD). In this
      article the rationale for using perfusion-CMR is discussed, followed by a summary
      of current state-of-the-art perfusion-CMR techniques that addresses
      pharmacological stress, monitoring, pulse sequences, and doses of contrast media
      (CM) for first-pass studies. In the second part, unresolved aspects of perfusion
      CMR, such as the lack of fully established and validated imaging protocols, are
      discussed. The optimum pulse sequence parameters, required cardiac coverage,
      analysis algorithms, criteria for data quality, and other aspects remain to be
      defined. Furthermore, since expertise in perfusion-CMR is not yet widely
      available, training of physicians and technicians to perform perfusion-CMR
      according to recognized standards is an important future requirement. In the last
      part of the review, some ideas are proposed to improve the management of patients
      with known or suspected CAD. This involves making a shift from a "reactive"
      strategy, in which patients are typically approached when they are symptomatic,
      to an "active" strategy, in which perfusion-CMR is performed for early detection
      of high-risk patients so that revascularizations can be performed before
      potentially deadly infarcts occur. An ideal test for such an active strategy
      would be highly accurate, reliable, safe (and thus repeatable), and affordable.
      Large multicenter trials have shown that in experienced centers perfusion-CMR is
      reliable and repeatable, and it is hoped that future studies will demonstrate its
      cost-effectiveness as well.

PMID- 17036341
TI  - Analysis of a Scottish founder effect narrows the TAPVR-1 gene interval to
      chromosome 4q12.

PMID- 17036343
TI  - Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common
      cortical malformation.
AB  - Several brain malformations have been described in rare patients with the
      deletion 22q11.2 syndrome (DEL22q11) including agenesis of the corpus callosum,
      pachygyria or polymicrogyria (PMG), cerebellar anomalies and meningomyelocele,
      with PMG reported most frequently. In view of our interest in the causes of PMG,
      we reviewed clinical data including brain-imaging studies on 21 patients with PMG
      associated with deletion 22q11.2 and another 11 from the literature. We found
      that the cortical malformation consists of perisylvian PMG of variable severity
      and frequent asymmetry with a striking predisposition for the right hemisphere (P
      = 0.008). This and other observations suggest that the PMG may be a sequela of
      abnormal embryonic vascular development rather than a primary brain malformation.
      We also noted mild cerebellar hypoplasia or mega-cisterna magna in 8 of 24
      patients. Although this was not the focus of the present study, mild cerebellar
      anomalies are probably the most common brain malformation associated with
      DEL22q11.

PMID- 17036344
TI  - A case surviving for over a year of renal tubular dysgenesis with compound
      heterozygous angiotensinogen gene mutations.
AB  - Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal
      proximal tubules found in patients with Potter syndrome. We report a female
      newborn with RTD who has survived for more than 18 months. Infusions of fresh
      frozen plasma (FFP) in the early neonatal period were effective in raising and
      maintaining her blood pressure. Peritoneal dialysis was required until the
      appearance of spontaneous urination at 29 days after birth. Histopathological
      examinations of the kidney revealed dilated renal tubular lumina and foamy
      columnar epithelial cells in the renal tubules. Endocrinological studies showed a
      discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active
      renin concentration (135,000 pg/ml), suggesting an aberration in the renin
      substrate, angiotensinogen. Direct sequencing analysis revealed two novel
      mutations in the coding region of the angiotensinogen gene (AGT): a nonsense
      mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in
      exon 5 (c.1290delT). The mutations were in the compound heterozygous state,
      because each parent had each mutation. These findings suggest that
      angiotensinogen deficiency is one of the causes of RTD. A treatment of the
      condition with FFP may help to promote long survival.

PMID- 17036345
TI  - Associated malformations in congenital diaphragmatic hernia cases in the last 15
      years in a tertiary referral institute.
AB  - This is a review of cases of perinatally diagnosed congenital diaphragmatic
      hernia (CDH) with associated malformations with regard to time of diagnosis, side
      of hernia, associated malformations, and outcome. The authors analyzed the data
      of CDH cases with associated malformations from records of the I. Department of
      Obstetrics and Gynecology, Semmelweis University Faculty of Medicine, Budapest,
      between July 1, 1990 and June 30, 2005. The observed period was analyzed in two
      parts. The pre- and postnatal examinations verified CDH in 100 cases, 71% of
      which were associated with other malformations. In 52% (37/71) CDH was diagnosed
      before the 24th week of gestation. The rate of early diagnosed cases doubled in
      the second period. Ten percent (7/71) of cases were verified postnatally. Between
      1990 and 1997, the percentage of right-sided hernia was 6% (2/34) while in the
      second period it was 19% (7/37). The association with cardiovascular, chest, and
      craniofacial anomalies doubled in the second period, while association of central
      nervous system anomalies halved. Chromosome anomalies were verified in four
      cases. Pregnancy was terminated in 53% (34/64) and 13% (4/30) of newborn infants
      survived the perinatal period. Intrauterine or intrapartum death occurred in 8%
      (5/64) of cases. The prevalence of cardiovascular, pulmonary, and craniofacial
      anomalies doubled, while that of central nervous system malformations decreased.
      The prevalence of other associated malformations has not changed significantly
      between the two periods. The improvement of technical facilities and accumulated
      experience make it possible to identify a higher number of associated
      malformations before the 24th week of gestation.

PMID- 17036346
TI  - Primary breast cancer phenotypes associated with propensity for central nervous
      system metastases.

PMID- 17036347
TI  - Visual function of police officers who have undergone refractive surgery.
AB  - INTRODUCTION: The visual acuity and contrast sensitivity of police recruits and
      officers was evaluated in both normal and dim illumination conditions to
      determine whether officers who have had refractive surgery have compromised night
      vision. METHODS: The control group consisted of 76 officers and recruits who have
      not had refractive surgery and the refractive surgery group consisted of 22
      officers and recruits who had refractive surgery. Visual acuity and contrast
      sensitivity were measured under both room illumination and dim illumination. The
      room illumination test series included high contrast acuity, low contrast acuity
      and Pelli-Robson contrast sensitivity. The dim illumination test series included
      high contrast acuity, low contrast acuity, Pelli-Robson contrast sensitivity,
      license plate number acuity (with and without glare) and the Mesotest. RESULTS:
      The general findings were that the refractive surgery group had lower acuity
      scores on low contrast targets in both room and dim light levels along with a
      reduction in the Mesotest scores with a glare source compared to the control
      group. CONCLUSIONS: Although refractive surgery police recruits and officers had
      reduced performance on some vision tests, these reductions were small and it is
      unlikely that their performance on vision related tasks would be compromised, on
      average. The major concern is the small number of refractive surgery candidates
      whose results were well outside the range of the non-surgical candidates. Their
      vision may be unacceptable for policing.

PMID- 17036348
TI  - Industrial Pseudomonas folliculitis.
AB  - INTRODUCTION: Complaints of poor water quality and skin rashes among workers at a
      US cardboard manufacturing facility were investigated to determine potential
      causes. METHODS: Employees were interviewed regarding work duties and health
      symptoms. Areas of dermatitis in affected employees were visually examined.
      Collected water samples were tested for potential chemical and microbial
      contaminants. RESULTS: A total of 27 employees were identified with complaints of
      recent skin rashes affecting primarily the upper and lower extremities.
      Dermatitis complaints were associated with water contact and work in areas with
      poor water quality. Water testing showed high levels of Pseudomonas aeruginosa.
      Other tested substances were not at levels of concern. CONCLUSIONS: Overgrowth of
      P. aeruginosa occurred in the water system shortly after the facility switched to
      a closed-loop water recycling system and was the most likely cause of the
      observed dermatitis. To our knowledge, this is the first reported outbreak of
      Pseudomonas folliculitis in an industrial setting.

PMID- 17036349
TI  - North American Guidelines for Children's Agricultural Tasks: five-year assessment
      and priorities for the future.
AB  - BACKGROUND: The North American Guidelines for Children's Agricultural Tasks
      (NAGCAT) are a safety resource created to assist parents in selecting safe work
      for their children 7-16 years of age. Since their release in 1999, a growing body
      of scientific evidence has accumulated regarding NAGCAT. The purpose of this
      project was to assess the current scientific and programmatic evidence regarding
      the efficacy and utilization of the NAGCAT resource in order to determine the
      priorities for the next 5 years. METHODS: A systematic, evidenced-based method
      was employed to accomplish the project objectives. Our data sources included
      results from a survey of agricultural safety practitioners and researchers, a
      comprehensive synthesis of the peer-reviewed literature, and recommendations from
      a priority-setting meeting. RESULTS: Five main priorities were identified: to
      address the perceptions and barriers associated with the use and non-use of the
      NAGCAT resource; to revise and re-format a core set of the guidelines; to develop
      a NAGCAT resource dissemination/marketing plan; to provide training and support
      for agricultural safety professionals and parents using NAGCAT; and to conduct
      further research to facilitate accomplishing these priorities. CONCLUSIONS: This
      assessment and priority identification process was successful in outlining the
      next steps for the NAGCAT resource. As we move toward 2010, those involved in
      pediatric agricultural injury prevention will have a blueprint to ensure that
      NAGCAT are an effective and widely used resource for preventing work-related
      injuries.

PMID- 17036350
TI  - Long hours of work in the U.S.: associations with demographic and organizational
      characteristics, psychosocial working conditions, and health.
AB  - BACKGROUND: There are relatively few studies of large national databases that
      contain information on working hours and health. The current study involved an
      analysis of data from a quality of work life (QWL) module developed for the 2002
      General Social Survey. This module collected work and health data from a
      representative sample of the U.S. population (N=1,744). METHODS: Descriptive
      analyses were conducted for five groups based on total hours worked per week:
      part-time (1-34 hr/week), full-time (35-40 hr/week), lower overtime (41-48
      hr/week), medium overtime (49-69 hr/week), and higher overtime (70+ hr/week).
      Multiple logistic regression examined the association between these five
      categories and several measures of health and well-being. RESULTS: Compared to
      full-time workers, the three groups of overtime workers were more likely to be
      male, white, and middle-aged, with higher levels of education and income. They
      were also more likely to be self-employed, salaried, work as independent
      contractors, have more than one job, and work split/irregular/on-call shifts.
      Although overtime work was characterized by higher levels of job stress and
      perceptions of overwork, it was also associated with increased levels of
      participation in decision making and opportunities to develop special abilities.
      Several significant associations emerged between hours of work and measures of
      health and well-being, particularly for respondents in the higher overtime group
      (70+ hr/week). CONCLUSION: Overtime workers differ from their part-time and full
      time counterparts in several important areas. Some of these differences tended to
      increase with the number of overtime hours worked, suggesting a linear
      relationship. However, caution is warranted before generalizing the results of
      this study to specific occupations or workplaces.

PMID- 17036351
TI  - Workers' compensation experience of Colorado agriculture workers, 2000-2004.
AB  - BACKGROUND: Agriculture is among the most hazardous of occupations. The lack of
      information regarding agriculture injuries or fatalities has been recognized as
      an obstacle for effective injury prevention. Workers' compensation claims data
      for non-fatal injuries among agriculture and agri-business workers in the State
      of Colorado between the years of 2000 and 2004. METHODS: Workers' compensation
      claims are utilized to estimate injury claim incidence rates, determine the
      distributions of sources, causes, types and body locations of injuries, and
      estimate the costs of these injuries. RESULTS: Colorado agriculture and agri
      business workers (e.g., cattle dealers, cattle or livestock raisers, dairy
      farmers) have high rates of injury claims, especially in sectors that involve
      interaction with animals or livestock. Grain milling operations had a high rate
      of injury claims among agri-business operations. Injuries related to animals,
      strains, machinery, and falls or slips were the most frequent among all
      occupations analyzed. CONCLUSIONS: Understanding the occurrence of injuries among
      Colorado agriculture and agri-business workers is critical to implementing and
      evaluating effective intervention programs for specific agriculture-related
      occupations. The development of safety interventions that address the worker
      animal interface, fall protection systems, machinery usage, and overexertion
      prevention strategies is recommended.

PMID- 17036352
TI  - Psychopathology in the Lujan-Fryns syndrome: report of two patients and review.
AB  - We report on two new patients, the propositus and his maternal uncle, with Lujan
      Fryns syndrome (LFS). One presented with mild mental retardation and both patient
      had Marfanoid habitus and similar craniofacial anomalies (they had a long and
      narrow face, small mandible, high-arched palate, and hypernasal voice) as
      previously reported by Lujan et al. in 1984 and Fryns and Buttiens in 1987. One
      of our patients had agenesis of the corpus callosum as described by Lujan. The
      second patient had an ascending aortic aneurysm like the patient described by
      Wittine et al. 1999. Both patients showed similar behavior and psychiatric
      disorders. In addition, we reviewed the literature for the presence of
      psychopathology in LFS. After studying the 32 published cases and the 2 described
      in this article, we found that more than 90% of the patients present with some
      type of psychopathology, the most frequent being an autistic-like disorder. In
      our opinion, the agenesis of the corpus callosum (complete or partial) and
      ascending aorta aneurysm are manifestations of LFS, and thus brain MRI and
      echocardiogram should be part of the routine evaluation. Additionally, the high
      prevalence of psychopathological alterations in these patients suggests the need
      for psychiatric evaluation at the time of diagnosis.

PMID- 17036354
TI  - Complications of combined modality treatment of primary lower extremity soft
      tissue sarcomas.
AB  - BACKGROUND: Correlations between various patient, tumor, and treatment
      characteristics and complications in patients undergoing combined modality
      treatment for primary lower extremity soft-tissue sarcomas were investigated.
      METHODS: Using the M. D. Anderson Radiation Oncology database, the records of the
      subset of patients treated with combined radiation and limb-sparing surgery for
      primary lower extremity soft-tissue sarcomas were retrospectively reviewed from
      the years 1960 to 2003. RESULTS: In all, 412 patients were identified. With a
      median follow-up of 9.3 years, there were a total of 113 (27%) acute wound
      complications and 41 (13% at 20 years) chronic radiation-related limb
      complications. Preoperative radiation and tumor sizes >5 cm were associated with
      an increased risk of acute wound complications (34% preoperative vs. 16%
      postoperative, P < .001; and 31% >5 cm vs. 17% < or =5 cm, P = .005). At 20 years
      the radiation-related complication rate was higher in patients with a groin or
      thigh tumor location (16% vs. 4% other; P = .008), prior acute wound
      complications (20% vs. 10% no surgical complication), and a radiation dose > or
      =60 grays (Gy) (18% vs. 9% for dose < 60 Gy; P = .04). Five fractures occurred,
      resulting in a crude overall fracture rate of 1.2%. CONCLUSIONS: Patients treated
      with preoperative radiation for larger tumors are more likely to have acute
      surgical wound complications. Acute wound complications followed by postoperative
      radiation are associated with chronic radiation-related limb problems, as are
      higher radiation dose and proximal tumor location. The fracture rate is so low
      that prophylactic fixation is not warranted.

PMID- 17036355
TI  - Phase I clinical trial of bortezomib in combination with gemcitabine in patients
      with advanced solid tumors.
AB  - BACKGROUND: Bortezomib is the first proteasome inhibitor to show preliminary
      evidence of activity against solid tumors. Findings from preclinical studies
      prompted a Phase I trial to determine the maximum tolerated dose (MTD) and dose
      limiting toxicities (DLTs) of bortezomib in combination with gemcitabine in
      patients with recurring/refractory advanced solid tumors. The effect of
      gemcitabine on proteasome inhibition by bortezomib in whole blood was also
      investigated. METHODS: Bortezomib was administered as an intravenous bolus
      injection on Days 1, 4, 8, and 11, with gemcitabine (30-minute infusion) on Days
      1 and 8 of a 21-day cycle. Groups of > or =3 patients were evaluated at each dose
      level. Escalating doses of gemcitabine 500 mg/m(2) to 1000 mg/m(2) with
      bortezomib 1.0 mg/m(2) to 1.5 mg/m(2) were planned. RESULTS: There were no DLTs
      in patients receiving bortezomib 1.0 mg/m(2) and gemcitabine 500 mg/m(2) to 1000
      mg/m(2) in the first 3 dose levels. Dose-limiting nausea, vomiting,
      gastrointestinal obstruction, and thrombocytopenia occurred in 4 of 5 evaluable
      patients in dose level 4 (bortezomib 1.3 mg/m(2), gemcitabine 800 mg/m(2)),
      establishing bortezomib 1.0 mg/m(2) and gemcitabine 1000 mg/m(2) as the MTD. Most
      common Grade > or =3 toxicities were neutropenia (6 patients), thrombocytopenia
      (5 patients), gastrointestinal disorders (6 patients), and general disorders (4
      patients) such as fatigue. One patient with nonsmall cell lung carcinoma achieved
      a partial response and 7 achieved stable disease. Inhibition of 20S proteasome
      activity by bortezomib was unaffected by gemcitabine coadministration.
      CONCLUSION: Dosages of bortezomib and gemcitabine suitable for further evaluation
      of antitumor activity have been established.

PMID- 17036356
TI  - Abstracts of the American Society of Cytopathology 54th Annual Scientific
      Meeting, November 3-8, 2006, Toronto, Canada.

PMID- 17036357
TI  - Long-term safety of cardiac magnetic resonance imaging performed in the first few
      days after bare-metal stent implantation.
AB  - PURPOSE: To investigate the long-term safety of cardiac magnetic resonance
      imaging (CMR) performed one to seven days after coronary artery stent (bare
      metal) implantation. MATERIALS AND METHODS: We analyzed 119 consecutive patients
      with acute myocardial infarction (MI) who underwent emergency coronary stent
      implantation with a bare-metal stent. CMR using a 1.5T scanner was performed on
      51 patients (42.9%) at a mean of 2.7+/-3.1 days after stent implantation (CMR+
      group), and the remaining 68 patients (57.1%) served as controls (CMR- group).
      The patients were followed up to six months for major adverse cardiac events.
      RESULTS: The average stent size was 3.3+/-0.5x18.4+/-6.7 mm, and 86% of the
      stents were made of 316L stainless steel. There were no significant differences
      between the CMR+ and CMR- groups in terms of infarct features, angiographic
      findings, or stent characteristics. Over a mean follow-up of 4.4+/-2.1 months, 12
      patients (10.1%) had 16 events (13.4%). Two patients had adverse events after
      early MRI scan (4.3%), a rate that is lower than the event rate in the patients
      who did not undergo MRI (16%, P=0.04), and one of the two events was clearly not
      MRI related. CONCLUSION: CMR on a 1.5T scanner can be safely performed within one
      to seven days after coronary bare-metal stent implantation and is not associated
      with an increased risk of adverse clinical cardiac outcomes. In the light of
      accumulating data, the guidelines by stent manufacturers should be revised.

PMID- 17036358
TI  - Fluid-attenuated inversion-recovery SSFP imaging.
AB  - PURPOSE: To describe and evaluate a fast, fluid-suppressed 2D multislice steady
      state free precession (SSFP) neuroimaging sequence. MATERIALS AND METHODS: We
      developed a fast fluid-attenuated inversion-recovery SSFP sequence for use in
      neuroimaging. The inversion time (TI) was optimized to yield good cerebrospinal
      fluid (CSF) suppression while conserving white matter (WM)/lesion contrast across
      a broad range of flip angles. Multiple SSFP acquisitions were combined using the
      sum-of-squares (SOS) method to maximize SNR efficiency while minimizing SSFP
      banding artifacts. We compared our fluid-attenuated inversion-recovery (FLAIR)
      SSFP sequence with FLAIR fast spin-echo (FSE) in both normal subjects and a
      volunteer with multiple sclerosis. SNR measurements were performed to ascertain
      the SNR efficiency of each sequence. RESULTS: Our FLAIR SSFP sequence
      demonstrated excellent CSF suppression and good gray matter (GM)/WM contrast.
      Coverage of the entire brain (5-mm slices, 24-cm FOV, 256 x 192 matrix) was
      achieved with FLAIR SSFP in less than half the scan time of a corresponding FLAIR
      FSE sequence with similar SNR, yielding improvements of more than 50% in SNR
      efficiency. Axial scans of a volunteer with multiple sclerosis show clearly
      visible plaques and very good visualization of brain parenchyma. CONCLUSION: We
      have demonstrated the feasibility of a very fast fluid-suppressed neuroimaging
      technique using SSFP.

PMID- 17036359
TI  - EEG-fMRI using z-shimming in patients with temporal lobe epilepsy.
AB  - PURPOSE: To use z-shimming, a technique that reduces signal loss due to
      susceptibility artifacts that can result in reduced or absent activation in
      electroencephalography (EEG) functional MRI (fMRI) sessions in patients with
      temporal lobe epilepsy (TLE), to determine whether it would result in an
      increased ability to detect significant regions of blood oxygenation level
      dependent (BOLD) signal change. MATERIALS AND METHODS: Eight patients with TL EEG
      spikes underwent an EEG-fMRI scanning session using z-shimming. The signal
      intensities in the z-shimmed images were compared with those in the standard
      images. BOLD activation maps were created from the two sets of images using the
      timings of the spikes observed on the EEG. RESULTS: The mean signal increase in
      the TLs as a result of z-shimming was 45.9%+/-4.5%. The percentage of TL voxels
      above a brain intensity threshold rose from 66.1%+/-7.6% to 77.6%+/-5.7%. This
      appreciable increase in signal did not lead to any significant differences in the
      statistical maps created with the two sets of functional images. CONCLUSION: The
      results suggest that loss of signal is not the limiting factor for the detection
      of spike-related BOLD signal changes in patients with TLE activity.

PMID- 17036360
TI  - An unusual cause of susceptibility artifact in magnetic resonance imaging.
AB  - Magnetic susceptibility artifact has been documented with various implants and
      devices, which require appropriate identification with screening of patients
      prior to subjecting them to magnetic resonance examination. We performed
      cardiovascular magnetic resonance (CMR) examination of the aorta in a 24-year-old
      woman in the setting of repaired aortic coarctation, and found magnetic
      susceptibility artifact arising from the stomach in the absence of known
      susceptibility artifact-producing material in this region. Further history
      revealed that she had ingested a prenatal vitamin prior to imaging, prompting
      experimental analyses that led us to conclude that iron-containing vitamins may
      be a source of magnetic susceptibility artifact.

PMID- 17036361
TI  - Prognostic significance of [(18)F]fluorodeoxyglucose uptake on positron emission
      tomography in patients with pathologic stage I lung adenocarcinoma.
AB  - BACKGROUND: [(18)F]Fluoro-2-deoxyglucose uptake on positron emission tomography
      (FDG-PET) has been frequently used for diagnosis and staging of lung cancer. The
      prognostic significance of FDG uptake on PET was evaluated in patients with
      pathologic Stage I lung adenocarcinoma (tumor stages were based on the TNM
      classification of the International Union Against Cancer). METHODS: Disease-free
      survival of 98 patients with pathologic Stage I lung adenocarcinoma who were
      treated by curative resection was examined in relation to sex, age, histologic
      grade of differentiation, surgical procedure, tumor stage, and FDG uptake
      measured as the maximum standardized uptake value (SUV). RESULTS: Sixty-three
      patients were had Stage IA disease and 35 patients had Stage IB disease. Six
      patients each with Stage IA and Stage IB disease developed disease recurrence
      after a mean postsurgical follow-up period of 31 months. Ten (23%) of the 43
      patients with SUV > or = 3.3 developed a recurrence compared with 2 (4%) of the
      55 patients with SUV < 3.3 (P = .020). Ten (20%) of the 51 patients with
      moderately or poorly differentiated adenocarcinoma developed disease recurrence,
      compared with 2 (4%) of the 47 patients with well-differentiated adenocarcinoma
      (P = .056). Multivariate analysis demonstrated that histologic grade of
      differentiation was not correlated with the frequency of tumor recurrence (P =
      .286), whereas SUV was found to be marginally correlated (P = .079). CONCLUSIONS:
      FDG uptake appears to be predictive of disease-free survival in patients with
      Stage I lung adenocarcinoma. FDG uptake could yield important information for
      determining the likely value of postoperative adjuvant chemotherapy in such
      patients.

PMID- 17036363
TI  - Immunotoxic effects of chemicals: A matrix for occupational and environmental
      epidemiological studies.
AB  - BACKGROUND: Many biological and chemical agents have the capacity to alter the
      way the immune system functions in human and animals. This study evaluates the
      immunotoxicity of 20 substances used widely in work environments. METHODS: A
      systematic literature search on the immunotoxicity of 20 chemicals was performed.
      The first step was to review literature on immunotoxicity testing and testing
      schemes adopted for establishing immunotoxicity in humans. The second step
      consisted of providing a documentation on immunotoxicity of substances that are
      widely used in work environment, by building tables for each chemical of interest
      (benzene, trichloroethylene, PAHs, crystalline silica, diesel exhausts, welding
      fumes, asbestos, styrene, formaldehyde, toluene, vinyl chloride monomer,
      tetrachloroethylene, chlorophenols, 1,3-butadiene, mineral oils, P
      dichlorobenzene, dichloromethane, xylene, 1,1,1-trichloroethane, ethylene oxide).
      The third step was the classification of substances; an index (strong,
      intermediate, weak, nil) was assigned on the basis of the evidence of toxicity
      and type of immunotoxic effects (immunosuppression, autoimmunity,
      hypersensitivity) on the basis of the immune responses. Finally substances were
      assigned a score of immunotoxic power. RESULTS: Tables have been produced that
      include information for the 20 substances of interest, based on 227 animal
      studies and 94 human studies. Each substance was assigned an index of immunotoxic
      evidence, a score of immunotoxic power and type of immunotoxic effect.
      CONCLUSIONS: This matrix can represent a tool to identify chemicals with similar
      properties concerning the toxicity for the immune system, and to interpret
      epidemiological studies on immune-related diseases.

PMID- 17036362
TI  - Biomarkers of depression in cancer patients.
AB  - BACKGROUND: Inflammation and perturbation of the hypothalamic-pituitary-adrenal
      (HPA) axis function appears to play a putative role in the etiology of
      depression. Patients with metastatic cancer demonstrate elevated prevalence rates
      for depression. The objective of the current study was to illustrate the efficacy
      of interleukin-6 (IL-6) and HPA axis function as adjuncts to support the
      diagnosis of depression in cancer patients. METHODS: Plasma concentrations of IL
      6 and cortisol were measured in 114 cancer patients with and without depression.
      The relative diurnal variation of cortisol (cortisol VAR), expressed as a
      percentage, was calculated. Receiver operating characteristics analysis was
      performed. RESULTS: Depression was associated with increased plasma
      concentrations of IL-6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol
      concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%,
      respectively; P < .001) was found to be decreased in cancer patients with
      depression, indicating a disturbed circadian function of the HPA axis. As a
      biomarker of depression, IL-6 yielded at a cutoff value of 10.6 pg/mL, a
      sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86;
      95% confidence interval [95% CI], 0.78-0.94), whereas cortisol VAR demonstrated a
      sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74-0.97) at a
      cutoff value of 33.5%. CONCLUSIONS: Depression is associated with increased
      plasma IL-6 concentrations in patients with cancer. These patients demonstrate a
      dysfunction of the HPA-axis, characterized by a decreased diurnal variation of
      cortisol. The high sensitivity and specificity of these parameters biomarkers of
      depression make IL-6 and cortisol VAR helpful tools in the diagnosis of
      depression in patients with cancer.

PMID- 17036364
TI  - The Declaration of Brescia on prevention of the neurotoxicity of metals June 18,
      2006.

PMID- 17036365
TI  - Fungal biofiltration of alpha-pinene: effects of temperature, relative humidity,
      and transient loads.
AB  - Over the past decade much effort has been made to develop new carrier materials,
      more performant biocatalysts, and new types of bioreactors for waste gas
      treatment. In biofilters fungal biocatalysts are more resistant to acid and dry
      conditions and take up hydrophobic compounds from the gas phase more easily than
      wet bacterial biofilms. In the present study, a biofilter packed with a mixture
      of perlite and Pall rings and fed alpha-pinene-polluted air was inoculated with a
      new fungal isolate identified as Ophiostoma species. alpha-Pinene is a volatile
      pollutant typically found in waste gases from wood-related industries. The
      temperature of waste gas streams from pulp and paper industries containing alpha
      pinene is usually higher than ambient temperature. Studies were undertaken here
      on the effect on performance of temperature changes in the range of 15-40 degrees
      C. The effect of temperature on biodegradation kinetics in continuous reactors
      was elucidated through equations derived from the Arrhenius formula. Moreover,
      the effects of the relative humidity (RH) of the inlet gas phase, transient loads
      (shock or starvation), and the nature of the nitrogen source on alpha-pinene
      removal were also studied in this research. The results suggest that the fungal
      biofilter appears to be an effective treatment process for the removal of alpha
      pinene. The optimal conditions are: temperature around 30 degrees C, RH of the
      inlet waste gas stream around 85%, and nitrate as nitrogen source. The fungal
      biofilter also showed a good potential to withstand shock loads and recovered
      rapidly its full performance after a 3-7 days starvation period.

PMID- 17036366
TI  - All-cause mortality associated with atypical and typical antipsychotics in
      demented outpatients.
AB  - PURPOSE: To estimate the association between use of typical and atypical
      antipsychotics and all-cause mortality in a population of demented outpatients.
      METHODS: The study cohort comprised all demented patients older than 65 years and
      registered in the Integrated Primary Care Information (IPCI) database, during
      1996-2004. First, mortality rates were calculated during use of atypical and
      typical antipsychotics. Second, we assessed the association between use of
      atypical and typical antipsychotics and all-cause mortality through a nested case
      control study in the cohort of demented patients. Each case was matched to all
      eligible controls at the date of death by age and duration of dementia. Odds
      ratios were estimated through conditional logistic regression analyses. RESULTS:
      The crude mortality rate was 30.1 (95%CI: 18.2-47.1) and 25.2 (21.0-29.8) per 100
      person-years (PY) during use of atypical and typical antipsychotics,
      respectively. No significant difference in risk of death was observed between
      current users of atypical and typical antipsychotics (OR = 1.3; 95%CI: 0.7-2.4).
      Both types of antipsychotics were associated with a significantly increased risk
      of death as compared to non-users (OR = 2.2, 1.2-3.9 for atypical antipsychotics;
      OR=1.7, 1.3-2.2 for typical antipsychotics). CONCLUSIONS: Conventional
      antipsychotic drug should be included in the FDA's Public Health advisory, which
      currently warns only of the increased risk of death with the use of atypical
      antipsychotics in elderly demented persons.

PMID- 17036367
TI  - Synthesis and anti-tumor activities of novel pyrazolo[1,5-a]pyrimidines.
AB  - A series of novel pyrazolo[1,5-a]pyrimidines were designed and synthesized in
      order to find novel potent anti-tumor compounds. The structures of all the
      compounds were confirmed by IR, (1)H-NMR, elemental analysis, and MS. Their anti
      tumor activities against cancer cell lines were tested by the MTT method in
      vitro. Compound 19 displayed potent anti-tumor activity.

PMID- 17036368
TI  - Synthesis and antibacterial activity of nitroaryl thiadiazole-levofloxacin
      hybrids.
AB  - Novel levofloxacin-containing hybrids carrying a 5-(nitroaryl)-1,3,4-thiadiazol-2
      yl group were synthesized and evaluated in vitro against Gram-positive and Gram
      negative bacteria. Preliminary data indicated that levofloxacin-nitrofuran and
      levofloxacin-nitroimidazole hybrids have a potent activity against Gram-positive
      organisms with enhanced anti-staphylococcal activity compared with the parent
      quinolone (N-desmethyl levofloxacin).

PMID- 17036369
TI  - Novel synthesis of 1,3,4-thiadiazine derivatives and their cycloaddition
      reactions.
AB  - 4-Phenyl-3-thiosemicarbazide 1 reacted with the alpha-halocarbonyl compounds 2a,
      b to give the thiosemicarbazone derivatives 3a, b. The latter compounds underwent
      cyclization to the 1,3,4-thiadiazine derivatives 4a, b which underwent [2 + 4]
      cycloaddition reactions to give the 4H-thiopyran derivatives 7a, b. The chemistry
      of these thiopyrans was studied. Some of the fused derivatives among them
      compounds 20a, 20b, 21a, 21b allowed good mycelial growth and sporulation by the
      two fungi. This indicates that the two fungi can use the N-containing
      heterocyclic ring as a nitrogen source.

PMID- 17036370
TI  - The tubulin-bound conformation of discodermolide derived by NMR studies in
      solution supports a common pharmacophore model for epothilone and discodermolide.

PMID- 17036371
TI  - Catalytic, asymmetric synthesis of 1,4-benzoxazinones: a remarkably
      enantioselective route to alpha-amino acid derivatives from o-benzoquinone
      imides.

PMID- 17036372
TI  - Complete assignments 1H and 13C NMR spectral data of four anabaseine derivatives.
AB  - The anabaseine derivatives 6-methoxy-7-hydroxy-1-(pyridin-3-yl)-3,4
      dihydroisoquinoline, 6,7-dimethoxy-1-(pyridin-3-yl)-1,2,3,4
      tetrahydroisoquinoline and 6,7-dimethoxy-1-(piperidin-3-yl)-1,2,3,4
      tetrahydroisoquino- line were prepared either by demethylation with HBr or by
      reduction with different reagents, NaBH4 and H2/PtO2 from 6,7-dimethoxy-1
      (pyridin-3-yl)-3,4-dihydroisoquinoline, as starting material. The structures have
      been fully assigned by the combination of one- and two-dimensional experiments.

PMID- 17036373
TI  - Changes in medication associated with epilepsy-related hospitalisation: a case
      crossover study.
AB  - AIM: To assess the association between changes in medication and epilepsy-related
      hospitalisation. METHODS: Data were obtained from the PHARMO Record Linkage
      System (Jan 1998 to Dec 2002). We conducted a case-crossover study among patients
      with a first epilepsy-related hospital admission who had continuously used at
      least one antiepileptic drug (AED) during a 28-week period before admission. For
      each patient, changes in medication in a 28-day window before hospitalisation
      were compared with changes in four earlier 28-day windows. Evaluated changes
      were: changes in AEDs (pattern and dosage), changes in interacting co-medication
      and changes in non-interacting co-medication (i.e. introduction of non
      interacting drugs). The strength of the association between changes in medication
      and epilepsy-related hospitalisation was estimated using conditional logistic
      regression analysis and expressed as odds ratios (ORs) with 95% confidence
      intervals (CI). RESULTS: Out of 1185 patients with a first epilepsy-related
      hospitalisation, 217 patients met the inclusion criteria. Of the changes in
      antiepileptic therapy, discontinuation showed a trend towards an increased risk
      of hospitalisation (OR: 2.57; 95%CI: 0.81-8.17). Drug interactions influencing
      antiepileptic therapy rarely occurred. Introduction of three or more non
      interacting drugs was significantly associated with epilepsy-related
      hospitalisation (OR: 4.80; 95%CI: 2.12-10.87). Of individual drugs, addition of
      antimicrobial agents was significantly associated with epilepsy-related
      hospitalisation (OR: 1.99; 95%CI: 1.06-3.75). CONCLUSIONS: Changes in AED therapy
      were not significantly associated with epilepsy-related hospitalisation and few
      drug interactions influencing antiepileptic therapy occurred. However, patients
      starting three or more new non-AEDs had a nearly five times increased risk of
      epilepsy-related hospital admission.

PMID- 17036374
TI  - Myeloablative chemotherapy followed by autologous stem cell infusion may overcome
      the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations
      in patients with acute myeloid leukaemia and normal karyotype.
AB  - In this study, we analysed the prognostic relevance of foetal liver tyrosine
      kinase 3 (FLT3) mutations in 73 patients with acute myeloid leukaemia (AML) with
      normal karyotype, who survived induction and consolidation and received
      autologous stem cell transplantation (ASCT) after successful mobilization of
      peripheral blood stem cell (PBSC). There were 44 males and 29 females with a
      median age of 54 years (range 20-77). Overall, 16 out of 73 autografted patients
      (22%) had FLT3 mutations. More in detail, FLT3/ITDs were detected in 10 out of 73
      patients (14%), while FLT3 D835 mutations were detected in five cases (7%). One
      patient (1%) was found as having both abnormalities. White blood cell count
      (p=0.009), serum concentration of lactate dehydrogenase (p=0.01), and percentages
      of peripheral blood (p=0.002) and bone marrow blasts (p=0.03) were significantly
      higher in patients showing the FLT3 mutations. On the contrary, overall survival
      and disease-free survival were similar between patients with or without FLT3
      mutations (p=0.73 and 0.78, respectively). In conclusion, our data suggest that
      myeloablative chemotherapy supported by auto-PBSCT may overcome the adverse
      prognostic implications of FLT3 mutations in AML. However, it is to consider that
      autografted patients are highly selected for best response to induction,
      consolidation and mobilization, as well as for minor non-haematologic toxicity.

PMID- 17036375
TI  - Relevance of Ras gene mutations in the context of the molecular heterogeneity of
      multiple myeloma.
AB  - Ras gene mutations are a recurrent genetic lesion in multiple myeloma (MM). Here,
      we report a mutation analysis of N- and K-Ras genes in purified plasma cell
      populations from a panel of 81 newly diagnosed MM patients stratified according
      to the most frequent genetic and molecular features associated with the
      neoplasia. Ras gene mutations, mostly involving the N-Ras gene, were detected in
      20% of the patients. Ras mutations did not correlate with the presence of
      chromosome 13q deletion, trisomy of chromosome 11, 1q amplification or
      hyperdiploidy. In addition, despite an appreciable association with tumours
      overexpressing Cyclin D1, Ras mutations did not correlate at significant levels
      with any of the proposed groups in the TC classification, based on the presence
      of the major IgH chromosomal translocations and expression of Cyclin D genes.
      Finally, transcription analyses revealed the presence of differentially expressed
      transcripts in human multiple myeloma cell lines carrying the Ras gene mutations
      but not in primary tumours. Overall, these data suggest that Ras gene mutations
      are not likely to represent a master lesion in MM but its relevance needs to be
      considered in the context of other genetic abnormalities.

PMID- 17036376
TI  - Fertility among female hodgkin lymphoma survivors attempting pregnancy following
      ABVD chemotherapy.
AB  - Although ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy is
      infrequently associated with premature amenorrhea, little is known about the
      success rate of women attempting pregnancy following ABVD. In the present study
      females treated for HL with ABVD chemotherapy without pelvic radiation therapy
      (RT) and who were alive without relapse > or =3 years after treatment were
      identified from a clinical database and screened for inclusion. Using a
      standardized questionnaire, we determined the pregnancy rate (i.e. time-to
      pregnancy, TTP) among survivors who had become pregnant, tried to become
      pregnant, or who had been sexually active for over 2 months without using
      contraception at any time following ABVD. The cumulative incidence of pregnancy
      was calculated using the Kaplan-Meier method. Cox proportional hazards models
      were constructed to compare the pregnancy rate among HL survivors to that
      reported by friend or sibling controls. Thirty-six female HL survivors, who had
      attempted pregnancy after ABVD treatment, and 29 controls, completed the survey.
      Eighteen patients (50%) received 2-4 cycles of ABVD, 16 (44%) received 4-6
      cycles, and 2 (6%) received >6 cycles. The median TTP among both HL survivors and
      controls was 2.0 months. The 12-month pregnancy rates were 70% and 75%,
      respectively. The fertility ratio (FR) for HL survivors versus controls was 0.94
      (95%CI = 0.53-1.66; p = 0.84) after adjusting for age and frequency of
      intercourse (where FR < 1 indicates subfertility). Age at treatment and the
      number of cycles of chemotherapy were not associated with pregnancy rate among HL
      survivors. Female HL patients who had survived without recurrence > or =3 years
      and who had attempted pregnancy after ABVD did not experience significant sub
      fertility.

PMID- 17036378
TI  - Heavy smoking and liver.
AB  - Smoking causes a variety of adverse effects on organs that have no direct contact
      with the smoke itself such as the liver. It induces three major adverse effects
      on the liver: direct or indirect toxic effects, immunological effects and
      oncogenic effects. Smoking yields chemical substances with cytotoxic potential
      which increase necro-inflammation and fibrosis. In addition, smoking increases
      the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that
      would be involved in liver cell injury. It contributes to the development of
      secondary polycythemia and in turn to increased red cell mass and turnover which
      might be a contributing factor to secondary iron overload disease promoting
      oxidative stress of hepatocytes. Increased red cell mass and turnover are
      associated with increased purine catabolism which promotes excessive production
      of uric acid. Smoking affects both cell-mediated and humoral immune responses by
      blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking
      also increases serum and hepatic iron which induce oxidative stress and lipid
      peroxidation that lead to activation of stellate cells and development of
      fibrosis. Smoking yields chemicals with oncogenic potential that increase the
      risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are
      independent of viral infection as well. Tobacco smoking has been associated with
      suppression of p53 (tumour suppressor gene). In addition, smoking causes
      suppression of T-cell responses and is associated with decreased surveillance for
      tumour cells. Moreover, it has been reported that heavy smoking affects the
      sustained virological response to interferon (IFN) therapy in hepatitis C
      patients which can be improved by repeated phlebotomy. Smoker's syndrome is a
      clinico-pathological condition where patients complain of episodes of facial
      flushing, warmth of the palms and soles of feet, throbbing headache, fullness in
      the head, dizziness, lethargy, prickling sensation, pruritus and arthralgia.

PMID- 17036377
TI  - Gene therapy of liver cancer.
AB  - The application of gene transfer technologies to the treatment of cancer has led
      to the development of new experimental approaches like gene directed enzyme/pro
      drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor
      genes. In addition, gene therapy has a big impact on other fields like cancer
      immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are
      being evaluated for the treatment of primary and metastatic liver cancer and some
      of them have reached clinical phases. We present a review on the basis and the
      actual status of gene therapy approaches applied to liver cancer.

PMID- 17036379
TI  - Recent trends in the epidemiology of inflammatory bowel diseases: up or down?
AB  - Inflammatory bowel disease (IBD) is traditionally considered to be common in the
      Western world, and its incidence has sharply increased since the early 1950s. In
      contrast, until the last decade, low prevalence and incidence rates have been
      reported from other parts of the world including Eastern Europe, South America,
      Asia and the Pacific region. Recent trends indicate a change in the epidemiology
      of IBD with previously low incidence areas now reporting a progressive rise in
      the incidence, while in West European and North American countries the figures
      have stabilized or slightly increased, with decreasing incidence rates for
      ulcerative colitis. Some of these changes may represent differences in diagnostic
      practices and increasing awareness of the disease. The quality of studies is also
      variable. Additional epidemiologic studies are needed to better define the burden
      of illness, explore the mechanism of association with environmental factors, and
      identify new risk factors.

PMID- 17036380
TI  - Elevated risk for gastric adenocarcinoma can be predicted from histomorphology.
AB  - The number of patients with gastric cancer has more than doubled since 1985 in
      developing countries. Thus, the questions of whether it can be predicted from
      gastritis morphology, who is at risk and who has a lower risk of developing
      gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations,
      carcinoma, mucosa associated lymphoid tissue (MALT)-lymphoma and extragastric
      diseases only in some individuals. The frequency of ulcerations among H pylori
      infected individuals is estimated to be 13%, gastric cancer about 1% and MALT
      lymphoma around 0.1%. In the literature a multistep model from chronic active H
      pylori-infection through multifocal atrophy, intestinal metaplasia, dysplasia
      (intraepithelial neoplasia) and carcinoma has been described. But this model
      cannot be applied to all routine cases. Since risk factors such as metaplasia and
      atrophy are paracancerous rather than precancerous conditions, this raises the
      question whether there is a better morphological marker. Differences in
      topography, grade and activity of Helicobacter gastritis in the antrum and corpus
      might be good markers for identifying those who are at risk of developing gastric
      cancer. It is known that the so-called corpus dominant H pylori gastritis is
      found more frequently among individuals with early and advanced gastric cancer
      and within high risk populations. This is valid both for first-degree relatives
      of gastric cancer patients and for patients with gastric adenoma and hyperplastic
      polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more
      common in patients with advanced and early gastric cancer, first-degree relatives
      of patients with gastric cancer, patients with gastric adenoma and gastric
      hyperplastic polyps. Therefore, all these patients are at risk of developing
      gastric cancer. Next, the question of who is at risk of developing corpus
      dominant gastritis is raised. It appears that patients with a low acid output
      more frequently develop gastric cancer. Eradication therapy is never performed
      too early but probably sometimes too late after the patients pass a "point of no
      return". Large prospective long term studies are necessary to prove this and
      identify new reliable markers for gastric cancer development.

PMID- 17036382
TI  - Management of pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is a rare disease. It refers to a progressive
      disease process within the peritoneum which originates from the appendix or
      ovaries and is characterised by the production of copious amounts of mucinous
      fluid resulting in a "jelly belly". If untreated the condition is fatal. The
      traditional approach to PMP is based on repeated surgical debulking procedures,
      often associated with intraperitoneal or systemic chemotherapy. The natural
      history of this disease has been drastically modified since the introduction of a
      new surgical approach defined as a peritonectomy procedure. This paper is to
      review the literature on this treatment strategy.

PMID- 17036383
TI  - Total plasma homocysteine and methylenetetrahydrofolate reductase C677T
      polymorphism in patients with colorectal carcinoma.
AB  - AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its
      most common genetic determinant defect, the methylenetetrahydrofolate reductase
      C677T (C677TMTHFR) polymorphism in patients with early stage colorectal
      carcinoma. METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for
      C677TMTHFR substitution was performed by PCR and restriction analysis. RESULTS:
      The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism
      did not differ between the groups. The mean tHcy was statistically higher in
      cancer patients than in control subjects carrying the same C/C or C/T genotype,
      whereas there was no difference in the T/T homozygous carriers of the two groups.
      tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T
      genotype carriers. CONCLUSION: The statistically significant increase of tHcy
      observed in C/C and C/T genotype carriers among our cancer patients is related to
      substrate consumption dependent on the tumor cell proliferation rate, whereas the
      tHcy increase observed in T/T genotype carriers of both groups probably depends
      on the enzymatic deficit of the homocysteine conversion to methionine and/or on
      the folate deficiency.

PMID- 17036381
TI  - Indications for 5-aminosalicylate in inflammatory bowel disease: is the body of
      evidence complete?
AB  - Mesalazine is a safe drug, although adverse events may be seen in a minority of
      patients. This applies also to pregnant women and children. The role of
      mesalazine in combination therapy to improve efficacy and concomitant drug
      pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)
      related colonic carcinoma has not yet been completely elucidated. Therapeutic
      success of mesalazine may be optimized by a combination of high dose and low
      frequency of dosage to improve compliance. Therefore, due to its superior safety
      profile and pharmacokinetic characteristics, mesalazine is preferable to
      sulphasalazine. This paper reviews the literature concerning mechanisms of
      action, indications and off-label use, pharmacokinetic properties and
      formulations, therapeutic efficacy, compliance, paediatric indications,
      chemoprevention, and safety issues and adverse event profile of mesalazine
      treatment versus sulphasalazine. It also highlights these controversies in order
      to clarify the potential benefits of mesalazines in IBD therapy and evidence for
      its use.

PMID- 17036384
TI  - Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are
      associated with altered FasL and perforin cytotoxic pathways.
AB  - AIM: To analyze the level of apoptosis in different mucosal compartments and the
      differential expression of Fas/Fas-ligand and perforin in H pylori-associated
      gastric ulcer. METHODS: Antral specimens from patients with H pylori-related
      active gastric ulcer (GU), H pylori-related gastritis, and non-infected controls
      were analysed for densities and distribution of apoptotic cells determined by the
      TdT-mediated dUDP-biotin nick-end-labelling method. GU patients were submitted to
      eradication therapy with follow-up biopsy after 60 d. Fas, FasL, and perforin
      expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20
      and anti-CD68 by double immunofluorescence and confocal microscopy. Quantitative
      analysis was performed using a computer-assisted image analyser. RESULTS: H
      pylori-infected antrum showed greater surface epithelial apoptosis which
      decreased after eradication therapy. In the lamina propria, higher rates of
      mononuclear cell apoptosis were observed in H pylori-gastritis. Co-expression of
      Fas with T-cell and macrophage markers was reduced in GU. FasL- and perforin
      expressing cells were increased in H pylori-infection and correlated with
      epithelial apoptosis. Perforin-expressing cells were also increased in GU
      compared with H pylori-gastritis. CONCLUSION: Epithelial apoptosis is increased
      in H pylori-infection and correlates to FasL- and perforin-expression by T cells.
      Expression of perforin is correlated with the tissue damage, and may represent
      the enhancement of a distinct cytotoxic pathway in GU. Increased expression of
      FasL not paralleled by Fas on T-cells and macrophages may indicate a reduced
      susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells in H pylori
      infection.

PMID- 17036385
TI  - An herbal formula, CGX, exerts hepatotherapeutic effects on dimethylnitrosamine
      induced chronic liver injury model in rats.
AB  - AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified
      traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)
      induced chronic liver injury model in rats. METHODS: Liver injuries were induced
      in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days
      per week for 4 wk. The rats were administered with CGX (po, 100 or 200 mg/kg per
      day) or distilled water as a control daily for 4 wk starting from the 15(th) d of
      the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and
      ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver
      tissues were analyzed. In addition, gene expression of TNF-alpha, TGF-beta, TIMP
      1, TIMP-2, PDGF-beta, and MMP-2, all of which are known to be associated with
      liver fibrosis, were analyzed using real-time PCR. RESULTS: CGX administration
      restored the spleen weight to normal after having been increased by DMN
      treatment. Biochemical analysis of the serum demonstrated that CGX significantly
      decreased the serum level of ALP (P < 0.05), ALT (P < 0.01), and AST (P < 0.01)
      that had been elevated by DMN treatment. CGX administration moderately lowered
      lipid peroxide production and markedly lowered hydroxyproline generation caused
      by DMN treatment in accordance with histopathological examination. DMN treatment
      induced a highly up-regulated expression of TNF-alpha, TGF-beta, TIMP-1, TIMP-2,
      PDGF-beta, and MMP-2. Of these, the gene expression encoding PDGF-beta and MMP-2
      was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and
      was remarkably ameliorated by CGX administration. CONCLUSION: CGX exhibits
      hepatotherapeutic proper-ties against chronic hepatocellular destruction and
      consequential liver fibrosis.

PMID- 17036387
TI  - Role of vasoactive intestinal peptide and nitric oxide in the modulation of
      electroacupucture on gastric motility in stressed rats.
AB  - AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide
      (VIP) and nitric oxide (NO) in the modulation of electroacupucture (EA) on
      gastric motility in restrained-cold stressed rats. METHODS: An animal model of
      gastric motility disorder was established by restrained-cold stress. Gastric
      myoelectric activities were recorded by electrogastroenterography (EGG). VIP and
      NO concentrations in plasma and gastric mucosal and bulb tissues were detected by
      radioimmunoassay (RIA). VIP expression in the gastric walls was assayed using
      avidin-biotin-peroxidase complex (ABC) and image analysis. RESULTS: In cold
      restrained stressed rats, EGG was disordered and irregular. The frequency and
      amplitude of gastric motility were higher than that in control group (P < 0.01).
      VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously
      decreased (P < 0.01). Following EA at "Zusanli" (ST36), the frequency and
      amplitude of gastric motility were obviously lowered (P < 0.01), while the levels
      of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P
      < 0.01, P < 0.05) and expression of VIP in antral smooth muscle was elevated
      significantly (P < 0.01) in comparison with those of model group. CONCLUSION: VIP
      and NO participate in the modulatory effect of EA on gastric motility. EA at
      "Zusanli" acupoint (ST36) can improve gastric motility of the stressed rats by
      increasing the levels of VIP and NO.

PMID- 17036386
TI  - Hydrodynamics based transfection in normal and fibrotic rats.
AB  - AIM: Hydrodynamics based transfection (HBT), the injection of a large volume of
      naked plasmid DNA in a short time is a relatively simple, efficient and safe
      method for in vivo transfection of liver cells. Though used for quite some time,
      the mechanism of gene transfection has not yet been elucidated. METHODS: A
      luciferase encoding plasmid was injected using the hydrodynamics based procedure
      into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and
      transmission electron microscopy images were taken. The consequence of a dual
      injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an
      anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior
      to the hydrodynamic injection. RESULTS: Large endothelial gaps formed as soon as
      10' following hydrodynamic injection; these gradually returned to normal 10 d
      post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to
      moderate injection of plasmid did not result in efficient transfection suggesting
      that endothelial gaps by themselves are not sufficient for gene expression. Gene
      transfection following hydrodynamic injection in thioacetamide induced fibrotic
      rats was diminished coinciding with the level of fibrosis. Halofuginone, a
      specific collagen type I inhibitor, alleviated this effect. CONCLUSION: The
      hydrodynamic pressure formed following HBT results in the formation of large
      endothelial gaps. These gaps, though important in the transfer of DNA molecules
      from the blood to the space of Disse are not enough to provide the appropriate
      conditions for hepatocyte transfection. Hydrodynamics based injection is
      applicable in fibrotic rats provided that ECM load is reduced.

PMID- 17036388
TI  - The timing of bowel preparation before colonoscopy determines the quality of
      cleansing, and is a significant factor contributing to the detection of flat
      lesions: a randomized study.
AB  - AIM: To compare the cleansing quality of polyethylene glycol electrolyte solution
      and sodium phosphate with different schedules of administration, and to evaluate
      whether the timing of the administration of bowel preparation affects the
      detection of polyps. METHODS: One hundred and seventy-seven consecutive
      outpatients scheduled for colonoscopy were randomized in one of four groups to
      receive polyethylene glycol electrolyte solution or oral sodium phosphate with
      two different timing schedules. Quality of cleansing, polyp detection, and
      tolerance were evaluated. RESULTS: Patients receiving polyethylene glycol or
      sodium phosphate on the same day as the colonoscopy, obtained good to excellent
      global cleansing scores more frequently than patients who received polyethylene
      glycol or sodium phosphate on the day prior to the procedure (P < 0.001). Flat
      lesions, but not flat adenomas, were more frequent in patients prepared on the
      same day (P = 0.02). CONCLUSION: The quality of colonic cleansing and the
      detection of flat lesions are significantly improved when the preparation is
      taken on the day of the colonoscopy.

PMID- 17036389
TI  - Abnormalities of uterine cervix in women with inflammatory bowel disease.
AB  - AIM: To evaluate the prevalence of abnormalities of the uterine cervix in women
      with inflammatory bowel disease (IBD) when compared to healthy controls. METHODS:
      One hundred and sixteen patients with IBD [64 with Crohn's disease (CD) and 52
      with ulcerative colitis (UC)] were matched to 116 healthy controls by age (+/- 2
      years) at the time of most recent papanicolaou (Pap) smear. Data collected
      consisted of age, race, marital status, number of pregnancies,
      abortions/miscarriages, duration and severity of IBD, Pap smear results within
      five years of enrollment, and treatment with immunosuppressive drugs. Pap smear
      results were categorized as normal or abnormal including atypical squamous cells
      of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion
      (LGSIL), and high-grade squamous intraepithelial lesion (HGSIL). RESULTS: The
      median age at the time of Pap smear was 46 (range: 17-74) years for the IBD group
      and matched controls (range: 19-72 years). There were more Caucasian subjects
      than other ethnicities in the IBD patient group (P = 0.025), as well as fewer
      abortions (P = 0.008), but there was no significant difference regarding marital
      status. Eighteen percent of IBD patients had abnormal Pap smears compared to 5%
      of controls (P = 0.004). Subgroup analysis of the IBD patients revealed no
      significant differences between CD and UC patients in age, ethnicity, marital
      status, number of abortions, disease severity, family history of IBD, or disease
      duration. No significant difference was observed in the number of abnormal Pap
      smears or the use of immunosuppressive medications between CD and UC patients (P
      = 0.793). No definitive observation could be made regarding HPV status, as this
      was not routinely investigated during the timeframe of our study. CONCLUSION:
      Diagnosis of IBD in women is related to an increased risk of abnormal Pap smear,
      while type of IBD and exposure to immunosuppressive medications are not. This has
      significant implications for women with IBD in that Pap smear screening protocols
      should be conscientiously followed, with appropriate investigation of abnormal
      results.

PMID- 17036390
TI  - Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis.
AB  - AIM: To report a case of severe idiopathic gastroparesis in complete absence of
      Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue
      from a patient with severe idiopathic gastroparesis unresponsive to medical
      treatment and requiring surgery was analyzed by conventional histology and
      immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor
      had completely disappeared while the local level of stem cell factor, the
      essential ligand for its development and maintenance, was increased. No signs of
      cell death were observed in the pacemaker region. CONCLUSION: These results are
      consistent with the hypothesis that a lack of Kit expression may lead to impaired
      functioning of ICC. Total gastrectomy proves to be curative.

PMID- 17036391
TI  - Polaprezinc protects human colon cells from oxidative injury induced by hydrogen
      peroxide: relevant to cytoprotective heat shock proteins.
AB  - AIM: To investigate the effect of polaprezinc on cellular damage induced by
      hydrogen peroxide (H(2)O(2)) in human colon CaCo2 cells. METHODS: CaCo2 cells
      were treated with polaprezinc (10-100 micromol/L) for 6 h. After polaprezinc
      treatment, the cells were incubated with H(2)O(2) (20 micromol/L) for 1 h. Cell
      viability was measured by MTT assay. Western blot analysis for heat shock protein
      (HSP) 27 and HSP72 in the cells was performed. Moreover, cells were pretreated
      with quercetin (200 micromol/L), an inhibitor of HSP synthesis, 2 h before
      polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were
      assessed in these cells. RESULTS: Polaprezinc significantly protected CaCo2 cells
      from cell damage induced by H(2)O(2), and up-regulated the expressions of HSP27
      and HSP72 in the cells (10, 30 and 100 micromol/L of polaprezinc; 35.0% +/- 7.7%,
      58.3% +/- 14.6% and 64.2% +/- 8.2%, respectively. P < 0.01 versus polaprezinc
      nontreated cells; 6.0% +/- 4.4%). Quercetin inhibited the up-regulation of HSP27
      and HSP72 by polaprezinc and diminished the protective effect of polaprezinc
      against H(2)O(2)-caused injury in the cells. CONCLUSION: Polaprezinc is a useful
      therapeutic agent for treatment of colitis and its effects depend on the function
      of cytoprotective HSP in colon.

PMID- 17036392
TI  - Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2
      in gastrointestinal stromal tumors, leiomyomas and schwannomas.
AB  - AIM: To investigate the role of vascular endothelial growth factor (VEGF) and its
      receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal
      stromal tumors (GISTs). METHODS: Thirty-three GISTs, 15 leiomyomas and 6
      schwannomas were examined by immunohistochemistry in this study. RESULTS: VEGF
      protein was expressed in the cytoplasm of tumor cells, and VEGFR-1 and 2 were
      expressed both in the cytoplasm and on the membrane of all tumors.
      Immunohistochemical staining revealed that 26 GISTs (78.8%), 9 leiomyomas (60.0%)
      and 3 schwannomas (50.0%) were positive for VEGF; 24 GISTs (72.7%), 12 leiomyomas
      (80.0%) and 4 schwannomas (66.7%) were positive for VEGFR-1; 30 GISTs (90.9%), 5
      leiomyomas (33.3%) and 4 schwannomas (66.7%) were positive for VEGFR-2. VEGFR-2
      expression was statistically different between GISTs and leiomyomas (P < 0.0001).
      However, there was no correlation between the expression of VEGF pathway
      componenets and the clinical risk categories. CONCLUSION: Our results suggest
      that the VEGF pathway may play an important role in the differentiation of GISTs,
      leiomyomas and schwannomas.

PMID- 17036393
TI  - Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile.
AB  - AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous
      cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the
      northern and southern ends of the continent, respectively. METHODS: We examined
      47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and
      Chile, respectively. HPV was detected using GP5+/GP6+ primer pair for PCR, and
      confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment
      was used to identify HPV genotype. In addition, P16(INK4A) protein immunostaining
      of all the specimens was conducted. RESULTS: HPV was detected in 21 ESCC
      specimens (29%). Sequencing analysis of L1 region fragment identified HPV-16
      genome in 6 Colombian cases (13%) and in 5 Chilean cases (19%). HPV-18 was
      detected in 10 cases (21%) in Colombia but not in any Chilean case. Since Chilean
      ESCC cases had a higher prevalence of HPV-16 (without statistical significance),
      but a significantly lower prevalence of HPV-18 than in Colombian cases (P =
      0.011) even though the two countries have similar ESCC incidence rates, the
      frequency of HPV-related ESCC may not be strongly affected by risk factors
      affecting the incidence of ESCC. HPV-16 genome was more frequently detected in
      p16 positive carcinomas, although the difference was not statistically
      significant. HPV-18 detection rate did not show any association with p16
      expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but
      the association was not statistically significant. HPV genotypes other than HPV
      16 or 18 were not detected in either country. CONCLUSION: HPV-16 and HPV-18
      genotypes can be found in ESCC specimens collected from two South American
      countries. Further studies on the relationship between HPV-16 presence and p16
      expression in ESCC would aid understanding of the mechanism underlying the
      presence of HPV in ESCC.

PMID- 17036394
TI  - Expression of beta2-integrin on leukocytes in liver cirrhosis.
AB  - AIM: To analyze beta2-integrin expression on blood leukocytes in liver cirrhosis.
      METHODS: In 40 patients with liver cirrhosis and 20 healthy individuals, the
      evaluation of expression of CD11a (LFA-1alpha), CD11b (Mac-1alpha), CD11c
      (alphaX) and CD49d (VLA-4alpha) on peripheral blood leukocytes was performed
      using flow cytometry. The analysis was carried out in groups of patients divided
      into B and C according to Child-Pugh's classification. RESULTS: An increased
      CD11a, CD11b, CD11c and CD49d integrin expression was observed on peripheral
      blood leukocytes in liver cirrhosis. The integrin levels were elevated as the
      advancement of liver failure progressed. The highest expression of integrins
      occurred predominantly on monocytes. A slight expression of VLA-4 was found on
      lymphocytes and granulocytes and it increased together with liver failure. A
      positive correlation was noted between median intensity of fluorescence (MIF)
      expression on polymorphonuclear cells of CD11a and CD11c and CD49d (r = 0.42, P <
      0.01; r = 053, P < 0.01, respectively) in liver cirrhosis stage C. However, no
      correlation was observed between integrin expression on leukocytes. The
      concentrations of sICAM-1, sVCAM-1, and TNFalpha, were significantly elevated in
      liver cirrhosis. CONCLUSION: beta2-integrin expression on leukocytes increases in
      liver cirrhosis decompensated as the stage of liver failure increases, which is a
      result of permanent activation of leukocytes circulating through the inflamed
      liver environment. beta2-integrin expression on circulating leukocytes can
      intensify liver cirrhosis.

PMID- 17036395
TI  - Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty
      liver disease.
AB  - AIM: To analyze the protein expression essential for apoptosis in liver
      steatosis. METHODS: The expression of proapoptotic proteins p53, Bax, and
      antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis
      (NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver
      disease (NAFLD). RESULTS: Immunohistochemical staining of liver tissue showed the
      activation of p53 protein in SH and NSH with increased liver steatosis,
      diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was
      found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P
      < 0.01) and NSH (r = 0.49, P < 0.01). The antiapoptotic protein Bcl-2 was
      diminished together with the advancement of liver steatosis, especially in non
      steatosed hepatocytes (r = 0.43, P < 001). CONCLUSION: Apoptosis is one of the
      most important mechanisms leading to hepatocyte elimination in NAFLD. The
      intensification of inflammation in NAFLD induces proapoptotic protein p53 with
      the inhibition of antiapoptotic Bcl-2.

PMID- 17036396
TI  - Aggressive treatment of acute anal fissure with 0.5% nifedipine ointment prevents
      its evolution to chronicity.
AB  - AIM: To investigate the efficacy of topical application of 0.5% nifedipine
      ointment in healing acute anal fissue and preventing its progress to chronicity.
      METHODS: Thirty-one patients (10 males, 21 females) with acute anal fissure from
      September 1999 to January 2005 were treated topically with 0.5% nifedipine
      ointment (t.i.d.) for 8 wk. The patients were encouraged to follow a high-fiber
      diet and assessed at 2, 4 and 8 wk post-treatment. The healing of fissure and any
      side effects were recorded. The patients were subsequently followed up in the
      outpatient clinic for one year and contacted by phone every three months
      thereafter, while they were encouraged to come back if symptoms recurred.
      RESULTS: Twenty-seven of the 31 patients completed the 8-wk treatment course, of
      them 23 (85.2%) achieved a complete remission indicated by resolution of symptoms
      and healing of fissure. Of the remaining four unhealed patients (14.8%), 2 opted
      to undergo lateral sphincterotomy and the other 2 to continue therapy for four
      additional weeks, resulting in healing of fissure. All the 25 patients with
      complete remission had a mean follow-up of 22.9 +/- 14 (range 6-52) mo.
      Recurrence of symptoms occurred in four of these 25 patients (16%) who were
      successfully treated with an additional 4-wk course of 0.5% nifedipine ointment.
      Two of the 27 (7.4%) patients who completed the 8-wk treatment presented with
      moderate headache as a side effect of nifedipine. CONCLUSION: Topical 0.5%
      nifedipine ointment, used as an agent in chemical sphincterotomy, appears to
      offer a significant healing rate for acute anal fissure and might prevent its
      evolution to chronicity.

PMID- 17036397
TI  - Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and
      increased expression in individuals from northern Brazil with gastric
      adenocarcinoma.
AB  - AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene
      alterations and its expression in gastric cancer and to correlate these findings
      with histopathological characteristics of gastric tumors. METHODS: Specimens were
      collected surgically from seven patients with gastric adenocarcinomas.
      Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH)
      for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases
      showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and
      intestinal histopathological types of Lauren. No significant difference (P <
      0.05) was observed between the level of chromosome 8 ploidy and the site, stage
      or histological type of the adenocarcinomas. C-MYC high amplification, like
      homogeneously stained regions (HSRs) and double minutes (DMs), was observed only
      in the intestinal-type. Structural rearrangement of C-MYC, like translocation,
      was observed only in the diffuse type. Regarding C-MYC gene, a significant
      difference (P < 0.05) was observed between the two histological types. The C-MYC
      protein was expressed in all the studied cases. In the intestinal-type the C-MYC
      immunoreactivity was localized only in the nucleus and in the diffuse type in the
      nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between
      intestinal and diffuse types of gastric tumors support the hypothesis that these
      types follow different genetic pathways.

PMID- 17036398
TI  - Relationship between antioxidant capacity and oxidative stress in children with
      acute hepatitis A.
AB  - AIM: To investigate in children with acute hepatitis A. According to our
      knowledge, there are no data about the blood levels of malondialdehyde (MDA, an
      indicator of oxidative stress) and nonenzymic antioxidants in children with acute
      hepatitis A. METHODS: Whole blood MDA and reduced glutathione (GSH), serum beta
      carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females,
      9 males) children with acute hepatitis A and in 29 (13 females, 16 males) healthy
      control subjects. RESULTS: There was a statistically significant difference
      between patients and controls for all parameters (P < 0.05). Lipid peroxidation
      marker MDA was significantly elevated (P < 0.001), while antioxidants beta
      carotene, retinol and GSH were significantly decreased (all P < 0.001) in
      patients compared to healthy subjects. In addition, alpha-tocopherol and ascorbic
      acid levels were significantly lower in patients when compared to age and sex
      matched controls (P < 0.05, P < 0.01, respectively). CONCLUSION: Our study shows
      that hepatitis A virus induces oxidative stress in children with hepatitis A.
      This finding could be taken into consideration to improve the therapeutic
      approach in acute hepatitis A.

PMID- 17036399
TI  - Evaluation of the use of rapid urease test: Pronto Dry to detect H pylori in
      patients with dyspepsia in several cities in Indonesia.
AB  - AIM: To evaluate Pronto Dry examination in patients with dyspepsia. METHODS: The
      study was conducted in patients with dyspepsia who underwent endoscopic
      examination in several endoscopic centers of several cities in Indonesia from
      January 2003 until April 2004. Biopsies for histopathologic examination were
      fixed with formalin and sent to Histopathologic Department to be analyzed and
      confirm the presence of H pylori infection. If H pylori was found positive, the
      density was calculated semi quantitatively. Histopathologic examination from
      gastric biopsy samples was interpreted based on the updated Sydney system
      classification. RESULTS: Of 550 patients, 309 (56%) were male and 241 (44%) were
      female with ages ranging from 15 to 82 years. Mean age was 44.98 +/- 14.46 years.
      Mean age of male patients was 44.35 +/- 13.85 years and mean age of female
      patients was 45.78 +/- 15.19 years. Evaluation of endoscopic results showed
      gastric ulcer in 36 cases (6.5%) and duodenal ulcer in 20 cases (3.6%). Normal
      endoscopic finding was found in 45 cases (8.2%) and minimal disorder of gastritis
      and duodenitis were found in 246 cases (44.7%). One case of gastric cancer was
      identified. Of 56 cases which were positive based on the criteria used, 39
      patients were positive with Pronto Dry and 17 patients were negative with Pronto
      Dry. Overall sensitivity and specificity of Pronto Dry were 69.7% and 95.7%
      respectively. Positive predictive value was 66.1% and negative predictive value
      was 96.4% and overall accurate rate was 92.9%. CONCLUSION: Pronto Dry seems
      promising as a diagnostic tool to detect H pylori more rapidly and accurately.

PMID- 17036400
TI  - Metastatic breast cancer to the gastrointestinal tract: a case series and review
      of the literature.
AB  - Metastatic breast cancer involving the hepatobiliary tract or ascites secondary
      to peritoneal carcinomatosis has been well described. Luminal gastrointestinal
      tract involvement is less common and recognition of the range of possible
      presentations is important for early and accurate diagnosis and treatment. We
      report 6 patients with a variety of presentations of metastatic breast cancer of
      the luminal gastrointestinal tract. These include oropharyngeal and esophageal
      involvement presenting as dysphagia with one case of pseudoachalasia, a linitis
      plastica-like picture with gastric narrowing and thickened folds, small bowel
      obstruction and multiple strictures mimicking Crohn's disease, and a colonic
      neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of
      breast cancers is more likely to metastasize to the gastrointestinal tract. These
      patients presented with gastrointestinal manifestations after an average of 9.5
      years and as long as 20 years from initial diagnosis of breast cancer. Given the
      increased survival of breast cancer patients with current therapeutic regimes,
      more unusual presentations of metastatic disease, including involvement of the
      gastrointestinal tract can be anticipated.

PMID- 17036401
TI  - Pancreatic cancer with a high serum IgG4 concentration.
AB  - Differentiation between autoimmune pancreatitis and pancreatic cancer is
      sometimes difficult. It has been reported that serum IgG4 concentrations are
      significantly elevated and particularly high (>135 mg/dL) in autoimmune
      pancreatitis. Measurement of serum IgG4 has become a useful tool for
      differentiating between autoimmune pancreatitis and pancreatic cancer. However,
      we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL)
      who underwent pancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4
      levels continued after the resection. On histology, adenocarcinoma of the
      pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the
      lower bile duct and duodenum, but there were no findings of autoimmune
      pancreatitis. Although a small metastasis was detected in one parapancreatic
      lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma
      cells infiltrated the cancerous areas of the pancreas, but only a few IgG4
      positive plasma cells were detected in the noncancerous areas. Pancreatic cancer
      cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive
      plasma cells was detected in the swollen regional lymph nodes and in the duodenal
      mucosa. We believe that the serum IgG4 level was elevated in this patient with
      pancreatic cancer as the result of an IgG4-related systemic disease that had no
      clinical manifestations other than lymphadenopathy.

PMID- 17036402
TI  - Biliary stone causing afferent loop syndrome and pancreatitis.
AB  - We report the case of an 84-year-old female who had a partial gastrectomy with
      Billroth-II anastomosis 24 years ago for a benign peptic ulcer who now presented
      an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was
      caused by a gallstone that migrated through a cholecystoenteric fistula. This is
      the first description in the literature of a biliary stone causing afferent loop
      syndrome.

PMID- 17036403
TI  - Propylthiouracyl-induced severe liver toxicity: an indication for alanine
      aminotransferase monitoring?
AB  - Propylthiouracyl (PTU)-related liver toxicity is likely to occur in about 1% of
      treated patients. In case of acute or subacute hepatitis, liver failure may occur
      in about one third. We report two further cases of PTU-induced subacute
      hepatitis, in whom the delay between occurrence of liver damage after the
      initiation of treatment, the underestimation of its severity and the delayed
      withdrawal of the drug were all likely responsible for liver failure. The high
      incidence of liver toxicity related to PTU, its potential severity and delayed
      occurrence after initiation of treatment are in favor of monthly alanine
      aminotransferase monitoring, at least during the first six months of therapy.

PMID- 17036404
TI  - Acute coronary syndrome after infliximab therapy in a patient with Crohn's
      disease.
AB  - Infliximab is a potent anti-TNF antibody, which is used with great success in
      Crohn's disease patients. Since its release in clinical practice, several adverse
      reactions have been observed. The interest in possible consequences of its
      administration is still high because of the recent introduction of the drug for
      the long-term maintenance therapy of refractory luminal and fistulizing Crohn's
      disease. We present a case of acute coronary syndrome (non-STEMI) in a patient
      with corticoid resistant Crohn's disease after his first dose of infliximab. By
      reviewing the scant articles that exist in the literature on this topic we made
      an effort to delineate the possible mechanisms of this phenomenon.

PMID- 17036405
TI  - A case of solid pseudopapillary tumor of the pancreas.
AB  - We present ultrasound, computed tomography and magnetic resonance imaging
      findings in a case with pancreatic solid pseudopapillary tumor and their
      correlations with histopathology. Ultrasound revealed a hypoechogenic mass, and
      computed tomography revealed a hypodense mass at the pancreatic head minimally
      enhanced after intravenous contrast agent administration. Magnetic resonance
      imaging showed a hypointense mass on unenhanced T1-weighted images including a
      hyperintense focus representing the hemorrhage. The lesion was hyperintense on T2
      weighted images. On the postcontrast images the lesion showed peripheral thin
      contrast enhancement in arterial phase and enhanced slightly diffusely in venous
      and equilibrium phases. The patient underwent elective resection of the mass and
      pancreatoduodenectomy with jejunostomy tube placement. A final diagnosis of solid
      pseudopapillary tumor was made histopathologically. Solid pseudopapillary tumor
      is a rare pancreatic tumor. It is important to make the diagnosis preoperatively
      because with an adequate surgical resection the prognosis is good. A
      multimodalitary approach, especially magnetic resonance imaging can suggest the
      diagnosis without the need for biopsy.

PMID- 17036406
TI  - CR1/160--Invasive pulmonary aspergillosis in immuno-compromised children with
      leukemia.

PMID- 17036407
TI  - CR3/108--Congenital alveolar capillary dysplasia with familiary microphthalmia.

PMID- 17036408
TI  - CR5/20--Acute renal failure in a child with cystic fibrosis awaiting lung
      transplantation--a good outcome after all.

PMID- 17036409
TI  - CR8-194--A case of fulminated fatal disseminated Varicella Zoster virus infection
      with severe pulmonary damage.

PMID- 17036410
TI  - CR10/80--Lymphoid interstitial pneumonia and Kabuki-Syndrome in a young man.

PMID- 17036411
TI  - Mayo Clinic offers new genetic test to screen for side effects of antidepressant
      treatment.

PMID- 17036412
TI  - CR12/339--Nebulized cidofovir for recurrent respiratory papillomatosis: a case
      report.

PMID- 17036413
TI  - Whole-blood thiopurine S-methyltransferase activity with genotype concordance: a
      new, simplified phenotyping assay.
AB  - BACKGROUND: We have developed a new thiopurine S-methyltransferase (TPMT)
      phenotyping method that measures TPMT activity in whole blood. To evaluate this
      assay, we compared it with conventional TPMT phenotyping, which uses a red blood
      cell (RBC) lysate and genotyping for analysis of common TPMT mutations. METHODS:
      Whole-blood and RBC lysates were prepared from 402 patients' samples received for
      routine analysis. The TPMT activity of lysates was determined using 6-thioguanine
      as substrate with high-performance liquid chromatographic (HPLC) analysis and
      fluorimetric detection. DNA was extracted from buffy coats using phenol
      chloroform extraction. A multiplex amplification refractory mutation system
      (ARMS) strategy was used to screen for the common TPMT mutations TPMT*2 and
      TPMT*3 (TPMT*3A, TPMT*3C and TPMT*3D). RESULTS: TPMT activities were higher in
      the whole-blood (mean TPMT activity 51 nmol 6-MTG/gHb/h) compared with the RBC
      lysate (37 nmol 6-MTG/gHb/h). Overall, concordance with TPMT genotypic analysis
      was 97% for both the new whole-blood and standard RBC lysate methods. Between low
      TPMT activity and heterozygotes, both phenotypic methods gave a concordance of
      79%. CONCLUSION: Using multiplex ARMS testing for TPMT*2 and 3*C mutations to
      define the cut-off between low and normal TPMT activity, we have demonstrated
      that the new whole-blood TPMT phenotyping method performs as well as the
      conventional RBC lysate assay. This new method overcomes the need to prepare a
      RBC lysate, a process which is time consuming and increases analytical variation.
      The resulting assay is better suited to a regional or national TPMT phenotyping
      service.

PMID- 17036415
TI  - Pre-exposure prophylaxis effective.

PMID- 17036414
TI  - Calculated free testosterone in men: comparison of four equations and with free
      androgen index.
AB  - BACKGROUND: Serum testosterone remains the most important investigation in the
      diagnosis of androgen deficiency in men. Most of the circulating testosterone is
      bound to albumin and sex hormone-binding globulin (SHBG), whereas free
      testosterone accounts for approximately 2% of total testosterone. Because direct
      measurement of free testosterone is impractical in routine practice, several
      equations are used to provide clinically useful estimates of free testosterone
      concentration. This study aimed to (1) obtain locally derived reference limits
      for total testosterone and calculated free testosterone (CFT) concentrations, and
      (2) critically evaluate the equations commonly used to estimate free
      testosterone. METHODS: Serum total testosterone, SHBG and albumin were assayed in
      morning blood samples obtained from 126 healthy men (aged 20-45 years) known to
      have normal semen analysis. CFT concentrations calculated using four published
      methods (i.e. the Sodergard, Nanjee-Wheeler, Vermeulen and Ly-Handelsman
      equations) were compared with one another and the free androgen index. RESULTS:
      Reference intervals for total testosterone and CFT by the Vermeulen equation were
      9.4-31.0 nmol/L and 0.245-0.785 nmol/L (2.5-97.5 percentile), respectively. CFT
      values varied considerably with the four equations examined. Mean biases ranged
      from 5.8 to 56.0%; the Nanjee-Wheeler and Ly-Handelsman equations yielded
      positive and negative biases, respectively, against the other equations. Free
      androgen index was shown to correlate poorly with CFT (r2=0.21-0.46) and over
      estimate the CFT at low SHBG concentrations. CONCLUSIONS: We have used various
      equations to derive reference ranges for CFT in healthy men aged 20-45 years. We
      suggest that CFT be incorporated into the investigation regimen for suspected
      hypogonadism when total testosterone results are equivocal.

PMID- 17036416
TI  - Media crucial to AIDS fight.

PMID- 17036417
TI  - Routine, voluntary testing urged.

PMID- 17036419
TI  - [Third-country physicians].

PMID- 17036418
TI  - Radiculopathy and the herniated lumbar disc. Controversies regarding
      pathophysiology and management.

PMID- 17036420
TI  - [Oxytetral and Lindynette].

PMID- 17036421
TI  - Valuing health.

PMID- 17036422
TI  - Ethical clinical practice and sport psychology: when two worlds collide.
AB  - From their own practices, the authors offer insight into potential ethical
      dilemmas that may frequently develop in an applied psychology setting in which
      sport psychology is also being practiced. Specific ethical situations offered for
      the reader's consideration include confidentiality with coaches, administration,
      parents, and athlete-clients; accountability in ethical billing practices and
      accurate diagnosing; identification of ethical boundaries in nontraditional
      practice settings (locker room, field, rink, etc.); and establishment of
      professional competence as it relates to professional practice and marketing.

PMID- 17036423
TI  - Medicare, the national quality infrastructure, and health disparities.
AB  - What can Medicare do to improve quality and reduce disparities in clinical care?
      Increasing the cultural competence of individual physicians and their use of
      evidence-based guidelines will be useful--but insufficient. What is needed are
      organized care management processes that will support physicians and medical
      teams in their clinical decision-making, assist patients in managing their own
      illnesses, and provide clinicians with feedback on their performance. Medicare
      should therefore seek to strengthen both the capabilities of medical groups to
      improve the quality of care and their incentives to do so. Unless carefully
      designed, however, incentives to improve quality--such as pay for performance and
      public reporting--could increase disparities, for example, by directing
      additional resources to providers who are already performing at a high level.
      Medicare should be alert to this possibility when devising incentives for quality
      and should carefully study the effects of incentives on disparities. If general
      efforts at quality improvement do not succeed in reducing disparities, targeted
      measures will be required.

PMID- 17036424
TI  - Ethical issues in exercise psychology.
AB  - Exercise psychology encompasses the disciplines of psychiatry, clinical and
      counseling psychology, health promotion, and the movement sciences. This emerging
      field involves diverse mental health issues, theories, and general information
      related to physical activity and exercise. Numerous research investigations
      across the past 20 years have shown both physical and psychological benefits from
      physical activity and exercise. Exercise psychology offers many opportunities for
      growth while positively influencing the mental and physical health of
      individuals, communities, and society. However, the exercise psychology
      literature has not addressed ethical issues or dilemmas faced by mental health
      professionals providing exercise psychology services. This initial discussion of
      ethical issues in exercise psychology is an important step in continuing to move
      the field forward. Specifically, this article will address the emergence of
      exercise psychology and current health behaviors and offer an overview of ethics
      and ethical issues, education/training and professional competency, cultural and
      ethnic diversity, multiple-role relationships and conflicts of interest,
      dependency issues, confidentiality and recording keeping, and advertisement and
      self-promotion.

PMID- 17036425
TI  - Re: New generation open-bite treatment with zygomatic anchorage. Angle Orthod.
      2006; 76: 519-526.

PMID- 17036426
TI  - Re: Failure rate of self ligating and edgewise brackets bonded with conventional
      acid etching and a self etching primer: a prospective in vivo study. Angle
      Orthod. 2006; 76: 119-122.

PMID- 17036427
TI  - Improving Medicare's data on race and ethnicity.
AB  - Medicare's databases provide a rich source of information about the program's 43
      million beneficiaries. These data have played an important role in documenting
      racial, ethnic, and socioeconomic disparities in health and health care. Because
      they derive largely from administrative records that have been collected over
      many years using varying standards, however, they are not fully adequate for
      monitoring and reducing disparities. The Centers for Medicare & Medicaid Services
      (CMS) has supported a number of initiatives to improve the quality of its data on
      race and ethnicity. Yet analyses of 2002 Medicare administrative data show that
      only 52 percent of Asian beneficiaries and 33 percent of both Hispanic and
      American Indian/Alaska Native beneficiaries were identified correctly. As CMS
      moves to reduce disparities, and as researchers strive to explain how and why
      disparities occur, further improvements in Medicare's data are essential. Health
      care organizations also need data on the race and ethnicity of the people they
      serve in order to improve the quality of care for minorities. This brief provides
      some recommendations for further efforts.

PMID- 17036428
TI  - Health care need: three interpretations.
AB  - The argument that scarce health care resources should be distributed so that
      patients in 'need' are given priority for treatment is rarely contested. In this
      paper, we argue that if need is to play a significant role in distributive
      decisions it is crucial that what is meant by need can be precisely articulated.
      Following a discussion of the general features of health care need, we propose
      three principal interpretations of need, each of which focuses on separate
      intuitions. Although this account may not be a completely exhaustive reflection
      of what people mean when they refer to need, the three interpretations provide a
      starting-point for further debate of what the concept means in its specific
      application. We discuss combined interpretations, the meaning of grading needs,
      and compare needs-based priority setting to social welfare maximisation.

PMID- 17036429
TI  - Behavioural genetics: why eugenic selection is preferable to enhancement.
AB  - Criminal behaviour is but one behavioural tendency for which a genetic influence
      has been suggested. Whilst this research certainly raises difficult ethical
      questions and is subject to scientific criticism, one recent research project
      suggests that for some families, criminal tendency might be predicted by
      genetics. In this paper, supposing this research is valid, we consider whether
      intervening in the criminal tendency of future children is ethically justifiable.
      We argue that, if avoidance of harm is a paramount consideration, such an
      intervention is acceptable when genetic selection is employed instead of genetic
      enhancement. Moreover, other moral problems in avoiding having children with a
      tendency to criminal behaviour, such as the prospect of social discrimination,
      can also be overcome.

PMID- 17036430
TI  - A living will clause for supporters of animal experimentation.
AB  - Many people assume that invasive research on animals is justified because of its
      supposed benefits and because of the supposed mental inferiority of animals.
      However probably most people would be unwilling to sign a living will which
      consigns themselves to live biomedical experimentation if they ever, through
      misfortune, end up with a mental capacity equivalent to a laboratory animal. The
      benefits would be greater by far for medical science if living will signatories
      were to be used, and also the mental superiority boast would no longer apply.
      Ultimately, it is argued that invasive biomedical experiments would be
      unacceptable in a democratic society whose members are philosophically self
      consistent.

PMID- 17036431
TI  - Is the argument from marginal cases obtuse?
AB  - Elizabeth Anderson claims that the argument from marginal cases is 'the central
      argument' behind the claim that nonhuman animals have rights. But she thinks,
      along with Cora Diamond, that the argument is 'obtuse'. Two different meanings
      could be intended here: that the argument from marginal cases is too blunt or
      dull to dissect the reasons why it makes sense to say that nonhuman animals have
      rights or that the argument from marginal cases is insensitive regarding
      nonrational human beings (the marginal cases of humanity). The purpose of the
      present article is to argue that, despite Anderson's and Diamond's nuanced and
      perceptive treatments of the argument from marginal cases, this argument is not
      obtuse in either sense of the term.

PMID- 17036432
TI  - Protecting third parties in human subjects research.

PMID- 17036433
TI  - General clinical research center staff nurse perceptions and behaviors regarding
      informed consent: results of a national survey.

PMID- 17036434
TI  - The problem with optimism in clinical trials.

PMID- 17036435
TI  - Very early pregnancy.

PMID- 17036436
TI  - Commentary on animal rights stirs more debate.

PMID- 17036437
TI  - The informed consent process in a rural African setting: a case study of the
      Kassena-Nankana district of Northern Ghana.

PMID- 17036438
TI  - Protecting human subjects in the NIH's Intramural Research Program: a draft
      instrument to evaluate convened meetings of its IRBs.

PMID- 17036439
TI  - Caregivers as subjects of clinical drug trials: a review of human subjects
      protection practices in published studies of Alzheimer's disease
      pharmacotherapies.

PMID- 17036440
TI  - Expressing freedom and taking liberties: the paradoxes of aberrant science.
AB  - Complete freedom does not exist, despite people's preparedness to die for it.
      Scientific freedom is much defended and yet much misunderstood. Scientists have
      limits imposed on their freedom by the disciplines and discourse communities in
      which they place themselves. Freedom within these socially constructed
      constraints needs to be distinguished from taking liberties with the rules and
      practices that make up these constraints, and validate the activities of special
      groups within society. Scientists (and the public) perceive taking liberties with
      science's rules and practices as aberrant science, and they often react
      punitively. Aberrant science can be broadly examined under four headings: wicked
      science, naughty science, dysfunctional science, and ideologically unacceptable
      science. When we examine examples of perceived aberrant science, we find that
      these categories of "misconduct" are connected and often confused. Scientific
      freedom needs to be redefined with due regard to current understandings of
      scientists as human beings facing powerful social pressures to deliver results of
      a particular kind.

PMID- 17036441
TI  - Prenatal diagnosis and selective abortion: a result of the cultural turn?
AB  - There is a growing trend in obstetric medicine of prenatal diagnosis and the
      selective abortion of foetuses that are likely to be born with a disability.
      Reasons commonly given to explain this trend include the financial implications
      of screening and testing policies, the disruption to families caused by the birth
      of a child with a disability, and the potential quality of life of the unborn
      child. This paper reflects upon another possible reason for this. It is argued
      that it is, in part, a consequence of our attitudes towards disability and a
      pursuit of aesthetic perfection. These attitudes arise from a social context that
      may be explained by considering the effect on the disabled community of the
      transition from modernity to postmodernity. This shift is demonstrated by
      inspecting some of the synonymous developments in art history. It is suggested
      that this "cultural turn" may have both helped and hindered people with
      disabilities, but the hypothesis requires further testing. This could best be
      achieved with a qualitative study of what motivates parental decision making in
      the obstetric unit.

PMID- 17036442
TI  - Medical ethics as therapy.
AB  - In this paper, the author examines a style of teaching for a medical ethics
      course designed for medical students in their clinical years, a style that some
      believe conflicts with a commitment to analytic philosophy. The author discusses
      (1) why some find a conflict, (2) why there really is no conflict, and (3) the
      approach to medical ethics through narratives. The author will also argue that
      basing medical ethics on the use of narratives has problems and dangers not fully
      discussed in the literature.

PMID- 17036443
TI  - Intellectual property and biotechnology: the U.S. internal experience--Part II.
AB  - Continuing the discussion begun in the March 2006 issue of the Kennedy Institute
      of Ethics Journal, this paper further documents the failure of the United States
      to adequately consider possible modifications in the traditional robust system of
      intellectual property rights as applied to biotechnology. It discusses concrete
      suggestions for alternative disclosure requirements, for exemptions for research
      tools, and for improved access to clinical advances. In each of these cases, the
      modifications might be more responsive to the full set of relevant values.

PMID- 17036444
TI  - Academic freedom and academic-industry relationships in biotechnology.
AB  - Commercial academic-industry relationships (AIRs) are widespread in biotechnology
      and have resulted in a wide array of restrictions on academic research.
      Objections to such restrictions have centered on the charge that they violate
      academic freedom. I argue that these objections are almost invariably
      unsuccessful. On a consequentialist understanding of the value of academic
      freedom, they rely on unfounded empirical claims about the overall effects that
      AIRs have on academic research. And on a rights-based understanding of the value
      of academic freedom, they rely on excessively lavish assumptions about the kinds
      of activities that academic freedom protects.

PMID- 17036445
TI  - The ethical limits in expanding living donor transplantation.
AB  - The past decade has witnessed the emergence of novel methods to increase the
      number of living donors. Although such programs are not likely to yield high
      volumes of organs, some transplant centers have gone to great lengths to
      establish one or more of them. I discuss some of the ethical and policy issues
      raised by five such programs: (1) living-paired and cascade exchanges; (2)
      unbalanced living-paired exchanges; (3) list-paired exchanges; (4) nondirected
      donors; and (5) nondirected donors catalyzing cascade exchanges. I argue that
      living-paired and cascade exchanges are ethically sound, but will lead to only a
      few additional transplants. Unbalanced exchanges and list-paired exchanges raise
      ethical issues that should limit their permissibility. Nondirected donations can
      be ethically sound with adherence to strict eligibility criteria and fair
      allocation procedures. Nondirected donors catalyzing cascade exchanges can be
      ethically sound provided that individuals with blood types O and B are not made
      worse off.

PMID- 17036446
TI  - Multiple roles and successes in public bioethics: a response to the public forum
      critique of bioethics commissions.
AB  - National bioethics commissions have been critiqued for a variety of structural,
      procedural, and political aspects of their work. A more recent critique published
      by Dzur and Levin uses political philosophy to constructively critique the work
      of national bioethics commissions as public deliberative forums. However, this
      public forum critique of bioethics commissions ignores empirical research in
      political science and normative claims that suggest that advisory commissions can
      and should have diverse of functions beyond that of being public forums. The
      present paper argues that the public forum critique too narrowly considers the
      roles that bioethics commissions can play in public bioethics and ignores the
      moral obligation of commissions to fulfill their mandates. Evaluations of
      commissions must consider that these institutions can serve in capacities other
      than those of a public deliberative forum and use additional measures to evaluate
      the multiple roles and successes of bioethics commissions in public policy.

PMID- 17036447
TI  - Quality use of medicines and nurses.

PMID- 17036448
TI  - Topic: current issues and challenges in community health.

PMID- 17036449
TI  - The caregiving experience: how much do health professionals understand?
AB  - Legal, social and economic factors have changed the delivery of care to people
      who have a mental disorder. Many of these people are now treated in the community
      and they live with or in close proximity to their family. The aim of this paper
      is to provide health professionals with an insight into the experience of being a
      caregiver to a person with a person with a mental disorder. For these families
      caregiving becomes an integral part of everyday life. Positive outcomes for both
      the caregiver and the ill family member are more likely to occur when effective
      levels of collaboration exist between health professionals and caregivers.
      Collaboration is enhanced when caregivers and health professionals value each
      other's contribution to the ill family member's care. Often the burden, stress,
      and socio-economic effects on the family caring for a person with mental illness
      is not sufficiently appreciated and further increases this burden. A review of
      the literature from the caregiver's perception is presented. An increased
      understanding of the caregiving experience will enable health professionals to
      develop and implement strategies that facilitate positive outcomes for the
      caregiver and the ill family member.

PMID- 17036450
TI  - The trials and tribulations of team-nursing.
AB  - AIM: The aim of this study was to review the team-nursing approach to care
      adopted by two general medical wards in a large private hospital. The delivery
      model of care was reviewed to determine the factors that enhance and/or hinder
      the timely delivery, continuity and communication of care. METHOD: All nursing
      and ancillary staff who worked on two medical wards at a private teaching
      hospital were invited to participate in the study. Thirty eight participants from
      the two wards took part in focus group discussions, individual interviews and
      completed the Staff Continuity of Care Questionnaire. FINDINGS: Findings
      indicated that achieving functionally sound teamwork is a complex task that is
      affected by the interplay of a number of organisational, patient and staff
      factors. Its smooth application is further affected by the uncertain and changing
      conditions on the wards, which are difficult to control and impact on the smooth
      delivery of patient care. The findings revealed strengths and weaknesses in
      teamwork, communication of care, documentation and discharge planning. The
      results also highlighted factors that enhance and hinder the smooth delivery of
      care. This paper details the factors that influence the delivery of care from the
      perspectives of nursing staff and makes recommendations to enhance the delivery
      of patient care using a team-nursing approach.

PMID- 17036451
TI  - Occupational health nursing practice in Australia: what occupational health
      nurses say they do and what they actually do.
AB  - This study investigated current activities of occupational health nurses (OHN) in
      Australia related to the applicability of and their involvement in emergent role,
      wellness-based practices and traditional role and illness-based practices. A
      questionnaire encompassing the eight Areas of Practice as articulated by the
      Australian College of Occupational Health Nursing (ACOHN) competency standards
      was used to obtain data from 93 OHNs affiliated with ACOHN. More traditional role
      Areas of Practice such as treatment services, health assessment and
      rehabilitation services were seen as more applicable to their practice and a
      substantial amount of time was spent on them. Managing occupational health and
      safety (OH&S) service' was the only emergent area that was a substantial part of
      the OHN's role. Less time was devoted to other emergent and pro-active areas of
      OHN practice, such as illness and injury prevention, health promotion, health
      education and research into OH&S. While less time was allocated to emergent Areas
      of Practice, and they were ranked more lowly they were considered to be
      applicable to practice. The findings of this study suggest that OHNs in Australia
      may not be engaging fully in all Areas of Practice that have been articulated by
      the ACOHN, particularly emergent role activities. Although Australian OHNs
      perform all the activities articulated in the ACOHN Areas of Practice, their
      focus is still primarily illness and injury based, and also management. While the
      profession is supportive of emergent role activities, there is a need to debate
      possibilities, undertake research into barriers and supports for emergent role
      activities, more clearly articulate future directions for the OHN role, and
      develop strategies to support OHNs as they develop their professional role.

PMID- 17036452
TI  - A longitudinal study of student and experienced nurses' self-concept.
AB  - Researchers continue to emphasise the importance of professional identity or
      nurses' self-concept in the retention debate, although limited research has been
      undertaken on this specific issue. The purpose of this study was to capitalise
      upon recent advances in self-concept theory and measurement to identify, compare,
      and contrast the development of self-concept for graduate and experienced nurses.
      The Self Description Questionnaire III was used to assess four areas of general
      self-concept and a newly developed Nurses Self-Concept Questionnaire was used to
      assess six domains of self-concept specific to nursing. Student nurses completed
      instrumentation during their final year of a University course (N=506) and 6
      months after graduation (N=110). Experienced nurses completed instrumentation at
      the end of the year (N=528) and eight months later (N=332). The results revealed
      that graduate self-concept was lower than experienced nurse self-concept in most
      domains at initial measurement (Time 1). Whilst some graduate self-concept
      domains demonstrated a rise in mean scores at eight months (Time 2), scores
      remained significantly lower overall than those of experienced nurses. The domain
      of Nurse General Self-Concept had fallen significantly from the student to
      graduate experience. Little change in the self-concept domains occurred over time
      for the experienced nurse group. The results provide valuable empirical evidence
      elucidating the development of nurses' self-concept. Key implications include the
      need to monitor self-concept development in graduate nurses and develop
      strategies for self-concept enhancement particularly for new graduates' Nurse
      General Self-Concept.

PMID- 17036453
TI  - Mentoring matters: developing rural nurses knowledge and skills.
AB  - Mentoring, the alliance of two people with varying degrees of experience in order
      to create opportunities for support and learning, is being encouraged as a
      response to current workforce issues in Australian rural nursing. The nursing
      profession is beginning to recognise the benefits of mentorship in providing
      psychosocial support and role acquisition skills to novice practitioners. These
      outcomes are valuable for enhancing the recruitment and retention of staff. The
      Mentor Development and Support Project of The Association for Australian Rural
      Nurses (AARN), established in 2003, was a strategy for increasing mentoring in
      the rural nursing workforce. This project aimed to develop the capacity of rural
      nurses to mentor effectively, as well as provide support for them for the
      duration of the mentoring partnership. This article reports on aspects of the
      AARN project. It includes a discussion of the need for planned mentor development
      opportunities and provides the rationale for the curriculum content of project
      workshops. It also includes evaluated outcomes for participants in the project.

PMID- 17036454
TI  - Continuing the dialogue: a reply to Bernard Gert.
AB  - Continuing the dialogue begun in the March 2006 issue of the Kennedy Institute of
      Ethics Journal, I suggest that Bernard Gert's response to my paper does not
      adequately address the criticisms I make of his theory's application to bioethics
      cases.

PMID- 17036455
TI  - [The problems of diagnostics, treatment and prevention arrangement in patients of
      therapeutic profile].
AB  - The recent data research from many countries demonstrates that severe and
      sometime irreversible complications as a result of inadequate manipulations of
      physicians affect hundreds of thousands of people. The defects of treatment are
      more obvious in surgery than in therapy. To qualify the manipulations of the
      therapist as proper or non-proper is much more difficult as compared with
      erroneous conclusion in diagnostics. Underestimation and belated resolution of
      this issue is fraught with the most grave consequences.

PMID- 17036456
TI  - [Cost availability and patient satisfaction of hospital care].
AB  - The results of sociological questionnaire of 1496 patients of oblast and region
      hospitals related to cost availability and patient satisfaction of hospital care.
      About 75% of respondents considered their treatment spendings as significant. It
      is established that degree of patients' satisfaction of hospital care depends on
      length of stay at the in-patient department. The longer it is the fewer patients
      satisfied with medical care are. It is proposed to organize in hospitals among
      socially unprotected patients evaluation of individual spendings for medical care
      to protect constitutional rights of the population and to reveal factual cost of
      medical care in the framework of the territorial program of public guarantees.

PMID- 17036457
TI  - [The analysis of morbidity of child population according municipal polyclinics
      data].

PMID- 17036458
TI  - [The quality of life of patients with oncological gynecological pathology during
      period of involution].
AB  - The representative group of women older than 40 years with oncological
      gynecological pathology during involution period was examined. Quality of life of
      these patients and their attitude to their health as well was studied during
      various rehabilitation periods of the course of this disease. Survey was applied
      using questionnaire MOS-SF 36 Health Survey 2.0 with subsequent statistical data
      processing. The results can be applied to enhance effectiveness of preventive
      activities in gynecology and practical and research medicine.

PMID- 17036459
TI  - [The study of the possibility of development and diagnostics of kidney diseases].

PMID- 17036460
TI  - [Diseases of musculo-skeletal system in railway personnel].
AB  - Epidemiological and medical-social aspects of diseases of locomotor system and
      conjunctive tissue in railway personnel (1993-2004) are analyzed. The established
      negative trends in propagation of diseases locomotor system predetermine priority
      of preventive measures in organization of medical care for the patients of this
      category. Establishment of medical rooms for preventing diseases of locomotor
      system is recommended.

PMID- 17036461
TI  - [The physical conditions of seventeen-year-old adolescents in Omskaya Oblast].
AB  - In Omskaya Oblast, among seventeen-year-old adolescents 70.5% of males and 58.5%
      of females are of sufficient degree of average, above average and higher physical
      state. Study of integrated impact of various factors on physical state deviations
      established that 33.9% of these factors belong to the medical category. This fact
      emphasizes higher significance of quality of applied diagnostic and therapeutic
      and preventive actions. Marked impact was also provided by living conditions
      (17.8%), education conditions (17.7%), family life-style (16.1%), natural
      climatic conditions and degree of anthropogenic pollution of environment (14.5%).
      Most of these factors are controllable enough to provide reserve for grading of
      lower degree of adolescents' physical state.

PMID- 17036462
TI  - [The medical personnel of hospice as object of study of professional activity
      impact on personality].
AB  - Data of questionnaire survey of clinical specialists providing medical care to
      oncological patients at IV stage of prevalent malignant neoplasms is discussed.
      Impact of professional activities on development of professional-personal
      desadaptation (burnout) in medical personnel is presented. Survey results permit
      to determine the approaches to psychological care and psychological monitoring of
      personnel activities in medical institutions of oncological services.

PMID- 17036464
TI  - [The system of dataware in quality management of medical care rendering in
      Samarskaya oblast].

PMID- 17036463
TI  - [The actual issues of ambulance medical care in the the Russian Federation].
AB  - Issues of organization of ambulance medical care to the population of the Russian
      Federation are discussed.

PMID- 17036465
TI  - [Marketing activities of sanatorium resort institutions].

PMID- 17036466
TI  - [The actual problems of organization of medical care for rural population].
AB  - Population health status and medical care in rural areas is discussed. Trends in
      dynamics of such health indicators as mortality, morbidity and prevalence of
      socially perilous diseases are worse among rural population as compared with
      urban population. Economical, environmental, industrial and other factors
      impacting on health of rural population are revealed. Sociological research data
      demonstrating attitude of rural population to health and to medical care are
      quoted. Problems of financing, manpower strength and material and technical
      equipping in rural health institutions are discussed. Importance of priority
      national project "Health" for enhancement of rural medical care is shown
      including necessary measures for its realization.

PMID- 17036467
TI  - [The role of special programs of HIV/AIDS prevention].

PMID- 17036468
TI  - [The characteristics of main resources of oncological institutions of Far East of
      the Russian Federation].

PMID- 17036469
TI  - [The conditions and ways enhancing stomatological care of rural population].

PMID- 17036470
TI  - [Dynamics and regional characteristics of medical demographic indicators in the
      Republic of Kazakstan].

PMID- 17036471
TI  - [The teaching of pathology in faculty of medicine of Moscow University in XVIII
      century].

PMID- 17036472
TI  - [The sanitary organization of cities of Russia in the late XIX--early XX
      centuries].

PMID- 17036473
TI  - [From the history of Zemstvo pharmacy (according materials from Kurskaya
      province)].

PMID- 17036474
TI  - [Clinical observation on catgut implantation at acupoint for treatment of general
      paroxysmal epilepsy].
AB  - OBJECTIVE: To search for an effective method for treatment of general paroxysmal
      epilepsy. METHODS: One hundred cases were randomly divided into a treatment group
      of 50 cases treated with catgut implantation at Dazhui (GV 14), Jinsuo (GV 8),
      Fenglong (ST 40), etc., and a control group of 50 cases treated with oral
      administration of sodium valproate. RESULTS: The scores for epilepsy after
      treatment significantly improved in the both groups (P<0.05); the total effective
      rate was 94.0% in the treatment group and 82.0% in the control group with a
      significant difference between the two groups (P<0.05). CONCLUSION: Catgut
      implantation at acupoint has a definite therapeutic effect on general paroxysmal
      epilepsy with no adverse effect.

PMID- 17036475
TI  - [Observation on treatment of chronic pelvic inflammatory with point injection
      combined with ultra-laser radiation].
AB  - OBJECTIVE: To probe into clinical therapeutic effect of point injection combined
      with ultra-laser radiation on chronic pelvic inflammatory. METHODS: Sixty cases
      of chronic pelvic inflammatory were divided into a treatment group and a control
      group, 30 cases in each group. The treatment group were treated with point
      injection of Yuxingcao Injectio combined with ultra-laser point radiation, and
      the control group with simple point injection of Yuxingcao Injectio, once each
      day, for 4 weeks. RESULTS: Twenty-eight cases were effective with a total
      effective rate of 93.3% in the treatment group, and 23 cases were effective with
      a total effective rate of 76.7%; the weighty pain of lower abdomen, abnormal
      leucorrhea and signs of gynecological examination, etc. in the treatment group
      significantly improved as compared with the control group (P<0.05). CONCLUSION:
      Point injection combined with ultra-laser radiation has definite therapeutic
      effect on chronic pelvic inflammatory.

PMID- 17036476
TI  - [Clinical observation on therapeutic effect of electroacupuncture at Sanyinjiao
      (SP 6) on peri-menopausal syndrome].
AB  - OBJECTIVE: To objectively evaluate the effectiveness and safety of
      electroacupuncture (EA) at Sanyinjiao (SP 6) for treatment of peri-menopausal
      syndrome. METHODS: All the patients enrolled were randomly divided into a
      treatment group and a control group. The treatment group were treated with EA at
      Sanyinjiao (SP 6) for 3 therapeutic courses, thrice each week, 30 min each time,
      one month constituting one course. The control group were treated with oral
      administration of nylestriol for 3 months, 2 mg each time, twice each month. For
      the menopausal patient, medroxyprogesterone was added from the third month of the
      treatment for 7 days, 6 mg each day. Changes of vasomotorial symptoms, mental
      symptoms and scores of Kupperman indexes before and after treatment for 1 month,
      2 months and 3 months were investigated. RESULTS: EA could significantly decrease
      the score of Kupperman indexes, improve vasomotorial symptoms and mental symptoms
      in the patient of peri-menopausal syndrome with no severe adverse effects. The
      control group in the score of Kupperman indexes was slightly higher than the
      treatment group with no significant difference between the two groups, but the
      treatment group in improvement of the vasomotorial symptoms was better than the
      control group and in improvement of mental symptoms was not as good as the
      control group. CONCLUSION: EA at Sanyinjiao (SP 6) is effective and safe for
      treatment of peri-menopausal syndrome.

PMID- 17036477
TI  - [Randomized controlled study on ginger-salt-partitioned moxibustion at shenque
      (CV 8) on urination disorders poststroke].
AB  - OBJECTIVE: To probe the therapeutic effect and safety of ginger-salt-partitioned
      moxibustion on urination disorders poststroke. METHODS: Eighty-two cases of
      cerebral apoplexy, including cerebral infarction and cerebral hemorrhage, with
      urination disorders induced by neurogenic bladder at restoration stage were
      randomly divided into a treatment group treated with ginger-salt-partitioned
      moxibustion at Shenque (CV 8) and routine acupuncture, and a control group
      treated with routine acupuncture. Thirty-nine cases in the treatment group and 36
      cases in the control group completed all treatments. The treatment was given 5
      times each week and the therapeutic effects were observed after treatment of 3
      consecutive weeks. RESULTS: Ginger-salt-partitioned moxibustion in improvement of
      mean urination times of each day, mean times to be asked to awaken for the
      nursing personnel at night, mean times of urgent urinary incontinence at day for
      the patient, cases-times of urinary incontinence of the patient at night, and
      increasing degree of urinary incontinence was better than the control group
      (P<0.01, P<0.05). CONCLUSION: Ginger-salt-partitioned moxibustion is a safe and
      effective therapy for urination disorders poststroke.

PMID- 17036479
TI  - [Clinical observation on acupuncture for treatment of central obesity].
AB  - OBJECTIVE: To observe and evaluate objective therapeutic effect of acupuncture on
      central obesity. METHODS: Thirty-two cases of central obesity were treated with
      body acupuncture combined with electroacupuncture, ear point tapping, TDP
      radiation, and changes of WC, WHR and body mass index (BMI) before and after
      treatment were observed. RESULTS: The clinical total effective rate was 84.4%,
      and WC, WHR and BMI decreased (P<0.001). CONCLUSION: Acupuncture combined with
      electroacupuncture, ear point tapping, TDP radiation has a better therapeutic
      effect on central obesity.

PMID- 17036478
TI  - [Effects of injection of Huangqi injectio into Zusanli (ST 36) on immune function
      in the patient of schizophrenia].
AB  - OBJECTIVE: To study on effects of injection of Huangqi Injectio into Zusanli (ST
      36) on the hospital infection and immune function in the patient of
      schizophrenia. METHODS: Thirty inpatients of chronic schizophrenia were treated
      with injection of Huangqi Injectio into bilateral Zusanli (ST 36), 2 mL each
      point, thrice each week, for 8 weeks. Relative immune indexes and the hospital
      infection were investigated. RESULTS: The hospital infection and the sub
      infection were 4 cases (13.3%), 7 cases-times (23.3%) in the injection group; and
      9 cases (15.0%), 19 cases-times (31.7%) in the control group, respectively, with
      no significant difference between the two groups (P>0.05). The drug
      administration duration was 7.77 days/case and 11.87 days/case in the two groups,
      respectively (P<0.01). In the injection group, as compared with that of last 3
      years the duration was 7.77 days/case and 14.08 days/case (P<0.01). IgG, IgA, IgM
      and T-cell subgroups did not have significant changes, but there was the most
      different value before and after injection in SIL-2R of the no-infection group,
      and the longer the drug administration duration, the smaller the different
      values. CONCLUSION: Injection of Huangqi Injectio into Zusanli (ST 36) has
      definite effect for prevention of the hospital infection in inpatients of chronic
      schizophrenia, and SIL-2R is a valuable index for investigation of the hospital
      of infection.

PMID- 17036480
TI  - [Application of acupuncture in imaging of changing pyloric antrum and duodenal
      bulb metamorphosis].
AB  - OBJECTIVE: To probe into the effect of acupuncture in imaging diagnosis on
      changing pyloric antrum and duodenal bulb metamorphosis, and provide reliable
      evidence for confirming pathological characters. METHODS: Among 30 cases needing
      image examination, 18 cases had metamorphosis of duodenal bulb and 12 cases had
      metamorphosis of pyloric antrum. Acupuncture was given at Zusanli (ST 36) with
      uniform reinforcing-reducing method, and with moderate-strong stimulation. The
      needle was retained for 2 min. After pressing point Zhongwan (CV 12), changes of
      image were investigated. RESULTS: After acupuncture, the metamorphosis alleviated
      in 26 cases, with an effective rate of 86.7%. CONCLUSION: This method is simple,
      convenient and objective with no adverse effects.

PMID- 17036481
TI  - [Study on the needling depth of point Yaotu with CT scanning].
AB  - OBJECTIVE: To probe the safe depth and angle of needling the point Yaotu for
      treatment of prolapse of intervertebral disc. METHODS: CT technique was used for
      scanning investigation of the depth and angle of needling the point Yaotu.
      RESULTS: When the acupuncture needle was inserted vertically to the external
      space of intervertebral foramen of human body with arrival of qi, the tip of
      needle could reach to 73 mm deep, which is the best needling depth and angle.
      CONCLUSION: The needle vertically inserting to the external space of
      intervertebral foramen at the point Yaotu is proper in treatment of prolapse of
      intervertebral disc.

PMID- 17036482
TI  - [Re-cognition of the Jinglin theory in the Internal Classic].
AB  - OBJECTIVE: To summarize the Jijgiin theory and study the essence of Jingjin.
      METHODS: Analyze the meaning of the word, anatomical basis, symptoms and
      treatment of Jingjin. CONCLUSION: The Jingjin theory in the Internal Classic is
      formed on the basis of 12 division method of the surface, reflecting internal
      relations among the skeletal muscles and the crux of injury, and summarizing
      treatment methods of Jingjin diseases; and the meaning of essence of the Jingjin
      is nerve and muscles.

PMID- 17036483
TI  - [Study on vascular morphology of integument tissues of the channel area in the
      leg].
AB  - OBJECTIVE: To observe the distribution of the blood vessels in the integument
      tissue of the channel area of legs. METHODS: The integument tissue of the lower
      limbs in the 12 cadavers were dissected with macro-and micro-dissection,
      radiographical technique of systemic artery and technique of image pattern
      analysis to observe and analyze the origins, branches and anastomoses in the
      integument tissues along the channels of legs. RESULTS: The distributional
      density of the blood vessels in the integument tissues of legs along the channel
      area of the three-yin meridians of the foot, the Gallbladder Meridian, and the
      Urinary Bladder Meridian was higher than that in the other parts. They formed an
      obvious nutrient vascular chain on the arteriogram. The distributional density in
      the channel area of the Stomach Meridian was not obviously increased and the
      obvious nutrient vascular chain could not be seen. CONCLUSION: An obvious
      nutrient vascular chain is formed in the integument tissue along the channel area
      of legs except the Stomach Meridian.

PMID- 17036484
TI  - [Effects of different acupuncture intensities on the therapeutic effect and the
      gastric electric activity in the patient of diabetic gastroparesis].
AB  - OBJECTIVE: To observe clinical therapeutic effect of different acupuncture
      intensities on diabetic gastroparesis and to search for the best acupuncture
      intensity for treatment of diabetic gastroparesis. METHODS: Eighty cases were
      randomly divided into 4 groups, strong, moderate, weak acupuncture intensity
      groups and an oral hypoglycemic drug group, 20 cases in each group. Two weeks of
      treatment constituted one course. RESULTS: The total effective rates were 85.0%,
      95.0%, 85.0% in the acupuncture groups, respectivelly, with significant
      difference as compared with 65.0% of the control group (P<0.05). The moderate
      intensity acupuncture group had the best clinical therapeutic effect. The
      principal frequency and amplitude of the stomach electrogastrogram in the gastric
      antrum and the stomach body significantly improved in the acupuncture groups,
      which was better than those in the control group (P<0.05). CONCLUSION:
      Acupuncture has significant therapeutic effect on diabetic gastroparesis, and
      there is a dose-effect relation between different intensities of acupuncture and
      curative effects,which are correlated with the regulation of the gastric electric
      parameters.

PMID- 17036485
TI  - [Comparison of therapeutic effects between normal acupuncture and shallow
      needling with short-needle on periarthritis of shoulder].
AB  - OBJECTIVE: To compare therapeutic effects between normal acupuncture and shallow
      needling with short-needle, and search for therapeutic tool and method easy to be
      accepted by the patient of periarthritis of shoulder. METHODS: One hundred and
      fifty-two cases of periarthritis of shoulder were randomly divided into 2 groups.
      They were treated by normal acupuncture and shallow needling with short-needle,
      respectively. The two groups were same in acupoints selected and the therapeutic
      course, and their therapeutic effects and the accepting degrees of the patient
      were investigated. RESULTS: The cured rate was 67.1% in the normal acupuncture
      group and 69.7% in the shallow needling with short-needle group, with no
      significant difference between the two groups (P>0.05). CONCLUSION: Normal
      acupuncture and shallow needling with short-needle have similar therapeutic
      effect on periarthritis of shoulder, but the shallow needling with short-needle
      can obviously relieve the pain and mental fear in treatment, easy to be accepted.

PMID- 17036486
TI  - [Effects of acupuncture on expressions of transcription factors NF-E2, YB-1,
      LRG47 in the SAMP10 mouse].
AB  - OBJECTIVE: To explore the mechanism of acupuncture in delaying aging. METHODS:
      Using SAMP10 mice and normal control SAMR1 as model and applying RT-PCR and DIG
      probed Northern blot techniques to observe expression of NF-E2, YB-1, LRG47 genes
      in whole brain, cortex and hippocampus in the 8-month SAMR1 control group, 8
      month SAMP10 control group, 8-month SAMP10 acupuncture group and 8-month SAMP10
      non-point acupuncture group. RESULTS: In the SAMP10 control group, the expression
      of NF-E2, YB-1 and LRG47 were down-regulated in the whole brain, cortex and
      hippocampus, and after acupuncture they were up-regulated and tended to normal.
      CONCLUSION: Aging of the SAMP10 mouse brain is related with expression of NF-E2,
      YB-1 and LRG47 genes, and acupuncture can regulate the expression of NF-E2, YB-1
      and LRG47 genes, improving the functions of erythrocyte series, increasing
      proliferation of cells and immune function of cells in anti-bacteria, hence anti
      aging.

PMID- 17036487
TI  - [Effects of electroacupuncture on behaviors and dopaminergic neurons in the rat
      of Parkinson's disease].
AB  - OBJECTIVE: To explore the possibility of electroacupuncture (EA) for prevention
      of the injury of dopaminergic neurons in the substantia nigra of the rat with
      Parkinson's disease. METHODS: Wistar rats were randomly divided into a normal
      group, a model group, a sham-operation group and an EA group. 6-OH-DA was
      injected into right substantia nigra of the midbrain to made Parkinson's disease
      rat model with single side substantia nigra injury, and TH/TUNEL method and
      rotation behavior observation method were used to observe changes of rotation
      behavior and apoptosis of dopaminergic neurons in the substantia nigra after EA
      at "Taichong" (LR 3) and "Fengfu" (GV 16) for 3 d, 7 d and 14 d. RESULTS: The
      rotation times/min were same at 3 d, 7 d and 14 d were the basically same in the
      model group, and at 14 d significantly decreased in the EA group (P<0.05); the
      rotation starting time at 7 d and 14 d in the model group were significantly
      longer than those in the EA group (P<0.05); the rotation lasting time at 3 d, 7 d
      and 14 d in the model group and the EA group were gradually shortened (P<0.01, or
      P<0.05), but at 7 d, 14 d in the model group were significantly longer than those
      in the EA group (P<0.05); the DA neuron apoptosis number in the model group were
      significantly higher than those in the normal group, with a very significant
      difference (P<0.01); the apoptosis number in the EA group tended to decrease, at
      7 d and 14 d were significantly lower than that in the model group (P<0.05).
      CONCLUSION: Electroacupuncture can effectively prevent from injury of
      dopaminergic neurons in the substantia nigra of the rat with Parkinson's disease.

PMID- 17036488
TI  - [Observation on therapeutic effect of scalp acupuncture analgesia on labor].
AB  - OBJECTIVE: To observe analgesic effect of scalp acupuncture on labor. METHODS:
      Seventy primiparae with term pregnancy and monocyesis were randomly divided into
      scalp acupuncture group treated by acupuncture at the Shengzhi area of scalp, and
      control group by no treatment. Pain grades before and after scalp acupuncture
      were evaluated with the pain 4-grade rating criteria stipulated by WHO, and the
      active stage and the second birth process, the Apgar scores of new-born and
      postpartum hemorrage amount were compared between the two groups. RESULTS: The
      labor pain with 1 to approximately 2 grades was found in 33 cases in the scalp
      acupuncture group, and 2 cases in the control group with very significant
      difference between the two groups (P < 0.01); the active stage was (130.70 +/-
      74.16 ) min and the second birth process was (40.70 +/- 21.65) min in the scalp
      acupuncture group, and (166.15 +/- 62.65) min and (53.30 +/- 26.93) min in the
      control group, respectively, with significant differences between the two groups
      (all P < 0.05); and there were no significant differences in Apgar score of new
      born and postpartum hemorrhage amount. CONCLUSION: Scalp acupuncture has a better
      analgesic effect in vaginal delivery with no adverse effect on the mother and
      infant.

PMID- 17036489
TI  - [Prof. WU Lian-zhong's 12 acupuncture analgesic methods].
AB  - Prof. WU Lian-zhong not only has great theoretical attainments and rich clinical
      experience, but also is good at summarization and study, especially,
      systematically and deep study on various kinds of pain from etiology,
      pathogenesis, characteristics, classification and syndrome differentiation,
      treatment method and point selection and other aspects, and sums up the 12
      treatment methods such as regulating mental activities, removing obstruction in
      the channels, opposing needling, blood-letting puncture, sixteen cleft points,
      warming the channels, resistant needling, Su needling, surrounding needling,
      tripod needling, penetration needling and dragon-tiger contending method, which
      are of very important significance for guiding clinical acupuncture analgesia.

PMID- 17036490
TI  - [Brief discusion on importance of accurate location in acupuncture treatment for
      periarthritis of shoulder].
AB  - Briefly discuss some recognation problems about acupuncture treatment of
      periarthritis of shoulder at present and put forward the methods for diagnosis
      and acupuncture treatment based on accurate location.

PMID- 17036491
TI  - [A new thinking of acupuncture and moxibustion treatment of shoulder pain after
      hemiplegia].
AB  - Analysis from anatomy and physiology indicates that causes of shoulder pain are
      (1) decline and after-constriction of the scapula;(2) the adduction and intorsion
      of the humerus; (3) the spasm of the upper limb flexor. The acupuncture and
      moxibustion prescriptions stipulated for prevention and treatment of shoulder
      pain are Jianjing (GB 21), Jianzhongshu (SI 15), Jugu (LI 16), Tianzong (SI 11),
      Jianliao (SJ 14), Jiquan (HT 1) at the flaccid hemiplegia, and Jugu (LI 16),
      Jianyu (LI 15), Tianzong (SI 11), Jianliao (SJ 14), Xiaoluo (SJ 12), Shanglian
      (LI 9), Wenliu (LI 7) at the spastic hemiplegia , in combination with cupping at
      the Urinary Bladder Meridian on the back and around shoulder. Thus, it is
      indicated that shoulder pain not only is involved in the shoulder joint but also
      in all muscle groups of the shoulder girdle and the upper limb extensor at the
      affected side.

PMID- 17036492
TI  - [Exploration and reflection on bilingual teaching of acupuncture and
      moxibustion].
AB  - OBJECTIVE: To explore bilingual teaching of acupuncture and moxibustion for
      cultivating compound senior acupuncture persons. METHODS: Beginning with the
      concept of bilingual teaching in conjunction with acupuncture own
      characteristics, the problems involved in the practice of bilingual teaching of
      acupuncture and moxibustion were analyzed and explored. RESULTS: Unifying opinion
      and correct localizing position should be started for acupuncture and moxibustion
      bilingual teaching, and choice of teachers, subjects, models, materials,
      examination of bilingual teaching should be focused on, and appropriate means
      should be applied in practice to test, consolidate and distillate the effect of
      bilingual teaching. CONCLUSION: Bilingual teaching of acupuncture and moxibustion
      is an important measure of economic globalization and knowledge economy. Only if
      various teaches involved in its practice were properly dealt with could better
      teaching results be obtained.

PMID- 17036493
TI  - [Jingluo, Jingmai and their English translation].
AB  - Chinese meaning and English translation of Jing, Luo, Mai, Jingluo, Jingmai and
      other terminology of Chinese medicine are compared from both writing and medical
      theory, raising that the Jingmai in the Internal Classic should include both the
      channel system and the vessel system. From the form of the characters or
      functions and structures, the Jing is longitude and the Luo is net, Mai is
      vessels, and the concept and function of Jingluo (channels and collaterals) and
      Jingmai (the meridians and vessels) do not allow obscure. In ancient times, Jing
      and Mai were jointly called as Jingmai, aimed at understanding network state of
      the channels and collateral system through tangible distribution of the vesselar
      system. Translation of "Jing mai" as the meridians and collaterals or channels
      and collaterals practically is only translated a half of real meaning of Jingmai.

PMID- 17036494
TI  - [Survey of point prescriptions of acupuncture treatment for urinary retention].
AB  - OBJECTIVE: To summarize characteristics of the point prescriptions for
      acupuncture treatment of urinary retention from 1994 to 2005. METHODS: Review of
      literature was made from following five aspects: body acupuncture, scalp
      acupuncture, ear acupuncture, hand acupuncture and abdomen acupuncture. For the
      prescriptions of body acupuncture, further analysis was made on single point
      prescription, distal-proximal point association, superior-inferior point
      association, point selection according to syndrome differentiation and point
      selection according to disease differentiation. CONCLUSION: Acupuncture has
      affirmative therapeutic effect on urinary retention. However, there are still
      problems to be resolved in clinical researches at present.

PMID- 17036495
TI  - [On key role of acupoints in elongated needle therapy].
AB  - OBJECTIVE: To study on characteristics and application of key acupoints in
      Elongated Needle Therapy. METHODS: Probe into method of determining key acupoints
      and their clinical application from characteristics of channels, characteristics
      of acupoints, position of diseases, pathogenesis, syndromes and other aspects.
      CONCLUSION: Establishment of the theory of key acupoints of enlongated needle
      therapy reflects the principle of "fewer but better" in acupoint selection of
      enlongated needle therapy, which can reduce pain of the patient and increase the
      therapeutic

PMID- 17036496
TI  - [The role of inflammation in the pathogenesis of late diabetic complications].
AB  - Chronic inflammation plays an important role in the development of diabetes and
      its late complications. Over nutrition, physical inactivity, stress, truncal
      obesity, dyslipidaemia, hypertension and smoking directly and indirectly activate
      the family of nuclear factor kappa B, the principal factor of inflammatory
      response. Hiperglycaemia and especially brittle diabetes affect not only
      metabolic abnormalities but also modulate cell and humoral immune response. There
      is good evidence that looking for novel risk factors for development and
      progression of late diabetic complications among inflammatory markers are needed.
      Progress in the study on etiopathogenesis of micro- and macro-angiopathy have
      clinical implications.

PMID- 17036497
TI  - [Implantation of cardiac pacemaker in children, author's experiences].
AB  - Cardiac pacemaker was implanted as a therapeutic method for children with atrio
      ventricular block, sick sinus syndrome, LQT syndrome, cardio-depressive syncope.
      Twenty six children (aged 1-17) underwent pacemaker implantation or exchange of
      pacemaker and electrode. In nineteen cases cardiac peacemaker was implanted in
      the endocardial system; in the next seven cases epicardial system was required.
      The difference between the implantations depended on patient's age and the
      character of the disease. The single chamber peacemaker was implanted in twenty
      children, dual-chamber in six patients. There were no visible complications in
      follow up observation and constant heart stimulation can be considered as a safe
      way of children's severe bradycardia treatment.

PMID- 17036498
TI  - [Serum cytokine concentration as prognostic factor in patients with alcoholic
      liver disease].
AB  - AIM OF THE STUDY: Estimation if the serum concentration of cytokines: IL-2, IL-4,
      IL-6, IL-8, IL-10, TNF-alfa and CRP can be useful in the assessment of prognosis
      in patients with alcoholic hepatitis (ALH) and alcoholic liver cirrhosis (ALC).
      Attempt to find their correlation with clinical stage and life prognosis in all
      patients. MATERIALS AND METHODS: We examined 24 patients with alcoholic liver
      disease, hospitalised in Department of Gastroenterology: 13 male and 11 female at
      the age 26-72 years. According to clinical symptoms and laboratory tests in 15 of
      them alcoholic hepatitis (in 9 confirmed by liver biopsy) and in 9 - liver
      cirrhosis (2 confirmed by liver biopsy) were diagnosed. The interview, physical
      examination, abdominal ultrasound, biochemical tests and viral tests were
      performed in all patients. We excluded patients treated with steroids and
      cytostatics. Serum concentration of cytokines and CRP were established three
      times during the first week of hospitalisation. RESULTS AND CONCLUSIONS: In all
      patients IL-2 and IL-4 concentration were in a range characteristic for healthy
      people. There was statistically important correlation between the severe clinical
      stage and high concentration of serum IL-6 (p<0.000319), IL-8 (p<0.000708), TNF
      alfa (p<0.000018) and CRP (p< 0.001611) in patients with ALC. High concentration
      of serum IL-6, IL-8, TNF-alfa and CRP were correlated with poor prognosis (3
      patients with ALC and the highest concentration died). High concentration of IL
      6, IL-8, TNF-alfa and CRP were correlated with heavy clinical stage and poor
      prognosis so their evaluation can be helpful in the assessment of prognosis in
      patients with ALC and ALH.

PMID- 17036499
TI  - [Clinical image of oral mucous membrane in rheumatoid arthritis patients].
AB  - The aim of the study was to evaluate the character and frequency of pathological
      changes in the oral cavity mucous membrane and xerostomy in patients with
      prolonged hospital and ambulatory treatment due to rheumatoid arthritis (RA).
      EXAMINATION MATERIAL: The study was conducted in 120 patients with RA, average
      age 54, and in the control group of 40 generally healthy examinees, average age
      53. RESULTS: In patients with RA pathological changes in the oral cavity appeared
      much more frequently: erosions, fissures, perleche, candidiasis oris, lichen
      Wilsoni, leukoplakia and persistent xerostomy. RA patients more often used
      partial prosthesis and more frequently were edentulous. CONCLUSIONS: The
      treatment of oral cavity diseases and prophylaxis should be provided together
      with the RA treatment, with special emphasis put on the elimination of xerostomy.
      Good cooperation of rheumatologists and periodontologists is recommended RA
      diagnosis.

PMID- 17036500
TI  - [Candida infections of the oral mucosa--not only a dental problem].
AB  - Frequency of occurrence of mycotic infections of the oral mucosa is higher in
      later years. It is connected with common use of antibiotics, intensive cancer
      treatment (cytostatics, radiation therapy) as well as immunosuppressant drugs and
      antibiotics, which have an influence on mikroflora disorders of the oral cavity.
      Candidiasis of oral mucosa occurs in old patients, in people suffering from
      diabetes mellitus, hypothyreosis, sideropenia, hypovitaminosis and xerostomia,
      which is often caused by hypofunction of salivary glands during autoimmune
      diseases and/or drug and systemic treatment. The aim of the study was to make a
      retrospective evaluation of frequency of occurring mycotic infections in patients
      treated in the Department of Periodontology and Oral Mucosa Diseases, Medical
      University of Gdansk in the 2003, as well as recognition of systemic conditioning
      of these disorders. The Study material was clinical documentation of 4172
      patients, treated because of different oral mucose and periodontium disorders.
      From these patients, selected was a group of 105 (83 women and 22 men) with
      diagnosis--Candidosis mucosae oris. Clinical and mycotic examination was
      performed. RESULTS: Mycotic infections were found in 105 patients (2.5%).
      Systemic diseases (74.3%) were found in a maturity of the patients, which
      indicated systemic predispositions to candida infections. CONCLUSION: A wide
      cooperation between general practitioners and dentists, especially perio
      dontologists, is necessary to give full care to patients. Early diagnosis of
      disorders of the oral cavity of patients with systemic diseases and dentistry
      treatment or taking preventive measures seems to be necessary.

PMID- 17036501
TI  - [Completed suicide in outline--on basis of Cracow's Institute of Forensic
      Medicine data in 1991-2000 years].
AB  - The study presents the results of research into completed suicide. The authors
      have analyzed cases of completed suicide committed in Cracow and it's environs in
      the years 1991-2000. The aim of the research is to describe some features of this
      phenomenon with it's transformations in the last periods. The presented material
      bases on archival data of postmortem examinations made in Cracow's Institute of
      Forensic Medicine. Analyses' were executed in reference of victims' sex, age and
      place of residence, number and frequency of suicides in Cracow population,
      methods, predictors and possible motives. The authors also present a sketch of
      the bibliography regarding the topic, and the comparison between the results of
      the present study and the results of earlier studies from Cracow environs of the
      phenomenon of suicide. 1933 cases of completed suicides were analysed, from what
      over a half concerned occupants of our city. The average coefficient for 100 000
      occupants carried out 13.2. There were 1485 men and 448 women among victims, in
      age from 13 to 95 years. Male to female avarage ratio carried out 3.3:1 in the
      described period.. Average age carried out 45.5 years, for men 44.5, and for
      women 48.8 years. The superiority of men is strongly visible in groups of young
      persons and in "middle age". Results from archival data show that, hanging was
      the the most frequent way of suicide. In studied material there were more then
      63% cases of suicidal hanging. Falls from height, poisonings and drownings were
      next in line. In very considerable number of cases (almost 60%) the presence of
      mental disorder in anamnesis was affirmed. This concerned particularly women
      where the most frequent were depression disorders. For men, first of all factors
      was dependence from acohol. Over one third of the victims were pensioners and
      unemployeds. The level of ethanol in blood in 718 cases was crossed 0.5 promille.

PMID- 17036502
TI  - [Concentration and activity of cathepsin D in the blood plasma and serum of
      patients with abdominal aortic aneurysm].
AB  - Concentration and activity of cathepsin D are markedly higher in the blood plasma
      of patients with abdominal aortic aneurysm than in the blood plasma of healthy
      subjects. The difference results from release of big amounts of procathepsin D
      and increased release of the active enzyme into circulating blood of patients
      with aortic aneurysm. Concentration and activity of cathepsin D in the blood
      serum of patients with aortic aneurysm are also higher than in the serum of
      healthy subjects. Concentration and activity of cathepsin D are markedly higher
      in the blood serum of patients with aortic aneurysm and in healthy subjects as
      compared to the blood plasma. The difference is due to the release of marked
      amounts of procathepsin D and cathepsin D from morphotic elements in vitro during
      blood coagulation and clot retraction.

PMID- 17036503
TI  - [Incidence, pathogenesis and importance of nocturnal hypoxaemia in patients with
      chronic obstructive pulmonary disease].
AB  - Noctural hypoxaemia (NH) in patients with chronic obstructive pulmonary disease
      (COPD) was first described over 40 years ago, however, its importance is not
      fully established. NH is defined most frequently as a drop in oxygen saturation
      below 90% and it occurs in almost all COPD patients PaO2 < 55 mmHg and in 30-40%
      of those with PaO2 < 60 mmHg. The main reason for NH is alveolar hypoventilation
      which is most pronounced during ohase REM. It is known that even short term
      episodes of NH increase pulmonary artery pressure, yet, the impact of chronic,
      isolated NH on pulmonary hypertension development was not found. Also, the
      relationship of induced by NH cardiac arrythmias with sudden death in COPD was
      not documented and association of NH with prognosis in COPD was not proved.
      Actually, there is no need to perform NH examination routinely. According to the
      ATS/ERS latest standards, the determination of NH can be helpful to qualify COPD
      patients with PaO2 55-65 mmHg to longterm oxygen therapy.

PMID- 17036504
TI  - [Clinical implication of ischemic preconditioning in protection of reperfused
      tissues].
AB  - Ischemic preconditioning (IP), has emerged as a powerful experimental method of
      ameliorating ischemic-reperfusion injury in a variety of organs. Clinical trials
      using IP have been successfully carried out. They support the existence of IP
      induced cyto-protection in humans as well. IP induced "ischemia tolerance" and
      "reperfusion tolerance" mechanisms are presented. The new, recently discovered
      modifications of IP "remote preconditioning" and "postconditioning" and their
      possible clinical applications in the ischemia of human: heart, liver, lung,
      brain, kidney and skeletal muscles are discussed.

PMID- 17036505
TI  - [Difficulties in differential diagnosis of Sjogren's syndrome and systemic lupus
      erythematosus].
AB  - Sjogren's Syndrome (SS) is the second most common autoimmune disorder after
      rheumatoid arthritis (RA). It can be found as a lone condition (primary Sjogren's
      Syndrome) or may accompany other autoimmune rheumatic diseases (secondary
      Sjogren's Syndrome). Despite such frequent occurrence, accurate diagnosis of
      Sjogren Syndrome is difficult. These difficulties result from highly variable
      symptoms of SS as well as from common presence of other autoimmune disorders. In
      the following article authors present current knowledge concerning clinical
      symptoms, diagnostic methods and latest clinical guidelines on the diagnosis of
      SS. Differential diagnosis of SS and systemic lupus erythematosus (SLE) is also
      discussed.

PMID- 17036506
TI  - [The evolution of insulin therapy and new insight into nutrition recommendations
      for individuals with diabetes].
AB  - The dietary guideline has undergone change during the last decades. It has been
      done by the introduction of new insulin therapy methods, also by the numerous
      epidemiological studies which have documented the influence of eating habits on
      macro-vascular diseases, obesity and type 2 diabetes. The Glycemic Index (GI) and
      Glycemic Load (GL) play a pivotal role in carbohydrate classification and for
      food choice by diabetic patients. Post-prandial glycemia response and insulinemia
      strongly relate to value of GI and GL. Intensive insulin therapy as a multiple
      daily injection or pump therapy has brought a liberalization in diabetic regime
      and diet. It gives possibility to introduce modern dietary guidelines including
      healthy eating advice with respect for traditional eating habits.

PMID- 17036507
TI  - [The role of glycemic index concept in carbohydrate metabolism].
AB  - Glycemic index (GI) is a system of classifying carbohydrate-containing foods
      according to how fast they are digested and absorbed during the postprandial
      period. It is a measure of the quality of carbohydrates based on their direct
      effect on blood glucose levels during 2 hours after the meal. As a reference
      point--glucose is used, with GI equal 100. A related concept, glycemic load (GL),
      take into consideration also amount of carbohydrates in portion of food. GL is
      calculated by multiplying the GI by the amount of available carbohydrates (g) and
      dividing total by 100. GI's value can be affected by a number of factors,
      including the variety and ripeness of food or method of processing, cooking and
      storage. GI of particular product, as well as mixed meal is modulated by other
      food components like fat, protein, organic acids, dietary fiber and also
      antynutrients. In general, low GI foods include most fruits and vegetables, beans
      and legumes, and whole grain products. Refined grain products and potatoes have a
      high GI. The GI has proven to be a more useful nutritional tool than is the
      traditional classification of carbohydrates (as simple or complex, as sugars or
      starches, or as available or unavailable), permitting new insights into the
      relation between the physiologic effects of carbohydrate-rich foods and health.
      Several prospective observational studies have shown that the chronic consumption
      of a diet with a high glycemic load is independently associated with an increased
      risk of obesity, developing type 2 diabetes, cardiovascular disease, and certain
      cancers.

PMID- 17036508
TI  - [Education of the patient for therapy with personal insulin pump].
AB  - Insulin pump therapy is a diabetes management tool that can significantly aid in
      achieving treatment goals in children, adolescents and adults with type 1
      diabetes mellitus. These goals include optimal glycaemic control, lifestyle
      flexibility, quality-of-life improvement, and independence. Successful
      implementation of CSII requires a motivated, conscientious patient with a range
      of technical skills and self-management capabilities. Patients develop this
      knowledge through the program of education provided by a healthcare team
      including diabetologists, diabetes educator, dietietian, pump manufacturer
      representative, and in some cases, mental health professionals. Training of the
      patient to use a pump includes three basic steps: 1 - pre-pump education, 2 -
      pump start-up, 3 - evaluation, independence assessment and re-education. It is a
      relatively long process that can range from a few weeks to several months.
      Insulin pump therapy checklist, included in this paper, is a useful tool in
      planning and providing education for insulin pump users.

PMID- 17036509
TI  - [The role of transforming growth factor-beta in the pathogenesis of diabetic
      retinopathy].
AB  - Diabetic retinopathy is a micro-angiopathy affecting predominantly small vessels
      of the retina. Proliferative diabetic retinopathy is characterised by preretinal
      neovascularisation and fibrosis leading to vitreous heamorrhage and tractional
      retinal detachment. Chronic hyperglicemia may cause growth factor alterations
      that are likely to participate in tissue remodeling typical for this late
      complication. Numerous angiogenic and mitogenic factors have been demonstrated to
      be present in the eye, including transforming growth factor-beta (TGF-beta),
      insulin-like growth factors, fibroblast growth factor, tumor necrosis factor and
      vascular endothelial growth factor. TGF-beta is involved in the control of
      endothelial cell proliferation, adhesion and deposition of extracellular matrix,
      thus TGF-beta may play a role in the control of endothelial cell proliferation
      seen in the disease. The role of TGF-beta in diabetic retinopathy enables better
      understanding, and thus in the future better intensive antidiabetic therapy in
      aspect of ophthalmic complications.

PMID- 17036510
TI  - [Procedures in treatment of hemorrhoids].
AB  - Current conceptsof ethiopathogenesis and classification of hemorrhoids are
      presented based on the literature and own experience of the authors. Different
      surgical and non-surgical methods are discussed with additional description of
      postoperative treatment and complications.

PMID- 17036511
TI  - [Recurrent crural phlegmonous abscesses as a sign of Munchausen syndrome in a
      young woman].
AB  - We present a case of a 22-year-old woman chronically treated in many hospitals
      because of recurrent crural phlegmonous abscesses. Several months' follow up
      revealed Munchausen syndrome--a rare psychiatric disorder--manifesting with self
      perpetuated and repeated fabrication of illness resulting in wandering from
      hospital to hospital for diagnosis and treatment. The above patient produced the
      abscesses by deliberately traumatizing her skin. The case points to Munchausen
      syndrome as a possible rare cause of some long, unsuccessfully treated diseases.

PMID- 17036512
TI  - [Giant hydronephrosis of the upper left kidney in the case of complete, one-sided
      double pelvis].
AB  - We present the case of giant hydronephrosis in double pelvis of the left kidney.
      Patient was admitted to the urology department with hypertension and palpable
      giant mass in the abdomen. During imaging examination (CT, MRI ) the diagnosis of
      double pelvis and ureter on left side was established. The upper collecting
      system was extremely hydronephrotic and afunctional. Patient underwent partial
      nephrectomy - upper part of left kidney. We evacuated 9 liters of stagnated
      urine. After surgery blood pressure normalised, renal efficiency remained normal.

PMID- 17036513
TI  - [Rudolf Arend (1898-1980)--The forgotten first director of the Cracovian
      Neurology Clinic of the Medical Academy in the year 1950].

PMID- 17036514
TI  - Lung cancer mortality patterns in women resident in different urbanization areas
      in central Italy from 1987-2002.
AB  - AIMS AND BACKGROUND: The aim of the study was to evaluate mortality lung cancer
      trends, as an indicator of female smoking trends, in women resident in different
      urbanization areas. METHODS AND STUDY DESIGN: Data on the 5782 female lung cancer
      deaths that occurred in Tuscany, Italy, during the period 1987-2002 were
      analyzed, using age-period-cohort models by areas at different urbanization
      levels. Trends were examined with a log-linear regression model, calculating the
      yearly estimated percent change. Empirical bayesian estimators of the ratios
      between observed and expected deaths by municipality were calculated for the most
      recent period and mapped. RESULTS: The age-adjusted lung cancer mortality rates
      increased from 1987 to 2002: estimated percentage change values were equal to
      24.5% in the urban areas (P < 0.001) and 17.2% in the rural areas (P = 0.023).
      The age-period-cohort model analyses showed a statistically significant drift and
      non-linear cohort effects. The higher risk was observed for the birth cohort of
      women born around 1955 (RR, 5.25; 95% CI, 2.83-9.72). In the rural areas, no
      significant effects were observed, and the age model showed the best fit. In
      recent years, the risk appeared concentrated in 9 Tuscan municipalities,
      accounting more than 35% of the female urban population. CONCLUSIONS: The
      observed significant cohort effect in the age-period-cohort analyses for the
      urban areas reflects the social impact of living in these areas to induce smoking
      related disease like lung cancer in women. The risk appeared particularly
      relevant in more recent and urbanized generations (women born around 1955),
      thereby suggesting urgent effective campaigns against smoking, gender dedicated,
      especially in urban areas.

PMID- 17036515
TI  - Quality control of the autopap screening system employed as a primary screening
      device: rapid review of smears coded as no further review.
AB  - AIMS AND BACKGROUND: Automated reading of smears is increasingly used in cervical
      screening, and quality control procedures to check its performance are required.
      The aim of the present study was to evaluate the usefulness of rapid review of
      all smears coded as "no further review" (NFR) by the AutoPap system as a quality
      control procedure. METHODS: From 2002-2005, 153,269 smears were processed by
      AutoPap at the Centro per lo Studio e la Prevenzione Oncologica of Florence,
      Italy, and 24,503 (15.9%) were coded as NFR. All NFR smears underwent immediate
      rapid review by expert readers. RESULTS: Sixty-five of 118 NFR cases reviewed as
      ASCUS-R complied to recommended 6 months cytology, and 25 of 30 NFR cases
      reviewed as ASCUS-SIL or more severe accepted immediate colposcopy. As a result
      of such assessment, one single case of microinvasive carcinoma was detected in a
      woman aged 34 years: NFR smear had been reviewed as AGCUS, was followed by repeat
      AGCUS cytology and repeat negative colposcopy, and finally underwent conization.
      CONCLUSIONS: NFR report at AutoPap was associated with an extremely high negative
      predictive value, which might suggest using AutoPap as a primary screening tool,
      with NFR report prompting a "return to screening" recommendation. Rapid review of
      NFR smears is not recommended as a quality control measure for the negligible
      yield of high-grade lesions detected.

PMID- 17036516
TI  - Clinical presentation and treatment of gastrointestinal stromal tumors.
AB  - AIMS AND BACKGROUND: Gastrointestinal stromal tumors (GISTs), although rare, are
      the most common mesenchymal neoplasms affecting the gastrointestinal tract. We
      present our experience in the treatment of localized and metastatic disease and a
      review of literature. PATIENTS AND METHODS: Nine patients were observed from
      April 2002 to July 2004. Eight tumors were in the gastric area and 1 was in the
      small bowel. In 5 cases, complete surgical removal was performed, and none of
      these patients underwent adjuvant therapy. The remaining 4 cases, with locally
      advanced or recurrent disease, were treated with imatinib. RESULTS: The patients
      with localized disease treated only by surgery did not relapse. In the patients
      with locally advanced or metastatic disease treated by imatinib, we observed 3
      partial responses, and one case was not assessable because he had no measurable
      disease. In 2 of 3 responders, it was possible to perform a new radical surgery.
      CONCLUSIONS: Our series is too small to draw any conclusion. According to our
      review of the literature, surgery remains the standard treatment for non
      metastatic GISTs. Imatinib mesylate represents a major breakthrough in the
      treatment of advanced GISTs and is the first effective systemic therapy for the
      disease.

PMID- 17036517
TI  - Chemotherapy with mitomycin C and capecitabine in patients with advanced
      colorectal cancer pretreated with irinotecan and oxaliplatin.
AB  - AIMS AND BACKGROUND: To assess the activity and tolerability of the combination
      of mitomycin C and capecitabine in patients with metastatic colorectal cancer
      after failure of irinotecan and oxaliplatin-containing regimens. METHODS: We
      retrospectively reviewed 28 patients with pretreated advanced colorectal cancer
      who had been treated with mitomycin C, 6 mg/m2 on day 1, and capecitabine, 1900
      mg/m2 on days 1-14, every 3 weeks. Tumor assessment was performed every 3 cycles,
      toxicity assessed at each cycle. RESULTS: Main patient characteristics were
      median age, 61 years (range, 35-73); male/female ratio, 16/12; single metastatic
      site involvement, 5/28 (18%); > or =3 metastatic sites, 10/28 (36%). Ninety-six
      courses of therapy were given (median number, 3; range, 1-9). Twenty-six patients
      were assessable for response, and all were assessable for toxicity. There was 1
      partial response (4%) and 12 had stable disease (43%). Median time to progression
      was 2 months (range, 1-9) and median overall survival was 6 months (range, 1
      29+), with a 1-year overall survival rate of 25%. The regimen was very well
      tolerated without significant hematological toxicity. CONCLUSIONS: Our results
      are disappointing. Despite the good safety profile, they do not support further
      investigation or the routine use of this regimen in this setting.

PMID- 17036518
TI  - Single-agent irinotecan as second-line weekly chemotherapy in elderly patients
      with advanced colorectal cancer.
AB  - AIMS AND BACKGROUND: Irinotecan is a standard option for relapsed/refractory
      advanced colorectal cancer. Although in a recently reported, randomized trial it
      was found that a regimen of irinotecan once every 3 weeks was associated with a
      lower incidence of severe diarrhea than with weekly treatment with similar
      efficacy, there is no evidence in the literature that suggests the optimal dosing
      strategy for the drug, along with treatment efficacy and safety, following 5
      fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study
      has reported significantly reduced toxicity when irinotecan was administered once
      a week for 2 weeks, followed by a week rest. PATIENTS AND METHODS: From January
      2004 to April 2005, we analyzed, retrospectively, our data on single-agent
      irinotecan as a second-line chemotherapy in elderly patients (> or =70 years)
      with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80
      mg/m2) was given as a 60-min intravenous infusion in repeated 21-day courses
      comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest.
      Tumor measurements were obtained after every third course of therapy. Toxicity
      was assessed weekly using the National Cancer Institute Common Toxicity Criteria,
      version 2. RESULTS: The median number of treatment courses received per patient
      was 4 (range, 1-8). All patients were assessable for toxicity and 21 for
      response. The most frequently observed severe toxicities were diarrhea (grade 3,
      13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic
      fever occurred. Other hematological and non-hematological toxicities were mild
      and manageable. Objective partial responses were observed in 3 patients (13%). An
      additional 10 patients (43%) had stable disease as their best response. To date,
      12 patients have progressed with a median time-to-progression of 4.3 months and a
      median survival of 8.3 months. CONCLUSIONS: A weekly irinotecan administration
      can induce tumor control in elderly patients with advanced colorectal cancer that
      has progressed during or shortly after 5-fluorouracil/oxaliplatin-based
      chemotherapy. However, a careful monitoring of hematological toxicity and special
      instructions to prevent and manage diarrhea are mandatory in this setting of
      patients.

PMID- 17036519
TI  - Is radiation a risk factor for atherosclerosis? An echo-color Doppler study on
      Hodgkin and non-Hodgkin patients.
AB  - AIMS AND BACKGROUND: The aim of the present paper was to study the role of
      irradiation in the atherosclerotic process in patients affected by Hodgkin and
      non-Hodgkin lymphoma. METHODS: We studied 84 subjects, 42 with Hodgkin or non
      Hodgkin disease and 42 controls. All 42 cases had been irradiated and were
      comparable in terms of risk factors for atherosclerosis. All 84 subjects
      underwent echo-color Doppler of the arterial axis (carotids, abdominal aorta, and
      femoral arteries), and the intima-media thickness was measured. RESULTS: The
      irradiated cases had a greater intima-media thickness in the carotid district,
      even after dividing them according to age and sex; males were affected more than
      females. The irradiated patients were at greater risk of developing
      cardiovascular events than the controls. CONCLUSIONS: An echo-color Doppler of
      the carotid district is advisable in all patients who have been submitted to
      radiotherapy, and the patients with a significantly greater than normal intima
      media thickness need a strict follow-up, and antioxidant or antiaggregant therapy
      should be considered.

PMID- 17036520
TI  - Temozolomide and radiotherapy as first-line treatment of high-grade gliomas.
AB  - AIMS AND BACKGROUND: Temozolomide, a novel alkylating agent, has shown promising
      results in the treatment of patients with high-grade gliomas, when used as single
      agent as well as in combination with radiation therapy. MATERIALS AND METHODS: In
      this report we retrospectively reviewed the clinical outcome of 128 consecutive
      patients with a diagnosis of high-grade gliomas referred to our Institutions from
      April 1994 to November 2001. The first 64 patients were treated with radiotherapy
      alone and the other 64 with a combination of radiotherapy and temozolomide (31
      with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and
      concomitant temozolomide followed by adjuvant temozolomide). RESULTS: Grade 3
      hematological toxicity was scored in 9% of 64 patients treated with radiotherapy
      and temozolomide. No grade 4 hematological toxicity was reported, and the other
      acute side effects observed were mild or easily controlled with medications. Age,
      histology and administration of temozolomide were statistically significant
      prognostic factors associated with better 2-year overall survival. In contrast,
      we did not observe a significant difference in overall survival between adjuvant
      and concomitant/adjuvant temozolomide administration. CONCLUSIONS: We report the
      favorable results of a schedule combining radiotherapy and temozolomide in the
      treatment of patients with high-grade gliomas. The literature data and above all
      the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the
      schedule can be used routinely in clinical practice. Further clinical studies,
      using temozolomide in combination with other agents, are required.

PMID- 17036521
TI  - Assistance to parents who have lost their child with cancer.
AB  - AIMS AND BACKGROUND: To assess the psychological needs of parents after the death
      of their child from cancer. METHODS: The study comprises a preliminary
      retrospective phase to identify parents who spontaneously contacted the medical
      staff, followed by a prospective phase in which families were contacted by
      telephone and were invited to a meeting. RESULTS: The retrospective study
      demonstrated that more than 50% of the families spontaneously sought contact with
      the department. In the prospective study, 17 families were contacted and the
      majority of them subsequently decided to come to the department for a talk.
      CONCLUSIONS: Our experience shows that parents have a strong need to have further
      contact with the team that took care of their children for months. In the process
      of coping with bereavement, anxiety and depression are common and not necessarily
      pathological, though there may be psychopathological reactions that can interfere
      with the parents' quality of life.

PMID- 17036522
TI  - c-erbB-2 protein level in tissue and sera of breast cancer patients: a possibly
      useful clinical correlation.
AB  - AIMS AND BACKGROUND: The aims of this study were to assess the clinical utility
      of circulating preoperative HER-2 extracellular domain p105 detected by enzyme
      immunoassay (ELISA), to compare the tissue expression of HER-2/neu determined by
      immunohistochemistry (IHC), to correlate prognostic factors including tumor size,
      nodal involvement, and hormone receptor status, and to analyze the prognostic
      significance of the marker in relation to clinical outcome as measured by disease
      free and overall survival. METHODS: In this study, we enrolled 108 consecutive
      patients with breast carcinoma, and obtained serum samples and frozen tumor
      tissues. We compared them with 57 women with fibroadenoma and 63 healthy women as
      controls. RESULTS: Univariate ANOVA analysis showed no relationship between HER
      2/neu in tissue and serum. Preoperative serum levels of p105 were significantly
      higher in breast cancer patients than in women with benign disease or healthy
      women. Concerning the correlation between p105, HER-2/neu tissue expression, and
      the other prognostic factors, a statistically significant correlation between
      high serum p105 levels and ER-negative status in breast cancer patients was
      found. Kaplan-Meier analysis confirmed that patients with positive HER-2/neu
      tissue expression had a significantly shorter survival than those with negative
      expression. Analysis with the Cox model demonstrated that tumor size was the only
      significant independent prognostic factor. CONCLUSIONS: This research failed to
      demonstrate a relationship between preoperative tissue overexpression and
      circulating HER-2/neu, suggesting that p105 does not represent a valid
      alternative to predict a worsened prognosis in breast cancer, but it could be a
      diagnostic marker to discriminate healthy subjects from breast cancer patients.

PMID- 17036523
TI  - Urinary neopterin in patients with liver tumors.
AB  - AIMS AND BACKGROUND: Primary and secondary liver tumors are associated with poor
      prognosis. Neopterin is an indicator of systemic immune activation, and increased
      neopterin concentrations have been associated with poor prognosis in a wide range
      of malignant tumors. METHODS: Urinary neopterin was determined by high
      performance liquid chromatography in 154 patients with primary and secondary
      liver tumors. The survival of different groups of patients was compared by log
      rank test, and Cox regression was used for multivariate analysis. RESULTS:
      Urinary neopterin was significantly increased in patients compared to controls. A
      statistically significant correlation was observed between urinary neopterin and
      age of the patients, hemoglobin concentration, mean erythrocyte volume and
      peripheral blood leukocyte or platelet count. In univariate analysis, urinary
      neopterin below 214 micromol/mol creatinine, peripheral blood leukocytes below 8
      x 10(9)/L, hemoglobin equal to or above 125 g/L, no extrahepatic tumor, stage of
      liver involvement, and colorectal, breast or ovarian primary were significant
      prognostic factors for survival. In multivariate analysis, Bengtsson stage,
      presence of extrahepatic involvement, primary other than colorectal, breast or
      ovarian carcinoma, peripheral blood leukocyte count and urinary neopterin were
      independent prognostic factors. Increased urinary neopterin during and at the end
      of follow-up was also associated with poor prognosis. CONCLUSIONS: Urinary
      neopterin is increased in patients with liver tumors. Neopterin is an independent
      prognostic indicator in patients with liver tumors along with Bengtsson stage,
      presence of extrahepatic disease, primary site and peripheral blood leukocyte
      count.

PMID- 17036524
TI  - The correlation between TTF-1 immunoreactivity and the occurrence of lymph node
      metastases in patients with lung cancer.
AB  - AIMS AND BACKGROUND: Thyroid transcription factor (TTF-1) is a tissue-specific
      transcription factor expressed in the epithelial cells of thyroid and lung. The
      aim of this study was to evaluate the relationship between the expression of TTF
      1 and clinico-pathological parameters in pulmonary adenocarcinoma and
      adenosquamous carcinoma. METHODS: Resection material of pneumonectomies and
      lobectomies of 39 patients was retrospectively examined. Twenty-eight patients
      were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors
      were classified into 3 groups: a strongly positive group (++) with double dagger
      50% tumor cells positive for TTF-1; a weakly positive group (+) with 1-49%
      positive tumor cells; and a negative group (-) with less than 1% or no positive
      tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank
      tests. RESULTS: Staining for TTF-1 was negative in 10 cases. There was focal
      staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of
      39, and 15 (75%) of these were adenocarcinomas. There was a statistically
      significant association between TTF-1 and lymph node metastases (P = 0.029). No
      relationship was found between TTF-1 positivity and disease-free and overall
      survival. CONCLUSIONS: TTF-1 expression may be a predictor of lymph node
      metastases. Additional work in a larger group of patients is needed to better
      assess the utility of this marker.

PMID- 17036525
TI  - Combining independent studies of diagnostic fluorodeoxyglucose positron-emission
      tomography and computed tomography in mediastinal lymph node staging for non
      small cell lung cancer.
AB  - AIMS AND BACKGROUND: A meta-analysis of diagnostic test performance was conducted
      to compare the results of relevant studies reporting diagnostic accuracy values
      for mediastinal staging in patients with non-small cell lung cancer (NSCLC). This
      paper deals with the two most accurate imaging techniques currently in use:
      positron emission tomography (PET) with FDG and computed tomography (CT). A
      statistical pooling method was used to perform a quantitative meta-analysis aimed
      at demonstrating the potential advantage of one of these two methods. METHODS:
      Studies in all languages published between 1998 and 2005 that examined the use of
      FDG-PET and CT for mediastinal staging in NSCLC patients, enrolled at least 18
      participants, and provided enough data to allow calculation of sensitivity and
      specificity rates were considered eligible for the quantitative meta-analysis.
      Statistical methods to pool the overall estimates of sensitivity and specificity
      and to compare the discriminant power of PET and CT were discussed and used.
      RESULTS: Of the 13 studies included in the analysis, 12 reported greater accuracy
      of FDG-PET than CT in detecting mediastinal lymph node metastases. The
      sensitivity of FDG-PET ranged from 50% to 100%. The estimate of the overall
      sensitivity was 0.83% with 95% CI (0.749-0.913). Specificity ranged from 79% to
      100%, with an overall estimated specificity of 0.87% with 95% CI (0.80-0.95). For
      CT, the sensitivity and specificity ranged from 50% to 97% and 58% to 94%,
      respectively; the overall estimate was 0.68% with 95% CI (0.582-0.788) and 0.76%
      with 95% CI (0.668-0.859). The summary receiver operating characteristic (SROC)
      approach was used to assess the superior diagnostic accuracy of one of the two
      methods. The areas under the two SROC curves were AUC(PET) = 0.909 vs. AUC(CT) =
      0.794. CONCLUSIONS: Numerical and visual results of the meta-analysis of recent
      relevant reports agreed that FDG-PET is more accurate than CT in identifying
      mediastinal lymph node metastases in non-small cell lung cancer.

PMID- 17036526
TI  - Self-expanding metal stents in gastrointestinal interventional radiology:
      technical problems.
AB  - AIMS AND BACKGROUND: To analyze the procedural difficulties in the placement of
      metal stents in stenoses of the digestive tract and optimize the technique.
      METHODS: Twenty-nine patients with digestive tract stenoses were treated from
      January 1999 to December 2004. In 14 cases the stricture was anastomotic (9
      colorectal, 3 esophageal, 1 gastroesophageal and 1 gastrojejunal), in 13
      esophageal, in 1 gastric and in 1 duodenal. The stenosis was due to scarring in 5
      patients and was malignant in 24 patients (primary in 17 cases and secondary in 7
      cases). RESULTS: The procedure achieved technical success in all cases but 2. For
      each of the different segments the technical difficulties and the adopted
      procedural solutions were analyzed. CONCLUSIONS: The interventional radiology
      approach yielded results comparable to those reported for the endoscopic method
      and was always well tolerated. The need to rely on materials mostly designed for
      endoscopic use can make radiological use difficult in some cases.

PMID- 17036527
TI  - Phyllodes tumor with osteosarcomatous differentiation: a comparative
      immunohistochemical study between epithelial and mesenchymal cells.
AB  - AIMS AND BACKGROUND: Phyllodes tumor of the breast with osteosarcomatous
      differentiation is rare and very little is known about its molecular profile.
      METHODS AND STUDY DESIGN: An immunohistochemical panel with 37 primary antibodies
      including cytokeratins, mesenchymal markers, key regulators of the cell cycle,
      oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors
      was performed on a formalin-fixed paraffin-embedded sample of phyllodes tumor
      with osteosarcomatous differentiation in a 49-year-old woman. RESULTS:
      Antiapoptotic stimuli (survivin) predominated in sarcomatous cells.
      Antiproteolytic stimuli (TIMP-1, TIMP-2 and PAI) were preponderant in all cells,
      a surprising fact in view of the aggressiveness of the neoplasm. The
      immunoprofile of the osteoblastic and stromal cells was quite similar, except for
      c-erbB-3, c-myc, cyclin D1 and p21. Both exhibited positive cells for actin,
      MyoD1 and GFAP. CONCLUSIONS: Our results suggest that this osteosarcoma may have
      originated from metaplasia of stromal cells that underwent a malignant change.

PMID- 17036528
TI  - Cystic hygroma of the breast: a rare lesion.
AB  - Lymphangiomas are congenital malformations of lymphatic vessels. More than 50% of
      these lesions are present at birth; 90% are diagnosed by the age of 2. These
      lesions do not expand very rapidly but they tend to infiltrate surrounding
      tissues; their degeneration into malignant tumors is an extremely rare
      occurrence. They are mostly located in the neck region and the axilla; breast
      lymphangioma is very rare. Surgery is usually performed for aesthetic reasons and
      in order to make a differential diagnosis with other, more common lesions. The
      surgical procedure involves the excision of the mass; other methods, such as
      radiotherapy and sclerotherapy, have proved to be completely ineffective.

PMID- 17036529
TI  - Metastasis of giant cell tumor to the breast: case report and review of the
      literature.
AB  - Breast cancer is the most common type of malignancy in women. Of all breast
      cancers, 0.5-3% involve metastasis of a non-breast malignancy to the breast.
      Metastasis of soft tissue tumors to the breast is rarely seen. In particular,
      metastasis of a giant cell tumor to the breast has never been reported in the
      literature. We present here a case of breast metastasis in a 44-year-old woman
      with a diagnosis of malignant giant cell tumor originating from the distal radius
      and metastatic to the lung, who had been treated with radiotherapy, surgery and
      chemotherapy.

PMID- 17036530
TI  - Acute liver failure as the initial manifestation of hepatic infiltration by a
      solid tumor: report of 5 cases and review of the literature.
AB  - BACKGROUND: Acute liver failure is a rare complication of metastatic liver
      disease with a high mortality. Recognition of malignant infiltration of the liver
      as the cause of acute liver failure could be a diagnostic challenge. PATIENTS:
      The medical files of 5 patients with acute liver failure due to metastatic liver
      disease collected over a 4-year period (1997-2000) in our department were
      reviewed. RESULTS: No patient had a past history of cancer. The interval from
      jaundice to encephalopathy ranged from 7 to 12 days (median, 10). Physical
      examination revealed hepatomegaly and deep jaundice in all patients. AST
      elevation ranged from 147 to 1870 IU/L (median, 716 IU/L) and ALT elevation from
      74 to 556 IU/L (median, 138 IU/L). All patients died within 4-14 days (median, 7)
      of admission. None had papillary edema or decerebrate posture before death. Four
      patients had concurrent renal impairment. Liver imaging studies in 2 of the 5
      patients were nondiagnostic and the malignant liver infiltration was confirmed
      postmortem. Liver histology in all cases showed massive tumoral infiltration of
      the hepatic sinusoids with diffuse replacement of hepatocytes. The primary tumors
      were colon, gastric, small cell lung, pancreas and cancer of unknown origin.
      CONCLUSIONS: Malignant infiltration of the liver should be taken into account in
      the differential diagnosis of rapidly progressive liver failure. Although
      effective chemotherapy has improved the survival of patients with metastatic
      liver disease, there has been no change in the course and outcome of acute liver
      failure due to malignant infiltration of the liver over the last 2 decades. A
      proper diagnosis by liver biopsy is mandatory to prevent such patients from being
      considered for liver transplant.

PMID- 17036531
TI  - Multifocal biliary cystadenocarcinoma of the liver: CT and pathologic findings.
AB  - Biliary cystadenocarcinoma is a rare tumor that originates from the hepatobiliary
      epithelium. Although this tumor can affect any portion of the biliary tree,
      intrahepatic location is more common. It is usually a slow growing tumor and
      often asymptomatic until it reaches a considerable size. The lesion is most often
      solitary and large when discovered; multiple lesions or metastases within the
      liver are very rare. A 63-year-old man was referred to our institute for weight
      loss, abdominal discomfort, worsening bulky symptoms in the right upper abdominal
      quadrant, and an increase in serum aminotransferases that had been present for
      several months. Spiral CT of the abdomen demonstrated two lesions, a larger one
      and a distant intrahepatic lesion, with a multiloculated cystic aspect, a thin
      peripheral capsule, multiple solid peripheral portions, and irregular septa
      enhancing in the portal phase after intravenous administration of iodinated
      contrast medium. The diagnosis of multifocal cystadenocarcinoma of the liver was
      confirmed by surgical laparoscopy and biopsy of the lesion. The patient was
      treated with chemotherapy.

PMID- 17036532
TI  - Jaw avascular bone necrosis associated with long-term use of bisphosphonates.

PMID- 17036533
TI  - Overprotective caregivers of elderly cancer patients: a case report.
AB  - The essential role of the caregiver in the management of elderly cancer patients
      is still poorly documented. This case report concerns a woman with metastatic
      lung carcinoma who was sincerely informed and successfully treated with
      chemotherapy and gefitinib only after gaining the trust of her overprotective
      daughter. Devoting time to the relatives represents a key element to create a
      communicative and efficient relationship with older cancer patients.

PMID- 17036534
TI  - Safety of epirubicin adjuvant chemotherapy in a breast cancer patient with
      chronic renal failure undergoing hemodialytic treatment.
AB  - Anthracycline-based adjuvant chemotherapy is very effective in early breast
      cancer, but there are limited data on the use of epirubicin in patients with
      chronic renal failure undergoing hemodialytic treatment. We report the case of a
      patient with early breast cancer and chronic renal failure who was treated with
      adjuvant weekly epirubicin. Treatment was well tolerated. The patient is still
      alive and relapse free 58 months after surgery. If the patient will be disease
      free after 5 years, she will be reconsidered for renal transplantation. In
      conclusion, weekly epirubicin appears to be a safe adjuvant chemotherapy option
      for early breast cancer patients with chronic renal failure undergoing
      hemodialytic treatment.

PMID- 17036535
TI  - A case of bone involvement in hairy cell leukemia successfully treated with
      radiation therapy.
AB  - We report the case of a 63-year-old man with a clearly established diagnosis of
      hairy cell leukemia, treated with multiple lines of chemotherapy, who complained
      of localized pain in the left humerus. Radiological findings showed a dystrophic
      blastic area within the humeral head. Fine-needle biopsy confirmed the hypothesis
      of bone involvement of hairy cell leukemia. The patient underwent radiotherapy at
      a dose of 25 Gy, obtaining a complete clinical response with resolution of pain
      and a partial recovery of the normal radiological structure of the humerus after
      2 months. In addition to the case report, we present a short review of the
      literature focusing on the role of radiotherapy in this subset of patients.

PMID- 17036536
TI  - [ASCO 2006. Exemestane: a new drug for the adjuvant therapy of breast cancer].

PMID- 17036537
TI  - [ASCO 2006 Annual Meeting, Atlanta, June 2-6, 2006. Focus on gastrointestinal
      tumors].

PMID- 17036538
TI  - Pediatric caries worldwide: implications for oral hygiene products.
AB  - International data on pediatric caries epidemiology confirms that tooth decay
      remains a significant and consequential disease of childhood that is increasingly
      localized in a subset of at-risk children in both developing and developed
      countries. A conceptual schema is presented to characterize the occurrence of
      caries in child populations, and observations are made regarding the
      countervailing impact of simple sugars and fluoride in these populations.
      Temporal changes in caries distribution suggest that targeted dental caries
      management protocols are increasingly indicated to more effectively manage the
      particular risk and caries activity of individual children. Criteria for
      successful protocols are discussed in light of both caries pathogenesis and
      international recommendations to improve children's oral health.

PMID- 17036539
TI  - Dental caries: an infectious and transmissible disease.
AB  - By definition, dental caries is an infectious and transmissible disease because
      it is caused by bacteria colonizing the tooth surfaces. Unlike most infectious
      diseases affecting humans, caries is the result of an imbalance of the indigenous
      oral biota rather than a nonindigenous, exogenous pathogen. The introduction of
      refined sugar into modern society's diet has tipped the balance from health to
      disease. New insight into the natural history of the leading cariogenic bacteria,
      the mutans streptococci, may contribute ways to control or prevent this
      infectious disease. Here, we use the host-parasite model as a platform for
      viewing the pathogenicity of the caries process in contrast to other infectious
      diseases.

PMID- 17036540
TI  - Clinical considerations for an infant oral health care program.
AB  - The American Academy of Pediatric Dentistry and the American Association of
      Pediatrics recommend dental assessments and evaluations for children during their
      first year of life. Early dental intervention evaluates a child's risk status
      based on parental interviews and oral examinations. These early screenings
      present an opportunity to educate parents about the medical, dental, and cost
      benefits of preventive--rather than restorative-care and may be more effective in
      reducing early childhood caries than traditional infectious disease models. A
      comprehensive infant oral care program includes: (1) risk assessments at
      regularly scheduled dental visits; (2) preventive treatments such as fluoride
      varnishes or sealants; (3) parental education on the correct methods to clean the
      baby's mouth; and (4) incentives to encourage participation in ongoing
      educational programming. Recruiting mothers during pregnancy improves the
      likelihood that they will participate in the assessment program. To maximize
      interest, trust, and success among participating parents, educational and
      treatment programs must be tailored to the social and cultural norms within the
      community being served.

PMID- 17036541
TI  - Early dental caries detection as a part of oral health maintenance in young
      children.
AB  - There is an ever-growing need to manage the results of dental caries in young
      children. Other articles in this supplement discuss age-specific recommendations
      regarding caries management in children. This article will introduce the idea of
      using technology to assess caries risk in children and also will identify
      alternative technologies that could be used to detect caries lesions as early as
      possible. It is hoped that by learning about some of the new technologies that
      can be used in caring for children's dental needs, a new cadre of general
      practitioners will be willing to take on a portion of the important role of
      caring for our children.

PMID- 17036542
TI  - Oral health promotion in children and adolescents.
AB  - One of the primary goals of dental health professionals is to prevent disease in
      our patients. As our knowledge of the disease process improves, so does our
      ability to manage the consequences of disease. Oral diseases, such as dental
      caries, can be devastating to both children and adolescents. Dental caries may
      interfere with a child's ability to eat, sleep, and learn, and it can have a
      significant impact on their self-esteem. Because caries affects individuals
      disproportionately, it is essential that those at the highest risk are identified
      early so that preventive therapies can be targeted toward those who are most
      likely to benefit. This article discusses the consequences of oral diseases in
      school-aged children, the factors that contribute to an individual's risk for
      dental caries, and the most effective therapies to prevent caries in this age
      group.

PMID- 17036543
TI  - Consumer assessment of toothbrushes designed for children of different ages.

PMID- 17036544
TI  - Intergenerational social mobility: the United States in comparative perspective.
AB  - Emily Beller and Michael Hout examine trends in U.S. social mobility, especially
      as it relates to the degree to which a person's income or occupation depends on
      his or her parents' background and to the independent contribution of economic
      growth. They also compare U.S. social mobility with that in other countries. They
      conclude that slower economic growth since 1975 and the concentration of that
      growth among the wealthy have slowed the pace of U.S. social mobility. In
      measuring mobility, economists tend to look at income and sociologists,
      occupation. The consensus among those measuring occupational mobility is that the
      average correlation between the occupations of fathers and sons today ranges from
      0.30 to 0.40, meaning that most variation in the ranking of occupations is
      independent of social origins. Those measuring income mobility tend to agree that
      the elasticity between fathers' and sons' earnings in the United States today is
      about 0.4, meaning that 40 percent of the difference in incomes between families
      in the parents' generation also shows up in differences in incomes in the sons'
      generation. Beller and Hout show that occupational mobility increased during the
      1970s, compared with the 1940s-1960s, but there is some evidence to suggest that
      by the 1980s and 1990s it had declined to past levels. Existing data on income
      mobility show no clear trends over time, but increases in economic inequality
      during the 1980s made mobility more consequential by making economic differences
      between families persist for a longer time. In international comparisons, the
      United States occupies a middle ground in occupational mobility but ranks lower
      in income mobility. Researchers have used the variation in mobility to study
      whether aspects of a country's policy regime, such as the educational or social
      welfare systems, might be driving these results. There is as yet, however, no
      scholarly consensus about the sources of cross-national differences in mobility.

PMID- 17036545
TI  - Intergenerational mobility for women and minorities in the United States.
AB  - Now that some of the historic barriers to economic success for U.S. women and
      minorities have begun to fall, women and blacks, in particular, are moving upward
      on the nation's socioeconomic ladder. Melissa Kearney reviews evidence that
      improved economic opportunities for these two groups make sex and race less
      important than they once were in determining economic status. But sex- and race
      based differences in wages and income persist, and interactions between sex and
      class and between race and class continue to play a role in the intergenerational
      transmission of income status. Kearney surveys studies and data showing that
      marriage remains important in determining women's economic status, even though
      marriage rates among women aged eighteen to thirty-four have been falling--from
      73 percent in 1960 to 44 percent in 2000. Not only do spousal earnings continue
      to dominate family income for married women, but also women tend to marry men
      whose position in the income distribution resembles their fathers' position.
      Marriage thus facilitates the transmission of economic status from parents to
      daughters. Racial wage gaps persist, says Kearney, largely because of differences
      in education, occupation, and skill. It also appears likely that the effects of
      discrimination, both current and past, continue to impede racial economic
      convergence. Kearney notes that the transmission of income class from parents to
      children among blacks differs noticeably from that among whites. Black parents
      and white parents pass their economic standing along to children at similar
      rates. But because mean income is lower among blacks than among whites, the
      likelihood of upward mobility in the overall income distribution is substantially
      lower among blacks. Black children are much more likely than white children to
      remain in the lower percentiles of the income distribution, and white children
      are more likely to remain in the upper reaches of the income distribution.
      Downward mobility from the top quartile to the bottom quartile is nearly four
      times as great for blacks as for whites.

PMID- 17036546
TI  - Making it in America: social mobility in the immigrant population.
AB  - In his survey of research on social mobility and U.S. immigration, George Borjas
      underscores two insights. First, most immigrants are at a sizable earnings
      disadvantage, relative to native-born workers. Second, the earnings of different
      groups of immigrants vary widely. The children of immigrants "catch up" to native
      born workers slowly. The jump in relative wages between the first and second
      generations is somewhere between 5 and 10 percentage points. Of particular
      concern is that the age-adjusted relative wage of both immigrants and second
      generation workers has been falling--a trend with bleak implications for the
      children of immigrants. The wide ethnic variation in the earnings of immigrants
      has equally important implications. National origin groups from advanced
      economies, such as Canada, do much better in the U.S. labor market than those
      from poorer countries, such as Mexico. And the initial ethnic differences tend to
      persist. In rough terms, about half of the difference in relative economic status
      persists from one generation to the next. Thus a 20 percentage point wage gap
      among ethnic groups in the immigrant generation implies a 10 point gap among
      second-generation groups and a 5 point gap among third-generation groups. Again
      in rough terms, Borjas attributes about half of that persistence to the ethnic
      environment in which children are raised. Borjas cautions that the rate of social
      mobility that immigrants enjoyed over much of the twentieth century may not
      continue in the future. The employment sectors seeking immigrants today are
      unlikely to provide the same growth opportunities as did the rapidly expanding
      manufacturing sector a century ago. And in contrast to the many and diverse
      ethnic groups that made up early twentieth-century immigrants, the large ethnic
      groups of immigrants today may develop separate economies and social structures,
      in effect hindering their social mobility.

PMID- 17036547
TI  - Early childhood development and social mobility.
AB  - Steven Barnett and Clive Belfield examine the effects of preschool education on
      social mobility in the United States. They note that under current policy three-
      and four-year-old children from economically and educationally disadvantaged
      families have higher preschool attendance rates than other children. But current
      programs fail to enroll even half of poor three- and four-year-olds. Hispanics
      and children of mothers who drop out of school also participate at relatively low
      rates. The programs also do little to improve learning and development. The most
      effective programs, they explain, are intensive interventions such as the model
      Abecedarian and Perry Preschool programs, which feature highly qualified teachers
      and small group sizes. State preschool programs with the highest standards rank
      next, followed by Head Start and the average state program, which produce effects
      ranging from one-tenth to one-quarter of those of the best programs. Typical
      child care and family support programs rank last. Barnett and Belfield point out
      that preschool programs raise academic skills on average, but do not appear to
      have notably different effects for different groups of children, and so do not
      strongly enhance social mobility. In such areas as crime, welfare, and teen
      parenting, however, preschool seems more able to break links between parental
      behaviors and child outcomes. Increased investment in preschool, conclude Barnett
      and Belfield, could raise social mobility. Program expansions targeted to
      disadvantaged children would help them move up the ladder, as would a more
      universal set of policies from which disadvantaged children gained
      disproportionately. Increasing the educational effectiveness of early childhood
      programs would provide for greater gains in social mobility than increasing
      participation rates alone. The authors observe that if future expansions of
      preschool programs end up serving all children, not just the poorest, society as
      a whole would gain. Benefits would exceed costs and there would be more economic
      growth, but relative gains for disadvantaged children would be smaller than
      absolute gains because there would be some (smaller) benefits to other children.

PMID- 17036548
TI  - U.S. elementary and secondary schools: equalizing opportunity or replicating the
      status quo?
AB  - Although education pays off handsomely in the United States, children from low
      income families attain less education than children from more advantaged
      families. In this article, Cecilia Elena Rouse and Lisa Barrow investigate why
      family background is so strongly linked to education. The authors show that
      family socioeconomic status affects such educational outcomes as test scores,
      grade retention, and high school graduation, and that educational attainment
      strongly affects adult earnings. They then go on to ask why children from more
      advantaged families get more or better schooling than those from less advantaged
      families. For low-income students, greater psychological costs, the cost of
      forgone income (continuing in school instead of getting a job), and borrowing
      costs all help to explain why these students attain less education than more
      privileged children. And these income-related differences in costs may themselves
      be driven by differences in access to quality schools. As a result, U.S. public
      schools tend to reinforce the transmission of low socioeconomic status from
      parents to children. Policy interventions aimed at improving school quality for
      children from disadvantaged families thus have the potential to increase social
      mobility. Despite the considerable political attention paid to increasing school
      accountability, as in the No Child Left Behind Act, along with charter schools
      and vouchers to help the children of poor families attend private school, to date
      the best evidence suggests that such programs will improve student achievement
      only modestly. Based on the best research evidence, smaller class sizes seem to
      be one promising avenue for improving school quality for disadvantaged students.
      High teacher quality is also likely to be important. However, advantaged
      families, by spending more money on education outside school, can and will partly
      undo policy attempts to equalize school quality for poor and nonpoor children.

PMID- 17036549
TI  - The role of higher education in social mobility.
AB  - Most Americans expect the nation's colleges and universities to promote the goal
      of social mobility to make it possible for anyone with ability and motivation to
      succeed. But according to Robert Haveman and Timothy Smeeding, income-related
      gaps both in access to and in success in higher education are large and growing.
      In the top-tier colleges and universities, almost three-quarters of the entering
      class is from the highest socioeconomic quartile. The pool of qualified youth is
      far greater than the number admitted and enrolled; hence America's top colleges
      could enroll more moderate- and low-income students without lowering their
      selection standards. Higher-income parents make enormous efforts to ensure their
      children's academic success, while children of poor parents begin the "college
      education game" later and with fewer resources. Students in poor and minority
      neighborhoods are less well prepared academically; ill prepared to select
      colleges, apply for admission, and secure acceptance; and poorly informed about
      the cost of attending college and the availability of needs-based financial aid.
      Sharply rising college prices during the 1980s and 1990s, together with the
      growing inequality of family income, have raised the cost of attending college
      far more for low-income students than for well-to-do students. Financial aid has
      risen more slowly, and the share targeted on low-income students has been
      falling. The authors offer bold policy recommendations to increase educational
      opportunities for low- and middle-income students. These involve the development
      of financing structures that will increase access for students from lower-income
      families. Public institutions could price tuition close to real costs and use
      added revenues to provide direct student aid for students from low-income
      families. Federal subsidies to students who attend wealthy institutions could be
      capped, with the savings redirected to students attending less well-endowed
      schools, both public and private. Finally, federal and state governments could
      redirect to lower-income students the financial support they now provide colleges
      and universities.

PMID- 17036550
TI  - Children's health and social mobility.
AB  - Children from low-income families are more likely than other children to have
      serious health problems. And, as Anne Case and Christina Paxson show, childhood
      health problems can prevent poor children from achieving economic success as
      adults. Income-related disparities in childhood health are evident at birth or
      even before, and the disparities grow more pronounced as children grow older. Not
      only do poor children have more severe health problems than wealthier children,
      but they fare less well than wealthier children who have the same problems. They
      also receive less and lower-quality medical care for their problems. And poor
      families may be less well equipped to manage their children's health problems,
      which could worsen their effects. The available U.S. data sets do not allow
      researchers to track individuals' health and economic well-being from birth into
      adulthood, but three British data sets are producing growing evidence that health
      in childhood is a determinant of educational attainment, which in turn affects
      adults' employment opportunities and wages. Children in poor health are also more
      likely to have poor health as adults, and their health as adults adversely
      affects their economic status. Case and Paxson note that eliminating income
      related disparities in health problems in childhood would do little to reduce
      earnings disparities between richer and poorer adults. However, they emphasize
      that, for children in poor health, improvement in physical condition in childhood
      would lead to substantial improvement in economic circumstances. The authors cite
      several areas, including expanded prenatal care, maternal smoking cessation
      programs, and nutrition programs, as deserving particular attention. They contend
      that increased access to health care is not sufficient to improve children's
      health. The next wave of policies should focus on improving the quality of health
      care and strengthening the ability of parents to manage their children's health
      problems.

PMID- 17036551
TI  - "Culture" and the intergenerational transmission of poverty: the prevention
      paradox.
AB  - Many U.S. policymakers support changing the "culture" of poor parents to
      encourage marriage, work, and religion as a means to end the intergenerational
      transmission of poverty. In this article Jens Ludwig and Susan Mayer review and
      evaluate research on how parental work, marriage, and religion affect children's
      socioeconomic status as adults, as well as on the likelihood that changing these
      indicators of parental behavior will reduce poverty in the next generation. They
      conclude that even if policymakers were able to ensure that all children had
      married, working, and religious parents, the result would be a far smaller
      reduction in poverty among the children's generation than many people believe.
      The explanation for this "poverty-prevention paradox," say Ludwig and Mayer, is
      that the poverty rate in the children's generation depends not only on how many
      poor children grow up to be poor adults, but also on how many nonpoor children
      grow up to be poor adults. Reducing the chances that poor children become poor
      adults will dramatically lower future poverty rates only if most poor adults
      begin life as poor children. But most poor adults grow up as nonpoor children in
      the type of "pro-social" households that policymakers are pushing to attain.
      Moreover, little good evidence supports the idea that such parental behaviors as
      marriage, work, and religious adherence have strong causal effects on children's
      long-term economic success. The authors argue that encouraging positive social
      behaviors in the parents of poor children is a worthwhile goal in its own right.
      But they stress that policymakers should recognize the limits of this strategy
      for reducing poverty among future generations. There may be no substitute for a
      system of social insurance and income transfers for those children who do wind up
      poor as adults.

PMID- 17036552
TI  - Benign intrapulmonary teratoma.

PMID- 17036553
TI  - Oral contraceptive use and breast cancer risk: current status.

PMID- 17036554
TI  - Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta
      analysis.
AB  - OBJECTIVE: To perform a meta-analysis of case-control studies that addressed
      whether prior oral contraceptive (OC) use is associated with premenopausal breast
      cancer. METHODS: We searched the MEDLINE and PubMed databases and bibliography
      reviews to identify case-control studies of OCs and premenopausal breast cancer
      published in or after 1980. Search terms used included breast neoplasms, oral
      contraceptives, contraceptive agents, and case-control studies. Studies reported
      in all languages were included. Thirty-four studies were identified that met
      inclusion criteria. Two reviewers extracted data from original research articles
      or additional data provided by study authors. We used the DerSimonian-Laird
      method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the
      Mantel-Haenszel test to assess association between OC use and cancer. RESULTS:
      Use of OCs was associated with an increased risk of premenopausal breast cancer
      in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use.
      Among studies that provided data on nulliparous and parous women separately, OC
      use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20
      1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use
      did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85
      1.96). Among parous women, the association was stronger when OCs were used before
      first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP
      (OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer
      risk was greatest for parous women who used OCs 4 or more years before FFTP (OR,
      1.52; 95% CI, 1.26-1.82). CONCLUSION: Use of OCs is associated with an increased
      risk of premenopausal breast cancer, especially with use before FFTP in parous
      women.

PMID- 17036555
TI  - Pyridostigmine, diethyltoluamide, permethrin, and stress: a double-blind,
      randomized, placebo-controlled trial to assess safety.
AB  - OBJECTIVE: To determine whether short-term human exposure to pyridostigmine
      bromide, diethyltoluamide, and permethrin, at rest or under stress, adversely
      affects short-term physical or neurocognitive performance. PARTICIPANTS AND
      METHODS: A multicenter, prospective, double-blind, placebo-controlled crossover
      trial exposing 64 volunteers to permethrin-impregnated uniforms, diethyltoluamide
      containing skin cream, oral pyridostigmine, and corresponding placebos was
      performed. Each participant had 4 separate sessions, ensuring exposure to all
      treatments and placebos under both stress and rest conditions in random order.
      Outcomes Included physical performance (handgrip strength and duration, stair
      climbing, and pull-ups [males] or push-ups [females]), neurocognitive performance
      (computerized tests), and self-reported adverse effects. RESULTS: Permethrin was
      undetectable in the serum of all participants; pyridostigmine levels were higher
      Immediately after stress (41.6 ng/mL; 95% confidence Interval, 35.1-48.1 ng/mL)
      than rest (23.0 ng/mL; 95% confidence Interval, 19.2-26.9 ng/mL), whereas
      diethyltoluamide levels did not significantly differ by stress condition. Heart
      rate and systolic blood pressure increased significantly with stress compared
      with rest but did not vary with treatment vs placebo. Physical and neurocognitive
      outcome measures and self-reported adverse effects did not significantly differ
      by exposure group. CONCLUSION: Combined, correct use of pyridostigmine,
      diethyltoluamide, and permethrin is well tolerated and without evidence of short
      term physical or neurocognitive impairment.

PMID- 17036556
TI  - Assessing the ability of topiramate to improve the daily activities of patients
      with migraine.
AB  - OBJECTIVE: To assess the impact of topiramate on the daily activities of patients
      with migraine. PATIENTS AND METHODS: We performed a randomized, double-blind,
      placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on
      April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire
      (MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36)
      were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat
      population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two
      activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention [MSQ
      RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and vitality
      [SF36-VT]) were the prospectively designated secondary outcome measures. The
      changes in MSQ and SF-36 scores for each treatment group were calculated by
      measuring the area under the curve from week 8 (the beginning of the maintenance
      period) through week 26 of the double-blind phase, relative to the prospective
      baseline. A mixed-effect piecewise linear regression model was used to estimate
      average domain score over time. RESULTS: Patients receiving topiramate, 100 or
      200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P =
      .008 and P < .001, respectively) compared with placebo, but not patients
      receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean
      MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P <
      .001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001],
      and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly
      improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses)
      improved SF36-VT domain scores, although not significantly vs placebo. Changes in
      prospectively designated domain scores were significantly correlated with changes
      in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002
      [SF-36 domains]). CONCLUSION: Patient-reported migraine-specific outcomes
      measured by the MSQ-RR and MSQ-RP domains improved significantly for those
      receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved
      significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements
      in all 4 prospectively selected MSQ and SF-36 domains were significantly
      correlated with decreases in mean monthly migraine frequency.

PMID- 17036557
TI  - Effect of valacyclovir on viral shedding in immunocompetent patients with
      recurrent herpes simplex virus 2 genital herpes: a US-based randomized, double
      blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine the efficacy of daily suppressive therapy with a 1-g dose
      of valacyclovir in reducing total (clinical and subclinical) herpes simplex virus
      2 (HSV-2) shedding compared with placebo in Immunocompetent patients diagnosed as
      having recurrent HSV-2 genital herpes. PATIENTS AND METHODS: From June 18, 2004,
      to December 17, 2004, patients from 27 US sites with a history of 6 or more
      genital herpes recurrences per year were randomized in a 3:1 ratio to receive 1
      g/d of valacyclovir or placebo. During the double-blind suppressive therapy,
      patients were provided with the study drug (500-mg valacyclovir caplets or
      matching placebo) and Instructed to take 2 caplets once daily without regard to
      meals for 60 days. Daily genital and anal or rectal swabs were self-collected
      during the 60-day study period for evaluation of HSV-2 viral shedding as
      determined by quantitative type-specific polymerase chain reaction assay.
      RESULTS: One hundred fifty-two patients were randomized into this study, 43 to
      placebo and 109 to 1 g/d of valacyclovir. A total of 134 completed the study (40
      placebo [93%], 94 valacyclovir [86%]), and 18 prematurely withdrew (3 placebo
      [7%], 15 valacyclovir [14%]). Valacyclovir significantly reduced the percentage
      of days with total (clinical and subclinical) HSV-2 shedding throughout 60 days
      compared with placebo. In the intent-to-treat population, a 71% reduction in
      total shedding (P < .001), a 58% reduction in subclinical shedding (P < .001),
      and a 64% reduction in clinical shedding (P = .01) were observed. Valacyclovir
      was not associated with any significant toxic effects compared with placebo.
      CONCLUSION: This study demonstrated that 1 g/d of valacyclovir administered for
      60 days was generally well tolerated and was an effective suppressive therapy
      that significantly reduced total (clinical and subclinical) HSV-2 shedding
      compared with placebo in immunocompetent patients diagnosed as having recurrent
      HSV-2 genital herpes.

PMID- 17036558
TI  - Coverage of coma in headlines of US newspapers from 2001 through 2005.
AB  - OBJECTIVE: To review journalists' preferences and accuracy in reporting comatose
      states. METHODS: Using the Lexis-Nexis database, we selected newspaper headlines
      from January 1, 2001, through December 31, 2005, that included the words coma,
      comatose, unconsciousness, vegetative state, awakening, and brain dead. RESULTS:
      We identified 340 stories by headlines. The median age of persons in coma was 26
      years. Coma cases in men were twice as common as those in women. In 71% of coma
      cases, the cause of coma was associated with motor vehicle crashes or violence.
      Persistent vegetative state was reported in 25 articles (7%), frequently when a
      family or physician conflict emerged. In 33 stories (10%), coma was medically
      induced but not mentioned in the headline. Three "miracle" recoveries involved
      resumption of speech in patients in a minimally conscious state. CONCLUSION: Few
      news reports had gross inaccuracies or misrepresentations; however, definitional
      difficulties of unconscious states with the reporters remain. The reporting of
      coma may be biased toward violence and trauma. Medically induced coma was present
      in 1 of 10 reports but rarely mentioned in the headline.

PMID- 17036559
TI  - Extradigital glomus tumors: a 20-year experience.
AB  - OBJECTIVE: To review a large series of extradigital glomus tumors in order to
      gain a better understanding of their presentation and provide guidelines to aid
      in their diagnosis and treatment. PATIENTS AND METHODS: We performed a
      retrospective review of all extradigital glomus tumors seen at our institution
      during a 20-year period (1985-2005) to document the incidence of the classic
      triad of symptoms, the duration of symptoms, the contribution of imaging to
      making a definitive diagnosis, and the effectiveness of treatment. RESULTS: Fifty
      six different patients with extradigital glomus tumors presented as follows:
      glomus tumors in the hand (3), wrist (4), forearm (11), elbow (4), arm (4),
      shoulder (2), buttock (1), thigh (5), knee (10), leg (3), ankle (2), foot (2),
      back (1), nose (1), cheek (1), ear lobe (1), and trachea (1). Forty-eight
      patients presented with pain and localized tenderness, but only 1 patient
      presented with cold Intolerance. The average duration of symptoms was greater
      than 7 years, with most patients being evaluated previously and having their
      conditions misdiagnosed. Magnetic resonance imaging proved to be the most useful
      modality for localization of these lesions. Surgical resection was the definitive
      treatment and generally provided immediate and sustained pain relief.
      CONCLUSIONS: Extradigital glomus tumors are not a rare subgroup of glomus tumors.
      Treatment outcomes are excellent, but misdiagnosis and delayed diagnosis are
      common. Improved guidelines regarding symptoms and diagnosis of these neoplasms
      may reduce the morbidity, ensuing chronic pain, and psychiatric consequences of
      delayed diagnosis or misdiagnosis.

PMID- 17036560
TI  - Prevalence of restless legs syndrome among native South Americans residing in
      coastal and mountainous areas.
AB  - OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native
      South Americans and identify the impact of geographic location. PARTICIPANTS AND
      METHODS: An epidemiological telephone survey of RLS symptoms involving natives
      from coastal and mountainous areas was performed during July 2, 2004, through
      September 28, 2004. The process consisted of 2 phases: the creation of the
      epidemiological instrument and the telephone survey. RESULTS: Five hundred
      adults, 250 from the mountainous regions and 250 from the coastal region (190 men
      and 310 women; age range, 25-85 years) were interviewed and subsequently divided
      on the basis of International Restless Legs Syndrome Study Group criteria into
      those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had
      RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m
      above sea level (3.2% [8/250]) was significantly higher than that for adults
      living in the coastal region at 4 m above sea level (0.80% [2/250]; P = .002).
      The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-85
      years). CONCLUSION: Native South American adults have a prevalence of RLS well
      below that reported in populations with European ancestry but similar to that in
      Asian and Turkish populations. Furthermore, in Ecuador, geographic differences
      were identified in areas of similar population density.

PMID- 17036562
TI  - Psychiatric adverse effects of corticosteroids.
AB  - Psychiatric adverse effects during systemic corticosteroid therapy are common.
      Two large meta-analyses found that severe reactions occurred in nearly 6% of
      patients, and mild to moderate reactions occurred in about 28%. Although
      disturbances of mood, cognition, sleep, and behavior as well as frank delirium or
      even psychosis are possible, the most common adverse effects of short-term
      corticosteroid therapy are euphoria and hypomania. Conversely, long-term therapy
      tends to induce depressive symptoms. Dosage is directly related to the incidence
      of adverse effects but is not related to the timing, severity, or duration of
      these effects. Neither the presence nor the absence of previous reactions
      predicts adverse responses to subsequent courses of corticosteroids.
      Corticosteroid-induced symptoms frequently present early in a treatment cycle and
      typically resolve with dosage reduction or discontinuation of corticosterolds. In
      severe cases or situations in which the dose cannot be reduced, antipsychotics or
      mood stabilizers may be required. This review offers an approach to identifying
      and managing corticosteroid-induced psychiatric syndromes based on the type of
      symptoms and anticipated duration of corticosteroid treatment.

PMID- 17036561
TI  - Use of antidementia agents in vascular dementia: beyond Alzheimer disease.
AB  - Vascular dementia (VaD) is the second leading cause of dementia and is often
      underdiagnosed. Stroke is the leading cause of VaD, although it may also develop
      secondary to a variety of other cerebrovascular or cardiovascular conditions.
      Currently, no drugs are approved for the treatment of VaD. However, because
      cholinergic deficits have been found in patients with VaD, similar to those found
      in patients with Alzheimer disease (AD), it is believed that cholinesterase
      inhibitors, which are indicated for the treatment of mild to moderate AD, may
      also provide benefit for patients with VaD. Clinical trials of donepezil,
      galantamine, and rivastigmine have supported this idea, although as yet, large
      scale, prospective studies in VaD have only been reported for donepezil.
      Donepezil was shown to provide benefits in cognition, global function, and
      activities of daily living compared with placebo. The N-methyl-D-aspartate
      receptor antagonist memantine may also provide some cognitive benefit in VaD,
      particularly in patients with more advanced disease. These data suggest that
      antidementia drugs currently used for treatment of AD should be considered for
      treatment of VaD as well.

PMID- 17036563
TI  - Copper deficiency myelopathy (human swayback).
AB  - The hematologic manifestations of copper deficiency are well known and include
      anemia and neutropenia. In the past few years, the neurological manifestations of
      acquired copper deficiency in humans has been recognized, the most common being a
      myelopathy presenting with a spastic gait and prominent sensory ataxia. The known
      causes of acquired copper deficiency include prior gastric surgery, excessive
      zinc ingestion, and malabsorption; however, often the cause is unclear.
      Hyperzincemia may be present even in the absence of exogenous zinc ingestion. The
      clinical features and neuroimaging findings are similar to the subacute combined
      degeneration seen in patients with vitamin B12 deficiency. Copper and vitamin B12
      deficiency may coexist. The neurological syndrome may be present without the
      hematologic manifestations. Copper supplementation resolves the anemia and
      neutropenia promptly and completely and may prevent the neurological
      deterioration. Improvement, when it occurs, is often subjective and
      preferentially involves sensory symptoms. This article describes patients with
      copper deficiency myelopathy seen at the Mayo Clinic in Rochester, Minn, and
      reviews the literature on neurological manifestations of acquired copper
      deficiency in humans.

PMID- 17036565
TI  - 37-year-old woman with headache.

PMID- 17036564
TI  - Answers to frequently asked questions about migraine.
AB  - Migraine is a common primary headache disorder associated with pronounced
      disability and hence marked economic and public health Implications. Appropriate
      treatment is warranted to limit the associated disability migraineurs experience.
      Because of the heterogeneity of migraine, treatment plans must be individualized.
      The purpose of this article is to provide answers to frequently asked questions
      regarding the management of migraine.

PMID- 17036566
TI  - Tumor lysis syndrome associated with reduced immunosuppression in a lung
      transplant recipient.
AB  - Tumor lysis syndrome usually occurs after Initiation of chemotherapy or radiation
      therapy in cancer patients with a moderate to high tumor burden. To our
      knowledge, the occurrence of this syndrome after discontinuation or reduction of
      an immunosuppressive regimen has not been reported in the literature. We describe
      a patient who had undergone lung transplantation and who was receiving
      immunosuppression and experienced an episode of acute pancreatitis. During the
      course of the work-up, the patient was found to have a B-cell lymphoma
      (posttransplantation lymphoproliferative disease). His tacrolimus dosage was
      decreased, and azathioprine was discontinued. The patient subsequently developed
      tumor lysis syndrome. Other than the decrease in immunosuppression, we found no
      other factor that could have accounted for this syndrome.

PMID- 17036567
TI  - The role of exercise in the prevention and treatment of compression fractures.

PMID- 17036568
TI  - Trends in the impact factor of scientific journals.

PMID- 17036569
TI  - A brief reply to Carson Strong.
AB  - Carson Strong's reply to my response to his article demonstrates what happens
      when there is unacknowledged disagreement about the facts of a case or about the
      meaning of the terms used to describe those facts. I hope that our dialogue will
      help reduce this disagreement.

PMID- 17036570
TI  - The need for pain control during scaling and root planing.
AB  - Scaling and root planing is a common procedure in clinical practice. Despite the
      frequency of the procedure, the control of pain associated with scaling and root
      planing has not been well studied. Recently, studies have pointed out a need for
      pain control during the procedure in a significant number of subjects-perhaps as
      many as 30% of patients. This need for pain control is similar to the need for
      instrumentation during maintenance therapy. The need also is similar whether hand
      instrumentation or ultrasonic equipment is used. The current most used form of
      pain control is local anesthesia injections. However, many patients object to the
      use of "the needle." Therefore, there is a need for a noninjectable form of pain
      control that is effective.

PMID- 17036571
TI  - Efficacy of an intrapocket anesthetic for scaling and root planing procedures: a
      review of three multicenter studies.
AB  - In recent years, three multicenter studies have been conducted to evaluate the
      clinical efficacy of an active 5% dental gel to reduce pain when placed into
      periodontal pockets before initiating scaling and root planing procedures. In
      each of the clinical studies, the researchers found statistically significant
      differences between the pain scores of the active dental gel group and the
      placebo gel group that favored the active gel for the control of pain during
      periodontal scaling and root planing procedures. This article reviews each of the
      three studies and highlights some of the differences among them.

PMID- 17036572
TI  - Quantification of patient fears regarding dental injections and patient
      perceptions of a local noninjectable anesthetic gel.
AB  - Data have shown that 30% of all Americans do not seek dental care and/or
      treatment unless a problem arises that causes them severe pain. Similar study
      results have been found in Europe as well. While some studies indicate that cost
      concerns prevent people from seeking dental care, the fear of pain has been
      identified as a factor in keeping people from seeing a dentist. A random sample
      of US and European patients who had recently undergone a scaling and root planing
      procedure was surveyed via telephone interview to quantify data on patient
      concerns and fears regarding anesthesia administered by injection, as well as to
      determine patient interest and price perception of an anesthetic gel product. The
      survey also provided data on the patient's experience and perception about the
      scaling and root planing procedure. Responses from the study population showed
      that patients find the injection painful and do not like the prolonged numbness.
      Additionally, based on the patients surveyed, they experience injection anxiety
      before appointments, and a significant number of them cancel appointments or
      simply do not seek treatment because they are afraid of the injection. Finally,
      the study also demonstrated that, while not eliminating dental anxiety
      completely, the availability of a new noninjectable anesthetic would assist in
      relieving patient fear, with almost half of the patients surveyed being more
      likely to seek treatment if only the new noninjectable anesthetic was used.
      Additionally, most patients surveyed would be willing to pay for the
      noninjectable anesthetic out of their own pockets if it was not covered by their
      health insurance.

PMID- 17036573
TI  - Extreme obesity: a new medical crisis in the United States.
AB  - The prevalence of obesity has markedly increased in the past few decades, and
      this disorder is responsible for more health care expenditures than any other
      medical condition. The greater the body mass index (BMI) (calculated as weight in
      kilograms divided by the square of height in meters), the greater the risk of
      comorbidities, including diabetes mellitus, hypertension, obstructive sleep
      apnea, many cancers, dyslipidemia, cardiovascular disease, and overall mortality.
      Class III (extreme) obesity, defined as a BMI of 40 kg/m2 or greater, has also
      increased such that it now affects almost 1 in 20 Americans. The prevalence of
      extreme obesity is greater among women than among men and greater among blacks
      than among non-Hispanic whites or Hispanics. The effect of extreme obesity on
      mortality is greater among young than among older adults, greater among men than
      among women, and greater among whites than among blacks. The current permissive
      environment that promotes increased dietary energy intake and decreased energy
      expenditure through reduced daily physical activity coupled with genetic
      susceptibility is an important pathogenic factor. The number of bariatric
      surgical procedures performed annually is relatively small but increasing.

PMID- 17036574
TI  - Assessment and preparation of patients for bariatric surgery.
AB  - The number of bariatric surgical procedures performed in the United States has
      increased steadily during the past decade. Currently accepted criteria for
      consideration of bariatric surgery include a body mass index (calculated as
      weight in kilograms divided by the square of height in meters) of 40 kg/m2 or
      greater (or >35 kg/m2 with obesity-related comorbidities), documented or high
      probability of failure of nonsurgical weight loss treatments, and assurance that
      the patient is well informed, motivated, and compliant. Appropriate patient
      selection is important in achieving optimal outcomes after bariatric surgery. In
      this article, we review our approach to the medical and psychological assessment
      of patients who want to undergo bariatric surgery. The medical evaluation is
      designed to identify and optimally treat medical comorbidities that may affect
      perioperative risks and long-term outcomes. The psychiatric and psychological
      assessment identifies factors that may influence long-term success in maintaining
      weight loss and prepares the patient for the lifestyle changes needed both before
      and after surgery.

PMID- 17036575
TI  - Surgical approaches to obesity.
AB  - Bariatric surgery has evolved considerably since the introduction of jejunoileal
      bypass in the 1950s. With modifications of early procedures, implementation of
      new techniques, and establishment of minimally invasive approaches, operative
      intervention has become the mainstay in the treatment of extreme (class III)
      obesity. The laparoscopic adjustable gastric band technique is the most common
      purely restrictive procedure. Advantages of the laparoscopic adjustable gastric
      band include reduced perioperative morbidity and mortality compared to other
      bariatric procedures, but this procedure has been associated with substantial
      intermediate and long-term complications. Although vertical banded gastroplasty
      was associated with decreased perioperative morbidity and acceptable early weight
      loss, results from long-term follow-up have been discouraging. Roux-en-Y gastric
      bypass (RYGB) is the most common bariatric procedure performed in the United
      States because of its effectiveness in long-term weight loss and low rates of
      serious complications. Modifications of RYGB to induce malabsorption have led to
      greater weight loss but increased risks of metabolic and nutritional sequelae.
      Duodenal switch is a malabsorptive procedure associated with excellent weight
      loss and resolution of weight-related comorbidities, but concerns regarding
      potential metabolic and nutritional sequelae have limited its widespread use.
      Laparoscopic approaches to bariatric procedures have reduced wound-related
      complications and improved patient recovery. However, the incidence of
      anastomotic leak and internal hernia is higher after laparoscopic RYGB compared
      to the open approach. Each of the currently available bariatric procedures has
      both advantages and disadvantages that must be considered in determining which
      operation should be selected for an individual patient.

PMID- 17036576
TI  - Perioperative care of patients undergoing bariatric surgery.
AB  - The epidemic of obesity in developed countries has resulted in patients with
      extreme (class III) obesity undergoing the full breadth of medical and surgical
      procedures. The popularity of bariatric surgery in the treatment of extreme
      obesity has raised awareness of the unique considerations in the care of this
      patient population. Minimizing the risk of perioperative complications that
      contribute to morbidity and mortality requires input from several clinical
      disciplines and begins with the preoperative assessment of the patient. Airway
      management, intravenous fluid administration, physiologic responses to
      pneumoperitoneum during laparoscopic procedures, and the risk of thrombotic
      complications and peripheral nerve injuries in extremely obese patients are among
      the factors that present special intraoperative challenges that affect
      postoperative recovery of the bariatric patient. Early recognition of
      perioperative complications and education of the patient regarding postoperative
      issues, including nutrition and vitamin supplementation therapy, can improve
      patient outcomes. A suitable physical environment and appropriate nursing and
      dietetic support provide a safe and dignified hospital experience. This article
      reviews the multidisciplinary management of extremely obese patients who undergo
      bariatric surgery at the Mayo Clinic.

PMID- 17036577
TI  - Clinical management after bariatric surgery: value of a multidisciplinary
      approach.
AB  - Comprehensive and collaborative longitudinal care is essential for optimal
      outcomes after bariatric surgery. This approach is important to manage the many
      potential surgical and medical comorbidities in patients who undergo bariatric
      surgery. Medical management programs require prompt and often frequent adjustment
      as the nutritional program changes and as weight loss occurs. Familiarity with
      the recommended nutritional program, monitoring and treatment of potential
      vitamin and mineral deficiencies, effects of weight loss on medical comorbid
      conditions, and common postoperative surgical issues should allow clinicians to
      provide excellent care. Patients must understand the importance of regularly
      scheduled medical follow-up to minimize potentially serious medical and surgical
      complications. Because the long-term success of bariatric surgery relies on
      patients' ability to make sustained lifestyle changes in nutrition and physical
      activity, we highlight the role of these 2 modalities in their overall care. Our
      guidelines are based on clinical studies, when available, combined with our
      extensive clinical experience. We present our multidisciplinary approach to
      postoperative care that is provided after bariatric surgery and that builds on
      our presurgical evaluation.

PMID- 17036578
TI  - Long-term outcome of bariatric surgery: an interim analysis.
AB  - With the increasing number of bariatric surgical procedures being performed,
      outcome assessment is of even greater importance. Few randomized, controlled
      prospective trials have compared bariatric surgery to nonsurgical weight-loss
      treatments, and the quality of current outcome data is suboptimal. However, the
      available evidence suggests that bariatric surgery, and particularly gastric
      bypass, is the most effective weight-loss treatment for people with extreme
      (class III) obesity. In addition to reduced energy intake and to a lesser extent
      malabsorption, numerous other potential mechanisms related to bariatric surgery
      may play a role in promoting weight loss and improving comorbidities. After
      bariatric surgery, clinical improvement or resolution has been reported in 64% to
      100% of patients with diabetes mellitus, 62% to 69% of patients with
      hypertension, 85% of patients with obstructive sleep apnea, 60% to 100% of
      patients with dyslipidemia, and up to 90% of patients with nonalcoholic fatty
      liver disease. A wide range of other weight-related conditions also appear to
      improve, and limited data suggest that overall mortality may decrease in patients
      undergoing bariatric surgery. Although not conclusive, evidence from available
      studies indicates that bariatric surgery is cost-effective. Further research with
      improved methodology is needed to define the mechanisms of action of bariatric
      surgery; to document its effect on long-term weight loss, comorbid conditions,
      and overall mortality; and to determine its cost-effectiveness.

PMID- 17036579
TI  - What price a healthy profession?

PMID- 17036580
TI  - An unavoidable and unmistakable link.

PMID- 17036581
TI  - Controversy is absence of fact.

PMID- 17036582
TI  - Dental assisting law amended to expand duties for certified dental assistants.

PMID- 17036583
TI  - Trends in oral piercing in Buffalo, New York, high schools.
AB  - The purpose of this research was to examine the trend of high school adolescents
      obtaining an oral piercing. A questionnaire was sent to five high schools in
      Buffalo, NY. Of the 508 questionnaires returned, 49 of the respondents (10%) had
      an oral piercing. Post-piercing occurrences included swelling, tenderness,
      numbness, loss of taste, bleeding and pus. Oral piercing maintenance was minimal
      or non-existent. Dental trauma/piercing-related injuries were common. Researchers
      concluded that the oral piercing trend in Buffalo, NY, high schools is small;
      however, students who are getting oral piercings are doing so without parental
      consent and often show signs of infection.

PMID- 17036584
TI  - Use of SIG device to accurately place permanent miniature dental implants to
      retain mandibular overdenture. A case report.
AB  - A case of mini-dental implant insertion for retention of a mandibular overdenture
      in a hospitalized patient has been documented. The additional use of the SIG
      (drill guide) directional device in the implant placement protocol gave the
      practitioner more confidence and resulted in the proper alignment of the three
      ball-top, one-piece fixtures. The three implants were inserted exactly 1 cm apart
      and parallel to each other. The distal fixtures were approximately 1 cm away from
      the mental foramina, thereby eliminating the risk of lip paresthesia. Keeper caps
      were placed in the denture's intaglio after one month. The keeper caps allowed
      for proper retention of the overdenture. The caps also enabled the patient to
      easily insert and withdraw his denture, even though he displayed limited manual
      dexterity. The tissue response was excellent, and oral hygiene was made easier
      with adequate spacing of the exposed ball-tops. The overall experience for both
      the operator and the patient was very positive. General dentists should be able
      to readily master this technique and add it to their armamentarium for the
      benefit of all their patients.

PMID- 17036585
TI  - Surgical management of iatrogenic root perforation following endodontic therapy.
AB  - Endodontic mishaps still occur despite technological advancements in the field of
      dental instrumentation and materials. Iatrogenic root perforations during access
      preparation, canal instrumentation or preparation of post space are not uncommon,
      and instrument fractures during filing or reaming, as well as root fractures
      during condensation, are also encountered. Many of these mishaps are hard to
      avoid because of the extreme variability in root canal anatomy, canal
      calcification, abnormal root shapes and curvatures. They occur most often during
      access preparation, root cleaning, shaping and preparation of post space, or when
      attempting to bypass fractured instruments. Procedural errors impede endodontic
      therapy, thus increasing the risk of treatment failure, especially in teeth with
      necrotic pulps and periradicular lesions. Clinicians often have difficulty
      diagnosing and treating root perforations and the treatment of such mishaps is
      very difficult, especially in posterior teeth and in the area of the mandibular
      furcation. We report on a case of root perforation in a mandibular first molar
      that was successfully treated by surgery without the use of additional
      biomaterials.

PMID- 17036586
TI  - Diagnosis and clinical significance of dens invaginatus to practicing dentist.
AB  - Dens invaginatus, commonly known as dens in dente, is a developmental
      malformation of teeth that most commonly affects permanent maxillary lateral
      incisors. Deciduous teeth are infrequently affected. Presence of dens invaginatus
      in mandibular permanent teeth is extremely uncommon. A rare presentation of
      coronal double dens invaginatus incidentally detected in a mandibular canine
      tooth on radiographic examination is being reported, along with a discussion of
      this anomaly. The patient had presented for routine dental treatment unrelated to
      this finding. In addition, the various radiographic appearances of dens
      invaginatus, as they present within the maxillary and mandibular teeth, are
      described. Essential clinical considerations and treatment options are presented.
      A review of the pertinent literature is undertaken, and tables summarizing
      previously published reports of mandibular dens invaginatus and double dens
      invaginatus are presented. A review of the literature indicates that dens
      invaginatus in mandibular teeth is extremely rare, with only 11 other cases,
      involving 14 teeth, reported previously. Cases of double dens invaginatus are
      even more atypical, with only eight previously reported cases. Dens invaginatus
      is an anomaly that should be familiar to all practicing dentists because of the
      clinical implications and potential sequelae.

PMID- 17036587
TI  - Find canals faster through basic research.
AB  - Achieving access and finding canals are the key first steps in the endodontic
      procedure. This has always been a time-consuming, qualitative procedure that
      relies on the dentist's experience and feel. Recent basic research has been
      published that shows that the anatomic morphological measurements concerning the
      pulp chamber are very consistent in every tooth. This research points the way to
      a quantitative, predictable and quick technique for making endodontic access
      preparations without risk. The research and clinical technique are described in
      this article.

PMID- 17036588
TI  - Stabilization of endotracheal tube--a technical note.
AB  - The vital need to retain closed-circuit airways during maxillofacial surgery has
      led to several innovations in anesthetic tube placement and stabilization.
      Several designs and alterations of endotracheal tubes have been described and are
      currently in use. These range from suturing the tubing to the patient's scalp to
      fabricating maxillofacial prostheses. In this report, an easy method for securing
      anesthetic tubes is described. This technique has been used successfully at our
      institution.

PMID- 17036589
TI  - Cystic hygroma.
AB  - Cystic hygroma (CH) is a benign, developmental condition of unknown etiology. 90%
      of the cases are present by age 2. CH represents malformed lymphatics that fail
      to communicate with larger veins and, therefore, they collect lymph. It is a type
      of lymphangioma. The clinical presentation is one of a painless, soft mass that
      reaches a giant size and can lead to the death of the infant. The diagnosis is
      done with CT scan and biopsy. We report a severe case of CH and describe the
      difficult surgical treatment, despite the benign nature of the lesion.

PMID- 17036590
TI  - Survey of sedation techniques used Among pediatric dentists in New York State.
AB  - The purpose of this study was to evaluate pediatric dentists in New York State
      who use oral sedation. Results indicated that fewer than 50% of pediatric
      dentists used oral sedatives in their office, but that of these dentists, more
      than 50% reported that their sedations are successful.

PMID- 17036591
TI  - Highlighting nurses' contribution to patient care: Examining nurse-sensitive
      outcomes.

PMID- 17036592
TI  - Oncology nursing: Finding the balance in a changing health care system.
AB  - Health care restructuring has resulted in significant changes in the workload and
      work environment for oncology nurses. While recent studies describe the impact of
      these changes on the general nursing workforce in several countries, there have
      been no published studies that have focused on worklife issues of Canadian
      oncology nurses. Therefore, a qualitative study was conducted to gain insight
      about how oncology nursing has changed over the past decade and how Canadian
      oncology nurses are managing these changes. Analysis of telephone interviews with
      51 practising oncology nurses employed across Canada revealed three major themes.
      The first theme, "health care milieu", portrayed a picture of the cancer care
      environment and patient and professional changes that occurred over the past
      decade. The second theme, "conflicting demands", reflects how the elements of
      change and social forces have challenged professional oncology nursing practice.
      The third theme, "finding the way", describes the patterns of behaviour that
      nurses used to manage the changing health care environment and make meaning out
      of nurses' work in cancer care. Overall, the findings portray a picture of
      Canadian oncology nurses in "survival mode". They face many workplace challenges,
      but are able to keep going "for now" because they find ways to balance their
      responsibilities on a daily basis and because they know and believe that their
      specialized nursing knowledge and skills make a difference in patient care.

PMID- 17036593
TI  - Redefining the primary nurse role in oncology care: A 21st century perspective.
AB  - Oncology nursing is a rapidly evolving specialty with increasing demands upon
      nurses to respond to the complex needs of cancer patients and their families.
      Primary nursing (PN) has been the model of care delivery utilized at our cancer
      centre for more than two decades. The nursing department determined it was time
      that a review and redefining of the role be undertaken. These objectives were
      achieved through the implementation of the Primary Nurse Role Development
      Project. This article discusses: a brief background of why the existing role
      needed to be reviewed and revised; an overview of how primary nursing has been
      applied historically at the centre; and details regarding the project plan and
      its implementation. Results from the project provided a competency-based oncology
      primary nurse role description, which will be outlined along with proposals for
      improving nursing practice. Our goal is to achieve optimal care for our patients.

PMID- 17036594
TI  - Caring for the caregivers: Innovative program for oncology nurses.
AB  - An innovative program, Care for the Professional Caregiver, was designed to
      provide staff nurses in a cancer program with the opportunity to learn about
      coping with stress in their practice. The program was evaluated using
      quantitative and qualitative methods. The findings clearly describe the benefits
      of the program on both a short- and long-term basis. The value of connecting with
      other cancer nurses, supporting each other, and sharing stories about their work
      life experiences resulted in benefits to the nurse as an individual, as a team
      member, and as a professional practitioner. The program achieved its aims and is
      recommended for ongoing implementation.

PMID- 17036595
TI  - Not "simply" teaching another chemotherapy patient...

PMID- 17036596
TI  - Preventive medicine in Task Force 1st Armored Division during Operation Iraqi
      Freedom.
AB  - Task Force 1st Armored Division (TF1AD) deployed to Baghdad and South Central
      Iraq from April 2003 through July 2004. TF1AD preventive medicine had
      responsibility for ensuring divisional force health protection, including soldier
      health, disease and nonbattle injury mitigation, health promotion, and civil
      affairs operations. Heat injury, diarrheal disease, skin and respiratory disease,
      and eye and musculoskeletal injury rates were high. Command emphasis and
      preventive medicine action resulted in better living conditions and personal
      sanitation. To counter the threat, the TF1AD preventive medicine/ division
      surgeon team used a "spiraling out" approach that focused attention first on hand
      washing, potable water, vector control, waste disposal, and food sanitation and
      later on noise, asbestos, environmental contamination, and radiation. In April
      2004, TF1AD shifted focus to the Multinational Division Central-South region of
      Iraq and many similar problems occurred as in May 2003, although they were less
      severe, in part because of the lessons learned in Baghdad.

PMID- 17036597
TI  - Noninvasive hemodynamic monitoring for combat casualties.
AB  - The aims of this study were to develop and to test a noninvasive hemodynamic
      monitoring system that could be applied to combat casualties to supplement
      conventional vital signs, to use an advanced information system to predict
      outcomes, and to evaluate the relative effectiveness of various therapies with
      instant feedback information during acute emergency conditions. In a university
      run inner city public hospital, we evaluated 1,000 consecutively monitored trauma
      patients in the initial resuscitation period, beginning shortly after admission
      to the emergency department. In addition to conventional vital signs, we used
      noninvasive monitoring devices (cardiac index by bioimpedance with blood pressure
      and heart rate to measure cardiac function, arterial hemoglobin oxygen saturation
      by pulse oximetry to reflect changes in pulmonary function, and tissue
      oxygenation by transcutaneous oxygen tension indexed to fractional inspired
      oxygen concentration and carbon dioxide tension to evaluate tissue perfusion).
      The cardiac index, mean arterial pressure, pulse oximetry (arterial hemoglobin
      oxygen saturation), and transcutaneous oxygen tension/fractional inspired oxygen
      concentration were significantly higher in survivors, whereas the heart rate and
      carbon dioxide tension were higher in nonsurvivors. The calculated survival
      probability was a useful outcome predictor that also served as a measure of
      severity of illness. The rate of misclassification of survival probability was
      13.5% in the series as a whole but only 6% for patients without severe head
      injuries and brain death. Application of noninvasive hemodynamic monitoring to
      acute emergency trauma patients in the emergency department is feasible, safe,
      and inexpensive and provides accurate hemodynamic patterns in continuous, on
      line, real-time, graphical displays of the status of cardiac, pulmonary, and
      tissue perfusion functions. Combined with an information system, this approach
      provided an early outcome predictor and evaluated, with an objective
      individualized method, the relative efficacy of alternative therapies for
      specific patients.

PMID- 17036598
TI  - Bacteria recovered from patients admitted to a deployed U.S. military hospital in
      Baghdad, Iraq.
AB  - The predominant bacteria and antimicrobial susceptibilities were surveyed from a
      deployed, military, tertiary care facility in Baghdad, Iraq, serving U.S. troops,
      coalition forces, and Iraqis, from August 2003 through July 2004. We included
      cultures of blood, wounds, sputum, and urine, for a total of 908 cultures; 176 of
      these were obtained from U.S. troops. The bacteria most commonly isolated from
      U.S. troops were coagulase-negative staphylococci, accounting for 34% of
      isolates, Staphylococcus aureus (26%), and streptococcal species (11%). The 732
      cultures obtained from the predominantly Iraqi population were Klebsiella
      pneumoniae (13%), Acinetobacter baumannii (11%), and Pseudomonas aeruginosa
      (10%); coagulase-negative staphylococci represented 21% of these isolates. These
      differences in prevalence were all statistically significant, when compared in
      chi2 analyses (p < 0.05). Antimicrobial susceptibility testing demonstrated broad
      resistance among the Gram-negative and Gram-positive bacteria.

PMID- 17036599
TI  - Bacteriology of war wounds at the time of injury.
AB  - Bacterial contamination of war wounds occurs either at the time of injury or
      during the course of therapy. Characterization of the bacteria recovered at the
      time of initial trauma could influence the selection of empiric antimicrobial
      agents used to prevent infection. In the spring of 2004, U.S. military casualties
      who presented to the 31st Combat Support Hospital in Baghdad, Iraq, with acute
      traumatic injuries resulting in open wounds underwent aerobic culture of their
      wounds to identify the bacteria colonizing the wounds. Forty-nine casualties with
      61 separate wounds were evaluated. Wounds were located predominantly in the upper
      and lower extremities and were primarily from improvised explosive devices or
      mortars. Thirty wounds (49%) had bacteria recovered on culture, with 40 bacteria
      identified. Eighteen casualties (20 wounds) had undergone field medical therapy
      (irrigation and/or antimicrobial treatment); six of these had nine bacterial
      isolates on culture. Of the 41 wounds from 31 patients who had received no
      previous therapy, 24 grew 31 bacteria. Gram-positive bacteria (93%), mostly skin
      commensal bacteria, were the predominant organisms identified. Only three Gram
      negative bacteria were detected, none of which were characterized as broadly
      resistant to antimicrobial agents. The only resistant bacteria recovered were two
      isolates of methicillin-resistant Staphylococcus aureus (MRSA). Our assessment of
      war wound bacterioly soon after injury reveals a predominance of Gram-positive
      organisms of low virulence and pathogenicity. The presence of MRSA in wounds
      likely reflects the increasing incidence of community-acquired MRSA bacteria.
      These data suggest that the use of broad-spectrum antibiotics with efficacy
      against more resistant, Gram-negative bacteria, such as Pseudomonas aeruginosa
      and Acinetobacter spp., is unnecessary in early wound management.

PMID- 17036600
TI  - Skin lesions in barracks: consider community-acquired methicillin-resistant
      Staphylococcus aureus infection instead of spider bites.
AB  - Recent outbreaks of mysterious skin lesions on multiple personnel at several
      military facilities were initially blamed on spiders. Requests were made for pest
      inspection and control to remedy the situation. Greater scrutiny of the situation
      led to a hypothesis that instead of spiders, an infectious outbreak of community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) should be
      investigated as the etiology. Subsequent culturing of the lesions on personnel at
      one facility confirmed this bacterial etiology. Barracks, as well as other close
      quarter military living conditions, are ripe environments for the establishment,
      persistence, and spread of CA-MRSA. Military medical personnel should consider CA
      MRSA as a more likely etiologic agent than spider bites for cutaneous eruptions
      in which there are multiple lesions on one person or multiple patients with
      similar lesions.

PMID- 17036601
TI  - Acanthamoeba keratitis in a U.S. Army soldier after unauthorized use of contact
      lenses in the combat theater.
AB  - A 25-year-old active duty Army E-5 developed severe infectious keratitis in his
      left eye secondary to soft contact lens (CL) wear while deployed in Iraq,
      necessitating evacuation to Walter Reed Army Medical Center for further
      evaluation and treatment. Initial clinical examination at Walter Reed Army
      Medical Center was suggestive of Acanthamoeba keratitis, a serious corneal
      pathogen associated with CL wear. In vivo confocal microscopy demonstrated
      Acanthamoeba cysts in the epithelium and anterior stroma, and smears and cultures
      from an epithelial biopsy specimen confirmed the diagnosis of Acanthamoeba
      keratitis. To our knowledge this is the first reported case of Acanthamoeba
      keratitis in a soldier wearing CLs in the combat theater. Because of the
      inability to maintain proper lens hygiene in a combat or field environment, the
      risk of developing a potentially sight-threatening corneal infection is
      significant. This unfortunate case of a devastating eye infection serves as a
      reminder of the current Army policy, which prohibits the use of CLs during gas
      chamber exercises, field training, and combat.

PMID- 17036602
TI  - Transvaginal hysterectomy for enlarged leiomyomata uteri in a Medical Department
      Activity environment.
AB  - During a 6-year period, 119 patients with enlarged leiomyomata uteri underwent a
      transvaginal hysterectomy at this medium-size Medical Department Activity using
      morcellation to debulk the uterus. One hundred seventeen underwent successful
      removal of the uterus with the use of various morcellation techniques to reduce
      the uterine size. Two patients required conversion to an abdominal procedure. A
      retrospective review of each operative report was completed, and the findings are
      presented in this study. There was a low morbidity rate in this series, with no
      deaths. Transvaginal hysterectomy with debulking of enlarged leiomyomata using
      morcellation is a safe alternative to abdominal hysterectomy in a Medical
      Department Activity environment.

PMID- 17036603
TI  - Pelvic pain presenting in a combat environment.
AB  - OBJECTIVE: The objective was to identify the incidence of pain disorders in the
      deployed female active duty population in support of Operation Iraqi Freedom.
      METHODS: Retrospective chart review was completed on all patients who were seen
      for gynecologic services at Camp Doha, Kuwait, from September 2003 through March
      2004. One thousand seven hundred thirty-seven patients were identified.
      Statistical analysis was performed. RESULTS: Of the 1,737 patients seen during
      the study period, 150 patients were identified as having a pelvic pain disorder.
      These patients accounted for 14% of all patients seen for gynecologic services.
      Mean age was 28 +/- 8 years (range, 15-53 years). Pelvic pain of unclear etiology
      and cystitis were the most common diagnoses made accounting for 19% and 16% of
      encounters. CONCLUSIONS: Acute pelvic pain disorders can be effectively managed
      in the combat environment. Optimization of predeployment regimens for management
      of pain is strongly recommended. Consideration should be given to making soldiers
      with chronic pelvic pain disorders that fail to respond to predeployment medical
      management nondeployable.

PMID- 17036604
TI  - Suicide and the air force mental health provider: frequency and impact.
AB  - Although suicide is relatively common among mental health patients, few studies
      have been published detailing the effects of a patient's suicide on his or her
      mental health provider. We reviewed data from 97 active duty, Air Force, mental
      health providers who responded to an anonymous survey. Forty-eight percent of the
      providers had experienced a patient's suicide. One-third of them reported a sense
      of responsibility for that patient's death. More than 20% reported significant
      emotional or behavioral changes following the death. Many providers experienced
      alterations in their self-esteem and their use of peer consultation following the
      suicide. Speaking to clergy members, friends, and other providers was generally
      beneficial following the suicide of a patient. Recommendations are given to
      minimize the impact of this tragedy on providers.

PMID- 17036605
TI  - Stress, mental health, and job performance among active duty military personnel:
      findings from the 2002 Department of Defense Health-Related Behaviors Survey.
AB  - This study examined the extent to which high levels of occupational and family
      stress were associated with mental health problems and productivity loss among
      active duty military personnel. We analyzed data from the 2002 Department of
      Defense Survey of Health-Related Behaviors among Military Personnel, which
      provided extensive population-based information on 12,756 active duty personnel
      in all branches of the military worldwide. Military personnel reported higher
      levels of stress at work than in their family life. The personnel reporting the
      highest levels of occupational stress were those 25 or younger, those who were
      married with spouses not present, and women. Personnel with high levels of stress
      had significantly higher rates of mental health problems and productivity loss
      than those with less stress. We recommend that prevention and intervention
      efforts geared toward personnel reporting the highest levels of stress be given
      priority for resources in this population.

PMID- 17036606
TI  - The Trauma Symptom Inventory: factors associated with invalid profiles in a
      sample of combat veterans with post-traumatic stress disorder.
AB  - The assessment of combat-related post-traumatic stress disorder (PTSD) relies
      upon self-reported symptoms and the need for indicators of valid reporting is
      critical. The Trauma Symptom Inventory (TSI) is a testing instrument specific to
      PTSD which includes validity scales. In a pilot study examining the use of the
      TSI with combat veterans, 50 male veterans diagnosed with PTSD were administered
      the TSI. Nineteen percent of the profiles were invalid, all but one based on the
      Atypical Response Scale. Differences between veterans with valid and invalid TSI
      profiles are examined in terms of demographic and historical factors, TSI
      profiles, and individual scale items. The model best able to predict invalid
      profiles included high scores on subscales measuring dissociative experiences and
      tension reduction behaviors. Implications for the interpretation of TSI validity
      scales in assessing combat-related PTSD are discussed.

PMID- 17036608
TI  - High prevalence of iron deficiency and anemia in female military recruits.
AB  - Iron deficiency anemia has long been known to impair physical and mental
      performance. Iron deficiency itself, even without anemia, may also cause such an
      effect. Similar to female athletes, women in active military units may have
      increased risks for iron deficiency and its detrimental effects. Female recruits
      were screened for anemia and iron store status, and a questionnaire on lifestyle
      habits and menstruation was completed. Iron depletion (serum ferritin level of
      <20 microg/L) was found for 77% of study participants. Iron deficiency (ferritin
      level of <12 microg/L and transferrin saturation of <15%) was found for 15% of
      study participants. Anemia was found for 24% of subjects, and iron deficiency
      anemia was found for 10% of subjects. High prevalence of iron depletion, iron
      deficiency, anemia, and iron deficiency anemia was found among female recruits
      intended for active military duty. Therefore, a recommendation can be made to
      screen such female recruits for anemia and iron stores.

PMID- 17036607
TI  - Job stress, depression, work performance, and perceptions of supervisors in
      military personnel.
AB  - OBJECTIVE: Recent studies have identified high levels of job stress in military
      personnel. This study examined the relationship among job stress, depression,
      work performance, types of stressors, and perceptions about supervisors in
      military personnel. METHODS: Eight hundred nine military personnel answered a 43
      item survey on work stress, physical and emotional health, work performance,
      perceptions about leadership, job stressors, and demographics. RESULTS: More than
      one- quarter (27.4%) of this military population reported suffering from
      significant job stress. Both the report of work stress and depression were
      significantly related to impaired work performance, more days of missed work,
      poorer physical health, and negative perceptions about the abilities of
      supervisors and commanders. Depression and job stress were significantly and
      positively related to each other. CONCLUSIONS: These results support accumulating
      data indicating that work stress is a significant occupational health hazard in
      the routine military work environment. Targeting and eliminating sources of job
      stress should be a priority for the U.S. military to preserve and protect the
      mental health of military personnel.

PMID- 17036609
TI  - Predictors of aversive alcohol consequences in a military sample.
AB  - The purpose of this study was to identify predictors of risky alcohol use and
      alcohol-related consequences among postdeployment soldiers. Demobilizing soldiers
      completed an assessment packet that included questions about demographic factors,
      relationships, stress, and alcohol-related consequences. Significant predictors
      of greater alcohol-related consequences, as assessed with the CAGE questionnaire,
      included fewer years of formal education, male gender, not being in an intimate
      relationship, racial/ethnic minority status, enlisted rank, having been deployed
      to the continental United States, and greater stress, whereas significant
      predictors of drinking and driving included male gender, not being in an intimate
      relationship, and greater stress. Identifying the predictors of alcohol
      consequences that occur upon demobilization may aid in determining which soldiers
      are at risk for such consequences before deployment and may help to maintain
      military readiness.

PMID- 17036610
TI  - Surgical nurse practitioners as registered nurse first assists: the role,
      historical perspectives, and educational training.
AB  - Advanced practice nurses (APN) who practice in the surgical subspecialty areas
      may have the opportunity to expand their scope of practice to include first
      assistant at surgery. Surgical APNs who practice as registered nurse first
      assistants (RNFA) should seek credentialing and apply for institutional
      privileges to assure the consumer of competent providers. Credentialing as an
      RNFA documents the educational learning process and skills acquired, and
      recognizes this area of expertise. The role of the APN as an RNFA at surgery is
      practiced within the specialty area of perioperative nursing which includes
      preoperative, intraoperative, and postoperative care. In this study, the nurse
      practitioners describe the role of the RNFA, its historical evolution over
      wartime, the required educational training, and the benefits of the role for
      patient care. The surgical nurse practitioner who undertakes training and
      education as a surgical RNFA is in an excellent position to provide patient care
      across the surgical continuum.

PMID- 17036611
TI  - Reliability and validity testing of a short form of the Readiness Estimate and
      Deployability Index Revised for Air Force Nurses.
AB  - OBJECTIVE: The purpose of this study was to test the reliability and validity of
      the Readiness Estimate and Deployability Index Revised for Air Force Nurses Short
      Form, with a sample of 205 Air Force nurses. Participants were mostly female
      (70%), 36.31 +/- 9.3 years of age, with 11.52 +/- 7.17 years of nursing
      experience. METHODS: With structural equation modeling, the initial model did not
      fit the data (chi2/df = 5.45) and was revised. RESULTS: Revisions based on
      modification indices provided evidence of reliability (alpha coefficients of 0.70
      0.94; the majority of R2 values were >0.50) and improved the fit of the model
      (chi2 difference, 35.54; df difference, 3.76; p < 0.05). Hypothesis testing
      provided evidence of construct validity. CONCLUSIONS: The 40-item Readiness
      Estimate and Deployability Index Revised for Air Force Nurses Short Form provides
      evidence of reliability and validity as a self-assessment measure of deployment
      preparedness.

PMID- 17036612
TI  - Humanitarian assistance medicine: perceptions of preparedness: a survey-based
      needs assessment of recent U.S. Army internal medicine residency graduates.
AB  - The U.S. military provides humanitarian assistance in many areas around the
      globe. With recent changes in the force structure of the U.S. Army, internal
      medicine physicians are now at the forefront of providing this care, but the
      extent of their involvement is not known. This study measured the frequency with
      which recently trained Army internists provided humanitarian assistance, and it
      assessed their perceived preparedness for such missions. All graduates from Army
      internal medicine programs for 4 consecutive years were invited by e-mail to
      participate in an Internet-based survey. Eighty-nine personnel (49% of those
      contacted) completed the survey. Of those in a deployable position for >6 months,
      72% provided medical humanitarian assistance. Most thought that additional
      training was needed, especially in tropical disease management, sanitation, and
      the practices of civilian humanitarian workers. This study demonstrates that
      military-trained internists are frequently involved in humanitarian assistance
      medicine, and it suggests that they might benefit from additional training.

PMID- 17036613
TI  - Humanitarian assistance in Afghanistan: a prospective evaluation of clinical
      effectiveness.
AB  - OBJECTIVE: To examine the clinical effectiveness of patient encounters during
      humanitarian assistance (HA) missions performed by the 48th Combat Support
      Hospital in Afghanistan. METHODS: Data were prospectively gathered from missions
      in the villages of Aroki (January 21, 2003), Tangee (March 25, 2003), and Turkman
      (April 22, 2003). Health care providers evaluated the effectiveness of each
      patient encounter using a data-gathering instrument with clearly defined outcome
      measures. RESULTS: A total of 1,887 patients were seen during the three missions.
      Forms were incomplete for 112 patients and not used for 33 dental patients. For
      the remaining 1,742 individuals, probable cures were achieved as follows: adult
      males, 31%; adult females, 52%; male children, 46%; and female children, 54% (all
      patients, 46%, p < 0.001). After adjusting for acute care that was supportive in
      nature during the final mission, probable cures were achieved as follows: adult
      males, 22%; adult females, 16%; male children, 34%; and female children, 27%.
      During this final operation, 73% (p < 0.001) of patients received care that was
      unnecessary, unlikely to produce a cure, or was merely supportive in nature.
      CONCLUSIONS: During HA missions performed by the 48th Combat Support Hospital,
      the majority of patient encounters did not result in curative treatments. The
      effectiveness of medical care during HA missions cannot be assumed and future
      operations should include assessments of outcomes to optimize their value.

PMID- 17036614
TI  - Creation of an innovative laser incident reporting form for improved trend
      analysis using the Delphi technique.
AB  - With expanding numbers of laser applications, there is greater potential for
      laser radiation exposures. Proper surveillance and evaluation of laser incidents
      can lead to better injury prevention and more efficient medical treatment.
      Current laser incident databases do not provide sufficient information for
      surveillance and analysis of laser trends. A laser incident reporting form (LIRF)
      was created for U.S. Air Force applications by using the Delphi technique. To
      create the LIRF, four expert panels were formed by 40 health and safety
      professionals experienced with laser systems and medical evaluation of laser
      incidents. After three rounds of surveys, the final LIRF contained 100 data
      collection fields identifying the most valuable items for injury trend analysis.
      Although the LIRF was initially developed to collect USAF laser incident
      information, it could potentially act as the cornerstone for a new system serving
      the entire military system.

PMID- 17036615
TI  - Assessing the validity of the Stages of Change Readiness and Treatment Eagerness
      Scale with treatment-seeking military service members.
AB  - The purpose of this project was to assess the concurrent and predictive validity
      of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) for
      military service members undergoing substance abuse treatment. Concurrent
      validity was assessed by examining the correlation of SOCRATES subscales with
      subscales from the Addiction Treatment Attitude Questionnaire. Predictive
      validity was assessed by examining the ability of SOCRATES subscales to predict
      length of stay in treatment and successful completion of treatment. Scores on the
      SOCRATES were correlated in the expected direction with scores on the Addiction
      Treatment Attitude Questionnaire and predicted length of stay in treatment and
      successful completion of treatment. The findings provide support for the validity
      of the SOCRATES with substance abuse treatment-seeking military service members.

PMID- 17036616
TI  - Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army
      personnel.
AB  - The U.S. Army recently mandated that soldiers undergo glucose-6-phosphate
      dehydrogenase (G6PD) testing before deployment to malarious regions. We
      retrospectively characterize the presence and degree of G6PD deficiency in U.S.
      military personnel by sex, self-reported ethnicity, and World Health Organization
      deficiency classification through test results obtained October 1, 2004 through
      January 17, 2005. Data were available for 63,302 (54,874 males and 8,428 females)
      subjects; 2.5% of males and 1.6% of females were deficient, with most having only
      moderate enzyme deficiency. African American males (12.2%) and females (4.1%),
      along with Asian males (4.3%), had the highest rates of G6PD deficiency. Most
      males were found to have class III variants while most females were class IV
      variants. The most severely deficient were Asian males (class II). These results
      suggest that universal screening for G6PD deficiency is clinically warranted, and
      particularly essential for those male service members who self-report ethnicity
      as African American, Asian, or Hispanic.

PMID- 17036617
TI  - Use of a centrifuge-based automated blood cell counter for radiation dose
      assessment.
AB  - Hematological changes create early-response biomarkers for assessing radiation
      doses. Existing dose-prediction models are based on serial blood lymphocyte
      counts after acute whole-body exposure to gamma-radiation. Measurements of
      lymphocyte-depletion kinetics after possible exposures are useful for triaging
      patients and managing medical resources. The small-footprint QBC Autoread Plus
      System provides cost-effective hematological analyses with reproducibility,
      accuracy, and a broad dynamic range. QBC analysis measures centrifugally packed,
      whole blood cells in microhematocrit tubes and reports pooled lymphocyte and
      monocyte counts. Our objective was to modify this procedure to report pure
      lymphocyte counts for radiation biodosimetry applications. The CD14 antigen is
      strongly expressed on most human monocytes. Using anti-CD14-coated Dynabeads, we
      have devised a rapid method for depleting monocytes from whole blood without
      altering the lymphocyte viability or count. This simple dry procedure provides
      reliable lymphocyte counts for results that fall within the normal lymphocyte
      count range (1-4 x 10(9) cells per L) for radiation exposure assessment using
      lymphocyte-depletion kinetics.

PMID- 17036618
TI  - Dolasetron versus ondansetron as single-agent prophylaxis for patients at
      increased risk for postoperative nausea and vomiting: a prospective, double
      blind, randomized trial.
AB  - This study identified 100 ambulatory surgery patients receiving general
      anesthesia who were at increased risk for postoperative nausea and vomiting
      (PONV) and randomly assigned them to receive single-agent prophylaxis (12.5 mg of
      dolasetron or 4 mg of ondansetron) 15 to 30 minutes before the end of surgery.
      Data were collected in the postanesthesia care unit, and patients completed a
      questionnaire 24 hours after surgery. No statistically significant difference
      existed between study groups in demographic features, history of PONV, history of
      motion sickness, or type and duration of surgery and anesthesia. No statistically
      significant difference existed in satisfaction with the medication used for PONV
      prophylaxis (dolasetron, 70.9 of 100 mm; ondansetron, 67.9 of 100 mm; p = 0.69).
      No statistically significant difference existed in satisfaction with the overall
      surgical experience (dolasetron, 87.9 of 100 mm; ondansetron, 85.3 of 100 mm; p =
      0.36). Costminimization strategies should be considered without fear of
      substandard care or increased patient dissatisfaction.

PMID- 17036619
TI  - Predictors of exercise compliance in individuals with Gulf War veterans
      illnesses: Department of Veterans Affairs Cooperative Study 470.
AB  - Although the health benefits of exercise for individuals with Persian Gulf War
      veterans illnesses (GWVI) are documented, many of these individuals do not
      exercise regularly enough to obtain benefits. The purpose of this study was to
      investigate factors predicting exercise compliance among individuals with GWVI in
      a multicenter, randomized, clinical trial. Participants were 1,092 veterans who
      reported at least two of the following cardinal symptoms of GWVI: (1) fatigue,
      (2) musculoskeletal pain, and (3) cognitive problems. Participants received
      exercise alone or exercise and cognitive-behavioral therapy. The overall level of
      compliance was relatively low during the exercise treatment phase (46.2%) and
      decreased by one-half during the follow-up period (23.0%). Predictors of
      compliance during treatment included less pain and greater age, motivation, and
      body mass index. Predictors of compliance during the follow-up period included
      less pain and greater age. The results highlight factors that affect adoption and
      maintenance of physical activity in a population with GWVI.

PMID- 17036620
TI  - Radiology corner. Answer to last month's radiology case and image: left atrial
      myxoma.

PMID- 17036621
TI  - How independent are those independent studies?

PMID- 17036622
TI  - It doesn't have to be this way.

PMID- 17036623
TI  - Politically connected.

PMID- 17036624
TI  - When the levees broke.

PMID- 17036625
TI  - This...or that?

PMID- 17036626
TI  - Referrals are good business.

PMID- 17036627
TI  - Your Health. Fat and fast food.

PMID- 17036628
TI  - Why floss?

PMID- 17036629
TI  - You've come a long way, Navy.

PMID- 17036630
TI  - Practice what you preach.

PMID- 17036631
TI  - Lymphodynamics in the fetus and newborn.
AB  - Body fluid is distributed among three major fluid spaces: plasma, interstitial
      fluid, and intracellular fluid. The distribution of fluid in each of these
      compartments is dramatically different in the fetus and newborn compared to the
      adult. In addition, the amniotic fluid that surrounds the fetus may also be
      considered an extension of the extracellular space of the fetus. The purpose of
      this review is to discuss the complex mechanism that regulates volume in the
      fetus and newborn as well as the regulation of fluid distribution between the
      plasma and interstitial fluid, while placing special emphasis on the role the
      lymphatic system plays in mediating and maintaining this distribution.

PMID- 17036632
TI  - Demonstration of tissue alterations by ultrasonography, magnetic resonance
      imaging and spectroscopy, and histology in breast cancer patients without
      lymphedema after axillary node dissection.
AB  - Estimates of the incidence of arm swelling after axillary lymph node dissection
      for breast cancer range from 10 to 37%. Yet the subjective sensation of edema is
      described in at least 54% of patients. The purpose of this research was to
      examine the structural changes occurring in the subcutaneous tissue that might
      explain these subjective complaints using multiple imaging modalities. Two female
      cadavers with unilateral breast amputation and axillary dissection were studied.
      The dermal and subcutaneous layers of both arms were visualized with high
      frequency ultrasonography, and magnetic resonance imaging and spectroscopy (MRS),
      and tissue biopsies were taken for histological evaluation. On the operated side,
      ultrasound imaging showed a hyperechogenic subcutis and the fat-to-water
      relationship in adipose cells was higher as measured by MRS. Dissection of the
      arms revealed structural adipose tissue changes, which were confirmed by
      microscopic evaluation.

PMID- 17036633
TI  - Lymphatic clearance of the human skin in patients with acute deep vein thrombosis
      using a novel fluorescent technique.
AB  - The purpose of this study was to investigate lymphatic clearance of the human
      skin in patients with acute deep thrombosis of the femoral vein. In 13 patients
      with deep vein thrombosis and no other cause for swelling of the limbs, lymphatic
      clearance of the skin at the foot was measured. Ten microliters of fluorescein
      isothiocyanatedextran 150,000 were injected intradermally and the fluorescent
      light intensity of the deposit measured 10 min and 24 hours after injection by
      window densitometry. In addition, intralymphatic pressure was measured by the
      servo-nulling system. The results were compared with a sex- and age-matched
      control group. Fluorescent light intensity decreased by 23.8 +/- 12.3 arbitrary
      units or by a factor of 1.8 +/- 0.5 in patients with DVT after 24 hours, which
      was significantly less than in healthy controls (33.7 +/- 8.9 arbitrary units or
      by factor 5.0 +/- 4.1, p < 0.013). Intralymphatic pressure was not different
      between the two groups. These results indicate that lymphatic clearance is
      significantly reduced in the acute phase of deep venous thrombosis.

PMID- 17036634
TI  - Biomechanical evaluation of scapular girdle in patients with chronic arm
      lymphedema.
AB  - The presence of arm lymphedema can induce alterations in motor functions and
      posture. Using an optoelectronic system (ELITE 2002), we evaluated these
      alterations during a set of tests involving walking, resting and fatigue. The
      results of our biomechanical analysis demonstrated a limited range of motion of
      the affected arm, particularly a reduction in swinging during walking tests, and
      in shoulder retroposition and abduction movements for all patients. After
      repeated cyclical movements, premature fatigue appeared in the pathological arm.
      Lymphedema does not appear to cause alterations to the posture of the spine in
      our study, but drooping of the shoulder homolateral to the lymphedema can occur.
      This kind of investigation, which is quick, easy, and comfortable for patients
      with lymphedema, can be a useful method to evaluate functional capacity, thus
      allowing a quantitative assessment of the loss of function and the optimizing of
      the rehabilitative protocol.

PMID- 17036635
TI  - Skin excision and groin lymphadenectomy: techniques and outcomes.
AB  - A 10-year retrospective review of 25 patients undergoing groin lymphadenectomy
      for cutaneous malignancy in the Tayside region of the UK was conducted.
      Comparison was made between patients undergoing the procedure with an elliptical
      incision orientated as a long oblique of at least 4cm width (group 1) and those
      undergoing a similarly oriented incision with no skin excision (group 2). Outcome
      measures including survival, postoperative complications, operative time and
      hospital stay were analyzed. Patients in group I suffered significantly fewer
      complications (p < 0.004) and shorter hospital stay (p < 0.008). Elliptical
      excision of at least 4cm width is our preferred technique for groin
      lymphadenectomy in the treatment of cutaneous malignancy of the lower limb.

PMID- 17036636
TI  - Massive cavernous lymphangioma of the breast and thoracic wall: case report and
      literature review.
AB  - Lymphangiomas are benign lesions but are associated with high morbidity when they
      become very large, occur in critical locations, or when surgically removed,
      develop secondary wound infections. Almost all lesions require surgical
      treatment. Complete excision is curative; however, relapses must be anticipated
      with incomplete excision. We report the case of a patient with a long history of
      massive cavernous lymphangioma of the breast and thoracic wall extending into the
      axilla in whom complete excision was not possible.

PMID- 17036637
TI  - Incidence and characteristics of lymphedema in Turner's syndrome.
AB  - A survey of patients with Turner's syndrome and their parents documents the
      incidence, features, and prognosis of lymphedema in surviving children.

PMID- 17036638
TI  - Restructuring the role of the community pharmacists.

PMID- 17036639
TI  - Taking the fork in the road...and changing the world!

PMID- 17036640
TI  - 2006 Remington Lecture: the pursuit of dignity.

PMID- 17036641
TI  - 2006 Prescott Lecture: lessons learned, lessons shared: what pharmacy needs to do
      to make the most of the profession.

PMID- 17036642
TI  - Prevalence of compounding in independent community pharmacy practice.
AB  - OBJECTIVES: To determine the extent of prescription compounding in independent
      community pharmacies and identify factors that influence the decision of
      independent pharmacists whether to provide compounding services. DESIGN: Cross
      sectional survey. SETTING: Illinois, Missouri, Kansas, and Iowa. PARTICIPANTS:
      370 pharmacists in charge. INTERVENTION: Anonymous questionnaire mailed in
      January 2005. MAIN OUTCOME MEASURES: Percentage of pharmacies that provide
      compounding; percentage of dispensed prescriptions that require compounding;
      factors contributing to decisions whether to provide compounding service.
      RESULTS: Overall, 94% of respondent pharmacies provided compounding services at
      the time of this survey. Prescriptions that required compounding represented less
      than 1% of total prescriptions for the majority (58.3%) of respondents. The main
      reasons for the decision to provide compounding service were wanting to provide
      full pharmaceutical care to patients (73.8% of compounders) and responding to
      requests by prescribers (48.7%). Pharmacies that did not provide compounding
      service cited the main reason as not receiving prescriptions that required
      compounding (63.6% of noncompounders). CONCLUSION: Compounding remains a
      component of pharmacy practice in the independent community setting.
      Prescriptions that required compounding represented 2.3% of all prescriptions
      dispensed by compounding pharmacies.

PMID- 17036643
TI  - Use of self-prescribed nonprescription medications and dietary supplements among
      assisted living facility residents.
AB  - OBJECTIVE: Describe the prevalence of self-prescribed use and misuse as well as
      users' opinions concerning nonprescription medications and dietary supplements in
      assisted living facilities. DESIGN: Descriptive cross-sectional study. SETTING:
      Two assisted living facilities (ALFs) in Oregon and Washington State.
      PARTICIPANTS: Convenience sample of 45 ALF residents. INTERVENTION: Chart reviews
      and face-to-face interviews. MAIN OUTCOME MEASURES: Prevalence and types of use
      of self-prescribed over-the-counter (OTC) medications and dietary supplements;
      misuse of these products, and participants' opinions concerning use of these
      products. RESULTS: Among 29 women and 16 men with a mean (+/- SD) age of 84.8 +/-
      6.9 years and a mean of 9.9 +/- 6.4 years of education, 84.4% were using
      selfprescribed OTC medications and dietary supplements at the time of this study.
      A mean of 3.4 products was used per participant. Nutritional supplements were
      most frequently used (32% of products), followed by gastrointestinal products
      (17%), pain relievers (16.3%), herbals (14.4%), topical products (12%), and
      cold/cough products (8.5%). Potential misuse was identified in 23 (51%) of the
      participants. Problems in the use of products included duplication (70%),
      potential drug/disease/food interactions (20.8%), and other inappropriate use
      (9.1%). The majority (76%) of the participants believed the products were helpful
      in maintaining health, 56% of them wanted more product information, 49% sought
      product information from family and friends, 40% turned to their physicians and
      nurses for information, and 11% asked pharmacists for advice. CONCLUSION: The use
      of nonprescription medications and dietary supplements among ALF residents was
      high, and simultaneous use of multiple products with the same active ingredient
      was the most prevalent problem. The residents turned to family and friends,
      physicians, nurses, and ALF staff for information on these products more
      frequently than they did to pharmacists.

PMID- 17036644
TI  - Identifying caring behaviors of pharmacists through observations and interviews.
AB  - OBJECTIVE: To identify caring behaviors of community pharmacists demonstrated in
      the pharmacist-patient interaction. DESIGN: Qualitative research. SETTING: Five
      community pharmacies in the Greater Chicago area. PARTICIPANTS: 8 pharmacists
      identified as "caring pharmacists" by corporate managers and 13 pharmacy
      technicians. INTERVENTIONS: Observations of pharmacy personnel interacting with
      patients and interviews of 2 pharmacists. MAIN OUTCOME MEASURES: Caring
      behaviors. RESULTS: Four categories of caring behaviors emerged from the
      observation field notes: physical behaviors (leaning toward patient, smiling,
      looking patient in eye), relationship behaviors (greeting patients, knowing name,
      making small talk), task behaviors-nonpharmacy (explaining receipt and money
      transaction), and task behaviors-pharmacy (providing information, calling
      physician, asking about allergies and explaining interactions). In interviews,
      pharmacists said that a caring pharmacist was about "being for the patient," and
      both noted that caring pharmacists greet the patient, inquire about the patient's
      health and family, and are sincerely interested in the patient. Mentors and
      family members are important in developing caring pharmacists, the pharmacists
      said. CONCLUSION: Specific caring behaviors identifiable among pharmacists and
      pharmacy technicians. These behaviors can be modeled by pharmacy managers and
      should be taught in pharmacy schools.

PMID- 17036645
TI  - Implementing personal digital assistant documentation of pharmacist interventions
      in a military treatment facility.
AB  - OBJECTIVE: To describe the use of personal digital assistants (PDAs) in
      documenting pharmacists' clinical interventions. SETTING: Evans Army Community
      Hospital (EACH), a 78-bed military treatment facility, in Colorado Springs.
      PARTICIPANTS: Pharmacists on staff at EACH. PRACTICE DESCRIPTION: All pharmacists
      at EACH used PDAs with the pilot software to record interventions for 1 month.
      The program underwent final design changes and then became the sole source for
      recording pharmacist interventions. The results of this project are being
      evaluated every 3 months for the first year and yearly thereafter. PRACTICE
      INNOVATION: Visual CE (Syware Inc. Cambridge, Mass.) software was selected to
      develop fields for the documentation tool. This software is simple and easy to
      use, and users can retrieve reports of interventions from both inpatient and
      outpatient sections. The software needed to be designed so that data entry would
      only take a few minutes and ad hoc reports could be produced easily. MAIN OUTCOME
      MEASURES: Number of pharmacist interventions reported, time spent in clinical
      interventions, and outcome of clinical intervention. RESULTS: Implementing a PDA
      based system for documenting pharmacist interventions across ambulatory,
      inpatient, and clinical services dramatically increased reporting during the
      first 6 months after implementation (August 2004-February 2005). After initial
      fielding, clinical pharmacists in advanced practice settings (such as disease
      management clinic, anticoagulation clinic) recognized a need to tailor the
      program to their specific activities, which resulted in a spin-off program unique
      to their practice roles. CONCLUSION: A PDA-based system for documenting clinical
      interventions at a military treatment facility increased reporting of
      interventions across all pharmacy points of service. Pharmacy leadership used
      these data to document the impact of pharmacist interventions on safety and
      quality of pharmaceutical care provided.

PMID- 17036646
TI  - Stepwise approach to developing point-of-care testing services in the
      community/ambulatory pharmacy setting.
AB  - OBJECTIVE: To provide a stepwise approach to development and implementation of a
      point-of-care testing (POCT) patient care service. SETTING: Community and
      ambulatory care pharmacy practice. PRACTICE DESCRIPTION: To provide community and
      ambulatory pharmacists with the steps involved in integrating POCT services into
      their pharmacy practice site. PRACTICE INNOVATION: Authors used various resources
      to detail the process of implementing pharmaceutical care in community or
      ambulatory pharmacy settings in combination with individual practice experiences.
      The five steps involved in developing a POCT service include conducting a needs
      assessment, researching and organizing information, developing program materials,
      implementing the service, and evaluating the service. The narrative description
      of each step is illustrated by a case study example. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS/CONCLUSION: POCT
      patient care services are a valuable addition to a pharmacy's services,
      benefiting patients, health care providers, and the pharmacy. This article
      presents a structured, deliberate approach with resources that can be used to
      develop a successful POCT service within a community or ambulatory pharmacy
      setting.

PMID- 17036647
TI  - Preceptors' perspectives on benefits of precepting student pharmacists to
      students, preceptors, and the profession.
AB  - OBJECTIVES: To educate pharmacists on the shortage of quality preceptors and the
      benefits received from precepting; present insights from successful preceptors
      and offer guidance to current and prospective preceptors; and encourage
      pharmacists to become preceptors and mentor aspiring pharmacy professionals.
      SETTING: Advanced experiential settings for Nova Southeastern, Ohio Northern, and
      Creighton Universities. PRACTICE DESCRIPTIONS: Hospital, community, and
      outpatient clinic settings. PRACTICE INNOVATION: Successful incorporation of
      student pharmacists and the experiential process into pharmacy practice. MAIN
      OUTCOME MEASURE: Not applicable. RESULTS: A variety of factors has produced an
      increased demand for qualified pharmacist preceptors, including workload issues,
      an increasing number of pharmacy schools, and an increased experiential load in
      the pharmacy school curricula. Characteristics of quality preceptors include
      demonstrating enthusiasm in their teaching, being open to questions, and
      providing constructive feedback. Sites and preceptors can benefit from teaching
      student pharmacists by receiving assistance in developing and maintaining
      clinical services, sensing the satisfaction of giving back to the profession, and
      material rewards provided by schools of pharmacy. In this article, three
      successful preceptors share their perspectives and insights about precepting, and
      a professional organization perspective is included to highlight the support for
      precepting student pharmacists. CONCLUSION: Additional introductory and advanced
      quality pharmacy experiential practice sites are needed, and pharmacists are
      encouraged to contact nearby pharmacy schools to become preceptors.

PMID- 17036648
TI  - Effect of an automated dispensing system on errors in two pharmacies.

PMID- 17036649
TI  - Feasibility of brief smoking cessation intervention in community pharmacies.

PMID- 17036650
TI  - Pharmacy-physician communications: potential to reduce medication errors.

PMID- 17036651
TI  - Patient education and counseling for drug samples dispensed at physicians'
      offices.

PMID- 17036652
TI  - Ernest Little (1888-1973): champion of the American Foundation for Pharmaceutical
      Education.

PMID- 17036653
TI  - Shingles prevention: vaccine presents opportunity to pharmacists.

PMID- 17036655
TI  - OTC product: WellPatch Migraine.

PMID- 17036654
TI  - New drugs: rasagiline mesylate, conivaptan hydrochloride, and sunitinib malate.

PMID- 17036656
TI  - Lifestyle issues and psoriasis.

PMID- 17036657
TI  - What is your diagnosis? Periungual squamous cell carcinoma.

PMID- 17036658
TI  - Folliculitis decalvans treated with radiation therapy.
AB  - A 33-year-old black man presented with folliculitis decalvans resistant to
      multiple oral and topical therapies. The patient ultimately responded to
      radiation therapy.

PMID- 17036659
TI  - Soft tissue augmentation.
AB  - Recent additions to the soft tissue augmentation armamentarium have greatly
      increased the dermatologic surgeon's choices in optimizing facial contouring and
      the treatment of acne scars. In this article, we review the science of fillers
      and look at the future of dermal fillers.

PMID- 17036660
TI  - Alefacept in the treatment of recalcitrant palmoplantar and erythrodermic
      psoriasis.
AB  - Alefacept is the first biologic agent approved by the US Food and Drug
      Administration for moderate to severe chronic plaque psoriasis. Prior clinical
      studies excluded patients with palmoplantar psoriasis or erythroderma. We report
      2 patients with recalcitrant psoriasis who responded completely to a full course
      of alefacept. One patient presented with severe palmoplantar psoriasis
      recalcitrant to acitretin and methotrexate; another patient presented with
      erythroderma and was transitioned successfully from cyclosporine A. Alefacept
      provides another treatment option for palmoplantar and erythrodermic psoriasis
      and should be considered in the management of patients with these conditions.

PMID- 17036661
TI  - Therapeutic options for herpes labialis: Experimental and natural therapies.

PMID- 17036662
TI  - Cyclopamine: inhibiting hedgehog in the treatment of psoriasis.
AB  - The steroidal alkaloid cyclopamine, a direct inhibitor of the hedgehog (Hh)
      intracellular signaling pathway, has demonstrated promising initial results in
      the treatment of psoriasis. Cyclopamine initially was shown to be effective in
      the induction of the differentiation and apoptosis of basal cell carcinomas
      (BCCs). This brief review explains both the details of Hh signaling and the role
      of cyclopamine in interrupting it. Most importantly, this article discusses the
      implications of recent findings on the treatment of psoriasis. Although
      considerable research and clinical trials lie ahead, cyclopamine-induced Hh
      inhibition may represent the latest mechanistic pathway to combat psoriasis.

PMID- 17036663
TI  - Tinea capitis.
AB  - Tinea capitis (TC) is a common fungal infection of the scalp, hair follicles, and
      hair shafts that can affect any age group but is particularly common in
      schoolchildren. The prevalence of TC has risen in the past 2 decades.
      Griseofulvin, the gold standard of therapy, does not cure about 20% of patients
      with TC, which has led to recent clinical trials on alternative agents for TC.
      This article reviews the pertinent new advances in the understanding of the
      disease and its therapy.

PMID- 17036664
TI  - Sequential use of infliximab and etanercept in generalized pustular psoriasis.
AB  - Generalized pustular psoriasis is a dramatic potentially life-threatening
      psoriasis variant and represents a major therapeutic challenge. Tumor necrosis
      factor alpha (TNF-alpha) inhibitors have been shown to be highly effective in
      psoriasis vulgaris and psoriasis arthritis. Currently, TNF-alpha can be targeted
      therapeutically by 2 different approaches. TNF-alpha antibodies show a fast onset
      of action and a long-lasting activity. Soluble TNF-alpha receptors have a slower
      onset and a shorter duration of activity, which allows a rapid cessation of the
      drug's activity in the case of adverse events. Here we report that a remission of
      generalized pustular psoriasis achieved by the TNF-alpha antibody infliximab was
      maintained by long-term application of the soluble TNF-alpha receptor etanercept.
      Sequential therapy with TNF-alpha antibodies and TNF-alpha receptors may
      represent a novel concept that combines a rapid onset of action in the initiation
      therapy with a lower risk for severe adverse events in the maintenance treatment
      of pustular psoriasis.

PMID- 17036665
TI  - Nonlaser UVB-targeted phototherapy treatment of psoriasis.
AB  - Nonlaser localized narrowband (290-315 nm) UVB phototherapy was tested in 10
      subjects with localized psoriasis. Treatments were given 2 to 3 times weekly.
      Four patients did not complete the planned 25-treatment course. Of the remaining
      6 patients, all reached greater than 90% clearing of their disease. Localized
      nonlaser UVB phototherapy is another option for the treatment of localized
      psoriasis.

PMID- 17036666
TI  - Knowledge and use of evidence-based practice by allied health and health science
      professionals in the United Kingdom.
AB  - Clinical effectiveness (CE) and evidence-based practice (EBP) are the cornerstone
      of modern-day health care. Although many studies have explored attitudes and
      perceived knowledge of individual professions, few have compared these factors
      between professional groups, especially in the allied health professions (AHP)
      and health science services (HSS). We report a study comparing the knowledge and
      practice of 14 different professional groups from the AHP and HSS in terms of EBP
      and CE. The aim was to highlight any differences between the 14 professional
      groups along with the needs of the groups. A postal questionnaire survey was
      completed by a random sample of 1,000 members of AHP and HSS across the United
      Kingdom. There were significant differences between professional groups with, in
      general, professionals from the HSS groups rating their knowledge and application
      of CE and EBP as lower than members of the AHP. Differences were also noted
      between individual professional groups. For example, podiatrists, radiographers,
      and orthoptists reported having less knowledge of CE and EBP than
      physiotherapists, occupational therapists, dietitians, speech and language
      therapists, and psychologists. Barriers to implementing EBP were similar for all
      groups, with lack of both time and money cited as the main issues. A number of
      differences between professions were recorded that highlight the difference in
      educational and policy approach required for greater uptake of EBP.

PMID- 17036667
TI  - Emerging trends on tenure policies and practices in nursing and allied health
      education.
AB  - The tenure system in academia is under attack, and there is a need for empirical
      data on the emerging national trends relating to tenure. This comparative study
      investigated the emerging trends on tenure policies and practices in nursing and
      allied health education. We surveyed the deans of National League for Nursing
      accredited programs and deans of allied health programs belonging to the
      Association of Schools of Allied Health Professions nationwide. The nursing (n =
      187) and allied health (n = 75) deans completed a research questionnaire designed
      to capture the critical issues relating to tenure in higher education. We found
      no significant difference (p > 0.05) between the perceptions of the allied health
      and nursing deans on the policies and practices associated with tenure. The
      allied health and nursing deans had similar views on posttenure review, changes
      in traditional tenure, tenure quota practice, inducements for faculty to forego
      tenure, review of the tenure criteria, and the ranking of the primary criteria
      used in granting tenure. Both groups of deans expressed strong support for the
      tenure system. Overall, 72% of the allied health deans and 68% of the nursing
      deans indicated that a doctorate is the degree required for tenure in their
      institutions. The preponderance of allied health and nursing deans, 77% each,
      ranked teaching as the primary criterion used in tenure decision. On the other
      hand, only 22% of allied health deans and 19% of nursing deans rated research as
      the most important criterion used for tenure. Only 1% of allied health deans and
      4% of nursing deans considered service as the most important criterion used in
      tenure decision. The role of clinical practice in tenure decision was not
      evaluated in our study and is worth investigating in follow-up studies.

PMID- 17036668
TI  - Attitudes and knowledge of students in the allied health professions toward their
      future professional team members.
AB  - The investigators wished to explore final-year allied health students' knowledge
      of their future colleagues. A survey developed by Felsher and Ross (1994) was
      adapted and administered to 35 occupational therapy (OT), 35 physical therapy
      (PT), and 35 speech-language pathology (SLP) students. Findings suggested that
      all students had a good understanding and knowledge of their own professions.
      Differences were found among the three groups of students regarding their
      understanding of other disciplines and the overlap in OT and SLP roles.
      Specifically, OT and SLP students perceived their own professions as the primary
      providers of cognitive treatment. Ways to foster student understanding and
      collaboration are suggested.

PMID- 17036669
TI  - Development of content-valid technical skill assessment instruments for athletic
      taping skills.
AB  - BACKGROUND AND PURPOSE: The content validity of technical skill assessment
      instruments (TSAI) for the skills of athletic taping has not been reported. The
      purpose of this paper is to outline and present the process of content validation
      for nine TSAIs for athletic taping. Local and national validators were selected
      from Canadian Athletic Therapists' Association (CATA)-accredited athletic therapy
      (AT) programs to serve as content validators. METHODS: The process of content
      validation began with the creation of a detailed task analysis via mail and
      simple validation by local validators. Subsequently, the detailed task analysis
      was committee validated by a group of 10 validators from across Canada.
      Validators judged the importance and difficulty of each item, and a face-to-face
      committee-validator meeting established consensus on the majority of checklist
      items. Through a modified Ebel procedure, frequency distribution was used in the
      formation of the final TSAIs. RESULTS: Initial consensus for pre-taping
      assessment and technical skill performance items was low. Upon committee
      discussion and lack of agreement, the decision to remove pretaping assessment
      items was made. Initial results of importance and difficulty for athletic taping
      technical skills were low prior to the committee meeting. Results of importance
      and difficulty improved substantially following the face-to-face committee
      validators meeting. Consensus on fail points improved from initial to final
      committee validation. CONCLUSION: The process of simple and committee validation
      can be seen as effective methods to establish the content validity of instruments
      used for the evaluation of athletic taping.

PMID- 17036670
TI  - Holding doctors responsible at Guantanamo.

PMID- 17036671
TI  - Using the SF-36 to determine perceived health-related quality of life in rural
      Idaho seniors.
AB  - The purpose of this study was to establish the perceived health-related quality
      of life (HRQoL) in people aged 65 and older in rural southeastern Idaho. Ninety
      five people aged 65 and older completed the Short Form 36 version 2 (SF-36 v2), a
      valid and reliable HRQoL instrument. Subject scores were then compared to
      established normative values for the general U.S. adult population and
      specifically to normative values for people aged 65 and older. In general, the
      participant's HRQoL was lower than that of the general population. However,
      females aged 75 and older had higher physical component summary (PCS) scores than
      their age- or gender-matched mates, and PCS scores of all participants aged 75
      and older were higher than those of their age-matched mates. Results of a
      regression analysis indicated that number of prescription medications taken (p =
      0.004) was the only variable predictive of PCS scores. The results of this study
      show a decrease in the physical aspects of HRQoL of participants, signifying that
      HRQoL does decline with age. Results suggest that participants aged 75 and older
      have a higher HRQoL than suspected, which could indicate that rural residence is
      not an immediate indicator of decreased quality of life in the elderly.

PMID- 17036672
TI  - Effects of radiography program admissions practices on student retention.
AB  - This study examined the admissions practices of 24-month radiography programs to
      determine the extent to which the practices affect retention rates. Survey data
      from 327 programs representing 6,443 radiography program matriculants, 5,191
      graduates, and 1,252 withdrawals showed that retention rates were significantly
      (p < or = 0.05) higher in programs that used a competitive admission process than
      in those that did not. Also, it was observed that the use of selective grade
      point average and reference letters in the competitive admission process was
      significant (p < or = 0.05) in predicting increased retention rates in a
      radiography program.

PMID- 17036673
TI  - Duty and liability surrounding clinical internships: What every internship
      coordinator should know.
AB  - Practical work experience has become a common component of many academic
      programs. However, there are risks involved when students engage in required
      academic internships, particularly if these experiences are conducted off-campus.
      In the academic setting, particularly on the campus property, the university has
      an established relationship with the student that carries implied contractual
      duties. The university's duty to the students, which is to provide them with
      educational opportunities and a safe environment, may be upheld even when the
      educational activity is occurring off-campus. Recent court rulings indicate that
      universities may be held liable for students' safety while these students are
      engaged in the fulfillment of education requirements off-campus. Recognizing that
      universities cannot control the behavior and choices of students, universities
      still have a duty to consistently enforce precautionary safety measures and
      forewarn students of any known risks. The delineation and fulfillment of the
      university's duty to provide a safe environment and educational opportunities can
      be addressed through contractual agreements, policies and procedures, and
      communication among the parties. This discussion should assist the internship
      coordinator in establishing policies and procedures that meet the required duties
      and minimize exposure to liability surrounding internships held off-campus.

PMID- 17036674
TI  - Health professions' education and practice: A commentary on transformation
      through the internet.
AB  - The Internet, in all of its forms and functions, is well on the way to becoming
      the most ubiquitous technology of the 21st century. It is changing the way the
      world does business, the way formal education is conducted, and the way humans
      interact with each other. The Internet already has become an invaluable tool for
      formal health education and for the delivery by health professionals of
      information, training, and education to their employees and patients. With new
      paradigms for health on the horizon, modem Internet technologies will transform
      health care practice and systems delivery. In this report, the authors focus
      attention on the use of distance learning/distance education technologies and
      their relationship to, and use in, the health professions.

PMID- 17036675
TI  - Strategies to promote a climate of academic integrity and minimize student
      cheating and plagiarism.
AB  - Student academic misconduct is a growing problem for colleges and universities,
      including those responsible for preparing health professionals. Although the
      implementation of honor codes has had a positive impact on this problem, further
      reduction in student cheating and plagiarism can be achieved only via a
      comprehensive strategy that promotes an institutional culture of academic
      integrity. Such a strategy must combine efforts both to deter and detect academic
      misconduct, along with fair but rigorous application of sanctions against such
      behaviors. Methods useful in preventing or deterring dishonest behaviors among
      students include early integrity training complemented with course-level
      reinforcement, faculty role-modeling, and the application of selected
      testing/assignment preventive strategies, including honor pledges and honesty
      declarations. Giving students more responsibility for oversight of academic
      integrity also may help address this problem and better promote the culture
      needed to uphold its principles. Successful enforcement requires that academic
      administration provide strong and visible support for upholding academic
      integrity standards, including the provision of a clear and fair process and the
      consistent application of appropriate sanctions against those whose conduct is
      found to violate these standards.

PMID- 17036676
TI  - Core competencies for health care professionals.

PMID- 17036677
TI  - The changing face of faculty and governance.

PMID- 17036678
TI  - What ever happened to faculty governance?

PMID- 17036679
TI  - Faculty matters: Jerry White.

PMID- 17036680
TI  - Building a home for the science of nursing education: developing the NLN web
      based repository.

PMID- 17036681
TI  - Defining the professional responsibilities of academic nurse educators: The
      results of a national practice analysis.
AB  - In February 2005, the National League for Nursing's Academic Nurse Educator
      Certification Program and its testing service partner, Applied Measurement
      Professionals, Inc. (AMP), conducted a study designed to determine the
      professional practice responsibilities of academic nurse educators. The results
      of this national practice analysis, reported here, provided the initial
      information required to ensure the development of a practice-related, content
      valid certification examination for academic nurse educators.

PMID- 17036682
TI  - The evolution of educational information systems and nurse faculty roles.
AB  - Institutions of higher education are purchasing and/or designing sophisticated
      administrative information systems to manage such functions as the application,
      admissions, and registration process, grants management, student records, and
      classroom scheduling. Although faculty also manage large amounts of data, few
      automated systems have been created to help faculty improve teaching and learning
      through the management of information related to individual students, the
      curriculum, educational programs, and program evaluation. This article highlights
      the potential benefits that comprehensive educational information systems offer
      nurse faculty.

PMID- 17036683
TI  - Student perceptions of caring in online baccalaureate education.
AB  - The concept of caring in nursing education is foundational. Knowledge development
      regarding caring in face-to-face classroom settings, effective online teaching
      approaches, differences between online and face-to-face classroom settings, and
      supporting student success in online settings is extensive. However, the question
      of whether caring can be effectively conveyed in online nursing classroom
      settings remains unanswered. This qualitative study explored the perceptions of
      one cohort of RN to BSN students regarding how instructors convey caring in
      online education. Thirteen students were emailed surveys consisting of eight open
      ended questions; II students responded. Eight themes emerged from the data:
      frequent feedback, timeliness, reciprocity of caring online, personal connection
      and empathy, clarity, multiple contact opportunities, second-fiddle worries, and
      teacher's commitment to learning.

PMID- 17036684
TI  - Assessing the critical thinking skills of faculty: What do the findings mean for
      nursing education?
AB  - The purpose of this study was twofold: to determine the critical thinking skills
      of nurse faculty and to examine the relationship between epistemological position
      and critical thinking. Most participants reported having no education on critical
      thinking. Data were collected using the California Critical Thinking Skills Test
      (CCTST) and the Learning Environment Preferences (LEP). Findings from the CCTST
      indicated that faculty varied considerably in their ability to think critically;
      LEP findings suggested that participants had not reached the intellectual level
      needed for critical thinking. In addition, 12 faculty participated in one-hour
      telephone interviews in which they described experiences in which students
      demonstrated critical thinking. Despite a lack of clarity on the definition of
      critical thinking, faculty described clinical examples where students engaged in
      analysis, inference, and evaluation. Based on these findings, it is recommended
      that faculty transfer their ability to engage students in critical thinking in
      the clinical setting to the classroom setting. Benchmarks can be established
      based on the ability of faculty to engage in critical thinking.

PMID- 17036685
TI  - The evaluation of students' reflective writing for evidence of critical thinking.
AB  - The purpose of this study was to establish interrater reliability of the Critical
      Thinking Scale (CTS), a teacher-accessible tool designed to measure the critical
      thinking of baccalaureate nursing students as evidenced in their reflective
      writing about their practice experiences.The study is an extension of an earlier
      pilot test of the CTS. Graduating students from a nursing program at a small
      liberal arts college were asked to write about a significant practice experience
      encountered during their last clinical course. Three teachers used the CTS to
      independently evaluate the students' writing. California Critical Thinking Skills
      Test (CCTST) scores provided a standard measure of critical thinking. Results
      indicated statistically significant positive relationships between the CCTST
      total critical thinking score and mean teacher ratings using the CTS.
      Meaningfully significant interrater reliability ratings for the CTS were also
      found. With further development, the CTS has promise as an appropriate tool to
      evaluate students' reflective writing for evidence of critical thinking.

PMID- 17036686
TI  - Got large lecture hall classes? Use clickers.

PMID- 17036688
TI  - A nurse's camaraderie, Compassion, and service in Iraq.

PMID- 17036687
TI  - Executive summary from the Nursing Data Review, Academic Year 2004-2005,
      Baccalaureate, associate degree, and diploma programs.

PMID- 17036689
TI  - Doctor's revenge.

PMID- 17036690
TI  - Mumps, branks and other impediments.

PMID- 17036691
TI  - Medical education at Brown Medical School.

PMID- 17036692
TI  - The Brown Medical School Class of 2006.

PMID- 17036693
TI  - Doctoring: clinical skills teaching in the 21st century.

PMID- 17036694
TI  - So what the heck is an AHEC and what does it mean for Brown?

PMID- 17036695
TI  - Education to improve interdisciplinary practice of health care professionals: a
      pilot project.

PMID- 17036696
TI  - The humble fly: what a model system can reveal about the human biology of aging.

PMID- 17036697
TI  - Science and technology studies: its relevance to medical education and the
      practice of medicine.

PMID- 17036698
TI  - The health of Rhode Island's hospitals.

PMID- 17036699
TI  - New prompt payment regulation offers greater protections to physicians.

PMID- 17036700
TI  - The words of dermatology.

PMID- 17036701
TI  - Healthcare industry representatives: maximizing benefits and reducing risks.

PMID- 17036702
TI  - The oral/systemic connection: where's ECC? What's our role?

PMID- 17036703
TI  - Comparison of mineral trioxide aggregate and calcium hydroxide as pulpotomy
      agents in young permanent teeth (apexogenesis).
AB  - PURPOSE: The purpose of this study was to compare mineral trioxide aggregate
      (MTA) with calcium hydroxide (Ca(OH)2) clinically and radiographically as a
      pulpotomy agent in immature permanent teeth (apexogenesis). METHODS: Fifteen
      children, each with at least 2 immature permanent teeth requiring pulpotomy
      (apexogenesis), were selected for this study. All selected teeth were evenly
      divided into 2 test groups. In group 1, the conventional Ca(OH)2pulpotomy
      (control) was performed, whereas in group 2, the MTA pulpotomy (experimental) was
      done. The children were recalled for clinical and radiographic evaluations after
      3, 6, and 12 months. RESULTS: The follow-up evaluations revealed failure due to
      pain and swelling detected at 6 and 12 months postoperative evaluations in only 2
      teeth treated with Ca(OH)2. The remaining 28 teeth appeared to be clinically and
      radiographically successful 12 months postoperatively. Calcific metamorphosis was
      a radiographic finding in 2 teeth treated with Ca(OH)2 and 4 teeth treated with
      MTA. CONCLUSIONS: Mineral trioxide aggregate showed clinical and radiographic
      success as a pulpotomy agent in immature permanent teeth (apexogenesis) and seems
      to be a suitable alternative to calcium hydroxide.

PMID- 17036704
TI  - Acute ethanol toxicity from ingesting mouthwash in children younger than age 6,
      1989-2003.
AB  - PURPOSE: The purpose of this study was to analyze American Association of Poison
      Control Centers (AAPCC) reports of suspected overingestion of mouthwash by
      children under age 6 and examine the effect of a 1995 Consumer Product Safety
      Commission (CPSC) rule requiring child-resistant packaging for mouthwashes
      containing at least 3 g (0.11 oz) of ethanol per package. METHODS: The volume of
      ethanol ingested per kg of body weight was computed for children at the 5th,
      50th, and 95th percentiles. The potentially toxic and potentially lethal volumes
      of 100% ethanol at each weight were also determined. The authors used segmented
      regression to test the difference in slopes between 1989 to 1996
      (preintervention) and 1996 to 2003 (postintervention). RESULTS: Incidence of
      overingestion rose from a low of 12.7 per 100,000 (1991) to 20.7 (1996). The
      increase ended with the adoption of the CPSC rule, declining to 16.8 per 100,000
      in 2001 and rising to 17.9 in 2003. CONCLUSIONS: This study's analysis suggests
      that the CPSC rule requiring child-resistant packaging on containers of mouthwash
      containing 3 g or more of ethanol has been successful in reducing AAPCC's reports
      of mouthwash overingestion. Health care providers should take a more active role
      by informing parents of the dangers associated with accidental ingestion of
      ethanol-containing mouthwash. Manufacturers should print warnings about the
      potential hazard of high ethanol concentrations on labels more prominent and they
      should stop producing mouthwashes with such high concentrations of ethanol.
      Moreover, they should also consider discontinuing packaging mouthwash in large
      containers.

PMID- 17036705
TI  - Supragingival calculus in children with gastrostomy feeding: significant
      reduction with a caregiver-applied tartar-control dentifrice.
AB  - PURPOSE: This study assessed the anti-calculus benefit of Crest Dual Action
      Whitening Toothpaste in gastrostomy (GT) children compared to a control anti
      caries dentifrice. METHODS: A double-blind randomized crossover design was used
      to compare the two dentifrices. A convenience sample of 24 GT subjects, 3-12
      years old, was given a consensus baseline Volpe-Manhold Index calculus score by 2
      trained examiners, followed by a dental prophylaxis to remove all calculus. Each
      child was randomly assigned to either study or control dentifrice groups.
      Caregivers brushed subjects' teeth twice daily with the unlabelled dentifrice for
      at least 45 seconds. Calculus was scored at 8 weeks (+/- 1 week) by the same
      investigators. Subjects then had a prophylaxis and received the alternative
      dentifrice. Subjects returned 8 weeks (+/- 1 week) later for final calculus
      scoring. RESULTS: The study dentifrice significantly reduced supragingival
      calculus from baseline by 58% compared to control dentifrice (p<0.005 need exact
      p-value unless it is <.001; maybe it's reported in the paper). Calculus levels
      decreased by 68% over the study duration, irrespective of dentifrice. ANOVA found
      no significant differences in calculus scores based on gender, race, history of
      reflux, aspiration pneumonia, or oral intake of food. Calculus was significantly
      related to history of aspiration pneumonia (p<0.05 need exact p-value here).
      CONCLUSION: Crest Dual Action Whitening Toothpaste was effective and better than
      anti-caries control dentifrice in reducing calculus in GT children.

PMID- 17036706
TI  - A cross-sectional study of medication-related factors and caries experience in
      asthmatic children.
AB  - PURPOSE: The purpose of this study was to examine the relationship between the
      specific types of medication, length of use, frequency of use, and dosing time of
      day on the dental caries of children diagnosed with asthma. METHODS: Using a
      patient list from a previous study, surveys were mailed to the parents of 179
      asthmatic children. The survey itself consisted of a table that asked 4
      questions: (1) What combination of asthma medications was used by the subject?
      (2) How long were the medications used? (3) How often were the medications used?
      (4) What time of day were the medications used? RESULTS: Of the 179 surveys that
      were mailed out, 156 were returned. Children who used their medication greater
      than twice daily were significantly more likely to experience dental disease in
      both the primary (odds ratio [OR]=2.56, 95% confidence interval [CI]=1.45-6.29)
      and mixed dentitions (OR=3.56, 95% CI 2.45-5.94). CONCLUSIONS: Increased
      frequency of asthma medication use was associated with increased likelihood of
      caries experience. The time of day asthma medication was used was associated with
      increased likelihood of caries experience in children in the primary dentition.
      Duration of asthma medication use was associated with a decreased likelihood of
      caries experience in children in the mixed dentition.

PMID- 17036707
TI  - Evaluation of initial caries score and caries incidence in a public health
      sealant program: a retrospective study.
AB  - PURPOSE: The purpose of this study was to investigate the relationship between:
      (1) children's caries score (dmft, DMFT) at the time of sealant placement; and
      (2) "success" (measured as being caries-free) of that tooth at follow-up visits.
      METHODS: An existing database of over 38,000 sealants (10,038 children) placed
      between 1997 and 2002 by the Jefferson County Health Department's Community Based
      Sealant Program, Birmingham, Ala, was used in the analysis. Only children
      returning for followup visits after the initial placement of the sealants were
      included in this study, resulting in 6,452 sealants (2,097 children). Logistic
      regression analysis was performed to determine the differences in sealant success
      between children with a dmft score of 0 vs a dmft score of >0 at baseline, and a
      DMFT score of 0 vs a DMFT score of >0 at baseline. RESULTS: In the permanent and
      primary dentitions, those who had no caries at the time of sealant placement
      (dmft/DMFT=0) had a significantly higher success of sealants during years 1 to 5
      compared to those with a caries score of greater than 0 (dmft/DMFT>0; P<.023,
      P<.002, respectively). CONCLUSION: Children with previous caries experience may
      be at a higher risk for sealant "failure" (measured as caries on a tooth surface
      previously sealed) after 1 year and, therefore, may require more diligent sealant
      maintenance.

PMID- 17036708
TI  - Demographics and quality profile of applicants to pediatric dentistry
      residencies.
AB  - PURPOSE: The purpose of this study was to use Postdoctoral Application Support
      Service (PASS) data to study the quality and demographic trends for pediatric
      dentistry residency applicants. METHODS: PASS data on grade point average (GPA)
      and National Dental Board Exam, Part I (NBI) scores were used to determine
      applicant quality. PASS demographic data included: (1) gender; (2) citizenship;
      (3) ethnicity; (4) previous practice of dentistry; and (5) completion of a
      residency or internship. RESULTS: GPAs showed a significant increase for the 6
      years investigated. NBI scores also indicated a significant increase.
      Significantly more females than males applied to pediatric dentistry residencies.
      A significant increase in US/Canadian applicants was found. Ethnicity was similar
      to that of dental school graduates, with minor exceptions. In several of the
      years studied, there were significant differences in applicants who previously
      practiced dentistry or completed a residency/internship vs applicants who had no
      such previous experience. CONCLUSIONS: Significant increases in grade point
      averages and National Dental Board Exam, Part I scores suggest a high quality of
      pediatric dentistry residency applicants and this trend seem to be continuing.
      There are significantly more female than male applicants. More research is
      warranted on actual acceptance data.

PMID- 17036709
TI  - Experience and policy implications of children presenting with dental emergencies
      to US pediatric dentistry training programs.
AB  - PURPOSE: The purpose of this study was to describe and substantiate the
      experience of children, their families, and their caregivers with children's
      dental pain and to explore implications of these experiences for public policy.
      METHODS: Data for 301 children presenting to 35 pediatric dentistry training
      programs during a 1-week period in 2000 for pain relief were collected with a
      questionnaire asking for: (1) sociodemographic characteristics; (2) oral health
      status; (3) dental care history; (4) presenting problem; (5) clinical findings;
      and (6) clinical disposition. Descriptive statistics are presented. RESULTS:
      Among children presenting to training programs with oral pain, 28% were under age
      6, 57% were on Medicaid, and 38% were regarded by their dentists to have "likely
      or obvious" functional impairment-with 22% reporting the highest pain level.
      Parents reported that 59% had "poor or fair oral health" and 29% had a prior
      dental emergency in the previous year. Pain, experienced for several days by 73%
      of children, was associated with difficulty: (1) eating; (2) sleeping; (3)
      attending school; and (4) playing. Parent-reported barriers to seeking dental
      care included: (1) missed work (24%); (2) transportation costs (12%); and (3)
      arranging child care (10%). CONCLUSION: In this study of children with dental
      pain, many suffered significant pain: (1) duration; (2) intensity; (3)
      recurrence; and (4) consequences. This study demonstrates the ongoing need for
      public policies that assure timely, comprehensive, and affordable dental care for
      vulnerable children.

PMID- 17036710
TI  - Knowledge and professional experiences concerning child abuse: an analysis of
      provider and student responses.
AB  - PURPOSE: The objective of this study was to explore dentists', dental
      hygienists', dental students', and dental hygiene students' knowledge about their
      professional responsibilities concerning suspected child abuse and their
      professional experiences with this issue. METHODS: Questionnaire data were
      collected from 220 general dentists, 158 dental hygienists, 233 dental, and 76
      dental hygiene students regarding their knowledge, professional responsibilities,
      and behavior concerning child abuse. RESULTS: Twenty percent of the dentists and
      9% of the dental hygienists had reported at least 1 case of suspected child
      abuse. While 83% of the dental professionals knew that they had to report
      suspected cases of child abuse, only 73% of the students knew their legal
      responsibility. Also, only 28% of the professionals and 18% of the students knew
      where to report suspected child abuse. Compared to students, professionals had
      more knowledge concerning the diagnosis of child abuse, while students were more
      knowledgeable concerning signs of sexual abuse. Professionals, however, were less
      likely to know that failure to report suspected abuse was a misdemeanor.
      CONCLUSION: These data showed that not all dental care providers and students
      were prepared to fulfill their legal and professional responsibilities in these
      situations.

PMID- 17036711
TI  - An in vitro evaluation of the effect of sealant characteristics on laser
      fluorescence for caries detection.
AB  - PURPOSE: The purposes of this study were to: (1) evaluate the ability of a laser
      fluorescence (LF) unit to detect simulated caries under pit and fissure sealants;
      (2) determine the effect of an opacifying agent in sealants on LF values; and (3)
      determine interexaminer reproducibility values of the unit in a highly
      controlled, laboratory setting. Sealant characteristics specifically considered
      were: (1) filler content; (2) opacity; and (3) intrinsic fluorescence. METHODS:
      Three sealants were used in this study: 2 unfilled and 1 filled. To evaluate the
      effect of an opacifying agent, titanium dioxide powder was added to both filled
      and unfilled sealants. 0.5-mm thick sealant discs were prepared for all samples.
      The sealant discs were individually placed on top of 3 wells filled with varying
      amounts of protoporphyrin IX, a fluorescent material that mimicked dental caries.
      A total of 270 readings were made through the different sealant discs to evaluate
      signal attenuation of the laser fluorescence unit. RESULTS: Clear sealants,
      without an added opacifying agent, attenuated LF readings. At baseline
      protoporphyrin IX levels yielding DIAGNOdent readouts of 20 and 60, there was a
      significant difference in the LF readings between the baseline protoporphyrin
      (uncovered) and with sealant disc covered in all 3 sealant types (P<.001).
      Furthermore, the filled sealant attenuated LF signals significantly more than the
      unfilled sealant (P<.001). Sealants with titanium dioxide added had variable
      levels of intrinsic fluorescence. Titanium dioxide added to the sealants also had
      a profound effect on fluorescence transmission of the underlying simulated
      caries. As the concentration of titanium dioxide approached 0.5%, the
      fluorescence signal was almost fully attenuated. CONCLUSION: Clinical detection
      of caries under dental sealants with the use of laser fluorescence units is
      unreliable and not recommended due to a high likelihood of inaccurate readings
      caused by: (1) intrinsic fluorescence of sealant material; and (2) attenuation of
      fluorescence signals by the sealant.

PMID- 17036713
TI  - Engaging children's cooperation in the dental environment through effective
      communication.
AB  - Establishing a trusting relationship with the child patient is a critical
      requisite for the pediatric dentist in gaining the child's cooperation in the
      provision of oral health care. Developing such a relationship is predicated on
      the establishment of effective communication. Many publications in the
      psychological literature, specifically the parenting literature, describe
      communication skills that are relevant to the pediatric dentist in effectively
      communicating with children in the dental environment. Yet, several of these
      approaches to communication are not generally discussed or advocated in the
      dental literature. Among these skills are: (1) reflective listening; (2) self
      disclosing assertiveness; and (3) the use of descriptive praise. This article:
      (1) reviews these 3 skills; (2) describes their theoretical foundations; (3)
      provides examples of when they are useful in the dentist-child clinical
      encounter; and (4) indicates why they are important aspects of the pediatric
      dentist's communication repertoire in establishing a positive, empathetic, and
      mutually cooperative relationship with the child patient.

PMID- 17036712
TI  - Effect of the calibration method of a laser fluorescence device for detecting
      occlusal caries in primary molars.
AB  - PURPOSE: The purpose of this study was to verify the influence of individual
      calibration on sound tooth surfaces and the number of readings on in vitro
      performance of a laser fluorescence (LF) device to detect occlusal caries in
      primary teeth. METHODS: After standard calibration (on the porcelain reference
      object), 72 clinically suspect sites on occlusal surfaces of 54 exfoliated or
      extracted (for orthodontic purposes) primary molars were assessed using the
      DIAGNOdent. First, after individual calibration (on a sound surface of each
      tooth), 3 readings were performed for each site. Subsequently, another 3 readings
      were taken, but without individual calibration on a sound surface of the tooth.
      After these assessments, sites were also evaluated with only one reading after
      individual calibration. Histological validation was performed as the gold
      standard. LF values, sensitivity, specificity, accuracy (number of correct
      diagnosis in both sound and diseased teeth) were calculated and compared using
      the McNemar change test. The area under receiver operating characteristics (ROC)
      curves was also compared. RESULTS: Readings with standard calibration only (mean=
      11.7 +/- 10.6 SD) were significantly higher statistically than assessment with 3
      readings after individual calibration (10.7 +/- 10.7) and with 1 reading (10.2 +/
      8.3) after individual calibration. Nevertheless, sensitivity, specificity,
      accuracy, and area under ROC curve did not change significantly. CONCLUSION:
      Absence of individual calibration does not affect the laser fluorescence device's
      performance in detecting occlusal caries in primary teeth.

PMID- 17036714
TI  - Central hemangioma: an overview and case report.
AB  - Central hemangioma of the mandible and maxilla is extremely rare. Although the
      mucosal and soft tissue lesions are readily suspected by their clinical
      appearance, the intrabony lesions may be difficult to distinguish visually. The
      clinical and radiographic presentation is relatively nonspecific; therefore, a
      proper diagnosis has to be made. The management of central hemangioma is
      difficult because of the abundant vascular network in this region. Various
      therapies have been considered, but surgery has most frequently been used. A case
      report of an 8-year old boy with central hemangioma of the left mandibular body
      with vague clinical features but a characteristic radiographic and histological
      picture of central hemangioma is presented here. Also presented is a literature
      review that includes: (1) clinical features; (2) radiographic appearance; (3)
      histology; and (4) possible treatment modalities. Enbloc resection of the
      mandible was performed, followed by the insertion of a reconstruction plate,
      which will later be replaced by an autogenous graft.

PMID- 17036715
TI  - Changing face of Medicare. As the popular administrator prepares to make his
      exit, providers shouldn't expect much change in direction by his replacement.
AB  - With Mark McClellan poised to exit the CMS, names of possible successors are
      already being floated in Washington, including CMS executive Herb Kuhn, left.
      Observers say whoever takes the job will face some tough challenges, and they
      don't expect much policy to change with Bush still in the White House. "We will
      continue to see what has effectively been gridlock" on many major healthcare
      issues, one said.

PMID- 17036717
TI  - Five years later...9/11 anniversary reveals industry's shortcomings.

PMID- 17036716
TI  - GAO blasts HHS on IT, privacy. But exec argues before there can be 'detailed
      plans', ONCHIT needs a leader.

PMID- 17036718
TI  - Minn. talks universal care.

PMID- 17036719
TI  - Pensions in peril? Law will spur switch to 401(k)-type plans: unions.

PMID- 17036720
TI  - Healthcare insecurity. With voters worried about access, it shouldn't be
      political business as usual.

PMID- 17036721
TI  - Rocky Mountain low. Demise of a provider-owned, Medicaid managed-care plan is
      national harbinger.

PMID- 17036722
TI  - Dealing direct. Private placements--still just a fraction of the debt market-
      have grown more popular by offering providers speed, flexibility.

PMID- 17036723
TI  - Weighty concerns. Bariatric surgery programs on the rebound after initial
      complications.

PMID- 17036724
TI  - Residents still overworked? Studies' findings show polar-opposite conclusions.

PMID- 17036725
TI  - Imclone's next headache.

PMID- 17036726
TI  - Physician, fool thyself. Why the healing power of placebos is making doctors
      think twice.

PMID- 17036728
TI  - Bets on biotech. The nonprofit world steps in to finance for-profit drug
      ventures.

PMID- 17036727
TI  - The power of philanthropy.

PMID- 17036729
TI  - Who pays for special ed?

PMID- 17036730
TI  - A mothers choice.

PMID- 17036731
TI  - Can we keep quality care alive?

PMID- 17036732
TI  - Registered post.
AB  - The professional work of nurses and doctors is subject to a rigorous statutory
      regime of scrutiny. A pilot scheme in Scotland will shortly test out a new
      register for healthcare support workers.

PMID- 17036733
TI  - Being honest.
AB  - Integrity means adhering to high moral principles or professional standards, but
      there are barriers to achieving and maintaining it in nursing.

PMID- 17036734
TI  - Your golden years.

PMID- 17036735
TI  - Getting on with patients.

PMID- 17036736
TI  - Stand up to the bullies.

PMID- 17036737
TI  - More than a feeling.

PMID- 17036738
TI  - Satisfaction guaranteed.

PMID- 17036739
TI  - Spatial requirements in hospital shower and toilet rooms.
AB  - AIM: To determine the spatial requirements for hoist use in an assisted shower
      toilet facility. METHOD: A simulation of two shower-toilet facilities (built
      since 2000) was constructed in a laboratory to compare a mobile hoist and a
      gantry (overhead) hoist for the task of transferring a patient from a wheelchair
      to the toilet. Twenty participants were recruited and trained in the use of both
      hoists. Data were recorded using video cameras and analysed for the space used to
      complete the task, time taken and postural risk scores. RESULTS: The mobile hoist
      needed significantly more space, took significantly longer and exposed the
      handlers to higher postural risks than the overhead hoist. CONCLUSION: Larger
      shower-toilet rooms should be planned and built as accessible facilities with
      sufficient space for independent and assisted wheelchair users. The findings will
      have an impact on the recommendation for increased numbers of single rooms with
      ensuite facilities in new hospitals. Healthcare planners and designers may need
      to consider building specific facilities for assisted wheelchair users rather
      than providing a 'one space fits all' solution.

PMID- 17036740
TI  - Barriers to effective nutritional care for older adults.
AB  - This article reviews the relationship between ageing and nutrition. The
      vulnerability of older adults to nutritional decline is explored and the
      importance of nutritional screening in this population is discussed. The author
      considers some of the barriers to achieving nutritional adequacy once patients
      have been admitted to hospital and suggests how these can be overcome.

PMID- 17036741
TI  - The role of carbohydrates in a healthy diet.
AB  - Nurses have an important role to play in improving patients' diets. This article
      examines the role of carbohydrates in the prevention and management of disease.
      It discusses the qlycaemic response and index, the importance of fibre, insulin
      sensitivity, weight management and the role of resistant starch in healthy
      eating.

PMID- 17036742
TI  - Venepuncture.

PMID- 17036743
TI  - Aide to recovery.

PMID- 17036744
TI  - Statistical analysis of test-day milk yields using random regression models for
      the comparison of feeding groups during the lactation period.
AB  - Random regression models are widely used in the field of animal breeding for the
      genetic evaluation of daily milk yields from different test days. These models
      are capable of handling different environmental effects on the respective test
      day, and they describe the characteristics of the course of the lactation period
      by using suitable covariates with fixed and random regression coefficients. As
      the numerically expensive estimation of parameters is already part of advanced
      computer software, modifications of random regression models will considerably
      grow in importance for statistical evaluations of nutrition and behaviour
      experiments with animals. Random regression models belong to the large class of
      linear mixed models. Thus, when choosing a model, or more precisely, when
      selecting a suitable covariance structure of the random effects, the information
      criteria of Akaike and Schwarz can be used. In this study, the fitting of random
      regression models for a statistical analysis of a feeding experiment with dairy
      cows is illustrated under application of the program package SAS. For each of the
      feeding groups, lactation curves modelled by covariates with fixed regression
      coefficients are estimated simultaneously. With the help of the fixed regression
      coefficients, differences between the groups are estimated and then tested for
      significance. The covariance structure of the random and subject-specific effects
      and the serial correlation matrix are selected by using information criteria and
      by estimating correlations between repeated measurements. For the verification of
      the selected model and the alternative models, mean values and standard
      deviations estimated with ordinary least square residuals are used.

PMID- 17036745
TI  - Different effects of difructose anhydride III and inulin-type fructans on caecal
      microbiota in rats.
AB  - The effects of different kinds of inulin-type fructans on caecal microbiota were
      evaluated in rats. Four groups of male Wistar rats were fed either a control
      diet, or diets containing 5% inulin, 5% fructooligosaccharides (FOS), or 5%
      difructose anhydride III (DFAIII) for two weeks. In the DFAIII group, caecal
      propionate, butyrate, counts of bifidobacteria, and total anaerobes were lower
      than in the inulin group, while caecal propionate, succinate, counts of
      bifidobacteria, and total anaerobes were lower than in the FOS group. Compared to
      controls, in the DFAIII group the counts of clostridia in caecum were increased
      by 3 log units. However, this change was statistically not significant. There
      were no differences between inulin and FOS groups for the pool of short chain
      fatty acids in caecum and bacterial counts. Results indicate that DFAIII has
      different effects on caecal microbiota compared to inulin and FOS and that these
      differences are most likely due to the alpha(3-->2) bonds in DFAIII.

PMID- 17036746
TI  - Effect of bacterial protein meal on protein and energy metabolism in growing
      chickens.
AB  - This experiment investigates the effect of increasing the dietary content of
      bacterial protein meal (BPM) on the protein and energy metabolism, and carcass
      chemical composition of growing chickens. Seventy-two Ross male chickens were
      allocated to four diets, each in three replicates with 0% (D0), 2% (D2), 4% (D4),
      and 6% BPM (D6), BPM providing up to 20% of total dietary N. Five balance
      experiments were conducted when the chickens were 3-7, 10-14, 17-21, 23-27, and
      30-34 days old. During the same periods, 22-h respiration experiments (indirect
      calorimetry) were performed with groups of 6 chickens (period 1), 5 chickens
      (period 2), and one chicken (periods 3-5). After each balance period, one chicken
      in each cage was killed and the carcass weight was recorded. Chemical analyses
      were performed on the carcasses from periods 1, 3, and 5. Weight gain, feed
      intake, and feed conversion rate were found to be similar for all diets. Chickens
      on D0 retained 1.59 g N x kg(-0.75) x d(-1), significantly more than chickens on
      D2, D4, and D6, which retained 1.44 g, 1.52 g, and 1.50 g N x kg(-0.75) x d(-1),
      respectively. This was probably caused by the higher nitrogen content of DO.
      Neither the HE (p = 0.92) nor the retention of energy (p = 0.88) were affected by
      diet. Carcass composition was similar between diets, in line with the values for
      protein and energy retention found in the balance and respiration experiments. It
      was concluded that the overall protein and energy metabolism as well as carcass
      composition were not influenced by a dietary content of up to 6% BPM
      corresponding to 20% of dietary N.

PMID- 17036747
TI  - Influence of benzoic acid and dietary protein level on performance, nitrogen
      metabolism and urinary pH in growing-finishing pigs.
AB  - An experiment was conducted to examine the effect of benzoic acid and two dietary
      protein levels on pig performance, nitrogen balance and urinary pH. A total of 24
      crossbred barrows (26 kg to 106 kg BW) received one of four diets: low protein
      level with and without 1% benzoic acid (LP- and LP+, respectively) and high
      protein level with and without 1% benzoic acid (HP- and HP+, respectively). The
      animals were fed restrictively grower and finisher diets and were kept in
      metabolic cages in weeks 3, 6, 9, and 12 of the experiment. The addition of
      benzoic acid did not improve weight gain and feed conversion ratio. N-intake and
      digested N were only influenced by dietary protein level (p< 0.01), while N
      balance was similar in all four diets. Dietary benzoic acid improved N
      digestibility in the grower period (p<0.01) but not in the finisher period. The
      addition of benzoic acid reduced urinary pH by about one pH-unit in both feeding
      periods independent of the protein level of the diet (p< 0.01) and increased the
      concentration of urinary hippuric acid markedly (p<0.01). The results of this
      study indicate a positive influence of dietary benzoic acid on pigs especially in
      case of feeding a low protein diet in the grower period.

PMID- 17036748
TI  - Influence of different fibre sources on digestibility and nitrogen and energy
      balances in growing pigs.
AB  - The present study was undertaken to investigate how three different fibre
      sources, sugar beet pulp, soya bean hulls and pectin residue, constituting 15% of
      diets for growing pigs, influenced daily body gain, feed conversion, apparent
      faecal digestibility and nitrogen and energy balances. Eight castrated crossbreed
      pigs (30-80 kg live weight) were used in a replicated 4 x 4 Latin-square design
      with one control diet and three fibre containing diets. Daily body weight gain
      and feed conversion were not affected by the dietary treatments. The apparent
      faecal digestibility of organic matter (OM) and energy were significantly lower
      for the fibre diets (OM: 0.81-0.85; energy: 0.78-0.83) compared to the control
      diet (OM: 0.88; energy: 0.86). The apparent faecal digestibility of crude protein
      (CP) was lower for the fibre diets (0.71-0.78) compared to the control diet
      (0.83), although it was only significantly lower for the sugar beet pulp and
      pectin residue diets. The pectin residue diet, which contained the highest amount
      of dietary fibre, lignin and insoluble non-starch polysaccharides, had the lowest
      digestibility of OM, CP and energy. There was a tendency (p = 0.07) for a diet
      effect on retained nitrogen in proportion to digested nitrogen, where the sugar
      beet pulp and pectin residue diets had numerically the highest values. Heat
      production and retained energy in proportion to metabolizable energy intake were
      not affected by fibre inclusion. It was concluded that the inclusion of sugar
      beet pulp, soya bean hulls and pectin residue in diets for growing pigs decreased
      the apparent faecal digestibility and in the diets with sugar beet pulp and
      pectin residue higher utilization of digested nitrogen for retention compensated
      for the lower amount of digested nitrogen.

PMID- 17036749
TI  - Effect of different types of fibre supplemented with sunflower oil on ruminal
      fermentation and production of conjugated linoleic acids in vitro.
AB  - An in vitro study was conducted to determine the effect of different types of
      fibre supplemented with sunflower oil on ruminal fermentation and formation of
      conjugated linoleic acids (CLA) by mixed ruminal microorganisms. Cell wall
      components extracted from wheat straw (representing lignified fibre), soybean
      hulls (representing easily digestible fibre), and purified cellulose were used as
      substrates. Sunflower oil was supplemented at the same level for all three types
      of fibre. After 24 h of incubation, ruminal fermentation parameters (including 24
      h gas production, pH value, concentration of ammonia nitrogen and volatile fatty
      acids) and the concentration of long chain fatty acids in the culture fluid were
      determined. Results showed that the type of fibre influenced ruminal fermentation
      traits and the biohydrogenation of unsaturated C18 fatty acids in vitro.
      Composition of LCFA and profile of CLA were altered by the fibre type. Compared
      to the digestible fibre and purified cellulose, lignified fibre significantly
      increased the production of cis-9, trans-11 CLA and total CLA (sum of cis-9,
      trans-11 CLA, trans-10, cis-12 CLA, trans-9, trans-11 CLA, and cis-9, cis-11 CLA)
      by ruminal microorganisms. It was concluded that ruminal fermentation and
      production of CLA can be affected by the type of dietary fibre.

PMID- 17036750
TI  - In vitro degradation of wheat straw by anaerobic fungi from small ruminants.
AB  - Anaerobic ruminal fungi may play an active role in fibre degradation as evidenced
      by the production of different fibrolytic enzymes in culture filtrate. In the
      present study, 16 anaerobic fungal strains were isolated from ruminal and faecal
      samples of sheep and goats. Based on their morphological characteristics they
      were identified as species of Anaeromyces, Orpinomyces, Piromyces and
      Neocallimastix. Isolated Neocallimastix sp. from goat rumen showed a maximum
      activity of CMCase (47.9 mIU ml(-1)) and filter paper cellulase (48.3 mIU ml(
      1)), while Anaeromyces sp. from sheep rumen showed a maximum xylanolytic activity
      (48.3 mIU ml(-1)). The cellobiase activity for all the isolates ranged from 178.0
      182.7 mIU ml(-1). Based on the enzymatic activities, isolated Anaeromyces sp.
      from sheep rumen and Neocallimastix sp. from goat rumen were selected for their
      potential of in vitro fibre degradation. The highest in vitro digestibility of
      NDF (23.2%) and DM (34.4%) was shown for Neocallimastix sp. from goat rumen, as
      compared to the digestibility of NDF and DM in the control group of 17.5 and
      25.0%, respectively.

PMID- 17036751
TI  - Effects of purified soybean agglutinin on growth and immune function in rats.
AB  - The objective of this study was to investigate the effect of purified soybean
      agglutinin on growth and immune function in rats. Thirty male Sprague-Dawley rats
      (77.8 +/- 2.6 g) were individually fed casein-cornstarch based diets containing
      0, 0.05, 0.10, 0.15 or 0.20% soybean agglutinin (w/w) during a 20-day experiment.
      Growth declined linearly with increasing the concentration of soybean agglutinin
      (p < 0.05). The proliferation of lymphocytes in spleen, lymph nodes and blood
      decreased with an increase in dietary soybean agglutinin (p < 0.05). The
      concentrations of interleukin-2, interferon-gamma and tumor necrosis factor-alpha
      in plasma, spleen, and mesenteric lymph nodes as well as plasma concentrations of
      IgA, IgG and IgM also declined with increasing dose of soybean agglutinin (p <
      0.05). The results show that dietary soybean agglutinin has negative effects on
      growth as well as both cell-mediated and humoral immune function of rats and
      appears to function in a dose-dependent manner.

PMID- 17036752
TI  - Effects of chicken intestinal antimicrobial peptides on humoral immunity of
      chickens and antibody titres after vaccination with infectious bursal disease
      virus vaccine in chicken.
AB  - Sixty chickens were randomly divided into two groups (30 chickens in each group)
      to determine the effect of oral administration of chicken intestinal
      antimicrobial peptides (CIAMP) on the humoral immune response. Chickens of both
      groups were fed the same diet. In the treatment group chickens received drinking
      water supplemented with CIAMP (1 microg/ml) right after hatching. Samples of
      blood, bursa of Fabricus, spleen and intestine were taken at day 1, 4, 7, 10 and
      17 of experiment. CIAMP supplementation enhanced the content of IgG and IgM in
      serum from day 4-10 and day 10-17, respectively, (p < 0.05), IgM-forming cells in
      bursa of Fabricus and spleen at the age of 7 days (p < 0.05) and IgG-forming
      cells in bursa of Fabricus at the age of 4 days (p < 0.05). In addition, CIAMP
      enhanced the IgA-forming cells in caecal tonsils diffuse area at day 4 (p <
      0.05). Furthermore, CIAMP enhanced the antibody response to infectious bursal
      disease virus vaccine (IBDV) in chickens 21 days following IBDV vaccine
      administration (p < 0.05). These results suggested that CIAMP could modulate the
      humoral immune response of chickens and increased the antibody titres of
      infectious bursal disease virus vaccine.

PMID- 17036753
TI  - Efficacy of a herbal product against Histomonas meleagridis after experimental
      infection of turkey poults.
AB  - Histomoniasis (infectious enterohepatitis, blackhead) is caused by the protozoan
      parasite Histomonas meleagridis (H. meleagridis). After the ban of all
      prophylactic and therapeutic drugs in the European Union, histomoniasis is
      increasingly responsible for considerable economic problems to the poultry
      industry. The aim of this study was to investigate the effect of a herbal product
      with extracts from cinnamon, garlic, lemon, and rosemary on H. meleagridis in
      turkey poults in vivo. For this purpose, 60 two-week-old poults were divided into
      three groups. Group 1 received the herbal product in the feed six days before
      infection and in water three days before infection, then in feed and drinking
      water until the end of the experiment. Groups 2 and 3 were left untreated. At
      week 3 of age, Groups 1 and 2 were infected intracloacally with H. meleagridis.
      Three weeks after infection the surviving birds were euthanized and examined for
      pathological lesions. Mortality was 20% in Group 1 and 50% in Group 2. There were
      no deaths in Group 3. DNA of histomonads was detected in all examined caeca and
      livers of the dead birds, but was not detected in any examined organ of the
      surviving birds of all groups. There was no noticeable difference in the lesion
      scores of the dead birds between the groups. The surviving birds of all groups
      did not show lesions post mortem. Since all effective prophylactic and
      therapeutic drugs against histomoniasis were banned in the EU, under given
      conditions the investigated herbal product seems to be an effective alternative
      for the reduction of mortality in turkeys caused by histomoniasis.

PMID- 17036755
TI  - Technology. IT gets HIPAA.

PMID- 17036756
TI  - Finances. Payment makeover.

PMID- 17036757
TI  - Governance. Minority report.

PMID- 17036758
TI  - Nursing. Visas nearing cap.

PMID- 17036759
TI  - Regulation. Thank you, IRS.

PMID- 17036760
TI  - Regulation. 'Big deal' for EHRs.

PMID- 17036761
TI  - Regulation. Make the transfer.

PMID- 17036762
TI  - Data page. Physician use of EMRs is growing.

PMID- 17036763
TI  - A living monument.
AB  - This month marks the five-year anniversary of the Sept. 11 terrorist attacks.And
      its been one year since two hurricanes ripped through the Gulf Coast. How can you
      remember the heroes who gave so much of themselves during those tragic events? By
      being one. Every day.

PMID- 17036764
TI  - Save lives now. 30 things you can do to eliminate infections.
AB  - More than 2 million Americans a year acquire infections during a hospital stay,
      often with deadly results. These infections are costly to treat and difficult to
      rationalize to patients and the public. And most of them can be prevented. Here
      are 30 simple and low-cost things that you can do right now to eliminate
      infections in your hospital. Well outline additional steps in upcoming issues of
      H&HN as part of the 2006 Save Lives Now series.

PMID- 17036765
TI  - Taking stock. Interview by Matthew Weinstock.

PMID- 17036766
TI  - The American Hospital Association-McKesson Quest for Quality Prize 2006 winner.
      Cincinnati Children's Hospital Medical Center. Aiming to be 'the best at getting
      better'.

PMID- 17036767
TI  - Stopping ED violence before it happens.

PMID- 17036768
TI  - Collaboration Seattle style.

PMID- 17036769
TI  - The future of voluntary governance.

PMID- 17036770
TI  - Store-bought lessons.

PMID- 17036771
TI  - Poised for growth. Point-of-care testing.
AB  - The United States is the world's biggest market for diagnostic testing, and one
      of the most active segments within that is point-of-care testing, or POCT. As
      test devices become more compact and easier to use, as well as more accurate,
      tests can be more frequently performed at the point of care, whether that is the
      emergency department, intensive care unit or a patient's home. Among the most
      common tests are those for blood glucose, blood gases, cardiac markers and
      sepsis, as well as pregnancy and ovulation. The biggest advantage of POCT is
      speed. Although home-based point-of-care testing is common, 70 percent of POCT
      takes place in hospitals, doctor's offices and other provider locations, and
      experts predict this segment will grow an average of 15.5 percent each year,
      significantly outpacing home-based testing. This gatefold gives an overview of
      POCT, discusses the challenges, benefits for hospitals, and provides a glimpse of
      what experts believe point-of-care testing will look like in the future.

PMID- 17036772
TI  - The future of the EHR. Connecting across the care continuum. An executive
      dialogue on overcoming the obstacles to a national health information system.

PMID- 17036773
TI  - Democracy is a team sport.

PMID- 17036774
TI  - Artificial disc replacement: progress or hype?

PMID- 17036775
TI  - Advances in osteobiologics in spine surgery.
AB  - In spine surgery, fixation devices that revolutionized spinal fusion are becoming
      mature technologies, and new tools derived from biologics are becoming more
      important in clinical practice. Thus, surgeons need to become more sophisticated
      in evaluating and using these new biologics, which are rapidly entering the
      market. The majority of these biologics are aimed at enhancing spinal fusion and
      can be called osteobiologics. Osteobiologic products vary from recombinant
      proteins to specially prepared allograft or autograft materials. Their financial
      costs are considerable, and the level of proof for the efficacy and safety of
      these products varies widely. In this article, I delineate useful principles that
      can be used to evaluate current and future generations of osteobiologic products,
      and I discuss the most pertinent examples of specific osteobiologics.

PMID- 17036776
TI  - Motion preservation technologies: alternatives to spinal fusion.
AB  - Spinal arthrodesis is a versatile and effective option in the management of
      instabilities, deformities, and painful spinal conditions. An increasing body of
      biomechanical and clinical evidence suggests that the relative immobility of
      fused spinal segments alters stress transfer, leading to adjacent-level
      degeneration. The development of nonfusion spinal prostheses has been driven by
      increasing concerns regarding these arthrodesis-related morbidities, including
      graft-site harvest, pseudarthrosis, and adjacent-level degeneration. Motion
      sparing implants offer some theoretical advantages over fusion; however,
      judicious use of these products with careful patient selection is warranted until
      outcome studies can demonstrate their efficacy. In this article, we review the 3
      major categories of nonfusion technologies: total disc replacement, prosthetic
      nuclear implants, and posterior stabilization devices.

PMID- 17036777
TI  - Reimbursement essentials for the orthopedic practice.

PMID- 17036778
TI  - Hyaluronans: is clinical effectiveness dependent on molecular weight?
AB  - The original rationale for viscosupplementation with hyaluronans was fluid
      replacement, suggesting that the most viscous materials (eg, those of highest
      molecular weight [MW]) would provide the most clinical benefits. However, it has
      become clear that mechanisms of action for osteoarthritis pain management are not
      only mechanical but also biological. After intra-articular injection, hyaluronans
      exert a range of biological actions within the joint. Although high- and low- to
      mid-MW hyaluronans (but not hyaluronans <500 kDa MW) are more or less active
      (depending on the specific effect examined), it is not known which actions are
      clinically meaningful. There is no evidence for a difference between hyaluronan
      products in clinical efficacy measured as pain relief, but investigators in
      several preclinical studies evaluating joint-structure modification in
      osteoarthritis models have reported advantages to using low- to mid-MW
      hyaluronans.

PMID- 17036779
TI  - Autologous hamstring anterior cruciate ligament reconstruction in patients older
      than 40.
AB  - The primary objective in this retrospective review was to assess the patient
      specific outcomes and clinical utility of anterior cruciate ligament (ACL)
      reconstruction using the autologous quadruple-band hamstring technique in
      patients older than 40. Study results agree with the recent literature and
      demonstrate the effectiveness of an alternative to the bone-patellar tendon-bone
      (BPB) technique-an alternative with potentially decreased postoperative
      morbidity. Results also support the recent conclusion that age alone should not
      be a limiting factor in whether ACL reconstruction should be performed. We found
      that appropriately selected patients may experience significant improvements in
      stability, function, and pain after ACL reconstruction with the quadruple-band
      hamstring autograft technique. For outcomes after ACL reconstruction, there seems
      to be no significant difference between the sexes or between patients with and
      without associated injuries in this population. This study also supports use of
      the autologous hamstring technique as a viable option for older patients-with
      results similar to those of the BPB technique. The autologous hamstring technique
      was associated with excellent patient satisfaction and excellent functional
      outcome with limited postoperative morbidity. This technique may become the
      preferred approach for the older athlete, given its limited morbidity and
      equivalent clinical stability.

PMID- 17036780
TI  - A ring transducer system for medical ultrasound research.
AB  - An ultrasonic ring transducer system has been developed for experimental studies
      of scattering and imaging. The transducer consists of 2048 rectangular elements
      with a 2.5-MHz center frequency, a 67% -6 dB bandwidth, and a 0.23-mm pitch
      arranged in a 150-mm-diameter ring with a 25-mm elevation. At the center
      frequency, the element size is 0.30lambda x 42lambda and the pitch is 0.38lambda.
      The system has 128 parallel transmit channels, 16 parallel receive channels, a
      2048:128 transmit multiplexer, a 2048:16 receive multiplexer, independently
      programmable transmit waveforms with 8-bit resolution, and receive amplifiers
      with time variable gain independently programmable over a 40-dB range. Receive
      signals are sampled at 20 MHz with 12-bit resolution. Arbitrary transmit and
      receive apertures can be synthesized. Calibration software minimizes system
      nonidealities caused by noncircularity of the ring and element-to-element
      response differences. Application software enables the system to be used by
      specification of high-level parameters in control files from which low-level
      hardware-dependent parameters are derived by specialized code. Use of the system
      is illustrated by producing focused and steered beams, synthesizing a spatially
      limited plane wave, measuring angular scattering, and forming b-scan images.

PMID- 17036781
TI  - Performance and characterization of new micromachined high-frequency linear
      arrays.
AB  - A new approach for fabricating high frequency (> 20 MHz) linear array
      transducers, based on laser micromachining, has been developed. A 30 MHz, 64
      element, 74-microm pitch, linear array design is presented. The performance of
      the device is demonstrated by comparing electrical and acoustic measurements with
      analytical, equivalent circuit, and finite-element analysis (FEA) simulations.
      All FEA results for array performance have been generated using one global set of
      material parameters. Each fabricated array has been integrated onto a flex
      circuit for ease of handling, and the flex has been integrated onto a custom
      printed circuit board test card for ease of testing. For a fully assembled array,
      with an acoustic lens, the center frequency was 28.7 MHz with a one-way -3 dB and
      -6 dB bandwidth of 59% and 83%, respectively, and a -20 dB pulse width of -99 ns.
      The per-element peak acoustic power, for a +/- 30 V single cycle pulse, measured
      at the 10 mm focal length of the lens was 590 kPa with a -6 dB directivity span
      of about 30 degrees. The worst-case total cross talk of the combined array and
      flex assembly is for nearest neighboring elements and was measured to have an
      average level -40 dB across the -6 dB bandwidth of the device. Any significant
      deviation from simulation can be explained through limitations in apparatus
      calibration and in device packaging.

PMID- 17036782
TI  - Design of a multilayer transducer for acoustic bladder volume assessment.
AB  - Catheterization remains the "gold standard" for bladder volume assessment, but it
      is invasive and introduces the risk of infections and traumas. Therefore,
      noninvasive bladder volume measurement methods have gained interest. In a
      preceding study a new technique to measure the bladder volume on the basis of
      nonlinear ultrasound wave propagation was validated. This paper describes a first
      prototype of a dedicated multilayer transducer to implement this approach. It is
      composed of a PZT transducer for transmission and a PVDF layer for reception.
      Acoustical measurements in a water tank and phantom measurements showed that
      there is a relation between bladder volume and the harmonic contents of the echo
      obtained from a region of interest behind the bladder. Simulations with an
      equivalent transducer model on the basis of KLM-circuit modeling closely matched
      with the results from the acoustical measurements. The results demonstrated the
      feasibility of the multilayer transducer design for bladder volume assessment on
      the basis of nonlinear wave propagation.

PMID- 17036783
TI  - Harmonic 3-D echocardiography with a fast-rotating ultrasound transducer.
AB  - Although the advantages of three-dimensional (3-D) echocardiography have been
      acknowledged, its application for routine diagnosis is still very limited. This
      is mainly due to the relatively long acquisition time. Only recently has this
      problem been addressed with the introduction of new real-time 3-D echo systems.
      This paper describes the design, characteristics, and capabilities of an
      alternative concept for rapid 3-D echocardiographic recordings. The presented
      fast-rotating ultrasound (FRU)-transducer is based on a 64-element phased array
      that rotates with a maximum speed of 8 Hz (480 rpm). The large bandwidth of the
      FRU-transducer makes it highly suitable for tissue and contrast harmonic imaging.
      The transducer presents itself as a conventional phased-array transducer;
      therefore, it is easily implemented on existing 2-D echo systems, without
      additional interfacing. The capabilities of the FRU-transducer are illustrated
      with in-vitro volume measurements, harmonic imaging in combination with a
      contrast agent, and a preliminary clinical study.

PMID- 17036784
TI  - Noninvasive field measurement of low-frequency ultrasonic transducers operating
      in sealed vessels.
AB  - This paper describes a noninvasive technique utilizing the acousto-optic effect,
      laser interferometry, and tomographic principles that have been implemented to
      measure the acoustic fields generated by low-frequency ultrasonic transducers
      operating into sealed, water-loaded vessels commonly used in industrial
      processing applications. A customized scanning frame, incorporating both linear
      and rotational stages, has been developed to facilitate manipulation of the laser
      head and vessel under evaluation. First, transmitted pressure profiles in air are
      predicted from surface displacement data acquired directly by laser measurement
      of the vibrating aperture. These profiles were then used to verify the measured
      fields obtained via conventional tomographic scanning procedures, coupled with
      laser interferometry, applied within a draft-proof scanning facility under free
      field conditions. Next, the finite element code PZF(lex) was employed for the
      prediction of pressure fields within cylindrical cell configurations. Finally,
      precise manipulation of the laser firing angle and position was implemented in
      order to compensate for the effects of refraction at the cell wall boundaries,
      and to re-establish the projections required for the reconstruction algorithm.
      The experimental results demonstrate good corroboration with the PZF(lex)
      predictions, validating its application of ultrasound as a virtual prototyping
      tool for the design of high power ultrasonic test vessels.

PMID- 17036785
TI  - An ultrasound research interface for a clinical system.
AB  - Under a contract with the National Cancer Institute, we have developed a research
      interface to an ultrasound system. This ultrasound research interface (URI) is an
      optional feature providing several basic capabilities not normally available on a
      clinical scanner. The URI can store high-quality beamformed radio-frequency data
      to file for off-line processing. Also, through an integrated user interface, the
      user is provided additional control over the B-mode receive aperture and color
      flow ensemble size. A third major capability is the ability to record and
      playback macro files. In this paper, we describe the URI and illustrate its use
      on three research examples: elastography, computed tomography, and spatial
      compounding.

PMID- 17036786
TI  - The Ultrasonix 500RP: a commercial ultrasound research interface.
AB  - Unlike researchers in magnetic resonance imaging who have considerable access to
      high level tools and to data at a very basic level on their scanners, those
      involved with ultrasound have found little in the way of meaningful and
      widespread access to even the most basic echo signals in their clinical systems.
      Interest has emerged, however, in ultrasound research interfaces on commercial
      scanners to provide access to raw ultrasound data and control of basic research
      functions. This paper describes initial experience gained on one such ultrasound
      system. The Ultrasonix 500RP system provides research access to the data at
      multiple points in the signal processing chain and allows control over most
      imaging parameters. The Ultrasonix system allows for three methods of research
      control. One is implemented along with the standard clinical imaging software
      using "mouseover" screens on the periphery of the application window. These
      screens are configured by the user to display various signal processing
      variables, which can be modified in real time. Second, the system can be
      controlled via a user-written remote control client application interacting
      through the clinical exam software. Lastly, the user can write a complete
      application which initializes the basic ultrasound module but need not use the
      Ultrasonix clinical exam software. All of the modes can be done locally on the
      scanner itself or via a network, and are based on software developed in C++ with
      libraries supplied with the scanner. Two examples are presented in this paper
      from the evaluation of the system in "real world" applications. Measurements of
      absolute backscatter coefficients and attenuation coefficients versus frequency
      are shown and elastograms utilizing spatial compounding are described.

PMID- 17036787
TI  - FEMMINA real-time, radio-frequency echo-signal equipment for testing novel
      investigation methods.
AB  - Fast echographic multiparameter multi-image novel apparatus (FEMMINA), is a
      hardware and software platform dedicated to ultrasonic signal and image
      processing. FEMMINA is able to operate with sequences of radiofrequency (RF)
      frames. Its architecture is designed to be modular, expandable, and aimed at
      implementing different ultrasonic investigation techniques. The first
      experimental characteristic of this system is in its capability to operate in
      real time with ultrasonic RF signals, starting from acquisition up to processing,
      storage, and visualization. The second characteristic is the user-system
      interactivity that allows one to modify the operation appropriately while
      observing results. Currently, FEMMINA works in both typical experimental
      situations to study novel investigation techniques and clinical field to validate
      the proposed methods in different human districts.

PMID- 17036788
TI  - High frame rate imaging system for limited diffraction array beam imaging with
      square-wave aperture weightings.
AB  - A general-purpose high frame rate (HFR) medical imaging system has been
      developed. This system has 128 independent linear transmitters, each of which is
      capable of producing an arbitrary broadband (about 0.05-10 MHz) waveform of up to
      +/- 144 V peak voltage on a 75-ohm resistive load using a 12-bit/40-MHz digital
      to-analog converter. The system also has 128 independent, broadband (about 0.25
      10 MHz), and time-variable-gain receiver channels, each of which has a 12-bit/40
      MHz analog-to-digital converter and up to 512 MB of memory. The system is
      controlled by a personal computer (PC), and radio frequency echo data of each
      channel are transferred to the same PC via a standard USB 2.0 port for image
      reconstructions. Using the HFR imaging system, we have developed a new limited
      diffraction array beam imaging method with square-wave aperture voltage
      weightings. With this method, in principle, only one or two transmitters are
      required to excite a fully populated two-dimensional (2-D) array transducer to
      achieve an equivalent dynamic focusing in both transmission and reception to
      reconstruct a high-quality three-dimensional image without the need of the time
      delays of traditional beam focusing and steering, potentially simplifying the
      transmitter subsystem of an imager. To validate the method, for simplicity, 2-D
      imaging experiments were performed using the system. In the in vitro experiment,
      a custom-made, 128-element, 0.32-mm pitch, 3.5-MHz center frequency linear array
      transducer with about 50% fractional bandwidth was used to reconstruct images of
      an ATS 539 tissue-mimicking phantom at an axial distance of 130 mm with a field
      of view of more than 90 degrees. In the in vivo experiment of a human heart,
      images with a field of view of more than 90 degrees at 120-mm axial distance were
      obtained with a 128-element, 2.5-MHz center frequency, 0.15-mm pitch Acuson V2
      phased array. To ensure that the system was operated under the limits set by the
      U.S. Food and Drug Administration, the mechanical index, thermal index, and
      acoustic output were measured. Results show that higher-quality images can be
      reconstructed with the square-wave aperture weighting method due to an increased
      penetration depth as compared to the exact weighting method developed previously,
      and a frame rate of 486 per second was achieved at a pulse repetition frequency
      of about 5348 Hz for the human heart.

PMID- 17036789
TI  - A programmable real-time system for development and test of new ultrasound
      investigation methods.
AB  - In vitro and/or in vivo experimental tests represent a crucial phase in the
      development of new ultrasound (US) investigation methods for biomedical
      applications. Such tests frequently are made difficult by the lack of flexibility
      of general purpose instruments and commercial US machines typically available in
      research laboratories. This paper presents a novel, real-time development system
      specifically designed for US research purposes. Main features of the system are
      the limited dimensions (it is based on a single electronic board), the capability
      of transmitting arbitrary waveforms to two probes, of storing the received radio
      frequency (RF) echo data in a file and/or of processing them in real-time
      according to programmable algorithms. As an example of application, results of
      simultaneous hemodynamic and mechanic investigations in human arteries are
      reported. However, the high system flexibility and portability make it suitable
      for a large class of US applications.

PMID- 17036790
TI  - The progressive focusing correction technique for ultrasound beamforming.
AB  - This work presents a novel method for digital ultrasound beamforming based on
      programmable table look-ups, in which vectors containing coded focusing
      information are efficiently stored, achieving an information density of a
      fraction of bit per acquired sample. Timing errors at the foci are within half
      the period of a master clock of arbitrarily high frequency to improve imaging
      quality with low resource requirements. The technique is applicable with
      conventional as well as with deltasigma converters. The bit-width of the focusing
      code and the number of samples per focus can be defined to improve both memory
      size and F# with controlled timing errors. In the static mode, the number of
      samples per focus is fixed, and in the dynamic approach that figure grows
      progressively, taking advantage of the increasing depth of focus. Furthermore,
      the latter has the lowest memory requirements. The technique is well suited for
      research purposes as well as for real-world applications, offering a degree of
      freedom not available with other approaches. It allows, for example, modifying
      the sampling instants to phase aberration correction, beamforming in layered
      structures, etc. The described modular and scalable prototype has been built
      using low-cost field programmable gate arrays (FPGAs). Experimental measurements
      are in good agreement with the theoretically expected errors.

PMID- 17036791
TI  - Adaptive imaging on a diagnostic ultrasound scanner at quasi real-time rates.
AB  - Constructing an ultrasonic imaging system capable of compensating for phase
      errors in real-time is a significant challenge in adaptive imaging. We present a
      versatile adaptive imaging system capable of updating arrival time profiles at
      frame rates of approximately 2 frames per second (fps) with 1-D arrays and up to
      0.81 fps for 1.75-D arrays, depending on the desired near-field phase correction
      algorithm. A novel feature included in this system is the ability to update the
      aberration profile at multiple beam locations for 1-D arrays. The features of
      this real-time adaptive imaging system are illustrated in tissue-mimicking
      phantoms with physical near-field phase screens and evaluated in clinical breast
      tissue with a 1.75-D array. The contrast-to-noise ratio (CNR) of anechoic cysts
      was shown to improve dramatically in the tissue-mimicking phantoms. In breast
      tissue, the width of point-like targets showed significant improvement: a
      reduction of 26.2% on average. Brightness of these targets, however, marginally
      decreased by 3.9%. For larger structures such as cysts, little improvement in
      features and CNR were observed, which is likely a result of the system assuming
      an infinite isoplanatic patch size for the 1.75-D arrays. The necessary
      requirements for constructing a real-time adaptive imaging system are also
      discussed.

PMID- 17036792
TI  - Intravascular ultrasound tissue harmonic imaging in vivo.
AB  - Tissue harmonic imaging (THI) has been shown to increase image quality of medical
      ultrasound in the frequency range from 2 to 10 MHz and might, therefore, also be
      used to improve image quality in intravascular ultrasound (IVUS). In this study
      we constructed a prototype IVUS system that could operate in both fundamental
      frequency and second harmonic imaging modes. This system uses a conventional,
      continuously rotating, single-element IVUS catheter and was operated in
      fundamental 20 MHz, fundamental 40 MHz, and harmonic 40 MHz modes (transmit 20
      MHz, receive 40 MHz). Hydrophone beam characterization measurements demonstrated
      the build-up of a second harmonic signal as a function of increasing pressure.
      Imaging experiments were conducted in both a tissue-mimicking phantom and in an
      atherosclerotic animal model in vivo. Acquisitions of fundamental 20 and 40 MHz
      and second harmonic acquisitions resulted in cross sections of the phantom and a
      rabbit aorta. The harmonic results of the imaging experiments showed the
      feasibility of intravascular THI with a conventional IVUS catheter both in a
      phantom and in vivo. The harmonic acquisitions also showed the potential of THI
      to reduce image artifacts compared to fundamental imaging.

PMID- 17036793
TI  - Multigate transcranial Doppler ultrasound system with real-time embolic signal
      identification and archival.
AB  - An integrated system for acquisition and processing of intracranial and
      extracranial Doppler signals and automatic embolic signal detection has been
      developed. The hardware basis of the system is a purpose-built
      acquisition/processing board that includes a multigate Doppler unit controlled
      through a computer. The signal-processing engine of the system contains a fast
      Fourier transform (FFT)-based, spectral-analysis unit and an embolic signal
      detection unit using expert system reasoning theory. The system is designed so
      that up to four receive gates from a single transducer can be used to provide
      useful reasoning information to the embolic signal-detection unit. Alternatively,
      two transducers can be used simultaneously, either for bilateral transcranial
      Doppler (TCD) investigations or for simultaneous intra- and extracranial
      investigation of different arteries. The structure of the software will allow the
      future implementation of embolus detection algorithms that use the information
      from all four channels when a single transducer is used, or of independent
      embolus detection in two sets of two channels when two transducers are used. The
      user-friendly system has been tested in-vitro, and it has demonstrated a 93.6%
      sensitivity for micro-embolic signal (MES) identification. Preliminary in-vivo
      results also are encouraging.

PMID- 17036795
TI  - Trajectory tracking of piezoelectric positioning stages using a dynamic sliding
      mode control.
AB  - Trajectory tracking performance of a piezoelectric positioning stage almost
      depends on whether the tracking controller can effectively compensate the
      inherent hysteresis phenomenon. In this paper, a dynamic sliding-mode control
      (DSMC) with backstepping is proposed for the trajectory tracking of the
      piezoelectric positioning stage, which is suitable for a component of scanning
      microscopes. An equivalent model developed from a linear motion dynamics with
      addition of the hysteresis nonlinearity and strain-dependent function first is
      proposed to approximately represent the dynamics of motion of a one-dimensional
      piezoelectric positioning stage. Then, based on the equivalent model, the DSMC
      with an asymptotical sliding surface is proposed for the trajectory tracking
      control of the piezoelectric positioning stage. Moreover, the analysis of
      stability can be completed by mathematics, and the convergence rate of the
      tracking error can be governed by the choice of the control parameter values.
      Using the DSMC to trajectory tracking control, the piezoelectric positioning
      stage becomes more suitable for practical applications, especially with the need
      of various trajectories tracking in microscopy. To validate the proposed control
      scheme, a computer-based controller and a piezoelectric positioning stage with a
      capacitive displacement sensor are implemented. Experimental results illustrate
      the feasibility of the proposed controller for trajectory tracking applications.

PMID- 17036794
TI  - High reliability outdoor sonar prototype based on efficient signal coding.
AB  - Many mobile robots and autonomous vehicles designed for outdoor operation have
      incorporated ultrasonic sensors in their navigation systems, whose function is
      mainly to avoid possible collisions with very close obstacles. The use of these
      systems in more precise tasks requires signal encoding and the incorporation of
      pulse compression techniques that have already been used with success in the
      design of high-performance indoor sonars. However, the transmission of ultrasonic
      encoded signals outdoors entails a new challenge because of the effects of
      atmospheric turbulence. This phenomenon causes random fluctuations in the phase
      and amplitude of traveling acoustic waves, a fact that can make the encoded
      signal completely unrecognizable by its matched receiver. Atmospheric turbulence
      is investigated in this work, with the aim of determining the conditions under
      which it is possible to assure the reliable outdoor operation of an ultrasonic
      pulse compression system. As a result of this analysis, a novel sonar prototype
      based on complementary sequences coding is developed and experimentally tested.
      This encoding scheme provides the system with very useful additional features,
      namely, high robustness to noise, multi-mode operation capability (simultaneous
      emissions with minimum cross talk interference), and the possibility of applying
      an efficient detection algorithm that notably decreases the hardware resource
      requirements.

PMID- 17036796
TI  - Complex permittivity measurements of ferroelectrics employing composite
      dielectric resonator technique.
AB  - Composite cylindrical TE(0n1) mode dielectric resonator has been used for the
      complex permittivity measurements of ferroelectrics at frequency about 8.8 GHz.
      Rigorous equations have been derived that allowed us to find a relationship
      between measured resonance frequency and Q-factor and the complex permittivity.
      It has been shown that the choice of appropriate diameter of a sample together
      with rigorous complex angular frequency analysis allows precise measurements of
      various ferroelectric. Proposed technique can be used for materials having both
      real and imaginary part of permittivity as large as a few thousand. Variable
      temperature measurements were performed on a PbMg(1/3)Nb(2/3)O3 (PMN) ceramic
      sample, and the measured complex permittivity have shown good agreement with the
      results of measurements obtained on the same sample at lower frequencies (0.1-1.8
      GHz).

PMID- 17036797
TI  - Merits of PM noise measurement over noise figure: a study at microwave
      frequencies.
AB  - This paper primarily addresses the usefulness of phase-modulation (PM) noise
      measurements versus noise figure (NF) measurements in characterizing the merit of
      an amplifier. The residual broadband (white PM) noise is used as the basis for
      estimating the NF of an amplifier. We have observed experimentally that many
      amplifiers show an increase in the broadband noise of 1 to 5 dB as the signal
      level through the amplifier increases. This effect is linked to input power
      through the amplifier's nonlinear intermodulation distortion. Consequently, this
      effect is reduced as linearity is increased. We further conclude that, although
      NF is sometimes used as a selection criteria for an amplifier for low-level
      signal, NF yields no information about potentially important close-to-carrier 1/f
      noise of an amplifier nor broadband noise in the presence of a high-level signal,
      but a PM noise measurements does. We also have verified experimentally that the
      single-sideband PM noise floor of an amplifier due to thermal noise is -177
      dBc/Hz, relative to a carrier input power of 0 dBm.

PMID- 17036798
TI  - Finite difference time domain methods for piezoelectric crystals.
AB  - The numerical simulation of acoustic wave propagation through piezoelectric
      crystals using the finite-difference time-domain (FDTD) method is introduced. The
      update equations for the velocity and stress fields are derived and applied to
      the propagation of ultrasonic waves in three substrates. The concept of the
      perfectly matched layer (PML), first introduced for the simulation of
      electromagnetic waves, is extended to the simulation of mechanical waves. The
      technique is shown to be effective for some crystals, but the PML is found to
      exhibit numerical instabilities for others.

PMID- 17036799
TI  - Blind multiridge detection for automatic nondestructive testing using ultrasonic
      signals.
AB  - Ultrasonic imaging has been a significant means for nondestructive testing (NDT).
      Recently the NDT techniques via the ultrasonic instrumentation have shown the
      striking capability of the quality control for the material fabrication industry.
      To the best of our knowledge, all existing signal processing methods require
      either the a priori information of the ultrasonic signature signals or the manual
      segmentation operation to achieve the reliable parameters that characterize the
      corresponding mechanical properties. In this paper, we first provide a general
      mathematical model for the ultrasonic signals collected by the pulse-echo
      sensors, then design a totally blind novel signal processing NDT technique
      relying on neither a priori signal information nor any manual effort. Based on
      the automatic selection of optimal frame sizes using a proposed new criterion in
      our scheme, the signature signal can be blindly extracted for further robust
      multiridge detection. The detected ridge information can be used to estimate the
      transmission and attenuation coefficients associated with any arbitrary material
      sample for the fabrication quality control.

PMID- 17036800
TI  - Suppression of reflection coefficients of surface acoustic wave filters using
      quadrature hybrids.
AB  - This paper proposes a simple technique to suppress the reflection coefficients
      S11 and S22 of surface acoustic wave (SAW) filters. Two identical SAW filters are
      sandwiched in between two quadrature hybrids, where their two ports are used as
      input and output, and others are terminated by matched loads. First, it is shown
      by simulation that both [S11] and [S22] are suppressed to be less than -20 dB
      without deteriorating the transmission characteristics. Next, two hybrids using
      microstrip lines were fabricated, and two RF SAW filters for GSM850 were
      sandwiched in between them. The result showed that the maximum [S11] within the
      passband was improved from -12.5 dB to -21.7 dB, i.e., 9.2 dB suppression of
      [S11] was achieved by sacrificing only the insertion loss of less than 0.6 dB. We
      also attempted to replace the microstrip lines with lumped elements. In this
      case, the maximum [S11] within the passband was improved more than 7.5 dB with
      the increased insertion loss of less than 1.5 dB. Finally, simple discussion is
      given on the inclusion of the transformer function in the quadrature hybrid.

PMID- 17036801
TI  - Comparison of conventional and collapsed region operation of capacitive
      micromachined ultrasonic transducers.
AB  - We report experimental results from a comparative study on collapsed region and
      conventional region operation of capacitive micromachined ultrasonic transducers
      (CMUTs) fabricated with a wafer bonding technique. Using ultrasonic pulse-echo
      and pitch-catch measurements, we characterized single elements of 1-D CMUT arrays
      operating in oil. The experimental results from this study agreed with the
      simulation results: a CMUT operating in the collapsed region produced a higher
      maximum output pressure than a CMUT operated in the conventional region at 90% of
      its collapse voltage (3 kPa/V vs. 16.1 kPa/V at 2.3 MHz). While the pulse-echo
      fractional bandwidth (126%) was higher in the collapsed region operation than in
      the conventional operation (117%), the pulse-echo amplitude in collapsed region
      operation was 11 dB higher than in conventional region operation. Furthermore,
      within the range of tested bias voltages, the output pressure monotonously
      increased with increased bias during collapsed region operation. It was also
      found that in the conventional mode, short AC pulses (larger than the collapse
      voltage) could be applied without collapsing the membranes. Finally, while no
      significant difference was observed in reflectivity of the CMUT face between the
      two regions of operation, hysteretic behavior of the devices was identified in
      the collapsed region operation.

PMID- 17036802
TI  - Study of the bending modes in circular quartz resonators.
AB  - An experimental and theoretical study of bending modes in a partially electroded
      circular piezoelectric quartz (AT-cut) with free edge is presented. The quartz is
      excited by a voltage pulse applied on the electrodes, and its surface is scanned
      by a laser vibrometer that measures the out-of-plane displacements. The classical
      theory of bending of thin disks is used to describe the flexural modes at
      frequencies lower than the first thickness shear resonance (6 MHz). A fairly good
      agreement is found between experimental and theoretical results for the forced
      mode shapes and for the resonance frequencies. However, it appears that the two
      springs used to maintain the disk in position introduce extra clamping
      conditions. Several source shapes were studied, among which a collection of an
      arbitrary number of forces is particularly useful. The two-dimensional wavenumber
      representation shows the presence of anisotropy related to the crystallographic
      axes at higher frequencies, which is not predicted by the model. The experimental
      phase velocities are compared to those given by the classical theory of disks and
      to those of Lamb A(0) mode. This study confirms the correspondence at low
      frequencies between the A(0) mode and the bending eigenmodes of a disk with
      finite size.

PMID- 17036803
TI  - Beam steering with segmented annular arrays.
AB  - Two-dimensional (2-D) arrays of squared matrix have maximum periodicity in their
      main directions; consequently, they require half wavelength (lambda/2),
      interelement spacing to avoid grating lobes. This condition gives rise to well
      known problems derived from the huge number of array elements and from their
      small size. In contrast, 2-D arrays with curvilinear configuration produce lower
      grating lobes and, therefore, allow the element size to be increased beyond
      lambda/2. Using larger elements, these arrays have the advantage of reducing the
      number of elements and of increasing the signal-to-noise ratio (SNR). In this
      paper, the beamforming properties of segmented annular phased arrays are
      theoretically analyzed and compared with the equivalent squared matrix array. In
      the first part, point-like elements are considered in order to facilitate the
      field analysis with respect to the array structure. Afterward, the effect of the
      element size on the steered beam properties also is presented. In the examples,
      it is shown that the segmented annular array has notably lower grating lobes than
      the equivalent squared matrix array and that it is possible to design segmented
      annular arrays with interelement distance higher than lambda whose beam
      characteristics are perfectly valid for volumetric imaging applications.

PMID- 17036804
TI  - Photoacoustic flow measurements with gold nanoparticles.
AB  - The hypothesis that quantitative blood flow measurements are feasible with the
      time-intensity based method in photoacoustic imaging using gold nanoparticles as
      contrast agent is experimentally tested. The in vitro results show good linearity
      between the measurements and the theory, thus suggesting the potential of
      relative photoacoustic flow measurements with gold nanoparticles.

PMID- 17036805
TI  - Effects of piezoelectric coupling on Bechmann's number for thickness-twist waves
      in a plate of hexagonal crystals.
AB  - Solutions for thickness-twist waves in a piezoelectric plate of 6-mm crystals
      with surface mass layers are obtained. The solutions are used to determine
      Bechmann's number for designing electrode size of devices operating with these
      waves. This generalizes the existing knowledge on Bechmann's number by the
      inclusion of piezoelectric coupling. It is shown that this coupling plays a role
      as important as or more important than the electrode inertia. The results are of
      fundamental importance to resonator design, in particular thin film resonators of
      ZnO and AlN.

PMID- 17036806
TI  - Evaluating sensor reliability in classification problems based on evidence
      theory.
AB  - This paper presents a new framework for sensor reliability evaluation in
      classification problems based on evidence theory (or the Dempster-Shafer theory
      of belief functions). The evaluation is treated as a two-stage training process.
      First, the authors assess the static reliability from a training set by comparing
      the sensor classification readings with the actual values of data, which are both
      represented by belief functions. Information content contained in the actual
      values of each target is extracted to determine its influence on the evaluation.
      Next, considering the ability of the sensor to understand a dynamic working
      environment, the dynamic reliability is evaluated by measuring the degree of
      consensus among a group of sensors. Finally, the authors discuss why and how to
      combine these two kinds of reliabilities. A significant improvement using the
      authors' method is observed in numerical simulations as compared with the
      recently proposed method.

PMID- 17036807
TI  - A probabilistic model for binaural sound localization.
AB  - This paper proposes a biologically inspired and technically implemented sound
      localization system to robustly estimate the position of a sound source in the
      frontal azimuthal half-plane. For localization, binaural cues are extracted using
      cochleagrams generated by a cochlear model that serve as input to the system. The
      basic idea of the model is to separately measure interaural time differences and
      interaural level differences for a number of frequencies and process these
      measurements as a whole. This leads to two-dimensional frequency versus time
      delay representations of binaural cues, so-called activity maps. A probabilistic
      evaluation is presented to estimate the position of a sound source over time
      based on these activity maps. Learned reference maps for different azimuthal
      positions are integrated into the computation to gain time-dependent discrete
      conditional probabilities. At every timestep these probabilities are combined
      over frequencies and binaural cues to estimate the sound source position. In
      addition, they are propagated over time to improve position estimation. This
      leads to a system that is able to localize audible signals, for example human
      speech signals, even in reverberating environments.

PMID- 17036808
TI  - Design and stabilization of sampled-data neural-network-based control systems.
AB  - This paper presents the design and stability analysis of a sampled-data neural
      network-based control system. A continuous-time nonlinear plant and a sampled
      data three-layer fully connected feedforward neural-network-based controller are
      connected in a closed loop to perform the control task. Stability conditions will
      be derived to guarantee the closed-loop system stability. Linear-matrix
      inequality- and genetic-algorithm-based approaches will be employed to obtain the
      largest sampling period and the connection weights of the neural network subject
      to the considerations of the system stability and performance. An application
      example will be given to illustrate the design procedure and effectiveness of the
      proposed approach.

PMID- 17036809
TI  - Evolving compact and interpretable Takagi-Sugeno fuzzy models with a new encoding
      scheme.
AB  - Developing Takagi-Sugeno fuzzy models by evolutionary algorithms mainly requires
      three factors: an encoding scheme, an evaluation method, and appropriate
      evolutionary operations. At the same time, these three factors should be designed
      so that they can consider three important aspects of fuzzy modeling: modeling
      accuracy, compactness, and interpretability. This paper proposes a new
      evolutionary algorithm that fulfills such requirements and solves fuzzy modeling
      problems. Two major ideas proposed in this paper lie in a new encoding scheme and
      a new fitness function, respectively. The proposed encoding scheme consists of
      three chromosomes, one of which uses unique chained possibilistic representation
      of rule structure. The proposed encoding scheme can achieve simultaneous
      optimization of parameters of antecedent membership functions and rule structures
      with the new fitness function developed in this paper. The proposed fitness
      function consists of five functions that consider three evaluation criteria in
      fuzzy modeling problems. The proposed fitness function guides evolutionary search
      direction so that the proposed algorithm can find more accurate compact fuzzy
      models with interpretable antecedent membership functions. Several evolutionary
      operators that are appropriate for the proposed encoding scheme are carefully
      designed. Simulation results on three modeling problems show that the proposed
      encoding scheme and the proposed fitness functions are effective in finding
      accurate, compact, and interpretable Takagi-Sugeno fuzzy models. From the
      simulation results, it is shown that the proposed algorithm can successfully find
      fuzzy models that approximate the given unknown function accurately with a
      compact number of fuzzy rules and membership functions. At the same time, the
      fuzzy models use interpretable antecedent membership functions, which are helpful
      in understanding the underlying behavior of the obtained fuzzy models.

PMID- 17036810
TI  - Generalized disjunction decomposition for evolvable hardware.
AB  - Evolvable hardware (EHW) refers to self-reconfiguration hardware design, where
      the configuration is under the control of an evolutionary algorithm (EA). One of
      the main difficulties in using EHW to solve real-world problems is scalability,
      which limits the size of the circuit that may be evolved. This paper outlines a
      new type of decomposition strategy for EHW, the "generalized disjunction
      decomposition" (GDD), which allows the evolution of large circuits. The proposed
      method has been extensively tested, not only with multipliers and parity bit
      problems traditionally used in the EHW community, but also with logic circuits
      taken from the Microelectronics Center of North Carolina (MCNC) benchmark library
      and randomly generated circuits. In order to achieve statistically relevant
      results, each analyzed logic circuit has been evolved 100 times, and the average
      of these results is presented and compared with other EHW techniques. This
      approach is necessary because of the probabilistic nature of EA; the same logic
      circuit may not be solved in the same way if tested several times. The proposed
      method has been examined in an extrinsic EHW system using the (1 + lambda)
      evolution strategy. The results obtained demonstrate that GDD significantly
      improves the evolution of logic circuits in terms of the number of generations,
      reduces computational time as it is able to reduce the required time for a single
      iteration of the EA, and enables the evolution of larger circuits never before
      evolved. In addition to the proposed method, a short overview of EHW systems
      together with the most recent applications in electrical circuit design is
      provided.

PMID- 17036811
TI  - Design and control of an IPMC wormlike robot.
AB  - This paper presents an innovative wormlike robot controlled by cellular neural
      networks (CNNs) and made of an ionic polymer-metal composite (IPMC) self-actuated
      skeleton. The IPMC actuators, from which it is made of, are new materials that
      behave similarly to biological muscles. The idea that inspired the work is the
      possibility of using IPMCs to design autonomous moving structures. CNNs have
      already demonstrated their powerfulness as new structures for bio-inspired
      locomotion generation and control. The control scheme for the proposed IPMC
      moving structure is based on CNNs. The wormlike robot is totally made of IPMCs,
      and each actuator has to carry its own weight. All the actuators are connected
      together without using any other additional part, thereby constituting the robot
      structure itself. Worm locomotion is performed by bending the actuators
      sequentially from "tail" to "head," imitating the traveling wave observed in real
      world undulatory locomotion. The activation signals are generated by a CNN. In
      the authors' opinion, the proposed strategy represents a promising solution in
      the field of autonomous and light structures that are capable of reconfiguring
      and moving in line with spatial-temporal dynamics generated by CNNs.

PMID- 17036812
TI  - Control architecture for human-robot integration: application to a robotic
      wheelchair.
AB  - Completely autonomous performance of a mobile robot within noncontrolled and
      dynamic environments is not possible yet due to different reasons including
      environment uncertainty, sensor/software robustness, limited robotic abilities,
      etc. But in assistant applications in which a human is always present, she/he can
      make up for the lack of robot autonomy by helping it when needed. In this paper,
      the authors propose human-robot integration as a mechanism to augment/improve the
      robot autonomy in daily scenarios. Through the human-robot-integration concept,
      the authors take a further step in the typical human-robot relation, since they
      consider her/him as a constituent part of the human-robot system, which takes
      full advantage of the sum of their abilities. In order to materialize this human
      integration into the system, they present a control architecture, called
      architecture for human-robot integration, which enables her/him from a high
      decisional level, i.e., deliberating a plan, to a physical low level, i.e.,
      opening a door. The presented control architecture has been implemented to test
      the human-robot integration on a real robotic application. In particular, several
      real experiences have been conducted on a robotic wheelchair aimed to provide
      mobility to elderly people.

PMID- 17036813
TI  - Chemical plume source localization.
AB  - This paper addresses the problem of estimating a likelihood map for the location
      of the source of a chemical plume using an autonomous vehicle as a sensor probe
      in a fluid flow. The fluid flow is assumed to have a high Reynolds number.
      Therefore, the dispersion of the chemical is dominated by turbulence, resulting
      in an intermittent chemical signal. The vehicle is capable of detecting above
      threshold chemical concentration and sensing the fluid flow velocity at the
      vehicle location. This paper reviews instances of biological plume tracing and
      reviews previous strategies for a vehicle-based plume tracing. The main
      contribution is a new source-likelihood mapping approach based on Bayesian
      inference methods. Using this Bayesian methodology, the source-likelihood map is
      propagated through time and updated in response to both detection and
      nondetection events. Examples are included that use data from in-water testing to
      compare the mapping approach derived herein with the map derived using a
      previously existing technique.

PMID- 17036814
TI  - Recursive camera-motion estimation with the trifocal tensor.
AB  - In this paper, an innovative extended Kalman filter (EKF) algorithm for pose
      tracking using the trifocal tensor is proposed. In the EKF, a constant-velocity
      motion model is used as the dynamic system, and the trifocal-tensor constraint is
      incorporated into the measurement model. The proposed method has the advantages
      of those structure- and-motion-based approaches in that the pose sequence can be
      computed with no prior information on the scene structure. It also has the
      strengths of those model-based algorithms in which no updating of the three
      dimensional (3-D) structure is necessary in the computation. This results in a
      stable, accurate, and efficient algorithm. Experimental results show that the
      proposed approach outperformed other existing EKFs that tackle the same problem.
      An extension to the pose-tracking algorithm has been made to demonstrate the
      application of the trifocal constraint to fast recursive 3-D structure recovery.

PMID- 17036815
TI  - Dynamic calibration of pan-tilt-zoom cameras for traffic monitoring.
AB  - Pan-tilt-zoom (PTZ) cameras have been widely used in recent years for monitoring
      and surveillance applications. These cameras provide flexible view selection as
      well as a wider observation range. This makes them suitable for vision-based
      traffic monitoring and enforcement systems. To employ PTZ cameras for image
      measurement applications, one first needs to calibrate the camera to obtain
      meaningful results. For instance, the accuracy of estimating vehicle speed
      depends on the accuracy of camera calibration and that of vehicle tracking
      results. This paper presents a novel calibration method for a PTZ camera
      overlooking a traffic scene. The proposed approach requires no manual operation
      to select the positions of special features. It automatically uses a set of
      parallel lane markings and the lane width to compute the camera parameters,
      namely, focal length, tilt angle, and pan angle. Image processing procedures have
      been developed for automatically finding parallel lane markings. Interesting
      experimental results are presented to validate the robustness and accuracy of the
      proposed method.

PMID- 17036816
TI  - New pose-detection method for self-calibrated cameras based on parallel lines and
      its application in visual control system.
AB  - In this paper, a new method is proposed to detect the pose of an object with two
      cameras. First, the intrinsic parameters of the cameras are self-calibrated with
      two pairs of parallel lines that are orthogonal. Then, the poses of the cameras
      relative to the parallel lines are deduced, and the rotational transformation
      between the two cameras is calculated. With the intrinsic parameters and the
      relative pose of the two cameras, a method is proposed to obtain the poses of a
      line, plane, and rigid object. Furthermore, a new visual-control method is
      developed using a pose detection rather than a three-dimensional reconstruction.
      Experiments are conducted to verify the effectiveness of the proposed method.

PMID- 17036817
TI  - Combining genetic algorithms and Lyapunov-based adaptation for online design of
      fuzzy controllers.
AB  - This paper proposes a hybrid approach for the design of adaptive fuzzy
      controllers (FCs) in which two learning algorithms with different characteristics
      are merged together to obtain an improved method. The approach combines a genetic
      algorithm (GA), devised to optimize all the configuration parameters of the FC,
      including the number of membership functions and rules, and a Lyapunov-based
      adaptation law performing a local tuning of the output singletons of the
      controller, and guaranteeing the stability of each new controller investigated by
      the GA. The effectiveness of the proposed method is confirmed using both
      numerical simulations on a known case study and experiments on a nonlinear
      hardware benchmark.

PMID- 17036818
TI  - A vertical-energy-thresholding procedure for data reduction with multiple complex
      curves.
AB  - Due to the development of sensing and computer technology, measurements of many
      process variables are available in current manufacturing processes. It is very
      challenging, however, to process a large amount of information in a limited time
      in order to make decisions about the health of the processes and products. This
      paper develops a "preprocessing" procedure for multiple sets of complicated
      functional data in order to reduce the data size for supporting timely decision
      analyses. The data type studied has been used for fault detection, root-cause
      analysis, and quality improvement in such engineering applications as automobile
      and semiconductor manufacturing and nanomachining processes. The proposed
      vertical-energy-thresholding (VET) procedure balances the reconstruction error
      against data-reduction efficiency so that it is effective in capturing key
      patterns in the multiple data signals. The selected wavelet coefficients are
      treated as the "reduced-size" data in subsequent analyses for decision making.
      This enhances the ability of the existing statistical and machine-learning
      procedures to handle high-dimensional functional data. A few real-life examples
      demonstrate the effectiveness of our proposed procedure compared to several ad
      hoc techniques extended from single-curve-based data modeling and denoising
      procedures.

PMID- 17036819
TI  - Multiscale classification using nearest neighbor density estimates.
AB  - Density estimates based on k-nearest neighbors have useful applications in
      nonparametric discriminant analysis. In classification problems, optimal values
      of k are usually estimated by minimizing the cross-validated misclassification
      rates. However, these cross-validation techniques allow only one value of k for
      each population density estimate, while in a classification problem, the optimum
      value of k for a class may also depend on its competing population densities.
      Further, it is computationally difficult to minimize the cross-validated error
      rate when there are several competing populations. Moreover, in addition to
      depending on the entire training data set, a good choice of k should also depend
      on the specific observation to be classified. Therefore, instead of using a
      single value of k for each population density estimate, it is more useful in
      practice to consider the results for multiple values of k to arrive at the final
      decision. This paper presents one such approach along with a graphical device,
      which gives more information about classification results for various choices of
      k and the related statistical uncertainties present there. The utility of this
      proposed methodology has been illustrated using some benchmark data sets.

PMID- 17036820
TI  - Bayesian model averaging of naive Bayes for clustering.
AB  - This paper considers a Bayesian model-averaging (MA) approach to learn an
      unsupervised naive Bayes classification model. By using the expectation model
      averaging (EMA) algorithm, which is proposed in this paper, a unique naive Bayes
      model that approximates an MA over selective naive Bayes structures is obtained.
      This algorithm allows to obtain the parameters for the approximate MA clustering
      model in the same time complexity needed to learn the maximum-likelihood model
      with the expectation-maximization algorithm. On the other hand, the proposed
      method can also be regarded as an approach to an unsupervised feature subset
      selection due to the fact that the model obtained by the EMA algorithm
      incorporates information on how dependent every predictive variable is on the
      cluster variable.

PMID- 17036821
TI  - Robustly stable adaptive control of a tandem of master-slave robotic manipulators
      with force reflection by using a multiestimation scheme.
AB  - The problem of controlling a tandem of robotic manipulators composing a
      teleoperation system with force reflection is addressed in this paper. The final
      objective of this paper is twofold: 1) to design a robust control law capable of
      ensuring closed-loop stability for robots with uncertainties and 2) to use the so
      obtained control law to improve the tracking of each robot to its corresponding
      reference model in comparison with previously existing controllers when the slave
      is interacting with the obstacle. In this way, a multiestimation-based adaptive
      controller is proposed. Thus, the master robot is able to follow more accurately
      the constrained motion defined by the slave when interacting with an obstacle
      than when a single-estimation-based controller is used, improving the
      transparency property of the teleoperation scheme. The closed-loop stability is
      guaranteed if a minimum residence time, which might be updated online when
      unknown, between different controller parameterizations is respected.
      Furthermore, the analysis of the teleoperation and stability capabilities of the
      overall scheme is carried out. Finally, some simulation examples showing the
      working of the multiestimation scheme complete this paper.

PMID- 17036822
TI  - FCMAC-BYY: fuzzy CMAC using Bayesian Ying-Yang learning.
AB  - As an associative memory neural network model, the cerebellar model articulation
      controller (CMAC) has attractive properties of fast learning and simple
      computation, but its rigid structure makes it difficult to approximate certain
      functions. This research attempts to construct a novel neural fuzzy CMAC, in
      which Bayesian Ying-Yang (BYY) learning is introduced to determine the optimal
      fuzzy sets, and a truth-value restriction inference scheme is subsequently
      employed to derive the truth values of the rule weights of implication rules. The
      BYY is motivated from the famous Chinese ancient Ying-Yang philosophy: everything
      in the universe can be viewed as a product of a constant conflict between
      opposites-Ying and Yang, a perfect status is reached when Ying and Yang achieve
      harmony. The proposed fuzzy CMAC (FCMAC)-BYY enjoys the following advantages.
      First, it has a higher generalization ability because the fuzzy rule sets are
      systematically optimized by BYY; second, it reduces the memory requirement of the
      network by a significant degree as compared to the original CMAC; and third, it
      provides an intuitive fuzzy logic reasoning and has clear semantic meanings. The
      experimental results on some benchmark datasets show that the proposed FCMAC-BYY
      outperforms the existing representative techniques in the research literature.

PMID- 17036823
TI  - Globally asymptotic stability of a class of neutral-type neural networks with
      delays.
AB  - Several stability conditions for a class of systems with retarded-type delays are
      presented in the literature. However, no results have yet been presented for
      neural networks with neutral-type delays. Accordingly, this correspondence
      investigates the globally asymptotic stability of a class of neutral-type neural
      networks with delays. This class of systems includes Hopfield neural networks,
      cellular neural networks, and Cohen-Grossberg neural networks. Based on the
      Lyapunov stability method, two delay-independent sufficient stability conditions
      are derived. These stability conditions are easily checked and can be derived
      from the connection matrix and the network parameters without the requirement for
      any assumptions regarding the symmetry of the interconnections. Two illustrative
      examples are presented to demonstrate the validity of the proposed stability
      criteria.

PMID- 17036824
TI  - Stochastic automata-based estimators for adaptively compressing files with
      nonstationary distributions.
AB  - This correspondence shows that learning automata techniques, which have been
      useful in developing weak estimators, can be applied to data compression
      applications in which the data distributions are nonstationary. The adaptive
      coding scheme utilizes stochastic learning-based weak estimation techniques to
      adaptively update the probabilities of the source symbols, and this is done
      without resorting to either maximum likelihood, Bayesian, or sliding-window
      methods. The authors have incorporated the estimator in the adaptive Fano coding
      scheme and in an adaptive entropy-based scheme that "resembles" the well-known
      arithmetic coding. The empirical results obtained for both of these adaptive
      methods are obtained on real-life files that possess a fair degree of
      nonstationarity. From these results, it can be seen that the proposed schemes
      compress nearly 10% more than their respective adaptive methods that use maximum
      likelihood estimator-based estimates.

PMID- 17036825
TI  - Analysis of brute-force break-ins of a palmprint authentication system.
AB  - Biometric authentication systems are widely applied because they offer inherent
      advantages over classical knowledge-based and token-based personal-identification
      approaches. This has led to the development of products using palmprints as
      biometric traits and their use in several real applications. However, as
      biometric systems are vulnerable to replay, database, and brute-force attacks,
      such potential attacks must be analyzed before biometric systems are massively
      deployed in security systems. This correspondence proposes a projected
      multinomial distribution for studying the probability of successfully using brute
      force attacks to break into a palmprint system. To validate the proposed model,
      we have conducted a simulation. Its results demonstrate that the proposed model
      can accurately estimate the probability. The proposed model indicates that it is
      computationally infeasible to break into the palmprint system using brute-force
      attacks.

PMID- 17036826
TI  - Comments on "Dynamical optimal training for interval type-2 fuzzy neural network
      (T2FNN)".
AB  - In this comment, it will be shown that the backpropagation (BP) equations by Wang
      et al. are not correct. These BP equations were used to tune the parameters of
      the antecedent type-2 membership functions as well as the consequent part of the
      interval type-2 fuzzy neural networks (T2FNNs). These incorrect equations would
      have led to erroneous results, and hence this might affect the comparisons and
      findings presented by Wang et al. This comment will highlight the correct BP
      tuning equations for the T2FNN.

PMID- 17036828
TI  - Twenty-five years of AIDS.

PMID- 17036827
TI  - Comments on "A modified reachability tree approach to analysis of unbounded Petri
      nets".
AB  - The above paper introduced the construction of a modified reachability tree (MRT)
      for (unbounded) Petri nets and its application to reachability, liveness, and
      deadlock analysis. This note shows via a counterexample that some of the MRT
      properties claimed in the above paper are incorrect.

PMID- 17036829
TI  - Off the record.
AB  - Clinical dental records fulfil a variety of functions. Whilst there is no
      standard data set for dental records, it is essential that these are
      contemporaneous--that is, they are 'recorded at the time' A good written record
      should contain details of the patient's identification data, medical and dental
      history, clinical examination, diagnosis, treatment plan, reference to consent,
      and progress notes. This paper covers these aspects in detail, and provides
      information on how long records should be stored, and who may access clinical
      records. CLINICAL RELEVANCE: The recording of contemporaneous patient/treatment
      information is central to treatment planning and good patient care.

PMID- 17036830
TI  - Zirconia-based all-ceramic crowns and bridges: three case reports.
AB  - The search for a clinically viable all-ceramic bridge framework has been
      monotonous. Until recently, few materials appear to have the necessary physical
      and aesthetic properties. However, the development of yttrium tetragonal zirconia
      polycrystals, and its adoption for use in dentistry by CAD CAM technology, may
      hold promise as a crown and bridge framework, this being considered suitable for
      single and multiple units. However, to date, no long-term clinical studies have
      been reported. This paper describes three cases in which zirconia frameworks were
      used in crowns and bridges. CLINICAL RELEVANCE: For the patient wishing to
      receive a non-metal crown or bridge, novel zirconia-based systems hold promise.

PMID- 17036831
TI  - Common facial fractures: 2. management.
AB  - This, the second of three articles, highlights the management of facial fractures
      and the GDP's role in this. CLINICAL RELEVANCE: For patients who present to
      dental practice with facial fractures, it is important that the dentist is able
      to inform the patient of his/her likely management in hospital.

PMID- 17036832
TI  - Vital tooth bleaching in dental practice: 3. Biological, dental and legal issues.
AB  - The final section of this series examines both the evidence for the safety of
      external bleaching with hydrogen peroxide and related products and the legal
      position in the UK with regard to their sale and use in general dental practice.
      Potential side-effects are examined, including biological effects and dental
      effects, with a review of the current evidence. The EU Cosmetics and Medical
      Device Directive are both described and their impact on the provision of tooth
      bleaching in the UK is explained. The legal position in the UK renders the sale
      and supply of solutions containing >0.1% peroxide illegal, and practitioners must
      be aware of the underlying legislation and the basis upon which a prosecution may
      be pursued. CLINICAL RELEVANCE: Clinicians considering using hydrogen peroxide
      products must be aware of the safety issues surrounding their use and be able to
      explain to patients the nature of the risk and also the likelihood of any given
      patient experiencing them.

PMID- 17036833
TI  - Allergic contact stomatitis from colophony.
AB  - Colophony is an ubiquitous contact sensitizer which may be present in dental
      materials, such as periodontal dressings, impression materials, cements, fix
      adhesives and varnishes. Exposure to a sensitizer in a hypersensitive person may
      initiate an allergic contact dermatitis/stomatitis. This usually occurs after
      direct skin/mucosa contact with the sensitizer. This paper reports the case of a
      colophony hypersensitive male who developed contact stomatitis after dental
      treatment with a colophony-containing product. CLINICAL RELEVANCE: Sensitizing
      colophony is present in Duraphat 2.26%F varnish, a fluoride varnish used all over
      the world. A case of hypersensitivity to Duraphat 2.26%F varnish is presented in
      a patient who, at the initial visit, indicated only an allergy to sticking
      plasters.

PMID- 17036834
TI  - Aspects of human disease.
AB  - This series outlines, briefly, the clinical presentation, diagnosis and
      management of the 31 chronic medical problems which are most common and important
      in the developed countries, but space also precludes coverage of acute infections
      and most malignant disease.

PMID- 17036835
TI  - Physical signs for the general dental practitioner. Melkersson-Rosenthal
      syndrome.

PMID- 17036836
TI  - Watershed issues associated with Clostridium botulinum: a literature review.
AB  - Botulism the disease, the related organism (Clostridium botulinum) and toxin have
      gained renewed attention in these times of heightened homeland security and
      bioterrorism preparedness. Since C. botulinum is ubiquitous in nature, botulism
      outbreaks resulting from environmental exposure can be of concern to watershed
      managers and drinking water utilities. This paper reviews aspects of naturally
      occurring C. botulinum in light of concerns for source water watersheds.
      Information regarding sources and occurrence of botulism, C. botulinum and
      botulism toxins are discussed. Ecology and physiology of environmental C.
      botulinum and cycles of disease are reviewed. Finally, the effectiveness of water
      treatment and disinfection measures is discussed.

PMID- 17036837
TI  - Abundance of pathogenic Escherichia coli, Salmonella typhimurium and Vibrio
      cholerae in Nkonkobe drinking water sources.
AB  - In order to study the prevalence of enteric pathogens capable of causing
      infection and disease in the rural communities of Nkonkobe, bacterial isolates
      were collected from several surface water and groundwater sources used by the
      community for their daily water needs. By making use of selective culture media
      and the 20E API kit, presumptive Escherichia coli, Salmonella spp. and Vibrio
      cholerae isolates were obtained and then analysed by polymerase chain reaction
      assays (PCR). The PCR successfully amplified from water samples a fragment of E.
      coli uidA gene that codes for beta-D-glucuronidase which is a highly specific
      characteristic of enteropathogenic E. coli, enterotoxigenic E. coli and entero
      invasive E. coli. The PCR also amplified the epsM gene from water samples
      containing toxigenic V. cholerae. Although E. coli was mostly detected in
      groundwater sources, toxigenic V. cholerae was detected in both surface and
      groundwater sources. There was a possibility of Salmonella typhimurium in Ngqele
      and Dyamala borehole water samples. The presence of these pathogenic bacteria in
      the above drinking water sources may pose a serious health risk to consumers.

PMID- 17036838
TI  - Determination of protection zones for Dutch groundwater wells against virus
      contamination--uncertainty and sensitivity analysis.
AB  - Protection zones of shallow unconfined aquifers in The Netherlands were
      calculated that allow protection against virus contamination to the level that
      the infection risk of 10(-4) per person per year is not exceeded with a 95%
      certainty. An uncertainty and a sensitivity analysis of the calculated protection
      zones were included. It was concluded that protection zones of 1 to 2 years
      travel time (206-418 m) are needed (6 to 12 times the currently applied travel
      time of 60 days). This will lead to enlargement of protection zones, encompassing
      110 unconfined groundwater well systems that produce 3 x 10(8) m3 y(-1) of
      drinking water (38% of total Dutch production from groundwater). A smaller
      protection zone is possible if it can be shown that an aquifer has properties
      that lead to greater reduction of virus contamination, like more attachment.
      Deeper aquifers beneath aquitards of at least 2 years of vertical travel time are
      adequately protected because vertical flow in the aquitards is only 0.7 m per
      year. The most sensitive parameters are virus attachment and inactivation. The
      next most sensitive parameters are grain size of the sand, abstraction rate of
      groundwater, virus concentrations in raw sewage and consumption of unboiled
      drinking water. Research is recommended on additional protection by attachment
      and under unsaturated conditions.

PMID- 17036840
TI  - Low risk for helminth infection in wastewater-fed rice cultivation in Vietnam.
AB  - This study was done to assess the risk of helminth infection in association with
      wastewater-fed rice cultivation in an agricultural setting of Nam Dinh city,
      Vietnam. In a cross sectional survey data were collected for 202 households in a
      commune where wastewater was used for irrigation and for 201 households in a
      commune that used river water. Parasitological examination was conducted on
      single stool samples obtained from 1,088 individuals aged -15 years from the
      households. The irrigation water used in both communes was enumerated for
      helminth eggs and thermotolerant coliforms. The prevalence of infection with
      Ascaris spp., Trichuris spp., and hookworm was 42.2%, 19.9% and 10.5%
      respectively, with an overall prevalence of infection with any helminth of 53.4%.
      Surprisingly, the prevalence of infection with Ascaris and Trichuris was lower
      among people exposed to wastewater (containing 40-200 helminth eggs/l and 10(4)
      thermotolerant coliforms/100 ml) compared to people exposed to river water that
      contained lower worm egg and bacterial numbers. Poor sanitation and hygiene
      practices and not using protective measures were important independent risk
      factors for helminth infection. For hookworm infection, no significant difference
      was observed between the wastewater exposed and unexposed groups. Children living
      in the wastewater use area had a significantly better nutritional status than
      those in the area using river water. This suggests a generally higher welfare
      level of the wastewater use area. In conclusion, this study showed no evidence
      that rice cultivation with wastewater poses a risk for helminth infection. More
      detailed studies are needed on the reduction of fecal indicators and helminth
      eggs in peri-urban wastewater-irrigated rice culture systems and on the relative
      importance of wastewater irrigation compared to other risk factors for human
      helminth infection such as poor sanitation and poverty.

PMID- 17036839
TI  - Seasonal persistence and population characteristics of Escherichia coli and
      enterococci in deep backshore sand of two freshwater beaches.
AB  - We studied the shoreward and seasonal distribution of E. coil and enterococci in
      sand (at the water table) at two southern Lake Michigan beaches-Dunbar and West
      Beach (in Indiana). Deep, backshore sand (approximately 20 m inland) was
      regularly sampled for 15 months during 2002-2003. E. coli counts were not
      significantly different in samples taken at 5-m intervals from 0-40 m inland (P =
      0.25). Neither E. coli nor enterococci mean counts showed any correlation or
      differences between the two beaches studied. In laboratory experiments, E. coli
      readily grew in sand supplemented with lake plankton, suggesting that in situ E.
      coil growth may occur when temperature and natural organic sources are adequate.
      Of the 114 sand enterococci isolates tested, positive species identification was
      obtained for only 52 (46%), with E. faecium representing the most dominant
      species (92%). Genetic characterization by ribotyping revealed no distinct
      genotypic pattern (s) for E. coli, suggesting that the sand population was rather
      a mixture of numerous strains (genotypes). These findings indicate that E. coli
      and enterococci can occur and persist for extended periods in backshore sand at
      the groundwater table. Although this study was limited to two beaches of southern
      Lake Michigan, similar findings can be expected at other temperate freshwater
      beaches. The long-term persistence of these bacteria, perhaps independent of
      pollution events, complicates their use as indicator organisms. Further,
      backshore sand at the water table may act as a reservoir for these bacteria and
      potentially for human pathogens.

PMID- 17036841
TI  - Monitoring source and domestic water quality in parallel with sanitary risk
      identification in northern Mozambique to prioritise protection interventions.
AB  - Microbiological water quality monitoring in Niassa province, Northern Mozambique,
      shows groundwater is not, in general, grossly contaminated though contamination
      levels are strongly linked to season and to risks observable at the wellhead,
      especially risks dealing with wellhead hygiene and maintenance. Diarrhea
      incidence, in general, is greatest in the rainy season suggesting poor wellhead
      protection as a potential mechanism for well contamination. Comparison of source
      water and stored water in the home shows that significant deterioration in source
      water quality can occur once transport and storage in the home is undertaken but
      that this deterioration is also related to the quality of the source water. This
      study shows that a structured approach to water quality monitoring, with targeted
      observations and an examination of the relationships between risk and water
      quality, is important to identify the priority interventions to be undertaken.

PMID- 17036842
TI  - Population similarity of enterococci and Escherichia coil in surface waters: A
      predictive tool to trace the sources of fecal contamination.
AB  - A biochemical fingerprinting method (the PhPlate system) was used to compare
      similarities between Escherichia coli and enterococci populations from surface
      water samples with those found in different animal species during the wet and the
      dry seasons in order to predict the dominant source(s) of fecal contamination in
      a local creek. A significant increase in the number and diversity of enterococci
      was observed in the creek during the wet season. Enterococci population from
      water samples also showed a higher population similarity with animal species than
      did E. coli. A higher population similarity was found between both indicator
      bacteria and animal species during the wet season with highest population
      similarities found in dogs, horses, cows and kangaroos. In contrast, a low
      population similarity was found for both fecal indicator bacteria from humans
      with water samples during the wet and the dry seasons, indicating that humans are
      not a major source of contamination in the studied creek. The results also
      indicate that the population similarity analysis of enterococci population has an
      advantage over E. coli in tracing the possible source(s) of contamination in the
      studied creek and that population similarity analysis as used in this study can
      be used to predict the source(s) of fecal contamination in surface waters.

PMID- 17036843
TI  - Diffuse pollution in Oxford (Ohio, USA) watershed and performance of 'street
      sweeping' as a 'best management practice' (BMP).
AB  - Experimental results are described to evaluate the diffuse pollution profile
      according to land use in the catchments and street sweeping as a best management
      practice (BMP). We studied the variation of pollutant concentrations in outfalls
      discharging runoff from residential, commercial and high-traffic areas and in
      street sweeping. Pollution profiles varied with the land use in the catchments
      and seasons along with other factors such as rainfall intensity, construction
      works and street maintenance. Microbial indicator organisms were relatively high
      in all three outfalls. Heavy metal concentrations were low with lead (Pb) as the
      predominant heavy metal. The organic and solid contents were low but non
      degradable and persistent. Relatively high quantities of pollutants were found in
      street sweeps in all catchments suggesting street sweeping as an effective
      measure to control diffuse pollution. Regular and frequent sweeping is important
      as a BMP.

PMID- 17036844
TI  - The health effects of flooding: Social research results from England and Wales.
AB  - This paper presents interview survey data by social scientists using established
      health measures on the health effects of flooding for residents in 30 locations
      in England and Wales. Firstly, it examines the extent to which flooded residents
      reported suffering physical and psychological health effects during and after the
      event. Secondly, it explores the issue of whether these effects were long-lasting
      by comparisons with the general population and with those at risk but not
      flooded. In the study, about two thirds of the flood victims were found to have
      scores on the General Health Questionnaire-12 scale indicative of mental health
      problems (scores of 4+) at their worst time after flooding. The evidence of the
      study also suggests that some flood victims suffered long term mental health
      effects as a result of their experience of flooding. The study examines the
      influence of a wide range of factors: characteristics of the flood event, types
      of property, and socio-demographic and the intervening factors such as the extent
      of family or community support that may explain the health effects of flooding.
      It finds that a complex set of social and other factors are involved and that
      some factors susceptible to human intervention such as having adequate flood
      insurance cover are important factors in the stress experienced by flood victims.

PMID- 17036845
TI  - Identification by microarray of a common pattern of gene expression in intact
      intestine and cultured intestinal cells exposed to virulent Aeromonas hydrophila
      isolates.
AB  - The genus Aeromonas comprises known virulent and avirulent isolates and has been
      implicated in waterborne disease. A common infection model of human
      gastroenteritis associated with A. hydrophila uses neonatal mice. The goal of
      this research was to evaluate whether a murine small intestinal cell line could
      provide comparable results to the gene expression changes in the neonatal mouse
      model. Changes in mRNA expression in host cell cultures and intestinal tissues
      were measured after exposure to virulent Aeromonas hydrophila strains. A.
      hydrophila caused the up-regulation of more than 200 genes in neonates and over
      50 genes in cell culture. Twenty-six genes were found to be in common between the
      two models, of which the majority are associated with the innate immune response.

PMID- 17036846
TI  - Effects of temperature and sand on E. coil survival in a northern lake water
      microcosm.
AB  - A concern for public health officials is the presence of Escherichia coli (E.
      coli), an indicator of fecal contamination, in monitoring recreational waters.
      While E. coli is unlikely to cause disease in humans, its presence may indicate
      other more pathogenic microorganisms. Many factors can lead to changes in the
      survival of E. coli outside of the animal intestine and may affect the
      probability of colonizing a new host. Survival of bacteria in recreational water
      has been linked to water temperature, and most recently to the presence of sand
      on the beach. This project looked at the survival of an environmental E. coli
      isolate in lake water. Lake water microcosms were placed at 4, 10, 14, or 25
      degrees C for up to 36 d and an enzyme-substrate test (Colisure, IDEXX Corp.) was
      used to determine the most probable number (MPN) of E. coli/100 ml water. E. coli
      numbers at all temperatures declined over the duration of the experiment. The
      decline was most pronounced at 14 degrees C and was slowest at 4 degrees C. The
      presence of sand in the microcosm increased the time that E. coli survived,
      regardless of temperature. From a beach management standpoint, these findings
      indicate that E.coli may persist in the environment in cooler water longer than
      in the warmer water encountered in late summer.

PMID- 17036847
TI  - Effect of soil depth and texture on fecal bacteria removal from septic effluents.
AB  - This study evaluated the effectiveness of soils with different texture and depth
      to treat fecal bacteria eluted from a house-hold septic effluent. The assessments
      were accomplished by leaching undisturbed soil monoliths of 30, 45, and 60cm
      thickness and 25cm in diameter, representing the four different textural groups
      and hydraulic loadings recommended by the Kentucky Health Department, with
      domestic wastewater effluent collected regularly from a house-hold septic system.
      Eluent concentrations were monitored daily over a 15 day period for fecal
      coliform and fecal streptococci concentrations. The results of the study indicate
      an alarming frequency of failure to comply with United States Environmental
      Protection Agency (USEPA) criteria for depth to groundwater, when using a 30 cm
      vertical separation distance between the bottom of the drain-field and a limiting
      soil interface. The treatment performance was especially poor in coarse-textured
      soils. Although biomat development over time is expected to improve treatment,
      the high influent levels of fecal bacteria pose great concerns for surface and
      groundwater contamination. Fine-textured soils generally provided better
      treatment efficiency and more consistent compliance with EPA standards. Treatment
      efficiency and compliance usually improved with increasing soil depth, with the
      60cm thickness providing the most consistent performance and compliance with
      maximum discharge limit (MDL) requirements. The findings of this study document a
      general inadequacy of the 30cm vertical separation distance to provide effective
      treatment of septic effluents in Kentucky soils, particularly in coarse-textured
      soils. Considering that increasing the soil depth thickness may be impractical in
      many marginal soils, complementary or alternative treatment technologies should
      be adopted to improve treatment efficiency and prevent further deterioration of
      the quality of water resources.

PMID- 17036848
TI  - A week we don't want to forget: lessons learned from Tulane.
AB  - By the time I walked into the conference call at about 7 a.m. on Tuesday, August
      30, HCA's Tulane hospital was surrounded by between four and six feet of water,
      depending on the side of the building. The water was slowly rising. An estimated
      1,300 people were trapped at Tulane Hospital. No CEO has ever had as much reason
      to be proud of his company as I did during the next few days. We safely evacuated
      Tulane's patients, staff members, and family members, coordinating more than 200
      helicopter sorties to and from Tulane in the process. We transferred every
      patient to a waiting hospital and took nearly every staff and family member to an
      HCA-run shelter in Lafayette, Louisiana, where they were bathed, fed, inoculated,
      given shelter, given access to prepaid cellular phones, and sent where they
      needed to go. This, I believe, was one of HCA's greatest hours, but we also
      learned many lessons from the catastrophic event. Although we hope and pray that
      nothing like this ever happens again, the things we learned can be of use to the
      healthcare community at large.

PMID- 17036849
TI  - Hurricane Katrina and the healthcare infrastructure: A focus on disaster
      preparedness, response, and resiliency.
AB  - The aftermath of Hurricane Katrina provides a window of opportunity to address a
      frail and failing healthcare system. Katrina was the rare incident that disrupted
      the external systems supplying hospitals with key services and resources needed
      for the organizations to function; increased the number of patients, both present
      and expected, that required medical care; and affected directly the physical
      plants of the hospitals, challenging their functionality. Sorting through and
      gleaning useful lessons to increase the resilience of hospitals for this type of
      catastrophic incident will take time and will require system-wide public health
      planning and intervention. In this article, the authors focus on how hospitals
      prepared for, responded to, and coped with Katrina. They also provide a brief
      overview of the current situation and the healthcare crisis confronting hospitals
      and communities in the region affected by Katrina and discuss the impending need
      to develop disaster-resilient medical and healthcare systems. Planning, access to
      adequate resources, networking, effective communication and coordination, and
      training and education of doctors, nurses, technicians, and medical staff are
      essential in the development of a resilient healthcare infrastructure that will
      be able to provide the much needed services to populations affected by future
      disasters.

PMID- 17036850
TI  - Can it get any worse?
AB  - THE TWO FEATURE articles presented in this issue of Frontiers of Health Services
      Management speak to the challenges of Hurricane Katrina. The Tulane experience
      lists a multitude of problems, solutions, and successes, whereas the article by
      Drs. Rodriguez and Aguirre speaks to the impact on the infrastructure following
      the hurricane. In the federal report, "The Federal Response to Hurricane
      Katrina," the White House (2006) has labeled Katrina as "the most destructive
      natural disaster in U.S. history." Dr. E. L. Quarantelli (2006) might call
      Katrina a catastrophe. Regardless of what one calls the event, Hurricane Katrina
      has shown that the challenges leading up to and following a disaster/catastrophe
      will overwhelm everyone. People must understand that they cannot wait for a
      government, any government, to help them. We must be prepared to help ourselves.

PMID- 17036851
TI  - Keeping patients safe when disaster strikes.

PMID- 17036852
TI  - Not for profit hospitals: balancing business and benefit.

PMID- 17036853
TI  - [Subtle skin lesions in the midline as an indication of a neurodermal closing
      defect].
AB  - Three patients, aged 2, 2.5 and 24 years, presented with a skin lesion in the
      median or paramedian area at the nose, in the lumbar region and between the
      shoulders, respectively. The first patient suffered from recurrent infection, the
      skin lesion of the second patient was a coincidental finding, and the third
      patient had cosmetic problems. Although there were no signs of neurological
      deficits, neurodermal closing defects were found by MRI. Two patients underwent
      surgery to prevent infection and neurological complaints in the future. It is
      stressed that even if there are no neurological signs or infections, congenital
      dermal lesions situated in the midline should be considered as possible neural
      tube defects and therefore analysed by MRI. Ifa neurodermal dysraphism is found,
      patients should be referred to a neurosurgical centre. A good clinical assessment
      of the neural lesion, clinical signs and age will determine whether surgical
      resection is indicated to prevent or resolve neurological problems, infections or
      cosmetic complaints.

PMID- 17036854
TI  - [Treatment of patients with the chronic-fatigue syndrome].
AB  - In the last few years, the chronic-fatigue syndrome has been recognised as an
      important health problem. In a recent report, the Health Council of the
      Netherlands suggested that the capacity for treatment be increased. Cognitive
      behavioural therapy and graded exercise training are treatment options of first
      choice. A recently published, uncontrolled evaluation of a Dutch clinical
      rehabilitation programme based partly on these methods proved to be successful.
      Unfortunately, due to the uncontrolled character of the study, it remains unclear
      which elements in the treatment were responsible for the success. Which patients
      should be included in a costly clinical rehabilitation programme also remains
      unclear. More in general, there is room for empirical studies of treatment
      allocation, not in the least because of the frequently occurring comorbidity.
      Good progress has been made in the treatment of the chronic-fatigue syndrome, but
      we are still far removed from evidence-based, stepped care, treatment programmes.

PMID- 17036855
TI  - [Health effects of fish oil and fish oil supplements: consumption advice
      sustained].
AB  - Omega-3 fatty acids are thought to have beneficial effects on atherosclerosis.
      Recently, the results ofa systematic review on the health effects of omega-3
      fatty acids were published. The risk of cardiovascular death in subjects
      randomised to taking omega-3 fats was not significantly decreased: relative risk
      = 0.87 (95% CI: 0.73-1.03). In a 2004 Cochrane review, the same authors concluded
      that there was a significant beneficial effect on total mortality, combined
      cardiovascular endpoints and cancer. Inclusion of the recent 'Diet and
      reinfarction trial' (DART-2-trial) had a decisive negative effect on the results
      of the recent meta-analysis. Excluding this study resulted in a relative risk of
      cardiovascular death of 0.83 (95% CI: 0.75-0.91). Since the DART-2 study had
      methodological shortcomings, it still appears that recommending sufficient intake
      of omega-3 fatty acids is justifiable, preferably by eating fish but ifnecessary
      by using fish oil supplements, especially for patients at high risk of
      cardiovascular disease.

PMID- 17036856
TI  - [Hypospadias and congenital curvature of the penis in children and their surgical
      treatment].
AB  - Hypospadias is a congenital defect of the penis in which the urethral orifice is
      located on the ventral aspect of the glans penis or, more proximally, on the
      shaft or scrotum. Some type of hypospadias occurs in approximately 1 in 200 boys.
      The defect can be minimal or so severe that the sex of the newborn is difficult
      to determine. Many boys with hypospadias also have a congenital curvature of the
      penis that needs correction. Corrective surgery is done preferably between the
      ages of 6 and 12 months. The aim of surgery is to obtain a functionally and
      cosmetically normal penis while limiting the psychological burden on the child as
      much as possible. The common surgical procedures include: meatal advancement and
      glanuloplasty (MAGPI), the tubularised incised plate (TIP) technique according to
      Snodgrass, and vascularised foreskin flap-plasty. Urethral surgery for
      hypospadias is accompanied by a relatively high number of complications and
      should therefore be carried out by surgeons with sufficient experience.

PMID- 17036857
TI  - [Clinical reasoning and decision-making in practice. A man with inexplicable
      joint pain and subsequent poor clinical condition].
AB  - A 52-year-old man presented with polyarthritis and was negative for rheumatoid
      factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of
      first choice in rheumatoid arthritis. The arthritis disappeared, but the patient
      developed fever, progressive dyspnoea, appetite loss and weight loss. Upon
      hospital admission his medication was stopped and community-acquired pneumonia
      was diagnosed. The fever persisted despite antibiotic treatment. The tentative
      diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus,
      based on the change in clinical condition that could not be explained by
      polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was
      treated with high-dose steroids and azathioprine and remained in remission for
      more than 1 year after treatment. The ANA test remained strongly positive,
      whereas anti-dsDNA was no longer detectable. This case stresses the limited value
      of classification criteria for the diagnosis of rheumatoid arthritis. To
      differentiate between rheumatoid arthritis and systemic lupus erythematosus,
      tests for autoantibodies against citrullinated peptides can be used. To
      differentiate between systemic lupus erythematosus and infection, tests for anti
      dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can
      be used.

PMID- 17036858
TI  - [Diagnostic image (292). A man with a pulsatile temporal swelling].
AB  - A 19-year-old man developed a pulsatile swelling in the left temporal area due to
      a false aneurysm of the superficial temporal artery, two weeks after a blunt
      trauma caused by a heading duel during a soccer match.

PMID- 17036859
TI  - [Prevention of allergy is both useful and necessary].
AB  - Refraining from smoking during pregnancy and giving exclusively breast feeding
      for 4-6 months reduce the chance of allergic manifestations during the first 6
      years of life and possibly longer. Hypoallergenic baby foods have a comparable
      effect on food allergy and atopic eczema, but their long-term effects remain
      uncertain. The prevention of allergy is therefore both possible and useful.

PMID- 17036860
TI  - [Allergy prevention is an illusion].
AB  - The recommendation that babies with a familial predisposition for allergic
      diseases be given hypoallergenic baby food is based on studies that were
      insufficiently blinded. The prevention of allergic sensitisation in the long term
      has never been demonstrated. Exposure to allergens is not the determining factor
      in the development of allergic diseases. It is probable that only the mild forms
      of eczema are to a certain extent delayed. For the time being, therefore, the
      prevention of allergy is an illusion.

PMID- 17036861
TI  - [Favourable results of a rehabilitation programme with cognitive behavioural
      therapy and graded physical activity in patients with the chronic-fatigue
      syndrome].
AB  - OBJECTIVE: To determine whether a specific course of interdisciplinary
      rehabilitation might lead to clinically significant changes in fatigue,
      experienced disability and physical function in patients with the chronic-fatigue
      syndrome (CFS). DESIGN: Prospective and uncontrolled. METHOD: 'Het Roessingh', a
      rehabilitation centre in Enschede, the Netherlands, has developed an
      interdisciplinary clinical rehabilitation programme for patients with CFS in
      cooperation with the 'Nijmeegs Kenniscentrum Chronische Vermoeidheid' [Chronic
      Fatigue Knowledge Centre] in Nijmegen, the Netherlands. In this programme,
      physical, mental and social activities are gradually increased on the basis of
      cognitive behavioural principles and graded activity. Of the 127 successive
      persons who enrolled for the therapy during the period from August 2000 to
      December 2004, 99 fulfilled the inclusion criteria; they had a median duration of
      symptoms of 6 years. The results of treatment were evaluated by a measurement
      with the 'Checklist individuele spankracht' [Checklist individual muscle tone]
      before and after treatment and the scores on the 'Patientspecifieke beperkingen'
      [Patient-specific disability] and the Short form-36. The measured data were
      complete in 74 patients. RESULTS: Before rehabilitation, the levels of fatigue,
      disability and distress were high. After treatment, the studied population showed
      significant improvement in fatigue, experienced disability and physical function.
      The magnitude of the improvement was generally 'average'. At the end of
      treatment, 70% of the patients were clinically less fatigued, 68% experienced
      less disability and 55% functioned better physically. In 34% the level of fatigue
      was normalised after treatment, but 9.5% of the patients was more fatigue.
      CONCLUSION: The rehabilitation programme offered for CFS led to significant
      improvements in function and fatigue.

PMID- 17036863
TI  - [Kikuchi's histiocytic necrotising lymphadenitis: a benign disorder--not to be
      confused with malignant lymphoma].
AB  - A 26-year-old woman who later turned out to have the rarely seen histiocytic
      necrotising lymphadenitis of Kikuchi was twice diagnosed incorrectly with
      malignant T-cell lymphoma. She was treated with standard chemotherapy, whereas
      Kikuchi's disease has a self-limiting course. Fear for recurrent lymphoma greatly
      affected the patient's life until the proper diagnosis was ultimately made. This
      occurred after the patient herself had seen in her dossier that the diagnosis
      'Kikuchi's histiocytic lymphadenitis' had been proposed by two pathologists of
      the consulted regional lymphoma board in the past, but had been rejected by the
      board after external consultation.

PMID- 17036862
TI  - [Partial resistance to acenocoumarol and phenprocoumon caused by enzyme
      polymorphism].
AB  - A 78-year-old man was treated with coumarin derivatives following myocardial
      infarction. The international normalised ratio was not increased by using
      standard loading doses and dose adjustments for acenocoumarol and phenprocoumon.
      The desired level of anticoagulation was achieved with a high dosage of
      phenprocoumon (18-21 mg daily). This dose was associated with a phenprocoumon
      serum concentration that was ten times higher than the normal therapeutic
      concentration. The serum concentration of vitamin K1 was low. After exclusion of
      alternative causes, we concluded that the exceptionally high dose of
      phenprocoumon needed was due to partial resistance to coumarin derivatives.
      Partial resistance is related to a polymorphism of the gene coding for the enzyme
      vitamin K epoxide reductase. The patient was successfully treated with chronic
      high-dose phenprocoumon. Resistance to coumarin derivatives caused by a
      congenital polymorphism in the vitamin K reductase gene is a rare phenomenon.
      Resistance is seldom absolute. The desired anticoagulation effect can be achieved
      with doses that are 10-20 times higher than standard doses. Phenprocoumon is
      advantageous in this situation because it requires fewer tablets than
      acenocoumarol. Determination of serum concentrations of acenocoumarol and
      phenprocoumon can be used to exclude other causes of treatment resistance.

PMID- 17036864
TI  - [Defining trials of medicinal products according to the revised Dutch Medical
      Research in Human Subjects Act (WMO)].
AB  - The revised Dutch Medical Research in Human Subjects Act (WMO), which implements
      the European directive regarding 'good clinical practice in the conduct of
      clinical trials on medicinal products for human use' (2001/20/EC), became
      effective on March 1, 2006. The revision places additional requirements on trials
      of medicinal products. Whether a trial should be regarded as a trial of a
      medicinal product is therefore an important question. The law does not provide
      adequate guidance for the classification of trials in which biological samples
      are collected, e.g. for genomic, proteomic or pharmacokinetic studies, while a
      medicinal product is given for a registered indication. Classifying these types
      of trials as trials of medicinal products does not enhance the safety of the
      participants. Therefore, these studies should not be considered as trials of
      medicinal products to avoid the increased administrative burden required by the
      revised WMO.

PMID- 17036865
TI  - [A 26-year-old cyclist with intermittent claudication].

PMID- 17036866
TI  - The big squeeze. Insurers point to slower growth in premiums in past few years to
      show progress, but providers say they're paying the price.
AB  - While insurers last week were trumpeting the third straight year of slower growth
      in premiums, providers weren't exactly celebrating. That's because of huge
      mergers, which give insurers far more leverage and have led to reimbursements
      being cut back even more. "What's worrying us is that there's a growing segment
      (of insurers) that aren't going to budge an inch, no matter what," says Russ
      Weaver, left.

PMID- 17036867
TI  - Measuring improvement. Performance standards, reporting save lives: NCQA.

PMID- 17036868
TI  - Norwalk's CMS hurdles. Interim head faces Part D, reimbursement woes.

PMID- 17036869
TI  - HRDI settlement near? Agreement likely to include payment concessions.

PMID- 17036870
TI  - Tenet, HealthSouth clear some legal woes.

PMID- 17036871
TI  - CHW settlement ups discounts.

PMID- 17036872
TI  - Low scores, high costs. With waste and inefficiency rife, Americans need more
      than HSAs.

PMID- 17036873
TI  - Foreign exchange. CFOs in the U.K. seek greater collaboration between finance,
      clinical teams as the National Health Service pursues reforms.

PMID- 17036874
TI  - Out through the in door. Our annual Outsourcing Survey shows an uptick in
      clientele as companies work to expand the array of services they offer.

PMID- 17036875
TI  - Largest healthcare financing companies ranked by amount of loans underwritten
      January through August 2006.

PMID- 17036876
TI  - Is local A&E a thing of the past?

PMID- 17036877
TI  - "Ageing Londoners deserve more focused healthcare".

PMID- 17036878
TI  - "We can no longer blame the quality of hospital food for malnutrition in
      hospitals".

PMID- 17036879
TI  - Can nursing ever be stress free?

PMID- 17036880
TI  - Keeping children safe from allergies. Interview by Janis Smy.

PMID- 17036881
TI  - Combating a rising incidence of Legionnaire's disease.
AB  - A statement released last week by the Health Protection Agency highlighted a
      recent increase in the incidence of Legionnaire's disease in England and Wales.
      Although an upsurge in cases is common at this time of year due to people
      returning from holidays abroad, only a small proportion of the recent cases can
      be attributed to foreign travel. Nurses need to be aware of the symptoms and what
      health measures they can take.

PMID- 17036882
TI  - Cricoid pressure.

PMID- 17036883
TI  - Planning to improve the hospital experience for older inpatients.
AB  - It is estimated that by 2031 the number of people aged 65 and over will exceed 15
      million and comprise 23% of the whole population (Central Office of Information,
      2006). This population shift will have dramatic effects on healthcare provision
      and it is essential not only that the services are in place to meet this demand
      but also that nurses have the skills to care for this age group.

PMID- 17036884
TI  - Using audit to change practice for routine glucochecks.
AB  - Glucochecks are commonly used on admission to hospital to pinpoint patients who
      may have diabetes. This summary paper describes two clinical audits assessing
      action following glucocheck results and staff education to improve follow-up. The
      full audit paper can be accessed at nursingtimes.net.

PMID- 17036885
TI  - Clinical decision-making and the nurse consultant role.
AB  - This paper reviews the requirement for expert clinical decision-making in the
      role of nurse consultants. The aim is to gain a better understanding of this role
      by exploring the experiences and views of consultant practitioners. This is a
      summary of the paper: the full version can be accessed at nursingtimes.net.

PMID- 17036886
TI  - Implications of social enterprise for community nursing.
AB  - Scott McAusland outlines the key points of the Queen's Nursing Institute briefing
      paper Social Enterprise and argues that many clinicians need to develop business
      and financial skills to take up social enterprise opportunities.

PMID- 17036887
TI  - Managing infants with pyrexia.
AB  - The management of pyrexia and fever is one of the most common childhood problems
      faced by parents and health professionals, both in hospital and primary
      healthcare settings. Cathy Taylor discusses the advice that should be offered to
      parents. She identifies that the evidence base that supports this advise is
      patchy.

PMID- 17036888
TI  - Pneumococcal vaccine and the new child vaccination schedule.
AB  - A vaccine to protect against pneumococcal infection is now offered to all UK
      infants as part of the primary immunisation schedule. This, together with
      modifications to the schedule for Haemophilus influenzae type b and meningococcal
      C vaccines, represents the latest changes to the routine childhood immunisation
      programme, which came into effect on 4 September. Helen Bedford and Laura Lane
      outline why the pneumococcal vaccine has been introduced and the other changes to
      the immunisation schedule.

PMID- 17036890
TI  - Has the CMP become obsolete?

PMID- 17036889
TI  - An overview of managing anaphylaxis in the community.
AB  - Phil Jevon discusses the management of anaphylaxis in the community and the
      national consensus guidelines on anaphylaxis (Project Team of the Resuscitation
      Council UK, 2005).

PMID- 17036892
TI  - [Dermatitis from the green lawn].

PMID- 17036894
TI  - [Anorexia and bulimia. When food becomes the enemy].

PMID- 17036893
TI  - [Without short acting insulin analogs. Is therapy quality really maintained?
      (interview by Dirk Einecke)].

PMID- 17036895
TI  - [Obesity time bomb. The fantasy land of plenty strikes back].

PMID- 17036896
TI  - [New treatment method for incontinence (interview by Thomas Meissner)].

PMID- 17036897
TI  - [Emergency rescue services cost a lot of money. However, no one pays for quality
      control].

PMID- 17036898
TI  - [Intensified insulin therapy. Is there an alternative to BE count?].

PMID- 17036899
TI  - [Weight loss and recurrent erythema as a puzzle for physicians. Skin
      manifestations came from the heart].

PMID- 17036900
TI  - [Measure your patients blood pressure in all life situations. An elevated blood
      pressure in the office is not hypertension].

PMID- 17036901
TI  - [Blood pressure self measurement (BPSM)].
AB  - Blood pressure self measurement (BPSM) offers advantages over measurements in the
      doctor's office, and may improve the overall management of hypertension. BPSM
      permits the identification of "white-coat hypertension" and "masked
      hypertension". Longitudinal studies are needed to determine the true importance
      of BPSM. Doctors must be aware of the strengths and weaknesses of BPSM and be
      able to provide their patients with information about available devices for self
      measurement, in particular about the accuracy and reliability of the devices they
      are using. Patient training in blood pressure measurement should concentrate on
      classification of blood pressure, blood pressure variability, standardized self
      measurement, interpretation of the readings, and treatment of hypertension.

PMID- 17036902
TI  - [Ambulatory long-term blood pressure measurement].
AB  - Ambulatory 24-hour blood pressure measurement (ABPM) is a highly suitable method
      for detecting nocturnal variations in blood pressure, early morning peaks and
      unusual fluctuations during the course of the day. It enables an unequivocal
      diagnostic work-up as also accurate treatment control. Moreover, the normal
      values are lower than those measured during the occasional visits to the doctor's
      office.

PMID- 17036903
TI  - [Blood pressure measurement during ergometry].
AB  - Blood pressure measurement during ergometry makes it possible to investigate the
      blood pressure behavior during physical effort. It is considered an option for
      the early detection of arterial hypertension, for the reliable investigation of
      the efficacy of antihypertensive therapy also under conditions of effort, and for
      the prognostic assessment of sequelae and cardiovascular events. The method is
      simple and inexpensive, requires little expenditure of time, and produces readily
      reproducible results. The submaximal workload range permits a ready
      differentiation to be made between normotension and hypertension, while at the
      same time, this workload range mimics everyday bodily effort, and, in principle,
      can therefore be employed in all patients.

PMID- 17036904
TI  - [Tilidine-Naloxone sustained-release tablets for chronic pain associated with
      musculoskeletal disease].

PMID- 17036905
TI  - [Diabetes mellitus and frequently associated endocrine diseases].
AB  - The simultaneous occurrence of type 1 or type 2 diabetes with various hormonal
      diseases (e.g. thyroid, adrenal, pituitary disease) is a frequent observation. A
      chronically poorly controlled metabolism can alter the hormone parameters of the
      diabetic. In contrast, an acute loss of metabolic control may be a sign of a
      newly manifesting hormonal disease, and needs always prompt an appropriate
      diagnostic work-up and treatment. In view of the frequency both of diabetes
      mellitus and thyroid disease, a regular check--at least yearly and always in case
      of unclear worsening of diabetic control--of thyroid gland function is mandatory.
      The aim is to provide appropriate treatment, and thus to stabilize the patient's
      metabolic status, as early as possible.

PMID- 17036906
TI  - [Return of African sleeping sickness].
AB  - At present there is a steady rise in African sleeping sickness (trypanosomiasis)
      transmitted by the Tsetse fly, and which if left untreated, is fatal. Thanks to
      more than so years of neglect by research, our therapeutic repertoire is limited
      to medications with a high level of toxicity. Both WHO and international aid
      organizations are pushing hard for the development of new, more efficient drugs
      that can be readily applied in the field.

PMID- 17036907
TI  - [Type 2 diabetes: hypoglycemia risk, weight gain... Will there soon be a new
      alternative to insulin?].

PMID- 17036908
TI  - [Therapy with incretin mimetic exenatide. Soon HbA1c value and weight decrease
      permanently].

PMID- 17036909
TI  - [Ambulatory treatment should soon be more independent. Good new--or bad news?].

PMID- 17036910
TI  - [Reimbursement information is already in process. Despite this public health
      insurance can still reclaim money].

PMID- 17036911
TI  - [What would happen... if the physician were paid according to treatment
      success?].

PMID- 17036912
TI  - Disorders of calcium metabolism.
AB  - Hypocalcaemia not associated with hypoalbuminaemia or 25(OH)-Vitamin D deficiency
      is rare and should be referred to a specialist clinic. 25(OH)-Vitamin D
      deficiency can often be treated safely by GPs, unless it is associated with renal
      impairment and secondary hyperparathyroidism, in which case a nephrology referral
      is required. An endocrine referral is required if deficiency is associated with
      pregnancy, co-existent primary hyperparathyroidism or the patient is receiving
      warfarin. The key role of the GP in managing hypercalcaemia is to distinguish
      between malignant and parathyroid causes in order to make the appropriate
      specialist referral (oncology, endocrine or renal). Severe hypercalcaemia
      (greater than 3.5 mmol/L or hypercalcaemia with dehydration, abdominal pain or
      reduced consciousness is a medical emergency.

PMID- 17036913
TI  - Advising adults with type 1 diabetes.

PMID- 17036914
TI  - How to detect growth disorders.

PMID- 17036915
TI  - Cholesterol management.

PMID- 17036916
TI  - Diagnose and treat hearing loss.

PMID- 17036918
TI  - The MRCGP exam: an overview.

PMID- 17036917
TI  - Manage urinary tract infections.

PMID- 17036919
TI  - A guide to bacterial skin infections.

PMID- 17036920
TI  - Anti-emetics, NSAIDs and opiates in migraine.

PMID- 17036922
TI  - Genetic diversity and linkage disequilibrium in the Polynesian population of Niue
      Island.
AB  - Isolated populations that recently have been derived from small homogeneous
      groups of founders should have low genetic diversity and high levels of linkage
      disequilibrium and should be ideal for mapping ancestral polymorphisms that
      influence complex genetic disease susceptibility. Populations that fulfill these
      criteria have been difficult to identify. We have been looking for Polynesian
      populations with these characteristics, because Polynesians have high rates of
      complex genetic diseases. In Niue Islanders all ancestral female (mitochondrial
      HSVI sequence) and 90.4% of ancestral male (Y-chromosome haplogroup) lineages are
      of Southeast Asian origin. The frequency of European Y-chromosome haplogroups is
      7.2%. The diversities of mitochondrial HSV1 sequences (h = 0.18 +/- 0.05) and Y
      chromosome haplo-groups (h = 0.18 +/- 0.05) are lower than values published for
      any other population. Ten autosomal microsatellites spaced over 5.8 cM show low
      allele numbers in Niue Islanders relative to Europeans (55 vs. 88 total alleles,
      respectively) and a modest reduction in heterozygous loci (0.71 +/- 0.02 vs. 0.78
      +/- 0.02, p = 0.04). The higher linkage disequilibrium (d2) between these loci in
      Niue Islanders relative to Europeans (p = 0.001) is negatively correlated (r = 
      0.47, p = 0.01) with genetic distance. In summary, Niue Islanders are genetically
      isolated and have a homogeneous Southeast Asian ancestry. They have reduced
      autosomal genetic diversity and high levels of linkage disequilibrium that are
      consistent with the influence of genetic drift mechanisms, such as a founder
      effect or bottlenecks. High-powered linkage disequilibrium studies designed to
      map ancestral polymorphisms that influence complex genetic disease susceptibility
      may be feasible in this population.

PMID- 17036923
TI  - Association of genetic variation within UBL5 with phenotypes of metabolic
      syndrome.
AB  - The BEACON gene was initially identified using the differential display
      polymerase chain reaction on hypothalamic mRNA samples collected from lean and
      obese Psammomys obesus, a polygenic animal model of obesity. Hypothalamic BEACON
      gene expression was positively correlated with percentage of body fat, and
      intracerebroventricular infusion of the Beacon protein resulted in a dose
      dependent increase in food intake and body weight. The human homolog of BEACON,
      UBL5, is located on chromosome 19p in a region previously linked to quantitative
      traits related to obesity. Our previous studies showed a statistically
      significant association between UBL5 sequence variation and several obesity- and
      diabetes-related quantitative physiological measures in Asian Indian and
      Micronesian cohorts. Here we undertake a replication study in a Mexican American
      cohort where the original linkage signal was first detected. We exhaustively
      resequenced the complete gene plus the putative promoter region for genetic
      variation in 55 individuals and identified five single nucleotide polymorphisms
      (SNPs), one of which was novel. These SNPs were genotyped in a Mexican American
      cohort of 900 individuals from 40 families. Using a quantitative trait linkage
      disequilibrium test, we found significant associations between UBL5 genetic
      variants and waist-to-hip ratio (p = 0.027), and the circulating concentrations
      of insulin (p = 0.018) and total cholesterol (p = 0.023) in fasted individuals.
      These data are consistent with our earlier published studies and further support
      a functional role for the UBL5 gene in influencing physiological traits that
      underpin the development of metabolic syndrome.

PMID- 17036924
TI  - Body mass index and chronic energy deficiency of adult males of Central Indian
      populations.
AB  - Data on body weight, height, and sitting height from 11,496 adult males, age 18
      62 years, belonging to 38 different populations of five major social groups
      (scheduled tribes, scheduled castes, "other backward castes," general castes, and
      Muslims) of Central India were taken for our analysis to assess the nutritional
      status of these groups. Cormic index and body mass index (BMI) were computed, and
      an analysis of variance (ANOVA) was carried out among different populations as
      well as among social groups separately on Cormic index and BMI. Shape, size, and
      generalized distances among the different social groups were computed and
      dendrograms were drawn. The level of malnutrition is the lowest among the general
      castes. The opposite is the case with the scheduled castes and scheduled tribes.
      Comparison of the coefficient of variation shows that there is variation in
      weight and BMI but that there is no marked variation in the other anthropometric
      variables. The ANOVA on Cormic index and BMI suggests that the people within a
      population are more homogeneous than the people between populations. There is a
      positive but statistically insignificant correlation between Cormic index and
      BMI. The five social groups differ more in size distance than in shape distance.
      According to the dendrogram of generalized distance values, the Muslims and the
      general castes can be grouped into one cluster and the scheduled castes,
      scheduled tribes, and other backward castes can be grouped into another cluster.

PMID- 17036925
TI  - Genetic variation at the mitochondrial DNA 9-bp repeat locus in the Sakha of
      Siberia.
AB  - Genetic variation at the mitochondrial DNA 9-bp repeat locus was assayed in 779
      Sakha from Siberia. Fourteen deletion (1.8%), nine triplication (1.2%), and two 4
      repeat alleles (0.26%) were identified. Several of these alleles were also
      detected as heteroplasmies. Among the four heteroplasmic individuals identified
      (0.51%), three different combinations of repeat alleles were present: 1/2, 2/3,
      and 2/3/4 copies. Hypervariable region I (HVRI) sequencing revealed that three
      different sets of haplogroups were associated with the three most frequent 9-bp
      polymorphisms: (1) haplo-groups B, T, and W for deletions; (2) haplogroups C, D,
      and K for triplications; and (3) haplogroups C, D, and T for heteroplasmies. Both
      of the two 4-repeat alleles were associated with haplogroup D. We detected more
      types of 9-bp polymorphisms and more genetic variation within classes of
      polymorphism than previously reported for any single population. We also present
      the largest and most geographically diverse sampling of the Sakha population to
      date. No neighboring populations have been reported to carry a non-haplogroup B
      deletion, triplication, or heteroplasmy, suggesting that shared ancestry or
      admixture or both are unlikely explanations for the presence of these
      polymorphisms in the Sakha. The identification of high levels of variation may be
      a function of the large sample size and the in-depth analysis of all derived
      polymorphisms. Further study of the Sakha is warranted to determine whether the
      level of variation is unexpectedly high, especially in light of the presence of
      different heteroplasmies, which suggests multiple recent events.

PMID- 17036926
TI  - Genetics of dermatoglyphic asymmetry in Vaidyas of West Bengal, India.
AB  - In this study of the genetics of dermatoglyphic asymmetry, we collected bilateral
      finger and palm prints of 824 individuals from 200 families including 2
      generations from an endogamous caste (Vaidya) in Barasat, North 24-Parganas
      District, West Bengal. Two main types of asymmetry (fluctuating asymmetry and
      directional asymmetry) were calculated between the two hands. The study includes
      familial correlation between first-degree relatives, principal-components
      analysis, and maximum-likelihood-based heritabilities (by pedigree analysis). We
      found, first, that familial correlations in all possible pairs of relationships
      (except spouse correlation) were weak but positive; some were even statistically
      significant. No indication of assortative mating was observed, but the influence
      of maternal environment could not be discarded. The results also showed that X
      chromosome linkage does not seem to be involved. A second major finding is that
      five principal factors could be extracted from all these asymmetric traits,
      explaining 74.207% of the overall cumulative variance. Asymmetry of finger and
      palmar areas were clearly separated by factor. In addition, the heritabilities of
      the extracted five factors were in the range of 8-24%. These estimates are in
      agreement with some previously published data. The heritabilities of the factors
      describing palmar asymmetry are slightly lower than those describing finger
      asymmetry. The present results support the hypothesis that both types of
      asymmetry have a genetic basis and are influenced by the intrauterine
      environment.

PMID- 17036927
TI  - Frequencies of ABO, MNSs, and Duffy phenotypes among blood donors and malaria
      patients from four Brazilian Amazon areas.
AB  - We compared the serological phenotypic frequencies of ABO, MNSs, and Duffy in 417
      blood donors and 309 malaria patients from four Brazilian Amazon areas. Our
      results suggest no correlation between ABO phenotype and malaria infection in all
      areas studied. We observed significant correlation between the S +s +, S +s -,
      and S -s + phenotypes and malaria infection in three areas. Some of the Duffy
      phenotypes showed significant correlation between donors and malaria patients in
      different areas. These data are an additional contribution to the establishment
      of differential host susceptibility to malaria.

PMID- 17036929
TI  - ABO and Rh D polymorphism among Tibetans in India.
AB  - A study of ABO and Rh D polymorphisms was conducted on 923 Tibetans living in
      exile in four different places (both high and low altitudes) in India. The
      frequencies of alleles p, q, and r for the ABO blood group system were found to
      be 0.1295, 0.2544, and 0.6152, respectively, and for alleles D and d of the Rh
      blood group system the allele frequencies were 0.9428 and 0.0572, respectively,
      for the total data. No significant difference was found for the allele
      frequencies among the four places for the two blood group systems. The allele
      frequencies were in Hardy-Weinberg equilibrium for the ABO blood group system and
      show East Asian affinity for the Tibetans.

PMID- 17036928
TI  - Genetic heterogeneity among three Adi tribes of Arunachal Pradesh, India.
AB  - We studied the distribution of ABO blood groups among three little known
      subtribes of the Adi tribe, namely, the Panggi, Komkar, and Padam, of the East
      and Upper Siang districts of Arunachal Pradesh, India. Blood group O was the
      predominant group in the Komkar and Padam, whereas group A was the predominant
      group in the Panggi. Blood group AB was found to be the least frequent group in
      all three studied populations. The populations showed significant differences in
      blood groups A (43% in Panggi, 23% in Komkar, and 18% in Padam) and O (33% in
      Panggi, 54% in Komkar, and 61% in Padam). The chi-square test indicated
      significant deviation from Hardy-Weinberg equilibrium, suggesting high
      heterogeneity among the tribes.

PMID- 17036930
TI  - CYP2A6 polymorphism reveals differences in Japan and the existence of a specific
      variant in Ovambo and Turk populations.
AB  - CYP2A6 is a polymorphic enzyme, and CYP2A6 genotype has been shown to be
      associated with smoking habits and lung cancer. We investigated CYP2A6
      polymorphism in Japanese from four different geographic areas of Japan and in the
      Ovambo and Turk populations. Using two polymerase chain reaction restriction
      fragment length polymorphisms (PCR-RFLPs), we identified the functionally
      important variants of CYP2A6: *1A, *1B, *1F, *1G, *4A, and *4D. In the Japanese
      population the highest frequencies of the CYP2A6*1A allele were observed in
      subjects from the Fukuoka (Kyushu Island) and Ehime (Shikoku Island) prefectures,
      whereas subjects in Shimane and Tottori (both located on the Japan Sea side of
      Honshu Island) showed the highest frequencies of the CYP2A6*1B allele. In the
      Tottori and Shimane groups no subject was homozygous for the CYP2A6*4A allele, a
      whole gene deletion type that is prevalent among Asians. In the Ovambo and Turk
      populations the CYP2A6*1A allele was predominant. Furthermore, two alleles
      undetected in the Japanese were observed in these latter two ethnic groups:
      CYP2A6*1G was found solely in the Ovambos, and CYP2A6*1F was found solely in the
      Turks. The present study is the first to show interprefecture differences in
      CYP2A6 polymorphism in Japanese who live in relatively close but distinct
      geographic areas; this is also the first study to evaluate CYP2A6 variations
      among these Japanese and the Ovambo and Turk populations. The distribution
      results of these alleles could help to define the true significance of CYP2A6
      polymorphism as a genetic susceptibility marker in worldwide populations.

PMID- 17036931
TI  - Short tandem repeat polymorphism in the flanking region of the human
      phosphoglycerate kinase gene in a Japanese population.
AB  - The human phosphoglycerate kinase (PGK1) gene is located within Xqll-Xql3 and is
      closely linked to the androgen receptor gene within a region implicated in a
      number of X-chromosome-linked urologic disorders. A polymorphism of a TATC short
      tandem repeat (STR) is present downstream from the PGK1 3' nuclease-sensitive
      site. We present the PGK1 flanking STR sequence and population genetic data for
      190 Japanese males and 83 Japanese females. Ten STR alleles and 29 genotypes were
      identified in the population. Five alleles--*10, *11, *12, *13, and *14--were
      common in the Japanese with frequencies greater than 10%. No significant
      deviations from Hardy-Weinberg equilibrium were established. The power of
      discrimination was 0.993 for females and 0.819 for males; heterozygosity was
      0.759 for females; and the polymorphic information content was 0.936. These data
      indicate that this STR locus shows a high degree of polymorphism in this Japanese
      population and may prove to be a useful genetic marker in forensic medicine, in
      determining the clonality of neoplasms, and potentially in studying
      predisposition to prostate cancer and other urologic diseases.

PMID- 17036932
TI  - Revolution in Massachusetts may spread to other states.

PMID- 17036933
TI  - Specialty pharmacy grows as cost-control option.

PMID- 17036934
TI  - Malpractice premiums constitute small component of expenses.

PMID- 17036935
TI  - Managed Medicare revitalized. Feel-good plan of the decade.

PMID- 17036936
TI  - Pharma tackles patient adherence.

PMID- 17036937
TI  - PBMs raise the curtain.

PMID- 17036938
TI  - We can't avoid tough decisions forever. Interview by Patrick Mullen.

PMID- 17036940
TI  - Modest investment in 'coaching' seems to lead to lowered costs.

PMID- 17036941
TI  - Remarkable work went into designing the new HPV vaccine.

PMID- 17036939
TI  - Compliance with antithrombotic guidelines.
AB  - Venous thromboembolism (VTE) remains a significant threat to public health
      despite the availability of effective and safe prophylactic measures and
      treatments. Guidelines based on randomized clinical trials are available to
      improve the management of thromboembolic disease. However, gaps exist between
      recommendations and clinical practice, and many patients are unnecessarily
      exposed to the risk of a deep vein thrombosis or potentially fatal pulmonary
      embolism. Barriers responsible for poor compliance with current antithrombotic
      guidelines include lack of familiarity with recommendations, overestimation of
      bleeding risk, underestimation of thrombotic risk, and logistical limitations of
      health care management systems. Improving compliance is a complex task, but
      successful initiatives rest upon improving thrombotic risk-assessment methods and
      facilitating appropriate prescribing of prophylaxis. Multifaceted,
      interdisciplinary strategies involving risk-assessment models, electronic
      reminders, and audit and feedback show the most potential to improve compliance
      with guidelines.

PMID- 17036942
TI  - Payers, consumers benefit as patents expire.

PMID- 17036944
TI  - [Histopathologic diagnosis in colorectal cancer screening: guidelines].

PMID- 17036943
TI  - [Protocol for diagnostic assessment of sentinel lymph node in breast pathology: a
      proposal of SIAPEC-IAP, Piemonte Region, Italy].

PMID- 17036945
TI  - Myxoid tumor of soft tissue.
AB  - Focal myxoid change is a well-recognised feature of synovial sarcoma, but the
      presence of a predominantly myxoid stroma is rare. We describe a new case of
      myxoid synovial sarcoma in which marked myxoid change initially obscured the
      diagnosis leading to confusion with malignant peripheral nerve sheath tumor. The
      patient was a 16 year old man who presented with a left dorsal foot tumor. The
      diagnosis of synovial sarcoma was suspected on histological and
      immunohistochemical studies and confirmed with cytogenetic analysis. Recognition
      of this rare histologic variant of synovial sarcoma is important because it can
      easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting
      in suboptimal therapy.

PMID- 17036946
TI  - Syringocystadenoma papilliferum: report of 8 cases.
AB  - Syringocystadenoma papilliferum (SCAP) is a rare cutaneous adnexal neoplasm with
      variable clinical appearance and characteristic histology. It arises in about one
      third of cases within a sebaceous hamartoma (SH) and in this case, multiple other
      benign adnexal neoplasms may be associated with it. We report the clinical and
      pathological data of 8 cases of syringocystadenoma papilliferum. The age at the
      time of the diagnosis varied from 3 to 48 years with an average age of 28 years.
      Three tumors were localized in the scalp, 2 in the trunk, and 3 others of unusual
      locations: 1 in the eyelid, 1 in the thigh and 1 in the popliteal fossa.
      Histopathological examination revealed 3 SCAP occurring within SH. The SCAP
      observed in the eyelid was associated with an apocrine cystadenoma without
      features of SH. The four others were not associated with any other lesion.

PMID- 17036947
TI  - Sarcomatoid renal cell carcinoma in a young adult.
AB  - Sarcomatoid renal cell carcinoma (SRCC) is an uncommon, aggressive renal cell
      carcinoma (RCC) accounting for 1.2% to 12.3% of renal cell carcinomas. SRCC may
      arise from any RCC subtype as it probably results from the de-differentiation of
      any renal epithelial malignancy. SRCC is characterised by a rapid progression and
      high metastatic rate. Currently there is no specific effective treatment for it.
      We report a new case of a 32-year-old man presented with two months backache.
      Ultrasound revealed a 7.5 cm heterogeneous mass at the inferior pole of the left
      kidney. A nephrectomy was performed. Histological study diagnosed a sarcomatoid
      renal cell carcinoma. The patient was doing well 6 months after initial surgery
      and then was lost to follow-up.

PMID- 17036948
TI  - [Ovarian oxyphilic Sertoli cell tumor: case report and review of the literature].
AB  - Ovarian oxyphilic Sertoli cell tumor is a rare neoplasm (only three cases were
      reported in literature). Sometimes the rarity itself of a lesion raises some
      problem in the diagnostics, especially if the case is send to several
      consultants. An unusual case of ovarian neoplasm came to our attention, and we
      sent some slides of the case to two well known referees of different Departments
      of Pathology. Pathologist 1 made a diagnosis of endometrioid adenocarcinoma,
      while Pathologist 2 made the diagnosis of oxyphilic Sertoli cell tumor. He sends
      the same slides to Pathologist 1, who confirmed his diagnosis. The two different
      diagnosis set different managements of the lesion for the clinician, but overall
      they set the pathologist who requested the consultation in a difficult position.
      In fact, when a pathologist sends to two experienced consultants a case, he
      really thinks to solve definitely the case itself. Unfortunately, sometimes it
      does not happen.

PMID- 17036950
TI  - [When old people fall].

PMID- 17036951
TI  - [Complaints after meat meal: spoiled meat gotten?].

PMID- 17036949
TI  - Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
      soft tissue: new entities and new variants of old entities recorded during the
      last 25 years. Part XI: Excerpta IX.

PMID- 17036952
TI  - [Stable coronary disease patients: more harm than benefit from heart catheter?].

PMID- 17036953
TI  - [Heart catheter in angina pectoris: must we set stricter indications?].

PMID- 17036954
TI  - [Old patient with atrial fibrillation: do you too hesitate to use
      anticoagulants?].

PMID- 17036955
TI  - [For prevention of cardiovascular diseases: statins in old age?].

PMID- 17036956
TI  - [Dilemma of antihypertensive therapy: high blood pressure diminishes, potency
      sometimes, too].

PMID- 17036957
TI  - [Untrained, with heart disease, diabetic: who may go to the mountains?].

PMID- 17036958
TI  - [Sunburn -- or yet not?].

PMID- 17036959
TI  - [Whether the patient has heart or lung disease or diabetes, sport is the
      cornerstone of therapy].

PMID- 17036960
TI  - [The metabolic syndrome and sports].
AB  - Lack of exercise and overweight are the causes of the metabolic syndrome (MTS),
      which are currently acquiring almost epidemic proportions. Endurance training,
      practiced alone or in combination with strength training, has a positive
      influence on the insulin resistance that is at the heart of MTS. Endurance
      training has a promoting effect in particular on the uptake of glucose by muscle
      cells. Strength training reduces insulin resistance, and increases muscle mass
      and, as a result, at the same time also the volume available for the uptake of
      glucose from the blood. In addition, strength training also reduces visceral fat.
      For the purpose of weight reduction in patients with MTS, the training-related
      calorie consumption must be appreciably more than 2,000, and preferably should be
      around 3000-3500 kcal/week.

PMID- 17036961
TI  - [Chronic obstructive pulmonary disease and sports].
AB  - From a moderate COPD onward, physical training is an essential component of
      treatment. In recent years, it has become increasingly evident that endurance
      training alone does not suffice to counter the progressive deconditioning
      process. Since the muscular strength of COPD patients is significantly reduced
      vis-a-vis healthy subjects, and this makes a considerable contribution to the
      limitation of performance, functional health can be improved in particular by
      adding strength training to endurance training. This applies all the more so
      since a decrease in muscle mass is associated with a worsening of the prognosis.
      In view of the fact that the ventilatory load is sometimes above the maximal
      breathing capacity, training should be oriented to the patient's daily
      requirements, in particular in advanced COPD. Furthermore, breathing and movement
      techniques that spare the patient's resources should be taught.

PMID- 17036962
TI  - [Physical activity in patients with renal insufficiency and patients on
      dialysis].
AB  - Regular exercise as a measure aimed at preventing renal failure results in a
      positive influence on blood pressure, a reduction in weight, reduction in
      peripheral insulin resistance, and a reduction in vessel rigidity.The same
      applies to patients who already have renal failure. With regard to weight
      reduction, however, it must be remembered that in the terminal stage of the
      disease, an elevated BMI is associated with a higher life expectancy, since with
      the need for dialysis a catabolic process with muscular atrophy and a loss of
      stored fat begins. In this situation, the aim of physical activity is to help
      reduce mortality in dialysis patients by improving cardiorespiratory function and
      muscular strength, as well as their quality of life.

PMID- 17036963
TI  - [Biologics in the treatment of psoriasis].
AB  - Currently, psoriasis is seen as a T-cell-mediated autoimmune disease that is
      characterized by an increased expression of pro-inflammatory cytokines. The
      clarification of this pathogenetic cascade uncovered a number of points of
      departure for the development of causal therapy and led to the introduction of
      new medications--the so-called biologics. The following have already been
      approved in Germany: infliximab, etanercept, efalizumab and adalimumab. These are
      described, and their advantages and disadvantages in the clinical setting are
      discussed.

PMID- 17036964
TI  - [Suspected epilepsy: clarification of convulsions].

PMID- 17036965
TI  - [Quality assurance in the medical practice: how well do we doctors really do our
      work?].

PMID- 17036966
TI  - [The electronic prescription and its consequences: physicians need waiting room
      like a railroad station].

PMID- 17036967
TI  - [Effect of angiotensin II on transforming growth factor beta-induced fibroblast
      proliferation in human skin].
AB  - OBJECTIVE: To observe the effect of angiotensin II (Ang II) or/and transforming
      growth factor beta (TGF-beta) on human skin fibroblast proliferation, and to
      explore the possible signaling mechanism involved in their actions. METHODS:
      Cultured human skin fibroblasts were treated with different concentrations of Ang
      II (1 x 10(-10), 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L) , TGF-beta(0.1, 1.0
      and 10.0 ng/ml), and 1 x 10(-10) mol/L Ang II + 0.1 ng/ml TGF-beta, respectively.
      The cell proliferation was determined by 3H-thymidine (3H-TdR) incorporation. The
      phosphorylation of extracellular signal-regulated kinases (ERK) was detected by
      Western blot. RESULTS: Ang II at 1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L or TGF
      beta at 1.0, 10.0 ng/ml increased 3H-TdR incorporation into cultured skin
      fibroblasts dose-dependently. Ang II and TGF-beta at lower doses (1 x 10(-10)
      mol/L and 0.1 ng/ml, respectively) did not affect 3H-TdR incorporation into
      fibroblasts (P>0.05), whereas co-administration of both Ang II and TGF-beta at
      these doses significantly increased 3H-TdR incorporation into fibroblasts
      (P<0.05). Ang II at 1 x 10(-7) mol/L or TGF-beta at 10.0 ng/ml significantly
      increased ERK phosphorylation of fibroblasts after stimulation (P<0.01). Smaller
      doses of Ang II (1 x 10(-10) mol/L) or TGF-beta (0.1 ng/ml) did not influence ERK
      phosphorylation of fibroblasts, whereas co-administration of Ang II and TGF-beta
      at these doses significantly enhanced ERK phosphorylation (P<0.05). Total protein
      levels of ERK did not differ at different doses. CONCLUSION: These results
      indicate that Ang II and TGF-beta synergistically increase skin fibroblast
      proliferation, which is at least partly via enhancement of ERK activity.

PMID- 17036968
TI  - [Influence of lipopolysaccharide on the biological characteristics of skin
      fibroblasts and its potential role in wound healing].
AB  - OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS) on the
      proliferation and collagen synthesis of normal human skin fibroblasts so as to
      elucidate its relation with skin wound healing. METHODS: Fibroblasts were
      isolated and cultured in vitro, and then exposed to different doses of LPS(0.005,
      0.010, 0.050, 0.100, 0.500, and 1.000 microg/ml) from E. coli055:B5 respectively.
      Then the absorbance (A) value of fibroblasts was determined with the
      colorirneteric thiazolyl blue (MTT) assay, and the cell number was counted under
      inverted phase contrast microscope from the 1st day to the 9th day after LPS
      administration, and collagen synthesis of fibroblasts in culture medium was
      measured with the method of pepsin digestion after incorporation of 3H-proline
      into stable, single-layered, confluent fibroblasts at 7 days after LPS
      administration. RESULTS: Compared with control group, A value increased with the
      increasing concentration of LPS (0.005 microg/ml-0.500 microg/ml) and LPS of
      0.100 microg/ml group had the strongest effect. The difference was remarkable
      from the 5th day to the 9th day(P<0.05). A value decreased when challenged with
      the LPS of 1.000 microg/ml and the difference was remarkable from the 3rd day to
      the 9th day(P<0.05). Cell number increased with the administration of LPS of
      different concentrations (0.005 microg/ml-0.500 microg/ml) and LPS of 0.100
      microg/ml group had the strongest effect. The difference was remarkable from the
      1st day to the 6th day(P<0.05). Cell number decreased remarkably when challenged
      with LPS of 1.000 microg/ml and the difference was remarkable from the 2nd day to
      the 9th day (P < 0.05). Collagen synthesis increased when challenged with LPS of
      different concentrations (0.005 microg/ml-0.500 microg/ml) and the 0.100
      microg/ml group had the strongest effect. However, when the dose of LPS reached
      1.000 microg/ml, it inhibited collagen synthesis. CONCLUSION: LPS could promote
      the proliferation and collagen synthesis of fibroblasts within a certain range of
      low doses, but over-high dose of LPS might inhibit the proliferation and collagen
      synthesis of fibroblasts, suggesting that LPS of certain concentrations might
      contribute to wound healing, while excessive LPS has negative effect on wound
      healing.

PMID- 17036969
TI  - [Preliminary dissection of the blood supply on myocutaneous flap of rectus
      abdominis on hypogastric zone].
AB  - OBJECTIVE: To investigate the location of the artery correlated with rectus
      abdominis musculocutaneous flap in order to promote the reconstruction of the
      breast after radical mastectomy for breast cancer. METHODS: An anatomic study was
      carried out on 15 cadavers of 30 sides, which were immersed in paraformaldehyde
      less than six months. Whole thorax-epigastric wall was cutterd, which scale was
      from subclavian as upper limit to inguinal ligament, the lower limit across left
      and right of middle axillary. Veins or arteries of inferior epigastric and
      internal thorax in hang were injected with red or blue ink to show all of vessel
      branches. RESULTS: The external diameters of both the superior epigastric
      arteries and inferior vessels were 1.87 +/- 0.28 mm and 2.25 +/- 0.32 mm
      respectively. The myocutaneous arteries from inferior abdomen vessels had an
      intensive horizontal distribution on hilum. The perforators significantly
      decreased but could be found to pass through anterior rectus sheath in Rand. The
      distances between lateral perforators and I , II and III parts in external edge
      of anterior rectus sheath were 1.22, 1.46 and 1.57 cm, respectively; and the
      distances between medial perforators and I, II, and III parts at median line were
      1.54, 1.62, 1.66 cm. Perforators were more thick and intensive near hilum than in
      other part. The subcostal arteries derived from inferior abdomen artery and 1.25
      +/- 0.37 cm away from costal arch. After dividing into subcostal artery, the
      outer diameter of 67 percent of subcostal artery was bigger than that of inferior
      abdomen arteries. The branches of subcostal arteries were distributed at the 2/3
      lateral rectus abdominis, forming an extensive choke anastomosis system with
      intercostal anterior artery and vessels supplied diaphragmatic muscle. The rectus
      abdominis at the level of xyphoid was supplied by a branch came from inferior
      thorax artery, which diverged epigastric vessels at the same time. CONCLUSION:
      During the process of making the inferior transverse rectus abdominis
      musculocutaneous flap base on superior epigastric vessels and superior rectus
      abdominis, reservation of pro-theca edge 1 cm of rectus abdominis can protect
      inferior abdomen artery from injury. Reservation of more than 2 cm pro-theca and
      rectus abdominis below costal arch at the flag will protect effectively subcostal
      artery from injury. No damage of subcostal arteries can influence the survival of
      musculocutaneous flap.

PMID- 17036970
TI  - [Anatomic basis and clinical application of modified peroneal arterial cutaneous
      branch nutritional flap].
AB  - OBJECTIVE: To observe the anatomic basis and the clinical application of the
      modified peroneal arterial cutaneous branch nutritional flap. METHODS: Twenty
      sides of lower limb of adult colyseptic cadavers and 5 sides of lower limb of
      adult fresh cadavers were used to detect the cutaneous branches of the peroneal
      artery. The position where the cutaneous branches come from the peroneal artery
      and the diameter of the cutaneous branches were recorded. From September 2003 to
      June 2005, 10 cases of skin and soft tissue defects in the region of
      metatarsophalangeal point with the modified peroneal arterial cutaneous branch
      nutritional flap, in which the cutaneous branches from the peroneal artery 11.0
      +/- 1.7 cm upon the lateral malleolus were added. The defect size was 10 cm x 6
      cm to 15 cm x 10 cm. The flap size was 11.0 cm x 6.5 cm to 16.0 cm x 11.0 cm.
      RESULTS: There is a stable cutaneous branches from peroneal artery 11.0 +/- 1.7
      cm upon the lateral malleolus. The diameter of this cutaneous branches at the
      origin is 1.45 +/- 0.12 mm. The distance between the cutaneous branches entrance
      of the deep fascia and the line of the sural nerve nutritional artery flap was
      15.70 +/- 1.20 mm. All 10 flaps survived. The blood supply and venous return of
      the skin flaps were good. The 10 patients were followed up from 6 to 12 months.
      The shape of the flaps was satisfactory. The texture and the color and luster of
      the flaps were similar to the adjacent skin. The functions of the feet were good.
      The two-point discrimination was 11-18 mm. CONCLUSION: The modified peroneal
      arterial cutaneous branch nutritional flap has good blood supply. It can reverse
      to a long distance and can repair large skin defects.

PMID- 17036971
TI  - [Microsurgical anatomy of the facial nerve trunk in facial-hypoglossal nerve
      anastomosis].
AB  - OBJECTIVE: To study the microsurgical anatomy of the facial nerve (FN) trunk and
      provide some important morphometric data about facial-hypoglossal nerve
      anastomosis (FHA). METHODS: Bilateral microsurgical dissection was performed on
      the heads of 9 cadavers fixed with formalin with three different methods. In the
      first method, the posterior belly of the digastric muscle was used as a mark, and
      the FN trunk was identified on the medial side of this muscle. In the second
      method, dissection was initiated at the parotid gland, the FN trunk was
      identified at its entrance into the parotid gland. In the third method, the
      styloid process was identified and traced back to the stylomastoid foramen (SMF).
      The FN trunk was identified on its emergence from the SMF. In every dissection,
      the whole FN trunk was exposed; its diameter and depth at the the SMF and its
      length were measured; its relationship, with other structures was studied.
      RESULTS: The FN invariably emerged from the cranial base through the SMF. Its
      diameter upon its emergence from the foramen was 2.57 +/- 0.60 mm. The mean
      minimal distance of the FN trunk from the skin surface in this area was 22.62 +/-
      2.88 mm. The length of the FN trunk was 15.71 +/- 1.97 mm. The distance between
      the bifurcation and the mastoidale was 18.20 +/- 4.41 mm. The distance between
      the bifurcation and the mandibular angle was 39.91 +/- 8.38 mm. The distance
      between the mastoidale and the SMF was 17.91 +/- 2.68 mm. The branches from the
      FN trunk proximal to its bifurcation were the posterior auricular nerve, the
      digastric muscle nerve and the stylohyoid muscle nerve. CONCLUSION: The third
      method to expose the FN trunk on its emergence from the SMF is safe and reliable.
      It is feasible to use only part of the hypoglossal nerve fibers for anastomosis
      with the FN trunk.

PMID- 17036972
TI  - [Expanded clavipectoral skin flap combined with reverse axis skin flap in
      repairing cervical scar contracture deformity after burn].
AB  - OBJECTIVE: To evaluate the effect of a combined cervical expanded skin flap in
      repairing cervical scar contracture deformity after burn injury. METHODS: From
      April 2001 to May 2003, 16 cases (10 males and 6 females) of scar contracture
      deformity in the cervix were treated with expanded clavipectoral axis skin flap
      combined with reverse axis skin flap. The tissue expanders were embedded under
      the part containing cutaneous branches of transverse cervical artery in cervical
      segments and the second and/or the third perforating branch of internal thoracic
      artery for the first operation. Normal saline was injected regularly. The
      expanded clavipectoral skin flap and reverse axis skin flap with perforating
      branch of internal thoracic artery were designed, the scar in the cervix was
      loosed or dissected according to the size of the skin flaps, the skin flaps were
      transferred to cover the wound, and the contracture deformity in the cervix was
      corrected. The size of the flaps were 9 cm x 5 cm-15 cm x 7 cm. RESULTS: All skin
      flap survived. The function and appearance of the cervix was improved
      significantly after 6-30 months follow-up. However, venous return dysfunction in
      reverse perforating branch of internal thoracic artery occurred in 1 case, and
      blood circulation was improved after treatment. CONCLUSION: Expanded
      clavipectoral axis skin flap combined with reverse axis skin flap can be used to
      repair scar contracture deformity in cervix, which lessen scar and abate the
      chance to contract again.

PMID- 17036973
TI  - [Combined scapular/parascapular bilobar flaps for reconstruction of severe neck
      contracture].
AB  - OBJECTIVE: To discuss the reconstruction of severe neck contracture by
      transplanting combined scapular/parascapular bilobar flaps, and the probability
      to reestablish three-dimensional movement of the neck. METHODS: From January 2003
      to November 2004, 9 cases of sustained severe neck contractures were treated
      (aged 9-32 years). The combined scapular/parascapular bilobar flaps, pedicled on
      the circumflex scapular vascular bundle, were microsurgically used to cover the
      soft tissue defect after excision of hypertrophic scar and release of
      contracture. The maximum size of the combined bilobar flap was 20 cm x 8 cm to 20
      cm x 11 cm, while the minimum one was 15 cm x 4 cm to 15 cm x 6 cm. RESULTS: The
      combined scapular/parascapular flaps were successfully used to treat 9 cases of
      severe neck contracture. All patients were satisfied with the final functional
      and aesthetic results. There was no recurrence during 3-9 months follow-up for 8
      patients. The cervicomental angle was 90-105 degrees. CONCLUSION: The combined
      bilobar scapular/parascapular flap, providing a large area of tissue for coverage
      in three dimensions with a reliable blood supply by only one pedicle anastomosis
      during operation, is a good option for reconstruction of the severe neck
      contracture.

PMID- 17036974
TI  - [Reconstruction of oral muco-defects with buccal fat pad flap].
AB  - OBJECTIVE: To evaluate the clinical outcome of the buccal fat pad flap in
      reconstruction of defects of the oral mucosa. METHODS: From May 1998 to July
      2004, 42 patients with oral muco-defects were treated with buccal fat pad flap.
      Of them, there were 26 males and 16 females, aging 25-76 years. The defect was
      caused by buccal squamous carcinoma in 7 cases, by buccal leukoplakia in 5 cases,
      by squamous carcinoma of soft palate in 7 cases, by adenoid cystic carcinoma of
      palate in 8 cases, by carcinoma of maxillary sinus in 6 cases, by maxillo
      alveolar angioma in 5 cases and by keratocyst of maxilla in 4 cases. The
      locations were buccal mucosa, maxillary sinus and soft palate. The size of defect
      ranged from 3.0 cm x 3.0 cm to 6.5 cm x 4.0 cm. RESULTS: Forty-one cases achieved
      healing by first intention, except one case because of large defect. Edema faded
      and epithelization occurred after 4 weeks of operation. Complete epithelization
      was observed after 6 weeks of operation. Thirty-five cases were followed up 3
      months to 5 years. There were no obvious differences in layers, color,
      elasticity, and texture between repaired region and adjacent mucosa. CONCLUSION:
      The buccal fat pad flap is useful in reconstructing the muco-defects (less than
      6.5 cm in diameter) of the posterior maxilla and buccal region without
      considerable complication. The multiplex blood supply, facility in accessing and
      minimal donor site morbidity make it a reliable soft tissue graft. The main
      shortcoming is its limited size.

PMID- 17036975
TI  - [Modified transcranial approach to resect tumor around the anterior skull base
      and double tissue flap to reconstruct the anterior skull base].
AB  - OBJECTIVE: To explore better approach of resecting tumor around the anterior
      skull base and reconstructing the anterior skull base. METHODS: In November 2004,
      a 49-years-old male patient with intracranial recrudescent adenoid cystic
      carcinoma in the anterior cranial fossa was treated using modified transcranial
      approach. Neurosurgeon and rhinolaryngologist cooperated to excise the tumour
      completely, and to reconstruct anterior skull base using the pedicle periosteum
      temporal musculofascial flap (15 cm x 10 cm) and the pedicle flap of aponeurosis
      of occipitofron tails muscle and muscular fasciae (10 cm x 6 cm). RESULTS: After
      operation, the wound healed by first intention. Complication, such as infection
      and cerebrospinal rhinorrhea, did not occur. The patient was discharged 10 days
      after operation, and was followed up for 8 months, no local recurrence were
      investigated and no scar formed over the face. CONCLUSION: The modified
      transcranial approach is a relatively novel exposure that enables the skilled
      cranial base surgeon to safely resect many malignant lesions previously and to
      reconstruct the defect of anterior skull base together.

PMID- 17036976
TI  - [Study on repair approach of bilateral cleft lips and nose deformity].
AB  - OBJECTIVE: To detect the operative technique and aesthetic problem of
      reconstruction to deformity of bilateral cleft lip. METHODS: From March 2003 to
      December 2004, 26 patients with bilateral cleft lip were treated, aged 10 months
      to 11 years. Of 26 patients, there were 13 bilateral complete cleft lip and
      palate, 9 bilateral incomplete cleft lip and 4 mixed cleft lip with unilateral
      complete cleft palate. The chief design principle was keeping the length of
      prolabium. During operation, sufficient dissociation was made in the base of the
      ala base and orbicularis oris muscle to reconstruct these structures. The circle
      suture was made for the bilateral orbicularis oris muscle. The shape of vermilion
      was achieved by lateral red lip muscle flap and simultaneous simple rhinoplasty
      was performed. RESULTS: Primary healing of the incisions was achieved in all
      cases. After the 10 days-3 months follow-up, the results were satisfactory in the
      width and chubbiness of the nose bottom, the shapes of nostril and Cuspid's bow
      were good without whistle deformity. The appearance of upper lip was good in
      either dynamic or static state. CONCLUSION: Excellent shapes and function of the
      nose and lip, and opportunity for two-stage repair could be obtained with this
      method, which being believed important methods for the primary repair of
      bilateral cleft lip.

PMID- 17036977
TI  - [Clinical investigation of the combined therapy on deformed fingers after burn
      injury].
AB  - OBJECTIVE: To investigate the benefit of the combined therapy for deformed
      fingers after burn injury by comparing with the conventional one, and to sum up
      some experience. METHODS: From June 1999 to June 2004, 56 patients with deformed
      fingers entered the trial. In 28 patients of treatment group who received
      combined therapy (operation with post operational systematic convalescent care,
      group A), there were 20 males and 8 females (14-47 years), 129 fingers of 47
      hands were involved. In 28 of conventional group who received conventional
      therapy (the same operational principle, and self-convalescent-care with out
      patient service guidance, group B), there were 17 males and 11 females (18-51
      years), 107 fingers of 42 hands were involved. Before and after the therapy, the
      finger's motor function were assessed according to the Swanson method. The hand's
      motor function was assessed through the Nine Hole Peg Test. RESULTS: The follow
      up was 12-19 months in group A and 13-20 months in group B. The index of
      ankylosis (IA) of group A before therapy was 82% +/- 20%, and 45% +/- 13% after
      therapy; while the IA of group B before therapy was 78% +/- 17%, and 52% +/- 14%
      after therapy. The decreased of IA between before therapy and after therapy was
      37% +/- 15% in group A, and 26% +/- 15% in group B, showing significant
      difference between the two groups (P<0.05). The Nine Hole Peg Test value of group
      A was 28.34 +/- 5.62 s before therapy, and 20.73 +/- 4.25 s after therapy; while
      that of group B was 27.47 +/- 5.78 s before therapy, and 21.86 +/- 4.12 s after
      therapy. The decrease of the Nine Hole Peg Test value between before therapy and
      after therapy was 7.61 +/- 2.27 s in group A, and 5.61 +/- 2.94 s in group B,
      showing statistically significant difference (P<0.05). CONCLUSION: The combined
      therapy is more effective than the conventional one.

PMID- 17036978
TI  - [Thumb reconstruction with skin and soft tissue expansion].
AB  - OBJECTIVE: To evaluate a new reconstruction method for grades V and VI defect
      with flap by skin soft tissue expansion technique. METHODS: From May 1998 to
      September 2003, 8 cases of serious thumb defect were treated, including 6 males
      and 2 females, aging 18-27 years. The defect was caused by crush injury of
      machine in 6 cases and hot crush injury in 2 cases (5 cases of grade V and 3
      cases of grade VI). The expander was placed under the tenor skin and soft-tissue.
      And then normal saline was infused to expand the skin and soft tissue gradually
      till it was available for thumb reconstruction. Iliac autograft was fixed to
      residual thumb stump and covered with flap produce by expanded skin and soft
      tissue. Postoperative rehabilitation was carried out. RESULTS: All reconstructed
      thumbs were alive. After 3-24 months follow-up, all reconstructed thumbs were
      with good sensation, appearance and durable. Two-point discrimination was less
      than 5 mm. The functions of opposition, extend, abduction and endoduction were
      better in grade V thumb defect than in grade VI thumb defect. Bone union was
      achieved within 3 to 4 months. CONCLUSION: It is a convenient-to-operate and
      reliable method for thumb reconstruction. It is an alternative new reconstruction
      method for grades V and VI, thumb defect.

PMID- 17036979
TI  - [Combined treatment of refractory decubitus ulcers].
AB  - OBJECTIVE: To summarize the clinical experience in the treatment of refractory
      decubitus ulcers. METHODS: From May 1998 to March 2005, 22 patients with
      decubitus ulcers (29 decubitus ulcers) were admitted, whose age was 36-92 years.
      The lesion size was 4 cm x 2 cm to 18 cm x 15 cm. The locations of decubitus
      ulcers were the sacrococcygeal region (18 cases), the tuber ischiadicus region (6
      cases) and the trochanter major region (5 cases). Enteral nutrient was given
      orally and the wound was treated with Wuhuangyihao 8-15 days. Three diabetic
      patients were injected with insulin. According to patient's age, ulcer position,
      ulcer extent and ulcer degree, the flap type was determined. Three wounds were
      repaired by local flaps, the flap size was 6 cm x 4 cm-12 cm x 10 cm; 10 by
      fasciocutaneous flaps, 10 cm x 7 cm-20 cm x 17 cm; 9 by gluteus maximus
      myocutaneous flaps, 13 cm x 11 cm-17 cm x 14 cm; and 6 by long-head of biceps
      femoris flaps, 11 cm x 6 cm-14 cm x 7 cm. One was sutured directly. After
      operation, the patients were placed on airflow suspended bed 7-14 days. RESULTS:
      General nutritional status was improved, hemoglobin was greater than 100 g/L,
      albumen was greater than 30 g/L. Necrosis tissue was removed, granulation tissue
      turned into fresh, secretion reduced and no redness and swelling occurred in
      wound. All flaps survived and the wounds healed by first intention. After a
      follow-up of 6 months to 5 years, no patient had a recurrence, the color and
      texture of the flaps were good, the appearance was satisfactory. CONCLUSION:
      Applying the technique of combined treatment can accelerate the healing of
      refractory decubitus ulcers and improves the success of operation.

PMID- 17036980
TI  - [Experimental study on magnesium phosphate cement in fracture treatment].
AB  - OBJECTIVE: To investigate the effect of magnesium phosphate cement (MPC) to fix
      fractures. METHODS: In vitro: fifty-four pairs of fresh pig femoral heads were
      made 1 cm2 fracture and divided into 6 groups (n=9 pairs ). MPC was used to
      agglutinate fracture of femoral heads at 100% humidity and at 25 degrees C, 37
      degrees C respectively. At 30 minutes, 2 and 24 hours after agglutination, the
      biomechanical strength was measured. In vivo: the tibia plateau fracture models
      on both sides of 24 rabbits were made, one side was fixed with "L" shaped plate,
      and the other side was fixed with MPC. Then the effect of treatment was
      investigated by macrography, micrography, radiography and the In vitro: the
      adhesive ability of changes of serum electrolyte levels at 3 days, 3, 6 and 9
      weeks after operation. RESULTS: MPC was strong. At 24 hours after MPC
      agglutination, the average tensile strength was 117.16 +/- 23.29 N/cm2. In vivo:
      after 6 weeks of fixation, the X-ray results showed that all rabbits' tibia
      plateau fractures were healed without displacement, and MPC was absorbed
      gradually. The changes of serum electrolyte levels were very minimal. The
      macrography observation showed that reduction of fracture were good at 3 days
      after operation, partial MPC remained in fracture end at 3 weeks, fracture line
      disappeared at 6 weeks and good remodeling was achieved at 9 weeks after
      operation in the experimental group. The micrography observation showed that the
      interface between bone and MPC was distinct at 3 days, MPC was degraded gradually
      and trabeculae began to grow into MPC at 3 weeks, and almost all MPC was degraded
      at 6 and 9 weeks of operation. CONCLUSION: MPC is a promising biomaterial, and
      might potentially be used for fracture treatment.

PMID- 17036981
TI  - [Experimental studies on the porous calcium phosphate cement combined with
      recombinant human bone morphogenetic protein 2 for bone defects repair].
AB  - OBJECTIVE: To study in vitro sustained release behaviour of the recombinant human
      bone morphogenetic protein 2 (rhBMP-2) from the sample which porous calcium
      phosphate cement (PCPC) was combined with rhBMP-2, and to evaluate the effect of
      PCPC/rhBMP-2 composite on repairing bone defect in the animal study. METHODS:
      rhBMP-2 was absorbed into PCPC by vacuum-adsorption and freeze-dried at -40
      degrees C, the PCPC/rhBMP-2 enwrapped with chitosan as the experimental group,
      the pure PCPC/rhBMP-2 as the control group, then the sustained release of rhBMP-2
      from PCPC was determined in simulated body fluid (SBF) by UV-VIS
      spectrophotometer. At same time, the PCPC/rhBMP-2 composites with chitosan were
      implanted into the (4.2 mm x 5.0 mm femora defects of rabbits, which were
      considered as the experimental group, whereas in the control group only PCPC was
      implanted. The effect of repairing bone defect was evaluated in the 4th and 8th
      week postoperatively by radiograph and histomorphology. RESULTS: The PCPC have a
      high absorption efficiency to rhBMP-2, and the release of rhBMP-2 was sustained
      release system. The release of rhBMP-2 from PCPC in the experimental group (99%
      after 350 hours) was slower than that in the control group (100% after 150
      hours). In the experimental group, the radiological and histomorphological
      evaluations showed that the interfaces between the materials and host bones
      became blurred both at 4th and 8th week. The implanted materials were partially
      absorbed, and the implanted areas exhibited the formation of new bone. In the
      control group, a little amount of new bones was observed. CONCLUSION: The PCPC
      shows great clinical potential as a carrier for rhBMP-2. The PCPC/rhBMP-2
      composite possesses much potentialities of osteoinductivity and the ability of
      repairing bone defect, so it can be used as a novel bone substitute clinically.

PMID- 17036982
TI  - [Preparation of gentamicin-impregnated bone allograft and experimental study on
      treatment of infective bone defect].
AB  - OBJECTIVE: To study and prepare a new kind of bone graft, which has osteogenesis,
      local anti-infective function and low immunogenicity. METHODS: Gentamicin
      impregnated bone was prepared by means of ultrasonic and vacuum, the release of
      gentamicin in vivo was measured by inhibition bacteria. Ten healthy male adult
      sheep were made animal infection models of thigh bone or humerus defect of 6 mm x
      6 mm x 20 mm at size, and the defect was inoculated into 1 ml 5 x 10(10) CFU/ml
      Staphylococcus aureus. The animals were randomly divided into the experimental
      group (n=5, the bone graft with gentamicin was implanted) and the control group
      (n=5, the bone graft without gentamicin). Macroscopic, WBC count, radiological,
      and histological investigations were carried out to evaluate the anti-infective
      and osteosis capability. RESULTS: The concentrations of gentamicin were 46.1
      microg/ml in bone allograft and 17.3 microg/ml in muscles after 1 day. The
      concentrations of gentamicin exceeding the minimum inhibitory concentration
      lasted for 14 days in vivo. WBC in the control group was higher than that in the
      experimental group. In the control group, 1 case died owing to septicemia 3 weeks
      after operation. The implanted bones were wrapped in pus 4 and 6 weeks, and the
      defects were filled with fibre tissue 8 and 10 weeks after operation. In the
      experimental group, 1 case was infected, the others had a good concrescence. The
      bone allografts began to integrate with adjacent bone after 4-8 weeks and
      integrate well after 12 weeks. The X-ray and histological observation showed that
      new bone formed and took the place of bone allograft. CONCLUSION: The gentamicin
      impregnated bone allograft was of a good sustained release feature in vivo, local
      anti-infection and osteogenesis. It might be an ideal bone grafting material for
      bone defects with infection.

PMID- 17036983
TI  - [Assessment of therapeutic results for simple bone cyst with percutaneous
      injection of autogenous bone marrow].
AB  - OBJECTIVE: To evaluate the therapeutic results of percutaneous injection of
      autogenous bone marrow for simple bone cyst and to analyze the prognostic factors
      of the treatment. METHODS: From March 2000 to June 2005, 31 patients with simple
      bone cysts were treated by percutaneous injection of autogenous bone marrow. Of
      31 patients, there were 18 males and 13 females, aged 5 years and 7 months to 15
      years. The locations were proximal humerus in 18 cases, proximal femur in 7 cases
      and other sites in 6 cases. Two cases were treated with repeated injections. The
      operative process included percutaneous aspiration of fluid in the bone cysts and
      injection of autogenous bone marrow aspirated from posterior superior iliac
      spine. The mean volume of marrow injected was 40 ml (30-70 ml). RESULTS: No
      complications were noted during treatment. Thirty patients were followed for an
      average of 2.2 years (1-5 years) with 2 cases out of follow-up. After one
      injection of bone marrow, 9 cysts (29.0%) were healed up completely, 7 cysts
      (22.6%) basically healed up, 13 cysts (41.9%) healed up partially and 2 (6.5%)
      had no response. The satisfactory and effective rates were 67.7% and 93.5%
      respectively. There was significant difference between active stage group and
      resting stage group(P<0.05). There were no statistically significant difference
      in therapeutic results between groups of different ages, lesion sites or bone
      marrow hyperplasia(P>0.05). CONCLUSION: Percutaneous injection of autogenous bone
      marrow is a safe and effective method to treat simple bone cyst, but repeated
      injections is necessary for some patients. The therapeutic results are better in
      cysts at resting stage than those at active stage.

PMID- 17036984
TI  - [Microsurgical treatment of arterial occlusion in lower extremity].
AB  - OBJECTIVE: To investigate the procedure and clinical effect of revascularization
      for arterial occlusion in lower extremity. METHODS: From July 1998 to March 2005,
      29 cases of arterial occlusion were treated by microsurgery. Of 29 cases, there
      22 males and 7 females, aging 22-86 years, including 9 cases of thromboangiitis
      obliterans (TAO), 17 cases of arterial sclerosis obstruction (ASO) and 3 cases of
      diabetic foot (DF). The location was the left in 17 cases, the right in 11 cases
      and both sides in 1 case. All cases were inspected by color-Doppler ultrasonic
      scanning before operation. The cases of ASO and DF were checked with MRA. The
      results of examinations showed that the locations of arteriostenosis and
      obstruction were: in 9 cases of TAO, the distal superficial femoral artery in 3
      cases, popliteal artery in 5 cases, bilateral dorsal metatarsal artery in 1 case;
      in 17 cases of ASO, common iliac artery in 2 cases, external iliac artery in 4
      cases, femoral artery in 10 cases and popliteal artery in 1 case; and were all
      superficial femoral artery in 3 cases of DF. DSA examination confirmed that there
      was appropriate outflow in 15 cases. Basing on the location and extent of the
      arterial occlusion, 11 cases were treated by the primary deep vein arterializing,
      16 cases by arterial bypass distribution and 2 cases of extensive common iliac
      arterial occlusion were amputated in the level of 1/3 distal thigh. RESULTS: The
      postoperative duration of follow-up for all cases was 3 months to 7 years. In 9
      cases of TAO, 2 healed by first intention after deterioration, 4 healed after
      changing dressing and 3 had fresh soft tissue growth after debrided superficial
      secondary necrosis. In 17 cases of ASO, 13 healed by first intention, 2 healed
      after changing dressing and 2 were amputated. In 3 cases of DF, 2 healed after
      changed dressing and debrided, 1 was aggravated with the second toe necrosis.
      CONCLUSION: Performing primary deep vein-arterialization and arterial bypass
      distribution is effective for treatment of arterial occlusion of lower extremity.
      The arterial reconstructive patency rate can be improved by microsurgical
      treatment.

PMID- 17036985
TI  - [Vascularization in transplantation of gene modified tissue engineered bone for
      repairing bone defect].
AB  - OBJECTIVE: To study the vascularization of the composite of bone morphogenetic
      protein 2 (BMP-2) gene transfected marrow mesenchymal stem cells (MSCs) and
      biodegradable scaffolds in repairing bone defect. METHODS: Adenovirus vector
      carrying BMP-2 (Ad-BMP-2) gene transfected MSCs and gene modified tissue
      engineered bone was constructed. The 1.5 cm radial defect models were made on 60
      rabbits, which were evenly divided into 4 groups randomly (n= 15, 30 sides).
      Different materials were used in 4 groups: Ad-BMP-2 transfected MSCs plus PLA/PCL
      (group A), Ad-Lacz transfected MSCs plus PLA/PCL (group B), MSCs plus PLA/PCL
      (group C) and only PLA/PCL scaffolds (group D). The X-ray, capillary vessel ink
      infusion, histology, TEM, VEGF expression and microvascular density counting
      (MVD) were made 4, 8, and 12 weeks after operation. RESULTS: In group A after 4
      weeks, foliated formed bones image was observed in the transplanted bones, new
      vessels grew into the bones, the pores of scaffolds were filled with cartilage
      callus, osteoblasts with active function grew around the microvessels, and VEGF
      expression and the number of microvessels were significantly superior to those of
      other groups, showing statistically significant difference (P<0.01); after 8
      weeks, increasingly more new bones grew in the transplanted bones, microvessels
      distended and connected with each other, cartilage callus changed into trabecular
      bones; after 12 weeks, lamellar bone became successive, marrow cavity
      recanalized, microvessels showed orderly longitudinal arrangement. In groups B
      and C, the capability of bone formation was weak, the regeneration of blood
      vessels was slow, after 12 weeks, defects were mostly repaired, microvessels grew
      among the new trabecular bones. In group D, few new vessels were observed at each
      time, after 12 weeks, broken ends became hardened, the defected area was filled
      with fibrous tissue. CONCLUSION: BMP-2 gene therapy, by up-regulating VEGF
      expression, indirectly induces vascularization of grafts, promotes the living of
      seed cells, and thus accelerates new bone formation.

PMID- 17036986
TI  - [Proliferative effect of basic fibroblast growth factor and epidermal growth
      factor on muscle derived stem cells].
AB  - OBJECTIVE: To explore the effect of basic fibroblast growth factor (bFGF) and
      epidermal growth factor (EGF) on the growth of muscle derived stem cells (MDSCs).
      METHODS: MDSCs were isolated from hindlimb muscle of 15 new born Kunming mice
      through serial preplates. 2% fetal bovine serum-containing DMEM was used to
      induce MDSCs to differentiate into skeletal muscle lineage. The expressions of
      stem cell marker Sca-1 and skeletal muscle cell marker alpha-Sarcomeric actin
      were examined by immunocytochemistry. The effect of bFGF and EGF on the
      proliferation of MDSCs was determined by MTT colorimetric microassay. The solo
      effect of bFGF or EGF at different concentrations (6.25, 12.50, 25.00, 50.00, and
      100.00 ng/ml) was examined at 96 h and the combined effect (100.00 ng/ml) was
      examined at 24, 48, 72 and 96 h. RESULTS: MDSCs were successfully isolated from
      the hindlimb of neonatal mice. Over 90% of MDSCs showed Sca-1 positive
      immunoreactivity. MDSCs could give rise to alpha-Sarcomeric actin positive
      myotubes in differentiation cultures. The proliferative effect of bFGF and EGF on
      MDSCs increased with the elevated concentration. bFGF began to show significant
      proliferative effect at 12.50 ng/ml (P<0.05). The effect increased significantly
      when the concentration reached 25.00 ng/ml from 12.50 ng/ml (P < 0.01) and
      reached a saturation point. The effect at 50.00 ng/ml or 100.00 ng/ml showed no
      significant increase when compared with that at 25.00 ng/ml. EGF had a similar
      effect to bFGF except that the saturation concentration was 50.00 ng/ml. EGF
      showed significant effect at 72 h and bFGF at 96 h (P<0.01). When they were
      applied together, significant effect was shown at 24 h (P<0.01) and much higher
      effect was observed at 48, 72 and 96 h (P<0.05). CONCLUSION: Both bFGF and EGF
      can promote the proliferation of MDSCs. The combined application reacts faster
      and stronger.

PMID- 17036987
TI  - [Experimental study on transforming growth factor beta3 gene transfecting into
      marrow mesenchymal stem cells in rabbits].
AB  - OBJECTIVE: To construct recombinant adenovirus vector containing human
      transforming growth factor beta 3 (TGF-beta3), which was transfected into marrow
      mesenchymal stem cells (MSCs) and to observe its expression. METHODS: The cDNA
      TGF-beta3 was integrated into the shuttle vector of pAdTrack-CMV and recombinated
      with adenovirus skeleton vector pAdEasy-1 by homologous recombination. Then the
      product was transfected into package cell HEK293 by lipofectamine and the
      recombinant adenovirus expressing the TGF-beta3 gene was generated. The rabbit's
      MSCs were isolated, cultivated, purified, and then transfected with recombinant
      adenovirus containing the TGF-beta3 gene. The green fluorescence protein
      expression was observed after 10 days, and the TGF-beta3 expression was observed
      in MSCs transfected by recombinated adenovirus with TGF-beta3 gene after 4 days.
      RESULTS: PCR showed that TGF-beta3 cDNA was inserted into the recombinant
      adenoviral plasmid. The recombinant virus vectors with TGF-beta3 gene were
      collected by the packaging HEK293 cells. The fusion rate of MSCs was 70%-80% with
      an intensive adhesion and uniform shape after the cultured 10th day. Fluorescent
      microscopy and immunocytochemistry demonstrated that TGF-beta3 was expressed in
      MSCs. CONCLUSION: Successful construction of human TGF-beta3 recombinant
      adenovirus and its expression in MSCs provide a basis of research for the gene
      therapy of wound healing.

PMID- 17036988
TI  - [Application of platelet-rich plasma in non-vascularized bone graft of
      maxillofacial surgery].
AB  - OBJECTIVE: To introduce the application of platelet-rich plasma (PRP) in non
      vascularised bone grafts (NVBG) of maxillofacial surgery and its potential
      mechanism in recent years. METHODS: The latest articles were extensively
      retrieved, and the potential mechanism for PRP promotes the osteogenesis was
      discussed. RESULTS: PRP promotes osteogenesis when applied to NVBG, and the
      cytokine included in platelet is thought to be the ingredient for PRP's effect.
      Some scholar has already applied PRP in the restoration of maxillofacial bone
      defect and got good results. CONCLUSION: PRP has the potential to promotes
      osteogenesis, and more studies are needed for further understanding of its
      mechanism.

PMID- 17036989
TI  - [Central projections of the rat superior laryngeal nerve].
AB  - Laryngeal nerves contain the fibres that control the laryngeal function. On the
      rat, the studies on the functional components and the real origin of the fibres
      conveyed by the superior laryngeal nerve (SLN) are few. No one of such works were
      developed using biotinylated dextrane amines (BDA), a powerful tool for tracing
      neural pathways. The aim of our study was to identify by using BDA, in the rat,
      the nuclei of real origin of the fibres of the SLN, knowing in this way the
      functional components of this nerve. The study has been developed in 11 adult
      male Sprague-Dawley rats, applying the BDA into the damaged SLN. The results
      obtained in all the animals shown that the rat SLN carries efferent fibres
      originated within the ipsilateral nucleus ambiguous (NA) and dorsal nucleus of
      the vagus (DNV), and that afferent fibres reach the tractus solitari and the
      nucleus tractus solitari. So, in the rat, the SLN seems to convey efferent fibres
      from the NA and DNV and, probably, all the laryngeal afferent fibres.

PMID- 17036990
TI  - [Sensorineural hearing loss in cerebral palsy patients].
AB  - INTRODUCTION: Cerebral palsy (CP) is the most common chronic motor disorder in
      children and frequently associates sensorial pathology. The objective of our
      study was to establish the prevalence and characteristics of sensorineural
      hearing loss in children with CP. METHODS: We performed a retrospective study of
      patients born between the years 1975 and 2004, diagnosed of CP in the "Marques de
      Valdecilla" University Hospital. Clinical data were collected including the
      presence of sensorineural hearing loss, age at diagnosis, treatment and
      associated pathology. RESULTS: Sixty four patients had confirmed CP. Audiological
      testing had been performed in thirty patients (47%) of them 18 (60%) had
      sensorineural hearing loss (12 bilateral and 6 unilateral). In thirteen cases
      hearing loss was associated with mental retardation. The age at diagnosis ranged
      from 3 months to 7 years (mean 23.2 months). Eight patients were treated with
      hearing aids and one with a cochlear implant. CONCLUSIONS: Sensorineural hearing
      loss is frequent in CP patients. Management of this problem is difficult in this
      setting because of the motor disorder and the associated pathology. Early
      audiological assessment is very important to improve the language outcome in
      these children.

PMID- 17036991
TI  - [Assessment of hyperacusis: the self-rating questionnaire on hypersensitivity to
      sound].
AB  - BACKGROUND: Hyperacusis is a decreased sound tolerance. The audiological
      examination includes the loudness discomfort level measurement and the handicap
      evaluation, so we introduce the Spanish validation of the german sound
      intolerance questionnaire. OBJECTIVES: To update the concept of hyperacusis and
      to evaluate its handicap through a Spanish validation of the
      Gerauschuberempfindlichkeit (GUF). PATIENTS: Forty patients referred to our
      Tinnitus and Hyperacusis Clinic in the University Hospital, between October 2004
      and February 2005. OUTCOME MEASURES: The Spanish version of the GUF was performed
      after transla-tion and retro-translation. Internal consistency and reliability
      were established. RESULTS: Spanish adaptation of the GUF and its subscales
      (cognitive, somatic behaviour and emotional reaction) showed a high reliability
      and internal consistency (Cronbach's alfa: 0.9007). Higher GUF scores were
      statistically demonstrated in hyperacusis patients with hearing loss (p < 0.05)
      or tinnitus (p < 0.05). CONCLUSIONS: Spanish adaptation of the GUF is valid,
      reliable and can be used in a clinical setting to quantify the impact of
      hyperacusis on patient's quality of life.

PMID- 17036992
TI  - [Sentinel lymph node in tumors of the larynx: technique and results].
AB  - OBJECTIVES: To evaluate the applicability of sentinel node biopsy in NO
      carcinomas of the larynx. MATERIALS AND METHODS: We carried out a prospective
      study in 19 patients with carcinoma of the larynx NO. We peritumorally infiltrate
      with 1 mCi 99mTc-labeled nanocolloidal albumin via rigid endoscopy in general
      anaesthesia. Sentinel node detection is performed with a gamma sonda during lymph
      node detection. The histological results of the sentinel node are compared with
      the excised neck dissection specimen. RESULTS: Identification of sentinel node
      was successful in 17 patients (89.47%). In 11 patients the sentinel node was
      tumor negative reflecting the correct neck lymph node status (pNO). Three
      patients had metastases in the sentinel node. We observed three false- negative.
      The sensitivity of the technique was 50% (3/6) and the negative predictive value
      78.6%. CONCLUSIONS: We think that more studies are needed to use the technique in
      the laryngeal cancer and that a correct selection of the patients is essential.

PMID- 17036993
TI  - [Comparison of the results obtained through manual and automatic phonetogram].
AB  - INTRODUCTION: The phonetogram (F) is the graphic representation of a person
      phonatory potential. The F carried out with a sonometer and a frequency analyser
      is what is called "manual phonetogram" (MPh), and the one obtained by means of a
      computer is called the "automatic phonetogram" (APh). MATERIAL AND METHODS: We
      have carried out in 12 lyrical singers a standard MPh and an APh with the program
      Dr. Speech Science 3.0. RESULTS: It was showed a significant difference with a p
      < 0.0005 in 14 of the 15 measures compared, and a p < 0.05 for the other one,
      being in general the results of the automatic test different from those of the
      manual in excess, with a correlation between the results obtained through both
      methods. CONCLUSIONS: The APh obtained with the program Dr. Speech Science 3.0 is
      a faster and easier way to obtain the phonetogram than the one used to obtain the
      MPh, showing however big differences in excess compared with the ones of the MPh
      in all the usual phonetometric parameters.

PMID- 17036994
TI  - [Qualitative spectral evaluation of oesophagic voice].
AB  - OBJECTIVES: The aim of the study is to determine the accuracy of acoustic
      spectrography as an outstanding tool in the characterization and monitoring of
      esophageal voice. MATERIAL AND METHODS: Our subjects were comprised of 33
      laryngectomized patients (all male) that underwent qualitative acoustic
      (spectrography of vowel /a/ and a sentence), quantitative acoustic (phonation
      time, fundamental frequency, maximun intensity sound level, speech rate) and
      perceptual protocol. RESULTS: There is a significant statistical relationship
      among Yanagihara-like spectrographic chart classification, psycho-acoustical
      perception and quantitative acoustic parameters. CONCLUSION: We consider that
      acoustic spectrography is an easy, effective method for studying esophageal
      voice, seeking for improving oral communication skills and rehabilitation in the
      laryngectomee population.

PMID- 17036996
TI  - [Ear print as an identification method].
AB  - In recent years, the analysis of earprints has been developed in the field of
      legal and forensic medicine, with the aim of acquiring an identification tool
      similar to fingerprints. In the present paper, we review the current status of
      earprint identification from both a medical and a legal perspective. The
      objective is to introduce an area of knowledge which, is spite of its closeness,
      is not familiar to otolaryngologists, and to present the up to date scientific
      evidence. First, identification in general, and earprint analysis in particular,
      are situated in a historical context. Second, an approximation is made to the
      complexity of earprint analysis, introducing conceptual problems of the method,
      and possible solutions. Next, a discussion on the legal peculiarities of the
      validity of the method is undertaken from the forensic point of view, and
      finally, current development is pointed.

PMID- 17036995
TI  - [Deep neck infections: etiology, bacteriology and treatment].
AB  - Deep neck infections are dangerous for its potential ease to fascial spread,
      sepsis, and upper airway obstruction. This article reviews 77 cases of deep
      cervical infection, focus on etiological, clinical and therapeutic aspects. The
      most frequent location was the submaxillary area (29%), followed by the
      parapharyngeal space (28%), floor of the mouth (27%) and retropharyngeal (14%)
      spaces. Etiology was dental in 32%; pharyngoamigdalar infection in 27%; foreign
      bodies in 13%. In 22% the cause is unknown. Two or more bacteria were isolated in
      72%, with Streptococcus B haemolytic being the most frequent germ. All patients
      were treated with intravenous broad-spectrum antibiotics. Surgical drainage was
      needed in 54%, and tracheotomy in 18%. Four patients developed mediastinitis, and
      one died as a consequence of it. The incidence of deep neck infections has
      decreased after the itroduction of antibiotics but they still may be lethal
      especially when life-threatening complications occur. Early recognition and
      management are necessary.

PMID- 17036997
TI  - [Auditory neuropathy due to the Q829X mutation in the gene encoding otoferlin
      (OTOF) in an infant screened for newborn hearing impairment].
AB  - We report an infant with auditory neuropathy secondary to the Q829X mutation in
      the gene encoding otoferlin (OTOF). Included in a universal newborn hearing
      screening program, the subject passed the otoacoustic emission (OAEs) test. Given
      that the infant had a familial history of deafness auditory brainstem response
      (ABR) testing was performed, revealing a profound hearing impairment. The genetic
      study confirmed that the subject was homozygous for the Q829X mutation in OTOF.
      The patient underwent a cochlear implant, obtaining satisfactory results. The
      moderately high prevalence of this mutation in the Spanish population could
      produce a significant false negative rate in newborn hearing screening programs
      using OAEs.

PMID- 17036998
TI  - [Temporal bone chondroblastoma. A clinical case and literature review].
AB  - We report a clinical case of a 31 year old male with a left temporal painful mass
      of six months evolution. After radiologic diagnosis, intraoperatory biopsy and
      surgical removal, the anatomopathological result confirmed the histology of
      chondroblatoma, with a satisfactory postoperative evolution. The chondroblastoma
      is a benign bone tumor typically located in the epiphysis of long bones and the
      temporal bone is an excepcional location as we have verified through a literature
      review.

PMID- 17036999
TI  - Translational medicine in ultra-long injectable opioid drug discovery--when abuse
      liability and toxicity meet analgesic efficacy.

PMID- 17037000
TI  - Correlations between patient-controlled epidural analgesia requirements and
      individual characteristics among gynecologic patients.
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) has been used widely to
      relieve postoperative pain. Although many studies have demonstrated the safety
      and effectiveness of PCEA, the relationship between patients' characteristics and
      requirements of PCEA has not been investigated yet. We conducted this
      retrospective study to explore the correlations between total PCEA demand and
      patients' characteristics. METHODS: We collected data from patients aged from 20
      to 65, receiving gynecologic operations and consenting to epidural analgesia. All
      patients used postoperative PCEA for at least 3 days. An analgesic solution of
      bupivacaine (0.0625%) and morphine (0.02 mg/mL) was prepared for PCEA in all
      patients. The total PCEA consumption was recorded at the end of the 3-day course.
      Stepwise regression analysis was conducted to sort out influential factors which
      could determine the total PCEA demand. RESULTS: There were 170 patients (81
      benign and 89 malignant cases) included in the analysis. Significant differences
      existed in age and total PCEA requirement between different disease patterns. The
      stepwise regression model selection showed that disease patterns, body mass index
      (BMI) and age were most significant determinants of total PCEA demand. The R and
      adjusted R square values of the final selected model are 0.339 and 0.099,
      respectively. The comparison between the standardized regression coefficient of
      BMI and age suggested that the influence of BMI is greater than that of age.
      CONCLUSIONS: Disease patterns, BMI and age are associated with total PCEA
      requirements. Gynecologic patients receiving procedures for malignant diseases
      consumed more PCEA solution than benign cases. Height is not associated with
      total PCEA demand. There is a close correlation between BMI and PCEA consumption
      but age is a negative correlate.

PMID- 17037001
TI  - Nitric oxide scavenger carboxy-PTIO reduces infarct volume following permanent
      focal ischemia.
AB  - BACKGROUND: Nitric oxide (NO) has been shown to play a dual role as a
      neuroprotectant and a neurotoxin in cerebral ischemia. Free radical scavengers
      protect brain tissue from ischemic injury. Consequently, we examined the
      neuroprotective action of NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), in cerebral ischemia
      induced by permanent middle cerebral artery occlusion (MCAO) in rats and mice.
      METHODS: All experiments were performed in a randomized fashion. In the first
      series of experiments, adult Sprague-Dawley rats (n = 31) subjected to permanent
      MCAO were treated with carboxy-PTIO (0.3, 0.6 mg/kg) or vehicle (normal saline)
      injected intraperitoneally (IP) 1 hr before permanent MCAO. In the second series
      of experiments, adult C57BL/6NCrj mice (n = 49) were treated with carboxy-PTIO
      (0.6, 1.2 mg/kg) or vehicle saline 30 min following MCAO. Neurobehavioral scores
      were determined 22-24 hr following permanent MCAO and infarct volumes determined
      by quantitative image analysis of 2, 3, 5-triphenyltetrazolium (TTC)-stained
      brain sections. RESULTS: Pre-treatment with carboxy-PTIO at 0.6 mg/kg IP in rats
      significantly attenuated infarct volume (19.9 +/- 2.9%; n = 10) as compared with
      vehicle-treated controls (29.2 +/- 2.7%; n = 16), but not at 0.3 mg/kg (28.3 +/-
      8.4%; n = 5). Post-MCAO treatment in mice with 0.6 mg/kg carboxy-PTIO (30.3 +/-
      3.9%; n = 16) significantly attenuated infarct volume as compared with vehicle
      treated controls (46.1 +/- 2.8%; n = 18). CONCLUSIONS: These data demonstrate
      that NO scavenger, carboxy-PTIO, provides significant ischemic neuroprotection
      when given as a pre-treatment as well as after the onset of permanent focal
      ischemia in two animal species.

PMID- 17037002
TI  - Pain intensity and barometric pressure closely correlate in Southern Taiwan.
AB  - BACKGROUND: Previous reports suggest that weather changes may affect the attack
      and pattern of pain. However, a direct relationship between weather and pain
      attack is yet to be determined, especially when very limited data are currently
      available in the tropical or subtropical regions. METHODS: We studied the
      patients who visited our clinic for pain management in Tainan, a city in southern
      Taiwan, in the space from February 2004 to December 2005. Intensity of pain
      measured by visual analogue scale (VAS) and the weather conditions including
      temperature, barometric pressure, humidity and wind speed at the time of
      measurement, were recorded. RESULTS: Our results indicate that higher scores of
      the VAS were associated with older age and lower barometric pressure, while the
      associations with temperature, humidity and wind speed were not statistically
      significant. CONCLUSIONS: Our results demonstrate a unique pattern of pain, which
      varies with barometric pressure, in the subtropical region and may provide
      reference for better pain intervention during change of weather.

PMID- 17037003
TI  - Comparison of intravenous patient-controlled analgesia with buprenorphine versus
      morphine after lumbar spinal fusion--a prospective randomized clinical trial.
AB  - BACKGROUND: Opioid-based patient-controlled analgesia (PCA) has been used widely
      and effectively after spine surgery. The untoward effects of intravenous opioids
      could vary with the drug and dose applied. Buprenorphine, a partial opioid
      agonist, might be devoid of the adverse effects which the traditional opioids
      have. We conducted this prospective randomized clinical trial to evaluate the
      efficacy and safety of buprenorphine for intravenous PCA after spine surgery.
      METHODS: Fifty patients undergoing elective lumbar spinal fusion were randomly
      assigned to either buprenorphine or morphine group. PCA was administered in a
      double-blind manner for a 2-day postoperative course. The evaluation was
      initiated after patients were transferred to the post-anesthetic care unit. Pain
      assessment with visual analog scale (VAS) at rest and after pain elicitation by
      sitting was carried out and recorded at 6, 24, 48 hrs after surgery. Untoward
      effects were also collected. RESULTS: Twenty-five patients were randomized to
      each group. One patient in the buprenorphine group dropped out from the study due
      to dizziness. There was no difference between the groups with respect to the
      baseline variables. The VAS scores at rest and after elicitation of pain by
      sitting showed no difference between both groups. The delivered volume of
      buprenorphine, the numbers of demand and delivery, and the demand/delivery ratio
      were higher in buprenorphine than morphine group at 6 hr after surgery but were
      not different later. No major complications occurred in both groups. The pruritus
      incidence in buprenorphine group was significantly lower than in morphine group
      (0 vs. 24%, P = 0.02). Other adverse effects were similar in both groups.
      CONCLUSIONS: Both buprenorphine and morphine by intravenous PCA provided adequate
      pain relief after posterior lumbar spinal fusion. The incidences of side effects
      were similar in both groups except for pruritus which did not appear in
      buprenorphine group. Buprenorphine was as efficient as morphine and safe for
      intravenous PCA after spine surgery.

PMID- 17037004
TI  - The depot of buprenorphine decanoate produced a dose-related long-lasting
      antinociceptive effect in guinea pigs.
AB  - BACKGROUND: A long-acting analgesic may be particularly desirable in patients
      suffering from long-lasting pain. The aim of the study was to evaluate the
      antinociceptive effect of a novel depot of buprenorphine decanoate and its
      metabolic profiles in human and animal blood. METHODS: Following their
      intramuscular injections in guinea pigs, the antinociceptive effects of the novel
      depot of buprenorphine decanoate (in oil) and the traditional dosage form of
      buprenorphine HCl (in saline) were evaluated. An in vitro metabolic study of
      buprenorphine decanoate in human and animal blood was also carried out. The
      antinociception of drugs was evaluated using the plantar test. The blood
      concentrations of drugs were assayed using a high performance liquid
      chromatography. RESULTS: We found that both the buprenorphine HCl (in saline) and
      buprenorphine decanoate (in oil) produced dose-related antinociceptive effect but
      of different duration of action. Under an equi-mole basis of 0.6 micromol/kg, the
      durations of action of buprenorphine HCl and decanoate were 4 and 72 h,
      respectively. In in vitro metabolic study in human and animal bloods,
      buprenorphine decanoate was totally converted to buprenorphine. Buprenorphine
      decanoate is a prodrug of buprenorphine. CONCLUSIONS: Intramuscular injection of
      the depot of buprenorphine decanoate in guinea pigs produced a dose-related long
      lasting antinociceptive effect which was much longer than that of the traditional
      dosage form of buprenorphine HCl. Moreover, buprenorphine decanoate is a prodrug
      of buprenorphine.

PMID- 17037005
TI  - The use of rocuronium and sevoflurane in acute intermittent porphyria--a case
      report.
AB  - Acute intermittent porphyria (AIP) is an inherited metabolic disorder caused by
      deficiency of porphobilinogen deaminase, an enzyme found in the synthetic pathway
      of heme. Acute attack of AIP may be precipitated by many factors during operation
      and anesthesia, including fasting, dehydration, stress, infection, and drugs.
      Acute attack of AIP is likely fatal. Therefore, the drugs recommended as being
      safe in anesthesia for porphyria patients are up-to-dately refreshed and
      renovated and the identification of whether a drug is safe or not is based on
      cumulative anecdotal experiences. Here, we report the safe use of rocuronium and
      sevoflurane for long exposure in a patient affected with acute intermittent
      porphyria.

PMID- 17037006
TI  - Combined subdural and epidural block in a case of epidural catheterization for
      postoperative analgesia.
AB  - We report a case of unusual block caused by postoperative epidural analgesia for
      laparotomy in a gynecologic patient in consequence of inadvertent epidural
      catheterization. The clinical manifestation included agitation, spotty
      distribution of analgesia, wide spread of sensory block and loss of motor power.
      The radiological findings suggested a multicompartmental block with the anchorage
      of the catheter tip stretching over the epidural and subdural spaces. The default
      of catheter position was not detected during routine test dose procedure.

PMID- 17037007
TI  - Epidural analgesia masked the diagnosis of femoral neuropathy following renal
      transplantation.
AB  - Kidney transplantation related femoral neuropathy can mimic epidural catheter
      related radiculopathy in clinical presentation. Anesthesiologists should keep
      this possibility in mind when performing epidural anesthesia or analgesia for
      kidney transplantation. We present a 52-year-old male who after undergoing
      cadaveric kidney transplantation under general anesthesia in combination with
      epidural analgesia made possible by catheterization via T11-12 interspace for
      reinforcement of anesthesia and for postoperative patient-controlled epidural
      analgesia (PCEA) sustained sensory disturbance and muscle weakness of the lower
      limbs. These symptoms did not improve after discontinuation of the PCEA. Epidural
      hematoma with secondary radiculopathy was contemplated initially. Serial
      examinations including thoracic-lumbar CT scan, abdominal sonography,
      electromyogram and nerve conduction study were thus performed. The final
      diagnosis turned out to be surgical procedure related femoral neuropathy. We
      believe this is the first instance ever reported about the dilemma in making a
      predicative diagnosis from two conditions near akin in kidney transplantation.
      Accurate diagnosis made through serial image and electrophysiologic studies are
      essential to appropriate management.

PMID- 17037008
TI  - Proper use of phosphodiesterase inhibitors according to the situations.
AB  - We came across a case who because of sustained hypotension with normal cardiac
      output was given amrinone which offered an initial excellent response but showed
      impotency later and its replacement by milrinone dramatically improved the
      hemodynamic status. The ensuing hypotension was thought to be the consequence of
      the use of amrinone which was given to treat hypotension in conjunction with
      fluid therapy; besides, it also induced pulmonary hypertension. Therefore,
      milrinone was given to replace amrinone and was successfully to turn the tide. It
      is our suggestion that if the use of a phosphodiesterase (PDE) inhibitor is
      indicated but its side effects are enhanced to refute its use, the application of
      a different PDE inhibitor should be kept in mind.

PMID- 17037009
TI  - Sevoflurane is safe for anesthetic management in patients with multiple
      sclerosis.
AB  - We report a safe anesthetic management of patients with multiple sclerosis (MS)
      using sevoflurane. A 34-yr-old female patient with a 2-yr history of MS was
      scheduled for gynecological surgery. Anesthesia was induced with propofol and
      fentanyl and maintained with sevoflurane, nitrous oxide, and fentanyl. Vecuronium
      was used for tracheal intubation. The patient showed rapid emergence from
      anesthesia. Exacerbation of symptoms of MS was negative according to the
      neurologic assessment at that time. Postoperative pain was managed mainly with
      continuous venous infusion of fentanyl instead of neural block with local
      anesthetics. Transient fever due to subcutaneous infection of the surgical site
      was observed and topical drainage was required. Eventually, postoperative
      exacerbation of symptoms of MS compared with preoperative status did not appear.
      In conclusion, sevoflurane does not induce exacerbation of symptoms and
      facilitates early postoperative neurologic assessment, therefore, it is one of
      ideal anesthetics for MS patients.

PMID- 17037010
TI  - [The value of multislice spiral CT in the diagnosis and staging of laryngeal
      carcinoma].
AB  - OBJECTIVE: To our knowledge, no date are available comparing the impact of
      multislice spiral CT, and multiplanar reconstruction (MPR) and Virtual endoscopy
      (VE) on pretherapeutic staging accuracy. The purpose of our study was to
      determine which imaging should be used as an adjunct to other clinical
      examinations in the pretherapeutic diagnosis and staging of laryngeal carcinoma.
      METHOD: Thirty-two patients with laryngeal carcinoma who were treated surgically,
      were prospectively underwent by contrast-enhanced multislice spiral CT, and MPR
      and VE were subsequently done. CT slice thickness 5 mm, table feed was 5 mm, and
      100 ml of intravenous contrast material was administered at a flow of 3.0 ml/s.
      Two radiologists evaluated axial image and the combined image, the results were
      studied in a blind way. UICCTNM stages were determined by the axial image
      findings and the combined image findings of axial image, MPR, and VE, were
      compared and correlated with postoperative pathology and microlaryngoscopy.
      RESULT: In the evaluation of the neoplastic invasion of ventricular fold, vocal
      cord, the anterior commissure, subglottic region,paraglottic space (PGS), pre
      epiglottic space (PES), thyroid cartilage, and tissue beyond the larynx, the
      combined images were better than axial images in accuracy (98.3% vs 91.3%, P <
      0.01); The accuracy of the combined images staging was 81.3% and the accuracy of
      axial image staging was 93.8%, the difference was not statistically significant
      (P > 0.05). CONCLUSION: Axial image combined with subsequent MPR and VE could
      improve the diagnosis in the evaluation of the neoplastic invasion, neither axial
      image or the combined images could significantly improve pretherapeutic staging
      of laryngeal carcinoma.

PMID- 17037011
TI  - [The value of computed tomography scans of temporal bone and eustachian tubal
      function tests for lesions at tympanic opening of eustachian tube in middle ear
      cholesteatoma].
AB  - OBJECTIVE: To investigate the value of high resolution computed tomography (HRCT)
      of temporal bone and eustachian tubal function tests for lesions at tympanic
      opening of eustachian tube in the patients of otitis media with cholesteatoma
      prior to surgery. METHOD: The clinical data of 38 cases (41 ears) with
      cholesteatoma, which were examined by HRCT scans and eustachian tubal function
      tests before mastoidectomy (29 ears) or mastoidectomy+ tympanoplasty (12 ears),
      were analyzed. RESULT: The rate of conformation between the radiographic and the
      operative findings was 94.1% in the tympanic opening of eustachian tube. We found
      that the rate of the process tissue in the tympanic opening of eustachian tube
      was 86.5% (32/37) during the operation and that they were mainly granulation
      tissues and cholesteatoma. The rate of eustachian tubal hypofunction was 90.2%
      (37/41), the obstructive type and the incompetent type were 32 ears and five
      ears, respectively, only four were normal. CONCLUSION: HRCT scans and eustachian
      tubal function tests by Sonotubometry and Tubotymanoaerodynamic (TTAG) play vital
      roles in diagnosis of the tympanic opening lesion of eustachian tube and in
      assessment of eustachian tubal function pre-operation of middle ear
      cholesteatoma.

PMID- 17037012
TI  - [Analysis of mono-side sternohyoid myo-osteal flap used in reconstruction after
      partial laryngectomy].
AB  - OBJECTIVE: To evaluate the reconstruction effect and to investigate applied
      indication of unilateral sternohyoid muscle flap with hyoid bone in laryngeal
      carcinoma after partial laryngectomy. METHOD: Seventy-three identified cases have
      been analysed by retrospective process. Statistic data mainly include
      postoperative eating condition, decannulation rate and postoperative voice.
      Detailed data of decannulation rate have been contrasted in different clinical
      stages, clinical types and operation types of malignant tumor. More data include
      three year, postoperative complications and so on. RESULT: There are about 79.5%
      cases survived three years or more. All the cases can take food by mouth without
      gastric tube after the operation, 12.9 days in average. The total decannulation
      rate is 76.7% and difference is found between enlarged-vertical hemilaryngectomy
      and the other types of operations. More than 83.6% patients can speak in a nearly
      normal way. CONCLUSION: The decannulation rate, voice and swallowing function are
      all recovered satisfactory after the reconstruction and the decannulation rate is
      not influenced by clinical stage or else of laryngeal carcinoma, but only by the
      range of ectomy. The mono-side sternohyoid muscle flap with hyoid bone can
      restore a baggish defect of larynx, and the survival rate is satisfied. It can
      take the place of full laryngectomy in some T3 or T4 cases whose extent of
      disease laid particular emphasis on one side.

PMID- 17037013
TI  - [Bilateral wedge-shaped cordectomy for treatment of bilateral vocal cord
      paralysis].
AB  - OBJECTIVE: A clinical evaluation of CO2 laser endoscopic bilateral posterior
      wedge-shaped cordectomy (EBPC) in patients with severely compromised airway due
      to bilateral paralysis of the vocal fold. METHOD: The CO2 laser EBPC was
      performed in four cases of bilateral vocal cord paralysis. Follow-up has ranged
      from five months to 36 months. RESULT: Three patients achieved satisfactory
      airway after one laser procedure and one patient received second laser operation
      to manage her posterior webbing. Final voice quality was subjectively good in all
      patients. CONCLUSION: The authors' data confirm the safety, ease of performance,
      and efficiency of the CO2 laser EBPC in patients with bilateral vocal fold
      paralysis. The advantages of the procedure are simplicity in concept, reliability
      of outcome, no need for prophylactic tracheotomy, low risk of complications,
      adequate airway and good voice preservation. CO2 laser endoscopic bilateral
      posterior wedge-shaped cordotomy is an alternative management option for relief
      of upper airway obstruction due to bilateral vocal cord paralysis in abduction.
      The procedure is worthy to apply in clinical use.

PMID- 17037014
TI  - [Vocal sound study in supracricoid partial laryngectomy].
AB  - OBJECTIVE: Vocal sound was studied in 21 patients underwent supracricoid partial
      laryngectomy using Dr. Speech. METHOD: Vocal sound tests and frequency spectrum
      analysis were used in 4 different approaches (CHEP, CHP, TCHEP, TCHP) both before
      and after the operation. RESULT: Vibration pattern of new glottidis formed after
      the four different operation approaches was approximately the same demonstrating
      an augmentation of mucous membrane fluctuation. This vibration pattern were
      increasing and stabilizing gradually with time. CONCLUSION: Retaining on both
      sides and one side in supracricoid partial laryngectomy facilitates restoration
      of vocal function.

PMID- 17037015
TI  - [Cause and treatment of trachea cannula exodus after executed tracheotomy].
AB  - OBJECTIVE: To explore the reason and correct management of trachea cannula exodus
      in the patient who had been executed tracheotomy, and reduce the occurrence of
      trachea cannula exodus and its complication. METHOD: To analysis retrospectively
      23 cases of trachea cannula exodus after executed tracheotomy in patients who had
      been obstructed in upper respiratory. RESULT: In 23 cases of trachea cannula
      exodus, 21 cases were rescued succeeded, 1 case death, 1 case became plant man.
      CONCLUSION: Occurrence of trachea cannula exodus after executed tracheotomy was
      correlated with operative procedure, postoperative care and suitable selection of
      tracheal cannula. Quick-witted ability of doctor and correct management is a key
      that rescued succeeded.

PMID- 17037016
TI  - [Arousal response in child patients in obstructive sleep apnea].
AB  - OBJECTIVE: To analyze arousal response of Polysomnography (PSG) in children with
      obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: Fourty-eight children
      with sleep disorder were studied with 32 guide Polysomnography and analyzed by
      Polysmith. Sleep structure and arousals of preschool-aged and school-aged
      children with OSAHS were compared with those of primary snore patients. RESULT:
      The mean value of AHI of preschool aged children with OSAHS was (10.6+/-8.9) h,
      of AI was (4.0+/-7.1) h, of HI was (6.6+/-4.6) h; The sleep structure between
      OSAHS group and primary snore group was not significant (P > 0.05). The mean
      value of ArI with AHI was (8.2+/-5.9) h, of ArI with LM was (19.6+/-5.8) h, whole
      ArI was 49.3+/-20.4 in preschool-aged children with OSAHS; The mean value of ArI
      with AHI was (7.6+/-6.3) h, of ArI with LM was (14.3+/-7.6) h, whole ArI was
      49.9+/-14.9 in school-aged children with OSAHS. Those of OSAHS children were
      higher than that of primary snore patients (P < 0.05). CONCLUSION: Although OSAHS
      in children is characterized by a restless sleep, the structure is perfect and
      mildly affected by OSAHS. The ArI with AHI, with LM and the whole ArI in OSAHS
      children is higher than those of primary snore patients.

PMID- 17037017
TI  - [The treatment for hypopharynx stenosis using platysma pedicle flap].
AB  - OBJECTIVE: To evaluate the possibility and reliability of platysma pedicle flap
      transfer in the correction of hypopharynx stenosis,and delineate the operation
      skills and clinical results. METHOD: Ten patients with hypopharynx stenosis
      underwent hypopharynx reconstruction using platysma pedicle flap. RESULT: Nine of
      these patients had been decannulated successfully with good airway patency, good
      pronunciation and a good swallow. CONCLUSION: Platysma pedicle flap transfer was
      a single stage reconstruction, relatively simple procedure and less complication
      that can restore an adequate airway and a good swallow. The results indicate that
      the platysma pedicle flap is an ideal transplant for hypopharynx reconstruction.
      This method is simple, safe and reliable.

PMID- 17037018
TI  - [Study on anatomic measurement of oropharynx dimensions between OSAHS and the
      healthy adults].
AB  - OBJECTIVE: One was to study on anatomic measurement of oropharynx dimensions
      between OSAHS and healthy adults, the other was to determine the normal value
      range of the healthy adults oropharyngeal cavity. METHOD: Six anatomic
      measurement of oropharynx dimensions were were measured among 200 healthy adults
      and 93 adult patients with OSAHS,and were compared with that of healthy adults,
      and to determine the normal value range of healthy adults oropharyngeal cavity.
      RESULT: The oropharyngeal cavity size of OSAHS patients and healthy adults were
      significantly different, P <0. 01. CONCLUSION: Nearly all OSAHS patients have
      anatomic obstructive factors at oropharyngeal cavity, The normal valve range of
      the oropharynx size can help to judge the oropharyngeal obstruction of OSAHS
      patients, and to provide the standard date for the operation of UPPP.

PMID- 17037019
TI  - [Clinical analysis of tracheobronchial foreign bodies in children in 1276 cases].
AB  - OBJECTIVE: To investigate the effective therapy methods of foreign bodies in
      respiratory tract to lower its complications and the mortality rate. METHOD:
      Review the anesthesia methods, operation methods and therapeutic efficacy of 1276
      cases of foreign body in respiratory tract and report three cases of death.
      RESULT: Under total intravenous anesthesia we took out foreign bodies by
      bronchoscope in 1197 cases and did that successfully for the first time in 1196
      cases. Under aspiration anesthesia by ether we took out foreign bodies by
      bronchoscope in 78 cases and did that successfully for the first time in 65
      cases, we took foreign bodies for the second time in 12 cases. We carried out
      tracheotomy in three cases. Edema of larynx was found in 12 cases among which 11
      cases were under aspiration anesthesia by ether and one case was under total
      intravenous anesthesia. Under total intravenous anesthesia, the longest time of
      operation was 45 minutes, we could carry out the examination by bronchoscope for
      five times and no edema of larynx was found in all cases. Under aspiration
      anesthesia by ether, the longest time of operation was limited to 5 - 10 minutes,
      we could carry out the examination by bronchoscope for three times at most;
      otherwise, edema of larynx was very severe. Three cases died over apnea.
      Mortality rate is about 0.24%. CONCLUSION: Total intravenous anesthesia combined
      with surface anesthesia of respiratory tract mucosa is the ideal anesthesia
      method for taking out foreign bodies in respiratory tract by bronchoscope. It is
      more dangerous in cases that the foreign bodies are bean or that atelectasis is
      found. We should notice that the less the patients are, the more dangerous the
      operation is. In some cases tracheotomy is needed.

PMID- 17037020
TI  - [The effect of the combined therapy on obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To study the effect of the combined therapy on obstructive sleep apnea
      hypopnea syndrome (OSAHS) with radiofrequency ablation (RFA) and oral appliance
      (OA), and to evaluate the side effect of oral appliances. METHOD: Twenty one
      cases with OSAHS were selected to receive radiofrequency ablation or/and to wear
      oral appliance according to obstructive site. Polysomnography (PSG) was used
      before and after 3 months of treatment to evaluate the therapeutic effect. We
      analyzed the lateral cephalogram and dental casts before initiating treatment and
      after 14 - 24 months of treatment. RESULT: PSG studies confirmed improved
      breathing parameters with the combined therapy. No skeletal changes in the
      position of the mandible were noted, a alteration in the occlusion was found for
      lifelong OSAHS treatment with an OA. CONCLUSION: This combined therapy is
      effective for OSAHS, regular dental follow up visits are necessary when lifelong
      OSAHS treatment with an OA is being considered for patients with OSAHS.

PMID- 17037021
TI  - [Clinical study of tracheotomies children with juvenile onset recurrent
      respiratory papillomatosis].
AB  - OBJECTIVE: To analysis the clinical characteristics of tracheotomies children
      with Juvenile-onset recurrent respiratory papillomatosis (JORRP) and to discuss
      the time of decannulation. METHOD: Thirty-one children with JORRP, who underwent
      tracheotomy and treated with CO2 laser in Otorhinolaryngology department of
      Tongren Hospital between 1993 and 2005, were reviewed in this essay. We analysis
      the age, the site of intratracheal papilloma, invasion fashion of lesion, et al.
      RESULT: Thirty-one tracheotomies children underwent 32 tracheotomy, 20 cases was
      decannulated. Among the 32 tracheotomies cases, three cases were decannulated in
      1 month post operation and the intratracheal lesions were not found. There were
      presented intratracheal lesions in 29 cases. Intratracheal lesions were not
      presented in 20 cases after three months of decannulation. CONCLUSION: The
      tracheotomy should strive to be avoided to JORRP patients. If a JORRP patient was
      underwent tracheotomy, he should be decannulated as early as possible. The time
      of decannulation was performed in the operation or post operation when the
      intratracheal lesions was less.

PMID- 17037022
TI  - [Fhit expression and its relationship with apoptosis and prognosis in nasal and
      paranasal sinus carcinomas].
AB  - OBJECTIVE: To assess the protein expression of Fhit and its correlation with
      spontaneous apoptosis, tumor clinicopathological parameters and prognosis in
      nasal and paranasal sinus carcinomas. METHOD: Forty-eight patients with NPSC
      treated by radical operations from 1991 to 2000 were studied retrospectively.
      Patients included 23 female and 25 male ranging in age from 20 to 71 years.
      Spontaneous apoptotic cells were visualized by TUNEL accompanied by HE and PI
      stain. Immunohistochemistry using SP method was used to assess the expression of
      Fhit. RESULT: The loss of expression of Fhit was found in 26 patients (54.17%,
      26/48). Comparing with abutting non-neoplastic tissue, reduced expression of Fhit
      was found in 16 (16/29, 55.17%) patients. The adenoid cystic carcinoma showed
      stronger expression of Fhit than squamous cell carcinomas (P <0.05). The
      expression of Fhit correlated positively with apoptosis index (r = 0.379, P <
      0.01). Patients with positive expression of Fhit had much better prognosis than
      those with abnormal expression (P < 0.05). CONCLUSION: The reduced expression of
      Fhit may be associated with carcinogenesis and prognosis of nasal and paranasal
      sinus carcinomas. It could be the tumor suppressor gene and realize its function
      through accelerating apoptosis in this kind of neoplasm. Fhit expression may
      provide a novel predictive indicator for disease-free survival after surgical
      resection and postoperative radiochemotherapy in nasal and paranasal sinus
      carcinomas.

PMID- 17037023
TI  - [Chemotherapy guidance of the drug sensitivity test in vitro in human laryngeal
      squamous cell carcinoma].
AB  - OBJECTIVE: Consequently, strong emphasis has been placed on finding appropriate
      approach to achieve optimal treatment outcome. This study analyzed the drug
      sensitivity of Hep-2 cells at concentration-dependent and time-dependent in
      vitro. METHOD: Nonradioactive cell counting Kit-8 (Dojindo, Kumamoto, Japan) was
      used to asses growth inhibition of cancer cells by 5-FU, Carboplatin and
      paclitaxel (TXL) against each concentration and exposure time. We selected
      optimal dose and administration regimen through comparing all the cure effect.
      RESULT: The drug sensitivity test data revealed that 5-FU inhibited cell growth
      dependently on concentration and time, that TXL did dependently on time, and that
      Carboplatin did dependently on concentration. CONCLUSION: Dose and administration
      methods both affect the treatment outcomes. So the drug sensitivity test in vitro
      dose provide clinical therapy with the optimal dose and administration regimen.

PMID- 17037024
TI  - Staffing, capacity, and ambulance diversion in emergency departments: United
      States, 2003-04.
AB  - OBJECTIVE: The increased demand for emergency department (ED) services over the
      past decade has resulted in crowding. This report presents estimates of structure
      and process characteristics of hospital EDs related to their capacity to treat
      medical and surgical emergencies. Estimates of EDs experiencing crowded
      conditions are also presented. METHODS: Several facility supplements were added
      to the 2003-04 National Hospital Ambulatory Medical Care Survey (NHAMCS), which
      were completed by hospital staff. NHAMCS samples nonfederal, short-stay, and
      general hospitals in the United States. Of all sample hospitals that operated 24
      hour EDs, 83 percent completed the supplemental questionnaires. Data from 467
      hospitals were weighted to produce national annual estimates of ED
      characteristics. RESULTS: There was an annual average of 4,500 EDs operating in
      the United States during 2003 and 2004. Over one-half of EDs saw less than 20,000
      patients annually, but 1 out of 10 had an annual visit volume of more than 50,000
      patients. Although 16.1 percent of hospitals expanded their ED physical space
      within the last 2 years, approximately one-third of others planned to do so
      within the next 2 years. Most EDs used outside contracts to provide physicians
      (64.7 percent). One-half of EDs in metropolitan statistical areas (MSAs) had more
      than 5 percent of their nursing positions vacant. Of all on-call specialists, the
      services of plastic and hand surgeons were most frequently reported as somewhat
      or very difficult to obtain (49.4 percent). Approximately one-third of U.S.
      hospitals reported going on ambulance diversion sometime in the previous year.
      About 12 percent of hospitals in MSAs reported having spent between 5 and 19
      percent of their operating time in diversion status. Between 40 and 50 percent of
      U.S. hospitals experienced crowded conditions in the ED with almost two-thirds of
      metropolitan EDs experiencing crowding.

PMID- 17037025
TI  - [Experience with surgical treatment of lung cancer].

PMID- 17037026
TI  - [Carcinogenic mechanisms and anticarcinogenesis].

PMID- 17037027
TI  - [Use of hormone-replacement therapy and steroid contraceptives in menopause as an
      oncological and epidemiological problem: is it a risk and/or benefit?].

PMID- 17037028
TI  - [Dose fractionation for increasing the effectiveness of radiotherapy of tumors].

PMID- 17037029
TI  - [Morbidity statistics of breast cancer in Moscow].

PMID- 17037030
TI  - [Distribution of endometrial carcinoma in the city of Ufa (data from the
      Bashkirian Oncology Dispensary)].

PMID- 17037031
TI  - [Immediate and long-term results of plastic reconstruction of soft tissues of the
      head and neck in areas previously treated with surgery for tumor and radiation
      injury].
AB  - The efficiency was studied of vascularized tissue complexes in 346 cancer
      patients with extensive facial injuries to the head and neck who had undergone
      combined treatment. Free microsurgical autotransplantation was carried out in 7
      (2%) patients, deltapectoral graft--151 (44%), sternocleidomastoid myocutaneous
      flap--39 (11%), pectoralis major flap--10 (3%), bi- and tri-lobed flap--55 (16%),
      temporal musculoperiosteal flap--25 (7%), cheek flap--24 (6.9%), thoraco-dorsal
      axillary flap--24 (6.9%), frontal flap--6 (1.7%), free-flap transfer--5 (1.5%).
      Although most vascularized tissue complexes were placed in previously irradiated
      areas, primary engraftment was reported in 249 (72%) patients, while peripheral
      or partial necrosis in distal part of flap- in 97 (28%). Good cosmetic and
      functional results were obtained in 298 (86%) patients who considered themselves
      cured.

PMID- 17037032
TI  - [Esophagoplasty using modified sleeve-type intrathoracic anastomosis].
AB  - Anastomotic leakage due to loosening of sutures is the frequent cause of
      lethality. To prevent such complication, a sleeve-type esophago-enteric and
      esophagogastric anastomosis was used. Its design eliminates the major cause of
      failure--the basic sutures running through the soft muscular wall of the
      esophagus. The new anastomosis was used in ca. 42 patients: Lewis operation (24),
      proximal resection of the stomach and distal thoracic part of the esophagus and
      adjuvant intrapleural esophagoplasty with the distal end of the stomach (8),
      gastrectomy with resection of the distal thoracic part of the esophagus and
      concomitant intrapleural esophagoplasty with small intestine (S.S.Yudin) (10).
      Postoperative complications were reported in 18 patients (42.9%); lethality-
      11.9%. No leaking esophageal anastomosis was registered.

PMID- 17037033
TI  - [Immunogenetic prognosis and long-term results of surgery for gastric cancer].
AB  - A link between HLA allelic variants and long-term results of surgery for gastric
      tumors was established on the basis of a 10-years follow-up of 112 cancer
      patients (stage I-II--37.9, III-IV--62.1%; radical surgery--44.6%). HLA class I
      was studied in a lymphocytotoxic test; HLA class II--gene DRBI specificity using
      polymerase chain reaction of peripheral blood cell DNA. The control group
      included healthy subjects living in the city of Novosibirsk (n = 341). High
      frequency of antigens HLA-B41, -DR1, -DR7 (p < 0.01) co-occurred with HLA-A2, 
      B12, -B13 and -B18 presence (p < 0.05) in breast cancer patients. Clinical
      manifestations of cancer were shown to develop in HLA-A1, -B8, -B15, -DR3 and 
      DR5 carriers at early stages. Tumor development at later stages (III-IV) was
      associated with HLA-A2, -B12, -B17, -B35, -B41 and -DR7. A link was registered
      between lethality rate, on the one hand, and HLA-A3, -B22, and, in particular,
      DR4, on the other, while remission of more than 7-years--with HLA-A11, -B13, -B21
      and -DR5. HLA-B22/DR3 phenotype involved worse prognosis in radically-treated
      patients whereas that of HLA-B8/DR3--a better one.

PMID- 17037034
TI  - [The use of roncoleukin for LAK therapy in ovarian cancer].
AB  - Roncoleukin--recombinant IL-2--was studied with a view to application for LAK
      therapy. Lymph of ductus thoracicus from ovarian cancer patients receiving
      adjuvant autolymphochemotherapy was used as source of lymphocytes. Immunobiologic
      activity of lymphocytes was assayed after 30-minutes incubation with roncoleukin
      and 24- or 48-hours culturing. The investigation established an increase in T
      cell proliferation, autocrine stimulation of IL-2 production, growth of NK-cells
      cytotoxicity, immediate cytotoxic effect on K562 target cells culture and such
      sensitizing effect as roncoleukin's potential to boost its susceptibility to NK
      lysis. LAK-therapy was used as a component of complex treatment of ovarian cancer
      (8). Our method has a future in dealing with the present pathology.

PMID- 17037035
TI  - [Combined radiotherapy and endovascular x-ray therapy for invasive cancer of the
      urinary bladder].
AB  - The data are presented on treatment of 131 patients with transitional cell
      carcinoma of the urinary bladder. Radiotherapy was received by 57, regional
      intraarterial chemotherapy (RIAT)--27. Radiotherapy was combined with RIAT and
      selective hyperglycemia (HG) in 18 cases. Local super high-frequency (SHF)
      hyperthermia was given additionally to another 29 patients. Radiotherapy alone
      was followed by primary clinical cure, a 9.6-months relapse-free period and 3
      months survival (36.8%), mean survival time being 26 months. In the RIAT group,
      these indices were 29.6%, 10.8 mos, 51.9% and 36 mos, respectively. Combination
      of radiotherapy, RIAT and selective HG yielded significantly improved indices:
      complete response--44.4%, relapse-free period--13.6 mos, 3-year survival--66.7%
      and mean survival time--43 mos. After addition of SHF hyperthermia, complete
      response rose to 69.0%, relapse-free period--18.2 mos, 3-year survival--75.8% and
      mean survival time--61 mos. Joint use of radiotherapy, RIAT, HG and SHF
      hyperthermia caused more damage to tumor, stimulated complete response and
      increased 3-year survival and mean survival time.

PMID- 17037036
TI  - [Effectiveness of repeated systematic radiotherapy for generalized prostate
      cancer].
AB  - Examination of 127 patients with generalized prostate cancer established a low
      prophylactic effect of systematic treatment with strontium-39 chloride: it failed
      to alleviate pain in metastatic cancer, nor was it followed by longer mean
      survival. Repeat systematic radiotherapy is not indicated when palliative
      measures such as hormonal therapy, local radiotherapy and chemotherapy are still
      effective.

PMID- 17037037
TI  - [Novel approaches to combination therapy of Hodgkin's disease].
AB  - Data on 668 patients receiving 4-8 cycles of chemotherapy were used to suggest
      the following approach to complex therapy of Hodgkin's disease: devise a
      simplified model for Hodgkin's disease, develop a new modality of chemotherapy,
      demonstrate feasibility of only four chemotherapy cycles in the poor prognosis
      group, partial response as the ultimate goal of chemotherapy as well as the
      importance of subtotal dosage under 26-36 Gy sufficient for irradiation of the
      entire lymphatic collector. Said measures will, in their totality, offer fresh
      opportunities in treatment of Hodgkin's disease.

PMID- 17037038
TI  - [Effect of interleukin-2 on apoptosis and function of human lymphocytes in in
      vitro cytostatics culture].
AB  - In vitro experiments were conducted to determine the impact of interleukin-2 (IL
      2) on apoptosis and function of cytostatic-cultured lymphoid (mononuclear) cells
      (MNC) of peripheral blood from healthy subjects and children with cancer. Neither
      slight or any effect on vepesid-16 or carboplatin--cultured MNC apoptosis, nor
      any phytohemagglutinin--induced proliferation was found. By contrast, in
      carboplatin- cultured MNC from healthy subjects, IL-2 significantly potentiated
      their toxicity for tumor cells by producing interferon-gamma. It was concluded
      that IL-2 predominantly supported MNC functional activity rather than inhibited
      lymphoid MNC apoptosis in in vitro culture with cytostatic drugs.

PMID- 17037039
TI  - [Psychological and immunological defenses in cancer--the two aspects of one
      problem].
AB  - The study group included 17 cancer patients, aged 25-55, (stage III-IV), mostly
      suffering melanoma. All of them received hypnosuggestive therapy to correct
      psycho-emotional disorders. Significant decrease in anxiety-related indices (p <
      0.001) due to therapy pointed to rehabilitation of psychological defenses.
      Clinical rehabilitation was manifested by improved quality of life (p < 0.01),
      better habitus and adaptation (p < 0.01). The modulating effect on the
      macrophageal and phagocytic components of the immune system (p < 0.05) was
      matched by a significant correlation between psychological defense indices and
      those of immunological status. Our data have contributed to the existing
      knowledge about relationships of mind and immunity in cancer patients.

PMID- 17037040
TI  - [Seasonal patterns of breast tumor growth in Far North residents].
AB  - Earlier, we established a relationship between sex hormone receptor concentration
      in tumor and 5-year survival, on the one hand, and seasonality, on the other. The
      parameters showed a distinct 6-month cycle. That pointed to certain environmental
      factors which could synchronize hormone-dependent tumor process in the breast of
      women living in the North. The present study is concerned with a relationship of
      6-month rhythm of tumor growth and latitude of residence. Said rhythm was
      reliably identified as a parameter of 5-year survival in the Far North (68 deg.
      northern latitude, p < 0.001). Maximum values of 5-year survival were registered
      in those diagnosed with cancer in winter or summer, while those diagnosed in
      spring or fall had unfavorable prognosis. Northern magnetic storms recur at 6
      month intervals and most frequently in spring and fall. Electromagnetic radiation
      is known to suppress melatonin production and, that might have stimulated tumor
      process. Therefore, it is most likely that solar electromagnetic radiation might
      synchronize hormone-dependent tumor process in women resident in the North.

PMID- 17037041
TI  - [Antitumor immunity transfer by a factor isolated from lymphocytes of tumor
      bearer].
AB  - Low-molecular extracts (LMEs) of lymphocytes were obtained from spleen of
      noninbred rats using our experimental model of intraorganic growth of Guerin's
      carcinoma. They were intended to transfer immune reaction to tumor antigens in
      vitro. It was LMEs developed prior to tumor progression in spleen that showed
      immunospecific activity with respect to tumor cells. Also, they had marked
      antigen-independent immunopharmacological activity. Single intravenous injection
      of LMEs100 pg given on day 7 of tumor growth stimulated antitumor resistance in
      intact rats within a short time. It prevented tumor cells engrafting in 60% of
      tumors. A tumor-specific factor has been evolved capable of immune reaction
      transfer to tumor antigens in vitro thus preventing tumorigenesis in recipients
      in vivo.

PMID- 17037042
TI  - [Thyroid cancer in male patients].
AB  - Data on 117 male patients with thyroid cancer (1994-2004) have been assessed. It
      was found that thyroid cancer often engenders in the nodular formation it males.
      Early-stage cancers were detected in 63 cases (54.9%). Radiotherapy as a
      component of combined treatment was the most popular modality (43.2%), due to the
      malignant character of locally-advancer tumor. Ten-year survival was in 65.2%,
      while, in 11.9%, radical surgery was not indicated.

PMID- 17037043
TI  - [Endoscopic argon-plasma coagulation and combined radiotherapy for short (up to 3
      cm) esophageal cancers].
AB  - The immediate and 3-year results were evaluated of application of combined
      radiotherapy and/or endoscopic argon-plasma coagulation carried out for
      esophageal cancers 3 cm long or less in 39 patients. Recurrences were reported,
      in 31.4% ca. 4 months later. Joint use of the modalities was followed by an up to
      5-months rise in relapse-free period. Mean survival time was 20.2 months, and it
      was significantly higher in radiation-treated patients without metastases. One
      year survival was 96.6% in those without distant metastases, 2-year--72%, and 3
      year--47.6%. Our data point to new vistas in application of our techniques,
      particularly, for short (up to 3 cm) inoperable esophageal cancers.

PMID- 17037044
TI  - [Multiple endocrine neoplasia syndrome].

PMID- 17037045
TI  - [Polyphasic evidence for the transfer of Promicromonospora yunnanensis to
      Cellulosimicrobium cellulans].
AB  - Polyphasic taxonomic investigations of Promicromonospora yunnanensis AS4.1333
      deposited in the China General Microbiological Culture Collection Center (CGMCC)
      indicated that strain AS4.1333 was closely related to Cellulosimicrobium
      cellulans DSM43879(T), the two organisms shared a 16S rRNA gene similarity of
      99.6% which correspond to 5 nt differences at 1423 positions. Corresponding DNA
      DNA reassociation value was 89.3%, significantly higher than 70% cut-off point
      recommended for the delineation of genomic species by Wayne et al. (1987).
      Results of chemotaxonomic analyses of cell wall (Whole-organism hydrolysates were
      rich in rhamnose, fucose and galactose; peptidoglycan type A4a), mycolic acids
      (One dimensional TLC of whole-organism acid methanolysates revealed the absence
      of a lower spot (Rf value around 0.47) that corresponded to mycolic acids),
      principal menaquinones (MK-9 (H4)), phospholipid type (PV) and the G + C content
      of the DNA (73.8 mol%) supported the conclusions of the genotypic analyses. The
      very similar morphological and physiological characteristics agreed with the high
      degree of relatedness. On the basis of phylogenetic analyses based on the almost
      complete 16S rRNA gene sequence, DNA-DNA reassociation values, chemotaxonomic
      properties, morphological and physiological characteristics, it is concluded that
      strain AS4.1333 should be removed from the genus Promicromonospora, and strain
      AS4.1333 and Cellulosimicrobium cellulans should be considered to be a single
      species. Promicromonospora yunnanensis AS4.1333 was proposed to transfer into
      Cellulosimicrobium cellulans. The type strain remains DSM43879T.

PMID- 17037046
TI  - [Isolation and characterization of a new Pseudomonas strain against Phytophthora
      capsici].
AB  - One Pseudomonas strain GP72, which was against Phytophthora capsici, was isolated
      from green pepper rhizosphere in Jiangsu province. It had distinctively
      inhibitive effect on several kinds of pathogenic fungi; mostly of them are
      soilborne pathogens. Therefore, this strain may be used for an effective
      biocontrol strain in the crop protection. The morphological, biochemical and
      physiological characteristics, Biolog GN, G + C mol% content and 16S rDNA
      sequence analysis of this strain were studied. In comparison and conclusion of
      all the experimental data, GP72 is identified as Pseudomonas chlororaphis. The
      strain is single-cellular and motile by means of single polar flagellum. It was
      not able to accumulate ploy-beta-hydroxybutyrate. Compared to P. aureofaciens 30
      84, the strain was able to survive at the concentration of 5% NaCl. It could
      strongly utilize 45 of 95 carbon-substrates; weakly utilize 6 of the whole carbon
      substrates and never utilize 43 of the whole carbon-substrates resulting from
      analysis of Biolog GN, bearing the similarity probability of 98% with Pseudomonas
      chlororaphis and with the similarity index 0.72. The G + C content of the strain
      DNA was 65.1 mol% using the thermal denaturation method. A phylogenetic tree was
      constructed by comparing with the validly published 16S rDNA sequences of the
      related type strains from GenBank, using the Neighbor-Joining method of Saitou
      and Nei and the Clustal X program to do the multiple alignments. The tree
      topology was tested by a bootstrap analysis of 1000 samplings. The overall
      similarity value between strain GP72 and typical is the closest in the
      phylogenetic tree. For the latest taxonomical development has put genus
      Pseudomonas aureofaciens to the genus Pseudomonas chlororaphis, then it is
      appropriate to say that GP72 belongs to the genus Pseudomonas chlororaphis. This
      is the first time in China to report that a strain of Pseudomonas chlororaphis
      was isolated from green pepper rhizosphere, having a strong inhibitive effect on
      Phytophthora capsici and other soilborne pathogenic fungus. The other
      characteristics and the biocontrol mechanism are yet to be further studied.

PMID- 17037047
TI  - [Molecular identification and genetic diversity in Konnyaku's soft rot bacteria].
AB  - The soft rot bacteria Erwinia are an important pathogens of konnyaku and other
      ornamental plants. Thirty-three strains were isolated from soft-rotted konnyaku
      and other ornamental plants. According to the characteristics of pathogenicity
      and culture character on semi selective medium (crystal violet pectate, CVP),
      most of strains tested caused rotten symptom in tubers and stems of konnyaku, and
      characteristic deep cavities were formed on CVP. To amplify 16S-23S rDNA
      intergenic transcribed spacer( ITS) by PCR and electrophorese through agarose
      gel, most strains are clustered into two heterogeneous populations of Erwinia
      carotovora subsp. carotovora, E.c.c. and Erwinia chrysanthemi, E. ch.. Besides,
      several other strains could not be identified into species by ITS-PCR. The
      characteristic band patterns of E.c.c. and E.ch. could be clearly distinguished
      by repetitive element-polymerase chain reaction (rep-PCR,BOX and J3 primers). And
      the fingerprinting of E.c.c. stains were also different from each other.
      Dendrogram was generated from the data of primer BOX by using UPGMA analysis
      because the primer BOX was higher resolution than other primers (such as prime
      J3) for identifying the same intraspecies strains. Strains of E.c.c. were divided
      into five groups on the 0.1 level of linkage distance.

PMID- 17037048
TI  - [Construction of the shuttle expression-secretion vector with the promoters and
      signal peptide-encoding sequence from Brevibacillus brevis].
AB  - The multiple and tandem promoters and signal peptide-encoding sequence of cell
      wall protein encoding gene was amplified from Brevibacillus brevis B15 total DNA,
      the PCR fragment was cloned, sequenced and analyzed, then was submitted to
      GenBank with a Accession No. AY956423. Another pair of primers were designed to
      amplify the fragment again, BamHI and Pstl sites was introduced flanking the PCR
      production. BamHI/Pstl digested fragment was cloned into the corresponding site
      of shuttle vector pP43NMK to generate the expression-secretion vector pP15MK. The
      inserted fragment was upstream of mpd gene and the signal peptide-encoding
      sequence was fused in frame with the mpd gene, which its own signal peptide
      encoding sequence was deleted. The recombinant vector was transformed into
      Bacillus subtilis 1A751, under the control of the promoters and signal peptide
      from Brevibacillus brevis B15, mpd gene was continuously expressed and secreted
      at a high efficiency throughout the exponential growth phase and into the late
      stationary phase, the expression production methyl parathion hydrolase (MPH) was
      attached on the outside of the cell membrane. MPH activity accumulated to a
      maximum level of 7.79 U/mL after 48 h of cultivation at the late stationary
      phase, which was 8.1-fold higher than the expression level of the original
      Plesiomonas strain M6.

PMID- 17037049
TI  - [Analysis of mechanism and relationship of GacA and RsmA, two regulators of
      antibiotics production in Pseudomonas sp. M18].
AB  - In previous study, it has already been confirmed that the wild type strain of
      Pseudomonas sp. M18 isolated from the agricultural soil can produce two
      antifungal agents phenazine-1-carboxylic acid (PCA) and pyoluteorin (Plt).
      Biosynthesis and secretion of these secondary metabolites contribute to its
      biological control and suppression of soilborne pathogenic fungi. As main
      regulators, GacA and RsmA differentially exert global regulation on production of
      PCA and Plt, respectively. In order to study the regulatory mechanism of
      secondary metabolites production in Pseudomonas sp. M18, a gacArsmA double
      mutant, designated as M18GR, was constructed with insertional mutation. Then, the
      mutant M18G, M18R, M18GR and the wild type strain M18 were inoculated into PPM or
      King's medium B (KMB), respectively. During cultivation of strain M18 and its
      derivatives, their PCA and Pit were respectively detected with High Performance
      Liquid Chromatography (HPLC). The results showed that PCA production in the
      mutant M18GR was lower than that in the mutant M18G and higher than that in the
      mutant M18R. Plt production in the mutant M18GR was, however, much less than that
      in the mutant M18R and much more than that in the strain M18 and the mutant M18G.
      With these observations, it is tempting to suggest that biosynthesis of PCA and
      Plt regulated by GacA or RsmA seem to occur at posttranscriptional level, not at
      transcriptional level. This regulation on secondary metabolites seems to be
      indirectly mediated by other unknown factors. Meanwhile, based on the
      construction of two translational fusions, gacA'-'lacZ and rsmA'-'lacZ, the assay
      of beta-galactosidase activities in KMB medium indicated that both GacA and RsmA
      did not have autoinduction of their own gene expression, respectively. Although
      GacA did not influence expression of the rsmA gene, RsmA could exert some
      positive influence on the gacA gene expression in Pseudomonas sp. M18.

PMID- 17037050
TI  - [Screen and identification of Streptocococcus pneumoniae genes specifically
      induced in host].
AB  - To identify in vivo-induced genes of S. pneumoniae and search new potential drug
      targets and vaccine candidates, a selection system was developed based on the in
      vivo expression technology (IVET). Promoter galU gene which is critical for the
      capsular polysaccharide biosynthesis and lacZY gene which encodes bea
      galactosidase were employed as dual reporter genes. The galU-deficient mutant of
      S. pneumoniae is incapable of utilizing galactose and synthesizing capsular
      polysaccharide, therefore can't survival in the host. Firstly, the random pieces
      of S. pneumoniae chromosomal DNA (200-500 bp), obtained by partial Sau3Al
      restriction digestion, were subcloned into the Bgl II site of pEVP3-galU.
      Transformation by this plasmid library yielded promoter-trap library in S.
      pneumoniae. Then, the library was used to infect animals. Bacteria were harvested
      from lung tissue. White clones on TSA agar containing X-gal were used to reinfect
      animals. The sequence of infection and sorting was performed twice, 165 white
      clones harvested from the final round of infection were analyzed. A total of 15
      unique sequences were obtained through in vivo screen. The bioinformatics
      analysis showed that these ivi genes involved in colonization and adherence,
      energy metabolism, nutrient substance transport, transcription regulation, DNA
      metabolism and cell wall synthesis. And there were some hypothetical proteins
      have unknown functions. Part of these genes may be related with virulence and can
      be used as vaccine candidates and drug targets.

PMID- 17037051
TI  - [Biological significance of amino acids deletion in NA stalk of H5N1 avian
      influenza virus].
AB  - It has been reported that NA gene of some H1N1 Influenza A virus strains isolated
      since 1933 is characterized by a deletion of 11 to 16 amino acids in the stalk.
      The spontaneous mutant in NA stalk of H1N1 virus lacks enzyme activity with large
      substrate (fetuin) but not with small substrate (sialyllactose). Recently, H5N1
      virus also has been found that NA has the same unique mutation in the stalk, a
      deletion of 15 to 20 amino acids. However, biological significance of this
      mutation has not yet been reported. In order to investigate biological
      significance of the amino acids deletion in NA stalk of H5N1, five reassorted
      H5N1/PR8 viruses were generated via eight-plasmid based reverse genetics system.
      These five viruses were named 506, m506-, 646, m646+ and 196, respectively. The
      six internal genes of recombinants were all from A/PR8/34(H1N1), and HA gene was
      from A/G/JS/03(H5N1), however, they had different NA genes. 506 and m506- held NA
      fragments derived from A/G/HD/00(H5N1), and the former was distinguished with a
      longer NA which had no 20 amino acids deletion in the stalk. 646 and m646+ held
      NA fragments from A/G/JS/03(H5N1), and the NA stalk of m646+ was 20 amino acids
      longer than that of 646. The NA of 196 was derived from A/PR8/34 which had 15
      amino acids deletion in its stalk. Biological characteristics of these viruses
      showed that recombinants with different NA length could grow well in embryonated
      SPF eggs, and their EID50, MDT, and viral titers were similar. However, the
      length of NA was related to the capacity of eluting viruses from erythrocytes for
      506 and 646+ which holding longer NA stalks eluted from erythrocytes more quickly
      than m506-, 646 and 196 did. Moreover, 15 or 20 amino acids deletion in NA stalk
      had a pronounced effect on virus growth ability in MDCK cells. Viral titers in
      supernatant of MDCK infected with m506- or 646 were 10 to 100 folds higher than
      those infected by 506 or m646+. And the plaque size of m506- and 646 were larger
      than that of 506 and m646+. The results reveals that H5N1 AIV with amino acids
      deletion in NA stalk would expand its host range. The unique amino acids deletion
      in NA molecule of H5N1 may be associated with the adaptation of virus to
      terrestrial poultry or the increasing ability of interspecies transmission.

PMID- 17037052
TI  - [Rescue of a recombinant Newcastle disease virus expressing the green fluorescent
      protein].
AB  - A recombinant Newcastle disease virus (NDV) expressing the green fluorescent
      protein (GFP) was generated by applying reverse genetics techniques. The GFP open
      reading frame flanked by NDV transcription start and stop sequences was inserted
      between the phosphoprotein (P) and matrix protein (M) in a full-length cDNA clone
      of NDV Lasota vaccine strain. This plasmid transcribing antigenome RNA was
      cotransfected with helper plasmids expressing viral nucleoprotein, phosphoprotein
      and large protein into cells stably expressing T7 RNA polymerase. The rescued
      virus was first propagated in 10-day-old embryonated eggs and the allantoic fluid
      was used to infect primary chicken embryo fibroblasts (CEF) cells. The appearance
      of GFP in live infected cells confirmed further the recovery of a recombinant NDV
      (rNDV-GFP) expressing this reporter gene. Nine successive passages in embryonated
      chicken eggs were performed. Allantoic fluid samples were then titrated by a
      microtiter plate HA test. HA positive ailantoic fluid were used for further egg
      passages. All the allantoic fluid samples were titrated by end point dilutions
      and infected cells were examined for the presence of GFP expression. To analyze
      virus growth, 10-day-old embryonated SPF chicken eggs were inoculated with 1 x
      10(4) EID50 rNDV or rNDV-GFP. At 24,48,72 and 96 h p.i. the allantoic fluid of
      inoculated eggs containing live embryos was harvested and clarified by
      centrifugation. Supernatants were used for titration of EID50 in 10-day-old
      embryonated SPF chicken eggs. rNDV and rNDV-GFP grew to similar titers (10(9)
      EID50/mL). In order to test the virulence of rNDV-GFP, infectious allantoic fluid
      of rNDV-GFP were inoculated into embryonated SPF chicken eggs at 1 x 10(6) EID50.
      No dead embryonated egg was found within 96 hours. The replication kinetics and
      pathogenicity in SPF embryonated eggs of rNDV-GFP did not differ significantly
      from that of the parent virus. LaSota is a widely used NDV live vaccine strain.
      The reverse genetic system established for this LaSota vaccine strain provided a
      useful platform for development of novel live viral vector vaccines in future.

PMID- 17037053
TI  - [Screening of microorganism producing polyunsaturated fatty acids with sugarcane
      molasses].
AB  - A strain name LB1 producing polyunsaturated fatty acids with sugarcane molasses
      was screened form soil samples by the methods of Sudan Black B stain and the
      determination of PUFAs' iodine value. Based on the grass morphological and
      physiological characteristics and the sequence similarity of ribosomal DNA-ITS,
      the strain was identified as Mucor recurvus sp.. The results of L64 (4(3))
      orthogonal experiments indicated when Mucor recurvus was cultivated at 28 degrees
      C for 5 days with 160 r/min, the yields of PUFAs with 10(0) BX sugarcane molasses
      (pH 6.0) were up to 80.49% content of total fatty acids. The total lipids content
      was 57.08% of fermentation biomass, which were composed of 15.42% Oleic acid,
      14.38% Linolenic, 23.55% gamma-Linolenic, 3.06% alpha-Linolenic, 9.87%
      Arachidonic acid, 8.14% Eicosapentaenoic acid, 6.07% Docosahexaenoic acid, etc.

PMID- 17037054
TI  - [Identification of a strain NJ2 hydroxylating imidacloprid and the transformed
      product].
AB  - A strain named NJ2 was isolated from the soils in Nanjing area, and its resting
      cells transformed IMI into a polar product. The strain was identified as
      Stenotrophomonas maltophilia based on BioMerieux Vitek system and the analysis of
      16S rDNA sequence. Mass spectrometry of the product extracted with an organic
      solvent and re-crystallization gave m/z value of 272 for the molecular ion while
      256 for substrate IMI. It demonstrated that the transformed product was the
      hydroxylated derivate of IMI or hydroxy IMI. NMR analysis further indicated that
      the hydroxyl moiety located at the ring of imidazolidine and the transformed
      product was 5-hydroxy IMI. Kinetics of transformation IMI showed that the content
      of IMI decreased 1.15 mmol/L and the content of transformed product 5-hydroxy IMI
      increased 1.10 mmol/L after transformation for 10 days. The molar conversion
      yield was 95.9%. The S. maltophilia NJ2 strain, with the characterization of
      strong transformation ability and high molar conversion yield, can be used in
      industrial production of 5-hydroxy IMI for synthesis of highly insecticidal
      olefin IMI.

PMID- 17037055
TI  - [Alleviative effects of nitric oxide on the biological damage of spirulina
      platensis induced by enhanced ultraviolet-B].
AB  - Continuing depletion of the stratospheric ozone layer by atmospheric pollutants,
      in particular chlorofluorocarbons (CFCs), has resulted in an increasing incidence
      of solar UV-B (280-320 nm) at the Earth's surface. Enhanced UV-B radiation has
      been considered as important global environmental problem and results in
      important effects to mankind and the entire global ecosystem. Nitric oxide (NO)
      is not only a toxic molecule, one of reactive nitrogen species (RNS), but also an
      important redox-active signaling molecule. NO is really a double-edged sword, it
      can be either beneficial and activate defense responses in plants and animals or
      toxic, together with ROS. Besides those, NO can also act as a signal molecule and
      play very important roles in life of organisms. To study the effects of NO on the
      biological specific property of enhanced UV-B stressed Spirulina platensis, the
      chlorophyll-a, protein contents and biomass were investigated under enhanced UV-B
      radiation and its combination with different chemical treatment. The changes of
      chlorophyll-a, protein contents and biomass confirmed that 0.5 mmol/L sodium
      nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the
      biological damage of cyanobacteria-Spirulina platensis 794 caused by enhanced
      ultraviolet-B. Further results proved that NO significantly increase the content
      of protein and proline. Meanwhile, the accumulation of reduced glutathione (GSH)
      in S. platensis cells were raised under normal growth condition. But exogenous NO
      could decrease the increasing of reduced glutathione (GSH) in enhanced UV-B
      stressed S. platensis cells. These results suggest that NO has protective effect
      and can strongly alleviate biological damage caused by UV-B stress in S.
      platensis 794 cells. For the first time, reported the effect of NO on the
      regulating ability of biological damage of S. platensis induced by enhanced UV-B.
      Therefore, further investigations will be necessary to inquire into the
      interaction and inter-correlation of signal molecules and the mechanism in
      cyanobacterium under enhanced UV-B stress.

PMID- 17037056
TI  - [Cloning, expression and purification of D-carbamoylase from Sinorhizobium
      morelens S-5].
AB  - A N-carbamoyl-D-amino acid amidohydrolase gene (hyuC) from Sinorhizobium morelens
      S-5 was cloned by LA PCR, and its nucleotide sequence was determined. The deduced
      amino acid sequence encoded by the hyuC gene exhibited high homology to the amino
      acid sequences of D-carbamoylase from other sources. The gene could be highly
      expressed in Escherichia coli, and the recombinant enzyme was purified 16.1-fold
      to homogeneity with a yield of 21.2% by heat treatment and three steps of column
      chromatography. The results of gel filtration on Superdex 200 HR and SDS
      polyacrylamide gel electrophoresis suggested that the enzyme was a tetramer
      protein of identical 38-kDa subunits. The recombinant enzyme catalyzed the
      hydrolysis of N-carbamoyl alpha-amino acid to the corresponding free amino acid,
      and it was strictly D-specific. The enzyme showed broad substrate specificity,
      and exhibited high activity in the hydrolysis of N-carbamoyl-D-p
      hydroxyphenylglycine as substrate. The enzyme did not hydrolyze N-carbamoyl-beta
      alanine. The optimum pH and temperature of the enzyme were pH 7.0 and 60 degrees
      C, respectively. Enzyme activity was slightly improved by Ca2+ and Fe2+, and
      nearly not affected by metal chelators and sulfhydryl reagents. The enzyme showed
      high thermal and oxidative stability. These results show that the enzyme has
      great potential for industrial application.

PMID- 17037057
TI  - [Study on the screening of lactamase and its fermentation conditions].
AB  - (-)-gamma-Lactam is one of the key starting materials for the synthesis (-)
      cabovir and (-)-abacavir, which serve as two powerful antiviral agents. The
      production of gamma-lactam using enzymatic resolution of racemic gamma-lactam was
      attempted in the paper. 20 out of 69 strains capable of producing lactamase were
      screened from soil samples collected in several districts throughout Beijing;
      particularly N-actylphenylalanine was used as sole carbon source in the screening
      method. It was found by chiral HPLC analysis that strain L29-9 was able to
      enantioselectively hydrolyze the (+)-isomer in the racemic lactam, thus giving
      the desired (-)-gamma-lactam with high enantiomeric excess (> 70%). Ferment
      conditions of strain L29-9, including carbon source, nitrogen source, pH, and
      culturing time, were studied and the optimum conditions were as follows: citric
      acid 2 g/L, yeast extract 5 g/L, pH 7.0, culturing for 40h. Biotransformation
      using whole cells of the strain was inducted at 30 degrees C for 12h, giving (-)
      gamma-lactam as enantiopure product with yield up to 40% and 99.5% e.e.

PMID- 17037058
TI  - [Cloning of the gene encoding a thermostable alpha-amylase from bacillus
      licheniformis CICIM B0204 and functional identification of its promoter].
AB  - Thermostable alpha-amylase, catalyzing the hydrolyzation of starch to dextrin,
      maltose and glucose at higher temperature, is one of the most industrial
      important enzymes. Several species of Bacillus have been found and genetic
      improved to produce the thermostable alpha-amylases. In present study, a gene,
      amyL, coding for a thermostable alpha-amylase with its flanking sequences was
      cloned from an industrial Bacillus licheniformis CICIM B0204 by using a
      combination of routine polymerase chain reactions (PCR) and inverse PCR with a
      pair of initial primers derived from the highly conserved region of bacterial
      alpha-amylase genes and the functional identifications of the cloned amyL and the
      activities of its promoter and signal peptide in Escherichia coli were
      investigated. The amyL was composed of 1539 bp with 180 bp at upstream for its
      promoter and 160 bp at downstream for its terminator. The deduced mature peptide
      of the a-amylase was composed of 512 amino acid residues and its signal peptide
      29 amino acid residues at N-terminal. The nucleotide and deduced amino acid
      sequences of amyL were extremely similarity to those from Bacillus species with
      three amino acid residues difference (Arg163-->Leu, Ser339-->Gly, Ala349-->Ser)
      comparison to that from a laboratory strain B. licheniformis 584. Under the
      control of T7 promoter, the structural region of amyL was functionally expressed
      in Escherichia coli. Additionally, the structural region of the gene coding for a
      beta-mannosidase from B. licheniformis CICIM B2004 was inframely inserted into
      the downstream of the promoter and signal sequence of amyL and expressed in E.
      coli. The amyL promoter and signal sequence was functionally directed the
      expression and secretion of the beta-mannosidase in E. coli cells with the
      expression level of 295 U/mL.

PMID- 17037059
TI  - [Cloning and expression of lumbrokinase gene in Pichia pastoris].
AB  - Lumbrokinase gene F238 was amplified by RT-PCR from the total RNA of earthworm
      (Eisenia fetida). The gene including signal peptide sequence was inserted into
      pUCm-T vector to construct pUCm-T-F238. The product was sequenced. The GenBank
      accession number was DQ202401. Lumbrokinase F238 comprised 738bp and included an
      open reading frame that encoded a polypeptide of 245 amino acid residues,
      containing a signal peptide of 7 amino acid residues and a mature peptide of 238
      amino acid residues. Both nucleotide and amino acid sequences homologies were 99%
      after the sequence was compared with Lumbricus rubellus F-III-2. There were two
      base pair mutations, which subsequently caused two amino acid mutations. The
      characteristics and structure of F238 was analysed and predicted with biology
      softwares and databases. The pl of F238 was 4.61. It had eleven Cysteines, which
      formed three disulfide bonds. Its secondary structure mainly consisted of beta
      sheet. Lumbrokinase F238 had serine active center. It was a protease in trypsin
      family of serine protease superfamily. Lumbrokinase gene F238-m without signal
      peptide sequence was obtained by PCR using pUCm-T-F238 as template. The
      expression vector pPIC9-F238-m was constructed by inserting gene F238-m into
      yeast expression and secretion plasmid pPIC9. Plasmid pPIC9-F238-m was linearized
      with BgIII and then transformed into Pichia pastoris strain GS115 cell by
      electroporation method. Phenotypes of transformants were screened in MM and MD
      plates to ensure the integration of lumbrokinase gene F238-m into yeast
      chromosome DNA. Methanol was added to a final concentration of 0.5% for the
      expression of recombination protein every 24h to maintain induction. The result
      of SDS-PAGE showed that the molecular weight of the expression product was about
      28 kDa, in correspondence with the theoretical molecular weight. After the
      induction of expression, the fibrinolytic activity of the supernatant was
      measured using artificial fibrin plates. Then the engineering strain of high
      activity was obtained, and the fibrinolytic activity was up to 100 U/mL.

PMID- 17037060
TI  - [Screening of a low alcohol dehydrogenase activity mutant of rhizopus oryzae and
      the regulation of Zn2+ and Mg2+].
AB  - Ethanol is the main by-product in the fermentation broth of Rhizopus oryzae
      As3.3461 for the production of high-optical purity L-lactic acid. Alcohol
      Dehydrogenase (ADH) is the branch pathway enzyme that catalyzes the
      transformation of ethanol from pyruvate in Rhizopus oryzae, which decreases the
      conversion rate of glucose to L-lactic acid. Thus, screening the mutants with
      lower ADH activity may increase lactate production dramatically. In present
      study, Rhizopus oryzae As3.3461 was mutated with N-methyl-N'-nitro-N
      nitrosoguanidine (NTG), and 21 mutants which showed lower ADH activity were
      isolated with selective medium of Yeast-Peptone-Dextrose (YPD) containing 0.6%
      allyl alcohol (V/V). Compared with other mutants, the 12th mutant strain (named
      as HBF-12) shows the highest conversion rate of L-lactic acid. By contrast with
      Rhizopus oryzae As3.3461, the parent strain, the ethanol production and the ADH
      activity of HBF-12 decrease 73.6% and 76%, respectively. Whereas, the L-lactic
      acid production and the LDH activity of HBF-12 increase 41.2% and 19.6% than
      those of the parent strain, respectively. The activities of ADH and LDH of HBF-12
      were regulated by Zn2+ and Mg2+, but showed opposite effects. Added with Zn2+ to
      the concentration of 0.01% improves the ADH activity dramatically, but inhibits
      the activity of LDH. By contraries, added with Mg2+ improves the LDH activity
      markedly, but inhibits the ADH activity slightly. In fermentation experiment, the
      addition of Zn2+ and Mg2+ show different effects on the accumulation of ethanol,
      L-lactic acid and the biomass in mutant HBF-12. When improve the concentration of
      Zn2+, the accumulation of L-lactic acid and the biomass show the decreased trend,
      but the production of ethanol show positive effect. With the improvement of the
      concentration of Mg2+, the production of lactic acid and biomass increase
      markedly, but no effect on the production of ethanol. When ferment under the
      concentrations of Zn2+ 0.01% and Mg2+ 0.04% in fermentation medium, the lactate
      production of HBF-12 reached the highest level, 96.21 g/L.

PMID- 17037061
TI  - [The effects of the humic substances on Azoreduction by Shewanella spp].
AB  - Under anaerobic conditions, Shewanella cinicaD14(T), Shewanella baltica and
      Shewane-lla putrefaciens are capable of high-rate azoreduction and humus
      reduction. The results indicated that at low concentration ( <2 mmol/L) AQS was a
      accelerator for bacterial azoreduction. However, when the concentration of AQS
      was more than 5 mmol/L a strong inhibition was occurred. On the other hand, the
      concentration of AQDS as high as 12 mmol/L the inhibition of azoreduction was
      still not exhibited, but the effect of acceleration was gradually decreased with
      the concentration of AQDS increasing (1 mmol/L to 12 mmol/L). 6 azo dyes (Table
      1) were tested, all of which had a similar results. These results indicated that
      the humic substances were not only as a redox mediator during the azoreduction,
      but also as the competitor for electron from respiration chain. Because the humic
      substances could be act as the terminal electron acceptor for bacterial anaerobic
      respiration. AQS and AQDS exhibiting different behaviour on the azoreduction were
      determined by their standard redox potentials.

PMID- 17037062
TI  - [Diversity of actinomycetes associated with root-knot nematode and their
      potential for nematode control].
AB  - Twenty actinomycetes were isolated from root-knot nematode eggs and females
      collected from 11 plant root samples infested by Meloidogyne spp.. The isolates
      were assigned to the genera Streptomyces, Nocardia and Pseudonocardia
      respectively, based on analysis of morphological characteristics, cell-wall DAPs
      and 16S rRNA gene sequences. 80% of them were streptomycetes. Biocontrol
      potential of the isolates against Meloidogyne hapla was evaluated in liquid
      culture in vitro. The average percentages of egg parasitism, egg hatching, and
      juvenile mortality were 54.1, 40.4 and 26.2, respectively. Three Streptomyces
      strains and one Nocardia strain with high pathogenicity in vitro were selected to
      determine their ability to reduce tomato root galls in greenhouse. The results
      demonstrated good biocontrol efficacy (31.4%-56.4%) of the strains.

PMID- 17037063
TI  - [Comparative susceptibility of Myzus persicae to 16 strains of Metarhizium spp.
      from different host insects and geographic regions].
AB  - The fungal biocontrol agents Metarhizium species and varieties have been widely
      applied for insect control but their targets rarely aim at sucking-type
      homopteran insects such as aphids. To search for fungal candidates against
      aphids, 16 strains of four varieties of two Metarhizium species, most of which
      originally infected foliage insect pests in Asia, Africa and America, were
      bioassayed to compare their virulence to Myzus persicae apterae. With each
      strain, each of three conidial suspensions was sprayed onto aphids in three Petri
      dishes (about 40 aphids per dish) in a Potter Spray Tower, resulting in deposits
      of conidia for low, medium and high dosage treatments (no. conidia/mm2). After
      spray, all aphids were reared at the regime of 25 +/- 1 degree C and 12:12 L:D
      and observed daily for counts of mycosed cadavers. As a result, 10 strains of M.
      anisopliae (Ma) and M. anisopliae var. anisopliae (Maa) caused 67%-100%
      mortalities at the high dosage of about 1000 conidia/mm2 within 7 days after
      spray whereas other strains, including M. anisopliae var. majus, M. anisopliae
      var. acridum, M. flavoviride var. minus, killed a very small number of aphids
      even at the high conidial dosage. Of the 10 strains, Ma 456 and Maa 3332 were
      highly virulent to the aphid species based the modeling of their time-dose
      mortality data. The LC50 of the two strains were estimated as 113 and 260
      conidia/mm2 on day 4, 32 and 43 conidia/mm2 on day 5, 17 and 26 conidia/mm2 on
      day 6, and only 11.4 and 19.9 conidia/mm2 on day 7, respectively. Thus, both
      strains are highly potential for use in microbial control of aphids.

PMID- 17037064
TI  - [Relationships between phosphine content of samples and their microbial
      populations and enzyme activities].
AB  - The relationships between phosphine content and various microbial florae,
      activities of different enzymes were investigated. The results indicated that the
      phosphine content of samples from various environments was positively related to
      total anaerobic microorganisms, organic phosphate compounds-dissolving bacteria,
      denitrifying bacteria, alkaline phosphatase activity and dehydrogenase activity
      of the samples. The correlation coefficients (R2) for these were 0.93, 0.90,
      0.69, 0.79 and 0.82, respectively. The results also showed that the phosphine
      content was not related to total aerobic microorganisms, inorganic phosphate
      compounds-dissolving bacteria, sulfate-reducing bacteria, acidic phosphatase
      activity. In addition to formerly results, the results might infer that the
      formation of phosphine was due to the reduction of organic phosphate compounds by
      anaerobic heterotrophic microbes, especially the denitrifying bacteria by using
      reducing sugar.

PMID- 17037065
TI  - [Construction of double-labelled carbofuran-degrading bacterium Sphingomonas sp.
      CDS-1].
AB  - The genomic DNA of a carbofuran-degrading bacterium Sphingomonas sp. CDS-1 was
      digested by Sau3Al and ligated to pRobe-GFP digested by BamHI, and the product
      was transformed to the E. coli DH5alpha competent cells. Fifty positive clones
      that could emit green fluorescence under UV were selected from about 1 x 10(4)
      clones grown on selective plates AmpLB. One clone F7 with the strongest
      fluorescence was selected, the recombinant plasmid pF7 from this clone was
      digested with EcoR I & Hind III and the DNA fragment comprising gfp and promoter
      of Sphingomonas sp. CDS-1 was recovered, which was subsequently cloned into the
      broad host vector pPZP201 to construct a new plasmid pPZP201-gfp. pPZP201-gfp was
      introduced into Sphingomonas sp. strain CDS-1 by triparental conjugation to make
      strain CDS-gfp. gfp was expressed strongly and stably in strain CDS-gfp after 10
      times successive re-culturing (48 h/time). The linA gene was inserted into Not I 
      cut transposon vector pUT/mini-Tn5 to construct a new transposon vector pUT/mini
      Tn5-linA. With the aid of helper plasmid pRK600, pUT/mini-Tn5-linA was introduced
      into CDS-gfp, the dehydrochlorinase gene linA was integrated into the chromosome
      of CDS-gfp by transposing. The double labelled strain CDS-GFP-LinA was
      constructed. This strain was also a genetic engineering strain that was able to
      degrade gamma-hexachlorocyclohexane and carbofuran simultaneously. All of these
      results laid a foundation for the study of ecological performance of Sphingomonas
      sp. CDS-1.

PMID- 17037066
TI  - [Community composition and dynamics of airborne bacteria in Beijing].
AB  - Airborne bacteria are important biological components of the aerosol. They have a
      close relation with human health. The much higher concentrations can result in
      kinds of microbial disease. Using BIOLOG identification technology, the study on
      the community structure and dynamics of airborne bacteria was carried out in
      three typical functional areas in Beijing by systemic site sampling. Results show
      that the gram positive bacteria contributing 80%-85% were much more than the gram
      negative bacteria. Amongst 47 genera of bacteria including 31 Gram positive
      bacteria and 16 Gram negative bacteria, Micrococcus, Staphylococcus, Bacillus,
      Corynebacterium, and Pseudomonas were dominant, and Micrococcus contributing 20%
      30% was the most dominant genus. The concentration of airborne bacteria was
      significant lower in GGR than in CER and MTL. In a year, the bacterial
      concentrations of summer and autumn were much more than those of winter and
      spring in CER and MTL, and there were no significant variations of bacterial
      concentrations in GGR. In different periods, the lower concentration of airborne
      bacteria was exhibited at 13:00.

PMID- 17037067
TI  - [Expression of alpha-toxin gene of Clostridium perfringens type A and its primary
      immunological protective function].
AB  - Alpha-toxin gene was amplified from chromosomal DNA of Clostridium perfringens
      type A by polymerase chain reaction (PCR). PCR product was inserted into vector
      pGEM-T directly. The cloned recombinant plasmid pXCPA02 possesses positive
      nucleotide sequence of alpha-toxin. A 1.2 kb alpha-toxin gene fragment was
      cleaved with restriction endonucleases Nco I /EcoR I from plasmid pXCPA02, and
      then inserted into an expression vector pET-28c which cleaved with Nco I /EcoR I
      by blunt-end ligation. The recombinant expression plasmid pXETA02 was studied in
      detail by restriction endonucleases analysis and nucleotide sequencing. The
      results showed that the recombinant expression pXETA02 possessed a positive alpha
      toxin gene sequence and reading frame. BL21 (DE3) (pXETA02) could produce alpha
      toxin and the expressed products were recognized by alpha-toxin monoclonal
      antibodies with ELISA and Western blot. The expression optimization result
      indicated that the alpha toxin gene expression optimized condition with IPTG
      induction is culture medium pH 7.5, culture temperature 37 degrees C, joining
      IPTG to final concentration 0.8 mmol/L when the recombinant strain growth density
      OD600 achieved 0.8, and induction time 5h. The expression level of the alpha
      toxin proteins were about 34.28% of total cellular protein with IPTG induction by
      SDS-PAGE and thin-layer gel scanning analysis. The alpha toxin gene expression
      optimized condition with lactose induction is culture medium pH 7.5, culture
      temperature 37 degrees C, joining lactose to final concentration 0.1 g/L when the
      recombinant strain growth density OD600 achieved 0.8, and induction time 5h. The
      expression level of the alpha-toxin proteins were about 23.82% of total cellular
      protein with lactose induction by SDS-PAGE and thin-layer gel scanning analysis.
      More importantly, Immunization in a mouse model with crude preparation containing
      the alpha-toxin protein inclusion bodies or inactivated recombinant strain
      induced protection against at least 1 MLD of the toxin from Clostridium
      perfringens type A.

PMID- 17037068
TI  - [Comparative proteomics research on THP-1 cells infected with Brucella].
AB  - Brucella is a facultative intracellular pathogen that survives and multiplies
      inside host macrophages to cause brucellosis. The response of macrophage plays an
      essential role in the initiation of immune process following Brucella challenge.
      Nowadays, proteome approaches have been widely used in many different systems to
      investigate host-microbe interactions. The effect of pathogen-specific virulence
      mechanism can now be dissected using bacterial mutants and comparing different
      species. Attenuated vaccine strain 104M is defective in multification in host
      macrophage and is cleared relatively rapidly from tissues of the host, whereas
      virulent strains Brucella abortus 544A can produce chronic infection and cause
      brucellosis. In order to understand the underlying mechanisms of virulent
      Brucella intracellular survival, and detect the different-expressed proteins of
      THP-1 cells after infection with attenuated and virulent strains of Brucella
      abortus, a comparative proteomics research was conducted. Whole cellular protein
      profiling of THP-1 cells was presented by two dimensional (2D) electrophoresis
      and Coomassie Blue staining. After in-gel protein digestion, the different
      expressed spots were detected by matrix assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF-MS). All the peptide mass fingerprints
      (PMFs) were searched by the program Mascot developed by Matrix Science Ltd. For
      identifying proteins, database of hemo sapiens was used. A total of 38 proteins
      with changed expression level were found. These proteins can be grouped into two
      familes: (1) the expression level increased after infection with 544A; (2) the
      expression level increased after infection with 104M. Out of the 38 proteins, 10
      were mainly in the field of signal transduction, 6 were cytoskeletal proteins, 8
      were substance metabolism related proteins and 3 were cell stress and defense
      associated proteins. Functions of the remaining proteins were unknown. These
      results provide insight into the changed global protein patterns of THP-1 cells
      after infection as well as a comprehensive foundation to further study of host
      bacterial interaction.

PMID- 17037069
TI  - [Isolation and identification of Streptococcus suis serotype 2 from sick-pig
      samples of Sichuan province].
AB  - Streptococcus suis serotype 2 (SS2) is a major pathogen frequently associated
      with infections in pigs. There are presently 35 serotypes of S.suis (serotype 1
      to 34 and serotype 1/2) recognized on the basis of capsular antigens. Few people
      were reported to infect with SS2 in the past years. However, an accidental case
      happened in Sichuan province of China in 2005. Some people got ill and died, and
      all of them were closely contacted with sick pigs. Based on clinical features and
      epidemiologic data, this case could be caused by SS2 infection. Liver, spleen,
      kidney, lung and serum samples were collected and used for pathogen isolation and
      identification in laboratory, three strain bacteria were isolated. The three
      strains of SS2 showed typical morphology of SS2 on blood agar and under
      microscope with Gram stain. They were also agglutinated with standard serum of
      SS2. Biochemical characteristics of the three bacteria were tested using API 20
      strep and analyzed by API software (version 3.3), results showed they were SS2.
      Four pairs of primer were designed, which were exactly matched the extracellular
      factor gene, muraminidase released protein gene, capsular polysaccharides gene
      and 16S rRNA gene respectively. These primers were used on polymerase chain
      reaction (PCR), and the PCR products were 626bp, 885bp, 487bp and 297bp on
      agarose gel, respectively. Drug sensitivity test were also done and results
      showed that they were sensitive to cefazolin, clindamycin, erythromycin,
      levofloxacin, nitrofurantoin, penicillin-G, and vancomycin and resistive to
      tetracycline. Balb/c mice infected with the isolated SS2 strain showed swelling
      in stomach and intestine, cyanochroia at mouth and suggillation under skin, which
      were similar to the clinical features of patients. Streptococcus suis serotype 2
      were also found on lung sheeting sample under microscope with Gram stain. Rabbits
      infected with the isolated SS2 showed the similar clinical features with mice.

PMID- 17037070
TI  - [Co-expressed GP5 and M proteins of porcine reproductive and respiratory syndrome
      virus can form heterodimers].
AB  - In order to investigate the characterization of in vitro co-expressed GP5 and M
      proteins of porcine reproductive and respiratory syndrome virus (PRRSV),
      eukaryotic expression plasmids pCI-ORF5 (expressing GP5 protein alone), pCI-ORF6
      (expressing M protein alone), and pCI-ORF5/ORF6 (co-expressing GP5 and M
      proteins) were constructed. After transient transfection, Western blot analysis
      under nonreducing condition demonstrated that co-expressed GP5 and M proteins
      could form disulfide-linked heterodimers (GP5-M) in transiently transfected BHK
      21 cells. To further study the influence of GP5-M heterodimers formation on the
      subcellular localizations of GP5 or M proteins, green fluorescence protein (EGFP)
      and red fluorescence protein (RFP) were used as markers. The results of
      fluorescence distribution showed that co-expressed GP5-EGFP chimera and M-RFP
      chimera boosted the transport of GP5 from the endoplasmic reticulum (ER) to the
      Golgi complex, indicating that the formation of GP5-M heterodimers may be
      involved in posttranslational modification, transport, and subcellular
      localization of GP5. These results presented here lay foundation to further study
      the molecular mechanism of GP5-M heterodimer formation and its role in protective
      immunity of PRRSV.

PMID- 17037071
TI  - [Generation of recombinant vaccinia virus expressing attachment glycoprotein of
      Nipah virus].
AB  - The mammalian condon optimized G gene was synthesized by over-lapping PCR and
      used to generate recombinant vaccinia virus, rWR-NiV-G. The expression of Nipah
      virus G protein in rWR-NiV-G infected HeLa cells was confirmed by western-blot
      with NiV G protein specific mouse antiserum generated by DNA immunization.The
      recombinant G protein showed sensitive and specific antigenic reaction to rabbit
      serum anti-Nipah virus in indirect florescence. Syncytium formation was induced
      in BHK cells by rWR-NiV-G infection following NiV F protein expressing plasmid
      pCAGG-NiV-F transfection. Immunization with rWR-NiV-G elicited G protein specific
      antibody responses in mice. The prokaryotic expressing G protein fragment showed
      sensitive and specific antigenic reaction to NiV G protein specific antibody from
      rWR-NiV-G immunized mice serum in indirect ELISA. Furthermore, the G protein
      specific antibodies could neutralize the infectivity of the recombinant Vesicular
      Stomatitis Virus pseudotype VSVAG * F/G, in which the VSV envelope protein G gene
      was replaced with the green fluorescent protein gene (VSVAG * G, Whitt MA) and
      complemented with Nipah virus F and G glycoprotein expressed in transient (VSVAG
      * F/G).The results here demonstrated the G protein expressed by rWR-NiV-G keeps
      native immunogenicity and biological activity. The recombinant virus could be
      promising vaccine strategy for the prevention of Nipah virus.

PMID- 17037073
TI  - [Primary study on acid tolerance mechanism of a wild aciduric Rhizobium strain
      isolated from Pueraria lobata].
AB  - An aciduric Rhizobium strain, named as PR389, was isolated from the nodule of
      wild Pueraria lobata which grew in yellow soil (pH 4.6) on the Jin-yun Mountain
      in Bei-bei, Chong-qing city. The isolated strain, which could grow under pH 4.6
      distinct from the optimal pH 6.5-7.5 for rhizobium, showed some typical features
      of aciduric rhizobium. This was also confirmed by the proton flux assay. Compared
      to the acid-sensitive Rhizobium strain PR21, the cell membrane of PR389 could
      hold back excessive H entering cell. This feature can protect PR389 from harm of
      acid. In the test of acid tolerance, the aciduric ability of strain PR389 under
      low acidic (pH 3.8) was restrained by antibiotic chloramphenicol. It was
      speculated that special proteins in the cells of PR389 could be induced and
      synthesized in acidic environment.

PMID- 17037072
TI  - [Isolation, identification and phylogenetic analysis of a pathogenic bacterium in
      channel catfish].
AB  - A pathogenic bacterium (CCF00024) was isolated from the kidney and liver of the
      diseased channel catfish with acute epidemic disease. Artificial infection proved
      that the bacterium was the pathogen of the disease. Its morphological,
      physiological, biochemical characteristics and 16S rDNA sequence analysis were
      studied. The isolated strain is an aerobic, non-fermentative bacterium. The
      bacteria are gram negative, rods, with polar multi-flagella; Oxidase-negative,
      methyl-red-negative, lysine decarboxylase-positive, DNAase-positive, urease
      positive, lipase-positive and protease-positive. The bacteria can't utilize most
      of sugars with production of acid, except maltose and mannose. A phylogenetic
      tree was constructed by comparing the 16S rDNA sequence of the isolated strain
      (GenBank accession number AY970826) with other relative bacteria species in the
      RDP and GenBank databases. In the phylogenetic tree CCF00024, Stenotrophomonas
      maltophilia 13637T, Stenotrophomonas maltophilia MG958T, and Stenotrophomonas
      maltophilia M5-1 constitute a branch. The similarity value between strain
      CCF00024 and those 5 strains Stenotrophomonas maltophilia are 99.4%-99.6%.
      According to morphological, physiological, biochemical characteristics and
      phylogenetic analysis, the isolated strain (CCF00024) is identified as
      Stenotrophomonas maltophilia.

PMID- 17037074
TI  - [Construction of an engineering strain producing alkaline pectate lyase with
      pHSh].
AB  - The structure gene PL from Bacillus subtilis WSHB04-02 encoding pectate lyase was
      amplified by PCR. The pET22b(+) vector, with leader sequence PelB, harboring PL
      gene was constructed. From pET22b(+) PL, the fragment of PL and leader sequence
      PelB was amplified by PCR together, which was transformed into E. coli JMI109.
      The expression of PL in E. coli JM109 was not evidently different from E. coli
      BL21DE3 (pET22b(+) PL) which promoter is T7. SDS-PAGE analysis showed that the
      molecular weight of expressed recombinant PL was about 43 kDa which was the same
      as calculated value. The results indicated the expression of pHsh PL in E. coli
      JM109, Hsh as a promoter, was satisfied and low-cost. It is significant for large
      scale fermentation of pectate lyase.

PMID- 17037075
TI  - [Sequence analysis of integration sites of reticuloendotheliosis virus LTR in
      fowlpox vaccine virus genomes].
AB  - By use of genomic DNA prepared from 5 fowlpox virus (FPV) vaccines made in China
      (from Shandong, Beijing, Liaoning, Zhejing and Shanghai respectively) as the
      templates, reticuloendotheliosis virus (REV) LTR was amplified in PCR with a pair
      of primers synthesized according to the sequences flanking the integrated REV
      5'LTR in FPV genomes published in US and Australia. Sequence analysis indicated
      that the REV-5'LTR integration sites in genomes of all 5 Chinese PFV vaccine
      products were identical to American and Australian FPV vaccines with integrated
      REV-5' LTR. Among the 5 FPV vaccine products made in China, 3 productes Vac-B-Ch,
      Vac-D-Ch and Vac-E-Ch had the integrated REV-5' LTR sequences of 223bp with 100%
      homology to that in American vaccine Vac-3-Am and Australian vaccine Vac-M3-Au.
      The integrated 505bp REV-LTR sequences in another Chinese products Vac-A-Ch and
      Vac-C-Ch had 99.6% homology to the integrated REV-LTR of American vaccine Vac-1
      Am and Australian vaccine Vac-S-Au. However, REV-5'LTR integrated in all 5 FPV
      vaccines made in China gave only 75.4%-91.5% homology to LTR of a Chinese field
      strain HA9901 of REV. Based on the above results, it is reasonable to speculate
      that the virus stocks for the 5 Chinese FPV vaccine products were rather
      originally imported with their integrated REV LTR than recombinated with LTR of
      REV local field strains in China.

PMID- 17037076
TI  - [Arginine metabolism in wine malolactic bacteria].
AB  - Arginine metabolism in wine malolactic bacteria may increase the concentration of
      ethyl carbamate (EC, a known carcinogen with the potential toxicological effects)
      in wine, which makes a profound impact on wine hygienic quality. In fact, recent
      advanced studies have proved that arginine metabolism in wine malolactic bacteria
      is via arginine deiminase pathway (ADI pathway), and this pathway is composed of
      three enzymes: arginine deiminase (ADI), ornithine transcarbamylase (OTC),
      carbamate kinase (CK). The possible mechanisms of arginine transport and the
      regulation of major enzymes for arginine metabolism as well as the mechanism of
      ADI pathway and its molecular characteristics are reviewed. The study on arginine
      metabolism in wine malolactic bacteria has practical and theoretical significance
      for the safety and high quality of wine.

PMID- 17037077
TI  - [A novel application of baculovirus in mammalian gene therapy].
AB  - Baculovirus has been widely used for the production of recombinant proteins in
      insect cells. The extremely high yield by baculovirus-infected insect cells or
      larvae makes it an attractive tool for pharmaceutical protein production. Since
      the finding that baculovirus can efficiently transduce mammalian cells, the
      applications of baculovirus have been greatly expanded. Although AcMNPV
      (Autographa californica multiple NPV) fails to replicate in vertebrate cells, it
      does express alien genes with levels of expression that are dependent on the
      strength of the promoter used to drive transcription of the foreign gene.
      Following these findings, subsequent studies have rapidly expanded the list of
      permissive cells that include cell lines originating from human, rodent, porcine,
      bovine and even fish sources. Many tries have been done to study the mechanism of
      baxulovirus entry into mammalian cells, but the events responsible for virus
      uptake and detailed mechanisms of intracellular movement and nuclear entry of the
      virus are still largely unknown. The application of modified baculoviruses for in
      vivo gene delivery has also been demonstrated. In contrast to other commonly used
      viral vectors, baculoviruses have the unique property of being incapable of
      initiating a replication cycle and producing infectious virus in mammalian cells.
      The AcMNPV genome is large, thus rendering the virus flexibility to carry
      multiple genes or large inserts. The recombinant viruses can be readily
      constructed and produced to high titers simply by infecting insect cells,
      initiate little to none microscopically observable cytopathic effects on
      mammalian cells and have a good biosafety profile. These attributes will
      undoubtedly lead to the increased application and continued development of this
      system for efficient gene delivery into mammalian cells.

PMID- 17037078
TI  - [Progress on engineered strains for ethanol production].
AB  - With the 21 century's coming, the era of cheap oil is coming to the end. There
      has been an increasing worldwide interest in fuel ethanol. In the last two
      decades, lots of work has been done to develop strains for ethanol producing.
      Research progress on metabolic engineering of strains for fuel ethanol production
      is summarized, including genetically engineered Saccharomyces cerevisiae to
      utilize starch, pentose and cellulose, Zymomonas mobilis to ferment arabinose and
      xylose, Escherichia coli and Klebsiella oxytoca to introduce heterogenous ethanol
      production pathway. The aim of engineering these strains is to obtain an ideal
      microorganism which can converse the available carbon sources to ethanol rapidly
      and efficiently with high tolerance to ethanol and to inhibitory components in
      the cheap materials such as lignocellulose hydrolysate. The importance of fuel
      ethanol will be a stimulus to develop engineered hardy strains to utilize cheap
      materials for high ethanol concentration production. Since both Saccharomyces
      cerevisiae and Zymomonas mobilis are generally regarded as safe (GRAS),
      genetically engineered Saccharomyces cerevisiae which can utilize raw starch
      directly and recombinant Zymomonas mobilis which can ferment glucose, arabinose
      and xylose in the lignocellulose hydrolysate have potential application to
      industry in the near future.

PMID- 17037079
TI  - [Progress and investigation of neuronal plasticity interfered by Borna disease
      virus infection].
AB  - Borna disease virus (BDV) is highly neuronotropic. Recently, more and more
      investigations indicated that BDV infection was close related to human
      neuropsychic disorders. However, the mechanism underlying the disorders was
      unclear to date. Some investigators thought neuronal plasticity changes by BDV
      infection in the central nervous system may be it's cardinal basis. Many
      researchers have studied the molecular mechanisms, which might lead to
      disturbances in neuronal plasticity by BDV infection, through infection-based
      animal modes such as gerbils modes, rats modes, mice modes and transgenic mice
      modes. The results showed that neuronal plasticity was interfered by BDV
      infection through interference with trophic support from astrocytes to neurons,
      interference with amphoterin signaling and interference with neurotrophin
      signaling. The disturbances in neuronal plasticity would result in cerebral
      disorders and cause behavior alterations and psychic alterations of host. In the
      following years, the ability to manipulate the BDV genome may help uncover
      unrecognized aspects of the basic mechanisms operating in the regulation of
      neuronal plasticity of interference with neuronal physiology caused by BDV, give
      academic foundation for clinical prevention and therapy of BD.

PMID- 17037080
TI  - [Progress on lactococcus lactis expressing heterologous antigens as live mucosal
      vaccines].
AB  - Lactic acid bacteria (LAB) are natural commensals of the gastro-intestinal tracts
      of humans and most animals. They are considered to be safe bacteria with a GRAS
      (generally regarded as safe) status. The studies on LAB as live vehicles for
      expression of heterologous proteins or antigens have gained great progress in the
      past decades. Lactococcus lactis, an important species of LAB, possesses many
      properties that make it an ideal candidate for expressing and delivering
      heterologous proteins. With the significant advances in the genetic study of LAB,
      a series of constitutive or inducible gene expression systems as well as protein
      targeting systems had developed in Lactococcus lactis. Several antigens of
      pathogenic microorganisms, such as C subunit of tetanus toxin (TTFC) and the
      Brucella abortus ribosomal protein L7/L12, were successfully expressed in
      Lactococcus lactis. And it was showed that the recombinant Lactococcus lactis
      were able to induce specific mucosal immune response. It will be a great
      challenge how to make the recombinant Lactococcus lactis present heterologous
      proteins to the mucosal immune system in an effective way and induce specific
      immune response. One of the important directions for the further scientific
      development in this field is exploring protein targeting system to express
      heterologous antigens in precise locations of Lactococcus lactis. Expressing the
      antigen and cytokine simultaneously in Lactococcus lactis is an attractive
      direction as well. Using recombinant Lactococcus lactis that present antigens as
      live mucosal vaccines provides an effective way to prevent microorganisms
      invading and shows a promising future.

PMID- 17037081
TI  - The new approaches to preservation of graft cell integrity in preservation for
      transplantation.
AB  - Restoration of cell plasma membrane integrity after injury is essential for the
      survival of animal cells. In case of graft preservation or during chemotherapy in
      cancer, cell membrane integrity and the process of its repair are disrupted.
      Cytoprotective substances are important in such cases, as well as in other
      diseases, for example in myocardial infarction, acute insults and in chronic
      neurodegenerative diseases. Hyperosmolarity is a condition in which cell membrane
      stability may be damaged in vivo but preserved in the in vitro conditions.
      Hypertonicity causes water leaving from cells by osmosis, decreasing cell volume
      and increasing of intracellular ionic strength. High intracellular ionic strength
      perturbs cellular function by decreasing the rates of biochemical reaction. We
      review the new experimentally studied cytoprotective substances and their
      application in cell membrane protection. Moreover, we present our data on the
      effects of hyperosmolarity and its protective effect on cell internal structure.

PMID- 17037082
TI  - Contemporary methods for detection of microbial infections in transplanted
      tissues.
AB  - Infective processes developing after transplantation are diagnosed mainly in the
      specimens harvested from blood and exudates. Not much attention has been focused
      on identification of microorganisms present in the graft or penetrating the graft
      from the recipient. Although a progress has been made with respect to detection
      of viruses there is still little knowledge on the pathological role of bacteria,
      transplanted together with the graft or acquired from the recipient, in evoking
      or enhancing the rejection reaction (heterologous immune response). Recently
      developing molecular techniques allow us to detect bacterial genetic materials in
      clinical specimens. This article reviews commonly used methods for detection,
      identification and typing bacterial pathogens. It focuses on specific and
      universal methods based on gene sequencing, PCR and techniques based on
      polymorphic DNA. We also present the examples of genes and microorganisms
      analysed in laboratories. Together with conventional microbiological methods the
      molecular tests can serve as a key for better understanding the bacterial
      presence in tissues, not necessarily causing inflammation, quite often being
      commensal, but also evoking host reaction under certain so far not defined
      circumstances.

PMID- 17037084
TI  - Sport for the transplant athlete-just harmless fun or a valuable tool?
AB  - The persisting handicaps to full physical, mental and social rehabilitation in
      the recipient of a successful transplant are outlined. The benefit derived from
      sport with reference to the Transplant Games is summarized. An appreciation of
      the papers in this issue of the Annals of Transplantation is given. They were
      presented at the Second International Symposium on Sport and Transplantation held
      in conjunction with The European Society of Organ Transplantation on October 19th
      2005 in Geneva. The conclusion drawn is that the muscles of patients who have
      suffered end stage disease of a vital organ do not recover rapidly or
      spontaneously after a successful transplant and that the depression of VO2 Max
      gives a documented indication of this fact. The good news, however, is that
      appropriate physical activity and exercise is highly effective in overcoming the
      deficit and sport is a vital component in the rehabilitation of the transplant
      recipient.

PMID- 17037083
TI  - The response of spleen dendritic cell-enriched population to bacterial and
      allogeneic antigens.
AB  - The dendritic cells (DC) play crucial role in initiation and modulation of immune
      response especially innate immune response. We investigated the influence
      bacterial (E. coli and S. epidermidis) and allogeneic antigens (heart, skin and
      bone marrow transplants) on splenic DC- enriched population. We found that 1) the
      in culture stimulation of rat splenic DC-enriched population by E. coli,
      S.epidermidis, LPS and CpG DNA caused increase in class II-positive cells.
      Simultaneously, a decrease in percentage of EDI, B cells and OX62 migrating DC
      upon treatment with S.epidermidis was observed. LPS caused decreased frequency of
      OX62 and NK cells. 2) Similarly to the in vitro the in vivo stimulation by E.
      coli, S.epidermidis, LPS and CpG DNA increased the percentage of class II
      positive cells. There was a decrease in the ED1, OX62 and B cell populations
      following stimulation by S. epidermidis. 3) Mixed DC-enriched population and
      donor PBM culture showed high level of response in both populations. 4) Syngeneic
      and allogeneic transplants of heart, skin and BMC caused increase in class II
      positive cells. Moreover, there was an increase in frequency of the ED1 and W3/13
      populations after both syn- and allogeneic transplantation. The OX62 cells did
      not react, whereas the B cell frequency rose only after allogeneic
      transplantation. A significant decrease in NK cell population was noticed. 5) The
      in vitro and in vivo bacterial stimulation brought about expression of TLR
      receptors and Hsp. Mixed recipient DC with donor PBM culture caused expression of
      Hsp 90 but not TLRs. Allogeneic stimulation by transplanted tissues did not evoke
      expression of the investigated receptors and proteins. 6) Recipient DC-enriched
      population produced IFN gamma upon stimulation with bacteria and skin but not
      heart and BMC. Further studies on simultaneous stimulation of splenic DCs by
      bacterial and allo-antigens will throw light on additive effects of bacterial
      activation in allograft rejection.

PMID- 17037085
TI  - Exercise following organ transplantation: A critical part of the routine post
      transplant care.
AB  - There are many reasons for recommendation of regular physical activity for organ
      transplant recipients, including 1) Restoration of physical functioning following
      deconditioning experienced prior to transplant; 2) Most patients are physically
      inactivity, 3) The high prevalence of cardiovascular risk factors that may be
      modified by regular physical activity; 4) Physical activity will optimize
      physical functioning following transplant; and 5) p; hysical activity may reduce
      or attenuate side effects of immunosuppression. There are many recommendations
      for regular physical activity as an integral part of treatment of conditions that
      are common to transplant recipients, including: hypertension management;
      hyperlipidemia; Diabetes; and elevated cardiovascular disease risk. Transplant
      recipients tolerate progressive exercise training well and can achieve levels of
      functioning similar or higher than normal individuals. In order to optimize
      functioning and overall health in organ transplant recipients, regular physical
      activity should be prescribed and encouraged as a part of the routine post
      transplant care.

PMID- 17037086
TI  - Maintenance of the musculoskeletal mass by control of protein turnover: the
      concept of anabolic resistance and its relevance to the transplant recipient.
AB  - Although the overall size of the musculoskeletal mass is constrained by genetic
      limitations, both the day to day maintenance and muscle wasting and
      rehabilitation are regulated by protein synthesis (particularly the initiation
      and elongation stages of translation) and by protein breakdown. These are
      directly influenced by the nutritional state (size and composition of meals) and
      type, mode and duration of exercise. In the context of food-related changes,
      recent work has demonstrated that human muscle protein synthesis is almost
      entirely controlled by the availability of essential amino acids and protein
      breakdown by availability of insulin. Muscle protein synthesis is also markedly
      stimulated by preceding exercise in a manner independent of but additive to any
      effect of food. The sensing and signalling pathways within muscle are activated
      by food and exercise in normal healthy subjects to elevate net muscle balance for
      many hours after strenuous exercise. In many circumstances such as
      immobilisation, ageing and many chronic diseases of the lung, kidney, heart, etc
      (such as those often suffered by pre-transplant patients), the general
      debilitation includes muscle wasting. In these subjects there appears to be a
      general failure to respond adequately to food--so called "anabolic resistance".
      It seems highly likely that this circumstance will also apply to transplant
      recipients. It is also likely that anabolic resistance can be, to some extent,
      reversed by regular physical activity which may "tune up" the anabolic pathways
      to act in a more normal fashion. Nevertheless, the extent of re-growth and
      adaptation of composition of muscle in transplant patients could be hindered by
      drug treatment including the use of rapamycin (sirolimus) cyclosporine and
      corticosteroids. These predictions should be tested by examining longitudinal
      effects of different modes of exercise and nutritional regimens on rehabilitation
      of muscle in transplant patients.

PMID- 17037087
TI  - Exercising with a denervated heart after cardiac transplantation.
AB  - Heart transplantation (HTR) is now an accepted life-extending procedure for those
      dying of intractable heart failure (CHF). HTR patients expect a high quality of
      life which implies a reasonable exercise capacity. Nevertheless HTR present
      unique exercise challenges with both central and peripheral factors of limitation
      that result in peak oxygen uptakes of 60-70% of age-matched normal subjects.
      Among central factors persistent chronotropic incompetence questions the
      occurrence and role of the graft reinnervation. Among peripheral factors the
      energetic impairement of the skeletal muscle seem to result more from
      microvascular abnormalities than from an actual deficit in oxidative capacity,
      questioning the mechanism of recovery from the CHF peripheral myopathy and the
      role of immunosuppressive drugs. Endurance and resistance training programs may
      reverse at least in part most but not all of these abnormalities. Training
      permits patients to engage in sports and even to participate in competitive
      events that are rewarding to them but also to the community because it promotes
      organ donation and confidence in medical achievements. Mechanisms of exercise
      impairments and improvements resulting from training are discussed in the
      perspective of current literature. Areas of future research and recommendations
      for the practice of sports after HTR are suggested.

PMID- 17037088
TI  - The T cell and NK cell immune response to exercise.
AB  - Exercise elicits an increase in the numbers of circulating lymphocytes and
      lymphocyte subsets (including NK cells) which is followed by a decrease in the
      numbers of cells during recovery from exercise; this lymphocytopenia appears to
      be due to a decrease in the percentage of type 1 T cells and NK cells in the
      circulation at this time. A decrease in mitogen-stimulated T cell proliferation
      and T cell production of IL-2 and IFN-gamma is reported immediately after acute,
      intensive exercise. NK cell cytolytic activity per cell (NKCA) does not appear to
      change much after exercise unless the bout was prolonged, intense and stressful,
      in which case NKCA can be depressed for several hours. Resting immune function is
      not very different in athletes compared with non-athletes. However, periods of
      intensified training in already well trained athletes can result in a depression
      of immunity in the resting state which may be due to the cumulative effects of
      repeated bouts of intense exercise with the consequent elevation of stress
      hormones, particularly cortisol and anti-inflammatory cytokines (e.g. IL-6, IL
      10, IL-Ira) causing temporary inhibition of type 1 T cell cytokine production
      with a relative dampening of the type I (cell-mediated) response.

PMID- 17037089
TI  - Exercise and the brain: insight in new therapeutic modalities.
AB  - Physical exercise influences the central dopaminergic, noradrenergic and
      serotonergic systems. A number of studies have examined brain noradrenaline (NA),
      serotonin (5-hydroxytryptamine, or 5-HT) and dopamine (DA) with exercise.
      Although there are great discrepansies in experimental protocols, the results
      indicate that there is evidence in favour of changes in synthesis and metabolism
      of monoamines during exercise. The last five to ten years the microdialysis
      technique is used to explore neurotransmitter release during exercise.
      Microdialysis can collect virtually any substance from the brains of freely
      moving animals with a limited amount of tissue trauma. It allows the measurement
      of local neurotransmitter release in combination with on-going behavioral changes
      such as exercise. Microdialysis probes were implanted in different brain areas to
      monitor diverse aspects of locomotion (striatum, hippocampus, nucleus accumbens,
      frontal cortex, spinal cord), food reward (hypothalamus, hippocampus, cerebral
      cortex), thermoregulation (hypothalamus),... Although the relationship between
      physical activity and mood has long been recognized, the use of exercise training
      as a treatment for clinical depression has been the focus of rigourous study only
      recently. The available evidence provides considerable support for the value of
      exercise in reducing depressive symptoms both in healthy and clinical
      populations. Subsequently, many studies have shown that environmental stimulation
      such as 'enriched environment' and spontaneous activity elicits various plastic
      responses in the adult brain of rats. Several molecular systems such as
      neurotrophic factors, could potentially participate in the benefits of exercise
      on the brain. Several experiments indicate that voluntary wheel running in rats
      increases both cell proliferation and recruitment of new neurons in several brain
      areas. Exercise is a powerful tool to stimulate several brain processes, and it
      is becoming clear that therapeutic effects of exercise are not only good for
      cardiovascular and other diseases, but that exercise is also good for the brain.

PMID- 17037090
TI  - The limits of human athletic performance.
AB  - For each individual, there is a limit to the capacity to perform exercise. The
      limitation, however, depends on the nature of the task and is also influenced by
      a number of other factors. Muscle strength is determined largely by muscle mass,
      specifically muscle cross-sectional area, but is also influenced by neural drive
      and biomechanical factors. Endurance performance depends on both cardiovascular
      capacity and the metabolic characteristics of the skeletal muscles. These factors
      are determined in part by genetic endowment: the elite sprinter has a high
      proportion of Type 2 muscle fibres while the leg muscles of the successful
      marathon runner are composes mainly of Type 1 fibres. Whatever the genetic
      potential, expression of this depends on the intensity, duration and frequency of
      the applied training stimulus, diet and other factors. The limitation may also
      depend on environmental factors, such as altitude and temperature.

PMID- 17037091
TI  - Prope tolerance in organ grafting.

PMID- 17037092
TI  - Cadaveric organ donation following transplant games events.

PMID- 17037093
TI  - A transplant athlete's perspective.

PMID- 17037094
TI  - Pancreas after kidney (PAK) transplantation--first case in Poland.
AB  - Transplantation of pancreas is a generally accepted treatment option for patients
      with type 1 diabetes mellitus. This procedure restores physiological insulin
      secretion, resulting in long-term normoglycemia and preventing complications of
      diabetes. One of the therapeutic possibilities is pancreas after kidney
      transplantation (PAK) for patients with previous successful kidney
      transplantation. There is evidence that patient and kidney graft survival is
      higher in PAK compared with diabetic recipients of kidney or pancreas alone
      (PTA). We report a case of pancreas after kidney transplantation in a 38 year-old
      male with type 1 diabetes mellitus of 21 year duration. One year before PAK he
      received cadaveric kidney transplant. Pancreatic graft was placed on the left
      side of the pelvis and enteric drainage was used. Immunosuppression consisted of
      antithymocyte globulin (ATG), daclizumab, tacrolimus, mycophenolate mofetil, and
      steroids. Ten months after surgery the patient stays normoglycemic, insulin
      independent with good kidney function (Cr-1,5 mg/dl).

PMID- 17037096
TI  - [Is the developmental model accurate for all psychiatric disorders?].
AB  - In the 1980's a neurodevelopmental hypothesis of schizophrenia was proposed.
      Since that time, the role of early developmental age as a risk period for action
      of etiological factors in psychosis was confirmed. Additionally, many
      disturbances of pre-schizophrenic persons in the developmental age were
      demonstrated. Recently published longitudinal cohort studies indicate that
      majority of the psychiatric disorders other than schizophrenia are preceded by
      occurrence of psychiatric disorders in childhood and early adolescence. Moreover,
      in numerous studies of adult anxiety and mood disorders, the role of early risk
      factors was observed and temperament, neurophysiological and psychopathological
      disturbances in early age were reported. The resulting developmental model of
      psychiatric disorders may help in the understanding of their pathogenesis.
      Subsequently, detection and treatment of early life disturbances may
      hypothetically prevent severe psychopathological symptoms in adulthood.

PMID- 17037095
TI  - [Current problems in psychiatric health care in Poland (2005)].
AB  - The paper is a presentation of the most important and actual psychiatric health
      care problems in Poland: the financial situation of hospitals, the risk faced by
      the out-patient psychiatric care,ethical problems related to clinical practice,
      as well as issues on postgraduate education.

PMID- 17037097
TI  - [Disturbances of social cognition in schizophrenia].
AB  - Social cognition is an ability to perceive socially relevant stimuli and to
      behave accordingly. It is connected with the processing of information brought
      about by significant social stimuli. Recently, social cognition is a topic of
      intensive research in psychology, neurosciences and psychiatry. Processes
      involved in social cognition include: perception of emotion, input of eye
      contact, reaction to voice prosody or decision-making in social situations. A
      particular role is played by the mentalizing capabilities (mind-reading) i.e.
      ability to interpret behaviour of others by attributing them certain mental
      states. Such an ability is often conceptualized as the Theory of Mind (ToM). This
      paper is a review of issues connected with disturbances of social cognition in
      patients with schizophrenia. Deficits in perceptions of face emotion and
      disturbances of Theory of Mind function in schizophrenia were discussed with
      special regard to their potential role as endophenotypes of vulnerability to
      schizophrenia. Also, relations between social cognition and basic neurocognitive
      processes were presented, as well as the effect on social cognition of different
      methods of schizophrenia treatment.

PMID- 17037098
TI  - [Analysis of the seasonality of birth effect in schizophrenic patients in Poland
      with the application of the seasonal decomposition method].
AB  - INTRODUCTION: Seasonality of the birth of patients diagnosed with schizophrenia
      is one of the most repetitive phenomena in epidemiological studies on this
      illness. The paper presents a review of the literature, with an emphasis on the
      research findings and development of methods used to investigate the phenomenon.
      AIM: The aim of the study was to analyze the phenomenon of birth seasonality in
      schizophrenic patients in the Polish population, using new methods of the
      seasonal decomposition analysis. METHODS: The study utilized birth dates of
      13,668 patients diagnosed with schizophrenia according to the ICD-10 criteria,
      and discharged from all psychiatric hospitals in Poland in the years 1997-2000.
      The data on live births in the general population as published by the Main
      Statistical Office served as the reference group. 7,432,803 people were born in
      Poland in the years 1964-1976. Efforts were made to minimize the age-related
      incidence effect. In order to eliminate seasonal variations resulting from
      deviations in the number of births in the general population, an indicator of the
      number of births of patients diagnosed with schizophrenia per 10 thousand live
      births in the general population was created. A time series of 156 monthly
      observations covering the period of 13 years was produced. The data were analyzed
      using the Census II X- 11 method, one of the most recent methods to analyze time
      series and seasonal decomposition. RESULTS: The results confirm a 5-8% birth
      excess for schizophrenia in December and January.

PMID- 17037099
TI  - [Dispute over the multiple personality disorder: theoretical or practical
      dilemma?].
AB  - Dissociative identity disorder (DID) could also be referred to as multiple
      personality disorder (MPD). Due to rare occurrence and difficulty in its'
      identification it is infrequently diagnosed in Poland. The indicated disorder has
      been portrayed by the authors throughout the historical context, referring to
      initial 18th century's references concerning dissociation. A typical
      dissociatively disordered person has been characterized along with his individual
      personality categories such as: original personality, altered personality, host
      and personality fragment. Moreover various diagnosis criterions of DID have been
      introduced. DID has also been differentiated with other disorders: PTSD (post
      traumatic stress disorder) and BPD (borderline personality disorder). A
      hypothesis has been set up, stating that DID is directly correlated with the
      trauma experienced during childhood, while PTSD is linked with traumatic lived
      through events in the later period of ones' life. The most contemporary and
      frequently used research tools for DID have been indicated: dissociative
      experience scale (DES) and somatoform dissociation questionnaire (SDQ-20). Based
      upon the known literature, the authors have presented treatment methods such as
      hypnotherapy and recorded therapy sessions. It is the view of the authors that
      the switching in dissociative identity disorder is of adaptive character (it
      occurrs depending upon adaptive needs).

PMID- 17037100
TI  - [Problem-solving strategies and marital satisfaction].
AB  - AIM: This study investigated the relation between problem-solving strategies in
      the marital conflict and marital satisfaction. METHOD: Four problem-solving
      strategies (Dialogue, Loyalty, Escalation of conflict and Withdrawal) were
      measured by the Problem-Solving Strategies Inventory, in two versions: self
      report and report of partners' perceived behaviour. This measure refers to the
      concept of Rusbult, Johnson and Morrow, and meets high standards of reliability
      (alpha Cronbach from alpha = 0.78 to alpha = 0.94) and validity. Marital
      satisfaction was measured by Marriage Success Scale. The sample was composed of
      147 marital couples. RESULTS: The study revealed that satisfied couples, in
      comparison with non-satisfied couples, tend to use constructive problem-solving
      strategies (Dialogue and Loyalty). They rarely use destructive strategies like
      Escalation of conflict or Withdrawal. Dialogue is the strategy connected with
      satisfaction in a most positive manner. These might be very important guidelines
      to couples' psychotherapy. Loyalty to oneself is a significant positive predictor
      of male satisfaction is also own Loyalty. CONCLUSION: The study shows that
      constructive attitudes are the most significant predictors of marriage
      satisfaction. It is therefore worth concentrating mostly on them in the
      psychotherapeutic process instead of eliminating destructive attitudes.

PMID- 17037101
TI  - [Bright light therapy in pregnant women depression--3 case studies].
AB  - AIM: Bright light therapy (BLT) is a new method of biological treatment in
      psychiatry. Good tolerance makes it an attractive method used not only in
      seasonal affective disorder. An episode of depression during pregnancy may be a
      new indication. The study aimed to describe effects of treatment of depression in
      3 pregnant women. METHOD: The women were out-patients in their 6-th, 7-th and 8
      th months of pregnancy and diagnosed with depression according to ICD-10
      criteria. The treatment was a morning exposure to 1 hour 5 000 LUX bright light
      from Monday to Friday. The antidepressant effect was assessed after the 2nd and
      4th week of BLT. Side effects of BLT were monitored over the whole BLT treatment
      period. RESULTS: The mean improvement of depressive symptoms after 2 and 4 weeks
      of BLT was 33% and 55%, respectively. Side effects were not observed in any of
      the patients. CONCLUSIONS: Morning BLT seems to be an effective and a very well
      tolerated mode of treatment of pregnant women suffering from non-seasonal
      depression. The manner and length of BLT maintenance treatment requires further
      studies.

PMID- 17037102
TI  - [Correlation between depressive and anxiety symptoms, distress and functioning].
AB  - AIM: The aim of the study was to define the correlation between
      anxiety/depressive symptoms, distress and functioning. METHOD: The research is
      based on the analysis of 104 persons (65 women, 39 men), who were patients of
      psychiatrists (42 persons), or general physician attenders (62 persons)
      complaining of anxiety or depressive symptoms. Distress was estimated with the
      General Health Questionnaire (GHQ-30), psychopathological symptoms and diagnoses
      were evaluated with the Present State Examination (PSE) and the level of
      functioning with Global Assessment of Functioning (GAF). The intensity of ICD-10
      symptoms was calculated for: generalized anxiety disorder, agoraphobia, social
      phobia, panic disorder, depressive disorder and dysthymia. RESULTS: The lowest
      score of distress was found in the group with sub-clinical, sole anxiety or
      depressive symptoms. An intermediate level was present in the group with anxiety
      and mixed anxiety-depressive disorders, and the highest in the group with
      depression. The functioning scores were in an inverse order. CONCLUSIONS: The
      differences in scores of distress and functioning between groups of patients with
      anxiety disorders, mixed anxiety-depressive disorders and depression are
      dependent on the intensity of depressive symptoms and are independent of the
      intensity of anxiety symptoms.

PMID- 17037103
TI  - [The present application and the perspective progress of cognitive-behavioural
      therapy].
AB  - The article presents the basic principles of cognitive-behavioural therapy and
      its applications in treating depression, anxiety disorders, post-traumatic stress
      disorder (PTSD) and addictions. The possibility of using cognitive-behavioural
      interventions for chronic somatic diseases (ischaemic heart disease, skin
      diseases, insomnia, migraine and chronic prostatitis) are also suggested.

PMID- 17037104
TI  - [Sense of coherence, personality and style of coping by patients suffering from
      depressive disorders].
AB  - INTRODUCTION: At present increasing medical attention is paid to the
      salutogenesis approach suggested by Aaron Antonovsky. The main focus of interest
      in the approach is the sense of coherence. AIMS: The aim of the study was to
      define the sense of coherence and the mutual condition linked between this sense
      and some personality traits within an individual, including the styles of coping
      by men and women suffering from depression. MATERIAL AND METHODS: The research
      included the use of a SOC-29 questionnaire, NEO-FFI test and Moos' test. The
      research was conducted on 69 patients recognized to have suffered from
      depression. The patients were in treatment at The Psychiatric and Neurosis
      Disorder Clinic with Critical Intervention Ward, Medical University of Lodz.
      RESULTS: 1) A sense of coherence within an individual is considerably stronger in
      male patients. 2) Males and females differ in the realm of particular personality
      traits and the ways of dealing with every day problems. 3) Character traits and
      the ways to handle stressful situations differ among individuals in respects to
      the sense of coherence level within an individual.

PMID- 17037105
TI  - [The impact of personal resources on coping with stress in climacteric women].
AB  - Climacterium is a physiological (so absolutely normal) occurrence in a woman's
      life. Menopause is not a disease but some women have somatic and/or psychic (for
      example: stress related) problems connected with this life-stage transition. The
      presented study examined stress-coping strategies and personal coping resources
      (optimism, emotional control, sense of self-efficacy, sense of self-worth and
      sense of life satisfaction). Fifty post menopause women completed the
      psychological questionnaires. Conclusions will be presented.

PMID- 17037106
TI  - [Present and premorbid self-image in patients with coronary heart disease].
AB  - AIM: The aim of this study was to find the differences between premorbid and
      present self-image in patients with coronary heart disease. METHODS: 70 patients
      with stable coronary heart disease treated at the Internal Medicine Department of
      the Military Hospital in Lublin and 70 healthy controls were studied. Mean age of
      the investigated patients was 53.11 years. 77% of the studied patients were city
      inhabitants and 23% were countryside dwellers. Subjects were studied with the use
      of the State-Trait Anxiety Inventory, by the Adjective Check List (ACL) and a
      questionnaire designed especially for the study of sociodemographic data of the
      investigated patients. Premorbid and present self-images were compared with the
      use of the ANOVA test. RESULTS: Our results showed that there are statistically
      significant differences between premorbid and present self-image in the
      perception of patients with coronary heart disease. CONCLUSIONS: 1. In present
      self-image, compared to the premorbid one, patients with coronary heart disease
      have low self-esteem, greater fear about the future, low endurance in performing
      tasks, they are less enterprising, have lower ability to overcome stress, they
      are more dependent and have a greater need to look for safety. 2. Women with
      coronary heart disease perceive themselves as having low self-esteem, low self
      trust, more difficulties in overcoming stress and a lower ability to understand
      other people's behaviour as compared to the time before the disease. 3. Men with
      coronary heart disease perceive themselves as having less endurance, being less
      enterprising, having a negative attitude towards themselves and other people and
      being more dependant compared to the time before the illness.

PMID- 17037107
TI  - [Psychological aspects of heart transplantation].
AB  - The most important rules of heart transplantation qualification as well as the
      factors which burden patients who are treated with this method are discussed in
      the article. Particularly difficult moments for patients arethose of decision
      making regarding the transplantation, which is accompanied with fear, and
      sometimes associated with ethical or religious doubts, subsequently--the stress
      related to the time waiting for the operation, and thereafter, the rehabilitation
      demanding patient's co-operation. The difficulties associated with living with a
      transplanted heart refer to regular immunosuppressive treatment, follow-up
      visits, avoiding infections, withdrawal from drinking alcohol and smoking
      cigarettes, living in a healthy life-style. The person with a transplanted heart
      has to acquire a series of skills and perform a lot of tasks associated with
      following doctor's appropriate advises.

PMID- 17037108
TI  - [Sociodemographic factors and their influence on anxiety and depression in
      patients after limb amputation].
AB  - AIM: The aim of this study was to assess the score of HADS and the correlation
      with sociodemographic factors and personality traits in patients after limb
      amputation. METHOD: 45 patients after limb amputation due to atherosclerosis and
      30 persons from a control group participated in the study. HADS Scale and the
      Maudsley Personality Inventory created by Eysenck were used in the study.
      Socidemographic data were collected by means of the Sociodemographic data
      questionnaire. RESULTS: In comparison to the control group, patients after limb
      amputation achieved a higher score in HADS-A and HADS-D and in the N scale of the
      Maudsley Personality Inventory. Higher levels of anxiety and depression were
      noticed in patients suffering from phantom limb pain and in patients with
      neurotic personality traits. CONCLUSION: Patients after limb amputation need
      multidisciplinary care because of higher levels of anxiety and depression
      (especially patients with phantom limb pain and those with neurotic personality
      traits).

PMID- 17037109
TI  - [Personality types in patients after vertebral surgery].
AB  - AIM: To compare personality types in patients after vertebral surgery. METHOD: 74
      patients after vertebral surgery were examined with the MPI. 22 patients were
      operated because of injury. 52 patients were operated because of chronic pain
      back. The control group consisted of 20 healthy people. Maudsley Personality
      Inventory created by Eysenck, was used to study personality types. RESULTS: There
      were no differences in personality types between patients suffering from chronic
      back pain and patients operated because of injury. Statistically, a significantly
      higher score in the N scale was noticed in the group with chronic back pain in
      comparison to patients operated because of injury and in comparison to the
      control group. CONCLUSIONS: A higher score in the N scale observed in patients
      suffering from chronic back pain, may suggest a specific personality type of
      those patients. Higher level of neuroticism may create some difficulties in the
      acceptation of the illness and adaptation process. It is necessary to take
      special psychological care of those patients.

PMID- 17037110
TI  - The best methods of preventing falls in hospitals.

PMID- 17037111
TI  - Strategies for moving beyond the illness in early schizophrenia and in chronic
      kidney disease.
AB  - Although the literature suggests that loss of self is a universal concern across
      chronic illnesses in general, little consideration has been given to loss of self
      across physical and mental illnesses. The authors compare loss of self in
      individuals with a mental illness (early schizophrenia) and in those with a
      physical illness (chronic kidney disease). In this secondary analysis, focus
      group data from 2 samples are examined for similarities and differences in the
      emergent themes. While striving to be my best self getting on with life was an
      overarching goal for both groups, the strategies for achieving it differed. The
      participants engaged in activities related to approaching the illness,
      accommodating, and connecting in order to strike a balance between the demands of
      the illness and non-illness aspects of their lives. The commonalities in the wish
      to be my best self that were found in both groups indicate that the wish to
      preserve a sense of self beyond the illness may not be illness-specific. The
      preliminary results of this secondary analysis suggest that building a positive
      sense of self in the face of illness is a critical part of illness adjustment and
      that there are opportunities for nurses and researchers to learn about the
      spectrum of strategies employed by individuals as they strive to move beyond the
      illness.

PMID- 17037112
TI  - A six-month profile of community case coordinated older adults.
AB  - The purpose of this study was to assess the needs of older case coordinated
      clients receiving community health services, by examining changes in cognitive
      status, physical and mental health status, social support, risk for
      institutionalization, and service use over a 6-month period from initial intake
      into home care. Significant predictors of professional and supportive home care,
      as well as emergency room use and hospital days, were also examined. Standardized
      interviews were conducted with 234 clients at the time of referral; follow-up
      interviews were conducted with 179 of these clients after 6 months of case
      coordination. Results reveal that physical and mental health improved, while
      cognitive status remained stable. Although social interaction and instrumental
      support decreased, subjective support remained stable. Risk of
      institutionalization decreased. Occupational therapy, nursing, and homemaking
      were the most frequently used services. The best predictor of professional and
      supportive home care was a risk of institutionalization score. The needs of this
      older adult population changed even within the relatively short span of 6 months.
      Frequent review of needs in some form may be warranted in order to maintain
      effective service plans.

PMID- 17037113
TI  - Barriers to population-focused health promotion: the experience of public health
      nurses in the province of Manitoba.
AB  - There is growing evidence that population health is influenced by broad socio
      environmental factors that require population-focused health promotion
      strategies. The author reports on a study of the perspectives of public health
      nurses (PHNs) on the nature of their health promotion practice in the Canadian
      province of Manitoba, highlighting their perceptions about barriers to population
      focused health promotion. A descriptive, exploratory research design was used to
      conduct standardized open-ended interviews with 24 PHNs in 3 geographically and
      demographically diverse health authorities. There were remarkable similarities in
      PHNs' perceptions about their practice. Three categories of barrier to population
      focused health promotion were identified: barriers at the level of individual
      PHNs; organizational barriers (culture, policies, processes); and extra
      organizational barriers at the level of the community or province. The results
      point to a gap between the theory that population-focused health promotion is at
      the heart of PHN practice and the experience of PHNs at the 3 sites. A concerted
      effort to address the barriers is needed so that PHNs in Manitoba can play a
      leadership role in creating a health-care system that truly invests in population
      health.

PMID- 17037114
TI  - Incidents in a psychiatric forensic setting: association with patient and staff
      characteristics.
AB  - Patient-related incidents are of particular concern for those working with
      forensic psychiatric populations. Evidence suggests that personality, stress, and
      burnout of nursing staff are predictive of incidents. However, the exact
      relationship of these factors with staff-patient interactions and the incidents
      that occur within these interactions have not been thoroughly explored. The
      authors collected data on the nature of incidents on a forensic unit within a
      psychiatric hospital over a 1-year period, as well as data on the characteristics
      of 13 staff members. They found that 10% of patients were responsible for 58% of
      the incidents. Patients with a diagnosis of schizophrenia were disproportionately
      involved in incidents. The frequency of non-violent incidents varied among
      nursing teams to an extent greater than that expected by chance. A relationship
      between incidents and some staff characteristics was also found. These results
      highlight the need for further research into the incidents that occur in
      situations where patient attributes, nurse attributes, and environmental factors
      produce complex interactions.

PMID- 17037115
TI  - The searching, processing, and sharing of breast cancer information by women
      diagnosed with the illness.
AB  - Most women diagnosed with breast cancer seek health-related information to cope
      with the demands of the illness. However, few studies have documented how women
      actually seek, process, and share cancer-related information. This qualitative
      study explores the process of managing cancer-related information from the
      perspective of 12 women with breast cancer. Three core components of information
      management (IM) emerged from the data: initial cancer-related informational
      triggers, emotional and behavioural reactions to the information, and the IM
      outcomes of feeling relieved, hopeful, supported, or distressed. According to the
      participants, IM is an ongoing process in which the choice to continue sharing
      cancer-related information with individuals depends on women's perceptions of how
      supportive they have been.

PMID- 17037116
TI  - Field testing the WHOQOL-100 in Canada.
AB  - The purpose of this project was to test the WHOQOL-100, an instrument for
      assessing quality of life (QOL), developed to facilitate cross-cultural
      comparison. The instrument was tested with a convenience sample of 144 people.
      The mean age of participants was 58 years and 41% were female.Test-retest
      reliability was .86 for the physical domain, .78 for the psychological domain,
      .91 for independence, .87 for social relationships, .77 for environment, and .60
      for spirituality. Consistency reliability was .77 for physical, .79 for
      psychological, .89 for independence, .71 for social relationships, .80 for
      environment, and .89 for spirituality/ personal beliefs. Correlations of the
      various domains with other instruments, including the SF-36, the Self-Anchoring
      Striving Scale, and the Visual Analogue Scale for Pain, supported the convergent
      validity of the instrument. The instrument was able to discriminate between
      healthy and ill populations, providing support for construct validity.

PMID- 17037117
TI  - Self-care from the perspective of people living with diabetes.
AB  - This review presents findings from a critical integrative review of research into
      barriers to and facilitators of self-care from the perspective of people with
      diabetes. The review was motivated by a perceived need to understand self-care
      from the perspective of those living with this chronic disease and to explore the
      implications of this understanding for health-care policy in Canada. Journal
      manuscripts and dissertations exploring self-care from the perspective of adults
      with type I or type II diabetes and published in English between 1993 and 2003
      were reviewed. Both quantitative and qualitative studies were included. Studies
      were informed by varying definitions of self-care and facilitators and barriers
      emerged accordingly. An overarching thematic tension was evident, based on a view
      of self-care as revolving around the disease or evolving in the lives of people
      with diabetes. This tension has implications for health professionals and for
      those involved in policy development related to self-care.

PMID- 17037118
TI  - Canadian Academy of Health Sciences.

PMID- 17037119
TI  - Crosslinguistic perspectives on the development of prosodic words.

PMID- 17037120
TI  - Word-minimality, epenthesis and coda licensing in the early acquisition of
      English.
AB  - Many languages exhibit constraints on prosodic words, where lexical items must be
      composed of at least two moras of structure, or a binary foot. Demuth and Fee
      (1995) proposed that children demonstrate early sensitivity to word-minimality
      effects, exhibiting a period of vowel lengthening or vowel epenthesis if coda
      consonants cannot be produced. This paper evaluates this proposal by examining
      the development of word-final coda consonants in the spontaneous speech of four
      English-speaking children between the ages of one and two. Although there was no
      evidence of vowel lengthening, coda consonants were more accurately produced in
      monosyllabic target words with monomoriac vowels, suggesting earlier use of coda
      consonants in contexts where they can be prosodified as part of a bimoraic foot.
      One child also showed extensive use of vowel epenthesis and coda consonant
      aspiration concurrent with the production of codas. However, we show that this
      was due to the articulatory challenges of producing complex syllable structures
      rather than an attempt to produce well-formed minimal words. These results
      suggest that learners of English may exhibit an early awareness of moraic
      structure at the level of the syllable, but that language-specific constraints
      regarding word-minimality may be acquired later than originally thought.

PMID- 17037121
TI  - Grammar and frequency effects in the acquisition of prosodic words in European
      Portuguese.
AB  - This paper investigates the acquisition of prosodic words in European Portuguese
      (EP) through analysis of grammatical and statistical properties of the target
      language and child speech. The analysis of grammatical properties shows that
      there are solid cues to the prosodic word (PW) in EP, and the presence of early
      word-based phonology in child speech shows that EP children are aware of these
      cues. It is thus hypothesized that grammatical properties could play a role in
      the development of the PW by promoting the early production of the different word
      shapes found in the language. The analysis of statistical properties of the
      input, namely word shape frequencies in adult speech and child-directed speech,
      shows that they constrain early word shapes in child speech in ways similar to
      recent reports on other languages: a fairly high frequency of monosyllabic
      shapes, and especially of monosyllabic CV shapes, in the input agrees with the
      production of subminimal words in child speech; a fairly high frequency of
      trisyllabic and larger shapes in the input (adult speech in particular) matches
      the early development of words larger than a binary foot. These patterns,
      together with the co-occurrence of truncation to subminimal shapes in the initial
      and later stages, as well as the presence of prosodic fillers regardless of word
      size, support the claim that early words in EP are not constrained by minimality
      or maximality requirements. The potential interaction of grammar and frequency
      effects in PW acquisition is discussed in the light of the present findings and
      comparable data available in the literature for English, French, Spanish and
      Catalan.

PMID- 17037122
TI  - The acquisition of prosodic word structures in Spanish by monolingual and Spanish
      German bilingual children.
AB  - This article examines the constraints on Prosodic Word production in Spanish by
      three monolingual and three Spanish-German bilingual children from the beginning
      of word production until 2;2. It also considers the relationship between Prosodic
      Words and Phonological Phrases, and in the case of monosyllabic words, it takes
      into consideration syllable structure (i.e., presence or absence of codas), in
      order to ascertain the importance of foot binarity in early child speech.
      Although the preferred Prosodic Word shape is that of a trochee, there appear a
      few monosyllables, consisting of CVC (or CV), which are produced earlier by the
      bilinguals than by the monolinguals. The minimality constraint is violated by the
      production of CV forms. Maximality constraints are observed for a very short
      time, as unfooted syllables appear very soon, especially in the data of the
      monolinguals. However, it takes several more months until Spanish children are
      able to produce Prosodic Words containing two feet, whereas Phonological Phrases
      constituted by two disyllabic Prosodic Words are produced earlier by some
      children. It is proposed that such data can be optimally treated by means of
      constraints, and their relevance to the question of whether prosodic structure is
      acquired bottom-up is briefly discussed.

PMID- 17037123
TI  - The relevance of metrical information in early prosodic word acquisition: a
      comparison of Catalan and Spanish.
AB  - This paper focuses on the development of Prosodic Word shapes in Catalan, a
      language which differs from both Spanish and English in the distribution of PW
      structures. Of particular interest are the truncations of initial unstressed
      syllables, and how these develop over time. Developmental qualitative and
      quantitative data from seven Catalan-speaking children reveal that maximality
      constraints are active at two stages, namely, the moraic trochee stage, and the
      bisyllabic foot stage. One of the noteworthy differences between Catalan and
      Spanish is the rate of acquisition of weak initial syllables in WS words, as
      Catalan learners omit initial syllables in WS target iambs for a significantly
      longer time than Spanish learners, despite the fact that Catalan is a language
      where the bisyllabic iambic WS pattern is more frequent than in Spanish. We claim
      that this asymmetry in the course of development of PWs can be attributed to the
      frequency of exposure to different metrical models. In Catalan (and also in
      English), the high frequency of CVC structures boosts the availability of the
      moraic trochee in initial stages. Thus the data provide crucial evidence that
      children at early stages of PW production are especially sensitive to the
      frequency distribution of foot structure in the input. In general, the behavior
      of Catalan PW acquisition significantly supports the idea that the course of PW
      development is strongly influenced by language-specific distributions of prosodic
      structures (especially feet) in the target language (see Demuth, 1996a, 2001a,
      2003; Lleo, 2002; Prieto, Bosch-Baliarda, and Saceda-Ulloa, 2005; and Zamuner,
      Gerken, and Hammond, 2004, among others).

PMID- 17037124
TI  - Input frequency and word truncation in child Japanese: structural and lexical
      effects.
AB  - Recent research indicates that the statistical properties of the input have an
      impact on the prosodic shape of young children's word production. However, it is
      still not clear whether the effects of input statistics emerge from the frequency
      of prosodic structures or the frequency of individual lexical items. This issue
      is investigated in this study by analyzing cases of word truncation spontaneously
      produced by three Japanese-speaking children (1;5-2;1) and the frequencies of
      relevant words and prosodic word structures produced by their mothers. A
      significant correlation was found between children's truncation rates for
      individual target words and the frequency of the same words in the maternal
      input, but not between the truncation rates for different prosodic word
      structures and the frequencies of the corresponding structures in maternal
      speech. The size and shape of truncated outputs were better explained in terms of
      their correspondence to the target structures than the frequencies of shorter
      forms in the input. The results indicate that variation in early word truncation
      is systematically related at least to the lexical frequency of the target words,
      and that input frequency has a clearer connection to what truncates than how it
      truncates.

PMID- 17037125
TI  - Characterisation of the biosand filter for E. coli reductions from household
      drinking water under controlled laboratory and field use conditions.
AB  - More than a billion people in the developing world lack access to safe and
      reliable sources of drinking water. Point of use (POU) household water treatment
      technology allows people to improve the quality of their water by treating it in
      the home. One emerging POU technology is the biosand filter (BSF), a household
      scale, intermittently operated slow sand filter. Laboratory and field studies
      examined Escherichia coli reductions achieved by the BSF. During two laboratory
      studies, mean E. coli reductions were 94% and they improved over the period of
      filter use, reaching a maximum of 99%. Field analysis conducted on 55 household
      filters near Bonao, Dominican Republic averaged E. coli reductions of 93%. E.
      coli reductions by the BSF in laboratory and field studies were less than those
      typically observed for traditional slow sand filters (SSFs), although as for SSFs
      microbial reductions improved over the period of filter use. Further study is
      needed to determine the factors contributing to microbial reductions in BSFs and
      why reductions are lower than those of conventional SSFs.

PMID- 17037126
TI  - Does improved access to water supply by rural households enhance the concept of
      safe water at the point of use? A case study from deep rural South Africa.
AB  - The concept of safe water is defined by three principles: the health-related
      quality must be suitable, the supply/source must be accessible and the water must
      constantly be available in quantities sufficient for the intended use. If any one
      (or more) of these three elements is missing from a water services improvement
      programme, providing safe water is not successfully achieved. A study in a deep
      rural area in South Africa showed that providing small communities, using
      untreated river water as their only water source, with good quality water through
      a piped distribution system and accessible at communal taps did not fall within
      our parameters of safe water. The parameters for measuring the three principles
      were: absence of Escherichia coli in drinking water samples; accessibility by
      improving tap distances to within 200 m from each household; availability by
      assessing whether households have at least 25 L per person per day. Results show
      that although E. coli levels were reduced significantly, households were still
      consuming water with E. coli numbers at non-compliant levels. Access (distance)
      was improved from an average of 750 m from households to river source to an
      average of 120 m to new on-tap source points. This did not result in significant
      increases in household quantities, which on average remained around 18 L per
      person per day.

PMID- 17037127
TI  - Predictive input parameters for enteric virus presence at the inlet of a potable
      water supply.
AB  - Kentucky river water samples were collected at the input of a potable water
      supply weekly, for a period of two years. Eighteen parameters were analysed
      and/or recorded for each weekly observation. The variables were of a physical,
      chemical and biological nature. Enteric virus presence was detected by cell
      culture analysis from approximately 200 L samples of river water. A database of
      108 observations was assembled. Of these only 100 complete observations were used
      for the modelling analysis. Model input parameters were selected solely based on
      their statistical significance in forward, backward and stepwise selection
      procedures. Multivariate logistic regression (MLR) was used to determine the
      relative significance of the input parameters for predicting the presence or
      absence of enteric virus. The final, best-fit MLR model that used log-transformed
      values for enterococci, the AC/TC ratio, faecal coliforms (FC) and temperature
      demonstrated 82.5 and 81.4% sensitivity and specificity, respectively.

PMID- 17037128
TI  - Removal of cyanobacteria, cyanotoxins, heterotrophic bacteria and endotoxins at
      an operating surface water treatment plant.
AB  - The removal of cyanobacteria, hepatotoxins produced by them (microcystins),
      phytoplankton, heterotrophic bacteria and endotoxins were monitored at a surface
      water treatment plant with coagulation, clarification, sand filtration,
      ozonation, slow sand filtration and chlorination as the treatment process.
      Coagulation-sand filtration reduced microcystins by 1.2-2.4, and endotoxins by
      0.72-2.01 log10 units. Ozonation effectively removed the residual microcystins.
      The treatment process reduced phytoplankton biomass by 2.2-4.6 and heterotrophic
      bacteria by 2.0-5.0 log10 units. In treated water, the concentration of
      microcystins never exceeded the WHO guide value (1 microg/L), but picoplankton
      and monad cells were often detected in high numbers. The heterotrophic bacterial
      isolates from the treated waters belonged to genera Sphingomonas, Pseudomonas,
      Bacillus, Herbaspirillum and Bosea.

PMID- 17037129
TI  - Accumulation of copper and silver onto cell body and its effect on the
      inactivation of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa, a gram-negative rod bacterium, is a causative agent of
      waterborne pneumonia and presents high tolerance against conventional
      disinfectants. The inorganic biocidal reagents, copper and silver, were applied
      to inactivate P. aeruginosa inoculated in a synthetic drinking water (SDW).
      Additionally, the relationship of the specific amount of accumulated copper and
      silver reagents (Cs) on P. aeruginosa with inactivation profile was elucidated in
      this study. Flow cytometry (FCM) following staining with SYTO 9 and PI was used
      for detection of bacterial viability and density. Individual copper and silver
      reagents, and their combination, exhibited excellent biocidal abilities even at
      the concentration of 0.05 mgCu/L and 0.005 mgAg/L. The critical amounts of
      accumulated disinfectant (Cs) were calculated at 2.82 x 10(-7) microgCu/cells and
      5.13 x 10(-8) microgAg/cells; at an incubation of 70 h. Consequently, the role of
      disinfectant on the inactivation of P. aeruginosa and the assessment of biocidal
      ability of copper, silver, and their combination were successfully explained by
      evaluating the terms Cs and Cc.

PMID- 17037130
TI  - Combined use of microbiological and non-microbiological data to assess treatment
      efficacy.
AB  - The treatment efficacy for reducing Campylobacter concentrations by a drinking
      water treatment plant was assessed using a stochastic Monte Carlo model. The goal
      of the study was to reduce uncertainty of the results by combining
      microbiological and non-microbiological data in an advanced treatment assessment.
      Combining raw water Campylobacter and E. coli data reduced the uncertainty on raw
      water (peak) concentrations five-fold. Similar improvement was achieved for rapid
      sand filtration. Ozone disinfection was modelled based on ozone concentrations,
      contact time and temperature. Since this data was available, whereas most
      microbiological analyses at this point were negative, uncertainty was reduced
      three-fold. The slow sand filtration assessment could not be improved; however,
      since previous steps contained less uncertainty, this did not increase
      uncertainty by much. The study showed that using appropriate data for each
      treatment step can greatly reduce uncertainty in treatment assessment.

PMID- 17037131
TI  - Coliforms and other microbial indicators occurrence in water and biofilm in full
      scale distribution systems.
AB  - Biofilm and microbial water quality were studied in four middle size full-scale
      distribution systems (DS) in France serving 5,000-30,000 inhabitants (maximum
      residence time 23-160h) through three sampling campaigns over 1 year. Three of
      these DSs were chosen because of a quite high occurrence of bacterial indicators
      (i.e. total coliforms), the last DS was considered as a reference. Biofilm was
      studied on cast iron coupons incubated for more than 1 month in devices
      continuously fed with water from the DS in conditions imitating those met in DS.
      The devices were located at different points (4-6) along each DS. The abundance
      of bacteria in biofilm was estimated by heterotrophic plate counts (HPC) after
      detachment of the biofilm from the support by sonication. Microbiological water
      quality was estimated in parallel; analysis of total coliforms, E. coli,
      enterococci and anaerobic sulphide-reducing bacteria spores (ASRB spores) was
      carried out in biofilm and water. Over the period of the study, 171 water samples
      and 57 biofilm samples were collected. Over these 171 waters, 19 (11%) were
      positive for at least one of the measured indicators while two biofilm samples
      were positive (3.5%). Significant differences were observed in the levels of
      contamination between the DSs. High residence time in the DS, low disinfectant
      residual and high temperature increased the risk of indicator occurrence in the
      water phase. Due to the low number of biofilm samples positive for bacterial
      indicators, the data collected in the present study did not allow observation of
      a direct association between biofilm and water contaminations, even if the
      occurrence of indicators in water appeared on DSs with the highest density of
      biofilm (HPC).

PMID- 17037132
TI  - Effect of temperature and pipe material on biofilm formation and survival of
      Escherichia coil in used drinking water pipes: a laboratory-based study.
AB  - Segments of used drinking water pipes of galvanised steel (GS), cross-linked
      polyethylene (PEX), copper pipes (Cu) or new medium-density polyethylene (PE)
      were investigated for the formation of biofilm and survival of E. coli in biofilm
      and in the water phase. Pipes were filled with water and incubated at 15 degrees
      C or 35 degrees C under static conditions. Biofilm formation was followed during
      32, 40 and 56 (58) d. The most dense biofilm was formed on GS, reaching
      approximately 4.7 x 10(5) CFU/cm2 measured as heterotrophic plate count (HPC),
      and at the other materials the density reached 3 x 10(3) CFU/cm2 on PE and PEX
      and 5 x 10(1) and 5 x 10(2) CFU/cm2 on Cu pipes after 58d at 15 degrees C.
      Biofilm HPC values were higher at 35 degrees C than at 15 degrees C, with only
      slightly higher values on the metals, but 100-fold higher on PE and PEX.
      Adenosine triphosphate (ATP) measurements confirmed the general trends observed
      by HPC. Higher temperature was seen to be an important factor reducing E. coli
      survival in the water phase in drinking water pipes. At 15 degrees C E. coli
      survived more than 4 d in GS and Cu pipes and 8 d in PE pipes, but was not
      detected after 48 h at 35 degrees C. The E. coli survived longer at both
      temperatures in the glass control bottles than in the drinking water pipes.
      Despite the obvious biofilm formation, E. coli was not detected in the biofilm at
      any of the investigated surfaces.

PMID- 17037133
TI  - Survival of Campylobacter jejuni in potable water biofilms: a comparative study
      with different detection methods.
AB  - Campylobacteria are important foodborne pathogens. C. jejuni bacteria have caused
      several drinking water-related epidemics in Finland. Normally, C. jejuni is not
      able to multiply in drinking water or in biofilms although it may survive in
      biofilms. The survival of C. jejuni in biofilms was studied using the Propella
      biofilm reactor. The number of bacteria was analysed with traditional culture
      methods and with fluorescence in situ hybridisation (FISH). By culture methods C.
      jejuni was detectable for only 1 d after spiking whereas bacteria were found from
      biofilms for at least 1 week after spiking and from outlet water of the reactor
      for 3 weeks when using FISH. These results suggested that C. jejuni may survive
      in biofilms and culture methods probably seriously underestimate the real number
      in water and in biofilms.

PMID- 17037134
TI  - Modelling the length of microbiological protection zones around phreatic sandy
      aquifers in The Netherlands.
AB  - The aim of the current study was to calculate the size of protection zones around
      (sub)oxic and anoxic sandy aquifers without confining layers using a virus
      infection and transport model. The maximum allowable virus infection risk was 10(
      4)/person/year at the 95% confidence level. Model results demonstrated that
      phreatic (sub)oxic sandy aquifers in The Netherlands required protection areas
      with a residence time of 43-117 d to ensure that the maximum virus infection risk
      would not be exceeded. This was 0.7-2 x the current guideline of 60d. In
      contrast, phreatic anoxic sandy aquifers without confining layers needed
      protection zones of 555-898d to stay below the maximum virus infection risk, 9.5
      15 x the current guideline. A sensitivity analysis of the model demonstrated that
      the calculated protection zone was most sensitive for virus inactivation rate and
      collision efficiency. Values of both parameters were predicted from values
      obtained from previously published field and laboratory studies. At present, as
      it is unknown if these values can also be used at other locations, model results
      should be interpreted with care.

PMID- 17037135
TI  - Using a weight-of-evidence approach for management of watersheds.
AB  - This research used a weight-of-evidence approach to evaluate sources of
      contaminants in a drinking water watershed that serves as part of the City of
      Boston's water supply. The approach incorporated land use analysis using GIS,
      sanitary surveys, traditional water quality monitoring and microbial source
      tracking (MST) tools. Case-study tributaries were selected based on elevated
      faecal coliform counts. Land use analysis and sanitary surveys were used to
      identify suspected microbial sources, including residential septic systems,
      agricultural animal operations, commercial/industrial operations and wildlife
      activity. Sampling sites were selected to hydrologically isolate potential
      contamination sources. Samples were collected seasonally over 1 year and analysed
      for traditional and MST parameters. Results demonstrated that both septic systems
      and a horse stable were contributing microbial loads in the first tributary. In
      the second tributary, septic systems from the townhouses were contributing
      microbial loads while a plant nursery was contributing organic matter. This
      evidence was used to evaluate best management practices to mitigate the
      contamination.

PMID- 17037136
TI  - Membrane separation of indigenous noroviruses from sewage sludge and treated
      wastewater.
AB  - In this study, feasibility of membrane separation for the removal of indigenous
      noroviruses (NVs) is evaluated. The indigenous NV gene was never detected from
      ultrafiltration (UF) permeates of sewage sludge and treated wastewater.
      Indigenous NV gene was also not detected from permeates of sewage sludge and
      treated wastewater by microfiltration (MF) with a pore size of 0.1 microm
      (MF0.1). Even though the pore size of MF (0.1 microm) was much larger than the
      diameter of virus particle (approximately 30-40nm), more than 4-log10 reduction
      value (LRV) at maximum was achieved by membrane separation with MF0.1. NV genes
      were often detected from permeates of sewage sludge and treated wastewater by MF
      with a pore size of 0.45 microm (MF0.45), although the maximum log10 reduction
      values were more than 3.59 for sewage sludge and more than 2.90 for treated
      wastewater. It is important to verify factors determining the removal efficiency
      of viruses with MF membranes.

PMID- 17037137
TI  - UV disinfection of wastewater effluents for unrestricted irrigation.
AB  - Wastewater reuse in arid regions is important for the production of a water
      resource to be utilised for non-potable purposes and to prevent the environmental
      transmission of disease-causing agents. This study was conducted to evaluate the
      effect of water quality on the comparative disinfection efficiency of viruses,
      bacteria and spores by UV irradiation. Furthermore, the microbial quality of
      effluent produced by coagulation, high rate filtration (HRF) and either UV
      irradiation or chlorination was determined. Using low pressure collimated beam, a
      UV dose of 80 mWs/cm2 was needed to achieve a 3-log10 inactivation of either
      rotavirus SA-11 or coliphage MS2, whereas over 5-log10 inactivation of E. coli
      was reached with a dose of only 20 mWs/cm2. B. subtilis inactivation was found to
      be linear up to a dose of 40 mWs/cm2 and then a tailing up to a UV dose of 120
      mWs/cm2 was observed. It is worth noting that effluent turbidity of < 5 NTU did
      not influence the inactivation efficiency of UV irradiation. Operation of a pilot
      plant to treat secondary effluent by coagulation, HRF and UV disinfection at a UV
      dose of 80 mWs/cm2 resulted in the production of high quality effluent in
      compliance with the Israel standards for unrestricted irrigation (< 10 CFU/100 mL
      faecal coliform and turbidity of < 5 NTU). Sulphite reducing clostridia (SRC)
      were found to be more resistant than coliphages and F coliform for UV
      irradiation. The results of this study indicated that UV disinfection is suitable
      for the production of effluents for unrestricted irrigation of food crops.

PMID- 17037138
TI  - Evaluation of activated sludge treatment and the efficiency of the disinfection
      of Giardia species cysts and Cryptosporidium oocysts by UV at a sludge treatment
      plant in Campinas, south-east Brazil.
AB  - Among many waterborne diseases the giardiasis and cryptosporidiosis are of
      particular public health interest, because Giardia cysts and Cryptosporidium
      oocysts can persist for long periods in the environment, and both pathogenic
      protozoa have been implicated as the cause of many outbreaks of gastroenteritis
      in the last 25 years. In order to evaluate the efficiency of cysts and oocysts'
      removal by the activated sludge process, and by UV reactor in inactivating cysts
      and oocysts in one wastewater treatment plant (WWTP) of Campinas, three sampling
      points were selected for study: (1) influent, (2) treated effluent without UV
      disinfection and (3) treated effluent with UV disinfection. Giardia spp. cysts
      prevailed with higher density in the three different sample types.
      Cryptosporidium spp. oocysts were observed in only two samples of influent and
      just one sample of treated sewage with UV disinfection. In the animal infectivity
      assay for Giardia spp, one mouse of the UV treated group revealed trophozoites in
      intestinal scrapings. The results of the present study indicate that treatment by
      activated sludge process delivered a reduction of 98.9% of cysts and 99.7% of
      oocysts and UV disinfection was not completely efficient regarding the
      inactivation of Giardia cysts in the case of the WWTP studied.

PMID- 17037139
TI  - Impact of sewage treatment plants and combined sewer overflow basins on the
      microbiological quality of surface water.
AB  - In a small river catchment, microbiological quality of different sewage treatment
      plants under regular conditions and in case of heavy rainfall, when combined
      sewage overflow basins (CSOs) are activated, was examined regarding microbial
      indicators and pathogens. In the watercourse, no self-cleaning effects could be
      observed. Small compact treatment plants discharge treated wastewater with a poor
      microbiological quality compared to river water quality and the quality of
      treated wastewater of larger plants. During storm water events, concentrations of
      microorganisms downstream of sewer overflows were approximately two logs higher
      than during dry weather conditions. Concentrations of parasites decreased slowly
      during the overflow, in parallel to filterable matter and particle-bound
      substances. The annual load of microorganisms originating from CSOs significantly
      exceeds the load from treated effluent of the sewage plants. Thus, an improved
      hygienic quality of the water course could be achieved by preventing overflows
      and by enhancing sewage treatment plants.

PMID- 17037140
TI  - Bacteroides spp. as reliable marker of sewage contamination in Hawaii's
      environmental waters using molecular techniques.
AB  - Standard PCR (SPCR) and quantitative PCR (QPCR) assays using primers for general
      and for human-specific Bacteroides 16S rRNA markers were selected as the
      molecular tests to assess sewage contamination in recreational waters of Hawaii
      and these same water samples were assayed for culturable concentrations of
      selected faecal microbial indicators. The results of this study showed that the
      general primer for Bacteroides was not useful because ambient and polluted water
      samples were positive for this marker. However, use of human-specific primers
      reliably detected sewage contamination. The human-specific Bacteroides detection
      data supported previously reported conclusions that concentrations of alternative
      faecal indicators (C. perfringens, FRNA coliphages) but not traditional faecal
      indicators (faecal coliform, E. coli, enterococci) are reliable indicators of
      faecal contamination in Hawaii's environmental waters. The QPCR assay for the
      human-specific Bacteroides 16S rRNA marker was faster, more sensitive and more
      reliable than comparable SPCR assay because OPCR assay provided additional
      information such as melting temperatures, which confirmed that the right
      amplicons were being measured and Ct values, which indicated the relative level
      of faecal contamination.

PMID- 17037141
TI  - Microbiological quality of reclaimed water used for golf courses' irrigation.
AB  - Microbial quality of reclaimed water used for irrigation in two golf courses
      located in the southern Iberian Peninsula (Spain and Portugal) was evaluated.
      Bacterial indicators for faecal pollution (total and faecal coliforms,
      Escherichia coli and enterococci) were tested by membrane filtration using
      appropriate selective media. In addition, somatic E. coli bacteriophages, enteric
      viruses (entero-, hepatitis A and rota-) and Legionella pneumophila were also
      analysed. The results obtained showed that all wastewater treatment processes
      reduced adequately the number of indicator microorganisms although a significant
      correlation between pathogenic and indicator microorganisms tested was not found.
      L. pneumophila was detected by PCR but not confirmed by culture. Survival
      experiments of pathogenic microorganisms in aerosols and irrigated turf are
      conducted to determine the health hazards for the golf practice and to propose a
      microbial standard for wastewater used for irrigation of golf courses.

PMID- 17037142
TI  - Quantification and genotyping of Cryptosporidium spp. in river water by quenching
      probe PCR and denaturing gradient gel electrophoresis.
AB  - A new detection method was developed for the simultaneous quantification and
      genotyping of Cryptosporidium spp. in river water. Several modifications made to
      the US EPA Method 1623 enabled high and stable recovery of Cryptosporidium from
      40 L of river water (geometric mean = 35%, standard deviation = 8.7%). Quenching
      probe PCR (QProbe PCR) was used to quantify the 18S rRNA gene of Cryptosporidium
      spp. This method could successfully detect single oocysts in a sample, and the
      lower quantitation limit was as low as 2.5 oocysts/sample. In addition,
      denaturing gradient gel electrophoresis (DGGE) followed by DNA sequencing was
      used to identify the genotypes. These methods were applied to detect
      Cryptosporidium spp. in the Koyama River, Japan. The positive ratio was 69%
      (11/16) with the maximum concentration of 59 oocysts/100 L. Seven genotypes
      including two novel ones were identified. These results showed that this
      detection method could provide valuable information on Cryptosporidium in river
      water, both in the concentration and in the genotypes, which is essential for the
      precise assessment of waterborne risk to human health.

PMID- 17037143
TI  - Analysis of enterococci using portable testing equipment for developing countries
      -variance of Azide NutriDisk medium under variable time and temperature.
AB  - This report compares the enterococci count on samples obtained with Azide
      NutriDisk (AND) (sterile, dehydrated culture medium) and Slanetz and Bartley (SB)
      medium when exposed to a variable in incubation time and temperature. Three
      experiments were performed to examine the recovery of enterococci on AND and SB
      media using membrane filtration with respect to: (a) incubation time; (b)
      incubation temperature; and (c) a combination of the two. Presumptive counts were
      observed at 37, 41, 46 and 47 degrees C and at 20, 24, 28 and 48 h. These were
      compared to AWWA standard method 9230 C (44 degrees C, 44 h). Samples were
      confirmed using Kanamycin Aesculin Azide (KAA) agar. Friedman's ANOVA and
      Students t-test analysis indicated higher enumeration of enterococci when grown
      on AND (p = 0.45) than SB (p = < 0.001) at all temperatures with a survival
      threshold at 47 degrees C. Significant results for AND medium were noted at 20 h
      (p = 0.021), 24 h (p = 0.278) and 28 h (p = 0.543). The study concluded that the
      accuracy of the AND medium at a greater time and temperature range provided
      flexibility in incubator technology making it an appropriate alternative to SB
      medium for monitoring drinking water using field testing kits in developing
      countries.

PMID- 17037144
TI  - Direct detection of bacterial faecal indicators in water samples using PCR.
AB  - The presence of enteric pathogens in water resources represents a serious risk
      for public health. Therefore, their precise detection, and especially detection
      of E. coli, which is obviously regarded as the main indicator of faecal
      contamination of water, is an essential step in ensuring bacterial safety of
      water. Numerous PCR protocols for detection of E. coli have been published to
      date. They are usually based on amplification of regions derived from lacZ (beta
      D-galactosidase) and uidA (beta-D-glucuronidase) gene sequences. However, these
      methods are not universal enough for precise detection of all E. coli strains
      found in water samples. We developed a novel triplex PCR method for detection of
      E. coli in which cyd gene coding for cytochrome bd complex was co-amplified along
      with lacZ and uidA genes. Our triplex PCR approach significantly increases the
      specificity and reliability of E. coli detection in water samples. This approach
      allowed us to distinguish Shigella flexneri from E. coli. In addition, we were
      able to detect even non-coliform Klebsiella and Raoutella spp., some of which can
      also cause infections to humans.

PMID- 17037145
TI  - Comparison of three different media for the detection of E. coli and coliforms in
      water.
AB  - The European Drinking Water Directive defines reference methods for the
      enumeration of microbiological parameters in drinking water. The method to be
      used for Escherichia coli and coliforms is the membrane filtration technique on
      Lactose TTC agar with Tergitol 7. Many technical drawbacks of the procedure, as
      well as its limitations regarding the recent taxonomy of coliforms, make it
      necessary to evaluate alternative methods. Two alternative assays, a chromogenic
      media (m-ColiBlu24) and a defined substrate technology-DST test (Colilert
      18/Quanty Tray) were compared with the ISO standard with attention to the
      phenotypic characteristic of the isolates. Results showed that the ISO method
      failed to detect an important percentage of coliforms and E. coli while m
      ColiBlu24 and Colilert 18 provided results in a shorter time allowing the
      simultaneous detection of E. coli and coliforms with no further confirmation
      steps.

PMID- 17037147
TI  - The association of E. coli and soil particles in overland flow.
AB  - The removal of E. coli from overland flow under saturation-excess runoff
      conditions was investigated in experimental field plots that were 1 m wide and 5
      m long. Variation in the attenuation of bacteria and distance transported was
      quantified under contrasting flow conditions. In addition, the impact of soil
      tillage upon microbial attenuation was examined by comparing results derived from
      grassed plots (intact) with those subject to tillage with the soil left bare
      (cultivated). For intact plots subjected to a flow of 2 L/min, 27% of the E. coli
      in the flow was removed after 5 m with removal following a logarithmic function
      with respect to distance. For the higher flow rates of 6 L/min and 20 L/min, no
      attenuation trend was observed over this distance. E. coli removal during flow
      across the cultivated plots was significantly greater compared to the intact
      plots. This was attributed to a greater infiltration rate in the cultivated plots
      (due to the tillage) which promoted a greater volume of flow to pass through the
      soil matrix, providing the opportunity for filtration and adsorption of microbes.
      Logarithmic trends with respect to distance were observed for all flow rates
      tested on the cultivated plots (2, 6 and 20 L/min). Total removal after 5 m at a
      flow rate of 2 L/min was 41% and again removal efficiency decreased as the flow
      rate increased. Analysis of the transported state of the E. coli revealed that
      the bacteria were being transported predominantly in particles less than 20
      microm in diameter and were not attached to large (dense) soil particles. The
      limited removal (< 50%) of bacteria from overland flow under saturation-excess
      runoff conditions in these experiments appeared, therefore, to be primarily due
      to a lack of settling or deposition. Instead, most bacteria remained entrained
      within the overland flow down the length of the plots.

PMID- 17037146
TI  - Culture of Helicobacter pylori from domestic water samples--the impact of strain
      variation on growth on solid and in liquid media.
AB  - Helicobacter pylori is an important global human pathogen and there is growing
      evidence from PCR assays that contaminated drinking water might be a possible
      source of infection in some circumstances. There are no validated protocols for
      direct isolation but various culture media have been developed for possible
      environmental sampling. Our aim here was to investigate how inter-strain
      variation might affect the interpretation of results with such media. Two
      laboratory adapted reference strains and four recent clinical isolates were
      tested on four solid media and in ten liquid media. Considerable variation was
      found between strains in their ability to recover on the different media after
      stress exposure (suspension in sterile tap water). Generally, clinical isolates
      were less robust than the laboratory-adapted strains and, overall, the former
      required longer recovery times. Our findings highlighted the importance of using
      a range of isolates for evaluations, as examination of laboratory-adapted strains
      alone did not provide an accurate representation of the utility of media that may
      be used to recover H. pylori from water.

PMID- 17037148
TI  - Adsorption of viruses to soil: impact of anaerobic treatment.
AB  - The adsorption of viruses in untreated flushed dairy manure wastewater (FDMW),
      anaerobically digested flushed dairy manure wastewater (ADFDMW) and groundwater
      to sandy soil was investigated. Batch adsorption studies showed differential
      adsorption of viruses in groundwater to soil. Less than 75% of PRD1 and MS2 added
      to groundwater adsorbed after 1 h, but greater than 95% of phiX174 and poliovirus
      1 adsorbed to the soil. Adsorption differences in groundwater were related to the
      isoelectric points of the viruses. Suspending phages in untreated and treated
      wastewater reduced adsorption compared with groundwater. For MS2, more phages
      were adsorbed using ADFDMW than with FDMW. Adsorption of poliovirus 1 was not
      affected by FDMW and ADFDMW. Small column studies (6 x 2.5 cm) produced a similar
      trend in that adsorption was observed with groundwater and both FDMW and ADFDMW
      reduced virus adsorption. Groundwater, FDMW or ADFDMW did not affect the
      adsorption of poliovirus 1 in column studies. The major difference between FDMW
      and ADFDMW was in mobilisation of adsorbed viruses. The application of FDMW to
      soil columns with adsorbed viruses caused significantly more viruses to be
      mobilised than did the application of rainwater or ADFDMW. These results showed
      that treating FDMW by anaerobic digestion increased the adsorption of viruses to
      soil and decreased detachment of adsorbed viruses. As the potential for new
      zoonotic pathogens becomes known, the treatment of animal wastes may become
      mandatory. The assessment and management of viruses in manure for addressing
      possible risk to animal and human health is of interest.

PMID- 17037149
TI  - Comparative stability and growth requirements of S. aureus and faecal indicator
      bacteria in seawater.
AB  - The fate (stability, multiplication) of S. aureus, E. coli and E. faecalis was
      determined in three classes of recreational waters (seawater, estuarine, stream)
      supplemented with nutrients in the form of sewage and peptone. In the absence of
      sunlight (24 +/- 2 degrees C), all bacteria in all water samples did not multiply
      and were slowly (days) inactivated. When 50% sewage was added to all water
      samples, E. coli and E. faecalis multiplied but S. aureus did not. When peptone
      (0.05%, 0.5%) was the added nutrient, the three bacteria multiplied. In the
      presence of sunlight (15-27 degrees C), S. aureus was inactivated rapidly (hours)
      in all water samples. These results show that when their nutritional requirements
      are met, S. aureus, E. coli and E. faecalis can multiply in the high salinity
      conditions of seawater. However, under environmental conditions, sunlight is an
      effective natural bactericidal agent.

PMID- 17037150
TI  - Modelling faecal coliforms dynamics in the Seine estuary, France.
AB  - A model describing the dynamics of faecal coliforms (FC) in the Seine estuary has
      been developed and coupled with a three-dimensional hydrodynamic model. As input
      to this model three types of FC sources were considered: (1) FC transported by
      the Seine river flow at the estuary entrance at Poses dam; (2) FC brought in
      through the tributaries of the Seine estuary; and (3) the outfalls of the treated
      effluents of the WWTPs located along the estuary. As previous studies in the
      Seine estuary showed that a large proportion of FC was attached to SM, two pools
      of FC were considered separately in the model: free FC and FC attached to SM. Two
      main processes controlling the fate of FC in the estuary were considered:
      mortality and settling. The model calculates for a given discharge of the Seine
      river at Poses the longitudinal distribution of FC along the estuary. The model
      was validated by comparison of model calculations with experimental data in
      various hydrological conditions. The model also correctly reproduced the impact
      of the main river flow rate on the level of estuarine water's contamination.
      Finally, the model was used to test different scenarios of sanitation, suggesting
      priorities for sanitation efforts.

PMID- 17037151
TI  - Comparison of total and faecal coliforms as faecal indicator in eutrophicated
      surface water.
AB  - The aim of this study was to evaluate the use of total coliforms (TC) and faecal
      coliforms (FC) using a membrane filtration method for precise monitoring of
      faecal pollution in Korean surface water. The samples were collected in Korea
      from both main rivers and their tributaries. Presumptive TC * FC were enumerated.
      The ratios of presumptive FC to TC were not constant, but varied widely, and TC
      were difficult to enumerate because of overgrowth by background colonies. For FC
      this was not the case. Seven hundred and three purified strains of presumptive TC
      * FC and their background colonies were biotyped using API 20E. Among 272
      presumptive TC, non-faecal related species, Aeromonas hydrophila dominated
      (34.6%) and E. coli accounted for only 5.1%. In contrast, E. coli made up 89% of
      the 209 presumptive FC. Furthermore, of 164 background colonies on Endo Agar LES,
      54.9% was A. hydrophila, while background colonies on m-FC Agar were few (58
      strains), and despite their atypical colony appearance, most of them were
      biotyped as enteric bacteria. These results reveal that the detection of FC
      rather than TC using m-FC Agar is more appropriate for faecal pollution
      monitoring in eutrophicated surface water located in a temperate region.

PMID- 17037152
TI  - One-year monthly monitoring of Torque teno virus (TTV) in river water in Italy.
AB  - Torque teno virus (TTV) is prevalent worldwide in general populations but at
      present is not related with any specific pathology. Its presence in faeces and
      its remarkable environmental stability suggest the possibility of using it as an
      indicator of faecal contamination in the environment. To evaluate the waterborne
      spread of TTV and its possible relationship with human pathogen enteric viruses,
      water samples were collected monthly for a year (May 2004-April 2005) from a
      river receiving the effluent of the treatment plant of the city of Pisa,
      concentrated and assayed with bimolecular tests (PCR, RT-PCR). TTV was detected
      in three samples (25%) while 16% of samples were positive for enteroviruses, 33%
      for rotaviruses, 8% for noroviruses genotype 1 and 25% for noroviruses genotype
      2. Only two TTV samples (June and January) were also positive for rotavirus and
      norovirus, respectively. The detection of TTV in water confirmed its possible
      faecal-oral route of transmission but data are still insufficient to draw
      conclusions about the role of TTV as a viral indicator.

PMID- 17037153
TI  - Genotyping of single Cryptosporidium oocysts isolated from sewage and river
      water.
AB  - The study was designed to genotype individual Cryptosporidium oocysts using an
      18S rRNA gene-based semi-nested PCR and direct sequencing procedure. Positive PCR
      amplification was observed in all single C. parvum HNJ-1 oocyst samples tested.
      Semi-nested PCR and direct sequencing was applied to Cryptosporidium oocysts
      isolated from sewage and river water. The procedure could genotype 54% of FITC
      stained single oocysts isolated from sewage and 32% from river water. The
      predominant genotype in both sewage and river water was C. parvum genotype 1,
      accounting for 33 and 25%, respectively, of all the FITC-stained intact
      Cryptosporidium oocysts present.

PMID- 17037154
TI  - Monitoring of human enteric viruses and coliform bacteria in waters after urban
      flood in Jakarta, Indonesia.
AB  - Floodwaters in Kampung Melayu village, Jakarta, Indonesia, as well as river water
      and consumable water (including groundwater and tap water) samples in flooded and
      non-flooded areas, were quantitatively analysed to assess occurrence of viruses
      and total coliforms and E. coli as bacterial indicators after flooding event.
      High numbers of enterovirus, hepatitis A virus, norovirus (G1, G2) and adenovirus
      were detected at high concentration in floodwaters and waters sampled from
      Ciliwung River which runs across metropolitan Jakarta and is used widely for
      agriculture and domestic purposes by poor residents. One out of three groundwater
      wells in the flooded area was contaminated with all viruses tested while no
      viruses were found in groundwater samples in non-flooded areas and tap water
      samples. The results revealed that human enteric viruses, especially hepatitis A
      virus and adenovirus, were prevalent in Jakarta, Indonesia. This study suggested
      that flooding posed a higher risk of viral infection to the people through
      contamination of drinking water sources or direct contact with floodwaters.

PMID- 17037155
TI  - Detection and occurrence of antimicrobially resistant E. coli in groundwater on
      or near swine farms in eastern North Carolina.
AB  - The use of antibiotics for growth promotion and disease treatment by the
      commercial swine industry has led to high proportions of multiple antibiotic
      resistant enteric bacteria being shed by these animals and concerns about the
      environmental spread of these bacteria. A study was conducted to quantify the
      extent of release of antibiotic-resistant E. coli from swine farms into
      groundwater. Four study sites, two swine farms and two reference sites (crop
      farms), with known groundwater flow paths were screened for E. coli four times
      over the course of one and a half years. A total of 100 biochemically-confirmed
      E. coli were collected from the four sites. There were statistically
      significantly higher E. coli levels at the two swine farm sites than at the
      reference sites. The bacterial isolates were tested for antibiotic resistance
      using a panel of 17 drugs that are typical of human and veterinary use. There
      were 19 and 71 E. coli isolates from swine farms #1 and #2, respectively, with
      most (68%) being resistant to 1 -6 antimicrobials. Only one E. coli isolate from
      each of the reference sites showed antimicrobial resistance traits. The results
      of this study demonstrate that antibiotic-resistant E. coli strains are present
      in groundwaters of swine farms with a typical lagoon and land application system
      for waste management.

PMID- 17037156
TI  - Hybridisation of F+ RNA coliphages detected in shellfish samples with
      oligonucleotide probes to assess the origin of microbiological pollution of
      shellfish.
AB  - Current measures for controlling the public health risks associated with bivalve
      molluscan shellfish consumption rely on the use of Escherichia coli to indicate
      the sanitary quality of shellfish harvesting areas. However, it has been
      demonstrated that E. coli is an inadequate indicator of the viral risk associated
      with shellfish. An alternative indicator, male-specific B+ coliphages, have been
      investigated as viral indicators of faecal contamination that may provide source
      specific information for impacted environmental waters. This study compared the
      distribution of E. coli and F+ RNA bacteriophages in shellfish grown in
      harvesting areas of Greece and also examined the presence and proportions of the
      different subgroups of F+ RNA coliphages in shellfish. F+ RNA bacteriophages were
      present in shellfish at higher concentrations than E. coli. Elevated numbers of
      F+ RNA bacteriophages observed in the winter concur with the known increased
      viral risk associated with shellfish harvested at that time of year in Greece.
      The majority of F+ RNA coliphages detected in shellfish samples belonged to group
      IV which indicated the possible presence of animal faecal material in sample
      harvesting areas. Phages of groups II and III (human waste and human faecal
      material, respectively) were present at low levels. Finally, 8% of the phages
      hybridised were found to belong to group I. The presence of group IV showed
      seasonal distribution (more in winter, less in summer) whereas the other groups
      did not show any difference. Monitoring of F+ coliphage subgroups may indicate
      the presence and major sources of microbial inputs to surface waters; however,
      environmental effects on the relative occurrence of different groups need to be
      considered.

PMID- 17037157
TI  - Effects of rainfall on the occurrence of human adenoviruses, total coliforms, and
      Escherichia coli in seawater.
AB  - A two-month survey was conducted in order to evaluate the effects of rainfall on
      the fate of microorganisms in seawater in the Tokyo Bay, Japan. The seawater
      sample (1,000 mL) was applied to a method to concentrate virus, followed by a
      quantification of human adenoviruses using the real-time PCR. Total coliforms and
      E. coli, which were determined by the colony forming method, were detected in all
      47 seawater samples, while human adenoviruses were detected in 38 (81%) of the
      samples. The concentration of tested microorganisms showed 1-2 log units increase
      after rainfall events, followed by the gradual decrease to the level before the
      rainfall within a few days.

PMID- 17037158
TI  - Endemic Cryptosporidium infection and drinking water source: a systematic review
      and meta-analyses.
AB  - Cryptosporidium is a well-known cause of diarrhoea in humans. Little is known
      about risk factors associated with endemic cryptosporidiosis, which constitutes
      the majority of cases. We carried out meta-analyses to verify if drinking water
      is also associated with endemic infection and to assess the magnitude of the
      associations. The global meta-analysis suggests that there is an increased risk
      of Cryptosporidium infection among unsafe water users (OR 1.40 [1.15, 1.72]).
      Studies were stratified, according to the exposure to different sources of safe
      drinking water, due to the heterogeneity presented. The consumption of non-well
      and unboiled water was associated with an increased chance of endemic
      cryptosporidiosis, though only the latter was significant (OR 1.45 [0.95, 2.20];
      OR 1.61 [1.09, 2.38]). Drinking non-bottled water did not present a risk factor
      associated with endemic cryptosporidiosis (OR 0.87 [0.72, 1.05]). These meta
      analyses present results that could be useful to clarify the epidemiology of
      Cryptosporidium. We recommend that other risk factors could also be studied by
      this approach.

PMID- 17037159
TI  - Epidemiological surveillance of human enteric viruses by monitoring of different
      environmental matrices.
AB  - In the aim of studying possible relations between viruses detected in clinical
      specimens and the ones found in different environmental matrices, in the period
      May 2004 to April 2005, the collection of faecal samples from gastroenteritis
      cases and the monthly monitoring of raw and treated wastewater, river water,
      seawater and mussels were carried out. The viruses considered for environmental
      monitoring were adenovirus, rotavirus, enterovirus, norovirus, hepatitis A virus
      (HAV) and Torque teno virus (TTV): they were searched for with PCR and RT-PCR and
      confirmed by gene sequencing. Faecal coliforms and somatic coliphages' counts
      were also determined. The surveillance of case detected 45 positive faecal
      samples out of 255 (17.6%) while 35 of 56 environmental samples (62.5%) resulted
      positive for at least one of the considered viruses. The detection of the same
      viral strain in the faeces of gastroenteritis cases and in water was possible for
      adenovirus and rotavirus, which were also predominant in environmental matrices;
      thus they could be considered as a reference for risk assessment.

PMID- 17037160
TI  - Microbial exposure assessment of an urban recreational lake: a case study of the
      application of new risk-based guidelines.
AB  - New WHO and Australian guidelines promote a risk-management approach for
      minimising exposure to pathogens in recreational waters. Between 2003 and 2005,
      they were applied to Lake Parramatta (10 ha, 450 ML), a potential recreation site
      in Sydney, Australia. A three stage approach was developed involving (1) initial
      suitability assessment using historic data, (2) revised suitability assessment
      based on new data and (3) characterisation of hazardous (especially wet weather)
      events. Contrary to the stage 1 suitability classification, stage 2 baseline data
      indicated that during dry weather the lake had water quality sufficient for
      primary contact recreation (95th percentiles for enterococci = 19 MPN/100, n =
      50) and the major pathogen source was wildfowl. Guideline principles provided a
      rationale for collecting microbiological and geographic data needed to understand
      local cycles of lake contamination/recovery. The concept of hazardous events was
      particularly useful. Studies of stormwater events led us to identify a transition
      point (> 10 mm rainfall in 24 h) where human-faecal pathogen risks increased and
      access needed to be controlled. Together baseline and event data yielded
      operational tools (i.e. event detection methods, action triggers, auditing
      criteria, remediation priorities) for minimising bather exposure.

PMID- 17037161
TI  - Microbial risk and removal--a utility perspective.
AB  - In this paper the results of a sampling programme, undertaken as part of the EU
      MicroRisk project, are described. This project was undertaken to ascertain the
      occurrence of pathogens and indicators in the River Thames and their subsequent
      removal through a treatment works. Appropriate physico-chemical surrogates, as
      determined by statistical correlation are proposed for the microorganisms
      identified in the raw water. This study shows that under normal raw water
      conditions the treatment works is able to remove microbial contamination with a
      significant margin of safety.

PMID- 17037162
TI  - Pathogen monitoring offers questionable protection against drinking-water risks:
      a QMRA (quantitative microbial risk analysis) approach to assess management
      strategies.
AB  - Risk mitigation provided by human monitoring and control over a water supply
      system has been consistently overlooked when estimating pathogen exposure to
      consumers. The Systems-Actions-Management (SAM) framework lends itself neatly to
      Quantitative Microbial Risk Assessment (QMRA) as one way to establish this link.
      The general premise is that an organisational protocol will influence how a human
      controller behaves, in turn influencing the system performance. For illustrative
      purposes, the framework was applied to a hypothetical water supply system to
      quantify the risk reduction offered by routine Cryptosporidium monitoring and the
      response to oocyst 'detects'. Our findings suggest that infrequent direct
      pathogen monitoring may provide a negligible risk barrier. The practice of
      sampling treated water to verify microbiological integrity is also dubious:
      oocyst densities were largely under-estimated, in part due to the spatial
      dispersion of oocysts in the waterbody, but predominantly from imperfect
      detection methods. The development of 'event-driven' monitoring schemes with
      barrier performance-based treatment verification methods, as promoted in new
      guidelines, is supported as a pressing issue to reduce the likelihood of
      undetected pathogen passage through a treatment plant.

PMID- 17037163
TI  - Microbial risk assessment of dental unit water systems in general dental practice
      in Greece.
AB  - Water was sampled from source water, the 3-in-1 syringe and the air rotor water
      line of dental unit water systems (DUWS) in general dental practice in Attica,
      Greece. A section of the water line supplying the 3-in-1 syringe was cut for
      biofilm analysis. High total viable counts, Mycobacterium spp. and Pseudomonas
      aeruginosa were detected in the samples. Back siphonage was evidenced by the
      presence of blood and the recovery of oral anaerobes from the samples. Legionella
      pneumophila was recovered from 16.1% of biofilm samples. All tested disinfectants
      reduced the total viable counts of the DUWS to < 100 CFU/mL.

PMID- 17037164
TI  - A review of ADM1 extensions, applications, and analysis: 2002-2005.
AB  - Since publication of the Scientific and Technical Report (STR) describing the
      ADM1, the model has been extensively used, and analysed in both academic and
      practical applications. Adoption of the ADM1 in popular systems analysis tools
      such as the new wastewater benchmark (BSM2), and its use as a virtual industrial
      system can stimulate modelling of anaerobic processes by researchers and
      practitioners outside the core expertise of anaerobic processes. It has been used
      as a default structural element that allows researchers to concentrate on new
      extensions such as sulfate reduction, and new applications such as distributed
      parameter modelling of biofilms. The key limitations for anaerobic modelling
      originally identified in the STR were: (i) regulation of products from glucose
      fermentation, (ii) parameter values, and variability, and (iii) specific
      extensions. Parameter analysis has been widespread, and some detailed extensions
      have been developed (e.g., sulfate reduction). A verified extension that
      describes regulation of products from glucose fermentation is still limited,
      though there are promising fundamental approaches. This is a critical issue,
      given the current interest in renewable hydrogen production from carbohydrate
      type waste. Critical analysis of the model has mainly focused on model structure
      reduction, hydrogen inhibition functions, and the default parameter set
      recommended in the STR. This default parameter set has largely been verified as a
      reasonable compromise, especially for wastewater sludge digestion. One criticism
      of note is that the ADM1 stoichiometry focuses on catabolism rather than
      anabolism. This means that inorganic carbon can be used unrealistically as a
      carbon source during some anabolic reactions. Advances and novel applications
      have also been made in the present issue, which focuses on the ADM1. These papers
      also explore a number of novel areas not originally envisaged in this review.

PMID- 17037165
TI  - Implementing ADM1 for plant-wide benchmark simulations in Matlab/Simulink.
AB  - The IWA Anaerobic Digestion Model No.1 (ADM1) was presented in 2002 and is
      expected to represent the state-of-the-art model within this field in the future.
      Due to its complexity the implementation of the model is not a simple task and
      several computational aspects need to be considered, in particular if the ADM1 is
      to be included in dynamic simulations of plant-wide or even integrated systems.
      In this paper, the experiences gained from a Matlab/Simulink implementation of
      ADM1 into the extended COST/IWA Benchmark Simulation Model (BSM2) are presented.
      Aspects related to system stiffness, model interfacing with the ASM family, mass
      balances, acid-base equilibrium and algebraic solvers for pH and other
      troublesome state variables, numerical solvers and simulation time are discussed.
      The main conclusion is that if implemented properly, the ADM1 will also produce
      high-quality results in dynamic plant-wide simulations including noise, discrete
      sub-systems, etc. without imposing any major restrictions due to extensive
      computational efforts.

PMID- 17037166
TI  - Activity corrections for ionization constants in defined media.
AB  - Correcting ionization constants for activity effects can have a larger impact on
      some ionic species than correcting for temperature effects. Computer trials
      compared two pH calculation methods, and showed that an interpolation algorithm
      found a precise charge balance quickly but was unstable under certain conditions,
      while a slower pH search method was stable under all test conditions. The optimal
      calculation strategy was a hybrid of these two approaches. The hybrid calculation
      method is stable, quick, includes activity and temperature corrections, does not
      need kinetic rate constants, allows all known ionic species to be included, and
      allows for easy addition of new chemical species.

PMID- 17037167
TI  - Identifiability study of the proteins degradation model, based on ADM1, using
      simultaneous batch experiments.
AB  - The objective of the present study is to analyse kinetic and stoichiometric
      parameter values of gelatine anaerobic degradation at thermophilic range, based
      on an experiment designed to elucidate if volatile fatty acids (VFA) are
      inhibitors of the hydrolysis process. Results showed that VFA are not inhibiting
      the hydrolysis process. The ADM1 model adequately expressed the consecutive steps
      of hydrolysis and acidogenesis, with estimated kinetic values corresponding to a
      fast acidogenesis and slower hydrolysis. The hydrolysis was found to be the rate
      limiting step of anaerobic degradation. Estimation of yield coefficients based on
      the relative initial slopes of VFA profiles obtained in a simple batch experiment
      produced satisfactory results. From the identification study, it was concluded
      that it is possible to determine univocally the related kinetic parameter values
      for protein degradation if the evolution of amino acids is measured in
      simultaneous batch experiments, with different initial protein and amino acids
      concentrations.

PMID- 17037168
TI  - An extension of the Anaerobic Digestion Model No. 1 to include the effect of
      nitrate reduction processes.
AB  - Nitrate reduction processes were incorporated into the IWA Anaerobic Digestion
      Model No. 1 (ADM1) in order to account for the effect of such processes on
      fermentation and methanogenesis. The general structure of the ADM1 was not
      changed except for modifications related to disintegration and hydrolysis of
      complex organic matter and decayed biomass. A fraction of butyrate/valerate and
      propionate degraders was assumed to be the fermentative denitrifiers carrying out
      fermentation in the absence of N-oxides. Nitrate reduction proceeded in a
      stepwise manner to nitrite, nitric oxide, nitrous oxide and nitrogen gas using
      four substrates as electron and/or carbon source. The utilization of the four
      substrates and N-oxides was based on stoichiometry and kinetics. The inhibitory
      effect of N-oxides on the methanogens was accounted for by the use of non
      competitive inhibition functions. Model simulations were compared with
      experimental data obtained with a batch, mixed fermenting and methanogenic
      culture amended with various initial nitrate concentrations.

PMID- 17037169
TI  - Critical analysis of some concepts proposed in ADM1.
AB  - The Anaerobic Digestion Model No. 1 (ADM1) has been developed by the expert task
      group of the IWA to establish a common platform for simulation of a wide variety
      of anaerobic degradation processes. It enables comparison of different methods
      and parameter values for description of specific sub-processes, with the methods
      and default values proposed by the task group. This will hopefully stimulate a
      more structured discussion on anaerobic digestion modelling compared to the
      recent past, when many different researchers developed a slightly different model
      and it remained largely unclear what could, and what could not be compared. In
      this paper we take the liberty to criticize some aspects of ADM1 and its
      implementation, as we think they represent concepts that are too easily
      extrapolated from activated sludge models. The specific subjects discussed here
      are the COD-based description of the reaction stoichiometry (i), the widely
      adopted use of a constant value for the solid retention time high-rate anaerobic
      bioreactors (ii), and the kinetic description of the acetogenic reactions as
      proposed in ADM1 (iii).

PMID- 17037170
TI  - Use of the ADM1 to investigate the effects of acetoclastic methanogen population
      dynamics on mesophilic digester stability.
AB  - The ADM1 was employed to assess the effect of variations in solids hydrolysis and
      acetoclastic methanogen process characterizations on municipal digester stability
      relating to excess acetate utilization capacity. First-order single- and dual
      pathway hydrolysis rate functions and single and competitive acetoclastic
      methanogen rate functions were implemented in the ADM1. The acetate capacity
      number (ACN), defined as the ratio between the maximum acetate utilization rate
      and the average acetate production rate, was used to index digester instability.
      Simulations of a single CSTR at steady state indicate a similar ACN can be
      obtained with a 12-day SRT digester dominated by Methanosarcina sp and a 24-day
      SRT digester dominated by Methanosaeta sp. An increase in ACN with a decrease in
      SRT representing Methanosarcina sp. selection was observed for particulate feed
      loadings from 40 g COD/L to 90 g COD/L. Feeding frequency and dual-pathway
      hydrolysis were found to have less effect on the ACN than the competitive
      acetoclastic model structure.

PMID- 17037171
TI  - Description of nitrogen incorporation and release in ADM1.
AB  - ADM1 represents a universally applicable biokinetic model for the mathematical
      description of anaerobic digestion of different types of organic substrates.
      Digestion of particulate composites is described as a five-stage process
      involving disintegration, hydrolysis, acidogenesis, acetogenesis and
      methanogenesis, of which the last three process steps are represented by growth
      kinetics of the specific degrading biomass. Decay of the produced biomass
      according to ADM1 is depicted by a recycle mass flux to the composite particulate
      substrate. Consequently two different actions are lumped into one process
      describing both conversion of feed substrate (depending primarily on influent
      characterisation) and generation of decay products (depending on digestion
      performance). In this presentation the introduction of a separate compound of
      inert decay products in analogy to ASM1 is suggested. Model calibration of
      separately monitored digestion of primary and secondary sludge (nitrogen content
      0.030 g N/g TSS and 0.051 g N/g TSS, respectively) reveals the advantage of a
      clear distinction of disintegration and decay. The fate of nitrogen in the course
      of incorporation and release (0.016 g N/g TSS compared to 0.028 g N/g TSS) during
      digestion processes is comprehensible and the final ammonia concentration in the
      rejection water becomes predictable.

PMID- 17037172
TI  - Applications and limitations of ADM 1 in municipal wastewater solids treatment.
AB  - The ADM 1 model has been implemented in a steady-state whole wastewater plant
      simulator. The ADM 1 model has been in use with good success for approximately 2
      years on a wide range of wastewater treatment facilities. However, a number of
      modifications were necessary to allow it to be used in the context of municipal
      wastewater treatment. It was found that the model's use was greatly simplified if
      used in conjunction with a larger plant simulator to assist in the feed
      fractionation. It was also found that a better fit to actual operating data was
      achieved if some of the slowly biodegradable particulate fraction was partitioned
      into ADM particulate fractions other than the composite fraction. Another
      significant limitation of the model is in the absence of phosphorus modeling. The
      ADM model needs to have phosphorus handling for all the relevant fractions, and
      needs to include the handling of inorganic reactions such as struvite
      precipitation and metal phosphate/metal hydroxide precipitation. Activity effects
      on chemical equilibria are significant when considering phosphorus. Also of
      importance in wastewater treatment is the fate of sulfur compounds. This includes
      the generation of H2S in the digester gas and the fate of the sulfur species in
      the digested sludge (as a predictor of odour-generating potential).

PMID- 17037173
TI  - An approach for substrate mapping between ASM and ADM1 for sludge digestion.
AB  - Kinetic modelling of the hydrolysis stage of municipal activated sludge, which is
      presumed to be the rate-limiting step in the anaerobic sludge digestion process,
      was studied by measuring methane production rate (MPR) in anaerobic batch tests.
      The MPR curves revealed that the degradable organic components in municipal
      sludge could be classified into two fractions having different kinetics. The
      first fraction (XS1) constituted about 55% of the sludge COD and degraded with
      first-order kinetics. The second fraction (XS2), which degraded during the
      initial phase, accounted for about 21% of sludge COD. The degradation kinetics
      for XS2 was expressed by Contois-type equation with respect to concentration of
      substrate in the fed sludge and that of active biomass in the mixture.
      Simultaneous batch aerobic respirometric tests showed that the activated sludge
      was composed of 53% heterotrophic biomass (XH-Aerobe) COD and 20% of slowly
      biodegradable COD (XS), that had same kinetic expressions as observed in the
      batch anaerobic tests. The observed correlation between substrate fractions
      suggests XS1 and XS2 could be directly mapped to the aerobic state variables of
      XH-Aerobe and Xs respectively. The degradation of XS1 seems to be anaerobic decay
      of XH-Aerobe while XS2 is thought to be hydrolysis of XS by microcosm of the
      sludge.

PMID- 17037174
TI  - ADM1 application for tuning and performance analysis of a multi-model observer
      based estimator.
AB  - Anaerobic digestion model no.1 (ADM1) was used for tuning and performance
      analysis of the multi-model observer based estimator (mmOBE). The mmOBE was based
      on the variable structure model (VSM) of the anaerobic digestion model, which
      consists of several local submodels, each of which describes a typical process
      state. Depending on the hydraulic retention time, ADM1 simulated the
      methanogenic, organic overload, and acidogenic states of the process. These
      simulations allowed for optimising tunable parameters of the mmOBE. Owing to
      relatively slow process dynamics, a data acquisition interval as large as one day
      was sufficient to obtain acceptable accuracy. The simulations of mmOBE
      performance showed excellent rate of mmOBE convergence to ADM1 outputs. Moreover,
      mmOBE successfully estimated key kinetic parameters, such as maximal
      transformation rates of CODs, VFAs, and methane. These estimations can be used in
      the development of the advanced knowledge-based process system, which uses both
      available measurements and estimations of key kinetic parameters for extended
      diagnosis of failures and process trend analysis.

PMID- 17037176
TI  - Modifying ADM1 to include formation and emission of odourants.
AB  - A mathematical model that is based upon the ADM1 structure has been developed to
      describe the formation and emission of odourous compounds in anaerobic sludge
      digestion. Special emphasis is given to the general mechanisms for the formation
      of common odorous sulfur compounds that are found in anaerobic digesters: methyl
      mercaptan, dimethyl sulfide and hydrogen sulfide, as well as volatile fatty acids
      and ammonia. The model includes multiple-reaction stoichiometry, microbial growth
      kinetics and conventional material balances for an ideally mixed reactor.
      Simulations that were performed with the model revealed that changes in common
      operational parameters such as temperature, HRT and sludge metal content can
      dramatically impact upon the gas phase concentrations of odourants. Additional
      research is required to reduce uncertainty in the model formulation.

PMID- 17037175
TI  - Variable stoichiometry with thermodynamic control in ADM1.
AB  - The effect of a variable stoichiometry of the carbohydrate fermentation process
      in the IWA Anaerobic Digestion Model No.1 (ADM1) is investigated. Most existing
      anaerobic digestion models including ADM1 consider a fixed-stoichiometry for
      their conversion processes. The ADM1 model was first transformed into an only mol
      based model to remove some errors derived from the mixed COD-mol based standard
      model and to allow for implementation of the variable stoichiometry.
      Consequently, the values of the butyrate and acetate catabolic yields of
      carbohydrate fermentation are made dependent on the hydrogen concentration and
      the reactor pH according to the predictions of a recently developed mixed culture
      fermentation model based on thermodynamic considerations. The simulation results
      obtained showed no significantly different responses in terms of effluent quality
      and system robustness between the standard and the variable stoichiometry ADM1
      under overload conditions, and for both single- and two-step anaerobic digestion
      configurations. This behaviour is explained by the non-limiting acetogenic
      activity that compensated for the changes in the acidogenic products, typical
      behaviour for serial processes close to equilibrium. Based on the results
      obtained, thermodynamic rather than kinetic control for these conversions is
      suggested. Depending on the objectives to be met, lumping of carbohydrate
      fermenters and oxidative acetogens into a single biomass group with a variable
      stoichiometry is proposed for further consideration.

PMID- 17037177
TI  - Simulation of DEHP biodegradation and sorption during the anaerobic digestion of
      secondary sludge.
AB  - Di-ethylhexyl phthalate (DEHP) has commonly been found in the sludge of municipal
      wastewater treatment plants especially during anaerobic processing. It is slowly
      biodegradable under anaerobic conditions. Due to its high hydrophobicity,
      sorption-desorption processes can be rate-limiting for the compound
      biodegradation. In this study, the anaerobic biodegradation of DEHP was
      investigated through batch kinetic experiments and dynamic transitions of a
      continuous stirred tank reactor (CSTR) fed with secondary sludge contaminated
      with DEHP. A widely accepted model (ADM1) was used to fit the anaerobic digestion
      of secondary sludge and was properly extended to account for DEHP removal, in
      which mass transfer processes are also involved. It was shown that DEHP removal
      was limited by the transfer of DEHP within the solid fraction. The criterion
      selected for the distinction of the two sites was whether the compound sorbed in
      those sites was bioavailable for biodegradation or not. Thus, the aqueous phase
      and the surface of the biosolids were considered as suitable sites for the
      compound to be bioavailable and the main bulk of the solid matrix was regarded as
      sites, where the compound remains "protected" against biodegradation. The model,
      fitted to the batch experimental data, was able to predict DEHP removal in the
      CSTR operated at various HRTs.

PMID- 17037178
TI  - Modelling anaerobic digestion acclimatisation to a biodegradable toxicant:
      application to cyanide.
AB  - The observed acclimatisation to biodegradable toxicants in anaerobic cassava
      wastewater treatment is explained by modelling anaerobic cyanide degradation. A
      complete degradation pathway is proposed for cyanide. Cyanide degradation is
      modelled as enzymatic hydrolysis to formate and ammonia. Ammonia is added to the
      inorganic nitrogen content of the digester while formate is degraded by the
      hydrogenotrophic methanogens. Cyanide irreversible enzyme inhibition is modelled
      as an inhibition factor to acetate uptake processes. Cyanide irreversible
      toxicity is modelled as a decay factor to the acetate degraders. Cyanide as well
      as added phosphorus buffer solution were considered in the chemical equilibrium
      calculations of pH. The observed reversible effect after acclimatisation of
      sludge is modelled by a population shift between two aceticlastic methanogens
      that have different tolerance to cyanide toxicity. The proposed pathway is added
      to the IWA Anaerobic Digestion Model no.1 (ADM1). The ADM1 model with the
      designed extension is validated by an experiment using three lab-scale upflow
      anaerobic sludge bed reactors which were exposed to different cyanide loadings.

PMID- 17037179
TI  - Parameter analysis of the IWA Anaerobic Digestion Model No. 1 for the anaerobic
      digestion of blackwater with kitchen refuse.
AB  - The IWA anaerobic digestion model No.1 (ADM1) had been successfully applied to
      the lab-scale mesophilic blackwater anaerobic digestion (BWAD) plant for cases of
      only blackwater (BW) feeding and of BW plus kitchen refuse (KR) feeding. In this
      paper, the simulation results of BW + KR anaerobic digestion are presented and
      discussed, followed by the analyses and discussion of the critical and important
      parameters as well as the performance of ADM1 based on these results. The raw BW
      can contain up to 30% short chain fatty acids (SCFA) which severely impact the
      performance of the model. The model proved that the disintegration/hydrolysis
      rate of BW is around 4.5 d(-1), which is about ten times higher than that of KR
      (Kdis,KR = 0.5 d(-1)). ADM1 is not sensitive to the distribution ratio among
      carbohydrates, proteins and lipids. For BWAD the C4 metabolism can be integrated
      in the uptake of LCFA. The uptake delay phenomenon was observed and cannot be
      simulated by ADM1, but it is tolerable. No unique KI,NH3,ac is found out for all
      investigated ammonia concentration ranges. Meanwhile, ADM1 is not sensitive to
      KLa and kp1 so they can easily be set up.

PMID- 17037180
TI  - Application of ADM1 for the simulation of anaerobic digestion of olive pulp under
      mesophilic and thermophilic conditions.
AB  - The management of the wastewater originating from olive oil producing industries
      poses a serious environmental problem. Recently, two-phase production of olive
      oil has been developed, leading to almost complete elimination of the bulk of the
      generated wastewater and, is thus regarded as an environmentally friendly
      technology. However, the main waste stream (olive pulp) is a slurry material
      characterized by high solids concentration (approximately 30%), requiring
      stabilisation before its final disposal. The anaerobic digestion of olive pulp is
      studied in this work under mesophilic and thermophilic conditions in CSTR-type
      digesters. The digesters were fed with water-diluted (1:4) olive pulp at an HRT
      of 20 days and an OLR of 3.94 kg COD m(-3) d(-1). In order to study the process
      kinetics, the digesters were subjected to impulse disturbances of different
      substrates. The IWA anaerobic digestion model was used to simulate the reactors'
      response. Some key process parameters, such as the specific maximum uptake rate
      constants and the saturation constants for the volatile fatty acids degradation
      were estimated and compared with the standard values suggested by the ADM1.

PMID- 17037181
TI  - ADM1-based methodology for the characterisation of the influent sludge in
      anaerobic reactors.
AB  - This paper presents a systematic methodology to characterise the influent sludge
      in terms of the ADM1 components from the experimental measurements traditionally
      used in wastewater engineering. For this purpose, a complete characterisation of
      the model components in their elemental mass fractions and charge has been used,
      making a rigorous mass balance for all the process transformations and enabling
      the future connection with other unit-process models. It also makes possible the
      application of mathematical algorithms for the optimal characterisation of
      several components poorly defined in the ADM1 report. Additionally, decay and
      disintegration have been necessarily uncoupled so that the decay proceeds
      directly to hydrolysis instead of producing intermediate composites. The proposed
      methodology has been applied to the particular experimental work of a pilot-scale
      CSTR treating real sewage sludge, a mixture of primary and secondary sludge. The
      results obtained have shown a good characterisation of the influent reflected in
      good model predictions. However, its limitations for an appropriate prediction of
      alkalinity and carbon percentages in biogas suggest the convenience of including
      the elemental characterisation of the process in terms of carbon in the
      analytical program.

PMID- 17037182
TI  - Waste characterization for implementation in ADM1.
AB  - Wastewater characterization as required for implementation in ADM1 is based on
      the identification of the numerous concentrations of the specific compounds
      defined in ADM1. However, identification of the individual substrate
      concentrations requires specific analytical techniques and in most cases only
      general measurements like COD, TOC, and organic nitrogen are available. This
      paper describes a simple method for calculation of the lumped elemental
      composition of the organic substrates in the wastewater from a limited number of
      widely available analyses. Using the elemental composition of the lumped
      substrate and the elemental composition of the substrates defined in the model,
      the influent composition as required for input in ADM1 can be calculated.
      Furthermore, proper waste characterization allows for an initial analysis of the
      biogas flow rate and composition as well as the reactor pH that can be achieved
      upon organic substrate degradation, as will be demonstrated. It is hoped that the
      methods described in this paper will stimulate and simplify future application of
      ADM1.

PMID- 17037183
TI  - Enteral sedation for the dental practice.

PMID- 17037184
TI  - Oral pathology quiz #52. Case number 1. Squamous cell carcinoma.

PMID- 17037185
TI  - A tale of two officers: life in the Dental Corps.

PMID- 17037186
TI  - The marketplace for selling your practice.

PMID- 17037187
TI  - Blood pressure monitoring in the dental setting.

PMID- 17037188
TI  - [Progresses in the structure and function of Kazal-type proteinase inhibitors].
AB  - Proteinase inhibitors are widely distributed in many living organisms and play
      crucial roles in many biological processes, particularly in regulating the
      proteinase activity spatially and temporally. However, The Kazal family of serine
      protease inhibitors is one of the most important and extensively studied protease
      inhibitor families. This type of protease inhibitor normally consists of one or
      several domains. Every domain has a highly conserved sequence structure and
      molecular conformation. It is found that contact residues are hyper variable,
      which are responsible for the interaction of inhibitors and proteinases. Most of
      them are in the solvent exposed loop. But P1 residue is the key active site of
      the interaction between inhibitor and enzyme. The types of the amino acid at P1
      site likely play an important role in causing different inhibitory activity. The
      substitutions at the contact residues cause significant effects on the
      association constant. By using the Laskowski algorithm, the Ki values of a Kazal
      domain against six serine proteinases can be predicted from the domain' s
      sequence alone. At present there are many Kazal proteinase inhibitors found in
      the organisms, which show important biological functions. This article gives a
      comprehensive review of the newer developments in the characters and the
      interaction of the Kazal-type inhibitors.

PMID- 17037189
TI  - [Identification of mimotope peptides which bind to the SARS-CoV spike protein
      specific monoclonal antibody 2C5 with phage-displayed peptides library].
AB  - To identify the epitope of SARS-CoV spike protein specific neutralizing
      monoclonal antibody (MAb) 2C5. The antibody was used as target and three rounds
      of bio-panning were conducted with phage-display peptide library. After the third
      panning, 20 phage-plague clones were randomly picked and analyzed for the binding
      ability with the MAb 2C5 by ELISA. The display sequence analysis demonstrated
      that among the twenty phage clones, eight clones displayed the same seven-peptide
      TPEQQFT. All these eight phage-clones showed strongest binding activity with 2C5
      in phage ELISA analysis. Furthermore, phages displaying peptide TPEQQFT could
      specifically inhibit the binding of MAb 2C5 with SARS-CoV spike protein. The
      results demonstrated that TPEQQFT is a mimic epitope peptide containing
      neutralizing MAb 2C5. This study may provide information for further structural
      and functional analysis of spike protein and development vaccine for severe acute
      respiratory syndrome.

PMID- 17037190
TI  - [Organization and transcription strategy of genome of Bombyx mori bidensovirus
      (China isolate) VD1].
AB  - To better understand the genomic structure and function of Bombyx mori
      bidensovirus (China isolate) VD1, the VD1 was purified and cloned into the pUC119
      vector, and the complete nucleotide sequence of VD1 was determined. Sequence
      analysis showed that VD1 genome consisted of 6543 nts including inverted terminal
      repeats (ITRs) of 224 nts. In the viral genome, three major open reading frames
      (ORF1, ORF2 and ORF3) in the plus strand and one major ORF (ORF4) in the
      complementary strand were identified. Comparison of the complete genome sequence
      between Bombyx mori bidensovirus (China isolate) and BmDNV-2 (Yamanashi isolate)
      showed an identity of 98.4% in VD1, with a total number of 104 bp substitutions
      and 1 bp insertions found in Bombyx mori bidensovirus (China isolate), the highly
      variable regions were mainly located in VD1 ORF3 and VD1 ORF4. Northern blotting
      revealed that VD1 contained 1.1 kb and 1.5 kb transcript in the left-half 'plus'
      strand, and one transcript about 3.3 kb of 'minus' strand in the right-half.
      Sequencing of 3' and 5' ends of transcript products showed the 1.1 kb transcript
      started at nt 290 and ended at nt 1437, the 1.5 kb transcript was found to start
      nt 1423 and ended at 2931, and the 3.3 kb transcript was found to start nt 6287
      and ended at nt 2922. Therefore, the 1.5 kb transcript in the left-half plus'
      strand and 3.3 kb transcripts of minus' strand in the right-half overlapped for
      10 nts at the 3' ends. These results indicate that this virus employs a
      transcription strategy that is radically different from that of the other
      reported DNVs.

PMID- 17037191
TI  - [The construction of recombinant adenovirus expressing bifunctional fusion
      protein sCAR-EGF and the detection of its activity].
AB  - To improve the targeting of adenovirus vector for gene therapy, a fusion gene
      sCAR-EGF, in which epidermal growth factor gene was fused to the 3' end of
      extracellular Coxsackie virus-adenovirus receptor gene, was constructed and
      cloned into shuttle plasmid pDC315 to obtain a recombinant plasmid pDC315-sCAR
      EGF. With the AdMax system, AD-293 cells were co-transfected with pDC315-sCAR-EGF
      and adenovirus genomic plasmid pBHGloxdeltaE13cre. Through high efficiency site
      specific recombination, a replication-defective adenovirus Ad5-CMV-sCAR-EGF was
      constructed. The recombinant adenovirus was analyzed by PCR and Western blotting,
      the results indicated that Ad5-CMV-sCAR-EGF contained the fusion gene sCAR-EGF,
      and the adenovirus infected cells was induced to produce and secrete the fusion
      protein into the supernatant. We have demonstrated that the fusion protein sCAR
      EGF is helpful for elevating the infection efficiency of Ad5-CMV-luc with the
      reporter gene in vitro, which providing a new approach to the gene therapy for
      tumors overexpressing EGFR.

PMID- 17037192
TI  - [Generation high yield vaccine strain wholly derived from avian influenza viruses
      by reverse genetics].
AB  - Highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtypes caused
      enormous economical loss to poultry farms in China and Southeastern Asian
      countries. The vaccination program is a reliable strategy in controlling the
      prevalence of these disastrous diseases. The six internal genes of the high-yield
      influenza virus A/Goose/Dalian/3/01 (H9N2), the hemagglutinin (HA) gene of
      A/Goose/HLJ/QFY/04 (H5N1) strain, and the neuraminidase gene from
      A/Duck/Germany/1215/73 (H2N3) reference strain were amplified by RT-PCR
      technique. The HA gene was modified by the deletion of four basic amino acids of
      the connecting peptide between HA1 and HA2. Eight gene expressing plasmids were
      constructed, and the recombinant virus rH5N3 was generated by cells transfection.
      The infection of chicken embryos and the challenge tests involving chickens
      demonstrated that the recombinant H5N3 (rH5N3) influenza virus is avirulent. The
      allantoic fluids of rH5N3-infected eggs contain high-titer influenza viruses with
      hemagglutination unit of 1:2048, which are eight times those of the parental H5N1
      virus. The rH5N3 oil-emulsified vaccine could induce hemagglutination inhibition
      (HI) antibodies in chickens in 2 weeks post-vaccination, and maximum geometric
      mean HI-titer were observed 4 approximately 5 weeks post-vaccination and were
      kept under observation for 18 weeks. The rH5N3-vaccinated chickens were fully
      protected against morbidity and mortality of the lethal challenge of the H5N1
      HPAI viruses, A/Goose/Guangdong/1/96 and A/Goose/HLJ/QFY/04, which had 8 years
      expansion and differences among multiple amino acids in HA protein. The N3
      neuraminidase protein marker makes it possible to distinguish between H5N1
      infected- and H5N3 vaccinated animals.

PMID- 17037193
TI  - [Cloning and analysis of phage Fab antibodies of mouse male specific antigen].
AB  - To clone mouse phage antibodies against H-Y antigen from a phage antibody
      library, three cycles of affinity enrichment of the mouse phage antibody library
      with male spleen cells and two cycles of nonspecific absorption with female
      spleen cells were performed. The presence of mouse Fab on the phage surface was
      determined by ELISA and sequence analysis. 9 of 15 strains can bind to male
      spleen cells with the specific activity. Recombination rate of the phage antibody
      library clones is 60%. Sequence analysis of the PCR products of plasmid DNA of E5
      clones show VH and Vkappa had common characteristics shared by other known
      variable region of antibodies. The mouse phage Fab antibody could be used for
      identifying H-Y antigen, and for the development of sex determination of early
      embryos in mammals.

PMID- 17037194
TI  - [Fusion expression of O type foot-and-mouth diseases virus VP1 gene and HSP70
      gene and induction of immune responses in mice].
AB  - Vp1 gene of O type foot-and-mouth diseases virus and M. tuberculosis HSP70 were
      expressed in methylotrophic yeast Pichia pastoris expression system. The results
      of cellular immune responses and humoral immune response were examined after
      BALB/c mice were immunized with fusion protein expressed in methylotrophic yeast
      Pichia pastoris. The genes was cloned into the vector pPICZalpha-A by routine
      molecular technique. The plasmid fusion (pPICZalphaA-vp1-HSP70) was created that
      HSP70 located downstream of VP1 gene of O type foot-and-mouth disease virus. Vp1
      was expressed by fusing to the amino terminus of M. tuberculosis hsp70 in yeast
      Pichia pastoris. The recombined fusion plasmid was transformed into
      methylotrophic yeast Pichia pastoris X-33 by electrophoration. The recombinant
      transformants were selected by Zeocin and induced by the addition of methanol
      every 24h. The expressived product analyzed by SDS-PAGE and Western blotting. The
      result indicated that the fusion protein(vp1-HSP70) has specific antigenicity.
      Mice were inoculated transcutaneous three times at a two-weeks interval with
      fusion protein, PBS and conventional inactivated vaccines. To evaluate the
      prophylaxtic efficacy of fusion protein, Titers of antibodies was detected by
      ELISA and proliferation of lymphocytes were determined by MTT. The results
      indicated that fusion protein could elicit specific humoral immune and cellular
      immune responses. Compared with conventional inactivated vaccines, fusion protein
      elicited slightly lower FMDV antibody level but stronger T cell proliferation.

PMID- 17037195
TI  - [Cloning, prokaryotic expression of chicken interferon-alpha gene and study on
      antiviral effect of recombinant chicken interferon-alpha].
AB  - The full length of chicken interferon alpha (ChIFN-alpha) gene was amplified by
      the polymerase chain reaction (PCR) from total liver genome of Sanhuang meat
      chicken and sequenced. The amplified gene was about 582bp. The coding region for
      mature protein (489bp) was subcloned into pET-28a(+). The recombinant plasmid pET
      28a(+)-IFNalpha was identified by enzyme digestion and DNA sequencing. Data of
      SDS-PAGE and Western-blot indicated that a 22kD fusion protein was expressed in
      the form of inclusion bodies with good immunity. The purity of inclusion bodies
      was above 70% and that of protein purified by nickel affinity chromatography was
      95%. The recombinant protein could inhibit H9N2 avian influenza virus (H9N2 AIV)
      replication on chick embryo fibroblast. 2 microg of recombinant IFN-alpha could
      completely protect Chick embryo from H9N2 AIV infection. The recombinant IFN
      alpha can also delay Newcastle disease virus (NDV) replication on chick embryo
      for 12 approximately 48h. Chicken administered recombinant IFN-alpha can resist
      the H9N2 AIV infection. The bioactivities of recombinant IFN-alpha purified by
      affinity chromatograph were 20 times higher than that of inclusion bodies.

PMID- 17037196
TI  - [Produce of marker-free transgenic tobacco plants by FLP/frt recombination
      system].
AB  - Selectable marker genes that usually encode antibiotic or herbicide resistances
      are widely used for the selection of the transgenic plants, but they become
      unnecessary and undesirable after transformation selection. An important strategy
      to improve the transgenic plants' biosafety is to eliminate the marker genes
      after successful selection. In the FLP/frt site-specific system of the 2 microm
      plasmid of Saccharomyces cerevisiae, the FLP enzyme efficiently catalyzes
      recombination between two directly repeated FLP recombination target (frt) sites,
      eliminating the sequence between them. By controlled expression of the FLP
      recombinase and specific allocation of the frt sites within transgenic
      constructs, the system can be applied to eliminate the marker genes after
      selection. Through a series of procedures, the plant FLP/frt site-specific
      recombination system was constructed, which included the frt containing vector
      pCAMBIA1300-betA-frt-als-frt and the FLP expression vector pCAMBIA1300-hsp-FLP
      hpt. The FLP recombinase gene was introduced into transgenic (betA-frt-als-frt)
      tobacco plants by re-transformation. In re-transgenic plants, after heat shock
      treatment, the marker gene als flanked by two identical orientation frt sites
      could be excised by the inducible expression of FLP recombinase under the control
      of hsp promoter. Excision of the als gene was found in 41% re-transgenic tobacco
      plants, which indicated that this systerm could make a great contribution to
      obtain the marker free transgenic plants.

PMID- 17037197
TI  - [Gene cloning and expression analysis of a male sterility related gene BoDHAR
      from broccoli].
AB  - A differentially expressed cDNA fragment obtained from a cDNA-AFLP analysis,
      which performed on floral buds of male sterile and fertile lines of cabbage, was
      used as a querying probe to blast the Genbank and Arabidopsis databases. Based on
      the assembled homologous cDNA sequences, a full-length cDNA of 633 bp for BoDHAR
      was cloned by RT-PCR. Furthermore, we have experimentally cloned and sequenced
      the 5' flanking sequence of gene BoDHAR by genomic walking method based on
      ligation-mediated PCR. The full length DNA sequence with 1486bp, containing two
      introns, was achieved. Homologous analysis shows that gene has 82.3% identity at
      nucleotide level, and 79.6% identity at amino acid level with Arabidopsis
      dehydroascorbate reductase (DHAR) gene AT1 G19570.1. Structurally, BoDHAR encodes
      a polypeptide of 210 amino acids, which contains a GST-c-DHAR domain highly
      conserved among other members of the DHAR superfamily and has multiple
      phosphorylation sites. Promoter predictions software indicated that the 5'
      upstream region contained putative transcription signals and conserved sequences,
      one CAAT-box, one G-box and four TGAC-like motifs. To advance our understanding
      of gene BoDHAR, tissue expression pattern were analyzed by semi-quantitative RT
      PCR. The results indicate that expression level of gene BoDHAR is higher in
      fertile buds than that in sterile buds, and expressed intensively in the anther.

PMID- 17037198
TI  - [Activation of silent antibiotic synthesis in Streptomyces lividans by disruption
      of a negative regulator nsdA, a gene conserved in Streptomyces].
AB  - The global regulatory gene, nsdA, negatively regulates antibiotics production in
      Streptomyces coelicolor. Southern blot experiment, using an nsdA fragment of S.
      coelicolor as probe, indicated that nsdA gene existed in many Streptomyces.
      Primers were designed based on the published sequences of S. coelicolor and S.
      avermitilis. PCR amplification and sequencing showed that nsdA in Streptomyces
      was conservative and that of S. lividans ZX64 has a 100% identity in the
      nucleotide sequence comparing with that of S. coelicolor A3 (2). The nsdA
      disrupted mutant of S. lividans was constructed named as WQ2. WQ2 was able to
      produce actinorhodin but the wild-type strain ZX64 did not, which has a silent
      gene cluster contributing to the biosynthesis of actinorhodin. However, the
      ability was lost when another copy of the wild nsdA gene was introduced into WQ2.
      All the results above indicate that nsdA homologous gene is wildly existent and
      conserved in Streptomyces. And it plays a role in negatively regulating the
      actinorhodin synthesis in S. lividans and disruption of it can activate the
      silent gene cluster.

PMID- 17037199
TI  - [The synthesis and function analysis of omega-3 fatty acid desaturase gene from
      Caenorhabditis briggssae].
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) have been broadly investigated and
      shown to exert many preventive and therapeutic actions besides their important
      role in maintenances human health and normal development. In mammals, the level
      of omega-3 PUFAs is relatively too low compared with omega-6 PUFAs, which
      metabolically and functionally distinct from omega-3 PUFAs and often have
      important opposing physiological functions. Either the inefficiency of omega-3
      PUFAs or the excess of omega-6 PUFAs will cause many healthy problems. So methods
      have been sought to increase the amount of omega-3 PUFAs and to improve the omega
      6/omega-3 ratio in body. In this study, the sFat-1 gene, which putatively encodes
      a omega-3 fatty acid desaturase, was chemically synthesized according to the
      sequence from Caenorhabditis briggssae (with codon usage modified), and
      constructed into a mammal expression vector pcDNA3. 1-sFat1-EGFP. This vector was
      introduced into CHO cells by lipid-mediated transfection, and it's expression
      quickly and effectively elevated the cellular omega-3 PUFAs (from 18-carbon to 22
      carbon) contents and dramatically improved the ratio of omega-6/omega-3 PUFAs.
      Cellular lipids extracts from stably selected cells were analyzed with GC-MS and
      the results showed that amount of total omega-6 PUFAs dropped from 48.97% (in GFP
      cells)to 35.29% (in sFat-1 cells), whereas the amount of total omega-3 PUFAs
      increased from 7.86% to 24.02%, respectively. The omega-6/omega-3 ratio also
      dropped from 6.23 to 1.47. These data demonstrates the Caenorhabditis briggssae
      omega-3 Fatty Acid Desaturase gene, sFat-1, was synthesized successfully and can
      produce omega-3 PUFAs by using the corresponding omega-6 PUFAs as substrates,
      which shows its potential for use in the production of omega-3 PUFAs in
      transgenic animals.

PMID- 17037200
TI  - [The effect of human IL-17F on growth of human hepatocarcinoma xenograft tumor in
      nude mice].
AB  - The human interleukin-17F(hIL-17F) gene was amplified by RT-PCR from PHA
      activated human peripheral blood mononuclear cells (PBMCs). It was then subcloned
      into the retrovirus vector pSIV-1. The pSIV-1/hIL-17F together with its two
      helper virus vectors pHIT456 and pHIT60 cotransfected into the package cell 293T
      by lipofectin to produce mature recombinant retrovirus, which was then used to
      infect SMMC-7721 hepatocarcinoma cells (HCCs), and the cells were selected in the
      presence of G418. The integration, transcription, expression of hIL-17F gene in
      SMMC-7721 cells was identified by PCR, RT-PCR and Western blot respectively. MTT
      and FCM showed that hIL-17F couldn't alter the proliferation and cell cycle of
      SMMC-7721 cells, but ELISA showed that it could down-regulate IL-6, IL-8 and VEGF
      expression. The effect of rhIL-17F supernatant on growth suppressing of ECV304
      cells was observed by MTT. The experiment of human hepatocarcinoma xenograft
      tumor in nude mice showed that the formation and growth rates of hIL-17F
      transgenic SMMC-7721 showed an obvious decline, and VEGF and CD34 expression and
      angiogenesis of the transgenic neoplasms was also evidently defined. hIL-17F can
      markedly inhibit the growth of human hepatocarcinoma xenograft tumor in nude mice
      by antiangiogenesis. This study provided an experimental evidence for further
      conducting tumor gene therapy by targeting vascularity and exploiting
      antiangiogenic novel medicine related to hIL-17F.

PMID- 17037201
TI  - [Gene construction, expression and activities analysis of human leptin].
AB  - Six 89bp primers were designed on the base of the cDNA sequence encoding the
      human leptin reported on the NCBI. The synthetic gene with 464bp encoding rhLep
      was obtained by SOE ( splicing by overlap extension) PCR. The expression vector
      pET22b(+)/rhLep was constructed and transformed into E. coli BL21 (DE3). The
      rhLep protein was expressed as inclusion bodies with the yield of more than 50%
      of total bacterial proteins after IPTG induction. The rhLep protein, which has a
      molecular weight about 16kD, was purified by Ni2+ affinity chromatography column
      and identified by SDS-PAGE. The MTT Assay shows that rhLep promotes EC304 cells
      growth at the low concentration of 10ng/mL to 30 ng/mL, and rhLep appears
      cytotoxic to EC304 cells with the high dose of 50ng/mL to 225ng/mL. The viability
      of EC304 cells decreases to 1.2% with the concentration of 225ng/mL of rhLep. The
      massive apoptosis of rhLep on EC304 cells is observed by AO-staining under
      fluorescent microscope. All these results would lay the foundation for the
      further study of its biological functions in vitro and in vivo.

PMID- 17037202
TI  - [Transgenic mice produced by intracytoplasmic sperm injection].
AB  - In our previous study, normal and fertile mice were successful produced from
      oocytes following intracytoplasmic sperm injection (ICSI). In the present study,
      the possibility of producing transgenic embryos and offspring with this procedure
      was evaluated. After freezing-thawed once using HEPES-CZB medium without
      cryoprotectants, the cauda sperm from KM fertile male were exposed to the
      circular or linear pEGFP-N1 DNA for 1 min and then co-injected into metaphase II
      oocytes of B6D2F1 strain. When the zygotes with two pronuclei were cultured in
      CZB medium to day 3.5, 39.1% (9/23) of them, derived from oocytes co-injected
      with sperm head and pEGFP-N1 plasmid DNA, were expressed GFP protein. After
      transfer of the ICSI embryos with two pronuclei from co-injection of sperm head
      and foreign DNA, seven recipients delivered 30 pups (23.8%, 30/126). Southern
      blot results revealed that three of sixteen offspring integrated with GFP and
      neomycin genes together (18.8 %). Interestingly, all of them were produced from
      oocytes co-injected sperm head and linear DNA (33.3%, 3/9), while none of seven
      ICSI offspring integrated either GFP or neomycin gene in the group of co
      injection of sperm head and circular plasmid DNA. These results indicated that
      the high efficiency of transgenic mouse could be produced by ICSI. It may be
      shown that linear DNA is more easily to integrate into host genome than circular
      DNA when ICSI was used to produce transgenic animals.

PMID- 17037203
TI  - [Rapid detection of Pseudomonas aeruginosa by the fluorescence quantitative PCR
      assay targeting 16S rDNA].
AB  - The 16S rDNA specific primers were designed for rapid detection of Pseudomonas
      aeruginosa (PA) by the fluorescence quantitative PCR (FQ-PCR) assay, based upon
      multiple sequence alignment and phylogenetic tree analysis of the 16S rDNAs of
      over 20 bacteria. After extraction of PA genomic DNA, the target 16S rDNA
      fragment was amplified by PCR with specific primers, and used to construct
      recombinant pMDT-Pfr plasmid, the dilution gradients of which were subjected to
      the standard quantitation curve in FQ-PCR assay. Different concentrations of PA
      genomic DNA were detected by FQ-PCR in a 20microL of reaction system with SYBR
      Green I. At the same time, various genomic DNAs of Staphylococcus aureus,
      Salmonella typhi, Shigella flexneri, Proteus vulgaris, Staphylococcus
      epidermidis, Escherichia coli, and Mycobacterium tuberculosis were used as
      negative controls to confirm specificity of the FQ-PCR detection assay. Results
      demonstrated that the predicted amplified product of designed primers was of high
      homology only with PA 16S rDNA, and that sensitivity of the FQ-PCR assay was of
      3.6pg/microL of bacterial DNA or (2.1 x 10(3) +/- 3.1 x 10(2)) copies/microL of
      16S rDNA, accompanied with high specificity, and that the whole detection process
      including DNA extraction could be completed in about two hours. In contrast to
      traditional culture method, the FQ-PCR assay targeting 16S rDNA gene can be used
      to detect PA rapidly, which exhibits perfect application prospect in future.

PMID- 17037204
TI  - [Preparation of new lipid-hydroxyapatite-DNA complex and gene transfection
      reseach in eukaryotic cell].
AB  - This work was directed at obtaining a better gene carrier to improve the effects
      of gene delivery. Neutral liposomes made from cholesterol, lecithin and DOPE by
      reverse evaporation technique were used for encapsulating DNA-HAP complex which
      was made from DNA and optimized HAP. The sizes of complexes and the efficiency of
      encapsulation were detected. The efficiency of transfection into Hela cells was
      shown by observation of X-gal staining and measurement of transfection
      efficience. The average size of complexes was 643nm, the average encapsulating
      efficiency of DNA in microspheres reached 11.67%. These Lipid-Hydroxyapatite-DNA
      complex (LHD) could be transfected into mammalian cells. The Lipid-Hydroxyapatite
      DNA complex prepared by reverse evaporation technique could be applied availably
      in DNA delivery system, and it gave another thinking to increase the gene
      transfection of non- viral genetic vector.

PMID- 17037205
TI  - [Production of gastrodin through biotransformation of p-hydroxybenzaldehyde by
      cell suspension cultures of Datura tatula L].
AB  - The conversion of exogenous p-hydroxybenzaldehyde to p-hydroxy-methyl-phenol-beta
      D-glucoside (gastrodin) was studied by using cell suspension culture of Datura
      tatula L. The chemical structure of this synthesized gastrodin was identified
      based on the spectral analysis and chemical evidence. The conversion procedure of
      p-hydroxybenzaldehyde into gastrodin by D. tatula L. cell suspension cultures was
      established. The synthesized gastrodin (II) was isolated from the ferment liquor
      and identified by spectral analysis. At the same time, the p-hydroxybenzyl
      alcohol (I) converted through biotransformation of p-hydroxybenzaldehyde by cell
      suspension cultures of D. tatula L. was also isolated and identified. The
      efficiency of glucosylation of p-hydroxybenzaldehyde was remarkably enhanced by
      adding salicylic acid (0.1 mg/L) and keeping the lower pressure (0.001MPa) in 25L
      airlift loop bioreactor. The biotransformation of exogenous p-hydroxybenzaldehyde
      to gastrodin by cell suspension culture of D. tatula L. is a promising approach.

PMID- 17037206
TI  - [Effect of homogeneity on cell growth and anthocyanin biosynthesis in suspension
      cultures of Vitis vinifera].
AB  - The instability of secondary metabolite production is a ubiquitous problem in
      plant cell culture. To understand the instability, the investigation of
      anthocyanin accumulation in suspension cultures of Vitis vinifera, as a model
      system, has been initiated in our laboratory. Suspension culture of a relatively
      homogeneous cell line E of V. vinifera, was established by long-term cell line
      selection by anthocyanin content differentiation. The aggregate size of E was
      smaller than that of other cell lines obtained by routine screening method. The
      variation coefficients of anthocyanin content in suspension cultures of E were
      8.7% in long-term subcultures and 5% in repeated flasks, respectively. The
      effects of elicitor, precursor feeding and light irridiation on biomass and
      anthocyanin accumulation in suspension cultures of E had been investigated and
      the results showed that all the variation coefficients were lower than 12% and
      this indicated the importance of homogeneity on stable production in plant cell
      culture. With the combination treatment of 30micromol/L phenylalanine and
      218micromol/L methyl jasmonate in the dark in suspension cultures of E, the
      anthocyanin content and production in suspension culture of E was 5.89-fold and
      4.30-fold of the controls, respectively, and all the variation coefficients of
      biomass and anthocyanin accumulation were lower than those of the controls in 5
      successive subcultures.

PMID- 17037207
TI  - [Refolding of the fusion protein of recombinant enterokinase light chain rEKL].
AB  - The fusion protein of enterokinase light chain, DsbA-rEKL, was expressed mainly
      in inclusion body in E. coli. The recombinant bacteria was fermented to high
      density, with high expression of the fusion protein. After being washed with 0.5%
      Triton X-100 and 4mol/L urea, the inclusion body was dissolved in 6mol/L
      guanidine and 100mmol/L DTP, derivatized by cystine and refolded by pulse
      refolding. The strategy of pulse refolding involved the addition of 0.03mg/mL of
      fusion protein until its final concentration reached 0.3mg/mL. The refolded
      protein was autocleaved and the active EKL molecule was released after adding
      2mmol/L CaCl2. Using the two-step purification processes of IDA-Sepharose
      chromatography and Q-Sepharose chromatography, the purity of rEKL was found to be
      above 95%, with a high activity to cleave the recombinant reteplase fusion
      protein Trx-rPA. The yield of purified rEKL was more than 60mg/L of cultures. As
      a result, the therapeutic proteins like rPA could be produced on a large-scale in
      a way such as expressed in the form of fusion proteins.

PMID- 17037208
TI  - [Continuous ethanol fermentation coupled with recycling of yeast flocs].
AB  - A continuous ethanol fermentation system composed of three-stage tanks in series
      coupled with two sedimentation tanks was established. A self-flocculating yeast
      strain developed by protoplast fusion from Saccharomyces cerevisiae and
      Schizosaccharomyces pombe was applied. Two-stage enzymatic hydrolysate of corn
      powder containing 220g/L of reducing sugar, supplemented with 1.5g/L (NH4)2HPO4
      and 2.5g/L KH2PO4, was used as the ethanol fermentation substrate and fed into
      the first fermentor at the dilution rate of 0.057h(-1). The yeast flocs separated
      by sedimentation were recycled into the first fermentor as two different models:
      activation-recycle and direct recycle. The quasi-steady states were obtained for
      both operation models after the fermentation systems experienced short periods of
      transitions. Activation process helped enhance the performance of ethanol
      fermentation at the high dilution rates. The broth containing more than 101g/L
      ethanol, 3.2g/L residual reducing sugar and 7.7g/L residual total sugar was
      produced. The ethanol productivity was calculated to be 5.77g/(L x h), which
      increased by more than 70% compared with that achieved in the same tank in series
      system without recycling of yeast cells.

PMID- 17037209
TI  - [Model study on CO2 removal by photobioreactor].
AB  - The key point of study on CO2 removal by microalgae cultured in a photobioreactor
      is to improve CO2 removal capability. In this paper, a model of air-lift
      photobioreactor was developed by combination of conditions including the velocity
      of flow, the degree of mixing, the gas-liquid mass transfer and the rate of
      photosynthesis, and two corresponding simplified methods, such as time
      discretization and lumped parameters were put forward. Using a method of lumped
      parameters, the model for simulation of time course of DO, pH in the column air
      lift photobioreactor and prediction of CO2, O2 concentrations in the outlet gas
      under different CO2 concentration in the aeration gas was thoroughly discussed.
      Experimental data were also used to verify the model which could potentially be
      applied to rational design of the photobioreactor, high-density culture of
      microalgae and efficient removal of CO2.

PMID- 17037210
TI  - [The preparation of an elicitor from a fungal endophyte to enhance artemisinin
      production in hairy root cultures of Artemisia annua L].
AB  - The different components of crude mycelium of the predominant endophytic
      Colletotrichum gloeosporioides of Artemisa annua have been extracted by the
      methods of acid hydrolysate. We compared the effect of the isolated components on
      artemisin biosynthesis in hairy root cultures. Therefore, the oligosaccharide
      elicitor from C. gloeosporioides has been partially purified by column
      chromatography of Sephadex G25. The isolated oligosaccharide B II (elicitor, MW <
      2500) has been revealed to promote the production of artemisinin in Artemisia
      annua hairy root cultures. When hairy roots of 23-day old cultures (later growth
      phase) were exposed to the elicitor at 0.4 mg/mL for 4 days, the maximum
      production of artemisinin reached to 13.51 mg/L, a 51.63% increase over the
      control. This is the first report on the stimulation of artemisinin production in
      hairy roots by the oligosaccharide elicitor from an endophytic fungus of A.
      annua.

PMID- 17037211
TI  - [Isolation and characterization of gamma-TMT gene promoter from Arabidopsis
      thaliana].
AB  - Vitamin E (Tocopherols) is lipid-soluble antioxidants and essential for human
      health. Gamma-tocopherol methyltransferase (delta-TMT), one of the key enzymes in
      tocopherol biosynthetic pathway in plants, converts delta,sigma-tocopherols into
      alpha,beta-tocopherols. In this study, we isolated the 1552 bp promoter of
      Arabidopsis TMT gene. The promoter was fused with GUS reporter gene and this
      expression cassette was introduced into wild Arabidopsis thaliana by
      Agrobacterium-mediated transformation. GUS staining shows that GUS gene is
      expressed in leaves, stems and flowers, with the highest expression in young
      leaves, stamens and stem apices, while not observable in roots, seeds and
      siliques. The data indicate that gamma-TMT gene promoter is likely to be
      expressed preferentially in some of the tissues of Arabidopsis.

PMID- 17037212
TI  - [Process performance of simultaneous anaerobic sulfide and nitrate removal].
AB  - The process performance of simultaneous anaerobic sulfide and nitrate removal was
      studied. The results showed that the process held a high sulfide and nitrate
      removal loading rate of 3.73kg/(m3 x d) and 0.80kg/(m3 x d), respectively, under
      steady state. It was capable of tolerating high influent substrate concentration
      (580mg/L and 110mg/L) with the optimum substrate concentration of 280mg/L and
      67.5mg/L. It was capable of tolerating short hydraulic retention time (HRT) with
      the optimum HRT of 0.13d. Careful operation was needed when HRT was shortened
      because the process performance was deteriorated abruptly.

PMID- 17037213
TI  - [Study on vitrification of porcine embryos by open pulled straw method].
AB  - 291 embryos (Blastocyst/Morula) from 20 donor sows were vitrified by two step
      method with OPS (open pulled straw) in solution I (TCM199 + 20% FBS + 10% EG +
      10% DMSO) for 3min, and solution II (TCM199 + 20% FBS + 20% EG + 20% DMSO +
      0.4mol/L SUC) for 1min, stored in liquid nitrogen for 3 months, and transferred
      into 8 recipient sows after warming, one recipient sow was pregnant and 8 alive
      piglets were born. This is the first paper to report getting alive piglets by
      vitrification in China.

PMID- 17037214
TI  - [Effects of resveratrol on pig primary preadipocytes proliferation,
      differentiation and transcription expression of Sirt1 gene].
AB  - 1 approximately 3 days old Piglet's primary preadipocytes in vitro were cultured
      and treated with 0micromol/L (control group), 10microlmol/L (lower dose group),
      20micromol/L(middle dose group) and 50micromol/L, 100micromol/L (higher dose
      group) RES. Cell proliferation and viability were analyzed by MTT assay. The
      degree of differentiation and adipogenesis were measured by Oil Red O staining
      extraction assay and the expression of Sirt1 (sirtuin) mRNA were detected by RT
      PCR. The results showed the optical density (OD) of MTT and Oil Red O staining
      were all decreased, especially treated by 50micromol/L, 100micromol/L RES at 72h
      and 96h (P < 0.01); the ratio of OD of the expression of Sirt1 mRNA to that of
      beta-actin mRNA were increased after treated by 100micromol/L RES (P < 0.01). RES
      can inhibit proliferation and differentiation of pig preadipocytes in certain
      degree. Higher dose of RES can markedly decrease adipogenesis and prevent
      preadipocytes differentiation into adipocytes, which may be in part associated
      with its effect on increasing the expression of Sirt1 mRNA.

PMID- 17037215
TI  - [Application of optical proteinchip in detecting phage M13KO7].
AB  - Avidin layer was bound on the substrate surface of Silicon wafer modified with
      aldehyde. The interaction between avidin and biotin was adopted for the
      immobilization of mouse monoclonal biotin-anti-M13 (antibody GP3)-labeled biotin.
      The surface was incubated in a solution containing phage M13KO7, which was
      trapped by the antibody GP3 with the interaction between phage M13KO7 and
      antibody GP3, resulting in a variation of layer thickness that was detected by
      imaging ellipsometry. The results showed a saturated layer of antibody GP3 with a
      thickness about 6.9 nm on the surface of the silicon wafer. The specific
      interaction between phage M13KO7 and antibody GP3 resulted in a variation of the
      layer thickness. The layer of phage M13KO7 bound with antibody GP3 was 17.5 nm in
      the concentration of 1.1 x 10(10) pfu/mL. Each variation of layer thickness
      corresponded to a concentration of phage M13KO7 in the range of 0.1 x 10(10)
      approximately 2.5 x 10(10) pfu/mL, with the sensitivity of 10(9) pfu/mL. Compared
      with other methods, the optical protein-chip requires only short measurement
      time, is label free, is a quantitative test, and can be visualized. This study
      could be significant on the investigation of interactions between the antibody
      and virus, and shows potential in the early diagnosis of virosis.

PMID- 17037216
TI  - [The advancement of AFLP technology].
AB  - AFLP technology has been widely used in molecular biology due to its integration
      of several advantages of high throughput, high efficiency and requiring no
      sequence information, etc. Great changes have been achieved in recent years in
      AFLP-related technologies and platforms. There are several AFLP-expanded
      technologies available. These improved technologies are capable of distinguishing
      the heterozygote from the homozygote and of converting any AFLP band of interest,
      without much effort, into locus-specific markers, which can be deployed for
      massive locus detection and for gene isolation. This review focuses on these
      favorable changes from conventional AFLP technology into more effective and more
      practicable AFLP-related ones. Understanding these advancements and AFLP-expanded
      technologies will facilitate the achievement of our research goals.

PMID- 17037217
TI  - Infant feeding in Saudi Arabia: mothers' attitudes and practices.
AB  - We conducted a nationwide cross-sectional survey of 4872 mothers (mostly Saudi)
      to study infant feeding patterns. Information was collected about their feeding
      practices with their youngest child using pre-tested questionnaires. About four
      fifths of the mothers had received health education about breastfeeding, most
      often from medical staff; younger mothers tended to be better informed.
      Approximately 92% fed colostrum to the newborn, but 76.1% had introduced bottle
      feeding by 3 months (48.3% cited insufficient milk as the reason for introducing
      the bottle). This was significantly related to nationality and education level.
      Mixed feeding (breastfeeding and bottle-feeding) was popular. Solid foods tended
      to be introduced late and this was significantly related to nationality, age and
      education level.

PMID- 17037218
TI  - Epidemiological study of measles in Ghazvin, Islamic Republic of Iran, April 1997
      April 2003.
AB  - We studied measles incidence and morbidity in Ghazvin district by retrospective
      review of cases registered at the central health office and admitted to two
      hospital in Ghazvin city during April 1997-April 2003. There were 824 clinically
      confirmed cases of measles over the 6-year period giving a mean annual incidence
      of 18.67 per 100 000 population, higher than for the country generally. There
      were no deaths from measles. Of the 824 cases, 591 (71.1%) had serum specimens
      for serological analysis and 199 (24.3%) were confirmed serologically. Of the
      serologically confirmed cases, the greatest proportion (44.2%) were over 20 years
      (median age was 17.5 years), 54.5% had been in contact with a measles case and
      21.6% cases had received 2 doses of vaccine. We studied 33 serologically
      confirmed hospitalized cases. Common complications were vomiting (45.5%),
      diarrhoea (42.4%) and pneumonia (21.2%). The mean duration of hospitalization was
      3.8 days.

PMID- 17037219
TI  - Evaluation of child deaths registration in a Jordanian community.
AB  - A retrospective population-based household survey was conducted in Deir-Alla
      district during July-August 2002. The aim was to determine the extent of under
      registration of child deaths and stillbirths, estimate infant mortality and under
      5 mortality rates and identify factors affecting under-registration. We
      interviewed 1024 women aged 15-49 years about deaths in the last 3 children born.
      A modified version of the preceding birth mortality questionnaire was used. We
      found 72.2% of child deaths, including all 45 stillbirths, were unregistered.
      Under-registration was significantly related to child's age at death, stillbirths
      and dead infants < 1 year being more likely to be unregistered. The officially
      published infant mortality rate is not a credible indicator of infant deaths.

PMID- 17037220
TI  - Knowledge, attitudes and practices of secondary-school pupils in Oman: I. health
      compromising behaviours.
AB  - We investigated the practice of some of health-compromising behaviours among
      Omani adolescents and their correlates in a nationally representative secondary
      school-based sample of 1670 boys and 1675 girls. The mean age of the sample was
      17.13 (SD 1.35) years. Through a self-administrated questionnaire the adolescents
      were asked about 6 risky behaviours: current smoking, ever use of alcohol,
      succumbing to peer pressure to take illicit drugs, driving without a licence,
      speeding while driving and being involved in a physical fight in the month prior
      to the survey. Demographic and psychosocial variables related to their risk
      behaviours were also assessed. The results indicated that 4.6 % were current
      smokers, 4.3% had drunk alcohol and 4.6% had taken drugs. About 20% had been
      involved in a physical fight in the month prior to the survey, 33.4% drove
      without a licence and 33.9% liked to speed. Male sex and low self-esteem were the
      strongest predictors of risky behaviour.

PMID- 17037221
TI  - Knowledge, attitudes and practices of secondary-school pupils in Oman: II.
      reproductive health.
AB  - We examined the knowledge, attitudes and practices of Omani adolescents with
      regard to reproductive health in a nationally representative secondary school
      based sample of 1670 boys and 1675 girls. Through a self-administrated
      questionnaire the adolescents were asked about puberty, marriage, birth spacing
      and AIDS and sexually transmitted infections. Only half of the sample knew the
      changes at puberty of their own sex, while even fewer knew the changes in the
      opposite sex. Girls were inclined significantly towards later age of marriage
      than boys. The mean number of children desired by the sample was 4.9. About two
      thirds of the adolescents had a positive attitude toward modern contraceptive
      methods and intended to use them in the future. Knowledge of fertility period was
      poor as was knowledge of AIDS and sexually transmitted infections. There was a
      high rate of approval (80%) of female genital cutting by both sexes.

PMID- 17037222
TI  - Depression in adolescents: gender differences in Oman and Egypt.
AB  - To investigate the differences between adolescent boys and girls, the rates of
      depression and associated factors were determined for secondary school
      adolescents in 2 different samples, 552 in South Sharqiya, Oman, and 1577 in
      Alexandria, Egypt. Multivariate logistic regression models were used to
      investigate the correlates of depression. In Alexandria, the rate of having
      depressive symptoms in girls was almost double that in boys. In Oman, however,
      there was no significant difference. History of abuse during adolescence
      predicted depression in almost all the models. Poor relationship with parents
      affected girls more than boys in Alexandria and in the merged sample. Gender
      differences in rates or correlates of depression exist but may differ for
      different countries.

PMID- 17037223
TI  - Post-traumatic stress disorder in children witnessing a public hanging in the
      Islamic Republic of Iran.
AB  - A study was made of post-traumatic stress disorder in 200 children aged 7-11
      years who had witnessed a public hanging next to their school in Isfahan, Islamic
      Republic of Iran. A standard checklist was completed through interviews with the
      children's parents 3 months after the event. Post-traumatic stress disorder
      symptoms were identified in 104 children (52%), with 88 suffering re-experiences,
      24 avoidance and 62 hyperarousal. The mean stress severity according to the Child
      Post-Traumatic Stress Reaction Index was 39.1, indicating a moderate to severe
      severity of stress. The study highlights the serious emotional effects on
      children who witness traumatic events.

PMID- 17037224
TI  - Pattern of motorcycle-related injuries in Tehran, 1999 to 2000: a study in 6
      hospitals.
AB  - We studied motorcycle-related injuries in Tehran from 23 August 1999 to 21
      September 2000 in 6 hospitals. Data were obtained from the trauma registry and
      questionnaires completed by trained physicians. Of a total of 8500 patients with
      trauma injuries, 1332 were motorcyclists, with a male to female ratio of 15:1. Of
      these, 1226 patients were driving the motorcycle at the time of the accident and
      75 were pillion passengers. Crashes involving another vehicle were the commonest
      kind of accident (72.5%). Helmet use was noted in only 8.6% of cases. There were
      28 fatalities and head injuries were the prominent cause of death. Of those who
      died, none had been wearing a helmet at time of the crash. Only 2.7% of helmeted
      riders sustained a head injury, compared with 11.2% of riders without a helmet.
      The commonest musculoskeletal injury was fracture: tibial fracture with 509 cases
      (49.8%) comprised the largest proportion.

PMID- 17037225
TI  - Predictors of cardiovascular risk factors in Tehranian adults: diet and
      lifestyle.
AB  - We carried out a dietary intake assessment in 486 adults 20 from the Tehran Lipid
      and Glucose Study. There was a strong positive association between body mass
      index (BMI) and serum triglycerides (beta = 1.6, P < 0.05) and carbohydrate
      intake and triglycerides (beta = 2.4, P < 0.05). There was also an association
      between low-density lipoprotein cholesterol and weight (beta = 1.1, P < 0.05),
      age (beta = 1.6, P < 0.05) and cholesterol intake (beta = 0.7, P < 0.01). For 1
      unit increase in either BMI, waist to hip ratio or saturated fatty acid intake,
      diastolic blood pressure increased 0.6, 0.9 and 0.1 mmHg, respectively (P <
      0.05). Dietary and non-dietary factors have an association with, and play a role
      as predictors of, CVD risk factors.

PMID- 17037226
TI  - [Quality of ambulatory care of non-insulin dependent diabetic patients].
AB  - We assessed the quality of care provided to non-insulin treated diabetic patients
      by examining the medical records of 248 such patients attending our outpatient
      department in 2002. The mean age was 59.5 (SD 10.1) years, 62.1% were women and
      known duration of diabetes was 8.6 (SD 5.9) years. The majority of patients were
      treated with a combination of sulfonylurea and metformin. Glycaemic control was
      assessed using fasting blood glucose in 96.8% of patients, post-prandial blood
      glucose in 31.9% and glycated haemoglobin in 52.4%. Weight was measured at least
      once for 88.7% of patients, blood pressure for 91.1% of patients and lipid levels
      for 64.9%. Body mass index was less than 25 kg/m2 in 12.3% of patients and blood
      pressure less than 140/90 mmHg in 40.3%. Foot examination was noted in only 2% of
      records, electrocardiography was performed for 25% of patients and fundoscopy for
      21%. Proteinuria was documented in 19.8% of patients and plasma urea and/or
      creatinine in 57.3%.

PMID- 17037227
TI  - Frequency of peptic ulcer disease during and after Ramadan in a United Arab
      Emirates hospital.
AB  - We aimed to study the effect of Ramadan fasting on the occurrence of peptic ulcer
      disease and its complications in patients presenting to the Accident and
      Emergency Department at Al-Ain hospital, United Arab Emirates (UAE). We
      retrospectively reviewed patient records over the 10-year period, 1992 to 2002.
      Of 470 patients treated for peptic ulcer disease, 215 were seen during Ramadan
      and 255 in the month after Ramadan. The frequency of peptic ulcer disease was
      higher after Ramadan than during Ramadan but this was not statistically
      significant. Peptic ulcer disease occurred more frequently in the age group 30-49
      years. Peptic ulcer perforation occurred more frequently after Ramadan but the
      difference was not significant. Regression analysis identified the following
      variables as predictors of peptic ulcer disease: anorexia, pain, hypertension,
      smoking, epigastric pain, diabetes and family history.

PMID- 17037228
TI  - Seroepidemiology of selected zoonotic infections in Basra region of Iraq.
AB  - A community-based seroepidemiological study was made of 4 common zoonotic
      infections (brucellosis, hydatidosis, toxoplasmosis and visceral leishmaniasis)
      in 3 areas (rural, urban and suburban semirural) in Basra governorate, southern
      Iraq. The prevalence of brucellosis was higher in the suburban semirural area
      (29.3%) than the rural and urban areas. The prevalence of hydatidosis (19.0%
      35.5%) and toxoplasmosis (41.1%-52.1%) were relatively high in all 3 areas. With
      respect to visceral leishmaniasis, low rates of infection were reported (0.2%
      1.9%). The study shows in general that the suburban semirural area is at highest
      risk of zoonotic infections compared with other areas. The results could form a
      rational basis for the planning of an integrated comprehensive approach for
      control of zoonotic infections in the areas surveyed.

PMID- 17037229
TI  - Prevalence of bovine and human brucellosis in western Algeria: comparison of
      screening tests.
AB  - A serological study was carried out in Tiaret province in western Algeria on 1032
      cows distributed in 95 flocks to estimate the prevalence of Brucella infection
      and to compare the sensitivity and specificity of a range of agglutination tests.
      Screening tests showed 31.5% of herds positive using the buffered plate antigen
      test and 26.3% using the rose Bengal test compared with 15.7% with the complement
      fixation test. Using the complement fixation test as the gold standard for
      confirmatory tests, the Rivanol test was found to be more sensitive but less
      specific than tube agglutination in detecting brucellosis infection. Three
      isolates were identified from 105 blood samples from humans with brucellosis and
      50 samples of milk and tissues from infected cows and they were all Brucella
      melitensis biovar 3.

PMID- 17037230
TI  - [Cleaning and molluscicide treatment for schistosomiasis control].
AB  - We evaluated the effect of niclosamide treatment and the additional cleaning of
      basins and pools on the density and infection rate of Bulinus truncatus within
      the irrigation network of Oudaya. The period prior to molluscicide treatment
      (January-May) revealed a mean density of 151 snails/m2 in 1995-96 and 127
      snails/m2 in 1997-98. After cleaning had started, the mean density prior to
      molluscicide treatment fell to 84 snails/m2 in 1999-2000. After molluscicide
      treatment, densities dropped to very low levels only rising again from October.
      In November 1999-96 mean density reached 150 snails/m2 but after cleaning started
      in 1997-98 this only reached 80 snails/m2; in 1999-2000, when cleaning was
      undertaken 3 months before and after molluscicide treatment, it reached only 18
      snails/m2. From 1995 to 1996, the infection rate rose slightly (4.54% to 5.44%),
      but, from 1997, there was a significant drop (3.13% to 2.16%).

PMID- 17037231
TI  - Helminth eggs in raw and treated wastewater in the Islamic Republic of Iran.
AB  - To assess the type and load of helminths in wastewater and the quality of
      treatment, we examined the raw and treated wastewater of 8 wastewater treatment
      plants (WTP) in Tehran and 2 in Isfahan for the presence of helminth eggs during
      2002-2003. Wastewater samples obtained from both inlet and effluent of each
      treatment plant were examined on several occasions using the modified Bailenger
      method. Untreated entry wastewater in Tehran WTPs contained a larger variety of
      helminth eggs than those of Isfahan, as well as higher total egg counts. The
      helminths identified in the influent of Tehran included Ascaris lumbricoides,
      hookworms, Enterobius vermicularis, Trichostrongylus spp., Taenia spp.,
      Hymenolepis nana and Dicrocoelium dendriticum, while in Isfahan only A.
      lumbricoides, Trichostriogylus and H. nana were isolated. After treatment, the
      number of eggs/L fell to < or = 1 egg/L.

PMID- 17037232
TI  - Housing conditions and health in Jalazone Refugee Camp in Palestine.
AB  - We investigated some of the housing conditions at Jalazone Refugee Camp and their
      impact on refugees' health inside the camp, especially those with respiratory
      symptoms and diseases. A randomized sample of 200 housing units, representing one
      fifth of the camp's population, was selected. Approximately half of the people in
      our sample were under 15 years. Overcrowding and high population density were
      significant. There was a statistically significant relationship between some
      respiratory conditions (common cold, cough, tonsillitis and ear infection) and
      poor housing conditions (including damp and mould), overcrowding and high
      population density. A radical solution for the housing problem is needed to avert
      further negative health impacts.

PMID- 17037233
TI  - Dentists' perceptions of occupational hazards and preventive measures in East
      Jerusalem.
AB  - Dentists, like other health professionals, are exposed to various occupational
      health problems, with specific ones of their own. A randomly distributed sample
      of 40 (42.2%) dentists working in East Jerusalem was interviewed. A questionnaire
      was used to detect their perception of occupational hazards. Most respondents
      were aware of biological hazards: 38% specifically mentioned hepatitis B virus
      and 13% human immunodeficiency virus. Perceived sources of stress included
      factors that coincided with international data, such as relationships with
      patients, physical strain and economic pressure, but also some specific to the
      Palestinian culture such as relationships with other dentists and Israeli
      occupation tax policy when dealing with the Arab dentists in East Jerusalem.
      Chemical dependency was not mentioned as a potential hazard.

PMID- 17037234
TI  - Audit of prescribing practices of topical corticosteroids in outpatient
      dermatology clinics in north Palestine.
AB  - To analyse the prescribing pattern of topical corticosteroids, 802 outpatient
      dermatology prescriptions were randomly collected during June 2003-September 2003
      from all the 12 nongovernmental dermatological clinics in north Palestine. Of the
      2458 medications prescribed, 616 were topical corticosteroids. In most
      prescriptions, information about strength, duration of treatment and quantity to
      be used was inadequate, while information regarding frequency, route and area of
      application was adequate. High efficacy and highest efficacy corticosteroids were
      prescribed for approximately 18% of patients; intermediate efficacy preparations
      were prescribed for approximately 50%.

PMID- 17037235
TI  - National Register for the Blind: a tool for health programme management.
AB  - We carried out a retrospective analytical study of 3525 bilaterally blind people
      registered in Oman to the end of 2000. We described the examination method,
      maintenance of the register and analysis of data. Lists of different categories
      of blind people were distributed to various organizations for management and
      rehabilitation purposes. The role of the national register in addressing blinding
      cataract, corneal blindness, eradication of congenital rubella syndrome and care
      of blind people in Oman was also examined. The register was useful in identifying
      candidates for rehabilitation and also for monitoring regional efforts to manage
      curable blindness. This multiple use of the register could make it an important
      tool for health programme management in Oman.

PMID- 17037236
TI  - Serum endostatin and vascular endothelial growth factor levels in patients with
      pre-eclampsia.
AB  - We evaluated the prognostic value of serum endostatin and vascular endothelial
      growth factor (VEGF) for diagnosis of pre-eclampsia. We determined VEGF and
      endostatin levels in the sera of 20 healthy, non-pregnant women and 64 pregnant
      women: 20 healthy, 20 with mild pre-eclampsia and 24 with severe pre-eclampsia.
      Serum levels of these factors in non-pregnant women were similar to those in
      healthy pregnant women. However, serum levels were significantly higher with mild
      or severe pre-eclampsia compared with normal pregnancies and significantly higher
      with severe rather than with mild pre-eclampsia. Elevated levels significantly
      increased risk more than severity of pre-eclampsia. VEGF and endostatin could be
      used to differentiate between pre-eclamptic and normal pregnancies and to
      discriminate mild pre-eclampsia from severe pre-eclampsia.

PMID- 17037237
TI  - Effect of menopause and renal function on vitamin D status in Iranian women.
AB  - The effects of menopause and renal function on serum parameters of the vitamin D
      endocrine system were studied in a cross-sectional sample of 676 healthy women
      aged 20-74 years in Shiraz. Low serum 25-hydroxyvitamin D (25-OHD) was found in
      52.9% of the women. Serum parathyroid hormone (PTH) increased significantly over
      the age span in premenopausal women (r= 0.13, P= 0.02). In premenopausal and
      postmenopausal women, serum levels of 25-OHD, phosphorus and calcium were stable
      across the age span. There was no significant correlation between creatinine
      clearance or serum PTH (r= -0.016, P= 0.66) and 25-OHD (r= 0.012, P= 0.74). The
      high prevalence of vitamin D deficiency warrants consideration of dietary
      supplementation.

PMID- 17037238
TI  - Monte Carlo simulation on the effect of different approaches to thalassaemia on
      gene frequency.
AB  - We used computer simulation to determine variation in gene, heterozygous and
      homozygous frequencies induced by 4 different approaches to thalassaemia. These
      were: supportive therapy only; treat homozygous patients with a hypothetical
      modality phenotypically only; abort all homozygous fetuses; and prevent marriage
      between gene carriers. Gene frequency becomes constant with the second or the
      fourth strategy, and falls over time with the first or the third strategy.
      Heterozygous frequency varies in parallel with gene frequency. Using the first
      strategy, homozygous frequency falls over time; with the second strategy it
      becomes constant; and with the third and fourth strategies it falls to zero after
      the first generation. No matter which strategy is used, the population gene
      frequency, in the worst case, will remain constant over time.

PMID- 17037239
TI  - Seroprevalence of hepatitis C virus specific antibodies among Iraqi children with
      thalassaemia.
AB  - The seroprevalence of hepatitis C virus (HCV) specific antibodies and HCV
      genotypes distribution were studied among 559 Iraqi children with thalassaemia in
      receipt of repeated blood transfusions. HCV-specific antibodies were detected in
      376 (67.3%) serum samples using third-generation enzyme immunoassay and
      confirmatory immunoblot assays. Of 78 randomly selected sera, 48 (61.5%) were HCV
      RNA positive. HCV genotypes 1a, 1b, 4 and mixed 1b and 4 were demonstrated in 13
      (27.1%), 11 (22.9%), 17 (35.4%) and 7 (14.6%) sera respectively. Strict measures
      for the controlling the spread of HCV are needed by introducing advanced
      techniques for blood donor screening.

PMID- 17037240
TI  - Flat foot among Saudi Arabian army recruits: prevalence and risk factors.
AB  - This study determined the prevalence and risk factors for flat foot among 18-21
      year-old male Saudi Arabian army recruits. Among 2100 military recruits, the
      prevalence of flat foot was 5.0%. A case-control logistic regression analysis of
      risk factors (104 cases and 412 controls) showed family history, wearing shoes
      during childhood, obesity and urban residence were significantly associated with
      flat foot. No associated complaints were reported among the cases and thus
      flexible flat foot does not seem to be a cause of any disability.

PMID- 17037241
TI  - [Patient archiving and communication systems: an example of the clinical
      application of information technology].
AB  - The applications of patient archiving and communication systems have increased
      lately, particularly since the medical imaging companies began to distribute the
      software along with machines. These systems are very important in developing
      clinical work, particularly in critical care, for example following cardiac
      surgery. This paper describes these systems and explores how they work, as an
      example of the application of information technology in developing clinical work,
      and critical care in particular.

PMID- 17037242
TI  - Critical care medicine in Saudi Arabia.
AB  - Critical care medicine remains underdeveloped in many parts of the world. In
      Saudi Arabia, there have been major developments in the past 2-3 decades. The
      purpose of this review is to give an account of the current status of critical
      care practice (including services provided during the haj season) and training in
      Saudi Arabia using examples of primary, secondary and tertiary care hospitals.
      The future needs of the profession are also addressed.

PMID- 17037243
TI  - Creatinine, blood urea nitrogen and thyroid hormone levels before and after
      haemodialysis.
AB  - A study was carried out on 57 patients with chronic renal failure in a hospital
      in Kerman city, Islamic Republic of Iran. Blood samples were taken before and
      after haemodialysis to measure blood urea nitrogen and serum creatinine,
      triiodothyronine (T3) and thyroxine (T4) levels. Findings revealed that before
      dialysis T4 in 11 cases and T3 in 29 cases were lower than the normal range, but
      after haemodialysis only 3 cases for T4 and 15 cases for T3 were lower than
      normal levels. The remaining cases reverted to normal state. We suggest that a
      feedback relationship exists between the major end catabolic products (creatinine
      and blood urea nitrogen) and thyroid hormone serum levels.

PMID- 17037244
TI  - Distribution of malocclusion types in 7-9-year-old Iranian children.
AB  - This study assessed the malocclusion types, very severe crowding and need for
      serial extraction among a random sample of 7-9-year-old children in Shiraz,
      Islamic Republic of Iran. Of the 3776 children 30.6% had normal occlusion, 47.4%
      class I malocclusion, 13.7% class II division 1 malocclusion (male/female ratio
      3:2), 1.0% class II division 2 malocclusion (male/female ratio 3:1) and 2.1%
      class III malocclusion. Among the children examined, 47.9% had crowding problems
      and 14.7% of them had class I malocclusion with very severe crowding-more girls
      (17.3%) than boys (12.1%). No correlation was observed between the types of
      malocclusion and family size, parents' occupation or level of education.

PMID- 17037245
TI  - Cryptococcus neoformans var. gattii meningitis in Egypt: a case report.

PMID- 17037246
TI  - Unusual association between renal tubular acidosis and Chilaiditi syndrome: a
      case report.

PMID- 17037247
TI  - Evaluating the community-oriented medical education in two medical schools in
      Sudan.

PMID- 17037248
TI  - [Avian influenza: a panic pandemia?].

PMID- 17037249
TI  - DNA fingerprinting by ERIC-PCR for comparing Listeria spp. strains isolated from
      different sources in San Luis, Argentina.
AB  - In this study, a total of 24 Listeria spp. strains were analyzed. Twenty-two
      isolates were obtained in San Luis (Argentina) from human, animal, and food
      samples. Two types of strains, Listeria monocytogenes CLIP 22762 and Listeria
      innocua CLIP 74915, were included as reference strains. All isolates were
      biochemically identified and characterized by serotyping, phage typing, and
      amplification of the flaA gene by polymerase chain reaction (PCR). Repetitive
      intergenic consensus (ERIC) sequence-based PCR was used to generate DNA
      fingerprints. On the basis of ERIC-PCR fingerprints, Listeria spp. strains were
      divided into three major clusters matching origin of isolation. ERIC-PCR
      fingerprints of human and animal isolates were different from those of food
      isolates. In addition, groups I and II included ten L. monocytogenes strains, and
      only one Listeria seeligeri strain. Group III included nine L. innocua strains
      and four L. monocytogenes strains. Computer evaluation of ERIC-PCR fingerprints
      allowed discrimination between the tested serotypes 1/2b, 4b, 6a, and 6b within
      each major cluster. The index of discrimination calculated was 0.94. This study
      suggests that the ERIC-PCR technique provides an alternative method for the
      identification of Listeria species and the discrimination of strains within one
      species.

PMID- 17037250
TI  - [Modified EMJH medium for cultivation of Leptospira interrogans serogroup
      ballum].
AB  - Strains within the Ballum serogroup of spirochete Leptospira show fastidious
      growth with more exigent nutritional requirements than those of other Leptospira
      pathogenic strains. The influence of 37 nutritional compounds on the growth of
      Leptospira interrogans serogroup Ballum was investigated employing the synthetic
      EMJH medium as the base for the study. Microbial growth was estimated
      spectrophotometrically and direct counts were performed with a Petroff-Hausser
      counting chamber. Virulence stability was evaluated by calculating the mean
      lethal dose in hamsters. Antigenicity stability was evaluated by Western blotting
      using a specific antiserum. Cell yields commonly obtained in EMJH were
      triplicated without virulence or antigenicity depletions after culturing in a
      modified EMJH medium with an increased concentration of Tween 80, and the
      incorporation of sodium acetate and beef extract. Neither the increased
      concentration of at least 6 components of EMJH nor the incorporation of a variety
      of new nutrients stimulated cell yields or the growth rate of the microorganism.
      The results allow us to make use of an enriched culture medium that promotes high
      cell yields of this fastidious serogroup most prevalent in humans in Cuba.

PMID- 17037251
TI  - [Optimization of the growth of Paenibacillus larvae in semi-selective media].
AB  - The sensitivity of media MYPGP, MYPGP(NALPIA) A (6 microg/ml nalidixic acid and
      10 microg/ml pipemidic acid) and MYPGP(NALPIA) B (9 microg/ml nalidixic acid and
      20 microg/ml pipemidic acid) for the recovery of viable spores of Paenibacillus
      larvae from honey, was evaluated by using different incubation times and
      different spore concentrations. No significant differences between incubation
      times, spore concentration or culture media were found. In the case of the
      recovery of vegetative cells from PBS at different incubation times and different
      dilutions no significant differences were found between the incubation times or
      the dilutions tested, while significant differences were found in the three media
      when compared with one another, MYPGP(NALPIA)B providing the lowest recovery of
      vegetative cells. Considering these results, we propose the use of MYPGP(NALPIA)B
      to recover spores of P. larvae from honey, specially for honeys with
      heterogeneous populations of bacterial spores; when culturing vegetative cells,
      MYPGP or MYPGP(NALPIA)A must be used to obtain good growth.

PMID- 17037252
TI  - [Helicobacter pylori and active chronic gastritis].

PMID- 17037253
TI  - [Recombinant baculovirus as immunogens].

PMID- 17037254
TI  - [Detection of anti-Brucella spp. antibodies in swine by agglutination techniques
      and indirect ELISA in the Buenos Aires and La Pampa provinces, Argentina].
AB  - Porcine brucellosis is one of the most important zoonoses in this country.
      Currently, there is no control program for porcine brucellosis in Argentina and
      the epidemiological situation is still unknown. The purpose of our study was to
      detect anti-Brucella spp. antibodies in swine in the southwest of the Buenos
      Aires province and the east of the La Pampa province. Blood samples were obtained
      when animals were slaughtered. The presence of anti-brucella antibodies was
      studied by the buffered plate agglutination test (BPA), the tube agglutination
      test (SAT), the 2-mercaptoethanol (2-ME) agglutination test and indirect ELISA
      tests, using the cytosolic fraction from Brucella abortus S19 (CYT), and
      lipopolysaccharide (LPS)-free cytosolic proteins (CP). Out of a total of 325
      samples analyzed, 17.8% reacted positively to BPA, 13.8% to SAT, 8.0% to 2-ME,
      21.0% to ELISA-CYT and 10.0% to ELISA-CP. These results agree with the few data
      available in our country and suggest that brucellosis screening should be
      extended to other regions.

PMID- 17037255
TI  - [Histoplasma capsulatum with aberrant morphology isolated in Argentina].
AB  - For the first time in Argentina, we describe a strain of Histoplasma capsulatum
      var. capsulatum with an aberrant morphology that was isolated from a single
      patient with AIDS. Mycelial phase cultures on agar Sabouraud at 25-28 degrees C
      showed white, glabrous, umbilicated and centrally radiated colonies. Unusual
      microscopic findings were the absence of typical conidia, the presence of
      terminal/intercalary chlamydoconidia with a diameter of 4 pm and of thickened
      hyphae. Fungal identification was confirmed by the detection of bands H and M
      species specific antigens in mycelial culture supernatants and reversion to the
      typical yeast phase on agar brain-heart-cysteine at 37 degrees C. The genomic DNA
      profile obtained by RAPD-PCR with primers 1281-1283 coincided with the
      predominant profile of H. capsulatum among isolates from Argentine patients.

PMID- 17037256
TI  - [Genetic environment of CTX-M-2 in Klebsiella pneumoniae isolates from
      hospitalized patients in Uruguay].
AB  - We studied two CTX-M-2-producing Klebsiella pneumoniae clinical strains, K96005
      and K13, isolated from hospitalized patients in Uruguay, during 1996 and 2003,
      respectively. The genomic surroundings of bla(CTX-M-2) were characterized by PCR
      mapping and DNA sequencing. Our results show that blaCTX-M-2 is included in a
      complex class-1 integron (InK13), associated with an orf513 in both isolates. The
      genetic array of the integron, aac(6')-lb, bla(OxA,2), orfD (gene cassette
      region), associated with an orf513-bla(CTX-M-2), seems to be widely disseminated
      over the Rio de la Plata region.

PMID- 17037257
TI  - [Inhibition of Paenibacillus larvae employing a mixture of essential oils and
      thymol].
AB  - In vitro antimicrobial activity of a mixture of two essential oils and thymol
      against Paenibacillus larvae, causal agent of American Foulbrood (AFB), was
      evaluated. The essential oils were extracted from cinnamon (Cinnamomum
      zeylanicum) and thyme (Thymus vulgaris). The third component used, thymol, is the
      major component of the essential oil of thyme which contains 39.9% of thymol.
      Minimal inhibitory concentration (MIC) in Mueller-Hinton broth by the tube
      dilution method and minimal bactericide concentration (MBC) on MYPGP agar were
      evaluated. Thyme registered MIC values of 150-250 microg/ml and MBC values of 200
      300 microg/ml, while the MIC and MBC values obtained for cinnamon were of 50-100
      microg/ml and 100-125 microg/ml. Thymol showed similar MIC and MBC values of 100
      150 microg/ml. No significant differences between the bacterial strains were
      detected, but significant differences between essential oils and thymol activity
      were registered (P<0,01). An inhibitory synergetic effect on AFB was observed
      reducing MIC and MBC values due to the use of a mixture of 62.5% of thyme, 12.5%
      of cinnamon and 25% of thymol.

PMID- 17037258
TI  - [Moulds and yeasts in bottled water and soft drinks].
AB  - Some damaged cartons of soft drinks and carbonated water were analyzed to detect
      the microorganisms that caused the damage. The contaminants of sugar used in the
      production of one of the drinks were also studied. The methods of Deak & Beuchat
      and Pitt & Hocking were used for the identification of yeasts and moulds,
      respectively. The agents of the spoilage of soft drinks were Debaryomyces
      hansenii, Debaryomyces polymorphus, Galactomyces geotrichum, Metschnikowia
      pulcherrima, Mucor circinelloides, Pichia anomala, Pichia jadinii, Pichia
      subpelliculosa, Rhodotorula glutinis and Zygosaccharomyces bailii. The
      microorganisms found in sugar were Aspergillus niger, Aspergillus penicilloides,
      Aspergillus versicolor, Cladosporium sphaerospermum, Mucor racemosus, P. anomala
      and Rhizopus stolonifer. Paecilomyces fulvus and Penicillium glabrum were
      observed in carbonated water.

PMID- 17037259
TI  - [Mechanisms of action of and resistance to rifampicin and isoniazid in
      Mycobacterium tuberculosis: new information on old friends].
AB  - Human tuberculosis is still one of the most frequent causes of death worldwide.
      Despite the implementation of therapeutic regimes combining four drugs, the rise
      of resistant and multidrug-resistant Mycobacterium tuberculosis strains has
      compromised their efficacy. Two of the most effective anti-tubercular drugs in
      use, rifampicin and isoniazid, have been closely studied due to their therapeutic
      importance. These studies have led to the identification of the genes involved in
      resistance mechanisms and of those encoding the molecular targets for these
      drugs. Rifampicin is an inhibitor of the beta-subunit of the RNA polymerase of
      prokaryotes, including M. tuberculosis. Resistance to rifampicin is mediated by
      mutations clustered in a small region of the rpoB gene. A fraction of resistant
      strains showed no mutations in rpoB, suggesting that other mechanisms of
      resistance, possibly efflux pumps, may exist. Isoniazid is a pro-drug activated
      by KatG, a catalase-peroxidase. Mutations in katG, the most commonly found in M.
      tuberculosis clinical isolates, give high levels of resistance. In spite of this,
      the molecular target for isoniazid is InhA, an enoyl-ACP-reductase involved in
      the biosynthesis of mycolic acids. Other mutations causing resistance to
      isoniazid have been mapped to ndh, a gene encoding the NADH dehydrogenase.

PMID- 17037260
TI  - Phase I studies of chemotherapeutic agents in cancer patients: a review of the
      designs.
AB  - I review the designs available for Phase I dose-finding studies of
      chemotherapeutic agents in cancer patients. The designs are based on the
      assumption that both efficacy and toxicity increase with dose, and thus attempt
      to minimize the number of patients treated at low doses, and also to minimize the
      chance that patients will be treated at excessively toxic or lethal doses. The
      designs fall into two classes: rule-based and model-guided. Rule-based designs
      can always determine a reasonable maximum tolerable dose based on observed
      toxicity, but when model assumptions are not satisfied, many model-guided designs
      will not.

PMID- 17037261
TI  - Sequential designs for logistic phase I clinical trials.
AB  - Both parametric and nonparametric sequential designs and estimation methods are
      implemented in phase I clinical trials. In this article, we take a systematic
      approach, consisting of a start-up design, a follow-on design, a sequential dose
      finding design, and an estimation method, to find an efficient estimate of the
      maximum tolerated dose under the assumption that the dose-response curve has a
      true underlying logistic distribution. In particular, for the problem of the
      nonexistence of the maximum likelihood estimates of the logistic parameters, a
      constraint on the probability of an undetermined maximum likelihood estimator
      (MLE) is incorporated into the parametric sequential designs. In addition, this
      approach can also be extended to incorporate ethical considerations, which
      prohibit an administered dose from exceeding the maximum acceptable dose.
      Comparison based on simulation studies between the systematic designs and
      nonparametric designs are described both for continuous dose spaces and discrete
      dose spaces, respectively.

PMID- 17037262
TI  - Adaptive dose selection using efficacy-toxicity trade-offs: illustrations and
      practical considerations.
AB  - The purpose of this paper is to describe and illustrate an outcome-adaptive
      Bayesian procedure, proposed by Thall and Cook (2004), for assigning doses of an
      experimental treatment to successive cohorts of patients. The method uses
      elicited (efficacy, toxicity) probability pairs to construct a family of trade
      off contours that are used to quantify the desirability of each dose. This
      provides a basis for determining a best dose for each cohort. The method combines
      the goals of conventional Phase I and Phase II trials, and thus may be called a
      "Phase I-II" design. We first give a general review of the probability model and
      dose-finding algorithm. We next describe an application to a trial of a biologic
      agent for treatment of acute myelogenous leukemia, including a computer
      simulation study to assess the design's average behavior. To illustrate how the
      method may work in practice, we present a cohort-by-cohort example of a
      particular trial. We close with a discussion of some practical issues that may
      arise during implementation.

PMID- 17037263
TI  - Design and analysis of dose-finding studies combining multiple comparisons and
      modeling procedures.
AB  - The search for an adequate dose involves some of the most complex series of
      decisions to be made in developing a clinically viable product. Typically
      decisions based on such dose-finding studies reside in two domains: (i) "proof"
      of evidence that the treatment is effective and (ii) the need to choose dose(s)
      for further development. We consider a unified strategy for designing and
      analyzing dose-finding studies, including the testing of proof-of-concept and the
      selection of one or more doses to take into further development. The methodology
      combines the advantages of multiple comparisons and modeling approaches,
      consisting of a multi-stage procedure. Proof-of-concept is tested in the first
      stage, using multiple comparison methods to identify statistically significant
      contrasts corresponding to a set of candidate models. If proof-of-concept is
      established in the first stage, the best model is then used for dose selection in
      subsequent stages. This article describes and illustrates practical
      considerations related to the implementation of this methodology. We discuss how
      to determine sample sizes and perform power calculations based on the proof-of
      concept step. A relevant topic in this context is how to obtain good prior values
      for the model parameters: different methods to translate prior clinical knowledge
      into parameter values are presented and discussed. In addition, different
      possibilities of performing sensitivity analyses to assess the consequences of
      misspecifying the true parameter values are introduced. All methods are
      illustrated by a real dose-response phase II study for an anti-anxiety compound.

PMID- 17037264
TI  - Hypothesis testing and Bayesian estimation using a sigmoid Emax model applied to
      sparse dose-response designs.
AB  - Application of a sigmoid Emax model is described for the assessment of dose
      response with designs containing a small number of doses (typically, three to
      six). The expanded model is a common Emax model with a power (Hill) parameter
      applied to dose and the ED50 parameter. The model will be evaluated following a
      strategy proposed by Bretz et al. (2005). The sigmoid Emax model is used to
      create several contrasts that have high power to detect an increasing trend from
      placebo. Alpha level for the hypothesis of no dose-response is controlled using
      multiple comparison methods applied to the p-values obtained from the contrasts.
      Subsequent to establishing drug activity, Bayesian methods are used to estimate
      the dose-response curve from the sparse dosing design. Bayesian estimation
      applied to the sigmoid model represents uncertainty in model selection that is
      missed when a single simpler model is selected from a collection of non-nested
      models. The goal is to base model selection on substantive knowledge and broad
      experience with dose-response relationships rather than criteria selected to
      ensure convergence of estimators. Bayesian estimation also addresses deficiencies
      in confidence intervals and tests derived from asymptotic-based maximum
      likelihood estimation when some parameters are poorly determined, which is
      typical for data from common dose-response designs.

PMID- 17037265
TI  - Bayesian optimal designs for a quantal dose-response study with potentially
      missing observations.
AB  - In a dose-response study, there are frequently multiple goals and not all planned
      observations are realized at the end of the study. Subjects drop out and the
      initial design can be quite different from the final design. Consequently, the
      final design can be inefficient. Single- and multiple-objective Bayesian optimal
      designs that account for potentially missing observations in quantal response
      models were recently proposed in Baek (2005). In this work, we investigate the
      efficiencies of the conventional optimal designs that do not incorporate
      potential missing information relative to our proposed designs. Furthermore, we
      examine the impact of restricted dose range on the resulting optimal designs. As
      an application, we used missing data information from a study by Yocum et al.
      (2003) to design a study for estimating dose levels of tacrolimus that will
      result in a certain percentage of rheumatoid arthritis patients having an ACR20
      response at 6 months.

PMID- 17037266
TI  - A Bayesian design and analysis for dose-response using informative prior
      information.
AB  - We wish to use prior information on an existing drug in the design and analysis
      of a dose-response study for a new drug candidate within the same pharmacological
      class. Using the Bayesian methodology, this prior information can be used
      quantitatively and the randomization can be weighted in favor of the new
      compound, where there is less information. An Emax model is used to describe the
      dose-response of the existing drug. The estimates from this model are used to
      provide informative prior information used for the design and analysis of the new
      study to establish the relative potency between the new compound and the existing
      drug therapy. The assumption is made that the data from previous trials and the
      new study are exchangeable. The impact of departures from this assumption can be
      quantified through simulations and by assessing the operating characteristics of
      various scenarios. Simulations show that relatively modest sample sizes can yield
      informative results about the magnitude of the relative potency using this
      approach. The operating characteristics are good when assessing model estimates
      against clinically important changes in relative potency.

PMID- 17037267
TI  - Multiple comparisons and multiple contrasts in randomized dose-response trials-
      confidence interval oriented approaches.
AB  - According to the ICH E9 recommendation, the evaluation of randomized dose-finding
      trials focuses on the graphical presentation of different kinds of simultaneous
      confidence intervals: i) superiority of at least one dose vs. placebo with and
      without the assumption of order restriction, ii) noninferiority of at least one
      dose vs. active control, iii) identification of the minimum effective dose, iv)
      identification of the peak dose, v) identification of the maximum safe dose for a
      safety endpoint, and vi) estimation of simultaneous confidence intervals for
      "many-to-one-by-condition interaction contrasts." Moreover, global tests for a
      monotone trend or a trend with a possible downturn effect are discussed. The
      basic approach involved obtaining multiple contrasts for different problem
      related contrast definitions. For all approaches, definitions of relevance
      margins for superiority or noninferiority are needed. Because consensus on
      margins only exists for selected therapeutic areas and the definition of absolute
      thresholds may be difficult, simultaneous confidence intervals for ratio to
      placebo were also used. All approaches are demonstrated in an example-based
      manner using the R-packages multcomp (difference), for hypotheses based on
      difference, and mratios (ratio), for hypotheses based on ratios.

PMID- 17037268
TI  - Using the partitioning principle to adaptively design dose-response studies.
AB  - An adaptive two-stage design is proposed for dose-response studies to find the
      minimum effective dose. The procedure is conducted in a stepwise fashion based on
      the partition testing principle with familywise error rate controlled strongly.
      We examine a wide dose range vs. a placebo in the first stage. Then an interim
      analysis is conducted with potential modification of design features of the
      experiment. Ineffective and/or unsafe dose treatments are terminated, and
      selected doses are further investigated in the second stage. Inference is based
      on a pre-chosen conditional error function. Several conditional error functions
      are discussed and compared.

PMID- 17037269
TI  - Fallback tests in dose-response clinical trials.
AB  - This article introduces a general testing procedure for performing dose-control
      comparisons in dose-response trials with one or more endpoints. The procedure
      (termed multi-stage fallback procedure) is an extension of the fallback test
      proposed by Wiens (2003). The multi-stage fallback procedure features a simple
      stepwise form and improves the power of dose-control tests at higher doses by
      taking into account the ordering of the doses. It also serves as an efficient
      tool for handling multiplicity caused by multiple endpoints. It is shown in this
      article that the multi-stage fallback procedure can be formulated as a closed
      testing procedure and thus controls the Type I error rate with respect to
      multiple dose-control comparisons as well as multiple endpoints. The proposed
      testing method is illustrated using examples from dose-response clinical trials
      with single and multiple endpoints.

PMID- 17037270
TI  - The grade is: 66 out of 100. Commonwealth gives U.S. healthcare a sickly ranking,
      but some say it's time to offer solutions, not point out problems.
AB  - When the Commonwealth Fund issued its first scorecard on the U.S. healthcare
      system, the news wasn't so great. But the project's authors said the score of 66
      points out of 100 shouldn't be interpreted as a failing grade, but a sign the
      nation can do much better. The U.S. spends 16% of its GDP on healthcare, said
      Karen Davis, president of the Commonwealth Fund. "We are not getting good value
      for that investment."

PMID- 17037271
TI  - IOM's pay-for-performance fix. Plan would trim all payments, pool money for
      rewards.

PMID- 17037272
TI  - Calif. Blue Cross fined $200K. Insurer allegedly dropped member to avoid payment.

PMID- 17037273
TI  - La. elder-care providers indicted.

PMID- 17037274
TI  - The price club. Why a boatload of transparency projects don't have a chance of
      reaching shore.

PMID- 17037275
TI  - 21st annual Design Awards. With the patient in mind. Simplicity, harmony with
      environment distinguish winners..

PMID- 17037276
TI  - Quantification of left ventricular regional functions using ECG-gated myocardial
      perfusion SPECT--validation of left ventricular systolic functions--.
AB  - OBJECTIVE: We have developed a program to quantify regional left ventricular (LV)
      function and wall motion synchrony using ECG-gated myocardial perfusion SPECT
      (MPS). This preliminary study was undertaken to validate the use of this program
      for estimating regional LV systolic function. METHODS: Patients were subjected to
      MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed
      to have a low probability of coronary artery disease (LPG; low probability
      group), 19 heart disease patients who were examined by MPS and equilibrium
      radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were
      examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The
      values of the ejection fraction (EF) and peak ejection rate (PER) were estimated.
      The global functions evaluated by this program were compared with those obtained
      by ERNA in the ERG. For regional assessment, the reference values of the
      functional indices were obtained for 17 LV segments in LPG. The Z score,
      (reference average value of the segment--patient's value of the
      segment)/reference standard deviation of the segment, was used for the evaluation
      of regional functions; a score equal to or greater than 2 was defined as
      abnormal. Semiquantitative visual interpretation of 2DE was used as the standard
      to assess wall motion. The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) of these criteria and the relationship
      between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of
      the global EF and PER evaluated by this program correlated with those determined
      by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The
      sensitivities of regional EF and PER for segmental wall motion abnormalities were
      86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%,
      respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were
      96.0% and 91.7%, respectively. The Z scores of these indices significantly
      correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p
      < 10(-10)). CONCLUSION: The potential of this program to quantify the regional
      systolic function was validated.

PMID- 17037277
TI  - The measurement of willingness to pay for mass cancer screening with whole-body
      PET (positron emission tomography).
AB  - OBJECTIVE: Recently, we have seen an increase in the number of studies that
      measured the willingness to pay (WTP) for medical services using the contingent
      valuation method (CVM) and evaluated the benefits of these services. This study
      aimed to measure the general public's WTP for cancer screening with positron
      emission tomography (PET) and to determine consumer characteristics that may
      affect their WTP. METHODS: A questionnaire survey of males and females living in
      Japan aged between 40 and 59 years was conducted via the Internet. A total of 274
      individuals accepted the offer to participate and were enrolled in the study. The
      study participants were divided into two groups: Group A (n = 138) and Group B (n
      = 136). Group A was provided only with information about the PET procedure and
      the high cancer detection rate; Group B was provided with additional information
      regarding the possibility of 'false negative' and 'false positive' results and
      the fact that the efficacy of PET screening for reducing mortality has not yet
      been demonstrated. Participants were then asked to answer their WTP for cancer
      screening with PET by paymentcards approach. RESULTS: The overall average amount
      consumers were willing to pay for PET cancer screening was dollars 103.7 (n =
      274). The average value in Group A was dollars 107.3, the average value in Group
      B was dollars 100.0 and there was no statistically significant difference between
      the groups. The results of categorical regression analysis showed that household
      annual income was the only significant factor affecting WTP. CONCLUSIONS: Our
      study showed that household annual income affected the WTP for cancer screening
      with PET and therefore the demand for PET screening would be limited to the high
      income group. Negative information about PET did not reduce the WTP. This finding
      suggests that test subjects mainly evaluated the high detection rate of PET
      screening and the 'reassurance' value of receiving negative screening results.

PMID- 17037278
TI  - Tumor viability evaluation by positron emission tomography with [18F]FDG in the
      liver metastasis rat model.
AB  - We prepared a liver metastatic tumor model by injection of rat colon
      adenocarcinoma cells to Fischer F344 rats through portal vein, and applied
      positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose
      ([18F]FDG) ([18F]FDG-PET) to this model. At an early stage of the model, multiple
      small tumor nodules appeared in the inferior lobes of the livers, and extended
      later into the superior lobes. To evaluate the tumor growth and tumor viability
      at the early stage, we proposed a new concept, tumor viability index (TVI),
      instead of the standardized uptake value (SUV) of the [18F]FDG uptake. The TVI
      was defined by subtracting the signal based on the normal liver from the total
      signal in the whole liver including tumor nodules: (whole liver SUV-normal liver
      SUV) x ml of whole liver region of interest (ROI). For the signal of the whole
      liver, ROIs were placed on six slices covering the whole liver, and the ROI of
      normal liver region was located in the superior lobe of the liver. The average
      TVI values increased with tumor growth and significantly correlated with the
      numbers of tumor nodules. The new concept may be useful for evaluating the tumor
      viability non-invasively and quantitatively by [18F]FDG-PET.

PMID- 17037279
TI  - Contribution of 99mTc-sestamibi infusion SPECT to the characterization of fixed
      perfusion defects.
AB  - In patients with coronary artery disease, the distinction between scar and viable
      myocardium by means of myocardial perfusion imaging (MPI) sometimes can be
      difficult because of the equivocal meaning of fixed perfusion defects. In this
      study we examined whether addition of a 99mTc-sestamibi infusion study to the
      standard MPI could provide extra information regarding the fixed defects. Thirty
      seven patients underwent standard MPI and an extra SPECT study in which 99mTc
      sestamibi was given as a prolonged constant infusion. Of 324 myocardial segments
      available for analysis, 134 had fixed or resting perfusion abnormalities on
      standard MPI studies, of which 25% (33/134) in 12 patients showed partial
      improvement in the perfusion pattern whereas in 6% (8/134) the improvement was
      very significant in infusion studies. In 19 patients who were also examined with
      dobutamine echocardiography, 13 showed concordance between echocardiography and
      infusion MPI. This study suggests that infusion MPI may provide complementary
      information to the conventional scintigraphy with regard to interpretation of
      standard myocardial perfusion scans with fixed defects.

PMID- 17037280
TI  - New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization
      method.
AB  - We evaluated a new semiquantitative procedure to more easily and objectively
      estimate the striatal uptake of 123I-FP-CIT in patients with Parkinsonian
      syndrome (PS) and essential tremor (ET), using an anatomical standardization
      method, the Neurostat. METHODS: Eleven patients with PS and 8 with ET were
      examined by clinical assessment and 123I-FP-CIT SPECT imaging. The modified Hoehn
      and Yahr Staging Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were
      used to assess the stage and severity of the disease. The co-registered MR and
      SPECT images were created with fusion software included in Neurostat. On the
      cross section, which shows the largest area of striate, irregular shaped regions
      of interest corresponding to the striate and occipital cortex were drawn. Then
      the ratio of specific striatal uptake to non-specific occipital cortex, V3"(F),
      was calculated. Another calculation was done by VOIClassic, which is a software
      included in Neurostat to estimate the counts per voxel of anatomically defined
      regions such as caudate nucleus, putamen, occipital cortex, and total cortex.
      Using these count data, the ratio of specific striatal uptake to non-specific
      occipital cortex, V3"(OC), and total cortex, V3"(TC), was calculated. RESULTS: A
      fair linear correlation was observed between V3"(OC) and V3"(F) (y = 1.53x +
      1.40; r = 0.756; p < 0.01), as well as between V3"(TC) and V3"(F) (y = 1.24x +
      1.43; r = 0.713; p < 0.01). Both V3"(OC) and V3"(TC) yielded similar tendencies.
      Concerning discrimination between ET and PS, there was a significant difference
      between the mean V3" of PS and ET (p < 0.01). Concerning the correlation between
      V3" value and the severity of PS, the UPDRS motor score significantly correlated
      with the V3"(F) value (rs = -0.816). However, V3"(OC) and V3"(TC) correlated less
      with UPDRS (rs = -0.667 and -0.645, respectively). CONCLUSIONS: Semiquantitative
      parameters, V3"(OC) and V3"(TC), calculated by VOIClassic including the Neurostat
      system are useful and easily calculable parameters as well as V3"(F) for the
      differential diagnosis of PS from ET.

PMID- 17037281
TI  - Fluctuation of adenosine concentration by modes of intravenous infusion based on
      mathematical simulation and experiments.
AB  - OBJECTIVE: Adenosine, which has been used for a myocardial perfusion scan, shows
      rapid clearance from blood because of its short half-life of <10 seconds. This
      simulation study evaluates influences of modes of radionuclide injection on
      ventricular adenosine concentration when one intravenous injection line is used.
      METHODS: Assuming that radionuclide injection is a unit impulse, time-activity
      curves were measured in the left ventricle (LV) and fitted by a gamma function.
      Typical patterns of concentration fluctuation when adenosine infusion was
      temporarily modified were calculated by the convolution integral of input
      function and unit impulse response. Variation of concentration was measured by
      experiments using continuous 99mTc injection and co-infusion of water via a three
      way stopcock. Modes of co-infusion with various infusion speeds and volumes were
      examined. RESULTS: Intermission of adenosine infusion and rapid displacement by
      radionuclide co-injection significantly influenced the adenosine concentration in
      LV. Intermission of adenosine infusion for 2 seconds caused a 15% decrease in the
      adenosine concentration in the left ventricle. When a square-shaped input was
      assumed, a three-fold higher concentration of adenosine for 3 seconds created by
      radionuclide injection resulted in a +42% increase in the LV concentration. Based
      on a measured input function, radionuclide injection using three-way stopcock
      through one route caused a two- to three-fold increase in the steady
      concentration in the vein just after injection. When 0.5 ml of radionuclide was
      slowly co-injected, with three ways opened, it caused a relatively low
      fluctuation, creating a +34% to -47% change in concentration of LV. A flush of
      radionuclide with physiological saline significantly increased the adenosine
      concentration in LV, when short half-lives were assumed. CONCLUSION: An
      intravenous adenosine and radiopharmaceutical injection in the same line is
      feasible. However, the fluctuation of concentration depends significantly on the
      mode of injection. To minimize the fluctuation, a slow injection of a small
      volume of a myocardial imaging agent via a co-injection route, with three ways
      opened, is recommended.

PMID- 17037283
TI  - Respiratory distress caused by radioiodine therapy in patients with
      differentiated thyroid cancer.
AB  - Respiratory distress accompanied by stridor is an uncommon complication of 131I
      radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours
      of treatment. This report presents three cases with papillary thyroid carcinoma
      in which 131I therapy caused this acute complication. One of them had no apparent
      risk for this complication such as the existence of remnant thyroid tissue or
      laryngeal problems before the treatment. These cases remind physicians that 131I
      therapy is not a simple, riskless procedure.

PMID- 17037282
TI  - Brain and whole body distribution of N-isopropyl-4-iodoamphetamine (I-123) in
      humans: comparison of radiopharmaceuticals marketed by different companies in
      Japan.
AB  - OBJECTIVE: Iodine-123 (123I)-labeled N-isopropyl-4-iodoamphetamine (IMP) has been
      used as a cerebral blood flow (CBF) tracer for single-photon emission computed
      tomography (SPECT). An autoradiographic (ARG) method has been developed for the
      quantitation of CBF by IMP and SPECT. Two IMPs (IMPA and IMPB) produced by
      different radiopharmaceutical companies are marketed in Japan. In the present
      study, whole-body distributions including brain and blood of the two IMPs were
      compared in the same human subjects. METHODS: Two brain SPECT studies using IMPA
      or IMPB were performed on separate days in six young healthy men. Whole-body
      scans were also obtained with a large field-of-view single-head gamma camera. One
      point arterial blood sampling was performed at 10 min after injection of IMP to
      measure both the radioactivity concentrations of whole blood and of octanol
      extracted components. RESULTS: No significant differences between the two tracers
      were observed in body distribution, tracer kinetics in brain, or regional
      distribution in brain. However, the octanol extraction fraction in blood was
      significantly different between the two tracers. Radiochemical purity was
      slightly but significantly different between the tracers. CONCLUSIONS: In the ARG
      method, arterial input function is determined by calibration of a standard input
      function with the radioactivity concentration of arterial whole blood. Because
      the standard input function in the ARG method was obtained using IMPA, the
      standard input function obtained for IMPB should be used when CBF is calculated
      by the ARG method with IMPB.

PMID- 17037284
TI  - [Disturbances in aggregability of red blood cells in essential hypertension].
AB  - The study was performed to find the relationship between rheological properties
      of erythrocytes and the effectiveness of antihypertensive therapy both in
      patients suffering from essential hypertension as well as in spontaneously
      hypertensive rats (SHR). Additionally, in patients receiving the same
      antihypertensive therapy we evaluated the effect of aspirin at a low and high
      dose on aggregation of erythrocytes. We found that in a consequence of uniformed
      antihypertensive therapy which in patients lasted minimum one year and consisted
      of one of ACE inhibitors (enalapril or perindopril or captopril), one of beta
      antagonists (metoprolol or bisoprolol) and diuretic agent (indapamid), while SHR
      lasted 8 days and consisted of ACE inhibitor (chinapril), blood pressure lowered
      and red blood cell rheology was significantly improved. For the first time we
      observed that antihypertensive treatment which advantageously decreased the
      aggregability of erythrocytes was diminished by a high dose of aspirin (300
      mg/day).

PMID- 17037285
TI  - [Fibrinogen--acute phase protein as a marker of immunological process as
      atherosclerosis].
AB  - The most important CAD risk factors are: smoking, high level of LDL-cholesterol
      and low level of HDL-cholesterol, hypertriglyceridemia, diabetes, obesity,
      hypertension, men sex, age over 45 in men and over 55 in women. Carl von
      Rokitanski was the first who suggested the role of thrombosis and fibrynolisis in
      the development of atherosclerosis and was the author of thrombolic theory. The
      recently studies show that atherosclerosis is an immuno-inflamatory process.
      Fibrinogen as an acute phase protein is a new marker of ischemic heart disease
      and its role in atherosclerosis needs further investigations.

PMID- 17037286
TI  - [The functional relevance of Arg16Gly and Gln27Glu-beta2-adrenoreceptor
      polymorphism in patients with asthma and allergic rhinitis].
AB  - The objective of the present study was to investigate the effect of beta2
      adrenoreceptor polymorphisms Arg16Gly and Gln27Glu as well as their relationship
      to the pulmonary function parameters, and the clinical presentation in patients
      with asthma and allergic rhinitis. Investigated polymorphisms were in linkage
      disequilibrium, therefore their effects should be evaluated collectively.
      Although no significant association could be found with the presence of asthma or
      allergic rhinitis in studied population, polymorphisms of beta2-adrenoreceptor
      can influence pulmonary function in these patients. These effects significantly
      differ between men and women, possibly indicating the effect of sex hormones on
      genetic regulation of pulmonary function.

PMID- 17037287
TI  - 24-hour heart rate variability in patients with gastroesophageal reflux disease.
AB  - The GERD pathogenesis may be associated with disturbances of the autonomic
      nervous system (ANS), which can be revealed using heart rate variability studies
      (HRV). The aim of presented study was to estimate the circadian ANS activity in
      24-hour HRV recordings in GERD patients, both in non-erosive form (NERD), and
      with erosive, inflammatory changes in the esophagus (ERD patients). Our results
      demonstrated disturbances in the parasympathetic ANS part, but they also
      delivered the proofs for possible sympathetic disorder. That is why the autonomic
      neuropathy in GERD patients may have mixed character.

PMID- 17037288
TI  - [Motor and endocrine function disturbances of the gastrointestinal tract in
      patients with chronic renal failure (CRF)].
AB  - In the chronic renal failure (CRF) there are several upper gastrointestinal
      symptoms, which result from both disturbed motor function (associated with the
      delayed gastric emptying) and myoelectrical one (associated with abnormal
      electrogastrography registration). In patients suffering from CRF, disturbances
      of the endocrine digestive system function were also demonstrated, which are
      related to the observations of many gastrointestinal hormones increased levels.

PMID- 17037289
TI  - Mechanisms of intestinal dysmotility in morphine dependence: whether central or
      peripheral?
AB  - Changes of intestinal motility and transit due to morphine administration are
      attributed to its central and peripheral action, however coexistence of both
      central and peripheral mu receptors in morphine dependence hasn't been clearly
      demonstrated so far. Our purpose was the evaluation of the effect of either CNS
      or ENS mu receptor blockade on intestinal motility in morphine dependent rats.
      Twenty male rats were subjected to chronic subcutaneous morphine infusions for 72
      hrs. On each day motility indices (MI) were analysed in the animals' duodenum and
      ascending colon before and after either intraperitoneal (IP) or
      intracerebroventricular (ICV) mu antagonist (CTOP) administration. Tolerance of
      the intestinal motility to morphine developed in both the duodenum and the
      ascending colon after 72 hrs of the infusion. Dependence was observed at 24 hrs
      and maintained at 48 and 72 hrs of morphine administration. On each day no
      differences of MI reaction to mu blockade were visible regarding the IP or ICV
      CTOP administration. Our results suggest the involvement of both the CNS and the
      ENS mu opioid receptors in mechanisms of the intestinal tolerance to and
      dependence upon morphine.

PMID- 17037290
TI  - [Gastric myoelectrical dysfunction in patients with hematoma of the posterior
      cranial fossa].
AB  - Demonstrated disturbances of gastric myoelectrical activity in 10 patients with
      hematoma of the posterior cranial fossa. Tachygastria amounts 40% of the
      recording time.

PMID- 17037291
TI  - [Preoperative diagnostics in patients with adrenal tumors].
AB  - The aim of the study was analysis of preoperative diagnostics of patients who
      underwent laparoscopic adrenalectomy. In the preoperative diagnostics in 10
      patients (22.2%) pheochromocytoma was found, in 8 (17.8%) Conn's syndrome, in 4
      (8.9%) Cushing's syndrome and in 1 (2.2%) adrenal virilization. Full accordance
      between histopathological findings and preoperative diagnosis was achieved in 91%
      of cases. Four cases of discrepancy were: 1 false positive preoperative diagnosis
      of aldosteronoma, 1 false positive and 2 false negative diagnosis of
      pheochromocytoma.

PMID- 17037292
TI  - [Dextromethorphan enhances analgesic activity of propacetamol--experimental
      study].
AB  - While many pre-clinical and clinical studies have suggested that the addition of
      N-methyl-d--aspartate (NMDA) receptor antagonists, such as dextromethorphan, to
      opioid analgesics, such as morphine may enhance the analgesic effects. The aim of
      the study was to assess the effect of non-competitive NMDA antagonists and
      paracetamol (propacetamol) on pain threshold and analgesic potency of this drugs
      and their combinations in formalin model for pain in rats. Intraperitoneal
      administration of paracetamol only in doses of 100 g/kg or higher resulted in
      increase of pain threshold in tail flick and paw pressure tests. The results of
      our study suggest that there was no significant difference in pain threshold
      between separate administration of dextromethorphan and in combination with
      paracetamol. In a formalin model for pain we have shown that paracetamol in non
      analgesic doses (10 mg/kg) administered in combination with dextrometorphan,
      ketamine and mamantine was more effective than those drugs given separately but
      the best analgesic effect was obtained when combination of paracetamol and
      dextromethorphan was applied. The addition of higher doses of these combined
      drugs, that is paracetamol and all three NMDA antagonists did not result in
      enhancement of dose-dependant analgesia. In conclusion it should be stated that
      NMDA antagonists improve analgesic effect of paracetamol in the formalin model
      for pain. although only to a limited extend.

PMID- 17037294
TI  - [Internal medicine leading the revolution in medical care].

PMID- 17037293
TI  - [The influence of soybean riches of phytoestrogens diet in mouse testis
      histological structure].
AB  - Soybean diet, a rich source of phytoestrogenes, affects negatively on the
      potential fecundity in male mice. It causes spermatogenesis impairment which is
      manifested by changes in testicular histology. Germ epithelium becomes darker and
      sheds and a number of produced spermatozoa decreases. On the other hand a number
      of testicular macrophages significantly rises in Leydig glands.

PMID- 17037295
TI  - [Tasks in medical care in Japan and the world].

PMID- 17037297
TI  - [Scope of family doctor activity in Japan].

PMID- 17037296
TI  - [Knowledge of psychiatry necessary in primary care].

PMID- 17037298
TI  - [Liver regeneration with stem cell transplantation and its clinical application].

PMID- 17037299
TI  - [High risk pathophysiology and the molecular mechanism of arteriosclerosis].

PMID- 17037300
TI  - [Front line of molecular biological study on and therapy for pulmonary
      hypertension].

PMID- 17037301
TI  - [Function of language area in the brain].

PMID- 17037302
TI  - [New developments in therapeutics for infectious diseases].

PMID- 17037303
TI  - [Metabolic syndrome].

PMID- 17037304
TI  - [Metabolic syndrome and insulin resistance].

PMID- 17037305
TI  - [Metabolic syndrome and lipotoxicity].

PMID- 17037306
TI  - [Metabolic syndrome and aldosterone].

PMID- 17037307
TI  - [Diagnosis of metabolic syndrome].

PMID- 17037309
TI  - [Cerebrovascular diseases and RAS].

PMID- 17037308
TI  - [Therapy for metabolic syndrome].

PMID- 17037310
TI  - [Clinical significance of RAS block in heart diseases].

PMID- 17037311
TI  - [Kidney disease and RAS].

PMID- 17037312
TI  - [Pathophysiological significance of RAS in formation of arteriosclerosis].

PMID- 17037313
TI  - [Renin-angiotensin system and insulin resistance: carbohydrate-metabolism
      disorders].

PMID- 17037314
TI  - [Leukocytapheresis for inflammatory immune diseases].

PMID- 17037315
TI  - [Cytokine targetting therapy for inflammatory bowel diseases].

PMID- 17037316
TI  - [TNF targetting therapy for rheumatoid arthritis].

PMID- 17037317
TI  - [IL-6 targetting therapy for inflammatory immune diseases].

PMID- 17037318
TI  - [Anti-CD20 antibody therapy for inflammatory immune diseases].

PMID- 17037319
TI  - [Safety issues in medical care: For whom the care belongs?].

PMID- 17037320
TI  - [Safety issues in medical care: next step toward the safety standard].

PMID- 17037321
TI  - [Safety issues in medical care: present condition of medical safety management in
      hospitals].

PMID- 17037322
TI  - [ Safety issues in medical care: aiming for the safe culture].

PMID- 17037323
TI  - [Safety measures for medical care in Japan].

PMID- 17037324
TI  - [Physiopathology of lipoprotein glomerulopathy].

PMID- 17037325
TI  - [Progress in AIDS therapy].

PMID- 17037326
TI  - [Physiopathology of and therapy for aplastic anemia].

PMID- 17037327
TI  - [Clinical significance of KL-6].

PMID- 17037328
TI  - [Liver transplantation for familial amyloidosis].

PMID- 17037329
TI  - [Inflammation and oxidative stress].

PMID- 17037330
TI  - [Diagnosis of and therapy for nonalcoholic steatohepatitis].

PMID- 17037331
TI  - [Pathophysiology of and therapy for mixed connective tissue disease: recent
      progress on the study].

PMID- 17037332
TI  - [Recent progress in insulin therapy].

PMID- 17037333
TI  - [Future prospects for botulinum toxin therapy].

PMID- 17037334
TI  - [Physiopathology of and therapy for diabetic nephropathies].

PMID- 17037335
TI  - [Chronic hypersensitivity pneumonitis].

PMID- 17037336
TI  - [Present status and future prospects in non-drug therapy for arrhythmia].

PMID- 17037337
TI  - [Recent progress in diagnosis of and therapy for multiple myeloma].

PMID- 17037338
TI  - [Medical care for hyperlipidemia].

PMID- 17037339
TI  - [Etiology of and therapy for gastrointestinal stromal tumor].

PMID- 17037340
TI  - [Controlling hospital infections and the cost effectiveness].

PMID- 17037341
TI  - [CT diagnosis of coronary artery diseases].

PMID- 17037342
TI  - [Hepatectomy and perisurgical management for heavy drinker with hepatocellular
      carcinoma].
AB  - Hepatic resection is the first choice of treatment for hepatocellular carcinoma
      (HCC), and has the best results among the therapeutic options. Preoperative
      evaluation of liver function in patients and perioperative management for
      patients, to prevent postoperative complications, are very important.
      Postoperative pulmonary complications, including pneumonia and atelectasis, were
      frequently shown in patients who had past history of heavy alcohol-intake.
      Postoperative pulmonary complications in heavy drinkers were associated with
      their habit of smoking. Temperance and non-smoking should be required, when
      hepatectomy will be performed for heavy drinker.

PMID- 17037343
TI  - [How do self-help agencies work for recovery of drug dependence in Japan?].
AB  - DARC (Drug Addiction Rehabilitation Center) is the first and largest private half
      way house agency for drug addiction in Japan, in which the programs are centered
      on 12 step meetings and the staff is made up of only those recovered from drug
      dependence. The purpose of this report is to elucidate how DARC works in the
      recovery from drug dependence. We made two studies: staff in 30 DARC facilities
      and 108 users in 7 male residential facilities. The results showed that 330
      clients with drug dependence were participating in DARC programs at the time of
      research and about 600 clients use the programs each year. According to our
      research, three fourths of the users could maintain sobriety. Although many users
      had severe mental symptoms and socioeconomic difficulties, most users evaluated
      DARC programs highly to help them recover from these conditions. DARC rated
      highly because it provides companionship for recovered addicts and flexible
      frameworks to enhance drug addicts' motivation to recover, such as accepting
      dropouts and restarting programs, the provision of facilities away from areas
      where users were at high risk of relapse, and various program modalities.

PMID- 17037344
TI  - [Alcohol dependence syndrome and Before-Discharge Intervention Method (BDIM)--No.
      5. Patients' evaluation of BDIM by questionnaire survey].
AB  - One (A.I) of the authors has developed BDIM (Before-Discharge Intervention
      Method) for the purpose of making alcoholics aware of their drinking problems.
      153 patients were treated by BDIM. After the practiced BDIM, the patients
      underwent a 52 month observational period. 82 patients (53.6%) continued with
      either treatment as outpatient or inpatients, or attendance of a self-help group.
      We administered these 82 patients our questionnaire that asked for their
      assessment about the therapeutic effects of BDIM. 76 patients (49.7%) completed
      our questionnaire. Regarding the impression of family members' letters in BDIM,
      70 patients (92.1% of 76) answered that the letter have had a positive impression
      on them. 52 patients (68.4% of 76) answered that they have had very strong or
      strong impressions. The numbers of patients who have [very strong or strong]
      impression are significantly more in the abstinence group than in the drinking
      group. Also, we asked patients about which messages of spouses, daughters and
      sons in BDIM gave the strongest impression to these patients. The result showed
      that their daughter gave the strongest impression to many patients. We believe
      that their children, especially the patients' daughter's messages, have
      therapeutic effects as impact messages even though alcoholics have cognitive or
      memory disorder. Patients positively assessed that BDIM strengthened motivation
      for treatment or attendance of self-help group meetings, for abstinence and for
      the consequence to their lives. Many patients assessed that BDIM has effect on
      awareness of their drinking problems. But the ratio of positive answers about
      motivation of awareness of drinking problem is smaller than the ratio of positive
      answers about other questions. As a result, we surmised that BDIM will have the
      effect of empowerment, including the effect of awareness.

PMID- 17037345
TI  - Reliability and validity of the Japanese version of the Addiction Severity Index
      (ASI-J).
AB  - The Addiction Severity Index (ASI) is a frequently used clinical and research
      instrument that collects data from substance abusers in seven problem areas:
      medical, employment, alcohol, drug use, legal, family-social functioning, and
      psychiatric status. In each area, the ASI provides a composite score and severity
      rating that estimate the seriousness of the problem and the client's need for
      treatment. In the present study, we investigated the reliability and validity of
      the Japanese version of the ASI (ASI-J). One hundred and eleven subjects with a
      history of drug abuse were interviewed with a test battery including the ASI with
      informed consent. This revealed that: (a) the problem areas were independent of
      each other, underscoring the need for multidimensional assessment, (b) the inter
      rater correlation of severity ratings in each area ranged from 0.68 to 0.99, and
      Cronbach's alpha coefficient for the items used for the composite score in each
      area ranged from 0.57 to 0.86, indicating their reliability with the exception of
      the drug and employment areas, and (c) several composite scores were
      significantly correlated with the drug craving levels assessed by a visual
      analogue scale, the abstinence period, mental health, and/or relapse, supporting
      their concurrent and predictive validity. These results suggest that the ASI-J
      has acceptable reliability and validity.

PMID- 17037346
TI  - [The relationship between smoking behavior in young people and CYP2A6 gene
      polymorphisms, between them and personality traits assessed by NEO-FFI].
AB  - We performed a survey on nicotine dependence among young students. We examined
      the CYP2A6 gene polymorphism using PCR-RFLP. We examined the personality traits
      using NEO-FFI. Samples were taken from young students of which 87 were smokers
      and 142 were non-smokers and we tried to clarify the relationship between the
      nicotine metabolizing ability (CYP2A6), personality, and smoking behavior. As a
      result, the frequency of the CYP2A6*4C gene was significantly higher among non
      smokers than smokers, and the Openness score by NEO-FFI was higher among smokers
      than non-smokers. We concluded that the CYP2A6*4C gene and the Openness
      personality trait may be a cause of smoking among the young smokers. Therefore,
      there is a possibility that smoking behavior in youths may be affected not only
      by the CYP2A6 gene but also by the Openness personality trait.

PMID- 17037347
TI  - [Classification and virion structure of influenza virus].

PMID- 17037348
TI  - [History of influenza virus research].
AB  - I divided the history of influenza virus research into four groups according to
      the development of analysis methods. Since isolation of human influenza virus in
      1933, many works have been done. However, under the limitation of analysis
      method, progress in knowledge about influenza virus was very slow and many
      questions remained until the molecular biological methods were developed. After
      1975, by using molecular biological methods, influenza virus research progressed
      rapidly. Especially, by the application of PCR method, followed by capillary
      autosequencer, the research of influenza virus genome developed rapidly. Now, we
      can handle the influenza virus by manipulation of cloned cDNAs by reverse
      genetics.

PMID- 17037349
TI  - [Pandemic influenza measures in Japan--from the point of government].
AB  - H5N1 type avian flu infection has spread among poultry starting from Vietnam to
      southwest region countries since the end of 2003. Afterwards, the infections have
      expanded through Africa, Europe and even to worldwide. Cases of H5N1 type avian
      flu virus infections to human are increasing. So, the risk of acquiring, through
      mutation, capacity of human-to-human spread would be higher. As human has not
      been infected by such virus, it is worried that a pandemic, and even the increase
      of deaths due to this virus could be occurred. Japan produced "Pandemic Influenza
      Preparedness Action Plan" last year, and also takes genuine measures against a
      new pathogenic avian influenza virus. Various countries, including Japan, are
      trying to find positive measures towards it, although it has not been found.

PMID- 17037350
TI  - [Influenza surveillance in Japan].
AB  - In Japan, under the National Epidemiological Surveillance of Infectious Diseases,
      clinically diagnosed influenza cases have been reported by approximately 5,000
      influenza sentinel clinics and influenza virus isolation have been reported by
      prefectural and municipal public health institutes (PHIs). Influenza virus strain
      surveillance have been conducted by PHIs and National Institute of Infectious
      Diseases for selectin of vaccine strains. Weekly influenza case and influenza
      virus isolation data have been submitted to WHO FluNet website. In addition, HI
      antibody prevalence have been monitored by the National Epidemiological
      Surveillance of Vaccine-preventable Diseases. Various information about influenza
      surveillance in Japan is available on the Infectious Disease Surveillance Center
      website (http://idsc.nih.go.jp/iasr/index.html).

PMID- 17037351
TI  - [Gene expression of influenza viruses during replication].
AB  - Both transcription and replication of influenza virus genome take place in the
      nucleus of the infected cells. Initiation of mRNA synthesis requires the
      generation of capped primers cleaved from the 5' end of the host pre-mRNA by a
      cap-snatching mechanism. These transcripts are polyadenylated at their 3' ends
      when the viral polymerase stutters over a polyuridine stretch that is found 15-22
      nucleotides from the 5' end of the vRNA. Replication of the viral genome is
      achieved through primer-independent synthesis of a full-length, positive-sense
      replicative intermediate, cRNA, that is copied into vRNA. The switch from mRNA to
      template RNA(cRNA) synthesis requires antitermination activity of NP proteins not
      associated with nucleocapsids. M gene expression differs among influenza A, B and
      C viruses.

PMID- 17037352
TI  - [Review on replication cycle of influenza virus].
AB  - Influenza virus belongs to Orthomyxoviridae, which replicates its genome in
      nuclei of host cells. Replication requires binding to the cellular receptor,
      entry into host cytoplasm and other several steps followed. In this article,
      recent findings of the virus replication steps, particularly emphasized on
      receptor recognition, fusion process, RNP transport and assembly were reviewed.

PMID- 17037353
TI  - [Defense mechanism against respiratory infection].
AB  - Most of acute respiratory diseases are caused by infection with various viruses,
      bacteria and other microorganisms; a mixed infection with these pathogens often
      results in exacerbation of the disease. In addition to nonspecific protective
      mechanisms that constantly function in the respiratory tracts, innate and
      adaptive immunities play important roles in the protection of these pathogens.
      Secretory IgA and/or cytotoxic T cells in the mucus may be the most effective
      protection machineries of the adaptive immune systems. Recently, it has been
      proven that Toll-like receptors, each of which recognizes a conserved structure
      of pathogens, are the key molecules of the innate immune systems; this
      recognition step is considered a prerequisite for the adaptive immunity to
      function in the respiratory tracts.

PMID- 17037354
TI  - [Expression of host genes in influenza virus infected cells].
AB  - When NCI-H292 human bronchial epithelial cells were infected with influenza
      A/Udorn/72(H3N2) virus, 152 host genes were identified as virus-stimulated genes
      (VSGs). The expression of these genes was increased more than 4-fold by the virus
      infection and reached to the level of more than one copy per cell. Seventy-three
      VSGs were also stimulated by interferon-beta (IFN-beta) treatment and they
      contained the genes known to possess antiviral activity. As a likely consequence,
      the production of progeny viruses was transient in H292 cells and the cells
      survived through infection. The stimulation of the VSGs is not mediated by IFNs
      but triggered by the infection itself at least at the early phase of infection.
      In A549 human lung epithelial cells, the increase of the VSG expression was less
      than 1/6 on the average of that in H292 and virus production continued until cell
      death. These indicate that some VSGs might constitute intracellular antiviral
      mechanisms. On the other hand, the NS1 protein of influenza virus shuts off host
      gene expression by inhibiting the polyadenylation-site cleavage of host pre
      mRNAs. Therefore, balance of the shut-off and the activation of cellular genes
      during virus infection may be crucial in determining the outcome of infection.

PMID- 17037355
TI  - [Cytokines and chemokines induced by influenza virus infection].
AB  - Many kinds of cytokines and chemokines are produced in response to influenza
      virus infection through the course of cytokine cascade. Even a single cytokine
      exhibits various biological activities and different types of cells produce the
      same identical cytokine. In general, cytokines act to maintain the homeostasis of
      host condition. In influenza virus infection, it works as protective for the host
      against virus infection at its early stage, but often as pathogenic in its later
      stage. Cytokines play a pivotal role in establishment of virus specific immunity.
      However, over expression of cytokines causes irreversible severe damages to the
      host, including shock, disseminated intravascular coagulation, adult respiratory
      distress syndrome and multiple organ failure, a typical form of which is
      influenza encephalopathy. Pathogenicity of influenza virus might be determined by
      means of its potential capability to induce proinflammatory cytokines.

PMID- 17037356
TI  - [The laboratory diagnosis of influenza viruses].
AB  - The methods of the pathogen diagnosis for confirm the infection of the influenza
      virus, there are the viral isolation and the method of detected the viral
      antigen. In the each method of inspection, the time of sample extraction, the
      method of extraction and preservation must be suited to fully improve the
      sensitivity and specificity. The viral isolation is necessary and indispensable
      to analyze the antigen of the epidemic viruses and it is the high level of
      sensitivity. The several methods of detecting the antigen of the gene
      amplification include the reverse transcription polymerase chain reaction (RT
      PCR) method, the loop-mediated isothermal amplification (LAMP) method, the real
      time PCR method, and the nucleic acid sequence-based amplification (NASBA)
      method, and these methods are excellent promptly. As for these detection methods,
      being chosen according to the purpose is desirable.

PMID- 17037357
TI  - [Rapid diagnostic kits using immunochromatography for detection of influenza
      viruses].
AB  - The development of rapid diagnostic kits using immunochromatography has made it
      possible to definitively diagnose influenza A and B simply and quickly in
      outpatient services. I have studied these kits using nasopharyngeal aspirates
      from children as samples. With the most superior kit, the sensitivity to
      influenza A viruses was almost 100%, and that to influenza B viruses was 90%.

PMID- 17037358
TI  - [Treatment of influenza virus infection with anti-virals].
AB  - Dramatic advances have been made in the diagnosis and treatment of influenza in
      Japan in recent years. Most patients with influenza-like illness are now tested
      with rapid diagnostic tests, and if the results are positive, they are treated
      with neuraminidase inhibitors, mostly oseltamivir. However, we experienced
      emergence of resistant strains to oseltamivir and variable side effects.
      Zanamivir will be used widely in Japan, because it is characterized of lower rate
      of resistance. Stockpiling of those antivirals is essential for pandemic
      preparedness plan.

PMID- 17037359
TI  - [The molecular basis of resistance to anti-influenza drugs].
AB  - Influenza A viruses resistant to adamantanes(amantadine and rimantadine) have
      drastically increased in the last few years. Moreover, these adamantane-resistant
      viruses have acquired resistance without compromising viral pathogenicity and
      transmissibility. Viruses resistant to the other anti-influenza drugs,
      neuraminidase (NA) inhibitors, have also been shown to emerge at a rate higher
      than previously thought. In addition, several recent observations suggest that
      human-to-human transmission of variants resistant to NA inhibitors may have
      occurred, contrary to earlier predictions that such variants were much less
      likely to be transmitted. Although the prevalence of NA inhibitor resistants
      remains low, surveillance of drug-resistant influenza viruses in communities is
      essential. Here, we review antiviral resistance in influenza viruses and the
      molecular mechanisms of the acquisition of resistance to these drugs.

PMID- 17037360
TI  - [Development of attenuated H5N1 avian influenza vaccines using reverse genetic
      technology].
AB  - Outbreaks caused by highly pathogenic H5N1 avian influenza viruses have spread
      worldwide and the containment is impossible no longer. During the outbreaks, over
      200 human infection cases with 55% fatality are confirmed at the moment and some
      human-to -human transmission in family clusters have been observed in Vietnam,
      Thailand and Indonesia. The potency of pandemic caused by highly pathogenic H5N1
      avian influenza is increasing gradually. Consequently, development of effective
      H5N1 vaccine and its licensing for vaccination to human are urgent
      countermeasures for pandemic preparedness. In the present article, the author
      reviews the development of H5N1 attenuated vaccine by reverse genetic technology
      and discuss the problems on the vaccine production to be dissolved before
      pandemic occur.

PMID- 17037361
TI  - [DNA vaccination].
AB  - No one knows the timing when influenza pandemic will occur, but that catastrophe
      will undoubtedly happen. Current vaccines elicit antibodies to membranes of
      viruses effective against highly specific strains, however they are not effective
      against multiple strains. New strategies are urgently needed for the protection
      against multiple strains. It is necessary to develop immunologically superior
      vaccines. DNA vaccination is an established immunization method in animal models.
      DNA vaccines are gaining importance due to the induction of a strong cellular
      immunity. Moreover, the protection against multiple strains of influenza A virus
      has already been achieved. But their immunogenicity is not so strong that to
      improve the efficacy of this method is very important. This article highlights
      some of the recent developments in investigational DNA vaccines. Various tactics
      for enhancement of their immunity are considered. DNA vaccines together with DNA
      encoding various cytokines showed better immunological responses in several
      animal models. Alteration in the vector, inclusion of CpG-ODN motifs, addition of
      transcriptional factor and appropriate vaccine delivery mechanisms are expected
      to further improve the efficacy of these vaccines.

PMID- 17037362
TI  - [Intranasal inactivated influenza vaccine].
AB  - Natural influenza virus infection is well known to be superior to parenteral
      inactivated vaccines, which induce serum IgG antibodies(Abs) alone, in inducing
      the broad-spectrum cross-protection against variant virus infection. Secretory
      IgA Abs, which provide cross-protection strongly against infection with variant
      viruses within the same subtype mainly in the upper respiratory tract, serum IgG
      Abs, which provide cross-protection weakly against infection with variant viruses
      mainly in the lower respiratory tract, and cytotoxic T lymphocytes, which provide
      cross-protection against infection with different subtype viruses and whose role
      is not always big in humans, are involved in the defence mechanisms induced by
      natural infection. The development of intranasal inactivated vaccine, capable of
      inducing both IgA and IgG Abs, is important to improve the efficacy of current
      inactivated vaccine.

PMID- 17037363
TI  - [Analysis of SNPs and enzymatic disorder in the patients of influenza-associated
      encephalopathy: disorder of fatty acid metabolism in mitochondria induced by high
      fever].
AB  - To assess the etiology of influenza-associated encephalopathy(IAE), a
      surveillance effort was conducted during 2000-2005 in Japan. Over half of fatal
      and handicapped IAE patients exhibited a disorder of mitochondrial beta-oxidation
      and ATP generation evoked by the thermolabile phenotype of carnitine
      palmitoyltransferase II variations with transiently elevated serum acylcarnitine
      during high-grade fever. Model mice having impaired mitochondrial beta-oxidation
      exhibited significant accumulation of mini-plasmin and up-regulation of trypsin
      in the cerebral capillaries after infection with influenza A virus, resulting in
      the destruction of blood-brain barrier and increased brain vascular permeability.
      Trypsin up-regulation was also evident in the neuronal cells in the hippocampus,
      suggesting a severe neurologic complication of IAE.

PMID- 17037365
TI  - [Guideline for the management of influenza associated encephalopathy].

PMID- 17037364
TI  - [Neuroradiological findings in the acute stage of influenza encephalopathy].
AB  - Influenza encephalopathy(IE) is characterized by its high incidence in Japanese
      children between 1 year and 5 years of age, its onset in the first or the second
      day of illness and its high mortality (15-30%) and morbidity (25-40%). We
      proposed the classification of IE with poor prognosis from the neuroradiological
      findings. Four types of encephalopathy seem to be differentiated from each other,
      1. acute necrotising encephalopathy(ANE) type, 2. hemorrhagic shock and
      encephalopathy syndrome (HSES) type, 3. acute brain swelling(ABS) type, 4. acute
      encephalopathy with febrile convulsive status epilepticus (AEFCSE) type. The
      notable radiological features are thalamic lesions in ANE, diffuse cerebral
      cortical cytotoxic edema in HSES, reversible cerebral swelling in ABS which
      sometimes reaches lethal brain herniation, and localised cerebral edema which is
      called as "lobar edema" because its extent seems to be equivalent to cerebral
      lobes. "Lobar edema" is developed about four days after status epilepticus
      simultaneously with the onset of repetitious focal seizure and neurological
      deterioration. The radiological changes in the early phase of IE are described in
      each types. In conclusion IE is a constellation of different types of
      encephalopathy although a further research of encephalopathy is urgently needed.

PMID- 17037366
TI  - [Pneumonia associated with influenza virus infection].
AB  - The history of influenza pandemics was reviewed and clinical manifestations of
      pneumonia associated with influenza virus infections are described and several
      typical cases are presented. Several types of pneumonia associated with the
      influenza virus infection have been reported: 1) influenza complicated by
      secondary bacterial pneumonia, 2) primary influenza virus pneumonia, 3) combined
      influenza virus and bacterial pneumonia. Secondary bacterial pneumonia often
      produces a syndrome that is clinically distinguishable from that of primary viral
      pneumonia. In primary influenza virus pneumonia, chest roentgenography revealed
      bilateral infiltrations but no consolidation. Histologically, diffuse alveolar
      damage and hemorrhagic bronchiolitis were frequently observed in primary
      influenza virus pneumonia, in which case the prognosis was the worst. Although
      rare, the possibility of cryptogenic organizing pneumonia associated with
      influenza virus infection should be recognized. H. influenzae, S. pneumoniae, or
      S. aureus were frequently associated with influenza viral infection, and
      treatment against these bacteria should be considered.

PMID- 17037367
TI  - [Influenza myocarditis and pericarditis].
AB  - The true incidence of influenza myocarditis in the general population is unknown,
      because of the variable clinical presentation and the absence of a established
      noninvasive diagnostic test that can confirm the diagnosis. Influenza is,
      however, one of the frequently implicated viruses caused myocarditis as well as
      Coxsackie B, adenovirus, echovirus and cytomegalovirus. The clinical
      manifestations of viral myocarditis vary greatly from asymptomatic
      electrocardiographic changes to fulminant heart failure with fatal arrhythmias.
      We should recognize that subtle cardiac symptoms and signs in many subclinical
      cases may be overshadowed by systemic manifestations of the underlying influenza
      infection. Although specific therapy consisted of anti-viral agents, intravenous
      gamma-globulin treatment or mechanical ventricular supports may be available for
      influenza myocarditis, it has not been established that the myocarditic process
      itself will be favorably affected.

PMID- 17037368
TI  - [Acute myositis associated with influenza].
AB  - Benign acute myositis associated with influenza is reported from all over the
      world. The characteristics of this disorder is calf pain and difficulty walking
      during a viral illness (3-8 days) and creatine kinase levels are mildly or
      moderately elevated. Recovery occurred within 1 week. Midchildhood (mean age: 6-8
      years) is most commonly affected and boys are more commonly than girls and its
      ratio is 2.4 : 1 by Shimizu in Japan (1993). Elderly patients are also reported.
      Viral studies show that influenza B is more commonly than influenza A and the
      ratio is 6 : 1 by Hu in Taiwan (2004), 2.4 : 1 by Shimizu in Japan (1993). Muscle
      histology revealed isolated segmental muscle degeneration and necrosis without
      frank myositis. A direct role of influenza virus in its genesis is not clear. An
      age-related response and occurrence primarily on boys may reflect a genetic
      predisposition.

PMID- 17037369
TI  - [Influenza in the patient of chronic respiratory disease].
AB  - The patient of chronic respiratory disease belongs to high risk group of the
      influenza, and when influenza will happen, they will become sever. Therefore,
      these patient should take the vaccination at first. Being vaccinated, even if the
      influenza will occur, the condition will not be sever and with the antiviral
      agents, anti-bacterial agents should be given with or without the existence of
      bacterial infection.

PMID- 17037370
TI  - [Influenza complicating pregnancy].
AB  - Influenza is a highly contagious acute respiratory infection that is of major
      clinical importance both in Japan and worldwide. This infection usually is not
      life-threatening in otherwise healthy adults, but pregnant women do not tolerate
      serious pulmonary involvement. In previous reports of influenza pandemics,
      pregnant women have experienced increased risk of morbidity and mortality
      compared to non-pregnant women. In addition, mothers with severe respiratory
      infections may have an increased risk of preterm labor. Vaccination against
      influenza is recommended for all women who will be pregnant during the influenza
      season to prevent the occurrence of influenza and the development of pneumonia.
      There is no firm evidence that maternal infection is associated with an increased
      risk of spontaneous abortion, stillbirth, or congenital anomalies. However, an
      infant delivered to an acutely infected patient may develop neonatal influenza as
      a result of close personal contact with its mother.

PMID- 17037371
TI  - [Highly pathogenic avian influenza--monitoring of migratory waterfowl].
AB  - Since 1979, the group belonging to Departments of Veterinary Microbiology,
      Veterinary Public Health and the Avian Zoonoses Research Centre, Faculty of
      Agriculture, Tottori University is continuing isolation of avian influenza virus
      from such migratory waterfowls as whistling swan, pintail and tufted dugs flying
      from Siberia and/or northern China. They have already isolated many interesting
      influenza viruses. Serotype of the isolates is various; some H5 and H7 and human
      types of viruses were also isolated; and its pathogenicity for chickens is not
      high. It was interested that low pathogenic H5N3 virus isolated from whistling
      swan acquired severe pathogenicity during passage in chicks.

PMID- 17037372
TI  - [Type C influenza].
AB  - The influenza C virus genome consists of seven single-stranded RNA segments of
      negative polarity. The hemagglutinin-esterase (HE) glycoprotein of influenza C
      virus has three biological activities, i.e. receptor-binding activity for N
      acetyl-9-O-acetylneuraminic acid, fusion activity, and receptor-destroying
      activity, which is a neuraminate-O-acetylesterase. Unspliced mRNA from RNA
      segment 6 is first translated into a 374-amino-acid protein, P42. P42 is cleaved
      by signal peptidase, producing M1' and CM2 proteins, composed of the N-terminal
      259 amino acids and the C-terminal 115 amino acids, respectively. Xenopus laevis
      oocytes expressing influenza C virus CM2 protein demonstrated that CM2 protein
      forms a voltage-activated ion channel permeable to chloride ion.

PMID- 17037373
TI  - [Global influenza surveillance].
AB  - Global influenza surveillance is run by WHO Global Influenza Programme in
      collaboration with WHO Global Influenza Surveillance Network. Network partners
      collect specimens in their countries, perform primary virus isolation and
      preliminary antigenic characterization. They ship newly isolated strains to WHO
      Collaboration Centers for high level antigenic and genetic analysis, the result
      of which forms the basis for WHO recommendations on the composition of influenza
      vaccine for the Northern and Southern Hemisphere each year. The WHO Influenza
      Surveillance Network serves also as a global alert mechanism for the emergence of
      influenza viruses with pandemic potential.

PMID- 17037374
TI  - [Regulation of adipose functions by molecular clocks].
AB  - Adipocytes play essential metabolic roles, not only serving as massive energy
      reserves but also secreting hormones and cytokines that regulate metabolic
      activities. The link between metabolic activity in adipocytes and circadian
      rhythm has long been studied, e.g., glucose and lipid homeostasis are well known
      to exhibit circadian variation. Therefore, molecular clock may play important
      roles in regulation of metabolic activity in adipocytes. In a previous study, we
      reported that white adipose tissue contains functional molecular clock and
      expression of several adipocytokines including leptin and plasminogen activator
      inhibitor-1 displays circadian rhythm. The diurnal rhythm in the level of these
      molecules suggests that molecular clock is, at least partly, associated with the
      onset of metabolic syndrome.

PMID- 17037375
TI  - [Postoperative adjuvant therapy for premenopausal patients with breast cancer].
AB  - The age peak of breast cancer morbidity is younger in Japan in comparison with
      that in Western countries. This results in a higher incidence of premenopausal
      patients in Japan. There are specific concerns on the postoperative adjuvant
      therapy for premenopausal patients, such as its influences on pregnancy, delivery
      and lactation, and acute and chronic adverse events related to earlier ovarian
      dysfunction. International guidelines such as the recommendations by the St.
      Gallen consensus conference provide clinicians with useful information on the
      risk assessment for recurrence and treatment selection of postoperative adjuvant
      therapy. Recommendations on postoperative adjuvant therapy for premenopausal
      breast cancer patients are presented according to the guidelines and evidence
      established by clinical trials. On-going clinical trials to resolve unanswered
      questions on the adjuvant therapy are also reviewed. Finally, future perspectives
      on the adjuvant therapy are discussed.

PMID- 17037377
TI  - [Basic evaluation for new antimicrobial susceptibility testing of Mycobacterium
      leprae by bioluminescence assay (ATP method)].
AB  - Antimicrobial susceptibility testing of Mycobacterium leprae by non-radioactive
      bioluminescence assay was developed. Optimization of the assay conditions such as
      temperature and time for ATP extraction, bacteria dose, preparation of bacteria
      suspension and pH of culture medium was carried out using M. leprae Thai 53
      strain. Samples of bacterial suspension of M. leprae were first treated with
      filamentous cell treatment reagent at room temperature for 30 minutes and ATP was
      extracted from the leprosy bacilli by heating at 60 degrees for five minutes.
      Luciferin luciferase was added to the extract after cooling to room temperature
      followed by measurement of relative light units (RLU) of each sample using a
      luminometer. The concentrations of the drugs used for the evaluation of
      antimicrobial activities of rifampin (RFP), clofazimine (CLF), ofloxacin (OFLX)
      and clarithromycin (CAM) were 0.125, 0.50, 2.0 and 8.0 microg/ml respectively.
      Middlebrook 7H9 broth medium was used (pH6.6) as the basal medium and the bacilli
      were cultivated at 32 C for 0-14 days. ATP was extracted from 0.1 ml of culture
      suspension and inhibition of the luminescent activity was calculated. The results
      were compared to that obtained by radio-active CO2 detection system, Buddemeyer
      method which is commonly used for measuring anti-M. leprae activity. There was a
      good correlation between the results obtained by ATP method on the tenth day of
      culture and the results obtained by Buddemeyer method on the seventh day of
      culture. ATP method may be useful for the determination of drug susceptibility
      ofM. leprae.

PMID- 17037376
TI  - [Guideline for the treatment of Hansen's disease in Japan (Second edition)].
AB  - ad hoc committee of Japanese Leprosy Association recommends revised standard
      treatment protocol of leprosy in Japan, which is a modification of World Health
      Organization's multidrug therapy (WHO/MDT, 1997). For paucibacillary (PB)
      leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough.
      However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment
      seems insufficient. Thus, (A) For MB with bacterial index (BI) > or = 3 before
      treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is
      necessary. When BI become negative and active lesion is lost within 2 years, no
      maintenance therapy is necessary. When BI is still positive, one year of MDT/MB
      is added (3 years in total), followed by maintenance therapy by dapsone and
      clofazimine until BI negativity and loss of active lesions. (B) For MB with BI <
      3 or fresh MB (less than 6 months after the onset of the disease) with BI > or =
      3, 1 year treatment by MDT/MB is necessary. When BI become negative and active
      lesion is lost within one year, no maintenance therapy is necessary. When BI is
      still positive or active lesion is remaining, additional therapy with MDT/MB for
      one more year is recommended. This is a simplification of first version in 2000.
      Brief summary of diagnosis, purpose of therapy, character of drugs, and
      prevention of deformity is also described.

PMID- 17037378
TI  - [Leprosy services following elimination in WPRO and SEARO regions].
AB  - The elimination of leprosy with the advent of multidrug therapy (MDT) is one of
      the success stories in public health. Elimination will be achieved in the regions
      of Western pacific and South-East Asia in near future. A biregional consultation
      between the WHO South-East Asia and Western Pacific regions was held in the end
      of 2004 in Manila, the Philippines. A strategy document was developed during the
      consultation, to sustain quality leprosy services in Asia and the Pacific beyond
      2005, and to further reduce the leprosy burden. The main strategy involves timely
      detection of new cases, multidrug treatment, and the key element of integration
      of leprosy services into general health services.

PMID- 17037379
TI  - [Recent condition of new leprosy patients in Japan].
AB  - Most of 148 newly registered leprosy patients in the past 10 years from 1995 to
      2004 in Japan had received some examinations, such as histopathology test (85%),
      skin smear test (84%), estimation of PGL-I antibody titer (55%) or detection M.
      leprae with PCR method (41%). 17% of newly patients should receive wrong therapy,
      if they had not had aforesaid clinical examinations in addition to count skin
      lesions. Improvement of technical level at skin smear test should be required for
      accurate treatment program in Japan. In Japanese patients, the number has been
      decreasing year by year; epidemiological condition was different between in
      Okinawa prefecture and in others, about ratio of sex, kind of type and age group.

PMID- 17037380
TI  - Leprosy situation in Brazil.
AB  - We present the situation of leprosy in Brazil, reporting about epidemiology,
      clinical criteria for classification, multidrugtherapy and special situations, as
      co-infection. This material was presented in the 79th Annual Meeting of Japanese
      Hansen's Disease Association in May 2006, during a discussion about the Japanese
      Guidelines for leprosy treatment.

PMID- 17037381
TI  - [Current practice of genetic diagnosis for Mycobacterium leprae].
AB  - Laboratory tests necessary for the diagnosis of leprosy have not been well
      introduced in general hospitals and clinical laboratories. Therefore, several
      tests have been performed in Leprosy Research Center, National Institute of
      Infectious Diseases since July, 1997, as a part of administrative examinations
      (tests done by request of Ministry of Health, Labour and Welfare). These
      examinations include histopathology, serum antibody titers (anti-PGL-I antibody),
      PCR test and bioactivity of anti-bacterial agents.

PMID- 17037382
TI  - [Development of rapid and simple genomic diagnostic method].
AB  - To develop the rapid and simple genomic diagnostic method, we analyzed the
      partial dnaA sequence of 27 mycobacterial species. The partial dnaA sequence
      could distinguish M. kansasii and M. gastri. Based on this region and RLEP
      sequence of M. leprae, we established the loop-mediated isothermal amplification
      method (LAMP) to detect each species. The LAMP method for M. kansasii and M.
      gastri, could detect 500 copies. Five copies of M. leprae genomic DNA could be
      detect in 30min. To simplify the sample processing, the LAMP assay was performed
      with FTA filter paper. M. leprae bacilli were applied on filter paper that lyses
      bacilli and bound DNA, eliminating sample centrifugation and extraction
      procedures. Assays of number standards showed reproducible detection rate 50
      bacilli of M. leprae. Thus, The LAMP assay combined with FTA card has the
      advantages of rapid and simple detection and provides a practical, economical,
      and specific method for the diagnosis of M. leprae and NTM infection.

PMID- 17037384
TI  - [Identification of an immunodominant antigen of Mycobacterium leprae and its
      application for the development of protective measures].
AB  - Host defense against Mycobacterium leprae (M. leprae) is chiefly conducted by
      cellular immunity. The adaptive immunity plays an important role, and T cells are
      activated through recognition of some immunodominant antigens of M. leprae. A
      search for an immunodominant antigen was carried out using human peripheral
      monocytes-derived dendritic cells and M. leprae-derived cell membrane fraction
      which is the most antigenic fraction of the bacteria, and Major Membrane Protein
      (MMP)-II was found as one of the immunodoninant antigens. The MMP-II highly
      stimulated both dendritic cells and macrophages to produce various cytokines.
      Further, MMP-II was recognized by T cells in vivo in patients infected with M.
      leprae. Then, we constructed a recombinant BCG secreting MMP-II. The recombinant
      BCG strongly stimulated both naive CD4+ and naive CD8+ T cells, and seemed to be
      a useful immunostimulatory agent.

PMID- 17037383
TI  - [DNA microarray based rapid drug susceptibility test for Mycobacterium leprae].
AB  - Antibiotic susceptibility test of Mycobacterium leprae still relies on the time
      consuming methods based on the growth of M. leprae in the mouse footpad. Thus,
      the establishment of a rapid, simple and reliable method for the detection of
      drug-resistant M. leprae is one of the most urgent subjects in the treatment of
      leprosy patients. Recently, many data on the mutation of specific genes
      correlating with drug resistance have been accumulated. Application of these data
      permit the establishment of new gene diagnostic methods for drug susceptibility
      test of leprosy. In this paper, the method using the low density oligonucleotide
      array that enables the detection of base substitutions involved in resistance
      against anti-leprosy drugs on a single platform was discussed. The low density
      oligonucleotide array described in this paper will open the new perspectives in
      terms of patient management for leprosy with low cost requirement.

PMID- 17037385
TI  - Diagnosis of leprosy: serological aspects.
AB  - The most convenient way of diagnosing an infectious disease is by serological
      methods. To improve the quality of diagnosis in leprosy, simple tests in addition
      to diagnosis by clinical signs, are necessary. Here, PGL-I based methods for
      detection of multibacillary and paucibacillary leprosy, have been revisited and
      newer methods are discussed.

PMID- 17037386
TI  - [Present situation of falling accidents in leprosy hospitals].

PMID- 17037387
TI  - [Identification of mycobacteria by sequencing of rpoB gene and 16S rRNA].
AB  - PURPOSE: To classify a specific Mycobacterium among various mycobacteria
      utilizing sequencing of rpoB gene. To classify mycobacteria not identified by DNA
      DNA hybridization (DDH) using sequencing of rpoB and 16S rRNA gene. OBJECTS AND
      METHODS: Classification of 106 Mycobacteria strains, one Nocardia strain, one
      Rhodococcus strain, four Gordona strains was made by using partial sequencing of
      rpoB and 16S rRNA (RIDOM). Thereafter, 38 mycobacteria clinical strains not
      identified by DDH were classified utilizing the DNA sequencing data. RESULTS:
      Pairs of M. kansasii and M. gastri, M. abscessus and M. chelonae, M.fortuitum
      (ATCC49404) and M. polcinum, M. peregrinum and M. septicum, M. farucinogense and
      M. senegalense and M. fortuitum (ATCC49403), Rhodococcus, Nocardia and Gordona
      strains were classified using sequencing of rpoB gene. Even though sequencing of
      rpoB and 16S rRNA gene was utilized, it was impossible to classify M.
      tuberculosis complex, M. avium family, M. marinum and M. ulcerans, and M.
      fortitum subsp. fortuitum and M. fortuitum subsp. acetamidolyticus. The 38
      mycobacteria clinical strains not identified by DDH were successfully classified
      using sequencing of both rpoB and 16S rRNA. These sequencing analyses showed that
      M. heckeshornense, M. branderi, M. intermedium, M. shimoidei, M. wolinskyi, M.
      malmoense and M. lentiflavum could be identified. Thirty six clinical isolates
      (94.7%) and 32 clinical isolates (84.2%) were identified by rpoB sequencing and
      16S rRNA sequencing (RIDOM), respectively. CONCLUSION: The classification ratio
      of mycobacteria including Nocardia, Rhodococcus and Gordona is 69.6% for
      sequencing of 16S rRNA and 89.3% for sequencing of rpoB gene. Sequencing of rpoB
      is useful for classification of mycobacteria due to its genetic diversity, but
      has some limitation in its application. In order to classify mycobacteria more
      accurately, it is important to combine sequencing of rpoB and 16S rRNA and
      biochemical/biological tests.

PMID- 17037388
TI  - [Usefulness of variable numbers of tandem repeats typing in clinical strains of
      Mycobacterium avium].
AB  - OBJECTIVES: We evaluated the usefulness of Variable Numbers of Tandem Repeats
      (VNTR) analysis, which was recently reported as a new typing method of
      Mycobacterium avium strains of animal origin, for strain differentiation of
      clinical isolates of M. avium in comparison with the standard IS1245-RFLP typing
      method. In addition, forty M. avium isolates recovered from sputum samples of
      same patient in different times were analyzed with VNTR typing method. SUBJECTS
      AND METHODS: The subjects were twenty-four clinical isolates of M. avium stocked
      at Higashi Nagoya National Hospital and discriminatory power was evaluated with
      Hunter Gaston Discriminatory Index (HGDI). Furthermore, forty M. avium isolates
      recovered from sputum samples of one patient obtained at four different times
      were analyzed by using this VNTR typing method. RESULTS: VNTR typing showed
      better discriminatory power for twenty-four clinical isolates than IS1245-RFLP
      method (HGDI: 0.975 vs 0.866). In the second study, polyclonal infection of four
      genotype strains with different allele profiles were detected. The ratio of
      mixture of the four different genotype strains varied during clinical course.
      CONCLUSION: We considered that VNTR typing method was very useful for
      discriminatory examination of M. avium.

PMID- 17037389
TI  - [Influence of aging on tuberculosis infection--an epidemiological study of 1,141
      smear-positive TB patients].
AB  - OBJECTIVES: To elucidate the influences of aging on the tuberculosis infection.
      SUBJECTS AND METHODS: The subjects of this retrospective study were 1,141 smear
      positive pulmonary tuberculosis (TB) patients registered in Aichi prefecture
      between 1989 and 2003. All registration files were reviewed to identify
      epidemiological links of patients. When linked patients with an interval of the
      dates of registration of less than 10 years were found, the earliest case was
      considered as the source case, and the other patients were regarded as secondary
      cases. An epidemic source rate (ESR) for a category of patients (e.g., age-group,
      etc.) was defined as following; ESR= NS/NA X 100, where NA: Number of smear
      positive pulmonary TB patients in a category A, and NS: Number of source cases in
      category A. RESULTS: A total of 70 source cases were identifed and the ESR was
      6.1%. The ESRs for different age-groups were; 14.3 % for 10-19 years of age (NA =
      14), 13.5% for 20-29 years (NA = 74), 14.6% for 30-39 years (NA = 48), 15.0% for
      40-49 years (NA = 107), 6.9% for 50-59 years (NA = 145), 3.5% for 60-69 years (NA
      = 227), 3.8% for 70-79 years (NA = 293), 2.8% for 80-89 years (NA = 212), and 0%
      for 90-99 years (NA = 21). The ESR were significantly different between those
      aged 40 to 49 years and those aged 50 to 59 (p<0.05). The ESR was significantly
      different between those aged 59 years and younger and those aged 60 years or
      older (11.6% vs 3.3%, p<0.001). The ESR was significantly different between those
      patients with cavitary lesion and those with noncavitary lesion in the younger
      groups (14.3% vs 5.2%, p<0.01), as well as in the elder age-groups (4.8% vs 1.7%,
      p<0.01). The rate in the younger groups was 6.3% for those with lower smear
      positivity (Gaffky 1 to 4), compared with 15.3% for those with intermediate smear
      positivitiy (Gaffky 5 to 8), and 32.4% for those with higher smear-positivity
      (Gaffky 9 and 10) (with p<0.01, p<0.05 respectively), while the rates were 3.1%,
      3.9%, and 3.4%, respectively in the older groups. CONCLUSION: These findings
      suggest that the infectivity is significantly lower in older groups.

PMID- 17037390
TI  - [Comparison between direct smear by Ziehl-Neelsen and concentrated smear by
      fluorochrome stain].
AB  - PURPOSE: For the purpose of supporting more completely our assertion that two
      times concentrated sputum smear tests by fluorochrome stain are more sensitive
      than or at least equal to 3 times direct smear tests by Ziehl-Neelsen stain, we
      compare the sensitivity of concentrated smear by stain (conc-smear) and direct
      smear by Ziehl-Neelsen stain (di-smear). OBJECT AND METHOD: Retrospective study
      of sputum acid-fast smear tests in our hospital with tuberculosis ward from Jan.
      1, 2003 to Sep. 30, 2005. RESULT: 170 of 899 sputums on which both conc-smear and
      di-smear were done, were smear positive by at least one of the two smear method.
      Of those 170, 167 (98.2%) were positive by conc-smear and 113 (66.5%) were
      positive by di-smear, and the difference was statistically significant (p<0.001).
      Of those 110 that were positive by both conc-smear and di-smear, in 65 (59.1%)
      smear grade by conc-smear were higher than that of di-smear, and in 3 (2.7%)
      smear grade by di-smear were higher than that of conc-smear. Smear grades in conc
      smear were significantly higher than that of di-smear (p< 0.001). CONCLUSION: In
      sensitivity and smear grades, conc-smear was superior to di-smear. Together with
      previous report, 2 times conc-smear tests are supposed to be superior to 3 times
      di-smear.

PMID- 17037391
TI  - [A case of lung tuberculosis showing no chest radiograph findings with recurrent
      hemoptysis].
AB  - A 59-year-old male was referred to our hospital because of hemoptysis. A chest X
      ray film and 7 mm-slice CT scan showed no abnormal finding. Bronchoscopy revealed
      hemorrhage in the right upper bronchus (B1a) Bronchial lavage of the lesion was
      performed, but Mycobacterium tuberculosis was not detected. Because of repeated
      hemoptysis, he was admitted to our hospital. Right bronchial artery angiograph
      showed vascular hyperplasia in the peripheral part of the upper lobal branch, and
      this lesion was suggested to be a bleeding point. There were no vascular
      malformations. Thin slice (0.5 mm-thick) CT scan showed mild infiltrative shadow
      in the right upper lobe. After admission, sputa smear for mycobacteria and PCR
      for M. tuberculosis became positive, and he was diagnosed as pulmonary
      tuberculosis. After starting antituberculous chemotherapy, hemoptysis
      disappeared, and sputa smear and culture for mycobacteria converted to negative.
      This case suggests that lung tuberculosis should be suspected in patients having
      hemoptysis, even though they had no chest X-ray film abnormality.

PMID- 17037392
TI  - [Chlamydia pneumoniae infections].
AB  - Chlamydia pneumoniae, an obligate intracellular human pathogen, causes infections
      of the respiratory tract. It is a significant cause of both lower and upper acute
      respiratory illnesses, including pneumonia, bronchitis, pharyngitis and
      sinusitis. Most respiratory infections caused by C. pneumoniae are mild or
      asymptomatic. Some studies have suggested a possible association of C. pneumoniae
      infection and acute exacerbations of asthma and chronic obstructive pulmonary
      disease (COPD). Seroepidemiological studies showing antibody prevalence rates in
      a range of 50 to 70% suggest that C. pneumoniae is widely distributed and that
      nearly everybody is infected with the agent at some time. C. pneumoniae can cause
      prolonged or chronic infections which may be due to persistence for months or
      years. These persistent infections have been implicated in the development of a
      number of chronic diseases including atherosclerosis, asthma and COPD. These
      persistent chlamydial infections can be established in vitro using several
      methods including cytokines, antibiotics and deprivation of certain nutrients.
      Despite differences in treatment, chlamydiae respond to form inclusions
      containing atypical reticulate bodies (RBs), which occasionally have been shown
      to be pleomorphic forms, termed aberrant form (AF). The AF is generally larger in
      diameter than typical RBs, and display a sparse densinometric appearance. In
      general, it is likely that this aberrant developmental step leads to the
      persistence of viable but nonculturable chlamydiae within infected cells over
      long periods. Removal of several stress factors described above results in the
      condensation of nuclei, the appearance of late proteins, and the production of
      viable, infectious elementary bodies (EBs). Most of the major sequelae of
      chlamydial disease are thought to arise from either repeated or persistent
      chlamydial infection of an individual. The persistence would allow constant
      presentation to the individual immune response of these potentially deleterious
      immune targets. Since repeated infection can certainly be documented in many
      clinical settings, persistence is thought to also play a role.

PMID- 17037393
TI  - Establishment of a clinical pathway as an effective tool to reduce
      hospitalization and charges after video-assisted thoracoscopic pulmonary
      resection.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of establishing a
      clinical pathway based on the length of hospitalization, hospital charges, and
      the outcome for video-assisted thoracoscopic pulmonary resection (VATPR).
      METHODS: We retrospectively analyzed consecutive patients who were diagnosed as
      having primary lung cancer, metastatic lung cancer, or a nodule that was
      suspected to be malignant and thus was operated on using VATPR during the 1-year
      period before (n = 105) and after (n = 113) pathway implementation. RESULTS: The
      mean economic cost and total hospital stay before and after pathway
      implementation were about dollars 14439 and dollars 13093 (US), and 29.4 and 18.6
      days, respectively. These figures were significantly lower after pathway
      implementation than before establishment of the pathway. CONCLUSION: A clinical
      pathway is thus considered useful for reducing the length of total hospital stay
      and the costs associated with VATPR while maintaining high-quality postoperative
      care.

PMID- 17037394
TI  - Comparison of surgical outcome using the prediction scoring system of E-PASS for
      thoracic surgery.
AB  - OBJECTIVE: The purpose of this study was to determine if our predictive scoring
      system, E-PASS, can estimate the surgical outcome. METHODS: We conducted a
      multicenter cohort study for 3 years in four national hospitals. A consecutive
      series of 731 patients who underwent elective thoracic operations were analyzed.
      The preoperative risk score (PRS) and the comprehensive risk score (CRS) of the E
      PASS were determined preoperatively and immediately after the operation,
      respectively. The cost of the surgical admission and the severity of the
      postoperative complications were recorded at the time of discharge. RESULTS: The
      CRS significantly correlated with the severity of the postoperative complications
      (rs = 0.728, P < 0.0001) and the charge (rs = 0.530, P< 0.0001). When the
      estimated/real morbidity ratio (MR) among the hospitals was compared, it varied
      from 0.16 to 0.59. A significant increase in the cost was observed according to
      the CRS. CONCLUSION: The E-PASS scoring system may be useful for standardizing
      the patient population and surgical severity to compare the surgical outcome.

PMID- 17037395
TI  - Primary malignant melanoma: a rare cause of mediastinal mass.
AB  - A case of primary malignant melanoma in the mediastinum presenting as recurrent
      laryngeal nerve palsy is reported. Tissue biopsy at mediastinotomy yielded a
      diagnosis of malignant melanoma. The mass was fixed to the left aspect of the
      trachea and to the upper border of the left main bronchus and could not be
      removed surgically. Further extensive clinical and radiological investigations
      revealed no evidence of tumor elsewhere in the body.

PMID- 17037396
TI  - Nodular pulmonary amyloidosis.
AB  - A 72-year-old woman with a diagnosis of suspected rheumatoid arthritis was
      admitted with multiple pulmonary nodules in the bilateral lung field. To obtain a
      diagnosis, a nodule was resected using video-assisted thoracic surgery.
      Microscopically, amorphous eosinophilic acellular substances were surrounded by
      inflammatory infiltrates, which were confirmed to be amyloid deposits by congo
      red staining. Thus, a diagnosis of pulmonary amyloidosis was obtained. The
      clinical features and diagnostic process are discussed.

PMID- 17037397
TI  - Chest wall defect and chronic pleural infection: surgical treatment with
      thoracomyoplasty and open window thoracostomy.
AB  - We report a rare case of a 75-year-old hemiplegic man with a chronic pleural
      infection, a bronchopleural fistula, and a full-thickness defect of the chest. In
      one operation we performed open-window thoracostomy and pleural decortication as
      well as reconstruction of the chest defect and reclosure of the bronchopleural
      fistula with a latissimus dorsi muscle flap. The patient made a good recovery and
      was sent for rehabilitation in good condition. Surgical treatment was essential
      to control and ultimately halt the septic process. Use of a muscle transplant in
      a hemiplegic patient did not reduce mobility.

PMID- 17037398
TI  - Giant cell tumor of the sternum.
AB  - A primary giant cell tumor (GCT) originating from the sternum is extremely rare.
      We report a case of a GCT originating from the sternum in a 45-year-old man who
      was referred to us for a mass in the anterior chest wall that had been growing
      slowly. Computed tomography revealed a soft tissue mass involving a large
      osteolytic and destructive lesion of the sternum body. Subtotal sternectomy and
      reconstruction with methylmethacrylate were performed. The tumor was 8.5 x 4.5 x
      2.5cm, and the histopathological examination confirmed GCT. Radical wide
      resection of primary sternum tumors and reconstruction with an appropriately
      rigid prosthetic material are necessary to minimize local recurrence.

PMID- 17037399
TI  - Compromised video-assisted thoracoscopic segmental resection for high-risk
      patients with stage I lung cancer near the lung hilum.
AB  - We performed a video-assisted thoracoscopic segmental resection without doing a
      mini-thoracotomy in two patients (one octogenarian and one with poor lung
      function) with early stage (T1-2N0) lung cancer located at the lung hilum who
      required preservation of their cardiopulmonary function. After 2 years of follow
      up, both patients are alive without recurrence. We describe the cases and the
      method used for the video-assisted thoracoscopic segmental resection using an
      endoscopic stapler.

PMID- 17037400
TI  - Simultaneously performed mitral valve replacement and Hartmann's operation for
      infectious endocarditis from Streptococcus bovis and rectal cancer.
AB  - In patients with surgical indications for both cardiac surgery and a malignant
      neoplasm, cardiac surgery should generally be performed first; however, in some
      cases simultaneous surgery is recommended. We report a case of infectious
      endocarditis of the mitral valve caused by Streptococcus bovis with rectal
      cancer. Blood cultures showed a rise in coagulase-negative S. bovis, and the
      source of infection was thought to be the rectal cancer. The patient presented
      with cerebral infarction prior to surgery, and the possibility of recurrence of
      an infarction was predicted. The tumor of the rectum was hemorrhagic, so to avoid
      hemorrhagic complications due to perioperative heparinization and anticoagulant
      therapy and to remove the source of infection, mitral valve replacement and a
      Hartmann's operation were performed simultaneously. The postoperative course was
      uneventful.

PMID- 17037401
TI  - Primary pulmonary sarcomatoid carcinoma with intracardiac extension.
AB  - Primary pulmonary sarcomatoid carcinoma is rare. It is generally regarded as an
      aggressive tumor. We report, to our best knowledge, the first case of pulmonary
      sarcomatoid carcinoma with extensive intracardiac spread. This case illustrated
      the misleading clinical features of this condition. Previous literature is also
      reviewed.

PMID- 17037402
TI  - Clopidogrel (PLAVIX) increases risk of bleeding in a patient undergoing coronary
      artery bypass grafting.

PMID- 17037403
TI  - [Clinical study of 90 cases of Mycoplasma pneumoniae pneumonia].
AB  - We investigated 90 patients with Mycoplasma pneumoniae (M. pneumoniae) pneumonia.
      Forty-four patients were men, 46 were women and the mean age was 43.1 years old.
      Twenty-nine patients were smokers and 28 had underlying diseases. As for
      diagnostic method, 16 were culture positive, 71 had a fourfold increase in
      antibody titer to M. pneumoniae, and 3 were both culture positive and had a
      fourfold increase in antibody titer. Regarding the degree of severity, 21
      patients were classified as severe according to Japanese Respiratory Society
      diagnostic criteria, 11 patients were diagnosed as severe according to American
      Thoracic Society diagnostic criteria. Partial pressure of arterial oxygen (PaO2)
      of 18 patients were <60mmHg, 5 patients were under mechanical ventilation, and 3
      patients died. Three of 16 patients treated with only beta-lactum antibiotics
      recovered. The 3 patients who died were M. pneumoniae culture-positive and two
      patients had polymicrobial infections. Severe pneumonia associated with
      Mycoplasma pneumoniae infection is not unusual. If a rapid diagnosis kit or
      culture method of M. pneumoniae pneumonia is not introduced, the pathogen might
      be unknown in cases of rapid death due to M. pneumoniae pneumonia. These data
      suggest that the mortality rate of M. pneumoniae pneumonia might be
      underestimated without these detection tests.

PMID- 17037404
TI  - [Clinical features of Pneumocystis pneumonia in patients with systemic lupus
      erythematosus].
AB  - Systemic lupus erythematosus (SLE) is often associated with various opportunistic
      infections, particularly during treatment with corticosteroids or
      immunosuppressants. We studied the clinical characteristics of 15 patients with
      SLE who underwent diagnostic bronchoalveolar lavage (BAL) and compared 6 patients
      with confirmed Pneumocystis pneumonia (PcP+), with 9 patients without
      Pneumocystis pneumonia (PcP-). The serum concentrations of beta-D-glucan and KL-6
      were significantly higher in PcP+ than in PcP- patients, whereas serum LDH was
      similar in both groups. The serum concentrations of complement, a marker of SLE
      activity, and of IgG did not predict the presence of PcP. In all patients, the
      overall cell and lymphocyte counts were increased in the BAL fluid, without any
      significant difference between the PcP+ and PcP- groups. Ground-glass opacities
      on chest computed tomography, and oxygenation impairment (PaO2/FiO2<200Torr) were
      more common in PcP+ than PcP- patients. We concluded that, in patients with SLE,
      serum beta-D-glucan and KL-6 might be useful in the diagnosis of PcP,
      particularly when severe hypoxemia precludes BAL.

PMID- 17037405
TI  - [Gastropleural fistula due to perforated gastric ulcer].
AB  - A 65-year-old woman, who had been taking non-steroidal anti-inflammatory drugs
      (NSAIDs), prednisolone and methotrexate for rheumatiod arthritis, was admitted to
      our hospital with a sudden onset of left-back and chest pain and breathlessness.
      A chest radiograph and computed tomography revealed a left-side pneumothorax and
      pleural effusion. Chest tube was inserted for drainage and the fluid was formed
      to contain food residuum. Contrast radiography demonstrated escape of soluble
      contrast medium into the left pleural space. A thoracotomy and transdiaphragmatic
      revealed a gastropleural fistula. It was repaired and the gastric origin was
      resected. Pathologic evaluation revealed evidence of chronic peptic ulceration,
      but no malignant change. Gastropleural fistula due to peptic ulcer without
      esophageal herniation, malignancy, or traumatic injury is extremely unusual. The
      cause of the focal adhesion of the gastric ulcer and diaphragm, fistula formation
      was not certain but was probably related to the ingestion of NSAIDs in
      combination with prednisolone and other immunosuppressive agents. Although
      gastropleural fistula is rare, the prognosis in such patients related to early
      diagnosis and surgical intervention, emphasizing the importance of including this
      condition when making a differential diagnosis.

PMID- 17037406
TI  - [Identification of propionibacterium acnes in a case with stage III pulmonary
      sarcoidosis involving hepatosplenic disease].
AB  - A 35-year-old woman was admitted to our hospital because of an abnormal chest
      radiograph. Chest X-ray on admission showed multiple small nodular shadows in
      both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover,
      abdominal CT showed some nodules in the liver and spleen, and serum ACE was
      slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung
      biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary
      sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated
      non-caseating epithelioid cell granulomas with giant cells in both specimens.
      Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of
      sarcoidosis, was detected in giant cells in the lung and epitheliod cell
      granuloma of liver tissue. This case was of interest considering P. acnes might
      have been the causative pathogen.

PMID- 17037408
TI  - [A case of Heerfordt's syndrome with an elevated serum TNF alpha].
AB  - A 27-year old man who had developed uveitis, swelling of the right parotid gland,
      right facial nerve paralysis and fever, was admitted to our hospital. A chest X
      ray film showed bilateral hilar lymphadenopathy. Serum levels of angiotensin
      converting enzyme and lysozyme were elevated. Histological findings of
      transbronchial lung biopsy specimens showed non-caseous epithelioid cell
      granulomas. Therefore, sarcoidosis was diagnosed. This case also fulfilled the
      criteria for Heerfordt's syndrome. Adiministration of prednisolone (PSL)
      initially improved the patient's symptoms, but rapid tapering of PSL worsened his
      symptoms. Thus, administration of high-dose PSL for a long time was required. He
      also showed elevated levels of TNF alpha in serum.

PMID- 17037407
TI  - [A case of pulmonary adenocarcinoma accompanied by minimal change nephrotic
      syndrome, antiphospholipid syndrome and warm-type autoimmune hemolytic anemia].
AB  - A 49-year-old man was urgently admitted due to edema in both leg and left toe
      pain. A chest radiograph revealed a solitary nodule in the right lung field.
      Detailed investigations including bronchoscopy and renal biopsy led to a
      simultaneous diagnosis of clinical stage IIIB pulmonary adenocarcinoma, minimal
      change nephrotic syndrome, antiphospholipid syndrome, and warm-type autoimmune
      hemolytic anemia. Prednisolone was administered for nephrotic syndrome,
      antiphospholipid syndrome and warm-type autoimmune hemolytic anemia, and 6
      courses of chemotherapy with 70Gy radio-therapy were performed. The pulmonary
      nodule significantly decreased in size and the other three autoimmune diseases
      appeared to be well-controlled. Thirteen months after admission, multiple brain
      metastases developed along with worsening antiphospholipid syndrome symptoms
      including lupus anticoagulant. Following whole-brain irradiation, the brain
      metastases decreased in size and antiphospholipid syndrome symptoms improved.
      Thirty-nine months after the initial visit, the primary lung cancer, its brain
      metastasis and the 3 other autoimmune diseases appeared to be well-controlled.
      The temporal correlation of the lung cancer and the three autoimmune diseases
      suggests the latter may be paraneoplastic syndrome.

PMID- 17037409
TI  - [A case of successful bronchial artery embolization for primary racemose
      hemangioma with massive hemoptysis].
AB  - We encountered a case of primary racemose hemangioma treatment with successful
      bronchial artery embolism for massive hemoptysis. A 56-year-old woman with
      massive hemoptysis was transported to our hospital. The source of the massive
      hemoptysis was observed to be from around a non-pulsatile polyp covered by normal
      mucosa occluding the truncus intermedius by fiberoptic bronchoscopy. We stopped
      the bleeding temporarily using differential lung ventilation, and then bronchial
      artery angiography was performed. The main right bronchial artery was enlarged,
      and enlarged and convoluted right peripheral bronchial vessels were also
      observed. We diagnosed the massive bleeding to be due to racemose hemangioma. A
      successful bronchial artery embolization (BAE) was performed with gelforms and
      metallic coils for the treatment of racemose hemangioma. There has been no
      recurrence of hemoptysis for one year after BAE. There have been many reports on
      massive hemoptysis as in this patient who were treated by lobectomy, nevertheless
      we would like to state BAE should be considered as a suitable treatments for
      primary racemose hemangioma with hemoptysis if there is no recognizable shunt
      artery.

PMID- 17037410
TI  - [A couple suffering acute respiratory illness due to waterproofing spray
      exposure].
AB  - The patients were a 28-year-old man and a his 27-year-old wife. The husband
      smoked a cigarette immediately after using a waterproofing spray, and developed
      fever, cough, and dyspnea 15 min later. The wife had nausea 2 hours later. Nine
      hours later, the husband visited a local clinic, and was referred to our hospital
      because of hypoxemia. In addition, chest CT showed ill-defined areas of increased
      density, predominantly in the bilateral upper lung fields, with interlobular
      septal thickening, and he was hospitalized. Although the wife was asymptomatic at
      the time of examination, she had chest CT findings similar to those of her
      husband, and was also hospitalized. After admission, the husband received steroid
      pulse therapy and oxygen inhalation for his symptoms and hypoxemia, with return
      of arterial blood gas analysis results to normal on the third day. The wife had
      no symptoms or hypoxemia during her hospital stay. Their chest CT findings
      improved on the seventh day after admission, and they were discharged. Thus, it
      appears that the couple suffered from acute respiratory illness due to
      waterproofing spray exposure, and probably heat degradation products from
      cigarette smoking caused the husband to have severe symptoms.

PMID- 17037411
TI  - [Two lung adenocarcinoma patients with multiple brain metastasis treated with
      Gefitinib and surviving more than 2 years].
AB  - Case 1 is a 78-year-old woman in whom lung adenocarcinoma with multiple brain
      metastasis (cT2N3M1, stage IV) was diagnosed. She was treated with Gefitinib
      alone. Her lung tumor and metastatic brain lesions decreased 6 months after the
      start of therapy. She has no recurrence and is still alive with a good
      performance status after 25 months. Case 2 is an 80-year-old woman in whom lung
      adenocarcinoma with multiple brain (cT2N3M1, stage IV) was diagnosed. She was
      also treated with Gefitinib alone and her lung tumor and metastatic brain becomes
      improved 6 months after the start of therapy. She maintained a good performance
      status for more than 2 years (29 months). However, 29 months after beginning
      treatment, she had recurrence in bone and died 2 months later, 31 months after
      the start of therapy. The prognosis of non-small cell lung cancer with multiple
      brain metastasis is very poor and the efficacy of chemotherapy for the treatment
      of multiple brain metastases is limited, and longterm survival remains
      disappointing. We report two lung adenocarcinoma patients with multiple brain
      metastasis who survived more than 2 years by treatment with Gefitinib alone.

PMID- 17037412
TI  - [An autopsy case of Aspergillus pneumonia after inhalation of a great deal of
      dust in a mushroom factory].
AB  - A man in his forties with alcoholic liver injury was referred to our hospital
      because of progressive dyspnea and diffuse infiltrative shadows in both lung
      fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms
      in his factory, and then inhaled a great deal of airborne dust. Serological
      examination showed extremely elevated beta-D-glucan and positive Aspergillus
      antigen. Culture of dust collected from the floor of the factory proved to be
      positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and
      treatment with anti-fungal drugs was started. In spite of intensive treatment he
      died of respiratory failure. The autopsy disclosed multiple abscess formation
      containing hyphae of Aspergillus fumigatus and granulomatous reaction with
      multinuclear giant cells. However, there was no Aspergillus invasion in other
      organs. This was a rare case of invasive pulmonary aspergillosis that developed
      after inhalation of organic dust in a non-immunocompromised host.

PMID- 17037413
TI  - [A case of acute exacerbation of chronic pulmonary thromboembolism with essential
      thrombocythemia during treatment for hemoptysis].
AB  - An 89-year-old woman with essential thrombocythemia and chronic respiratory
      failure was admitted for treatment of hemoptysis. She stopped taking aspirin and
      was given tranexamic acid. Though her hemoptysis improved, respiratory failure
      suddenly worsened. As a result of various examinations and laboratory findings,
      acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though
      there was the risk of recurrence of hemoptysis, she started taking aspirin again.
      Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and
      hemorrhage are common complications of essential thrombocythemia, however,
      pulmonary thromboembolism is a rare complication. There is a possibility that the
      exacerbation of this case was caused by tranexamic acid as well as rest and
      cessation of aspirin. If a patient with essential thrombocythemia bleeds, we
      should be careful when using tranexamic acid.

PMID- 17037415
TI  - Time-based E&M coding.

PMID- 17037414
TI  - [A case of psittacosis showing a localized peripheral air-space consolidation].
AB  - A 29-year-old man was admitted with fever and anorexia. Radiographic examinations
      of the chest showed a localized peripheral non-segmental air-space consolidation
      in the right lower lobe. He had a history of exposure to parakeets, and
      psittacosis was diagnosed based on the elevated serum complement fixation titer
      against Chlamydia psittaci. The common radiographic finding of psittacosis is
      ground-glass attenuation radiating from the hilar areas. We report a rare case of
      psittacosis presenting a localized consolidation, clearly limited to the
      subpleural region of the lung.

PMID- 17037416
TI  - Getting rid of a computer? Be careful!

PMID- 17037417
TI  - Online "visits": insurers pay but docs don't play.

PMID- 17037418
TI  - ICD-9: what's new.

PMID- 17037420
TI  - In death as well as life.

PMID- 17037419
TI  - My cure for Sunday syndrome.

PMID- 17037421
TI  - The best EHRs for small practices.

PMID- 17037422
TI  - An offer he couldn't refuse.

PMID- 17037423
TI  - The doctor is out....

PMID- 17037424
TI  - Going not-for-profit saved this doctor's practice.

PMID- 17037425
TI  - "Lost chance of survival": the new malpractice risk.

PMID- 17037426
TI  - Limit liability for hospital procedures.

PMID- 17037427
TI  - ["Doing everything for planning the 2007 elections"].

PMID- 17037428
TI  - [Summer universities for an ambitious future].

PMID- 17037429
TI  - [Tattoos with henna: attention; danger!].

PMID- 17037430
TI  - [Heimlich maneuver].

PMID- 17037432
TI  - [Cardiopulmonary arrest].

PMID- 17037431
TI  - [Manual respiration using a mask].

PMID- 17037433
TI  - [Mouth-to-mouth resuscitation].

PMID- 17037434
TI  - [Gastric lavage].

PMID- 17037435
TI  - [Emergency vehicles].

PMID- 17037436
TI  - [Age-related macular degeneration].

PMID- 17037437
TI  - [Professional integration of nursing staff in oncology].

PMID- 17037438
TI  - [Swan-Ganz catheters].

PMID- 17037439
TI  - [The prerequisite of calculating the dosage].

PMID- 17037440
TI  - [Care of patients and preventing back diseases].

PMID- 17037441
TI  - [Information on anesthesiology in the operating room].

PMID- 17037442
TI  - [Adrenaline].

PMID- 17037443
TI  - [Interventional radiology].

PMID- 17037444
TI  - [Helping victims of a cerebrovascular accidents].

PMID- 17037445
TI  - The relationship of personality and behavioral development from adolescence to
      young adulthood and subsequent parenting behavior.
AB  - The purpose of the study was to examine the association of parental personality,
      behavior, and substance use during adolescence and adulthood as related to the
      later parent-offspring relationship. The sample consisted of 297 parents (M age
      32 yr.), who were first interviewed at earlier points in their lives in childhood
      and early adolescence at six points in time, extending from 1983 to 2002.
      Multiple regression models showed that parents with certain earlier personality
      and behavioral attributes, e.g., more rebelliousness and more frequent tobacco
      use, had a more difficult relationship with their children. Findings indicated an
      association between the cumulative number of psychosocial risk factors in the
      parents and difficulties in the parent-child relationship. The findings suggested
      that interventions designed to decrease youths' substance abuse may increase the
      likelihood that later when they are parents they will form nurturing
      relationships with their children.

PMID- 17037446
TI  - Attitude towards euthanasia in relation to death anxiety among a sample of 343
      nurses in India.
AB  - Scores on Attitude towards Euthanasia were correlated with scores on Death
      Anxiety among 343 female nurses in India using Templer's Death Anxiety Scale and
      the authors' 24-item attitude scale. No significant correlation was found between
      the two sets of scores (r = -.09) or a nonlinear score on relation. Age of nurses
      was not significantly related to Attitude towards Euthanasia (r = .07) or Death
      Anxiety (r = .11). As measured, death anxiety has no bearing on attitude about
      euthanasia.

PMID- 17037447
TI  - A Japanese short form of the Swanson Cognitive Processing Test to measure working
      memory: reliability, validity, and differences in scores between primary school
      children of the United States and Japan.
AB  - The purpose of this study was to examine the reliability and validity of a
      Japanese short form of the Swanson Cognitive Processing Test, which assesses
      capacity of working memory. Test-retest reliability was acceptable (r = .76).
      Concurrent validity was suggested through comparison of scores on the Reading
      Span Task (r = .55). Means on the Japanese short form were comparable with means
      for the 3 subtests for the older group and 2 subtests for the younger group. With
      the exception of the Auditory Digit Sequence, results suggested that both the
      Japanese short form and the initial Swanson Cognitive Processing Test measured
      comparably the working memory in the two samples of children.

PMID- 17037448
TI  - Turnover intentions of the faculty at a teaching-focused university.
AB  - Research on turnover in academia suggests faculty primarily resign to obtain
      higher salaries and for personal reasons; however, the samples of most such
      studies have been from research institutions. Correlates were examined for
      turnover intentions among 190 faculty members at a university that emphasized
      teaching. Although current turnover intention was low, seven measures of
      satisfaction explained 31.5% of the variability in turnover intent, and
      satisfaction with pay, work itself, and teaching/service load together explained
      26% of the variance. Findings support the hypothesis that salary is an important
      element in explaining turnover consideration at teaching institutions. Although
      satisfaction with collegial relations was related significantly to turnover
      intent, it was not as important as some of the other characteristics.

PMID- 17037449
TI  - A simplified version of the SYMLOG Trait Rating Form.
AB  - This paper describes a brief measure of Bales's three SYMLOG dimensions. A sample
      of 204 undergraduates with a mean age of 24.7 yr., 72.4% of whom were women,
      completed the usual version of the SYMLOG Trait Rating Form. This could also be
      scored as if it were a simplified version, omitting some items. The Simplified
      Measure of the SYMLOG Trait Rating Form correlated fairly highly with the full
      form--with r between .87 and .89 for the corresponding versions of all three
      scale dimension scores--making it a suitable substitute for research or
      illustrative purposes on occasions when respondents' time is of the essence.

PMID- 17037450
TI  - Effects of audience awareness on procedural text writing.
AB  - Effects of audience awareness were examined. Some participants acted as writers
      and the others acted as readers. Writers wrote a text describing a geometrical
      figure. Readers read the text and tried to draw the figure according to the
      description. In Exp. 1, audience awareness was manipulated among undergraduate
      students, 11 men and 34 women. Writers in the high audience-awareness condition
      spent more time planning and writing texts than writers in the low audience
      awareness condition. Texts in the high audience-awareness condition consisted of
      more letters and sentences with descriptions elaborating the texts. In Exp. 2,
      prototype texts were constructed based on the results of Exp. 1. Undergraduate
      students, 11 men and 47 women, who read the prototype text in the high audience
      awareness condition could draw the figure more accurately. In Exp. 3, effects of
      feedback from readers were examined. Ninth-grade students, 22 boys and 34 girls,
      participated as writers and 7th-grade students, 22 boys and 34 girls,
      participated as readers. Merely being told to attend to an audience did not
      improve the quality of texts written by 9th-grade students. However, feedback
      from the readers who were 7th-grade students was effective. Writers could revise
      the texts appropriately according to feedback and improve the quality of texts.
      In addition, the experience of revising the text according to feedback
      transferred to later writing. Educational implications of the results are
      discussed.

PMID- 17037451
TI  - Reliability and validity of the Parenting Scale of Inconsistency.
AB  - The purposes of the present study were to develop a Parenting Scale of
      Inconsistency and to evaluate its initial reliability and validity. The 12 items
      assess the inconsistency among parents' moods, behaviors, and attitudes toward
      children. In the primary study, 517 participants completed three measures: the
      new Parenting Scale of Inconsistency, the Parental Bonding Instrument, and the
      Depression Scale of the General Health Questionnaire. The Parenting Scale of
      Inconsistency had good test-retest reliability of .85 and internal consistency of
      .88 (Cronbach coefficient alpha). Construct validity was good as Inconsistency
      scores were significantly correlated with the Care and Overprotection scores of
      the Parental Bonding Instrument and with the Depression scores. Moreover,
      Inconsistency scores' relation with a dimension of parenting style distinct from
      Care and Overprotection suggested that the Parenting Scale of Inconsistency had
      factorial validity. This scale seems a potential measure for examining the
      relationships between inconsistent parenting and the mental health of children.

PMID- 17037452
TI  - A coding scheme for the evaluation of the relationship in music therapy sessions.
AB  - This study presents a coding system for observation and monitoring of changes in
      the interactive behaviour between patient and therapist during music therapy
      sessions. The coding scheme was developed from a psychodynamic framework and
      mainly consists of four behavioural classes: Verbal Communication, Nonverbal
      Communication, Countenance, and Sonorous Musical Communication. The 15 minutes in
      the middle of each videotape concerning the first active music therapy session-
      based on the sonorous musical improvisation--were coded. Subjects were children
      (4 boys; 3 girls) ages 3 to 10 years (M age = 6.3), diagnosed with Pervasive
      Developmental Disorder, and seven therapists. The method for data collection was
      continuous recording, applied through The Observer Video-Pro 5.0. For the
      reliability indexes there was a substantial agreement between assessments by
      video raters.

PMID- 17037453
TI  - The plural self and a Taoist orientation in two cultures.
AB  - A positive association between having a Taoist orientation to life and unity in
      the subjective perception of the self was found in samples of both American (n =
      99) and Turkish (n = 100) respondents.

PMID- 17037454
TI  - Anxiety and depression in Greek nursing and medical personnel.
AB  - The relatively low number of nurses compared to physicians in Greece and the few
      available studies on the psychological problems of the health professionals led
      to comparison of anxiety and depression for 76 Greek nursing personnel (20 men, M
      age: 32.8 yr., SD: 3.8 yr., and 56 women, M age: 36.6 yr., SD: 7.7 yr.) and 66
      doctors (35 men, M age: 35.9 yr., SD: 8.9 yr. and 31 women, M age: 32.7 yr., SD:
      8.1 yr.) using validated translations of the Spielberger State-Trait Anxiety
      Inventory and the Beck Depression Inventory. Male nurses had the lowest scores on
      trait anxiety, while female doctors had the highest scores, followed by female
      nurses. Depression scores were not different between doctors and nurses,
      regardless of sex. Age and depression scores were positively correlated (Spearman
      rho = .31) only for the female nurses. The findings suggest that interventions
      for diagnosis and stress management in the health-care workplace should be
      equally targeted for nursing and medical personnel.

PMID- 17037455
TI  - Association of maternal smoking during pregnancy and infant neurobehavioral
      status.
AB  - The association of maternal smoking during pregnancy with neurobehavioral status
      was examined in 344 Japanese infants. Based on a questionnaire, their mothers
      were classified into three groups, Nonsmokers, Exsmokers, and Smokers. The
      Neonatal Behavioral Assessment Scale was administered three days after birth.
      Among the three groups, on the seven clusters and their 28 behavioral subscales
      there were no significant differences. The infants of Smokers had lower scores
      than those of Exsmokers and Nonsmokers on two behavioral items, general tone and
      peak of excitement. General tone remained significant after adjustment for
      covariates.

PMID- 17037456
TI  - College students' perceived risk and anxiety after reading airplane crash news.
AB  - 328 college students in midwest and west coast regions read one of five news
      stories (four airplane crash and one irrelevant) or none. They estimated the
      likelihood of their victimization in an airplane crash and indicated the maximum
      amount of time that they would be willing to spend driving in lieu of flying.
      Analysis showed those who read one of the airplane crash stories reported higher
      perceived risk of victimization than did those who read the irrelevant story or
      none. Reading airplane crash news was not related to the number of hours reported
      for driving instead of flying.

PMID- 17037457
TI  - Time perspective as a potential tool for psychotherapeutic intervention.
AB  - This pilot study shows (1) similarities among adults in the patterns of
      organization of the past, present, and future based upon individual imagery and
      spatial representation of their personal perspective of their lives and (2) a
      relationship between perceived health and future-orientation, i.e., how far into
      their future a person imagines self still to be alive. The data support the
      concept of a personal spatial representation of past, present, and future (a
      timeline) and sets the foundation for the development of psychological
      interventions based on this representation for 50 participants (23 men and 27
      women). When asked to visualize their personal timelines, subjects indicated a
      general pattern of their future spatially located to the right and in front of
      themselves; their past was generally located to the left or behind. The distance
      into the future seen by participants initially (M +/- SE) were 8 +/- 2.3 yr., 16
      +/- 2.8 yr., and 27 +/- 5.5 yr. for the self-reported health status of "poor",
      "good", and "excellent", respectively (p < .05). Research must firmly establish
      general patterns of spatial representations of time (timeliness) across cultures,
      age, race, and beliefs, and explore implications for treatment.

PMID- 17037458
TI  - A validity generalization procedure to test relations between intrinsic and
      extrinsic motivation and influence tactics.
AB  - The relations of intrinsic and extrinsic motivation with use of consultative,
      legitimating, and pressure influence tactics were examined using validity
      generalization procedures. 5 to 7 field studies with cumulative samples exceeding
      800 were used to test each relationship. Significance was found for relation
      between agents' intrinsic motivation and their use of consultative influence
      tactics and agents' extrinsic motivation and their use of legitimating influence
      tactics.

PMID- 17037459
TI  - Concordance of self-reported abstinence and measurement of expired air carbon
      monoxide in a self-help smoking cessation treatment.
AB  - Some self-help programmes for smoking cessation obtain abstinence data entirely
      from participants' self-reports. This may lead to overestimation of efficacy. In
      the present study, the relationship between self-reported abstinence and expired
      air carbon monoxide was evaluated at the 12-mo. follow-up in 200 smokers who had
      participated in a self-help programme for smoking cessation conducted by mail.
      Analysis indicated a close relationship between carbon monoxide levels and self
      reports of smoking status; concordance was about 90%. Studies of the efficacy of
      self-help programmes for smoking cessation should include some sort of objective
      verification of self-reported abstinence.

PMID- 17037460
TI  - Ultimate, provisional, and personal meaning of life: differences and common
      ground.
AB  - Building on Viktor Frankl's clinical approach of Logotherapy and the works of
      subsequent theoreticians, three types of meaning of life were theoretically
      derived and empirically investigated, Ultimate, Provisional, and Personal
      meaning. These types were characterized, first, by the amount of agreement of
      subjects, second, by sources of Life Meaning, which were assessed by content
      analyses, third, by correlations, and fourth by prediction with ratings of
      important life concepts from the domains of Well-being, Religiosity, and
      Prosocial Behavior. 192 German adults, 45 men and 147 women, whose M age was 31.6
      yr. (SD = 11.9), participated. Analysis indicated different sources for the
      Ultimate meaning compared with the other meaning types, which seem to display
      more similarities with each other. Other important life concepts, such as Belief,
      Harmony, Happiness, and Human Goodness were related to the investigated types of
      meaning of life. Some implications for clinical applications, research
      perspectives, and Positive Psychology are discussed.

PMID- 17037461
TI  - Further examination of measurement properties of Spanish version of the Sexual
      Desire Inventory with undergraduates and adolescent students.
AB  - The factor structure and construct validity of a Spanish version of Spector,
      Carey, and Steinberg's Sexual Desire Inventory was examined with structural
      equation modelling and a nonclinical sample (N = 608). Confirmatory factor
      analysis indicated that Dyadic and Solitary sexual desire scales measured two
      factorially distinct constructs. Their internal consistency reliabilities were
      .87 and .88, respectively. Structural equation analysis indicated that both
      subscales are distinguishable from similarly conceptualized correlates of sexual
      desire: the Impersonal subscale of the Sex Fantasy Questionnaire and the
      Erotophilia measure of the Sexual Opinion Survey. However, the data raised some
      questions about an empirical distinction between dyadic sexual desire and
      intimate sexual fantasy.

PMID- 17037462
TI  - Teachers' conceptions of assessment: validation of an abridged version.
AB  - Psychometric characteristics of the abridged Teachers' Conceptions of Assessment
      III are reported. Data are from a study of 525 New Zealand primary school
      teachers and from a second study of 692 Queensland primary school teachers. The
      abridged version of 27 statements using a positively packed response scale had
      good fit characteristics for primary teachers in both New Zealand (chi(311)2 =
      841.02; RMSEA = .057; TLI = .87) and Queensland (chi(311)2 = 1492.61; RMSEA =
      .074; TLI = .80). While providing information of similar quality to that of the
      original the abridged version is more efficient than the full scale.

PMID- 17037463
TI  - Insomnia in relation to depression and somatic symptoms.
AB  - A sample of 358 Kuwaiti volunteer college students responded to the Insomnia
      Scale, the Somatic Symptoms Inventory, and the Center for Epidemiologic Studies
      Depression Scale. The only significant sex difference was in somatic symptoms on
      which women had a higher mean score than the men. Correlations between scores on
      the Insomnia Scale and both Depression scales were .51 and .54 and for Somatic
      Symptoms were .53 and .61 (p < .01) among men and women, respectively. The factor
      analysis of the intercorrelations yielded a highly loaded general factor for
      Psychological Disorder in both samples.

PMID- 17037465
TI  - Psychological support for junior high school students: sibling order and sex.
AB  - This study is a re-analysis of published data on psychological support for 609
      junior high school students (317 boys, 292 girls, mean age = 14.1, SD = 0.8)
      based on the self-report, Psychological Support Scale, to evaluate sibling order
      as eldest or youngest and sex. In an earlier study, the questionnaire had been
      modified to be applicable to junior high school students. The study re-examined
      the data by extracting samples for categories of eldest and youngest siblings,
      for re-analysis of self-reported psychological support by sibling order and sex.
      Eldest children reported receiving more psychological support from both mother
      and father than youngest. Also, eldest boys received significantly greater
      psychological support from both the parents than the youngest boys or girls.

PMID- 17037464
TI  - Prevalence of alcohol use by rural primary care outpatients in South Africa.
AB  - In a primary care outpatient sample of 600 rural South Africans 37.4% of men and
      10.7% of women were identified as hazardous drinkers, and 9.2% of men and 0.3% of
      women met criteria for probable alcohol dependence or harmful drinking as defined
      by AUDIT. Logistic multiple regression identified men and being single, divorced,
      or widowed as predictors for hazardous and harmful drinking.

PMID- 17037466
TI  - Association of race and color with mean IQ across nations.
AB  - This study investigated the correlation of both race and skin color in the
      distribution of mean IQ for 129 countries with primarily indigenous populations.
      Skin color correlated most highly with mean IQ across the Caucasoid countries (r
      = -.86), somewhat less across the Mongoloid countries (r = -.66), and
      nonsignificantly across the Negroid countries (r = .06). When the Negroid and
      Caucasoid countries were combined, both race and skin color yielded high
      correlations with IQ (r = .87, -.95, respectively). When the Negroid and
      Mongoloid countries were combined, both race and skin color yielded high
      correlations with IQ (r = .91, -.91, respectively). When Caucasoid and Mongoloid
      countries were combined, skin color yielded a high correlation, but race did not
      correlate significantly with IQ. The greater importance of Negroid race was
      regarded as congruent with the 1998 generalization of Jensen that the genetic
      distance between Mongoloids and Caucasoid is less than the genetic distance of
      these two groups from Negroid.

PMID- 17037467
TI  - Autobiographical memories of televised sporting events watched in different
      social settings.
AB  - The present study asked 157 men and 154 women to recall their memories of viewing
      both enjoyed and nonenjoyed televised sporting events from the past year in each
      of four social circumstances: with friends, with family, with spouse,
      boyfriend/girlfriend or significant other, and by oneself. For memories of all
      eight events, participants were asked (1) the number and sex of coviewers, (2)
      concurrent behaviors and cognitions engaged in while viewing, (3) uses and
      gratifications sought for enjoyed events, and (4) failed uses and gratifications
      for nonenjoyed events. Two analyses of variance, one full multiple regression,
      and one step-wise regression were conducted. Analyses indicated that social
      circumstance of viewing and sex of participant were associated with uses and
      gratifications for enjoyed events, failed uses and gratifications for nonenjoyed
      events, and concurrent behaviors and cognitions engaged in during the viewing.
      Results are discussed in light of the uses and gratifications paradigm and Wenner
      and Gantz's 1998 five fanship dimensions. An extension of this model to
      nonenjoyed sporting events is proposed.

PMID- 17037468
TI  - On structure of trauma-related stress reactions among people with diabetes
      mellitus.
AB  - The factorial structure of trauma-related stress reactions was explored using the
      Purdue Posttraumatic Stress Disorder revised scale, in a sample of 106 adults
      with insulin-dependent diabetes mellitus. An exploratory factor analysis yielded
      2 factors, (a) arousal and passive cognitive-affective avoidance reactions and
      (b) re-experiencing and active avoidance reactions. The 2-factor structure,
      however, may also be reflective of the scale format which limits its
      interpretative power.

PMID- 17037469
TI  - Processes of inference, schizotypal thinking, and obsessive-compulsive behaviour
      in a normal sample.
AB  - Previous research has shown inferential confusion as measured by the Inferential
      Confusion Questionnaire to be related to obsessive-compulsive symptoms. A total
      of 108 participants (41 men and 66 women) from a normal population in The
      Netherlands (M age = 46 yr., SD = 15.5) completed a package of questionnaires
      measuring inferential confusion, schizotypal symptoms, and obsessive-compulsive
      behaviour. As expected, scores for both inferential confusion and schizotypal
      symptoms were significantly related to those for obsessive-compulsive behaviour.
      In addition, analysis showed that inferential confusion and schizotypal symptoms
      shared common variance, but both predicted an independent portion of the variance
      in obsessive-compulsive behaviour while controlling for neuroticism. The present
      results call for further inquiry into the role of inferential confusion and
      schizotypal thinking in obsessive-compulsive behaviour.

PMID- 17037470
TI  - Re-analysis of correlations among four impulsivity scales.
AB  - Impulsivity plays a key role in normal and pathological behavior. Although there
      is some consensus about its conceptualization, there have been many attempts to
      build a multidimensional tool due to the lack of agreement in how to measure it.
      A recent study claimed support for a three-dimensional structure of impulsivity,
      however with weak empirical support. By re-analysing those data, a four-factor
      structure was found to describe the correlation matrix much better. The debate
      remains open and further research is needed to clarify the factor structure. The
      desirability of constructing new measures, perhaps analogously to the Wechsler
      Intelligence Scale, is emphasized.

PMID- 17037471
TI  - Correlates of mood changes in obese women initiating a moderate exercise and
      nutrition information program.
AB  - This 20-wk. study assessed relationships of mean difference scores on measures of
      self-efficacy and self-concept with scores for overall mood in 44 obese women who
      initiated a moderate exercise and nutrition information program. Simultaneous
      entry of changes in Physical Self-concept, Exercise Self-efficacy, and Body Areas
      Satisfaction scale scores into a multiple regression equation explained a
      significant 38% of the variance in changes in Total Mood Disturbance (R2 = .38,
      F3,40 = 8.09, p < .001).

PMID- 17037472
TI  - Correlates of low frustration tolerance in young adolescents.
AB  - 148 young adolescents who reported low frustration tolerance also reported more
      trait anger, state anger, and hostility.

PMID- 17037473
TI  - Exact and resampling probability values for measures associated with ordered r by
      c contingency tables.
AB  - Permutation procedures to compute exact and resampling probability values
      associated with measures of association for ordered r x c contingency tables are
      described. Comparisons with asymptotic probability values demonstrated that exact
      and resampling permutation procedures were preferred for sparse contingency
      tables.

PMID- 17037474
TI  - Factor structure of the Dysfunctional Attitude Scale (Form A) and the Automatic
      Thoughts Questionnaire: an exploratory study.
AB  - The factor structure of the Norwegian version of the Dysfunctional Attitude Scale
      and the Automatic Thoughts Questionnaire was investigated with a sample of 344
      male military recruits. Principal factor analyses with promax rotation indicated
      four factors for the former, labeled Performance Evaluation, Need for Approval,
      Autonomous Attitude, and Perfectionism which accounted for 15.5%, 3.6%, 2.6%, and
      2.5% of the total variance, respectively. Two factors comprised the latter.
      Factor 1 was labeled Negative Self-concept and Personal Maladjustment and
      accounted for 40% of the total variance, and Factor 2 was labeled Desire for
      Change and Negative Expectations and accounted for 6.3% of the total variance.
      The findings may be useful in identifying the specific dysfunctional beliefs and
      negative automatic thoughts exhibited by military recruits. Such information can
      also contribute to the development of more effective treatment interventions.

PMID- 17037475
TI  - Parental death and absence in children presenting for mental health care.
AB  - Of 61 youth (M age 11.2 yr.) seeking mental health care, almost 60% had
      experienced parental death or absence. 13 (21.3%) had experienced the death of a
      parent during the preceding 3 years.

PMID- 17037476
TI  - A measure of effect size for r x c contingency tables.
AB  - Goodman and Kruskal's tau measure of categorical association is advanced as a
      replacement for conventional measures of effect size for r x c contingency
      tables. Goodman and Kruskal's tau is an asymmetric measure of categorical
      association which is based entirely on the observed data and possesses a clear
      interpretation in terms of proportional reduction in error. Comparisons with
      conventional measures of effect size based on chi-squared such as Pearson's phi2,
      Tschuprow's T2, and Cramer's V2 demonstrate the advantages of employing tau as a
      measure of effect size.

PMID- 17037477
TI  - Anxiety and depression in cataract surgery: a pilot study in the elderly.
AB  - To assess anxiety induced by a planned cataract surgery and to evaluate the
      correlations of rated anxiety and depression with optical acuity pre- and post
      operatively, 278 patients ages 65 years or older were tested. Patients were
      divided into two groups: first-eye and second-eye cataract surgery. Anxiety and
      depression were evaluated using the Hamilton's Rating Scales for Anxiety and
      Depression, respectively. Pre-operatively, first-eye patients showed
      significantly higher anxiety than second-eye patients (F1,251 = 75.39, p < .001).
      First-eye patients rated peak anxiety on the day of the surgery, while patients
      scheduled for second-eye cataract surgery presented no fluctuations in rated
      anxiety (F1,251 = 49.60, p < .001). There was no correlation of preoperative
      anxiety or depression with the outcome of surgery (F(1,251)s = .83 and .58,
      respectively, p > .05). Postoperatively, anxiety and depression in patients
      without any improvement in their vision were rated significantly higher than in
      those presenting improved visual acuity after surgery (F1,251 = 566.17 and
      300.25, respectively, p < .001).

PMID- 17037478
TI  - Attitude toward Christianity and paranormal belief among 13- to 16-yr.-old
      students.
AB  - A small but statistically significant positive correlation (r = .17) was found in
      a sample of 279 13- to 16-yr.-old students in Wales between scores on the Francis
      Scale of Attitude toward Christianity and on a new Index of Paranormal Belief.
      These data suggest that there is little common variance between attitude toward
      Christianity and belief in the paranormal.

PMID- 17037479
TI  - Factor analysis to examine psychometric properties of family functioning
      measures.
AB  - To assess the relationship of family functioning to problem behaviors and alcohol
      and drug use among youth, researchers must test the effects of interventions
      using suitably constructed and psychometrically sound scales. This study
      evaluated whether originally calculated coefficients alpha underestimate the
      reliability of the family functioning measures given. Through exploratory factor
      analysis, estimates of alternative internal consistency reliability which might
      improve the estimate of reliability were examined. Responses of 755 adults from
      Strengthening Multi-ethnic Families and Communities were analyzed. Coefficients
      alpha for two scales were modest (alpha = .68 and alpha = .75), and factor
      analysis indicated that the scales were multidimensional. After exploratory
      factor analysis, the reassessment of reliability based on the extracted factors
      indicated an overall increase in the coefficients alpha.

PMID- 17037480
TI  - Cultural differences and economic development of 31 countries.
AB  - To update and extend the empirical research of Hofstede, the influence of culture
      on 31 nations' economic development was examined and support for modernization
      theory provided. Per capita gross domestic product, literacy rates, the negative
      of the population growth rate, and life expectancy development data were
      collected from 31 countries. The pattern of correlations among measures provided
      partial support for Hofstede's 1980 findings.

PMID- 17037481
TI  - Personality traits and university program.
AB  - Participants were 147 undergraduates majoring in programs classified as more
      professional (education, n = 28; business, n = 33) or less professional (natural
      sciences, n = 36; social science, n = 50) and more people-oriented (education,
      social sciences) or less people-oriented (business, natural sciences). They
      completed self-report tests for 13 personality constructs (five from Goldberg's
      version of the Five Factor Model, three from Eysenck and Eysenck's theory, and
      five others). Students in less professional disciplines scored higher on openness
      to experience (intellect/imagination) than those in more professional
      disciplines. Students in more people-oriented disciplines scored higher on
      empathy than those in less people-oriented disciplines. Women scored higher than
      men on conscientiousness, industriousness, and empathy, but lower than men on
      independence. Critical comments are offered and suggestions for research are
      made.

PMID- 17037482
TI  - Personality and attitude toward Christianity among churchgoers: a replication.
AB  - A sample of 158 churchgoers attending eight Anglican churches in the United
      Kingdom completed the abbreviated Revised Eysenck Personality Questionnaire
      together with the Francis Scale of Attitude toward Christianity to replicate a
      1996 study by Carter, Kay, and Francis. Data confirm that scores on Attitude
      toward Christianity were significantly negatively related to Psychoticism, but to
      neither Extraversion nor Neuroticism scores.

PMID- 17037483
TI  - Acculturation and suicide attitudes: a study of perceptions about suicide among a
      sample of Ghanaian immigrants in the United States.
AB  - To investigate whether a relationship exists between acculturation and attitudes
      about suicide, 81 Ghanaian immigrants living in the U.S. who responded to a mail
      inquiry were selected to participate in the current study. This particular
      immigrant sample was chosen because although they represent a rapidly growing
      group in the U.S., they have been rarely studied. Respondents consisted of 42
      women and 36 men (3 did not identify their sex), with a mean age of 29.5 yr. (SD
      = 10.6). Participants completed measures of acculturation and attitudes about
      suicide. Results indicated significant correlations between length of residency
      in the United States and negative suicide attitudes, and also between
      psychological acculturation and negative suicide attitudes. No significant
      relationship was found between behavioral acculturation and suicide attitudes.
      Furthermore, length of residency was a stronger predictor of suicide attitudes
      than other subjective measures of acculturation. Implications and suggestions for
      further research are discussed.

PMID- 17037484
TI  - Absolutism in diaries of suicides.
AB  - Two diaries, one from a completed suicide and one from an attempted suicide, were
      examined for the use of three words indicating absolutist thinking (perfect,
      always, and never). The diary of the attempted suicide had a significantly higher
      frequency use of "never" (2.75 per 1,000 words versus 1.73) but not the other
      words.

PMID- 17037485
TI  - "Self-execution" and state execution.
AB  - In the United States from 1977 to 1999, the suicide rate of death row inmates was
      not associated with their probability of execution (r = -.25).

PMID- 17037486
TI  - The metaphysical nuances of hylomorphism.

PMID- 17037487
TI  - A critique of oocyte-assisted reprogramming.

PMID- 17037488
TI  - Bibliography of secondary sources on the history of dermatology II. Obituaries
      and biographies in English supplemented through 2005 [corrected].

PMID- 17037489
TI  - Chimeras: from poetry to science.

PMID- 17037490
TI  - An overview of chimeras and hybrids.

PMID- 17037491
TI  - The strange case of the humanzee patent quest.

PMID- 17037492
TI  - How to navigate boundaries: a reply to The American Journal of Bioethics.

PMID- 17037493
TI  - Considering chimeras: the confluence of genetic engineering and ethics.

PMID- 17037494
TI  - Human brain cells in animal brains: philosophical and moral considerations.

PMID- 17037495
TI  - Is it ethical to generate human-animal chimeras?

PMID- 17037496
TI  - Catholic teaching on the human embryo as an object of research.

PMID- 17037497
TI  - The coronavirus replicase: insights into a sophisticated enzyme machinery.

PMID- 17037498
TI  - Biochemical aspects of coronavirus replication.

PMID- 17037499
TI  - A previously unrecognized UNR stem-loop structure in the coronavirus 5'
      untranslated region plays a functional role in replication.

PMID- 17037500
TI  - Regulation of coronavirus transcription: viral and cellular proteins interacting
      with transcription-regulating sequences.

PMID- 17037501
TI  - Deubiquitinating activity of the SARS-CoV papain-like protease.

PMID- 17037502
TI  - Nucleocapsid protein expression facilitates coronavirus replication.

PMID- 17037503
TI  - Non structural proteins 8 and 9 of human coronavirus 229E.

PMID- 17037504
TI  - Effects of mutagenesis of murine hepatitis virus nsp1 and nsp14 on replication in
      culture.
AB  - For nsp1, the fact that the carboxy-terminal but not the amino-terminal half of
      the protein can be deleted suggests that there may be specific and distinct
      domains within the protein or that the entire protein is dispensable but that the
      RNA encoding the amino-terminal half of nsp1 cannot be deleted. The
      identification of specific required residues support the conclusion that it is
      the portion of the protein that is required for replication. The results of
      mutagenesis of the nsp14 coding region and flanking cleavage sites also provided
      important new insights into this protein and its requirements. Our previous study
      raised the question as to the essential nature of nsp14 in replication. The
      results of this study show that putative active site residues cannot be
      substituted without loss of replication in culture. Interestingly, mutagenesis of
      Tyr414 showed that while this residue can tolerate a number of substitutions, it
      was intolerant of Lysine or deletion. The results suggest that nsp14 is required
      for replication. However, whatever functions nsp14 serves appear to be retained
      by noncleaved or partially processed nsp14, since abolition of either the amino
      terminal or carboxy-terminal cleavage site allowed recovery of viable virus.

PMID- 17037505
TI  - Mutational analysis of MHV-A59 replicase protein-nsp10.

PMID- 17037506
TI  - The nsp2 proteins of mouse hepatitis virus and SARS coronavirus are dispensable
      for viral replication.
AB  - The results presented here demonstrate that the MHV and SARS-CoV nsp2 proteins
      are not required for the production of infectious virus, for polyprotein
      expression or processing, or for viral replication complex formation in cell
      culture. The nsp2 protein domain resides in a region of the coronavirus replicase
      that is relatively nonconserved across coronaviruses. In fact, the size and amino
      acid sequence variability of nsp2 across the different coronaviruses has led some
      investigators to speculate that the nsp2 protein, along with the nsp1 and nsp3
      proteins, may play host- and/or cell-specific roles in the virus life cycle.
      While this may be the case, it should be noted that nsp2, in some form, exists in
      all coronaviruses studied to date and likely plays a pivotal role in the viral
      life cycle. A previous study from our laboratory identified a coronavirus
      replicase protein that plays an important role in viral pathogenesis. Such may
      prove to be the case for nsp2, as well. Alternatively, beacuse nsp2 exists as a
      detectable precursor protein nsp2-3 prior to processing of nsp2 and nsp3 into
      mature proteins, nsp2 may play a critical adaptor/regulatory role for nsp3
      function. Importantly, the viruses produced in this study provide a system by
      which the role of the nsp2 protein in viral infection can be characterized.

PMID- 17037507
TI  - Molecular dissection of porcine reproductive and respiratory virus putative
      nonstructural protein 2.

PMID- 17037508
TI  - Differential role of N-terminal polyprotein processing in coronavirus genome
      replication and minigenome amplification.

PMID- 17037509
TI  - Identification and characterization of severe acute respiratory syndrome
      coronavirus subgenomic RNAs.

PMID- 17037510
TI  - Identification and characterization of a unique ribosomal frameshifting signal in
      SARS-CoV ORF3a.

PMID- 17037511
TI  - ADP-ribose-1"-phosphatase activities of the human coronavirus 229E and SARS
      coronavirus X domains.

PMID- 17037512
TI  - Nonstructural proteins of human coronavirus NL63.

PMID- 17037513
TI  - MHV-A59 ORF1a replicase protein nsp7-nsp10 processing in replication.

PMID- 17037514
TI  - Stem-loop 1 in the 5' UTR of the SARS coronavirus can substitute for its
      counterpart in mouse hepatitis virus.

PMID- 17037515
TI  - Transcriptional regulation of RNA3 of infectious bronchitis virus.

PMID- 17037516
TI  - Structure, expression, and intracellular localization of the SARS-CoV accessory
      proteins 7a and 7b.

PMID- 17037517
TI  - Sumoylation of the nucleocapsid protein of severe acute respiratory syndrome
      coronavirus by interaction with Ubc9.

PMID- 17037518
TI  - Importance of MHV-CoV A59 nucleocapsid protein COOH-terminal negative charges.

PMID- 17037519
TI  - Expression and structural analysis of infectious bronchitis virus nucleoprotein.

PMID- 17037520
TI  - Mouse hepatitis virus infection activates the Ire1/XBP1 pathway of the unfolded
      protein response.

PMID- 17037521
TI  - The nuclear localization signal of the PRRS virus nucleocapsid protein viral
      replication in vitro and antibody response in vivo.

PMID- 17037522
TI  - SARS coronavirus accessory ORFs encode luxury functions.

PMID- 17037523
TI  - Production and characterization of monoclonal antibodies against the nucleocapsid
      protein of SARS-CoV.

PMID- 17037524
TI  - Mouse hepatitis coronavirus nucleocapsid phosphorylation.

PMID- 17037525
TI  - Genetic and molecular biological analysis of protein-protein interactions in
      coronavirus assembly.

PMID- 17037526
TI  - New insights on the structure and morphogenesis of Berne virus.

PMID- 17037527
TI  - Ultrastructure of SARS-CoV, FIPV, and MHV revealed by electron cryomicroscopy.

PMID- 17037529
TI  - The transmembrane domain of the infectious bronchitis virus E protein is required
      for efficient virus release.

PMID- 17037528
TI  - Role of mouse hepatitis coronavirus envelope protein transmembrane domain.

PMID- 17037530
TI  - Viroporin activity of SARS-CoV E protein.

PMID- 17037531
TI  - Efficient transduction of dendritic cells using coronavirus-based vectors.

PMID- 17037532
TI  - Insights from the association of SARS-CoV S-protein with its receptor, ACE2.

PMID- 17037533
TI  - Attachment factor and receptor engagement of SARS coronavirus and human
      coronavirus NL63.

PMID- 17037534
TI  - Interactions between SARS coronavirus and its receptor.

PMID- 17037535
TI  - Proteolysis of SARS-associated coronavirus spike glycoprotein.

PMID- 17037536
TI  - Fluorescence dequenching assays of coronavirus fusion.

PMID- 17037537
TI  - Porcine arterivirus entry in macrophages: heparan sulfate-mediated attachment,
      sialoadhesin-mediated internalization, and a cell-specific factor mediating virus
      disassembly and genome release.

PMID- 17037538
TI  - Enhancement of SARS-CoV infection by proteases.

PMID- 17037539
TI  - Increased viral titers and subtle changes in plaque morphology upon passage of
      SARS-CoV in cells from different species.

PMID- 17037540
TI  - Human coronavirus 229E can use CD209L (L-SIGN) to enter cells.

PMID- 17037541
TI  - Intracellular transport of the S proteins of coronaviruses.

PMID- 17037542
TI  - Analysis of SARS-CoV receptor activity of ACE2 orthologs.

PMID- 17037543
TI  - Interaction between the spike protein of human coronavirus NL63 and its cellular
      receptor ACE2.

PMID- 17037544
TI  - Human angiotensin-converting enzyme 2 (ACE2) is a receptor for human respiratory
      coronavirus NL63.

PMID- 17037545
TI  - Molecular interactions of group 1 coronaviruses with feline APN.

PMID- 17037546
TI  - Pseudotyped vesicular stomatitis virus for functional analysis of SARS
      coronavirus spike protein.

PMID- 17037547
TI  - Subcellular localization of SARS-CoV structural proteins.

PMID- 17037548
TI  - Spike gene determinants of mouse hepatitis virus host range expansion.

PMID- 17037549
TI  - Virion-liposome interactions identify a cholesterol-independent coronavirus entry
      stage.

PMID- 17037551
TI  - Three-dimensional reconstruction of the nucleolus using meta-confocal microscopy
      in cells expressing the coronavirus nucleoprotein.

PMID- 17037550
TI  - Avian infectious bronchitis virus enters cells via the endocytic pathway.

PMID- 17037552
TI  - Dissection of the fusion machine of SARS-coronavirus.

PMID- 17037553
TI  - Characterization of persistent SARS-CoV infection in Vero E6 cells.

PMID- 17037554
TI  - Receptor-independent spread of a neurotropic murine coronavirus MHV-JHMV in mixed
      neural culture.

PMID- 17037555
TI  - Receptor-independent infection of mouse hepatitis virus: analysis by
      spinoculation.

PMID- 17037556
TI  - SARS-CoV, but not HCoV-NL63, utilizes cathepsins to infect cells: viral entry.

PMID- 17037557
TI  - Coronavirus immunity: from T cells to B cells.

PMID- 17037558
TI  - Rat coronavirus infection of primary rat alveolar epithelial cells.

PMID- 17037559
TI  - Infectious bronchitis coronavirus induces cell-cycle perturbations.

PMID- 17037560
TI  - Genes 3 and 5 of infectious bronchitis virus are accessory protein genes.

PMID- 17037561
TI  - NKG2D signaling and host defense after mouse hepatitis virus infection of the
      central nervous system.

PMID- 17037562
TI  - Murine hepatitis virus strain 1 as a model for severe acute respiratory distress
      syndrome (SARS).

PMID- 17037563
TI  - Persistent coronavirus infection of progenitor oligodendrocytes.

PMID- 17037564
TI  - CD8+ T-cell priming during a central nervous system infection with mouse
      hepatitis virus.

PMID- 17037565
TI  - Antibody-mediated virus clearance from neurons of rats infected with
      hemagglutinating encephalomyelitis virus.

PMID- 17037566
TI  - Developing bioinformatic resources for coronaviruses.

PMID- 17037567
TI  - Autoantibodies exacerbate the severity of MHV-induced encephalitis.

PMID- 17037568
TI  - Analysis of the N protein in feline coronavirus strains in Italy.

PMID- 17037569
TI  - Differential induction of proinflammatory cytokines in primary mouse astrocytes
      and microglia by coronavirus infection.

PMID- 17037570
TI  - Preferential infection of mature dendritic cells by the JHM strain of mouse
      hepatitis virus.

PMID- 17037571
TI  - Role of the replicase gene of murine coronavirus JHM strain in hepatitis.

PMID- 17037572
TI  - Identification of the receptor for FGL2 and implications for susceptibility to
      mouse hepatitis virus (MHV-3)-induced fulminant hepatitis.

PMID- 17037573
TI  - Equine viral arteritis.
AB  - EVA is an important if uncommon disease of horses. Potential economic losses
      attributable to EVA include direct losses from abortion, pneumonia in neonates,
      and febrile disease in performance horses. Indirect losses are those associated
      with national and international trade/animal movement regulations, particularly
      those pertaining to persistently infected carrier stallions and their semen.
      However, EAV infection and EVA are readily prevented through serological and
      virological screening of horses, coupled with sound management practices that
      include appropriate quarantine and strategic vaccination.

PMID- 17037574
TI  - Use of a PRRSV infectious clone to evaluate in vitro quasispecies evolution.

PMID- 17037575
TI  - Gamma-interferon involvement in the pathogenesis of lactate dehydrogenase
      elevating virus infection.

PMID- 17037576
TI  - Replication and expression analysis of PRRSV defective RNA.

PMID- 17037577
TI  - Efficacy of an inactivated PRRSV vaccine: induction of virus-neutralizing
      antibodies and partial virological protection upon challenge.

PMID- 17037578
TI  - SARS and other coronaviruses in humans and animals.

PMID- 17037579
TI  - Animal models for SARS.

PMID- 17037580
TI  - HCoV-OC43-induced apoptosis of murine neuronal cells.

PMID- 17037581
TI  - Infection of human airway epithelia by SARS coronavirus is associated with ACE2
      expression and localization.

PMID- 17037582
TI  - Human coronavirus NL63 infection is associated with croup.

PMID- 17037583
TI  - A SARS-CoV-specific protein enhances virulence of an attenuated strain of mouse
      hepatitis virus.

PMID- 17037584
TI  - Genetic evolution of human coronavirus OC43 in neural cell culture.

PMID- 17037585
TI  - Synergistic inhibition of SARS-coronavirus replication by type I and type II IFN.

PMID- 17037586
TI  - Mustela vison ACE2 functions as a receptor for SARS-coronavirus.

PMID- 17037587
TI  - HCoV-229E infects and activates monocytes.

PMID- 17037589
TI  - Identification of ferret ACE2 and its receptor function for SARS-coronavirus.

PMID- 17037588
TI  - Pathological and virological analyses of severe acute respiratory syndrome
      associated coronavirus infections in experimental animals.

PMID- 17037590
TI  - Human coronavirus-NL63 infection is not associated with acute Kawasaki disease.

PMID- 17037591
TI  - Toward the development of an infectious cDNA clone of a human enteric
      coronavirus.

PMID- 17037592
TI  - HCoV-OC43-induced encephalitis is in part immune-mediated.

PMID- 17037593
TI  - SARS CoV replication and pathogenesis in human airway epithelial cultures.

PMID- 17037594
TI  - Immunogenicity of SARS-CoV: the receptor-binding domain of S protein is a major
      target of neutralizing antibodies.

PMID- 17037595
TI  - Glia expression of MHC during CNS infection by neurotropic coronavirus.

PMID- 17037596
TI  - Resurrection of an "extinct" SARS-CoV isolate GD03 from late 2003.

PMID- 17037597
TI  - SARS coronavirus vaccine development.

PMID- 17037598
TI  - Development of vaccines and passive immunotherapy against SARS coronavirus using
      mouse and SCID-PBL/hu mouse models.
AB  - We have investigated novel vaccines strategies against severe acute respiratory
      syndrome (SARS) CoV infection using cDNA constructs encoding the structural
      antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein,
      derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to
      infect the alveolar epithelial cell of the lung,in the present study, a type II
      alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL
      against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M)
      DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL
      induction and proliferation) against type II alveolar epithelial cells (T7)
      transfected with SARS (N) or (M) DNA, respectively. To determine whether these
      DNA vaccines could induce T-cell immune responses in humans as well as in mice,
      SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human
      volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD
      SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to
      analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized
      with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The
      M DNA vaccine enhanced CTL activity and proliferation in the presence of M
      peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL
      activity (IFN-gamma production by recombinant N protein or N protein-pulsed
      autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice.
      These results, demonstrate that SARS M and N DNA vaccines induced human CTL and
      human T-cell proliferative responses. On the other hand, we have developed SARS
      DNA vaccines that induce human neutralizing antibodies and human monoclonal
      antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor
      (angiotensin converting enzyme 2) are also under development. These vaccines are
      expected to induce immune responses specific for SARS CoV in human and should
      provide useful tool for development of protective vaccines.

PMID- 17037599
TI  - Inhibition and escape of SARS-CoV treated with antisense morpholino oligomers.

PMID- 17037600
TI  - Validation of coronavirus E proteins ion channels as targets for antiviral drugs.

PMID- 17037601
TI  - Identification of essential genes as a strategy to select a SARS candidate
      vaccine using a SARS-CoV infectious cDNA.

PMID- 17037602
TI  - Structure and dynamics of SARS coronavirus main proteinase (Mpro).

PMID- 17037603
TI  - Highly attenuated vaccinia virus DIs as a potential SARS vaccine.

PMID- 17037604
TI  - Renilla luciferase as a reporter to assess SARS-CoV mRNA transcription regulation
      and efficacy of anti-SARS-CoV agents.

PMID- 17037605
TI  - Virucidal effect of a newly developed nickel alloy on mouse coronavirus.

PMID- 17037606
TI  - Construction of a full-length cDNA infectious clone of a European-like Type 1
      PRRSV isolated in the U.S.

PMID- 17037608
TI  - To an athlete, aching young.

PMID- 17037607
TI  - Identification and evaluation of coronavirus replicase inhibitors using a
      replicon cell line.

PMID- 17037609
TI  - Test strategies in bovine viral diarrhea virus control and eradication campaigns
      in Europe.
AB  - Several European countries have initiated national and regional control-and
      eradication campaigns for bovine viral diarrhea virus (BVDV). Most of these
      campaigns do not involve the use of vaccines; in Germany, vaccination is used
      only in states in which it is considered necessary because of high BVDV
      prevalence. In European countries without organized BVDV control programs,
      vaccination is commonly used to control BVDV. Diagnostic test strategies are
      fundamental to all control-and-eradication campaigns; therefore, the purpose of
      this review is to describe how the available diagnostic tests are combined into
      test strategies in the various phases of control-and-eradication campaigns in
      Europe. Laboratory techniques are available for BVDV diagnosis at the individual
      animal level and at the herd level. These are strategically used to achieve 3
      main objectives: 1) initial tests to classify herd status, 2) follow-up tests to
      identify individual BVDV-infected animals in infected herds, and 3) continued
      monitoring to confirm BVDV-free status. For each objective or phase, the validity
      of the diagnostic tests depends on the mode of BVDV introduction and duration of
      infection in test-positive herds, and on how long noninfected herds have been
      clear of BVDV. Therefore, the various herd-level diagnostic tools--such as
      antibody detection in bulk milk or in blood samples from young stock animals, or
      BVDV detection in bulk milk--need to be combined appropriately to obtain
      effective strategies at low cost. If the individual diagnostic tests are used
      with due consideration of the objectives of a specific phase of a BVDV control
      program, they are effective tools for controlling and eradicating BVDV in regions
      not using vaccination and where vaccination is a part of the control or
      eradication program.

PMID- 17037610
TI  - Detection of antibodies in serum and egg yolk following infection of chickens
      with an H6N2 avian influenza virus.
AB  - Active serologic surveillance programs to detect avian influenza viruses (AIVs)
      in table egg-laying chickens have been initiated by several states as a response
      to the economic threat posed by these viruses. Most outbreaks of avian influenza
      in domestic poultry are caused by mildly pathogenic AIVs. In the study reported
      here, infection by an H6N2 AIV was used as a model of mildly pathogenic AIV
      infections in egg-type chickens. The total number of eggs laid by 5 control hens
      was 619 or 0.904 eggs/day/hen, whereas the total number laid by 10 infected hens
      was 1,018 or 0.743 eggs/day/hen. The difference in egg production between the 2
      groups was not statistically significant (P = 0.38). Anti-influenza antibodies
      were monitored by use of an agar gel immunodiffusion test and an ELISA for a
      period of 20 weeks after inoculation. Antibodies in serum developed sooner,
      peaked at higher levels, and remained at higher levels than did antibodies found
      in egg yolk, as indicated by ELISA results. For infected chickens, the
      correlation between serum and egg yolk ratios was 0.66. Serum samples would
      appear to be preferable to egg yolk samples for surveillance programs intended to
      identify chicken flocks that may have been infected by an AIV weeks or months
      before samples are collected.

PMID- 17037611
TI  - Determination of sheep prion gene polymorphisms from paraffin-embedded tissue.
AB  - Amino acid polymorphisms of the prion protein (PrP) greatly influence the
      susceptibility of sheep to scrapie. Selective breeding to increase the prevalence
      of PrP gene alleles associated with scrapie resistance is a flock management
      practice that is important for scrapie control programs. Determination of sheep
      PrP alleles typically has required extraction of DNA from host tissues that are
      freshly derived or stored frozen. We describe application of a DNA extraction
      procedure for formalin-fixed, paraffin-embedded tissues (PET) for the purpose of
      PCR amplification and nucleotide sequencing of relevant codons (136-171) of the
      sheep PrP gene. Tissues derived from 96 sheep were studied. The DNA sequence
      identity was confirmed in 87 of 94 matched samples of PET and frozen tissue
      specimens. DNA from brainstem PET of 2 sheep, from which fresh tissue was not
      available, was amplified and sequenced after formalin fixation for 7-70 days.
      This method will allow retrospective analysis of PrP genetics of sheep subsequent
      to postmortem diagnosis of scrapie when nonfixed tissue is unavailable for DNA
      extraction; however, it is not recommended that submission of fixed tissue
      supplant collection of fresh tissues for the purpose of determining PrP gene
      polymorphisms.

PMID- 17037612
TI  - Comparison of milk and serum enzyme-linked immunosorbent assays for diagnosis of
      Mycobacterium avium subspecies paratuberculosis infection in dairy cattle.
AB  - Milk and serum samples from 35 dairy herds in 17 states were evaluated for cow-
      and herd-level Mycobacterium avium subspecies paratuberculosis (MAP) antibody
      test agreement. Evaluation of 6,349 samples suggested moderate agreement between
      milk and serum enzyme-linked immunosorbent assay (ELISA) results, with a kappa
      value of 0.50. Cow-level sensitivity (Se) for 18 dairy operations with 1,921
      animals was evaluated relative to fecal culture results. At the cow level, the
      milk ELISA relative Se was not significantly different from that of the serum
      ELISA (21.2 and 23.5%, respectively). Logistic regression models revealed a
      positive association between lactation number and milk ELISA status. Non-Holstein
      cows were more likely to test milk ELISA positive than Holstein cows. Cows in the
      first 2 weeks of lactation and after week 45 of lactation were more likely to
      test milk ELISA positive than cows between 3 and 12 weeks of lactation. Milk
      production > 80% of herd average was negatively associated with testing milk
      ELISA positive. Animals in the West and Midwest regions were less likely than
      animals in the Southeast region to test ELISA positive by either test. Estimates
      for herd-level sensitivity for the milk and serum ELISA, relative to fecal
      culture results, ranged from 56 to 83%. At the cow and herd levels, milk ELISA
      performed equivalent to serum ELISA using fecal culture as a reference for MAP
      infection and has the advantage of decreased labor costs on farms that use Dairy
      Herd Improvement Association testing.

PMID- 17037613
TI  - A new fluorogenic real-time RT-PCR assay for detection of lineage 1 and lineage 2
      West Nile viruses.
AB  - West Nile virus represents an emerging threat for animal and human health
      worldwide. This virus exhibits a marked genetic variation, with at least 2
      distinct evolutionary lineages. Lineage 1 has been recognized in Africa, Asia,
      Europe, Oceania, and more recently in the Americas, whereas lineage 2 is
      restricted to Africa. Perhaps for this reason, the available real-time RT-PCR
      methods for detecting West Nile virus genome have mainly focused on lineage 1.
      However, both viruses may potentially be spread beyond their endemic areas by
      migratory birds. This report describes a new real-time reverse transcription-PCR
      (RT-PCR) method based on a 5'-Taq nuclease-3' minor groove binder DNA probe
      (TaqMan MGB) that allows the detection of a wide range of West Nile virus
      isolates, including both lineages 1 and 2. This method was able to detect West
      Nile viruses from different origins (North and Central Africa, Middle East,
      Europe, and North America), whereas other flaviviruses (Usutu, Dengue, Yellow
      fever) analyzed in parallel remained negative. The sensitivity achieved by this
      assay was 10(-2)-10(-3) pfu/tube. This method, which can be performed in 96-well
      format, could be suitable for the large-scale surveillance of West Nile virus in
      areas where both lineages can potentially spread.

PMID- 17037614
TI  - Detection of hepatitis E virus shedding in feces of pigs at different stages of
      production using reverse transcription-polymerase chain reaction.
AB  - The aim of this study was to determine at which production stages hepatitis E
      virus (HEV) is shed by the highest number of pigs and to estimate the relative
      risk associated with each stage. For this purpose, 146 fecal samples of pigs from
      21 farms were studied. In addition, 1 sample from the manure ditch and another
      sample of drinking water, collected directly from the trough located in the pen,
      were taken from 16 farms. HEV RNA was detected in fecal samples from 34 pigs
      (23.29%). The production stages in which most pigs excreted HEV were weaners
      (41.7%) and pigs in the first month of feeding (60%). The results of the
      statistical analysis showed that the principal significant risk stage in HEV
      shedding was the first month of feeding (odds ratio [OR] 19.5, 95% CI 3.59
      106.07, P = 0.001) followed by the weaners stage (OR 9.3, 95% CI .78-48.42, P =
      0.008). In 8 out of 16 farms tested (50%) HEV RNA was detected in raw manure and
      in the water trough of only 1. Detection of HEV in manure ditches raises the
      concern of how to deal with manure of swine origin, because it is used as soil
      fertilizer.

PMID- 17037615
TI  - Effect of hemolysis on nonesterified fatty acid and beta-hydroxybutyrate
      concentrations in bovine blood.
AB  - Nonesterified fatty acid (NEFA) and beta-hydroxybutyrate (BHB) assays are used
      for evaluating dairy herds for negative energy balance and subclinical ketosis,
      respectively. Hemolysis is a common artifact in samples submitted to diagnostic
      laboratories. The effect of hemolysis on NEFA and BHB in bovine serum was
      determined. Hemolysis was introduced into 26 serum samples by adding serial
      dilutions of a red cell hemolysate, prepared by repeated freeze-thawing of EDTA
      anticoagulated bovine blood. NEFA, BHB, and degree of hemolysis (hemolytic index)
      were measured by an automated chemistry analyzer. Two endpoint assays that
      differed by inclusion of a sample blank were used for NEFA measurement. A kinetic
      enzymatic assay with 2 reagent sources was used for BHB measurement. The assessed
      methods yielded similar NEFA or BHB results in baseline, nonhemolyzed samples
      (median NEFA: 0.25 mEq/L, median BHB: 3 mg/dL, median hemolytic index: 8 units).
      NEFA results were adversely affected by hemolysis, with values increasing
      significantly with higher degrees of hemolysis. Median values increased above a
      critical medical decision limit (0.40 mEq/L) at a hemolytic index of 506 units
      (marked hemolysis). This increase was prevented by inclusion of a sample blank.
      Result interpretation was affected in individual animals when samples were
      moderately hemolyzed (median hemolytic index: 258 units). In contrast, BHB
      results were unaffected by hemolysis with either reagent source. Thus, assays for
      measuring NEFAs should include a sample blank and NEFA results should not be
      interpreted in moderately to markedly hemolyzed bovine samples, because result
      accuracy cannot be assured.

PMID- 17037616
TI  - Comparison of cytogenetics and polymerase chain reaction based detection of the
      amelogenin gene polymorphism for the diagnosis of freemartinism in cattle.
AB  - A polymerase chain reaction (PCR) assay which detects a sex-based polymorphism in
      the bovine amelogenin locus was modified and compared to conventional cytogenetic
      analysis for diagnosis of freemartinism (XX/XY chimerism) in cattle. The PCR
      assay is more sensitive than cytogenetic analysis for detection of XY cells, with
      the limit of detection of the assay falling between 0.2% and 1% XY cells. Seventy
      three heifer blood samples submitted for evaluation of freemartinism to the
      University of Minnesota Diagnostic Laboratory were tested using both cytogenetic
      and PCR techniques. Poor-quality samples precluded successful lymphocyte culture
      and recovery of mitotic nuclei for cytogenetic evaluation in 17 cases (23%). Two
      of these samples (2.7%) also failed to amplify with PCR. There was 100% agreement
      in the results from the 56 samples that were suitable for testing using both
      techniques. This PCR-based assay provides an alternative to the more laborious
      cytogenetic evaluation for diagnosis of freemartinism.

PMID- 17037617
TI  - Isolation of equine herpesvirus-5 from blood mononuclear cells of a gelding.
AB  - Horses are commonly infected by herpesviruses, but isolation of equine
      herpesvirus-5 (EHV-5) has only infrequently been reported. We describe the
      isolation and characterization of a strain of EHV-5 from the blood mononuclear
      cells of a healthy adult horse in California. The virus was initially identified
      by EHV-5 specific polymerase chain reaction (PCR), and it caused lytic infection
      of cultured rabbit kidney cells only after repeated serial passage. Virions with
      characteristic herpesvirus morphology were readily demonstrated in cell culture
      lysate by transmission electron microscopy. A portion of the glycoprotein B gene
      of this strain of EHV-5 had 99% identity to the published EHV-5 sequence, and it
      was clearly distinguishable from other EHV (1-4) by virus-specific PCR assays.
      Prevalence of EHV-5 infection in a group of young racehorses was estimated at 64%
      using the EHV-5 specific PCR on nasopharyngeal secretions.

PMID- 17037619
TI  - Distribution of equine infectious anemia in horses in the north of Minas Gerais
      State, Brazil.
AB  - The paper examines the prevalence of equine infectious anemia (EIA) in horse
      populations in the northern part (comprising 89 cities) of Minas Gerais State,
      Brazil, from January 2002 to December 2004. Data on 8,981 agar gel
      immunodiffusion test results from the region were used as input for a statistical
      and autoregressive analysis model to construct a city-level map of the
      distribution of EIA prevalence. The following EIA prevalence (P) levels were
      found: 49 cities with 0 < P < or = 0.5%, 26 with 0.5% < P < or = 1.5%, 10 with
      1.5% < P < or = 5%, and 4 with 5% < P < or = 25%.

PMID- 17037618
TI  - Goat paratuberculosis in Chile: first isolation and confirmation of Mycobacterium
      avium subspecies paratuberculosis infection in a dairy goat.
AB  - In October 2004, 41 goats > 2 years old from a Saanen dairy goat herd located in
      Purranque County, 10th Region, Chile, were sampled and tested for
      paratuberculosis. While collecting samples it was observed that several goats
      were thin and emaciated. One goat was sufficiently debilitated to warrant humane
      euthanasia. This animal was brought to the Veterinary School at the Universidad
      Austral de Chile for necropsy. The goat selected for necropsy was a 12-year-old
      doe. The animal showed classical clinical signs of caprine paratuberculosis:
      emaciation despite willingness to eat, dry and rough hair coat, and no evidence
      of diarrhea. Gross pathology and histopathology of the necropsied goat were
      consistent with paucibacillary paratuberculosis. Bacteriology, serology, and PCR
      confirmed the diagnosis. This is the first published report of goat
      paratuberculosis in Chile confirming a case of caprine paucibacillary
      paratuberculosis.

PMID- 17037620
TI  - Chlorophacinone exposure causing an epizootic of acute fatal hemorrhage in lambs.
AB  - This report describes an epizootic of chlorophacinone toxicosis in lambs with
      severe acute hemorrhages. Eleven lambs, approximately 1-2 months of age, suddenly
      developed epistaxis, respiratory distress, and facial and cervical swelling.
      Affected animals died within 1-2 hours from the onset of clinical signs. Two
      lambs were available for complete postmortem examination. Gross lesions included
      mucosal and organ pallor, icterus, melena, and lung edema, as well as thymic,
      cervical muscle, and intra-articular hemorrhage. Histologically hepatocellular
      centrolobular necrosis was observed. The anticoagulant chlorophacinone was
      detected in the livers at 0.58 ppm and 0.50 ppm (wet weight), respectively. The
      source of exposure to chlorophacinone was old bait material placed between the
      wall studs of the building housing the ewes and lambs. The lambs were able to
      reach the bait through a hole in the plywood interior wall of the building.

PMID- 17037621
TI  - Acute anhydrous ammonia intoxication in cattle.
AB  - Intoxication with anhydrous ammonia (AA) is a common occupation-related health
      problem affecting farmers and fertilizer applicators, however, very few
      descriptions of animal exposure to this toxicant exist. Thieves entered a feedlot
      and damaged a liquid AA storage tank, resulting in the accidental leakage of gas
      from a valve. Overnight, 12 cattle were found dead, with a total mortality of 64
      cattle out of 260 on the premises dying or euthanized in < 1 week. Signs of
      affected cattle included blindness, drooling, inappetence, respiratory distress,
      recumbency, and death. Two cattle were submitted live for diagnostic evaluation 3
      days after initial exposure. Gross lesions included corneal ulcers,
      fibrinonecrotizing rhinitis, hemorrhages within the nasal sinuses, and
      anterioventral bronchopneumonia. Microscopic lesions consisted predominantly of
      degeneration and necrosis of superficial epithelium lining nasal passages,
      trachea, and pulmonary airways. This case illustrates the acute AA effects on
      cattle, which is likely to be an increasingly encountered problem because of on
      farm storage of AA and its access by illicit drug manufacturers.

PMID- 17037622
TI  - Vitamin A deficiency in turkey poults.
AB  - Vitamin A deficiency was diagnosed in a commercial flock of 13,000 4-6-week-old
      turkey poults in the summer of 2004. The birds were initially submitted for
      examination because of a 3% increase in the reported daily mortality of the
      flock. Clinically, affected birds had stunted growth and ruffled feathers, showed
      signs of incoordination, and were depressed. At necropsy, pale white
      pseudomembranous to mucoid material was observed on the mucosal surface of the
      tongue, oral cavity, portions of the esophagus, and the crop of some birds.
      Histologically, there was squamous metaplasia of the mucosal epithelium of the
      oral mucosa, esophagus, sinuses, nasal glands, bronchi, proventriculus, and the
      bursa of Fabricius. Vitamin A was not detected in the feed sample at a detection
      limit of 0.5 mg/kg. Serum vitamin A concentrations in 7 birds were very low and
      ranged from 0.05 to 0.1 mg/L. Vitamin A concentrations in livers were extremely
      low (0.1 mg/kg wet weight, 1/7 poults) or undetectable (< 0.1 mg/kg wet weight,
      6/7 poults). A diagnosis of vitamin A deficiency was made based on gross and
      microscopic lesions and vitamin A concentrations in serum, liver, and feed. To
      the authors' knowledge, this is the first documented case of vitamin A deficiency
      in poults submitted from a commercial meat turkey producer comparatively
      depicting the gross and microscopic lesions with those found in other species of
      birds and mammals.

PMID- 17037623
TI  - Monensin toxicosis in water buffaloes (Bubalus bubalis).
AB  - The consumption of monensin-containing feed resulted in deaths of water buffaloes
      from a feedlot in which cattle and buffaloes were kept together. The monensin
      formulation was recommended only for use in cattle. Anorexia, muscular weakness,
      dyspnea, and recumbency were the major clinical findings. The most significant
      gross lesions were focal pale areas in semitendinosus and semimembranosus
      muscles, in which segmental necrosis of myofibers was seen microscopically. To
      compare susceptibilities of species to monensin, 3 bovine calves and 3 buffalo
      calves were orally dosed. At 5, 7.5, and 10 mg/kg of monensin, only the buffaloes
      became ill and died. Clinical signs initiated 18-20 h postdosing and were
      comparable to those from field cases. Gross changes consisted of ascites,
      hydrothorax, hydropericardium, hepatomegaly, and focal pale areas in the
      myocardium and to a lesser degree in semitendinosus and semimembranosus muscles.
      Histopathological changes also resembled those from the field cases, but were
      especially pronounced in the myocardial cells. The hypothesis that buffaloes
      could have a lower tolerance to monensin than cattle has been supported by
      experimental cases.

PMID- 17037624
TI  - Renal tubular necrosis and interstitial hemorrhage ("turkey-egg kidney") in a
      circovirus-infected Yorkshire cross pig.
AB  - A juvenile Yorkshire cross pig with rapidly progressive acute renal failure was
      submitted for necropsy. There was marked edema and disseminated petechiation of
      both kidneys, producing the "turkey-egg" appearance that is characteristic of
      exotic diseases such as African and classical swine fever. Microscopic findings
      included renal tubular epithelial necrosis with extensive interstitial edema and
      hemorrhage; lymphoplasmacytic, eosinophilic, and histiocytic tubulointerstitial
      nephritis; and numerous botryoid intracytoplasmic inclusions within the renal
      tubular epithelium and interstitial macrophages. Porcine circovirus 2 (PCV2) was
      readily identified within these lesions by both PCV2-specific
      immunohistochemistical staining and electron microscopy. Tests for African and
      classical swine fever viruses, as well as bacterial cultures, were negative. The
      striking renal lesions in this pig were attributed to PCV2 infection and are
      distinct from those that are typical of other PCV2-associated diseases.

PMID- 17037625
TI  - Malignant nonteratoid ocular medulloepithelioma in a llama (Llama glama).
AB  - A 6-year-old female llama presented with buphthalmos of its right eye owing to
      the presence of an intraocular mass. The affected globe was enucleated and
      submitted for microscopic examination. The intraocular mass was diagnosed as
      malignant medulloepithelioma. Within the following months, the llama developed
      soft tissue masses, which completely filled the right orbital cavity and expanded
      the cranial portion of the right mandibular bone, and enlarged mandibular lymph
      nodes. Euthanasia was elected 30 months after the initial diagnosis. The carcass
      was submitted for postmortem examination, which revealed the presence of
      medulloepithelioma metastases within the right orbit, mandible, mandibular lymph
      nodes, lungs, liver, and mesenteric and sublumbar lymph nodes. The primary
      intraocular tumor and its metastases were composed of neoplastic undifferentiated
      neuroepithelial cells, which formed tubules, Flexner-Wintersteiner and Homer
      Wright rosettes, and rare solid sheets. Electron microscopy showed that tumor
      cells were connected by desmosome-like junctions and contained rare
      intracytoplasmic basal bodies. Neoplastic cells were positive for vimentin,
      nestin, microtubule-associated protein 1B, S-100 protein, and glial fibrillary
      acidic protein (GFAP). To the best of the authors' knowledge, this is the first
      report of a malignant nonteratoid ocular medulloepithelioma with distant
      metastases in a llama and of the ultrastructural and extended immunohistochemical
      characterization of a nonteratoid medulloepithelioma in this species.

PMID- 17037626
TI  - Mixed thymoma in a cow.
AB  - A neoplastic mass measuring 25 x 8 x 3 cm was found in the mediastinum of a 10
      year-old Holstein cow. The neoplasm was encapsulated, multilobulated, and cystic.
      Several firm adhesions were present between the neoplasm and the right cranial
      lung lobe and the ipsilateral side of the pericardial sac. Under microscopic
      examination, the neoplasm was characterized by solid sheets of spindle epithelial
      cells (pancytokeratin and high molecular weight cytokeratin positive) subdivided
      by fibrous trabeculae. Numerous individualized or small aggregates of mature T
      cell (CD3 positive) lymphocytes were scattered throughout the neoplastic cell
      population. Based on the gross, histologic, and immunohistochemical findings, the
      neoplasm was diagnosed as a mixed thymoma.

PMID- 17037627
TI  - Equine histoplasmosis presenting as a tumor in the abdominal cavity.
AB  - A 3.5-year-old Thoroughbred mare presented at necropsy with a large mass at the
      root of the mesentery and multiple smaller mesenteric masses. The mucosa of the
      small intestine contained numerous raised nodules. Histologic examination
      revealed severe granulomatous mesenteric lymphadenitis and enteritis. Epithelioid
      macrophages and multinucleated giant cells frequently contained numerous
      intracytoplasmic yeast organisms, which were strongly positive on
      immunohistochemical staining when using a polyclonal antibody against Histoplasma
      spp. A diagnosis of abdominal histoplasmosis was made based on the gross,
      microscopic, and immunohistochemical findings.

PMID- 17037628
TI  - Hepatic yersiniosis in a cougar (Felis concolor).
AB  - A cougar (Felis concolor) was diagnosed with hepatic yersiniosis by bacterial
      culture and histopathology. The animal had a 2-week history of anorexia and
      jaundice before its death. Grossly, the liver exhibited caseo-necrotic foci.
      Histopathologically, there was necrotizing and suppurative hepatitis, with large
      numbers of intralesional gram-negative coccobacilli. Additional hepatic lesions
      included central vein thrombosis, lymphoplasmacytic portal hepatitis, and
      capsulitis. Yersinia pseudotuberculosis coccobacilli were isolated in pure
      culture from the hepatic lesions. Because the hepatic lesions in this animal
      resemble those of other zoonotic diseases, such as plague and tularemia,
      veterinarians and laboratory personnel who handle samples should take adequate
      safety precautions. This report is the first to describe the pathology associated
      with hepatic yersiniosis in a cougar.

PMID- 17037629
TI  - Lymphoma and Mycobacterium avium infection in a ferret (Mustela putorius furo).
AB  - A 6-year-old, neutered male ferret presented with weight loss. Radiography
      revealed an enlarged liver and other abdominal masses. The ferret was euthanized,
      and at necropsy, the stomach wall was thickened, mesenteric lymph nodes were
      enlarged, and the liver contained multifocal tan nodules. Histopathology
      confirmed lymphoma and granulomatous inflammation in all affected organs. Acid
      fast bacilli were present in the lesions and were confirmed to be Mycobacterium
      avium by PCR.

PMID- 17037630
TI  - DTC drug ads in the spotlight.

PMID- 17037631
TI  - Personal best. Reaching your potential.

PMID- 17037632
TI  - Economic credentialing: when hospitals play hard ball.

PMID- 17037633
TI  - What my patients taught me about healing.

PMID- 17037634
TI  - Breaking up is hard to do.

PMID- 17037635
TI  - Stop losing money! Code better.

PMID- 17037636
TI  - Can I pay a patient's bills?

PMID- 17037637
TI  - Hand-held dynamometry: adoption 1900-2005.
AB  - The purpose of this brief report is to describe the adoption of hand-held
      dynamometry, a procedure for documenting muscle strength. Between the early 1900s
      and the end of 2005, 478 research articles were published that documented use of
      hand-held dynamometry. The adoption of the procedure for research is consistent
      with the S-shaped curve described by Rogers. The extent to which hand-held
      dynamometry is used in clinical practice remains to be delineated.

PMID- 17037638
TI  - Reaction time reduction after parafoveal preview in a lexical decision task.
AB  - Time and the accuracy of a lexical decision performed on a letter string (either
      a word or nonword), presented foveally after a parafoveal preview displayed at 5
      degrees of eccentricity and 100 msec. duration were measured. Students of Padova
      University, 10 women and 7 men, ages 19 to 23 years were subjects. The hypothesis
      investigated was whether the facilitatory effect, a reduction in lexical decision
      time due to the parafoveal preview, was tied to global visual information
      acquired in the visual periphery during the preview presentation. In Exp. 1,
      eight subjects performed the task either with no preview (No Preview) or with a
      preview presented at 5 degrees eccentricity in two conditions, preview of the
      same foveal string (Preview-Letters) and preview of symbols ("x xx...") of the
      same length as the foveal string (Preview Symbols). In Exp. 2, 9 subjects
      performed the task with two preview conditions, No Preview and preview of the
      foveal string in uppercase letters at 5 degrees of eccentricity (Preview
      Uppercase). Analyses suggested the reduction in lexical decision time due to the
      Preview with respect to the No Preview condition is tied to global information
      extracted during parafoveal presentation. The reduction in lexical decision time
      depends on word texture, i.e., letters' identities and also word boundary, in
      addition to word length.

PMID- 17037640
TI  - Pain perception as a function of self-focused rumination.
AB  - Pain sensitivity and tolerance were studied using the cold-pressor technique. A 3
      independent groups design was employed using rumination as the independent
      variable. Group 1 was given a situation in which anger-related self-rumination
      was introduced. Group 2 was given a self-related rumination task in which anger
      was not induced. Group 3 received a rumination task not related to the self. In
      addition, the State-Trait Anger Expression Inventory was given prior to the
      experiment to test the hypothesis that ratings on the Anger-In subtest would
      correlate with pain sensitivity. In each group were 6 men and 6 women. Each
      participant took the anger and another inventory not relevant to the present
      study before the experiment. An anger measure was taken before and after the
      experiment for each group to see if the anger induction in Group 1 actually
      increased anger. There were no differences among the 3 groups on the second anger
      measure, so differences between Groups 1 and 2 could not be attributed to anger.
      A 1-way analysis of variance for 3 groups showed a strong main effect on pain
      tolerance but not pain sensitivity. Groups 1 and 2 were significantly more
      tolerant of pain than Group 3. The correlation of ratings on the Anger-In
      (internalized anger) subtest fell short of statistical significance with pain
      sensitivity and also was not significant for pain tolerance. Results were
      discussed in terms of the possibility that self-rumination may increase pain
      tolerance by requiring a greater cognitive load than nonself rumination.

PMID- 17037639
TI  - Grip strength and physical demand of previous occupation in a well-functioning
      cohort of Chinese older adults.
AB  - The grip strength of 214 independently ambulatory Chinese older adults (M age =
      75.1 +/- 7.0 yr.) was measured, and preliminary mean values presented. Their
      previous occupations were recorded, and the physical demands of those occupations
      in terms of oxygen consumption and work done were classified. Grip strength
      generally decreased across age groups. The physical demand of individuals'
      previous occupations had significant associations with grip strength, for
      example, participants who previously worked as construction site workers had a
      greater grip strength than those who worked previously as office workers.

PMID- 17037641
TI  - Sex differences and properties of the decreasing force during sustained static
      grip at various target forces.
AB  - The purpose of this study was to examine properties and sex differences of the
      decreasing force during sustained isometric grip using various target forces,
      50%, 75%, and 100% of maximal voluntary contraction (MVC), for 6 min.
      Participants were healthy, 15 men (height = 172.9 +/- 4.6 cm, body mass = 67.7 +/
      5.36 kg) and 15 women (height = 160.9 +/- 5.4 cm, body mass = 55.9 +/- 5.36 kg).
      The force decrease for target forces of 75% and 100% MVC was marked until 60 sec.
      from the onset of grip and then decreased gradually. On the other hand, the
      target force of 50% MVC was maintained for about 60 sec. and then decreased
      markedly until 100 sec. Differences in the decreasing force among target force
      levels was observed until 60 sec., and there were no significant differences of
      the time to decay to 20%, 30%, and 40% MVC. Namely, the time and force exertion
      reaching an almost steady state were considered to be almost the same at any
      target force. A sex difference on a parameter was found after 60 sec. or a
      decreasing force after 40% MVC, and women held it longer or higher than the men.
      However, the tendency was smaller in the latter phase of the steady state.

PMID- 17037642
TI  - Multidimensional voice program analysis in profoundly deaf children: quantifying
      frequency and amplitude control.
AB  - Characterization of the vocal profile of profoundly deaf children using an
      objective voice analysis was carried out in a university-based pediatric
      otolaryngology clinic. 21 persons ages 3.5 to 18 years were assessed. From each
      sustained phonation of the vowel /a/ the following acoustic variables were
      extracted: fundamental frequency (F0), jitter percentage, shimmer percentage,
      fundamental frequency variation (vF0), peak amplitude variation (vAM), and first,
      second, and third formant frequencies (F1, F2, F3). Mean F0 was 267.8 Hz and
      consistent with established normative data. Mean measurements of jitter (0.88%)
      and shimmer (3.5%) were also within normal limits. The notable feature of the
      acoustic analysis was a statistically significant elevation in vF0 (2.81%) and
      vAM (23.58%). With the exception of one subject, the F1, F2, and F3 formant
      frequencies were comparable to those for normal hearing children. Auditory
      deprivation results in poor long-term control of frequency and amplitude during
      sustained phonation. The inability to maintain a sustained phonation may
      represent the partial collapse of an internal model of voice and speech.

PMID- 17037643
TI  - Factors associated with perceived exertion and estimated time limit at lactate
      threshold.
AB  - The purpose was to identify the most predictive parameters for perceived exertion
      and estimated time limit responses at the velocity corresponding to the lactate
      concentration threshold. The former scale concerns the subject's current status
      (how hard he feels the exercise currently is) whereas the latter scale deals with
      a subjective prediction of how long the current exercise level can be maintained.
      Multiple regression equations were developed among physiological, psychological,
      nutritional, and individual parameters (subjects' characteristics and
      performances) as independent variables, and perceived exertion or estimated time
      limit as dependent variables. Independent variables were collected before or
      during an incremental running field test. 94 regional to national level athletes
      (47 endurance-trained runners, 11 sprinters, and 36 handball players)
      participated. Multiple stepwise regression showed that Rating of Perceived
      Exertion and Estimated Time Limit at the lactate threshold were mainly mediated
      by factors relative to the performance expressed in percentage of the maximal
      aerobic velocity. Secondary factors which contribute significantly as perceptual
      predictors were related to various classes of factors except for psychological
      factors.

PMID- 17037644
TI  - Is time limit at the minimum swimming velocity of VO2 max influenced by stroking
      parameters?
AB  - The aim of this study was to observe the relationship between time limit at the
      minimum velocity that elicits maximal oxygen consumption (TLim-v VO2 max) and
      stroke rate, stroke length, and stroke index. 13 men and 10 women, highly trained
      swimmers, performed an intermittent incremental test for v VO2 max assessment and
      an all-out swim to estimate TLim-v VO2 max. The mean +/- SD TLim-v VO2 max, v VO2
      max, stroke rate, stroke length, and stroke index values were 233.36 +/- 53.92
      sec., 1.40 +/- .06 meter/sec., 35.58 +/- 2.89 cycles/min., 2.39 +/- .22
      meter/cycle, and 3.36 +/- .41 meter2/(cycle x sec.), respectively. The
      correlation between TLim-v VO2 max and stroke rate was -.51 (p < .01), and values
      for TLim-v VO2 max with stroke length (r = .52, p < .01) and stroke index (r =
      .45, p < .05). These results seem to suggest that technical skill is a key factor
      in typical efforts requiring prolonged aerobic power.

PMID- 17037645
TI  - Dissociative alterations in body image among individuals reporting out-of-body
      experiences: a conceptual replication.
AB  - A conceptual replication of the link between self-reported dissociative
      alterations in body-image under experimental conditions and the reporting of
      prior out-of-body experiences in a recent data set was undertaken. Also examined
      was whether this relationship would hold for experiences reported during the
      experimental context and whether it is independent of self-reported New Age
      belief. Data from mostly undergraduates (N= 40; M age = 33.5, SD = 12.5; 27
      women) in a mirror-gazing study were retrospectively analyzed. The 9 individuals
      who reported prior out-of-body experiences, relative to those 31 who did not,
      exhibited significantly greater self-reported dissociative alterations in body
      image during the mirror-gazing task, even when the influence of scores on New Age
      belief was controlled for statistically. The same differential relationship was
      not found between 6 individuals who did and 34 who did not report out-of-body
      experiences during the task.

PMID- 17037646
TI  - Biomechanics Concept Inventory.
AB  - A third version of a biomechanics concept inventory was developed and
      administered to 41 kinesiology majors before and after an introductory
      biomechanics class to build a larger pool of questions for course evaluation. The
      test measured understanding of four prerequisite and eight competencies based on
      national standards. Mean and standard deviation normalized gain was 29% (21) of
      maximum possible improvement and was similar to previous versions of the test
      given to students at the same university. Biomechanics instructors can use
      questions from all versions of the Biomechanics Concept Inventory to customize
      tests for evaluating instructional techniques in biomechanics.

PMID- 17037647
TI  - Enabling a man with multiple disabilities and limited motor behavior to perform a
      functional task with help of microswitch technology.
AB  - This study evaluated the extent to which two microswitches used as interfaces
      would enable a man with multiple disabilities and limited motor behavior to
      operate an electric door opener at the entrance of the day center that he
      attended. Analysis showed the man (a) learned to use the two microswitches, (b)
      preferred the microswitch placed at his wheelchair's footrest (which also allowed
      more effective responding) over the microswitch placed at his wheelchair's
      armrest, and (c) maintained his positive performance at the 1- and 2-mo.
      postintervention checks. The results were discussed from a technical and
      practical standpoint and in terms of implications for the quality of life of
      persons with disabilities.

PMID- 17037649
TI  - Intensity and direction dimensions of competitive state anxiety: a time-to-event
      approach.
AB  - The purpose of the present study was to examine the temporally patterned changes
      in intensity and direction of competitive state anxiety prior to and during
      competition as well as correlations among intensity and direction on the
      Competitive State Anxiety Inventory-2D subscale scores. 99 athletes completed the
      inventory one day before and an hour before the competition, based on how they
      felt during that time, and 30 min. after the competition with reference to how
      they felt during the competition. Analysis indicated different temporal
      patterning in subscale scores prior to competition. Correlations were medium
      (.40) for Intensity and Direction dimensions. Significant differences were noted
      between scores of those classified as Facilitators and Debilitators on the
      Intensity dimension. The results support the multidimensional nature of
      competitive anxiety. Moreover, additional information lies in directional
      interpretation of competitive anxiety and self-confidence.

PMID- 17037648
TI  - Sex and eyedness in a sample of Turkish high school students.
AB  - The relationship of sex with eyedness was examined in 176 boys and 129 girls ages
      15 to 21 years (M = 16.9 yr., SD = 1.8) in Turkish high schools. Sex was
      significantly associated with handedness; the rate of left-handedness was 10.8%
      in boys and 2.3% in girls and was not related to eyedness. Rate of left-eyedness
      in the sample was 7.9% for boys and 8.5% for girls. One may wonder whether
      eyedness shows a reverse sex effect, less than handedness, but methods of
      measurement must be compared.

PMID- 17037650
TI  - Form of athletic exercise, school environment, and sex in development of high
      school students' sportsmanship.
AB  - To examine the influence of form of athletic exercise, school environment, and
      sex in the sportsmanship of high school students, 158 boys and 197 girls, ages 15
      to 18 years (M = 16.0, SD = .7) in physical education at school, recreational
      sports, and competitive sports at three schools were examined. Analysis of
      students' responses on the Multidimensional Sportspersonship Orientation Scale
      indicated the form of athletic exercise, the school environment, and sex were
      related to their sportsmanship. These factors should be considered in planning
      programs on moral education.

PMID- 17037651
TI  - Reliability and factor structure of the Finnish version of the Sport Imagery
      Questionnaire.
AB  - The aim of this study was to examine the reliability and factor structure of the
      Finnish version of the Sport Imagery Questionnaire, a measure which examines
      cognitive and motivational functions of imagery. The final sample comprised 231
      participants drawn from 34 sports and ranging in age from 14 to 49 years (M =
      20.9, SD = 5.8). Internal consistency and confirmatory factor analyses were
      undertaken to evaluate the reliability and factorial validity of the scale. Fit
      indices and modification data generated from examining the 30-item five-factor
      model were equivocal, suggesting minor amendment and recategorization of several
      items rather than major adjustment to the proposed latent factor structure.
      Cronbach coefficients alpha indicated the scale is reliable. Overall, these
      results provide positive additional support for the claim that the Sport Imagery
      Questionnaire has a reproducible factor structure and is a reliable test for
      measuring imagery use in Finnish athletes.

PMID- 17037652
TI  - Attitudes toward and approaches to learning first-year university mathematics.
AB  - This study examined the relationship for 180 undergraduate students enrolled in a
      first-year university calculus course between attitudes toward mathematics and
      approaches to learning mathematics using the Mathematics Attitude Scale and the
      Approaches to Learning Mathematics Questionnaire, respectively. Regression
      analyses indicated that scores for the Mathematics Attitude Scale were negatively
      related to scores for the Surface Approach and accounted for 10.4% of the
      variance and scores for the Mathematics Attitude Scale were positively related to
      scores for the Deep Approach to learning mathematics and accounted for 31.7% of
      the variance.

PMID- 17037653
TI  - Digit Symbol Substitution test performance: sex differences in a Hebrew-readers'
      health population.
AB  - The Digit Symbol Substitution test is simple to administer and sensitive to
      individual differences related to cognitive performance. The present study
      evaluated sex-related differences in performance by a Hebrew reading sample. The
      test was administered to 275 men and 252 women (age range: 20-44 years). Hebrew
      women significantly scored higher than the men. Means which increased during four
      consecutive 30-sec. time periods of performance, was significantly greater for
      the women than the men. This finding indicates women were more effective on this
      pair-associated learning task than men.

PMID- 17037654
TI  - Contact sports, moral functioning and planned behaviour theory.
AB  - The goal was to test the psychometric properties of the Moral Functioning Scale
      in a Greek athletic context, and to investigate any possible relation between
      moral functioning and planned behaviour. The sample comprised 384 athletes, 103
      from the sport of football (soccer), 97 from basketball, and 184 from water polo.
      To measure moral functioning the researchers used a scale developed by Gibbons,
      Ebbeck, and Weiss. Planned Behaviour was assessed with a questionnaire based on
      Planned Behaviour Theory. Hierarchical regression analysis indicated strong
      association for Attitudes, Intention, Role Identity, and Perceived Behavioural
      Control with the four dilemmas of the moral functioning scale. The moral
      reasoning measure is a promising tool for measuring athletes' moral dilemmas in
      Greece.

PMID- 17037655
TI  - Development of eating behavior by Japanese toddlers in a nursery school: relation
      to independent walking.
AB  - The eating behavior of 32 toddlers in a nursery school at 10, 12, and 14 months
      old was observed in relation to the age at onset of independent walking. With
      increasing age, the frequency at which the toddlers ate food given by a teacher
      decreased, and the frequency at which the toddlers ate by themselves increased.
      The toddlers who started walking earlier also advanced faster in the development
      of eating behavior. The time when the frequency of eating by oneself surpassed
      the frequency of passive eating coincided with the time when the toddlers started
      walking.

PMID- 17037656
TI  - Soccer players' muscular imbalances: restoration with an isokinetic strength
      training program.
AB  - The aim of the study was to investigate the effect of a muscular training program
      on soccer players' performance which initially appeared imbalanced or bilaterally
      asymmetrical. During the preparation period, 35 soccer players performed an
      isokinetic measurement of knee flexors and extensors (60 degrees(-1) and 180
      degrees sec.(-1)). 15 of these had muscular imbalances or deficits and followed a
      specific isokinetic training program for 2 mo., 3 times per week. After the
      completion of the isokinetic training program, the 35 players underwent the same
      isokinetic test. Significant differences were noted between the pre- and
      posttraining measures at both angular velocities in peak torque values, in
      differences from one limb to the other, and in peak torque ratios for flexors and
      extensors. Consequently, the application of this specific isokinetic training
      program can restore imbalances in knee muscle strength efficiently.

PMID- 17037657
TI  - Effect of static visual acuity on dynamic visual acuity: a pilot study.
AB  - The aim of this pilot study was to evaluate whether dynamic visual acuity changes
      with or without refractive correction. 42 healthy enrolled subjects with normal
      vision were divided into two age-matched groups. In Group A, dynamic visual
      acuity was measured first with the refractive error fully corrected and then
      without. In Group B, dynamic visual acuity measurements were taken in the reverse
      order of that performed by Group A. The measurements were binocularly performed
      five times using free-head viewing after dynamic visual acuity values were
      stable. Significant changes in dynamic visual acuity (static visual acuity 20/20
      vs 12/20) were observed in both Group A (171.6 +/- 36.0 deg./sec. vs 151.8 +/-
      39.6 deg./sec., Wilcoxon test, p < .001) and Group B (169.8 +/- 30.0 deg./sec. vs
      151.2 +/- 36.0 deg./sec., Wilcoxon test, p < .001). The interaction was
      significant (F1.20 = 8.12, p = .009). These results indicated that refractive
      correction affected dynamic visual acuity.

PMID- 17037658
TI  - Interactive decision-making: effects of consultation before personal decisions on
      postdecision consolidation.
AB  - Pre- and postdecision processes were studied in triads of participants, dyads of
      participants, and for individual decision-makers in two experiment (N = 57 and
      50). Participants were students volunteering to take part in the study (21 men
      and 36 women with a mean age of 24 yr. and 25 men and 25 women with a mean age of
      27 yr.). The purpose was to examine how much interactive versus individual social
      interaction (consultation with others before making a personal decision) affects
      postdecision consolidation. Predecision differentiation and postdecision
      consolidation have been defined as attractiveness changes over time in favour of
      the chosen alternative. Participants were coded into three categories
      (noncompensatory, compensatory, and nonclassified) according to their different
      decision strategies. For Exp. 1, postdecision consolidation effects were
      significant for participants who used a noncompensatory (no comparisons across
      attributes) decision strategy. For Exp. 2, postdecision consolidation effects
      were significant for participants who made a personal decision but not those who
      made an interactive decision. The differing results in these two experiments were
      discussed.

PMID- 17037659
TI  - Relation of age and passive properties of an ankle dorsiflexion stretch to the
      timed one-leg stance test in older women.
AB  - 26 older women (aged 65 to 89 years) participated in this study, which examined
      the relationship of age and passive properties of a dorsiflexion stretch of the
      calf muscle-tendon unit with one-leg stance times. Age was negatively correlated
      with the time stance (r = -.75). The maximal passive dorsiflexion angle, length
      extensibility, maximal passive dorsiflexion torque, and the area under the
      passive curve (total passive elastic energy) were all positively correlated with
      the stance time (range: r = .49-.69). A multiple regression analysis indicated
      age was the best predictor of the times. Age and the maximal passive dorsiflexion
      angle together accounting for 71% of the variance in the time (R = .84, R(2) =
      .71). The addition of the remaining passive measurements did not improve the
      variance accounted for in the one-leg stance time. The results indicated that the
      maximal ankle dorsiflexion range of motion may be important for one-leg standing
      balance of older women. Accordingly, stretching exercises designed to increase
      the maximal dorsiflexion angle may have a role for maintaining or improving their
      standing balance.

PMID- 17037660
TI  - Effect of an auditory training program on reading, phoneme awareness, and
      language.
AB  - This investigation examined the effect of an auditory training program, Fast
      ForWord-Language, with 26 children ages 7 to 10 years. As two subgroups based on
      reading ability, all children received 6 wk. of intervention. Thresholds for
      three conditions of backward masking were obtained pre- and postintervention, and
      6 mo. afterward. Immediately following the intervention period, backward masking
      thresholds improved for all backward masking conditions. Participants also showed
      increases in language skills and in phoneme awareness but not in reading skills.
      Six months after intervention, there were improvements in thresholds for backward
      masking but no improvements in language or reading skills for either group. This
      study calls into question the efficacy of an intensive auditory training program
      to improve reading skills.

PMID- 17037661
TI  - Young adult drivers' sensitivity to changes in speed and driving mode in a simple
      vehicle simulator.
AB  - The study was done to check replication of changes in sensitivity with a simple
      simulator as had been obtained in an experiment using the real road situation.
      Another purpose was to control simulator sickness which could have confounded
      data from testing with a simulator or in actual driving. Sensitivity of the
      drivers (72 healthy young adults, M age = 24 yr., SD = 5) while performing the
      driving task was measured in terms of subjective ratings of simulator sickness
      and affect, and physiological measures (i.e., galvanic skin responses and skin
      temperature) at different driving speeds and in driving mode conditions, using a
      simple vehicle simulator. Analysis showed measures of drivers' state, including
      simulator sickness, physiological indices, and subjective reports, increased with
      driving speed (30 --> 90 -->120 km/hr.) and driving mode change from the regular
      speed to sudden increasing to sudden decreasing speeds. Particularly, the results
      suggest that the increased autonomic nervous activation induces increase of rated
      simulator sickness. Based upon the same tendency in change of the simulator
      sickness and physiological state with driving speed and driving mode conditions,
      it was concluded that, if the results obtained from the simulator experiment can
      be generalized to the real situation, the simulator sickness must be considered a
      confounding factor. The results also suggest that the changes in human
      sensitivity are dependent upon aspects related to speed of a vehicle and driving
      mode.

PMID- 17037662
TI  - Smiling faces rated more feminine than serious faces in Japan.
AB  - It has been reported that women and girls smile more frequently and more
      effectively than men and boys. It is expected that this correlation between
      femaleness and smiling affects the processing of faces, and consequently, smiling
      faces may be perceived to be more feminine. Participants viewed 30 photographs
      featuring smiling and serious facial expressions of both male and female subjects
      and rated them for femininity or masculinity. The result indicated that smiling
      faces significantly more frequently gave the impression of being more feminine.
      The interaction between the sex of the faces and their expression was not
      significant.

PMID- 17037663
TI  - Reference values for the five-repetition sit-to-stand test: a descriptive meta
      analysis of data from elders.
AB  - This meta-analysis was conducted to generate normative values for the 5
      repetition sit-to-stand (STS) test suitable for application to individuals at
      least 60 years of age. A thorough review of the literature yielded 13 papers (14
      studies) relevant to this purpose. After the exclusion of potentially
      unrepresentative data, meta-analysis of these 13 papers indicated that judgments
      about normal performance should be based on age. Analysis demonstrated that
      individuals with times for 5 repetitions of this test exceeding the following can
      be considered to have worse than average performance: 11.4 sec (60 to 69 years),
      12.6 sec. (70 to 79 years), and 14.8 sec. (80 to 89 years).

PMID- 17037664
TI  - Writing program with word prediction for a young man with multiple disabilities:
      a preliminary assessment.
AB  - This study assessed a writing program with word prediction, which completed the
      writing of a word and spoke it out only when there was certainty that such a word
      was the correct one. The assessment was carried out with a young man with
      multiple disabilities, who typically used a word-processing program without word
      prediction. The two programs were compared on the time required by the
      participant for writing general sentences, through a social validation
      assessment, and eventually a check on the participant's preference. Analysis
      showed the program with word prediction was significantly more effective in terms
      of the writing time, which was halved, and was deemed preferable by 40 raters
      (psychology students) involved in the social validation assessment and by the
      participant himself. Implications of the findings are discussed.

PMID- 17037665
TI  - Assessments of young soccer players: a holistic approach.
AB  - Use of scores on a single test of endurance which discriminates potentially
      talented under-age players' performance is insufficient for prediction of later
      performance, but such data could be useful when considered with other test
      scores.

PMID- 17037666
TI  - Comparison of isokinetic peak force and power in adults with partial and total
      blindness.
AB  - For many populations the ability to move efficiently is compromised by an
      impaired muscular functioning. Strength development is necessary to overcome the
      effects of gravity to maintain posture and generate movement responses for
      mobility. The strength and power capabilities of individuals with total blindness
      (n = 12) were compared to those with partial vision (n = 12) to evaluate effects
      of vision on performance. Results indicate that (1) no significant differences
      were apparent between total blindness and partial vision, (2) significant sex
      differences were evident in each group, and (3) better performance was apparent
      at lower velocities. It was concluded that physical performance in individuals
      with blindness and partial vision are equally deficient.

PMID- 17037667
TI  - Relations of perceived bodily changes with actual changes and changes in mood in
      obese women initiating an exercise and weight-loss program.
AB  - Significant relationships were found between mean difference scores for body
      satisfaction and mood (rs = /.42 to .54/) for obese women (N = 50) beginning
      exercise programs for weight loss. No significant relationships were found
      between self-reported body satisfaction and measures of bodily changes. After
      replication, implications for theory and treatment were discussed.

PMID- 17037668
TI  - Contextual interference effect on acquisition and retention of pistol-shooting
      skills.
AB  - The effects of contextual interference on learning pistol-shooting skills in a
      natural training environment were examined. The shooting skills consisted of
      three "stages" with different requirements for the skill variations commonly used
      in the field. 12 participants were randomly assigned into one of two practice
      conditions, blocked vs serial. Following a 20-min. safety and skill instructional
      session, Blocked group practiced 10 trials in a row at each stage, while Serial
      group performed 5 trials in a row for each of the three stages and then repeated
      the cycle. Both groups completed a total of 30 practice trials over the three
      stages. A 10-min. rest interval was provided prior to a retention test which
      included 9 trials (3 trials at each stage in a blocked format). Results based on
      the data of Stage III, the most complex skill among the three stages, showed a
      pattern consistent with previous findings that practicing in the serial schedule
      depressed performance during initial training but maintained the performance
      better at retention, relative to the blocked practice.

PMID- 17037669
TI  - Perceived body size affected by garment and body mass index.
AB  - This study investigated the effect of garment size on perceived body size. The
      perceived body sizes of nine Chinese men, with Body Mass Index between 17.0 and
      37.1 kg/m(2), wearing five sizes of white T-shirts were assessed using Thompson
      and Gray's Nine-figural Scale. Garment sizes on perceived body sizes were
      different for those of different Body Mass Index. A backpropagation neural net
      model was used to model the nonlinear relationship between the perceived body
      size and the body's BMI, body chest girth, and garment ease (difference between
      garment and body chest girth). When the BMI was less than 20, wearing larger
      sized T-shirts tended to increase perceived body size. For large chest sizes and
      for taller persons (BMI of 20 to 28) large garments made the wearer look thinner.
      However, for small persons (BMI of 20 to 28) effect of garment size was
      relatively small. Obese persons (BMI of > 28), wearing garments too tight or too
      loose were perceived as larger. Minimum perceived body size was found for garment
      ease of 2 to 3 cm.

PMID- 17037670
TI  - Tapping speed asymmetry in drummers for single-hand tapping with a stick.
AB  - The purpose of this study was to investigate tapping speed asymmetry in 13 right
      handed drummers and 13 right-handed nondrummers. The participants executed single
      hand tapping with a stick as fast as possible for 10 sec. with the left and right
      hand. There was no significant difference in the tapping speed of the right hand
      between the drummers and the nondrummers, whereas in the left hand, the drummers
      tapped significantly faster than the nondrummers. Drummers showed less tapping
      speed asymmetry than nondrummers. These results suggest that the tapping speed of
      the nonpreferred hand progressed nearly to the level of the preferred hand
      through daily drum training.

PMID- 17037671
TI  - Goal setting in acquisition of a volleyball skill late in motor learning.
AB  - To examine the effects of different types of goal setting on motor skill
      acquisition during advanced stages of learning. 44 female volleyball players were
      tested in four experimental training groups with generic goals, specific long
      term goals, specific short-term goals, and as a control group. This study's
      pretest, training, and retention test phases used performance of a volleyball
      dig/forearm pass oriented to a target. Analyses yielded no significant
      differences among groups, although performance increased from pre- to retention
      test.

PMID- 17037672
TI  - Asymmetric recognition of pictures of cats as a function of age in 4-, 5-, and 6
      year-old children.
AB  - In the present study it was investigated whether children recognized deletions
      more accurately than additions in pictures of animate objects as a function of
      age between 4 and 6 years. Children, presented pictures of cats with features
      added to or deleted from the original pictures, judged whether the pictures were
      the same or different as those in a test of recognition. Analysis showed both 5
      yr.-olds and 6-yr.olds discovered deletions more accurately than additions. This
      asymmetric effect is in accord with that of adults, with whom the same stimuli
      were used in earlier research, but are contrary to previous studies in which
      additions were recognized more accurately than deletions when inanimate objects
      were stimuli. Asymmetric effects, that is, greater recognition accuracy for
      deletions may be related to children's being uncomfortable about modified
      pictures of animals.

PMID- 17037673
TI  - Music and physical activity in psychological well-being.
AB  - The present study was designed to examine the effects of listening to music
      during exercise of moderate intensity on mood, state anxiety, and time to
      exhaustion as well as to evaluate sex differences in 27 physically active (14
      men, 13 women) subjects between the ages of 20 and 30 years. Participants
      completed the Profile of Mood States and the State Anxiety Inventory before and
      after treadmill running in Music and No music conditions. Music and No Music
      conditions were randomly assigned, and participants exercised at 75% of their
      Heart Rate Reserve until voluntary exhaustion. Analysis indicated participants
      reported statistically significant mean changes on Tension, Depression, Fatigue,
      Confusion, and State Anxiety. However, the findings for emotions yielded no
      significant effect of music, except findings suggested that women, but not men,
      reported greater mean Fatigue after exercising in the presence of music than in
      its absence. Also, there was a statistically significant finding suggesting that
      women exercised longer with music than without.

PMID- 17037674
TI  - Attitudes toward physical education classes of primary school students in Turkey.
AB  - The purposes of this study were to report an investigation of attitudes toward
      physical education in a sample of primary school students and examine the
      predictive influence of students' sex, grades in physical education classes, and
      parents' education and socioeconomic status on students' attitudes. Participants,
      963 (474 girls and 489 boys) primary school students from Grades 6 (12.7%), 7
      (10.3%) and 8 (77%), completed the Wear Attitude Inventory. Analysis indicated
      students had positive scores on General Attitudes rather than on Social,
      Emotional, and Physical Attitudes. In addition, girls (M = 32.6, SD = 3.9) had
      more positive General Attitudes than boys (M = 32.0, SD = 4.6). Also, students'
      grades in physical education classes were statistically significantly related to
      their Attitudes toward physical education (Wilks lambda, F1,1110 = 2.88, p <
      .05). However, parents' education and socioeconomic status were not. One may
      infer that ways of encouraging more favorable attitudes might be planned.

PMID- 17037675
TI  - Effects of religion and type of religious internalization on the mental health of
      Iranian adolescents.
AB  - This study was designed to assess the effects of religion and two types of
      religious internalization on the mental health of Iranian adolescents. High
      school students (82 Moslem and 37 Christian) were selected randomly from four
      high schools in Shiraz and completed the Religious Self-regulation Questionnaire
      and the General Health Questionnaire. Analysis showed that main effects of types
      of religious internalization measured on four subscales of the General Health
      Questionnaire were significant. Religion was significantly associated only with
      somatic symptoms. For other scales no main effects of religion, types of
      religious internalization, or their interactions were significant.

PMID- 17037677
TI  - [Minimally invasive surgery of the pituitary and the sellar region].
AB  - INTRODUCTION: New minimal invasive neurosurgical approaches for the treatment of
      diseases in the sellar and perisellar regions (superciliary and paraseptal
      approach, perioperative ACTH measurements, application of endoscopes and
      neuronavigation) were introduced by the author. The modified surgical techniques
      were applied by the author successfully in the treatment of more than 1000 cases,
      of which the data of 746 patients were analysed and the results are presented.
      METHODS AND RESULTS: The results of the clinical studies concerning superciliary
      and paraseptal approaches were as follows: length of the operations and, loss of
      blood were decreased, the patients needed shorter anesthesia and the treatment
      cost became lower. The approaches were performed without hair cutting with
      excellent cosmetic results leading to easier resocialisation of the patients. In
      the group of the patients operated on through the superciliary approach
      postoperative vasospasm developed in significantly lower rate, the number of days
      spent in the intensive care unit decreased and the rate of patients on discharge
      in good clinical condition were higher. The study on perioperative plasma ACTH
      simultaneous measurements with rapid and standard methods revealed first in the
      literature that, during anaesthesia in patients with ACTH producing adenoma the
      plasma ACTH level changed individually. There was no difference between arterial
      and venous plasma ACTH concentration in the same patient and the ACTH
      concentration in the bleedings from the peripituitary bony structures are
      individually variable, representing the network of the venous outflow of the
      pituitary. The decrease in the plasma ACTH concentrations in the peripheral
      venous samples two hours after operation and next morning proved the radical
      removal of the adenoma. The differences between concentrations in the left and
      right sides indicate the intrapituitary lateralization of the adenoma. The study
      on the usefulness of neuroendoscopy and neuronavigation in the author's hand
      revealed the advantages and disadvantages of these new neurosurgical instruments.
      CONCLUSIONS: With the advent of the minimal invasive methods in surgery of the
      pituitary and the sellar region the mortality end the morbidity of the operations
      decreased.

PMID- 17037676
TI  - [Expression of ZEBRA protein of Epstein-Barr virus in Hungarian patients with
      Hodgkin lymphoma: latent or lytic cycle?].
AB  - INTRODUCTION: Epstein-Barr virus is a ubiquitous human herpes virus in the
      Hungarian population. The virus is associated with an increasing number of
      lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of
      the virus to establish life-long persistent infection and induce growth
      transformation is related to the viral proteins that are variously expressed in
      both normal and malignant cells. Although the presence of ZEBRA protein induces
      lytic cycle, some lymphoma cases show this protein expression. AIM: In our
      present study we investigated the frequency of expression of ZEBRA protein in
      Hungarian patients with Hodgkin lymphoma associated with Epstein-Barr virus
      infection. The authors wanted to clarify whether this expression is specific to
      latency type II or occurs in some non-Hodgkin lymphoma cases with latency type
      III as well. Does the expression of ZEBRA protein have any effect on therapeutic
      response and survival rate of the patients? METHOD: 109 HL and 59 NHL were
      studied for the presence of the virus in the tumor and for expression of the
      latency proteins and ZEBRA by immunohistochemistry. RESULTS: 25 samples were
      evaluated successfully for ZEBRA of the 47 LMP1 positive HL samples. We detected
      the weak expression of ZEBRA protein in 13 of the 25 LMP1 positive Hodgkin
      lymphoma cases and in 6 of the 18 LMP1 positive non-Hodgkin lymphoma samples. The
      authors could not find correlation between the expression of ZEBRA protein and
      the type of latency. During the followed 120 months the total survival of
      patients with ZEBRA positivity proved to be significantly shorter as compared to
      that of ZEBRA negative cases. The authors could not find significant difference
      in the uneventful survival of these two groups. CONCLUSION: In the examined group
      of patients the ZEBRA positivity associated with a poor prognosis of the disease.
      Besides this relatively small number of cases, additional extensive studies are
      needed to conclude our observation. Elucidation of the switching mechanisms by
      which Epstein-Barr virus induces lytic cycle may provide an efficacious
      therapeutic approach to the EBV-related malignancies.

PMID- 17037678
TI  - [Obstructive sleep apnea and cardiovascular disease].
AB  - Sleep-related breathing disorders are prevalent in the general population and are
      associated with a wide range of cardiovascular diseases. Obstructive sleep apnea
      is the most common form of sleep-related breathing disorders and is characterized
      by repetitive episodes of partial or complete upper airway obstruction, followed
      by oxygen-desaturation and arousals. These apneic events disrupt normal sleep and
      lead to various acute and chronic cardiovascular consequences. The current
      standard treatment with nasal continuous positive airway pressure eliminates
      apneas, improves sleep fragmentation and prevents consequent hemodynamic changes
      during sleep. Every patient with hypertension, obesity or heart disease should be
      asked routinely about symptoms of sleep apnea and referred for a sleep study if
      necessary.

PMID- 17037679
TI  - [Fetal ischaemic brain injury in the second trimester of pregnancy].
AB  - Based on clinical, epidemiologic, and experimental studies, the aetiology of
      white matter damage, specially periventricular leukomalacia (PVL), is
      multifactorial and involves pre- and perinatal factors. Each of these factors is
      supposed to be a major precursor for neurological and intellectual impairment,
      and cerebral palsy (CP) in later life. Antenatal rather than intrapartum factors
      are now emerging as the major determinants of cerebral palsy. In this case report
      maternal trauma, benign tumour, severe anaemia and fetal cerebral vascular
      malformation are supposed as causative factors in intrauterine periventricular
      leukomalacia resulting from hypoxic-ischaemic injury.

PMID- 17037680
TI  - [Alopecia areata caused by extreme solar abuse].
AB  - The Authors present a female patient who suffered from alopecia areata caused by
      extreme solar abuse. Biological effects of ionizing radiation, the damages by
      free radicals and protection against oxidative damage are summarized. The main
      forms and risk factors of UV-radiation, skin damages by UV-light as well as the
      pathogenesis of the alopecia areata are reviewed.

PMID- 17037681
TI  - [Prostate cancer].

PMID- 17037682
TI  - Fundamentals of research ethics--international and regional perspectives: welcome
      address.

PMID- 17037683
TI  - "To eat an elephant".

PMID- 17037684
TI  - Research ethics: challenges in the Eastern Mediterranean Region.
AB  - The foundations of ethical principles in the Eastern Mediterranean Region can be
      found within the 3 major religions of the Region; Judaism, Christianity and
      Islam. Today, there are numerous ethical issues that have emerged as result of
      the technological advances of the 20th century and this paper addresses some of
      those related to biomedical research. The Islamic principles in relation to
      medicine and biomedical research are described, and in particular research
      involving human subjects. The paper also outlines the endeavours being made by
      the Islamic Organization for Medical Sciences to address such issues and draw up
      recommendations and rulings.

PMID- 17037685
TI  - Bioethics: a search for moral diversity.
AB  - The concept of global, Asian and Chinese bioethics are discussed in this paper
      and the difficulty in applying universal bioethics within different cultures and
      countries is addressed. The traditional beliefs and values in China are described
      with particular reference to medicine, and the implications for bioethics and
      research ethics within the country are considered.

PMID- 17037686
TI  - Research and developing countries: hopes and hypes.
AB  - The paper outlines the universal problem of ensuring ethical practices in human
      subject research, and focuses on specific difficulties faced in the developing
      world with particular reference to Pakistan. It discusses the influence of
      traditional and hierarchical social norms of physician-patient relationships in
      heightening these problems. Two emerging issues of specific concern in Pakistan
      are described: an exponential rise in multinational clinical drug trials, and
      commercial ventures offering unproven stem cell "therapy" for all kinds of
      diseases. The importance of introducing ethical practices in research within the
      context of local cultural and socioeconomic realities is highlighted.

PMID- 17037687
TI  - What is owed to the community before, during and following research: an ethical
      dialogue.
AB  - The paper briefly outlines some of the ethical issues involved in community-based
      research particularly in developing countries. It focuses on informed consent,
      confidentially and the obligations to the community or its members who
      participate in the study. Most ethical guidelines are focused on the individual
      participants. Yet increasingly the community may be the unit of study. More
      attention will need to be directed towards developing guidelines for community
      based research.

PMID- 17037688
TI  - Pharmaceutical research: paradox, challenge or dilemma?
AB  - A great deal of pharmaceutical research is nowadays carried out in developing
      countries such as Pakistan. Is it, however, beneficial for the country and the
      participants, often the poorly educated and illiterate? Pharmaceutical research
      in Pakistan can bring benefits to both patients and country. Promotion of good
      clinical practice and the development of national guidelines are advocated.
      Government and industry both have a role to play to maintain the right balance.

PMID- 17037689
TI  - Informed consent: views from Karachi.
AB  - Little is known about the public's perceptions about the process of obtaining
      informed consent for participation in medical research. A study was made of the
      views of patients, their attendants, parents, schoolteachers and office workers
      living in Karachi, Pakistan. Participants felt that informed consent was an
      important step in recruiting research participants but many felt that it was a
      trust-based process not requiring proper documentation. For recruiting women,
      both men and women believed it was important to approach women through their
      husbands and fathers. When there was a conflict with the opinions of family
      leaders, it was clear that the male participants' opinion was valued more than
      that of the female participants by both men and women.

PMID- 17037690
TI  - Bioethics activities in India.
AB  - The Indian Council of Medical Research formulates, coordinates and promotes
      biomedical research in India. In 1980, they formulated the first national ethical
      guidelines. They offer a number of different training programmes, from 1 day to 6
      months. The council is developing a core curriculum for teaching bioethics, which
      would be applied uniformly in medical schools throughout the country. Drug
      development and ethics is also important in India, particularly now that the
      local pharmaceutical industry is expanding and so many drugs trials are
      outsourced to the country. The council is also very active in encouraging the
      development of ethics review committees.

PMID- 17037691
TI  - Regional perspectives in research ethics: a report from Bangladesh.
AB  - Health research in Bangladesh is increasing and hence there is a need to consider
      the ethical issues with regard such research. This paper describes the measures
      being taken in Bangladesh to address research ethics, such as the bioethics
      educational programmes and the ethics review committees functioning within the
      country. The role and work of the Central Ethics Review Committee and the
      regulatory guidelines are outlined. The paper also discusses the situation
      regarding research ethics within the South Asia region.

PMID- 17037692
TI  - Bioethics in Sri Lanka.
AB  - Bioethics took off slowly in Sri Lanka, but now there are ethics review
      committees in many medical schools and national organizations. All medical
      schools teach some medical ethics but there are not enough trained teachers.
      There are no national guidelines on research ethics. The Forum for Research and
      Development was formed with the aim of building a new ethical research culture.
      The bioethics initiative includes: awareness-raising; education activities and
      capacity building; advocacy; and the development of policy guidelines. We aim to
      raise awareness in the scientific community and the general public on ethical,
      legal and social principles guiding the responsible conduct of research.

PMID- 17037694
TI  - Epidemiology of malaria and predictions of retransmission in Babylon Governorate,
      Iraq.
AB  - After the 1997-98 malaria epidemic in Babylon governorate, Iraq, malaria
      transmission in this area was successfully interrupted. A parasitological survey
      in 2002 identified no malaria cases but an entomological survey found both
      Anopheles stephensi and A. pulcherrimus in high densities. The highest density
      was recorded in September and the lowest in December and January. Despite the
      high density of Anopheles, no parasite sporozoites or oocysts were found in
      dissected mosquitoes. Nevertheless, malaria transmission could recur if A.
      stephensi indoor resting density exceeds the critical threshold and imported
      malaria cases are not monitored.

PMID- 17037693
TI  - Prevalence of HCV/HIV co-infection among haemophilia patients in Baghdad.
AB  - To estimate the seroprevalence of HCV infection among HIV-infected haemophiliacs
      and to demonstrate the most prevalent HCV genotype, 47 HIV-infected haemophilia
      patients were screened for anti-HCV antibodies. By performing polymerase chain
      reaction and DNA enzyme immunoassay, HCV-RNA was detected with subsequent
      genotyping. Seroprevalence of anti-HCV antibodies was 66.0%. Of 31 HCV/HIV co
      infected patients, 21 (67.7%) had no history of blood transfusion. We detected 4
      HCV genotypes: 1a, 1b, 4 and 4 mixed with 3a, HCV-1b being the most frequent.
      Contaminated factor VIII (clotting factor) could be responsible for disease
      acquisition.

PMID- 17037695
TI  - Environmental mycobacteria in areas of high and low tuberculosis prevalence in
      the Islamic Republic of Iran.
AB  - This research compared the numbers and types of different Mycobacterium species
      in soil samples taken from 2 areas of Golestan province, Islamic Republic of
      Iran, 1 with a high prevalence of tuberculosis and 1 with a low prevalence. From
      220 samples, 91 grew positive cultures (41.4%) and 161 different strains were
      diagnosed. The most common species isolated were Mycobacterium fortuitum, M.
      flavescens and M. chelonae. The frequencies of environmental Mycobacterium in the
      low-prevalence area were much higher than in the high-prevalence area, perhaps
      due to different environmental fac-

PMID- 17037696
TI  - Antimicrobial effectiveness of furazolidone against metronidazole-resistant
      strains of Helicobacter pylori.
AB  - The occurrence of strains resistant to metronidazole is causing failure of the 4
      drug regimen for eradication of Helicobacter pylori in the Islamic Republic of
      Iran. This study compared the in vitro efficacy of furazolidone with
      metronidazole, clarithromycin, amoxicillin and tetracycline in 70 H. pylori
      isolates from dyspeptic patients. Of the isolates, 33% were resistant to
      metronidazole but all were susceptible to furazolidone. Furazolidone could be
      considered as an appropriate substitute for metronidazole for H. pylori
      infections.

PMID- 17037697
TI  - Evaluation of rK39 strip test for the diagnosis of visceral leishmaniasis in
      infants.
AB  - This study estimated the sensitivity and specificity of the rK39 strip test
      compared with the immunofluorescent antibody test and microscopy of bone marrow
      aspirate smears (the gold standard) in 47 children with suspected visceral
      leishmaniasis. A control group of children with other diagnoses (tuberculosis,
      toxoplasmosis, systemic lupus erythematosus, malaria or cutaneous leishmaniasis)
      were also tested to check false positive results. The sensitivity and specificity
      of the strip test were 82.4% and 100% and that of immunofluorescent antibody were
      100% and 92.7%. The rK39 strip test is reliable where there is no access to
      laboratory facilities.

PMID- 17037698
TI  - Hajj-associated acute respiratory infection among hajjis from Riyadh.
AB  - A prospective cohort study was conducted to estimate the incidence of acute
      respiratory infections (ARI) among hajjis registered at primary health care
      centres of Riyadh. Out of 1027 hajjis, 39.8% developed symptoms of ARI. The
      incidence of ARI was not statistically significantly associated with age, sex,
      educational status or smoking. The risk of illness was significantly higher among
      diabetics, hajjis who stayed longer in the hajj area and who prayed at Namera
      mosque. Use of a facemask by men, but not use of a facecover by women, was a
      significant protective factor against ARI.

PMID- 17037699
TI  - Evaluation of the 10th External Quality Assessment Scheme results in clinical
      microbiology laboratories in Tehran and districts.
AB  - We evaluated the performance of microbiology laboratories in the 10th run of the
      external quality assessment scheme (EQAS) in Tehran and districts. Each
      laboratory was sent 2 species of bacteria for identification. Of the 487
      laboratories that participated, 437 returned their findings. While 77.0% and
      69.9% correctly identified Staphylococcus saprophyticus and Citrobacter freundii
      respectively, only 29.8% correctly identified Acinetobacter baumanii, 25.3%
      identified Enterococcus faecalis and 35.6% identified Enterobacter agglomerans.
      However 78.7% and 79.5% of the laboratories reported correct -results for
      susceptibility testing for S. saprophyticus and C. freundii respectively.

PMID- 17037701
TI  - Differential aspects of consultation-liaison psychiatry in a Saudi hospital. II:
      knowledge and attitudes of physicians and patients.
AB  - To assess the attitude and knowledge of physicians and patients towards
      psychiatry, we asked 115 referring doctors and 188 referred patients to complete
      questionnaires. We examined the results along with the referral rates to try to
      identify factors that may affect a consultation-liaison psychiatry service.
      Generally, knowledge was poor and attitudes towards psychiatry negative in both
      groups. This negatively influenced the referral rates and reflected the lack of
      integration of psychiatry and medicine at the training level. This is an
      indication that psychiatrists need to work in collaboration with hospital doctors
      to integrate psychiatry into medicine at all levels and emphasizes the priority
      of education of hospital staff, patients and the community in consultation
      liaison psychiatry.

PMID- 17037700
TI  - Differential aspects of consultation-liaison psychiatry in a Saudi hospital. I:
      referral pattern and clinical indices.
AB  - Consultation-liaison psychiatry has emerged as an important sub-specialty in the
      general hospital setting during recent years as a result of psychiatric acute
      wards moving into these hospitals. This has inspired the need for better
      structured research to establish its relevance and effectiveness. We, therefore,
      carried out a prospective cohort study at King Fahad General Hospital. We report
      the interaction of sociodemographic, clinical and diagnostic factors, time lag of
      referral and diagnostic ability of referring physicians. A total of 206 patients
      were referred over a period of 6 months. Sensitivity and specificity of the
      diagnostic skills of the referring doctors were found to be generally poor,
      particularly for anxiety.

PMID- 17037702
TI  - Health Workers for Change: a tool for promoting behaviour change among health
      providers.
AB  - Sensitizing health providers to customers' needs and women's health remains a
      challenge to the Pakistani health system. The Health Workers for Change
      methodology has been demonstrated to improve provider-client relationships in
      certain African and Latin American countries. This paper describes the experience
      of using Health Workers for Change participatory workshops in Pakistan to
      sensitize male and female health providers to gender issues. Health care
      providers identified the unmet needs of women clients as a function of
      individual, household and societal factors, and, unlike the African experience
      with this tool, not predominantly confined to factors associated with the health
      facility.

PMID- 17037703
TI  - Problems related to shiftwork for health care workers at Shiraz University of
      Medical Sciences.
AB  - A cross-sectional study of shiftwork-related problems was carried out among
      health care workers at hospitals of Shiraz University of Medical Sciences,
      Islamic Republic of Iran. Data on personal details, shift schedule and adverse
      effects of shiftwork were collected from 432 randomly selected subjects by
      questionnaire. Sleep, social and subjective problems were more prevalent in
      shiftworkers than day workers. Irregular shiftwork schedules caused more social
      and subjective problems, as well as work dissatisfaction. Voluntary selection of
      shiftworking produced fewer health problems.

PMID- 17037704
TI  - [Current situation of health services in northern districts of the West Bank,
      Palestine].
AB  - We assessed the current situation of health services in the northern districts of
      the West Bank of Palestine as regards the providers of the services, the services
      provided, the human resources working in the services and the sufficiency of the
      services with respect to the size of the populations. We found that 21% of the
      total population in the northern districts did not have private medical clinics
      and 13% did not even have primary health care centres. There has been an increase
      in the number of governmental primary health care centers and a decrease in the
      number of nongovernmental and charitable centres since the Palestinian National
      Authority took over responsibility for public health services through the
      Ministry of Health.

PMID- 17037705
TI  - [Assessment of medical waste management in a Palestinian hospital].
AB  - We studied medical waste management in a Palestinian hospital in the West Bank
      and the role of municipality in this management. In general, "good management
      practices" were inadequate; there was insufficient separation between hazardous
      and non-hazardous wastes, an absence of necessary rules and regulations for the
      collection of wastes from the hospital wards and the on-site transport to a
      temporary storage location inside and outside the hospital and inadequate waste
      treatment and disposal of hospital wastes along with municipal garbage. Moreover,
      training of personnel was lacking and protective equipment and measures for staff
      were not available. No special landfills for hazardous wastes were found within
      the municipality.

PMID- 17037706
TI  - Children's indoor and outdoor play patterns in Ahwaz City: implications for
      injury prevention.
AB  - A cross-sectional study in Ahwaz city, Islamic Republic of Iran, described
      children's indoor and outdoor play patterns. A total of 952 pupils aged 7 and 9
      years and 942 parents completed questionnaires. Children's favourite activities
      were: playing football (22.3%), cycling (13.2%) and watching television (12.3%).
      This differed from those perceived by the parents who reported watching
      television (20.3%), playing football (13.3%) and playing in street (11.4%).
      Children reported their favourite places to play were: street (27.4%),
      park/playground (18.3%) and home (17.8%). There were significant differences in
      play patterns by age and sex. The play patterns of older children and boys
      exposed them to more hazardous situations than younger children and girls.

PMID- 17037707
TI  - Epidemiology of deaths from injuries in the Islamic Republic of Iran.
AB  - A 1-year study of fatal injuries was carried out in 10 provinces of the Islamic
      Republic of Iran based on a population of 16 740 637 in 2000-01. All reported
      deaths were compared and validated with other sources of death registration. Out
      of 66 846 deaths, 9733 (58/100 000) resulted from injuries. Overall, 14.9% of all
      deaths with 26.9% of years of lost life were from injuries. Most fatal injuries
      were unintentional (48.0/100 000). Deaths from traffic injuries (30.0/100 000)
      are the highest in the world. Of 1693 intentional fatal injuries, 61% were due to
      suicide, at a mean age of 29 years.

PMID- 17037708
TI  - Attitudes towards euthanasia among final-year Khartoum University medical
      students.
AB  - To investigate the attitudes of final-year medical students at Khartoum
      University towards euthanasia an anonymous questionnaire was answered by 141
      students. Most were familiar with the concept of euthanasia. The majority, 108
      (76.6%) opposed euthanasia and their reasons included religious beliefs, belief
      that euthanasia was unethical and fear of misuse. The supporters of euthanasia
      (23.4%) stated reasons such as preventing the suffering of patients and
      respecting their autonomy and dignity. More students who described themselves as
      strongly religious were opponents of euthanasia (83/87, 95.4%) than those who
      were moderately religious (25/54, 46.3%).

PMID- 17037709
TI  - [Applying a teaching programme in community-based medical education].
AB  - A community-based medical education programme at Damascus University was applied
      in a local setting from 2 to 12 July 2004 to assess the advantages and
      disadvantages. Three families and 10 medical students participated. The programme
      included teaching objectives, health education and approaches to application and
      evaluation. The design of the programme was appropriate for the community
      setting, but it needed a longer period to run and for contact between the
      students and the community. The students agreed with the structure of the
      programme and the role of the tutor and community, but were concerned about
      difficulties in implementation. Community members were enthusiastic about the
      programme.

PMID- 17037710
TI  - [Smoking among Lebanese mothers: knowledge, attitudes and practices].
AB  - Smoking among women is increasing, especially in women of reproductive age. In a
      cross-sectional study of 1000 Lebanese mothers, we evaluated their knowledge,
      attitude and practice regarding cigarette smoking. We found that the amount of
      tobacco smoked by Lebanese mothers was related to age, educational level,
      profession and knowledge regarding smoking. A woman was more likely to stop or
      decrease smoking during pregnancy if she were more knowledgeable about the
      effects of smoking on the baby, if she smoked less, and if she had a higher
      degree of education. Knowledge about the effects of smoking on the smoker did not
      seem to affect this practice.

PMID- 17037711
TI  - Use of combined oral contraceptives: retrospective study in Isfahan, Islamic
      Republic of Iran.
AB  - We carried out a retrospective cross-sectional study on 500 women in Isfahan who
      started taking combined oral contraceptives (COCs) during the period 21 March
      1995-20 March 1997. The cumulative continuation rate fell from 77% to 12% over 60
      months. The most common reason for discontinuation was side-effects. There was a
      significant correlation between side-effects and cumulative COC continuation rate
      (P < 0.05). The lowest rate was seen in women reporting nausea or vomiting. Women
      who are interested in COCs should receive extensive counselling about the
      possible side-effects and should be helped to find a method of birth control
      suited to their temperament and physiology.

PMID- 17037712
TI  - Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in
      dysmenorrhoea.
AB  - A study in Kerman, Islamic Republic of Iran in 2002 compared the effectiveness of
      fennel and mefenamic acid on pain relief in primary dysmenorrhoea. Two groups of
      high-school girls (mean age 13 years) suffering dysmenorrhoea were randomized to
      receive fennel extract (n = 55) or mefenamic acid (n = 55) for 2 months. In the
      fennel group, 80% of girls and in the mefenamic acid group, 73% of girls showed
      complete pain relief or pain decrease, while 80% in the fennel group and 62% in
      the mefenamic acid group no longer needed to rest. There was no significant
      difference between the 2 groups in the level of pain relief.

PMID- 17037713
TI  - Knowledge, attitudes and beliefs about menarche of adolescent girls in Anand
      district, Gujarat.
AB  - A questionnaire survey of knowledge, attitudes and beliefs towards menstruation
      was made in 22 schools in Anand district, Gujarat state. Of 900 schoolgirls aged
      11-17 years, only 38.5% felt comfortable about menarche and only 31.0% believed
      that menstruation was a normal physiological process. Many (37.2%) had not been
      informed about menarche before its onset and 48.2% felt they were not mentally
      prepared. The major sources of information were the mother (60.7%) or an elder
      sister (15.8%); teachers and others relatives played a small role. In this area
      of India, many families continue the custom of celebrating the first menarche and
      observing social restrictions.

PMID- 17037714
TI  - Prevalence and risk indicators of myopia among schoolchildren in Amman, Jordan.
AB  - We aimed to identify the prevalence and risk factors of myopia among secondary
      school students in Amman. Thus 1777 (1081 males and 696 females) students aged 12
      17 years old were recruited from 8 schools randomly selected from 8 different
      geographic locations in Amman. Data were collected by questionnaire, and self
      reported myopia was checked against school medical records. The prevalence of
      myopia was 17.6%, with no significant difference between males and females after
      adjusting for other possible variables. Myopia was significantly associated with
      age, family history of myopia, computer use, and reading and writing outside
      school. Playing sports was inversely associated with myopia but there was no
      association with watching television.

PMID- 17037715
TI  - Influence of Surgicel gauze on the incidence of dry socket after wisdom tooth
      extraction.
AB  - At a hospital in Damman, Saudi Arabia, it was noticed that many patients had
      developed dry socket after surgical removal of wisdom teeth. To enhance
      haemostasis, Surgicel (oxidized cellulose) gauze was sometimes used in the tooth
      socket in patients who were operated under general anaesthesia. An analysis was
      made of the records of 104 lower wisdom teeth removed surgically from 86
      patients. The incidence of dry socket in the 20 Surgicel-treated teeth was 25.0%,
      compared with 6.0% among the 84 non-Surgicel-treated teeth. The use of Surgicel
      in wisdom tooth extraction seems to be associated with an increased incidence of
      dry socket.

PMID- 17037716
TI  - Wastewater reuse for agriculture: regional health perspective.
AB  - The Eastern Mediterranean Region of the WHO is the poorest region in the world in
      water resources as a Region and per capita. This paper summarizes existing
      practices and constraints regarding wastewater treatment and reuse in the Region
      and describes the health impact of inappropriate practices. Appropriate treatment
      for agricultural use from the health point of view, and the health regulations
      and guidelines for wastewater reuse in the Region are outlined. The work of the
      WHO Regional Office to assist countries face the challenges of water scarcity and
      wastewater reuse are described. Finally, key suggestions that could enhance the
      use of reclaimed wastewater while at the same time safeguarding human health are
      presented.

PMID- 17037717
TI  - Rebuilding of the Lebanese health care system: health sector reforms.
AB  - The civil war in Lebanon from 1975 to 1992 had a significant negative impact on
      the public health care system. This paper describes the health care system in
      Lebanon and its financing as of 2001. The efforts that have been made and are
      being made to rehabilitate and reform this sector since the end of the war are
      outlined.

PMID- 17037718
TI  - Meriones libycus is the main reservoir of zoonotic cutaneous leishmaniasis in
      south Islamic Republic of Iran.
AB  - A study was made in rural regions around Neiriz city, Fars province in the south
      of the Islamic Republic of Iran during 2002-03 to further investigate a new focus
      of zoonotic cutaneous leishmaniasis. Meriones libycus was the dominant rodent
      (100% of 65 rodents collected) and 4.6% were naturally infected with the
      amastigote form of Leishmania spp. Promasigotes were identified as L. major. This
      confirms M. libycus as the main reservoir host of zoonotic cutaneous
      leishmaniasis in southern parts of the country.

PMID- 17037719
TI  - Antiperspirant use as a risk factor for breast cancer in Iraq.
AB  - Some internet communications have addressed the link between antiperspirant use
      and breast cancer. We studied the possible association between the use of
      antiperspirants and some other factors with the development of breast cancer in
      Al-Kadhmia teaching hospital. Thus, 54 cases of breast cancer and 50 controls
      were interviewed. We found 82.0% of the controls used antiperspirants compared
      with 51.8% of cases (P< 0.05). The use of antiperspirants had no association with
      the risk of breast cancer, while family history and oral contraceptives use were
      found to be associated.

PMID- 17037720
TI  - Inguinal hernias and genital abnormalities in young Jordanian males.
AB  - This study was carried out to document the prevalence of inguinal hernia,
      hypospadias, undescended testis and varicocele in 3057 male applicants to the
      military wing of Mu'ta University in the south of Jordan. Age range was 17-20
      years. A total of 250 men had one the 4 conditions: 93 (3.0%) had inguinal
      hernia; 15 (0.5%) had undescended testis (26.7% bilateral); 59 (1.9%) had
      hypospadias; 83 (2.7%) had varicocele (98.79% on the left side). Prevalence of
      inguinal hernia and undescended testis were comparable with international
      prevalence rates, while the rate for hypospadias was higher and that for
      varicocele lower. A birth defects registration system would help in planning
      preventive and treatment strategies.

PMID- 17037721
TI  - Bilharzial infection of a uterine leiomyoma.

PMID- 17037722
TI  - [The cloning and expression of rhlR, a quorum sensing gene in Pseudomonas
      aeruginosa PAO1, and a study of its effect on bacterial clearance rate in mouse
      lung].
AB  - OBJECTIVE: To inquire about the molecular characteristics of rhlR, a Quorum
      Sensing gene in Pseudomonas aeruginosa (P. aeruginosa) PAO1, and to explore the
      immunogenicity of RhlR protein in mouse. METHODS: The rhlR gene of PAO1 was
      amplified by PCR and cloned into pGEX4T-1 plasmid. The recombination was
      expressed in E. coli BL21 (DE3) and analyzed by SDS-PAGE and Western blotting.
      The fusion protein (GST-RhlR) was purified by GST purification Kit and the
      purified protein was used to immunize mice. P. aeruginosa PA0315 was injected
      into mouse lung to explore the immuno-protection of the protein. RESULTS: The 726
      bp DNA fragment of rhlR was amplified from PAO1 general DNA. The restriction
      enzyme map showed that the inserted part of rhlR-pGEX4T-1 was successfully
      constructed and the gene was 100% homologous to rhlR in GenBank. The recombinant
      plasmid expressed a 54 kDa fusion protein (rhlR-GST) in E. coli BL21 (DE3) after
      induction by IPTG. The fusion protein could be recognized by mouse polyvalent
      antiserum against P. aeruginosa. The results showed that the bacterial clearance
      rate in mouse lung was 86. 92% in rhlR groups and 49.44% in the control group.
      CONCLUSION: A 54 kDa protein (RhlR-GST) has been successfully expressed in E.
      coli BL21 (DE3). The RhlR could increase the bacterial clearance rate in mouse
      lung and may serve as immunoprotective antigen to develop the genetic engineering
      vaccine.

PMID- 17037723
TI  - [Quantification for biofilm formation of pseudomonas aeruginosa isolates and
      their genotypic analysis].
AB  - OBJECTIVE: To probe the correlation between the ability of biofilm formation of
      Pseudomonas aeruginosa isolates and their genotypes. METHODS: Forty-eight
      Pseudomonas aeruginosa isolates were tested for their biofilm formation with a
      modified microtiter test and were analyzed by enterobacterial repetitive
      intergenic consensus PCR (ERIC-PCR). The percent similarity between their genetic
      fingerprints and cluster analysis was performed and worked out using computer
      software. RESULTS: Forty-eight Pseudomonas aeruginosa isolates demonstrated
      different abilities of biofilm formation in vitro. And the 48 isolates with
      different abilities of biofilm formation showed different genotypes in
      fingerprints by ERIC-PCR. Among the 48 isolates of Pseudomonas aeruginosa tested,
      five clusters (A, B, C, D, E), were identified at the 17% genetic similarity
      level. The isolates with strong ability of biofilm formation were in D cluster at
      the 42% genetic similarity level. CONCLUSION: Most of the 48 PA isolates tested
      formed strong biofilm, and their genotypes were of correlation.

PMID- 17037724
TI  - [Construction and expression of prokaryotic expression vector pTWIN1/TRAIL].
AB  - OBJECTIVE: To purify an active extracellular region of the TNF related apoptosis
      inducing ligand (TRAIL) protein. METHODS: According to the high-usage codons in
      Escherichia coli and the multiple cloning site of expression vector pTWIN1 of a
      self-splicing prokaryotic expression system, the extracellular region of TRAIL
      gene was designed and synthesized, which was cloned into pMD18-T vector. After
      pMD18-T/TRAIL and pTWIN1 were digested by Nru I and EcoR I, the target fragment
      purified was linked to the expression vector pTWIN1, which was transferred into
      the competent cell JM109, and positive recombination was screened. After positive
      recombination vector pTWIN1/TRAIL (identified with restrictive endonuclease
      digesting and sequencing) was transferred into the ER2566, the expression was
      induced by different IPTG concentration at different temperature and culture
      time. The expression products were analyzed by 150 g/L SDS-PAGE. RESULTS: The
      extracellular region of TRAIL gene was obtained by PCR, and was constructed
      successfully in a self-splicing prokaryotic expression vector pTWIN1/TRAIL. By
      0.3 mmol/L IPTG at 15 degrees C for 14 to 16 hours, the soluble target protein
      was expressed efficiently. CONCLUSION: High-expression level of the extracellular
      region of TRAIL fusion protein was attained by use of E. coli ER2566, and the
      soluble target protein without any additional amino acid was successfully
      purified by simple treatment.

PMID- 17037725
TI  - [The cloned ctxA gene of vibrio cholerae expresses in E. coli].
AB  - OBJECTIVE: To construct the expression vector of Vibrio cholerae ctxA gene, and
      realize the Vibrio cholerae ctxA gene to express in E. coli, and lay a basis for
      future research on the immunogenicity and immunoadjuvant. METHODS: The ctxA gene,
      an cholera toxin subunit gene (ctxA) of Vibrio cholerae, was obtained by
      polymerase chain reaction (PCR) from DNA of Vibrio cholerae, and cloned into
      prokaryotic expressed vector pET32a(+) with thioredoxin (Trx) gene. The
      recombinant plasmid (pET-ctxA) was analyzed to identify with restriction
      endonuclease digestion, PCR and DNA sequencing analysis. And then the pET-ctxA
      was transferred into E. coli strain BL21 (DE3) for transformation. The ctxA
      expression of pET-ctxA was induced with isopropy-beta-D-thiogalactoside (IPTG)
      and the fused protein Trx-CTA was examined by SDS-PAGE and Western blot
      techniques. RESULTS: Restriction endonuclease digestion, PCR and DNA sequencing
      analyses showed that the ctxA gene of 787 bp was amplified from Vibrio cholerae
      DNA, and the recombinant plasmid pET-ctxA was successfully constructed, and the
      ctxA expression in prokaryotic cell was detected by SDS-PAGE and Western blot
      techniques. CONCLUSION: The ctxA gene of Vibrio cholerae, in fused protein form
      with Trx, got a high expression in E. coli.

PMID- 17037726
TI  - [The influence with block the endotoxin signal transduction for
      ischemia/reperfusion injury of graft liver in rats].
AB  - OBJECTIVE: To explore the feasibility of interleukin 1 receptor associated kinase
      4 (IRAK-4) as gene therapy target for liver ischemia/reperfusion injury (I/RI)
      and effective approach in vivo for short hairpin RNA (shRNA) interference used to
      gene therapy in liver graft hqappened. METHODS: Sprague-Dawley rats were randomly
      divided into three groups: the control group, the in vivo transfection group
      (IVT) and the cold ischemia transfection group (CIT). Experiments of orthotopic
      liver transplantation were performed by two-cuff method. CIT were perfused with
      IRAK-4-shRNA plasmid (pSIIRAK-4) during cold ischemia phase, IVT received the
      equivalent volumes (2 mL) of pSIIRAK-4 after portal vein inosculated, and the
      control group leaved without any treatment. At 0 min, 60 min and 180 min after
      reperfusion, the expression of IRAK-4 gene and protein level were determined by
      RT-PCR and Western blot. The serum TNF-alpha level was detected by ELISA. Liver
      histopathological changes and cell apoptosis were observed by electron microscope
      and TUNEL. RESULTS: After reperfusion, the expression of IRAK-4 were largely
      depressed in CIT than that of IVT and the control group (P < 0.01), and
      furthermore, the serum TNF-alpha level, proportion of hepatocyte apoptosis and
      severity of hepatocyte injury were also lower than the latter. CONCLUSION: These
      results indicate that depression IRAK-4 expression with IRAK-4-shRNA through
      portal vein perfusion during cold ischemia phase could effectively blunt graft
      hepatic I/RI.

PMID- 17037727
TI  - [Evidence for the presence of motilin receptor and a study on the mechanism of
      motilin induced Ca2+ signaling in rat myenteric neurons].
AB  - OBJECTIVE: To observe whether the motilin receptor (MTLR) can be expressed in
      primarily cultured myenteric neurons of rats and investigate the mechanism of
      motilin induced Ca2+ signaling in myenteric neurons of rats. METHODS: Expression
      of the motilin receptor was identified with double-immunofluorescence staining
      technique. Data on the intracellular Ca2+ concentration ([Ca2+]i) of cultured
      myenteric neurons with different treatments were collected by measuring Ca2+
      fluorescent intensity (FI) in each neuron under confocal microscope. RESULTS: The
      cultured myenteric neurons showed positive motilin receptor immunoreactivity. In
      Hank's solution, 10(-6) mol/L motilin could elevate [Ca2+]i, its height of peak
      being 30.6 +/- 3.7 and its FI relative change percentage being (100. 8 +/-
      18.4)%. In D-Hank's solution (after removal of extracellular Ca2+, or after
      treatment with verapamil,an L-type calcium channel blocker), motilin could induce
      a small increase of [Ca2+]i. After pretreatment with NEM,a G protein inhibitor,
      and Compound 48/80, a PLC inhibitor, in Hank's solution respectively, motilin was
      inhibited and the [Ca2+]i was significantly lower than that of the group to which
      was added only motilin (P < 0.05). After pretreatment with D-sphingosine, a PKC
      inhibitor, the effect of motilin was not significantly different from that of the
      group to which was added only motilin (P > 0.05). CONCLUSION: The motilin
      receptor could be expressed by cultured myenteric neurons of rats. Motilin could
      increase [Ca+]i. The increase of [Ca2+]i was caused by release of intracellular
      stores and influx of extracellular Ca2+, mainly through the L-type calcium
      channel. The motilin receptor-coupled G-protein, PLC and IP3 pathway participated
      in the release of Ca2+ from intracellular stores.

PMID- 17037728
TI  - [Effect of batroxobin on K+ channel activated by Ca2+ in primary culture rat
      cortex neurons of rat].
AB  - OBJECTIVE: To investigate the effect of batroxobin on K+ channel activated by
      Ca2+ in primary cultured cortex neurons of fetal SD rat. METHODS: The patch clamp
      technique of single channel recordings including cell-attach and inside-out mode
      was used. RESULTS: Extracellular batroxobin activated the Kca. In Ca2+ bath
      solution of cell-attach mode, Vp +30 mV, when the concentrations of batroxobin
      were 0.15, 0.25, 0.50, 0.75 and 1.0 mmol/L, the open probabilities of the channel
      were 0.013 +/- 0.002, 0.082 +/- 0.011, 0.131+/- 0.012, 0.211+/- 0.010 and 0.062
      +/- 0.009 (P < 0.01), respectively. It appeared concentration-dependent within
      0.75 mmol/ L. batroxobin. In Ca2+ free-bath solution of cell-attach mode, Vp+50
      mV, when the concentrations of batroxobin were 0.15, 0.40, 0.60 and 1.0 mmol/L,
      the open probabilities of the channel were 0.013 +/- 0.001, 0.112 +/- 0.007,
      0.193 +/- 0.010 and 0.301 +/- 0.009 (P < 0.05), respectively. In the 6 cases of
      inside-out mode patch clamp, Vp +40 mV, when the concentrations of batroxobin
      were 0, 0.25 and 0.50 mmol/L, the open probabilities of the channel were 0. 012
      +/- 0.007, 0.011 +/- 0.009 and 0.013 +/- 0.008 (P > 0.05), respectively. There
      was no significant difference in open probabilities, average open/close times and
      amplitudes at different intracellular batroxobin concentrations. CONCLUSION:
      Batroxobin can affect the activation of the Kca channel through regulating the
      concentration of cytoplasmic free Ca2+. It may have a protective effect on
      neurons.

PMID- 17037729
TI  - [Changes of mitochondrial membrane potential (delta psi m) and calcium
      concentration in cultured glomerular mesangial cells of rats with obstructive
      jaundice].
AB  - OBJECTIVE: To explore the effect of mitochondrial membrane potential (delta psi
      m) and calcium concentration on the kidney injury of rats with obstructive
      jaundice and to probe into the underlying mechanism. METHODS: Sixty male Sprague
      Dowley rats, weighing 200 g to 250 g were randomly divided into three groups:
      control group; sham operation group; experiment group. And the rats of experiment
      group were subdivided into two groups according to the time (15 d, 21 d) after
      the common bile duct ligation. The experiment groups were rendered jaundiced by
      doubly ligating the common bile duct. Glomeruli were isolated, the glomerular
      mesangial cells (GMCs) were cultured. The mitochondrial membrane potential (delta
      psi m) was measured by flow cytometry; the concentration of calcium was measured
      by confocal microscopes. RESULTS: The amount of mitochondrial membrane potential
      (delta psi m) was decreased (P < 0.05) in the rats with obstructive jaundice,
      compared with the control; the concentration of calcium was increased (P < 0.05)
      in the rats with obstructive jaundice, compared with the control. Conclusion The
      calcium incurrent that leads to changes in amount of mitochondrial membrane
      potential (delta psi m) has significant effect on the kidney injury of the rats
      with obstructive jaundice.

PMID- 17037730
TI  - [Human amnion cells express the phenotypes of neural cells and adipocytes in
      vitro].
AB  - OBJECTIVE: To search for culture conditions in which the cells from human amnion
      could diferentiate into neural cells and hence to explore a new cell source for
      neural transplantaion. METHODS: Amnion cells from human were cultured with tissue
      piece method, passaged by trypsin digestion and identified with
      immunocytochemistry. RESULTS: Amnion cells migrated from explants and primary
      culture was established; they could multiply and expand steadily in a short time,
      and they could be passaged by trypsin digestion. When cultured in serum-free
      neural stem cell media, these cells could form the same spheroid shape as the
      neurospheres of neural stem cells. They could express alpha smooth muscle actin
      and differentiate into smooth muscle cells spontaneously, and could express
      nestin and vimentin, the markers for neural progenitors. Moreover, they could he
      stained by anti-beta III-tubulin, anti-neurofilament 200 and anti-NSE; the
      majorities could he stained by antityrosine hydroxylase, the marker for
      dopaminergic neurons. Lower than 0.1% of the total cells were stained by GFAP,
      indicating the existence of astrocytes. The amnion cells could also differentiate
      into adipocytes under specific induction. CONCLUSION: Amnion cells could
      differentiate into adipocytes and smooth muscle cells; they could express the
      protein for neural cells; thus may represent an alternative stem cell source for
      CNS cell transplantation.

PMID- 17037731
TI  - [A study on transfection of green fluorescence protein gene into human adipose
      stromal cells in vitro].
AB  - OBJECTIVE: To make a comparison on the efficiency of two methods for transfecting
      Green Fluorescence Protein gene into human adipose tissue-derived stromal cells,
      and to study the biological properties and multipotential differentiation of gene
      transfected cells. METHODS: The human subcutaneous adipose tissue was obtained,
      digested with one volume of collagenase type I, and then cultured with BGJb
      medium. After subculture and expansion, the human adipose tissue-derived stromal
      cells infected with Ad-GFP or liposome were observed and analyzed with
      fluorescence microscopy and flow cytometry to assess transfection efficiency. The
      growth curve of transfected adipose tissue-derived stromal cells was protracted.
      The adipose tissue-derived storomal cells were induced to differentiate into
      osteoblasts, and non-transfected cells were set as control. RESULTS: 42.5% +/-
      1.5 of the human adipose tissue-derived stomal cells infected with Ad-GFP were
      found to express GFP at a level higher than that of the control of liposome
      (11.40%). Infected adipose tissue-derived stromal cells were noted to form
      mineralized nodes by the use of Alizarin Red stain. CONCLUSION: The human adipose
      tissue-derived stromal cells infected with Ad-GFP can express higher level of
      GFP, and can maintain the ability of proliferation and differentiation as the non
      infected human adipose tissue-derived stromal cells do. The infected adipose
      tissue-derived stromal cells with Ad-GFP can track the change of adipose tissue
      derived stromal cells in the study of multipotential differentiation and can
      serve as cellular vehicles for systemic gene delivery.

PMID- 17037732
TI  - [Anti-tumor effects of recombinant adenovirus encoding survivin encapsulated in
      cationic liposome].
AB  - OBJECTIVE: To explore the anti-tumor effects and mechanisms of recombinant
      adenovirus encoding survivin encapsulated in cationic liposome. METHODS: CT26
      tumor model was established in BALB/c mice. Fifty mice were randomly divided into
      five groups, including the group treated with recombinant adenovirus encoding
      survivin encapsulated in cationic liposome (Lip+ Ad-sur), the group of
      recombinant adenovirus encoding survivin (Ad-sur), the group of recombinant
      adenovirus encoding null encapsulated in cationic liposome (Lip+Ad-null), the
      group of liposome (Lip), and the group of PBS alone (PBS). Survival rate of mice,
      tumor volume, and side effects of treatments were observed. Lymphocytes were
      activated by adenovirus vaccine to kill tumor cells in vitro and in vivo. CTL
      assay and histological examination were carried out. RESULTS: Immunotherapy with
      recombinant adenovirus encoding survivin encapsulated in cationic liposome was
      effective for inducing protective and therapeutic anti-tumor immunity in CT26
      tumor model. In the combination therapy group, the tumor growth was inhibited and
      the tumor volume was significantly smaller when compared with the controls. The
      survival rate of mice in the combination therapy group at 7 weeks after
      inoculation of tumor cells was significantly higher than that of the control
      group. Histologically, the tumor tissue was markedly necrotic and was infiltrated
      by lymphocytes. 51Cr assay in vitro indicated that the combination therapy group
      showed higher specific killing activity against CT26 tumor cells than did the
      control groups, and the T cells were independent of NK cells. CONCLUSION:
      Immunotherapy with recombinant adenovirus encoding survivin encapsulated in
      cationic liposome was noted to have a significant anti-tumor effect on CT26 tumor
      model.

PMID- 17037733
TI  - [An experimental research on the combination treatment of sFLK-1 gene therapy
      combined with gamma knife].
AB  - OBJECTIVE: To evaluate whether the sustained expression by adenovirus-mediated
      gene (sFLK-1) transfer can enhance the treatment efficacy of gamma knife
      radiosurgery. METHODS: The mouse sFLK-1 gene was cloned to construct the
      recombinant adenovirus. The gliomata growing in BALB/c female nude mice with an
      initial mean volume of (109.3 +/- 20.5) mm3 were treated with gamma knife alone
      (13 Gy on day 12), sFLK-1 adenovirus alone (1 x 10(9) plaque-forming units, PFU
      was given to two mouse tail vein by injections, 7 and 14 days), gamma knife
      associated with sFLK-1 adenovirus or control adenovirus (1 x 10(9) PFU was given
      to two mouse tail vein by injections, 13 and 17 days). After the completion of
      therapy, the tumor size was recorded. The microvessel density (MVD) and tumor
      apoptosis were evaluated by immunohistochemical means. RESULTS: As comparing with
      three other control groups, the combination treatment group with sFLK-1 gene
      therapy and gamma knife not only significantly reduced tumor volume and prolonged
      the life span of tumor burden mice as well. In addition, the average tumor
      weights were lower in sFLK-1 combined with gamma knife group than in any other
      control group. Immunohistochemical analysis of glioma demonstrated a decreased
      MVD and a high apoptosis cell rate in sFLK-1 combined with gamma knif group.
      CONCLUSION: The antitumor effect of gamma knife can be potentiated by sFLK-1 gene
      therapy. Thus the combination of sFLK-1 gene therapy and gamma knife results an
      additive effect of antitumor. The observation may provide an important strategy
      for treatment cancer metastasis.

PMID- 17037734
TI  - [Effect of lenti-mCCL20 on the growth of mouse tumor].
AB  - OBJECTS: We aim at inducing a potent antitumor immune response via CCL20
      expressing in situ tumor. METHODS: We constructed a recombinant lentivirus
      encoding mouse CCL20 cDNA and transduced the mouse mesenchymal stem cells (mMSCs)
      in vitro, and then selected the transfected cells to get a stable mixed mCCL20
      expressing pool (named as lenti-mCCL20-mMSCs) with blasticidin. By the same
      means, we produced another pool named as lenti-null-mMSCs. The CT26 was mixed
      with lenti-mCCL20-mMSC and inoculated sc into the left hinder back of BALB/c
      mouse. And also the CT26 was alone, or mixed with lenti-null-mMSCs or parent
      mMSCs, and then inoculated sc into BALB/c mice serving as controls. RESULTS: We
      got a lenti-mCCL20-mMSCs expression construct. It was shown that mCCL20 increased
      intratumoral lymphocytes infiltration and facilitated tumor growth in syngeneic
      murine tumor model. CONCLUSIONS: CCL20 expressing in situ tumor enhances
      intratumoral lymphocytes infiltration but facilitates tumor growth. However, the
      mechanism involved remains to be further elucidated.

PMID- 17037735
TI  - [Effects of soy isoflavone on gene expression of resistin in insulin-resistance
      rats].
AB  - OBJECTIVE: To assess the effects of soy isoflavone (SIF) on improving insulin
      reistance (IR) status in IR rats induced by high-fat and high-sugar diet and
      explore the possible mechanisms. METHODS: IR rats were randomly divided into four
      groups according to their insulin resistance indices (IRI). The rats in one model
      control group and three SIF groups were fed via gavage with water solutions
      containing SIF at doses of 0 mg/ kg x bw, 50 mg/kg x bw, 150 mg/kg x bw, and 450
      mg/kg x bw, respectively. After one month, fasting glucose, fasting insulin,
      resistin in serum, and resistin mRNA in adipocyte around kidney were detected by
      enzymologic method, radioimmunoassay, enzyme linked immunosorbent assay, and real
      time RT-PCR, respectively. RESULTS: Comparison between the model control group
      and the other groups revealed that serum resistin and resistin mRNA expression
      levels were lower in the 450 mg/kg x bw group, that insulin and IRI levels were
      lower in the 150 mg/ kg x bw group and 450 mg/kg x bw group, and that no
      differences in plasma glucose levels existed among the 4 groups. A positive
      correlation between IRI and serum resistin level (r = 0.355, P < 0.05) was
      observed. CONCLUSION: These results suggest that soy isoflavone may down-regulate
      resistin mRNA expression, decrease serum resistin level and enhance insulin
      sensitivity.

PMID- 17037736
TI  - [Effects of TGF-beta1, gene modified donor dendritic cells on immune repulsion].
AB  - OBJECTIVE: To examine the inhibitory action of the injection of TGF-beta1 gene
      modified donor dendritic cells (TGF-beta1-DC) on the immune repulsion in rat
      liver transplantation and detect the related mechanism. METHODS: The recombinant
      TGF-beta1-pcDNA3 adenovirus transfected Wistar DCs were injected into the tail
      vein of the recipient SD rat. One week later, the rat immune repulsion model of
      liver transplantation was set up, the expression of TGF-beta1 gene was
      identified, and the survival was observed and recorded. The NF-kappaB activity
      and cell factor TNF of T cells in recipient spleen and Kupffer cells were
      detected by electrophoretic mobility shift assay and immunohistochemistry
      respectively. The pathological rejection index after transplantation was assayed.
      RESULTS: The rejection index was decreased and the survival time was prolonged in
      Ad-TGF-beta1-DC group as compared with those in control groups. Also it was found
      that TGF-beta1-DC injection inhibited the expression of NF-kappaB and TNF of T
      cells and Kupffer cells in rat liver allografts, and all differences were
      statistically significant. CONCLUSION: TGF-beta1 gene modified DC could obviously
      inhibit the activation of T cells and Kupffer cells, enhance the tolerogenicity
      of liver transplantation and prolong survival time.

PMID- 17037737
TI  - [Effect of ligustrazine on cell proliferation in subventricular zone of lateral
      cerebral ventricle after adult rat suffering from focal cerebral ischemia].
AB  - OBJECTIVE: To explore the effect of ligustrazine on cell proliferation in
      subventricular zone of lateral cerebral ventricle after middle cerebral artery
      occluded (MACO) in adult rat. METHODS: SD male rats were randomly divided into
      three group: sham operation group, ischemic model group and Ligustrazine group.
      The model of the middle cerebral artery occlusion was established by placement of
      an intraluminal filament at the origin of left MCA. Ligustrazine was administered
      intraperitoneally with a dose of 80 mg/kg daily starting at 2 hours after MCAO.
      BrdU (50 mg/kg) was injected once a day intraperitoneally starting at 4 hours
      after operation. Number of BrdU-positive cells and expression of doublecortin
      (DCX) in subventricular zone (SVZ) were measured by immunohistochemistry on day
      7, 14, 24 after operation. RESULTS: Compared with sham operation group, BrdU
      positive cells in ischemic model group increased on day 7, reached the peak on
      day 14, then decreased on day 21 after operation. On day 7 and 14, the numbers of
      BrdU-positive cells in Ligustrazine group were markedly augmented and
      significantly more than those in ischemic model group (P < 0.01), but decreased
      on day 21. The expressions of DCX in SVZ in ischemic model group were enhanced on
      day 7 with lasting into day 14, and reduced on day 21, but still higher than
      those in sham operation group on day 7, 14, and 21, respectively. The expressions
      of DCX in SVZ in Ligustrazine group increased gradually along with prolong of
      ischemia and kept the high level up to day 21 after operation, and were higher
      than those in ischemic model group on day 14 and 21. CONCLUSION: Our results
      suggest that Ligustrazine may promote the cells of SVZ, which the adult rats
      suffer from the focal cerebral ischemia, to go into cell proliferation.

PMID- 17037738
TI  - [A study on expression of HIF-1alpha and EPO in the hippocampus of rats with
      vascular dementia].
AB  - OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF
      1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and
      investigate the possible pathogenesis of VD. METHODS: Rats of experimental group
      were treated with a permanent bilateral common carotid arteries (CCA) occlusion
      (2-VO) for establishing vascular dementia model. Rats were evaluated on learning
      memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha
      and EPO in hippocampal CA1 region were measured by immunohistochemical assay
      method. RESULTS: (1) The learning-memory ability of rats in VD groups was
      progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD
      group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most
      obvious at 1 w, and then declined progressively but still above the normal level
      (P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each
      ischemic point and their corresponding learning-memory ability were in
      significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO
      contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may
      play a protecting role in this process.

PMID- 17037739
TI  - [Inhibitory effects of deoxyribozyme on the expression of Period1 gene in vitro
      and on morphine-induced psychic dependence in mice].
AB  - OBJECTIVE: To investigate the regulatory effects of deoxyribozyme on the
      expression of Period 1 gene in vitro and on the morphine-induced psychic
      dependence in mice. METHODS: The specific deoxyribozymes toward Period 1 mRNA was
      designed by MFold analysis and synethsized chemically. By LipofectAMINE mediated
      DNA transfection technique, DRz164 and pcDNA3-Per1 were introduced into NIH3T3
      cells. The effects of deoxyribozyme on Period 1 gene were studied by reverse
      transcript-polymerase chain reaction (RT-PCR) and flow cytometry(FCM). The
      morphine-induced reward in mice was observed in a conditioned place preference
      test after pretreatment of the mice with the intracerebroventricular
      administration of deoxyribozyme. RESULTS: After NIH3T3 cells were transfected by
      pcDNA3-Per1 and DRz164, the Period 1 mRNA was reduced by 42.4%. And PERIOD
      proteins were decreased by 57.5%. After being pretreated with deoxyribozyme, the
      mice did not show morphine-induced place preference. CONCLUSION: DRz164 can
      highly block the expression of Period 1 gene, which cleaves the Period 1 mRNA in
      the transfected cells specifically. The suppression of morphine-induced place
      preference can be effected by pretreating the mice with alleviating their psychic
      dependence on morphine.

PMID- 17037740
TI  - [Expression level of cubilin in the rat model of diabetic nephropathy].
AB  - OBJECTIVE: To observe the expression level of Cubilin in the renal tubules of
      rats with STZ-induced diabetic nephropathy, to assess its correlation with 24
      hours' albuminuria, and to investigate the mechanisms of tubular dysfunction at
      the early stage of diabetic nephropathy. METHODS: Diabetic nephropathy was
      induced in Sprague-Dalwley rats by intraperitoneal injection of STZ, while the
      rats of normal group were injected with normal saline. Biochemical indices of
      blood and urine specimens were observed in both groups at weeks 2, 4 and 6
      respectively. The renal expression levels of Cubilin in the two groups were
      determined by immunohistochemistry and RT-PCR. RESULTS: The expression level of
      Cubilin in the diabetic nephropathy group was significantly decreased at week 2
      after operation (P < 0.05), and it continued to decrease from week 2 to week 6.
      Also there was significant difference between each two time-points (P < 0.05),
      and the Cubilin expression level was negatively correlated with albuminuria (P <
      0.01). CONCLUSION: The decreased expression level of Cubilin in early-stage
      diabetic nephropathy rats may partly contribute to the development of
      microalbuminuria. Cubilin can be regarded as one of the early markers when
      tubular dysfunction develops in the case of diabetic nephropathy.

PMID- 17037741
TI  - [Differential regulation of P2X3 mRNA expression in the rat trigeminal ganglion
      after experimental tooth movement].
AB  - OBJECTIVE: To investigate the regulation of P2X3 mRNA expression in the
      trigeminal ganglion sensory neurons after the nociceptive stimulation by
      orthodontic tooth movement force. METHODS: Male Sprague-Dawley rats weighing 200
      250 g were used. The mimic tooth movement appliance was used in the rats of the
      experiment group. The rats were sacrificed after 4 h, 12 h, 1 d, 2 d, 3 d, 5 d
      and 7 d after experiment. The expression of P2X3 mRNA was detected by in situ
      hybridization with an oligonucleotide probe. RESULTS: After force was given to
      the teeth of rats, the number of P2X3 mRNA positive neurons increased on the
      first day and reached the peak on the third day; then, the level of P2X3 mRNA
      expression began to decrease, and after seven days, it returned to the level of
      the control group. CONCLUSION: The results suggest that the P2X3 mRNA expression
      is transiently upregulated and anterogradely transported in trigeminal primary
      sensory neurons after orthodontic tooth movement and that P2X3 receptor may play
      a role in the pathomechanism of nociception in primary sensory neurons during
      orthodontic treatment.

PMID- 17037742
TI  - [Expression of PPAR-gamma in human hilar bile duct carcinoma cell line QBC939 and
      the effects of PPAR-Y activated by its ligand on the growth of QBC939].
AB  - OBJECTIVE: To explore the expression of Peroxisome Proliferator-activated
      Receptor-gamma (PPAR-gamma) in QBC939 and the effects of PPAR-gamma activated by
      its ligand pioglitazone on the growth of human bile duct carcinoma cell line.
      METHODS: QBC939 cells were cultured and treated with different concentration of
      pioglitazone; the expression of PPAR-gamma mRNA was detected by RT-PCR; the
      effects of PPAR-gamma activated by its ligand on cell proliferation were examined
      by cell count under light microscope; the influences of activated PPAR-gamma on
      cell cycle were examined by flow cytometry, and the apoptosis of cancer cells
      induced by PPAR-gamma ligand pioglitazone was detected by flow cytometry and
      TUNEL methods. RESULTS: PPAR-gamma was expressed in human hilar bile duct
      carcinoma cell line QBC939. And after PPAR-gamma was activated by its ligand
      pioglitazone, it significantly inhibited cell proliferation, produced G2/M phase
      arrest and induced apoptosis of QBC939. CONCLUSIONS: PPAR-gamma, after being
      activated by its ligand pioglitazone, can inhibit the cell growth of QBC939
      remarkably through suppression of cell proliferation, increase in proportion of
      G2/M phase cells and induction of apoptosis, so PPAR-gamma may be a molecular
      therapeutical target against the human bile duct carcinoma.

PMID- 17037743
TI  - [Reflux of bile induces esophageal mucosal inflammation and apoptosis in rats].
AB  - OBJECTIVE: To investigate the esophageal mucosal inflammation and apoptosis
      induced by reflux of different duodenal or bile in rats. METHODS: Esophagus
      division in esophagogastric junction and then esophagoduodenostomy were performed
      on rats to make the models of duodenogastroesophageal reflux (DGER). Three kinds
      of reflux model, DGER (Group A), duodenoesophageal reflux without gastric juice
      (Group B) and DGER without bile (Group C) were made by adjusting the DGER models.
      9 weeks after operation, the esophageal mucosal inflammation was examined under
      microscope, and the esophageal apoptosis was tested by DNA fragmentation in situ
      using TdT-mediated dUTP biotin nick end labling (TUNEL). Immunohistochemical
      method was used to detect the status of esophageal Fas protein (CD95) associated
      apoptosis. RESULTS: Evidences of reflux esophagitis were seen in all rats with
      different reflux models. Esophageal inflammation was most severe in group A, then
      in group B, and the slightest in group C. Barrett's esophagus was seen in group A
      and group B but not in group C, and the incidence was found to be of no
      difference between the A and B groups (P > 0.05). Esophageal mucosal apoptosis
      index in group A was (7.05 +/- 1.44)%, being significantly higher than that in
      group B (5.25 +/- 1.78)% and group C (2.84 +/- 1.36)%, (P < 0.01). The apoptosis
      index was significantly higher in group B than in group C (P < 0.01). Fas protein
      was negative in normal tissues and in all injured esophageal mucosal tissues.
      CONCLUSION: The DGER without bile inflicts the slighest injury on the esophageal
      mucosa. Bile may play a significant role in the induction of Barrett's esophagus.
      The apoptosis indices increase in groups A, B and C, but apoptosis is not
      correlated with Fas expression.

PMID- 17037744
TI  - [Expression level and significance of TGF-beta1, PDGF, CTGF in serum of patients
      with pneumoconiosis].
AB  - OBJECTIVE: To explore the TGF-beta1, PDGF, CTGF serum expression significance in
      the occurrence and development of pneumoconiosis. METHODS: The serum levels of
      TGF-beta1, PDGF, CTGF in 70 patients with pneumoconiosis (including 29 patients
      with silicosis and 41 patients with coal pneumoconiosis) and 77 healthy
      individuals were detected by means of enzyme linked immunosorbent assay (ELISA).
      RESULTS: The serum levels of TGF-beta1, PDGF, CTGF in patients with
      pneumoconiosis were (44.95 +/- 23.72) ng/mL, (56.95 +/- 55.68) ng/mL, (346.70 +/-
      259.49) pg/mL, the serum levels of control group were (6.81 +/- 4.99) ng/mL,
      (30.96 +/- 21.63) ng/mL, (307.49 +/- 235.40) pg/mL. There were significantly
      statistical differences between the case group and the control group in the serum
      levels of TGF-beta1 and PDGF (P < 0.05). There was no significantly statistical
      difference between the two groups in the serum levels of CTGF (P > 0.05). The
      serum levels of TGF-beta1 and PDGF in the patients with silicosis were higher
      than those in the patients with coal pneumoconiosis, and there was significantly
      statistical difference between the two groups (P < 0.05). The serum levels of TGF
      beta1 and PDGF in the patients with pneumoconiosis decreased with the
      pneumoconiosis stage going up (P < 0.05). There was the bivariate correlation not
      only between the serum levels of TGF-beta1 and PDGF in the whole objects but also
      the serum levels of CTGF and PDGF (P < 0.05). CONCLUSIONS: The serum levels of
      TGF-beta1, PDGF, CTGF in the patients with pneumoconiosis may correlate with the
      pathological stages, styles and degree of pneumoconiosis.

PMID- 17037745
TI  - [Effects of nonsteroidal anti-inflammatory drug celecoxib on expression of
      cyclooxygenase-2 (COX-2) in ovarian carcinoma cell].
AB  - OBJECTIVE: To explore the effects of nonsteroidal anti-inflammatory drug
      Celecoxib on the expression of cyclooxygenase-2 (COX-2) in the SKOV3 cell line
      and the xenografted nude mice of ovarian carcinoma. METHODS: The expression of
      COX-2 in the SKOV3 cell was determined by reverse transcription polymerase chain
      reaction (RT-PCR), flow cytometry (FCM), and Western blot analysis. The
      expression of COX-2 in tumor cells was measured with Immunocytochemistry.
      RESULTS: RT-PCR showed that the expression COX-2 mRNA was strongly down-regulated
      in SKOV3 cells after treatment with Celecoxib or Aspirin. FCM and Western blot
      analysis showed that the protein product of COX-2 was strongly decreased by
      Celecoxib or Aspirin. The Celecoxib was more potential effects than Aspirin. The
      immunocytochemistry result showed that the expression of COX-2 in 10, 25, 50
      mg/kg x d of Celecoxib were lower obviously than it in the control group in
      Xenografted nude mice. CONCLUSION: The anticarcinogenic effects of Celecoxib is
      probably related to the down-regulation of COX-2, and can be explained to both
      COX-2-dependent and -independent mechanisms.

PMID- 17037747
TI  - [The relativity of vascular endothelium growth factor receptor-1 and
      preeclampsia].
AB  - OBJECTIVES: (1) To investigate the levels of the serum soluble endothelial growth
      factor receptor-1 in women with preeclampsia and compare the difference between
      the groups of the mild preeclampsia, severe preeclampsia and eclampsia. For more,
      to analyze the relativity between the levels of the serum soluble vascular growth
      factor receptor-1 and preeclampsia. (2) To detect the expression of the membrane
      bound VEGFR-1 protein in the placenta tissue of the women with preeclampsia and
      compare the difference between the groups of the mild preeclampsia, severe
      preeclampsia and eclampsia, Then to analyze the relativity between the expression
      of the membrane-bound endothelial growth factor receptor-1 and preeclampsia.
      METHODS: (1) The serum levels of sVEGFR-1 in 10 women with mild preeclampsia, 10
      women with severe preeclampsia, 10 women with eclampsia, 10 women without
      preeclampsia were detected by the quantitative sandwich enzyme immunoassay
      technique. (2) Immunohistochemistry and quantitative analysis were used to detect
      membrane-bound VEGFR-1 contents and distribution in the placenta tissue. RESULTS:
      (1) The results showed that the serum sVEGFR-1 levels of all preeclampsia groups
      were relatively higher than those of control group (P < 0.05) and that there were
      significant differences between the groups of the mild preeclampsia, severe
      preeclampsia and eclampsia. (2) In placentas, the positive staining was detected
      predominantly in the membranes of villus syncytiotrophoblast cells, extravillous
      trophoblast cells, and villus endothelial cells. In fetal membranes, the positive
      staining was detected predominantly in amnionic endothelial cells. (3) The
      contents of membrane-bound VEGFR-1 in placenta of preeclampsia groups were
      relatively lower than that of control group. There were significant differences
      between membrane-bound VEGFR-1 contents of the mild preeclampsia,severe
      preeclampsia and eclampsia (P < 0.05). (4) The ratio of the sVEGFR-1
      concentration in serum and the membrane-bound VEGFR-1 contents in placenta of
      preeclampsia groups (sVEGFR-1/ membrane-bound VEGFR-1) was relatively higher than
      that of control group (P < 0.05) and there were significant differences between
      the groups of the mild preeclampsia, severe preeclampsia and eclampsia (P <
      0.05). CONCLUSIONS: (1) The serum sVEGFR-1 levels of preeclampsia groups were
      relatively higher than those of control group, the VEGFR-1 may be related to
      preeclampsia. (2) The contents of membrane-bound VEGFR-1 in placenta of
      preeclampsia groups were relatively lower than that of control group, the
      membrane-bound VEGFR-1 may relate to preeclampsia. (3) The ratio of the sVEGFR-1
      concentration in serum and the membrane-bound VEGFR-1 contents in placenta of
      preeclampsia groups (sVEGFR-1/membrane-bound VEGFR-1) was relatively higher than
      that of control group, the preeclampsia may contribute to VEGFR-1/ PLGF and
      sVEGFR-1/membrane-bound.

PMID- 17037746
TI  - [TRAIL impacts in growth and apoptosis of human ovarian carcinoma cell line
      SKOV3].
AB  - OBJECTIVE: To investigate the effect of TRAIL on growth and apoptosis of ovarian
      carcinoma cell line SKOV3. METHODS: The effects of TRAIL alone and/or associating
      with DDP to treat on SKOV3 cells growth inhibition were measured by MTT assay,
      and the changes of DR4 and DR5 mRNA were detected by RT-PCR technique. The cell
      cycle and apoptosis index were analyzed by technique of Flow Cytometry (FCM).
      RESULTS: The soluble TRAIL protein had the inhibiting effect on the growth SKOV3
      cells. The DDP increased the ability of TRAIL to SKOV3 cell growth inhibition.
      The apoptotic indexes (AI) of SKOV3 cells detected by FCM were 5.9%, 13.4% and
      39.5% for control group, TRAIL group and TRAIL plus DDP group, respectively. The
      DDP increased the DR5 expressing in SKOV3 cells by 1.95 folds than control group
      and by 1.54 times for the DR4 expressing than the control group (P < 0.05).
      CONCLUSIONS: The soluble TRAIL has the effect on inhibiting the growth of SKOV3
      cells. The combination use of TRAIL and DDP increases significantly the growth
      inhibiting ratio to SKOV3 cells. The AI of SKOV3 cell is raised after TRAIL
      intervening in. The DDP can increase the expressions of DR4 and DR5 in SKOV3
      cells.

PMID- 17037748
TI  - [Expression and localization of estrogen receptor ERalpha and the kinds of ERbeta
      mRNA on placenta].
AB  - OBJECTIVE: To investigate the kinds of ERa, ERbeta mRNA and the localization of
      ERa, ERbeta on normal human placenta. METHODS: The expression and localization of
      ERa,ERbeta on normal human placenta were detected by reverse transcription
      ploymerase chain reaction (RT-PCR) and immunhistochemistry (SP-assay). RESULTS:
      There was mRNA expression of ERalpha and ERbeta on human term placenta, and
      ERbeta was identified with ERbeta5. The ERa immunoreactivity on human term
      placenta was in villous cytotrophoblastic nucleus, and that of ERbeta was in
      syncytiotrophoblastic cytoplasm. CONCLUSION: The findings indicate that ERbeta5
      is the kind of ERbeta on placenta. It is localizated in the cytoplasm of
      syncytiotrophoblast and is probably connected with the production of estrogen.

PMID- 17037749
TI  - [Influence of blockade of costimulation on Th1/Th2 cytokines shift in unexplained
      early recurrent spontaneous].
AB  - OBJECTIVE: To assess the influence of blockade of costimulation on Th1/Th2
      Cytokines shift in unexplained early recurrent spontaneous abortion (URSA).
      METHODS: The levels of IL-2, IFN-gamma and IL-4 were determined by ELISA in the
      supernatant of cultured maternal peripheral blood mononuclear cells (PBMC) from
      30 patients of URSA. Cytokine synthesis was induced by activation with antigens
      from a choriocarcinomer cell line of JEG-3, with CTLA4Ig at concentrations of 10
      microg/mL and 1 microg/mL (experiment groups), or with IgG at the same
      concentrations (control groups). RESULTS: The CTLA4Ig groups showed significantly
      higher levels of Th2 cytokines IL-4 (P < 0.05), lower levels of Th1 cytokines IL
      2 (P < 0.05) and the same levels of IFN-gamma (P > 0.05), compared with the
      control groups of the same concentrations respectively. The same results were
      found between the experiment groups of different concentration. CONCLUSION:
      CTLA4Ig could switch T cell responses from Th1 to Th2 in URSA by blockade of
      CD80/CD86 costimulation.

PMID- 17037750
TI  - [Comparative research on the implantation of mouse blastocyst in the co-cultural
      system of malignant tumor Cells and receptive endometrium in vitro].
AB  - OBJECTIVE: Comparaticely to study biological behaviour variability of mouse
      embryo implantation in vitro between malignant tumor cells and receptive
      endometrium, on the basis of the co-culture of mouse blastocyst and malignant
      tumor cells in vitro. METHODS: The light scope, scanning electron scope, the HE
      and immunohistochemical staining were applied to investigate and observe the
      blastocyst biology behavior in co-cultural system in vitro of mouse blastocyst
      malignant cell and blastocyst-monolayer receptive endometrium. RESULTS: There was
      no significant biological behaviors observed or discovered for mouse blastocysts
      to implant into co-cultural system with malignant tumor cells from different
      histologcial origins, and no significant rates obtained for hatchment, attachment
      and outgrowth of mouse blastocysts in the co-culture system (P > 0.05) of
      monolayer receptival endometrium cells and malignant tumor cells. There was no
      significant difference observed between the cell morphology changes of implanted
      in endometrium and MMP-9 expressed in trophoblastic cells. CONCLUSIONS: That the
      mouse blastocyst cells has no biological behaviour difference happened between
      two co-cultural systems in vitro indicates it may be relevant with its high
      adaptation to environment and self assembly of the early life.

PMID- 17037751
TI  - [A study of genetic diversity in lactate dehydrogenase of Streptococcus mutans
      from clinical isolates].
AB  - OBJECTIVES: Lactate dehydrogenase (LDH) is shown to be an important virulence
      factor resulting in acid production of Streptococcus mutans (S. mutans), on which
      the cariogenic potential of S. mutans depends. Differences in cariogenic
      abilities of S. mutans isolates may be determined by genetic heterogeneity from
      virulent factors. The relationship between LDH activity or genetic diversity and
      cariogenicity of S. mutans (serotype c) isolates was studied in this research.
      METHODS: The genome DNA of S. mutans isolates were isolated and LDH gene (ldh)
      were amplified with specific primers. These isolates came from 34 caries-active
      individuals and 36 caries-free ones, in which 24 strains showed the high LDH
      activity and 21 strains showed the low LDH activity. Then genetic diversity of
      PCR products were analyzed or assessed by restriction fragment-length
      polymorphism (RFLP). Some of amplified LDH genes from different group were
      sequenced and assayed. RESULTS: It is testified that two genotypes A and B of ldh
      RFLP were revealed when LDH genes were digested with Mse I, but Hph I, Mnl I, Dde
      I, Nla III and Alu I digesting fragments of Idh gene did not show different
      pattern. Furthermore, Fisher Exact one-Tail Test showed that the proportion of
      genotype B among strains from caries-free individuals was higher than that from
      caries-active ones (P = 0.033), while the distribution of genotypes with
      different LDH activity was different between two groups (two-Tail Test P =
      0.017). The sequencing DNA testified that the specific base mutation would lead
      to multiple kind of genotype resulted. CONCLUSION: This study indicated that LDH
      gene of S. mutans clinical strains from different individuals is conservative,
      while there still is the gene mutation in. The ldh genetic diversity may be
      related to the low caries sensitivity, and closely correlated with the
      differences in LDH enzyme activity of S. mutans strains.

PMID- 17037752
TI  - [Study on the distribution of lactase in the small intestine of SD rats].
AB  - OBJECTIVE: The article deals with the study on the distribution of lactase and
      its mRNA in the SD rat intestine. METHODS: 15 of the 3-4 wk old SD rats were
      selected for this research project. From SD rat duodenum, we scissored the small
      intestine into 3 segments of each 10 cm length to determine the lactase
      activities and mRNA levels. RESULTS: The lactase activities of all 3 part
      intestines were declined from the duodenum stage by stage (the upper, middle and
      lower segment was 0.179, 0.160, or 0.151 U/ml homogenate respectively, P < 0.05),
      but there were no significant difference of mRNA levels happening among the 3
      groups. CONCLUSION: The results suggest that the lactase activity mainly
      distribute over the upper intestine, although there were lactase along whole
      intestine.

PMID- 17037753
TI  - [Species identification by multiplex amplifying mtDNA-HV I, HV II and cytb
      regions].
AB  - OBJECTIVE: To evaluate the method for species identification by multiplex
      amplification of mtDNA-HV I, HV II and cytb regions. METHODS: The bloodstains or
      muscular tissues of human and 16 kinds of animals were collected. DNA were
      quantified after extraction. Three pairs of primers were mixed in the same
      reaction and the PCR amplification products were analyzed by PAGE and silver
      staining. RESULTS: The presence of three bands (278 bp, 358 bp, 425 bp) indicated
      the samples were from human, while only one band indicated nonhuman origin. The
      position of the animal's only band is different from the band (358 bp) of human.
      CONCLUSION: The method of species identification by multiplex amplifying mtDNA-HV
      I, HV II and cytb regions is simple and sensitive. It is of use for forensic
      identification.

PMID- 17037754
TI  - [The tk gene mutation analysis in WTK1 cell line by multiplex PCR].
AB  - OBJECTIVE: To explore the tk gene mutation spectrum in spontaneous and induced
      WTK1 mutants. METHODS: After exposure to methyl methanesulfonate (MMS), mitomycin
      (MMC) or sodiam azide (NaN3), spontaneously-arising and induced mutants of WTK1
      cell line were selected. The spectrum and hotspot of tk gene mutation were
      analyzed by multiplex PCR. RESULTS: Three chemicals used in this study induced tk
      mutation frequency (MF) to increase significantly in a dose-dependent manner;
      most of the analyzed mutants had lost exon 4 and exon 5-7. CONCLUSION: Three
      chemicals have mutagenic effect on WTK1 cell line, and obvious hotspot exists in
      tk gene mutation.

PMID- 17037755
TI  - [Study on degradation kinetics or potassium dehydroandrographolidi succinas].
AB  - OBJECTIVE: To investigate the hydrolytic degradation of the kinetic
      characteristics of Potassium Dehydroandrographolidi Succinas (DAS-K) in aqueous
      solution. METHODS: The HPLC method was used to determine the degradation kinetic
      parameters of DAS-K aqueous solution at different initial concentration,
      different pH, different ionic strength. various temperatures and in different
      buffer solutions. RESULTS: DAS-K hydrolytic degradation followed first-order
      kinetics as measured by HPLC. From pH 8, the hydrolytic degradation rate of DAS-K
      markedly increased with pH. DAS-K was unstable in alkaline pH solution. The
      species of buffer solutions seem to have different impact on the catalytic
      process. The ionic strength did not have significant effect on the stability of
      the drug. According to the Arrhenius plot, the dependence of the decomposition on
      temperature was a determining factor, the activation energy was estimated to be
      95.68 KJ/mol in phosphate buffer solution at pH 8 and temperature from 60 to 90
      degrees C. CONCLUSION: It was found that the hydrolytic degradation of DAS-K
      complied with first-order kinetics. The rate of hydrolytic degradation of DAS-K
      depended on the pH of solution, the buffer concentration, the buffer species and
      the temperature. Especially, pH value was an important factor in determining the
      rate of the hydrolytic degradation of the drug.

PMID- 17037756
TI  - [Analysis of ordinal repeated measures data using generalized estimating
      equation].
AB  - OBJECTIVE: To explore the application of the generalized estimating equation in
      the ordinal repeated measures data and hence provide methodology reference for
      the analysis of repeated measures data in the clinical trials. METHODS: An
      example was illustrated by modeling generalized estimating equation using the
      GENMOD command in comparison with the independent logistic regression. RESULTS:
      All parameters and their standard error were estimated, so every factor could be
      dealt with intuitive estimation of parameter. The standard errors of coefficients
      in generalized estimating equation are generally greater than that in independent
      logistic regression. CONCLUSION: Generalized estimating equation can solve the
      correlation between the dependent data by using working correlation matrix, and
      it can control strata correlation, repeated measures factor and other confounding
      factors effectively, so generalized estimating equation provides an effective
      method for the ordinal repeated measures data.

PMID- 17037757
TI  - [Establishing a real-time PCR assay for anatid herpesvirus 1].
AB  - OBJECTIVES: To develop a real-time quantitative PCR assay to detect duck plague
      virus (DPV) for the rapid diagnosis of DPV infection, the investigation of its
      nosogenesis and the screening of effective antiviral drugs. METHODS: The primer
      and probe were designed according to the gene sequence of DPV DNA polymerase
      gene. To establish a standard curve, a plasmid containing 125 bp PCR product was
      constructed and severed as a positive control. The TaqMan based real-time PCR
      method was adopted and compared with the traditional PCR approach in sensitivity,
      reliability and specificity. RESULTS: A good linear correlation was demonstrated
      in the standard curve for the real-time PCR assay within the range from 2.3 x 10
      to 2.3 x 10(5) copies. A minimum of 23 positive plasmids could be detected,
      indicating a good sensitivity of the assay. The coefficients of variance (CVs)
      were 1.22-6.69 and 2.09-8.84 for the intra-assay and inter-assay tests
      respectively, indicating a good reliability. No amplification products were found
      for DNA from other pathogens, indicating a good specificity. The comparative
      study proved that the TaqMan technology was much more sensitive than traditional
      PCR assay. CONCLUSION: The real-time quantitative PCR assay for DPV DNA has good
      sensitivity, specificity and reliability.

PMID- 17037758
TI  - [Establishment of the guinea pig model of synovial tuberculosis of knee joint by
      mycobacterium tuberculosis H37Rv infection].
AB  - OBJECTIVE: To explore how to establish the guinea pig model of synovial
      tuberculosis of knee joint by mycobacterium tuberculosis H37Rv infection.
      METHODS: Two doses (1 x 10(7)/mL, 50 microL and 100 microL) of Mycobacterium
      strains were injected into the knee joint of the guinea pig that had been
      immunized and allergized with Freund's complete adjuvant six weeks previously.
      The pathological changes of the synovial membrane, cartilage and bone after
      infection of mycobacterium tuberculosis were investigated. At the same time, the
      synovial membrane tissues and culture for the mycobacterium tuberculosis were
      collected and examined. RESULTS: After the infection of mycobacterium
      tuberculosis H37Rv, the knee joint of guinea pig became swollen, but the
      interference to the whole conditions of the guinea pig was slight in both
      infection groups. The tissue sections of the synovial membrane showed tubercle
      and caseous necrosis of the knee joint in both groups. The mycobacterium
      tuberculosis could be detected by using Ziehl-neelsen stain and the culture from
      the synovial membrane of the knee joint. CONCLUSION: By injecting suitable dosage
      of mycobacterium H37Rv strains into the joint of the immunized and allergized
      guinea pig, we have established the guinea pig model of synovial tuberculosis
      that is pathologically similar to synovial tuberculosis in humans, so it is fit
      for use in the diagnostic studies and pathological researches.

PMID- 17037759
TI  - [Obesity and nutrition disorders].

PMID- 17037760
TI  - [Bariatric surgery].

PMID- 17037761
TI  - [Child nutrition].

PMID- 17037762
TI  - [Malabsorption and celiac disease].

PMID- 17037763
TI  - [NSAIDs or coxibs: benefits and gastrointestinal vs. cardiovascular effects].

PMID- 17037764
TI  - [Gastric cancer].

PMID- 17037766
TI  - [Pancreatitis].

PMID- 17037765
TI  - H. pylori: scientific basis to patient cure.

PMID- 17037767
TI  - [Diagnostic and therapeutic endoscopy of pancreas and biliary tract].

PMID- 17037768
TI  - [Gallbladder and Bile Ducts].

PMID- 17037769
TI  - [Pancreatic neoplasms].

PMID- 17037770
TI  - [Hemostasis in gastrointestinal hemorrhage].

PMID- 17037771
TI  - [Endoscopic ultrasound 2006].

PMID- 17037772
TI  - [Obscure gastrointestinal bleeding].

PMID- 17037773
TI  - [Diagnostic advances in gastroesophageal reflux disease].

PMID- 17037774
TI  - [Non-erosive gastroesophageal reflux disease].

PMID- 17037776
TI  - [Barrett esophagus].

PMID- 17037775
TI  - [Medical therapy of gastroesophageal reflux disease].

PMID- 17037777
TI  - [Surgical treatment of gastroesophageal reflux disease].

PMID- 17037778
TI  - [Risk reductions in gastroenterology].

PMID- 17037779
TI  - [Functional dyspepsia].

PMID- 17037780
TI  - [Heartburn and chest pain].

PMID- 17037781
TI  - [Irritable bowel syndrome].

PMID- 17037782
TI  - [Functional constipation].

PMID- 17037783
TI  - [Digestive system functional disorders in children].

PMID- 17037784
TI  - [Chronic diarrhea].

PMID- 17037785
TI  - [Advances in the use of non-biologic agents in the treatment of inflammatory
      bowel diseases].

PMID- 17037786
TI  - [Biologic therapy for inflammatory bowel diseases].

PMID- 17037787
TI  - [Colorectal cancer].

PMID- 17037788
TI  - [Autoimmune hepatitis].

PMID- 17037789
TI  - [Hepatitis C and B (HCV, HBV)].

PMID- 17037790
TI  - [Non alcoholic fatty liver].

PMID- 17037791
TI  - [Liver transplantation update 2005-2006].

PMID- 17037792
TI  - [Genomic medicine and hepatology].

PMID- 17037793
TI  - [The future of radiology].

PMID- 17037794
TI  - [Hepatic insufficiency and related factors].

PMID- 17037795
TI  - [Medical therapy of portal hypertension].

PMID- 17037796
TI  - [AGA plenaries].

PMID- 17037797
TI  - [ASGE pleanry session].

PMID- 17037798
TI  - [SSAT plenary session].

PMID- 17037799
TI  - [Neonatal mortality in a regional perinatal hospital in Merida, Yucatan, 1995
      2004 I. Analysis of the gross, specific rates].
AB  - OBJECTIVE: To evaluate the neonatal mortality and the specific neonatal mortality
      rates by groups of birthweight and gestacional age, at the Ignacio Garcia Tellez
      National Medical Center which is a reference tertiary perinatal center of the
      Social Security Mexican Institute for the Yucatan Peninsula, along the period of
      1995-2004. MATERIAL AND METHODS: A cohort of 46,297 live newborns was studied
      with birtweight of 500 grams or more, that were discharged between January 1st
      1995 and December 31st 2004. Birthweight, gestational age, length of
      hospitalization, condition at discharge were captured in a data base. Triennial
      analysis of mortality was done. RESULTS: The proportion of neonates with
      birthweight <2,500 g increased and 19% neonates <1,000 g 50%, the increment was
      21% for preterm neonates, 46% for immature, and 40% for those extremely immature.
      The early neonatal mortality rate diminished from 7.0 to 6.9, the late mortality
      from 3.0 to 2.2, the neonatal from 10.0 to 9.2/1,000 live newborn, the survival
      increased 232% in neonates with birthweight between 500-749 g, 25% between 750
      999 g, 5.8% between 1,000-1,249 g, 8.2% between 1,250-1,499 g. The neonatal
      mortality decreased 31.8% from the expected, because the adjusted neonatal
      mortality rate was 13.5 compared with the observed 9.2/1,000 live newborn.
      CONCLUSIONS: There was a significant increase of the survival with lesser
      birthweight and gestational age, although it was not reflected in the brut
      neonatal mortality rate because there was an increase of the risk population.

PMID- 17037800
TI  - [Prescription and drug expenditure in gynecology and obstetrics in Northwest
      medical units from IMSS].
AB  - BACKGROUND: Drug prescription is the most frequent medical intervention in
      Gynecology and Obstetrics; however, studies of prescription profile are limited.
      In this study, we analyzed differences of expense by drug prescription for
      gynecologic and obstetrics health problems. PATIENTS AND METHOD: It was performed
      a cross sectional study for one year analysis in each medical area that shape
      IMSS western district. We calculated spending and consumption coefficients for
      each drug and therapeutic groups. User coefficients were ordered to compare
      consumption differences. Besides the statistical ratio of consumption between
      drugs groups, we described the differences found and analyzed the prescription
      profile among medical regions. RESULTS: Data related to the expenses in each one
      of the regions show important differences in each one of the drugs and
      therapeutic groups. The most common expense for drugs is related to the treatment
      of osteoporosis, menopause and fertility problems. We also found differences in
      prescription drug preferences in each therapeutic subgroup. DISCUSSION: Drug
      prescription studies are useful as a basis for further specific studies in each
      pharmacologic subgroup. There are few studies that analyze the drug prescription
      profile on Gynecology and Obstetrics. In this study it is possible to suppose
      that medical prescription was not based on known medical evidences; therefore, we
      must reconsider the need of a permanent actualization and systematic medical
      evaluation.

PMID- 17037801
TI  - [Anal incontinence caused by an obstetric trauma. Experience with the technique
      of overlapping sphincteroplasty].
AB  - INTRODUCTION: Anal incontinence (IA) could be of idiopathic, congenital,
      neurological origin, or secondary to trauma. Obstetric trauma is the most common
      cause of the traumatic anal incontinence. OBJECTIVE: To analyze results of a
      group of patients with anal incontinence secondary to obstetric trauma, with
      overlapping sphincteroplasty. PATIENTS AND METHODS: All patients with anal
      incontinence secondary to obstetric trauma without neurological damage, between
      January 2002 to January 2006 were studied; all of them underwent overlapping
      sphincteroplasty. We evaluated improvement in incontinence score according Jorge
      and Wexner incontinence scale, pre and postoperatively as well as morbi-mortality
      rates. RESULTS: 16 patients, most of them with total anal incontinence, with
      preoperative values between 16 to 20 points at the Jorge and Wexner scale; 14
      patients (87.5%) referred improvement in their values with 4 to 0 points
      postoperatively, two patients did not refer significant improvement, both of them
      with defects in both sphincters and loss of the 50% of the entire sphincteric
      complex. They were sent to bio-feedback therapy. There was not mortality. Seven
      patients (43.7%) had skin dehiscence. CONCLUSIONS: Overlapping sphincteroplasty
      is an accurately technique for repair obstetric trauma injuries of the anal
      sphincter, with a success rate of 70 to 80%, and a low morbidity rate.

PMID- 17037802
TI  - [Mozart's music in the prenatal period].
AB  - Diverse studies demonstrate that the future baby reacts to the sounds and the
      light in uterus four months before being born, that is to say, he is able to
      recognize stimulus which was exposed habitually, like the beats of the mothers
      heart and the voice of the same one when talk him before being born, likewise the
      music he used to heard during pregnancy. The babies who through their mother
      listened to music of Mozart in uterus and return it to listen in the delivery
      room of when they are born feel greater tranquility and less aggressiveness.
      Mozart was a genius and the most beautiful from it is the so important impact in
      the cognitive development, social and affective of those who are exposed to the
      wonderful sounds and rythm of music from the maternal belly. The previous thing
      is based on experiments scientifically controlled that revalue the communication
      between the mother and the future baby as well as the importance of this link.

PMID- 17037803
TI  - [Physician-patient relationship: a forgotten need?].
AB  - The medical-patient relation has a big weight in the medical practice. There have
      been different medical codes that highlight the importance of this relation and
      the existence of the patient's rights; nevertheless, its repercussion has been
      scarce. A few time ago, this relation was established among a clear binomial: the
      doctor and the patient, but now this binomial is very complex and it seems to
      have disappeared. The main models of the medical-patient relation are: Activity
      Passiveness, Guide-Cooperation, and Participation. Currently, the medical-patient
      relation has been deteriorated because it was interfered by external factors,
      such as: socioeconomic problems, those due to the technological development and
      those attributable to the doctor's conduct. It seems fundamental to recover this
      relation, as a part of the medical art. The solution is not easy and involves the
      need to count with legal mechanisms that protect the doctors and patients rights.
      Besides, it will be important to carry out deep changes in the models of health
      education. If the medical-patient relation is not prioritized as an important
      part of the medical exercise, our profession would face the risk of only becoming
      a technical occupation.

PMID- 17037804
TI  - [Uterine and jejunum perforation due to intrauterine device. A report of a case
      and literature review].
AB  - The application of a copper IUD can perforate completely the uterus and involve
      adjacent organs such as the bladder, small bowel, colon, rectum or appendix. Once
      the diagnosis is established, complete extraction must follow. We present a case
      report of a 33 year-old patient in which a copper IUD was placed in a medical
      office, three months after a third cesarean, without history of sepsis. Ninety
      days after placement, the patient complained of menstrual irregularities
      (opsomenhorrea) without any other symptoms. On physical examination with
      speculum, the IUD's guide strings were not visible; a transvaginal USG was
      performed without visualization of the IUD in the uterine cavity. An abdominal
      CAT scan showed the presence of the IUD outside the uterus. Hysteroscopy
      laparoscopy was performed with transoperatory fluoroscopy, which revealed the
      copper IUD inside the yeyunum, a complete extraction followed with entero-entero
      anastomosis. This case will show that IUD placement is not innocuous and that
      adjacent organ damage must always be considered and resolved immediately.

PMID- 17037805
TI  - [Ectopia cordis: multidisciplinary approach with successful result].
AB  - Ectopia cordis is a pathology in which the heart is complete or partially outside
      of the thoracic cavity. It represents a challenge for the diagnosis and handling
      because of its high perinatal mortality. We present the first case of thoracic
      ectopia cordis with prenatal diagnostic (27th week), its multidisciplinary
      handling at Hospital de Ginecopediatria num. 71 of the Centro Medico Nacional
      Adolfo Ruiz Cortines, IMSS, in Veracruz, Mexico. We communicate the case of a 24
      year-old woman referred by her correspondent medical unit with the diagnosis of
      23.6 weeks pregnancy with suspicion of heart malformation by ultrasound. The
      pregnancy was followed-up until the 38th week, when it was programmed a caesarean
      section. The newborn had ectopia cordis, which was treated at the moment of
      birth. In this article, we present pictures of the heart defect as well as its
      evolution. The up-to-date bibliography is revised about the medical profile and
      treatment. The handling of the ectopia cordis includes an appropriate prenatal
      diagnosis through echocardiograph, a multidisciplinary perinatal team, to program
      the caesarean operation, aseptic handling of the newborn, immediate correction of
      the wall defect with skin torn piece without trying to correct the costal grill,
      specific hemodynamic cares, to reprogramme a correction of associated defects.

PMID- 17037806
TI  - [Clinical results of the use of high doses of diethylstilbestrol on abortion
      threat. 1951].

PMID- 17037807
TI  - [Working memory: neuropsychological and neurobiological issues].
AB  - Working memory denotes an ability to remember information for a short-time and to
      manipulate it. The memory allows including correct information depending on the
      situation, to keep the information on present activities for a while and enables
      changing the reaction according to new criteria. The relation between working
      memory and efficiency of complex cognitive processes and also with the control of
      emotional processes, plasticity of behaviour and consciousness was demonstrated.
      Working memory is connected with the activity of the dorsolateral prefrontal
      cortex of the brain. Recently, it has been shown, that working memory
      disturbances play an important role in the aetiopathogenesis of psychiatric
      disturbances such as schizophrenia, bipolar affective disorder or obsessive
      compulsive disorder. Working memory disturbances are also shown in a proportion
      of healthy first-degree relatives of patients with schizophrenia or bipolar
      disorders. Working memory disturbances are presently regarded as a cognitive
      endophenotypic marker of vulnerability to these illnesses. In recent years, an
      association between working memory abilities and activity of different
      neurotransmitters, especially with the dopaminergic system in the brain, has been
      shown. Molecular genetic studies show an association between working memory
      abilities and polymorphism of the dopaminergic system genes in schizophrenia and
      polymorphism of BDNF gene in bipolar affective disorders. So far not much data
      about the genetics of working memory in healthy subjects has been gathered.
      Currently in Poland such research is carried on in the Clinical Neuropsychology
      Unit Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz in
      cooperation with the Department of Adult Psychiatry and Laboratory of Psychiatric
      Genetics University of Medical Sciences in Poznan.

PMID- 17037808
TI  - [Evolutionary concepts of affective disorders].
AB  - Mood may be considered the module of the human mind, which has evolved to tune
      the activity ofthe organism to the specific environmental conditions in a better
      way. In some cases depression may be adaptive, for example in aborting the
      activity associated with too many obstacles. At the same time hypomania may be
      related to the capability of mobilising the organism to gain many resources in a
      short period of time. Severe mood disorders may be related to the genetic
      variants, eg. of the serotonin transporter or brain-derived neurotrophic factor,
      which in several situations may give some evolutionary advantage. Affective
      temperaments, observed in the relatives of patients with affective disorders may
      be associated with some benefits in the social life. The relationship between
      early adversities and adult depression may be related to the phenomenon of the
      stress axis programming, which has deep evolutionary roots. Some infectious
      factors may cause behaviours similar to the affective symptoms, which may
      increase their reproductive success. The evolutionary perspective, which is
      complementary to the current etiopathogenic theories may help in understanding,
      why genes and traits which

PMID- 17037809
TI  - [Serotoninergic system and limbic-hypothalamic-pituitary-adrenal axis (LHPA axis)
      in depression].
AB  - Depression is associated with the dysfunction in the serotoninergic (5-HT, 5
      hydroxytryptamine) transmission and dysregulation of the limbic-hypothalamic
      pituitary-adrenal axis (LHPA axis). In depression, the 5-HT system exhibits
      impaired presynaptic activity of 5-HT neurones, an increased activity of central
      postsynaptic 5-HT2A receptors, decreased activity of postsynaptic 5-HT1A
      receptors and altered synaptic 5-HT uptake. The coexistent dysregulation of the
      LHPA axis is predominantly linked to GR (glucocorticoid receptor) dysfunction
      within the limbic system along with hypercortisolemia, MR (mineralocorticoid
      receptor) and GR receptors imbalance which results in impaired negative feedback
      mechanisms in the LHPA axis loops. Several clinical and animal studies revealed
      the involvement of 5-HT1A system in LHPA axis regulatory mechanisms. That
      association seems to be dependent on the corticoid levels. The impaired GR
      receptor function and MR/GR receptors imbalance alter the negative feedback
      regulation within the LHPA axis which is followed by its dysregulation and
      hypercortisolemia that is further associated with the decreased activity of
      postsynaptic 5-HT1A receptors resulting in a serotoninergic dysfunction. The aim
      of this paper is to discuss and review the current data on the existence of the
      hypothetical relationship between the activity of the serotoninergic system,
      predominantly 5-HT1A receptors, and LHPA axis in depression.

PMID- 17037810
TI  - [Indicators of the persistent pro-inflammatory activation of the immune system in
      depression].
AB  - The aetiology of depression remains tentative. Current hypotheses on the
      aetiology of the depressive disorder tend to integrate monoaminoergic,
      neuroendocrine and immunological concepts of depression. A number of research
      papers emphasise the altered hormonal and immune status of patients with
      depression with pronounced cytokine level variations. Those studies tend to link
      the variable course of depression in relation to the altered proinflammatory
      activity of the immune system. The results of the studies on the activity of the
      selected elements of the immune system are ambiguous indicating both increased
      and decreased activities of its selected elements. However, a number of basic and
      psychopharmacological studies support the hypothesis of the increased
      proinflammatory activity of the immune system in the course of depression which
      is the foundation for the immunological hypothesis of depression. The aim of this
      paper is to review the functional abnormalities that are observed in depression
      focusing on the monoaminoergic deficiency and increased immune activation as well
      as endocrine dysregulation. This paper puts together and discusses current
      studies related to this subject with a detailed insight into interactions
      involving nervous, endocrine and immune systems.

PMID- 17037811
TI  - [The probability of bipolarity among patients with recurrent depressive
      disorder].
AB  - Over the last few years researchers have paid a lot of attention to the problem
      of the correct diagnosis of affective disorders. Propositions have appeared
      regarding the widening of the officially accepted criteria to be used in
      diagnosis. AIM: The aim of the study was to assess the probability of various
      types of bipolar affective disorders (type 1 and 2 CHAD, as well as spectrum)
      among patients (n = 246) treated for recurrent depressive disorder (CHAJ).
      METHOD: The analysis was based on the broadened criteria for affective disorders
      introduced by Ghaemi et al. and Hirschfield's Questionnaire on affective
      disorders. RESULTS: The appearance in the past of strange, risky behaviour was
      associated with a greater risk of type 1 CHAD in comparison to CHAJ (OR=24.5), as
      did extreme, irrational expenditure (OR=21. 1), a lack of criticism with respect
      to one's own social behaviour (OR=20.3), increased interest in sex (OR=17.7), as
      well as extreme self confidence (OR=12). A lack of criticism with respect to
      one's own social behaviour and strange, risky behaviour was associated with a
      greater risk of type 2 CHAD (OR=12.7 and OR=10, respectively). The greatest risk
      of spectrum CHAD type disorders were associated with hypomania, including drug
      induced (OR=15.8). as well as a lack of criticism with respect to one's own
      social behaviour (OR=11.8). Panic attacks appeared more often in bipolar
      affective disorders in comparison to recurring depressive disorders, but their
      frequency was similar in all three groups (CHAD-I, CHAD-II, CHAD-S). The early
      occurrence of depression (before 25 years of age) increased the risk of each of
      the three types of bipolar affective disorders significantly (by a factor of 3 to
      5). CONCLUSIONS: The findings indicate the necessity of discussion on sharp
      criteria of bipolar affective disorders. The results should be helpful in the
      diagnosis of such disorders, which could have important consequences for
      effective therapy.

PMID- 17037812
TI  - [Comorbidity of eating disorders and bipolar affective disorders].
AB  - Eating disorders--anorexia nervosa, bulimia nervosa and eating disorders not
      otherwise specified (EDNOS) occur usually in young females. The significant
      pathogenic differences between patients who only restrict food, and patients with
      binge eating and compensatory behaviours, such as vomiting and purging were
      described. The prevalence of bipolar affective disorders--especially bipolar II
      and bipolar spectrum disorders (BS) may reach 5% in the general population. About
      half of the depressive episodes are associated with a "mild" bipolar disorder,
      and such a diagnosis is suggested by impulsivity and mood-instability.
      Previously, majority of research on the comorbidity between eating and affective
      disorders focused on depressive symptomatology, however difficulties in the
      reliable assessment of hypomania may obfuscate the estimation of the co
      occurrence of eating disorders with BS. Epidemiological studies suggest the
      association between BS and eating disorders with binge episodes (bulimia nervosa,
      anorexia- bulimic type and EDNOS with binge episodes). Co-occurrence of such
      disorders with depressive symptoms probably suggests the diagnosis of BS, not
      recurrent depression. Bulimic behaviours, impulsivity and affective disorders
      might be related to the impairment of the serotonergic neurotransmission, which
      may result from the genetic vulnerability and early life trauma. Currently, the
      first-line pharmacological treatment of co-occurring eating disorders with binge
      episodes and BS are selective serotonin reuptake inhibitors. However in some
      cases, the use of mood-stabilising agents as monotherapy or in combination with
      serotonergic drugs may be helpful.

PMID- 17037813
TI  - [Point prevalence of depression in the Cracow population of 13 year old students
      in 1984 and 2001].
AB  - Results of scarce epidemiological studies on depression in adolescents are
      diverse and dependent of survey methodology as well as on the theoretical
      approach of research. Those studies where the methods are comparable show that
      depression prevalence depends on the macrosocial situation and the adolescence
      stage. AIM: The study aimed to assess changes in depression prevalence in mid
      adolescents between 1984 and 2001. A presumption was made that the social
      situation in Poland had changed in the last 17 years. METHOD: In 2001 a
      representative sample of school attending 13 y.o. adolescents was screened with
      KID-IO "B1". The results were compared with those of a similar survey, using the
      same method, carried out in 1984. RESULTS: Point prevalence index in 2001
      appeared to be lower than in the survey in 1984 (24.6% versus 31.6%). This
      resulted exclusively from a significant decrease in depression among girls (26.8%
      versus 42.2%). CONCLUSION: The obtained data allows for an interpretation of the
      findings as being a result of macrosocial changes. Other hypotheses e.g.
      influence of the adolescence timing and course requires a longitudinal
      prospective study.

PMID- 17037814
TI  - [Prospective studies on dynamics of depression from preadolescence to early
      adolescence].
AB  - AIM: The aim of the study is to evaluate the changes in prevalence and dynamics
      of depression during puberty. It was conducted in prospective studies in a
      representative group of large-town primary school students. METHOD: A group of
      1993, 10 year-old students were chosen in a two-stage draw. They were studied
      with the Karkow Depression Inwentory (KID) in the subsequent years 2001, 2002,
      2003. RESULTS: The point prevalence of depression was respectively 29%, 30% and
      26% for 10, 11 and 12 year-olds. The spread-out rate of depressive disorder was
      relatively stable. CONCLUSIONS: Depression is more common in pre-adolescent boys
      than girls. The dynamics of the disorder, when studied in these three years show
      that depression is a disorder with a very unequivocal course amongst the
      preadolescents.

PMID- 17037815
TI  - [Coping with stress strategies among female patients suffering from a
      depression].
AB  - INTRODUCTION: Within the past few years there was an ever increasing number of
      scientific publications focusing on the question of stress, new theories were
      created as well as efforts were taken to classify them. According to stress
      researchers, finding out how to manage with stress and with difficulties (the
      strategy of coping) plays an even more important role than the phenomenon of
      stress itself. This is due to the fact that the former decides about the quality
      of one's life. Stressful transactions in the aspect of a disease seem to differ
      from everyday stressful problems. The intensity of stress and the capability of
      taking control over stress itself are different in the case of a danger of
      disease compared to an experience of disease, which influences applying certain
      coping strategies (task-aimed strategies). AIM: The purpose the study was to
      determine the relationship between the social functioning of female patients
      suffering from depression with their coping style. METHOD: 60 female patients
      with a diagnosed depression and 60 mentally ordered female patients were tested
      with the use of Endler's and Parker's Coping Inventory for Stressful Situations
      Questionnaire (CISS). RESULTS: The study presents and describes the result of the
      research concerning female patients suffering from depression. The analysis of
      the results indicated the existence of differences in choosing coping strategies
      (task-aimed strategies) in both the studied groups of women. CONCLUSIONS: The
      study shows that female patients with depression cope with stress mostly using
      emotional strategies, and the avoidance strategies are used the least often.
      Mentally ordered women however, most commonly use problem (task)-focused
      strategies.

PMID- 17037816
TI  - [The level of social support parameters in relation to coping with stress caused
      by a disease among female patients suffering from depression].
AB  - INTRODUCTION: Social support issues have their permanent position in the studies
      of socio-psychological changes influencing people's health. Social support has
      been treated as one of the factors guarding against disease symptoms occurrence
      and supporting the stable health state. AIM: The purpose the study was to
      determine how female patients suffering from depression function in society in
      relation to the social support they receive. METHOD: 60 female patients with a
      diagnosed depression and 60 mentally ordered female patients were tested with the
      use of Uchnast's Sense of Security Questionnaire (KPB). The social support
      aspects such as the sense of security, sense of closeness, stability and self
      confidence were analysed. The participants of the analysis were both women with
      diagnosed depression and women without any indicators of a depression. RESULTS:
      The analysis of the result indicated the existence of differences in the
      intensity of all the social support parameters in both studied groups of women.
      CONCLUSIONS: Women with depression are characterised by a lower sense of
      closeness, lower stability and lower self-confidence. Among the female patients
      with depression there is a lower level of the need of safety, and this is the
      symptom characteristic for the individuals not properly adjusted to social
      conditions. Lower sense of security staunches and deteriorates the perception of
      social support, both perceived and expected.

PMID- 17037817
TI  - [The eclectic individual psychotherapy of a dysthymic patient--case study].
AB  - The article describes the case of eclectic individual psychotherapy of a
      dysthymic patient. The therapeutic process integrated elements of the following
      psychotherapeutic approaches: psychodynamic, behavioural-cognitive, systemic,
      interpersonal, existential and Gestalt. The paper discusses history of treatment,
      diagnosis of dysthymia, indications for psychotherapy, course of the sessions.
      Anamnesis, factors contributing to the disorder, triggers and factors sustaining
      the symptoms, personality factors were also analysed. Therapeutic goals and
      applied techniques are presented.

PMID- 17037818
TI  - [The stroke variables assessment as a prognostic factor for post-stroke
      depression with the emphasis on the cerebral SPECT regional blood flow
      asymmetry].
AB  - AIM: The aim of this paper was to assess the risk for depression in a 6-month
      long post stroke follow up period as related to the stroke variables (i.e. stroke
      localisation, haemodynamic parameters). METHOD: The stroke localisation was
      determined with CT and/or MRI. Subsequently all the examined individuals
      underwent SPECT examination. The follow up examinations were performed by the
      consultant psychiatrist in 6, 12 and 24 weeks subsequent to the stroke episode.
      The depressive episode diagnosis was established on the basis of ICD-10
      diagnostic criteria. RESULTS: Only right-handed patients (43 men aged 57.3 +/-
      11.6 and 17 women aged 62.5 +/- 14.4) with unilateral brain lesion were examined.
      23 subjects (38%) developed depression in the follow-up period. 5 women (29%) and
      18 men (ca. 42%) developed a depressive episode. Only one of the observed
      depressive episodes met ICD-10 criteria for severe depressive episode. 10
      patients suffered from moderate depressive episode and 12 subjects exhibited a
      mild depressive episode. CONCLUSIONS: The results obtained with CT and/or MRI
      techniques revealed no correlation between the post-stroke depression and stroke
      lateralisation. However the localisation of the deep brain functional
      abnormalities revealed with SPECT correlated with the occurrence of the affective
      disorders as related to the asymmetry in regional blood flow measures.

PMID- 17037819
TI  - [Changes of coefficients of sleep onset, sleep maintenance and awakenings in most
      common psychiatric disorders in inpatients].
AB  - INTRODUCTION: The study's purpose was to find differences of selected
      psychopathological syndromes according to characteristic disturbances of sleep
      which are present in them. METHODS: Among 194 patients (mean age: 42.27 +/-
      14.15) 108 were women (mean age: 42.97 +/- 14.13) and 86 were men (mean age:
      41.38 +/- 14.22). Psychiatric examination and sleep disturbance evaluation was
      done with the use of our own questionnaire: Multidimensional System for
      Evaluation of Sleep Disorders (MSESD) were performed the third day after
      admission to a psychiatric ward. Sleep was analysed according to coefficients
      which described falling asleep, sleep maintenance and awakenings. These
      coefficients were created according to parameters obtained from MSESD. RESULTS:
      Coefficients obtained from the "schizophrenic disorders" and "personality
      disorders" groups did not differ significantly from the average coefficients for
      all the patients. The common feature among other groups of patients was the
      elevation of the coefficient of falling asleep especially for the "organic" and
      "depressive" disorders groups. The most pronounced elevation of the falling
      asleep coefficient was detected in the "depression without somatic features"
      group, however this elevation was also clearly seen in the "reactive disorders"
      group. In the latter group all other coefficients were also significantly
      elevated. CONCLUSIONS: Constructed coefficients of sleep disturbances may be
      useful for diagnosing and differentiating the most often psychiatric disorders in
      inpatients.

PMID- 17037820
TI  - [Pharmacological treatment of insomnia].
AB  - Sleep disturbances of insomnia type belong to the most common health problems of
      the modern society. Chronic insomnia, one that worsens daytime functioning and
      lasts over one month, occurs in 9 to 15% of the general population of developed
      countries. Further 15-20% of the population suffers from short term insomnia.
      When approaching a patient with insomnia, the physician should firstly regard
      sleep disturbances as a symptom related to other medical conditions. The most
      common causes of chronic insomnia include psychiatric disorders, addictions,
      somatic disorders and poor sleep habits. For successful treatment of insomnia it
      is most important to diagnose the cause of sleep problems properly. Such
      management of sleep disturbances allows treating insomnia causally. The
      symptomatic treatment of insomnia includes sleep hygiene and intermittent
      administration of sleep promoting drugs such as benzodiazepines, non
      benzodiazepine hypnotics of second generation, antidepressants, antipsychotics,
      antihistaminics or herbal and over the counter agents. This article reviews the
      sleep promoting drugs and substances that can be used for treatment of chronic
      insomnia.

PMID- 17037821
TI  - [A double-blind controlled study of the efficacy and acceptability of tianeptine
      in comparison with fluvoxamine in the treatment of depressed alcoholic patients].
AB  - AIM: The main objective of the study was the evaluation of therapeutic efficacy
      of tianeptine (T) (37.5 mg/day) in comparison with fluvoxamine (F) (100 mg/day)
      in depressed patients with alcohol dependence or harmful use who had abstained
      from alcohol, in a 6-week treatment period. The secondary objectives were the
      assessment of the acceptability of both drugs and analysis of the alcohol craving
      behaviour regarding both treatments. METHOD: Outpatients who met ICD-10 criteria
      for depression and alcohol dependence or harmful use were randomised to a double
      blind 6-week comparative trail. Responders (50% or more reduction in baseline
      HDRS) were proposed to continue the same treatment up to 90 days. The
      antidepressant efficacy was assessed with the use of the HDRS (main criterion).
      Other scales used in the study were HARS, CGI and OCDS. Tolerance was evaluated
      by monitoring of adverse events. RESULTS: A total of 298 (150 in T group and 148
      in F group) were randomized. Both drugs showed good efficacy in the treatment of
      depressive symptoms. In Full Analysis Set (FAS) mean HDRS score significantly
      decreased in both groups from 22.2 at baseline to 10.6 at end-point in T group
      and from 21.8 to 11.4 in F group. There was no statistical difference between
      groups. The number of patients found to be responders at end-point was 72.1% in
      the T group and 67.1% in the F group. There was significant improvement in both
      treatment groups in HARS and CGI. Also analysis of alcohol craving by the OCDS
      scale showed significant improvement in both groups. No significant difference
      between treatment groups regarding those scales was noted. In a 6-week treatment
      period, statistically significantly more patients continued the study in the T
      group. Tolerability of both drugs was good. 16.7% of the patients experienced at
      least one adverse event in the T group and 20.3% in the F group. CONCLUSION:
      Tianeptine and fluvoxamine are effective and safe in the treatment of depression
      in the group of patients with alcohol dependence.

PMID- 17037822
TI  - [New and traditional laboratory markers of alcohol abuse in hospitalized alcohol
      dependent men].
AB  - AIM: Evaluation of the diagnostic value (sensitivity, specificity and accuracy)
      of the new-carbohydrate-deficient transferrin (CDT), sialic acid (SA) and
      traditional (GGT, AST, ALT and MCV) markers of alcohol abuse in alcohol dependent
      men irrespective of the time of abstinence. METHOD: 75 alcohol dependent men
      admitted for treatment have been tested. The examination was performed twice:
      upon admission to the hospital and after 3 weeks of hospitalization. CDT was
      estimated using an immunoturbidimetric assay after anion-exchange chromatography
      and sialic acid by the enzymatic colorimetric method. The diagnostic accuracy was
      calculated as the area under the ROC curve (AUC). RESULTS: At the time of
      admission to hospital, the values of CDT and sialic acid were elevated in
      comparison with the control group, similarly as with the traditional tests. After
      3 weeks of hospitalization all test results decreased. CDT correlated positively
      with AST and sialic acid with ALT and GGT. The highest diagnostic accuracy was
      obtained for CDT (AUC=0.89). The diagnostic accuracy of sialic acid was lower
      than MCV, GGT and AST, but the same as ALT (AUC=0.66). CONCLUSIONS: CDT exhibits
      the highest diagnostic usefulness for alcohol abuse in alcohol dependent men in
      different time of abstinence. The tests with high diagnostic accuracy (CDT, MCV
      and GGT) are still useful after 3 weeks of hospitalization (abstinence), when the
      remaining tests are normalized.

PMID- 17037823
TI  - [Private and public self-awareness changes in psychotherapy of alcohol-addicted
      felons].
AB  - AIM: Testing effectiveness of psychotherapy by evaluating changes in private and
      public self-consciousness of alcohol addicted persons and imprisoned felons.
      METHOD: The questionnaire known as Self-Consiousness Scale Fenigstein, Scheier,
      Buss's was applied. The tool is based on the theory of Duval and Wicklund and
      that of Carver and Scheier. Treatment curriculum--was based on two models of
      alcohol addiction. the psychological one and the other derived of assumptions
      defined in the Alcoholics Anonymous movement. RESULTS: In the course of the
      psychotherapeutic treatment--discordantly with prior research expectations-
      neither the so-called private nor the public self-consciousness changed. In turn,
      as hypothesised, social anxiety decreased significantly. CONCLUSIONS: 1. Decrease
      of social anxiety shows effectiveness of the therapeutic approach, which is
      higher than that of the sole Alcoholics Anonymous programme. 2. Further research
      should be focused on refinement of both the tool measuring self-consciousness
      changes and some elements of the therapeutic agenda.

PMID- 17037824
TI  - [Security measures in the penal code, in the opinions of expert psychiatrists and
      some problems in their applications].
AB  - The aim of this paper is to remind expert psychiatrists, the three basic elements
      required for the application of security measures such as placing the convict in
      a psychiatric hospital. They are: 1) An act was of serious social damage, 2) the
      damage was committed in a state of non-liability, 3) there is a high risk of the
      person repeating the act of similar social damage. The fulfilment of these three
      is an obligation for the court to apply the security measure of placing the
      person in a psychiatric hospital (art. 94 section 1 of the penal code). Practice
      shows that experts have difficulties in these evaluations, which in turn results
      in faults in directing for placement withoutjust cause, or in turn-there is no
      directing, even though there are causes for it. There is a huge need for legal
      regulations on these manners, after the forensic psychiatric observation ends.
      The non-liable delinquent who committed an act of serious social damage is in
      risk of committing this act once more, whilst he is not in custody. The issue is
      in showing a legal basis for keeping the non-liable delinquent from such an act
      in a psychiatric hospital, in spite of ending the observation, until the legal
      sentence on the security measure is in place.

PMID- 17037825
TI  - Charity with an arm twist. Senate hearing starts the ball rolling on tougher
      community benefits standard, greater federal oversight of not-for-profits.
AB  - A Senate hearing last week helped boost not-for-profit hospitals' chances of
      facing a new standard for reporting community benefits. At stake for hospitals
      are billions in tax breaks. The standard for exemption hasn't been modified since
      1969, and "has not kept up with the substantial unfunded health needs of
      communities," says Nancy Kane, right, a member of MedPAC.

PMID- 17037826
TI  - Executive privilege. Club dues called business expense.

PMID- 17037827
TI  - AHA: transparency our way OK. Association backs bill similar to its initial
      proposal.

PMID- 17037828
TI  - Questioning technology. Calif. Blues' foundation grant spearheads research.

PMID- 17037829
TI  - The bash brothers. Grassley, Stark wasting capital with continuous attacks on
      providers.

PMID- 17037830
TI  - 2006 up and comers. Twelve young leaders use their energy and enthusiasm to make
      a difference.

PMID- 17037831
TI  - Nanostructured biofilms and biocrystals.
AB  - The design, the physical properties and the implementation of nanostructured
      protein biofilms and nanostructured biocrystals are here summarized from ab
      initio considerations. Particular emphasis is placed on those being developed in
      our Institute having unique properties useful in a wide range of applications.

PMID- 17037832
TI  - Nanopatterns with biological functions.
AB  - Both curiosity and a desire for efficiency have advanced our ability to
      manipulate materials with great precision on the micrometer and, more recently,
      on the nanometer scale. Certainly, the semiconductor and integrated circuit
      industry has put the pressure on scientist and engineers to develop better and
      faster nanofabrication techniques. Furthermore, our curiosity as to how life
      works, and how it can be improved from a medical perspective, stands to gain a
      great deal from advances in nanotechnology. Novel nanofabrication techniques are
      opening up the possibilities for mimicking the inherently nano-world of the cell,
      i.e., the nanotopographies of the extracellular matrix (ECM) and the
      nanochemistry presented on both the cell membrane and the ECM. In addition,
      biosensing applications that rely on fabrication of high-density, precision
      arrays, e.g., DNA or gene chips and protein arrays, will gain significantly in
      efficiency and, thus, in usefulness once it becomes possible to fabricate
      heterogeneous nanoarrays. Clearly, continued advances in nanotechnology are
      desired and required for advances in biotechnology. In this review, we describe
      the leading techniques for generating nanopatterns with biological function
      including parallel techniques such as extreme ultraviolet interference
      lithography (EUV-IL), soft-lithographic techniques (e.g., replica molding (RM)
      and microcontact printing (muCP)), nanoimprint lithography (NIL), nanosphere
      lithography (NSL) (e.g., colloid lithography or colloidal block-copolymer micelle
      lithography) and the nanostencil technique, in addition to direct-writing
      techniques including e-beam lithography (EBL), focused ion-beam lithography
      (FIBL) and dip-pen nanolithography (DPN). Details on how the patterns are
      generated, how biological function is imparted to the nanopatterns, and examples
      of how these surfaces can and are being used for biological applications will be
      presented. This review further illustrates the rapid pace by which advances are
      being made in the field of nanobiotechnology, owing to an increasing number of
      research endeavors, for an ever increasing number of applications.

PMID- 17037833
TI  - The analytical approach to polydimethylsiloxane microfluidic technology and its
      biological applications.
AB  - This review article discusses PDMS (polydimethylsiloxane) microfluidic devices
      and their biological applications. First, the already developed devices are
      classified from the viewpoints of underlying technology within a common logical
      framework comprising single-layer, multilayer, and integrated devices, as well as
      surface chemistry modifications of PDMS. Combinatorial techniques are applied to
      re-derive existing devices within this framework. Next, the relevant scales of
      both microfluidics and biology are compared, obtaining the promise and
      limitations of PDMS microfluidics. Finally, the body of work is reclassified in
      terms of addressed biological applications and compared to the standard methods
      in cellular and molecular biology, to offer insights for future devices and
      applications.

PMID- 17037834
TI  - Immobilization of biomaterials to nano-assembled films (self-assembled
      monolayers, Langmuir-Blodgett films, and layer-by-layer assemblies) and their
      related functions.
AB  - For utilization of highly sophisticated functions of biomaterials in nano-scale
      functional systems, immobilization of biomaterials on artificial devices such as
      electrodes via thin film technology is one of the most powerful strategies. In
      this review, we focus on three major organic ultrathin films, self-assembled
      monolayers (SAM), Langmuir-Blodgett (LB) films, and layer-by-layer (LBL)
      assemblies, and from the viewpoints of biomaterial immobilization, typical
      examples and recent progresses in these film technologies are described. The SAM
      method allows facile contact between biomaterials and man-made devices, and well
      used for bio-related sensors. In addition, recent micro-fabrication techniques
      such as micro-contact printing and dip-pen nanolithography were successfully
      applied to preparation of biomaterial patterning. A monolayer at the air-water
      interface, which is a unit structure of LB films, provides a unique environment
      for recognition of aqueous biomaterials. Recognition and immobilization of
      various biomaterials including nucleotides, nucleic acid bases, amino acids,
      sugars, and peptides were widely investigated. The LB film can be also used for
      immobilization of enzymes in an ultrathin film on an electrode, resulting in
      sensor application. The LBL assembling method is available for wide range of
      biomaterials and provides great freedom in designs of layered structures. These
      advantages are reflected in preparation of thin-film bio-reactors where multiple
      kinds of enzymes sequentially operate. LBL assemblies were also utilized for
      sensors and drug delivery systems. This kind of assembling structures can be
      prepared on micro-size particle and very useful for preparation of hollow
      capsules with biological functions.

PMID- 17037835
TI  - The use of magnetic nanoparticles in the development of new molecular detection
      systems.
AB  - Magnetic nanoparticles have been widely used in biomolecular separation and
      discrimination which coincidentally also represents the basis for most current
      day molecular diagnostic procedures. The specificity, affinity, and binding
      capacity of magnetic nanoparticles depends on their size, form, dispersion, and
      surface chemistry. In this review, we will briefly analyze how these factors
      affect biomolecular separations and focus on the use of magnetic nanoparticles in
      monitoring the microbial biodiversity in the environment. We found that magnetic
      nanoparticles are especially effective for biomolecular separations in
      environmental samples collected and preserved with fixatives. This feature,
      together with the high sample throughput capability and the generic low cost,
      makes magnetic nanoparticles particularly suitable for environmental microbial
      monitoring. Furthermore, key features that permit the optimization of magnetic
      nanoparticles-based separations and that can be useful in the development of new
      analytical procedures are also discussed.

PMID- 17037836
TI  - Force measurements between emulsion droplets-ssDNA conjugates: a new tool for
      medical diagnostics.
AB  - We describe here a new system involving direct force measurements between
      biomolecules that could be used in biomedical diagnostics. The method consists in
      the use of magnetic emulsion droplets bearing immobilized single stranded DNA
      fragments (ssDNA, Deoxyribo Nucleic Acid). The immobilized ssDNA fragments are
      able to recognize complementary DNA molecules via specific hydrogen binding
      (hybridization process). The ssDNA used in this study are 32 bases
      oligonucleotides functionalized at their 5' extremity with biotin and then
      immobilized onto the magnetic nanodroplets via interactions with streptavidin
      previously chemically grafted onto the nanomagnetic support. The aim of this work
      is to evaluate the possible detection of captured nucleic acid targets via single
      force measurements as an alternative to classical ELOSA (Enzyme Linked Oligo
      Sorbent Assay). The obtained results are discussed mainly in terms of
      electrostatic interactions.

PMID- 17037837
TI  - Self assembly of DNA nanoparticles with polycations for the delivery of genetic
      materials into cells.
AB  - Increasing attention has been paid to technology used for the delivery of genetic
      materials into cells for gene therapy and the generation of genetically
      engineered cells. So far, viral vectors have been mainly used because of their
      inherently high transfection efficiency of gene. However, there are some problems
      to be resolved for the clinical applications, such as the pathogenicity and
      immunogenicity of viral vectors themselves. Therefore, many research trials with
      non-viral vectors have been performed to enhance their efficiency to a level
      comparable to the viral vector. Two directions of these trials exist: Material
      improvement of non-viral vectors and their combination with various external
      physical stimuli. In this study gelatin was selected as a non-viral carrier for
      DNA. To give a positive charge to gelatin, different extents introduction of
      ethylenediamine (Ed), spermidine (Sd), and spermine (Sm) were reacted with
      gelatin in the presence of a water-soluble carbodiimide. When positively charged
      gelatin derivatives (Ed, Sd, and Sm) were mixed with negatively charged DNA, a
      self assembly of DNA nanoparticle (complex) was formed within few minutes through
      electrostatic interaction. Irrespective of the type of gelatin derivatives, the
      apparent molecular size of DNA was reduced by increasing the gelatin/DNA mixing
      ratio to attain a saturated value of about 150 nm. The condensed gelatin/DNA
      complexes showed the zeta potential of 10-15 mV. The amount of DNA internalized
      into the cells was significantly increased by the complexation with every gelatin
      derivative. The cells incubated with the gelatin/DNA complexes exhibited
      significantly stronger luciferase activities than naked plasmid DNA. This study
      clearly demonstrates and self-assembled DNA complexes has potential as a gene
      delivery vechile and are stable to transfer genetic materials to cells.

PMID- 17037838
TI  - From hollow shells to artificial cells: biointerface engineering on
      polyelectrolyte capsules.
AB  - Biomimetic composites can be fabricated by coating hollow polyelectrolyte
      capsules with biological interfaces such as a phospholipid membrane and proteins.
      Polyelectrolyte capsules have been templated applying the Layer-by-Layer
      technique of polyelectrolyte assembled on decomposable cores, which are destroyed
      after the assembly of the polyelectrolyte multilayer. Phospholipid vesicles of
      200-300 nm size are spreaded on the capsule wall forming a continuous lipid
      membrane. Further functionalisation of the outer capsule wall can be achieved
      with fused virions and recrystallised S-layers. Compartimentation of the capsule
      interior with lipid vesicles has been possible by using a solvent exchange
      method. The functionalisation of the outer capsule surface with biomolecules,
      together with the creation of internal compartments in the capsule, open new
      nanobiotechnological challenges towards the fabrication of artificial cells.

PMID- 17037839
TI  - Stable photoinduced charge separation in nanostructured films containing a
      1,4,5,8-naphthalenetetracarboxylic diimide and cytochrome c.
AB  - Photoinduced electron transfer between 1,4,5,8-naphthalenetetracarboxylic
      diimides (NDI) and the redox protein cytochrome c (cyt c) was studied in solution
      and in spin-coated thin films. The NDI derivatives employed in this study were
      N,N'-bis(butyl)-1,4,5,8-naphthalenetetracarboxylic diimide (BNDI) and N,N'-bis(2
      phosphonoethyl)-1,4,5,8-naphthalenetetracarboxylic diimide (PNDI). Irradiation of
      the NDI in solution with UV light (365 nm), in the presence of cyt c, resulted in
      the reduction of the heme iron from the Fe3+ to the Fe2+ state. When PNDI and cyt
      c were co-deposited by spin-coating on quartz, glass, and silicon substrates,
      photoactive films were obtained. Exposition of the films to a UV lamp or natural
      sun light resulted in photoreduction of the protein, generating a stable charge
      separated state. Thin films containing segregated layers of BNDI and cyt c were
      also prepared. Irradiation of these films, however, resulted in protein
      degradation. The results can be explained through the formation of imide
      radicals, which transfer an electron to cyt c in the co-deposited films. In the
      case of segregated films, protein photodegradation suggests the formation of
      singlet oxygen within the films.

PMID- 17037841
TI  - Investigation of sisal fibers by atomic force microscopy: morphological and
      adhesive characteristics.
AB  - Atomic force microscopy (AFM) was used to study the nanoscale surface chemistry
      and morphological changes caused by chemical treatment of sisal fibers. Scanning
      Electron Microscopy (SEM) micrographs indicated that sisal in natura (bundle of
      fibers) is formed by fibers with diameters of approximately 10 microm. AFM images
      showed that these fibers consist of microfibrils with diameters varying from 250
      to 600 nm, which are made up of nanofibrils of ca. 20 nm in diameter. The
      adhesion force (pull-off force) between the AFM tip and the fibers surface
      increased after benzylation, pointing to a decrease in the polar groups on the
      sisal fiber. The adhesion map measured over a scan range of 3 microm was
      heterogeneous in samples treated with 40% NaOH and the low adhesion sites
      disappeared after benzylation. Using an established mathematical model, it was
      possible to evaluate the increase in adhesion work and consequently in the
      interaction between the AFM tip and sisal fibers. These results indicated that
      AFM can detect heterogeneity in the wettability of sisal fibers with nanometer
      resolution and can be applied in the study of fiber-matrix adhesion in polymer
      composites.

PMID- 17037840
TI  - Galactose derivative immobilized glow discharge processed polyethersulfone
      membranes maintain the liver cell metabolic activity.
AB  - New strategies aimed to surface modification of polymeric membranes are crucial
      to optimise cell-biomaterial interactions in vivo and in vitro biohybrid systems.
      In this paper, we investigated the surface modification of Polyethersulfone (PES)
      membranes by plasma polymerisation of acrylic acid monomers (PES-pdAA) and by
      immobilization of galactonic acid through a hydrophilic "spacer arm" molecule
      (PES-pdAA-SA-GAL). The modification steps were characterised by high resolution X
      ray photoelectron spectroscopy. The performance of modified and unmodified
      membranes was evaluated by assessing the expression of liver specific
      biotransformation functions of pig and human hepatocytes. Human liver cells
      cultured on PES-pdAA-SA-GAL membranes displayed an enhanced albumin production,
      urea synthesis and protein secretion for 24 days of culture. The immobilisation
      of galactose derivative units on the membrane allowed specific interactions with
      hepatocytes biomimicking the cellular microenvironment and produced an
      improvement of the long-term maintenance and differentiation of human
      hepatocytes.

PMID- 17037842
TI  - Immobilization of methylene blue on self-assembled iodine monolayers on gold.
AB  - The immobilization of methylene blue (MB) on iodine-covered Au(111) is studied by
      electrochemical techniques, scanning tunneling microscopy (STM), Auger Electron
      Spectroscopy (AES), and Raman spectroscopy. Results show that MB species are
      efficiently adsorbed on the square root of 3 x square root of 3 R30 degrees I
      lattice on Au(111). The electrochemical behavior of the adsorbed MB molecules is
      reversible, indicating a relatively fast electron transfer from the Au(111)
      surface to the immobilized MB species through the iodine layer. STM images with
      molecular resolution are consistent with adsorption of MB dimers on a square root
      of 3 x square root of 3 R30 degrees I lattice placed atop of the Au(111)
      substrate. Results are compared to those obtained for MB immobilized on Au(111)
      covered by S(n) (n = 3-8) surface structures.

PMID- 17037843
TI  - Analysis of extracellular matrix production in artificial cartilage constructs by
      histology, immunocytochemistry, mass spectrometry, and NMR spectroscopy.
AB  - Artificial cartilage constructs based on primary porcine chondrocytes embedded in
      agarose gel were cultivated for six weeks under static, free swelling conditions.
      Standard biochemical assays, immunocytochemical staining methods, MALDI-TOF mass
      spectrometry, and non-invasive 13C solid-state NMR spectroscopy were used to
      assess cell proliferation, chondrocyte metabolism, extracellular matrix
      composition, matrix production, and the nanoarchitecture of the macromolecules in
      the constructs. In particular the production of sulphated glycosaminoglycans such
      as chondroitin sulphate was investigated quantitatively. Standard methods such as
      histological and immunocytochemical tools as well as spectrophotometric assays
      indicated the production of extracellular matrix in the artificial cartilage
      constructs. In addition, MALDI-TOF mass spectrometric data allowed to clearly
      identify the production of chondroitin sulphate in the tissue engineered
      cartilage. While all these methods require invasive sample treatment, 13C NMR
      spectroscopy allows to study the composition of the artificial cartilage
      constructs without previous manipulations. Though lower in sensitivity, 13C NMR
      spectra clearly showed the presence of chondroitin sulphate in the constructs. To
      increase the sensitivity of the NMR method, a culture medium that contained
      uniformly 13C labelled glucose but no sodium pyruvate or L-glutamine was used.
      Thus, further insights into the chondrocyte metabolism ex vivo are possible.
      Therefore, MALDI-TOF mass spectrometry and 13C solid-state NMR are useful
      experimental techniques that can assist the quantitative evaluation and quality
      control of artificially engineered tissues.

PMID- 17037844
TI  - Controlled DNA-templated metal deposition: towards ultra-thin nanowires.
AB  - In this paper, we report the metallization of a dsDNA template using a novel
      photography-derived two-step strategy in which dsDNA is first complexed with
      Ag(I) ions and then irradiated with UV light at 254 nm. The nucleobases act as
      light harvesters and sensitizers, triggering the photoreduction of the complexed
      silver ions. This process yields a silver nanoparticles blueprint along the DNA
      strand. The silver latent image is then developed by depositing metallic nickel
      through an electroless plating process. This photography-derived procedure
      generates very homogeneous and evenly distributed strings of silver-core/nickel
      shell nanoparticles. Although still discontinuous, we believe that such chains
      can serve as the base for obtaining continuous metal nanowires. Furthermore, this
      process can most likely be extended to other plating metals, resulting in a
      broadly general procedure for metallizing DNA with a variety of different
      materials. Because of the intrinsic simplicity in using light as the key step,
      this methodology might be amenable to large-scale development, eventually leading
      to a very efficient molecular-photolithography process.

PMID- 17037845
TI  - Entropic interactions in soft nanomaterials.
AB  - We review the forces that rule interactions between phospholipid membranes and
      other soft nanomaterials such as polymers and colloids. Contrary to traditional
      nanostructures, soft materials display a high susceptibility to the fluctuations
      of the thermal environment, leading to new forces of an essentially entropic
      nature.

PMID- 17037846
TI  - Development of an amperometric ethanol biosensor based on a multiwalled carbon
      nanotube-Nafion-alcohol dehydrogenase nanobiocomposite.
AB  - An amperometric biosensor for the determination of ethanol has been constructed.
      It comprises a multiwalled carbon nanotubes (MWNTs) conduit, a Nafion binder, and
      an alcohol dehydrogenase (ADH) function. The measurement of ethanol is based on
      the signal produced by beta-nicotinamide adenine dinucleotide (NADH), the product
      of the enzymatic reaction. The MWNTs are cylindrical with an outer diameter in
      the range 40-60 nm, an inner diameter in the range 2-5 nm, and a length of up to
      several micrometers. The homogeneity of the resulting nanobiocomposite film was
      characterized by field emission scanning electron microscopy (FESEM) and atomic
      force microscopy (AFM). The performance of the MWNTs-Nafion-ADH nanobiocomposite
      modified glassy carbon electrode was examined using cyclic voltammetry and
      amperometry in presence of NADH and in the presence of ethanol. The
      electrocatalytic activity of MWNTs towards the oxidation of NADH has allowed an
      effective low-potential amperometric determination of ethanol. In the case of 6
      mgmL(-1) ADH, the MWNTs-Nafion-ADH nanobiocomposite film displayed a sensitivity
      of 830 nAmM(-1), a linear range up to 0.1 mM, a detection limit of 3 microM, and
      a response time of about 4 s.

PMID- 17037847
TI  - Poly-lactide-co-glycolide microparticle sizes: a rational factorial design and
      surface response analysis.
AB  - Microsphere size is a primary determinant of solute release velocity. We present
      here a rational way for producing PLGA microspheres with different and controlled
      sizes. The following process variables were studied: Stirring velocity during the
      second emulsion step, dispersed and continuous phases volume ratio, and
      poly(vinyl alcohol) concentration in the continuous phase. A full factorial
      experimental design 2(3) with triplicate at the central point was used to
      determine the influence of variables on PLGA microsphere mean size. The stirring
      velocity and poly(vinyl alcohol) concentration were the main variables at 0.95
      significance level. An influence of PVA and stirring velocity on microspheres
      size is observed, there is no correlation for DP/CP volume ratio on size of
      microspheres. By combining the two variables--the stirring velocity and
      poly(vinyl alcohol) concentration, the surface response was analyzed. The
      increase of poly(vinyl alcohol) concentration with concomitant increase on
      stirring velocity produced microspheres with the lower sized. In contrast the
      lower poly(vinyl alcohol) concentration and the lower stirring velocity used
      produced the higher microspheres sized. Uniformly spherical and smooth
      microspheres (4-15 microm of diameter) were obtained. No significant difference
      was observed on Ponca S loading within the experimental region. Our results open
      the possibility of formulating PLGA microspheres with custom sizes performing a
      minimum of experiments as required for specific applications.

PMID- 17037848
TI  - Poly(amino acid)-facilitated electrochemical growth of metal nanoparticles.
AB  - Poly(amino acids) are natural chelating agents for various metal ions. Zinc ions
      were encapsulated in situ in a conductive polypyrrole film using polyglutamic
      acid as a localized complexing agent within the film. The subsequent
      electrochemical reduction of the metal ions to zero-valent metal leads to the
      formation of the nanoparticles. The electrochemical approach demonstrated in this
      report provides facile regeneration of the particles and also prevents
      aggregation of nanoparticles in the conductive polymeric film. The correlation of
      the amount of zinc with the thickness of the film indicates that the zinc resides
      largely in the outer layer of the film. TEM and EDS data show that the
      nanoparticles formed are composed of zinc and are 18 +/- 7 nm in diameter. The
      nanoparticle/ polymer composite was used to reduce halogenated organics,
      indicating its potential usefulness in remediation applications.

PMID- 17037849
TI  - Cell toxicity studies of albumin-based nanosized magnetic beads.
AB  - The aim of this study was to prepare bovine serum albumin-based beads containing
      maghemite nanoparticles incorporated via ionic magnetic fluid and to evaluate the
      cell toxicity of this biocompatible system using the J774-A1 cell line.
      Transmission electron micrographs obtained from the magnetic fluid sample were
      used to estimate the average particle diameter around 7.6 nm and diameter
      dispersion of 0.22. The BSA-based magnetic beads were prepared using the heat
      protein denaturation route. The nanoparticle concentration in the magnetic fluid
      sample used for the synthesis of the magnetic beads was in the range of 1.2 x
      10(16) to 2.3 x 10(17) particle/ml. The methodology used to investigate the cell
      toxicity of the magnetic beads was the classical MTT assay. Our observation
      showed that the toxicity against the J774-A1 cell line depends upon the amount of
      magnetic material incorporated into the magnetic nanobeads and was found to be
      14, 11, 9, 5, and 3% for 2.3 x 10(17), 1.2 x 10(17), 4.6 x 10(16), 2.3 x 10(16),
      and 1.2 x 10(16) particle/ml, respectively.

PMID- 17037850
TI  - The influence of urea on the structure of proteins in reversed micelles.
AB  - Static fluorescence measurements from the protein Tryptophan (Trp) residues and
      circular dichroism (CD) spectroscopy were used to investigate changes on the
      tertiary and secondary structures of the protein bovine serum albumin (BSA) and
      the dimeric enzyme hexokinase (HK) type PII from yeast, entrapped in reversed
      micelles (RMs). The latter were obtained from the amphiphilic AOT (sodium bis-2
      ethylhexyl sulfosuccinate) in n-hexane, at several water to surfactant ratios, W.
      BSA and HK were found to be anchored at the RM interface in close contact with
      the surfactant layer, regardless of the size of the waterpool. For BSA, such
      interaction promotes partial protein unfolding, according to CD data that showed
      a decrease in the content of helical structure from 66% in a buffer solution to
      48% in the micellar moiety. When urea was present in the micelle, further loss in
      helical structure occurred, thus indicating that the combined effect (micellar
      environment and urea) altered the BSA conformation to a greater extent than did
      RM or urea alone. Interestingly, Trps probed the same environment in the micelle,
      regardless of the presence of urea, but the fluorescence was quenched to a higher
      extent with urea. Thus, the fluorofore emission must have been affected either by
      the direct interaction of urea or by indirect exchange of water structure caused
      by urea interacting with water and the micellar interface. Both mechanisms might
      be of relevance in the solvation properties nearby the Trps. For HK, an
      association between the enzyme and the micelle interface was indicated in the CD
      spectra, which exhibited a randomized structure upon interaction, whatever the RM
      droplet size. The urea addition to the micelle water pool did not cause further
      impact on the HK conformation. In addition, the influence of urea at the RM
      interface was not sensed by the exposed tryptophans of the enzyme, unlike the
      results for BSA.

PMID- 17037851
TI  - Structural evaluation of phospholipidic nanovesicles containing small amounts of
      chitosan.
AB  - In this study we present a full characterization of nanovesicles containing
      soybean phosphatidylcholine and polysaccharide chitosan. The nanovesicles were
      prepared by the reverse phase evaporation method, including the preparation of
      reverse micelles followed by the formation of an organogel, which is dispersed in
      water to yield the final liposomal particles. Structural changes as a function of
      the chitosan amount and the filter porosity used in the nanovesicles preparation
      were studied employing Static and Dynamic Light Scattering as well as Small Angle
      X-ray Scattering. The hydrodynamic radius of the nanovesicles ranged between 106
      and 287 nm, depending on the chitosan contents and the filter porosity. A
      comparison with nanovesicles free of chitosan indicates the existence of higher
      contents of multilamellar structures that depends on the chitosan concentration
      in the vesicles containing chitosan. Typical spherical vesicles having nanometric
      diameters with polydispersity mostly desired in the biomedical area could only be
      achieved by filtration through a 0.45 microm porous filter.

PMID- 17037852
TI  - Zinc phthalocyanine/magnetic fluid complex: a promising dual nanostructured
      system for cancer treatment.
AB  - In this study we evaluated the photophysical, photochemical properties of the
      zinc phthalocyanine/ magnetic fluid (ZnPC/MF) complex in liposomal medium. As a
      result of the present investigation we propose the liposome-encapsulated ZnPC/MF
      complex as a very promising nanostructured device for cancer treatment. The
      spectroscopy characterization and the in vitro dark toxicity of both ZnPC and
      ZnPC/MF complex in Hank's and in liposomal medium are reported. Our findings
      revealed that the spectroscopic properties of the ZnPC associated or not with MF
      presented little differences and are very close to what one expects from an ideal
      photosensitizer compound. Indeed, the ZnPC/MF complex in liposomal medium
      presented lower dark toxicity compared to the ZnPC/MF complex in Hank's, strongly
      supporting the use of the former for cancer treatment.

PMID- 17037853
TI  - Wet powder processing of sol-gel derived mesoporous silica-hydroxyapatite hybrid
      powders.
AB  - This paper describes a method by which a porous silica coating layer can be
      obtained on different apatite particles through a simple sol-gel synthesis route.
      Sol-gel derived powders of hydroxyapatite (HAP) and beta tricalciumphosphate
      (beta-TCP) were coated with a mesoporous silica using C16TAB
      (hexadecyltrimethylammonium bromide) as a template in order to induce mesophase
      formation. Further calcination of the material removes the template from the
      mesophase and leaves a highly ordered hexagonal arranged mesoporous silica
      structure with a core of HAP/beta-TCP. The phase purity of the SiO2/apatite
      composites has been thoroughly investigated by the means of FT-IR, XRD, and solid
      state 31P MAS NMR. The phase purity of these materials is shown to be dependent
      on the solubility properties of the used apatites. The hybrid materials are
      suitable as a multifunctional biomaterial where osteoconductive properties can be
      combined with drug delivery.

PMID- 17037854
TI  - Charge patterns as templates for the assembly of layered biomolecular structures.
AB  - Electric fields are used to guide the assembly of biomolecules in predefined
      geometric patterns on solid substrates. Local surface charges serve as templates
      to selectively position proteins on thin-film polymeric electret layers, thereby
      creating a basis for site-directed layered assembly of biomolecular structures.
      Charge patterns are created using the lithographic capabilities of an atomic
      force microscope, namely by applying voltage pulses between a conductive tip and
      the sample. Samples consist of a poly(methyl methacrylate) layer on a p-doped
      silicon support. Subsequently, the sample is developed in a water-in-oil
      emulsion, consisting of a dispersed aqueous phase containing biotin-modified
      immunoglobulinG molecules, and a continuous nonpolar, insulating oil phase. The
      electrostatic fields cause a net force of (di)electrophoretic nature on the
      droplet, thereby guiding the proteins to the predefined locations. Due to the
      functionalization of the immunoglobulinG molecules with biotin-groups, these
      patterns can now be used to initiate the localized layer-by-layer assembly of
      biomolecules based on the avidin-biotin mechanism. By binding 40 nm sized biotin
      labelled beads to the predefined locations via a streptavidin linker, we verify
      the functionality of the previously deposited immunoglobulinG-biotin. All
      assembly steps following the initial deposition of the immunoglobulinG from
      emulsion can conveniently be conducted in aqueous solutions. Results show that
      pattern definition is maintained after immersion into aqueous solution.

PMID- 17037855
TI  - An engineered virus as a bright fluorescent tag and scaffold for cargo proteins-
      capture and transport by gliding microtubules.
AB  - We have demonstrated substantial capture and transport of fluorescently-labeled
      engineered cowpea mosaic virus (CPMV) using Drosophila kinesin-driven
      microtubules (MTs). The capture occurred through both NeutrAvidin (NA)-biotin and
      antibody (IgG)-antigen interactions. The MTs were derivatized with rabbit anti
      chicken IgG or biotin, and the virus was conjugated with chicken IgG or NA. The
      CPMV conjugate was introduced into standard MT motility assays via convective
      flow at concentrations as high as 1.36 nM, and became bound to the MTs in
      densities as high as one virus per microm of MT length. When the CPMV conjugate
      was present at 17 pM, the average speed of the MTs bearing the NA-virus was 0.59
      +/- 0.08 microm/sec, and that of those bearing IgG-virus was 0.52 +/- 0.15
      microm/sec. These speeds are comparable to those of the unladen MTs (0.61 +/-
      0.09 microm/sec), the presence of the virus on the MT causing only a small
      decrease in MT gliding speeds. The fluorescent CPMV appears to be superior to
      fluorescent polystyrene spheres of the same size, as both a reporter tag and a
      scaffold for MT-transported cargo proteins, because of its negligible non
      specific adsorption and superior brightness. This work is important for the
      development of sensors based on nanolocomotion and biological recognition, or new
      strategies for the nanoassembly of biological structures.

PMID- 17037856
TI  - Determination of the size of water-soluble nanoparticles and quantum dots by
      field-flow fractionation.
AB  - Field flow fractionation (FFF) technique is used to determine the size of water
      soluble Au, ZnS, ZnS-Mn2+ nanoparticles, and CdSe, CdSe-DNA quantum dots (QDs).
      The results of the FFF measurements are compared with the particle size analysis
      using conventional techniques like scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and dynamic light scattering (DLS)
      studies. Water-soluble gold nanoparticles (AuNPs) stabilized by mercaptosuccinic
      acid (MSA) as the ligand when analyzed by the SEM and DLS showed evidence of
      extensive aggregation, preventing an accurate determination of the average
      particle size. The TEM analyses without staining offered a facile measurement of
      the nanoparticle core but average particle size determination required analysis
      of the TEM image using image analysis software. On the other hand the FFF is
      seemingly a convenient and easy method for the determination of the average
      particle size of the AuNPs. In case of the ZnS and ZnS-Mn2+ nanoparticles with
      mercaptopropionic acid (MPA) as the capping agent severe aggregation prevented
      accurate estimation of particle sizes even by the high resolution TEM (HRTEM),
      where as the size determination by the FFF was very facile. Analysis of the CdSe
      DNA conjugate by the TEM was difficult as the sample got damaged upon exposure to
      the electron beam. The FFF cross-flow condition is apparently noninvasive and
      hence the technique was very effective in characterizing the CdSe-DNA QDs.
      Furthermore, using this simple technique it was possible to fractionate a sample
      of the AuNPs. The FFF measurement of water-soluble nanoparticles is an excellent
      complement to characterization of such particles by the conventional tools.

PMID- 17037857
TI  - Fabrication of nickel nanocontacts using nanostencils and electron beam assisted
      SiO2 deposition.
AB  - Nickel nanocontacts for studying ballistic magnetoresistance have been fabricated
      by sputtering through FIB prepared nanostencil masks and by using electron beam
      assisted deposition of SiO2 to reduce the size of FIB milled pores through
      silicon nitride membranes. These two methods are discussed in terms of the
      nanocontact sizes, fabrication, and yield. The smallest size of the nanocontacts
      prepared using the nanostencil method was 40 nm and by the filling method was 1-2
      nm. The maximum magnetoresistance measured was 1% and no evidence of a large
      ballistic magnetoresistance was observed.

PMID- 17037858
TI  - Measurement of light wavelength based on nanostructured ordered pore arrays.
AB  - A new method of light wavelength measurement is presented based on the
      nanostructured ordered pore arrays with multi-domains and centimeter square size
      formed by solution dipping-colloidal monolayer. Because of periodicity of the
      ordered pore arrays, perpendicular incidence of a parallel beam light on the
      array will lead to the diffraction spots or ring, depending on relative sizes of
      the beam and the domain in the arrays. The diffraction angle corresponds to
      wavelength of the incident light. On this basis, one can measure the wavelength
      of an incident light in transmission mode using such nanostructured ordered pore
      arrays, which is different from the conventional one fabricated from Michelson
      interference principle. Both the resolution and measurement precision can reach <
      1 nm in such a simple method. Comparatively, this new measurement setup is simple
      in structure, low in cost, convenient in measurement, and especially, small in
      size. It could be used for online demarcation and real-time measurement of light
      wavelength in such as, mine operation, seabed exploration, and even space
      exploration due to its miniature.

PMID- 17037859
TI  - Polymer-coated magnetic nanoparticles: surface modification and end
      functionalization.
AB  - ATRP (atom transfer radical polymerization) approach was employed to synthesis
      polymer-coated magnetite nanoparticles. These particles had an average diameter
      of 7.1 nm and a narrow size distribution. Characterization was performed using
      various techniques like Transmission Electron Microscopy (TEM), Ultraviolet
      Visible spectroscopy (UV-vis), Fourier Transform Infrared spectroscopy (FTIR),
      Atomic Force Microscopy (AFM), and Vibrating Sample Magnetometry (VSM). The
      challenge was to obtain a thin shell and discrete particles in an unagglomerated
      state. Several factors like presence/choice of solvent, monomer-to-initiator
      concentration and structure of initiator were found to play a key role in this
      study. Attempts have been made to tailor the polymer shells by end
      functionalization. This work has an enormous biomedical application potential.

PMID- 17037860
TI  - Preparation of Mg-vermiculite nanoparticles using potassium persulfate treatment.
AB  - Delamination/exfoliation process of the Mg-vermiculite (Letovice, Czech
      Republic), particles with size less than 5 microm, was studied after potassium
      persulfate treatment and compared with known method utilized hydrogen peroxide
      treatment. X-ray powder diffraction (XRPD) patterns showed that treatment of Mg
      vermiculite with different molar concentration of potassium persulfate: c = 0.02,
      0.04, and 0.08 mol x dm(-3) at the temperature 60 degrees C for 2 hr caused
      reduction of relative intensity (I(rel.)) of the basal 001 diffraction to the
      15%, 9%, and 4%, respectively, compared to intensity of 001 diffraction of
      untreated Mg-vermiculite (I(rel.) = 100%). On the other hand I(rel.) of the 001
      diffraction of Mg-vermiculite after treatment with 30% and 50% (c = 9.8 and 17.4
      mol x dm(-3)) hydrogen peroxide at the 60 degrees C for 2 hr decreased only to
      I(rel.) = 36% and 32%, respectively. Atomic Force Microscopy (AFM) and Scanning
      Electron Microscopy (SEM) verified effect of potassium persulfate treatment on
      structure degradation which is connected with higher degree of
      delamination/exfoliation of the particles and their cracking into nano-sized
      particles.

PMID- 17037861
TI  - Mechanical property of lipid-coated polyelectrolyte microcapsules.
AB  - The deformations of lipid coated polyelectrolyte capsules induced by osmotic
      pressure were determined in poly(styrene sulfonate, sodium salt) (PSS) solution
      by making use of the fact that PSS molecules with a molecular weight 70000 will
      not penetrate into the capsules. At a critical osmotic pressure the initial
      spherical capsules changed their shape and became an invagination. The
      measurements of single particle light scattering provided the wall thickness of
      the lipid-coated capsules with 25.6 nm while the thickness for pure
      polyelectrolyte capsules in solution is about 21.6 nm, indicating that the
      coating lipid layer has about 4 nm thickness. It demonstrates that DMPA forms a
      bilayer on the surface of polyelectrolyte capsules. With these data, that the
      elasticity coefficient of the lipid-coated capsules is about 426 Mpa can be
      obtained.

PMID- 17037862
TI  - Self-organized monolayer formation from binary mixtures of substituted alkyl
      chains studied by STM.
AB  - The molecular assembly of p-iodo-phenyl octadecyl ether (I-POE), p-iodo-phenyl
      docosyl ether (I-PDE) and a binary mixture of these two molecules on graphite has
      been studied using a scanning tunneling microscope. Each molecular system self
      assembles on the graphite surface to form a stable monolayer. For the binary
      system, the I-POE and I-PDE molecules do not mix on the surface, preferring
      instead to form isolated monolayer domains. Here, the I-POE molecules are
      preferentially adsorbed on the graphite surface, due to the effects of alkyl
      chain length and the functional group on the monolayer structure.

PMID- 17037863
TI  - Visible light active photocatalytic degradation of bisphenol-A using nitrogen
      doped TiO2.
AB  - Nitrogen doped titania was prepared by low temperature sol-gel method using
      titanium precursor and nitrogen containing bases like triethylamine and
      tetramethyl ammonium hydroxide compounds. The materials were characterized by
      XRD, BET, SEM, XPS, DRS-UV, and FT-IR techniques. DRS-UV study substantially
      indicates shift of the absorption edge of TiO2 to lower energy region. The phase
      composition, crystallinity, specific surface area, and visible light activity of
      nitrogen doped titania depend upon the preparation conditions. Photocatalytic
      degradation of bisphenol-A in aqueous medium was investigated by TiO2 and
      nitrogen doped TiO2 under visible light irradiation in a batch photocatalytic
      reactor. The results indicate higher visible light activity for nitrogen doped
      TiO2 than commercial TiO2 (Degussa P25) for bisphenol-A degradation. The
      influence of various parameters such as initial concentration of bisphenol-A,
      catalyst loading and pH was examined for maximum degradation efficiency.

PMID- 17037864
TI  - Chitosan-mediated synthesis of gold nanoparticles by UV photoactivation and their
      characterization.
AB  - Recent researches have largely been focused on chitosan, which is deacetylated
      chitin, the most abundant natural polysaccharide after cellulose. In this paper,
      we report the fabrication of gold nanoparticles (GNPs) by UV photoactivation in
      the presence of biopolymeric chitosan and the tracing of the gold salt solution
      aging. Detailed UV-visible spectroscopy study witnessed the evolution of the
      surface plasmon resonance (SPR) adsorption during the GNP growth. The effect of
      chitosan in aqueous solution for the GNP preparation was investigated in detail.
      The results indicated the size and distribution of GNPs could be controlled over
      by altering the concentration of chitosan, and the GNP growth during aging was a
      chitosan-mediated autocatalytic process. Fourier transform infrared spectroscopy
      (FTIR) showed the hydroxyl in molecular chitosan was oxidized to carbonyl groups
      in the fabrication of GNPs after aging and nitrogen atoms are the main sites for
      the complexation of chitosan with Au atoms. Our synthesis method in the present
      way can be used to form self-assemble monolayers of GNPs and fabricate biosensors
      based on surface plasmon resonance effect.

PMID- 17037865
TI  - Synthesis of neodymium hydroxide nanotubes and nanorods by soft chemical process.
AB  - A facile soft chemical approach using cetyltrimethylammonium bromide (CTAB) as
      template is successfully designed for synthesis of neodymium hydroxide nanotubes.
      These nanotubes have an average outer diameter around 20 nm, inner diameter
      around 2 nm, and length ranging from 100 to 120 nm, high BET surface area of
      495.71 m(2) g(-1). We also find that neodymium hydroxide nanorods would be
      obtained when CTAB absented in reaction system. The Nd(OH)3 nanorods might act as
      precursors that are converted into Nd2O3 nanorods through dehydration at 550
      degrees C. The nanorods could exhibit upconversion emission characteristic under
      excitation of 591 nm at room temperature.

PMID- 17037866
TI  - Dispersion of single-walled carbon nanotubes in a non-polar polymer, poly(4
      methyl-1-pentene).
AB  - Poly(4-methyl-1-pentene), PMP, a high melting polymer composed of hydrogen and
      carbon, has the potential to become an alternative to polyethylene (PE) as
      shielding material against Galactic Cosmic Radiation (GCR). PMP exhibits higher
      thermal stability than PE and is transparent in the UV/visible region of the
      electromagnetic spectrum. Single walled carbon nanotubes (SWNTs) were pretreated
      with a polar solvent, N, N-Dimethylformimide (DMF), and then dispersed in a
      halogenated hydrocarbon, cyclohexyl chloride, which also dissolved the non polar
      polymer, PMP. The composites were characterized via differential scanning
      calorimetry (DSC), dynamic mechanical analysis (DMA), microhardness measurements,
      and optical microscopy. DMA data revealed that the carbon nanotubes contributed
      to the enhancement of the high temperature alpha(c) relaxation which is thought
      to arise from motion around crystalline regions in the matrix. The storage
      modulus (60 Hz) increased from 2409 MPa in the neat PMP to 3716 MPa at -50
      degrees C. The magnitude of the increase diminished near and above the glass
      transition region; the glassy matrix restricted motion of the crystalline
      regions. DSC data showed an increase in the percent crystallinity of the
      composite (75%) as compared to the neat polymer (68%). Low concentrations of
      nanotubes, when well dispersed, produced nanocomposites with varying degrees of
      transparency.

PMID- 17037867
TI  - Combustion oxidization synthesis of unique cage-like nanotetrapod ZnO and its
      optical property.
AB  - Cage-like nano-tetrapod ZnO is a novel structure, which was successfully
      synthesized by combustion oxidation at 850 degrees C. No catalyst or carrier
      gases were used. Thorough SEM and TEM analyses revealed that the linking legs of
      the tetrapod ZnO can have or not interface. The formation or not of an interface
      is discussed and it was attributed to different growth process of the cage-like
      ZnO nano-tetrapod. Enhanced UV emission peak at the wavelength of 375 nm,
      featuring high intensity and narrow width, indicates a highly crystalline
      structure. A green emission, recorded at 502 nm, was related to the defects of
      the surface of the branching configuration as well as to the ZnO nuclei of the
      cage-like nano-tetrapod ZnO.

PMID- 17037868
TI  - Strong green luminescence of Mg-doped ZnO nanowires.
AB  - The ZnO nanowires doped with Mg (Mg-ZnONWs) were produced by thermally oxidizing
      Zn and Mg powders. TEM and XRD patterns indicated that Mg-ZnONWs were crystalline
      with a wurzite structure. The Mg doping was confirmed with XPS measurements. The
      green emission band at 500 nm in the photoluminescence spectrum of Mg-ZnONWs and
      peaks at 366 nm in low intensity were observable. Raman spectrum indicated that
      oxygen deficiency was not the dominant factor for the green emission. The green
      emission was further directly observed with a digital camera.

PMID- 17037869
TI  - Orthogonally-oriented nanotube arrays: theory.
AB  - A novel surface involving ordered arrays of partially-embedded carbon nanotubes
      is developed theoretically. Analysis indicates it should exhibit ultra-low values
      for friction, adhesion and wear, and also possess superior thermal and electrical
      properties. The surface consists of orthogonally-oriented, self-assembling arrays
      of carbon nanotubes, partially embedded lengthwise in a solid substrate.
      Calculations indicate that stiction forces due to van der Waals interactions can
      be made small, perhaps more than an order of magnitude less than for Teflon and
      other advanced perfluorocarbons. Static and kinetic frictional forces could be
      three orders of magnitude less than for conventional solids.

PMID- 17037870
TI  - Possible binding sites for biotin stabilized water soluble Ag nanoparticles: an
      experimental and theoretical study.
AB  - The evolution of Ag nanoparticles by photochemical reduction method and the
      effect of biotin on their UV-Visible absorption spectrum were studied. Surface
      modification studies were carried out on chemically reduced Ag nanoparticles. ATR
      FTIR studies showed that the biotin molecules bind with the surface of Ag
      nanoparticles through the oxygen of the carboxylate group. Theoretical
      calculations were carried out on the structure of the biotin and the silver
      complex of biotin (biotin(-)-Ag+) by optimizing their structures using density
      functional calculations with the B3LYP method using the LANL2DZ basis set.
      Theoretical calculations and experimental evidence favors a preferential binding
      of biotin molecule to Ag nanoparticles through the carboxylate group.

PMID- 17037871
TI  - Synthesis of nanocrystalline tin oxide thin film by swift heavy ion irradiation.
AB  - Nanocrystals of tin oxide were formed in e-beam evaporated films by swift heavy
      ion (SHI) irradiation. The nucleation of nanocrystals occurred due to electronic
      excitation by swift heavy ion. Nanophase thin films are characterized
      systematically by HRTEM, GAXRD, EDX, and UV/NIS absorption techniques.
      Nanocrystals having size of 8 nm radius are synthesized in different substrates
      during swift heavy ion irradiation and without subsequent annealing. SHI induced
      nanocrystallization could be achieved in both crystalline and non-crystalline
      substrates.

PMID- 17037872
TI  - Triphenyl benzene-bridged fluorescent silsesquioxane: shape-controlled hybrid
      silicas by hydrolytic conditions.
AB  - A new silsesquioxane molecule was synthesized, in which triphenyl benzene was
      connected with three Si(OC2H5)3 groups using three urea groups as the bridge. The
      molecule could self-assemble through the intermolecular H-bonding among urea
      groups and pi-pi interaction of triphenyl benzene core in the solution and it
      could also be transferred into hybrid silicas by hydrolysis. When the non
      preorganized silsesquioxane was hydrolyzed, isolated spherical hybrid silica was
      gained. However, when the silsesquioxane was preorganized before the
      hydrolyzation uniform interconnected spherical hybrid silica and intertwined
      nanofibrous one could be generated under acidic and basic conditions,
      respectively. The photoluminescence (PL) spectra of the obtained hybrid silicas
      showed that they still kept the emission properties of their precursor
      silsesquioxane, and the shift of the emission bands was due to the pi-pi
      interaction of triphenyl benzene in the course of polycondensation.

PMID- 17037873
TI  - Bicrystalline zinc oxide nanocombs.
AB  - Bicrystalline ZnO nanocombs have been prepared by zinc powder evaporation at 650
      degrees C. Structural analysis showed that as-synthesized samples are composed of
      two crystals that form a twin structure parallel to the (113) plane with the
      growth direction of the branching nanowires and the main stem closely parallel to
      (0001) and (0110), respectively. Due to the unique twin structures, both sides of
      the main stems could be Zn-terminated ZnO(0001) polar surfaces. The chemically
      active surfaces make the aligned branching nanowires grow from both sides of the
      main stems, which is consistent with the structure of the obtained bicrystalline
      nanomaterials. The growth of bicrystalline ZnO nanocombs can be explained by
      polar-surface dominated growth and twins induced growth mechanisms.

PMID- 17037874
TI  - Preparation of conductive polypyrrole-palladium composite nanospheres by inverse
      microemulsion polymerization.
AB  - Conductive polypyrrole-palladium (PPy-Pd) composite nanospheres of about 50 nm in
      diameter, containing dispersed Pd metal nanoparticles of about 2-4 nm in size,
      were prepared in a 1-step oxidative polymerization of pyrrole by Pd(NO3)2.
      Pyrrole was oxidized by Pd(NO3)2 in an inverse microemulsion polymerization
      system, yielding PPy nanospheres and elemental Pd nanoparticles simultaneously.
      Palladium nanoparticles were uniformly dispersed in the nanospheres of PPy
      chains. The latter also exhibited an enhanced effective conjugation. The chemical
      composition of the PPy-Pd composite nanospheres was characterized by X-ray
      photoelectron spectroscopy and FTIR spectroscopy. The crystalline structure of
      the Pd nanoparticles was deduced from X-ray diffraction patterns. The morphology
      of the composites was revealed by scanning and transmission electron microscopy.

PMID- 17037875
TI  - Influence of anions on the morphology of nanophase alpha-MnO2 crystal via
      hydrothermal process.
AB  - The alpha-MnO2 nanocrystal nanowires, nanoplates, and nanoflowers have been
      successfully synthesized by a common hydrothermal treatment of different
      solutions containing KMnO4 and NH4X (X = Cl-, Ac-, NO3-, SO4(2-), and PO4(3-)) at
      140 degrees C for 24 h. The influence of anions on the morphology of final
      product is discussed. According to our experimental results, we proposed a
      possible mechanism of the formation of different morphologies of nano-phase alpha
      MnO2 and considered that the growing process was due to the initial plate-like
      MO(x) absorbing different anions and cooperation with them, which contributes to
      the final morphology of the product.

PMID- 17037876
TI  - Large-scale synthesis of a novel tri(8-hydroxyquioline) aluminum nanostructure.
AB  - A novel tri(8-hydroxyquioline) aluminum (AlQ3) nanostructure was prepared on
      large scale at low cost by low-temperature physical vapor deposition (PVD). The
      morphologies, the chemical bondings, and photoluminescence of the AlQ3
      nanostructure were investigated by environmental scanning electronic microscopy
      (ESEM), Fourier transform infrared spectrum (FT-IR), and photoluminescence (PL)
      spectra, respectively. The AlQ3 nanostructure was composed of micro-sphere with
      nanowire-cluster growing on the surface. The diameter of micro-sphere and
      nanowire were about 5 microm and 80 nm, respectively. FT-IR results indicated
      that the AlQ3 molecule had a strong thermal stability under research conditions.
      The growth mechanism of the novel nanostructure was discussed. The novel organic
      nanostructure would be believed to attractive building field-emission devices and
      other optical devices.

PMID- 17037877
TI  - Sonochemical synthesis of CdS and CdSe nanowires.
AB  - A convenient sonochemical route was developed to fabricate one-dimensional (1D)
      CdS or CdSe assemblies via a simple template method with two-steps: Firstly, the
      colloid one dimensional cadmium hydroxide particles were prepared as templates
      under sonication; then, the colloid particles were converted into 1D CdS or CdSe
      assemblies via a replacement reaction after the surface nucleation and crystal
      growth processes. The as-prepared CdS and CdSe nanowires were characterized by
      XRD, TEM, XPS, and UV-visible Spectroscopy. The effects of the ultrasonic
      irradiation were discussed. It is believed that the ultrasound irradiation played
      a positive role in both the assembly of the colloid cadmium hydroxide particles
      into the 1D structure and the growth of CdSe and CdS nanowires. The effects of pH
      on the morphologies of the cadmium hydroxide template were also discussed. The
      band gaps of the as-prepared 1D CdSe and CdS assemblies were calculated to be 3.1
      eV and 4.9 eV, respectively, indicating the quantum size effect. The as-prepared
      products might have potential applications in nanodevices in future.

PMID- 17037878
TI  - Synthesis of core-shell Au@polypyrrole nanocomposite using a dendrimer-template
      approach.
AB  - Conducting polymeric nanostructures have been reported recently, which were
      produced from polypyrrole (PPy), including hollow nanocapsules, nanofibers,
      nanoporous membranes, nanowires, and nanofilms. In most cases, new synthetic
      routes were used aimed at controlling specific properties of these conducting
      nanostructures at the molecular level. In this communication we present a new
      chemical route to synthesize polypyrrole-based nanocomposites, in which
      polyamidoamine (PAMAM) dendrimers encapsulating Au nanoparticles are used as
      template. The two-step synthesis comprises the reduction of Au nanoparticles
      inside PAMAM molecules followed by PPy polymerization around the PAMAM-Au
      nanoparticles. The structure of the core-shell PAMAM-gold@polypyrrole nanospheres
      comprises a 40 nm PPy shell enclosing a core of 3 nm gold nanoparticles, as
      revealed by Transmission Electronic Microscopy (TEM). This new, environmentally
      friendly approach may be suitable to produce hybrid nanomaterials for
      applications in catalysis, batteries, sensors, and micro/nanoelectronic devices.

PMID- 17037879
TI  - Scepticism greets plans to take politics out of the NHS.

PMID- 17037880
TI  - At risk: the safety agency that failed to set the world on fire.

PMID- 17037881
TI  - On voting for your healthcare.

PMID- 17037882
TI  - Data briefing. Deficit forecasts, financial reality.

PMID- 17037883
TI  - Mental health: same difference.
AB  - There is widespread ignorance over services provided by the private and voluntary
      sector. These can be cheaper and more flexible, and coming from niche market
      tends to make them competitive. Opportunities for joint ventures with the NHS
      appear more timely than ever and highlight the trend towards community-based
      care, cohesion and co-operation.

PMID- 17037884
TI  - On mental health.

PMID- 17037885
TI  - The education and the digital revolution continues.

PMID- 17037886
TI  - Dentinal hypersensitivity: a review.
AB  - Tooth sensitivity is a very common clinical presentation which can cause
      considerable concern for patients. This condition is frequently encountered by
      periodontists, dentists, hygienists and dental therapists. The management of this
      condition requires a good understanding of the complexity of the problem, as well
      as the variety of treatments available. This review considers the aetiology,
      incidence and management of dentinal hypersensitivity.

PMID- 17037887
TI  - Prevalence and side preference for tooth grinding in twins.
AB  - BACKGROUND: Estimates of the prevalence of tooth grinding in children range
      considerably, reflecting different methods of recording. The main aims of this
      study were to determine the prevalence of tooth grinding in monozygotic (MZ) and
      dizygotic (DZ) twin pairs by assessing wear faceting on the primary canines, and
      to compare the faceting on the right and left to determine whether children have
      a side preference for grinding. METHODS: The sample consisted of 116 MZ twin
      pairs and 124 dizygous DZ twin pairs, all participants in an ongoing study of
      dento-facial development at the dental schools in Adelaide and Melbourne.
      Evidence of wear faceting on primary maxillary and mandibular canine tips was
      recorded from dental casts, and the side with the larger wear facet recorded.
      Types of occlusal relationship, handedness, zygosity and gender were also
      recorded, and associations between variables analysed statistically. RESULTS:
      Canine tip wear facets were found in 100 per cent of the sample, and grinding was
      lateralized in 59 per cent of children. MZ twin pairs showed a higher discordance
      for grinding side preference than DZ twin pairs (33.8 per cent compared with 16.8
      per cent), providing evidence of a mirror-imaging effect for grinding side
      preference. There was no strong evidence that individuals had the same preference
      for grinding side and handedness, although right-handers (RH) showed a preference
      for a grinding side more often than non-right-handers (NRH) (63.6 per cent
      compared with 51.2 per cent), consistent with previous findings that RHs display
      more cerebral lateralization than NRHs. CONCLUSIONS: Tooth grinding appears to be
      a universal phenomenon in children and is commonly expressed more on one side
      than the other. The significantly higher discordance for grinding side preference
      in MZ twin pairs compared with DZ twin pairs may reflect a mirror-imaging effect
      in the former. However, at present we have no evidence to suggest that handedness
      and preferred tooth grinding side are associated.

PMID- 17037888
TI  - Maxillofacial trauma in major trauma patients.
AB  - BACKGROUND: Trauma has been identified as a major public health problem in
      Australia. Maxillofacial trauma constitutes a significant proportion of trauma,
      although epidemiological studies in Australia are few. The purpose of this study
      was to assess the prevalence and the epidemiological pattern of maxillofacial
      trauma occurring in major trauma patients. METHODS: Data were obtained from the
      Victorian State Trauma Registry, which included all major trauma patients in
      Victoria. All data relating to maxillofacial trauma defined according to
      Abbreviated Injury Scale and International Classification of Diseases codes from
      1 July 2001 to 30 June 2004 were selected. Data collected included demographic
      and injury details, and operative procedures carried out. RESULTS: Sixteen per
      cent of major trauma patients sustained maxillofacial trauma. The highest
      frequency of injuries occurred in the 15-24 years age group. More males were
      affected than females (3:1). The majority of injuries were due to
      transportrelated causes (69 per cent) and occurred mostly on roads, streets or
      highways (70 per cent). Falls were the cause of 15 per cent of injuries, 10.5 per
      cent of these injuries were fatal while 20.7 per cent needed rehabilitation. The
      most common type of bony injury was a fractured maxilla. CONCLUSION: The need for
      preventive strategies to be reinforced has been highlighted as transport-related
      injuries remain high especially in the younger age groups.

PMID- 17037889
TI  - Hospitalization of Western Australian children for oral health related
      conditions: a 5-8 year follow-up.
AB  - BACKGROUND: This study investigated in-patient oral health care provision for
      children under 18 years of age in Western Australia. METHODS: Hospitalizations of
      children for oral health conditions over a four-year period were analysed using
      data obtained from the Western Australian Hospital Morbidity Data System (HMDS).
      This study followed a previously published study examining similar data for 1995.
      RESULTS: Between 1999-2000 and 2002-2003, a total of 26 497 episodes of care were
      attributed to oral health conditions among children aged 0-17 years. The cost of
      this care exceeded $40 million. Embedded and impacted teeth accounted for 33.2
      per cent of oral health episodes, dental caries 28.3 per cent, pulp and
      periapical tissue conditions 7.1 per cent and dentofacial anomalies 6.1 per cent.
      With the exception of the infant age group (0-1 years), non-Aboriginal children
      had higher admission rates than Aboriginal children. In the 13-17 year age group
      a non-Aboriginal child was 31 times more likely to be admitted to hospital for an
      oral condition than an Aboriginal child. CONCLUSIONS: This study confirms the
      impact of oral health related conditions among children in Western Australia. It
      is also clear that there are differences between age and population groups in
      terms of access to in-patient dental services and exposure to risk factors for
      specific oral conditions.

PMID- 17037891
TI  - Fluoride content of still bottled water in Australia.
AB  - BACKGROUND: Recently there has been a considerable increase in the consumption of
      bottled water in Australia. Overseas studies have found the fluoride levels in
      many bottled waters are well below levels considered optimal for preventing
      dental caries. This raises the concern that if bottled water is regularly
      consumed an effective means of preventing dental caries is unavailable. The aim
      of this study was to determine the fluoride concentration in 10 popular brands of
      still bottled water currently sold in Australia. METHODS: The fluoride content of
      water samples were determined using an ion analyser and compared to a fluoride
      standard. RESULTS: The fluoride concentration of all bottled waters was less than
      0.08 ppm. Only three of the 10 brands indicated the fluoride content on their
      labels. Melbourne reticulated water was found to be fluoridated at 1.02 ppm.
      CONCLUSIONS: All bottled waters tested contained negligible fluoride which
      justifies the concern that regular consumption of bottled water may reduce the
      benefits gained from water fluoridation. It is recommended that all bottled water
      companies should consider stating their fluoride content on their labels. This
      will inform consumers and dental care providers of the levels of fluoride in
      bottled water and allow an informed decision regarding consumption of fluoridated
      versus non-fluoridated drinking water.

PMID- 17037890
TI  - Ion uptake into demineralized dentine from glass ionomer cement following
      pretreatment with silver fluoride and potassium iodide.
AB  - BACKGROUND: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been
      shown to provide a pronounced antimicrobial action against caries. The clinical
      application of this material has been limited by the staining associated with
      both teeth and tooth coloured restorative materials. The application of potassium
      iodide (KI) after AgF eliminates stain formation. The purpose of this study was
      to determine if a prior application of silver fluoride and potassium iodine to
      demineralized dentine affected the uptake of strontium and fluoride from a glass
      ionomer cement restoration. METHOD: Three cavities were prepared in each of five
      recently extracted human third molars. The cavities were demineralized and
      treated as follows. In each tooth, one cavity was left as a control, one cavity
      was restored with glass ionomer cement and one cavity was treated with 1.8M AgF
      and a saturated KI solution and then restored with glass ionomer cement. The
      penetration of the various elements into demineralized dentine was measured by
      their relative percentage weights using electron probe microanalysis (EPMA).
      RESULTS: Fluoride uptake was significantly higher in the AgF and KI treated
      samples compared to the other two samples and significantly higher in the glass
      ionomer restored sample compared to the control. The application of AgF and KI
      did not significantly interfere with the transfer of strontium from glass ionomer
      cement into dentine. Silver and iodine deposits were present in the demineralized
      dentine treated with AgF and KI. CONCLUSIONS: The application of AgF and KI onto
      dentine prior to the placement of glass ionomer cement did not significantly
      affect the strontium uptake into the subjacent demineralized dentine and the
      fluoride levels in this zone were significantly increased.

PMID- 17037892
TI  - Dissolution of porcine incisor pulps in sodium hypochlorite solutions of varying
      compositions and concentrations.
AB  - BACKGROUND: The solubility of dental pulp tissue in sodium hypochlorite has been
      extensively investigated but results have been inconsistent; due most likely to
      variations in experimental design, the volume and/or rate of replenishment of the
      solutions used and the nature of the tissues assessed. Traditionally, the sodium
      hypochlorite solutions used for endodontic irrigation in Australia have been
      either Milton or commercial bleach, with Milton being the most common. Recently,
      a range of Therapeutic Goods Administration (TGA) approved proprietary sodium
      hypochlorite solutions, which contain surfactant, has become available. Some
      domestic chlorine bleaches now also contain surfactants. The purpose of this
      study was to perform new solubility assessments, comparing Milton with new TGA
      approved products, Hypochlor 1% and Hypochlor 4% forte, and with a domestic
      bleach containing surfactant (White King). METHODS: Ten randomly assigned pulp
      samples of porcine dental pulp of approximately equal dimensions were immersed in
      the above solutions, as well as representative concentrations of sodium
      hydroxide. Time to complete dissolution was measured and assessed statistically.
      RESULTS: White King 4% showed the shortest dissolution time, closely followed by
      Hypochlor 4% forte. White King 1% and Hypochlor 1% each took around three times
      as long to completely dissolve the samples of pulp as their respective 4%
      concentrations, while Milton took nearly 10 times as long. The sodium hydroxide
      solutions showed no noticeable dissolution of the pulp samples. CONCLUSIONS: The
      composition and content of sodium hypochlorite solutions had a profound effect on
      the ability of these solutions to dissolve pulp tissue in vitro. Greater
      concentrations provided more rapid dissolution of tissue. One per cent solutions
      with added surfactant and which contained higher concentrations of sodium
      hydroxide were significantly more effective in dissolution of pulp tissue than
      Milton.

PMID- 17037893
TI  - Comparison of microshear bond strengths of four self-etching bonding systems to
      enamel using two test methods.
AB  - BACKGROUND: Recent advances in enamel and dentine adhesive technology have
      resulted in the emergence of many new adhesive systems. Self-etching bonding
      systems do not require a separate etching step and the newest systems are the
      "all-in-one" systems which combine etching, priming and bonding into a single
      application. This study reports laboratory enamel microshear bond strengths of a
      self-etching priming and three all-in-one systems and also evaluates two
      different microshear bond test methods. METHODS: One hundred and nineteen enamel
      specimens were bonded (0.8 mm diameter) with either Clearfil Protect Bond
      (Kuraray), Xeno III (Dentsply), G Bond (GC) or One-Up Bond F (Tokuyama) using
      Palfique Estelite resin composite and stored in 37 degrees Celsius water for
      seven days. The microshear bond test method used either a blade or wire to apply
      the shear stress. Results were analysed with one-way ANOVA and post hoc (Tukey)
      multiple comparison analysis. RESULTS: Clearfil Protect Bond demonstrated higher
      and more consistent bond strengths than Xeno III, G Bond or One-Up Bond F. The
      wire method showed much greater reliability in results, with a coefficient of
      variation half that of the blade method. CONCLUSIONS: All-in-one adhesives seem
      to be less reliable than the two-step self-etching priming adhesive when bonding
      to enamel. Test method can significantly affect results in the microshear bond
      test method.

PMID- 17037894
TI  - Ex vivo evaluation of the ability of four different electronic apex locators to
      determine the working length in teeth with various foramen diameters.
AB  - BACKGROUND: The aim of this ex vivo study was to evaluate the accuracy of four
      electronic apex locators (EALs) to determine the working length in teeth with
      various foramen diameters. Our previous study revealed that electronically
      measured canal length was influenced by the root canal diameter. It is not known
      whether foramen size would interfere with the reading accuracy of an EAL.
      METHODS: A total of 36 extracted human lower single rooted premolar teeth were
      divided into four groups of nine teeth each. In groups A, B and C, the root
      canals were instrumented using #10-80, #10-100 and #10-120 K-files, and the tip
      of size #80, #100 and #120 K-files were permitted to pass through the apical
      foramen to a length of 1mm, respectively. In group D, the teeth were instrumented
      using #10-140 K-files and the tip of #140 K-file was permitted to pass through
      the apical foramen to a length of 5 mm. Thus, the average apical foramen
      diameters in groups A, B, C and D were approximately 0.82 mm, 1.02 mm, 1.22mm and
      1.5 mm, respectively. The teeth were then mounted in 1% agar and four EALs were
      used: Root ZX, Foramatron D10, Apex NRG and Apit 7. For electronic measurement,
      sizes #10 and #80, #10 and #100, #10 and #120, and #10 and #140 K-files were used
      for groups A, B, C and D, respectively. During electronic measurement the canals
      were flushed with 6% sodium hypochlorite solution. RESULTS: Three-way ANOVA and
      Bonferroni test showed that EAL, file size and foramen size all had a significant
      influence on the measurement error (P<0.0001), with all the interactions between
      these three factors being significant (P<0.0001). CONCLUSIONS: The four EALs were
      unreliable to determine the working length of teeth with a wide apical foramen,
      when using a small size file. The Root ZX and Foramatron D10 showed significantly
      better scores than the other two EALs and may be more reliable to determine the
      working length of teeth with a wide apical foramen, if a tight-fit file is used.

PMID- 17037895
TI  - The use of a dental implant as an abutment in three unit implant-tooth supported
      fixed partial denture: a case report and 32 month follow-up.
AB  - The combined use of dental implants and teeth as abutments in fixed partial
      dentures may offer advantages to both patients and practitioners in certain
      clinical situations. An implant-tooth retained prosthesis may reduce surgical
      intervention and cost to the patient. It may also mean that anatomical
      restrictions to the provision of an implant-retained fixed prosthesis may be
      overcome. In this case report, the steps in provision of a three unit implant-to
      tooth fixed partial denture are described and the treatment planning and
      prognosis of a restoration of this type are discussed.

PMID- 17037897
TI  - Prevention and management of dental decay in the preschool child.

PMID- 17037896
TI  - Intra-oral distribution of caries in South Australian children.

PMID- 17037898
TI  - They call her 'Lucy's daughter'.

PMID- 17037899
TI  - The benefits of busy.

PMID- 17037900
TI  - Getting ready to roll.

PMID- 17037901
TI  - The monster at our door.

PMID- 17037902
TI  - 'I feel good, I feel alive'.

PMID- 17037903
TI  - Beyond statins.

PMID- 17037904
TI  - Frightening--and fantastic.

PMID- 17037905
TI  - On-line drug metabolism in capillary electrophoresis. 1. Glucuronidation using
      rat liver microsomes.
AB  - A rat liver microsome pseudostationary phase has been used for the on-line
      capillary electrophoresis monitoring of glucuronidation. Uridine diphosphate
      glucuronosyltransferase (EC 2.4.1.17) containing microsomes was isolated from rat
      liver and directly injected onto neutrally coated capillary containing polymeric
      replaceable gels followed by injection of the substrate mixture. On-line
      glucuronidation was observed within 15 min without any sample preparation. The
      factors affecting the separation of glucuronides and parent compounds were
      investigated by varying the applied electric fields and the size (length and
      internal diameter) of capillary. The Michaelis-Menten parameters (Km and Vmax)
      for the glucuronidation of 4-methyl-7-hydroxy coumarin and 4-nitrophenol were
      determined using the CE method and by off-line microsomal incubation. No
      significant differences were observed for Km and Vmax values for 4-methyl-7
      hydroxycoumarin and 4-nitrophenol between on-line and off-line glucuronidation of
      these two compounds. This method was also used to determine the inhibition
      constant (IC50 value) for the competitive inhibition of morphine glucuronidation
      by codeine, IC50 (on-line) = 170 vs 580 microM (off-line). The results
      demonstrate that this method can be used to screen for the glucuronidation of
      test compounds and should reduce the time required for this screening process.

PMID- 17037906
TI  - Visualizing ion electromigration during isotachophoretic separations with
      capillary isotachophoresis-NMR.
AB  - Sample stacking techniques in electrophoresis are gaining popularity due to their
      ability to provide improved sensitivity and separation efficiency. The principles
      behind sample stacking and electrophoretic migration have been studied
      extensively. Nevertheless, there are still a number of observations and
      descriptions of ionic boundaries and migration modes for which the underlying
      principles are not yet fully understood. For example, the behavior of capillary
      isotachophoresis (cITP) systems that exhibit self-sharpening effects can be
      complex, especially when the buffer systems contain many ionic components. In
      this work, cITP coupled with 1H NMR detection is used to study electrophoretic
      migration of ions in both anionic and cationic cITP. A significant advantage of
      1H NMR over other detection methods is the high specificity of this method,
      allowing detection of individual buffer and analyte constituents within the
      migration zones.

PMID- 17037907
TI  - A gas-phase chemiluminescence-based analyzer for waterborne arsenic.
AB  - We show a practical sequential injection/zone fluidics-based analyzer that
      measures waterborne arsenic. The approach is capable of differentiating between
      inorganic As(III) and As(V). The principle is based on generating AsH3 from the
      sample in a confined chamber by borohydride reduction at controlled pH, sparging
      the chamber to drive the AsH3 to a small reflective cell located atop a
      photomultiplier tube, allowing it to react with ozone generated from ambient air,
      and measuring the intense chemiluminescence that results. Arsine generation and
      removal from solution results in isolation from the sample matrix, avoiding the
      pitfalls encountered in some solution-based analysis techniques. The differential
      determination of As(III) and As(V) is based on the different pH dependence of the
      reducibility of these species to AsH3. At pH < or =1, both As(III) and As(V) are
      quantitatively converted to arsine in the presence of NaBH4. At a pH of 4-5, only
      As(III) is converted to arsine. In the present form, the limit of detection (S/N
      = 3) is 0.05 microg/L As at pH < or =1 and 0.09 microg/L As(III) at pH
      approximately 4-5 for a 3-mL sample. The analyzer is intrinsically automated and
      requires 4 min per determination. It is also possible to determine As(III) first
      at pH 4.5 and then determine the remaining As in a sequential manner; this
      requires 6 min. There are no significant practical interferences. A new
      borohydride solution formulation permits month-long reagent stability.

PMID- 17037908
TI  - Atom-transfer radical graft polymerization initiated directly from silica applied
      to functionalization of stationary phases for high-performance liquid
      chromatography in the hydrophilic interaction chromatography mode.
AB  - Initiation of atom-transfer radical polymerization of a number of monomers
      (styrene, methyl acrylate, 3-[N,N-dimethyl-N-(methacryloyloxyethyl)ammonium]
      propanesulfonate, butyl methacrylate, 2,3-epoxypropyl methacrylate) directly from
      chlorinated porous silica particles has been performed. The grafting has been
      confirmed and evaluated by Fourier transform infrared spectroscopy and X-ray
      photoelectron spectroscopy. This initiation technique results in a hydrolytically
      stable initial Si-C bond, tethering the polymer to the silica substrate. The
      resulting grafted particles have been used as separation materials for both
      reversed-phase and hydrophilic interaction chromatography.

PMID- 17037909
TI  - Nanomechanical detection of DNA melting on microcantilever surfaces.
AB  - We observe surface stress changes in response to thermal dehybridization, or
      melting, of double-stranded DNA (dsDNA) oligonucleotides that are grafted on one
      side of a microcantilever beam. Changes in surface stress occur when one
      complementary DNA strand melts and diffuses away from the other, resulting in
      alterations of the electrostatic, counterionic, and hydration interaction forces
      between the remaining neighboring surface-grafted DNA molecules. We have been
      able to distinguish changes in the melting temperature of dsDNA as a function of
      salt concentration and oligomer length. This technique also highlights
      differences between surface immobilized and solution DNA melting dynamics, which
      allows us to better understand the stability of DNA on surfaces. The transduction
      of phase transitions into a mechanical signal is ubiquitous for DNA, making
      cantilever-based detection a widely useful and complementary alternative to
      calorimetric and fluorescence measurements.

PMID- 17037910
TI  - Robust estimation of peptide abundance ratios and rigorous scoring of their
      variability and bias in quantitative shotgun proteomics.
AB  - The abundance ratio between the light and heavy isotopologues of an isotopically
      labeled peptide can be estimated from their selected ion chromatograms. However,
      quantitative shotgun proteomics measurements yield selected ion chromatograms at
      highly variable signal-to-noise ratios for tens of thousands of peptides. This
      challenge calls for algorithms that not only robustly estimate the abundance
      ratios of different peptides but also rigorously score each abundance ratio for
      the expected estimation bias and variability. Scoring of the abundance ratios,
      much like scoring of sequence assignment for tandem mass spectra by peptide
      identification algorithms, enables filtering of unreliable peptide quantification
      and use of formal statistical inference in the subsequent protein abundance ratio
      estimation. In this study, a parallel paired covariance algorithm is used for
      robust peak detection in selected ion chromatograms. A peak profile is generated
      for each peptide, which is a scatterplot of ion intensities measured for the two
      isotopologues within their chromatographic peaks. Principal component analysis of
      the peak profile is proposed to estimate the peptide abundance ratio and to score
      the estimation with the signal-to-noise ratio of the peak profile (profile signal
      to-noise ratio). We demonstrate that the profile signal-to-noise ratio is
      inversely correlated with the variability and bias of peptide abundance ratio
      estimation.

PMID- 17037911
TI  - ProRata: A quantitative proteomics program for accurate protein abundance ratio
      estimation with confidence interval evaluation.
AB  - A profile likelihood algorithm is proposed for quantitative shotgun proteomics to
      infer the abundance ratios of proteins from the abundance ratios of isotopically
      labeled peptides derived from proteolysis. Previously, we have shown that the
      estimation variability and bias of peptide abundance ratios can be predicted from
      their profile signal-to-noise ratios. Given multiple quantified peptides for a
      protein, the profile likelihood algorithm probabilistically weighs the peptide
      abundance ratios by their inferred estimation variability, accounts for their
      expected estimation bias, and suppresses contribution from outliers. This
      algorithm yields maximum likelihood point estimation and profile likelihood
      confidence interval estimation of protein abundance ratios. This point estimator
      is more accurate than an estimator based on the average of peptide abundance
      ratios. The confidence interval estimation provides an "error bar" for each
      protein abundance ratio that reflects its estimation precision and statistical
      uncertainty. The accuracy of the point estimation and the precision and
      confidence level of the interval estimation were benchmarked with standard
      mixtures of isotopically labeled proteomes. The profile likelihood algorithm was
      integrated into a quantitative proteomics program, called ProRata, freely
      available at www.MSProRata.org.

PMID- 17037912
TI  - Surface-based lithium ion sensor: An electrode derivatized with a self-assembled
      monolayer.
AB  - Self-assembled monolayers (SAMs) of 21-(16-mercaptohexadecan-1-oyl)-4,7,13,16
      tetraoxa-1,10,21-triazabicyclo[8.8.5]tricosane-19,23-dione were prepared on gold.
      Characterization of the SAMs was carried out by sessile drop contact angle,
      ellipsometry, grazing angle FT-IR spectroscopy, and electrochemical techniques.
      The cation recognition properties of the SAM were studied by cyclic voltammetry
      and impedance spectroscopy. The films show moderate selectivity for detection of
      Li+ ions in solution over K+ and Na+, with selectivity values calculated to be
      log K(Li+,Na+) approximately -1.30 and log K(Li+,K+) approximately -0.92. To the
      best of our knowledge, this is the first demonstration of a lithium sensor
      fabricated using self-assembled monolayer technology.

PMID- 17037913
TI  - Cell-free bioassay for measurement of dioxins based on fluorescence enhancement
      of fluorescein isothiocyanate-labeled DNA probe.
AB  - This study aims to develop a rapid and sensitive cell-free bioassay of dioxins.
      It is known that dioxin ligand can bind heterodimeric aryl hydrocarbon receptor
      (AhR) and triggers the formation of the complex of dioxin-AhR, AhR nuclear
      translocator (ARNT), and dioxin-responsive element (DRE) region of the DNA. The
      hypothesis of the proposed method is that if FITC were labeled at the DRE
      sequence, its fluorescence intensity would be enhanced when the complex forms
      because the interaction interface of the binding components (AhR, ARNT, and DRE)
      creates a rather hydrophobic condition that is in favor of FITC emission. Effects
      of modification site of FITC on the DNA probes on binding efficiency between the
      complex components and fluorescence emission enhancement were evaluated by
      surface plasmon resonance and fluorescence analysis, respectively. Results showed
      that the labeling site at the second base at the 5' end apart from the core
      region (5'-TNGCGTG-3') of DRE did not obviously interfere with the binding
      between the DNA probe and dioxin-AhR/ARNT hybrid but presented significant
      fluorescence emission enhancement. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was
      used as the typical toxin in this study. The method had a linear range of 1-100
      pM, with detection limit of 0.1 pM (0.64 fg/assay) and coefficient of variation
      of 5.6% (n = 10, 50 pM TCDD in transformed cytosol). The whole detection cycle
      was approximately 4 h. The method was also used to estimate the toxic equivalents
      (TEQ) of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD) and 1,2,3,4,7,8
      hexachlorodibenzo-p-dioxin (HxCDD). Measurement of TEQs of the mixture of TCDD,
      PeCDD, and HxCDD were highly consistent with the predicted data. The average
      recovery using fly ash extract was approximately 93%.

PMID- 17037914
TI  - MALDI-MS direct tissue analysis of proteins: Improving signal sensitivity using
      organic treatments.
AB  - Direct tissue analysis using MALDI-MS allows the generation of profiles while
      maintaining the integrity of the tissue, displaying cellular localizations and
      avoiding tedious extraction and purification steps. However, lower spectral
      quality can result from direct tissue analysis due to variations in section
      thickness, the nature of the tissue, and the limited access to peptides/proteins
      due to high lipid content. To improve signal sensitivity, we have developed a
      tissue-washing procedure using organic solvents traditionally used for lipid
      extraction, i.e., CHCl3, hexane, toluene, acetone, and xylene. The increased
      detection for peptides/proteins (m/z 5000-30,000) is close to 40% with chloroform
      or xylene, and 25% with hexane, while also improving sample reproducibility for
      each solvent used in the present study. This strategy improved matrix
      cocrystallization with tissue peptides/proteins and more importantly with
      cytoplasmic proteins without delocalization. The extracted lipids were
      characterized by nanoESI-QqTOF/MS/MS using the precursor ion mode, lithium
      adducts, or both and were identified as phospholipids including
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and
      lysophosphatidylinositol, confirming membrane lipid extraction from the tissues.

PMID- 17037915
TI  - Signal enhancement in HPLC/microcoil NMR using automated column trapping.
AB  - A new HPLC NMR system is described that performs analytical separation,
      preconcentration, and NMR spectroscopy in rapid succession. The central component
      of our method is the online preconcentration sequence that improves the match
      between postcolumn analyte peak volume and microcoil NMR detection volume.
      Separated samples are collected on to a C18 guard column with a mobile phase
      composed of 90% D2O/10% acetonitrile-D3 and back-flushed to the NMR microcoil
      probe with 90% acetonitrile-D3/10% D2O. To assess the performance of our unit, we
      separated a standard mixture of 1 mM ibuprofen, naproxen, and phenylbutazone
      using a commercially available C18 analytical column. The S/N measurements from
      the NMR acquisitions indicated that we achieved signal enhancement factors up to
      10.4 (+/-1.2)-fold. Furthermore, we observed that preconcentration factors
      increased as the injected amount of analyte decreased. The highest concentration
      enrichment of 14.7 (+/-2.2)-fold was attained injecting 100 microL of solution of
      0.2 mM (approximately 4 microg) ibuprofen.

PMID- 17037916
TI  - In situ surface sampling of biological objects and preconcentration of their
      volatiles for chromatographic analysis.
AB  - This report describes a rolling stir bar sampling procedure for volatile organic
      compounds (VOCs) present on various biological surfaces. In combination with
      thermal desorption/gas chromatography/mass spectrometry, this analytical
      technique was initially tested for quantitative profiling of human skin VOCs. It
      is also applicable to additional hydrophobic surfaces such as agricultural
      products, plant materials, and bird feathers. Use of embedded internal standards
      provides highly reproducible and quantitative results for a wide variety of
      sampled trace components. The samples of collected human skin VOCs and standards
      were found stable under cool storage conditions for at least 14 days, making this
      approach suitable for field biological and agricultural studies. Additionally,
      this methodology appears to have potential for forensic and toxicological
      investigations, as suggested through the analyses of VOC profiles of the human
      thumb prints recovered from a nonbiological smooth surface.

PMID- 17037917
TI  - Formation of silver nanoparticles in poly(perfluorosulfonic) acid membrane.
AB  - The formation of silver nanoparticles by chemical reduction of Ag+-loaded Nafion
      117 membrane with NaBH4 was studied using radioactivity tagged ions. The
      counterion-exchange method (Ag(m)+ <--> Na(s)+) was used to obtain a membrane
      sample with a varying proportion of Ag+ ions. The X-ray elemental mapping across
      the thickness of the membrane by energy-dispersive X-ray spectrometer attached to
      the environmental scanning electron microscope (ESEM/EDAX) indicated that Na+ and
      Ag+ were uniformly distributed in the membrane samples before reduction. The
      average size of nanoparticles formed after reduction was found to be 15 +/- 3 nm,
      irrespective of the concentration of silver ions present in the membrane before
      reduction. Energy-dispersive X-ray fluorescence (EDXRF) analyses of the membrane
      samples, carried out before and after reduction, indicated that the Ag
      concentration on the membrane surface was considerably increased after reduction.
      EDXRF measurements of the membrane samples, obtained from reduction carried out
      in a dead end cell, indicated that Ag nanoparticles were formed only on the
      membrane surface exposed to NaBH4 solution. Reduction carried out with NaBH4
      tagged with 22Na showed that the formation of Ag nanoparticles involved exchange
      of Ag+ ions from ion-exchange sites in the interior of the membrane with Na+
      ions, followed by reduction of Ag+ ions with BH4- ions at the surface of
      membrane. The study of self-diffusion of water, Na+, and Cs+ ions in the membrane
      loaded with Ag nanoparticles indicated that formation of Ag nanoparticles did not
      affect the diffusional transport properties of the membrane. The ion-exchange
      capacity and water uptake capacity were also not affected by the formation of Ag
      nanoparticles in the membrane. The spatial distribution of Ag nanoparticles
      across the thickness of the membrane obtained by ESEM/EDAX showed that Ag
      nanoparticles were confined to a few-micrometer surface layer of the membrane.
      Based on these observations, an attempt has been made to explain the mechanism of
      the formation of Ag nanoparticles in the membrane.

PMID- 17037918
TI  - Quantification and identification of components in solution mixtures from 1D
      proton NMR spectra using singular value decomposition.
AB  - One-dimensional proton NMR spectra of complex solutions provide rich molecular
      information, but limited chemical shift dispersion creates peak overlap that
      often leads to difficulty in peak identification and analyte quantification.
      Modern high-field NMR spectrometers provide high digital resolution with improved
      peak dispersion. We took advantage of these spectral qualities and developed a
      quantification method based on linear least-squares fitting using singular value
      decomposition (SVD). The linear least-squares fitting of a mixture spectrum was
      performed on the basis of reference spectra from individual small-molecule
      analytes. Each spectrum contained an internal quantitative reference (e.g., DSS
      d6 or other suitable small molecules) by which the intensity of the spectrum was
      scaled. Normalization of the spectrum facilitated quantification based on peak
      intensity using linear least-squares fitting analysis. This methodology provided
      quantification of individual analytes as well as chemical identification. The
      analysis of small-molecule analytes over a wide concentration range indicated the
      accuracy and reproducibility of the SVD-based quantification. To account for the
      contribution from residual protein, lipid or polysaccharide in solution, a
      reference spectrum showing the macromolecules or aggregates was obtained using a
      diffusion-edited 1D proton NMR analysis. We demonstrated this approach with a
      mixture of small-molecule analytes in the presence of macromolecules (e.g.,
      protein). The results suggested that this approach should be applicable to the
      quantification and identification of small-molecule analytes in complex
      biological samples.

PMID- 17037919
TI  - Scanning temperature gradient focusing.
AB  - Temperature gradient focusing (TGF) is a recently developed technique for the
      simultaneous concentration and electrophoretic separation of ionic analytes in
      microfluidic channels. One drawback to TGF as it has previously been described is
      the limited peak capacity; only a small number of analyte peaks (approximately 2
      3) can be simultaneously focused and separated. In this paper, we report on a
      variation of the TGF method whereby the bulk flow rate is varied over time so
      that a large number of analytes can be sequentially focused, moved past a fixed
      detection point, and flushed to waste. In addition to improved peak capacity, the
      detection limits of the scanning TGF method can be adjusted on-the-fly, as needed
      for different samples. Finally, scanning TGF provides a technique by which high
      resolution, high-peak-capacity electrophoretic separations can be performed in
      simple, straight, and short microfluidic channels.

PMID- 17037920
TI  - Electron capture dissociation as structural probe for noncovalent gas-phase
      protein assemblies.
AB  - Electron capture dissociation (ECD) of proteins in Fourier transform ion
      cyclotron resonance mass spectrometry usually leads to charge reduction and
      backbone-bond cleavage, thereby mostly retaining labile, intramolecular
      noncovalent interactions. In this report, we evaluate ECD of the 84-kDa
      noncovalent heptameric gp31 complex and compare this with sustained off-resonance
      irradiation collisionally activated dissociation (SORI-CAD) of the same protein.
      Unexpectedly, the 21+ charge state of the gp31 oligomer exhibits a main ECD
      pathway resulting in a hexamer and monomer, disrupting labile, intermolecular
      noncovalent bonds and leaving the backbone intact. Unexpectedly, the charge
      separation over the two products is highly proportional to molecular weight. This
      indicates that a major charge redistribution over the subunits of the complex
      does not take place during ECD, in contrast to the behavior observed when using
      SORI-CAD. We speculate that the ejected monomer retains more of its original
      structure in ECD, when compared to SORI-CAD. ECD of lower charge states of gp31
      does not lead to dissociation of noncovalent bonds. We hypothesize that the
      initial gas-phase structure of the 21+ charge state is significantly different
      from the lower charge states. These structural differences result in the
      different reaction pathways when using ECD.

PMID- 17037921
TI  - Protein nanopatterns and biosensors using gold binding polypeptide as a fusion
      partner.
AB  - An efficient strategy for immobilizing proteins on a gold surface was developed
      by employing the gold binding polypeptide (GBP) as a fusion partner. Using the
      enhanced green fluorescent protein (EGFP), severe acute respiratory syndrome
      coronavirus (SARS-CoV) envelope protein (SCVme), and core streptavidin (cSA) of
      Streptomyces avidinii as model proteins, specific immobilization of the GBP
      fusion proteins onto the gold nanoparticles and generation of protein
      nanopatterns on the bare gold surface were demonstrated. The GBP-fused SCVme
      bound to gold nanoparticles successfully interacted with its antibody and showed
      changes in absorbance and color, allowing efficient diagnosis of SARS-CoV. The
      fusion proteins could be successfully immobilized on the gold surface by
      nanopatterning and microcontact printing as examined by atomic force microscopy
      and surface plasmon resonance analysis. The poly(dimethylsiloxane) microfluidic
      channels were created on the gold surface and were used for antigen-antibody and
      DNA-DNA interaction studies. Specific immobilization of GBP-EGFP fusion protein
      and its interaction with the antibody in the microchannels could be demonstrated.
      By immobilizing the DNA probe through the use of GBP-fused cSA, specific
      hybridization of the target DNA prepared from Salmonella could also be achieved.
      The GBP-fusion method allows immobilization of proteins onto the gold surface
      without surface modification and in bioactive forms suitable for studying protein
      protein, DNA-DNA, and other biomolecular interaction studies. Furthermore, these
      studies can be carried out in a microfluidic system, which allows high-throughput
      analysis of biomolecular interactions.

PMID- 17037922
TI  - Mesoscale energy deposition footprint model for kiloelectronvolt cluster
      bombardment of solids.
AB  - Molecular dynamics simulations have been performed to model 5-keV C60 and Au3
      projectile bombardment of an amorphous water substrate. The goal is to obtain
      detailed insights into the dynamics of motion in order to develop a
      straightforward and less computationally demanding model of the process of
      ejection. The molecular dynamics results provide the basis for the mesoscale
      energy deposition footprint model. This model provides a method for predicting
      relative yields based on information from less than 1 ps of simulation time.

PMID- 17037923
TI  - In vivo glucose measurement by surface-enhanced Raman spectroscopy.
AB  - This paper presents the first in vivo application of surface-enhanced Raman
      scattering (SERS). SERS was used to obtain quantitative in vivo glucose
      measurements from an animal model. Silver film over nanosphere surfaces were
      functionalized with a two-component self-assembled monolayer, and subcutaneously
      implanted in a Sprague-Dawley rat such that the glucose concentration of the
      interstitial fluid could be measured by spectroscopically addressing the sensor
      through an optical window. The sensor had relatively low error (RMSEC = 7.46
      mg/dL (0.41 mM) and RMSEP = 53.42 mg/dL (2.97 mM).

PMID- 17037924
TI  - Antigen-epitope retrieval to facilitate proteomic analysis of formalin-fixed
      archival brain tissue.
AB  - Formalin is a routine fixative facilitating tissue preservation and
      histopathology. Proteomic techniques require freshly frozen specimens, which are
      often difficult to procure, and methods facilitating proteomic analysis of
      archival formalin-fixed brain tissue are lacking. We employed antigen-epitope
      retrieval principles to facilitate proteomic analysis of brain tissue that had
      been fixed and stored in formalin for 3-7 years. Twenty-micrometer-thick
      cryopreserved OCT-embedded sections from inferior temporal cortex of human (7
      years in formalin) or mouse brain specimens (3 years in formalin) were
      hematoxylin-/eosin-stained. Approximately 16-64-mm2 areas of the tissue sections
      were manually scraped off slides, or approximately 2 mm2 of human brain cortex
      was captured off membrane-coated slides using laser microdissection. Tissue was
      treated using various pH and temperature conditions prior to trypsin digestion
      and nano-LC-MS/MS. The largest number of proteins were retrieved by
      solubilization at pH 9 at 95 degrees C for 1 h; treatments at pH 4 or 6 at 25 or
      65 degrees C were generally ineffective. Three-year formalin-fixed murine tissue
      did not yield more proteins compared to human tissue. Use of formalin-fixed
      tissue for proteomics is an invaluable tool for medical research. The combination
      of proteomics and microdissection enables selective enrichment and identification
      of novel, unique, or abundant proteins that may be important in pathogenesis.

PMID- 17037925
TI  - Chitosan as a polymer for pH-induced DNA capture in a totally aqueous system.
AB  - A novel DNA solid-phase extraction protocol based on the pH-dependent charge of
      chitosan was developed specifically for low-volume DNA extraction on microchips.
      The method uses chitosan-coated beads to extract DNA at pH 5 and release it from
      the chitosan at pH 9. DNA extraction efficiency as high as 92% could be attained,
      even from complex samples such as human blood containing significant amounts of
      protein. Using this method, PCR inhibitors that are typically used in DNA
      extraction procedures (e.g., chaotropic salts, 2-propanol) can be avoided, making
      the method more conducive to downstream sample processing using PCR. A high
      density multichannel microchip device was then fabricated and the microchannels
      coated with chitosan for DNA extraction in an open channel configuration without
      the need for an additional stationary phase. This design provided a relatively
      high surface area-to-volume ratio for extraction, while retaining the low flow
      resistance commensurate with open channels. With a flow rate of approximately 1
      microL/min during the extraction, the total extraction time was less than 10 min,
      with most of the DNA recovered in the first 2 microL of elution buffer. Using the
      microchip device, extraction efficiencies for lambda-phage DNA and human genomic
      DNA were as high as 67 and 63%, respectively. Human genomic DNA from whole blood
      samples could be extracted in 10 min with an extraction efficiency of 75 +/- 4%
      (n = 3), and the purified DNA was suitable for PCR amplification of a fragment of
      the gelsolin gene. The combination of an entirely aqueous DNA extraction method
      with a high-density, low-flow resistance microchannel pattern sets the stage for
      future integration into microfluidic genomic analysis devices.

PMID- 17037926
TI  - Tetrabutylammonium-induced coacervation in vesicular solutions of alkyl
      carboxylic acids for the extraction of organic compounds.
AB  - The potential of the tetrabutylammonium-induced liquid-liquid-phase separation in
      alkyl carboxylic acid vesicular solutions for the extraction of organic compounds
      prior to liquid chromatography was examined for the first time. The behavior of
      the coacervates yielded from octanoic to oleic acids as a function of the pH and
      salts was investigated. The time required for phase separation depended on the
      length of the carboxylic acid alkyl chain and the experimental procedure (i.e.,
      standing, sonication, centrifugation, stirring, etc.). Theoretical
      preconcentration factors were a function of both surfactant concentration and the
      length of the alkyl chain, and they greatly surpassed those obtained with other
      surfactant-mediated separations (e.g., surfactant-rich phases from
      dodecanesulfonic acid or Triton X-114). Parameters affecting the extraction
      efficiency were assessed. Analytes in a wide polarity/charge range, (e.g., PAHs,
      surfactants, chlorophenols, bisphenols, phthalates, herbicides, amines, dyes, and
      photographic developers) were extracted with high efficiencies on the basis of
      the different types of interactions that the vesicular coacervates can establish
      (i.e., hydrophobic and ionic interactions, hydrogen bonds, and formation of mixed
      aggregates). The coacervates were compatible with the chromatographic
      determination of analytes following UV or MS detection. Their suitability for
      working under real conditions was checked by applying them to the extraction of
      nonionic surfactants [alkylphenol ethoxylates (octyl and nonyl) and alcohol
      ethoxylates (C12-C16)] from raw and treated sewage and to river water samples.
      Analytes in the coacervate were separated and quantified by liquid chromatography
      ion trap mass spectrometry. No cleanup steps were necessary. Recoveries of the
      target compounds in the environmental water samples ranged from 89 to 103%.

PMID- 17037927
TI  - Improving an immunoassay response to related polychlorinated biphenyl analytes by
      mixing antibodies.
AB  - Immunoassays for detection of a class of closely related antigens, e.g., PCBs,
      have often been too specific (responding strongly to some members of the class
      and missing others) and no general method for adjusting the response has been
      described. In this paper, the difference in the response of a model immunoassay
      to different Kanechlors (Japanese commercial mixtures of PCBs, analogous to
      Aroclors in the United States) is reduced from 20- or 50-fold (depending on which
      antibody is used) to 3-fold when the antibodies are mixed at the proper ratio. A
      mathematical model based on competitive binding of two antibodies for up to four
      antigens has been developed and used to describe the assay performance and to
      predict optimum mix ratios for the antibodies used. The model (based on separate
      measurement of each antibody's effective Kd for each Kanechlor) provides an
      excellent fit to the measured mixed antibody assay response. The model is also
      successful in identifying cases where mixing monoclonal antibodies will not
      improve the response. It is thought the method described will have applicability
      in a variety of cases where the analytical goal is semiquantitative screening
      based on the total quantity of an unknown mixture of related compounds.

PMID- 17037928
TI  - Microwave-supported preparation of alpha-cellulose for analysis of delta13C in
      tree rings.
AB  - The microwave technique is found to be very applicable for the preparation of
      alpha-cellulose from wood samples and can be recommended for analyzing the stable
      carbon isotopes in tree rings. At a reaction temperature of 80 degrees C, the
      extraction time can be decreased from 36 h to 15 min. Microwave-supported
      prepared cellulose contains more amorphous constituents, resulting in a
      relatively higher reactivity and amenability for a following nitration with
      regard to determination of nonexchangeable hydrogen. The delta18O values of
      microwave-enhanced extracted cellulose remain significantly lighter than
      reference values, possibly as a result of an increased oxygen isotope exchange
      between bleaching solution and cellulose under conditions of high energy input.
      Therefore, this technique cannot be recommended for oxygen isotope analyses in
      wood cellulose.

PMID- 17037929
TI  - L-histidine imprinted synthetic receptor for biochromatography applications.
AB  - We have proposed novel surface-imprinted beads for selective separation of
      cytochrome c (cyt c) by N-methacryloyl-(L)-histidine-copper(II) [MAH-Cu(II)] as a
      new metal-chelating monomer via metal coordination interactions and histidine
      template. We have combined molecular imprinting with the ability of histidine to
      chelate metal ions to create ligand exchange beads suitable for the binding of
      cyt c (surface histidine exposed protein). The histidine imprinted beads were
      produced by suspension polymerization of MAH-Cu(II)-L-histidine and ethylene
      glycol dimethacrylate. After polymerization, the template (L-histidine) was
      removed from the beads using methanolic KOH, thus getting histidine imprinted
      metal-chelate beads. L-Histidine imprinted metal-chelate beads can be used
      several times without considerable loss of cyt c adsorption capacity. The
      association constant (Ka) for the specific interaction between the template
      imprinted polymer and the template (L-histidine) itself were determined by
      Scatchard plots using L-histidine imprinted beads and found as 58,300 M(-1).
      Finally, we have used these histidine imprinted beads for cyt c and ribonuclease
      A (surface histidine exposed proteins) and enantiometric separation of D- and L
      histidine by FPLC.

PMID- 17037930
TI  - Structural features of the L-argininamide-binding DNA aptamer studied with ESI
      FTMS.
AB  - The 24-mer DNA aptamer of Harada and Frankel (Harada, K.; Frankel, A. D. EMBO J.
      1995, 14, 5798-5811) that binds L-argininamide (L-Arm) was studied by
      electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). This DNA
      folds into a stem and loop such that the loop is able to engulf L-Arm. As
      controls, two derivatives of the same base composition, one with the same stem
      but a scrambled loop and the other with no ability to form a secondary structure,
      were studied. The two DNAs that could fold into stem-loop structures showed a
      more negatively charged distribution of ions than the linear control. This
      tendency was preserved in the presence of ligand; complexes expected to have more
      secondary structure had ions with more negative charges. Distinct species
      corresponding to no, one, and two bound L-Arm molecules were observed for each
      DNA. The fractional peak intensities were fit to a straightforward binding model
      and binding constants were obtained. Thus, ESI-FTMS can provide both qualitative
      and quantitative data regarding the structure of DNA and its interactions with
      noncovalent ligands.

PMID- 17037932
TI  - Determination of the bulk cobalt valence state of co-perovskites containing
      surface-adsorbed impurities.
AB  - We used thermogravimetric hydrogen reduction and iodometric titration to
      determine the bulk valence state of cobalt in Co-perovskites containing surface
      carbonate hydroxide or hydroxyl groups. It could be shown that thermogravimetric
      hydrogen reduction experiments are very sensitive to volatile surface groups, but
      due to their volatility, they can be specified and the bulk valence state of
      cobalt can still be deduced from these experiments. The iodometric titration is
      less sensitive to small volatile surface impurities, but precaution has to be
      taken that oxygen or iodine does not escape from the solution during dissolution
      of the sample. Best results were obtained if the sample was titrated during
      dissolution in a closed argon floated titration apparatus. We tested the two
      methods using LaCoO3 perovskite as a sample with a known valence state. Both
      methods delivered satisfactory results, and the valence state could be determined
      with an accuracy of better than 1%.

PMID- 17037931
TI  - Profiling signaling peptides in single mammalian cells using mass spectrometry.
AB  - The peptide content of individual mammalian cells is profiled using matrix
      assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry.
      Both enzymatic and nonenzymatic procedures, including a glycerol cell
      stabilization method, are reported for the isolation of individual mammalian
      cells in a manner compatible with MALDI MS measurements. Guided microdeposition
      of MALDI matrix allows samples to be created with suitable analyte-to-matrix
      ratios. More than 15 peptides are observed in individual rat intermediate
      pituitary cells. The combination of accurate mass data, expected cleavages by
      proteolytic enzymes, and postsource decay sequencing allows identification of 14
      of these peptides as pro-opiomelanocortin prohormone-derived molecules. These
      protocols permit the classification of individual mammalian cells by peptide
      profile, the elucidation of cell-specific prohormone processing, and the
      discovery of new signaling peptides on a cell-to-cell basis in a wide variety of
      mammalian cell types.

PMID- 17037933
TI  - Generation of ultrahigh peak capacity LC separations via elevated temperatures
      and high linear mobile-phase velocities.
AB  - The use of a combination of ultraperformance liquid chromatography at
      approximately 11,000 psi on sub 2-microm particles combined with reversed-phase
      gradient chromatography at a temperature of 90 degrees C is described as applied
      to the analysis of endogenous and drug metabolites in human and animal urine. By
      using elevated temperatures, back pressures can be reduced while maintaining high
      flow rates and chromatographic efficiency, with peaks 1-3 s wide at the base.
      Application to urine samples provided a peak capacity of approximately 700 for a
      10-min analysis and greater than approximately 1000 in 1 h. Despite the narrow
      nature of the peaks, good quality mass spectra were also obtained, allowing the
      identification of typical drug and endogenous metabolites. These ultra-high
      resolution chromatograms should be ideal for the analysis of complex samples in,
      for example, metabolite identification, impurity identification, and
      metabonomic/metabolomic studies. Applications in natural product analysis and
      proteomics can also be envisaged.

PMID- 17037934
TI  - Measurement of ammonia in human breath with a liquid-film conductivity sensor.
AB  - Measurement of breath NH3 is of interest in clinical applications as it can be
      used as a measure of kidney/liver functions as well as halitosis. We have
      developed a liquid-film conductivity sensor to measure NH3 in human breath. A
      film of dilute H2SO4 is formed on the top of two metal capillary tubes placed in
      a concentric annular arrangement. The tube exterior has been specially treated to
      render it hydrophilic. As breath passes over the sensor tip, the film collects
      NH3 and the solution conductivity (measured by the concentric capillaries
      functioning as electrodes) decreases accordingly. This initial rate of
      conductivity decrease was determined to be the best metric (most rapid and least
      dependent on breath pCO2) for ammonia, relative to time to attain complete
      neutralization (conductivity minimum) or the final rate of conductivity increase
      as more ammonia dissolves after neutralization. The absorbing solution
      composition was optimized so that CO2 does not interfere. Both dynamic
      measurement using mask sampling and offline balloon sampling were performed.
      Ammonia readily absorbs on surfaces when significant concentrations of water
      vapor are present. As such, memory effects are common when analyzing human breath
      for ammonia. This problem was successfully eliminated. The results from this
      sensor agreed well with data obtained by a solution-phase fluorometric technique
      using a porous membrane diffusion scrubber and o-phthalaldehyde derivatization
      chemistry. For breath CO2 measurement, the applicability of a similar sensor that
      relies on a NaOH film was also demonstrated.

PMID- 17037935
TI  - Injection port derivatization following ion-pair hollow fiber-protected liquid
      phase microextraction for determining acidic herbicides by gas
      chromatography/mass spectrometry.
AB  - Injection port derivatization following ion-pair hollow fiber-protected liquid
      phase microextraction (LPME) for the trace determination of acidic herbicides
      (2,4-dichlorobenzoic acid, 2,4-dichlorophenoxyacetic acid, 2-(2,4
      dichlorophenoxy)propionic acid, 3,5-dichlorobenzoic acid, 2-(2,4,5
      trichlorophenoxy)propionic acid) in aqueous samples by gas chromatography/mass
      spectrometry (GC/MS) was developed. Prior to GC injection port derivatization,
      acidic herbicides were converted into their ion-pair complexes with
      tetrabutylammonium chloride in aqueous samples and then extracted by 1-octanol
      impregnated in the hollow fiber. Upon injection, ion pairs of acidic herbicides
      were quantitatively derivatized to their butyl esters in the GC injection port.
      Thus, several parameters related to the derivatization process (i.e., injection
      temperature, purge-off time) were evaluated, and main parameters affecting the
      hollow fiber-protected LPME procedure such as extraction organic solvent, ion
      pair reagent type, pH of aqueous medium, concentration of ion-pair reagent,
      sodium chloride concentration added to the aqueous medium, stirring speed, and
      extraction time profile, optimized. At the selected extraction and derivatization
      conditions, no matrix effects were observed. This method proved good
      repeatability (RSDs <12.3%, n = 6) and good linearity (r2 > or = 0.9939) for
      spiked deionized water samples for five analytes. The limits of detection were in
      the range of 0.51-13.7 ng x L(-1) (S/N =3) under GC/MS selected ion monitoring
      mode. The results demonstrated that injection port derivatization following ion
      pair hollow fiber-protected LPME was a simple, rapid, and accurate method for the
      determination of trace acidic herbicides from aqueous samples. In addition, this
      method proved to be environmentally friendly since it completely avoided open
      derivatization with potentially hazardous reagents.

PMID- 17037936
TI  - Low-cost spectroscopy with a variable multivariate optical element.
AB  - Here, successful realization of a variable multivariate optical element (VMOE)
      based on a transmissive liquid crystal (LC) panel is reported. In contrast to
      conventional multivariate optical elements (MOEs), a single VMOE is a dynamic
      system, allowing measurement of numerous analytes in different mixtures.
      Furthermore, VMOE has superior spectral resolution in comparison to a
      conventional MOE. It is demonstrated here that the system implemented in a Raman
      spectrometer predicts the concentration of each individual component in toluene
      acetonitrile-cyclohexane mixtures with a prediction error of <6% (mass
      percentage). With a dedicated optical design of the setup, a prediction error
      smaller than 2% is expected to be feasible for the current chemical system.

PMID- 17037937
TI  - Analysis of complex protein mixtures with improved sequence coverage using (CE
      MS/MS)n.
AB  - Identification of proteins, in a complex protein mixture, using one-dimensional
      high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
      analysis of its digest, usually suffers from low sequence coverage. There are
      several reasons for the low coverage including undersampling, wide concentration
      dynamic range of the proteins in a complex protein mixture, and wide range of
      electrospray ionization efficiency of peptides under each mobile-phase
      composition. To address this low sequence coverage, we introduce a novel
      technique, (CE-MS/MS)n, which utilizes the most significant advantages of CE
      MS/MS, including economy of sample size, fast analysis time, and high separation
      efficiency, to increase the sequence coverage of a complex protein mixture. Based
      on these characteristics, (CE-MS/MS)n can be performed in which multiple CE-MS/MS
      subanalyses (injections followed by analyses) are analyzed and experimental
      variables are manipulated during each CE-MS/MS subanalysis in order to maximize
      sequence coverage. (CE-MS/MS)n is a practical technique since each CE-MS/MS
      subanalysis consumes <10 nL, and each CE-MS/MS subanalysis takes approximately 10
      min; therefore, several subanalyses can be performed in approximately 1 h
      consuming only nanoliters of the sample. Two techniques have been introduced to
      address the undersampling: (1) (CE-MS/MS)n using dynamic exclusion. In this
      technique, several CE-MS/MS analyses (injection followed by separation) were
      performed in one run using the dynamic exclusion capability of the mass
      spectrometer until all peptide peaks were analyzed by MS/MS. (2) Gas-phase
      fractionation. In this technique, (CE-MS/MS)n is performed by scanning a narrow
      mass range (every approximately 100 m/z) during each CE-MS/MS subanalysis without
      using dynamic exclusion. Under this condition, in each subanalysis, the number of
      peptides available for MS/MS analysis is significantly reduced, and peptides with
      the same nominal masses are analyzed, thereby increasing sequence coverage.
      Additionally, to address the lack of detection of low-level peptides in a mixture
      containing a wide concentration dynamic range, the concentration of the sample
      was systematically increased in each subanalysis (while utilizing dynamic
      exclusion) so that low-intensity peptides would rise above the mass spectrometer
      threshold and, consequently, undergo MS/MS analysis. Moreover, to alter the
      ionization efficiency of peptides with low electrospray ionization efficiency,
      and to change the migration behavior of comigrating peptides under a specific
      liquid composition, the CE background electrolyte was modified in several
      subanalyses to further improve sequence coverage. The combination of the above
      mentioned techniques was applied to the analysis of the tryptic digests of three
      well-characterized protein mixtures: a six-protein mixture with average MW of
      approximately 26,000 (standard I), a six-protein mixture with an average MW
      approximately 49,000 (standard II), and a more complex protein mixture containing
      55 proteins (E. coli ribosomal proteins). In approximately 1 h, when the MS/MS of
      the peptides were manually checked, all peptides that produced peaks under
      electrospray ionization in the scanned range of the analysis (500-2000 m/z) and
      within the practical fragmentation capability of the MS (peptides with MW <3500)
      were identified for standard I by consuming only 200 fmol of each protein. When
      searched against a Swissprot database, the average sequence coverage for the
      standard I, II, and E. coli's ribosomal proteins were 57, 34, and 15%,
      respectively.

PMID- 17037938
TI  - Feedback-independent Pt nanoelectrodes for shear force-based constant-distance
      mode scanning electrochemical microscopy.
AB  - A new generation of platinum nanoelectrodes for constant-distance mode scanning
      electrochemical microscopy (CD-SECM) has been prepared, characterized, and used
      for high spatial resolution electrochemical measurements and visualization of
      electrochemically induced concentration gradients in microcavities. The probes
      have long (1-2 cm), narrow quartz tips that were conically polished and have a Pt
      nanoelectrode that is slightly offset from center. Because of the size and
      location of the electrode on the probe, it does not exhibit SECM feedback while
      approaching the analyzed sample surfaces even to distances within a few hundred
      nanometers. The probe was positioned near the surface while scanning and
      performing electrochemical measurements through use of nonoptical shear force
      control of the tip-to-sample distance. Test structures consisted of cylindrically
      shaped microcavities that are 50 microm in diameter with three individually
      addressable electrodes: a gold disk at 8-microm depth, a crescent-shaped gold
      ring at 4-microm depth along the wall, and a top gold electrode at the rim.
      Different electrodes within the microcavity were used to reduce and oxidize redox
      species in 250 microL of a solution of 5 mM hexaamineruthenium(III) chloride and
      0.1 M potassium chloride, protected from evaporation by mineral oil, while the
      SECM tip followed the topography of the structures and monitored the current from
      the oxidation of [Ru(NH3)6]2+. Electrochemically generated concentration profiles
      were obtained from these complex test structures that are not possible with any
      other SECM technology at this time.

PMID- 17037939
TI  - Conductance maps by electrochemical tunneling spectroscopy to fingerprint the
      electrode electronic structure.
AB  - We describe a methodology to perform reliable tunneling spectroscopy in
      electrochemical media. Sequential in situ tunneling spectra are recorded while
      the electrochemical potential of the electrode is scanned. Spectroscopic data are
      presented as conductance maps or conductograms that show the in situ electronic
      structure of an electrode surface while it undergoes an electrochemical reaction.
      The conductance map or conductogram represents the redox fingerprint of an
      electrode/liquid interface in a specific medium and can serve to predict its
      electrochemical behavior in a quantitative energy scale. The methodology is
      validated studying the reversible oxidation and passivity of an iron electrode in
      borate buffer, and we describe the main quantitative information that can be
      extracted concerning the semiconducting properties of the Fe passive film. This
      methodology is useful to study heterogeneous catalysis, electrochemical sensing
      and bioelectronic systems.

PMID- 17037940
TI  - Electrochemiluminescent detection based on solid-phase extraction at tris(2,2'
      bipyridyl)ruthenium(II)-modified ceramic carbon electrode.
AB  - A sensitive electrochemiluminescent detection scheme by solid-phase extraction at
      Ru(bpy)3(2+)-modified ceramic carbon electrodes (CCEs) was developed. The as
      prepared Ru(bpy)3(2+)-modified CCEs show much better long-term stability than
      other Nafion-based Ru(bpy)3(2+)-modified electrodes and enjoy the inherent
      advantages of CCEs. The log-log calibration plot for dioxopromethazine is linear
      from 1.0 x 10(-9) to 1.0 x 10(-4) mol L(-1) using the new detection scheme. The
      detection limit is 6.6 x 10(-10) mol L(-1) at a signal-to-noise ratio of 3. The
      new scheme improves the sensitivity by approximately 3 orders of magnitude, which
      is the most sensitive Ru(bpy)3(2+) ECL method. The scheme allows the detection of
      dioxopromethazine in a urine sample within 3 min. Since Ru(bpy)3(2+) ECL is a
      powerful technique for determination of numerous amine-containing substances, the
      new detection scheme holds great promise in measurement of free concentrations,
      investigation of protein-drug interactions and DNA-drug interactions,
      pharmaceutical analysis, and so on.

PMID- 17037941
TI  - Grating-coupler assisted infrared reflection absorption spectroscopy for the
      characterization of organic thin films.
AB  - We demonstrate how grating-coupler assisted infrared reflection absorption
      spectroscopy can be used to simultaneously determine the chemical identity and
      relative thickness of organic thin films. With a grating substrate, a threshold
      anomaly associated with passing off of the -1 diffracted order occurs at grazing
      angles of incidence, resulting in a sharp absorbance in the infrared. The
      position of this peak is sensitive to the grating geometry as well as the
      dielectric environment near its surface. Thus, shifts in the peak position can be
      used to determine the relative thickness of adsorbed films or quantify molecular
      adsorption events. To illustrate the characteristics and sensitivity of this
      phenomenon, several samples were prepared and tested, including self-assembled
      alkanethiolate monolayers with 11-mercaptoundecanoic acid, 11-mercapto-1
      undecanol, decanethiol, and a covalently linked layer of bovine serum albumin on
      a commercial, gold-coated grating. For these samples, the position of the
      threshold absorbance peak shifted to lower wavenumbers as film thickness
      increased, which is consistent with calculated shifts based upon an increasing
      refractive index at the interface. The sensitivity of this shift was measured to
      be 3.7 cm(-1) nm(-1). These results illustrate how a grating substrate can be
      exploited in a standard infrared reflectance measurement to provide additional
      information about the relative thickness of adsorbed surface films.

PMID- 17037942
TI  - Atomic force microscopy study of different effects of natural and semisynthetic
      beta-lactam on the cell envelope of Escherichia coli.
AB  - The effects of native and semisynthetic beta-lactam on the surface of E. coli
      cells were investigated using tapping mode atomic force microscopy (AFM). These
      studies were done on both single cell and cell colonies. This allowed us to
      achieve a complete understanding of the effects, since previous related AFM
      analysis was only performed on single cells. Our results indicated that although
      amoxycillin and penicillin could both induce nanoporous damage to the envelope of
      E. coli, the distribution of the pores was different: those induced by penicillin
      were randomly distributed on the cell surface, while those induced by amoxycillin
      were far more numerous and mainly on the two ends of the cell. These findings
      could explain why the effect of amoxycillin is stronger than that of native
      penicillin. Ofloxacin was used as a control due to its inactive membrane, and no
      cell wall damages were observed. Our results demonstrate that AFM is a useful
      tool in discerning and verifying antibiotic mechanisms and can be helpful to
      explain the relationship between chemical structure and the function of
      antibiotics.

PMID- 17037943
TI  - Simultaneous excitation of propagating and localized surface plasmon resonance in
      nanoporous gold membranes.
AB  - Materials multifunctionality for optical sensing of adsorbates has obvious
      advantages-in addition to the potential for greater sensitivity, the different
      length scales associated with a variety of optical phenomena allow a greater
      variety of adsorption characteristics to be examined. Here, we show that
      ultrathin (approximately 100 nm) nanoporous gold membranes possess features of
      both planar metal films that exhibit propagating SPR excitations and nanofeatured
      metals that exhibit localized SPR excitations. This is the first report of such
      multifunctionality in an optically active metal. We give illustrative examples of
      using this material to probe biorecognition reactions and to probe the structure
      evolution of a layer-by-layer deposition of charged dendrimers. Our results are
      consistent with the very different lengths of the tail of the evanescent field
      decays associated with each of these plasmon excitation modes.

PMID- 17037945
TI  - Clinical trials research in pediatrics: strategies for effective collaboration
      between investigator sites and the pharmaceutical industry.
AB  - There is a paucity of clinical trials work in children, which leads to the
      frequent use of off-label and unlicensed medications in this very vulnerable
      group. Clinical trials work in children may be more difficult than in adults, and
      there are certainly ethical constraints. However, the differences between adults
      and children, and at different stages of childhood development, mandate
      strategies to improve this situation rather than continually relying on
      extrapolation from adult studies. Therefore, new strategies have to be
      established between the pharmaceutical industry and pediatric centers to
      facilitate effective trials work. These must be based on a clear and mutual
      understanding of the differences between working with children and adults.
      Disease phenotypes may be completely different in children; for example, wheeze
      in infants is not miniature adult asthma. Clinical trial design must be
      practical, and a trial is more likely to succeed if a simple design is utilized,
      with minimal interference with school work and the work of carers. The new UK
      initiative, 'Medicines for Children', should go a long way towards addressing the
      problem, and increase the evidence base for the utilization of medications in
      pediatric practice.

PMID- 17037947
TI  - Juvenile myoclonic epilepsy: epidemiology, pathophysiology, and management.
AB  - Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome that begins most
      frequently in the early teenage years. It is officially classified as a type of
      idiopathic generalized epilepsy and is often under-recognized or misdiagnosed.
      This syndrome has a strong genetic component with multiple gene mutations being
      associated with the clinical presentation. Based upon genetic associations, there
      may be multiple pathophysiologic mechanisms for the disorder; the pathophysiology
      has not been clearly defined. A diagnosis of JME is made using the clinical
      history and EEG findings. Valproic acid is the primary antiepileptic drug (AED)
      used for JME, but some newer AEDs may be effective alternatives. Selection of an
      appropriate AED is essential to the proper management of JME, because of the
      possibility of exacerbation of seizures by some AEDs and the adverse effect
      profiles of effective drugs. It is important for clinicians to understand JME to
      correctly diagnose and manage patients with this syndrome.

PMID- 17037948
TI  - Polycystic ovary syndrome in adolescents: current and future treatment options.
AB  - Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5-10% of
      women of reproductive age. The pivotal endocrine abnormalities of this syndrome
      are insulin resistance and ovarian and, to a lesser degree, adrenal
      hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as
      the first decade of life by premature pubarche or menarche. Oligoamenorrhea in
      the first postpubarchal years, although very common, may be an early symptom of
      PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth
      weight as well as a family history of diabetes mellitus or premature
      cardiovascular disease are at high risk for developing PCOS. Circulating
      bioavailable testosterone levels are usually elevated, while total testosterone
      may be normal due to low levels of sex hormone-binding globulin. The typical
      sonographic appearance of PCOS ovaries consists of high ovarian volume (>10 mL)
      and the presence of 12 or more follicles in each ovary measuring 2-9 mm in
      diameter. However, this finding is not specific, since it may occur in >20% of
      healthy girls. The therapeutic goals in adolescents with PCOS is first to restore
      bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction
      of bodyweight in this young age group may require the collaboration of the
      pediatrician, dietitian, and psychotherapist. The adolescent should be urged to
      adopt a healthy lifestyle with the aim to maintain a normal body mass index
      throughout adolescence and adult life. The choice of medical therapy depends on
      the clinical presentation. Oral contraceptives are a good option when acne and
      hirsutism are the principal complaints. Adolescents with isolated cycle
      irregularity may be placed on a cyclical progestin regimen to induce withdrawal
      bleeding. Metformin, by decreasing insulin resistance, alleviates many of the
      hormonal disturbances and restores menses in a considerable proportion of
      patients. It may be used alone or in combination with oral contraceptives.
      Independently of medical treatment, restoration and maintenance of bodyweight
      within normal range is of paramount importance.

PMID- 17037946
TI  - Current therapy of inflammatory bowel disease in children.
AB  - Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal
      inflammatory diseases that can present as bloody diarrhea, abdominal pain, and
      malnutrition. Collectively, these disorders are referred to as inflammatory bowel
      disease (IBD). All patients with IBD share a common pathophysiology. However,
      there are a number of developmental, psychosocial, and physiologic issues that
      are unique to the approximate, equals 20% of patients that present during
      childhood or adolescence. These include the possibility of disease-induced delays
      in linear growth or physical development, differences in drug dosing, and the
      changes in social and cognitive development that occur as children move from
      school-age years into adolescence and early adulthood. Gastroenterologists caring
      for these children must therefore develop an optimal regimen of pharmacologic
      therapies, nutritional management, psychologic support, and properly timed
      surgery (when necessary) that will maintain disease remission, minimize disease
      and drug-induced adverse effects, and optimize growth and development. This
      article reviews current approaches to the management of patients with UC and CD
      and highlights issues specific to the treatment of children with IBD. The
      principal medical therapies used to induce disease remission in patients with UC
      are aminosalicylates (for mild disease), corticosteroids (for moderate disease),
      and cyclosporine (ciclosporin) (for severe disease). If a patient responds to the
      induction regimen, maintenance therapies that are used to prevent disease relapse
      include aminosalicylates, mercaptopurine, and azathioprine. Colectomy with
      creation of an ileal pouch anal anastomosis (J pouch) has become the standard of
      care for patients with severe or refractory colitis and results in an improved
      quality of life in most patients. Therefore, the risks associated with using
      increasingly potent immunosuppressant agents must be balanced in each case
      against a patient's desire to retain their colon and avoid a temporary or
      potentially permanent ileostomy. Decisions about drug therapy in the management
      of patients with CD are more complex and depend on both the location (e.g.
      gastroduodenal vs small intestinal vs colonic), as well as the behavior of the
      disease (inflammatory/mucosal vs stricturing vs perforating) in a given patient.
      Induction therapies for CD typically include aminosalicylates and antibiotics
      (for mild mucosal disease), nutritional therapy (including elemental or polymeric
      formulas), corticosteroids (for moderate disease), and infliximab (for
      corticosteroid-resistant or fistulizing disease). Aminosalicylates,
      mercaptopurine, azathioprine, methotrexate, and infliximab can be used as
      maintenance therapies. Because surgical treatment of CD is not curative, it is
      typically reserved for those patients either with persistent symptoms and disease
      limited to a small section of the intestine (e.g. the terminal ileum and cecum)
      or for the management of complications of the disease including stricture or
      abdominal abscess. When surgery is necessary, maintenance medications
      administered postoperatively will postpone recurrence. Patients with UC and CD
      are at risk for the development of micronutrient deficiencies (including folate,
      iron, and vitamin D deficiencies) and require close nutritional monitoring. In
      addition, patients with UC and CD involving the colon are at increased risk of
      developing colon cancer, and should be enrolled into a colonoscopy surveillance
      program after 8-10 years of disease duration.

PMID- 17037949
TI  - Methylphenidate controlled-delivery capsules (EquasymXL, Metadate CD): a review
      of its use in the treatment of children and adolescents with attention-deficit
      hyperactivity disorder.
AB  - Controlled-delivery methylphenidate (methylphenidate CD) [EquasymXL, Metadate
      CD], an oral stimulant, is approved in the US and EU to treat children aged>or=6
      years who have been diagnosed with attention-deficit hyperactivity disorder
      (ADHD). Once-daily methylphenidate CD is generally well tolerated and effective
      in the treatment of children and adolescents with ADHD. Methylphenidate CD
      resulted in superior control of ADHD symptoms compared with osmotic release oral
      system (OROS) methylphenidate over a time period corresponding to that of an
      average school day in a laboratory classroom. In 3-week clinical trials conducted
      in a community setting, methylphenidate CD was superior to placebo and
      noninferior to methylphenidate immediate-release (IR) in the treatment of
      children and adolescents with ADHD. Thus, methylphenidate CD should be considered
      an important primary treatment on its own or in addition to behavioral and
      psychosocial interventions, for when a reduction in ADHD symptoms is required
      during the school day in preference to the evening.

PMID- 17037950
TI  - The relations between personality characteristics, work environment, and the
      professional well-being of music therapists.
AB  - The purpose of this correlational study was to investigate the relations between
      professional well-being (as characterized by positive attitudes toward work and
      longevity as a practicing music therapist) and the following factors: age, level
      of education, income, attitudes regarding the workplace (e.g., perceived control,
      feeling valued, as well as the amount of perceived comfort and input into
      administrative policies), attitudes toward work as measured by the Maslach
      Burnout Inventory (Maslach & Jackson, 1986a), and measures of stress and stress
      management as measured by the Stress Profile (Nowack, 1999a). Participants
      included 49 music therapists who had between one to 36 years of work experience.
      Correlations indicated that those respondents with greatest professional
      longevity tended to have higher ratings on items regarding cognitive coping
      strategies (e.g., positive appraisal and threat minimization) and greater
      perception of personal achievement. These correlational results are related to
      psychological theories regarding occupational burnout and cognitive hardiness.

PMID- 17037951
TI  - Emotional communicability in improvised music: the case of music therapists.
AB  - Musical improvisation is considered an efficient way to express emotions in music
      therapy. We examined the ability of music therapists (MTs) to convey emotions and
      their ability to accurately decode the emotional content of musical
      improvisations. Twenty-one MTs improvised on emotions they found difficult or
      easy to express in life, using or not using an emotional imagery technique. Fifty
      five judges, some being MTs others nontherapists, evaluated the emotional content
      of the improvisations. Results showed that neither experience in therapy, nor
      musicianship or gender of the improviser were connected to emotional
      communicability (EC). Emotions that were reported as easy to express in life were
      communicated more accurately than those difficult to express in life. Emotional
      imagery did not facilitate and, to some extent, hindered emotional
      communicability. Some emotions were found to be difficult to express (e.g.,
      anger) in comparison to others (e.g., happiness). MTs decoded the emotional
      content of the improvisations more accurately than nontherapists. Implications
      for the practical musical and emotional training of music therapists are
      discussed.

PMID- 17037952
TI  - Value of musical instruments used by the therapist to elicit responses from
      individuals in various stages of Alzheimer's disease.
AB  - The purpose of this study was to determine the value of designated musical
      instruments used by the therapist to elicit responses from persons with
      Alzheimer's disease (AD) during group sessions. In Experiment 1, 15 individuals
      in the early and middle stages of AD echoed rhythm patterns played by the
      therapist via the djembe, claves, paddle drum, and maraca. Results indicated
      significance for the rhythm patterns used, p < .05, and the types of instruments
      used, p < .05. A significant difference occurred for interaction of instruments
      by rhythms, p < .001. Rhythmic accuracy was highest when the therapist presented
      rhythms on the djembe, followed by the paddle drum, maraca, and claves. The most
      accurate rhythm pattern was 8 eighth-notes, the second most accurate was 4
      quarter-notes, and the third was 2 eighths followed by a quarter note, repeated.
      Ten individuals in the middle to later stages of AD participated in Experiment 2.
      The treatment conditions consisted of 6 musical instruments used by the
      therapists to elicit responses during movement, singing, and rhythm activities.
      Average participation at any level (singing and moving/playing, singing only, and
      moving/playing only) in the 6 treatment conditions was highest during a cappella
      singing (63%), followed by djembe (61%), keyboard (60%), guitar and djembe (57%),
      and then guitar (54%) and autoharp (54%). Average participation at any level in
      the four activities, without any consideration of instruments, was as follows:
      83% for the rhythm activity, 51% for the movement activity, and 49% for the first
      as well as second singing activity. Results indicated significant differences for
      the treatment conditions, p < .001, and for types of activities, p < .05.
      Significant difference, p < .01, occurred for interaction of treatment condition
      by activity.

PMID- 17037953
TI  - Use of preferred music to reduce emotional distress and symptom activity during
      radiation therapy.
AB  - Music therapy has decreased anxiety levels in many medical settings. This
      randomized clinical trial examined the effectiveness of a music listening
      intervention, delivered by a board-certified music therapist, in patients
      undergoing curative radiation therapy (RT). Emotional distress (anxiety,
      depression, and treatment-related distress) and symptoms (fatigue and pain) were
      measured at baseline, mid-treatment, and end of treatment in 63 patients
      undergoing RT. Although patients who listened to self-selected music reported
      lower anxiety and treatment-related distress, there was a decline in these
      outcomes for patients in both groups over the course of RT. Depression, fatigue,
      and pain were not appreciably affected by music therapy. Within the music group,
      there was a significant correlation between number of times music was used/week
      and the change in treatment-related distress, suggesting that higher doses of
      music produced greater declines in distress. While these findings provided some
      support for the use of music in reducing distress during RT, further research
      demonstrating clear differences between intervention and control conditions is
      needed. Physical symptoms were not affected by the use of music over the course
      of RT.

PMID- 17037958
TI  - A polynomial-time algorithm for de novo protein backbone structure determination
      from nuclear magnetic resonance data.
AB  - We describe an efficient algorithm for protein backbone structure determination
      from solution Nuclear Magnetic Resonance (NMR) data. A key feature of our
      algorithm is that it finds the conformation and orientation of secondary
      structure elements as well as the global fold in polynomial time. This is the
      first polynomial-time algorithm for de novo high-resolution biomacromolecular
      structure determination using experimentally recorded data from either NMR
      spectroscopy or X-ray crystallography. Previous algorithmic formulations of this
      problem focused on using local distance restraints from NMR (e.g., nuclear
      Overhauser effect [NOE] restraints) to determine protein structure. This approach
      has been shown to be NP-hard, essentially due to the local nature of the
      constraints. In practice, approaches such as molecular dynamics and simulated
      annealing, which lack both combinatorial precision and guarantees on running time
      and solution quality, are used routinely for structure determination. We show
      that residual dipolar coupling (RDC) data, which gives global restraints on the
      orientation of internuclear bond vectors, can be used in conjunction with very
      sparse NOE data to obtain a polynomial-time algorithm for structure
      determination. Furthermore, an implementation of our algorithm has been applied
      to six different real biological NMR data sets recorded for three proteins. Our
      algorithm is combinatorially precise, polynomialtime, and uses much less NMR data
      to produce results that are as good or better than previous approaches in terms
      of accuracy of the computed structure as well as running time.

PMID- 17037959
TI  - Wavelet analysis of DNA walks.
AB  - A wavelet transform of the DNA "walk" constructed from a genomic sequence offers
      a direct visualization of short and long-range patterns in nucleotide sequences.
      We study sequences that encode diverse biological functions, taken from a variety
      of genomes. Pattern irregularities in the transform are frequently associated
      with sequences of biological interest. Exonic regions, for example, visualize
      differently under wavelet analysis than introns, and ribosomal RNA regions
      display distinct universal signatures. DNA walk wavelet analysis can provide a
      sensitive and rapid assessment of the putative biological significance of genomic
      DNA.

PMID- 17037960
TI  - Detecting conserved interaction patterns in biological networks.
AB  - Molecular interaction data plays an important role in understanding biological
      processes at a modular level by providing a framework for understanding cellular
      organization, functional hierarchy, and evolutionary conservation. As the quality
      and quantity of network and interaction data increases rapidly, the problem of
      effectively analyzing this data becomes significant. Graph theoretic formalisms,
      commonly used for these analysis tasks, often lead to computationally hard
      problems due to their relation to subgraph isomorphism. This paper presents an
      innovative new algorithm, MULE, for detecting frequently occurring patterns and
      modules in biological networks. Using an innovative graph simplification
      technique based on ortholog contraction, which is ideally suited to biological
      networks, our algorithm renders these problems computationally tractable and
      scalable to large numbers of networks. We show, experimentally, that our
      algorithm can extract frequently occurring patterns in metabolic pathways and
      protein interaction networks from the KEGG, DIP, and BIND databases within
      seconds. When compared to existing approaches, our graph simplification technique
      can be viewed either as a pruning heuristic, or a closely related, but
      computationally simpler task. When used as a pruning heuristic, we show that our
      technique reduces effective graph sizes significantly, accelerating existing
      techniques by several orders of magnitude! Indeed, for most of the test cases,
      existing techniques could not even be applied without our pruning step. When used
      as a stand-alone analysis technique, MULE is shown to convey significant
      biological insights at near-interactive rates. The software, sample input graphs,
      and detailed results for comprehensive analysis of nine eukaryotic PPI networks
      are available at www.cs.purdue.edu/homes/koyuturk/mule.

PMID- 17037961
TI  - Settling the intractability of multiple alignment.
AB  - Multiple alignment is a core problem in computational biology that has received
      much attention over the years, both in the line of heuristics and hardness
      results. In most expositions of the problem it is referred to as NP-hard and
      references are given to one of the available hardness results. However, previous
      to this paper not even the most elementary variation of the problem, multiple
      alignment under the unit metric, had been proved hard. The aim of this paper is
      to settle the NP-hardness of the most common variations of multiple alignment.
      The following variations are shown NP-hard for all metrics over binary or larger
      alphabets: MULTIPLE ALIGNMENT WITH SP-SCORE, STAR ALIGNMENT, and TREE ALIGNMENT
      (for a given phylogeny). In addition, NP-hardness results are provided for
      CONSENSUS PATTERNS and SUBSTRING PARSIMONY.

PMID- 17037962
TI  - On the similarity of sets of permutations and its applications to genome
      comparison.
AB  - The comparison of genomes with the same gene content relies on our ability to
      compare permutations, either by measuring how much they differ, or by measuring
      how much they are alike. With the notable exception of the breakpoint distance,
      which is based on the concept of conserved adjacencies, measures of distance do
      not generalize easily to sets of more than two permutations. In this paper, we
      present a basic unifying notion, conserved intervals, as a powerful
      generalization of adjacencies, and as a key feature of genome rearrangement
      theories. We also show that sets of conserved intervals have elegant nesting and
      chaining properties that allow the development of compact graphic
      representations, and linear time algorithms to manipulate them.

PMID- 17037963
TI  - Optimizing multiple spaced seeds for homology search.
AB  - Optimized spaced seeds improve sensitivity and specificity in local homology
      search. Several authors have shown that multiple seeds can have better
      sensitivity and specificity than single seeds. We describe a linear programming
      (LP)-based algorithm to optimize a set of seeds. Theoretically, our algorithm
      offers a performance guarantee: the sensitivity of a chosen seed set is at least
      70% of what can be achieved, in most reasonable models of homologous sequences.
      In practice, our algorithm generates a solution which is at least 90% of the
      optimal. Our method not only achieves performance better than or comparable to
      that of a greedy algorithm, but also gives this area a mathematical foundation.

PMID- 17037964
TI  - Segmenting eukaryotic genomes with the Generalized Gibbs Sampler.
AB  - Eukaryotic genomes display segmental patterns of variation in various properties,
      including GC content and degree of evolutionary conservation. DNA segmentation
      algorithms are aimed at identifying statistically significant boundaries between
      such segments. Such algorithms may provide a means of discovering new classes of
      functional elements in eukaryotic genomes. This paper presents a model and an
      algorithm for Bayesian DNA segmentation and considers the feasibility of using it
      to segment whole eukaryotic genomes. The algorithm is tested on a range of
      simulated and real DNA sequences, and the following conclusions are drawn.
      Firstly, the algorithm correctly identifies non-segmented sequence, and can thus
      be used to reject the null hypothesis of uniformity in the property of interest.
      Secondly, estimates of the number and locations of change-points produced by the
      algorithm are robust to variations in algorithm parameters and initial starting
      conditions and correspond to real features in the data. Thirdly, the algorithm is
      successfully used to segment human chromosome 1 according to GC content, thus
      demonstrating the feasibility of Bayesian segmentation of eukaryotic genomes. The
      software described in this paper is available from the author's website
      (www.uq.edu.au/ approximately uqjkeith/) or upon request to the author.

PMID- 17037965
TI  - Aligning families of two-dimensional gels by a combined multiresolution forward
      inverse transformation approach.
AB  - A new method for aligning families of two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) images arising in proteomics studies is presented.
      Forward piecewise bilinear transformations are used to determine an ideal gel and
      to obtain an initial alignment of the family of gels to this ideal gel. Both the
      ideal landmarks and the coefficients defining the transformations are obtained by
      solving a quadratic programming problem. The alignment is then improved by using
      inverse transformations on finer grids. Numerical results for a family of 123
      gels are reported.

PMID- 17037966
TI  - Evidence-based priming.

PMID- 17037967
TI  - Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived
      advanced glycation endproducts: an overview of current clinical studies,
      evidence, and limitations.
AB  - BACKGROUND: Advanced glycation endproducts (AGEs) predict long-term complications
      in agerelated diseases. However, there are no clinically applicable markers for
      measuring AGEs in vivo. METHODS: We have recently introduced the AGE-Reader
      (DiagnOptics B.V., Groningen, The Netherlands) to noninvasively measure AGE
      accumulation in the human skin of the forearm, making use of the characteristic
      autofluorescence (AF) pattern that AGEs encompass. Skin AF is calculated as a
      ratio of mean intensities detected from the skin between 420-600 nm and 300-420
      nm. It correlates with collagen-linked fluorescence and specific skin AGE levels
      from skin biopsies in diabetes, renal failure, and control subjects. Skin AF
      levels are increased in patients with diabetes and renal failure and are
      associated with the presence of vascular complications. Additionally, skin AF is
      strongly related to the progression of coronary heart disease and mortality,
      independently of traditional risk factors. Since skin pigmentation might
      influence skin AF, we have investigated the relation of relative skin reflectance
      (R%) to skin AF in subjects with varying skin phototypes (SPT). RESULTS: The data
      presented in this article suggest that only in subjects with an SPT of V and VI
      or R% <12%, no reliable measurement can be performed. Therefore, the current
      prototype of the AGE-Reader is suitable for subjects with SPT I-IV or R% >12%,
      and more research is needed for a broader application. CONCLUSION: The AGE-Reader
      is useful as a noninvasive clinical tool for assessment of risk for long-term
      vascular complications in diabetes and in other conditions associated with AGE
      accumulation.

PMID- 17037968
TI  - No differences in efficacy between noncultured and cultured islets in reducing
      hyperglycemia in a nonvascularized islet graft model.
AB  - BACKGROUND: Although islet transplantation is a promising method to restore
      normoglycemia in recipients with diabetes, large numbers of pancreatic islets are
      still needed. It has been suggested that the use of freshly isolated islets could
      improve transplantation outcome through better vascular engraftment. Using a
      technique of microencapsulation, a model where revascularization is not possible,
      we investigated the importance of revascularization for transplantation outcome.
      METHODS: Either 700 or 350 3-day-cultured or noncultured encapsulated islets were
      transplanted intraperitoneally into syngeneic mice with alloxan-induced diabetes.
      In addition, 700 nonencapsulated islets were transplanted to mice with diabetes.
      Blood glucose concentrations were monitored, and glucose tolerance tests were
      carried out. After 42 days, the encapsulated islets were retrieved and assayed
      for glucose oxidation and insulin release rates. RESULTS: There were no
      differences between capsules containing fresh or cultured islets in their
      capacity to lower the blood glucose concentration of the recipients or in the in
      vitro function after capsule retrieval. Interestingly, mice that were
      intraperitoneally transplanted with 700 encapsulated islets had average blood
      glucose levels well below 11 mM for most of the study, whereas the same number of
      nonencapsulated islets had no beneficial effects on the blood glucose
      homeostasis. CONCLUSIONS: Encapsulated islets can reverse hyperglycemia after
      transplantation to the intraperitoneal site. This effect was not seen when
      nonencapsulated islets were grafted. Since a 3- day culture period did not
      influence the outcome of transplantation of encapsulated islets there is evidence
      to suggest that a more appropriate revascularization may explain why freshly
      isolated islets are more efficient than cultured islets.

PMID- 17037969
TI  - Biocompatibility of an enzyme-based, electrochemical glucose sensor for short
      term implantation in the subcutis.
AB  - BACKGROUND: Continuous glucose measurements provide improved glycemic control and
      may prevent hypoglycemia and long-term complications of diabetes. One of the most
      promising techniques is the short-term implantation of electrochemical glucose
      sensors in subcutis. However, the inflammatory reaction to these sensors may lead
      to bioinstability of sensor measurements. The purpose of the present
      investigation was to examine factors contributing to the observed subcutaneous
      inflammatory reaction to an enzyme-based electrochemical glucose sensor for
      continuous glucose measurements. The sensor biocompatibility was assessed in
      vitro and in vivo. METHODS: A toxicological assessment was performed on sensor
      materials and leachables, and the endotoxin content of sensors was determined by
      a Limulus amoebocyte lysate (LAL) test. Moreover, as a consequence of permanent
      penetration of the skin by the sensor the role of bacterial migration to the
      tissue was investigated. In vivo biocompatibility was investigated through
      histological examination of implanted sensor membranes for 3 days in pigs.
      Additionally, the effect of needle size and type (normal vs. inserter needle) on
      tissue trauma at sensor insertion was evaluated, and the healing of subcutis was
      assessed histologically from 3 to 14 days after removal of sensors. RESULTS: The
      toxicological assessment and the LAL test showed no concerns in a 3-day
      implantation scenario, and bacterial migration to the subcutis could not be
      detected. The histological examination showed that a reduction in needle size
      reduced the extent of inflammation to very low levels, and that the different
      sensor membranes showed similar extent and type of inflammation. Additionally,
      the extent of subcutaneous tissue reaction after removal of sensors declined
      gradually over time and returned to near-normal levels after 2 weeks. CONCLUSION:
      The electrochemical enzyme-based glucose sensor for continuous glucose
      measurements in subcutis is acceptable from a biocompatibility point of view.
      Reducing the inserter needle in size reduces the trauma induced at sensor
      implantation to neglible levels. Furthermore, the tissue reaction to the sensor
      returns to near-normal 2 weeks after the sensor has been removed following a 3
      day implantation period.

PMID- 17037970
TI  - "Glucometrics"--assessing the quality of inpatient glucose management.
AB  - BACKGROUND: For patients with diabetes, the quality of outpatient glycemic
      control is readily assessed by hemoglobin A1c. In contrast, standardized measures
      for assessing the quality of blood glucose (BG) management in hospitalized
      patients are lacking. Because of recent studies demonstrating the benefits of
      strict glycemic control in critically ill patients, hospitals nationwide are
      dedicating resources to address this important issue. To facilitate advances in
      this nascent field, standardized metrics for inpatient glycemic control should be
      developed and validated. METHODS: We used 1 month of fingerstick BG levels from a
      general hospital ward to develop and test three analytic models, based on three
      units of inpatient BG analysis: population (i.e., ward), patient-day, and
      patient. To assess the effect of the source of blood samples, we repeated these
      analyses after adding venous plasma glucose levels. Finally, we employed an
      idealized intensive care unit data set to establish "gold standard" metrics for
      inpatient glycemic control. RESULTS: Mean and median BG levels and the proportion
      of BG levels within an "optimal" range (80-139 mg/dL) were similar among the
      three models, whereas hypoglycemic and hyperglycemic event rates varied
      considerably. Inclusion of venous glucose levels did not substantially affect the
      results. Of the three models tested, the patient-day model appears to most
      faithfully reflect the quality of inpatient glycemic control. Achieving 85% of BG
      levels within optimal range may be considered gold standard. CONCLUSIONS: If
      validated elsewhere, these "glucometrics" would permit objective comparisons of
      inpatient glycemic control among hospitals and patient care units, and would
      allow institutions to gauge the success of their quality improvement initiatives.

PMID- 17037971
TI  - Microdialysis-based 48-hour continuous glucose monitoring with GlucoDay: clinical
      performance and patients' acceptance.
AB  - BACKGROUND: This study was designed to assess clinical performance and patients'
      acceptance of the minimally invasive microdialysis-based continuous glucose
      monitoring system Gluco- Day() (Menarini Diagnostics, Florence, Italy) with a
      targeted monitoring time of 48 h. METHODS: An inpatient sample of 28 patients
      with diabetes was studied. The analysis of clinical performance was performed
      using mean absolute differences (MAD) (in percent), Pearson correlations, the
      Bland-Altman analysis, and Clarke Error Grid Analysis (EGA). GlucoDay glucose
      values were compared with laboratory standard blood glucose measurements
      (glucohexokinase assay). The patients' acceptance of the monitoring device was
      assessed via two self-report scales (pain during application and discomfort while
      wearing device). RESULTS: A mean (+/- SD) monitoring time of 45.7 +/- 3.3 h with
      a total of 484 paired readings could be achieved. A correlation of r (average) =
      0.91 and a MAD of 19.9% indicated satisfactory to good clinical performance. Of
      the paired readings, 95.5% fell into the acceptable A and B zones of the EGA.
      Rather wide 95% limits of agreement were revealed in the Bland-Altman analysis.
      Whereas virtually no pain was experienced during sensor application, discomfort
      associated with wearing the device was rather high. All of the participants,
      however, stated that they would wear the device again. CONCLUSIONS: Satisfactory
      to good performance of the GlucoDay monitor was observed, indicating the device
      to be suitable for routine clinical use. In particular, however, the discomfort
      experienced during wearing requires further improvements in its usability.

PMID- 17037973
TI  - Diabetes information systems: a rapidly emerging support for diabetes
      surveillance and care.
AB  - BACKGROUND: With the rapid advances in information technology in the last decade,
      various diabetes information systems have evolved in different parts of the
      world. Availability of new technologies and information systems for monitoring
      and treating diabetes is critical to achieving recommended metabolic control,
      including glycosylated hemoglobin levels. The first step is to develop a
      registry, including a patient identifier that can link multiple data sources,
      which can then serve as a springboard to electronic mechanisms for practitioners
      to gain information on performance and results. OBJECTIVE: The aim is to review
      the provisions for diabetes surveillance in different parts of the world. This is
      a systematic review of national and regional information systems for diabetes
      surveillance. LITERATURE REVIEW: A comprehensive review was undertaken using
      Medline literature review, internet search using the Google search engine, and e
      mail consultation with opinion leaders. TOPICS REVIEW: National/regional-level
      diabetes surveillance systems in Europe, the United States, Australia/New
      Zealand, and Asia have been reviewed. State-of-the-art diabetes information
      systems linking multiple data sources, with extensive audit and feedback
      capabilities, have also been looked at. RESULTS: National/regional-level audit
      databases have been tabulated. Diabetes information systems linking multiple data
      sources have been described. Most of the developed countries have now implemented
      systems such as diabetes registers and audits for diabetes surveillance in at
      least some regions, if not nationally. Developing nations are beginning to
      recognize the need for chronic disease management. CONCLUSIONS: With the
      advancements in information technology, the diabetes registers have the potential
      to rise beyond their traditional functions with dynamic data integration,
      decision support, and data access, as demonstrated by some diabetes information
      systems. With the rapid pace of development in electronic health records and
      health information systems, countries that are beginning to build their health
      information technology infrastructure could benefit from planning and funding
      along these lines.

PMID- 17037972
TI  - Design and implementation of a web-based patient portal linked to an ambulatory
      care electronic health record: patient gateway for diabetes collaborative care.
AB  - BACKGROUND: Despite the availability of expert guidelines and widespread diabetes
      quality improvement efforts, care of patients with diabetes remains suboptimal.
      Two key barriers to care that may be amenable to informatics-based interventions
      include (1) lack of patient engagement with therapeutic care plans and (2) lack
      of medication adjustment by physicians ("clinical inertia") during clinical
      encounters. METHODS: The authors describe the conceptual framework, design,
      implementation, and analysis plan for a diabetes patient web-portal linked
      directly to the electronic health record (EHR) of a large academic medical center
      via secure Internet access designed to overcome barriers to effective diabetes
      care. RESULTS: Partners HealthCare System (Boston, MA), a multi-hospital health
      care network comprising several thousand physicians caring for over 1 million
      individual patients, has developed a comprehensive patient web-portal called
      Patient Gateway that allows patients to interact directly with their EHR via
      secure Internet access. Using this portal, a specific diabetes interface was
      designed to maximize patient engagement by importing the patient's current
      clinical data in an educational format, providing patient-tailored decision
      support, and enabling the patient to author a "Diabetes Care Plan." The physician
      view of the patient's Diabetes Care Plan was designed to be concise and to fit
      into typical EHR clinical workflow. CONCLUSIONS: We successfully designed and
      implemented a Diabetes Patient portal that allows direct interaction with our
      system's EHR. We are assessing the impact of this advanced informatics tool for
      collaborative diabetes care in a clinic-randomized controlled trial among 14
      primary care practices within our integrated health care system.

PMID- 17037974
TI  - "Waste not, want not": determining the optimal priming volume for intravenous
      insulin infusions.
AB  - BACKGROUND: Insulin adsorbs to plastics used for intravenous (IV) tubing. As a
      result, clinical IV insulin infusion procotols advise an initial priming volume
      of up to 50 mL, which may be wasteful-especially since most institutions use 100
      mL IV solution bags. In this brief report, we sought to determine the optimal
      priming volume required for clinical IV insulin infusions. METHODS: One hundred
      units of regular human insulin was dissolved into 100 mL of 0.9% NaCl. Employing
      a standard polypropylene infusion set, a priming infusion was started. At 10- mL
      intervals, from 0 to 50 mL, effluent was collected directly into glass vials.
      After dilution (1:10,000) using a proprietary buffer, insulin concentrations were
      then measured using a double antibody radioimmunoassay. Twenty individually
      prepared insulin bags were tested in this manner. RESULTS: Insulin levels without
      prime were 15.8% [95% confidence interval (CI), 9.1-22.6%] lower than insulin
      levels following 50 mL of prime (designated as "maximal values"). After a priming
      volume of 10 mL, insulin adsorption losses fell to a marginally significant 6.6%
      (95% CI, 0.1-13.1%). Following 20 mL of prime, insulin concentrations were
      indistinguishable from maximal values (3.4% loss, 95% CI, -0.2% to 7.1%).
      CONCLUSIONS: For standard IV insulin infusions, a priming volume of 20 mL is
      sufficient to minimize the effect of insulin adsorption losses to IV lines.
      Priming volumes exceeding 20 mL are wasteful, increase costs, and generate
      unnecessary work for nurses and pharmacists.

PMID- 17037976
TI  - The multiple endocrine neoplasia syndromes.
AB  - Multiple endocrine neoplasia (MEN) type 1 and type 2 exhibit an autosomal
      dominant pattern of inheritance. In the past two decades the germline mutations
      that cause these inherited syndromes have been identified. The large majority of
      patients with MEN1 have mutations in the menin gene. Mutations in the REarranged
      during Transfection (RET) gene cause MEN2A, MEN2B, and familial medullary thyroid
      carcinoma (FMTC). Specific codon mutations within RET correlate with disease
      phenotype and severity. Also, children from families with MEN2A, MEN2B, or FMTC,
      who are found to have inherited a mutated RET allele, can be managed by
      prophylactic thyroidectomy, thus preventing the development of medullary thyroid
      carcinoma (MTC), the dominant endocrinopathy in patients with these hereditary
      syndromes. New insights into the molecular pathway of RET signal transduction are
      leading to novel targeted therapies in patients with locally advanced or
      metastatic hereditary MTC.

PMID- 17037977
TI  - Stochastic simulation of chemical kinetics.
AB  - Stochastic chemical kinetics describes the time evolution of a well-stirred
      chemically reacting system in a way that takes into account the fact that
      molecules come in whole numbers and exhibit some degree of randomness in their
      dynamical behavior. Researchers are increasingly using this approach to chemical
      kinetics in the analysis of cellular systems in biology, where the small
      molecular populations of only a few reactant species can lead to deviations from
      the predictions of the deterministic differential equations of classical chemical
      kinetics. After reviewing the supporting theory of stochastic chemical kinetics,
      I discuss some recent advances in methods for using that theory to make numerical
      simulations. These include improvements to the exact stochastic simulation
      algorithm (SSA) and the approximate explicit tau-leaping procedure, as well as
      the development of two approximate strategies for simulating systems that are
      dynamically stiff: implicit tau-leaping and the slow-scale SSA.

PMID- 17037978
TI  - Regulation of receptor trafficking by GRKs and arrestins.
AB  - To ensure that extracellular stimuli are translated into intracellular signals of
      appropriate magnitude and specificity, most signaling cascades are tightly
      regulated. One of the major mechanisms involved in the regulation of G protein
      coupled receptors (GPCRs) involves their endocytic trafficking. GPCR endocytic
      trafficking entails the targeting of receptors to discrete endocytic sites at the
      plasma membrane, followed by receptor internalization and intracellular sorting.
      This regulates the level of cell surface receptors, the sorting of receptors to
      degradative or recycling pathways, and in some cases the specific signaling
      pathways. In this chapter we discuss the mechanisms that regulate receptor
      endocytic trafficking, emphasizing the role of GPCR kinases (GRKs) and arrestins
      in this process.

PMID- 17037979
TI  - Integration of rapid signaling events with steroid hormone receptor action in
      breast and prostate cancer.
AB  - Steroid hormone receptors (SRs) are ligand-activated transcription factors and
      sensors for growth factor-initiated signaling pathways in hormonally regulated
      tissues, such as the breast or prostate. Recent discoveries suggest that several
      protein kinases are rapidly activated in response to steroid hormone binding to
      cytoplasmic SRs. Induction of rapid signaling upon SR ligand binding ensures that
      receptors and coregulators are appropriately phosphorylated as part of optimal
      transcription complexes. Alternatively, SR-activated kinase cascades provide
      additional avenues for SR-regulated gene expression independent of SR nuclear
      action. We provide an overview of SR and signaling cross talk in breast and
      prostate cancers, using the human progesterone receptor (PR) and androgen
      receptor (AR) as models. Kinases are emerging as key mediators of SR action.
      Cross talk between SR and membrane-initiated signaling events suggests a
      mechanism for coordinate regulation of gene subsets by mitogenic stimuli in
      hormonally responsive normal tissues; such cross talk is suspected to contribute
      to cancer biology.

PMID- 17037980
TI  - Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen
      availability.
AB  - The ability of fishes, amphibians, and reptiles to survive extremes of oxygen
      availability derives from a core triad of adaptations: profound metabolic
      suppression, tolerance of ionic and pH disturbances, and mechanisms for avoiding
      free-radical injury during reoxygenation. For long-term anoxic survival, enhanced
      storage of glycogen in critical tissues is also necessary. The diversity of body
      morphologies and habitats and the utilization of dormancy have resulted in a
      broad array of adaptations to hypoxia in lower vertebrates. For example, the most
      anoxia-tolerant vertebrates, painted turtles and crucian carp, meet the challenge
      of variable oxygen in fundamentally different ways: Turtles undergo near
      suspended animation, whereas carp remain active and responsive in the absence of
      oxygen. Although the mechanisms of survival in both of these cases include large
      stores of glycogen and drastically decreased metabolism, other mechanisms, such
      as regulation of ion channels in excitable membranes, are apparently divergent.
      Common themes in the regulatory adjustments to hypoxia involve control of
      metabolism and ion channel conductance by protein phosphorylation. Tolerance of
      decreased energy charge and accumulating anaerobic end products as well as
      enhanced antioxidant defenses and regenerative capacities are also key to hypoxia
      survival in lower vertebrates.

PMID- 17037981
TI  - Hypoxia tolerance in mammals and birds: from the wilderness to the clinic.
AB  - All mammals and birds must develop effective strategies to cope with reduced
      oxygen availability. These animals achieve tolerance to acute and chronic hypoxia
      by (a) reductions in metabolism, (b) the prevention of cellular injury, and (c)
      the maintenance of functional integrity. Failure to meet any one of these tasks
      is detrimental. Birds and mammals accomplish this triple task through a highly
      coordinated, systems-level reconfiguration involving the partial shutdown of some
      but not all organs. This reconfiguration is achieved through a similarly complex
      reconfiguration at the cellular and molecular levels. Reconfiguration at these
      various levels depends on numerous factors that include the environment, the
      degree of hypoxic stress, and developmental, behavioral, and ecological
      conditions. Although common molecular strategies exist, the cellular and
      molecular changes in any given cell are very diverse. Some cells remain
      metabolically active, whereas others shut down or rely on anaerobic metabolism.
      This cellular shutdown is temporarily regulated, and during hypoxic exposure,
      active cellular networks must continue to control vital functions. The challenge
      for future research is to explore the cellular mechanisms and conditions that
      transform an organ or a cellular network into a hypometabolic state, without loss
      of functional integrity. Much can be learned in this respect from nature: Diving,
      burrowing, and hibernating animals living in diverse environments are masters of
      adaptation and can teach us how to deal with hypoxia, an issue of great clinical
      significance.

PMID- 17037982
TI  - The centaurin gamma-1 GTPase-like domain functions as an NTPase.
AB  - Centaurins are a family of proteins that contain GTPase-activating protein
      domains, with the gamma family members containing in addition a GTPase-like
      domain. Centaurins reside mainly in the nucleus and are known to activate
      phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and
      vesicular trafficking. In the present study, using X-ray structural analysis,
      enzymatic assays and nucleotide-binding studies, we show that, for CENTG1
      (centaurin gamma-1) the GTPase-like domain has broader trinucleotide specificity.
      Alterations within the G4 motif of CENTG1 from the highly conserved NKXD found in
      typical GTPases to TQDR result in the loss of specificity, a lower affinity for
      the nucleotides and higher turnover rates. These results indicate that the
      centaurins could be more accurately classified as NTPases and point to
      alternative mechanisms of cell signalling control.

PMID- 17037983
TI  - Regulation of the human mucin MUC4 by taurodeoxycholic and taurochenodeoxycholic
      bile acids in oesophageal cancer cells is mediated by hepatocyte nuclear factor
      1alpha.
AB  - MUC4 (mucin 4) is a membrane-bound mucin overexpressed in the early steps of
      oesophageal carcinogenesis and implicated in tumour progression. We previously
      showed that bile acids, main components of gastro-oesophageal reflux and tumour
      promoters, up-regulate MUC4 expression [Mariette, Perrais, Leteurtre, Jonckheere,
      Hemon, Pigny, Batra, Aubert, Triboulet and Van Seuningen (2004) Biochem. J. 377,
      701-708]. HNF (hepatocyte nuclear factor) 1alpha and HNF4alpha transcription
      factors are known to mediate bile acid effects, and we previously identified cis
      elements for these factors in MUC4 distal promoter. Our aim was to demonstrate
      that these two transcription factors were directly involved in MUC4 activation by
      bile acids. MUC4, HNF1alpha and HNF4alpha expressions were evaluated by
      immunohistochemistry in human oesophageal tissues. Our results indicate that
      MUC4, HNF1alpha and HNF4alpha were co-expressed in oesophageal metaplastic and
      adenocarcinomatous tissues. Studies at the mRNA, promoter and protein levels
      indicated that HNF1alpha regulates endogenous MUC4 expression by binding to two
      cognate cis-elements respectively located at -3332/-3327 and -3040/-3028 in the
      distal promoter. We also showed by siRNA (small interfering RNA) approach, co
      transfection and site-directed mutagenesis that HNF1alpha mediates
      taurodeoxycholic and taurochenodeoxycholic bile acid activation of endogenous
      MUC4 expression and transcription in a dose-dependent manner. In conclusion,
      these results describe a new mechanism of regulation of MUC4 expression by bile
      acids, in which HNF1alpha is a key mediator. These results bring new insights
      into MUC4 up-regulation in oesophageal carcinoma associated with bile reflux.

PMID- 17037984
TI  - Biosynthesis of the dystonia-associated AAA+ ATPase torsinA at the endoplasmic
      reticulum.
AB  - TorsinA is a widely expressed AAA(+) (ATPases associated with various cellular
      activities) ATPase of unknown function. Previous studies have described torsinA
      as a type II protein with a cleavable signal sequence, a single membrane spanning
      domain, and its C-terminus located in the ER (endoplasmic reticulum) lumen.
      However, in the present study we show that torsinA is not in fact an integral
      membrane protein. Instead we find that the mature protein associates peripherally
      with the ER membrane, most likely through an interaction with an integral
      membrane protein. Consistent with this model, we provide evidence that the signal
      peptidase complex cleaves the signal sequence of torsinA, and we show that the
      region previously suggested to form a transmembrane domain is translocated into
      the lumen of the ER. The finding that torsinA is a peripheral, and not an
      integral membrane protein as previously thought, has important implications for
      understanding the function of this novel ATPase.

PMID- 17037985
TI  - An active site tyrosine residue is essential for amidohydrolase but not for
      esterase activity of a class 2 histone deacetylase-like bacterial enzyme.
AB  - HDACs (histone deacetylases) are considered to be among the most important
      enzymes that regulate gene expression in eukaryotic cells acting through
      deacetylation of epsilon-acetyl-lysine residues within the N-terminal tail of
      core histones. In addition, both eukaryotic HDACs as well as their bacterial
      counterparts were reported to also act on non-histone targets. However, we are
      still far from a comprehensive understanding of the biological activities of this
      ancient class of enzymes. In the present paper, we studied in more detail the
      esterase activity of HDACs, focussing on the HDAH (histone deacetylase-like
      amidohydrolase) from Bordetella/Alcaligenes strain FB188. This enzyme was
      classified as a class 2 HDAC based on sequence comparison as well as functional
      data. Using chromogenic and fluorogenic ester substrates we show that HDACs such
      as FB188 HDAH indeed have esterase activity that is comparable with those of
      known esterases. Similar results were obtained for human HDAC1, 3 and 8. Standard
      HDAC inhibitors were able to block both activities with similar IC(50) values.
      Interestingly, HDAC inhibitors such as suberoylanilide hydroxamic acid (SAHA)
      also showed inhibitory activity against porcine liver esterase and Pseudomonas
      fluorescens lipase. The esterase and the amidohydrolase activity of FB188 HDAH
      both appear to have the same substrate specificity concerning the acyl moiety.
      Interestingly, a Y312F mutation in the active site of HDAH obstructed
      amidohydrolase activity but significantly improved esterase activity, indicating
      subtle differences in the mechanism of both catalytic activities. Our results
      suggest that, in principle, HDACs may have other biological roles besides acting
      as protein deacetylases. Furthermore, data on HDAC inhibitors affecting known
      esterases indicate that these molecules, which are currently among the most
      promising drug candidates in cancer therapy, may have a broader target profile
      requiring further exploration.

PMID- 17037987
TI  - Psychological factors affect the frequency of belching in patients with
      aerophagia.
AB  - BACKGROUND: In patients with aerophagia and excessive belching an organic cause
      is seldom found and a psychogenic cause is often suspected. AIM: To investigate
      the effects of attention and distraction on the frequency of belching in patients
      with aerophagia. METHODS: In 10 patients with aerophagia, combined esophageal
      manometry and impedance monitoring was performed for 2 h, consisting of four 30
      minute recording periods. Period I: patient unaware that recording had commenced.
      Period II: patient informed of recording in progress. Period III: distraction by
      filling in questionnaires. Period IV: no distraction. RESULTS: A total of 1,258
      belches was measured, 51 of which were the result of air that escaped from the
      stomach (gastric belches). A total of 1,207 belches (96%) were events during
      which air was expelled in the oral direction almost immediately after entering
      the esophagus from there (supragastric belches). Gastric belches were distributed
      equally over the first (1.5 [0.5-2.0]), second (1.5 [0.5-2.0]), third (1.0 [0
      2.0]), and fourth (1.0 [0-2.0]) recording periods. In contrast, the incidence of
      supragastric belches increased significantly from 0 (0-32) in period I to 30 (18
      60) in period II, after patients were told that recording was started. During
      period III (questionnaires) the incidence of supragastric belches decreased to 14
      (4-30). In period IV the incidence of supragastric belches increased to 21 (10
      49). CONCLUSIONS: When patients with excessive belching are unaware that they are
      being studied or when they are distracted, the incidence of belching is
      significantly reduced. These findings underline the importance of psychological
      factors and provide rationale for behavioral therapy.

PMID- 17037986
TI  - Domains 16 and 17 of tropoelastin in elastic fibre formation.
AB  - Naturally occurring mutations are useful in identifying domains that are
      important for protein function. We studied a mutation in the elastin gene, 800
      3G>C, a common disease allele for SVAS (supravalvular aortic stenosis). We showed
      in primary skin fibroblasts from two different SVAS families that this mutation
      causes skipping of exons 16-17 and results in a stable mRNA. Tropoelastin lacking
      domains 16-17 (Delta16-17) was synthesized efficiently and secreted by
      transfected retinal pigment epithelium cells, but showed the deficient deposition
      into the extracellular matrix compared with normal as demonstrated by
      immunofluorescent staining and desmosine assays. Solid-phase binding assays
      indicated normal molecular interaction of Delta16-17 with fibrillin-1 and fibulin
      5. However, self-association of Delta16-17 was diminished as shown by an elevated
      coacervation temperature. Moreover, negative staining electron microscopy
      confirmed that Delta16-17 was deficient in forming fibrillar polymers. Domain 16
      has high homology with domain 30, which can form a beta-sheet structure
      facilitating fibre formation. Taken together, we conclude that domains 16-17 are
      important for self-association of tropoelastin and elastic fibre formation. This
      study is the first to discover that domains of elastin play an essential role in
      elastic fibre formation by facilitating homotypic interactions.

PMID- 17037988
TI  - Should patients with anemia and low normal or normal serum ferritin undergo
      colonoscopy?
AB  - BACKGROUND: Patients with unexplained iron deficiency anemia have a greater
      prevalence of colonic neoplasia, and should be evaluated for a colonoscopy. The
      approach to patients with anemia without iron deficiency remains unclear.
      OBJECTIVE: To compare the prevalence of colonic neoplasia in anemic patients with
      normal ferritin (>50 ng/mL), to those with ferritin < or =50 ng/mL, and nonanemic
      individuals. METHODS: Patients referred for colonoscopy for anemia evaluation
      were stratified into 3 groups: ferritin < or =50 ng/mL, 51-100 ng/mL, and >100
      ng/mL. We compared these groups to each other, and to asymptomatic nonanemic
      individuals undergoing screening colonoscopy. The prevalence of advanced colonic
      neoplasia was determined for each group using existing records. RESULTS: During
      the study period, 414 patients who underwent colonoscopy for anemia evaluation
      and 323 nonanemic individuals who underwent colonoscopy for cancer screening met
      inclusion criteria. Study subjects were mostly men. The prevalence of advanced
      colonic neoplasia in subjects with ferritin 51-100 ng/mL was 7.2% (95% CI 2.4
      17.9%), similar to 7.9% (95% CI 5.1-11.9%) in those with ferritin < or =50 ng/mL.
      The incidence of advanced colonic neoplasia in subjects with ferritin >100 ng/mL
      was 1.7% (95% CI 0.1-6.6%), similar to 1.2% (95% CI 0.4-3.3%) in the asymptomatic
      nonanemic group. After adjusting for age, patients with ferritin < or =50 ng/mL
      and 51-100 ng/mL were almost 5 times more likely to harbor advanced colonic
      neoplasia than the other groups. The addition of other laboratory parameters did
      not improve the predictive value of ferritin. CONCLUSION: A ferritin cutoff of
      100 ng/mL can be used to determine the need for colonoscopy in men with anemia.

PMID- 17037989
TI  - Biliary manifestation of Erdheim-Chester disease mimicking Klatskin's carcinoma.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis,
      characterized by infiltration of foamy, lipid-laden histiocytes often affecting
      the lower extremities and resulting in symmetrical osteosclerosis. Internal
      organs involved include the lung and the kidneys, reflecting progressive
      disseminated granulomatous infiltration. Progression may be fatal, especially in
      cases of systemic extraosseous involvement. Here, we report a patient with
      elevated serum levels of liver enzymes due to intra- and extrahepatic bile duct
      stenoses. The patient's past medical history was remarkable for ECD, since 1 yr
      before he had undergone surgery for a pituitary lesion in our neurosurgical
      department revealing the typical histological and immunohistochemical criteria of
      ECD. Because no biliary manifestation of ECD had been described so far in the
      literature, surgery of suspected bile duct carcinoma was performed unraveling an
      unresectable tumor of the hilar region. Surprisingly, histologic examination of
      intraoperative biopsy specimens failed to demonstrate malignancy but rather
      revealed another xanthogranulomatous lesion embedded in extended periductal
      fibrosis as is typically described in extrahepatic parenchymal organ
      manifestation of ECD. Other possible reasons for cholestatic liver disease were
      excluded. Secondary cholestasis was overcome by endoscopic dilatation and biliary
      stenting with stents being exchanged every 3 months. During follow-up for 7 yr we
      have observed only a slight increase of the hilar stenosis so far. This is the
      first report describing biliary manifestation of ECD. Even though ECD is a rare
      cause of cholestasis, it should be considered in patients with this disorder in
      the setting of multiorgan manifestation.

PMID- 17037990
TI  - Familial aggregation in constipated subjects in a tertiary referral center.
AB  - OBJECTIVES: Clinical observation showed that there is family aggregation in
      constipated subjects, but formal data are lacking. This prompted us to conduct a
      formal family study in constipated subjects. METHODS: Constipated subjects
      (probands) were identified according to the Rome II and Chinese constipation
      questionnaire criteria, healthy subjects were chosen as controls. Living first
      degree relatives (parents, siblings, and children) and spouses (as internal
      controls) from both groups were identified. The questionnaire on Rome II criteria
      was given to the relatives either through the index subjects or by mail. The
      questionnaire was received by mailing back or through the index subjects. Any
      nonresponders were chased. RESULTS: There were 132 probands with constipation and
      114 controls. The Rome II questionnaire was sent to a total of 677 relatives of
      the probands and 591 of the controls. Relatives were comparable in mean age, sex
      distribution, family size, and marital status in the two groups. Constipation
      prevalence was 16.4% in probands' relatives versus 9.1% in controls' relatives,
      i.e., 13% in the relatives from both proband and controls. Among the constipated
      relatives, 6.3%versus 9.3% of the relatives were spouses of the probands and
      controls (P = 0.5). Subjects with more family members having constipation will
      have higher risk of constipation: OR 2.02, CI 1.14-3.65, P = 0.0177 for at least
      one family member; OR 3.99, CI 1.86-9.23, P = 0.0006 for at least two family
      members. CONCLUSIONS: Familial aggregation of constipation occurs, supporting a
      genetic or intrafamilial environment component.

PMID- 17037991
TI  - Acute appendicitis due to appendiceal obstruction from a migrated biliary stent.
AB  - Endoscopic plastic biliary stenting is a common procedure in the management of
      benign biliary pathology. Complications from biliary stenting are rare, with
      stent occlusion being the most common. Another late complication of long-term
      biliary stenting is stent migration, which occasionally can result in bowel
      perforation and obstruction. We report an extremely unusual complication of acute
      appendicitis due to appendiceal orifice obstruction from a migrated biliary
      stent. The condition was suspected from the history in association with the
      radiological findings and was successfully treated nonoperatively with endoscopic
      stent removal.

PMID- 17037992
TI  - Incidence of arterial injuries detected by arteriography following percutaneous
      right-lobe ultrasound-guided core liver biopsies in human subjects.
AB  - PURPOSE: To determine the incidence and significance of arterial injuries
      detected by angiography subsequent to ultrasound-guided random core liver
      biopsies in normal healthy adults. MATERIALS AND METHODS: Retrospective analysis
      of 55 potential living related liver donors who underwent an ultrasound-guided
      random liver biopsy and a visceral angiogram was performed (January, 1999 to May,
      2002). All liver biopsy samples (obtained by 2-3 18-gauge needle passes) were re
      evaluated prospectively by a transplant pathologist for adequacy (defined: >or=5
      complete portal triads). Subjects who underwent angiograms before the biopsy or
      >7 days after the biopsy were excluded from the arterial injury evaluation.
      Angiograms were reviewed by two angiographers. Arterial injuries were identified
      and classified by consensus into contusions, active bleeding, arterial-venous
      fistulae, and pseudoaneurysms. RESULTS: Mean needle pass was 2.1. No major
      complications were encountered. All samples were deemed pathologically adequate.
      Forty-eight potential donors were included for the arterial injury evaluation.
      Three arterial injuries (two arterioportal fistulae, 4.2%) were found in 48
      angiograms (6.3%). None of the three injuries required intervention. CONCLUSION:
      The incidence of arterioportal fistulae following core liver biopsies has not
      changed over the past three decades despite improvement in biopsy needle
      technology, reduction of needle caliber, and the use of image guidance.

PMID- 17037993
TI  - Characterization, outcome, and prognosis in 273 patients with primary sclerosing
      cholangitis: A single center study.
AB  - OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver
      disease with varying severity and progression. This study describes the natural
      history of PSC patients and evaluates the prognostic significance of clinical,
      biochemical, and cholangiographic findings constructing a novel prognostic model.
      METHODS: A population of 273 German PSC patients was studied with a median follow
      up time of 76 months (range 1-280 months). Survival curves were analyzed by the
      Kaplan-Meier method, and prognostic significance of clinical, biochemical, and
      cholangiographic features recorded at the time of diagnosis was evaluated by
      multivariate analysis using Cox proportional-hazards regression models. RESULTS:
      The estimated median survival from the time of diagnosis to death or time of
      liver transplantation was 9.6 yr. One hundred eight (39.6%) patients underwent
      liver transplantation. Hepatobiliary malignancies were found in 39 (14.3%)
      patients of the entire PSC population. Age, low albumin, persistent bilirubin
      elevation longer than 3 months, hepatomegaly, splenomegaly, dominant bile duct
      stenosis, and intra- and extrahepatic ductal changes at the time of diagnosis
      were found to be independent risk factors correlating with poor prognosis and
      were used to construct a new prognostic model. CONCLUSIONS: A persistent
      bilirubin elevation for longer than 3 months from the time of diagnosis could be
      identified as a novel marker correlating with a poor outcome. A new prognostic
      model was developed to predict progression of PSC, which may be useful in timing
      of liver transplantation.

PMID- 17037994
TI  - Survival after colorectal cancer in patients with Crohn's disease: A nationwide
      population-based Danish follow-up study.
AB  - BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are at increased risk of
      colorectal cancer (CRC), but little is known about the impact of CD on CRC
      prognosis. Based on nationwide population-based registries, we compared survival
      among CRC patients with CD and CRC patients without CD. METHODS: We used the
      Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all
      patients diagnosed with CRC, with and without CD, in Denmark between 1977 and
      1999. We ascertained the stage distribution at the time of CRC diagnosis and 1-
      and 5-yr survival both for patients with Crohn-associated CRC and patients with
      non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting
      for gender, age, calendar year, and stage. RESULTS: We identified 100 CRC
      patients with CD and 71,438 CRC patients without CD. At the time of diagnosis,
      patients with CD were younger, but stage distributions were similar in the two
      groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95%
      CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of
      follow-up. Subanalyses showed that the effect of CD on CRC survival was more
      pronounced in the youngest patients (0-59 yr), in men, and in patients whose
      tumors had regional spread. CONCLUSIONS: We found that CD worsens the prognosis
      of CRC, particularly CRC with regional spread.

PMID- 17037995
TI  - Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The role of proton pump inhibitors (PPIs) in suspected GERD-related
      chronic laryngitis (CL) is controversial. Hence, we performed a meta-analysis of
      the existing randomized controlled trials (RCTs) to evaluate the efficacy of PPIs
      in this disorder. METHODS: Data extracted from MEDLINE (1966 to August 2005),
      Cochrane Controlled Trials Register (1997 to August 2005), EMBASE (1980 to August
      2005), ClinicalTrials.gov website, and meetings presentations (1999-2005).
      Published and unpublished randomized placebo-controlled trials of PPIs in
      suspected GERD-related CL were selected by consensus. Random effects model was
      utilized with standard approaches to quality assessment, sensitivity analysis,
      and an exploration of heterogeneity and publication bias. The primary outcome
      measure was defined as the proportion of patients with >or=50% reduction in self
      reported laryngeal symptoms. RESULTS: Pooled data from 8 studies (N = 344, PPI
      195, placebo 149; mean age 51 yr; males 55%; study duration 8-16 wk) were
      analyzed. No significant quantitative heterogeneity was found among the studies
      (chi2= 11.22, P= 0.13). Overall, PPI therapy resulted in a nonsignificant symptom
      reduction compared to placebo (relative risk 1.28, 95% confidence interval 0.94
      1.74). No clinical predictors of PPI response were identified on meta-regression
      analysis done at study level. CONCLUSIONS: PPI therapy may offer a modest, but
      nonsignificant, clinical benefit over placebo in suspected GERD-related CL.
      Validated diagnostic guidelines may facilitate the recognition of those patients
      most likely to respond favorably to PPI treatment.

PMID- 17037996
TI  - Autoimmune hemolytic anemia in patients with liver transplants for primary
      biliary cirrhosis: Three case reports and a review of the literature.
AB  - BACKGROUND: Hemolytic anemia is rare after liver transplant and is usually
      associated with ABO mistmatch, post-transplant lymphoproliferative disorders, or
      medications. CASE REPORTS: We report three patients who had undergone successful
      liver transplants for primary biliary cirrhosis (PBC) and developed direct
      antibody test positive autoimmune hemolytic anemia (AIHA) several years into
      uncomplicated post-transplant management. For two of the patients, the hemolysis
      responded to steroids and rituximab. One patient required a surgical splenectomy.
      DISCUSSION: AIHA is an immune-mediated hemolysis that has been reported in
      patients with PBC. There are no reports of AIHA in patients following liver
      transplantation for this disease. AIHA should be considered in stable PBC
      patients who develop anemia years after liver transplant.

PMID- 17037999
TI  - The art of reading sequence electropherograms.

PMID- 17038000
TI  - Interrelationship and familiality of dyslexia related quantitative measures.
AB  - Dyslexia is a complex gene-environment disorder with poorly understood etiology
      that affects about 5% of school-age children. Dyslexia occurs in all languages
      and is associated with a high level of social and psychological morbidity for the
      individual and their family; approximately 40-50% have persistent disability into
      adulthood. The core symptoms are word reading and spelling deficits, but several
      other cognitive components influence the core phenotype. A broad spectrum of
      dyslexia related phenotypes, including phonological decoding, phoneme awareness,
      orthographic processing, short-term memory, rapid naming and basic mathematical
      abilities, were investigated in large sample of 287 German dyslexia families. We
      explored the interrelationship between the component phenotypes using correlation
      and principal component analyses (PCA). In addition, we estimated familiality for
      phenotypes as well as for the factors suggested by PCA. The correlation between
      the component phenotypes varied between -0.1 and 0.7. The PCA resulted in three
      factors: a general dyslexia factor, a speed of processing factor and a
      mathematical abilities factor. The familiality estimates of single components and
      factors ranged between 0.25 and 0.63. Instead of analyzing single dyslexia
      related components, multivariate analyses including factor analytic approaches
      may help in the identification of susceptibility genes.

PMID- 17038001
TI  - Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin
      increases the incidence of graft rejection in children with aplastic anaemia who
      underwent allogeneic bone marrow transplantation from HLA-identical siblings.
AB  - The incidence of graft rejection was determined in 66 children with acquired
      aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related
      donor. Eleven of 65 evaluable patients experienced either early or late
      rejection. Multivariate analysis identified previous immunosuppressive therapy
      with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for
      graft rejection (relative risk: 16.6, P = 0.001). Patients who received ATG and
      CsA had a significantly lower probability of failure-free survival than those who
      did not (69.7 +/- 6.2% vs. 87.9 +/- 8.0%, P = 0.044). These results suggest that
      BMT should be instituted immediately in children with severe AA who have human
      leucocyte antigen-identical siblings.

PMID- 17038002
TI  - Benefit sharing: from obscurity to common knowledge.

PMID- 17038003
TI  - Women in developing countries and benefit sharing.
AB  - The aim of this paper is to show that any process of benefit sharing that does
      not guarantee the representation and participation of women in the decision
      making process, as well as in the distribution of benefits, contravenes a central
      demand of social justice. It is argued that women, particularly in developing
      countries, can be excluded from benefits derived from genetic research because of
      existing social structures that promote and maintain discrimination. The paper
      describes how the structural problem of gender-based inequity can impact on
      benefit sharing processes. At the same time, examples are given of poor women's
      ability to organise themselves and to achieve social benefits for entire
      communities. Relevant international guidelines (e.g. the Convention on
      Biodiversity) recognise the importance of women's contributions to the protection
      of biodiversity and thereby, implicitly, their right to a share of the benefits,
      but no mechanism is outlined on how to bring this about. The authors make a clear
      recommendation to ensure women's participation in benefit sharing negotiations by
      demanding seats at the negotiation table.

PMID- 17038004
TI  - North-South benefit sharing arrangements in bioprospecting and genetic research:
      a critical ethical and legal analysis.
AB  - Most pharmaceutical research carried out today is focused on the treatment and
      management of the lifestyle diseases of the developed world. Diseases that affect
      mainly poor people are neglected in research advancements in treatment because
      they cannot generate large financial returns on research and development costs.
      Benefit sharing arrangements for the use of indigenous resources and genetic
      research could only marginally address this gap in research and development in
      diseases that affect the poor. Benefit sharing as a strategy is conceptually
      problematic, even if one, as we do, agrees that impoverished indigenous
      communities should not be exploited and that they should be assisted in improving
      their living conditions. The accepted concept of intellectual property protection
      envisages clearly defined originators and owners of knowledge, whereas the
      concept of community membership is fluid and indigenous knowledge is, by its very
      nature, open, with the originator(s) lost in the mists of time. The delineation
      of 'community' presents serious conceptual and practical difficulties as few
      communities form discrete, easily discernable groups, and most have problematic
      leadership structures. Benefit sharing is no substitute for governments'
      responsibility to uplift impoverished communities. Benefit sharing arrangements
      may be fraught with difficulties but considerations of respect and equity demand
      that prior informed consent and consultation around commercialisation of
      knowledge take place with the source community and their government.

PMID- 17038005
TI  - Sharing the benefits of genetic resources: from biodiversity to human genetics.
AB  - Benefit sharing aims to achieve an equitable exchange between the granting of
      access to a genetic resource and the provision of compensation. The Convention on
      Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro,
      is the only international legal instrument setting out obligations for sharing
      the benefits derived from the use of biodiversity. The CBD excludes human genetic
      resources from its scope, however, this article considers whether it should be
      expanded to include those resources, so as to enable research subjects to claim a
      share of the benefits to be negotiated on a case-by-case basis. Our conclusion on
      this question is: 'No, the CBD should not be expanded to include human genetic
      resources.' There are essential differences between human and non-human genetic
      resources, and, in the context of research on humans, an essentially fair
      exchange model is already available between the health care industry and research
      subjects. Those who contribute to research should receive benefits in the form of
      accessible new health care products and services, suitable for local health needs
      and linked to economic prosperity (e.g. jobs). When this exchange model does not
      apply, as is often the case in developing countries, individually negotiated
      benefit sharing agreements between researchers and research subjects should not
      be used as 'window dressing'. Instead, national governments should focus their
      finances on the best economic investment they could make; the investment in
      population health and health research as outlined by the World Health
      Organization's Commission on Macroeconomics and Health; whilst international
      barriers to such spending need to be removed.

PMID- 17038006
TI  - Vicissitudes of benefit sharing of crop genetic resources: downstream and
      upstream.
AB  - In this article, we will first give a historic overview of the concept of benefit
      sharing and its appearance in official agreements, particularly with respect to
      crop genetic resources. It will become clear that, at present, benefit sharing is
      primarily considered as an instrument of compensation or exchange, and thus
      refers to commutative justice. However, we believe that such a narrow
      interpretation of benefit sharing disregards, and even undermines, much of its
      (historical) content and potency, especially where crop genetic resources are
      concerned. We argue that benefit sharing should not be based merely on
      commutative justice but rather on a broader model that is also grounded in the
      concept of distributive justice. This has repercussions for the application of
      benefit sharing, which we try to clarify by distinguishing between downstream and
      upstream benefit sharing. Upstream benefit sharing is not so much inspired by
      compensation for actions done, or the distribution downstream of benefits
      developed, but by the idea of shared decision-making on the research and
      development of resources fundamental to human welfare. Going upstream in the
      research process of crop genetic resources, and determining research agendas and
      improving crops according to the needs of the poor, benefit sharing may well be a
      tool to contribute to world food security and global justice. We concretize our
      ideas on upstream benefit sharing by introducing a set of criteria that determine
      the success of consultations on agricultural research agenda setting.

PMID- 17038007
TI  - Biodiversity, biopiracy and benefits: what allegations of biopiracy tell us about
      intellectual property.
AB  - This paper examines the concept of biopiracy, which initially emerged to
      challenge various aspects of the regime for intellectual property rights (IPR) in
      living organisms, as well as related aspects pertaining to the ownership and
      apportioning of benefits from 'genetic resources' derived from the world's
      biodiversity. This paper proposes that we take the allegation of biopiracy
      seriously due to the impact it has as an intervention which indexes a number of
      different, yet interrelated, problematizations of biodiversity, biotechnology and
      IPR. Using the neem tree case as an example, it describes activists' use of the
      term as one that involves a deliberate simplification of science and IPR.
      Additionally, it argues that in so doing, biopiracy is positioned as a touchstone
      that mobilizes actors and problems, and ultimately generates 'solutions' to the
      very challenges it creates. The paper will also encourage a view of biopiracy
      claims that does not always treat them simply as claims of theft, or as a
      misallocation of benefits, but rather as claims that are designed to raise
      broader questions about the IPR system itself. It concludes by advocating that,
      in order to properly understand how to address biopiracy, we must be prepared to
      move beyond the current narrow readings to develop a more complete picture of the
      term's influence in challenging how, and by whom, the decisions about what is
      natural and what is invented come to be made.

PMID- 17038009
TI  - 'Schools without walls?' Developments and challenges in dental outreach teaching 
      report of a recent symposium.
AB  - During the 2004 annual meeting of the International Association for Dental
      Research, the Education Research Group held a symposium on dental outreach
      teaching. After a brief introduction, which reviews relevant aspects of the
      relatively sparse literature, this paper summarises the proceedings, the themes
      and conclusions that emerged and the research issues that were identified. It
      aims to describe aspects of current practice around the world and to promote
      future discussion. Presenters gave details of outreach programmes for dental
      undergraduates in Australia, Finland, Malaysia (and Southeast Asia), the United
      Kingdom and the United States. From these presentations four themes emerged. They
      were: reasons for the introduction of outreach teaching, its perceived beneficial
      effects, organisational issues, educational issues. The reasons included a
      recognition of the need to educate dental undergraduates as members of 'care
      teams' in the environments and communities where they were ultimately like to
      work and the current shortage of both suitable patients and teachers (faculty) in
      many dental schools. A wide range of potential benefits and some disadvantages
      were identified. The organisational issues were, in the main, seen to relate to
      finance and administration. The educational issues included the need to train and
      monitor the performance of teachers at outreach clinics and to assess the
      performance of the undergraduates whilst at the outreach locations. It was
      concluded that new technology made it easier to teach at a distance and it was
      possible to create a dental 'school without walls'. It was recognised that few
      evaluations of dental outreach teaching have been carried out and that there were
      many research questions to be answered, including: whether it should be a
      voluntary or compulsory part of the undergraduate curriculum, how long it should
      last and what type of outcomes should be assessed.

PMID- 17038010
TI  - The oral ecosystem: implications for education.
AB  - We propose a model that is applicable to oral health education. The model
      describes the oral cavity in a complexity-based ecological context. This concept
      includes the premise that factors from different organisational levels
      (biological, individual, community, society) interact in a complex way with the
      potential to 'stress' the ecosystem and thereby provoke changes. This mode of
      action complies with the understanding of the oral cavity as a complex adaptive
      system. An ecological model is actively used in the undergraduate problem-based
      curriculum at the Faculty of Odontology, Malmo University, Sweden and has
      recently been applied as a conceptual basis for the new dental curriculum being
      established at the University of Tromso in Northern Norway. The purpose is to
      encourage and promote an ecological, health-oriented view and to stimulate
      reflections on premises for oral health and diseases in an integrated context.

PMID- 17038011
TI  - The use of articulators in UK dental schools.
AB  - The increasing complexity of many restorative procedures often involves
      articulation of study and working casts to ensure accurate fabrication of
      restorations. Correct selection and use of articulators can be crucial to
      successful restoration. The aim of this paper is to determine which articulators
      are recommended for various restorative procedures in UK dental schools, for use
      by undergraduate students. A questionnaire-based study of all UK dental schools
      was carried out, with a 100% response rate. Recommended articulator application
      for specified procedures was established from the literature and questionnaire
      results were compared with this. The results indicated that dental schools in the
      UK generally teach appropriate articulator use for most procedures. However,
      there are some limited areas of what may be argued to be inappropriate
      recommendation in some establishments.

PMID- 17038012
TI  - Difficulties encountered at the beginning of professional life: results of a 2003
      pilot survey among undergraduate students in Paris Rene Descartes University
      (France).
AB  - In addition to dental hospital clinical activity, dental students at Paris Rene
      Descartes University have the opportunity in their final year of study to
      practise clinically in a dental office, as associates. This paper outlines a
      pilot, experimental study designed to assess student reaction to this Vocational
      Clinical Activity (VCA) in order to identify relevant weaknesses of the
      undergraduate programme. Using questionnaires, data were collected for each of
      the following clinical or management skills: clinical difficulty, therapeutic
      decision-making, patient/practitioner relationship, time management,
      administrative matters and technical problems. Students were asked to rank each
      item in order of difficulty (1, high level to 6, low level). A high response rate
      was observed (90%) among the 50 undergraduate VCA students. The results pointed
      out three main difficulties encountered by undergraduate students during the VCA:
      time management (90% of the students), administrative matters (85% of the
      students) and clinical decision-making (80% of the students). These preliminary
      results need further investigation. However, they give us the incentive to carry
      on with this type of assessment and to extend it to young, qualified colleagues'
      perceptions and to other French Universities.

PMID- 17038013
TI  - A survey on the preference for continuing professional dental education amongst
      general dental practitioners who attended the 26th Asia Pacific Dental Congress.
AB  - AIMS: To identify the subjects of interest and to examine the modes as well as
      means of study for continuing professional dental education amongst general
      dental practitioners who attended the 26th Asia Pacific Dental Congress, 28 May-1
      June 2004, Hong Kong. METHODS: A total of 381 general dental practitioners as the
      registered conference delegates from Hong Kong, Mainland China and other Asia
      Pacific regions were randomly selected for the present survey. The survey was
      conducted through face-to-face interviews by a group of practising dentists in
      Hong Kong. RESULTS: Overall, orthodontics and prosthodontics were the most
      popular subjects for clinical degree programmes, whilst oral implantology and
      cosmetic dentistry were the highly preferred subjects for continuing education
      courses. Concerning the preferred mode of study for degree programmes, the part
      time study mode was chosen by 68.3% of the participating dentists. A didactic
      teaching approach was preferred by most of the participants (81.7%) for
      postgraduate study. The majority of the interviewees (76.5%) were interested in a
      proposed clinical degree programme to be offered jointly by The University of
      Hong Kong and a leading university in the Mainland. Overall, there was no marked
      difference in the preference for continuing dental education amongst the
      respondents from Hong Kong, Mainland China and other Asia-Pacific regions.
      CONCLUSIONS: The present survey shows the currently preferred specialty areas and
      subjects for continuing professional dental education amongst the general dental
      practitioners who attended the 26th Asia Pacific Dental Congress, with didactic
      teaching as the most preferred mode of study on a part-time basis.

PMID- 17038014
TI  - Tutor perceptions of the use of a reflective portfolio within a pastoral tutor
      system to facilitate undergraduate personal development planning.
AB  - All Higher Education Institutions in the UK are now required to provide
      transcripts of student activity and outcomes of summative assessments. In
      addition, the student should be able to reflect on their learning and plan their
      own development. This article reports on the staff evaluation of the use of a
      reflective portfolio facilitating the production of highly individualised
      personal development plans within an existing tutor system. A number of
      significant issues are highlighted; tutor systems adopting this approach must
      maintain flexibility for managing student crises when they arise, the difference
      between appraisal and assessment needs clear definition for both students and
      tutors, training in basic mentoring skills should be provided for all tutors,
      tutors should be aware of the difficulties many students experience with
      reflection and also be alert to the over reflective learner.

PMID- 17038015
TI  - Implementing an Objective Structured Clinical Examination (OSCE) in dental
      education: effects on students' learning strategies.
AB  - OBJECTIVES: To investigate the effect of an Objective Structured Clinical
      Examination (OSCE) on dental students' learning strategies and competence to
      manage periodontal diseases in patients. The implemented OSCE was expected to be
      superior to the existing Written Exam in fostering the acquisition of clinical
      competencies in terms of study strategies that are more oriented towards clinical
      practice, longer study time, greater clinical proficiency, and more realistic
      self-assessment. MATERIAL AND METHODS: After a clinical course in periodontology,
      72 third year dental students were assessed summatively, either using a Written
      Exam or an OSCE (P-OSCE). The students were informed beforehand about the
      assessment formats. The self-assessed clinical competence, study time and
      strategies (i.e. practice with a manikin, peers and patient case) were evaluated
      by means of a questionnaire. After a comprehensive dental care course, all 72
      students were assessed by an overall end-of-year OSCE, in which three periodontal
      stations were included 'measuring pockets', 'educating patients' and 'tracing an
      X-ray with bone-loss'. The competence of the previous Written Exam group and the
      P-OSCE group was investigated by determining the mean scores and pass-fail scores
      of three periodontal test-stations as well as the total score of the end-of-year
      OSCE. The degree of realistic self-assessment was studied by correlating the self
      assessed competencies as evaluated by means of the questionnaire with the total
      score of the end-of-year OSCE. RESULTS: Self-assessed clinical competence, study
      time and study strategies showed no differences between the P-OSCE and the
      Written Exam-group. The clinical competence determined in the test-station
      'measuring pockets' in the end of year overall OSCE was higher for the P-OSCE
      group (P = 0.05) when compared with the Written Exam group; the two groups
      performed equally well in the test station 'educating patients', whereas the
      performance in 'tracing an X-ray with bone-loss' was better in the Written Exam
      group. This group also had a higher total score in the end-of-year OSCE (P =
      0.05). The degree of realistic self-assessment was higher in the P-OSCE group
      than in the Written Exam group: in the P-OSCE group the self-assessed clinical
      competencies correlated significantly with the total score of the overall end-of
      year OSCE (P < or = 0.05). CONCLUSIONS: No effects of the implementation of an
      OSCE in undergraduate periodontal education were observed in study strategies,
      but the implementation of an OSCE in undergraduate periodontal education appears
      to stimulate learning, resulting in greater achievement of specific clinical
      competence and a greater level of realistic self-assessment.

PMID- 17038016
TI  - Reasons for choosing dentistry as a career: a study involving male and female
      first-year students in Peru.
AB  - The aim of this study was to compare the reported reasons to choose dentistry as
      a career between Peruvian male and female first-year students. A self-completion
      questionnaire was administered to 75 first-year students registered at the
      Faculty of Dentistry of the Universidad Peruana Cayetano Heredia, Lima, Peru. The
      questionnaire comprised 16 items grouped into four categories (economic,
      professional, vocational and personal background). Students rated the importance
      of each item for selecting dentistry as a career on a Likert-type scale of five
      points. The Mann-Whitney test was used to compare groups and item scores by
      gender. A male/female proportion of 1/2.1 was found in the pool of participating
      students. When group and item scores were compared between genders, statistically
      significant differences were only found for vocational and personal background
      reasons (P < 0.05); however, the three reasons that obtained higher scores for
      each gender were found to be different. It is recommended that further studies be
      conducted to increase the sample, by extending the study and evaluating not only
      reasons for choosing dentistry, but also other factors that may influence the
      decision.

PMID- 17038017
TI  - Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7-kb
      beta-globin gene deletion.
AB  - A young woman originally from Cape Verde islands presented with mild sickle cell
      disease. Her blood counts and hemoglobin analysis results initially suggested
      that she might be either homozygous for the sickle cell hemoglobin (Hb S) with
      concomitant alpha-thalassemia, or compound heterozygous for Hb S and beta0
      thalassemia, deletional deltabeta-thalassemia or hereditary persistence of fetal
      hemoglobin (HPFH). We utilized a novel polymerase chain reaction (PCR)-based
      screening technique and found a hitherto unrecognized 7.7-kb deletion, starting
      from the HBB IVSII to 3' downstream of the beta-globin gene. This diagnostic
      approach can be applied to decipher other similar deletional mutations. This is
      the second known deletion that removes the 3'-end but preserves the integrity of
      the 5'-end of the beta-globin gene. Furthermore, the identification of the
      deletion allows proper genetic counseling for affected families.

PMID- 17038018
TI  - Correlation of echocardiography parameters with cardiac magnetic resonance
      imaging in transfusion-dependent thalassaemia major.
AB  - BACKGROUND AND OBJECTIVE: Heart iron load (cardiac Fe) can be indirectly
      quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited,
      whereas echocardiography (Echo) is relatively inexpensive and readily available.
      The objective was to find Echo parameters that may be useful for predicting
      cardiac Fe. DESIGN AND METHODS: We compared a number of parameters derived from
      Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR
      study. RESULTS: All patients with decreased left ventricular (LV) function had
      cardiac Fe. After removing those patients from the analysis, the total diameter
      index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the
      diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9%
      respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting
      iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2
      or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate
      cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%,
      respectively, but with low sensitivity. INTERPRETATION AND CONCLUSIONS: Echo
      parameters for cardiac Fe prediction have restricted value, whereas CMR is
      essential to assess cardiac Fe. However, patients with decreased LV systolic
      function should be considered a priori as having cardiac Fe, and chelation
      therapy should be intensified. This also applies to patients who have the above
      described Echo criterion values, even if CMR is not available. Once a patient is
      found by CMR to have cardiac Fe, then the above Echo criterion values may be
      useful for ongoing monitoring.

PMID- 17038019
TI  - Serum calcium is an independent predictor of quality of life in multiple myeloma.
AB  - Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a
      frequent complication of this disease. We examined the association between serum
      calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the
      time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30
      questionnaire were analysed by means of linear regression analysis and a curve
      fitting program. Serum calcium was independently related to appetite loss,
      nausea/vomiting and physical functioning (P < 0.001) and to cognitive functioning
      (P = 0.001), i.e. scores reflecting symptoms that are well known in non-malignant
      hypercalcaemia. In addition, we found a highly significant independent
      relationship between serum calcium and the scores for fatigue and pain (P <
      0.001). Serum calcium appeared to be as strong a predictor for fatigue as the
      concentration of haemoglobin. A cubic model (y = a + bx3) fitted the data
      slightly better than the simple linear model (y = a + bx) and suggested worsening
      QOL scores at levels of serum calcium above 2.5-3.0 mmol/L. Hypercalcaemia in
      patients with multiple myeloma seems to be associated with the same symptoms as
      in non-malignant hypercalcaemia. In addition, an increased level of serum calcium
      may aggravate the pain and fatigue caused by the skeletal disease itself.

PMID- 17038020
TI  - The importance of EEG and variability of MRI findings in acute hemorrhagic
      leukoencephalitis.

PMID- 17038021
TI  - Patient with adult-onset congenital neuromuscular disease with uniform type 1
      fibers.

PMID- 17038027
TI  - Epstein-Barr virus-associated primary leptomeningeal lymphoma.

PMID- 17038028
TI  - Cost of disorders of the brain in Europe.

PMID- 17038029
TI  - Rhabdomyolysis associated with hyponatremia and adrenal insufficiency.

PMID- 17038030
TI  - EFNS guidelines on pharmacological treatment of neuropathic pain.
AB  - Neuropathic pain treatment remains unsatisfactory despite a substantial increase
      in the number of trials. This EFNS Task Force aimed at evaluating the existing
      evidence about the pharmacological treatment of neuropathic pain. Studies were
      identified using first the Cochrane Database then Medline. Trials were classified
      according to the aetiological condition. All class I and II controlled trials
      (according to EFNS classification of evidence) were assessed, but lower-class
      studies were considered in conditions that had no top level studies. Only
      treatments feasible in an outpatient setting were evaluated. Effects on pain
      symptoms/signs, quality of life and comorbidities were particularly searched for.
      Most of the randomized controlled trials included patients with postherpetic
      neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes.
      These trials provide level A evidence for the efficacy of tricyclic
      antidepressants, gabapentin, pregabalin and opioids, with a large number of class
      I trials, followed by topical lidocaine (in PHN) and the newer antidepressants
      venlafaxine and duloxetine (in PPN). A small number of controlled trials were
      performed in central pain, trigeminal neuralgia, other peripheral neuropathic
      pain states and multiple-aetiology neuropathic pains. The main peripheral pain
      conditions respond similarly well to tricyclic antidepressants, gabapentin, and
      pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more
      refractory. There are too few studies on central pain, combination therapy, and
      head-to-head comparison. For future trials, we recommend to assess quality of
      life and pain symptoms or signs with standardized tools.

PMID- 17038031
TI  - Review of the therapeutic management of Parkinson's disease. Report of a joint
      task force of the European Federation of Neurological Societies and the Movement
      Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's
      disease.
AB  - The aim of the study was to provide evidence-based recommendations for the
      management of early (uncomplicated) Parkinson's disease (PD), based on a review
      of the literature. Uncomplicated PD refers to patients suffering from the
      classical motor syndrome of PD only, without treatment-induced motor
      complications and without neuropsychiatric or autonomic problems. MEDLINE,
      Cochrane Library and International Network of Agencies for Health Technology
      Assessment (INAHTA) database literature searches were conducted. National
      guidelines were requested from all European Federation of Neurological Societies
      (EFNS) societies. Non-European guidelines were searched for using MEDLINE. Part I
      of the guidelines deals with prevention of disease progression, symptomatic
      treatment of motor features (parkinsonism), and prevention of motor and
      neuropsychiatric complications of therapy. For each topic, a list of therapeutic
      interventions is provided, including classification of evidence. Following this,
      recommendations for management are given, alongside ratings of efficacy.
      Classifications of evidence and ratings of efficacy are made according to EFNS
      guidance. In cases where there is insufficient scientific evidence, a consensus
      statement (good practice point) is made.

PMID- 17038032
TI  - Review of the therapeutic management of Parkinson's disease. Report of a joint
      task force of the European Federation of Neurological Societies (EFNS) and the
      Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated)
      Parkinson's disease.
AB  - To provide evidence-based recommendations for the management of late
      (complicated) Parkinson's disease (PD), based on a review of the literature.
      Complicated PD refers to patients suffering from the classical motor syndrome of
      PD along with other motor or non-motor complications, either disease-related
      (e.g. freezing) or treatment-related (e.g. dyskinesias or hallucinations).
      MEDLINE, Cochrane Library and INAHTA database literature searches were conducted.
      National guidelines were requested from all EFNS societies. Non-European
      guidelines were searched for using MEDLINE. Part II of the guidelines deals with
      treatment of motor and neuropsychiatric complications and autonomic disturbances.
      For each topic, a list of therapeutic interventions is provided, including
      classification of evidence. Following this, recommendations for management are
      given, alongside ratings of efficacy. Classifications of evidence and ratings of
      efficacy are made according to EFNS guidance. In cases where there is
      insufficient scientific evidence, a consensus statement ('good practice point')
      is made.

PMID- 17038033
TI  - Critical illness polyneuropathy and myopathy: clinical features, risk factors and
      prognosis.
AB  - Acquired neuromuscular weakness due to critical illness polyneuropathy and
      myopathy (CIPNM) frequently develops in patients hospitalized in the intensive
      care unit for more than 1 week. CIPNM may present with muscle weakness and
      failure to wean from mechanical ventilation, but is discovered more often and
      earlier by electrophysiological examination. In this review, the incidence,
      clinical and electrophysiological features, differential diagnosis and prognosis
      of CIPNM will be described. Risk factors for CIPNM are sepsis or systemic
      inflammatory response syndrome and the severity of multi-organ failure. Presence
      of CIPNM is associated with higher mortality rate, prolonged duration of
      mechanical ventilation and prolonged rehabilitation. The majority of survivors
      with CIPNM have persistent functional disabilities and a reduced quality of life.
      There is need for new therapeutic strategies to prevent or minimize CIPNM in
      critically ill patients.

PMID- 17038034
TI  - Chronic polyneuropathy and Lyme disease.
AB  - Infection of the peripheral nervous system with Borrelia burgdorferi can present
      as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF)
      pleocytosis and intrathecal antibody production against B. burgdorferi, or as an
      asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA)
      and normal CSF findings. According to North American studies, it can also present
      as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations.
      Our purpose was to investigate the prevalence of B. burgdorferi antibodies in
      patients presenting with isolated chronic polyneuropathy (PN) in a European
      region with high incidence of Lyme disease. Sera from 209 PN patients and 247
      healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia
      burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%)
      healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was
      similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified
      etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal
      spinal fluid white cell count and they did not differ clinically or
      electrophysiologically from PN patients without antibodies. None of 20 antibody
      positive PN patients responded to antimicrobial treatment. The study shows that,
      in Europe, chronic distal PN without ACA or other Lyme manifestations is very
      rarely caused by a B. burgdorferi infection.

PMID- 17038035
TI  - Apolipoprotein E epsilon4 allele is associated with the volume of white matter
      changes in patients with lacunar infarcts.
AB  - The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and
      white matter changes (WMC) in elderly subjects or patients with Alzheimer's
      disease is controversial. To investigate this polymorphism in relation to WMC in
      patients with lacunar infarcts, we prospectively observed 67 patients with acute
      lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined
      using a nested polymerase chain reaction. WMC were measured quantitatively and
      were divided into two groups, severe and mild, with the mean volume of WMC as the
      cut point. Twenty-two patients (33%) had severe WMC. There was a significant
      difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles
      between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles
      was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P
      = 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients
      with lacunar infarcts. Further studies are required to confirm this finding.

PMID- 17038036
TI  - Isolated ocular motor nerve palsy in dural carotid-cavernous sinus fistula.
AB  - The incidence of dural carotid-cavernous sinus fistula (DCCF) presenting as
      isolated ocular motor nerve palsies without congestive ocular features is
      unknown. We reviewed the DCCF patients in our hospital during the last 10 years
      to elucidate the clinical and neuroradiological features of DCCF with isolated
      ocular motor nerve palsy. Eleven amongst the 33 DCCF patients presented isolated
      ocular motor nerve palsy. All the 11 patients underwent brain CT/CT angiography
      (CTA) and/or MRI/MR angiography (MRA), before the digital subtraction angiography
      (DSA). The compromised nerves were the oculomotor nerve in eight (72.7%),
      abducens nerve in two (18.2%) and trochlear nerve in one (9.1%). Brain CT and/or
      CTA were conducted in four patients but all unremarkable. MRI and/or MRA were
      performed in nine patients and six of them showed compatible findings of DCCF.
      The diagnoses of DCCFs were confirmed by DSA and all were posterior-draining
      type. The outcome was good, with a total recovery rate of 54.5% within 12 months.
      Thirty-three percent (11 of 33) of our DCCF patients presented with isolated
      ocular motor nerve palsy, which is not uncommon. MRI and MRA are of value in the
      initial evaluation, but DSA is necessary for the accurate diagnosis and treatment
      planning.

PMID- 17038037
TI  - Examination of the diagnostic validity of 'headache attributed to whiplash
      injury': a controlled, prospective study.
AB  - Acute and chronic headache attributed to whiplash injury are new diagnostic
      entities in the International Classification of Headache Disorders, second
      edition. A main objective of the present study was to assess the validity of
      these nosologic entities by studying the headache pattern in an inception cohort
      of 210 rear-end car collision victims and in 210 matched controls. Consecutive
      drivers involved in rear-end collisions were identified from the daily records of
      the Traffic Police Department of Kaunas, Lithuania. A standard self-report
      questionnaire was sent to the drivers between 2 and 7 days after the collision,
      and their passengers were recruited as well. Headache and neck pain were
      evaluated within 7 days of the collision, at 2 months and 1 year after the
      collision. A control group of non-traumatized subjects received questionnaires at
      the time of the selection and 1 year later. Of the 75 collision victims who
      developed headache within the first 7 days of the collision, 37 had a clinical
      picture in accordance with the criteria for acute whiplash headache (i.e.,
      concomitant neck pain) and 38 did not. For acute headache after collision,
      concomitant neck pain was of no relevance to the headache type or its course. In
      both these subgroups, migraine and tension-type headache could be diagnosed in
      similar proportions and the prognosis after 2 months and 1 year was also similar.
      Preexisting headache was a strong prognostic factor in both groups for both acute
      and chronic pain. Compared with the non-traumatized control group, the 1-year
      incidence of new or worsened headache, or of headache improvement, was the same.
      A likely interpretation of the data is that acute headaches after rear-end car
      collisions mainly represent episodes of a primary headache precipitated by the
      stress of the situation. We conclude that the nosologic validity of both acute
      and chronic whiplash headache is poor as the headaches, in accordance with the
      criteria lack distinguishing clinical features and have the same prognosis
      compared with headaches in a control group.

PMID- 17038038
TI  - Headache prevalence related to smoking and alcohol use. The Head-HUNT Study.
AB  - The aim of this study was to examine a possible association between smoking,
      alcohol and headache in a large population-based cross-sectional study. A total
      of 51,383 subjects completed a headache questionnaire and constituted the 'Head
      HUNT' Study. Questionnaire-based information on smoking was available in 95% and
      on alcohol in 89% of the individuals. Associations were assessed in multivariate
      analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals
      (CI). Prevalence rates for headache were higher amongst smokers compared with
      never smokers, most evident for those under 40 years smoking more than 10
      cigarettes per day (OR 1.5, 95% CI 1.3-1.6). Passive smoking was also associated
      with higher headache prevalence. For alcohol use, there was a tendency of
      decreasing prevalence of migraine with increasing amounts of alcohol consumption
      compared with alcohol abstinence. Only with regard to symptoms indicating alcohol
      overuse, a positive association with frequent headache was found. The association
      between headache and smoking found in the present study raises questions about a
      causal relationship, e.g. that smoking causes headache or that it allays stress
      induced by headache. The observed negative association between migraine and
      alcohol consumption is probably explained by the headache precipitating
      properties of alcohol.

PMID- 17038039
TI  - Validation of the deCODE Migraine Questionnaire (DMQ3) for use in genetic
      studies.
AB  - We assessed the reliability of the diagnosis of migraine with aura (MA) and
      migraine without aura (MO) based on the third edition of the deCODE Migraine
      Questionnaire (DMQ3) using a physician-conducted interview as an empirical index
      of validity. Amongst Danish migraine families recruited from specialist practice
      we selected 200 cases diagnosed according to the International Classification of
      Headache Disorders 2nd Edition in a validated physician-conducted telephone
      interview: 50 patients with exclusively MA, 50 with both MA and MO, 50 with
      exclusively MO and 50 controls. A written copy of the DMQ3 was mailed to the
      participant. The DMQ3-based diagnosis was compared with the interview-based
      diagnosis. Overall, the DMQ3 diagnosed migraine (MA, MO or both) with a
      sensitivity of 99% (109/110), a specificity of 86% (32/37) and a kappa statistic
      of 0.89. The most reliable subtype of migraine was MA (with or without co
      occurring attacks of MO) which was diagnosed with a sensitivity of 92% (71/77), a
      specificity of 93% (65/70) and a kappa statistic of 0.85. Exclusively MO was
      diagnosed with a sensitivity of 91% (30/33), a specificity of 93% (106/114) and a
      kappa statistic of 0.80. Weakest was the diagnosis of both MO and MA which was
      diagnosed with a sensitivity of 63% (24/38), a specificity of 92% (100/109) and a
      kappa statistic of 0.57. In conclusion, the DMQ3 is a valid tool for diagnosing
      patients with migraine for genetic studies.

PMID- 17038040
TI  - Acute autonomic dysfunction contralateral to acute strokes: a prospective study
      of 100 consecutive cases.
AB  - Complex painful reflex syndrome is sometimes described in the chronic phase of
      stroke. Acute autonomic dysfunction (AAD), which is occasionally present in cases
      of acute stroke, has not been studied prospectively. The aim of the study was to
      investigate AAD on the hemibody contralateral to the lesion in the acute phase of
      stroke. One hundred consecutive patients (median age +/- interquartile range, 74
      +/- 21; range 19-93; 51 women: 80 +/- 17 and 49 men: 70 +/- 17 years) in the
      acute phase of stroke were studied prospectively. Changes in skin temperature or
      coloration, diaphoresis, pain, or edema were noted in the first 3 days post
      stroke. Associations between AAD and topography (cortical pre- and/or post
      central, insular, corona radiata, basal ganglia, internal capsule, thalamus, and
      brainstem), age, gender, ischemic or hemorrhagic etiology, or the presence of
      sensorimotor deficits or ataxia were examined using the chi-squared or Fisher's
      exact test and logistic regression analysis. AAD was found in 71% of the patients
      and showed a significant positive association with the presence of a lesion in
      the post-central cortex (P = 0.037), internal capsule (P = 0.005), basal ganglia
      (P = 0.002), or insula (P = 0.011) and a negative association with the presence
      of a lesion in the brainstem (P = 0.004). Multivariate logistic regression
      analysis including all studied topographic variables showed that only brainstem
      lesions were significantly associated with a decreased risk of developing AAD
      (odds ratio = 0.08, 95% confidence interval: 0.01-0.69, P = 0.022). AAD was not
      associated with age, gender, the ischemic or hemorrhagic nature of the lesion,
      the side of lesion, hypertonic or hypotonic paresis, or hyperreflexia or
      hyporeflexia. AAD was found in association with sensory deficits (P = 0.001) and
      contralateral hyperkinesia (P = 0.004). Acute AAD is significantly more likely to
      occur in the presence of hemispheric lesions involving sensory pathways from the
      cortex to the internal capsule and insula and is significantly less prevalent in
      the presence of brainstem lesions.

PMID- 17038041
TI  - Factors influencing hemorrhagic transformation in ischemic stroke: a
      clinicopathological comparison.
AB  - As hemorrhagic transformation (HTr) is a frequent complication and can worsen the
      outcome of acute ischemic stroke, our aim was to assess the risk factors of HTr.
      Using the database of our neuropathological laboratory, 245 consecutive acute
      ischemic stroke patients were analyzed. An exploratory logistic regression
      procedure was carried out to find the best multiple model identifying the factors
      associated with HTr. The autopsy revealed ischemic infarct in 175 (71%) and
      ischemic infarct with HTr in 70 (29%) patients. Mean age was 71.5 +/- 11.4 years
      (mean +/- SD) and 74.8 +/- 10.2 years (mean +/- SD), respectively. The multiple
      model confirmed age in case of embolic stroke, and diabetes mellitus and infarct
      size as independent risk factors of HTr. It seems that not serum glucose level
      but diabetes mellitus in the case history is an independent predictor of HTr.

PMID- 17038042
TI  - Stroke complicating pregnancy and the puerperium.
AB  - Stroke complicating pregnancy and the puerperium in Taiwan and the comparison
      between Western and Eastern countries have not been well studied. We identified
      retrospectively 32 cases of stroke from 66,781 deliveries, including 21
      intracranial hemorrhages and 11 cerebral infarctions from 1992 to 2004. The most
      common causes of intracranial hemorrhage were vascular anomaly (29%), pre
      eclampsia/eclampsia (24%), undetermined (24%) and coagulopathy (19%). The most
      common causes of cerebral infarction were cardioembolism (36%), cerebral venous
      thrombosis (27%) and pre-eclampsia/eclampsia (18%). Perinatal adverse outcome
      included two stillbirths, nine premature deliveries and four abortions. The
      compiled results of previous studies and ours revealed that intracranial
      hemorrhage appeared to be slightly more common in Taiwan (43-69%) than in the
      Western countries (33-52%). The average maternal mortality rate was 17.8% (range
      9-38) with 77.8% due to intracranial hemorrhage. The average incidence of stroke
      associated with pregnancy and the puerperium was 21.3 per 100,000 deliveries
      (range 8.9-67.1). Our study, different from the Western countries, showed that
      intracranial hemorrhage is slightly more common than cerebral infarction. Pre
      eclampsia/eclampsia is an important cause of stroke, however, the possibility of
      cardioembolism in cerebral infarction and vascular anomaly in intracranial
      hemorrhage should be studied.

PMID- 17038043
TI  - Asymptomatic pontine myelinolysis.
AB  - A 43-year-old lady presented with bilateral foot drop due to alcohol-related
      peripheral neuropathy. There was no history of electrolyte disturbance or altered
      consciousness. Cranial nerve, bulbar and pyramidal symptoms and signs were
      absent. Nerve conduction studies confirmed the neuropathy. Inadvertently
      requested neuroimaging of brain demonstrated signal change typical of central
      pontine myelinolysis. Asymptomatic pontine myelinolysis occurs rarely in
      alcoholics in the absence of bulbar dysfunction. It is important for physicians
      to be aware of the clinical entity of asymptomatic pontine myelinolysis to avoid
      misinterpretation of abnormalities detected on cerebral imaging in alcoholic
      individuals.

PMID- 17038044
TI  - Isolated sixth nerve palsy secondary to spontaneous intracranial hypotension.
AB  - We report the case of a 43-year-old gentleman who presented with an isolated left
      sixth nerve palsy in association with postural headache. Magnetic resonance
      imaging showed dural enhancement with downward displacement of the brainstem.
      This, in association with the signs, symptoms and findings on lumbar puncture,
      confirmed the diagnosis of spontaneous intracranial hypotension. Treatment was
      successful with epidural blood patching. The case is discussed and the relevant
      literature reviewed.

PMID- 17038045
TI  - Knowledge about the genetics of essential tremor in patients and their relatives.
AB  - In a face-to-face questionnaire-based survey involving a total of 111 essential
      tremor (ET) patients and their relatives, we demonstrated a general lack of
      genetic insight amongst our study subjects. There was no significant correlation
      between genetic knowledge of ET and age, level of education, disease duration or
      severity. A proactive effort is needed to encourage physicians managing ET
      patients to incorporate genetic information and education into their practice.

PMID- 17038047
TI  - Novel overlapping coding sequences in Chlamydia trachomatis.
AB  - Chlamydia trachomatis is the aetiological agent of trachoma and sexually
      transmitted infections. The C. trachomatis genome sequence revealed an organism
      adapted to the intracellular habitat with a high coding ratio and a small genome
      consisting of 1.042-kilobase (kb) with 895 annotated protein coding genes. Here,
      we repredict the protein-coding genes of the C. trachomatis genome using the gene
      finder EasyGene that was trained specifically for C. trachomatis, and compare it
      with the primary C. trachomatis annotation. Our work predicts 15 genes not listed
      in the primary annotation and 853 that are in agreement with the primary
      annotation. Forty two genes from the primary annotation are not predicted by
      EasyGene. The majority of these genes are listed as hypothetical in the primary
      annotation. The 15 novel predicted genes all overlap with genes on the
      complementary strand. We find homologues of several of the novel genes in C.
      trachomatis Serovar A and Chlamydia muridarum. Several of the genes have typical
      gene-like and protein-like features. Furthermore, we confirm transcriptional
      activity from 10 of the putative genes. The combined evidence suggests that at
      least seven of the 15 are protein coding genes. The data suggest the presence of
      overlapping active genes in C. trachomatis.

PMID- 17038048
TI  - Binding of Streptococcus gordonii to extracellular matrix proteins.
AB  - Knock-out mutants of Streptococcus gordonii Challis were constructed and assayed
      for binding to extracellular matrix proteins (EMPs) by enzyme-linked
      immunosorbent assay (ELISA). It was shown that (i) the mutant lacking the cell
      wall polysaccharide receptor could no longer bind type I and type II collagen,
      (ii) the mutant lacking the fibronectin-binding proteins CshA and FbpA was also
      strongly impaired in collagen binding and (iii) the mutant lacking the methionine
      sulfoxide reductase MsrA was significantly impaired in fibronectin binding. Our
      results indicate that binding to EMPs by S. gordonii is a multifactorial process
      controlled by genes located at three different chromosomal sites.

PMID- 17038049
TI  - Application of signature-tagged mutagenesis to the study of virulence of Erwinia
      amylovora.
AB  - To identify genes that contribute to the virulence of Erwinia amylovora in
      plants, 1892 mutants were created and screened in pools of < or =96 mutants using
      signature-tagged mutagenesis. Nineteen mutants were not recovered from apple
      shoots following inoculation, which suggested that the insertions in these
      mutants affected genes important for bacterial survival in planta. DNA flanking
      the Tn5 insertions in the 19 mutants was sequenced and analysed by blast. One
      mutant had a Tn5 insertion in amsE, a gene involved in the biosynthesis of
      exopolysaccaride (EPS). Fourteen mutants had insertions in loci that were
      implicated in biosynthesis or transport of particular amino acids or nucleotides,
      a site-specific recombinase active during cell division and several putative
      proteins of unknown function; the flanking DNA of the remaining four mutants
      lacked significant homology with any DNA in the database. When inoculated
      individually to hosts, 10 of the 19 mutants caused significantly less disease and
      multiplied less, as compared with the wild-type strain.

PMID- 17038050
TI  - Role of 1-hydroxybenzotriazole in oxidation by laccase from Trametes versicolor.
      Kinetic analysis of the laccase-1-hydroxybenzotriazole couple.
AB  - In the current studies, we used Lineweaver-Burke analysis to examine the role of
      1-hydroxybenzotriazole (HBT) in the oxidation of various compounds by laccase
      from Trametes versicolor. At low concentrations, HBT was a competitive inhibitor
      of the oxidation, but at high concentrations, it was a noncompetitive inhibitor.
      Analysis of the oxidation of ferrocytochrome c by the laccase-HBT couple showed
      that increasing the concentration of ferrocytochrome c did not affect the V(max)
      but reduced the apparent K(m). In addition, in the manganese peroxidase-Mn(II)
      reaction, which is a typical oxidation system by mediator, the apparent K(m) and
      V(max) increased as the concentration of the substrate 2,6-dimethoxyphenol was
      increased. These results indicate that HBT is involved in the binding of laccase
      and substrates that laccase cannot oxidize alone.

PMID- 17038051
TI  - Silencing of natural interferon producing cell activation by porcine circovirus
      type 2 DNA.
AB  - Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells
      (NIPCs) impairs the induction of interferon (IFN)-alpha and tumour necrosis
      factor (TNF)-alpha by cytosine-phosphorothioate-guanine (CpG)
      oligodeoxynucleotides (ODNs), thereby preventing both their autocrine maturation
      and the paracrine maturation of myeloid dendritic cells (DCs). The present study
      shows that the PCV2-mediated inhibition of NIPCs was mediated by viral DNA,
      although it was independent of virus replication. The inhibitory effect of PCV2
      DNA was more diversified than if it had simply targeted CpG-ODN-induced cytokines
      (IFN-alpha, TNF-alpha, interleukin-6, IL-12). A broad spectrum inhibition was
      noted, affecting responses induced by toll-like receptor (TLR)-7 and TLR9
      agonists, as well as viruses including pseudorabies virus, transmissible
      gastroenteritis virus and classical swine fever virus. From these results, it
      would appear that PCV2 DNA can induce a dominant negative signal influencing
      independent pattern recognition receptor-induced activation cascades. Despite a
      concomitant internalization of PCV2 DNA and CpG-ODNs, no colocalization was
      observed, indicating that PCV2 DNA and CPG-ODNs may not target the same receptor.
      This study describes a novel modulation of the innate immune response, which
      would render the host more susceptible to secondary or concomitant microbial
      infections.

PMID- 17038053
TI  - Oral hygiene practices, periodontal conditions, dentition status and self
      reported bad mouth breath among young mothers, Tanzania.
AB  - OBJECTIVES: To determine the oral hygiene practices, periodontal conditions,
      dentition status and self-reported bad mouth breath (S-BMB) among young mothers.
      STUDY PARTICIPANTS AND METHODS: This was a cross-sectional descriptive study
      conducted at Muhimbili National Hospital, Dar es Salaam, Tanzania. A total of 302
      postpartum mothers, aged 14-44 years, were interviewed on oral hygiene practices
      and S-BMB using structured questionnaire. Oral hygiene, dentition and periodontal
      status were assessed using the Community Periodontal Index probe and gingival
      recessions (GR) using Williams Periodontal probe. RESULTS: Tooth brushing
      practice was 99%; tongue brushing (95%), plastic toothbrush users (96%), chewing
      stick (1%), wooden toothpicks (76%), dental floss (<1%); and toothpaste (93%).
      The prevalence of plaque and gingival bleeding on probing was 100%, gum bleeding
      during tooth brushing (33%), calculus (99%), probing periodontal pocket depth
      (PPD) 4-5 mm (27%), PPD 6+ mm (3%), GR 1+ mm (27%) and tooth decay (55%). The
      prevalence of S-BMB was 14%; the S-BMB had higher mean number of sites with
      plaque compared to the no S-BMB group (P=0.04). Factors associated with S-BMB
      were gum bleeding on tooth brushing (OR=2.4) and PPD 6+ mm (OR=5.4). CONCLUSION:
      Self-reported bad mouth breath is a cause of concern among young mothers, and
      associated significant factors were gum bleeding on tooth brushing and deep
      periodontal pockets of 6+ mm. Further research involving clinical diagnosis of
      bad mouth breath and intervention through oral health promotion and periodontal
      therapy are recommended. CLINICAL RELEVANCE: This study provides baseline
      information on oral health status and the complaint on bad mouth breath which
      necessitates in the future need for objective assessment, diagnosis and
      management of bad mouth breath for enhanced social and professional interaction
      without embarrassment.

PMID- 17038054
TI  - Oral health knowledge and practices among Dar es Salaam institutionalized former
      street children aged 7-16 years.
AB  - OBJECTIVES: To find out level of knowledge on causes and prevention of dental
      caries and bleeding gums, oral hygiene and eating practices among
      institutionalized former street children. METHODS: A structured standardized
      questionnaire was used to collect data for this study. Chi-square test was used
      to test for significant differences. RESULTS AND CONCLUSIONS: Eighty-eight per
      cent and 83% of the children knew the cause of tooth decay and bleeding gums
      respectively and 17-68% were aware of preventive measures. At the institutions
      visited, 92% of the children said they brush their teeth but 74% brushed when
      living on the streets, this difference was significant (chi2=4.40, P=0.05). About
      half did not use toothpaste during street life, whilst 8% do not use toothpaste
      at institutions, the difference was significant (chi2=5.081, P=0.025). Almost 22%
      use sweets and biscuits at institutions, about 44% used the snacks when living on
      the streets, the differences were significant (chi2=3.798, P=0.04, and
      chi2=3.893, P=0.04). Only 6% use sodas and sweetened juices at institutions,
      while 32-36% used the drinks during street life, the differences were significant
      (chi2=4.38 P=0.05 and chi(2)-12.87, P=0.01). The findings of this study show that
      most former street children are aware of the causes of dental caries and bleeding
      gums but have poor knowledge on prevention of the two diseases. Furthermore,
      children living on the streets are more likely to eat cariogenic foods and have
      poor oral hygiene practices.

PMID- 17038055
TI  - Screening for type 2 diabetes mellitus using gingival crevicular blood.
AB  - This study was conducted to assess the usefulness of the gingival crevicular
      blood for estimating the glucose level during routine periodontal examination
      using Xitux Diagnostics Smart-X self-monitoring blood glucose device among
      Jordanian patients attending dental teaching clinics. A total of 34 type 2
      diabetic patients (18 males and 16 females) and 26 non-diabetic patients (14
      males and 12 females) participated in this study. Glucose level was measured in a
      sample of gingival crevicular blood and in another sample obtained by finger
      puncture using a self-monitoring device. Glucose measurements from gingival
      crevicular blood samples, ranged from 57 to 250 mg dl-1 with a mean of 125.4+/
      60.7 mg dl-1 (+/-SD) and glucose measurements obtained by finger puncture, ranged
      from 62 to 263 mg dl-1 with a mean of 131.9+/-61.1 mg dl-1. Pearson's correlation
      coefficient was performed to assess the correlation between the glucose
      measurements in these two samples. Pearson's correlation coefficient showed an
      almost perfect positive correlation between the gingival readings and finger
      puncture readings (r=0.997, P<0.0001). In conclusion, gingival crevicular blood
      can provide an acceptable source for measuring blood glucose level. However, the
      technique to obtain an acceptable blood sample from gingival crevices is not
      always feasible which would limit its application as a clinical practice.
      Additional studies that refine this technique and use larger sample size are
      recommended.

PMID- 17038057
TI  - Siwak as a oral hygiene aid in patients with fixed orthodontic appliances.
AB  - OBJECTIVES: The aims of this study were to compare the mechanical efficacy of
      Siwak in plaque control and gingival health conditions in subjects wearing fixed
      orthodontic appliances compared with standard and orthodontic toothbrushes.
      METHODS: Forty male patients with a mean age of 17.20+/-4.01 years, wearing fixed
      orthodontic appliances were included in this study. Following a session of
      scaling and polishing, which established a situation with minimal gingival
      inflammation and close to zero amounts of dental plaque, all patients were
      instructed to use a standard soft toothbrush for 1 week after which they were
      randomly and equally allocated to one of four groups: (i) a manual toothbrush
      group; (ii) an orthodontic toothbrush group; (iii) a Siwak group; and (iv) a
      combination of Siwak and an orthodontic toothbrush group. All patients were
      instructed to brush their teeth three times a day. All patients were scored for
      plaque and gingivitis 1 week after scaling and polishing and 2 weeks following
      group assignment. RESULTS: A similar effect of Siwak to that of soft and
      orthodontic toothbrushes with respect to plaque control in patients with fixed
      orthodontic appliances was found. It was the combined use of Siwak and
      orthodontic toothbrush that provided the best plaque control in such patients.
      Gingival condition was better in the Siwak groups whether used solely or in
      combination with an orthodontic toothbrush. CONCLUSION: The use of Siwak promotes
      gingival health in patients with orthodontic appliances.

PMID- 17038056
TI  - A comparison of two chlorhexidine gel brushing regimens and a conventional
      toothpaste brushing regimen for the development of tooth staining over a 6-week
      period.
AB  - AIMS: A single-centre, randomized single-blind parallel study was undertaken to
      compare staining seen with three brushing regimens and to determine subject
      perception of side effects such as staining and effects on taste. METHODS: This 6
      week parallel study used 157 volunteers who were randomized into one of three
      treatment groups: (i) brushing in the morning and evening with a normal dose of a
      1% chlorhexidine gel, (ii) brushing with a low dose of chlorhexidine gel in the
      evening and a whitening dentifrice in the morning, and (iii) brushing with a
      standard fluoride paste in the morning and evening. Following home usage of their
      allocated products, the study volunteers returned after 3 and 6 weeks to record
      the amount of stain present. After the 6-week period, subject perception of taste
      and stain acceptability was determined using a questionnaire. RESULTS: After 6
      weeks of use of the low-dose chlorhexidine gel and whitening dentifrice,
      significantly more stain was seen compared with the use of a standard dentifrice
      (P<0.0001). Similarly, significantly more stain was seen with use of the normal
      dose chlorhexidine gel compared with the low-dose gel and whitening dentifrice
      (P=0.0007). Approximately 30% of individuals on the low-dose chlorhexidine gel
      regimen found the amount of stain unacceptable and 10% noted an effect on their
      taste perception. CONCLUSIONS: The use of low dose of chlorhexidine gel at night
      and a whitening paste in the morning produced a significant amount of stain that
      30% of subjects considered unacceptable.

PMID- 17038058
TI  - Oral health in Florida nursing homes.
AB  - OBJECTIVES: The purpose of this study was to measure the oral health and hygiene
      status among 265 South Florida nursing home residents aged between 45 and 98
      years. METHODS: The oral health and hygiene status of the residents were assessed
      by noting the presence of calculus, caries, gingivitis, cheilitis, apthous ulcer,
      dry mouth and red or white lesions. RESULTS: The incidence of nursing home
      residents with calculus was 79.6% and the remaining 20.4% were edentulous. More
      than half of residents had oral problems (50.6%) the commonest was gingivitis
      (36.6%), followed by caries (26%) and tooth fracture (15.9%). Almost half the
      residents wore dentures (47.2%). Statistical analysis was conducted using
      analysis of variance (P-values). Ageing of the residents was statistically
      correlated to a worsening of oral hygiene status (P<0.0066), absence and presence
      of one or two dentures (P<0.0034) and a loss of teeth (P<0.0001). CONCLUSIONS:
      The ageing of residents is correlated to increasing oral health problems and the
      loss of teeth. Oral health neglect affects almost all of the nursing home
      residents. Care providers should receive education and training from dental
      hygienists to improve the standard of oral hygiene and health of the elderly.

PMID- 17038059
TI  - Evaluation of several brushing motion combinations in relation to plaque-removing
      efficacy with Oral-B CrossAction Power: a professional brushing study.
AB  - AIM: The aim of this study was to evaluate the additional effect of a newly
      developed battery-operated brush Oral-B CrossAction Power with a hybrid brush
      head design (CAPB). The brush combines an oscillating/rotating part, a
      PowerHead(R), with a non-moving part with CrissCross bristles. It was compared
      with a manual control toothbrush Butler GUM 311 (CTB). MATERIAL AND METHODS:
      Thirty subjects were requested not to brush their teeth 48 h prior to the
      examination, when plaque removal efficacy was assessed by scoring plaque before
      and after brushing. Plaque was assessed according to the Silness & Loe Index at
      six sites per tooth. Subjects were brushed by a dentist using one of the four
      randomly chosen procedures of brushing in each quadrant. The CAPB was used with
      three different modes of brushing each in different randomly chosen quadrants,
      with the manual toothbrush being used in the remaining quadrant as a control.
      RESULTS: The baseline plaque levels ranged from 1.69 to 1.74 and the end levels
      ranged from 0.39 to 0.45. In terms of percentage, the results with the four
      procedures run from 75% to 79%. These differences between the battery brush and
      manual brush irrespective of the brushing mode used were not statistically
      significant. CONCLUSION: The results of this Professional Brushing Study show
      that the CrossAction Power toothbrush was as effective as a regular manual
      toothbrush.

PMID- 17038060
TI  - Severe enamel abrasion due to misuse of an air polishing device.
AB  - OBJECTIVES: In this case report, a 28-year-old male patient who severely injured
      the enamel tissue of his upper incisors due to excessive self-performed air
      polishing has been presented. Air polishing devices are frequently used in
      initial or supportive periodontal therapy to remove supragingival plaque and
      dental stains. Enamel tissue is minimally affected by air polishing when
      appropriately performed by a professional. However, excessive air polishing may
      have detrimental effects even on the intact enamel. The aim of this case report
      is to present a patient who severely injured the enamel surfaces of his upper
      incisors due to excessive self-performed air polishing. METHODS: A case of severe
      enamel abrasions in a 28-year-old male patient who injured the enamel surfaces of
      his upper incisors following several self-performed air polishing sessions has
      been presented. RESULTS: Severely abraded enamel surfaces of the upper incisors
      were present and during the course of therapy restored by composite restorations
      to establish a satisfactory clinical appearance. CONCLUSIONS: In clinical
      practice, air polishing can be performed rather safely on intact enamel and is a
      beneficial procedure in initial and supportive periodontal therapy when performed
      by a professional under recommended operating conditions. However, review of the
      literature reveals that air polishing may be harmful on tooth and surrounding
      structures unless carried out cautiously. Furthermore, excessive use of air
      polishing devices, especially by unauthorized personnel may be damaging and lead
      to severe abrasion of enamel tissue.

PMID- 17038065
TI  - Dissemination of the hospital elder life program: implementation, adaptation, and
      successes.
AB  - OBJECTIVES: To describe the Hospital Elder Life Program (HELP) across
      dissemination sites, to detail adaptations, and to summarize advantages across
      sites. DESIGN: Cross-sectional survey. SETTING: HELP sites in acute care
      hospitals. PARTICIPANTS: Thirteen sites that enrolled 11,344 patients.
      MEASUREMENTS: Seventy-five closed- and open-ended questions describing details of
      the HELP site, procedures, staffing, outcomes tracked, and advantages. RESULTS:
      As of July 1, 2005, HELP had been fully implemented in 13 sites, with a median
      duration of 24 months (range 6.0-38.0). Although a high degree of fidelity to the
      original model was maintained, variations existed in staffing patterns, outcome
      tracking, and recommended HELP procedures. Adaptations were made across multiple
      domains, including enrollment criteria at 15.4% of sites, screening and
      assessment tools at 61.5%, and individual intervention protocols at 15.4% to
      30.8%. Local circumstances drove these adaptations, with the most common reasons
      being lack of adequate staffing and logistical constraints. All sites conducted
      regular HELP staff meetings; other recommended quality assurance procedures were
      conducted at 46.2% to 92.3% of sites. Reported advantages of HELP included
      providing an educational resource at 100% of sites, improving hospital outcomes
      (e.g., delirium and functional decline) at 100%, providing nursing education and
      improving retention at 100%, enhancing patient and family satisfaction with care
      at 92.3%, raising visibility for geriatrics at 92.3%, and improving quality of
      care at 84.6%. CONCLUSION: This report describes the real-world implementation of
      HELP across 13 sites, documents their local adaptations and successes, and
      provides insight into how motivated institutions can create change to improve
      quality of care for older persons.

PMID- 17038066
TI  - Community-acquired bacterial meningitis in older people.
AB  - OBJECTIVES: To describe clinical features of bacterial meningitis in older
      people. DESIGN: Cohort study. SETTING: Hospitals in the Netherlands.
      PARTICIPANTS: Patients aged over 16 with community-acquired bacterial meningitis,
      confirmed using cerebrospinal fluid culture. MEASUREMENTS: Data were collected
      prospectively. The cohort was dichotomized with respect to age (>or=60 vs 17-59).
      RESULTS: Two hundred fifty-seven of 696 episodes of community-acquired bacterial
      meningitis (37%) occurred in elderly patients and 439 (63%) in younger adults.
      Older people more often presented with the triad of fever, neck stiffness, and
      altered mental status than younger adults (58% vs 36%; P<.001). In older people,
      meningitis was due to Streptococcus pneumoniae in 176 episodes (68%). In younger
      adults, Neisseria meningitidis was the most common pathogen, responsible for 221
      episodes (50%). Elderly patients more often developed complications than younger
      adults (72% vs 57%; P<.001), which resulted in a higher mortality rate (34% vs
      13%; P<.001). Older people tended to die more often from cardiorespiratory
      failure (25% vs 11%; P=.06), whereas younger adults more often died from brain
      herniation (23% vs 2%; P=.004). CONCLUSION: Elderly patients with bacterial
      meningitis often present with classic symptoms of bacterial meningitis. Bacterial
      meningitis within this age group is predominantly due to S. pneumoniae and is
      associated with high morbidity and mortality rates. Whereas older people die
      frequently of cardiorespiratory failure, younger adults more often die of brain
      herniation.

PMID- 17038067
TI  - Use of selective serotonin reuptake inhibitors and sleep disturbances in
      community-dwelling older women.
AB  - OBJECTIVES: To determine the association between use of selective serotonin
      reuptake inhibitors (SSRIs) and objective measures of sleep disturbances in older
      community-dwelling women, including women without evidence of depression. DESIGN:
      Cross-sectional study. SETTING: Four U.S. clinical centers. PARTICIPANTS: Two
      thousand eight hundred fifty-three women aged 71 and older (2,630 nonusers of
      antidepressants and 223 taking SSRIs alone, not in combination with other
      antidepressants). MEASUREMENTS: Medication use, assessed using an interviewer
      administered questionnaire with verification of use from medication containers
      and computerized dictionary used to categorize type of medication; evidence of
      depression assessed using self-report or a score of 6 or higher on the Geriatric
      Depression Scale; and sleep parameters measured using a wrist actigraph, with
      data collected for an average of four consecutive 24-hour periods. RESULTS: Of
      the overall cohort of 2,853 women and of 2,337 women without evidence of
      depression, sleep disturbances were more common in women taking SSRIs than in
      those not taking antidepressants. After excluding women with evidence of
      depression and adjusting for multiple potential confounders, women taking SSRIs
      were more likely to have a sleep duration of 5 hours or less (multivariate odds
      ratio (MOR)=2.15, 95% confidence interval (CI)=1.04-4.47), sleep efficiency less
      than 70% (MOR=2.37, 95% CI=1.32-4.25), sleep latency of 1 hour or more (MOR=3.99,
      95% CI=2.29-6.96) and eight or more long wake episodes (MOR=1.75, 95% CI=0.99
      3.10). CONCLUSION: SSRI use by older women, including those without evidence of
      depression, is associated with a greater likelihood of sleep disturbances,
      including poorer sleep efficiency, longer sleep latency, and sleep fragmentation,
      manifested by multiple long wake episodes. These results add to the uncertainty
      regarding risks and benefits of SSRI use in aged populations.

PMID- 17038068
TI  - Polypharmacy and prescribing quality in older people.
AB  - OBJECTIVES: To evaluate the relationship between inappropriate prescribing,
      medication underuse, and the total number of medications used by patients.
      DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center.
      PARTICIPANTS: One hundred ninety-six outpatients aged 65 and older who were
      taking five or more medications. MEASUREMENTS: Inappropriate prescribing was
      assessed using a combination of the Beers drugs-to-avoid criteria (2003 update)
      and subscales of the Medication Appropriateness Index that assess whether a drug
      is ineffective, not indicated, or unnecessary duplication of therapy. Underuse
      was assessed using the Assessment of Underutilization of Medications instrument.
      All vitamins and minerals, topical and herbal medications, and medications taken
      as needed were excluded from the analyses. RESULTS: Mean age was 74.6, and
      patients used a mean+/-standard deviation of 8.1+/-2.5 medications (range 5-17).
      Use of one or more inappropriate medications was documented in 128 patients
      (65%), including 73 (37%) taking a medication in violation of the Beers drugs-to
      avoid criteria and 112 (57%) taking a medication that was ineffective, not
      indicated, or duplicative. Medication underuse was observed in 125 patients
      (64%). Together, inappropriate use and underuse were simultaneously present in 82
      patients (42%), whereas 25 (13%) had neither inappropriate use nor underuse. When
      assessed by the total number of medications taken, the frequency of inappropriate
      medication use rose sharply from a mean of 0.4 inappropriate medications in
      patients taking five to six drugs, to 1.1 inappropriate medications in patients
      taking seven to nine drugs, to 1.9 inappropriate medications in patients taking
      10 or more drugs (P<.001). In contrast, the frequency of underuse averaged 1.0
      underused medications per patient and did not vary with the total number of
      medications taken (P=.26). Overall, patients using fewer than eight medications
      were more likely to be missing a potentially beneficial drug than to be taking a
      medication considered inappropriate. CONCLUSION: Inappropriate medication use and
      underuse were common in older people taking five or more medications, with both
      simultaneously present in more than 40% of patients. Inappropriate medication use
      is most frequent in patients taking many medications, but underuse is also common
      and merits attention regardless of the total number of medications taken.

PMID- 17038069
TI  - The epidemiology of bathing disability in older persons.
AB  - OBJECTIVES: To quantify the burden of bathing disability over time; to determine
      whether the burden of bathing disability differs according to age, sex, and
      physical frailty; and to evaluate the relationship between disability in bathing
      and disability in other essential activities of daily living (ADLs). DESIGN:
      Prospective cohort study. SETTING: General community in greater New Haven,
      Connecticut. PARTICIPANTS: Seven hundred fifty-four community-living older
      persons aged 70 and older who were nondisabled (required no personal assistance)
      in four essential ADLs: bathing, dressing, transferring from a chair, and walking
      inside the house. MEASUREMENTS: Bathing disability, defined as the inability to
      wash and dry one's whole body without personal assistance, was assessed every
      month for up to 6 years, along with disability in dressing, transferring, and
      walking. RESULTS: Over the course of 6 years, 440 participants (58.4%) had at
      least one episode of bathing disability, and 266 (34.0%) had multiple episodes,
      with the duration of each episode averaging about 6 months. Whether assessed as
      number of episodes, duration of episodes, incidence rates, or number of months
      per 100 months, the burden of bathing disability was greatest in participants who
      were physically frail and was consistently higher in women than men and in
      participants who were aged 80 and older than those who were aged 70 to 79. Most
      episodes of bathing disability (86.1%) were not preceded in the prior month by
      disability in dressing, transferring, or walking, and nearly half (48.3%) were
      not accompanied at onset by disability in one or more of these other ADLs. In a
      multivariable model that included age, sex, and physical frailty, the onset of
      bathing disability increased the likelihood of developing disability in the other
      essential ADLs the following month fivefold (hazard ratio=5.1, 95% confidence
      interval=4.1-6.4). CONCLUSION: Disability in bathing may serve as a sentinel
      event in the disabling process. Given the recurrent nature of bathing disability,
      programs designed to enhance independent bathing will need to focus not only on
      the prevention of bathing disability, but also on the restoration and maintenance
      of independent bathing in older persons who become disabled.

PMID- 17038070
TI  - Diagnosis and characteristics of syncope in older patients referred to geriatric
      departments.
AB  - OBJECTIVES: To test the applicability and safety of a standardized diagnostic
      algorithm in geriatric departments and to define the prevalence of different
      causes of syncope in older patients. DESIGN: Multicenter cross-sectional
      observational study. SETTING: In-hospital geriatric acute care departments and
      outpatient clinics. PARTICIPANTS: Two hundred forty-two patients (aged>or=65,
      mean+/-standard deviation=79+/-7, range 65-98) consecutively referred for
      evaluation of transient loss of consciousness to any of six clinical centers
      participating in the study. Of these, 11 had a syncope-like condition (5
      transient ischemic attack; 6 seizures), and 231 had syncope (aged 65-74, n=71;
      aged>or=75, n=160). MEASUREMENTS: Protocol designed to define etiology and
      clinical characteristics of syncope derived from European Society of Cardiology
      Guidelines on syncope. RESULTS: No major complication occurred with use of the
      protocol. Neurally mediated was the more prevalent form of syncope in this
      population (66.6%). Cardiac causes accounted for 14.7% of all cases. The
      neuroreflex form of syncope (vasovagal, situational, and carotid sinus syndrome)
      was more common in younger than in older patients (62.3% vs 36.2%; P=.001),
      whereas orthostatic syncope was more frequent in the older than in the younger
      group (30.5% vs 4.2%; P<.001). In only 10.4% of cases, syncope remained of
      unexplained origin. After initial evaluation, a definite diagnosis was possible
      in 40.1% of the cases, and a suspected diagnosis was obtained in 57.9%. Syncope
      of suspected cardiac origin after initial evaluation was confirmed in 43.7% of
      cases, and neuromediated causes were confirmed in 83.5% of the cases. CONCLUSION:
      The protocol is applicable even beyond the age of 90 in geriatric departments.
      The standardized protocol is associated with a reduction in the frequency of
      unexplained syncope to about 10%.

PMID- 17038071
TI  - Clinical features of reflux esophagitis in older people: a study of 840
      consecutive patients.
AB  - OBJECTIVES: To compare symptoms and other clinical characteristics of reflux
      esophagitis in patients of different ages. DESIGN: Observational cross-sectional
      study of consecutive patients. SETTING: Geriatric Unit, Casa Sollievo della
      Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico.
      PARTICIPANTS: Eight hundred forty patients with endoscopically diagnosed erosive
      esophagitis divided into four groups according to age (young (<50, mean 36.7,
      n=114), adult (50-69, mean 59.1, n=126), elderly (70-84, mean 77.3, n=425), and
      very elderly (>or=85, mean 88.4, n=175)). MEASUREMENTS: Gastrointestinal symptoms
      were evaluated using the Gastrointestinal Symptom Rating Scale questionnaire.
      Other symptoms were recorded when present as an indication for endoscopy.
      Severity of esophagitis, presence of Helicobacter pylori infection, presence and
      size of hiatus hernia, Barrett's esophagus, antrum or corpus gastric atrophy, and
      nonsteroidal antiinflammatory drug (NSAID) use were also evaluated. RESULTS:
      Elderly and very elderly patients had a significantly lower prevalence of typical
      gastroesophageal reflux disease symptoms (heartburn or acid regurgitation
      (P<.001) and epigastric pain (P<.001)) than young and adult patients. Conversely,
      the prevalence of other symptoms (anorexia (P<.001), weight loss (P<.007), anemia
      (P<.001), vomiting (P<.001), and dysphagia (P<.001)) significantly increased with
      age. The prevalence of severe esophagitis (P<.001), hiatus hernia (P<.005), the
      size of hiatus hernia (P<.001), antrum and corpus gastric atrophy (P<.05) and
      NSAID use (P<.005) also significantly increased with age. Multivariate analysis
      demonstrated that older age (65-84, odds ratio (OR)=2.66, 95% confidence interval
      (CI)=1.38-5.12; >or=85, OR=4.57, 95% CI=2.15-9.71), hiatus hernia larger than 3
      cm in diameter (OR=2.38, 95% CI=1.41-4.01), and male sex (OR=2.83, 95% CI=1.72
      4.64) are independent risk factors for severe esophagitis, whereas H. pylori
      infection, gastric atrophy, NSAID use, and the presence of hiatus hernia were
      not. CONCLUSION: Elderly patients with reflux esophagitis had less-typical and
      more-nonspecific symptoms than young or adult patients. Old age, male sex, and
      hiatus hernia size greater than 3 cm are significantly associated with severe
      esophagitis. Clinicians caring for older patients should be aware of the
      nonspecific presentation and potential severity of reflux esophagitis in this
      population.

PMID- 17038072
TI  - Over-the-counter drug use by medicare beneficiaries in nursing homes:
      implications for practice and policy.
AB  - OBJECTIVES: To examine over-the-counter (OTC) medication use by Medicare
      beneficiaries in nursing homes and to assess evidence of substitution of OTC
      medications for prescription (Rx) medications by residents with no Rx coverage
      and Medicaid. DESIGN: Cross-sectional multivariable analysis. SETTING: Medicare
      beneficiaries included in the nationally representative Medicare Current
      Beneficiary Survey in 2001. PARTICIPANTS: Seven hundred eighty-nine Medicare
      beneficiaries with 1 or more months in a nursing home. MEASUREMENTS: Proportions
      of residents using Rx and OTC medications per resident-month and counts of drugs
      used within selected therapeutic classes. RESULTS: Study subjects were high users
      of Rx (98%) and OTC (94%) drugs. The average resident was administered 8.8 unique
      medications per month (5.9 Rx and 2.9 OTC medications). Twelve therapeutic
      classes accounted for 93.9% of OTC medication use by residents, but Rx use was
      also high in some of these same classes. For example, 70.3% of all subjects used
      nonopioid OTC analgesics, and 19.0% used nonopioid Rx analgesics, and 13.8% used
      OTC antacids/antiulcer agents, whereas 35.8% used Rx products in this class. The
      highest overlap was in the category of cough and cold medications, of which 19.3%
      used OTCs and 20.1% used Rx drugs. Multivariate regression analyses applied to
      users of drugs in each these three therapeutic classes found no evidence that Rx
      coverage influenced the choice of OTC versus Rx-only medications. CONCLUSION:
      OTCs represent an important component of the therapeutic regimens of nursing home
      residents, but utilization rates are insensitive to drug coverage. That may
      change with the implementation of the Medicare Part D drug benefit.

PMID- 17038074
TI  - Age-related macular degeneration: self-management and reduction of depressive
      symptoms in a randomized, controlled study.
AB  - OBJECTIVES: To assess the effectiveness of a self-management program for age
      related macular degeneration (AMD) in reducing depressive symptoms. DESIGN:
      Analysis of 6-month follow-up for a subset of participants in a randomized,
      controlled trial who were clinically depressed at baseline. SETTING: University
      ophthalmology clinic. PARTICIPANTS: Thirty-two depressed older adult volunteers
      (mean age 81.5) with advanced AMD who had been randomized to a self-management
      program (n=12) or one of two control conditions (n=20). Subjects were included if
      at baseline they met criteria from the Structured Clinical Interview for the
      Diagnostic and Statistical Manual of Mental Disorders, Axis, I, Fourth Edition,
      Research Version, for major or minor depressive disorder with significant
      depressive symptoms (>or=5 points) on the 15-item Geriatric Depression Scale (GDS
      15). INTERVENTION: AMD self-management program consisting of cognitive and
      behavioral elements including health education and enhancement of problem-solving
      skills. MEASUREMENTS: Primary outcome measure was GDS-15. Secondary outcome
      measures included National Eye Institute Visual Function Questionnaire (NEI-VFQ)
      and AMD Self-Efficacy Questionnaire. RESULTS: At 6-month follow-up, the self
      management group had a significantly greater reduction in depressive symptoms on
      the GDS-15 than the controls (P=.03). The mean reduction of 2.92 points in the
      self-management group was more than the 2-point change threshold considered to be
      clinically meaningful. Change on the NEI-VFQ was nonsignificant. Reduction in
      depressive symptoms was associated with greater self-efficacy in the self
      management group. CONCLUSION: These findings may support the effectiveness of an
      AMD self-management program for depressed older adults with advanced vision loss
      from AMD.

PMID- 17038073
TI  - Reducing suicidal ideation in depressed older primary care patients.
AB  - OBJECTIVES: To determine the effect of a primary care-based collaborative care
      program for depression on suicidal ideation in older adults. DESIGN: Randomized,
      controlled trial. SETTING: Eighteen diverse primary care clinics. PARTICIPANTS:
      One thousand eight hundred one adults aged 60 and older with major depression or
      dysthymia. INTERVENTION: Participants randomized to collaborative care had access
      to a depression care manager who supported antidepressant medication management
      prescribed by their primary care physician and offered a course of Problem
      Solving Treatment in Primary Care for 12 months. Participants in the control arm
      received care as usual. MEASUREMENTS: Participants had independent assessments of
      depression and suicidal ideation at baseline and 3, 6, 12, 18, and 24 months.
      Depression was assessed using the Structured Clinical Interview for the
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID).
      Suicidal ideation was determined using the SCID and the Hopkins Symptoms
      Checklist. RESULTS: At baseline, 139 (15.3%) intervention subjects and 119
      (13.3%) controls reported thoughts of suicide. Intervention subjects had
      significantly lower rates of suicidal ideation than controls at 6 months (7.5% vs
      12.1%) and 12 months (9.8% vs 15.5%) and even after intervention resources were
      no longer available at 18 months (8.0% vs 13.3%) and 24 months (10.1% vs 13.9%).
      There were no completed suicides in either group. Information on suicide attempts
      or hospitalization for suicidal ideation was not available. CONCLUSION: Primary
      care-based collaborative care programs for depression represent one strategy to
      reduce suicidal ideation and potentially the risk of suicide in older primary
      care patients.

PMID- 17038075
TI  - To what extent do geriatricians document the most bothersome symptoms of patients
      with advanced dementia?
AB  - OBJECTIVES: To assess whether geriatricians documented the bothersome symptoms of
      patients with advanced dementia, proxy reports of the most-bothersome symptoms
      affecting those patients (as elicited in research interviews) were compared with
      what geriatricians who had seen those patients in a proximate clinic visit
      documented in the medical record. DESIGN: Retrospective chart review. SETTING:
      Outpatient geriatrics clinic at the University of Chicago. PARTICIPANTS: Fifty
      seven pairs of patients with dementia (Functional Assessment Staging Tool stage 6
      or 7) and their proxies. MEASUREMENTS: Clinic notes were reviewed for
      documentation of patients' bothersome symptoms that proxies reported during
      research interviews. Proxy reports had been recorded in the previously
      established Palliative Excellence in Alzheimer Care Efforts database. RESULTS:
      The most-bothersome symptom was documented at least once in 84.2% (48/57) of
      clinic notes. The second-most-bothersome symptom was documented in 70.3% (26/37)
      of clinic notes. Most symptoms were documented in the Assessment and Plan section
      of the note. CONCLUSION: Geriatricians identified and documented the vast
      majority of bothersome symptoms, as reported by proxies, of patients with
      moderate to severe dementia.

PMID- 17038076
TI  - Satisfaction with end-of-life care for nursing home residents with advanced
      dementia.
AB  - OBJECTIVES: To identify factors associated with satisfaction with care for
      healthcare proxies (HCPs) of nursing home (NH) residents with advanced dementia.
      DESIGN: Cross-sectional study. SETTING: Thirteen NHs in Boston. PARTICIPANTS: One
      hundred forty-eight NH residents aged 65 and older with advanced dementia and
      their formally designated HCPs. MASUREMENTS: The dependent variable was HCPs'
      score on the Satisfaction With Care at the End of Life in Dementia (SWC-EOLD)
      scale (range 10-40; higher scores indicate greater satisfaction). Resident
      characteristics analyzed as independent variables were demographic information,
      functional and cognitive status, comfort, tube feeding, and advance care
      planning. HCP characteristics were demographic information, health status, mood,
      advance care planning, and communication. Multivariate stepwise linear regression
      was used to identify factors independently associated with higher SWC-EOLD score.
      RESULTS: The mean ages+/-standard deviation of the 148 residents and HCPs were
      85.0+/-8.1 and 59.1+/-11.7, respectively. The mean SWC-EOLD score was 31.0+/-4.2.
      After multivariate adjustment, variables independently associated with greater
      satisfaction were more than 15 minutes discussing advance directives with a care
      provider at the time of NH admission (parameter estimate=2.39, 95% confidence
      interval (CI)=1.16-3.61, P<.001), greater resident comfort (parameter
      estimate=0.10, 95% CI=0.02-0.17, P=.01), care in a specialized dementia unit
      (parameter estimate=1.48, 95% CI=0.25-2.71, P=.02), and no feeding tube
      (parameter estimate=2.87, 95% CI=0.46-5.25, P=.02). CONCLUSION: Better
      communication, greater resident comfort, no tube feeding, and care in a
      specialized dementia unit are modifiable factors that may improve satisfaction
      with care in advanced dementia.

PMID- 17038077
TI  - Cariogenic bacteria and caries risk in elderly Japanese aged 80 and older with at
      least 20 teeth.
AB  - OBJECTIVES: To assess caries risk and check the presence of four commonly found
      oral cariogenic bacteria in "8020" achievers. DESIGN: Initial report based on
      Japan's newly implemented "8020" campaign, which aims to promote health and
      awareness in older people. Simply stated, the goal is, at 80 years, to maintain
      20 teeth. SETTING: Healthy community-dwelling elderly individuals of Okayama
      Prefecture, Japan. PARTICIPANTS: One hundred sixty individuals aged 80 and older
      with 20 of their own natural teeth. MEASUREMENTS: General and oral health
      conditions, caries risk assessment using the Cariostat method, and polymerase
      chain reaction (PCR) detection of four oral cariogenic bacteria. RESULTS: The
      participants had an average of 24.7 teeth, of which 12.1 were sound, 12.2 were
      treated, and 0.4 were untreated. Based on Cariostat scores, 64.4% had low caries
      risk. Using PCR, Streptococcus mutans, S. sobrinus, Lactobacillus casei, and L.
      plantarum were detected in 51.3%, 23.1%, 40%, and 25% of the participants,
      respectively. S. mutans (P<.001), S. sobrinus (P=.002), L. casei (P<.001), and L.
      plantarum (P=.001) deoxyribonucleic acid band was detected more in participants
      with high caries risk scores. CONCLUSION: Participants with low caries risk
      scores had low prevalence of cariogenic bacteria, 20 or more sound teeth, and
      fewer missing teeth. Incorporating caries risk assessment, using the Cariostat
      and PCR analysis, in the "8020" campaign in health systems worldwide will
      contribute to a better life for the aging society, initiate research interest
      regarding the program, and improve current health policies.

PMID- 17038078
TI  - Preoperative risk assessment for delirium after noncardiac surgery: a systematic
      review.
AB  - Delirium is a common postoperative complication in older adults associated with
      adverse events including functional decline, longer lengths of stay, and risk of
      institutionalization. The purpose of this article is to systematically review
      preoperative risk factors associated with delirium following noncardiac surgery.
      A medical literature search was conducted using several bibliographic databases
      (PubMed, CINAHL, Cochrane, PsychInfo), supplemented by a manual search of the
      references of retrieved articles. Studies were retained for review after meeting
      strict inclusion criteria that included only operative patients with incident
      postoperative delirium diagnosed prospectively using criteria derived from the
      Diagnostic and Statistical Manual of Mental Disorders Third or Fourth Edition.
      Quantitative analyses included significance testing, homogeneity testing, and
      effect-size pooling. Twenty-five articles were included for review. The incidence
      of delirium ranged from 5.1% to 52.2%, with greater rates after hip fracture and
      aortic surgeries. This review found two scales, a clinical prediction rule, and a
      delirium risk classification system that were validated in other operative
      settings. Individual risk factor analysis suggested that cognitive impairment,
      older age, functional impairment, sensory impairment, depression, preoperative
      psychotropic drug use, psychopathological symptoms, institutional residence, and
      greater comorbidity were associated with postoperative delirium. Of the risk
      factors examined, evidence was most robust for an association between delirium
      and cognitive impairment or psychotropic drug use, with moderate effect sizes for
      both. Missing data and measurement differences did not allow for inferences to be
      made about other risk factors. Effect-size pooling supports the concept that
      delirium is a heterogeneous disorder with multiple risk factors. More research is
      needed to better identify patients at risk for postoperative delirium and to
      develop preventive strategies.

PMID- 17038079
TI  - Traumatic brain injury in older adults: epidemiology, outcomes, and future
      implications.
AB  - Traumatic brain injury (TBI) is a significant problem in older adults. In persons
      aged 65 and older, TBI is responsible for more than 80,000 emergency department
      visits each year; three-quarters of these visits result in hospitalization as a
      result of the injury. Adults aged 75 and older have the highest rates of TBI
      related hospitalization and death. Falls are the leading cause of TBI for older
      adults (51%), and motor vehicle traffic crashes are second (9%). Older age is
      known to negatively influence outcome after TBI. Although geriatric and
      neurotrauma investigators have identified the prognostic significance of
      preadmission functional ability, comorbidities, sex, and other factors such as
      cerebral perfusion pressure on recovery after illness or injury, these variables
      remain understudied in older adults with TBI. In the absence of good clinical
      data, predicting outcomes and providing care in the older adult population with
      TBI remains problematic. To address this significant public health issue, a
      refocusing of research efforts on this population is justified to prevent TBI in
      the older adult and to discern unique care requirements to facilitate best
      patient outcomes.

PMID- 17038080
TI  - Clinical characteristics and longitudinal changes of informal cost of Alzheimer's
      disease in the community.
AB  - Most estimates of the cost of informal caregiving in patients with Alzheimer's
      disease (AD) remain cross-sectional. Longitudinal estimates of informal
      caregiving hours and costs are less frequent and are from assessments covering
      only short periods of time. The objectives of this study were to estimate long
      term trajectories of the use and cost of informal caregiving for patients with AD
      and the effects of patient characteristics on the use and cost of informal
      caregiving. The sample is drawn from the Predictors Study, a large, multicenter
      cohort of patients with probable AD, prospectively followed annually for up to 7
      years in three university-based AD centers in the United States (n=170).
      Generalized linear mixed models were used to estimate the effects of patient
      characteristics on use and cost of informal caregiving. Patients' clinical
      characteristics included cognitive status (Mini-Mental State Examination),
      functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities,
      psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal
      signs. Results show that rates of informal care use and caregiving hours (and
      costs) increased substantially over time but were related differently to
      patients' characteristics. Use of informal care was significantly associated with
      worse cognition, worse function, and higher comorbidities. Conditional on
      receiving informal care, informal caregiving hours (and costs) were mainly
      associated with worse function. Each additional point on the BDRS increased
      informal caregiving costs 5.4%. Average annual informal cost was estimated at
      $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4.

PMID- 17038081
TI  - Are internal medicine residency programs adequately preparing physicians to care
      for the baby boomers? A national survey from the Association of Directors of
      Geriatric Academic Programs Status of Geriatrics Workforce Study.
AB  - Patients aged 65 and older account for 39% of ambulatory visits to internal
      medicine physicians. This article describes the progress made in training
      internal medicine residents to care for older Americans. Program directors in
      internal medicine residency programs accredited by the Accreditation Council for
      Graduate Medical Education were surveyed in the spring of 2005. Findings from
      this survey were compared with those from a similar 2002 survey to determine
      whether any changes had occurred. A 60% response rate was achieved (n=235). In
      these 3-year residency training programs, 20 programs (9%) required less than 2
      weeks of clinical instruction that was specifically structured to teach geriatric
      care principles, 48 (21%) at least 2 weeks but less than 4 weeks, 144 (62%) at
      least 4 weeks but less than 6 weeks, and 21 (9%) required 6 or more weeks. As in
      2002, internal medicine residency programs continue to depend on nursing home
      facilities, geriatric preceptors in nongeriatric clinical ambulatory settings,
      and outpatient geriatric assessment centers for their geriatrics training.
      Training was most often offered in a block format. The mean number of physician
      faculty per residency program dedicated to teaching geriatric medicine was 3.5
      full-time equivalents (FTEs) (range 0-50), compared with a mean of 2.2 FTE
      faculty in 2002 (P<or=.001). Internal medicine educators are continuing to
      improve the training of residents so that, as they become practicing physicians,
      they will have the knowledge and skills in geriatric medicine to care for older
      adults.

PMID- 17038082
TI  - Continuing medical education, continuing professional development, and knowledge
      translation: improving care of older patients by practicing physicians.
AB  - Many community-based internists and family physicians lack familiarity with
      geriatrics knowledge and best practices, but they face overwhelming fiscal and
      time barriers to expanding their skills and improving their behavior in the care
      of older people. Traditional lecture-and-slide-show continuing medical education
      (CME) programs have been shown to be relatively ineffective in changing this
      target group's practice. The challenge for geriatrics educators, then, is to
      devise CME programs that are highly accessible to practicing physicians, that
      will have an immediate and significant effect on practitioners' behavior, and
      that are financially viable. Studies of CME have shown that the most effective
      programs for knowledge translation in these circumstances involve what is known
      as active-mode learning, which relies on interactive, targeted, and multifaceted
      techniques. A systematic literature review, supplemented by structured
      interviews, was performed to inventory active-mode learning techniques for
      geriatrics knowledge and skills in the United States. Thirteen published articles
      met the criteria, and leaders of 28 active-mode CME programs were interviewed.
      This systematic review indicates that there is a substantial experience in
      geriatrics training for community-based physicians, much of which is unpublished
      and incompletely evaluated. It appears that the most effective methods to change
      behaviors involved multiple educational efforts such as written materials or
      toolkits combined with feedback and strong communication channels between
      instructors and learners.

PMID- 17038083
TI  - Staphylococcus hemolyticus liver abscess as an uncommon presentation of silent
      colonic cancer: a case report.

PMID- 17038084
TI  - Paralytic ileus after discontinuation of cholinesterase inhibitor.

PMID- 17038085
TI  - Is there really hope for the future? Geriatrics and palliative care.

PMID- 17038086
TI  - Unmet activity of daily living needs: elder mistreatment and ethics in geriatric
      research.

PMID- 17038088
TI  - Normal homocysteine levels in well-functioning oldest-old individuals despite low
      kidney function.

PMID- 17038089
TI  - Electronic versus paper-based nursing documentation systems: the caregivers weigh
      in.

PMID- 17038090
TI  - Importance of assistance by caregivers for inhaled corticosteroid therapy in
      elderly patients with asthma.

PMID- 17038091
TI  - Visual hallucination and temazepam: an unusual case.

PMID- 17038092
TI  - Geriatrics.

PMID- 17038094
TI  - Editorial: the evidence for evidence-based practice.

PMID- 17038095
TI  - Handling of peripheral intravenous cannulae: effects of evidence-based clinical
      guidelines.
AB  - AIM: This study aimed at evaluating the outcome of implemented evidence-based
      clinical guidelines by means of surveying the frequency of thrombophlebitis,
      nurses' care, handling and documentation of peripheral intravenous cannulae.
      BACKGROUND: Peripheral intravenous cannulae are frequently used for vascular
      access and, thereby, the patients will be exposed to local and systemic
      infectious complications. Evidence-based knowledge of how to prevent these
      complications and how to care for patients with peripheral intravenous cannula is
      therefore of great importance. Deficient care, handling and documentation of
      peripheral intravenous cannulae have previously been reported. DESIGN: A cross
      sectional survey was conducted by a group of nurses at three wards at a
      university hospital before and after the implementation of the evidence-based
      guidelines. METHOD: A structured observation protocol was used to review the
      frequency of thrombophlebitis, the nurses' care, handling and the documentation
      of peripheral intravenous cannulae in the patient's record. RESULTS: A total of
      107 and 99 cannulae respectively were observed before and after the
      implementation of the guidelines. The frequency of peripheral intravenous
      cannulae without signs of thrombophlebitis increased by 21% (P < 0.01) and the
      use of cannula size 0.8 mm increased by 22% (P < 0.001). Nurses' documentation of
      peripheral intravenous cannula improved significantly (P < 0.001). CONCLUSION: We
      conclude that implementation of the guidelines resulted in significant
      improvements by means of decreased frequency of signs of thrombophlebitis,
      increased application of smaller cannula size (0.8 mm), as well as of the nurses'
      documentation in the patient's record. RELEVANCE TO CLINICAL PRACTICE: Further
      efforts to ameliorate care and handling of peripheral intravenous cannulae are
      needed. This can be done by means of increasing nurses' knowledge and recurrent
      quality reviews. Well-informed patients can also be more involved in the care
      than is common today.

PMID- 17038096
TI  - A new research agenda: improving health care in general hospitals.
AB  - AIM AND OBJECTIVES: To set out the research required to improve the health of
      people with learning disabilities in general hospital settings. The objectives
      are: (i) to share service developments in a mapping exercise to provide a picture
      of current work in this area, and (ii) to identify practice issues and
      experiences that can contribute to a broader research agenda. BACKGROUND: It is
      recognized that people with learning disabilities are high users of all
      healthcare systems and have different pattern of health needs that often go
      unidentified, with some requiring general hospital care. The research evidence
      base in this area of practice needs to be developed to promote and improve health
      care. METHOD: A facilitated focus group design was employed at a conference event
      to identify areas for research in the future and determined that action is
      required on four broad research fronts. RESULTS: Research is required to
      establish core principles of care, service developments, practical care measures
      and influencing change in practice. CONCLUSION: Research collaborations need to
      be established to support activity in this area and requires action in the
      future. RELEVANCE TO CLINICAL PRACTICE: The evidence base and understanding of
      the high and differing pattern of health needs of people with learning
      disabilities continues to evolve and develop, with considerable scope to identify
      new areas for research. A conference approach was used to identify research
      questions to improve the care of this group in general hospital settings and
      offers a model that may be helpful in defining new areas of enquiry in the
      future.

PMID- 17038097
TI  - Knowledge and attitudes of medical, nursing, dentistry and health technician
      students towards organ donation: a pilot study.
AB  - AIM: This pilot study assesses the knowledge and attitudes of medicine, nursing,
      dentistry and health technical students toward organ donation. BACKGROUND:
      Medicine, nursing, dentistry and health technical students' knowledge of and
      attitudes towards organ donation may be a factor in organ procurement rates.
      There is a lack of information about how Turkish medicine, nursing, dentistry and
      health technical students perceive organ donation, and what they know about it.
      METHOD: Students completed a self-administered questionnaire after a lecture. The
      questionnaire included a test that was used to assess knowledge of and attitudes
      about organ donation. RESULTS: Of the students, 56.8% were men, 91.4% were 18-24
      year old and 89.4% from east region of Turkey. Of students, 65.5% were willing,
      9% were not willing, 25.5% were hesitant about organ donation and 6% of willing
      students reported carrying a signed card. The most common reason for
      unwillingness to organ donation was worries about illegal behaviours (2.4%).
      There was a statistical relationship between willingness of students for organ
      donation and gender but were not any statistical relationship between willingness
      of students for organ donation and age, school, region and recognizing relatives
      whose need organ transplantation. Majority of the students listed transplantable
      organs truly but 63.1% were had no idea about organ donation process. CONCLUSION:
      Students' had a lack of information about organ donation. The results of this
      study support a greater emphasis on providing information regarding
      transplantation in medicine, nursing, dentistry and health technical schools to
      improve the knowledge of future heath care professionals about transplantation
      and organ donation issues. RELEVANCE TO CLINICAL PRACTICE: These findings
      highlight a need to review these schools' curricula and emphasize the importance
      of organ transplantation. This strategy may be part of the solution to the
      chronic shortage of donor organs for transplantation.

PMID- 17038098
TI  - Nurses' perceptions of their documentation experiences in a computerized nursing
      care planning system.
AB  - AIM: To explore how the content design of a computerized nursing care plan
      affects nurses' perceptions of their documentation experience, specifically in
      making care plans. BACKGROUND: Nurses' attitudes towards and experiences of
      computer use in daily practice have been studied. However, no studies have
      examined how using a computerized nursing care planning system affects nurses'
      perceptions of the documentation process. METHODS: A descriptive, exploratory
      qualitative approach was used to conduct one-on-one, in-depth interviews with 20
      nurses. The major interview question was, 'What do you think the content of the
      computerized care plan provided in making care plans?' Data analysis was based on
      Miles and Huberman's data reduction, data display, and a conclusion verification
      process. FINDINGS: Nurses generally viewed the content of the computerized
      nursing care planning system as a reference to aid memory, a learning tool for
      patient care, and a vehicle for applying judgement to modify care plan content.
      CONCLUSIONS: Although computer technology is designed to streamline nurses' work,
      using a computerized care plan system can also enhance their knowledge,
      experience and judgement of descriptions of patient problems and care strategies.
      Thus, the effects of using technology on documentation behaviours or patterns may
      deserve further exploration. RELEVANCE TO CLINICAL PRACTICE: While computerized
      documentation systems have been used widely in patient care, little attention has
      been given to how the design of care plan content affects the documentation
      process. Electronic documentation systems can introduce nurses to new skills and
      knowledge that may improve care quality.

PMID- 17038099
TI  - Brief interventions for high-risk drinkers.
AB  - AIMS AND OBJECTIVES: The purpose of this paper is to explore the literature on
      brief alcohol intervention and to review the literature that examines the status
      of the clinic nurse in the delivery of these interventions. The objective is to
      review critically the literature on brief intervention to create links for nurse
      developed and delivered brief intervention to high-risk drinkers. BACKGROUND:
      Population estimates suggest that more than one-third of North Americans drink
      excessively with even higher rates for individuals treated in primary care
      settings. Alcohol use has been identified as the third leading cause of mortality
      in the United States. This problem is not unique to the US and, worldwide,
      agencies and governmental offices and ministries have issued recommendations to
      screen patients for alcohol misuse and deliver brief interventions to individuals
      considered to be high-risk drinkers. Numerous randomized controlled trials and
      recent meta-analyses have supported the use of screening and brief intervention
      for reducing alcohol consumption in primary healthcare settings. The vast
      majority of studies reporting on brief interventions have focused on the role of
      the physician with minimal if any involvement of the clinic nurse. A scant number
      of studies have been conducted that define and assess the role or potential role
      of the clinic nurse in providing screening and brief intervention to high-risk
      drinkers in the primary care setting. METHODS: Systematic review. RESULTS: Six
      systematic reviews and meta-analyses from an international base of studies
      support the use of brief intervention in the primary care setting. Three
      randomized control trials have highlighted the role of the staff or clinic nurse
      but there are no meta-analyses addressing nurse-delivered brief interventions.
      Numerous studies have explored factors effecting the implementation of brief
      intervention into the primary care setting. CONCLUSION: Brief intervention is
      recognized as a legitimate nursing role but little has been done to develop and
      define the role of the nurse in delivering brief interventions to high-risk
      drinkers. This represents a major lacuna in both the nursing and alcoholism
      literature, where only a handful of studies have investigated nurse-delivered
      brief intervention. RELEVANCE TO CLINICAL PRACTICE: As health screening and
      health promotion are hallmarks of nursing care, nurses need to explore the use of
      brief intervention in their daily practice.

PMID- 17038100
TI  - The meaning of living with dementia and disturbing behaviour as narrated by three
      persons admitted to a residential home.
AB  - AIM: The aim of our study was to illuminate the meaning of living with dementia
      and disturbing behaviour, as narrated by three persons admitted to a residential
      home. BACKGROUND: Living with dementia and so-called disturbing behaviour in an
      institution involves interaction with care providers and fellow residents and
      poses a challenge to all who are involved. METHODS: We asked the head nurses at a
      residential home to select persons with dementia and disturbing behaviour who
      were willing to be interviewed and able to communicate verbally. We performed 10
      informal conversational interviews with three persons. The interviews were
      transcribed into text and interpreted using a phenomenological hermeneutic method
      inspired by Ricoeur's philosophy. RESULTS: The findings indicate that the meaning
      of living with dementia and disturbing behaviour, as narrated by three persons
      admitted to a residential home, is about being surrounded by disorder, being
      trapped by restriction and being set aside, as well as about being included. The
      findings are interpreted as a collapse of relations to self and others
      intertwined with occasional episodes of togetherness. This is reflected on in
      relation to the literature on homelessness and at-homeness and loss and
      maintenance of personal and social selves. RELEVANCE TO CLINICAL PRACTICE: The
      view others have of the person with dementia and of disturbing behaviour
      determines the nursing care given. Taking the residents' personal history and
      actual context into account, disturbing behaviour may be seen as a way persons
      with dementia express their story and maintain their self.

PMID- 17038101
TI  - Avoidance of solid food in weight losing older patients with Parkinson's disease.
AB  - AIM: The aim of this paper was to investigate to what extent parkinsonian
      symptoms, including mild dysphagia and other eating problems, could influence the
      choice of consistency and the amount of food intake and if this could be related
      to weight loss as an expression of the underlying neurodegenerative process.
      BACKGROUND: Previous studies show that patients with Parkinson's disease tend to
      lose body weight even early during the disease. DESIGN: The design was a
      longitudinal prospective study. METHODS: Twenty-six free-living Parkinson's
      disease patients and 26 age- and sex-matched controls were investigated twice,
      with one-year apart, with focus on Parkinson's disease symptoms, as well as
      swallowing function. Intake of food items and food consistency were assessed by
      food records, completed over three consecutive days at each investigation.
      RESULTS: In patients with weight loss, motor symptoms, problems with activities
      of daily living and problems with eating, related to motor symptoms, increased
      and they had more dysphagia compared with their controls. They consumed lower
      amounts of fluid and solid food on both investigated occasions, compared with
      their controls. Multiple regression analysis showed that weight loss was
      associated with female gender, eating difficulties related to activities of daily
      living and preference towards soft food, but negatively correlated with age.
      CONCLUSION: Parkinson's disease patients with weight loss seemed to avoid solid
      food, partly because of eating difficulties. Eating problems, as well as weight
      loss, could be because of the underlying disease, even when it is not at an
      advanced stage. RELEVANCE TO CLINICAL PRACTICE: Caring for patients with
      Parkinson's disease should not only include medical treatment, but also support
      for adequate food intake to prevent weight loss.

PMID- 17038102
TI  - People with severe dementia exhibit episodes of lucidity. A population-based
      study.
AB  - AIMS AND OBJECTIVES: To describe frequency and characteristics of people with
      severe dementia who according to care providers, exhibit ELs in a population of
      those with dementia in institutional care. BACKGROUND: There are reports in the
      literature concerning episodes when the resident unexpectedly says or acts in a
      way that surprises the care provider because the resident seems to be much more
      aware of her/his situation than usual. This is labelled 'episodes of lucidity'
      (ELs). DESIGN: The study is based on data from a point prevalence study from
      institutions for the older people in northern Sweden in May 2000. METHODS: Out of
      3804 residents, assessed by key care providers, by means of the Multi-Dimensional
      Dementia Assessment Scale (MDDAS) with questions about ELs added, 92 residents
      were found to have severe dementia and difficulties with verbal communication.
      The key care providers' competence in assessing severe dementia was not
      evaluated. An ethics committee approved the study. RESULTS: Fifty-two residents
      (57%) were assessed as exhibiting ELs. Residents who showed ELs had higher
      orientation scores and expressed more emotions than residents who did not show
      ELs. More residents who exhibited ELs took outdoor walks with their care
      providers exhibited ELs than those who did not (P = 0.001). CONCLUSIONS: Every
      second resident with severe dementia and difficulties with verbal communication
      showed ELs. RELEVANCE FOR CLINICAL PRACTICE: The fact that every second resident
      with severe dementia and difficulties with verbal communication showed ELs and
      that this was noticed especially when care providers took outdoor walks with the
      residents imply that closer contact between care providers and residents with
      severe dementia could change the care providers' expectations and enhance
      communication between the parties.

PMID- 17038103
TI  - Multidisciplinary perceptions of the role of nurses and healthcare assistants in
      rehabilitation of older adults in acute health care.
AB  - AIM: This paper describes the perceptions of nurses, healthcare assistants,
      doctors and therapists of rehabilitation and the role of nurses and healthcare
      assistants on an acute older adults ward in a London teaching hospital.
      BACKGROUND: The role perception, education and training and attitudes towards the
      older adults have been identified as barriers that have an impact upon the
      nurses' role within rehabilitation. However, little is known about the role of
      nurses and healthcare assistants in rehabilitation of older adults in acute
      health care. DESIGN: Action research study. METHOD: Twenty-four semi-structured
      interviews were conducted and audio recorded about healthcare professionals'
      understanding of rehabilitation, the type of skills needed and their perceptions
      of the role of nurses and healthcare assistants in rehabilitation. The interview
      transcripts were analysed using the thematic content analysis. RESULTS: The
      findings suggest that the therapists relied on nurses and healthcare assistants
      for therapy carry-over. Healthcare assistants were perceived as the professional
      group who could deliver therapy carry-over. There was an evidence of role
      hierarchy as healthcare assistants perceived that they were not actively involved
      in decision-making or discharge planning. CONCLUSION: This paper suggests that
      healthcare assistants and nurses are viewed as the professional group best placed
      to deliver therapy carry-over. However, whilst there is an acknowledgement of
      their role, there remains a reluctance to acknowledge healthcare assistants as a
      professional group and to involve them within decision-making and discharge
      planning. RELEVANCE TO CLINICAL PRACTICE: Employers must be seen to advocate,
      support and implement education and training programs for healthcare assistants.
      However, whilst nurses and healthcare assistants have an integral role in
      rehabilitation, there needs to be more research into the how they are supported
      by therapy professionals.

PMID- 17038104
TI  - Nursing home care: whodunit?
AB  - AIMS AND OBJECTIVES: (1) To analyse and compare (changes and differences in)
      activity profiles of various types of nursing home care. (2) To assess the impact
      of integrated care on these activity profiles. BACKGROUND: Because of an ongoing
      introduction of integrated nursing home care, caregivers increasingly have to co
      ordinate their activities, engage into interprofessional relationships and take
      over each other's tasks. Consequently, activity profiles [i.e. combinations of
      (contributions to) care activities and the roles that perform them] are expected
      to change. DESIGN/METHODS: At three measurement points in the period 1999-2003,
      caregivers (in 18 different roles) recorded and listed direct and indirect care
      activities. A total of 41,335 lists were analysed to derive activity profiles of
      traditional, transitional and integrated nursing home care in the Netherlands.
      RESULTS: Traditional, transitional and integrated care shared some comparable
      activity profiles. Integrated care differed from the other types with respect to
      the contribution of the geriatric nurse, recreational activities supervisor,
      nutrition assistant, household assistant and nursing assistant to activities such
      as extra care, handling food and club activities. Contrary to the other roles,
      the licensed practical nurse contributed to (almost) all activities in all types
      of care. CONCLUSIONS: Nursing home care has several recurring activity profiles.
      These profiles are the same in all types of nursing home care. The introduction
      of integrated care implies that particular profiles have to be added to these
      profiles. As a generalist, the licensed practical nurse seems to play a key role
      in all activity profiles. RELEVANCE TO CLINICAL PRACTICE: Because of demographic
      and financial pressures, integrated care for older people becomes increasingly
      important. By addressing the impact of integrated care on activity profiles, this
      paper provides information on how new types of care can be delivered in the most
      effective manner.

PMID- 17038105
TI  - Reality orientation: its use and effectiveness within older person mental health
      care.
AB  - AIM: The aim of this study was to find out how psychiatric nurses use reality
      orientation and perceive its effectiveness in older person mental health care.
      BACKGROUND: The study described in this article relates to how effective reality
      orientation is and how it is used, within older person mental health care. As a
      technique, reality orientation originated in North America in the 1950s. It has
      been defined as an approach which may decrease confusion and dysfunctional
      behaviour patterns in people with dementia. Although there exists some confusion
      as to how reality orientation should be delivered, it is generally agreed that
      reality orientation may be delivered in two ways. Firstly, through constantly
      orientating patients to time, place and person (24-hour reality orientation) and,
      secondly, orientating patients to reality within a group setting. METHODS: Six
      psychiatric nurses practicing in an older person mental health care inpatient
      unit took part in in-depth semi-structured interviews. These six nurses all
      practiced upon the same older person care unit, which was part of a larger
      psychiatric hospital randomly selected from psychiatric hospitals in Dublin,
      Ireland, to take part in the study. The six nurses were also part of a larger
      cohort of nurses who helped the author explore how psychiatric nurses use and
      perceive reality orientation as used in older person and acute inpatient mental
      health care. This was a descriptive qualitative study, using the technique of
      constant comparative analysis as outlined by Strauss and Corbin as a way to code
      interview data and arrange themes that represented what participants had talked
      about in the interviews. More particularly, this form of analysis closely
      resembled the type of open coding as outlined by Strauss and Corbin. The analysis
      of interview data was presented to interview participants prior to the formal
      acceptance of these themes as a valid representation of what interviewees talked
      about. FINDINGS: Upon analysis, interview data yielded five themes. Firstly,
      reality orientation means interacting with patients about the patient's current
      environment and issues in their predicament. Secondly, the sampled nurses use
      reality orientation frequently in their nursing work, with reality orientation
      being most often used in the mornings and evenings. Thirdly, reality orientation
      is implemented through interacting with the patient. It may also be implemented
      as part of other approaches, such as occupational therapy. Fourthly, improvements
      in the areas of orientation and behaviour functioning may be possible through the
      use of reality orientation, although more contemporary research is required to
      validate this. Finally, participants talked of the need for psychiatric nurses
      practicing in older person settings to become more aware of what reality
      orientation entails as an approach, such awareness may be increased through more
      reality orientation-based research. CONCLUSIONS: Interview data point to reality
      orientation being used frequently through nurse-patient interaction. Participants
      talked about how using reality orientation may hold benefits for patients;
      however, on a more cautionary note, participants also raised the need for a
      greater clinical awareness of reality orientation as an approach for use in
      caring for older persons with mental health problems. RELEVANCE TO CLINICAL
      PRACTICE: Psychiatric nurses practicing in older person care environments often
      have to provide care to persons having difficulty comprehending reality. For
      example, a person who is confused through suffering from an organic brain
      disorder such as Alzheimer's disease, or who is expressing a delusion through
      suffering from a functional mental illness such as depression. Taking this into
      consideration, there is an onus on psychiatric nurses to be able to care for
      older persons having difficulties comprehending the reality they are living in.
      Participants in this study identified reality orientation as an approach which
      can be used by psychiatric nurses in attempting to help older persons
      experiencing mental health problems cope with not being able to comprehend and
      recognize their surroundings. Participants also suggested that reality
      orientation may hold some benefits for older disorientated person, such as
      facilitating a greater level of orientation. On a more cautionary note,
      participants talked of the need for psychiatric nurses caring for older persons
      with mental health problems to become more aware of the use of reality
      orientation in clinical practice.

PMID- 17038106
TI  - The experience of caring for someone over 75 years of age: results from a
      Scottish General Practice population.
AB  - AIMS AND OBJECTIVES: To understand the unpaid carers' experiences of looking
      after someone aged over 75 at all stages of their caring career. BACKGROUND: The
      role of, and support for, unpaid carers have become central in the debates
      surrounding community care in the UK. This paper presents the findings of a study
      to elicit the complexities of the caring role and inform the Primary Health Care
      Team to help support carers more effectively. DESIGNS AND METHODS: A quantitative
      research design was employed. Carers of people over 75 years of age in a General
      Practice, who had been previously identified from a screening questionnaire, were
      sent the Carers Assessment of Difficulties Index, the Carers Assessment of
      Satisfactions Index and Carers Assessment of Managing Index questionnaires which
      examine the experience of caring. RESULTS: From a sample of 247 carers, a 70%
      response rate (n = 172) was achieved. Satisfactions lay in the quality of care
      provided; difficulties reflected the potential and actual family tensions
      generated; coping strategies included reframing difficulties, using humour and
      practical problem solving. The data show that caregivers' reactions, such as
      feeling angry about the situation, or the consequences of their involvement, such
      as tensions within the family, cause them more difficulties than the actual care
      giving tasks they perform. CONCLUSION: This study adds to the understanding of
      carers' roles by including carers across a range of situations, including those
      at an early stage of their caring career. Service providers are better able to
      support carers if they understand the complex interplay of difficulties, rewards
      and personal coping strategies associated with the caring role. RELEVANCE TO
      PRACTICE: The study helps illuminate the less obvious, but important, emotional
      aspects of carers' difficulties and suggests strategies which service providers
      may find helpful in assessing carers' needs and determining the appropriate
      interventions.

PMID- 17038107
TI  - Sense of coherence and diabetes-specific stress perceptions of diabetic patients
      in central Mainland China.

PMID- 17038108
TI  - Care plans as the main focus of nursing handover: information exchange model.

PMID- 17038109
TI  - Commentary on Fok MSM & Tsang WYW (2005) Development of an instrument measuring
      Chinese adolescent beliefs and attitudes towards substance abuse. Journal of
      Clinical Nursing 14, 986-994.

PMID- 17038111
TI  - Commentary on Jocham HR, Dassen T, Widdershoven G & Halfens R (2006) Quality of
      life in palliative care cancer patients: a literature review. Journal of Clinical
      Nursing 15, 1188-1195.

PMID- 17038112
TI  - Commentary on Haddad M, Plummer S, Taverner A, Gray R, Lee S, Payne F & Knight D
      (2005) District nurses' involvement and attitudes to mental health problems: a
      three-area cross-sectional study. Journal of Clinical Nursing 14, 976-985.

PMID- 17038113
TI  - Commentary on Sung H-C, Chang S-M & Tsai C-S (2005) Working in long-term care
      settings for older people with dementia: nurses' aides. Journal of Clinical
      Nursing 14, 587-593.

PMID- 17038114
TI  - Commentary on Chung BPM, Wong TKS, Suen ESB & Chung JWY (2005) SARS: caring for
      patients in Hong Kong. Journal of Clinical Nursing 14, 510-517.

PMID- 17038115
TI  - Commentary on Dewing J & Traynor V (2005) Admiral nursing competency project:
      practice development and action research. Journal of Clinical Nursing 14, 695
      703.

PMID- 17038117
TI  - Functional studies of the Ssk1p response regulator protein of Candida albicans as
      determined by phenotypic analysis of receiver domain point mutants.
AB  - The Candida albicans response regulator protein Ssk1p regulates oxidant
      adaptation through the MAPK HOG1 pathway. Deletion mutants lacking SSK1 are
      oxidant sensitive in vitro and are killed more than wild-type (WT) cells by human
      neutrophils. Furthermore, the mutants are avirulent in an invasive murine model,
      and unable to adhere to human esophageal cells. Transcriptional profiling has
      indicated that approximately 25% of all changes occur in genes encoding cell wall
      and stress adaptation functions. In this study, we have investigated the role of
      amino acid residues in the Ssk1p receiver (or regulatory) domain by constructing
      point mutants at positions D556 (putative site of protein phosphorylation) and
      D513 (putative role in divalent metal binding, phosphorylation and conformational
      switching). For each point mutant, their sensitivity to a variety of oxidant
      stress conditions was assessed and correlated with in vitro phosphorylation of
      each Ssk1p receiver domain, phosphorylation of the Hog1p MAP kinase, and
      translocation to the nucleus. We show that a D556N mutant is sensitive to 5 mM
      H(2)O(2) or t-butyl hydroperoxide, similar to a gene knock-out ssk1 mutant, even
      though Hog1p is phosphorylated in the D556N mutant. To resolve this apparent
      paradox, we also demonstrate that Hog1p translocation to the nucleus in the D556N
      mutant is significantly reduced compared with WT cells (CAF2-1). In a second
      point mutant, D513 was changed to a lysine residue (D513K). This mutant had WT
      levels of resistance to peroxide, but in comparison to WT cells and the D556N
      mutant, morphogenesis (yeast to hyphae transition) was inhibited in 10% serum or
      in M-199 medium at 37 degrees C. In the D513K point mutant, constitutive
      phosphorylation of Hog1p was observed, suggesting that a non-conservative change
      (D513K) traps Ssk1p in an active conformation and therefore constitutive Hog1p
      phosphorylation. The inhibition of morphogenesis in D513K is related to a
      downregulation of the transcription factors of morphogenesis, EFG1 and CPH1.
      Another non-conserved point mutant (D556R) was also constructed and
      phenotypically was like the D513K mutant. The receiver domains of the D556N and
      the D513K mutants could not be appreciably phosphorylated in vitro indicating
      that constitutive activation of Hog1p occurs in vivo due to the inability of
      Ssk1p to be phosphorylated at least in the D513K mutant. We speculate that the
      non-conservative changes described above in Ssk1p response regulator may cause
      conformational changes in the Ssk1p that account for phenotype differences
      compared with the D556N mutant that are also Hog-independent.

PMID- 17038118
TI  - A new domain of conjugative relaxase TrwC responsible for efficient oriT-specific
      recombination on minimal target sequences.
AB  - We show that relaxase TrwC promotes recombination between two directly repeated
      oriTs while related relaxases TraI of F and pKM101 do not. Efficient
      recombination required also relaxosome accessory protein TrwA even after deletion
      of TrwA binding sites at oriT, suggesting that the effect of TrwA is mediated by
      protein-protein interactions. TrwC relaxase domain was necessary but not
      sufficient to catalyse recombination efficiently. Full recombinase activity was
      obtained with the N-terminal 600 residues of TrwC. The minimal target sequences
      required for recombination were different at each of the two involved oriTs:
      oriT1 could be reduced to the nic site and TrwC binding site, while oriT2
      required an extended sequence including a set of iterons that are not required
      for conjugation. TrwC-mediated integration of a transferred DNA into a resident
      oriT copy required a complete oriT in the recipient. We observed dramatic changes
      in the efficiency of recombination between tandem oriTs linked to the direction
      of plasmid replication and transcription through oriT1. We propose that
      recombination is triggered by the generation of a single-stranded DNA at oriT1
      that causes TrwC nicking. The resulting TrwC-DNA complex reacts with oriT2,
      excising the intervening DNA. This intermediate can be resolved by host-encoded
      replication functions.

PMID- 17038119
TI  - An alpha-(1,4)-amylase is essential for alpha-(1,3)-glucan production and
      virulence in Histoplasma capsulatum.
AB  - Histoplasma capsulatum is a dimorphic fungus that causes respiratory and systemic
      disease and is capable of surviving and replicating within macrophages. The
      virulence of Histoplasma has been linked to cell wall alpha-(1,3)-glucan;
      however, the role of this polysaccharide during infection, its organization
      within the cell wall, and its synthesis and regulation remain poorly understood.
      To identify genes involved in the biosynthesis of alpha-(1,3)-glucan, we employed
      a forward genetics strategy to isolate physically marked mutants with reduced
      alpha-(1,3)-glucan. Insertional mutants were generated in a virulent strain of H.
      capsulatum by optimization of Agrobacterium tumefaciens-mediated transformation.
      Approximately 90% of these mutants possessed single insertions with no
      chromosomal rearrangements or deletions in the host genome. To confirm the role
      and specificity of identified candidate genes, we phenocopied the disrupted locus
      by either RNA interference or targeted gene deletion. Our findings indicate alpha
      (1,3)-glucan production requires the function of the AMY1 gene product, a novel
      protein with homology to the alpha-amylase family of glycosyl hydrolases, and
      UGP1, a UTP-glucose-1-phosphate uridylyltransferase which synthesizes UDP-glucose
      monomers. Loss of AMY1 function attenuated the ability of Histoplasma to kill
      macrophages and to colonize murine lungs.

PMID- 17038120
TI  - The Vibrio motor proteins, MotX and MotY, are associated with the basal body of
      Na-driven flagella and required for stator formation.
AB  - The four motor proteins PomA, PomB, MotX and MotY, which are believed to be
      stator proteins, are essential for motility by the Na(+)-driven flagella of
      Vibrio alginolyticus. When we purified the flagellar basal bodies, MotX and MotY
      were detected in the basal body, which is the supramolecular complex comprised of
      the rotor and the bushing, but PomA and PomB were not. By antibody labelling,
      MotX and MotY were detected around the LP ring. These results indicate that MotX
      and MotY associate with the basal body. The basal body had a new ring structure
      beneath the LP ring, which was named the T ring. This structure was changed or
      lost in the basal body from a DeltamotX or DeltamotY strain. The T ring probably
      comprises MotX and MotY. In the absence of MotX or MotY, we demonstrated that
      PomA and PomB were not localized to a cell pole. From the above results, we
      suggest that MotX and MotY of the T ring are involved in the incorporation and/or
      stabilization of the PomA/PomB complex in the motor.

PMID- 17038121
TI  - Molecular basis for control of conjugation by bacterial pheromone and inhibitor
      peptides.
AB  - In many bacteria expression of lateral gene transfer and of virulence factors is
      controlled by cell-cell signalling systems. Molecular interactions of microbial
      signal molecules with their cognate receptors are not well understood. For the
      Enterococcus faecalis conjugative plasmid pCF10, the PrgX protein serves as a
      molecular switch controlling expression of conjugation and virulence genes
      encoded by the plasmid. The induction state of a pCF10-carrying donor cell is
      determined by the ratio of two signalling peptides, cCF10 pheromone and iCF10
      inhibitor. Recent analysis of PrgX/cCF10 interactions suggests a mechanism for
      conversion to the induced state. However, the means by which iCF10 peptide
      antagonizes cCF10 activity is unclear, and it has been suggested that inhibitor
      peptides block import of pheromone peptides. We now show that both of these
      peptides interact with the same binding pocket of PrgX, but they differentially
      alter the conformation of the protein and its oligomerization state, resulting in
      opposing biological activities.

PMID- 17038122
TI  - Neisseria gonorrhoeae requires expression of TonB and the putative transporter
      TdfF to replicate within cervical epithelial cells.
AB  - Neisseria gonorrhoeae has evolved a repertoire of iron acquisition systems that
      facilitate essential iron uptake in the human host. Acquisition of iron requires
      both the energy-harnessing cytoplasmic membrane protein, TonB, as well as
      specific outer membrane TonB-dependent transporters (TdTs.) Survival within host
      epithelial cells is important to the pathogenesis of gonococcal disease and may
      contribute to the persistence of infection. However, the mechanisms by which
      gonococci acquire iron within this intracellular niche are not currently
      understood. In this study, we investigated the survival of gonococcal strain
      FA1090 within ME180 human cervical epithelial cells with respect to high affinity
      iron acquisition. Intracellular survival was dependent upon iron supplied by the
      host cell. TonB was expressed in the host cell environment and this protein was
      critical to gonococcal intracellular survival. Furthermore, expression of the
      characterized outer membrane transporters TbpA, FetA and LbpA and putative
      transporters TdfG, TdfH and TdfJ were not necessary for intracellular survival.
      Conversely, intracellular survival was dependent on expression of the putative
      transporter, TdfF. Expression of TdfF was detected in the presence of epithelial
      cell culture media containing fetal bovine serum. Expression was further
      modulated by iron availability. To our knowledge, this study is the first to
      demonstrate the specific requirement for a single iron transporter in the
      survival of a bacterial pathogen within host epithelial cells.

PMID- 17038123
TI  - Structure-based mutagenesis of SigE verifies the importance of hydrophobic and
      electrostatic residues in type III chaperone function.
AB  - Despite sharing little sequence identity, most type III chaperones display a
      similar homodimeric structure characterized by negative charges distributed
      broadly over their entire surface, interspersed with hydrophobic patches. Here we
      have used SigE from Salmonella as a model for class IA type III chaperones to
      investigate the role of these surface-exposed residues in chaperone function.
      SigE is essential for the stability, secretion and translocation of its cognate
      effector, SopB (SigD). We analysed the effect of mutating nine conserved
      hydrophobic and electronegative surface-exposed amino acids of SigE on SopB
      binding, stability, secretion and translocation. Six of these mutations affected
      some aspect of SigE function (Leu14, Asp20, Leu22, Leu23, Ile25 and Asp51) and
      three were without effect (Leu54, Glu92 and Glu99). Our results highlight that
      both hydrophobic and electronegative surfaces are required for the function of
      SigE and provide an important basis for the prediction of side-chain requirements
      for other chaperone-effector pairs.

PMID- 17038124
TI  - A novel ligand bound ABC transporter, LolCDE, provides insights into the
      molecular mechanisms underlying membrane detachment of bacterial lipoproteins.
AB  - The LolCDE complex of Escherichia coli belongs to the ABC transporter superfamily
      and initiates the lipoprotein sorting to the outer membrane by catalysing their
      release from the inner membrane. LolC and/or LolE, membrane subunits, recognize
      lipoproteins anchored to the outer surface of the inner membrane, while LolD
      hydrolyses ATP on its inner surface. We report here that ligand-bound LolCDE can
      be purified from the inner membrane in the absence of ATP. Liganded LolCDE
      represents an intermediate of the release reaction and exhibits higher affinity
      for ATP than the unliganded form. ATP binding to LolD weakens the interaction
      between LolCDE and lipoproteins and causes their dissociation in a detergent
      solution, while lipoprotein release from membranes requires ATP hydrolysis.
      Liganded LolCDE thus reveals molecular events brought about through ATP binding
      and hydrolysis. LolCDE is the first example of an ABC transporter purified with
      tightly bound native substrates. A single molecule of lipoprotein is found to
      bind per molecule of the LolCDE complex.

PMID- 17038125
TI  - Obesity in South Africa.
AB  - South Africa has not been spared in the rampant global increase in obesity.
      Throughout Africa, as elsewhere, ethnicity has a major impact on the incidence
      and pathogenesis of comorbid diseases, particularly diabetes. Combined figures
      for obesity and overweight (body mass index [BMI] > 25 kg m(-2)) obtained across
      all ethnic groups in the adult population in 1998, were 57% for women and 29% for
      men. From the 1960s until the late 1980s, the notion of 'healthy' or 'benign'
      obesity was propagated in South Africa. Not surprisingly, this led to ignorance
      around the problem of obesity, and treatment of some of the comorbid diseases was
      neglected. Fortunately, as an increasing number of seminal studies draw us closer
      to reality, the misperception of benign obesity is being corrected. This is
      allowing us to address the real issues underlying the current epidemic, and to
      recognize and manage the comorbid diseases, in particular type 2 diabetes. A new
      framework for research is also emerging as we begin to define the factors
      underlying the impact of ethnicity on obesity.

PMID- 17038126
TI  - The management of osteoarthritis in the obese patient: practical considerations
      and guidelines for therapy.
AB  - Obesity and osteoarthritis (OA) co-exist in an increasing part of the population.
      The two diseases intertwine in several ways. The evolution in the population
      shows a tendency towards deterioration of both by increasing general age and
      weight. The two diseases share pathogenetic features and the development of one
      disease increases the risk of the other and may be the onset of a vicious circle.
      There is a link between treatments of these two diseases as well. There is now
      solid (gold) evidence that by treating effectively the obesity of patients with
      co-occurring OA, the functional status is dramatically ameliorated; the short
      term results are equal to that of a joint replacement. The long-term efficacy of
      a weight loss remains to be shown. OA is definitely one of many diseases in which
      obesity must be taken seriously into account when planning a correct treatment of
      patients. The regimens used in the controlled studies of such patients are
      reviewed and it may be concluded that practical aspects of the dietary
      intervention in obese patients with OA are not different from general
      recommendations.

PMID- 17038127
TI  - Obesity and prognosis of breast cancer.
AB  - Obesity has a complicated relationship to both breast cancer risk and the
      clinical behaviour of the established disease. It is suggested that obesity is
      associated with both an increased risk of developing breast cancer risk and worse
      prognosis after disease onset. In post-menopausal women, various measures of
      obesity such as body mass index, weight, weight gain and waist : hip ratio have
      all been positively associated with risk of developing breast cancer. In most but
      not all case-control and prospective cohort studies, an inverse relationship has
      been found between weight and breast cancer among pre-menopausal women. Some data
      suggest that adult weight gain and central obesity increase the risk of pre
      menopausal breast cancer. Obesity at the time of diagnosis is thought to be
      significant as a poor prognostic factor. Obesity is associated with adverse
      outcomes in both pre- and post-menopausal women with breast cancer. Many cancer
      survivors seek ways to minimize the risk of recurrence and death because of
      breast cancer. Despite complex and at times controversial data, enough evidence
      is available at present to suggest that weight management should be a part of the
      strategy to prevent the occurrence, recurrence and death because of breast
      cancer. In this review the effect of obesity on the prognosis of breast cancer is
      examined in detail.

PMID- 17038128
TI  - Obesity and disability - a short review.
AB  - The prevalence of both obesity and disability is increasing globally and there is
      now growing evidence to suggest that these two health priorities may be linked.
      This paper explores the evidence linking obesity to muscular-skeletal conditions,
      mental health disorders and learning disabilities in both adult and child
      populations. The impact of obesity on the four most prevalent disabling
      conditions in the UK (arthritis, mental health disorders, learning disabilities
      and back ailments) has been examined through novel data analysis of the 2001
      Health Survey for England and UK Back Exercise And Manipulation trial data.
      Together these analyses strongly suggest that whether the cause or result of
      disability, obesity is undeniably implicated, thus presenting a serious public
      health priority. Future research efforts are required to strengthen the evidence
      base examining obesity in back disorders, mental health and learning
      disabilities, in order to improve current clinical management.

PMID- 17038129
TI  - An overview of obesity-specific quality of life questionnaires.
AB  - The measurement of quality of life in patients with obesity is useful to evaluate
      the effects of treatment (including bariatric surgery) and may influence the
      development of clinical pathways, service provision, healthcare expenditures and
      public health policy. Consequently, clinicians, researchers and policy makers
      must rely on valid measurement instruments. We reviewed 11 obesity-specific
      quality of life questionnaires and classified them according to their domain of
      interest and described their measurement properties (specifications, validity,
      reliability, responsiveness and interpretability). We found that (i) nine
      questionnaires were developed specifically to be used as evaluative instruments
      in clinical trials; (ii) only three targeted populations with morbid obesity
      (body mass index > 40 kg m(-2)); (iii) construct validity was properly studied in
      three questionnaires; (iv) demonstration of responsiveness from independent
      randomized controlled trials was available for two of the 11 questionnaires; (v)
      keys to interpretation of scores were provided for three questionnaires. Future
      research should include further validation and a better definition of the
      interpretability of existing instruments.

PMID- 17038130
TI  - How much may I eat? Calorie estimates based upon energy expenditure prediction
      equations.
AB  - How much may I eat? Most healthcare workers, when asked this question, have
      insufficient knowledge to educate their patients on a healthy energy intake
      level. In this review we examine the available methods for estimating adult
      energy requirements with a focus on the newly developed National Academy of
      Sciences/Institute of Medicine (NAS/IOM) doubly-labelled water total energy
      expenditure (TEE) prediction equations. An overview is first provided of the
      traditional factorial method of estimating energy requirements. We then extend
      this overview by exploring the development of the NAS/IOM TEE prediction models
      and their role in estimating energy requirements as a function of sex, age,
      weight, height and physical activity level. The NAS/IOM prediction models were
      developed for evaluating group energy requirements, although the formulas can be
      applied in individual 'example' patients for educational purposes. Potential
      limitations and interpretation issues of both the factorial and NAS/IOM methods
      are examined. This information should provide healthcare professionals with the
      tools and understanding to appropriately answer the question, 'How much may I
      eat?'

PMID- 17038131
TI  - Carl von Linne (1707-1778).

PMID- 17038133
TI  - Pacemaker diagnosis of sleep disordered breathing.

PMID- 17038134
TI  - Feasibility of automated detection of advanced sleep disordered breathing
      utilizing an implantable pacemaker ventilation sensor.
AB  - OBJECTIVES: This study tested the feasibility of automatically detecting advanced
      sleep disordered breathing (SDB) from a pacemaker trans-thoracic impedance
      sensor. BACKGROUND: SDB is prevalent yet under-diagnosed in patients with
      cardiovascular disease. The potential for automated detection of SDB in patients
      receiving pacemakers with respiration sensors has not been fully explored. We
      hypothesized that the trans-thoracic impedance sensor could be utilized for
      automatic detection of advanced SDB. METHODS: Patients underwent overnight
      polysomnography (PSG). The pacemaker trans-thoracic impedance signal was
      simultaneously recorded and time synchronized with the polysomnograph.
      Cardiovascular health variables were abstracted from medical records. Apnea was
      defined as cessation of inspiratory airflow lasting 10 seconds or longer.
      Hypopnea was defined as a reduction of tidal volume of at least 30% from baseline
      tidal volume, lasting 10 seconds or more. A computer algorithm (PM-A) was
      developed to automatically detect SDB from the pacemaker impedance sensor data.
      The performance of automated SDB detection was compared against PSG. RESULTS:
      Sixty patients (aged 69 +/- 12 years, 45 males) were studied. Advanced SDB
      (moderate or severe) was diagnosed in 40 patients. Severe SDB (apnea-hypopnea
      index [AHI]> or = 30) was diagnosed in 32 patients (53%), but only 5 patients had
      prior diagnosis of the disease. Moderate SDB (30 > AHI > 15) was diagnosed in 8
      patients of whom only two were previously diagnosed. Cardiovascular health
      variables did not predict the presence of advanced SDB. PM-A derived AHI
      correlated with that of the PSG (r = 0.80, P < 0.01). The algorithm identified
      patients with advanced SDB with 82% sensitivity and 88% specificity. CONCLUSIONS:
      It is feasible to automatically measure SDB severity using a pacemaker trans
      thoracic impedance sensor. Advanced SDB was frequently undiagnosed in this cohort
      of pacemaker patients.

PMID- 17038135
TI  - Pacemaker longevity: are we getting what we are promised?
AB  - BACKGROUND: Although pacemaker manufacturers provide projections on longevity,
      these projections cannot be relied upon due to the assumptions of output
      parameters being far in excess of those programmed in clinical practice.
      OBJECTIVE: The purpose of this review was to compare the actual longevity to the
      calculated longevity of pacemakers based on battery cell characteristics taking
      into account individual programmed parameters, mode, degree of usage, and percent
      pacing. This was also compared to the manufacturers' own projected longevities.
      METHODS: Patients who had a pacemaker replaced between 1998 and 2003 were
      included (n = 124). Cell characteristics were obtained from manufacturers and
      programmed parameters were obtained at each visit. Stepwise calculations were
      done for each visit to find current drain during each interval, and then were
      used in a weighted average to find the total average lifetime current drain. This
      was subsequently used to find a calculated longevity for each pacemaker to be
      compared to the actual longevity observed. RESULTS: The pacemakers lasted 491+/
      92 days (mean+/-SEM) less than calculated. There was also a difference between
      dual- and single-chamber devices (though not statistically significant).
      Moreover, it was found that there were significant differences between
      manufacturers. CONCLUSIONS: There appears to be a significant discrepancy between
      calculated and actual longevities, confirming that battery depletion occurs
      earlier than expected. This suggests that current drain expended for ancillary
      functions may be considerable. Another factor may be pre-implantation drain.
      Vigilance with programming of outputs, modes, sensors, heart rates, and ancillary
      functions could potentially extend longevity and postpone/obviate the need for
      costly repeat surgery with its attended risk of complications. Furthermore, the
      differences between manufacturers seem to parallel the clinical impressions.

PMID- 17038136
TI  - Right ventricular outflow tract pacing: practical and beneficial. A 9-year
      experience of 460 consecutive implants.
AB  - BACKGROUND: Pacing from the right ventricular apex (RVA) in patients with
      ventricular dysfunction has been identified as a possible contributor to
      deterioration of ventricular function. Therefore, alternative pacing sites such
      as the right ventricular outflow tract (RVOT) are receiving intensified scrutiny.
      An unresolved question is whether technical, procedural, and stability issues are
      comparable for the RVA and the RVOT. METHODS: This report details 460 consecutive
      ventricular pacing lead implants with the primary intended site in the RVOT.
      Patients were evaluated for success, complication rates, and followed-up for
      stability of pacing parameters. The total patient implant population included 300
      male and 170 female patients with a mean age of 70.6 years. Ten patients were
      excluded from the analysis, since there was a primary indication and intention to
      implant in the RVA, leaving a total of 460 patients for analysis. The indications
      for pacing were symptomatic bradycardia due to any cause and/or Mobitz II or
      complete heart block. There was no clinical evidence of heart failure in 420
      patients. In 40 patients with heart failure, the indication for pacing was
      cardiac resynchronization therapy using the RVOT as an alternate site when pacing
      from a branch vein of the coronary sinus was not possible. Outcome information
      was obtained from the implanter's clinic. RESULTS: The overall success rate in
      the RVOT was 84% over the total 9-year period with a 92% success rate in the last
      4(1/2) years, using the RVOT technique described. At 20 months in a subgroup
      comparison of RVOT and RVA implants, there was no significant difference in
      pacing threshold, R-wave sensing, or pacing lead impedance. Dislodgment occurred
      in only 1 of 460 patients. Reasons for failure to implant in the RVOT include
      inability to find a stable position with adequate pacing and sensing thresholds
      (related to anatomy, scarred myocardium, pulmonary hypertension, tricuspid
      regurgitation), hemodynamic instability limiting time for implant, and a learning
      curve. Long-term stability and lead performance were excellent, and certain acute
      and chronic complications of RV pacing did not occur.

PMID- 17038137
TI  - Right ventricular outflow tract pacing: radiographic and electrocardiographic
      correlates of lead position.
AB  - OBJECTIVE: To characterize the pacing site in an unselected series of patients
      undergoing right ventricular outflow tract (RVOT) lead placement and investigate
      the role of the electrocardiogram (ECG) in predicting implantation. BACKGROUND:
      Right ventricular apical pacing is associated with long-term adverse effects on
      left ventricular function, fuelling interest in alternative pacing sites,
      especially the RVOT. Previous studies have been conflicting, possibly due to poor
      definition of pacing site within the RVOT. METHODS: In 150 patients undergoing
      pacemaker implantation, implanters were asked to place the lead in the RVOT.
      Radiographs were performed in the antero-posterior (AP) and 40 degrees right and
      left anterior-oblique projections post procedure. Fifty-six had left lateral
      radiographs. Lead position was categorized using AP/RAO (right anterior oblique)
      to confirm RVOT placement and left anterior oblique to distinguish free wall from
      septum. A 12-lead ECG was performed during ventricular pacing. RESULTS: Leads
      were below the RVOT in 18. Of the remaining 132, the majority (94%) were in the
      inferior/low RVOT. Eighty-one out of 132 were septal and 51 free wall. Septal
      sites were associated with shorter QRS duration (134 ms vs 143 ms, P < 0.02).
      Free wall sites displayed more frequent notching of the inferior leads (P <
      0.01). A negative deflection in lead I provided a positive predictive value of
      90% for septal sites. In those with lateral radiographs, a posteriorly projected
      lead was 100% specific for septal placement. CONCLUSIONS: This study demonstrates
      the heterogeneity of lead placement within the RVOT. Septal and free wall sites
      display characteristic ECG patterns which may be used to aid placement. The left
      lateral radiograph is useful in confirming a true septal location.

PMID- 17038138
TI  - Does RV lead positioning provide additional benefit to cardiac resynchronization
      therapy in patients with advanced heart failure?
AB  - BACKGROUND AND OBJECTIVES: The left ventricular (LV) stimulation site is
      currently recommended to position the lead at the lateral wall. However, little
      is known as to whether right ventricular (RV) lead positioning is also important
      for cardiac resynchronization therapy. This study compared the acute hemodynamic
      response to biventricular pacing (BiV) at two different RV stimulation sites: RV
      high septum (RVHS) and RV apex (RVA). METHODS AND RESULTS: Using micro-manometer
      tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS)
      and LV free wall in 33 patients. Changes in LV dP/dt(max) and dP/dt(min) from
      baseline were compared between RVA and RVHS. BiV pacing increased dP/dt(max) by
      30.3 +/- 1.2% in RVHS and by 33.3 +/- 1.7% in RVA (P = n.s.), and decreased
      dP/dt(min) by 11.4 +/- 0.7% in RVHS and by 13.0 +/- 1.0% in RVA (P = n.s.). To
      explore the optimal combination of RV and LV stimulation sites, we assessed
      separately the role of RV positioning with LV pacing at anterolateral (AL),
      lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or
      LAT, the increase in dP/dt(max) with RVHS pacing was smaller than that with RVA
      pacing (AL: 12.2 +/- 2.2% vs 19.3 +/- 2.1%, P < 0.05; LAT: 22.0 +/- 2.7% vs 28.5
      +/- 2.2%, P < 0.05). There was no difference in dP/dt(min) between RVHS- and RVA
      pacing in individual LV segments. CONCLUSIONS: RVHS stimulation has no overall
      advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was
      equivalent with RVA in combination with the PL LV site, while RVA was superior to
      RVHS in combination with AL or LAT LV site.

PMID- 17038139
TI  - Effect of percutaneous interventions within the coronary sinus on the success
      rate of the implantations of resynchronization pacemakers.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) becomes a "gold standard" in
      therapy of selected patients with advanced heart failure. We set out to evaluate
      the feasibility and safety of percutaneous interventions within coronary sinus
      (CS) and their effect on the success rate of left ventricular (LV) lead
      implantation during CRT. METHODS: The study analyzed eight consecutive patients
      with the indications for CRT, who needed additional procedures within CS to
      overcome technical problems during left ventricular (LV) electrode implantation.
      The analyzed group consisted of three subgroups: patients in whom percutaneous
      balloon angioplasty within CS was needed (n = 4); patients with acute instability
      of the lead, requiring stenting of the vein to fix the electrode (n = 2); and
      patients with the stenting of CS due to late dislocation of the lead (n = 2).
      Success rate, procedure duration, fluoroscopy, complications, and electrical
      parameters of leads were analyzed. RESULTS: Success rate of the procedures was
      87.5%; additional interventions increased overall efficacy of CRT implantation at
      our center from 88% to 98% (P < 0.05). Procedure duration (155.0 minute) and
      fluoroscopy time (42.5 minute) remained acceptable for the patient and operator;
      however, both were higher than in the procedures performed routinely in our
      hospital. Electrical properties of the LV leads were stable and within normal
      ranges during the observation period. We noted two local dissections of CS during
      the procedure, which remained clinically silent. CONCLUSION: Percutaneous
      interventions within CS seem to be feasible and safe treatment options, which can
      improve the short- and long-term success rates of CRT.

PMID- 17038140
TI  - Atrioventricular junction ablation followed by resynchronization therapy in
      patients with congestive heart failure and atrial fibrillation (AVERT-AF) study
      design.
AB  - Atrial fibrillation (AF) and congestive heart failure (CHF) affect millions of
      patients in the United States. Several studies suggest that AF and in particular
      the irregular ventricular response might be contributing to the left ventricular
      dysfunction. Studies that compared pharmacologic rate control to atrioventricular
      junction (AVJ) ablation followed by right ventricular pacing which restores a
      regular ventricular response, failed to show an improvement when compared to
      pharmacological rare control. These results might be explained by the fact that
      while AVJ ablation restored a regular ventricular response, it subjected patients
      to the detrimental effects of RV apical pacing. The AVERT-AF trial (Atrio
      VEntricular Junction Ablation Followed by Resynchronization Therapy in patients
      with CHF and AF) is a prospective, randomized, double-blinded, multicenter trial
      that will be testing the hypothesis that AVJ ablation followed by biventricular
      pacing significantly improves exercise capacity and functional status compared to
      pharmacologic rate control in patients with chronic AF and depressed ejection
      fraction, regardless of rate or QRS duration. A total of 180 patients will be
      enrolled to test the primary endpoint, which is exercise duration.
      Patients_enrollment will begin in summer 2006 and is expected to be completed in
      2008. The results of this trial should help define the best treatment option for
      this common arrhythmia in patients with left ventricular dysfunction.

PMID- 17038141
TI  - Signal-averaged P wave reflects change in atrial electrophysiological substrate
      afforded by verapamil following cardioversion from atrial fibrillation.
AB  - BACKGROUND: Detailed analysis of signal-averaged P waves (SAPW) can provide
      insights into atrial electrophysiology. Abbreviated dosing of verapamil prior to
      cardioversion improves outcome at 1 week postcardioversion. The mechanism by
      which verapamil manifests benefit is uncertain. We hypothesized the SAPW would
      reflect any change in atrial electrophysiologic substrate afforded by verapamil
      when compared with controls. METHODS: We investigated 23 patients attending
      external cardioversion of persistent atrial fibrillation (AF) (6 female; mean age
      68 years). Patients were randomized to verapamil 240 mg daily in three divided
      doses 3 days before cardioversion and 1 week after, or usual medication. SAPW
      recordings were performed during sinus rhythm (SR) immediately after
      cardioversion, at 24 hours and 1 week. RESULTS: The groups were comparable in
      terms of age, gender, left atrial size, and duration of AF. Eight of nine
      patients prescribed verapamil maintained SR at 1 week postcardioversion compared
      with 6 of 14 controls (P = 0.027). SAPW spectral analysis delivered higher energy
      for patients prescribed verapamil (median (IQ range)); 40.8 (33.4-95.1) versus
      25.7 (19.0-38.0) for energy within 20-150 Hz, P20 (microV(2)x s; P = 0.03). There
      was no difference in P-wave duration (PWD) or root mean square of the terminal 30
      ms between the two groups. Early reinitiation occurred in patients with
      significantly lower P-wave energy 19.6 (12.9-24.6) versus 39.9 (24.0-47.0) (P =
      0.017). CONCLUSIONS: Verapamil 240 mg daily for 3 days prior to cardioversion and
      1 week after reduces early recurrence of AF. The SAPW observations indicate
      change in atrial electrophysiologic substrate might be responsible for benefit
      afforded by verapamil.

PMID- 17038142
TI  - Decremental ramp atrial extrastimuli pacing protocol for the induction of
      atrioventricular nodal re-entrant tachycardia and other supraventricular
      tachycardias.
AB  - AIM: The primary aim of this study was to evaluate the utility of decremental
      ramp atrial extrastimuli pacing protocol (PRTCL) for induction of
      atrioventricular nodal re-entrant tachycardia (AVNRT), and other supraventricular
      tachycardias (SVTs), compared to standard (STD) methods. METHODS: The study
      cohort of 121 patients (age 57.51 +/- 14.02 years) who presented with documented
      SVTs and/or symptoms of palpitations and dizziness, and underwent invasive
      electrophysiological evaluation was divided into Group I (AVNRT, n = 42) and
      Group II (Control, n = 79). The PRTCL involved a train of six atrial
      extrastimuli, delivered in a decremental ramp fashion. The STD methods included
      continuous burst and rapid incremental pacing up to atrioventricular (AV) block
      cycle length, and single and occasionally double atrial extrastimuli.
      Prolongation in the Atrio-Hisian (Delta-AH) intervals achieved by both methods
      were compared, as were induction frequencies. RESULTS: In Group I, three
      categories of responses--(1) induction of AVNRT, (2) induction of echo beats
      only, and (3) none--were observed in 29 (69%), 11 (26%), and 2 (5%) patients with
      the PRTCL, when compared with 14 (33%), 16 (38%), and 12 (29%) patients with STD
      methods in the baseline state without the use of pharmacological agents. The
      Delta-AH intervals for each of these three categories were larger using PRTCL
      versus STD methods; 293.3 +/- 95.2 ms versus 192.9 +/- 61.4 ms (P < 0.005), 308.6
      +/- 68.5 ms versus 189. 9 +/- 64.9 ms (P < 0.0005), and 203.0 +/- 86.3 ms versus
      145.8 +/- 58.9 ms (P = NS), respectively. In Group II, in one patient with dual
      AV nodal physiology but no clinical tachycardia, the PRTCL induced nonsustained
      (12 beats) AVNRT. Additionally, in this group, both PRTCL and STD methods induced
      atrial tachycardia in two patients and orthodromic AV re-entrant tachycardia in
      one patient. CONCLUSION: Decremental ramp atrial extrastimuli pacing PRTCL
      demonstrates a superior response for induction of typical AVNRT as compared to
      STD techniques. Because of easy and reliable induction of AVNRT and echo beats by
      the PRTCL, we recommend it as a method to increase the likelihood of induction of
      AVNRT. For induction of other SVTs, the PRTCL and the STD methods are comparable.

PMID- 17038143
TI  - The electrophysiological characteristics in patients with ventricular stimulation
      inducible fast-slow form atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) can usually be
      induced by atrial stimulation. However, it seldom may be induced with only
      ventricular stimulation, especially the fast-slow form of AVNRT. The purpose of
      this retrospective study was to investigate the specific electrophysiological
      characteristics in patients with the fast-slow form of AVNRT that could be
      induced with only ventricular stimulation. METHODS: The total population
      consisted of 1,497 patients associated with AVNRT, and 106 (8.4%) of them had the
      fast-slow form of AVNRT and 1,373 (91.7%) the slow-fast form of AVNRT. In
      patients with the fast-slow form of AVNRT, the AVNRT could be induced with only
      ventricular stimulation in 16 patients, Group 1; with only atrial stimulation or
      both atrial and ventricular stimulation in 90 patients, Group 2; and with only
      atrial stimulation in 13 patients, Group 3. We also divided these patients with
      slow-fast form AVNRT (n = 1,373) into two groups: those that could be induced
      only by ventricular stimulation (Group 4; n = 45, 3%) and those that could be
      induced by atrial stimulation only or by both atrial and ventricular stimulation
      (n = 1.328, 97%). RESULTS: Patients with the fast-slow form of AVNRT that could
      be induced with only ventricular stimulation had a lower incidence of an
      antegrade dual AVN physiology (0% vs 71.1% and 92%, P < 0.001), a lower incidence
      of multiple form AVNRT (31% vs 69% and 85%, P = 0.009), and a more significant
      retrograde functional refractory period (FRP) difference (99 +/- 102 vs 30 +/- 57
      ms, P < 0.001) than those that could be induced with only atrial stimulation or
      both atrial and ventricular stimulation. The occurrence of tachycardia stimulated
      with only ventricular stimulation was more frequently demonstrated in patients
      with the fast-slow form of AVNRT than in those with the slow-fast form of AVNRT
      (15% vs 3%, P < 0.001). Patients with the fast-slow form of AVNRT that could be
      induced with only ventricular stimulation had a higher incidence of retrograde
      dual AVN physiology (75% vs 4%, P < 0.001), a longer pacing cycle length of
      retrograde 1:1 fast and slow pathway conduction (475 +/- 63 ms vs 366 +/- 64 ms,
      P < 0.001; 449 +/- 138 ms vs 370 +/- 85 ms, P = 0.009), a longer retrograde
      effective refractory period of the fast pathway (360 +/- 124 ms vs 285 +/- 62 ms,
      P = 0.003), and a longer retrograde FRP of the fast and slow pathway (428 +/- 85
      ms vs 362 +/- 47 ms, P < 0.001 and 522 +/- 106 vs 456 +/- 97 ms, P = 0.026) than
      those with the slow-fast form of AVNRT that could be induced with only
      ventricular stimulation. CONCLUSION: This study demonstrated that patients with
      the fast-slow form of AVNRT that could be induced with only ventricular
      stimulation had a different incidence of the antegrade and retrograde dual AVN
      physiology and the specific electrophysiological characteristics. The mechanism
      of the AVNRT stimulated only with ventricular stimulation was supposed to be
      different in patients with the slow-fast and fast-slow forms of AVNRT.

PMID- 17038144
TI  - Spatial distribution of repolarization and depolarization abnormalities evaluated
      by body surface potential mapping in patients with Brugada syndrome.
AB  - BACKGROUND: Mutations in sodium channel gene, SCN5A, have been identified in
      Brugada syndrome, but it is still unclear as to how sodium channel dysfunction
      relates to arrhythmogenesis. We examined spatial distribution of both
      repolarization and depolarization abnormalities in patients with Brugada syndrome
      by using 87-leads body surface potential mapping (BSPM). METHODS: BSPM was
      recorded under baseline condition and after pharmacological interventions in 28
      patients with Brugada syndrome (27 males, 49 +/- 14 years). The ST-segment
      amplitude 20 ms after the end of QRS (ST20), QRS duration, and corrected recovery
      time (RTc) were measured in all 87-leads, and averaged among 6-leads (D-F, 5-6)
      reflecting right ventricular outflow tract (RVOT) potentials and the other 81
      leads. RESULTS: The ST20 was elevated at baseline, normalized by isoproterenol,
      and augmented by pilsicainide in only the RVOT. The RTc was longer at baseline
      and increased by pilsicainide in only the RVOT. On the other hand, the QRS
      duration was slightly widened at baseline, further increased by pilsicainide, but
      not changed by isoproterenol in both leads. CONCLUSIONS: The ST-segment elevation
      and the RTc prolongation were localized and modulated by agents only in the RVOT
      region, while the slight QRS widening at baseline and further increase by
      pilsicainide were observed homogeneously. Our data suggest that depolarization
      abnormalities are distributed homogeneously, whereas repolarization abnormalities
      are localized in the RVOT.

PMID- 17038145
TI  - Ventricular repolarization and heart rate responses during cardiovascular
      autonomic function testing in LQT1 subtype of long QT syndrome.
AB  - BACKGROUND: In the most prevalent LQT1 form of inherited long QT syndrome
      symptoms often occur during abrupt physical or emotional stress. Sympathetic
      stimulation aggravates repolarization abnormalities in experimental LQT1 models.
      We hypothesized that autonomic function tests might reveal the abnormal
      repolarization in asymptomatic LQT1 patients. METHODS: We measured heart rates
      (HRs) and QT intervals in nine asymptomatic carriers of a C-terminal KCNQ1
      mutation and 8 unaffected healthy subjects using an approach of global QT values
      derived from 28 simultaneous electrocardiographic leads on beat-to-beat base
      during Valsalva maneuver, mental stress, sustained handgrip, and light supine
      exercise. RESULTS: LQT1 patients exhibited impaired shortening of both QTpeak and
      QTend intervals during autonomic interventions but exaggerated lengthening of the
      intervals--a QT overshoot--during the recovery phases. The number of tests with a
      QT overshoot was 2.4 +/- 1.7 in LQT1 patients and 0.8 +/- 0.7 in unaffected
      subjects (P = 0.02). Valsalva strain prolonged T wave peak to T wave end interval
      (TPE) in LQT1 but not in unaffected patients. LQT1 patients showed diminished HR
      acceleration in response to adrenergic challenge whereas HR responses to vagal
      stimuli were similar in both groups. CONCLUSIONS: Standard cardiovascular
      autonomic provocations induce a QT interval overshoot during recovery in
      asymptomatic KCNQ1 mutation carriers. Valsalva maneuver causes an exaggerated
      fluctuation of QT and TPE intervals partly explaining the occurrence of cardiac
      events during abrupt bursts of autonomic activity in LQT1 patients.

PMID- 17038147
TI  - Syncope in adults: terminology, classification, and diagnostic strategy.
AB  - Syncope is a relatively common clinical syndrome that is a subset of a broader
      range of conditions that cause transient loss of consciousness (TLOC). Other TLOC
      conditions include seizures, concussions, and intoxications. However, despite
      frequent confusion in the medical literature, syncope is and should be clearly
      distinguished from those other causes of TLOC by virtue of its pathophysiology;
      specifically, syncope is the result of self-terminating inadequacy of global
      cerebral nutrient perfusion, while the other forms of TLOC have different
      etiologies. Unfortunately, the diagnostic evaluation of syncope remains for the
      most part poorly managed and inefficient. Careful history-taking, physical
      examination, and judicious use of tests can not only increase the diagnostic
      yield of the evaluation, but also increase patient safety and reduced overall
      healthcare costs.

PMID- 17038148
TI  - Acute subclavian or axillary vein occlusion during biventricular pacemaker
      implantation.
AB  - During biventricular pacemaker implantation, multiple punctures of the subclavian
      vein were performed and venous occlusion was apparent during the procedure, which
      in one case was stopped before lead insertion and in the other patient new access
      has to be forced through the occlusion by removing one of the already implanted
      leads. For implanting physicians, it is important to know that acute venous
      occlusion may occur during lead implantation.

PMID- 17038149
TI  - Lead interaction: rare cause of oversensing during implantation procedure of
      implantable cardioverter-defibrillator system.
AB  - A variety of etiologies can cause erroneous detection in patients with
      implantable cardioverter defibrillator (ICDs). Interaction between two
      endocardial leads is rare and uncommon in causing electrical noise. During a
      reimplantation procedure of an ICD system in a 68-year-old man, additional
      electrical signals could be detected. The interaction between two endocardial
      defibrillation leads was identified as the cause of sensing problems. When it is
      not possible to extract the nonfunctional endocardial lead during implantation of
      the new electrode, it should be implanted away and not in parallel from the old
      one to avoid interaction between them. A variety of etiologies can cause
      erroneous detection in patiens with ICD. Interaction between two endocardial
      leads is rare and uncommon to cause electrical noise.

PMID- 17038150
TI  - Inadequate ICD discharges due to diaphragmatic electromyopotential oversensing as
      the first sign of right ventricular lead perforation.
AB  - Right ventricular lead perforation, when acute, is a rare but potentially life
      threatening complication of implantable cardioverter defibrillator (ICD) therapy.
      We report about a patient with early lead perforation presenting with repetitive
      ICD discharges due to oversensing of diaphragmatic electromyopotentials and
      describe the management of this complication.

PMID- 17038146
TI  - Brugada syndrome.
AB  - First introduced as a new clinical entity in 1992, the Brugada syndrome is
      associated with a relatively high risk of sudden death in young adults, and
      occasionally in children and infants. Recent years have witnessed a striking
      proliferation of papers dealing with the clinical and basic aspects of the
      disease. Characterized by a coved-type ST-segment elevation in the right
      precordial leads of the electrocardiogram (ECG), the Brugada syndrome has a
      genetic basis that thus far has been linked only to mutations in SCN5A, the gene
      that encodes the alpha-subunit of the sodium channel. The Brugada ECG is often
      concealed, but can be unmasked or modulated by a number of drugs and
      pathophysiological states including sodium channel blockers, a febrile state,
      vagotonic agents, tricyclic antidepressants, as well as cocaine and propranolol
      intoxication. Average age at the time of initial diagnosis or sudden death is 40
      +/- 22, with the youngest patient diagnosed at 2 days of age and the oldest at 84
      years. This review provides an overview of the clinical, genetic, molecular, and
      cellular aspects of the Brugada syndrome, incorporating the results of two recent
      consensus conferences. Controversies with regard to risk stratification and newly
      proposed pharmacologic strategies are discussed.

PMID- 17038151
TI  - Isolated giant cell myocarditis in the atrium: an incidental finding?
AB  - Giant cell myocarditis (GCM) is an uncommon disorder that affects ventricular
      myocardium causing severe left ventricular dysfunction and ventricular
      arrhythmias. We report a case of GCM that only affected the atrium sparing the
      ventricle.

PMID- 17038152
TI  - Atrio-ventricular synchronization by single VDD lead inserted through persistent
      left superior vena cava in patient with Turner's syndrome.
AB  - A 71-year-old woman with Turner's syndrome underwent pacemaker implantation for
      complete atrio-ventricular block. During the procedure, the persistence of left
      sided superior vena cava (LSVC) was observed such that the lead, through the
      coronary sinus, reached the right atrium. By use of stylets, we could drive the
      lead against the lateral atrial wall and curve it through the tricuspid valve
      into the right ventricle. The tip reached an apical stable position, obtaining
      proper stimulation values. Moreover, the VDD dipole was positioned against high
      lateral atrial wall, adequately sensing the atrial potential. So, we could obtain
      an atrial synchronous ventricular pacing with only one VDD lead.

PMID- 17038153
TI  - Appropriate result from an inappropriate ICD shock.
AB  - A case of inappropriate detection of an ungrounded external AC current by an
      implantable cardioverter defibrillator (ICD) is reported. The resultant ICD shock
      dislodged the patient from the electrical source, thus preventing injury or
      electrocution.

PMID- 17038155
TI  - "Wide QRS complex tachycardia in a patient with a minute ventilation (MV) rate
      responsive pacemaker".

PMID- 17038156
TI  - "Viewpoint: fast-track training of non-electrophysiologists to implant
      defibrillators: is it needed?".

PMID- 17038157
TI  - Handball injuries during major international tournaments.
AB  - BACKGROUND: Several authors have analyzed the incidence of handball injuries in
      amateur players but information of handball injury in top-level players is very
      limited. The aim of the study was to analyze the incidence, circumstances and
      characteristics of handball injuries during major international tournaments.
      METHODS: Injuries during six international handball tournaments were analyzed,
      using an established injury report system. The physicians of all participating
      teams were asked to report all injuries after each match on a standardized injury
      report form. The response rate was on average 87%. RESULTS: The incidence of
      injury was on average 108 injuries/1000 player hours (95% confidence interval
      (CI): 98-117) or 1.5 injuries/match (95% CI: 1.4-1.6). The injuries affected most
      frequently the lower extremity (42%), followed by injuries of the head (23%),
      upper extremity (18%) and trunk (14%). The most frequent diagnosis was contusion
      of head (14%) or ankle sprain (8%). The majority of injuries were caused by
      contact with another player. The incidence of time loss injuries was on average
      27/1000 player hours (95% CI: 22-32), and significantly higher in men than in
      women. CONCLUSION: Preventive program proven effective should be implemented.
      Fair Play is an essential aspect of injury prevention. Therefore, close
      cooperation with the referees is also necessary to make handball a safer sport.

PMID- 17038158
TI  - Self-guided brisk walking training with or without poles: a randomized-controlled
      trial in middle-aged women.
AB  - Walking with poles (Nordic walking, NW) has become popular. We compared training
      responses of brisk walking (W) or NW on cardiorespiratory and neuromuscular
      fitness. We randomized 121 non-obese sedentary women (aged 50-60) to an NW or W
      group (NWG, WG), to train 40 min four times weekly for 13 weeks. Intensity was
      based on subjective perception of exertion. Cardiorespiratory performance was
      assessed in four levels corresponding to 50%, 65%, 80% and 100% of peak VO(2).
      Fifty-four NWG and 53 WG subjects completed the study. The mean intensity was
      about 50% of heart rate (HR) reserve. The baseline peak VO(2) was 25.8 (SD 3.9)
      mL/min/kg. Both groups improved peak VO(2) similarly (NWG 2.5 mL/min/kg, 95%
      confidence interval (CI) 1.9-3.3; WG 2.6, CI 1.9-3.3). In the submaximal stages
      while walking with or without poles, HR and lactate decreased after training in
      both groups, but the changes were not statistically significantly different
      between the groups. Of the neuromuscular tests after training, the only
      significant difference between the groups was in the leg strength in the one-leg
      squat, favoring WG. In conclusion, both training modes improved similarly health
      enhancing physical fitness, and they were feasible and safe.

PMID- 17038159
TI  - Strength training effects of whole-body vibration?
AB  - Whole-body vibration (WBV) has been suggested to have a beneficial effect on
      muscle strength. Manufacturers of vibration platforms promote WBV as an effective
      alternative or complement to resistance training. This study aimed to review
      systematically the current (August 2005) scientific support for effects of WBV on
      muscle strength and jump performance. MEDLINE and SPORT DISCUS were searched for
      the word vibration in combination with strength or training. Twelve articles were
      included in the final analysis. In four of the five studies that used an adequate
      design with a control group performing the same exercises as the WBV group, no
      difference in performance improvement was found between groups, suggesting no or
      only minor additional effects of WBV as such. Proposed neural mechanisms are
      discussed.

PMID- 17038160
TI  - Plasma fibrinogen gamma' chain content in the thrombotic microangiopathy
      syndrome.
AB  - BACKGROUND: Human fibrinogen gamma chain variants, termed gamma' chains, contain
      a unique 20-residue sequence after gamma chain residue 407 that ends at
      gamma'427, and is designated gamma'(427L). Full-length (FL) gamma'(427L) chains
      are constituents of a fibrin-dependent thrombin inhibitory system known as
      antithrombin I, whereas a gamma' chain processed in vivo, termed gamma'(423P),
      lacks the C-terminal tetrapeptide EDDL, and does not bind thrombin. Together, the
      gamma'(423P) and gamma'(427L) chains comprise the total plasma fibrinogen gamma'
      chain content. OBJECTIVES: Lowered plasma gamma' chain content (i.e. gamma' chain
      containing fibrinogen/total fibrinogen ratio) has been shown to correlate with
      susceptibility to venous thrombosis, thus prompting this study on the total and
      FL gamma' chain content in 45 subjects with thrombotic microangiopathy (TMA), a
      disorder characterized by microvascular thrombosis. METHODS: We measured by
      enzyme-linked immunosorbent assay the total gamma' chain-containing
      fibrinogen/total fibrinogen (Total gamma'-fgn/Total fgn) ratio and the FL gamma'
      chain-containing fibrinogen/total fibrinogen (FL gamma'-fgn/Total fgn) ratio in
      these plasmas and in healthy subjects (n = 87). RESULTS: In healthy subjects, the
      mean Total gamma'-fgn/Total fgn ratio was 0.127, whereas the FL gamma'-fgn/Total
      fgn ratio was somewhat lower at 0.099 (P < 0.0001), a difference reflecting the
      presence of gamma'(423P) chains. In TMA plasmas, both the Total gamma'-fgn and FL
      gamma'-fgn/Total fgn ratios (0.099 and 0.084, respectively) were lower than those
      of their healthy subject counterparts (P < 0.0001). CONCLUSIONS: These findings
      in TMA suggest that reductions in the gamma' chain content indicate reduced
      antithrombin I activity that may contribute to microvascular thrombosis in TMA.

PMID- 17038161
TI  - My life with tissue factor.

PMID- 17038162
TI  - Heterologous expression of lcc1 gene from Trametes trogii in Pichia pastoris and
      characterization of the recombinant enzyme.
AB  - BACKGROUND: Fungal laccases are useful enzymes for industrial applications; they
      exhibit broad substrate specificity and thus are able to oxidize a variety of
      xenobiotic compounds including chlorinated phenolics, synthetic dyes, pesticides
      and polycyclic aromatic hydrocarbons. Unfortunately, the biotechnological
      exploitation of laccases can be hampered by the difficulties concerning the
      enzyme production by the native hosts. RESULTS: In order to obtain a simple and
      efficient source of laccase, the lcc1 cDNA isolated from the white-rot fungus
      Trametes trogii has been successfully expressed in the methylotrophic yeast
      Pichia pastoris under the control of the methanol induced alcohol oxidase
      promoter PAOX1. The recombinant Lcc1 was produced as a secreted protein with the
      native N-terminal prepropeptide for signal trafficking, and thus easily recovered
      from the culture medium. At the 1-liter scale, as calculated on the basis of the
      specific activity, the recombinant protein was produced at a yield of 17 mg/l.
      The highest production level obtained in fed-batch culture was 2520 U/l,
      corresponding to a specific productivity of 31.5 U/g biomass. The purified
      recombinant laccase exhibited a behaviour similar to the main laccase produced by
      T. trogii. Lcc1 showed high activity in the presence of organic solvents and a
      high decolourization capacity towards azo, triarylmethane, indigo carmine and
      anthraquinonic dyes, that could be significantly enhanced in the presence of the
      redox mediators 1-hydroxybenzotriazole and violuric acid. CONCLUSION:
      Heterologous expression of T. trogii laccase lcc1 in the methylotrophic yeast P.
      pastoris was successfully achieved. The biochemical and kinetic characterization
      of the recombinant protein suggests potential technological applications for this
      enzyme.

PMID- 17038164
TI  - Analysis of optimal phenotypic space using elementary modes as applied to
      Corynebacterium glutamicum.
AB  - BACKGROUND: Quantification of the metabolic network of an organism offers
      insights into possible ways of developing mutant strain for better productivity
      of an extracellular metabolite. The first step in this quantification is the
      enumeration of stoichiometries of all reactions occurring in a metabolic network.
      The structural details of the network in combination with experimentally observed
      accumulation rates of external metabolites can yield flux distribution at steady
      state. One such methodology for quantification is the use of elementary modes,
      which are minimal set of enzymes connecting external metabolites. Here, we have
      used a linear objective function subject to elementary modes as constraint to
      determine the fluxes in the metabolic network of Corynebacterium glutamicum. The
      feasible phenotypic space was evaluated at various combinations of oxygen and
      ammonia uptake rates. RESULTS: Quantification of the fluxes of the elementary
      modes in the metabolism of C. glutamicum was formulated as linear programming.
      The analysis demonstrated that the solution was dependent on the criteria of
      objective function when less than four accumulation rates of the external
      metabolites were considered. The analysis yielded feasible ranges of fluxes of
      elementary modes that satisfy the experimental accumulation rates. In C.
      glutamicum, the elementary modes relating to biomass synthesis through glycolysis
      and TCA cycle were predominantly operational in the initial growth phase. At a
      later time, the elementary modes contributing to lysine synthesis became active.
      The oxygen and ammonia uptake rates were shown to be bounded in the phenotypic
      space due to the stoichiometric constraint of the elementary modes. CONCLUSION:
      We have demonstrated the use of elementary modes and the linear programming to
      quantify a metabolic network. We have used the methodology to quantify the
      network of C. glutamicum, which evaluates the set of operational elementary modes
      at different phases of fermentation. The methodology was also used to determine
      the feasible solution space for a given set of substrate uptake rates under
      specific optimization criteria. Such an approach can be used to determine the
      optimality of the accumulation rates of any metabolite in a given network.

PMID- 17038163
TI  - Testing statistical significance scores of sequence comparison methods with
      structure similarity.
AB  - BACKGROUND: In the past years the Smith-Waterman sequence comparison algorithm
      has gained popularity due to improved implementations and rapidly increasing
      computing power. However, the quality and sensitivity of a database search is not
      only determined by the algorithm but also by the statistical significance testing
      for an alignment. The e-value is the most commonly used statistical validation
      method for sequence database searching. The CluSTr database and the Protein World
      database have been created using an alternative statistical significance test: a
      Z-score based on Monte-Carlo statistics. Several papers have described the
      superiority of the Z-score as compared to the e-value, using simulated data. We
      were interested if this could be validated when applied to existing, evolutionary
      related protein sequences. RESULTS: All experiments are performed on the ASTRAL
      SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value
      and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST
      and FASTA algorithms are used as reference. We find that two out of three Smith
      Waterman implementations with e-value are better at predicting structural
      similarities between proteins than the Smith-Waterman implementation with Z
      score. SSEARCH especially has very high scores. CONCLUSION: The compute intensive
      Z-score does not have a clear advantage over the e-value. The Smith-Waterman
      implementations give generally better results than their heuristic counterparts.
      We recommend using the SSEARCH algorithm combined with e-values for pairwise
      sequence comparisons.

PMID- 17038165
TI  - Statistical measures for defining an individual's degree of independence within
      state-dependent dynamic games.
AB  - BACKGROUND: For organisms living or interacting in groups, the decision-making
      processes of an individual may be based upon aspects of both its own state and
      the states of other organisms around it. Much research has sought to determine
      how group decisions are made, and whether some individuals are more likely to
      influence these decisions than others. State-dependent modelling techniques are a
      powerful tool for exploring group decision-making processes, but analyses
      conducted so far have lacked methods for identifying how dependent an
      individual's actions are on the rest of the group. RESULTS: Here, we introduce
      and evaluate two easy-to-calculate statistics that quantify how dependent an
      individual's actions are upon the state of a co-player in a two-player state
      dependent dynamic game. We discuss the merits of these statistics, and situations
      in which they would be useful. CONCLUSION: Our statistical measures provide a
      means of quantifying how independent an individual's actions are. They also allow
      researchers to quantify the output of state-dependent dynamic games, and
      quantitatively assess the predictions of these models.

PMID- 17038166
TI  - Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with
      pneumococcal meningitis: a prospective cohort study.
AB  - BACKGROUND: A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been
      identified as an independent risk factor for adverse outcome in adults with
      bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with
      early meningitis in patients with meningococcal infections, the relation between
      CSF WBC and outcome in patients with pneumococcal meningitis is not understood.
      METHODS: We examined the relation between CSF WBC, bacteraemia and sepsis in a
      prospective cohort study that included 352 episodes of pneumococcal meningitis,
      confirmed by CSF culture, occurring in patients aged >16 years. RESULTS: CSF WBC
      was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3
      (interquartile range 531-6983 per mm3) and 104 patients (33%) had a CSF WBC
      <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an
      unfavourable outcome (defined as a Glasgow Outcome Scale score of 1-4) than those
      with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was
      significantly associated with blood WBC (Spearman's test 0.29), CSF protein level
      (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C
      reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had
      a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more
      often developed systemic complications (cardiorespiratory failure, sepsis) than
      those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a
      multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22,
      95%CI 1.02-1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17-5.14),
      and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments
      0.67, 95% CI 0.47-0.97) were associated with a CSF WBC <1000/mm3. CONCLUSION: A
      low CSF WBC in adults with pneumococcal meningitis is related to the presence of
      signs of sepsis and systemic complications. Invasive pneumococcal infections
      should possibly be regarded as a continuum from meningitis to sepsis.

PMID- 17038167
TI  - Storage protein profiles in Spanish and runner market type peanuts and potential
      markers.
AB  - BACKGROUND: Proteomic analysis has proven to be the most powerful method for
      describing plant species and lines, and for identification of proteins in complex
      mixtures. The strength of this method resides in high resolving power of two
      dimensional electrophoresis (2-DE), coupled with highly sensitive mass
      spectrometry (MS), and sequence homology search. By using this method, we might
      find polymorphic markers to differentiate peanut subspecies. RESULTS: Total
      proteins extracted from seeds of 12 different genotypes of cultivated peanut
      (Arachis hypogaea L.), comprised of runner market (A. hypogaea ssp. hypogaea) and
      Spanish-bunch market type (A. hypogaea ssp. fastigiata), were separated by
      electrophoresis on both one- and two-dimensional SDS-PAGE gels. The protein
      profiles were similar on one-dimensional gels for all tested peanut genotypes.
      However, peanut genotype A13 lacked one major band with a molecular weight of
      about 35 kDa. There was one minor band with a molecular weight of 27 kDa that was
      present in all runner peanut genotypes and the Spanish-derivatives (GT-YY7, GT
      YY20, and GT-YY79). The Spanish-derivatives have a runner-type peanut in their
      pedigrees. The 35 kDa protein in A13 and the 27 kDa protein in runner-type peanut
      genotypes were confirmed on the 2-D SDS-PAGE gels. Among more than 150 main
      protein spots on the 2-D gels, four protein spots that were individually marked
      as spots 1-4 showed polymorphic patterns between runner-type and Spanish-bunch
      peanuts. Spot 1 (ca. 22.5 kDa, pI 3.9) and spot 2 (ca. 23.5 kDa, pI 5.7) were
      observed in all Spanish-bunch genotypes, but were not found in runner types. In
      contrast, spot 3 (ca. 23 kDa, pI 6.6) and spot 4 (ca. 22 kDa, pI 6.8) were
      present in all runner peanut genotypes but not in Spanish-bunch genotypes. These
      four protein spots were sequenced. Based on the internal and N-terminal amino
      acid sequences, these proteins are isoforms (iso-Ara h3) of each other, are iso
      allergens and may be modified by post-translational cleavage. CONCLUSION: These
      results suggest that there may be an association between these polymorphic
      storage protein isoforms and peanut subspecies fastigiata (Spanish type) and
      hypogaea (runner type). The polymorphic protein peptides distinguished by 2-D
      PAGE could be used as markers for identification of runner and Spanish peanuts.

PMID- 17038168
TI  - CpGcluster: a distance-based algorithm for CpG-island detection.
AB  - BACKGROUND: Despite their involvement in the regulation of gene expression and
      their importance as genomic markers for promoter prediction, no objective
      standard exists for defining CpG islands (CGIs), since all current approaches
      rely on a large parameter space formed by the thresholds of length, CpG fraction
      and G+C content. RESULTS: Given the higher frequency of CpG dinucleotides at
      CGIs, as compared to bulk DNA, the distance distributions between neighboring
      CpGs should differ for bulk and island CpGs. A new algorithm (CpGcluster) is
      presented, based on the physical distance between neighboring CpGs on the
      chromosome and able to predict directly clusters of CpGs, while not depending on
      the subjective criteria mentioned above. By assigning a p-value to each of these
      clusters, the most statistically significant ones can be predicted as CGIs.
      CpGcluster was benchmarked against five other CGI finders by using a test
      sequence set assembled from an experimental CGI library. CpGcluster reached the
      highest overall accuracy values, while showing the lowest rate of false-positive
      predictions. Since a minimum-length threshold is not required, CpGcluster can
      find short but fully functional CGIs usually missed by other algorithms. The CGIs
      predicted by CpGcluster present the lowest degree of overlap with Alu
      retrotransposons and, simultaneously, the highest overlap with vertebrate
      Phylogenetic Conserved Elements (PhastCons). CpGcluster's CGIs overlapping with
      the Transcription Start Site (TSS) show the highest statistical significance, as
      compared to the islands in other genome locations, thus qualifying CpGcluster as
      a valuable tool in discriminating functional CGIs from the remaining islands in
      the bulk genome. CONCLUSION: CpGcluster uses only integer arithmetic, thus being
      a fast and computationally efficient algorithm able to predict statistically
      significant clusters of CpG dinucleotides. Another outstanding feature is that
      all predicted CGIs start and end with a CpG dinucleotide, which should be
      appropriate for a genomic feature whose functionality is based precisely on CpG
      dinucleotides. The only search parameter in CpGcluster is the distance between
      two consecutive CpGs, in contrast to previous algorithms. Therefore, none of the
      main statistical properties of CpG islands (neither G+C content, CpG fraction nor
      length threshold) are needed as search parameters, which may lead to the high
      specificity and low overlap with spurious Alu elements observed for CpGcluster
      predictions.

PMID- 17038169
TI  - Influence of parental employment status on Dutch and Slovak adolescents' health.
AB  - BACKGROUND: Recent research shows the possibility that the link between parental
      employment status and children's health can be affected by different cultural or
      societal settings. The aim of this study was to explore whether the effect of
      father's and mother's employment status on several aspects of adolescents' health
      differs between Slovakia and the Netherlands. METHODS: Two data sets were used:
      2616 Slovak adolescents (mean age 14.9) and 2054 Dutch adolescents (mean age
      16.3). Self-rated health, GHQ-12, long-term well-being and Rosenberg self-esteem
      scale were used to assess the health of adolescents. Parental employment status
      was classified into the following categories: employed, unemployed, disabled,
      housewife (among mothers only). Logistic regression analyses were done separately
      for males and females. RESULTS: Results indicate that having an unemployed father
      negatively influences self-rated health and long-term well-being of Slovak male
      adolescents, but has no effect on the health of Dutch adolescents. Secondly,
      having a disabled father has a negative effect on the psychological well-being of
      Dutch males and the self-rated health of females, but does not influence the
      health of Slovak adolescents. Thirdly, having a mother who is disabled,
      unemployed or a housewife has a negative effect on the self-esteem of Slovak
      adolescents. Fourthly, Dutch males whose mother was a housewife had worse long
      term well-being than those with an unemployed mother, whereas Dutch females whose
      mother was a housewife reported better psychological well-being than those with
      an employed mother. CONCLUSION: To conclude briefly our results, father's
      unemployment seems to be a better predictor of health for Slovak adolescents,
      father's disablement of health for Dutch ones. Mother's employment status seemed
      to be important for the self-esteem of Slovak adolescents and mother as a
      housewife for the health of Dutch ones. This suggests that the link between
      parental employment status and the health of their children may vary between
      countries, and therefore further studies involving various cultures are needed.

PMID- 17038170
TI  - African-American mitochondrial DNAs often match mtDNAs found in multiple African
      ethnic groups.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) haplotypes have become popular tools for
      tracing maternal ancestry, and several companies offer this service to the
      general public. Numerous studies have demonstrated that human mtDNA haplotypes
      can be used with confidence to identify the continent where the haplotype
      originated. Ideally, mtDNA haplotypes could also be used to identify a particular
      country or ethnic group from which the maternal ancestor emanated. However, the
      geographic distribution of mtDNA haplotypes is greatly influenced by the movement
      of both individuals and population groups. Consequently, common mtDNA haplotypes
      are shared among multiple ethnic groups. We have studied the distribution of
      mtDNA haplotypes among West African ethnic groups to determine how often mtDNA
      haplotypes can be used to reconnect Americans of African descent to a country or
      ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA
      hypervariable segment I (HVS-I) usually provides sufficient information to assign
      a particular mtDNA to the proper haplogroup, and it contains most of the
      variation that is available to distinguish a particular mtDNA haplotype from
      closely related haplotypes. In this study, samples of general African-American
      and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of
      HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches
      recorded for each sample. RESULTS: When two independent African-American samples
      were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly
      matched common haplotypes that were shared among multiple African ethnic groups.
      Another 40% did not match any sequence in the database, and fewer than 10% were
      an exact match to a sequence from a single African ethnic group. Differences in
      the regional distribution of haplotypes were observed in the African database,
      and the African-American haplotypes were more likely to match haplotypes found in
      ethnic groups from West or West Central Africa than those found in eastern or
      southern Africa. Fewer than 14% of the African-American mtDNA sequences matched
      sequences from only West Africa or only West Central Africa. CONCLUSION: Our
      database of sub-Saharan mtDNA sequences includes the most common haplotypes that
      are shared among ethnic groups from multiple regions of Africa. These common
      haplotypes have been found in half of all sub-Saharan Africans. More than 60% of
      the remaining haplotypes differ from the common haplotypes at a single nucleotide
      position in the HVS-I region, and they are likely to occur at varying frequencies
      within sub-Saharan Africa. However, the finding that 40% of the African-American
      mtDNAs analyzed had no match in the database indicates that only a small fraction
      of the total number of African haplotypes has been identified. In addition, the
      finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences
      from a single African region suggests that few African Americans might be able to
      trace their mtDNA lineages to a particular region of Africa, and even fewer will
      be able to trace their mtDNA to a single ethnic group. However, no firm
      conclusions should be made until a much larger database is available. It is
      clear, however, that when identical mtDNA haplotypes are shared among many ethnic
      groups from different parts of Africa, it is impossible to determine which single
      ethnic group was the source of a particular maternal ancestor based on the mtDNA
      sequence.

PMID- 17038171
TI  - Statistical inference of chromosomal homology based on gene colinearity and
      applications to Arabidopsis and rice.
AB  - BACKGROUND: The identification of chromosomal homology will shed light on such
      mysteries of genome evolution as DNA duplication, rearrangement and loss. Several
      approaches have been developed to detect chromosomal homology based on gene
      synteny or colinearity. However, the previously reported implementations lack
      statistical inferences which are essential to reveal actual homologies. RESULTS:
      In this study, we present a statistical approach to detect homologous chromosomal
      segments based on gene colinearity. We implement this approach in a software
      package ColinearScan to detect putative colinear regions using a dynamic
      programming algorithm. Statistical models are proposed to estimate proper
      parameter values and evaluate the significance of putative homologous regions.
      Statistical inference, high computational efficiency and flexibility of input
      data type are three key features of our approach. CONCLUSION: We apply
      ColinearScan to the Arabidopsis and rice genomes to detect duplicated regions
      within each species and homologous fragments between these two species. We find
      many more homologous chromosomal segments in the rice genome than previously
      reported. We also find many small colinear segments between rice and Arabidopsis
      genomes.

PMID- 17038172
TI  - New insight into the role of phosphodiesterase 3A in porcine oocyte maturation.
AB  - BACKGROUND: The ovulatory surge of gonadotropins triggers oocyte maturation and
      rupture of the ovarian follicle. The resumption of nuclear maturation in the
      oocyte from the prophase stage is characterized by germinal vesicle breakdown
      (GVBD). It has previously been shown that specific inhibition of cAMP degradation
      by PDE3 prevents the resumption of oocyte meiosis. However, no report has
      characterized the activity of PDE3 in the porcine oocyte, or the implication of
      the cAMP-PDE3 pathway in the entire nuclear maturation process. In this study,
      PDE3 activity in the oocyte was assessed during in vitro maturation (IVM) and the
      possible roles of the cAMP-PDE3 pathway in the resumption and progression of
      meiosis were investigated in terms of different models of oocyte maturation.
      RESULTS: Cyclic AMP-degrading PDE activity was detected in the cumulus-oocyte
      complex (COC) and was partially inhibited by a specific PDE3 inhibitor,
      cilostamide. When measured only in the denuded oocyte, PDE activity was almost
      completely inhibited by cilostamide, suggesting that cAMP-PDE3 activity is the
      major cAMP-PDE in porcine oocytes. PDE3A mRNA was detected by RT-PCR. PDE3
      activity did not vary significantly during the early hours of IVM, but a maximum
      was observed at 13 hours. In cumulus-oocyte complexes, meiosis resumed after
      20.81 hours of culture. PDE3 inhibition no longer maintained meiotic arrest if
      sustained beyond 17.65 hours of IVM, 3 hours prior to resumption of meiosis.
      Thereafter, PDE3 inhibition progressively lost its efficacy in GVBD. When the
      protein phosphatase 1 and 2A inhibitor okadaic acid was continuously or
      transiently (3 hours) present during IVM, meiosis resumed prematurely; PDE3
      inhibition was unable to prevent GVBD. However, PDE3 inhibition in COC treated
      with OA for 3 hours significantly delayed meiosis at the intermediate stage.
      CONCLUSION: The present investigation has demonstrated that PDE3A is the major
      cAMP-degrading PDE in the oocyte. It regulates the resumption of meiosis until 3
      hours prior to GVBD and transiently affects meiotic progression.

PMID- 17038174
TI  - Gene function classification using Bayesian models with hierarchy-based priors.
AB  - BACKGROUND: We investigate whether annotation of gene function can be improved
      using a classification scheme that is aware that functional classes are organized
      in a hierarchy. The classifiers look at phylogenic descriptors, sequence based
      attributes, and predicted secondary structure. We discuss three Bayesian models
      and compare their performance in terms of predictive accuracy. These models are
      the ordinary multinomial logit (MNL) model, a hierarchical model based on a set
      of nested MNL models, and an MNL model with a prior that introduces correlations
      between the parameters for classes that are nearby in the hierarchy. We also
      provide a new scheme for combining different sources of information. We use these
      models to predict the functional class of Open Reading Frames (ORFs) from the E.
      coli genome. RESULTS: The results from all three models show substantial
      improvement over previous methods, which were based on the C5 decision tree
      algorithm. The MNL model using a prior based on the hierarchy outperforms both
      the non-hierarchical MNL model and the nested MNL model. In contrast to previous
      attempts at combining the three sources of information in this dataset, our new
      approach to combining data sources produces a higher accuracy rate than applying
      our models to each data source alone. CONCLUSION: Together, these results show
      that gene function can be predicted with higher accuracy than previously
      achieved, using Bayesian models that incorporate suitable prior information.

PMID- 17038175
TI  - Differences in polyadenylation site choice between somatic and male germ cells.
AB  - BACKGROUND: We have previously noted that there were differences in somatic and
      male germ cell polyadenylation site choices. First, male germ cells showed a
      lower incidence of the sequence AAUAAA (an important element for somatic
      polyadenylation site choice) near the polyadenylation site choice. Second, the
      polyadenylation sites chosen in male germ cells tended to be nearer the 5' end of
      the mRNA than those chosen in somatic cells. Finally, a number of mRNAs used a
      different polyadenylation site in male germ cells than in somatic cells. These
      differences suggested that male germ cell-specific polyadenylation sites may be
      poor substrates for polyadenylation in somatic cells. We therefore hypothesized
      that male germ cell-specific polyadenylation sites would be inefficiently used in
      somatic cells. RESULTS: We tested whether pre-mRNA sequences surrounding male
      germ cell-specific polyadenylation sites (polyadenylation cassettes) could be
      used to direct polyadenylation efficiently in somatic cells. To do this, we
      developed a luciferase reporter system in which luciferase activity correlated
      with polyadenylation efficiency. We showed that in somatic cells, somatic
      polyadenylation cassettes were efficiently polyadenylated, while male germ cell
      specific polyadenylation cassettes were not. We also developed a sensitive, 3'
      RACE-based assay to analyze polyadenylation site choice. Using this assay, we
      demonstrated that male germ cell-specific polyadenylation cassettes were not
      polyadenylated at the expected site in somatic cells, but rather at aberrant
      sites upstream of the sites used in male germ cells. Finally, mutation of the
      male germ cell-specific poly(A) signal to a somatic poly(A) signal resulted in
      more efficient polyadenylation in somatic cells. CONCLUSION: These data suggest
      that regulated polyadenylation site choice of male germ cell-specific
      polyadenylation sites requires one or more factors that are absent from somatic
      cells.

PMID- 17038176
TI  - Integrative missing value estimation for microarray data.
AB  - BACKGROUND: Missing value estimation is an important preprocessing step in
      microarray analysis. Although several methods have been developed to solve this
      problem, their performance is unsatisfactory for datasets with high rates of
      missing data, high measurement noise, or limited numbers of samples. In fact,
      more than 80% of the time-series datasets in Stanford Microarray Database contain
      less than eight samples. RESULTS: We present the integrative Missing Value
      Estimation method (iMISS) by incorporating information from multiple reference
      microarray datasets to improve missing value estimation. For each gene with
      missing data, we derive a consistent neighbor-gene list by taking reference data
      sets into consideration. To determine whether the given reference data sets are
      sufficiently informative for integration, we use a submatrix imputation approach.
      Our experiments showed that iMISS can significantly and consistently improve the
      accuracy of the state-of-the-art Local Least Square (LLS) imputation algorithm by
      up to 15% improvement in our benchmark tests. CONCLUSION: We demonstrated that
      the order-statistics-based integrative imputation algorithms can achieve
      significant improvements over the state-of-the-art missing value estimation
      approaches such as LLS and is especially good for imputing microarray datasets
      with a limited number of samples, high rates of missing data, or very noisy
      measurements. With the rapid accumulation of microarray datasets, the performance
      of our approach can be further improved by incorporating larger and more
      appropriate reference datasets.

PMID- 17038177
TI  - The association between indwelling urinary catheter use in the elderly and
      urinary tract infection in acute care.
AB  - BACKGROUND: The use of indwelling urinary catheters (IUCs) is thought to be the
      most significant risk factor for developing nosocomial urinary tract infections
      (UTIs). However, it is unclear how many elderly patients have preexisting
      bacteriuria prior to IUC placement. The purpose of this study was to determine 1)
      the frequency and appropriateness of IUC use in the Emergency Department (ED) in
      elderly patients admitted to our acute care hospital, 2) the percentage of
      elderly patients with an IUC who were discharged from the hospital with a
      diagnosis of UTI, 3) the percentage of patients with IUCs who were diagnosed and
      treated for UTI in the ED or who had admission bacteriuria > or =105 organisms/ml
      indicating preexisting UTI, and 4) the percentage of patients with no indication
      of UTI on admission who had inappropriately placed IUCs and subsequently were
      diagnosed with a UTI. METHODS: Retrospective chart review. Chi square used to
      test significance of differences in proportions. RESULTS: Seventy three percent
      of patients who received an IUC in the ED were elderly (> or =65 years old).
      During the study period, 277 elderly patients received an IUC prior to admission.
      Of these, 77 (28%) were diagnosed with UTI during their hospitalization. Fifty
      three (69%) of those diagnosed with a UTI by discharge either had the UTI
      diagnosed in the ED or had bacteriuria > or =105 organisms/ml prior to IUC
      placement. Of the 24 elderly patients who developed a catheter-associated UTI
      (i.e., 9% of the elderly population who received an IUC), 11 of the IUCs were
      placed inappropriately. Thus, 4% of elderly patients with no indication of UTI on
      admission who received an inappropriate IUC in the ED had a primary or secondary
      diagnosis of UTI by discharge. The overall rate of nosocomial UTI due to an
      inappropriately placed IUC was the same in males and females. CONCLUSION: This
      study indicates that the strong association between IUC use and UTI may be partly
      explained by the high prevalence of preexisting UTI prior to IUC placement.
      Further prospective studies are needed to clarify the true risk vs benefit ratio
      for IUC use in acutely ill elderly patients.

PMID- 17038178
TI  - Evolution of competence and DNA uptake specificity in the Pasteurellaceae.
AB  - BACKGROUND: Many bacteria can take up DNA, but the evolutionary history and
      function of natural competence and transformation remain obscure. The sporadic
      distribution of competence suggests it is frequently lost and/or gained, but this
      has not been examined in an explicitly phylogenetic context. Additional insight
      may come from the sequence specificity of uptake by species such as Haemophilus
      influenzae, where a 9 bp uptake signal sequence (USS) repeat is both highly
      overrepresented in the genome and needed for efficient DNA uptake. We used the
      distribution of competence genes and DNA uptake specificity in H. influenzae's
      family, the Pasteurellaceae, to examine the ancestry of competence. RESULTS: A
      phylogeny of the Pasteurellaceae based on 12 protein coding genes from species
      with sequenced genomes shows two strongly supported subclades: the Hin subclade
      (H. influenzae, Actinobacillus actinomycetemcomitans, Pasteurella multocida,
      Mannheimia succiniciproducens, and H. somnus), and the Apl subclade (A.
      pleuropneumoniae, M. haemolytica, and H. ducreyi). All species contained
      homologues of all known H. influenzae competence genes, consistent with an
      ancestral origin of competence. Competence gene defects were identified in three
      species (H. somnus, H. ducreyi and M. haemolytica); each appeared to be of recent
      origin. The assumption that USS arise by mutation rather than copying was first
      confirmed using alignments of H. influenzae proteins with distant homologues.
      Abundant USS-like repeats were found in all eight Pasteurellacean genomes; the
      repeat consensuses of species in the Hin subclade were identical to that of H.
      influenzae (AAGTGCGGT), whereas members of the Apl subclade shared the consensus
      ACAAGCGGT. All species' USSs had the strong consensus and flanking AT-rich
      repeats of H. influenzae USSs. DNA uptake and competition experiments
      demonstrated that the Apl-type repeat is a true USS distinct from the Hin-type
      USS: A. pleuropneumoniae preferentially takes up DNA fragments containing the Apl
      type USS over both H. influenzae and unrelated DNAs, and H. influenzae prefers
      its own USS over the Apl type. CONCLUSION: Competence and DNA uptake specificity
      are ancestral properties of the Pasteurellaceae, with divergent USSs and uptake
      specificity distinguishing only the two major subclades. The conservation of most
      competence genes over the approximately 350 million year history of the family
      suggests that lineages that lose competence may be evolutionary dead ends.

PMID- 17038179
TI  - Case report of right hamate hook fracture in a patient with previous fracture
      history of left hamate hook: is it hamate bipartite?
AB  - BACKGROUND: Hamate hook fracture is a common fracture in golfers and others who
      play sports that involve rackets or sticks such as tennis or hockey. This patient
      had a previous hamate fracture in the opposing wrist along with potential
      features of hamate bipartite. CASE PRESENTATION: A 19 year old male presented
      with a complaint of right wrist pain on the ulnar side of the wrist with no
      apparent mechanism of injury. The pain came on gradually one week before being
      seen in the office and he reported no prior care for the complaint. His history
      includes traumatic left hamate hook fracture with surgical excision. CONCLUSION:
      The patient was found to have marked tenderness over the hamate and with a prior
      fracture to the other wrist, computed tomography of the wrist was ordered
      revealing a fracture to the hamate hook in the right wrist. He was referred for
      surgical evaluation and the hook of the hamate was excised. Post-surgically, the
      patient was able to return to normal activity within eight weeks. This case is
      indicative of fracture rather than hamate bipartite. This fracture should be
      considered in a case of ulnar sided wrist pain where marked tenderness is noted
      over the hamate, especially after participation in club or racket sports.

PMID- 17038180
TI  - The Council on Chiropractic Education's new wellness standard: a call to action
      for the chiropractic profession.
AB  - BACKGROUND: The chiropractic profession has long considered itself to be a
      preventive science. Recently the Council on Chiropractic Education (CCE) has
      defined a set of standards that must be implemented at all US chiropractic
      colleges as of January of 2007. These are specific to wellness measures and
      health promoting efforts that should be performed by chiropractors. This will
      mandate traditional health promotion and prevention methods be taught to students
      at accredited colleges and to practicing chiropractors. OBJECTIVE: To present the
      idea of performing traditional health promotion and wellness-concepts in
      chiropractic practice as a call to action for clinicians and generate discussion
      on the topic. DISCUSSION: This manuscript discusses relevant topics of health
      promotion and prevention for chiropractors and other practicing clinicians that
      should be made priorities with patients in order to enhance both patient health
      and community and population health. CONCLUSION: All practicing chiropractors, as
      well as other clinicians should take these new standards from the CCE as a call
      to action to begin helping patients address the removable causes of morbidity,
      disability and premature mortality where they exist, in addition to treating
      their painful spinal conditions.

PMID- 17038181
TI  - Genepi: a blackboard framework for genome annotation.
AB  - BACKGROUND: Genome annotation can be viewed as an incremental, cooperative, data
      driven, knowledge-based process that involves multiple methods to predict gene
      locations and structures. This process might have to be executed more than once
      and might be subjected to several revisions as the biological (new data) or
      methodological (new methods) knowledge evolves. In this context, although a lot
      of annotation platforms already exist, there is still a strong need for computer
      systems which take in charge, not only the primary annotation, but also the
      update and advance of the associated knowledge. In this paper, we propose to
      adopt a blackboard architecture for designing such a system RESULTS: We have
      implemented a blackboard framework (called Genepi) for developing automatic
      annotation systems. The system is not bound to any specific annotation strategy.
      Instead, the user will specify a blackboard structure in a configuration file and
      the system will instantiate and run this particular annotation strategy. The
      characteristics of this framework are presented and discussed. Specific
      adaptations to the classical blackboard architecture have been required, such as
      the description of the activation patterns of the knowledge sources by using an
      extended set of Allen's temporal relations. Although the system is robust enough
      to be used on real-size applications, it is of primary use to bioinformatics
      researchers who want to experiment with blackboard architectures. CONCLUSION: In
      the context of genome annotation, blackboards have several interesting features
      related to the way methodological and biological knowledge can be updated. They
      can readily handle the cooperative (several methods are implied) and
      opportunistic (the flow of execution depends on the state of our knowledge)
      aspects of the annotation process.

PMID- 17038182
TI  - An educational campaign to increase chiropractic intern advising roles on patient
      smoking cessation.
AB  - BACKGROUND: Tobacco use, particularly smoking, is the most preventable cause of
      death in the United States. More than 400,000 premature deaths are associated
      with its use and the health care costs are in the billions. All health care
      provider groups should be concerned with patients who continue to smoke and use
      tobacco. The US Preventive Services Taskforce and Health People 2010 guidelines
      encourage providers to counsel smokers on cessation. Current studies, though
      limited regarding chiropractic advising practices indicate a low engagement rate
      when it comes to providing cessation information. OBJECTIVE: To test a campaign
      regarding initial impact aimed at increasing chiropractic interns advising on
      cessation and delivery of information to smokers on cessation. DISCUSSION:
      Chiropractic interns do engage patients on smoking status and can be encouraged
      to provide more cessation messages and information to patients. The initial
      impact assessment of this campaign increased the provision of information to
      patients by about 25%. The prevalence of smoking among chiropractic patients,
      particularly at teaching clinics may be lower than the national averages.
      CONCLUSION: Chiropractic interns can and should be encouraged to advise smokers
      about cessation. A systematic method of intake information on smoking status is
      needed and a standardized education protocol for chiropractic colleges is needed.
      Chiropractic colleges should assess the adequacy of their advising roles and
      implement changes to increase cessation messages to their patients as soon as
      possible.

PMID- 17038183
TI  - Cyclophilin A interacts with diverse lentiviral capsids.
AB  - BACKGROUND: The capsid (CA) protein of HIV-1 binds with high affinity to the host
      protein cyclophilin A (CypA). This binding positively affects some early stage of
      the viral life-cycle because prevention of binding either by drugs that occupy
      that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks
      down intracellular CypA level diminishes viral infectivity. The closely related
      lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was
      limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact
      with CypA in a yeast two-hybrid assay. RESULTS: We find that diverse
      lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed
      that an amino acid that is in a homologous position to the proline at amino acid
      90 of HIV-1 CA is essential for FIV interactions with CypA. CONCLUSION: These
      results demonstrate that CypA binding to lentiviruses is more widespread than
      previously thought and suggest that this interaction is evolutionarily important
      for lentiviral infection.

PMID- 17038184
TI  - Joint distribution approaches to simultaneously quantifying benefit and risk.
AB  - BACKGROUND: The benefit-risk ratio has been proposed to measure the tradeoff
      between benefits and risks of two therapies for a single binary measure of
      efficacy and a single adverse event. The ratio is calculated from the difference
      in risk and difference in benefit between therapies. Small sample sizes or
      expected differences in benefit or risk can lead to no solution or problematic
      solutions for confidence intervals. METHODS: Alternatively, using the joint
      distribution of benefit and risk, confidence regions for the differences in risk
      and benefit can be constructed in the benefit-risk plane. The information in the
      joint distribution can be summarized by choosing regions of interest in this
      plane. Using Bayesian methodology provides a very flexible framework for
      summarizing information in the joint distribution. RESULTS: Data from a National
      Institute of Child Health & Human Development trial of hydrocortisone illustrate
      the construction of confidence regions and regions of interest in the benefit
      risk plane, where benefit is survival without supplemental oxygen at 36 weeks
      postmenstrual age, and risk is gastrointestinal perforation. For the subgroup of
      infants exposed to chorioamnionitis the confidence interval based on the benefit
      risk ratio is wide (Benefit-risk ratio: 1.52; 90% confidence interval: 0.23 to
      5.25). Choosing regions of appreciable risk and acceptable risk in the benefit
      risk plane confirms the uncertainty seen in the wide confidence interval for the
      benefit-risk ratio--there is a greater than 50% chance of falling into the region
      of acceptable risk--while visually allowing the uncertainty in risk and benefit
      to be shown separately. Applying Bayesian methodology, an incremental net health
      benefit analysis shows there is a 72% chance of having a positive incremental net
      benefit if hydrocortisone is used in place of placebo if one is willing to incur
      at most one gastrointestinal perforation for each additional infant that survives
      without supplemental oxygen. CONCLUSION: If the benefit-risk ratio is presented,
      the joint distribution of benefit and risk also should be shown. These regions
      avoid the ambiguity associated with collapsing benefit and risk to a single
      dimension. Bayesian methods allow even greater flexibility in simultaneously
      quantifying benefit and risk.

PMID- 17038185
TI  - Integration of curated databases to identify genotype-phenotype associations.
AB  - BACKGROUND: The ability to rapidly characterize an unknown microorganism is
      critical in both responding to infectious disease and biodefense. To do this, we
      need some way of anticipating an organism's phenotype based on the molecules
      encoded by its genome. However, the link between molecular composition (i.e.
      genotype) and phenotype for microbes is not obvious. While there have been
      several studies that address this challenge, none have yet proposed a large-scale
      method integrating curated biological information. Here we utilize a systematic
      approach to discover genotype-phenotype associations that combines phenotypic
      information from a biomedical informatics database, GIDEON, with the molecular
      information contained in National Center for Biotechnology Information's Clusters
      of Orthologous Groups database (NCBI COGs). RESULTS: Integrating the information
      in the two databases, we are able to correlate the presence or absence of a given
      protein in a microbe with its phenotype as measured by certain morphological
      characteristics or survival in a particular growth media. With a 0.8 correlation
      score threshold, 66% of the associations found were confirmed by the literature
      and at a 0.9 correlation threshold, 86% were positively verified. CONCLUSION: Our
      results suggest possible phenotypic manifestations for proteins biochemically
      associated with sugar metabolism and electron transport. Moreover, we believe our
      approach can be extended to linking pathogenic phenotypes with functionally
      related proteins.

PMID- 17038186
TI  - Daily temperature profiles in and around Western Kenyan larval habitats of
      Anopheles gambiae as related to egg mortality.
AB  - BACKGROUND: Anopheles gambiae eggs are more frequently found on soil around
      puddle habitats of the larvae, than on the water surface itself in Western Kenya.
      Thus, eggs can experience temperatures more wide-ranging and lethal than those
      experienced by larvae or pupae confined within puddles. METHODS: Small batches of
      eggs from house-collected An. gambiae as well as from the Kisumu laboratory
      strain were bathed for defined times in water whose temperature was precisely
      controlled. Daily temperature profiles were recorded by an infrared thermometer
      on seven different days in and around three types of typical An. gambiae larval
      habitats at Kisian. RESULTS: For wild eggs, significant mortality occurred upon
      brief heating between 42-44 degrees C. Few eggs hatched after 10 min at 45
      degrees C and none hatched above this temperature. A similar pattern occurred for
      eggs of the Kisumu strain, except it was shifted downwards by 1 degrees C. Egg
      mortality was time-dependent above 40 degrees C. Temperatures of water in the
      three types of larval habitats never exceeded 35 degrees C. Wet or damp mud
      rarely and only briefly exceeded 40 degrees C; thus, water and mud would be
      highly conducive to egg survival and development. However, dry soils frequently
      reached 40-50 degrees C for several h. Eggs stranded on dry surfaces would
      experience substantial mortality on hot, sunny days. CONCLUSION: Moist mud around
      puddles constitutes suitable habitat for An. gambiae eggs; however, eggs on the
      surface of dry soil under direct sunlight are unlikely to survive for more than a
      few hours.

PMID- 17038187
TI  - Laboratory tests of oviposition by the African malaria mosquito, Anopheles
      gambiae, on dark soil as influenced by presence or absence of vegetation.
AB  - BACKGROUND: Physical objects like vegetation can influence oviposition by
      mosquitoes on soil or water substrates. Anopheles gambiae s. l. is generally
      thought to utilize puddles over bare soil as its prime larval habitat and to
      avoid standing water populated with vegetation. In Kisian, Kenya near Kisumu,
      water often pools in grassy drainage areas both during and after periods of
      infrequent rains, when typical puddle habitats become scarce because of drying.
      This raised the question of whether An. gambiae has the behavioural flexibility
      to switch ovipositional sites when puddles over bare soil are unavailable.
      METHODS: To test whether presence and height of grasses influenced oviposition,
      wild-caught gravid An. gambiae s. l. were offered paired choices between wet,
      bare soil and wet soil populated with mixed grasses or grasses of differing
      height. No-choice tests were also conducted by giving females either grassy soil
      or bare soil. RESULTS: In choice tests, females laid four times more eggs on
      bare, wet soil than soil populated with grasses. However in no-choice tests, egg
      output was not significantly different whether grasses were present or not.
      Females laid significantly more eggs on soil populated with short grass than with
      medium, or tall grass. CONCLUSION: This work shows An. gambiae s. l. has the
      capacity to oviposit into grassy aquatic habitats when typical puddles over bare
      soil are unavailable. This knowledge will need to be considered in the design and
      implementation of programmes aimed at reducing malaria transmission by
      suppression of An. gambiae s. l. immatures.

PMID- 17038188
TI  - Structural equation and log-linear modeling: a comparison of methods in the
      analysis of a study on caregivers' health.
AB  - BACKGROUND: In this paper we compare the results in an analysis of determinants
      of caregivers' health derived from two approaches, a structural equation model
      and a log-linear model, using the same data set. METHODS: The data were collected
      from a cross-sectional population-based sample of 468 families in Ontario, Canada
      who had a child with cerebral palsy (CP). The self-completed questionnaires and
      the home-based interviews used in this study included scales reflecting socio
      economic status, child and caregiver characteristics, and the physical and
      psychological well-being of the caregivers. Both analytic models were used to
      evaluate the relationships between child behaviour, caregiving demands, coping
      factors, and the well-being of primary caregivers of children with CP. RESULTS:
      The results were compared, together with an assessment of the positive and
      negative aspects of each approach, including their practical and conceptual
      implications. CONCLUSION: No important differences were found in the substantive
      conclusions of the two analyses. The broad confirmation of the Structural
      Equation Modeling (SEM) results by the Log-linear Modeling (LLM) provided some
      reassurance that the SEM had been adequately specified, and that it broadly
      fitted the data.

PMID- 17038190
TI  - Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
AB  - BACKGROUND: Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an
      important opportunistic human pathogen. Generally, the acquisition of genes in
      the form of pathogenicity islands distinguishes pathogenic isolates from
      nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa,
      PA14, and compared it with a previously sequenced (and less pathogenic) strain,
      PAO1, to identify novel virulence genes. RESULTS: The PA14 and PAO1 genomes are
      remarkably similar, although PA14 has a slightly larger genome (6.5 megabses
      [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are
      absent in PAO1 to determine which of these genes, if any, contribute to its
      enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we
      tested 18 additional diverse strains in the C. elegans model and observed a wide
      range of pathogenic potential; however, genotyping these strains using a custom
      microarray showed that the presence of PA14 genes that are absent in PAO1 did not
      correlate with the virulence of these strains. Second, we utilized a full-genome
      nonredundant mutant library of PA14 to identify five genes (absent in PAO1)
      required for C. elegans killing. Surprisingly, although these five genes are
      present in many other P. aeruginosa strains, they do not correlate with virulence
      in C. elegans. CONCLUSION: Genes required for pathogenicity in one strain of P.
      aeruginosa are neither required for nor predictive of virulence in other strains.
      We therefore propose that virulence in this organism is both multifactorial and
      combinatorial, the result of a pool of pathogenicity-related genes that interact
      in various combinations in different genetic backgrounds.

PMID- 17038189
TI  - Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots
      reveals novel classes of responsive genes.
AB  - BACKGROUND: Roots are an attractive system for genomic and post-genomic studies
      of NaCl responses, due to their primary importance to agriculture, and because of
      their relative structural and biochemical simplicity. Excellent genomic resources
      have been established for the study of Arabidopsis roots, however, a
      comprehensive microarray analysis of the root transcriptome following NaCl
      exposure is required to further understand plant responses to abiotic stress and
      facilitate future, systems-based analyses of the underlying regulatory networks.
      RESULTS: We used microarrays of 70-mer oligonucleotide probes representing 23,686
      Arabidopsis genes to identify root transcripts that changed in relative abundance
      following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment
      analysis identified groups of structurally or functionally related genes whose
      members were statistically over-represented among up- or down-regulated
      transcripts. Our results are consistent with generally observed stress response
      themes, and highlight potentially important roles for underappreciated gene
      families, including: several groups of transporters (e.g. MATE, LeOPT1-like);
      signalling molecules (e.g. PERK kinases, MLO-like receptors), carbohydrate active
      enzymes (e.g. XTH18), transcription factors (e.g. members of ZIM, WRKY, NAC), and
      other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1). We verified the NaCl
      inducible expression of selected transcription factors and other genes by qRT
      PCR. CONCLUSION: Microarray profiling of NaCl-treated Arabidopsis roots revealed
      dynamic changes in transcript abundance for at least 20% of the genome, including
      hundreds of transcription factors, kinases/phosphatases, hormone-related genes,
      and effectors of homeostasis, all of which highlight the complexity of this
      stress response. Our identification of these transcriptional responses, and
      groups of evolutionarily related genes with either similar or divergent
      transcriptional responses to stress, will facilitate mapping of regulatory
      networks and extend our ability to improve salt tolerance in plants.

PMID- 17038191
TI  - MIMOX: a web tool for phage display based epitope mapping.
AB  - BACKGROUND: Phage display is widely used in basic research such as the
      exploration of protein-protein interaction sites and networks, and applied
      research such as the development of new drugs, vaccines, and diagnostics. It has
      also become a promising method for epitope mapping. Research on new algorithms
      that assist and automate phage display based epitope mapping has attracted many
      groups. Most of the existing tools have not been implemented as an online service
      until now however, making it less convenient for the community to access,
      utilize, and evaluate them. RESULTS: We present MIMOX, a free web tool that helps
      to map the native epitope of an antibody based on one or more user supplied
      mimotopes and the antigen structure. MIMOX was coded in Perl using modules from
      the Bioperl project. It has two sections. In the first section, MIMOX provides a
      simple interface for ClustalW to align a set of mimotopes. It also provides a
      simple statistical method to derive the consensus sequence and embeds JalView as
      a Java applet to view and manage the alignment. In the second section, MIMOX can
      map a single mimotope or a consensus sequence of a set of mimotopes, on to the
      corresponding antigen structure and search for all of the clusters of residues
      that could represent the native epitope. NACCESS is used to evaluate the surface
      accessibility of the candidate clusters; and Jmol is embedded to view them
      interactively in their 3D context. Initial case studies show that MIMOX can
      reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as
      providing novel, rational results. CONCLUSION: A web-based tool called MIMOX has
      been developed for phage display based epitope mapping. As a publicly available
      online service in this area, it is convenient for the community to access,
      utilize, and evaluate, complementing other existing programs. MIMOX is freely
      available at http://web.kuicr.kyoto-u.ac.jp/~hjian/mimox.

PMID- 17038192
TI  - Application of Poisson kriging to the mapping of cholera and dysentery incidence
      in an endemic area of Bangladesh.
AB  - BACKGROUND: Disease maps can serve to display incidence rates geographically, to
      inform on public health provision about the success or failure of interventions,
      and to make hypothesis or to provide evidences concerning disease etiology.
      Poisson kriging was recently introduced to filter the noise attached to rates
      recorded over sparsely populated administrative units. Its benefit over simple
      population-weighted averages and empirical Bayesian smoothers was demonstrated by
      simulation studies using county-level cancer mortality rates. This paper presents
      the first application of Poisson kriging to the spatial interpolation of local
      disease rates, resulting in continuous maps of disease rate estimates and the
      associated prediction variance. The methodology is illustrated using cholera and
      dysentery data collected in a cholera endemic area (Matlab) of Bangladesh.
      RESULTS: The spatial analysis was confined to patrilineally-related clusters of
      households, known as baris, located within 9 kilometers from the Matlab hospital
      to avoid underestimating the risk of disease incidence, since patients far away
      from the medical facilities are less likely to travel. Semivariogram models
      reveal a range of autocorrelation of 1.1 km for dysentery and 0.37 km for
      cholera. This result translates into a cholera risk map that is patchier than the
      dysentery map that shows a large zone of high incidence in the south-central part
      of the study area, which is quasi-urban. On both maps, lower risk values are
      found in the Northern part of the study area, which is also the most distant from
      the Matlab hospital. The weaker spatial continuity of cholera versus dysentery
      incidence rates resulted in larger kriging variance across the study area.
      CONCLUSION: The approach presented in this paper enables researchers to
      incorporate the pattern of spatial dependence of incidence rates into the mapping
      of risk values and the quantification of the associated uncertainty. Differences
      in spatial patterns, in particular the range of spatial autocorrelation, reflect
      differences in the mode of transmission of cholera and dysentery. Our risk maps
      for cholera and dysentery incidences should help identifying putative factors of
      increased disease incidence, leading to more effective prevention and remedial
      actions in endemic areas.

PMID- 17038193
TI  - A Fisheye Viewer for microarray-based gene expression data.
AB  - BACKGROUND: Microarray has been widely used to measure the relative amounts of
      every mRNA transcript from the genome in a single scan. Biologists have been
      accustomed to reading their experimental data directly from tables. However,
      microarray data are quite large and are stored in a series of files in a machine
      readable format, so direct reading of the full data set is not feasible. The
      challenge is to design a user interface that allows biologists to usefully view
      large tables of raw microarray-based gene expression data. This paper presents
      one such interface--an electronic table (E-table) that uses fisheye distortion
      technology. RESULTS: The Fisheye Viewer for microarray-based gene expression data
      has been successfully developed to view MIAME data stored in the MAGE-ML format.
      The viewer can be downloaded from the project web site
      http://polaris.imt.uwm.edu:7777/fisheye/. The fisheye viewer was implemented in
      Java so that it could run on multiple platforms. We implemented the E-table by
      adapting JTable, a default table implementation in the Java Swing user interface
      library. Fisheye views use variable magnification to balance magnification for
      easy viewing and compression for maximizing the amount of data on the screen.
      CONCLUSION: This Fisheye Viewer is a lightweight but useful tool for biologists
      to quickly overview the raw microarray-based gene expression data in an E-table.

PMID- 17038194
TI  - Global response to pandemic flu: more research needed on a critical front.
AB  - If and when sustained human-to-human transmission of H5N1 becomes a reality, the
      world will no longer be dealing with sporadic avian flu borne along migratory
      flight paths of birds, but aviation flu - winged at subsonic speed along
      commercial air conduits to every corner of planet Earth. Given that air
      transportation is the one feature that most differentiates present day
      transmission scenarios from those in 1918, our present inability to prevent
      spread of influenza by international air travel, as reckoned by the World Health
      Organization, constitutes a major weakness in the current global preparedness
      plan against pandemic flu. Despite the lessons of SARS, it is surprising that
      aviation-related health policy options have not been more rigorously evaluated,
      or scientific research aimed at strengthening public health measures on the air
      transportation front, more energetically pursued.

PMID- 17038195
TI  - Expoldb: expression linked polymorphism database with inbuilt tools for analysis
      of expression and simple repeats.
AB  - BACKGROUND: Quantitative variation in gene expression has been proposed to
      underlie phenotypic variation among human individuals. A facilitating step
      towards understanding the basis for gene expression variability is associating
      genome wide transcription patterns with potential cis modifiers of gene
      expression. DESCRIPTION: EXPOLDB, a novel Database, is a new effort addressing
      this need by providing information on gene expression levels variability across
      individuals, as well as the presence and features of potentially polymorphic
      (TG/CA)n repeats. EXPOLDB thus enables associating transcription levels with the
      presence and length of (TG/CA)n repeats. One of the unique features of this
      database is the display of expression data for 5 pairs of monozygotic twins,
      which allows identification of genes whose variability in expression, are
      influenced by non-genetic factors including environment. In addition to queries
      by gene name, EXPOLDB allows for queries by a pathway name. Users can also upload
      their list of HGNC (HUGO (The Human Genome Organisation) Gene Nomenclature
      Committee) symbols for interrogating expression patterns. The online application
      'SimRep' can be used to find simple repeats in a given nucleotide sequence. To
      help illustrate primary applications, case examples of Housekeeping genes and the
      RUNX gene family, as well as one example of glycolytic pathway genes are
      provided. CONCLUSION: The uniqueness of EXPOLDB is in facilitating the
      association of genome wide transcription variations with the presence and type of
      polymorphic repeats while offering the feature for identifying genes whose
      expression variability are influenced by non genetic factors including
      environment. In addition, the database allows comprehensive querying including
      functional information on biochemical pathways of the human genes. EXPOLDB can be
      accessed at http://expoldb.igib.res.in/expol.

PMID- 17038196
TI  - Microbicides 2006 conference.
AB  - Current HIV/AIDS statistics show that women account for almost 60% of HIV
      infections in Sub-Saharan Africa. HIV prevention tools such as male and female
      condoms, abstinence and monogamy are not always feasible options for women due to
      various socio-economic and cultural factors. Microbicides are products designed
      to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition.
      The biannual Microbicides conference took place in Cape Town, South Africa from
      23-26 April 2006. The conference was held for the first time on the African
      continent, the region worst affected by the HIV/AIDS pandemic. The conference
      brought together a record number of 1,300 scientists, researchers, policy makers,
      healthcare workers, communities and advocates. The conference provided an
      opportunity for an update on microbicide research and development as well as
      discussions around key issues such as ethics, acceptability, access and community
      involvement. This report discusses the current status of microbicide research and
      development, encompassing basic and clinical science, social and behavioural
      science, and community mobilisation and advocacy activities.

PMID- 17038197
TI  - Development and validation of MIX: comprehensive free software for meta-analysis
      of causal research data.
AB  - BACKGROUND: Meta-analysis has become a well-known method for synthesis of
      quantitative data from previously conducted research in applied health sciences.
      So far, meta-analysis has been particularly useful in evaluating and comparing
      therapies and in assessing causes of disease. Consequently, the number of
      software packages that can perform meta-analysis has increased over the years.
      Unfortunately, it can take a substantial amount of time to get acquainted with
      some of these programs and most contain little or no interactive educational
      material. We set out to create and validate an easy-to-use and comprehensive meta
      analysis package that would be simple enough programming-wise to remain available
      as a free download. We specifically aimed at students and researchers who are new
      to meta-analysis, with important parts of the development oriented towards
      creating internal interactive tutoring tools and designing features that would
      facilitate usage of the software as a companion to existing books on meta
      analysis. RESULTS: We took an unconventional approach and created a program that
      uses Excel as a calculation and programming platform. The main programming
      language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for
      Applications in Excel 2000 and higher. The development took approximately two
      years and resulted in the 'MIX' program, which can be downloaded from the
      program's website free of charge. Next, we set out to validate the MIX output
      with two major software packages as reference standards, namely STATA (metan,
      metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta
      analyses that had been published in major journals were used as data sources. All
      numerical and graphical results from analyses with MIX were identical to their
      counterparts in STATA and CMA. The MIX program distinguishes itself from most
      other programs by the extensive graphical output, the click-and-go (Excel)
      interface, and the educational features. CONCLUSION: The MIX program is a valid
      tool for performing meta-analysis and may be particularly useful in educational
      environments. It can be downloaded free of charge via http://www.mix-for-meta
      analysis.info or http://sourceforge.net/projects/meta-analysis.

PMID- 17038198
TI  - TasA-tasB, a new putative toxin-antitoxin (TA) system from Bacillus thuringiensis
      pGI1 plasmid is a widely distributed composite mazE-doc TA system.
AB  - BACKGROUND: Post-segregational killing systems are present in a large variety of
      microorganisms. When found on plasmids, they are described as addiction systems
      that act to maintain the plasmid during the partitioning of the cell. The plasmid
      to be maintained through the generations harbours a group of two genes, one
      coding for a stable toxin and the other coding for an unstable antitoxin that
      inhibits the effects of the toxin. If, during cell division, the plasmid is lost,
      the toxin and antitoxin proteins present in the cytosol cease to be newly
      expressed. The level of unstable antitoxin protein then rapidly decreases,
      leaving the toxin free to act on the cellular target, leading to cell death.
      Consequently, only cells harbouring the plasmid can survive. RESULTS: The pGI1
      plasmid of Bacillus thuringiensis H1.1 harbours a group of two genes, one showing
      similarities with the Doc toxin of the phd-doc toxin-antitoxin system,
      potentially coding for a toxin-antitoxin system. Attempts were made to clone this
      putative system in the Gram-negative host Escherichia coli. The putative
      antitoxin tasA was easily cloned in E. coli. However, although several
      combinations of DNA fragment were used in the cloning strategy, only clones
      containing a mutation in the toxin gene could be recovered, suggesting a toxic
      activity of TasB. An exhaustive search was carried out in order to index genes
      homologous to those of the putative tasA-tasB system among microorganisms. This
      study revealed the presence of this system in great number and in a large variety
      of microorganisms, either as tasA-tasB homologues or in association with toxins
      (or antitoxins) from other TA systems. CONCLUSION: In this work, we showed that
      the pGI1 plasmid of B. thuringiensis H1.1 harbours genes resembling a toxin
      antitoxin system, named tasA-tasB for thuringiensis addiction system. This system
      appeared to be functional but unregulated in E. coli. Bioinformatics studies
      showed that the tasAB system is present on plasmids or chromosomes of a large
      variety of microorganisms. Moreover, the association between TasA antitoxin with
      toxins other than TasB (and vice versa) revealed the composite and modular nature
      of bacterial TA systems.

PMID- 17038199
TI  - Diagnostic value and prognostic implications of serum procalcitonin after cardiac
      surgery: a systematic review of the literature.
AB  - INTRODUCTION: Systemic inflammatory response syndrome is common after surgery,
      and it can be difficult to discriminate between infection and inflammation. We
      performed a review of the literature with the aims of describing the evolution of
      serum procalcitonin (PCT) levels after uncomplicated cardiac surgery,
      characterising the role of PCT as a tool in discriminating infection, identifying
      the relation between PCT, organ failure, and severity of sepsis syndromes, and
      assessing the possible role of PCT in detection of postoperative complications
      and mortality. METHODS: We performed a search on MEDLINE using the keyword
      'procalcitonin' crossed with 'cardiac surgery,' 'heart,' 'postoperative,' and
      'transplantation.' Our search was limited to human studies published between
      January 1990 and June 2006. RESULTS: Uncomplicated cardiac surgery induces a
      postoperative increase in serum PCT levels. Peak PCT levels are reached within 24
      hours postoperatively and return to normal levels within the first week. This
      increase seems to be dependent on the surgical procedure and on intraoperative
      events. Although PCT values reported in infected patients are generally higher
      than in non-infected patients after cardiac surgery, the cutoff point for
      discriminating infection ranges from 1 to 5 ng/ml, and the dynamics of PCT levels
      over time may be more important than absolute values. PCT is superior to C
      reactive protein in discriminating infections in this setting. PCT levels are
      higher with increased severity of sepsis and the presence of organ
      dysfunction/failure and in patients with a poor outcome or in those who develop
      postoperative complications. PCT levels typically remain unchanged after acute
      rejection but increase markedly after bacterial and fungal infections. Systemic
      infections are associated with greater PCT elevation than is local infection.
      Viral infections are difficult to identify based on PCT measurements. CONCLUSION:
      The dynamics of PCT levels, rather than absolute values, could be important in
      identifying patients with infectious complications after cardiac surgery. PCT is
      useful in differentiating acute graft rejection after heart and/or lung
      transplantation from bacterial and fungal infections. Further studies are needed
      to define cutoff points and to incorporate PCT levels in useful prediction
      models.

PMID- 17038200
TI  - Psychometric evaluation of a short measure of social capital at work.
AB  - BACKGROUND: Prior studies on social capital and health have assessed social
      capital in residential neighbourhoods and communities, but the question whether
      the concept should also be applicable in workplaces has been raised. The present
      study reports on the psychometric properties of an 8-item measure of social
      capital at work. METHODS: Data were derived from the Finnish Public Sector Study
      (N = 48,592) collected in 2000-2002. Based on face validity, an expert unfamiliar
      with the data selected 8 questionnaire items from the available items for a scale
      of social capital. Reliability analysis included tests of internal consistency,
      item-total correlations, and within-unit (interrater) agreement by rwg index. The
      associations with theoretically related and unrelated constructs were examined to
      assess convergent and divergent validity (construct validity). Criterion-related
      validity was explored with respect to self-rated health using multilevel logistic
      regression models. The effects of individual level and work unit level social
      capital were modelled on self-rated health. RESULTS: The internal consistency of
      the scale was good (Cronbach's alpha = 0.88). The rwg index was 0.88, which
      indicates a significant within-unit agreement. The scale was associated with, but
      not redundant to, conceptually close constructs such as procedural justice, job
      control, and effort-reward imbalance. Its associations with conceptually more
      distant concepts, such as trait anxiety and magnitude of change in work, were
      weaker. In multilevel models, significantly elevated age adjusted odds ratios
      (ORs) of poor self-rated health (OR = 2.42, 95% confidence interval (CI): 2.24
      2.61 for the women and OR = 2.99, 95% CI: 2.56-3.50 for the men) were observed
      for the employees in the lowest vs. highest quartile of individual level social
      capital. In addition, low social capital at the work unit level was associated
      with a higher likelihood of poor self-rated health. CONCLUSION: Psychometric
      techniques show our 8-item measure of social capital to be a valid tool
      reflecting the construct and displaying the postulated links with other
      variables.

PMID- 17038201
TI  - Development, structure, and function of a novel respiratory organ, the lung-air
      sac system of birds: to go where no other vertebrate has gone.
AB  - Among the air-breathing vertebrates, the avian respiratory apparatus, the lung
      air sac system, is the most structurally complex and functionally efficient.
      After intricate morphogenesis, elaborate pulmonary vascular and airway
      (bronchial) architectures are formed. The crosscurrent, countercurrent, and
      multicapillary serial arterialization systems represent outstanding operational
      designs. The arrangement between the conduits of air and blood allows the
      respiratory media to be transported optimally in adequate measures and rates and
      to be exposed to each other over an extensive respiratory surface while separated
      by an extremely thin blood-gas barrier. As a consequence, the diffusing capacity
      (conductance) of the avian lung for oxygen is remarkably efficient. The foremost
      adaptive refinements are: (1) rigidity of the lung which allows intense
      subdivision of the exchange tissue (parenchyma) leading to formation of very
      small terminal respiratory units and consequently a vast respiratory surface; (2)
      a thin blood-gas barrier enabled by confinement of the pneumocytes (especially
      the type II cells) and the connective tissue elements to the atria and
      infundibulae, i.e. away from the respiratory surface of the air capillaries; (3)
      physical separation (uncoupling) of the lung (the gas exchanger) from the air
      sacs (the mechanical ventilators), permitting continuous and unidirectional
      ventilation of the lung. Among others, these features have created an incredibly
      efficient gas exchanger that supports the highly aerobic lifestyles and great
      metabolic capacities characteristic of birds. Interestingly, despite remarkable
      morphological heterogeneity in the gas exchangers of extant vertebrates at
      maturity, the processes involved in their formation and development are very
      similar. Transformation of one lung type to another is clearly conceivable,
      especially at lower levels of specialization. The crocodilian (reptilian)
      multicameral lung type represents a Bauplan from which the respiratory organs of
      nonavian theropod dinosaurs and the lung-air sac system of birds appear to have
      evolved. However, many fundamental aspects of the evolution, development, and
      even the structure and function of the avian respiratory system still remain
      uncertain.

PMID- 17038202
TI  - Orchestration of avian reproductive effort: an integration of the ultimate and
      proximate bases for flexibility in clutch size, incubation behaviour, and yolk
      androgen deposition.
AB  - How much effort to expend in any one bout of reproduction is among the most
      important decisions made by an individual that breeds more than once. According
      to life-history theory, reproduction is costly, and individuals that invest too
      much in a given reproductive bout pay with reduced reproductive output in the
      future. Likewise, investing too little does not maximize reproductive potential.
      Because reproductive effort relative to output can vary with predictable and
      unpredictable challenges and opportunities, no single level of reproductive
      effort maximizes fitness. This leads to the prediction that individuals
      possessing behavioural mechanisms to buffer challenges and take advantage of
      opportunities would incur fitness benefits. Here, we review evidence in birds,
      primarily of altricial species, for the presence of at least two such mechanisms
      and evidence for and against the seasonal coordination of these mechanisms
      through seasonal changes in plasma concentrations of the pituitary hormone
      prolactin. First, the seasonal decline in clutch size of most bird species may
      partially offset a predictable seasonal decline in the reproductive value of
      offspring. Second, establishing a developmental sibling-hierarchy among offspring
      may hedge against unpredictable changes in resource availability and offspring
      viability or quality, and minimize energy expenditure in raising a brood. The
      hierarchy may be a product, in part, of the timing of incubation onset relative
      to clutch completion and the rate of yolk androgen deposition during the laying
      cycle. Because clutch size should influence the effects of both these traits on
      the developmental hierarchy, we predicted and describe evidence in some species
      that females adjust the timing of incubation onset and rate of yolk androgen
      deposition to match clutch size. Studies on domesticated precocial species reveal
      an inhibitory effect of the pituitary hormone prolactin on egg laying, suggesting
      a possible hormonal basis for the regulation of clutch size. Studies on the
      American kestrel (Falco sparverius) and other species suggest that the seasonal
      increase in plasma concentrations of prolactin may regulate both a seasonal
      advance in the timing of incubation onset and a seasonal increase in the rate of
      yolk androgen deposition. These observations, together with strong conceptual
      arguments published previously, raise the possibility that a single hormone,
      prolactin, functions as the basis of a common mechanism for the seasonal
      adjustment of reproductive effort. However, a role for prolactin in regulating
      clutch size in any species is not firmly established, and evidence from some
      species indicates that clutch size may not be coupled to the timing of incubation
      onset and rate of yolk androgen deposition. A dissociation between the regulation
      of clutch size and the regulation of incubation onset and yolk androgen
      deposition may enable an independent response to the predictable and
      unpredictable challenges and opportunities faced during reproduction.

PMID- 17038203
TI  - Antimicrobial resistance in non-typhoidal salmonellas from humans in Northern
      Ireland, 2001-2003: standardization needed for better epidemiological monitoring.
AB  - This study investigated the identification and antimicrobial susceptibility
      testing of Salmonella isolates in Northern Ireland during 2001-2003. All six
      participating hospital laboratories used similar methods. Identification and
      antimicrobial resistance of human enteric (n=897) Salmonella isolates were
      analysed by retrospective collation of laboratory records. Resistance of human
      Salmonella isolates to nalidixic acid was 16% but resistance to ciprofloxacin or
      cefotaxime was rare (<1%). Minor inter-laboratory variations in sensitivity
      testing practices make it difficult to compare antimicrobial sensitivity results
      reliably and also to monitor for epidemic clones such as S. Typhimurium DT104
      with the ACSSuT resistance pattern. The outcome of this study was the adoption of
      a standardized regional approach to the isolation of salmonella antimicrobial
      resistance. This should improve epidemiological monitoring of epidemic clones and
      assure optimum treatment options are available. In cases of treatment failure,
      MICs to third-generation cephalosporins and ciprofloxacin should be determined.

PMID- 17038204
TI  - Greek measles epidemic strain, 2005-2006.
AB  - The purpose of this work was the molecular study of the virus strain that caused
      the last measles outbreak in Greece. Twenty-four saliva specimens were obtained
      from selected patients serologically confirmed as measles cases between December
      2005 and March 2006. Measles virus (MV) detection was performed by a nested RT
      PCR. The 447-bp segment of the N gene of these MV strains was used for
      genotyping. The N gene sequences of the Greek MV strains were identical to each
      other, therefore a phylogenetic tree was constructed using one representative MV
      (ThesGRE/06). Our data show that the MV strain which caused the 2005-2006
      outbreak in Greece belongs to genotype D6, and differs by 0.68% from the New
      Jersey D6 strain and by 5.5% from the MV vaccine strain Edmonston B (U03656)
      belonging to genotype A.

PMID- 17038205
TI  - Sex differences in brain activation patterns during processing of positively and
      negatively valenced emotional words.
AB  - BACKGROUND: Previous studies have suggested that men and women process emotional
      stimuli differently. In this study, we used event-related functional magnetic
      resonance imaging (fMRI) to investigate gender differences in regional cerebral
      activity during the perception of positive or negative emotions. METHOD: The
      experiment comprised two emotional conditions (positively/negatively valenced
      words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy
      volunteers (19 males, 19 females) were investigated. A direct comparison of brain
      activation between men and women revealed differential activation in the right
      putamen, the right superior temporal gyrus, and the left supramarginal gyrus
      during processing of positively valenced words versus non-words for women versus
      men. By contrast, during processing of negatively valenced words versus non
      words, relatively greater activation was seen in the left perirhinal cortex and
      hippocampus for women versus men, and in the right supramarginal gyrus for men
      versus women. CONCLUSIONS: Our findings suggest gender-related neural responses
      to emotional stimuli and could contribute to the understanding of mechanisms
      underlying the gender disparity of neuropsychiatric diseases such as mood
      disorders.

PMID- 17038206
TI  - Ovarian hormones and binge eating in bulimia nervosa.
AB  - BACKGROUND: Symptom fluctuation in bulimia nervosa (BN) is related to menstrual
      cycle phase. However, the relationship between bulimic symptoms and ovarian
      hormones (estrogens and progesterone) has not been examined directly in women
      with BN. METHOD: Regularly menstruating women with DSM-IV BN (n=9) and regularly
      menstruating controls (n=8) collected hormone samples and recorded mood and
      bulimic symptoms daily for 35 consecutive days. Estradiol and progesterone were
      measured by radioimmunoassay. Within-subject analyses examined prospective
      longitudinal associations between changes in ovarian hormones and changes in
      binge frequency in women with BN. Analyses controlled for the possible influence
      of negative affect on binge frequency as well as the influence of progesterone
      when examining estradiol associations and the influence of estradiol when
      examining progesterone associations. Between-subject analyses examined whether
      women with BN were more likely to have disrupted hormonal profiles than controls.
      RESULTS: Increases in binge eating were significantly associated with both
      decreases in estradiol and increases in progesterone in BN women with intact
      menstrual cycles. Although BN women were more likely to have disrupted hormone
      profiles than controls, this difference did not reach statistical significance,
      and mean estradiol and progesterone levels did not differ between bulimic and
      control groups. CONCLUSIONS: The results are consistent with those from
      experimental animal studies and suggest that decreases in estradiol and increases
      in progesterone may contribute to increases in binge eating. Ovarian hormone
      function represents a promising candidate for unraveling the neurobiological
      mechanisms of binge eating.

PMID- 17038207
TI  - DSM-IV alcohol dependence: a categorical or dimensional phenotype?
AB  - BACKGROUND: Etiologic research on complex disorders including alcohol dependence
      requires informative phenotypes. Information is lost when categorical variables
      represent inherently dimensional conditions. We investigated the validity of DSM
      IV alcohol dependence as a dimensional phenotype by examining evidence for
      linearity and thresholds in associations with validating variables. METHOD:
      Current drinkers in the National Longitudinal Alcohol Epidemiologic Survey
      (NLAES) (n=18352) and National Epidemiologic Survey of Alcohol and Related
      Conditions (NESARC) (n=20836) were analyzed. Validating variables included family
      alcoholism, early-onset drinking, and alcohol treatment. Logistic or Poisson
      regression modeled the relationships between the validating variables and
      dependence in categorical, dimensional or hybrid forms, with severity defined as
      number of current DSM-IV alcohol-dependence criteria. Wald tests assessed
      differences between models. RESULTS: No evidence was found for boundaries between
      categories. Instead, the association of alcohol dependence with the validating
      variables generally increased in linear fashion as the number of alcohol
      dependence criteria increased. For NLAES models of family alcoholism, early-onset
      drinking and treatment, the lines had zero intercepts, with slopes of 0.18, 0.27,
      0.70, respectively. For NESARC models of family history and early-onset drinking,
      the zero intercept lines had slopes of 0.20, 0.33, and 0.77, respectively. Wald
      tests indicated that models representing alcohol dependence as a dimensional
      linear predictor best described the association between dependence criteria and
      the validating variables. CONCLUSIONS: The sample sizes allowed strong tests.
      Diagnoses are necessary for clinical decision-making, but a dimensional alcohol
      dependence indicator should provide more information for research purposes.

PMID- 17038208
TI  - Lifetime prevalence and inter-cohort variation in DSM-IV disorders in
      metropolitan China.
AB  - BACKGROUND: This is the first study to examine variation across cohorts in
      lifetime risk of DSM-IV mental disorders in metropolitan China. METHOD: Face-to
      face household interviews of 2633 adults in Beijing and 2568 adults in Shanghai
      were conducted from November 2001 to February 2002 using a multi-stage household
      probability sampling method. The Chinese World Mental Health (WMH) Survey
      Initiative version of the WHO Composite International Diagnostic Interview (WMH
      CIDI) was used for assessment. RESULTS: Lifetime prevalence of any disorder was
      13.2%. Alcohol abuse (4.7%), major depressive disorder (3.5%), and specific
      phobia (2.6%) were the most common disorders. The median age of onset was later
      for mood (43 years) than anxiety (17 years) and substance use (25 years)
      disorders. Compared to observed lifetime prevalence, the projected lifetime risk
      as of age 75 years increased by 106% for major depressive disorder (7.2%), and
      was uniformly higher for all disorders. Relative odds of any lifetime disorder
      were 4.7 in the most recent cohorts (ages 18-34) compared to the eldest cohorts
      (ages > or =65). CONCLUSIONS: The findings of this cross-sectional study tally
      with the view that rapid socioeconomic changes may bring about increasing
      incidence of mental disorders in China. However, prospective longitudinal studies
      are needed to confirm if the increase is real. Because of the huge size of the
      Chinese population, any increase in projected lifetime risk of mental disorders
      represents an enormous increase in the number of affected individuals.

PMID- 17038209
TI  - Restraint stress influences AP-1 and CREB DNA-binding activity induced by chronic
      lithium treatment in the rat frontal cortex and hippocampus.
AB  - The therapeutic efficacy of mood stabilizers may involve the regulation of gene
      expression mediated by transcription factor activation. In this study, we
      investigated AP-1 and cAMP response element-binding protein (CREB) DNA-binding
      activity in the rat frontal cortex and hippocampus of rats fed a control diet, a
      lithium diet for 7 wk, or 6 wk of lithium, followed by withdrawal for 7 d.
      Subsequently, animals were exposed to restraint stress or no stress and the DNA
      binding activities assessed at 2, 8 and 24 h post-stress. AP-1 activity was
      increased in both brain regions by lithium, an effect that persisted with lithium
      discontinuation. Restraint stress induced AP-1 activity in the frontal cortex of
      the control group. This stress-induced effect on AP-1 activity was attenuated in
      lithium-treated and lithium-withdrawn animals. AP-1 DNA binding was also induced
      by stress in the hippocampus of control animals and the activity diminished over
      time in the lithium and lithium-withdrawn groups. CREB activity also increased in
      the frontal cortex and hippocampus of the lithium-treated group. Stress increased
      CREB activity in the frontal cortex of the controls, and was slightly attenuated
      with lithium treatment. CREB activity in the hippocampus was insensitive to
      stress. The proteins involved in the AP-1 and CREB transcription complexes were
      also characterized. Our findings of increased AP-1 and CREB binding after lithium
      are consistent with lithium's inhibitory effect on glycogen synthase kinase
      3beta, which has been show to negatively regulate AP-1 and CREB transcriptional
      activity.

PMID- 17038210
TI  - The architecture and function of the light-harvesting apparatus of purple
      bacteria: from single molecules to in vivo membranes.
AB  - This review describes the structures of the two major integral membrane pigment
      complexes, the RC-LH1 'core' and LH2 complexes, which together make up the light
      harvesting system present in typical purple photosynthetic bacteria. The antenna
      complexes serve to absorb incident solar radiation and to transfer it to the
      reaction centres, where it is used to 'power' the photosynthetic redox reaction
      and ultimately leads to the synthesis of ATP. Our current understanding of the
      biosynthesis and assembly of the LH and RC complexes is described, with special
      emphasis on the roles of the newly described bacteriophytochromes. Using both the
      structural information and that obtained from a wide variety of biophysical
      techniques, the details of each of the different energy-transfer reactions that
      occur, between the absorption of a photon and the charge separation in the RC,
      are described. Special emphasis is given to show how the use of single-molecule
      spectroscopy has provided a more detailed understanding of the molecular
      mechanisms involved in the energy-transfer processes. We have tried, with the
      help of an Appendix, to make the details of the quantum mechanics that are
      required to appreciate these molecular mechanisms, accessible to mathematically
      illiterate biologists. The elegance of the purple bacterial light-harvesting
      system lies in the way in which it has cleverly exploited quantum mechanics.

PMID- 17038211
TI  - Opioid-induced hyperalgesia.

PMID- 17038212
TI  - Concentration of levobupivacaine solutions is labelled differently than that of
      other local anaesthetic solutions.

PMID- 17038213
TI  - Downbeat nystagmus as a manifestation of intrathecal morphine toxicity.

PMID- 17038214
TI  - The effect of dexamethasone on recovery from cleft palate surgery.

PMID- 17038215
TI  - Severe myalgia associated with propofol sedation.

PMID- 17038216
TI  - Paediatric renal transplantation: a single centre study.

PMID- 17038217
TI  - Tension pneumocephalus following deep brain stimulation surgery with bispectral
      index monitoring.

PMID- 17038218
TI  - Ketamine-induced emergence reactions after desflurane anaesthesia.

PMID- 17038219
TI  - With bleomycin, that's too much oxygen.

PMID- 17038220
TI  - Mitral valve surgery and acute renal failure.

PMID- 17038225
TI  - Anaesthetists inability to assess depth of anaesthesia:why not use the IFT?

PMID- 17038226
TI  - Value of BIS-monitoring for electroconvulsive therapy.

PMID- 17038227
TI  - Sedation in dentistry: current sedation practice in Italy.

PMID- 17038228
TI  - Should we aspirate middle-ear effusions prior to insertion of ventilation tubes?
AB  - BACKGROUND: Routine aspiration of middle-ear effusions prior to ventilation tube
      (grommet) insertion is practised by many surgeons. It has been suggested that
      removing the fluid from the middle ear improves immediate post-operative hearing
      levels and reduces the chance of the ventilation tube becoming obstructed. The
      potential adverse effects of applying suction to the middle ear include acoustic
      trauma and an increased risk of tympanosclerosis and otorrhoea. We undertook a
      review of the literature in order to determine the benefits or side effects
      associated with middle-ear aspiration prior to ventilation tube insertion.
      OBJECTIVES: To compare clinical outcomes associated with aspirating versus not
      aspirating the middle ear prior to ventilation tube insertion. METHODS: The
      Cochrane ENT group trials register, DARE, the Cochrane central register of
      controlled trials (CENTRAL), MEDLINE (1960-2005) and EMBASE (1960-2005) were
      searched using relevant terms. Reference lists of selected studies were scanned
      for additional research material. RESULTS: Seven studies were identified, of
      which three fitted the inclusion criteria of our review. Current evidence
      suggests that aspiration of middle-ear effusions prior to insertion of
      ventilation tubes is not associated with any improvement in clinical outcome, in
      terms of post-operative hearing levels, otorrhoea or rates of blockage of
      ventilation tubes. Significantly increased rates of tympanosclerosis were
      observed in one study and the development of acoustic trauma was observed;
      however, no significant association was confirmed. Although more research is
      needed, there is no evidence that aspiration of middle-ear effusion prior to
      grommet insertion confers any advantage.

PMID- 17038229
TI  - Posterior canal wall reconstruction with a composite cartilage titanium mesh
      graft in canal wall down tympanoplasty and revision surgery for radical cavities.
AB  - OBJECTIVES: To investigate posterior external ear canal wall reconstruction with
      a composite cartilage titanium mesh graft in canal wall down tympanoplasty and
      revision surgery for open mastoids. STUDY DESIGN: Retrospective case review.
      SETTING: Tertiary referral centre. METHODS: As a preliminary study, 15 selected
      patients underwent reconstruction of a posterior ear canal wall defect with
      titanium mesh. Large defects of the posterior external auditory canal wall,
      resulting from canal wall down tympanoplasty or present in revision surgery, were
      eliminated by reconstruction using a titanium mesh. The mesh was covered with
      conchal cartilage and attached to the cortical mastoid bone using 3-mm titanium
      screws. RESULTS: All patients maintained a normal contour of the external ear
      canal, without depression, extrusion or infection. There were no failures, based
      on short-term post-operative controls. However, two procedures had to be revised
      due to incomplete coverage of the titanium mesh. CONCLUSIONS: This study shows
      that reconstruction of the posterior ear canal wall with a composite cartilage
      titanium mesh is a valuable method for preserving the morphology of the external
      auditory canal in selected cases. Problems occurring in canal wall down
      tympanomastoidectomy and radical cavities may therefore be avoided. However, long
      term results have yet to be evaluated.

PMID- 17038230
TI  - Management of clinically diagnosed subacute rhinosinusitis in children under the
      age of two years: a randomized, controlled study.
AB  - BACKGROUND: In children, a diagnosis of rhinosinusitis is usually made on
      clinical grounds. Subacute rhinosinusitis (SRS) may be the cause of persistent
      cough, low-grade fever, snoring, ear problems and difficult feeding in children
      under the age of two years. OBJECTIVE: To compare the efficacy of culture-based
      antibiotics and empiric amoxicillin-clavulanate (40 mg/kg/day) in treating SRS in
      children under the age of two years. STUDY DESIGN: Randomized, controlled study.
      POPULATION: Sixty children with persistent nasal discharge and nasal obstruction
      (and other related symptoms) for 30-90 days. METHODS: Group one (n = 30) received
      culture-based antibiotics and group two (n = 30) were treated empirically with 40
      mg/kg/day of amoxicillin-clavulanate. Treatment was continued for two weeks.
      RESULTS: At the end of the three-week follow-up period, statistically significant
      greater improvements in nasal obstruction (p = 0.037) and nasal discharge (p =
      0.003) were seen in group one compared with group two. CONCLUSION: culture-based
      antibiotics were more efficacious than empiric amoxicillin-clavulanate (40
      mg/kg/day) in treating SRS in children under the age of two years.

PMID- 17038231
TI  - Validation of sonotubometry in healthy adults.
AB  - BACKGROUND: Frequent active opening of the eustachian tube (ET) allows
      ventilation of the middle ear and equilibration of pressure changes. Active
      opening is accomplished by the contraction of the paratubal muscles during
      swallowing. Because a disturbance of the ventilatory function of the ET may
      contribute to the development of otitis media with effusion, it is important to
      investigate ET function. Sonotubometry can be used to detect whether the ET can
      open or not during swallowing acts. METHODS: We developed a sonotubometer to test
      ET ventilatory function in 36 healthy adults. The width of the test signal
      frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the
      loudness was 95 dB. To test reproducibility, testing took place in two sessions
      of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in
      91.6 per cent of the subjects in at least one of the two measurements. The first
      and the second measurements were highly correlated, with a Spearman's coefficient
      of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET
      function in otologically healthy adults, although, in a few cases, ET opening was
      not registered. Furthermore, we confirmed that our sonometric test equipment had
      acceptable reproducibility. Sonotubometry is a promising method for assessing
      ventilatory ET function. Research is ongoing to test the discriminative power of
      sonotubometry in children with various otological conditions.

PMID- 17038232
TI  - Predictive indicators for thyroid cartilage involvement in carcinoma of the
      larynx seen on spiral computed tomography scans.
AB  - OBJECTIVES: Recent studies have shown that the spiral computed tomography (CT)
      scan is a sensitive imaging modality for predicting neoplastic invasion of
      thyroid cartilage. The objectives of our study were: to assess the accuracy of
      pre-operative spiral CT in predicting thyroid cartilage involvement in patients
      with carcinoma of the larynx; and to elucidate the factors that would accurately
      indicate cartilage involvement. MATERIAL AND METHODS: Medical records, including
      spiral CT scans and pathological reports, were reviewed for 27 patients who had
      undergone laryngectomy in two major hospitals in south Wales. A consultant
      radiologist with special interest in cross-sectional imaging re-evaluated the
      scans to assess neoplastic involvement of the thyroid cartilage, based on
      definite, objective criteria. These criteria included: soft tissue asymmetry;
      loss of medullary space; spiky or irregular surface; distortion of cartilage
      framework; and abnormal soft tissue on both sides of the cartilage. The
      radiological findings were then correlated with the histopathological evidence of
      cartilage invasion by the tumour. RESULTS: Out of the 27 cases, 15 had evidence
      of histological invasion of thyroid cartilage. The most specific criterion to
      predict thyroid cartilage involvement was the presence of tumour on both sides of
      the cartilage (specificity of 91 per cent, sensitivity of 66 per cent). Combining
      two criteria increased both the sensitivity and the specificity to 86 and 91 per
      cent, respectively.

PMID- 17038233
TI  - Endoscopic pituitary adenomectomy.
AB  - The authors' surgical technique for performing pituitary adenomectomy using the
      endoscopic transnasal approach is described.

PMID- 17038234
TI  - Myxofibrosarcoma of the neck.
AB  - We report a rare case of myxofibrosarcoma arising in the neck. A 55-year-old man
      presented with a two-year history of left-sided, painless, submandibular
      swelling. Computed tomography and magnetic resonance imaging (MRI) revealed an 80
      x 35 mm, well defined, lobulated, submandibular tumour extending to the
      parapharyngeal space. The tumour showed uniformly low intensity and marked
      hyperintensity in T1- and T2-weighted MRI scans, respectively, and was scarcely
      enhanced by gadolinium. A tentative diagnosis of lymphangioma or plunging ranula
      was made, and the patient underwent local injection of OK-432, which proved to be
      ineffective. Resection of the tumour was then performed via a transcervical
      approach. The tumour was histopathologically and immunohistochemically diagnosed
      as a low-grade myxofibrosarcoma. The patient's post-operative clinical course was
      uneventful, and the patient was free of disease 27 months after surgery. The
      pathology, clinical characteristics and treatment of myxofibrosarcoma are
      bibliographically reviewed.

PMID- 17038235
TI  - Coexistent acute pyogenic and tubercular petrous apicitis: a diagnostic dilemma.
AB  - We report the case of a 16-year-old boy who presented to us with acute otitis
      media, facial weakness and retro-orbital pain. Computed tomography and magnetic
      resonance imaging (MRI) scans of the head and temporal bone revealed otitis media
      with petrous apicitis. The patient responded to broad-spectrum, parenteral
      antibiotics, with disappearance of facial weakness and reduction in pain. One
      month following the completion of treatment, the patient continued to have dull
      retro-orbital pain and developed ear discharge. A repeat MRI of the temporal bone
      revealed a persistent inflammatory lesion in the petrous apex, with a nodular,
      ring-enhancing lesion in the cerebellum, strongly suggestive of tuberculosis. The
      ear discharge stained positive for acid-fast bacilli and the patient's serum
      enzyme-linked immunosorbent assay for tuberculosis was reactive. The patient
      responded well to anti-tubercular treatment and was disease free eight months
      following the completion of treatment.

PMID- 17038236
TI  - Recombinant protein Bd37 protected gerbils against heterologous challenges with
      isolates of Babesia divergens polymorphic for the bd37 gene.
AB  - The Bd37gene encoding for a glycosyl-phosphatidyl-inositol anchored protein of
      Babesia divergens displays genetic polymorphisms among isolates. Five major
      polymorphic groups (clades) were shown by PCR-RFLP among different B. divergens
      isolates. Each group has been characterized according to a reference Bd37 gene
      (Rouen87, W8843, Y5, 6303E and 1705B). Recombinant (GST fusion) protein (Bd37r)
      expressed from the Bd37 gene, was used as antigen in a saponin-based formulation
      and was able to protect gerbils, after 2 injections at low dose vaccine
      concentration (1 mug per dose), against a virulent challenge with the B.
      divergens Rouen87 isolate. In spite of polymorphism of Bd37 gene, Bd37r induced
      complete immunoprotection against challenges with each of the 5 reference isolate
      groups defined by PCR-RFLP.

PMID- 17038237
TI  - [Critical illness: nutritional support and treatment].

PMID- 17038238
TI  - [Lay emphasis on and advocate strongly nutritional support in clinic].

PMID- 17038239
TI  - [From nutritional support to nutritional treatment--a dialectic evolution].

PMID- 17038241
TI  - [The indication of parenteral nutrition support (draft)].

PMID- 17038240
TI  - [Guidelines of nutritional support in critically ill patients (draft)].

PMID- 17038243
TI  - [Influence of glutamine and growth hormone intensified nutrition support on
      immunomodulation in critically ill elderly patients].
AB  - OBJECTIVE: To evaluate the impacts of glutamine (Gln) and recombinant human
      growth hormone (rhGH) intensified nutrition support on critically ill elderly
      patients. METHODS: Ninety critically ill aged patients were included in a
      prospective, randomized and controlled clinical study, and randomly divided into
      three groups: group A (standard nutrition support), group B (standard nutrition
      support+10% Gln 100 ml/d), group C (standard nutrition support+ Gln 100 ml/d+rhGH
      10 U/d). Before treatment and then 7 and 14 days after treatment, blood samples
      were collected for analysis of serum proteins including albumin (ALB), pre
      albumin (PAB), C-reactive protein (CRP), immunoglobulin G (IgG). Meanwhile, the
      variables including T-cell subsets, CD14 human leukocyte antigen (locus) DR (CD14
      HLA-DR), and total lymphocytes were measured. The changes in acute physiology and
      chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome
      (MODS) scores, the durations of intensive care unit (ICU) stay and mechanical
      ventilation, and 28-day survival rate were recorded. RESULTS: Comparing with
      group A and B, the levels of serum ALB, PAB and IgG were significantly elevated
      in group C. The T-cell subsets, CD14 HLA-DR and the number of total lymphocytes
      were markedly higher in group C (P<0.01), and the APACHE II and MODS scores were
      decreased significantly in group C (P<0.05 or P<0.01). The levels of serum CRP
      were lowered significantly in group C (P<0.01). There were no significant
      differences in the durations of ICU stay, mechanical ventilation and 28-day
      survival rate among three groups (all P>0.05). CONCLUSION: Gln and rhGH
      intensified nutrition support can improve nutritional condition and immune
      function, downregulate the inflammatory response in the critically ill elderly
      patients.

PMID- 17038245
TI  - [Management of nutritional support and stress hyperglycemia after orthotopic
      liver transplantation].
AB  - OBJECTIVE: To study the influence of different nutritional regimes on the stress
      hyperglycemia and the outcome after orthotopic liver transplantation, for the
      purpose of optimizing nutritional regime for early post-operative period.
      METHODS: One hundred and seventy-two patients who received liver transplantation
      for chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) induced hepatic
      function failure or end-stage cirrhosis were enrolled, and the post-operative
      complications and length of stay in intensive care unit (ICU) were
      retrospectively analyzed, in regard to high caloric (HC) or low caloric (LC)
      nutritional regime with their blood glucose controlled to a optimal level.
      RESULTS: After the liver transplantation, those patients who were supplied with
      LC (83.7-104.6 kJ.kg(-1).d(-1)), energized stepwise with higher fat ratio
      (sugar:fat=50%:35%) with blood glucose being maintained <8 mmol/L, had less
      exogenous insulin requirement (P<0.01), lower infection-related mortality rate
      (P<0.05), and shortened weaning from mechanical ventilation time and length of
      stay in ICU (both P<0.05), compared with those who were supplied with HC
      nutrition (125.5-146.4 kJ.kg(-1).d(-1)) with routine sugar and fat ratio
      (55%:35%), and blood glucose maintained at the same level. However, there was no
      significant differences in serum bilirubin contents, incidences of poor healing
      of incision and anastomosis as well as hypoglycemia, and extrinsic albumin
      requirement between two groups. CONCLUSION: LC nutrition regime and controlling
      the blood glucose <8 mmol/L during the early post-operative period may reduce the
      incidence of post-operative complications without influencing the prognosis.

PMID- 17038247
TI  - [Effect of nutritional support on immunity function in the acquired immune
      deficiency syndrome patients].
AB  - OBJECTIVE: To investigate the effect of nutritional support on immunity function
      in the acquired immune deficiency syndrome (AIDS) patients. METHODS: Sixty-five
      AIDS patients were randomly divided into treatment group (n=35) and control group
      (n=30). In the treatment group, the patients received enteral nutrition (EN)
      treatment or EN supplemented with parenteral nutrition (EN+PN) on top of routine
      treatment according to the daily condition of the sufferers. The control group
      received routine treatment only. CD3, CD4 and CD8 cell, CD4/CD8, C3, C4,
      immunoglobulin G (IgG), IgM, IgA were determined on the 0 and 30th day of the
      treatment, and they were analyzed with covariance analysis. RESULTS: CD4 cell in
      the treatment group was significantly raised compared with before examination
      (P<0.05). Other immunity indexes were not correlated. All clinical indexes showed
      no change in the control group (all P>0.05). CONCLUSION: The nutritional support
      can raise the immunity function in the AIDS patient.

PMID- 17038248
TI  - [Experimental study on gut tolerance to early enteral nutrition following
      intestinal ischemia/reperfusion].
AB  - OBJECTIVE: To investigate the effects of early enteral nutrition (EEN) on
      intestinal function and gut tolerance after intestinal ischemia/reperfusion (I/R)
      injury. METHODS: Twenty-four male dogs were randomly divided into three groups:
      EEN only, I/R only and I/R+EEN. The superior mesenteric artery (SMA) was blocked
      for 1 hour followed by restoration of blood flow. EEN was given 4 hours after
      reperfusion by continuous infusion of Fresubin nutrition fluid (4 ml.kg(-1).h(
      1), Fresenius Kabi Co, Germany) into gut via a tonometric catheter for 3 hours
      till intolerance symptoms, which including vomiting and diarrhea which indicated
      gut intolerance. CO(2) partial pressure of intestinal mucosa (PiCO(2)), D-xylose
      absorption and intestinal luminal pressure were measured to reflect intestinal
      function and perfusion. RESULTS: Incidence and severity of diarrhea and vomiting
      were significantly higher in I/R+EEN group (with 87.5% intolerance) than those in
      I/R only group (12.5%) and EEN only group (0). After EEN, PiCO(2) and intestinal
      cavity pressure were significantly higher, and the D-xylose absorption much
      lower, in the I/R+EEN group compared with the I/R group and EEN group (all
      P<0.01). CONCLUSION: Intestinal I/R may result in decreased tolerance to EEN. Too
      early enteral nutrition (less than 12 hours after gut hypoperfusion) may enhance
      intestinal ischemia injury and further inhibit its function of propulsion and
      absorption.

PMID- 17038249
TI  - [Protective effects of enteral immuno-nutrition on intestinal mucosa injury in
      burned rats].
AB  - OBJECTIVE: To investigate the protective effects of enteral immuno-nutrition on
      intestinal mucosa injury following severe burn. METHODS: Sixty-four Wistar rats
      with 30% total body surface area (TBSA) full-thickness burn were randomly divided
      into enteral nutrition (EN, n=32) group and enteral immuno-nutrition (EIN, n=32)
      group. Another 8 Wistar rats were used as normal control group. The concentration
      of secretory immunoglobulin A (sIgA) in intestinal mucosa, the blood levels of
      diamine oxidase (DAO) activity and tumor necrosis factor-alpha (TNF-alpha) were
      determined, and the expression of TNF-alpha mRNA in intestinal mucosa was
      determined by reverse transcription polymerase chain reaction (PT-PCR) in control
      group and on 1st, 4th, 7th, and 10th day postburn in EN and EIN group. RESULTS:
      Compared with that of before injury, the blood levels of DAO activity, TNF-alpha
      content, the concentration of sIgA and the expression of TNF-alpha mRNA in
      intestinal mucosa were significantly increased in both EN and EIN groups (P<0.05
      or P<0.01). However, the blood levels DAO activity, TNF-alpha content, the
      concentration of sIgA on 4th, 7th and 10th postinjury days and the expression of
      TNF-alpha mRNA in intestinal mucosa on 1st, 4th, 7th and 10th days postinjury in
      EIN group were significantly lower than those in EN group (P<0.05 or P<0.01).
      CONCLUSION: EIN can ameliorate the damage of the intestinal mucosa in burned rats
      compared with EN group. This might be related to an increase in the sIgA level
      and reduction of the expression of TNF-alpha mRNA in intestinal mucosa.

PMID- 17038251
TI  - [Comparative study on influence of enteral and parenteral nutrition on organ
      function in critically ill patients].
AB  - OBJECTIVE: To evaluate the protective effect of enteral nutrition on organ
      function in critically ill patients. METHODS: Forty-two critically ill patients
      were randomly divided into enteral nutrition group (n=14), total parenteral
      nutrition group (n=14), and control group (n=14). The partial pressure of oxygen
      in artery (PaO(2)), partial pressure of carbon dioxide in artery (PaCO(2)), white
      blood cell count (WBC) and the plasma contents of serum alanine aminotransferase
      (ALT), blood urea nitrogen (BUN), and the percentage of gastrointestinal
      haemorrhage were determined one week after the nutritional support was initiated.
      RESULTS: The WBC, the plasma contents of ALT, and the incidence of
      gastrointestinal haemorrhage were significantly higher in control group patients
      [(11.70+/-2.85)x10(9)/L, (59.69+/-20.32) U/L, 42.9%] than those in enteral
      nutrition group patients [(9.62+/-3.30)x10(9)/L, (40.68+/-22.11) U/L, 21.4%,
      P<0.05] and total parenteral nutrition group[(9.82+/-3.50)x10(9)/L, (40.98+/
      21.87) U/L, P<0.05, 42.9%], However, PaO(2) in control group patients (62.78+/
      4.95) mm Hg was markedly lower than those in enteral nutrition group and
      parenteral nutrition group patients [(80.85+/-14.03) mm Hg, (79.88+/-13.73) mm
      Hg, both P<0.05]. There was no significant difference in PaCO(2) and the plasma
      contents of BUN among the three groups 1 week after treatment were given (all
      P>0.05). CONCLUSION: Early stage enteral nutrition could well surpass total
      parenteral nutrition. It is conducive to protecting gastrointestinal function,
      preventing bacterial translocation, alleviating systemic inflammatory response
      and subsequent multiple organ failure among critically ill patients.

PMID- 17038255
TI  - [Effects of glutamine given through different avenues on intestine mucosal
      barrier function in burned rats].
AB  - OBJECTIVE: To observe the effect of glutamine given through different avenues on
      intestine mucosal barrier damage induced by severe burn injury. METHODS: One
      hundred and sixty Wistar rats were randomly divided into four groups: namely
      normal control (C group), burned control (B group), parenteral nutrition with
      glutamine (PN+GLN group) and enteral nutrition with glutamine (EN+GLN group).
      Rats in B group, PN+GLN group, and EN+GLN group were subjected to 30% total body
      surface area (TBSA) full-thickness burn injury. In the latter three groups,
      nutritional intake was isonitrogenous and isocaloric. In PN+GLN group and EN+GLN
      group the nutrition were supplemented with glutamine 1.0 g.kg(-1).d(-1), and in B
      group tyrosine 1.0 g.kg(-1).d(-1). Indexes relevant to injury to the intestine
      were determined on postburn day (PBD) 1, 3, 5, 7 and 10. RESULTS: After burn
      injury, the index of intestinal mucosal injury, intestine mucosal permeability
      and the activity of plasma diamine oxidase (DAO) were significant increased
      compared with C group (all P<0.01). On the other hand, the intestine mucosal
      blood flow (IMBF), mucosa thickness, villous height, crypt depth and intestinal
      epithelial proliferation index were significantly decreased (P<0.05 or P<0.01).
      Compared with B group, the extent of changes in these indices were lowered in
      PN+GLN group and EN+GLN group (P<0.05 or P<0.01), and the effects were more
      marked in EN+GLN group than those in PN+GLN group. CONCLUSION: GLN is beneficial
      in minimizing intestinal injury, promoting intestinal mucosal repair. Enteral
      supplementation of GLN is a better way of administration.

PMID- 17038253
TI  - [Effect of total parenteral nutrition with supplementation of glutamine on the
      plasma diamine oxidase activity and D-lactate content in patients with multiple
      organ dysfunction syndrome].
AB  - OBJECTIVE: To explore the effect of total parenteral nutrition (TPN) supplemented
      with glutamine on the activity of plasma diamine oxidase (DAO) and D-lactate
      content in blood of patients with multiple organ dysfunction syndrome (MODS).
      METHODS: Forty patients with MODS in the intensive care unit (ICU) from September
      2003 to June 2005 were involved in a randomized controlled study, and divided
      into routine group (group A, n=20), the glutamine +TPN treatment group (group B,
      n=20). All patients received equivalent nitrogen and caloric values in parenteral
      nutrition. Group A was given routine TPN, and group B was given extra glutamine
      0.27 g.kg(-1).d(-1) (i. e. dipeptiven 0.4 g.kg(-1).d(-1)) for 7 days. The
      activity of plasma DAO and D-lactate content, the treatment time and the
      mortality rate of the two groups were determined before TPN, on the 1st, the 3rd
      and the 7th day after TPN. At the same time, 20 healthy blood donors formed the
      healthy control group (group C). All the data were analyzed with the SPSS 10.0
      software. RESULTS: Before treatment, the activity of plasma DAO and D-lactate
      content of the two patient groups were significantly higher than those of group C
      (both P<0.01), and there was no difference between group A and group B (P>0.05).
      After the treatment of glutamine supplemented TPN, the activity of plasma DAO and
      D-lactate content of group B were lower than those of group A (both P<0.01). The
      duration of TPN was (15.8+/-2.3) days for group A and (12.5+/-2.4) days for group
      B. The former was significantly longer than that of group B (P<0.05). The
      mortality rate of group A was 25%, the mortality rate of group B was 10%, but
      there was no significant difference between the two groups (P>0.05). CONCLUSION:
      The glutamine (dipeptiven) supplementation through vein can help increase the
      supply of energy substrate to intestinal mucosa epithelium, and decrease the
      activity of plasma DAO and D-lactate content. It has an important effect on
      protecting the intestinal mucosa epithelial function. It also helps shorten the
      TPN treatment course.

PMID- 17038256
TI  - [The time for beginning of enteral nutrition in traumatic shock].
AB  - OBJECTIVE: To explore the value of monitoring CO(2) partial pressure of gastric
      mucosa (PiCO(2)) in patients with traumatic shock under enteral nutrition (EN)
      support. METHODS: Ninety-six patients who were clinically diagnosed as having
      traumatic shock were randomly divided into two groups: the test group and the
      control group. In the test group, EN was given after tissue oxygenation,
      indicated by the value of PiCO(2), approached normal and the clinical symptoms
      ameliorated. In control group EN was given at the early stage of recovery from
      shock. The course of convalescence of the primary disease, gastro-intestinal
      symptoms, the monitoring indexes, and the complications etc. were compared
      between the two groups. RESULTS: Acute physiology and chronic health evaluation
      II (APACHE II) scores were both gradually lowered in both groups. It was more
      significant in the control group than that in the test group 5 days later (both
      P<0.01). Compared with the control group, the cure rate in the test group was
      increased obviously (91.3% vs. 75.0%, P<0.01), and the hospital stay days were
      significantly less [(6.0+/-1.8) days vs. (7.5+/-2.3) days, P<0.01]. CONCLUSION:
      It is very important to choose the suitable time to give EN support in patients
      with traumatic shock, for it can protect and promote the recovery of the function
      of their intestinal tract, raise the survival rate.

PMID- 17038266
TI  - Cardiovascular risk factors in adolescents.
AB  - Most children who are normal weight for height and otherwise healthy have risk
      factor levels associated with the absence of heart disease (ie, they do not
      smoke, do not have diabetes, are physically active, have low-density lipoprotein
      levels < 110 mg/dL, and have blood pressure < 120/80 mm Hg). However, by
      adolescence, the earliest lesions in the atherosclerotic process, fatty streaks
      and raised lesions, are present in the coronary arteries and the abdominal aorta.
      The severity of early atherogenesis is related to the coexistence of the major
      cardiovascular risk factors. Most commonly, the associated risk disturbances are
      mild: borderline hypertension, mild dyslipidemia, insulin resistance, overweight,
      physical inactivity, and initiation of tobacco use. Rarely, more severe risk
      factors are present: familial hypercholesterolemia (a genetic disorder of lipid
      metabolism), diabetes mellitus, secondary hypertension of long standing, or risk
      factors associated with chronic conditions such as end-stage renal disease. Thus,
      cardiovascular risk management in this age group has two components: primordial
      prevention (the prevention of the development of cardiovascular risk in the first
      place) and primary prevention (more aggressive treatment of identified risk
      factors in high-risk individuals either through behavioral or pharmacologic
      means). Trials beginning in adolescence of the primary prevention of
      atherosclerosis-related diseases have not been undertaken; thus, the decision to
      initiate pharmacologic management in high-risk adolescents requires careful
      thought.

PMID- 17038267
TI  - Smoking, smoking cessation, and risk of cardiovascular disease.
AB  - Cigarette smoking increases the risk of atherothrombotic clinical events such as
      myocardial infarction and the effect is dose dependent for persons who continue
      to smoke. Reductions in smoking habit and smoking cessation are important ways to
      improve cardiovascular risk and favorably affect primary and secondary prevention
      of clinical disease. Therapeutic methods to improve smoking reduction and
      cessation include nicotine replacement, behavioral interventions, and medications
      (bupropion, clonidine). Improved cessation rates are under active study and
      include behavioral methods, targeting smokers immediately after myocardial
      infarction, consideration of depression in smokers, pharmacogenomics to identify
      persons who may respond more favorably to specific interventions, and newer
      medications that affect endocannabinoid receptors.

PMID- 17038268
TI  - LDL-apheresis therapy.
AB  - Low-density lipoprotein (LDL)-apheresis is an effective means for acutely
      lowering plasma cholesterol (LDL reduction > 60%) and reducing cardiovascular
      events in patients with uncontrolled hypercholesterolemia who are genetically
      predisposed or resistant to standard therapy. Despite its known benefit,
      apheresis is performed in only a minority of qualified patients. In addition to
      reducing plasma cholesterol, apheresis can alter other markers of vascular
      disease (inflammation, rheology, thrombosis, and fibrinolysis). The acute and
      chronic changes to the vascular system may warrant LDL-apheresis use in other
      diseases.

PMID- 17038269
TI  - Low-density lipoprotein cholesterol lowering in the prevention of CHD: how low
      should we go?
AB  - The past 12 years have seen the publication of numerous randomized placebo
      controlled studies using statins to lower low-density lipoprotein cholesterol
      (LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events.
      Initial studies predominantly evaluated mortality or nonfatal myocardial
      infarctions and coronary heart disease (CHD) death in patients with known or
      presumed established coronary disease and moderately elevated to very elevated
      serum cholesterol concentrations. Subsequent investigations studied a broader
      spectrum of cardiovascular events as a composite primary end point in both
      primary and secondary prevention strategies in subjects with lower mean entry
      serum LDLC concentrations. These studies have generally shown a reduction in a
      composite end point of cardiovascular events, although not necessarily the more
      restricted end points used in previous studies. Although the LDLC mantra "lower
      is better" has been popularized in advertising and continuing medical education
      and suggested as an option in "very high risk" patients by the National
      Cholesterol Education Program Adult Treatment Panel, the precise target level for
      LDLC for optimal treatment has not been rigorously defined. Serum LDLC less than
      100 mg/dL seems reasonable for patients with known atherosclerosis or at high
      risk for atherosclerosis (diabetes or presence of multiple risk factors). Serum
      LDLC less than 70 mg/dL may be a reasonable goal in the setting of acute coronary
      syndromes, but there are many problems with the data on which this recommendation
      is made. Furthermore, many advocates of "lower is better" seem oblivious to the
      potential downsides of more aggressive lipid-lowering therapy. The LDLC target in
      lower risk primary prevention is less clear. What is obvious is that moderate
      dose statin therapy can lower CHD risk in primary prevention and secondary
      prevention with minimal side effects, and with the imminent availability of
      several generic statins, with great cost-effectiveness.

PMID- 17038270
TI  - The role of ultrafiltration in the management of heart failure.
AB  - In the United States, 90% of one million annual hospitalizations for heart
      failure are due to symptoms of volume overload. Hypervolemia contributes to heart
      failure progression and mortality. Treatment guidelines recommend that therapy
      for patients with heart failure be aimed at achieving euvolemia. Intravenous loop
      diuretics induce a rapid diuresis that reduces lung congestion and dyspnea.
      However, loop diuretics' effectiveness declines with repeated exposure.
      Unresolved congestion may contribute to high re-hospitalization rates.
      Furthermore, loop diuretics may be associated with increased morbidity and
      mortality due to deleterious effects on neurohormonal activation, electrolyte
      balance, and cardiac and renal function. Ultrafiltration is an alternative method
      of sodium and water removal, which safely improves hemodynamics in patients with
      heart failure. Application of this technology has been limited by the need for
      high flow rates, large extracorporeal blood volumes, and large-bore central
      venous catheters. A modified ultrafiltration device has overcome these
      limitations. Ultrafiltration may be a safe and effective alternative to
      intravenous diuretics in the treatment of decompensated heart failure.

PMID- 17038271
TI  - The role of exercise therapy in the treatment of patients with systolic heart
      failure.
AB  - The predominant benefits of exercise training in systolic heart failure have been
      seen with aerobic training, although some information exists for the beneficial
      effects of resistive training as well. Although men clearly benefit from exercise
      training, the effects of exercise in women are less clear. Most of the studies
      have used supervised training 3 to 5 days a week for 8 weeks to 6 months, with 30
      to 60 minutes of exercise per session. However, home exercise has been reported
      in a few studies, and appears to be safe and possibly efficacious. The effects of
      training on mortality are unknown at this time, although no study has
      demonstrated increased adverse events associated with training. Exercise training
      should be recommended for patients with stable New York Heart Association class
      II to III heart failure.

PMID- 17038272
TI  - The management of atrial fibrillation in heart failure.
AB  - The development of atrial fibrillation (AF) can greatly complicate the course of
      heart failure (HF). Although recent trials have indicated the nonsuperiority of a
      rhythm control strategy in the general population with AF, this may not apply to
      patients with HF. We feel strongly that AF be treated aggressively in patients
      with HF, defaulting toward an initial rhythm control strategy, to avoid the
      hemodynamic detriment of irregular rapid ventricular response and the development
      of tachycardia-related myopathy. The index episode is treated with cardioversion
      and antiarrhythmic therapy. If significant benefit is demonstrated, the rhythm
      control strategy is maintained, to the point of catheter ablation for AF if
      necessary. If there is no change in cardiac performance or symptoms after
      cardioversion, strict rate control is enforced, to the point of atrioventricular
      node ablation and pacing if necessary.

PMID- 17038273
TI  - Goals and guidelines for treating hypertension in a patient with heart failure.
AB  - Hypertension promotes left ventricular (LV) hypertrophy and myocardial remodeling
      and is frequently present in patients with systolic or diastolic heart failure.
      Control of hypertension in both of these settings may attenuate progressive LV
      hypertrophy and remodeling and improve clinical outcomes. Guidelines for the
      management of heart failure recommend that hypertension should be treated in all
      patients with preclinical heart failure as well as in those with heart failure
      with reduced or preserved LV systolic function. Consistent with national
      hypertension guidelines, the goal for blood pressure control in hypertensive
      patients with heart failure is less than 140/90 mm Hg, but lower targets (<
      130/80 mm Hg) may be desirable in those with concomitant diabetes mellitus or
      renal disease. Angiotensin-converting enzyme inhibitors, angiotensin II receptor
      antagonists, and beta-adrenoreceptor antagonists are first-line options for
      hypertension treatment in heart failure. Calcium channel antagonists and the
      alpha blocker doxazosin should be avoided. Episodes of recurrent pulmonary edema
      and hypertension may also indicate underlying severe renovascular disease that
      may respond to percutaneous renal artery intervention.

PMID- 17038274
TI  - Arthrodesis of the subtalar and talonavicular joints for correction of
      symptomatic hindfoot malalignment.
AB  - BACKGROUND: Triple arthrodesis has long been used for the treatment of painful
      malalignment or arthritis of the hindfoot. However, the effect of fusion on
      adjacent joints has sparked interest in a more limited arthrodesis in patients
      without involvement of the calcaneocuboid joint. METHOD: Results of 16 feet in 14
      patients who had a modified double arthrodesis for symptomatic flatfoot,
      cavovarus deformity, or hindfoot arthritis were reviewed retrospectively with a
      minimum followup of 18 (range 18 to 93) months. The most common diagnosis
      contributing to the hindfoot deformity was pes planovalgus. All operations were
      done with a consistent technique using rigid internal fixation with screws. In 15
      feet, a concomitant gastrocnemius recession for equinus contracture was done at
      the time of the primary surgery. Clinical evaluation was based on the American
      Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale in addition to
      subjective assessments of pain, function, shoewear, cosmesis, and overall
      satisfaction. Radiographic evaluation included measurements of the anterior
      posterior talo-second metatarsal angle, lateral talocalcaneal angle, and lateral
      talo-first metatarsal angle, and notation of arthritic changes of the ankle,
      calcaneocuboid, and midfoot joints, as well as an assessment of time to union of
      all arthrodeses. RESULTS: The average AOFAS Ankle-Hindfoot Scale improved from
      44.7 preoperatively to 77.0 postoperatively (p < 0.01). Subjectively, patients
      experienced improvements in pain, function, cosmesis, and shoewear. Overall, all
      patients were satisfied and would have the procedure again under similar
      circumstances. Radiographically, all parameters statistically improved. There was
      an increase in arthritic scores for six ankle, six calcaneocuboid, and five
      midfoot joints. One talonavicular joint nonunion occurred in a rheumatoid
      patient, requiring revision arthrodesis. CONCLUSIONS: We have concluded that
      simultaneous arthrodesis of the talonavicular and subtalar joints is a reasonable
      treatment in the subset of patients with symptomatic hindfoot malalignment whose
      calcaneocuboid joints are not involved in the primary disease.

PMID- 17038275
TI  - Lateral trans-biceps popliteal block for elective foot and ankle surgery
      performed after induction of general anesthesia.
AB  - BACKGROUND: The purpose of this study was to determine safety and efficacy of
      lateral transtendinous popliteal blocks performed after induction of general
      anesthesia for intraoperative and postoperative pain control in elective foot and
      ankle surgery. METHODS: The charts of 475 consecutive patients were
      retrospectively reviewed. The technique was a lateral transtendinous popliteal
      block under nerve stimulator direction (described in the text). Patient records
      were retrospectively evaluated from the postanesthesia care unit, as well as at
      followup on postoperative day 1 and weeks 2, 6, and 12. RESULTS: The block was
      complete in 398 patients (83.7%). An incomplete block was found in 77 patients
      (16.2 %). In the incomplete category, 21 patients (4.4%) had no pain but some
      motor function, 32 patients (6.5%) reported mild to moderate pain, and 24
      patients (5.3%) had severe pain. The average block duration was 16.5 hours. There
      were no adverse effects documented in any patient at followup. CONCLUSIONS:
      Lateral popliteal nerve block after induction of general anesthesia appears to be
      safe and effective for intraoperative and postoperative pain control in elective
      foot and ankle surgery.

PMID- 17038276
TI  - The long-term outcome of tendon lengthening for chronic Achilles tendon pain.
AB  - BACKGROUND: The purpose of this study was to assess the long-term results of
      tendon lengthening surgery for the treatment of chronic Achilles tendon pain.
      METHODS: The results of 21 procedures in 18 patients were assessed. Each patient
      had an open Z-plasty to lengthen the Achilles tendon by 1 cm. RESULTS: Results
      showed a long-term (7.5 years) reduction in visual analogue pain scores for
      sporting activity in 20 of 21 procedures (median 50 point reduction, p < 0.0005).
      The tendon lengthening was apparent in a mean increase in dorsiflexion of 5
      degrees. Two patients had minor gait abnormalities postoperatively. One patient
      had a reduction in plantarflexion power on the operated side, but five patients
      had improved power compared to the nonoperated limb. One major and five minor
      surgical complications were noted. CONCLUSIONS: The retrospective nature of this
      study must be noted in drawing conclusions. However, the results suggest
      excellent long-term reduction of Achilles pain after tendon lengthening. This
      must be weighed against a relatively high complication rate for any procedure in
      this region. This treatment does not appear to cause long-term deficits in
      plantarflexion power or gait.

PMID- 17038277
TI  - Technique and results of Achilles tendon detachment and reconstruction for
      insertional Achilles tendinosis.
AB  - BACKGROUND: Insertional Achilles tendinosis is a clinical entity that commonly
      occurs with other posterior heel disorders such as retrocalcaneal bursitis,
      Haglund deformity, intratendinous ossification and pretendinous bursitis.
      Complete detachment and reconstruction of the Achilles tendon was evaluated as a
      method of treatment for this condition. METHODS: Seventy-five patients (81 heels)
      were treated over a 5-year period for chronic insertional Achilles tendinosis.
      These were divided in two groups: a nondetached group (26 patients, 31 heels,
      average age 55 years) included all patients with debridement of the Achilles
      tendon with no or partial detachment of the tendon, and a detached group (49
      patients, 50 heels, average age 56.1 years) that included all patients with
      complete detachment, debridement, and reattachment with suture anchors of the
      Achilles tendon associated with proximal V-Y lengthening of the proximal
      aponeurosis. Sixty-one patients (65 heels) were contacted for an interview
      questionnaire, 22 patients from the nondetached group (26 heels) and 39 patients
      from the detached group (39 heels). The average followup for the nondetached
      group was 47 months and for the detached group 33 months. Items evaluated
      included pain, activity limitation, gait change, walking distance, return to
      sport or work, and level of satisfaction. RESULTS: No statistically significant
      differences were noted in relation to any of the items evaluated. In the
      nondetached group, the satisfaction rate was 92%, and 8% were dissatisfied. In
      the detached group, 74% were completely satisfied and 18% were satisfied with
      reservations. Eight percent were dissatisfied. Complications included minor wound
      dehiscence (one in the nondetached, five in the detached group), wound infection
      (one in the nondetached group, two in the detached group) and sural neuritis (two
      in the detached group). CONCLUSIONS: Complete detachment of the Achilles tendon
      and reattachment with suture anchors and a proximal V-Y lengthening was a
      reliable and effective method of treatment for severe chronic insertional
      Achilles tendinosis as was debridement of the tendon insertion without detachment
      for less severe involvement.

PMID- 17038278
TI  - The use of standing lateral tibial-calcaneal angle as a quantitative measurement
      of Achilles tendon contracture in adult acquired flatfoot.
AB  - BACKGROUND: To quantitate the association of Achilles tendon contracture (ATC)
      with adult acquired flatfoot, the authors hypothesized that the standing lateral
      tibial-calcaneal angle increases because of ATC. METHODS: The standing lateral
      tibial-calcaneal angle, talo-first metatarsal angle, lateral talocalcaneal angle,
      lateral standing medial cuneiform, arch height, and anteroposterior talonavicular
      coverage angle were measured in 21 patients (25 feet) with clinical diagnoses of
      ATC and adult acquired flatfoot (AAF) and compared to the same measurements in a
      control group of 15 patients (30 feet) with no foot deformities or previous foot
      surgeries. RESULTS: The mean lateral tibial-calcaneal angle in the control group
      was 64.43 degrees and in the AAF group 71.24 degrees (p < 0.001). The mean
      lateral talo-first metatarsal angle in the control group was 11.77 degrees, and
      in the AAF group with ATC it was 25.80 degrees (p < 0.001). The mean arch height
      in the control group was 17.90 mm and in the AAF group, 8.48 mm (p < 0.001). In
      the ATC and AAF group an increasing standing lateral tibial-calcaneal angle was
      correlated with a decreasing lateral talo-calcaneal angle (p = 0.044), and a
      decreasing arch height was correlated to an increasing lateral talo-first
      metatarsal angle (p < 0.001). CONCLUSION: Adults with flatfeet and Achilles
      tendon contracture may have a statistically significant increase in the standing
      lateral tibial-calcaneal angle. This angle may be a reproducible measure of ATC.
      An increase in the standing lateral tibial-calcaneal angle may confirm and
      quantitate the clinical diagnosis of Achilles tendon contracture. Further studies
      with more patients are needed.

PMID- 17038279
TI  - Flexor hallucis longus tendon transfer for hallux claw toe deformity and vertical
      instability of the metatarsophalangeal joint.
AB  - BACKGROUND: Historically, operative treatment of hallux claw toe deformity has
      been the Jones procedure or one of its modifications. Review of the literature
      confirms its ability to maintain alignment and achieve patient satisfaction;
      however, several complications have been reported. Many of these are related to
      altered biomechanics across the metatarsophalangeal (MTP) joint. A similar
      approach to this clinical problem involves restoration of the flexion moment
      across the MTP joint without an interphalangeal (IP) joint arthrodesis. METHODS:
      We conducted a retrospective review of 10 patients who had a flexor hallucis
      longus (FHL) tendon transfer to the proximal phalanx of the great toe for hallux
      claw toe deformity, as well as for symptomatic vertical instability. Four
      patients had a positive drawer test indicating vertical instability without
      static deformity. Two patients with vertical instability were found to have a
      dynamic deformity. Mean followup was 24 (SD 15.2) months. RESULTS: All
      deformities were corrected and alignment was maintained at the time of followup.
      Pain under the first metatarsal head was reliably improved in symptomatic
      patients (p < 0.05). Patient satisfaction also was assessed. All six patients
      treated for hallux claw deformity were satisfied with their outcomes. Two of the
      four patients treated for vertical instability were satisfied. The other two
      patients expressed dissatisfaction because of persistent pain that occurred
      during strenuous exercise. Their symptoms during routine activity were improved,
      however. CONCLUSION: Based on initial results, the FHL transfer to the proximal
      phalanx appears to be a viable treatment option for hallux claw deformity in
      terms of deformity correction, pain relief, and patient satisfaction. Further
      evaluation is warranted regarding the indication of vertical instability.

PMID- 17038280
TI  - Thromboembolic disease after foot and ankle surgery.
AB  - BACKGROUND: The incidence and potential life-threatening complications of
      thromboembolic disease after major orthopaedic surgery has been extensively
      studied. However, there are two studies pertaining to the incidence of
      thromboembolic disease after foot and ankle surgery, the findings of which
      suggest that the incidence is too low to justify routine thromboprophylaxis.
      METHODS: This is a retrospective study identifying the incidence of
      thromboembolic disease after foot and ankle surgery in the practices of two foot
      and ankle specialists. The purpose of the study was to evaluate the risk factors
      for the development of thromboembolic disease and to examine the issue of routine
      thromboprophylaxis. Six hundred and two patients were included in this study.
      RESULTS: There was a 4% incidence (24 patients) of postoperative thromboembolic
      complications. Risk factors identified for postoperative thromboembolic disease
      were a history of rheumatoid arthritis, a recent history of air travel, previous
      deep vein thrombosis or pulmonary embolism, and limb immobilization. CONCLUSIONS:
      The incidence of thromboembolic disease after foot and ankle surgery could be
      higher than that previously reported particularly if a patient has certain risk
      factors. Prospective randomized clinical trials are needed to establish the true
      incidence of thromboembolic disease after foot and ankle surgery and to define
      the indications for routine thromboprophylaxis.

PMID- 17038281
TI  - Diagnosis and treatment of malignant melanoma of the foot.
AB  - BACKGROUND: Patients diagnosed with melanoma of the foot have been reported to
      have a poor prognosis. We reviewed our experience at a tertiary-care medical
      clinic to determine the disease course in patients diagnosed with melanoma of the
      foot. METHODS: A retrospective review was performed of 38 patients with a
      diagnosis of primary or locally recurrent melanoma of the foot treated between
      January, 1988, and July, 2004. The main outcome measures included methods of
      diagnosis, clinical and histopathologic features, and patterns of recurrence.
      RESULTS: The mean age at diagnosis was 61 years; most were women (58%) and
      Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical
      diagnosis had been considered benign in 12 (32%). The median Breslow thickness
      was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma
      accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph
      node biopsy specimens of 25 patients identified four (16%) with metastatic
      disease. Surgical complications occurred in 12 patients, usually after skin graft
      or soft-tissue flap reconstruction. Systemic recurrence developed in six
      patients, four of whom also had regional recurrence. CONCLUSIONS: Most patients
      were elderly Caucasian women and most presented with early-stage disease, but
      diagnosis can be difficult and a subgroup presented with thick melanomas.
      Reconstructive surgical procedures had a high rate of complications; however,
      overall functional outcomes were good. Stage of cancer at diagnosis was
      associated with systemic metastases.

PMID- 17038282
TI  - A cotton batting compression dressing and fiberglass cast used safely in the
      immediate postoperative period after hindfoot or ankle surgery.
AB  - BACKGROUND: Patients undergoing surgery on the foot and ankle who require
      immobilization are typically placed in splints or soft compression dressings
      after surgery to avoid complications associated with swelling. As swelling
      subsides, this temporary immobilization is removed and replaced with a short-leg
      cast, making an additional office visit necessary, which adds to the cost as well
      as patient discomfort. METHODS: We apply a cast in the operating room using a
      special padding technique to accommodate postoperative swelling. It is supportive
      enough that it does not need to be replaced shortly after surgery. This cast was
      applied to 38 patients having surgery on the hindfoot or ankle between March,
      2003, and February, 2004. RESULTS: All patients tolerated the cast during the
      initial 2 weeks after surgery, and there were no complications. CONCLUSION: The
      purpose of this study was to describe the casting technique and document its
      safety for use immediately after surgery on the hindfoot and ankle.

PMID- 17038283
TI  - Midline posterior approach to the ankle and hindfoot.
AB  - BACKGROUND: The posterior approach to the ankle and hindfoot can be used for
      fixation of fractures, fusions, or osteotomies and is especially useful in
      patients with poor soft tissue anteriorly, medially, or laterally. However, a
      high rate of wound complications has been reported with standard posterolateral
      and posteromedial approaches. Because of local wound problems with the standard
      approaches, we have used a midline posterior approach and a longitudinal midline
      splitting of the Achilles tendon. This approach provides excellent exposure while
      minimizing wound healing complications. This approach provides dissection between
      angiosomes, which should optimize preservation of the blood supply to the skin
      flaps. METHODS: We retrospectively evaluated wound healing in 33 consecutive
      patients who had surgery using the modified midline posterior approach. The mean
      age of the patients was 48 (range 16 to 83) years. The mean followup was 24
      (range 12 to 73) months. Surgical procedures included ankle and pantalar
      arthrodeses (primary and revision), talectomies with tibiocalcaneal arthrodesis,
      repairs of fracture nonunions, reconstruction of a chronic Achilles rupture, and
      hardware removal with multiple debridements of chronic osteomyelitis. RESULTS:
      There were no instances of skin flap necrosis. One patient with diabetic
      neuropathic arthropathy developed a small superficial wound eschar that healed
      with dressing changes alone. Four patients developed deep infections; two of
      these had a history of deep infection and the other two had significant
      comorbidities. CONCLUSIONS: The modified midline posterior approach to the distal
      tibia, ankle, and hindfoot has a low primary wound complication rate without
      sacrificing exposure. This approach can be used for any procedure requiring
      posterior access to the distal tibia, ankle joint, or subtalar joint.

PMID- 17038284
TI  - Instant 99mTc-ciprofloxacin scintigraphy for the diagnosis of osteomyelitis in
      the diabetic foot.
AB  - BACKGROUND: The diagnosis of osteomyelitis of the foot in patients with diabetes
      mellitus remains a challenge. This study was conducted to evaluate bone
      infections using scintigraphy with instantly prepared single-vial kit, radio
      labeled ciprofloxacin (Diagnobact TM) in comparison to a bacterial culture taken
      from the involved site. METHODS: Twenty-five patients with type 2 diabetes
      mellitus having foot ulcers, including six with superficial ulcers and positive
      99mTc-methylene diphosphonate (MDP) bone scan as a control, were subjected to
      99mTc-ciprofloxacin scan and subsequent bacteriological culture. RESULTS: 99mTc
      ciprofloxacin scan was positive in 13 patients and negative in 12 patients,
      including the six with superficial ulcers. Bacterial culture was positive in 18
      patients and negative in seven, including one with osteomyelitis on bone biopsy
      only. 99mTc-ciprofloxacin scan showed "true positive" results in 12, "true
      negative" in six, "false positive" in one, and "false negative" in six. The
      specificity and sensitivity of the test were 66.7% and 85.7%, respectively. The
      positive and negative predictive values and an accuracy of 92.8%, 50% and 72%,
      respectively. Staphylococcus aureus and Escherichia coli were the most frequently
      isolated organisms. CONCLUSION: 99mTc-ciprofloxacin is a sensitive and specific
      marker to diagnose bone infection in patients with diabetes mellitus, but care
      must be taken in case of fastidious organisms and ciprofloxacin-resistant
      bacterial flora in which false results may be obtained.

PMID- 17038285
TI  - Gliding resistance of the posterior tibial tendon.
AB  - BACKGROUND: Abnormal gliding of the posterior tibial tendon may lead to
      mechanical trauma, degeneration, and eventually posterior tibial tendon
      dysfunction. Our study analyzed the gliding resistance of the posterior tibial
      tendon in intact feet and in feet with simulated flatfoot deformity. METHODS: An
      experimental system was developed that allowed direct measurement of gliding
      resistance at the tendon-sheath interface. Seven normal fresh-frozen cadaver foot
      specimens were studied, and gliding resistance between the posterior tibial
      tendon and sheath was measured. The effects of ankle and hindfoot position and
      the effect of flatfoot deformity on gliding resistance were analyzed. Gliding
      resistance was measured for 4.9 N applied load to the tendon. RESULTS: Mean
      gliding resistance for the neutral position was 77 +/- 13.1 (x10(-2) N). Compared
      to neutral position, dorsiflexion increased gliding resistance and averaged 130
      +/- 38.9 (x10(-2) N), and plantarflexion decreased gliding resistance and
      averaged 35 +/- 12.6 (x10(-2) N). Flatfoot deformity increased gliding resistance
      compared to normal feet, averaging 104 +/- 17.0 (x10(-2) N) for neutral, 205 +/-
      55.0 (x10(-2) N) for dorsiflexion, and 58 +/- 21.3 (x10(-2) N) for
      plantarflexion. CONCLUSIONS: The findings indicate that patients with a
      preexisting flatfoot deformity may be predisposed to develop posterior tibial
      tendon dysfunction because of increased gliding resistance and trauma to the
      tendon surface.

PMID- 17038286
TI  - Using resident input to identify and integrate essential components of a foot and
      ankle rotation.
AB  - BACKGROUND: Foot and ankle surgery is one of the orthopaedic subspecialties to
      which residents not uncommonly receive limited exposure. Therefore, it is
      important to identify what both faculty and residents regard as fundamental to a
      foot and ankle rotation. The purposes of this study were to identify the
      essential components of a foot and ankle rotation and to correlate these with the
      American Orthopaedic Foot and Society (AOFAS) core curriculum, and to discuss how
      to integrate resident input and AOFAS guidelines into a valued foot and ankle
      rotation. METHODS: Over a 5-year period, each orthopaedic resident beginning a 10
      week postgraduate year (PGY) 3 foot and ankle rotation was asked to choose topics
      to be covered during weekly 45-minute discussion conferences. Each resident also
      identified personal goals for the rotation. Data were collected in this
      prospective nature, and the responses of the 24 PGY 3 residents from our program
      who completed the rotation between February, 2000, and April, 2005, were
      analyzed. The discussion conference topics were compared to the AOFAS guidelines,
      and the top 10 personal goals were determined. Prerotation and postrotation
      Orthopaedic Inservice Training Examination (OITE) foot and ankle scores for the
      residents also were analyzed. RESULTS: Among the nine AOFAS core curriculum
      categories, residents most frequently chose chronic soft-tissue foot and ankle
      problems, followed in frequency by foot and ankle arthritis, foot and ankle
      trauma, and diabetic foot. Individually, posterior tibial tendon insufficiency,
      hallux valgus, diabetic foot, and calcaneal fracture were the most frequently
      chosen discussion conference topics. In regards to personal goals for the
      rotation, residents most commonly wanted to improve their physical examination
      skills (88%) and increase their orthotic knowledge (71%). The OITE scores
      improved by a mean of 12% after the rotation. CONCLUSIONS: This study provides
      new and detailed information about resident expectations for a valued foot and
      ankle rotation. These results should be integrated with existing AOFAS guidelines
      to further refine the essential components of a core foot and ankle curriculum.

PMID- 17038287
TI  - Crank-shaped arthrodesis for a flatfoot with a bipartite navicular: a case
      report.

PMID- 17038288
TI  - Internal rotation of the proximal fibular fragment producing symptomatic
      tibiofibular impingement after an SER-II ankle fracture: a case report.

PMID- 17038289
TI  - Plantar fracture-dislocation of the intermediate cuneiform: case report.

PMID- 17038290
TI  - Clinical tip: Late medial ankle pain as indicator of syndesmotic instability.

PMID- 17038291
TI  - Correction of severe valgus deformity during ankle arthrodesis: technique tip.

PMID- 17038292
TI  - Current concepts review: Stress fractures of the foot.

PMID- 17038293
TI  - Carotid artery stenting with distal protection using the carotid wallstent and
      filterwire neuroprotection: single-center experience of 380 cases with midterm
      outcomes.
AB  - Emerging data have supported the clinical efficacy of carotid artery stenting
      (CAS) in stroke prevention in high-risk surgical patients. This study was
      performed to evaluate the midterm clinical outcome of CAS using the Carotid
      Wallstent and FilterWire distal protection (both Boston Scientific, Natick, MA)
      at an academic institution. Risk factors for in-stent restenosis (ISR) were also
      analyzed. Clinical variables and treatment outcome of high-risk patients who
      underwent Carotid Wallstent placement with FilterWire EX/EZ neuroprotection were
      analyzed during a recent 54-month period. Three hundred eighty CAS procedures
      were performed in 354 patients. Technical success was achieved in 372 cases
      (98%), and symptomatic lesions existed in 85 (24%) patients. No patient
      experienced periprocedural mortality or neuroprotective device-related
      complication. The 30-day stroke and death rate was 2.7%, and the overall
      complication rate was 6.9%. The overall major or fatal stroke rates in
      symptomatic and asymptomatic patients were 4.6% and 1.3%, respectively (not
      significant). The overall stroke and death rates between the symptomatic and
      asymptomatic groups were 5.8% and 2.4%, respectively (not significant). The
      median follow-up period was 29 months (range 1-53 months). With Kaplan-Meier
      analysis, the rates of freedom from 60% or greater ISR after CAS procedures at
      12, 24, 36, and 48 months were 97%, 94%, 92%, and 90%, respectively. The rates of
      freedom from all fatal and nonfatal strokes at 12, 24, 36, and 48 months were
      97%, 91%, 89%, and 85%, respectively. Multivariable analysis of significant
      univariate predictors identified that postendarterectomy stenosis (odds ratio
      [OR] 3.98, p = .02) and multiple stent placement (OR 3.68, p = .03) were
      independent predictors of ISR. Our study yielded favorable short-term and midterm
      clinical results using Carotid Wallstent with FilterWire neuroprotection. Late
      follow-up results showed low rates of fatal and nonfatal stroke and favorable ISR
      rates compared with other carotid stent trials. Postendarterectomy and multiple
      stent placement were associated with subsequent ISR.

PMID- 17038294
TI  - Transcervical carotid stenting with flow reversal for neuroprotection: technique,
      results, advantages, and limitations.
AB  - Carotid angioplasty and stenting are progressively earning a role as a less
      invasive alternative in the treatment of carotid occlusive disease. The most
      common approach for carotid artery stenting involves transfemoral access and use
      of a filter or balloon device for neuroprotection. This approach has limitations
      related to both the site of access and the method of neuroprotection.
      Specifically, an aortoiliac segment with advanced occlusive or aneurysmal disease
      or an anatomically unfavorable or atheromatous arch and arch branches can
      significantly limit the safety of the retrograde transfemoral pathway to the
      carotid bifurcation. Additionally, data provided by the use of transcranial
      Doppler monitoring and diffusion-weighted magnetic resonance imaging in patients
      undergoing filter- or balloon-protected carotid artery stenting demonstrate that
      currently available devices are associated with a considerable incidence of
      cerebral embolization. To address these limitations, we, along with others, have
      employed a direct transcervical approach for carotid artery stenting that
      incorporates the principle of flow reversal for neuroprotection. The technique
      bypasses all of the anatomic limitations of transfemoral access and simplifies
      the application of flow reversal, which is one of the safest neuroprotection
      techniques. The purpose of this review is to describe our method of transcervical
      carotid artery stenting, review the accumulating outcomes data, and discuss the
      clinical advantages of and indications for this increasingly popular technique.

PMID- 17038295
TI  - Training in carotid artery stenting: do carotid simulation systems really help?
AB  - Virtual reality (VR) simulations have long been used for training in aviation and
      other professions. High-fidelity endovascular procedure simulators are now
      available, providing procedure simulations with real-time interactions; two
      dimensional graphic displays of angiographic anatomy; mechanical interfaces with
      guidewires, sheaths, and catheters that provide some degree of haptic feedback;
      modeling of physiologic and pharmacology responses; and other features.
      Simulators have been incorporated into training programs for physicians learning
      carotid artery stenting (CAS). For the first time, US Food and Drug
      Administration approval of a new device (CAS systems) has included a requirement
      for physician training that incorporates the use of VR simulators. Early
      experience has shown that simulation is well accepted by trainees, performance on
      simulators improves with training and practice, and simulation prior to first
      performing endovascular procedures can improve clinical performance. Specific to
      CAS, the value of education programs using simulators appears to be tangible as
      trained but inexperienced CAS operators have clinical results comparable to those
      of physicians with extensive CAS experience.

PMID- 17038296
TI  - Aneurysm sac pressure measurement with a pressure sensor in endovascular aortic
      aneurysm repair.
AB  - Aortic endograft surveillance is a necessity for the lifetime of a patient owing
      to the risk of endoleaks and device complications. The current standard of care
      for surveillance is radiologic imaging. The most commonly used modality is
      computed tomographic angiography. Magnetic resonance angiography and
      ultrasonography have also been used as surveillance tools. These imaging
      techniques have risks and limitations, and alternative surveillance tools are
      being investigated. Remote pressure sensing is a promising technology that can
      provide adjunctive support to the current imaging modalities. The technology is
      applicable to both abdominal and thoracic endograft implantation and
      surveillance. It has recently gained clearance from the US Food and Drug
      Administration for acute aneurysm exclusion during an abdominal endograft
      insertion. As more data are accumulated, it may be possible for remote pressure
      sensing to replace current imaging techniques as the sole modality for endograft
      surveillance.

PMID- 17038297
TI  - Percutaneous thoracic and abdominal aortic aneurysm repair: techniques and
      outcomes.
AB  - Endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) has become a
      widely accepted treatment modality. The conventional approach of an EVAR involves
      bilateral groin incisions to expose the femoral arteries followed by introducer
      sheath placement, which is typically performed with the use of general or
      epidural anesthesia. As technology trends toward less invasive methods and sheath
      sizes become smaller, the use of a total percutaneous approach to endovascular
      repair of aortic pathology is becoming more common. In this review, we present a
      brief history of percutaneous closure devices for common femoral artery access,
      factors important in patient selection, the technique of performing a
      percutaneous EVAR procedure, early and late complications, and overall outcomes
      of percutaneous approaches for the endovascular treatment of aortic pathology.

PMID- 17038298
TI  - Management of aortic aneurysms and dissections with the Zenith TX2 stent graft.
AB  - Endovascular repair of thoracic aortic aneurysms offers a less invasive
      alternative to conventional surgery, similar to its counterpart in the abdominal
      aorta. Although its long-term durability and outcome remain relatively unknown,
      published midterm results from clinical trials suggest comparable rates of
      aneurysm-related mortality and significant reductions in early morbidity compared
      with open repair. The Zenith TX2 stent graft (Cook Endovascular, Bloomington, IN)
      is an investigational endovascular device that is designed to treat aneurysms and
      other degenerative pathologies of the thoracic aorta. At the time of this
      writing, it is nearing completion of its pivotal trial. Clinical experience with
      this device is limited to countries outside the United States and to sites
      participating in the clinical trials. The purpose of this article is to provide a
      description of the Zenith TX2 device and its application in the repair of
      thoracic aortic aneurysms and dissections.

PMID- 17038299
TI  - Indications and results with cryoplasty in the treatment of infrainguinal
      arterial occlusive disease.
AB  - Percutaneous transluminal angioplasty of the superficial femoral and popliteal
      arteries has been an accepted therapy for short focal stenosis. Elastic recoil
      and flow-limiting dissection have limited the durability of angioplasty,
      especially in long lesions and total occlusions. Cryoplasty couples cold therapy
      with angioplasty to induce mechanical and biologic effects to reduce elastic
      recoil and potentially to reduce restenosis. The mechanical and biologic
      mechanisms of this therapy are discussed. The results of cryoplasty for
      femoropopliteal lesions from a single-center series and a multicenter registry
      are reviewed. Cryoplasty appears to improve patency over conventional angioplasty
      and to reduce the need for bailout stenting in femoropopliteal stenoses and
      occlusions < 10 cm in length. Cryoplasty appears to be promising to treat
      critical limb ischemia in patients with tibial disease.

PMID- 17038300
TI  - Endovascular treatment of popliteal artery aneurysms.
AB  - Popliteal artery aneurysms are relatively uncommon but potentially limb
      threatening lesions that can thrombose or cause distal embolization.
      Identification of these aneurysms, especially in patients with abdominal aortic
      aneurysms, is imperative, and prophylactic treatment with either surgical
      exclusion and bypass or endoluminal stent grafting is critical to prevent these
      poor outcomes. Endovascular approaches currently using the Viabahn stent graft
      offer several advantages, including a minimally invasive approach, fewer
      perioperative complications, and a faster recovery. This must be balanced with a
      potentially higher failure rate or requirement for reintervention, although
      contemporary series report comparable short-term outcomes. We present our
      approach to the evaluation and diagnosis of popliteal aneurysms, the technical
      aspects of endovascular popliteal aneurysm repair, and a representative case
      study.

PMID- 17038301
TI  - Utility of retrievable vena cava filters and mechanical thrombectomy in the
      endovascular management of acute deep venous thrombosis.
AB  - Endovascular interventions of symptomatic deep venous thrombosis (DVT) using
      various therapeutic modalities, such as thrombolysis, mechanical thrombectomy,
      and inferior vena cava (IVC) filter placement, have received increased focus
      owing in part to advances in catheter-based interventional technologies. Although
      systemic anticoagulation remains the primary treatment modality in DVT, catheter
      based interventions can provide rapid removal of large thrombus burden and
      possibly preserve venous valvular function in patients with symptomatic DVT. This
      article reviews current endovascular treatment strategies for acute DVT.
      Specifically, the utility of mechanical thrombectomy along with various temporary
      IVC filters in the setting of DVT is examined. Lastly, an illustrative case of
      acute DVT that was treated with endovascular intervention with IVC filter
      placement is presented.

PMID- 17038302
TI  - Infrainguinal arterial intervention: is there a role for an atherectomy device?
AB  - Excision of atheromatous plaque is an attractive option for the minimally
      invasive treatment of peripheral arterial disease. Approved for use in 2003, the
      SilverHawk Plaque Exicison System (FoxHollow Technologies, Redwood City, CA) is a
      catheter-based plaque excision device allowing percutaneous removal of
      atheromatous material. This device represents the most recent generation of
      atherectomy tools. Overall experience with plaque debulking in the peripheral
      arteries spans almost two decades, and understanding of the technique continues
      to evolve. This article reviews the technology, current practices, and data on
      plaque excision.

PMID- 17038305
TI  - Citalopram and suicidality in adult major depression and anxiety disorders.
AB  - The suicide-related data on citalopram from controlled clinical trials in
      depression and anxiety disorders were analysed. Safety data from placebo
      controlled and relapse prevention citalopram trials in depression/major
      depressive disorder (MDD) and anxiety were searched for specific events relating
      to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item
      10, suicidal thoughts, on the Montgomery-Asberg Depression Rating Scale [MADRS])
      were also analysed. In the clinical trial database, the number of adverse events
      (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during
      the first 2 weeks of treatment and during the full treatment period, with no
      statistically significant differences between citalopram and placebo. There was
      one fatal suicide during treatment (after 12 weeks of double-blind treatment in a
      relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%;
      rate: 0.010) and none on placebo. Citalopram was significantly more efficacious
      than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item
      10). There was no indication from this review of clinical trial data that
      citalopram may increase the risk of suicide in patients with MDD or anxiety.
      However, the patients in these clinical trials represent a selected group, as
      those patients with a significant risk of suicide were excluded at trial onset.

PMID- 17038304
TI  - Biotin uptake by rabbit corneal epithelial cells: role of sodium-dependent
      multivitamin transporter (SMVT).
AB  - PURPOSE: The objective of this research was to investigate the presence of sodium
      dependent multivitamin transporter (SMVT) on rabbit corneal epithelial cells.
      METHODS: Primary cultured rabbit corneal epithelial cells (rPCECs)and freshly
      excised rabbit corneas were used for characterization of biotin uptake and
      transport, respectively. Reverse transcription-polymerase chain reaction (RT-PCR)
      was performed to confirm the molecular identity of SMVT. Liquid
      chromatography/tandem mass spectrometry (LC-MS/MS) analysis was performed to
      examine the presence of biotin in rabbit tears. RESULTS: Uptake of biotin by
      rPCECs was found to be time and concentration dependent with Km of 32.52 microM
      and Vmax of 10.43 pmol min- 1 mg protein- 1. Biotin was significantly inhibited
      in the presence of pantothenic acid and lipoic acid. Biotin uptake was found to
      be energy and Na+ dependent but H+ and Cl- independent. The uptake was inhibited
      by valeric acid in a concentration-dependent manner but not much affected in the
      presence of biotin methyl ester and biocytin with no free carboxyl group.
      Modulators of both PKC- and PKA-mediated pathways had no effect on biotin uptake,
      but calcium-calmodulin inhibitor significantly inhibited its uptake. Sodium
      dependent multivitamin transporter was identified by RT-PCR in rPCECs. Transport
      experiments across the rabbit corneas revealed the functional localization of
      SMVT on the apical side of the cornea, and thereby corroborating with in vitro
      results with cultured corneal cells. Finally, LC-MS/MS analysis showed the
      presence of biotin in rabbit tears. CONCLUSIONS: Results obtained from both in
      vitro and exvivo studies suggest the possible role of SMVT expressed on corneal
      epithelial cells for the uptake of biotin, which co-transports pantothenic acid
      and lipoic acid. Further, the presence of biotin in tears suggests the
      physiological significance of this transporter in rabbit corneal epithelium.

PMID- 17038306
TI  - Image-guided system with miniature robot for precise positioning and targeting in
      keyhole neurosurgery.
AB  - This paper describes a novel image-guided system for precise automatic targeting
      in minimally invasive keyhole neurosurgery. The system consists of the MARS
      miniature robot fitted with a mechanical guide for needle, probe or catheter
      insertion. Intraoperatively, the robot is directly affixed to a head clamp or to
      the patient's skull. It automatically positions itself with respect to predefined
      targets in a preoperative CT/MRI image following an anatomical registration with
      an intraoperative 3D surface scan of the patient's facial features and
      registration jig. We present the system architecture, surgical protocol, custom
      hardware (targeting and registration jig), and software modules (preoperative
      planning, intraoperative execution, 3D surface scan processing, and three-way
      registration). We also describe a prototype implementation of the system and in
      vitro registration experiments. Our results indicate a system-wide target
      registration error of 1.7 mm (standard deviation = 0.7 mm), which is close to the
      required 1.0-1.5 mm clinical accuracy in many keyhole neurosurgical procedures.

PMID- 17038307
TI  - Synergistic effects of the SAPK/JNK and the proteasome pathway on glial
      fibrillary acidic protein (GFAP) accumulation in Alexander disease.
AB  - Protein aggregates in astrocytes that contain glial fibrillary acidic protein
      (GFAP), small heat shock proteins, and ubiquitinated proteins are termed
      Rosenthal fibers and characterize Alexander disease, a leukodystrophy caused by
      heterozygous mutations in GFAP. The mechanisms responsible for the massive
      accumulation of GFAP in Alexander disease remain unclear. In this study, we show
      that overexpression of both wild type and R239C mutant human GFAP led to
      cytoplasmic inclusions. GFAP accumulation also led to a decrease of proteasome
      activity and an activation of the MLK2-JNK pathway. In turn, the expression of
      activated mixed lineage kinases (MLKs) induced JNK activation and increased GFAP
      accumulation, whereas blocking the JNK pathway decreased GFAP accumulation.
      Activated MLK also inhibited proteasome function. A direct inhibition of
      proteasome function pharmacologically further activated JNK. Our data suggest a
      synergistic interplay between the proteasome and the SAPK/JNK pathway in the
      context of GFAP accumulation. Feedback interactions among GFAP accumulation,
      SAPK/JNK activation, and proteasomal hypofunction cooperate to produce further
      protein accumulation and cellular stress responses.

PMID- 17038308
TI  - Heparan sulfate analysis from diabetic rat glomeruli.
AB  - One of the major complicating factors in insulin-dependent diabetes mellitus is
      nephropathy. Several investigators have linked heparan sulfate (HS) alterations
      in the glomerular basement membrane (GBM) with albuminuria as a marker of
      abnormal blood filtration and the subsequent progression to renal failure. In
      this study, we examined the fine structure of HS in the glomerulus and the GBM
      isolated from the kidneys of rats injected with streptozotocin. Using fluorophore
      assisted carbohydrate electrophoresis, we obtained disaccharide composition
      analyses for HS. In a time course study, we observed that normal rat HS isolated
      from the GBM becomes more N-sulfated as the glomeruli mature over a period of 8
      weeks. Diabetic rats injected with streptozotocin at the beginning of this period
      showed a reversal of this trend. Using a graded sieve technique, we found that
      two different sizes of glomeruli could be isolated from the rat kidneys and that
      there was a significant difference in the HS disaccharide content between these
      two pools of glomeruli. Only the larger sized glomeruli had less N-sulfation of
      HS as a result of insulin-dependent diabetes mellitus. This change in the fine
      structure of HS was localized to the GBM and was not associated with cell surface
      HS. We also generated oligosaccharides of HS that portray fine structural
      alterations in the diabetic rats indicative of a loss of the sulfation of N
      acetylglucosamine.

PMID- 17038309
TI  - Evolutionary and functional conservation of the DNA non-homologous end-joining
      protein, XLF/Cernunnos.
AB  - Non-homologous end-joining is a major pathway of DNA double-strand break repair
      in mammalian cells, deficiency in which confers radiosensitivity and immune
      deficiency at the whole organism level. A core protein complex comprising the
      Ku70/80 heterodimer together with a complex between DNA ligase IV and XRCC4 is
      conserved throughout eukaryotes and assembles at double-strand breaks to mediate
      ligation of broken DNA ends. In Saccharomyces cerevisiae an additional NHEJ
      protein, Nej1p, physically interacts with the ligase IV complex and is required
      in vivo for ligation of DNA double-strand breaks. Recent studies with cells
      derived from radiosensitive and immune-deficient patients have identified the
      human protein, XLF (also named Cernunnos), as a crucial NHEJ protein. Here we
      show that XLF and Nej1p are members of the same protein superfamily and that this
      family has members in diverse eukaryotes. Indeed, we show that a member of this
      family encoded by a previously uncharacterized open-reading frame in the
      Schizosaccharomyces pombe genome is required for NHEJ in this organism.
      Furthermore, our data reveal that XLF family proteins can bind to DNA and
      directly interact with the ligase IV-XRCC4 complex to promote DSB ligation. We
      therefore conclude that XLF family proteins interact with the ligase IV-XRCC4
      complex to constitute the evolutionarily conserved enzymatic core of the NHEJ
      machinery.

PMID- 17038310
TI  - Structural and membrane binding analysis of the Phox homology domain of
      phosphoinositide 3-kinase-C2alpha.
AB  - Phox homology (PX) domains, which have been identified in a variety of proteins
      involved in cell signaling and membrane trafficking, have been shown to interact
      with phosphoinositides (PIs) with different affinities and specificities. To
      elucidate the structural origin of diverse PI specificities of PX domains, we
      determined the crystal structure of the PX domain from phosphoinositide 3-kinase
      C2alpha (PI3K-C2alpha), which binds phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P(2)). To delineate the mechanism by which this PX domain interacts
      with membranes, we measured the membrane binding of the wild type domain and
      mutants by surface plasmon resonance and monolayer techniques. This PX domain
      contains a signature PI-binding site that is optimized for PtdIns(4,5)P(2)
      binding. The membrane binding of the PX domain is initiated by nonspecific
      electrostatic interactions followed by the membrane penetration of hydrophobic
      residues. Membrane penetration is specifically enhanced by PtdIns(4,5)P(2).
      Furthermore, the PX domain displayed significantly higher PtdIns(4,5)P(2)
      membrane affinity and specificity when compared with the PI3K-C2alpha C2 domain,
      demonstrating that high affinity PtdIns(4,5)P(2) binding was facilitated by the
      PX domain in full-length PI3K-C2alpha. Together, these studies provide new
      structural insight into the diverse PI specificities of PX domains and elucidate
      the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)
      containing membranes and thereby mediates the membrane recruitment of PI3K
      C2alpha.

PMID- 17038311
TI  - Proline-rich motifs in the parathyroid hormone (PTH)/PTH-related protein receptor
      C terminus mediate scaffolding of c-Src with beta-arrestin2 for ERK1/2
      activation.
AB  - Parathyroid hormone (PTH) stimulates ERK1/2 through both G-protein signaling and
      beta-arrestin2-mediated internalization. Beta-arrestin may serve as a scaffold
      for c-Src. However, the molecular mechanisms for ERK1/2 activation by PTH remain
      unclear. By using a targeted mutagenesis approach, we investigated the PTH/PTH
      related protein receptor (PTH1R) structural determinants for ERK1/2 activation
      and transcriptional activity in HEK-293 cells. First, ERK1/2 activation was
      inhibited by PTH1R mutations that specifically abrogate G(q)-protein kinase C
      signaling without a decrease in cAMP-protein kinase A. Second, PTH1R C-terminal
      mutations and/or deletions that prevent interaction with beta-arrestin inhibited
      ERK1/2 activation. Similar results were obtained in HEK-293 cells co-expressing
      wild-type PTH1R and a dominant-negative beta-arrestin2. Third, the c-Src
      inhibitor PP2 and a kinase-dead c-SrcK295M mutant co-expressed with wild-type
      PTH1R both inhibited ERK1/2 activation. Furthermore, c-Src co-precipitated with
      both PTH1R and beta-arrestin2 in response to PTH. Deleting the PTH1R-proximal C
      terminus abolished these interactions. However, the need for receptor interaction
      with beta-arrestin to co-precipitate Src and activate ERK1/2 was obviated by
      expressing a constitutively active c-SrcY527A mutant, suggesting direct binding
      of activated Src to PTH1R. Subsequently, we identified and mutated to alanine
      four proline-rich motifs in the PTH1R distal C terminus, which resulted in loss
      of both c-Src and arrestin co-precipitation and significantly decreased ERK1/2
      activation. These data delineate the multiple PTH1R structural determinants for
      ERK1/2 activation and newly identify a unique mechanism involving proline-rich
      motifs in the receptor C terminus for reciprocal scaffolding of c-Src and beta
      arrestin2 with a class II G-protein-coupled receptor.

PMID- 17038312
TI  - Topology of the VirB4 C terminus in the Agrobacterium tumefaciens VirB/D4 type IV
      secretion system.
AB  - Gram-negative type IV secretion systems (T4SSs) transfer proteins and DNA to
      eukaryotic and/or prokaryotic recipients resulting in pathogenesis or conjugative
      DNA transfer. VirB4, one of the most conserved proteins in these systems, has
      both energetic and structural roles in substrate translocation. We previously
      predicted a structural model for the large C-terminal domain (residues 425-789)
      of VirB4 of Agrobacterium tumefaciens. Here we have defined a homology-based
      structural model for Agrobacterium VirB11. Both VirB4 and VirB11 models predict
      hexameric oligomers. Yeast two-hybrid interactions define peptides in the C
      terminus of VirB4 and the N terminus of VirB11 that interact with each other.
      These interactions were mapped onto the homology models to predict direct
      interactions between the hexameric interfaces of VirB4 and VirB11 such that the
      VirB4 C terminus stacks above VirB11 in the periplasm. In support of this,
      fractionation and Western blotting show that the VirB4 C terminus is localized to
      the membrane and periplasm rather than the cytoplasm of cells. Additional high
      resolution yeast two-hybrid results demonstrate interactions between the C
      terminus of VirB4 and the periplasmic portions of VirB1, VirB8, and VirB10.
      Genetic studies reveal dominant negative interactions and thus function of the
      VirB4 C terminus in vivo. The above data are integrated with the existing body of
      literature to propose a structural, periplasmic role for the C-terminal half of
      the Agrobacterium VirB4 protein.

PMID- 17038313
TI  - Protein kinase C-dependent enhancement of activity of rat brain NCKX2
      heterologously expressed in HEK293 cells.
AB  - Different members of the Na+/Ca2++K+ exchanger (NCKX) family are present in
      distinct brain regions, suggesting that they may have cell-specific functions.
      Many neuronal channels and transporters are regulated via phosphorylation.
      Regulation of the rat brain NCKXs by protein kinases, however, has not been
      described. Here, we report an increase in NCKX2 activity in response to protein
      kinase C (PKC) activation. Outward current of NCKX2 heterologously expressed in
      HEK293 cells was enhanced by beta-phorbol dibutyrate (PDBu), whereas PDBu had
      little effect on activity of NCKX3 or NCKX4. The PDBu-induced enhancement (PIE)
      of NCKX2 activity was abolished by PKC inhibitors and significantly reduced when
      the dominant negative mutant of PKCepsilon (K437R) was overexpressed. Moreover,
      PDBu accelerated the decay rate of the Ca2+ transient at the calyx of Held, where
      NCKX is the major Ca2+-clearance mechanism. Intracellular perfusion with alkaline
      phosphatase completely inhibited PIE. Consistently, beta-phorbol myristate
      acetate (PMA), but not 4alpha-PMA, induced a 3-fold stimulation of 32P
      incorporation into NCKX2 expressed in HEK293 cells. To investigate the sites
      involved, PIE of wild-type NCKX2 was compared with mutant NCKX2 in which the
      three putative PKC consensus sites were replaced with alanine, either
      individually or in combination. Double-site mutation involving Thr-476
      (T166A/T476A and T476A/S504A) disrupted PIE, whereas single mutation of Thr-166,
      Thr-476, or Ser-504 or the double mutant T166A/S504A failed to completely prevent
      PIE. These findings suggest that PKC-mediated activation of NCKX2 is sensitive to
      mutation of multiple PKC consensus sites via a mechanism that may involve several
      phosphorylation events.

PMID- 17038314
TI  - SNARE status regulates tether recruitment and function in homotypic COPII vesicle
      fusion.
AB  - In mammals, coat complex II (COPII)-coated transport vesicles deliver secretory
      cargo to vesicular tubular clusters (VTCs) that facilitate cargo sorting and
      transport to the Golgi. We documented in vitro tethering and SNARE-dependent
      homotypic fusion of endoplasmic reticulum-derived COPII transport vesicles to
      form larger cargo containers characteristic of VTCs ( Xu, D., and Hay, J. C.
      (2004) J. Cell Biol. 167, 997-1003). COPII vesicles thus appear to contain all
      necessary components for homotypic tethering and fusion, providing a pathway for
      de novo VTC biogenesis. Here we demonstrate that antibodies against the
      endoplasmic reticulum/Golgi SNARE Syntaxin 5 inhibit COPII vesicle homotypic
      tethering as well as fusion, implying an unanticipated role for SNAREs upstream
      of fusion. Inhibition of SNARE complex access and/or disassembly with dominant
      negative alpha-soluble NSF attachment protein (SNAP) also inhibited tethering,
      implicating SNARE status as a critical determinant in COPII vesicle tethering.
      The tethering-defective vesicles generated in the presence of dominant-negative
      alpha-SNAP specifically lacked the Rab1 effectors p115 and GM130 but not other
      peripheral membrane proteins. Furthermore, Rab effectors, including p115, were
      shown to be required for homotypic COPII vesicle tethering. Thus, our results
      demonstrate a requirement for SNARE-dependent tether recruitment and function in
      COPII vesicle fusion. We anticipate that recruitment of tether molecules by an
      upstream SNARE signal ensures that tethering events are initiated only at focal
      sites containing appropriately poised fusion machinery.

PMID- 17038315
TI  - Inhibition of Escherichia coli heat-labile enterotoxin B subunit pentamer (EtxB5)
      assembly in vitro using monoclonal antibodies.
AB  - Heat-labile enterotoxin (Etx) produced by certain strains of Escherichia coli is
      a major virulence factor related to cholera toxin. Both are hexameric proteins
      comprising one A-subunit and five B-subunits. The pentameric B-subunit of E. coli
      has a high affinity for G(M1)-ganglioside receptors on gut epithelial cells and
      is directly responsible for toxin entry. The pentameric B-subunit (EtxB(5)) is an
      exceptionally stable protein, being able to maintain its quaternary structure
      over a wide pH range (2.0- 11.0). However, little is known about the formation of
      the pentameric structure (EtxB(5)) from newly synthesized B-subunit monomers
      (EtxB(1)). We previously described and characterized a mAb (LDS47) that was shown
      to be highly specific for an N-terminal decapeptide region of EtxB(1) (Amin, T.,
      Larkins, A., James, R. F. L., and Hirst, T. R. (1995) J. Biol. Chem. 270, 20143
      20150). Here we also describe a mAb (LDS16) with exquisite specificity for
      pentameric EtxB. In this study, we have used these two mAbs, in combination, to
      probe the in vitro assembly of EtxB(5) from EtxB(1). EtxB pentamers disassemble
      in highly acidic conditions, giving rise to monomeric B-subunits that can
      reassemble if placed in buffers of neutral pH. Using this in vitro assembly
      model, it was found that at a molar ratio of 1:1; LDS47:EtxB, 50% of reassembly
      was inhibited, and that this inhibition increased to 90% at a ratio of 2:1. These
      results infer that the N-terminal decapeptide region (APQSITELCS) defined by the
      LDS47 antibody is crucial for competent pentameric B-subunit assembly and
      stabilization.

PMID- 17038316
TI  - Regulation of anterograde transport of alpha2-adrenergic receptors by the N
      termini at multiple intracellular compartments.
AB  - The studies on the intrinsic structural determinants for export trafficking of G
      protein-coupled receptors (GPCRs) have been mainly focused on the C termini of
      the receptors. In this report we determined the role of the extracellular N
      termini of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the anterograde
      transport from the endoplasmic reticulum (ER) through the Golgi to the cell
      surface. The N-terminal-truncated alpha(2B)-AR mutant is completely unable to
      target to the cell surface. A single Met-6 residue is essential for the export of
      alpha(2B)-AR from the ER, likely through modulating correct alpha(2B)-AR folding
      in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini
      of all alpha(2)-AR subtypes, is required for the exit of alpha(2A)-AR and
      alpha(2B)-AR from the Golgi apparatus, thus representing a novel Tyr-based motif
      modulating GPCR transport at the Golgi level. These data provide the first
      evidence indicating an essential role of the N termini of GPCRs in the export
      from distinct intracellular compartments along the secretory pathway.

PMID- 17038317
TI  - Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas.
AB  - We previously showed that activation of the small GTPase Cdc42 promotes breast
      cell migration on a collagen matrix. Here we further define the signaling
      pathways that drive this response and show that Cdc42-mediated migration relies
      on the adaptor molecule p130(Cas). Activated Cdc42 enhanced p130(Cas)
      phosphorylation and its binding to Crk. Cdc42-driven migration and p130(Cas)
      phosphorylation were dependent on the Cdc42 effector Ack1 (activated Cdc42
      associated kinase). Ack1 formed a signaling complex that also included Cdc42,
      p130(Cas), and Crk, formation of which was regulated by collagen stimulation. The
      interaction between Ack1 and p130(Cas) occurred through their respective SH3
      domains, while the substrate domain of p130(Cas) was the major site of Ack1
      dependent phosphorylation. Signaling through this complex is functionally
      relevant, because treatment with either p130(Cas) or Ack1 siRNA blocked Cdc42
      induced migration. These results suggest that Cdc42 exerts its effects on cell
      migration in part through its effector Ack1, which regulates p130(Cas) signaling.

PMID- 17038318
TI  - A Chinese hamster ovarian cell line imports cholesterol by high density
      lipoprotein degradation.
AB  - Plasma high density lipoprotein (HDL) is inversely associated with the
      development of atherosclerosis. HDL exerts its atheroprotective role through
      involvement in reverse cholesterol transport in which HDL is loaded with
      cholesterol at the periphery and transports its lipid load back to the liver for
      disposal. In this pathway, HDL is not completely dismantled but only transfers
      its lipids to the cell. Here we present evidence that a Chinese hamster ovarian
      cell line (CHO7) adapted to grow in lipoprotein-deficient media degrades HDL and
      concomitantly internalizes HDL-derived cholesterol. Delivery of HDL cholesterol
      to the cell was demonstrated by a down-regulation of cholesterol biosynthesis, an
      increase in total cellular cholesterol content and by stimulation of cholesterol
      esterification after HDL treatment. This HDL degradation pathway is distinct from
      the low density lipoprotein (LDL) receptor pathway but also degrades LDL. 25
      Hydroxycholesterol, a potent inhibitor of the LDL receptor pathway, down
      regulated LDL degradation in CHO7 cells only in part and did not down-regulate
      HDL degradation. Dextran sulfate released HDL bound to the cell surface of CHO7
      cells, and heparin treatment released protein(s) contributing to HDL degradation.
      The involvement of heparan sulfate proteoglycans and lipases in this HDL
      degradation was further tested by two inhibitors genistein and
      tetrahydrolipstatin. Both blocked HDL degradation significantly. Thus, we
      demonstrate that CHO7 cells degrade HDL and LDL to supply themselves with
      cholesterol via a novel degradation pathway. Interestingly, HDL degradation with
      similar properties was also observed in a human placental cell line.

PMID- 17038319
TI  - Fragmented hyaluronan induces transcriptional up-regulation of the multidrug
      resistance-1 gene in CD4+ T cells.
AB  - P-glycoprotein, encoded by the multidrug resistance (MDR)-1 gene, expels various
      drugs from cells resulting in multidrug resistance. We found previously that
      interleukin-2, a lymphocyte-activation cytokine, induces P-glycoprotein
      expression on lymphocytes. Lymphocyte activation involves adhesion with the
      extracellular matrix, such as hyaluronan, through adhesion molecules on
      lymphocytes. We investigated the transcriptional regulation of MDR-1 in
      lymphocytes by fragmented hyaluronan. Fragmented hyaluronan (especially the 6.9
      kDa form), not native high molecular hyaluronan, induced translocation of YB-1, a
      specific transcriptional factor for MDR-1, from the cytoplasm into the nucleus
      and resulted in the transcription of MDR-1 and the expression of P-glycoprotein
      on lymphocytes in a dose-dependent manner. Transfection of YB-1 antisense
      oligonucleotides inhibited P-glycoprotein expression induced by fragmented
      hyaluronan. The fragmented hyaluronan induced significant P-glycoprotein
      expression on only activated CD4+ T cells, which highly expressed CD69, and
      resulted in excretion of intracellular dexamethasone added in vitro. Cyclosporin
      A, a competitive P-glycoprotein inhibitor, restored intracellular dexamethasone
      levels in CD4+ T cells. Anti-CD44 monoclonal antibody (Hermes-1) inhibited
      fragmented hyaluronan-induced YB-1 activation and P-glycoprotein expression in
      CD4+ T cells. We provide the first evidence that binding of fragmented hyaluronan
      to CD44 induces YB-1 activation followed by P-glycoprotein expression in
      accordance with activation of CD4+ T cells. Our findings imply that CD4+ T cell
      activation by fragmented hyaluronan, induced by characteristic extracellular
      matrix changes in inflammation, tumors, and other conditions, results in P
      glycoprotein-mediated multidrug resistance.

PMID- 17038320
TI  - A three-dimensional model of human organic anion transporter 1: aromatic amino
      acids required for substrate transport.
AB  - Organic anion transporters (OATs) play a critical role in the handling of
      endogenous and exogenous organic anions by excretory and barrier tissues. Little
      is known about the OAT three-dimensional structure or substrate/protein
      interactions involved in transport. In this investigation, a theoretical three
      dimensional model was generated for human OAT1 (hOAT1) based on fold recognition
      to the crystal structure of the glycerol 3-phosphate transporter (GlpT) from
      Escherichia coli. GlpT and hOAT1 share several sequence motifs as major
      facilitator superfamily members. The structural hOAT1 model shows that helices 5,
      7, 8, 10, and 11 surround an electronegative putative active site ( approximately
      830A(3)). The site opens to the cytoplasm and is surrounded by three residues not
      previously examined for function (Tyr(230) (domain 5) and Lys(431) and Phe(438)
      (domain 10)). Effects of these residues on p-aminohippurate (PAH) and cidofovir
      transport were assessed by point mutations in a Xenopus oocyte expression system.
      Membrane protein expression was severely limited for the Y230A mutant. For the
      K431A and F438A mutants, [(3)H]PAH uptake was less than 30% of wild-type hOAT1
      uptake after protein expression correction. Reduced V(max) values for the F438A
      mutant confirmed lower protein expression. In addition, the F438A mutant
      exhibited an increased affinity for cidofovir but was not significantly different
      for PAH. Differences in handling of PAH and cidofovir were also observed for the
      Y230F mutant. Little uptake was determined for cidofovir, whereas PAH uptake was
      similar to wild-type hOAT1. Therefore, the hOAT1 structural model has identified
      two new residues, Tyr(230) and Phe(438), which are important for
      substrate/protein interactions.

PMID- 17038321
TI  - The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+
      channels.
AB  - The putative hinge point revealed by the crystal structure of the MthK potassium
      channel is a glycine residue that is conserved in many ion channels. In high
      voltage-activated (HVA) Ca(V) channels, the mid-S6 glycine residue is only
      present in IS6 and IIS6, corresponding to G422 and G770 in Ca(V)1.2. Two
      additional glycine residues are found in the distal portion of IS6 (Gly(432) and
      Gly(436) in Ca(V)1.2) to form a triglycine motif unique to HVA Ca(V) channels.
      Lethal arrhythmias are associated with mutations of glycine residues in the human
      L-type Ca(2+) channel. Hence, we undertook a mutational analysis to investigate
      the role of S6 glycine residues in channel gating. In Ca(V)1.2, alpha-helix
      breaking proline mutants (G422P and G432P) as well as the double G422A/G432A
      channel did not produce functional channels. The macroscopic inactivation
      kinetics were significantly decreased with Ca(V)1.2 wild type > G770A > G422A
      congruent with G436A >> G432A (from the fastest to the slowest). Mutations at
      position Gly(432) produced mostly nonfunctional mutants. Macroscopic inactivation
      kinetics were markedly reduced by mutations of Gly(436) to Ala, Pro, Tyr, Glu,
      Arg, His, Lys, or Asp residues with stronger effects obtained with charged and
      polar residues. Mutations within the distal GX(3)G residues blunted Ca(2+)
      dependent inactivation kinetics and prevented the increased voltage-dependent
      inactivation kinetics brought by positively charged residues in the I-II linker.
      In Ca(V)2.3, mutation of the distal glycine Gly(352) impacted significantly on
      the inactivation gating. Altogether, these data highlight the role of the GX(3)G
      motif in the voltage-dependent activation and inactivation gating of HVA Ca(V)
      channels with the distal glycine residue being mostly involved in the
      inactivation gating.

PMID- 17038322
TI  - Flap endonuclease disengages Dna2 helicase/nuclease from Okazaki fragment flaps.
AB  - Okazaki fragments contain an initiator RNA/DNA primer that must be removed before
      the fragments are joined. In eukaryotes, the primer region is raised into a flap
      by the strand displacement activity of DNA polymerase delta. The Dna2
      helicase/nuclease and then flap endonuclease 1 (FEN1) are proposed to act
      sequentially in flap removal. Dna2 and FEN1 both employ a tracking mechanism to
      enter the flap 5' end and move toward the base for cleavage. In the current
      model, Dna2 must enter first, but FEN1 makes the final cut at the flap base,
      raising the issue of how FEN1 passes the Dna2. To address this, nuclease-inactive
      Dna2 was incubated with a DNA flap substrate and found to bind with high
      affinity. FEN1 was then added, and surprisingly, there was little inhibition of
      FEN1 cleavage activity. FEN1 was later shown, by gel shift analysis, to remove
      the wild type Dna2 from the flap. RNA can be cleaved by FEN1 but not by Dna2. Pre
      bound wild type Dna2 was shown to bind an RNA flap but not inhibit subsequent
      FEN1 cleavage. These results indicate that there is a novel interaction between
      the two proteins in which FEN1 disengages the Dna2 tracking mechanism. This
      interaction is consistent with the idea that the two proteins have evolved a
      special ability to cooperate in Okazaki fragment processing.

PMID- 17038323
TI  - Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+
      channel in macrophages.
AB  - Voltage-dependent K(+) (Kv) currents in macrophages are mainly mediated by Kv1.3,
      but biophysical properties indicate that the channel composition could be
      different from that of T-lymphocytes. K(+) currents in mouse bone marrow-derived
      and Raw-264.7 macrophages are sensitive to Kv1.3 blockers, but unlike T-cells,
      macrophages express Kv1.5. Because Shaker subunits (Kv1) may form
      heterotetrameric complexes, we investigated whether Kv1.5 has a function in Kv
      currents in macrophages. Kv1.3 and Kv1.5 co-localize at the membrane, and half
      activation voltages and pharmacology indicate that K(+) currents may be accounted
      for by various Kv complexes in macrophages. Co-expression of Kv1.3 and Kv1.5 in
      human embryonic kidney 293 cells showed that the presence of Kv1.5 leads to a
      positive shift in K(+) current half-activation voltages and that, like Kv1.3,
      Kv1.3/Kv1.5 heteromers are sensitive to r-margatoxin. In addition, both proteins
      co-immunoprecipitate and co-localize. Fluorescence resonance energy transfer
      studies further demonstrated that Kv1.5 and Kv1.3 form heterotetramers.
      Electrophysiological and pharmacological studies of different ratios of Kv1.3 and
      Kv1.5 co-expressed in Xenopus oocytes suggest that various hybrids might be
      responsible for K(+) currents in macrophages. Tumor necrosis factor-alpha-induced
      activation of macrophages increased Kv1.3 with no changes in Kv.1.5, which is
      consistent with a hyperpolarized shift in half-activation voltage and a lower
      IC(50) for margatoxin. Taken together, our results demonstrate that Kv1.5 co
      associates with Kv1.3, generating functional heterotetramers in macrophages.
      Changes in the oligomeric composition of functional Kv channels would give rise
      to different biophysical and pharmacological properties, which could determine
      specific cellular responses.

PMID- 17038324
TI  - Murine leukemia virus regulates alternative splicing through sequences upstream
      of the 5' splice site.
AB  - Alternative splicing of the primary transcript plays a key role in retroviral
      gene expression. In contrast to all known mechanisms that mediate alternative
      splicing in retroviruses, we found that in murine leukemia virus, distinct
      elements located upstream of the 5' splice site either inhibited or activated
      splicing of the genomic RNA. Detailed analysis of the first untranslated exon
      showed that the primer binding site (PBS) activates splicing, whereas flanking
      sequences either downstream or upstream of the PBS are inhibitory. This new
      function of the PBS was independent of its orientation and primer binding but
      associated with a particular destabilizing role in a proposed secondary
      structure. On the contrary, all sequences surrounding the PBS that are involved
      in stem formation of the first exon were found to suppress splicing. Targeted
      mutations that destabilized the central stem and compensatory mutations of the
      counter strand clearly validated the concept that murine leukemia virus
      attenuates its 5' splice site by forming an inhibitory stem-loop in its first
      exon. Importantly, this mode of splice regulation was conserved in a complete
      proviral clone. Some of the mutants that increase splicing revealed an opposite
      effect on translation, implying that the first exon also regulates this process.
      Together, these findings suggest that sequences upstream of the 5' splice site
      play an important role in splice regulation of simple retroviruses, directly or
      indirectly attenuating the efficiency of splicing.

PMID- 17038325
TI  - Combined leptin actions on adipose tissue and hypothalamus are required to
      deplete adipocyte fat in lean rats: implications for obesity treatment.
AB  - Intense hyperleptinemia completely depletes adipocyte fat of normal rats within
      14 days. To determine the mechanism, epididymal fat pads from normal wild-type
      (+/+) and obese (fa/fa) Zucker Diabetic Fatty (ZDF) donor rats were transplanted
      into normal +/+ and fa/fa ZDF recipients. Hyperleptinemia induced by adenovirus
      leptin administration depleted all fat from native fat pads and from fat
      transplants from +/+ donors but not from transplants from ZDF(fa/fa) donors with
      defective leptin receptors. In both native and transplanted +/+ fat pads, large
      numbers of mitochondria were apparent, and genes involved in fatty acid oxidation
      were up-regulated. However, +/+ fat pads transplanted into fa/fa recipients did
      not respond to hyperleptinemia, suggesting lack of an essential leptin-stimulated
      cohormone(s). In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and
      both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct
      and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia
      are involved in depletion of adipocyte fat.

PMID- 17038326
TI  - Cyclic GMP-dependent protein kinase Ialpha attenuates necrosis and apoptosis
      following ischemia/reoxygenation in adult cardiomyocyte.
AB  - Cyclic GMP-dependent protein kinases protein kinase G (PKG) Ialpha and PKGIbeta
      are major mediators of cGMP signaling in the cardiovascular system. PKGIalpha is
      present in the heart, although its role in protection against
      ischemia/reperfusion injury is not known. We investigated the direct effect of
      PKGIalpha against necrosis and apoptosis following simulated ischemia (SI) and
      reoxygenation (RO) in cardiomyocytes. Adult rat cardiomyocytes were infected with
      adenoviral vectors containing hPKGIalpha or catalytically inactive mutant
      hPKGIalphaK390A. After 24 h, the cells were subjected to 90 min of SI and 2 h RO
      for necrosis (trypan blue exclusion and lactate dehydrogenase release) or 18 h RO
      for apoptosis studies. To evaluate the role of K(ATP) channels, subgroups of
      cells were treated with 5-hydroxydecanoate (100 microm), HMR1098 (30 microm), or
      glibenclamide (50 microm), the respective blockers of mitochondrial, sarcolemmal,
      or both types of K(ATP) channels prior to SI. The necrosis observed in 33.7 +/-
      1.6% of total myocytes in the SI-RO control group was reduced to 18.6 +/- 0.8% by
      PKGIalpha (mean +/- S.E., n = 7, p < 0.001). The apoptosis observed in 17.9 +/-
      1.3% of total myocytes in the SI-RO control group was reduced to 6.0 +/- 0.6% by
      PKGIalpha (mean +/- S.E., n = 7, p < 0.001). In addition, PKGIalpha inhibited the
      activation of caspase-3 after SI-RO in myocytes. Myocytes infected with the
      inactive PKGIalphaK390A mutant showed no protection. PKGIalpha enhanced
      phosphorylation of Akt, ERK1/2, and JNK, increased Bcl-2, inducible nitric-oxide
      synthase, endothelial nitric-oxide synthase, and decreased Bax expression. 5
      Hydroxydecanoate and glibenclamide abolished PKGIalpha-mediated protection
      against necrosis and apoptosis. However, HMR1098, had no effect. A scavenger of
      reactive oxygen species, as well as inhibitors of phosphatidylinositol 3-kinase,
      ERK, JNK1, and NOS, also blocked PKGIalpha-mediated protection against necrosis
      and apoptosis. These results show that opening of mitochondrial K(ATP) channels
      and generation of reactive oxygen species, in association with phosphorylation of
      Akt, ERK, and JNK, and increased expression of NOS and Bcl-2, play an essential
      role in the protective effect of PKGIalpha.

PMID- 17038327
TI  - The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is
      protected from degradation by interacting with the deubiquitylating enzyme
      FAM/USP9X.
AB  - Itch is a ubiquitin ligase that has been implicated in the regulation of a number
      of cellular processes. We previously have identified Itch as a binding partner
      for the endocytic protein Endophilin and found it to be localized to endosomes.
      Using affinity purification coupled to mass spectrometry, we have now identified
      the ubiquitin-protease FAM/USP9X as a binding partner of Itch. The association
      between Itch and FAM/USP9X was confirmed in vitro by glutathione S-transferase
      pulldown and in vivo through coimmunoprecipation. Itch and FAM partially
      colocalize in COS-7 cells at the trans-Golgi network and in peripheral vesicles.
      We mapped the FAM-binding domain on Itch to the WW domains, a region known to be
      involved in substrate recognition. However, transient overexpression of FAM/USP9X
      resulted in the deubiquitylation of Itch. Moreover, we show that Itch auto
      ubiquitylation leads to its degradation in the proteasome. By examining the
      amounts of Itch and FAM in various cell lines and rat tissues, a positive
      correlation was found in the expression of both proteins. This observation
      suggests that the levels of FAM expression could have an influence on Itch in
      cells. Experimental decrease in FAM levels by RNA interference leads to a
      significant reduction in intracellular levels of endogenous Itch, which can be
      prevented by treatment with the proteasome inhibitor lactacystin. Accordingly,
      overexpression of FAM/USP9X resulted in a marked increase in endogenous Itch
      levels. These results demonstrate an intriguing interplay between a ubiquitin
      ligase and a ubiquitin protease, based on direct interaction between the two
      proteins.

PMID- 17038328
TI  - Protein kinase CK2 is inhibited by human nucleolar phosphoprotein p140 in an
      inositol hexakisphosphate-dependent manner.
AB  - Protein kinase CK2 is a ubiquitous protein kinase that can phosphorylate various
      proteins involved in central cellular processes, such as signal transduction,
      cell division, and proliferation. We have shown that the human nucleolar
      phosphoprotein p140 (hNopp140) is able to regulate the catalytic activity of CK2.
      Unphosphorylated hNopp140 and phospho-hNopp140 bind to the regulatory and
      catalytic subunits of CK2, respectively, and the interaction between hNopp140 and
      CK2 was prevented by inositol hexakisphosphate (InsP(6)). Phosphorylation of
      alpha-casein, genimin, or human phosphatidylcholine transfer protein-like protein
      by CK2 was inhibited by hNopp140, and InsP(6) recovered the suppressed activity
      of CK2 by hNopp140. These observations indicated that hNopp140 serves as a
      negative regulator of CK2 and that InsP(6) stimulates the activity of CK2 by
      blocking the interaction between hNopp140 and CK2.

PMID- 17038329
TI  - Audit-based education to reduce suboptimal management of cholesterol in primary
      care: a before and after study.
AB  - BACKGROUND: Statins are recommended for the secondary prevention of
      cardiovascular disease, although they are often used in suboptimal doses and some
      patients may not receive lipid-lowering therapy. The Primary Care Data Quality
      (PCDQ) programme is an audit-based educational intervention. OBJECTIVE: To report
      the PCDQ programme's effect on the cholesterol management in cardiovascular
      disease. Subjects and methods Anonymized general practice data from 99 practices;
      5% (n = 29 915) had cardiovascular diagnoses. RESULTS: Mean cholesterol fell from
      4.75 to 4.64 mmol l(-1); patients achieving cholesterol target (< 5 mmol l(-1))
      rose from 45.3 to 53.2%. Coronary heart disease patients achieved better control
      (mean 4.57 mmol l(-1)) than those with stroke (4.87 mmol l(-1)) or peripheral
      vascular disease (4.93 mmol l(-1)). Statin prescribing increased from 57.5 to
      62.7%. Patients with diabetes [odds ratio (OR) 2.06, 95% confidence interval (95%
      CI) 1.91-2.21], prior myocardial infarction (MI) (OR 1.93, 95% CI 1.80-2.07),
      revascularization (OR 1.52, 95% CI 1.33-1.73) and smokers (OR 1.31, 95% CI 1.23
      1.39) were more likely to receive statins, whereas people aged 75+ (OR 0.48, 95%
      CI 0.45-0.50), females (OR 0.90, 95% CI 0.86-0.94) and non-CHD-diagnosed (OR
      0.36, 95% CI 0.34-0.38) were less likely. CONCLUSIONS: Diagnostic coding and
      number of patients who had their cholesterol measured and treated increased.
      There was no significant change in dosage used or inequity between the different
      groups prescribed statins.

PMID- 17038330
TI  - Evolutionarily conserved and non-conserved retrovirus restriction activities of
      artiodactyl APOBEC3F proteins.
AB  - The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection
      through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host
      defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here,
      we report an APOBEC3F-like, double deaminase domain protein from three
      artiodactyls: cattle, pigs and sheep. Like their human counterparts, APOBEC3F and
      APOBEC3G, the artiodactyl APOBEC3F proteins are DNA cytosine deaminases that
      locate predominantly to the cytosol and can inhibit the replication of HIV-1 and
      MLV. Retrovirus restriction is attributable to deaminase-dependent and 
      independent mechanisms, as deaminase-defective mutants retain significant anti
      retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl
      APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which
      elicits a broader dinucleotide deamination preference, and they are resistant to
      HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular
      localization and retrovirus restriction activities are conserved in mammals,
      whereas active site location, local mutational preferences and Vif susceptibility
      are not. Together, these studies indicate that some properties of the mammal
      specific, APOBEC3-dependent retroelement restriction system are necessary and
      conserved, but others are simultaneously modular and highly adaptable.

PMID- 17038331
TI  - Codeine-binding RNA aptamers and rapid determination of their binding constants
      using a direct coupling surface plasmon resonance assay.
AB  - RNA aptamers that bind the opium alkaloid codeine were generated using an
      iterative in vitro selection process. The binding properties of these aptamers,
      including equilibrium and kinetic rate constants, were determined through a
      rapid, high-throughput approach using surface plasmon resonance (SPR) analysis to
      measure real-time binding. The approach involves direct coupling of the target
      small molecule onto a sensor chip without utilization of a carrier protein. Two
      highest binding aptamer sequences, FC5 and FC45 with K(d) values of 2.50 and 4.00
      microM, respectively, were extensively studied. Corresponding mini-aptamers for
      FC5 and FC45 were subsequently identified through the described direct coupling
      Biacore assays. These assays were also employed to confirm the proposed secondary
      structures of the mini-aptamers. Both aptamers exhibit high specificity to
      codeine over morphine, which differs from codeine by a methyl group. Finally, the
      direct coupling method was demonstrated to eliminate potential non-specific
      interactions that may be associated with indirect coupling methods in which
      protein linkers are commonly employed. Therefore, in addition to presenting the
      first RNA aptamers to a subclass of benzylisoquinoline alkaloid molecules, this
      work highlights a method for characterizing small molecule aptamers that is more
      robust, precise, rapid and high-throughput than other commonly employed
      techniques.

PMID- 17038332
TI  - Rational design and rapid screening of antisense oligonucleotides for prokaryotic
      gene modulation.
AB  - Antisense oligodeoxynucleotides (oligos) are widely used for functional studies
      of both prokaryotic and eukaryotic genes. However, the identification of
      effective target sites is a major issue in antisense applications. Here, we study
      a number of thermodynamic and structural parameters that may affect the potency
      of antisense inhibition. We develop a cell-free assay for rapid oligo screening.
      This assay is used for measuring the expression of Escherichia coli lacZ, the
      antisense target for experimental testing and validation. Based on a training set
      of 18 oligos, we found that structural accessibility predicted by local folding
      of the target mRNA is the most important predictor for antisense activity. This
      finding was further confirmed by a direct validation study. In this study, a set
      of 10 oligos was designed to target accessible sites, and another set of 10
      oligos was selected to target inaccessible sites. Seven of the 10 oligos for
      accessible sites were found to be effective (>50% inhibition), but none of the
      oligos for inaccessible sites was effective. The difference in the antisense
      activity between the two sets of oligos was statistically significant. We also
      found that the predictability of antisense activity by target accessibility was
      greatly improved for oligos targeted to the regions upstream of the end of the
      active domain for beta-galactosidase, the protein encoded by lacZ. The
      combination of the structure-based antisense design and extension of the lacZ
      assay to include gene fusions will be applicable to high-throughput gene
      functional screening, and to the identification of new drug targets in pathogenic
      microbes. Design tools are available through the Sfold Web server at
      http://sfold.wadsworth.org.

PMID- 17038333
TI  - Indirect readout: detection of optimized subsequences and calculation of relative
      binding affinities using different DNA elastic potentials.
AB  - Essential biological processes require that proteins bind to a set of specific
      DNA sites with tuned relative affinities. We focus on the indirect readout
      mechanism and discuss its theoretical description in relation to the present
      understanding of DNA elasticity on the rigid base pair level. Combining existing
      parametrizations of elastic potentials for DNA, we derive elastic free energies
      directly related to competitive binding experiments, and propose a
      computationally inexpensive local marker for elastically optimized subsequences
      in protein-DNA co-crystals. We test our approach in an application to the
      bacteriophage 434 repressor. In agreement with known results we find that
      indirect readout dominates at the central, non-contacted bases of the binding
      site. Elastic optimization involves all deformation modes and is mainly due to
      the adapted equilibrium structure of the operator, while sequence-dependent
      elasticity plays a minor role. These qualitative observations are robust with
      respect to current parametrization uncertainties. Predictions for relative
      affinities mediated by indirect readout depend sensitively on the chosen
      parametrization. Their quantitative comparison with experimental data allows for
      a critical evaluation of DNA elastic potentials and of the correspondence between
      crystal and solution structures. The software written for the presented analysis
      is included as Supplementary Data.

PMID- 17038334
TI  - Troubleshooting coupled in vitro transcription-translation system derived from
      Escherichia coli cells: synthesis of high-yield fully active proteins.
AB  - Cell-free coupled transcription-translation systems with bacterial lysates are
      widely used to synthesize recombinant proteins in amounts of several mg per ml.
      By using reporter green fluorescence protein (GFP) we demonstrate that proteins
      are synthesized with an unsatisfyingly low-active fraction of (50 +/- 20)%. One
      reason is probably the T7 polymerase used, being up to eight times faster than
      the intrinsic transcriptase and thus breaking the coupling between transcription
      and translation in bacterial systems. The active fraction of the synthesized
      protein was improved by using either a slower T7 transcriptase mutant or lowering
      the incubation temperature to 20 degrees C. A drop of protein synthesis observed
      after 7 h incubation time was not due to a shortage of nucleotide triphosphates,
      but rather to a shortage of amino acids. Accordingly, a second addition of amino
      acids after 10 h during an incubation at 20 degrees C led to synthesis of up to 4
      mg/ml of GFP with virtually 100% activity.

PMID- 17038335
TI  - Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: a novel
      class of bioactive molecules.
AB  - Short oligonucleotides below 8-10 nt in length adopt relatively simple
      structures. Accordingly, they represent interesting and so far unexplored lead
      compounds as molecular tools and, potentially, for drug development as a rational
      improvement of efficacy seem to be less complex than for other classes of longer
      oligomeric nucleic acid. As a 'proof of concept', we describe the highly specific
      binding of the hexanucleotide UCGUGU (Hex-S3) to human immunodeficiency virus
      type 1 (HIV-1) reverse transcriptase (RT) as a model target. Ultraviolet (UV)
      cross-linking studies and competition experiments with primer/template substrates
      and a RT-directed aptamer suggest site-specific binding of Hex-S3 to the large
      subunit (p66) of the viral enzyme. The affinity of 5.3 muM is related to
      hexanucleotide-specific suppression of HIV-1 replication in human cells by up to
      three orders of magnitude indicating that Hex-S3 exerts specific and biologically
      relevant activity. Experimental evidence described here further suggests a
      systematic hexamer array-based search for new tools for molecular biology and
      novel lead compounds in nucleic acid-based drug development.

PMID- 17038338
TI  - Measuring covariation in RNA alignments: physical realism improves information
      measures.
AB  - MOTIVATION: The importance of non-coding RNAs is becoming increasingly evident,
      and often the function of these molecules depends on the structure. It is common
      to use alignments of related RNA sequences to deduce the consensus secondary
      structure by detecting patterns of co-evolution. A central part of such an
      analysis is to measure covariation between two positions in an alignment. Here,
      we rank various measures ranging from simple mutual information to more advanced
      covariation measures. RESULTS: Mutual information is still used for secondary
      structure prediction, but the results of this study indicate which measures are
      useful. Incorporating more structural information by considering e.g. indels and
      stacking improves accuracy, suggesting that physically realistic measures yield
      improved predictions. This can be used to improve both current and future
      programs for secondary structure prediction. The best measure tested is the
      RNAalifold covariation measure modified to include stacking. AVAILABILITY:
      Scripts, data and supplementary material can be found at
      http://www.binf.ku.dk/Stinus_covariation

PMID- 17038336
TI  - The key DNA-binding residues in the C-terminal domain of Mycobacterium
      tuberculosis DNA gyrase A subunit (GyrA).
AB  - As only the type II topoisomerase is capable of introducing negative
      supercoiling, DNA gyrase is involved in crucial cellular processes. Although the
      other domains of DNA gyrase are better understood, the mechanism of DNA binding
      by the C-terminal domain of the DNA gyrase A subunit (GyrA-CTD) is less clear.
      Here, we investigated the DNA-binding sites in the GyrA-CTD of Mycobacterium
      tuberculosis gyrase through site-directed mutagenesis. The results show that
      Y577, R691 and R745 are among the key DNA-binding residues in M.tuberculosis GyrA
      CTD, and that the third blade of the GyrA-CTD is the main DNA-binding region in
      M.tuberculosis DNA gyrase. The substitutions of Y577A, D669A, R691A, R745A and
      G729W led to the loss of supercoiling and relaxation activities, although they
      had a little effect on the drug-dependent DNA cleavage and decatenation
      activities, and had no effect on the ATPase activity. Taken together, these
      results showed that the GyrA-CTD is essential to DNA gyrase of M.tuberculosis,
      and promote the idea that the M.tuberculosis GyrA-CTD is a new potential target
      for drug design. It is the first time that the DNA-binding sites in GyrA-CTD have
      been identified.

PMID- 17038340
TI  - ssSNPer: identifying statistically similar SNPs to aid interpretation of genetic
      association studies.
AB  - ssSNPer is a novel user-friendly web interface that provides easy determination
      of the number and location of untested HapMap SNPs, in the region surrounding a
      tested HapMap SNP, which are statistically similar and would thus produce
      comparable and perhaps more significant association results. Identification of
      ssSNPs can have crucial implications for the interpretation of the initial
      association results and the design of follow-up studies. AVAILABILITY:
      http://fraser.qimr.edu.au/general/daleN/ssSNPer/

PMID- 17038339
TI  - A supervised hidden markov model framework for efficiently segmenting tiling
      array data in transcriptional and chIP-chip experiments: systematically
      incorporating validated biological knowledge.
AB  - MOTIVATION: Large-scale tiling array experiments are becoming increasingly common
      in genomics. In particular, the ENCODE project requires the consistent
      segmentation of many different tiling array datasets into 'active regions' (e.g.
      finding transfrags from transcriptional data and putative binding sites from ChIP
      chip experiments). Previously, such segmentation was done in an unsupervised
      fashion mainly based on characteristics of the signal distribution in the tiling
      array data itself. Here we propose a supervised framework for doing this. It has
      the advantage of explicitly incorporating validated biological knowledge into the
      model and allowing for formal training and testing. METHODOLOGY: In particular,
      we use a hidden Markov model (HMM) framework, which is capable of explicitly
      modeling the dependency between neighboring probes and whose extended version
      (the generalized HMM) also allows explicit description of state duration density.
      We introduce a formal definition of the tiling-array analysis problem, and
      explain how we can use this to describe sampling small genomic regions for
      experimental validation to build up a gold-standard set for training and testing.
      We then describe various ideal and practical sampling strategies (e.g. maximizing
      signal entropy within a selected region versus using gene annotation or known
      promoters as positives for transcription or ChIP-chip data, respectively).
      RESULTS: For the practical sampling and training strategies, we show how the size
      and noise in the validated training data affects the performance of an HMM
      applied to the ENCODE transcriptional and ChIP-chip experiments. In particular,
      we show that the HMM framework is able to efficiently process tiling array data
      as well as or better than previous approaches. For the idealized sampling
      strategies, we show how we can assess their performance in a simulation framework
      and how a maximum entropy approach, which samples sub-regions with very different
      signal intensities, gives the maximally performing gold-standard. This latter
      result has strong implications for the optimum way medium-scale validation
      experiments should be carried out to verify the results of the genome-scale
      tiling array experiments.

PMID- 17038341
TI  - NMPP: a user-customized NimbleGen microarray data processing pipeline.
AB  - NMPP package is a bundle of user-customized tools based on established algorithms
      and methods to process self-designed NimbleGen microarray data. It features a
      command-line-based integrative processing procedure that comprises five major
      functional components, namely the raw microarray data parsing and integrating
      module, the array spatial effect smoothing and visualization module, the probe
      level multi-array normalization module, the gene expression intensity
      summarization module and the gene expression status inference module.
      AVAILABILITY: http://plantgenomics.biology.yale.edu/nmpp

PMID- 17038342
TI  - Maximum likelihood inference of imprinting and allele-specific expression from
      EST data.
AB  - MOTIVATION: In a diploid organism the proportion of transcripts that are produced
      from the two parental alleles can differ substantially due, for example to
      epigenetic modification that causes complete or partial silencing of one parental
      allele or to cis acting polymorphisms that affect transcriptional regulation.
      Counts of SNP alleles derived from EST sequences have been used to identify both
      novel candidates for genomic imprinting as well as examples of genes with allelic
      differences in expression. RESULTS: We have developed a set of statistical models
      in a maximum likelihood framework that can make highly efficient use of public
      transcript data to identify genes with unequal representation of alternative
      alleles in cDNA libraries. We modelled both imprinting and allele-specific
      expression and applied the models to a large dataset of SNPs mapped to EST
      sequences. Using simulations, matched closely to real data, we demonstrate
      significantly improved performance over existing methods that have been applied
      to the same data. We further validated the power of this approach to detect
      imprinting using a set of known imprinted genes and inferred a set of candidate
      imprinted genes, several of which are in close proximity to known imprinted
      genes. We report evidence that there are undiscovered imprinted genes in known
      imprinted regions. Overall, more than half of the genes for which the most data
      are available show some evidence of allele-specific expression. AVAILABILITY:
      Software is available from the authors on request.

PMID- 17038343
TI  - THOR: targeted high-throughput ortholog reconstructor.
AB  - Low-coverage genomes (LCGs) are becoming an increasingly important source of data
      for phylogenetic studies. However, assembly of these genomes is time consuming,
      difficult and lags behind sequence generation. THOR is a fast, stringent
      application for targeted reconstruction of sequence orthologs in unassembled
      LCGs. Using a 4x coverage set of mouse whole-genome sequence reads, THOR could
      partially or completely reconstruct 416/1000 human promoter ortholog regions in
      approximately 7.3 min/promoter. THOR's reconstruction rate improves markedly with
      both higher-coverage, and less divergent target species.

PMID- 17038344
TI  - Parameter estimation using Simulated Annealing for S-system models of biochemical
      networks.
AB  - MOTIVATION: High-throughput technologies now allow the acquisition of biological
      data, such as comprehensive biochemical time-courses at unprecedented rates.
      These temporal profiles carry topological and kinetic information regarding the
      biochemical network from which they were drawn. Retrieving this information will
      require systematic application of both experimental and computational methods.
      RESULTS: S-systems are non-linear mathematical approximative models based on the
      power-law formalism. They provide a general framework for the simulation of
      integrated biological systems exhibiting complex dynamics, such as genetic
      circuits, signal transduction and metabolic networks. We describe how the
      heuristic optimization technique simulated annealing (SA) can be effectively used
      for estimating the parameters of S-systems from time-course biochemical data. We
      demonstrate our methods using three artificial networks designed to simulate
      different network topologies and behavior. We then end with an application to a
      real biochemical network by creating a working model for the cadBA system in
      Escherichia coli. AVAILABILITY: The source code written in C++ is available at
      http://www.engg.upd.edu.ph/~naval/bioinformcode.html. All the necessary programs
      including the required compiler are described in a document archived with the
      source code. SUPPLEMENTARY INFORMATION: Supplementary material is available at
      Bioinformatics online.

PMID- 17038345
TI  - Repseek, a tool to retrieve approximate repeats from large DNA sequences.
AB  - Chromosomes or other long DNA sequences contain many highly similar repeated sub
      sequences. While there are efficient methods for detecting strict repeats or
      detecting already characterized repeats, there is no software available for
      detecting approximate repeats in large DNA sequences allowing for weighted
      substitutions and indels in a coherent statistical framework. Here, we present an
      implementation of a two-steps method (seed detection followed by their extension)
      that detects those approximate repeats. Our method is computationally efficient
      enough to handle large sequences and is flexible enough to account for
      influencing factors, such as sequence-composition biases both at the seed
      detection and alignment levels. AVAILABILITY:
      http://wwwabi.snv.jussieu.fr/public/RepSeek/

PMID- 17038346
TI  - Supporting the SBML layout extension.
AB  - MOTIVATION: Researchers studying large or complex biochemical networks would
      benefit from the ability to automatically create lucid visualizations and store
      them in a portable and widely accepted format. SUMMARY: Two modules,
      SBMLSupportLayout and SBWAutoLayout, support reading, creating, manipulating and
      writing layout information for biochemical models. SBMLSupportLayout can read,
      update, add and render model layout information. SBWAutoLayout can automatically
      layout models, graphically manipulate model layout and generate layout
      information for models without layout information. AVAILABILITY:
      SBMLSupportLayout and SBWAutoLayout are distributed with the Systems Biology
      Workbench (SBW), which can be downloaded from http://www.sys-bio.org.
      Additionally, their visualization and layout capabilities are available online at
      http://www.sys-bio.org/Layout. Both modules run on Win32, Linux and the Mac OS X
      version is forthcoming.

PMID- 17038347
TI  - Cell++--simulating biochemical pathways.
AB  - MOTIVATION: With the generation of a wealth of information, detailing cellular
      components, their functions and interactions, there is a growing need for the
      development of new computational tools capable of interpreting these data within
      spatial and dynamic contexts. Here, we introduce Cell++, a novel stochastic
      simulation environment with the capacity to study a wide variety of biochemical
      processes within a spatial context. RESULTS: Focusing on three case studies, we
      highlight the potential impact of spatial organization in the evolution and
      engineering of signaling and metabolic pathways. In addition to altering
      signaling and metabolic efficiency, simulations also demonstrated features
      consistent with the phenomenon of metabolic channeling. AVAILABILITY: Cell++ is
      licensed under the GNU general public license (GPL) and has been successfully
      implemented under Linux and IRIX operating systems. Source code together with a
      simple tutorial is available at http://www.compsysbio.org/CellSim/.

PMID- 17038348
TI  - Genetic characterization of the dihydrofolate reductase gene of Pneumocystis
      jirovecii isolates from Portugal.
AB  - OBJECTIVES: The aim of the present study was to evaluate the genetic variation of
      Pneumocystis jirovecii dihydrofolate reductase (DHFR) gene in an
      immunocompromised Portuguese population and to investigate the possible
      association between DHFR genotypes and P. jirovecii pneumonia (PcP) prophylaxis
      with co-trimoxazole. METHODS: One hundred and thirty-eight P. jirovecii isolates
      were submitted to DHFR genetic characterization by PCR and sequencing. RESULTS:
      In the studied population, 72.7% of the patients presented sequences identical to
      the wild-type sequence of the P. jirovecii DHFR gene and 27.3% presented point
      substitutions. A total of nine substitution sites were identified; four
      synonymous substitutions at nucleotide positions 201, 272, 312 and 381 were
      detected in 31 patients. Five non-synonymous substitutions were observed, leading
      to the DHFR mutations Leu-13-->Ser, Asn-23-->Ser, Ser-31-->Phe, Met-52-->Leu and
      Ala-67-->Val. With the exception of the polymorphism at position 312 and the
      mutation at codon 52, all polymorphisms were reported in this study for the first
      time. CONCLUSIONS: Our results suggest that DHFR gene polymorphisms are frequent
      in the Portuguese immunocompromised population but do not seem to be associated
      with PcP prophylaxis failure (P = 0.748 and P = 0.730).

PMID- 17038349
TI  - Is inducibility of atrial fibrillation after radio frequency ablation really a
      relevant prognostic factor?
AB  - AIMS: The study was intended to assess the prognostic value of inducibility of
      atrial fibrillation (AF) after radio frequency ablation. METHODS AND RESULTS: Two
      hundred and thirty four patients with drug-resistant paroxysmal (n=165) or
      persistent AF (n=69) underwent either Lasso-guided segmental pulmonary vein
      isolation (n=83) or CARTO-guided left atrial circumferential ablation (n=151).
      After ablation, two attempts to induce AF (>1 min) by decremental coronary sinus
      stimulation were performed. Patients were followed for at least 6 months (median:
      12.7 months). At 6 months of follow-up, 67% of patients with paroxysmal and 48%
      of patients with persistent AF were AF-free. Inducibility of AF was a significant
      predictor of AF recurrence in univariate [hazard ratio (HR)=2.32, P<0.001] and
      multivariable (HR=2.19, P<0.001) Cox regression analyses. The prognostic value of
      inducibility was present in both patients with paroxysmal (HR=2.38, P=0.001) and
      persistent AF (HR=1.91, P=0.034) and did not significantly differ between both
      ablation techniques. The sensitivity, specificity, positive, and negative
      predictive values of the AF induction test to predict the 6-month ablation
      outcome were 46.7, 75, 53.8, and 69.2%, respectively. CONCLUSION: Inducibility of
      AF after ablation is a significant predictor of recurrent AF. However, owing to
      the low diagnostic accuracy of the AF induction test, non-inducibility does not
      qualify as reliable procedural endpoint.

PMID- 17038350
TI  - Devices in heart failure: building up the evidence.

PMID- 17038351
TI  - Coronary Buerger's disease with a peripheral arterial aneurysm.

PMID- 17038352
TI  - Enhanced Fc-dependent cellular cytotoxicity of Fc fusion proteins derived from
      TNF receptor II and LFA-3 by fucose removal from Asn-linked oligosaccharides.
AB  - Fucose removal from complex-type oligosaccharide of human IgGs results in a major
      enhancement of Fc-dependent cellular cytotoxicity. The aim of this study was to
      determine the effect of fucose removal on the effector function of another class
      of clinically important molecules that can effect cellular cytotoxicity, Fc
      fusion proteins. The receptors chosen for study were TNF receptor II and LFA-3,
      both of which have therapeutic significance. The fucosylated versions of these
      fusion proteins were produced in unmodified CHO cells, whereas the nonfucosylated
      counterparts were produced in CHO cells with alpha-1,6-fucosyltransferase, an
      enzyme required for fucosylation, knocked-out. Whilst binding activity of TNFRII
      Fc and LFA-3-Fc were unchanged by fucose-removal, nonfucosylated Fc fusion
      proteins exhibited significantly higher Fc receptor gammaIIIa-binding and
      increased Fc-mediated cytotoxicity on target cells compared to fucosylated
      counterparts. Notably, in case of TNFRII-Fc, only the nonfucosylated protein
      exhibited potent Fc dependent cytotoxicity to transmembrane TNF-alpha expressing
      cells. These results prove that enhancement of Fc dependent cellular cytotoxicity
      by fucose-removal is effective in not only whole IgG but also Fc fusion proteins,
      and thus widens the potential of Fc-fusion proteins as therapeutic candidates.

PMID- 17038403
TI  - Improved characterisation of the HPA PADC neutron personal dosemeter.
AB  - The fast neutron energy dependence of response of the HPA PADC neutron personal
      dosemeter has been measured from 144 keV to 19 MeV using monoenergetic neutron
      fields. Below 144 keV the relative energy and angle dependence of response have
      been determined using MCNP-4C2. New data from the SIGMA field at Cadarache,
      France, have been used to determine the appropriate scaling factor for the
      calculated response to thermal and intermediate energy neutrons. These newly
      determined response characteristics of the dosemeter are discussed with respect
      to its performance in the EVIDOS workplace field irradiations.

PMID- 17038404
TI  - Treating voxel geometries in radiation protection dosimetry with a patched
      version of the Monte Carlo codes MCNP and MCNPX.
AB  - The question of Monte Carlo simulation of radiation transport in voxel geometries
      is addressed. Patched versions of the MCNP and MCNPX codes are developed aimed at
      transporting radiation both in the standard geometry mode and in the voxel
      geometry treatment. The patched code reads an unformatted FORTRAN file derived
      from DICOM format data and uses special subroutines to handle voxel-to-voxel
      radiation transport. The various phases of the development of the methodology are
      discussed together with the new input options. Examples are given of employment
      of the code in internal and external dosimetry and comparisons with results from
      other groups are reported.

PMID- 17038405
TI  - Identification of static exposure of standard dosimetric badge with
      thermoluminescent detectors.
AB  - There are three main methods used in individual monitoring: radiographic films,
      thermoluminescence (TL) and optically stimulated luminescence (OSL).
      Distinguishing between static (e.g. by leaving it accidentally or purposely in
      the radiation field) and dynamic exposures can be almost routinely performed for
      radiographic and OSL methods but is still unsolved for TL detectors. The main aim
      of this work is to develop a method for identifying static exposures of standard
      TL detectors at doses which are typical of radiation protection. For this
      purpose, a new TLD reader equipped with a CCD camera was developed to measure the
      two-dimensional signal map and not only the total light emitted (as is performed
      with standard photomultiplier-based TL readers). Standard MCP-N (LiF:Mg,Cu,P) TL
      pellets of 4.5 mm diameter and 0.9 mm thickness were installed in the standard
      Rados TL personal badges with special, non-uniform filters and exposed statically
      to 33 keV X-ray beams at three angles: 0 degrees, 30 degrees and 60 degrees. The
      detectors were readout in the CCD camera reader and 2-D images were collected.
      The analysis of these CCD images allows the identification of the static exposure
      cases and partly the angle of incidence at a dose level of 20 mSv.

PMID- 17038406
TI  - Progress report of the CR-39 neutron personal monitoring service at PSI.
AB  - At the Paul Scherrer Institute a personal neutron dosimetry system based on
      chemically etched CR-39 detectors and automatic track counting is in routine use
      since the beginning of 1998. The quality of the CR-39 detectors has always been a
      crucial aspect to maintain a trustable personal neutron dosimetry system. This
      paper summarises the 7 y experience in routine use. The effect of detector
      material defects which could lead to false positive neutron doses is described.
      The potentiality of improving the background statistics by extending the pre-etch
      time is investigated and involves as a drawback a quite lower sensitivity to
      thermal neutrons. Furthermore, the impact of small changes in the production
      process of the detectors on the response to fast and thermal neutrons is shown.
      For the personal dosimetry at CERN, a new dosimetry concept was launched by
      combining a CR-39 neutron dosemeter with a Direct-Ion Storage (DIS) dosemeter for
      photon and beta radiation. The usage period of the CR-39 dosemeters is prolonged
      now from 3 months up to 12 months. In this context, the long-term behaviour over
      1 y of the background track density and the response to Am-Be are described.

PMID- 17038407
TI  - Practical assessment of the display performance of radiology workstations.
AB  - The performance of 14 primary clinical display monitor workstations in use in the
      Radiology Department of a large acute NHS Trust was assessed using the methods
      and guidelines described by the American Association of Physicists in Medicine
      Task Group 18. Tests undertaken included the measurement of ambient light,
      display uniformity, luminance ratio, luminance response, maximum luminance and
      spatial resolution. Four display monitors failed to meet at least one of the
      test's guideline tolerances. In addition a number of display monitors were found
      to be operating at settings that might reduce their useful life span. These
      devices were either replaced or recalibrated by the installers, or were subject
      to local adjustment to ensure applicable standards were met. Consequently the
      study suggests that quality assurance testing of display monitors used for image
      reporting is necessary and valuable to ensure that images are viewed at an
      appropriate standard.

PMID- 17038408
TI  - An efficient method for calculating kinetic parameters in a dual-input single
      compartment model.
AB  - Quantitative measurement of hepatic perfusion has the potential to provide
      important information in the assessment and management of various liver diseases.
      The utility of hepatic perfusion characterization relies on the resolution of
      each component of its dual blood supply, i.e. the hepatic artery and portal vein.
      In this study, a linear equation was derived by integrating the differential
      equation describing the kinetic behaviour of contrast agent (CA) in a dual-input
      single-compartment model, from which the kinetic parameters can be easily
      obtained using the linear least-squares method. The usefulness of this method was
      investigated using computer simulations, in comparison with the non-linear least
      squares (NLSQ) method. This method calculated the kinetic parameters faster than
      the NLSQ method by a factor of approximately 10, with almost the same accuracy as
      the NLSQ method. This method will be useful for analysing the kinetic behaviour
      of CA in the unique liver environment, especially by generating the functional
      images of kinetic parameters.

PMID- 17038409
TI  - Usefulness of saline pushing in reduction of contrast material dose in abdominal
      CT: evaluation of time-density curve for the aorta, portal vein and liver.
AB  - The effects of saline pushing after contrast material injection were investigated
      as well as the possibility for this technique to reduce contrast material doses
      in liver CT examinations. 52 patients were divided randomly into three groups:
      100 ml of contrast material (300 mg I ml(-1)) only (A; n = 19), 100 ml of
      contrast material pushed with 50 ml of saline solution (B; n = 17), and 85 ml of
      contrast material pushed with 50 ml of saline solution (C; n = 16). Single-level
      images were obtained at the level of the main portal vein after the initiation of
      contrast material injection. There were no significant differences in the mean
      peak enhancement values (PE) and the mean time to peak enhancement values (TPE)
      of the aorta between the three groups. The mean PE of the portal vein in group B
      increased 21 HU over that in group A (p<0.05), and there was no significant
      difference between groups A and C. The mean PE of the liver in group B increased
      7 HU over that in group A (p<0.05), and there was no significant difference
      between groups A and C. The mean TPE of the portal vein was shorter by 4 s
      (p<0.05), and that of the liver was shorter by 5 s (p<0.05) in group C compared
      with those in group A. In conclusion, saline pushing increases the enhancement
      values of the portal vein and liver, and allows a contrast material dose
      reduction of 15 ml without decreasing hepatic and vascular enhancement at
      adequate scan timing.

PMID- 17038410
TI  - 16-slice CT: achievable effective doses of common protocols in comparison with
      recent CT dose surveys.
AB  - The aim of the study was to investigate achievable dose levels in 16-slice CT by
      evaluating CT dose indices (CTDI) and effective doses of dose-optimized protocols
      compared with 4-slice dose surveys. Normalized CTDI free in air and in 16 cm and
      32 cm diameter phantoms were measured on four different 16-slice CT scanners in
      the Netherlands. All collimation and tube potential settings were analysed.
      Volume CTDI was calculated for adult protocols for brain, chest, pulmonary
      angiography (CTPA), abdomen and biphasic liver CT. Effective doses were
      calculated first using volume CTDI with conversion factors and second from
      CTDIair values using the ImPACT dose calculator. Average results of the 16-slice
      scanners were correlated to results of dose surveys with predominantly 4-slice
      scanners. Statistical analysis was done with Student t-tests with a Bonferroni
      correction; therefore p < 0.017 was significant. The results of CTDIair and
      weighted CTDI were documented for all scanners. Effective doses averaged over
      four scanners for brain, chest, CTPA, abdomen and biphasic liver protocols were
      1.9+/-0.4, 3.8+/-0.4, 3.0+/-0.2, 7.2+/-0.9 and 10.2+/-1.3 mSv, respectively.
      Compared with dose surveys achievable effective doses were equal (p = 0.069) to
      significantly lower (p < 0.017) for chest and abdomen protocols. For 16-slice
      spiral brain CT there was a trend of equal doses compared with sequential brain
      CT in the dose surveys. Thus, with dose-optimized protocols 16-slice CT can
      achieve equal to lower effective doses in examinations of the chest and abdomen
      compared with 4-slice CT, while doses can remain stable in the brain.

PMID- 17038411
TI  - Metastatic carcinoma of the breast: the appearances of metastatic spread to the
      abdomen and pelvis as demonstrated by CT.
AB  - This review illustrates some CT appearances of metastatic breast cancer in the
      subdiaphragmatic abdomen and pelvis. Such manifestations are not uncommon in
      advanced disease and familiarity will enable confident diagnosis in patients at
      risk for metastatic disease.

PMID- 17038412
TI  - Combined therapy of transcatheter arterial chemoembolisation and three
      dimensional conformal radiotherapy for hepatocellular carcinoma.
AB  - To evaluate the toxicity and efficacy of combined therapy of three-dimensional
      conformal radiotherapy (3DCRT) and transcatheter arterial chemoembolisation
      (TACE) for hepatocellular carcinoma (HCC). 50 HCC patients treated by combined
      TACE and 3DCRT were selected from a patient database. Sequence of treatments was
      that TACE was performed first, followed by 3DCRT with an interval of about 4
      weeks between. TACE was administered by 5-Fu 500-600 mg m(-2), cis-platinum 30-40
      mg m(-2), epi-adriamycin 40-60 mg m(-2) mixed with iodized oil and Gelfoam
      embolisation. A median of two courses of TACE was given. 3DCRT was delivered by 4
      6 coplanar or non-coplanar fields. The mean tumour dose was 43.0+/-6.3 Gy by
      conventional fractionation (2 Gy per fraction, five fractions a week), and mean
      dose to normal liver, 19.1+/-6.3 Gy. Acute hepatic toxicities were notable in
      five patients (10%) with Common Toxicity Criteria (CTC) grade 1 in two cases and
      grade 3 in three patients, but all recovered eventually. Two patients developed
      radiation-induced liver disease (RILD) and died soon after the onset of RILD.
      Four patients had Radiation Therapy Oncology Group (RTOG) grade 1 acute
      gastrointestinal complication and one patient had acute gastrointestinal
      bleeding. Five patients experienced RTOG Grade 1 leukopenia and Grade 2 in five
      cases. Nine patients achieved have partial response, and 37 patients were in
      stable disease. Four patients were observed to have progressive disease. The
      overall survival rates at 1 year, 2 years and 3 years were 60%, 38% and 28%,
      respectively, with a median survival period of 17 months. Irradiation dose, T
      stage and hepatic cirrhosis were identified as independent predictors for overall
      survival by Cox proportional regression analysis. The 1 year, 2 years and 3 years
      local progression-free rates were 74%, 57% and 38%, and the 1 year, 2 years and 3
      years distant metastasis rates were 15%, 21% and 40%, respectively. The combined
      modality of TACE and 3DCRT was tolerable for the majority of HCC patients,
      resulted in good outcome and warrants for further prospective trial.

PMID- 17038413
TI  - Risk factors for induction of breast cancer by X-rays and their implications for
      breast screening.
AB  - In order to discuss the balance of benefit and radiation risk in a breast
      screening programme, it is necessary to have numerical values for the probability
      of breast cancer induction by X-rays, stratified by age. Various sets of such
      values have been used hitherto, mainly in relation to breast screening in the UK,
      both within the NHS Screening Programme and more generally for younger age
      groups. Further sets have recently been reported. These different sets of values
      are described and discussed, together with the effects of using additive or
      relative risk models, and the effect of using a dose and dose rate modifying
      factor (DDREF). Possible new radiation risk factors for breast cancer induction
      by X-rays, drawn from these sets, are identified. These are used to calculate
      fresh values of cancer detection/induction ratios, as an index of benefit/risk,
      for screening age women and for younger women with and without a family history
      of breast cancer.

PMID- 17038414
TI  - Temperament and pain reactivity predict health behavior seven years later.
AB  - OBJECTIVE: Minor illnesses and major diseases are affected by individual,
      environmental, and social factors. We sought to determine if children's
      temperament and pain reactivity (individual response styles) measured in
      kindergarten are related to future health behavior. METHODS: Seven-year follow-up
      measures of health behavior were gathered in 42 children (mean age M = 11 years)
      who participated in a previous study of pain reactivity and somatization. Current
      health behavior was compared with children's pain reactivity and temperament
      measured in kindergarten. RESULTS: Pain reactivity in kindergarten was associated
      with children's self-reports of somatization 7 years later, independent of their
      temperament. Temperament was related to children's self-reports of somatization
      and to maternal reports of health care utilization and psychosocial health
      status. CONCLUSIONS: Early response styles (i.e., heightened pain reactivity and
      difficulty adjusting) may indicate risk for increased health care utilization and
      poorer health and well-being later in childhood.

PMID- 17038415
TI  - Jellyfish responsible for Irukandji syndrome.

PMID- 17038417
TI  - Jellyfish responsible for Irukandji syndrome.

PMID- 17038418
TI  - Cardiovascular disease risk factor knowledge in young adults and 10-year change
      in risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA)
      Study.
AB  - This study's objective was assessment of cardiovascular disease (CVD) risk factor
      knowledge in young adults, its association with 10-year changes in risk factor
      levels, and variables related to risk factor knowledge. A total of 4,193 healthy
      persons (55% female, 48% Black; mean age=30 years) from four urban US communities
      were queried about risk factor knowledge in 1990-1991 and were reexamined in 2000
      2001. Of six risk factors considered (hypertension, hyperlipidemia, smoking,
      overweight, sedentary lifestyle, and unhealthy diet), participants mentioned a
      mean of two; more than 65% were not aware of any risk factors, and less than 35%
      recognized being overweight as a risk factor. After adjustment, variables
      associated with mentioning more than two CVD risk factors versus one or fewer
      were Black race (OR=0.52, 95% confidence interval (CI): 0.44, 0.61), having a
      high school education or less (OR=0.88, 95% CI: 0.80, 0.95), having one or two
      (vs. zero) risk factors (OR=1.27, 95% CI: 1.05, 1.53), and having three or more
      (vs. zero) risk factors (OR=1.79, 95% CI: 1.35, 2.38). More knowledge was
      marginally associated with less increase in body mass index 10 years later
      (p=0.06) but was unrelated to other risk factor changes. Knowledge of CVD risk
      factors was very low in these young adults but increased with the presence of
      risk factors. Knowledge alone did not predict 10-year changes in risk factors.

PMID- 17038419
TI  - The use of in vitro peptide binding profiles and in silico ligand-receptor
      interaction profiles to describe ligand-induced conformations of the retinoid X
      receptor alpha ligand-binding domain.
AB  - It is hypothesized that different ligand-induced conformational changes can
      explain the different interactions of nuclear receptors with regulatory proteins,
      resulting in specific biological activities. Understanding the mechanism of how
      ligands regulate cofactor interaction facilitates drug design. To investigate
      these ligand-induced conformational changes at the surface of proteins, we
      performed a time-resolved fluorescence resonance energy transfer assay with 52
      different cofactor peptides measuring the ligand-induced cofactor recruitment to
      the retinoid X receptor-alpha (RXRalpha) in the presence of 11 compounds.
      Simultaneously we analyzed the binding modes of these compounds by molecular
      docking. An automated method converted the complex three-dimensional data of
      ligand-protein interactions into two-dimensional fingerprints, the so-called
      ligand-receptor interaction profiles. For a subset of compounds the
      conformational changes at the surface, as measured by peptide recruitment,
      correlate well with the calculated binding modes, suggesting that clustering of
      ligand-receptor interaction profiles is a very useful tool to discriminate
      compounds that may induce different conformations and possibly different effects
      in a cellular environment. In addition, we successfully combined ligand-receptor
      interaction profiles and peptide recruitment data to reveal structural elements
      that are possibly involved in the ligand-induced conformations. Interestingly, we
      could predict a possible binding mode of LG100754, a homodimer antagonist that
      showed no effect on peptide recruitment. Finally, the extensive analysis of the
      peptide recruitment profiles provided novel insight in the potential cellular
      effect of the compound; for the first time, we showed that in addition to the
      induction of coactivator peptide binding, all well-known RXRalpha agonists also
      induce binding of corepressor peptides to RXRalpha.

PMID- 17038420
TI  - Perceptions of Maori deaf identity in New Zealand.
AB  - Following the reframing of "Deaf" as a cultural and linguistic identity, ethnic
      minority members of Deaf communities are increasingly exploring their plural
      identities in relation to Deaf and hearing communities of affiliation. This
      article examines Maori Deaf people's perceptions of identity, during a coinciding
      period of Tino Rangatiratanga (Maori cultural and political self-determination
      and empowerment)1 and the emergence of Deaf empowerment. Interviews with 10 Maori
      Deaf participants reveal experiences of enculturation into Maori and Deaf
      communities and how they negotiate identity in these contexts. Consistent with
      the model of contextual identity in Deaf minority individuals of Foster and
      Kinuthia (2003), participants expressed fluid identities, in which Maori and Deaf
      aspects are both central but foregrounded differently in their interactions with
      hearing Maori, Deaf Maori, and the wider Deaf community. This New Zealand case
      study illustrates how changing sociopolitical conditions affect Deaf minority
      individuals' opportunity to achieve and express identification with both Deaf
      world and family heritage cultures.

PMID- 17038421
TI  - Biogeographic evidence for selection on mitochondrial DNA in North Pacific
      walleye pollock Theragra chalcogramma.
AB  - Three major mitochondrial DNA (mtDNA) haplogroups were identified in 5 data sets
      for North Pacific and Bering Sea walleye pollock. The common haplogroup A showed
      mirror-image clines on both sides of the North Pacific with high frequencies in
      southern areas (P(A) > 0.84) and low frequencies in the Bering Sea (P(A) < 0.36).
      Two additional haplogroups showed complimentary, but weaker, clines in the
      opposite direction. These clines are unlikely to have arisen by chance during
      postglacial colonizations of coastal waters in the North Pacific and Bering Sea,
      and they do not appear to reflect isolation by distance. Contrary to these
      trends, pollock at the western end of the Aleutian Island Archipelago were
      genetically more similar to Asian than to North American pollock, a pattern
      likely reflecting postglacial colonization. Haplogroup F(ST) values for a given
      haplotype diversity were significantly larger than expected under the island
      model of migration and random drift, a result implicating natural selection.
      Frequencies of haplogroup A were highly correlated with sea surface temperature
      (r > 0.91), whereas frequencies of groups B and C showed negative correlations
      with temperature. Selection may be operating directly on mtDNA variability or may
      be mediated through cytonuclear interactions. This biogeographic evidence adds to
      a growing body of literature indicating that selection may play a greater role in
      sculpting mtDNA variability than previously thought.

PMID- 17038422
TI  - TRPV1 is a novel target for omega-3 polyunsaturated fatty acids.
AB  - Omega-3 (n-3) fatty acids are essential for proper neuronal function, and they
      possess prominent analgesic properties, yet their underlying signalling
      mechanisms are unclear. Here we show that n-3 fatty acids interact directly with
      TRPV1, an ion channel expressed in nociceptive neurones and brain. These fatty
      acids activate TRPV1 in a phosphorylation-dependent manner, enhance responses to
      extracellular protons, and displace binding of the ultrapotent TRPV1 ligand
      [3H]resiniferatoxin. In contrast to their agonistic properties, n-3 fatty acids
      competitively inhibit the responses of vanilloid agonists. These actions occur in
      mammalian cells in the physiological concentration range of 1-10 mum.
      Significantly, docosahexaenoic acid exhibits the greatest efficacy as an agonist,
      whereas eicosapentaenoic acid and linolenic acid are markedly more effective
      inhibitors. Similarly, eicosapentaenoic acid but not docosahexaenoic acid
      profoundly reduces capsaicin-evoked pain-related behaviour in mice. These effects
      are independent of alterations in membrane elasticity because the micelle-forming
      detergent Triton X-100 only minimally affects TRPV1 properties. Thus, n-3 fatty
      acids differentially regulate TRPV1 and this form of signalling may contribute to
      their biological effects. Further, these results suggest that dietary
      supplementation with selective n-3 fatty acids would be most beneficial for the
      treatment of pain.

PMID- 17038423
TI  - Postnatal changes in ventilation during normoxia and acute hypoxia in the rat:
      implication for a sensitive period.
AB  - Previously, we found heightened expression of inhibitory neurochemicals and
      depressed expression of excitatory neurochemicals with a sudden drop in metabolic
      activity around postnatal day (P) 12 in rat brainstem respiratory nuclei,
      suggesting that this period is a critical window during which respiratory control
      or regulation may be distinctly different. To test this hypothesis, the hypoxic
      ventilatory responses (HVR) to 10% oxygen were tested in rats every day from P0
      to P21. Our data indicate that (1) during normoxia (N), breathing frequency (f)
      increased with age, peaking at P13, followed by a gradual decline, whereas both
      tidal volume (V(T)) and minute ventilation (.V(E) ) significantly increased in
      the second postnatal week, followed by a progressive increase in V(T) and a
      relative plateau in .V(E); (2) during 5 min of hypoxia (H), .V(E) exhibited a
      biphasic response from P3 onward. Significantly, the ratio of .V(E)(H) to
      .V(E)(N) was generally > 1 during development, except for P13-16, when it was < 1
      after the first 1-2 min, with the lowest value at P13; (3) the H : N ratio for f,
      V(T) and .V(E) during the first 30 s and the last minute of hypoxia all showed a
      distinct dip at P13, after which the V(T) and .V(E) values rose again, while the
      f values declined through P21; and (4) the H : N ratios for f, V(T) and .V(E)
      averaged over 5 min of hypoxia all exhibited a sudden fall at P13. The f ratio
      remained low thereafter, while those for V(T) and .V(E) increased again with age
      until P21. Thus, hypoxic ventilatory response is influenced by both f and V(T)
      before P13, but predominantly by V(T) after P13. The striking changes in normoxic
      ventilation as well as HVR at or around P13, together with our previous
      neurochemical and metabolic data, strongly suggests that the end of the second
      postnatal week is a critical period of development for brainstem respiratory
      nuclei in the rat.

PMID- 17038424
TI  - The oestrogen receptor beta contributes to sex related differences in endothelial
      function of murine small arteries via EDHF.
AB  - Sex related differences in cardiovascular function have been reported in
      oestrogen receptor beta knockout (ERbetaKO) mice. In this study we examined the
      role of endothelium-derived hyperpolarizing factor (EDHF) in differences in small
      artery endothelial function between ERbetaKO and wild-type (WT) mice. Small
      femoral arteries were isolated from ERbetaKO and WT mice and mounted on a wire
      myograph. Concentration-response curves to ACh were compared before and after
      incubation with inhibitors of nitric oxide (NO) and prostacyclin (PGI2)
      synthesis. Comparison of the expression of the principal vascular connexins
      (Cx37, 40 and 43), implicated in EDHF-mediated dilatation were undertaken by
      immunohistochemistry. Vascular ultrastructure was studied by transmission and
      scanning electron microscopy. ACh-induced relaxation of arteries (< 200 microm
      internal diameter) was greater in WT females versus males and was attributable to
      a greater EDHF component of relaxation. This sex difference was absent in
      ERbetaKO mice. Arteries from ERbetaKO males (but not females) were more sensitive
      to ACh compared to WT. The pharmacological evidence and morphological
      prerequisite for involvement of gap junctions in EDHF-mediated responses was
      confirmed in male arteries. The absence of ERbeta had no influence on expression
      of main Cx subtypes within vascular wall or on ultrastructure and morphology of
      the endothelium. The data suggest that in WT male mice, ERbeta reduces EDHF
      mediated relaxation through gap junction communication.

PMID- 17038425
TI  - Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal
      muscle.
AB  - 5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism
      and is regulated in muscle during exercise. We have previously established that
      only three of 12 possible AMPK alpha/beta/gamma-heterotrimers are present in
      human skeletal muscle. Previous studies describe discrepancies between total AMPK
      activity and regulation of its target acetyl-CoA-carboxylase (ACC)beta. Also,
      exercise training decreases expression of the regulatory gamma3 AMPK subunit and
      attenuates alpha2 AMPK activity during exercise. We hypothesize that these
      observations reflect a differential regulation of the AMPK heterotrimers. We
      provide evidence here that only the alpha2/beta2/gamma3 subunit is phosphorylated
      and activated during high-intensity exercise in vivo. The activity associated
      with the remaining two AMPK heterotrimers, alpha1/beta2/gamma1 and
      alpha2/beta2/gamma1, is either unchanged (20 min, 80% maximal oxygen uptake ) or
      decreased (30 or 120 s sprint-exercise). The differential activity of the
      heterotrimers leads to a total alpha-AMPK activity, that is decreased (30 s
      trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity
      associated with the alpha2/beta2/gamma3 heterotrimer was strongly correlated to
      gamma3-associated alpha-Thr-172 AMPK phosphorylation (r(2) = 0.84, P < 0.001) and
      to ACCbeta Ser-221 phosphorylation (r(2) = 0.65, P < 0.001). These data single
      out the alpha2/beta2/gamma3 heterotrimer as an important actor in exercise
      regulated AMPK signalling in human skeletal muscle, probably mediating
      phosphorylation of ACCbeta.

PMID- 17038426
TI  - Histaminergic and glycinergic modulation of GABA release in the vestibular nuclei
      of normal and labyrinthectomised rats.
AB  - Vestibular compensation (the behavioural recovery that follows unilateral
      vestibular de-afferentation), is facilitated by histamine, and is associated with
      increased central histamine release and alterations in histamine H(3) receptor
      expression in the vestibular nuclei. However, little is known of the effects of
      histamine on neurotransmission in the vestibular nuclei, and the mechanisms by
      which histamine may influence compensation are unclear. Here we examined the
      modulatory effects of histaminergic agents on the release of amino acid
      neurotransmitters in slices of the medial vestibular nucleus (MVN) prepared from
      normal and labyrinthectomised rats. The release of GABA, but not glutamate,
      glycine or aspartate, was robustly and reproducibly evoked by a high-K(+)
      stimulus applied to normal MVN slices. Histamine inhibited the evoked release of
      GABA, both through a direct action on presynaptic H(3) receptors (presumably
      located on GABAergic terminals), and through a novel, indirect pathway that
      involved the increased release of glycine by activation of postsynaptic H(1)/H(2)
      receptors (presumably on glycinergic neurons). After unilateral labyrinthectomy
      (UL), the direct H(3) receptor-mediated inhibition of GABA release was profoundly
      downregulated in both ipsi-lesional and contra-lesional MVNs. This effect
      appeared within 25 h post-UL and persisted for at least 3 weeks post-UL. In
      addition, at 25 h post-UL the indirect glycinergic pathway caused a marked
      suppression of GABA release in the contra-lesional but not ipsi-lesional MVN,
      which was overcome by strychnine. Stimulation of histamine H(3) receptors at 25 h
      post-UL restored contra-lesional GABA release to normal, suggesting that acutely
      after UL H(3) receptors may strongly modulate glycinergic and GABAergic
      neurotransmission in the MVN. These findings are the first to demonstrate the
      modulatory actions of the histaminergic system on neurotransmission in the
      vestibular nuclei, and the changes that occur during vestibular system
      plasticity. During vestibular compensation, histaminergic modulation of glycine
      and GABA release may contribute to the rebalancing of neural activity in the
      vestibular nuclei of the lesioned and intact sides.

PMID- 17038427
TI  - Genetically encoded Ca2+ indicators: using genetics and molecular design to
      understand complex physiology.
AB  - This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on
      the use of these novel molecules in the context of understanding complex cell
      signalling in mammals, in vivo. The review focuses on the advantages and
      limitations of specific GECI design strategies and the results of experiments in
      which these molecules have been expressed in transgenic mice, concentrating
      particularly on recent experiments from our laboratory in which physiological
      signalling could be monitored in vivo. Finally, newer strategies for effective
      genetic specification of GECIs are briefly reviewed.

PMID- 17038428
TI  - Reduced nicotinic receptor function in sympathetic ganglia is responsible for the
      hypothermia in the acetylcholinesterase knockout mouse.
AB  - Cholinergic signalling in the sympathetic ganglia (SG) contributes to non
      shivering thermogenesis by relaying the activation signal from the brain to SG
      neurons which activate many peripheral tissues to produce heat. Paradoxically,
      acetylcholinesterase (AChE) inhibitors, which should enhance cholinergic
      signalling, induce hypothermia. To understand the mechanism of how cholinergic
      signalling in the SG controls thermoregulation, we analysed infant AChE knockout
      mice, which are known to show hypothermia by postnatal day 15. Nicotinic receptor
      currents were reduced in acutely dissociated SG neurons of the AChE-deficient
      mice by over 40% compared with wild-type mice. When wild-type neurons were
      treated for 1 h with either oxotremorine-M, a muscarinic agonist, or nicotine,
      the amplitude of nicotinic receptor currents was also decreased by 40%. The
      hypothermia in AChE mutant mice was fully rescued by a peripheral injection of
      both ivermectin, which increases nicotinic receptor currents, and methyl
      atropine, a muscarinic antagonist. Our results demonstrate that the hypothermia
      induced by the lack of AChE activity is primarily caused by a downregulation of
      nicotinic receptors via prolonged stimulation of muscarinic and nicotinic
      receptors in SG neurons. The stationary noise analysis of the nicotinic receptor
      current traces showed that the properties of single-channel activities were not
      different between the two genotypes, suggesting that the primary reason for
      downregulation of nicotinic receptors is due to a reduction of the receptors on
      the surface.

PMID- 17038429
TI  - Response characteristics of the pigeon's pretectal neurons to illusory contours
      and motion.
AB  - Misinterpretations of visual information received by the retina are called visual
      illusions, which are known to occur in higher brain areas. However, whether they
      would be also processed in lower brain structures remains unknown, and how to
      explain the neuronal mechanisms underlying the motion after-effect is intensely
      debated. We show by extracellular recording that all motion-sensitive neurons in
      the pigeon's pretectum respond similarly to real and illusory contours, and their
      preferred directions are identical for both contours in unidirectional cells,
      whereas these directions are changed by 90 deg for real versus illusory contours
      in bidirectional cells. On the other hand, some pretectal neurons produce
      inhibitory (excitatory) after-responses to cessation of prolonged motion in the
      preferred (null) directions, whose time course is similar to that of the motion
      after-effect reported by humans. Because excitatory and inhibitory receptive
      fields of a pretectal cell overlap in visual space and possess opposite
      directionalities, after-responses to cessation of prolonged motion in one
      direction may create illusory motion in the opposite direction. It appears that
      illusory contours and motion could be detected at the earliest stage of central
      information processing and processed in bottom-up streams, and that the motion
      after-effect may result from functional interactions of excitatory and inhibitory
      receptive fields with opposite directionalities.

PMID- 17038430
TI  - Protection conferred by myocardial ATP-sensitive K+ channels in pressure overload
      induced congestive heart failure revealed in KCNJ11 Kir6.2-null mutant.
AB  - Ventricular load can precipitate development of the heart failure syndrome, yet
      the molecular components that control the cardiac adaptive response to imposed
      demand remain partly understood. Compromised ATP-sensitive K(+) (K(ATP)) channel
      function renders the heart vulnerable to stress, implicating this metabolic
      sensor in the homeostatic response that would normally prevent progression of
      cardiac disease. Here, pressure overload was imposed on the left ventricle by
      transverse aortic constriction in the wild-type and in mice lacking sarcolemmal
      K(ATP) channels through Kir6.2 pore knockout (Kir6.2-KO). Despite equivalent
      haemodynamic loads, within 30 min of aortic constriction, Kir6.2-KO showed an
      aberrant prolongation of action potentials with intracellular calcium overload
      and ATP depletion, whereas wild-type maintained ionic and energetic handling. On
      catheterization, constricted Kir6.2-KO displayed compromised myocardial
      performance with elevated left ventricular end-diastolic pressure, not seen in
      the wild-type. Glyburide, a K(ATP) channel inhibitor, reproduced the knockout
      phenotype in the wild-type, whereas the calcium channel antagonist, verapamil,
      prevented abnormal outcome in Kir6.2-KO. Within 48 h following aortic
      constriction, fulminant biventricular congestive heart failure, characterized by
      exercise intolerance, cardiac contractile dysfunction, hepatopulmonary congestion
      and ascites, halved the Kir6.2-KO cohort, while no signs of organ failure or
      mortality were seen in wild-type. Surviving Kir6.2-KO developed premature and
      exaggerated fibrotic myocardial hypertrophy associated with nuclear up-regulation
      of calcium-dependent pro-remodelling MEF2 and NF-AT pathways, precipitating
      chamber dilatation within 3 weeks. Thus, K(ATP) channels appear mandatory in
      acute and chronic cardiac adaptation to imposed haemodynamic load, protecting
      against congestive heart failure and death.

PMID- 17038431
TI  - Purinergic 2 receptor blockade prevents the responses of group IV afferents to
      post-contraction circulatory occlusion.
AB  - ATP, by activating purinergic 2 (P2) receptors on group III and IV afferents, is
      thought to evoke the metabolic component of the exercise pressor reflex.
      Previously we have shown that injection of PPADS, a P2 receptor antagonist, into
      the arterial supply of skeletal muscle of decerebrated cats attenuated the
      responses of group III and IV afferents to static contraction while the muscles
      were freely perfused. We have now tested the hypothesis that injection of PPADS
      (10 mg kg(-1)) attenuated the responses of group III (n = 13) and group IV
      afferents (n = 9) to post-contraction circulatory occlusion. In the present
      study, we found that PPADS attenuated the group III afferent responses to static
      contraction during circulatory occlusion (P < 0.05). Likewise, PPADS abolished
      the group IV afferent responses to static contraction during occlusion (P =
      0.001). During a 1 minute period of post-contraction circulatory occlusion, four
      of the 13 group III afferents and eight of the nine group IV afferents maintained
      their increased discharge. A Fischer's exact probability test revealed that more
      group IV afferents than group III afferents were stimulated by post-contraction
      circulatory occlusion (P < 0.02). In addition, the nine group IV afferents
      increased their mean discharge rate over baseline levels during the post
      contraction circulatory occlusion period, whereas the 13 group III afferents did
      not (P < 0.05). PPADS abolished this post-contraction increase in discharge by
      the group IV afferents (P < 0.05). Our findings suggest that P2 receptors on
      group IV afferents play a role in evoking the metabolic component of the exercise
      pressor reflex.

PMID- 17038432
TI  - Mouse models of long QT syndrome.
AB  - Congenital long QT syndrome is a rare inherited condition characterized by
      prolongation of action potential duration (APD) in cardiac myocytes, prolongation
      of the QT interval on the surface electrocardiogram (ECG), and an increased risk
      of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of
      cardiac ion channel genes that affect repolarization cause the majority of the
      congenital cases. Despite detailed characterizations of the mutated ion channels
      at the molecular level, a complete understanding of the mechanisms by which
      individual mutations may lead to arrhythmias and sudden death requires study of
      the intact heart and its modulation by the autonomic nervous system. Here, we
      will review studies of molecularly engineered mice with mutations in the genes
      (a) known to cause long QT syndrome in humans and (b) specific to cardiac
      repolarization in the mouse. Our goal is to provide the reader with a
      comprehensive overview of mouse models with long QT syndrome and to emphasize the
      advantages and limitations of these models.

PMID- 17038433
TI  - Macrophages promote muscle membrane repair and muscle fibre growth and
      regeneration during modified muscle loading in mice in vivo.
AB  - Muscle injury or modified muscle use can stimulate muscle invasion by leucocytes
      that have the potential to increase tissue damage or promote tissue growth and
      repair. In the present investigation, we examined the role of macrophages in
      muscle injury, repair and regeneration during modified muscle loading. Weight
      bearing was removed from the hindlimbs of mice for 10 days followed by reloading
      through normal ambulation. During the unloading period, soleus muscle fibre cross
      section decreased by 38%. Prior to the onset of reloading, mice received a series
      of intraperitoneal injections of anti-F4/80, which binds a mouse macrophage
      surface antigen. Although anti-F4/80 injections did not affect macrophage numbers
      in soleus muscles at 2 days of reloading, macrophages were reduced by 86% at 4
      days of reloading. Muscle membrane lysis during the reloading period did not
      differ at 2 days of reloading between anti-F4/80-treated mice and mice that
      received isotype control antibody. However, control animals showed large
      decreases in the number of fibres with membrane lesions at 4 days of reloading,
      but this membrane repair did not occur in macrophage-depleted mice. Macrophage
      depletion also reduced muscle regeneration (indicated by central nucleation) and
      satellite cell differentiation (indicated by reductions in MyoD-expressing
      satellite cells) and prevented growth of muscle fibres that normally occurred in
      control animals between days 2 and 4 of reloading. These findings collectively
      show that macrophages play a significant role in muscle fibre membrane repair,
      regeneration and growth during increased muscle use after a period of atrophy.

PMID- 17038434
TI  - Mechanosensitive currents in the neurites of cultured mouse sensory neurones.
AB  - Almost all sensory neurones in the dorsal root ganglia have a mechanosensory
      function. The transduction of mechanical stimuli in vivo takes place exclusively
      at the sensory ending. For cutaneous sensory receptors it has so far proved
      impossible to directly record the mechanically gated receptor potential because
      of the small size and inaccessibility of the sensory ending. Here we investigate
      whether mechanosensitive currents are present in the neurites of freshly isolated
      adult mouse sensory neurones in culture. Almost all sensory neurone neurites
      possess currents gated by submicrometre displacement stimuli (92%). Three types
      of mechanically activated conductance were characterized based on different
      inactivation kinetics. A rapidly adapting conductance was found in larger sensory
      neurones with narrow action potentials characteristic of mechanoreceptors. Slowly
      and intermediate adapting conductances were found exclusively in putative
      nociceptive neurones. Mechanically activated currents with similar kinetics were
      found also after stimulating the cell soma. However, soma currents were only
      observed in around 60% of cells tested and the displacement threshold was several
      times larger than for the neurite (approximately 6 microm). The reversal
      potential of the rapidly adapting current indicated that this current is largely
      selective for sodium ions whereas the slowly adapting current is non-selective.
      It is likely that distinct ion channel entities underlie these two currents. In
      summary, our data suggest that the high sensitivity and robustness of
      mechanically gated currents in the sensory neurite make this a useful in vitro
      model for the mechanosensitive sensory endings in vivo.

PMID- 17038435
TI  - Myoglobin translational diffusion in rat myocardium and its implication on
      intracellular oxygen transport.
AB  - Current theory of respiratory control invokes a role of myoglobin (Mb)
      facilitated O2 diffusion in regulating the intracellular O2 flux, provided Mb
      diffusion can compete effectively with free O2 diffusion. Pulsed-field gradient
      NMR methods have now followed gradient-dependent changes in the distinct 1H NMR
      gamma CH3 Val E11 signal of MbO2 in perfused rat myocardium to obtain the
      endogenous Mb translational diffusion coefficient (D(Mb)) of 4.24 x 10(-7) cm2 s(
      1) at 22 degrees C. The D(Mb) matches precisely the value predicted by in vivo
      NMR rotational diffusion measurements of Mb and shows no orientation preference.
      Given values in the literature for the Krogh's free O2 diffusion coefficient
      (K0), myocardial Mb concentration and a partial pressure of O2 that half
      saturates Mb (P50), the analysis yields an equipoise diffusion P(O2) of 1.77
      mmHg, where Mb and free O2 contribute equally to the O2 flux. In the myocardium,
      Mb-facilitated O2 diffusion contributes increasingly more than free O2 diffusion
      when the P(O2) falls below 1.77 mmHg. In skeletal muscle, the P(O2) must fall
      below 5.72 mmHg. Altering the Mb P50 induces modest change. Mb-facilitated
      diffusion has a higher poise in skeletal muscle than in myocardium. Because the
      basal P(O2) hovers around 10 mmHg, Mb does not have a predominant role in
      facilitating O2 transport in myocardium but contributes significantly only when
      cellular oxygen falls below the equipoise diffusion P(O2).

PMID- 17038437
TI  - Power spectral analysis in mice: What are the appropriate frequency bands?

PMID- 17038436
TI  - The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires
      interactions among transmembrane segments of the transporter.
AB  - The electrogenic Na+-HCO3- cotransporter (NBCe1) plays a central role in
      intracellular pH (pHi) regulation as well as HCO3- secretion by pancreatic ducts
      and HCO3- reabsorption by renal proximal tubules. To understand the structural
      requirements for the electrogenicity of NBCe1, we constructed chimeras of NBCe1-A
      and the electroneutral NBCn1-B, and used two-electrode voltage clamp to measure
      electrogenic transporter current in Xenopus oocytes exposed to 5% CO2-26 mm HCO3-
      (pH 7.40). The chimera consisting of NBCe1-A (i.e. NBCe1-A 'background') with the
      cytoplasmic N-terminal domain (Nt) of NBCn1-B had a reversal potential of -156.3
      mV (compared with a membrane potential Vm of -43.1 mV in a HCO3(-)-free solution)
      and a slope conductance of 3.0 microS (compared with 12.5 microS for NBCe1-A).
      Also electrogenic were chimeras with an NBCe1-A background but with NBCn1-B
      contributing the extracellular loop (L) between transmembrane segment (TM) 5 and
      6 (-140.9 mV/11.1 microS), the cytoplasmic C-terminal domain (Ct; -123.8 mV/9.7
      microS) or Nt + L + Ct (-120.9 mV/3.7 microS). Reciprocal chimeras (with an NBCn1
      background but with NBCe1 contributing Nt, L, Ct or Nt + L + Ct) produced no
      measurable electrogenic transporter currents in the presence of CO2-HCO3-. pHi
      recovered from an acid load, but without the negative shift of Vm that is
      characteristic of electrogenic Na+-HCO3- cotransporters. Thus, these chimeras
      were electroneutral, as were two others consisting of NBCe1(Nt-L)/NBCn1(TM6-Ct)
      and NBCn1(Nt-L)/NBCe1(TM6-Ct). We propose that the electrogenicity of NBCe1
      requires interactions between TM1-5 and TM6-13.

PMID- 17038439
TI  - Hemodynamic analysis of Hyrtl anastomosis in human placenta.
AB  - The Hyrtl anastomosis is a common connection between the umbilical arteries near
      the cord insertion in most human placentas. It has been speculated that it
      equalizes the blood pressure between the territories supplied by the umbilical
      arteries. However, its functional role in the regulation and distribution of
      fetal blood flow to the placenta has not yet been explored. A computational model
      has been developed for quantitative analysis of hemodynamic characteristic of the
      Hyrtl anastomosis in cases of discordant blood flow in the umbilical arteries.
      Simulations were performed for cases of either increased placental resistance at
      the downstream end or reduced arterial blood flow due to some pathologies
      upstream of one of the arteries. The results indicate that when placental
      territories of one artery impose increased resistance to fetal blood flow, the
      Hyrtl anastomosis redistributes the blood flow into the second artery to reduce
      the large pressure gradients that are developed in the affected artery. When one
      of the arteries conducts a smaller blood flow into the placenta and a relatively
      smaller pressure gradient is developed, the Hyrtl anastomosis rebuilds the
      pressure gradients in the affected artery and redistributes blood flow from the
      unaffected artery to the affected one to improve placental perfusion. In
      conclusion, the Hyrtl anastomosis plays the role of either a safety valve or a
      pressure stabilizer between the umbilical arteries at the placental insertion.

PMID- 17038438
TI  - Optimal frequency ranges for extracting information on cardiovascular autonomic
      control from the blood pressure and pulse interval spectrograms in mice.
AB  - The analysis of blood pressure (BP) and heart rate (HR) variability by spectral
      methods has proven a useful tool in many animal species for the assessment of the
      vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP
      measurements obtained in mice by telemetry were used to characterize the spectral
      bandwidths of autonomic relevance by using an approach with no a priori. The
      paradigm was based on the autonomic blockades obtained with conventional drugs
      (atropine, prazosin, atenolol). The spectral changes were estimated in all of the
      combinations of spectral bandwidths. The effect of hydralazine was also tested
      using the same systematic analysis, to detect the zones of sympathetic activation
      resulting reflexly from the vasodilatory action of the drug. Two zones of
      interest in the study of the autonomic control of BP and HR were observed. The
      first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and
      corresponds to the low-frequency zone (or Mayer waves). This zone reflects
      sympathetic control since the power spectral density of this zone was
      significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was
      significantly amplified as a result of a reflex sympathetic activation
      (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval
      spectrum and corresponded to the high-frequency zone (respiratory sinus
      arrhythmia) under vagal control (blocked by atropine). These zones are
      recommended for testing the autonomic control of circulation in mice.

PMID- 17038440
TI  - Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon
      like peptide-1 receptor.
AB  - Oxyntomodulin (OXM), a postprandially released intestinal hormone, inhibits food
      intake via the glucagon-like peptide-1 receptor (GLP-1R). Although OXM may have
      clinical value in treating obesity, the cardiovascular effects of OXM are not
      well understood. Using telemetry to measure heart rate (HR), body temperature
      (Tb), and activity in conscious and freely moving mice, we tested 1) whether OXM
      affects HR and 2) whether this effect is mediated by the GLP-1R. We found that
      peripherally administered OXM significantly increased HR in wild-type mice,
      raising HR by >200 beats/min to a maximum of 728 +/- 11 beats/min. To determine
      the extent to which the sympathetic nervous system mediates the tachycardia of
      OXM, we delivered this hormone to mice deficient in dopamine-beta-hydroxylase
      [Dbh(-/-) mice], littermate controls [Dbh(+/-) mice], and autonomically blocked
      C57Bl mice. OXM increased HR equally in all groups (192 +/- 13, 197 +/- 21, and
      216 +/- 11 beats/min, respectively), indicating that OXM elevated intrinsic HR.
      Intrinsic HR was also vigorously elevated by OXM in Glp-1R(-/-) mice (200 +/- 28
      beats/min). In addition, peripherally administered OXM inhibited food intake and
      activity levels in wild-type mice and lowered Tb in autonomically blocked mice.
      None of these effects were observed in Glp-1R(-/-) mice. These data suggest
      multiple modes of action of OXM: 1) it directly elevates murine intrinsic HR
      through a GLP-1R-independent mechanism, perhaps via the glucagon receptor or an
      unidentified OXM receptor, and 2) it lowers food intake, activity, and Tb in a
      GLP-1R-dependent fashion.

PMID- 17038441
TI  - Sex-related effects on venous compliance and capillary filtration in the lower
      limb.
AB  - Recent studies in humans have suggested sex differences in venous compliance of
      the lower limb, with lower compliance in women. Capillary fluid filtration could,
      however, be a confounder in the evaluation of venous compliance. The venous
      capacitance and capillary filtration response in the calves of 12 women (23.2 +/-
      0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body
      negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is
      dependent on pressure and was determined using the first derivative of a
      quadratic regression equation that described the capacitance-pressure
      relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a
      lower venous compliance in women at low transmural pressures, and the venous
      capacitance in men was increased (P < 0.05). However, the difference in
      compliance between sexes was reduced and not seen at higher transmural pressures.
      Net capillary fluid filtration and capillary filtration coefficient (CFC) were
      greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume
      increase (capacitance response + total capillary filtration) during LBNP was
      equivalent in both sexes. When total capillary filtration was not subtracted from
      the calf capacitance response in the calculation of venous compliance, the sex
      differences disappeared, emphasizing that venous compliance measurement should be
      corrected for the contribution of CFC.

PMID- 17038442
TI  - Sex differences in energy metabolism and performance of teleost cardiac tissue.
AB  - This study examined the effects of different oxygenation levels and substrate
      availability on cardiac performance, metabolism, and biochemistry in sexually
      immature male and female rainbow trout (Oncorhynchus mykiss). Ventricle strips
      were electrically paced (0.5 Hz, 14 degrees C) in hyperoxic or hypoxic Ringer
      solution. Our results demonstrate that 1) males sustain isometric force
      production (F) longer than females under hyperoxia (P O2 = 640 mmHg) with
      exogenous glucose present; 2) contractility is not maintained under moderate (P
      O2 = 130 mmHg) or severe hypoxia (P O2 = 10-20 mmHg) with glucose in either sex;
      however, following reoxygenation, F is higher in females compared with males; and
      3) female tissue has higher lactate levels, net lactate efflux, and lactate
      dehydrogenase activity than males, whereas males have higher glycogen, citrate
      synthase, and beta-hydroxy acyl-CoA dehydrogenase activities, and greater
      inotropic responses to exogenous glucose and octanoate. No sex differences were
      detected in responsiveness to epinephrine and inhibitors of glucose transport or
      activities of hexokinase and pyruvate kinase. We conclude that sex differences
      exist in rainbow trout cardiac tissue: females appear to prefer glycolysis for
      ATP production, whereas males have a higher capacity for aerobic and lipid
      metabolism.

PMID- 17038443
TI  - Myofilament response to Ca2+ and Na+/H+ exchanger activity in sex hormone-related
      protection of cardiac myocytes from deactivation in hypercapnic acidosis.
AB  - Compared to sham-operated controls, myofilaments from hearts of ovariectomized
      (OVX) rats demonstrate an increase in Ca2+ sensitivity with no change in maximum
      tension (Wattanapermpool J and Reiser PJ. Am J Physiol 277: H467-H473, 1999). To
      test the significance of this modification in intact cells, we compared
      intracellular Ca2+ transients and shortening of ventricular myocytes isolated
      from sham and 10-wk OVX rats. There was a decrease in the peak Ca2+ transient
      with prolonged 50% decay time in OVX cardiac myocytes without changes in the
      resting intracellular Ca2+ concentration. Percent cell shortening was also
      depressed, and relaxation was prolonged in cardiac myocytes from OVX rats
      compared with shams. Ovariectomy induced a sensitization of the myofilaments to
      Ca2+. Hypercapnic acidosis suppressed the shortening of OVX myocytes to a lesser
      extent than that detected in shams. Moreover, a larger compensatory increase in
      %cell shortening was obtained in OVX myocytes during prolonged acidosis. The
      elevated compensation in cell shortening was related to a higher amount of
      increase in the amplitude of the Ca2+ transient in OVX myocytes. However, these
      differences in Ca2+ transients and %cell shortening were no longer evident in the
      presence of 1 microM cariporide, a specific inhibitor of Na+/H+ exchanger type 1
      (NHE1). Our results indicate that deprivation of female sex hormones modulates
      the intracellular Ca2+ concentration in cardiac myocytes, possibly via an
      increased NHE1 activity, which may act in concert with Ca2+ hypersensitivity of
      myofilament activation as a determinant of sex differences in cardiac function.

PMID- 17038444
TI  - Hypersensitivity of myofilament response to Ca2+ in association with
      maladaptation of estrogen-deficient heart under diabetes complication.
AB  - The amelioration of cardioprotective effect of estrogen in diabetes suggests
      potential interactive action of estrogen and insulin on myofilament activation.
      We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar
      preparations from hearts of sham and 10-wk ovariectomized rats with or without
      simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats
      with estrogen and/or insulin supplementation. Similar magnitude of suppressed
      maximum myofibrillar ATPase activity was demonstrated in ovariectomized,
      diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and
      the relative suppression in alpha-myosin heavy chain level in ovariectomy
      combined with diabetes could be completely restored by estrogen and insulin
      supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only
      in the ovariectomized but not diabetic group was also observed in diabetic
      ovariectomized rats, which was restored upon estrogen supplementation. Binding
      kinetics of beta1-adrenergic receptors and immunoblots of beta1-adrenoceptors as
      well as heat shock 72 (HSP72) were analyzed to determine the association of
      changes in receptors and HSP72 to that of the myofilament response to Ca2+. The
      amount of beta1-adrenoceptors significantly increased concomitant with Ca2+
      hypersensitivity of the myofilament, without differences in the receptor binding
      affinity among the groups. In contrast, changes in HSP72 paralleled that of
      maximum myofibrillar ATPase activity. These results indicate that
      hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in
      ovariectomized rats even under diabetes complication and that alterations in the
      expression of beta1-adrenoceptors may, in part, play a mechanistic role
      underlying the cardioprotective effects of estrogen that act together with Ca2+
      hypersensitivity of the myofilament in determining the gender difference in
      cardiac activation.

PMID- 17038445
TI  - Role of glucocorticoid receptor in acclimation of killifish (Fundulus
      heteroclitus) to seawater and effects of arsenic.
AB  - Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of
      the seawater. It is generally accepted that acclimation to seawater is mediated
      by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR
      mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no
      direct evidence in killifish that the GR stimulates CFTR gene expression,
      quantitative PCR studies were conducted to test the hypothesis that cortisol
      activation of GR upregulates CFTR mRNA expression and that this response is
      required for acclimation to seawater. Inhibition of the GR by RU-486 prevented
      killifish from acclimating to increased salinity and blocked the increase in CFTR
      mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone
      had no effect on acclimation to seawater. Thus acclimation to increased salinity
      in killifish requires signaling via the GR and includes an increase in CFTR gene
      expression. Because arsenic, a toxic metalloid that naturally occurs in the
      aquatic environment, has been shown to disrupt GR transcriptional regulation in
      avian and mammalian systems, studies were also conducted to determine whether
      arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in
      vivo fish model and thereby blocks the ability of killifish to acclimate to
      increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR
      protein abundance. However, arsenic did not disrupt the GR-induced increase in
      CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a
      mechanism that does not disrupt GR-mediated induction of CFTR gene expression.

PMID- 17038446
TI  - Nitric oxide impairs baroreflex gain during acute psychological stress.
AB  - Psychological stress can suppress baroreflex function, but the mechanism has not
      been fully elucidated. Nitric oxide in the brain and in the adrenal cortex, as
      well as plasma glucocorticoids, increases during stress and has been shown to
      suppress reflex gain in unstressed animals. Therefore, the purpose of this study
      was to test the hypothesis that stress, caused by exposure to a novel
      environment, decreases baroreflex gain in rabbits through the actions of nitric
      oxide to increase corticosterone release. Baroreflex control of heart rate and
      plasma corticosterone levels was quantified before and after blockade of nitric
      oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 20 mg/kg iv) in
      conscious rabbits exposed to a novel environment and in the same rabbits once
      they had been conditioned to the environment. Stress significantly reduced
      baroreflex gain from -23.4 +/- 2 to -12.2 +/- 1.6 beats x min(-1) x mmHg(-1) (P <
      0.05) and increased plasma corticosterone levels from 5.4 +/- 0.7 to 15.5 +/- 5.0
      ng/ml (P < 0.05). NOS blockade increased gain in stressed animals (to -27.2 +/-
      5.4 beats x min(-1) x mmHg(-1), P < 0.05) but did not alter gain in unstressed
      rabbits (-26.8 +/- 4.9 beats x min(-1) x mmHg(-1)) such that gain was equalized
      between the two states. NOS blockade increased plasma corticosterone levels in
      unstressed animals (to 14.3 +/- 2.1 ng/ml, P < 0.05) but failed to significantly
      alter levels in stressed rabbits (14.0 +/- 3.9 ng/ml). In conclusion,
      psychological stress may act via nitric oxide, independently of increases in
      corticosterone, to decrease baroreflex gain.

PMID- 17038447
TI  - Gill Na+-K+-ATPase activity correlates with basolateral membrane lipid
      composition in seawater- but not freshwater-acclimated Arctic char (Salvelinus
      alpinus).
AB  - The successful migration of euryhaline teleost fish from freshwater to seawater
      requires the upregulation of gill Na+-K+-ATPase, an ion transport enzyme located
      in the basolateral membrane (BLM) of gill chloride cells. Following 39 days of
      seawater exposure, Arctic char had similar plasma sodium and chloride levels as
      individuals maintained in freshwater, indicating they had successfully acclimated
      to seawater. This acclimation was associated with an eightfold increase in gill
      Na+-K+-ATPase activity but only a threefold increase in gill Na+-K+-ATPase
      protein number, suggesting that other mechanisms may also modulate gill Na+-K+
      ATPase activity. We therefore investigated the influence of membrane composition
      on Na+-K+-ATPase activity by examining the phospholipid, fatty acid, and
      cholesterol composition of the gill BLM from freshwater- and seawater-acclimated
      Arctic char. Mean gill BLM cholesterol content was significantly lower (
      approximately 22%) in seawater-acclimated char. Gill Na+-K+-ATPase activity in
      individual seawater Arctic char was negatively correlated with BLM cholesterol
      content and positively correlated with %phosphatidylethanolamine and overall
      %18:2n6 (linoleic acid) content of the BLM, suggesting gill Na+-K+-ATPase
      activity of seawater-acclimated char may be modulated by the lipid composition of
      the BLM and may be especially sensitive to those parameters known to influence
      membrane fluidity. Na+-K+-ATPase activity of individual freshwater Arctic char
      was not correlated to any membrane lipid parameter measured, suggesting that
      different lipid-protein interactions may exist for char living in each
      environment.

PMID- 17038448
TI  - Evolutionary model selection with a genetic algorithm: a case study using stem
      RNA.
AB  - The choice of a probabilistic model to describe sequence evolution can and should
      be justified. Underfitting the data through the use of overly simplistic models
      may miss out on interesting phenomena and lead to incorrect inferences.
      Overfitting the data with models that are too complex may ascribe biological
      meaning to statistical artifacts and result in falsely significant findings. We
      describe a likelihood-based approach for evolutionary model selection. The
      procedure employs a genetic algorithm (GA) to quickly explore a combinatorially
      large set of all possible time-reversible Markov models with a fixed number of
      substitution rates. When applied to stem RNA data subject to well-understood
      evolutionary forces, the models found by the GA 1) capture the expected overall
      rate patterns a priori; 2) fit the data better than the best available models
      based on a priori assumptions, suggesting subtle substitution patterns not
      previously recognized; 3) cannot be rejected in favor of the general reversible
      model, implying that the evolution of stem RNA sequences can be explained well
      with only a few substitution rate parameters; and 4) perform well on simulated
      data, both in terms of goodness of fit and the ability to estimate evolutionary
      rates. We also investigate the utility of several distance measures for comparing
      and contrasting inferred evolutionary models. Using widely available small
      computer clusters, our approach allows, for the first time, to evaluate the
      performance of existing RNA evolutionary models by comparing them with a large
      pool of candidate models and to validate common modeling assumptions. In
      addition, the new method provides the foundation for rigorous selection and
      comparison of substitution models for other types of sequence data.

PMID- 17038449
TI  - Predicting gene expression level from codon usage bias.
AB  - The "expression measure" of a gene, E(g), is a statistic devised to predict the
      level of gene expression from codon usage bias. E(g) has been used extensively to
      analyze prokaryotic genome sequences. We discuss 2 problems with this approach.
      First, the formulation of E(g) is such that genes with the strongest selected
      codon usage bias are not likely to have the highest predicted expression levels;
      indeed the correlation between E(g) and expression level is weak among moderate
      to highly expressed genes. Second, in some species, highly expressed genes do not
      have unusual codon usage, and so codon usage cannot be used to predict expression
      levels. We outline a simple approach, first to check whether a genome shows
      evidence of selected codon usage bias and then to assess the strength of bias in
      genes as a guide to their likely expression level; we illustrate this with an
      analysis of Shewanella oneidensis.

PMID- 17038450
TI  - Controlling the obesity epidemic is important for maintaining musculoskeletal
      health.

PMID- 17038451
TI  - Obesity and osteoarthritis: more complex than predicted!

PMID- 17038452
TI  - Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a
      population-based study.
AB  - BACKGROUND: Although age is the strongest predictor of osteoarthritis, the exact
      mechanism underlying this disorder remains elusive. OBJECTIVE: To examine the
      association between leucocyte telomere length (LTL), a bio-indicator of ageing,
      and radiographic hand osteoarthritis. METHODS: An unselected, predominantly
      female sample from the TwinsUK Adult Twin Registry (Twin Research and Genetic
      Epidemiology Unit, St Thomas Hospital, London, UK) was studied. Radiographs of
      both hands were obtained with a standard posteroanterior view and assessed for
      radiographic osteoarthritis according to the Kellgren/Lawrence (K/L) score.
      Individual radiographic features including osteophytes and joint space narrowing
      (JSN) were also assessed on a four-point scale using a standard atlas. Hand
      osteoarthritis was defined radiographically as having >or=3 osteoarthritis
      affected joints of both hands (K/L score>or=2). Severity of hand osteoarthritis
      was indicated semiquantitatively by total K/L scores, osteophytes, JSN scores and
      proportion of joints affected. Mean LTL was measured by the terminal restriction
      fragment length using the Southern blot. RESULTS: A total of 1086 Caucasian
      subjects (mean (SD) age 55 (8.0) years) were studied. LTL was 6.95 (0.64) kb and
      was inversely correlated with age. After adjustment for age, sex, body mass index
      and smoking, LTL was significantly shorter by 178 bp in subjects with hand
      osteoarthritis (n = 160) than in those without (n = 926; p = 0.04). LTL was also
      significantly associated with semicontinuous measures of osteoarthritis (eg,
      total K/L score, JSN score, osteophyte score and proportion of joints affected)
      after adjustment (all p<or=0.02) in a dose-response fashion. CONCLUSION: Shorter
      LTL equivalent to around 11 years of annual loss in normal people is associated
      with radiographic hand osteoarthritis and disease severity, suggesting potential
      shared mechanisms between osteoarthritis and ageing, and implicating oxidative
      stress and low-level chronic inflammation in both conditions.

PMID- 17038453
TI  - Comparing 10-day and 4-month doxycycline courses for treatment of Chlamydia
      trachomatis-reactive arthritis: a prospective, double-blind trial.
AB  - OBJECTIVE: To compare the efficacy of a 10-day and a 4-month doxycylcine course
      for the treatment of Chlamydia trachomatis-reactive arthritis (Ct-ReA). METHODS:
      Patients with active Ct-ReA were enrolled in a prospective, multicentre, double
      blind, controlled clinical trial and randomised to receive doxycycline 100 mg
      twice daily for 10 days followed either by placebo or by continued doxycycline
      100 mg twice daily over 4 months. Various clinical and laboratory parameters
      referring to disease activity were recorded in the beginning and at the end of
      treatment. RESULTS: 32 of 37 patients included (15 men and 17 women; mean
      (standard deviation) disease duration 17 (13) months completed the study; 17 were
      randomised to short-term doxycycline and placebo (placebo group) and 15 to
      prolonged treatment with doxycycline (doxycycline group) over the 4-month study
      period. After this time, only two patients from each group went into remission.
      There were no drop-outs owing to adverse events or treatment failures.
      CONCLUSIONS: The results of this study suggest that prolonged treatment with a 4
      month course of doxycycline is not superior to short-term treatment over 10 days
      in patients with Ct-ReA.

PMID- 17038454
TI  - Development of new-onset psoriasis while on anti-TNFalpha treatment.

PMID- 17038455
TI  - Refractory auto-inflammatory syndrome associated with digenic transmission of low
      penetrance tumour necrosis factor receptor-associated periodic syndrome and
      cryopyrin-associated periodic syndrome mutations.

PMID- 17038456
TI  - Behcet's disease with life-threatening haemoptoe and pulmonary aneurysms:
      complete remission after infliximab treatment.

PMID- 17038457
TI  - Multiple extra-articular manifestations are associated with poor survival in
      patients with rheumatoid arthritis.

PMID- 17038458
TI  - Tumour necrosis factor alpha blockade and the risk of vasculitis.

PMID- 17038459
TI  - Agreement of Mexican rheumatologists with the ASsessment in Ankylosing
      Spondylitis International Working Group and the EUropean League Against
      Rheumatism recommendations for the management of ankylosing spondylitis.

PMID- 17038460
TI  - Acute abdominal pain in systemic lupus erythematosus: factors contributing to
      recurrence of lupus enteritis.

PMID- 17038461
TI  - Lack of association between signaling lymphocytic activation molecule family
      member 1 gene and rheumatoid arthritis in the French and Tunisian populations.

PMID- 17038462
TI  - Palindromic rheumatism: different genetic background implies a distinct disease
      entity.

PMID- 17038463
TI  - Advances in targeted therapies VIII. Proceedings of the Eighth International
      Symposium on Advances in Targeted Therapy. April 5-9, 2006. Sorrento, Italy.

PMID- 17038464
TI  - More relevant, precise, and efficient items for assessment of physical function
      and disability: moving beyond the classic instruments.
AB  - OBJECTIVES: Patient reported outcomes (PROs) have become standard study
      endpoints. However, little attention has been given to using item improvement to
      advance PRO performance which could improve precision, clarity, patient
      relevance, and information content of "physical function/disability" items and
      thus the performance of resulting instruments. METHODS: The present study
      included 1860 physical function/disability items from 165 instruments. Item
      formulations were assessed by frequency of use, modified Delphi consensus,
      respondent judgement of clarity and importance, and item response theory (IRT).
      Data from 1100 rheumatoid arthritis, osteoarthritis, and normal ageing subjects,
      using qualitative item review, focus groups, cognitive interviews, and patient
      survey were used to achieve a unique item pool that was clear, reliable,
      sensitive to change, readily translatable, devoid of floor and ceiling
      limitations, contained unidimensional subdomains, and had maximal information
      content. RESULTS: A "present tense" time frame was used most frequently, better
      understood, more readily translated, and more directly estimated the latent trait
      of disability. Items in the "past tense" had 80-90% false negatives (p<0.001).
      The best items were brief, clear, and contained a single construct. Responses
      with four to five options were preferred by both experts and respondents. The
      term physical function may be preferable to the term disability because of fewer
      floor effects. IRT analyses of "disability" suggest four independent subdomains
      (mobility, dexterity, axial, and compound) with factor loadings of 0.81-0.99.
      CONCLUSIONS: Major improvement in performance of items and instruments is
      possible, and may have the effect of substantially reducing sample size
      requirements for clinical trials.

PMID- 17038466
TI  - Clinical, radiological, and functional assessment in psoriatic arthritis: is it
      different from other inflammatory joint diseases?

PMID- 17038467
TI  - Outcomes in ankylosing spondylitis: what makes the assessment of treatment
      effects in ankylosing spondylitis different?
AB  - There are four major challenges in the assessment of outcomes in patients with
      ankylosing spondylitis (AS) that are particularly relevant to the evaluation of
      new therapies. Firstly, measures of symptoms and impairment in AS are not
      specific for inflammatory processes, they also capture mechanical symptoms and
      fixed limitations. The non-specific nature of these measures may cause them to be
      less responsive and therefore less useful in determining treatment efficacy.
      Secondly, acute phase reactants have limited value as measures of AS activity and
      other surrogate markers have not yet been established. Thirdly, the assessment of
      the disease modifying potential of new therapies is hampered by the slow rate of
      spinal fusion. Fourthly, work disability has not be studied as an endpoint in
      clinical trials in AS, despite the fact that work disability is an important
      outcome in patients with AS. Research into ways to overcome these challenges in
      outcome measurement will help identify useful therapies and define the range of
      outcomes that they influence.

PMID- 17038465
TI  - Updated consensus statement on biological agents for the treatment of rheumatic
      diseases, 2006.

PMID- 17038468
TI  - Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation
      to tumour necrosis factor and IL-1 in experimental arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by
      chronic joint inflammation and destruction. Interleukin (IL)-17 is a T cell
      cytokine expressed in the synovium and synovial fluid of patients with RA. IL-17
      is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and
      IL-1. IL-17 has been shown to have additive or even synergistic effects with TNF
      and IL-1 during the induction of cytokine expression and joint damage in vitro
      and in vivo. TNFalpha and IL-1 are considered powerful targets in the treatment
      of RA because of their leading role in driving the enhanced production of
      cytokines, chemokines, and degradative enzymes. Besides anti-TNF and anti-IL-1
      therapies, whose clinical efficacy is now established, new targets have been
      proposed for RA which is not responding to conventional treatments. This paper
      discusses the role of IL-17 in experimental arthritis and its interrelationship
      with TNF and IL-1, currently the most targeted cytokines in the treatment of RA.
      IL-17 is involved in both initiation and progression of murine experimental
      arthritis. Studies have shown that IL-17 not only synergises with TNF, but also
      enhances inflammation and destruction independent of IL-1 and TNF. On the basis
      of these studies, the authors propose IL-17 as an interesting additional target
      in the treatment of RA.

PMID- 17038469
TI  - The BLyS/BAFF family of ligands and receptors: key targets in the therapy and
      understanding of autoimmunity.
AB  - The B lymphocyte stimulator (BLyS; also termed BAFF) family of ligands and
      receptors plays a central role in B lymphocyte development, selection, and
      homoeostasis. Members of this family can independently influence different B cell
      subsets, because the interactions between the two ligands and three receptors
      vary, and the receptors themselves are differentially expressed among developing,
      naive, and antigen experienced B cell subsets. These properties prompt careful
      assessment of how ablative therapies may influence the behaviour of upstream or
      downstream B lineage populations, as well as how the implementation and
      expectations of therapeutics targeting BLyS family members must be guided by
      knowledge of the B cell subsets contributing to pathogenesis.

PMID- 17038471
TI  - Can studies of tolerance ever lead to therapy?
AB  - Studies in murine models have suggested that regulatory T (Treg) cells can be
      generated by any antigen and such antigen specific Treg cells not only prevent
      but also reverse unwanted immunity. Another key finding of these experimental
      studies is that Treg cells could possibly be used therapeutically to ameliorate
      disease because of their ability to interfere with the execution of effector
      programmes of fully differentiated T effector cells. However, more work is needed
      before these findings can be safely translated into better targeted therapy and
      prevention of unwanted immune responses in clinical settings.

PMID- 17038470
TI  - Role of nitric oxide in the regulation of T cell functions.
AB  - There is a close relation between T helper (Th) 1 cells and nitric oxide in
      disease. Thus it is possible that a reciprocal regulatory mechanism exists
      between them. This paper briefly describes the experimental studies which have
      helped elucidate the mechanism by which nitric oxide selectively enhances Th 1
      cell proliferation and the potential effect of nitric oxide on regulatory T
      (Treg) cells. On the basis of the results the authors propose that nitric oxide
      represents an additional signal for the induction of T cell subset response,
      contributing to the increasingly complex network of immune regulation essential
      for health and disease.

PMID- 17038472
TI  - Pharmacoeconomics: friend or foe?
AB  - The financial constraints faced by most health systems today make it necessary
      for manufacturers of new, expensive drugs to demonstrate value for money. This
      paper describes the different types of economic evaluation; the increasing use of
      these analysis in decision making; their application to new drugs in the field of
      in rheumatoid arthritis; and the pros and cons of pharmacoeconomics studies from
      the perspective of the patients, the physicians, and the general population.

PMID- 17038474
TI  - Serious infections with antirheumatic therapy: are biologicals worse?
AB  - This paper reviews the current evidence for the role of antirheumatic therapy in
      the development of serious infections in patients with rheumatoid arthritis (RA).
      Prednisone is clearly associated with increased infectious risk, but no
      definitive data link methotrexate to infection. Emerging data suggest that
      biological agents also pose increase infectious risk, particularly when used in
      combination with corticosteroids or methotrexate. Further research is needed in
      this important aspect of RA treatment. In the meantime, the author recommends
      that physicians should remain vigilant for serious infections in their patients
      with RA and use appropriate vaccines and screening procedures to mitigate their
      risk.

PMID- 17038473
TI  - Natalizumab and progressive multifocal leucoencephalopathy.
AB  - Current data suggest that as many as 1 in 1000 treated individuals may develop
      progressive multifocal leucoencephalopathy (PML) in concert with the use of
      natalizumab. Natalizumab was withdrawn in early 2005. The present paper provides
      a comprehensive description of PML and reviews the role of natalizumab in the
      pathogenesis of PML. It is likely that use of drugs which cause specific
      perturbations of the immune system will be accompanied by similar rare
      infections. Thus researchers should be on the alert when using such agents in
      clinical trials.

PMID- 17038475
TI  - Treating rheumatic diseases in pregnancy: dos and don'ts.
AB  - This paper presents a critical appraisal of the current evidence and
      recommendations regarding the use of pharmaceuticals and biologicals in
      pregnancy. Clinical experience is often at variance with published
      recommendations as studies have not taken into account the differences in
      physiology in the various stages of gestation and between animal and human
      pregnancies. Physicians should bear in mind that pregnancy causes disruption in
      several organ systems; the effects of an intervention may depend on the stage of
      gestation; and some effects of interventions in pregnancy may not manifest until
      adulthood.

PMID- 17038476
TI  - IL-32, a novel cytokine with a possible role in disease.
AB  - IL-32 is the name given to the NK4 transcript first reported in IL-2 activated T
      lymphocytes and natural killer cells 13 years ago without known function. The
      novel cytokine has six isoforms. In an study to isolate a soluble form of the IL
      32 receptor from human urine, IL-32alpha bound proteinase-3 with high affinity
      and was not affected by enzyme inhibition. IL-32alpha/IL-32gamma were expressed
      as recombinant molecules. The cytokine exhibits properties characteristic of
      proinflammatory cytokines and also induces the degradation of inhibitory kappaB
      and phosphorylation of mitogen activated protein p38. Monoclonal antibodies to IL
      32 identify its presence in a variety of human tissues from diseases states.
      Epithelial cells from healthy subjects express low levels of the cytokine, but in
      disease conditions such as chronic obstructive pulmonary disease, Crohn's disease
      and psoriasis, the expression increases markedly. IL-32 is a major transcript in
      gene array studies in epithelial cells stimulated with IFNgamma in vitro. In
      rheumatoid arthritis, synovial tissues reveals increased content of IL-32, which
      correlates with severity of disease. A highly significant correlation has been
      observed between the number of synovial and macrophagic cells positive for IL-32
      and the level of erythrocytes sedimentation, IL-1beta, tumour necrosis factor
      alpha, and IL-18. Thus, IL-32 exhibits many properties of proinflammatory
      cytokines and associations with disease severity.

PMID- 17038477
TI  - Heat shock proteins induce T cell regulation of chronic inflammation.
AB  - The significance of immune responses to certain heat shock proteins (HSPs) that
      develop in virtually all inflammatory diseases is only now becoming clear. In
      experimental models, HSPs prevent or arrest inflammatory damage, and initial
      clinical trials in chronic inflammatory disease have shown HSP peptides to
      promote production of anti-inflammatory cytokines-indicating immunoregulatory
      potential. HSPs are ubiquitous self-antigens that are highly expressed in
      inflamed tissues. The prokaryotic homologous proteins, present in every bacterial
      species, are dominantly immunogenic. This is striking, especially as these
      proteins have large areas of sequence homologies with the host (mammalian)
      counterparts. In several experimental models of autoimmune diseases, immunisation
      with bacterial HSPs inhibited disease development, as did oral/nasal
      administration. Based on the experimental evidence so far, it is tempting to
      speculate that: firstly, exposure to homologues of these self-antigens, as
      present in, for instance, the bacterial intestinal flora, has a decisive impact
      on the regulation of self-tolerance at the level of T cells; and secondly, such
      proteins or their derivative peptides may have a role in an antigen specific
      immunotherapy approach involving modulation of relevant T cells, without the
      immediate necessity of defining disease specific autoantigens. Recent findings in
      experimental asthma and atherosclerosis have indicated that the field of
      application of such immunotherapy can be broader than just autoimmunity.

PMID- 17038478
TI  - Interleukin-7 induced immunopathology in arthritis.
AB  - Interleukin (IL)-7 is a potent immunoregulatory cytokine that is detected in
      joints of patients with rheumatoid and juvenile idiopathic arthritis and which
      correlates with parameters of disease. Several synovial cell types that play an
      important role in inflammation and immunopathology, such as macrophages,
      dendritic cells, and fibroblasts, produce IL-7. IL-7 induces cytokines produced
      by arthritogenic T cells (for example, interferon gamma (IFNgamma), IL-17), T
      cell differentiating factors (for example, IL-12), chemokines capable of
      attracting inflammatory cells (for example, macrophage induced gene (MIG),
      macrophage inflammatory protein (MIP)-1alpha) as well as molecules involved in
      cell adhesion, migration, and costimulation (for example, lymphocyte function
      associated antigen (LFA)-1, CD40, CD80). In addition, IL-7 can induce bone loss
      by stimulating osteoclastogenesis that is dependent on receptor activator of
      nuclear factor kappaB ligand (RANKL). IL-7 induces tumour necrosis factor alpha
      (TNFalpha) secretion by T cells and by monocytes after T cell dependent
      monocyte/macrophage activation. Importantly, induction of both IL-7 and IL-7
      induced effects seems to be able to operate independent of TNFalpha. Together
      this suggests that IL-7 is an important cytokine in several rheumatic conditions,
      capable of inducing inflammation and immunopathology. Thus it may be an important
      target for immunotherapy.

PMID- 17038481
TI  - Targeted therapies: summary clinical trials working group.

PMID- 17038480
TI  - Mitogen activated protein kinase inhibitors: where are we now and where are we
      going?
AB  - Orally bioavailable compounds that target key intracellular signalling molecules
      are receiving increasing attention for the treatment of rheumatic diseases. The
      mitogen activated protein (MAP) kinases are especially attractive because they
      regulate both cytokine production and cytokine action. The MAP kinases are
      expressed and activated in rheumatoid arthritis (RA) synovium. Preclinical
      studies using MAP kinase inhibitors are very effective in animal models of
      arthritis, supporting their potential utility in human disease. Although the
      available data suggest a rationale for MAP kinase blockade, development of drugs
      has been hampered by toxicity and limited efficacy. Alternative strategies, such
      as targeting other kinases in the cascade or development of allosteric inhibitors
      have been proposed. These approaches might permit effective use of MAP kinase
      inhibitors for the treatment of rheumatic and immune-mediated diseases.

PMID- 17038479
TI  - Use of cell permeable NBD peptides for suppression of inflammation.
AB  - Nuclear factor (NF)-kappaB is a ubiquitous and essential transcription factor
      whose dysregulation has been linked to numerous diseases including arthritis and
      cancer. It is therefore not surprising that the NF-kappaB activation pathway has
      become a major target for development of novel therapies for inflammatory
      diseases and cancer. However, the indispensable role played by NF-kappaB in many
      biological processes has raised concern that a complete shutdown of this pathway
      would have significant detrimental effects on normal cellular function. Instead,
      drugs that selectively target the inflammation induced NF-kappaB activity, while
      sparing the protective functions of basal NF-kappaB activity, would be of greater
      therapeutic value and would likely display fewer undesired side effects. The
      recent identification and characterisation of the NF-kappaB essential modulator
      (NEMO)-binding domain (NBD) peptide that can block the activation of the IkappaB
      kinase (IKK) complex, have provided an opportunity to selectively abrogate the
      inflammation induced activation of NF-kappaB by targeting the NBD-NEMO
      interaction. This peptide is synthesised in tandem with a protein transduction
      domain sequence from Drosophila antennapedia which facilitates uptake of the
      inhibitory peptide into the cytosol of target cells.

PMID- 17038482
TI  - Cardiovascular haemodynamics and ventriculo-arterial coupling in an acute pig
      model of coronary ischaemia-reperfusion.
AB  - Although reperfusion after coronary occlusion is mandatory for myocardial
      salvage, reperfusion may trigger a cascade of harmful events (reperfusion injury)
      adding to myocardial injury. We investigated effects of reperfusion on left
      ventricular (LV) haemodynamics and ventriculo-arterial (VA) coupling in pigs
      following acute myocardial ischaemia induced by coronary artery occlusion.
      Experiments were performed in six animals, with measurements of cardiac and
      arterial function at baseline, after 60 min of ischaemia (T60) and after 2 (T180)
      and 4 h of reperfusion (T300). Ventriculo-arterial coupling was assessed using
      the ventriculo-arterial elastance ratio of paper, as well as using a 'stiffness
      coupling' and 'temporal coupling' index. Reperfusion following ischaemia (T180
      versus T60) induced a progressive decline in cardiovascular function, evidenced
      by a decrease in mean arterial blood pressure, cardiac output and ejection
      fraction which was not restored at T300. Although reperfusion also induced an
      increase in slope of the end-systolic pressure-volume relationship (ESPVR), the
      ESPVR curve shifted to the right, associated with a depression of contractile
      function. Histology demonstrated irreversible myocardial damage at T300. The
      ventriculo-arterial elastance ratio and the 'stiffness coupling' index were
      unaffected throughout the protocol, but the 'temporal coupling' parameter
      indicated a relative shift between heart period and the time constant of the
      arterial system. It is unlikely that these alterations are attributable to
      ischaemic injury alone. The combination of both the stiffness and temporal
      coupling index may provide more information when studying ventriculo-arterial
      coupling than the more commonly used ventricular end-systolic stiffness/effection
      arterial elastance (E(es)/E(a)) ratio.

PMID- 17038483
TI  - Obligatory role for complex I inhibition in the dopaminergic neurotoxicity of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
AB  - Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice and
      nonhuman primates causes a parkinsonian disorder characterized by a loss of
      dopamine-producing neurons in the substantia nigra and corresponding motor
      deficits. MPTP has been proposed to exert its neurotoxic effects through a
      variety of mechanisms, including inhibition of complex I of the mitochondrial
      respiratory chain, displacement of dopamine from vesicular stores, and formation
      of reactive oxygen species from mitochondrial or cytosolic sources. However, the
      mechanism of MPTP-induced neurotoxicity is still a matter of debate. Recently, we
      reported that the yeast single-subunit nicotinamide adenine dinucleotide
      (reduced) dehydrogenase (NDI1) is resistant to rotenone, a complex I inhibitor
      that produces a parkinsonian syndrome in rats, and that overexpression of NDI1 in
      SK-N-MC cells prevents the toxicity of rotenone. In this study, we used viral
      mediated overexpression of NDI1 in SK-N-MC cells and animals to determine the
      relative contribution of complex I inhibition in the toxicity of MPTP. In cell
      culture, NDI1 overexpression abolished the toxicity of 1-methyl-4
      phenylpyridinium, the active metabolite of MPTP. Overexpression of NDI1 through
      stereotactic administration of a viral vector harboring the NDI1 gene into the
      substantia nigra protected mice from both the neurochemical and behavioral
      deficits elicited by MPTP. These data identify inhibition of complex I as a
      requirement for dopaminergic neurodegeneration and subsequent behavioral deficits
      produced by MPTP. Furthermore, combined with reports of a complex I defect in
      Parkinson's disease (PD) patients, the present study affirms the utility of MPTP
      in understanding the molecular mechanisms underlying dopaminergic
      neurodegeneration in PD.

PMID- 17038484
TI  - Evidence in favor of the contribution of genes involved in the maintenance of the
      extracellular matrix of the arterial wall to the development of intracranial
      aneurysms.
AB  - Intracranial aneurysm is probably a complex disease with both genetic and non
      genetic or environmental risk factors contributing to the etiology of the
      disease. A disruption of the extracellular matrix (ECM) of the arterial wall is a
      likely factor in the pathogenesis of intracranial aneurysms. We analyzed 44
      potential candidate genes involved in the maintenance of the integrity of the ECM
      in 382 Dutch Caucasian patients with intracranial aneurysms and 609 Dutch
      Caucasian controls for 384 tag single nucleotide polymorphisms (SNPs) using the
      GoldenGate assay on an Illumina BeadStation 500 GX. We identified SNPs that were
      associated with intracranial aneurysms (P<0.01) in six of these 44 genes:
      serpine1 (SERPINE1, P=0.0008), transforming growth factor beta induced (TGFBI,
      P=0.0026), perlecan (HSPG2, P=0.0044), fibronectin (FN1, P=0.0069), fibrillin 2
      (FBN2, P=0.0077) and alpha 1 type IV collagen (COL4A1, P=0.0087). In a second
      independent cohort of 310 Dutch Caucasian intracranial aneurysm patients and 336
      Dutch Caucasian controls, the association for the HSPG2 gene [combined odds ratio
      (OR) 1.33, 95% confidence interval (CI) 1.13-1.57, P=6 x 10(-4)] was replicated.
      The population attributable risk (PAR) for this SNP is 19%. Combining the two
      cohorts still showed association for the SERPINE1 (combined OR 1.27, 95% CI 1.07
      1.50, P=0.004, PAR 6%), FBN2 (combined OR 1.37, 95% CI 1.07-1.75, P=0.01, PAR 3%)
      and COL4A1 (combined OR 1.22, 95% CI 1.05-1.42, P=0.007, PAR 7%) genes. These
      PARs are likely to be overestimates as they are calculated from the joint
      analyses combining stages 1 and 2 of our association study. Our findings indicate
      that variation in genes involved in the maintenance of the integrity of the ECM
      of the arterial wall plays a role in susceptibility to intracranial aneurysms.
      These findings further support our hypothesis that diminished maintenance of the
      ECM of the arterial wall is important in the development of intracranial
      aneurysms.

PMID- 17038485
TI  - Sesn1 is a novel gene for left-right asymmetry and mediating nodal signaling.
AB  - Remarkable progress has been made in understanding the molecular mechanisms
      underlying left-right asymmetry in vertebrate animal models but little is known
      on left-right axis formation in humans. Previously, we identified SESN1 (also
      known as PA26) as a candidate gene for heterotaxia by positional cloning of the
      breakpoint regions of a de novo translocation in a heterotaxia patient. In this
      study, we show by means of a zebrafish sesn1-knockdown model that Sesn1 is
      required for normal embryonic left-right determination. In this model,
      developmental defects and expression data of genes implicated in vertebrate left
      right asymmetry indicate a role for Sesn1 in mediating Nodal signaling. In the
      lateral plate mesoderm, Nodal signaling plays a central role in left-right axis
      formation in vertebrates and is mediated by FoxH1 transcriptional induction. In
      line with this, we show that Sesn1 physically interacts with FoxH1 or a FoxH1
      containing complex. Mutation analysis in a panel of 234 patients with isolated
      heterotaxia did not reveal mutations, indicating that these are only exceptional
      causes of human heterotaxia. In this study, we identify SESN1 as an indispensable
      gene for vertebrate left-right asymmetry and a new player in mediating Nodal
      signaling.

PMID- 17038486
TI  - Sex inequity in tendon metabolism?

PMID- 17038487
TI  - Short-term strength training and the expression of myostatin and IGF-I isoforms
      in rat muscle and tendon: differential effects of specific contraction types.
AB  - In skeletal muscle, an increased expression of insulin like growth factor-I
      isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of
      myostatin is thought to be essential for training-induced hypertrophy. However,
      the specific effects of different contraction types on regulation of these
      factors in muscle are still unclear, and in tendon the functions of myostatin,
      IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats
      were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9
      per group) of the medial gastrocnemius, by stimulation of the sciatic nerve
      during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle
      and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA
      decreased in response to all types of training (2- to 8-fold) (P < 0.05), but the
      effect of eccentric training was greater than concentric and isometric training
      (P < 0.05). In tendon, myostatin mRNA was detected, but no changes were seen
      after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon
      (up to 4-fold) in response to training (P < 0.01). In tendon no difference was
      seen between training types, but in muscle the effect of eccentric training was
      greater than concentric training for both IGF-IEa and MGF (P < 0.05), and for IGF
      IEa isometric training had greater effect than concentric (P < 0.05). The results
      indicate a possible role for IGF-IEa and MGF in adaptation of tendon to training,
      and the combined changes in myostatin and IGF-IEa/MGF expression could explain
      the important effect of eccentric actions for muscle hypertrophy.

PMID- 17038488
TI  - VEGF gradients, receptor activation, and sprout guidance in resting and
      exercising skeletal muscle.
AB  - Extensive experimental studies have identified vascular endothelial growth factor
      (VEGF) concentrations and concentration gradients as major factors in
      angiogenesis; however, localized in vivo measurements of these parameters have
      not been possible. We developed a three-dimensional computational model of
      skeletal muscle fibers, blood vessels, and interstitial space. Here it is applied
      to rat extensor digitorum longus. VEGF isoforms are secreted by myocytes, diffuse
      through extracellular matrix and basement membranes, and bind endothelial cell
      surface receptors on blood vessels. In addition, one isoform, VEGF164, binds to
      proteoglycans in the interstitial space. VEGF secretion rate is determined from
      the predicted tissue oxygen level through its effect on the hypoxia inducible
      factor-1alpha transcription factor. We estimate VEGF secretion and its
      concentrations and gradients in resting muscle and for different levels of
      exercise. The effects of low levels of inspired oxygen are also studied. We
      predict that the high spatial heterogeneity of muscle fiber VEGF secretion in
      hypoxic tissue leads to significant gradients of VEGF concentration and VEGF
      receptor activation. VEGF concentration gradients are predicted to be significant
      in both resting and exercising muscle (4% and 6-8% change in VEGF over 10 microm,
      respectively), sufficient for chemotactic guidance of 50-microm-long sprout tip
      cells. VEGF gradients also result in heterogeneity in VEGF receptor activation--a
      possible explanation for the stochasticity of sprout location. In the absence of
      interstitial flow, gradients are 10-fold steeper in the transverse direction
      (i.e., perpendicular to the muscle fibers) than in the longitudinal direction.
      This may explain observed perpendicular anastomoses in skeletal muscle.

PMID- 17038489
TI  - The effect of running, strength, and vibration strength training on the
      mechanical, morphological, and biochemical properties of the Achilles tendon in
      rats.
AB  - Compared with muscle or bone, there is a lack of information about the
      relationship between tendon adaptation and the applied loading characteristic.
      The purpose of the present study was to analyze the effect of different exercise
      modes characterized by very distinct loading patterns on the mechanical,
      morphological, and biochemical properties of the Achilles tendon. Sixty-four
      female Sprague-Dawley rats were divided into five groups: nonactive age-matched
      control (AMC; n = 20), voluntary wheel running (RT; n = 20), vibration strength
      trained (LVST; n = 12), high-vibration strength-trained (HVST; n = 6), and high
      strength-trained (HST; n = 6) group. After a 12-wk-long experimental period, the
      Achilles tendon was tested mechanically and the cross-sectional area, the soleus
      and gastrocnemius muscle mass, and mRNA concentration of collagen I, collagen
      III, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor
      beta, connective tissue growth factor, and matrix metalloproteinase-2 was
      determined. Neither in the LVST nor in the HVST group could any adaptation of the
      Achilles tendon be detected, although the training had an effect on the
      gastrocnemius muscle mass in the LVST group (P < 0.05). In the HST group, the
      highest creep was found, but the effect was more pronounced compared with the
      LVST group (P < 0.05) than with the AMC group. That indicates that this was
      rather induced by the low muscle mass rather than by training. However, the RT
      group had a higher TIMP-1 mRNA concentration in the Achilles tendon in contrast
      to AMC group (P < 0.05), which suggests that this exercise mode may have an
      influence on tendon adaptation.

PMID- 17038490
TI  - Visualizing lung function with positron emission tomography.
AB  - Positron emission tomography (PET) provides three-dimensional images of the
      distributions of radionuclides that have been inhaled or injected into the lungs.
      By using radionuclides with short half-lives, the radiation exposure of the
      subject can be kept small. By following the evolution of the distributions of
      radionuclides in gases or compounds that participate in lung function,
      information about such diverse lung functions as regional ventilation, perfusion,
      shunt, gas fraction, capillary permeability, inflammation, and gene expression
      can be inferred. Thus PET has the potential to provide information about the
      links between cellular function and whole lung function in vivo. In this paper,
      recent advancements in PET methodology and techniques and information about lung
      function that have been obtained with these techniques are reviewed.

PMID- 17038491
TI  - Effect of long-term muscle paralysis on human single fiber mechanics.
AB  - This study compared human muscles following long-term reduced neuromuscular
      activity to those with normal functioning regarding single fiber properties.
      Biopsies were obtained from the vastus lateralis of 5 individuals with chronic
      (>3 yr) spinal cord injury (SCI) and 10 able-bodied controls (CTRL). Chemically
      skinned fibers were tested for active and passive mechanical characteristics and
      subsequently classified according to myosin heavy chain (MHC) content. SCI
      individuals had smaller proportions of type I (11 +/- 7 vs. 34 +/- 5%) and IIa
      fibers (11 +/- 6 vs. 31 +/- 5%), whereas type IIx fibers were more frequent (40
      +/- 13 vs. 7 +/- 3%) compared with CTRL subjects (P < 0.05). Cross-sectional area
      and peak force were similar in both groups for all fiber types. Unloaded
      shortening velocity of fibers from paralyzed muscles was higher in type IIa,
      IIa/IIx, and IIx fibers (26, 65, and 47%, respectively; P < 0.01). Consequently,
      absolute peak power was greater in type IIa (46%; P < 0.05) and IIa/IIx fibers
      (118%; P < 0.01) of the SCI group, whereas normalized peak power was higher in
      type IIa/IIx fibers (71%; P < 0.001). Ca(2+) sensitivity and passive fiber
      characteristics were not different between the two groups in any fiber type.
      Composite values (average value across all fibers analyzed within each study
      participant) showed similar results for cross-sectional area and peak force,
      whereas maximal contraction velocity and fiber power were more than 100% greater
      in SCI individuals. These data illustrate that contractile performance is
      preserved or even higher in the remaining fibers of human muscles following
      reduced neuromuscular activity.

PMID- 17038492
TI  - Muscle pain induces task-dependent changes in cervical agonist/antagonist
      activity.
AB  - This study examined the effect of experimental neck muscle pain on the EMG-force
      relationship of cervical agonist and antagonist muscles. Surface EMG signals were
      detected from the sternomastoid, splenius capitis, and upper trapezius muscles
      bilaterally from 14 healthy subjects during cervical flexion and extension
      contractions of linearly increasing force from 0 to 60% of the maximum voluntary
      contraction (MVC). Measurements were performed before and after injection of 0.5
      ml hypertonic and isotonic saline into either the sternomastoid or splenius
      capitis in two experimental sessions. EMG average rectified value (ARV) of the
      sternomastoid, splenius capitis, and upper trapezius muscles and the muscle fiber
      conduction velocity (CV) of the sternomastoid muscle were estimated at 5% MVC
      force increments. During cervical flexion with injection of hypertonic saline in
      sternomastoid, ARV of sternomastoid was lower on the side of pain in the force
      range 25-60% MVC (P < 0.05) and was associated with a bilateral reduction of
      splenius capitis and upper trapezius ARV (P < 0.01). During cervical extension,
      injection of hypertonic saline in splenius capitis resulted in lower estimates of
      splenius capitis ARV on the painful side from 45 to 60% MVC (P < 0.05), which was
      associated with a bilateral increase in upper trapezius ARV estimates from 50 to
      60% MVC (P < 0.001). However, no significant change was identified for estimates
      of sternomastoid ARV. Experimentally induced neck muscle pain resulted in task
      dependent changes in cervical agonist/antagonist activity without modifications
      in muscle fiber CV.

PMID- 17038493
TI  - Imaging of the pulmonary circulation in the closed-chest rat using synchrotron
      radiation microangiography.
AB  - Structural changes of the pulmonary circulation during the pathogenesis of
      pulmonary arterial hypertension remain to be fully elucidated. Although
      angiography has been used for visualizing the pulmonary circulation, conventional
      angiography systems have considerable limitations for visualizing small
      microvessels (diameters < 200 microm), particularly within a closed-chest animal
      model. In this study we assess the effectiveness of monochromatic synchrotron
      radiation (SR) for microangiography of the pulmonary circulation in the intact
      chest rat. Male adult Sprague-Dawley rats were anesthetized, and a catheter was
      positioned within the right ventricle, for administering iodinated contrast agent
      (Iomeron 350). Subsequently, microangiography of pulmonary arterial branches
      within the left lung was performed using monochromatic SR. Additionally, we
      assessed dynamic changes in vessel diameter during acute hypoxic (10% and 8% O2
      for 4 min each) pulmonary vasoconstriction (HPV). Using SR we were able to
      visualize pulmonary microvessels with a diameter of <100 microm (the 4th
      generation of branching from the left axial artery). Acute hypoxia caused a
      significant decrease in the diameter of all vessels less than 500 microm. The
      greatest degree of pulmonary vasoconstriction was observed in vessels with a
      diameter between 200 and 300 microm. These results demonstrate the effectiveness
      of SR for visualizing pulmonary vessels in a closed-chest rat model and for
      assessing dynamic changes associated with HPV. More importantly, these
      observations implicate SR as an effective tool in future research for assessing
      gross structural changes associated with the pathogenesis of pulmonary arterial
      hypertension.

PMID- 17038494
TI  - ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and
      extracellular matrix expression in rat pulmonary arterial smooth muscle cells.
AB  - Atrial natriuretic peptide (ANP) and transforming growth factor (TGF)-beta play
      important counterregulatory roles in pulmonary vascular adaptation to chronic
      hypoxia. To define the molecular mechanism of this important interaction, we
      tested whether ANP-cGMP-protein kinase G (PKG) signaling inhibits TGF-beta1
      induced extracellular matrix (ECM) expression and defined the specific site(s) at
      which this molecular merging of signaling pathways occurs. Rat pulmonary arterial
      smooth muscle cells (PASMCs) were treated with ANP (1 muM) or cGMP (1 mM) with or
      without pretreatment with PKG inhibitors KT-5823 (1 muM) or Rp-8-bromo-cGMP (Rp-8
      Br-cGMP 50 muM), then exposed to TGF-beta1 (1 ng/ml) for 5-360 min (for pSmad
      nuclear translocation and protein analysis) or 24 h (for ECM mRNA expression).
      Nuclear translocation of pSmad2 and pSmad3 was assessed by fluorescent confocal
      microscopy. ANP and cGMP inhibited TGF-beta1-induced pSmad2 and pSmad3 nuclear
      translocation and expression of periostin, osteopontin, and plasminogen activator
      inhibitor-1 mRNA and protein, but not TGF-beta1-induced phosphorylation of Smad2
      and Smad3. KT-5823 and Rp-8-Br-cGMP blocked ANP/cGMP-induced activation of PKG
      and inhibition of TGF-beta1-stimulated nuclear translocation of pSmad2 and pSmad3
      in PASMCs. These results reveal for the first time a precise site at which ANP
      cGMP-PKG signaling exerts its antifibrogenic effect on the profibrogenic TGF
      beta1 signaling pathway: by blocking TGF-beta1-induced pSmad2 and pSmad3 nuclear
      translocation and ECM expression in PASMCs. Blocking nuclear translocation and
      subsequent binding of pSmad2 and pSmad3 to TGF-beta-Smad response elements in ECM
      genes may be responsible for the inhibitory effects of ANP on TGF-beta-induced
      expression of ECM molecules.

PMID- 17038495
TI  - Hydrogen sulfide and its possible roles in myocardial ischemia in experimental
      rats.
AB  - The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been
      previously studied. We therefore investigated the effect of H(2)S in a rat model
      of MI in vivo. Animals were randomly divided into three groups (n = 80) and
      received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50
      mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment
      was continued for a further 2 days after MI when the animals were killed. The
      mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS
      treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle
      treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P <
      0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased
      after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e.,
      38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was
      abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further
      showed for the first time cystathionine-gamma-lyase protein localization in the
      myocardium of the infarct area by using immunohistochemical staining. In the
      hypoxic vascular smooth muscle cells, we found that cell death was increased
      under the stimuli of hypoxia but that the increased cell death was attenuated by
      the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/
      2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was
      cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production
      after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S
      might provide a novel approach to the treatment of MI.

PMID- 17038496
TI  - Differences in potential for amino acid change after mutation reveals distinct
      strategies for kappa and lambda light-chain variation.
AB  - B cells generate varied yet functional clones under high rates of mutation of
      their V genes. It has been proposed that as a result of the opposing demands of
      diversification and preservation of integrity, the V genes of heavy and light
      chains have evolved to overexpress codons prone to amino acid change in their
      complementarity determining regions (CDR) compared with the framework (FW)
      regions. We have analyzed the germ-line V genes of heavy and light chains (both
      kappa and lambda), comparing codons of CDR and FW of the germ-line V regions both
      to each other and to control regions. We found that in both germ-line heavy
      chains and lambda chains, CDR codons are prone to replacement mutations, whereas
      in the FW, the opposite is true. Furthermore, the difference between CDR and FW
      in heavy chains and lambda chains is based on codons that are prone to
      nonconservative changes of amino acid. In contrast, in germ-line kappa chains,
      the codons in both CDR and FW are more prone to replacement mutations. We also
      demonstrated that negative selection during immune responses is more sensitive to
      nonconservative amino acid substitutions than overall amino acid change,
      demonstrating the applicability of our analysis to real-time process of selection
      in the immune system. The differences in germ-line kappa and lambda light chains'
      potential reaction to mutation suggests that via these two differently evolved
      light-chain types, the B cell repertoire encompasses two different strategies to
      balance diversity and stability in an immune response.

PMID- 17038497
TI  - Structural basis for mRNA and tRNA positioning on the ribosome.
AB  - Protein synthesis requires the accurate positioning of mRNA and tRNA in the
      peptidyl-tRNA site of the ribosome. Here we describe x-ray crystal structures of
      the intact bacterial ribosome from Escherichia coli in a complex with mRNA and
      the anticodon stem-loop of P-site tRNA. At 3.5-A resolution, these structures
      reveal rearrangements in the intact ribosome that clamp P-site tRNA and mRNA on
      the small ribosomal subunit. Binding of the anticodon stem-loop of P-site tRNA to
      the ribosome is sufficient to lock the head of the small ribosomal subunit in a
      single conformation, thereby preventing movement of mRNA and tRNA before mRNA
      decoding.

PMID- 17038498
TI  - Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4
      tetraphosphate (Ap4A) and positron-emission tomography.
AB  - Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)
      monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are
      competitive inhibitors of adenosine diphosphate-induced platelet aggregation,
      which plays a central role in arterial thrombosis and plaque formation. In this
      study, we evaluate the imaging capabilities of positron-emission tomography (PET)
      with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)
      tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New
      Zealand White rabbits. Three to six months after balloon injury to the aorta, the
      rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid
      accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta,
      with lesions clearly visible 30 min after injection. Computed tomographic images
      were coregistered with PET images to improve delineation of aortoiliac tracer
      activity. Plaque macrophage density, quantified by immunostaining with RAM11
      against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA
      uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by
      immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution
      studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine
      dinucleotide behavior with insignificant myocardial uptake and fast kidney
      clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich
      atherosclerotic plaques can be quantified noninvasively with PET. Hence,
      [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular
      inflammation.

PMID- 17038499
TI  - Branch-cut singularities in thermodynamics of Fermi liquid systems.
AB  - The recently measured spin susceptibility of the two-dimensional electron gas
      exhibits a strong dependence on temperature, which is incompatible with the
      standard Fermi liquid phenomenology. In this article, we show that the observed
      temperature behavior is inherent to ballistic two-dimensional electrons. Besides
      the single-particle and collective excitations, the thermodynamics of Fermi
      liquid systems includes effects of the branch-cut singularities originating from
      the edges of the continuum of pairs of quasiparticles. As a result of the
      rescattering induced by interactions, the branch-cut singularities generate
      nonanalyticities in the thermodynamic potential that reveal themselves in
      anomalous temperature dependences. Calculation of the spin susceptibility in such
      a situation requires a nonperturbative treatment of the interactions. As in high
      energy physics, a mixture of the collective excitations and pairs of
      quasiparticles can effectively be described by a pole in the complex momentum
      plane. This analysis provides a natural explanation for the observed temperature
      dependence of the spin susceptibility, both in sign and in magnitude.

PMID- 17038500
TI  - Ultrashort antibacterial and antifungal lipopeptides.
AB  - Host-defense cationic antimicrobial peptides ( approximately 12-50 aa long) play
      an essential protective role in the innate immune system of all organisms.
      Lipopeptides, however, are produced only in bacteria and fungi during
      cultivation, and they are composed of specific lipophilic moieties attached to
      anionic peptides (six to seven amino acids). Here we report the following. (i)
      The attachment of an aliphatic chain to otherwise inert, cationic D,L
      tetrapeptides endows them with potent activity against various microorganisms
      including antibiotic resistance strains. (ii) Cell specificity is determined by
      the sequence of the short peptidic chain and the length of the aliphatic moiety.
      (iii) Despite the fact that the peptidic chains are very short, their mode of
      action involves permeation and disintegration of membranes, similar to that of
      many long antimicrobial peptides. Besides adding important information on the
      parameters necessary for host-defense lipopeptides to kill microorganisms, the
      simple composition of these lipopeptides and their diverse specificities should
      make them economically available, innate immunity-mimicking antimicrobial and
      antifungal compounds for various applications.

PMID- 17038501
TI  - Generic hydrophobic residues are sufficient to promote aggregation of the
      Alzheimer's Abeta42 peptide.
AB  - One hundred years ago, Alois Alzheimer observed a relationship between cognitive
      impairment and the presence of plaque in the brains of patients suffering from
      the disease that bears his name. The plaque was subsequently shown to be composed
      primarily of a 42-residue peptide called amyloid beta (Abeta) 42. Despite the
      importance of Abeta42 aggregation in the molecular etiology of Alzheimer's
      disease, the amino acid sequence determinants of this process have yet to be
      elucidated. Although stretches of hydrophobic residues in the C-terminal half of
      Abeta42 have been implicated, the mechanism by which these residues promote
      aggregation remains unclear. In particular, it is not known whether the side
      chains of these hydrophobic residues mediate specific interactions that direct
      self-assembly or, alternatively, whether hydrophobicity per se at these positions
      is sufficient to promote aggregation. To distinguish between these two
      possibilities, we substituted 12 hydrophobic residues in the C-terminal half of
      Abeta42 with random nonpolar residues. The mutant sequences were screened by
      using a fusion of Abeta42 to GFP. Because aggregation of Abeta42 prevents folding
      of the GFP reporter, this screen readily distinguishes aggregating from
      nonaggregating variants of Abeta42. Application of the screen demonstrated that,
      despite the presence of 8-12 mutations, all of the sequences aggregated. To
      confirm these results, several of the mutant sequences were prepared as synthetic
      peptides and shown to form amyloid fibrils similar to those of WT Abeta42. These
      findings indicate that hydrophobic stretches in the sequence of Abeta42, rather
      than specific side chains, are sufficient to promote aggregation.

PMID- 17038502
TI  - A tunable algorithm for collective decision-making.
AB  - Complex biological systems are increasingly understood in terms of the algorithms
      that guide the behavior of system components and the information pathways that
      link them. Much attention has been given to robust algorithms, or those that
      allow a system to maintain its functions in the face of internal or external
      perturbations. At the same time, environmental variation imposes a complementary
      need for algorithm versatility, or the ability to alter system function
      adaptively as external circumstances change. An important goal of systems biology
      is thus the identification of biological algorithms that can meet multiple
      challenges rather than being narrowly specified to particular problems. Here we
      show that emigrating colonies of the ant Temnothorax curvispinosus tune the
      parameters of a single decision algorithm to respond adaptively to two distinct
      problems: rapid abandonment of their old nest in a crisis and deliberative
      selection of the best available new home when their old nest is still intact. The
      algorithm uses a stepwise commitment scheme and a quorum rule to integrate
      information gathered by numerous individual ants visiting several candidate
      homes. By varying the rates at which they search for and accept these candidates,
      the ants yield a colony-level response that adaptively emphasizes either speed or
      accuracy. We propose such general but tunable algorithms as a design feature of
      complex systems, each algorithm providing elegant solutions to a wide range of
      problems.

PMID- 17038503
TI  - Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted
      Rag2-/-gamma c-/- mice.
AB  - Because of species selectivity, HIV research is largely restricted to in vitro or
      clinical studies, both limited in their ability to rapidly assess new strategies
      to fight the virus. To prospectively study some aspects of HIV in vivo,
      immunodeficient mice, transplanted with either human peripheral blood leukocytes
      or human fetal tissues, have been developed. Although these are susceptible to
      HIV infection, xenoreactivity, and short infection spans, resource and ethical
      constraints, as well as biased HIV coreceptor tropic strain infection, pose
      substantial problems in their use. Rag2(-/-)gamma(c)(-/-) mice, transplanted as
      newborns with human CD34(+) cells, were recently shown to develop human B, T, and
      dendritic cells, constituting lymphoid organs in situ. Here we tested these mice
      as a model system for HIV-1 infection. HIV RNA levels peaked to up to 2 x 10(6)
      copies per milliliter of plasma early after infection, and viremia was observed
      for up to 190 days, the longest time followed. A marked relative CD4(+) T cell
      depletion in peripheral blood occurred in CXCR4-tropic strain-infected mice,
      whereas this was less pronounced in CCR5-tropic strain-infected animals. Thymus
      infection was almost exclusively observed in CXCR4-tropic strain-infected mice,
      whereas spleen and lymph node HIV infection occurred irrespective of coreceptor
      selectivity, consistent with respective coreceptor expression on human CD4(+) T
      cells. Thus, this straightforward to generate and cost-effective in vivo model
      closely resembles HIV infection in man and therefore should be valuable to study
      virus-induced pathology and to rapidly evaluate new approaches aiming to prevent
      or treat HIV infection.

PMID- 17038504
TI  - Characterization of the nanoscale properties of individual amyloid fibrils.
AB  - We report the detailed mechanical characterization of individual amyloid fibrils
      by atomic force microscopy and spectroscopy. These self-assembling materials,
      formed here from the protein insulin, were shown to have a strength of 0.6 +/-
      0.4 GPa, comparable to that of steel (0.6-1.8 GPa), and a mechanical stiffness,
      as measured by Young's modulus, of 3.3 +/- 0.4 GPa, comparable to that of silk (1
      10 GPa). The values of these parameters reveal that the fibrils possess
      properties that make these structures highly attractive for future technological
      applications. In addition, analysis of the solution-state growth kinetics
      indicated a breakage rate constant of 1.7 +/- 1.3 x 10(-8) s(-1), which reveals
      that a fibril 10 mum in length breaks spontaneously on average every 47 min,
      suggesting that internal fracturing is likely to be of fundamental importance in
      the proliferation of amyloid fibrils and therefore for understanding the
      progression of their associated pathogenic disorders.

PMID- 17038505
TI  - Direct magnetic resonance detection of neuronal electrical activity.
AB  - Present noninvasive neuroimaging methods measure neuronal activity indirectly,
      via either cerebrovascular changes or extracranial measurements of
      electrical/magnetic signals. Recent studies have shown evidence that MRI may be
      used to directly and noninvasively map electrical activity associated with human
      brain activation, but results are inconclusive. Here, we show that MRI can detect
      cortical electrical activity directly. We use organotypic rat-brain cultures in
      vitro that are spontaneously active in the absence of a cerebrovascular system.
      Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly
      correlated with multisite extracellular local field potential recordings of the
      same cultures before and after blockade of neuronal activity with tetrodotoxin.
      Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels
      containing the culture, thus allowing the spatial localization of the active
      neuronal tissue.

PMID- 17038506
TI  - Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell
      differentiation and nuage/germinal granule formation in mice.
AB  - Embryonic patterning and germ-cell specification in mice are regulative and
      depend on zygotic gene activities. However, there are mouse homologues of
      Drosophila maternal effect genes, including vasa and tudor, that function in
      posterior and germ-cell determination. We report here that a targeted mutation in
      Tudor domain containing 1/mouse tudor repeat 1 (Tdrd1/Mtr-1), a tudor-related
      gene in mice, leads to male sterility because of postnatal spermatogenic defects.
      TDRD1/MTR-1 predominantly localizes to nuage/germinal granules, an evolutionarily
      conserved structure in the germ line, and its intracellular localization is
      downstream of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), similar to
      Drosophila vasa-tudor. Tdrd1/Mtr-1 mutants lack, and Mvh/Ddx4 mutants show,
      strong reduction of intermitochondrial cement, a form of nuage in both male and
      female germ cells, whereas chromatoid bodies, another specialized form of nuage
      in spermatogenic cells, are observed in Tdrd1/Mtr-1 mutants. Hence,
      intermitochondrial cement is not a direct prerequisite for oocyte development and
      fertility in mice, indicating differing requirements for nuage and/or its
      components between male and female germ cells. The result also proposes that
      chromatoid bodies likely have an origin independent of or additional to
      intermitochondrial cement. The analogy between Mvh-Tdrd1 in mouse spermatogenic
      cells and vasa-tudor in Drosophila oocytes suggests that this molecular pathway
      retains an essential role(s) that functions in divergent species and in different
      stages/sexes of the germ line.

PMID- 17038507
TI  - Pharmacologic characterization of the cloned human trace amine-associated
      receptor1 (TAAR1) and evidence for species differences with the rat TAAR1.
AB  - The hemagglutinin-tagged human trace amine-associated receptor1 (TAAR1) was
      stably coexpressed with rat Galpha(s) in the AV12-664 cell line, and receptor
      activation was measured as the stimulation of cAMP formation. After blockade of
      endogenously expressed alpha2- and beta-adrenoceptors with 2-[2-(2-methoxy-1,4
      benzodioxanyl)]-imidazoline hydrochloride (2-methoxyidazoxan, RX821002) and
      alprenolol, respectively, the resulting pharmacology was consistent with that of
      a unique receptor subtype. beta-Phenylethylamine (beta-PEA), the putative
      endogenous ligand, gave an EC50 of 106 +/- 5 nM in the assay. For a series of
      beta-PEA analogs used to explore the pharmacophore, small substituents at ring
      positions 3 and/or 4 generally resulted in compounds having lower potency than
      beta-PEA, although several were as potent as beta-PEA. However, small
      substituents at ring position 2 resulted in a number of compounds having
      potencies as good as or better than beta-PEA. A number of nonselective
      antagonists known to share affinity for multiple monoaminergic receptors were
      evaluated for their ability to inhibit beta-PEA stimulation of the human TAAR1.
      None had an IC50 <10 microM. For comparison, the rat TAAR1 receptor was expressed
      in the AV12-664 cell line. A number of agonist compounds had significantly
      different relative potencies between the rat and human TAAR1, demonstrating a
      significant species difference between the rat and human TAAR1. The TAAR1
      receptor exhibits a pharmacologic profile uniquely different from those of
      classic monoaminergic receptors, consistent with the structural information that
      places them in a distinct family of receptors. This unique pharmacologic profile
      suggests the potential for development of TAAR-selective agonists and antagonists
      to study their physiologic roles.

PMID- 17038508
TI  - Marked strain differences in the pharmacokinetics of an alpha4beta1 integrin
      antagonist, 4-[1-[3-Chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro
      (2S)-pyrrolidine-2-yl]-methoxybenzoic Acid (D01-4582), in Sprague-Dawley rats are
      associated with albumin genetic polymorphism.
AB  - Strain differences in pharmacokinetics of an alpha4beta1 integrin antagonist, 4
      [1-[3-chloro-4-[N-(2-methylphenyl)-ureido]phenylacetyl]-(4S)-fluoro-(2S)
      pyrrolidine-2-yl]methoxybenzoic acid (D01-4582), in Sprague-Dawley rat strains
      (SD rat and CD rat) and their mechanism were investigated. Total plasma
      clearances of D01-4582 were 31.5 and 5.23 ml/min/kg in SD and CD rats,
      respectively. From in vivo studies, hepatic uptake process was thought to be
      involved in the strain differences. Differences in the uptake of D01-4582 by
      isolated hepatocytes prepared from the both strains were not observed when
      hepatocytes were incubated with simple buffer, but marked differences were
      observed when hepatocytes were incubated with plasma. When the dissociation
      constants (Kd) for the plasma protein binding of D01-4582 were examined in six
      rat strains, each strain was classified into two groups: a high-Kd group, which
      included SD rats, Brown Norway rats, and Wistar rats; and a low-Kd group, which
      included CD rats, Lewis rats, and Eisai hyperbilirubinemic rats. Since all rat
      strains in the low-Kd group showed higher area under the concentration-time curve
      for D01-4582 than rats in the high-Kd group, it was considered that the strain
      differences in the pharmacokinetics of D01-4582 were due to differences in the
      binding affinity. Purified albumin also showed strain differences in Kd. The cDNA
      sequence of the albumin was analyzed, and 11 substitutions were observed. V238L
      and T293I were found only in the high-Kd group, suggesting that these amino acid
      changes reduced the binding affinity of albumin for D01-4582. In conclusion, the
      strain differences in D01-4582 pharmacokinetics were suggested to be caused by an
      alteration in Kd, associated with albumin genetic polymorphism.

PMID- 17038509
TI  - Bias in estimation of transporter kinetic parameters from overexpression systems:
      Interplay of transporter expression level and substrate affinity.
AB  - The objective was to investigate the interplay between transporter expression
      levels and substrate affinity in controlling the influence of aqueous boundary
      layer (ABL) resistance on transporter kinetics in an over-expression system.
      Taurocholate flux was measured across human apical sodium-dependent bile acid
      transporter (hASBT)-Madin-Darby canine kidney monolayers on different occasions
      and kinetic parameters estimated with and without considering ABL. In error-free
      simulation/regression studies, flux values were generated across a range of J
      max, Kt, and substrate concentrations. Similar evaluation was performed for
      transport inhibition studies. Additionally, simulation/regression studies were
      performed, incorporating 15% random error to estimate the probability of
      successfully estimating Kt. Across different occasions, experimental J max and Kt
      estimates for taurocholate were strongly associated (p < 0.001; r2 = 0.82) when
      ABL was not considered. Simulation/regression results indicate that not
      considering ABL caused this association, such that Kt estimates were highly
      positively biased at high hASBT expression. In reanalyzing taurocholate flux data
      using the ABL-present model, Kt was relatively constant across occasions
      (approximately 5 microM) and not associated with J max (p = 0.24; r2 = 0.13).
      Simulations suggest that J max and Kt collectively determined ABL influence,
      which is most prominent under conditions of low monolayer resistance.
      Additionally, not considering ABL lead to negatively biased Ki estimates,
      especially at high J max. Error-inclusive simulation/regression studies indicated
      that the probability of successfully estimating Kt depended on the contribution
      of ABL resistance to flux; when flux became increasingly ABL-limited, probability
      of success decreased. Results indicate that ABL resistance can bias Kt and Ki
      estimates from overexpression systems, where the extent of bias is determined by
      transporter expression level and substrate affinity.

PMID- 17038510
TI  - Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors
      or specific inhibitor lactacystin leads to a defect in adipogenesis, which
      involves matrix metalloproteinase-9.
AB  - In a previous publication, we reported that human immunodeficiency virus (HIV)
      protease inhibitors (PIs) inhibited the differentiation of human preadipocytes in
      primary culture, reducing the expression and secretion of matrix
      metalloproteinase 9 (MMP-9). The present work was performed to clarify this
      mechanism. Interestingly, HIV-PIs have been reported to be inhibitors of the
      proteasome complex, which is known to regulate nuclear factor (NF)-kappaB
      activation and transcription of its target genes, among them MMP-9. We thus
      investigated the potential involvement of the proteasome in the antiadipogenic
      effects of HIV-PIs. The effect of four HIV-PIs was tested on preadipocyte
      proteasomal activity, and chronic treatment with the specific proteasome
      inhibitor lactacystin was performed to evaluate alterations of adipogenesis and
      MMP-9 expression/secretion. Finally, modifications of the NF-kappaB pathway
      induced by either HIV-PIs or lactacystin were studied. We demonstrated that
      preadipocyte proteasomal activity was decreased by several HIV-PIs and that
      chronic treatment with lactacystin mimicked the effects of HIV-PIs by reducing
      adipogenesis and MMP-9 expression/secretion. Furthermore, we observed an
      intracellular accumulation of the NF-kappaB inhibitor, IkappaBbeta, with chronic
      treatment with HIV-PIs or lactacystin as well as a decrease in MMP-9 expression
      induced by acute tumor necrosis factor-alpha stimulation. These results indicate
      that inhibition of the proteasome by specific (lactacystin) or nonspecific (HIV
      PIs) inhibitors leads to a reduction of human adipogenesis, and they therefore
      implicate deregulation of the NF-kappaB pathway and the related decrease of the
      key adipogenic factor, MMP-9. This study adds significantly to recent reports
      that have linked HIV-PI-related lipodystrophic syndrome with altered proteasome
      function, endoplasmic reticulum stress, and metabolic disorders.

PMID- 17038511
TI  - Desoxyrhaponticin (3,5-dihydroxy-4'-methoxystilbene 3-O-beta-D-glucoside)
      inhibits glucose uptake in the intestine and kidney: In vitro and in vivo
      studies.
AB  - Rhubarb extracts have been reported to improve oral glucose tolerance in diabetic
      animals. In the present study we have investigated the antidiabetic actions of
      desoxyrhaponticin, a major stilbene in rhubarb, as a glucose uptake inhibitor.
      Desoxyrhaponticin was demonstrated to inhibit glucose uptake in rabbit intestinal
      membrane vesicles as well as in rat everted gut sleeves, with IC50 values of
      148.3 and 30.9 microM, respectively. Kinetics studies revealed that
      desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems.
      Moreover, desoxyrhaponticin could reduce glucose uptake in the intestinal
      membrane vesicles of both normal and diabetic rats. In addition, glucose uptake
      in the renal membrane vesicles of both normal and diabetic rats was reduced by
      desoxyrhaponticin. Under the inhibition of desoxyrhaponticin, uptake of glucose
      in both the intestinal and renal membrane vesicles of the normal rats was no
      different from that of the diabetic rats. The IC50 values of the uptake
      inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8
      and 115.7 microM, respectively. In a type 2 diabetic animal model in which rats
      have been treated with streptozotocin at the neonatal stage, postprandial
      hyperglycemia was significantly suppressed by oral administration of this
      compound (300 mg/kg b.wt.). These results suggest that desoxyrhaponticin is an
      agent that is potentially effective in controlling postprandial hyperglycemia in
      diabetes. The in vivo antidiabetic action of this compound can be explained, in
      part at least, by inhibition of glucose transport in the small intestine and
      inhibition of glucose reabsorption in the kidney.

PMID- 17038512
TI  - WAY-163909 [(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta
      [b][1,4]diazepino[6,7,1hi]indole]: A novel 5-hydroxytryptamine 2C receptor
      selective agonist with preclinical antipsychotic-like activity.
AB  - Serotonin-2C (5-HT2C) receptor antagonists and agonists have been shown to affect
      dopamine (DA) neurotransmission, with agonists selectively decreasing mesolimbic
      DA. As antipsychotic efficacy is proposed to be associated with decreased
      mesolimbic DA neurotransmission by virtue of DA D2 receptor antagonism, the 5
      HT2C-selective receptor agonist, WAY-163909 [(7bR,10aR)-1,2, 3,4,8,9,10,10a
      octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole], was evaluated in
      animal models of schizophrenia and in vivo microdialysis and electrophysiology to
      determine the effects on mesolimbic and nigrostriatal DA neurotransmission.
      Similar to clozapine, WAY-163909 (1.7-30 mg/kg i.p.) decreased apomorphine
      induced climbing with little effect on stereotypy and no significant induction of
      catalepsy. WAY-163909 (0.3-3 mg/kg s.c.) more potently reduced phencyclidine
      induced locomotor activity compared with d-amphetamine with no effect on
      spontaneous activity. WAY-163909 (1.7-17 mg/kg i.p.) reversed MK-801 (5H
      dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)- and DOI [1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane]-disrupted prepulse inhibition of startle
      (PPI) and improved PPI in DBA/2N mice. In conditioned avoidance responding, WAY
      163909 (0.3-3 mg/kg i.p.; 1-17 mg/kg p.o.) reduced avoidance responding, an
      effect blocked by the 5-HT(2B/2C) receptor antagonist SB 206553 [5-methyl-1-(3
      pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole]. WAY-163909 (10 mg/kg
      s.c.) selectively decreased extracellular levels of DA in the nucleus accumbens
      without affecting the striatum. Likewise, in vivo electrophysiological recordings
      showed a decrease in the number of spontaneously firing DA neurons in the ventral
      tegmental area but not in the substantia nigra with both acute and chronic (21
      day) administration of WAY-163909 (1-10 mg/kg i.p.). Thus, the profile of the 5
      HT2C selective receptor agonist WAY-163909 is similar to that of an atypical
      antipsychotic and additionally may have rapid onset properties.

PMID- 17038513
TI  - Repression of mesodermal fate by foxa, a key endoderm regulator of the sea urchin
      embryo.
AB  - The foxa gene is an integral component of the endoderm specification subcircuit
      of the endomesoderm gene regulatory network in the Strongylocentrotus purpuratus
      embryo. Its transcripts become confined to veg2, then veg1 endodermal
      territories, and, following gastrulation, throughout the gut. It is also
      expressed in the stomodeal ectoderm. gatae and otx genes provide input into the
      pregastrular regulatory system of foxa, and Foxa represses its own transcription,
      resulting in an oscillatory temporal expression profile. Here, we report three
      separate essential functions of the foxa gene: it represses mesodermal fate in
      the veg2 endomesoderm; it is required in postgastrular development for the
      expression of gut-specific genes; and it is necessary for stomodaeum formation.
      If its expression is reduced by a morpholino, more endomesoderm cells become
      pigment and other mesenchymal cell types, less gut is specified, and the larva
      has no mouth. Experiments in which blastomere transplantation is combined with
      foxa MASO treatment demonstrate that, in the normal endoderm, a crucial role of
      Foxa is to repress gcm expression in response to a Notch signal, and hence to
      repress mesodermal fate. Chimeric recombination experiments in which veg2, veg1
      or ectoderm cells contained foxa MASO show which region of foxa expression
      controls each of the three functions. These experiments show that the foxa gene
      is a component of three distinct embryonic gene regulatory networks.

PMID- 17038514
TI  - The allantois and chorion, when isolated before circulation or chorio-allantoic
      fusion, have hematopoietic potential.
AB  - The chorio-allantoic placenta forms through the fusion of the allantois
      (progenitor tissue of the umbilical cord), with the chorionic plate. The murine
      placenta contains high levels of hematopoietic stem cells, and is therefore a
      stem cell niche. However, it is not known whether the placenta is a site of
      hematopoietic cell emergence, or whether hematopoietic cells originate from other
      sites in the conceptus and then colonize the placenta. Here, we show that the
      allantois and chorion, isolated prior to the establishment of circulation, have
      the potential to give rise to myeloid and definitive erythroid cells following
      explant culture. We further show that the hematopoietic potential of the
      allantois and chorion does not require their union, indicating that it is an
      intrinsic property of these tissues. These results suggest that the placenta is
      not only a niche for, but also a source of, hematopoietic cells.

PMID- 17038515
TI  - her5 expression reveals a pool of neural stem cells in the adult zebrafish
      midbrain.
AB  - Current models of vertebrate adult neural stem cells are largely restricted to
      the rodent forebrain. To extract the general mechanisms of neural stem cell
      biology, we sought to identify new adult stem cell populations, in other model
      systems and/or brain areas. The teleost zebrafish appears to be an ideal system,
      as cell proliferation in the adult zebrafish brain is found in many more niches
      than in the mammalian brain. As a starting point towards identifying stem cell
      populations in this system, we used an embryonic neural stem cell marker, the
      E(spl) bHLH transcription factor Her5. We demonstrate that her5 expression is not
      restricted to embryonic neural progenitors, but also defines in the adult
      zebrafish brain a new proliferation zone at the junction between the mid- and
      hindbrain. We show that adult her5-expressing cells proliferate slowly, self
      renew and express neural stem cell markers. Finally, using in vivo lineage
      tracing in her5:gfp transgenic animals, we demonstrate that the her5-positive
      population is multipotent, giving rise in situ to differentiated neurons and glia
      that populate the basal midbrain. Our findings conclusively identify a new
      population of adult neural stem cells, as well as their fate and their endogenous
      environment, in the intact vertebrate brain. This cell population, located
      outside the forebrain, provides a powerful model to assess the general mechanisms
      of vertebrate neural stem cell biology. In addition, the first transcription
      factor characteristic of this cell population, Her5, points to the E(Spl) as a
      promising family of candidate adult neural stem cell regulators.

PMID- 17038516
TI  - LONGIFOLIA1 and LONGIFOLIA2, two homologous genes, regulate longitudinal cell
      elongation in Arabidopsis.
AB  - Plants have diversified their leaf morphologies to adapt to diverse ecological
      niches. The molecular components responsible for regulating leaf morphology,
      however, have not been fully elucidated. By screening Arabidopsis activation
      tagging lines, we identified a dominant mutant, which we designated longifolia1
      1D (lng1-1D). lng1-1D plants were characterized by long petioles, narrow but
      extremely long leaf blades with serrated margins, elongated floral organs, and
      elongated siliques. The elongated leaves of the mutant were due to increased
      polar cell elongation rather than increased cell proliferation. Molecular
      characterization revealed that this phenotype was caused by overexpression of the
      novel gene LNG1, which was found to have a homolog, LNG2,in Arabidopsis. To
      further examine the role of the LNG genes, we characterized lng1 and lng2 loss-of
      function mutant lines. In contrast to the elongated leaves of lng1-1D plants, the
      lng1 and lng2 mutants showed slightly decreased leaf length. Furthermore, the
      lng1-3 lng2-1 double mutant showed further decreased leaf length associated with
      less longitudinal polar cell elongation. The leaf widths in lng1-3 lng2-1 mutant
      plants were similar to those in wild type, implying that the role of LNG1 and
      LNG2 on polar cell elongation is similar to that of ROTUNDIFOLIA3 (ROT3).
      However, analysis of a lng1-3 lng2-1 rot3-1 triple mutant and of a lng1-1D rot3-1
      double mutant indicated that LNG1 and LNG2 promote longitudinal cell elongation
      independently of ROT3. Taken together, these findings indicate that LNG1 and LNG2
      are new components that regulate leaf morphology by positively promoting
      longitudinal polar cell elongation independently of ROT3 in Arabidopsis.

PMID- 17038517
TI  - Segment-specific requirements for dorsoventral patterning genes during early
      brain development in Drosophila.
AB  - An initial step in the development of the Drosophila central nervous system is
      the delamination of a stereotype population of neural stem cells (neuroblasts,
      NBs) from the neuroectoderm. Expression of the columnar genes ventral nervous
      system defective (vnd), intermediate neuroblasts defective (ind) and muscle
      segment homeobox (msh) subdivides the truncal neuroectoderm (primordium of the
      ventral nerve cord) into a ventral, intermediate and dorsal longitudinal domain,
      and has been shown to play a key role in the formation and/or specification of
      corresponding NBs. In the procephalic neuroectoderm (pNE, primordium of the
      brain), expression of columnar genes is highly complex and dynamic, and their
      functions during brain development are still unknown. We have investigated the
      role of these genes (with special emphasis on the Nkx2-type homeobox gene vnd) in
      early embryonic development of the brain. We show at the level of individually
      identified cells that vnd controls the formation of ventral brain NBs and is
      required, and to some extent sufficient, for the specification of ventral and
      intermediate pNE and deriving NBs. However, we uncovered significant differences
      in the expression of and regulatory interactions between vnd, ind and msh among
      brain segments, and in comparison to the ventral nerve cord. Whereas in the trunk
      Vnd negatively regulates ind, Vnd does not repress ind (but does repress msh) in
      the ventral pNE and NBs. Instead, in the deutocerebral region, Vnd is required
      for the expression of ind. We also show that, in the anterior brain
      (protocerebrum), normal production of early glial cells is independent from msh
      and vnd, in contrast to the posterior brain (deuto- and tritocerebrum) and to the
      ventral nerve cord.

PMID- 17038518
TI  - The columnar gene vnd is required for tritocerebral neuromere formation during
      embryonic brain development of Drosophila.
AB  - In Drosophila, evolutionarily conserved transcription factors are required for
      the specification of neural lineages along the anteroposterior and dorsoventral
      axes, such as Hox genes for anteroposterior and columnar genes for dorsoventral
      patterning. In this report, we analyse the role of the columnar patterning gene
      ventral nervous system defective (vnd) in embryonic brain development. Expression
      of vnd is observed in specific subsets of cells in all brain neuromeres. Loss-of
      function analysis focussed on the tritocerebrum shows that inactivation of vnd
      results in regionalized axonal patterning defects, which are comparable with the
      brain phenotype caused by mutation of the Hox gene labial (lab). However, in
      contrast to lab activity in specifying tritocerebral neuronal identity, vnd is
      required for the formation and specification of tritocerebral neural lineages.
      Thus, in early vnd mutant embryos, the Tv1-Tv5 neuroblasts, which normally
      express lab, do not form. Later in embryogenesis, vnd mutants show an extensive
      loss of lab-expressing cells because of increased apoptotic activity, resulting
      in a gap-like brain phenotype that is characterized by an almost complete absence
      of the tritocerebral neuromere. Correspondingly, genetic block of apoptosis in
      vnd mutant embryos partially restores tritocerebral cells as well as axon tracts.
      Taken together, our results indicate that vnd is required for the genesis and
      proper identity specification of tritocerebral neural lineages during embryonic
      brain development of Drosophila.

PMID- 17038519
TI  - Nemo-like kinase (NLK) acts downstream of Notch/Delta signalling to downregulate
      TCF during mesoderm induction in the sea urchin embryo.
AB  - Studies in Caenorhabditis elegans and vertebrates have established that the MAP
      kinase-related protein NLK counteracts Wnt signalling by downregulating the
      transcription factor TCF. Here, we present evidence that during early development
      of the sea urchin embryo, NLK is expressed in the mesodermal precursors in
      response to Notch signalling and directs their fate by downregulating TCF. The
      expression pattern of nlk is strikingly similar to that of Delta and the two
      genes regulate the expression of each other. nlk overexpression, like ectopic
      activation of Notch signalling, provoked massive formation of mesoderm and
      associated epithelial mesenchymal transition. NLK function was found to be
      redundant with that of the MAP kinase ERK during mesoderm formation and to
      require the activity of the activating kinase TAK1. In addition, the sea urchin
      NLK, like its vertebrate counterpart, antagonizes the activity of the
      transcription factor TCF. Finally, activating the expression of a TCF-VP16
      construct at blastula stages strongly inhibits endoderm and mesoderm formation,
      indicating that while TCF activity is required early for launching the
      endomesoderm gene regulatory network, it has to be downregulated at blastula
      stage in the mesodermal lineage. Taken together, our results indicate that the
      evolutionarily conserved TAK/NLK regulatory pathway has been recruited downstream
      of the Notch/Delta pathway in the sea urchin to switch off TCF-beta-catenin
      signalling in the mesodermal territory, allowing precursors of this germ layer to
      segregate from the endomesoderm.

PMID- 17038520
TI  - Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at
      fertilization: a role for the MAP kinase pathway.
AB  - A sperm-induced intracellular Ca2+ signal ([Ca2+]i) underlies the initiation of
      embryo development in most species studied to date. The inositol 1,4,5
      trisphosphate receptor type 1 (IP3R1) in mammals, or its homologue in other
      species, is thought to mediate the majority of this Ca2+ release. IP3R1-mediated
      Ca2+ release is regulated during oocyte maturation such that it reaches maximal
      effectiveness at the time of fertilization, which, in mammalian eggs, occurs at
      the metaphase stage of the second meiosis (MII). Consistent with this, the
      [Ca2+]i oscillations associated with fertilization in these species occur most
      prominently during the MII stage. In this study, we have examined the molecular
      underpinnings of IP3R1 function in eggs. Using mouse and Xenopus eggs, we show
      that IP3R1 is phosphorylated during both maturation and the first cell cycle at a
      MPM2-detectable epitope(s), which is known to be a target of kinases controlling
      the cell cycle. In vitro phosphorylation studies reveal that MAPK/ERK2, one of
      the M-phase kinases, phosphorylates IP3R1 at at least one highly conserved site,
      and that its mutation abrogates IP3R1 phosphorylation in this domain. Our studies
      also found that activation of the MAPK/ERK pathway is required for the IP3R1 MPM2
      reactivity observed in mouse eggs, and that eggs deprived of the MAPK/ERK pathway
      during maturation fail to mount normal [Ca2+]i oscillations in response to
      agonists and show compromised IP3R1 function. These findings identify IP3R1
      phosphorylation by M-phase kinases as a regulatory mechanism of IP3R1 function in
      eggs that serves to optimize [Ca2+]i release at fertilization.

PMID- 17038521
TI  - Generation of GABAergic and dopaminergic interneurons from endogenous embryonic
      olfactory bulb precursor cells.
AB  - During the embryonic period, many olfactory bulb (OB) interneurons arise in the
      lateral ganglionic eminence (LGE) from precursor cells expressing Dlx2, Gsh2 and
      Er81 transcription factors. Whether GABAergic and dopaminergic interneurons are
      also generated within the embryonic OB has not been studied thoroughly. In
      contrast to abundant Dlx2 and Gsh2 expression in ganglionic eminences (GE), Dlx2
      and Gsh2 proteins are not expressed in the E12.5-13.5 mouse OB, whereas the
      telencephalic pallial domain marker Pax6 is abundant. We found GABAergic and
      dopaminergic neurons originating from dividing precursor cells in E13.5 OB and in
      short-term dissociated cultures prepared from the rostral half of E13.5 OB. In OB
      cultures, 22% of neurons were GAD+, of which 53% were Dlx2+, whereas none
      expressed Gsh2. By contrast, 70% of GAD+ cells in GE cultures were Dlx2+ and 16%
      expressed Gsh2. In E13.5 OB slices transplanted with EGFP-labeled E13.5 OB
      precursor cells, 31.7% of EGFP+ cells differentiated to GABAergic neurons. OB and
      LGE precursors transplanted into early postnatal OB migrated and differentiated
      in distinct patterns. Transplanted OB precursors gave rise to interneurons with
      dendritic spines in close proximity to synaptophysin-positive boutons.
      Interneurons were also abundant in differentiating OB neural stem cell cultures;
      the neurons responded to the neurotrophin Bdnf and expressed presynaptic
      proteins. In vivo, the Bdnf receptor TrkB colocalized with synaptic proteins at
      the glomeruli. These findings suggest that, in addition to receiving interneurons
      from the LGE, the embryonic OB contains molecularly distinct local precursor
      cells that generate mature GABAergic and dopaminergic neurons.

PMID- 17038522
TI  - Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro
      and in vivo antitumor activities.
AB  - Antigens expressed on malignant cells in the absence of significant expression on
      normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a
      TNF superfamily member whose normal expression is highly restricted but is
      aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma
      (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as
      renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma,
      and glioblastoma express high levels of this antigen. To functionally target CD70
      expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to
      contain human IgG1 constant domains. The engineered antibody retained the binding
      specificity of the murine parent monoclonal antibody and was shown to induce Fc
      mediated effector functions including antibody-dependent cellular cytotoxicity,
      complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis
      in vitro. Further, administration of this antibody significantly prolonged
      survival of severe combined immunodeficient (SCID) mice bearing CD70+
      disseminated human NHL xenografts. Survival of these mice was dependent upon the
      activity of resident effector cells including neutrophils, macrophages, and
      natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when
      engineered to contain human IgG1 constant domains, possesses effector cell
      mediated antitumor activity and has potential utility for anticancer therapy.

PMID- 17038523
TI  - Mad2 is required for optimal hematopoiesis: Mad2 associates with c-Kit in MO7e
      cells.
AB  - Mitotic arrest deficiency 2 (Mad2) is a component of mitotic spindle checkpoint
      proteins and is essential for accurate chromosome segregation. We investigated a
      role for Mad2 in hematopoiesis using Mad2-haploinsufficient (Mad2+/-) mice.
      Mad2+/- bone marrow (BM) and spleen manifested decreased absolute numbers and
      cycling status of immature, but not mature, hematopoietic progenitor cells.
      Mad2+/- BM granulocyte-macrophage colony-forming units (CFU-GMs) did not manifest
      synergistic proliferation in response to stem cell factor (SCF) plus GM-CSF. The
      percentage of annexin V+ cells was higher in Mad2+/- than Mad2+/+c-Kit+lin- BM
      after culture with SCF and GM-CSF. However, no significant difference in
      phosphorylation of extracellular signal-related kinase (Erk1/2) at Thr202/Tyr204
      and Akt at Ser473 between Mad2+/- and Mad2+/+BM c-Kit+lin- cells was observed.
      Immunoprecipitation assays performed in human MO7e cells demonstrated physical
      association of c-Kit with Mad2. Moreover, stimulation with SCF plus GM-CSF led to
      dissociation of Mad2 from c-Kit. Confocal microscopy demonstrated that Mad2
      colocalized with c-Kit in the cytoplasm of MO7e cells. These results suggest that
      Mad2 is involved in synergistic growth of immature hematopoietic progenitor cells
      in response to SCF plus GM-CSF, effects that may be mediated via physical
      association of Mad2 with c-Kit.

PMID- 17038524
TI  - The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human
      B-cell lymphomas.
AB  - We previously developed a multivariate model based on the RNA expression of 6
      genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse
      large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest
      predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in
      order to study its tissue expression pattern. Immunohistologic analysis of over
      1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is
      expressed as a nuclear marker in normal germinal-center (GC) B cells and GC
      derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was
      also expressed in erythroid and myeloid precursors and in megakaryocytes and also
      in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature
      T, natural killer (NK), and plasma cell neoplasms and was absent from
      nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster
      analysis of immunohistologic data in DLBCL demonstrated that the expression
      profile of the LMO2 protein was similar to that of other GC-associated proteins
      (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and
      BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to
      construct a clinically applicable immunohistologic algorithm for predicting
      survival in patients with DLBCL.

PMID- 17038525
TI  - Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia.
AB  - Bone marrow transplantation (BMT) is the only known cure for the hematologic
      manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT
      for FA, however, have been severely limited by graft rejection and treatment
      related mortality with resultant poor survival. Therefore, we evaluated the
      impact of potential prognostic factors on hematopoietic recovery, graft-versus
      host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who
      received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs
      69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after
      fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of
      acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-cell
      depleted grafts. The day-100 mortality rate was significantly higher after
      nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs
      24%, respectively; P < .001). Corresponding 3-year adjusted overall survival
      rates were 13% versus 52% (P < .001). In addition, mortality was higher in
      recipients who were older (> 10 years), who were cytomegalovirus (CMV)
      seropositive, and who received more than 20 blood product transfusions before
      BMT. Based on these results, significant practice changes are suggested: use of a
      fludarabine-containing conditioning regimen in the context of T-cell-depleted
      marrow allografts, and earlier referral for transplantation prior to excessive
      transfusions in patients with marrow failure.

PMID- 17038526
TI  - Shear flow-dependent integration of apical and subendothelial chemokines in T
      cell transmigration: implications for locomotion and the multistep paradigm.
AB  - Lymphocyte extravasation requires that emigrating cells process chemoattractant
      signals, typically mediated by chemokines, encountered on endothelial surface
      (apical) and subendothelial (basal) compartments. These signals are delivered
      under conditions of hemodynamic shear, a fundamental feature of all physiologic
      leukocyte-endothelial interactions. To analyze lymphocyte responsiveness to
      spatially distributed chemokines and their effects on transendothelial migration
      (TEM) under hydrodynamic shear, we constructed a transwell-based flow assay. We
      observed that the inflammatory chemokine CCL5 (RANTES) induces negligible human T
      cell migration across inflamed human umbilical vascular endothelial cells
      (HUVECs) when displayed alone in the subendothelial compartment under static or
      hemodynamic shear conditions or when combined with apical CXCL12 (SDF-1alpha)
      under static conditions. However, under shear stress, T cells encountering
      apically presented CXCL12 were primed to undergo robust LFA-1-dependent TEM
      toward subendothelial CCL5. Notably, locomotive T cells arriving at endothelial
      junctions were retained and extended pseudopodia into and through the junctions,
      thereby increasing sensitivity to subendothelial CCL5. These findings provide the
      first evidence that lymphocytes integrate, conditional to shear forces,
      permissive apical chemokine deposits, and integrin engagement signals, resulting
      in morphologic changes and amplified chemotaxis to an otherwise weak
      subendothelial chemokine signal.

PMID- 17038527
TI  - The hypomorphic Gata1low mutation alters the proliferation/differentiation
      potential of the common megakaryocytic-erythroid progenitor.
AB  - Recent evidence suggests that mutations in the Gata1 gene may alter the
      proliferation/differentiation potential of hemopoietic progenitors. By single
      cell cloning and sequential replating experiments of prospectively isolated
      progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation
      increases the proliferation potential of a unique class of progenitor cells,
      similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs),
      but with the "unique" capacity to generate erythroblasts, megakaryocytes, and
      mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast
      cell progenitors (MCPs) are not detectable in the marrow from these mutants. At
      the single-cell level, about 11% of Gata1low progenitor cells, including MEPs,
      generate cells that will continue to proliferate in cultures for up to 4 months.
      In agreement with these results, trilineage (erythroid, megakaryocytic, and
      mastocytic) cell lines are consistently isolated from bone marrow and spleen
      cells of Gata1low mice. These results confirm the crucial role played by Gata1 in
      hematopoietic commitment and identify, as a new target for the Gata1 action, the
      restriction point at which common myeloid progenitors become either MEPs or MCPs.

PMID- 17038528
TI  - Contribution of Toll-like receptors to the innate immune response to Gram
      negative and Gram-positive bacteria.
AB  - Innate recognition of bacteria is a key step in the activation of inflammation
      and coagulation, and it is dependent on pathogen-associated molecular pattern
      (PAMP) ligation to Toll-like receptors (TLRs) and CD14. The dominant receptors
      activated when cells encounter a whole bacterium, which express several PAMPs,
      are poorly defined. Herein, we have stimulated various human cells with
      prototypic Gram-negative and Gram-positive bacteria. Receptor-dependent responses
      to whole bacteria were assessed using both TLR-transfected cells and specific
      monoclonal antibodies against TLRs, MD-2, and CD14. Enterobacteria-activated
      leukocytes and endothelial cells in a TLR4/MD-2-dependent manner, most likely via
      lipopolysaccharide (LPS). TLR2 activation was observed with a high bacterial
      inoculum, and in epithelial cells expressing TLR2 but not TLR4. Pseudomonas
      aeruginosa stimulated cells by both TLR2 and TLR4/MD-2. Gram-positive bacteria
      activated cells only at high concentrations, in a partially TLR2-dependent but
      TLR4/MD-2-independent manner. Either TLR or CD14 neutralization blocked
      activation to all bacterial strains tested with the exception of some Gram
      positive strains in whole blood in which partial inhibition was noted. This study
      identifies dominant TLRs involved in responses to whole bacteria. It also
      validates the concept that host cell activation by bacterial pathogens can be
      therapeutically reduced by anti-TLR4, -TLR2, and -CD14 mAbs.

PMID- 17038529
TI  - ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine
      kinase activation in chronic lymphocytic leukemia and lymphoma B cells.
AB  - Expression of ZAP-70 is an important negative prognostic factor in chronic
      lymphocytic leukemia (CLL). This protein tyrosine kinase is a key mediator of T
      cell receptor (TCR) signaling and is structurally homologous to Syk, which plays
      an analogous role in B-cell receptor (BCR) signaling. Recent studies indicate
      that ZAP-70 may participate in BCR signaling as well, but the mechanism of action
      is not completely understood. We have now compared antigen receptor-induced
      activation of ZAP-70 in B cells and T cells by analyzing phosphorylation of
      critical regulatory tyrosine residues. We show that BCR-mediated activation of
      ZAP-70 is very inefficient in CLL and lymphoma B cells and is negligible when
      compared to activation of Syk. Despite the inefficient catalytic activation, the
      ability of ZAP-70 to recruit downstream signaling molecules in response to
      antigen receptor stimulation appeared relatively preserved. Moreover, ectopic
      expression of ZAP-70 enhanced and prolonged activation of several key mediators
      of BCR signaling, such as the Syk, ERK, and Akt kinases, and decreased the rate
      of ligand-mediated BCR internalization. We conclude that the role of ZAP-70 in
      BCR signaling is quite distinct from its role in TCR signaling and is likely
      mediated by inhibition of events that terminate the signaling response.

PMID- 17038530
TI  - Toll-like receptors and their ligands control mesenchymal stem cell functions.
AB  - Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be
      involved in tissue maintenance and repair as well as in the regulation of
      hematopoiesis and immunologic responses. Thus, it is important to discover the
      factors controlling MSC renewal and differentiation. Here we report that adult
      MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of
      MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6
      secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation,
      reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC
      function is the capacity to differentiate into several mesodermal lineages. We
      show herein that Pam3Cys inhibited MSC differentiation into osteogenic,
      adipogenic, and chondrogenic cells while sparing their immunosuppressive effect.
      Our study therefore shows that a TLR ligand can antagonize MSC differentiation
      triggered by exogenous mediators and consequently maintains the cells in an
      undifferentiated and proliferating state in vitro. Moreover, MSCs derived from
      myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate
      effectively into osteogenic and chondrogenic cells. It appears that TLRs and
      their ligands can serve as regulators of MSC proliferation and differentiation
      and might affect the maintenance of MSC multipotency.

PMID- 17038531
TI  - Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and
      cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a
      two-event in vitro model.
AB  - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
      related mortality. Antibodies to HNA-3a are commonly implicated in TRALI. We
      hypothesized that HNA-3a antibodies prime neutrophils (PMNs) and cause PMN
      mediated cytotoxicity through a two-event pathogenesis. Isolated HNA-3a+ or HNA
      3a- PMNs were incubated with plasma containing HNA-3a antibodies implicated in
      TRALI, and their ability to prime the oxidase was measured. Human pulmonary
      microvascular endothelial cells (HMVECs) were activated with endotoxin or buffer,
      HNA-3a+ or HNA-3a- PMNs were added, and the coculture was incubated with plasma+/
      antibodies to HNA-3a. PMN-mediated damage was measured by counting viable
      HMVECs/mm2. Plasma containing HNA-3a antibodies primed the fMLP-activated
      respiratory burst of HNA-3a+, but not HNA-3a-, PMNs and elicited PMN-mediated
      damage of LPS-activated HMVECs when HNA-3a+, but not HNA-3a-, PMNs were used.
      Thus, antibodies to HNA-3a primed PMNs and caused PMN-mediated HMVEC cytotoxicity
      in a two-event model identical to biologic response modifiers implicated in
      TRALI.

PMID- 17038532
TI  - Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) increases
      vascular permeability: impaired permeability and angiogenesis in eNOS-deficient
      mice.
AB  - Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is emerging as an
      important regulator of vascular pathophysiology. Here, we demonstrate a novel
      role of RANKL as a vascular permeability factor and a critical role of
      endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function.
      RANKL increased the vascular permeability and leukocyte infiltration in vivo and
      caused the breakdown of the blood-retinal barrier in wild-type mice but not in
      eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced
      VE-cadherin-facilitated endothelial cell-cell junctions in a NO-dependent manner.
      RANKL also led to the activation of Akt and eNOS and to NO production in
      endothelial cells (ECs). These effects were suppressed by the inhibition of
      TRAF6, phosphoinositide 3'-kinase (PI3K), Akt, or NOS by genetic or pharmacologic
      means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and
      capillary-like tube formation in response to RANKL. Moreover, the effects of
      RANKL on ECs sprouting from the aorta, and neovessel formation in both the mouse
      Matrigel plug assay and corneal micropocket assay, were impaired in eNOS
      deficient mice. These results demonstrate that RANKL promotes vascular
      permeability and angiogenesis by stimulating eNOS by a TRAF6-PI3K-Akt-dependent
      mechanism. These properties may be relevant to the pathogenesis of angiogenesis
      dependent and inflammatory vascular diseases.

PMID- 17038533
TI  - Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens
      for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute
      myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).
AB  - To prospectively assess the applicability of reduced-intensity conditioning
      hematopoietic stem cell transplantation (RIC-HSCT), we wrote a protocol in which
      all untreated patients 50 years or older with acute myeloid leukemia (AML) and
      unfavorable cytogenetics would be evaluated during induction for a possible RIC
      HSCT in first complete remission (CR1). Ninety-nine of 259 patients entered CR.
      Fifty-three of the 99 were seen by the Transplant Service with the remainder not
      seen because of illness, lack/unavailability of siblings, refusal, or, primarily,
      unclear reasons (21 patients). A donor was identified for 26 patients (21
      sibling, 5 unrelated) with RIC-HSCT performed in 14 (13 sibling). Results in
      consulted patients suggested that 50% or fewer of the 85 patients who did not
      undergo transplantation were potential transplant candidates. We attempted to
      find one or more chemotherapy pair-mates for each patient who underwent
      transplantation based on cytogenetics, age, and a relapse-free survival (RFS)
      time that was more than or equal to the time from CR1 to RIC-HSCT in the patient
      who underwent transplantation. Thirty-two of the 39 matches favored (longer RFS)
      RIC-HSCT and 7, chemotherapy. The probability that the corresponding beta
      distribution was different than expected (ie, that RIC-HSCT was superior) was
      0.99 (P=.004). Results were similar with respect to survival. While RIC-HSCT thus
      seems of interest, methods are needed to extend its applicability.

PMID- 17038534
TI  - Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic
      lymphocytic leukemia cells correlates with survival capacity.
AB  - The gradual accumulation of chronic lymphocytic leukemia (B-CLL) cells is
      presumed to derive from proliferation centers in lymph nodes and bone marrow. To
      what extent these cells possess the purported antiapoptotic phenotype of
      peripheral B-CLL cells is unknown. Recently, we have described that, in B-CLL
      samples from peripheral blood, aberrant apoptosis gene expression was not limited
      to protective changes but also included increased levels of proapoptotic BH3-only
      member Noxa. Here, we compare apoptosis gene profiles from peripheral blood B-CLL
      (n=15) with lymph node B-CLL (>90% CD5+/CD19+/CD23+ lymphocytes with Ki67+
      centers; n=9). Apart from expected differences in Survivin and Bcl-xL, a
      prominent distinction with peripheral B-CLL cells was the decreased averaged
      level of Noxa in lymph nodes. Mcl-1 protein expression showed a reverse trend.
      Noxa expression could be reduced also in vitro by CD40 stimulation of peripheral
      blood B-CLL. Direct manipulation of Noxa protein levels was achieved by
      proteasome inhibition in B-CLL and via RNAi in model cell lines. In each
      instance, cell viability was directly linked with Noxa levels. These data
      indicate that suppression of Noxa in the lymph node environment contributes to
      the persistence of B-CLL at these sites and suggest that therapeutic targeting of
      Noxa might be beneficial.

PMID- 17038535
TI  - Production of interferons by dendritic cells, plasmacytoid cells, natural killer
      cells, and interferon-producing killer dendritic cells.
AB  - The capacity of mouse spleen conventional dendritic cells (cDCs) and plasmacytoid
      dendritic cells (pDCs) to produce interferon-gamma (IFN-gamma) or IFN-alpha was
      assessed, and compared with that of natural killer (NK) cells and the recently
      identified interferon-producing killer dendritic cells (IKDCs), both of which are
      frequent contaminants in DC preparations. Fully developed cDCs or pDCs, if free
      of NK cells or IKDCs, showed little capacity for IFN-gamma production. However,
      an early developmental form of the CD4-8+ cDC subtype, and the Ly6C- Ly49Q- pDC
      subtype, both were able to produce moderate amounts of IFN-gamma, although less
      than IKDCs. In response to toll-like receptor 9 stimuli, both the Ly6C+ Ly49Q+
      and the Ly6C- Ly49Q- pDC subtypes were effective producers of IFN-alpha. However,
      IKDCs, which efficiently produced IFN-gamma and showed immediate cytotoxicity on
      NK target cells, did not produce IFN-alpha under these conditions.

PMID- 17038536
TI  - Comparative single-institute analysis of cord blood transplantation from
      unrelated donors with bone marrow or peripheral blood stem-cell transplants from
      related donors in adult patients with hematologic malignancies after
      myeloablative conditioning regimen.
AB  - We studied the clinical outcomes of 171 adults with hematologic malignancies who
      received unrelated cord blood transplantation (CBT) as a primary unrelated stem
      cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem
      cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All
      patients received myeloablative regimens including 12 Gy total body irradiation.
      We analyzed the hematologic recovery, and risks of graft-versus-host disease
      (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free
      survival (DFS) using Cox proportional hazards models. Significant delays in
      engraftment occurred after cord blood transplantation; however, overall
      engraftment rates were almost the same for both grafts. The cumulative incidences
      of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients
      were significantly lower than those among BMT/PBSCT recipients. Multivariate
      analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in
      BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and
      DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data
      suggest that unrelated cord blood could be as safe and effective a stem-cell
      source as related bone marrow or mobilized peripheral blood for adult patients
      when it is used as a primary unrelated stem-cell source.

PMID- 17038537
TI  - Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and
      activation of this pathway is defective in HIV patients.
AB  - An important mechanism of host defense to Cryptococcus neoformans involves the
      direct microbicidal activity of lymphocytes. The importance of CD4+ T cells is
      illustrated by the incidence of this infection in the acquired immunodeficiency
      syndrome (AIDS) patients; however, the relative activity of microbicidal CD4+ T
      cells compared with CD8+ T cells and natural killer (NK) cells has not been
      established. Further, although NK cells and CD8+ T cells use perforin or
      granulysin, respectively, to kill C neoformans, the effector molecule used by
      CD4+ T cells is not known. Experiments demonstrated that IL-2-activated
      peripheral blood lymphocytes from healthy adults acquire anticryptococcal
      activity, and surprisingly, that CD4+ T cells had the most profound effect on
      this activity. Using SrCl(2)induced degranulation and siRNA knockdown, granulysin
      was shown to be the effector molecule. Although activation by anti-CD3 + IL-2
      resulted in the additional expression of perforin, this did not improve the
      anticryptococcal activity. Cryptococcal killing by CD4+ T cells was defective in
      human immunodeficiency virus (HIV)-infected patients due to dysregulated
      granulysin and perforin production in response to IL-2 or anti-CD3 + IL-2. In
      conclusion, CD4+ T cells are the major subset of cells responsible for killing C
      neoformans in peripheral blood. These cells use granulysin as the effector
      molecule, and priming is dysregulated in HIV-infected patients, which results in
      defective microbicidal activity.

PMID- 17038538
TI  - Dissecting the role of endothelial SURVIVIN DeltaEx3 in angiogenesis.
AB  - The identification of alternative splice variants of Survivin that possess
      distinct functions from those originally identified for the main Survivin isoform
      has greatly increased the complexity of our understanding of the role of Survivin
      in different cells. Previous functional studies of the Survivin splice variants
      have been performed almost exclusively in cancer cells. However, Survivin has
      increasingly been implicated in other normal physiologic and pathophysiologic
      processes, including angiogenesis. In this study, we dissect the involvement of
      Survivin DeltaEx3 in angiogenesis. We show by confocal microscopy that a pool of
      endothelial Survivin DeltaEx3 is localized to membrane ruffles. We also
      demonstrate that Survivin DeltaEx3 is the Survivin splice variant responsible for
      modulating angiogenesis in vitro, in tube formation assays, and in vivo, in an in
      vivo angiogenesis assay. Our data indicate that Survivin DeltaEx3 may regulate
      angiogenesis via several mechanisms including cell invasion, migration, and Rac1
      activation. Our findings identify a novel pathway regulating angiogenesis through
      Survivin DeltaEx3 and a novel mechanism for Rac1 activation during angiogenesis.
      In conclusion, our results provide new insights into the regulation of
      endothelial cell homeostasis and angiogenesis by the Survivin proteins.

PMID- 17038539
TI  - Constitutive activation of Stat5 promotes its cytoplasmic localization and
      association with PI3-kinase in myeloid leukemias.
AB  - Persistent activation of Stat5 is frequently found in hematologic neoplasms.
      Studies conducted with constitutively active Stat5 mutants (Stat51*6 and cS5F)
      have shown that deregulated Stat5 activity promotes leukemogenesis. To
      investigate the oncogenic properties of these mutants, we used cS5F-expressing
      bone marrow cells which induce a multilineage leukemia when transplanted into
      recipient mice. Here, we show by immunocytochemistry that cS5F is localized
      mainly in the cytoplasmic compartment of leukemic cells, suggesting that the
      transforming nature of cS5F may be associated with a cytoplasmic function. In
      support of this hypothesis, we found that cS5F forms a complex with the p85
      subunit of the phosphatidylinositol 3-kinase (PI3-K) and the scaffolding adapter
      Gab2 in leukemic bone marrow cells, resulting in the activation of Akt/PKB, a
      crucial downstream target of PI3-K. By using transducible TAT-Gab2 or TAT-Akt
      recombinant proteins, we were able to demonstrate that activation of the PI3
      kinase/Akt pathway by cS5F molecules through Gab2 is essential for induction of
      cell growth. We also found that persistently phosphorylated Stat5 in primary
      cells from patients with myeloid leukemias has a cytoplasmic localization. These
      data suggest that oncogenic Stat5 proteins exert dual transforming capabilities
      not only as transcriptional activators but also as cytoplasmic signaling
      effectors.

PMID- 17038540
TI  - The spindle checkpoint.

PMID- 17038541
TI  - Microtubule nucleation: gamma-tubulin and beyond.
AB  - Centrosomes and their fungal equivalents, spindle pole bodies (SPBs), are the
      main microtubule (MT)-organizing centers in eukaryotic cells. Several proteins
      have been implicated in microtubule formation by centrosomes and SPBs, including
      microtubule-minus-end-binding proteins and proteins that bind along the length or
      stabilize the plus ends of microtubules. Recent work has improved our
      understanding of the molecular mechanisms of MT formation. In particular, it has
      shown that gamma-tubulin and its associated proteins play key roles in
      microtubule nucleation and spindle assembly in evolutionarily distant species
      ranging from fungi to mammals. Other work indicates that gamma-tubulin-mediated
      microtubule nucleation, although necessary, is not sufficient for mitotic spindle
      assembly but requires additional proteins that regulate microtubule nucleation
      independently of centrosomes.

PMID- 17038542
TI  - Generation of noncentrosomal microtubule arrays.
AB  - In most proliferating and migrating animal cells, the centrosome is the main site
      for microtubule (MT) nucleation and anchoring, leading to the formation of radial
      MT arrays in which MT minus ends are anchored at the centrosomes and plus ends
      extend to the cell periphery. By contrast, in most differentiated animal cell
      types, including muscle, epithelial and neuronal cells, as well as most fungi and
      vascular plant cells, MTs are arranged in noncentrosomal arrays that are non
      radial. Recent studies suggest that these noncentrosomal MT arrays are generated
      by a three step process. The initial step involves formation of noncentrosomal
      MTs by distinct mechanisms depending on cell type: release from the centrosome,
      catalyzed nucleation at noncentrosomal sites or breakage of pre-existing MTs. The
      second step involves transport by MT motor proteins or treadmilling to sites of
      assembly. In the final step, the noncentrosomal MTs are rearranged into cell-type
      specific arrays by bundling and/or capture at cortical sites, during which MTs
      acquire stability. Despite their relative stability, the final noncentrosomal MT
      arrays may still exhibit dynamic properties and in many cases can be remodeled.

PMID- 17038543
TI  - The synapsin domain E accelerates the exoendocytotic cycle of synaptic vesicles
      in cerebellar Purkinje cells.
AB  - Synapsins are synaptic-vesicle-associated phosphoproteins implicated in the
      regulation of neurotransmitter release and excitability of neuronal networks.
      Mutation of synapsin genes in mouse and human causes epilepsy. To understand the
      role of the highly conserved synapsin domain E in the dynamics of release from
      mammalian inhibitory neurons, we generated mice that selectively overexpress the
      most conserved part of this domain in cerebellar Purkinje cells. At Purkinje-cell
      nuclear-neuron synapses, transgenic mice were more resistant to depression
      induced by short or prolonged high-frequency stimulations. The increased synaptic
      performance was accompanied by accelerated release kinetics and shorter synaptic
      delay. Despite a marked decrease in the total number of synaptic vesicles,
      vesicles at the active zone were preserved or slightly increased. The data
      indicate that synapsin domain E increases synaptic efficiency by accelerating
      both the kinetics of exocytosis and the rate of synaptic vesicle cycling and
      decreasing depression at the inhibitory Purkinje-cell-nuclear-neuron synapse.
      These effects may increase the sensitivity of postsynaptic neurons to inhibition
      and thereby contribute to the inhibitory control of network activity.

PMID- 17038544
TI  - Increased Rheb-TOR signaling enhances sensitivity of the whole organism to
      oxidative stress.
AB  - The accumulation of free radical damage to an organism over its lifespan can
      cause premature aging and disease including cancer, atherosclerosis and
      neurodegenerative disorders. The well-conserved Rheb-Target-of-rapamycin (TOR)-S6
      kinase (S6K) signaling pathway regulates several cellular processes and has been
      shown to influence lifespan and diseases such as cancer and neurodegenerative
      disorders. Using adult Drosophila, we describe for the first time in metazoans
      that TOR activity can influence the stress response. We find that mildly
      increasing systemic Rheb-TOR-S6K signaling sensitizes the whole organism to
      oxidative stress and promotes senescence of locomotor activity with age.
      Furthermore, we find that S6K is required for increased Rheb-TOR signaling to
      sensitize the whole organism to oxidative stress and promote the senescence of
      locomotor activity. Interestingly, we also find that increasing Rheb-TOR
      signaling in muscle can increase the sensitivity of adults to oxidative stress.
      These data imply that pathological situations that increase TOR activity might
      perturb the ability of the whole organism to cope with stress causing disease
      progression and aging.

PMID- 17038545
TI  - HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage.
AB  - Class II histone deacetylases (HDAC4, HDAC5, HDAC7 and HDAC9) have been shown to
      interact with myocyte enhancer factors 2 (MEF2s) and play an important role in
      the repression of cardiac hypertrophy. We examined the role of HDACs during the
      differentiation of P19 embryonic carcinoma stem cells into cardiomyocytes.
      Treatment of aggregated P19 cells with the HDAC inhibitor trichostatin A induced
      the entry of mesodermal cells into the cardiac muscle lineage, shown by the
      upregulation of transcripts Nkx2-5, MEF2C, GATA4 and cardiac alpha-actin.
      Furthermore, the overexpression of HDAC4 inhibited cardiomyogenesis, shown by the
      downregulation of cardiac muscle gene expression. Class II HDAC activity is
      inhibited through phosphorylation by Ca2+/calmodulin-dependent kinase (CaMK).
      Expression of an activated CaMKIV in P19 cells upregulated the expression of Nkx2
      5, GATA4 and MEF2C, enhanced cardiac muscle development, and activated a MEF2
      responsive promoter. Moreover, inhibition of CaMK signaling downregulated GATA4
      expression. Finally, P19 cells constitutively expressing a dominant-negative form
      of MEF2C, capable of binding class II HDACs, underwent cardiomyogenesis more
      efficiently than control cells, implying the relief of an inhibitor. Our results
      suggest that HDAC activity regulates the specification of mesoderm cells into
      cardiomyoblasts by inhibiting the expression of GATA4 and Nkx2-5 in a stem cell
      model system.

PMID- 17038546
TI  - Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere
      formation.
AB  - Titin, a multifunctional protein that stretches from the Z-disk to the M-band in
      heart and skeletal muscle, contains a kinase domain, phosphorylation sites and
      multiple binding sites for structural and signalling proteins in the M-band. To
      determine whether this region is crucial for normal sarcomere development, we
      created mouse embryonic stem cell (ES) lines in which either one or both alleles
      contained a targeted deletion of the entire M-band-coding region, leaving Z-disk
      binding and myosin-filament-binding sites intact. ES cells were differentiated
      into cardiomyocytes, and myofibrillogenesis investigated by immunofluorescence
      microscopy. Surprisingly, deletion of one allele did not markedly affect
      differentiation into cardiomyocytes, suggesting that a single intact copy of the
      titin gene is sufficient for normal myofibrillogenesis. By contrast, deletion of
      both alleles resulted in a failure of differentiation beyond an early stage of
      myofibrillogenesis. Sarcomeric myosin remained in non-striated structures, Z-disk
      proteins, such as alpha-actinin, were mainly found in primitive dot-like
      structures on actin stress fibres, M-band-associated proteins (myomesin,
      obscurin, Nbr1, p62 and MURF2) remained punctate. These results show that
      integration of the M-band region of titin is required for myosin filament
      assembly, M-band formation and maturation of the Z-disk.

PMID- 17038547
TI  - A role for non-muscle myosin II function in furrow maturation in the early
      zebrafish embryo.
AB  - Cytokinesis in early zebrafish embryos involves coordinated changes in the f
      actin- and microtubule-based cytoskeleton, and the recruitment of adhesion
      junction components to the furrow. We show that exposure to inhibitors of non
      muscle myosin II function does not affect furrow ingression during the early
      cleavage cycles but interferes with the recruitment of pericleavage f-actin and
      cortical beta-catenin aggregates to the furrow, as well as the remodeling of the
      furrow microtubule array. This remodeling is in turn required for the distal
      aggregation of the zebrafish germ plasm. Embryos with reduced myosin activity
      also exhibit at late stages of cytokinesis a stabilized contractile ring
      apparatus that appears as a ladder-like pattern of short f-actin cables,
      supporting a role for myosin function in the disassembly of the contractile ring
      after furrow formation. Our studies support a role for myosin function in furrow
      maturation that is independent of furrow ingression and which is essential for
      the recruitment of furrow components and the remodeling of the cytoskeleton
      during cytokinesis.

PMID- 17038549
TI  - Isolated autosomal dominant growth hormone deficiency: stimulating mutant GH-1
      gene expression drives GH-1 splice-site selection, cell proliferation, and
      apoptosis.
AB  - The majority of mutations that cause isolated GH deficiency type II (IGHD II)
      affect splicing of GH-1 transcripts and produce a dominant-negative GH isoform
      lacking exon 3 resulting in a 17.5-kDa isoform, which further leads to disruption
      of the GH secretory pathway. A clinical variability in the severity of the IGHD
      II phenotype depending on the GH-1 gene alteration has been reported, and in
      vitro and transgenic animal data suggest that the onset and severity of the
      phenotype relates to the proportion of 17.5-kDa produced. The removal of GH in
      IGHD creates a positive feedback loop driving more GH expression, which may
      itself increase 17.5-kDa isoform productions from alternate splice sites in the
      mutated GH-1 allele. In this study, we aimed to test this idea by comparing the
      impact of stimulated expression by glucocorticoids on the production of different
      GH isoforms from wild-type (wt) and mutant GH-1 genes, relying on the
      glucocorticoid regulatory element within intron 1 in the GH-1 gene. AtT-20 cells
      were transfected with wt-GH or mutated GH-1 variants (5'IVS-3 + 2-bp T->C; 5'IVS
      3 + 6 bp T->C; ISEm1: IVS-3 + 28 G->A) known to cause clinical IGHD II of varying
      severity. Cells were stimulated with 1 and 10 mum dexamethasone (DEX) for 24 h,
      after which the relative amounts of GH-1 splice variants were determined by
      semiquantitative and quantitative (TaqMan) RT-PCR. In the absence of DEX, only
      around 1% wt-GH-1 transcripts were the 17.5-kDa isoform, whereas the three mutant
      GH-1 variants produced 29, 39, and 78% of the 17.5-kDa isoform. DEX stimulated
      total GH-1 gene transcription from all constructs. Notably, however, DEX
      increased the amount of 17.5-kDa GH isoform relative to the 22- and 20-kDa
      isoforms produced from the mutated GH-1 variants, but not from wt-GH-1. This DEX
      induced enhancement of 17.5-kDa GH isoform production, up to 100% in the most
      severe case, was completely blocked by the addition of RU486. In other studies,
      we measured cell proliferation rates, annexin V staining, and DNA fragmentation
      in cells transfected with the same GH-1 constructs. The results showed that that
      the 5'IVS-3 + 2-bp GH-1 gene mutation had a more severe impact on those measures
      than the splice site mutations within 5'IVS-3 + 6 bp or ISE +28, in line with the
      clinical severity observed with these mutations. Our findings that the proportion
      of 17.5-kDa produced from mutant GH-1 alleles increases with increased drive for
      gene expression may help to explain the variable onset progression, and severity
      observed in IGHD II.

PMID- 17038548
TI  - Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface
      transport of ATP-sensitive K+ channels.
AB  - Arginine (Arg)-based endoplasmic reticulum (ER)-localization signals are involved
      in the quality control of different heteromultimeric membrane protein complexes.
      ATP-sensitive potassium (KATP) channels are unique because each subunit in the
      heterooctamer contains an Arg-based ER-localization signal. We have dissected the
      inactivation events that override the ER-localization activity of the eight
      peptide-sorting motifs. Employing a 14-3-3-scavenger construct to lower the
      availability of 14-3-3 proteins, we found that 14-3-3 proteins promote the cell
      surface expression of heterologously expressed and native KATP channels. 14-3-3
      proteins were detected in physical association with KATP channels in a pancreatic
      beta-cell line. Our results suggest that the Arg-based signal present in Kir6.2
      is sterically masked by the SUR1 subunit. By contrast, 14-3-3 proteins
      functionally antagonized the Arg-based signal present in SUR1. The last ten amino
      acids were required for efficient 14-3-3 recruitment to multimeric forms of the
      Kir6.2 C-terminus. Channels containing a pore-forming subunit lacking these
      residues reached the cell surface inefficiently but were functionally
      indistinguishable from channels formed by the full-length subunits. In
      conclusion, 14-3-3 proteins promote the cell-surface transport of correctly
      assembled complexes but do not regulate the activity of KATP channels at the cell
      surface.

PMID- 17038550
TI  - Arsenite modulates cardiac substrate preference by translocation of GLUT4, but
      not CD36, independent of mitogen-activated protein kinase signaling.
AB  - The protein thiol-modifying agent arsenite, a potent activator of stress
      signaling, was used to examine the involvement of MAPKs in the regulation of
      cardiac substrate uptake. Arsenite strongly induced p38 MAPK phosphorylation in
      isolated rat cardiac myocytes but also moderately enhanced phosphorylation of
      p42/44 ERK and p70 S6K. At the level of cardiomyocytic substrate use, arsenite
      enhanced glucose uptake dose dependently up to 5.1-fold but failed to stimulate
      long-chain fatty acid uptake. At the substrate transporter level, arsenite
      stimulated the translocation of GLUT4 to the sarcolemma but failed to recruit
      CD36 or FABPpm. Because arsenite did not influence the intrinsic activity of
      glucose transporters, GLUT4 translocation is entirely responsible for the
      selective increase in glucose uptake by arsenite. Moreover, the nonadditivity of
      arsenite-induced glucose uptake and insulin-induced glucose uptake indicates that
      arsenite recruits GLUT4 from insulin-responsive intracellular stores. Inhibitor
      studies with SB203580/SB202190, PD98059, and rapamycin indicate that activation
      of p38 MAPK, p42/44 ERK, and p70 S6K, respectively, are not involved in arsenite
      induced glucose uptake. In addition, all these kinases do not play a role in
      regulation of cardiac glucose and long-chain fatty acid uptake by insulin. Hence,
      arsenite's selective stimulation of glucose uptake appears unrelated to its
      signaling actions, suggesting that arsenite acts via thiol modification of a
      putative intracellular protein target of arsenite within insulin-responsive GLUT4
      containing stores. Because of arsenite's selective stimulation of cardiac glucose
      uptake, identification of this putative target of arsenite within the GLUT4
      storage compartment may indicate whether it is a target for future strategies in
      prevention of diabetic cardiomyopathy.

PMID- 17038552
TI  - Regulation of pituitary cell function by adiponectin.
AB  - Adiponectin is a member of the family of adipose tissue-related hormones known as
      adipokines, which exerts antidiabetic, antiatherogenic, antiinflammatory, and
      antiangiogenic properties. Adiponectin actions are primarily mediated through
      binding to two receptors expressed in several tissues, AdipoR1 and AdipoR2.
      Likewise, adiponectin expression has been detected in adipocytes as well as in a
      variety of extra-adipose tissues, including the chicken pituitary. Interestingly,
      adiponectin secretion and adiponectin receptor expression in adipocytes have been
      shown to be regulated by pituitary hormones. These observations led us to
      investigate whether adiponectin, like the adipokine leptin, regulates pituitary
      hormone production. Specifically, we focused our analysis on somatotrophs and
      gonadotrophs because of the relationship between the control of energy
      metabolism, growth and reproduction. To this end, the effects of adiponectin on
      both GH and LH secretion as well as its interaction with major stimulatory
      regulators of somatotrophs (ghrelin and GHRH) and gonadotrophs (GnRH) and with
      their corresponding receptors (GHS-R, GHRH-R, and GnRH-R), were evaluated in rat
      pituitary cell cultures. Results show that adiponectin inhibits GH and LH release
      as well as both ghrelin-induced GH release and GnRH-stimulated LH secretion in
      short-term (4 h) treated cell cultures, wherein the adipokine also increases GHRH
      R and GHS-R mRNA content while decreasing that of GnRH-R. Additionally, we
      demonstrate that the pituitary expresses both adiponectin and adiponectin
      receptors under the regulation of the adipokine. In sum, our data indicate that
      adiponectin, either locally produced or from other sources, may play a
      neuroendocrine role in the control of both somatotrophs and gonadotrophs.

PMID- 17038551
TI  - Estrogen decrease in tight junctional resistance involves matrix
      metalloproteinase-7-mediated remodeling of occludin.
AB  - Estrogen modulates tight junctional resistance through estrogen receptor-alpha
      mediated remodeling of occludin. The objective of the study was to understand the
      mechanisms involved. Experiments using human normal vaginal-cervical epithelial
      cells showed that human normal vaginal-cervical epithelial cells secrete
      constitutively matrix-metalloproteinase-7 (MMP-7) into the luminal solution and
      that MMP-7 is necessary and sufficient to produce estrogen decrease of tight
      junctional resistance and remodeling of occludin. Treatment with estrogen
      stimulated activation of the pro-MMP-7 intracellularly and augmented secretion of
      the activated MMP-7 form. Steady-state levels of MMP-7 mRNA and protein were not
      affected by estrogen. Estrogen modulated phosphorylation of the MMP-7, but the
      changes were most likely secondary to changes in cellular MMP-7 mass. Estrogen
      increased coimmunoreactivity of MMP-7 with the Golgi protein GPP130. Tunicamycin
      and brefeldin-A had no effect on cellular MMP-7 but monensin (inhibitor of Golgi
      traffic) blocked estrogen effects, suggesting estrogen site of action is at the
      Golgi system. Estrogen increased generalized secretory activity, including of
      luminal exocytosis of polycarbohydrates. However, estrogen increased
      coimmunoreactivity of MMP-7 with synaptosomal-associated protein of 25 kDa in
      apical membranes, suggesting soluble N-ethylmaleimide sensitive fusion factor
      attachment protein receptor-facilitated exocytosis of MMP-7. Treatment with the
      vesicular-ATPase inhibitor bafilomycin A(1) inhibited activation of MMP-7. These
      data suggest that estrogen up-regulates activation of the MMP-7 intracellularly,
      at the level of Golgi, and augments secretion of activated MMP-7 through soluble
      N-ethylmaleimide sensitive fusion factor attachment protein receptor-dependent
      exocytosis. On the other hand, estrogen acidification of the luminal solution
      would tend to alkalinize exocytotic vesicles and may lead to decreased activation
      of the MMP-7. These mechanisms acting in concert could be important for
      regulation and control of estrogen modulation of paracellular permeability in
      vivo.

PMID- 17038553
TI  - The inhibitory effect of leptin on angiotensin II-induced vasoconstriction in
      vascular smooth muscle cells is mediated via a nitric oxide-dependent mechanism.
AB  - Leptin inhibits the contractile response induced by angiotensin (Ang) II in
      vascular smooth muscle cells (VSMCs) of the aorta. We studied in vitro and ex
      vivo the role of nitric oxide (NO) in the effect of leptin on the Ang II-induced
      vasoconstriction of the aorta of 10-wk-old Wistar rats. NO and nitric oxide
      synthase (NOS) activity were assessed by the Griess and (3)H-arginine/citrulline
      conversion assays, respectively. Stimulation of inducible NOS (iNOS) as well as
      Janus kinases/signal transducers and activators of transcription (JAK/STAT) and
      phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were determined by
      Western blot. The contractile responses to Ang II were evaluated in endothelium
      denuded aortic rings using the organ bath system. Changes in intracellular Ca(2+)
      were measured in VSMCs using fura-2 fluorescence. Leptin significantly (P < or =
      0.01) stimulated NO release and NOS activity in VSMCs. Leptin's effect on NO was
      abolished by the NOS inhibitor, N(G)-monomethyl l-arginine, or the iNOS selective
      inhibitor L-N(6)-(1-iminoethyl)-lysine. Accordingly, leptin increased iNOS
      protein expression, with a comparable time course with that of NO production and
      NOS activity. Leptin also significantly increased STAT3 (P < or = 0.01) and Akt
      (P < or = 0.001) phosphorylation. Moreover, either the JAK2 inhibitor, AG490, or
      the PI3K inhibitor, wortmannin, significantly (P < or = 0.05) abrogated the
      leptin-induced increase in iNOS protein. Finally, both N(G)-monomethyl L-arginine
      and L-N(6)-(1-iminoethyl)-lysine inhibitors completely blunted (P < or = 0.001)
      the leptin-mediated inhibition of the Ang II-induced VSMC activation and
      vasoconstriction. These findings suggest that the endothelium-independent
      depressor action of leptin is mediated by an increase of NO bioavailability in
      VSMCs. This process requires the up-regulation of iNOS through mechanisms
      involving JAK2/STAT3 and PI3K/Akt pathways.

PMID- 17038554
TI  - A novel mutation in the bone morphogenetic protein 15 gene causing defective
      protein secretion is associated with both increased ovulation rate and sterility
      in Lacaune sheep.
AB  - Genetic mutations with major effects on ovulation rate and litter size in sheep
      were recently identified in three genes belonging to the TGFbeta superfamily
      pathway: the bone morphogenetic protein 15 (BMP15, also known as GDF9b), growth
      differentiation factor 9 (GDF9), and BMP receptor type IB (also known as activin
      like kinase 6). Homozygous BMP15 or GDF9 mutations raise female sterility due to
      a failure of normal ovarian follicle development, whereas heterozygous animals
      for BMP15 or GDF9 as well as heterozygous and homozygous animals for BMP receptor
      type IB show increased ovulation rates. In the present work, a new naturally
      occurring mutation in the BMP15 gene in the high prolific Lacaune sheep breed is
      described. The identified variant is a C53Y missense nonconservative substitution
      leading to the aminoacidic change of a cysteine with a tyrosine in the mature
      peptide of the protein. As for other mutations found in the same gene, this is
      associated with an increased ovulation rate and sterility in heterozygous and
      homozygous animals, respectively. Further in vitro studies showed that the C53Y
      mutation was responsible for the impairment of the maturation process of the
      BMP15 protein, resulting in a defective secretion of both the precursor and
      mature peptide. Overall, our findings confirm the essential role of the BMP15
      factor in the ovarian folliculogenesis and control of ovulation rate in sheep.

PMID- 17038555
TI  - Tumor necrosis factor-alpha regulates steroidogenesis, apoptosis, and cell
      viability in the human adrenocortical cell line NCI-H295R.
AB  - TNF-alpha regulates the hypothalamo-pituitary-adrenal axis at several levels. It
      has been shown to modify adrenal steroidogenesis in many species, and it is
      supposed to act as an auto/paracrine factor. However, its significance in human
      adrenocortical function remains unclear. Therefore, we investigated the effect of
      TNF-alpha on adrenal steroidogenesis, expression of the key steroidogenic genes,
      apoptosis, and cell viability in the human adrenocortical cell line NCI-H295R.
      TNF-alpha treatment (1 nM for 48 h) decreased the basal production of cortisol,
      androstenedione, dehydroepiandrosterone sulfate (DHEAS), and aldosterone (14, 18,
      35, and 52%, respectively), and the 8-bromo-cAMP-induced production of cortisol,
      androstenedione, dehydroepiandrosterone (DHEA), and DHEAS (44, 66, 58, and 48%,
      respectively). However, when the steroid production data were normalized by the
      cell number, TNF-alpha increased the basal production of cortisol,
      androstenedione, DHEA, DHEAS, and aldosterone (137, 121, 165, 73, and 28%,
      respectively), and the 8-bromo-cAMP-induced production of cortisol, DHEAS, and
      aldosterone (122, 121, and 256%, respectively). This was accompanied by a
      parallel increase in the expression of the genes encoding for the steroidogenic
      acute regulatory protein, 3beta-hydroxysteroid dehydrogenase 2, and 17
      hydroxylase/17,20-lyase (74, 200, and 50%, respectively; quantitative real-time
      RT-PCR analysis). TNF-alpha increased caspase 3/7 activity (an indicator of
      apoptosis) and decreased cell viability dose and time dependently. The effect of
      TNF-alpha on apoptosis was neutralized by a monoclonal TNF-alpha antibody. These
      findings indicate that TNF-alpha is a potent regulator of steroidogenesis and
      cell viability in adrenocortical cells. TNF-alpha may have physiological and/or
      pathophysiological significance as an endocrine and/or paracrine/autocrine
      regulator of adrenocortical function.

PMID- 17038556
TI  - Interleukin-1beta-induced insulin resistance in adipocytes through down
      regulation of insulin receptor substrate-1 expression.
AB  - Inflammation is associated with obesity and insulin resistance. Proinflammatory
      cytokines produced by adipose tissue in obesity could alter insulin signaling and
      action. Recent studies have shown a relationship between IL-1beta level and
      metabolic syndrome or type 2 diabetes. However, the ability of IL-1beta to alter
      insulin signaling and action remains to be explored. We demonstrated that IL
      1beta slightly increased Glut 1 translocation and basal glucose uptake in 3T3-L1
      adipocytes. Importantly, we found that prolonged IL-1beta treatment reduced the
      insulin-induced glucose uptake, whereas an acute treatment had no effect. Chronic
      treatment with IL-1beta slightly decreased the expression of Glut 4 and markedly
      inhibited its translocation to the plasma membrane in response to insulin. This
      inhibitory effect was due to a decrease in the amount of insulin receptor
      substrate (IRS)-1 but not IRS-2 expression in both 3T3-L1 and human adipocytes.
      The decrease in IRS-1 amount resulted in a reduction in its tyrosine
      phosphorylation and the alteration of insulin-induced protein kinase B activation
      and AS160 phosphorylation. Pharmacological inhibition of ERK totally inhibited IL
      1beta-induced down-regulation of IRS-1 mRNA. Moreover, IRS-1 protein expression
      and insulin-induced protein kinase B activation, AS160 phosphorylation, and Glut
      4 translocation were partially recovered after treatment with the ERK inhibitor.
      These results demonstrate that IL-1beta reduces IRS-1 expression at a
      transcriptional level through a mechanism that is ERK dependent and at a
      posttranscriptional level independently of ERK activation. By targeting IRS-1, IL
      1beta is capable of impairing insulin signaling and action, and could thus
      participate in concert with other cytokines, in the development of insulin
      resistance in adipocytes.

PMID- 17038557
TI  - Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin
      resistance with age.
AB  - Animals at advanced ages exhibit a reduction in central leptin sensitivity.
      However, changes in growth, metabolism, and obesity risk occur much earlier in
      life, particularly during the transition from youth to middle age. To determine
      when initial decreases in central leptin sensitivity occur, leptin-dependent
      suppression of food intake was tested in 8-, 12-, and 20-wk-old male, chow-fed
      Sprague Dawley rats. Intracerebroventricular leptin injection (3 microg)
      suppressed 24-h food intake in 8- and 12-wk-old rats (P < 0.05) but not 20-wk-old
      rats. To identify potential cellular mediators of this resistance, we focused on
      protein tyrosine phosphatase 1B (PTP1B), a recently described inhibitor of leptin
      signaling. PTP1B protein levels, as determined by Western blot, were
      significantly higher in mediobasal hypothalamic punches collected from 20-wk-old
      rats, compared with 8-wk-old rats (P < 0.05). When 20-wk-old rats were fasted for
      24 h, levels of hypothalamic PTP1B decreased (P < 0.05), coincident with a
      restoration of leptin sensitivity. To directly test whether inhibition of PTP1B
      restores leptin sensitivity, 20-wk-old chow-fed rats were pretreated with a
      pharmacological PTP1B inhibitor 1 h before leptin, and 24-h food intake was
      recorded. As expected, leptin alone produced a small but nonsignificant reduction
      in food intake. However, pretreatment with the PTP1B inhibitor resulted in a
      marked improvement in leptin-dependent suppression of food intake (P < 0.05).
      These data are consistent with the hypothesis that increases in PTP1B contribute
      to hypothalamic leptin resistance as rats transition into middle age.

PMID- 17038558
TI  - Severity of the catabolic condition differentially modulates hypothalamic
      expression of growth hormone-releasing hormone in the fasted mouse: potential
      role of neuropeptide Y and corticotropin-releasing hormone.
AB  - To determine whether the severity of the catabolic condition differentially
      regulates the GH axis, male mice were either fed ad libitum or fasted for 12, 24,
      and 48 h. Hypothalami, pituitaries, and stomachs were collected for assessment of
      mRNA levels by quantitative real-time RT-PCR, and blood collected for measurement
      of plasma hormone and metabolite levels by commercial assay kits. Overnight (12
      h) fasting resulted in a significant suppression of circulating glucose, insulin,
      IGF-I, and leptin levels and an increase in corticosterone, free fatty acids, and
      n-octanoyl ghrelin levels, and these directional changes were maintained at the
      24- and 48-h time points. Fasting (24 h) also increased circulating GH levels,
      which was associated with an increase in pituitary mRNA levels for GHRH receptor
      and ghrelin receptor and a decrease in mRNA levels for somatostatin (SST)
      receptor (SSTR) subtypes, SSTR2, SSTR3, and SSTR5, where the changes in ghrelin
      receptor and SSTR expression persisted after 48 h fasting. Hypothalamic SST mRNA
      levels were not altered by fasting, whereas there was a transient rise in stomach
      SST mRNA levels 24 h after food withdrawal. In contrast, there was a biphasic
      effect of fasting on GHRH expression. GHRH mRNA levels were significantly
      elevated at 12 and 24 h but fell to approximately 50% of fed controls 48 h after
      food withdrawal. A sequential rise in hypothalamic neuropeptide Y (NPY) and CRH
      mRNA levels preceded the fall in GHRH expression, where fasting-induced changes
      in CRH and GHRH mRNA levels were not observed in 48-h-fasted NPY knockout mice.
      These observations, in light of previous reports showing both NPY and CRH can
      inhibit GHRH expression and GH release, suggest that these neuronal systems may
      work in concert to control the ultimate impact of fasting on GH axis function.

PMID- 17038559
TI  - Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy.
AB  - Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin
      expression, a negative regulator of muscle growth, is increased by
      glucocorticoids and myostatin overexpression is associated with lower muscle
      mass. This suggests that myostatin is required for the catabolic effects of
      glucocorticoids. We therefore investigated whether myostatin gene disruption
      could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout
      (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for
      10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose
      dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%;
      gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross
      sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice,
      there was no reduction of muscle mass nor fiber cross-sectional area after
      dexamethasone treatment. Muscle atrophy after 4 d of high-dose dexamethasone was
      associated with increased mRNA of enzymes involved in proteolytic pathways
      (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin
      like proteasomal activity. In contrast, the mRNA of these enzymes and the
      proteasomal activity were not significantly affected by dexamethasone in KO mice.
      Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this
      was associated with a potentially compensatory increase of IGF-II expression in
      both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion,
      our results show that myostatin deletion prevents muscle atrophy in
      glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced
      proteolysis, and suggest an important role of myostatin in muscle atrophy caused
      by glucocorticoids.

PMID- 17038560
TI  - Reversal of glucocorticoids-dependent proopiomelanocortin gene inhibition by
      leukemia inhibitory factor.
AB  - We previously have described molecular mechanisms converging at the Nur response
      element-signal transducer and activator of transcription (STAT) composite site
      responsible for synergistic activation of the proopiomelanocortin (POMC) gene
      promoter by leukemia inhibitory factor (LIF) and CRH. In this study, we asked how
      glucocorticoids (GC), the physiological negative regulators of POMC gene
      expression, modulate this synergism. In the corticotroph cell line AtT-20, the
      response of the wild-type promoter to LIF+CRH was barely inhibited by GC, whereas
      a distal promoter subregion (-414/-293) encompassing the Nur response element
      STAT site and devoid of the negative GC-responsive element located in the
      proximal domain, displayed a cooperative response to LIF+dexamethasone (DEX) and
      LIF+CRH+DEX treatments. LIF+CRH-stimulated ACTH secretion was also inefficiently
      inhibited by DEX in the same cell line. This study was focused thereafter on
      LIF+DEX cooperativity, which may be responsible, on the wild-type promoter, for
      lack of negative regulation by DEX of the LIF+CRH synergy. The STAT1-3 low
      affinity site, in the context of the (-414/-293) subregion of the POMC promoter,
      was found necessary and sufficient for transcriptional synergism between
      activated GC receptor (GR) and STAT1-3. Moreover the activities of reporters
      specific for STAT1-3 or GR were reciprocally enhanced by DEX or LIF. Single and
      sequential chromatin immunoprecipitations revealed 1) a STAT-dependent
      corecruitment of coactivators after LIF and LIF+DEX stimulation and 2) a more
      lasting recruitment of both STAT3 and GR in the same enhanceosome on the
      endogenous POMC promoter after LIF+DEX joint stimulation than after the single
      one. Such events may be responsible for a lack of repressive property of GR
      unmasked on the whole POMC promoter during LIF+CRH stimulation and may contribute
      to the tonicity of the hypothalamic-pituitary-adrenal axis during inflammatory
      infectious diseases.

PMID- 17038561
TI  - Apoptosis of rat granulosa cells after staurosporine and serum withdrawal is
      suppressed by adenovirus-directed overexpression of prohibitin.
AB  - Prohibitin (Phb1) is a highly conserved mitochondrial protein that is associated
      with granulosa cell differentiation, atresia, and luteolysis. Although prohibitin
      has been implicated in the suppression of apoptosis in mammalian cells, its
      specific role in programmed cell death in granulosa cells is unknown. In the
      present study, we examined the role of prohibitin in mediating staurosporine
      (STS) and serum withdrawal induced apoptosis in undifferentiated rat granulosa
      cells. Treatment of granulosa cells isolated from immature rat ovaries with STS
      and/or serum withdrawal induced a rapid decrease in the transmembrane potential
      of mitochondria, resulting in increased prohibitin content and induced apoptosis
      in a time- and dose-dependent manner. Infection of granulosa cells with a Phb1
      adenoviral construct resulted in overexpression of prohibitin that markedly
      attenuated the ability of STS and serum withdrawal to induce apoptosis via the
      intrinsic apoptotic pathway. To determine the site of action of Phb1, granulosa
      cells were transfected with a prohibitin-eGFP fusion construct, and the fusion
      protein expression patterns were analyzed by fluorescence microscopy and Western
      blot analysis of cell fractionated samples. These studies indicated that the
      prohibitin-eGFP fusion protein moved from the cytoplasm into the mitochondria.
      However, no prohibitin-eGFP fusion protein was observed in the nucleus in
      response to the STS-induced apoptotic stimulus. This result was corroborated by
      Western blot analysis with green fluorescent protein-specific antibody.
      Furthermore, the prohibitin-eGFP fusion protein also inhibited programmed cell
      death. These results provide evidence that prohibitin could serve an
      antiapoptotic role in undifferentiated granulosa cells.

PMID- 17038563
TI  - Contrasting evolution of expression differences in the testis between species and
      subspecies of the house mouse.
AB  - Regulatory changes in genes involved in reproduction are thought to be prime
      targets for divergence during speciation, since they are expected to play an
      important role in sexual selection and sexual conflict. We used microarray
      analysis of RNA from different wild populations of house mouse subspecies
      (including Mus m. musculus, Mus m. domesticus, and Mus m. castaneus) and from the
      sister species Mus spretus to test this assumption. A comparison of expression
      divergence in brain, liver/kidney, and testis shows a major difference in the
      evolutionary dynamics of testis-related genes. While the comparison between
      species confirms an excess in divergence in testis genes, we find that all
      comparisons between subspecies yield only a very small number of genes with
      significantly different expression levels in the testis. These results suggest
      that the early phase of the speciation process may not be driven by regulatory
      changes in genes that are potential targets of sexual selection, and that the
      divergence in these genes is only established during a later phase of the
      speciation process.

PMID- 17038564
TI  - Flexibility and constraint in the nucleosome core landscape of Caenorhabditis
      elegans chromatin.
AB  - Nucleosome positions within the chromatin landscape are known to serve as a major
      determinant of DNA accessibility to transcription factors and other interacting
      components. To delineate nucleosomal patterns in a model genetic organism,
      Caenorhabditis elegans, we have carried out a genome-wide analysis in which DNA
      fragments corresponding to nucleosome cores were liberated using an enzyme
      (micrococcal nuclease) with a strong preference for cleavage in non-nucleosomal
      regions. Sequence analysis of 284,091 putative nucleosome cores obtained in this
      manner from a mixed-stage population of C. elegans reveals a combined picture of
      flexibility and constraint in nucleosome positioning. As has previously been
      observed in studies of individual loci in diverse biological systems, we observe
      areas in the genome where nucleosomes can adopt a wide variety of positions in a
      given region, areas with little or no nucleosome coverage, and areas where
      nucleosomes reproducibly adopt a specific positional pattern. In addition to
      illuminating numerous aspects of chromatin structure for C. elegans, this
      analysis provides a reference from which to begin an investigation of
      relationships between the nucleosomal pattern, chromosomal architecture, and
      lineage-based gene activity on a genome-wide scale.

PMID- 17038568
TI  - Current trends in the management of iatrogenic cervical carotid artery injuries.
AB  - This study was undertaken to elicit the opinion of experts regarding the
      management of iatrogenic injury to the carotid artery. A text questionnaire was
      transmitted by electronic mail to members of the Western Vascular Society
      concerning management of iatrogenic injury to the cervical carotid artery.
      Participants were asked to submit information regarding practice status and their
      preferred choices for the management of different clinical scenarios. The
      scenarios were: (1) large bore sheath (> 8.5F) cannulation of the carotid artery
      in anesthetized patients, (2) large bore sheath cannulation of the carotid artery
      in an awake patient, (3) delayed recognition of a misplaced sheath by > 4 hours,
      and (4) arterial puncture was recognized after only the entry needle (16-gauge)
      was introduced but before sheath insertion. Finally, the members were asked to
      comment on the management of abnormal findings on duplex scanning, such as
      intimal flap or pseudoaneurysm. A response rate of 42% was obtained (45/106
      active members). Eighty-two percent of respondents had been in practice for
      longer than 10 years. Eighty-nine percent had seen this complication and 29% had
      cared for patients in whom subsequent neurologic deficit developed. The
      institutional incidence of such injury was 1-5 cases per year for 82% of
      respondents. Sixteen-gauge needle injury was managed by immediate removal and
      applied pressure by 98% of respondents. When large-bore sheath injury is
      recognized within 1 hour of insertion, 62% of respondents would remove the sheath
      and hold pressure, with or without obtaining a duplex ultrasound examination.
      However, if injury recognition was delayed for > 4 hours, 82% would proceed to
      surgery. Only 26% operated on asymptomatic carotid flap found on ultrasound,
      while the remaining 74% would base their decision on size and flow
      characteristics on ultrasound. The management of pseudoaneurysm differed
      significantly. Whereas 31% of respondents would manage this finding expectantly,
      69% would proceed to surgery regardless of size or symptoms. Despite awareness of
      iatrogenic injury to the cervical carotid artery, the institutional incidence
      remains high. Two thirds of respondents would manage a misplaced sheath in the
      carotid artery nonoperatively if the injury was recognized immediately. However,
      if injury recognition was delayed for > 4 hours, the majority of respondents
      would remove the sheath surgically. While the management of intimal flap largely
      depended on size and flow characteristics, 69% of respondents would operate on a
      pseudoaneurysm regardless of size or symptoms. The results of this survey may
      serve as a guideline for the management of this potentially devastating injury.

PMID- 17038569
TI  - Critical limb ischemia in the dialysis-dependent patient: infrainguinal vein
      bypass is justified.
AB  - The combination of critical limb ischemia and end-stage renal failure (ESRF, ie,
      dialysis- dependent) represents severe systemic atherosclerosis and is associated
      with a very poor medium-term survival. Many nephrologists and surgeons advocate
      primary amputation. We examined the recent experience in this unit to determine
      whether infrainguinal bypass in these patients can be justified. Retrospective
      study of all patients with critical limb ischemia and ESRF undergoing surgery in
      a regional vascular and renal unit between January 1996 and May 2003. Forty-two
      patients with ESRF (median age 65 years) were referred with critical limb
      ischemia. Seventeen patients underwent 24 (7 bilateral) infrainguinal bypasses
      (17 autologous vein, 7 polytetrafluoroethylene [PTFE] conduit; tissue loss in
      21/24, 88%), and 25 patients had primary major amputations of 32 limbs. Early
      occlusion occurred in 5 grafts (21%, all 5/5 PTFE). In-hospital mortality was 13%
      in the bypass group, 24% in the amputation group. Median in-hospital stay was 59
      days in the bypass group, 46 days in the amputation group. Thirty-day, 1- and 2
      year survival was 88%, 50%, and 33% in the bypass group; 83%, 39%, and 35% in the
      amputation group. The limb salvage rate was 66% at 1 year. Seventy-five percent
      (18/24) of operated on limbs (15/17 of vein grafts) avoided major amputation at
      follow-up (median 18 months) or death. The combination of critical limb ischemia
      and end- stage renal failure carries a poor medium-term survival independent of
      primary amputation or surgical revascularization. Infrainguinal bypass in
      selected cases with vein conduit can, however, allow the majority of these
      patients to avoid major limb amputation.

PMID- 17038566
TI  - Experimental validation of predicted mammalian erythroid cis-regulatory modules.
AB  - Multiple alignments of genome sequences are helpful guides to functional
      analysis, but predicting cis-regulatory modules (CRMs) accurately from such
      alignments remains an elusive goal. We predict CRMs for mammalian genes expressed
      in red blood cells by combining two properties gleaned from aligned, noncoding
      genome sequences: a positive regulatory potential (RP) score, which detects
      similarity to patterns in alignments distinctive for regulatory regions, and
      conservation of a binding site motif for the essential erythroid transcription
      factor GATA-1. Within eight target loci, we tested 75 noncoding segments by
      reporter gene assays in transiently transfected human K562 cells and/or after
      site-directed integration into murine erythroleukemia cells. Segments with a high
      RP score and a conserved exact match to the binding site consensus are validated
      at a good rate (50%-100%, with rates increasing at higher RP), whereas segments
      with lower RP scores or nonconsensus binding motifs tend to be inactive. Active
      DNA segments were shown to be occupied by GATA-1 protein by chromatin
      immunoprecipitation, whereas sites predicted to be inactive were not occupied. We
      verify four previously known erythroid CRMs and identify 28 novel ones. Thus,
      high RP in combination with another feature of a CRM, such as a conserved
      transcription factor binding site, is a good predictor of functional CRMs. Genome
      wide predictions based on RP and a large set of well-defined transcription factor
      binding sites are available through servers at http://www.bx.psu.edu/.

PMID- 17038565
TI  - Human heterochromatin proteins form large domains containing KRAB-ZNF genes.
AB  - Heterochromatin is important for gene regulation and chromosome structure, but
      the genes that are occupied by heterochromatin proteins in the mammalian genome
      are largely unknown. We have adapted the DamID method to systematically identify
      target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse
      cells. Unexpectedly, we found that CBX1 (formerly HP1beta) and SUV39H1 bind to
      genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional
      repressors. These genes constitute one of the largest gene families and are
      organized in clusters in the human genome. Preference of CBX1 for this gene
      family was observed in both human and mouse cells. High-resolution mapping on
      human chromosome 19 revealed that CBX1 coats large domains 0.1-4 Mb in size,
      which coincide with the position of KRAB-ZNF gene clusters. These domains show an
      intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the
      domains, it is absent from the promoters and binds more strongly to the 3' ends
      of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which
      may contribute to CBX1 recruitment. These results uncover a surprising link
      between heterochromatin and a large family of regulatory genes in mammals. We
      suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family.

PMID- 17038570
TI  - Techniques for preserving vertebral artery perfusion during thoracic aortic stent
      grafting requiring aortic arch landing.
AB  - Thoracic endografting offers many advantages over open repair. However, delivery
      of the device can be difficult and may necessitate adjunctive procedures. We
      describe our techniques for preserving perfusion to the left subclavian artery
      despite endograft coverage to obtain a proximal seal zone. We reviewed our
      experience with the Talent thoracic stent graft (Medtronic, Santa Rosa, CA). From
      1999 to 2003, 49 patients received this device (29 men, 20 women). Seventeen
      patients required adjunctive procedures to facilitate proximal graft placement.
      We performed left subclavian-to-left common carotid artery transposition (6),
      left common carotid-to-left subclavian artery bypass with ligation proximal to
      the vertebral artery (7), and left common carotid-to-left subclavian artery
      bypass with proximal coil embolization (4). Patients who had anatomy unfavorable
      to transposition or bypass with proximal ligation (large aneurysms or proximal
      vertebral artery origin) were treated with coil embolization of the proximal left
      subclavian artery in order to prevent subsequent type II endoleaks. Technical
      success rate of the carotid subclavian bypass was 100%. Patient follow-up ranged
      from 3 to 48 months with a mean of 12 months. Six patients had follow-up <6
      months owing to recent graft placement. Primary patency was 100%. No neurologic
      events occurred during the procedure or upon follow-up. One patient had a
      transient chyle leak that spontaneously resolved in 24 hours. Another patient had
      a phrenic nerve paresis that resolved after 3 weeks. We believe that it is
      important to maintain patency of the vertebral artery specifically when a patent
      right vertebral system and an intact basilar artery is not demonstrated.
      Furthermore, we describe a novel technique of coil embolization of the proximal
      left subclavian artery in conjunction with left common carotid-to-left subclavian
      artery bypass. This circumvents the need for potentially hazardous mediastinal
      dissection and ligation of the proximal left subclavian artery in cases of large
      proximal aneurysms or unfavorable vertebral artery anatomy.

PMID- 17038571
TI  - Evaluation of thrombogenicity by indium-111 platelet scintigraphy in endografting
      for abdominal aortic aneurysms.
AB  - Obstruction of the endograft limb by thrombosis has often been reported and may
      cause fatal complications such as leg necrosis or myonephropathic metabolic
      syndrome. The purpose of this study was to evaluate endograft antithrombogenicity
      by indium-111 platelet scintigraphy. Seventeen patients with abdominal aortic
      aneurysms were treated by endografting. Thirteen patients were treated with
      conventional open surgery using an artificial graft. The endograft was
      constructed from a self-expanding Z-shaped stent and woven polyester fabric.
      Autologous platelets labeled with indium-111 were injected at 2 weeks
      postoperatively. At 24 hours and 72 hours postinjection, the ratio of
      scintillation count of the endograft or graft to that of the native artery was
      calculated to assess platelet deposition. The normalization ratio was calculated
      as follows: (scintillation count per pixel of endograft or
      graft/circumference)/(scintillation count per pixel of the native femoral
      artery). Platelet factor 4 and beta-thromboglobulin were measured to evaluate the
      systemic platelets activity at 2 weeks postoperatively. There was no significant
      difference in platelet counts or labeling efficiency between the groups. The
      ratio was significantly higher in the endografting group than in the open surgery
      group at 72 hours postinjection (2.5-0.7 vs 3.9-1.1, P<.001). There was no
      significant difference in platelet factor 4 and beta-thromboglobulin between the
      groups. Although there was no difference in systemic platelet activity,
      endografting was associated with lower antithrombogenicity. It remains unclear
      whether lower antithrombogenicity causes thromboembolism as a complication of the
      procedure. The authors recommend the administration of antiplatelet drugs to
      prevent endograft obstruction in patients with very narrow iliac arteries.

PMID- 17038572
TI  - The Baltimore activity scale for intermittent claudication: a validation study.
AB  - The purpose of this study was to develop and cross-validate the Baltimore
      Activity Scale for Intermittent Claudication (BASIC) questionnaire in patients
      with peripheral arterial disease limited by intermittent claudication, and to
      determine whether the BASIC questionnaire score changed following a supervised
      program of exercise rehabilitation. A total of 702 consecutive patients with
      peripheral arterial disease and stable intermittent claudication were
      characterized on physical activity level using the BASIC questionnaire and an
      accelerometer. The first 351 patients tested were included in the validation
      group, whereas the final 351 patients were included in the cross-validation
      group. Subsequently, 61 of these patients participated in a randomized,
      controlled trial in which 28 patients completed 6 months of exercise
      rehabilitation and 24 patients completed usual care control. The sum of 5
      questions from the BASIC questionnaire (0-10 point scale) was predictive of daily
      physical activity using the following regression equation: Daily Physical
      Activity (kcal/day) = 102.2 + (49.6 x BASIC score); R = 0.76, R(2) = 0.58,
      standard error of estimate = 52.0 kcal/day, P < .0001. This equation was
      successfully cross-validated on an independent group of patients, as the
      predicted daily physical activity (339 - 181 kcal/day, mean - SD) was similar (P
      = .501) to measured daily physical activity (347 - 266 kcal/day, mean - SD).
      Furthermore, the BASIC score increased 38% following 6 months of exercise
      rehabilitation (P < .01), whereas no change was observed in the control group (P
      > .05). A composite of 5 questions obtained from the self-administered BASIC
      questionnaire accurately estimates daily physical activity in patients with
      peripheral arterial disease limited by intermittent claudication, and is
      sensitive to change in physical activity following a program of exercise
      rehabilitation.

PMID- 17038573
TI  - Iron deficiency in the acute-phase reaction after open aortic surgery.
AB  - The objective of this study was to quantify the magnitude of iron deficiency in
      the postoperative period after open aortic surgery. This was a prospective
      observational study in 55 consecutive patients. Blood samples were obtained on
      postoperative days 1, 2, 4, 30, and 45, and the parameters determined were the
      following: iron, transferrin, transferrin saturation index, transferrin-soluble
      receptor, ferritin, red cell count, hemoglobin, hematocrit, serum C-reactive
      protein, fibrinogen, mean corpuscular volume, mean corpuscular hemoglobin, mean
      corpuscular hemoglobin concentration, and number of blood units transfused. We
      performed statistical ANOVA test for repetitive measurements (lower bound) in
      regard to its basal level. Iron deficiency and its parameters reached the maximum
      at 48 hours postoperatively (iron: 18.92 g/dL and transferrin saturation index:
      11.1%) (P <.05). There was not a complete recovery after 45 days (iron: 51.23
      g/dL and transferrin saturation index: 18.0%) (P <.05). A similar evolution was
      observed in the other measured parameters (red cell count: 3.5 x 106/L.;
      hemoglobin: 10.4 g/dL; hematocrit: 30.7%) (P <.005), none affecting the values of
      concentration or volume (P <.05). Transferrin-soluble receptors, normal at first,
      were increased at postoperative days 30 and 45 (2.7 and 2.4 mg/dL respectively, P
      <.005). After open aortic surgery there is an important acute-phase reaction, a
      dramatic iron deficiency, and a lack of its transporters until the 45th analyzed
      day. The elevation of transferrin-soluble receptors in the 4th and 6th weeks
      denotes a necessity of iron supplementation for a correct development of the
      immature hematic cells since blood parameters do not reach normal levels in the
      6th postoperative week.

PMID- 17038574
TI  - Techniques for managing complications of arterial closure devices.
AB  - According to data reported by the American Heart Association, more than 5 million
      diagnostic and therapeutic catheterizations are performed each year in the United
      States. The number of catheterizations has tripled since 1979. It has been
      estimated that complications related to the access site result in more than
      75,000 surgical procedures annually. Thus, improved management of the access site
      itself is essential to achieve the greater goals of improved care and reduced
      cost. Manual compression directly over the site of arterial puncture usually
      results in adequate hemostasis but has several significant drawbacks. Manual
      compression is uncomfortable for the patient, is fatiguing and time-consuming for
      staff, and necessitates several hours of costly in-hospital observation. In
      addition, it may be ineffective in achieving hemostasis, especially in the
      setting of systemic anticoagulation or following the use of large-bore devices.
      Based on the perceived need for an improved method of managing the arterial
      access site following catheterization, various vascular sealing devices have been
      developed. There are at least 8 (and the number is increasing) hemostatic
      vascular closure devices that are currently approved by the FDA for access site
      closure after femoral arterial catheterization. The chief advantage attributed to
      vascular sealing devices is accelerated access site hemostasis, even in the
      setting of anticoagulation, leading to earlier ambulation and hospital discharge
      following arterial catheterization. The most important drawbacks related to
      vascular sealing devices include the cost of the devices and the possibility of
      increased access site complications. Despite the paucity of properly designed
      studies supporting their use, it is estimated that over one million vascular
      sealing devices are used annually in the United States, a number that has
      increased dramatically in the past 5 years.In this review, we present a brief
      description of the design and function of the most widely used devices, describe
      the most common mechanisms of failure, and recommend strategies for management of
      access site complications including hemorrhage, arterial obstruction, and
      infection.

PMID- 17038575
TI  - Endovascular repair of a symptomatic subclavian artery aneurysm in a patient with
      Marfan syndrome: a case report.
AB  - Endovascular techniques are being employed with increasing frequency in the
      management of peripheral arterial aneurysms. A 57-year-old patient with Marfan
      syndrome presented with a symptomatic 5 cm left subclavian artery aneurysm. He
      underwent successful endovascular exclusion of the aneurysm with immediate
      improvement of his symptoms. Duplex ultrasound 3 months after the procedure
      confirmed a patent graft and complete exclusion of the aneurysm.

PMID- 17038576
TI  - Endovascular coil embolization for large femoral false aneurysms: two case
      reports.
AB  - Ultrasound-guided compression and thrombin injections are reliable for the
      management of small and medium-sized false aneurysms. However, owing to technical
      limitations, large false aneurysms often necessitate surgical intervention, which
      is associated with significant postoperative morbidity and mortality.
      Endovascular coil embolization is an evolving minimally invasive technique that
      can be used as a safe option for large false femoral aneurysms. We report our
      experience with 2 cases of large false femoral aneurysms treated by using coils
      to occlude the aneurysm's feeding tract successfully.

PMID- 17038577
TI  - Cerebrospinal fluid drainage in the treatment of spontaneous spinal cord
      ischemia: a case report.
AB  - A patient with spontaneous acute spinal cord ischemia successfully treated with
      cerebrospinal fluid drainage is reported. There are no consensus guidelines on
      the management of spinal cord ischemia. Various preventive and rehabilitative
      measures have been suggested, but the best treatment remains unknown.

PMID- 17038578
TI  - Left renal vein reconstruction after right nephrectomy and inadvertent left renal
      vein ligation: a case report and review of the literature.
AB  - Left renal vein ligation has been used as a technical aid to gain exposure to the
      perirenal aorta and to control bleeding in abdominal aortic operations. Left
      renal vein ligation is considered to be well tolerated in patients with 2
      functioning kidneys, but has rarely been described in the setting of concomitant
      right nephrectomy and presents a management challenge. Some reports suggest
      recovery of renal function may be possible after left renal vein ligation during
      right nephrectomy, but other suggest that a delay in revascularizing the left
      renal venous drainage may result in irreversible nephropathy. This article
      reports the inadvertent division of the left renal vein during right nephrectomy.
      Renal failure ensued postoperatively. The left renal vein was reconstructed, and
      renal function was recovered. The inability to reliably predict which patients
      will have adverse outcome after left renal vein ligation in the setting of a
      right nephrectomy may necessitate preemptive intervention.

PMID- 17038579
TI  - Large uterine fibroids causing mechanical obstruction of the inferior vena cava
      and subsequent thrombosis: a case report.
AB  - A 35-year-old woman presented with severe left leg swelling and pain after a
      spontaneous abortion of a 20-week fetus. Duplex ultrasound imaging confirmed
      venous thrombosis of the left iliac, common femoral, superficial femoral, deep
      femoral, greater saphenous, posterior tibial, and popliteal, peroneal, and soleal
      veins. A computed tomography scan showed large uterine fibroids that were
      completely compressing the distal inferior vena cava and both ureters, with
      associated hydronephrosis. A magnetic resonance venography showed the inferior
      vena cava proximal to the mechanical obstruction was free of thrombosis but was
      dilated at 27 mm in the suprarenal location. A hysterectomy was performed and an
      8-pound uterus was removed. Intraoperative ultrasound of the inferior vena cava
      showed a patent crescent shaped vein with no thrombus and adequate venous blood
      flow. Pathology of the uterus showed a large leiomyoma with necrosis. Her lower
      extremity symptoms resolved.

PMID- 17038581
TI  - Interview with Dr. Heikki Rauvala regarding pivotal advance: analysis of
      proinflammatory activity of highly purified eukaryotic recombinant HMGB1
      (amphoterin). Interview by Marco E Bianchi.

PMID- 17038582
TI  - Impairment of T cell interactions with antigen-presenting cells by
      immunosuppressive drugs reveals involvement of calcineurin and NF-kappaB in
      immunological synapse formation.
AB  - A stable supramolecular cluster in T cells at the contact site of APCs, the
      immunological synapse (IS), is essential for full T cell activation. Failure of
      IS maturation, as determined by defective relocalization of the TCR/CD3 complex
      at the T cell/APC contact site, is linked with T cell hyporesponsiveness. The
      effects of clinically used immunosuppressants on these critical events, however,
      are undefined. Here, we show that treatment of T cells with cyclosporin A, FK506,
      and dexamethasone, which are known to inhibit calcineurin and NF-kappaB,
      respectively, but not rapamycin, the inhibitor of mammalian target of rapamycin,
      selectively prevented TCR/CD3 relocalization into the IS, while relocalization of
      adhesion and cytoskeletal proteins as well as T cell/APC conjugate formation
      remained unaltered. The involvement of calcineurin and NF-kappaB in IS maturation
      was confirmed by using specific inhibitors of these molecules (FR901725,
      gossypol, SN50). FK778, as an inhibitor of DNA replication and also TCR/CD3
      activated tyrosine kinases, globally abrogated cytoskeletal, adhesion, and
      signaling molecule relocalization, thereby preventing formation of an IS at an
      earlier, immature stage along with impaired, antigen-specific T cell/APC
      conjugate formation. Collectively, blocking IS formation at distinct stages may
      mediate effects on T cell activation of currently used immunosuppressants, apart
      from their capacity to block gene transcription, cytokine signaling, and DNA
      replication. Furthermore, these data imply novel functions of calcineurin and NF
      kappaB for successful IS maturation.

PMID- 17038583
TI  - Hereditary hemochromatosis results in decreased iron acquisition and growth by
      Mycobacterium tuberculosis within human macrophages.
AB  - Iron (Fe) acquisition is essential for the growth of intracellular Mycobacterium
      tuberculosis (M.tb). How this occurs is poorly understood. Hereditary
      hemochromatosis is an inherited disease in which most cells become overloaded
      with Fe. However, hereditary hemochromatosis macrophages have lower than normal
      levels of intracellular Fe. This suggests M.tb growth should be slower in those
      cells if macrophage intracellular Fe is used by M.tb. Therefore, we compared
      trafficking and acquisition of transferrin (Tf)- and lactoferrin (Lf)-chelated Fe
      by M.tb within the phagosome of monocyte-derived macrophages (MDM) from healthy
      controls and subjects with hereditary hemochromatosis. M.tb in both sets of
      macrophages acquired more Fe from Lf than Tf. Fe acquisition by M.tb within
      hereditary hemochromatosis macrophages was decreased by 84% from Tf and 92% from
      Lf relative to that in healthy control macrophages. There was no difference in Fe
      acquired from Tf and Lf by the two macrophage phenotypes. Both acquired 3 times
      more Fe from Lf than Tf. M.tb infection and incubation with interferon gamma (IFN
      gamma) reduced macrophage Fe acquisition by 20% and 50%, respectively. Both Tf
      and Lf colocalized with M.tb phagosomes to a similar extent, independent of
      macrophage phenotype. M.tb growth was 50% less in hereditary hemochromatosis
      macrophages. M.tb growing within macrophages from subjects with hereditary
      hemochromatosis acquire less Fe compared with healthy controls. This is
      associated with reduced growth of M.tb. These data support a role for macrophage
      intracellular Fe as a source for M.tb growth.

PMID- 17038586
TI  - Radar imaging of binary near-Earth asteroid (66391) 1999 KW4.
AB  - High-resolution radar images reveal near-Earth asteroid (66391) 1999 KW4 to be a
      binary system. The approximately 1.5-kilometer-diameter primary (Alpha) is an
      unconsolidated gravitational aggregate with a spin period approximately 2.8
      hours, bulk density approximately 2 grams per cubic centimeter, porosity
      approximately 50%, and an oblate shape dominated by an equatorial ridge at the
      object's potential-energy minimum. The approximately 0.5-kilometer secondary
      (Beta) is elongated and probably is denser than Alpha. Its average orbit about
      Alpha is circular with a radius approximately 2.5 kilometers and period
      approximately 17.4 hours, and its average rotation is synchronous with the long
      axis pointed toward Alpha, but librational departures from that orientation are
      evident. Exotic physical and dynamical properties may be common among near-Earth
      binaries.

PMID- 17038587
TI  - The phase-dependent infrared brightness of the extrasolar planet upsilon
      Andromedae b.
AB  - The star upsilon Andromedae is orbited by three known planets, the innermost of
      which has an orbital period of 4.617 days and a mass at least 0.69 that of
      Jupiter. This planet is close enough to its host star that the radiation it
      absorbs overwhelms its internal heat losses. Here, we present the 24-micrometer
      light curve of this system, obtained with the Spitzer Space Telescope. It shows a
      variation in phase with the orbital motion of the innermost planet, demonstrating
      that such planets possess distinct hot substellar (day) and cold antistellar
      (night) faces.

PMID- 17038588
TI  - Dynamical configuration of binary near-Earth asteroid (66391) 1999 KW4.
AB  - Dynamical simulations of the coupled rotational and orbital dynamics of binary
      near-Earth asteroid 66391 (1999 KW4) suggest that it is excited as a result of
      perturbations from the Sun during perihelion passages. Excitation of the mutual
      orbit will stimulate complex fluctuations in the orbit and rotation of both
      components, inducing the attitude of the smaller component to have large
      variation within some orbits and to hardly vary within others. The primary's
      proximity to its rotational stability limit suggests an origin from spin-up and
      disruption of a loosely bound precursor within the past million years.

PMID- 17038589
TI  - RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.
AB  - Double-stranded RNA (dsRNA) produced during viral replication is believed to be
      the critical trigger for activation of antiviral immunity mediated by the RNA
      helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma
      differentiation-associated gene 5 (MDA5). We showed that influenza A virus
      infection does not generate dsRNA and that RIG-I is activated by viral genomic
      single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the
      influenza protein nonstructured protein 1 (NS1), which is found in a complex with
      RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and
      potential target of viral immune evasion and suggest that its ability to sense 5'
      phosphorylated RNA evolved in the innate immune system as a means of
      discriminating between self and nonself.

PMID- 17038591
TI  - Funding basic agricultural research.

PMID- 17038590
TI  - 5'-Triphosphate RNA is the ligand for RIG-I.
AB  - The structural basis for the distinction of viral RNA from abundant self RNA in
      the cytoplasm of virally infected cells is largely unknown. We demonstrated that
      the 5'-triphosphate end of RNA generated by viral polymerases is responsible for
      retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules.
      Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate
      end or by nucleoside modification of RNA, both occurring during
      posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a
      negative-strand RNA virus and RNA prepared from virus-infected cells (but not
      from noninfected cells) triggered a potent interferon-alpha response in a
      phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus,
      uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be
      recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as
      the picornaviruses, serves as the molecular signature for the detection of viral
      infection by RIG-I.

PMID- 17038592
TI  - Genomics. On your mark. Get set. Sequence!

PMID- 17038593
TI  - Nuclear proliferation. North Korea's bomb: boom or bust?

PMID- 17038594
TI  - Nobel Prize in economics. Laurels for theories that demystified inflation,
      unemployment, and growth.

PMID- 17038595
TI  - Nobel Prize in chemistry. Solo winner detailed path From DNA to RNA.

PMID- 17038596
TI  - Biomedicine. NIH funds a dozen 'homes' for translational research.

PMID- 17038598
TI  - Fusion reactor. ITER's $12 billion gamble.

PMID- 17038597
TI  - Stem cells. California stem-cell institute unveils 10-year plan.

PMID- 17038599
TI  - Fusion reactor. How to squeeze a plasma.

PMID- 17038600
TI  - Brian O'Neill profile. Trying to lasso climate uncertainty.

PMID- 17038601
TI  - Neuroscience. Brain evolution on the far side.

PMID- 17038602
TI  - Public health. Gerberding defends her transformation of CDC.

PMID- 17038603
TI  - Particle physics. Tidy triangle dashes hopes for exotic undiscovered particles.

PMID- 17038604
TI  - Cooperating over water issues in the Middle East.

PMID- 17038605
TI  - What happens to the whistleblowers?

PMID- 17038606
TI  - A problem with mentoring.

PMID- 17038607
TI  - Mice, pain, and empathy.

PMID- 17038608
TI  - Ecology. Millennium ecosystem assessment: research needs.

PMID- 17038609
TI  - Genetics. The bacterial world gets smaller.

PMID- 17038610
TI  - Applied physics. Seeking the ultimate nanolaser.

PMID- 17038611
TI  - Cell biology. Balancing life-or-death decisions.

PMID- 17038612
TI  - Geochemistry. How fast does gold trickle out of volcanoes?

PMID- 17038613
TI  - Chemistry. Strong-arming molecular dynamics.

PMID- 17038614
TI  - Chemistry. Quantum chemistry of complex systems.

PMID- 17038616
TI  - Self-assembly of CdTe nanocrystals into free-floating sheets.
AB  - In their physical dimensions, surface chemistry, and degree of anisotropic
      interactions in solution, CdTe nanoparticles are similar to proteins. We
      experimentally observed their spontaneous, template-free organization into free
      floating particulate sheets, which resemble the assembly of surface layer (S
      layer) proteins. Computer simulation and concurrent experiments demonstrated that
      the dipole moment, small positive charge, and directional hydrophobic attraction
      are the driving forces for the self-organization process. The data presented here
      highlight the analogy of the solution behavior of the two vastly different
      classes of chemical structures.

PMID- 17038615
TI  - The 160-kilobase genome of the bacterial endosymbiont Carsonella.
AB  - Previous studies have suggested that the minimal cellular genome could be as
      small as 400 kilobases. Here, we report the complete genome sequence of the
      psyllid symbiont Carsonella ruddii, which consists of a circular chromosome of
      159,662 base pairs, averaging 16.5% GC content. It is by far the smallest and
      most AT-rich bacterial genome yet characterized. The genome has a high coding
      density (97%) with many overlapping genes and reduced gene length. Genes for
      translation and amino acid biosynthesis are relatively well represented, but
      numerous genes considered essential for life are missing, suggesting that
      Carsonella may have achieved organelle-like status.

PMID- 17038617
TI  - Dynamic stark control of photochemical processes.
AB  - A method is presented for controlling the outcome of photochemical reactions by
      using the dynamic Stark effect due to a strong, nonresonant infrared field. The
      application of a precisely timed infrared laser pulse reversibly modifies
      potential energy barriers during a chemical reaction without inducing any real
      electronic transitions. Dynamic Stark control (DSC) is experimentally
      demonstrated for a nonadiabatic photochemical reaction, showing substantial
      modification of reaction channel probabilities in the dissociation of IBr. The
      DSC process is nonperturbative and insensitive to laser frequency and affects all
      polarizable molecules, suggesting broad applicability.

PMID- 17038618
TI  - Rapid early development of circumarctic peatlands and atmospheric CH4 and CO2
      variations.
AB  - An analysis of 1516 radiocarbon dates demonstrates that the development of the
      current circumarctic peatlands began approximately 16.5 thousand years ago (ka)
      and expanded explosively between 12 and 8 ka in concert with high summer
      insolation and increasing temperatures. Their rapid development contributed to
      the sustained peak in CH4 and modest decline of CO2 during the early Holocene and
      likely contributed to CH4 and CO2 fluctuations during earlier interglacial and
      interstadial transitions. Given the decreased tempo of peatland initiation in the
      late Holocene and the transition of many from fens (which generated high levels
      of CH4) to ombrotrophic bogs, a neoglacial expansion of northern peatlands cannot
      explain the increase in atmospheric CH4 that occurred after 6 ka.

PMID- 17038619
TI  - Gold in magmatic hydrothermal solutions and the rapid formation of a giant ore
      deposit.
AB  - The Ladolam hydrothermal system, on Lihir Island, Papua New Guinea, hosts one of
      the youngest and largest gold deposits in the world. Several deep (more than 1
      kilometer) geothermal wells were drilled beneath the ore bodies to extract water
      at >275 degrees C and to facilitate open-pit mining. Using a titanium down-hole
      sampler, we determined that the deep geothermal brine of magmatic origin contains
      approximately 15 parts per billion gold. At the current gold flux of 24 kilograms
      per year, this deposit could have formed within approximately 55,000 years. The
      combination of sustained metal flux and efficient metal precipitation led to the
      formation of a giant hydrothermal gold deposit in a short period.

PMID- 17038620
TI  - Cellular and subcellular structure of neoproterozoic animal embryos.
AB  - Stereoblastic embryos from the Doushantuo Formation of China exhibit occasional
      asynchronous cell division, with diminishing blastomere volume as cleavage
      proceeded. Asynchronous cell division is common in modern embryos, implying that
      sophisticated mechanisms for differential cell division timing and embryonic cell
      lineage differentiation evolved before 551 million years ago. Subcellular
      structures akin to organelles, coated yolk granules, or lipid vesicles occur in
      these embryos. Paired reniform structures within embryo cells may represent
      fossil evidence of cells about to undergo division. Embryos exhibit no evidence
      of epithelial organization, even in embryos composed of approximately 1000 cells.
      Many of these features are compatible with metazoans, but the absence of
      epithelialization is consistent only with a stem-metazoan affinity for Doushantuo
      embryos.

PMID- 17038621
TI  - CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage.
AB  - The function of cyclin-dependent kinase 2 (CDK2) is often abolished after DNA
      damage. The inhibition of CDK2 plays a central role in DNA damage-induced cell
      cycle arrest and DNA repair. However, whether CDK2 also influences the survival
      of cells under genotoxic stress is unknown. Forkhead box O (FOXO) transcription
      factors are emerging as key regulators of cell survival. CDK2 specifically
      phosphorylated FOXO1 at serine-249 (Ser249) in vitro and in vivo. Phosphorylation
      of Ser249 resulted in cytoplasmic localization and inhibition of FOXO1. This
      phosphorylation was abrogated upon DNA damage through the cell cycle checkpoint
      pathway that is dependent on the protein kinases Chk1 and Chk2. Moreover,
      silencing of FOXO1 by small interfering RNA diminished DNA damage-induced death
      in both p53-deficient and p53-proficient cells. This effect was reversed by
      restored expression of FOXO1 in a manner depending on phosphorylation of Ser249.
      Functional interaction between CDK2 and FOXO1 provides a mechanism that regulates
      apoptotic cell death after DNA strand breakage.

PMID- 17038622
TI  - Tissue geometry determines sites of mammary branching morphogenesis in
      organotypic cultures.
AB  - The treelike structures of many organs, including the mammary gland, are
      generated by branching morphogenesis, a reiterative process of branch initiation
      and invasion from a preexisting epithelium. Using a micropatterning approach to
      control the initial three-dimensional structure of mouse mammary epithelial
      tubules in culture, combined with an algorithm to quantify the extent of
      branching, we found that the geometry of tubules dictates the position of
      branches. We predicted numerically and confirm experimentally that branches
      initiate at sites with a local minimum in the concentration of autocrine
      inhibitory morphogens, such as transforming growth factor-beta. These results
      reveal that tissue geometry can control organ morphogenesis by defining the local
      cellular microenvironment, a finding that has relevance to control of invasion
      and metastasis.

PMID- 17038623
TI  - Tandem riboswitch architectures exhibit complex gene control functions.
AB  - Riboswitches are structured RNAs typically located in the 5' untranslated regions
      of bacterial mRNAs that bind metabolites and control gene expression. Most
      riboswitches sense one metabolite and function as simple genetic switches.
      However, we found that the 5' region of the Bacillus clausii metE messenger RNA
      includes two riboswitches that respond to S-adenosylmethionine and coenzyme B12.
      This tandem arrangement yields a composite gene control system that functions as
      a two-input Boolean NOR logic gate. These findings and the discovery of
      additional tandem riboswitch architectures reveal how simple RNA elements can be
      assembled to make sophisticated genetic decisions without involving protein
      factors.

PMID- 17038624
TI  - A mutant chaperone converts a wild-type protein into a tumor-specific antigen.
AB  - Monoclonal antibodies have become important therapeutic agents against certain
      cancers. Many tumor-specific antigens are mutant proteins that are predominantly
      intracellular and thus not readily accessible to monoclonal antibodies. We found
      that a wild-type transmembrane protein could be transformed into a tumor-specific
      antigen. A somatic mutation in the chaperone gene Cosmc abolished function of a
      glycosyltransferase, disrupting O-glycan Core 1 synthesis and creating a tumor
      specific glycopeptidic neo-epitope consisting of a monosaccharide and a specific
      wild-type protein sequence. This epitope induced a high-affinity, highly
      specific, syngeneic monoclonal antibody with antitumor activity. Such tumor
      specific glycopeptidic neo-epitopes represent potential targets for monoclonal
      antibody therapy.

PMID- 17038625
TI  - A small microbial genome: the end of a long symbiotic relationship?
AB  - Intracellular bacteria are characterized by genome reduction. The 422,434-base
      pair genome of Buchnera aphidicola BCc, primary endosymbiont of the aphid Cinara
      cedri, is approximately 200 kilobases smaller than the previously sequenced B.
      aphidicola genomes. B. aphidicola BCc has lost most metabolic functions,
      including the ability to synthesize the essential amino acid tryptophan and
      riboflavin. In addition, most retained genes are evolving rapidly. Possibly, B.
      aphidicola BCc is losing its symbiotic capacity and is being complemented (and
      might be replaced) by the highly abundant coexisting secondary symbiont.

PMID- 17038626
TI  - TLRs in the Gut. III. Immune responses to flagellin in Crohn's disease: good,
      bad, or irrelevant?
AB  - Recent observations suggest that bacterial flagellin may be a target of the
      seemingly aberrant innate and adaptive immune responses that are associated with
      Crohn's disease. This article discusses the evidence that supports a role for
      flagellin in Crohn's disease and considers the potential roles of these responses
      in the pathophysiology of this disorder.

PMID- 17038627
TI  - Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2
      mediated choleresis and Nrf2-mediated antioxidative action in rat livers.
AB  - Inchinkoto (ICKT), a herbal medicine, has been recognized in Japan and China as a
      "magic bullet" for jaundice. To explore potent therapeutic agents for
      cholestasis, the effects of ICKT or its ingredients on multidrug resistance
      associated protein 2 (Mrp2/ MRP2)-mediated choleretic activity, as well as on
      antioxidative action, were investigated using rats and chimeric mice with livers
      that were almost completely repopulated with human hepatocytes. Biliary excretion
      of Mrp2 substrates and the protein mass, subcellular localization, and mRNA level
      of Mrp2 were assessed in rats after 1-wk oral administration of ICKT or genipin,
      a major ingredient of ICKT. Administration of ICKT or genipin to rats for 7 days
      increased bile flow and biliary excretion of bilirubin conjugates. Mrp2 protein
      and mRNA levels and Mrp2 membrane densities in the bile canaliculi and renal
      proximal tubules were significantly increased in ICKT- or genipin-treated rat
      livers and kidneys. ICKT and genipin, thereby, accelerated the disposal of
      intravenously infused bilirubin. The treatment also increased hepatic levels of
      heme oxygenase-1 and GSH by a nuclear factor-E2-related factor (Nrf2)-dependent
      mechanism. Similar effects of ICKT on MRP2 expression levels were observed in
      humanized livers of chimeric mice. In conclusion, these findings provide the
      rationale for therapeutic options of ICKT and its ingredients that should
      potentiate bilirubin disposal in vivo by enhancing Mrp2/MRP2-mediated secretory
      capacities in both livers and kidneys as well as Nrf2-mediated antioxidative
      actions in the treatment of cholestatic liver diseases associated with jaundice.

PMID- 17038628
TI  - Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of
      experimental hepatic fibrosis.
AB  - While CD8 subsets activate hepatic fibrosis, natural killer (NK) cells exhibit
      antifibrotic activity. Glatiramer acetate (GA) is an immune modulator for
      multiple sclerosis. We assessed the potential impact of GA on mouse hepatic
      fibrogenesis. Hepatic fibrosis was induced in C57BL/6 mice by intraperitoneal
      administration of carbon tetrachloride (CCl(4)) for 6 wk. During the last 2 wk,
      animals were also treated with either GA (200 mu/day ip) or medium and compared
      with naive and fibrotic mice (8 animals/group). GA markedly attenuated fibrosis
      without altering reactive oxygen species production. By morphometric measurement
      of Sirius red-stained tissue sections, the relative fibrosis area decreased from
      5.28 +/- 0.32% (mean +/- SE) in the untreated CCl(4) group to 2.01 +/- 0.28% in
      CCl(4)+GA-treated animals, compared with 0.38 +/- 0.07% in naive mice. alpha
      Smooth muscle actin immunoblotting and mRNA expression revealed a similar
      pattern. Serum aminotransferase and Ishak-Knodell necroinflammatory score were
      markedly elevated, to the same extent, in both CCl(4)-treated groups. Fibrosis
      induction was associated with significant increase in CD8 subsets and decrease in
      CD4 T cells. After GA treatment, however, NK content, CD4(+)CD25(+)FoxP3(+)
      cells, hepatic expression of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL), and apoptosis of hepatic stellate cells were all increased. Serum
      interleukin (IL)-10 levels markedly rose, whereas IL-4 fell. In vitro activation
      of human hepatic stellate cells cocultured with hepatitis C virus-derived
      peripheral blood lymphocytes decreased when lymphocytes were preincubated with GA
      before coculture. In an animal model of hepatic fibrosis, GA has an antifibrotic
      effect associated with decreased CD8 cells and reduced serum IL-4 levels and
      increased NK cells, CD4(+)CD25(+)FoxP3(+) cells, TRAIL, and elevated serum IL-10
      levels.

PMID- 17038629
TI  - Azoxymethane protects intestinal stem cells and reduces crypt epithelial mitosis
      through a COX-1-dependent mechanism.
AB  - Azoxymethane (AOM) is a potent DNA-damaging agent and carcinogen that induces
      intestinal and colonic tumors in rodents. Evaluation of the stem cell population
      by colony formation assay reveals that, within 8 h after treatment, AOM (10
      mg/kg) elicited a prosurvival response. In wild-type (WT) mice, AOM treatment
      induced a 2.5-fold increase in intestinal crypt stem cell survival. AOM treatment
      increased stem cell survival in cyclooxygenase (COX)-2(-/-) but not COX-1(-/-)
      mice, confirming a role of COX-1 in the AOM-induced increase in stem cell
      survival. COX-1 mRNA and protein expression as well as COX-1-derived PGE(2)
      synthesis were increased 8 h after AOM treatment. Immunohistochemical staining of
      COX-1 demonstrated expression of the enzyme in the crypt epithelial cells,
      especially in the columnar epithelial cells between the Paneth cells adjacent to
      the stem cell zone. WT mice receiving AOM exhibited increased intestinal
      apoptosis and a simultaneous reduction in crypt mitotic figures within 8 h of
      injection. There were no significant differences in baseline or AOM-induced
      intestinal epithelial apoptosis between WT and COX-1(-/-) mice, but there was a
      complete reversal of the AOM-mediated reduction in mitosis in COX-1(-/-) mice.
      This suggests that COX-1-derived PGE(2) may play a key role in the early phase of
      intestinal tumorigenesis in response to DNA damage and suggests that COX-1 may be
      a potential therapeutic target in this model of colon cancer.

PMID- 17038630
TI  - MEK-ERK inhibition corrects the defect in VLDL assembly in HepG2 cells: potential
      role of ERK in VLDL-ApoB100 particle assembly.
AB  - OBJECTIVE: Hepatic VLDL assembly is defective in HepG2 cells, resulting in the
      secretion of immature triglyceride-poor LDL-sized apoB particles. We investigated
      the mechanisms underlying defective VLDL assembly in HepG2 and have obtained
      evidence implicating the MEK-ERK pathway. METHODS AND RESULTS: HepG2 cells
      exhibited considerably higher levels of the ERK1/2 mass and activity compared
      with primary hepatocytes. Inhibition of ERK1/2 using the MEK1/MEK2 inhibitor,
      U0126 (but not the inactive analogue) led to a significant increase in apoB
      secretion. In the presence of oleic acid, ERK1/2 inhibition caused a major shift
      in the lipoprotein distribution with a majority of particles secreted as VLDL, an
      effect independent of insulin. In contrast, overexpression of constitutively
      active MEK1 decreased apoB and large VLDL secretion. MEK1/2 inhibition
      significantly increased both cellular and microsomal TG mass, and mRNA levels for
      DGAT-1 and DGAT-2. In contrast to ERK, modulation of the PI3-K pathway or
      inhibition of the p38 MAP kinase, had no effect on lipoprotein density profile.
      Modulation of the MEK-ERK pathway in primary hamster hepatocytes led to changes
      in apoB secretion and altered the density profile of apoB-containing
      lipoproteins. CONCLUSIONS: Inhibition of the overactive ras-MEK-ERK pathway in
      HepG2 cells can correct the defect in VLDL assembly leading to the secretion of
      large, VLDL-sized particles, similar to primary hepatocytes, implicating the MEK
      ERK cascade in VLDL assembly in the HepG2 model. Modulation of this pathway in
      primary hepatocytes also regulates apoB secretion and appears to alter the
      formation of VLDL-1 sized particles.

PMID- 17038631
TI  - Macrophage phospholipid transfer protein deficiency and ApoE secretion: impact on
      mouse plasma cholesterol levels and atherosclerosis.
AB  - OBJECTIVE: PLTP and apoE play important roles in lipoprotein metabolism and
      atherosclerosis. It is known that formation of macrophage-derived foam cells
      (which highly express PLTP and apoE) is the critical step in the process of
      atherosclerosis. We investigated the relationship between PLTP and apoE in
      macrophages and the atherogenic relevance in a mouse model. METHODS AND RESULTS:
      We transplanted PLTP-deficient mouse bone marrow into apoE-deficient mice (PLTP-/
      --> apoE-/-), creating a mouse model with PLTP deficiency and apoE expression
      exclusively in the macrophages. We found that PLTP-/- --> apoE-/- mice have
      significantly lower PLTP activity, compared with controls (WT --> apoE-/-; 20%,
      P<0.01). On a Western diet, PLTP-/- --> apoE-/- mice have significantly lower
      plasma apoE than that of WT --> apoE-/- mice (63%, P<0.001), and PLTP-deficient
      macrophages secrete significantly less apoE than WT macrophages (44%, P<0.01).
      Moreover, PLTP-/- --> apoE-/- mice have significantly higher plasma cholesterol
      (98%, P<0.001) and phospholipid (107%, P<0.001) than that of WT --> apoE-/- mice,
      thus increasing atherosclerotic lesions in the aortic arch and root (403%,
      P<0.001), as well as the entire aorta (298%, P<0.001). CONCLUSIONS: Macrophage
      PLTP deficiency causes a significant reduction of apoE secretion from the cells,
      and this in turn promotes the accumulation of cholesterol in the circulation and
      accelerates the development of atherosclerosis.

PMID- 17038632
TI  - Expression of LPL in endothelial-intact artery results in lipid deposition and
      vascular cell adhesion molecule-1 upregulation in both LPL and ApoE-deficient
      mice.
AB  - OBJECTIVE: Overexpression of lipoprotein lipase (LPL) in deendothelialized artery
      led to profound localized lipid deposition. In this study the role of LPL in
      atherogenesis in endothelial-intact carotid arteries was assessed in genetically
      hyperlipidemic LPL- and ApoE-deficient mice. METHODS AND RESULTS: Human wild-type
      LPL (hLPLwt), catalytically inactive LPL (hLPL194), or control alkaline
      phosphatase (hAP) were expressed in endothelial-intact carotid arteries via
      adenoviral vectors. Compared with Ad-hAP, lipid deposition in the arterial wall
      increased 10.0- and 5.1-fold for Ad-hLPLwt and Ad-hLPL194 in LPL-deficient mice,
      and 10.6- and 6.2-fold in ApoE-deficient mice, respectively. Vascular cell
      adhesion molecule-1 (VCAM-1) was upregulated in Ad-hLPLwt and Ad-hLPL194
      transferred arteries. CONCLUSIONS: Endothelial cell associated LPL, either active
      or inactive, in the arterial wall is a strong proatherosclerotic factor in both
      LPL- and ApoE-deficient mice.

PMID- 17038633
TI  - Macrophage low-density lipoprotein receptor-related protein deficiency enhances
      atherosclerosis in ApoE/LDLR double knockout mice.
AB  - OBJECTIVE: In vitro studies implicate that the low-density lipoprotein receptor
      (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In
      the present study, we investigated the in vivo role of macrophage specific LRP in
      atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND
      RESULTS: We generated macrophage-specific LRP-deficient mice on an apoE/LDLR
      double-deficient background. Macrophage LRP deletion did not affect plasma
      cholesterol and triglyceride levels, lipoprotein distribution, and blood monocyte
      counts. Nevertheless, macrophage LRP deficiency resulted in a 1.8-fold increase
      in total atherosclerotic lesion area in the aortic root of 18-week-old mice.
      Moreover, LRP deficiency also resulted in a relatively higher number of advanced
      lesions. Whereas macrophage and smooth muscle cell content did not differ between
      LRP-deficient mice and control littermates, a 1.7-fold increase in collagen
      content and 2.3-fold decrease in relative number of CD3+ T cells were observed in
      lesions from macrophage specific LRP-deficient mice. CONCLUSIONS: Our data
      demonstrate that independent of its role in lipoprotein uptake, absence of LRP in
      macrophages resulted in more advanced atherosclerosis and in lesions that
      contained more collagen and less CD3+ T cells. In contrast to previous in vitro
      studies, we conclude that macrophage LRP has an atheroprotective potential and
      may modulate the extracellular matrix in the atherosclerotic lesions.

PMID- 17038634
TI  - Circulating leukocyte-derived microparticles predict subclinical atherosclerosis
      burden in asymptomatic subjects.
AB  - OBJECTIVE: To clarify circulating microparticles (MP) relationships with
      preclinical atherosclerosis. METHODS AND RESULTS: In 216 subjects without
      cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived,
      endothelium-derived and leukocyte-derived circulating MP by capture on annexin V,
      anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2)
      Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors
      measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound
      examination of carotid, abdominal aorta, and femoral arteries. Number of sites
      with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2
      to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in
      the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome
      (P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease
      (P<0.01), and correlated positively with number of metabolic syndrome components
      (P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites
      (P<0.01). In multivariate analysis, 2- to 3-sites disease was independently
      associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001),
      and metabolic syndrome (P<0.01). None of the other MP types correlated with risk
      markers or atherosclerosis. CONCLUSIONS: Leukocyte-derived MP, identified by
      affinity for CD11a, are increased in subjects with ultrasound evidence of
      subclinical atherosclerosis, unveiling new directions for atherosclerosis
      research.

PMID- 17038635
TI  - Plasma adiponectin levels in relation to carotid intima media thickness and
      markers of insulin resistance.
AB  - BACKGROUND: Circulating adiponectin is a marker for insulin sensitivity, derived
      from fat cells. It is largely unknown if adiponectin is also an independent
      marker for early atherosclerosis. METHODS AND RESULTS: Plasma adiponectin levels
      were measured in 373 men and 514 women of middle-age by a time-resolved
      immunofluorometric assay. The subjects were sampled stratified for degree of
      insulin sensitivity (HOMA-IR). An ultrasound measurement of the right common
      carotid artery intima media thickness (IMT) was made. When the distribution of
      adiponectin was stratified into sex-specific quartiles (Q1 to Q4), men in Q4
      differed from Q1 in higher mean age and high-density lipoprotein (HDL)
      cholesterol, but lower blood pressure, HbA1c, HOMA-index, and body mass index.
      Women showed similar associations. Mean IMT for men was significantly lower
      (P=0.03) in adiponectin Q4 as compared with Q1 when adjusted for age, waist,
      smoking, HDL cholesterol, and diastolic blood pressure. When adding HbA1c and
      HOMA to the model, the association was no longer significant (P=0.15). In women
      no difference in IMT was noticed across adiponectin quartiles. CONCLUSIONS:
      Plasma adiponectin is a marker of glucose metabolism and obesity and shows an
      inverse age-adjusted association with carotid ultrasound IMT in men, but not in
      women. This association is attenuated after adjustments for other risk factors.

PMID- 17038636
TI  - Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in
      type 2 diabetes.
AB  - OBJECTIVE: Receptor for advanced glycation end products (AGEs) (RAGE) plays a
      central role in the process of plaque rupture in diabetic patients. Recently, it
      has been reported that RAGE may be downregulated by improving glycemic control.
      In contrast, despite being well known that RAGE may be induced in human vessels
      in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE
      generation, no data exist regarding the possibility of a pharmacological
      modulation of glucose-independent RAGE generation. Thus, the aim of this study
      was to characterize the effect of simvastatin on the expression of RAGE and RAGE
      dependent plaque-destabilizing genes in human atherosclerotic plaques. METHODS
      AND RESULTS: Seventy type 2 diabetic patients with asymptomatic carotid artery
      stenosis (>70%) were randomized to American Heart Association (AHA) step 1 diet
      plus simvastatin (40 mg/d) or AHA step 1 diet alone for 4 months before
      endarterectomy. Plaque expression of MPO, AGEs, RAGE, NF-kappaB, COX-2, mPGES-1,
      matrix metalloproteinase (MMP)-2 and MMP-9, lipid and oxidized LDL (oxLDL)
      content, procollagen 1, and interstitial collagen was analyzed by
      immunohistochemistry and Western blot; zymography was used to detect MMP
      activity. Plaques from the simvastatin group had less (P<0.0001) immunoreactivity
      for MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, and MMP-9, lipids and oxLDL;
      reduced (P<0.0001) gelatinolytic activity; increased (P<0.0001) procollagen 1 and
      collagen content; and fewer (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+
      cells. Of interest, RAGE inhibition by simvastatin, observed not only in plaque
      sections but also in plaque-derived macrophages, was reverted by addition of AGEs
      in vitro. CONCLUSIONS: This study supports the hypothesis that simvastatin
      inhibits plaque RAGE expression by decreasing MPO-dependent AGE generation. This
      effect in turn might contribute to plaque stabilization by inhibiting the
      biosynthesis of PGE2-dependent MMPs, responsible for plaque rupture.

PMID- 17038637
TI  - Apolipoprotein CIII-induced THP-1 cell adhesion to endothelial cells involves
      pertussis toxin-sensitive G protein- and protein kinase C alpha-mediated nuclear
      factor-kappaB activation.
AB  - OBJECTIVE: Plasma apolipoprotein CIII (apoCIII) independently predicts risk for
      coronary heart disease (CHD). We recently reported that apoCIII directly enhances
      adhesion of human monocytes to endothelial cells (ECs), and identified the
      activation of PKC alpha as a necessary upstream event of enhanced monocyte
      adhesion. This study tested the hypothesis that apoCIII activates PKC alpha in
      human monocytic THP-1 cells, leading to NF-kappaB activation. METHODS AND
      RESULTS: Among inhibitors specific to PKC activators, phosphatidylcholine
      specific phospholipase C (PC-PLC) inhibitor D609 limited apoCIII-induced PKC
      alpha activation and THP-1 cell adhesion. ApoCIII increased PC-PLC activity in
      THP-1 cells, resulting in PKC alpha activation. Pertussis toxin (PTX) inhibited
      apoCIII-induced PC-PLC activation and subsequent PKC alpha activation,
      implicating PTX-sensitive G protein pathway. ApoCIII further activated nuclear
      factor-kappaB (NF-kappaB) through PKC alpha in THP-1 cells and augmented beta1
      integrin expression. The NF-kappaB inhibitor peptide SN50 partially inhibited
      apoCIII-induced beta1-integrin expression and THP-1 cell adhesion. ApoCIII-rich
      VLDL had similar effects to apoCIII alone. CONCLUSIONS: PTX-sensitive G protein
      pathway participates critically in PKC alpha stimulation in THP-1 cells exposed
      to apoCIII, activating NF-kappaB, and increasing beta1-integrin. This action
      causes monocytic cells to adhere to endothelial cells. Furthermore, because
      leukocyte NF-kappaB activation contributes to inflammatory aspects of
      atherogenesis, apoCIII may stimulate diverse inflammatory responses through
      monocyte activation.

PMID- 17038638
TI  - Physical activity improves long-term stroke outcome via endothelial nitric oxide
      synthase-dependent augmentation of neovascularization and cerebral blood flow.
AB  - Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves
      endothelium function, and protects from vascular disease. Here, we tested whether
      voluntary running would enhance neovascularization and long-term recovery
      following mild brain ischemia. Wild-type mice were exposed to 30 minutes of
      middle-cerebral artery occlusion (MCAo) and reperfusion. Continuous voluntary
      running on wheels conferred long-term upregulation of eNOS in the vasculature and
      of endothelial progenitor cells (EPCs) in the spleen and bone marrow (BM). This
      was associated with higher numbers of circulating EPCs in the blood and enhanced
      neovascularization. Moreover, engraftment of TIE2/LacZ-positive BM-derived cells
      was increased in the ischemic brain. Four weeks after the insult, trained animals
      showed higher numbers of newly generated cells in vascular sites, increased
      density of perfused microvessels and sustained augmentation of cerebral blood
      flow within the ischemic striatum. Moreover, running conferred tissue sparing and
      improved functional outcome at 4 weeks. The protective effects of running on
      angiogenesis and outcome were completely abolished when animals were treated with
      a NOS inhibitor or the antiangiogenic compound endostatin after brain ischemia,
      and in animals lacking eNOS expression. Voluntary physical activity improves long
      term stroke outcome by eNOS-dependent mechanisms related to improved angiogenesis
      and cerebral blood flow.

PMID- 17038639
TI  - ATP release from activated neutrophils occurs via connexin 43 and modulates
      adenosine-dependent endothelial cell function.
AB  - Extracellular ATP liberated during hypoxia and inflammation can either signal
      directly on purinergic receptors or can activate adenosine receptors following
      phosphohydrolysis to adenosine. Given the association of polymorphonuclear
      leukocytes (PMNs) with adenine-nucleotide/nucleoside signaling in the
      inflammatory milieu, we hypothesized that PMNs are a source of extracellular ATP.
      Initial studies using high-performance liquid chromatography and luminometric ATP
      detection assays revealed that PMNs release ATP through activation-dependent
      pathways. In vitro models of endothelial barrier function and
      neutrophil/endothelial adhesion indicated that PMN-derived ATP signals through
      endothelial adenosine receptors, thereby promoting endothelial barrier function
      and attenuating PMN/endothelial adhesion. Metabolism of extracellular ATP to
      adenosine required PMNs, and studies addressing these metabolic steps revealed
      that PMN express surface ecto-apyrase (CD39). In fact, studies with PMNs derived
      from cd39(-/-) mice showed significantly increased levels of extracellular ATP
      and lack of ATP dissipation from their supernatants. After excluding lytic ATP
      release, we used pharmacological strategies to reveal a potential mechanism
      involved in PMN-dependent ATP release (eg, verapamil, dipyridamole, brefeldin A,
      18-alpha-glycyrrhetinic acid, connexin-mimetic peptides). These studies showed
      that PMN ATP release occurs through connexin 43 (Cx43) hemichannels in a
      protein/phosphatase-A-dependent manner. Findings in human PMNs were confirmed in
      PMNs derived from induced Cx43(-/-) mice, whereby activated PMNs release less
      than 15% of ATP relative to littermate controls, whereas Cx43 heterozygote PMNs
      were intermediate in their capacity for ATP release (P<0.01). Taken together, our
      results identify a previously unappreciated role for Cx43 in activated PMN ATP
      release, therein contributing to the innate metabolic control of the inflammatory
      milieu.

PMID- 17038640
TI  - Cyclic AMP imaging in adult cardiac myocytes reveals far-reaching beta1
      adrenergic but locally confined beta2-adrenergic receptor-mediated signaling.
AB  - Beta(1)- and beta(2)-adrenergic receptors (betaARs) are known to differentially
      regulate cardiomyocyte contraction and growth. We tested the hypothesis that
      these differences are attributable to spatial compartmentation of the second
      messenger cAMP. Using a fluorescent resonance energy transfer (FRET)-based
      approach, we directly monitored the spatial and temporal distribution of cAMP in
      adult cardiomyocytes. We developed a new cAMP-FRET sensor (termed HCN2-camps)
      based on a single cAMP binding domain of the hyperpolarization activated cyclic
      nucleotide-gated potassium channel 2 (HCN2). Its cytosolic distribution, high
      dynamic range, and sensitivity make HCN2-camps particularly well suited to
      monitor subcellular localization of cardiomyocyte cAMP. We generated HCN2-camps
      transgenic mice and performed single-cell FRET imaging on freshly isolated
      cardiomyocytes. Whole-cell superfusion with isoproterenol showed a moderate
      elevation of cAMP. Application of various phosphodiesterase (PDE) inhibitors
      revealed stringent control of cAMP through PDE4>PDE2>PDE3. The beta(1)AR-mediated
      cAMP signals were entirely dependent on PDE4 activity, whereas beta(2)AR-mediated
      cAMP was under control of multiple PDE isoforms. beta(1)AR subtype-specific
      stimulation yielded approximately 2-fold greater cAMP responses compared with
      selective beta(2)-subtype stimulation, even on treatment with the nonselective
      PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) (DeltaFRET, 17.3+/-1.3%
      [beta(1)AR] versus 8.8+/-0.4% [beta(2)AR]). Treatment with pertussis toxin to
      inactivate G(i) did not affect cAMP production. Localized beta(1)AR stimulation
      generated a cAMP gradient propagating throughout the cell, whereas local
      beta(2)AR stimulation did not elicit marked cAMP diffusion. Our data reveal that
      in adult cardiac myocytes, beta(1)ARs induce far-reaching cAMP signals, whereas
      beta(2)AR-induced cAMP remains locally confined.

PMID- 17038641
TI  - Time course of degradation of cardiac troponin I in patients with acute ST
      elevation myocardial infarction: the ASSENT-2 troponin substudy.
AB  - Although measurement of troponin is widely used for diagnosing acute myocardial
      infarction (AMI), its diagnostic potential may be increased by a more complete
      characterization of its molecular appearance and degradation in the blood. The
      aim of this study was to define the time course of cardiac troponin I (cTnI)
      degradation in patients with acute ST-elevation myocardial infarction (STEMI). In
      the ASSENT-2 substudy, 26 males hospitalized with STEMI were randomized to 2
      different thrombolytic drugs within 6 hours after onset of symptoms. Blood
      samples were obtained just before initiation of thrombolysis and at 30 minutes
      intervals (7 samples per patient). Western blot analysis was performed using anti
      cTnI antibodies and compared with serum concentrations of cTnI. All patients
      exceeded the cTnI cutoff for AMI during the sampling period; at initiation of
      therapy, 23 had elevated cTnI values. All patients demonstrated 2 bands on
      immunoblot: intact cTnI and a single degradation product as early as 90 minutes
      after onset of symptoms. On subsequent samples, 15 of 26 patients showed multiple
      degradation products with up to 7 degradation bands. The appearance of fragments
      was correlated with higher levels of cTnI (P<0.001) and time to initiation of
      treatment (P=0.058). This study defines for the first time the initial time
      course of cTnI degradation in STEMI. Intact cTnI and a single degradation product
      were detectable on immunoblot as early as 90 minutes after onset of symptoms with
      further degradation after 165 minutes. Infarct size and time to initiation of
      treatment was the major determinant for degradation.

PMID- 17038642
TI  - Adenosine restores angiotensin II-induced contractions by receptor-independent
      enhancement of calcium sensitivity in renal arterioles.
AB  - Adenosine is coupled to energy metabolism and regulates tissue blood flow by
      modulating vascular resistance. In this study, we investigated isolated, perfused
      afferent arterioles of mice, which were subjected to desensitization during
      repeated applications of angiotensin II. Exogenously applied adenosine restores
      angiotensin II-induced contractions by increasing calcium sensitivity of the
      arterioles, along with augmented phosphorylation of the regulatory unit of the
      myosin light chain. Adenosine restores angiotensin II-induced contractions via
      intracellular action, because inhibition of adenosine receptors do not prevent
      restoration, but inhibition of NBTI sensitive adenosine transporters does.
      Restoration was prevented by inhibition of Rho-kinase, protein kinase C, and the
      p38 mitogen-activated protein kinase, which modulate myosin light chain
      phosphorylation and thus calcium sensitivity in the smooth muscle. Furthermore,
      adenosine application increased the intracellular ATP concentration in LuciHEK
      cells. The results of the study suggest that restoration of the angiotensin II
      induced contraction by adenosine is attributable to the increase of the calcium
      sensitivity by phosphorylation of the myosin light chain. This can be an
      important component of vascular control during ischemic and hypoxic conditions.
      Additionally, this mechanism may contribute to the mediation of the
      tubuloglomerular feedback by adenosine in the juxtaglomerular apparatus of the
      kidney.

PMID- 17038643
TI  - Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in
      tumor necrosis factor-alpha transgenic mice.
AB  - Innate immunity promotes both the generation of autoimmunity and immunoregulation
      of adaptive immunity. Transgenic mice expressing the tumor necrosis factor-alpha
      (TNF-alpha) gene under the cardiac myosin promoter (TNF1.6 mice) develop dilated
      cardiomyopathy. Transgenic mice show extensive cardiac inflammation, suggesting
      that immunopathogenic mechanisms may promote cardiomyopathy. Two coxsackievirus
      B3 (CVB3) variants infect and replicate in the heart. H3 variant is highly
      myocarditic, but H310A1 variant activates CD4(+) T regulatory cells, which
      protect against viral myocarditis. T-cell depletion of TNF1.6 mice using
      monoclonal anti-CD3 or anti-CD4 antibody significantly reduced heart size and
      plasma troponin I concentrations compared with control TNF1.6 mice.
      Cardiomyopathy in TNF1.6 mice correlates to a CD4(+)Th1 response and autoimmune
      IgG2a antibodies. TNF1.6 mice infected with H310A1 virus reduced heart size and
      cardiac inflammation corresponding to the activation of CD4(+)CD25(+)FoxP3(+) (T
      regulatory cells). Immunosuppression is dependent on IL-10 but not TGFbeta.
      Adoptive transfer of the CD4(+)CD25(+) cells from H310A1-infected mice into
      uninfected TNF1.6 recipients abrogated cardiomyopathy. Exogenous administration
      of recombinant TNF-alpha to H310A1-infected mice for 4 days abrogated
      immunosuppression. Cardiac enlargement in TNF1.6 mice is partly attributable to T
      cell activation and humoral autoimmunity caused by cytokine expression. T
      regulatory cells induced by H310A1 virus abrogate autoimmunity caused by TNF
      alpha overexpression. H3 virus infection induces high levels of systemic TNF
      alpha, whereas H310A1 virus does not. The low TNF-alpha response during H310A1
      infections is likely responsible for the T regulatory cell response in these
      animals.

PMID- 17038645
TI  - Plaque angiogenesis versus compensatory arteriogenesis in atherosclerosis.

PMID- 17038644
TI  - Calmodulin kinase II inhibition shortens action potential duration by
      upregulation of K+ currents.
AB  - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is
      activated by elevated intracellular Ca(2+) (Ca(2+)(i)), and mice with chronic
      myocardial CaMKII inhibition (Inh) resulting from transgenic expression of a
      CaMKII inhibitory peptide (AC3-I) unexpectedly showed action potential duration
      (APD) shortening. Inh mice exhibit increased L-type Ca(2+) current (I(Ca)),
      because of upregulation of protein kinase A (PKA) activity, and decreased CaMKII
      dependent phosphorylation of phospholamban (PLN). We hypothesized that CaMKII is
      a molecular signal linking Ca(2+)(i) to repolarization. Whole cell voltage-clamp
      recordings revealed that the fast transient outward current (I(to,f)) and the
      inward rectifier current (I(K1)) were selectively upregulated in Inh, compared
      with wild-type (WT) and transgenic control, mice. Breeding Inh mice with mice
      lacking PLN returned I(to,f) and I(K1) to control levels and equalized the APD
      and QT intervals in Inh mice to control and WT levels. Dialysis of AC3-I into WT
      cells did not result in increased I(to,f) or I(K1), suggesting that enhanced
      cardiac repolarization in Inh mice is an adaptive response to chronic CaMKII
      inhibition rather than an acute effect of reduced CaMKII activity. Increasing PKA
      activity, by cell dialysis with cAMP, or inhibition of PKA did not affect I(K1)
      in WT cells. Dialysis of WT cells with cAMP also reduced I(to,f), suggesting that
      PKA upregulation does not increase repolarizing K(+) currents in Inh mice. These
      findings provide novel in vivo and cellular evidence that CaMKII links Ca(2+)(i)
      to cardiac repolarization and suggest that PLN may be a critical CaMKII target
      for feedback regulation of APD in ventricular myocytes.

PMID- 17038646
TI  - A single second messenger: several possible cellular responses depending on
      distinct subcellular pools.

PMID- 17038647
TI  - A new paradigm: calcium independent and caveolae internalization dependent
      release of nitric oxide by the endothelial nitric oxide synthase.

PMID- 17038648
TI  - New insights in the role of cardiac myosin binding protein C as a regulator of
      cardiac contractility.

PMID- 17038649
TI  - Signaling mechanisms in ischemic preconditioning: interaction of PKCepsilon and
      MitoK(ATP) in the inner membrane of mitochondria.

PMID- 17038650
TI  - Allograft vasculopathy versus atherosclerosis.
AB  - Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream
      therapy for heart failure. Approximately half of patients needing HTx have organ
      failure consequent to atherosclerosis. Despite advances in immunosuppressive
      drugs, long-term success of HTx is limited by the development of a particular
      type of coronary atherosclerosis, referred to as cardiac allograft vasculopathy
      (CAV). Although the exact pathogenesis of CAV remains to be established, there is
      strong evidence that CAV involves immunologic mechanisms operating in a milieu of
      nonimmunologic risk factors. The immunologic events constitute the principal
      initiating stimuli, resulting in endothelial injury and dysfunction, altered
      endothelial permeability, with consequent myointimal hyperplasia and
      extracellular matrix synthesis. Lipid accumulation in allograft arteries is
      prominent, with lipoprotein entrapment in the subendothelial tissue, through
      interactions with proteoglycans. The apparent endothelial "intactness" in human
      coronary arteries of the transplanted heart suggest that permeability and
      function of the endothelial barrier altered. Various insults to the vascular bed
      result in vascular smooth muscle cell (SMC) activation. Activated SMCs migrate
      from the media into the intima, proliferate, and elaborate cytokines and
      extracellular matrix proteins, resulting in luminal narrowing and impaired
      vascular function. Arteriosclerosis is a broad term that is used to encompass all
      diseases that lead to arterial hardening, including native atherosclerosis,
      postangioplasty restenosis, vein bypass graft occlusion, and CAV. These diseases
      exhibit many similarities; however, they are distinct from one another in
      numerous ways as well. The present review summarizes the current understanding of
      the risk factors and the pathophysiological similarities and differences between
      CAV and atherosclerosis.

PMID- 17038651
TI  - Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic
      nucleotide phosphodiesterases.
AB  - A current challenge in cellular signaling is to decipher the complex
      intracellular spatiotemporal organization that any given cell type has developed
      to discriminate among different external stimuli acting via a common signaling
      pathway. This obviously applies to cAMP and cGMP signaling in the heart, where
      these cyclic nucleotides determine the regulation of cardiac function by many
      hormones and neuromediators. Recent studies have identified cyclic nucleotide
      phosphodiesterases as key actors in limiting the spread of cAMP and cGMP, and in
      shaping and organizing intracellular signaling microdomains. With this new role,
      phosphodiesterases have been promoted from the rank of a housekeeping attendant
      to that of an executive officer.

PMID- 17038652
TI  - Antihypertensive treatment in reducing the risk of dementia.

PMID- 17038653
TI  - Migraine relief after patent foramen ovale closure: should vascular risk factor
      control be achieved first?

PMID- 17038654
TI  - Previous cardiac abnormalities in subarachnoid hemorrhage may also have
      background genetic polymorphisms.

PMID- 17038655
TI  - Asymmetric dimethylarginine and cerebrovascular disorders in humans.

PMID- 17038659
TI  - Tuberculosis among foreign-born persons in the United States: achieving
      tuberculosis elimination.
AB  - RATIONALE: In the United States, the number of annual reported cases of
      tuberculosis (TB) among U.S.-born persons declined by 62% from 1993 to 2004, but
      increased by 5% among foreign-born persons. Over half of all reported cases of TB
      in the United States occur among foreign-born persons, most of these due to
      activation of latent TB infection (LTBI). Current guidelines recommend targeting
      only foreign-born persons who entered the United States within the previous 5 yr
      for LTBI testing. OBJECTIVE: We sought to assess the epidemiologic basis for this
      guideline. METHODS: We calculated TB case rates among foreign-born persons,
      stratified by duration of United States residence and world region of origin. We
      determined the number of cases using 2004 U.S. TB surveillance data, and
      calculated case rates using population data from the 2004 American Community
      Survey. MEASUREMENTS AND MAIN RESULTS: In 2004, a total of 14,517 cases of TB
      were reported; 3,444 (24%) of these were among foreign-born persons who had
      entered the United States more than 5 yr previously. The rate of TB disease among
      foreign-born persons was 21.5/100,000, compared with 2.7/100,000 for U.S.-born
      persons, and varied by duration of residence and world region of origin.
      CONCLUSIONS: Almost one-quarter of all TB cases in the United States occur among
      foreign-born persons who have resided in the United States for longer than 5 yr;
      case rates for such persons from selected regions of origin remain substantially
      elevated. To eliminate TB, we must address the burden of LTBI in this high-risk
      group.

PMID- 17038660
TI  - Tidal hyperinflation during low tidal volume ventilation in acute respiratory
      distress syndrome.
AB  - RATIONALE: Tidal volume and plateau pressure limitation decreases mortality in
      acute respiratory distress syndrome. Computed tomography demonstrated a small,
      normally aerated compartment on the top of poorly aerated and nonaerated
      compartments that may be hyperinflated by tidal inflation. OBJECTIVES: We
      hypothesized that despite tidal volume and plateau pressure limitation, patients
      with a larger nonaerated compartment are exposed to tidal hyperinflation of the
      normally aerated compartment. MEASUREMENTS AND MAIN RESULTS: Pulmonary computed
      tomography at end-expiration and end-inspiration was obtained in 30 patients
      ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster
      analysis identified 20 patients in whom tidal inflation occurred largely in the
      normally aerated compartment (69.9 +/- 6.9%; "more protected"), and 10 patients
      in whom tidal inflation occurred largely within the hyperinflated compartments
      (63.0 +/- 12.7%; "less protected"). The nonaerated compartment was smaller and
      the normally aerated compartment was larger in the more protected patients than
      in the less protected patients (p = 0.01). Pulmonary cytokines were lower in the
      more protected patients than in the less protected patients (p < 0.05).
      Ventilator-free days were 7 +/- 8 and 1 +/- 2 d in the more protected and less
      protected patients, respectively (p = 0.01). Plateau pressure ranged between 25
      and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in
      the less protected patients (p = 0.006). CONCLUSIONS: Limiting tidal volume to 6
      ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be
      sufficient in patients characterized by a larger nonaerated compartment.

PMID- 17038661
TI  - Elevated morbidity and health care use in children with obstructive sleep apnea
      syndrome.
AB  - RATIONALE: Health care use, a reliable measure of morbidity, is noticeably higher
      1 yr before obstructive sleep apnea syndrome (OSAS) diagnosis in preschool
      children. It is not clear at what age OSAS-related morbidity becomes expressed.
      OBJECTIVE: To explore morbidity and health care use among children with OSAS
      starting from first year of life. METHODS: Case-control study, starting from the
      first year of life to date of OSAS diagnosis, among 156 patients (age range, 3-5
      yr) and their pair-matched healthy control subjects, by age, sex, primary care
      physician, and geographic location. MEASUREMENTS: Patients with OSAS underwent
      nocturnal polysomnography studies. Medical records during hospital visits were
      reviewed for diagnosis. Variables of health care use were obtained from
      computerized databases of Clalit Health Care Services, the largest health
      maintenance organization in Israel. MAIN RESULTS: From the first year of life to
      date of OSAS diagnosis, children with OSAS had 40% more (p = 0.048) hospital
      visits, 20% more repeated (two or more) visits (p < 0.0001), and higher
      consumption of antiinfective and respiratory system drugs (p < 0.0001). Referrals
      of children with OSAS to otolaryngology surgeons and pediatric pulmonologists
      were higher from Year 1 (p < 0.0001) to date of OSAS diagnosis, especially in
      Year 4 (odds ratio, 9.4; 95% confidence interval, 4.2-21.1). The 215% elevation
      (p < 0.0001) in health care use of the OSAS group was due mainly to higher
      occurrence of respiratory tract morbidity (p < 0.0001). CONCLUSIONS:
      Practitioners should be aware that starting in Year 1 until date of diagnosis,
      children with OSAS have higher health care use, mostly related to respiratory
      diseases.

PMID- 17038662
TI  - Unique uptake of acid-prepared mesoporous spheres by lung epithelial and
      mesothelioma cells.
AB  - Lung cancers, malignant mesotheliomas (MM), and fibrosis are devastating diseases
      with limited treatment strategies, in part due to poorly-effective drug delivery
      to affected areas of lung. We hypothesized that acid-prepared mesoporous spheres
      (APMS) (1-2 microm diameter, 40 A pore size) might be effective vehicles for
      pulmonary chemotherapeutic drug delivery. To assess this, APMS, chemically
      modified with different surface molecules (lipid, a linker having a terminal
      amine group, a thiol group, or tetraethylene glycol [TEG]), were evaluated for
      uptake and possible cytotoxic effects after in vitro administration to murine
      alveolar epithelial Type II (C10) and human mesothelioma (MM) cells and after
      intrapleural or intranasal administration to C57Bl/6 mice. APMS coated with TEG
      (APMS-TEG) were most efficiently taken up by C10 and MM cells. The mechanism of
      cell uptake was rapid, actin-dependent, and did not involve clathrin- or caveolae
      mediated mechanisms nor fusion of membrane-bound APMS with lysosomes. When
      injected intrapleurally in mice, APMS-TEG were taken up by both CD45-positive and
      -negative cells of the diaphragm, lung, and spleen, whereas APMS administered by
      the intranasal route were predominantly in lung epithelial cells and alveolar
      macrophages. After intrapleural or intranasal administration, APMS were
      nonimmunogenic and nontoxic as evaluated by differential cell counts and lactate
      dehydrogenase levels in bronchoalveolar and pleural lavage fluids. In the
      treatment of lung and pleural diseases, APMS-TEG may be useful tools to deliver
      chemotherapeutic drugs or molecular constructs.

PMID- 17038663
TI  - IL-2 and IL-18 attenuation of airway hyperresponsiveness requires STAT4, IFN
      gamma, and natural killer cells.
AB  - IL-18 is known to induce IFN-gamma production, which is enhanced when combined
      with IL-2. In the present study, we investigated whether the combination of
      exogenous IL-2 and IL-18 alters airway hyperresponsiveness (AHR) and airway
      inflammation. Sensitized mice exposed to ovalbumin (OVA) challenge developed AHR,
      inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and increases in
      levels of Th2 cytokines and goblet cell numbers. The combination of IL-2 and IL
      18, but neither alone, prevented these changes while increasing levels of IL-12
      and IFN-gamma. The combination of IL-2 and IL-18 was ineffective in IFN-gamma
      deficient and signal transducer and activator of transcription (STAT)4-deficient
      mice. Flow cytometry analysis showed significant increases in numbers of IFN
      gamma-positive natural killer (NK) cells in the lung after treatment with the
      combination therapy, and transfer of lung NK cells isolated from sensitized and
      challenged mice treated with the combination significantly suppressed AHR and BAL
      eosinophilia. These data demonstrate that the combination of IL-2 and IL-18
      prevents AHR and airway inflammation, likely through IL-12-mediated induction of
      IFN-gamma production in NK cells.

PMID- 17038665
TI  - Fibroblast growth factor 2 modulates transforming growth factor beta signaling in
      mouse embryonic fibroblasts and human ESCs (hESCs) to support hESC self-renewal.
AB  - Fibroblast growth factor 2 (FGF2) is known to promote self-renewal of human
      embryonic stem cells (hESCs). In addition, it has been shown that transforming
      growth factor beta (TGFbeta) signaling is crucial in that the
      TGFbeta/Activin/Nodal branch of the pathway needs to be activated and the bone
      morphogenic protein (BMP)/GDF branch repressed to prevent differentiation. This
      holds particularly true for Serum Replacement-based medium containing BMP-like
      activity. We have reinvestigated a widely used protocol for conditioning hESC
      medium with mouse embryonic fibroblasts (MEFs). We show that FGF2 acts on MEFs to
      release supportive factors and reduce differentiation-inducing activity. FGF2
      stimulation experiments with supportive and nonsupportive MEFs followed by genome
      wide expression profiling revealed that FGF2 regulates the expression of key
      members of the TGFbeta pathway, with Inhba, Tgfb1, Grem1, and Bmp4 being the most
      likely candidates orchestrating the above activities. In addition, restimulation
      experiments in hESCs combined with global expression analysis revealed downstream
      targets of FGF2 signaling in these cells. Among these were the same factors
      previously identified in MEFs, thus suggesting that FGF2, at least in part,
      promotes self-renewal of hESCs by modulating the expression of TGFbeta ligands,
      which, in turn, act on hESCs in a concerted and autocrine manner.

PMID- 17038664
TI  - Role of protein cavities on unfolding volume change and on internal dynamics
      under pressure.
AB  - The effects of two single point cavity forming mutations, F110S and I7S, on the
      unfolding volume change (DeltaV(0)) of azurin from Pseudomonas aeruginosa and on
      the internal dynamics of the protein fold under pressure were probed by the
      fluorescence and phosphorescence emission of Trp-48, deeply buried in the compact
      hydrophobic core of the macromolecule. Pressure-induced unfolding, monitored by
      the shift of the center of mass of the fluorescence spectrum, showed that
      DeltaV(0) is in the range of 60-70 mL/mol, not significantly different between
      cavity mutants and compact azurin species such as the wild-type and the mutant
      C3A/C26A, in which the superficial disulphide has been removed. The lack of extra
      volume in F110S and I7S proves that the engineered cavities, 40 A(3) in I7S and
      100 A(3) in F110S, are filled with water molecules. Changes in flexibility of the
      protein matrix around the chromophore were monitored by the intrinsic
      phosphorescence lifetime (tau(0)). The application of pressure in the
      predenaturation range initially decreases the internal flexibility of azurin, the
      trend eventually reverting on approaching unfolding. The main difference between
      compact folds, wild-type and C3A/C26A, and cavity mutants is that the inversion
      point is powered from approximately 3 kbar to 1.5 kbar for F110S and <0.1 kbar
      for I7S, meaning that in the latter species pressure-induced internal hydration
      dominates very early over any compaction of the globular fold resulting from the
      reduction of internal free volume. The similar response between wild-type and the
      significantly less-stable C3A/C26A mutant suggests that thermodynamic stability
      per se is not the dominant factor regulating pressure-induced internal hydration
      of proteins.

PMID- 17038666
TI  - Impaired downregulation following erythropoietin receptor activation in non-small
      cell lung carcinoma.
AB  - Recent evidence confirms the presence of erythropoietin receptors on a variety of
      cancer cells. This has raised concerns about the use of erythropoiesis
      stimulating agents in the treatment of cancer-related anemia. Having previously
      identified expression of functional erythropoietin receptors in a non-small cell
      lung carcinoma cell line, H838, which activated key signaling pathways in
      response to erythropoietin stimulation, we now demonstrate impaired
      downregulation of the erythropoietin receptor in these tumor cells. The
      erythropoietin receptor is not ubiquitinated following erythropoietin stimulation
      in this cancer cell line, and there is no turnover of the receptor in either
      unstimulated or stimulated cells. Compounding this blunted response is impaired
      SOCS3 induction downstream of erythropoietin stimulation and an extremely delayed
      SOCS1 response. If this finding in non-small cell lung carcinoma is a widespread
      phenomenon, then impaired erythropoietin receptor downregulation and degradation
      in tumor cells has clinical implications for those patients receiving
      erythropoiesis-stimulating agents for cancer-related anemia.

PMID- 17038667
TI  - Identification of candidate murine esophageal stem cells using a combination of
      cell kinetic studies and cell surface markers.
AB  - The identification and characterization of esophageal stem cells are critical to
      our understanding of the biology of the esophageal epithelium in health and
      disease. However, the proliferative compartment within the mouse esophageal
      epithelium remains poorly characterized. Here, we report that the basal cells of
      the mouse esophagus can be separated into three phenotypically and functionally
      distinct subpopulations based on the expression of alpha(6) integrin and
      transferrin receptor (CD71). Cells that express high levels of alpha(6) integrin
      and low levels of CD71, termed alpha(6)(bri)CD71(dim), are a minor subpopulation
      of small and undifferentiated cells that are enriched for label-retaining cells
      and thus represent a putative esophageal stem cell population. Conversely, cells
      expressing high levels of both alpha(6) integrin and CD71
      (alpha(6)(bri)CD71(bri)), the majority of basal esophageal cells, are enriched
      for actively cycling cells and therefore represent a transit-amplifying
      population. Kinetic analyses revealed that a third cell population, which is
      alpha(6) integrin-dim and CD71-bright (alpha(6)(dim)), is destined to leave the
      basal layer and differentiate.

PMID- 17038668
TI  - Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic
      neurons from human embryonic stem cells using the bone morphogenic protein
      antagonist noggin.
AB  - It is currently not known whether dopamine (DA) neurons derived from human
      embryonic stem cells (hESCs) can survive in vivo and alleviate symptoms in models
      of Parkinson disease (PD). Here, we report the use of Noggin (a bone morphogenic
      protein antagonist) to induce neuroectodermal cell development and increase the
      yield of DA neurons from hESCs. A combination of stromal-derived inducing
      activity and Noggin markedly enhanced the generation of neuroepithelial
      progenitors that could give rise to DA neurons. In addition, Noggin diminished
      the occurrence of a fibroblast-like Nestin-positive precursor population that
      differentiated into myocytes. After transplantation of differentiated hESCs to a
      rodent model of PD, some grafts contained human midbrain-like DA neurons. This
      protocol demonstrates hESC derivation and survival of human DA neurons
      appropriate for cell therapy in PD.

PMID- 17038669
TI  - Multipotent cell fate of neural crest-like cells derived from embryonic stem
      cells.
AB  - Neural crest cells migrate throughout the embryo and differentiate into diverse
      derivatives: the peripheral neurons, cranial mesenchymal cells, and melanocytes.
      Because the neural crest cells have critical roles in organogenesis, detailed
      elucidation of neural crest cell differentiation is important in developmental
      biology. We recently reported that melanocytes could be induced from mouse ESCs.
      Here, we improved the culture system and showed the existence of neural crest
      like precursors. The addition of retinoic acid to the culture medium reduced the
      hematopoiesis and promoted the expression of the neural crest marker genes. The
      colonies formed contained neural crest cell derivatives: neurons and glial cells,
      together with melanocytes. This suggested that neural crest-like cells assuming
      multiple cell fates had been generated in these present cultures. To isolate the
      neural crest-like cells, we analyzed the expression of c-Kit, a cell-surface
      protein expressed in the early stage of neural crest cells in vivo. The c-Kit
      positive (c-Kit(+)) cells appeared as early as day 9 of the culture period and
      expressed the transcriptional factors Sox10 and Snail, which are expressed in
      neural crest cells. When the c-Kit(+) cells were separated from the cultures and
      recultured, they frequently formed colonies containing neurons, glial cells, and
      melanocytes. Even a single c-Kit(+) cell formed colonies that contained these
      three cell types, confirming their multipotential cell fate. The c-Kit(+) cells
      were also capable of migrating along neural crest migratory pathways in vivo.
      These results indicate that the c-Kit(+) cells isolated from melanocyte
      differentiating cultures of ESCs are closely related to neural crest cells.

PMID- 17038670
TI  - Distinct population of hair cell progenitors can be isolated from the postnatal
      mouse cochlea using side population analysis.
AB  - In mammals, the permanence of hearing loss is due mostly to the incapacity of the
      cochlea to replace lost mechano-receptor cells (i.e., hair cells [HCs]). The
      generation of new HCs from a renewable source of progenitors is a principal
      requirement for developing a cell therapy within this sensory organ. A subset of
      stem cells, termed side population (SP), has been identified in several tissues
      of mammals. The ATP-binding cassette transporter Abcg2/Bcrp1 contributes to the
      specification of the SP phenotype and is proposed as a universal marker for
      stem/progenitor cells. A defining character of these SP cells is a high efflux
      capacity for Hoechst dye. Here, we demonstrate that Abcg2 transporter is
      expressed with two other stem/progenitor cell markers (i.e., Nestin and Musashi1)
      in distinct and overlapping domains of the supporting cells within the postnatal
      cochlea. We have developed and describe a fluorescence-activated cell sorting
      (FACS) technique that enables the purification of a discrete subpopulation of SP
      supporting cells from the early postnatal mouse cochlea based on their ability to
      exclude Hoechst dye. These FACS-isolated cells can divide and express markers of
      stem/progenitor cells such as Abcg2, a determinant of the SP phenotype, and
      Musashi1, a neural stem/progenitor cell marker. These markers can differentiate
      cells expressing markers of HCs and supporting cells in vitro. Our observation
      that these SP cells are capable of differentiating into HC-like cells implies a
      possible use for such cells (i.e., the replacement of lost auditory HCs within
      damaged cochlea).

PMID- 17038672
TI  - Generation and characterization of rabbit embryonic stem cells.
AB  - We described the derivation of four stable pluripotent rabbit embryonic stem cell
      (ESC) lines, one (RF) from blastocysts fertilized in vivo and cultured in vitro
      and three (RP01, RP02, and RP03) from parthenogenetic blastocysts. These ESC
      lines have been cultivated for extended periods (RF >1 year, RP01 >8 months, RP02
      >8 months, and RP03 >6 months) in vitro while maintaining expression of
      pluripotent ESC markers and a normal XY or XX karyotype. The ESCs from all lines
      expressed alkaline phosphatase, transcription factor Oct-4, stage-specific
      embryonic antigens (SSEA-1, SSEA-3, and SSEA-4), and the tumor-related antigens
      (TRA-1-60 and TRA-1-81). Similar to human and mouse ESCs, rabbit ESCs expressed
      pluripotency (Oct-4, Nanog, SOX2, and UTF-1) and signaling pathway genes
      (fibroblast growth factor, WNT, and transforming growth factor pathway).
      Morphologically, rabbit ESCs resembled primate ESCs, whereas their proliferation
      characteristics were more like those seen in mouse ESCs. Rabbit ESCs were induced
      to differentiate into many cell types in vitro and formed teratomas with
      derivatives of the three major germ layers in vivo when injected into severe
      combined immunodeficient mice. Our results showed that pluripotent, stable ESC
      lines could be derived from fertilized and parthenote-derived rabbit embryos.

PMID- 17038671
TI  - Microarray analyses support a role for Nurr1 in resistance to oxidative stress
      and neuronal differentiation in neural stem cells.
AB  - Nurr1 is an orphan nuclear receptor required for the development of midbrain
      dopaminergic neurons. To better understand the molecular consequences of Nurr1
      expression, we compared the transcriptomes of two independent control and Nurr1
      expressing NSC lines using Affymetrix cDNA microarrays. These data reveal the
      regulation of genes involved in promoting cell survival (trophic/growth factors
      and stress response genes) and in preventing cell death (decreased caspase-3 and
      caspase-11 expression). We found that conditioned medium from Nurr1-expressing
      NSC lines enhanced the survival of midbrain dopaminergic neurons in primary
      cultures and that Nurr1-expressing NSC lines themselves were more resistant to
      oxidative stress. These findings are accompanied by a dynamic pattern of gene
      regulation that is consistent with a role for Nurr1 in promoting both the
      acquisition of brain-region-specific identity (Engrailed-1) and neuronal
      differentiation (tubulin beta III). Interestingly, our gene expression profiles
      suggested that tenascin-C was regulated by Nurr1 in developing dopaminergic
      neurons. This was further confirmed in vitro and in Nurr1 knockout mice where low
      levels of tenascin-C mRNA were observed. Analysis of tenascin-C-null mice
      revealed an increase in the number of Nurr1(+) cells that become tyrosine
      hydroxylase-positive (TH(+)) dopaminergic neurons at embryonic day 11.5,
      suggesting that tenascin-C normally delays the acquisition of TH by Nurr1(+)
      precursors. Thus, our results confirm the presence of both secreted and cell
      intrinsic survival signals modulated by Nurr1 and suggest that Nurr1 is a key
      regulator of both survival and dopaminergic differentiation.

PMID- 17038673
TI  - Molecular analysis of LEFTY-expressing cells in early human embryoid bodies.
AB  - Human ESCs (HESCs) are self-renewing pluripotent cell lines that are derived from
      the inner cell mass of blastocyst-stage embryos. These cells can produce
      terminally differentiated cells representing the three embryonic germ layers. We
      thus hypothesized that during the course of in vitro differentiation of HESCs,
      progenitor-like cells are transiently formed. We demonstrated that LEFTY
      proteins, which are known to play a major role during mouse gastrulation, are
      transiently expressed during HESC differentiation. Moreover, LEFTY proteins
      seemed to be exclusively expressed by a certain population of cells in the early
      human embryoid bodies that does not overlap with the population expressing the
      ESC marker OCT4. We also showed that LEFTY expression is regulated at the
      cellular transcription level by molecular labeling of LEFTY-positive cells. A DNA
      microarray analysis of LEFTY-overexpressing cells revealed a signature of cell
      surface markers such as CADHERIN 2 and 11. Expression of LEFTY controlled by
      NODAL appears to have a substantial role in mesodermal origin cell population
      establishment, since inhibition of NODAL activity downregulated expression not
      only of LEFTY A and LEFTY B but also of BRACHYURY, an early mesodermal marker. In
      addition, other mesodermal lineage-related genes were downregulated, and this was
      accompanied by an upregulation in ectoderm-related genes. We propose that during
      the initial step of HESC differentiation, mesoderm progenitor-like cells appear
      via activation of the NODAL pathway. Our analysis suggests that in vitro
      differentiation of HESCs can model early events in human development.

PMID- 17038674
TI  - Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like
      organization of human embryonic stem cell-derived endothelium in vitro.
AB  - The molecular mechanisms that regulate human blood vessel formation during early
      development are largely unknown. Here we used human ESCs (hESCs) as an in vitro
      model to explore early human vasculogenesis. We demonstrated that stromal cell
      derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived
      embryonic endothelial differentiation. Human ESC-derived embryonic endothelial
      cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular
      network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary
      like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway
      by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth
      from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical
      role in regulating initial vessel formation, and may function as a morphogen
      during human embryonic vascular development.

PMID- 17038675
TI  - Sarcoma derived from cultured mesenchymal stem cells.
AB  - To study the biodistribution of MSCs, we labeled adult murine C57BL/6 MSCs with
      firefly luciferase and DsRed2 fluorescent protein using nonviral Sleeping Beauty
      transposons and coinfused labeled MSCs with bone marrow into irradiated
      allogeneic recipients. Using in vivo whole-body imaging, luciferase signals were
      shown to be increased between weeks 3 and 12. Unexpectedly, some mice with the
      highest luciferase signals died and all surviving mice developed foci of sarcoma
      in their lungs. Two mice also developed sarcomas in their extremities. Common
      cytogenetic abnormalities were identified in tumor cells isolated from different
      animals. Original MSC cultures not labeled with transposons, as well as
      independently isolated cultured MSCs, were found to be cytogenetically abnormal.
      Moreover, primary MSCs derived from the bone marrow of both BALB/c and C57BL/6
      mice showed cytogenetic aberrations after several passages in vitro, showing that
      transformation was not a strain-specific nor rare event. Clonal evolution was
      observed in vivo, suggesting that the critical transformation event(s) occurred
      before infusion. Mapping of the transposition insertion sites did not identify an
      obvious transposon-related genetic abnormality, and p53 was not overexpressed.
      Infusion of MSC-derived sarcoma cells resulted in malignant lesions in secondary
      recipients. This new sarcoma cell line, S1, is unique in having a cytogenetic
      profile similar to human sarcoma and contains bioluminescent and fluorescent
      genes, making it useful for investigations of cellular biodistribution and tumor
      response to therapy in vivo. More importantly, our study indicates that sarcoma
      can evolve from MSC cultures.

PMID- 17038676
TI  - Evidence for transmission of Plasmodium vivax among a duffy antigen negative
      population in Western Kenya.
AB  - We present evidence that a parasite with characteristics of Plasmodium vivax is
      being transmitted among Duffy blood group-negative inhabitants of Kenya. Thirty
      two of 4,901 Anopheles gambiae and An. funestus (0.65%) collected in Nyanza
      Province were ELISA positive for the P. vivax circumsporozoite protein VK 247.
      All positives were found late in the rainy season, when An. funestus
      predominated, and disproportionately many were found at a single village. A P.
      vivax specific sequence of the SSU rRNA gene was amplified from three of six
      ELISA-positive mosquitoes. Erythrocytes from 31 children, including 9
      microscopically diagnosed as infected with P. vivax, were negative by flow
      cytometry for the Fy3 or Fy6 epitopes, which indicate Duffy blood group
      expression. A DNA fragment specific for the C terminus of the gene for P. vivax
      merozoite surface protein 1 (MSP-1) was amplified from the blood of four of these
      children and subsequently sequenced from two.

PMID- 17038677
TI  - Antibodies to Plasmodium vivax apical membrane antigen 1: persistence and
      correlation with malaria transmission intensity.
AB  - The antibody responses to the apical membrane antigen 1 of the Plasmodium vivax
      (PvAMA-1) were investigated in subjects living in areas of Brazil with different
      levels of malaria transmission. The prevalence and the levels of IgG to PvAMA-1
      increased with the time of exposure. The frequency of a positive response and the
      mean IgG level were higher in areas where malaria prevalence was more intense,
      especially among non-infected subjects exposed to moderate transmission over a
      period of 20 years. The proportions and levels of IgG1and IgG3 isotypes were
      significantly higher among those subjects with long-term exposure. Antibodies,
      mainly IgG1, to PvAMA-1 persisted for seven years among subjects briefly exposed
      to malaria in an outbreak outside the Brazilian malaria-endemic area. These data
      show the highly immunogenic properties of PvAMA-1 and emphasize its possible use
      as a malaria vaccine candidate.

PMID- 17038679
TI  - Placental malaria in women with South-East Asian ovalocytosis.
AB  - Malaria during pregnancy, which is characterized by the accumulation of infected
      erythrocytes in the placenta, often has severe consequences for the mother and
      newborn. We assessed the effect of the genetic trait South-East Asian
      ovalocytosis (SAO) on placental malaria in women from Papua New Guinea. In
      children, this trait confers protection against cerebral malaria, but not against
      mild malaria disease, malaria parasitemia, or severe malaria anemia. Using a case
      control approach, we found that SAO women suffer from placental malaria, and SAO
      infected erythrocytes can sequester in the placenta, but heavy placental
      infections tended to be less common in SAO than in control pregnant women.
      Reduced prevalence and severity of placental infection associated with SAO were
      observed only for primigravid women, who are the group at highest risk of
      suffering from severe manifestations of placental malaria. Furthermore, we found
      that the prevalence of the SAO trait was lower among pregnant women than among
      non-pregnant controls.

PMID- 17038678
TI  - Changing patterns of Plasmodium blood-stage infections in the Wosera region of
      Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis.
AB  - In Papua New Guinea (PNG), complex patterns of malaria commonly include single
      and mixed infections of Plasmodium falciparum, P. vivax, P. malariae, and P.
      ovale. Here, we assess recent epidemiologic characteristics of Plasmodium blood
      stage infections in the Wosera region through four cross-sectional surveys
      (August 2001 to June 2003). Whereas previous studies performed here have relied
      on blood smear/light microscopy (LM) for diagnosing Plasmodium species
      infections, we introduce a newly developed, post-polymerase chain reaction (PCR),
      semi-quantitative, ligase detection reaction-fluorescent microsphere assay (LDR
      FMA). A direct comparison of the two methods for > 1,100 samples showed that
      diagnosis was concordant for > 80% of the analyses performed for P. falciparum
      (PF), P. vivax (PV), and P. malariae (PM). Greater sensitivity of the LDR-FMA
      accounted for 75% of the discordance between diagnoses. Based on LM, the
      prevalence of blood-stage PF, PV, and PM infections was found to be markedly
      reduced compared with an early 1990s survey. In addition, there were significant
      shifts in age distribution of infections, with PV becoming the most common
      parasite in children < 4 years of age. Consistent with previous studies,
      prevalence of all Plasmodium species infections increased significantly in
      samples analyzed by the PCR-based LDR-FMA. This increase was most pronounced for
      PM, PO, and mixed infections and in adolescent (10-19 years) and adult age
      groups, suggesting that LM may lead to under-reported prevalence of less common
      Plasmodium species, infection complexity, and a skewed distribution of infections
      towards younger age groups. This study shows that the application of LDR-FMA
      diagnosis in large epidemiologic studies or malaria control interventions is
      feasible and may contribute novel insights regarding the epidemiology of malaria.

PMID- 17038680
TI  - Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium
      vivax malaria in Colombia.
AB  - Plasmodium vivax malaria is an important cause of morbidity in Central and South
      America. In Colombia, this is the most prevalent malaria infection, representing
      75% of the reported cases. To define the efficacy of the chloroquine and
      primaquine regimen to eliminate hypnozoites and prevent relapses, we conducted a
      random controlled clinical trial of three primaquine regimens in an open-label
      study. We evaluated the anti-relapse efficacy of total primaquine doses of 45,
      105, and 210 mg administered at a dosage of 15 mg/day in 210 adults with P. vivax
      infection from the northwestern region of Colombia. Cure rates for blood-stage P.
      vivax malaria by day 28 of follow-up were 100% in all groups. Post-treatment
      reappearance of parasitemia during the six months of follow-up was 45%, 36.6% and
      17.6%, respectively, for each group. When compared with other groups,
      administration of 210 mg was a significant protection factor for reappearance of
      parasitemia in a malaria-endemic area.

PMID- 17038681
TI  - Experimental infection of the neotropical malaria vector Anopheles darlingi by
      human patient-derived Plasmodium vivax in the Peruvian Amazon.
AB  - Malaria transmission from humans to mosquitoes is modulated by human host immune
      factors. Understanding mechanisms by which the human host response may impair
      parasite infectivity for mosquitoes has direct implications for the development
      of transmission-blocking vaccines. We hypothesized that despite a low
      transmission intensity of malaria in the Peruvian Amazon region of Iquitos,
      transmission-blocking immunity against Plasmodium vivax might be common, given an
      unexpectedly high proportion of asymptomatic parasitemic individuals in this
      region. To test this hypothesis, the ability of symptomatic P. vivax malaria
      patients to experimentally infect wild-caught outbred Anopheles darlingi
      mosquitoes was tested using the indirect membrane feeding technique. Only half
      (52/102) of P. vivax parasitemic patients successfully infected mosquitoes.
      Transmitters were more likely to have gametocytes (OR 6.35, P = 0.003), high
      parasitemia (OR 3.79, P = 0.024), and, in terms of basic clinical parameters, a
      slower pulse rate (mean +/- SD: 82.3 +/- 12.3 versus 88.7 +/- 13.5, P = 0.016)
      than non-transmitters. Log(10) gametocytemia and log(10) real-time reverse
      transcriptase Pvs25 PCR quantifying gametocytes were significantly and positively
      correlated with oocyst counts (correlation coefficient 0.505, R2 = 0.26, P =
      0.001). These experiments are the first to establish a system of determining
      transmission patterns in experimental infection of outbred natural neotropical
      malaria vectors in the Amazon region. Patients with P. vivax inefficiently infect
      outbred An. darlingi mosquitoes, raising the possibility that some degree of
      naturally occurring transmission-blocking immunity is present on a population
      basis in the Peruvian Amazon, an area of low intensity of malaria transmission.

PMID- 17038682
TI  - Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical
      regions and susceptibility to antifolate drugs.
AB  - The increasing use of sulfadoxine-pyrimethamine (SP) for the treatment of
      chloroquine-resistant Plasmodium falciparum has resulted in increased reports of
      SP resistance of P. falciparum worldwide. Selection of SP-resistant Plasmodium
      vivax in areas where P. falciparum and P. vivax co-exist is not entirely clear.
      We examined the prevalence and extent of point mutations in pvdhfr and pvdhps in
      70 P. vivax isolates from China, East Timor, Papua New Guinea (PNG), Philippines,
      Vanuatu, and Vietnam. Mutations in seven codon positions were found in pvdhfr,
      with the majority of isolates having double mutations (S58R/S117N). The greatest
      range of mutations was observed in the PNG and Vanuatu isolates, ranging from
      single to quadruple mutations (F57L/S58R/T61M/S117T). Single mutations in pvdhps
      were observed only in parasites with mutations in corresponding pvdhfr. Parasites
      with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and
      cycloguanil comparable to that previously reported, but were susceptible to
      WR99210.

PMID- 17038683
TI  - Burden of malaria at community level in children less than 5 years of age in
      Togo.
AB  - A community-based baseline cross-sectional survey was conducted in three
      districts in Togo in September 2004 as part of a multidisciplinary evaluation of
      the impact of the Togo National Integrated Child Health Campaign. During this
      campaign, long-lasting-insecticide-treated bed nets (LLITNs) were distributed to
      households with children between 9 months and 5 years of age throughout the
      country in December 2004. The pre-intervention survey provided baseline malaria
      and anemia prevalence in children < 5 years of age during peak malaria
      transmission. Of 2,532 enrolled children from 1,740 households, 62.2%
      (1,352/2,172) were parasitemic and 84.4% (2,129/2,524) were anemic (hemoglobin <
      11 g/dL). Moderate-to-severe anemia (< 8.0 g/dL) was found in 21.7% (543/2,524),
      with a peak prevalence in children 6-17 months of age and was strongly correlated
      with parasitemia (OR = 2.3, 95% CI: 1.8-2.5). Net ownership (mainly untreated)
      was 225/2,532 (8.9%). Subsequent nation-wide introduction of LLITNs and the
      introduction of artemisinin-based combination therapy have the potential to
      markedly reduce this burden of malaria.

PMID- 17038684
TI  - A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus
      artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum
      malaria in Mali.
AB  - The choice of artemisinin-based combination that is being adopted for malaria
      treatment in sub-Saharan Africa may depend on several factors, including cost,
      efficacy, side effects, and simplicity of administration. We tested the
      hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious
      as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium
      falciparum malaria. The study was carried out during two transmission seasons
      (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with
      uncomplicated P. falciparum malaria were randomly assigned to receive artesunate
      sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy
      was assessed using the World Health Organization 28-day protocol. A total of 606
      (303 in each arm) patients were enrolled. The cure rate was higher for artesunate
      sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus
      89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates
      were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred.
      Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective
      against P. falciparum malaria. It showed an additional benefit of preventing new
      infections.

PMID- 17038685
TI  - In vitro activity of artemisone compared with artesunate against Plasmodium
      falciparum.
AB  - Artemisinins show the potential for neurotoxicity in preclinical studies.
      Artemisone is a leading candidate of second-generation semi-synthetic artemisinin
      derivatives for antimalarial therapy devoid of neurotoxicity. Artemisone showed 3
      5-fold higher in vitro activity (50% effective concentration (EC50) = 0.14
      nmol/L, EC90 = 2.55 nmol/L) than artesunate against fresh Plasmodium falciparum
      isolates from Gabon and a high-activity correlation indicates a shared drug
      target.

PMID- 17038686
TI  - Use of area under the curve to characterize transmission potential after
      antimalarial treatment.
AB  - To evaluate transmission potential of Plasmodium falciparum, we use the area
      under the curve (AUC) of gametocyte levels after treatment as an approach to
      combine their duration and magnitude. Analysis of determinants of AUC was based
      on two main exposures: parasite clearance time (PCT) and presence of
      dihydrofolate reductase and dihydropteroate synthase mutations associated with
      sulfadoxine-pyrimethamine (SP) resistance in vitro. Exposures were determined
      based on the first three days after treatment with SP of 96 individuals who had
      malaria, cleared parasitemia by days 1-3, and were followed-up for 21 days. Using
      regression methods, we characterized both the heterogeneity of the presence of
      gametocytes (AUC > 0) and the magnitude of the AUC among those with an AUC > 0. A
      PCT of two or three days was associated with a substantial and highly significant
      odds ratio for presence of gametocytes. Among those who developed gametocytes, if
      their clearance time was 3 days or if they had any mutations (1 or 2) the
      magnitude of gametocytemia was > or = 3-fold. Methods presented are applicable to
      both observational studies and clinical trials assessing the effect of therapies
      on transmission potential.

PMID- 17038687
TI  - Therapeutic efficacy of quinine plus sulfadoxine-pyremethamine for the treatment
      of uncomplicated falciparum malaria in Bangladesh.
AB  - In terms of drug resistance Bangladesh acts as an important gateway to the Indian
      Subcontinent. However, little is known about the current status of drug
      resistance in this country. The aim of this study was therefore to determine the
      therapeutic efficacy as well as in vitro drug sensitivity of quinine for 3 days
      plus a single dose of sulfadoxine/pyrimethamine (Q3F), an affordable alternative
      to the previously used chloroquine, for the treatment of uncomplicated falciparum
      malaria. Sixty-three patients were enrolled in the study; the overall cure rate
      in a 42-day follow-up after PCR adjustment was 87.3% (95% CI: 77.6-94.1). One
      patient was classified as early treatment failure (1.7%, 95% CI: 0.0-8.9%); 6
      patients (10%; 95% CI: 3.8-20.5%) had late treatment failures within a median
      time of 27 days. HRP2 in vitro drug sensitivity tests were performed on all
      samples. Significantly higher (P = 0.008) in vitro IC(50)s for pyrimethamine in
      treatment failures reflect the somewhat compromised drug sensitivity to this
      drug. These data suggest that the combination of 3 days of quinine with a single
      dose of sulfadoxine/pyrimethamine is an interesting and affordable alternative as
      long as or whenever ACT is not available.

PMID- 17038688
TI  - Successful integration of insecticide-treated bed net distribution with mass drug
      administration in Central Nigeria.
AB  - In Africa anopheline mosquitoes transmit malaria and lymphatic filariasis (LF);
      insecticide-treated bed nets significantly reduce transmission of both.
      Insecticide-treated bed net provision to children under 5 (U5) and pregnant women
      (PW) is a major goal of malaria control initiatives, but use in Africa remains
      low because of cost and logistics. We therefore integrated insecticide-treated
      bed net distribution with the 2004 LF/onchocerciasis mass drug administration
      (MDA) program in Central Nigeria. Community volunteers distributed 38,600
      insecticide-treated bed nets, while simultaneously treating 150,800 persons with
      ivermectin/albendazole (compared with 135,600 in 2003). This was subsequently
      assessed with a 30-cluster survey. Among surveyed households containing U5/PW,
      80% (95% CI, 72-87%) owned > or = 1 insecticide-treated bed net, a 9-fold
      increase from 2003. This first linkage of insecticide-treated bed net
      distribution with mass drug administration resulted in substantial improvement in
      insecticide-treated bed net ownership and usage, without adversely affecting mass
      drug administration coverage. Such integration allowed two programs to share
      resources while realizing mutual benefit, and is one model for rapidly improving
      insecticide-treated bed net coverage objectives.

PMID- 17038689
TI  - Multilocus enzyme electrophoresis supports speciation within the Anopheles nili
      group of malaria vectors in Cameroon.
AB  - Multilocus enzyme analysis of the genetic variability and population structure
      was conducted among three malaria vector species of the Anopheles nili group in
      Cameroon: An. nili, An. carnevalei, and the recently described An. ovengensis. We
      detected species-specific alleles and large differences in shared allele
      frequencies at six of nine loci (e.g., PGM, GOT1, IDH1, IDH2, PGI, and alpha
      GPD). This non-random distribution of alleles leads to high and significant
      values of differentiation indexes (0.569 < Fst < 0.874, P < 10(-4)). These
      results fully agree with standard morphologic descriptions, and therefore provide
      further support for recent taxonomic classification within the An. nili group.

PMID- 17038690
TI  - Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax
      with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE).
AB  - Australian mosquitoes from which Japanese encephalitis virus (JEV) has been
      recovered (Culex annulirostris, Culex gelidus, and Aedes vigilax) were assessed
      for their ability to be infected with the ChimeriVax-JE vaccine, with yellow
      fever vaccine virus 17D (YF 17D) from which the backbone of ChimeriVax-JE vaccine
      is derived and with JEV-Nakayama. None of the mosquitoes became infected after
      being fed orally with 6.1 log(10) plaque-forming units (PFU)/mL of ChimeriVax-JE
      vaccine, which is greater than the peak viremia in vaccinees (mean peak viremia =
      4.8 PFU/mL, range = 0-30 PFU/mL of 0.9 days mean duration, range = 0-11 days).
      Some members of all three species of mosquito became infected when fed on JEV
      Nakayama, but only Ae. vigilax was infected when fed on YF 17D. The results
      suggest that none of these three species of mosquito are likely to set up
      secondary cycles of transmission of ChimeriVax-JE in Australia after feeding on a
      viremic vaccinee.

PMID- 17038691
TI  - Natural Anaplasma phagocytophilum infection of ticks and rodents from a forest
      area of Jilin Province, China.
AB  - Polymerase chain reaction integrated with sequence analysis was carried out to
      investigate the natural Anaplasma phagocytophilum infection in ticks and rodents
      from a forest area of Jilin Province, China. Four (4.0%) of 100 Ixodes
      persulcatus and 2 (0.7%) of 286 Dermacentor silvarum ticks collected by flagging
      vegetation were positive. Nine (8.8%) of 102 rodents were infected, as well as 2
      (2.8%) of 71 I. persulcatus parasitizing on 25 rodents. The nucleotide sequences
      of 1442-bp A. phagocytophilum 16S rRNA gene amplified from rodents and ticks were
      identical to each other and to that previously reported in Heilongjiang Province
      of China (GenBank accession no. AF205140), but different from those of other
      countries. The sequences of 357-bp partial citrate synthase gene from the above
      specimens were homologic, and varied from known A. phagocytophilum agents. These
      findings add new information on the ecologic features of A. phagocytophilum and
      indicate the threat of anaplasmosis in the area.

PMID- 17038692
TI  - Spatial patterns of Lyme disease risk in California based on disease incidence
      data and modeling of vector-tick exposure.
AB  - Ixodes pacificus, particularly the nymphal life stage, is the primary vector to
      humans of the Lyme disease agent Borrelia burgdorferi in California. During 2004,
      we collected I. pacificus nymphs from 78 woodland sites in ecologically diverse
      Mendocino County, which has a moderately high incidence of Lyme disease. Within
      this county, nymphal density was elevated in forested areas with a growing degree
      day range of 2,600-3,000 (10 degrees C base). Using a geographic information
      systems approach, we identified all areas in California sharing these
      environmental characteristics and thus projected to pose high acarologic risk of
      exposure to host-seeking nymphal ticks. Such areas were most commonly detected in
      the northwestern part of the state and along the Sierra Nevada foothills in the
      northeast, but the analysis also identified isolated areas with high acarologic
      risk in southern California. This mirrors the spatial distribution of endemic
      Lyme disease during 1993-2005; most cases occurred in counties to the northwest
      (58%) or northeast (26%), whereas fewer cases were reported from southern
      California (16%). Southern zip-codes from which Lyme disease cases had been
      reported were commonly located in close proximity to areas with high projected
      acarologic risk. Overall, Lyme disease incidence in zip code areas containing
      habitat with high projected acarologic risk was 10-fold higher than in zip code
      areas lacking such habitat and 27 times higher than for zip code areas without
      this habitat type within 50 km. A comparison of spatial Lyme disease incidence
      patterns based on county versus zip code units showed that calculating and
      displaying disease incidence at the zip code scale is a useful method to detect
      small, isolated areas with elevated disease risk that otherwise may go
      undetected.

PMID- 17038693
TI  - Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on
      pathogen acquisition.
AB  - We previously examined the physiological role of the anticoagulant salivary
      protein 14 (salp14) in adult Ixodes scapularis and showed that Salp14 played a
      role in tick feeding and engorgement. We now analyze whether the disruption of
      the salp14 family expression by RNA interference affects tick weight in naive
      nymph I. scapularis. Salp14 expression after dsRNA injection was significantly
      reduced, as shown by mRNA and protein analysis. However, nymph engorgement weight
      was not altered in salp9pac (salp14 paralog) dsRNA-injected ticks. We also
      determined Borrelia burgdorferi and Anaplasma phagocytophilum acquisition in I.
      scapularis nymphs that had reduced Salp14 expression. B. burgdorferi and A.
      phagocytophilum acquisition was not affected 72 hours after feeding. Our results
      suggest that different mechanisms govern nymph and adult feeding in I.
      scapularis.

PMID- 17038694
TI  - Scabies mite inactivated serine protease paralogues are present both internally
      in the mite gut and externally in feces.
AB  - The scabies mite, Sarcoptes scabiei, is the causative agent of scabies, a disease
      that is common among disadvantaged populations and facilitates streptococcal
      infections with serious sequelae. Previously, we encountered large families of
      genes encoding paralogues of house dust mite protease allergens with their
      catalytic sites inactivated by mutation (scabies mite inactivated protease
      paralogues [SMIPPs]). We postulated that SMIPPs have evolved as an adaptation to
      the parasitic lifestyle of the scabies mite, functioning as competitive
      inhibitors of proteases involved in the host-parasite interaction. To propose
      testable hypotheses for their functions, it is essential to know their locations
      in the mite. Here we show by immunohistochemistry that SMIPPs exist in two
      compartments: 1) internal to the mite in the gut and 2) external to the mite
      after excretion from the gut in scybala (fecal pellets). SMIPPs may well function
      in both of these compartments to evade host proteases.

PMID- 17038695
TI  - West Nile virus quantification in feces of experimentally infected American and
      fish crows.
AB  - To better understand the potential environmental health risk presented by West
      Nile virus (WNV)-contaminated feces, we quantified the amount of WNV present in
      the feces of experimentally infected American crows (Corvus brachyrhynchos) and
      fish crows (Corvus ossifragus). Peak fecal titers ranged from 10(3.5) to 10(8.8)
      plaque-forming units (PFU)/g for 10 American crows and from 10(2.3) to 10(6.4)
      PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a
      potential for direct transmission of WNV. Thus, handlers of sick or dead birds
      should take appropriate precautions to avoid exposure to fecal material.

PMID- 17038696
TI  - West Nile virus infection of primary mouse neuronal and neuroglial cells: the
      role of astrocytes in chronic infection.
AB  - Primary cultures of embryonic murine neurons and newborn mouse astrocytes were
      inoculated with West Nile virus (WNV) strain NY385-99 to compare the pathogenesis
      of WNV infection in these types of CNS cells. Two different outcomes were
      observed. WNV infection in the neurons was rapidly progressive and destructive;
      within 5 days, all of the neurons were destroyed through apoptosis. WNV infection
      in the astrocytes evolved more slowly and did not seem to be highly lethal to the
      cells. The infected astrocytes continued to produce infectious virus (10(4.6)
      10(6.5) PFU/mL) for 114 days, in a permissive, persistent infection. During this
      period, WNV antigen could be shown in the cytoplasm of the infected astrocytes by
      immunocytochemical assay, transmission electron microscopy of ultrathin sections,
      and in the cell culture medium by complement fixation test. Our results with this
      in vitro experimental murine cell model indicate that astrocytes can develop
      chronic or persistent infection with WNV, suggesting that these cells may play a
      role in the maintenance of WNV in the CNS.

PMID- 17038697
TI  - Experimental infection of fox squirrels (Sciurus niger) with West Nile virus.
AB  - Tree squirrels (Sciurus spp.) have exhibited high seroprevalence rates,
      suggesting that they are commonly exposed to West Nile virus (WNV). Many
      characteristics of WNV infections in tree squirrels, such as the durations and
      levels of viremia, remain unknown. To better understand WNV infections in fox
      squirrels (S. niger), we subcutaneously inoculated fourteen fox squirrels with
      WNV. Peak viremias ranged from 10(4.00) plaque-forming units (PFU)/mL of serum on
      day 2 post-infection (DPI) to 10(4.98) PFU/mL on 3 DPI, although viremias varied
      between individuals. Oral secretions of some fox squirrels were positive for WNV
      viral RNA, occasionally to moderate levels (10(3.2) PFU equivalent/swab). WNV PFU
      equivalents in organs were low or undetectable on 12 DPI; gross and histologic
      lesions were rare. The viremia profiles of fox squirrels indicate that they could
      serve as amplifying hosts in nature. In addition, viral RNA in the oral cavity
      and feces indicate that this species could contribute to alternative WNV
      transmission in suburban communities.

PMID- 17038698
TI  - Pseudotyped viruses permit rapid detection of neutralizing antibodies in human
      and equine serum against Venezuelan equine encephalitis virus.
AB  - Virus envelope proteins are the primary targets of neutralizing antibody
      responses. The epitopes recognized differ sufficiently between virus subtypes and
      species to distinguish viruses and provide an important basis for disease
      diagnosis. Venezuelan equine encephalitis virus (VEEV) causes acute febrile
      illness in humans and has high mortality in equines. The most specific detection
      methods for serum antibodies use live virus in neutralization assays or in
      blocking enzyme linked immunosorbent assays. However, work with Venezuelan equine
      encephalitis virus requires biosafety level 3 containment and select agent
      security in the United States. We report two new assays for detection of
      Venezuelan equine encephalitis virus neutralizing antibody responses, based on
      virus pseudotypes. The first provides detection by marker gene expression after
      20 hours and is particularly suited for high-throughput screening; the second
      uses a new, rapid virus entry assay to give readouts within 1 hour. Both assays
      are safe, sensitive, and in general recapitulate neutralizing antibody titers
      obtained by conventional plaque reduction assays. Each is suitable as a rapid
      primary screen for detection of neutralizing antibodies against Venezuelan equine
      encephalitis virus.

PMID- 17038699
TI  - Molecular epidemiology of dengue type 3 virus in Brazil and Paraguay, 2002-2004.
AB  - We studied the molecular epidemiology of dengue virus type 3 (DENV-3) in Brazil
      and Paraguay by analyzing the 5' and 3' untranslated regions (5' and 3'UTRs) and
      the E protein gene of viruses isolated between 2002 and 2004. Both 5' and 3'UTRs
      were highly conserved. However, the 3'UTR of two isolates from Brazil contained
      eight nucleotide deletions compared with the remaining 26 viruses. Phylogenetic
      analyses suggested that DENV-3 was introduced into Brazil from the Caribbean
      Islands at least twice and into Paraguay from Brazil at least three times.

PMID- 17038700
TI  - Exposure to human respiratory viruses among urban performing monkeys in
      Indonesia.
AB  - Performing monkeys, a common phenomena in Asia, occupy a unique urban niche that
      comprises a number of factors influencing the likelihood of cross-species
      transmission of pathogens. Here we present the first documented evidence of
      exposure to measles, rubella, and parainfluenza in a population of performing
      monkeys. Evidence of exposure to these endemic human respiratory viruses in the
      performing monkeys confirms human-to-primate transmission and suggests the
      possibility of primate-to-human transmission. Urban animal markets, the likely
      source of these performing monkeys, may represent an environment conducive to the
      mixing of animals and pathogens, making these monkeys a potential conduit for
      infectious agents passing from a variety of animals found in animal markets to
      humans. The potential significance of these results to human public health and
      the unique contexts of disease transmission associated with the urban ecology of
      the performance monkeys are discussed. Given the level of overseas travel, this
      potential threat is not confined solely to Asia.

PMID- 17038701
TI  - Pro-inflammatory cytokines and C-reactive protein are associated with
      undernutrition in the context of Schistosoma japonicum infection.
AB  - Schistosomiasis is associated with undernutrition, but the mechanisms involved
      remain unknown. We analyzed baseline and follow-up data from a longitudinal
      treatment-reinfection study in N = 477 Schistosoma japonicum-infected subjects 7
      20 years of age from Leyte, the Philippines. After baseline treatment with
      praziquantel, follow-up visits were scheduled every 3 months for 18 months;
      stool, venous blood, and anthropometric measurements were collected at each
      visit. Cytokine production by peripheral blood mononuclear cells (PBMCs)
      stimulated with specific S. japonicum antigens was measured once 4 weeks after
      treatment. After adjustment for confounders, S. japonicum intensity was
      associated with decreased serum albumin and Z-scores (all P < 0.05) and with
      increased serum C-reactive protein (CRP) and interleukin (IL)-6. CRP was
      associated with decreased albumin and Z-scores (all P < 0.01). Production of IL
      1b and tumor necrosis factor (TNF)-alpha in response to worm antigen was
      associated with decreased albumin (both P < 0.005) and height-for-age Z-score
      (TNF-alpha only, P = 0.05). S. japonicum-associated undernutrition may, in part,
      result directly from inflammation.

PMID- 17038703
TI  - Isolation of Rickettsia akari from eschars of patients with rickettsialpox.
AB  - Rickettsialpox is a cosmopolitan, mite-borne, spotted fever rickettsiosis caused
      by Rickettsia akari. The disease is characterized by a primary eschar, fever, and
      a papulovesicular rash. Rickettsialpox was first identified in New York City in
      1946 and the preponderance of recognized cases in the United States continues to
      originate from this large metropolitan center. The most recently isolated U.S.
      strain of R. akari was obtained more than a half century ago. We describe the
      culture and initial characterization of five contemporaneous isolates of R. akari
      obtained from eschar biopsy specimens from New York City patients with
      rickettsialpox. This work emphasizes the importance and utility of culture-and
      molecular-based methods for the diagnosis of rickettsialpox and other eschar
      associated illnesses.

PMID- 17038702
TI  - Molecular detection of Rickettsia felis, Rickettsia typhi and two genotypes
      closely related to Bartonella elizabethae.
AB  - A total of 56 fleas were collected from mice, rats, and one hedgehog in national
      parks of mainland Portugal and the Madeira Island. All fleas were tested for the
      presence of bacteria of the genera Rickettsia and Bartonella using PCR assays. In
      fleas from mainland Portugal, we detected Rickettsia felis in one Archaeopsylla
      erinacei maura flea and in one Ctenophtalmus sp. In five Leptopsylla segnis fleas
      taken from rats in the Madeira Island, we identified Rickettsia typhi. In
      addition, in four fleas from the genera Ornithophaga and Stenoponia collect from
      mice and a rat in mainland Portugal, we detected the presence of two new
      Bartonella genotypes closely related to Bartonella elizabethae. Our findings
      emphasize the potential risk of flea-transmitted infections in mainland Portugal
      and the Madeira archipelago, and extend our knowledge of the potential flea
      vectors of human pathogens.

PMID- 17038704
TI  - Immunologic tests in patients after clinical cure of visceral leishmaniasis.
AB  - The results of five serologic tests (ELISA using promastigote antigen [ELISAp]
      and recombinant K39 [ELISArK39] and K26 [ELISArK26] antigens, indirect
      immunofluorescence test using promastigote antigen [IIFT], and
      immunochromatographic tests using the rK39 antigen [TRALd]) and of the Montenegro
      skin test (MST) were analyzed in 41 individuals treated for kala-azar and living
      in Porteirinha, Minas Gerais, Brazil. The tests were carried out 1 week to 12
      years after specific treatment. All MSTs during the 8 months after treatment were
      negative, whereas after 1 year, 28 (84.8%) were positive. Negativity in all
      serologic tests was observed for 11 (26.8%) of the 41 individuals, whereas
      positivity in at least one test was observed for 70.3% of subjects evaluated > or
      = 2 years after treatment. With respect to each exam, positivity was 38.0% for
      TRALd, 61.9% for ELISA rK39, 47.6% for ELISA rK26, 38.0% for ELISAp, and 40.5%
      for IIFT. None of the individuals presented recurrence of the disease during the
      4 years of follow-up. The tests were repeated in 24 of the 41 individuals, after
      some time, and the results were the same in 33.3% of the cases. We conclude that
      serological tests for kala-azar might continue to be positive after treatment of
      the disease, although this does not indicate a poor prognosis or a poor
      therapeutic response.

PMID- 17038705
TI  - Loss of leishmanin skin test antigen sensitivity and potency in a longitudinal
      study of visceral leishmaniasis in Bangladesh.
AB  - Annual leishmanin skin test (LST) surveys were conducted in a visceral
      leishmaniasis-endemic Bangladeshi community from 2002 through 2004, using
      Leishmania infantum antigen from the same manufacturer and batch. In 2002, 530
      (35%) of 1,532 had positive LST results; the prevalence increased with increasing
      age. The LST result was positive in 24 (51%) of 47, 18 (72%) of 25, and 11 (85%)
      of 13 kala-azar patients treated in the previous 1-11, 12-23, and 24-35 months. A
      positive LST result in 2002 was associated with protection against subsequent
      kala-azar (P < 0.0001). In 2003-2004, decreased antigen sensitivity was observed.
      Among 686 participants, 34% were LST-positive in 2002, 29% in 2003, and 19% in
      2004. Of 63 cured kala-azar patients, 70% were positive in 2002, 53% in 2003, and
      only 30% in 2004. Among 171 participants tested with both antigens, L. infantum
      study antigen sensitivity was 70% compared with L. amazonensis antigen. Our data
      underscore the need for better production, standardization, and documentation of
      sensitivity, potency, and stability of leishmanin antigens.

PMID- 17038706
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces Leishmania major burdens in
      C57BL/6 mice.
AB  - Acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can suppress
      adaptive immunity. In this study, pre-exposure of Leishmania major-infected mice
      to TCDD caused a dose-dependent and unexpected decrease in parasite burdens on
      day 20 after infection. In contrast, TCDD-mediated lymphoid atrophy, suppressed
      antibody levels, and enhanced interleukin-2 production were observed as expected.
      These results suggest that TCDD may enhance resistance to L. major in the face of
      immune suppression.

PMID- 17038707
TI  - A prospective study of the effects of sustained vector surveillance following
      community-wide insecticide application on Trypanosoma cruzi infection of dogs and
      cats in rural Northwestern Argentina.
AB  - Domestic dogs were used as natural sentinels to assess prospectively the long
      term impact of selective, community-based spraying with pyrethroid insecticides
      after community-wide spraying on transmission of Trypanosoma cruzi in rural
      villages under surveillance between 1992 and 2002. In 2000 and 2002 light
      infestations by Triatoma infestans were recorded, and 523 dogs and cats were
      examined serologically or by xenodiagnosis. The prevalence of T. cruzi infection
      in dogs decreased from 65% at baseline to 8.9% and 4.7% at 7.5 and 10 years after
      sustained vector surveillance, respectively. The average annual force of
      infection dropped 260-fold from 72.7 per 100 dog-years at baseline to <0.3% in
      2002, as determined prospectively and retrospectively from the age-prevalence
      curve of native dogs born during surveillance. Multiple logistic regression
      analysis showed that prevalent cases in dogs in 2000 and 2002 were associated
      positively and significantly with the peak number of T. infestans caught in
      domestic areas at the dog's compound during its lifetime. The sustained decline
      in T. cruzi infections in dogs and cats is the result of selective, community
      based insecticide spraying that kept the abundance of infected T. infestans at
      marginal levels, fast host population turnover, and low immigration rates from
      areas with active transmission.

PMID- 17038708
TI  - Incidence, etiology, and impact of diarrhea among deployed US military personnel
      in support of Operation Iraqi Freedom and Operation Enduring Freedom.
AB  - A health assessment survey was collected from US military personnel deployed to
      the Middle East taking part in the "Rest and Recuperation" program or on
      temporary assignment to Camp As Sayliyah Doha, Qatar, from January to December
      2004. In addition, a concurrent clinic-based observational study was conducted to
      determine pathogen etiology and potential risk factors. From 28,322 health
      assessment surveys, overall self-reported incidence of diarrhea was 4.9 cases per
      100 person-months. Disease incidence increased with rank and was higher in Iraq
      compared with Afghanistan. During this period, 109 US military personnel with
      acute diarrhea and 85 asymptomatic personnel were enrolled in the observational
      study. Enterotoxigenic E. coli (ETEC) was the predominant pathogen (32%),
      followed by enteroaggregative E. coli (12%) and Salmonella spp. (6%). These data
      are consistent with previous reports implicating ETEC as the primary cause of
      acute diarrhea for military personnel deployed to this region.

PMID- 17038709
TI  - BCG vaccine effectiveness against Buruli ulcer: a case-control study in Benin.
AB  - BCG remains the only possible prophylactic intervention against Buruli ulcer
      (BU). Estimating its public health impact on BU control is an important issue. We
      conducted a case-control study to investigate the vaccine effectiveness of
      routine BCG vaccine against BU in southern Benin. From August 2002 to August
      2003, BCG vaccination status was obtained for 279 clinically diagnosed BU cases
      and 988 age- and sex-matched neighborhood controls. BCG coverage, which was
      estimated by the presence of a scar or a vaccination record, was 64.5% in cases
      and 67.2% in controls. There was no evidence of a protective effect of routine
      BCG vaccination against BU in southern Benin (vaccine effectiveness adjusted for
      socioeconomic status = 12%, 95% confidence interval = -24% to 37%).

PMID- 17038710
TI  - Bone health in children.

PMID- 17038711
TI  - Prevention of diabetes.

PMID- 17038712
TI  - X ray imaging goes digital.

PMID- 17038713
TI  - Preoperative staging for rectal cancer.

PMID- 17038714
TI  - Use of mobile phones in hospitals.

PMID- 17038717
TI  - UN questions China over organ harvesting.

PMID- 17038718
TI  - Dutch clinic is ordered to stop giving stem cell therapy.

PMID- 17038719
TI  - The importance of smelly feet and stinky cheese.

PMID- 17038721
TI  - New York plans to restrict trans fats in restaurants.

PMID- 17038723
TI  - Guideline calls for better treatment of atrial fibrillation.

PMID- 17038726
TI  - Failure to control mosquitoes has led to two fever epidemics in India.

PMID- 17038730
TI  - Doctors in Germany protest at a new restrictive law on tissue banks.

PMID- 17038731
TI  - NICE says anti-dementia drugs should be used only for moderate Alzheimer's
      disease.

PMID- 17038732
TI  - South Africa sidelines its health minister on AIDS issues.

PMID- 17038733
TI  - Ignorance about HIV is still high in many parts of Europe.

PMID- 17038735
TI  - Epileptic seizures can follow high doses of oral vardenafil.

PMID- 17038736
TI  - Acute renal failure.

PMID- 17038737
TI  - Investigating iron status in microcytic anaemia.

PMID- 17038738
TI  - ABC of obesity. Management: part II--drugs.

PMID- 17038739
TI  - NHS maternity units should not encourage commercial banking of umbilical cord
      blood.

PMID- 17038740
TI  - How to formulate research recommendations.

PMID- 17038742
TI  - Parachute approach to evidence based medicine: arguments are easily refuted.

PMID- 17038743
TI  - Parachute approach to evidence based medicine: as obvious as ABC.

PMID- 17038744
TI  - MRI in predicting curative resection of rectal cancer: defining a "window of
      opportunity" for laparoscopic surgery.

PMID- 17038745
TI  - MRI in predicting curative resection of rectal cancer: does post-neoadjuvant MRI
      have a role?

PMID- 17038746
TI  - MRI in predicting curative resection of rectal cancer: new dilemma in
      multidisciplinary team management.

PMID- 17038747
TI  - Belittlement and harassment of medical students: remedial training--ethics and
      sensitivity.

PMID- 17038748
TI  - Belittlement and harassment of medical students: is a source of medical
      education.

PMID- 17038749
TI  - Obesity is a wake up call for developing world too.

PMID- 17038750
TI  - Diagramming qualitative theories.

PMID- 17038751
TI  - Continuities and discontinuities in the experiences of felt and enacted stigma
      among women with HIV/AIDS.
AB  - In the post-1996 era, the effectiveness of antiviral therapies (such as highly
      active antiretroviral therapy [HAART]), which transformed HIV/AIDS into a more
      manageable disease, raised expectations that the disease's stigma would decrease.
      The authors compared focused-interview data from a pre-HAART (1994 to 1996) and a
      HAART-era (2000 to 2003) sample of African American, Puerto Rican, and White
      women living with HIV/AIDS to identify changes in stigma experiences and suggest
      reasons for continued stigmatization. In both eras, general stereotypes about
      HIV/AIDS, as well as gender- and race-related stereotypes about the disease, were
      identified. Internalizing any of these stereotypes was a necessary and sufficient
      condition for feeling stigmatized. Instances of enacted stigmatization were more
      frequent and intense in the pre-HAART era. Nevertheless, misinformation and
      irrational fears of contagion, which triggered stigmatizing behavior, persisted
      into the HAART era. This analysis revealed that although enacted stigmatization
      has decreased slightly, felt stigma remains a primary adaptational challenge
      facing women with HIV/AIDS.

PMID- 17038752
TI  - "Never again" stories of nurses: dilemmas in nursing practice.
AB  - The authors describe significant turning points immanent in "never again" stories
      that practicing nurses, having participated in previously, vowed not to allow to
      recur during future, similar situations. Nurses submitted written accounts of
      critical, "never again" situations. The authors used critical incident technique
      and employed Colaizzi's approach to reveal the essential structure. Patient
      outcomes were fatal, close calls, dehumanizing, or isolating. Never again stories
      incorporated ethical dilemmas, deficits in nurses' knowledge, lack of confidence
      in clinical abilities, and failure to act correctly. Patients' welfare was the
      center of accounts. Circumstances threatened patients' and family members' trust
      in nurses and other providers. Patients' wishes were denied because of haste,
      providers' arrogance, or providers' desire not to be inconvenienced. Nurses'
      emotions mirrored a sense of failed responsibility for patients. Regret was
      tempered by nurses' pledges. Critical incidents revealed dilemmas in which
      nurses' autonomous clinical practice was constrained by feelings of
      powerlessness.

PMID- 17038753
TI  - "Pull yourself up by your bootstraps": a response to depression in older adults.
AB  - Although depression is one of the most common problems among adults in primary
      care settings, many do not seek or adhere to the treatment regimens suggested by
      their providers. Understanding the cultural model surrounding depression and its
      treatment in older adults might provide insight into the development of more
      effective strategies for addressing the problem in the clinical setting. In this
      study, the authors conducted semi-structured interviews with adults over age 65.
      Personal responsibility for the management of depression emerged as a pervasive
      approach to dealing with depression. Older adults used orientational and movement
      metaphors to describe the process of moving out of depression. They viewed
      initiation and follow-through of this process as the sole responsibility of the
      depressed individual. This attitude might be rooted in the cultural experiences
      of this particular cohort of older adults and has implications for their use of
      physical and mental health services for depression.

PMID- 17038754
TI  - A contextual study of daily living strategies in neurocognitively impaired adults
      with schizophrenia.
AB  - Schizophrenia is a severe mental illness often recognized as a degenerative
      neurocognitive condition. For some with the disorder, the impairment is fairly
      mild, but for others, neurocognitive abilities can be severely compromised. In
      this study, 5 individuals with schizophrenia had been assessed through a
      laboratory-based neurocognitive battery as having severe impairment. Their
      neurocognitive status was unknown to the author, and she was able to observe
      daily tasks and ask questions about strategies they employed while completing
      tasks, and analyze the data without preconceptions about their status. This study
      was guided by notions of ecological validity, which is the comparison between lab
      tests and real-world functioning. Despite their cognitive deficits, these
      individuals had remarkable strengths, which included drawing supportive people
      into their worlds to fulfill their daily tasks. These data contribute to the
      rehabilitation literature and propose remedies for struggles of daily living when
      one has schizophrenia.

PMID- 17038755
TI  - Power imbalance and consumerism in the doctor-patient relationship: health care
      providers' experiences of patient encounters in a rural district in India.
AB  - The aim of this study is to explore health care providers' experiences and
      perceptions of their encounters with male and female patients in a rural district
      in India with special reference to tuberculosis (TB) care. The authors conducted
      semistructured interviews with 22 health care providers, 17 men and 5 women, from
      the public and private health care sectors. Findings reveal that doctors adopted
      an authoritarian as well as a consumerist approach in the medical encounter,
      indicating that power imbalances in the doctor-patient relationship are
      negotiable and subject to change. Gender was identified as an influencing factor
      of the doctor's dominance. A patient-centered approach, acknowledging patients'
      own experiences and shared decision making, is called for and should be included
      in TB control activities. This seems to be especially important for female
      patients, whose voices were not heard in the medical encounter.

PMID- 17038756
TI  - "I thought there was no hope for me": a behavioral intervention for urban mothers
      with problem drinking.
AB  - In this article, the authors evaluate the effects of a behavioral intervention
      for mothers with problem drinking who were infected with, or at risk for, HIV.
      They randomly selected 25 mothers from a larger longitudinal randomized
      controlled intervention trial for a qualitative interview. The authors found that
      mothers' participation in the program was facilitated by the development of a
      strong therapeutic alliance with the intervention facilitator and the use of a
      harm reduction approach toward alcohol and/or drug abuse. Mothers also reported
      that training in coping skills and the emphasis on parent-adolescent
      relationships were beneficial for program engagement and behavior change. The
      authors conclude from these results that treatment approaches that take into
      account the complexity of urban mothers' lives and substance use patterns can
      successfully engage and treat these women at high risk for adverse outcomes.

PMID- 17038758
TI  - Managing shame and stigma: case studies of female carers of people with AIDS in
      southern Thailand.
AB  - The authors of this article discuss the effects of shame and stigma on female
      caregivers of people living with AIDS in southern Thailand. They conducted a
      longitudinal ethnographic case study over 8 months and collected data using
      interviews, observations, field notes, and journaling. The authors performed
      qualitative content analysis and narrative analysis. Public judgment was created
      in a moral climate, framed by Buddhist precepts of correct and honorable
      behavior, with different levels of tolerance and stigmatization between men and
      women. Women caregivers engaged in concealing practices, deception, and
      withdrawal from social relationships to manage the effects of shame and stigma.

PMID- 17038757
TI  - Caught in a balancing act: parents' dilemmas regarding their ADHD child's
      treatment with stimulant medication.
AB  - The authors explored parents' perceptions of and everyday experiences with the
      stimulant medication used to treat their child's attention deficit hyperactivity
      disorder (ADHD) in this phenomenological study. They elicited experiences through
      semistructured interviews with 10 Canadian parents of children with ADHD. In the
      interviews, parents revealed the meaning the stimulant medication had taken on in
      the context of their everyday lives. Through the interview analysis, dilemma
      emerged as the dominant theme. Parents were caught in a dynamic balancing act, as
      they considered the medication's desirable and undesirable effects in various
      settings. In addition, parents shared their expectations regarding the
      medication's role in their child's future. The study's findings reinforce the
      necessity of further qualitative research in this area, given the growing number
      of families around the globe whose children have been diagnosed with ADHD.

PMID- 17038759
TI  - Orienting multiple interviewers: the use of an interview orientation and
      standardized interview.
AB  - An interviewer orientation protocol and standardized interview can be an
      effective way of orienting multiple interviews to qualitative research. A
      standardized interview involves an actor taught to portray a research participant
      consistently in several interview encounters. In this article, the authors
      describe the interview protocol, and the development and application of a
      standardized interview. The benefits of using a standardized interview as a
      formative method to orient multiple interviewers include assessing the
      interviewers' integration of the interview protocol, the nonverbal and verbal
      presentation of the interview process between interviewers, and the general flow
      of the interview from interviewer to interviewer. As more qualitative research is
      conducted using multiple interviewers, the method of an interview protocol and
      subsequent standardized interview might be helpful when orienting interviewers to
      the challenges and promises of conducting research using a critical framework.

PMID- 17038760
TI  - Comparison of verbal claims for natural health products made by health food
      stores staff versus pharmacists in Ontario, Canada.
AB  - BACKGROUND: This study tested the hypothesis that while there are no written
      medical claims existing for many NHP, such claims are made verbally, giving a
      false impression that these are proven medical products. OBJECTIVE: To compare
      the number and type of verbal claims for NHP made by pharmacists to those made by
      health food stores personnel. METHODS: Randomly selected Canadian pharmacies
      selling NHP and health food stores were visited and the staff was asked to
      recommend natural health products for the treatment of hypertension. RESULTS: All
      health food stores (n=20) but only 4 out of 38 pharmacies (p< 0.001) recommended
      NHP for the treatment of hypertension. A majority of health food store staff
      (70%) stated that NHP are superior or equal to medicinal drugs in treating
      hypertension based on efficacy. CONCLUSION: Unlike pharmacy practice, verbal
      claims are common practice in health food stores, despite the lack of either
      written claims and/or proof of efficacy for most of them. These may be a very
      effective approach given that 30-40% of North American adults are functionally
      illiterate. These verbal claims are often inappropriate and not evidence-based.

PMID- 17038761
TI  - Stabilization of the spark-discharge point on a sample surface by laser
      irradiation for steel analysis.
AB  - A combined technique with laser irradiation is suggested to control spark
      discharge for analytical use, having a unique feature that firing points of the
      spark discharge can be fixed by laser irradiation. Because the spark discharge
      easily initiates at particular surface sites, such as non-metallic inclusions,
      called selective discharge, the concentration of some elements sometimes deviates
      from their average one in spark discharge optical emission spectrometry.
      Therefore, stabilization of firing points on a sample surface could improve the
      analytical precision.

PMID- 17038763
TI  - Raman microspectroscopy/imaging study on phase-vanishing processes of fluorous
      biphase systems in microchannel-microheater chips.
AB  - Temperature-dependent phase-vanishing processes between perfluorohexane (FC-72)
      and n-heptane (C7H16, volume ratio of 1:1 and phase-vanishing temperature>41
      degrees C), were studied in a glass microchannel-microheater chip under solution
      flow conditions. Without applying a voltage to the heater at 21 degrees C, the
      two liquids in the microchannel were separated into two streams at a solution
      flow rate (v) of 0.975 cm/s, while the phase boundary between FC-72 and C7H16
      vanished in the downstream side of the heater at V=4.5 V. Then, we conducted
      Raman intensity imaging during the phase vanishing processes in the microchannel
      by monitoring the band at 756 (FC-72) or 1456 cm-1 (C7H16). At V=4.5 V and
      v=0.975 cm/s, although no phase boundary between the two liquids in the
      microchannel was observed, the relevant Raman intensity images indicated the
      inhomogeneous nature of the solution, and distribution of C7H16 to the FC-72
      phase along with solution flow was observed.

PMID- 17038762
TI  - A disposable, screen-printed electrode for the amperometric determination of
      azide based on the immobilization with catalase or tyrosinase.
AB  - A disposable, screen-printed electrode based on the immobilization of catalase or
      tyrosinase was developed to construct biosensors for the amperometric
      determination of azide. The determination principles for azide by these two
      methods are based on inhibiting the enzymatic consumption of an electrode
      detectable substance (hydrogen peroxide or catechol) on an enzyme-immobilized
      electrode. Both of these methods show a sensitive detection range and a short
      measuring time.

PMID- 17038764
TI  - Fluorescence lifetime imaging microscope consisting of a compact picosecond dye
      laser and a gated charge-coupled device camera for applications to living cells.
AB  - An inverted microscope was combined with a compact dye laser with a pulse width
      of <190 ps and an intensified charge-coupled device (ICCD) camera with a minimum
      gate width of 200 ps. The resulting fluorescence lifetime imaging microscope,
      which has a temporal resolution of 340 ps, was used to measure the fluorescence
      lifetime of polymer microspherers. The results indicated a fluorescence lifetime
      of 0.9 ns. The present analytical instrument was also employed in an evaluation
      of biological cells after labeling them with SYTO 13, a fluorescent dye.

PMID- 17038765
TI  - Application of total reflection X-ray fluorescence spectrometry to small glass
      fragments.
AB  - Total reflection X-ray fluorescence spectrometry (TXRF) has been applied for
      trace elemental analysis of small glass fragments. A small glass sample (a
      fragment with weight less than 0.5 mg) was decomposed by 100 microg of HF/HNO3
      acid; the material was condensed to 10 microl and was dried on a Si wafer. Since
      the size of the dried residue on the Si wafer was less than 1 cm in diameter, an
      incident X-ray beam with about 1 cm in width could effectively excite elemental
      components in such a small glass fragment. The precision of the present technique
      was checked by analyzing the glass fragments (<0.5 mg) from NIST SRM612; the
      relative standard deviations (RSD) of less than 8.1% were achieved for elemental
      ratios that were normalized by Sr. Fragments (<0.5 mg) obtained from 23 figured
      sheet glasses were used as samples for estimating the utility of this technique
      to forensic discrimination. Comparison of five elemental ratios of Ti/Sr, Mn/Sr,
      Zn/Sr, Rb/Sr, and Pb/Sr calculated from X-ray fluorescence spectra was effective
      in distinguishing glass fragments that could not be differentiated by their
      refractive indexes (RI).

PMID- 17038766
TI  - Interaction of [HgX4]2- with berberine by absorption and resonance Rayleigh
      scattering spectra and their analytical applications.
AB  - In a diluted H2SO4 solution, Hg(II) reacts with halide anions X- (including Cl-,
      Br- and I-) to form anionic complexes [HgX4]2- that can further react with
      berberine to form ion-association complexes of [Ber]2[HgX4]. As a result, the
      absorption spectra change, their maximum absorption wavelengths are at 230 nm for
      [Ber]2[HgCl4], 278 nm for [Ber]2[HgBr4] and 300 nm for [Ber]2[HgI4]. However,
      among the three complexes, only [Ber]2[HgI4] can lead to distinctly enhanced
      resonance Rayleigh scattering (RRS), and a new RRS spectrum appears. The maximum
      RRS wavelength is located at 397 nm, and the RRS intensity is proportional to the
      concentration of berberine in the range of 0-2.5 microg mL-1. The optimum
      conditions, the influence factors for the reaction and the effects of coexisting
      substances have been investigated. A new, simple and fast RRS method for the
      determination of berberine based on the ion-association reaction of [HgI4]2- with
      Ber+ was developed. The method has high sensitivity and good selectivity; the
      detection limit for berberine (3 sigma/K) is 7.22 ng mL-1. The method can be
      applied to the determination of berberine in some Chinese patent drug and the
      extracts of Coptis Chinensis. Furthermore, the mechanism of the reaction and the
      reasons for RRS enhancement have been discussed.

PMID- 17038767
TI  - Multivariate analysis for 1H-NMR spectra of two hundred kinds of tea in the
      world.
AB  - NMR measurements coupled with pattern-recognition analysis offer a powerful
      mixture-analysis tool for latent-feature extraction and sample classification. As
      fundamental applications of this analysis for mixtures, the 1H spectra of 176
      kinds of green, black, oolong and other tea infusions were acquired by a 500 MHz
      NMR spectrometer. Each spectrum pattern was analyzed by a multivariate
      statistical pattern-recognition method where Principal Component Analysis (PCA)
      was used in combination with Soft Independent Modeling of Class Analogy (SIMCA).
      SIMCA effectively selected variables that contribute to tea categorization. The
      final PCA resulted in clear classification reflecting the fermentation and
      processing of each tea, and revealed marker variables that include catechin and
      theanine peaks.

PMID- 17038768
TI  - Evaluation of the oxygen reduction activities of rare-earth oxide-supported
      silver catalysts using a channel flow double electrode.
AB  - The channel flow double electrode (CFDE) was used for the evaluation of the
      oxygen reduction activities in alkaline solution of rare-earth oxide-supported
      silver catalysts. The CFDE cell was modified for the experiment using the powder
      catalyst as a working electrode. In the present experiment, the silver electrode
      was supported with CeO2 in order to improve the performance of the oxygen
      reduction. The detecting electrode current for HO2- emitted from the working
      electrode was recorded simultaneously with the measurement of the i-E curve of
      each working electrode. Moreover, the average number of charge transfers n was
      calculated from the working and detecting electrode currents. The value of n for
      the oxygen reduction was approximately 4 for silver electrode supported with rare
      earth oxide, compared with the n value of pure silver that was smaller than 4. On
      the basis of these results, the mechanisms of oxygen reduction on these
      electrodes and role of the rare-earth oxide in alkaline solution were discussed.

PMID- 17038769
TI  - Speciation of antimony by preconcentration of Sb(III) and Sb(V) in water samples
      onto nanometer-size titanium dioxide and selective determination by flow
      injection-hydride generation-atomic absorption spectrometry.
AB  - A novel method for prevention of the oxidation of Sb(III) during sample
      pretreatment, preconcentration of Sb(III) and Sb(V) with nanometer size titanium
      dioxide (rutile) and speciation analysis of antimony, has been developed.
      Antimony(III) could be selectively determined by flow injection-hydride
      generation-atomic absorption spectrometry, coexisting with Sb(V). Trace Sb(III)
      and Sb(V) were all adsorbed onto 50 m g TiO2 from 500 ml solution at pH 3.0
      within 15 min, then eluted by 10 ml of 5 mol/l HCl solution. One eluent was
      directly used for the analysis of Sb(III); to the other eluent was added 0.5 g KI
      and 0.2 g thiourea to reduce Sb(V) to Sb(III), then the mixture was used for the
      determination of total antimony. The antimony(V) content is the mathematical
      difference of the two concentrations. Detection limits (based on 3sigma of the
      blank determinations, n=11) of 0.05 ng/ml for Sb(III) and 0.06 ng/ml for Sb(V),
      were obtained.

PMID- 17038770
TI  - Determination of poly(3-hydroxybutyrate) using a combination of enzyme-based
      biosensor and alkaline hydrolysis.
AB  - The combination of an enzyme-based biosensor and alkaline hydrolysis was
      developed for the measurement of poly(3-hydroxybutyrate) (PHB). The principle of
      the determination is based on that the alkaline condition converts PHB to produce
      its monomer, 3-hydroxybutyrate (3-HB), which generates a detectable current
      signal by an amperometric biosensor through coupled two-enzyme reactions on an
      electrode. This method takes less than 40 min, and results in a linear detection
      range of 0.5-110 mg L-1 PHB with a detection limit of 0.3 mg L-1 by the saturated
      production of 3-HB; it can also take less than 15 min and result in a linear
      detection range of 1.0-160 mg L-1 PHB with a detection limit of 0.5 mg L-1 by a
      part production of 3-HB. The method also shows simple operation and high
      reproducibility.

PMID- 17038771
TI  - Triethylene glycol ether end-grafted carbosilane dendrimer: a potential ionophore
      for potassium ion recognition.
AB  - The performance of a newly synthesized carbosilane dendrimer bearing four
      triethylene glycol ether (TEG) units, Si(CH2CH2CH2Si(Me)2CH2CH2CH2(OCH2CH2)3Me)4
      (1), as ionophores in ion-selective electrodes has been investigated.
      Optimization of the plasticized polyvinyl chloride membrane composition has
      produced electrodes that exhibit a Nernstian response for potassium ions. The
      best general characteristics exhibited by the electrodes were found when the
      membrane composition ratio of DPE:1:NaTPB:PVC 60:3:2:35 (wt%) was used. The
      response of the electrode was linear with a Nernstian slope of 58.3 mV/decade
      over the K+ ion concentration range of 1.9x10(-7) to 1.0x10(-1) M with a
      detection limit of 3.1x10(-7) M. The response time to achieve a 95% steady
      potential for the K+ concentration ranging from 1.0x10(-1) to 1.0x10(-8) M was
      less than 10 s, and it was found that the electrode is suitable for use within a
      pH range of 5.5-8.5. The selectivity coefficients (log KPotK+,Mn+)), which were
      determined by the fixed interference method, showed good selectivity for K+
      against most of the interfering cations. The influence of this selective ion
      binding behavior using electrospray ionization time-of-flight (ESI-TOF) mass
      spectrometric studies is discussed.

PMID- 17038772
TI  - A PVC plasticized sensor for Ni(II) ion based on a simple ethylenediamine
      derivative.
AB  - A new PVC membrane ion selective electrode which is highly selective towards
      Ni(II) ions was constructed using a Schiff base containing a binaphthyl moiety as
      the ionophore. The sensor exhibited a good Nernstian response for nickel ions
      over the concentration range 1.0x10(-1)-5.0x10(-6) M with a lower limit of
      detection of 1.3x10(-6) M. It has a fast response time and can be used for a
      period of 4 months with a good reproducibility. The sensor is suitable for use in
      aqueous solutions in a wide pH range of 3.6-7.4 and works satisfactorily in the
      presence of 25% (v/v) methanol or ethanol. The sensor shows high selectivity to
      nickel ions over a wide variety of cations. It has been successfully used as an
      indicator electrode in the potentiometric titration of nickel ions against EDTA
      and also for the direct determination of nickel content in real samples: effluent
      samples, chocolates and hydrogenated oils.

PMID- 17038773
TI  - A selective membrane electrode for lanthanum(III) ion based on a hexaaza
      macrocycle derivative as ionophore.
AB  - We have developed a highly La(III)-selective PVC membrane electrode based on a
      hexaaza macrocycle, 8,16-dimethyl-6,14-diphenyl-2,3,4:10,11,12-dipyridine
      1,3,5,9,11,13-hexaazacyclohexadeca-3,5,8,11,13,16-hexaene [Bzo2Me2Pyo2(16)
      hexaeneN6] (I) as membrane carrier, dibutylbutyl phosphonate (DBBP) as solvent
      mediator and sodium tetraphenylborate (NaTPB) as lipophilic additive. The best
      performance was given by the membrane of macrocycle I having a composition
      10:260:5:120 (I:DBBP:NaTPB:PVC). The electrode exhibits a Nernstian response to
      La(III) ion in the concentration range 1.0x10(-1)-7.94x10(-7) M with a slope of
      19.8+/-0.2 mV/decade of concentration and a detection limit of 5.62x10(-7) M. The
      response time of the sensor is 12 s and it can be used over a period of 4 months
      with good reproducibility. The electrode works well over a pH range of 2.5-10.0
      and in partially non-aqueous medium with up to 30% organic content. The sensor
      was also used as an indicator electrode in potentiometric titration of La(III)
      ions with EDTA and for determining La(III) concentration in real samples.

PMID- 17038774
TI  - Highly selective iodide electrode based on the copper(II)-N,N'-bis(salicylidene)
      1,2-bis(p-aminophenoxy)ethane tetradentate complex.
AB  - In this paper, a new PVC-based liquid-membrane anion-selective electrode based on
      a copper(II) of N,N'-bis(salicylidene)-1,2-bis(p-aminophenoxy)ethane tetradentate
      complex (Cu(II)BBAP) is described, which displays a preferential potentiometric
      response to iodide ion at pH 2.0 and an anti-Hofmeister selectivity sequence: I
      >SCN->ClO4->NO2->H2PO4->NO3->SO4(2-)>Br->Cl-. The electrode exhibits a near
      Nernstian potential linear range of 8.2x10(-7)-1.0x10(-1) M with a detection
      limit of 5.3x10(-7) M and a slope of -58.8 mV per decade. The A.C. impedance
      technique and the UV/Vis spectroscopy technique were used to analyze the response
      mechanism. The electrode could be applied to determine iodide in medicine
      analysis, and the obtained results were fairly satisfactory.

PMID- 17038775
TI  - Determination of trace levels of diosmin in a pharmaceutical preparation by
      adsorptive stripping voltammetry at a glassy carbon electrode.
AB  - A systematic study on the electrochemical behavior of diosmin in Britton-Robinson
      buffer (pH 2.0-10.0) at a glassy carbon electrode (GCE) was made. The oxidation
      process of the drug was found to be quasi-reversible with an adsorption
      controlled step. The adsorption stripping response was evaluated with respect to
      various experimental conditions, such as the pH of the supporting electrolyte,
      the accumulation potential and the accumulation time. The observed anodic peak
      current at +0.73 V vs. Ag/AgCl reference electrode increased linearly over two
      orders of magnitude from 5.0x10(-8) M to 9.0x10(-6) M. A limit of detection down
      to 3.5x10(-8) M of diosmin at the GCE was achieved with a mean recovery of 97+/
      2.1%. Based on the electrochemical data, an open-circuit accumulation step in a
      stirred sample solution of BR at pH 3.0 was developed. The proposed method was
      successfully applied to the determination of the drug in pharmaceutical
      formulations. The results compared favorably with the data obtained via
      spectrophotometric and HPLC methods.

PMID- 17038776
TI  - Preparation and evaluation of uniform-size (-)-ephedrine-imprinted polymeric
      microspheres by multi-step swelling and suspension polymerization.
AB  - Ephedrine-imprinted polymeric microspheres have been prepared in an aqueous
      system by multi-step swelling and suspension polymerization, using methacrylic
      acid (MAA) as a functional monomer, and ethylene glycol dimethacrylate (EGDMA) as
      a cross-linker. Scanning electron microscopy (SEM) was used as a means to
      identify the structure features of the obtained polymers. Further, we examined
      the recognition mechanism of the polymers and the influences of some
      chromatographic conditions, such as the mobile-phase composition, flow-rate,
      column temperature and sample amount on the retentivity and selectivity for (-)
      ephedrine and (+)-ephedrine. The results reveal that stable macroporous polymer
      beads with good size monodispersity were obtained, the average size of which was
      3-5 microm. Baseline chiral separation of the template isomers was achieved on a
      short column (50 mmx4.6 mm i.d.) when the prepared polymer beads were used as a
      stationary phase, while the non-imprinted polymers (NIPs) did not show such
      ability. The optimized chromatographic condition was as follows: acetonitrile
      acetic acid (99.8/0.2, v/v) as the mobile phase; sample amount, 40-80 microg;
      flow rate, 1.0 ml min-1; and column temperature, room temperature, respectively.
      It is assumed that two classes of binding sites exist in the porous polymers, one
      being hydrophilic binding sites, the other being hydrophobic binding sites.

PMID- 17038777
TI  - UV irradiation controlled cold vapor generation using SnCl2 as reductant for
      mercury speciation.
AB  - A simple and ultrasensitive method, which was based on cold vapor generation
      (CVG) coupled to atomic fluorescence spectrometry (AFS), was proposed for
      speciation analysis of inorganic mercury (Hg2+) and methylmercury (MeHg) in water
      samples. In the presence of UV irradiation, all the mercury (MeHg+Hg2+) in a
      sample solution can be reduced to Hg0 by SnCl2; without UV irradiation, only Hg2+
      species can be determined. So the concentration of MeHg can be obtained from the
      difference of the total mercury and Hg2+ concentration; thus, speciation analysis
      of Hg2+ and MeHg was simply achieved without chromatographic separation. Under
      the optimized experimental conditions, the limits of detection were 0.01 ng mL-1
      for both Hg2+ and MeHg. The sensitivity and limit of detection were not dependent
      on the mercury species, and a simple Hg2+ aqueous standard series can be used for
      the determination of both Hg2+ and MeHg.

PMID- 17038779
TI  - Determination of trace impurities in high-purity cadmium by high-resolution
      inductively coupled plasma mass spectrometry.
AB  - Trace impurities in high-purity cadmium were determined by high-resolution
      inductively coupled plasma mass spectrometry (HR-ICP-MS). To overcome some
      potentially problematic spectral interference, measurements were acquired in both
      medium and high-resolution modes. The matrix effects due to the presence of
      excess HCl and cadmium were evaluated. The optimum conditions for the
      determination were tested in this experiment and discussed. The detection limits
      ranged from 0.01 to 0.27 microg g-1, depending on the elements. The results for
      the determination of 22 trace elements in high-purity cadmium are presented.

PMID- 17038778
TI  - Ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide
      molecules by gold nanoparticles with silver enhancement.
AB  - An ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide
      molecules by gold nanoparticles with silver enhancement has been developed. The
      hybridization products from the target polynucleotides with biotin-labeled probes
      and gold nanoparticle-functioned oligonucleotides were immobilized to microplates
      via avidin-biotin system, and the absorbance signals of gold nanoparticles were
      amplified by silver enhance solution. This sandwich colorimetric assay can detect
      as few as 600 molecules for single-strand oligonucleotides and as few as 6000
      molecules for double-strand polynucleotides in a 50 microL reaction system.

PMID- 17038780
TI  - Multiple-element detection in aqueous solution and seawater by using an on-line
      preconcentration method for inductively coupled plasma mass spectrometry.
AB  - Inductively coupled plasma-mass spectrometry (ICP-MS) incorporated with an on
      line preconcentration system was used to determine trace amounts of ten metals
      including Ni, Cu, Zn, Rh, Ag, Cd, In, Au, Tl, and Pb in aqueous solutions and
      seawater. These metals, which formed the complexes, were retained in a sorbent
      microcolumn, followed by elution with methanol through a desolvation unit, which
      was capable of removing 83% of methanol. The limits of detection for these
      elements were determined simultaneously to be in the range from 3 to 20 ng/L.

PMID- 17038782
TI  - [Glucose-induced insulin secretion independent of ATP-sensitive K+ channels].

PMID- 17038783
TI  - [H2S production by L-cysteine metabolism inhibits insulin release].

PMID- 17038784
TI  - [SOX6 attenuates glucose-stimulated insulin secretion by repressing PDX1
      transcriptional activity].

PMID- 17038785
TI  - [PPAR delta and metabolic syndrome].

PMID- 17038786
TI  - [Decreased PPARs activity mediated induction of anoikis and inability of cell
      adhesion and invasion in colorectal carcinoma cells].

PMID- 17038787
TI  - [PPAR gamma ligand pioglitazone as a therapeutic strategy in nonalcoholic
      steatohepatitis (NASH)].

PMID- 17038788
TI  - [Preparation of parotid acinar cells].

PMID- 17038789
TI  - [Observation and recording of mouse jaw movements with a novel restrictor system
      and a behavioral check list].

PMID- 17038790
TI  - [Basis of anti-glaucoma agents].

PMID- 17038791
TI  - [Clinical application of glaucoma medications].

PMID- 17038792
TI  - [Pharmacological and clinical profile of silodosin (URIEF Cap. 2 mg, 4 mg)].

PMID- 17038793
TI  - Sex chromosome-linked genes in plants.
AB  - Recent studies of plant sex chromosome-linked genes have revealed many
      interesting characteristics, although there are limited reports about
      heteromorphic sex chromosomes in flowering plants. Sex chromosome-linked genes in
      angiosperms have been characterized mainly in the dioecious plant Silene
      latifolia. Although all such genes were isolated from transcripts of male flower
      buds of S. latifolia, most seem to be housekeeping genes except for the petal-
      and stamen-specific MADS box gene on the Y chromosome (SlAP3Y) and the male
      reproductive organ-specific gene on the X chromosome (MROS3X). Recent
      evolutionary studies have revealed at least three evolutionary strata on the X
      chromosome that are related to stepwise loss of recombination between the sex
      chromosomes. Moreover, genetic maps showed conservation of gene organization on
      the X chromosome in the genus Silene and substantial pericentric inversion
      between the X and Y chromosomes of S. latifolia during evolution. A comparison
      between paralogs on the sex chromosomes revealed that introns of the Y-linked
      genes are longer than those of X-linked paralogs. Although analyses of sex
      chromosome-linked genes suggest that degeneration of the Y chromosome has
      occurred, the Y chromosome in flowering plants remains the largest in the male
      genome, unlike that of mammals. Accumulation of repetitive sequences and the
      entire chloroplast genome on the Y chromosome appear to have contributed to this
      large size. However, more detailed studies will be required to help explain the
      basis for the fact that heteromorphic sex chromosomes in angiosperms are large.

PMID- 17038795
TI  - Characterization of DNA methyltransferase genes in Brassica rapa.
AB  - DNA methylation is essential for normal development and plays important roles in
      regulating gene expression in plants. Analysis of the key enzymes catalyzing DNA
      methylation is important to understand epigenetic phenomena. In this study, three
      putative methyltransferase genes, BrMET1a, BrMET1b, and BrCMT, were isolated from
      a genome library of Brassica rapa. Structural conservation of the amino acid
      sequence between BrMET1a/BrMET1b and AtMET1 and that between BrCMT and AtCMT3
      suggests that they may function as DNA methyltransferase. BrMET1a was expressed
      in vegetative and reproductive organs, while BrMET1b was expressed only in
      pistils, indicating that these two genes have different functions. BrCMT was
      expressed especially in stamens at the stage of 2-4 days before anthesis. We
      isolated three DNA methyltransferase genes in Brassica rapa and indicated
      differences of expression patterns of these DNA methyltransferase genes and
      expression levels in different tissues and developmental stages, suggesting that
      these genes might play important roles in epigenetic gene regulation in B. rapa.

PMID- 17038794
TI  - Expression of germination-related enzymes, CspA, CspB, CspC, SleC, and SleM, of
      Clostridium perfringens S40 in the mother cell compartment of sporulating cells.
AB  - In Clostridium perfringens S40, spore germination-specific enzymes are
      synthesized during sporulation. Previous reports have demonstrated that two
      cortex-lytic enzymes, SleC and SleM, and a component of germination-specific
      protease, CspC, are located outside the cortex as an integral part of the dormant
      spore. In the present study, we examined the time and compartment of these
      enzymes' gene expression using reverse transcription-PCR (RT-PCR) and
      fluorescence microscopy on green fluorescence protein (GFP)-fused proteins. These
      results suggested that CspABC, SleC, and SleM are synthesized in the mother cell
      compartment of sporulating cells, probably at stages II approximately III of
      sporulation, and that the expression of cspABC genes is tricistronic.

PMID- 17038796
TI  - Genetic variations in the chloroplast genome and phylogenetic clustering of
      Lycoris species.
AB  - The genus Lycoris of Amaryllidaceae comprises approximately 20 species that are
      distributed only in the moist warm temperate woodlands of eastern Asia. The
      objectives of this study were: (1) to clarify the phylogeny of the Lycoris
      species by using the definitive DNA sequencing method and (2) to examine the
      possible maternal donor of the hybrid origin Lycoris species and the Japanese
      triploid strains of Lycoris radiata var. radiata. The nucleotide sequence of the
      maturase K (matK) gene and the noncoding intergenic spacer (IGS) between the atpB
      and rbcL genes in the chloroplast genome were determined in a total of 27 strains
      of 11 species of the genus Lycoris. Variation among taxa was mainly due to
      nucleotide substitution, although deletions and an insertion were found in the
      IGS. For two chloroplast regions, the phylogenetic trees showed essentially
      similar topology, indicating the existence of four clades, I, II, III, and IV.
      For all the species except L. radiata, intraspecific variation was smaller than
      interspecific variation. For L. radiata, triploid strains were divided into
      clades I and II, and diploid strains were divided into clades I and IV. This
      implies that the diploid species of L. radiata var. pumila is a probable
      ancestral species. The clustering indicated that the chloroplast genome has not
      evolved in parallel with the karyotype in genus Lycoris. Regarding the hybrid
      origin species, the maternal parents of L. squamigara, L. albiflora and L. rosea
      were revealed to be L. longituba, L. radiata and L. radiata var pumila,
      respectively. We also suggest that a diploid strain of L. radiata var. pumila in
      clade I might be a candidate of the maternal donor of the Japanese triploid
      strains. A possible model of the maternal donor of Lycoris species is proposed.

PMID- 17038797
TI  - Complete assignment of structural genes involved in flavonoid biosynthesis
      influencing bulb color to individual chromosomes of the shallot (Allium cepa L.).
AB  - We analyzed Japanese bunching onion (Allium fistulosum L.) - shallot (Allium cepa
      L. Aggregatum group) alien chromosome addition lines in order to assign the genes
      involved in the flavonoid biosynthesis pathway to chromosomes of the shallot. Two
      complete sets of alien monosomic additions (2n = 2x + 1 = 17) were used for
      determining the chromosomal locations of several partial sequences of candidate
      genes, CHS, CHI, F3H, DFR, and ANS via analyses of PCR-based markers. The results
      of DNA marker analyses showed that the CHS-A, CHS-B, CHI, F3H, DFR, and ANS genes
      should be assigned to chromosomes 2A, 4A, 3A, 3A, 7A, and 4A, respectively. HPLC
      analyses of 14 A. fistulosum - shallot multiple alien additions (2n = 2x + 2 - 2x
      + 7 = 18 - 23) were conducted to identify the anthocyanin compounds produced in
      the scaly leaves. A direct comparison between the genomic constitution and the
      anthocyanin compositions of the multiple additions revealed that a 3GT gene for
      glucosylation of anthocyanidin was located on 4A. Thus, we were able to assign
      all structural genes involved in flavonoid biosynthesis influencing bulb color to
      individual chromosomes of A. cepa.

PMID- 17038798
TI  - Molecular cloning and characterization of the mouse Na+ sulfate cotransporter
      gene (Slc13a4): Structure and expression.
AB  - Sulfate is an essential ion required for numerous functions in mammalian
      physiology. Due to its hydrophilic nature, cells require sulfate transporters on
      their plasma membranes to allow entry of sulfate into cells. In this study, we
      identified a new mouse Na(+)-sulfate cotransporter (mNaS2), characterized its
      tissue distribution and determined its cDNA and gene (Slc13a4) structures. mNaS2
      mRNA was expressed in placenta, brain, lung, eye, heart, testis, thymus and
      liver. The mouse NaS2 cDNA spans 3384 nucleotides and its open frame encodes a
      protein of 624 amino acids. Slc13a4 maps to mouse chromosome 6B1 and contains 16
      exons, spanning over 40 kb in length. Its 5'-flanking region contains CAAT- and
      GC-box motifs and a number of putative transcription factor binding sites,
      including GATA-1, MTF-1, STAT6 and HNF4 consensus sequences. This is the first
      study to define the tissue distribution of mNaS2 and resolve its cDNA and gene
      structures, which will allow us to investigate mNaS2 gene expression in vivo and
      determine its role in mammalian physiology.

PMID- 17038799
TI  - Seasonal fluctuation in susceptibility to insecticides within natural populations
      of Drosophila melanogaster. II. Features of genetic variation in susceptibility
      to organophosphate insecticides within natural populations of D. melanogaster.
AB  - To elucidate genetic variation in susceptibility to organophosphate insecticides
      within natural populations of Drosophila melanogaster, we conducted an analysis
      of variance for mortality data sets of isofemale lines (10-286 lines) used in the
      previous studies. Susceptibility of isofemale lines to the three organophosphate
      insecticides was continuously distributed within each natural population, ranging
      from susceptible to resistant. Analysis of variance showed highly significant
      variation among isofemale lines in susceptibility to each insecticide for each
      natural population. Significant genetic variances in susceptibility to the three
      chemicals were estimated for the Katsunuma population; 0.0529-0.2722 for
      malathion, 0.0492-0.1603 for prothiophos, and 0.0469-0.1696 for fenitrothion.
      Contrary to the consistent seasonal tendency towards an increase in mean
      susceptibility in the fall, reported in the previous study, genetic variances in
      susceptibility to the three organophosphates did not change significantly in 1997
      but tended to increase by 2- to 5-times in 1998. We tested whether both the
      observed situations, maintenance and increase in genetic variance in
      organophosphate resistance, can be generated under circumstances in which the
      levels of resistance to the three organophosphates tended to decrease, by
      conducting a simulation analysis, based on the hypothesis that resistant
      genotypes have lower fitnesses than susceptible ones under the density
      independent condition. The simulation analysis generally explained the pattern in
      the mean susceptibility and genetic variances in susceptibility to the three
      organophosphates, observed in the Katsunuma population of D. melanogaster. It was
      suggested that the differences in the frequencies of resistance genes in the
      summer population could affect the patterns in genetic variance in
      organophosphate resistance in the fall population.

PMID- 17038800
TI  - Chromosome-specific satellite sequences in Turritis glabra.
AB  - Two novel repetitive sequence families were isolated from Turritis glabra (2n =
      2x = 12). These two repeat families are similar to those of centromeric repeats
      in Arabidopsis thaliana, are co-localized on one chromosome pair, and differ by
      about 20% from each other. Phylogenetic analysis revealed that the two repeat
      families of T. glabra are more similar to each other than to the centromeric
      repeat families of other Arabidopsis and related species. The relationships of
      satellite sequences reflected the species phylogeny, indicating that the
      replacement of satellite sequences has occurred in each species lineage
      independently, and shared variants could not have existed for a long time between
      species.

PMID- 17038801
TI  - The role of UvrD in RecET-mediated illegitimate recombination in Escherichia
      coli.
AB  - To study the mechanism of RecET-mediated illegitimate recombination, we examined
      the formation of lambdabio-transducing phage in Escherichia coli in the presence
      or absence of UV irradiation. We have previously reported that coexpression of
      RecE and RecT enhances the frequency of recA-independent illegitimate
      recombination. RecJOR proteins are required for this RecET-mediated illegitimate
      recombination, and RecQ suppresses it. Here, we showed that the frequencies of
      both spontaneous and UV-induced RecET-mediated illegitimate recombination events
      are reduced by a uvrD mutation. It should be noted that UvrD is required for
      illegitimate recombination only in the presence, but not in the absence, of
      RecET. In contrast, frequencies of RecET-mediated illegitimate recombination were
      not affected by ruvAB, ruvC, recG, and recN mutations. The frequency of
      spontaneous and UV-induced illegitimate recombination in the uvrD recR double
      mutant was comparable to that of the uvrD single mutant, suggesting that UvrD
      works at the same step as RecR in the RecET-mediated recombination pathway.
      Nucleotide sequence analyses of the recombination junctions showed that RecET
      mediated illegitimate recombination detected in UvrD-deficient strain is short
      homology-dependent. Based on these and previous results, we propose a model for
      the role of UvrD on RecET-mediated illegitimate recombination.

PMID- 17038802
TI  - Beneficial action of 2,4,4-trimethyl-3-(15-hydroxypentadecyl)-2-cyclohexen-1-one,
      a novel long-chain fatty alcohol, on diabetic hypoalgesia and neuropathic
      hyperalgesia.
AB  - The effects of 2,4,4-trimethyl-3-(15-hydroxypentadecyl)-2-cyclohexen-1-one
      (tCFA15) on diabetic hypoalgesia and neuropathic hyperalgesia were examined.
      Treatments of streptozotocin (STZ)-pretreated mice with tCFA15 (8 - 40 mg/kg,
      i.p.) for 7 days significantly reversed the depressed inflammatory nociceptive
      licking response in the formalin test. In addition, similar drug treatments and
      dosing in 7-day postoperative neuropathic pain model rats (prepared by the method
      of Bennett and Xie) yielded a similarly favorable outcome by significantly
      reversing decreased nociceptive thresholds in the paw pressure test. These
      results suggest that tCFA15 may have the potential to normalize sensory nerve
      abnormalities induced in experimental diabetes and nerve injury.

PMID- 17038803
TI  - Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its
      alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain.
AB  - DJ-1 has multiple functions and its dysfunction may be linked to the onset of
      familial Parkinson's disease PARK7. However, the function and distribution of DJ
      1 is unclear. In this study, we determined DJ-1 distribution and change after
      intranigral injection of 6-hydroxydopamine (6-OHDA). Although distribution of DJ
      1 immunoreactivity was not changed in cerebral cortex and striatum, 6-OHDA caused
      increase of DJ-1 in the particulate fraction and decrease in the cytosolic
      fraction in substantia nigra. At that time, DJ-1 shifted to acid forms. These
      results suggest that distributional changes, translocation, and acidic shift of
      DJ-1 may be compensatory responses to protect against 6-OHDA-induced oxidative
      stress.

PMID- 17038804
TI  - Effect of gestational exposure to nonylphenol on the development and fertility of
      mouse offspring.
AB  - Nonylphenol (NP), a kind of environmental chemical, is thought to imitate
      endogenous hormones, inhibit the actions of hormones, and induce reproductive
      abnormalities. A number of experimental animals, usually rats, have been used to
      evaluate the potential reproductive toxicity of NP. However, the findings of
      previous studies were contradictory in some cases. Therefore, we used ICR mice as
      a biomodel for in utero study of NP. After mating, 8- to 12-week-old females were
      assigned to four groups (n=8) for subcutaneous injections from day 5 to 20 of
      gestation. Group I animals received corn oil alone as a control, while the mice
      of groups II, III and IV received NP at concentrations of 1/1000, 1/100 and 1/10
      of the LD(50), respectively. A dose-dependent decrease was observed in terminal
      body weights of males of the F1 generation; however, a very small negative effect
      was only found in the females of the NP1/10 group. No significant effect was
      found on the liver weights of both sexes. The weights of the testis and
      epididymis were slightly decreased in the NP1/10 group. The NP1/100 treatment
      increased ovary weight considerably. The uterus weight tended to be increased in
      the NP treatment groups; however, there were large variations. The gestational
      exposure of the groups had no significant effect on the rate of pregnancy (94.4
      100%) and the number of fetuses per litter (13.6-14.3 males, 12.3-13.7 females)
      compared with the control group. However, the overall mortality of
      fetuses/embryos was increased considerably in the NP1/100 (male: 13.9%) and
      NP1/10 (female: 9.8%) groups. These results suggest that exposure to NP in utero
      possibly affects the body weight and some reproductive organ weights, but does
      not influence the potential fertility of the F1 generation.

PMID- 17038805
TI  - Nuclear accumulation and activation of nuclear factor kappaB after split-dose
      irradiation in LS174T cells.
AB  - Although radiation-induced gene expression has been extensively studied, most of
      the studies to date have focused on that after single-dose irradiation. As split
      dose irradiation, rather than single-dose irradiation, is usual in clinical
      situations, we investigated the effects of split-dose irradiation on nuclear
      factor kappaB (NF-kappaB) in the human rectum carcinoma cell line, LS174T. After
      either single- or split-dose irradiation with a different interval, nuclear
      localization of NF-kappaB was examined by Western blot and immunofluorescence and
      its DNA-binding activity was measured by ELISA-based assay. Irradiation-induced
      NF-kappaB nuclear accumulation and DNA binding activity increased in a dose
      dependent manner. The peak of NF-kappaB nuclear accumulation and DNA binding
      activity was seen 2 to 6 hours after a single dose of 4 Gy irradiation and
      returned to control levels after 12 hours. In split-dose irradiation, NF-kappaB
      activity was similar after the first and second doses of 4 Gy irradiation
      separated by 12 hours. In addition, NF-kappaB activity was decreased by
      lengthening the interval between irradiation. The cell survival, which was
      assessed by colony formation assay, showed inverse correlation to this: the
      surviving fraction was higher after split-dose irradiation than after single-dose
      irradiation of the same total dose and it increased as the interval between
      irradiation was lengthened. Thus the present results showed a correlation between
      NF-kappaB activation and the repair of sublethal damage in split-dose
      irradiation.

PMID- 17038806
TI  - [Innate immune recognition of viral infection].
AB  - Toll-like receptors (TLRs) are key molecules of the innate immune systems, which
      detect conserved structures found in a broad range of pathogens and triggers
      innate immune responses. A subset of TLRs recognize viral components and induce
      antiviral responses by producing type I interferons. Whereas TLR2 and TLR4
      recognize viral components at the cell surface, TLR3, TLR7, TLR8 and TLR9 are
      exclusively expressed in endosomal compartments. After phagocytes internalize
      viruses or virus-infected apoptotic cells, viral nucleic acids are released in
      phagolysosomes and are recognized by these TLRs. Recent reports have shown that
      hosts also have a mechanism to detect replicating viruses in the cytoplasm in a
      TLR-independent manner. In this review, we focus on the viral recognition by
      innate immunity and the signaling pathways.

PMID- 17038807
TI  - [Study of animal viruses in yeast].
AB  - Yeast is often considered to be a model eukaryotic organism, in a manner
      analogous to E. coli as a model prokaryotic organism. Yeast has been extensively
      characterized and the genomes completely sequenced. Despite the small genome
      size, yeast displays most of features of higher eukaryotes. The facts that most
      of cellular machinery is conserved among different eukaryotes and that the
      powerful technologies of genetics and molecular biology are available have made
      yeast model eukaryotic cells in biological and biomedical sciences including
      virology. Cumulative data indicate that yeast can be a host for animal viruses. I
      briefly describe yeast gene expression and review viral replication in yeast.
      Great discovery include complete replication of animal viruses and production of
      virus-like particle vaccines in yeast. Current studies on yeast focus on
      identification of host factors and machinery used for viral replication. The
      studies are based on traditional yeast genetics and genome-wide identification
      using a complete set of yeast deletion strains.

PMID- 17038808
TI  - [Development of intranuclear inclusions of human polyomavirus JC. Capsid proteins
      are assembled into virions at the PML nuclear bodies].
AB  - Human polyomavirus JC (JCV) is a causative agent for progressive multifocal
      leukoencephalopathy, a fatal demyelinating disorder. The viruses form
      intranuclear viral inclusions in infected oligodendrocytes. The outer capsid of
      JCV is thought to be composed of 360 molecules of major capsid protein VP1, and
      minor capsid proteins VP2 and VP3 in an appropriate ratio. However, the
      regulatory mechanisms of gene expression for the capsid proteins, their nuclear
      transport, and formation of viral inclusions are not well understood. We have
      recently clarified the following regarding the mechanism underlying JCV virion
      assembly; (i) major and minor capsid proteins are synthesized from messenger
      RNAs, the expression ratio of which is determined by alternative splicing, (ii)
      messenger RNAs for the major and minor capsid proteins are polycistronic, and
      their translation occurs downstream of the regulatory protein, agnoprotein, (iii)
      major and minor capsid proteins are translocated to the nucleus in a cooperative
      manner and accumulate at the dot-shaped intranuclear structures called
      promyelocytic leukemia nuclear bodies (PML-NBs), (iv) efficient viral replication
      can occur at the PML-NBs, where capsid assembly is likely to be associated with
      viral DNA replication. PML-NBs are the sites for expression of important nuclear
      functions for the host cells. The finding that the target of JCV infection is the
      PML-NB may contribute greatly to our understanding of the mechanism underlying
      cellular degeneration, which occurs after the formation of intranuclear viral
      inclusions.

PMID- 17038809
TI  - [Cellular tropism and adaptation of the measles virus].
AB  - Measles virus (MV) is a member of the genus Morbillivirus in the family
      Paramyxoviridae. Clinical isolates of MV use signaling lymphocyte activating
      molecule (SLAM) as a cellular receptor. SLAM is mainly expressed on immune cells
      such as immature thymocytes, activated lymphocytes and mature dendritic cells.
      This distribution of SLAM can account for the lymphotropism of MV. On the other
      hand, laboratory strains of MV use CD46 as an alternative receptor, through amino
      acid change(s) in the receptor binding hemagglutinin protein. Recently, several
      reports imply the existence of the cellular receptor(s) other than SLAM and CD46.
      In this review, we discuss the receptor usage of MV and its adaptation to
      cultured cells.

PMID- 17038810
TI  - [Analysis of the mechanisms of tobamovirus RNA replication].
AB  - The replication of eukaryotic positive-strand RNA virus genomes occurs in
      membrane-bound replication complexes. Currently, little is known about the
      process of replication complex formation and the molecular structure of the
      replication complexes. We are trying to understand how eukaryotic positive-strand
      RNA viruses replicate using tobamoviruses as models. Here, I describe our
      approaches to this end.

PMID- 17038811
TI  - [Host factors that regulate the intercellular dynamics of HIV-1 genome during the
      early phase of infection].
AB  - An interplay or battle between virus and its host has been observed within a
      single cell. Upon an infection with retroviruses including human immunodeficiency
      virus type 1 (HIV-1), the viral genome is subjected to several processes that
      include uncoating, reverse transcription of the viral genomic RNA into a cDNA
      copy, transport of this cDNA into the nucleus, and integration of the cDNA into
      the host chromosome. Antiretroviral restriction factors such as TRIM5 alpha and
      APOBEC3G have been recently identified. In addition, nuclear membrane protect
      host chromosomal DNA against incoming viral genome. For successful retroviral
      infection, viral genome must overcome these cellular barriers to establish
      proviral state, in which viral cDNA was stably integrated into host chromosomal
      DNA. In this review, I would summarize the host factors that regulate the
      intercellular dynamics of HIV-1 genome during the early phase of infection,
      especially focusing on factors interacting with HIV-1 integrase and the
      preintegration complex.

PMID- 17038812
TI  - [Dissemination pathways for poliovirus cells to animals models].
AB  - It is considered there are two main pathways for poliovirus dissemination towards
      the central nervous system in humans. One is the pathway through the blood brain
      barrier. The orally ingested virus invades into the blood circulation, and then
      the virus permeates into the central nervous system through the blood brain
      barrier. The other is the neural pathway. In this pathway, the intramuscularly
      inoculated virus is transported through the axons from the synapse to the cell
      body in the central nervous system. We have developed the oral infection system
      using the mouse models. Moreover, we proposed the possibility that PV is
      transcytosed through the brain capillary epithelia in a specific manner. As for
      the neural pathway, we have proved that PV is endocytosed into CD155 containing
      vesicles and the vesicles are retrogradely transported in the axon of rat primary
      motor neuron. We have also shown that the cytoplasmic dynein takes part in the
      transport.

PMID- 17038813
TI  - [Poliovirus susceptibility in cultured cells--an answer to Enders].
AB  - Poliovirus is the causative agent of poliomyelitis. It replicates efficiently in
      the neurons in the central nervous system and produces severe pathological
      lesions. It cannot replicate well in the non-neural tissues. In spite of this
      strict neurotropism in vivo, however, it can replicate in cells of monolayer
      cultures derived from almost any tissues of primates as Enders and colleagues
      initially shown. It was supposed that cellular changes during the process of
      cultivation were required for acquisition of susceptibility. This question
      remained unsolved for a long time. We have recently shown that cells in culture
      acquire poliovirus susceptibility by loosing rapid and robust interferon response
      that has been normally maintained in tissues in vivo.

PMID- 17038814
TI  - [Seasonal influenza activity in Japan and epidemiological investigation for avian
      influenza].
AB  - We analyzed the seasonal influenza activity in 2004/05 and 2005/06 seasons. In
      2004/05 season, the prevalence of influenza started lately. The arrival of a peak
      of influenzal prevalence was the ninth week, and was late in comparison with an
      average year. The prevalence scale was very large, and the estimation number of
      patients was 17,700,000. Since the start of the 2004/05 season, influenza
      activity has mainly been associated with influenza B viruses. The start of
      prevalence of 2005/06 season was 50th week and was comparatively early. The peak
      of the prevalence was the 4th week, same as an average year. Since the start of
      the 2005/06 season, influenza activity has mainly been associated with influenza
      A/H3 viruses.H5N1 highly pathogenic avian influenza virus have spread through
      Africa and Europe from Asia. For purpose such as inhibition of the outbreak of
      new variant influenza, the prevention of human to human infection and expansion,
      early containment, the public health organization has to do unified
      epidemiological investigation immediately nationwide. By doing epidemiological
      investigation, the prevention of infection expansion, specification of the source
      of infection, assessment of the risk of infection, and early detection of new
      variant influenza virus and containment, are expected.

PMID- 17038815
TI  - [Preparedness and international contribution on H5N1 highly pathogenic avian
      influenza and pandemic-influenza].
AB  - Since the end of 2003, simultaneous outbreaks caused by H5N1 highly pathogenic
      avian influenza viruses (H5N1-HPAIV) occurred in poultries and in wild birds in
      the East Asia. The outbreaks are spreading now at least 48 countries in the
      Middle Eastern, African and European countries in addition to the East Asia.
      During the outbreaks, over 200 human infection cases with 55% fatality are
      confirmed at the moment and some human-to-human transmission in family clusters
      have been observed. The outbreaks are no more out of control and pandemic
      potential caused by H5N1-HPAIV is major concern. Therefore, it is urgently
      necessary to develop new diagnostic kits and effective vaccines and to stockpile
      anti-influenza drugs before pandemic alert period phase 4 defined by WHO.
      Furthermore, international supports to the affected countries for development and
      improvement of diagnostic system are required in the public health aspect.

PMID- 17038816
TI  - [Influenza virus receptors in the human airway].
AB  - Avian influenza A (H5N1) virus infections have resulted in more than 100 human
      deaths; yet, human-to-human transmission is rare. We demonstrated that the
      epithelial cells in the upper respiratory tract of humans mainly possess sialic
      acid linked to galactose by alpha 2,6 linkages (SA alpha 2,6Gal), a molecule
      preferentially recognized by human viruses. However, many cells in the
      respiratory bronchioles and alveoli possess SA alpha 2,3Gal, which is
      preferentially recognized by avian viruses. These facts are consistent with the
      observation that H5N1 viruses can be directly transmitted from birds to humans
      and cause serious lower respiratory tract damage in humans. Furthermore, this
      anatomical difference in receptor prevalence may explain why the spread of H5N1
      viruses among humans is limited. However, since some H5N1 viruses isolated from
      humans recognize human virus receptors, additional changes must be required for
      these viruses to acquire the ability for efficient human-to-human transmission.

PMID- 17038817
TI  - [Accumulation of amino acid substitutions promotes irreversible structural
      changes in the hemagglutinin of human influenza AH3 virus during evolution].
AB  - During protein evolution the amino acid substitutions accumulate with time.
      However, the effect of accumulation of the amino acid substitutions to structural
      changes has not been estimated well. We will propose that the discordance of
      amino acid substitution on the HA protein of influenza A virus is useful for the
      assessment of structural changes during evolution. Discordance value can be
      obtained from the experimental data of tolerance or intolerance by introducing
      site directed mutagenesis at the homologous positions of two HA proteins holding
      the same amino acid residues. The value of discordance correlated to the number
      of amino acid differences among proteins. In the H3HA discordance rate was
      calculated to be 0.45% per one amino acid change. Furthermore, discordance of
      amino acid substitutions suggests that tolerable amino acid substitutions in
      different order have a probability of promoting irreversible divergence of the HA
      protein to different subtypes.

PMID- 17038818
TI  - [Molecular mechanism of replication and transcription of the influenza virus
      genome and host factors].
AB  - The genome of influenza A virus is a set of eight segmented- and single-stranded
      RNAs. A basic transcription and replication unit is the genome complexed with
      viral RNA-dependent RNA polymerases and nucleoprotein (NP). For the efficient
      transcription and replication of the genome, not only viral factors but also host
      cell-derived factors are required. Although receptor and protease molecules play
      important roles in infection and pathogenicity, it is also possible that host
      factors involved in the virus genome function determine these. PB2, for instance,
      is reported to be a possible candidate for determination of the host range of
      avian influenza viruses. Here we summarize recent progresses in the molecular
      mechanism of the influenza virus genome transcription and replication and discuss
      the involvement of host factors in these processes.

PMID- 17038819
TI  - [Diagnosis and Treatment of influenza--clinical investigation on viral shedding
      in children with influenza].
AB  - Children with influenza usually shed viruses from the several days before onset
      of clinical symptoms, and viruses are isolated for one or two weeks after onset.
      Point-of-care rapid diagnostic tests are useful to guide use of antiviral agents,
      appears over 90% sensitivity and specificity for influenza A with nasopharyngeal
      specimens compared with cell culture. The detection limits of these test kits are
      103 pfu or over, so it is necessary to consider viral load in clinical specimens
      for diagnosis with these kits. Viral load are decreased after the start of
      antiviral agents, but influenza viruses are isolated in more than half of
      pediatric patients when fever get down, and resistant viruses are detected in
      some of these patients. It is very important for influenza control to investigate
      on viral shedding and resistant viruses.

PMID- 17038820
TI  - [Properties of the Ebola virus glycoprotein].
AB  - In central and west Africa, Ebola virus, a member of the filovirus group, has
      produced sporadic outbreaks of lethal disease. This virus causes hemorrhagic
      fever in humans and nonhuman primates, resulting in mortality rates of up to 90%.
      Although there are no satisfactory biologic explanations for this extreme
      virulence, it has been suggested that functions of the envelope glycoprotein are
      likely to play important roles in the pathogenicity of Ebola virus.

PMID- 17038821
TI  - Delivering pneumococcal vaccine to a high risk population: the Navajo experience.
AB  - High rates of preventable diseases such as pneumococcal disease occur among the
      Navajo despite their universal health insurance through the Indian Health
      Service. The objective of this study was to determine the proportion of Navajo
      adults vaccinated with pneumococcal polysaccharide vaccine and to examine key
      features of vaccination programs of the Navajo Indian Health Service. For this
      cross-sectional study, medical charts of Navajo patients with vaccine indications
      were randomly selected and reviewed to determine who had been vaccinated as of
      January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95%
      confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine
      indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs
      utilized extensive public health nursing, home visits, standing orders, and
      "express lane" clinics. In spite of excellent delivery systems and universal
      healthcare, the proportion of Navajo persons vaccinated was still below the goals
      for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and
      60% of high-risk persons 18-64 years old vaccinated.

PMID- 17038822
TI  - Physician knowledge and perspectives regarding influenza and influenza
      vaccination.
AB  - BACKGROUND: Recent studies have demonstrated that healthy children younger than
      24 months of age are at risk for influenza-associated hospitalization and
      influenza related complications. In light of this, the American Academy of
      Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) of
      the Centers for Disease Control and Prevention changed their recommendation for
      influenza vaccination for the 2004-05 season to include universal vaccination for
      all healthy children 6-23 months of age. METHODS: A self-administered survey was
      distributed to a random sampling of family practitioners and pediatricians in
      Chicago, IL. Questions were asked regarding demographics, current use of
      influenza vaccines, and knowledge regarding influenza vaccines and influenza
      infection in children. Answers were scored as correct based on published
      literature and AAP/ACIP recommendations. RESULTS: During the 2002-2003 influenza
      season, recommendation for influenza vaccination and perceived use for both
      healthy children and children with a high-risk medical condition were both low.
      The majority of physicians were not aware of the severity of influenza infection
      in young children, could not correctly identify all contraindications to
      receiving vaccination, did not know which children require two vaccinations, and
      were not aware of the complications of influenza in children. CONCLUSIONS: To
      achieve the goal of universal influenza vaccination coverage for the 2004-05
      season for healthy children 6-23 months of age, physicians will need a greater
      understanding of the severity of influenza illness in this age group coupled with
      an increased knowledge of indications for vaccine administration.

PMID- 17038823
TI  - Immunogenicity and tolerability of intradermal administration of an HCV E1-based
      vaccine candidate in healthy volunteers and patients with resolved or ongoing
      chronic HCV infection.
AB  - The tolerability and immunogenicity of intradermal injections of a candidate HCV
      vaccine, based on the E1 protein of the hepatitis C virus (HCV), was examined in
      an exploratory study in healthy volunteers, in subjects with a history of
      resolved HCV infection, and in patients suffering from therapy-resistant chronic
      HCV. Sub-epidermal injection of three doses of 4 microg of non-adjuvanted E1
      vaccine induced much weaker humoral and cellular immune responses in healthy
      subjects and chronic HCV patients than the intramuscular administration of 20
      microg E1 formulated on alum. However, in three subjects who cleared HCV
      infection, intradermal administration of this low dose of E1 induced rapid and
      clear anamnestic responses. These data demonstrate that E1-specific immune
      responses can be induced in resolving HCV infections and that memory (B and T)
      cells can be restimulated with suboptimal doses of E1 antigen.

PMID- 17038824
TI  - Mechanism of adsorption of three recombinant Streptococcus pneumoniae (Sp)
      vaccine antigens by an aluminum adjuvant.
AB  - The adsorption of three Streptococcus pneumoniae (Sp) vaccine antigens by
      aluminum-containing adjuvants was studied. The antigens showed high binding
      affinity isotherms with aluminum hydroxide adjuvant described by the Langmuir
      equation but virtually no binding to aluminum phosphate adjuvant. The effects of
      ionic strength and ethylene glycol were evaluated to determine whether
      electrostatic or hydrophobic interactions were responsible for the observed
      binding to aluminum hydroxide, but no significant change in the adsorptive
      capacity was observed at either high ionic strength nor high concentrations of
      ethylene glycol for any of the antigens. This indicates that neither
      electrostatic nor hydrophobic interactions appear to be responsible for the
      observed binding, which means that ligand exchange may be the primary mechanism
      for this interaction. Further studies to evaluate the ability to elute a Sp
      antigen from aluminum hydroxide using fibrinogen (adsorptive coefficient 2.2
      mL/microg) as a competitive protein resulted in evidence that Sp antigen follows
      the trend that proteins with higher adsorptive coefficients are able to displace
      those with lower adsorptive coefficients. It was also noted that the Sp antigens
      and alpha-lactalbumin (adsorptive coefficient 1.8 mL/microg) have similar
      adsorptive coefficients indicative of high affinity binding isotherms but do not
      contain phosphate, which has previously been used to explain ligand exchange for
      such proteins as alpha-casein and hepatitis B surface antigen (HBsAg). Further
      investigations using alpha-lactalbumin as a model protein may elucidate the
      binding interaction between the antigens in this study and aluminum adjuvants.

PMID- 17038825
TI  - Safety concerns regarding combination vaccines. Perspective of select European
      countries.
AB  - This study explored health officials' perception of parental concern regarding
      the safety of combination vaccines and its impact on policy decisions in
      different European countries. Interviews were conducted with governmental and
      nongovernmental health officials in the United Kingdom, France, Ireland and
      Sweden over a four-month period. Parental concern regarding the safety of
      combination vaccines was perceived to be prevalent in the United Kingdom, Ireland
      and Sweden while no such concern was evident in France. The concern was limited
      to the combined measles, mumps and rubella vaccine and its alleged causal
      association with autism and did not carry over to other combined vaccines.
      Although proposed by certain political groups, no policy changes regarding
      combination vaccines were made in any study country.

PMID- 17038826
TI  - A non-living nasal influenza vaccine can induce major humoral and cellular immune
      responses in humans without the need for adjuvants.
AB  - Twenty-eight healthy adult volunteers were immunized intranasally with an
      inactivated whole-virus influenza vaccine based on the strain A/New
      Caledonia/20/99 (H1N1), either in saline or mixed with formaldehyde-inactivated
      Bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with
      mucoadhesive properties. After four doses, all groups of vaccinees developed
      significant IgG- and IgA-antibody responses, measured by ELISA, in respectively
      serum and nasal secretions. None of the volunteers had demonstrable
      hemagglutination inhibition (HAI) antibodies in serum before being immunized,
      whereas more than 80% of them reached HAI titers>or=40, considered protective,
      after immunizations. In addition, cellular immune responses, measured as
      significant increases in CD4+ T-cell proliferation and granzyme B-producing
      cytotoxic T-cells, were detected against the vaccine strain as well as against
      heterologous virus strains (H3N2). However, no additive effect on these responses
      could be demonstrated with use of B. pertussis or the thixotropic substance in
      the present vaccines. It appeared, actually, that the mucoadhesive vehicle
      containing the thixotropic substance was less efficient than were the two other
      formulations. An influenza vaccine made as a simple particulate formulation of
      inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an
      attractive alternative to currently available vaccines.

PMID- 17038828
TI  - A meta-analysis of studies comparing the respiratory route with the subcutaneous
      route of measles vaccine administration.
AB  - The respiratory tract has been suggested as an optimal alternative site to target
      measles vaccine delivery. We performed a meta-analysis to evaluate the efficacy
      of measles vaccine administered through the respiratory route compared to the
      subcutaneous route. We analyzed 20 reported results from 16 eligible studies.
      Seroresponse was 4% higher amongst vaccinees in the respiratory group compared to
      the subcutaneous group (M-H pooled RR = 1.04; 95% CI = 0.98-1.10). For vaccinees
      over 9 months of age, seroresponse was 15% higher in the respiratory group (M-H
      pooled RR = 1.15; 95% CI = 1.08 to 1.17). When Edmonston Zagreb (EZ) strain was
      used, the vaccine was found to be neither more nor less efficacious when
      administered through respiratory route (M-H pooled RR=1.00; 95% CI = 0.94 to
      1.08). Seroresponse in the vaccinees receiving aerosol measles vaccine was 10%
      higher (M-H pooled RR = 1.10, 95% CI = 1.04-1.17) compared to those who received
      measles vaccine through the subcutaneous route. Seroresponse due to aerosolized
      EZ vaccine was 9% higher than subcutaneous EZ vaccine (M-H pooled RR = 1.09; 95%
      CI = 1.02-1.16). The seroresponse among seropositive vaccinees was 60% higher (M
      H RR = 1.60; 95% CI = 1.40 to 1.80). The results suggest that the respiratory
      route of delivery of measles vaccine is at least as efficacious as measles
      vaccine administered through the subcutaneous route. However, more research is
      required on standardization of dosage, administration equipments, efficacy, and
      safety of respiratory (aerosol) route of administration of measles vaccine.

PMID- 17038827
TI  - Phase I, randomized, controlled trial to study the reactogenicity and
      immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in
      healthy adults.
AB  - We performed a randomized, placebo-controlled, dose-escalating clinical trial to
      evaluate the safety and immunogenicity of an inactivated, split virion,
      trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as
      carriers. A total of 64 adults (mean age 29; range 19-69 years) were randomly
      allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5,
      15, or 30 microg hemagglutinin antigen of each of the three influenza strains
      (A/Johannesburg/82/96 [H1N1], A/Nanchang/933/95 [H3N2], B/Harbin/07/94) or
      placebo via nasal spray on two occasions separated by 28 days. Adverse events
      were assessed immediately after immunization and for 14 days after each dose.
      Nasal and serum antibodies were measured before and two weeks after each dose.
      All but three participants completed the study; no withdrawals were because of
      adverse events. Adverse events were similar immediately after immunization except
      for anterior nasal dripping after the first dose which was more common in the
      combined vaccine groups (64.4%) than in the placebo group (31.3%; p < 0.05). A
      similar trend was observed after the second dose. Nasal dripping was also more
      common in the first two days after immunization in the vaccine groups than the
      placebo group (31.3%-50% vs. 0%) with no difference with increasing vaccine dose.
      The vaccine elicited a modest serum antibody response against all three viruses,
      with the highest dose eliciting the highest serum antibody levels. In contrast,
      significant nasal antibody rises were observed for all three viruses; again, the
      30 microg group achieved the highest mucosal antibody levels at the earliest time
      points. We conclude that this trivalent, split virion, inactivated nasal
      influenza vaccine formulated with lipid/polysaccharide molecule carriers is well
      tolerated and modestly immunogenic in healthy adults.

PMID- 17038829
TI  - Exercise-induced serum enzyme elevations confounding the evaluation of
      investigational drug toxicity. Report of two cases in a vaccine trial.
AB  - Two subjects developed marked elevations in creatine kinase and other serum
      enzymes associated with mild myalgia during a randomized, double-blind,
      controlled Phase 1 clinical trial of an investigational live, attenuated vaccine
      against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax
      WN02 while the other subject was enrolled in an active control group and received
      licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was
      interrupted, and an investigation was begun to evaluate the enzyme abnormalities.
      As daily serum samples were collected for determination of quantitative viremia,
      it was possible to define the enzyme elevations with precision and to relate
      these elevations to physical activity of the subjects, symptoms, and virological
      and serological measurements. Evaluation of both subjects clearly showed that
      skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible
      for the biochemical abnormalities. This investigation also implicated strenuous
      exercise as the cause of the apparent muscle injury rather than the study
      vaccines. As a result of this experience, subjects engaged in future early-stage
      trials of these live, attenuated viral vaccines will be advised not to engage in
      contact sports or new or enhanced exercise regimens for which they are not
      trained or conditioned. The inclusion of placebo control arm (in lieu of or
      addition to an active vaccine control) will also be useful in differentiating
      causally related serum enzyme elevations.

PMID- 17038830
TI  - Role of neutralizing antibodies in protective immunity against HIV.
AB  - HIV continues to be a major health problem world wide, however the situation is
      particularly serious in Asian and Sub-Saharan countries. Therefore, development
      of an effective HIV vaccine could help to reduce the severity of the disease and
      prevent infection. Over the last two decades significant efforts have been made
      towards inducing potent humoral and cellular immune responses by vaccination,
      however antibodies and CTL responses alone are likely not sufficient for inducing
      sterilizing immunity or long-term control of viral replication. Therefore, it is
      generally believed that both humoral and cellular responses will be needed for an
      effective HIV vaccine. In support of humoral immunity, monoclonal antibodies that
      recognize critical neutralizing epitopes have shown to be effective at passive
      transfer experiments in conferring protection against challenge infection.
      However, antibodies to similar epitope specificities are difficult to induce by
      vaccination. Therefore, optimization of Env structure is needed for exposing
      appropriate neutralizing epitopes and masking non-neutralizing epitopes. Since
      the crystal structure of the core of Env glycoprotein has been solved, efforts
      are in progress to design novel Env immunogens that may induce effective
      neutralizing responses. Furthermore, there are HIV-1 strains that are resistant
      to neutralization by monoclonal antibodies, yet neutralized by pooled sera from
      HIV-1 patients. Therefore, efforts should be made to identify these novel
      epitopes and to design strategies to incorporate them in potential vaccines. To
      facilitate comparative evaluation of vaccine immunogens for their ability to
      induce cross clade neutralizing antibodies, efforts should be made to use
      standardized neutralization assays and standard virus panels. Once potent HIV Env
      structure have been identified, their effectiveness may be enhanced through the
      use of adjuvants, delivery systems and prime and boost strategies to improve the
      quality and magnitude of neutralizing responses.

PMID- 17038831
TI  - Characterization of the protein content of a meningococcal outer membrane vesicle
      vaccine by polyacrylamide gel electrophoresis and mass spectrometry.
AB  - The development and evaluation of outer membrane vesicles as vaccines against
      meningococcal disease has been carried out for more than two decades. Although
      such vaccines have limitations and are not widely licensed, they continue to be
      used to disrupt clonal outbreaks caused by group B meningococci and a wealth of
      information is now available from large-scale clinical studies. One dimensional
      polyacrylamide gel electrophoresis and semi-quantitative measurement of the major
      proteins is one method used to evaluate and control these products. However, it
      is often difficult to determine exactly which bands on a one dimensional gel
      correspond to the key antigens whose presence must be demonstrated for control
      and lot release. We have therefore carried out mass spectrometric analyses of
      outer membrane vesicle vaccine samples to definitively identify the bands
      containing seven key antigens: Omp85, FetA, PorA, PorB, RmpM, OpcA and NspA. An
      additional 33 proteins present in the vaccine were also identified and this
      information will be useful both for future quality control and for the
      interpretation of data from vaccine trials.

PMID- 17038832
TI  - Medical burden of respiratory syncytial virus and parainfluenza virus type 3
      infection among US children. Implications for design of vaccine trials.
AB  - Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are two
      leading causes of lower respiratory illness (LRI) in infants. Many efforts have
      been directed to develop vaccines against these two viruses. Licensure of new
      vaccines includes three phases of clinical trials to evaluate safety,
      immunogenicity, and efficacy. To design an efficacy trial, age-specific incidence
      rates of suitable clinical endpoints need to be available. In this review,
      historical data are summarized to estimate the age-specific rates of acute
      respiratory illness (ARI), LRI, and hospitalization caused by RSV and PIV3 among
      US children <5 years of age. Nation-wide data are available for hospitalization
      but not ARI and LRI. Age-specific rates of RSV and PIV3-related ARI or LRI can
      vary 9-fold or 5-fold, respectively, in different studies conducted in different
      populations using different clinical and laboratory definitions. The annual
      medical burden for RSV and PIV3 in children <5 was estimated respectively to be
      about 4.19 and 3.24 million cases of medically-attended ARI, 2.1 and 1.08 million
      cases of LRI, and 113 and 29 thousand cases of hospitalization, respectively. The
      impact of three important variables including age at vaccination, clinical
      endpoints, and laboratory diagnosis in designing efficacy trials is discussed. A
      RSV vaccine which is safe and effective in the first six months of life is
      optimal to reduce the severe disease burden of LRI and hospitalization, however,
      interference of maternal antibody may reduce vaccine efficacy in this age group.
      LRI occurs more frequently than hospitalization and may be the most feasible
      clinical endpoint for designing efficacy trials. Since age-specific rates of RSV
      and PIV3-related LRI can vary significantly in different populations, collecting
      age-specific LRI rates in phase 1 and 2 trials to further understand this
      variability appears warranted.

PMID- 17038833
TI  - Free-riding, fairness and the rights of minority groups in exemption from
      mandatory childhood vaccination.
AB  - The authority of government to require participation in mandatory childhood
      vaccination programs may not target specific groups for either participation or
      exemption on a discriminatory basis. This poses difficulties when allowing
      religious or philosophical exemptions to mandatory vaccination, because certain
      groups are more likely to appeal for exemption. Avoiding loss of herd immunity,
      then, may require either discrimination against these groups by disallowing an
      exemption option that is available to others, or by denying the good of an
      exemption option to the entire population because of the action of certain
      groups. To avoid this unacceptable choice, steps must be taken now to more
      stringently enforce exemption requirements.

PMID- 17038834
TI  - A DNA-based vaccine for the prevention of human cytomegalovirus-associated
      diseases.
AB  - Multiple lines of evidence indicate that in the transplant population human
      cytomegalovirus (HCMV) infection and its associated diseases are controlled by
      humoral and cellular immune responses similar to those that arise in
      asymptomatic, healthy individuals during a naturally-acquired infection. The
      dominant antibody response to HCMV is to the major surface glycoprotein B (gB)
      and the dominant cellular immune response is to the tegument phosphoprotein
      (pp65). We propose that an immunotherapeutic plasmid DNA (pDNA) vaccination
      approach that induces the requisite responses to major immunological targets of
      HCMV may provide relief from HCMV-associated diseases in the transplant setting.
      We have developed gene-based immunotherapeutic products consisting of pDNAs
      encoding gB and pp65 of HCMV. When tested individually in mice, both pDNAs were
      highly immunogenic. Relative to vaccination with either gB or pp65 pDNA delivered
      alone, vaccination with gB and pp65 pDNAs delivered together in phosphate
      buffered saline (PBS) elicited reduced antibody and T cell responses to each
      antigen. Formulating this bivalent vaccine with a poloxamer-based delivery system
      (VF-P1205-02A), however, significantly increased the antigen-specific immune
      responses relative to those induced with the bivalent vaccine in PBS, and
      completely abrogated the decrease in pp65-specific T cell responses observed in
      mice covaccinated with the pDNAs in PBS. Based on these data, and a favorable
      safety and toxicity profile in preclinical studies, the bivalent HCMV vaccine
      consisting of gB and pp65 pDNAs delivered with VF-P1205-02A has advanced to human
      clinical trials.

PMID- 17038836
TI  - Colorectal cancer prevention and screening: a Health Belief Model-based research
      study to increase disease awareness.
AB  - The purpose of this quasi-experimental study was to evaluate the effects of a
      Health Belief Model-based colorectal cancer (CRC) education session on adult
      participants. Education sessions were conducted at a site chosen by the
      participants, such as their homes, in a mid-sized, mid-Western city. Thirty-one
      Caucasian adults participated. Eleven were men (35%) and 20 were women (65%).
      Study results reveal that the education sessions were an effective way to promote
      awareness of CRC prevention and screening. The participants' responses reflected
      a positive and significant (p < .0001) improvement in all areas except beliefs
      regarding maintenance of a healthy weight (p = .0574). The greatest effect was on
      men, current smokers, and those with a high school education or less. Education
      sessions were equally effective for auditory and visual learners. The 31
      participants planned to share the information with at least 32 other individuals.
      The participants acquired an increased awareness of CRC prevention and screening.
      Willingness to discuss CRC after the education sessions may be significant,
      especially because the others may, in turn, share the information. Nurses need to
      be aware of CRC screening guidelines. The impact of patient teaching on this
      health promotion effort may reach beyond the patients who were in contact with
      the nurses. Public awareness might be further increased when patients share this
      information with others.

PMID- 17038837
TI  - Physicians, nonphysician healthcare providers, and patients communicating in
      hepatitis C: an in-office sociolinguistic study.
AB  - In-office conversations about hepatitis C can impact patients' perceptions of
      outcomes, as well as medication adherence. This study analyzed interactions
      between physicians, nonphysician healthcare providers (including nurses), and
      patients with hepatitis C virus infection in order to examine differences based
      on number and type of providers participating. Gastroenterologists, nonphysician
      healthcare providers, and patients with hepatitis C virus infection were video-
      and audio-recorded during regularly scheduled visits. Recordings were transcribed
      and analyzed using validated sociolinguistic techniques. Thirty-four visits took
      place with a physician only, 4 with a nonphysician healthcare provider only, and
      25 with both providers (9 concurrent and 16 consecutive). Differences among the
      participant schema included visit length, patient "talk-time," and motivation
      provided. When providers saw patients consecutively, differing information was
      sometimes provided. In visits where providers saw the patient concurrently,
      competing authority between providers and exclusion of the patient through use of
      medical jargon were obstacles to ideal communication. Differences in hepatitis C
      related interactions based on the number and type of participants suggest
      opportunities for improved communication. In visits with multiple providers,
      physicians and nurses should attempt to ensure that they (a) avoid supplying
      differing information, (b) present a "unified front" to avoid competing
      authority, and (c) minimize the use of medical jargon, which excludes patients
      from participating in their own healthcare.

PMID- 17038838
TI  - Nurse-administered propofol sedation: a review of current evidence.
AB  - This article highlights a highly controversial practice issue referred to as
      nurse-administered propofol sedation, which affects registered nurses as well as
      advanced practice nurses in many different practice settings across the United
      States. Amid varied advice from professional organizations and state licensing
      boards, a thorough and systematic review of the current evidence provides insight
      into the question of safety associated with the practice. The evidence examined
      includes position statements from professional organizations and state boards,
      information from the United States Food and Drug Administration and the Joint
      Commission on Accreditation of Healthcare Organizations, and published research
      since 1999. The body of evidence demonstrates diverse positions; however, the
      empirical evidence in the author's opinion unanimously supports nurse
      administered propofol sedation as a safe practice in nonintubated adult patients.
      Under research conditions, participants had a low incidence of untoward events
      and were adequately rescued with no intubations required and no deaths reported.

PMID- 17038840
TI  - Clinical applications of argon plasma coagulation in endoscopy.
AB  - The argon plasma coagulator is a device used for noncontact thermal coagulation
      of tissue. The device was first used in open and laparoscopic surgical procedures
      and in 1991 was adapted for use in endoscopy. Since then, argon plasma
      coagulation has expanded its clinical applications in the treatment of various
      gastrointestinal conditions. The endoscopy nurse plays an important role in the
      care of patients before, during, and after argon plasma coagulation treatment.
      This article reviews the principles and components of the argon plasma
      coagulator, and provides a summary of the various clinical applications, patient
      safety practices, and potential complications of argon plasma coagulation
      therapy.

PMID- 17038842
TI  - Reprocessing of endoscopic accessories and valves.

PMID- 17038843
TI  - Reprocessing of water bottles used during endoscopy.

PMID- 17038844
TI  - A photodynamic therapy for ampullary cancer.
AB  - This case study describes the application of photodynamic therapy for palliative
      care in an older patient with inoperable pancreatic cancer. For this procedure, a
      photosensitizing drug is applied endoscopically followed by a laser light beam
      that is directed onto the tumor, facilitating a photochemical reaction. The
      photodynamic drug becomes cytotoxic in this process, working to destroy the
      neoplastic tissue. In this case study, the procedure was performed by an
      endoscopic surgeon in the operating room at a large Midwestern academic medical
      center. The details of application of photodynamic laser therapy, which
      frequently alleviates discomfort for patients who otherwise have few options, is
      described for this patient.

PMID- 17038845
TI  - Herbs, supplements, and nonprescribed drugs.

PMID- 17038846
TI  - Ergonomics for the endoscope.

PMID- 17038847
TI  - An update on advanced/specialist roles in ireland.

PMID- 17038848
TI  - Trading places.

PMID- 17038849
TI  - Larry's story.

PMID- 17038852
TI  - A word to the wise: tips for the first-time traveler.

PMID- 17038853
TI  - How OTs and PTs can help stroke patients recover.

PMID- 17038855
TI  - Integrating Iyengar yoga into rehab for spinal cord injury.

PMID- 17038868
TI  - Sirolimus--challenging current perspectives.
AB  - Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It
      inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of
      various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a
      maintenance immunosuppressive agent in organ transplantation. Also, a potentially
      benefit of this valuable drug in some immunologic and malignant diseases is
      currently under scrutiny.Classical side effects: hematological (anaemia,
      leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity
      oedema and impaired wound healing have been frequently associated with the use of
      sirolimus. Additionally with its increased use, transplant professionals are
      encountering a variety of previously unreported and potentially more severe side
      effects.Here, we review the most recent data on sirolimus unexpected side effects
      (with an emphasis on pulmonary and renal toxicity), its use in renal
      transplantation and its new potential therapeutic indications (chronic
      glomerulopathies, polycystic kidney disease, different types of cancer). A brief
      description of the current knowledge of sirolimus therapeutic drug monitoring,
      methods of analysis, pharmacokinetics and drug interactions with calcineurin
      inhibitors is also included.

PMID- 17038869
TI  - TDM grand rounds: neonatal nicotine withdrawal syndrome in an infant prenatally
      and postnatally exposed to heavy cigarette smoke.
AB  - A heavy smoking, lactating mother delivered a baby that exhibited spontaneous
      tremors, fluctuations of muscular rigidity, and opisthotonus at 48 hours of life.
      Although the symptoms did not disappear within the following days, they could be
      controlled by swaddling or wrapping the baby in a blanket. The absence of any
      other etiology generated a suspicion of prenatal exposure to heavy tobacco smoke
      and potential neonatal nicotine withdrawal syndrome. This diagnosis was supported
      by extremely high concentration of hair nicotine and cotinine in the infant's
      hair and in different segments of maternal hair. The presence of non-negligible
      amounts of nicotine and cotinine in breast milk confirmed that the mother did not
      quit smoking after delivery, despite her reports. The breast-fed newborn
      continued to have 3 to 4 crises of spontaneous tremors and alternant muscular
      rigidity per day for a month. More studies are needed to establish neonatal
      nicotine withdrawal.

PMID- 17038870
TI  - The use of TDM data to assess the validity of defined daily doses of
      antiepileptics: a comparison between a Czech and Swedish University Hospital.
AB  - Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were
      recorded for drugs used in monotherapy or in combination therapy in the
      University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma
      concentrations were used as an indicator of the quality of treatment. PDDs were
      compared with the defined daily doses (DDDs) suggested by WHO in the ATC/DDD
      index 2005. Request and reply forms for therapeutic drug monitoring (TDM) were
      used as a source of mean PDDs. The study included 2,824 adult out- and in
      patients in Huddinge treated from 1995 to 1999 and 1,268 out-patients treated in
      Ostrava from 1993 to 2004. The differences in PDD were tested by Student's t
      test. Mean values of PDD were used when patients were examined more than once.
      Doses given in mono- and polytherapy were compared. Mean PDDs (in mg) in mono
      /polytherapy in Huddinge and Ostrava were as follows (DDDs in parenthesis):
      carbamazepine 588/842 and 618/770 (1,000), clonazepam 3.0/2.5 and 3.4/2.4 (8),
      phenytoin 278/314 and 291/288 (300), gabapentin -/1,533 and -/921 (1,800),
      lamotrigine 228/228 and 216/195 (300), phenobarbital 90/75 and 183/117 (100),
      vigabatrin -/1,794 and -/1,259 (2,000), valproic acid 1,139/1,476 and 814/950
      (1,500). The PDDs of most of the AEDs were lower than the DDDs with the
      exceptions for valproic acid (Huddinge, in polytherapy only), phenytoin, for
      which PDDs and DDDs were very close, and phenobarbital for which they were
      similar in Huddinge but higher in Ostrava. PDDs in monotherapy were only slightly
      lower than in combination therapy. Patients with plasma concentrations within the
      therapeutic range were usually treated with slightly higher doses than the
      remainder. In general, plasma concentrations tended to be in the low therapeutic
      range. The differences in PDDs between hospitals were significant in the case of
      valproic acid (P < 0.001), phenobarbital (except monotherapy within), vigabatrin,
      and gabapentin (P < 0.01), and carbamazepine (in monotherapy P < 0.05,
      polytherapy P < 0.01). Our data suggest that the DDDs of AEDs should be
      reconsidered as, in the majority of cases, they appear to be too high.

PMID- 17038871
TI  - Therapeutic monitoring of antiepileptic drugs: a comparison between a Czech and a
      Swedish University Hospital.
AB  - Plasma concentrations obtained during routine therapeutic monitoring of
      antiepileptic drugs (AED) (N03A ATC group) were compared in patients treated with
      one or several AED in the University Hospitals in Ostrava, Czech Republic and
      Huddinge, Sweden. Request and reply forms for therapeutic drug monitoring (TDM)
      were used as a source of mean plasma concentrations (PC). The study included
      2,824 adult out- and inpatients in Huddinge treated from 1995 to 1999 and 1,268
      outpatients treated in Ostrava from 1993 to 2004. PC of valproic acid in Huddinge
      and all AED except clonazepam in Ostrava were analyzed with gas-liquid
      chromatography. Plasma concentrations of clonazepam in Ostrava and all AED except
      valproic acid in Huddinge were analyzed by HPLC. The differences in PC were
      tested by Student's t-test. Chi(2) method was used for the differences in the
      distribution of PC relative to the therapeutic window. The mean plasma
      concentrations generally reached the apparent therapeutic ranges but were below
      the range in the cases of phenytoin monotherapy in both hospitals, and
      clonazepam, phenobarbital and phenytoin in polytherapy in Ostrava. In monotherapy
      33% of the analyses showed sub-therapeutic concentrations in Huddinge, compared
      to 38% in Ostrava. Eight percent of the analyses showed potentially toxic
      concentrations in Huddinge, but only 3% in Ostrava. The highest number of sub
      therapeutic concentrations was detected for phenytoin in both hospitals: 59% in
      Huddinge, 78% in Ostrava. In polytherapy only slight differences between the
      hospitals were found. PC/dose ratios were significantly lower in polytherapy than
      in monotherapy for carbamazepine and valproic acid in both hospitals. In contrast
      a higher PC/dose ratio was found in polytherapy for phenytoin in both cohorts and
      for lamotrigine in Ostrava. Drug treatment of epilepsy in our two hospitals is
      surprisingly similar in terms of achieved plasma concentrations, in spite of
      socioeconomic and cultural differences between our two countries. This may be
      explained by the long experience with TDM in both hospitals, which has the
      inherent capacity to promote evidence based drug therapy.

PMID- 17038872
TI  - Effect of adjunctive lamotrigine treatment on the plasma concentrations of
      clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar
      disorder.
AB  - The effect of lamotrigine on the steady-state plasma concentrations of the
      atypical antipsychotics clozapine, olanzapine, and risperidone was investigated
      in patients with schizophrenia or bipolar disorder stabilized on chronic
      treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n =
      10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final
      dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at
      baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and
      200 mg/day respectively. The plasma concentrations of clozapine, norclozapine,
      risperidone, and 9-hydroxy-risperidone did not change significantly during
      treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31
      +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10,
      the difference between week 10 and baseline being statistically significant (P <
      0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These
      findings indicate that lamotrigine, at the dosages recommended for use as a mood
      stabilizer, does not affect the plasma levels of clozapine, risperidone, and
      their active metabolites. The modest elevation in plasma olanzapine
      concentration, possibly due to inhibition of UGT1A4-mediated olanzapine
      glucuronidation, is unlikely to be of clinical significance.

PMID- 17038873
TI  - Determination of lamotrigine and its metabolites in human plasma by liquid
      chromatography-mass spectrometry.
AB  - A method based on electrospray ionization liquid chromatography-mass spectrometry
      was developed for the quantitative determination of lamotrigine and three of its
      reported metabolites, lamotrigine-2-N-glucuronide, lamotrigine-2-N-methyl, and
      lamotrigine-2-N-oxide in human blood plasma. The method utilized sample
      preparation by precipitation of proteins with acetonitrile, chromatographic
      separation on a reversed-phase system by gradient elution, and monitoring of the
      protonated molecular ions. Two internal standards, 3,5-diamino-6-(2
      methoxyphenyl)-1,2,4-triazine and morphine-3-glucuronide-D3, were utilized to
      achieve precise quantification. The method validation comprised a demonstration
      of an agreement in the quantification of lamotrigine with that of a routine HPLC
      UV method. The limits of detection were between 0.05 and 0.16 micromol/L. The
      method was employed for the measurement of clinical samples collected from 55
      patients in steady-state prior to the dose intake (trough level). Lamotrigine and
      the 2-N-glucuronide were typically detected, while the N-methyl and N-oxide
      metabolites were detected only rarely. The median lamotrigine plasma level was
      24.0 micromol/L (range, 4.3 to 64 micromol/L), the median 2-N-glucuronide level
      was 2.4 micromol/L (range, <0.05 to 24 micromol/L), and the median lamotrigine 2
      N-glucuronide/lamotrigine ratio was 0.11 (range, <0.01 to 0.64). In conclusion,
      this liquid chromatographic-mass spectrometric method is suitable for
      simultaneous determination of lamotrigine and its metabolites in human plasma.

PMID- 17038874
TI  - Determination of inosine monophosphate dehydrogenase activity in human CD4+ cells
      isolated from whole blood during mycophenolic acid therapy.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is an established target in
      immunosuppression following organ transplantation. In lymphocytes, reversible
      inhibition of this enzyme by mycophenolic acid (MPA) results in reduced
      production of guanine and deoxyguanine nucleotides and thereby retarded
      proliferation of activated cells. In order to examine MPA pharmacodynamics in
      renal allograft recipients, the authors have developed an assay for the
      determination of IMPDH activity in CD4+ cells directly isolated from a small
      blood volume. Paramagnetic beads coated with anti-CD4 antibodies were utilized
      for the cell isolation. The intracellular MPA concentration was restored by
      incubating the cells in microfiltrated plasma from the original sample. Inosine
      5'-monophosphate (IMP; substrate) and nicotine adenine dinucleotide (NAD; co
      factor) were added to cell lysates, and IMPDH activity was quantified as the
      xanthosine 5'-monophosphate (XMP) production rate (pmol/10 cells/min) determined
      by liquid chromatography after hydrolytic cleavage to xanthine. The reaction
      kinetics were saturated with IMP and NAD concentrations of 1.79 micromol/L and
      0.38 micromol/L, respectively. The production rate was linear in the interval
      0.13 to 8.7 pmol XMP/min. Total interseries CVs based on seven replicates at each
      MPA concentration 0, 2.2, and 8.6 microg/mL were 25%, 16%, and 13%, respectively.
      When a single 1 gram mycophenolate mofetil dose was administered to a healthy
      individual, the measured IMPDH activity was 13% of predose value at the MPA peak
      concentration. The present assay allows reliable determination of IMPDH activity
      in CD4+ cells during MPA exposure, reducing the potential influence of sample
      preparation on the measured enzyme activity to a minimum. The assay may be
      applied to assess MPA pharmacodynamics during immunosuppressive treatment,
      maintaining the influence of intracellular MPA on the IMPDH activity.

PMID- 17038875
TI  - Apparent clearance of sirolimus in heart transplant recipients: impact of primary
      diagnosis and serum lipids.
AB  - The study was aimed to identify factors affecting sirolimus apparent clearance
      (CL/F) in de novo heart transplant recipients using a population pharmacokinetic
      approach. A total of 31 patients (7 female and 24 male) originally included in a
      formal clinical trial, contributed 524 sirolimus blood concentrations with the
      time after dose ranging from 11.08 to 31.83 hours. Sirolimus concentrations were
      measured using liquid chromatography-tandem mass spectrometry and data analysis
      was carried out using NONMEM (Globomax LLC, Hanover, MD) software. Factors
      screened included age, weight, gender, primary diagnosis, biochemical and
      hematological indices, cyclosporine dose, days post-transplant and potential
      interacting medications. The predictive performance of the final model was
      evaluated using a data-splitting method. Sirolimus apparent clearance (CL/F) was
      decreased by 20.8% for every 100-mg increase in cyclosporine daily dose and was
      62.1% lower in patients with primary diagnosis of ischemic heart disease (IHD).
      Sirolimus apparent clearance was 37.8% lower when triglyceride was greater than 2
      mmol/L. Based on the final model, the average values for sirolimus CL/F and
      apparent volume of distribution were 7.09 and 1,350 L/h, respectively. Inter
      subject variability in CL/F was 27.5% and residual random error was 24.1%. This
      study identified cyclosporine dose, hypertriglyceridemia and primary diagnosis of
      IHD as the most important factors affecting sirolimus CL/F. This information may
      assist in dose individualization of sirolimus in transplant recipients.

PMID- 17038876
TI  - Validation of an abbreviated pharmacokinetic profile for the estimation of
      mycophenolic acid exposure in pediatric renal transplant recipients.
AB  - The pharmacokinetics of mycophenolic acid (MPA), the active moiety of the
      immunosuppressant mycophenolate mofetil (MMF), exhibits large inter-individual
      variability. Concentration-controlled dosing of MMF based on therapeutic drug
      monitoring may therefore be advantageous compared to a fixed-dose regimen.
      Because full AUC(0-12) monitoring is not practical and predose MPA concentrations
      correlate only moderately with the corresponding AUC(0-12), the estimation of MPA
      exposure by a limited sampling strategy has been suggested. However, before such
      an algorithm is transferred to clinical practice, it is compulsory to
      prospectively validate it in a different data set, in order to avoid biased
      results. The aim of this investigation was therefore to prospectively validate an
      algorithm based on an abbreviated pharmacokinetic (PK) profile for the estimation
      of MPA exposure in 54 pediatric renal transplant recipients (169 PK profiles) on
      MMF in conjunction with CsA and prednisone on a second data set in a different
      group of patients with a similar immunosuppressive regimen (25 patients, 119 PK
      profiles). An algorithm based on three PK sampling timepoints during the first 2
      hours after MMF dosing (estimated AUC(0-12) = 18.6 + 4.3 x C(0) + 0.54 x C(0.5) +
      2.15 x C(2)) was able to predict the corresponding MPA-AUC(0-12) with a low
      percentage prediction error (10.7%) and an acceptable coefficient of
      determination (r = 0.76). The performance of this algorithm was comparable among
      different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC(0
      12) based on this algorithm was able to differentiate between rejecters and non
      rejecters with a comparable prognostic sensitivity (66.7%) and specificity
      (61.9%) as the full-time MPA-AUC(0-12). In conclusion, the use of this validated
      algorithm for the estimation of MPA exposure based on a limited sampling strategy
      during the first 2 hours after MMF dosing has the potential to optimize MMF
      therapy in pediatric renal transplant recipients.

PMID- 17038877
TI  - CEDIA mycophenolic acid assay compared with HPLC-UV in specimens from transplant
      recipients.
AB  - Routine monitoring of mycophenolic acid (MPA) has been accepted as an essential
      tool in the management of this therapy in transplant recipients. The availability
      of simple, sensitive assays that measure MPA in plasma permits individualization
      of dosing regimens according to pharmacokinetic principles. We report the results
      of an evaluation of the CEDIA Mycophenolic Acid Immunoassay (Microgenics
      Corporation, Fremont, California) for the measurement of plasma MPA
      concentrations in a range of transplant indications and compare its performance
      and specificity to an established HPLC/UV method. Precision and accuracy were
      determined both within and between runs using the quality control materials
      provided with the CEDIA MPA assay, which produced within run (n = 21)
      coefficients of variation (CV%) and biases of less than 5%. The between run
      analyses, performed over consecutive days following daily calibration of the
      assay, showed CVs and biases of less than 7%. Routine patient samples (n = 298)
      from 142 patients of varying transplant type were analyzed using the CEDIA MPA
      kit and HPLC/UV methods. Regression analysis of the patient samples gave an
      equation of CEDIA = 1.18 HPLC/UV + 0.45 (r = 0.83). According to the
      manufacturer's product information, there is 192% cross reactivity with the
      active mycophenolate acyl glucuronide. The data presented suggest that the CEDIA
      MPA immunoassay, run on the Hitachi 911 analyzer, over-estimates plasma MPA
      concentrations with a magnitude that is influenced by transplant type. Hence,
      users must interpret the immunoassay results with caution and not assume that the
      metabolite fraction is constant in recipients of the same organ type or in
      different organ transplant populations.

PMID- 17038878
TI  - Is C2 monitoring or another limited sampling strategy superior to C0 monitoring
      in improving clinical outcomes in adult liver transplant recipients?
AB  - Cyclosporine (CsA) has had a major impact on the process and success of solid
      organ transplantation. Early in the use of CsA, therapeutic monitoring using the
      predose (trough, or C0) concentration became the standard of care. However, there
      are complications with the use of C0 monitoring that have only partly been
      mitigated with the advent of the micro-emulsion formulation (CsA-ME). More
      recently, limited sampling strategies (LSSs) for measuring the area under the CsA
      concentration-time curve (AUC) have been investigated to improve the monitoring
      of CsA post-transplantation. Many centres now routinely monitor CsA therapy using
      the concentration at 2 hours postdose (C2). In this paper the strength of the
      evidence for C2 (or other LSSs) relative to C0 monitoring of CsA-ME for improving
      clinically important outcomes in liver transplant patients is critically
      examined. Additionally, gaps in the literature are identified and recommendations
      are made for clinical research that could be done to provide more definitive
      evidence for the use of C2 or other LSSs in monitoring liver transplant patients.

PMID- 17038879
TI  - Mycophenolic acid formulation affects cyclosporine pharmacokinetics in stable
      kidney transplant recipients.
AB  - A novel monitoring strategy based on the blood concentration at two hours post
      dose (C2) has been recently proposed for the assessment of cyclosporine (CsA)
      absorption and daily exposure, and therapeutic windows for C2 levels have been
      identified. These guidelines have been derived from patients given mycophenolate
      mofetil (MMF) or azathioprine, and never tested in those treated with the enteric
      coated formulation of mycophenolic acid (EC-MPS). The authors have compared full
      CsA pharmacokinetic evaluations in 12 kidney transplant recipients given EC-MPS
      with those from 20 patients on MMF at months 6, 12, 18 and 24 postsurgery. At
      month 6 postsurgery, patients on EC-MPS had a shift to the right in the CsA peak
      concentration as compared to that in patients given MMF, an effect associated
      with significant differences in CsA Tmax (1.9 +/- 0.3 h vs. 1.5 +/- 0.6 h, P <
      0.05), C2 (988 +/- 259 vs. 720 +/- 214 ng/mL, P < 0.01), and C3 levels (539 +/-
      119 vs. 435 +/- 119 ng/mL, P < 0.05). Interestingly, the authors found that the
      majority of patients on EC-MPS had CsA peaking at 2-h postdosing, whereas most of
      patients on MMF had CsA Cmax at 1 h. Similar results were observed also at months
      12, 18, and 24 postsurgery. These findings indicate that the pharmacokinetics of
      CsA is significantly affected by the concomitant administration of different MPA
      formulations. This would imply the need of specific algorithms to adequately
      estimate CsA dose adjustment in patients given, in addition to CsA, EC-MPS or
      MMF.

PMID- 17038880
TI  - A retrospective TDM database analysis of interpatient variability in the
      pharmacokinetics of lopinavir in HIV-infected adults.
AB  - Lopinavir is one of the most-widely used protease inhibitors in the treatment of
      HIV-1 infected patients. Concentration-effect relationships have been described
      for both antiviral activity and toxicity. Less is known about patient
      characteristics that may determine interpatient variability in lopinavir plasma
      concentrations. A database was created containing all Therapeutic Drug Monitoring
      (TDM) results collected at our Department. Patients were included if they were
      using lopinavir twice daily for at least two weeks; subjects who were known to be
      nonadherent (based on either a lopinavir concentration <0.2 mg/L or suspected by
      the physician) were excluded. Demographic data were collected from TDM
      application forms and patient charts. Patients attending one of the 22 HIV
      treatment centers in The Netherlands. The Department of Clinical Pharmacy is a
      national referral center for TDM of antiretroviral agents. Lopinavir
      concentration ratios (CRs) were calculated for each patient by dividing the
      individual plasma concentration by the time-adjusted population value.
      Relationships with lopinavir CRs were tested using regression analysis and
      analysis of variance. A total of 802 patients were included (607 males; 150
      females; 45 unknown). The age and body weight of the patients ranged from 18 to
      74 years (mean 42) and 42 to 121 kg (mean 72), respectively. Race was known for
      756 persons: Caucasian 76%, African 18% and Asian 6%. The median (+ interquartile
      range, IQR) lopinavir CR was 0.98 (IQR: 0.67-1.31). Body weight showed an inverse
      relationship with lopinavir CR (F = 23.1; P < 0.001). Age was not related with
      lopinavir CR (P = 0.99). Female patients had a significantly higher lopinavir CR
      than males: 1.18 vs. 1.03 (P = 0.005); race was not associated with differences
      in lopinavir CR. In a multivariate regression analysis body weight, but not
      gender, remained significantly related to lopinavir CR. Body weight is the only
      demographic factor that could be related to lopinavir exposure; clinicians should
      be alert for an increased risk of suboptimal antiviral efficacy in patients with
      high body weight, and for an increased risk of toxicity in patients with a low
      body weight.

PMID- 17038881
TI  - Pharmacokinetics of intravenous rifampicin (rifampin) in neonates.
AB  - Few reports have addressed neonatal rifampicin plasma concentrations and data on
      neonatal rifampicin pharmacokinetics are completely lacking. Therefore, plasma
      concentrations of rifampicin and its main metabolite 25-O-desacetylrifampicin
      (DES) were measured in 123 surplus plasma samples from routine vancomycin
      monitoring in 21 neonates using reversed-phase HPLC. Rifampicin peak and trough
      plasma concentrations were 4.66 +/- 1.47 mg/L and 0.21 +/- 0.20 mg/L,
      respectively, after a dose of 8.5 +/- 2.1 (mean +/- SD) mg/kg per day. A
      significant linear relationship between rifampicin dose and peak plasma
      concentrations was found, but inter-patient variability was high. Pharmacokinetic
      parameters of rifampicin were calculated according to a one-compartment open
      model with iterative two-stage Bayesian fitting (MW?PHARM 3.60, Mediware, The
      Netherlands). First-order elimination constant, volume of distribution corrected
      for weight, total body clearance corrected for weight (CL/W), and elimination
      half-life were 0.16 +/- 0.06 h(-1), 1.84 +/- 0.59 L/kg, 0.28 +/- 0.11 Lkg(-1) h(
      1), and 4.9 +/- 1.7 h, respectively. A high Pearson correlation was found between
      CL/W rifampicin and the covariates plasma creatinine and CL/W gentamicin of a
      preceding gentamicin treatment course, r = 0.728 (n = 17) and r = 0.837 (n = 12),
      respectively. DES was detected in each plasma sample. Therefore, rifampicin seems
      to be eliminated by both renal and metabolic pathways in neonates. In 8 study
      patients, plasma concentrations of rifampicin and DES were measured again after
      two weeks of therapy. CL/W rifampicin was significantly higher (67 +/- 50%). The
      authors suggest maintaining the current dose regimen of 10 mg/kg once a day.
      Because of the large inter-patient variability in rifampicin plasma
      concentrations and CL/W increase during therapy, the authors suggest monitoring
      rifampicin peak and trough plasma concentrations to avoid low plasma
      concentrations. More research is needed to determine well-founded dosing
      guidelines.

PMID- 17038882
TI  - False-positive serum tricyclic antidepressant concentrations using fluorescence
      polarization immunoassay due to the presence of hydroxyzine and cetirizine.
AB  - A recent report indicates that hydroxyzine and its active metabolite cetirizine
      interfere with the PENTINA carbamazepine assay. The potential interference of
      hydroxyzine and cetirizine with the fluorescence polarization immunoassay (FPIA)
      and CEDIA assay of carbamazepine as well as with the fluorescence polarization
      immunoassay of tricyclic antidepressants (TCA) was studied. Aliquots of drug-free
      serum pools were supplemented with various concentrations of hydroxyzine and
      cetirizine representing therapeutic, mild to moderate toxic as well as very toxic
      concentrations. Then apparent carbamazepine and TCA concentrations were measured
      by immunoassays. Although no interference of hydroxyzine and cetirizine was
      observed with carbamazepine assays (FPIA and CEDIA), significant apparent TCA
      concentrations were observed when aliquots of drug-free serum were supplemented
      with hydroxyzine or cetirizine. Mathematical formula was devised to predict
      hydroxyzine and/or cetirizine concentration in serum based on observed apparent
      TCA levels. Hydroxyzine and cetirizine also falsely increased total TCA values
      when aliquots of serum pool prepared from patients receiving TCA were further
      supplemented with these drugs. In conclusion, hydroxyzine and cetirizine do not
      interfere with the FPIA and CEDIA carbamazepine assays but interfere with the
      measurement of total TCA using the FPIA.

PMID- 17038883
TI  - The relationship between P-glycoprotein (PGP) polymorphisms and response to
      olanzapine treatment in schizophrenia.
AB  - P-glycoprotein (PGP) is a polymorphic efflux transporter located on the blood
      brain barrier that potentially affects the penetration of atypical antipsychotics
      into the central nervous system. Increased antipsychotic penetration to the
      primary site of activity may result in greater symptom improvement or the
      occurrence of side effects. This investigation examined the relationship between
      three common PGP polymorphisms (C1236T, G2677TA, and C3435T) and response to 6
      weeks of open-label olanzapine treatment in patients with schizophrenia.
      Individuals with a PGP T allele at any of these polymorphisms would be expected
      to have greater antipsychotic penetration through the blood brain barrier, due to
      lower PGP activity. Forty-one patients were included in this reanalysis. For
      subjects in the 3435T allele carrier group, the plasma olanzapine level alone was
      positively associated with percent change in Brief Psychiatric Rating Scale score
      (p = 0.02). This relationship was not seen for the 3435CC group (p = 0.583). A
      similar trend was observed for negative symptom reduction, olanzapine plasma
      concentration, and the 3435T allele (p = 0.06), but this relationship did not
      meet statistical significance. There was no relationship between the PGP
      genotypes and changes in weight over the course of this 6 week study. The
      analysis using C1236T or G2677AT genotypes gave similar results, due to linkage
      of these polymorphisms.PGP polymorphisms may affect the penetration of olanzapine
      into the central nervous system as seen by a relationship between the 3435T
      allele, olanzapine plasma levels, and reduction in the positive symptoms of
      schizophrenia. This may stem from greater olanzapine central nervous system
      latency due to the presence of the 3435T allele and reduced PGP activity. The PGP
      C3435T genotype may help to determine positive symptom reduction from olanzapine
      clinically, but these findings should be replicated in a larger sample of
      subjects.

PMID- 17038884
TI  - AmpliChip CYP450 GeneChip: a new gene chip that allows rapid and accurate CYP2D6
      genotyping.
AB  - Methods for Cytochrome P450-2D6 (CYP2D6) genotyping are often time-consuming and
      laborious, which can restrict their use in pretherapeutic screening programs.
      Gene chip technology could overcome this problem. The aim of this study was to
      evaluate CYP2D6 genotyping by a new improved gene chip compared to a PCR-RFLP
      method. AmpliChip CYP450 GeneChip(R) (AmpliChip) is a microarray hybridization
      method for genotyping CYP2D6 and CYP2C19. One hundred fifty-nine DNA samples were
      genotyped both by AmpliChip as well as by PCR-RFLP and, where applicable, by a
      SNaPshot technique which detects single nucleotide polymorphisms based on the
      single base extension principle. In 152 of the 159 samples, CYP2D6 genotypes
      determined with the AmpliChip were in accordance with the results of PCR-RFLP.
      All seven discrepant samples had gene duplications and were subjected to SNaPshot
      analysis. SNaPshot results concurred with those of the AmpliChip for six out of
      seven samples. In the one divergent result, DNA sequencing confirmed that the
      AmpliChip had assigned the correct genotype. In conclusion, AmpliChip is a highly
      reliable method for CYP2D6 genotyping that allows the correct determination of
      all relevant CYP2D6 alleles in one single run. It therefore represents a very
      efficient and fast method, offering new perspectives for the application of
      pharmacogenetics in clinical medicine.

PMID- 17038885
TI  - A rapid and inexpensive method for anticipating severe toxicity to fluorouracil
      and fluorouracil-based chemotherapy.
AB  - Dihydropyrimidine dehydrogenase (DPD) deficiency leads to dramatic overexposure
      to fluorouracil (5-FU), resulting in a potentially lethal outcome in patients
      treated with standard doses. The aim of this study was to validate, in a routine
      clinical setting, a simple and rapid method to determine the DPD status in a
      subset of cancer patients, all presenting with life-threatening toxicities
      following 5-FU or capecitabine intake. In this study, 80 out of 615 patients
      (13%) suffered severe toxicities, including 5 lethal ones (0.8%), during or after
      chemotherapy with a fluoropyrimidine drug. Patients with severe toxicities were
      treated with 5-FU (76 patients) or capecitabine-containing protocols (4
      patients). Simplified uracil to di-hydrouracil (U/UH2) ratio determination in
      plasma was retrospectively performed in these 80 patients, as a surrogate marker
      of DPD activity. When possible, 5-FU Css determination was performed, and
      screenings for the canonical IVS14+1G>A mutation were systematically carried out.
      Comparison of the U/UH2 ratios with a reference, non-toxic population, showed
      abnormal values suggesting impaired DPD activity in 57 out of the 80 toxic
      patients (71%) included in this study, and in 4 out of 5 patients (80%) with a
      fatal outcome. Similarly, drug exposures up to 15 times higher than the range
      observed in the non-toxic population were also observed. Importantly, no
      IVS14+1G>A mutation was found in these patients, including those displaying the
      most severe or lethal toxicities. These data warrant systematic detection of DPD
      deficient patients prior to fluoropyrimidine administration, including when oral
      capecitabine (Xeloda) is scheduled. Finally, the simplified methodology presented
      here proved to be a low cost and rapid way to identify routinely patients at risk
      of toxicity with 5-FU or capecitabine.

PMID- 17038886
TI  - Pitfalls in TDM of antibiotic drugs: analytical and modelling issues.
AB  - The quality assurance program of the Dutch KKGT [Association for Quality
      Assessment in therapeutic drug monitoring (TDM) and Clinical Toxicology] has been
      running for more than 25 years. One of these programs concerns TDM of the
      antibiotic drugs gentamicin, tobramycin, amikacin, and vancomycin. We present two
      issues encountered in a recent survey. In a case of gentamicin monitoring and
      dose-adjustment, a systematic analytical error in some centers led to a dosing
      recommendation that differed from that of the organizers. Correction of the
      analytical results on the basis of a standard control sample resulted in
      concentration differences of more than 20% and different dosing recommendations
      in these centers. In a case of vancomycin TDM, the choice of the population model
      proved to be critical for dose adjustment. We illustrate this example by
      presenting the plasma profiles derived from the different population models used
      by the participants.

PMID- 17038887
TI  - Identification of a sibutramine-metabolite in patient urine after intake of a
      "pure herbal" Chinese slimming product.

PMID- 17038888
TI  - Pharmacokinetic characterization of amantadine in human brain tissue.
AB  - Amantadine concentrations in human brain tissue were assessed in order to
      estimate population pharmacokinetic parameters using the computer program NONMEM.
      The elimination constant in brain tissue was determined to be 0.00447 [1/h],
      resulting in a t1/2 of 6.5 days for the mean patient in the population
      investigated (n = 19). An estimate of 65.5 L was obtained for the apparent volume
      of distribution. The elimination half-life of amantadine from brain tissue is
      much longer than from blood and is comparable to the previously investigated
      neuroleptic drugs haloperidol and levomepromazine.

PMID- 17038889
TI  - Therapeutic monitoring of clozapine in Australia: the need for consensus.
AB  - In the absence of well-defined guidelines for the monitoring of plasma
      concentrations of clozapine, this study examined the practices of seven
      laboratories from four states in Australia. Laboratories analyzed 5 freeze-dried
      serum samples containing a mixture of clozapine and norclozapine in varying
      concentrations and the measurement data were analyzed for accuracy and precision.
      Additional information on laboratory practices was obtained through questionnaire
      responses. Measurement precision amongst the laboratories was good but there were
      significant differences in the accuracy of measurements from one laboratory.
      There were differences in the ranges for which assays had been validated and in
      suggested therapeutic ranges. These differences could have a significant impact
      on the interpretation of measured concentrations and patient care, and emphasize
      the need for consensus in this area. Repeat concentration measurements are
      recommended in the case of drug concentration measurements that are inconsistent
      with clinical observations or previous measurements.

PMID- 17038890
TI  - Quantification of Delta9-tetrahydrocannabinol and its major metabolites in
      meconium by gas chromatographic-mass spectrometric assay: assay validation and
      preliminary results of the "meconium project".
AB  - A rapid and simple procedure based on gas chromatography-mass spectrometry (GC
      MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11
      hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol
      9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta
      THC) and deuterated THC-COOH as internal standards. The biological matrix was
      subjected to liquid-liquid extraction after enzyme hydrolysis for conjugated
      analytes.Chromatography was performed on a fused silica capillary column and
      analytes were determined in the selected-ion-monitoring (SIM) mode. The method
      was validated in the range 20 to 500 microg/g using 1g of meconium per assay. The
      method was applied to the analysis of meconium in a cohort of newborns to assess
      eventual fetal exposure to cannabis. Within positive samples, THC-COOH and THC-OH
      (range: 33.7 to 182.1 and 20.7 to 493.3 microg/g, respectively) were both present
      in the majority of cases with only 1 specimen with THC-OH as the most abundant
      metabolite and 2 with THC only.

PMID- 17038891
TI  - No influence of 3435C>T ABCB1 (MDR1) gene polymorphism on risk of adult acute
      myeloid leukemia and P-glycoprotein expression in blast cells.
AB  - Inherited differences in xenobiotic transport and metabolism may play an
      important role in the development of adult acute myeloid leukemia (AML) and
      response to the chemotherapy. An ATP-binding cassette (ABC) family transporter P
      glycoprotein (P-gp or ABCB1), encoded by ABCB1 (MDR1) gene, is involved in the
      protection against xenobiotics and multi-drug resistance. The aim of this study
      was to investigate the potential involvement of the ABCB1 gene exon 26 3435C>T
      single nucleotide polymorphism (SNP) in the genetic susceptibility to AML and
      regulation of P-gp expression and activity in AML cells. A total of 180 adult AML
      patients and 180 sex-matched controls were genotyped using PCR-RFLP method.
      Moreover, in 40 AML patients ABCB1 gene expression was studied by real-time RT
      PCR and P-gp expression and activity were assessed by flow cytometry assays. The
      prevalence of 3435C>T ABCB1 polymorphism was similar in patient and control
      cohorts (P = 0.16). Furthermore, the carriers of different ABCB1 genotypes did
      not differ significantly according to ABCB1 gene expression (P = 0.99), P-gp
      expression (P = 0.42) and P-gp activity (P = 0.83) in leukemic cells. The authors
      conclude that isolated 3435C>T ABCB1 SNP is not a major factor of the genetic
      susceptibility to adult AML, and that genotyping of this polymorphism does not
      allow predicting P-gp expression or activity in AML cells.

PMID- 17038892
TI  - Contextualizing methadone-related deaths: failure to contextualize may be
      considered a weapon against public health.

PMID- 17038894
TI  - Measuring unbound versus total valproate concentrations for therapeutic drug
      monitoring.

PMID- 17038895
TI  - Clinical relevance of TDM of SSRIs.

PMID- 17038897
TI  - Treatment of hepatitis C virus infection (HCV) after renal transplantation:
      implications for HCV-positive dialysis patients awaiting a kidney transplant.
AB  - Patient survival is significantly lower in hepatitis C virus (HCV)-positive
      compared to HCV-negative dialysis patients. After renal transplantation,
      immunosuppressive therapy can result in an increased burden of HCV viremia. Both
      patient and graft survivals are lower in HCV-positive compared to matched HCV
      negative renal-transplant patients. Therefore, it is important to treat HCV
      infection. At present, after renal transplantation, there is no current safe and
      efficient therapy. Alpha-interferon (alpha-IFN) does not give a sustained
      virological response, and is associated with a high rate of renal failure.
      Ribavirin and amantadine monotherapies are associated with a significant
      improvement in liver enzymes, but have no impact upon HCV viremia. Ribavirin,
      however, may be indicated in cases of HCV-related glomerulopathy because it can
      significantly decrease proteinuria. The combined use of alpha-IFN and ribavirin
      should only be given to those patients who have developed posttransplant
      fibrosing cholestatic hepatitis. Therefore, HCV infection needs to be treated
      pretransplant. In dialysis patients, the only recommended therapy, as yet, is
      alpha-IFN monotherapy. Pegylated alpha-IFN is under evaluation and ribavirin is
      contraindicated because it results in severe hemolytic anemia. Twelve months of
      alpha-IFN therapy results in sustained virological clearance in approximately 40%
      of patients, regardless of their genotype. HCV RNA, after three months of alpha
      IFN therapy, is a predictive factor for a long-term sustained response. Finally,
      when HCV-positive dialysis patients with a sustained virological response undergo
      successful renal transplantation, very few suffer a virological relapse, thus
      emphasizing that these patients were cured.

PMID- 17038898
TI  - Antibody and complement mediated injury in transplants following sensitization by
      allogeneic blood transfusion.
AB  - BACKGROUND: Many patients on the waiting list for transplants are sensitized from
      previous blood transfusions, pregnancy, or transplants. We investigated the role
      of complement in acute and chronic pathology in hearts transplanted to sensitized
      rats. METHODS: Blood was transfused from allogeneic PVG.R8 rats or control
      isogeneic PVG.1U rats to C6-sufficient and -deficient PVG.1U rats. Three weeks
      later hearts were transplanted from PVG.R8 donors and low-dose cyclosporin A was
      initiated. RESULTS: Allogeneic but not isogeneic blood transfusion elicited
      strong immunoglobulin (Ig) M, IgG1 and IgG2b alloantibody responses.
      Sensitization caused accelerated acute rejection of cardiac allografts by C6
      sufficient recipients (4 days). In contrast, allografts functioned over 40 days
      in all C6-deficient recipients, but sensitization caused increased interstitial
      fibrosis and chronic vasculopathy. Circulating alloantibodies were associated
      with deposits of C4d on the vascular endothelium together with pericapillary
      accumulation of neutrophils and macrophages in the grafts. In contrast, T cells
      accumulated in periarterial lymphatics that did not have C4d deposits.
      CONCLUSIONS: Presensitization by allogeneic blood transfusion causes accelerated
      acute graft rejection in the presence of the complete complement cascade. In the
      absence of C6, macrophages colocalized with deposits of C4d and T cells
      accumulated in the periarterial lymphatics.

PMID- 17038899
TI  - Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic
      rats.
AB  - BACKGROUND: Experimental therapeutics for degenerative and traumatic diseases of
      the nervous system have been recently enriched with the addition of neural stem
      cells (NSCs) as alternatives to fetal tissues for cell replacement.
      Neurodegenerative diseases present the additional problem that cell death signals
      may interfere with the viability of grafted cells. The adult spinal cord raises
      further challenges for NSC differentiation because of lack of intrinsic
      developmental potential and the negative outcomes of several prior attempts.
      METHOD: NSCs from human fetal spinal cord were grafted into the lumbar cord of
      SOD1 G93A rats. The differentiation fate of grafted NSCs and their effects on
      motor neuron number, locomotor performance, disease onset, and survival
      trends/longevity were assessed. Trophic mechanisms of observed clinical effects
      were explored with molecular and cellular methodologies. RESULT: Human NSCs
      showed extensive differentiation into neurons that formed synaptic contacts with
      host nerve cells and expressed and released glial cell line-derived neurotrophic
      factor and brain-derived neurotrophic factor. NSC grafts delayed the onset and
      progression of the fulminant motor neuron disease typical of the rat SOD1 G93A
      model and extended the lifespan of these animals by more than 10 days, despite
      the restricted grafting schedule that was limited to the lumbar protuberance.
      CONCLUSION: NSC grafts can survive well in a neurodegenerative environment and
      exert powerful clinical effects; at least a portion of these effects may be
      related to the ability of these grafts to express and release motor neuron growth
      factors delivered to host motor neurons via graft-host connections.

PMID- 17038900
TI  - Racial disparities in living kidney donation: is there a lack of willing donors
      or an excess of medically unsuitable candidates?
AB  - BACKGROUND: Live kidney donation is safe for healthy donors and an effective
      treatment for patients with end-stage renal disease. Many potential donors are
      referred for live kidney donation, but only a small percentage donate. This study
      aims to determine reasons for nondonation and establish if racial differences
      exist. METHODS: A retrospective database and chart review of all patients that
      were referred for potential live kidney donation from January 1, 2000 to December
      31, 2004 was conducted. RESULTS: In all, 30.3% of referred potential live kidney
      donors were lost to follow-up. Primary reasons for nondonation (n=1,050) included
      unsuitable donor health (43.1%) and recipient-based causes (41.3%). Immunologic
      incompatibility accounted for 9.7% of all nondonations. Racial differences
      indicated more African Americans had incompatible blood types (P=0.01) or
      ineligible recipients (26.7% vs. 14.4%, P<0.01). More non-African Americans
      donated (13.2% vs. 4.6%, P<0.01) or were halted because the potential recipient
      received another organ (living/cadaveric) (20.0% versus 7.9%, P<0.01).
      Nondonation due to overall donor health (including diabetes and hypertension) did
      not differ between races, but subanalysis indicated more African American
      nondonation was due to high body mass index (P=0.01). CONCLUSIONS: Determining
      the reason behind nondonation is a first step towards understanding low rates of
      live kidney donation. More African American donor referrals are lost to follow-up
      while rates of other reasons were similar among races. This may indicate that
      African Americans are not more frequently medically unsuitable, but that the
      divergence in rates of live kidney donation is caused by a disparity in
      willingness to donate among African Americans.

PMID- 17038901
TI  - Kidney transplant outcomes in the indigenous population in the Northern Territory
      of Australia.
AB  - BACKGROUND: Indigenous Australians develop end-stage renal disease (ESRD) at a
      significantly higher rate than nonindigenous Australians. Renal transplantation
      is the preferred treatment modality; however, they are underrepresented in the
      transplanted population. In addition, despite the morbidity and mortality gains
      demonstrated in other patient groups, it is unclear whether such an advantage is
      replicated for indigenous Australians. We have sought to identify some of the
      factors that lead to poorer outcomes within this group of recipients. METHODS: We
      performed a retrospective analysis of a cohort of renal transplant recipients
      (indigenous and nonindigenous) from the Northern Territory of Australia. RESULTS:
      Indigenous patients waited longer on dialysis, were more sensitized at the time
      of transplantation, and the number of human leukocyte antigen mismatches was
      greater. Overall renal allograft survival is poorer among indigenous Australians
      (HR 4.13, 2.0-8.5, P<0.0001) with the majority of grafts lost due to recipient
      death. The most common cause of death was septicemia. Graft loss due to any cause
      has not been influenced by the absence of full-time specialist staff at major
      treatment centers. Infection rates are greatly increased in indigenous patients
      (RR 4.1, 95% CI 3.5-4.7, P<0.0001), in addition to the incidence of rejection (RR
      2.5 95% CI 1.8-3.5, P<0.001) and hospitalization (RR 3.9, 95% CI 3.2-4.9,
      P<0.0001). There is increased steroid exposure among indigenous recipients.
      CONCLUSIONS: Indigenous recipients of cadaveric kidney transplants have worse
      outcomes than nonindigenous recipients, mostly due to increased mortality and
      morbidity from infective causes.

PMID- 17038902
TI  - Portopulmonary hypertension in the early phase following liver transplantation.
AB  - BACKGROUND: Portopulmonary hypertension (PPH) is a severe complication of liver
      cirrhosis, which poses a high risk for postliver transplantation (LT) mortality.
      In most liver transplant centers, severe PPH is viewed as an absolute
      contraindication for LT, but recent reports challenge this. The purpose of our
      study was to determine the incidence of PPH, its influence on the 30-day
      mortality rate following LT and to determine the sensitivity and specificity of
      Doppler echocardiography and electrocardiography as noninvasive tools to
      determine PPH. METHODS: We studied 74 consecutive patients that underwent LT
      between February 2004 and November 2005. Pulmonary arterial pressure and cardiac
      index were repeatedly determined during surgery and postoperatively. PPH was
      defined as mild (mean pulmonary arterial pressure (MPAP) 25-35 mm Hg), moderate
      (MPAP of 35-45 mm Hg) and as severe (MPAP >45 mm Hg). RESULTS: The total
      incidence of PPH was 31% (16 mild, 5 moderate, and 2 severe). There was a
      tendency towards increased 30-day mortality rate in patients with PPH compared to
      controls (22% vs. 12%, P=0.1). However, the two patients with the most severe PPH
      survived. The duration of ventilation and total stay at the intensive care unit
      did not differ significantly between groups. The positive predictive value of
      Doppler echocardiography for PPH was 39% and the negative predictive value 90%.
      CONCLUSIONS: Mild pulmonary hypertension is common in patients with liver
      failure, whereas moderate and severe hypertension is not. Severe PPH should not
      be considered as absolute contraindication for LT.

PMID- 17038903
TI  - The current practice of live donor nephrectomy in Europe.
AB  - BACKGROUND: The increasing number of live kidney donors in the last decade has
      stimulated interest in the surgical technique of donor nephrectomy. In this
      study, we evaluated the current status of the surgical approach in European
      transplant centers. METHODS: A questionnaire was sent to 131 centers in 12
      European countries. Questions included the number of donors, the technique used,
      and the inclusion and exclusion criteria for a technique. RESULTS: Ninety-two
      replies (70%) were included. In the responding centers, approximately 1450 live
      donor nephrectomies were performed in 2004 (more than 80% of all live kidney
      donations in these countries). The number of living donors ranged from 0 to 95
      per center. Nineteen institutions (21%) removed kidneys using endoscopic
      techniques only. Twenty-two centers (24%) performed both open and laparoscopic
      donor nephrectomy. Vessel length, difficult anatomy and right-sided donor
      nephrectomy were common reasons to choose an open technique. Twelve centers had
      performed laparoscopic donor nephrectomy but quit their program for various
      reasons. In 51 centers (55%), only open donor nephrectomy was carried out. Lack
      of evidence that endoscopic techniques provide better results was the main reason
      for these centers to stick to an open approach. Incisional hernias occurred after
      all types of open surgery in up to 30% of the donors per center. Twenty-nine
      clinics still carry out the classic flank incision. CONCLUSION: The surgical
      technique of live donor nephrectomy varies greatly between transplant centers in
      European countries. To define the optimal surgical approach a European
      registration of donor nephrectomies would be helpful.

PMID- 17038904
TI  - Developing a prognostic model for 90-day mortality after liver transplantation
      based on pretransplant recipient factors.
AB  - BACKGROUND: Current statistical prognostic models for mortality after liver
      transplantation do not have good discriminatory ability. Furthermore, the
      methodology used to develop these models is often flawed. The objective of this
      paper is to develop a prognostic model for 90-day mortality after liver
      transplantation based on pretransplant recipient factors, employing a rigorous
      model development method. METHODS: We used data on 4,829 patient that were
      prospectively collected for the UK & Ireland Liver Transplant Audit. Switching
      regression was employed to impute missing values combined with a bootstrapping
      approach for variable selection. RESULTS: In all, 452 patients (9.4%) died within
      90 days of their transplantation. The final prognostic model was well calibrated
      and discriminated moderately well between patients who did and who did not die (c
      statistic 0.65, 95% CI [0.63, 0.68]). Although discrimination was not excellent
      overall, the results showed that those patients with a "low" chance of dying
      within 90 days of their transplant and those with a "high" chance of dying could
      be differentiated from patients with a "intermediate" chance. CONCLUSIONS: Our
      model can provide transplant candidates with predictions of their early
      posttransplantation prospects before any donor information is known, which is
      essential information for patients with end-stage liver disease for whom liver
      transplantation is a treatment option.

PMID- 17038905
TI  - Sirolimus interferes with iron homeostasis in renal transplant recipients.
AB  - BACKGROUND: Sirolimus is an immunosuppressive drug whose use is frequently
      associated with anemia. A pathogenic link between sirolimus-induced anemia and
      the appearance of an inflammatory state was recently suggested. Because
      inflammation-related anemia is characterized by a functional iron deficiency, we
      investigated whether sirolimus may influence iron homeostasis and serum levels of
      hepcidin, a key mediator of inflammation-related anemia. METHODS: To this
      purpose, 42 consecutive transplanted patients with biopsy-proven chronic
      allograft nephropathy were randomized (2:1 ratio) to receive either a 40%
      cyclosporine reduction (group A, 14 patients) or immediate cyclosporine
      withdrawal and sirolimus introduction (group B, 28 patients). Hemoglobin levels
      and iron status were evaluated 6 months before and after randomization. RESULTS:
      The two groups had similar hemoglobin levels and iron status at baseline. We did
      not observe any significant change in hemoglobin and iron status in group A
      patients after randomization. On the contrary, we observed a significant
      reduction of hemoglobin without any change of red blood cell count after
      sirolimus introduction, with a significant reduction of mean corpuscular volume
      and mean corpuscular hemoglobin. Serum iron and transferrin saturation (TSAT)
      levels were markedly reduced after the switch, while ferritin serum
      concentrations remained stable. Although sirolimus-induced anemia was recently
      suggested to resemble inflammation-related anemia, hepcidin serum levels were
      similar in the two groups after randomization. None of group A and eight of group
      B patients presented a TSAT <20 and were given iron supplementation after
      randomization, in all of them oral iron therapy did not influence either
      hemoglobin or serum iron levels. CONCLUSION: We demonstrated that sirolimus
      induced anemia is independent of the drug antiproliferative effect and does not
      present the features of inflammation-related anemia. This event may be due to the
      direct influence of sirolimus on iron homeostasis.

PMID- 17038906
TI  - Unrelated versus related allogeneic stem cell transplantation after reduced
      intensity conditioning.
AB  - BACKGROUND: The use of reduced intensity conditioning (RIC) regimens in
      allogeneic hematopoietic stem cell transplantation (HSCT) has increased over the
      past five years. PATIENTS: In this study, involving 137 patients, we compared the
      outcome after RIC in patients receiving grafts from matched unrelated donors
      (MUD; n=74) and sibling donors (n=63). The MUD and sibling groups were comparable
      regarding diagnosis, including solid tumors and hematological malignancies, and
      conditioning regimens. RESULTS: Engraftment was successful in most patients
      (88%), with no significant difference between MUD and sibling transplants.
      Cytomegalovirus (CMV) infection was more common in the MUD group (65%) than in
      the sibling group (46%) (P=0.04). No difference in severe acute graft-versus-host
      disease (GVHD) was found between the groups. However, the incidence of chronic
      GVHD was higher after sibling transplants. This was probably due to higher donor
      age in this group, since this was the only significant risk factor for chronic
      GVHD in multivariate analysis. The incidence of transplant related mortality
      (TRM) was significantly higher after MUD transplantation (40%) than after sibling
      transplantation (16%) (P<0.01). Because relapse/disease progression was more
      common after sibling transplantation, there was no significant difference in
      overall survival between the two groups. CONCLUSION: Using unrelated donors after
      RIC is feasible, but it resulted in more CMV infection and increased transplant
      related mortality. Survival was comparable to that of sibling transplants.

PMID- 17038907
TI  - Impaired arterial compliance and aerobic endurance in kidney transplant
      recipients.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of morbidity and
      mortality in kidney transplant recipients (KTR). Two risk factors for
      cardiovascular disease that have not been examined in this population are
      arterial compliance and aerobic capacity. The primary objective was to determine
      small and large artery compliance and aerobic endurance in KTR. A secondary
      objective was to explore the relationship between aging and arterial compliance
      and aerobic endurance in KTR. METHODS: Sixty-two clinically stable KTR were
      recruited from the University of Alberta Renal Transplant Clinic. Small and large
      artery compliance was assessed using computerized arterial pulse waveform
      analysis. Aerobic endurance was determined using the six-minute walk test. Age
      matched normative data from healthy individuals was used for comparison. RESULTS:
      Small arterial compliance was lower in KTR (5.5+/-3 ml/mm Hg x 100) compared to
      age-matched healthy individuals' predicted values (7.9+/-0.9 ml/mm Hg x 100,
      P<0.0001). No difference was found for large artery compliance between KTR
      (16.0+/-6.6 ml/mm Hg x 10) and age-matched healthy predicted values (15.2+/-1.3
      ml/mm Hg x 10, P=0.5). Small and large artery compliance were 35% (P=0.026) and
      36% (P=0.005) higher in younger (<51 years) versus older (>51 years) KTR,
      respectively. The six-minute walk distance was 28% lower in KTR (495+/-92 m)
      compared to healthy age-predicted values (692+/-56 m P<0.0001). CONCLUSIONS:
      Compromised arterial compliance and poor aerobic endurance may partially explain
      the high incidence of cardiovascular disease in KTR. Interventions demonstrated
      to improve these parameters may afford substantial clinical benefit in this
      population.

PMID- 17038908
TI  - A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal
      function and cardiovascular risk factors in kidney transplant recipients.
AB  - BACKGROUND: There are few data directly comparing the effects of two-hour
      postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0
      Tac) on renal function and cardiovascular risk factors. METHODS: We studied 378
      (202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto,
      Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in
      estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of
      diet in renal disease four-variable equation), mean arterial pressure (MAP),
      total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months
      posttransplant. The independent effect of treatment/monitoring strategies on
      continuous outcomes and time-to-NODM was modeled using linear and Cox regression,
      respectively. RESULTS: Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6
      vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple
      linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2
      CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64
      ml/min between months one and six posttransplant. There was no significant
      difference in average MAP and TC. In a stepwise multivariable Cox model and a
      propensity score analysis, there was no significant association between the type
      of treatment/monitoring strategy and time-to-NODM. CONCLUSIONS: There was a
      greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six
      months posttransplant. However, MAP, TC, and the risk of NODM were comparable in
      both treatment/monitoring groups. The long-term impact of short-term reductions
      in eGFR as a function of the type of treatment/monitoring strategy requires
      further study.

PMID- 17038909
TI  - Curcumin has potent liver preservation properties in an isolated perfusion model.
AB  - BACKGROUND: Curcumin has profound antioxidant and anti-inflammatory properties.
      This research assessed the effect of curcumin on liver preservation. METHODS:
      Sprague-Dawley rat livers were flushed with different preservation solutions
      [Euro-Collins solution (EC), phosphate buffer saline (PBS), University of
      Wisconsin solution (UW)] with or without curcumin (25-200 microM) and stored at 4
      degrees C for 24-48 hours. Livers were then perfused for 120 minutes via the
      portal vein with oxygenated Krebs-Henseleit bicarbonate buffer solution at a
      pressure of 18 cm H2O in a perfusion apparatus. The livers in the normal (NL)
      group were flushed with EC, PBS, or UW, then immediately perfused (zero
      preservation time). RESULTS: We found that curcumin at 100 microM concentration
      had the optimal preservation characteristics. Portal flow rates and bile
      production were significantly higher and liver enzymes (alanine aminotransferase,
      aspartate aminotransferase, and lactate dehydrogenase) were significantly lower
      in the EC+C livers and PBS+C livers than in the EC or PBS with optimum
      concentration of 100 microM of curcumin. Comparing UW+C vs. UW livers, at 24
      hours there was no difference in these parameters; however, at 36 hours and 48
      hours, portal flow rates and bile production were significantly higher in UW+C
      livers. CONCLUSIONS: We found that curcumin has inherent organ preservation
      quality as it enhanced liver preservation in PBS. In addition, curcumin enhanced
      the preservation quality of EC and UW solutions, thereby extending the
      preservation time while maintaining the organ quality.

PMID- 17038911
TI  - Neonatal porcine islets exhibit natural resistance to hypoxia-induced apoptosis.
AB  - BACKGROUND: Despite the success of the Edmonton protocol for human islet
      transplantation, an alternate source of islet tissue must be developed if beta
      cell replacement therapy is to see widespread application. Neonatal porcine
      islets (NPI) represent one potential source of tissue. When human or rodent
      islets are transplanted, the majority of cells undergo hypoxia-induce apoptosis
      soon after the grafts are placed in the recipient. In the present study, we
      investigated whether NPI were similarly sensitive to hypoxia. METHODS: NPI were
      exposed to hypoxia and hypoxia/reoxygenation using an in vitro hypoxic chamber.
      Afterwards, viability, frequency of apoptosis, and beta-cell function were
      evaluated. NPI and adult porcine islets were transplanted into chemically
      diabetic, immunodeficient mice and graft apoptosis was assessed 24 hours and
      seven days posttransplant. RESULTS: NPI demonstrated a remarkable capacity to
      resist apoptosis and maintain insulin secretion despite severe stresses such as
      hypoxia/reoxygenation. One day after transplantation, NPI grafts showed limited
      apoptosis, confined to rare strongly insulin positive cells. In contrast, adult
      porcine islet grafts underwent widespread apoptosis. Western blotting revealed
      that NPI express high levels of at least one potent endogenous antiapoptotic
      protein (XIAP). CONCLUSIONS: The majority of cells within transplanted human
      islets undergo apoptosis soon after portal infusion. In contrast, NPI have the
      capacity to resist this early posttransplant apoptosis, with likely reduced
      antigen release and diminished immune stimulation. NPI appear to contain a
      population of insulin-low to insulin-negative pre-beta-cells, which are resistant
      to hypoxia-induced apoptosis and still capable of differentiating into mature
      beta-cells.

PMID- 17038910
TI  - Induction of carbon monoxide in donor animals prior to organ procurement reduces
      graft immunogenicity and inhibits chronic allograft dysfunction.
AB  - BACKGROUND: Nonspecific inflammatory damages occurring prior to organ
      transplantation reduce long-term graft survival. Here, we tested the beneficial
      effects of carbon monoxide (CO) induction by methylene chloride (MC). METHODS:
      Fischer-344 (F-344 Rat) or Dark Agouti (DA Rat) donor animals were either treated
      with MC four hours prior to organ removal or remained untreated. Kidneys were
      transplanted into Lewis (LEW) recipients. The low responder strain combination (F
      344-->LEW) was studied for long-term graft changes. Dendritic cells (DCs)
      migration and early changes were followed in additional groups of a high
      responding donor/recipient strain combination (DA-->LEW). Native kidneys of
      uninephrectomized, age-matched normal animals served as controls. RESULTS:
      Following MC application COHb peaked within two hours in donor animals. Renal
      function and morphology improved significantly in renal allografts of CO induced
      donor animals and were comparable to native controls long-term (24 wks). Early
      after transplantation (24 hr) donor-derived DCs, CD4+ T-cells and alloreactive T
      cells were significantly reduced following the engraftment of organs from treated
      donors. In addition, a trend towards a Th1/Th2 shift and a significant intragraft
      reduction of CD3 mRNA expression was observed. CONCLUSION: Donor treatment for
      the induction of CO reduced graft immunogenicity and inhibited chronic allograft
      nephropathy.

PMID- 17038912
TI  - Requirement of CD28 signaling in homeostasis/survival of TGF-beta converted
      CD4+CD25+ Tregs from thymic CD4+CD25- single positive T cells.
AB  - BACKGROUND: The thymus is a major organ that generates "natural" CD4+CD25+ T
      regulatory cells (Tregs). However, the detailed pathway(s) by which Tregs are
      developed remain a mystery. CD28-/- mice have profound decrease in Tregs, but the
      underlying molecular events remain largely undefined. METHODS: CD4+CD25+
      thymocytes from wildtype and CD28-/- mice were cultured with T-cell receptor
      (TCR) and transforming growth factor (TGF)-beta stimulation to generate CD25+
      Tregs and their phenotype and function were studied in vitro and in vivo.
      RESULTS: TGF-beta induced Foxp3 expression in thymic CD4+CD25+ cells and
      converted them to CD25+ Tregs. The converted Tregs expressed high levels of CD25,
      whereas the non-suppressive CD4+ T cells from the control cultures expressed
      CD25(low). CD28-/- thymic CD4+CD25+ cells showed transit lower levels of Foxp3
      upon TCR and TGF-beta stimulation early in culture, but the defect in Foxp3
      expression was restored to normal levels after 60-72 hr. Consequently, TGF-beta
      converted CD28-/- CD25+ cells to CD25+ Tregs that were indistinguishable from
      those of the wildtype mice. However, the total number of TGF-beta converted CD28
      /- Tregs was significantly lower than that of wildtype mice. In vivo, TGF-beta
      converted CD28-/- CD25+ Tregs were less viable than those from the wildtype mice.
      Importantly, TGF-beta induced alloantigen specific CD4+CD25+ Tregs from thymic
      CD25-SP cells which also required CD28 to maintain their survival. CONCLUSIONS:
      TGF-beta and TCR co-stimulation converts thymic CD4+CD25+ T cells into CD4+CD25+
      Tregs by inducing Foxp3, and the contribution of CD28 stimulation to this process
      is mainly through maintaining survival of the induced Tregs.

PMID- 17038913
TI  - Rabbit antithymocyte globulin inhibits monocyte-derived dendritic cells
      maturation in vitro and polarizes monocyte-derived dendritic cells towards
      tolerogenic dendritic cells expressing indoleamine 2,3-dioxygenase.
AB  - BACKGROUND: Rabbit antithymocyte globulin (rATG) is a polyclonal mixture of
      immunoglobulin (Ig) G. It is used to prevent graft rejection and also graft
      versus host disease after transplantation. Its effect on lymphocyte function has
      been widely studied. Dendritic cells are central actors of the immune system. As
      antigen presenting cells, they are able to initiate, stimulate, and modulate
      immune responses. METHODS: In this study, we investigated rATG effects on in
      vitro differentiation and maturation of monocyte-derived dendritic cells (Mo
      DCs). RESULTS: rATG inhibited maturation of immature Mo-DCs and allowed the
      generation of dendritic cells expressing ILT-3, CD123, CCR6 but not CCR7 and
      producing Indoleamine 2,3-dioxygenase mRNA as well as interferon-alpha.
      CONCLUSION: rATG polarizes in vitro Mo-DCs towards tolerogenic dendritic cells.

PMID- 17038914
TI  - Direct and rapid modification of a porcine xenoantigen gene (GGTA1).
AB  - The ability to modify animal genomes rapidly at a specific locus would be
      valuable both for research purposes and in the development of animals suitable
      for xenotransplantation. In a proof-of-concept study, we used a unique, homology
      dependent strand transferase protein called drosophila recombination-associated
      protein (DRAP) and DNA oligonucleotides to modify the porcine gene encoding alpha
      1,3 galactosyl transferase (GGTA1). This gene is responsible for generating
      xenotransplantation antigens resulting in hyperacute rejection. Pronuclear
      injection of DRAP and mutant oligonucleotides yielded piglets with heritable,
      modified alleles of GGTA1 in a direct, rapid and efficient manner. Cells derived
      from these piglets had markedly reduced alpha 1,3 galactosyl sugar epitopes. The
      simplicity of this method should permit rapid sequential or simultaneous
      modification of the various genes encoding or producing antigens that impose
      limits on xenotransplantation as they are discovered.

PMID- 17038915
TI  - A prospective survey of human herpesvirus-6 primary infection in solid organ
      transplant recipients.
AB  - Human herpesvirus 6 (HHV-6) infection is potentially life-threatening to
      immunosuppressed patients. There is a lack of information regarding the risk and
      the clinical manifestations of primary HHV-6 infection in solid-organ transplant
      recipients. We prospectively evaluated patients undergoing solid organ
      transplantation with negative immunoglobulin (Ig) G antibodies against HHV-6 by
      means of HHV-6 quantitative polymerase chain reaction. Among 193 recipients,
      seven were HHV-6 seronegative (prevalence 3.6%). We detected a positive HHV-6
      viral load in only one patient, and four patients seroconverted after one year
      posttransplantation. The patient with a positive HHV-6 viral load developed
      cholestatic hepatitis without fever and did not experience severe end-organ
      disease. In conclusion, our findings show a low incidence of symptomatic primary
      HHV-6 infection among seronegative solid-organ transplant recipients.

PMID- 17038916
TI  - Human islet isolation outcomes from pancreata preserved with Histidine-Tryptophan
      Ketoglutarate versus University of Wisconsin solution.
AB  - This study was designed to compare Histadine-Tryptophan-Ketogluterate (HTK) with
      University of Wisconsin (UW) solution. Pancreata from extended criteria donors
      were flushed and transported with HTK (n=41) or UW (n=45). Isolation outcomes
      were determined by islet yields, viability and in vitro and in vivo function.
      Final yields were similar between two groups (HTK: 383,085 vs. UW: 328,514 EIN,
      P=0.14). In the HTK group, 63.4% (26/41) of isolations resulted in a yield of
      over 300,000, and in the UW group this was achieved in 46.7% (21/45; P=0.12).
      Viability results were similar (HTK: 82.9 vs. UW: 82.7%, P=0.93). Stimulation
      index in the HTK and UW groups were comparable (5.28 vs. 4.91, P=0.62). Ten out
      of 41 islet preparations in HTK and 4 of 45 in UW group were suitable for
      clinical transplantation (P=0.05). Our study shows HTK is equivalent to UW
      solution in the preservation of pancreata for islet isolation.

PMID- 17038917
TI  - BK viral genotype identification of a renal donor and their recipient pair.

PMID- 17038918
TI  - Hypercalcemia related to immune reconstitution in organ transplant recipients
      with granulomatous opportunistic infections.

PMID- 17038919
TI  - The future challenge in the MELD era: how to match extended-use donors and sick
      recipients.

PMID- 17038920
TI  - Late humoral rejection in a compliant ABO-compatible liver transplant recipient.

PMID- 17038921
TI  - The treatment of acute osteomyelitis by drainage and rest. 1927.

PMID- 17038923
TI  - An obscure affection of the hip joint. 1910.

PMID- 17038924
TI  - On a particular form of pseudo-coxalgia associated with a characteristic
      deformity of the upper end of the femur. 1910.

PMID- 17038925
TI  - Concerning arthritis deformans juvenilis. 1910.

PMID- 17038928
TI  - Temporomandibular joint cyst presenting as trigeminal neuropathy and middle fossa
      mass: case report.
AB  - OBJECTIVE: We describe the case of a temporomandibular joint cyst eroding into
      the middle fossa, initially causing compression of the trigeminal nerve and
      trigeminal neuropathy, and ultimately causing destruction of the second division
      of the nerve with facial numbness. CLINICAL PRESENTATION: A 50-year-old woman
      with rheumatoid arthritis on prednisone developed right-sided, initially
      lancinating facial pain that ultimately became dull in nature in the maxillary
      division of the trigeminal nerve. This change in pain was associated with the
      development of numbness in the same distribution. The facial pain gradually
      resolved, but the facial numbness persisted. Imaging revealed a heterogeneously
      enhancing mass in the middle fossa lateral to Meckel's cave. INTERVENTION: During
      surgery, the dura was elevated, and a smooth, firm lesion with several thinly
      encapsulated, cystic areas containing viscous, white fluid was identified. The
      mass had eroded through the floor of the middle cranial fossa. The thick, fibrous
      capsule was freed from the bone edges and was sectioned sharply extracranially.
      Pathological evaluation was consistent with a cyst originating from the
      temporomandibular joint. CONCLUSION: Extracranial mass lesions involving the
      middle fossa structures are uncommon and typically arise from the parotid gland.
      This case represents the first example of a middle fossa mass originating from an
      abnormal temporomandibular joint and a unique cause of trigeminal neuropathy.
      After excision, there has been no recurrence after 2 years of follow-up.

PMID- 17038929
TI  - Solitary fibrous tumor arising from Cranial Nerve VI in the prepontine cistern:
      case report and review of a tumor subpopulation mimicking schwannoma.
AB  - OBJECTIVE: The authors present a report of a solitary fibrous tumor (SFT) arising
      from the intradural component of the VIth cranial nerve as it travels through the
      prepontine cistern. SFTs of the central nervous system are extremely rare
      entities that clinically masquerade as dural-based lesions, such as meningiomas
      or hemangiopericytomas. Because of their infrequency and clinical similarity to
      other central nervous system (CNS) lesions, diagnosis is largely dependent on
      pathological features. In this study, the authors define a subpopulation of SFTs
      that seem to arise directly from nerve, rather than meninges, and clinically
      mimic the appearance of a schwannoma. CLINICAL PRESENTATION: The patient was a 29
      year-old woman with a several-month history of progressive right arm and leg
      numbness and mild hemiparesis, with the development of diplopia 2 weeks before
      admission. Outside imaging revealed a 3.9-cm mass in the prepontine cistern with
      extension into Meckel's cave and the cavernous sinus, resulting in significant
      brainstem compression. INTERVENTION: The patient underwent preoperative
      angiography with embolization of feeding vessels off of the left
      meningohypophyseal trunk. The patient was then taken to the operating room by a
      combined neurosurgical and ear, nose, and throat team, where the patient
      underwent a retrolabyrinthine/subtemporal craniotomy for tumor resection. During
      resection of the prepontine component, the tumor was identified as originating
      from the left Cranial Nerve VI as it traversed through the prepontine cistern.
      Resection of the tumor component involving the cavernous sinus and Meckel's cave
      was deferred for follow-up treatment with intensity-modulated radiation therapy.
      Pathological examination revealed tissue consistent with the diagnosis of SFT.
      CONCLUSION: SFTs involving the CNS are rare entities that are almost always
      diagnosed after tissue is obtained because of their clinical and radiographic
      similarity to meningiomas. This patient had an SFT masquerading as a VIth cranial
      nerve schwannoma. Although the natural history of SFTs in the CNS is not
      completely understood, correct diagnosis is important, given the rate of
      recurrence found in the more common pleural-based SFT and examples of CNS SFTs
      with malignant features.

PMID- 17038930
TI  - Utility of preoperative magnetic resonance imaging myelography for identifying
      dural defects in patients with spinal extradural arachnoid cysts: case report.
AB  - OBJECTIVE: Preoperative magnetic resonance imaging (MRI) myelography scans
      demonstrated a dural defect in a 50-year-old man with an epidural arachnoid cyst
      who had a 29-year history of untreated weakness and numbness both lower limbs.
      METHODS: MRI scans showed a dorsal intraspinal extradural cystic lesion at the
      level from Th11 to L1. Although preoperative cine-MRI scans failed to display the
      dural defect, an MRI myelography scan showed cerebrospinal fluid in the
      subarachnoid space containing a cyst. RESULTS: The site of shunting between the
      subarachnoid space and the cyst was visualized as a pulsating flow void to the
      right of Th12. We removed the cyst wall and closed the dural defect via
      laminectomy. CONCLUSION: Because the preoperative MRI myelography scan correctly
      identified the existence and location of the dural defect, we conclude that MRI
      myelography is helpful for detecting dural defects in patients with epidural
      arachnoid cysts.

PMID- 17038931
TI  - Intradural spinal Wilm's tumor metastasis: case report.
AB  - OBJECTIVE: Wilm's tumor metastasis to the central nervous system (especially the
      spine) is rare. We present a case of a lumbosacral intradural drop metastasis in
      a male child with a remote history of intracerebral Wilm's tumor metastases.
      CLINICAL PRESENTATION: A 7-year-old boy with known metastatic Wilm's tumor was
      discovered to have left frontal and parietal metastases. He subsequently
      underwent craniotomy and gross total resections of those lesions. Four years
      later, he developed low back pain and lower extremity weakness and was found to
      have an intradural lumbosacral lesion without intracranial recurrence.
      INTERVENTION: The patient underwent lumbar laminectomy for resection of the
      intradural lesion. The tumor was found to be in the subarachnoid space and
      displaced the nerve roots of the cauda equina to the periphery of the thecal sac.
      The nerve roots were matted and encased within tumor tissue, thereby limiting the
      surgery to biopsy only. Postoperatively, the patient received radiation to the
      lesion. Unfortunately, follow-up imaging 4 months later revealed little tumor
      regression, and the patient's neurological condition did not improve
      significantly. CONCLUSION: Spinal intradural Wilm's tumor metastases are rare.
      This is the only reported case in the literature of a probable drop metastasis
      from an intracerebral source. Although the optimal treatment for intra- or
      extradural Wilm's tumor spine metastases is not known, our patient did not make
      significant neurological improvement with radiation therapy.

PMID- 17038936
TI  - Psychosurgery: avoiding an ethical redux while advancing a therapeutic future.

PMID- 17038937
TI  - Education and neuromodulation for psychiatric disorders: a perspective for
      practitioners.

PMID- 17038938
TI  - Surgery of the mind and mood: a mosaic of issues in time and evolution.
AB  - The prevalence and economic burden of neuropsychiatric disease are enormous. The
      surgical treatment of these psychiatric disorders, although potentially valuable,
      remains one of the most controversial subjects in medicine, as its concept and
      potential reality raises thorny issues of moral, ethical, and socioeconomic
      consequence. This article traces the roots of concept and surgical efforts in
      this turbulent area from prehistory to the 21st century. The details of the late
      19th and 20th century evolution of approaches to the problem of intractable
      psychiatric diseases with scrutiny of the persona and contributions of the key
      individuals Gottlieb Burckhardt, John Fulton, Egas Moniz, Walter Freeman, James
      Watts, and William Scoville are presented as a foundation for the later, more
      logically refined approaches of Lars Leksell, Peter Lindstrom, Geoffrey Knight,
      Jean Talaraich, and Desmond Kelly. These refinements, characterized by
      progressive minimalism and founded on a better comprehension of underlying
      pathways of normal function and disease states, have been further explored with
      recent advances in imaging, which have allowed the emergence of less invasive and
      technology driven non-ablative surgical directives toward these problematical
      disorders of mind and mood. The application of therapies based on imaging
      comprehension of pathway and relay abnormalities, along with explorations of the
      notion of surgical minimalism, promise to serve as an impetus for revival of an
      active surgical effort in this key global health and socioeconomic problem.
      Eventual coupling of cellular and molecular biology and nanotechnology with
      surgical enterprise is on the horizon.

PMID- 17038939
TI  - Synthetic nerve guide implants in humans: a comprehensive survey.
AB  - OBJECTIVE: Lesions of the peripheral nervous system result in the loss of sensory
      and motor function and may in addition be accompanied by severe neuropathic
      syndromes originating from aberrant axonal regrowth. The transplantation of
      autologous nerve grafts represents the current "gold standard" during
      reconstructive surgery, despite obvious side effects. Depending on the demands of
      the lesion site, various donor nerves may be used for grafting (e.g., the sural,
      saphenous), sacrificing native functions in their target areas. Recently, several
      synthetic nerve guide implants have been introduced and approved for clinical use
      to replace autologous transplants. This alternative therapy is based on
      pioneering studies with experimental nerve guides. METHODS: We present a
      comprehensive review of all published human studies involving synthetic nerve
      guides. RESULTS: Data from some 300 patients suggest that for short nerve defects
      of a few centimeters, resorbable implants provide promising results, whereas a
      number of late compression syndromes have been documented for nonresorbable
      implants. CONCLUSIONS: To treat longer defects, further implant development is
      needed, a goal that could be achieved, for example, by more closely imitating the
      intact nerve architecture and regulatory cell-cell interactions.

PMID- 17038940
TI  - The neurosurgical workforce in North America: a critical review of gender issues.
AB  - OBJECTIVE: The role of women in Western society has changed dramatically in the
      past several decades. Despite this, many gender disparities still exist for
      professionals in the health care sector. In neurosurgery, a disproportionately
      small percentage of the workforce in the United States and Canada is female.
      These figures are lower than most reported in other medical specialties. This
      review critically examines factors that may be influencing women's ability to
      advance in demanding subspecialties such as neurosurgery. METHODS: The literature
      on women in medicine, and surgery in particular, were reviewed to identify
      different issues facing women currently in practice in neurosurgery. In addition,
      the concerns of prospective trainees were examined. RESULTS: There remain many
      challenges for women entering neurosurgery, including unique lifestyle concerns,
      limited mentorship, out-dated career programs, and deep-seeded societal beliefs.
      Discrimination and harassment are also contributing factors. CONCLUSION: If
      neurosurgery is to continue to progress as a subspecialty, the issue of gender
      inequality needs to be scrutinized more closely. Innovative programs must be
      developed to meet the needs of current female faculty members and to ensure
      attracting the brightest individuals of both genders into a career in
      neurosurgery.

PMID- 17038941
TI  - Self-assessment in neurological surgery: the SANS wired white paper.
AB  - OBJECTIVE: Periodic self-assessment is an important component of postgraduate
      medical education and certification. The Self-assessment in Neurological Surgery
      (SANS) examination has a history of usefulness for neurosurgical written and oral
      board examination preparation. The SANS Wired test represents a recreation of the
      original SANS test using an Internet-based platform. Advanced functionality and
      contemporary content have been added to meet the increasing requirements for
      demonstration of lifelong learning and self-assessment as part of the Maintenance
      of Certification (MOC) process. METHODS: A needs assessment was performed before
      the development of SANS Wired. Postexamination surveys for users obtaining
      continuing medical education credit were analyzed for user satisfaction with the
      platform and content. Test-item performance metrics were analyzed based on first
      attempt responses. The economic value of SANS Wired as a component of the
      mandatory MOC process was evaluated. RESULTS: The needs assessment identified a
      deficiency of available content and mechanisms for neurosurgery-specific self
      assessment. As of October 15, 2005, a total of 588 individuals had subscribed to
      SANS Wired (28 institutional licenses accounted for 229 users). Eighty-eight post
      test surveys were analyzed for user satisfaction. Ninety-four percent of
      responses indicated that learning objectives had been met. Initial performance
      metrics show an average point-biserial discrimination index of +0.18 for all test
      items. CONCLUSION: The SANS Wired system seems to be an effective platform for
      neurosurgical self-assessment and is acceptable to users. The system satisfies,
      in part, two of the four required components of MOC, namely, periodic self
      assessment and demonstration of cognitive expertise. It is endorsed by the
      American Board of Neurological Surgeons for MOC.

PMID- 17038942
TI  - Dynamics of intraventricular hemorrhage in patients with spontaneous
      intracerebral hemorrhage: risk factors, clinical impact, and effect of hemostatic
      therapy with recombinant activated factor VII.
AB  - OBJECTIVE: To evaluate predictors of intraventricular hemorrhage (IVH) and IVH
      growth, impact of IVH growth on outcome, and impact of recombinant activated
      factor VII (rFVIIa) in patients with intracerebral hemorrhage (ICH). METHODS: We
      analyzed 374 patients out of 399 who were randomized to rFVIIa (40, 80, or 160
      mug/kg) or placebo for ICH (diagnosed within 3 h of symptoms). Risk factors for
      IVH growth (>2 ml increase in IVH volume at 24 h), and death or severe disability
      (modified Rankin scale score 4-6) at 3 months were identified (logistic
      regression). RESULTS: IVH was present in 38% (n = 141) of patients at baseline
      and 45% (n = 169) by 24 hours. IVH growth, by 24 hours, occurred in 17 and 10% of
      placebo- and rFVIIa-treated patients, respectively (P = 0.037). Risk factors for
      IVH growth included baseline mean arterial pressure greater than 120 mmHg, larger
      baseline ICH volume, IVH present at baseline, shorter time from symptom onset to
      baseline computed tomographic scan, and treatment (rFVIIa versus placebo) (all, P
      < or = 0.037). Predictors of death or severe disability included older age, lower
      baseline Glasgow Coma Score, larger baseline ICH volume, IVH growth greater than
      2 ml, IVH present at baseline or 24 hours, and treatment (rFVIIa versus placebo)
      (all, P < or = 0.0405). CONCLUSION: Presence of IVH at any time and early IVH
      growth worsen clinical outcome and increase mortality. Elevated mean arterial
      pressure at baseline may be a modifiable risk factor for IVH growth. Beneficial
      effects of rFVIIa on ICH outcome may be mediated, at least in part, by reducing
      IVH growth.

PMID- 17038943
TI  - Higher hemoglobin is associated with less cerebral infarction, poor outcome, and
      death after subarachnoid hemorrhage.
AB  - OBJECTIVE: Higher-goal hemoglobin (hgb) and more packed red blood cell
      transfusions lead to worse outcomes in general critical care patients. There are
      few data on hgb, transfusion, and outcomes after aneurysmal subarachnoid
      hemorrhage (SAH). METHODS: We reviewed the daily hgb levels of 103 patients with
      aneurysmal SAH. Cerebral infarction was diagnosed by computed tomographic scan.
      We corrected for Hunt and Hess grade, age, and angiographic vasospasm in
      multivariate models. RESULTS: Of 103 patients, the mean age was 55.3 +/- 14.5
      years, 63% were women, and 29% were Hunt and Hess Grades 4 and 5; hgb values
      steadily declined from 12.6 +/- 1.7 g/dl the day of SAH to 10.4 +/- 1.2 g/dl by
      Day 14. Patients who died had lower hgb than survivors on Days 0, 1, 2, 4, 6, 10,
      11, and 12 (P < or = 0.05). Higher mean hgb was associated with reduced odds of
      poor outcome (odds ratio, 0.57 per g/dl; 95% confidence interval [CI], 0.38-0.87;
      P = 0.008) after correcting for Hunt and Hess grade, age, and vasospasm; results
      for hgb on Days 0 and 1 were similar. Higher Day 0 (odds ratio, 0.7 per g/dl; 95%
      CI, 0.5-0.99; P = 0.05) and mean hgb (odds ratio, 0.57 per g/dl; 95% CI, 0.38
      0.87; P = 0.009) predicted a lower risk of cerebral infarction independent of
      vasospasm. There were no associations between hgb and other prognostic variables.
      CONCLUSION: We found that SAH patients with higher initial and mean hgb values
      had improved outcomes. Higher hgb in SAH patients may be beneficial. The efficacy
      and safety of blood transfusions to increase hgb in patients with SAH may warrant
      further study.

PMID- 17038944
TI  - Cognitive functioning in patients with cerebral aneurysms measured with the mini
      mental state examination and the telephone interview for cognitive status.
AB  - BACKGROUND: Clinicians and researchers use brief instruments, such as the Mini
      Mental State Examination (MMSE) and the Telephone Interview for Cognitive Status
      (TICS), to measure cognitive functioning in patients with cerebral aneurysms.
      MMSE and TICS scores are often dichotomized to classify patients as cognitively
      impaired or not. Frequently, after an initial MMSE face-to-face evaluation, the
      TICS is used for follow-up assessments by telephone. METHODS: A cross-sectional
      cohort of patients with cerebral aneurysms completed the MMSE at baseline and the
      MMSE or TICS at the 12-month follow-up examination. Multivariate logistic
      regression adjusting for demographics was used to model cognitive impairment.
      MMSE and TICS results were compared using the MMSE as the "gold standard."
      RESULTS: Eleven out of 171 (6%) patients had baseline MMSE scores less than 24,
      indicating cognitive impairment. Multivariate analysis showed that a history of
      subarachnoid hemorrhage was associated with cognitive impairment measured with
      the MMSE (odds ratio, 13.9; P = 0.021; C statistic = 0.87); there was no
      relationship between subarachnoid hemorrhage or treatment and TICS cognitive
      impairment (i.e., score < 27). In patients without recent or interim invasive
      interventions that might affect cognition (n = 65), raw baseline MMSE and 12
      month TICS scores had fair correlations (r = 0.30, P = 0.015); however,
      dichotomized scores had poor agreement, and TICS sensitivity and positive
      predictive value was 0% compared with the MMSE. CONCLUSION: The MMSE may be more
      sensitive than the TICS to the effects of subarachnoid hemorrhage on cognitive
      functioning. Raw MMSE and TICS scores are well correlated, but dichotomized MMSE
      and TICS scores are probably not interchangeable in this patient population.

PMID- 17038945
TI  - Use of heparin-coated stents in neurovascular interventional procedures:
      preliminary experience with 10 patients.
AB  - OBJECTIVE: Currently, there is minimal published data on the use of heparin
      coated stents in the neurovasculature; however, these stents have a proven
      clinical record in the treatment of coronary disease. This article details our
      experience with the safety and technical aspects of stent deployment in the first
      10 patients who had heparin-coated stents placed in the intracranial and cervical
      vasculature and the preliminary follow-up in most cases. METHODS: We
      retrospectively reviewed the clinical history, intra- and periprocedural data,
      and imaging for the patients who received heparin-coated stents in the cervical
      and intracranial vasculature for cerebrovascular disease between October 2002 and
      October 2003. RESULTS: Thirteen heparin-coated stents were placed in 10 patients.
      Seven out of the 10 patients had heparin-coated stents placed in the posterior
      circulation; the remaining three patients had stents placed in the anterior
      circulation. Four patients had stents placed intracranially. There was no acute
      or subacute in-stent thrombosis and no procedure-related complications. Follow-up
      was performed on most patients, with no clinical symptoms attributable to
      restenosis in any patient. CONCLUSION: This small series suggests that heparin
      coated stents are safe for use in the treatment of cervical and intracranial
      atherosclerotic disease. Longer-term follow-up is needed to study the heparin
      coating effect on in-stent restenosis rates and to assess the long-term
      durability and clinical efficacy of this stent. The use of drug-coated stents in
      the cerebrovascular circulation is an area that warrants further investigation.

PMID- 17038946
TI  - A randomized trial of synthetic patch versus direct primary closure in carotid
      endarterectomy.
AB  - OBJECTIVE: To define whether or not direct microscopic closure with or without
      the use of a vascular patch is advantageous in terms of clinical outcome and late
      vessel occlusion rates after microsurgical carotid endarterectomy. METHODS: Three
      hundred thirty-eight elective carotid endarterectomies in 315 patients were
      randomized to direct arteriotomy or closure with a polyester collagen-coated
      vascular patch. Ten procedures did not follow the randomization process because
      of technical difficulties and were excluded. Vessel patency (duplex ultrasound)
      and outcome were assessed during and immediately after surgery and at 4 and 12
      months after surgery. RESULTS: Four-month ultrasound assessment (n = 321)
      identified five occluded vessels: two in the patch group (n = 149) and three in
      the direct closure group (n = 172). Six patients in the patch group had died or
      were significantly disabled at 4 months, compared with five in the direct closure
      group. At the 12-month assessment (n = 313), eight vessels had occluded: five
      from the patched group (n = 146) and three from the direct closure group (n =
      167). Eight patients in the patch group had died or were significantly disabled,
      compared with four in the direct closure group. No statistically significant
      difference between the two groups in terms of vessel occlusion, morbidity, or
      mortality was seen (P > 0.1). CONCLUSION: No difference in vessel patency and
      clinical outcome has been identified after microscopic patch angioplasty and
      direct arteriotomy repair. The authors conclude that there is no benefit from the
      routine use of patch angioplasty in microscopic carotid endarterectomy.

PMID- 17038947
TI  - Unilaterally symptomatic moyamoya disease in children: long-term follow-up of 20
      patients.
AB  - OBJECTIVE: In unilaterally symptomatic moyamoya disease in children, it remains
      controversial whether bypass surgery should be performed on the asymptomatic side
      along with on the symptomatic side. We aimed to verify the validity of our
      strategy of only performing bypass surgery on the symptomatic side. METHODS:
      Among 91 pediatric patients with moyamoya disease who underwent bypass surgery in
      our department between 1980 and 2004, 20 with unilateral ischemic symptoms who
      were followed for more than 60 months were analyzed in the present study.
      Initially, we only performed bypass surgery on the symptomatic side for all 20
      patients. Among these 20 patients, five developed frequent transient ischemic
      attacks in the initially asymptomatic side and underwent a second bypass surgery
      on that side (Group A), eight developed sporadic transient ischemic attacks and
      were followed up without surgery (Group B), and seven did not experience any
      ischemic symptoms on the asymptomatic side (Group C). RESULTS: In total, 18
      patients progressed well without cerebral infarctions after their last surgery,
      although some showed deterioration of angiographic stenosis and a transient
      decrease in the regional cerebral blood flow or cerebral perfusion reserve. One
      patient in Group A had an intraventricular hemorrhage 5 years after the second
      operation, and one in Group B had a minor stroke on the initially asymptomatic
      side. CONCLUSION: In unilaterally symptomatic moyamoya disease, bypass surgery
      for the asymptomatic side can be delayed until the development of ischemic
      symptoms, such as frequent transient ischemic attacks.

PMID- 17038948
TI  - Ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus
      increases midbrain size: a potential mechanism for gait improvement.
AB  - OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a
      classic clinical triad of symptoms, including dementia, urinary incontinence, and
      gait disturbance. Recent work has demonstrated that the maximal midbrain
      anteroposterior (AP) diameter is significantly smaller in patients with INPH than
      in healthy, age-matched controls. The current study was undertaken to determine
      the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH
      patients. METHODS: Twelve consecutive INPH patients undergoing
      ventriculoperitoneal shunt placement with pre- and postoperative computed
      tomographic scans at the Columbia University Medical Center were enrolled. Each
      patient's pre- and postoperative maximum AP and left-to-right diameters of the
      midbrain at the pontomesencephalic junction were independently measured in a
      blinded fashion by two of the authors. The average value of each dimension was
      computed by calculating the mean values of the measurements of the two observers.
      RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm;
      postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter
      (preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029)
      increased from pre- to postoperative imaging. The approximate cross-sectional
      area determined as the product of AP and left-to-right diameters also increased
      from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm;
      postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study
      provides supportive evidence that midbrain cytoarchitecture may play a role in
      the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH
      patients.

PMID- 17038949
TI  - Postoperative pain management after craniotomy: evaluation and cost analysis.
AB  - OBJECTIVE: Patients undergoing craniotomies have traditionally received opiates
      for the management of their postoperative pain. The use of narcotic pain
      medications can be costly, can decrease early walking, can lengthen hospital
      stay, and can alter a patient's neurological examination results. The use of
      alternative pain medications such as cyclooxygenase-2 (COX-2) inhibitors may
      benefit patients by resolving many of these issues. Compared with traditional
      nonsteroidal anti-inflammatory drugs, these anti-inflammatory medications may be
      used safely in neurosurgical patients because of their selective inhibition of
      the COX-2 enzyme, which avoids the platelet dysfunction caused by other
      nonsteroidal anti-inflammatory drugs. METHODS: A randomized, single-blinded
      prospective study was used to evaluate the efficacy of alternative pain
      management strategies for patients who have undergone craniotomy. Twenty-seven
      patients were randomly assigned to a control group (n = 13) receiving narcotics
      alone or an experimental group (n = 14) receiving a COX-2 inhibitor in addition
      to narcotic pain medications. RESULTS: The narcotics group was noted to have
      statistically significantly higher visual analog scale scores, increased length
      of stay, and increased narcotic use compared with the COX-2 group. The narcotics
      group also had increased hospitalization costs when compared with the COX-2
      group. CONCLUSION: The use of scheduled atypical analgesics, such as COX-2
      inhibitors, in addition to narcotics for the management of postoperative pain
      after craniotomy may provide better pain control, may decrease side effects
      associated with narcotic pain medications, may encourage earlier walking, and may
      reduce total hospitalization costs.

PMID- 17038950
TI  - Accessory nerve to suprascapular nerve transfer to restore shoulder exorotation
      in otherwise spontaneously recovered obstetric brachial plexus lesions.
AB  - OBJECTIVE: A systematic follow-up of infants with an obstetric brachial plexus
      lesion of C5 and C6 or the superior trunk showing satisfactory spontaneous
      recovery of shoulder and arm function except for voluntary shoulder exorotation,
      who underwent an accessory to suprascapular nerve transfer to improve active
      shoulder exorotation, to evaluate for functional recovery, and to understand why
      other superior trunk functions spontaneously recover in contrast with
      exorotation. METHODS: In 54 children, an accessory to suprascapular nerve
      transfer was performed as a separate procedure at a mean age of 21.7 months.
      Follow-up examinations were conducted before and at 4, 8, 12, 24, and 36 months
      after operation and included scoring of shoulder exorotation and abduction.
      Intraoperative reactivity of spinatus muscles and additional needle
      electromyographic responses were registered after electrostimulation of
      suprascapular nerves. Histological examination of suprascapular nerves was
      performed. Trophy of spinatus muscles was followed by magnetic resonance imaging
      scanning. The influence of perinatal variables and results of ancillary
      investigations on outcome were evaluated. RESULTS: Exorotation improved from 70
      degrees to functional levels exceeding 0 degrees, except in two patients.
      Abduction improved in 27 patients, with results of 90 degrees or more in 49
      patients. Electromyography at 4 months did not show signs of denervation in 39
      out of 40 patients. Intraoperative electrostimulation of suprascapular nerves
      elicited spinatus muscle reaction in 44 out of 48 patients. Histology of
      suprascapular nerves was normal. Preoperative magnetic resonance imaging scans
      showed only minor wasting of spinatus muscles in contrast with major wasting
      after successful operations. CONCLUSION: An accessory to suprascapular nerve
      transfer is effective to restore active exorotation when performed as the primary
      or a separate secondary procedure in children older than 10 months of age.
      Contradictory spontaneous recovery of other superior trunk functions and
      integrity of suprascapular nerves, as well as absence of spinatus muscle wasting
      direct to central nervous changes are possible main causes for the lack of
      exorotation.

PMID- 17038951
TI  - Microsurgical anatomy of the central retinal artery.
AB  - OBJECTIVE: To define the microsurgical anatomy of the central retinal artery
      (CRA) and to provide a guide to avoiding damage to it during surgery. METHODS:
      The anatomic characteristics of the CRA and small arteries distributed to the
      optic sheath were examined in 109 orbits. The origin, course, and site of entry
      of the artery into the optic sheath and the distance between the orbital apex and
      the site of entry into the sheath were examined. RESULTS: The CRAs originated
      directly from the intraorbital ophthalmic artery or in a common trunk with a
      posterior ciliary or a muscular branch. The CRAs most commonly originated on the
      inferomedial side of the ophthalmic artery an average of 8.4 mm distal to the
      orbital end of the optic canal. They penetrated the optic sheath near the
      junction of the middle and anterior thirds of the length of the intraorbital
      optic nerve an average of 18.6 mm distal to the optic canal. More than 70% of
      CRAs penetrated near the midline of the lower surface of the optic sheath, 21%
      entered the inferomedial surface, and 7% the inferolateral or lateral surface of
      the optic sheath. Only one CRA gave off a branch before penetrating the nerve.
      CONCLUSION: The CRA is at risk of being damaged or occluded during procedures
      involving a large part of the orbit. Procedures directed along the lower half of
      the proximal two-thirds of the optic sheath have the greatest risk of
      interrupting the artery.

PMID- 17038952
TI  - Optic strut as a radiographic landmark in evaluating neck location of a
      paraclinoid aneurysm.
AB  - OBJECTIVE: The optic strut (OS) is a candidate landmark in computed tomographic
      (CT) angiographic scans for the discrimination of intradural and
      extradural/intracavernous aneurysms involving the paraclinoid segment of the
      internal carotid artery. The goal of this study is to examine and confirm the
      qualifications of the OS as a landmark in CT angiographic scans for the
      preoperative evaluation of aneurysms in this region. METHODS: Seventeen
      consecutive patients with 18 unruptured paraclinoid aneurysms who underwent
      preoperative CT angiography scans and direct surgery between 1998 and 2005 were
      evaluated retrospectively. We focused on the relationships of the necks of
      aneurysms to the OS in CT angiographic scans and that of the necks to proximal
      dural rings during intraoperative examinations. RESULTS: Direct surgery revealed
      that 14 aneurysms, the necks of which were distal to the OS on CT angiographic
      scans, arose distal to the proximal dural rings. All aneurysms were clipped,
      except one exhibiting calcification of the neck. Three aneurysms, for which the
      neck was proximal to the OS on CT angiographic scans, revealed only a portion or
      nothing of their domes instead of their necks through the proximal dural rings
      after dissection of the distal dural rings. Dome coating with fibrin glue and a
      piece of muscle tissue or mere exploration was performed. Another aneurysm, of
      which the neck straddled the OS on CT angiographic scans, was found to arise
      across the proximal dural ring. Clipping of the neck was performed after
      dissection of the proximal dural ring. Of the source images of CT angiographic
      scans, the axial images were the most useful in evaluating the relationship of
      the neck of an aneurysm to the OS. CONCLUSION: On CT angiographic scans, the OS
      is a precise identification of the proximal dural ring that forms the superior
      border of the cavernous sinus. The aneurysms whose necks arise obviously distal
      to the OS on CT angiographic scans are able to be clipped without dissection of
      the proximal dural ring.

PMID- 17038953
TI  - Magnetic resonance imaging of the craniocervical junction at 3-T: observation of
      the accessory atlantoaxial ligaments.
AB  - OBJECTIVE: Instability of the craniocervical junction can cause neurological
      sequelae or pain. Stability of this region depends on extensive ligamentous
      support structures, most of which are well studied by magnetic resonance imaging
      (MRI) scanning. Although the contribution of the accessory atlantoaxial ligament
      to rotational stability has been described, this ligament has not been identified
      by imaging. Therefore, we investigated the imaging characteristics of this
      ligament and its relationship to the ligamentous complex of the craniocervical
      junction using the high resolution offered by 3-T MRI scans. METHODS: Ten healthy
      volunteers underwent MRI scanning at 3-T to determine the normal anatomy of this
      ligament. RESULTS: The atlantoaxial (C1-C2) segment of the ligament was
      identified in all 10 subjects bilaterally and symmetrically. Its mean dimensions
      were 2.8 x 1.8 mm. In four out of 10 subjects, the occipitoatlantal (C0-C1)
      segment was observed. At this level, the mean dimensions of the ligament were 1.6
      x 1.2 mm on the right and 1.8 x 1.4 mm on the left. Its size varied between the
      right and left sides. CONCLUSION: The accessory atlantoaxial ligament can be
      visualized using high-resolution MRI scans at 3-T. The ligament was most
      consistent and robust at C1-C2. The ligament may, therefore, contribute to
      rotational stability at this level. Future studies will determine the
      biomechanical importance of this ligament, especially in the setting of trauma.

PMID- 17038954
TI  - Caspase-3-dependent apoptosis in middle cerebral arteries in patients with
      moyamoya disease.
AB  - OBJECTIVE: Moyamoya disease (MMD) is a cerebrovascular occlusive disease
      characterized by progressive stenosis or occlusion at the distal ends of
      bilateral internal arteries. In MMD, a decreased number of medial smooth muscle
      cells in these vessels was previously reported. In this study focusing on the
      mechanism of remodeling in intracranial arterial walls of patients with MMD, we
      first collected tiny pieces of the wall of the middle cerebral artery (MCA) from
      patients with MMD and then analyzed them by immunohistochemical methods. METHODS:
      Ten patients underwent surgical procedures for the treatment of standard
      indications of MMD at Kyoto University Hospital. Specimens of MCA were obtained
      from these MMD patients during the surgical procedures. MCA samples were also
      obtained in the same way from control patients. The samples were analyzed by
      immunohistochemical methods. RESULTS: MCA specimens from MMD patients had a
      thinner media than control specimens. Immunoreactivities indicating single
      stranded DNA and cleaved caspase-3 were higher in MMD samples than in control
      ones and were located in the smooth muscle cells of the media. CONCLUSION: Our
      results indicate that apoptosis, as evidenced by activated caspase-3, occurred in
      the media of the MCA of MMD patients. Thus, the MCA specimens from MMD patients
      had thinner vascular walls than specimens from controls.

PMID- 17038955
TI  - Defective receptor expression and dendritic cell differentiation of monocytes in
      glioblastomas.
AB  - OBJECTIVE: Better characterization of the changes that occur in the circulating
      monocytes of patients with glioblastoma has become more important recently as
      monocyte-derived dendritic cells are used as adjuvants in the development of
      glioma vaccines. This study seeks to develop understanding of the phenotypic
      changes that occur in circulating monocytes of patients with intracranial cancer
      and to assess the ability of these cells to differentiate into mature dendritic
      cells. METHODS: Monocyte expression levels of HLA-ABC, HLA-DR, CD86, ICAM-1,
      TNFRII, and GMCSFR were compared between three cohorts: patients with
      intracranial glioblastoma (n = 15), patients with intracranial metastases (n =
      9), and a group of healthy controls (n = 10). Monocytes were then tested for
      their ability to differentiate into mature dentritic cells based on morphology,
      CD83 expression and high levels of co-stimulatory molecules. RESULTS:
      Comprehensive analysis of monocyte receptor expression demonstrated significantly
      reduced HLA-ABC, HLA-DR, CD86, ICAM-1, and TNFRII in patients with glioblastoma
      but not in patients with intracranial metastases compared with a group of healthy
      controls. GMCSFR expression was significantly reduced in both patients with
      glioblastoma and intracranial metastases. Additionally, the monocytes of patients
      with glioblastoma showed a reduced capacity to differentiate into mature
      dendritic cells as identified by CD83 expression, receptor expression, and
      morphology. CONCLUSION: Peripheral monocytes are phenotypically altered in the
      setting of glioblastoma and display a reduced functional capacity to
      differentiate into mature dendritic cells.

PMID- 17038956
TI  - Long-term histological and scanning electron microscopy results of endovascular
      and operative treatments of experimentally induced aneurysms in the rabbit.
AB  - OBJECTIVE: Treatment strategies of cerebral aneurysms include surgical clipping
      and endovascular therapies. To determine the long-term results of these
      therapeutic strategies, the vessel wall reaction close to the former aneurysm was
      studied according to the assumption that an intact endothelial layer over the
      former aneurysm neck constitutes complete vessel wall reconstruction and stable
      aneurysm obliteration. METHODS: Aneurysms were created in 40 rabbits by
      intraluminal elastase incubation of the common carotid artery. Five animals each
      were assigned to the following groups: untreated, porous stents, polyurethane
      covered stentgrafts, porous stents with subsequent coiling. Ten animals were
      treated with coils alone, 10 with clips. After 6 months, angiography, histology,
      and scanning electron microscopy was performed. RESULTS: Porous stents did not
      obliterate the aneurysm, whereas stentgrafts did; in-stent stenosis of up to 60%
      was present because of neointimal multilayer proliferation. After coiling, the
      aneurysm dome was occluded with fibrinous and collagenous material, whereas the
      aneurysm neck was not covered by an endothelial lining. Coil loops lay bare
      within the vessel, with fresh thrombus material on their surface. After clipping,
      a thin layer of endothelial lining bridging the two attached vessel walls was
      present, thereby completely obliterating the aneurysm and reconstructing the
      vessel wall. CONCLUSION: This study demonstrates complete and stable aneurysm
      obliteration with vessel wall reconstruction after clipping, a sufficient
      obliteration of the aneurysm dome using endovascular techniques, but a failed
      healing response of the aneurysm neck that might correlate to its associated
      higher risk of rebleed. Whether or not this is counterbalanced by the better
      immediate outcome after endovascular treatment remains a matter of debate.

PMID- 17038957
TI  - Safety and pharmacokinetics of sirolimus-eluting stents in the canine cerebral
      vasculature: 180 day assessment.
AB  - OBJECTIVE: We evaluated local and systemic pharmacokinetics and pharmacodynamics
      of sirolimus-eluting stents (SES) in canine cerebral vessels. METHODS: SES (1.5 x
      8 mm, 79 microg/479 microg sirolimus) and control stents (1.5 x 8 mm stainless
      steel with or without polymer) were implanted in canine basilar and ventral
      spinal arteries. Animals were sacrificed for local pharmacokinetic (36 animals at
      1, 3, 8, 30, 90, 180 days) and pharmacodynamic (60 animals at 3, 30, 90, 180
      days) assessment. RESULTS: Postrecovery adverse clinical events were not serious,
      requiring no unscheduled treatment. Histologically, brain and spinal cord
      sections revealed scattered microinfarcts and minimal gliosis consistent with
      postprocedure changes in all four stent-treatment groups. All stented vessels at
      all time points demonstrated good luminal patency with low injury and
      inflammation scores and no thrombosis of either stented or branch arteries.
      Endothelialization was complete in all stent groups by 30 days. Intimal smooth
      muscle cell scores were reduced in both SES groups at 30, 90, and 180 days.
      Systemic sirolimus levels peaked between 1 and 7 hours postimplant (maximum
      concentration, 1.2 +/- 1.47, 79 microg; 4.5 +/- 1.23 ng/ml, 479 microg), then
      declined rapidly to 1 ng/ml or less by 96 hours. Peak local tissue sirolimus
      levels were 41.5 ng/mg (79 microg) and 65 ng/mg (479 microg). CONCLUSION: SES in
      canine cerebral vessels were associated with good luminal patency to 180 days,
      with complete endothelialization and no evidence of acute thrombosis. This model
      has shown that SES deployed within the brain do not cause neurotoxicity during a
      180-day time course, even when exaggerated doses are used. The findings support
      the contention that SES are safe to use and maintain patency in cerebral vessels.

PMID- 17038958
TI  - The cure of folly or The operation for the stone by Hieronymus Bosch (C. 1450
      1516).

PMID- 17038961
TI  - Endoscopic fenestration of a symptomatic cavum septum pellucidum: technical case
      report.
AB  - OBJECTIVE: Cysts of the septum pellucidum (CSPs) may become symptomatic because
      of obstruction of cerebrospinal fluid flow, resulting in increased intracranial
      pressure and hydrocephalus requiring surgical intervention. Endoscopic
      fenestration may be the most effective and least invasive technique to treat this
      pathological condition. CLINICAL PRESENTATION: An 11-year-old boy sought
      treatment for frequent episodes of severe headache. On examination, he had
      papilledema. There was evidence on magnetic resonance imaging scans of a space
      occupying CSP with obstructive hydrocephalus. INTERVENTION: The endoscopic
      technique of fenestration of both lateral walls of an enlarged CSP via a left
      frontal approach under ultrasound guidance using a rigid endoscope was
      successful. After surgery, the patient became asymptomatic, his papilledema
      resolved, and magnetic resonance imaging scans demonstrated collapse of the walls
      of the CSP toward the midline. CONCLUSION: Neuroendoscopic fenestration should be
      strongly considered as the treatment of choice for symptomatic CSPs. This
      procedure alone can lead to complete resolution of clinical symptoms and
      hydrocephalus, can reduce the size of the CSP, and can obviate the need for an
      implantable cerebrospinal fluid shunt.

PMID- 17038962
TI  - Microsurgery in the removal of a large cerebral hydatid cyst: technical case
      report.
AB  - OBJECTIVE: Surgery is presently the mainstay in the treatment of cerebral hydatid
      cysts, but removal without perforation of the cyst wall is critical. The Dowling
      Orlando technique has been the main surgical choice for the intact removal of
      intracranial hydatid cysts. Dowling described his technique in 1929, well before
      the introduction of the microscope in neurosurgery. Using the operating
      microscope has not been reported in the removal of a large hydatid cyst. CLINICAL
      PRESENTATION: The case of a 16-year-old male with a large, right parieto
      occipital hydatid cyst is presented. INTERVENTION: In this case, surgery was
      greatly aided by the use of the microscope in the initial stage of the removal of
      the cyst. Cyst extraction during the delivery process was continued without the
      aid of the microscope. The cyst was successfully removed intact. CONCLUSION: The
      use of the magnification during the early part of the surgery of a hydatid cyst
      is extremely helpful because, at a crucial stage of the procedure, it prevents
      inadvertent damage of the very thin cyst wall and allows development of the
      critical surgical plane.

PMID- 17038963
TI  - An assessment of sites where persons go to meet sexual partners in St. James,
      Jamaica, using the PLACE method.
AB  - OBJECTIVE: The objective of this study was to assess sexual behavior of persons
      at risk of HIV infection. GOAL: The goal of this study was to identify sites
      where HIV prevention is needed. STUDY DESIGN: Customers at sites where persons
      meet new sex partners in St. James, Jamaica, were surveyed. RESULTS: Of 421
      sites, 282 men and 200 women (random sample, 23 sites) and 320 men and 265 women
      (special sample, 26 sites) were interviewed. Over one fourth of men and 14%
      (special) and 4% (random) of women had one or more new sex partners in the last 4
      weeks. Seventy-eight percent of men reported condom use at last sex with a new
      partner compared with 66% of women. Approximately 50% of respondents reported
      condom use at last sex with a regular partner. CONCLUSION: Sites at which people
      meet new sex partners were diverse with significant opportunities for prevention.
      Commercial and transactional sex are features at many sites.

PMID- 17038964
TI  - Measurement of microbicide acceptability among U.S. adolescent girls.
AB  - BACKGROUND AND OBJECTIVE: Topical microbicides will only be effective if they are
      acceptable to potential users. The purpose of this study is to develop a scale to
      evaluate characteristics and aspects of topical microbicides that are important
      to adolescent girls. STUDY DESIGN: Girls (n = 207) completed a questionnaire on
      perceptions of microbicide-like products. RESULTS: A principal components factor
      analysis with a varimax rotation produced a 6-factor solution. The mean factor
      scores suggested that girls saw the products positively. Age was positively
      correlated with "comparison to condoms" and "comfort while using" factor scores
      and inversely correlated with "negative impact on interpersonal relationships"
      factor score. Sexually transmitted infection (STI) history was related to higher
      scores on the "health benefits" and "pleasure" factors. Age, race/ethnicity, and
      STI history were not related to the other factor scores. CONCLUSION: The current
      scale shows promise in assessment of microbicide acceptability, and in general,
      girls expressed positive views about microbicides.

PMID- 17038967
TI  - Outcome measures and surgery for stress urinary incontinence.
AB  - A large number of surgical procedures to correct urinary stress incontinence in
      the female have been described. There has been wide variablility in reported
      success rates. This variablility is due to a number of factors. Papers published
      in 1997 that assess outcomes in the treatment of female stress urinary
      incontinence illustrate many of the current problems that exist with examining
      outcomes, including patient selection, modifications in technique, the definition
      of success, how success is measured and when the outcome is assessed.

PMID- 17038965
TI  - The efficacy of behavioral interventions in reducing HIV risk sex behaviors and
      incident sexually transmitted disease in black and Hispanic sexually transmitted
      disease clinic patients in the United States: a meta-analytic review.
AB  - OBJECTIVES: Interventions targeting sexually transmitted disease (STD) clinic
      patients provide an important opportunity to modify high-risk sex behaviors
      related to HIV/STD transmission. Identifying efficacious interventions for blacks
      and Hispanics is urgently needed because these 2 groups are disproportionately
      affected by the HIV/STD epidemics. GOAL: This meta-analysis evaluates the
      efficacy of behavioral interventions in reducing unprotected sex and incident STD
      among black and Hispanic STD clinic patients. STUDY DESIGN: Comprehensive
      searches, including electronic databases (1988-2004), hand searches of journals
      (January 2004 to June 2005), reference lists of articles, and contacts with
      researchers, identified 18 randomized, controlled trials meeting the selection
      criteria. RESULTS: Interventions significantly reduced unprotected sex (odds
      ratio [OR] = 0.77; 95% confidence interval [CI] = 0.68-0.87; 14 trials; N =
      11,590) and incident STD (OR = 0.85; 95% CI = 0.73-0.998; 13 trials; N = 16,172).
      CONCLUSIONS: Behavioral interventions provide an efficacious means of HIV/STD
      prevention for blacks and Hispanics who attend STD clinics.

PMID- 17038968
TI  - Results of behavioral treatment for urinary incontinence in women.
AB  - Recent research on pelvic muscle exercises, which are known to be effective in
      stress and mixed urinary incontinence, has demonstrated that this therapy has a
      durable effect. However, the mechanism that creates its efficacy remains unclear.
      Transvaginal electrical stimulation has been used to manage stress, urge and
      mixed urinary incontinence. Conflicting evidence exists concerning its efficacy
      in stress urinary incontinence, but its benefit to women with mixed and urge
      incontinence is well established.

PMID- 17038969
TI  - Laparoscopic correction of stress urinary incontinence.
AB  - The laparoscopic correction of stress urinary incontinence continues to be
      evaluated. Early results have been encouraging with cure/dry rates equivalent to
      those with traditional suspensions, but with shorter hospitalization and no
      significant morbidity. The approach continues to take longer in the operating
      room than traditional suspensions, although new innovations and refinements have
      shortened the time. We are still lacking long-term outcome data and well
      constructed prospective randomized trials. Cost effectiveness studies are also
      not consistent.

PMID- 17038970
TI  - Sacral neuromodulation in the treatment of the unstable bladder.
AB  - Sacral neuromodulation as a treatment for urge incontinence in patients with an
      unstable bladder is the subject of ongoing clinical studies. Although
      approximately 75% of the patients treated with a permanent sacral foramen
      electrode implant have experienced significant improvements, it is now also clear
      that there is an initial failure rate of about 25%. Recent studies have pointed
      out the importance of improved patient selection on the basis of sex differences,
      urodynamic parameters and psychological factors. Also, newer forms of test
      stimulation and permanent electrode implantation are being explored in an effort
      to improve on the present results.

PMID- 17038971
TI  - Use of intravesical capsaicin for urge urinary incontinence and irritative
      voiding syndromes.
AB  - Intravesical capsaicin has been used in the management of selected patients with
      urge urinary incontinence throughout this decade, but the past 12 months has seen
      considerable interest in this and related compounds. It is no coincidence that
      during the same period the capsaicin receptor was cloned and named the vanilloid
      receptor subtype 1 and the European dual centre study of intravesical capsaicin
      reported that overall 80% of patients derived some clinical benefit. In spite of
      this, ultrapotent capsaicin analogues such as resiniferatoxin, which also
      interact with the vanilloid receptor subtype 1, are being studied. Preliminary
      reports of the potential advantages of intravesical resiniferatoxin are beginning
      to emerge, and in the future drugs that manipulate the vanilloid receptor may
      become universally important in the management of neurogenic overactive bladders.

PMID- 17038974
TI  - Stones and bones: bone resorption and metabolism in stoneformers.
AB  - Abnormalities of bone metabolism and osteopenia (which may be progressive) are
      features of idiopathic calcium stone disease. This abnormal bone metabolism may
      be mediated by increased levels of, or responsiveness to, calcitriol or
      cytokines, including interleukin-1. Bone resorption may be reduced experimentally
      with bisphosphonates, but for clinical management an appropriate adjustment of
      dietary calcium intake may be the method of choice to ameliorate bone loss.

PMID- 17038973
TI  - Crystal-macromolecule interactions in urolithiasis: lessons from healthy
      biomineralization systems.
AB  - Recent advances in understanding the molecular level mechanisms that control
      biomineralization and organic-inorganic interactions in urolithiasis are
      reviewed, and the validity of drawing parallels between them are considered. The
      multifunctional nature of many biomineralization molecules, particularly
      proteins, and the different roles they play in and out of solution suggest
      avenues for resolving the apparent paradox that urinary macromolecules have been
      observed both to inhibit and to promote stone formation.

PMID- 17038975
TI  - Molecular basis of inherited renal lithiasis.
AB  - Idiopathic calcium oxalate stone formation results from an interaction between
      genetic and environmental factors. Clearly identifiable risk factors for the
      disease that have a significant genetic influence are the excretions of calcium,
      oxalate and citrate. Candidate genes that may be responsible for these effects
      have been proposed. With the large-scale sequencing of the human genome and the
      identification of genetic polymorphisms, it is only a matter of time before these
      genes and the sequence differences within them that are associated with
      susceptibility to the disease are conclusively identified.

PMID- 17038976
TI  - Pathophysiology of idiopathic hypercalciuria: the current concept.
AB  - During past decades it became fashionable to address individual facets of
      idiopathic hypercalciuria selectively and independently in the laboratory, thus
      preparing for the almost impossible conciliation of these fragments in the
      future. In this review a unifying concept is presented, which places excessive
      meat protein intake at the centre of the scheme and links it to other facets of
      the phenotype of the disease, such as the genetic component of bone
      demineralization, fasting hypercalciuria and excessive production of 1,25
      dihydroxyvitamin D, as well as of various cytokines.

PMID- 17038977
TI  - An evidence-based approach to hypercalciuria: is it really necessary for the
      study of the role of calcium in urolithiasis?
AB  - An abnormally raised 24-h urinary excretion of calcium has long been regarded as
      a common feature of calcium stone disease. However, hypercalciuria can be defined
      only by reference to a range of values measured in a representative population of
      individuals who have never suffered from stone disease. To date, there have been
      significant flaws in all published studies reporting normal ranges for daily
      urinary calcium excretion. There is no doubt that additional, carefully performed
      and documented investigations need to be undertaken to establish what is truly
      abnormal for a given population; the persistent use of arbitrarily defined limits
      may be hindering rather than helping to unravel the role of calcium in the
      pathogenesis of calcium stones.

PMID- 17038978
TI  - Drug-induced urolithiasis.
AB  - Drugs can cause renal stone formation either by raising excretion rates of
      naturally occurring stone components or by directly precipitating within the
      urinary tract. In large series of analysed renal stones, the overall frequency of
      drug-induced urolithiasis is less than 0.5%. Five clinical presentations of drug
      induced crystallization in the kidneys can be recognized: asymptomatic
      crystalluria, symptomatic crystalluria; stone passage; obstructive uropathy and
      tubulointerstitial nephritis. In the current literature review, the protease
      inhibitors used for treatment of patients infected with the human
      immunodeficiency virus stand out as a new class of drugs that frequently causes
      crystallization within the urinary tract. The most widely used compound,
      indinavir, may lead to crystalluria and renal stone formation in up to 50% of
      patients, and occasionally also causes acute renal failure caused by obstructive
      uropathy or tubulointerstitial nephritis. On the other hand, ritonavir appears
      more often to induce (reversible) acute renal failure than stone formation.

PMID- 17039012
TI  - Current world literature.

PMID- 17039014
TI  - Surgery in advanced and metastatic renal cell carcinoma.
AB  - Curative surgery in more advanced renal cell carcinoma is limited to solitary
      metastases or regional disease. Response to systemic immunotherapy continues to
      be reported; however, most responses are limited and not durable. Only
      randomized, prospective clinical trials will prove the efficacy of systemic
      therapy.

PMID- 17039015
TI  - Prostate cancer: epidemiology and risk factors.
AB  - After years of rapid increase, the incidence of prostate cancer has begun to
      decline in certain areas in the USA. Although these temporal trends are
      consistent with the impact of screening, it still remains to be shown that early
      detection programmes and screening will result in a reduced mortality rate from
      this disease. A positive family history of prostate cancer has been established
      as an important risk factor, and recent research supports and points to the
      existence of a subgroup of prostate cancer families with a hereditary form of the
      disease. Diet is another well-known risk factor. Recently, it has become evident
      that nutritional factors might both prevent the progression of prostate cancer or
      induce it.

PMID- 17039016
TI  - Neoadjuvant therapy in localized prostate cancer before surgery and radiotherapy.
AB  - Neoadjuvant hormonal therapy brings the possibility of improving the results of
      radical treatment of clinically localized prostate cancer. While the advantages
      of this therapy combined with radiotherapy and cryosurgery are encouraging, as
      yet the positive effects of initial hormonal ablation before radical
      prostatectomy are still not proven.

PMID- 17039017
TI  - Brachytherapy in localized prostatic cancer: 100 years of radium.
AB  - Contemporary series of brachytherapy in localized prostate cancer show promising
      early results attributable to improved patient selection and technical
      refinements in treatment modalities. These innovations consist essentially of
      precise three-dimensional radioactive dose-distribution planning and source
      placement, thus solving the problem of possible under-dosage encountered in open
      brachytherapy.

PMID- 17039018
TI  - The clinical importance of free prostate-specific antigen (PSA).
AB  - The proportion of free prostate-specific antigen (PSA) in serum relative to total
      PSA (F/T) is lower in patients with prostate cancer than in those with elevated
      levels of PSA due to benign prostatic disease. When applied to early diagnosis
      and screening for prostate cancer, the proportion of free PSA can be used to
      reduce the number of false-positive results by 20-40%. The utility of F/T is
      better in men with a small prostate volume, i.e. in relatively young men, who are
      most likely to benefit from early diagnosis and treatment of prostate cancer. The
      concentrations of PSA and especially free PSA are affected by considerable intra
      individual variation and sample stability. Assay standardization is variable and
      it is therefore important to establish reference values for the methods used.
      Better control of these factors is likely to improve the diagnostic accuracy. The
      utility of determining free PSA can be improved by evaluating the combined impact
      of free and total PSA by logistic regression analysis or neural networks.

PMID- 17039019
TI  - Clinical implications of prostate-specific antigen (PSA).
AB  - Prostate-specific antigen(PSA) is currently the tumour marker of choice for
      prostatic carcinoma. This article examines the current literature on the
      application of PSA for cancer detection (concentrating on values of PSA in the
      normal and 'grey' areas of 2.5-10 ng/ml), in staging of the disease and
      prediction of treatment response. These areas in particular have been refined by
      the use of PSA indices (PSA density, velocity, age ranges) and the article
      focuses on the recent studies analysing their standing in clinical practice.

PMID- 17039020
TI  - Immediate adjuvant intravesical chemotherapy after transurethral resection of
      bladder tumor.

PMID- 17039021
TI  - Emerging strategies in the treatment of testis cancer.
AB  - The state of the art in the study and therapy of germ-cell tumors of the testis
      is reflected in this year's literature. For the majority of patients with germ
      cell tumors, the therapeutic dilemma no longer relates to cure. For such patients
      with low-volume non-seminomatous germ-cell tumors of the testicle and those with
      a pure seminoma, therapeutic dilemmas relate more to selection of the appropriate
      therapy to achieve cure, the toxicity of therapy, and the precise prediction of
      outcome. However, a high cure rate cannot be anticipated with equal frequency in
      those patients with high-volume non-seminomatous germ-cell tumors of the
      testicle.

PMID- 17039022
TI  - New chemotherapy regimens for metastatic bladder cancer.
AB  - M-VAC remains the standard of care for metastatic transitional cell carcinoma
      (TCC), but its limitations include significant toxicity and infrequent durable
      disease-free survival. Recent investigation has focused on the identification of
      novel chemotherapeutics with single-agent activity in metastatic TCC and on their
      incorporation into more active combination regimens. Paclitaxel, gemcitabine and
      ifosfamide are among the most active new agents. Numerous phase II trials of
      novel combinations have yielded promising preliminary results. Longer follow-up
      and results from randomized trials will be necessary to determine the impact of
      newer chemotherapy regimens on survival.

PMID- 17039023
TI  - Developments in bladder cancer monitoring.
AB  - The exclusive reliance on standard urinary cytology and cystoscopy for early
      diagnosis and monitoring of bladder cancer is now challenged by innovative
      techniques. A variety of urine tests employing immunostaining promise to enhance
      the value of cytological examination. Detection of tumor-associated antigens and
      substances present in the urine of patients harboring bladder cancer has reached
      a high degree of sophistication. Laboratory-based tests offer the possibility of
      early prediction of recurrence with a significant degree of accuracy. Equally
      exciting is the availability of rapid urine tests (point-of-care) that offer
      better sensitivity and specificity than cytology, deliver immediate results and
      provide an indication of the degree of tumor differentiation.

PMID- 17039024
TI  - Superficial transitional cell carcinoma: bacillus Calmette-Guerin (BCG) and other
      intravesical agents.
AB  - Adjuvant immuno- and/or chemotherapy intravesically has become a standard at
      least for patients with intermediate or high risk for recurrence. Whereas in the
      past cystectomy was a first-line therapy for patients with carcinoma in situ or
      high-grade T1 bladder tumor, radical surgery is today reserved for non-BCG
      responders or early recurrent disease.

PMID- 17039025
TI  - Muscle-invasive transitional cell carcinoma of the bladder: strategies for
      bladder preservation.
AB  - For patients with invasive bladder cancer, radical cystectomy remains the gold
      standard of treatment. However, based upon success with combination chemotherapy,
      physicians have begun to use this modality in an integrated approach with
      radiotherapy. This approach is of interest for elderly patients with poor medical
      conditions and for younger patients who may prefer to retain their bladders.
      Thorough transurethral resection of the bladder followed by chemotherapy with or
      without radiotherapy has become the focus of several studies. Bladder-conserving
      therapy may be offered to selected patients with invasive bladder cancer as a
      viable alternative to radical cystectomy.

PMID- 17039063
TI  - Current world literature.

PMID- 17039065
TI  - Neonatal hydronephrosis.
AB  - With fetal abnormalities diagnosed during maternal ultrasound becoming more
      commonplace, the management of neonatal hydronephrosis has become one of the most
      interesting and controversial subjects in pediatric urology. Although it is
      recognized that obstruction must be treated, it is also clear that hydronephrosis
      may well exist without significant obstruction. Numerous experimental and
      clinical studies of the urinary tract have failed to lead to a clear consensus.
      Our approach consists of careful observation of patients with moderate
      hydronephrosis in well functioning kidneys. In patients with reduced function or
      a renal pelvic diameter of greater than 3 cm and dilated calyces, we lean more
      towards surgical intervention. Overall, an individualized approach is necessary.

PMID- 17039066
TI  - Genital reconstruction.
AB  - Genital reconstruction is necessary in various types of congenital malformations.
      Although various surgical procedures may be used depending on the anomaly, the
      basic principles are the same. Three groups of pathology are discussed:
      hypospadias, ambiguous genitalia and exstrophy-epispadias complex. Progress
      continues to be made in modifying older techniques and creating new ones. Some
      investigators have focused on pain control and dressing materials. There is still
      much work to be done in this challenging area.

PMID- 17039067
TI  - Infections and vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR) is a common condition in children. It may cause and
      maintain urinary tract infections, eventually leading to progressive renal damage
      and end-stage renal disease. Ideally, VUR should be detected and treated before
      renal scarring occurs. Although fetal hydronephrosis on antenatal ultrasound may
      be the first indicator, the role of further diagnostic investigations in these
      newborns is still controversial. Because VUR is an inherited condition, offspring
      of women with a family history of VUR and urinary tract infection should be
      screened closely for early detection of VUR. Once diagnosed, however, the optimal
      management of VUR (i.e. medical or surgical treatment) remains controversial.
      Evidence-based treatment recommendations, like the American Urological
      Association guidelines, may aid physicians in their therapeutic decision making,
      but cannot replace personal experience or surgical skill.

PMID- 17039068
TI  - Enuresis, voiding dysfunction and neurogenic bladder in children.
AB  - This review covers bladder dysfunction in children. A significant amount of work
      has been done in the past year with regard to enuresis. The International
      Children Continence Society discussed the issues of bladder dysfunction,
      including enuresis, and this review covers the findings of that meeting. It also
      covers the articles that have been published on neurogenic bladder dysfunction as
      well as on posterior urethral valves.

PMID- 17039069
TI  - Renal diseases and transplantation in children.
AB  - The diseases that are most commonly responsible for renal damage and end-stage
      renal disease are unique in children. The devastating effect of chronic renal
      failure on the mental and physical development of children offers many
      challenging management problems. Although less than perfect, successful renal
      transplantation is considered the best available treatment option for children,
      with the alternative of dialysis often made difficult by access problems, growth
      retardation and renal osteodystrophy. Children comprise between 5 and 8% of our
      transplant programme, and we consider transplantation and dialysis to be
      complementary rather than competitive.

PMID- 17039070
TI  - Paediatric oncology.
AB  - Recent research into paediatric urologic oncology has identified a number of
      certain subgroups of neuroblastoma and Wilms' tumour, which allows a more
      tailored treatment of the individual child with respect to treatment sequelae and
      finance issues. The importance of surgery, radiotherapy and cytostatic treatment
      has to be individualized. The controversies regarding the management of
      rhabdomyosarcoma of the bladder and the prostate remain unresolved.

PMID- 17039072
TI  - Vasectomy reversal in the age of intracytoplasmic sperm injection.
AB  - The advent of intracytoplasmic sperm injection has revolutionized the treatment
      of male infertility and offers an alternative to vasectomy reversal as a
      treatment option for post-vasectomy infertility. Issues including morbidity, cost
      and therapeutic outcomes are, however, important considerations for both
      treatment options. Vasectomy reversal should be considered the ideal option for
      couples less than 15 years since vasectomy, couples interested in more than one
      child, couples without in-vitro fertilization insurance coverage and couples with
      no interest in assisted reproductive techniques. Intracytoplasmic sperm injection
      may be considered as the primary option for those couples with an older female
      partner especially if bilateral vasoepididymostomy may be required.

PMID- 17039073
TI  - Current concepts in the management of post-radical prostatectomy impotence.
AB  - Erectile dysfunction after radical retropubic prostatectomy has a multifactorial
      aetiology, including both neurogenic and vasculogenic factors. Postoperative
      potency is improved with preservation of the neurovascular bundles in a nerve
      sparing procedure. Preoperative and intraoperative identification and
      preservation of accessory pudendal arteries may also improve postoperative
      potency rates. The early institution of treatment with intracavernous alprostadil
      appears to improve postoperative potency rates. Treatment with newer therapeutic
      agents, such as Sildenafil and Invicorp, are both efficacious and well tolerated.

PMID- 17039074
TI  - Venous grafting for the correction of penile curvature in Peyronie's disease.
AB  - A number of procedures have been developed to correct penile deformity secondary
      to Peyronie's disease. In many cases, tunica-shortening procedures have had
      reasonable success. The most popular of these are tunical plication and Nesbit's
      wedge resection. However, these procedures shorten the penis and do not correct
      the hourglass deformity. Tunica-lengthening by using autologous or synthetic
      materials has been reported with varying success. However, notable shortcomings
      including graft contracture, recurrence, and impotence have been reported. This
      review describes our experience with tunica incision and venous grafting.

PMID- 17039075
TI  - Fertility considerations in the patient with testis cancer.
AB  - Fertility is an important aspect in the quality of life of patients surviving
      testis cancer. The question of future fertility should be considered before
      treatment commences, and the patient's wishes may require modification of
      therapeutic regimens. The biggest improvement in the management of male
      infertility over the past 10 years has been the introduction of intracytoplasmic
      sperm injection (ICSI). This review gives a perspective of these issues, together
      with an outline of recent papers on the subject.

PMID- 17039076
TI  - Viagra: what's all the fuss about?

PMID- 17039077
TI  - Current world literature.

PMID- 17039079
TI  - SLE in a United States-Mexico border community.
AB  - This report describes the results of a clinic-based study conducted to verify a
      community-reported excess prevalence of systemic lupus erythematosus (SLE) and a
      possible connection between ethnicity and environmental factors in the reporting
      of SLE in the United States-Mexico border town of Nogales, Arizona. A community
      group in Nogales reported 37 cases of SLE in its community, suggesting a
      prevalence rate of 200 per 100,000. This report describes 19 definite and 7
      probable cases of SLE using the 1982 American College of Rheumatology criteria.
      All definite and probable cases were self-identified, Mexican-American females.
      This yields a prevalence rate of 94 per 100,000, among the highest reported to
      date. The majority of cases resided within 3 miles of the United States-Mexico
      border and within 1 mile of the polluted Nogales Wash or ground wells with
      documented toxins. It remains to be determined whether this confirms that SLE is
      more common in Mexican-Americans or whether environmental factors, especially
      pollutants, are predominantly responsible. In addition to the need to be aware
      about the apparent increased risk of SLE in many Latin-Americans, clinicians
      should ask about possible environmental factors.

PMID- 17039080
TI  - Serum and urine nitrite and citrulline levels among patients with systemic lupus
      erythematosus: a possible addition to activity parameters?
AB  - Nitric oxide (NO) plays a significant role in the inflammatory process and has
      been implicated in several autoimmune disorders. This study was carried out
      prospectively to estimate the levels of nitrite and citrulline in the serum and
      urine, as surrogate markers of NO production, among patients with systemic lupus
      erythematosus (SLE). Forty-seven patients and 44 age- and sex-matched, healthy
      volunteers were studied. Nitrite and citrulline were measured in serum and urine
      by spectrophotometry.Median serum nitrite and citrulline levels and urine
      citrulline levels were higher among patients as compared with controls (p <
      0.05). Patients with skin involvement stood out and had higher median serum and
      urine citrulline levels (p < 0.05). Disease activity correlated with steroid
      dosage, serum nitrite levels, and serum and urine citrulline levels (p < 0.05).
      Steroid dosage correlated with serum citrulline level (p < 0.05). Serum and urine
      citrulline levels correlated with each other (p < 0.01). In the subset of 13
      individuals with renal involvement, serum and urine citrulline levels correlated
      with each other (p < 0.01) as did urine nitrite and citrulline levels (p <
      0.05).NO production is increased among patients with SLE, and this increase
      correlates with disease activity and dosage of steroids used. The addition of a
      urine test to measure NO production as a marker of disease activity using simple
      spectrophotometry can be a valuable adjunct to other tests, can obviate the need
      for drawing a blood sample for this purpose, and can be repeated as often as
      necessary.

PMID- 17039083
TI  - Early onset methotrexate-induced pancytopenia and response to G-CSF: a report of
      two cases.
AB  - Methotrexate (MTX) is one of the most widely used antirheumatic drugs for the
      treatment of rheumatoid arthritis. Whereas the hepatotoxicity of methotrexate is
      well recognized, the hematologic toxicity, namely, pancytopenia, is still a
      concern and is potentially fatal. We report two cases of early-onset methotrexate
      induced pancytopenia that were successfully treated with granulocyte colony
      stimulating factor (G-CSF). The pancytopenia improved with 3 days of
      administration. A review of the literature revealed at least 146 reported cases
      of MTX-induced pancytopenia. Significant risk factors for myelotoxicity included
      renal impairment, infection, and hypoalbuminemia. Successful management includes
      prompt discontinuation of MTX, intravenous folinic acid, high-dose steroids and,
      as in our case, G-CSF.

PMID- 17039084
TI  - Pneumococcal pyomyositis: a patient with diagnostic problems and complications.
AB  - Pyomyositis is an uncommon condition that may present a difficult problem in
      diagnosis. We report the development of Streptococcus pneumoniae pyomyositis
      involving the iliacus, iliopsoas, and gluteus muscles in a patient with elevated
      serum levels of antinuclear and antiphospholipid antibodies but without clinical
      evidence of connective tissue disease. Magnetic resonance imaging demonstrated
      rapid evolution of the infection, with progression from muscle edema to abscess
      formation over a period of 10 days. The diagnosis was initially missed, and
      osteomyelitis and sacroiliitis developed. Pyomyositis should be suspected in
      patients with the acute onset of severe, localized muscle pain and fever. As in
      this case, failure to promptly diagnose and treat this infection can result in
      significant morbidity.

PMID- 17039085
TI  - Recurrent alveolar hemorrhage and pulmonary capillaritis in the "primary"
      antiphospholipid syndrome.
AB  - Pulmonary involvement in the primary antiphospholipid syndrome (PAPS) has
      generally been on the basis of thromboembolism. We describe a patient with
      hemorrhagic alveolitis, a life-threatening complication that must also be
      considered. The patient was a 63-year-old Caucasian man who had a past history of
      recurrent deep vein thromboses as well as an arterial occlusion of the left
      popliteal artery and who developed hemorrhagic alveolitis and capillaritis at age
      57 years, which was treated with long-term cyclophosphamide, steroids, and
      anticoagulation. Four years later, he had a recurrence of the same condition, and
      a positive lupus anticoagulant test was found. Severe thrombocytopenia, diagnosed
      as idiopathic thrombocytopenic purpura, was treated with platelet transfusions
      and increasing steroid dosage. Hemorrhagic adrenal infarction supervened at this
      time, and a septicemic illness was treated with intravenous antibiotics. Diffuse
      alveolar pulmonary hemorrhage is an unusual complication of the APS that is being
      increasingly reported, and recognition of its possible fatal course is of great
      importance for the treating physician. Severe thrombocytopenia that could
      contribute to hemorrhage may also accompany the APS, but this is unusual.

PMID- 17039086
TI  - Is Listeria monocytogenes an important pathogen for prosthetic joints?
AB  - Listeria monocytogenes usually causes meningitis or bacteremia, often in
      immunocompromised adults, pregnant women, or infants. We report a case of septic
      arthritis caused by L. monocytogenes in a patient with seronegative rheumatoid
      arthritis (RA) whose hip replacement was infected. She subsequently died,
      probably secondary to an adult respiratory distress syndrome, a rare complication
      of listerial infection. We also reviewed all 18 previously reported cases of
      septic arthritis caused by L. monocytogenes. The frequency of underlying RA,
      diabetes, neoplastic disease, and immunosuppressive therapy is prominent, as is
      the concurrent presence of a previous knee or hip replacement. Thus, the
      simultaneous presence of immune suppression and certain medical disorders or
      their treatment and a prosthetic joint should alert the clinician to the
      possibility that L. monocytogenes is the offending microbial agent. In contrast,
      in immunocompetent persons the usual Gram-positive cocci such as staphylococci,
      streptococci, or even pneumococci predominate. Although the outcome of
      appropriate treatment with penicillin or ampicillin alone (or with an
      aminoglycoside or trimethoprim/sulfamethoxazole in penicillin-allergic
      individuals) is usually favorable, complicating medical disorders can lead to
      death. Cephalosporins are rarely effective antimicrobial agents in patients with
      listeriosis.

PMID- 17039087
TI  - Postpartum multifocal avascular necrosis: what are the possible etiologies?
AB  - Avascular necrosis of bone (osteonecrosis) that is atraumatic is most frequently
      associated with corticosteroid excess or alcoholism and usually involves the
      femoral head. We report a case of multifocal avascular necrosis in a 38-year-old
      woman with autoimmune Addison's disease taking corticosteroid replacement
      therapy. The onset of joint symptoms occurred 6 months after a pregnancy
      complicated by acute fatty liver and disseminated intravascular coagulation.
      Although both knees and ankles were involved, an unusual feature is that the hips
      were spared. As illustrated in this patient, avascular necrosis is frequently
      misdiagnosed in cases of joint pain of acute onset and may occur in the context
      of physiologic replacement doses of corticosteroids. Etiologic factors can
      precede the onset of symptoms and the diagnosis by several months.

PMID- 17039088
TI  - Worsening of arthritis with antiretroviral therapy: the coexistence of rheumatoid
      arthritis and human immunodeficiency virus infection revisited.
AB  - The observation of remission occurring in several rheumatoid arthritis (RA)
      patients who subsequently became infected with human immunodeficiency virus (HIV)
      suggested that these diseases are mutually exclusive. Subsequent case reports of
      progression of destructive rheumatoid arthritis, even with depleted CD4 cell
      counts, seemed to imply that active RA may be independent of CD4 lymphocyte
      number and function. We report an HIV-infected individual who developed
      rheumatoid arthritis, which rapidly worsened with the initiation of
      antiretroviral therapy. The worsening disease course correlated with the increase
      in CD4 cell count and with the decrease in HIV viral load, perhaps suggesting a
      central role for the CD4 cells in the pathogenesis of rheumatoid arthritis in
      this particular patient. Among the therapeutic options to consider in such a
      patient, indomethacin and hydroxychloroquine may offer additional benefit of
      inhibiting viral replication. The cautious use of methotrexate with several
      limitations is possible, although sulfasalazine (to which our patient responded)
      may be a safer option.

PMID- 17039089
TI  - Malignancies and autoimmune rheumatic diseases.

PMID- 17039090
TI  - Improved lung function in patients with scleroderma and interstitial disease with
      the use of cyclophosphamide.

PMID- 17039091
TI  - Practice tip 15. Prevention of inframammary moniliasis.

PMID- 17039092
TI  - Atypical Behcet's disease with peripheral erosive arthopathy.

PMID- 17039093
TI  - Serum leptin levels in patients with rheumatoid arthritis.

PMID- 17039094
TI  - Mondor's disease and polymyalgia rheumatica: a case report.

PMID- 17039095
TI  - Finessing fibromyalgia.

PMID- 17039097
TI  - Crohn's disease arthritis treated with infliximab: an open trial in four
      patients.
AB  - Four patients with Crohn's disease arthritis, who were unresponsive to
      conventional treatment, improved very rapidly and safely with the use of
      infliximab, the chimeric antibody directed against tumor necrosis factor alpha.
      The patients were able to stop or significantly decrease other antirheumatic
      medications after the infliximab infusions. It is likely that tumor necrosis
      factor plays a major role in the arthritis as well as the bowel involvement that
      is seen in Crohn's disease. Suppression of this cytokine may effectively
      ameliorate Crohn's disease arthritis in some patients.

PMID- 17039098
TI  - The treatment of fibromyalgia with cranial electrotherapy stimulation.
AB  - In cranial electrotherapy stimulation (CES), micro-current levels of electrical
      stimulation are passed across the head via electrodes clipped to the ear lobes.
      After successful clinical use of CES with fibromyalgia patients in our clinic, it
      was decided to test these results with a double-blind, placebo-controlled study
      in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES
      treatments, sham CES treatments, or were held as wait-in-line controls for any
      placebo effect in the sham-treated patients. Treated patients showed a 28%
      improvement in tender point scores, and a 27% improvement in self-rated scores of
      general pain level. The number of subjects rating their quality of sleep as poor
      dropped from 60% at the beginning of the study to 5%. In addition, there were
      significant gains in the self-rated feelings of well-being and quality of life,
      plus gains in six stress-related psychological test measures. No placebo effect
      was found among the sham-treated controls. A theoretical role of CES in affecting
      the brain's pain message mechanisms and/or neurohormonal control systems is
      discussed. It is concluded that CES is as effective as the drug therapies in
      several trials, with no negative side effects, and deserves further consideration
      as an additional agent for the treatment of fibromyalgia.

PMID- 17039100
TI  - Dissection of the temporal artery in a patient with giant cell arteritis.
AB  - A 74-year-old woman presented to her rheumatologist with classic symptoms of
      giant cell arteritis. The temporal arteries were strikingly swollen, warm, and
      erythematous. On biopsy of the right temporal artery, a focal dissection was
      found associated with a pan-arteritis and giant cells. Isolated temporal artery
      dissection in giant cell arteritis has not been reported previously. We propose
      that the unusually intense vascular inflammation may have weakened the vessel
      wall, so that the dissection occurred during the routine physical exam or biopsy.
      We believe this case illustrates that physicians should take special care in the
      examination of floridly inflamed vessels, because vigorous palpation might lead
      to dissection. In the case of patients with giant cell arteritis, dissection may
      result in an increased risk of ischemic complications, such as scalp necrosis.

PMID- 17039101
TI  - Salmonella group D septic arthritis and necrotizing fasciitis in a patient with
      rheumatoid arthritis and diabetes mellitus.
AB  - Necrotizing fasciitis is an uncommon manifestation of Salmonella infection. We
      report a case of Salmonella group D septic arthritis complicated with necrotizing
      fasciitis in a 51-year-old man who had noninsulin dependent diabetes mellitus and
      rheumatoid arthritis. He presented with fever and severe right hip pain
      complicated with septic shock and disseminated intravascular coagulation.
      Crepitation was noticed upon physical examination, and plain films showed
      numerous air bubbles in the soft tissue around the hip joint. Prompt antibiotic
      therapy and surgical management were performed with a successful response. The
      causative organism was Salmonella group D. Antibiotic was given in the total
      course of 3 months, and there was no relapse of salmonellosis after 2 years
      follow up. The differential diagnosis of causes of non-clostridial crepitant soft
      tissue and muscle infections must include Salmonella, especially in patients who
      have underlying diseases or are taking immunosuppressive drugs. Prompt management
      is needed to reduce mortality and morbidity. Long-term suppressive therapy may be
      needed to prevent relapse.

PMID- 17039102
TI  - Spontaneous abdominal hemorrhage with AA-amyloidosis and vasculitis in a patient
      with rheumatoid arthritis.
AB  - Both rheumatoid vasculitis and amyloidosis in rheumatoid arthritis (RA) are
      uncommon. We describe a patient in whom they occurred together and were
      associated with fatal intra-abdominal hemorrhage. A 56-year-old Caucasian woman
      was referred because of increasing lethargy, edema, and proteinuria. She had
      suffered from seropositive, erosive, nodular RA for 14 years. Previously, she had
      undergone numerous joint replacements, a thyroidectomy for amyloid-associated
      (AA) amyloidosis of the thyroid that caused a large goiter and a renal biopsy
      that showed renal AA-amyloidosis in the context of nephrotic syndrome. As her
      condition deteriorated, this patient became increasingly reluctant to go to the
      hospital and to take drugs beyond analgesics. Thus, her RA was chronically under
      treated. While in the hospital for evaluation, this patient suddenly developed
      hypotension, tachycardia, and a severe colicky left-sided abdominal pain
      radiating from the left upper quadrant/epigastric region to the left iliac fossa.
      Computed tomography (CT) showed a large amount of echogenic free fluid within the
      abdomen and marked thickening of the omentum. At laparotomy, 2 liters of free
      blood was found adjacent to a hematoma of the greater omentum, and it was
      evacuated without identification of a discrete bleeding point. All solid and
      hollow organs were normal. The omentum was noted to be very friable. She
      developed a more disseminated bleeding diathesis and persistent peritoneal
      hemorrhage via her abdominal drains. She succumbed shortly afterward. Histology
      revealed extensive omental hemorrhage and one large vessel within the area of
      hemorrhage showed a severe necrotizing vasculitis. Extensive amyloid deposition
      was also found within the walls of the smaller omental arterioles. Vasculitis in
      the context of RA is relatively rare and is associated with under treated,
      seropositive disease. Skin and nerve involvement are most common, but bowel
      involvement has been reported, with a highly significant morbidity (partly due to
      late presentation/recognition). Similarly, AA-amyloidosis is a rare but feared
      long-term concomitant of under treated RA. Early recognition can permit
      successful anti-inflammatory therapy to affect a clinical and pathological
      remission; continued inflammatory stimulation is associated with rapid
      progression and demise. Chronically under treated patients with RA are more prone
      to rare but potentially devastating complications. Gastrointestinal catastrophes
      are a feature of both rheumatoid vasculitis and of amyloidosis, here uniquely co
      localized.

PMID- 17039103
TI  - Wegener's granulomatosis presenting as subglottic stenosis.
AB  - Wegener's granulomatosis is an uncommon disease process that causes necrotizing
      vasculitis predominantly in the lungs, kidneys, and upper air-ways. Subglottic
      stenosis has been observed in up to 20% of patients with established diagnosis of
      Wegener's granulomatosis, but it is rarely the initial manifestation of the
      disease. This case report presents a patient with Wegener's granulomatosis who
      had subglottic stenosis as predominant initial manifestation, without signs of
      lung or kidney involvement. The diagnosis was unclear initially due to the
      absence of damage to these organs and to the nonspecificity of the initial biopsy
      findings. After stabilizing the patient, an elevated cytoplasmic pattern of
      antineutrophil cytoplasmic antibodies titer was obtained, which played an
      important role in the diagnostic process and led to a second biopsy that showed
      vasculitis. The patient had an excellent response to prednisone, methotrexate,
      and trimethoprim/sulfamethoxazole, but as with many such cases, she also required
      tracheo-laryngoplasty.

PMID- 17039104
TI  - Cardiac tamponade: a life-threatening complication of Still's disease.
AB  - Pericarditis, a common feature of adult-onset and juvenile-onset Still's disease,
      is rarely complicated by cardiac tamponade. We report one patient with juvenile
      onset and another with adult-onset Still's disease presenting with pericardial
      tamponade. On the basis of our experience and analysis of literature, we suggest
      early identification of pericarditis and the life-threatening complication of
      tamponade, with institution of aggressive intervention with corticosteroids and,
      if necessary, pericardiocentesis and pericardial window formation. These cases
      remind physicians about the need to include Still's disease in the differential
      diagnosis of pericarditis and tamponade and to not neglect the potential of
      severe systemic inflammation to lead to fatal complications in this group of
      patients.

PMID- 17039105
TI  - Ticlopidine-induced lupus.
AB  - Ticlopidine is a widely used drug for prevention of stroke and other serious
      vascular events with a multitude of possible side effects. An increasing number
      of drugs are being recognized as the triggering agents of drug-induced lupus. We
      describe three patients in whom the etiologic connection between ticlopidine and
      lupus was supported by the appearance of lupus-like features (fever, rash,
      arthritis, renal involvement, positive antinuclear and antihistone antibodies),
      shortly after drug initiation, and their gradual resolution after its
      discontinuation. If suggested by clinical or/and laboratory findings (fever of
      unknown cause, musculoskeletal involvement, hematologic abnormalities), the
      possibility of ticlopidine-induced lupus should be taken into consideration and
      appropriate investigations should be performed. Patients should resolve slowly
      but completely after withdrawal of ticlopidine.

PMID- 17039106
TI  - Thrombotic thrombocytopenia purpura in a patient with systemic sclerosis.
AB  - Thrombotic thrombocytopenic purpura (TTP) has been associated with scleroderma
      renal crises (SRC) in the past. However such reports markedly diminished after
      the onset of ACE inhibitor use. Recently, reports again have surfaced that
      describe scleroderma patients presenting with clinical evidence of TTP. We
      describe a 50-year-old female with longstanding limited cutaneous scleroderma who
      presented with hematochezia and thrombocytopenia along with other findings
      suggesting TTP. A colon biopsy revealed thrombi within the lumen. Her course was
      complicated by renal failure and hypertension that did not respond to ACE
      inhibitor therapy alone. She improved after a course of plasma exchange. She was
      discharged home only to return 2 months later with grand mal seizures and
      hypertension. During her course she developed adult respiratory distress
      syndrome. She again responded to plasma exchange and she was discharged home. She
      has remained stable for 2 years. This report emphasizes the importance of fully
      evaluating patients with longstanding limited cutaneous scleroderma who present
      with renal failure, hypertension, and thrombocytopenia in association with
      multiorgan complications. All possible etiologies, including SRC, TTP,
      vasculitis, and sepsis should be considered. Tissue biopsies (in this case, a
      colon biopsy revealed thrombi within the vessel lumen) may prove beneficial in
      assisting with the diagnosis. For such patients who fail treatment with ACE
      inhibitors, plasma exchange may be considered.

PMID- 17039107
TI  - Hip pain as the presenting manifestation of acute gouty sacroiliitis.
AB  - Gout can present in a variety of less typical forms. We describe a case of an
      elderly woman presenting with hip and lower extremity pain. It remained
      undiagnosed for several days but proved to be secondary to gouty involvement of
      the right sacroiliac (SI) joint. Monosodium urate crystals were identified in
      computed tomographic guided aspiration of the SI joint. The importance of
      obtaining a good history and performing a complete physical examination if the
      diagnosis of sacroiliitis (or any other musculoskeletal disorder) is to be made,
      its cause defined, and proper treatment instituted is emphasized.

PMID- 17039109
TI  - Treatment of rheumatic disease by tumor necrosis factor-alpha blockade: knowns
      and unknowns.

PMID- 17039108
TI  - Alveolar hemorrhage and pulmonary hypertension in systemic sclerosis: a continuum
      of scleroderma renal crisis?
AB  - Alveolar hemorrhage occurs as a complication of systemic inflammatory diseases.
      In addition to alveolar hemorrhage, patients with systemic sclerosis (SSc) may
      suffer from digital infarction, pulmonary hypertension, and renal crisis.
      Although a common pathogenesis of this disease that explains the variety of
      problems during a patient's illness has yet to be identified, the unique
      characteristics of SSc may alter our approach to alveolar hemorrhage in this
      patient population. We describe a patient with SSc, who presented with pulmonary
      hypertension and alveolar hemorrhage complicated by features suggesting re
      occurrence of scleroderma renal crisis. Our successful management of this
      patient, with complications that are usually of high morbidity, may be attributed
      to our judicious use of glucocorticosteroid therapy and maximization of
      angiotensin-converting enzyme inhibition. In view of the potential for
      glucocorticoids to precipitate scleroderma renal crisis, we suggest caution in
      the use of these medications for manifestations that may be similar in their
      pathogenesis.

PMID- 17039110
TI  - Dermatology vignette. Pseudoporphyria caused by NSAIDs.

PMID- 17039111
TI  - Practice tips. Treatment of chronic thoracic pain with interscapular weights.

PMID- 17039112
TI  - Comments regarding Hans Reiter's role in Nazi Germany.

PMID- 17039114
TI  - Can drug-induced lupus cause aortic aneurysm?

PMID- 17039115
TI  - A case of mixed connective tissue disease with cystic pancreatitis: successful
      treatment by cyclophosphamide.

PMID- 17039116
TI  - Celecoxib and rofecoxib: a distinction with a difference?

PMID- 17039117
TI  - Spin doctors.

PMID- 17039119
TI  - Systemic lupus erythematosus in men: a retrospective analysis in a Veterans
      Administration Healthcare System population.
AB  - Systemic lupus erythematosus (SLE), a connective tissue disease of unknown
      etiology, is generally considered to occur in women of child-bearing age and to
      be uncommon among men . Because of the female predominance in most studies, less
      is known about the disease in men. To begin to better understand lupus in men, we
      retrospectively analyzed all the SLE patients from all the hospitals in the
      Department of Veterans Affairs (VA) system, a population that is predominantly
      male. Between 1987 and 1996, 2614 SLE patients were retrieved from the VA
      databank; 2144 were male, making this the largest group of male patients with SLE
      reported in United States of America. Age, racial and geographic distribution,
      comorbidities, and mortality of the SLE patients are reported. This study
      suggests that SLE men in this population are older at onset of disease, have
      different comorbidities, and have a higher mortality at 1 year than women with
      SLE. These findings suggest that men with SLE have a more complex clinical course
      than women, although the data do not illuminate whether the comorbidities are due
      to or coincident with SLE. On the basis of these data, practitioners are reminded
      to consider SLE in the differential diagnosis for older men and be attentive to
      the frequent presence of comorbidities such as cardiac ischemia and neoplasms.
      Because of the identified regional variations in demographics, comorbidities, and
      mortality, this study suggests the need for future SLE studies to include data
      from multiple geographic areas.

PMID- 17039120
TI  - COX-2 specific inhibitors in the management of osteoarthritis of the knee: a
      placebo-controlled, randomized, double-blind study.
AB  - COX-2 specific inhibitors have demonstrated significant safety advantages and
      comparable efficacy in osteoarthritis (OA) compared with conventional
      nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials
      between COX-2 specific inhibitors have been published. In this double-blind,
      placebo-controlled, parallel group, multicenter study, 182 patients (> or =40
      years old) with OA of the knee were randomly assigned to treatment with celecoxib
      200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6
      weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at
      early termination. At Week 6, celecoxib and rofecoxib treatment resulted in
      similar mean changes from baseline (p > 0.55) in arthritis pain visual analogue
      scale, patient's global assessment, and total score for WOMAC; all changes were
      superior to placebo (p < 0.05). In the patient's global assessment of arthritis
      pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients
      improved by > or =1 grade, compared with 50% of placebo patients (celecoxib, p =
      0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the
      active comparators; however, celecoxib-treated patients had significantly fewer
      adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which
      suggests that celecoxib may have a better gastrointestinal tolerability profile
      than rofecoxib at these doses. Adverse events that prompted withdrawal occurred
      in fewer than 7% of patients, and the overall incidences were similar between the
      active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer
      comparable efficacy and are an effective alternative to conventional NSAIDs in
      the management of OA.

PMID- 17039121
TI  - The long-term use of azathioprine in patients with psoriatic arthritis.
AB  - Despite the widespread use of methotrexate in the treatment of psoriatic
      arthritis (PsA), there are patients who are either refractory, develop toxicity
      to, or refuse to take methotrexate. In search of an alternative, we studied long
      term tolerability of and clinical response to azathioprine (AZA) in PsA patients
      in comparison with matched controls and followed them in a longitudinal clinic.
      Twenty-eight of 485 patients followed prospectively between 1978 and 1998 took
      AZA during their clinic follow-ups. Eighteen of the 28 took AZA for 12 months and
      were included in the study. AZA was well tolerated by most patients, even in the
      long-term. Although there was no statistically significant difference in the
      reduction in number of actively inflamed joints between AZA-treated patients and
      controls, and AZA was no better in preventing progression of damage, AZA was
      still as good as the other medications. Consequently, AZA was often given to
      individuals who had not responded to other medications in the past. We provide
      illustrative case reports in which AZA also controlled psoriasis, and we conclude
      that, whereas AZA is not superior to other medications in the treatment of PsA,
      it may be safely used and it provides an alternative therapy for patients with
      PsA.

PMID- 17039122
TI  - Exocrine dysfunction of the pancreas in patients with chronic polyarthritis.
AB  - We studied the extent to which exocrine dysfunction of the pancreas is seen among
      patients with severe chronic polyarthritis and whether it might account for some
      gastrointestinal symptoms. Our series consisted of 50 such chronic polyarthritis
      cases; most had rheumatoid arthritis but had neither diagnosed or suspected
      pancreatitis nor primary Sjogren's syndrome. They were asked about
      gastrointestinal (GI) and sicca symptoms. The exocrine function of each pancreas
      was evaluated by the fecal elastase-1-enzyme test. Thirty-two patients had GI
      symptoms at least weekly. Forty had sicca eye syndrome and 26 had dry mouth.
      There were two cases (4%; 95% confidence interval, 1-14%) with abnormally low
      fecal elastase-1-enzyme test level. Chronic GI and sicca symptoms are frequent
      among patients with severe chronic polyarthritis. Secondary Sjogren's syndrome
      may cause exocrine insufficiency in the pancreas. That circumstance was not
      common here, but it is worth remembering because it can be diagnosed by a
      noninvasive method, and enzyme preparation treatment is available for the
      symptoms, especially for postprandial pain and distention of the stomach.

PMID- 17039123
TI  - Propylthiouracil-induced microscopic polyangiitis.
AB  - The use of propylthiouracil (PTU) has been associated with various forms of
      vasculitis. We herein describe the case of a patient with Grave's disease who,
      after years of PTU therapy, developed a necrotizing vasculitis with anti-serine
      protease-3 antibodies. Despite treatment with corticosteroids and
      cyclophosphamide, the patient died of intra-alveolar hemorrhage secondary to her
      vasculitis. Based on the vessel size involved, the organ distribution of
      pathologic findings, and lack of granulomas, autopsy findings were felt to be
      more consistent with microscopic polyangiitis (MPA) than with her original
      clinical diagnosis of Wegener's granulomatosis. Her case satisfied both clinical
      and pathologic criteria for MPA. An MPA diagnosis is important to consider in
      similar clinical presentations because therapy may just need to be early
      withdrawal of an inciting drug, such as PTU, and the initiation of
      corticosteroids without cytotoxic therapy.

PMID- 17039124
TI  - Corticosteroid-sparing effect of etanercept in idiopathic panuveitis resistant to
      immunosuppressive therapy.
AB  - Uveitis, an inflammatory eye disease with varying immunopathogenic mechanisms,
      may be associated with autoimmune disorders, may be secondary to infection, or
      may be idiopathic. Response to treatment of uveitis is inconsistent. In this
      report we describe an adult with idiopathic panuveitis who attempted to lower his
      oral corticosteroid dose from intolerable levels but was unable to do so because
      of the reappearance of symptoms. His 8-year course was managed with ocular and
      systemic corticosteroids, methotrexate, and cyclosporine, which allowed only
      partially successful control of his ocular inflammation. Complete control was not
      achieved until the addition of etanercept. With this case report we are the first
      to describe the complete response of idiopathic panuveitis to etanercept. Our
      success with this patient strongly supports the critical role of tumor necrosis
      factor in the immunopathogenesis of some cases of idiopathic panuveitis.
      Furthermore, etanercept offers a relatively nontoxic, safe option in cases of
      panuveitis that are unresponsive to traditional immunosuppressive therapy.

PMID- 17039125
TI  - HELLP-like syndrome associated with hepatic necrosis in a patient with systemic
      lupus erythematosus.
AB  - Hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome is often
      associated with preeclampsia or hypertension in pregnancy. Pregnancy in patients
      with systemic lupus erythematosus (SLE) may be complicated by development of a
      lupus flare with thrombocytopenia, hypertension and renal insufficiency, which
      may be difficult to distinguish from preeclampsia. We describe a 20-year-old
      patient with SLE and anticardiolipin antibodies who developed a HELLP-like
      syndrome during 2 successive pregnancies without the more typical symptoms of
      preeclampsia or hypertension. This unusual presentation of HELLP syndrome during
      pregnancy in a patient with SLE was evidenced by hematologic and liver enzyme
      abnormalities as a sign of ongoing hepatic necrosis. Early recognition of this
      syndrome is important because it may result in rapid deterioration with
      progressive hepatic necrosis that can be reversible with early termination of
      pregnancy.

PMID- 17039126
TI  - Questioning the sensitivity of magnetic resonance imaging in early septic
      spondylodiscitis.
AB  - Septic spondylodiscitis is an uncommon disease, but one with serious
      complications and potentially high morbidity and mortality. The diagnosis is
      sometimes delayed, particularly in those patients with an insidious mode of onset
      and nonspecific symptoms. Several imaging methods are available to facilitate the
      early diagnosis of septic spondylodiscitis, and of these methods magnetic
      resonance imaging (MRI) has been reported to be the most sensitive, revealing
      abnormalities earlier than plain x-ray, gallium scan and bone scan. We report a
      case of septic spondylodiscitis in which MRI did not demonstrate evidence of
      discitis after a symptom period of seven days. The diagnosis was later confirmed
      by bone scan and repeat MRI. We suggest that a negative or equivocal MRI cannot
      exclude infective spondylodiscitis, especially in the early stages of the disease
      process. In such cases, it is important to note that the addition of a short tau
      inversion recovery sequence will increase the sensitivity of MRI, and,
      additionally, gadolinium should be administered if the magnetic resonance study
      is negative and a strong clinical suspicion of spondylodiscitis exists.

PMID- 17039127
TI  - Successful pamidronate treatment of severe and refractory regional migratory
      osteoporosis.
AB  - We report the case of a middle-aged patient with repeated attacks of regional
      migratory osteoporosis of the lower limbs, manifesting as severe pain and
      swelling of both joint and periarticular areas, and marked physical disability
      during a period of 2 1/2 years. After the therapeutic failure of conservative
      therapy (physical therapy, rehabilitation therapy, analgesics and nonsteroidal
      anti-inflammatory drugs (NSAIDs)) and after the correct diagnosis was reached,
      pamidronate treatment was instituted. The results were a rapid, complete, and
      long-lasting remission of the symptoms and the renewal of the patient's previous
      activities. Intravenous biphosphates are proposed as a safe and promising therapy
      for regional migratory osteoporosis. To our knowledge, this is the first report
      of pamidronate treatment for this condition.

PMID- 17039128
TI  - Amyopathic dermatomyositis in children: a diagnostic and therapeutic dilemma.
AB  - Juvenile dermatomyositis is an inflammatory disease of unknown etiology that
      primarily affects skin and muscles. The pathognomonic Gottron's sign consists of
      symmetric macules and papules on the dorsal aspect of the interphalangeal joints
      and exterior areas of the big joints. A periorbital violaceous (heliotrope) skin
      rash is also characteristic. There may be a discordance in time of presentation
      of the skin and muscle disease, and a small subset of patients apparently do not
      develop muscle disease at all. The absence of muscle involvement is termed
      'amyopathic dermatomyositis.'We describe two children who presented with the
      characteristic rash of juvenile dermatomyositis but with no clinical evidence of
      muscle involvement. One developed muscle weakness 3 years later. Neither patient
      had a full muscle work-up at the onset of the disease, which left questions about
      diagnoses and whether or not there may have been subtle muscle involvement. On
      the basis of our literature review, the outcome of these patients is uncertain,
      although it appears that myositis develops in many, maybe most, affected
      children. We suggest that in the absence of muscle disease, application of
      sunscreen and administration of hydroxychloroquine sulfate may ameliorate the
      rash. More aggressive treatment will need to be given when muscle involvement can
      be demonstrated.

PMID- 17039129
TI  - Kawasaki syndrome in an adult: case report and review of the literature in
      adolescents and adults.
AB  - Kawasaki syndrome in adults is very rare, with fewer than 50 cases reported in
      the English-language literature. We describe the case of a physician with
      Kawasaki syndrome and summarize the clinical features and treatment of 11
      patients in the literature since the last review in 1994. Our patient presented
      with high fever, conjunctivitis, and arthralgias, then developed progressive
      toxicity with oral lesions, cervical adenopathy, and desquamation of the fingers
      and toes. No exanthematous rash or coronary artery aneurysms were found. Recovery
      was rapid after therapy with aspirin and intravenous immunoglobulin (IVIg). The
      diagnosis of Kawasaki syndrome depends on clinical criteria and the exclusion of
      other diseases. This diagnosis can be challenging to make in an adult,
      particularly when it presents without all typical features. Kawasaki syndrome
      must be considered nonetheless in an adult with unexplained fever of more than 5
      days duration, because early diagnosis and combination therapy with aspirin and
      IVIg can prevent the life-threatening complication of coronary artery aneurysms.

PMID- 17039132
TI  - Baker cyst calcifications in a patient with rheumatoid arthritis.

PMID- 17039130
TI  - Periostalgia pubis: a cause of chronic abdominal pain.
AB  - Periostitis pubis has been proposed as a new clinical entity, one characterized
      by abdominal pain and tenderness over the os pubis. Periostitis pubis, as defined
      by Rubenstein , is inflammation at the insertion point of the anterior abdominal
      musculature onto the periosteum of the os pubis. A case is described in which the
      patient underwent multiple invasive diagnostic procedures before seeking help at
      the author's medical facility with a clinical problem similar to periostitis
      pubis. Her pain was completely relieved by infiltration of the tender superior
      surface of the os pubis. It is suggested that a more appropriate term for this
      problem may be 'periostalgia pubis. As no evidence exists that inflammation is
      involved in the pathophysiology, the primary goal of this case description is to
      promote recognition of the disorder which is probably under reported. It is hoped
      that recognition will lead to further information regarding the natural history
      and prevalence of the disorder.

PMID- 17039133
TI  - Practice tips. 17. Minimizing falls while bathing.

PMID- 17039134
TI  - Thoughts on Japanese versus North American rheumatology.

PMID- 17039135
TI  - Of skin and bones.

PMID- 17039137
TI  - Metal sensitivity in patients with orthopedic implants.

PMID- 17039136
TI  - Psoriatic arthritis, methotrexate, and liver toxicity.

PMID- 17039138
TI  - Weight loss and exercise walking reduce pain and improve physical functioning in
      overweight postmenopausal women with knee osteoarthritis.
AB  - We conducted an uncontrolled pilot study to determine the effects of a weight
      loss and walking program on knee pain and physical function in overweight and
      obese (body mass index; BMI [kg/m] 25-29.9 and BMI > or = 30, respectively)
      postmenopausal women with knee osteoarthritis (OA). Forty-eight such women
      completed self-report (Western Ontario and McMaster University Osteoarthritis
      Index (WOMAC)) and performance-based measures of physical function ("up and go"
      test, 6-min walk) and enrolled in a 6-month intervention that included weekly
      nutrition classes and an exercise-walking program. The intervention produced an
      average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program.
      There also were significant improvements in the 6-min walk and on VO(2max).
      Improvements in the timed up and go test and on the WOMAC pain and function
      scores, however, were restricted only to women who were classified as obese at
      baseline. These findings suggest that a 6-month weight loss and walking program
      improves measures of physical functioning and pain in overweight and obese
      postmenopausal women with knee OA. Among obese women, functional improvement
      correlated with weight loss, encouraging continued emphasis on weight loss for
      managing knee OA.

PMID- 17039139
TI  - Liver biopsy in psoriatic arthritis to detect methotrexate hepatotoxicity.
AB  - The use of methotrexate in the treatment of psoriatic arthritis is associated
      with risk of hepatotoxicity. However, monitoring of liver-associated enzymes
      often lacks sensitivity, and guidelines for serial liver biopsies in psoriatic
      arthritis are not yet well established. We performed a retrospective review of
      all patients with psoriatic arthritis receiving methotrexate who were enrolled in
      the disease-modifying anti-rheumatic drug clinics (DMARD clinics) at the Air
      Force and Army hospitals in San Antonio, Texas. Information was obtained
      regarding methotrexate regimen, liver-associated enzyme results, and liver biopsy
      results. Thirty psoriatic arthritis patients were taking methotrexate in the
      DMARD clinics. Seventeen patients had a total of 21 biopsies. Biopsies were
      performed for surveillance dictated by cumulative dose. Liver biopsies were
      graded on Roenigk scale of I-IV where I is mild steatosis, II is moderate
      steatosis, IIIa is mild fibrosis, IIIb is severe fibrosis, and IV is cirrhosis.
      Ten biopsies were grade I, 5 were grade II, 5 were grade IIIa, 1 was grade IIIb,
      and none were grade IV. In this very small retrospective study, regular
      monitoring of liver-associated enzymes did not correlate with histologic
      deterioration in our patients. Until prospective studies are performed, we
      suggest that routine liver biopsies are necessary to monitor for methotrexate
      hepatotoxicity in psoriatic arthritis.

PMID- 17039140
TI  - Skeletal manifestations of leprosy: analysis of 137 patients from different
      clinical settings in the pre- and post-modern treatment eras.
AB  - This study was conducted to further characterize the nature of leprosy-related
      bone alterations, to develop a hypothesis of their pathophysiology, and to define
      the impact of treatment on bone damage. Radiographs of 60 patients under care at
      the Carville, Louisiana leprosy hospital were compared with 50 from the early
      (before availability of effective treatment) part of this century and with 27
      from the Toronto (Ontario, Canada) leprosy clinic. Two-thirds of lesions were so
      severe that distal digital tufts had been lost to whittling, resorption, or
      fragmentation. Fifty percent were felt to be pathognomonic for the changes of
      leprosy. Resorption, fragmentation, and malaligned fractures are highly
      suggestive of leprosy, while diaphyseal whittling appears specific when medullary
      sclerosis or wavy diaphyseal borders are present. Medicinal intervention appeared
      to be of limited benefit for bone damage; perhaps greater attention to joint/bone
      protection (as recommended in diabetes management) will prove helpful.
      Environmental adjustment to minimize injury risk and daily limb examination for
      injury are recommended.

PMID- 17039141
TI  - Vasculitis following treatment of rheumatoid arthritis with extracorporeal
      staphylococcal protein a immunoadsorption column (prosorba).
AB  - We report a case of vasculitis after Prosorba treatment in a patient with
      rheumatoid arthritis. The patient is a 66-year-old white male with long standing
      rheumatoid arthritis and hepatitis B. He was treated with the standard regimen
      for Prosorba treatment. He improved and met criteria for an American College of
      Rheumatology (ACR) 20% response. While on therapy he developed a nonhealing
      ulcer. Approximately 2 weeks after treatment was completed, he developed palpable
      purpura and mononeuritis multiplex. Deep dermal biopsy confirmed the presence of
      both small and medium vessel vasculitis. Nerve conductions studies were
      consistent with neuropathic conduction delays. He was treated with 1mg/kg/day of
      oral prednisone. Prosorba has been reported to cause leukocytoclastic vasculitis
      during treatment, but has not been noted to involve medium sized vessels. This
      patient's history and presentation are most consistent with rheumatoid arthritis
      associated vasculitis, though the Prosorba treatment cannot be ruled out as a
      cause or a contributing factor. Importantly, although Prosorba treated his
      synovitis, it did not prevent concomitant vasculitis.

PMID- 17039142
TI  - Septic arthritis caused by Burkholderia pseudomallei: case report and review of
      the literature.
AB  - We describe a case of septic arthritis and bacteremia caused by Burkholderia
      pseudomallei, a bacterium that is endemic in East Asia and northern Australia. We
      believe that dissemination occurred in our patient after surgical excision of a
      pulmonary nodule. Bacteremic melioidosis can present with musculoskeletal
      involvement in 2-10% of patients, but septic arthritis is uncommon. A review of
      the literature shows a total of 66 patients reported with septic arthritis caused
      by this organism. Patients with septic arthritis caused by Burkholderia
      pseudomallei were likely to have diabetes mellitus, and the knee is the joint
      most frequently affected by this organism. Recommended initial treatment consists
      of ceftazidime, alone or in combination with trimethoprim/sulfamethoxazole, high
      dose imipenem/cilastatin, or high dose cefoperazone/sulbactam. This is followed
      by a 12-20 week course of oral therapy (based on susceptibilities) to eradicate
      the organism. Most patients with subacute or latent disease do well after full
      antibiotic treatment, but relapses are common if full treatment is not given.
      Awareness of this disease is important even in areas outside of Asia given the
      increasing frequency of international travel and the growing likelihood of
      imported cases, along with an aging population of Vietnam veterans and
      immigrants.

PMID- 17039143
TI  - Alveolar echinococcosis of the spine.
AB  - Alveolar echinococcosis (AE) is a rare parasitic disease caused by the larval
      stage of Echinococcus multilocularis. It differs from cystic echinococcosis
      caused by Echinococcus granulosus. The main endemic areas of AE are Alaska,
      Canada, Japan, and parts of Europe. Hepatic involvement invariably occurs, but it
      is unusual for bone to be affected. We report the case of a woman presenting with
      a long history of pain, cachexia, morning stiffness, and biological signs of
      inflammation. Radiographs and principally magnetic resonance images were
      nonspecific, showing inhomogeneous osteolysis of vertebral bodies without loss of
      intervertebral disc height but with a paravertebral mass. The diagnosis
      ultimately relied on pathological examination, which showed an anhistic laminated
      membrane colored in red with Periodic-Acid-Schiff surrounding a central cavity,
      and by the serologic testing, principally ELISA Em2(+) method, which allowed a
      97% specificity and 99% specificity in the diagnosis of AE. AE involving bone is
      an uncommon condition. Although magnetic resonance imaging can be used to search
      for local complications, the features it detects are, like those revealed by
      radiographs, nonspecific and can lead to AE being misdiagnosed as neoplasm or
      tuberculous osteitis. When a patient presents with suspected AE in an endemic
      area, the diagnosis can be achieved by serological testing alone (Western blot
      and Em2(+) ELISA), thereby avoiding the need for biopsy.

PMID- 17039144
TI  - Worsening of macrophage activation syndrome in a patient with adult onset Still's
      disease after initiation of etanercept therapy.
AB  - The macrophage activation syndrome (MAS) is a rare, potentially fatal, clinical
      syndrome, which has been described in childhood rheumatic disorders. MAS is
      defined by a prolonged period of fevers, pancytopenia, and hypertriglyceridemia
      (with or without hypofibrinogenemia). Histopathological examination of bone
      marrow, spleen, or lymph nodes shows hemophagocytosis by mononuclear phagocytes.
      In patients with Still's disease, observed triggering events for MAS have
      included both infectious processes and pharmacological agents, such as parenteral
      gold and nonsteroidal anti-inflammatory drugs. We report the case of a young
      woman with adult-onset Still's disease (AOSD), complicated by an Epstein-Barr
      virus infection and subsequent MAS, whose course worsened after administration of
      the soluble tumor necrosis factor-alpha receptor, etanercept. Subsequent
      treatment with pulse corticosteroids and cyclosporine A induced a dramatic
      clinical improvement. Treatment data regarding the use of etanercept in AOSD are
      lacking; given our experience and recent reports in children with Still's
      disease, we would suggest caution using this agent in patients with AOSD,
      particularly when complicated by MAS.

PMID- 17039145
TI  - Acute synovitis, fever and rash possibly caused by metallic debris from a
      loosened knee prosthesis in a patient with rheumatoid arthritis.
AB  - A 39-year-old woman with long-standing seropositive rheumatoid arthritis who had
      a total replacement of her left knee with a modular prosthesis in 1994 presented
      with fever, pruritic rash, and acute synovitis of that joint following local
      trauma. Synovial fluid showed a charcoal-like color, and contained abundant
      phagocytes laden with metal particles. In patients with rheumatoid arthritis who
      have undergone total joint replacement, metal particle reactions and possible
      hyper-sensitivity should be added to the list of potential causes of superimposed
      acute synovitis and systemic manifestations.

PMID- 17039146
TI  - Polymyalgia rheumatica and temporal arteritis with sacroiliitis and osteitis
      pubis.
AB  - Polymyalgia rheumatica (PMR) and temporal arteritis (TA) have been associated
      with a seronegative polyarthritis that can mimic rheumatoid arthritis.
      Sacroiliitis and osteitis pubis are most often encountered in the different types
      of spondyloarthropathy. However, sacroiliitis and osteitis pubis have rarely been
      described in patients with polymyalgia rheumatica and temporal arteritis. We
      present two patients, one with temporal arteritis and the other with polymyalgia
      rheumatica, who also had many features of a spondyloarthropathy, including
      sacroiliitis and osteitis pubis. In reviewing the literature, we found 30 other
      patients with a diagnosis of PMR who also had sacroiliitis and/or osteitis pubis.
      We propose that the inflammatory arthritis associated with polymyalgia rheumatica
      and temporal arteritis can involve the axial joints, resembling a
      spondyloarthropathy. It is important for the clinician to recognize that
      sacroiliitis and osteitis pubis have been associated with PMR and TA so that
      their radiographic presence does not dissuade the clinician from making the
      correct diagnosis.

PMID- 17039147
TI  - Pyogenic arthritis caused by capnocytophaga gingivalis in an immunocompetent
      three-year-old male.
AB  - Capnocytophaga gingivalis is most often isolated as normal oral flora or with
      periodontal disease. This organism is also associated with sepsis usually in
      immunocompromised hosts. We identified pyogenic arthritis caused by C. gingivalis
      in a 3-year-old immunocompetent male, whose clinical course closely resembled
      monoarticular onset pauciarticular juvenile rheumatoid arthritis. This is the
      first report of C. gingivalis septic arthritis in the world literature, but there
      are increasing reports of infections with this carbon dioxide-loving organism at
      other sites in non-immunocompromised individuals. The subacute presentation of
      the monoarthritis with this organism of low virulence led to a long delay in
      diagnosis and treatment. Any monoarthritis must continue to raise concern about
      infection.

PMID- 17039148
TI  - Renal microtophi in a patient with lupus nephritis and tophaceous gout.
AB  - This case describes a 58-year-old female with systemic lupus erythematosus (SLE)
      and coexistent chronic tophaceous gout. A renal biopsy showed concurrent lupus
      nephritis and renal medullary microtophi, confirmed by electron and polarizing
      microscopy, respectively. Whereas clinical SLE and gout have already been shown
      to be rarely associated, this case further illustrates the presentation of these
      two diseases in a single renal specimen. In this patient the gout began shortly
      after menopause without known risk factors and before any overt renal disease or
      signs of SLE. The tophaceous gout antedating the SLE, as well as the apparently
      benign course of illness, suggest that the pathologic effects of SLE and gout on
      the kidneys are based on independent mechanisms and may not necessarily aggravate
      each other. Treatment of the gout with allopurinol may have contributed to
      improved renal function.

PMID- 17039149
TI  - A report from the Mexican Congress of Rheumatology.

PMID- 17039150
TI  - Practice tip: improving zipper use with a key ring.

PMID- 17039152
TI  - Can parvovirus B19 infection trigger adult Still's disease? Report of a case
      controlled with infliximab.

PMID- 17039153
TI  - Inclusion body myositis unresponsive to etanercept.

PMID- 17039154
TI  - Should we be using more arthroscopy for septic arthritis?

PMID- 17039155
TI  - Treatment for JRA in the New Millennium.

PMID- 17039156
TI  - The Ehlers-Danlos syndromes: instructive for all cases of joint hypermobility?

PMID- 17039157
TI  - Failure to recognize CPPD disease as a cause of fever/mental status change: why
      does this happen?

PMID- 17039158
TI  - Intravenous immunoglobulin in pregnancies complicated by the antiphospholipid
      syndrome: what is its role?

PMID- 17039159
TI  - Current medication choices in juvenile rheumatoid arthritis II--update of a
      survey performed in 1993.
AB  - The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is
      important to allow for the evaluation of practice patterns for future outcome
      studies. A survey of nine pediatric rheumatologists was performed between
      September 1999 and February 2000. Each of the physicians prospectively recorded
      demographic and treatment information on consecutively sampled JRA patients
      (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in
      35%, and systemic onset JRA in 19% of the children. Naproxen was the most
      frequently prescribed medication (55% of the patients), followed by methotrexate
      (MTX), which was used in 39% of the patients. Folic acid supplementation (1
      mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used
      in 11% of the children. Eleven percent of the patients received corticosteroids,
      and 13% of children on corticosteroids took calcium supplements. Uveitis was
      present in 8% and had a chronic course in 79% of those cases. Although systemic
      medications were used in 50% of the children with uveitis to control eye
      inflammation, severe damage to the eyes developed in 30% of them. Fourteen
      percent of the patients required gastroprotective medications. Compared with
      findings of a similar survey performed in 1993, there was no significant change
      in the frequency of use of naproxen, but nabumetone is now more often prescribed,
      and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among
      second-line agents used for JRA have also occurred, although there was no change
      in the frequency of use of MTX or corticosteroids. JRA continues to be a
      treatment challenge for the practicing pediatric rheumatologist. Patients often
      show incomplete response to the currently available medications. Therefore, new
      therapeutic agents need to be evaluated for their use in JRA, and the treatment
      of JRA associated uveitis especially needs to be improved.

PMID- 17039160
TI  - Adult onset Still's disease: clinical features and outcome in 16 Thai patients.
AB  - The clinical features of adult onset Still's disease (AOSD) have rarely been
      described in Thai patients. We report the clinical manifestations, laboratory
      findings, and outcome of 16 Thai patients with AOSD, and compare these findings
      with those of the western and other oriental series. Fourteen patients (87.5%)
      had the onset of their disease between 16-35 years of age. The most common
      features presented were fever (100%), arthralgia and myalgia (100%), significant
      weight loss (84.6%), arthritis (81.3%), skin rashes (68.8%), sore throat (62.5%),
      elevated erythrocyte sedimentation rate (100%), leukocytosis (93.8%), and liver
      dysfunction (75%). Pleuro-pericarditis and abdominal pain were uncommon. All but
      2 patients required corticosteroids to control their systemic disease activity.
      The clinical course of 13 patients, who were followed for more than 12 months,
      was monocyclic systemic disease in four cases, polycyclic systemic disease in
      five, chronic articular monocyclic systemic in one, and chronic articular
      polycyclic systemic in three. When compared with western and other oriental
      series, the AOSD in Thai patients shared similar clinical features and laboratory
      findings, suggesting that mechanisms of pathogenesis may be similar in patients
      from widely different genetic backgrounds and geographic locations.
      Corticosteroids were frequently required and dramatically effective.

PMID- 17039161
TI  - Symptoms and functional health status of individuals with Ehlers-Danlos syndrome
      (EDS).
AB  - Ehlers-Danlos syndrome (EDS) is an inherited connective tissue disorder that can
      have a substantial impact on daily life. The aims of this study were to describe
      the symptoms reported in a group of individuals with EDS and to investigate the
      impact on functional health status by means of the Sickness Impact Profile (SIP).
      Seventy-seven individuals, members of the Swedish EDS Association, completed 2
      mailed questionnaires. The most frequent symptoms were related to activity, e.g.,
      joint problems (75%), to pain (71%), and to skin/tissue (52%). Pain was reported
      by 37 individuals (48%) as their most severe symptom. The SIP results showed an
      overall mean score of 13.0 (females 13.9, males 5.6), compared with a Swedish
      reference group with a SIP score 1.3. Women with EDS reported a better functional
      health status than females with rheumatoid arthritis (overall SIP score 13.9
      versus 21.4). In comparison with women with fibromyalgia, the EDS females rated
      their functional health status as worse on the physical dimension (p <0.05) and
      the subscale home management (p <0.05), and as better on the subscale work (p
      <0.05). Impact of EDS on the individual's daily life needs to be acknowledged,
      assessed, and evaluated in healthcare.

PMID- 17039162
TI  - Bone mineral density and bone turnover markers in a group of male ankylosing
      spondylitis patients: relationship to disease activity.
AB  - Conflicting data have been published about osteoporosis and bone turnover markers
      in patients with ankylosing spondylitis (AS). The aim of this study was to
      determine bone mineral density (BMD) of the lateral lumbar spine in a group of
      male patients with AS and to investigate the relationship between clinical
      parameters and markers of bone turnover. Thirty-two consecutive AS patients with
      a mean disease duration of 14.8 years and 32 control subjects were included.
      Demographic and clinical characteristics were recorded. The Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) was used to determine the activity of
      disease. BMD was determined for the lateral lumbar spine in both patients and
      control groups. Serum osteocalcin and urinary N-telopeptide were measured as bone
      turnover markers in patient and control groups. Although the mean values of
      lumbar BMD in AS patients tended to be lower than in the control group, the
      difference was not statistically significant. Osteoporosis was observed in 11
      (34.3%) of AS patients and in 2 (6.2%) of the control group. Osteocalcin levels
      were significantly higher in AS patients in comparison with control subjects (p <
      0.05). In the subgroup analysis according to the activity of the disease,
      erythrocyte sedimentation rate and N-telopeptide levels were significantly higher
      in the severely active group when compared with that in mild or moderate disease
      groups. Active AS patients compared with the control group had significantly
      lower BMD and significantly higher N-Telopeptide levels (p < 0.05). The levels of
      BASDAI scores and N-telopeptide values correlated significantly with each other.
      The incidence of osteoporosis is high in AS patients, and patients with active
      disease are especially at risk for developing osteoporosis. The monitoring of
      bone turnover markers and disease activity indices may help to predict patients
      at risk. Prophylactic and therapeutic strategies are needed to struggle against
      bone loss in patients with this disabling condition.

PMID- 17039163
TI  - Fever with acute arthritis in calcium pyrophosphate dihydrate deposition disease:
      a missed explanation for altered mental status in elderly patients?
AB  - Calcium pyrophosphate dihydrate (CPPD) deposition disease is a relatively common
      condition primarily affecting the elderly. Various clinical presentations ranging
      from an acute arthritis resembling gout (pseudogout) to fever of unknown origin
      have been reported. We describe four elderly patients with fever and altered
      mental status. Each patient underwent an extensive unrevealing work-up. An acute
      arthritis missed by the health-care team in their initial evaluation was later
      identified, leading to rheumatologic consultation and subsequent diagnosis of
      CPPD disease after joint aspiration and synovial fluid analysis. Defervescence
      and resolution of mental status changes occurred after improvement of the
      arthritis. Awareness that CPPD disease may present with systemic symptoms,
      including fever and altered mental status, may assure careful examination of
      joints and can prevent unnecessary testing and diagnostic delay.

PMID- 17039164
TI  - Acute motor-sensory axonal neuropathy associated with active systemic lupus
      erythematosus and anticardiolipin antibodies.
AB  - Acute motor-sensory axonal neuropathy (AMSAN) is an axonal variant of Guillian
      Barre syndrome (GBS) that presents with acute ascending quadriparesis. This has
      generally been described in association with Campylobacter jejuni infections or
      with anti-ganglioside antibodies. Known cases have shown a slow recovery and a
      poor prognosis. We report a case with clinical and electrophysiological evidence
      of AMSAN in association with active systemic lupus erythematosus (SLE) and
      anticardiolipin antibodies but not the other associations, with a rapid response
      to combination immunosuppressant and intravenous immunoglobulin (IVIg) therapy.
      The association between AMSAN and SLE has not been previously described. This
      case illustrates that early recognition and the utilization of electrophysiologic
      techniques may be beneficial in the diagnosis and management of GBS associated
      with SLE. Fulminant or rapidly progressive cases should be managed in specialized
      intensive care units. Combination therapy of immunosuppressants and IVIg may be
      beneficial in non-vasculitic axonal radiculo-neuropathies associated with SLE,
      resulting in good outcomes.

PMID- 17039165
TI  - Polymyositis evolving after rhabdomyolysis associated with HMG-CoA reductase
      inhibitors: a report of two cases.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are commonly
      used for treatment of hyperlipidemia and its deleterious effects. Myotoxicity has
      been associated with use of these agents. We report two cases of inflammatory
      myopathy in patients receiving these agents that did not respond to drug
      withdrawal and required immunosuppressive treatment. One of these patients
      developed an antibody to histidyl tRNA synthetase or Jo-1, an autoantibody
      associated with idiopathic inflammatory myopathies. We suggest that HMG-CoA
      reductase inhibitor-associated myotoxicity may trigger an immune-mediated
      inflammatory myopathy. Patients whose muscle abnormalities do not resolve with
      drug withdrawal should be considered for muscle biopsy.

PMID- 17039166
TI  - Intravenous immunoglobulin to prevent recurrent thrombosis in the
      antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) occurs as a primary entity or in association
      with autoimmune diseases, malignancies, or medications. Conventional treatment
      for APS-associated thrombosis involves the use of anticoagulants such as aspirin,
      heparin, and warfarin. Alternative treatment options are limited. We report on a
      patient with APS who failed conventional therapy but had clinical improvement and
      a decline in anticardiolipin (aCL) antibody titers during treatment with monthly
      intravenous immunoglobulin (IVIg). Anticardiolipin antibodies IgG, IgA, and IgM
      were measured before initiating IVIg and before each subsequent infusion of IVIg.
      The patient was also evaluated for the presence of thromboses during the
      treatment period. IgG and IgA aCL levels were elevated initially, and there was a
      significant decrease in anticardiolipin IgG and IgA levels during treatment
      without further episodes of thrombosis. IVIg may be an alternative therapy for
      recurrent thrombosis in the antiphospholipid antibody syndrome.

PMID- 17039167
TI  - A case of atorvastatin combined toxic myopathy and inflammatory myositis.
AB  - Muscle toxicity is one adverse reaction reported with the use of 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). This toxicity
      may include asymptomatic elevations of muscle enzymes, weakness, myalgia, and
      myositis. High doses of statins, or the combination of statins with other anti
      cholesterol medications, increase the risk of toxicity. In addition, case reports
      of systemic and autoimmune reactions such as lupus, nephritis, vasculitis, and
      myositis, suspected to be associated with statins, have been reported. Our 76
      year-old patient demonstrates a case of serologically and biopsy-proven
      inflammatory polymyositis, combined with a statin toxic myopathy. His symptoms
      and enzyme abnormalities resolved with both the removal of the statin medication
      and the institution of immunosuppressive therapy. Investigation of muscle enzyme
      elevation and weakness that do not resolve with statin removal is warranted.
      Certain muscle biopsy findings, including mononuclear cell infiltrate,
      distinguish the etiology as inflammatory/possibly autoimmune and do not suggest
      statin myopathy.

PMID- 17039168
TI  - Pericardial effusion and cardiomyopathy following arthritis with parvovirus B19
      infection: response to intravenous immunoglobulin.
AB  - We describe a 65-year-old female who presented with arthritis involving the small
      joints of her hand, wrists, and knee, fever, rash, and leukocytosis. During the
      course of her illness, she developed elevated transaminases, myositis, bilateral
      pleural effusions, a large pericardial effusion compressing the right atrium, and
      cardiomyopathy with impaired left ventricular function. The patient had evidence
      of acute parvovirus B19 infection by serology, although parvovirus specific DNA
      sequences from peripheral white blood cells were negative by polymerase chain
      reaction. This illness raised concern about possible collagen vascular disease.
      Low titers of antinuclear antibodies were present transiently, and other
      autoantibodies were undetected. Treatment with intravenous immunoglobulin
      resulted in dramatic resolution of her disease manifestations. Pericardial
      effusion and cardiomyopathy may be rare sequelae of parvovirus B19 infection. The
      apparent improvement with intravenous immunoglobulin could have been related to
      clearance of infection or down regulation of host immune response.

PMID- 17039169
TI  - Coexistent lyme disease and parvovirus infection in a child.
AB  - Infectious diseases commonly cause illnesses that mimic rheumatic diseases. Both
      Lyme disease and Parvovirus B19 infections produce arthritis, rashes, and a
      systemic illness that may be thought to represent a chronic rheumatic disease. In
      the case presented, a child with both infections simultaneously exhibited
      arthralgias, aseptic meningitis, and a facial rash. The features of Lyme disease
      and Parvovirus B19 infection that may mimic systemic lupus erythematosus include
      a facial rash, often in a malar distribution, hematologic abnormalities,
      arthritis, neurologic disorders, and autoantibody positivity. Given the proper
      season and geographical location, one must consider the possibility of co
      infection with these two organisms, especially in those with atypical rheumatic
      complaints.

PMID- 17039171
TI  - Molecular biology and immunology for clinicians, 14: Antigen presenting cells-
      Class II.
AB  - Pivotal to immunity and auto-immunity is the ability of the human immune response
      to make antigen-specific responses, both cellular and humoral. T- and B-cells
      contain within themselves the ability to recognize and react to specific
      antigens, but they must be made aware of the presence of their target in the
      surrounding environment to respond. Turns out this part of the education of T
      cells (not B-cells, which are activated by specific antigens in a different
      manner) is provided by a large number of cells, all coming under the umbrella
      term: antigen-presenting cells. Understanding how these cells take up molecules
      from the environment or acquire protein molecules from the intracellular milieu,
      manipulate them, and then offer the modified material to engage potentially
      responding cells in an immunological educational conversation is crucial to
      understanding normal immune function and, of course, auto-immunity and other
      forms of immune dysregulation. In the broadest of terms, there are two sources of
      proteins: endogenous (produced within the cell) and exogenous (produced outside
      of the cell), and there are two not entirely mutually exclusive pathways involved
      in antigen processing and presentation. To decrease confusion between these two
      separate pathways antigens, I will proceed with a description of the latter in
      this paper and cover the former in the next paper in this series. So, now on to
      antigen processing and presentation of proteins.

PMID- 17039172
TI  - Practice tips: making a chair seat higher.

PMID- 17039174
TI  - The clinical spectrum of anti-insulin receptor antibodies and autoimmune disease.

PMID- 17039175
TI  - Psoriatic arthritis: genetics, immunology, and therapies.

PMID- 17039176
TI  - Open trial of leflunomide for refractory psoriasis and psoriatic arthritis.
AB  - Leflunomide was recently approved for the treatment of rheumatoid arthritis. Its
      role in the treatment of psoriasis and psoriatic arthritis is unclear. Twelve
      consecutive psoriatic arthritis patients who had not responded to at least one
      disease modifying anti-rheumatic drug (DMARD) were started on leflunomide alone
      or in addition to another DMARD. Global assessment of improvement in psoriasis
      and psoriatic arthritis by the treating rheumatologist was scored on a 0-3 scale.
      After 2-3 months of treatment, 8 patients had moderate to marked improvement in
      both psoriasis and psoriatic arthritis. The improvement in modified tender joint
      counts, patient's global assessments, and grip strengths was statistically
      significant. However, physicians' global assessments and the modified swollen
      joint counts did not reach a significant difference. Three patients whose
      toxicity necessitated the temporary discontinuation of the drug were able to
      resume the drug at lower dosage with clinical benefit. Leflunomide may prove to
      be a useful agent for the treatment of recalcitrant cases of psoriasis and
      psoriatic arthritis.

PMID- 17039177
TI  - The prevalence of insulin receptor antibodies in patients with systemic lupus
      erythematosus and related conditions.
AB  - Autoantibodies to the insulin receptor have been demonstrated to antagonize the
      physiologic actions of insulin, most often resulting in hyperglycemia
      unresponsive to massive doses of insulin (type B insulin resistance). Patients
      with these anti-insulin receptor antibodies typically have a coexistent
      autoimmune disorder, most commonly systemic lupus erythematosus (SLE) or
      undifferentiated autoimmune syndromes. Attempting to determine the prevalence and
      significance of anti-insulin receptor antibodies, sera from consecutive patients
      with SLE and early undifferentiated connective tissue disease (UCTD) were tested
      for the presence of anti-insulin receptor antibodies by radio-immuno assay.
      Thirty-eight patients participated in the study. Twenty-six had SLE and 12 had
      UCTD. One patient with SLE (2.6%) was positive for anti-insulin receptor
      antibodies. None of the patients demonstrated evidence of insulin resistance,
      hypoglycemia, ovarian hyperandrogenism, or acanthosis nigricans, findings
      commonly linked with the presence of anti-insulin receptor antibodies. The
      results presented here indicate that the incidence of anti-insulin receptor
      antibodies in patients with SLE or UCTD, without associated history of altered
      glucose metabolism, is quite low. Because in most cases the disturbance of
      glucose metabolism dominates the clinical picture at presentation and the
      associated systemic autoimmune syndrome presents either simultaneously with or
      subsequent to the diagnosis of diabetes, the measurement of anti-insulin receptor
      antibodies should be reserved for patients with indications of disordered glucose
      homeostasis.

PMID- 17039178
TI  - Colchicine induced neuromyopathy in a patient with normal renal function.
AB  - A 69-year-old male on colchicine 0.6 mg twice a day for more than a year
      developed subacute onset of painless proximal muscle weakness with significant
      elevation of creatine phosphokinase (CPK) levels. He also experienced numbness
      and tingling in the extremities. Nerve conduction studies revealed a mild axonal
      neuropathy affecting the arms and legs while needle electromyography was
      unremarkable. He refused a muscle biopsy. After withdrawal of colchicine, muscle
      strength and serum CPK levels returned to normal over a period of 4 months.
      Neuromyopathy is a well documented side effect of colchicine, and impaired renal
      function has been the major risk factor in previously reported cases. In our
      patient, neurological toxicity occurred in the presence of normal renal function.
      The neuromyopathy is generally reversible on withdrawal of the drug. Colchicine
      is to be used with caution in patients with impaired renal function, and even if
      kidney function is normal, muscle strength must be monitored and serum CPK levels
      checked if myopathy is suspected.

PMID- 17039179
TI  - Aplastic anemia in systemic lupus erythematosus: a distinct presentation of
      acquired aplastic anemia?
AB  - Aplastic anemia is a rare but serious complication of systemic lupus
      erythematosus (SLE) with an often dramatic and unanticipated onset. The
      peripheral destruction of formed blood elements, which frequently accompanies the
      syndrome, may obscure or delay the diagnosis of bone marrow suppression, and the
      number of published cases may be an underestimate of the actual incidence of the
      disease. Furthermore, the disease course may differ significantly from other
      forms of acquired aplastic anemia and seems to carry a more favorable prognosis
      once effectively diagnosed and treated. In addition, aplastic anemia may precede
      other manifestations of SLE. Therefore, the possibility of bone marrow aplasia
      should be excluded in all SLE patients with severe pancytopenia, and conversely,
      the diagnosis of SLE should be explored in cases of aplastic anemia. Two patients
      with aplastic anemia in SLE, one with aplastic anemia preceding the onset of SLE,
      are described along with 15 cases reviewed from the English language literature.
      The presentation, prognosis, treatment, and pathogenesis of aplastic anemia
      complicating SLE are discussed. Recognition that cytopenias, especially
      pancytopenia, may occur on the basis of inhibited myelopoesis rather than
      peripheral destruction as either a harbinger of SLE or as a manifestation of
      disease flare is important. This knowledge will prompt the astute clinician to
      obtain screening antinuclear antibodies in the setting of otherwise unexplained
      bone marrow acellularity or, given the prognosis of SLE associated aplastic
      anemia, give early consideration to more aggressive immunosuppression.

PMID- 17039180
TI  - Cytomegalovirus esophagitis as a treatable complication of systemic sclerosis.
AB  - We report the case of a 51-year-old woman with a connective tissue disease of 8
      years duration. She had been taking corticosteroids at a dose of 1 mg/kg/day and
      azathioprine at a dose of 3 mg/kg/day for 1 month. Given the clinical suspicion
      of systemic sclerosis (limited form of scleroderma), she was studied according to
      a protocol including endoscopy to assess the degree to which the underlying
      disease had affected the gastrointestinal tract. Endoscopy revealed a
      asymptomatic severe esophagitis and a subsequent biopsy disclosed the presence of
      cytomegalovirus. Cytomegalovirus pneumonia was also detected. Both processes were
      successfully managed with intravenous ganciclovir (5 mg/kg/12 hr) for 21 days.
      This report is a case of cytomegalovirus involving the esophagus in association
      with systemic sclerosis in a patient immunosuppressed because of drugs that she
      had been taking. This complication can be asymptomatic and is amenable to
      treatment.

PMID- 17039181
TI  - Pulmonary Takayasu's arteritis masquerading as acute pulmonary embolism.
AB  - Pulmonary involvement may sometimes be the initial presentation of Takayasu's
      arteritis (TA). Since the signs and symptoms of pulmonary TA may be subtle and
      may not be easily distinguishable from other pulmonary diseases, one has to
      maintain a high index of suspicion. Cases of pulmonary TA mimicking chronic
      thromboembolism have been reported. We describe a patient with TA whose initial
      presentation mimicked acute pulmonary embolism. The patient presented with a 3
      day history of cough and shortness of breath and had multiple bilateral perfusion
      defects on ventilation-perfusion scan, typical of acute pulmonary embolism.
      However, the constellation of clinical features, elevated erythrocyte
      sedimentation rate and the angiographic appearance helped us establish the
      correct diagnosis of pulmonary Takayasu's arteritis. At a 6-year follow-up, the
      patient had no worsening of pulmonary symptoms but presented with postural
      dizziness with angiographic evidence of carotid and innominate artery stenosis;
      she underwent arterial bypass grafting. In young women presenting with a clinical
      picture of acute pulmonary embolism without the previous history (or risk
      factors) of thromboembolism, pulmonary TA must be considered in the differential
      diagnosis.

PMID- 17039182
TI  - A muscle mass in a patient with polymyalgia rheumatica.
AB  - We report the extremely uncommon case of a 77-year-old woman in whom a tumor
      found to be a melanotic schwannoma, arising from the right rectus abdominis
      muscle, was detected during investigation for a rheumatic disorder, finally
      identified as polymyalgia rheumatica (PMR). Tumors of this type most commonly
      occur in spinal nerve roots, and their clinical behavior is very difficult to
      predict. As far as we are aware, this is the first reported case affecting the
      aforementioned site. The challenging issue in this case concerns the possible
      link between the 2 clinical conditions, in particular the development of PMR as a
      paraneoplastic syndrome. Although such an association has not been reported, PMR
      is included among the rheumatic disorders reported to be associated with
      malignancies and occasionally with benign tumors. However, given that tumor
      resection did not result in remission of PMR and symptoms improved rapidly with
      prednisone, it seems likely that the above disorders might simply coexist.

PMID- 17039183
TI  - Minor salivary gland punch biopsy for evaluation of Sjogren's syndrome.
AB  - Incisional biopsy of labial salivary glands has been a valuable technique for
      diagnosis of Sjogren's syndrome. This report describes a new technique using
      punch biopsies that requires fewer resources and appears to be equally effective.
      Fifty patients evaluated by punch biopsy all yielded adequate pieces averaging 6
      glands per specimen. Two patients had transient numbness of the lip. There were
      no other complications. Classical findings of Sjogren's histopathology were
      demonstrable with these specimens. This technique is safe, less expensive, and is
      proposed as a reliable alternative to incisional biopsy.

PMID- 17039184
TI  - Periostitis in a patient with ulcerative colitis.

PMID- 17039185
TI  - Molecular biology and immunology for clinicians 15: Antigen presenting cells-
      class I.
AB  - Class I-bearing antigen presenting cells (APCs) monitor intracellular proteins
      which are cellular proteins made on a routine basis, endogenous proteins made by
      stressed cells, proteins made by infected or transformed cells, or proteins made
      by intracellular pathogens, e.g., viruses, chlamydiae, mycoplasma, Listeria, and
      some Enterobacteriaceae. The mechanisms by which peptides interact with and are
      expressed by class I complexes on the surface of APCs is described and contrasted
      with the circumstances of class II antigen presentation.

PMID- 17039186
TI  - Practice tips: teaching aid for bursitis.

PMID- 17039188
TI  - Life-threatening hypokalemic paralysis and hypophosphatemic myopathy as initial
      presentations of primary Sjogren's syndrome.

PMID- 17039189
TI  - What really is Poncet's disease? Report of a case mimicking sarcoidosis.

PMID- 17039190
TI  - Acute renal failure can occur with inappropriate use of a coxib.

PMID- 17039191
TI  - The ever-expanding clinical spectrum of tuberculosis.

PMID- 17039192
TI  - SAPHO: disease, syndrome, or category?

PMID- 17039193
TI  - Should rheumatologists be evaluating acupuncture?

PMID- 17039194
TI  - Acupuncture improves peripheral perfusion in patients with reflex sympathetic
      dystrophy.
AB  - Patients with stage II reflex sympathetic dystrophy syndrome (algodystrophy)
      often describe a sensation of beneficial warmth in the affected limb when
      receiving acupuncture treatment. In a case control study of 10 patients with
      unilateral algodystrophy stage II, and 10 healthy sex and age-matched controls,
      we investigated whether acupuncture has an effect in blood volume flow and
      correlated this with a clinical assessment. Blood volume flow was measured by
      duplex sonography before, during, and after acupuncture. During acupuncture,
      blood volume flow increased significantly (+31.1%, p (one-tailed) = 0.024) in the
      patients' effected limbs (by algodystrophy) compared with the patients' untreated
      limbs (contralateral). It was also elevated compared with the controls' treated
      limbs (+23.9%, p = 0.046). The corresponding data after acupuncture were +29.5%,
      p = 0.057 and +38.3%p = 0.014. All but one patient reported improved symptoms.
      However, only subjective improvement in function, not pain, was positively
      correlated to the increase in blood volume flow. In patients with algodystrophy
      stage II, a significant increase of blood volume flow was attributed to
      acupuncture and was correlated to functional improvement.

PMID- 17039195
TI  - A study of musculoskeletal manifestations in 12 patients with SAPHO syndrome.
AB  - Synovium and synovial fluid findings in SAPHO (synovitis, acne, pustulosis,
      hyperostosis, and osteitis) syndrome have not been well characterized, and only a
      few patients have been described in the Americas. We describe clinical,
      pathologic, and synovial fluid findings in 12 patients with the SAPHO syndrome:
      hidradenitis suppurativa (7), acne fulminans or conglobata (3), acneiform
      folliculitis (1) and palmoplantar pustulosis (1). Routine synovial fluid studies
      were performed in 6 patients, and light and transmission electron microscopic
      studies were performed in synovium in 2 patients and in bone in 1. The most
      common musculoskeletal manifestations included erosive or non-erosive
      oligoarthritis involving metacarpal phalangeal (MCP) and metatarsal phalangeal
      (MTP) joints as seen in 9 patients, sclerosis of the sacroiliac joints as seen in
      5 patients, and osteitis pubis as seen in 1. Three patients had signs of skeletal
      hyperostosis. The patients with acne fulminans and acneiform folliculitis had
      chronic aseptic multifocal osteomyelitis. Synovial fluid was sterile in 7, mildly
      inflammatory in 5, and highly inflammatory in 2. Electron microscopic studies of
      synovium in 2 patients and of bone in 1 were not useful to detect microorganisms.
      Three African-American patients with hidradenitis suppurativa presented with
      pyoderma gangrenosum, and 2 of them had leukocytoclastic vasculitis, and a life
      threatening course unresponsive to antibiotics, corticosteroids and
      immunosuppressive therapy. SAPHO in the Americas is most severe in African
      Americans with hidradenitis suppurativa, and it presents with heterogeneous
      musculoskeletal and cutaneous manifestations including erosive polyarthritis or
      oligoarthritis with nonspecific mild inflammatory fluid. Leukocytoclastic
      vasculitis and recalcitrant pyoderma gangrenosum were seen in 2 of our patients
      with the most severe hidradenitis suppurativa. SAPHO syndrome may present with
      clinical manifestations similar to those seen with seronegative
      spondyloarthropathies, but it has distinctive cutaneous, radiographic articular,
      and bone manifestations. Sites of chronic infection need aggressive antibiotic
      therapy and may need surgical resection.

PMID- 17039196
TI  - Prevalence and predictors of cervical involvement in psoriatic
      spondyloarthropathy.
AB  - Cervical spondylitis has been reported in 35%-75% of patients with psoriatic
      arthritis (PsA), and this likely represents the highest frequency of cervical
      involvement among the spondyloarthropathies. Although 2 patterns of cervical
      spondylitis have been recognized in PsA, this may reflect a lack of a
      satisfactory definition of cervical spondylitis in PsA. In a retrospective cross
      sectional study, we analyzed the clinical records of 100 consecutive patients
      recruited at a single university hospital who were diagnosed as having psoriatic
      spondyloarthropathy on the basis of radiographic sacroiliitis. All patients were
      involved in a clinicoradiologic study of the cervical column to evaluate the
      frequency and the predictors of this involvement. Forty-one patients showed
      radiographic signs of cervical involvement and 24 of them (58.5%) complained of
      cervical pain and stiffness, whereas 17 (41.5%) had radiologic disease with no
      symptoms. Arthritis duration (odds ratio, 1.08; 95% confidence interval, 0.99
      1.19; p < 0.05) and peripheral erosive disease (odds ratio, 2.5; 95% confidence
      interval, 1.91-6.92; p < 0.05) were found to be associated with cervical
      spondylitis development. This study showed a high frequency of cervical
      spondylitis among patients with psoriatic spondyloarthropathy, confirming
      previous reports. Although none of our patients developed neurologic sequelae,
      this report also showed that clinical symptoms of cervical pain and stiffness are
      not a universal predictor of involvement of the cervical spine, and therefore,
      patients with PsA with longer disease duration and erosive disease should be
      screened radiologically to detect those cervical lesions (i.e., atlantoaxial
      subluxation) with potential catastrophic complications.

PMID- 17039197
TI  - Pathologic fracture of the femoral neck in a female soccer player.
AB  - We report a case of a healthy, young, female soccer player who developed
      progressive pain in her right hip. A bone cystic lesion was found in the right
      femoral neck and proximal femur. The lesion was considered a benign bone cyst and
      the patient was treated with injections of autologous bone marrow and grafting
      into the femoral neck. However, the cystic lesion did not heal. Subsequently, the
      patient fell and developed a fracture of the femoral neck that required internal
      fixation. The bone biopsy showed characteristic histologic features of fibrous
      dysplasia. A bone scan showed other areas of suspected dysplasia. Pamidronate
      therapy was given, and a reduction of the increased uptake was seen on bone
      scans. Fibrous dysplasia must be considered in the differential diagnosis of any
      cystic bone lesion.

PMID- 17039198
TI  - Multifocal tubercular dactylitis in an adult.
AB  - Musculoskeletal tuberculosis (TB) is a rare manifestation of TB comprising 1%-3%
      of all cases. We describe a patient who had multiple manifestations of skeletal
      TB, including spondylitis, dactylitis, and Poncet's disease. The unusual features
      include multifocal dactylitis, widespread disease in the absence of any risk
      factor like HIV infection or immunosuppressive treatment, and absence of
      pulmonary lesion. Treatment with appropriate drugs, using 4 agents for the first
      2 months, led to complete recovery. TB can rarely present in an unusual way but
      is very important to recognize, as with treatment it still carries a good
      prognosis.

PMID- 17039199
TI  - Disseminated Histoplasmosis Mimicking Felty's Syndrome.
AB  - The successful treatment of rheumatoid arthritis often requires the use of
      immunosuppressive medications. Although these agents have different potential
      toxicities, they share in common the potential for permitting the development of
      opportunistic infections. We describe 2 patients with chronic rheumatoid
      arthritis treated with immunosuppressive agents who developed progressive
      neutropenia with documented splenomegaly. The differential diagnosis included
      Felty's syndrome versus bone marrow suppression from their immunosuppressive
      medication. Although both patients had the triad of Felty's syndrome, high titer
      seropositive rheumatoid arthritis with splenomegaly and neutropenia, the
      diagnosis of this syndrome relies on excluding other potential causative factors.
      Further investigation revealed that both patients had disseminated histoplasmosis
      with bone marrow involvement, which most likely represented reactivation from
      prior exposure to Histoplasma capsulatum. Opportunistic infections such as
      disseminated histoplasmosis can mimic other disease processes, including Felty's
      syndrome, and are important to consider when there is a change in the clinical
      status of patients with rheumatic disease who are immunocompromised.

PMID- 17039200
TI  - Hepatitis C virus infection, inflammatory myopathy, and pulmonary fibrosis: are
      they related?
AB  - We describe the clinical findings, laboratory and ancillary studies, and
      histopathologic findings of 2 patients with hepatitis C virus infection who
      developed inflammatory myopathy and interstitial lung disease. A review of
      pertinent literature revealed several other patients with a similar cluster of
      clinical manifestations. The inflammatory myopathy in the cases reported here was
      atypical and distinct from that found in the anti-synthetase syndrome because it
      was characterized by mild or intermittent elevation of creatine phosphokinase,
      absence of anti-JO1 antibodies, and excellent response to oral corticosteroids.
      Thus, this report supports the hypothesis that hepatitis C virus infection may
      cause both inflammatory myopathy and pulmonary fibrosis. We suggest that
      evaluation for hepatitis C virus infection should be pursued in all patients with
      inflammatory myopathy and pulmonary fibrosis irrespective of anti-JO1 status. We
      further suggest that hepatitis C should be considered as another cause of
      myositis and interstitial lung disease in addition to the anti-synthetase
      syndrome.

PMID- 17039201
TI  - Drug-induced amyopathic dermatomyositis.
AB  - Amyopathic dermatomyositis is a rare condition. We describe the clinical and
      histopathologic findings of a 53-year-old woman who developed cutaneous lesions
      similar to those described in dermatomyositis after fibrate therapy for
      hypertriglyceridemia. Our patient fits the proposed criteria for amyopathic
      dermatomyositis, and after 8.5 years, muscular involvement has not been detected,
      although the dermatologic lesions are still present despite different treatments
      reported to treat this condition (steroids, antimalarials, methotrexate,
      dapsone). However, an initial good response has been observed with thalidomide, a
      drug used increasingly in the dermatologic field. As far as we know, this case is
      the first of drug-induced amyopathic dermatomyositis.

PMID- 17039202
TI  - Persistent back pain after a fall.

PMID- 17039205
TI  - Fever and knee effusions.

PMID- 17039203
TI  - Molecular biology and immunology for clinicians 16: Dendritic cells and their
      role in immunology.
AB  - As is so often the case in immunology, with the passage of time and further
      research, cells of obscure lineage and function become the darlings of the field.
      Such is the case with dendritic cells. Probably the most potent antigen
      presenting cells of all, dendritic cells are pivotal in the education and
      coaching of T-cells, B-cells, and natural killer cells, putting the dendritic
      cell firmly in place to influence both innate and antigen-specific immune
      reactivity. Thus, understanding dendritic cells' function and how they switch
      morphologically and functionally during their maturation may be very important if
      we are to manipulate dendritic cells to suppress or enhance immunologic function
      in disease. There is sure to be more about dendritic cells in the oncology,
      clinical immunology, and rheumatology literature over the coming years as we
      learn to control dendritic cell function.

PMID- 17039206
TI  - Practice tips: relief of sciatica with a foot rest.

PMID- 17039208
TI  - Pneumocystis carinii pneumonia associated with leflunomide therapy for rheumatoid
      arthritis.

PMID- 17039209
TI  - The diagnosis of systemic lupus erythematosus.

PMID- 17039210
TI  - Drugs for treatment of ADHD.

PMID- 17039211
TI  - Usefulness of disability to sub-classify chronic low back pain and the crucial
      role of rehabilitation.

PMID- 17039212
TI  - General Medicine and Rehabilitation: bio-psycho-social answers to back pain in
      its different stages.

PMID- 17039213
TI  - Falls in a rehabilitation setting: functional independence and fall risk.
AB  - AIM: With this study we wanted to determine the incidence, characteristics and
      consequences of falls in our rehabilitation setting. METHODS: An observational
      study was carried out in a rehabilitation setting for postacute orthopedic and
      neurological inpatients. Three-hundred and twenty patients were enrolled. Falls
      risk factors (Downton index [DI] and other known parameters), disability
      (functional independence measure [FIM]) and balance (Berg balance scale [BBS])
      were assessed at admission. Falls that occurred during the rehabilitation stay
      were prospectively classified (St. Louis Older Adult Service and Information
      System [OASIS] system) and analyzed. RESULTS: Forty patients experienced a fall
      (12.5%). The faller group was characterized by a major clinical complexity; 70%
      of fallers were neurological patients and 30% presented cognitive impairment
      (mini mental state examination [MMSE] <24). They presented a statistically
      significant worse score on FIM (motor and cognitive), BBS and DI at admission,
      with 74% predictability of falls as measured by total FIM score and age. Falls
      recorded with the OASIS classification showed a prevalence (52.5%) for not
      bipedal (wheelchair transfer) and self-generated falls; 35% were intrinsic falls
      (caused by subject-specific factors) and 12.5% extrinsic falls (caused by
      environmental factors). Falls resulted in only minor clinical consequences,
      except for one rib fracture, but led to a significant increase in length of stay.
      CONCLUSIONS: In a rehabilitation centre, for good management of resources and
      safe prescriptions of a patient's independence in activities of daily living,
      fall risk is better evaluated with appropriate scales.

PMID- 17039214
TI  - Biomechanics of lower limb raising from the supine position.
AB  - AIM: This study analyses the kinematics of the lower limb raising movement from
      the supine position and the electromyography activity of the muscles involved.
      METHODS: Twenty healthy right hand subjects performed the right lower limb
      raising from the supine position, starting from the clinical bed plane and up to
      a 70 degrees inclination of the thigh over the horizontal plane, while the knee
      was kept flexed at 120 degrees by a soft splint. The same exercise was executed
      with no resistance and with 2 kg and 8 kg respectively applied to the ankle. The
      kinematics was recorded utilising an optoelectronic system, whereas the
      electromyography activity was recorded by a surface electromyography (EMG)
      applied to the following muscles: right rectus femoris, left biceps femoris,
      rectus abominalis from both sides and dorsal major from both sides. RESULTS: In
      all the cases the pelvis performed a backwards rotation retroversion. The highest
      increase of EMG activation was recorded on the right rectus femoris as well as on
      the left biceps femoris; the increase was lower in the right rectus abdominis and
      in the right dorsal major, whereas it was minimum in the left rectus abdominis
      and in the left dorsal major. A great variability in the activation times was
      reported in the various muscles of the different subjects, regardless of the
      trials. The only muscle anticipating the right rectus femoris activation was the
      left biceps femoris. CONCLUSIONS: The research has shown how the simple movement
      under study is more complex than what is usually described by the text books,
      both in regard to the kinematics and to muscles' actions. Even the individual
      variability in utilising the agonist and stabilisation muscles can be of
      relevance for a more rational utilisation of the physical exercise in motor re
      education.

PMID- 17039215
TI  - Pain relief in early rehabilitation of rotator cuff tendinitis: any role for
      indirect suprascapular nerve block?
AB  - AIM: The purpose of the trial was to evaluate the efficacy of suprascapular nerve
      block (SSNB) to relieve the shoulder pain, ameliorate recovery after
      physiotherapy and reduce disability due to a rotator cuff tendinitis (RCT). A
      prospective, randomized, comparison cross over investigation was performed in the
      setting of a large inpatient rehabilitation unit with more than 200 admissions
      annually. METHODS: A total of 40 potential study subjects, who complained of
      shoulder pain from a RCT, were enrolled and randomly assigned to standard
      rehabilitation treatment plus SSNB (Group A) or to standard rehabilitation
      treatment alone (Group B). The UCLA shoulder rating scale was used to assess the
      shoulder mobility on admission and discharge, and to calculate the percentage of
      potential improvement achieved during rehabilitation (effectiveness). A pain
      visual analogic scale was used to serially assess pain. At the end of the trial,
      a self-report questionnaire evaluated whether patients could sleep and achieve
      activity of day life carry out everyday activities better than they could before
      treatment. RESULTS: Forty patients suffering from RCT entered the study. Those
      receiving nerve block from the beginning of the treatment in addition to standard
      rehabilitation therapy reported significantly less pain during physiotherapy and
      better final outcomes. During treatment with SSNBs, patients reported a more
      significant reduction in the intensity of pain and a better reduction of pain
      during sleep and rehabilitation exercises in comparison to with the standard
      therapy alone. A statistically significant inverse correlation was found between
      shoulder pain and mobility. CONCLUSIONS: The results indicate that combining
      nerve block with standard rehabilitative therapy may improve the final outcome of
      painful RCT. It decreased the severity and frequency of the perceived pain,
      improved the compliance with physiotherapy, restored more normal sleep patterns,
      and increased compliance with the rehabilitation program. This result proves to
      be an effective, safe and inexpensive therapeutic option for patients suffering
      from painful disabling shoulder tendinitis.

PMID- 17039216
TI  - Two different techniques in the rehabilitation treatment of low back pain: a
      randomized controlled trial.
AB  - AIM: The Back School is a widely accepted and effective method for treating low
      back pain, whereas no scientific evidence exists about the effects of the Pilates
      CovaTech method. With this study we wanted to evaluate the efficacy of this new
      method in patients with low back pain. METHODS: Fifty-three patients with at
      least 3 months of nonspecific low back pain were entered into a Pilates therapy
      or a Back School treatment group, 43 of which completed the study. Small exercise
      groups of 7 patients each followed a daily kinesitherapy protocol for 10 days.
      Evaluations were performed at the start of the study and then at 1, 3 and 6
      months after the beginning of treatment. We used the Oswestry Low Back Pain
      Disability Scale (OLBPDQ) to assess disability and the visual analog scale (VAS)
      to evaluate pain. RESULTS: Demographic and baseline clinical characteristics were
      similar for both groups. A significant reduction in pain intensity and disability
      was observed across the entire sample. The Pilates method group showed better
      compliance and subjective response to treatment. CONCLUSIONS: The results
      obtained with the Pilates method were comparable to those achieved with the Back
      School method, suggesting its use as an alternative approach to the treatment of
      non specific low back pain.

PMID- 17039217
TI  - Follow-up in persons with traumatic spinal cord injury: questionnaire
      reliability.
AB  - AIM. The aim of this study is to show the compliance and the test-retest
      reliability of the questionnaire. METHODS: Construction of a structured
      questionnaire to perform a phone follow-up in 511 persons with traumatic spinal
      cord injury (SCI) 4 years after discharge from the first rehabilitative
      hospitalization. The questionnaire is structured in 24 items, comprising
      exclusion (closed questions) answers and 3 analogic scale answers, divided into 7
      aspects: clinical conditions, sentimental relationships, quality of life,
      autonomy, mobility, occupation, social reintegration. A pilot survey on 20
      subjects with SCI, hospitalized in different periods in 2 rehabilitation centers,
      was performed to check the questionnaire's feasibility and reproducibility. The
      persons were interviewed twice by telephone, with an interval of about one month,
      by a psychologist. The questionnaire was completed during one single phone
      conversation. RESULTS: No missing answers were recorded. The test run for this
      questionnaire showed high reproducibility based on the large numbers of questions
      with 100% correspondence between the answers ''before'' and ''after''. For most
      of the other questions this factor ranged between 80% and 99%, and for 2
      questions on the analogic scale between 30% and 50%. CONCLUSIONS: The data
      collected by this pilot survey show the reliability of this questionnaire for all
      answers, save for the quantification of subjective variables.

PMID- 17039218
TI  - Persistence of range of motion in dorsiflexion, when the triceps surae muscles
      weaken, worsens stance and gait in Charcot-Marie-Tooth disease. A case report.
AB  - Charcot-Marie-Tooth disease is a genetically heterogeneous disorder,
      characterized by length dependent degeneration of motor and sensory nerve fibers.
      The variability in clinical severity is typical, and is considered the result of
      environmental factors interacting with the genotype. We report the case of 2
      sisters who present the same muscle involvement, with complete atrophy below the
      knees, but a very different degree of disability: the milder affected sister can
      walk independently for 1 km, the more severe for 50 m only. The factor,
      responsible for the different functional impairment, is the persistence of ankle
      dorsiflexion. This is the result of prolonged stretching of the heel cords in the
      more severely affected sister, which destabilizes stance and ambulation. On the
      contrary, the milder affected sister presents a slight equinus deformity well
      compensated by wearing shoes with a bit of heel. The presented cases and
      biomechanics suggest that the persistence of range of motion in dorsiflexion,
      when the triceps surae muscles weaken beyond a certain degree, represents an
      important negative factor of clinical variability in Charcot-Marie-Tooth disease;
      this can be averted by correct rehabilitation management.

PMID- 17039219
TI  - The challenge of uncovering outcome in neurological rehabilitation.

PMID- 17039220
TI  - Quality of life and aphasia. Multicentric standardization of a questionnaire.
AB  - AIM: It is important to assess aphasics' quality of life in order to plan a
      rehabilitation treatment. To date such a tool is still missing for Italian
      patients. This paper reports normative data of the Italian version of SAQOL-39, a
      British questionnaire aimed to assess aphasics' quality of life. It consists of
      39 items, divided into 4 subdomains (Physical, Communication, Psychosocial and
      Energy). METHODS: Forty-two patients coming from 3 different Speech Therapy
      Services were enrolled. All patients completed speech therapy before examination.
      They were submitted to the Italian SAQOL-39 and 2 screening tests for aphasia: 1)
      Communication Assessment Scale according Goodglass and Kaplan; 2) Franchay
      Aphasia Screening Test (FAST). A receptive FAST score of 7 out of 15 was used as
      a cut-off score for SAQOL-39 administration. RESULTS: The Italian SAQOL-39 showed
      good internal consistency (full scale Cronbach's alpha 0.939). Cronbach's alpha
      for every subdomains ranged from 0.950 (Communication) to 0.720 (Energy). Fluent
      aphasics gave significantly higher scores than nonfluent ones on full scale, and
      all out of Energy subdomains. Furthermore gravity of aphasia correlated with both
      full scale and Communication subdomain scores. CONCLUSIONS: In authors' opinion,
      the Italian SAQOL-39 shares many psychometric features with the English one. This
      questionnaire seems to be suitable for clinical practice.

PMID- 17039221
TI  - A randomised controlled cross-over trial of aerobic training versus Qigong in
      advanced Parkinson's disease.
AB  - AIM: To investigate the effects of an aerobic training in subjects with
      Parkinson's disease (PD) as compared to a medical Chinese exercise (Qigong).
      METHODS:  DESIGN: randomized controlled trial with a cross over design. SETTING:
      PD out-patients referred to a Neurorehabilitation facility for the management of
      motor disability. SUBJECTS: 26 PD patients in Hoehn and Yahr stage II to III
      under stable medication were randomly allocated to either Group AT1+QG2
      (receiving 20 aerobic training sessions followed by 20 ''Qigong'' group sessions
      with 2 month interval between the interventions), or Group QG1+AT2 (performing
      the same treatments with an inverted sequence). MAIN OUTCOME MEASURES: clinical
      effects of treatment were sought through the Unified Parkinson's Disease Rating
      Scale (UPDRS), Brown's Disability Scale (B'DS), six-Minute Walking Test (6MWT),
      Borg scale for breathlessness, Beck Depression Inventory (BDI) and Parkinson's
      Disease Questionnaire-39 items (PDQ-39). A spirometry test and maximum
      cardiopulmonary exercise test (CPET) were also performed to determine the
      pulmonary function, the metabolic and cardio-respiratory requests at rest and
      under exercise. All measures were taken immediately before and at the completion
      of each treatment phase. RESULTS: The statistical analysis focusing on the
      evolution of motor disability and quality of life revealed a significant
      interaction effect between group and time for the 6MWT (time x group effect: F:
      5.4 P=0.002) and the Borg scale (time x group effect: F: 4.2 P=0.009). Post hoc
      analysis showed a significant increase in 6MWT and a larger decrease in Borg
      score after aerobic training within each subgroup, whereas no significant changes
      were observed during Qigong. No significant changes over time were detected
      through the analysis of UPDRS, B'DS, BDI and PDQ-39 scores. The analysis of
      cardiorespiratory parameters showed significant interaction effects between group
      and time for the Double Productpeak (time x group effect: F: 7.7 P=0.0003), the
      VO(2peak) (time x group effect: F: 4.8 P=0.007), and the VO(2)/kg ratio (time x
      group effect: F: 4.3 P=0.009), owing to their decrease after aerobic training to
      an extent that was never observed after Qigong treatment. CONCLUSIONS: Aerobic
      training exerts a significant impact on the ability of moderately disabled PD
      patients to cope with exercise, although it does not improve their self
      sufficiency and quality of life.

PMID- 17039222
TI  - Constraint-induced movement therapy: an original concept in rehabilitation.

PMID- 17039223
TI  - The learned nonuse phenomenon: implications for rehabilitation.
AB  - Research on monkeys with a single forelimb from which sensation is surgically
      abolished demonstrates that such animals do not use their deafferented limb even
      though they possess sufficient motor innervation to do so, a phenomenon labeled
      learned nonuse. This dissociation also occurs after neurological injury in
      humans. Instruments that measure these two aspects of motor function are
      discussed. The effects of a neurological injury may differ widely in regard to
      motor ability assessed on a laboratory performance test in which movements are
      requested and actual spontaneous use of an extremity in real-world settings,
      indicating that these parameters need to be evaluated separately. The methods
      used in Constraint-Induced Movement therapy (CI therapy) research to
      independently assess these two domains are reliable and valid. We suggest that
      these tests have applicability beyond studies involving CI therapy for stroke and
      may be of value for determining motor status in other types of motor disorders
      and with other types of treatment. The learned nonuse formulation also predicts
      that a rehabilitation treatment may have differential effects on motor
      performance made on request and actual spontaneous amount of use of a more
      affected upper extremity in the life situation. CI therapy produces improvements
      in the former, but focuses attention on the latter and, in fact, spontaneous use
      of the limb is where this intervention has by far its greatest effect. The
      evidence suggests that this result is driven by use of a ''transfer package'' of
      techniques, which can be used with other therapies to increase the transfer of
      improvements made in the clinic to the life situation. The use of CI therapy in
      humans began with the upper extremity after stroke and was then extended for the
      upper extremity to cerebral palsy in young children (8 months to 8 years old) and
      traumatic brain injury. A form of CI therapy was developed for the lower
      extremities and was used effectively after stroke, spinal cord injury, and
      fractured hip. Adaptations of CI therapy have also been developed for aphasia (CI
      aphasia therapy), focal hand dystonia in musicians and phantom limb pain. The
      range of these applications suggests that CI therapy is not only a treatment for
      stroke, for which it is most commonly used, but for learned nonuse in general,
      which manifests as excess motor disability in a number of conditions which until
      now have been refractory to treatment.

PMID- 17039224
TI  - Constraint-induced movement therapy: characterizing the intervention protocol.
AB  - Constraint-induced movement therapy (CI therapy) is a rehabilitation treatment
      approach that improves more-affected extremity use following a stroke, especially
      in the life situation. The originators of the approach describe CI therapy as
      consisting of a family of therapies including a number of treatment components
      and subcomponents. When thinking of CI therapy, rehabilitation researchers and
      clinicians frequently cite a restraining mitt on the less affected arm as the
      main active ingredient behind improvements in motor function. However,
      substantial data suggest that restraint makes actually a relatively small
      contribution to treatment outcome. This paper provides a detailed description of
      the multiple treatment elements included in the CI therapy protocol as used in
      our research laboratory. Our aim is to improve understanding of CI therapy and
      the research supporting its use.

PMID- 17039225
TI  - Neuroplasticity and constraint-induced movement therapy.
AB  - Recent years have seen a proliferation of animal and human studies that have
      associated significant changes in regional brain physiology with sustained
      altered environmental or somatic stimuli. The behavioral consequences in such
      instances can be adaptive or maladaptive. As would be expected, constraint
      induced movement therapy (CI therapy), which has been found to be beneficial for
      chronic stroke hemiparesis, has been repeatedly associated with significant
      plastic brain changes in a variety of studies that have included transcranial
      magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), or
      other approaches. In some instances, the initial degree of brain reorganization
      occurred in parallel with the improvement in spontaneous, real-world use by the
      more-affected hand, which suggests that plastic brain changes in some manner
      support therapeutic effects. However, the studies are also inconsistent with
      respect to whether the reorganization changes occur more in the lesioned vs
      unlesioned hemisphere. Interpreting the physiological outcomes post-treatment is
      compromised by inconsistencies in study design in the nature of treatment
      administered, participant recruitment, imaging modality, and extent of follow-up.
      Improved understanding of the biological basis for neuroplasticity in CI therapy
      may be obtained through rigorous control of study approaches and through
      evaluating treatment changes with more than one modality in the same patients
      concurrently. New quantitative structural brain imaging techniques may allow
      measuring morphological changes following CI therapy to test hypotheses of
      regional brain recruitment in use-dependent therapy while avoiding the
      variability of functional imaging and mapping techniques and the difficulties and
      assumptions imposed by requiring active limb movement during scanning.

PMID- 17039226
TI  - Diffuse large B-cell lymphoma: a heterogeneous group of non-Hodgkin lymphomas
      comprising several distinct clinicopathological entities.
AB  - Diffuse large B-cell lymphoma (DLBCL) as defined by the World Health Organization
      (WHO) classification is clinically, morphologically and genetically a
      heterogeneous group of malignant proliferations of large lymphoid B cells. Over
      the last 6 years, several studies have been published improving our understanding
      of these lymphomas. These studies analyzed DLBCL by their gene expression
      profile, provided further information on some of the variants of DLBCL listed in
      the WHO classification and stressed the impact of the site of origin of these
      tumors. This review summarizes these recent data and explores their impact on the
      recognition of new clinicopathological lymphoma entities.

PMID- 17039227
TI  - Perforin A91V polymorphism and putative susceptibility to hematological
      malignancies.

PMID- 17039229
TI  - Transfusions after nonmyeloablative or reduced-intensity conditioning regimens.

PMID- 17039228
TI  - Homing, proliferation and survival sites of human leukemia cells in vivo in
      immunodeficient mice.
AB  - The cellular components of the hematopoietic stem cell niche have been gradually
      identified. However, the niche for malignant hematopoiesis remains to be
      elucidated. Here, using human leukemia cells, which could be transplanted to
      immunodeficient mice, we studied the in vivo homing, proliferation and survival
      sites by immunohistopathology, compared with the corresponding sites for cord
      blood CD34(+) (CBCD34(+)) cells. The human leukemia cells initially localized on
      the surface of osteoblasts in the epiphysial region, and expanded to the inner
      vascular and diaphysial regions within 4 weeks. The percentage of CD34(+)
      leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5
      bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active
      site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern
      of homing and proliferation to leukemia cells. After high-dose administration of
      cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in
      the perivascular endothelium as well as in contact with the trabecular endosteum.
      These findings suggest that xenotransplantation into immunodeficient mice
      provides a useful model to study the leukemia niche.

PMID- 17039230
TI  - Eradication of JAK2 V617F mutation after allogeneic transplantation in a patient
      with myelofibrosis with myeloid metaplasia.

PMID- 17039231
TI  - Molecular pathways in follicular lymphoma.
AB  - Follicular lymphoma (FL) is one of the most common B-cell non-Hodgkin's
      lymphomas. The initiating genetic event found in approximately 90% of FL is the
      t(14;18), causing constitutive expression of the antiapoptotic BCL-2 protein. The
      exact secondary alterations leading to full FL development are still poorly
      defined. In this review, we address (i) the genetic pathways associated with
      tumorigenesis and progression of FL, (ii) the role of micro-environmental factors
      with emphasis on B-cell receptor ligands and (iii) lymphoma models in mice and
      what they teach us about lymphomagenesis in man.

PMID- 17039232
TI  - The downregulation of asparagine synthetase expression can increase the
      sensitivity of cells resistant to l-asparaginase.

PMID- 17039233
TI  - Antibody-mediated targeting of viral vectors to the Fc receptor expressed on
      acute myeloid leukemia cells.

PMID- 17039235
TI  - The CCR4 as a novel-specific molecular target for immunotherapy in Hodgkin
      lymphoma.
AB  - Here, we report that tumor cells from some patients (23.8%) with Hodgkin lymphoma
      (HL) are positive for CC chemokine receptor 4 (CCR4). We therefore tested the
      chimeric anti-CCR4 monoclonal antibody (mAb), KM2760, the Fc region of which is
      defucosylated to enhance antibody-dependent cellular cytotoxicity (ADCC), as a
      novel immunotherapy for refractory HL. KM2760 demonstrated a promising antitumor
      activity in the CCR4-positive HL-bearing mouse model in the therapeutic setting.
      Although KM2760 did not induce any ADCC mediated by mouse natural killer (NK)
      cells, it significantly enhanced phagocytosis mediated by mouse
      monocytes/macrophages against the CCR4-positive HL cell line in vitro. Together
      with the findings that KM2760 did not exhibit any complement-dependent
      cytotoxicity or direct antiproliferation activity in vitro, these data indicated
      that KM2760 exerted its robust in vivo antitumor activity via
      monocytes/macrophages in mice. In the human system, KM2760 enhanced phagocytic
      activity mediated by monocytes/macrophages. Furthermore, it induced robust ADCC
      mediated by NK cells against the CCR4-positive HL cell line in vitro. Thus, it is
      conceivable that KM2760 would have much more potent antitumor activity in humans
      than in mice. Collectively, this study strongly indicates that anti-CCR4 mAb
      could be a novel treatment modality for patients with CCR4-positive HL.

PMID- 17039234
TI  - Allogeneic stem cell transplantation improves the outcome of adults with
      t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic
      leukemia: results of the prospective multicenter LALA-94 study.
AB  - Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or
      t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an
      intensified post-remission therapy using a high-dose chemotherapy course followed
      by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A
      PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA
      94 multicenter prospective study. Patients in the MLL group had higher WBC counts
      and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to
      other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a
      donor were assigned to alloSCT (n=22), the remaining patients with were
      randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall
      survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS
      was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The
      results of this study show that chemotherapy intensification did not overcome the
      poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be
      offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New
      therapeutic approaches are needed for patients without donor.

PMID- 17039236
TI  - Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying
      the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de
      Cytogenetique Hematologique.
AB  - Recently, we and others described a new chromosomal rearrangement, that is,
      inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta)
      (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic
      leukemia (T-ALL) patients leading to transcriptional activation of especially
      HOXA10. To further address the clinical, immunophenotypical and molecular genetic
      findings of this chromosomal aberration, we studied 330 additional T-ALLs. This
      revealed TCRbeta-HOXA rearrangements in five additional patients, which brings
      the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis
      for HOXA10 gene expression was performed in 170 T-ALL patients and detected
      HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta
      HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10
      transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged
      cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta
      HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations
      frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were
      not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and
      NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In
      conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct
      cytogenetic subgroup by clinical, immunophenotypical and molecular genetic
      characteristics.

PMID- 17039237
TI  - Prospective multicentric molecular study for poor prognosis fusion transcripts at
      diagnosis in adult B-lineage ALL patients: the LALA 94 experience.

PMID- 17039238
TI  - Gene expression profiles of AML derived stem cells; similarity to hematopoietic
      stem cells.
AB  - Tumors contain a fraction of cancer stem cells that maintain the propagation of
      the disease. The CD34(+)CD38(-) cells, isolated from acute myeloid leukemia
      (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the
      CD34(+)CD38(-) cell fraction from AML and compared their gene expression profiles
      to the CD34(+)CD38(+) cell fraction, using microarrays. We found 409 genes that
      were at least twofold over- or underexpressed between the two cell populations.
      These include underexpression of DNA repair, signal transduction and cell cycle
      genes, consistent with the relative quiescence of stem cells, and chromosomal
      aberrations and mutations of leukemic cells. Comparison of the LSC expression
      data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the
      modulated genes are shared by both LSC and HSC, supporting the suggestion that
      the LSC originated within the HSC progenitors. We focused on the Notch pathway
      since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples.
      We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved
      in Jagged and Notch signaling, inhibits LSC growth in colony formation assays.
      Identification of additional genes that regulate LSC self-renewal may provide new
      targets for therapy.

PMID- 17039239
TI  - Stimulation of purinergic receptors modulates chemokine expression in human
      keratinocytes.
AB  - ATP is abundantly released from stressed or damaged cells in response to
      mechanical stimulation, bacteria, or noxious agents. In this study, we have
      investigated the possible involvement of P2 receptors (receptor for extracellular
      nucleotides) in the expression and release of inflammatory mediators by human
      keratinocytes. Notably, extracellular ATP displayed a complex regulation of IFN
      gamma-stimulated chemokine expression, with upregulation of CC chemokine ligand 2
      (CCL2), CCL5 and CXC chemokine ligand 8 (CXCL8), and suppression of the receptor
      CXC chemokine receptor 3 (CXCR3), CXCL9, CXCL10, and CXCL11. The effect of ATP
      was mimicked by ADP and adenosine-5'-O-3-thiotriphosphate, whereas 2',3'-O-(4
      benzoylbenzoyl) ATP (BzATP) downmodulated all chemokines investigated. UTP had no
      effect on IFN-gamma-stimulated chemokine secretion. The broad-spectrum P2
      receptor antagonist suramin and the selective P2Y1 inhibitor adenosine 3'
      phosphate 5'-phosphosulfate counteracted the effect of ATP on secretion of all
      the chemokines examined, whereas pyridoxal phosphate 6-azophenyl 2',4'-disulfonic
      acid and KN62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl] 4
      phenylpiperazine) partially prevented the inhibitory effect of ATP on CXCL10
      secretion, but on the other hand potentiated the ATP-stimulatory effect on CCL5,
      CCL2, and CXCL8 release. In lesional skin of psoriasis and atopic dermatitis
      patients, intense P2X7 reactivity was confined to the cell membrane of the basal
      layer, whereas diffuse P2Y1 immunostaining was found throughout the epidermis.
      Collectively, our data suggest that the orchestrated activation of distinct P2Y
      and P2X receptors modulates skin inflammation.

PMID- 17039240
TI  - Regulation of NF-kappaB activity and keratinocyte differentiation by the RIP4
      protein: implications for cutaneous wound repair.
AB  - Receptor-interacting proteins (RIPs) are important regulators of cell
      proliferation and differentiation. As RIP4 is a crucial modulator of epidermal
      differentiation, we analyzed the expression of different rip genes in healing
      skin wounds. Rip4 expression was strongly downregulated in keratinocytes of the
      hyperproliferative epithelium at the wound edge early after injury and only
      returned to basal levels after completion of wound repair. Rip3 expression was
      strongly induced as early as 1 day after wounding. In contrast, rip and rip2
      expression remained unaltered. To determine the factors that regulate rip4 gene
      expression in keratinocytes, human HaCaT keratinocytes were used as a model
      system. We found that scratch wounding as well as treatment with whole serum,
      phorbol esters, the growth/differentiation factors epidermal growth factor,
      transforming growth factor-beta, and activin A, or the proinflammatory cytokines
      tumor necrosis factor-alpha and IL-1beta strongly suppressed rip4 expression in
      these cells. In contrast, the steroid dexamethasone and all-trans retinoic acid
      slightly stimulated rip4 expression. Suppression of rip4 expression in
      keratinocytes using small interfering RNA technology reduced the activation of NF
      kappaB, and enhanced the expression of epidermal differentiation markers in these
      cells. These data suggest important and unique functions of different RIP
      proteins in keratinocytes of normal and wounded skin.

PMID- 17039241
TI  - Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host
      disease express a constitutive antiapoptotic phenotype.
AB  - The normal gene expression profile of rete-tip keratinocytes targeted in human
      graft-versus-host disease (GVHD) remains unexplored. Murine lingual epithelium,
      unlike murine skin, consists of a basal layer that resembles human cutaneous rete
      ridges and harbors rete tip-associated cells that express cytokeratin 15 (K15), a
      marker for epithelial stem cells. Target cell apoptosis in murine GVHD
      preferentially involves subpopulations of basal cells that (1) reside at tips of
      lingual rete ridge-like prominences (RLPs), (2) constitutively express K15
      protein, (3) express the proapoptotic protein Bax early in disease progression,
      and (4) coincide spatially with putative epithelial stem cells. Here, we show by
      real-time reverse transcription-PCR that immunohistochemistry-guided laser
      captured K15-positive (K15+) murine basal cells constitutively express
      quantitatively higher mRNA levels for K15 but lower mRNA levels of Bax than do
      K15- basal cells, consistent with the presumed stem cell nature of K15+ basal
      cells. Moreover, apoptosis gene array screening of K15+ microdissected basal
      cells demonstrated a dominant trend toward the preferential expression of genes
      associated with protection from apoptosis. Accordingly, genes that regulate
      apoptotic vulnerability are differentially expressed in basal layer
      subpopulations distinguishable by K15 expression.

PMID- 17039242
TI  - Altered penetration of polyethylene glycols into uninvolved skin of atopic
      dermatitis patients.
AB  - Involved regions of the skin in atopic dermatitis (AD) patients have an altered
      barrier function. Whether uninvolved skin also has a diminished barrier is
      controversial. To assess the barrier function of uninvolved skin in AD patients,
      the percutaneous penetration of polyethylene glycols (PEGs) of various molecular
      sizes was determined in vivo in AD patients and control subjects using tape
      stripping of the stratum corneum (SC). The diffusion and partition coefficients
      were determined using Fick's second law of diffusion. The SC thickness was
      similar in both groups; however, the trans-epidermal water loss was higher in
      atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was
      twice as high as through normal skin, and decreased with increasing molecular
      weight (MW) in both groups. The partition coefficient in the skin of AD patients
      was half of that for normal skin but as for normal skin, there was no MW
      dependency. Although atopic skin exhibited altered barrier with respect to
      diffusion and partitioning, the permeability coefficients were nearly the same
      for atopic and normal skin. The results support the assumption of altered skin
      barrier of AD patients even in the skin that is visibly unaffected by disease.

PMID- 17039243
TI  - Tissue homing and persistence of defined antigen-specific CD8+ tumor-reactive T
      cell clones in long-term melanoma survivors.
AB  - Tumor antigen-specific cytotoxic T cells (CTLs) play a major role in the adaptive
      immune response to cancers. This CTL response is often insufficient because of
      functional impairment, tumor escape mechanisms, or inhibitory tumor
      microenvironment. However, little is known about the fate of given tumor-specific
      CTL clones in cancer patients. Studies in patients with favorable outcomes may be
      very informative. In this longitudinal study, we tracked, quantified, and
      characterized functionally defined antigen-specific T-cell clones ex vivo, in
      peripheral blood and at tumor sites, in two long-term melanoma survivors. MAGE
      A10-specific CD8+ T-cell clones with high avidity to antigenic peptide and tumor
      lytic capabilities persisted in peripheral blood over more than 10 years, with
      quantitative variations correlating with the clinical course. These clones were
      also found in emerging metastases, and, in one patient, circulating clonal T
      cells displayed a fully differentiated effector phenotype at the time of relapse.
      Longevity, tumor homing, differentiation phenotype, and quantitative adaptation
      to the disease phases suggest the contribution of the tracked tumor-reactive
      clones in the tumor control of these long-term metastatic survivor patients.
      Focusing research on patients with favorable outcomes may help to identify
      parameters that are crucial for an efficient antitumor response and to optimize
      cancer immunotherapy.

PMID- 17039244
TI  - Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin
      mutations.
AB  - Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by
      mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of
      basal keratinocytes leading to epidermal cytolysis and blistering. Patients
      present with widely varying severity and are classified in three main subtypes:
      EBS Weber-Cockayne (EBS-WC), EBS Kobner (EBS-K), and EBS Dowling-Meara (EBS-DM),
      based on distribution and pattern of blisters. We could identify K5/K14 mutations
      in 20 out of the 43 families registered as affected by dominant EBS in Scotland;
      with previous studies this covers 70% of all Scottish EBS patients, making this
      the most comprehensively analyzed EBS population. Nine mutations are novel. All
      mutations lie within five previously identified rod domain hotspots and the
      severest blistering was associated with mutations in the helix boundary motifs.
      In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both
      within and between families, suggesting a contribution of additional factors to
      the phenotype. In some patients, no mutations were found in K5, K14, or K15,
      suggesting involvement of other genes. The results confirm that EBS is best
      considered as a single disorder with a spectrum of phenotypic variations, from
      severe EBS-DM at one extreme to mild EBS-WC at the other.

PMID- 17039245
TI  - Optimized methodology for sequential extraction of RNA and protein from small
      human skin biopsies.
AB  - Current translational human studies are moving in the direction of concurrent
      genomic and proteomic analysis using small clinical samples. Skin tissue,
      although easily accessible, is difficult to process owing to its natural
      resistance to mechanical shearing and high levels of RNases and proteases.
      Currently, these complications result in degraded RNA samples with variable
      yield. We have developed a method of sequential extraction of high quality RNA
      and protein from a single 3 mm full thickness skin punch biopsy. This method
      yields 1-2 microg of RNA and 150 microg of protein, which is usable in many
      sensitive downstream applications including microarray, quantitative real-time
      PCR, two-dimensional gel electrophoresis and Western blot analysis.

PMID- 17039246
TI  - The mitochondrial DNA common deletion is present in most basal and squamous cell
      carcinoma samples isolated by laser capture microdissection but generally at
      reduced rather than increased levels.

PMID- 17039247
TI  - Apoptosis and caspases regulate death and inflammation in sepsis.
AB  - Although the prevailing concept has been that mortality in sepsis results from an
      unbridled hyper-inflammatory cytokine-mediated response, the failure of more than
      30 clinical trials to treat sepsis by controlling this cytokine response requires
      a 'rethink' of the molecular mechanism underpinning the development of sepsis. As
      we discuss here, remarkable new studies indicate that most deaths from sepsis are
      actually the result of a substantially impaired immune response that is due to
      extensive death of immune effector cells. Rectification of this apoptotic
      inflammatory imbalance using modulators of caspases and other components of the
      cell-death pathway have shown striking efficacy in stringent animal models of
      sepsis, indicating an entirely novel path forward for the clinical treatment of
      human sepsis.

PMID- 17039248
TI  - Apoptosis-inducing factor is a major contributor to neuronal loss induced by
      neonatal cerebral hypoxia-ischemia.
AB  - Nine-day-old harlequin (Hq) mice carrying the hypomorphic apoptosis-inducing
      factor (AIF)(Hq) mutation expressed 60% less AIF, 18% less respiratory chain
      complex I and 30% less catalase than their wild-type (Wt) littermates. Compared
      with Wt, the infarct volume after hypoxia-ischemia (HI) was reduced by 53 and 43%
      in male (YX(Hq)) and female (X(Hq)X(Hq)) mice, respectively (P<0.001). The Hq
      mutation did not inhibit HI-induced mitochondrial release of cytochrome c or
      activation of calpain and caspase-3. The broad-spectrum caspase inhibitor
      quinoline-Val-Asp(OMe)-CH(2)-PH (Q-VD-OPh) decreased the activation of all
      detectable caspases after HI, both in Wt and Hq mice. Q-VD-OPh reduced the
      infarct volume equally in Hq and in Wt mice, and the combination of Hq mutation
      and Q-VD-OPh treatment showed an additive neuroprotective effect. Oxidative
      stress leading to nitrosylation and lipid peroxidation was more pronounced in
      ischemic brain areas from Hq than Wt mice. The antioxidant edaravone decreased
      oxidative stress in damaged brains, more pronounced in the Hq mice, and further
      reduced brain injury in Hq but not in Wt mice. Thus, two distinct strategies can
      enhance the neuroprotection conferred by the Hq mutation, antioxidants,
      presumably compensating for a defect in AIF-dependent redox detoxification, and
      caspase inhibitors, presumably interrupting a parallel pathway leading to
      cellular demise.

PMID- 17039249
TI  - Genetic variance modifies apoptosis susceptibility in mature oocytes via
      alterations in DNA repair capacity and mitochondrial ultrastructure.
AB  - Although the identification of specific genes that regulate apoptosis has been a
      topic of intense study, little is known of the role that background genetic
      variance plays in modulating cell death. Using germ cells from inbred mouse
      strains, we found that apoptosis in mature (metaphase II) oocytes is affected by
      genetic background through at least two different mechanisms. The first,
      manifested in AKR/J mice, results in genomic instability. This is reflected by
      numerous DNA double-strand breaks in freshly isolated oocytes, causing a high
      apoptosis susceptibility and impaired embryonic development following
      fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis
      and improves embryonic development. The second, manifested in FVB mice, results
      in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with
      cytochrome c release and a high apoptosis susceptibility, the latter of which is
      suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of
      'normal' mitochondria. Therefore, background genetic variance can profoundly
      affect apoptosis in female germ cells by disrupting both genomic DNA and
      mitochondrial integrity.

PMID- 17039250
TI  - Mitochondrial membrane remodeling in apoptosis: an inside story.

PMID- 17039251
TI  - RNA interference-inducing hairpin RNAs in plants act through the viral defence
      pathway.
AB  - RNA interference (RNAi) is widely used to silence genes in plants and animals. It
      operates through the degradation of target mRNA by endonuclease complexes guided
      by approximately 21 nucleotide (nt) short interfering RNAs (siRNAs). A similar
      process regulates the expression of some developmental genes through
      approximately 21 nt microRNAs. Plants have four types of Dicer-like (DCL) enzyme,
      each producing small RNAs with different functions. Here, we show that DCL2, DCL3
      and DCL4 in Arabidopsis process both replicating viral RNAs and RNAi-inducing
      hairpin RNAs (hpRNAs) into 22-, 24- and 21 nt siRNAs, respectively, and that loss
      of both DCL2 and DCL4 activities is required to negate RNAi and to release the
      plant's repression of viral replication. We also show that hpRNAs, similar to
      viral infection, can engender long-distance silencing signals and that hpRNA
      induced silencing is suppressed by the expression of a virus-derived suppressor
      protein. These findings indicate that hpRNA-mediated RNAi in plants operates
      through the viral defence pathway.

PMID- 17039252
TI  - DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent
      on Cdt2 and Ddb1.
AB  - Cdt1 is an essential protein required for licensing of replication origins. Here,
      we show that in Schizosaccharomyces pombe, Cdt1 is proteolysed in M and G1 phases
      in response to DNA damage and that this mechanism seems to be conserved from
      yeast to Metazoa. This degradation does not require Rad3 and Cds1, indicating
      that it is independent of classic DNA damage and replication checkpoint pathways.
      Damage-induced degradation of Cdt1 is dependent on Cdt2 and Ddb1, which are
      components of a Cul4 ubiquitin ligase. We also show that Cdt2 and Ddb1 are needed
      for cell-cycle changes in Cdt1 levels in the absence of DNA damage. Cdt2 and Ddb1
      have been shown to be involved in the degradation of the Spd1 inhibitor of
      ribonucleotide reductase after DNA damage, and we speculate that Cdt1
      downregulation might contribute to genome stability by reducing demand on dNTP
      pools during DNA repair.

PMID- 17039253
TI  - The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic
      lateral sclerosis model.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by motor neuron loss and muscle wasting. In muscles of ALS patients, Nogo-A-a
      protein known to inhibit axon regeneration-is ectopically expressed at levels
      that correlate with the severity of the clinical symptoms. We now show that the
      genetic ablation of Nogo-A extends survival and reduces muscle denervation in a
      mouse model of ALS. In turn, overexpression of Nogo-A in wild-type muscle fibres
      leads to shrinkage of the postsynapse and retraction of the presynaptic motor
      ending. This suggests that the expression of Nogo-A occurring early in ALS
      skeletal muscle could cause repulsion and destabilization of the motor nerve
      terminals, and subsequent dying back of the axons and motor neurons.

PMID- 17039254
TI  - Ca2+ lightning conveys cell-cell contact information inside the cells.
AB  - Cells communicate with each other to form organized structures by cell-cell
      adhesion and cell-cell repulsion, but it remains to be clarified how cell-cell
      contact information is converted into intracellular signals. Here, we show that
      cells in contact with neighbouring cells generate local transient intracellular
      Ca(2+) signals (Ca(2+) lightning). Ca(2+) lightning was observed near cell-cell
      contact regions and was not observed in the central regions of cells or in
      solitary cells that were not in contact with other cells. We also show that
      Ca(2+) lightning is able to regulate cell-cell repulsion by means of PYK2, a
      Ca(2+)-activated protein tyrosine kinase, which induces focal adhesion
      disassembly in a Ca(2+)-dependent manner. These results show that cell-cell
      contact information might be transmitted by Ca(2+) lightning to regulate
      intracellular events.

PMID- 17039256
TI  - Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta receptor
      inhibits mitotic progression.
AB  - Overexpression of pituitary tumor-transforming 1 (PTTG1) is associated with
      thyroid cancer. We found elevated PTTG1 levels in the thyroid tumors of a mouse
      model of follicular thyroid carcinoma (TRbeta(PV/PV) mice). Here we examined the
      molecular mechanisms underlying elevated PTTG1 levels and the contribution of
      increased PTTG1 to thyroid carcinogenesis. We showed that PTTG1 was physically
      associated with thyroid hormone beta receptor (TRbeta) as well as its mutant,
      designated PV. Concomitant with thyroid hormone-induced (T3-induced) degradation
      of TRbeta, PTTG1 proteins were degraded by the proteasomal machinery, but no such
      degradation occurred when PTTG1 was associated with PV. The degradation of
      PTTG1/TRbeta was activated by the direct interaction of the liganded TRbeta with
      steroid receptor coactivator 3 (SRC-3), which recruits proteasome activator
      PA28gamma. PV, which does not bind T3, could not interact directly with SRC
      3/PA28gamma to activate proteasome degradation, resulting in elevated PTTG1
      levels. The accumulated PTTG1 impeded mitotic progression in cells expressing PV.
      Our results unveil what we believe to be a novel mechanism by which PTTG1, an
      oncogene, is regulated by the liganded TRbeta. The loss of this regulatory
      function in PV led to an aberrant accumulation of PTTG1 disrupting mitotic
      progression that could contribute to thyroid carcinogenesis.

PMID- 17039255
TI  - Virus-induced type I IFN stimulates generation of immunoproteasomes at the site
      of infection.
AB  - IFN-gamma is known as the initial and primary inducer of immunoproteasomes during
      viral infections. We now report that type I IFN induced the transcription and
      translation of immunoproteasome subunits, their incorporation into the proteasome
      complex, and the generation of an immunoproteasome-dependent CD8 T cell epitope
      in vitro and provide in vivo evidence that this mechanism occurs prior to IFN
      gamma responses at the site of viral infection. Type I IFN-mediated generation of
      immunoproteasomes was initiated by either poly(I:C) or HCV RNA in human hepatoma
      cells and was inhibited by neutralization of type I IFN. In serial liver biopsies
      of chimpanzees with acute HCV infection, increases in immunoproteasome subunit
      mRNA preceded intrahepatic IFN-gamma responses by several weeks, instead
      coinciding with intrahepatic type I IFN responses. Thus, viral RNA-induced innate
      immune responses regulate the antigen-processing machinery, which occurs prior to
      the detection of IFN-gamma at the site of infection. This mechanism may
      contribute to the high effectiveness (95%) of type I IFN-based therapies if
      administered early during HCV infection.

PMID- 17039257
TI  - Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition.
AB  - Caveolin-3, the muscle-specific isoform of caveolins, plays important roles in
      signal transduction. Dominant-negative mutations of the caveolin-3 gene cause
      autosomal dominant limb-girdle muscular dystrophy 1C (LGMD1C) with loss of
      caveolin-3. However, identification of the precise molecular mechanism leading to
      muscular atrophy in caveolin-3-deficient muscle has remained elusive. Myostatin,
      a member of the muscle-specific TGF-beta superfamily, negatively regulates
      skeletal muscle volume. Here we report that caveolin-3 inhibited myostatin
      signaling by suppressing activation of its type I receptor; this was followed by
      hypophosphorylation of an intracellular effector, Mad homolog 2 (Smad2), and
      decreased downstream transcriptional activity. Loss of caveolin-3 in P104L mutant
      caveolin-3 transgenic mice caused muscular atrophy with increase in
      phosphorylated Smad2 (p-Smad2) as well as p21 (also known as Cdkn1a), a myostatin
      target gene. Introduction of the myostatin prodomain, an inhibitor of myostatin,
      by genetic crossing or intraperitoneal administration of the soluble type II
      myostatin receptor, another inhibitor, ameliorated muscular atrophy of the mutant
      caveolin-3 transgenic mice with suppression of p-Smad2 and p21 levels. These
      findings suggest that caveolin-3 normally suppresses the myostatin-mediated
      signal, thereby preventing muscular atrophy, and that hyperactivation of
      myostatin signaling participates in the pathogenesis of muscular atrophy in a
      mouse model of LGMD1C. Myostatin inhibition may be a promising therapy for LGMD1C
      patients.

PMID- 17039259
TI  - Arterial infections in the new millenium: an old problem revisited.
AB  - The natural history of infected aneurysms or arterial infections is characterized
      by rapid expansion leading to rupture, pseudoaneurysm formation, and sepsis.
      Treatment options include in situ grafting either with prosthetic or autogenous
      grafts or with cryopreserved allografts (CPAs), resection of the aneurysm with
      remote bypass grafting, and ligation. The purpose of this study was to review our
      recent experience with these infections and to present long-term follow-up with
      in situ CPAs. From January 2000 through June 2005, we treated nine patients with
      infected aneurysms and one patient with an infection without aneurysm formation.
      The infection involved the infrarenal abdominal aorta in six patients and the
      femoral artery in three patients. One patient had an infected splenic artery
      aneurysm. Aortic rupture occurred in five of the six patients with infected
      aortas. Two of the three patients with infected femoral aneurysms presented with
      recurrent hemorrhage. Of the six patients with aortic infections, five were
      treated with in situ CPAs. One patient was treated with aortic resection and
      axillofemoral grafting. Two patients with femoral aneurysms were treated with in
      situ CPAs, and the third patient underwent aneurysm resection and prosthetic
      grafting through the obturator foramen. The patient with the splenic aneurysm
      underwent combined valve replacement, aneurysm resection, and splenectomy. Three
      of the six patients with aortic infections died postoperatively, all of whom were
      septic at presentation. The cause of death in these three patients was multiple
      organ failure in two and overwhelming sepsis in one. The three survivors are
      alive and well with up to 5-year follow-up. The three patients with infected
      femoral aneurysms are alive and well with follow-up extending to 44 months. The
      patient with the splenic aneurysm is doing well. No recurrent infections have
      been noted among the survivors. The CPAs have remained structurally intact in
      all. The mortality rate among patients with abdominal aortic infections remains
      high and is likely related to their preoperative septic state. In situ grafting
      with CPAs appears to be a reasonable treatment option for arterial infections.
      CPAs appear to maintain their structural integrity and to be resistant to
      recurrent infection.

PMID- 17039258
TI  - NF-kappaB2 is required for the establishment of central tolerance through an Aire
      dependent pathway.
AB  - NF-kappaB2-deficient mice have impaired T and B cell responses. We found,
      however, that in these mice there was severe infiltration of lymphocytes into
      multiple organs and increased activity of autoantibodies to peripheral tissue
      antigens in a manner similar to that of autoimmune regulator-deficient (Aire
      deficient) mice. We further demonstrated that NF-kappaB2 was required for thymic
      Aire gene transcriptional regulation. The Nfkb2(-/-) thymus had distinct cortical
      and medullar structures, but reduced Aire and target gene expression of
      peripheral tissue antigens. Engraftment of Nfkb2(-/-) thymic stroma to nude mice
      recapitulated the autoimmune phenotype of the native Nfkb2(-/-) mice, confirming
      a key defect in central tolerance. Lymphotoxin beta receptor (LTbetaR) ligation
      induced Aire gene expression was also largely abolished in the absence of NF
      kappaB2. Thus NF-kappaB2 downstream of LTbetaR plays an important role in the
      regulation of central tolerance in an Aire-dependent manner.

PMID- 17039260
TI  - SAA1 alpha/alpha alleles in Behcet's disease related amyloidosis.
AB  - Behcet's disease (BD) related amyloidosis is relatively rare. Serum amyloid A
      protein (SAA) protein gene polymorphism is one of the factors implicated in the
      pathogenesis of AA type amyloidosis. The aim of this study is to investigate SAA1
      gene polymorphism in different patient groups: (1) BD related amyloidosis, (2) BD
      without amyloidosis, and (3) healthy controls. One hundred eleven patients from
      three main groups were included in the study: (1) BD related amyloidosis (n = 9),
      (2) BD without amyloidosis (n = 39), and (3) healthy controls (n = 63).
      Homozygous alpha/alpha is present in 78% of patients with BD and amyloidosis. The
      SAA1 alpha/alpha genotype is significantly more common among patients with BD and
      amyloidosis. This study demonstrated increased frequency of alpha/alpha genotype
      in BD related amyloidosis. To our knowledge, the relationship between alpha/alpha
      genotype and BD related amyloidosis was not studied previously. In conclusion,
      the SAA1 alpha/alpha genotype is a risk factor for amyloidosis in BD.

PMID- 17039261
TI  - Successful treatment of life-threatening intestinal ulcer in Behcet's disease
      with infliximab: rapid healing of Behcet's ulcer with infliximab.
AB  - Behcet's disease is a chronic, relapsing, multisystem inflammatory disorder
      characterized predominantly by recurrent orogenital ulcers, skin involvement, and
      uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases,
      but ocular, gastrointestinal, and central nervous system involvement may occur in
      severe cases. We report in this study the successful treatment with infliximab of
      severe life-threatening GI bleeding caused by an ileal ulcer in a patient with
      Behcet's disease. Antitumor necrosis factor (TNF) therapy could be an emergency
      therapeutic option in patients with massively bleeding Behcet's disease and
      unstable patients or those with acute bleeding with other TNF-alpha-mediated
      autoimmune diseases. Another option for anti-TNF therapy could be as bridging
      management between conservative and surgical treatment.

PMID- 17039262
TI  - Laser speckle imaging of dynamic changes in flow during photodynamic therapy.
AB  - We present a study investigating the use of laser speckle imaging (LSI) for
      monitoring blood flow during photodynamic therapy (PDT) utilizing the therapeutic
      illumination radiation. The coherent nature of a laser source, often used in PDT,
      offers the possibility of obtaining information on the blood flow without
      interrupting treatment. We have found that in the rat skin-fold observation
      chamber, it is possible to monitor the vasculature response to PDT in individual
      arteries, veins and in tumour microvasculature with significantly higher spatial
      and temporal resolution than current methods. This illustrates the potential for
      LSI for monitoring PDT, in particular for vascular-localizing photosensitizers,
      where current non-invasive methods are difficult because of high absorption due
      to blood and the specific localization of photosensitizer within the vasculature.
      However, critical problems need to be further investigated and solved, like the
      influence of tissue sampling volume, changing of optical properties and movement
      artefacts from other vessels on the LSI signal. Until then, the real potential of
      LSI for monitoring blood flow remains of limited value.

PMID- 17039263
TI  - Hormonal therapy for postmenopausal breast cancer: the science of sequencing.
AB  - Oestrogens play important roles in the natural history of breast cancer.
      Consequently, therapies have been developed to reduce oestrogen levels or to
      block signalling through oestrogen receptors (ER). These therapies include
      tamoxifen, selective oestrogen receptor modulators (SERMs), aromatase inhibitors
      (AIs) and selective oestrogen receptor downregulators (SERDs). All have proven
      clinical efficacy in postmenopausal women with ER-positive breast cancer and can
      be effective in the neoadjuvant and adjuvant settings, and in the management of
      advanced disease. This range of endocrine therapies offers the opportunity for
      prolonging benefit from treatment and delaying tumour recurrence/progression by
      combining the different classes of drugs or by using them sequentially.
      Evaluation of the potential clinical benefits of concomitant or sequential
      endocrine therapies should be based on considerations of efficacy and safety
      profiles, mechanisms of action/resistance and effects on tumour biology. Evidence
      from preclinical models and from randomized clinical trials in patients with
      postmenopausal breast cancer suggests that concomitant endocrine therapies are no
      more effective than AIs alone. However, using AIs either as initial therapy or
      sequentially after tamoxifen appears to produce more benefits beyond the use of
      tamoxifen alone.Currently, there are no proven algorithms for the planned,
      sequential use of the full range of endocrine therapies, particularly for the
      majority of patients who present with early breast cancer. Prospective,
      randomized clinical trials are needed to determine the best use of therapies in
      particular settings, taking into account the spectrum of molecular phenotypes in
      different tumours.

PMID- 17039264
TI  - Role of single nucleotide polymorphisms and haplotypes in BRCA1 in breast cancer:
      Czech case-control study.
AB  - We aimed at determining whether any association exists between six single
      nucleotide polymorphisms in breast cancer associated gene (BRCA1) and the risk of
      breast cancer. We constructed haplotypes and analyzed their importance as well.
      Clinico-pathological characteristics of breast cancer patients were included in
      the study to evaluate the prognostic impact of BRCA1 polymorphisms and
      haplotypes. Polymerase chain reaction-restriction fragment length polymorphism
      based genotyping assays were used to determine the frequency of polymorphisms in
      codons 356, 871, 1038, 1183, 1436, and 1613 of BRCA1 in a group of 306 incident
      breast cancer patients and 313 unaffected controls of Czech origin. Statistical
      analyses revealed that the BRCA1 Arg356 allele may play a protective role in
      breast cancer (age-adjusted OR = 0.61, CI = 0.39-0.94, p = 0.026). We also
      observed a significant correlation between polymorphism Gln356Arg and stage (p =
      0.026) in premenopausal cases suggesting that carriers of the wild Gln356Gln
      allele are at significantly higher risk of advanced disease. The most common
      haplotypes of BRCA1 did not play a significant role in breast cancer either as
      risk factors or as prognostic factors. The study on rare BRCA1 haplotypes however
      should be repeated using larger groups. In conclusion, the BRCA1-Gln356 allele
      presents risk factor in the onset and progression of breast cancer in Czech
      population and its use as a possible screening tool should be considered.

PMID- 17039265
TI  - Predicting response to primary chemotherapy: gene expression profiling of
      paraffin-embedded core biopsy tissue.
AB  - PURPOSE: Primary chemotherapy provides an ideal opportunity to correlate gene
      expression with response to treatment. We used paraffin-embedded core biopsies
      from a completed phase II trial to identify genes that correlate with response to
      primary chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage
      II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks
      x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned.
      Pretreatment core biopsy samples were interrogated for genes that might correlate
      with pathologic complete response (pCR). In addition to the individual genes, the
      correlation of the Oncotype DX Recurrence Score with pCR was examined. RESULTS:
      Of 70 patients enrolled in the parent trial, core biopsies samples with
      sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had
      inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two
      of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes
      correlating with pCR could be grouped into three large clusters: angiogenesis
      related genes, proliferation related genes, and invasion-related genes.
      Expression of estrogen receptor (ER)-related genes and Recurrence Score did not
      correlate with pCR. In an exploratory analysis we compared gene expression in IBC
      to non-inflammatory breast cancer; twenty-four (9%) of the genes were
      differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated
      in IBC. CONCLUSION: Gene expression analysis on core biopsy samples is feasible
      and identifies candidate genes that correlate with pCR to primary chemotherapy.
      Gene expression in IBC differs significantly from noninflammatory breast cancer.

PMID- 17039266
TI  - Breast cancer patients on adjuvant chemotherapy report a wide range of problems
      not identified by health-care staff.
AB  - BACKGROUND: Adjuvant chemotherapy for primary breast cancer is associated with
      significant side effects. The aims of this study were (1) to compare health
      related quality of life (HRQL) in patients undergoing adjuvant chemotherapy to
      patients not on chemotherapy and (2) to compare these results against a survey
      investigating health-care professionals' knowledge of HRQL. METHODS: Patients on
      adjuvant cyclophosphamide, methotrexate, fluoracil chemotherapy were compared to
      'low-risk' patients not on chemotherapy ('control group'). A questionnaire
      including the EORTC QLQ-C30, the Hospital Anxiety and Depression Scale (HADS),
      and the DBCG 89 Questionnaire was administered six times during a 2-year period.
      Forty-six experienced health-care professionals were asked which quality-of-life
      issues they thought were affected by adjuvant chemotherapy. RESULTS: After 2
      years, 159 of 242 patients on chemotherapy and 148 of 199 patients in the control
      group were alive and recurrence-free and had completed all questionnaires. Worse
      HRQL during chemotherapy was seen, as had been previously suggested, for 23 of 30
      variables. A number of the health-care professionals had not indicated patients
      to have these side effects. Several side effects persisted after the
      chemotherapy. CONCLUSIONS: This study provides the most comprehensive description
      of HRQL in adjuvant therapy to date. The discrepancy between patients and
      doctors/nurses suggests that patients have been insufficiently informed about the
      impact of chemotherapy on quality of life. The results of this study provide a
      basis for information that can be given to patients, and indicate that the care
      offered to patients in chemotherapy should seek to prevent, identify, and
      alleviate a very broad range of problems.

PMID- 17039267
TI  - A prospective study of adjuvant CMF in males with node positive breast cancer: 20
      year follow-up.
AB  - PURPOSE: To determine the long-term overall survival of male patients with stage
      II node positive breast cancer treated with adjuvant chemotherapy. PATIENTS AND
      METHODS: Between 1974 and 1988, 31 male breast cancer patients were prospectively
      enrolled on study MB-82 in the National Cancer Institute. Following mastectomy,
      patients were treated with 12 cycles of cyclophosphamide, methotrexate, and
      fluorouracil (CMF) chemotherapy. RESULTS: Median patient age was 61 years (38-74
      years). Twenty-one patients (68%) had 1-3 positive axillary lymph nodes while ten
      patients (32%) had four or more positive nodes. Estrogen receptor status was
      positive in 22 (71%), negative in 1 (3%), and unknown in 8 (26%) tumors.
      Progesterone receptor status was positive in 18 (58%), negative in 3 (10%), and
      unknown in 10 (32%) tumors. Median potential follow-up for all patients is 22.5
      years with a median survival of 16.3 years. Twenty-one of 31 patients have died;
      one from a treatment-related complication, nine patients from recurrent breast
      cancer, five from other cancers, one from non-cancer related causes, and five
      from unknown causes. Ten patients remain alive at a median of 19.2 years. The
      overall survival probability at 10 years is 64.5% (95% CI: 46.9-78.9%), at 15
      years is 51.6% (95% CI: 34.8-68%), and at 20 years is 42.4% (95% CI: 25.8-60.8%).
      CONCLUSION: To our knowledge, 20-year prospective data with adjuvant chemotherapy
      in male breast cancer has never been reported. Adjuvant chemotherapy may benefit
      male breast cancer patients with positive nodes.

PMID- 17039268
TI  - Gene expression profiling of breast cancer cells in response to gemcitabine: NF
      kappaB pathway activation as a potential mechanism of resistance.
AB  - Gemcitabine is a nucleoside analog with clinical relevance in the treatment of
      several solid tumors, including breast carcinoma. In spite of its cytotoxic
      effect, clinical efficacy is impaired by the development of resistance. We
      performed gene expression analysis to shed light into the molecular mechanism of
      action of this drug in two breast cancer cell lines. Activation of genes related
      with cell cycle, cell growth and apoptosis (BNIP3L, CCNG2, DDIT4, TGFB2, TP53BP1,
      TP53INP1, and VEGF) was the main finding in the p53-wild type cell line MCF7,
      while the p53-non-functional cell line MDA-MB-231 was characterized by the
      regulation of NF-kappaB target genes (BIRC3, CXCL1/GRO1, IRAK2, TNF, TNFAIP and
      TRAF1). Genes consistently induced (ATF3, CCNG2, CDKN1A, EGR1, INSIG1, and MAF)
      or repressed (CCND1 and VGF) in both cell lines, were also found after
      gemcitabine treatment. In addition, MDA-MB-231 cells showed a higher basal and
      induced NF-kappaB transcriptional activity after treatment with gemcitabine. In
      comparison with gemcitabine, gene expression after 5-fluorouracil treatment
      showed essentially different profiles in both cell lines. This, in spite of using
      equitoxic concentrations producing similar effects on cell cycle. NF-kappaB
      transcriptional activity in MDA-MB-231 cells was dependent on IkappaB-alpha
      phosphorylation, as shown by functional experiments using the specific inhibitor
      BAY11-7082. Moreover, immunohistochemical analysis of clinical samples of breast
      carcinoma further validated the induction of NF-kappaB expression and IkappaB
      down-regulation upon neoadjuvant gemcitabine treatment. Thus, gene expression
      patterns, in vitro functional studies and analysis of tissue samples are in
      agreement with a role for NF-kappaB pathway in gemcitabine response. Together
      with the reported role for NF-kappaB in the induction of resistance to
      chemotherapy, our data gives support to clinical strategies combining gemcitabine
      with NF-kappaB inhibitors in breast cancer.

PMID- 17039269
TI  - Very high incidence of familial colorectal cancer in Newfoundland: a comparison
      with Ontario and 13 other population-based studies.
AB  - Newfoundland has the highest rate of colorectal cancer (CRC) of any Canadian
      province. In order to investigate the factors, especially genetic components,
      responsible for CRC we established the Newfoundland Colorectal Cancer Registry.
      In a 5-year period we examined every case of CRC diagnosed under the age of 75
      years and obtained consent from 730 cases. Careful analysis of family history was
      used to assign a familial cancer risk, based on established criteria. We observed
      that 3.7% of CRC cases came from families meeting the Amsterdam II criteria and a
      further 0.9% of cases involved familial adenomatous polyposis (FAP). An
      additional 43% of cases met one or more of the revised Bethesda criteria and 31%
      of all cases had a first-degree relative affected with CRC. We compared the
      Newfoundland data with data from the province of Ontario, where the same
      recruitment and risk-assessment criteria were used. In all categories, the
      indicators of familial risk were significantly higher in Newfoundland. These data
      were also compared to results published from 13 other population-based studies
      worldwide. In every category the proportion of Newfoundland cases meeting the
      criteria was higher than in any other population. The mean differences were: 3.5
      fold greater for FAP, 2.8-fold higher for Amsterdam criteria, 2.0-fold higher for
      Bethesda criteria and 1.9-fold higher for the number of affected first-degree
      relatives. We conclude that the high incidence of CRC in Newfoundland may be
      attributable to genetic, or at least familial, factors. In the high-risk families
      we provide evidence for the involvement of founder mutations in the APC and MSH2
      genes.

PMID- 17039270
TI  - The natural history of a combined defect in MSH6 and MUTYH in a HNPCC family.
AB  - In the inherited syndromes, MUTYH-associated polyposis (MAP) and hereditary
      nonpolyposis colorectal cancer (HNPCC), somatic mutations occur due to loss of
      the caretaker function that base-repair (BER) and mismatch repair (MMR) genes
      have, respectively. Recently, we identified a large branch from a MSH6 HNPCC
      family in which 19 family members are heterozygous or compound heterozygous for
      MUTYH germ line mutations. MSH6/MUTYH heterozygote mutation carriers display a
      predominant HNPCC molecular tumour phenotype, with microsatellite instability and
      underrepresentation of G>T transversions. A single unique patient is carrier of
      the MSH6 germline mutation and is compound heterozygote for MUTYH. Unexpectedly,
      this patient has an extremely mild clinical phenotype with sofar only few
      adenomas at age 56. Four out of five adenomas show characteristic G>T
      transversions in APC and/or KRAS2, as seen in MUTYH associated polyposis. No
      second hit of MSH6 is apparent in any of the adenomas, due to retained MSH6
      nuclear expression and a lack of microsatellite instability. Although this
      concerns only one case, we argue that the chance to find an additional one is
      extremely small and currently a mouse model with this genotype combination is not
      available. Moreover, the patients brother who is also compound heterozygous for
      MUTYH but lacks the MSH6 germline mutation presented with a full blown polyposis
      coli. In conclusion, these data would support the notion that abrogation of both
      MSH6 DNA mismatch repair and base repair might be mutually exclusive in humans.

PMID- 17039272
TI  - A simple polymerase chain reaction-sequencing analysis capable of identifying
      multiple medically relevant filamentous fungal species.
AB  - Due to the accumulating evidence that suggests that numerous unhealthy conditions
      in the indoor environment are the result of abnormal growth of the filamentous
      fungi (mold) in and on building surfaces it is necessary to accurately determine
      the organisms responsible for these maladies and to identify them in an accurate
      and timely manner. Historically, identification of filamentous fungal (mold)
      species has been based on morphological characteristics, both macroscopic and
      microscopic. These methods may often be time consuming and inaccurate,
      necessitating the development of identification protocols that are rapid,
      sensitive, and precise. To this end, we have devised a simple PAN-PCR approach
      which when coupled to cloning and sequencing of the clones allows for the
      unambiguous identification of multiple fungal organisms. Universal primers are
      used to amplify ribosomal DNA sequences which are then cloned and transformed
      into Escherichia coli. Individual clones are then sequenced and individual
      sequences analyzed and organisms identified. Using this method we were capable of
      identifying Stachybotrys chartarum, Penicillium purpurogenum, Aspergillus
      sydowii, and Cladosporium cladosporioides from a mixed culture. This method was
      found to be rapid, highly specific, easy to perform, and cost effective.

PMID- 17039271
TI  - The phenotypic expression of three MSH2 mutations in large Newfoundland families
      with Lynch syndrome.
AB  - To compare the phenotypic expression of three different MSH2 mutations causing
      Lynch syndrome, 290 family members at 50% risk of inheriting a mutation were
      studied. Two truncating mutations of the MSH2 gene have been identified in
      Newfoundland: an exon 8 deletion in five families (N=74 carriers) and an exon 4
      16 deletion in one family (N=65 carriers). The third mutation was an intron 5
      splice site mutation resulting in deletion of exon 5 in RNA and occurred in 12
      families (N=151 carriers). Age to onset of first cancer, first colorectal cancer
      (CRC), first extracolonic cancers and death were compared. By age 60, 89% of
      family members with the intron 5 mutation, 81% with the exon 8 deletion, and 85%
      with the exon 4-16 deletion had developed cancer. For all three mutations males
      had a higher age-related risk of CRC and death compared to females. In the intron
      5 splice site mutation carriers, the number of transitional cell cancers of the
      urinary tract was significantly lower and time to first ovarian cancer was
      significantly higher than in the carriers of the genomic deletions. The incidence
      of CRC in MSH2 mutation carriers, exposed to the same environment, is not
      modified by the specific mutation, although there is a suggestion that type of
      mutation may influence development of some extracolonic cancers.

PMID- 17039273
TI  - Genotyping by RAPD-PCR analyses of Malassezia furfur strains from pityriasis
      versicolor and seborrhoeic dermatitis patients.
AB  - Malassezia furfur is lypophilic yeast commonly associate with dermatological
      disorders. In the present work, we described the isolation of 47 M. furfur
      strains from three groups of patients: pityriasis versicolor (21 isolates),
      seborrhoeic dermatitis (15 isolates) and seborrhoeic dermatitis of the HIV
      positive patients (11 isolates). To investigate the identity of the strains at
      molecular level, DNA genomic of M. furfur strains were prepared and used to RAPD
      PCR analyses. RAPD assay were carried out using two decamer primers and bands
      pattern generated were analyzed by an Unweighted Pair-Group Method (UPGMA).
      Dendrogram established a distinct differentiation between M. furfur isolates from
      pityriasis versicolor and seborrhoeic dermatitis patients with or without AIDS.
      We concluded that RAPD typing presented a high discriminatory power between
      strains studied in this work and can be applied in epidemiological investigation
      of skin disease causing by M. furfur.

PMID- 17039274
TI  - Majority of Actinomadura clinical isolates from sputa or bronchoalveolar lavage
      fluid in Japan belongs to the cluster of Actinomadura cremea and Actinomadura
      nitritigenes, and the description of Actinomadura chibensis sp. nov.
AB  - In Japan during 1996-2004, 21 actinomycete strains that have madurose as the
      diagnostic cell-wall sugar and show true branching in their substrate and aerial
      mycelia were isolated from sputa or bronchoalveolar lavage (BAL) fluid of
      patients with pulmonary infections or who were suspected of having related
      infections. Chemotaxonomic studies showed that all the isolates belong to the
      genus Actinomadura. Among them, six and seven strains were classified
      respectively into clusters of Actinomadura nitritigenes and Actinomadura cremea
      based on 16S rDNA analyses because their 16S rDNA similarities to those
      respective species were greater than 99.5%. To our knowledge, this is first
      report that strains of above two species were isolated from clinical specimens.
      Neither Actinomadura madurae nor Actinomadura pelletieri strain was isolated, and
      one new species, Actinomadura chibensis, was proposed; the remaining seven
      strains were not assigned into any known species, suggesting the presence of
      another new Actinomadura species.

PMID- 17039275
TI  - Saksenaea vasiformis infections: case report and literature review.
AB  - Since the first human infection by Saksenaea vasiformis in 1976 another 26 cases
      have been reported. Here is a report of a new case which involved an Ecuadorian
      adolescent who suffered serious burns after a car accident. It developed as a
      localized cutaneous infection which was successfully treated with surgical
      debridement and amphotericin B. This is the second report of this infection from
      South America and the third involving a burn patient. The previously reported 27
      cases are reviewed.

PMID- 17039276
TI  - A case of recurrent episodes of Candida parapsilosis fungemia.
AB  - Candida species is the fourth most commonly isolated organism in blood stream
      infections in the hospital setting. Patients with candidemia frequently succumb
      to this infection. For those that survive an initial candidemia, an increasing
      number of cases of breakthrough or recurrent candidemias have been reported in
      the literature. We report three episodes of C. parapsilosis fungemia in a cancer
      patient. Molecular testing was performed and confirmed that all these episodes
      occurring within an eight-month period were caused by the same organism. The
      incidence of recurrent candidemia is likely to increase in the near future.
      Studies and therapeutic interventions for patients at risk for recurrent
      candidemias are warranted.

PMID- 17039277
TI  - Resistant Microascus cirrosus pneumonia can be treated with a combination of
      surgery, multiple anti-fungal agents and a growth factor.
AB  - A 49-year old male with acute myelogenous leukemia relapsed eight years post
      allogeneic bone marrow transplantation. The patient received induction
      chemotherapy causing prolonged neutropenia. The patient developed pneumonia for
      which empirical antibacterial and antifungal therapy were started. The patient
      underwent a video-assisted thorocascopy with near complete resection of the
      lesion because of poor response to treatment. Microascus cirrosus was identified
      in the tissue. In vitro susceptibility test to different antifungal agents showed
      M. cirrosus was very resistant. The patient is undergoing second allogeneic
      transplant with improved pneumonia resulting from a combination of treatment for
      fungal infection, which included surgery, antifungal agents, and granulocyte
      colony stimulating factor. The Microascus genus rarely causes invasive fungal
      infection in humans and can be very difficult to treat because of the resistance
      to available antifungal agents.

PMID- 17039278
TI  - Keratinophilic fungi from the vicinity of meteorite crater soils of Lonar
      (India).
AB  - Thirty-two soil samples were collected from six sites in the vicinity of Lonar
      lake, a meteorite crater and screened for presence of keratinophilic fungi using
      hair baiting techniques for isolation. Seventeen isolates were recovered and
      identified. The cultures were identified by recognition of their macro- and
      micromorphological features. Their identification was also confirmed by the BLAST
      search of sequences of ITS1-5.8S-ITS2 rDNA region against the NCBI/Gene bank data
      and compared with deposited sequences for identification purpose. Seven species
      of four genera were isolated viz. Aphanoascus durus (9.38%), Aphanoascus punsolae
      (3.125%), Auxarthron kuehnii (3.125%), Chrysosporium indicum (25.00%),
      Chrysosporium tropicum (3.125%), Chrysosporium sp. (3.125%), Chrysosporium state
      of Ctenomyces serratus (6.25%).

PMID- 17039279
TI  - Reduction of aflatoxin B1 in chicken feed by using Saccharomyces cerevisiae,
      Rhizopus oligosporus and their combination.
AB  - Aflatoxin B1 is a toxigenic and carcinogenic compound produced by Aspergillus
      flavus and Aspergillus parasiticus. An approach to prevent aflatoxin
      contamination in feed was carried out by using Saccharomyces cerevisiae (Sc) and
      Rhizopus oligosporus (Ro). Aspergillus flavus was cultured together with Sc, Ro
      and their combination (ScRo) in chicken feed. The aflatoxin B1 content was
      observed at day 0, 5, 10 and 15. The result showed that aflatoxin B1
      contaminations in feed were reduced by Sc, Ro and ScRo addition. The highest
      reduction of aflatoxin B1 content was shown at day 5 for all treatments with Sc,
      Ro and ScRo. The best activity of reducing aflatoxin B1 was shown by Ro. Although
      the ability of reducing aflatoxin B1 of Sc, Ro or ScRo was not significantly
      different, Sc or Ro gave the better result than ScRo and they are better used
      individually.

PMID- 17039280
TI  - Mycocin production in Pseudozyma tsukubaensis.
AB  - Killer activity expressed at pH values ranging from 3.5 to 6.0 was found in the
      ustilaginaceous yeast-like species, Pseudozyma tsukubaensis. Its killer phenotype
      was incurable, and extrachromosomal genetic elements were not detected. The toxin
      excreted with a molecular mass above 15 kDa is fungicidal, resistant to
      proteolytic cleavage, thermolabile and active only against fungi within the
      Ustilaginomycetes (the orders Microstromatales and Ustilaginales).

PMID- 17039281
TI  - Fosinopril and carvedilol reverse hypertrophy and change the levels of protein
      kinase C epsilon and components of its signaling complex.
AB  - OBJECTIVE: To demonstrate the alterations of Protein Kinase C epsilon (PKC
      epsilon) and components of its signaling complexes after treatment with
      fosinopril and carvedilol and analyze potential molecular mechanisms of the two
      drugs for cardiac hypertrophy and heart failure. METHODS: Pressure-overload
      cardiac hypertrophy (POH) was developed in 8-week-old male Sprague Dawley rats by
      abdominal aortic banding. The rats were divided into three groups at the age of
      20 weeks: POH without failure group, reversed POH with drugs group, and POH with
      failure group on high diet. Western Blot analysis, co-immunoprecipitation and
      proteomic analysis were performed in ventricular tissues of rat hearts. RESULTS:
      Increased PKC epsilon was found during POH. PKC epsilon decreased during
      transition from POH to heart failure (HF). However, increased PKC epsilon
      inclined to recover to normal levels after treatment with both drugs. There were
      differential proteins in PKC epsilon complexes during the different stages of
      POH. The two significant PKC epsilon-binding proteins, MAD1 and Lyn A, were only
      present in PKC epsilon complex during reversing POH with drugs. CONCLUSION:
      Chronic administration of carvedilol and fosinopril could reverse the development
      of POH and delay the appearance of HF, partly by regulating PKC epsilon level and
      its signaling complex. MAD1 and Lyn A may be important proteins participating in
      the reversing process.

PMID- 17039282
TI  - RBx 7,796: A novel inhibitor of 5-lipoxygenase.
AB  - OBJECTIVE: To evaluate the pharmacological profile of RBx 7,796, a novel 5
      lipoxygenase inhibitor. MATERIALS AND METHODS: RBx 7,796 was evaluated for 5-
      lipoxygenase inhibitory potential using human recombinant enzyme and profiled for
      selectivity against 12 and 15 lipoxygenase. RBx 7,796 was evaluated in cell based
      assay for inhibition of A23,187 induced LTB(4) release from isolated neutrophils.
      Ex vivo activity was evaluated for inhibition of A23,187 induced LTB(4) release
      in blood from treated rats. In vivo efficacy of RBx 7,796 was profiled in LPS
      induced neutrophilia model in rats and also in ovalbumin induced
      bronchoconstriction and airway inflammation models in guinea pigs. RESULTS: RBx
      7,796, a novel chemotype, showed competitive inhibition of 5-lipoxygenase enzyme
      with an IC(50) of 3.5 +/- 1.1 microM. RBx 7,796 offered >100 fold selectivity
      against other related enzymes - 12 and 15 lipoxygenase. RBx 7,796 inhibited
      release of LTB(4) from human and rat neutrophils in vitro. Upon administration to
      rats, RBx 7,796 inhibited A23,187 induced LTB(4) release from rat neutrophils.
      Upon repeated administration, dosed once daily, RBx 7,796 inhibited LPS induced
      neutrophil influx in rat airway. RBx 7,796 also inhibited allergen induced
      bronchoconstriction and eosinophil influx in guinea pig airway in a dose
      dependent manner. CONCLUSION: The results suggest that RBx 7,796, a novel
      chemotype, is an orally efficacious inhibitor of 5-lipoxygenase enzyme that is
      effective against both neutrophilic and eosinophilic airway inflammation and
      shows potent inhibition with once daily administration.

PMID- 17039283
TI  - Transforming growth factor-beta stimulates IL-1beta-induced monocyte
      chemoattractant protein-1 expression in human synovial cells via the ERK/AP-1
      pathway.
AB  - OBJECTIVE AND DESIGN: Transforming growth factor- beta (TGF-beta) has not only a
      fibrogenic role, but also monocyte/ macrophage chemotactic properties in a
      synovial joint. However, little is known about the effects of TGF-beta on
      monocyte chemoattractant protein-1 (MCP-1) expression in human synovial cells
      under inflammatory status. The aim of this study was to determine whether TGF
      modulates MCP-1 production under the chronic inflammation, and to elucidate the
      cell signaling mechanism involved. MATERIALS AND METHODS: Human synovial cells
      were exposed to IL-1beta, which mimics the environment of chronic inflammation.
      Production of MCP-1 protein and expression of MCP-1 mRNA were determined by ELISA
      and real-time PCR. RESULTS: TGF-beta upregulated the expression of MCP-1 mRNA and
      protein with or without IL-1beta. TGF-beta and IL-1beta synergistically enhanced
      MCP-1 gene expression, and an AP-1 binding site was involved in the signal
      transduction. In addition, MEK inhibitor completely suppressed TGF-beta-induced
      MCP-1 production. CONCLUSIONS: TGF-beta and IL-1beta synergistically enhance MCP
      1 gene expression through the activation of the MEK/ERK1/2 pathways, which leads
      to AP-1 activation. The impairment of MCP-1 regulation by TGF-beta in resident
      synovial cells might represent an important mechanism of chronic inflammation and
      tissue fibrosis in a synovial joint. MCP-1 should be considered a valid target
      for therapeutic intervention.

PMID- 17039284
TI  - Concentrations of CXCL8, CXCL9 and sTNFR1 in plasma of patients with pulmonary
      tuberculosis undergoing treatment.
AB  - BACKGROUND: Chemokines are a class of cytokines with chemotactic properties shown
      to be induced by M. tuberculosis or its antigens in vitro and in experimental
      infection in vivo. A few studies have also demonstrated the expression of
      chemokines in clinical samples of patients with active tuberculosis (TB). In the
      present work, we measured the concentration of chemokines in plasma samples of
      HIV-negative patients with pulmonary tuberculosis at different stages of
      chemotherapy. For comparison, we also evaluated the levels of sTNFR1 and TNF
      alpha. METHODS: Cytokines and chemokines were measured by ELISA in healthy
      individuals and patients with active pulmonary TB at different stages of
      treatment. RESULTS: The concentrations of CXCL8, CXCL9 and sTNFR1 were elevated
      in patients with active pulmonary TB but returned to background levels at 4-6
      months of chemotherapy. The concentration of CCL11 was elevated in patients with
      active pulmonary tuberculosis when compared to control and remained elevated
      throughout the specific therapy. There was no difference in the plasma
      concentration of CCL2 and CXCL10 between pulmonary TB patients and control
      subjects. CONCLUSION: Measurement of the CXCL8, CXCL9 and sTNFR1 may be useful to
      assess response to treatment in pulmonary TB patients.

PMID- 17039285
TI  - Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor
      deficient mice.
AB  - BACKGROUND: Sesamin, a major lignan from sesame seeds has been associated with
      cholesterol reduction in previous reports, but recent studies suggested
      differences in the response to sesamin intake depending on the model studied as
      well as the nature of the sesamin preparation used. AIM: The effect of pure
      sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor
      knockout mice under cholesterol fed condition. DESIGN: Animals were randomly
      assigned to 4 groups, fed an atherogenic diet containing stanol ester, sesamin,
      combination of stanol ester and sesamin or a control diet with no additions.
      RESULTS: The control group showed an almost 3-fold increase in serum cholesterol
      levels due to the atherogenic diet but no effect was seen for triglyceride
      levels. Stanol ester alone or together with sesamin significantly attenuated the
      elevation of the cholesterol levels. CONCLUSION: Sesamin alone did not affect the
      elevation of the diet-induced cholesterol level and it did not enhance the effect
      of stanol ester.

PMID- 17039286
TI  - [Quality of health care of the elderly].

PMID- 17039287
TI  - Health care in seniority: crucial questions and challenges from the perspective
      of health services research.
AB  - This paper gives an updated outlook on geriatric health care in Germany and on
      research demands with particular respect to advanced-age patients with
      multimorbidity. The paper is written from the perspective of health services
      research and addresses selected topics such as primary care, palliative care,
      health policies and patient orientation. It is pointed out that the structure of
      services and processes of health care delivery is not compatible with the complex
      demands of the target group, and that the priorities of improvement strategies
      may differ among the various professional groups involved (e. g. primary care
      physicians as generalists and palliative and geriatric experts as specialists).
      Furthermore, it is argued that the current incentives for establishing integrated
      health care may not be adequate to ensure that sustainable changes are made in
      the long term.

PMID- 17039288
TI  - [Psychopharmacological drug treatment in Munich nursing homes].
AB  - The survey of Munich nursing homes with 888 residents showed that 56.4% received
      psychotropic drugs and a twice as frequent prescription of antipsychotics to
      residents of double rooms than of single rooms. In a subsample of 397 residents
      the last review of the prescriptions of 17.5% of the psychotropic drugs was at
      least 3 months to partly years ago. Based on the American Beers-criteria 13.6% of
      the consumers of psychotropic drugs received psychotropic drugs, which preferably
      should not be taken by older people.

PMID- 17039289
TI  - [Age differences in psychosocial resources and psychological well-being of cancer
      patients at the start of chemotherapy].
AB  - It has been suggested that older patients would have fewer resources than younger
      patients. We assessed psychosocial resources in 361 recently diagnosed cancer
      patients. Older patients had a stronger internal health-related locus of control
      but also less hope than younger patients. No age differences were found for self
      esteem and perceived social support. In addition, older patients reported lower
      levels of negative and positive affect. Curative-intended therapy and social
      support were associated with a more positive affect only in younger patients,
      whereas hope was only related to older patients' psychological well-being. It is
      concluded that older cancer patients have similar levels of psychosocial
      resources compared to younger patients, but that lack of hope is a vulnerability
      factor for older patients in particular.

PMID- 17039290
TI  - [The impact of different reference groups for the assessment of quality of life
      in people suffering from dementia-determination of competence groups with HILDE].
AB  - The HILDE project proceeds from a theoretical conception of quality of life which
      considers both the significance of objective living conditions claimed in the
      Swedish level of living approach and the significance of processes of subjective
      perceptions and judgements accentuated in the American quality of life approach.
      Since component definitions of quality of life regularly fail to reflect
      empirical relationships between the differentiated aspects, quality of life is
      defined as a constellation of personal and environmental material and immaterial
      resources and subjective wellbeing. Under the assumption that an adequate
      assessment of quality of life of people with dementia can not exclusively be
      based on their cognitive impairment, i.e. their stage of the disease, but must
      also reflect the realisation of individual preferences in a given life situation,
      the empirical portion of this contribution identifies and independently cross
      validates in random subsamples four patterns of competence in a sample of 362
      nursing home residents suffering from dementia. Each of these four different
      dementia syndrome groups is characterised by specific needs and values. They can
      be used as a point of reference within as well as between these competence
      groups, in order to plan individual interventions with competence-oriented
      expectations.

PMID- 17039291
TI  - [Communication training for family caregivers of dementia patients].
AB  - The program Kommunikations-TAnDem was developed with the primary purpose of
      increasing the communication competence of family caregivers of dementia
      patients. Further aims were to reduce the burden of family caregivers and to
      increase the quality of life of dementia patients. The effectiveness of the
      Kommunikations-TAnDem was tested in a controlled training study with 22
      participants using a waiting-group control design and process measurement. The
      results of the study verify effects for the variables "Communication competence",
      "Caregivers knowledge about communication in dementia", "Quality of life of
      dementia patients" and "Directly perceived burden of family caregivers. Therefore
      it can be concluded that the Kommunikations-TAnDem is a method of indirectly
      supporting dementia patients by training the family caregivers. The results of
      research in this program underline very clearly the relevance of the inclusion of
      the family caregivers in intervention programs and the importance of
      communication competence for the well-being of dementia patients and their
      caregivers.

PMID- 17039292
TI  - [Rehabilitation processes and sustainability: first results of a rehabilitation
      study of geriatric stroke patients].
AB  - A rehabilitation care management oriented towards the severity of the disease,
      the individual competence and the patient's needs essentially improves the
      effectivity and the sustainability of inpatient rehabilitation. The Institute of
      Gerontology of the University of Heidelberg is developing an assessment for
      elderly stroke patients to optimize placement decision by an early rehabilitation
      prognosis. Data concerning functional, cognitive and psychological status were
      collected in 267 patients participating in a postacute rehabilitation program on
      admission, after two weeks and on discharge and six weeks later. In this article
      are presented the study design and patients' characteristics during the
      rehabilitation process. The first assessment at admission gives important
      information about the sustainability of the ADL-competence after discharge.
      Severe stroke, premorbid ADL-competence, cognitive impairment, communication
      problems, depression and higher age were found to be predictors for the outcome
      of the rehabilitation process.

PMID- 17039293
TI  - Advance directives: prerequisites and usefulness.
AB  - Advance directives allow competent persons to extend their right of self
      determination into the future, by recording choices that are intended to
      influence their future care should they become unable to make choices. They are
      considered tools to facilitate end-of-life decision making. Advance directives
      are a form of anticipatory decision-making. This article will focus on
      instruction directives against a certain treatment, so-called advance refusals.
      The most important legal requirement is the acknowledgement of patient autonomy.
      This condition is met in all European countries. The legal uncertainties
      surrounding advance refusals are focused on practical modalities rather than on
      the validity of the general principle. According to leading ethics the underlying
      moral rule of advanced directives is that all truly autonomous refusals of
      treatment must be respected, no matter what the consequences. Physicians find it
      hard to adhere to the wishes and choices of patients as expressed in directives.
      They find the text ambiguous. Another weakness is that directives give little
      information about what in the patient's view constitutes a good quality of life.
      Some health professionals lack the willingness to step outside their own value
      systems and fully embrace that of the patient. Empathic skills are required. Very
      few persons create an advance directive. Furthermore, of the created directives
      only some are accessible when patients are admitted to hospital. However, when
      directives are available they usually influence medical treatment decisions.

PMID- 17039294
TI  - [Palliative care in nursing homes: central issues and further research].
AB  - Palliative Care and the Hospice Movement meet many of the challenges nursing
      homes are currently faced with. There are different approaches dependent on the
      rules and culture of the national health care systems. The reviewed literature
      shows that Palliative Care in Nursing Homes lacks quality, especially in the care
      given to residents with dementia. Apart from that, a palliative culture in the
      organizations has to be developed. In this paper, central issues and topics for
      further research to improve Palliative Care in Nursing Homes are presented.

PMID- 17039295
TI  - [Sexual victimization in old age].
AB  - A study on the underresearched topic of elderly sexual victimization combined
      multiple data sources: German police crime statistics, 122 public prosecutor
      files on sexual victimization of people above age 60, survey data from 76
      institutions assisting victims of sexual violence/domestic violence, in-depth
      interviews with 22 practitioners who had worked with sexually victimized elderly.
      The study shows that few cases of sexual victimization in old age are known to
      law enforcement agencies or victim services. Offences dealt with by the criminal
      justice system differ significantly from those known to battered women's shelters
      and victim services. The majority of incidents prosecuted by the criminal justice
      system are hands-off offences; hands-on offences are typically single incidents
      committed by strangers or loose acquaintances of the victim. Battered women's
      shelters and institutions of victim assistance are confronted with severe forms
      of sexual violence in intimate relationships, the prototypical case being an
      older woman who is repeatedly victimized by her husband over a considerable
      period of time and within a relationship characterized by a comprehensive system
      of violence, humiliation, and control (corresponding to Johnson's concept of
      intimate terrorism). The study demonstrates how small numbers of recorded cases
      of sexual violence in old age may reflect age-specific detection rates. It
      provides evidence on older victims' help-seeking behavior and on ways to improve
      victim services.

PMID- 17039297
TI  - [Announcements of the BAG].

PMID- 17039296
TI  - [Announcements of the DGGG].

PMID- 17039299
TI  - Alzheimer 100--highlights in the history of Alzheimer research.
AB  - Alzheimer disease, a progressive neurodegenerative disorder of hitherto unknown
      etiology leading progressively to severe incapacity and death, has become the
      pandemic of the 21(st) century. On World Alzheimer Day, September 21, 2006, the
      100(th) anniversary of the first description of the clinical and histological
      findings in this disorder by A. Alzheimer, was celebrated. This retrospective
      review of the most important events and advances in Alzheimer research presents
      its early history in which only clinical and histologic signs of this peculiar
      disease were described. Electron microscopy, quantitative morphology and modern
      biochemistry emerging in the second half of the 20(th) century opened a new era
      in dementia research with description of the ultrastructure and biochemistry of
      senile plaques and neurofibrillary tangles, the major disease markers of AD.
      Advances in the development of clinical, neuropathological, and neuroimaging
      criteria, modern instruments and algorithms in the diagnosis of the disorder
      followed, enabling long-term studies and more exact diagnosis of AD and related
      disorders. Landmark studies were the development of operational criteria for the
      post mortem diagnosis of AD based on semiquantitative assessment and
      developmental patterns of its major markers. Basic research gave insight into the
      molecular genetics and pathophysiology of AD, and, based on the biochemical
      findings, new pharmacological treatment options were opened. Recently, biological
      and other surrogate, in particular functional neuroimaging, markers allow an
      early detection of presymptomatic stages of AD, their risk factors and
      progression which, in the future, might be prevented or at least slowed by new
      therapeutic approaches. Since the etiology of AD is hitherto unknown, causative
      therapies are still not available. The paper discusses future research needs and
      challenges for developing new diagnostic strategies for early and accurate
      detection of neurodegenerative processes leading to dementia, better
      epidemiologic and gender data as well as more insights into the pathogenic
      cascade of AD and other dementing disorders which will depend on international
      networks and close cooperation between clinicians, neuroscientists, caregivers,
      public health institutions, and individual sponsors.

PMID- 17039301
TI  - Treatment of hydrocephalus with functionally isolated ventricles.
AB  - Rapid therapeutic drainage of one lateral ventricle may lead to ipsilateral slit
      ventricle, and the resultant functional obstruction of cerebrospinal fluid flow
      through the foramen of Monro may cause dilatation of the contralateral ventricle.
      Drainage of the lateral ventricle with a low-pressure shunt led to functionally
      isolated contralateral ventriculomegaly in this report. The patient's condition
      was complicated by a Candida albicans shunt infection. Following effective
      treatment of the infection by chemotherapy and removal of the shunt system, the
      patient was treated by bridging two lateral ventricles with ventricular catheters
      connected to an Ommaya reservoir. An occipital ventricular catheter was then
      inserted and connected to a programmable valve to drain the bridged lateral
      ventricles. Modern centers, caring for patients with infantile hydrocephalus,
      should have endoscopic facilities available but in cases with extensive
      ventricular adhesions and in asymmetric hydrocephalus where endoscopic septostomy
      between the ventricles is impossible our described technique may be used.

PMID- 17039300
TI  - Auditory event-related potentials in subcortical vascular cognitive impairment
      and in Alzheimer's disease.
AB  - BACKGROUND: Few studies exist on ERPs and patients with subcortical vascular
      cognitive impairment (SVCI). This latter is a quite homogeneous subtype of
      vascular dementia whose cognitive profile is quite different from that of
      Alzheimer disease (AD). AIMS: The present study aims at comparing the ERPs
      profile both in patients with SVCI and in patients with AD. SUBJECTS AND METHODS:
      ERPs and psychometric tests were collected from 39 healthy elderly controls, 51
      patients with SVCI and 43 patients with AD. Subjects mentally count high pitched
      target tones that were randomly intermixed with low pitched frequent tones. We
      measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1
      P2, N1-N2). RESULTS: Grand averaged potentials in SVCI showed a significant
      increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3
      latencies. As far as interpeak latencies are concerned, SVCI patients showed a
      significant prolongation of N1-P3, AD patients had a significant increase of N1
      N2, and N1-P3 intervals. When all patients were considered as a single group,
      correlation of neuropsychological tests scores showed a significant negative
      relationship between P300 latency and, respectively, Mini Mental Status
      Examination, auditive and visual span forward. In both groups, ERPs latency
      sensitivity, was low, whilst specificity values were quite high. CONCLUSIONS: Our
      finding suggest that these two dementing diseases have different
      electrophysiologic features that may be related to their specific underlying
      pathogenetic mechanism; in particular, we hypothesise that, differently from AD,
      P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs
      approach could be helpful to detect early alterations of the attentional/working
      memory functions in patients with subcortical ischaemic vascular disease.

PMID- 17039302
TI  - Injection therapy of lumbar facet syndrome: a prospective study.
AB  - BACKGROUND: Chronic low back pain remains a major health problem. Facet joint
      injection therapy is an easy to perform therapeutic option. However, few
      prospective studies use a standardized protocol to investigate injection therapy.
      The aim of our study was to evaluate quantity and duration of clinical
      improvement after this protocol, and to identify the best time for additional
      repetitive injection therapy. MATERIALS AND METHODS: Thirty-nine patients (21
      men, 18 women; mean age 55.2 years [range, 29-87 years]) with lumbar facet
      syndrome were treated with injection using a standardized protocol (prednisolone
      acetate, lidocaine 1%, phenol 5%) under fluoroscopic control. Follow-up was based
      on a specially designed questionnaire. Analysis included MacNab criteria, visual
      analogue scale, and pain disability index. RESULTS: Reduction of pain was found
      up to 6 months after treatment. The outcome was assessed excellent or good by 62%
      (24 patients) of the patients after 1 month, by 41% (16 patients) after 3 months,
      and by 36% (14 patients) after 6 months. There was no influence of age, body mass
      index, or previous lumbar spinal surgery on improvement after treatment. There
      were no severe side effects. Short-lasting self limiting mild side effects were
      found in 26% (increased back pain, numbness, heartburn, headache, allergy).
      CONCLUSION: Facet joint injection therapy using a standardized protocol is safe,
      effective, and easy to perform. The clinical effect is limited, and we recommend
      repetitive injection according to this protocol after 3 months.

PMID- 17039303
TI  - Intracranial pulse pressure amplitude levels determined during preoperative
      assessment of subjects with possible idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND: It was previously reported that the intracranial pulse pressure
      amplitudes were elevated in idiopathic normal pressure hydrocephalus (iNPH)
      patients responding to shunt surgery. In this study, pulse pressure amplitudes
      were determined in all patients referred for tentative iNPH, and patients were
      selected for shunt surgery based on the determination of their threshold levels
      of intracranial pulse pressure amplitudes. PATIENTS AND METHODS: All patients
      referred to our department for tentative iNPH during a 12 months time period were
      included. Using intracranial pressure (ICP) monitoring the intracranial pulse
      pressure amplitudes were determined as the mean wave amplitude in consecutive 6
      seconds time windows. Intracranial pulse pressure amplitudes were defined as
      being elevated when the mean wave amplitudes were either >or=4 mmHg in >or=70%,
      >or=5 mmHg in >or=40% or >or=6 mmHg in >or=10% of the ICP recording time. Shunt
      treatment was offered to those with elevated mean wave amplitudes. Clinical state
      was assessed by using a NPH Grading Scale and the Stein-Langfitt scale before ICP
      monitoring, and then repeated after 12 months. RESULTS: Among the 40 iNPH
      patients included during the 12 months period, the mean wave amplitudes were
      elevated in 24 patients (60%), while not being elevated in 16 (40%). Neither pre
      operative clinical state, radiological ventricular size nor co-morbidity differed
      between patient groups with elevated or non-elevated mean wave amplitudes. In the
      shunted patients who had pre-operatively elevated mean wave amplitudes, 91% had
      very significant clinical change after 12 months (median change in NPH score +4).
      In those with non-elevated amplitudes and no shunt, clinical state was somewhat
      worse after 12 months (median change in NPH score -1). CONCLUSIONS: In this one
      year material, mean wave amplitudes were elevated in 60% of iNPH patients. In
      those with elevated mean wave amplitudes who were treated with shunt, 91% had a
      significant clinical response.

PMID- 17039304
TI  - Intrasellar paraganglioma: a case report and review of the literature.
AB  - Intrasellar paragangliomas are very rare lesions with only six previous cases
      described in the literature. We present a further case of intrasellar
      paraganglioma. The patient was a 52 yr-old man who developed two transient
      ischemic attacks. A CT scan showed an intra- and supra-sellar expanding lesion,
      which was regarded as a possible non-functioning pituitary macro-adenoma. Removal
      of the lesion was accomplished by transsphenoidal surgery. Histological
      examination was diagnostic of a paraganglioma. We review the literature and
      discuss pathological features and possible pathogenesis of sellar and parasellar
      paragangliomas, underlining the necessity to consider paraganglioma in the
      differential diagnosis of sellar lesions.

PMID- 17039305
TI  - Primary germinoma arising from the midbrain.
AB  - A 29-year-old man presented with diplopia, dysarthria, anisocoria, oculomotor
      nerve paralysis, abducens nerve paralysis, right facial palsy, and spastic
      hemiparetic gait. Magnetic resonance imaging (MRI) showed a homogenously enhanced
      mass in the midbrain. MRI-guided stereotactic biopsy was performed, and the
      histologic diagnosis was pure germinoma. The tumor disappeared after chemotherapy
      and radiotherapy. Germinoma should be included in the differential diagnosis of
      midbrain lesions in young adults. MRI-guided stereotactic biopsy provided a
      helpful diagnostic clue in a patient with a midbrain lesion.

PMID- 17039298
TI  - The significance of the cholinergic system in the brain during aging and in
      Alzheimer's disease.
AB  - Acetylcholine is widely distributed in the nervous system and has been implicated
      to play a critical role in cerebral cortical development, cortical activity,
      controlling cerebral blood flow and sleep-wake cycle as well as in modulating
      cognitive performances and learning and memory processes. Cholinergic neurons of
      the basal forebrain complex have been described to undergo moderate degenerative
      changes during aging, resulting in cholinergic hypofunction that has been related
      to the progressing memory deficits with aging. Basal forebrain cholinergic cell
      loss is also a consistent feature of Alzheimer's disease, which has been
      suggested to cause, at least partly, the cognitive deficits observed, and has led
      to the formulation of the cholinergic hypotheses of geriatric memory dysfunction.
      Impaired cortical cholinergic neurotransmission may also contribute to beta
      amyloid plaque pathology and increase phosphorylation of tau protein the main
      component of neurofibrillar tangles in Alzheimer's disease. Understanding the
      molecular mechanisms underlying the interrelationship between cortical
      cholinergic dysfunction, beta-amyloid formation and deposition, and tau pathology
      in Alzheimer's disease, would allow to derive potential treatment strategies to
      pharmacologically intervene in the disease-causing signaling cascade.

PMID- 17039306
TI  - Application of cellular gene therapy for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common autoimmune disease characterized by
      persistent inflammation of joints resulting in progressive destruction of
      cartilage and bone. Recently, biological agents that suppress the activities of
      proinflammatory cytokines have shown efficacy as antirheumatic drugs, but require
      frequent administration, and often result in systemic immune suppression. Thus,
      gene transfer approaches are being developed as an alternative approach for
      targeted, more efficient, and sustained delivery of inhibitors of inflammatory
      cytokines as well as other therapeutic agents. Several gene therapy approaches
      have been established in preclinical animal models. In these models, autoantigen
      specific T cells have been demonstrated to be ideal gene delivery vehicles for
      the local delivery of "immunoregulatory molecules" because these cells have
      tissue-specific homing and retention properties. Indeed, bioluminescence studies
      in an animal model of inflammatory arthritis revealed that these cells
      accumulated in and remained in inflamed joints. Transfer of genetically modified
      dendritic cells (DCs) may also have interesting effects. We conclude that
      modifying antigen-specific T cells or autologous DCs by retroviral transduction
      for local expression of regulatory proteins is a promising therapeutic strategy
      for the treatment of RA.

PMID- 17039307
TI  - Autoimmunity to citrullinated type II collagen in rheumatoid arthritis.
AB  - The production of autoantibodies to citrullinated type II collagen and the
      citrullination of type II collagen were analyzed in rheumatoid arthritis.
      Autoantibodies to citrullinated type II collagen were detected in 78.5% of serum
      samples from 130 rheumatoid arthritis patients. Autoantibodies to native
      noncitrullinated type II collagen were detected in 14.6% of serum samples, all of
      which were positive for anti-citrullinated type II collagen antibodies. Serum
      samples were also positive for anti-citrullinated type II collagen antibodies in
      1 of 31 systemic lupus erythematosus patients and 2 of 55 patients with
      osteoarthritis of the knee. In contrast, sera samples from 24 systemic sclerosis
      patients, 21 dermatomyositis/polymyositis patients, 21 ankylosing spondylitis
      patients, and 18 psoriatic arthritis patients were all negative for anti
      citrullinated type II collagen antibodies. Anti-citrullinated type II collagen
      antibodies and fragments of citrullinated type II collagen were found in the
      synovial fluid obtained from affected knee joints of 15 rheumatoid arthritis
      patients. Moreover, anti-citrullinated type II collagen antibodies were isolated
      from the synovium of affected knee joints in 8 rheumatoid arthritis patients
      using antigen/antibody immunocomplex dissociation buffer but not by using
      standard buffers. These findings indicate that autoantibodies that react with
      citrullinated type II collagen are specifically produced and that immunocomplexes
      composed of fragments of citrullinated type II collagen and autoantibodies are
      deposited in the inflamed articular synovium in rheumatoid arthritis patients.
      Assaying for the presence of anti-citrullinated type II collagen antibodies may
      therefore be useful for diagnosing rheumatoid arthritis, and the deposition of
      these immunocomplexes in the articular synovium may be involved in pathogenesis.

PMID- 17039308
TI  - Evaluation of Pneumocystis pneumonia infection risk factors in patients with
      connective tissue disease.
AB  - We conducted a retrospective, clinical evaluation of connective tissue disease
      (CTD) patients who were tested for either sputum or bronchoalveolar lavage fluid
      Pneumocystis polymerase chain reaction (PC-PCR) and analyzed the risk factors
      that cause Pneumocystis pneumonia (PCP) susceptibility and fatality. PC-PCR was
      performed on 66 CTD patients who presented with symptoms, data, or radiological
      findings strongly suggesting respiratory infection. Patients with higher oral
      corticosteroid doses, use of oral methotrexate (MTX), bilateral lung findings,
      positive beta-D-glucan, and no prophylaxis use were more susceptible to PCP. They
      had significantly low immunoglobulin G and significantly high beta-D-glucan and
      lactate dehydrogenase. Survivors and nonsurvivors of PCP were also evaluated.
      Poor prognoses were observed with older age, elevated beta-D-glucan, rheumatoid
      arthritis (RA) patients using MTX, hypoxemia, bilateral lung findings, and
      mechanical ventilation use. Nonsurvivors had significantly lower lymphocytes,
      oxygen saturation, and significantly higher beta-D-glucan. In RA, poor prognoses
      were seen with those taking MTX. Disease duration, underlying pulmonary
      complications, and oral corticosteroid doses did not lead to poor prognoses in
      RA. Because PCP in CTD leads to abrupt onset of symptoms with poor survival
      rates, early diagnosis and initiation of treatment are critical, and it is
      essential for clinicians to recognize risk factors that predispose patients to
      PCP and its mortality.

PMID- 17039309
TI  - A biomechanical study of activities of daily living using neck and upper limbs
      with an optical three-dimensional motion analysis system.
AB  - In activities of daily living such as eating meals, the neck and upper limbs move
      in coordination. However, no methods have been established to analytically and
      quantitatively capture motion of the neck and limbs during these activities. We
      used a Vicon 512 system to simultaneously measure ranges of motion (ROMs) for the
      cervical spine, shoulders, elbows, and forearms. Correlations between the motion
      analyzer and the universal goniometer were >0.76. Repeatability of measurements
      using this analyzer were <or=3 degrees for all values. This system is thus highly
      accurate and can be useful for motion analysis of the neck and upper limbs. The
      sum of flexion angles for the cervical spine, shoulders and elbows were almost
      constant for each activity, at 261 degrees for shampooing, 207 degrees for
      washing the face, and 185 degrees for eating a meal.

PMID- 17039310
TI  - SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with
      rheumatoid arthritis.
AB  - To investigate the precise modality of association between SAA1 gene
      polymorphisms and the development of AA amyloidosis in patients with rheumatoid
      arthritis (RA), Japanese patients with RA (n=153), among whom 29 were
      histologically diagnosed as having amyloidosis, were genotyped for three single
      nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene.
      Pairwise linkage disequilibrium coefficients between each pair of SNPs were
      calculated and estimated haplotype frequencies were compared between patients
      with and without amyloidosis. Possible associations between these SNPs and
      amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method,
      in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The
      -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more
      frequent in the patients with amyloidosis, and the groups with the -13TT and
      2995CC genotype had worse survival curves than patients without these genotypes,
      whereas C3010T was not associated with amyloidosis. Moreover, the haplotype
      containing -13C and 2995T was found to be protective. Both C-13T and C2995T were
      associated with the development of amyloidosis. Examining both polymorphisms may
      be more useful than examining only one of them for estimating the risk of the
      development of amyloidosis.

PMID- 17039311
TI  - Acute effects of a single session of aerobic exercise with or without weight
      lifting on bone turnover in healthy young women.
AB  - This study aimed to investigate the acute effects of exercise on bone turnover
      and to determine whether brisk walking with or without weight-lifting makes a
      difference on bone metabolism. Nine healthy women performed two exercise bouts:
      brisk walking on a treadmill for 30 min (E), and similar exercise carrying 5 kg
      of weight in a backpack (WE). Serum parathyroid hormone (PTH), osteocalcin (OC),
      calcitonin (CT), procollagen type 1 carboxy terminal propeptide (PICP),
      procollagen type 1 amino terminal propeptide (PINP), type 1 collagen carboxy
      terminal telopeptide (ICTP), total alkaline phosphatase (ALP), and urine
      deoxypyridinoline (D-Pyr) levels were studied. Resting values served as control.
      Significant variances were observed only in serum ALP and PTH values. Variances
      in ALP values within subjects after exercise were statistically significant
      (analysis of variance in repeated measurements [AVRM], P=0.000). E caused a
      significant decrease, while WE caused a significant increase in ALP values at the
      24th h (Bonferroni pairwise comparisons tests [BPC t-test]: P=0.028, P=0.000,
      respectively). Variances in PTH values within subjects after exercise were
      statistically significant (AVRM, P=0.029), while diurnal variation was not
      significant (P=0.981). E caused significant alterations in PTH levels (an
      increase at the 30th min, turned towards baseline at the 45th min) (BPC t-test,
      P=0.007). WE also caused alterations in PTH levels, though insignificant (BPC t
      test, P=1.00). Brisk walking for 30 min has stimulating effects on bone turnover
      by various mechanisms without any additive effect of weight bearing.

PMID- 17039312
TI  - Klinefelter's syndrome associated with systemic lupus erythematosus and
      autoimmune hepatitis.
AB  - Klinefelter's syndrome (KFS) tends to be associated with immunological disorders.
      We describe a 37-year-old man who presented signs of testicular atrophy and
      decreased body hair. He showed pancytopenia and elevated levels of liver enzymes.
      Chromosome analysis revealed 47XXY karyotype; therefore, he was diagnosed with
      KFS, with systemic lupus erythematosus and autoimmune hepatitis. Treatment with a
      high dose of methylprednisolone and methyltestosterone improved thrombocytopenia
      and symptoms, suggesting that methyltestosterone may have a clinical benefit in
      the treatment of KFS with a low level of testosterone accompanying immunological
      disorders.

PMID- 17039314
TI  - Large benign rheumatoid nodules of the trunk in an elderly patient: radiologic
      appearance mimicking a soft-tissue sarcoma.
AB  - An 80-year-old woman without any evidence of rheumatoid arthritis presented with
      two large (maximum diameter: 6 cm and 7 cm), rapidly growing, rubbery nodules on
      the trunk. Although the clinical and radiological appearance suggested
      malignancy, the nodules were pathologically identical to rheumatoid nodules in
      rheumatoid arthritis, and the nodules regressed spontaneously. The final
      diagnosis was benign rheumatoid nodules. Recognition of this rare clinical entity
      is important to avoid unnecessary examination and treatment.

PMID- 17039313
TI  - Scleroderma renal crisis in a patient with anticentromere antibody-positive
      limited cutaneous systemic sclerosis.
AB  - We have encountered a 68-year-old Japanese woman with limited cutaneous systemic
      sclerosis who developed de novo onset of accelerated hypertension and renal
      dysfunction; thus we diagnosed scleroderma renal crisis. Anticentromere antibody
      alone was identified, and not anti-DNA topoisomerase I antibody, anti-RNA
      polymerase antibodies, anti-Th/To antibodies, or antiribonucleoprotein
      antibodies, even with use of immunoprecipitation assay. She was successfully
      treated with angiotensin-converting enzyme inhibitor. This case, scleroderma
      renal crisis with detection of anticentromere antibody, is thought to be
      extremely uncommon.

PMID- 17039315
TI  - Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid
      arthritis: autopsy findings with a mosaic pattern of acute and organizing diffuse
      alveolar damage.
AB  - We describe two cases of leflunomide-related interstitial pneumonia (IP). A 75
      year-old woman with rheumatoid arthritis (RA) developed rapidly progressing IP 45
      days after institution of leflunomide. She died of respiratory failure, and an
      autopsy revealed a mixed pattern of acute and organizing diffuse alveolar damage.
      A 69-year-old woman with RA also developed acute IP 3 months after institution of
      leflunomide. Methylprednisolone pulse therapy and cholestyramine ameliorated her
      IP. The implication of leflunomide in the pathogenesis of IP was suggested.

PMID- 17039316
TI  - A pediatric patient with neuro-Behcet's disease.
AB  - Behcet's disease is rare in childhood. We describe a 10-year-old boy with neuro
      Behcet's disease (NB) who presented with fever, headache, vertigo, and hearing
      loss. An examination of the cerebrospinal fluid (CSF) revealed pleocytosis as
      well as elevated protein and interleukin (IL)-6 levels. Brain magnetic resonance
      imaging (MRI) showed hyperintensity of the right thalamus and midbrain on T2-WI,
      and gadolinium (Gd) enhancement of left acoustic nerve origin. HLA-B51 was
      positive. Prednisolone combined with methotrexate resulted in a complete
      remission. Brain MRI and the CSF IL-6 level were useful for the diagnosis and
      monitoring of this pediatric patient with NB.

PMID- 17039317
TI  - Neglected spontaneous rupture of the Achilles' tendon in patients with systemic
      lupus erythematosus.
AB  - Spontaneous Achilles' tendon rupture associated with systemic lupus erythematosus
      (SLE) is rare complication in literature review. We encountered two patients with
      neglected spontaneous ruptures of Achilles' tendons who had been on
      corticosteroid therapy to treat SLE. The ages of these patients were 43 and 49
      years, and both were women. One of them was a case of bilateral Achilles' tendons
      rerupture. Achilles' tendons of both patients were reconstructed by surgery
      because of delay in their diagnosis. Histological section of the both ruptured
      Achilles' tendon revealed fibrotic scar tissue and little existence of
      inflammatory change. We concluded that careful diagnosis, surgical suture, and
      careful treatment after operation are necessary for Achilles' tendon rupture in
      those patients with SLE.

PMID- 17039318
TI  - Hypersensitivity reaction against influenza vaccine in a patient with rheumatoid
      arthritis after the initiation of etanercept injections.
AB  - A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high
      fever triggered by administration of an influenza vaccine after a 4-month-long
      effective treatment course with the TNF-alpha inhibitor etanercept. Influenza
      vaccine had been previously administrated safely to the patient before initiation
      of etanercept therapy. The fever occurred without other symptoms soon after
      vaccine administration, progressed to high fever 1 day later, and spontaneously
      resolved the second day. The clinical course appears to be compatible with drug
      fever closely associated with immediate hypersensitivity (in particular, late
      phase type I allergic reaction), in which T helper (Th) 2 cells play a crucial
      role. Etanercept can strongly suppress Th1-mediated reactions; therefore, Th2
      activity may be augmented by etanercept treatment in aspect of antagonism between
      Th1 and Th2 mechanisms. In RA patients who receive treatment with TNF-alpha
      inhibitor such as etanercept, activation of Th2-mediated immune responses such as
      immediate hypersensitivity may be a necessary side effect for those who receive
      vaccinations.

PMID- 17039319
TI  - Semiquantitative assessment of the intestinal motility in chronic intestinal
      pseudo-obstruction in systemic sclerosis and mixed connective tissue disease by
      Sitzmarks capsule.

PMID- 17039320
TI  - Coexistence of osteochondroma and reactive arthritis.

PMID- 17039321
TI  - [Characterization of proteinuria in patients with ulcerative colitis and therapy
      with aminosalicylates].
AB  - BACKGROUND AND PURPOSE: Patients with ulcerative colitis have a higher rate of
      tubular nephropathies. Data concerning the cause of these lesions is rare and
      inconsistent, the occurrence may be part of the disease itself or a side effect
      of 5-aminosalicylates (5-ASA). This study investigated proteinuria and
      eosinophiluria in patients with moderate ulcerative colitis under treatment with
      5-ASA. PATIENTS AND METHODS: Urine specimens (microelectrophoresis and
      eosinophiluria) of 34 patients with acute onset of moderate ulcerative colitis
      who were treated only with 5-ASA as active drug were analyzed. RESULTS: Data of
      27 patients could be evaluated. Twelve patients had tubular proteinuria previous
      to treatment. By the end of the study, urine specimens normalized in six, in
      further six the proteinuria remained unaltered, two patients developed
      proteinuria under treatment. In 14 patients, proteinuria was not detectable at
      any time. Eosinophiluria was found in none of the specimens. CONCLUSION: Under
      treatment with 5-ASA no toxic or allergic nephropathy developed. One initially
      pathologic urine specimen normalized under treatment coming along with remission
      of the intestinal symptoms and histological findings. This indicates an
      association between the activity of the ulcerative colitis and might be caused by
      renal excretion of pro-inflammatory cytokines.

PMID- 17039322
TI  - [Medical risk management].
AB  - An error-control management (management of technical errors) is well established,
      tested and approved in sectors of high risk, such as aviation and nuclear
      industry. Although medical science likewise represents a sector of high risk, a
      similar region-wide control management is still missing. The reasons are
      multifaceted: by implementation of an error-control management, the negotiation
      of psychological obstacles and the investment of financial resources have to be
      faced. The profit from overcoming these obstacles is gained only in the long
      term. The intention of this survey is to give an overview of the current state of
      knowledge of errors in medical science as well as to give an introduction
      (adoption) of the basic principles of systemic error description, detection and
      prevention by evaluating the available studies.

PMID- 17039324
TI  - [Diagnosis and differential diagnosis in patients with non-coronary chest pain].

PMID- 17039323
TI  - [Epidemiology and demographic evolution exemplified for cardiovascular diseases
      in Germany].
AB  - The interplay between demographic and epidemiologic evolutions is presented
      exemplified for cardiovascular diseases in Germany. The actually 82 million
      inhabitants of Germany build the frame for disease occurrence; currently, 2.1
      million men and 4.4 million women are > or = 75 years old. The ongoing increase
      of life expectancy to 75.6 years in men and 81.3 years in women was associated
      with a remarkable decrease of cardiovascular and ischemic heart disease (IHD)
      mortality and an increasing disease-specific mean age of death. Each third male
      and each fourth female death from IHD could be prevented, whereas the absolute
      number of nonfatal acute myocardial infarction (AMI) increased in the younger
      ages and decreased in the higher age groups. Since 1985, the total number of
      fatal and nonfatal cases of AMI has decreased by 24% in men and by 22% in women;
      two thirds of male and one third of female cases occur before the 75th year of
      age. These positive trends are mainly the result of a more effective acute and
      long-term therapy after AMI onset. Actually, 35% of all AMI patients do not
      survive the first day after acute onset and in up to 90% of them classic risk
      factors (hypertension, dyslipidemia, diabetes, cigarette smoking) were present.
      Therefore, the theme number 1 for the population must be intensified activities
      of primary prevention.

PMID- 17039325
TI  - [Interdisciplinary guidelines for diagnosis and therapy of extracerebral
      amyloidosis: issued by the German Society of Amyloid Diseases e. V.
      (www.amyloid.de)].

PMID- 17039326
TI  - [Chronic interstitial nephritis in an 18-year-old due to intake of a compound
      analgesic].
AB  - BACKGROUND: Renal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)
      are acute renal failure due to an impaired perfusion caused by inhibition of
      prostaglandin synthesis, acute allergic interstitial nephritis as well as acute
      toxic tubular necrosis. Moreover, chronic renal failure may occur due to a
      chronic interstitial nephritis or an analgesic nephropathy that is characterized
      by capillary sclerosis and papillary necrosis in addition to chronic interstitial
      nephritis. In contrast to acute renal insufficiency that may already occur after
      a single NSAID dose, analgesic nephropathy is a disease caused by long-term
      intake of NSAID compound analgesics and predominantly affects the middle and old
      age. CASE REPORT: An 18-year-old patient with a 4-year history of NSAID compound
      analgesic intake presented to the urology department with right-sided flank pain
      and increased serum creatinine. An obstruction as well as nephrolithiasis were
      ruled out and the patient was referred to the medical department. Urinalysis
      showed leukocyturia, mild microhematuria as well as proteinuria of 2.2 g/day
      whereupon a diagnostic kidney biopsy was performed. Histology revealed a chronic
      nonpurulent destructive interstitial nephritis. After cessation of analgesic
      intake, the serum creatinine level fell to the normal range; however, a reduced
      creatinine clearance persisted indicating chronic renal damage. CONCLUSION: The
      present case is remarkable in that chronic renal damage due to intake of a
      compound analgesic was already observed in an 18-year-old patient. In this
      context, the permission of NSAID compound analgesics and their free over-the
      counter sale to adolescents need to be critically questioned.

PMID- 17039327
TI  - [Cytomegalovirus-induced colitis in an immunocompetent old patient].
AB  - BACKGROUND: The cytomegalovirus (CMV) causes multiple diseases in patients with
      immunodeficiency. Also in patients with chronic inflammatory bowel disease,
      superinfections with CMV are known. Reactivation or infection is possible in rare
      cases in immunocompetent patients. CMV-induced colitis should be considered a
      differential diagnosis especially in patients suffering from diarrhea or bloody
      stools. CASE REPORT: The case of an 87-year-old patient with severe colitis is
      reported, who did not suffer from chronic inflammatory bowel disease nor from
      immunodeficiency. The most important hint came from the pathologist. The clinical
      outcome under antiviral therapy with ganciclovir was good. CONCLUSION: Even in
      immunocompetent patients, CMV-induced colitis should be taken into consideration,
      especially in elderly people.

PMID- 17039328
TI  - [The German program for disease management guidelines. Background, methods, and
      development process].
AB  - The Program for National Disease Management Guidelines (German DM-CPG Program)
      was established in 2002 by the German Medical Association (umbrella organization
      of the German Chambers of Physicians) and joined by the Association of the
      Scientific Medical Societies (AWMF; umbrella organization of more than 150
      professional societies) and by the National Association of Statutory Health
      Insurance Physicians (NASHIP) in 2003. The program provides a conceptual basis
      for disease management, focusing on high-priority health-care topics and aiming
      at the implementation of best practice recommendations for prevention, acute
      care, rehabilitation and chronic care. It is organized by the German Agency for
      Quality in Medicine, a founding member of the Guidelines International Network (G
      I-N). The main objective of the German DM-CPG Program is to establish consensus
      of the medical professions on evidence-based key recommendations covering all
      sectors of health-care provision and facilitating the coordination of care for
      the individual patient through time and across interfaces. Within the last year,
      DM-CPGs have been published for asthma, chronic obstructive pulmonary disease,
      type 2 diabetes, and coronary heart disease. In addition, experts from national
      patient self-help groups have been developing patient guidance based upon the
      recommendations for health-care providers. The article describes background,
      methods, and tools of the DM-CPG Program, and is the first of a publication
      series dealing with innovative recommendations and aspects of the program.

PMID- 17039329
TI  - [DRG and coding: alcoholism and withdrawal].

PMID- 17039330
TI  - Drug-induced granulomatous interstitial nephritis in a pediatric patient.
AB  - Acute interstitial nephritis (AIN) is a known cause of acute renal failure in
      children. In most instances, drug therapy is the offending agent. Although
      granuloma formation has been observed in drug-induced interstitial nephritis, it
      is not a commonly associated manifestation. This is a case of a 15-year-old white
      female with Tetralogy of Fallot and pulmonary atresia who developed acute renal
      failure secondary to drug-induced interstitial nephritis and renal granulomas. In
      addition to interstitial edema with eosinophils and lymphocytes, her renal biopsy
      showed interstitial granulomas, immune complexes within tubular basement
      membranes, and the unusual feature of multinucleated giant cells engulfing
      tubules. Her acute renal failure resolved after the withdrawal of antibiotics and
      the initiation of intravenous steroid therapy.

PMID- 17039331
TI  - A confused child. Diagnosis: urinary tract infection, dilated urinary system and
      associated hyperammonaemic encephalopathy.

PMID- 17039332
TI  - Acute renal failure from xanthine nephropathy during management of acute
      leukemia.
AB  - Tumor lysis syndrome is a potentially life-threatening complication of induction
      chemotherapy for treatment of lymphoproliferative malignancies. Serious
      complications of tumor lysis syndrome are rare with the preemptive use of
      allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric
      acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl
      as a complication of tumor lysis syndrome during the treatment of T-cell acute
      lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of
      uric acid synthesis via allopurinol which increases plasma and urinary xanthine
      and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor
      lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine
      phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be
      considered in patients who develop acute renal failure following aggressive
      chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine
      measurements for xanthine could aid in the diagnosis of patients with
      nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be
      reduced or discontinued if xanthine nephropathy is suspected.

PMID- 17039333
TI  - Does citrate prevent nephrocalcinosis in preterm neonates?
AB  - Nephrocalcinosis (NC) occurs frequently in preterm neonates. A high U
      calcium/citrate is one of the contributing factors to the development of NC. In
      stone-forming children and adults citrate supplementation is a successful
      preventive therapy. In this randomized controlled trial the effect of citrate
      therapy was studied on the development of NC in preterm neonates with a
      gestational age <32 weeks. Thirty-eight preterm neonates (mean gestational age
      29.8 weeks (SD 1.6), mean birth weight 1,300 g (SD 351) were treated with sodium
      citrate (0.52 mmol/kg/day in four doses) from day 8 of life until at term and 36
      preterm neonates (mean gestational age 29.6 weeks (SD 1.6), mean birth weight
      1,282 g (SD 256) were not treated. U-calcium, U-creatinine, U-citrate and U-pH
      were measured at day 7, 14, 21, 28 of life and at term. Renal ultrasonography
      (US) was performed at term. U-citrate/creatinine and U-pH were significantly
      higher and U-calcium/citrate was significantly lower in the citrate group at day
      14, 21 and 28 compared with the control group (P<0.05). Complications of citrate
      administration were not encountered, however the incidence of NC was not
      significantly different in the treated (34%) compared with the control group
      (44%), P=0.37. Preterm neonates treated with citrate in the first months of life
      have higher U-citrate/creatinine and lower U-calcium/citrate compared with
      controls. Sodium citrate therapy in a dosage of 0.52 mmol/kg/day is safe but does
      not prevent NC. Whether a higher dose or potassium citrate decreases the
      incidence of NC should be evaluated in further studies.

PMID- 17039334
TI  - The effect of aldosterone blockade in patients with Alport syndrome.
AB  - Recent studies indicate that adding the mineralocorticoid receptor antagonist
      spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI
      and angiotensin receptor blocker (ARB), which is known as a triple blockade,
      enhances the more beneficial effects on urinary protein excretion of patients
      with chronic kidney diseases. In this study, we explored the effects of SP on
      urinary protein excretion in patients with Alport syndrome featuring persistent
      proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and
      ARB (candesartan). Five patients with Alport syndrome were enrolled and SP
      treatment (25 mg/day) was started. At the start of SP administration, all
      patients showed good renal function and none of them suffered from hypertension.
      We decided to assess the effect of SP by determining the morning urinary
      protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR).
      After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and
      18 months, while EGFR did not change. The drop in systolic and diastolic blood
      pressure was statistically significant and serum potassium level was slightly
      elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l).
      These results suggest that aldosterone receptor blockade combined with ACEI and
      ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria
      in patients with Alport syndrome as in those with other chronic kidney diseases.
      SP can thus be expected to constitute a good renoprotective agent for Alport
      syndrome. These preliminary data indicate that large-scale trials of this therapy
      should be done.

PMID- 17039335
TI  - [Introduction to the topic: blood really is a very special fluid!].

PMID- 17039337
TI  - [Anxiety and depression after loss of a lower limb].
AB  - A good number of psychosocial-, disease-, and disability-related variables
      influence the adaptation process after the loss of a lower limb. In this case
      psychological problems, as a result of a failed adaptation process, are common.
      Of the 75 patients examined who had an amputation of a lower extremity 27% showed
      increased depression and 25% increased anxiety scores; 18.3% showed higher than
      normal scores in both categories. Regression analysis showed that in addition to
      pain reception poor acceptance of the prosthesis is an important predictive
      factor for the development of psychological disorders and diseases like anxiety
      and depression. Therefore, measures for psychological diagnostics and care should
      be initiated soon after the amputation to prevent psychological abnormalities.
      Here interdisciplinary management and cooperation of the professions involved in
      the care of the patient are recommended.

PMID- 17039336
TI  - [Insoles for the rheumatic foot. A clinical and pedobarographic analysis].
AB  - BACKGROUND: Insoles are regarded as an appropriate tool for the management of
      rheumatic foot disorders. However, a quality control for this purpose has not
      been established. In our study, the clinical effectiveness of insoles used in
      patients with rheumatic foot disorders was addressed. In addition, we sought to
      establish pedobarography as a means of quality control for orthotic management of
      the rheumatic foot. MATERIAL AND METHODS: Our study included 20 rheumatoid
      arthritis patients with painful rheumatic foot deformities who were provided with
      insoles. Clinical data were obtained by physical examination and a 100-mm pain
      scale. Pedobarography was performed using the novel pedar cable system with new
      and individually designed insoles and after a 6-month follow-up. A shoe-only
      trial served as control. The parameters maximum force, peak pressure, force-time
      integral, and average pressure were analyzed in anatomical regions and an
      individually defined overloaded forefoot region. RESULTS: Clinical improvement
      was significant after a 6-month follow-up in spite of a heterogeneous group of
      patients. However, our results could not confirm consistent changes in plantar
      pressure distribution. CONCLUSION: As a conclusion, further efforts are necessary
      to establish a quality control for orthotic management of the rheumatic foot.

PMID- 17039338
TI  - [Labial salivary gland biopsy in Sjogren's syndrome].
AB  - In the majority of cases, autoimmune sialadenitis is a feature of Sjogren's
      syndrome. This systemic autoimmune disease is, therefore, clinically
      characterised by sicca symptoms such as xerostomia and keratoconjunctivitis
      sicca. Since autoimmune sialadenitis affects major as well as minor salivary
      glands, histopathological examination is almost always carried out using labial
      salivary gland biopsies. A positive histopathological result is determined as a
      focal lymphocytic sialadenitis with at least one aggregate of 50 or more
      lymphocytes and histiocytes per 4 mm2 of salivary gland tissue. As one out of
      four objective findings, focus scoring belongs to the classification criteria for
      Sjogren's syndrome according to the American-European consensus group.

PMID- 17039339
TI  - Acute fracture of the os trigonum.
AB  - A 21-year-old man presented with ankle pain after a motor vehicle accident.
      Imaging revealed an acute fracture of the os trigonum in addition to multiple,
      other lower-extremity fractures. In this case, the fracture of the os trigonum
      was a result of a significant traumatic injury. Thus, the presence of this
      fracture in an acute setting should prompt a search for other associated
      fractures.

PMID- 17039340
TI  - Massive hemoperitoneum due to ruptured inferior phrenic artery pseudoaneurysm
      after blunt trauma.
AB  - There had been no previous reports of ruptured pseudoaneurysm of inferior phrenic
      artery shortly after blunt abdominal trauma. Traumatic arterial pseudoaneurysms
      are either iatrogenic or the result of penetrating injuries and one of the
      sequelae of trauma. Post-traumatic pseudoaneurysm develops at varying time
      intervals after the initial insult. To our knowledge, this is the first report of
      massive hemoperitoneum caused by ruptured inferior phrenic artery pseudoaneurysm
      after blunt trauma. Pseudoaneurysm of inferior phrenic artery in patient with
      diaphragm injury is potentially a life-threatening condition and requires urgent
      management. Diagnosis of ruptured inferior phrenic artery pseudoaneurysm is based
      on clinical assessment combined with radiological investigations. We report a
      case of ruptured left inferior phrenic artery pseudoaneurysm as one aspect of
      massive hemoperitoneum caused by blunt abdominal trauma.

PMID- 17039341
TI  - Case report: urinary retention secondary to a foreign body in the male urethra.
AB  - We report the case of a male patient who presented to the Emergency Department
      with urinary retention secondary to a suspected foreign object in his urethra. We
      review the diagnosis and management of self-inserted urethral foreign objects in
      men. Emergent treatment is necessary in patients with urethral foreign objects.
      Prompt radiologic studies should be obtained because immediate bladder access and
      drainage is mandatory, especially in patients presenting with urosepsis or
      urinary retention. Endoscopic removal is the management of choice.

PMID- 17039342
TI  - A novel multiple-trauma CT-scanning protocol using patient repositioning.
AB  - Emergency CT examination is considered to be a trade-off between a short scan
      time and the acceptance of artifacts. This study evaluates the influence of
      patient repositioning on artifacts and scan time. Eighty-three consecutive
      multiple-trauma patients were included in this prospective study. Patients were
      examined without repositioning (group 1, n=39) or with patient rotation to feet
      first with arms raised for scanning the chest and abdomen/pelvis (group 2, n=44).
      The mean scan time was 21 min in group 1 and 25 min in group 2 (P=0.01). The mean
      repositioning time in group 2 was 8 min. Significantly, more artifacts were
      observed in group 1 (with a repeated scan in 7%) than in group 2 (P=0.0001). This
      novel multiple- trauma CT-scanning protocol with patient repositioning achieves a
      higher image quality with significantly fewer artifacts than without
      repositioning but increases scan time slightly.

PMID- 17039343
TI  - Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.
AB  - Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in
      single-layered epithelia of the gastrointestinal tract. Transgenic mice over
      expressing human KRT8 display pancreatic mononuclear infiltration, interstitial
      fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic
      insufficiency. These experimental data are in accordance with a recent report
      describing an association between KRT8 variations and chronic pancreatitis. This
      prompted us to investigate KRT8 polymorphisms in patients with pancreatic
      disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of
      patients with acute and chronic pancreatitis of various aetiologies or pancreatic
      cancer originating from Austria (n=16), the Czech Republic (n=90), Germany
      (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands
      (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied
      4,234 control subjects from these countries and 1,492 control subjects
      originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms
      were analysed by melting curve analysis with fluorescence resonance energy
      transfer probes. The frequency of G62C did not differ between patients with acute
      or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The
      frequency of G62C varied in European populations from 0.4 to 3.8%, showing a
      northwest to southeast decline. The Y54H alteration was not detected in any of
      the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control
      subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects
      of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do
      not predispose patients to the development of pancreatitis or pancreatic cancer.

PMID- 17039345
TI  - Aromatized arborane/fernane hydrocarbons as biomarkers for cordaites.
AB  - Previous palaeobotanical and palynological studies on coals from Euramerican
      Pennsylvanian ( identical with Late Carboniferous) coal basins indicate a major
      change in coal-swamp floras, especially at the Westphalian-Stephanian (
      approximately Kasimovian-Gzhelian, according to Geological Time Scale 2004)
      boundary. A flora dominated by arborescent lycophytes was replaced by a
      vegetation dominated by marattialean tree ferns in various Euramerican coal
      basins. Earlier combined palynological and organic geochemical studies on
      Westphalian/Stephanian coals and shales from the Saar-Nahe Basin (Germany)
      revealed that the distribution of aromatized arborane/fernane hydrocarbons in
      solvent extracts reflects the increasing importance of seed plants, especially
      cordaites (extinct group of gymnosperms), conifers and pteridosperms. However,
      the biological source of the precursor molecules could not be specified. To
      clarify if the arborane/fernane derivatives MATH, MAPH, DAPH 1, and DAPH 2 in
      Westphalian/Stephanian coals can be assigned to one of the three potential source
      plant groups, we analyzed coals, sediments and fossil plant remains from
      different Euramerican locations with respect to their biomarker composition and
      stable carbon isotopic composition. Thereby, stable carbon isotopic ratios showed
      only insignificant variations between Westphalian and Stephanian samples and
      proved to be an unsuitable tool to describe floral changes during the
      Westphalian/Stephanian of the Saar-Nahe Basin. In contrast, we were able to show
      for the first time that MATH, MAPH, DAPH 1 and DAPH 2 are prominent constituents
      only in extracts of cordaitean macrofossils and can therefore be regarded as
      biomarkers for this group of gymnosperms.

PMID- 17039344
TI  - Cold-loving microbes, plants, and animals--fundamental and applied aspects.
AB  - Microorganisms, plants, and animals have successfully colonized cold
      environments, which represent the majority of the biosphere on Earth. They have
      evolved special mechanisms to overcome the life-endangering influence of low
      temperature and to survive freezing. Cold adaptation includes a complex range of
      structural and functional adaptations at the level of all cellular constituents,
      such as membranes, proteins, metabolic activity, and mechanisms to avoid the
      destructive effect of intracellular ice formation. These strategies offer
      multiple biotechnological applications of cold-adapted organisms and/or their
      products in various fields. In this review, we describe the mechanisms of
      microorganisms, plants, and animals to cope with the cold and the resulting
      biotechnological perspectives.

PMID- 17039346
TI  - Fine mapping of the clubroot resistance gene, Crr3, in Brassica rapa.
AB  - A linkage map of Chinese cabbage (Brassica rapa) was constructed to localize the
      clubroot resistance (CR) gene, Crr3. Quantitative trait loci analysis using an
      F(3) population revealed a sharp peak in the logarithm of odds score around the
      sequence-tagged site (STS) marker, OPC11-2S. Therefore, this region contained
      Crr3. Nucleotide sequences of OPC11-2S and its proximal markers showed homology
      to sequences in the top arm of Arabidopsis chromosome 3, suggesting a synteny
      between the two species. For fine mapping of Crr3, a number of STS markers were
      developed based on genomic information from Arabidopsis. We obtained
      polymorphisms in 23 Arabidopsis-derived STS markers, 11 of which were closely
      linked to Crr3. The precise position of Crr3 was determined using a population of
      888 F(2) plants. Eighty plants showing recombination around Crr3 locus were
      selected and used for the mapping. A fine map of 4.74 cM was obtained, in which
      two markers (BrSTS-41 and BrSTS-44) and three markers (OPC11-2S, BrSTS-54 and
      BrSTS-61) were cosegregated. Marker genotypes of the 21 selected F(2) families
      and CR tests of their progenies strongly suggested that the Crr3 gene is located
      in a 0.35 cM segment between the two markers, BrSTS-33 and BrSTS-78.

PMID- 17039347
TI  - Vascular depression in older people with diabetes.
AB  - AIMS/HYPOTHESIS: Cerebrovascular disease may be causal or a vulnerability factor
      in late-onset depression and may explain the high rate of depression in older
      adults with diabetes. We explored a wide range of potential explanatory variables
      of depression in a longitudinal study of older diabetic subjects to investigate
      the vascular depression hypothesis in these patients. METHODS: We recruited 207
      subjects with diabetes selected for potential cognitive deficits from an existing
      observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an
      assessment of depression using a standardised diagnostic instrument (Cambridge
      Examination for Mental Disorders of the Elderly -- Revised). All subjects
      underwent a detailed clinical assessment at baseline and at follow-up (after 7.5
      +/- 1.1 years). RESULTS: Major depression was present in 45 subjects (21.7%) and
      minor depression in ten (4.8%). A positive history of strokes and the presence of
      peripheral arterial disease were significantly associated with depression at the
      time of diagnosis. In a subsample of 93 cases who underwent structural
      neuroimaging, the presence of cerebral infarcts was also significantly associated
      with depression. Treatment with glucose-lowering therapy, higher serum
      cholesterol levels and difficulties with activities of daily living at baseline
      were significant predictors of depression at follow-up.
      CONCLUSIONS/INTERPRETATION: A history of cerebrovascular disease was strongly
      associated with depression and cerebrovascular risk factors were significant
      predictors of depression in older diabetic patients. Our findings are consistent
      with the hypothesis that the excess risk of depression in older diabetic patients
      is related to underlying cerebrovascular disease.

PMID- 17039348
TI  - Noninvasive assessment of cardiac output using thoracic electrical bioimpedance
      in hemodynamically stable and unstable patients after cardiac surgery: a
      comparison with pulmonary artery thermodilution.
AB  - OBJECTIVE: To compare noninvasive cardiac output (CO)measurement obtained with a
      new thoracic electrical bioimpedance (TEB) device, using a proprietary
      modification of the impedance equation, with invasive measurement obtained via
      pulmonary artery thermodilution. DESIGN: Prospective, observational study.
      SETTING: Surgical intensive care unit (ICU) of a university-affiliated community
      hospital. PATIENTS AND PARTICIPANTS: Seventy-four adult patients undergoing
      elective cardiac surgery with routine pulmonary artery catheter placement.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Simultaneous paired CO and cardiac
      index (CI) measurements by TEB and thermodilution were obtained in mechanically
      ventilated patients upon admission to the ICU. For analysis of CI data the
      patients were subdivided into a hemodynamically stable group and a
      hemodynamically unstable group. The groups were analyzed using linear regression
      and tests of bias and precision. We found a significant correlation between
      thermodilution and TEB (r = 0.83; n < 0.001), accompanied by a bias of -0.01
      l/min/m(2) and a precision of +/-0.57 l/min/m(2) for all CI data pairs.
      Correlation, bias, and precision were not influenced by stratification of the
      data. The correlation coefficient, bias, and precision for CI were 0.86 (n<
      0.001), 0.03 l/min/m(2), and +/-0.47 l/min/m(2) in hemodynamically stable
      patients and 0.79 (n< 0.001), 0.06 l/min/m(2), and +/-0.68 l/min/m(2) in
      hemodynamically unstable patients. CONCLUSIONS: Our results demonstrate a close
      correlation and clinically acceptable agreement and precision between CO
      measurements obtained with impedance cardiography using a new algorithm to
      calculate CO from variations in TEB, and those obtained with the clinical
      standard of care, pulmonary artery thermodilution, in hemodynamically stable and
      unstable patients after cardiac surgery.

PMID- 17039350
TI  - Comment on "antibacterial-coated tracheal tubes cleaned with a Mucus Shaver" by
      Berra et al.

PMID- 17039351
TI  - Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator
      associated pneumonia.
AB  - OBJECTIVE: We conducted a prospective, open-label study to determine the steady
      state serum and epithelial lining fluid (ELF) concentrations of unbound ertapenem
      administered once daily to critically ill patients with early-onset ventilator
      associated pneumonia (VAP). DESIGN AND SETTING: Prospective, open-label study in
      an intensive care unit and research ward in a university hospital. PATIENTS:
      Fifteen patients with VAP received 1-h intravenous infusions of 1 g ertapenem
      once daily. INTERVENTIONS: After 2 days of therapy the steady-state serum and ELF
      concentrations of free ertapenem were determined by high-performance liquid
      chromatography. MEASUREMENTS AND RESULTS: The median (interquartile range) free
      ertapenem peak (C(max)), intermediate (C(12)), and trough (C(min)) concentrations
      (mg/l) 1, 12, and 24 h after the end of infusion were 30.3 (27.1-37.8), 4.8 (3.9
      6.4), and 0.8 (0.5-1.2) in serum and 9.4 (8.0-10.7), 2.0 (1.1-2.5), and 0.3 (0.2
      0.4) in ELF, respectively, showing a median free ertapenem percentage penetration
      in ELF of approx. 30%. The median (interquartile range) serum area under
      concentration-time curve of free ertapenem during the observational period was
      226.7 mg h(-1) l(-1) (202.2-263.9). CONCLUSION: Our study shows satisfactory
      results, with unbound ertapenem concentrations both in serum and ELF exceeding
      the MIC(90) values of most of the causative pathogens encountered in early-onset
      VAP during 50-100% time. This suggests that 1 g intravenous ertapenem
      administered once daily should be effective during the treatment of early-onset
      VAP in critically ill patients with no known risk factors for multidrug-resistant
      pathogens.

PMID- 17039353
TI  - Comment on "the Lund Concept for the treatment of severe head trauma
      physiological principles and clinical application".

PMID- 17039354
TI  - Non-invasive ventilation in chronic obstructive pulmonary disease patients:
      helmet versus facial mask.
AB  - RATIONALE: The helmet is a new interface with the potential of increasing the
      success rate of non-invasive ventilation by improving tolerance. OBJECTIVES: To
      perform a physiological comparison between the helmet and the conventional facial
      mask in delivering non-invasive ventilation in hypercapnic patients with chronic
      obstructive pulmonary disease. METHODS: Prospective, controlled, randomized study
      with cross-over design. In 10 patients we evaluated gas exchange, inspiratory
      effort, patient-ventilator synchrony and patient tolerance after 30 min of non
      invasive ventilation delivered either by helmet or facial mask; both trials were
      preceded by periods of spontaneous unassisted breathing. MEASUREMENTS: Arterial
      blood gases, inspiratory effort, duration of diaphragm contraction and ventilator
      assistance, effort-to-support delays (at the beginning and at the end of
      inspiration), number of ineffective efforts, and patient comfort. MAIN RESULTS:
      Non-invasive ventilation improved gas exchange (p<0.05) and inspiratory effort
      (p<0.01) with both interfaces. The helmet, however, was less efficient than the
      mask in reducing inspiratory effort (p<0.05) and worsened the patient-ventilator
      synchrony, as indicated by the longer delays to trigger on (p<0.05) and cycle off
      (p<0.05) the mechanical assistance and by the number of ineffective efforts
      (p<0.005). Patient comfort was no different with the two interfaces. CONCLUSIONS:
      Helmet and facial mask were equally tolerated and both were effective in
      ameliorating gas exchange and decreasing inspiratory effort. The helmet, however,
      was less efficient in decreasing inspiratory effort and worsened the patient
      ventilator interaction.

PMID- 17039355
TI  - The pharmacological effects of ozone on isolated guinea pig tracheal
      preparations.
AB  - Ozone is a potent oxidizing agent with a variety of potential uses, including its
      antimicrobial and deodorising properties. The recent increased use of ozone led
      to questions regarding its safety in humans. This study specifically focussed on
      the in vitro effect of ozone on isolated guinea pig tracheal tissue as well as
      its effect on the isolated trachea in the presence of various drugs with well
      known effects, including methacholine and isoproterenol. The results found in
      this study identified two direct effects on the isolated trachea due to ozone
      exposure: (1) a definite contraction of the isolated trachea immediately after
      exposure to ozone, and (2) a clearly visible and significant hyper responsiveness
      of the isolated trachea to irritants, e.g. methacholine. Although ozone has a
      negative effect on the trachea, it was concluded that ozone has no adverse effect
      on muscarinic receptors. We found that ozone has a significant desensitizing
      effect on the pharmacological response of beta sympathomimetics (isoproterenol),
      while isoproterenol itself has a relaxing effect on the ozone-induced contraction
      of the isolated trachea. Observations in this in vitro study further emphasised
      that ozone does have a negative effect on respiratory health. It is underlined
      that the inhalation of ozone should be avoided by workers who are often in
      contact with the gas, and especially by those with existing airway diseases. An
      apparent EC(50) value of ozone on the trachea was established by two different
      methods as 5.71 and 9.78 x 10(-3 )M, respectively.

PMID- 17039356
TI  - Comparative effects of selective and non-selective nitric oxide synthase
      inhibition in gentamicin-induced rat nephrotoxicity.
AB  - Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some
      studies provided evidences that increased endothelial NOS (eNOS) activity leads
      to restoration of renal function after injury, but activation of inducible NOS
      (iNOS) aggravates renal failure. In the present study, the beneficial effects of
      selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been
      investigated. Four groups of rats were studied. Untreated control rats received
      saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats
      received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor)
      simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were
      administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were
      treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose
      (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(
      1)) were administered 2 and 4 h after GM. In all groups, serum and urine
      creatinine levels were measured. Creatinine clearance was calculated and
      considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b
      D-glucose aminidase (NAG) activities were also determined. After experiments,
      kidney sections were histologically studied. Selective iNOS inhibition by L-NIL
      prevented the GM-induced decrease in GFR and increase in creatinine levels, while
      complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction,
      elevation of creatinine levels and enzyme release (P < 0.05). Histological
      studies showed that GM-treated kidneys had evidences of tubular damages and these
      damages were less evident by the administration of L-NIL. In conclusion,
      selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non
      selective inhibition of NOS aggravates it.

PMID- 17039357
TI  - Adaptation of postural orientation to changes in surface inclination.
AB  - We previously showed that standing on an inclined surface resulted in an after
      effect of leaning in many healthy, blindfolded subjects when they returned to
      standing on a horizontal surface (Kluzik et al. in Exp Brain Res 162:474-489,
      2005). The direction of leaning depended on the direction of prior surface
      inclination, always in a direction that preserved the relative alignment between
      the body and the support surface. For example, subjects leaned forward after they
      stood on a toes-up-inclined surface. In the present study, we investigated how
      the amplitude of surface inclination affected postural muscle activity, joint
      position, body segment orientation, and body center of mass (CoM) and foot center
      of pressure (CoP) locations before, during, and after subjects stood on an
      inclined surface. We asked whether the mechanism that underlies the lean after
      effect involves regulation of local postural variables, such as the position of
      the ankle joint or the level of muscle activity, or whether instead, the
      mechanism involves regulation of global, whole-body postural variables that can
      only be determined by multisensory processing, such as orientation of the trunk
      or the body's CoM. In one experiment, we found that varying the amplitude of a
      toes-up surface inclination between 2.5 degrees and 10 degrees had a systematic,
      linear, effect on the post-incline orientation of the trunk and head, but did not
      systematically affect the post-incline orientation of the legs, position of the
      ankle joint, the level of EMG activity, or the location of the CoP. In a second
      experiment, we found that preventing the legs from leaning in the post-incline
      period did not abolish leaning of the upper body. These findings suggest that (1)
      the body-to-support-surface relationship is an important reference for the CNS
      internal representation of postural orientation which is subject to adaptive
      modification and (2) the adaptive mechanism underlying the post-incline after
      effect of leaning acts at the level of global, whole-body postural variables.

PMID- 17039358
TI  - Fatigue-induced adaptive changes of anticipatory postural adjustments.
AB  - To examine the fatigue-induced adaptive changes (e.g., timing) of anticipatory
      postural adjustments (APAs), APAs of 30 research participants were recorded
      before (baseline) and after (post-test) conditions of either rest (control group,
      n=15) or fatigue (fatigue group, n=15). Muscle fatigue was generated using a dead
      lift exercise performed to exhaustion. Self-initiated postural perturbations were
      induced using a rapid unilateral arm-raising maneuver (focal movement), and APAs
      were obtained using electromyography (EMG) recorded bilaterally in the lumbar and
      thoracic paraspinal muscles as well as the hamstring muscles. Postural stability
      during the focal movement was assessed using a force plate. Results showed that
      fatigue had no effect on postural stability during the focal movement, and yet
      caused earlier APA onsets in three of the six muscles evaluated. In spite of
      early APA activation, the APA EMG integrals of two of the three postural control
      muscles which exhibited fatigue-induced early APA onsets (T9 and L4 contralateral
      paraspinals) did not differ between baseline and post-test measures. The findings
      suggest that early APA onset may enhance postural stability by permitting a
      longer duration APA which can counteract fatigue-induced decreases in the force
      producing capability of muscles that contribute to postural stability.

PMID- 17039360
TI  - Two new Ig VH gene families in Oncorhynchus mykiss.
AB  - Genes encoding the immunoglobulin heavy-chain variable region (Ig VH) in rainbow
      trout (Oncorhynchus mykiss) have been grouped into 11 families. While obtaining a
      baseline assessment of the various gene families utilized by trout in the
      production of secreted antibody, we discovered two new families. These proposed
      Ig VH families, Families XII and XIII, were rarely observed; only two VH sequence
      types were detected for each new family, suggesting that they may not be commonly
      used in response to antigens, or that the captive environment may not lead to
      typical exposures seen in the wild. Additionally, unlike preceding studies, we
      found at least one representative gene sequence for each of the 11 reported Ig VH
      gene families, possibly indicating that the repertoire of trout Ig VH gene
      families may be more universal among different stocks than previously realized.

PMID- 17039359
TI  - PEG as a tool to gain insight into membrane fusion.
AB  - Thirty years ago, Klaus Arnold and others showed that the action of PEG in
      promoting cell-cell fusion was not due to such effects as surface absorption,
      cross-linking, solubilization, etc. Instead PEG acted simply by volume exclusion,
      resulting in an osmotic force driving membranes into close contact in a
      dehydrated region. This simple observation, based on a number of physical
      measurements and the use of PEG-based detergents that insert into membranes,
      spawned several important areas of research. One such area is the use of PEG to
      bring membranes into contact so that the role of different lipids and fusion
      proteins in membrane fusion can be examined in detail. We have summarized here
      insights into the fusion mechanism that have been obtained by this approach. This
      evidence indicates that fusion of model membranes (and probably cell membranes)
      occurs via severely bent lipidic structures formed at the point of sufficiently
      close contact between membranes of appropriate lipid composition. This line of
      research has also suggested that fusion proteins seem to catalyze fusion in part
      by reducing the free energy of hydrophobic interstices inherent to the lipidic
      fusion intermediate structures.

PMID- 17039362
TI  - Adrenal Castleman's disease.

PMID- 17039361
TI  - Characterization of swine leukocyte antigen polymorphism by sequence-based and
      PCR-SSP methods in Meishan pigs.
AB  - Resource herds of swine leukocyte antigen (SLA)-characterized pigs are an
      important tool for the study of immune responses, disease resistance, and
      production traits. They are also valuable large animal models for biomedical
      research, such as transplantation. The Meishan breed of pig is an economically
      significant breed that is available at several research institutions in the
      United States. We have characterized the SLA polymorphism of the breeding stock
      in the herd maintained at the University of Illinois and developed a simple assay
      to SLA type individuals within that herd. We have used a reverse transcription
      polymerase chain reaction (RT-PCR)-based SLA typing method to clone and DNA
      sequence 19 SLA alleles at three SLA class Ia (SLA-1, SLA-2, and SLA-3) and two
      SLA class II (SLA-DRB1 and SLA-DQB1) loci. Based on this sequence information, a
      rapid SLA typing assay was developed to discriminate each allele using PCR with
      sequence-specific primers (PCR-SSP). Using this method, we were able to
      characterize the entire Meishan breeding stock and identify four SLA haplotypes
      present in the herd. The combination of SLA typing by cloning and DNA sequencing
      with PCR-SSP is therefore a valuable tool for the characterization of SLA alleles
      and haplotypes in resource herds of pigs.

PMID- 17039363
TI  - Use of ziprasidone in patients with fibromyalgia: a case series.
AB  - Atypical antipsychotics may be useful in chronic pain treatment. The objective of
      the present study was to assess the effect of ziprasidone in fibromyalgia
      management. Ziprasidone was administered to 32 fibromyalgia patients at a dose of
      20 mg/day, subsequently adjusted according to clinical response and tolerability.
      Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), a
      Clinical Global Impression improvement scale (CGIi), and a scale evaluating the
      severity of fibromyalgia symptoms were administered at 4 week intervals for 12
      weeks. Drug adverse reactions were recorded. Ten patients withdrew from the
      study. The CGIi showed 32% of responders. FIQ and PSQI scores showed a non
      statistically significant decrease. The conditions of stiffness, anxiety and
      sadness improved significantly. Most frequent side effects included sleep
      disturbances, headache, tremor, and rigidity. Although ziprasidone does not seem
      an especially useful adjunct drug in fibromyalgia, it could be tried on patients
      who are markedly anxious and/or depressed.

PMID- 17039364
TI  - CT urography: a comparison of strategies for upper urinary tract opacification.
AB  - A consensus is yet to be reached regarding the best strategy for ensuring maximum
      ureteric delineation during CT urography (CTU). In this study we have compared
      various CTU protocols to try to establish the best method for ureteric
      delineation. Saline infusion in the supine position, saline infusion in the prone
      position, furosemide administration (10 mg, iv) and buscopan administration (20
      mg iv) with saline infusion in the prone position were tried in four groups, each
      having 15 patients who were undergoing CTU. The pelvicalyceal system and ureter
      were divided into six segments, to each of which an opacification score was
      assigned (0, unopacified segment; 1, less than 50% opacified segment; 2, 50-99%
      of the segment opacified; or 3, completely opacified segment) and the results
      compared. Furosemide administration resulted in complete opacification of 93% of
      the ureters (28 of 30). In the distal (below the sciatic notch) ureter, the mean
      score with furosemide was 2.9, while that with saline, supine and prone
      positioning was 1.87 and 1.83, respectively, and this difference was highly
      significant (P = 0.0002 and P = 0.0001). It was also significantly higher than
      the buscopan group (score 2.3, P = 0.002). Also in the lower (the iliac crest to
      the sciatic notch) and upper (above the iliac crest) ureter, furosemide had
      significantly higher scores than saline infusion in either position. Saline
      infusion in the supine and prone positions had very similar scores in all
      segments that were less than the buscopan group, but this difference was not
      statistically significant. During CT urography, furosemide administration in low
      doses is the most effective and convenient technique for ureteric opacification.

PMID- 17039365
TI  - Association of left renal vein variations and pelvic varices in abdominal MDCT.
AB  - The aim of this study was to determine whether left renal vein (LRV) variation is
      associated with pelvic varices and left ovarian vein (LOV) reflux. Routine
      abdominal multidetector-row computed tomography scans of 324 women without
      symptoms of pelvic congestion syndrome were analyzed. Presence and type of LRV
      variants (circumaortic [CLRV] or retroaortic [RLRV]) were recorded. Diameters of
      the LRV, ovarian veins (OVs), and parauterine veins were measured and a specific
      LRV diameter ratio was calculated for each patient. Presence and severity of
      pelvic varices and LOV reflux were noted. Pelvic varices were detected in 59
      (18%) of the total of 324 women, in 7 (37%) of the 19 women with RLRVs, in 7
      (29%) of the 24 women with CLRVs, and in 45 (16%) of the 281 women with normal
      LRVs. The frequency of pelvic varices in the women with LRV variation was
      significantly higher than that in the group with normal LRV anatomy (33 vs. 16%;
      p=0.009). The frequency of pelvic varices in the women with RLRVs was also
      significantly higher than that in the group with normal LRV anatomy (p=0.02). LRV
      diameter ratio was correlated with presence of pelvic varices and presence of LOV
      reflux (p=0.0001 for both). This study revealed an association between pelvic
      varices and LRV variations in a population of predominantly multiparous women.

PMID- 17039366
TI  - Exercise training effects on premenstrual distress and ovarian steroid hormones.
AB  - Preliminary studies suggest that moderate physical activity may reduce both
      premenstrual distress (PD) and the ovarian steroid hormones, progesterone and
      estradiol, which have been implicated in PD. We attempted to replicate these
      findings, while exploring possible relationships between hormone levels and PD.
      In a cross-sectional study, 20 moderate exercisers and 34 sedentary women
      completed PD symptom questionnaires and collected urine samples, daily,
      throughout a complete menstrual cycle. PD was calculated as the difference in
      symptom scores reported during the average of the 4 days prior to menses and the
      average of the 4 days closest to mid-cycle. Urine samples taken from the last
      quarter of the menstrual cycle were analyzed for urinary estrone glucoronide
      (E1G) and pregnanediol glucoronide. In a prospective study the same measures were
      used with 14 sedentary women before and after a 24-week moderate exercise
      training program. In the cross-sectional study, exercising women reported lower
      Pain symptoms, and had lower peak E1G levels than did sedentary women. The
      baseline PD symptoms loneliness, crying, and skin blemishes with were
      statistically significantly and positively correlated with pregnanediol
      glucoronide levels in the cross-sectional study. In the prospective study,
      exercise reduced the global PD symptom score, including the Water Retention and
      Pain scales, and reduced pregnanediol glucoronide and peak E1G levels. Moderate
      aerobic exercise may lessen both PD symptoms and late luteal phase ovarian
      hormone levels. An exercise program may benefit women with progesterone-related
      premenstrual affect disturbance.

PMID- 17039368
TI  - Molecular and biochemical characterization of two brassinosteroid
      sulfotransferases from Arabidopsis, AtST4a (At2g14920) and AtST1 (At2g03760).
AB  - Mammalian sulfotransferases (EC 2.8.2) are involved in many important facets of
      steroid hormone activity and metabolism. In this study, Arabidopsis AtST4a and
      AtST1 were identified and characterized as brassinosteroid sulfotransferases that
      appear to be involved in different aspects of hormone regulation. The two
      proteins share 44% identity in amino acid sequence, and belong to different plant
      sulfotransferase families. AtST4a was specific for biologically active end
      products of the brassinosteroid pathway. The enzyme sulfated brassinosteroids
      with diverse side-chain structures, including 24-epibrassinosteroids and the
      naturally occurring (22R, 23R)-28-homobrassinosteroids. AtST4a belongs to a small
      subfamily of sulfotransferases having two other members, AtST4b and -c. Among the
      three recombinant enzymes, only AtST4a was catalytically active with
      brassinosteroids. Transcript expression of AtST4 subfamily members was largely
      specific to the root. AtST4b- and -c transcript levels were induced by treatment
      with trans-zeatin, while AtST4a was repressed under the same conditions,
      supporting a divergent function of AtST4a. Co-regulation of AtST4b and -c
      correlated with their location in tandem on chromosome 1. AtST1 was
      stereospecific for 24-epibrassinosteroids, with a substrate preference for the
      metabolic precursor 24-epicathasterone, and exhibited catalytic activity with
      hydroxysteroids and estrogens. To gain more insight into this dual activity with
      plant and mammalian steroids, enzymatic activities of human steroid
      sulfotransferases toward brassinosteroids were characterized. The
      dehydroepiandrosterone sulfotransferase SULT2A1 displayed catalytic activity with
      a selected set of 24-epibrassinolide precursors, including 24-epicathasterone,
      with specific activities comparable to that measured for the endogenous substrate
      dehydroepiandrosterone. The comparable activity profiles of AtST1 and SULT2A1
      suggest a similar architecture of the acceptor-binding site between the two
      enzymes, and may potentially reflect a common ability to conjugate certain
      xenobiotics.

PMID- 17039369
TI  - Accumulation of multiple-repeat starch-binding domains (SBD2-SBD5) does not
      reduce amylose content of potato starch granules.
AB  - This study investigates whether it is possible to produce an amylose-free potato
      starch by displacing the amylose enzyme, granule-bound starch synthase I (GBSSI),
      from the starch granule by engineered, high-affinity, multiple-repeat family 20
      starch-binding domains (SBD2, SBD3, SBD4, and SBD5). The constructs were
      introduced in the amylose-containing potato cultivar (cv. Kardal), and the
      starches of the resulting transformants were compared with those of SBD2
      expressing amylose-free (amf) potato clones. It is shown that a correctly sized
      protein accumulated in the starch granules of the various transformants. The
      amount of SBD accumulated in starch increased progressively from SBD to SBD3;
      however, it seemed as if less SBD4 and SBD5 was accumulated. A reduction in
      amylose content was not achieved in any of the transformants. However, it is
      shown that SBDn expression can affect physical processes underlying granule
      assembly, in both genetic potato backgrounds, without altering the primary
      structure of the constituent starch polymers and the granule melting temperature.
      Granule size distribution of the starches obtained from transgenic Kardal plants
      were similar to those from untransformed controls, irrespective of the amount of
      SBDn accumulated. In the amf background, granule size is severely affected. In
      both the Kardal and amf background, apparently normal oval-shaped starch granules
      were composed of multiple smaller ones, as evidenced from the many "Maltese
      crosses" within these granules. The results are discussed in terms of different
      binding modes of SBD.

PMID- 17039367
TI  - The peroxisomal ABC transporter family.
AB  - This review describes the current state of knowledge about the ABCD family of
      peroxisomal half adenosine-triphosphate-binding cassette (ABC) transporters.
      ABCDs are predicted to be present in a variety of eukaryotic organisms, although
      at present, only ABCDs in the yeast Saccharomyces cerevisiae, the plant
      Arabidopsis thaliana, and different mammalian species have been identified and
      characterized to any significant extent. The functional role of none of these
      ABCDs has been established definitively and awaits successful reconstitution of
      ABCDs, either as homo- or heterodimers into liposomes, followed by transport
      studies. Data obtained in S. cerevisiae suggest that the two ABCDs, which have
      been identified in this organism, form a heterodimer, which actually transports
      acyl coenzyme A esters across the peroxisomal membrane. In mammals, four ABCDs
      have been identified, of which one [adrenoleukodystrophy protein (ALDP)] has been
      implicated in the transport of the coenzyme A esters of very-long-chain fatty
      acids. Mutations in the gene (ABCD1) encoding ALDP are the cause of a severe X
      linked disease, called X-linked adrenoleukodystrophy. The availability of mutant
      mice in which Abcd1, Abcd2, or Abcd3 have been disrupted will help to resolve the
      true role of the peroxisomal half-ABC transporters.

PMID- 17039370
TI  - Inhibition of lycopene cyclase results in accumulation of chlorophyll precursors.
AB  - Free porphyrins and their magnesium complexes, including chlorophylls, are potent
      photo-sensitizers. Plants usually accumulate these compounds bound to proteins
      together with protective compounds like carotenoids. Besides their protective
      role, carotenoids can play a structural role in these complexes. To analyze the
      effect of impaired carotenogenesis on plastid membranes we applied to barley
      seedlings the bleaching herbicide 2-(4-chlorophenylthio)triethylamine (CPTA) as a
      specific inhibitor for the cyclization of lycopene. To avoid interference with
      photo-oxidation, the essential experiments were performed on seedlings grown in
      darkness. While the amount of total carotenoids decreased, we found accumulation
      of more 6-carotene than lycopene in darkness clearly showing that CPTA inhibits
      the lycopene beta-cyclase more effectively than the lycopene epsilon-cyclase. The
      CPTA treatment resulted in accumulation of non-photoactive protochlorophyllide a;
      the amount of photoactive protochlorophyllide and NADPH:protochlorophyllide
      oxidoreductase remained constant. Further, the level of Mg protophorphyrin and
      its monomethyl ester increased to an extent similar to that obtained by
      application of 5-aminolevulinic acid (ALA). The perturbation of the
      ultrastructure of etioplast inner membranes, observed after CPTA-treatment, was
      not found after ALA-treatment; this excluded the accumulated tetrapyrroles as
      responsible for the perturbation. By contrast, the down-regulation of Lhcb and
      RbcS genes found after CPTA-treatment was compatible with the presumed role of Mg
      protophorphyrin as "plastid signal" for regulation of nuclear gene expression.
      Possible mechanisms for enhancement of tetrapyrrole accumulation by non-cyclic
      carotenoids are discussed.

PMID- 17039372
TI  - The effects of ultraviolet radiation on photosynthetic performance, growth and
      sunscreen compounds in aeroterrestrial biofilm algae isolated from building
      facades.
AB  - The effects of artificial ultraviolet radiation [UVR; 8 W m(-2) ultraviolet-A
      (UVA), 0.4 W m(-2) ultraviolet-B (UVB)] on photosynthetic performance, growth and
      the capability to synthesise mycosporine-like amino acids (MAAs) was investigated
      in the aeroterrestrial green algae Stichococcus sp. and Chlorella luteoviridis
      forming biofilms on building facades, and compared with the responses of two
      green algae, from soil (Myrmecia incisa) and brackish water (Desmodesmus
      subspicatus). All species exhibited decreasing quantum efficiency (Fv/Fm) after 1
      3 days exposure to UVR. After 8-12 days treatment, however, all aeroterrestrial
      isolates exhibited full recovery under UVA and UVA/B. In contrast, D. subspicatus
      showed only 80% recovery after treatment with UVB. While Stichococcus sp. and C.
      luteoviridis exhibited a broad tolerance in growth under all radiation conditions
      tested, M. incisa showed a significant decrease in growth rate after exposure to
      UVA and UVA/B. Similarly D. subspicatus grew with a reduced rate under UVA, but
      UVA/B led to full inhibition. Using HPLC, an UV-absorbing MAA (324 nm-MAA) was
      identified in Stichococcus sp. and C. luteoviridis. While M. incisa contained a
      specific 322 nm-MAA, D. subspicatus lacked any trace of such compounds. UV
      exposure experiments indicated that all MAA-containing species are capable of
      synthesizing and accumulating these compounds, thus supporting their function as
      an UV-sunscreen. All data well explain the conspicuous ecological success of
      aeroterrestrial green algae in biofilms on facades. Biosynthesis and accumulation
      of MAAs under UVR seem to result in a reduced UV-sensitivity of growth and
      photosynthesis, which consequently may enhance survival in the environmentally
      harsh habitat.

PMID- 17039371
TI  - Secretion marker proteins and cell-wall polysaccharides move through different
      secretory pathways.
AB  - The building up of the cell wall is tightly dependent on the functionality of the
      secretory pathway. Syntaxins as well as other SNARE proteins play important roles
      during vesicle secretion and fusion. We have compared the secretion of newly
      synthesised cell-wall polysaccharides to that of secretory marker proteins such
      as secreted green-fluorescent protein (sec-GFP) and secreted rat preputial beta
      glucuronidase (secRGUS) in leaf protoplasts and roots of wild-type and transgenic
      Nicotiana tabacum plants, overexpressing a syntaxin homologue NtSyr1 (Sp1) and
      its soluble variant Sp2 that interferes specifically with Sp1 function, affecting
      post-Golgi transport. In protoplasts transiently transformed with secGFP and Sp1,
      no variation was observed in the pattern of fluorescence with respect to control;
      on the contrary, GFP fluorescence accumulate within the cells in protoplasts co
      transformed with secGFP and Sp2. Sp2 reduced the percentage of marker protein
      secretion to 53% as quantified with secRGUS. In protoplasts obtained from leaves
      of wild-type and transformed tobacco plants expressing Sp1, Sp2 and Sp1 plus Sp2,
      no remarkable differences in the percentage of newly synthesised polysaccharides
      incorporated into the regenerating cell walls were observed. The same results
      were confirmed in roots of whole transformed seedlings. Tests with cytochalasin D
      (CD) showed a marked decrease in the amount of newly synthesised polysaccharides
      into the wall and a simultaneous sharp increase in membrane-associated
      polysaccharides. SecRGUS secretion was also inhibited by CD. The data indicate
      that marker proteins and matrix polysaccharides, as well as cellulose synthase
      complexes, are secreted through the involvement of different secretory
      machineries.

PMID- 17039373
TI  - Plant native tryptophan synthase beta 1 gene is a non-antibiotic selection marker
      for plant transformation.
AB  - Gene transformation is an integral tool for plant genetic engineering. All
      antibiotic resistant genes currently employed are of bacterial origin and their
      presence in the field is undesirable. Therefore, we developed a novel and
      efficient plant native non-antibiotic selection system for the selection of
      transgenic plants in the model system Arabidopsis. This new system is based on
      the enhanced expression of Arabidopsis tryptophan synthase beta 1 (AtTSB1) and
      the use of 5-methyl-tryptophan (5MT, a tryptophan [Trp] analog) and/or CdCl2 as
      selection agent(s). We successfully integrated an expression cassette containing
      an AtT-SB1 cDNA driven by a cauliflower mosaic virus 35S promoter into
      Arabidopsis by floral dip transformation. Transgenic plants were efficiently
      selected on MS medium supplemented with 75 microM 5MT or 300 microM CdCl2 devoid
      of antibiotics. TSB1 selection was as efficient as the conventional hygromycin
      selection system. Northern blot analysis of transgenic plants selected by 5MT and
      CdCl2 revealed increased TSB1 mRNA transcript whereas uneven transcript levels of
      hygromycin phosphotransferase II (hpt) (control) was observed. Gas chromatography
      mass spectrometry revealed 10-15 fold greater free Trp content in AtT-SB1
      transgenic plants than in wild-type plants grown with or without 5MT or CdCl2.
      Taken together, the TSB1 system provides a novel selection system distinct from
      conventional antibiotic selection systems.

PMID- 17039374
TI  - Microchemical analysis of laser-microdissected stone cells of Norway spruce by
      cryogenic nuclear magnetic resonance spectroscopy.
AB  - Stone cells (sclereids) in Norway spruce (Picea abies) bark have been reported to
      be highly lignified tissues that are important in physical defence against bark
      beetle invasion. Microchemical analyses of the low-molecular weight compounds in
      the stone cells of Norway spruce were carried out using laser microdissection in
      combination with cryogenic nuclear magnetic resonance and mass spectrometry
      (LMD/NMR/MS). Two phenolic compounds, the stilbene astringin and the
      dihydroflavonol dihydroxyquercetin 3'-O-beta-D-glucopyranoside, were identified
      indicating that stone cells are more than just repositories for lignin. Both of
      these compounds were also found to be present in other phloem tissue at a higher
      level than in the stone cells based on quantification by cryogenic 1H NMR. Our
      results suggest that stone cells may be involved in chemical as well as physical
      defense against bark beetles and their associated microorganisms. This paper
      reports on the identification of secondary plant metabolites from a single laser
      microdissected population of plant cells offering a sensitive new way to
      determine the chemical profile of specific plant cell types with a high degree of
      precision.

PMID- 17039375
TI  - Myogenic progenitor cells in the mouse embryo are marked by the expression of
      Pax3/7 genes that regulate their survival and myogenic potential.
AB  - The transcription factors Pax3 and Pax7 are important regulators of myogenic cell
      fate, as demonstrated by genetic manipulations in the mouse embryo. Pax3 lies
      genetically upstream of MyoD and has also been shown recently to directly control
      Myf5 transcription in derivatives of the hypaxial somite, where it also plays an
      important role in ensuring cell survival. Both Pax3 and Pax7 are expressed in
      myogenic progenitor cells derived from the central dermomyotome that make a major
      contribution to skeletal muscle growth. In Pax3/Pax7 double mutants, the myogenic
      determination genes, Myf5 and MyoD, are not activated in these cells which become
      incorporated into other tissues or die. This again demonstrates the dual function
      of Pax factors in regulating the entry of progenitor cells into the myogenic
      programme and in ensuring their survival. Pax3 expression marks cells in the
      dermomyotome that either become myogenic or downregulate Pax3 and assume another
      cell fate. The latter include the smooth muscle cells of the dorsal aorta that
      share a common clonal origin with the skeletal muscle of the myotome, thus
      illustrating the initial multipotency of Pax3 expressing cells.

PMID- 17039376
TI  - Molecular characterization and genomic distribution of Isis: a new
      retrotransposon of Drosophila buzzatii.
AB  - A new transposable element, Isis, is identified as a LTR retrotransposon in
      Drosophila buzzatii. DNA sequence analysis shows that Isis contains three long
      ORFs similar to gag, pol and env genes of retroviruses. The ORF1 exhibits
      sequence homology to matrix, capsid and nucleocapsid gag proteins and ORF2
      encodes a putative protease (PR), a reverse transcriptase (RT), an Rnase H (RH)
      and an integrase (IN) region. The analysis of a putative env product, encoded by
      the env ORF3, shows a degenerated protein containing several stop codons. The
      molecular study of the putative proteins coded by this new element shows striking
      similarities to both Ulysses and Osvaldo elements, two LTR retrotransposons,
      present in D. virilis and D. buzzatii, respectively. Comparisons of the predicted
      Isis RT to several known retrotransposons show strong phylogenetic relationships
      to gypsy-like elements, particulary to Ulysses retrotransposon. Studies of Isis
      chromosomal distribution show a strong hybridization signal in centromeric and
      pericentromeric regions, and a scattered distribution along all chromosomal arms.
      The existence of insertional polymorphisms between different strains and high
      molecular weight bands by Southern blot suggests the existence of full-sized
      copies that have been active recently. The presence of euchromatic insertion
      sites coincident between Isis and Osvaldo could indicate preferential insertion
      sites of Osvaldo element into Isis sequence or vice versa. Moreover, the presence
      of Isis in different species of the buzzatii complex indicates the ancient origin
      of this element.

PMID- 17039377
TI  - Transcriptional analysis between two wheat near-isogenic lines contrasting in
      aluminum tolerance under aluminum stress.
AB  - To understand the mechanisms of aluminum (Al) tolerance in wheat (Triticum
      aestivum L.), suppression subtractive hybridization (SSH) libraries were
      constructed from Al-stressed roots of two near-isogenic lines (NILs). A total of
      1,065 putative genes from the SSH libraries was printed in a cDNA array. Relative
      expression levels of those genes were compared between two NILs at seven time
      points of Al stress from 15 min to 7 days. Fifty-seven genes were differentially
      expressed for at least one time point of Al treatment. Among them, 28 genes
      including genes for aluminum-activated malate transporter-1, ent-kaurenoic acid
      oxidase-1, beta-glucosidase, lectin, histidine kinase, and phospoenolpyruvate
      carboxylase showed more abundant transcripts in Chisholm-T and therefore may
      facilitate Al tolerance. In addition, a set of genes related to senescence and
      starvation of nitrogen, iron, and sulfur, such as copper chaperone homolog,
      nitrogen regulatory gene-2, yellow stripe-1, and methylthioribose kinase, was
      highly expressed in Chisholm-S under Al stress. The results suggest that Al
      tolerance may be co-regulated by multiple genes with diverse functions, and those
      genes abundantly expressed in Chisholm-T may play important roles in enhancing Al
      tolerance. The down-regulated genes in Chisholm-S may repress root growth and
      restrict uptake of essential nutrient elements, and lead to root senescence.

PMID- 17039379
TI  - Heat wave impacts on mortality in Shanghai, 1998 and 2003.
AB  - A variety of research has linked extreme heat to heightened levels of daily
      mortality and, not surprisingly, heat waves both in 1998 and in 2003 all led to
      elevated mortality in Shanghai, China. While the heat waves in the two years were
      similar in meteorological character, elevated mortality was much more pronounced
      during the 1998 event, but it remains unclear why the human response was so
      varied. In order to explain the differences in human mortality between the two
      years' heat waves, and to better understand how heat impacts human health, we
      examine a wide range of meteorological, pollution, and social variables in
      Shanghai during the summers (15 June to 15 September) of 1998 and 2003. Thus, the
      goal of this study is to determine what was responsible for the varying human
      health response during the two heat events. A multivariate analysis is used to
      investigate the relationships between mortality and heat wave intensity,
      duration, and timing within the summer season, along with levels of air
      pollution. It was found that for heat waves in both summers, mortality was
      strongly associated with the duration of the heat wave. In addition, while
      slightly higher than average, the air pollution levels for the two heat waves
      were similar and cannot fully explain the observed differences in human
      mortality. Finally, since the meteorological conditions and pollution levels for
      the two heat waves were alike, we conclude that improvements in living conditions
      in Shanghai, such as increased use of air conditioning, larger living areas, and
      increased urban green space, along with higher levels of heat awareness and the
      implementation of a heat warning system, were responsible for the lower levels of
      human mortality in 2003 compared to 1998.

PMID- 17039378
TI  - The Bradyrhizobium japonicum Fur protein is an iron-responsive regulator in vivo.
AB  - The Fur protein is a global regulator of iron metabolism in many bacterial
      species. However, Fur homologs from some rhizobia appear not to mediate iron
      dependent gene expression in vivo. Here, transcriptional profiling analysis
      showed that more than one-fourth of the genes within the iron stimulon of
      Bradyrhizobium japonicum were aberrantly controlled by iron in a fur mutant.
      However, Fur has only a modest role in regulating iron transport genes.
      Quantitative real time reverse transcriptase PCR measurements confirmed abnormal
      gene expression in iron-limited cells of the fur strain, thereby demonstrating
      that Fur must function under those conditions. The findings show that B.
      japonicum Fur is involved in iron-dependent gene expression, and support the
      conclusion that rhizobial Fur proteins have novel functions compared with well
      studied model systems.

PMID- 17039380
TI  - "Laying on of hands" improves well-being in patients with advanced cancer.
AB  - GOAL OF WORK: To determine whether the impact of "laying on of hands" on the well
      being of patients with advanced cancer is more efficient when performed by a
      person with self-declared "healing powers" as compared to an actor mimicking the
      healer in close detail. MATERIALS AND METHODS: A total of 80 patients were
      registered to participate in a randomized, single-blind phase III trial to
      evaluate the difference in efficacy of "laying on of hands" by either a "healer"
      or an actor. Each group consisted of 40 patients, scheduled to receive treatment
      for 5 min, three times a week. The effect of treatment was measured using a "Well
      Being scale", with the difference of the average score of the "Well-Being scale"
      on day 10 being defined as primary and that on day 5 as secondary endpoint. MAIN
      RESULTS: There was no significant difference in average score values between the
      "healer" and the actor with regard to the primary (p = 0.34) or the secondary
      endpoint (p = 0.94), but the comparison was limited due to major protocol
      violations by the "healer" who unblinded his status after the first run and quit
      the study. The study was completed by the actor as a descriptive, explorative
      study on the impact of "laying on of hands". A significant improvement in
      symptoms after treatment was found on day 5 (p < 0.001) and on day 10 (p =
      0.0002). CONCLUSION: "Laying on of hands" resulted in a significant improvement
      of cancer- or cancer-therapy-associated symptoms. The magnitude of improvement
      obtained was similar whether on a self-declared-healer- or an actor-provided
      "treatment".

PMID- 17039381
TI  - Levorphanol: the forgotten opioid.
AB  - BACKGROUND: Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a strong opioid
      that is the only available opioid agonist of the morphinan series. Levorphanol
      was originally synthesized as a pharmacological alternative to morphine more than
      40 years ago. It is considered a step-3 opioid by the World Health Organization
      (WHO) and has a greater potency than morphine. Analgesia produced by levorphanol
      is mediated via its interactions with mu, delta, and kappa opioid receptors.
      Levorphanol is also an N-methyl-D-aspartate (NMDA) receptor antagonist. There is
      evidence that levorphanol may inhibit uptake of norepinephrine and serotonin.
      Similar to morphine, levorphanol undergoes glucuronidation in the liver, and the
      glucuronidated products are excreted in the kidney. Levorphanol can be given
      orally, intravenously, and subcutaneously. OBJECTIVE: This article reviews the
      pharmacodynamics, pharmacology, and clinical efficacy for this often overlooked
      step-3 opioid. CONCLUSION: The long half-life of the drug increases the potential
      for drug accumulation. Levorphanol has clinical efficacy in neuropathic pain.

PMID- 17039382
TI  - Computer analysis of the safety of using three different pedicular screw
      insertion points in the lumbar spine in the Chinese population.
AB  - To help decide the best starting point for lumbar spine pedicle screw insertion
      in the Chinese population using three different techniques (Roy-Camille, Magerl,
      and Du). Three-dimensional CT reconstructions were created from 40 adult lumbar
      vertebral segments. Three different starting points for lumbar pedicle screw
      insertion were used. The direction of the pedicle screw through each hole was
      simulated on three-dimensional reconstructed images. Precise CT measurements were
      made to assess the distance from the simulated screw and the medial and lateral
      pedicle walls at the smallest transverse section of each pedicle. To measure a
      pedicle transverse section angle (TSA) lines were drawn on a CT scan in the
      direct axis of the pedicle, tangential to the medial, and separately lateral,
      walls of the pedicles at the isthmus. The angle these lines made with an anterior
      to posterior line, which directly bisected the mid-portion of the vertebral body
      was called the TSA. The greater the difference between the TSA between the medial
      and lateral walls provides the greatest flexibility for the insertion angle of
      the pedicle screw. Additionally, the distance from a line drawn in the direct
      central axis of the pedicle was measured from the point of exit from the pedicle
      to the entry point of each of three insertion techniques (Du, Mageral, and Roy
      Camille), to help understand potential risk factors. There were statistically
      significant differences between the distances from the entrance point to the
      direct pedicle axis among the three methods (P < 0.001). Du's insertion point was
      the shortest from L1 to L4. The distances measured following Magerl's technique
      were shortest at L5 (P < 0.05). There was no significant difference of the safe
      range of the TSA between the three methods from L1 and L2 (P > 0.05), but
      significant differences at L3, L4, and L5 (P < 0.05). At L3 and L4 the safe
      ranges of TSA using Du and Magerl's methods were significantly larger than those
      measured by Roy-Camille (P < 0.05). At L5 the safe ranges of TSA for the Magerl
      technique were the greatest among the three methods (P < 0.05). These results
      demonstrate that Du's method provides the safest starting point to place pedicle
      screws from L1 to L4, as its distance from the entrance point to the pedicle axis
      is the shortest and the safe range of TSA the largest of the three techniques.
      Magerl's technique can be safely used in the pedicles from L3 to L5, and is the
      safest choice at L5. Roy-Camille's technique is most applicable at L1 and L2, but
      has the highest risk when applied from L3 to L5.

PMID- 17039383
TI  - New chromogenic and fluorogenic reagents and sensors for neutral and ionic
      analytes based on covalent bond formation--a review of recent developments.
AB  - To date, hydrogen bonding and Coulomb, van der Waals and hydrophobic interactions
      are the major contributors to non-covalent analyte recognition using ionophores,
      ligands, aptamers and chemosensors. However, this article describes recent
      developments in the use of (reversible) covalent bond formation to detect analyte
      molecules, with special focus on optical signal transduction. Several new
      indicator dyes for analytes such as amines and diamines, amino acids, cyanide,
      formaldehyde, hydrogen peroxide, organophosphates, nitrogen oxide and nitrite,
      peptides and proteins, as well as saccharides have become available. New means of
      converting analyte recognition into optical signals have also been introduced,
      such as colour changes of chiral nematic layers. This article gives an overview
      of recent developments and discusses response mechanisms, selectivity and
      sensitivity.

PMID- 17039384
TI  - Achieving interlocking nails without using an image intensifier.
AB  - Interlocking nails are commonly performed using an image intensifier. These are
      expensive and are not readily available in most resource-poor countries of the
      world. The aim of this study was to achieve interlocking nailing without the use
      of an image intensifier. This is a prospective descriptive analysis of 40
      consecutive cases seen with shaft fractures of the humerus, femur, and tibia.
      Fracture fixation was done using Surgical Implant Generation Network (SIGN)
      nails. Forty limbs in 34 patients were studied. There were 12 females and 22
      males, giving a ratio of 1:2. The mean age (years) was 35.75+/-13.16 and the
      range was 17-70 years. The studied bones were: humerus 10%, femur 65%, and tibia
      25%. The fracture lines were: transverse 40%, oblique 15%, and communited 45%.
      Fracture grades were: closed 90%, grade I, 5%, grade II, 2.5%, and grade IIIA,
      2.5%. Surgical approaches were: antegrade 62.5% and retrograde 37.5%. Indications
      for fixation were: recent fracture 92.5%, non-union 5%, and malunion 3%. Methods
      of reductions were: open 85% and closed 15%. The mean follow-up period (years)
      was 1.50+/-0.78. The union time averaged 3 months. Complication was mainly screw
      loosening due to severe osteoporoses in one case. It is, therefore, concluded
      that, with the aid of external jigs and slot finders, interlocking can be
      achieved without an image intensifier.

PMID- 17039385
TI  - Paediatric thoracic tumours presenting as empyema.
AB  - Ultrasonography (US) is considered to be adequate for the preoperative evaluation
      of childhood empyema. This study was aimed to improve awareness that paediatric
      intra-thoracic tumours can mimic childhood post-pneumonic empyema and highlights
      the value of computed tomogram (CT) scan with intravenous (IV) contrast in
      preoperative evaluation of childhood empyema. The data were analysed on eight
      children (four boys and four girls) presented at the median age of 6.2 years (1.8
      15 years) for the management of empyema and later confirmed to have intra
      thoracic tumours. Intra-thoracic tumours in 8 (5.3%) children out of 150 cases of
      post-pneumonic empyema were managed during the study period. All eight had
      clinical features, increased white cell count, raised inflammatory markers and
      biochemical parameters suggestive of childhood empyema. Chest X-ray showed
      localised opacity in 3/8 while in other five suggested significant pleural
      collection with mediastinal shift. Additional investigations in referring
      hospital were suggestive of empyema in four children; US in three, CT scan
      without IV contrast in one. Referring hospital carried out non-diagnostic
      thoracocentesis in four children with blood stained pleural tap in two. In four
      children corroborative evidence suggestive of infection within pleural cavity and
      acute respiratory distress led to an emergency mini-thoracotomy resulting in
      significant intra-operative bleeding in two children. Histology on biopsy of the
      infected material showed primitive neuroectodermal tumour (PNET) in one,
      pleuropulmonary blastoma in one, metastatic malignant melanoma in one and
      cytology of pleural fluid diagnosed lymphoma in one. Pre-operative CT scan with
      IV contrast in four children correctly identified underlying intra-thoracic
      tumour (two benign teratoma, two PNET). In two cases CT with IV contrast was
      performed because chest X-ray suggested mediastinal loculated empyema while in
      other two high clinical index of suspicion prompted preoperative evaluation with
      CT scan with IV contrast. We advocate caution and increased awareness before
      considering therapeutic options in childhood empyema and recommend preoperative
      CT scan with IV contrast in some selected and unusual cases.

PMID- 17039386
TI  - Hemorrhoidopexy staple line height predicts return to work.
AB  - PURPOSE: Previous studies identified reduction in pain and complications with
      stapled hemorrhoidopexy relative to conventional hemorrhoidectomy. Previously,
      the presence of resected squamous epithelium and a staple line height <20 mm
      above the dentate line were predictive of postoperative pain. The purpose of this
      study was to further investigate and refine the role of staple height in the
      prediction of postoperative outcomes. METHODS: From July 2002 to October 2004, 75
      patients with symptomatic Grade 3 and 4 mixed hemorrhoids underwent stapled
      hemorrhoidopexy in two teaching institutions with prospective data collection.
      All procedures were performed under the direct supervision of two colorectal
      teaching staff. The majority were performed under monitored anesthesia care as
      outpatient procedures. Preoperative, intraoperative, and postoperative patient
      characteristics were evaluated. This included demographics, staple line height,
      specimen histology, complications, days to return to work, duration of narcotic
      pain medicine, and preoperative/postoperative tone and seepage. The results were
      subjected to statistical analysis using t-test and ANOVA. RESULTS: Seventy-five
      patients with a median age of 49 (range, 25-87) years were identified. Histology
      identified 62 specimens with columnar and/or transitional cells, 10 with squamous
      epithelium, and 3 with muscle present. Overall complication rate was 14 percent.
      Complications included three readmissions for pain control, three acute
      postoperative anal fissures, two postoperative bleeds (with one requiring
      examination under anesthesia without intervention), one patient with subcutaneous
      emphysema, and one admission for fecal impaction. Staple line height was not a
      statistically significant predictor of postoperative complication. Median return
      to work was 14 (range, 1-31) days. Median duration of narcotic use was six
      (range, 0-40) days. Patients with a staple line height>22 mm required a
      significantly shorter duration of narcotic pain management (P=0.024). Median
      follow-up was 24 (range, 9-253) days. Staple line heights below 20 mm had a mean
      return to work of 15 days. A staple line height>20 mm had a mean return to work
      of nine days. Staple line height was inversely related to return to work
      (P=0.01). CONCLUSIONS: A hemorrhoidopexy staple line>or=22 mm above the dentate
      line correlates with a significantly shorter need for postoperative narcotics
      (P=0.024) and an earlier return to work (P=0.017). Staple line distance above the
      dentate line meaningfully impacts comfort-based outcomes.

PMID- 17039387
TI  - Perforated rectal cancer associated with neoadjuvant radiotherapy: report of four
      cases.

PMID- 17039388
TI  - Innovative effect of illite on improved microbiological conversion of L-tyrosine
      to 3,4 dihydroxy phenyl L-alanine (L-DOPA) by Aspergillus oryzae ME2 under acidic
      reaction conditions.
AB  - In the present investigation, the previous ultraviolet irradiated mutant strain
      of Aspergillus oryzae UV-7 was further improved in terms of 3,4 dihydroxy phenyl
      L-alanine (L-DOPA) activity after chemical mutagenesis through 1-methyl 3-nitro 1
      nitroso guanidine (MNNG = 250-1500 microg/ml) treatment (0-30 min). Among several
      mutant variants, the one that produced a larger amount of L-DOPA from L-tyrosine
      was designated to as ME2 and it was made 2-deoxy-D-glucose-resistant by growing
      it at various concentrations of 2 dg (0.01-0.025 %, w/v) in Vogel's agar medium.
      Relatively better production of L-DOPA (> 0.60 mg/ml) was obtained when 2.0%
      (w/v) glucose was used as a carbon source in the mycelium production medium and
      the tyrosinase activity increased constitutively (1.08 mg/ml), which resulted in
      a greater production of L-DOPA. At optimum pH0 (pH 6.0) and reaction time (60
      min), more than 65% sugar was utilized for cell mass formation. The maximum
      conversion of L-tyrosine to L-DOPA (0.428 mg/ml) was achieved 60 min after the
      biochemical reaction. Mould mycelium was used for microbiological conversion of L
      tyrosine to L-DOPA because tyrosinases, beta-carboxylases, and tyrosine
      hydroxylases are intracellular enzymes. The effect of illite (1.0 x 10(6)-6.0 x
      10(6) M) on biochemical conversion of L-tyrosine to L-DOPA by Aspergillus oryzae
      ME(2 )was also carried out. Best results of L-DOPA biosynthesis were observed
      when the concentration of illite was 3.5 x 10(-6) M (1.686 mg/ml L-DOPA produced
      with 1.525 mg/ml consumption of L-tyrosine). It was noted that the addition of
      illite not only increased enzyme activity but also enhanced the permeability of
      cell membrane to facilitate the secretion of enzymes into the reaction broth. The
      comparison of kinetic parameters showed the ability of mutant to yield L-DOPA
      (i.e., Yp/x 7.360 +/- 0.04 mg/mg). When the culture grown on various illite
      concentrations was monitored for Qp, Qs, and qp, there was significant
      enhancement (p < 0.025) in these variables over the control, which indicate that
      the study can be commercially applicable on stirred and magnetic rotary drums.
      Overall, there was up to 3-fold (Qp = 0.290 mg/L-DOPA produced/ml/h) enhancement
      in the product formation rate, which is highly encouraging (HS, LSD 0.456).

PMID- 17039389
TI  - Directions of change in land cover and landscape patterns from 1957 to 2000 in
      agricultural landscapes in NW Spain.
AB  - The aim of this work is the analysis of the dynamics in cultural landscapes,
      focused on the spatial distribution of changes in land cover and landscape
      patterns, and their possible linkages. These dynamics have been analyzed for the
      years 1957 and 2000 in a sector of the north of Galicia (NW Spain) characterized
      with diverse landscapes. Afforestation processes linked to agriculture
      abandonment and forestry specialization were the main processes observed in the
      study area, with the exception of the southern mountainous sector that was
      dominated by ploughing of scrubland for conversion into grassland, reflecting a
      specialization in livestock production. The structural changes that have taken
      place in most of the study area were related to the heterogeneity aspects,
      although the mountainous sectors were characterized by changes in heterogeneity
      and fragmentation. According to the tests performed, the comparison of the
      spatial distribution of both dynamics showed a certain statistical significance,
      reflecting the interrelationship between patterns and processes. This approach
      could be useful for the identification of areas with similar characteristics in
      terms of spatial dynamics so as to define more effective and targeted landscape
      planning and management strategies.

PMID- 17039390
TI  - Policy windows, policy change, and organizational learning: watersheds in the
      evolution of watershed management.
AB  - Employing in-depth, elite interviews, this empirical research contributes to
      understanding the dynamics among policy windows, policy change, and
      organizational learning. First, although much of the research on agenda setting
      how issues attract enough attention that action is taken to address them-has been
      conducted at the national scale, this work explores the subnational, regional
      scale. With decentralization, regional-scale environmental decision-making has
      become increasingly important. Second, this research highlights the role of
      policy windows and instances of related organizational learning identified by
      natural resources managers. Having practitioners identify focusing events
      contrasts with the more typical approach of the researcher identifying a
      particular focusing event or events to investigate. A focusing event is a sudden,
      exceptional experience that, because of how it leads to harm or exposes the
      prospect for great devastation, is perceived as the impetus for policy change.

PMID- 17039391
TI  - A Water Quality Index applied to an international shared river basin: the case of
      the Douro River.
AB  - A Water Quality Index (WQI) is a numeric expression used to evaluate the quality
      of a given water body and to be easily understood by managers. In this study, a
      modified nine-parameter Scottish WQI was used to assess the monthly water quality
      of the Douro River during a 10-year period (1992-2001), scaled from zero (lowest)
      to 100% (highest). The 98,000 km(2) of the Douro River international watershed is
      the largest in the Iberian Peninsula, split between upstream Spain (80%) and
      downstream Portugal (20%). Three locations were surveyed: at the Portuguese
      Spanish border, 350 km from the river mouth; 180 km from the mouth, where the
      river becomes exclusively Portuguese; and 21 km from the mouth. The water
      received by Portugal from Spain showed the poorest quality (WQI 47.3 +/- 0.7%);
      quality increased steadily downstream, up to 61.7 +/- 0.7%. In general, the water
      quality at all three sites was medium to poor. Seasonally, water quality
      decreased from winter to summer, but no statistical relationship between quality
      and discharge rate could be established. Depending on the location, different
      parameters were responsible for the episodic decline of quality: high
      conductivity and low oxygen content in the uppermost reservoir, and fecal
      coliform contamination downstream. This study shows the need to enforce the
      existing international bilateral agreements and to implement the European Water
      Quality Directive in order to improve the water quantity and quality received by
      the downstream country of a shared watershed, especially because two million
      inhabitants use the water from the last river location as their only source of
      drinking water.

PMID- 17039392
TI  - Prognostic indicators for patients undergoing cytoreductive surgery and
      perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal
      mesothelioma.
AB  - BACKGROUND: This study evaluates clinical, radiological and histopathological
      prognostic indicators for survival of patients undergoing cytoreductive surgery
      and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal
      mesothelioma (DMPM). METHODS: Sixty-two consecutive patients with DMPM underwent
      cytoreduction and perioperative intraperitoneal chemotherapy at the Washington
      Cancer Institute. Twenty-six clinical, radiological and histopathological
      parameters were analyzed in univariate and multivariate analyses using overall
      survival as an endpoint. RESULTS: The overall survival was 79 months (range 1-143
      months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively.
      The following 14 prognostic variables were significant for survival in the
      univariate analysis: gender (P = .045), peritoneal cancer index (P = .038),
      completeness of cytoreduction score (P = .010), interpretive CT findings of the
      small bowel and mesentery (P = .001), mesothelioma cell type (P < .001),
      mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001),
      mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P <
      .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma
      pattern (P < .001) and depth of invasion (P = .014). In the multivariate
      analysis, the only factor that was independently associated with an improved
      survival after cytoreduction and perioperative intraperitoneal chemotherapy was
      mesothelioma nuclear size. CONCLUSIONS: Mesothelioma nuclear size was the
      dominant factor determining overall survival in patients with DMPM. A
      histopathological staging system based on measurement of the nuclear size was
      proposed.

PMID- 17039393
TI  - Which screening strategy using BMD measurements would be most cost effective for
      hip fracture prevention in elderly women? A decision analysis based on a Markov
      model.
AB  - INTRODUCTION: Hip fractures are responsible for excessive mortality, decreasing
      the 5-year survival rate by about 20%. From an economic perspective, they
      represent a major source of expense, with direct costs in hospitalization,
      rehabilitation, and institutionalization. The incidence rate sharply increases
      after the age of 70, but it can be reduced in women aged 70-80 years by
      therapeutic interventions. Recent analyses suggest that the most efficient
      strategy is to implement such interventions in women at the age of 70 years. As
      several guidelines recommend bone mineral density (BMD) screening of
      postmenopausal women with clinical risk factors, our objective was to assess the
      cost-effectiveness of two screening strategies applied to elderly women aged 70
      years and older. METHODS: A cost-effectiveness analysis was performed using
      decision-tree analysis and a Markov model. Two alternative strategies, one
      measuring BMD of all women, and one measuring BMD only of those having at least
      one risk factor, were compared with the reference strategy "no screening". Cost
      effectiveness ratios were measured as cost per year gained without hip fracture.
      Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY
      cohorts. RESULTS: In this model, which is mostly based on observed data, the
      strategy "screen all" was more cost effective than "screen women at risk." For
      one woman screened at the age of 70 and followed for 10 years, the incremental
      (additional) cost-effectiveness ratio of these two strategies compared with the
      reference was 4,235 euros and 8,290 euros, respectively. CONCLUSION: The results
      of this model, under the assumptions described in the paper, suggest that in
      women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry
      (DXA) would be more effective than no screening or screening only women with at
      least one risk factor. Cost-effectiveness studies based on decision-analysis
      trees maybe useful tools for helping decision makers, and further models based on
      different assumptions should be performed to improve the level of evidence on
      cost-effectiveness ratios of the usual screening strategies for osteoporosis.

PMID- 17039394
TI  - Preliminary evidence on existence of transplasma membrane electron transport in
      Entamoeba histolytica trophozoites: a key mechanism for maintaining optimal redox
      balance.
AB  - Entamoeba histolytica, an amitochondriate parasitic protist, was demonstrated to
      be capable of reducing the oxidized form of alpha-lipoic acid, a non permeable
      electron acceptor outside the plasma membrane. This transmembrane reduction of
      non permeable electron acceptors with redox potentials ranging from -290 mV to
      +360 mV takes place at neutral pH. The transmembrane reduction of non permeable
      electron acceptors was not inhibited by mitochondrial electron transport
      inhibitors such as antimycin A, rotenone, cyanide and azide. However, a clear
      inhibition with complex III inhibitor, 2-(n-heptyl)-4-hydroxyquinoline-N-oxide;
      modifiers of sulphydryl groups and inhibitors of glycolysis was revealed. The
      iron-sulphur centre inhibitor thenoyltrifluoroacetone failed to inhibit the
      reduction of non permeable electron acceptors whereas capsaicin, an inhibitor of
      energy coupling NADH oxidase, showed substantial inhibition. p
      trifluromethoxychlorophenylhydrazone, a protonophore uncoupler, resulted in the
      stimulation of alpha-lipoic acid reduction but inhibition in oxygen uptake.
      Mitochondrial electron transport inhibitors substantially inhibited the oxygen
      uptake in E. histolytica. Transmembrane reduction of alpha-lipoic acid was
      strongly stimulated by anaerobiosis and anaerobic stimulation was inhibited by 2
      (n-heptyl)-4-hydroxyquinoline-N-oxide. Transmembrane redox system of E.
      histolytica was also found to be sensitive to UV irradiation. All these findings
      clearly demonstrate the existence of transplasma membrane electron transport
      system in E. histolytica and possible involvment of a naphthoquinone coenzyme in
      transmembrane redox of E. histolytica which is different from that of mammalian
      host and therefore can provide a novel target for future rational
      chemotherapeutic drug designing.

PMID- 17039395
TI  - Potential roles of 3'-5' exonuclease activity of NM23-H1 in DNA repair and
      malignant progression.
AB  - NM23-H1 is a metastasis suppressor protein that exhibits 3'-5' exonuclease
      activity in vitro. As 3'-5' exonucleases are generally required for maintenance
      of genome integrity, this activity represents a plausible candidate mediator of
      the metastasis suppressor properties of the NM23-H1 molecule. Consistent with an
      antimutator function, ablation of the yeast NM23 homolog, YNK1, results in
      increased mutation rates following exposure to UV irradiation and exposure to the
      DNA damaging agents etoposide, cisplatin, and MMS. In human cells, a DNA repair
      function is further suggested by increased NM23-H1 expression and nuclear
      translocation following DNA damage. Also, forced expression of NM23-H1 in NM23
      deficient and metastatic cell lines results in coordinate downregulation of
      multiple DNA repair genes, possibly reflecting genomic instability associated
      with the NM23-deficient state. To assess the relevance of the 3'-5' exonuclease
      activity of NM23-H1 to its antimutator and metastasis suppressor functions, a
      panel of mutants harboring defects in the 3'-5' exonuclease and other enzymatic
      activities of the molecule (NDPK, histidine kinase) have been expressed by stable
      transfection in the melanoma cell line, 1205Lu. Pilot in vivo metastasis assays
      indicate 1205Lu cells are highly responsive to the metastasis suppressor effects
      of NM23-H1, thus providing a valuable model for measuring the extent to which the
      nuclease function opposes metastasis and metastatic progression.

PMID- 17039396
TI  - Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway
      epithelia.
AB  - This review integrates recent understanding of a novel role for NDPK-A in two
      related directions: Firstly, its role in an airway epithelial cell when bound to
      the luminal (apical) membrane and secondly in the cytosol of many different cells
      (epithelial and non-epithelial) where an isoform-specific interaction occurs with
      a regulatory partner, AMPKalpha1. Thus NDPK-A is present in both a membrane and
      cytosolic environment but in the apical membrane, its roles are not understood in
      detail; preliminary data suggest that it co-localises with the cystic fibrosis
      protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic
      alpha1 isoform of the AMP-activated protein kinase (AMPKalpha subunit), which is
      part of a heterotrimeric protein complex that responds to cellular energy status
      by switching off ATP-consuming pathways and switching on ATP-generating pathways
      when ATP is limiting. We find that ATP is located within this complex and 'fed'
      from NDPK to AMPK without ever 'seeing' bulk solution. Importantly, the reverse
      can also happen such that AMPK activity can be made to decline when NDPK-A
      'steals' ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by
      suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP.

PMID- 17039397
TI  - Promoting positive adolescent development for at-risk students with a student
      assistance program.
AB  - This study evaluated the psycho-educational small-group component of the CASPAR
      Youth Services Student Assistance Program with a randomized-controlled trial. Two
      cohorts of at-risk sixth graders from six schools in two communities were
      randomly assigned to intervention or control conditions and tested one and a half
      years later at the end of the seventh grade. A generalized estimating equations
      model yielded a significant intervention effect on all three composite outcome
      variables. The results support the effectiveness of prevention strategies aimed
      at promoting positive youth development and a social influence process for
      adolescents that creates trusting relationships as the foundation for helping
      youth improve key skills, exert greater control over their lives, and make
      informed decisions about substances. EDITOR'S STRATEGIC IMPLICATIONS: School
      administrators should be aware of this promising approach (pending replication)
      of using student assistance counselors to promote children's intrinsic motivation
      and potential for positive decision making.

PMID- 17039398
TI  - Implementing an evidence-based preventive intervention in neighborhood family
      centers: examination of perceived barriers to program participation.
AB  - : This study examined parents' perceived barriers to participation in a
      multicomponent prevention program implemented by a community agency serving
      culturally diverse urban neighborhoods. The Early Risers Participation Interview
      (ER-PI), modeled after Kadzin et al.'s (1997) Barriers to Treatment Participation
      Scale, was administered to parents (N = 138) of children who were screened for
      disruptive behavior and were randomized into a two-year intervention condition.
      Results showed that the perceived barriers score provided significant information
      in differentiating low and high participators after controlling for child,
      parent, and family characteristics. Early identification and resolution of
      parents' perceived barriers to participation may be key to implementing
      multifaceted preventive programs successfully in inner-city neighborhoods.
      EDITOR'S STRATEGIC IMPLICATIONS: The authors present promising practices for
      client engagement and retention. The experimental, longitudinal design is
      notable, especially in the evaluation of a community-run prevention program.

PMID- 17039399
TI  - Images in neuro-oncology: rapid development of osseous and chondrous metaplasia
      in recurrent anaplastic ependymoma.

PMID- 17039400
TI  - Oligodendroglioma with neurocytic differentiation versus atypical
      extraventricular neurocytoma: a case report of unusual pathologic findings of a
      spinal cord tumor.
AB  - Differentiating oligodendroglioma from extraventricular neurocytoma by
      conventional light microscopy alone can present a diagnostic challenge. We report
      pathologic findings of an unusual spinal cord tumor from a 33-year-old male
      patient which showed hybrid features of oligodendroglioma and extraventricular
      neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary
      mass in the cervicothoracic region (C7 through T6). Histologic examination
      revealed a clear cell neoplasm containing ganglion-like cells and calcifications,
      prompting the differential diagnosis of oligodendroglioma and extraventricular
      neurocytoma. The immunohistochemical analysis disclosed neural differentiation of
      the neoplastic cells with strong synaptophysin and neurofilament staining
      consistent with extraventricular neurocytoma, as well as strong S-100 and glial
      fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent
      in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a
      finding commonly observed in oligodendroglioma. The proliferation index (using
      antibody MIB1) of the tumor was approximately 30%. The morphologic findings and
      these results strengthen the hypothesis that these tumors may share a common
      progenitor cell, which has also been observed by others. Because there are
      differences in patient management and long-term prognosis, it is important to
      attempt to distinguish between oligodendroglioma and neurocytoma. This unusual
      case and similar rare reported cases support the need to reclassify tumors
      showing pathologic features common to both neurocytoma and oligodendroglioma as a
      unique entity, while the effort continues to identify the cell of origin.

PMID- 17039401
TI  - Increased level of tetrahydro-beta-carboline derivatives in short-term fermented
      garlic.
AB  - In our previous study [1], we found that relatively short-term spontaneous
      fermentation (40 days at 60-70 degrees C, 85-95% relative humidity) potentiates
      anti-oxidative properties of garlic, in which scavenging activity against
      hydrogen peroxide was included. Since tetrahydro-beta-carboline derivatives
      (THbetaCs) that possess hydrogen peroxide scavenging activity have recently been
      identified in aged garlic extract, THbetaCs were quantitatively analyzed with
      liquid chromatography-mass spectrometry (LC-MS). (1R, 3S)-1-Methyl-1,2,3,4
      tetrahydro-beta-carboline-3-carboxylic acid (MTCC) and (1S, 3S)-MTCC were found
      in the fermented garlic extract whereas only trace levels of MTCCs were detected
      in the row garlic extract. Therefore, it is suggested that relatively short-term
      fermentation potentiates scavenging activity of garlic against hydrogen peroxide
      by forming THbetaCs, especially MTCCs.

PMID- 17039402
TI  - Gender differences in pornography consumption among young heterosexual Danish
      adults.
AB  - The aims of the study were (1) to investigate gender differences in pornography
      consumption among Danish adults aged 18-30 and (2) to examine gender differences
      in situational, interpersonal, and behavioral characteristics of pornography
      consumption. A national survey study was conducted using a representative sample
      of 688 young heterosexual Danish adult men and women. The study found large
      gender differences in prevalence rates of pornography consumption and consumption
      patterns. Compared to women, men were exposed to pornography at a younger age,
      consumed more pornography as measured by time and frequency, and used pornography
      more often during sexual activity on their own. Gender differences in the
      interpersonal context of use were also evident, with women using pornography more
      often with a regular sexual partner than men. In turn, men were found to use
      pornography more often on their own or with friends (non-sexual partners) than
      women. For both men and women, the usual place of use was home and no significant
      gender difference was found in this regard. Men and women were found to vary in
      their preferences in pornographic materials, with men both preferring a wider
      range of hardcore pornography and less softcore pornography than women. Gender
      differences in sexual behavioral factors were limited to masturbation patterns
      with men masturbating more than women. Male gender, higher frequency of
      masturbation, lower age at first exposure, and younger age were found to account
      for 48.8% of the total variance of pornography consumption. The results were
      discussed in relation to the sociocultural environment and evolutionary theory.
      It is argued that gender differences in social acceptability, adherence to gender
      stereotypes, traditions of gender sexuality, gender norms, and mating strategies
      are key factors in understanding gender differences in pornography consumption.

PMID- 17039403
TI  - Childhood family correlates of heterosexual and homosexual marriages: a national
      cohort study of two million Danes.
AB  - Children who experience parental divorce are less likely to marry heterosexually
      than those growing up in intact families; however, little is known about other
      childhood factors affecting marital choices. We studied childhood correlates of
      first marriages (heterosexual since 1970, homosexual since 1989) in a national
      cohort of 2 million 18-49 year-old Danes. In multivariate analyses, persons born
      in the capital area were significantly less likely to marry heterosexually, but
      more likely to marry homosexually, than their rural-born peers. Heterosexual
      marriage was significantly linked to having young parents, small age differences
      between parents, stable parental relationships, large sibships, and late birth
      order. For men, homosexual marriage was associated with having older mothers,
      divorced parents, absent fathers, and being the youngest child. For women,
      maternal death during adolescence and being the only or youngest child or the
      only girl in the family increased the likelihood of homosexual marriage. Our
      study provides population-based, prospective evidence that childhood family
      experiences are important determinants of heterosexual and homosexual marriage
      decisions in adulthood.

PMID- 17039405
TI  - Family correlates of comorbid anxiety disorders in children with attention
      deficit/hyperactivity disorder.
AB  - This study evaluated parental anxiety and parenting practices associated with
      comorbid Anxiety Disorders among children with Attention Deficit/Hyperactivity
      Disorder. Clinic-referred families (n=143) were diagnosed using DSM criteria.
      Parents and children completed measures of parenting practices. Comorbid anxiety
      in children was significantly associated with maternal anxiety,
      overprotectiveness, and a lack of positive parenting. The relative odds of
      comorbid anxiety appeared to be especially high when all three factors were
      present. These findings are consistent with theory linking those three family
      factors to the development of anxiety in all children. Implications for
      adjunctive treatment of anxiety that is comorbid with ADHD are discussed.

PMID- 17039404
TI  - Phase II study of amrubicin in previously untreated patients with extensive
      disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study.
AB  - PURPOSE: To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl
      9-amino-7-[(2-deoxy-beta-D-erythro-pentopyranosyl )oxy]-7,8,9,10-tetrahydro-6,11
      dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients
      with extensive-disease small cell lung cancer (SCLC). PATIENTS AND METHODS: A
      total of 35 previously untreated patients with extensive-disease SCLC were
      entered into the study. Amrubicin was given by daily intravenous infusion at 45
      mg/m(2)/day for 3 consecutive days, every 3 weeks. Unless there was tumor
      regression of 25% or greater after the first cycle, or 50% or greater after the
      second cycle, treatment was switched to salvage chemotherapy in combination with
      etoposide (100 mg/m(2), days 1, 2, and 3) and cisplatin (80 mg/m(2), day 1).
      RESULTS: Of the 35 patients entered, 33 were eligible and assessable for efficacy
      and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95%
      confidence interval [CI], 1.9-24.3%) and 22 had a partial response, for an
      overall response rate of 75.8% (95% CI, 57.7-88.9%). Median survival time was
      11.7 months (95% CI, 9.9-15.3 months), and 1-year and 2-year survival rates were
      48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non
      hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia
      (9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered
      to only 6 patients. CONCLUSION: Amrubicin was active for extensive-disease SCLC
      with acceptable toxicity. Further studies in combination with other agents for
      SCLC are warranted.

PMID- 17039406
TI  - Varicella-Zoster virus gene expression at variable periods following death in a
      rat model of ganglionic infection.
AB  - We used a rat model of Varicella-Zoster virus (VZV) ganglionic infection, which
      mirrors some of the features of VZV latency in humans, to determine the temporal
      pattern of expression of a VZV immediate-early gene (63) and a VZV late gene (40)
      at 0, 24 and 48 h after death of the animal. The immediate-early VZV gene 63 is
      known to be abundantly expressed during human ganglionic latency, while the late
      VZV gene 40 is not expressed during human latency. Using both RNA in situ
      hybridisation (ISH) and nested RT-PCR, it was found that at all time points in
      both thoracic and lumbar ganglia, the number of ganglia positive for VZV gene 63
      was higher than for gene 40. The expression of gene 40 did not increase with time
      postmortem (pm) These results provide indirect support for the hypothesis that
      patterns of expression of VZV genes detected in human tissue at even 48 h pm
      reflect the pattern of expression during human ganglionic latency.

PMID- 17039407
TI  - Evidence that PTB does not stimulate HCV IRES-driven translation.
AB  - It is now well established that Hepatitis C Virus (HCV) translation is driven by
      an Internal Ribosome Entry Site (IRES) resulting in cap-independent translation.
      Such a mechanism usually occurs with the help of IRES Associated Factors (ITAFs).
      Moreover, an important translational feature is likely conserved from the model
      of classical mRNA circularisation (5'-3' cross-talk), involving the HCV RNA
      highly structured 3' extremity called the 3'X region. This could bind several
      cellular factors and modulate the translation efficacy, at least in Rabbit
      Reticulocyte Lysate (RRL). In particular, polypyrimidine-binding proteins have
      been proposed to be potential HCV ITAFs, such as Polypyrimidine Tract Binding
      protein (PTB). However, contradictions still exist as to the role of PTB: its
      ability to bind both the HCV IRES and the 3'X region leads to the hypothesis that
      it could positively modulate IRES-driven translation in the presence of the X
      structure. Results of translational and PTB-binding studies of X mutant sequences
      led us to discredit PTB as protagonist of 3'X region stimulation on HCV IRES
      driven translation. Moreover, competition assays of X RNA in trans on IRES-driven
      translation demonstrate the involvement of at least two stimulating factors and
      led to the conclusion that this mechanism is more complex than initially thought.
      Although we did not identify these factors, it is no longer doubtful that there
      is effectively a stimulating functional interaction between the HCV IRES and the
      3'X region in RRL.

PMID- 17039408
TI  - A comparison of complete untranslated regions of measles virus genomes derived
      from wild-type viruses and SSPE brain tissues.
AB  - We compared complete untranslated regions (UTRs) of two subacute sclerosing
      panencephalitis (SSPE) measles virus (MV) strains and two wild-type (wt) MV
      strains, all belonging to the same genotype (D6). In comparison to wt MVs of the
      same genotype, base changes were identified in the two SSPE measles virus strains
      at 27 and 33 noncoding positions, respectively. Majority of these residues are
      unique for each of the SSPE virus sequences in comparison to all other reported
      measles virus strain sequences. The location of some of these changes indicates
      that they may modify cis-acting regulatory sequences including gene-end signal of
      the P gene, H/L gene junction and Kozak consensus element of the L gene. Further,
      within the long UTR between M and F genes, deletions and insertions were
      identified. Thus, our study could be significant for additional investigation
      using reverse genetics and recombinant viruses, of possible influence of
      mutations in UTRs on establishment and maintenance of chronic progressive CNS
      disease caused by MV persistence.

PMID- 17039409
TI  - Maintenance of the rat transgenic model of familial amyotrophic lateral sclerosis
      expressing human SOD1G93A mutation.
AB  - A colony of transgenic rats expressing the human mutant Cu,Zn superoxide
      dismutase gene (hSOD1G93A) that is associated with some cases of familial form of
      amyotrophic lateral sclerosis (ALS) has been maintained in the Animal House of
      the Polish Academy of Sciences Medical Research Centre since 2003. This
      transgenic model, generated by Howland et al. (Proc Natl Acad Sci USA 2002; 99:
      1604-1609), has been obtained under the material transfer agreement from Wyeth
      Corporation. The transgenic SOD1G93A (or 'Howland') rats develop neurological and
      neuropathological symptoms reminiscent of human ALS, i.e. progressive loss of
      motoneurons leading to paralysis and death. This paper describes maintenance of
      the transgenic rat colony, and general procedures used in experiments with these
      animals (i.e. genotyping, neurological observations, anaesthesia, etc.). At the
      beginning of the colony, up to the 3rd generation of the rats, symptoms of the
      model disease appeared at 95-125 days of age, and the animals survived till 120
      145 days of age. Thereafter a gradual change in the disease phenotype occurred,
      and in the 8th generation approximately 1/3 of the rats displayed much slowed
      disease progression.

PMID- 17039410
TI  - Morphological changes and selective loss of motoneurons in the lumbar part of the
      spinal cord in a rat model of familial amyotrophic lateral sclerosis (fALS).
AB  - Morphological alterations and the course of changes in motoneuron counts were
      studied by light microscopy (cresyl violet staining) in the L2/L3 region of the
      spinal cord of hemizygotic transgenic rats carrying the amyotrophic lateral
      sclerosis-associated mutant human gene for Cu,Zn superoxide dismutase (hSOD1G93A)
      and of their non-transgenic littermates. In 60-day old transgenic rats, a few
      ischaemic-looking alpha-motoneurons and occasional vacuolization and accumulation
      of tigroid in some of the cells were apparent. On day 93 of life more distinct
      cellular pathology was found in transgenic rats, including moderate gliosis,
      neuronophagy of alpha-motoneurons, and occasional neuronophagy of gamma
      motoneurons. In 120-day-old transgenic rats, abundant gliosis and profound
      neuronophagy of alpha-motoneurons were observed combined with occasional
      neuronophagy of other cells. Some loss of alpha-motoneurons was also apparent in
      120-day-old non-transgenic littermates of the transgenic rats. No difference in
      alpha-motoneuron and gamma-motoneuron counts was found between the rats on day 60
      of life (early presymptomatic stage of the model disease in the transgenic rats).
      At 93 days of age (late presymptomatic stage), alpha-motoneuron count, but not
      gamma-motoneuron count, tended to be lower (p=0.06) in the transgenic rats. On
      day 120 of life (symptomatic stage), alpha-motoneuron count in the transgenic
      rats was about half that in their nontransgenic littermates (p<0.001); at this
      time point the relative decline in alpha-motoneuron number in the former was 57%
      (day 120 versus day 60; p<0.001). A smaller decline in alpha-motoneuron count was
      also found in nontransgenic rats (day 120 vs day 60: 24%, p<0.05); this was not
      associated with the emergence of neurological symptoms or distinct changes in the
      cell morphology of the spinal cord region studied.

PMID- 17039411
TI  - Progression of morphological changes within CNS in a transgenic rat model of
      familial amyotrophic lateral sclerosis.
AB  - An analysis of the dynamics of histological and immunocytochemical changes in the
      CNS of a transgenic rat model of fALS in various periods of life was performed.
      Material was obtained from animals on the 60th day of age (4), 93rd day of age
      (3) and 120th presymptomatic day and from 3 animals in paretic stage of the
      disease. Formalin-fixed and paraffin-embedded slices were stained with HE and
      Kluver-Barrera method. Immunoreactions to GFAP, S-100, ferritin, neurofilament,
      ubiquitin, synaptophysin and tau protein were also performed. Within the brain
      tissues patchy neuronal loss and dark or ischaemic neurons were dispersed in
      cortical layers, CA1, CA3 and CA4 hippocampal areas and structures of the
      hemispheres and brain stem. In the spinal cord, numerous alpha motoneurons were
      dark or ischaemic. Vacuoles or small pale spots were visible in their cytoplasm.
      Microspongiosis surrounded some motoneurons, particularly cells subjected to
      neuronophagy. Neuronophagy, sporadically observed at the age of 60th day, was
      more extensive on the 93rd day of age, and at the age of 120 days already
      involved all interneurons of the anterior and posterior horns. In the immune
      reaction to neurofilament numerous fibres, often thick, fragmented or rosary
      like, were observed. They were located within subcortical white matter, external
      and internal capsules, anterior horns of the spinal cord. Changes became more
      intensive with age. Astrocytic reactivity was weak in animals on the 60th and
      93rd day of life. Non-numerous cells were immunoreactive to GFAP and S-100,
      although an increase of astrocytic nuclei was observed. On the 120th day of age
      and in symptomatic stage astrocytic hypertrophy and proliferation were intensive.
      But from the 60th day of age ubiquitin and tau protein immunopositive material
      was accumulated in the perinuclear area of astroglial cytoplasm. Immunoreaction
      of nerve cells to these proteins was negative. CONCLUSIONS: 1) In the subclinical
      stage of the disease the pathological process within the CNS takes place already
      on the 60th day of age and its intensity increases with age. 2) Morphological
      changes are not limited to motor neuronal cells. Various structures of the CNS
      are damaged. 3) Weak astroglial reaction probably depends on pathological
      accumulation of ubiquitin and tau protein in cytoplasm. 4) Astroglial cells are
      probably also a "target" for pathogenic factors in the rat model of fALS.

PMID- 17039412
TI  - Ultrastructural changes in lumbar spinal cord in transgenic SOD1G93A rats.
AB  - The purpose of this study was to determine structural changes which trigger the
      onset and progression of amyotrophic lateral sclerosis in rats expressing a human
      SOD1 transgene with mutation G93A. Lumbar spinal cord of affected rats in early
      and late presymptomatic (PM, 60 and 93 days of age) and symptomatic (S, 120 days
      of age) stage of the disease were analyzed ultrastructurally. At 60 days the
      structure of lumbar spinal cord as well as alpha motoneurons type S and F
      appeared normal; however, careful examination revealed that approximately 15% of
      axons were filled with mitochondria that were abnormal in number, size and
      morphology. Grossly swollen mitochondria with disrupted cristae were a prominent
      feature in all large axons at 93 days of age. At this time swelling and dilated
      mitochondria were observed also in type S motoneurons, while type F had small,
      well preserved mitochondria. At symptomatic stage the alpha motoneurons showed
      moderate neuronal loss, mainly of the S type. The most interesting finding at
      this stage was the occurrence of motoneurons with morphological signs of
      apoptotic-like degeneration. Such apoptotic-like motoneurons were characterized
      by nuclear and cytoplasmic condensation, chromatin compaction and formation of
      uniformly dense, dark structures. Numerous axons with very dark, compact interior
      as well as apoptotic bodies were irregularly scattered throughout the neuropil.
      Our ultrastructural study indicates that dying motoneurons in transgenic mutant
      SOD1G93A rats exhibit reminiscent apoptotic morphology which is preceded by
      significant mitochondrial abnormalities mainly in proximal axons and S
      motoneurons. Different reaction of slow and fast motoneurons to degenerating
      factors requires further analysis.

PMID- 17039413
TI  - Astroglial alterations in amyotrophic lateral sclerosis (ALS) model of slow
      glutamate excitotoxicity in vitro.
AB  - Chronic excitotoxicity mediated through defective glial and/or neuronal glutamate
      transport may contribute to several neurodegenerative diseases including
      amyotrophic lateral sclerosis (ALS). This study was performed to determine the
      ultrastructural characteristics of astroglial changes concomitant with motor
      neuron (MN) degeneration in a model of slow excitotoxicity in vitro. The study
      was performed on organotypic cultures of rat lumbar spinal cord subjected to the
      glutamate uptake blockers threohydroxyaspartate (THA) and L-trans-pyrrolidine-2,4
      dicarboxylate (PDC). The chronic inhibition of glutamate transport by THA and PDC
      resulted in slow degeneration of the rat's MNs accompanied by distinct glial
      changes predominantly involving protoplasmic astrocytes. The presence of
      irregular vacuoles and vesicles in the astroglial cells was frequently observed.
      Occasionally the astrocytes exhibited proliferation and accumulation of abnormal
      profiles of smooth endoplasmic reticulum. In 3 weeks there were no signs of
      increased production of glial filaments in the protoplasmic astrocytes. The
      results evidenced the coexistence of neuronal degeneration and astroglial
      abnormalities in an ALS model in vitro and suggested an active role of astrocytes
      contributing to the induction and propagation of MN degeneration.

PMID- 17039414
TI  - Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of
      patients with amyotrophic lateral sclerosis (ALS).
AB  - Aetiology and pathogenesis of amyotrophic lateral sclerosis (ALS) is still a
      mystery. Among several hypotheses autoimmune mechanisms are also taken into
      account. We report here our investigations of auto-antibodies against proteins of
      spinal cord cells in the cerebrospinal fluid (CSF) and serum of ALS patients. The
      results were correlated with the severity of disease course. The subjects were 57
      ALS patients (29 severe, 28 mild) and 10 normal controls. The major finding in
      CSF was the presence of antibodies against a 70 kD protein in the majority of ALS
      patients. This protein was identified as neurofilament 68. The second protein of
      high reactivity and frequency of appearance was a 82 kD protein, which was
      identified as a-actinin. Less reactive and less frequent were antibodies directed
      against 55 kD and 40 kD proteins. They were immunologically defined to be related
      to desmin and actin, resp. The difference between the reactivity of anti
      neurofilament and anti-desmin related protein in the severe and mild ALS groups
      was significant. More frequent were the anti-neurofilament antibodies in the
      severe ALS cases as compared to the milder ones. In normal CSF, antibodies
      directed against 55 kD, 70 kD and 82 kD proteins were present in traces and
      appeared in 5%, 20% and 10% of cases, respectively. In the serum of 30% of severe
      ALS patients traces of antibodies against 70 kD protein were detected. The
      morphological studies in the presence of CSF of ALS patients revealed pronounced
      immunoreactivity of spinal cord neurons, mainly within anterior horns. The
      significance of the presence of auto-antibodies in CSF of ALS patients against
      cellular proteins of the spinal cord is hard to define. It is conceivable that
      they appear as a secondary immunological consequence of neuronal death. It is
      also possible that they may accelerate the course of neuronal degeneration.

PMID- 17039415
TI  - Does the ganglion of Ribes exist?
AB  - Some have included the ganglion of Ribes (Francois Ribes, 1765-1845), lying on
      the anterior communicating artery, as the most superior ganglion of the
      sympathetic nervous system. To verify the presence of this structure, the
      anterior communicating artery was harvested from 40 fresh adult cadavers and
      histological analysis and immunochemistry performed. Grossly and with
      magnification, no ganglion-like structures were found in or around the anterior
      communicating artery in any specimen. However, scattered neuronal cell bodies
      were found in the adventitia of the anterior communicating artery with
      histological immunochemical analysis. Based on the lack of vasoactive intestinal
      peptide staining and the positive reaction to tyrosine hydroxylase, these neurons
      are most likely sympathetic in nature. Based on our findings, a grossly visible
      ganglion of Ribes does not exist. However, neuronal cell bodies were found in the
      adventitia of the anterior communicating artery although the function of such
      cells remains speculative.

PMID- 17039416
TI  - The brain immune response in human prion diseases. Microglial activation and
      microglial disease. I. Sporadic Creutzfeldt-Jakob disease.
AB  - A study of microglial activation and its contribution to the CNS immune response
      was performed on the brain autopsy material of 40 patients with definite sporadic
      Creutzfeldt-Jakob disease (sCJD). Spatial patterns of microglial activation and
      prion protein disease-associated (PrPd) deposition were compared in cerebellar
      and cerebral cortices using immunohistochemical (IHC) activation markers.
      Morphological phenotype forms of microglial cells in activation stages were
      assessed immunohistochemically (IHC). The immune inflammatory response dominated
      by microglia was found to be a characteristic feature in CJD. Differences in the
      intensity and patterns of microglial activation corresponded to variable patterns
      of PrP deposition, whereas the morphological phenotype forms of microglia were
      specific for activation stages. The presence of activated microglial cells in the
      various activation stages regardless of illness duration indicates continuous
      microglial activity and microglial contribution to the spread of infection for
      the whole symptomatic period of the disease. Remarkable vacuolar degeneration
      changes of numerous microglial cells in different activation stages including
      homing stage may suggest dysfunction of microglial immune surveillance in human
      sCJD that can significantly contribute to transmissible spongiform encephalopathy
      (TSE) pathogenesis.

PMID- 17039417
TI  - Activation of Akt and Erk pathways in medulloblastoma.
AB  - Medulloblastoma (MB) is the most common malignant brain tumour in children. Its
      aetiology is unknown, although several signalling pathways controlling cell
      proliferation are thought to participate in the progress of the neoplasm.
      Mutations of the genes encoding proteins participating in the pathways triggered
      by embryonic growth factors like Sonic hedgehog (Shh) or WNT are often found in
      MB. Another model of MB development is overexpression or mutation of several
      types of growth factor receptors, including IGF-IR, EGF-R and PDGFR, that have
      the ability to activate cellular kinases responsible for promoting cell
      proliferation. In order to test this hypothesis, in the current paper we tested
      the activation of two kinases, Akt/PKB (protein kinase B) and Erk (extracellular
      signal-regulated kinase) and their substrates in 10 sporadic medulloblastoma
      cases. We show that MBs are a highly heterogeneous group of tumours that show
      upregulation of various signalling pathways. Nevertheless, both Akt and Erk may
      contribute to the progression of MB, triggering, at least in some cases, the mTOR
      (mammalian target of rapamycin) pathway, controlling translation of several cell
      cycle-related proteins. We hypothesize that Akt and Erk activation may also be
      associated with downregulation of protein phosphatase 2A (PP2A).

PMID- 17039418
TI  - The role of trkB receptor in the formation of post-traumatic neuroma.
AB  - The outcome of peripheral nerve injury is often impaired by post-traumatic
      neuroma developing at the injury site. Neuroma is usually accompanied by
      neuropathic pain, which is usually resistant to most analgesics and presents a
      serious clinical problem. The mechanisms underlying post-traumatic neuroma remain
      unclear, but they are likely associated with regeneration processes. Brain
      derived neurotrophic factor (BDNF) and its receptor, trkB, are strongly
      implicated in axonal regeneration after injury. The aim of this work was to
      examine the role of trkB in post-traumatic neuroma formation. The sciatic nerve
      was transected in wild-type and heterozygous trkB-deficient mice. The nerve was
      either left cut or immediately sewn up or the gap injury model was performed. The
      gap was provided with an autologous or cross (obtained from another genetic
      group) graft. Sixteen weeks after surgery, the animals were sacrificed and
      histologic evaluations were performed. We found very limited or no neuroma
      formation in wild-type animals, regardless of the surgical procedure. In the
      majority of trkB-deficient mice, the post-traumatic neuroma was found at the end
      of the proximal stump of the transected nerve. In the gap injury model, in trkB
      deficient animals receiving wild-type graft, there was no neuroma at the join
      site between the graft and distal stump of the nerve. In contrast, if the graft
      was autologous, neuroma formed at both joints. We also noticed many more mast
      cells accumulated at the surgery site in trkB-deficient than in wild-type
      animals. These results indicate the important role of BDNF receptor in post
      traumatic neuroma formation.

PMID- 17039419
TI  - The role of the extracellular calcium-sensing receptor in health and disease.
AB  - The calcium-sensing receptor has a key role in calcium homeostasis, it is
      involved in the regulation of the serum calcium level within minutes via the
      secretion and action of parathyroid and the excretion of calcium in the kidney in
      a negative feedback manner. Mutations of the calcium sensing receptor gene leads
      to inactivating and activating mutations resulting in diseases with
      hypercalcaemia and hypocalcaemia. The loss of function mutations are associated
      with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant
      disease characterised by lifelong mild hypercalcaemia, low urinary calcium
      excretion, and inappropriate high parathyroid hormone levels, sometimes difficult
      to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with
      FHH did not profit from parathyroidectomy, a calcium lowering therapy is not
      necessary. The gain of function mutations of the calcium-sensing receptor are
      associated with autosomal dominant hypocalcaemia (ADH), a disease characterised
      by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium
      excretion and normal PTH levels. A therapy to raise the serum calcium
      concentration has to be done carefully and is only indicated in symptomatic
      patients, because of enhancement of hypercalciuria with the risk of
      nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium
      sensing receptor gene facilitates the sometimes difficult diagnosis. The
      development of compounds modulating the calcium sensing receptor function and
      thereby the section of PTH may become an important role in treatment of diseases
      of calcium metabolism.

PMID- 17039420
TI  - Impact of smoking on the course of Graves' disease after withdrawal of
      antithyroid drugs.
AB  - Cigarette smoking has been reported to alter relapse rate in patients with
      Graves' disease (GD). However, the predictive effect of smoking in GD patients
      after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A
      prospective multicenter trial has previously identified smoking as an independent
      risk factor for relapse. Based on this study, the present paper gives a more
      detailed analysis of the impact of smoking on the long-term course of GD after
      ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during
      two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later
      (visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than
      non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs.
      6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis
      showed a significantly higher relapse rate in smokers than non-smokers. A subset
      of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse
      during follow-up. Among them, smokers more often relapsed than non-smokers
      irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10
      IU/L the predictive values of a positive and negative test for relapse was 68%
      and 73%, respectively (specificity 95%). In conclusion, we identified two effects
      by which smoking alters the course of GD. First, smoking is implicated to elevate
      TRAb levels and therefore increase the risk for relapse during follow-up. Second,
      smoking is an independent risk factor to worsen the clinical course of both, GD
      patients with low and high immunological risk to experience relapse after a
      successful outcome of ATDT. Thus, our data suggest that smoking has modifying
      immunological consequences and an adverse impact on the course of GD after
      withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.

PMID- 17039421
TI  - Prevalence of glutamic acid decarboxylase antibody positivity and its association
      with insulin secretion and sensitivity in autoimmune thyroid disease: A pilot
      study.
AB  - OBJECTIVE: Type 1 diabetes and autoimmune thyroid disease are commonly
      associated. Few studies have addressed islet-cell autoimmunity and its relation
      with glucose homeostasis in Hashimoto's thyroiditis. The aims of this study were:
      (1) to determine the prevalence of islet-cell autoimmunity, and (2) to compare
      insulin sensitivity and secretion patterns between normal glucose tolerant
      glutamic acid decarboxylase antibodies (GA-D-Ab) positive and negative patients
      with Hashimoto's thyroiditis. METHODS: Two hundred fifty-three consecutive
      patients with Hashimoto's thyroiditis were recruited. After excluding 38 patients
      with diabetes mellitus, 215 were screened for presence of GAD-Ab. Nine GAD-Ab
      positive and 8 age, sex and body mass index (BMI) matched GAD-Ab negative
      patients from the same cohort were included. Frequently sampled intravenous
      glucose tolerance tests (FSIGTT) were applied. Using glucose and insulin data
      from FSIGTT, fasting glucose to insulin ratio, HOMA-IR and HOMA-beta-cell
      function, using the minimal model analysis (MIN-MOD) program, the first phase
      insulin secretion in response to glucose, the insulin sensitivity index and
      glucose sensitivity index were calculated. RESULTS: Eleven patients were positive
      for GAD-Ab (5.1%). There was no difference in any insulin sensitivity or
      secretion parameters between the GAD-Ab positive and negative patients.
      CONCLUSIONS: Our results suggest that the prevalence GAD-Ab in Hashimoto's
      thyroiditis is around 5%. GAD-Ab antibody positivity per se does not appear to be
      associated with any disturbances in insulin sensitivity or insulin secretion in
      this specific population. The presence of islet-cell autoimmunity does not seem
      to influence insulin secretion or action in normal glucose tolerant subjects with
      Hashimoto's thyroiditis in this pilot study. Whether the presence of GAD-Ab per
      se or along with other antibodies impairs insulin dynamics or predicts the
      development of diabetes in autoimmune thyroiditis remains to be determined in
      future studies.

PMID- 17039422
TI  - Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic
      control and lowers body weight in subjects with type 2 diabetes.
AB  - AIMS: Effects of the long acting GLP-1 analogue--liraglutide in subjects with
      type 2 diabetes. METHODS: 144 type 2 diabetic subjects on metformin treatment
      (1000 mg BID) were randomised to 5 weeks of treatment (double-blind) with
      metformin plus liraglutide, liraglutide or metformin, or metformin plus
      glimepiride (open label). The dose of liraglutide was increased weekly from 0.5
      to 2 mg OD. RESULTS: Liraglutide added to metformin monotherapy was associated
      with a significant reduction in fasting serum glucose (FSG) (-3.9 mM -4.9; -2.9)
      (primary objective), and HbA1c levels (-0.8% -1.2; -0.4). Furthermore,
      liraglutide in combination with metformin vs. metformin plus glimepiride
      significantly reduced FSG (-1.2 mM -2.2; -0.2). In addition, body weight was
      significantly lower in the metformin plus liraglutide vs. the metformin plus
      glimepiride group (-2.9 kg -3.6; -2.1). There were no biochemically confirmed
      episodes of hypoglycaemia with liraglutide treatment. Nausea was the most
      frequently reported adverse event following liraglutide therapy, it was transient
      in nature, and led to withdrawal of only 4% of the subjects. CONCLUSIONS: Using a
      weekly dose-titration liraglutide is well tolerated up to 2 mg daily. While
      liraglutide caused transient gastrointestinal side effects, this rarely
      interfered with continuing treatment. An improvement in FSG over that in control
      groups was seen for liraglutide as an add-on to metformin. In the latter case,
      body weight was reduced in comparison to metformin plus glimepiride. Liraglutide
      is a promising drug for the treatment of type 2 diabetes.

PMID- 17039423
TI  - An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated
      with age at onset of type 2 diabetes mellitus.
AB  - Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions, including
      insulin secretion. An insertion/deletion (I/D) polymorphism of the alpha2B-AR
      gene located on chromosome 2 has recently been described. The aim of the present
      study was to examine if there is a difference in the D allele frequency of
      alpha2B-AR gene between type 2 diabetic patients and controls, as well as to
      ascertain whether the D allele confers an increased risk for earlier onset of
      diabetes. This study included 199 type 2 diabetic patients and 204 age- and sex
      matched healthy volunteers. Genotyping of I/D polymorphism was performed by PCR.
      No significant difference in the D allele frequency was observed between the two
      groups (22.1% vs. 19.1%, p = 0.409). Among type 2 diabetic patients, however,
      presence of the D allele was associated with significantly younger age at onset
      of diabetes (51.4+/-8.6 vs. 59.2+/-9.7 years, p < 0.001). Multiple stepwise
      linear regression identified alpha2B I/D genotype as an independent predictor of
      age at onset of DMT2, explaining 14.3% of its variance. This result indicates
      that the D allele may be implicated in impaired glucose metabolism leading to
      earlier manifestation of diabetes in predisposed subjects.

PMID- 17039424
TI  - Evaluation of the diabetic charcot foot by MR imaging or plain radiography--an
      observational study.
AB  - Magnetic resonance (MR) images and concomitant plain radiographs of 26 Charcot
      feet of different stages (stage 0 to III) were reviewed in retrospect for
      discordant findings. Bone and joint abnormalities were evaluated qualitatively,
      and quantitatively guided by the AO integral classification of injuries of the
      foot. MR images revealed traumatic bone and joint injuries (bone oedema, occult
      fractures, and joint effusion) already in stage 0, when X-ray still showed normal
      bone and joint anatomy (p = 0.02). Moreover, MR images revealed bone oedema,
      joint effusion and soft tissue oedema in addition to fractures and calluses in
      stage I (bone dissolution), stage II (bone coalescence), and stage III (bone
      remodeling), i.e., in stages with overt radiographic pathology. According to this
      observational study, MR imaging, in addition to radiography, provides important
      information as to the extent and the natural course of bone injury in the
      diabetic Charcot foot. MR imaging, thus, may improve disease staging, as well as
      treatment monitoring.

PMID- 17039425
TI  - Evaluation of tight junction protein 1 encoding zona occludens 1 as a candidate
      gene for albuminuria in a Mexican American population.
AB  - Albuminuria, a hallmark of diabetic nephropathy, has been shown to be
      significantly heritable in multiple studies. Therefore, the identification of
      genes that affect susceptibility to albuminuria may lead to novel avenues of
      intervention. Current evidence suggests that the podocyte and slit diaphragm play
      a key role in controlling the selective sieve of the glomerular filtration
      barrier, and podocyte-specific genes have been identified that are necessary for
      maintaining its integrity. We therefore investigated the role of gene variants of
      tight junction protein (TJP1) which encodes another slit diaphragm-associated
      protein zona occludens 1 as risk factors for albuminuria in the San Antonio
      Family Diabetes/Gallbladder Study (SAFDGS), which consists of extended Mexican
      American families with a high prevalence of type 2 diabetes. Albuminuria, defined
      as an albumin (mg/dl) to creatinine (mg/dl) ratio (ACR) of 0.03, which is
      approximately equivalent to a urinary albumin excretion (UAE) >30 mg/day, was
      present in a total of 14.9% of participants, and 31% had type 2 diabetes. The
      TJP1 exons, flanking intronic sequence, and putative proximal promoter regions
      were investigated in this population. Twentynine polymorphisms, including 7
      nonsynonymous SNPs, were identified and genotyped in all subjects of this study
      for association analysis. Three sets of correlated SNPs, which include 3 exonic
      SNPs, were nominally associated with ACR (p value range 0.007-0.049); however,
      the association with the discrete trait albuminuria was not significant (p value
      range 0.094-0.338). We conclude that these variants in TJP1 do not appear to be
      major determinants for albuminuria in the SAFDGS; however, they may play a minor
      role in its severity in this Mexican-American population. Further examination of
      the TJP1 gene region in this and other cohorts will be useful to determine
      whether ZO-1 plays a significant role in glomerular permselectivity.

PMID- 17039426
TI  - Parathyroid hormone (1-34) augments angiopoietin-1 expression in human osteoblast
      like cells.
AB  - Parathyroid hormone (PTH) is a major regulatory factor in skeletal physiology.
      However, the molecular mechanism underlying the effects of PTH on bones has yet
      to be elucidated in detail. Recently, some reports have demonstrated the crucial
      role of bone vasculature with regard to bone density. Angiopoietin-1 (Ang-1),
      along with VEGF, has been established as a primary angiogenic regulatory agent.
      In this study, we have attempted to characterize the effects of PTH (1-34) on Ang
      1 expression and signaling molecules, employing primary-cultured human osteoblast
      like cells. Quiescent osteoblasts were exposed to PTH (1-34), after which Ang-1
      expression was determined at the mRNA and protein levels. Reverse transcription
      polymerase chain reaction (RT-PCR) analyses indicated that Ang-1 mRNA expression
      increased as the result of PTH (1-34) treatment. The expression of the Ang-1
      protein was also augmented as the result of treatment with PTH (1-34). An
      adenylyl cyclase activator, forskolin, was shown to induce Ang-1 mRNA expression,
      whereas the protein kinase A inhibitor, H-89, blocked the PTH (1-34)-mediated
      expression of Ang-1 mRNA. These findings indicate that PTH (1-34)-mediated Ang-1
      expression involves adenylyl cyclase-protein kinase A dependent signaling. Our
      observations also show that Ang-1 may perform a crucial role in the effects of
      PTH (1-34) on bones, possibly involving alterations in bone vasculature.

PMID- 17039427
TI  - Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma
      accompanied by renal infarction.
AB  - Ectopic production of corticotropin-releasing hormone (CRH) by a pheochromocytoma
      is an infrequent cause of Cushing's syndrome. We report the case of a 43-year-old
      man with Cushing's syndrome due to a CRH-producing adrenal pheochromocytoma. The
      patient had clinical and biochemical evidence of hypercortisolism in conjunction
      with high ACTH levels and non-suppressible serum cortisol levels on low-dose and
      high-dose dexamethasone suppression testing. In addition to these clinical
      features of one month's duration, the patient developed symptoms of
      pheochromocytoma including headache, hypertension that was resistant to
      conventional therapy and excessive sweating. Biochemical testing confirmed
      elevated 24-hour urinary catecholamines and metabolites. Abdominal CT revealed a
      4.5 x 4 x 3.5 cm mass in the left adrenal gland. He underwent elective left
      adrenalectomy. Light microscopic and immunochemical studies revealed a
      pheochromocytoma that contained immunoreactive CRH and was negative for ACTH.
      Plasma ACTH and dexamethasone supression tests normalized after surgery. This is
      an unusual case of a CRH-secreting pheochromocytoma. This was complicated by
      renal infarction, illustrating further the complexity of Cushing's syndrome in a
      patient with pheochromocytoma caused by CRH hypersecretion.

PMID- 17039428
TI  - [Federal Cross for Merits to Professor Dr. Friedrich Wilhelm Schwartz].

PMID- 17039429
TI  - [Possibilities for intervention in depression among adolescents and young adults
      from a public health point of view].
AB  - When considering measures to decrease the burden of disease that is caused by
      depression, the depressive diseases of adolescents and young adults are of
      increasing interest. The prevalence in this group is high and an increase in
      prevalence has to be considered. The prognosis for juvenile depression is
      particularly bad. This review discusses the potentials to influence the burden of
      disease through interventions such as therapy, indicated, selective and universal
      prevention and health promotion for adolescents and young adults. The most impact
      can thereby be expected from an effective treatment of depression and other
      mental diseases that have high co-morbidity with depression. There is some
      evidence for the effectiveness of preventive interventions for depression,
      however, most approaches currently seem to be unsuitable for wide implementation
      in the population. However, as open measures, they can offer individual benefit.
      Health promotion that focuses on political, living and societal conditions should
      be directed at the family. Policy measures that improve the living conditions of
      parents also promote the mental health of children. Finally, the discussion about
      the burden of disease that is caused by depression should be held by considering
      current societal norms. In this context, it is of special interest as to how much
      depression and how much loss of function should be still considered as normal and
      not eligible for intervention.

PMID- 17039430
TI  - [Professional status and development of morbidity of health insurance patients in
      the period 1990 to 2003. A longitudinal Analysis of Routine Data from the Gmunder
      Ersatzkasse].
AB  - In Germany there are only insufficient data both with regard to general morbidity
      events as well as with regard to the effects of specific professions on the
      morbidity process. For this reason the data of the Gmuender Ersatzkasse (GEK)
      have been analysed with a longitudinal design for the period 1990 to 2003. Our
      sample includes all employed members of the GEK who had been insured as of
      January 1, 1990 and were between 30 and 59 years old at this baseline. The total
      sample comprises 129,173 men and 13,567 women. The statistical analysis was
      performed with the statistical package "Transitional Data Analysis" (TDA) which
      was developed especially for longitudinal data. The analysis includes both
      cumulated morbidity rates as well as transition rates (Cox regression). The
      analysis shows that the cumulated morbidity rates of the seven diseases are
      higher for women than for men in the age category 30-39 years. In the age
      categories 40-49 and 50-59 years the cumulated morbidity rates are higher for men
      than for women. With regard to the occupations, the highest morbidity rates are
      found for manual occupations and services without special skills. The lowest
      rates are found for professions with high skills, engineers and managers. The
      results of the longitudinal analysis show distinctive social gradients. For
      occupations with lower skills the morbidity rates are about 100 percent higher
      than those of occupations with higher skills. Longitudinal analyses on the basis
      of health insurance fund data can make an important contribution to the
      monitoring of health and morbidity and should therefore be conducted also by
      other health insurance funds.

PMID- 17039431
TI  - [Psychosocial workload, sick leave, and health-related well being: an empirical
      study from the perspective of gender research].
AB  - PURPOSE: The aim of this study was to test hypotheses on the consequences of
      gender role expectations with regard to the extent of work stress, selected
      health-related measures and their associations. METHOD: Data on psychosocial
      workload (questionnaire of effort-reward imbalance), sick leave (self-reports of
      the duration of medically certified sick leave during the past two years) and
      health-related well being were collected in a representative sample of German
      full-time employees (n = 666). Hypotheses were tested using analyses of variance
      (ANOVA) and covariance (ANCOVA) and moderated linear regression analyses.
      RESULTS: Women reported lower health-related well-being as compared to men while
      effort-reward imbalance and sick leave did not differ between the sexes. Parents
      reported slightly longer durations of sick leave during the past two years than
      childless participants (not significant). The results of stratified linear
      regression analyses show stronger associations between effort-reward imbalance
      and both health-related measures for women with children than for men with
      children, while single men and women do not differ in this regard. CONCLUSIONS:
      Evidence of this kind can be useful for the purposeful planning and
      implementation of health promotion measures at work. Women with children would be
      a group deserving special attention. The findings also point to continuing
      differences in gender role expectations in the family context.

PMID- 17039432
TI  - [Working hours and job satisfaction among physicians in hospitals and general
      practice in Munich. Results of an anonymous questionnaire].
AB  - PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis-
      und Bezirksverband Munchen) performed a survey among employed physicians in
      Munich on working hours and working conditions. The aim of the study was to
      assess the extent to which the German law on working hours is actually
      implemented in employed physicians, and to obtain information about their work
      satisfaction. METHODS: A questionnaire was sent to all employed physicians in
      hospitals and medical practices. Participants were asked to give anonymous
      information and send it back per mail. RESULTS: In total, 2450 out of 5461
      physicians took part in the survey. 45% reported that their working hours do not
      meet the German law on working hours of 1994. 44.4% stated that overtime is not
      fully recognized by their employers. 43.5% think the job would become more
      attractive if the law was implemented. 63.3% expect an income loss with the
      implementation. 53.7% are thinking about quitting their job. For 59.9% the burden
      of long working hours is an important reason for this. Women are more likely to
      be given a limited employment contract than men, and their overtime is more
      rarely recognized in full. CONCLUSION: Many employed physicians in Munich are
      dissatisfied with their job. The high burden of long working hours is a main
      reason for this.

PMID- 17039433
TI  - [Efficacy of an intervention programme on burnout symptoms of partners of
      depressed patients].
AB  - AIM OF THE STUDY: A newly developed group intervention programme was evaluated
      with regard to its effectiveness to decrease the burnout symptoms of the partners
      of depressed patients. METHODS: Within a period of six months, a group of 66
      persons has taken part in the intervention for a total of twelve group sessions.
      A control group consisted of 50 persons without any intervention. Burnout was
      assessed using the German version of the Maslach Burnout Inventory (MBI). To
      evaluate the time effect, the burnout dimensions were used as independent
      variables in random effects models. RESULTS: Over the analyzed period of time no
      significant positive effect was measured on any of the assessed burnout
      dimensions. CONCLUSIONS: An increased inclusion of depressed patients in the
      intervention as well as an increased intensity and a lowering of the admission
      threshold for the heavily burdened relatives could increase the effectiveness of
      the program.

PMID- 17039434
TI  - [Regional mortality differences in Bavaria].
AB  - OBJECTIVE: In completion of a decision of the Bavarian Parliament we examined the
      regional mortality differences within Bavaria. DATA: The analysis was based on
      the number of deaths in Bavaria in the years of 2000-2002. Data on regional
      demographic and socioeconomic indicators were used to identify potential
      associations. METHODS: Deaths were analysed by cause of death and region. Crude
      and age standardised mortality rates were calculated. Additionally, we assessed
      the potential years of life lost in order to obtain some indication of the
      potential effects of preventive action. The association with likely explanatory
      factors was investigated on an ecological level. RESULTS: The regional mortality
      differences in Bavaria show a northeast-southwest gradient favouring the
      southwest, which reflects the socioeconomic situation within Bavaria. This may be
      due to the economic disadvantage northeast Bavaria had to endure as a result of
      its marginal location within a divided Europe. We found strong bivariate
      correlations of the mortality rate with individual socioeconomic factors (e. g.
      with available income: -0.582; with unemployment: +0.416; with the immigration
      rate: -0.473). Exploratory analysis suggest that about 50 % of the regional
      variation in mortality could be explained by socioeconomic factors. DISCUSSION:
      The results for cause of death indicate that behavioural factors in relation to
      socioeconomic aspects may well play a role in the mortality gradient. This will
      be the focus of a future piece of research of our unit.

PMID- 17039435
TI  - [How much do inpatient treated diabetics know about their disease?].
AB  - AIM OF STUDY: The aim of the study was to find to find out which factors are able
      to predict the disease-specific knowledge of in-patient diabetic patients and to
      characterize this group of patients. METHODS: The disease-specific knowledge of
      diabetic patients of a Hospital in Munich, Germany (department of diabetology)
      was tested using a general questionnaire and a specific diabetes knowledge test.
      All data manipulation and statistical calculations were conducted with the
      statistical software package SAS (version 9.1). RESULTS: On average type-1
      diabetics achieved 73% of the possible points in the knowledge test, type-2
      diabetics achieved 68% of total points. In bivariate analyses, using logistic
      regression, existence of diabetes related complications was a significant
      predictor of poor knowledge (OR = 4.36; 95%-KI: 1.38-13.77) in type-1-diabetics.
      Other factors, e. g. lack of diabetes education were associated with low test
      results but reached no statistical significance (OR = 6.13; 95%-KI: 0.67-56.42).
      In multivariate logistic regression (female) gender was a significant risk factor
      for low test results (OR = 7.66; 95%-KI: 1.18-49.8). In type-2-diabetics lack of
      diabetes education (OR = 3.86; 95%-KI: 1.51-9.84), low self-assessment of
      information about diabetes (OR = 3.90; 95%-KI: 1.36-11.21) and lack of knowledge
      about diabetes diet (OR = 4.06; 95%-KI: 1.60-10.28) were predictors of poor test
      results. The existence of diabetes related complications was associated with poor
      test results but showed no statistical significance in multivariate analysis (OR
      = 2.99; 95%-KI: 0.85-10.43). CONCLUSIONS: There is a group of diabetic inward
      patients that is less informed about diabetes and shows knowledge deficits in
      testing. These patients often lack diabetes education and show an unfavourable
      course of the disease, already having diabetes related complications. Type-2
      diabetes patients who feel that they have poor information about their disease
      actually achieve lower results in knowledge testing. Efforts to assure diabetes
      education for these patients are essentially necessary.

PMID- 17039436
TI  - [Smoking behavior in adolescents: a comparison of population-representative,
      regional or selectively assessed data and implications for prevention].
AB  - INTRODUCTION: The prevalence of adolescent smoking underlines the necessity of
      preventive measures, which goals are based on representative data. It is not
      known whether schools participate in prevention interventions, where smoking
      constitutes a relatively big or minor problem. OBJECTIVE: This study examines a
      population of adolescents on (a) different smoking variables and (b) compares
      them with representative, population based data. METHODS: Survey of n = 324
      adolescents of grade 7-10 in 3 schools in Greifswald and surroundings that were
      ready to participate in a prevention curriculum. RESULTS: In total, 80% of the
      students under examination indicated to have at least tried smoking in their
      lifetime. Daily smokers were 31%, 18% were occasional smokers, 39% have indicated
      that they hat tried to quit without success. These figures vary across age, grade
      and sex. Smoking prevalence is comparable between schools ready to participate in
      prevention and regionally assessed data, but much higher than population based
      data would have estimated. CONCLUSION: The goal of preventive measures can not be
      solely grounded on representative, population-based data, but needs (a) to be
      regionally defined and (b) to consider the population actually participating in
      such prevention interventions. The readiness to participate is not higher in
      schools where smoking constitutes a comparable minor problem. Preventive measures
      are applied in schools where the problem is perceived.

PMID- 17039437
TI  - [The spread of HIV/AIDS in Ukraine].
AB  - BACKGROUND: In the end-year report 2004 of the European Centre for the
      Epidemiological Monitoring of AIDS (EuroHIV), the number of newly diagnosed HIV
      infections in Ukraine ranks second in the WHO European Region after the Russian
      Federation. METHODS: An analysis of the HIV/AIDS reports from the official
      epidemiological register of the Ukrainian Centre for AIDS Prevention between 1987
      and 2005 was undertaken. In addition, reports from the seroepidemiological
      monitoring were utilised. RESULTS: According to the Ukrainian Ministry of Health,
      the cumulative number of reported HIV infections by the end of 2005 amounts to
      more than 88,900 cases with 13,786 new reports in 2005. The number of newly
      registered AIDS cases rose from 45 in 1995 to 4220 in 2005. However, because of
      many unreported HIV diagnoses, the actual numbers are presumed to exceed the
      official reports considerably. Most of the infections are associated with
      injection drug abuse. The second most important route of transmission is sexual
      contact, also due to an increase in commercial sex. Vertical transmissions from
      infected mothers to their children rank third. CONCLUSION: HIV was not a
      significant problem in the Ukraine before 1995. Since 1995 there has been a
      considerable increase in the number of newly registered HIV cases. At the
      beginning of the epidemic, HIV was mainly transmitted through sexual contacts in
      the Ukraine. Since 1995 infected drug users have been the main source of
      infection in the spread of the epidemic. Unless effective preventive measures are
      taken, and unless there is more investment in development projects, the HIV/AIDS
      epidemic in Ukraine could also affect the health system in neighbouring European
      countries.

PMID- 17039438
TI  - [Associations between bioaerosols coming from livestock facilities and asthmatic
      symptoms in children].
AB  - Although health effects of occupational exposures to livestock emissions are
      known, potential associations between living in the neighbourhood of intensive
      livestock facilities and the risk of developing respiratory or allergic diseases
      are still under discussion. During routine school entry examinations in selected
      rural districts in Lower Saxony we asked parents about respiratory and allergic
      symptoms of their 5-6 year old children. A questionnaire with standardised
      questions of the ISAAC-Studies for respiratory and allergic symptoms and
      corresponding risk factors was used. Complementarily the children were examined
      for visible signs of flexural dermatitis and in a subsample the SX1-test was used
      as an in vitro test for inhalative IgE mediated sensibilisations in capillary
      blood. Individual exposure to bioaerosols (endotoxin, fungi, bacteria and total
      dust) coming from livestock facilities was estimated using a Lagrange dispersion
      model based on the emission rates and locations of the lifestock facilities. A
      total of 7943 questionnaires (response rate over 85%) were analysed, of which
      3867 could be used for the correlation analyses between exposition to endotoxin
      and asthmatic symptoms. Multivariate logistic regression models were analyzed,
      considering an atopic disease of the parents as a potential effect modifier and
      not as a confounder. The prevalence of allergic and asthmatic symptoms is similar
      to the results of other comparable studies, e. g. "wheezing in the last 12
      months" 15.9% for boys and 12.9% for girls. An increase in the prevalence of
      asthmatic symptoms for higher endotoxin levels was observed only for children of
      atopic parents. The multivariate controlled odds ratio for one unit logarithm
      endotoxin concentrations is 1.15, p-value 0.016. Similar effects were observed
      for other asthma indicators, but not for subjective criteria of the exposition,
      e. g. the distance to the next large livestock facility guesstimated by parents.
      Among the overall analysed potential associations between exposition to
      bioaerosols and asthmatic and allergic symptoms only a few were statistically
      significant. The discussed association between endotoxin and asthmatic symptoms
      in predisposed children needs further investigation.

PMID- 17039440
TI  - Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on
      and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel,
      prevent attachment, and kill adult Ixodes scapularis and Amblyomma americanum
      ticks on dogs.
AB  - This study evaluated the effectiveness of two topical spot-on formulations --
      imidacloprid(8.8% w/w)-permethrin (44.0% w/w) and fipronil (9.8% w/w)-(S)
      methoprene (8.8% w/w)--to repel, prevent the attachment of, and kill adult Ixodes
      scapularis and Amblyomma americanum on dogs. Twelve purpose-bred beagles were
      distributed into three groups of four dogs each; one group served as untreated
      controls, and each of the other two groups received one of the test products.
      Dogs were exposed to 25 adult ticks of each species for 10 minutes on
      posttreatment days 3, 7, 14, 21, and 28. Unattached or repelled ticks were
      collected and evaluated for viability, and on-dog tick counts were conducted at
      3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation
      provided significant repellency against I. scapularis for up to 3 weeks after
      treatment, and both formulations provided good overall control of I. scapularis
      and A. americanum during the study period.

PMID- 17039441
TI  - Evaluation of an imidacloprid (8.8% w/w)--permethrin (44.0% w/w) topical spot-on
      and a fipronil (9.8% w/w)--(S)-methoprene (8.8% w/w) topical spot-on to repel,
      prevent attachment, and kill adult Rhipicephalus sanguineus and Dermacentor
      variabilis ticks on dogs.
AB  - This study evaluated the effectiveness of two topical spot-on formulations,
      imidacloprid (8.8% w/w)--permethrin (44.0% w/w) and fipronil (9.8% w/w)--(S)
      methoprene (8.8% w/w), to repel, prevent the attachment of, and kill adult
      Rhipicephalus sanguineus and Dermacentor variabilis on dogs. Twelve purpose-bred
      beagles were distributed into three groups of four dogs each; one group served as
      untreated controls and each of the other two groups received one of the test
      products. Dogs were exposed to 25 adult ticks of each species for 10 minutes on
      posttreatment days 3, 7, 14, 21, and 28. Nonattached or repelled ticks were
      collected and evaluated for viability, and on-dog tick counts were conducted at
      3, 24, and 48 hours after tick exposure. The imidacloprid-permethrin formulation
      provided significant repellency of R. sanguineus and D. variabilis for up to 3
      and 4 weeks after treatment, respectively; and provided good overall control for
      R. sanguineus and D. variabilis during the study period. The fipronil--(S)
      methoprene formulation provided good overall tick control during the study
      period.

PMID- 17039442
TI  - Prevalence of Giardia in symptomatic dogs and cats throughout the United States
      as determined by the IDEXX SNAP Giardia test.
AB  - National prevalence of Giardia infection in dogs and cats presenting to clinics
      with vomiting and/or diarrhea was examined using the IDEXX SNAP Giardia test kit.
      Veterinary practices across the United States were sent an invitation to
      participate in the survey and asked to use the test on fecal samples from the
      target population. The survey requested that the clinics report the results of 20
      or more tests. A total of 21,092 results were reported, comprised of 16,114 dogs
      and 4,978 cats. Analysis of the data (excluding the handful of results reported
      from Puerto Rico) showed a Giardia prevalence of 15.6% among dogs tested, and
      10.8% among cats. This difference was statistically significant (p < 0.001).
      Regional categorization into Northeast, Southeast, West, and Midwest drew out
      significant (p < 0.001) differences in prevalence in most cases for dogs; the
      differences were not significant for cats. These differences and other variables
      are currently being examined with this and additional data sets. We conclude on
      the basis of the SNAP test diagnostic that Giardia is a common enteric agent
      among dogs and cats with gastrointestinal signs.

PMID- 17039443
TI  - Comparison of sevoflurane and isoflurane in domestic ferrets (Mustela putorius
      furo).
AB  - Isoflurane anesthesia is commonly used in ferrets for routine examinations and
      diagnostics. Sevoflurane is now being used as well, but there have been no
      studies to date directly comparing these agents in domestic ferrets. A
      prospective study was designed to evaluate the quality and speed of anesthetic
      induction and recovery using isoflurane and sevoflurane in ferrets. In addition
      effects on heart rate, blood pressure and packed cell volume were also recorded.
      No significant differences were noted between anesthetic agents.

PMID- 17039444
TI  - Three-year duration of immunity in cats following vaccination against feline
      rhinotracheitis virus, feline calicivirus, and feline panleukopenia virus.
AB  - Forty-two seronegative cats received an initial vaccination at 8 weeks of age and
      a booster vaccination at 12 weeks. All cats were kept in strict isolation for 3
      years after the second vaccination and then were challenged with feline
      calicivirus (FCV) or sequentially challenged with feline rhinotracheitis virus
      (FRV) followed by feline panleukopenia virus (FPV). For each viral challenge, a
      separate group of 10 age-matched, nonvaccinated control cats was also challenged.
      Vaccinated cats showed a statistically significant reduction in virulent FRV
      associated clinical signs (P = .015), 100% protection against oral ulcerations
      associated with FCV infection (P < .001), and 100% protection against disease
      associated with virulent FPV challenge (P < .005). These results demonstrated
      that the vaccine provided protection against virulent FRV, FCV, and FPV challenge
      in cats 8 weeks of age or older for a minimum of 3 years following second
      vaccination.

PMID- 17039445
TI  - Three-year rabies duration of immunity in dogs following vaccination with a core
      combination vaccine against canine distemper virus, canine adenovirus type-1,
      canine parvovirus, and rabies virus.
AB  - Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live
      canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine
      parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV,
      and killed rabies virus vaccine. An additional 31 seronegative pups served as age
      matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years
      after receiving the second vaccination and then were challenged with virulent
      rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32
      vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies
      infection. These study results indicated that no immunogenic interference
      occurred between the modified-live vaccine components and the killed rabies virus
      component. Furthermore, these results indicated that the rabies component in the
      test vaccine provided protection against virulent rabies challenge in dogs 12
      weeks of age or older for a minimum of 3 years following vaccination.

PMID- 17039446
TI  - Enrofloxacin use in a long-distance transport model of equine respiratory
      disease.
AB  - Successful clinical management of bacterial pneumonia in horses depends on the
      administration of an appropriate antimicrobial agent at an adequate dosage and
      frequency, given by the correct route of administration for an adequate duration.
      Empiric antimicrobial therapy should be based on the clinician's experience and
      current veterinary literature. Based on the frequency of Gram-positive bacterial
      pathogens isolated from horses with bacterial pneumonia, every effort should be
      made to provide antimicrobial coverage for this class of pathogens. Gram-negative
      pathogens may co-exist; therefore, broad spectrum antimicrobial coverage may be
      necessary. Antimicrobial agents posing potential drug related risks (e.g.
      nephrotoxicity in dehydrated patients, peracute colitis in racehorses) may not be
      appropriate for empiric use and enrofloxacin offers an enhanced spectrum of
      antimicrobial activity with reduced risk of complication. Our findings indicate
      that in cases of exclusive Gram-positive respiratory disease, solo therapy with
      enrofloxacin is not indicated.

PMID- 17039447
TI  - A comparison of N-butylscopolammonium and lidocaine for control of rectal
      pressure in horses.
AB  - In its FDA approved formulation, N-butylscopolammonium bromide (Buscopan
      Injectable Solution, Boehringer Ingelheim Vetmedica) is an anticholinergic
      spasmolytic agent indicated for management of abdominal pain associated with
      spasmodic colic, flatulent colic, and simple impactions in horses. Use of this
      drug ablates gastrointestinal peristalsis and rectal pressure. It ahs been
      suggested that N-butylscopolammonium bromide could be used to facilitate rectal
      examinations in horses. This study compared the effects of N-butylscopolammonium
      bromide versus lidocaine and a saline control on rectal pressure and the number
      of rectal strains during rectal examination. The results of this study indicate
      that this drug increases the quality and, presumably, the safety of rectal
      examinations in horses.

PMID- 17039448
TI  - Evaluation of the efficacy provided by a Recombinant Canarypox-Vectored Equine
      West Nile Virus vaccine against an experimental West Nile Virus intrathecal
      challenge in horses.
AB  - Efficacy of the Recombitek Equine West Nile Virus (WNV) vaccine was evaluated
      against a WNV intrathecal challenge model that results in WNV-induced clinical
      disease. Ten vaccinated (twice at days 0 and 35) and 10 control horses were
      challenged 2 weeks after administration of the second vaccine with a virulent WNV
      by intrathecal administration. After the challenge, eight of 10 controls
      developed clinical signs of encephalomyelitis whereas one vaccinate exhibited
      muscle fasciculation only once. Nine controls and one vaccinate developed a
      fever. Histopathology revealed mild to moderate nonsuppurative encephalitis in
      eight controls and one vaccinate. None of the vaccinates and all of the controls
      developed WNV viremia after challenge. All vaccinated horses developed antibodies
      to WNV after vaccination. These and results of previous studies demonstrate
      efficacy of the Recombitek WNV vaccine against WNV-induced clinical disease and
      natural challenge with WNV-infected mosquitoes.

PMID- 17039449
TI  - An evaluation of the metaphylactic effect of ceftiofur crystalline free Acid in
      feedlot calves.
AB  - The relative effect of metaphylactic ceftiofur crystalline free acid (CCFA)
      versus metaphylactic tilmicosin was evaluated in beef calves under commercial
      feedlot conditions in Nebraska. At feedlot arrival, 11,605 animals at ultrahigh
      risk of developing bovine respiratory disease (BRD) were allocated to one of
      three experimental groups: CCFA-3 (6.6 mg/kg SC), CCFA-7 (6.6 mg/kg), or TILM-3
      (tilmicosin, 10 mg/kg SC). Animals were eligible for subsequent BRD treatment 3
      (CCFA-3 and TILM-3 groups) or 7 (CCFA-7 group) days later. Compared with the TILM
      3 group, overall chronicity, overall mortality, BRD mortality, and metabolic
      mortality rates were significantly (P < .05) lower in the CCFA-3 and CCFA-7
      groups; average daily gain was significantly (P < .05) higher in the CCFA-3
      group; the proportion of quality grade No Roll carcasses was significantly (P <
      .05) lower in the CCFA-3 and CCFA-7 groups; and there were per-animal advantages
      of 22.05 dollars and 18.98 dollars in the CCFA-3 and CCFA-7 groups, respectively.
      In beef calves at ultrahigh risk of developing BRD, it is more cost effective to
      administer metaphylactic CCFA than tilmicosin at feedlot arrival.

PMID- 17039450
TI  - Evaluation of the efficacy of a modified-live combination vaccine against
      abortion caused by virulent bovine herpesvirus type 1 in a one-year duration-of
      immunity study.
AB  - This study demonstrated that a multivalent vaccine containing modified-live
      bovine herpesvirus type 1 (BHV-1) protected pregnant heifers and their fetuses
      against virulent BHV-1 challenge exposure at 365 days after vaccination. The
      percentage of abortions or fetal deaths caused by BHV-1 was significantly higher
      in control heifers (10 of 10 [100.0%]) than BHV-1-vaccinated heifers (three of 19
      [15.8%]).

PMID- 17039451
TI  - Evaluation of the efficacy of a modified-live combination vaccine against bovine
      viral diarrhea virus types 1 and 2 challenge exposures in a one-year duration-of
      immunity fetal protection study.
AB  - This study demonstrated that the modified-live bovine viral diarrhea virus (BVDV)
      type 1 and 2 fractions of a multivalent vaccine protected pregnant heifers and
      their fetuses against virulent BVDV types 1 and 2 challenge exposures at 370 days
      after vaccination. All BVDV vaccinated heifers inoculated with either BVDV type 1
      or 2 at approximately 62 to 94 days of gestation delivered fetuses or calves that
      were negative for BVDV by ear-notch immunohistochemistry and virus isolation and
      serum neutralization on a prenursing serum sample. In comparison, eight of nine
      and 10 of 10 fetuses or calves from non-BVDV-vaccinated heifers were considered
      persistently infected following exposure to BVDV type 1 and type 2, respectively.

PMID- 17039452
TI  - Fetal protection following exposure to calves persistently infected with bovine
      viral diarrhea virus type 2 sixteen months after primary vaccination of the dams.
AB  - This study demonstrated that the bovine viral diarrhea virus (BVDV; types 1 and
      2) fractions of a multivalent vaccine protected pregnant heifers and their
      fetuses at 149 to 217 days of gestation against exposure to calves persistently
      infected with BVDV type 2a. Eighty percent (eight of 10) of the control heifers
      were viremic at least 1 day following challenge, whereas all (20 of 20) BVDV
      vaccinated heifers were virus isolation-negative on all postchallenge assessment
      days. Ninety percent (nine of 10) of the calves born to control heifers but only
      5% (one of 20) of calves born to BVDV-vaccinated heifers seroconverted to BVDV
      type 2 before ingesting colostrum. One calf born to a control heifer was
      persistently infected. No calves from BVDV-vaccinated heifers were persistently
      infected.

PMID- 17039454
TI  - Efficacy of enrofloxacin against severe experimental Anaplasma marginale
      infections in splenectomized calves.
AB  - Four Anaplasma marginale-infected splenectomized calves with greater than 25%
      parasitized erythrocytes received enrofloxacin at 12.5 mg/kg SC twice, 48 hours
      apart. Two infected splenectomized calves were designated as untreated controls.
      A precipitous decline in percent parasitized erythrocytes from 39.13% to less
      than 1% was observed over 12 days following treatment. However, a self-limiting
      recrudescence of A. marginale parasites was observed within 30 days after
      treatment. Untreated control calves became moribund and were euthanized. These
      data indicate that the regimen of enrofloxacin tested herein ameliorates, but
      does not eliminate, A. marginale infections in splenectomized calves.

PMID- 17039453
TI  - Use of a modified-live vaccine to prevent persistent testicular infection with
      bovine viral diarrhea virus.
AB  - A commercial vaccine containing modified-live bovine viral diarrhea virus (BVDV;
      types 1 and 2) was administered to one group of 22 peripubertal bulls 28 days
      before intranasal inoculation with a type 1 strain of BVDV. A second group of 23
      peripubertal bulls did not receive the modified-live BVDV vaccine before
      intranasal inoculation. Ten of 23 unvaccinated bulls--but none of the vaccinated
      bulls--developed a persistent testicular infection as determined by
      immunohistochemistry and polymerase chain reaction. Results of this study
      indicate that administration of a modified-live vaccine containing BVDV can
      prevent persistent testicular infection if peripubertal bulls are vaccinated
      before viral exposure.

PMID- 17039455
TI  - Induction of cell apoptosis in 3T3-L1 pre-adipocytes by flavonoids is associated
      with their antioxidant activity.
AB  - Obesity is biologically characterized at the cellular level by an increase in the
      number and size of adipocytes differentiated from fibroblastic pre-adipocytes in
      adipose tissue. In this study, we focused on the relationship between the
      influence of flavonoids on cell population growth and their antioxidant activity.
      The results showed that the inhibition of flavonoids (naringenin, rutin,
      hesperidin, resveratrol, naringin and quercetin) on 3T3-L1 pre-adipocytes was
      28.3, 8.1, 11.1, 33.2, 5.6 and 71.5%, respectively. In oxygen radical absorbance
      capacity (ORAC) assay, quercetin had the highest ORAC(ROO) value among the six
      flavonoids tested. Apoptosis assays showed that quercetin increased apoptotic
      cells in time- and dose-dependent manner. Treatment of cells with quercetin
      decreased the mitochondrial membrane potential in the courses of time and dose.
      The cell apoptosis/necrosis assay showed that quercetin increased the number of
      apoptotic cells, but not necrotic cells. Quercetin treatment of cells caused a
      significant time- and dose-dependent increase in the caspase-3 activity. Western
      analysis indicated that treatment of quercetin markedly down-regulated PARP and
      Bcl-2 proteins, and activated caspase-3, Bax, and Bak proteins. These results
      indicate that quercetin efficiently inhibits cell population growth and induction
      of apoptosis in 3T3-L1 pre-adipocytes.

PMID- 17039456
TI  - Visualization of astaxanthin localization in HT29 human colon adenocarcinoma
      cells by combined confocal resonance Raman and fluorescence microspectroscopy.
AB  - Astaxanthin, a carotenoid found in plants and seafood, exhibits
      antiproliferative, antioxidant and anticarcinogenic properties. We show that
      astaxanthin delivered with tetrahydrofuran is effectively taken up by cultured
      colon adenocarcinoma cells and is localized mostly in the cytoplasm as detected
      by confocal resonance Raman and broad-band fluorescence microspectroscopy image
      analysis. Cells incubated with beta-carotene at the same concentration as
      astaxanthin (10 microM) showed about a 50-fold lower cellular amount of beta
      carotene, as detected by HPLC. No detectable Raman signal of beta-carotene was
      found in cells, but a weak broad-band fluorescence signal of beta-carotene was
      observed. beta-Carotene, like astaxanthin, was localized mostly in the cytoplasm.
      The heterogeneity of astaxanthin and beta-carotene cellular distribution in cells
      of intestinal origin suggests that the possible defense against reactive
      molecules by carotenoids in these cells may also be heterogeneous.

PMID- 17039457
TI  - Efficacy and food safety considerations of poultry competitive exclusion
      products.
AB  - Competitive exclusion (CE) products are anaerobic cultures of bacteria that are
      applied to poultry hatchlings to establish a protective enteric microbiota that
      excludes intestinal colonization by human food-borne pathogens. For safety of the
      poultry flock and human consumers, the identities of bacteria in CE products need
      to be known. A CE product is a culture of intestinal contents from adult
      chickens. It may be microbiologically defined by analysis of bacteria isolated
      from the culture, but many bacteria are hard to reliably isolate, identify, and
      characterize with conventional techniques. Sequence analysis of 16S ribosomal RNA
      (rRNA) genes may be more reliable than conventional techniques to identify CE
      bacteria. Bacteria in CE products may contain antimicrobial drug resistance and
      virulence mechanisms that could be transferred to the enteric bacteria of the
      food animal and to the human consumer. Detection methods for specific
      antimicrobial drug resistance and virulence genes and the integrase genes of
      conjugative transposons, mostly utilizing PCR technology, are being developed
      that can be applied to assess these risks in CE bacteria. With improvements in
      efficacy, bacterial identification, and detection and control of the possible
      risks of gene transfer, CE product technology can be made a more effective food
      safety tool.

PMID- 17039458
TI  - Total antioxidant capacity of spices, dried fruits, nuts, pulses, cereals and
      sweets consumed in Italy assessed by three different in vitro assays.
AB  - With the aim to expand the Italian total antioxidant capacity (TAC) database, the
      TAC values of 11 spices, 5 dried fruits, 7 sweets, 18 cereal products, 5 pulses,
      and 6 nuts were determined using three different assays and considering the
      contribution of bound antioxidant compounds in fiber-rich foods (i. e. cereals,
      legumes, and nuts). Among spices, saffron displayed the highest antioxidant
      capacity, whereas among dried fruits, prune exhibited the highest value. The TAC
      values of all the chocolates analyzed were far higher than the other sweet
      extracts measured. Among cereal products, whole meal buckwheat and wheat bran had
      the greatest TAC. Among pulses and nuts, broad bean, lentil and walnuts had the
      highest antioxidant capacity, whereas chickpeas, pine nuts and peanuts were less
      effective. The contribution of bound phytochemicals to the overall TAC was
      relevant in cereals as well as in nuts and pulses. The complete TAC database
      could be utilized to properly investigate the role of dietary antioxidants in
      disease prevention.

PMID- 17039459
TI  - Free radical scavenging and cytoprotective activities of phenolic antioxidants.
AB  - The free radical scavenging activities of three flavonoids (quercetin, rutin and
      catechin) and four hydroxycinnamic acids (caffeic, ferulic, sinapic, and
      chlorogenic acids) were evaluated using both oxygen radical absorbance capacity
      (ORAC) and lipid peroxidation inhibition capacity (LPIC) assays. The
      cytoprotective effects of these compounds were also measured by the degree of
      protection against H(2)O(2)-induced damage of human Jurkat cells. All compounds
      exhibited protection against H(2)O(2)-mediated cytotoxicity in a dose-dependent
      manner. The concentrations required to result in a 50% reduction in cell death
      (EC(50) value) were calculated from their dose-response curves. These ranged from
      0.15-2.65 microM. Overall, the four hydroxycinnamic acids tested were less
      effective than the three flavonoids, and of all compounds tested, quercetin
      offered the strongest protection against H(2)O(2)-induced cell death. A
      comparison of the results showed that the ability to inhibit peroxidation of
      lipids in a liposomal system (LPIC) correlated well with the cytoprotective
      activities (EC(50)), but not with the ability to protect an aqueous fluorescent
      substrate in the ORAC assays. The results suggest that the behavior of
      antioxidants in a liposomal membrane is to some extent similar to the mechanism
      involved in the protection of living cells from oxidative damage.

PMID- 17039460
TI  - Human rectal mucosal gene expression after consumption of digestible and non
      digestible carbohydrates.
AB  - The effect of regular consumption of the low-digestible and prebiotic isomalt
      versus the digestible sucrose on gene expression in rectal mucosa was examined in
      a randomized double-blind crossover trial. Nineteen healthy volunteers received
      30 g isomalt per day or 30 g sucrose as part of a controlled diet over two 4-week
      test periods with a 4-week washout period in between. At the end of each test
      phase rectal biopsies were obtained. After RNA extraction mucosal gene expression
      was assayed using GeneChip microarrays. In addition, expression of cathelicidin
      hCap18/LL37, cellular detoxification enzymes GSTpi, UGT1A1 and CYP3A4,
      cyclooxygenase 2 and barrier factors MUC2 and ZO-1 were determined by real-time
      RT-PCR. Microbiological analyses of fecal samples revealed a shift of the gut
      flora towards an increase of bifidobacteria following consumption of the diet
      containing isomalt. Isomalt consumption did not affect rectal mucosal gene
      expression in microarray analyses as compared to sucrose. In addition, the
      expression of cathelicidin LL37, GSTpi, UGT1A1, CYP3A4, COX-2, MUC2 and ZO-1 was
      not changed in rectal biopsies. We conclude that gene expression of the human
      rectal mucosa can reliably be measured in biopsy material taken at endoscopy.
      Dietary intervention with the low digestible isomalt compared with the digestible
      sucrose did not affect gene expression in the lining rectal mucosa.

PMID- 17039461
TI  - Recent development of small molecular specific inhibitor of protein tyrosine
      phosphatase 1B.
AB  - Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play
      essential roles in intracellular signal transduction by regulating the cellular
      level of tyrosine phosphorylation to control cell growth and differentiation,
      metabolism, cell migration, gene transcription, ion-channel activity, immune
      response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine
      phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many
      human diseases, including cancer, diabetes, and obesity. Therefore, small
      molecular inhibitors of PTP1B can be promising drug candidates. Because of the
      structural homologies in many families of PTPs, it is a challenging task to find
      inhibitors specific to each PTP. Recent studies suggested that secondary binding
      pockets or peripheral binding sites around the conserved active site should be
      exploited to design novel potent and selective PTP1B inhibitors. In this review,
      we discuss the structural and biological features of small molecular PTP1B
      specific inhibitors, with particular emphasis on small molecular inhibitors
      targeting PTP1B over the other PTPs that have been synthesized in the past 4
      years.

PMID- 17039462
TI  - Effect of urethral compliance on the steady state p-Q relationships assessed with
      a mechanical analog of the male lower urinary tract.
AB  - AIMS: Using a lumped parameter theoretical model of bladder outlet function, we
      previously explored the relationship between the tube law of the urethra and the
      pressure-flow characteristics during micturition [Mijailovich et al., 2004]. To
      validate this theoretical model, we constructed a mechanical analog of the male
      lower urinary tract that incorporated elements simulating all relevant parameters
      of the theoretical model. In addition, we determined the effect of alterations in
      compliance of the flow-controlling zone on these relationships. METHODS: In the
      mechanical analog, the bladder neck and urethra were represented by a thin-walled
      conduit made of latex rubber and the prostate with a fluid filled cuff of
      variable compliance encircling the conduit. We measured in the same system steady
      state pressure-flow (p-Q) and pressure-area (p-A) relationships of the flow
      controlling zone. The effects of bladder outlet obstruction and prostatic
      compliance on these relationships were simulated by varying cuff pressure and
      capacitative coupling of the cuff, respectively. RESULTS: We demonstrated two
      previously described flow regimes-critical for low Q, and subcritical for higher
      Q. In the critical flow regime, the cross-sectional area of the collapsible
      conduit downstream of the cuff became narrow up to a site where the area suddenly
      expanded (elastic jump). Pressure losses across the cuff region decreased with
      increasing Q as the elastic jump approached the cuff, and the jump vanished when
      Q became subcritical. By altering prostatic cuff compliance and cuff pressure, we
      showed that an increase in opening pressures was associated with a steeper p-Q
      relationship. CONCLUSIONS: Using this mechanical analog, the measurements of p-A
      and p-Q relationships under various experimental conduit conditions validated our
      previous theoretical model of the male lower urinary tract. Both the experimental
      measurements and our previous theoretical model predictions indicate that an
      increase in opening pressure is associated with an increase in the slope of the p
      Q relationship which becomes steeper with decreased cuff compliance. These data
      are in accordance with urodynamic findings in patients with benign prostatic
      hypertrophy (BPH) and suggest that a reduction in prostatic compliance
      exacerbates the severity of obstruction.

PMID- 17039463
TI  - Use of fetal magnetic resonance imaging in differentiating ileal atresia from
      meconium ileus.

PMID- 17039464
TI  - Lack of human muscle architectural adaptation after short-term strength training.
AB  - The mechanisms governing the increases in force production in response to short
      periods of strength training have yet to be fully elucidated. We examined whether
      muscle architectural adaptation was a contributing factor. Ultrasound imaging
      techniques were used to measure quadriceps muscle architecture at 17 sites in
      vivo in trained and untrained legs of men and women after 2.5 and 5 weeks of
      unilateral knee extension training, as well as in a nontraining control group.
      Despite increases in knee extensor strength of the trained and untrained (women
      only) legs, there were no changes in muscle thickness, fascicle angle, or
      fascicle length in any of the muscles tested. The moderate correlation between
      vastus lateralis thickness (middle site) and eccentric (r = 0.55; P < 0.05) and
      concentric (r = 0.46; P < 0.1) torque after, but not before, training is
      suggestive of neural rather than architectural adaptations predominating in the
      early phase of training.

PMID- 17039465
TI  - Development of novel poly(ethylene glycol)-based vehicles for gene delivery.
AB  - The purpose of this research was to develop and characterize a gene delivery
      vehicle with a poly(ethylene glycol) (PEG) backbone with the aim of overcoming
      limitations, such as cytotoxicity and rapid clearance, associated with current
      commonly used non-viral carriers. PEG was functionalized with DNA-binding
      peptides (DBPs) to make a vehicle (DBP-PEG) capable of condensing DNA. Complexes
      of plasmid DNA and DBP-PEG were formed and characterized by measuring particle
      size, zeta potential, and transfection efficiency as a function of N:P charge
      ratios (DBP-PEG amino groups:DNA phosphate). Dynamic light scattering showed that
      DBP-PEG was able to condense DNA efficiently resulting in a population of
      particles in the range of 250-300 nm. Neutral or slightly positive zeta
      potentials were measured for charge ratios of 3.5:1 and greater. DBP-PEG/DNA
      complexes, made with plasmids encoding the green fluorescent protein (GFP) and
      beta-Galactosidase (beta-Gal) genes, were used to transfect Chinese hamster ovary
      (CHO) cells. DBP-PEG/DNA was capable of transfecting cells and maximum
      transfection efficiency was observed for N:P ratios from 4:1 to 5:1,
      corresponding to zeta potentials from -4 to +1.6 mV. The effect of the DBP-PEG
      vehicle on cell viability was assayed. DBP-PEG was associated with a higher
      percentage of viable cells ( approximately 95%) than either polyethylenimine
      (PEI) or poly-L-lysine (PLL), and with transfection efficiency greater than PLL,
      but with somewhat lower than PEI. The results of this work demonstrate that PEG
      can be used as the backbone for gene delivery vehicles.

PMID- 17039466
TI  - Variation and causal factors of craniofacial robusticity in Patagonian hunter
      gatherers from the late Holocene.
AB  - Fueguian-Patagonian skulls have been characterized as some of the most robust of
      any modern crania. However, the causal factors of such robusticity remain
      unsettled. We assess within- and among-sample cranial robusticity of seven
      samples from continental Patagonia and Tierra del Fuego, using geometric
      morphometric techniques. In addition, the biomechanical, phylogenetic, and
      climatic hypotheses proposed to account for robusticity in such samples are
      discussed. Two Amerindian samples of farmers and two early middle Holocene
      samples from South America were included. The results show: 1) large variation in
      craniofacial robusticity among Patagonian samples, with the highest robusticity
      in samples from south continental Patagonia and Isla Grande of Tierra del Fuego,
      whereas central and north Patagonian samples display the same degree of
      robusticity as farmer samples; 2) that early middle Holocene samples display
      lower levels of robusticity than South Patagonian samples; and 3) strong
      association between latitude and craniofacial robusticity, with the most robust
      craniofacial morphologies occurring at the highest latitudes. In consequence,
      neither masticatory stress nor retention of ancestral features is supported by
      the morphological evidence analyzed. Hence it is hypothesized that endocrine
      changes related to cold climate may be a plausible explanation for several
      craniofacial features found in Fueguian and south continental Patagonian samples,
      such as their large masticatory component, and pronounced supraorbital ridge and
      glabellar region.

PMID- 17039467
TI  - Male lifespan and the secondary sex ratio.
AB  - Literature speculating on the fetal origins of later life morbidity often invokes
      the "damaged cohort" theory, i.e., that maternal responses to exogenous shocks
      induce "stress reactivity" in fetuses and thereby shorten the lifespan of males
      in utero during stressful times. A rival, or "culled cohort," theory posits that
      exogenous shocks to gravid females induce spontaneous abortions of frail male
      fetuses, leaving relatively hardy survivors who enjoy, on average, lifespans
      longer than males in less stressed birth cohorts. A recent test based on archival
      data from Sweden supported the culled cohort theory. Several characteristics of
      the Swedish data, however, raise questions regarding the external validity of the
      findings. We repeat the test with data from Denmark, Iceland, and England and
      Wales. We use time-series methods that control for trends, seasonal cycles, and
      other forms of autocorrelation that could confound the test. None of the results
      supports the "damaged cohort" theory. Consistent with the Swedish findings and
      with evolutionary theory, we find support in Iceland and England and Wales for
      the "culled cohort" theory. We discuss the implications of our findings for basic
      research as well as for public health.

PMID- 17039468
TI  - Menstrual cycle irregularities are associated with testosterone levels in healthy
      premenopausal women.
AB  - High androgen levels have been associated with menstrual irregularities in
      clinical populations, but not in healthy women. We examined the association
      between testosterone and menstrual irregularities in a nonclinical population of
      194 healthy premenopausal women, none of whom reported chronic health conditions.
      Women provided saliva samples for assay of salivary testosterone, and responded
      to questions about length of menstrual cycles, variability in menses, and
      retrospective history of menstrual irregularity. Results showed significant
      correlations between testosterone and menstrual irregularities, even when women
      with the most irregular cycles were excluded from analyses. This pattern was also
      apparent for a subgroup of 27 women using hormonal contraceptives. Based on our
      findings, it appears that even in healthy women reporting no health concerns,
      menstrual irregularities are associated with higher levels of circulating
      androgens.

PMID- 17039469
TI  - A possible link between prenatal exposure to famine and breast cancer: a
      preliminary study.
AB  - In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to
      prenatal famine more often reported a history of breast cancer than nonexposed
      women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had
      alterations in reproductive risk factors. Prenatal famine may increase breast
      cancer incidence.

PMID- 17039470
TI  - Hair morphology and anthropological applications.
AB  - The histological study of hair has a long history, dating from the 19th century.
      We obtained a collection of hair taken from people of known geographic origin. We
      analyzed these samples according to their transversal cut shape index, derived
      from computerized image-processing. We noted statistically significant variation
      according to the geographic origin of subjects. This morphological variation may
      reflect genetic distance. This reliable, quick, and cheap technique could be used
      in other existing anthropological material for which DNA analysis is usually
      difficult.

PMID- 17039471
TI  - Sex hormone-binding globulin and androgen levels in immigrant and British-born
      premenopausal British Pakistani women: evidence of early life influences?
AB  - In women, raised insulin levels are associated with low sex hormone-binding
      globulin (SHBG) and high androgen levels, which are in turn linked to
      infertility. Since insulin resistance and hyperinsulinemia are major health
      problems for South Asians living in Western countries, we predicted that British
      Pakistani women would have low SHBG and raised androgen levels compared to
      European women. Given low birth weights in Pakistan, and known links between low
      birth weight and insulin resistance in later life, we also predicted that
      immigrant women born in Pakistan would have lower levels of SHBG and higher
      levels of androgens than British-born British Pakistani women. We assessed SHBG,
      testosterone, and the free androgen index (FAI) from a single serum sample taken
      on days 9-11 of the menstrual cycle from 20-40-year-old women living in the UK:
      30 immigrants from Pakistan, 30 British-born British Pakistani women, and 25
      British-born women of European origin. Age-adjusted analyses showed no
      significant differences in SHBG, testosterone, or FAI between British-born
      Pakistani and European-origin women. However, immigrant British Pakistani women
      had a significantly higher FAI than British-born British Pakistani women.
      Adjustment for body mass index, waist-to-hip ratio, and smoking status did not
      affect these results, but further adjustment for height, a marker of early
      environment, reduced the P-value for the difference in FAI between immigrant and
      British-born British Pakistani women to below significance. It is possible that
      the poorer early environment of immigrant British Pakistani women was at least
      partially responsible for their relatively high levels of free androgens.

PMID- 17039472
TI  - Secondary sex ratio variation during stressful times: the impact of the French
      revolutionary wars on a German parish (1787-1802).
AB  - The observation that declines in the human secondary sex ratio (SSR) may be
      linked to stressful periconceptional periods has received considerable attention
      (Catalano [2003] Hum Reprod 18:1972-1975; Catalano et al. [2005] Int J Epidemiol
      34:944-948, [2005] Hum Reprod 20:1221-1227, [2005] Paediatr Perinat Epidemiol
      19:413-420). For the purpose of testing the external validity of this phenomenon,
      birth records from four German village genealogies (N = 1,048) were analyzed to
      study the impact of the French Revolutionary Wars (1787-1802) on the proportion
      of male births. All births were subdivided into three cohorts (prewar, 1787-1792;
      war, 1792-1797; and postwar, 1797-1802). Differences in SSR between cohorts
      achieved statistical significance (chi2= 7.695; df = 2; P = 0.021). In addition,
      changes in SSR before, during, and after the wars were monitored by risk
      analysis. Using the SSR of the prewar period as a control, the results of the war
      cohort failed to achieve statistical significance (regression coefficient, 
      0.257; ExpB= 0.773; P = 0.118), while the odds reduction of 32.3% in the postwar
      period proved to be statistically significant (regression coefficient, -0.390;
      ExpB= 0.677; P = 0.006). It is hypothesized that the experience of postwar
      economic hardship (attributable to lowered food availability paired with dietary
      changes) represents the most likely proximate cause. The study also finds
      evidence of a parental sex ratio manipulation strategy meant to offset the female
      biased SSR after the wars. It is argued that from an evolutionary perspective
      both the decline in SSR in response to stress as well as parental manipulation of
      the tertiary sex ratio convey reproductive advantages.

PMID- 17039473
TI  - Measurement of leptin in dried blood spot samples.
AB  - Leptin is important in a wide range of physiological processes, but logistical
      constraints associated with venipuncture blood collection have limited research
      on leptin in diverse, community-based settings. The aim of this short report is
      to present and validate an enzyme immunoassay method for quantifying leptin in
      samples of capillary whole blood collected from a simple finger prick and dried
      on filter paper. The method was evaluated through analysis of precision,
      reliability, stability, and comparisons with matched plasma and blood spot
      samples. We report acceptable levels of assay precision and reliability, and good
      agreement between results obtained from matched plasma and blood spot samples (r
      = 0.976, P < 0.001). Leptin concentrations begin to deteriorate after only 3 days
      at room temperature. Thus, care should be taken to refrigerate or freeze samples
      promptly. The relative ease of blood spot sample collection may facilitate
      research on leptin in a wider range of cultural and ecological settings.

PMID- 17039474
TI  - High-sensitivity C-reactive protein, adiposity, and blood pressure in the Yakut
      of Siberia.
AB  - C-reactive protein (CRP), an acute-phase reactant and marker of inflammatory
      response, is known to be an important predictor of future cardiovascular
      mortality, independent of other risk factors. The purpose of this research was to
      investigate the association between CRP, adiposity, and blood pressure in the
      Yakut, an indigenous Siberian population undergoing rapid cultural change. We
      conducted a cross-sectional study of 265 healthy Yakut adults in six villages in
      rural northeastern Siberia. Plasma CRP was measured by high-sensitivity
      immunoturbidimetric assay. The median CRP value was 0.85 mg/l, with values for
      the 25th, 50th, and 75th percentiles of 0.30, 0.85, and 2.28 mg/l, respectively.
      CRP was positively associated with age (r = 0.19; P = 0.002), but not plasma
      lipids or smoking status. CRP was associated with measures of central adiposity
      and characteristics of the metabolic syndrome, particularly in women. We found
      significantly higher CRP across quintiles (Q) of waist circumference for women
      (difference = 0.7 mg/l; P = 0.035), but not men (difference = 0.36 mg/l; P =
      0.515). CRP was significantly associated with systolic blood pressure in men
      (difference, Q1 vs. Q5 = 1.1 mg/l; P = 0.044) but not women (difference, Q1 vs.
      Q5 = 0.03 mg/l; P = 0.713) after adjusting for age, waist circumference, and
      smoking status. CRP in the Yakut was considerably lower than was reported for
      other populations. The low CRP levels may be explained in part by a low
      prevalence of abdominal obesity. Among the Yakut, the high physical-activity
      demands of a traditional herding lifeway likely play a role through high energy
      expenditure and maintenance of negative energy balance. Our findings underscore
      the need for further research on the metabolic activity of adipose tissue, blood
      pressure, and inflammatory activation in non-Western populations.

PMID- 17039475
TI  - Digit ratio and hand-grip strength in German and Mizos men: cross-cultural
      evidence for an organizing effect of prenatal testosterone on strength.
AB  - The ratio of the length of the second and fourth digits (2D:4D), a putative proxy
      of prenatal testosterone (PT), is correlated with measures of physical fitness.
      The relationship between the organizing effect of PT on physical fitness is
      likely to arise as a response to intrasexual male competition for females.
      Physical strength is also likely to be important in intrasexual conflict, but
      nothing is known concerning the relationship between 2D:4D and strength. The
      strength of an individual is strongly influenced by body size, and 2D:4D is
      strongly dependent on ethnicity. We present evidence that strength, as measured
      from hand-grip strength, is related to 2D:4D in samples from two ethnic groups
      (52 Caucasian men from Germany, and 88 Oriental Mizos men from northeast India)
      which differed markedly in size. We found that 1) the German men were heavier and
      stronger, but had higher 2D:4D (lower PT) than the Mizos men; 2) a median split
      for grip strength into low (LGS) and high (HGS) groups showed that for right-hand
      2D:4D (but not left-hand 2D:4D), the LGS men had higher 2D:4D than the HGS men;
      and 3) the relationships between right 2D:4D and grip strength were independent
      of ethnicity, age, height, and weight. Measures of grip strength correlate
      strongly with strength in other muscle groups, so we conclude that PT may have an
      early organizing effect on strength in men, and this is likely to be widespread
      in human groups.

PMID- 17039476
TI  - Use of serial ultrasound to identify periods of fetal growth restriction in
      relation to neonatal anthropometry.
AB  - The developmental origins of the health and disease hypothesis suggests that
      fetal growth restriction (FGR) is a risk factor for several chronic diseases of
      adulthood. However, most supporting studies use birth weight as a proxy measure
      of FGR. To examine the relationship between birth weight and FGR, the present
      study used serial prenatal ultrasound to identify periods of FGR during
      gestation, and related these periods to birth size and shape. The data in this
      study included serial prenatal ultrasounds performed on 1,349 high-risk
      Scandinavian women enrolled in the National Institute of Child Health and Human
      Development Study of Successive Small for Gestational Age Births. Fetal growth
      velocity between ultrasounds was used to identify periods of isolated FGR, and
      these were studied in relation to anthropometry at birth. FGR was identified in
      184 subjects. A control group of 384 subjects without FGR was also identified.
      Infants with first-trimester FGR (n = 20) had the highest birth weight, ponderal
      index, and subscapular skinfold thickness. Infants with second-trimester FGR (n =
      37) had the highest arm fat percentage. Infants with early third-trimester FGR (n
      = 55) had the lowest mean birth weight and ponderal index. When infant gender,
      gestational age, maternal body mass index, and smoking were controlled, birth
      weight was predicted only by third-trimester FGR (not first- or second-trimester
      FGR), and arm fat percent was predicted only by second-trimester FGR. These
      results suggest that birth weight is not a valid indicator of FGR occurring
      before the third trimester. Body composition may be a more sensitive marker of
      early FGR.

PMID- 17039477
TI  - Inbreeding from isonymy and repeated pairs of surnames in the Ebro Delta region
      (Tarragona, Spain).
AB  - The aim of the study was to evaluate the levels of inbreeding calculated from
      isonymy with its random (Fr) and nonrandom (Fn) components, and repeated pairs of
      surnames (RP2) and their random component (RP2r) in the Ebro River Delta region
      (Tarragona, Spain). This region is made up of four parishes, and data correspond
      to the period 1939-1995. The global results are on the same levels as observed in
      other studies, but the values obtained in 3 of 4 parishes are relatively high.
      The Fn global value is higher than Fr, as opposed to what happens in each parish,
      so there is a clear Wahlund effect of subdivision of the region into parishes.
      Among the parishes there is a clear differentiation for Amposta, with values much
      lower than for the rest, due to the behavior of this population, i.e., a high
      immigration rate.

PMID- 17039478
TI  - Incorporating psychosocial health into biocultural models: preliminary findings
      from Turkana women of Kenya.
AB  - This paper investigates the potential benefits and limitations of including
      psychosocial stress data in a biocultural framework of human adaptability.
      Building on arguments within human biology on the importance of political
      economic perspectives for examining patterns of biological variation, this paper
      suggests that psychosocial perspectives may further refine our understanding of
      the mechanisms through which social distress yields differences in health and
      well-being. To assess a model that integrates psychosocial experiences, we
      conducted a preliminary study among nomadic pastoralist women from northern
      Kenya. We interviewed 45 women about current and past stressful experiences, and
      collected anthropometric data and salivary cortisol measures. Focus group and key
      informant interviews were conducted to refine our understanding of how the
      Turkana discuss and experience distress. The results suggest that the most
      sensitive indicators of Turkana women's psychosocial experiences were the
      culturally defined idioms of distress, which showed high concordance with
      measures of first-day salivary cortisol. Other differences in stress reactivity
      were associated with the frequent movement of encampments, major herd losses, and
      direct experiences of livestock raiding. Despite the preliminary nature of these
      data, we believe that the results offer important lessons and insights into the
      longer-term process of incorporating psychosocial models into human adaptability
      studies.

PMID- 17039479
TI  - Serum cobalt in children with essential hypertension.
AB  - The effect of cobalt on the cardiovascular system is one of many aspects of
      cobalt metabolism in humans. Elastin and collagen are the main proteins of the
      vascular wall. The aims of this study were: 1) to determine serum cobalt
      concentrations in children with hypertension; and 2) to study the correlation
      between serum cobalt and some biological markers of the extracellular matrix of
      the vascular wall, i.e., anti-elastin and anti-collagen type IV antibodies.
      Patients showed statistically significant higher levels of systolic and diastolic
      blood pressure, and significantly lower serum cobalt concentrations, than
      controls. Children with hypertension showed significantly higher levels of total
      cholesterol (P = 0.0003) and collagen type IV IgM (P = 0.04). Collagen type IV
      IgG levels (P = 0.027) were lower than in controls. Serum cobalt in patients
      showed a correlation with systolic blood pressure (r = -0.44, P = 0.05), elastin
      IgM (r = 0.60, P = 0.007), and collagen type IV IgG (r = -0.46, P = 0.04). Our
      data suggest the existence of a correlation between changes in levels of serum
      cobalt, total cholesterol, anti-collagen type IV antibodies, and essential
      hypertension in children. This is the first study of serum cobalt in children
      with essential hypertension.

PMID- 17039480
TI  - Prevalence of dopamine and 5HT2C receptor polymorphisms in Amerindians and in an
      urban population from Argentina.
AB  - We report on the frequency of DRD2A1, DRD3A1, DRD4/2R-10R, and 5HT2CA1 variants
      in the population of the city of La Plata (Argentina) and in Amerindians from
      Argentina, Paraguay, and Chile. In the Amerindian sample, the prevalence of
      DRD2A1 and DRD4/4R variants were, respectively, significantly lower and
      significantly higher than frequencies reported in other Native Americans.
      Comparison of average allele and genotype frequencies between La Plata and
      Amerindians showed significant differences for 5HT2CA1 and DRD4. As La Plata is a
      population with predominant European and Amerindian components, we used mtDNA and
      Y-specific markers to subdivide the La Plata sample into two strata: Amerindian
      La Plata and non-Amerindian La Plata. Significant variations between the two
      strata were detected for DRD2A1, DRD3A1, and DRD4/4R allele frequencies, and for
      the homozygous DRD4/4R/4R genotype. Several controversial reports suggest a
      possible association between a variant of DRD and/or 5HT2C receptor genes and the
      clinical expression of several psychiatric disorders. We suggest that ethnic
      variations in the prevalence of the allelic forms of these genes may be a
      confounding factor to be taken into consideration in studies of association
      between dopaminergic and serotonergic receptor genotypes and neuropsychiatric and
      mood disorders.

PMID- 17039481
TI  - Y-chromosome genetic variation in Rio de Janeiro population.
AB  - The present-day Brazilian gene pool is known to be the outcome of an admixture
      process of populations from different origins, mainly Amerindians, Europeans, and
      Africans. It is also known that in Brazil, a wide variation in the admixture
      process occurred in different regions of the country or even in different
      subpopulations from the same region. In the present study, we aimed to
      characterize the male lineages present in the Rio de Janeiro population, the
      second most populated of the 26 Brazilian states. A random sample of 127
      unrelated males from Rio de Janeiro was typed for 28 Y-chromosome-specific
      biallelic markers. In total, 17 different haplogroups were defined within our
      sample, most of them of European ancestry (88.1%). Those of sub-Saharan African
      origin (E3a) amounted to 7.9%, while only 2 males carried Amerindian lineages
      (characterized by the presence of an M3 mutation: haplogroup Q3). Using both Y
      STR haplotype and Y-SNP haplogroup information, genetic distances were calculated
      between the subgroup of Rio de Janeiro males carrying European haplogroups and
      the Portuguese population. Low, nonsignificant, values were obtained. Thus, in
      contrast with what is observed in their female counterparts, the vast majority of
      the present Rio de Janeiro male gene pool is of European extraction, while the
      original Amerindian lineages are residual and much less frequent than the sub
      Saharan component resulting from the slave trade. These observations can be
      interpreted as the signature of the strong gender asymmetry of the admixture
      processes in colonial systems.

PMID- 17039482
TI  - Height and weight of primary schoolchildren in Shiraz city, southern Iran, 2002.
AB  - This paper aims at presenting updated growth reference data for height and weight
      of 2,397 healthy schoolchildren (1,268 boys and 1,129 girls) aged 6.5-11.5 years
      in Shiraz (Iran), using a multistage sampling scheme. Our schoolchildren are now
      significantly taller and heavier for their age than their peers born 15 years
      earlier. However, the statistical models for estimating age-related centiles were
      consistent. A comparison of our current data with Centers for Disease Control
      growth charts for 2000 show that our height and weight medians correspond almost
      to the 40th centile of the latter, indicating less of a deficit than the previous
      growth study in Shiraz. We conclude that it is more realistic to use local growth
      standards for clinical work in Iran, which should be updated periodically.

PMID- 17039483
TI  - Human skeletal muscle size and architecture: variability and interdependence.
AB  - Seven hundred and eleven women and men (aged 3-94 years, including normal
      individuals and highly trained bodybuilders) were tested for the thickness and
      pennation angles of their triceps brachii (TB), vastus lateralis (VL), and
      gastrocnemius medialis (GM) muscles. The variations of muscle thickness and
      pennation angles were largest in TB (6-66 mm and 5-55 degrees), followed by VL (8
      45 mm and 7-33 degrees) and GM (11-36 mm and 12-33 degrees), and women showed
      smaller variations than men. These results suggest the existence of muscle- and
      gender-specificity in the variability of muscle dimensions. Significant positive
      correlations were observed between muscle thickness and pennation angles (r =
      0.81, 0.61, and 0.56, for TB, VL, and GM, respectively), indicating that the size
      dependence of the pennation angle is a general feature of pennate muscles.

PMID- 17039484
TI  - Identification of the human/mouse syntenic common fragile site FRA7K/Fra12C1-
      relation of FRA7K and other human common fragile sites on chromosome 7 to
      evolutionary breakpoints.
AB  - Common fragile sites (CFSs) are expressed as chromosome gaps in cells of
      different species including human and mouse as a result of the inhibition of DNA
      replication. They may serve as hot spots for DNA breakage in processes such as
      tumorigenesis and chromosome evolution. Using multicolor fluorescence in situ
      hybridization mapping, the authors describe here human CFS FRA7K on chromosome
      band 7q31.1 and its murine homolog Fra12C1. Within the syntenic FRA7K/Fra12C1
      region lies the IMMP2L/Immp2l gene with a size of 899/983 kb. The authors further
      mapped 2 amplification breakpoints of the breast cancer cell line SKBR3 to the
      CFSs FRA7G and FRA7H. The 5 molecularly defined CFSs on chromosome 7 do not
      preferentially colocalize with synteny breaks between the human and mouse genomes
      and with intragenomic duplications that have occurred during chromosome
      evolution. In addition, in contrast to all currently reported data, CFSs in
      chromosome band 7q31 do not show increased DNA helix flexibility in comparison
      with control regions without CFS expression.

PMID- 17039485
TI  - Difference in time course of modulation of synaptic transmission by group II
      versus group III metabotropic glutamate receptors in region CA1 of the
      hippocampus.
AB  - We investigated the time course of modulation of synaptic transmission by group
      II and group III metabotropic glutamate receptors in region CA1 of the
      hippocampus. In the presence of 50 microM picrotoxin, pressure pulse application
      of 1 mM glutamate resulted in a fast onset of suppression of synaptic
      transmission in stratum lacunosum moleculare and a slower onset of suppression in
      stratum radiatum, with both effects returning to baseline over the course of
      several minutes. Application of 50 microM of the group II agonist (2R,4R)-APDC in
      stratum lacunosum moleculare resulted in the same fast onset of suppression while
      having no effect in stratum radiatum. Pressure pulse application of 100 microM DL
      AP4 in stratum lacunosum moleculare and stratum radiatum resulted in a much
      slower onset of suppression of synaptic transmission than (2R,4R)-APDC.
      Suppression by (2R,4R)-APDC was accompanied by a rapid enhancement of paired
      pulse facilitation, indicative of a presynaptic mechanism. This demonstrates that
      activation of group II mGluRs in the hippocampus causes a fast onset of
      suppression in stratum lacunosum moleculare, while activation of group III mGluRs
      causes a slower onset of suppression. The difference in time course for group II
      vs. group III mGluRs suggests a different functional role, with group II playing
      a potential role in making synapses act as low pass filters.

PMID- 17039486
TI  - Bidirectional redistribution of AMPA but not NMDA receptors after perforant path
      simulation in the adult rat hippocampus in vivo.
AB  - Long-term potentiation (LTP) in vitro reveals dynamic regulation of synaptic
      glutamate receptors. AMPA receptors may be inserted into synapses to increase
      neurotransmission, whereas NMDA receptors may redistribute within the synapse to
      alter the probability of subsequent plasticity. To date, the only evidence for
      these receptor dynamics in the hippocampus is from the studies of dissociated
      neurons and hippocampal slices taken from young animals. Although synaptic
      plasticity is induced easily, the extent of AMPA and NMDA receptor mobility after
      LTP is unknown in the adult, intact hippocampus. To test whether AMPA or NMDAR
      subunits undergo activity-dependent modifications in adult hippocampal synapses,
      we induced LTP at perforant path-dentate gyrus (DG) synapses in anesthetized
      adult rats, using high frequency stimulation (HFS), verified layer-specific Arc
      induction, and analyzed the distribution of postsynaptic AMPA and NMDAR subunits,
      using immunogold electron microscopy. The number of synapses with AMPA receptor
      labeling increased with LTP-inducing HFS in the stimulated region of the dendrite
      relative to the nonstimulated regions. The opposite trend was noted with low
      frequency stimulation (LFS). Moreover, HFS increased and LFS decreased the ratio
      of synaptic to extrasynaptic AMPA receptor labeling in the postsynaptic membrane.
      In contrast, HFS did not significantly alter NMDAR labeling. Thus, LTP in the
      adult hippocampus in vivo selectively enhanced AMPA but not NMDAR labeling
      specifically in synapses undergoing activity-dependent plasticity relative to the
      remainder of the dendritic tree. The results suggest a mechanism by which rapid
      adjustments in synaptic strength can occur through localized AMPA receptor
      mobility and that this process may be competitive across the dendritic tree.

PMID- 17039487
TI  - Hippocampal contributions to recollection in retrograde and anterograde amnesia.
AB  - Lesions restricted to the hippocampal formation and/or extended hippocampal
      system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic
      nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving
      familiarity-based memory relatively intact. Familiarity may be supported by extra
      hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in
      recognition memory best exemplify this distinction in anterograde amnesia. The
      authors report for the first time comparable dissociations within recognition
      memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and
      septal nuclei lesions failed to recognize details pertaining to personal past
      events only when recollection was required, during recognition of episodic
      details. His intact recognition of generic and semantic details pertaining to the
      same events was ascribed to intact familiarity processes. Recollective processes
      in the controls were reflected by asymmetrical Receiver's Operating
      Characteristic curves, whereas the patient's Receiver's Operating Characteristic
      was symmetrical, suggesting that his inferior recognition performance on episodic
      details was reliant on familiarity processes. Anterograde and retrograde memories
      were equally affected, with no temporal gradient for retrograde memories. By
      comparison, another amnesic person (K.C.) with extensive MTL damage (involving
      extra-hippocampal MTL structures in addition to hippocampal and fornix lesions)
      had very poor recognition and no recollection of either episodic or
      generic/semantic details. These data suggest that the extended hippocampal system
      is required to support recollection for both anterograde and retrograde memories,
      regardless of their age.

PMID- 17039488
TI  - Incidence of bacteremias and invasive mycoses in children with high risk
      neuroblastoma.
AB  - BACKGROUND: Information on the incidence of infectious complications during for
      treatment for high risk neuroblastoma (HR-NB) is limited. Bacteremias and
      invasive mycoses may be considered surrogate markers of the infection burden.
      PATIENTS AND METHODS: Data on bacteremias and invasive mycoses occurring during 3
      consecutive protocols for front line (NB-89; NB-92; NB-97) or salvage therapy
      (TVD) for HR-NB were reviewed. The cumulative risk of developing a first episode
      and the rate of infections during the entire length of each protocol were
      evaluated. RESULTS: Front line protocols were given to 80 patients for a total of
      22,070 days at risk; salvage treatment was given to 24 children for 2,909 days at
      risk. During front line therapy 41 infectious episodes were diagnosed in 29 (36%)
      patients, for a 45% cumulative risk and an infection rate (IR) of 0.19/100
      patient-days-at risk. Salvage therapy determined five infectious episodes in four
      (17%) patients, with a 39% cumulative risk, and an IR of 0.17. The IR during the
      phase of high dose chemotherapy with hematopoietic stem cell rescue (megatherapy)
      included in the three front line protocols decreased over time (1.54 in NB-89;
      0.52 in NB-92 and 0.0 in NB 97; P = 0.001), possibly because of the use of less
      aggressive conditioning regimens, without radiotherapy. CONCLUSIONS: The IRs of
      protocols for HR-NB did not change over time. The megatherapy-related phases are
      those at highest risk.

PMID- 17039489
TI  - Respiratory symptoms in a boy revealing Carney triad.
AB  - The association of gastrointestinal stromal cell tumor (GIST), paraganglioma, and
      pulmonary chondroma is known as the Carney triad, occurring predominantly in
      young adult females. We present the case of a 14-year-old male with respiratory
      symptoms resulting in the diagnosis Carney triad.

PMID- 17039490
TI  - Diffusion of nutrients molecules and model drug carriers through mucin layer
      investigated by magnetic resonance imaging with chemical shift resolution.
AB  - Magnetic resonance imaging (MRI) with chemical shift resolution is a recent
      extension of MRI and it provides information about species resolved molecular
      transport on the macroscopic scale in complex systems. In this contribution, we
      show that by using this novel method, one can predict the behavior of drug and
      food molecules when they are in contact with the mucosal layer in the
      gastrointestinal tract. For the first time, the transport properties of a mixture
      of nutrients (i.e., a solution of ethanol and glucose) and of a model drug
      carrier (i.e., an equimolar solution of cationic and nonionic surfactants)
      through a mucin gel have been investigated. This study shows that transport
      properties of the diffusing molecules through a mucin gel are dependent on their
      size and physicochemical properties. In addition, we show that mucin gel acts as
      an efficient selective barrier. It favors the disintegration of mixed micelles of
      nonionic and cationic surfactants by stopping the diffusion of cationic
      surfactants with slightly affecting the diffusion of the nonionic surfactants.

PMID- 17039491
TI  - Nodal downstaging predicts survival following induction chemotherapy for stage
      IIIA (N2) non-small cell lung cancer in CALGB protocol #8935.
AB  - BACKGROUND AND OBJECTIVES: CALGB 8935 was a phase II protocol for
      mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction
      cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant
      cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of
      pathologic nodes. METHODS: Failure-free survival was calculated from a landmark 3
      months after resection to account for heterogeneity in adjuvant therapy. RESULTS:
      Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9
      had a median failure-free interval of 47.8 months from landmark, whereas the 33
      patients (79%) with persistent N2 disease had a median failure-free survival of
      8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete
      resection (positive highest resected node and/or margin), completeness of
      resection did not influence failure-free survival. There were 3 distant and no
      local recurrences among the N2 negative group, and 12 local recurrences among
      patients with residual N2 disease (P=0.041). CONCLUSIONS: These data suggest: (1)
      persistent N2 disease following induction chemotherapy is unfavorable; (2)
      patients downstaged to N2 negative may benefit from surgical resection; however,
      (3) 33% of N2 negative patients suffered disease relapse.

PMID- 17039492
TI  - Consideration of serum glucose levels during malignant mediastinal lymph node
      detection in non-small-cell lung cancer by FDG-PET.
AB  - BACKGROUND AND OBJECTIVE: Glucose and FDG compete for uptake by cancers. Here, we
      undertook to improve diagnostic accuracy of FDG-PET for determining mediastinal
      lymph node (LN) status in NSCLC by considering serum glucose level. METHODS:
      NSCLC patients (n = 70) who underwent curative lung resection and mediastinal LN
      dissection within 1 month of FDG-PET were enrolled. MaxSUV was calculated using
      lean body weight and used to determine a new parameter (maxSUV x serum glucose
      level; maxSUV-GL). Histopathologic LN results were compared with maxSUV and
      maxSUV-GL values. RESULTS: Of 71 LN stations whose FDG uptake could be measured,
      21 were malignant and 50 benign. MaxSUV of LN had AUC of 0.729 (95% CI: 0.610
      0.827) by ROC analysis with sensitivity of 47.6% (10/21), specificity of 94.0%
      (47/50), and a cutoff value of 3.3. Using maxSUV-GL the corresponding values
      were; AUC 0.825 (95% CI: 0.716-0.905) and sensitivity 76.2% (16/21), with a
      cutoff value of 290.4, which represented a significant improvement (P < 0.01)
      without compromising specificity 88.0% (44/50) (P > 0.05). The exclusion of neo
      adjuvant chemotherapeutic and diabetic patients resulted in a similar improvement
      in diagnostic accuracy. CONCLUSION: By considering serum glucose level during FDG
      PET using the new parameter maxSUV-GL, sensitivity for malignant mediastinal LN
      detection is improved.

PMID- 17039493
TI  - Theoretical study of interactions between muscle aldolase and F-actin: insight
      into different species.
AB  - Interactions of the glycolytic enzyme, fructose-1,6-bisphosphate aldolase
      (aldolase), with F-actin may be one mechanism for the colocalization of
      glycolytic enzymes. Examination of these interactions in different animal species
      tests this hypothesis by observing whether binding sites are conserved across
      species. Brownian dynamics (BD) simulations provide descriptions of such protein
      protein interactions with the muscle isoforms of zebra fish and human aldolase.
      The results are compared with previous results obtained for rabbit muscle and
      yeast. The aldolase binding groove previously determined in rabbit muscle is
      conserved in both the human and fish muscle isoforms. The nonspecific radial free
      energies of interaction are similar with fish being slightly weaker than human
      and rabbit: human, -2.27 +/- 0.05 kcal/mol; rabbit, -2.0 +/- 0.04 kcal/mol; and
      fish, -1.5 +/- 0.03 kcal/mol. BD results show a large Boltzmann population of
      complexes formed around the A/D and B/C grooves of aldolase with the most
      feasible binding mode comprising two aldolase subunits to subdomain I region of
      the actin subunits. These results show that the location of the important
      residues and binding site for fish and human aldolase is very similar to that in
      rabbit and that in different animals the binding site is conserved. This suggests
      that the binding interaction between aldolase and F-actin is general in animal
      muscles and is rendered possible and energetically favorable through the
      conservation of this binding site.

PMID- 17039494
TI  - Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.
AB  - Literature data relevant to the decision to allow a waiver of in vivo
      bioequivalence (BE) testing for the approval of immediate release (IR) solid oral
      dosage forms containing prednisolone are reviewed. Data on its solubility, oral
      absorption, and permeability are not totally conclusive, but strongly suggest a
      BCS Class 1 classification. Prednisolone's therapeutic indications and
      therapeutic index, pharmacokinetics, and the possibility of excipient
      interactions were also taken into consideration. Available evidence indicates
      that a biowaiver for IR solid oral dosage forms formulated with the excipients
      tabulated in this article would be unlikely to expose patients to undue risks.

PMID- 17039495
TI  - Densin is a novel cell membrane protein of Sertoli cells in the testis.
AB  - Cell-cell interactions between Sertoli cells and germ cells are crucial for the
      maturation of germ cells in spermatogenesis but the structural and functional
      aspects of the interactions remain to be fully elucidated. Densin is a junction
      protein suggested to play a role in establishment of specific cell-cell contacts
      in the post-synaptic densities of the brain and the slit diaphragm of the kidney
      podocyte. In the present study, densin was discovered to be expressed in the
      testis of the man and the mouse. Expression of densin at the gene and the protein
      level was studied by using RT-PCR and Western blotting analyses, and the
      localization of densin was explored with immunofluorescence staining. RT-PCR and
      Western blotting analyses showed that densin is expressed at the gene and the
      protein levels. Immunofluorescence staining localized the expression of densin to
      the cell membranes of Sertoli cells suggesting that densin may be an adherens
      junction protein between Sertoli cells and developing germ cells. Densin is a
      novel testicular protein expressed in the cell membranes of Sertoli cells. Its
      functional role remains to be assessed.

PMID- 17039496
TI  - The risk of secondary malignancies over 30 years after the treatment of non
      Hodgkin lymphoma.

PMID- 17039498
TI  - Cancer-specific mortality after radiation therapy with short-course hormonal
      therapy or radical prostatectomy in men with localized, intermediate-risk to high
      risk prostate cancer.
AB  - BACKGROUND: The presence of multiple determinants of aggressive cancer biology
      may impact prostate cancer-specific mortality (PCSM) rates compared with fewer
      factors. The authors estimated PCSM after radiation therapy with short-course
      androgen suppression therapy (RT+AST) or radical prostatectomy (RP) in men with
      clinically localized, intermediate-risk to high-risk prostate cancer. METHODS:
      The study cohort included 3240 men treated from 1981 to 2002 with RT with 6
      months of AST (n = 550) or RP (n = 2690) for localized prostate cancer with at
      least 1 risk factor (prostate-specific antigen [PSA] >10 ng/mL, biopsy Gleason
      score 7-10, or clinical tumor category T2b or T2c). Competing risks regression
      analyses were used to determine whether the number of risk factors present was
      associated with time to PCSM. RESULTS: Men with all 3 risk factors had
      significantly shorter time to PCSM after RT+AST (adjusted hazards ratio [HR] of
      9.3; 95% confidence interval [95% CI], 1.9-44.5 [P(Gray) = .005]) or RP (adjusted
      HR of 6.3; 95% CI, 3.2-12.2 [P(Gray) < .001]) when compared with men with any 1
      or 2 risk factors. The 7-year estimates of PCSM for men having 1, 2, or 3 risk
      factors were 0.83% (95% CI, 0.27-1.4%), 2.6% (95% CI, 1.0-4.2%), and 12.6% (95%
      CI, 7.1-18.1%), respectively. CONCLUSIONS: Men with multiple determinants of
      intermediate-risk to high-risk prostate cancer have significantly increased
      estimates of PCSM despite aggressive therapy compared with men with only 1 or 2
      determinants. These men are appropriate candidates for enrollment onto randomized
      controlled trials evaluating the benefit of adding systemic therapies such as
      docetaxel to RT+AST or RP.

PMID- 17039499
TI  - Quality measures for the use of adjuvant chemotherapy and radiation therapy in
      patients with colorectal cancer: a systematic review.
AB  - BACKGROUND: Chemotherapy (CT) and radiation therapy (RT) are essential components
      of adjuvant (preoperative or postoperative) therapy for many patients with
      colorectal cancer (CRC); however, quality measures (QMs) of these critical
      aspects of CRC treatment have not been characterized well. Therefore, the authors
      conducted a systematic review of the literature to determine the available QMs
      for adjuvant CT and RT in patients with CRC and rated their usefulness for
      assessing the delivery of quality care. METHODS: The MEDLINE and Cochrane data
      bases were searched for all publications that contained potential/actual QMs
      pertaining to adjuvant therapy for CRC. Identified QMs were rated by using
      criteria developed by the National Quality Forum. RESULTS: Thirty-two articles
      met the established inclusion/exclusion criteria. Those 32 articles contained 12
      potential or actual QMs, 6 of which had major flaws that limited their
      applicability. The most useful QMs identified were 1) the percentage of patients
      with AJCC Stage III colon cancer who received postoperative CT and 2) the
      percentage of patients with Stage II or III rectal cancer who received
      chemoradiotherapy. CONCLUSIONS: To the authors' knowledge, very few QMs
      pertaining to adjuvant CT or RT for CRC have been published to date, and only
      half of those measures were rated as useful, acceptable, and valid in the current
      literature review. Future research should focus on refining existing QMs and on
      developing new QMs that target important leverage points with respect to the
      provision of adjuvant therapy for patients with CRC.

PMID- 17039500
TI  - Neoplastic stem cells: a novel therapeutic target in clinical oncology.
AB  - Cancer is among the leading causes of morbidity and mortality in the Western
      world. Despite recent advances, most therapeutic approaches fail to eradicate the
      entire neoplastic clone. The remaining cells often develop metastasis and/or
      recurrences and therefore may represent attractive targets of therapy. A new
      exciting concept in this regard suggests that each neoplasm represents a
      heterogeneous population of cells that pertain to long-term tumor growth both in
      vivo in the natural host and in experimental animals. This concept postulates the
      existence of small fractions of 'tumor stem cells' that exhibit a capacity for
      self-renewal and unlimited growth and therefore are distinct from their progeny.
      Based on these hypotheses, the targeting of neoplastic stem cells is considered
      indispensable for eradication of the entire clone and for the development of
      curative treatment approaches. However, tumor stem cells often may be quiescent
      cells and may express a different profile of targets compared with 'more mature'
      tumor cells. Therefore, current efforts have attempted to characterize target
      expression profiles in cancer stem cells in various malignancies. In the this
      review, the authors have provided a brief summary of the current knowledge of
      neoplastic stem cells and the application of respective concepts in translational
      oncology with the ultimate objective of improving anticancer therapy.

PMID- 17039501
TI  - Is intraoperative touch imprint cytology of sentinel lymph nodes in patients with
      breast cancer cost effective?
AB  - BACKGROUND: Sentinel lymph nodes (SLNs) are generally evaluated postoperatively,
      requiring 5-7 days for assessment. SLNs can also be evaluated intraoperatively by
      using touch imprint cytology (TIC), thus providing the surgeon immediate feedback
      and allowing for concurrent completion node dissection (CND) for positive SLNs.
      The authors hypothesized that TIC, when compared with standard postoperative SLN
      assessment alone, would permit a cost-effective evaluation of SLNs in patients
      with clinically node-negative breast cancer. METHODS: A decision-analysis model
      was created to compare TIC with standard postoperative SLN assessment alone.
      Sensitivity and specificity of TIC were determined prospectively from 342
      patients who underwent SLN biopsy assessed by both techniques. Short-term health
      states associated with surgical staging were defined, and utilities were
      estimated using EuroQol-5D. Base-case analysis was performed to estimate quality
      adjusted life years and the incremental cost-effectiveness ratio. Sensitivity
      analyses were performed to examine stability of model parameters. RESULTS: For
      each tumor stage, TIC was cost effective, and for patients with larger tumors (T3
      and T4), TIC was the dominant strategy. The analysis was robust to changes in
      sensitivity and specificity of TIC, prevalence of metastasis, probability of
      complications, and cost. However, when utility associated with standard SLN
      assessment was 0.9 or greater, this became the preferred strategy. CONCLUSIONS:
      TIC is cost effective for assessing SLN metastasis intraoperatively. For patients
      with larger tumors, it is not only more effective, but also less costly than
      standard SLN assessment alone. TIC may be particularly useful for patients who
      experience significant anxiety while awaiting results of standard SLN assessment.

PMID- 17039502
TI  - Molecularly targeted therapy for melanoma: current reality and future options.
AB  - Effective therapy for melanoma remains an unmet goal, with most traditional
      therapies representing inadequate trade-offs among the several goals of
      specificity, efficacy, and toxicity. Targeted molecular therapeutics are tailored
      to genetic abnormalities that are associated with tumor progression. Modulation
      of aberrant signaling pathways in cancer cells has the potential to provide more
      effective and potentially nontoxic therapy for a broad range of cancers,
      including melanoma. Among the possible targets in melanoma are the Ras-MAPK and
      PI3K/AKT signal transduction pathways, the proteasome, histone deacetylases,
      methyltransferases, and melanoma-induced angiogenesis.

PMID- 17039505
TI  - Randomized trial versus registry data--comparing apples and ORCHIDs.

PMID- 17039503
TI  - Multiinstitutional validation of the UCSF cancer of the prostate risk assessment
      for prediction of recurrence after radical prostatectomy.
AB  - BACKGROUND: The University of California, San Francisco (UCSF) Cancer of the
      Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the
      risk of biochemical recurrence after radical prostatectomy. The performance of
      the index is at least as good as the best available instruments based on clinical
      variables, and the 0 to 10 score is simple to calculate for both clinical and
      research purposes. This study used a large external dataset to validate CAPRA.
      METHODS: Data were abstracted from the Shared Equal Access Regional Cancer
      Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy
      at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the
      database, 1346 (64%) had full data available to calculate the CAPRA score.
      Performance of the CAPRA score was assessed with proportional hazards regression,
      survival analysis, and the concordance (c) index. RESULTS: Of the studied
      patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six
      percent suffered recurrence; median follow-up among patients who did not recur
      was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39
      (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival
      rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients.
      Increasing CAPRA scores were significantly associated with increasing risk of
      adverse pathologic outcomes. The c-index for CAPRA for the validation set was
      0.68, compared with 0.66 for the original development set. CONCLUSIONS: The UCSF
      CAPRA accurately predicted both biochemical and pathologic outcomes after radical
      prostatectomy among a large, diverse, cohort of men. These results validated the
      effectiveness of this powerful and straightforward instrument.

PMID- 17039506
TI  - Effect of cytoplast on the development of inter-subspecies nuclear transfer
      reconstructed goat embryo.
AB  - The aim of this study was to investigate effect of cytoplast on the development
      competence of reconstructed embryos derived from inter-subspecies somatic cell
      nucleus transfer (SCNT). First, the development potency of reconstructed embryos
      produced by transferring Boer goat fibroblast cell nucleus of different ages into
      enucleated Sannen goat ova was evaluated in order to determine which age of
      nuclear donor is favorable for the reconstructed embryos development. Secondly,
      the another component of reconstructed embryos, "cytoplast," was evaluated by
      comparing the effect of ovum cytoplast derived from Sannen male symbol x Boer
      female symbol descendant on the reconstructed embryos development to that of
      Sannen goat ovum cytoplast. The results revealed that the development rate of the
      reconstructed embryos derived from 2 months old Boer goat somatic cells was the
      highest, their gestation rate was up to 50%, and one viable male offspring was
      obtained. The cytoplast derived from the crossbreeding goats improves the
      development competence of reconstructed embryos, which birth rate was 5.5%. The
      genetic identification of offspring by using PCR-SSCP analysis confirmed that
      these cloned kids were derived from the donor. The results above reveal that the
      cytoplast of Sannen goat ovum could induce the dedifferentiation of somatic cell
      nuclei derived from Boer goat, but the reprogramming process of these
      reconstructed embryos seems incomplete, probably due to some incorrect processes
      happened after implantation. Relatedness components of nucleus donor in cytoplast
      of the crossbreeding goat may be helpful to induce the dedifferentiation of
      somatic cell nuclei completely and improve the development competence of the
      reconstructed embryos.

PMID- 17039507
TI  - Monte Carlo sampling of near-native structures of proteins with applications.
AB  - Since a protein's dynamic fluctuation inside cells affects the protein's
      biological properties, we present a novel method to study the ensemble of near
      native structures (NNS) of proteins, namely, the conformations that are very
      similar to the experimentally determined native structure. We show that this
      method enables us to (i) quantify the difficulty of predicting a protein's
      structure, (ii) choose appropriate simplified representations of protein
      structures, and (iii) assess the effectiveness of knowledge-based potential
      functions. We found that well-designed simple representations of protein
      structures are likely as accurate as those more complex ones for certain
      potential functions. We also found that the widely used contact potential
      functions stabilize NNS poorly, whereas potential functions incorporating local
      structure information significantly increase the stability of NNS.

PMID- 17039508
TI  - The StarClose Vascular Closure System: interventional results from the CLIP
      study.
AB  - BACKGROUND: The StarClose Vascular Closure System is a femoral access site
      closure technology that uses a flexible nitinol clip to complete a
      circumferential, extravascular arteriotomy close. The Clip CLosure In
      Percutaneous Procedures study was initiated to study the safety and efficacy of
      the StarClose device in subjects undergoing diagnostic and interventional
      catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596
      subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or
      standard compression of the arteriotomy after the percutaneous procedure. The
      study included roll-in (n = 113), diagnostic (n = 208), and interventional (n =
      275) arms with a primary safety endpoint of major vascular complications through
      30 days and a primary efficacy endpoint of postprocedure time to hemostasis.
      RESULTS: The results of the diagnostic StarClose cohort have been reported
      separately. Results for the interventional arm revealed major vascular
      complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual
      compression subjects (1/91; P = 1.00). No infections were seen in either cohort.
      Minor complications in the StarClose interventional group occurred at a rate of
      4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or
      arteriovenous fistula was not seen with StarClose. With StarClose, procedural
      success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the
      interventional group. Device success for the treatment group was 86.8%. In the
      interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain
      scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not
      statistically different. CONCLUSIONS: The clinical results of this study
      demonstrate that the StarClose Vascular Closure System is noninferior to manual
      compression with respect to the primary safety endpoint of major vascular events
      in subjects who undergo percutaneous interventional procedures. StarClose
      significantly reduced time to hemostasis, ambulation, and dischargeability when
      compared with compression.

PMID- 17039509
TI  - The safety and efficacy of the StarClose Vascular Closure System: the ultrasound
      substudy of the CLIP study.
AB  - BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular, Redwood City,
      CA) features a nitinol clip that is designed to achieve closure of the femoral
      arteriotomy access site. The CLIP Study was performed to assess the safety and
      efficacy of StarClose when compared with standard manual compression following 5
      6 French diagnostic or interventional percutaneous procedures. A substudy of this
      trial was designed to assess the utility of duplex ultrasonography to assess
      patency of the femoral artery and to determine access site complications
      (pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a
      multicenter prospective trial. This is the report of the duplex ultrasound (DUS)
      substudy of the CLIP trial. METHODS: A total of 17 U.S. sites enrolled 596
      subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or
      manual compression of the arteriotomy after a percutaneous procedure. The study
      included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275)
      arms with a primary safety endpoint of major vascular complications through 30
      days and a primary efficacy endpoint of postprocedure time to hemostasis. A
      substudy of the CLIP interventional arm evaluated DUS images of the closure site
      at five study sites, targeting 100 subjects at day 30 following hemostasis. The
      DUS protocol was devised and implemented by an independent vascular ultrasound
      core laboratory with extensive experience in vascular device trials. DUS inguinal
      region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was
      performed. A qualitative examination was performed to determine the presence of
      iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous
      fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional
      gray scale, color, and focused Doppler images. RESULTS: DUS of 96 subjects
      randomized to StarClose (n = 71) and compression (n = 25) were performed and
      evaluated. There was no evidence of hematoma, PSA, or AVF observed in the
      StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All
      patients in the substudy demonstrated patency of the access site artery and vein
      without thrombosis or stenosis. Finally, in the entire study cohort, no
      clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel
      thrombosis in the StarClose treated patients. CONCLUSION: DUS, a safe and
      reliable method for determining the safety and efficacy of access site closure
      devices, is a reliable, safe, inexpensive and accurate method of assessing
      vascular access site complications in multicenter trials. In this substudy of the
      CLIP study, DUS found no statistical difference in access site complications
      between the StarClose and manual compression groups. Both groups maintained
      vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV
      fistula.

PMID- 17039510
TI  - Sustained increased risk of adverse cardiac events over 5 years after
      implantation of gold-coated coronary stents.
AB  - OBJECTIVE: To study the 5-year outcome of patients treated with gold-coated stent
      placement. BACKGROUND: We have previously shown in the setting of a randomized
      trial that gold-coated stents are associated with worse mid-term outcome, mainly
      because of an increased risk of restenosis, compared to uncoated stents. The long
      term outcome and, in particular, mortality risk after implantation of gold-coated
      stents are not known. METHODS: A total of 731 patients with symptoms or signs of
      ischemia received randomly either a gold-coated (n = 367) or an uncoated steel
      stent (n = 364) of identical design. Patients were clinically followed-up at 1
      and 5 years. The primary endpoint of the study was the composite of major cardiac
      events (death, myocardial infarction, or target vessel revascularization (TVR)).
      The incidence of death was a secondary endpoint. RESULTS: Five-year follow-up was
      available in 97.5% of the patients. The composite of death, myocardial
      infarction, or TVR occurred in 51% of the patients treated with gold-coated
      stents and 40% of the patients treated with uncoated stents (P = 0.005). Of note,
      there was a marked increase in the absolute difference in mortality between
      patients in the gold-coated and uncoated stent groups, from 1.6% at 1 year to
      4.9% after 5-year follow-up (P = 0.09). A multivariate analysis showed that gold
      coated stent implantation was independently associated with 5-year mortality
      (hazard ratio, 1.46; 95% confidence interval, 1.02-2.09; P = 0.04). CONCLUSIONS:
      Gold-coated stents are associated with a sustained increased overall risk for
      major cardiac events, and notably, they may increase the long-term mortality
      risk.

PMID- 17039511
TI  - Iatrogenic left internal mammary artery-coronary vein anastomosis treated with
      covered stent deployment via retrograde percutaneous coronary sinus approach.
AB  - OBJECTIVES: Percutaneous treatment of acquired coronary fistula with covered
      stent BACKGROUND: Acquired aorto-coronary fistulae (ACF) is a rare complication
      of coronary artery bypass graft (CABG) surgery. Surgical repair has been
      generally recommended, but percutaneous techniques have also been described;
      coils were used primarily in smaller fistula while double umbrella or vascular
      occlusion devices were used in larger ones. To the best of our knowledge the use
      of coronary covered stent has never been reported. A 73-year-old man underwent
      CABG in November 2004 for unstable angina and left internal mammary artery (LIMA)
      was anastomosed to left anterior descending (LAD) coronary artery. Three months
      later he underwent a control angiogram to check for the reappearance of effort
      angina, which demonstrated an inadvertent LIMA-great cardiac vein (GCV)
      anastomosis. After discussions, an attempt to close the ACF with implantation of
      a covered stent was performed. METHODS: Using a percutaneous right internal
      jugular vein approach, coronary sinus was selectively cannulated and a 0.014-in.
      coronary guide wire was advanced selectively to the GCV, then a covered stent was
      deployed across the anastomotic site, obtaining the immediate occlusion of the
      ACF. RESULTS: No contrast medium flowed into the distal part of the GCV at the
      reinjection of the coronary sinus and a selective injection into LIMA showed the
      absence of flow through LIMA, confirming the occlusion of the anastomotic site.
      CONCLUSIONS: We have demonstrated successful occlusion of an iatrogenic ACF by
      using percutaneous stenting of GCV with covered stent via coronary sinus
      approach, which seems to be technically less demanding, safer, and time sparing.

PMID- 17039512
TI  - Stent thrombosis following the STAR technique in a complex RCA chronic total
      occlusion.
AB  - Four drug-eluting stents were deployed in the right coronary artery (RCA) of a
      symptomatic young woman who presented with a chronic total occlusion (CTO) of the
      RCA. The occlusion was successfully crossed using the recently described STAR
      technique. However, the patient died suddenly 15 hr later. Autopsy demonstrated a
      long segment of subintimal stenting in the proximal and mid RCA that was
      intraluminal in the distal vessel. Acute stent thrombosis in the subintimal
      stents was responsible for sudden death. This case highlights the potential risk
      of performing extensive subintimal stenting for CTO.

PMID- 17039513
TI  - Platelet GPIIb/IIIa antagonist, XV459, in heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a serious, immune-related complication
      of heparin therapy. One of the most severe manifestations of HIT is the
      development of thromboembolic events, which is based on platelet activation and
      aggregation caused by HIT-associated antibodies. Therapeutic options for patients
      with HIT are limited despite advancement toward the development of alternative
      (nonheparin) anticoagulants, such as direct thrombin inhibitors and indirect anti
      factor Xa agents. Platelet GPIIb/IIIa receptor antagonists have been shown to be
      the final common pathway for platelet aggregation regardless of the use of
      activator or anticoagulant. In this study, the ability of a novel platelet
      GPIIb/IIIa antagonist, a free acid form of roxifiban (XV459), to block platelet
      activation/aggregation in response to highly characterized heparin-PF4 antibody
      positive plasma/heparin was examined using light transmittance aggregometry,
      serotonin release, and (125)I-fibrinogen binding assays to human platelets. XV459
      at 20 nM maximally inhibited (P < 0.001) the platelet-activation/aggregation
      responses as mediated by the HIT antibody-positive plasma (in the presence of
      therapeutic heparin concentrations). Compared with controls, both HIT
      antibodies/heparin and TEAC (a mixture of thrombin [0.1 IU/ml], epinephrine [1
      microg/ml], arachidonate [0.1 mM], and collagen [10 microml]) resulted in
      significantly higher levels of fibrinogen binding to human platelets (5-7-fold
      increase; P < 0.001). Concentration-dependent profiles of XV459 on the mean
      percent inhibition of (125)I-fibrinogen binding in the presence of HIT antibodies
      and TEAC were achieved ( approximately 50% inhibition at 10 nM XV459). The
      platelet GPIIb/IIIa receptor antagonist (XV459) might be of potential benefit in
      the management of thrombotic thrombocytopenia produced by heparin and/or related
      glycosaminoglycans.

PMID- 17039514
TI  - Ad hoc percutaneous coronary interventions in patients with stable coronary
      artery disease--a study of prevalence, safety, and variation in use from the
      American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR).
AB  - OBJECTIVE: To utilize the American College of Cardiology National Cardiovascular
      Data Registry (ACC-NCDR) to monitor the performance and safety of ad hoc PCIs.
      BACKGROUND: The performance of ad hoc PCI remains controversial. Patients'
      preference, cost, and vascular access issues favor an ad hoc strategy. Adequate
      time for thoughtful decision-making, scheduling complexity, informed consent, and
      physician reimbursement favor PCI on a subsequent day. METHODS: We analyzed
      results in 68,528 patients with stable angina entered in the ACC-NCDR from 2001
      2003. Ad hoc PCI was evaluated in many clinical and nonclinical subgroups. A
      multivariable analysis was performed to determine whether ad hoc PCI had an
      independent relationship with complications or procedure success. RESULTS:
      Overall, 60.6% of patients underwent ad hoc PCI. There was no difference in ad
      hoc PCI mortality, renal failure, or vascular complications from staged PCI. A
      lower percentage of patients at high vs. low risk and with vs. without renal
      failure underwent ad hoc PCIs (58.6% vs.63.0% and 50.7% vs. 60.9% respectively).
      There was wide variation in the performance of ad hoc PCIs according to payer
      (70.2-60.3%), hospital PCI volume (67-50.2%), hospital owner (89.7-59.6%), and
      geographic area (75.5-47.4%). Ad hoc PCI per se was not independently related to
      PCI success or complications. CONCLUSIONS: PCI success was related to
      patient/lesion related factors and not to the performance of ad hoc PCIs per se.
      Although ad hoc PCI can be performed in more patients than at present, this
      strategy will never be possible in all patients at all times.

PMID- 17039515
TI  - Hypocholesterolemia in chronic anemias with increased erythropoietic activity.
AB  - Hypocholesterolemia of unknown etiology has been previously described in various
      chronic anemias. Few small studies also suggested that those patients have a
      lower incidence of atherosclerotic events. The aim of our study was to determine
      the extent of hypocholesterolemia in various types of anemias. We studied 59
      patients with chronic anemias associated with high-erythropoietic activity
      (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital
      spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired
      aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy
      controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin,
      soluble transferrin receptor (STR), and serum erythropoietin levels were
      determined in each patient. All patients with chronic anemia and increased
      erythropoietic activity had hypocholesterolemia, whereas none of those with low
      erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL
      cholesterol, and LDL cholesterol levels were found to be significantly lower in
      the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14
      mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001,
      respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01,
      respectively). Significant inverse correlation (R2=0.507) was observed between
      serum cholesterol and STR levels, which in the absence of iron deficiency reflect
      bone marrow activity. Taken together, our results imply that hypocholesterolemia
      accompanies anemias with high-erythropoietic activity. We suggest that the high
      erythropoitic activity-associated hypocholesterolemia is due to increased
      cholesterol requirements by the proliferating erythoid cells. Further studies are
      needed to elucidate the exact mechanism and the possible clinical consequences of
      this phenomenon.

PMID- 17039518
TI  - Simultaneous diagnostic coronary angiography utilizing a single arterial access
      technique.

PMID- 17039517
TI  - Coronary artery perforation during interventional procedures.

PMID- 17039520
TI  - Initial transcatheter palliation of hypoplastic left heart syndrome.
AB  - Initial percutaneous transcatheter palliation of hypoplastic left heart syndrome
      is now feasible. The primary procedures for palliation include stenting of the
      ductus arteriosus with a self expanding nitinol stent to secure an adequate
      systemic blood flow, placement of an internal pulmonary arterial band to protect
      the pulmonary vascular bed and to prevent pulmonary overcirculation, and widening
      of the interatrial communication by blade and balloon septostomy or static
      balloon dilation to decompress the left atrium. Anatomic variations of the ductus
      arteriosus have important implications for technical success with ductal
      stenting. Patients who have undergone complete transcatheter palliation with the
      internal pulmonary band appear to have less immediate morbidity at the time of
      transplant, with preserved integrity and growth of the branch pulmonary arteries
      at one year follow-up.

PMID- 17039519
TI  - Eph-ephrin A system regulates murine blastocyst attachment and spreading.
AB  - Although numerous adhesion molecules are expressed on mammalian endometrial
      epithelial cells, there have not been any studies of a mechanism to prevent
      premature attachment of the embryo. In this study, we examined the possible
      involvement of Eph-ephrin interaction, which can induce repulsive forces. In
      mice, Eph A1, A2, and A4 were expressed on endometrial epithelial cells and
      ephrin A1-4 on blastocysts. Reverse transcriptase-polymerase chain reaction
      showed that mRNA expression of ephrin A1-4 on embryos transiently decreased
      around the implantation period. Immunohistochemistry demonstrated that the
      expression of Eph A1 on endometrial epithelial cells and ephrin A1 and A3
      expression on embryos decreased at implantation sites. Recombinant Eph A1 reacted
      with cell the surface of ephrin A-bearing trophectoderm cells. Attachment assays
      using Eph A1-coated dishes showed that blastocyst attachment was reversibly
      inhibited by Eph A1. These findings suggest an important role of the Eph-ephrin A
      system in regulating the initial embryo-maternal contact during the cross-talk
      period that precedes embryo implantation.

PMID- 17039521
TI  - Development of a reexpandable covered stent for children.
AB  - The use of covered stents in children is limited by the need for a large long
      sheath for delivery and the impossibility of redilation once implanted. The
      authors developed a reexpandable covered stent implantable in children through a
      small sheath and evaluated its clinical feasibility in mini piglets. An original
      Palmaz stent was covered with a polyurethane membrane that could be stretched up
      to 700%. Under general anesthesia, the authors implanted the covered stents in
      six mini piglets using a long sheath with a diameter approximately 1 French
      larger than the recommended size required to deliver an uncovered Palmaz stent.
      The implantation technique was similar to conventional stent implantation. In six
      piglets, the stent could be redilated from 7.5 to 8.7 mm 28-70 days after
      implantation. Macroscopic and microscopic examination showed intimal coverage of
      the coating with minimal inflammatory reaction around the stent. Our newly
      designed reexpandable stent covered with a polyurethane membrane is promising for
      use in children.

PMID- 17039522
TI  - New clothes for covered stents.

PMID- 17039523
TI  - Behavior of enteric neural crest-derived cells varies with respect to the
      migratory wavefront.
AB  - Neural crest-derived cells colonize the entire gastrointestinal tract. The
      migration of these enteric neural crest-derived cells (ENCCs) occurs by their
      formation of cellular strands that extend into the intestinal mesenchyme. We have
      studied the behavior of crest cells that underlies the formation and extension of
      these strands by time-lapse microscopy. ENCCs expressing fluorescent marker
      molecules were visualized in situ in the embryonic mouse and chick gut. The major
      contributor to strand extension is from cells located within a region
      approximately 300 microm behind (rostral to) the most caudal cells in the
      migratory wavefront. Cells in the region immediately behind the leading cell of
      the strand either move intermittently in parallel with the leading cell, or
      advance caudally toward the wavefront over other ENCCs. Another addition to the
      strands arises from isolated cells located caudal to the wavefront. These cells
      showed a range of behavior including attachment and separation from the strands.
      The extending strands converged to form nodes, and then diverged along
      independent paths to form new strands, a behavior suggestive of attraction and
      repulsion. This behavior is probably responsible for the unique reticulated
      arrangement of ganglia in the enteric nervous system. As cells become positioned
      farther behind the wavefront, they exhibit more restricted movement and varied
      trajectories. We conclude that ENCCs exhibit different behaviors, depending on
      their position with respect to the wavefront. These different behaviors suggest a
      critical role for cell-cell interaction in the migratory process.

PMID- 17039524
TI  - Transcatheter patent foramen ovale closure using the Premere PFO occlusion
      system.
AB  - OBJECTIVES: To evaluate the safety and efficacy profile of the new Premere patent
      foramen ovale (PFO) occlusion system. BACKGROUND: Several different devices have
      been used so far for transcatheter PFO closure but no data has been published so
      far on the efficacy and safety of the Premere PFO occlusion system. METHODS:
      Since September 2005, 15 patients (seven males, eight females; mean age 51.2 +/-
      10.8 years) at our institution underwent transcatheter PFO closure because of
      cryptogenic stroke, using the Premere PFO occlusion system. The procedure was
      performed under fluoroscopic and transesophageal echocardiographic (TEE) guidance
      in all patients. Seven patients (47%) had an associated atrial septal aneurysm
      and two patients had had >1 stroke. Five patients (33%) had an associated
      thrombophilia, whereas three patients (20%) had a diagnosis of migraine headache
      with aura, by the referring neurologist. Residual shunt was assessed immediately
      after and 1 month (only in 11 patients) after the procedure by both transcranial
      Doppler and TEE. RESULTS: Premere PFO devices could be implanted in all patients
      (20 mm size in seven patients, 25 mm size in eight). Fluoroscopy time was 7.3 +/-
      1.9 and procedural time was 11 +/- 3 min (range 7-17 min), reflecting our initial
      learning curve with this device. No complication occurred during the procedure or
      at follow-up. A residual shunt was noted immediately after the procedure in eight
      patients (53%) and at 1 month in 4/11 patients (36%). Residual shunt was mild in
      all patients. After a median follow-up of 4.2 months (0.2-5.8 months), no patient
      had a recurrent stroke. All patients with migraine headache with aura had
      resolution of symptoms. CONCLUSIONS: Our preliminary experience with the Premere
      PFO occlusion system shows that this device is safe and effective.

PMID- 17039525
TI  - Transcatheter closure versus medical therapy of patent foramen ovale and
      cryptogenic stroke.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of
      device closure of patent foramen ovale (PFO) versus antiplatelet therapy in
      patients with cryptogenic stroke (CS). BACKGROUND: There are no controlled data
      to support the therapeutic value of PFO closure with a device compared to medical
      treatment in patients with CS. METHODS: We performed a nonrandomized,
      prospective, patient preference case series comparing the recurrence rate in 92
      patients with PFO and CS who were treated either with antiplatelet agents (44
      patients) or underwent catheter closure (48 patients) using the Amplatzer PFO
      occluder (APFOO). All patients completed a 2-year follow-up. RESULTS: PFO closure
      group. Immediate complete closure (CC) was observed in 44/48 (91%) patients. Four
      (9%) patients had a minimal residual shunt immediately after the procedure. One
      patient developed hemopericardium that was successfully managed by
      pericardiocentesis. No other complication was observed. Follow-up. PFO closure
      group. Contrast bubble study at 6-month follow-up confirmed CC in all 48
      patients. No complications were observed. Antiplatelet therapy group. Three (6%)
      and 6 (13%) patients had a major and minor hemorrhagic event, respectively. The
      average incidence of embolic events/year was 0 and 14.75% for the PFO closure
      group and the antiplatelet therapy group, respectively (P < 0.001). CONCLUSIONS:
      PFO closure using the APFOO is a rational alternative to medical treatment in
      patients with CS. Larger randomized clinical trials are required to support the
      use of this device over the other PFO occluders and medical therapy.

PMID- 17039526
TI  - Suture-mediated closure of a patent foramen ovale during surgery without
      cardiopulmonary bypass.
AB  - A patent foramen ovale (PFO) is associated with an increased risk of recurrent
      ischemic strokes and transient ischemic attacks due to paradoxical emboli in
      patients with prior neurological events. We report a case of a surgical suture
      mediated of a PFO closure without cardiopulmonary bypass in a patient with
      recurrent cerebral ischemic events, who was intolerant of medical therapy, was a
      poor candidate for catheter-based PFO closure, and presented as a potentially
      high risk for poor wound healing from traditional surgical closure.

PMID- 17039527
TI  - Transcatheter closure of aortic sinus to left atrial fistula caused by erosion of
      Amplatzer septal occluder.
AB  - One year after Amplatzer device closure of an atrial septal defect, an aortic to
      left atrial fistula was diagnosed in a patient who developed a new onset murmur
      with no other symptoms. The fistula was closed with a 4-mm Amplatzer Septal
      Occluder during a transcatheter procedure, avoiding the need for cardiac surgical
      repair.

PMID- 17039528
TI  - Late migration of a Sideris buttoned device for occlusion of atrial septal
      defect.
AB  - We describe a 17-year-old patient with an atrial septal defect who underwent
      device closure with a second generation Sideris buttoned device at 4 years of
      age. She presented 13 years after the procedure with the acute onset of chest
      discomfort, at which time a chest radiograph showed migration of the wire of the
      right atrial counter-occluder to the lateral aspect of the right atrial wall,
      with an associated right atrial perforation. The patient underwent uneventful
      surgical device retrieval and atrial septal defect closure. Late migration of a
      portion of the Sideris buttoned device can occur, suggesting the need for
      continued follow up, and a high index of suspicion for device failure should a
      patient become symptomatic.

PMID- 17039529
TI  - An 84-year-old patient with an atrial septal defect rescued using the Amplatzer
      septal occluder device.
AB  - We report the case of a rescued 84-year-old patient with atrial septal defect
      (ASD) who was emergently admitted to our intensive care unit with progressive
      dyspnea requiring mechanical ventilation for severe anoxia and respiratory
      arrest. She had no history of congenital heart diseases. ECG and chest X-ray
      revealed overload of the right atrium and ventricle, and severe increase in
      pulmonary vascular markings. Transesophageal echocardiography showed a moderately
      large size ASD (18 x 23 mm(2)). Hemodynamic evaluation documented an increase in
      PA pressure of 37/16 mm Hg and Q(p)/Q(s) of 2.33. Her systemic condition did not
      improve following diuretics, cathecholamine, and afterload-reducing substances.
      She required mechanical ventilation for severe hypoxia. She underwent successful
      closure of the ASD using an Amplatzer septal occluder on day 17. Hemodynamics and
      findings on chest X-ray dramatically improved after this procedure. She was
      discharged from the hospital on foot.

PMID- 17039530
TI  - Failure of cutting balloon angioplasty to prevent restenosis in childhood
      pulmonary venous stenosis.
AB  - We describe bilateral pulmonary vein stenosis in a 5-year-old boy. He initially
      presented with haemoptysis secondary to left upper lobe pulmonary vein atresia
      and left lower lobe stenosis and subsequently he underwent left-sided
      pneumonectomy. He underwent repeat cardiac catheterizations with repeated balloon
      angioplasty of the right-sided venous stenoses using a cutting balloon. Despite
      satisfactory initial results the pulmonary venous stenosis reoccurred as early as
      2 months following balloon angioplasty. Although cutting balloon angioplasty has
      demonstrated effective immediate alleviation of pulmonary venous stenosis its
      utility in providing sustained improvement in pulmonary vein stenosis is limited.

PMID- 17039531
TI  - Failure of cutting balloon angioplasty to prevent restenosis in childhood
      pulmonary vein stenosis.

PMID- 17039532
TI  - Reproducible microvascular dysfunction with dobutamine infusion in Takotsubo
      cardiomyopathy presenting with ST segment elevation.
AB  - Takotsubo (ampulla) cardiomyopathy, or broken heart syndrome, is an
      underrecognized cardiac illness that usually presents as an acute coronary
      syndrome in postmenopausal females. The disorder is frequently associated with
      episodes of mental or physical stress, implicating an abnormal cardiac response
      to increased catecholamines. Although death has been reported during the index
      event, the long-term prognosis is good with full recovery of left ventricular
      function. We present a case of Takotsubo cardiomyopathy mimicking anterior ST
      segment elevation myocardial infarction precipitated by dobutamine stress
      testing. Reinfusion of dobutamine in the catheterization laboratory reproduced
      symptoms with angiography and intravascular ultrasound supporting the theory of
      abnormal microvascular circulation as the etiology of Takotsubo cardiomyopathy.
      Acute and delayed magnetic resonance imaging demonstrated no infarction with
      complete recovery of ventricular function.

PMID- 17039533
TI  - Improvement of biventricular function after transcatheter closure of atrial
      septal defect: a case report.
AB  - We report a 17-year-old man presented with palpitation. Echocardiography
      demonstrated secundum atrial septal defect (ASD) with marked right sided
      dilatation, indicating significant left to right intracardiac shunting. Cardiac
      magnetic resonance imaging performed 3 months after transcatheter ASD closure
      demonstrated marked improvement in biventricular systolic function.

PMID- 17039534
TI  - Specific integrin subunits in bovine oocytes, including novel sequences for alpha
      6 and beta 3 subunits.
AB  - Integrins facilitate attachment of cells to the extra-cellular matrix, often
      binding the arginine-glycine-aspartic acid tri-peptide motif, thus facilitating
      cell migration, mediating cell-cell adhesion, linking the extracellular matrix
      (ECM) with cytoskeletal elements, and acting as signaling molecules. Adhesion
      activates signaling mechanisms that regulate integrin function, cytoskeletal
      assembly, cell behavior, and protein synthesis. Immunofluorescence was used to
      determine the presence of integrin alpha and beta subunits on the surface of
      bovine oocytes using a panel of monoclonal antibodies (mAbs) specific for alphaL,
      alphaM, alphaX, alphaV, alpha2, alpha4, alpha6, beta1, beta2, and beta3 antigens,
      with multiple antibodies for each subunit. Confocal microscopy indicated the
      presence of alphaV, alpha6, alpha4, alpha2, ss1, and ss3 integrin subunits on the
      plasma membrane of bovine oocytes. The presence of these subunits was verified by
      RT-PCR analysis using primers designed based on known gene sequences of bovine
      integrin subunits, or by using sequence information using bovine expressed
      sequence tags (EST) compared with known human and murine integrin subunit gene
      sequence information. Previously unpublished sequence information for bovine
      alpha6 and beta3 integrins was determined. The presence of these integrin
      subunits on the bovine oocyte vitelline membrane supports the hypothesis that
      sperm-oocyte interactions in the bovine are mediated by integrins.

PMID- 17039535
TI  - Donor cell differentiation, reprogramming, and cloning efficiency: elusive or
      illusive correlation?
AB  - Compared to other assisted reproductive technologies, mammalian nuclear transfer
      (NT) cloning is inefficient in generating viable offspring. It has been
      postulated that nuclear reprogramming and cloning efficiency can be increased by
      choosing less differentiated cell types as nuclear donors. This hypothesis is
      mainly supported by comparative mouse cloning experiments using early
      blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic
      donor cells. We have re-evaluated these comparisons, taking into account
      different NT procedures, the use of donor cells from different genetic
      backgrounds, sex, cell cycle stages, and the lack of robust statistical
      significance when post-blastocyst development is compared. We argue that while
      the reprogrammability of early blastomeres appears to be much higher than that of
      somatic cells, it has so far not been conclusively determined whether
      differentiation status affects cloning efficiency within somatic donor cell
      lineages.

PMID- 17039536
TI  - Transcatheter closure of secundum atrial septal defects.

PMID- 17039537
TI  - Diagnostic utility of the two methods of ankle brachial index in the detection of
      peripheral arterial disease of lower extremities.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a common disease that is
      diagnosed with a screening test called the Ankle Brachial Index (ABI). Different
      methods of ABI have been described in the literature. We wanted to estimate and
      compare the sensitivity and specificity of an alternative method of calculating
      the ABI (LAP ABI, low ankle pressure ABI) with the current method (named high
      ankle pressure (HAP)), using digital subtraction angiography (DSA) as the gold
      standard. METHODS: We reviewed the records of all patients who had undergone DSA
      at a major academic center between August 2003 and October 2005. The study
      includes 107 patients/208 limbs. Inclusion criteria included patients with an ABI
      performed within 30 days prior to the DSA. Patients with non-compressible vessels
      and ABI >1.40 were excluded. Abnormal ABI was defined as < or = 0.9 for both
      methods. Disease on angiogram was defined as the presence of 50% or more stenosis
      of any lower extremity artery from the aorto-iliac bifurcation to the ankle
      arteries. RESULTS: The sensitivity of the HAP and LAP ABI for the diagnosis of
      PAD was 69 and 84%, respectively (P < 0.001). The specificity of the HAP and the
      LAP method was 83 and 64% respectively (P < 0.01). The overall accuracy of LAP
      ABI and HAP ABI was 80 and 72%, respectively. CONCLUSIONS: The LAP ABI has better
      sensitivity and overall accuracy in comparison to the HAP ABI to diagnose PAD.

PMID- 17039539
TI  - Percutaneous closure of a para-anastomotic abdominal aortic graft leak.
AB  - Para-anastomotic graft leaks are a potential complication following surgical
      repair of an aortic aneurysm. Reoperation may be associated with significant
      morbidity and mortality. We report successful percutaneous transcatheter closure
      of an anastomotic graft leak utilizing an occluder device.

PMID- 17039538
TI  - Sirolimus for below the knee lesions: mid-term results of SiroBTK study.
AB  - OBJECTIVES: To assess the safety and efficacy of sirolimus-eluting stents (SESs)
      in the treatment of severe intermittent claudication and critical limb ischaemia
      with "below-the-knee" lesions, unsuitable for surgery. BACKGROUND: Limited
      published evidence suggests that drug-eluting stents may offer significant
      improvements in the treatment of infrapopliteal lesions. METHODS: Thirty
      consecutive patients with either severe intermittent claudication or critical
      limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel
      disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES.
      Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of
      patients were male and 36% diabetic. The primary endpoint was clinical
      improvement and healing of ulcers at short term (1 month) and mid term (7.7
      months). The secondary endpoint was primary vessel patency rate (angiographic or
      duplex assessment). All patients received clopidogrel (75 mg daily) or
      ticlopidine (150 mg daily) for 2 months or longer. RESULTS: Angiographic and
      procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it
      was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb
      salvage was obtained in 100% of patients. Other events were: two cardiac deaths
      unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome,
      one contralateral CLI, and three recurrent homolateral claudication cases. All
      surviving patients had a mid-term clinical improvement with 97% of primary
      patency (56 patent arteries on 58 arteries). CONCLUSION: Treatment of "below-the
      knee" lesions with SES may provide an alternative treatment for patients with
      CLI.

PMID- 17039540
TI  - Update of carotid stent trials.
AB  - As is the case in many vascular territories, endovascular treatment of
      extracranial carotid artery disease is becoming a rival alternative to surgery.
      Results of carotid artery stenting (CAS) are improving with the introduction of
      embolic protection devices, improved technology, and increasing operator
      experience. Multiple clinical studies have shown results in favor of CAS as
      opposed to carotid endarterectomy (CEA) in patients considered at high risk for
      surgery. Current ongoing trials are examining both treatment options in low and
      intermediate risk patients in prospective randomized protocols. With the recent
      FDA approval of carotid stent systems, we are entering a new era in the treatment
      of carotid artery disease. An update of modern carotid stent studies, as well as
      stent versus surgery studies in the current era is needed.

PMID- 17039541
TI  - Gadolinium-based contrast agents and nephrotoxicity.

PMID- 17039544
TI  - The Cath Lab Crew: your second family.

PMID- 17039546
TI  - Systematic comparison of catalytic mechanisms of hydrolysis and transfer
      reactions classified in the EzCatDB database.
AB  - Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and
      transferases, were analyzed based on their enzyme structures. A method of
      systematic comparison and classification of the catalytic reactions was
      developed. Hydrolysis and transfer reactions closely resemble one another,
      displaying common mechanisms, single displacement, and double displacement. These
      displacement mechanisms might be further subclassified according to the type of
      catalytic factors and nucleophilic substitution involved. Several types of
      catalytic factors exist: nucleophile, acid, base, stabilizer, modulator,
      cofactors. Nucleophilic substitution might be categorized as S(N)1/S(N)2 (or
      dissociative/associative) reactions. The classification indicates that some
      mechanisms favor particular types of catalytic factors. In hydrolyses of amide
      bonds and phosphoric ester bonds, mechanisms with single displacement tend to use
      inorganic cofactors such as zinc and magnesium ions as important catalysts,
      whereas those with double displacement frequently do not use such cofactors. In
      contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one
      exception. The trypsin-like hydrolytic reaction, which is catalyzed by the
      classic catalytic triad comprising serine/histidine/aspartate, can be considered
      as a "super-reaction" because it is observed in at least three nonhomologous
      enzymes, whereas most reactions are singlets without any nonhomologous enzymes.
      By dividing complex reactions into several reactions, correlations between active
      site structures and catalytic functions can be suggested. This classification
      method is applicable to other reactions such as elimination and isomerization.
      Furthermore, it will facilitate annotation of enzyme functions from 3D patterns
      of enzyme active sites. The classification is available at
      http://mbs.cbrc.jp/EzCatDB/RLCP/index.html.

PMID- 17039547
TI  - Computational basis of knowledge-based conformational probabilities derived from
      local- and long-range interactions in proteins.
AB  - The probabilities of the various basins in Ramachandran maps are examined
      critically. The theoretical basis of probability calculations both from molecular
      computations and from protein libraries are discussed. The well-defined basins of
      the Ramachandran maps are treated as rotational isomeric states. Statistical
      independence and dependence of the states of different residues along the peptide
      chain are discussed. The Flory isolated pair hypothesis, near neighbor
      correlations, context effects, and long-range correlations are examined
      critically. A method of evaluating long-range correlations in helical and
      extended sequences is introduced in analogy with earlier polymer theory. Three
      different protein libraries are constructed where data is considered from
      residues in the (i) coiled regions, (ii) all regions, and (iii) only the helical
      and extended regions of proteins. Singlet and pairwise dependent probabilities
      calculated from these libraries are used to predict whether a given sequence is
      helical or extended. Predictions using pairwise dependence were not better than
      those using singlet probabilities. Modeling of long-range correlations improved
      the predictions significantly. Removal of the Chameleon sequences from the data
      set also improved the predictions, but to a lesser extent.

PMID- 17039548
TI  - FiberID--a technique to identify fibrous protein subclasses.
AB  - Fibrous proteins such as collagen, silk, and elastin play critical biological
      roles, yet they have been the subject of few projects that use computational
      techniques to predict either their class or their structure. In this article, we
      present FiberID, a simple yet effective method for identifying and distinguishing
      three fibrous protein subclasses from their primary sequences. Using a
      combination of amino acid composition and fast Fourier measurements, FiberID can
      classify fibrous proteins belonging to these subclasses with high accuracy by
      using two standard machine learning techniques (decision trees and Naive Bayesian
      classifiers). After presenting our results, we present several fibrous sequences
      that are regularly misclassified by FiberID as sequences of potential interest
      for further study. Finally, we analyze the decision trees developed by FiberID
      for potential insights regarding the structure of these proteins.

PMID- 17039549
TI  - Origin and characteristics of glycogen cells in the developing murine placenta.
AB  - The junctional zone (Jz) of the mouse placenta consists of two main trophoblast
      populations, spongiotrophoblasts and glycogen cells (GCs), but the development
      and function of both cell types are unknown. We conducted a quantitative analysis
      of GC size, number, and invasion of cells into the decidua across gestation.
      Furthermore, we identified markers of GC function to investigate their possible
      roles in the placenta. While the spongiotrophoblast cell volume doubles, and cell
      number increases steadily from E12.5 to E16.5, there is a remarkable 80-fold
      increase in GC numbers. This finding is followed by a notable decrease by E18.5.
      Surprisingly, the accumulation of GCs in the decidua did not fully account for
      the decrease in GC number in the Jz, suggesting loss of GCs from the placenta.
      Glucagons were detected on GCs, suggesting a steady glucose release throughout
      gestation. Connexin31 staining was shown to be specific for GCs. GC migration and
      invasion may be facilitated by temporally regulated expression of matrix
      metalloproteinase 9 and the imprinted gene product, Decorin. Expression of the
      clearance receptor for type II insulin-like growth factor (IGF-II), IGF2R, in a
      short developmental window before E16.5 may be associated with regulating the
      growth effects of IGF-II from glycogen cells and/or labyrinthine trophoblast on
      the expansion of the Jz. Thus stereology and immunohistochemistry have provided
      useful insights into Jz development and function of the glycogen cells.

PMID- 17039551
TI  - Hydrogen peroxide synthesis: an outlook beyond the anthraquinone process.
AB  - Hydrogen peroxide (H2O2) is widely used in almost all industrial areas,
      particularly in the chemical industry and environmental protection. The only
      degradation product of its use is water, and thus it has played a large role in
      environmentally friendly methods in the chemical industry. Hydrogen peroxide is
      produced on an industrial scale by the anthraquinone oxidation (AO) process.
      However, this process can hardly be considered a green method. It involves the
      sequential hydrogenation and oxidation of an alkylanthraquinone precursor
      dissolved in a mixture of organic solvents followed by liquid-liquid extraction
      to recover H2O2. The AO process is a multistep method that requires significant
      energy input and generates waste, which has a negative effect on its
      sustainability and production costs. The transport, storage, and handling of bulk
      H2O2 involve hazards and escalating expenses. Thus, novel, cleaner methods for
      the production of H2O2 are being explored. The direct synthesis of H2O2 from O2
      and H2 using a variety of catalysts, and the factors influencing the formation
      and decomposition of H2O2 are examined in detail in this Review.

PMID- 17039552
TI  - Detection of nitric oxide release from single cells by using constant-distance
      mode scanning electrochemical microscopy.

PMID- 17039550
TI  - Candidate regulators of mammary branching morphogenesis identified by genome-wide
      transcript analysis.
AB  - The mammary gland develops in a process known as branching morphogenesis, whereby
      a distal epithelial bud extends and bifurcates to form an extensive ductal
      network. Compared with other branched organs, such as the lung and kidney, little
      is known about the molecular basis of branching in the mammary gland. Here we
      report a microarray profiling strategy to identify novel genes that may regulate
      mammary branching. We microdissected terminal end bud (TEB) and mature duct
      microenvironments from beta-actin-green fluorescent protein reporter mice and
      compared their RNA expression profiles with epithelium-free mammary stroma by
      means of microarray. We identified 1,074 genes enriched in the TEB
      microenvironment, 222 genes enriched in the mature duct microenvironment, and 385
      genes enriched in both TEB and mature duct microenvironments. The microarray
      correctly predicted the expression of genes known to be enriched in the
      epithelium (Ets-5) and stroma (MMP-14) of TEBs and in the mature duct
      microenvironment (MMP-3). The microarray also correctly predicted the
      localization of previously uncharacterized genes, such as the TEB-enriched SPRR
      1a, the duct-enriched casein-gamma, and the general epithelial marker
      pleiotrophin. Analysis of genes enriched in TEBs revealed several genes in the
      Wnt (Wnt-2, Wnt-5a, Wnt-7b, Dsh-3, Frizzled-1, Frizzled-2), hedgehog (Dhh),
      ephrin (Ephrin-B1, Eph-A2), and transcription factor (Twist-1, Twist-2, Snail)
      families. In situ hybridization verified that these genes were enriched in the
      TEB epithelium (Wnt-5a, Wnt-7b, Dhh, Eph-A2) or TEB stroma (Wnt-2, Frizzled-1,
      Ephrin-B1). We discuss the potential roles of these genes in mammary branching
      morphogenesis.

PMID- 17039553
TI  - Polymer brushes as ionotropic matrices for the directed fabrication of
      microstructured calcite thin films.

PMID- 17039554
TI  - Tailor-made onionlike stereocomplex crystals in incompatible, enantiomeric,
      polylactide-containing block copolymer blends.

PMID- 17039555
TI  - A highly reactive and stereoselective beta-mannopyranosylation system: mannosyl 4
      pentenoate/PhSeOTf.

PMID- 17039556
TI  - A tosylimido analogue of a nonheme oxoiron(IV) complex.

PMID- 17039557
TI  - Cyclic carbodiphosphorane-diphosphinocarbene thermal interconversion.

PMID- 17039558
TI  - Catalytic enantioselective domino oxa-michael/aldol condensations: asymmetric
      synthesis of benzopyran derivatives.
AB  - The first direct organocatalytic asymmetric domino oxa-Michael/aldol condensation
      reaction is presented. The unprecedentedly simple, chiral, pyrrolidine-catalyzed
      asymmetric domino reactions between salicylic aldehyde derivatives and alpha,beta
      unsaturated aldehydes proceed with high chemo- and enantioselectivities to give
      the corresponding chromene-3-carbaldehyde derivatives in high yields and with ee
      values of 83-98%.

PMID- 17039559
TI  - Direct catalytic enantioselective alpha-aminomethylation of aldehydes.
AB  - The direct catalytic asymmetric alpha-aminomethylation of aldehydes is presented.
      The chiral amine and amino acid catalyzed reactions between unmodified aldehydes
      and a formaldehyde-derived imine precursor were fast and proceeded with high
      chemo- and enantioselectivities. The corresponding dibenzyl-protected gamma-amino
      alcohols were isolated in high yields with up to 98% ee after in situ reduction.
      The reaction is a novel entry to valuable beta(2)-amino acid derivatives.

PMID- 17039560
TI  - On the first polyarsenic organic compound from nature: arsenicin A from the New
      Caledonian marine sponge Echinochalina bargibanti.
AB  - Reported here is the first polyarsenic compound ever found in nature. Denominated
      arsenicin A, it was isolated along a bioassay-guided fractionation of the organic
      extract of the poecilosclerid sponge Echinochalina bargibanti collected from the
      north-eastern coast of New Caledonia. In defining an adamantine-type polyarsenic
      structure for this compound, deceptively simple NMR spectra were complemented by
      extensive mass spectral analysis. However, it was only the synthesis of a model
      compound that provided the basis to discriminate structure 4 from other
      spectrally compatible structures for arsenicin A; to this end, a comparative ab
      initio simulation of IR spectra for the natural and the synthetic compounds was
      decisive. Arsenicin A is endowed with potent bactericidal and fungicidal
      activities on human pathogenic strains. All this may revive pharmacological
      interest in arsenic compounds while prompting us to rethink the arsenic cycle in
      nature.

PMID- 17039561
TI  - Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl
      ketones catalyzed by bifunctional organocatalysts.
AB  - A highly enantioselective Michael addition of alpha-substituted cyanoacetates to
      vinyl ketones was accomplished in the presence of simple bifunctional
      thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl
      cyanoacetates have been successfully applied to give multifunctional compounds
      with an all-carbon-substituted quaternary stereocenter in excellent
      enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts
      could be smoothly converted to variously structured beta(2,2)-amino acid esters.
      Moreover, an interesting reaction model involving multiple hydrogen-bonding
      interactions amongst the thiourea/tertiary amine catalyst and the reactants has
      been proposed based on the absolute configuration of the adduct and computational
      studies.

PMID- 17039563
TI  - NFAT transcription factors in control of peripheral T cell tolerance.
AB  - The Ca++-regulated calcineurin/NFAT cascade is one of the crucial signalling
      pathways that controls adaptive immunity. However, a number of novel experimental
      data suggest that, in addition to their role in T cell activation, NFATc
      transcription factors play also a decisive role in the generation of peripheral
      tolerance against self-antigens. This function of NFATc factors is mediated by
      controlling activation-induced cell death and clonal anergy of T helper cells and
      the activity of regulatory T cells. The multi-functional role of NFATc proteins
      characterize these transcription factors as key regulators of immunological
      tolerance and, if dysregulated, of development of autoimmune diseases.

PMID- 17039562
TI  - Highly efficient syntheses of hyaluronic acid oligosaccharides.
AB  - Highly efficient syntheses of hyaluronic acid oligosaccharides have been
      accomplished through the pre-activation based iterative one-pot strategy. A
      series of oligosaccharides ranging from di- to hexasaccharides were rapidly
      assembled using only near stoichiometric amounts of the building blocks without
      aglycon adjustment or purifications of intermediate oligosaccharides.
      Deprotection and oxidation protocols were developed for protective group removal
      and oxidation-state adjustment. The availability of such structurally well
      defined synthetic hyaluronic acid oligosaccharides will greatly facilitate the
      establishment of detailed structure-function relationships.

PMID- 17039564
TI  - Cross-presentation of antigens from apoptotic tumor cells by liver sinusoidal
      endothelial cells leads to tumor-specific CD8+ T cell tolerance.
AB  - Development of tumor-specific T cell tolerance contributes to the failure of the
      immune system to eliminate tumor cells. Here we report that hematogenous
      dissemination of tumor cells followed by their elimination and local removal of
      apoptotic tumor cells in the liver leads to subsequent development of T cell
      tolerance towards antigens associated with apoptotic tumor cells. We provide
      evidence that liver sinusoidal endothelial cells (LSEC) remove apoptotic cell
      fragments generated by induction of tumor cell apoptosis through hepatic NK1.1+
      cells. Antigen associated with apoptotic cell material is processed and cross
      presented by LSEC to CD8+ T cells, leading to induction of CD8+ T cell tolerance.
      Adoptive transfer of LSEC isolated from mice challenged previously with tumor
      cells promotes development of CD8+ T cell tolerance towards tumor-associated
      antigen in vivo. Our results indicate that hematogenous dissemination of tumor
      cells, followed by hepatic tumor cell elimination and local cross-presentation of
      apoptotic tumor cells by LSEC and subsequent CD8+ T cell tolerance induction,
      represents a novel mechanism operative in tumor immune escape.

PMID- 17039565
TI  - Mice expressing high levels of soluble CD14 retain LPS in the circulation and are
      resistant to LPS-induced lethality.
AB  - Despite significant progress in understanding the origin of soluble CD14 (sCD14),
      its physiological function remains largely unknown. Recent research has produced
      contradictory observations suggesting that sCD14 may have either beneficial or
      detrimental properties in protection against LPS-induced endotoxin shock. To
      resolve this controversy and to establish a mouse model suitable for elucidation
      of the functions of human CD14 (hCD14) in vivo, we generated several lines of
      transgenic mice bearing different copy numbers of the hCd14 transgene on a murine
      Cd14-/- background. The hCD14 was entirely capable of complementing loss of mouse
      CD14 to mediate cellular responses to LPS. Serum levels of sCD14 in a founder
      with multiple copies of the transgene were several times higher than in
      transgenic animals with a single copy of Cd14. Furthermore, mice with high levels
      of hCD14 were hypo-responsive to LPS and survived a lethal dose of LPS. Further
      inquiry into the mechanism of the hypo-response to LPS revealed that protection
      is associated with the higher amounts of circulating LPS. Most of this
      circulating LPS can be immunoprecipitated with anti-CD14 antibodies. These
      results suggest that sCD14 blocks circulating LPS by limiting the amount of
      monocyte-bound LPS and thus reduces inflammatory responses.

PMID- 17039566
TI  - The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental
      autoimmune uveoretinitis.
AB  - ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and
      plays differential roles in autoimmune diseases. In this study, we examined the
      role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune
      uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression
      was found on infiltrating CD4+ T cells in the region of the retina in EAU-induced
      mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice
      showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1
      interaction during the effector phase ameliorated the disease, whereas its
      blockade during the induction phase exhibited no significant effect. Moreover,
      administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by
      adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited
      the expansion and/or effector function of pathogenic T cells, given that
      proliferative response and IFN-gamma production by lymph node cells were reduced
      upon restimulation with the antigen peptide in vitro. These results suggest that
      the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis.
      We also indicated that ICOS-mediated costimulation plays differential roles in
      EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease
      induced in the same manner as EAU.

PMID- 17039567
TI  - A critical role for ICOS co-stimulation in immune containment of pulmonary
      influenza virus infection.
AB  - Lung pathology observed during influenza infection is due to direct damage
      resulting from viral replication and bystander damage caused by overly exuberant
      antiviral immune mechanisms. In the absence of universally effective vaccines and
      antiviral therapies, knowledge of the cellular components required for immune
      containment of influenza is essential. ICOS is a late co-stimulatory molecule
      expressed by T cells 12-24 h after activation. We show for the first time that
      inhibition of ICOS with a monoclonal antibody reduces pulmonary T cell
      inflammation and associated cytokine expression. Surprisingly however, this
      reduction in T cells was not accompanied by an alleviation of weight loss and
      illness. Furthermore, lung viral titres were elevated following anti-ICOS
      treatment, suggesting that the beneficial outcome of reducing T cell pathology
      was masked by enhanced virus-induced damage and innate inflammation. This study
      demonstrates the delicate balance that exists between pathogen burden and
      pulmonary T cell inflammation during influenza infection and highlights the
      critical role of ICOS in this response.

PMID- 17039568
TI  - In vivo CD44-CD49d complex formation in autoimmune disease has consequences on T
      cell activation and apoptosis resistance.
AB  - CD44 is involved in leukocyte migration and activation and has recently been
      reported to contribute to leukocyte extravasation by associating with CD49d. We
      explored whether similar changes in CD44 activity are seen in vivo using murine
      alopecia areata (AA) as a chronic, organ-related autoimmune disease model system.
      Expression of the activated, hyaluronan-binding form of CD44, and of CD49d, was
      elevated in draining lymph node cells (LNC) of AA-affected mice as compared to
      control mice. LNC of AA mice displayed increased motility, proliferative activity
      and apoptosis resistance, which were equally well inhibited by anti-CD44 and anti
      CD49d. The latter is the sequelae of the association between CD44 and CD49d that
      is seen in activated lymphocytes. Significantly, due to CD44-CD49d complex
      formation, CD44 gains access to focal adhesion kinase and CD49d gains access to
      CD44-associated lck and ezrin, such that downstream kinases become activated via
      CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually
      avail themselves of the partner's signaling pathways and the ligand binding of
      each one triggers signaling pathways of both. This strongly influences the
      lymphocytes' activation state and function.

PMID- 17039569
TI  - Spontaneous class switching and B cell hyperactivity increase autoimmunity
      against intracellular self antigen in Lyn-deficient mice.
AB  - IgG autoantibodies cause pathology due to their ability to bind self antigens.
      However, the extent to which the initial B cell activation and isotype switching
      is antigen-driven is unclear and it has been widely proposed that intrinsic B
      cell hyperactivity may be a contributing factor. To explore this issue we
      generated mice with B cell hyperactivity secondary to deficiency in the src
      kinase Lyn that also expressed a gene-targeted anti-hen egg lysozyme Ig construct
      (VDJkappa) capable of class switching to all isotypes. The B cell hyperactivity
      caused spontaneous hypersecretion of antibodies and class switching to IgM, IgA,
      IgG1 and IgG3 isotypes in the absence of self antigen, and this persisted as an
      autoimmune phenomenon in the presence of intracellularly expressed hen egg
      lysozyme. Exaggerated class switching was also unaffected by antigen in vitro.
      These findings show that systemic high-avidity intracellular self antigens do not
      induce self tolerance in the face of B cell hyperactivity. Under these
      circumstances, spontaneous activation of hyperactive B cells leads to isotype
      switching and the development of high titres of IgG autoantibodies against
      intracellular proteins.

PMID- 17039570
TI  - Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune
      myocarditis.
AB  - The most common reason for heart failure in young adults is dilated
      cardiomyopathy often resulting from myocarditis. Clinical studies and animal
      models provide evidence that an autoimmune response against heart myosin is the
      underlying reason for the disease. IL-12 has been suggested to play a key role in
      development of experimental autoimmune myocarditis (EAM), as IL-12p40 and IL
      12Rbeta1 knockouts are protected from disease. In this study, we have compared IL
      12p40-/- mice, IL-12p35-/- mice and mice treated with a neutralizing IL-23
      antibody in EAM and found that in fact IL-23, not IL-12, is responsible for
      inflammatory heart disease. However, these cytokines appear to have redundant
      activity for priming and expansion of autoreactive CD4 T cells, as specific T
      cell proliferation was only defective in the absence of both cytokines. IL-23 has
      been suggested to promote a pathogenic IL-17-producing T cell population. We
      targeted IL-17 by capitalizing on an active vaccination approach that effectively
      breaks B cell tolerance. Neutralization of IL-17 reduced myocarditis and heart
      autoantibody responses, suggesting that IL-17 is the critical effector cytokine
      responsible for EAM. Thus, targeting of IL-23 and IL-17 by passive and active
      vaccination strategies holds promise as a therapeutic approach to treat patients
      at risk for development of dilated cardiomyopathy.

PMID- 17039571
TI  - A note on cointegration of health expenditures and income.
AB  - Utilizing a panel data set of 50 US states, this note investigates
      nonstationarity and cointegration of health care expenditures and gross state
      products (GSP). Both the individual state-based method and the recent panel data
      method are applied. Allowing for structural breaks in the test, we find that
      health care expenditures and GSP are both nonstationary. The evidence also
      suggests that the two series form a cointegrating relationship. The income
      elasticities of health spending vary over states and became smaller in the 1990s.

PMID- 17039572
TI  - An empirical analysis of US and Japanese health insurance using age-period-cohort
      decomposition.
AB  - Aggregate data on household health insurance expenditure in the US and Japan that
      are classified by period and age are decomposed into age, period, and cohort
      effects by using the Bayesian cohort models. These models are developed to
      overcome the identification problem involved in cohort analysis. Despite the
      differences between the health insurance systems of the two countries, three
      interesting empirical findings are obtained. First, in both the countries, the
      age effects are the most influential, and the cohort effects have negligible
      influence. The latter provides a striking policy implication since the
      generational imbalance in social security expenditures is widely recognized in
      developed countries. Second, in both the countries, the period effects show a
      roughly upward trend. Finally, the age effects exhibit a roughly upward movement
      for all age groups in the US; however, in Japan, these effects show a downward
      movement for the 55-59 age group due to the changes in the health insurance
      system on retirement.

PMID- 17039573
TI  - Unrelated medical care in life years gained and the cost utility of primary
      prevention: in search of a 'perfect' cost-utility ratio.
AB  - An important subject of debate in cost-utility analysis of health care programmes
      is whether to include costs of unrelated medical care in life years gained. The
      inclusion of such costs is likely to be of consequence in the case of primary
      prevention. This paper presents different strategies regarding the inclusion not
      only of the costs, but also of the health effects of unrelated medical care in
      economic evaluations. Four different cost-utility ratios are presented and
      related to the criterion of internal consistency. In addition, the possibility to
      relate the ratios to a well-posed decision problem is analysed. An example
      computes the different ratios for smoking cessation interventions in different
      age groups. Including health care costs of unrelated medical care in life years
      gained increases cost utility ratios, but excluding unrelated medical costs
      favours smoking cessation interventions targeted at older smokers over those at
      younger smokers. We conclude that for primary prevention only a cost utility
      ratio that includes both the costs and effects of unrelated medical care meets
      the criterion of internal consistency and is related to a meaningful decision
      problem. Therefore, this type of cost-utility ratio should be preferred even if
      the data requirements may be substantial.

PMID- 17039574
TI  - Vinyl polymers as non-viral gene delivery carriers: current status and prospects.
AB  - Since the first application of polymers as non-viral gene delivery systems in
      1965 by Vaheri and Pagano using functionalised dextran (A. Vaheri and J. S.
      Pagano, "Infectious poliovirus RNA: a sensitive method of assay", Virology 1965,
      27, 434-6), a large number of different polymers have been developed, studied and
      compared for application as DNA carriers. Vinyl-based polymers are one type of
      polymers that have gained considerable interest. The interest in developing this
      particular type of polymer is partly related to the straightforward way in which
      large amounts of these polymers can be prepared by radical (co)polymerisation.
      This opens up a path for establishing a wide range of structure-property
      relations using polymer libraries. The present review aims to give an overview of
      past and ongoing research using vinyl-based gene delivery systems. The
      application of cationic, neutral and zwitterionic polymers as DNA carriers is
      summarised and discussed. [structure: see text] Chemical structure of DEAE
      functionalised dextran.

PMID- 17039575
TI  - Measuring cell adhesion on RGD-modified, self-assembled PEG monolayers using the
      quartz crystal microbalance technique.
AB  - In this study, the suitability of a flow-through quartz crystal microbalance
      system for the detection of the adhesion of rMSCs and 3T3-L1 fibroblasts on
      different surfaces is demonstrated. Frequency shifts for rMSCs of -6.7 mHz x
      cell(-1) and -2.0 mHz x cell(-1) for 3T3-L1 cells could be detected on non
      modified gold sensors, revealing that the frequency shift per cell is comparable
      to that of a static setup. Modifying the sensor surface with SAMs of
      thioalkylated omega-amine-terminated PEG derivatives led to cell-adhesion
      resistant surfaces. Total frequency shifts of only -20 +/- 7 Hz showed that
      protein adsorption was also significantly reduced. Attaching 35 pmol x mm(-2) of
      the GRGDS cell adhesion motif to the SAMs induced specific cell adhesion due to
      RGD-integrin interactions; the resonance frequency dropped by 3.4 mHz x cell(-1).
      Furthermore, the kinetics of cell detachment could be determined. The
      corresponding processes were completed after 10 min for trypsin, and not before
      90 min with GRGDS. Moreover, the detectability of cell adhesion was shown to
      increase after the addition of manganese cations. The total decrease in the
      resonance frequency was almost 80 Hz in the presence of Mn(2+) (6.4 mHz x cell(
      1)). [image: see text] Staining the cytoskeleton of the rMSCs shows that the
      GRGDS-modified surfaces are almost completely covered with well-spread cells.

PMID- 17039576
TI  - Rapid and efficient enzyme encapsulation in a dendrimer silica nanocomposite.
AB  - We report the entrapment of horseradish peroxidase and quantitative encapsulation
      of glucose oxidase within silica nanoparticles by utilizing an amine-terminated
      dendritic template. Our improved strategy employs a water-soluble biomimetic
      template which is able to catalyze the condensation of Si(OH)(4) to silica
      nanoparticles while trapping an enzyme inside the mesoporous material. Kinetic
      analysis shows enzyme functionality to be mostly unchanged. Also, the role of pI
      and ionic strength within the encapsulation environment was found to strongly
      influence encapsulation. These results suggest that the electrostatic
      manipulation of a strong supramolecular silica-precipitating complex of enzyme
      and dendrimer has the potential of adding a vast array of chemical and biological
      activity to hybrid materials. [image: see text] Enzyme immobilization within a
      silica nanocomposite.

PMID- 17039577
TI  - Amphiphilic poly(D,L-lactic acid)/poly(ethylene glycol)/poly(D,L-lactic acid)
      nanogels for controlled release of hydrophobic drugs.
AB  - Photocrosslinked nanogels with a hydrophobic core and hydrophilic shell are
      successfully fabricated with the goal of obtaining a biocompatible and
      biodegradable drug carrier for hydrophobic anticancer drugs. These nanogels are
      composed of amphiphilic triblock copolymers, poly(D,L-lactic acid)/poly(ethylene
      glycol)/poly(D,L-lactic acid) (PLA-PEG-PLA), with acrylated groups at the end of
      the PLA segments. The copolymers are synthesized by ring-opening polymerization
      and possess a low CMC (49.6 mg x L(-1)), which easily helps to form micelles by
      self-assembly. The acrylated end groups allow the micelles to be photocrosslinked
      by ultraviolet irradiation, which turn the micelles into nanogels. These nanogels
      exhibit excellent stability as a suspension in aqueous media at ambient
      temperature as compared to the micelles. Moreover, the size of the nanogels is
      easily manipulated in a range of 150 to 250 nm by changing the concentration of
      crosslinkers, e.g., ethylene glycol dimethacrylate, and ultraviolet light
      irradiation time. The nanogels achieve a high encapsulation efficiency and offer
      a steady and long-term release mechanism for the hydrophobic anticancer drug,
      CPT. It shows that these nanogels are useful for a hydrophobic anticancer drug
      carrier system. [pictures: see text] Formation of the PLA-PEG-PLA nanogels.

PMID- 17039578
TI  - Synthesis of fluorinated chitin derivatives via enzymatic polymerization.
AB  - Synthesis of fluorinated chitin derivatives has been achieved using chitinase
      from Bacillus sp. as a catalyst. 6'-Fluoro- (1a), 6-fluoro- (1b) and 6,6'
      difluoro- (1c) chitobiose oxazoline derivatives were newly prepared as TSAS
      monomers for chitinase. Ring-opening polyaddition of these monomers proceeded
      effectively at pH 8.0-9.0 and 30-40 degrees C, giving rise to alternatingly 6
      fluorinated chitin derivatives (2a and 2b) from 1a and 1b, and fully 6
      fluorinated chitin derivative (2c) from 1c under total control of
      regioselectivity and stereochemistry. XRD measurements revealed that
      polysaccharides 2a and 2b had crystalline structures similar to that of alpha
      chitin. [reaction: see text]

PMID- 17039579
TI  - Application of liquid chromatography/quadrupole time-of-flight mass spectrometry
      (LC-QqTOF-MS) in the environmental analysis.
AB  - This paper gives an overview of the potentials of liquid chromatography-hybrid
      quadrupole time-of-flight mass spectrometry (LC-QqTOF) in the environmental
      analysis. Examples of applications of QqTOF instruments for target analysis of
      pharmaceuticals and pesticides are presented and discussed, as well as
      applications aimed on the identification of unknown compounds present in
      environmental waters or on the elucidation of structures of biodegradation and
      photodegradation products. Specific issues such as uncertainty of mass
      measurement and quantitative performances are discussed in details.

PMID- 17039581
TI  - Towards the control and inhibition of glycation-the role of the guanidine
      reaction center with aldehydic and diketonic dicarbonyls. A mass spectrometry
      study.
AB  - Glycation of proteins by glucose and formation of end-stage adducts (AGEs,
      advanced glycation end products) has been implicated in pathological mechanisms
      associated with diabetic complications, macrovascular disease, chronic and renal
      insufficiency, Alzheimer's disease, and aging. Of the carbonyl containing
      compounds involved in this process, alpha-dicarbonyls have particular importance,
      being established as direct intermediates in the formation of well-known AGEs.
      The guanidino group, present in arginine residues, suffers direct modifications
      by sugars and its derivatives, and is considered to be an important chemical
      basis, targeting the control and inhibition of glycation. Seven dicarbonyl
      compounds, aldehydic and diketonic, were reacted with guanidine, in an attempt to
      establish structure/activity relationships. Electrospray mass spectrometry,
      together with tandem mass spectrometry, was used to identify and characterize the
      reaction products. The reactivity of guanidine was found to vary with the
      dicarbonyls used. For glyoxal, a high amount of dihydroxyimidazolidine was
      formed, whereas for methylglyoxal, dihydroxyimidazolidine was slowly converted
      into hydroimidazolone. Interestingly, aqueous guanidine was found to prevent
      argpyrimidine formation. The formation of several amine-dicarbonyl moieties was
      observed for the larger alkyl-diketonic dicarbonyls reaction systems, in
      particular. Molecular structures, bearing a polar chain, of an imidazole ring,
      and a nonpolar one, of alkyl groups, located at both sides of the imidazole
      rings, were attributed to these moieties. Gas-phase experiments suggested that
      the larger alkyl groups have a preference for being located at one of the sides
      of the imidazole rings. Moreover, the referred amine-dicarbonyl moieties are
      formed via (dihydroxyimidazolidine - 2H2O) moieties. The latter
      (dihydroxyimidazolidine - 2H2O) moieties are formed in high amounts in the larger
      alkyl-diketonic dicarbonyl reactions. Since these moieties react with dicarbonyl
      molecules, and react even faster with already modified amine functions, we can
      foresee that these species may be useful for controlling and inhibiting glycation
      of larger biomolecules, such as proteins.

PMID- 17039582
TI  - Coming home.

PMID- 17039583
TI  - CR2/346--A baby with stridor.

PMID- 17039584
TI  - CR4/112--Congenital isolated tracheal stenosis with organoaxial gastric volvulus.

PMID- 17039585
TI  - CR6/30--A rare case of cyanosis in a child: almost a misleading diagnosis.

PMID- 17039586
TI  - CR7/102--Left colonic perforation as the initial presentation of CF disease in
      the neonatal period.

PMID- 17039587
TI  - CR9/344--Case of disseminated BCG infection.

PMID- 17039588
TI  - CR11/223--Imaging of obstructive sleep-apnea: report of a case.

PMID- 17039589
TI  - [A rice resistant to the floods].

PMID- 17039590
TI  - CD4 count most cost-effective.

PMID- 17039591
TI  - More focus on prevention and research.

PMID- 17039592
TI  - Gates talks about uncomfortable leaders.

PMID- 17039594
TI  - [Poison control center at the H:S Bispebjerg Hospital open for the public].

PMID- 17039593
TI  - Present and future approaches to Parkinson disease: from molecular insights to
      new therapeutic avenues.

PMID- 17039595
TI  - [Wrong citation--correction and a comment].

PMID- 17039596
TI  - [No comments].

PMID- 17039597
TI  - [Antihypertensive agents and apoplexy].

PMID- 17039598
TI  - [Acupuncture therapy of low back pain 2].

PMID- 17039599
TI  - [Frequencies use facilitates the interpretation of diagnostic results].

PMID- 17039600
TI  - [Press, ethics and genetic screening].

PMID- 17039601
TI  - Warning about postgrooming furunculosis.

PMID- 17039604
TI  - Comparison does not compute.

PMID- 17039602
TI  - A group M consensus envelope glycoprotein induces antibodies that neutralize
      subsets of subtype B and C HIV-1 primary viruses.
AB  - HIV-1 subtype C is the most common HIV-1 group M subtype in Africa and many parts
      of Asia. However, to date HIV-1 vaccine candidate immunogens have not induced
      potent and broadly neutralizing antibodies against subtype C primary isolates. We
      have used a centralized gene strategy to address HIV-1 diversity and generated a
      group M consensus envelope gene with shortened consensus variable loops (CON-S)
      for comparative studies with wild-type (WT) Env immunogens. Our results indicate
      that the consensus HIV-1 group M CON-S Env elicited cross-subtype neutralizing
      antibodies of similar or greater breadth and titer than the WT Envs tested,
      indicating the utility of a centralized gene strategy. Our study also shows the
      feasibility of iterative improvements in Env immunogenicity by rational design of
      centralized genes.

PMID- 17039605
TI  - Patient care. You look marvelous.

PMID- 17039603
TI  - Attacks on amalgam raise moral, ethical questions.

PMID- 17039606
TI  - Technology. The bidding begins.

PMID- 17039607
TI  - [Physicians and scientific research: slight decline of the numbers of physicians
      with a doctoral degree].

PMID- 17039609
TI  - Alternative milks not suitable for allergic children.

PMID- 17039608
TI  - 'Special' plans for CMS. HHS to keep tabs on physician-owned hospitals.

PMID- 17039610
TI  - Sources that support the fluoridation of community water supplies is indeed
      impressive.

PMID- 17039611
TI  - Oral pathology quiz #52. Case numner 2. Vascular leiomyoma.

PMID- 17039612
TI  - Oral pathology quiz #52. Case number 3. Ameloblastoma.

PMID- 17039613
TI  - Oral pathology quiz #52. Case number 4. Odontogenic myxoma.

PMID- 17039614
TI  - Illinois steps into HRDI probe. Attorney general issues subpoenas regarding think
      tank.

PMID- 17039615
TI  - Weight lifting in the human brain.

PMID- 17039616
TI  - Taking on P4P, gain-sharing.

PMID- 17039617
TI  - Recurrent worries. When anxieties interfere with life.

PMID- 17039618
TI  - Pandemic flu. What you need to know.

PMID- 17039619
TI  - Healthy eating. One-pot meals. A way to welcome fall.

PMID- 17039620
TI  - A good night's sleep. Sleep loss can affect not only your quality of life, but
      your health as well.

PMID- 17039622
TI  - Who'll watch the kids? Even the most devoted parents need time away from their
      children. Here the experts help you find a sitter you can trust.

PMID- 17039621
TI  - Peak performance.
AB  - Earlier this year, a Pittsburgh-based adventurer became the first American with
      diabetes to reach the top of Mount Everest. He proved that nothing--not record
      breaking winds, freezing temperatures, dangerous ice, or his disease--would slow
      him down.

PMID- 17039623
TI  - Autumn harvest. Whether sliced, roasted, or pureed, fall vegetables offer many
      ways to welcome in this beautiful season.

PMID- 17039624
TI  - Outbreak news. Acute watery diarrhoeal syndrome, Ethiopia.

PMID- 17039625
TI  - Outbreak news. Botulism, Canada and United States.

PMID- 17039626
TI  - Recommended composition of influenza virus vaccines for use in the 2007 influenza
      season.

PMID- 17039627
TI  - Paradoxes of abortion and prenatal injury.

PMID- 17039628
TI  - The reversal test: eliminating status quo bias in applied ethics.

PMID- 17039629
TI  - Bone void filler in posterior iliac crest reconstruction and to supplement
      intertransverse process fusion.

PMID- 17039630
TI  - Gender and ethics committees: where's the 'different voice'?
AB  - Prominent international and national ethics commissions such as the UNESCO
      International Bioethics Committee rarely achieve anything remotely resembling
      gender equality, although local research and ethics committees are somewhat more
      egalitarian. Under-representation of women is particularly troubling when the
      subject matter of modern bioethics so disproportionately concerns women's bodies,
      and when such committees claim to derive 'universal' standards. Are women missing
      from many ethics committees because of relatively straightforward, if
      discriminatory, demographic factors? Or are the methods of analysis and styles of
      ethics to which these bodies are committed somehow 'anti-female'? It has been
      argued, for example, that there is a 'different voice' in ethical reasoning, not
      confined to women but more representative of female experience. Similarly, some
      feminist writers, such as Evelyn Fox Keller and Donna Haraway, have asked
      difficult epistemological questions about the dominant 'masculine paradigm' in
      science. Perhaps the dominant paradigm in ethics committee deliberation is
      similarly gendered? This article provides a preliminary survey of women's
      representation on ethics committees in eastern and western Europe, a critical
      analysis of the supposed 'masculinism' of the principlist approach, and a case
      example in which a 'different voice' did indeed make a difference.

PMID- 17039631
TI  - Safety, identity and consent: a limited defense of reproductive human cloning.
AB  - Some opponents of reproductive human cloning have argued that, because of its
      experimental nature, any attempt to create a child by way of cloning would risk
      serious birth defects or genetic abnormalities and would therefore be immoral.
      Some versions of this argument appeal to the consent of the person to be
      conceived in this way. In particular, they assume that if an experimental
      reproductive technology has not yet been shown to be safe, then, before we use
      it, we are morally obligated to get either the actual consent or the presumed
      consent of the person to be conceived. In this article, I attempt to explain the
      appeal of such consent-based arguments as deriving from a mistaken view of
      personal identity. I then argue that since this view is false, such arguments are
      unsound. Finally, I argue that even if reproductive cloning is unsafe, it may
      still be morally permissible in some circumstances.

PMID- 17039632
TI  - Moral considerations in body donation for scientific research: a unique look at
      the University of Tennessee's anthropological research facility.
AB  - This paper discusses keys to the moral procurement, treatment and disposition of
      remains used for scientific research, specifically those donated to the
      University of Tennessee's Anthropological Research Facility (ARF). The ARF is an
      outdoor laboratory dedicated to better understanding the fate of human remains in
      forensic contexts, and focuses its research on decomposition, time since death
      estimates, body location and recovery techniques, and skeletal analysis.
      Historically, many donations were unclaimed bodies received from medical
      examiners (although it will be shown that this trend is changing), and it has
      been argued that the use of the unclaimed bodies for medical or scientific
      purposes is a violation of autonomy since no consent was given by the individual.
      It is argued here, however, that the domain of autonomous choice extends to one's
      own corpse only insofar as expressed wishes are made known prior to one's death,
      and that in the absence of expressed intent toward final disposition, it is
      acceptable for institutions to receive donations from medical examiners or family
      members. This paper also discusses other philosophical issues related to
      donation, consent and autonomy, and the forensic benefits of research conducted
      at the Anthropological Research Facility.

PMID- 17039633
TI  - Speeding up cancer-drug development.

PMID- 17039634
TI  - Appraisal of bevacizumab and cetuximab for treatment of metastatic colorectal
      cancer in the UK.

PMID- 17039635
TI  - When DNA means 'do not attempt'.

PMID- 17039637
TI  - Eyeglasses: score spectacular savings.

PMID- 17039636
TI  - Bagged salads: the yuck factor.

PMID- 17039638
TI  - Generic drugs: shop around for the best deals.

PMID- 17039640
TI  - Acupuncture was better than no acupuncture but did not differ from minimal (sham)
      acupuncture for chronic low back pain at 8 weeks.

PMID- 17039639
TI  - Evaluation of studies of treatment harm.

PMID- 17039641
TI  - Medicare physician payments and spending.
AB  - The Medicare program's physician payment method is intended to control spending
      while ensuring beneficiary access to physician services, but there are signs that
      it may not be working. The physician's role in the health care delivery system as
      the primary source of information and treatment options, together with growing
      demand for services and the imperfect state of knowledge about appropriate
      service use, challenge Medicare's ability to achieve these two goals. This issue
      brief describes the history of physician spending and the contribution of
      escalating service use and intensity of services to the rise in Medicare outlays,
      setting the stage for further discussion about the use of the Medicare payment
      system to control spending and ensure access.

PMID- 17039642
TI  - [Acute cerebral symptoms in elderly women].

PMID- 17039643
TI  - [All cases of stroke has a cause].

PMID- 17039644
TI  - A real head scratcher. Schools are struggling with how best to handle lice.

PMID- 17039645
TI  - Vanished behind the counter. Starting this week, you'll need help buying your
      claritin and nyquil.

PMID- 17039646
TI  - Behind the baby count.

PMID- 17039647
TI  - Taste comparison of corticosteroid suspensions.
AB  - OBJECTIVE: Although numerous taste studies have compared the palatability of
      antibiotic suspensions, few have compared the palatability of corticosteroid
      suspensions. Therefore, we compared the taste of 8 commonly prescribed liquid
      corticosteroid suspensions with the intent to help guide prescribing practices
      and improve patient compliance. METHODS: We conducted a randomized, double-blind
      study using 31 adult volunteers ages 24 to 57. All volunteers were asked to
      sample 8 different pediatric corticosteroid suspensions and to rate the
      palatability of their taste and aftertaste. The mean scores for each sample were
      then compared. RESULTS: The 8 suspensions fell into 2 groups based on their taste
      scores: one group with relatively high scores or more acceptable tastes (Orapred,
      Pediapred, and a dexamethasone suspension) and a second group with relatively low
      scores or less acceptable tastes (a prednisone suspension and 4 cherry-flavored
      prednisolone suspensions). CONCLUSIONS: The results demonstrate a significant
      difference in palatability between corticosteroid suspensions. Not only will this
      new information help clinicians choose between otherwise equivalent
      corticosteroid suspensions but, given the importance children place on taste, may
      improve compliance as well.

PMID- 17039648
TI  - Successful treatment of hand and foot psoriasis with efalizumab therapy.
AB  - Hand and foot psoriasis can appear in a plaque-type or pustular-type form. Any
      form of psoriasis that occurs on the hands and feet can have a debilitating
      effect on the patient's daily functions. Here we present a case series of
      patients with plaqueor pustular-type hand and foot psoriasis whose conditions
      were successfully managed with the biologic agent efalizumab. In many of these
      patients, the disease was refractory to multiple systemic psoriasis treatments.
      Treatment with efalizumab was effective and well-tolerated, with few adverse
      events. Many of the patients described here reported an improvement in both their
      physical functioning and health-related quality of life. The efficacy of
      efalizumab in treating these cases of hand and foot psoriasis suggests that it
      may provide therapeutic benefit.

PMID- 17039649
TI  - Hereditary angioedema.
AB  - Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by a C1
      inhibitor deficiency. It is characterized by potentially life-threatening
      recurrent episodes of angioedema of the skin and mucosa. Several recent studies
      have further elucidated the immunology of HAE implicating bradykinin, the key
      mediator of the contact system. This article reviews the pathophysiology,
      subtypes, and clinical features of HAE. Therapeutic approaches for various
      clinical situations (emergency and prophylactic regimens) are also discussed.

PMID- 17039650
TI  - Topical diphenylcyclopropenone as a measure of immune competence in HIV
      seropositive subjects.
AB  - BACKGROUND: CD4 T cell counts are recognized as the standard method for
      monitoring HIV-seropositive patients and, along with viral load, are clinically
      important as indicators for initiating highly active antiretrovival therapy
      (HAART). Skin reaction scores following topical application of
      diphenylcyclopropenone (DPC) also demonstrate diagnostic utility as a functional
      measure of immune competence. METHODS: We used low sensitizing doses of DPC in 40
      patients applied in a non-volatile, non-irritating topical delivery system to
      assess immune competence in 40 HIV-seropositive subjects with a range of CD4 T
      cell counts. Standardized patch test reading scores were used, with 2+ or greater
      scores (erythema and induration) indicative of a positive response. The patch
      test scores were then compared with CD4 counts. RESULTS: Application of DPC in
      concentrations of 0.4% and 0.2% successfully resulted in 90% sensitivity skin
      reaction scores in subjects with >300 CD4 T cells/microL, following a single 0.1
      mL application to the inner aspect of the arm. Lower DPC concentrations of 0.1%
      and 0.05% were too low for initial sensitization reactions. Three subjects with
      CD4 counts between 150 and 300 cells/microL showed positive skin reactions
      indicating that this DPC test gives the clinician information on cellular
      immunity beyond the CD4 count. CONCLUSION: We conclude that a single topical
      application of DPC at concentrations between 0.2% and 0.4% can serve as a measure
      of immune competence in HIV-seropositive patients. As a functional measure of
      immunocompetence, this DPC test provides information beyond a CD4 count, which is
      particularly relevant to HIV-positive subjects with CD4 counts between 200 and
      350 cells/microL.

PMID- 17039651
TI  - A novel vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia.
AB  - Varicella-zoster virus is the causal agent of varicella and herpes zoster in
      humans. Herpes zoster results from reactivation of latent varicella-zoster virus
      (VZV) within the sensory ganglia. The incidence and severity of herpes zoster
      increase with advancing age. More than half of all persons in whom herpes zoster
      develops are older than 60 years. The most frequent debilitating complication is
      postherpetic neuralgia, a neuropathic pain syndrome that persists or develops
      after the dermatomal rash has healed and can be prolonged and disabling. There
      are many limitations of current therapies for herpes zoster and postherpetic
      neuralgia. A live attenuated VZV vaccine has been developed and recently approved
      by the FDA for the prevention of herpes zoster in individuals 60 years of age and
      older. In a randomized, double-blind, placebo-controlled trial with 38,546
      patients 60 years of age or older, the use of the zoster vaccine reduced the
      burden of illness due to herpes zoster by 61.1% (P < .001), reduced the incidence
      of postherpetic neuralgia by 66.5% (P < .001), and reduced the incidence of
      herpes zoster by 51.3% (P < .001). In this review, we will discuss the history of
      the use of the varicella vaccine in children, and the subsequent development of
      the new zoster vaccine.

PMID- 17039652
TI  - Inhibition of propionibacterium acnes by bacteriocin-like inhibitory substances
      (BLIS) produced by Streptococcus salivarius.
AB  - We report the in vitro inhibition of Propionibacterium acnes (P. acnes) by a
      bacteriocin-like inhibitory substance (BLIS-like substance) produced by
      Streptococcus salivarius (S. salivarius). Bacteriocins are proteinaceous
      substances produced by bacteria that are capable of inhibiting the growth of
      similar bacterial strains. Unlike classical antibiotics, they have a relatively
      narrow spectrum of killing activity, resulting in a reduction in the intensity of
      selection for resistance. These findings suggest that BLIS may potentially be
      used for its anti-P. acnes activity in the treatment of acne.

PMID- 17039653
TI  - A protocol for facial volume restoration with poly-L-lactic acid.
AB  - Poly-L-lactic acid is a biodegradable synthetic polymer used in an injectable
      form for subcutaneous volume restoration. Volumetric correction following
      subcutaneous and deep dermal injection of poly-L-lactic acid is thought to occur
      through a foreign body tissue response leading to increased production of
      fibroblasts and subsequent neocollagenesis. Despite the growing popularity and
      use of this material, there has been a scarcity of published information
      describing proper injection technique, and many practitioners remain unfamiliar
      with its use. Appropriate injection technique is critical since incorrect
      placement of the material can lead to long-lasting unintended results. We present
      a protocol for successful injection of poly-L-lactic acid into the submalar and
      buccal regions.

PMID- 17039654
TI  - Oral isotretinoin for acne, adjusting treatment according to patient's response.
AB  - BACKGROUND: Oral isotretinoin is an established effective therapy for acne. No
      published data is available on the efficacy and side effects of this drug in
      Iranian patients. PATIENTS AND METHODS: A total of 132 acne patients with a mean
      age of 22.9 +/- 6.2 years were treated with oral isotretinoin (Roaccutane) and
      followed-up from 1999 through 2005. Each patient was started with a dose of 0.75
      mg/kg per day until all active lesions healed, followed by a maintenance dose of
      20 mg/kg per day for one more month. Laboratory tests were done at monthly
      intervals. Evaluation of clinical response was based on Leeds technique. Patients
      were followed-up for a mean period of 4.4 years. RESULTS: Most of the patients
      had severe nodulocystic acne involving both trunk and face. Treatment was
      continued for 6.6 +/- 2.5 months with a cumulative dose of 111.5 mg/kg +/- 33.9.
      The mean final improvement rate was 96.7% (95% CI, 84.9% to 108.5%). There was no
      correlation between improvement rate and age, sex, duration of acne, length of
      treatment, or cumulative dose. Side effects were generally mild and treated
      conservatively. In the follow-up, period 18.35% experienced relapse after a mean
      interval of 1.28 years, 9.17% required a second course of isotretinoin, and only
      one case needed 3 courses of treatment. CONCLUSION: Isotretinoin is an effective
      and safe treatment for acne in Iranian patients. Starting treatment with a high
      dose and modifying the length of treatment based on the therapeutic response in
      each patient, might lead to a rapid and good response rate with minimal side
      effects.

PMID- 17039656
TI  - Induction of lesional and circulating leukocyte apoptosis by infliximab in a
      patient with moderate to severe psoriasis.
AB  - Infliximab demonstrates high efficacy in treating psoriasis in a high proportion
      of patients. In this report we demonstrate induction of plaque (T cells,
      dendritic cells) and peripheral blood (T cells, monocytes) leukocyte apoptosis
      following a single infliximab infusion in a psoriasis patient.

PMID- 17039655
TI  - Comparison of metformin versus rosiglitazone in patients with Acanthosis
      nigricans: a pilot study.
AB  - BACKGROUND: Acanthosis nigricans (AN) is a skin condition commonly present on the
      neck of obese subjects. Obesity is often accompanied by insulin resistance and/or
      hyperinsulinemia. Metformin and rosiglitazone are 2 pharmacologic agents useful
      in conditions characterized by insulin resistance. OBJECTIVE: The aim of our
      study was to compare the efficacy of metformin versus rosiglitazone on AN lesions
      of the neck as well as their effects on metabolic and anthropometric variables.
      METHODS: This 12-week randomized, open-label pilot study involved overweight or
      obese subjects with AN treat with either metformin (n=4) or rosiglitazone (n=3).
      RESULTS: Only the rosiglitazone group showed a significant reduction in insulin
      levels. No effect on the severity of AN was observed, but modest improvements of
      skin texture occurred in both treatment groups. CONCLUSIONS: Metformin and
      rosiglitazone were well-tolerated. Although efficacy on skin lesions was very
      modest, their use in acanthotic subjects might be useful during longer treatment
      periods.

PMID- 17039657
TI  - Etanercept therapy for silicone granuloma.
AB  - A patient developed a typical, painful, and debilitating reaction on the thighs
      following injection of ostensibly medical grade "silicone" to achieve alteration
      of body contours. The refractory silicone granuloma responded dramatically to
      treatment with etanercept.

PMID- 17039658
TI  - An intertrigo-like eruption from pegylated liposomal doxorubicin.
AB  - Pegylated liposomal doxorubicin (PLD) is a chemotherapeutic agent used in the
      treatment of solid tumors. It has a considerably lower risk of cardiotoxicity
      than its parent compound, doxorubicin. PLD also has a different cutaneous side
      effect profile than doxorubicin, and its cutaneous toxicity can be dose limiting.
      We report the case of a 60-year-old woman who developed erythema and erosions in
      the axilla and groin while on PLD for breast cancer. Nystatin was ineffective.
      Biopsies revealed an interface dermatitis with epidermal dysmaturation. Bland
      emollients and reduction in the dose of PLD resulted in resolution of the
      eruption. An intertriginous eruption with histological features of epidermal
      dysmaturation and an interface dermatitis has been previously reported in the
      dermatopathology literature. This eruption appears to be a distinct cutaneous
      toxicity of PLD.

PMID- 17039659
TI  - Etanercept responsive acrodermatitis continua of Hallopeau: is a pattern
      developing?
AB  - Acrodermatitis continua of Hallopeau (ACH) is a rare disease. Little is known
      about its etiology or relative effectiveness of the various therapeutic
      approaches. However, in the literature a pattern seems to be developing on
      successfully treated patients using biologic therapies. Here, we further
      emphasize the potential breakthrough presented by the novel immune based
      therapies. This report consists of a case of etanercept responsive ACH along with
      a brief review of the literature.

PMID- 17039660
TI  - Successful treatment of patch type mycosis fungoides with tacrolimus ointment
      0.1%.
AB  - Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of
      lymphoproliferative disorders caused by clonally-derived, skin-invasive T cells.
      A variety of skin-directed and systemic therapies are available to treat mycosis
      fungoides/Sezary syndrome (MF/SS), the therapeutic choices of which are guided by
      the stage of disease. A 29-year-old man presented at our clinic with pruritic,
      erythematous macules located on the sternum and the lower back. Histological
      findings and immunohistochemistry studies showed patch stage MF. The patient was
      treated with tacrolimus ointment 0.1% twice daily for one month, achieving
      complete remission. Three months after the first episode a relapse was
      successfully treated with the same therapeutic regimen. Tacrolimus is an
      immunomodulatory macrolide that reduces the stimulatory capacity toward T cells
      and is therefore worth investigating as a treatment of CTCL. Topical tacrolimus
      has been related to an unknown effect with the risk for secondary malignancies
      including CTCL. Also, black box warnings have been proposed by the FDA for the
      topical calcineurin inhibitors. Nevertheless, our results in the treatment of
      early stage MF are in agreement with other unpublished data that have observed
      its efficacy. To our knowledge, there is no other case of patch type mycosis
      fungoides treated with tacrolimus ointment 0.1% in the medical literature.

PMID- 17039661
TI  - Wells syndrome: an enigmatic and therapeutically challenging disease.
AB  - Wells syndrome, also known as eosinophilic cellulitis, is an uncommon condition
      whose etiology often remains a mystery. Patients present with recurrent cutaneous
      swellings that are often cellulitic in appearance. Histopathologic evaluation of
      the skin lesions reveals a dense dermal eosinophilic infiltrate, marked edema,
      and characteristic "flame figures". Notably, the picture is devoid of vasculitis.
      Therapy with low-dose systemic steroids has proven variably successful. Clinical
      evidence lending support for the efficacy of other medications has been, for the
      most part, anecdotal. We present a case of Wells syndrome, review the literature,
      and discuss therapeutic options.

PMID- 17039662
TI  - Schools of pharmacology: retinoid update.
AB  - The most widely used retinoids include topical tretinoin (Retin-A), adapalene
      (Differin), topical tazarotene (Tazorac), isotretinoin (Accutane), and acitretin
      (Soriatane). This article will review new uses and developments in tazarotene
      (its failure to secure FDA approval in oral form for psoriasis), adapalene (its
      new 0.3% gel form and use in rosacea), alitretinoin (its use in photoaging),
      bexarotene (its use for psoriasis and chronic hand dermatitis), isotretinoin (the
      IPledge program, its use for neuroblastoma and branded formulation
      pharmacological superiority to generics), and retinoic acid metabolism-blocking
      agents (RAMBAs) (liarazole use for ichthyosis and psoriasis).

PMID- 17039663
TI  - Contact dermatitis: a practice parameter.

PMID- 17039664
TI  - Change in the pattern of IgE reactivity to timothy grass and birch pollen
      allergens over a 20-year period.
AB  - BACKGROUND: Several studies have shown that the prevalence of allergy and
      allergen sensitization has increased in recent years. However, the changes in the
      pattern of IgE reactivity to individual allergens are mostly unknown. OBJECTIVE:
      The aim of this preliminary study was to assess the change in IgE reactivity
      profile to individual timothy grass and/or birch pollen allergens in sera from
      sensitized individuals randomly collected 20 years apart. METHODS: Serum samples
      from 51 sensitized individuals were obtained from 2 cross-sectional surveys
      performed in 1973 and 1994 using random samples from Vammala, Finland. The sera
      were analyzed for IgE reactivity to timothy grass and/or birch pollen extracts,
      recombinant (r)Phl p 1, 2, 5, 6, 7, 11, 12, native (n)Phl p 4, and rBet v 1, 2
      and 4 by immunoassay (ImmunoCAP). RESULTS: The median (range) concentrations of
      IgE antibodies to timothy grass and birch pollen were higher in 1994 than in 1973
      (6.47 [0.35 to >100] kU A/L vs 1.53 [0.40-25.3] kU A/L; P=.0035). The prevalence
      of IgE reactivity to some allergens was higher in 1994 than in 1973, particularly
      rPhl p 5 (52% vs 19%), rPhl p 6 (43% vs 12%), and rBet v 1 (100% vs 29%). There
      was a correlation between timothy grass pollen-specific serum IgE levels and the
      numbers of IgE reactivities to individual allergens (p=0.76, P<.001).
      CONCLUSIONS: The increase in specific IgE levels together with a possible
      increase in the prevalence of IgE reactivity to the major allergens Phl p 5 and
      Bet v 1 between 1973 and 1994 may have contributed to the increase in atopic
      conditions in Finland.

PMID- 17039665
TI  - Variability of Alt a 1 expression by different strains of Alternaria alternata.
AB  - BACKGROUND: While it is well known that there is significant intraspecific
      variation in the content an potency of Alternaria alternata allergens, little
      data has been published on intraspecific variability for individual allergens
      from moulds. OBJECTIVE: To assess the variability of Alt a 1 expression in
      different strains of A alternata. METHODS: Eleven strains of A alternata were
      cultured in a Czapek broth medium and culture filtrate extracts were obtained. A
      sensitive two-site enzyme-linked immunosorbent assay was used to measure Alt a 1
      concentrations in medium following 3 weeks of culture and in culture filtrate
      extracts. RESULTS: Expression of Alt a 1 was highly variable in different strains
      ofA alternata (coefficient of variation > 135%). A good correlation was found
      between Alt a 1 concentrations at the beginning of the process and measurements
      at the end of extract production (r=0.940). CONCLUSIONS: The high variability of
      Alt a 1 expression in different A alternata strains makes it necessary to measure
      Alt a 1 concentrations during the first stage of allergenic extract production in
      order to be able to choose a suitable strain for producing extracts or purifying
      Alt a 1.

PMID- 17039666
TI  - Clinical effects of apple polyphenols on persistent allergic rhinitis: A
      randomized double-blind placebo-controlled parallel arm study.
AB  - BACKGROUND: We often encounter persistent allergic rhinitis due to house dust
      mites in the practice of otolaryngology, and its prevalence in Japan is high
      (18.7%). Persistent allergic rhinitis is usually treated with antihistamines and
      local steroids, but they often cause adverse effects such as sedation and
      drowsiness. Polyphenols derived from apples have been reported to suppress
      histamine release from rat cells, reduce auricular swelling in allergic mice, and
      alleviate skin inflammation in atopic patients. These effects suggest that apple
      polyphenols are effective for the treatment of various allergic disorders, but
      the results of their clinical use have not been reported. OBJECTIVE: To assess
      the effect of drinks containing apple polyphenols on clinical symptoms of
      persistent allergic rhinitis. METHODS: Thirty-three patients aged 15 to 65 years
      with moderate or severe persistent allergic rhinitis in whom the symptoms
      persisted for 3 years or longer were treated without apple polyphenols (control
      group), with a low dose of apple polyphenols, or with a high dose of apple
      polyphenols, and changes in the clinical symptoms were examined. RESULTS:
      Significant improvements were observed in sneezing attacks (P<.05) and nasal
      discharge (P<.01) in the high-dose group and in sneezing attacks (P<.05) in the
      low-dose group. Compared with the control group, an improvement was observed in
      sneezing attacks and nasal discharge in many patients of the polyphenol-treated
      groups. In terms of intranasal findings, a significant improvement was observed
      in swelling of the nasal turbinate in the low-dose group (P<.05). The percentage
      of patients who showed an improvement in swelling of the nasal turbinate was
      higher in the polyphenol-treated groups. CONCLUSIONS: We conclude that apple
      polyphenols are effective in alleviating symptoms of persistent allergic
      rhinitis.

PMID- 17039667
TI  - Prevalence of asthma and allergic diseases in Sanliurfa, Turkey, and the relation
      to environmental and socioeconomic factors: is the hygiene hypothesis enough?
AB  - BACKGROUND: The prevalence of asthma and allergic diseases has been reported to
      be higher in urban than in rural areas between developed and underdeveloped
      countries and within any given country. Studies in Turkey have yielded different
      results for different regions. This study aimed to investigate the prevalence of
      asthma and atopy in Sanliurfa, Turkey, and the influence of environmental
      factors. MATERIALS AND METHODS: We recruited 1108 children from different areas
      of Sanliurfa and administered the questionnaire of the International Study of
      Asthma and Allergies in Childhood. Items asking for socioeconomic data were also
      included. Skin prick and purified protein derivative tests were performed on the
      children. Measles antibodies were determined and feces were analyzed for
      parasites. RESULTS: The total prevalence of atopic diseases was 8.6% (n =
      95/1108), asthma 1.9% (n=21/1108), allergic rhinitis 2.9% (n=32/1108), and
      allergic conjunctivitis 3.8% (n=42/1108). The rate of atopic diseases was 5.6%
      (n=32/573) in children attending schools in peripheral, less urban, slum areas
      while it was 11.8% (n=63/535) in those attending city-center schools (OR, 2.2;
      95% confidence interval [CI]; 1.4-3.5; P<.001). Skin prick test positivity was
      observed in 3.9% (n=43/1108) overall; at schools in slum areas it was 1.9%
      (n=11/573), whereas at central schools the rate was 6% (n=32/535) (OR, 4.08; 95%
      CI, 2.03-8.20; P<.001). The prevalence of asthma and atopic diseases was
      significantly higher in children who have a family history of atopy, attend a
      central school, live in an apartment, have more rooms in their homes, and enjoy
      better economic conditions. CONCLUSION: We found associations between various
      factors suggested by the hygiene hypothesis and asthma, and very low rates of
      prevalence of asthma and atopic diseases both in Sanliurfa in comparison with the
      more developed western regions and in the peripheral slum areas. The hygiene
      hypothesis is helpful in explaining these observations.

PMID- 17039668
TI  - IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in
      cow's milk allergic patients.
AB  - BACKGROUND: Allergic reactions to cow's milk are common in small children. One of
      the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg).
      Reindeer and bovine milk both contain related beta-Lg proteins, but the
      allergenicity of reindeer beta-Lg has not previously been studied. The purpose of
      this study was to analyze the immunological cross-reactivity of IgE antibodies
      from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS:
      Sera from 17 children and a serum pool of 4 patients with elevated cow's milk
      specific IgE were investigated. Beta-Lg from bovine and reindeer milk was
      isolated in native form and an enzyme-linked immunosorbent inhibition assay was
      developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting
      effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS:
      Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg
      varied among patients. In general, reindeer beta-Lg showed significantly lower
      inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine
      beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta
      Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The
      partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests
      that it lacks important bovine epitopes and those that are recognized are only
      weakly bound.

PMID- 17039669
TI  - Changes in the expression of Fas on T lymphocytes after allogeneic fetal thymus
      transplantation in systemic lupus erytematosus mice.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder that can
      produce inflammation in many organ systems. The rate of spontaneous apoptosis in
      lymphocytes from human SLE patients has been reported to be increased both in
      vivo and in vitro. Studies of fetal thymus transplantation in an autoimmune
      syndrome indicate that cellular immunity can be reconstituted and regulatory T
      cell functions can be normalized. OBJECTIVES: The aim of this study was to assess
      changes in Fas expression on T lymphocytes following fetal thymus transplant.
      METHODS: (B/CxB6) F1 (H-2d/h) female F1 mice were assigned to groups designated
      transplantation, normal, and control. Mice in the transplantation and control
      groups received parental BALB/c lymphocytes intravenously. Thirty days after
      injection of the lymphocytes, each F1 mouse in the transplantation group received
      a fetal thymus graft under the right renal capsule. Mice in the control group did
      not receive thymus transplant and mice in the normal group received neither
      parental lymphocytes nor a fetal thymus graft. All mice received cyclosporin A at
      2 mg/kg daily for the first 12 days after transplantation or starting on the
      corresponding day. Thirty days after thymus transplantation, F1 mice were
      sacrificed and expression of Fas in peripheral blood lymphocytes was analyzed by
      flow cytometry. RESULTS: The percentage of CD4Fas+ T lymphocytes was
      significantly increased in the control group and the transplantation group
      compared with the normal group. Corresponding significant differences were
      observed for CD8Fas+, CD4CD25Fas', and CD45RB(low)Fas+ T lymphocytes.
      CONCLUSIONS: In this study, we found that fetal thymus transplantation had a
      significant effect on the expression of Fas by T cell subtypes in SLE mice.

PMID- 17039670
TI  - Tahini, a little known sesame-containing food, as an unexpected cause of severe
      allergic reaction.
AB  - We describe the case of a young woman with asthma and confirmed food allergy to
      sesame who had 2 severe systemic reactions after the inadvertent ingestion of
      tahini, a paste made with ground sesame seeds that is not generally known by
      physicians and patients as a sesame-containing food. A double-blind placebo
      controlled food challenge confirmed the allergy to tahini in our patient. As new
      products and recipes are being introduced from around the world on a regular
      basis, it is essential that at-risk patients are able to obtain information about
      allergens used as ingredients and as potential contaminants. This should be
      applied not only to packaged food but also to freshly made foods, such as those
      served in restaurants.

PMID- 17039671
TI  - Cross-reactivity among amide-type local anesthetics in a case of allergy to
      mepivacaine.
AB  - Among the various adverse reactions to local anesthetics, IgE-mediated reactions,
      particularly to the more commonly used amide group, are extremely rare. We report
      the case of a 39-year-old man who suffered itching and generalized urticaria with
      facial angioedema 15 minutes after administration of mepivacaine. Skin tests
      revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine,
      but negative reactions to bupivacaine and levobupivacaine. Furthermore, double
      blind placebo-controlled subcutaneous challenge with bupivacaine and
      levobupivacaine was well tolerated. We conclude that an extensive allergologic
      study must be carried out in rare cases of true allergic reaction to amide-type
      local anesthetics in order to rule out cross reactivity.

PMID- 17039672
TI  - Human seminal plasma allergy and successful pregnancy.
AB  - Human seminal plasma allergy in women is an uncommon phenomenon. A great variety
      of reactions ranging from local swelling to generalized systemic reactions have
      been described, and local symptoms have often been misdiagnosed as chronic
      vulvovaginitis. Sperm barriers, such as condoms, are the most widely advocated
      method for avoiding these reactions; however this is not acceptable to couples
      who wish to have children. We present a case of a woman with human seminal plasma
      allergy who became pregnant after a fourth cycle of artificial insemination.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblotting showing
      an IgE binding band at 28kDa in the husband's seminal fluid identified the
      culprit allergen. Artificial insemination is an effective way to achieve a
      pregnancy in patients with seminal plasma allergy.

PMID- 17039673
TI  - Meloxicam-associated anaphylactic reaction.
AB  - Anaphylactic reaction to meloxicam has never been reported to date. We report 2
      cases of meloxicam-induced anaphylactic reaction with no sensitivity to another
      selective cyclooxygenase 2 inhibitor. A thorough drug allergy work-up should be
      done before other cyclooxygenase inhibitors are prescribed.

PMID- 17039674
TI  - Drug neosensitization during anticonvulsant hypersensitivity syndrome.
AB  - Anticonvulsant hypersensitivity syndrome (AHS) is a rare, severe drug
      hypersensitivity reaction included in the drug-related rash with eosinophilia and
      systemic symptoms syndrome (DRESS), in which a transient state of immune
      suppression and reactivation of latent virus infections have been observed. We
      describe 5 patients who developed neosensitization to different drugs taken
      during a previous episode of anticonvulsant-related DRESS, in whom skin prick,
      intradermal and/or patch tests were performed to confirm the diagnosis of drug
      hypersensitivity. In 1 patient, transient hypogammaglobulinemia was observed
      during the AHS. Four of the 5 patients developed a delayed skin eruption or a
      delayed systemic hypersensitivity reaction after intake of a drug that they had
      also taken during a previous anticonvulsant DRESS which had occurred months or
      years earlier; in the fifth, a possible reaction was prevented thanks to the
      allergy workup. The diagnosis of drug allergy was demonstrated by positive
      delayed reaction to intradermal test with amoxicillin in 2 cases, positive patch
      tests to paracetamol and amitriptyline in 2 cases, and by clinical evidence of
      ceftriaxone erythroderma in one. The possibility of neosensitization to drugs
      administered during anticonvulsant-related DRESS should be considered. A
      transient state of immunosuppression induced during the anticonvulsant-related
      DRESS may trigger latent virus reactivation and massive nonspecific immune system
      response, which may lead to breakdown of tolerance to other drugs present at that
      time in the organism.

PMID- 17039675
TI  - Diagnosis and management of hypersensitivity reactions caused by oxaliplatin.
AB  - Hypersensitivity reactions to oxaliplatin have been increasing since its
      introduction at the end of the 1990s, but allergy tests with antineoplastic drugs
      are rarely used to aid diagnosis. We describe 5 cases in which hypersensitivity
      reactions to oxaliplatin after several courses of chemotherapy were managed by
      allergy testing and desensitization. Skin prick tests were negative at 1 mg/mL in
      all patients, positive at 10 mg/mL in 2 tested patients, and negative in 10
      control subjects. Intradermal tests were positive and not irritant at 0.01 to
      0.001 mg/mL concentrations. A desensitization protocol with increasing
      concentrations and flow rates was successfully completed in all patients. We
      conclude that prick and intradermal skin tests are useful in the diagnosis of
      hypersensitivity reactions to oxaliplatin and that the desensitization protocol
      performed avoided discontinuation of chemotherapy in all patients.

PMID- 17039676
TI  - Treating sensitivity during tooth whitening.
AB  - The most common side effect of tooth whitening is tooth sensitivity. There are a
      number of materials and techniques for reducing sensitivity. This article focuses
      on potassium nitrate applied either by brushing before initiating whitening or by
      application via a tray during whitening to reduce sensitivity. A detailed step-by
      step procedure for managing hypersensitive patients is described.

PMID- 17039677
TI  - Managing the whitening process.

PMID- 17039678
TI  - Validating the roles of apex locators and sonic instrumentation in root canal
      therapy.
AB  - Paramount to the success of endodontic therapy is determining the working length
      of the canal and, subsequently, effectively cleaning and irrigating the canal.
      Electronic apex locators and sonic instrumentation can help overcome some of the
      clinical and practical challenges inherent in endodontic treatment. This article
      reviews literature findings regarding the applications of apex locators and sonic
      instrumentation to more accurately determine working length and enhance canal
      preparation and irrigation. A clinical technique is presented for completing
      canal preparation and irrigation using sonics.

PMID- 17039679
TI  - Implant therapy using ultraspeed CO2 lasers.
AB  - tial applications are very beneficial clinically. As the technology improves,
      different wavelengths and laser mediums exhibit advantages and disadvantages in
      those clinical applications. The purpose of this article is to discuss the use of
      the CO2 UltraSpeed Laser for implant dentistry as well as how it compares, in the
      author's opinion, to other soft tissue

PMID- 17039680
TI  - The essence of restorative care: long-term tooth preservation.
AB  - Adhesion dentistry and the development of advanced ceramic core materials have
      truly revolutionized the potentials of restorative care. For years, the only
      indirect alternatives were gold and porcelain-fused-to-metal restorations. Today
      we are afforded many choices to customize our treatment. It is the intent of this
      article to review current materials and impose new thought patterns on the
      restorative aspects of vital and nonvital teeth.

PMID- 17039681
TI  - An overview of OSHA training for dentistry.

PMID- 17039682
TI  - OSHA--what is its role in dentistry and how do we provide training?
AB  - The mission of the Occupational Safety and Health Administration (OSHA) is to
      ensure the safety and health of America's workers. Although OSHA's focus is on
      safety, there is a natural overlap into the infection control arena. The work
      practice control, engineering control, and personal protective equipment
      regulations are examples of OSHA safety topics that have a direct impact on
      dental infection control. In a similar fashion, the regulations designed to
      protect the dental health care worker often translate into increased safety for
      the dental patient. To ensure their safety, OSHA requires workers to be
      appropriately trained. This article reviews the regulatory significance of OSHA,
      compares OSHA with other regulatory and advisory agencies, and discusses OSHA's
      training requirements. Principles for conducting training in the dental health
      care setting along with suggestions for assessing training also are presented.

PMID- 17039683
TI  - OSHA safety requirements and the general duty clause.
AB  - Dental offices and clinics are subject to the same general safety requirements as
      other workplaces. Current guidelines, inspections, education, and training focus
      on infectious disease as the major workplace hazard for dental health care
      personnel (DHCP). However, the Occupational Safety and Health Administration has
      cited an increasing variety and number of general safety hazards during
      inspections of dental offices. A review of the general safety requirements for
      personal protective equipment and fire safety as they relate to DHCP follows. The
      authors discuss the responsibility of both employers and employees to perform
      workplace hazard evaluation and to implement education, engineering controls, and
      work practice controls to minimize their exposure to recognized and emerging
      workplace hazards.

PMID- 17039684
TI  - Staying in compliance with the Bloodborne Pathogens Standard.
AB  - Safety and health programs must be annually reviewed and followed. This article
      provides a systematic review of each component of the Bloodborne Pathogens
      Standard and suggestions on how to incorporate the information into staff
      training and routine practice.

PMID- 17039685
TI  - Comprehensive training for hazard communication.
AB  - Long before the Bloodborne Pathogens Standard caught the attention of the dental
      profession, the Occupational Safety and Health Administration required all
      employers to collect information about hazardous chemicals in the workplace and
      provide information and training to employees regarding the materials. The Hazard
      Communication Standard requires employers to establish written programs, collect
      specific information regarding workplace chemicals, and conduct a formal training
      program for employees.

PMID- 17039686
TI  - Interview with Tony Kovner, Ph.D., professor, Wagner Graduate School of Public
      Service, New York University.

PMID- 17039687
TI  - The measurement conundrum.

PMID- 17039689
TI  - Task overlap among primary care team members: an opportunity for system redesign?
AB  - This article presents the results of research on a systematic approach to the
      assignment of primary care work in the Veterans Health Administration. Based on a
      functional job analysis protocol, the study identified overlap in the performance
      of primary care tasks among multiple occupational groups as prima facie evidence
      of opportunities to reallocate work responsibilities. Results show that
      registered nurses, physicians, advanced practitioners, and licensed vocational
      nurses reported performing 60 percent to 97 percent of the same tasks, while
      clerks and health technicians appeared to be underutilized. The frequency and
      duration with which occupational groups performed each task were also examined,
      providing additional evidence to be used in improving clinic efficiency. The
      management of healthcare personnel can be improved through systematic analysis of
      the work, the worker, and the work organization and through more informed
      decisions about the appropriateness of task assignment (or reassignment). This
      article presents an evidence-based approach to personnel management with
      important implications for clinic efficiency. The approach can be used to guide
      strategic planning and staffing decisions by identifying not only who currently
      does the work but, more importantly, who should be doing the work given the full
      array of data.

PMID- 17039688
TI  - Communication and relationship management.

PMID- 17039690
TI  - Managing variation in demand: lessons from the UK National Health Service.
AB  - Managers within the U.S. healthcare system are becoming more aware of the impact
      of variation in demand on healthcare processes. The UK National Health Service
      provides a prime example of a system that has experienced the consequences when
      the issue is not dealt with satisfactorily, having suffered from excessive queues
      for a prolonged period. These delays are mostly caused by a lack of attention to
      variation and inappropriate responses to the queues, rather than a capacity
      shortage. A number of collaborative programs recently have come to grips with
      many of the causes of the queues in both elective care and emergency care.
      Although there are still areas that need large-scale improvement, good progress
      has been made, especially within emergency care. The authors of this article have
      acted as technical advisors to a number of these improvement programs and have
      been able to document many of the practices that have helped to reduce or
      eliminate unnecessary queues and delays across the 200 sites in England that have
      24-hour emergency care facilities. Local program managers at these sites
      continuously reported progress for a period of 18 months. A number of important
      lessons for both the design and control of healthcare processes have emerged from
      the collaborative work. These lessons focus on understanding and measurement of
      demand, capacity planning, reduction of introduced variation, segmentation and
      streaming of work, process design, capacity yield management, and measurement of
      variation.

PMID- 17039691
TI  - The roles of senior management in improving hospital experiences for frail older
      adults.
AB  - With the aging of the population, healthcare executives are paying increased
      attention to fostering safe and high-quality care for older adults who become
      hospitalized. The Hospital Elder Life Program (HELP) is an evidence-based program
      that has been shown to be cost-effective in reducing episodes of delirium,
      functional decline, and long-term nursing home placement for older hospitalized
      adults. Senior administrators are known to play a role in quality improvement,
      but little is known about their roles in adopting clinical improvement programs
      such as HELP. Therefore, we conducted a mixed-methods study of 63 hospitals at
      different stages of adopting HELP to identify key roles and motivations of senior
      management to adopt HELP and the perceived impact of HELP on patient and staff
      outcomes. Our findings can be used by hospital management teams as they identify
      ways to influence and benefit from efforts to improve clinical quality, safety,
      and the experiences of older adults treated in their hospitals.

PMID- 17039692
TI  - Implementation of the EPIC electronic medical record/physician order-entry
      system.

PMID- 17039693
TI  - Pregnancy-related changes in the size of uterine leiomyomas.
AB  - OBJECTIVE: To describe the effects of pregnancy on the growth of leiomyomas using
      sonographic measurements of leiomyomas taken longitudinally during pregnancy.
      STUDY DESIGN: The study population included asymptomatic gravidas with singleton
      pregnancies in whom we identified uterine leiomyomas. We included all women whose
      leiomyomas were measured at least twice during the pregnancy. In a subgroup of
      women we also compared the size of leiomyomas before and after the index
      pregnancy. Using real-time sonography, we measured each leiomyoma in 3 axes and
      averaged the measurements. During subsequent studies we calculated the percent
      change in the size of each tumor. We assessed complications related to the
      presence of these tumors. RESULTS: We evaluated 137 leiomyomas in 72 women
      (average, 2.3 +/- 1.8 per woman). Each underwent an average of 3.7 +/- 2.1 scans.
      The average gestational age at the time of first assessment was 14.4 +/- 5.4
      weeks. The average diameter of the leiomyomas at the first study was 34.2 +/- 23
      mm. On average, there was no significant change in the size of leiomyomas during
      pregnancy. We found that the size, location and our ability to visualize
      leiomyomas varied significantly during pregnancy. Four of the 72 women had
      obstetric complications related to the presence of leiomyomas. CONCLUSION: The
      findings of our longitudinal sonographic assessment of 137 uterine leiomyomas
      suggest that despite the commonly held belief that they tend to enlarge during
      the course of pregnancy, this phenomenon is in fact quite rare.

PMID- 17039694
TI  - First-time births among women 30 years and older in the United States: patterns
      and risk of adverse outcomes.
AB  - OBJECTIVE: To update the trends in initiation of childbirth by age of the mother,
      describing the characteristics of women having their first child at age 30 or
      above, and to determine the risk for adverse pregnancy outcomes for this group of
      women. STUDY DESIGN: This was a cross-sectional study using National Center for
      Health Statistics linked live birth and infant death cohort files from 1995 to
      2000, and Natality file from 1980 to 2002. Analysis was limited to index
      pregnancies only. Logistic regression analysis was used to determine the risk of
      poor outcomes. RESULTS: There is a decreasing trend of first-time births to women
      20-29 years old, while births to women 30 and older are showing a continued rise.
      As compared to 20-29-year-olds, women who start childbearing at age 30 or older
      are at increased risk of maternal complications in general. However, 30-34-year
      olds have a reduced risk for pregnancy-induced hypertension and pre-existing
      hypertension. Infants born to women aged 30 and above are at increased risk for
      prematurity and low birth weight in addition to fetal and infant mortality.
      CONCLUSION: Because of the increasing trend of women starting childbearing in
      their 30s and the increased risk for poor outcomes in older women, health
      providers need to pay extra attention to this group of women as they plan and
      deliver services for them.

PMID- 17039695
TI  - Effectiveness of intraoperative ultrasound in reducing recurrent fibroids during
      laparoscopic myomectomy.
AB  - OBJECTIVE: To detect and study residual fibroids, their recurrence after
      laparoscopic myomectomy (LM) and the risk factors. STUDY DESIGN: A prospective
      analysis (Canadian Task Force classification II-1) was conducted at a university
      affiliated hospital. A total of 42 patients who underwent LM underwent contact
      ultrasonography (CUS) and transvaginal ultrasonography (TVUS) to detect residual
      fibroids. After LM, additional enucleation guided by CUS was performed, and then
      the final residual fibroids were detected using TVUS. The frequency of
      postoperative residual fibroids and their characteristics were evaluated. All
      cases were followed for > 6 months postoperatively to assess recurrence. RESULTS:
      The total number of fibroids enucleated in the initial enucleation was 201, or
      4.8 per patient. Median diameter of the largest fibroids for each patient was 60
      mm. There were 25 additional fibroids enucleated with CUS guidance. Their median
      diameter was 12.1 mm. After the additional enucleation, 33 final residual
      fibroids were identified by TVUS. Their median diameter was 9.0 mm, which was
      significantly smaller than those of the additionally enucleated fibroids (p =
      0.002). The frequency of patients with residual fibroids was calculated in
      relation to the number of enucleated fibroids. The results showed that the
      frequency tended to increase as the number of fibroids increased and that almost
      all the patients (7 of 8 cases, 87.5%) with > or = 10 fibroids had residual ones.
      The median follow-up period was 31 months (range, 6-37), and 8 cases (19.0%) had
      recurrent fibroids. The recurrence rate in patients with > or = 10 fibroids was
      50%. CONCLUSION: Intraoperative CUS was useful in detecting and enucleating
      residualfibroids. As the number of enucleated fibroids increased, the risk of
      residual fibroids and recurrence tended to increase.

PMID- 17039696
TI  - Impact of abnormal results of outpatient fetal heart rate monitoring on maternal
      intervention in labor.
AB  - OBJECTIVE: To conduct a retrospective, cohort study to determine the impact of
      abnormal outpatient fetal heart rate (FHR) testing on maternal interventions in
      labor, including labor induction, operative vaginal delivery and unplanned
      cesarean section. STUDY DESIGN: Our cohort consisted of 1,386 women with
      singleton gestations who had outpatient fetal nonstress testing within 1 week
      prior to giving birth etween 1993 and 1998. Antepartum FHR records were
      interpreted as reassuring or nonreassuring, and pregnancy records were abstracted
      for background medical information, labor interventions and pregnancy outcomes.
      Logistic regression models were used to describe the association between abnormal
      outpatient monitoring results and maternal interventions in labor. RESULTS: After
      adjusting for potential confounders (maternal age, race, prior history of
      cesarean section, antepartum indications for monitoring, fetal presentation and
      abnormal fetal heart rate patterns in labor), women with nonreassuring monitoring
      were 90% more likely to undergo induction. The 2 groups were similar in operative
      vaginal delivery rates, but pregnancies with nonreassuring testing were more than
      twice as likely to end with an unplanned cesarean section. CONCLUSION: Abnormal
      outpatient antenatal FHR testing may be independently associated with an
      increased risk of unplanned cesarean section.

PMID- 17039697
TI  - Mechanisms of twinning: VIII. Maternal height, insulinlike growth factor and
      twinning rate.
AB  - OBJECTIVE: To evaluate the relationship of maternal height to the rate of
      twinning and the possible connection of these parameters to the coexistent level
      of insulinlike growth factor (IGF). STUDY DESIGN: Since spontaneous multiple
      gestations in humans are relatively uncommon in general, it is reasonable to
      consider distin guishing physical attributes such as height, that may have some
      functional relationship to this phenomenon. In a prior study, hereditary and
      dietary factors affecting the level of IGF were found to correlate with the rate
      of twinning. In that height is known to parallel the serum level of IGF, a survey
      of women who had previously conceived spontaneously and had given birth to twins
      or triplets was undertaken. Their heights were compared with the mean value for
      the general female population, RESULTS: Mothers of 129 sets of spontaneous
      multiples displayed a mean height of 164.8 cm as compared to 161.8 cm for the
      general population of women (p < 0.005). CONCLUSION: These data confirm those
      from previous studies and corroborate the proposed relationship between maternal
      height and the rate of twinning. Thus, the results reported here further support
      the IGF model of twinning.

PMID- 17039698
TI  - Prenatally diagnosed balanced chromosome rearrangements: eight years' experience.
AB  - OBJECTIVE: To investigate the incidence and pregnancy outcome of prenatally
      diagnosed balanced chromosome rearrangements from amniocentesis. STUDY DESIGN:
      Between January 1996 and December 2003, we collected cases with balanced
      chromosome rearrangements from amniocentesis specimens submitted to our
      cytogenetics laboratory for fetal karyotyping. Data on maternal age, indication
      for amniocentesis, detailed anatomic sonographic findings, gestational age at
      delivery, newborn birth weight and infant anomalies, if any, were obtained by
      chart review. RESULTS: A total of 66 cases of balanced chromosomal translocations
      or inversions were identified from the 12,468 amniocentesis specimens.
      Specifically, 0.256% had a reciprocal translocation, 0.080% had a Robertsonian
      translocation, and 0.192% had an inversion. The incidences of de novo reciprocal
      translocations, Robertsonian translocations and inversions were 0.080%, 0.016%
      and 0.024%, respectively. Abnormal prenatal sonographic findings occurred in 2
      cases, 1 in an inherited case and 1 in a de novo case. Abnormal postnatal
      findings occurred in 5 cases, 3 in inherited cases and 2 in de novo cases.
      Excluding the cases with minor congenital anomalies, the major congenital anomaly
      rates of inherited and de novo chromosome rearrangements were 1.96% and 6.66%,
      respectively. CONCLUSION: The incidences of prenatally diagnosed de novo
      reciprocal translocations, de novo Robertsonian translocations and de novo
      inversions were higher than those reported in previous, larger series. The major
      congenital anomaly rates for inherited and de novo chromosome rearrangements were
      higher than the 1.4% congenital anomaly rate in our general population.
      Consequently, detailed ultrasound examination and parental karyotyping should be
      viewed as essential measures in dealing with prenatally diagnosed balanced
      chromosome rearrangements.

PMID- 17039699
TI  - Relationship between meconium staining, umbilical cord plasma motilin level and
      infantile colic.
AB  - OBJECTIVE: To assess the effects of meconium-stained amniotic fluid and umbilical
      cord plasma motilin levels on the development of infantile colic. STUDY DESIGN:
      One hundred forty pregnant women referred to our department for labor care were
      enrolled in the study. All subjects were laboring women with singleton, vertex
      presenting fetuses, with a gestational age of > or = 36 weeks. After each infant
      with meconium-stained amniotic fluid was born, the following 2 infants without
      meconium were selected as controls. Umbilical cord plasma motilin levels were
      measured in 47 infants with meconium-stained amniotic fluid and 93 infants with
      no meconium. At the end of the third month of the infants' lives, the development
      of infantile colic was evaluated. Umbilical cord serum specimens were collected
      from 45 infants with colic and 95 infants without colic. Statistics included
      Student's t, chi2 and Mann-Whitney U tests, as appropriate. Multivariate analysis
      was performed. RESULTS: There was no correlation between the presence of meconium
      stained amniotic fluid and the development of infantile colic. No association was
      found between umbilical cord plasma motilin levels and the development of
      infantile colic. Neonatal intensive care unit admission was found to be a
      significant risk factor for the development of infantile colic. CONCLUSION:
      Meconium-stained amniotic fluid and umbilical cord plasma motilin levels do not
      affect the development of infantile colic.

PMID- 17039700
TI  - Alternate evaluations of proteinuria in the gravid hypertensive patient.
AB  - OBJECTIVE: To determine if the 12-hour urine total protein value correlates with
      the 24-hour value and to evaluate the random protein:creatinine ratio as a
      predictor of significant proteinuria (> or = 300 mg/24 h) for use in diagnosing
      preeclampsia. STUDY DESIGN: The study population included 15 patients with
      hypertensive disorders of pregnancy. The patients' urine was collected over 24
      hours in 2 12-hour aliquots. The urine volume, total protein and creatinine were
      measured. The patients' initial voids were collected and evaluated for random
      urine protein and creatinine and calculation of the protein:creatinine ratio. The
      protein:creatinine ratio and 12-hour results were compared to the 24-hour results
      using simple regression analysis. RESULTS: Of the 15 patients, 6 had no
      proteinuria, 5 had mild proteinuria, and 4 had severe proteinuria (60% with
      significant proteinuria). The 12-hour protein results correlated with the 24-hour
      results for patients with mild disease (p = 0.00007, first 12 hours, and p =
      0.012, second 12 hours) and severe disease (p = 0.014 and p = 0.007). The results
      for no disease were mixed: for the first 12 hours there was a poor correlation,
      but the results for the second 12 hours correlated well. The protein:creatinine
      ratio had a significant correlation (p = 0.02), using a cutoff of 0.15, returned
      specificity of 50%, sensitivity of 100%, positive predictive value of 75% and
      negative predictive value of 100%. CONCLUSION: Total protein values for 12- and
      24-hour urine samples correlate well for the diagnosis of preeclampsia. A
      protein:creatinine ratio of < or = 0.15 rules out significant proteinuria. In
      combination, these 2 tests may allow more rapid diagnosis of preeclampsia.

PMID- 17039702
TI  - Pregnancy in a woman with a continent appendicovesicostomy: a case report.
AB  - BACKGROUND: Few cases of pregnancy following the Mitrofanoff procedure (continent
      appendicovesicostomy) have been reported, but in those cases there was an
      increased rate of cesarean delivery with no long-term consequences to renal
      function or to the urinary diversion. CASE: A 15-year-old primagravida with a
      prior nephrectomy for a dysplastic kidney and prior continent
      appendicovesicostomy for urinary retention due to spina bifida occulta and
      neurogenic bladder had a pregnancy complicated by preterm premature rupture of
      membranes, preterm labor, breech presentation and cesarean delivery with the
      assistance of a urologist. The patient had a minimal decline in renal function,
      and she and the infant did well. CONCLUSION: Cesarean delivery should be reserved
      for obstetric indications. Surgical assistance by a urologist at the time of
      cesarean delivery may be helpful.

PMID- 17039701
TI  - Pulmonary benign metastasizing leiomyoma: a report of 2 cases with different
      outcomes.
AB  - BACKGROUND: Benign metastasizing leiomyoma (BML) of the lung is a rare
      manifestation of metastasis from a uterine myoma, in which its benign
      characteristics are maintained. The majority of cases are asymptomatic. CASES:
      Case 1 responded to the classic treatment of oophorectomy, after which an
      improvement in symptoms was achieved. In case 2, however, symptoms appeared
      following oophorectomy and were treated with raloxifene. CONCLUSION: These cases
      show the uncertainty that exists with respect to the evolution and treatment of
      symptomatic BML. Raloxifene is a therapeutic agent that has not been widely
      studied for this purpose but should be considered for inclusion in the arsenal of
      therapeutic options available.

PMID- 17039703
TI  - Spontaneous rupture of uterine surface varicose veins in pregnancy: a case
      report.
AB  - BACKGROUND: Spontaneous rupture of uterine surface varicose veins is rare but may
      become a serious complication of pregnancy. CASE: A 40-year-old woman, gravida 2,
      para 0-0-1-0, presented with worsening generalized abdominal pain after
      occasional nausea, vomiting and diarrhea over the previous 2 days. After a 4-hour
      observation period, sudden onset of severe, prolonged fetal heart rate
      decelerations was recognized along with frequent uterine contractions. Emergency
      cesarean section was performed under a tentative diagnosis of placental
      abruption. A live, female infant weighing 1,730 g was delivered and had Apgar
      scores of 5 and 9 at 1 and 5 minutes, respectively. Intraoperatively,
      approximately 500 mL of hemoperitoneum was present, and multiple bleeding sites
      from varicose veins on the posterior uterine surface were detected. Because the
      maternal vital signs became unstable and hemostasis was difficult, hysterectomy
      was performed and blood transfusion administered. CONCLUSION: Although very rare,
      hemoperitoneum should be included in the differential diagnosis when a pregnant
      woman experiences acute-onset, severe abdominal pain, even without an episode of
      abdominal trauma.

PMID- 17039704
TI  - Arrhythmogenic right ventricular dysplasia in pregnancy: a case report.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by
      progressive fibrous or fibrofatty tissue replacement of the right ventricular
      myocardium. Interspersed adipocytes and fibrous tissue may provide foci for
      arrhythmias. The clinical spectrum of ARVD may include asymptomatic premature
      ventricular complexes to ventricular tachycardia and sudden death. There is
      currently little information about ARVD in pregnancy. CASE: A 29-year-old
      primigravida, diagnosed with ARVD 1 year prior to pregnancy, underwent a full
      term, uncomplicated pregnancy and delivery while maintained on acebutolol and an
      implanted cardioverter defibrillator. Her infant was born without an apparent
      cardiac anomaly or heart rate abnormality. CONCLUSION: Successful management of
      pregnancy complicated by ARVD can be accomplished with an implanted cardioverter
      defibrillator and an antiarrhythmic agent. Such patients should be managed with
      close monitoring during pregnancy for signs and symptoms of arrhythmia and
      preventive obstetric care appropriate to their clinical profile to optimize
      normal deliveries.

PMID- 17039705
TI  - Heterotopic pregnancy after 2 prior ectopic pregnancies: a case report.
AB  - BACKGROUND: Heterotopic pregnancy is a rare occurrence, with spontaneous
      pregnancy often unsuspected and associated with delayed diagnosis. When previous
      ectopic pregnancy has been treated, future pregnancy is associated with an
      increased risk for ectopic pregnancy and potentially heterotopic pregnancy.
      Conservative treatment for ectopic pregnancy with either surgery or methotrexate
      leaves the patient with hope for potential future fertility, especially when
      assisted reproductive technology is not available. CASE: A woman who had been
      treated for ectopic pregnancy in both fallopian tubes presented with a
      spontaneous heterotopic pregnancy. CONCLUSION: Heterotopic pregnany may occur
      after treatment of previous ectopic pregnancy and may lead to a successful
      outcome when diagnosed and treated appropriately.

PMID- 17039706
TI  - Incisional bladder hernia and refractory urinary urgency after pelvic surgery: a
      case report.
AB  - BACKGROUND: Isolated incisional herniation of the bladder is very rare following
      pelvic surgery and may present as suprapubic discomfort. We report a case of
      incisional bladder hernia following pelvic surgery presenting as refractory
      urinary urgency. CASE: A 70-year-old woman, para 2, presented with a long history
      of suprapubic tenderness and refractory urinary urgency following reconstructive
      pelvic surgery. Over the 3 years following her surgery, multiple physicians
      evaluated the patient but were unable to find a definitive source of her urgency.
      She had used multiple anticholinergic agents without relief of the symptoms. A
      complete urogynecologic evaluation, radiologic imaging and high clinical
      suspicion for incisional hernia revealed a bladder hernia. Surgical exploration
      confirmed the fascial defect and bladder hernia. Herniorrhaphy corrected the
      defect and relieved the patient's symptoms of refractory urgency. CONCLUSION: An
      incisional bladder hernia may present as refractory urinary urgency following
      reconstructive pelvic surgery. Strong clinical suspicion can allow earlier
      diagnosis and surgical treatment of this rare condition. Primary herniorrhaphy
      offers successful repair of the fascial defect and resolution of the urgency
      symptoms.

PMID- 17039707
TI  - Latent pelvic tuberculosis reactivating in a postmenopausal woman: a case report.
AB  - BACKGROUND: Tuberculosis most often affects the pulmonary system; however, 8-15%
      of cases infect the genitourinary system. The primary treatment of uterine
      tuberculosis is medical therapy, and only when that fails is surgical
      intervention warranted. CASE: A 75-year-old woman presented with chronic back
      pain and fatigue. She had been on prednisone for 9 years for autoimmune hepatitis
      and had earlier exposure to tuberculosis. Evaluation led to the diagnosis of
      uterine tuberculosis. The patient was unable to tolerate a full course of
      antituberculin therapy, so she underwent an abdominal hysterectomy and bilateral
      salpingo-oophorectomy. CONCLUSION: We believe the patient had latent uterine
      tuberculosis that was reactivated from her chronic steroid use. If she had a
      purified protein derivative test prior to the start of prednisone therapy, latent
      tuberculosis may have been diagnosed and treated before she developed a
      clinically active infection.

PMID- 17039708
TI  - Small bowel volvulus after uterine artery embolization requiring bowel resection:
      a case report.
AB  - BACKGROUND: Previously described surgical complications following uterine artery
      embolization for leiomyomata include sequelae of uterine aberrant embolization
      (buttock and labial necrosis, vesicouterine fistula), prolapsed cervical myoma,
      uterine necrosis, ischemic uterine rupture and sepsis. CASE: A 43-year-old woman
      presented with severe abdominal pain, nausea and vomiting 7 days after bilateral
      uterine artery embolization for symptomatic leiomyomata. Mechanical obstruction
      of the distal ileum was diagnosed and did not respond to conservative measures.
      At laparotomy, volvulus of the distal ileum, which adhered to omental and uterine
      adhesions, required resection and end-to-end anastomosis. CONCLUSION: Volvulus
      may occur following uterine artery embolization for leiomyomata.

PMID- 17039709
TI  - Symptomatic cesarean scar diverticulum: a case report.
AB  - BACKGROUND: Extrauterine lesions of intermediate trophoblast have occurred in and
      around fallopian tubes and ovaries and are thought to result from an exaggerated
      trophoblastic response to the implantation site of a previous ectopic pregnancy.
      Additionally, cesarean scar defects have recently been identified as a source of
      persistent, irregular vaginal bleeding in women and can be identified by pelvic
      ultrasound. CASE: A 35-year-old woman presented with irregular vaginal bleeding
      in association with an anterior extrauterine cystic mass detected by pelvic
      ultrasound and thought to represent a cesarean scar defect. Subsequent histology
      revealed an endometrial diverticulum lined with chorionic-type intermediate
      trophoblast, a subpopulation of trophoblast that composes placental site nodules.
      CONCLUSION: This was the first case of a lesion of intermediate trophoblast
      occurring in a cesarean scar diverticulum.

PMID- 17039711
TI  - Huge leiomyoma in a woman with Down syndrome: a case report.
AB  - BACKGROUND: For patients with Down syndrome, the reproductive period is becoming
      longer in relation to the increasing lifetime. Thus, the possibility of
      reproductive disorders is also increasing. CASE: A 37-year-old woman with trisomy
      21 was hospitalized with uterine myomatosis, which was spreading to the
      umbilicus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were
      performed, and estrogen replacement was given after surgery. CONCLUSION: The
      incidence of solid tumors in Down syndrome patients is extremely rare or
      nonexistent. This case calls attention to reproductive pathology in long-lived
      women with Down syndrome.

PMID- 17039710
TI  - Keratinizing squamous cell carcinoma of the cervix in a sexually inexperienced
      woman: a case report.
AB  - BACKGROUND: Even though cervical cancer is largely considered to be a sexually
      transmitted disease with a viral etiology, other modes of transmission are
      theoretically possible. CASE: A 38-year-old woman with cervical squamous cell
      carcinoma adamantly denied having ever had sexual intercourse due to personal,
      religious and cultural beliefs. CONCLUSION: Because the human papillomavirus may
      be spread via nonsexual means, Pap smear screening in sexually active and
      inexperienced women is important.

PMID- 17039712
TI  - Term delivery of the second twin after miscarriage of the first: a case report.
AB  - BACKGROUND: Term delivery of the second twin after miscarriage of the first twin
      is rare. There is always a risk of preterm delivery as well as infection leading
      to chorioamnionitis. CASE: The second twin was delivered at term after
      miscarriage of the first twin at 17 weeks'gestation. The pregnancy was carefully
      monitored for prevention and early detection of chorioamnionitis. Delivery was
      delayed to 30 weeks after the miscarriage of the first twin, with a good outcome.
      CONCLUSION: Delayed delivery of the second twin with conservative management
      clearly is of benefit.

PMID- 17039714
TI  - McKinsey 'PCT support' bid sparks conflict-of-interest row.

PMID- 17039713
TI  - Pelvic pain associated with an unsuspected intraomental intrauterine device
      placed 30 years earlier: a case report.
AB  - BACKGROUND: Recent-onset chronic pelvic pain thought to originate from an
      intraomental Dalkon Shield intrauterine device (IUD) (A. H. Robbins, Inc.,
      Richmond, Virginia) that had remained asymptomatic for over 30 years is unusual.
      Case reports and patient series suggest that intraomental IUDs remain
      asymptomatic for long periods of time and are usually not associated with chronic
      pelvic pain. CASE: A 49-year-old woman with an unrecollected history of Dalkon
      Shield placement 30 years earlier was evaluated after 6 months of pelvic pain. A
      negative workup and failure of conservative management prompted an abdominal
      hysterectomy with bilateral salpingooophorectomy, which failed to relieve the
      symptoms. Revaluation identified a mobile, intraabdominal Dalkon Shield. Real
      time x-ray fluoroscopy and reverse Trendelenburg positioning were used to
      laparoscopically retrieve the IUD from the patient's benign-appearing omentum.
      The pelvic pain remained resolved for over 1 year after removal of the IUD.
      CONCLUSION: An intraomental IUD that remained asymptomatic for 30 years was the
      most likely source of chronic pelvic pain in this perimenopausal patient.
      Increased intraabdominal fat deposition associated with the perimenopause may
      have contributed to this patient's change in clinical status.

PMID- 17039715
TI  - Four in five spearhead PCTs fall behind on inequalities.

PMID- 17039716
TI  - Charities fear 'nuisance' penalties.

PMID- 17039717
TI  - Are paid-up ITC millions being consigned the scrapheap?

PMID- 17039718
TI  - On iSoft--the inside story.

PMID- 17039719
TI  - Barometer. Public health September 2006.

PMID- 17039720
TI  - Fraud. Your cheating art.

PMID- 17039721
TI  - Staff management. Soft solutions.
AB  - The projected spend on NHS agency staff for 2005-06 is around pounds sterling
      1bn. Some trusts spend significantly more than 10 per cent of their total pay
      bill on non-NHS staff. NHS Employers points to huge potential savings from e
      rostering. The software dramatically cuts time spent preparing rotas and also
      produces useful management information.

PMID- 17039722
TI  - Cutting edge care.

PMID- 17039723
TI  - Assistive technology. Home comforts.

PMID- 17039724
TI  - Health hotel: Finance. Golden wonder.

PMID- 17039725
TI  - Health hotel: welfare and health. What about the workers?

PMID- 17039726
TI  - Health hotel: access and choice. Lofty ambitions.

PMID- 17039727
TI  - Health hotel: quality of service. Safe as houses.

PMID- 17039728
TI  - [Virological diagnosis and follow-up of HIV infection. State of the art and
      situation in Tunisia].
AB  - Human immunodeficiency virus (HIV) is a retrovirus infecting approximatively 40
      million people worldwide. HIV is characterized by a great variability with
      epidemiological, diagnostic and therapeutic implications. The course of infection
      goes through three stages (acute infection, clinical latency and AIDS) with the
      evolution of virological markers (anti-HIV antibodies, p24 antigenemia, plasma
      RNA and proviral DNA). Direct virological diagnosis is mainly based on molecular
      tools allowing viral genome detection and amplification with specific primers and
      nucleic probes besides p24 antigenemia detection, and more rarely viral culture.
      Antigenic properties of viral proteins elicit in infected patients antibody
      synthesis, which is detected using serology (ELISA and Western blot tests). The
      follow-up of infected patients is carried out with plasma HIV-1 RNA quantitation
      and phenotypic or genotypic characterization of variant isolates. Virological
      tests are prescribed according to clinical presentation (screening, acute
      infection, newborn from HIV-infected mother). Most of these virological tools are
      available in Tunisia, allowing both diagnosis of HIV infection and monitoring of
      infected individuals. Regarding diagnostic tests indication and interpretation,
      multidisciplinary concertation is hopeful in order to optimize patient
      management.

PMID- 17039729
TI  - [Microscopic colitis. A 20 cases series].
AB  - Microscopic colitis are defined as a chronic inflammation of a normal macroscopic
      colonic mucosa. We report 20 cases of microscopic colitis. Chronic diarrhea
      revealed the diagnosis in 95% of cases. Endoscopic examination was normal in 95%
      of patients. We diagnosed collagenous colitis in 65% of cases and lymphocytic
      colitis in 35% of cases. The treatment was based on sulphasalazine in 16
      patients, on 5 aminosalicylic acid in 1 case, on gluten free diet in 2 cases and
      a symptomatic treatment was prescribed to one patient. A clinical remission was
      observed in 41.2% of patients taking sulphasalazine.

PMID- 17039730
TI  - [Superficial fungal infections. Epidemiologic, clinical and mycologic study over
      a three year period].
AB  - The object of our study is to release the epidemiological, clinical and
      mycological characteristics of superficial fugal infections. A retrospective
      study was carried out during three years (1996-1998). Direct microscopy was
      positive in 86% cases, the culture in 62% cases. Trichophyton rubrum accounts for
      85% of the dermatophytic flora. The superficial fugal infections account for 15%
      of the reasons for consultation in our service. They would touch according to
      data's of literature 2 to 13% of the general population. Trichophyton rubrum in
      accordance with the various series published, is the fungi most frequently
      insulated with variable rates between 46 and 82% of the superficial fungal
      infections. Any time, Candida albicans is prevalent on the level of the hands.

PMID- 17039732
TI  - [Epidemiologic and clinical features of patients with type 2 diabetes mellitus in
      primary care facilities (Sousse, Tunisie)].
AB  - As a result of epidemiologic transition, diabetes mellitus became a major public
      health problem in Tunisia. We tried to determine the epidemiological and clinical
      features of patients with type 2 diabetes mellitus in primary health care units
      in Sousse (Tunisia). It was a cross sectional study about a stratified sample of
      404 type 2 diabetes mellitus patients followed in primary care offices in Sousse
      in 2003. Average age was 60 + 10.9 years and sex-ratio was 0.5. Hypertension and
      obesity were found in respectively 71.3% and 37.6%. Diabetic neuropathy was the
      most frequent degenerative complication (41.1%) followed by diabetic retinopathy
      (18.3%). Thus, type 2 diabetes mellitus patients, followed in primary care units
      show a high cardiovascular risk with serious and frequent complications. That's
      why, the national care program of type diabetes mellitus, in primary health care
      should take in consideration, in its guidelines, the clinical and epidemiological
      characteristics of these patients.

PMID- 17039731
TI  - [Premature ovarian insufficiency. Analysis of 30 cases].
AB  - Premature menopause is a relatively rare disease but it has delicate consequences
      dominated by infertility problems. Most often, etiologic investigation is
      disappointing. Helped in some cases by the association to some auto-immune
      diseases or a previous treatment with chemotherapy or an irradiation may be
      useful to understand the origin of the premature ovarian failure. We analyse in
      this paper 30 cases of premature menopause to try to precise its etiologic
      factors, its diagnosis tools, the fertility prognostic and the therapeutic
      possibilities

PMID- 17039733
TI  - [Mal de Meleda. 16 cases].
AB  - Mal de Meleda is a recessive transgression palmoplantar keratoderma. We report
      the epidemiological, clinical and progressiveness aspects of the disease in 16
      patients of a large consanguineous tunisian family. The age ranged from 3 to 90
      years. Nine were male and 7 female patients. Onset in early infancy was
      characterized by erythema of the palms and soles, followed by a diffuse yellowish
      hyperkeratosis. Thickness of the dorsal aspect of the fingers started in
      childhood. Extension of hyperkeratosis to the dorsal of the hand were reported
      only in adults and usually precede the involvement of the feet Palmoplantar
      hyperhidrosis with fetid odor between the toes was frequently seen as well as
      conical distal phalanges. In some adults keratoderma gave contracture of the
      fingers leading to limitation of movements Mal de Meleda must be differentiated
      from other recessive palmoplantar keratoderma such as Papillon-Lefevre syndrome
      and Mal de Naxos. the remaining inherited palmoplantar keratoderma being
      autosomal dominant. Mal de Meleda is a rare disease but is still relatively
      frequent in some tunisian regions, due to the high rate of consanguinity Mal de
      Meleda remains an afflicting and disabling disease.

PMID- 17039734
TI  - Co-analgesic effect of ketorolac after thoracic surgery.
AB  - Thoracotomies are painful surgical procedures and adequate pain relief is
      associated with improved respiratory function and fewer respiratory
      complications. After thoracotomy for lung resection, patients received morphine
      based patient-controlled analgesia (PCA). Three groups were prospectively and
      randomised investigated: patients receiving preemptive ketorolac, those given
      postoperative ketorolac and controls. No differences among groups were found for
      demographic data, anaesthesia and surgery durations, or for the amounts of
      anaesthesia drugs administered. The blood losses were also comparable: 565 +/-
      374 ml for the preemptive ketorolac group. 749 +/- 491 ml for the postoperative
      ketorolac group and 674 +/- 323 ml for the controls. At 48 h after surgery,
      compared to controls, morphine consumption was 36% lower for the preemptive
      ketorolac group and 17% lower for postoperative ketorolac group (p < 0.05). No
      statistically significant differences were observed for pulmonary function tests.
      These results suggest that non-steroidal anti-inflammatory drugs can reduce the
      opioid requirements after thoracic surgery but do not improve lung function.

PMID- 17039735
TI  - [Clinical features and treatment in Cushing's disease. 18 cases].
AB  - We report a retrospective study about 18 Cushing's diseases in the department of
      endocrinology at Charles Nicolle hospital in 24 years. The mean age was 33.7
      years with a male-female ratio of 4/14. Diagnosis was established on
      adrenocorticotropin hormone analysis and pituitary imaging. Transsphenoidal
      adenomectomy was released in 8 cases of Cushing's disease, it was successful in 5
      patients (62.5%). Bilateral adrenalectomy was performed in three cases.

PMID- 17039736
TI  - [Radon in Tunisian buildings].
AB  - Radon is a natural radioactive gas produced by decay of uranium and radium
      present in soils. Diluted in air, in confined atmospheres, it may accumulate in
      high concentrations. Inhalation of radon and its progeny is thought to increase
      lung cancer risk. For the first time, air radon concentrations were determined in
      1151 dwellings situated in all the inhabited regions of Tunisia, using open alpha
      track dosimeters exposed during two months. The median of 1864 measurements was
      36 Bq m(-3) (with a maximum of 512 Bq m(-3), most of them being less than 100 Bq
      m(-3). All results were under the International Instances recommended range.

PMID- 17039737
TI  - [Adult-onset Still disease. 11 cases].
AB  - Still's Disease of the adult is a systemic disease that the cause is unknown. If
      the pediatric forms are frequent, the affection of the adult is rare and its
      diagnosis is difficult. The purpose of this study is to analyse the features of
      the clinical evolution of adult Still's disease and to compare our results with
      the literature. It is a retrospective study about 21 years that permitted to
      collect 11 cases according the criteria of Yamaguchi. It is a matter of 6 men and
      5 women that the mean age is 31 years old (age range: 16 to 48 years old). The
      fever was constant, the skin rash was noticed in 8 patients (72.7%); a
      polyarthritis was noticed in all the patients, chronic in 10 cases (90.9%) which
      2 erosive forms. Adenopathies were present in 5 patients, a splenomegaly and a
      hepatomegaly were noticed respectively in 4 and 2 cases. Inflammatory syndrome
      with hyperleukocytosis was constant, and a hepatic cytolysis was noticed in 80%.
      The total ferritinemia titrated in 8 patients was constantly high. The
      hemocultures realized in all the patients were sterile and the complete
      immunologic examination was negative. The strong dose of corticoid was prescribed
      with success in all the patients. The immediate evolution was favourable in 10
      patients. We deplore one death after a state of deep denutrition. Still's disease
      of the adult is rare, its diagnosis is difficult, sensitive to corticotherapy and
      its clinical evolution in our country is comparable to the literature.

PMID- 17039738
TI  - [Giant placental chorioangioma].
AB  - The large placental chorioangioma is a non-trophoblastic vascular tumor of
      placenta which size is more than 4 cm. It's a rare tumor, the incidence is
      between 1/3500 and 1/9000 birth. We analyze, on base of our case and from a
      literature review, the ultrasonography aspects of this tumor: we bring out also
      the physiological mechanisms of maternal and fetal complications and finally we
      detail the therapeutic possibilities. Chorioangioma appears in ultrasound scan
      like a thoroughly limited hypo-echogenic zone The vascular origin of the tumor
      can be confirmed by color Doppler. A left-right shunt effect results from arterio
      venous communications and causes backwardness growth and fetal death in-utero The
      fetus is exposed to anemia and microangiopathic thrombopenia The maternal
      complications are: hydramnios, abruption placenta, premature ruptured membrane.
      Therapeutic possibilities are reduced: In several fetal anemia, blood transfusion
      can be done. Some techniques for tumor devascularization are be tried by someone.

PMID- 17039739
TI  - [Inflammatory fibroid polyp of the ileum presenting as intussusception: a case
      report in an adolescent].
AB  - Inflammatory fibroid polyp is an uncommon and benign submucosal lesion of the
      gastrointestinal tract. The maximal incidence is in the fifth and sixth decades.
      The main histological characteristics are diffuse inflammatory infiltrate with
      eosinophils and highly vascularized fibrocystic stroma. We report a case of 15
      year-old patient who underwent emergency surgery because of acute intestinal
      obstruction as a result of an intussusception. The macroscopical study after
      segmental ileal resection showed a nodular lesion 3x2x2 cm, arising from the
      submucosa with an ulcerated surface. The pathologic diagnosis was ileal
      inflammatory fibroid polyp. Immunohistochemically, the cells reacted with
      vimentin and CD34. It has no malignant potential although extensive infiltration
      may occur. The etiology is unknown. We discuss the clinical, the pathological
      aspects and the possible etiological factors of the inflammatory fibroid polyp.

PMID- 17039740
TI  - [Prune belly syndrome: early prenatal diagnosis and management].
AB  - Prune Belly syndrome is characterized by a combination of megacystis, anterior
      abdominal wall distension with deficiency of the abdominal wall musculature, and
      bilateral cryptorchidism. Diagnosis is easy after 15 weeks of gestation, but may
      be difficult at the end of the first term. Authors report 2 cases of Prune Belly
      syndrome diagnosed at 11 and 14 weeks of gestation respectively. After literature
      review, diagnosis and prognosis particularities of this syndrome are discussed.

PMID- 17039741
TI  - [Pelvic ganglioneuroma. Report of a case].
AB  - Ganglioneuroma is a rare benign tumor. It is the most mature of neurogenic
      tumors. We report a case of a pelvic ganglioneuroma diagnosed in 24-year-old
      pregnant woman who presented with an urinary infection. Echographic examination
      suggested an ovarian mass. At surgical operation, the tumor was close to the
      sacrum. A total resection of the tumor was performed. Pathological examination
      proved it as a ganglioneuroma. Sixteen months later, the patient is free from
      disease.

PMID- 17039742
TI  - [Deficient expression of leukocyte adhesion proteins. A new Tunisian case].
AB  - Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency inherited
      as an autosomal recessive genetic disorder. LAD was suspected in a four days old
      girl. She was born from healthy first cousins. A family history of a boy who died
      from omphalitis and sepsis was reported. Our patient had the severe form, she had
      delayed umbilical cord separation and suffered recurrent infections. She had a
      deletion of the G at position 1497. The patient received bone marrow
      transplantation from her HLA-identical mother at age of 14 months. She is now 9
      years old and in good health.

PMID- 17039743
TI  - Clarification of guidelines for the proper use of child car seats.

PMID- 17039744
TI  - Health care for the homeless in America.

PMID- 17039745
TI  - Imperative integration: medical care for older patients.

PMID- 17039746
TI  - Vaccines for preventing influenza in healthy children.

PMID- 17039747
TI  - Expectant management vs. surgical treatment for miscarriage.

PMID- 17039748
TI  - Exercises for mechanical neck disorders.

PMID- 17039749
TI  - The homeless in America: adapting your practice.
AB  - In 2004, the National Guidelines Clearinghouse placed eight guidelines from the
      National Health Care for the Homeless Council on its Web site. Seven of the
      guidelines are on specific disease processes and one is on general care. In
      addition to straightforward clinical decision making, the guidelines contain
      medical information specific to patients who are homeless. These guidelines have
      been endorsed by dozens of physicians who spend a large part of their clinical
      time caring for some of the millions of adults and children who find themselves
      homeless each year in the United States. In one guideline, physicians are
      prompted to keep in mind that someone living on the street does not always have
      access to water for taking medication. Another guideline points out the
      difficulty of eating a special diet when the patient depends on what the local
      shelter serves. As the number of homeless families and individuals increases,
      family physicians need to become aware of medically related information specific
      to this population. This can help ensure that physicians continue to offer
      patient-centered care with minimal adherence barriers.

PMID- 17039750
TI  - Kawasaki disease: summary of the American Heart Association guidelines.
AB  - Kawasaki disease is an acute vasculitis of childhood that predominantly affects
      the coronary arteries. The etiology of Kawasaki disease remains unknown, although
      an infectious agent is strongly suspected based on clinical and epidemiologic
      features. A genetic predisposition is also likely, based on varying incidences
      among ethnic groups, with higher rates in Asians. Symptoms include fever,
      conjunctival injection, erythema of the lips and oral mucosa, rash, and cervical
      lymphadenopathy. Some children with Kawasaki disease develop coronary artery
      aneurysms or ectasia, ischemic heart disease, and sudden death. Kawasaki disease
      is the leading cause of acquired heart disease among children in developed
      countries. This article provides a summary of the diagnostic and treatment
      guidelines published by the American Heart Association.

PMID- 17039751
TI  - Information from your family doctor. Kawasaki disease: what you should know.

PMID- 17039752
TI  - Preventive health counseling for adolescents.
AB  - The leading causes of adolescent mortality are accidents (death from
      unintentional injury), homicide, and suicide. Additional morbidity is related to
      drug, tobacco, and alcohol use; risky sexual behaviors; poor nutrition; and
      inadequate physical activity. One third of adolescents engage in at least one of
      these high-risk behaviors. Physicians should specifically target these risk
      factors with preventive counseling, although adolescents may be reluctant to
      initiate discussions about risky behaviors because of confidentiality concerns.
      The key to providing relevant and useful preventive counseling for adolescent
      patients is developing the trust necessary to discuss the specific issues that
      impact this age group.

PMID- 17039753
TI  - A practical guide to crisis management.
AB  - Family physicians often treat patients who are experiencing psychological or
      medical crises. Any event perceived as overwhelming by the patient may trigger a
      crisis reaction consisting of psychological and physiological symptoms.
      Physicians are encouraged to assist patients who are experiencing a crisis by:
      (1) providing reassurance and support; (2) evaluating the nature of the problem
      and determining the patient's mental, psychiatric, suicidal or homicidal, and
      medical statuses; (3) ensuring the safety of the patient and others; (4)
      assisting the patient in developing an action plan that minimizes distress, and
      obtaining patient commitment to the plan; and (5) following up with the patient
      and other relevant persons to ensure follow-through, assess progress, and provide
      additional assistance and support. Medication or referral for psychiatric or
      psychological counseling may be necessary for patients with continuing problems.

PMID- 17039754
TI  - Information from your family doctor. Crisis management.

PMID- 17039755
TI  - Growing plantar lesion following trauma.

PMID- 17039756
TI  - Information from your family doctor. Colds and the flu: tips for feeling better.

PMID- 17039757
TI  - Information from your family doctor. Sore throat.

PMID- 17039758
TI  - Information from your family doctor. Antibiotics: when they can and can't help.

PMID- 17039759
TI  - Facilitating shared decision making with patients.

PMID- 17039760
TI  - In search of a best practice model for the hospital-foundation relationship.

PMID- 17039761
TI  - Gaining a competitive edge: e-philanthropy and hospital development.
AB  - E-philanthropy offers tremendous potential for hospital development. Using the
      Internet, a hospital can efficiently communicate with current and prospective
      donors, reach donors that it otherwise would not reach, and build stronger
      relationships with the next generation of major and planned givers. Developing a
      strategic online program will help hospitals and their associated foundations
      achieve greater success and more effectively fulfill their missions well into the
      future.

PMID- 17039762
TI  - Tapping the river of grateful patients: principles and techniques for best
      practices in patient prospecting.

PMID- 17039763
TI  - Build it and they will come.

PMID- 17039764
TI  - Acceptable noise level: A clinical measure for predicting hearing aid outcome.

PMID- 17039765
TI  - Acceptable noise level as a predictor of hearing aid use.
AB  - Acceptable noise level (ANL) measures a listener's reaction to background noise
      while listening to speech. Relations among hearing aid use and ANL, speech in
      noise (SPIN) scores, and listener characteristics (age, gender, pure-tone
      average) were investigated in 191 listeners with hearing impairment. Listeners
      were assigned to one of three groups based on patterns of hearing aid use: full
      time use (whenever hearing aids are needed), part-time use (occasional use), or
      nonuse. Results showed that SPIN scores and listener characteristics were not
      related to ANL or hearing aid use. However, ANLs were related to hearing aid use.
      Specifically, full-time hearing aid users accepted more background noise than
      part-time users or nonusers, yet part-time users and nonusers could not be
      differentiated. Thus, a prediction of hearing aid use was examined by comparing
      part-time users and nonusers (unsuccessful hearing aid users) with full-time
      users (successful hearing aid users). Regression analysis determined that unaided
      ANLs could predict a listener's success of hearing aids with 85% accuracy.

PMID- 17039766
TI  - Acceptable noise level: reliability measures and comparison to preference for
      background sounds.
AB  - The present study (1) assessed the reliability of the acceptable noise level
      (ANL) measure using speech-spectrum and speech-babble noises as the competing
      stimuli, and (2) investigated the relationship between ANL and preference for
      background sounds in 30 young adults with normal hearing sensitivity. Listeners
      were evaluated during three test sessions approximately one week apart. Results
      demonstrated that ANLs are highly reliable over short periods of time,
      independent of the background noise distraction. Mean ANLs, however, were
      affected by type of background noise distraction, indicating ANLs obtained using
      different competing stimuli should not be compared directly. Results further
      demonstrated that participants' ratings of preference for background sound were
      consistent over time; however, listeners' preference for background sound was not
      related to their acceptance of background noise (i.e., ANL). This may indicate
      listeners cannot accurately assess their ability to accept background sounds, at
      least with the questionnaire used in the present study.

PMID- 17039767
TI  - Acceptance of background noise levels in bilingual (Korean-English) listeners.
AB  - The acceptable noise level (ANL) is the maximum amount of background noise that
      listeners are willing to accept while listening to speech. ANL has not been
      studied in listeners who use languages other than English. The purpose of this
      study was to explore whether ANLs obtained from Korean listeners in both English
      and Korean were comparable to ANLs obtained from monolingual English listeners.
      The results showed that ANLs obtained in English (ANL-E) did not differ
      significantly for the bilingual and monolingual listeners. Additionally, a cross
      language comparison, within bilinguals, showed that ANLs obtained using Korean
      (ANL-K) speech stimuli were not significantly different from ANL-E. Finally,
      speech perception in noise did not correlate with ANLs in English or Korean for
      the bilingual listeners. Results suggest that the ANL measure is language
      independent within bilinguals and may be of potential clinical use in minority
      language groups.

PMID- 17039768
TI  - Acceptance of noise with monaural and binaural amplification.
AB  - The present study investigated the effects of monaural and binaural amplification
      on speech understanding in noise and acceptance of noise for 39 listeners with
      hearing impairment. Results demonstrated that speech understanding in noise
      improved with binaural amplification; however, acceptance of noise was not
      dependent on monaural or binaural amplification for most listeners. These results
      suggest that although two hearing aids maximize speech understanding ability in
      noise, most individuals' acceptance of noise, which is directly related to
      hearing aid use, may not be affected by the use of binaural amplification. It
      should be noted that monaural amplification resulted in greater acceptance of
      noise for some listeners, indicating that binaural amplification may negatively
      affect some individuals' willingness to wear hearing aids. It should also be
      noted that interaural differences in acceptance of noise might exist for some
      listeners; therefore, if only one hearing aid is fitted, monaural ANLs should be
      measured.

PMID- 17039769
TI  - Differences in responses from the cochleae and central nervous systems of females
      with low versus high acceptable noise levels.
AB  - Studies of acceptable noise level (ANL) consistently report large intersubject
      variability in acceptance of background noise while listening to speech. This
      variability is not related to age, gender, hearing sensitivity, type of
      background noise, speech perception in noise performance, or efferent activity of
      the medial olivocochlear pathway. An exploratory study was conducted to determine
      if differences in aggregate responses from the peripheral and central auditory
      system can account for intersubject variability in ANL. Click-evoked otoacoustic
      emissions (CEOAEs), binaural auditory brainstem responses (ABRs), and middle
      latency responses (MLRs) were measured in females with normal hearing with low (n
      = 6) versus high (n = 7) ANLs. Results of this preliminary study indicate no
      differences between the groups for CEOAEs or waves I or III of the ABR.
      Differences between the two groups emerge for the amplitudes of wave V of the ABR
      and for the Na-Pa component of the MLR, suggesting that physiological variations
      arising from more central regions of the auditory system may mediate background
      noise acceptance.

PMID- 17039770
TI  - [Advances in the study of nucleoside antiviral drugs].

PMID- 17039771
TI  - [Recent advances in the study of pharmacological activities and solid-phase
      synthesis of indoles and their analogues].

PMID- 17039772
TI  - [Advances in the study of cardiac M3 receptor as a novel target of antiarrhythmic
      drugs].

PMID- 17039773
TI  - [Comparison of the inhibitory activities of salvianolic acid B and Ginkgo biloba
      extract EGb 761 on neurotoxicity of beta-amyloid peptide].
AB  - AIM: To compare the effects of salvianolic acid B (Sal B) and Ginkgo biloba
      extract EGb 761 on beta-amyloid peptide (beta-AP) fibril formation and
      cytotoxicity to PC12 cells. METHODS: The inhibitory effects of Sal B and EGb 761
      on beta-AP1-40 fibril formation were determined by using fluorescence analysis
      with Thioflavin T (ThT) and electron microscopic image. beta-AP25-35 was aged by
      incubating at 37 degrees C for 7 d, then the protein was incubated with PC12
      cells. The protective effects of Sal B and EGb 761 against cytotoxicity induced
      by aged beta-AP25-35 in PC12 cells were evaluated by MTT reduction assay and flow
      cytometric analysis. beta-AP25-35-induced accumulation of intracellular reactive
      oxygen species (ROS) was determined by fluorescence analysis. RESULTS: Both Sal B
      and EGb 761 inhibited the formation of amyloid fibrils, protected PC12 cells from
      beta-AP25-35-induced cytotoxicity, and decreased ROS accumulation caused by beta
      AP25-35. The effective doses of Sal B were far lower than those of EGb 761.
      CONCLUSION: Sal B was much more efficient than EGb 761 in inhibiting beta-AP
      aggregation and in protecting PC12 cells from beta-AP-induced cytotoxicity.

PMID- 17039774
TI  - [Effect of inducible nitric oxide synthase on tumour cells sensitivity to
      mitomycin C analogue 629 in vitro].
AB  - AIM: To examine the effect of inducible nitric oxide synthase (iNOS) on tumour
      cells chemosensitivity to mitomycin C (MMC) analogue 5-aziridinyl-3-hydroxyl-1
      methylindole-4,7-dione (629) in vitro, and elucidate the possible role of iNOS in
      the metabolism of 629. METHODS: Human sarcoma cells (HT1080) and its iNOS gene
      transfected clones (iNOS9, iNOS12) were exposed to 629 at concentrations of 1
      nmol x L(-1) - 100 micromol x L(-1). 3-[4, 5-Dimethylthiazol-2-yl] -2,5
      diphenyltetrazolium bromide (MTT) assay, agarose electrophoresis and flow
      cytometric analysis were used to determine cell sensitivity, deoxyribonucleic
      acid (DNA) damage and the change of cell cycle in above process, respectively.
      All experiments were performed both in air and under hypoxia parallelly. RESULTS:
      629 was more toxic than MMC, and enhanced cytotoxicity under hypoxia, which
      resulted in cell necrosis. Sixteen hours after treated with 629, HT1080 cells and
      related iNOS-transfected clone cells were obviously blocked in G2/M phase.
      CONCLUSION: iNOS plays dual roles in 629 metabolism, enhancing or decreasing the
      cytoxicity of 629 depending on the intracellular oxygen pressure P(O2), which
      caused higher cytotoxicity to hypoxia cells of 629 with the increasing of iNOS
      activity.

PMID- 17039775
TI  - [Action of AMP579 and adenosine on potassium or sodium ionic channels in isolated
      rat and guinea pig ventricular myocytes].
AB  - AIM: To study the effect of AMP579 and adenosine on potassium ionic (K+) or
      sodium ionic (Na+) channels and to elucidate ionic mechanisms underlying negative
      inotropic and antiarrhythmic effects of AMP579 and adenosine. METHODS: Ionic
      channel currents of rat and guinea pig ventricular myocytes were recorded by
      patch clamp technique in whole-cell configuration. RESULTS: Adenosine showed a
      stronger activating effect on transient outward K+ current (I(to)) than AMP579,
      EC50 of adenosine and AMP579 were 2.33 and 8. 32 micromol x L(-1), respectively
      (P < 0.05). An adenosine A1 receptor blocker, 1,3-dipropyl-8-cyclopentylxanthine
      (PD116948), can abolish the effects of AMP579 and adenosine on I(to),
      demonstrating that the effect is mediated by adenosine A1 receptor. Adenosine
      exerted a more obvious inhibitory effect on delayed rectifier K+ current (IK)
      than AMP579. IC50 of adenosine and AMP579 were 1.21 and 2.31 micromol x L(-1),
      respectively (P < 0.05). AMP579 had a more powerful inhibitory effect on inward
      rectifier K+ current (IK1) than adenosine. IC50 of AMP579 and adenosine were 4.15
      and 20.7 micromol x L(-1), repectively (P < 0.01). AMP579 and adenosine exerted a
      similar inhibitory effect on fast inward Na+ current (INA), IC50 of AMP579 and
      adenosine were 9.46 and 6.23 micromol x L(-1), respectively (P > 0.05).
      CONCLUSION: Adenosine showed a stronger activating effect on I(to) than AMP579,
      however, the mechanism of AMP579 and adenosine activating I(to) was mediated by
      adenosine A1 receptor. AMP579 has a more powerful inhibitory effect on IK1, and
      less inhibitory effect on IK than adenosine. Both drugs have a similar inhibitory
      effect on INa. The negative inotropic and antiarrhythmic effects are related to
      these ionic mechanisms.

PMID- 17039776
TI  - [Establishment of a reporter gene-based cell screening model for discovering new
      agonists of estrogen receptor beta subtype].
AB  - AIM: To establish a sensitive and efficient reporter gene-based screening model
      for finding agonists of estrogen receptor beta subtype. METHODS: A recombinant
      vector pTAL-ERE-SEAP was constructed by inserting a synthetic sequence composed
      of five estrogen responsive elements in front of promoter of pTAL-SEAP vector.
      pTAL-ERE-SEAP was then transfected into human embryonic kidney (HEK293) cells.
      G418 (200 microg x mL(-1)) was added to select positive clones that can be
      induced by E2 to express reporter gene SEAP. The speciality was tested by several
      ligands of relative nuclear receptors of the same family. The stability of the
      model, the time-effect relationship, the dose-response relationship, and the
      immunocytochemistry staining of ERbeta expression after transfection were
      observed. 2 622 compounds were screened by using this model. RESULTS: Stably
      transfected clones were obtained. The expression levels of reporter gene SEAP of
      positive clones was induced by E2 in a dose-response and time-effect relationship
      manners. The Z' factor value was 0.7. The expression levels of dexamethasone and
      other ligands were low. The result of immunocytochemistry staining showed the
      expression of ERbeta. E2 had no proliferating effects on stably transfected
      clones. CONCLUSION: Stably transfected positive clones transfected with
      recombinant vector pTAL-ERE-SEAP were obtained. The positive clones may be used
      to screen for agonists of estrogen receptor beta subtype by measurement of
      luminescent value of expressed SEAP in wells of microlitre plate.

PMID- 17039777
TI  - [The design and synthesis of 2-aminothiazole derivatives and their inhibitory
      activity on apoptosis].
AB  - AIM: To investigate the inhibitory effect of 2-aminothiazole derivatives on Neuro
      cell apoptosis and QSAR. METHODS: The 2-aminothiazole derivatives were designed
      and synthesized based on the lead compound of PFT-alpha, the protective action of
      the compounds I and II against and their inhibitory action on PC12 cell apoptosis
      induced by H2O2 were determined by MTT method and FCM method. The QSAR equation
      was obtained from Cerius2-QSAR+ module. RESULTS: Eleven novel 2-aminothiazole
      Schiff base compounds (II) have been designed and synthesized. The structure of
      the compound II were characterized by IR, MS,1H NMR, 13C NMR. Their protective
      action against and the inhibitory action on PC12 cell apoptosis induced by H2O2
      were found in this experiment. The optimal QSAR equation obtained from the
      Cerius2-QSAR+ module by using log (1/EC50) with corresponding descriptors is
      Activity = 6.947 68 - 0.088 72 x "LUMO" - 0.043 018 x "Alogp98" - 0.128 752 x
      "Rad0fGration" + 0.018 246 x "Dipole-mag". The correlation statistics parameters
      of the above equation are as follows: r2 = 0.970, F-test = 49. 149, r = 0. 985
      and Lse = 0. 001. CONCLUSION: The 2-aminothiazole derivatives exhibited certain
      activity in inhibiting PC12 cell apoptosis induced by H2O2. Some compounds such
      as I-6, I-9 and II-6 have the dual activities, the protective action against and
      inhibitory action on PC12 cell apoptosis induced by H2O2. The QSAR equation
      indicated that it is favorable for enhance the activity of 2-aminothiazole
      derivatives by the reduction of "radius of gyration" and the energy of "LUMO" of
      the compounds.

PMID- 17039778
TI  - [Chemical constituents of Knoxia valerianoides].
AB  - AIM: To study the chemical constituents of Knoxia valerianoides Thorel et Pitard.
      METHODS: Chromatographic methods were used for the isolation and purification.
      Structures were elucidated on the basis of chemical analysis and spectroscopic
      data. RESULTS: Three anthraguinones were isolated from K. valerianoides and
      identified as 1, 3, 5-trihydroxy-2-methyl-6-methoxyl-anthraguinone (kaoxiadin,
      I), 1, 3, 6-trihydroxy-5-ethoxylmethyl-anthraguinone (II) and 1, 3-dihydroxy-2
      methylanthraguinone (rubiadin, III). CONCLUSION: Compound II is a new
      anthraguinone constituent.

PMID- 17039779
TI  - Water-soluble phenolic glycosides from the whole plant of Bulbophyllum
      odoratissimum.
AB  - AIM: To investigate the water-soluble phenolic glycosides from the whole plant of
      Bulbophyllum odoratissimum. METHODS: Column chromatography techniques were used
      to isolate the chemical constituents, physico-chemical constants and
      spectroscopic analysis were employed for structural elucidation. RESULTS:
      Bulbophyllinoside (1), a new phenolic glycoside and three known compounds were
      isolated from the whole plant of Bulbophyllum odoratissimum Lindl. Their
      structures were determined as 3-hydroxyphenethyl alcohol 4-O-( 6'-O-beta
      apiofuranosyl) -beta-D-glucopyranoside (1), 3-methoxyphenethyl alcohol 4-O-beta-D
      glucopynanoside (2), 3, 5-dimethoxyphenethyl alcohol 4-O-alpha-D-glucopynanoside
      (3) and syringin (4). CONCLUSION: Bulbophyllinoside (1) is a new compound.

PMID- 17039780
TI  - [Determination of ginsenoside Rd and its metabolites in rat urine by LC-MS].
AB  - AIM: To study the metabolic pathways of ginsenoside Rd in rats. METHODS: Urine
      samples were collected before and after 24 h of single oral administration of 150
      mg and intravenous administration of 60 mg of ginsenoside Rd to six rats,
      separately. The samples were purified by SPE column and then were analyzed by
      liquid chromatography-ESI-mass spectrometry for putative metabolites. RESULTS:
      Parent drug and its seven metabolites were identified in rat urine based on
      comparing total ion chromatograms of the blank with the metalolic urine as well
      as mass spectra. Its main metabolic pathways and possible structures are
      elucidated. CONCLUSION: Oxidation, combination and deglucosylation were found to
      be the major metabolic pathway of ginsenoside Rd in rats.

PMID- 17039781
TI  - [RP-HPLC fingerprint for quality assessment of Radix Angelicae dahuricae].
AB  - AIM: To establish the RP-HPLC fingerprint analysis for the quality control of
      Radix Angelicae dahuricae. METHODS: HPLC fingerprint analysis method of Radix
      Angelicae dahuricae was developed. Kromasil C18 column (250 mm x 4.6 mm ID, 5
      microm) was used, with mixture of acetonitrile and water as mobile phase in a
      gradient mode. The flow rate was 1.0 mL x min(-1). The wavelength of measurement
      was 254 nm. Twenty-one batches of Radix Angelicae dahuricae were determined.
      RESULTS: The 21 samples were classified as 4 clusters by cluster analysis and the
      11 superior in producing area samples were confirmed to establish the mutual
      model. The samples' quality was assessed by Similarity Evaluation System for
      Chromatographic Fingerprint of TCM 2004. CONCLUSION: The method can be used to
      identify and evaluate the quality of Radix Angelicae dahuricae conveniently.

PMID- 17039782
TI  - [Biliary excretion of genistein and its metabolite at different doses in rats].
AB  - AIM: To study the biliary excretion of genistein and its metabolite at different
      doses in rats. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally
      administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At
      various time intervals, the bile was collected. The bile was treated with beta
      glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL
      mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was
      removed into the tubes and then evaporated in ventilation cabinet. The residue
      was dissolved in 50 microL of methanol. Twenty microL solution was drawn and
      detected by high-performance liquid chromatography. RESULTS: The accumulative
      biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and
      (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1),
      respectively. The total drug (genistein plus glucuronidated genistein) excreted
      from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84)
      microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17%
      at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION: The
      genistein was excreted mainly in the form of glucuronidated genistein in rat
      bile. The genistein and glucuronidated genistein were excreted in a nonlinear
      dose-dependent manner.

PMID- 17039783
TI  - [Peptide mapping analysis of recombinant human interleukin-11 with HPLC-ESI-Q
      TOF/MS spectrometry].
AB  - AIM: To analyze the peptide mapping of recombinant human interleukin-11 (rhIL-11)
      by HPLC-ESI-Q-TOF/MS spectrometry. METHODS: The trypsin digested rhIL-11 at 37
      degrees C over night, and the peptide mapping was performed by HPLC. The relative
      molecular weight of the peptides fragments was measured by ESI-Q-TOF/MS, and
      amino acid sequence was analyzed by MS/MS. RESULTS: The peptide fragments of rhIL
      11 in the peptide mapping were assigned by analyzing the retain time, relative
      molecular weight and amino acid sequence. And 97% of the expected peptides were
      detected in this way. CONCLUSION: The study proves that HPLC-ESI-Q-TOF/MS is a
      good method to analyze peptide mapping of protein with the advantage of
      sensitivity, high speed and accuracy.

PMID- 17039784
TI  - [Preparation, characterization, and pulmonary delivery of rifapentine liposomes
      modified by lauric diethanolamide].
AB  - AIM: To prepare rifapentine (RIF) liposomes modified by surfactants for studying
      their the water-solubility, drug loading effeciency, release rate and pulmonary
      drug delivery. METHODS: The film method was used to prepare RIF liposomes. Of
      verious RIF liposomes morphology by lauric diethanolamide (LDEA), Tween 80 and
      azone, the properties were studied, envolving morphology, entrapment drug release
      rate and dissected lung-membrance penetration rate of swine. Pulmonary delivery
      study was carried out through bronchoscope. RESULTS: The particle size of RIF
      LDEA liposomes was between 15 - 50 nm. The top entrapment efficiency reached
      83.0%. The apparent coefficient of membrane penetration (Kp) was 44.29. LD50 was
      675 mg x kg(-1) by iv. CONCLUSION: LDEA increased the water-solubility, loading
      effeciency and release rate of RIF liposomes. The prepared RIF-LDEA liposomes
      were suitable for the treatment of pulmonary tubrculosis through bronchoscope.

PMID- 17039785
TI  - [Preparation of verapamil hydrochloride controlled-onset extended-release pellets
      and its pharmacokinetics in dogs].
AB  - AIM: To prepare verapamil hydrochloride controlled-onset extended-release pellets
      (VH-COERP) and study its release behavior in vitro. To compare the
      pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral
      administration of VH-COERP and verapamil hydrochloride delayed-release pellets
      (VH-DRP) as reference. METHODS: The core of VH-COERP were prepared in the
      fluidized bed (mini-glatt) by spraying water solution containing drugs onto
      sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner
      coating swelling layer and ethylcellulouse aqueous dispersion as the outer
      coating controlled layer. Through modifying the coating level of inner and outer
      layer, the VH-COERP with the optimized cumulative release profile was obtained.
      The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors
      after oral administration of VH-COERP and VH-DRP at different times were studied
      by RP-HPLC. The pharmacokinetic parameters were computed by software program
      3P97. RESULTS: The lag time, the release behavior and the amount of VH from VH
      COERP within 24 hours were not influenced by the pH of dissolution medium and
      post-process, but obviously influenced by the different kinds of added material
      in swelling layer and the coating level of the inner swelling layer and the outer
      controlled layer. In vitro the lag time of release profile of VH from VH-COERP
      was 5 h and then VH was extended release from VH-COERP in the following time.
      Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax
      was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.
      CONCLUSION: The release profile of VH from VH-COERP was shown to be extended
      release after an conspicuous lag time in vitro and in vivo. So the drug can be
      taken by the patient before bed time and begin to work at the morning.

PMID- 17039786
TI  - [Effects of D-limonene and L-limonene on transdermal absorption of ligustrazine
      hydrochloride].
AB  - AIM: To investigate the effects and permeation mechanism of D-limonene and L
      limonene on transdermal delivery of ligustrazine hydrochloride (LH). METHODS:
      Transdermal flux of LH through porcine skin was determined in vitro by Franz-type
      diffusion cells. The peak shift and peak areas of C-H stretching vibration
      absorption were estimated by Fourier transform-infrared (FTIR). Morphological
      changes in the stratum corneum (SC) treated with enhancers were observed by a
      scanning electron microscope (SEM) and apparent density, a new concept, was
      proposed to estimate the desquamated extent of SC for the first time. RESULTS:
      There were no statistic difference (P > 0.05) between the transdermal fluxs of
      the enantiomer enhancers which were higher than those of control and azone. But
      the lag time of L-limonene was 2.55 times than that of D-limonene. The FTIR
      results revealed that the shift and decreased peak area of C-H stretching
      vibrations in the SC lipids were dependent on the enhancers. The enantiomers
      permeation enhancers, D-limonene and L-limonene, were able to perturb and extract
      the SC lipids to different extent. The disordering and extracting lipids activity
      of L-limonene was stronger than that of D-limonene. SEM studies demonstrated that
      the extraction of lipids was depended on the selected penetration promoters.
      CONCLUSION: D-limonene was the most effective enhancer which had the greater
      transdermal flux of LH and the least lag time. The results showed that the
      permeation enhancement mechanism of the enantiomer enhancers to LH was multiple
      ones including disordering and extracting the SC lipids and probably including
      stereoselective mechanism.

PMID- 17039787
TI  - [Pharmacokinetics of doxorubicin alginate microspheres and evaluation of its
      hepatic arterial embolization in vivo].
AB  - AIM: To investigate the pharmacokinetics of doxorubicin alginate microspheres
      (DOX-AM) in vivo after hepatic arterial embolization. METHODS: China miniature
      pigs were chosen as the experimental animals. Transcatheter hepatic arterial
      chemoembolization (TACE) with DOX-AM (experimental group), lipiodol and DOX (DOX
      lipiodol, control group 1), and infusion with DOX (control group 2) were
      performed after angiography and superselection of an intrahepatic branch of
      hepatic artery. After chemoembolization or infusion, the blood was collected at
      different time intervals. Drug concentration in plasma was measured by HLPC and
      the parameters of pharmacokinetics were calculated. RESULTS: The values of T1/2,
      AUC, Cmax, and MRT of the DOX-AM were significantly different from those of
      control group 1 and control group 2. After embolization, the DOX-AM embolized in
      the vessel and still retained there at 8 weeks. The digital subtraction
      arteriography (DSA) and computerized tomography (CT) showed the reliable
      embolization results. The histological examination indicated that the liver
      damnifications were changed transitorily in all groups (P < 0.05) and were
      recovered within two weeks. The liver damnifications increased in following
      order: DOX < DOX-AM < DOX-lipiodol. CONCLUSION: DOX-AM showed definite property
      of delayed release of drug in liver, and increased the retention time and
      concentration of DOX after embolization in vivo.

PMID- 17039788
TI  - [In vitro and in vivo assesemet of sodium norcantharidin lipid microsphere].
AB  - AIM: To prepare lipid microsphere of sodium norcantharidin (NCTD) and then study
      their characters and pharmacokinetic behavior. METHODS: Dynamic Light Scattering,
      HPLC and retrodialysis technique were used to determine the in vitro characters
      of the NCTD loaded lipid microsphere (LM), such as the particle size, xi
      potential, content, incorporation ratio, release profile and changes after
      dilute. And the plasma concentration was determined by HPLC-MS, compared with
      NCTD aqueous solution at the same time. RESULTS: Every property showed that the
      LM was preferable. The average diameter was about 200 nm. The xi-potential was -
      38 mV. The content was close to 100%. And the incorporation ratio exceeded 80%.
      After i. v. administration of single dose, the pharmacodynamic parameter of LM
      AUC was 111.28 microg x mL(-1) x h(-1). The data of plasma concentrations showed
      that the NCTD LM was of two compartment. There was no obvious difference between
      in vivo parameters of LM and reference solution. CONCLUSION: The NCTD LM was
      eligible and the character of it in vivo was not changed.

PMID- 17039789
TI  - [Excretion of (-)-clausenamide in rats].
AB  - AIM: To study the excretion of (-)-clausenamide in rats. METHODS: The urine,
      feces and bile were collected at predetermined time points after (-)-clausenamide
      was orally administrated to 6 rats (30 mg x kg(-1)). The concentrations of (-)
      clausenamide and its metabolite 6-OH-(-)-clausnamide were determined by HPLC
      MS/MS method using glipzide as the internal reference, and the accumulative
      excretion amount of (-)-clausenamide and 6-OH-(-)-clausenamide was calculated in
      the urine, feces and bile, separately. RESULTS: (-)-Clausenamide was recovered
      mostly (44%) from feces in 112 hours, 7.1% was found from urine in 120 hours and
      0.013% was detected from bile in 24 hours. The accumulative excretions of 6-OH-(
      )-clausenamide were 0.92% , 0.46% and 0.0003% of the administered dose from
      feces, urine and bile, respectively. CONCLUSION: The major amount of (-)
      clausenamide was recovered from feces after (-)-clausenamide was orally
      administrated to rats (30 mg kg(-1)).

PMID- 17039790
TI  - [Determination of three constituents in Radix Astragali by HPLC-MS].
AB  - AIM: To determine calycosin-7-O-beta-D-glucoside, astragaloside IV and
      formononetin in Radix Astragali and other relative samples by HPLC-MS. METHODS:
      HPLC was carried out with Agilent 1100LC/MSD, equipped with Agilent Zorbax SB C18
      column (250 mm x 4.6 mm ID, 5 microm) and mass spectrum detector. The mobile
      phase (CH3CN-H2O) was eluted in gradient mode. RESULTS: The calibration curves of
      calycosin-7-O-beta-D-glucoside, astragaloside IV and formononetin were linear in
      the range of 0.03 - 1.21 microg x mL(-1), 0.35 - 13.86 microg x mL(-1) and 0.38 -
      15.22 microg x mL(-1), respectively. These recoveries of samples were from 95% to
      105% with RSD less than 1.5%. CONCLUSION: The method was employed to analyse 25
      samples of Radix Astragali and other relative samples, including Radix Astragali
      slice, Radix Astragali Preparata, Hedysarum polybotrys Hand. -Mazz, Astragalus
      ernestii Comb. The contents of three constituents vary greatly because of the
      species, place of collection and season of harvesting. This method could apply to
      evaluate the quality of Radix Astragali and it is simple, sensitive and reliable.

PMID- 17039791
TI  - [Antitumor effects of nobiletin on Heps and its mechanism].
AB  - AIM: To study the inhibitory effect and mechanism of nobiletin on Heps tumor
      bearing mice. METHODS: Models of Heps tumor bearing mice were established. The
      inhibitory rates of tumor growth were calculated, the apoptosis morphology of
      tumor tissue was observed. The T lymphocyte transformation capacity was tested by
      MTT assay, the TNFalpha and IL-2 production were measured by LDH kits. RESULTS:
      Nobiletin could significantly inhibit Heps tumor growth. The inhibitory rates
      were 42.14% - 65.09% (P < 0.01). The morphology of tumor tissues in nobiletin
      group had typical characters of necrosis and apoptosis through transmission
      electron microscope. Nobiletin could stimulate T lymphocyte transformation and
      the production of TNFalpha and IL-2. CONCLUSION: Nobiletin has obvious antitumor
      effect on Heps, the main mechanism is to enhance the cellular immune function and
      induce apoptosis of tumor tissue.

PMID- 17039793
TI  - [Some usual definitions in the article of the middle ear surgery].

PMID- 17039792
TI  - [Recognition of chronic otitis media and mastoiditis].

PMID- 17039794
TI  - [Relationship between the content of fibrinogen in middle ear effusion and the
      effect of treatment on secretory otitis media].
AB  - OBJECTIVE: To study the relationship between the fibrinogen content in middle ear
      effusion (MEE) and the protracted inflammation of secretory otitis media (SOM)
      and to explore the possible mechanism of batroxobin in treatment of SOM. METHODS:
      The fibrinogen content of middle ear effusion from 156 patients with SOM was
      investigated with concretion technique at different stages. After two times
      punctuation of tympanum, the recurrence patients were randomly divided into two
      groups: batroxobin and dexamethasone group, and 0.5 ml (2 BU/ml) batroxobin or
      dexamethasone (2 mg/ml) was injected into middle ear cavity. The therapeutic
      effects were investigated. RESULTS: The concentration of fibrinogen in the
      recurrence group of SOM patients was higher than that in the cured group, and
      even higher in the second recurrence group than in the first recurrence group (P
      < 0.01). There was significantly different (P < 0.001) in the therapeutic
      efficacy between the batroxobin group (91.6%) and the dexamethasone group (62.
      5%); the difference of the fibrinogen content in MEE and air conduction of pure
      tone audiometry at frequencies (0.5, 1.0, 2.0 kHz) between the two groups after
      treatment were also significant (P < 0.01). CONCLUSIONS: Fibrinogen may play a
      significant role in the occurrence and development of secretory otitis media.
      Batroxobin had better therapeutic effect on SOM than dexamethasone. The mechanism
      of batroxobin in the treatment of SOM may be that the batroxobin can relief the
      depressant effect of fibrinogen on surface active agents of the Eustachian tube
      and prevent the fibrinogen from turning into insoluble fibrin polymer by means of
      fibrinolysis.

PMID- 17039795
TI  - [Preparation of new protein carrier of vaccine against pneumococcal otitis media
      with genetic engineering technology].
AB  - OBJECTIVE: To prepare pneumolysin as a new protein carrier of vaccine against
      otitis media with genetic engineering technology and establish the base of the
      study on pneumococcal conjugative vaccines. METHODS: Genomic DNA was isolated
      from streptococcus pneumoniae. A pair of primers which included two restriction
      sites was designed based on the published pneumolysin gene sequence. The
      pneumolysin gene was amplified from pneumococcal DNA with PCR technology. The
      restriction enzyme digested fragment was linked into the cloning vector PET-28a
      and the recombinant plasmid DNA containing pneumolysin was then transfected into
      host cell E. coli JM109 (DE3). RESULTS: DNA fragments were subcloned to construct
      the complete pneumolysin gene by a conventional coning and PCR. The inserted
      pneumolysin gene sequence was confirmed by DNA sequencing and the pneumolysin
      protein was successfully expressed. The relative molecular mass of the expressed
      product was 52 000. The expressed product amounted to 8% of the total host cell
      protein. CONCLUSIONS: The pneumolysin gene was successfully cloned into host cell
      using genetic engineering technology. The recombinant pneumolysin was expressed
      and purified for preparation. This work laid a foundation of the preparation of
      pneumococcal conjugative vaccines.

PMID- 17039796
TI  - [Immunohistochemical discrimination of aggressivity between the cholesteatoma
      from different positions].
AB  - OBJECTIVE: To investigate whether the cholesteatoma from different positions have
      different biological characteristics. METHODS: The expression of the Ki-67 and
      collagen IV in 19 specimens of cholesteatoma were stained immunohistochemically
      using the SP method, according to the origin of the specimens, include 7 cases
      from the epitympanum, 8 cases from tympanic sinus and 4 cases from the out
      acoustic canal. According to the severity of the inflammation in the perimatrix,
      the inflammation group included 7 cases, the non-inflammation group included 8
      cases. RESULTS: The average count was the same between the cholesteatoma from
      epitympanum and tympanic sinus. And the count of the cholesteatoma in the middle
      ear was also the same to the cholesteatoma from the out acoustic canal. But even
      from the same sample, the cholesteatoma from the positions with severe
      inflammation in the perimatrix count much higher, and the difference was
      statistically significant. Collagen IV had been found to localized in the basic
      membrane. In some specimens the staining of the collagen IV was not continuous.
      CONCLUSIONS: The results suggested that it was the severity of inflammation in
      the perimatrix influenced the differences, but not the origins of the
      cholesteatoma.

PMID- 17039797
TI  - [Endoscopic surgery for nasopharyngeal angiofibroma].
AB  - OBJECTIVE: To investigate the efficacy and the surgical techniques of transnasal
      endoscopic procedure for juvenile nasopharyngeal angiofibroma (JNA). METHODS:
      Twenty-one nasopharyngeal angiofibroma patients were treated using transnasal
      endoscopic approach. They were divided into group A (without intracranial
      extension) and group B (minimal intracranial extension) according to the staging
      of Sessions. The patients were treated mostly with endoscopic surgery. In two
      midfacial operations cases, endoscopy was also used. The staging, average blood
      loss during surgery, tumor residual, and (or) recurrent tumor were evaluated.
      RESULTS: Group A (19 cases) had an average blood loss of 1000 ml. Nineteen
      patients had no residual or recurrent tumor over a follow-up of 8-24 months.
      Group B (2 cases) had an average blood loss of 1500 ml. One of the patients had
      minimal residual tumor around the cavernous sinus, but showed no progression over
      a follow-up of 2 years. Another patient had no residual or recurrent tumor over a
      follow-up of 8 months. CONCLUSIONS: The data suggests that transnasal endoscopic
      surgical techniques can be used to treat JNA which either limited to nasal and
      nasopharyngeal cavities or and the tumor with sphenoid and ethmoid invasions and
      even minimal intracranial extension.

PMID- 17039798
TI  - [Effects of ephedrine on human nasal cilia movement measured with high-speed
      digital microscopy].
AB  - OBJECTIVE: To investigate the effects of ephedrine on human nasal cilia movement.
      METHODS: Ciliary beat frequency (CBF) of cultured human nasal epithelial cells
      was measured by high-speed digital microscopy in HBSS and ephedrine solution of
      different concentrations in 10 minutes. RESULTS: CBF of cultured nasal epithelial
      cells exposed to HBSS showed no significant changes in 10 minutes. However, in
      2.5 g/L , 5 g/L, 10 g/L and 20 g/L ephedrine solution, CBF increased
      significantly in 1-2 minutes and reached the apex, then it decreased gradually,
      at the 10th minute. CBF of the samples exposed to 2.5 g/L and 5 g/L ephedrine
      solution were slower than those in HBSS, but no significant changes were found.
      However, in 10 g/L and 20 g/L ephedrine solution, CBF decreased significantly
      when compared with samples in sHBSS. With the concentrations from 2.5 g/L to 20
      g/L ephedrine, the increment was independent on the concentration, the inhibitory
      effect was dependent on the concentration. CONCLUSIONS: In initial time, 2. 5 g/L
      20 g/L ephedrine stimulated CBF, then 10 g/L-20 g/L ephedrine inhibited CBF. The
      stimulation of 2.5 g/L and 5 g/L ephedrine on CBF was longer than that of 10 g/L
      and 20 g/L ephedrine. 5 g/L ephedrine had maximum stimulatory effect without
      obvious inhibitory effect on cultured human nasal CBF.

PMID- 17039800
TI  - [Autologous transplantation of fascia into the vocal fold for sulcus vocalis].
AB  - OBJECTIVE: To evaluate the effects of vocal fold autologous fascia
      transplantation for treating sulcus vocalis. METHODS: Sulcus vocalis among 23
      cases were dissected and vocal fold autologous fascia transplantation performed.
      For type III sulcus associated with thyroarytenoid muscle atrophy, autologous fat
      injection was carried out also. The voice acoustic quality and video
      laryngostroboscopic data were evaluated before and after surgery. RESULTS: Among
      23 patients, 4 were excluded from the analysis because of failure of surgery or
      lost to follow-up, leaving a total of 19 patients who were included in the
      analysis. Until 6-8 weeks after surgery, patients could start to phonate. Vocal
      quality became better 3 months postoperatively. Vocal quality became steady 6
      months after the surgery. Vocal improvement was obtained in 89. 5% (17/19) of the
      patients. The shapes, glottal closures and mucosal waves of vocal folds were
      improved. There was a significant decrease (improvement) in scales of grading,
      roughness, breathiness, and asthenic after surgery (P < 0.05). For the grade
      parameter, it improved 2 scales in 2 patients (10.5%) and 1 scale in 15 patients
      (79.0%). Acoustic analysis and maximum phonation time (MPT) were significantly
      improved after surgery (P < 0.01). Acoustic parameters of 42.0% (8/19) patients
      returned to normal range. MPT of 17 patients (89.5%) was in normal scopes. With 6
      to 24 months follow-up, vocal function was steadily. There was no apparent
      reabsorption. CONCLUSIONS: Autologous transplantation of fascia into the vocal
      fold was a useful and safe procedure for pathological sulcus vocalis.

PMID- 17039799
TI  - [Free anterolateral thigh flap for repairing the defects of oral cavity and
      maxillofacial].
AB  - OBJECTIVE: To investigate the outcomes following the tumor resection of oral
      cavity and maxillofacial and reconstruction with free anterolateral thigh flaps
      (ALT). METHODS: Thirty one patients underwent ALT reconstruction following the
      tumor resection from Dec. 2004 to Dec. 2005. Among them, 17 cases were squamous
      cell carcinoma (SCC) of tongue, 6 cases of buccal SCC and 8 other malignant. The
      size of the ALT flaps ranged from 4 to 8 cm in width and 6 to 23 cm in length.
      Tracheotomy were performed for 4 cases intraoperatively. RESULTS: The overall
      successful rate was 96.8%. Thirty cases survival no cancer, 1 case died of
      recurrent and no-controlled of lymph-node in 8 months after operation.
      Postoperative vessel thrombosis occurred in 3 flaps between 12 hours to 4 days
      after operation. Two of them were saved. The necrosis area of the third flap was
      25%. CONCLUSIONS: The ALT was benefit to repair the defects of oral cavity and
      maxillofacial, and the donor place was more easily hidden and didn't not
      influence the outlook and function; the important normal functional framing such
      as teeth and bone should be preserved; the pedicle of vessel could't be twisted
      during the procedure of reconstruction to avoid vein oppressed; the size of flap
      should be suitable to defects in order to avoid flaps being crowd and blood clot;
      tracheotomy was safe while repairing the defect of hard and soft palate.
      Reconstructive surgical procedures;

PMID- 17039801
TI  - [Surgical treatment of hyperthyroidism].
AB  - OBJECTIVE: In order to explore the management of peri-operation and the
      therapeutic effect in the surgical treatment of hyperthyroidism. METHODS: Fifty
      five cases of hyperthyroidism were undergone near-total thyroidectomy, during the
      operation recurrent laryngeal nerve was exposed, and the parathyroid was found
      with microscope when necessary. The third rank of inferior thyroid arteries were
      ligated to guarantee the blood supply for parathyroid. RESULTS: All cases
      underwent near-total thyroidectomy. There was no mortality, and no permanent
      recurrent laryngeal nerve palsy occurred, and no permanent hypoparathyroidism,
      and no recurrent hyperthyroidism. Follow-up was carried out 16 months to
      approximately 5 years after near-total thyroidectomy patients, Hypothyroidism
      occurred in 15 cases (57.7%), serum calcium levels were 2.15-2.45 mmol/L.
      CONCLUSIONS: Special attention should be given to the management of peri
      operation, the above the method can prevent operative complication in the
      surgical treatment of hyperthyroidism, with excellent result.

PMID- 17039802
TI  - [Distribution of cervical lymph node metastasis in well-differentiated thyroid
      carcinoma].
AB  - OBJECTIVE: To study the distribution of cervical lymph nodes metastases in
      patients with differentiated thyroid carcinoma, explore the surgical modality of
      the neck of cN + cervical node metastasis and evaluate the role of preoperative
      ultrasonography in detecting of cervical metastases of differentiated thyroid
      carcinoma. METHODS: Data were reviewed retrospectively from medical records
      between July 2003 and July 2005, in which 93 patients (113 sides) of
      differentiated thyroid carcinoma patients with cN + cervical lymph nodes
      metastasis. Patients were divided into 2 groups: group 1, 64 cervical sides with
      preoperative palpable cervical lymph nodes; group 2, 49 cervical sides with
      impalpable node but preoperative ultrasonic positive nodal metastasis. All the
      pathologic specimens were reviewed by pathologists counting the numbers of
      pathologic positive nodes and mapping localization of positive nodes in level II,
      III, IV, V and VI respectively. RESULTS: In 93 patients 21.5% (20/93) of those
      metastasize bilaterally. In those 113 sides specimens 92 sides (81.4%) involved
      multi-sites in the neck. The distribution of metastasized nodes were; level II,
      60.2% (68/113); level III, 70.8% (80/113); level IV,61.9% (70/113); level VI,
      58.4% (66/113); level V, 22.5% (25/113). The numbers of positive nodes of group 1
      were more than the number of group 2 (10.1 vs 6.9) and the involved levels of
      group 1 was also more than the levels of group 2 (3.18 level vs 2.61 level).
      Preoperative ultrasonography could detect 43.4% (49/113) of lymph nodes
      metastasis that were missed by palpation in the physical examination.
      CONCLUSIONS: The distribution of the cervical nodes in patients with
      differentiated thyroid carcinoma were multi-levels in the neck and mainly
      localized in level II , level III, level IV and level VI. Preoperative
      ultrasonography is a mainstay in detecting of cervical lymph nodes metastasis in
      thyroid cancer. For patients with differentiated thyroid carcinoma of cN +
      cervical lymph nodes should be undergone modified neck dissection, includes level
      II, III, IV, V, VI.

PMID- 17039803
TI  - [Experimental study on facial nerve regeneration by porous silk fibroin conduit].
AB  - OBJECTIVE: To evaluate the feasibility of using polyporus silk fibroin as a kind
      of novel material for facial nerve regeneration. METHODS: The porous silk fibroin
      conduit was used in the reconstruction of a 5 mm facial nerve gap of SD rat.
      Chitosan conduit was taken as control group. General observation,
      electrophysiological study, histological study and image analysis were performed
      2, 4, 6 and 8 weeks postoperatively. RESULTS: The facial nerve of SD rat
      regenerated successfully as time passed through. Mean CAP percentage of
      regenerated nerve in SF conduit was 24.94% +/- 5.73% 8 weeks postoperatively,
      which had no statistical significance with that of chitosan conduit group (P =
      1.125). And the average number of myelinated myelinated nerve fibers in SF
      conduit was 62. 5 +/- 6. 3, which had statistical significance with that in
      chitosan conduit group (P = 0.016). CONCLUSIONS: The porous silk fibroin conduit
      could effectively repair facial nerve defect and improve peripheral nerve
      functional recovery.

PMID- 17039804
TI  - [Effects of anti-cancer bioactive peptide on cell cycle in human nasopharyngeal
      carcinoma strain CNE].
AB  - OBJECTIVE: To investigate effects of two kinds of anti-cancer bioactive peptide
      (ACBP) on proliferation and cell cycle in human nasopharyngeal carcinoma strain
      CNE. METHODS: Cell culture was used in vitro, CNE cells were exposed to different
      concentration ACBP, in all groups, contrast groups were set up. And 24, 48, 72
      hours later, growth characteristics of CNE cells were studied by morphological
      observation and MTT assay . Cell cycle and apoptosis were analyzed by flow
      cytometry (FCM). RESULTS: In normal contrast group, CNE cells grew intensively
      and contacted with each other. However, cells which were treated with ACBP were
      inhibitory greatly in higher dose ACBP group, necrosis could be found. MTT assay
      showed that ACBP inhibited growth of CNE cell. FCM showed that ACBP (20.0
      microg/ml) could raise cell ratio of S phase and induce apoptosis of CNE cells.
      CNE cells were treated by two kind of ACBP (5.0 microg/ml) for 24 h, FCM showed
      that early apoptosis rate were (11.8 +/- 0.3)% and (8.1 +/- 0.2)% respectively,
      which showed statistical significance in comparison with control group (t =
      42.535, 47.300 respectively, P = 0.000). Under light microscope, some sings of
      cell apoptosis including coagulation of chromatin, fragmentation of nuclei and
      apoptotic body could be found. CONCLUSIONS: Two kinds of ACBP inhibited human
      nasopharyngeal carcinoma strain CNE proliferation and arrested the cells to S
      phase, also induced the cells to apoptosis. Nasopharyngeal neoplasms;

PMID- 17039805
TI  - [Apoptosis in nasopharyngeal carcinoma cell line NCE induced by curcumin and its
      molecular mechanism].
AB  - OBJECTIVE: To investigate the mechanism underlying the curcumin-induced apoptosis
      of nasopharyngeal carcinoma (NPC) cell line NCE cells. METHODS: The
      characteristics of apoptosis were identified by observation acridine orange and
      ethidium bromide stains, ultrastructure assay, DNA fragmentation assay and TdT
      mediated dUTP nick end labeling method (TUNEL). Mitochondrial membrane potential
      (delta psi m), activity of caspase-3, cytosol cytochrome C and expression of gene
      Fas were determined by flow cytometry (FCM), Western Blot and reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Several evidences of
      apoptosis were obtained from curcumin-treated NCE cells by acridine orange and
      ethidium bromide stains, ultrastructure identification, DNA fragmentation assay
      and TUNEL staining. And the mean TUNEL-positive rates increased significantly at
      the 3 different time points (12 h, 24 h and 48 h; 25.6%, 40.3% and 54.5%,
      respectively). In the curcumin-treated-groups, delta psi m altered significantly
      and the positive rates increased in a time-dependent manner. At the 3 different
      time points, the mean positive rates were 26.8%, 42.3% and 68.2%, respectively.
      When caspase-3 activity was detected, 80.5% cells presented proteases activities
      after 12 h incubation with curcumin. Western Blot analysis showed that
      cytoplasmic cytochrome C increased significantly after incubation with curcumin.
      Flow cytometry and RT-PCR analysis showed that curcumin could up-regulate the Fas
      expression in time-depended manner , the positive rates of Fas protein increased
      from 33.6% to 89.9%. CONCLUSIONS: Curcumin induced apoptosis of NCE cells both
      through mitochondria-dependent pathway and death receptor pathway.

PMID- 17039806
TI  - [Inhibitory effects of small interfering RNA specific to protein kinase CK2a on
      the growth of laryngeal carcinoma cells].
AB  - OBJECTIVE: To assess the effect of small interfering RNA (siRNA) specific to
      protein kinase CK2a on proliferation and apoptosis of Hep-2 cell line. METHODS:
      siRNA expression plasmid psiRNA-hH1neo-CK2 specific to protein kinase CK2a and
      non-specific siRNA expression plasmid psiRNA-hH1neo-cont were constructed
      respectively, and then were transfected into Hep-2 cells by lipofectamine
      methods. Protein kinase CK2a mRNA and protein of the transfected cells were
      detected by reverse transcription polymerase chain reaction (RT-PCR) and Western
      Blot, respectively. Proliferation and apoptosis of the transfected cells were
      observed by methyl thiazolyl tetrazolium (MTT) method and flow cytometry (FCM),
      respectively. RESULTS: Protein kinase CK2a mRNA and protein expressions were
      significantly decreased in the cells transfected with psiRNA-hH1neo-CK2 (P <
      0.05). The Hep-2 cells grew slowly after transfected with psiRNA-hH1neo-CK2(P <
      0.05). Obvious subdiploid peaks were found in the cells transfected with psiRNA
      hH1neo-CK2 (P < 0.05). CONCLUSIONS: siRNA expression plasmid specific to protein
      kinase CK2a suppressed the protein kinase CK2a expression and the proliferation
      of Hep-2, and induced apoptosis of Hep-2 cells.

PMID- 17039807
TI  - [A case of primary uvular carcinoma].

PMID- 17039808
TI  - [Relationship among lymphangiogenesis, vascular endothelial growth factor-C mRNA
      expression and cervical lymphatic metastasis in laryngeal carcinoma].

PMID- 17039809
TI  - [Expression of Glut-1 and Glut-3 in the head and neck squamous carcinoma].

PMID- 17039810
TI  - [Application of the transplanting amygdalas with pedicle in the surgery of
      pharynx].

PMID- 17039811
TI  - [Clinical diagnosis and therapy analysis of cervical lymphadenitis in cat-scratch
      disease].

PMID- 17039812
TI  - [Two cases report of the full resection of communicating cranio-osteoma in the
      adjacent skull to orbitonasal].

PMID- 17039813
TI  - [Pathology and classification of otitis media and early surgical treatment].

PMID- 17039814
TI  - [Diagnosis of otitis media with effusion in infants].

PMID- 17039815
TI  - [Preoperational evaluation of the feasibility of carotid artery resection for
      patients with head and neck neoplasm].

PMID- 17039816
TI  - [Correlated questions of tympanoplasty].

PMID- 17039817
TI  - Alternatives to traditional Medicare: Medicare Part C poised to prosper.
AB  - Recent events indicate that Medicare Part C (Medicare Advantage) plans are poised
      to prosper. Yet many employers express hesitation to offer Medicare Advantage,
      formerly known as Medicare+Choice, plans to their retirees because they are
      concerned about the potential withdrawal of those plans if there is a reversal of
      federal funding rules. This article addresses those concerns. It provides a
      historical overview of Medicare Part C and describes the impact of the most
      recent agency guidance. The author cites plan trends, raises employer
      implications and concludes that Medicare Advantage plans will continue to expand,
      possibly facilitated by employers as they implement leading-edge retiree medical
      designs.

PMID- 17039818
TI  - What comes after the retiree drug subsidy?
AB  - Under the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of
      2003 and agency guidance that has followed, an employer now faces many options,
      such as contracting with a supplemental prescription drug plan, offering its own
      prescription drug plan or eliminating its retiree drug subsidy. This article
      discusses the complex financial, administrative and communication issues an
      employer must ponder. For instance, short-term cash savings must be weighed
      against longer term accounting implications; yet the best financial alternative
      may come with other baggage that offsets the dollar savings. The author uses data
      to show what employers have done to date and raises unresolved issues employers
      must address as Medicare Part D evolves.

PMID- 17039819
TI  - Beyond the subsidy: Medicare Part D employer options.
AB  - The Medicare Modernization Act, now more than a year old, is opening up an array
      of possibilities for employers in dealing with retiree medical benefits. Many
      employers are beginning to look beyond the question of whether to accept
      Medicare's prescription drug subsidy and are more broadly considering how to
      shape their retiree health plans. This article describes the options available to
      employers now that Medicare Part D is in place. Through this analysis, the
      authors also explain how the choices employers make could affect retiree medical
      benefits and workforce planning issues.

PMID- 17039820
TI  - Evolving with Medicare: an approach to retirement strategy.
AB  - With Medicare Part D now providing prescription drug coverage, employers' retiree
      health plans are ripe for change. Effective change requires more than just
      adjustments. A global or enterprisewide approach to the development of a
      retirement strategy is important and should encompass five components: design,
      finance, administration, communication and control. This article discusses the
      strategic approach to crafting retiree health policy as the Medicare landscape
      continues to evolve.

PMID- 17039821
TI  - Health plans--eligibility decisions--preemption. DiFelice v. Aetna U.S.
      Healthcare.

PMID- 17039822
TI  - FMLA-serious health condition. Perry v. Jaguar of Troy.

PMID- 17039823
TI  - Child death review teams: a vital component of child protection.
AB  - The alarming number of children killed and seriously injured as a result of child
      maltreatment and neglect has led to increased calls for action. In response,
      interdisciplinary and multiagency child death review teams have emerged as an
      important component of child protection. Paradoxically, child death review teams
      are among the least visible and understood elements in efforts to protect
      children. This article examines the role and functions of child death review
      teams and their contributions to child welfare in practice, prevention, and
      policy.

PMID- 17039824
TI  - Indian Family Exception Doctrine: still losing children despite the Indian Child
      Welfare Act.
AB  - Since 1982, the Indian Family Exception Doctrine has been circumventing the
      Indian Child Welfare Act of 1978. Although not clearly defined, the doctrine has
      been pivotal in several American Indian child welfare cases in the United States.
      Over time, the doctrine continues to evolve and self-define. Several phrases have
      become part of the definition, such as Indian family and culture. This doctrine
      presents major concerns and implications in the field of child welfare.

PMID- 17039825
TI  - Comprehensive Family Services and customer satisfaction outcomes.
AB  - Comprehensive Family Services (CFS) is a strengths-based and partnership-oriented
      approach to casework implemented through multiple initiatives. This study
      examines the relationship between the practice of CFS and satisfaction of
      clients, foster parents, and community partners. CFS indicators are paired with
      statewide customer satisfaction survey results. CFS practices are associated with
      significantly higher customer satisfaction that improved over time for all
      groups. Although causality cannot be determined, the relationship is consistent,
      robust, and meaningful.

PMID- 17039826
TI  - The impact of state TANF policy decisions on kinship care providers.
AB  - Based on a survey of public assistance and child welfare agency staff, this
      article examines how state Temporary Assistance for Needy Families (TANF) policy
      decisions have affected kinship care providers. Findings indicate that most
      states have continued using TANF to provide income support to kinship caregivers,
      and some have used TANF to find related support services. These payments,
      however, are much lower than rates for licensed providers, and many kinship
      caregivers are subject to work, training requirements, and time limits.

PMID- 17039827
TI  - The relationship of severe acute respiratory syndrome coronavirus with avian and
      other coronaviruses.
AB  - In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV)
      emerged in humans in Guangdong Province, China, and caused an epidemic that had
      severe impact on public health, travel, and economic trade. Coronaviruses are
      worldwide in distribution, highly infectious, and extremely difficult to control
      because they have extensive genetic diversity, a short generation time, and a
      high mutation rate. They can cause respiratory, enteric, and in some cases
      hepatic and neurological diseases in a wide variety of animals and humans. An
      enormous, previously unrecognized reservoir of coronaviruses exists among
      animals. Because coronaviruses have been shown, both experimentally and in
      nature, to undergo genetic mutations and recombination at a rate similar to that
      of influenza viruses, it is not surprising that zoonosis and host switching that
      leads to epidemic diseases have occurred among coronaviruses. Analysis of
      coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal
      reservoir. Scientists examining coronavirus isolates from a variety of animals in
      and around Guangdong Province reported that SARS-CoV has similarities with many
      different coronaviruses including avian coronaviruses and SARS-CoV-like viruses
      from a variety of mammals found in live-animal markets. Although a SARS-like
      coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a
      lack of genomic sequences for the animal coronaviruses has prevented elucidation
      of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5'
      polymerase gene has a mammalian ancestry; whereas the 3' end structural genes
      (excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the
      host cell attachment viral surface protein, was shown to be a mosaic of feline
      coronavirus and avian coronavirus sequences resulting from a recombination event.
      Based on phylogenetic analysis designed to elucidate evolutionary links among
      viruses, SARS-CoV is believed to have branched from the modern Group 2
      coronaviruses, suggesting that it evolved relatively rapidly. This is significant
      because SARS-CoV is likely still circulating in an animal reservoir (or
      reservoirs) and has the potential to quickly emerge and cause a new epidemic.

PMID- 17039828
TI  - Increased level of Eimeria sensitivity to diclazuril after using a live coccidial
      vaccine.
AB  - Anticoccidial vaccine and an anticoccidial drug rotation program were compared to
      determine which program was more effective in producing coccidia populations
      sensitive of 1 ppm diclazuril. The study used an anticoccidial drug-sensitivity
      battery test (AST) to determine the baseline level of diclazuril sensitivity to
      field isolates of Eimeria spp. from seven broiler complexes that had used
      diclazuril. Based on percentage reduction in weight gain and lesion scores, 25%
      or fewer of the isolates were effectively controlled by diclazuril. Following the
      baseline sampling, four of the complexes switched to a nondiclazuril in-feed
      anticoccidial drug program and three of the complexes switched to a vaccination
      program for two broiler grow-out cycles as the sole coccidiosis-control program.
      This study demonstrated that the vaccine used (Coccivac-B) contained
      anticoccidial drug-sensitive strains. Eimeria isolates were subsequently
      collected from the identical houses and diclazuril AST results were compared with
      the baseline AST results. Following the two grow-out cycles, sensitivity of the
      isolates to diclazuril from the four complexes that continued to use in-feed
      anticoccidial drugs remained essentially unchanged. The isolates from the three
      complexes that switched to the vaccination program demonstrated a marked increase
      in diclazuril sensitivity, with 60%-100% of the isolates from each complex
      effectively controlled by diclazuril. Vaccination with the anticoccidial drug
      sensitive strains produced a measurable increase in the level of sensitivity to
      diclazuril.

PMID- 17039829
TI  - Development and evaluation of a DAS-ELISA for rapid detection of avian influenza
      viruses.
AB  - Rapid detection of avian influenza virus (AIV) infection is critical for control
      of avian influenza (AI) and for reducing the risk of pandemic human influenza. A
      double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was
      developed for this purpose. The method employed a monoclonal antibody (MAb) as
      the capture antibody and rabbit polyclonal IgG labeled with horseradish
      peroxidase as the detector antibody, and both antibodies were against type
      specific influenza A nucleoprotein (NP). The DAS-ELISA could detect minimally 2.5
      ng of influenza viral protein in virus preparations treated with Triton X-100,
      which is equvilent to 2.5 x 10(2) EID50 virus particles. This DAS-ELISA could
      detect all 15n AIV subtypes (H1-H15) and did not cross react with other avian
      pathogens tested. The DAS-ELISA were directly compared with virus isolation (VI)
      in embryonated chicken eggs, the current standard of influenza virus detection,
      for 805 chicken samples. The DAS-ELISA results correlated with VI results for
      98.6% of these samples, indicating a sensitivity of 97.4% and specificity of
      100%. The method was further tested with H5N1 and H9N2 AIV experimentally
      infected chickens, ducks, and pigeons, as well as field samples obtained from
      central China in 2005. The DAS-ELISA method has demonstrated application
      potential as an AIV screening tool and as a supplement for virus isolation in
      Asia.

PMID- 17039830
TI  - Characterization of monoclonal antibodies against fowl adenovirus serotype 1
      (FAV1) isolated from gizzard erosion.
AB  - Six clones of monoclonal antibodies (Mabs) to fowl adenovirus (FAV) serotype 1
      were produced. All Mabs reacted positively by enzyme-linked immunosorbent assay.
      Three Mabs recognized the putative 100-kD hexon protein and reacted to serotype 1
      specifically by western blot analysis but did not react to other FAV serotypes
      (2, 3, 4, 5, 6, 7, and 8a). These Mabs will be useful for immunodiagnosis of FAV
      serotype 1 infection in chickens with gizzard erosion and in further research
      studies involving the genomes and proteins of FAV serotype 1.

PMID- 17039831
TI  - Susceptibility and protection of naive and vaccinated racing pigeons (Columbia
      livia) against exotic Newcastle disease virus from the California 2002-2003
      outbreak.
AB  - The susceptibility, immune response, and protection to challenge after
      vaccination in racing pigeons (Columbia livia) was assessed with the 2002-2003
      exotic Newcastle disease (END) virus responsible for the most recent major
      outbreak in Southern California. Immunologically naive pigeons appeared resistant
      to disease, regardless of dose, after a natural route of exposure. Twenty percent
      morbidity was observed in each group of birds receiving between 10(2.1) and
      10(8.1) 50% embryo infectious dose (EID50) per bird, with one bird succumbing to
      challenge in the 10(8.1) EID50/bird group at day 12 postinoculation. Although
      resistant to disease, birds in all groups continued to shed virus from either
      oral or cloacal route at the end of the 14-day sampling period, and
      seroconversion was only observed in birds receiving > or =10(6.1) EID50. Single
      or double vaccination of juvenile and adult birds with pigeon paramyxovirus virus
      type 1 (PPMV-1) vaccine followed by END challenge with 10(6.1) EID50/bird
      decreased the duration, incidence, and viral load. A positive correlation was
      observed between the presence of hemagglutination-inhibiting antibody titers at
      challenge and decreased viral shedding. Overt clinical signs of disease were not
      observed in any PPMV-1-vaccinated birds after challenge.

PMID- 17039832
TI  - Susceptibility of various parental lines of commercial white leghorn layers to
      infection with a naturally occurring recombinant avian leukosis virus containing
      subgroup B envelope and subgroup J long terminal repeat.
AB  - Chickens from seven different parental lines of commercial White Leghorn layer
      flocks from three independent breeders were inoculated with a naturally occurring
      avian leukosis virus (ALV) containing an ALV-B envelope and an ALV-J long
      terminal repeat (LTR) termed ALV-B/J. Additional groups of chickens from the same
      seven parental lines were inoculated with ALV-B. Chickens were tested for ALV
      viremia and antibody at 0, 4, 8, 16, and 32 wk postinfection. Chickens from all
      parental lines studied were susceptible to infection with ALV-B with 40%-100% of
      inoculated chickens positive for ALV at hatch following embryo infection.
      Similarly, infection of egg layer flocks with the ALV-B/J recombinant virus at 8
      days of embryonation induced tolerance to ALV with 86%-100% of the chickens
      viremic, 40%-75% of the chickens shedding virus, and only 2/125 (2%) of the
      chickens producing serum-neutralizing antibodies against homologous ALV-B/J
      recombinant virus at 32 wk postinfection. In contrast, when infected with the ALV
      B/J recombinant virus at hatch, 33%-82% of the chickens were viremic, 28%-47%
      shed virus, and 0%-56% produced serum-neutralizing antibodies against homologous
      ALV-B/J recombinant virus at 32 wk postinfection. Infection with the ALV-B/J
      recombinant virus at embryonation and at hatch induced predominately lymphoid
      leukosis (LL), along with other common ALV neoplasms, including erythroblastosis,
      osteopetrosis, nephroblastomas, and rhabdosarcomas. No incidence of myeloid
      leukosis (ML) was observed in any of the commercial White Leghorn egg layer
      flocks infected with ALV-B/J in the present study. Data suggest that the parental
      line of commercial layers may influence development of ALV-B/J-induced viremia
      and antibody, but not tumor type. Differences in type of tumors noted in the
      present study and those noted in the field case where the ALV-B/J was first
      isolated may be attributed to differences in the genetics of the commercial layer
      flock in which ML was first diagnosed and the present commercial layer flocks
      tested in the present study.

PMID- 17039833
TI  - Detection and sequence analysis of avian polyomavirus and psittacine beak and
      feather disease virus from psittacine birds in Taiwan.
AB  - Avian polyomavirus (APV) and psittacine beak and feather disease virus (PBFDV)
      are the most common viral diseases of psittacine birds. In Taiwan, however, the
      existence of these viruses in psittacine birds has not been established.
      Polymerase chain reaction (PCR) methodology was therefore employed to ascertain
      whether APV and PBFDV genomes were present in isolates from psittacine birds of
      Taiwan. A total of 165 psittacine birds belonging to 22 genera were examined
      between 2002 and 2005. Findings revealed an APV-positive rate of 15.2%, a PBFDV
      positive rate of 41.2%, and an APV/PBFDV dual infection rate of 10.3%. After
      cloning and sequencing, sequences of the PCR products were compared with
      sequences obtained from GenBank. For APV, the nucleotide identity among VP1 and
      t/T antigen coding regions ranged from 97.5% to 100% and 97.6% to 100%,
      respectively. For PBFDV, the nucleotide identity of ORF V1 and ORF C1 sequences
      ranged from 92.2% to 100% and 83.3% to 100%, respectively. The derived amino acid
      sequence alignment for PBFDV ORF V1 fragments revealed the conservation of two
      replication motifs and of the nucleotide binding site motif. In PBFDV, six of 42
      deduced positions in the ORF C1 amino acid sequence were considered
      hypervariable. The established phylogenetic trees based on the four genome
      fragments examined in this study did not allow the assignment of particular APV
      or PBFDV nucleotide sequences to distinct avian species.

PMID- 17039834
TI  - Susceptibility of adult chickens, with and without prior vaccination, to
      challenge with Marek's disease virus.
AB  - Marek's disease (MD) outbreaks can occur in previously healthy adult layer or
      breeder flocks. However, it is not clear whether such outbreaks are caused by
      recent challenge with highly virulent (vv and vv+) strains of MD virus (MDV; i.
      e., new infection hypothesis) or by exacerbation of an earlier MDV infection (i.
      e., old infection hypothesis). To discriminate between these hypotheses, adult
      White Leghorn chickens of laboratory strains or commercial crosses with or
      without prior vaccination or MDV exposure were challenged at 18-102 wk of age
      with highly virulent MDVs, and lesion responses were measured. Horizontal
      transmission was studied in one trial. Challenge of adult chickens, which were
      free from prior MDV vaccination or exposure, with highly virulent MDV strains
      induced transient paralysis or tumors in 60%-100% of 29 groups (mean = 91%), and
      horizontal spread of virus was detected. The magnitude of the response was
      similar to that induced by challenge at 3 wk of age. In contrast, comparable
      challenge of adult chickens, which had been vaccinated or exposed to MDV early in
      life, induced transient paralysis or tumors in 0%-6% of 12 groups (mean = 0. 5%),
      although some birds showed limited virologic evidence of infection and
      transmission of the virus to contacts. The MD responses were influenced by the
      virulence of the challenge virus strain, and to a lesser extent by virus dose and
      route of exposure. Strong inflammatory lesions were induced in the brain and
      nerves of adult specific pathogen-free (SPF) chickens at 9-15 days after
      infection. The low susceptibility of previously vaccinated and exposed groups to
      challenge at > or =18 wk of age suggests that late outbreaks of MD in commercial
      flocks are not likely a result of recent challenge alone and that additional
      factors could be involved.

PMID- 17039835
TI  - Effects of nonimmunized egg yolk powder-supplemented feed on Salmonella
      enteritidis prevention and elimination in broilers.
AB  - Chicken consumption is a newly identified risk factor in Salmonella enterica
      serovar Enteritidis (SE) infection in humans. SE is widely distributed in
      commercial chicken flocks and high levels of cecal carriage and shedding may lead
      to broiler meat contamination. In the present study, the preventive and
      eliminative effect of nonimmunized freeze-dried egg yolk powder (EYP) on SE in
      broilers was investigated. In the prevention trial, reduced SE counts were
      observed in liver (P < or = 0.05), cecal contents, and fecal shedding (P < or =
      0.05) in birds fed 10% or 5% EYP. Histological examination of cecal wall and
      cecal tonsils at 23 days postinfection indicated a lesser degree of intestinal
      pathology. In the elimination trial, a significantly lower (P < or = 0.05) number
      of SE reached the liver and spleen, and a reduction in cecal carriage and fecal
      shedding was observed. The histological changes in the cecal mucosa and cecal
      tonsils reflected an apparent inflammation and mucosal repair and also suggested
      that the infection had not completely resolved, confirming SE bacterial
      isolations in the cecal tissue. The present study indicates that supplementing
      the diets of broilers with 5% nonimmunized EYP, at the early stages of the
      growing period, reduces preharvest Salmonella load with a minimal degree of
      intestinal pathology.

PMID- 17039836
TI  - Persistence of immunity in commercial egg-laying hens following vaccination with
      a killed H6N2 avian influenza vaccine.
AB  - The California poultry industry experienced an outbreak of H6N2 avian influenza
      beginning in February 2000. The initial infections were detected in three
      commercial egg-laying flocks and a single noncommercial backyard flock but later
      spread to new premises. The vaccination of pullet flocks with a commercially
      prepared, killed autogenous vaccine prior to their placements on farms with
      infected or previously infected flocks was used as a part of the eradication
      programs for some multiage, commercial egg production farms. The purpose of this
      study was to follow three vaccinated flocks on two commercial farms to track the
      immune responses to vaccination. The antibody-mediated responses of the three
      flocks followed in this study were markedly different. One flock achieved 100%
      seroconversion at 12.5 wk of age, but by 32 wk of age, all of the hens were
      seronegative by agar gel immunodiffusion (AGID). In contrast, at 32 wk of age,
      flocks from the other farm (flocks 2A and 2B) were 95% and 72% seropositive by
      AGID, respectively. Of the differences that were identified between the
      vaccination protocols on the two farms, the distinction that could explain the
      level of disparity between responses is the delivery of the second dose of
      vaccine with a bacterin on the first farm, which may have interfered with the
      persistence of immunity in this flock. Hens from flocks 2A and 2B were
      experimentally challenged at 25 wk of age with H6N2 avian influenza virus. Hens
      from flock 2A did not transmit virus to naive contact-exposed hens, but hens from
      flock 2B did. At 34 wk of age, hens from flock 2A were again challenged and naive
      contact-exposed hens were infected in this second trial. These challenge
      experiments served to demonstrate that despite detectable antibody responses in
      flocks 2A and 2B, the birds were protected from infection for less than 21 wk
      after the second vaccination.

PMID- 17039837
TI  - Isolation and characterization of an adventitious avian leukosis virus isolated
      from commercial Marek's disease vaccines.
AB  - Commercial Marek's disease (MD) vaccines produced by two manufacturers were
      tested for possible contamination with avian leukosis virus (ALV). Samples of MD
      vaccines manufactured by two companies (A and B) were received from a breeder
      company; samples were also received directly from vaccine company B. Using virus
      isolation tests, samples initially tested positive for subgroup E (endogenous)
      ALV. However, upon repassage, the vaccines also tested positive for exogenous
      ALV. The isolated exogenous ALV proved to be a subgroup A virus, as determined by
      flow cytometry using polyclonal chicken antibodies specific for various subgroups
      of ALV, and by DNA sequencing of the envelope glygoprotein (gp85). The exogenous
      ALV isolated from MD vaccines was inoculated in chickens from ADOL lines 15I(5) x
      7(1) and 0 to determine its pathogenicity and compare it with that of Rous
      associated-virus-1 (RAV-1), the prototype strain of ALV-A. Each chicken from each
      line was inoculated with approximately 10,000 infectious units of RAV-1 or the
      ALV-A isolated from vaccines termed B-39 virus at 7th day of embryonation. At
      hatch, and at 4, 8, and 16 wk of age, chickens were tested for viremia and
      cloacal shedding; chickens were also observed for ALV-induced tumors within 16 wk
      of age. Viremia and cloacal shedding results suggest that chickens from both
      lines were susceptible to infection with either virus. Within 16 wk of age, the
      proportion of ALV tumors induced by strain B-39 in line 0 and line 15I5 x 7(1)
      chickens was 0% and 12%, respectively, compared with 62% and 67% in chickens
      inoculated with RAV-1. The data indicate that commercial MD vaccines produced by
      two manufacturers were contaminated with endogenous subgroup E and an exogenous
      subgroup A ALV. Further, data from biological characterization suggest that the
      ALV-A isolated from commercial MD vaccines is of low oncogenicity, compared with
      that of RAV-1. GenBank accession numbers: The gp85 gene sequences of ALV isolated
      from commercial Marek's disease vaccines have been deposited in GenBank and
      assigned the following accession numbers: A46 subgroup A, DQ412726 ; B53 subgroup
      A, DQ412727; A46 subgroup E, DQ412728; B53 subgroup E, DQ412729.

PMID- 17039838
TI  - Isolation, identification, and comparison of four isolates of avian paramyxovirus
      serotype 2 in China.
AB  - Four Yucaipa-like viruses of avian paramyxovirus serotype 2 (APMV-2) were
      isolated in China from the imported Gouldian Finch (Chloebia gouldiae) and
      broilers in 1998-2002, and were named F4, F6, F8, and NK, respectively. Examined
      under electron microscope, the isolates were found to be round in shape and
      varying in size. The results of the hemagglutination inhibition test and indirect
      enzyme-linked immunosorbent assay (using monoclonal antibodies) showed some
      differences between the isolates and the reference strain Yucaipa. The isolates
      derived from chickens had a closer relationship to Yucaipa virus than did those
      of finches. Sequence comparison of the fusion gene and the haemagglutinin
      neuraminidase gene showed similar results, although the variations were lesser
      among APMV-2 viruses in nucleotide and amino acid sequence. By sequence
      comparison, it was also revealed that at the molecular level the four virus
      strains belong to APMV-2, and that two of the strains were isolated from the same
      group of imported Gouldian Finches.

PMID- 17039839
TI  - Molecular analysis of infectious bursal disease virus from bursal tissues
      collected on FTA filter paper.
AB  - We investigated the feasibility of using FTA filter cards for the storage of
      bursas of Fabricius containing infectious bursal disease virus (IBDV) and for
      IBDV detection by reverse transcriptase (RT)-polymerase chain reaction (PCR), and
      characterization by restriction fragment length polymorphism (RFLP) or nucleotide
      sequencing. The FTA card is a cotton-based cellulose membrane containing
      lyophilized chemicals that lyses many types of bacteria and viruses. IBDV was
      inactivated upon contact with the FTA as shown by the inability of the virus to
      be propagated in embryonating chicken eggs. Viral RNA in minced bursas or stamped
      bursas could be amplified by RT-PCR (VP2 gene fragment, 248 base pairs) after
      storage on FTA for at least 15 days at room temperature or 8 mo at -20 C.
      Analytical sensitivity of the test was between 0.5-5 ng of RNA template or 5 x
      10(1) mean tissue culture infective dose (TCID50)/FTA spot. Detection rate of
      IBDV in domestic clinical samples collected on FTA or collected by the non-FTA
      standard procedure was 36.7% and 41.7%, respectively, which represents 88%
      agreement. Detection of IBDV from FTA cards inoculated with bursal tissues in the
      laboratory or in the field was 36.7% and 37.1%, respectively. Detection of IBDV
      from FTA samples when the cards were inoculated with bursal tissues and sent
      through customs into the United States was 32.9%. Analysis of the amplified
      products showed that molecular characterization of IBDV by RFLP or nucleotide
      sequencing is feasible in bursas stored on FTA at 25 C for 1-3 mo or at -20 C for
      at least 8 mo. The use of FTA for the collection of bursal tissues and
      simultaneous inactivation of IBDV allows the movement of specimens within the
      United States and also from outside the United States in compliance with federal
      regulations and in a manner adequate for molecular characterization.

PMID- 17039840
TI  - Molecular characterization and typing of chicken and turkey astroviruses
      circulating in the United States: implications for diagnostics.
AB  - Avian astroviruses were detected by reverse transcriptase and polymerase chain
      reaction in intestinal contents collected from commercial chickens and turkeys
      from throughout the United States from 2003 through 2005. Astroviruses were
      detected in birds from both healthy and poorly performing flocks with or without
      enteric disease. Phylogenetic analysis was performed with sequence data from the
      polymerase (ORF-1b) genes of 41 turkey-origin astroviruses and 23 chicken-origin
      astroviruses. All currently available avian astrovirus sequence data and selected
      mammalian astrovirus sequence data were included in the analysis. Four groups of
      avian astroviruses were observed by phylogenetic analysis: turkey astrovirus type
      1 (TAstV-1)-like viruses, turkey astrovirus type 2 (TAstV-2)-like viruses, both
      detected in turkeys; avian nephritis virus (ANV)-like viruses, detected in both
      chickens and turkeys; and a novel group of chicken-origin astroviruses (CAstV).
      Among these four groups, amino acid identity was between 50.1% and 73.8%, and was
      a maximum of 49.4% for all avian isolates when compared with the mammalian
      astroviruses. There were multiple phylogenetic subgroups within the TAstV-2, ANV,
      and CAstV groups based on 9% nucleotide sequence divergence. Phylogenetic
      analysis revealed no clear assortment by geographic region or isolation date.
      Furthermore, no correlation was observed between the detection of a particular
      astrovirus and the presence of enteric disease or poor performance. Based on
      these data, a revision of the present taxonomic classification for avian
      astroviruses within the genus Avastrovirus is warranted.

PMID- 17039841
TI  - Occurrence of pathogenicity island I(APEC-O1) genes among Escherichia coli
      implicated in avian colibacillosis.
AB  - Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a leading
      cause of economic loss to the poultry industry worldwide. The ability of APEC to
      cause disease is determined by certain virulence markers, some of which are
      located on pathogenicity islands (PAls). We recently described one such PAI in an
      APEC O1:K1 strain (APEC-O1). This PAI, termed PAI I(APEC-O1), carries the genes
      of the pap operon, a region similar to the tia invasion determinant of
      enterotoxigenic E coli; ireA, a gene that encodes an iron-responsive element; and
      a novel 1.5-kb region, ORF 54. Here, the occurrence of six selected loci of PAI
      I(APEC-O1) (papA, papC, papG, ireA, tia, and ORF 54) among APEC and fecal E. coli
      strains from apparently healthy chickens (avian commensal E. coli) was determined
      using polymerase chain reaction (PCR) techniques. None of the commensal E. coli
      was positive for all six traits, whereas 7.2% of the APEC isolates were positive
      for all the traits. Although there was no significant difference in the
      occurrence of ORF 54 among APEC and commensal E. coli, tia, ireA, papC, and papG
      genes were predominantly present in APEC rather than in avian commensal E. coli.
      papA was detected in only 6.3% of APEC, perhaps because of the presence of
      allelic variants of the gene. Additionally, the presence of all six traits was
      tested with PCR in APEC isolates collected in the 1980s, and these results were
      compared with those obtained with the APEC isolated in the 1990s. There was no
      significant difference in the occurrence of tia, ireA, papC, papG, and ORF 54
      between APEC isolates collected during the different decades. However, papA was
      more frequently present in APEC from the 1980s than it was in APEC from the
      1990s. Phylogenetic group of an isolate did not correlate with pathogenicity or
      the presence of PAI traits, except that more APEC of the low-pathogenicity group
      belonged to the phylogenetic group B1. However, PAI traits occurred more
      frequently in isolates belonging to the intermediate- and high-pathogenicity
      groups than in isolates of low pathogenicity.

PMID- 17039842
TI  - Detection of rotaviruses and intestinal lesions in broiler chicks from flocks
      with runting and stunting syndrome (RSS).
AB  - The intestinal tract and intestinal contents were collected from 34 stunted, 5-to
      14-day-old broiler chicks from eight flocks with runting and stunting syndrome
      (RSS) in Northern Germany to investigate intestinal lesions and the presence of
      enteric pathogens with a special focus on rotaviruses (RVs). Seven chicks from a
      healthy flock were used as controls. Severe villous atrophy was seen in chicks
      from six flocks with RSS but not in the control flock. Lesions were often
      "regionally" distributed in the middle-to-distal small intestine. Transmission
      electron microscopy (TEM), polyacrylamide-gel electrophoresis (PAGE), reverse
      transcriptase polymerase chain reaction (RT-PCR), and seminested RT-PCR were used
      for detection and characterization of RVs. The PAGE allows discrimination of
      different RV groups, and the RT-PCR was used to verify the presence of group (gp)
      A RVs. RVs were detected (by all methods) in 32 of 34 chicks from the flocks with
      RSS. By TEM (negative staining), RV particles were observed in intestinal
      contents of 28 chicks from the flocks with RSS. PAGE analysis showed four RV
      groups: gpA, gpD, gpF, and gpG. Group A RVs were detected in four chicks from two
      flocks with RSS, without intestinal lesions. GpD RVs were detected in 12 chicks
      of five flocks with RSS, 10 of them with severe villous atrophy. GpF RVs were
      confirmed in four chicks from three flocks with RSS and in two birds in the
      control flock. GpG RVs were verified in two chicks from two flocks with RSS, one
      with, and one without, intestinal lesions. At present, PCR methods are only
      available for detection of gpA RVs. Using RT-PCR, gpA RVs were identified in
      samples from 22 chicks including samples of two chicks from the control flock.
      Statistical analysis revealed a positive correlation between presence of gpD RV
      and severe villous atrophy in flocks with RSS. The results suggest that gpD RV
      plays a major role in the pathogenesis of RSS.

PMID- 17039843
TI  - Production and characterization of monoclonal antibodies that react to the
      nucleocapsid protein of avian metapneumovirus subtype C.
AB  - Monoclonal antibodies (MAbs) were prepared against avian metapneumovirus (aMPV)
      subtype C (aMPV/ Minnesota/turkey/1a/97). Six MAbs were selected based on enzyme
      linked immunosorbent assay activities and characterized by isotyping,
      neutralization test, western blot analysis, and immunohistochemistry assay. The
      results showed that three MAbs (3E, 9D, and 12C) belonged to the IgG1 subclass,
      whereas the other three (5D, 8E, and 16E) were of the IgG2a subclass. None of the
      six MAbs neutralized aMPV infectivity at a detectable level, but all reacted with
      both denatured and nondenatured forms of the nucleocapsid (N) protein of aMPV,
      suggesting that these MAbs may recognize structurally independent epitopes of the
      N protein. These MAbs provide new tools and methods for investigating aMPV
      infection and pathogenesis, as well as diagnosis of aMPV disease.

PMID- 17039844
TI  - Comparison of Salmonella enterica serovar enteritidis levels in crops of fed or
      fasted infected hens.
AB  - Long-term feed withdrawal has been shown to increase ileocecal intestinal
      colonization and fecal shedding of Salmonella enterica serovar Enteritidis in
      challenged hens. Less information is available regarding effects of fasting on
      crop colonization. Two trials were conducted to compare effects of 14-day feed
      withdrawal vs. full feed on crop colonization in hens challenged with Salmonella
      Enteritidis. The levels of Salmonella Enteritidis in the crops of fasted hens
      were significantly higher than in nonfasted hens on days 3 and 10 and days 3, 9,
      and 16 postinfection (PI) in trials 1 and 2, respectively. Fecal shedding of
      Salmonella Enteritidis was significantly increased in the fasted hens on day 10
      PI in trial 1. Analysis of crop IgA anti-Salmonella Enteritidis
      lipopolysaccharide levels in crop lavage samples of hens in trial 1 revealed a
      humoral response PI in both treatment groups with no significant differences,
      although peak response for fasted hens occurred 1 wk later. Histologic evaluation
      of hematoxylin and eosin-stained crop sections from trial 1 birds revealed mild
      to moderate heterophilic infiltration within the crop lamina propria (LP) or LP
      and epithelium of nonfasted infected hens at 24 and 96 hr PI. In comparison,
      heterophils in crops of fasted hens infected at this time point were sparse,
      indicating a possible diminished heterophil response in the fasted birds.
      Multifocal areas of tissue inflammation, as indicated by marked heterophil
      infiltration, with necrosis and sloughing of epithelium, were observed in crops
      from fasted hens at day 11 PI (14th day of feed withdrawal) but not in the fed
      groups. This severe heterophilic inflammation was observed in both challenged and
      nonchallenged fasted hens, suggesting that some factor other than Salmonella
      Enteritidis was responsible. These results indicate that feed withdrawal can have
      a dramatic effect on the integrity of the crop and its ultimate response to
      infection.

PMID- 17039845
TI  - Presence of inoculated Campylobacter and Salmonella in unabsorbed yolks of male
      breeders raised as broilers.
AB  - Day-old male broiler breeder chicks were obtained from a commercial hatchery and
      raised as broilers. For Experiment 1, at 5 wk of age, the broilers were orally
      inoculated with a 10(6) cfu/ml of a characterized strain of Campylobacter jejuni
      and a cocktail (three naladixic acid-resistant strains) of Salmonella serovars.
      One week after inoculation, the birds were euthanatized and defeathered. The
      abdominal cavity was examined and any unabsorbed yolk material (and remaining
      yolk stalk) and ceca were aseptically removed for microbiological analyses. For
      each pooled sample (two birds per pool), an aerobic plate count (APC), an
      Enterobacteriaceae (ENT) count, and a test for the presence of Campylobacter and
      Salmonella was performed. For Experiment 2, at 5 wk of age, the broilers were
      orally inoculated with 10(5) cfu/ml of a characterized strain of Campylobacter
      jejuni. One week after inoculation, the birds (n = 20) were killed, defeathered,
      and the yolk stalk, attached yolk, or free-floating yolk and ceca were
      individually analyzed for presence of Campylobacter. For Experiment 1, the
      Salmonella-inoculated birds had 2/12 ceca and 0/12 unabsorbed yolk samples
      positive for Salmonella. The average yolk APC was log10 3.4 cfu/g and the average
      ENT was log10 1.9 cfu/g. For the Campylobacter-inoculated birds, 12/12 ceca and
      9/12 unabsorbed yolk samples were positive for Campylobacter. The average yolk
      APC was log10 3.5 cfu/g and the average ENT was log10 3.1 cfu/g. For Experiment
      2, the inoculated Campylobacter birds had 19/20 ceca, 5/20 free floating yolks,
      and 19/20 yolk stalks positive. In Experiment 1, the inoculated Campylobacter
      colonized the ceca in every instance and were present in 75% of the unabsorbed
      yolks. Alternatively, the inoculated Salmonella were not found in any of the
      unabsorbed yolks and only rarely in the ceca. In Experiment 2, the inoculated
      Campylobacter was found in very high numbers in the yolk and internal body
      samples. Determining to what extent these internal bodies and unabsorbed yolks
      play in bacterial colonization and contamination of the birds at processing has
      not been determined. The next step will be to determine the incidence of
      unabsorbed yolks and presence of Campylobacter and Salmonella in these bodies of
      commercial broilers at processing.

PMID- 17039846
TI  - Higher incidence of Eimeria spp. field isolates sensitive for diclazuril and
      monensin associated with the use of live coccidiosis vaccination with paracox-5
      in broiler farms.
AB  - Twenty European Eimeria spp. field isolates were subjected to an anticoccidial
      sensitivity test (AST). The anticoccidial drugs tested were diclazuril (Clinacox)
      and monensin (Elancoban). The assay was performed in a battery cage trial.
      Infected medicated birds were compared with an unmedicated control group.
      Coccidial lesion scores and oocyst shedding were used as parameters. The results
      of the AST show that resistance is common amongst coccidiosis field isolates,
      especially Eimeria acervulina (68% and 53% resistance for diclazuril and
      monensin, respectively). Resistance is less frequent amongst Eimeria maxima (38%
      and 50% resistance for diclazuril and monensin, respectively) and Eimeria tenella
      isolates (23% and 38% resistance for diclazuril and monensin, respectively). A
      highly significant influence of the coccidiosis prevention program (live
      coccidiosis vaccination with Paracox-5 vs. anticoccidial drugs in feed) on the
      sensitivity patterns of Eimeria spp. field isolates for both diclazuril (P=
      0.000) and monensin (P= 0.001) was found. Further, when looking at the single
      species and each anticoccidial drug level, significantly more sensitivity of E.
      acervulina for monensin (P= 0.018), E. maxima for diclazuril (P = 0.009), and E.
      tenella for diclazuril (P = 0.007) was found in isolates originating from
      vaccinated flocks. Moreover, for E. acervulina and diclazuril, E. maxima and
      monensin, and E. tenella and monensin a trend toward higher sensitivity of
      isolates for these products was found when live coccidiosis vaccination was
      applied. The present study shows that sensitivity for the anticoccidial drugs
      diclazuril and monensin is more frequent in Eimeria spp. field isolates
      originating from broiler farms where a coccidiosis vaccination policy is
      followed.

PMID- 17039847
TI  - Isolation and molecular biological investigations of avian poxviruses from
      chickens, a turkey, and a pigeon in Croatia.
AB  - In the last 3 yr, several outbreaks of avian poxviruses (APVs) have been observed
      in different parts of Croatia. Four strains of APVs, from chickens, a pigeon, and
      a turkey, were isolated from cutaneous lesions by inoculation onto the
      chorioallantoic membranes (CAM) of 12-day-old specific-pathogen-free chicken
      embryos. The resulting proliferative CAM lesions contained eosinophilic
      cytoplasmic inclusion bodies. The characteristic viral particles of poxvirus were
      detected in the infected CAM and also in the infected tissues by transmission
      electron microscopy. Further identification and differentiation of the four
      various APVs were carried out by the use of a polymerase chain reaction (PCR)
      combined with restriction enzyme analysis. Using one primer set, which framed a
      region within the APV 4b core protein gene, it was possible to detect APV
      specific DNA from all four tested isolates. PCR results revealed no recognizable
      differences in size of amplified fragments between the different APVs from
      chickens, turkey, and pigeon. Restriction enzyme analysis of PCR products using
      NlaIII showed the same cleavage pattern for turkey and chicken isolates and a
      different one for the pigeon isolate. Multiplex PCR for direct detection of APV
      and reticuloendotheliosis virus (REV) was carried out to determine the possible
      integration of REV in the genome of isolated APVs. The obtained results revealed
      that REV was present in chicken and turkey strains of poxviruses, whereas the
      pigeon isolate was negative. It is not known whether the avipoxvirus vaccine
      strain used in Croatia is contaminated with REV or if the REV is naturally
      contaminating Croatian field strains of fowl poxvirus. The latter is indicated by
      the negative REV finding in the pigeon, which was not vaccinated. The results of
      the present study indicate the reemergence of fowlpox in Croatia, where
      infections have not been recorded since 1963 and never confirmed etiologically.

PMID- 17039848
TI  - Characterization of monoclonal antibodies to avian Escherichia coli Iss.
AB  - Colibacillosis accounts for annual multimillion dollar losses in the poultry
      industry, and control of this disease is hampered by limited understanding of the
      virulence mechanisms used by avian pathogenic Escherichia coli (APEC). Previous
      work in our laboratory has found that the presence of the increased serum
      survival gene (iss) is strongly associated with APEC but not commensal E. coli,
      making iss and the protein it encodes (Iss) candidate targets of colibacillosis
      control procedures. Previously, we produced monoclonal antibodies (MAbs) against
      Iss to be used as a reagent in studies of APEC virulence and colibacillosis
      pathogenesis. Unfortunately, the utility of these MAbs was limited because these
      MAbs exhibited nonspecific binding. It was thought that the lack of specificity
      might be related to the fact that these MAbs were of the immunoglobulin M (IgM)
      isotype. In the present study, new MAbs were produced using a different
      immunization strategy in an effort to generate MAbs of a different isotype. Also,
      because Iss bears strong similarity to Bor, a lambda-derived protein that occurs
      commonly among E. coli, MAbs were assessed for their ability to distinguish Iss
      and Bor. For these studies, the bor gene from an APEC isolate was cloned into an
      expression vector. The fusion protein expressed from this construct was used to
      assess the potential of the anti-Iss MAbs produced in the past and present
      studies to distinguish Bor and Iss. The MAbs produced in this study were of the
      IgG1 isotype, which appeared to bind more specifically to Iss than previously
      generated antibodies in certain immunologic procedures. These results suggested
      that the MAbs generated in this study might prove superior to the previous MAbs
      as a reagent for study of APEC. However, both MAbs recognized recombinant Iss and
      Bor, suggesting that any results obtained using anti-Iss MAbs would need to be
      interpreted with this cross-reactivity in mind.

PMID- 17039849
TI  - Natural presence of Campylobacter spp. in various internal organs of commercial
      broiler breeder hens.
AB  - Campylobacter are known to cause acute bacterial gastroenteritis in humans.
      Poultry products have been implicated as a significant source of these
      infections. Six experiments were performed to determine whether Campylobacter
      could be isolated naturally from the primary and secondary lymphoid organs,
      liver/gallbladder, and ceca of commercial broiler breeder hens. Broiler breeder
      hens were acquired from different commercial sources during the early, middle,
      and late lay cycles. The birds were euthanatized, defeathered, and aseptically
      opened. To reduce the possibility of cross-contamination between samples, the
      thymus, spleen, and liver/gallbladder were aseptically removed prior to removal
      of the ceca. Individual samples were placed in sterile bags, packed on ice, and
      transported to the laboratory for evaluation. In this study Campylobacter were
      found in 11 of 43 thymii, eight of 43 spleens, four of 43 liver/gallbladders, and
      30 of 43 ceca. Overall, 28 of 53 isolates from the above samples were
      Campylobacter coli and 25 of 53 isolates were found to be Campylobacter jejuni.

PMID- 17039850
TI  - Passive West Nile virus antibody transfer from maternal Eastern screech-owls
      (Megascops asio) to progeny.
AB  - Transovarial antibody transfer in owls has not been demonstrated for West Nile
      virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern
      Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal
      antibody transfer, as well as titers and duration of maternal antibodies. Twenty
      four owlets aged 1 to 27 days old circulated detectable antibodies with
      neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating
      that WNV antibodies are passively transferred transovarially is important for
      accurate interpretation of serologic data from young birds.

PMID- 17039851
TI  - West Nile virus-associated mortality events in domestic Chukar partridges
      (Alectoris chukar) and domestic Impeyan pheasants (Lophophorus impeyanus).
AB  - West Nile virus (WNV) infection was diagnosed in captive juvenile chukars
      (Alectoris chukar), and captive juvenile Impeyan pheasants (Lophophorus
      impeyanus) on the basis of necropsy, histopathology, polymerase chain reaction,
      and immunohistochemistry. The chukars were kept in a game bird farm that
      experienced two outbreaks with approximately 25% mortality in hundreds of chukars
      between September and October 2002 and during the same months in 2003. The
      submitted pheasants were part of a group of 15 juvenile Impeyan pheasants that
      all died within approximately 2 wk at the end of August 2002. The macroscopic
      lesions in the pheasants were dominated by mucosal hemorrhage at the
      proventricular to ventricular junction and cecal ulcers, whereas the gross
      lesions in the chukar partridges were nonspecific. The predominant microscopic
      lesion in the chukar partridges was myocardial necrosis, whereas fibrinous and
      necrotizing splenitis was prominent in the pheasants. Viral antigen was usually
      widespread in animals of both species. Spontaneously occurring WNV infection
      should be considered a differential diagnosis in cases of mortality among select
      species of galliform birds.

PMID- 17039852
TI  - Litter impaction of the lower intestinal tract in male broiler breeders.
AB  - Increased mortality occurred among males in a house of 26-wk-old broiler
      breeders. A severe impaction of the lower intestinal tract, because of litter,
      was found on necropsy in two of three recently dead cockerels. Litter could be
      seen in the markedly distended vent of the most affected bird. This bird also had
      feces and litter in the body cavity because of a ruptured small intestine. Both
      birds had extensive urate and fecal soiling of feathers around the vent. Other
      visceral organs were normal except for lack of fat around the base of the heart
      and decreased myocardial tone. Impaction of the lower intestinal tract in these
      birds most likely resulted from eating litter because of a change in feeding
      regimen, which caused confusion and feed competition among male birds.

PMID- 17039853
TI  - Predation as a cause of neurologic signs and acute mortality in a pheasant flock.
AB  - A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was
      evaluated for a sudden increase in mortality and acute neurological signs after
      having been previously diagnosed 3 wk earlier with a chronic respiratory disease
      of undetermined etiology. Approximately 25 live birds were displaying
      neurological signs including circling, ataxia, and obtunded behavior and 50 birds
      were dead. Three birds with neurological signs were submitted for evaluation.
      Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds
      through the skull and into the brain were found. Trauma from a wild predatory
      mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the
      pheasant house and expressed surplus killing behavior was determined to be the
      cause of the acute neurological signs and mortality. The relationship of the
      chronic respiratory disease to the predation episode was not determined but it is
      possible that pheasants with severe respiratory disease may have had increased
      susceptibility to predation.

PMID- 17039854
TI  - Micronutrients in women's reproductive health: I. Vitamins.
AB  - Proper nutritional status of women before, during, and after pregnancy is an
      important element of reproductive health. It maintains maternal health and
      reduces the risk of adverse pregnancy outcome, birth defects and chronic disease
      in children later in postnatal life. Pregnancy creates a special metabolic demand
      for high-quality nutrients. With careful food selection, it is possible to obtain
      most of the recommended levels of nutrients. Apart from the dietary intake,
      nutrition is highly dependant on economic status, social and cultural
      environment, and personal habits of the mother. Nutritional imbalance could cause
      detrimental effects to the pregnant woman, influence pregnancy outcome, and
      impair breast milk composition. Despite the extensive research, we still do not
      have a complete understanding how nutritional status of the mother influences her
      health as well as fetal growth and development. It is well known that fetal
      growth and development is strongly linked with maternal supply of essential
      nutrients, e.g. vitamins. The exact role of the variety of micronutrients in
      fetal growth and development has yet to be explored in detail. It is estimated
      that up to 30% of pregnant women suffer from a vitamin deficiency. Without
      supplementation, about 75% would show a deficit of at least one vitamin.
      Moreover, multivitamin deficit combinations often co-exist, and subclinical
      depletations are probably common; consequences could be severe. Studies carried
      on in developing countries have shown that improving micronutrient intake in
      deficient women can reduce maternal morbidity and mortality. Also, proper
      maternal intake of important micronutrients directly enhances the quality of
      breast milk. To meet the increasing demands during pregnancy and the
      breastfeeding period women should not be dependent only upon the dietary intake:
      adequate reserve is essential for the successful pregnancy outcome.

PMID- 17039855
TI  - Micronutrients in women's reproductive health: II. Minerals and trace elements.
AB  - It is widely accepted that micronutrients have a major function in many periods
      of women's life, particularly during pregnancy and lactation. Inadequate stores
      or intake of micronutrients might have adverse effects both to the mother
      (hypertension, anemia, complications of labor) and the fetus (congenital
      malformations, pre-term delivery, intrauterine growth retardation). The effect of
      improper nutrition is influenced by gestational age, severity of deficiency, or
      both. Generally, the daily requirements in minerals and trace elements are easily
      met in women having a balanced diet. Such diet during pregnancy should provide
      the recommended daily allowance of all nutrients except elemental iron.
      Consequently, deficiency states are supposed to be rare in developed countries,
      and supplementation should be made on an individual basis. On the other hand,
      nutritional deficiencies during pregnancy might be difficult to detect. Studies
      from developing countries where micronutrient malnutrition is common during
      pregnancy gave us strong evidence that supplementation of certain trace elements
      and minerals could prevent some of the most severe adverse pregnancy outcomes.
      While some micronutrients have been studied extensively (e.g. calcium, iron,
      zinc, iodine), much less is known about others. It has been shown that multiple
      micronutrient deficiencies, rather than single deficiencies, are common. Our
      knowledge about the significance of interactions between micronutrients in
      relation to pregnancy outcome is limited. The role of these interactions in
      improving pregnancy outcome need to be investigated more precisely. According to
      the summarized data, the potential benefits of routine supplementation seem to
      outweigh any potential adverse reaction that can be attributed to their
      consumption.

PMID- 17039856
TI  - Menopacenutrient therapy: an alternative approach to pharmaceutical treatments
      for menopause.
AB  - Considerable controversy surrounds the use of hormone replacement therapy (HRT)
      for treatment of peri-menopausal symptoms. Recent publications from three large,
      prospective randomized studies call the safety of HRT into question, and leave
      patients searching for answers. Nutrient therapy may provide symptomatic relief
      without increasing risk of chronic disease. In this study, results of a series of
      uncontrolled prospective studies of peri-menopausal symptom relief using Menopace
      nutrient therapy were combined to provide a broad perspective on the safety and
      effectiveness of this alternative treatment modality. Data from seven studies
      with a total of 766 subjects were analyzed. Subjects with specific menopausal
      symptoms reported improvement after three months of daily use of the therapy,
      ranging from 87.8% of subjects with hot flashes to 67.5% of subjects with poor
      concentration reporting improvement. Overall improvement in menopausal symptoms
      was reported in 93.2% of all subjects. These results provide consistent evidence
      of the effectiveness of comprehensive, nutritionally balanced nutrient therapy
      for treatment of menopausal symptoms. While most evidence-based practitioners
      focus primarily on research results from randomized, controlled clinical trials,
      other forms of research evidence can also guide clinicians searching for safe and
      effective treatment options for their patients.

PMID- 17039857
TI  - Does the use of folic acid increase the risk of twinning?
AB  - The increased rates of twinning and the increased consumption of folic acid are
      two parallel processes described in recent years. However, the possible
      association between an increased incidence of twin pregnancies and
      periconceptional folic acid supplementation remains controversial. Whereas the
      data indicating that when folic acid levels are increased to the range required
      for reducing the incidence of neural tube defects, the data pertaining to the
      increase in twinning rate are significantly incoherent and are flawed by serious
      confounders, such as fertility treatments and maternal age. The only plausible
      theory connecting methyltetrahydrofolate reductase mutation, folic acid, and
      twinning has not been confirmed. In addition, temporal and dose-effect
      relationships have not been established. Because of the lack of coherence,
      questionable plausibility, and no clear dose-effect and temporal relationships, a
      cause (folic acid supplementation) and effect (increased twinning rate)
      association cannot be, at present, accepted. Thus, the established policy of peri
      conceptional folic acid supplementation to reduce the incidence of neural tube
      defects should be continued.

PMID- 17039858
TI  - Rate of blastocyst development from excess embryos remaining in culture after day
      3 embryo transfer.
AB  - OBJECTIVE: To assess the rate of blastocyst development (BDR) from embryos
      remaining in culture after day-3 embryo transfer (ET), and its relationship to
      cause of infertility. STUDY DESIGN: Retrospective cohort study in tertiary-care
      IVF Center. Blastocyst development rate (BDR) after day-3 ET was assessed in 126
      women who underwent either conventional IVF or ICSI. RESULTS: Mean age, early
      follicular FSH levels, number of 2PN zygotes, number of excess embryos, and
      number of ET were similar between patients that underwent IVF and ICSI. Overall,
      20% of extra embryos from conventional IVF patients developed into blastocysts
      compared to 14% of embryos obtained from ICSI. Cause of infertility did not
      affect BDR, even in patients who required ICSI due to male factors. CONCLUSIONS:
      Low rates of blastocyst development from excess embryos are similar between IVF
      and ICSI patients. Only 15 to 25% of excess embryos left in culture develop into
      blastocysts, regardless of cause of infertility. Physicians and patients can use
      this information to adjust both AR treatment protocols and patient expectations.

PMID- 17039859
TI  - SUMEVA, a new system of climacteric symptom evaluation, and its correlation with
      FSH and estradiol levels.
AB  - OBJECTIVE: To evaluate a new climacteric symptom scale (SUMEVA) and to assess its
      correlation with follicle stimulating hormone (FSH) and estradiol (E2) levels.
      METHODS: 115 healthy perimenopausal women who were not receiving, nor had
      received, hormone therapy were studied. They were asked to complete 3
      questionnaires concerning climacteric symptoms: (1) Kupperman's index (KI), (2)
      Green scale (GS), and (3) SUMEVA, which is the sum of symptom evaluations done in
      an analog visual scale. FSH and E2 determinations were done by chemoluminiscence.
      STATISTICAL ANALYSIS: The comparison among the groups was done by Student's t
      test. Pearson correlation analysis was done between FSH and E2 levels and KI, the
      GS, and SUMEVA. RESULTS: There were 60 women with FSH < or = 30 mIU/mL (group I)
      and 55 with FSH > 30 mIU/mL (group II). The KI average in the whole group was
      13.2 +/- 8.1, the GS 20.6 +/- 13.1, and the SUMEVA 65.6 +/- 44.9. The three
      scales had a significant correlation between them. CONCLUSIONS: No correlation of
      KI, GS, or SUMEVA was found with FSH and E2 levels, but the SUMEVA was as
      effective as the other previously validated, scales for climacteric symptom
      evaluation.

PMID- 17039860
TI  - Characterization of dental fillings found in skulls from individuals buried in
      San Jeronimos Church, New Spain: historical and archaeological evidences.
AB  - Repair of teeth during the XIX century was often a very costly and painful
      procedure. During this period, restoration of teeth was a procedure limited only
      to those who could afford such care. In this study we analyzed teeth from a skull
      sample found in San Jeronimo's Church. The characterization of molar fillings was
      made with techniques such as X-ray fluorescence, X-ray diffraction and electron
      microscopy. The purpose of this investigation was to establish technical
      procedures for analysis, and to discuss the results within the context of the
      socioeconomic status of these individuals and the written descriptions of the
      dental practice during the XIX century.

PMID- 17039861
TI  - Leroy E. Burney, MD, MPH: quiet champion of American dentistry and dental
      research at mid-century.
AB  - Leroy E. Burney was a preeminent Surgeon General and was recognized for
      modernizing the Public Health Service. He promoted environmental public health
      and access to health care for the poor. He oversaw major expansion of health
      professions' education and research, and he was the first public official to
      alert America to the link between cigarette smoking and lung cancer. Historical
      accounts of Burney's legacy have not focused on his remarkable contributions to
      dental public health. The aim of this study was to elucidate Burney's role over
      four decades in promoting the interests of dentistry in America, through his
      support of dental science, dental education, and public access to dental health
      services. Burney engaged in dental research and developed a model dental public
      health program for Indiana. As Surgeon General, he oversaw dramatic expansion of
      dental research and education and the building of the National Institute for
      Dental Research. A skillful collaborator, Burney worked toward common goals with
      leaders of American dentistry and Congress. He was one of the few physician
      members of the Trustees of the American Fund for Dental Education. A humble man,
      Burney was a quiet champion of American dentistry and dental research for almost
      forty years.

PMID- 17039862
TI  - Benjamin Franklin and the dentist: the story of R. C. Skinner.
AB  - Among Benjamin Franklin's papers was a letter from a young British immigrant, R.
      C. Skinner, asking for a loan of only twenty dollars to help this young man begin
      the practice of dentistry in this country. Although we don't know what the great
      man's response was to this appeal, Skinner went on to achieve fame in his
      profession. He was the first dentist ever, in this country, to be appointed to a
      hospital staff; he established the first free dental clinic for the poor; and he
      authored the first book on dentistry ever published in America, earning him the
      title "The Father of American Dental Literature." From a newspaper advertisement
      of 1794, further information has been gleaned about Skinner's practice: he not
      only did conventional dentistry, but also supplied missing eyes, ears, noses and
      legs. This was a forerunner of the contemporary subspecialty of prosthodontics
      termed "maxillofacial prosthetics". An interesting list of Skinner's services and
      his fees for each, gives us a good picture of what dentistry was like in Colonial
      America.

PMID- 17039863
TI  - The students of Edward Hartley Angle, the first specialist in orthodontics: a
      definitive compilation.
AB  - Edward Hartley Angle, MD, DDS, (1855-1930) was ardent in making orthodontics a
      distinct specialty. In 1900, he founded the first school in the world devoted to
      specialty training in orthodontics, the Angle School of Orthodontia in St. Louis,
      Missouri. Over the next 30 years, the Angle School moved from St. Louis to New
      York City to New London, Connecticut, and finally to Pasadena, California. There
      was always some uncertainty regarding the accuracy of lists of graduates of the
      Angle School, since the associated prestige was often a lure for false
      representation by some practitioners. The purpose of this article is to delineate
      an authoritative list of Angle's students. Recent additions to primary source
      material help in reconstructing Edward Angle's seminal educational contributions.
      From 1900 to 1930, Angle taught orthodontics to 198 students of which 185
      received certificates of course completion. The remaining 13 received some
      training from Angle, but did not complete his formal course for a variety of
      reasons. He was highly selective in choosing the best dentist-students. Among his
      students were 8 women, 6 Canadians and 27 from 15 countries outside North
      America. Angle's graduates invariably became worldwide leaders and contributors
      in orthodontics in the first half of the 20th century.

PMID- 17039864
TI  - Gleanings about dentistry from the world of literature (thirty-seventh in a
      series).

PMID- 17039865
TI  - Dentistry on stamps. Chewing gum.

PMID- 17039866
TI  - The Thomas W. Evans Museum and Institute revisited. 1907.

PMID- 17039867
TI  - Renee Reijo Pera. Infertility researcher, UCSF.

PMID- 17039868
TI  - Getting back on track.

PMID- 17039869
TI  - Science and the gender gap.

PMID- 17039871
TI  - [Study on melanin from taihe silky fowl and its complexes with Cu2+, Fe3+ ions by
      IR spectrum].
AB  - OBJECTIVE: The interaction between Cu2+, Fe3+ and Melanin from Taihe Silky fowl
      for different pH values was investigated in heterogeneous system. METHODS: The IR
      spectrum of melanin and its complexes with Cu2+, Fe3+ ions was determined.
      RESULTS: The carbonyl group of melanin may interact with metals. CONCLUSION:
      Taihe Silky fowl melanin is the mixture of pheomelanin and isomelanin.

PMID- 17039870
TI  - [Preliminary study on the characteristics of Bupleurum chinense in nutrition
      uptake].
AB  - It was studied that the characteristics of Bupleurum chinense DC. in nutrition
      uptake based on potted and field experiment to provide a properly fertilizer
      application measure. The result showed that the absorption amounts of N, P and K
      were in the order of K > N > P under field condition. For one-year-old B.
      chinesnse DC., the average N, P2O5 and K2O absorption per 100 kg dry matter of
      root were 11.77 kg, 2.43 kg, 14.07 kg respectively; for two-year-old, the average
      N, P2O5 and K2O absorption amount per 100 kg dry matter of root were 12.11 kg,
      2.74 kg, 18.39 kg respectively. The total absorption amount of N, P2O5 and K2O
      were lower in the first year, while the percentage of content was higher, that
      was to say, the demand for N, P and K was urgent in the first year. The
      accumulation peak of N, P2O5 and K2O occurred regreening to later elongation
      stage in the second year. The ratio of N, P and K were differential in different
      growth stages.

PMID- 17039872
TI  - [The analysis on processed chrysanthemum by FTIR spectrums second-order
      derivative spectrums and two-dimensional spectrums].
AB  - Using Infrared spectrums, Second-order derivative spectrums and Two-dimensional
      spectrums to analyze Chrysanthemum and processed Chrysanthemum in henan province,
      the infrared characters of Chrysanthemum and processed Chrysanthemum can be
      found.

PMID- 17039873
TI  - [Study on the TLC-fingerprint of Xiatianwu].
AB  - OBJECTIVE: To develop a method that can well evaluate the quality of Xiatianwu.
      METHODS: Methods are researched and discussed to construct the TLC-FP (thin-layer
      chromatography finger-print) of Xiatianwu to evaluate its quality. RESULTS: The
      areas of six evident peaks in the thin-layer chromatography of Xiatianwu are
      compared with the area of dl-tetrahydropalmatine peak companied with them in the
      same chromatography. The Rr of every peak and its relative area were acquired to
      evaluate the quality of Xiatianwu and identify it. CONCLUSION: The TLC
      fingerprint of Xiatianwu can well evaluate the quality of Xiatianwu.

PMID- 17039874
TI  - [The identification of microscopic, physical and chemistrical analysis on
      Curculigo orchiode and its counterfeit].
AB  - OBJECTIVE: To identify sham Curculigo orchiode from the genuine. METHODS: Using
      the distinguishing method of morphology and histology, TLC and UV spectrum
      analysis. RESULTS: The tissue structrue, the physical and chemical featrures of
      Curculigo orchiode and its counterfeit have obvious differences. CONCLUSION: The
      counterfeit of Curculigo orchiode come from Paeonia lactifora's axillary root.

PMID- 17039875
TI  - [Chemical constituents from the south China sea gorgonian coral Subergorgia
      reticulata].
AB  - Nine compounds, cholesterol (1), ergostra-7,22-diene-3beta, 5alpha, 6beta-triol
      (2), cholesta-7,22-diene-3beta, 5alpha, 6beta-triol (3),5,8-epidioxycampesta-6,22
      dien-3-o1 (4), batyl alcohol (5), theine (6), thymine (7), uracil (8), guanine
      (9), were isolated from the South China Sea gorgonian coral Subergorgia
      reticulata and their structures elucidated on the basis of spectral data. All of
      these compounds were isolated for the first time from this gorgonian coral.

PMID- 17039876
TI  - [Study on the chemical constituents of Mitragyna rotundifolia].
AB  - Twelve compounds were isolated from the EtOAc-soluble and ButOH-soluble portions
      of the EtOH extract from the bark of Mitragyna rotundifolia. These compounds were
      identified by their spectral data as dauricine (1), 3,4-dihydroxybezoic acid (2),
      beta-sitosterol (3), scopleton (4),3,4,5-trimethyoxyphenol-1-glucopyranoside (5),
      taraxerol (6), 4-hydroxy-3-methyloxybenzoic acid (7), 3-hydroxy-4
      methyloxybenzoic acid (8), caffeic acid (9), gambirine (10), gambireine (11),1,1
      dimetheyl-2-acetl-diethyl ether (12), respectively. All compounds were isolated
      from this genus for the first time.

PMID- 17039877
TI  - [Studies on phloroglucinol derivatives of Dryopteris fragrans L].
AB  - OBJECTIVE: To study the phloroglucinol derivatives of Dryopteris fragrans.
      METHODS: Isolation and purification were carried out on repeated silica gel,
      Sephadex LH-20 column chromatography and prepare HPLC. The structures of the
      compounds were determined by physicochemical properties and spectral analysis.
      RESULTS: Four compounds were isolated and identified as aspidin PB (I),
      dryofragin (II), aspidinol (III), aspidin BB (IV). CONCLUSION: Compounds IV is
      isolated from this plant for the first time.

PMID- 17039878
TI  - [Studies on the chemical constituents of essential oil of Hunan Artemisia annua].
AB  - The chemical constituents of the essential oil of Hunan wild Artemisia annua L.
      in Xuefeng mountain region have been studied by means of the GC-MS. The essential
      oil was extracted from Artemisia annua L. by steam distillation. The chemical
      constituents were separated and identified by GC-MS, and the relative contents of
      them in the oil were determined with area normalization method. Forty-five
      components were separated and identified which accounted for 90% of total
      essential oil. These components identified from the essential oil indicate that
      Hunan wild Artemisia annua L. in Xuefeng mountain region is a good medical plant,
      and worth to exploiting.

PMID- 17039879
TI  - [Deterimination of schisandrin in Kadsura heteroclita (Roxb.) Craib by RP-HPLC].
AB  - OBJECTIVE: To develop a method of RP-HPLC for determination of schisandrin
      content in Kadsura heteroclita (Roxb.) Craib. METHOD: RP-HPLC analysis was
      carried out by using Kromasil C18 column (5 microm, 250 mm x 4.6 mm) and methanol
      water (65:35) as the mobile, and the detection wavelength was 250 nm. RESULTS:
      The method was linear in the range of 0.08-0.06 nicrog (r = 0.9998), and the
      average recovery was 100.24%, with the RSD of 2.09% (n=5). CONCLUSION: The method
      was simple, accurate, highly sensitive and reproducible. It may be used for the
      quantitative determination of schisandrin in extract of Kadsura heteroclita
      (Roxb.) Craib.

PMID- 17039880
TI  - [Harmine induces apoptosis in human SGC-7901 cells].
AB  - OBJECTIVE: [corrected] To investigate the effect of apoptosis induced in human
      SGC-7901 cells by Harmine. METHODS: The effect of Harmine on human SGC-7901 cell
      survival and apoptosis was determined by MTT assay, light microscopy and flow
      cytometry. Cell genomic DNA was detected by agarose electrophoresis. RESULTS: The
      survival of human SGC-7901 cells decreased; Apoptotic cells were observed by
      fluorescent microscope; FCM analysis showed that the peak of apoptosis increased.
      Typical DNA Ladder were detected in DNA agarose gel electrophoresis. CONCLUSION:
      HM can induce apoptosis in human SGC-7901 cells.

PMID- 17039881
TI  - [The study on angiogenesis activity of danggui, chuanxiong and danshen].
AB  - OBJECTIVE: To observe the effect of danggui (Radix angelicae sinensis),
      chuanxiong (Rhizoma chuanxiong) and danshen (Radix salvae miltionrrhizae) on
      cardiac microvascular endothelial cells (CMECs) obtained from rat and
      quantitation of vessels on chick embryo chorioallantoic membrane (CAM) model.
      METHODS: Normal rat cardiac microvascular endothelial cells (CMECs) were cultured
      by collagenase and trypsin and the influences of the herbs on the CMECs were
      observed by cell count and MTT colorimetry. The activity of blood vessels was
      determined by quantitation of vessels on chick embryo chorioallantoic membrane
      (CAM) model. RESULTS: Compared with the normal group, after treatment with
      chuanxiong of high dosage, danggui of high and middle dosages, danshen of high
      and middle and low dosages, they enhanced proliferation significantly (P < 0.05).
      The two later could be in dependent dose. And the herbs might increase
      quantitation of vessels on CAM. CONCLUSION: These Chinese herbs may promote
      angiogenesis by stimulating proliferation of CMEC and incresasing blood vessels.

PMID- 17039882
TI  - [Effect of the ethyl acetate extract of zhi ju zi on serum makers and the
      expression of TGF-beta1 in rats with hepatic fibrosis].
AB  - OBJECTIVE: To study the effect of the Ethyl Acetate Extract of Zhi Ju Zi on
      hepatic fibrosis. METHODS: Model of liver fibrosis in rats was induced by CCl4.
      The level of hyaluronic acid (HA) and laminin (LN) was detected by RIN. The
      expression of TGF-beta1 of the rat liver was detected by RT-PCR. RESULTS: After
      treatment, the level of HA was apparently decreased (P < 0.05); the level of LN
      wsn't apparently different with the Colchicin group (P > 0.05); The expression of
      TGF-beta1, was apparently decreased (P < 0.05) CONCLUSION: The Ethyl Acetate
      Extract of Zhi Ju Zi can effectviely decrease the level of serum markers of
      hepatic fibrosis and the expression of TGF-beta1.

PMID- 17039883
TI  - [Studies on extraction process optimization of Panax notogingseng saponins].
AB  - OBJECTIVE: To optimize the conditions for the extraction of panax notogingseng
      saponins (PNS). METHODS: After selected extraction solvent and suitable particle,
      we employed orthogonal experimental design to examine the conditions for the
      extraction by determination of PNS. RESULTS: Significant effect was observed only
      in extraction times. CONCLUSION: The optimum condition for extraction of PNS was
      to extract panax notogingseng (Burk.) F. H. Chen with 10 times 70% ethanol for
      1.5 hours for 3 times.

PMID- 17039884
TI  - [The extraction, purification and assaying of Gynostemma pentaphyllum
      polysaccharides].
AB  - By orthogonal design, and considering extracting efficiency and cost, optimizing
      the extract method of Gynostemma pentaphyllum polysaccharides. We purified the
      crude Gynostemma pentaphyllum polysaccharides initially, and assayed the
      polysaccharides content of Gynostemma pentaphyllum polysccharides. The content of
      Gynostemma pentaphyllum polysaccharides was sigificantly higher than the
      predecessor. It would provide conditions for the deep exploitation of Gynostemma
      pentaphyllum.

PMID- 17039885
TI  - [Research on extracting process for compound shenzhutiaozhi capsule].
AB  - OBJECTIVE: The technics of optimal extraction for compound shenzhutiaozhi capsule
      is investigated in this study. METHODS: Orthogonal test were employed for
      selecting the optimum of extraction technics and the contents of oleanolic acid
      and salvianolic acid B were detected by TLC-scanning and HPLC, respectively.
      RESULTS: Five volume of 70% alcohol, extracting 3 times with half an hour for
      each time, and seven volume of water, extracting 3 times with half an hour for
      each time were considered the optimum extraction technics of Frugtus Ligustri
      lucid, Salvie miltiorrhizae as well as Reizaoma Atractylodis Macrocfphalae,
      respectively. CONCLUSION: The considerable extraction rate of active components
      in the drugs is achieved by applying the selected technics.

PMID- 17039886
TI  - Research progress on anti-diabetic Chinese medicines.
AB  - Diabetes mellitus (DM) is commonly known as Xiaokezheng ([Chinese characters: see
      text]) with respect to the sign of imbalance of yin, yang and qi in the
      traditional Chinese medical system. This review is mainly focused on peer
      reviewed international journals in chemistry, pharmacological and clinical
      research of Chinese medicines (CM) used in therapeutic treatments of DM and its
      complications. This article will also discuss the advantages and future
      perspectives of anti-diabetic CM.

PMID- 17039887
TI  - [The effect of shanzha xiaozhi capsule on the blood lipid and the function of
      endothelial cells in patients with dislipide mia].
AB  - OBJECTIVE: To explore the Mechanism of Shanzha xiaozhi Capsule improving the
      functions of endonthelial cells in patients with dislipide mia. METHODS: To
      measurate the blood lipid and the levels of plasma Endothelin (ET) and nitrodi
      oxide (NO) in 30 patients with dislipide mia before and after taking the Shanzha
      xiaozhi Capsule, and there were 10 normal persons in control group, which were
      measured the blood lipid and the levels of ET and NO only one time. RESULTS:
      After treatment with Shanzha xiaozhi Capsule, the levels of triglyceride (TG),
      total cholesterol (TC), low density lipoprotein cholestero (LDL-C), ET were
      markedly reduced (P < 0.05), and the levels of NO were obviously elevated (P <
      0.05). CONCLUSION: Shanzha xiaozhi Capsule can reduce blood lipid level and the
      plasma ET levels, increase the NO levels and the protection to the functions of
      endothelial cells which might be involved in the mechanisms of against
      atherosclerosis.

PMID- 17039888
TI  - [Tuberculosis--a permanent problem].

PMID- 17039889
TI  - [Significance of ultrasonography of the terminal ileum in moderate Crohn's
      disease].
AB  - BACKGROUND/AIM: Crohn's disease (CD) is a chronic granulomatous inflammatory
      disease of unknown etiology, involving any part of the gastrointestinal tract,
      and frequently followed by extraintestinal manifestations. The use of
      ultrasonography plays a significant role in diagnosing this disease, as well as
      in monitoring the effects of the therapy. The aim of this study was to assess the
      use of ultrasonographic diagnostics in the patients with moderate serious and the
      mild form of CD. METHODS: The study involved 30 patients both sexes with CD of
      moderate form determined using the standard diagnostics, according to the Crohn's
      Disease Activity Index--CDAI ranging from 220-400. The patients were divided into
      two groups with CDAI > 320 (Ia), and CDAI between 220 and 320 (Ib), respectively.
      The Control group was made of 19 patients with the mildly active stage of the
      disease and the CDAI values in the range from 100-220. The patients were
      submitted to an ultrasonographic examination of the terminal ileum affected with
      CD in order to determine the length of the affected segment of intestine, the
      thickness of the wall, the changes of the structure of the wall, the changes of
      the surrounding mesenterium with the enlarged lymph nodes. CD complications,
      abscesses, and enteroenteral fistulas were investigated, too. RESULTS: The
      comparison of the ultrasonographic findings of the three groups revealed that
      more serious clinical-laboratory image of CD significantly correlated with the
      higher length of the affected segment (p < 0.001), higher thickness of the wall
      (p < 0.001), the higher number and the larger lymph nodes of the mesenterium (p <
      0.001). Only the most serious patients were found to have abscess of the
      ileocecal area (Ia - 40%). There was no difference found between the groups
      regarding the occurrence of enteroenteral fistulas. CONCLUSION: Considering the
      obtained results and data from the literature, it could be concluded that an
      ultrasonographic examination of the ileocecal area plays an important role in the
      diagnostic procedure in the management of a patient with CD. Of particular
      significance is the possibility to use this examination in monitoring the effects
      of the therapy in patients with CD.

PMID- 17039890
TI  - [Roentgencraniometric evaluation of the craniofacial dimensions in subjects with
      symptoms of temporomandibular disorders].
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the possible association
      between certain morphologic features of the craniofacial skeleton and the
      presence of symptoms of temporomandibular disorders in young subjects with
      natural dentitions. METHODS: The investigation was carried out on 80 lateral
      cephalometric radiographs of two groups of male and female subjects between 18
      and 25 years of age with natural dentitions. The analysed group consisted of 30
      subjects with symptoms of temporomandibular disorders, and the control group of
      50 subjects without such symptoms. According to the values of the ANB angle
      (position of the maxilla with the mandible-Steiner cephalometric analysis) all
      subjects were classified in the skeletal class 1. The roentgencraniometric
      analysis of cephalometric radiographs included the evaluation of 25 linear
      dimensions which values were compared between the examined groups and with the
      values of the same dimensions in the Bolton standards for 18 years of age.
      RESULTS: The results of this study confirmed the presence of significant
      differences between the examined linear dimensions in the Bolton standards and
      the same dimensions measured in the subjects of the analysed and the control
      group. The comparative analysis of these values between the groups confirmed the
      presence of significant differences in following linear dimensions at the level
      of p < 0.00: S - Cs(Go), Mol - PP, Mol - MP and Ar - Go. CONCLUSION: Significant
      differences between the examined linear dimensions measured in the subjects
      included in this study and the same dimensions in the Bolton standards can be
      explained by specific morphologic features of the craniofacial skeleton in people
      of our population. Within the limitation of this study, the minor differences in
      the values of the examined linear variables between the subjects of the
      experimental and the control group can not be accepted as indicators of disturbed
      function of the orofacial system.

PMID- 17039891
TI  - [Use of the modified Fries technique in the reconstruction of the lower lip after
      the removal of a malignant tumor].
AB  - BACKGROUND/AIM: Lip carcinoma makes about 1/4 of all oral carcinomas. Primary
      treatment of the lower lip carcinoma means radical excision of the full thickness
      of the lower lip tissue together with the tumor. The reconstruction of the defect
      accomplished after the removal of the lower lip tumor is a challenge for the
      surgeon and requires a detailed preoperative planning, the right choice of the
      method for reconstruction and the knowledge of the adequate surgical techniques
      needed. The aim of this study was to presenta ten-year clinical results and
      experience concerning the reconstruction of lower lip defects longer than 4 cm by
      means of the modified Fries method in patients treated for the lower lip
      carcinoma. METHODS: The reconstruction of the lower lip by means of the modified
      Fries method was performed in 37 patients. The following parameters were
      analyzed: sex, age, the time elapsed from the occurrence of the first symptoms
      until the first consultation with the doctor, the size of tumors, the size of the
      postexcision defect, TNM classification, the application of side diagnostic
      procedures, pathohistological diagnosis of postoperative complications. The
      sensibility of the lower lip region was monitored, as well as the obtained
      esthetic effects. RESULTS: The results classified according to the mentioned
      parameters were processed, analyzed and displayed in detail. Clinical experience
      concerning the application of this reconstruction technique was presented and
      analyzed. CONCLUSION: The modified Fries technique can successfully be applied in
      the reconstruction of the lower lip defects longer than 4 cm because its
      application leads to satisfactory functional and acceptable esthetic results.

PMID- 17039892
TI  - [Methods of the physical medicine therapy in prevention of heterotopic
      ossification after total hip arthroplasty].
AB  - BACKGROUND/AIM: In the prevention of periarticular heterotopic ossification (HO),
      a common complication after total hip arthroplasty (THA), nonsteroidal
      antiinflammatory drugs (NSAID) and irradiation are used. Some theories presume
      that local hypoxia of the soft tissue causes HO. The aim of this study was to
      investigate if the early use of pulsed electromagnetic fields (PEMF) could
      prevent this ossification since it accelerates the circulation and oxigenation of
      soft tissue. METHODS: The study included three groups of the patients with
      primary THA. The group C consisted of 66 patients/79 hips who had only
      kinesitherapy in postoperative rehabilitation. The group B consisted of 117
      patients/131 hips who had PEMF and interferential current (IC) which, on average,
      started on the 14th day after the surgery combined with the standard
      kinesitherapy. The group A consisted of 117 patients/131 hips who had PEMF from
      the third postoperative day and IC from, on average, the 14th postoperative day
      with the standard kinesitherapy. The classification of HO was done on a standard
      AP roentgenograms of the hips, taken at least one year after the surgery.
      RESULTS: The overall HO was seen in 50.63% of the group C patients, in 43.51% of
      the B group and in 16.67% of the group A. Severe HO (III and IV class according
      to Brooker) was seen in 26.58% of the group C patients and in 6.10% of the group
      B, but none in the group A. CONCLUSION: According to the obtained results an
      early treatment with PEMF could prevent severe HO and reduce the overall HO.

PMID- 17039893
TI  - [Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1
      in ovarial carcinomas].
AB  - BACKGROUND/AIM: Among the genes involved in ovarian carcinogenesis, there has
      been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the
      genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome
      guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations
      are found mostly in breast and ovarian cancer. The aim of this investigation was
      to establish the frequency of loss of heterozygosity (LOH) in the regions of the
      genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH
      with the disease stage and prognosis. METHODS: We analyzed 20 patients with a
      confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic
      analysis was extracted from the tumor tissue and blood as normal tissue of each
      person. Microsatellite markers of the regions of genes p53 and BRCA1 were
      amplified by PCR method. The determination of allelic status of microsatellites
      and detection of LOH was performed after PAA gel electroforesis. RESULTS: Both of
      the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the
      region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had
      histological gradus G1, one had gradus G2, and two of them had gradus G3, while
      all were with the International Federation of Gynecology and Obstetrics (FIGO)
      IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors.
      Four of them had histological gradus G2, and one had gradus G3, while by the
      (FIGO) classification one was with stage Ib, one was with stage IIIb, while the
      three were with stage IlIc. LOH in both of the analyzed regions was detected in
      one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage.
      CONCLUSION: The frequency of LOH in epthelial ovarian carcinomas was 30.7% and
      38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had
      histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the
      association of this occurrence with a later phase of the disease.

PMID- 17039895
TI  - [Pulmonary barotrauma].

PMID- 17039894
TI  - Histopathology of chronic hepatitis C in relation to virus genotype.
AB  - BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is
      variable and the factors determining the course of the illness are unclear. There
      are geographical variations in the distribution of different HCV genotypes, and
      some of them are related to the specific infection routes. Regarding our country,
      the dominant genotype is genotype 1b. It is unclear and still remains a question
      whether the distinct histopathological manifestations are related to the
      particular genotypes of HCV. Thus, the aim of this study was to determine whether
      the distinct histopathological manifestations of HCV infection might be in
      relation to the individual virus genotype. METHODS: In this study we examined 126
      patients with chronic HCV infection regarding the histopathological features,
      demographic data, and virus genotype. The observed groups of patients were
      predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we
      found that the patients infected with HCV genotype 1b had more frequently
      moderate or severe necroinflammatory activity of the disease, significantly
      higher grading score as compared with other genotypes (p < 0.0001). A higher
      degree of fibrosis was, also, more common in the patients infected with genotype
      1b of HCV as compared with other genotypes (p < 0.05). There were no significant
      correlations between the necroinflammatory activity of the disease and the stage
      of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support
      the hypothesis that distinct genotypes of HCV are associated with the particular
      histopathological manifestation of the disease.

PMID- 17039896
TI  - [Second-line antitubercular agents and their adverse effects].

PMID- 17039897
TI  - Long-term outcome of strabismus and ptosis surgery in a mother and daughter with
      congenital fibrosis of extraocular muscles.
AB  - BACKGROUND: Congenital fibrosis of extraocular muscles (CFEOM) is a very rare
      congenital condition, characterized by variable amounts of restriction of the
      extraocular muscles, with or without ptosis. The aim of this report was to
      describe a severe, atypical, exposure-induced corneal stromal lysis in two
      patients. CASE REPORT: A mother and a daughter with a severe CFEOM were
      presented. The surgery of both extraocular muscles and ptosis led to a fair
      outcome in mother even 30 years after, and a very good outcome in daughter 4
      years after the treatment. CONCLUSION: Though frequently challenging and
      dissapointing the outcome of surgery of both extraocular muscles and ptosis in
      CFEOM can be favorable even in rather severe cases. To the best of our knowledge,
      the atypical keratolysis we described has not been highlighted in the literature
      on CFEOM so far.

PMID- 17039898
TI  - [Aggressive intraabdominal fibromatosis].
AB  - BACKGROUND: Intraabdominal or mesenteric fibromatosis is a rare benign
      nonmetastatic neoplasm that appears as a sporadic lesion or in patients with
      familiar polyposis. Its evolution is unpredictable. About 10% of the cases shaw a
      very aggressive growth. CASE REPORT: We presented a 22-year-old woman in whom an
      aggressive intraabdominal fibromatosis had appeared during the first pregnancy as
      a well circumscribed ovoid tumor, involving the terminal ileum, the caecum, the
      ascending colon, the right kidney, the ureter, and the right common iliac artery.
      The tumor was excised with right colectomy, nephroureterectomy and resection of
      the involved artery using arterial reconstruction with graft interposition. Two
      years after the surgery the patient developed an inoperable tumor recurrency with
      a fatal outcome. CONCLUSION: In spite of a successful surgical excision during
      the original surgery intraabdominal or mesenteric fibromatosis might have an
      aggressive evolution leading to an inoperable tumor recurrency and a fatal
      outcome.

PMID- 17039899
TI  - [Abdominal compartment syndrome caused by ruptured abdominal aortic aneurysm in
      vena cava].
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is a rapid increase in intra
      abdominal pressure asssociated with multi-organs dysfunction. It is caused mostly
      by abdominal bleeding und massive volume compensation. CASE REPORT: We reported a
      76-year-old patient admitted to the hospital with aortic abdominal aneurysm, 13.7
      cm in diameter, ruptured in vena cava, which caused intraabdominal hypertension,
      the liver and kidney dysfunction, as well as circulation, respiration and
      metabolic disorders. Intraabdominal pressure was measured by bladder manometry.
      Central venous pressure and systemic arterial pressure were monitored
      continuously. Clinical signs were thrill and typical abdominal bruit. Aorto-caval
      fistula was diagnosed by the use of contrast computerized tomography. Caval
      endoaneurysmatic suture and aortobiiliac bypass with 18 x 9 mm Dacron prothesis
      were performed. Haemodynamic changes were mostly corrected during the surgery.
      The complete correction of haemodynamics, liver, kidney, respiration and
      metabolic changes was established in the next few weeks. CONCLUSION: The ACS was
      caused by rupture of abdominal aortic aneurysm in vena cava followed by edema of
      the abdominal organs, retroperitoneum, abdominal wall and ascites. Caval
      endoaneurysmatic suture and aortobiiliac bypass with 18 x 9 mm Dacron prothesis
      solved aortocaval fistula as well as all the organs and metabolic dysfunctions
      caused by ACS.

PMID- 17039900
TI  - Global initiative for the prevention of blindness: Vision 2020--the Right to
      Sight.

PMID- 17039901
TI  - [Clinical trials of statins and fibrates --a meta-analysis].
AB  - INTRODUCTION: Several clinical trials of hypolipidemics showed a decrease in
      mortality by 30-40%, while others showed detrimental or no effects. The question
      remains: which trial should be the basis of clinical decision making in the
      choice of hypolipidemic therapy? MATERIAL AND METHODS: Meta-analysis is a method
      for combining research results of several studies. Effects of statins and
      fibrates with respect to placebo, were assessed by systematic literature review
      and meta-analysis. Medline and CENTRAL databases were searched using the
      following keywords: hyperlipoproteinemia, hypolipidemic agents and individual
      drug names. The main inclusion criteria were as follows: statin or fibrate,
      placebo controlled randomized trial, at least one year treatment on average, at
      least 100 patients per study arm and reported mortality. RESULTS: Fibrates showed
      almost complete absence of treatment effects on mortality with odds ratio of 0.99
      and 95% confidence interval 0.80 - 1.11. The odds for statins were 0.87, 0.80 -
      0.95. DISCUSSION: Despite the absence of treatment effects of fibrates, it is
      noteworthy that inclusion criteria of early fibrate trials focused mainly on
      cholesterol with recent identification of elevated triglycerides as an
      independent risk factor. As fibrates exert the most pronounced effect on
      triglycerides, they still may show effect in target populations. Effects of
      statins are confirmed, but they are noticeably lower than in individual trials
      which are given most publicity. CONCLUSION: Even after several decades of fibrate
      use, conclusive evidence of their beneficial effects still needs to be elucidated
      in appropriately designed trials. However, a beneficial effect of statins on
      mortality decrease has been proven. Meta-analysis has an important role in
      estimating true treatment effects and in the practice of evidence-based medicine.

PMID- 17039902
TI  - [The probability of finding HLA identical or partially matched unrelated donors
      in the population of Vojvodina].
AB  - INTRODUCTION: Allogeneic bone marrow transplantation and hematopoietic stem cell
      transplantation from unrelated donors are treatments of choice for patients
      lacking HLA identical siblings or family matched donors. MATERIAL AND METHODS:
      Class I HLA typing was performed by using a standard microlymphocytotoxicity test
      in 434 unrelated persons from Vojvodina, while, class II HLA typing was performed
      using a modified immunofluorescent technique. The estimated gene frequencies for
      the populations of Crete, Korea, China, Scotland, Romania, and North America,
      were used to calculate phenotype frequencies, the probability of finding HLA
      identical or partially (in 5/6 HLA antigens) matched unrelated donors, the number
      of donors necessary for research, as well as genetic distances between
      populations. RESULTS: The probability of finding HLA identical or partially
      matched unrelated donors for patients from Vojvodina is higher in closely related
      populations with low genetic distances, such as populations of Crete, Romania and
      Scotland. DISCUSSION: The probability of finding HLA identical or partially
      matched unrelated donors is in inverse proportion with the number of unrelated
      donors necessary for research with aim of finding at least one HLA compatible
      donor. CONCLUSION: The probability of finding compatible unrelated donors depends
      on the degree of HLA matching between the donor and recipient, HLA phenotype
      frequencies and the donor pool size. These methodology may have a wider usage,
      because it can be applied in calculating the probability of finding suitable
      genotypically matched donors, by using HLA allele frequencies defined by
      molecular techniques.

PMID- 17039903
TI  - Cigarette smoking and lung cancer trends in Serbia--a ten-year analysis.
AB  - Cigarette smoking is the single most common cause of morbidity and mortality in
      the world, and the most important risk factor for developing lung cancer (LC). LC
      is the most frequent form of cancer in men worldwide. Almost half of the adult
      population in Serbia smokes. The aim of the study was to analyze the incidence
      rate (IR) and trend of LC in Serbia from 1994 to 2003, with special regard to
      tobacco smoking status (TSS). Referral annual reports of the Institute of Lung
      Diseases and Tuberculosis on newly diagnosed cases of LC, categorized by sex and
      TSS, have been analyzed TSS included three categories: smokers, ex-smokers and
      non-smokers. LC IR showed an increasing tendency (RR: 0.2859) with 34/100,000
      population in 2003, and significant differences among districts (6.3
      39.1/100.000). Smokers, ex-smokers, and non-smokers account for 70.3%, 17% and
      12.6%, respectively (p < 0.001). An increasing trend of female lung cancer was
      evident in all three categories, but the most remarkable in smokers. There is a
      clear and urgent need to inform the population on harmful effects of tobacco
      smoking on health and risks for lung cancer.

PMID- 17039904
TI  - [Chronic hepatitis C virus infection: is there a correlation between HCV
      genotypes and the level of viremia?].
AB  - INTRODUCTION: Hepatitis C virus (HCV) RNA status and HCV genotypes have become
      extremely important for exact diagnosis, prognosis, duration of treatment and
      monitoring of antiviral therapy of chronic HCV infection. MATERIAL AND METHODS:
      For the purpose of precise and objective assessment of virologic analyses, such
      as the determination of the number of virus copies and virus genotypes, 110
      patients with chronic HCV infection were tested Genotyping of HCV isolates and
      HCV RNA quantification were performed by using the PCR method. Genotype 1b
      infection was verified in 49.1% of patients, genotype 3a infection was found in
      28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections
      were diagnosed in 9.1% of cases. RESULTS: Patients infected by genotype 1b had
      significantly higher serum HCV RNA level in relation to patients infected by
      other genotypes (p < 0.05). Over 70% of patients infected by genotype 1b had more
      than 2 x 10(6) virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the
      percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately
      7.7 x 10(6) virus copies in 1 ml of blood, which was significantly higher in
      comparison with female patients (2.3 x 10(6) copies/ml; p < 0.05). CONCLUSION:
      Our results are in concordance with the results of other authors reporting that
      genotype 1b is predominant in Europe, as well as significantly higher incidence
      of viremia in patients with genotype 1b infection in relation to other HCV
      genotypes. Based on these results, we can conclude that our patients, most
      commonly, present with severe clinical course of chronic HCV infection and
      require longer treatment (48 weeks), which causes economic problems.

PMID- 17039905
TI  - [Antibiotic prescribing policy of the Republic Health Insurance Fund of
      Montenegro in the period 2000 - 2004: effects of drug utilization reform
      strategy].
AB  - INTRODUCTION: Monitoring of antibiotic prescribing promotes rational use of these
      drugs, reduces costs and slows down the progress of resistance. The objective of
      present study was to analyze the effects of drug utilization reform strategy
      realized by the Republic Health Insurance Fund of Montenegro, during the period
      2000-2004. MATERIAL AND METHODS: This before-after comparative
      pharmacoepidemiological study comprised a sample of 100% prescription only
      antibiotics available in public pharmacies during the period 2000 - 2004. The
      drug use was calculated using ATC/DDD methodology and Wilcoxon's test for matched
      pairs was used in order to calculate the statistical significance of difference.
      RESULTS: Antibiotic prescribing was approximately lower by 12% in 2004 in regard
      to 2000 (12.80 vs. 14.57 DDDs, p > 0.05). The participation of this
      pharmacotherapeutic group in the total drug dispensing has remained almost equal
      (approximately 8%). The highest increase in prescribing was established for
      macrolides (1.05 vs. 1.64 DDDs, 59%); penicillins were also prescribed more
      frequently (6.41 vs. 6.56 DDDs, 2%), but other subgroups were prescribed less
      frequently: cephalosporins--(23%) (3.11 vs. 2.43 DDDs) and quinolones--(63%)
      (1.10 vs. 0.47 DDDs). CONCLUSION: The drug utilization reform strategy showed
      mostly positive effects on antibiotic prescribing during the period 2000 - 2004.
      Further educational activities are necessary in order to establish more rational
      approach to prescribing and utilization of antibiotics.

PMID- 17039906
TI  - [Microsatellite DNA analysis as a tool for forensic paternity testing (DNA
      paternity testing)].
AB  - MICROSATELLITE ANALYSIS: By using serological or HLA-testing, the alleged father
      can be excluded as the biological father, but, regardless of the degree of
      probability, positive paternity results cannot be obtained without DNA testing.
      According to the results of the National Human Genome Project, human genome
      consists of approximately 30.000 genes. The vast majority of human DNA is not
      organized in genes and has no genetic expression or visible function. Non-coding
      DNA contains genetic markers important for human identification. Short tandem
      repeats, or STRs, are a class of microsatellites consisting of tandemly repeated
      sequences of 2 to 6 base pair length monomers. Most of the microsatellites show a
      high degree of polymorphism, which can be evaluated by PCR technique, and used in
      criminalistics, forensic identification and parentage testing. A source of DNA in
      parentage testing are blood samples or buccal swabs which are routinelly used.
      Amplification of isolated DNA can be performed in 25-30 cycles by PCR, and
      fragments are separated by capillary electrophoresis. CONCLUSION: The probability
      of paternity of 99.99% or higher corresponds to the paternity "practically
      proven", indicating that the alleged father is the biological father. Such
      results can be obtained only by DNA testing. DNA-testing laboratories are
      required to conduct validation of laboratory facilities, equipment and staff and
      are subject to permanent control by the society.

PMID- 17039907
TI  - [Attitudes of women and gynecologists towards voluntary sterilization in
      Serbia?].
AB  - INTRODUCTION: Voluntary sterilization is a very effective and safe birth control
      method. Is it, however, accepted as a birth control method in Serbia? This is
      certainly a question that should be explored, regardless of the fact that
      voluntary sterilization is neither accessible nor promoted. MATERIAL AND METHODS:
      The target group included women who decided to terminate their pregnancy, and
      gynecologists from various parts of Serbia. RESULTS AND DISCUSSION: The survey
      results indicate that more than half of women believe that voluntary
      sterilization should be available in Serbia. Also, a large number of surveyed
      women, almost half of them, would undergo voluntary sterilization. Younger women,
      respondents with secondary education, those who gave birth to a desired number of
      children, as well as those who have a good relationship with their partners,
      those who have experienced a great number of induced abortions, namely those who
      wish to use contraception in the future, are more open to voluntary
      sterilization. The majority of gynecologists also think that voluntary
      sterilization should become available in Serbia. Most of them consider
      therapeutic and eugenic reasons as appropriate for surgical sterilization.
      However, gynecologists lack current knowledge about this contraceptive method,
      and would not accept to use voluntary sterilization themselves. CONCLUSION: The
      reasons for individual nonacceptance indicate that many of the registered
      ambivalent or negative opinions can be changed by spreading knowledge on
      voluntary sterilization. Moreover, the knowledge of gynecologists about voluntary
      sterilization should be improved as well.

PMID- 17039908
TI  - [Natriuretic peptides and multimarker approach to risk stratification of patients
      with acute coronary syndromes].
AB  - NATRIURETIC PEPTIDES IN ACUTE CORONARY SYNDROMES: Brain natriuretic peptides
      (BNP) and N-terminal prohormone brain natriuretic peptides (N-proBNP) have been
      shown to provide important prognostic information in patients with acute coronary
      syndrome (ACS). Ischemia may be an important stimulus for BNP release. This does
      not imply, however, that BNP is useful for diagnosing ischemia, and BNP is
      unlikely to prove sensitive or specific enough for this purpose. SIGNIFICANCE OF
      NATRIURETIC PEPTIDES IN ASSESSING PROGNOSIS IN PATIENTS WITH ACUTE CORONARY
      SYNDROMES: In patients with ST-elevation and non-ST-elevation myocardial
      infarction, higher BNP and N-proBNP levels have been shown to predict a greater
      likelihood of death or heart failure, independent of other prognostic factors.
      THERAPEUTIC IMPLICATIONS OF BNP ELEVATION IN ACUTE CORONARY SYNDROMES: Patients
      with BNP or NT-proBNP elevation following ACS are clearly at high risk for death
      and for developement of heart failure, but specific therapeutic implications of
      BNP elevation have not been defined. In particular, it is not known how patients
      with BNP elevation should be treated considering the fact that they have normal
      troponin levels and no clinical evidence of heart failure. MULTIMARKER STRATEGIES
      FOR RISK STRATIFICATION IN ACUTE CORONARY SYNDROMES: It has been shown recently
      that in patients with acute coronary syndromes the risk increased sequentially
      among those with one, two or three elevated biomarkers. THERAPEUTIC APPLICATIONS
      OF CARDIAC BIOMARKERS IN ACUTE CORONARY SYNDROMES: Multimarker strategies, that
      incorporate panels of cardiac biomarkers, are likely to be used in the future for
      risk stratification and for pathophysiologically-guided treatment of patients
      with ACS.

PMID- 17039909
TI  - [Predisposing factors of the migraine syndrome in children].
AB  - INTRODUCTION: The aim of this paper was to define characteristics which could be
      used to recognize groups of children at risk for migraine syndrome. MATERIAL AND
      METHODS: Predisposing factors of migraine syndrome were investigated by
      conducting a poll among 24.828 children aged 3-16, in Vojvodina, during the
      period between 1988-2004. RESULTS: For the purpose of defining recognizable
      characteristics of children with migraine syndrome, a comparison of children with
      migraine headaches, non-migraine headaches, and those without headaches was done
      among 24.828 children. Apart from direct heredity, the following factors should
      be accepted as predisposing factors of migraine syndrome: child's order of birth
      (second child), length of breast-feeding, age at which the ready-made industrial
      food was introduced, as well as the age at which the child started the whole-day
      stay (which is in inverse proportion to the risk of migraine attacks and the age
      of the first symptoms), particularities in behaviour pattern, family social
      status, atmosphere in the family, previous paroxysmal torticollis, episodic
      vertigo of unknown etiology, recurrent abdominal pain, and lack of cerebral
      hemisphere dominance. CONCLUSION: Children with migraine headaches have
      particularities, not clear enough for the time being, but recognition of which is
      necessary for early prevention of migraine syndrome in childhood.

PMID- 17039910
TI  - [The prevalence of craniomandibular disorders in the military population of the
      Republic of Serbia].
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of
      craniomandibular dysfunction (CMD) in the military personnel of the Republic of
      Serbia, as well as the distribution of sings and symptoms of CMD in this
      population group. MATERIAL AND METHODS: The epidemiological investigation
      included 284 male persons between 18 - 25 years of age. The sample consisted of
      Military Academy students, and soldiers from different regions of the Republic of
      Serbia. A questionnaire was designed using Helkimo's clinical dysfunction index
      and sings and symptoms of CMD were evaluated, namely the anamnestic index (Ai)
      and the dysfunction index (Di). RESULTS: According to the anamnestic dysfunction
      index (Ai), 85% of persons among the examined group presented without any
      symptoms of CMD (Ai = 0), 14% had mild symptoms (Ai =1) and 1% had severe
      symptoms of CMD (Ai = 5). Functional analysis of the orofacial system in the
      examined group (evaluation of dysfunction index - Di) revealed, however, that 70%
      of solders had at least one sign of CMD, precisely a dysfunction index Di > 0.
      The analysis of signs and symptoms of CMD revealed that disturbances in
      mandibular kinematics were the most prevalent sign of CMD in this population
      group, which was confirmed in 56% of examined persons. Disturbed functions of
      temporomandibular (TM) joints (click, and reciprocal click, deviation and
      deflection during mandibular opening) were established in 31% of examined
      persons, and sensitivity of TM joints and masticatory muscles during palpation in
      4% of examined persons. Pain during mandibular movements was established only in
      1% of examined persons. CONCLUSION: The results of this investigation point to
      significant prevalence of craniomandibular disorders in the examined population
      group. The incidence of TMJ and masticatory muscle pain in 4% of examined persons
      and of pain during mandibular movements only in 1% of examined persons, points to
      presence of mild or initial types of CMD in this population group.

PMID- 17039911
TI  - [Some psychological characteristics of children and adolescents with vitiligo-
      our results].
AB  - INTRODUCTION: Numerous studies have characterized patients with chronic skin
      disease as psychologically vulnerable, mainly due to the fact that their
      condition affects their social relations and all other aspects of life. The
      purpose of this work was to determine whether there are significant differences
      in the level of anxiety, severity of depressive symptoms, and presence of
      stressful life events between adolescent patients with vitiligo and healthy
      peers. MATERIAL AND METHODS: 33 patients with vitiligo aged 10-15 years, and a
      control group of 60 healthy subjects of the same age, were included in this
      prospective study. A clinical examination was performed to determine the clinical
      types of vitiligo, estimate depressive symptoms using the Birleson Depression
      Scale, and anxiety was evaluated by the Spielberger's scale (State-Trait Anxiety
      Inventory). For determination of the frequency of stressful events, the Risk
      Scale was used. RESULTS: Adolescents with vitiligo did not show more pronounced
      signs of anxiety or depression than healthy subjects; differences were not
      apparent in the Risk Scale either, considering stressful events. DISCUSSION AND
      CONCLUSION: The lack of differences between the two examined groups might be due
      to prepubertal age of the majority of subjects. 63.63% of all children included
      in this study were in the prepubertal age (10-12 years), which is the period when
      they are still not focused on their own body and changes to physical appearance.
      It is possible that early onset of vitiligo is a "protective factor", enabling
      the child to attain compensatory mechanisms to solve the problem of vitiligo
      through various interests and aspirations, which do not depend on physical
      appearance.

PMID- 17039912
TI  - [Ultrasound diagnostics of atherosclerosis in chronic renal insufficiency].
AB  - INTRODUCTION: Atherosclerosis is more frequent in patients with chronic renal
      insufficiency than in general population. The aim of this study was to
      investigate the frequency of atherosclerosis and risk factors in hemodialysis
      patients. MATERIAL AND METHODS: We studied 62 patients (36 male and 26 female;
      mean age, 56 +/- 13 years). The mean time on HD was 65.7 +/- 46.7 months. These
      patient underwent the following examinations: assessments of risk factors, body
      mass index, soft tissue calcification biochemical analyses and Duplex
      ultrasonography of carotid arteries; RESULTS: In two thirds of patients older
      than fifty years, thickening of the intima-media complex was found. No
      statistically significant difference was found in the frequency of
      atherosclerosis regarding sex, tissue calcification, plaque, smoking and Diabetes
      Mellitus. There was no correlation between the thickness of the intima-media
      complex and traditional risk factors for atherosclerosis. However, there was a
      statistically significant correlation among atherosclerosis, age and time on
      dialysis. Atherosclerosis was found in 68% of patients between the age of fifty
      and seventy years. Duration of dialysis and age are statistically significant
      factors for atherosclerosis.

PMID- 17039913
TI  - [Treatment of knee flexion contracture in patients with chronic juvenile
      arthritis--a case report].
AB  - INTRODUCTION: Knee flexion contractures are common after-effects of juvenile
      arthritis. Treatment is usually conservative and may include physical therapy and
      kinesitherapy. Surgical treatment, particularly of the soft parts, indicated for
      contractures resistant to conservative treatment, helps to correct the deformity,
      maintain movements, and relieves pain. Intensive postoperative physiotherapy is
      of special importance. CASE REPORT: A 23-year-old female patient with chronic
      juvenile arthritis since the age of one was admitted for treatment of flexion
      contractures in both knees, muscle hypotrophy, loss of strength and gait
      disability. The patient underwent arthroscopic synovectomy. The operation was
      first performed on the right and after 3 mouths on the left knee. The
      preoperative range of motion in the right knee was 30 degrees - 70 degrees and in
      the left 40 degrees - 80 degrees. The patient underwent intensive physical
      therapy to reduce postoperative swelling of knees and firstly passive and then
      active kinesitherapy. Nine months after the first surgery and six months after
      the second, the range of motion in the right knee was 0 degrees - 100 degrees and
      in the left 0 degrees - 105 degrees. The strength of tested muscles was increased
      and gait was improved. CONCLUSION: Management and rehabilitation of patients with
      chronic juvenile arthritis include maintenance or improvement in position and
      function of joints that is achieved with synovectomy. The results depend on
      combined interdisciplinary rehabilitation, well-experienced staff and pre- and
      post-operative physiotherapy as well as kinesitherapy. Arthroscopic synovectomy
      has many advantages and we believe that it was a better solution than open
      capsulosynovectomy in this patient with chronic juvenile arthritis of the knee.

PMID- 17039914
TI  - [Maternal and fetal death due to placenta previa/accreta in a concealed pregnancy
      -a case report].
AB  - INTRODUCTION: This is a case report of maternal and fetal death due to major
      hemorrhage of a patients with placenta previa/accreta in a concealed pregnancy.
      Bleeding is the leading cause of maternal mortality in obstetrics. Postpartum
      hemorrhage is the most important cause of maternal death. Placenta accreta is a
      severe complication involving an abnormal attachment to the uterine wall so that
      it cannot be easily separated from the uterus. CASE REPORT: Due to the fact that
      one part of the placenta is partially detached, while the other part has grown
      into the uterus, postpartum hemorrhage may occur with lethal outcome, unless the
      mother is hospitalized. Fetal death was caused by severe meconium aspiration. One
      way to prevent such complications is to support legal abortions.

PMID- 17039915
TI  - [Rene Favaloro--a surgeon who has changed the history of coronary disease].
AB  - Rene Favaloro was one of the most distinguished surgeons of the 20th century. He
      was the first to introduce the original technique of aortocoronary bypass
      grafting, entering the new era of coronary artery disease treatment. Working at
      the Cleveland Clinic, together with Mason Sones and Effler, he became a member of
      the medical team which performered the first aortocoronary bypass grafting and
      showed the functional competence of the new graft. Although today percutaneous
      coronary interventions and coronary artery stents have a very important role in
      coronary artery disease treatment, five years after his death aortocoronary
      bypass grafting is the method of choice in selected groups of patients. Nowadays,
      when urgent percutaneous coronary interventions are an important treatment option
      in our country, it is good to remember that this also was the idea of Rene
      Favaloro and Mason Sones, who discussed agressive treatment in the first hours of
      myocardial infarction, and to remember his tremendous contributions and life
      dedicated to cardiosurgery.

PMID- 17039916
TI  - [Basic characteristics of duplex sonography in the assessment of lower limb
      arterial circulation].
AB  - INTRODUCTION: Dulpex and color duplex ultrasonography of lower limb arteries are
      valuable non-invasive diagnostic methods in the pathology of vascular diseases
      and a major step in diagnostics and in follow-up of hemodynamic and morphologic
      characteristics. COLOR DUPLEX SONOGRAPHY: The method consists of image analysis
      and analysis of Doppler information. Real-time-B mode is used to visualize the
      anatomy of blood vessels and other pathological lesions. Doppler information
      based on the Doppler effect determine the pulse wave i.e. the shape of flow
      velocity--hemodynamic characteristics. Spectral analysis is the most important
      element of Doppler examination of the lower limb peripheral arteries. Based on
      the spectral analysis, there are four stages of lower limb arterial disease:
      normal findings--1% - 19% diameter reduction; medium stenosis--artery diameter
      reduction of 20% - 49%; high level stenosis--artery diameter reduction of 50% -
      100%; occlusion--no flow detected within the imaged arterial segment. In the
      first place, both iliac arteries are examined, which is followed with femoral,
      popliteal and crural arteries. The examination of iliac arteries is carried out
      with a 3.5 MHz transducer, and other peripheral arteries of the lower limbs are
      examined with a 7, 5 or 5 MHz transducer. CONCLUSION: Color Doppler is an
      extremely valuable diagnostic method in detecting pathology of the lower limb
      arteries. With high reliability level arterial insufficiency and pathological
      arterial segments are diagnosed by a duplex-Doppler.

PMID- 17039918
TI  - [Clinical appearance and outcome of zone 1 retinopathy of prematurity (ROP)].
AB  - The goal of this clinical trial was to evaluate outcomes of the treatment of
      retinopathy of prematurity (ROP) located in zone 1 (Zone 1 ROP). This disease has
      a specific clinical appearance and poor prognosis. Usually it is difficult to
      identify particular stages of ROP and to indicate treatment while following
      progression of the disease. In the group of zone 1 ROP it is necessary to
      separate transient forms (TF), in which vascularizations reach edges of zone 2,
      from very posterior forms (VPR), in which vascularizations and pathological
      changes are present only in zone 1. There were 24 eyes with zone 1 ROP (15
      children) treated with combination of transcleral laser photocoagulation and
      cryotherapy during the years 2000 till 2005 in our series. Five eyes suffered
      from VPR, 19 eyes from TF. Average follow -up was 24 months. We found better
      outcomes in eyes with TF treated in pre-threshold stage of ROP (10 eyes) than in
      threshold stage of ROP (9 eyes). All 5 eyes with VPR developed unfavourable ROP
      stage IV or V. Zone 1 ROP becomes diagnostic and therapeutic challenge
      considering growing incidence of surviving of newborns with low or very low birth
      weight. Treatment initiation during prethreshold stage of ROP as it is supported
      by ETROP study (Early treatment of ROP) seems to be promising.

PMID- 17039917
TI  - [The human lens' transparence changes in children, adolescents, and young adults
      with diabetes mellitus type I].
AB  - Authors followed up the changes' development of the human lens' transparence in
      213 children and young adult patients with diabetes mellitus type I. As initial
      changes of the lens' transparence they considered the posterior "Y" suture
      accentuation, because it was noticed in 44.4 % of lenses during the first 10
      years of the metabolic disease duration, in contrast to 28.1 % representation of
      this dissociation in the control group of patients without diabetes (p = 0.012),
      and it was always markedly more often in patients with myopia. Substantial
      changes were detected predominantly during the sixth until the tenth year of
      duration of the basic disease as fine subcapsular opacities graded as first
      degree of lens transparency changes in 48 % of eyes. After 10 years of the
      disease duration, the lenses were never clear. Consequently, the changes in the
      transparency in the anterior subcapsular layer associated in 18 %. After 15 years
      of diabetes duration, we detected opacities in the anterior and posterior
      subcapsular layers of the lenses, graded as second degree of lenses transparence
      changes in 85 % of eyes. This subjective evaluating of lenses' opacity changes by
      means of the slit lamp examination was correlated with densitometric examination
      by means of Pentacam camera in a representative sample of 29 patients. In the
      first degree of lenses' transparence changes, the posterior subcapsular layer was
      affected in 50 %, and in the second degree, the opacities in this layer were
      found practically in 90 % of cases. False positive result in clear lenses or
      congenital opacities or "Y" suture was not detected. In general, the affected
      lens transparency did not basically influence the visual acuity and the decrease
      of contrast sensitivity was not statistically significant (p = 0.34). For the
      initial change of the lenses' transparency is also determining the patient's age
      at the onset of the diabetes mellitus type I. The changes are more common if the
      onset of the disease is after the fifteenth year of age as before that (p =
      0.026). The authors also detected sporadic opacities in 4.2 % of eyes, probably
      of congenital origin (out of them, in two patients there was bilateral finding of
      the cerulean cataract) without visual acuity decrease.

PMID- 17039919
TI  - [The use of accommodative lenses for surgical correction of the presbyopia using
      the Prelex method].
AB  - The authors refer about their experience with the surgical correction of the
      presbyopia by means of the Prelex (presbyopic lens exchange) method. Patients,
      who underwent this type of refractive surgery procedure to decrease their
      dependency on glasses correction for far as well as for near vision (12 patients,
      23 eyes) and 1 young female patient (2 eyes) with juvenile cataract and high
      hyperopia, were included in the study. The average age at the time of the surgery
      was 51.0 +/- 5.5 years (range, 19-77 years). The average follow up period of the
      whole group of patients is 9.8 months (range, 1-13 months). Depending on the type
      of the lens implanted, the group was divided into subgroup A with the
      accommodative lens 1 CU produced by Human Optics Company implanted, and subgroup
      B with the accommodative lens Kellan TetraFlex KH 3500 produced by LensTec
      Company implanted. The subgroup A consists of 8 patients (15 eyes) with the
      average preoperative refractive error +2.35 +/- 3.45 diopters. The average
      uncorrected visual acuity of this group was 0.24 +/- 0.18, and the average best
      corrected visual acuity was 0.77 +/- 0.22 at the time before the surgery. The
      average glasses correction for near was +4.1 dioptres, and the uncorrected vision
      for near was Jaeger's table Nr. (J) 13. The B subgroup consists of 5 patients (10
      eyes). The average preoperative refractive error was +2.23 +/- 0.93 diopters. The
      average value of the uncorrected visual acuity before the surgery was 0.43 +/-
      0.28, and the average corrected visual acuity was 0.82 +/- 0.25. The average
      value of the glasses correction for near was +5.25 and uncorrected vision for
      near J 13. The final average postoperative error at the time of the last visit
      was in the A subgroup +0.06 +/- 1.17 dioptres. The average uncorrected visual
      acuity was 0.69 +/- 0.24, and the average best-corrected visual acuity 0.96 +/-
      0.12. The average vision of the patients of this subgroup for near was J 3. In
      the B subgroup we found at the last visit the average final value of the
      postoperative refractive error -0.2 +/- 0.72 dioptres. The average uncorrected
      visual acuity 0.57 +/- 0.22 and the average corrected visual acuity 0.95 +/-
      0.12. Average uncorrected vision for near was J 5. We did not notice any serious
      per- or postoperative complication of this procedure.

PMID- 17039920
TI  - [The quality of vision in premature infants--first results].
AB  - In last years, thanks to the development in neonatology, the numbers of saved
      premature children with high co-morbidity are rapidly growing. Contrary to great
      advances in contemporary neonatology, the saved premature children are not spared
      different health's problems in the future life, including the vision. The main
      cause remains the retinopathy of prematurity and neurological diseases. In the
      study the authors present first results of their examinations of visual functions
      in premature children at the school age comparing with the group of healthy,
      mature children of the same age.

PMID- 17039921
TI  - [The color Doppler ultrasonography in glaucoma diagnosis].
AB  - The insufficiency of the autoregulation at the optic nerve's head may cause the
      glaucoma optic neuropathy (GON). If the long-term stressing exists and an
      additional endurance arises, the autoregulation may fail and significant changes
      of the resistance index (RI) at the central retinal artery (CRA) and at the
      posterior ciliar artery (PCA) can be detected by color flow ultrasonography.
      Resistivity index represents peripheral resistance. It is displayed in numerical
      value 0-1. 0 indicates none peripheral resistance, 1 indicates maximal peripheral
      resistance. The goal of this paper was to determine a risk value of the RI at the
      CRA and PCA that could suggest possible damaging of the optic nerve. Two groups
      of the patients were evaluated in the course of 4 years duration of the study. In
      the I. Group were 72 patients (144 eyes) with GON and with intraocular pressure
      (IOP) 14-24 mm Hg. The II. Group consisted of 25 healthy men (48 eyes) without
      diagnosis of GON and with IOP values 14-20 mm Hg. There were RI measurements at
      all patients at the CRA and CPA at the idle mode and immediately after ordinary
      addition endurance (performing squatting--Master test). The statistical analysis
      by T test was evaluated with value: 0.05. CONCLUSION: According to our findings,
      the difference between RI: 0.12 +/- 0.03 at the CRA at the idle mode and
      immediately after ordinary addition endurance is significant for damaging of the
      autoregulation at the optic nerve's head. For assessment of the insufficiency of
      the autoregulation at the optic nerve's head RI from PCA is not significant.

PMID- 17039922
TI  - [The influence of corneal thickness on level of intraocular pressure in the group
      of healthy persons and patients with primary open angle glaucoma (POAG)].
AB  - AIM: To asses the relation between the level of intraocular pressure (IOP) and
      central corneal thickness (CCT), and to examine the dependence of CCT on age, sex
      and refraction in the control group of healthy persons (CG) and the group of
      patients with POAG. METHODS: The control group was formed by 42 eyes of healthy
      people and 20 eyes of patients with POAG. There were 26 women and 16 men in CG
      with a median age of 27.5 years and a median refraction of 0 D. The study group
      with POAG included 9 women and 11 men, with a median age of 71 years and median
      refraction of 0 D. The corneal thickness was measured with an ultrasonic
      pachymeter and the IOP with an applanation tonometer. RESULTS: A mean IOP level
      in CG was 15,4 +/- 5,6 mm Hg and a mean CCT level 558 +/- 42 microm. In the study
      group of POAG there was a mean IOP level 19,6 +/- 4,6 mm Hg, and a mean CCT level
      562.7 +/- 35.7 microm. In the CG a significant positive correlation was found
      between CCT and IOP (p = 0.01). The dependence of CCT on sex (p = 0.92),
      refraction (p = 0.99) and age (p = 0.41) was not statistically significant. On
      the contrary, in the study group of POAG no significant correlation between CCT
      level and IOP level was found (p = 0.15). The dependence of CCT level on sex (p =
      0.43), refraction (p = -0.08) and age (p = -0.17) was also not statistically
      significant. The difference in the CCT level between CG and the study group of
      POAG was not significant (p = 0.81). The IOP level appeared to be the only
      significant difference between both groups (p = 0.007). CONCLUSION: The level of
      IOP was influenced by CCT only in the control group of healthy persons. This
      dependence was not significant in the group of persons with POAG.

PMID- 17039923
TI  - [Ocular symptoms as an indication for carotid endarterectomy].
AB  - Ocular symptoms can be the first sign of carotid artery stenosis. In our carotid
      endarterectomy patients group were ocular symptoms present in 15%, as the only
      sign (without accompanying neurological signs) in 10.5%. Amaurosis fugax was a
      dominant sign in 56 cases, blindness in 5, quadrantanopia in 3; trochlear and
      oculomotor nerve paresis in one case. Angiography finding of more than 60% ICA
      stenosis according NASCET criteria was an indication for surgery. The operative
      technique per se was a microsurgical endarterectomy with selective peroperative
      shunt application. The 30-d morbidity was 3%--with one case of central retinal
      artery embolization and subsequent blindness and another case of major residual
      neurological deficit due to hyperperfusion syndrome and the resultant capsular
      hemorrhage. Shunt was applied in 3% of cases and microscope was used always since
      the beginning of the dissection up to the final suture. Considering low
      perioperative morbidity/mortality rates the carotid endarterectomy represents an
      important means of brain ischaemia profylaxis. In the process of hemodynamically
      significant ICA stenosis, indication for surgical management the authors
      emphasize the role of ocular signs and symptoms and thus the importance of an
      ophthalmology consultant.

PMID- 17039924
TI  - [How severe eye injuries were treated more than 50 years ago].

PMID- 17039925
TI  - [Research on the progress of neuroprosthesis for the limb motor system].
AB  - This paper reviews the current developing situation of neuroprostheses which are
      based on the functional electrical stimulation (FES) technique and are used to
      provide limb movements. It also discusses the major challenges of
      neuroprostheses, which will be faced in the future development and in the
      clinical applications for the rehabilitation of spinal cord injury and stroke.

PMID- 17039926
TI  - [A study on the interpolation algorithm for the serial-parallel robot-controlled
      HIFU].
AB  - According to the hardware characters of the high intensive focused ultrasound
      (HIFU) serial-parallel robots, this paper presents an algorithm of 2-grade
      interpolation scheme which includes the rough and fine interpolations. Both pre
      acceleration and post-acceleration are employed to meet the restrictive
      requirements of coordinated dynamic performance and the detailed procedure of the
      interpolation algorithm is given too.

PMID- 17039927
TI  - [An image acquisition & processing system of the wireless endoscope based on
      DSP].
AB  - This paper covers an image acquisition & processing system of the capsule-style
      endoscope. Images sent by the endoscope are compressed and encoded with the
      digital signal processor (DSP) saving data in HD into PC for analyzing and
      processing in the image browser workstation.

PMID- 17039928
TI  - [The database and its data sharing of neuropathic images].
AB  - This paper introduces the basic principle and method of establishing a database
      for neuropathic images, and discusses its significance and data sharing. The
      database is composed of three data volumes about basic knowledge for images,
      cranial sectional anatomy and neuropathic images. The data sharing is achieved by
      using a method of linking the dynamic network of neuropathic images with database
      of neuropathic images. There are three searching approaches: catalog searching,
      key words searching and code searching.

PMID- 17039929
TI  - [Construction of a regional information system based on standardization and
      middleware platform].
AB  - In this article, based on the analysis on the regional information system's
      development background and its applications, the construction of the regional
      medical information system through creating the electronic medical record and the
      medicine image data centers is proposed, for information resource sharing. And
      then, the system's software construction and various subsystems functions are
      mainly introduced. Standardization and the middleware platform are suggested as
      the effective way of constructing these two data centers in the present situation
      in our country.

PMID- 17039930
TI  - [Monitoring the depth of anesthesia using a fuzzy neural network based on EEG].
AB  - In this paper, a fuzzy neural network (FNN) is proposed for fusing the anesthesia
      information, and realizing the monitoring of the depth of anesthesia (DOA). EEG
      data from 31 patients undergoing general anesthesia with different anesthetic
      agents, and Kc complexity (Kc), approximate entropy (ApEn) were extracted and the
      fuzzy neural network was trained by 25 samples, and tested by the other 6
      samples. The results show that the outputs of the fuzzy neural network whose
      inputs were Kc and ApEn obtained under the awake state and asleep state, exist
      obvious difference. It can be regarded as an quantitative index to estimate DOA.

PMID- 17039931
TI  - [The application of data mining technology in the hospital management].
AB  - This paper introduces the application and role of data mining technology in the
      hospital management.

PMID- 17039932
TI  - [An introduction of the principle for the middleware based on HL7].
AB  - This article introduces the development of a middleware based on HL7, which
      solves the problem of data integration and sharing effectively and successfully,
      among the hospital internal subsystems and different hospitals' information
      systems.

PMID- 17039933
TI  - [Research and implementation of the registry system of multimedia EMR sharing
      based on XDS-I].
AB  - Referring to XDS-I and RIM of ebXML, we have built a registry system for
      electronic medical records sharing which is introduced, in this paper.

PMID- 17039935
TI  - [Non-linear registration of MR brain images integrated with machine learning].
AB  - This paper presents a machine learning method to select best geometric features
      for deformable brain registration for each brain location. By incorporating those
      learned best attribute vector into the framework of HAMMER registration
      algorithm, The accuracy has increased by about 10% in estimating the simulated
      deformation fields. At the same time, on real MR brain images, we have found a
      great deal of improvement of registration in cortical regions.

PMID- 17039934
TI  - [Segmenting lung fields in serial chest radiographs using both population and
      patient-specific shape statistics].
AB  - This paper presents a new deformable model using both population-based and
      patient-specific shape statistics to segment lung fields from serial chest
      radiographs. First, a modified scale-invariant feature transform (SIFT) local
      descriptor is used to characterize the image features in the vicinity of each
      pixel, so that the deformable model deforms in a way that seeks for the region
      with similar SIFT local descriptors; second, the deformable model is constrained
      by both population-based and patient-specific shape statistics. At first,
      population-based shape statistics plays an leading role when the number of serial
      images is small, and gradually, patient-specific shape statistics plays a more
      and more important role after a sufficient number of segmentation results on the
      same patient have been obtained. The proposed deformable model can adapt to the
      shape variability of different patients, and obtain more robust and accurate
      segmentation results.

PMID- 17039936
TI  - [The study of associated reconstruction using MV linear accelerator and cone-beam
      CT].
AB  - In this paper, we proposed a new scan mode and image reconstruction method, which
      combines the data from both the linear accelerator and the cone-beam CT to
      reconstruct the volume with a limited rotation angle and low sampling rate. The
      classical filtered backprojection method and the iterative method are utilized to
      reconstruct the volume. The reconstruction results of the two methods are
      compared with each other with a relavant anlysis given here.

PMID- 17039937
TI  - [Exploration for building PACS and RIS].
AB  - This article elaborates key points of the PACS and RIS project: its overall
      planning, implementation step by step, integration of PACS and HIS based on IHE,
      and the prudent selection of partners and so on.

PMID- 17039938
TI  - [Development of DICOM software platfrom for medical image communication].
AB  - In this paper, we have brought forward the framework design of DICOM software
      platform, using the SUR-DICOM-Lib software and have completed the connection test
      with the RSNA-CTNT Test Node. PACS, DICOM, realize

PMID- 17039939
TI  - [Research on testing the robustness of DICOM-e-mail secure teleradiology
      systems].
AB  - DICOM-e-mail is a secure teleradiology protocol released by German Radiology
      Society and has already been applied clinically. To improve the robustness of the
      system, the protocol has been upgraded by adding some mechanisms such as system
      feedback. Moreover, a test method is also implemented by sending erroneous mails
      to application software that supports DICOM-e-mail. Through the tests for two
      different DICOM-e-mail teleradiology application, the validity of the new
      protocol is proved and at the same time some bugs are found. The implementation
      of the latest protocol and the general error tests can help to make the whole
      teleradiology system a better robustness. The implementation of DICOM-e-mail
      protocol in our country is also discussed in this paper.

PMID- 17039940
TI  - [A 3-D image reconstruction algorithm based on helical CT raw data].
AB  - A CT 3-D image is reconstructed based on a lot of 2-D slice images. A new 3-D
      image reconstruction method, presented in this paper, is to use the helical scan
      continuity, sufficient condition of image reconstruction and the raw data from a
      few helical scan cycles to reconstruct,by a direct interpolation algorithm, 2-D
      images and then 3-D images.

PMID- 17039941
TI  - [Research on the distributed PACS based on grid technology].
AB  - In this paper, we introduce the grid technology into the design of the
      distributed PACS. First, we analyse the architecture and functions of OGSA-DAI,
      and then, introduce a model of the distributed PACS based on OGSA-DAI, and give a
      detailed analysis on its basic components and workflow. Finally, we make a
      conclusion on the distributed PACS based on grid technology.

PMID- 17039942
TI  - [The application value of the PACS in general hospitals].
AB  - In order to evaluate the diagnostic value of the PACS, the PACS has been applied
      to Dept.of Radiology in Renji Hospital in Shanghai for nearly two and a half
      years. Clinical practice shows that the doctors can work more efficiently and
      accurately by using the diagnostic workstation of PACS. PACS is an inevitable
      development trend of image diagnosis and is playing a more and more important
      role in clinical applications.

PMID- 17039943
TI  - [Study on network architecture of a tele-medical information sharing platform].
AB  - In the article,a plan of network construction which satisfies the demand of
      applications for a telemedical information sharing platform is proposed. We
      choice network access plans in view of user actual situation, through the
      analysis of the service demand and many kinds of network access technologies.
      Hospital servers that locate in LAN link sharing platform with node servers,
      should separate from the broadband network of sharing platform in order to ensure
      the security of the internal hospital network and the administration management.
      We use the VPN technology to realize the safe transmission of information in the
      platform network. Preliminary experiments have proved the plan is practicable.

PMID- 17039944
TI  - [Design and implementation of a medical record management subsystem as a part of
      a telemedical system].
AB  - This paper introduces the work on the design and implementation of a medical
      record management subsystem, which is a part of a telemedicine system based on
      Microsoft .NET. First, an analysis is given on components and structure of
      medical record, together with an explanation for what is needed in a
      teleconsultation, how they should be organized and realized in a database, and
      how to deal with consultation data granularity using XML in combination with
      database; second, the work done during the realization stage is expatiated,
      including system analysis and design, database design, and system implementation.

PMID- 17039945
TI  - [JPIP-based wireless transmission and display of high resolution DICOM medical
      images].
AB  - This paper uses JPIP protocol to transmit and display high-resolution medical
      images through the wireless network. JPIP server extracts medical images from
      PACS system, transforms the format of medical images, and parses and recomposes
      the JPEG2000 codestream. Wireless PDA access and display DICOM medical images
      through accessing the JPIP server.

PMID- 17039946
TI  - [The registration of false teeth and the others].
AB  - The quality control of false teeth should include the control for designing and
      processing. The registration of false teeth should emphasize particularly on the
      qualification of the makers, technology management, quality control and the
      labeling.

PMID- 17039947
TI  - [An investigation of medical devices in use in hospitals in Shanghai Baoshan
      District].
AB  - This article briefly presents the situation of medical devices in use in
      hospitals in Baoshan District, including purchasing, daily management, routine
      maintaining and the usage, and mainly puts forward some existent problems, such
      as less attention to maintenance, irregular operations, nonstandard measurements
      and calibrations, and shortage of relative files. In the end of this article,
      some suggestions are made, for example, to set up a "cooperation team for
      maintenance

PMID- 17039948
TI  - [Automatical updating the application software on the hospital information
      system's client].
AB  - In view of the current predicament of updating the application software on the
      hospital information system's client, the Synchronizer module in PowerBuilder is
      used in combination with some techniques of the windows operation system, in
      order to implement automatic synchronistic updating of the application software
      on the Hospital Information System's client before the program's running.

PMID- 17039949
TI  - Material surfaces and MRSA.
AB  - It appears that our hospitals are facing serious threats from antibiotic
      resistant bacteria, especially meticillin-resistant Staphylococcus aureus (MRSA).
      In this article, some of the new materials related solutions to these threats are
      discussed

PMID- 17039950
TI  - Next generation polymer nanocomposites.
AB  - Developments in nanocomposite technology are giving designers a much broader set
      of combinations of materials and properties to use. This will lead to medical
      devices with mechanical properties and enhanced integration of different
      functions. Some of the possibilities are described here.

PMID- 17039951
TI  - Bonding cyanoacrylates and ultraviolet-curing adhesives.
AB  - This guide to the correct adhesives to use for bonding medical plastics reviews
      recent technological advances and the benefits they offer. Material and design
      considerations are also examined.

PMID- 17039952
TI  - Metal injection moulding for medical devices.
AB  - One moulding process is described here that offers speed and cost savings
      together with precision and robust material properties. New product designers are
      advised to design for it from the outset.

PMID- 17039953
TI  - Strategic planning for U.S. premarket approval submissions.
AB  - The United States premarket approval (PMA) process is costly and time-consuming
      and differs in important ways from the CE-marking process. This article discusses
      the importance of strategic planning for submission of a PMA and the issues that
      should be considered, which can lead to a reduction in the time and cost
      involved.

PMID- 17039954
TI  - Wireless pressure monitoring systems.
AB  - Sensor systems based on micro- and nanotechnologies allow continuous monitoring
      and control of therapeutic procedures. Advances in this area are transferring
      this functionality into long-term, fully implanted systems. Some of these
      developments and applications are described here.

PMID- 17039955
TI  - Thin-client medical devices.
AB  - Designing as little functionality as possible on the device, and placing the
      processing burden on the server, can reduce the cost of medical devices and
      provide other benefits.

PMID- 17039956
TI  - Using ultrasonic technology to manufacture products.
AB  - The use of ultrasonics in medical device manufacturing is gaining momentum as
      designers and engineers take advantage of the benefits it offers. A number of
      example medical applications are described that demonstrate the utility of
      ultrasonic processing in their manufacturer.

PMID- 17039957
TI  - Biosensing in California.
AB  - Worldwide sales of medical biosensors now exceed pounds 2.8 billion (Euro 4.1
      billion) per annum and applications of biosensing technology are highly relevant
      to United States homeland security. A recent mission funded by the United Kingdom
      government to California, USA, investigated some of the development work going on
      there.

PMID- 17039958
TI  - Achieving effective component placement.
AB  - Greater use of electronics assemblies, a decrease in product size and increased
      complexity are placing new demands on placement systems.

PMID- 17039959
TI  - The medical device industry in Italy.
AB  - Important changes have been taking place in Italy, particularly in the areas of
      enforcement of the medical device Directives and reimbursement. An update on
      these developments and news on the industry in Italy are provided here.

PMID- 17039960
TI  - Meeting the challenges in Italy.
AB  - Companies in the dynamic biomedical district of Mirandola are finding success in
      the new strategies they are adopting. This article reviews their challenges and
      initiatives.

PMID- 17039961
TI  - Implantable PEEK extends the options.
AB  - The availability of a performance polymer alongside the established metals and
      ceramics for orthopaedic applications offers more choice and capabilities.

PMID- 17039962
TI  - Giving patients the choice of home therapy.

PMID- 17039963
TI  - Setting quality measures for dialysis in SNFs.

PMID- 17039964
TI  - Dialysis Facility Compare: A consumer choice tool gets better.

PMID- 17039965
TI  - Making things work (successfully) in hospital-based dialysis.

PMID- 17039966
TI  - Understanding software license and services agreements.

PMID- 17039967
TI  - Use of the NxStage system one for daily home hemodialysis.

PMID- 17039968
TI  - Dialysis: A love/hate relationship? Interview by Courtney Stuempges.

PMID- 17039969
TI  - The Northwest Kidney Centers' experience with the Aksys PHD system.

PMID- 17039970
TI  - Dialyzing at home with the 2008K.

PMID- 17039971
TI  - Document it!

PMID- 17039972
TI  - Lessons learned--one facility's experience with venturing into the home
      hemodialysis market.
AB  - The home hemodialysis program team at Community/ Physicians Dialysis Center
      Fairborn began training their first patient in October 2004. They now have six
      home patients dialyzing using either daily nocturnal or short daily home
      hemodialysis. Improved patient outcomes, including excellent morbidity/mortality
      figures, are hallmarks of the success of the. program. In addition, all home
      patients have seen moderate to large improvements in quality of life since
      starting to dialyze at home. This article describes the details involved with
      developing the program, and what was learned along the way. It is the hope of
      this author that others will be encouraged by this story, and embrace the
      challenge of providing this exciting modality option to the patients they serve.

PMID- 17039974
TI  - Clinical semiology of neuromuscular diseases (2).

PMID- 17039973
TI  - Why we need the option of more dialysis.

PMID- 17039975
TI  - Readthrough strategies for stop codons in Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy is due to mutations of the dystrophin gene. These are
      large deletions or duplications in 80% of cases, while premature stop codons
      (nonsense point mutations) account for 7% of cases. This subgroup of patients may
      take advantage of the properties of the antibiotic gentamicin to suppress stop
      codons (readthrough). The efficiency of the readthrough varies inversely to the
      efficiency of a stop codon and is also affected by the different components of
      the drug. Following gentamicin treatment of mdx mice, dystrophin was re-expressed
      up to 20% of normal level, albeit with variability among animals. Human trials
      with gentamicin have so far obtained doubtful results. PTC124 belongs to a new
      class of small molecules that mimics at lower concentrations the readthrough
      activity of gentamicin. The administration of PTC124 resulted in the production
      of full-length and functionally active dystrophin both in vitro and in mdx mice.
      A Phase II clinical trial is now in course and will be terminated at the end of
      2006.

PMID- 17039976
TI  - Parkin and its association with alpha-synuclein and AbetaPP in inclusion-body
      myositis and AbetaPP-overexpressing cultured human muscle fibers.
AB  - Parkin, an E3-ubiquitin ligase in the ubiquitin-proteasome system, facilitates
      degradation of alpha-synuclein and other proteins. Since ubiquitinated
      multiprotein-aggregates containing amyloid-beta (Abeta), alpha-synuclein, and
      other proteins, are characteristic of sporadic inclusion-body myositis (s-IBM)
      muscle fibers, we asked whether parkin might have a role in s-IBM pathogenesis.
      We studied the association of parkin with alpha-synuclein and Abeta-precursor
      protein (AbetaPP) in s-IBM muscle biopsies and in our IBM model based on
      overexpression of AbetaPP into cultured human muscle fibers. We report the
      following in s-IBM muscle fibers: a) parkin was increased 2.7 fold and
      accumulated in aggregates also containing Abeta and alpha-synuclein; b) alpha
      synuclein was increased 6.3 fold; c) parkin physically associated with alpha
      synuclein and AbetaPP; d) alpha-synuclein and AbetaPP were ubiquitinated. In the
      IBM model: a) parkin was increased 2.7 fold, b) it associated with alpha
      synuclein and AbetaPP. CONCLUSION: 1. This is the first demonstration that in a
      human muscle disease alpha-synuclein associates with parkin, and might be
      ubiquitinated by it. 2. The small increase of parkin relative to the much larger
      increase of alpha-synuclein might be insufficient to secure complete
      ubiquitination and consequent degradation of alpha-syn. 3. AbetaPP might be a
      novel substrate of parkin.

PMID- 17039977
TI  - Italian guidelines for molecular analysis in myotonic dystrophies.
AB  - Myotonic dystrophies, the most common form of adult muscular dystrophy, comprise
      at least two forms, clinically and genetically heterogeneous. Myotonic dystrophy
      type 1 and type 2 are both caused by unstable repetitions in untranslated gene
      regions: a [CTG]n expansion in the 3' region of the DMPK gene on chromosome 19q13
      (DM1) and [CCTG]n tetranucleotide repeat located in the first intron of the ZNF9
      gene on chromosome 3q21 (DM2). DM clinical features are caused by a gain of
      functions RNA mechanism in which the CUG and CCUG repeats alter nuclear
      functions, including alternative splicing of shared genes. Southern blot and/or
      polymerase chain reaction PCR-based approaches allow the detection of DM
      mutations in almost 100% of cases, however, the expansion size and the elevated
      grade of somatic instability make molecular testing for DM a diagnostic
      challenge. The increased use of DNA testing for DM generates many questions
      regarding the indications and interpretations of the test which require
      standardized methods, routinely available in molecular genetic laboratories.
      Here, we propose Guidelines for the molecular diagnosis of DM1 and DM2 approved
      by the Italian Ministry of Health in 2005 (Piano Nazionale Linee Guida, PNLG).
      Best practice for DM molecular analysis in diagnostic application, presymptomatic
      and prenatal testing, using direct and indirect approaches are described, with
      particular attention focused on ethical, legal and social issues. Overviews of
      materials used in the molecular diagnosis, as well as internet resources, are
      also included.

PMID- 17039978
TI  - Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation
      in the GDAP1 gene.
AB  - Mutations in the ganglioside -induced differentiation-associated protein 1
      (GDAP1) gene are common a cause of the Charcot-Marie-Tooth (CMT4A) disease with
      autosomal recessive mode of inheritance. To date more than twenty mutations in
      the GDAP1 gene have been reported in patients suffering from the demyelinating,
      axonal or mixed form of Charcot-Marie-Tooth disease. Only in a few CMT4A affected
      patients sural nerve biopsy findings have been provided. We report a homozygous
      Leu239Phe mutation in the GDAP1 gene in a 39-year-old female with a severe form
      of mixed axonal and demyelinating Charcot-Marie-Tooth disease.

PMID- 17039979
TI  - Tumor-like brain lesions in a patient with Hashimoto encephalopathy and
      hereditary motor and sensory neuropathy.

PMID- 17039980
TI  - Exon skipping with U7 gene transfer.

PMID- 17039981
TI  - Predictors of death within six months in patients with advanced AIDS.
AB  - OBJECTIVES: This study sought to identify potential predictive variables of death
      within 6 months in patients with advanced AIDS. METHODS: Investigators enrolled a
      consecutive series of patients with advanced AIDS admitted to a skilled nursing
      facility in New York City over a 1-year period. Demographic, clinical,
      laboratory, and outcome data were abstracted from medical records using a
      standardized data collection instrument. RESULTS: Of the 152 patients enrolled
      during the study period, 61 patients (40%) died within 6 months from date of
      admission. Serum albumin, percent deviation from ideal body weight, and number of
      comorbidities at the time of admission proved to be the best combination of
      predictors of death within 6 months. SIGNIFICANCE OF RESULTS: The decrease in
      AIDS mortality over the past decade, along with an increase in prevalence due to
      longer survival, has been attributed primarily to the successful use of highly
      active antiretroviral therapy (HAART). HAART regimens, however, can also produce
      both short-term adverse effects and long-term complications. The prognostic model
      developed by this study may be useful in guiding treatment decisions in patients
      with advanced AIDS for whom a more palliative care plan may be sought.

PMID- 17039982
TI  - A pilot examination of the impact of cancer patients' fatigue on their spousal
      caregivers.
AB  - OBJECTIVE: In this pilot project we examined the quality of life of spouses of
      cancer patients who had significant fatigue. METHODS: We assessed both the
      spouses of cancer patients and the patients who presented with chemotherapy
      induced fatigue and anemia. Study endpoints included the impact that cancer
      patients' fatigue had on their spouses' quality of life, including their own
      levels of fatigue, depressive symptoms, activity levels, work absenteeism, and
      marital adjustment. We examined the extent to which changes in patients' fatigue
      from baseline to one month follow-up were associated with changes in spouses'
      quality of life indices. RESULTS: 25 couples completed the study. Seven (28%)
      spousal caregivers reported handling fewer responsibilities at work, 8 (32%) had
      reduced their work hours, and 8 (32%) felt that they were less effective overall
      at work. Spousal caregivers also missed a significant amount of time at work
      during the month long study, missing an average of 2.7 (SD = 2.95) days, with an
      additional 1.29 (SD = 2.97) sick days and 1.76 (SD = 2.63) vacation days during
      that time. Spouses reporting greater levels of caregiver strain were more likely
      to have increased fatigue at baseline (F1,23 = 8.11, p < .01), and worse dyadic
      adjustment at both time points (baseline: F1,23 = 7.80, p < .01; follow-up: F1,21
      = 9.24, p < .01). Also, those with more caregiver strain were less likely to
      engage in social activity at baseline (F1,23 = 6.11, p < .05) and more likely to
      engage in less work by the one month follow-up (F1,20 = 8.36, p < .01).
      SIGNIFICANCE OF RESULTS: Spouses who were identified as having elevated burden
      experienced more personal fatigue, had worse dyadic adjustment, reported poor
      energy levels, and tended to engage in fewer work and social activities; the
      impact of patient's fatigue level on these parameters was highly variable in this
      small pilot study.

PMID- 17039983
TI  - Are palliative cancer patients willing and able to participate in a physical
      exercise program?
AB  - OBJECTIVE: The primary aim of the present article was to identify palliative care
      patient populations who are willing to participate in and able to complete a
      group exercise/physical training program designed specifically for the individual
      patient. METHOD: We conducted a prospective phase II intervention study examining
      the willingness and ability of palliative care cancer patients to participate in
      a group exercise physical training program. Patients who were diagnosed with
      incurable cancer and had a life expectancy of less than 1 year at two outpatient
      clinics were invited to participate in an exercise program in the hospitals. The
      groups met twice a week over a 6-week period. RESULTS: One hundred one
      consecutive patients were asked for inclusion. Sixty-three patients agreed to
      participate. Sixteen (25%) of the 63 patients dropped out after consent was
      given, but before the program started due to medical problems, social reasons, or
      death. Thus, 47 patients started the exercise program. Thirteen patients withdrew
      during the program due to sudden death, medical problems, or social reasons. The
      most frequent reasons for withdrawal were increased pain or other symptoms.
      Thirty-four patients completed the exercise program. SIGNIFICANCE OF RESULTS: A
      high proportion of incurable cancer patients were willing to participate (63%) in
      a structured exercise program. The attrition rate was high, but despite being
      severely ill, 54% of the patients completed the exercise period. This shows that
      a physical exercise program tailored to the individual patient is feasible in
      this population.

PMID- 17039984
TI  - Patient desires: a model for assessment of patient preferences for care of severe
      or terminal illness.
AB  - OBJECTIVE: Patient-centered care is better achieved through a comprehensive
      understanding of patients' preferences for how they want to live their life and
      how they want to influence their own death. Though much has been written on
      identifying goals of care, it is often difficult for clinicians to articulate
      patient goals to guide care planning. We explored the literature on patient's
      preferences for their care in chronic or life-limiting illness to develop a model
      for assessment of patient perspectives. We then illustrated our model with
      composite patients from our clinics and we provide questions to guide patient
      discussion. METHODS: We searched MEDLINE from 1986 to 2004 for primary research
      articles that relate primarily to a patient's preferences for his or her care. We
      reviewed over 3500 titles, abstracts, and research papers. Hundreds of articles
      described patients' quality of life, health status, or satisfaction. We excluded
      consensus guidelines, non-English papers, reviews, and articles focused on
      medical professional perspectives. Forty-eight studies focused primarily on
      patient preferences. Using an iterative process, we identified unique issues and
      broader themes in patients' desires for their care. RESULTS: Studies focused on
      patients with cancer, those in hospice or those with terminal disease. Three
      domains emerged: patient feelings about disease, feelings about suffering, and
      feelings about the circumstances of death. Attention was given to the differences
      between patients in terms of the strength and persistence of feelings in each
      domain. SIGNIFICANCE OF RESULTS: Based on existing data, there are three
      fundamental domains of patient perspective that influence preferences for care.
      These domains can be assessed by the care team to guide the development of a plan
      of care and to identify areas of conflict. Our review identifies gaps in the end
      of-life literature and areas for future work in patient preferences.

PMID- 17039985
TI  - Pain management and related factors in advanced cancer patients who initiated
      opioid therapy in an outpatient setting.
AB  - OBJECTIVE: The aim of this study was to clarify the state of pain management in
      Japanese patients with advanced cancer who initiated opioid therapy in an
      outpatient setting. METHODS: Interview surveys using questionnaires were
      conducted and medical records were reviewed. Pain relief was defined as >33%
      decrease in worst pain intensity score, and significance of early pain relief was
      investigated in terms of changing self-efficacy for activities of daily living
      (ADL). Factors related to early pain relief were also investigated. RESULTS: The
      study was conducted between June and December 2003, on 20 patients (13 women, 7
      men; mean age, 59 years). Compared to score at initiation of opioid
      administration (Numerical Rating Scale, 8.3 +/- 1.3), pain relief was generally
      insufficient at 2 weeks (early pain relief ratio was only 42%). Patients with
      sufficient pain relief at 2 weeks displayed significant improvements in numerous
      ADL functions and symptom-coping efficacy (p = 0.037), confirming the importance
      of early pain relief. Early pain relief was associated with high frequency of
      hospital visits before opioid administration and absence of sudden excavation
      within the first 2 weeks. SIGNIFICANCE OF RESULTS: Result of this study indicated
      insufficient pain relief at an outpatients setting with advanced cancer patients.
      In the meantime, patients had who their pain decrease after 2 weeks also had
      improved ADL and self-efficacy at the same time. These findings suggest that to
      achieve early pain relief in an outpatient setting, clinical staff must assess
      pain earlier and inform patients of possible breakthrough pain following opioid
      administration and available treatments for such occurrences.

PMID- 17039986
TI  - Methadone in the treatment of pain and terminal delirum in advanced cancer
      patients.
AB  - OBJECTIVE: This prospective study documents the use of methadone as part of an
      opioid rotation strategy in patients with uncontrolled pain and severe delirium
      admitted for terminal care to a tertiary cancer palliative care hospital.
      METHODS: We reviewed the treatment of 20 patients with severe pain and delirium
      at the end of life who's delirium did not improve 24 h or longer after starting a
      neuroleptic medication. RESULTS: Ten male and 10 female patients, 47 to 77 years
      old, were rotated or "switched" to methadone due to uncontrolled pain in the
      setting of delirium, limiting further opioid dose escalation. At 2 weeks, a total
      of 10 patients had expired. Of the 10 patients who were alive 2 weeks after
      starting methadone, 7 patients were stable on an average of 1.1 mg/h methadone, 2
      patients were restarted on morphine IV and one on Percocet. The calculated
      average equianalgesic dose of methadone was 9% (2%-17%) of the previous morphine
      equivalent dose. Of the 20 patients who were switched to methadone for what
      appeared to be terminal delirium, the pain control was significant in 15,
      moderate in 3, and unchanged in 2 patients. Average analgesia was good to
      excellent (average Numeric Analog Scale rating [NAS] decreased from 8.2 to 2.5).
      Sedation had decreased from 1.65 to 0.55 on a scale of 0 to 3. Of the 20
      patients, improvement of cognitive status was significant in 9, moderate in 6,
      partial in 2, and none in 3 patients. The Memorial Delirium Assessment Scale
      (MDAS) showed improvement from an average of 23.6 prior to the switch to 10.6 3
      days after. Decreased alertness on methadone was devoid of agitated features.
      SIGNIFICANCE OF RESULTS: Our study suggests that methadone can be effective in
      the treatment of both refractory pain and what appears to be terminal delirium.
      Most patients in our group had at least a short-term improvement in mental status
      as well as significant and lasting improvement in analgesia.

PMID- 17039987
TI  - Clinical assessment of depression in terminally ill cancer patients: a practical
      guide.
AB  - Depression is commonly experienced by cancer patients at the end of life. The
      identification of patients suffering from depression is essential to provide
      clinicians with an opportunity to relieve considerable suffering. However, the
      assessment of depressive symptoms is complex and often challenging in a
      terminally ill cancer population. This article offers practical guidelines to
      assist clinicians with the diagnosis of depression, reviews the defining symptoms
      of depression and their unique presentation in patients at the end of life,
      suggests modifications of the standard diagnostic interview, and provides
      examples of specific assessment questions to target depressive symptoms at the
      end of life.

PMID- 17039988
TI  - Caring for those who care for the dying: coping with the demands on palliative
      care workers.
AB  - The article reviews the complex and demanding field of palliative care, noting
      the sources of the stresses and strains that the health care workers often
      encounter. It illustrates the multidimensional needs of patients, the reasons why
      they and/or their families may hamper palliative care, and, mostly, what can be
      done to deal with and-better yet-prevent palliative workers' burnout.

PMID- 17039989
TI  - Development of Wernicke encephalopathy in a terminally ill cancer patient
      consuming an adequate diet: a case report and review of the literature.
AB  - Malignancy-associated primary thiamine deficiency has been documented in several
      experimental tumors, clinical case reports, and in patients with fast growing
      malignancies. We report a terminally ill cancer patient who developed delirium.
      Close examination of the patient demonstrated that delirium was caused by
      thiamine deficiency, although she had been consuming an average of 990 cal/day
      for the past 3 weeks. Malabsorption or consumption by the tumor was considered
      the mechanism of thiamine deficiency. Early recognition and subsequent treatment
      resulted in successful palliation of delirium. In terminally ill cancer patients,
      clinicians must remain aware of the possibility of Wernicke's encephalopathy,
      when the patients develop unexplained delirium, even if the patient has been
      consuming adequate amounts of food. Early intervention may correct the symptoms
      and prevent irreversible brain damage, and the quality of life for the patient
      may improve.

PMID- 17039990
TI  - Wernicke encephalopathy presented in the form of postoperative delirium in a
      patient with hepatocellular carcinoma and liver cirrhosis: a case report and
      review of the literature.
AB  - OBJECTIVE: Although Wernicke encephalopathy has been reported in the oncological
      literature, it has not previously been reported in postoperative cancer patients.
      METHODS: In this communication, we report a patient of hepatocellular carcinoma
      with liver cirrhosis who developed Wernicke encephalopathy in the form of
      postoperative delirium. Preoperatively, the patient had a very good appetite and
      had eaten all the food of an 1800 cal/day diet until 1 day before operation. The
      operation was done without any complications. The patient developed delirium 2
      days after the lobectomy of the liver. The level of delirium remained unchanged
      until administration of thiamine starting on day 7 postoperatively, which
      resulted in palliation of delirium without brain damage. Laboratory data
      demonstrated that the serum thiamine level at day 6 postoperatively was below the
      lower limit of normal. As the mechanism of Wernicke encephalopathy, we thought
      that decreased ability to store thiamine due to liver cirrhosis led to depletion
      of thiamine faster than had been expected. RESULTS AND SIGNIFICANCE OF THE
      RESEARCH: In cancer patients, clinicians must always remain aware of the
      possibility of Wernicke encephalopathy, especially in patients with liver
      dysfunction, which decreases the ability to store thiamine in the liver. Early
      detection and intervention may alleviate the symptoms of delirium and prevent
      irreversible brain damage.

PMID- 17039991
TI  - Nursing practice models: time for change.

PMID- 17039992
TI  - Sabbatical journey of discovery: recruitment, retention and quality of work life.

PMID- 17039993
TI  - Wendy S. Hill.

PMID- 17039994
TI  - Health Outcomes for Better Information and Care (HOBIC): integrating patient
      outcome information into nursing undergraduate curricula.
AB  - Nursing-sensitive outcomes provide common information across sectors, thus
      eliminating duplication that frequently occurs as individuals move across
      settings. These outcomes also facilitate increased trust among colleagues and
      support common understandings of patient care needs, thus enhancing continuity of
      care. Outcomes-oriented information is also likely to increase patient safety and
      improve overall quality of care. Shared standards and data support consistent
      decision-making, as nursing decisions can be tracked back over time to assess
      patient care outcomes. Consequently, nurses will have the means to determine the
      impact of their interventions on patient outcomes. At the same time, adoption of
      common approaches to patient assessment leads to greater professional
      accountability and moves nursing care from a task orientation to an outcomes
      focus. For administrators, such improvements in monitoring and evaluating patient
      outcomes translate into improvements in efficiencies and effectiveness, thus
      providing a return on investment in implementing these outcomes within their
      agency. For nurses, integration and utilization of outcomes information increases
      the visibility and significance of their decision-making and patient care.
      Together with patients, nurses can utilize the outcomes information to make
      evidence-based decisions and advocate for appropriate care. At an aggregate
      level, the use of outcomes information creates a continuous feedback loop that is
      essential to ensuring evidence-based care and the best possible patient outcomes,
      not only for individuals, but also for families, communities and populations.
      Outcomes-oriented care provides a gateway for transforming the way we care for
      patients; puts safe, ethical, high-quality care for patients first; embodies the
      principles of evidence-based practice; ensures that the value of nursing is
      clearly understood within the larger system; and ensures that the requirements
      for measurability and accountability can be achieved. This journey is continuous
      and is being expanded to engage all other health disciplines in understanding and
      documenting their contributions to patient care, both as individual practitioners
      and as members of a healthcare team. Preparing nursing students in an outcomes
      approach will facilitate systemwide adoption of HOBIC patient outcomes over time
      and provide a means to determine the impact of nursing care on our patients.

PMID- 17039995
TI  - Case study: on the leading edge of new curricula concepts: systems and safety in
      nursing education.
AB  - The Nursing Division of the Saskatchewan Institute of Applied Science and
      Technology (SIAST) first included systems and patient safety as a priority in its
      institutional business and strategic plan in 2003. Three interrelated leading
      edge, two-year projects (2004-2006) were launched: Best Practice, Mentorship and
      Patient Safety, with the intent that each project would enhance the others. This
      case study focuses on the work of the Patient Safety Project Team. The team
      developed a project framework and strategic plan, conducted a literature review
      and identified key concepts related to systems and patient safety. Strategies to
      integrate these concepts into the school's 15 nursing education programs are
      being implemented.

PMID- 17039996
TI  - Workplace empowerment, work engagement and organizational commitment of new
      graduate nurses.
AB  - As a large cohort of experienced nurses approaches retirement, it is critical to
      examine factors that will promote the engagement and empowerment of the newer
      workforce, allowing them to provide high quality patient care. The authors used a
      predictive, non-experimental survey design to test a theoretical model in a
      sample of new graduate nurses. More specifically, the relationships among
      structural empowerment, six areas of work life (conceptualized as antecedents of
      work engagement), emotional exhaustion and organizational commitment were
      examined. As predicted, structural empowerment had a direct positive effect on
      the areas of work life, which in turn had a direct negative effect on emotional
      exhaustion. Subsequently, emotional exhaustion had a direct negative effect on
      commitment. Implications of these findings for nursing administrators are
      discussed.

PMID- 17039997
TI  - Nurses' perceptions of medication safety and medication reconciliation practices.
AB  - Medication reconciliation (MR) involves the accurate transfer of medication
      information across the continuum of care. The aim of this study was to measure
      nurses perceptions of patient safety, medication safety and current MR practice
      at transition points in a patient's hospital stay. Surveys were distributed to
      111 nursing staff in three general medicine units at Capital Health District,
      Nova Scotia, in August 2005. A total of 39 nurses (35% response rate) completed
      the survey. "Teamwork within units" was the safety culture dimension with the
      highest positive response (98.1%), while the processes of handoffs and
      transitions received the lowest positive response (42.8%). Key areas identified
      for improvement relative to the current level of MR practice include
      institutional patient safety systems (e.g., low confidence in existing systems
      and procedures), inconsistent practices (e.g., wide variation in whether
      community pharmacists are contacted to verify medication profiles), lack of
      communication (e.g., between healthcare professionals) and staffing resources
      (e.g., MR is perceived as a very time-consuming process). Addressing these
      challenges prior to implementing a formalized MR program should help to ensure
      success of the project. The insights gained through the use of this survey may
      prove valuable to other Canadian healthcare organizations that are implementing
      MR services.

PMID- 17039998
TI  - Magnet hospital characteristics and northern Canadian nurses' job satisfaction.
AB  - Retention of health professionals is a serious problem in northern and rural
      Canada. Magnet hospital factors are known to increase job satisfaction, which
      contributes to retention. The purpose of this paper is to examine the extent to
      which magnet hospital characteristics (management support, nurse-doctor and nurse
      manager relationships, professional autonomy and responsibility) contribute to
      northwestern Canadian hospital nurses' job satisfaction. Participants were 123
      nurses from 13 hospitals in western Canada. They completed a survey and
      structured interview that provided data on their attitudes and perspectives about
      their hospital jobs. We found that some magnet hospital characteristics apply in
      northern and rural western Canadian hospitals. Our findings indicate that
      management support and nurse-manager relations are important to nurses' job
      satisfaction, but participants' views of management were fairly negative, an
      issue that management needs to address. Nurses' ability to work professionally
      and autonomously is also important to their satisfaction. There are indications
      that nursing supervisory skill sets need to be upgraded in some instances.

PMID- 17039999
TI  - Words matter: a proposed nosologic lexicon for sleep breathing.

PMID- 17040000
TI  - Neurobehavioral morbidity associated with disordered breathing during sleep in
      children: a comprehensive review.
AB  - STUDY OBJECTIVES: To comprehensively review research on the association between
      childhood sleep-disordered breathing (SDB) and neurobehavioral functioning.
      DESIGN: Qualitative and quantitative literature review. SETTING: N/A. PATIENTS OR
      PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The findings of
      61 studies of the relationship between childhood SDB and neurobehavioral
      functioning were critically evaluated and synthesized. There is strong evidence
      that childhood SDB is associated with deficits in behavior and emotion
      regulation, scholastic performance, sustained attention, selective attention, and
      alertness. There is also evidence that SDB has minimal association with a child's
      typical mood, expressive language skills, visual perception, and working memory.
      Findings have been insufficient to draw conclusions about intelligence, memory,
      and some aspects of executive functioning. Mechanisms by which SDB might result
      in neurobehavioral morbidity are being explored, but clinical symptoms such as
      chronic snoring remain the best predictors of morbidity. Short-term SDB treatment
      outcome studies are encouraging, but the long-term outcomes are not known.
      Failing to treat SDB appears to leave children at risk for long-term
      neurobehavioral deficits. CONCLUSIONS: Childhood SDB is associated with
      neurobehavioral morbidity. Applying commonly used guidelines for causal
      inference, even in the absence of a much-needed randomized clinical trial, there
      is strong evidence of association, consistent findings, and specificity of
      effect. There is suggestive evidence that this association fits the expected
      temporal pattern and that SDB is a biologically plausible cause of
      neurobehavioral deficits. Clinicians should be alert to the coexistence of SDB
      symptoms and concerns about a child's academic progress, attention, arousal, or
      behavior or emotion regulation.

PMID- 17040001
TI  - An epidemiologic study of sleep-disordered breathing symptoms among adolescents.
AB  - STUDY OBJECTIVES: To examine the prevalence and distribution of the symptoms of
      sleep-disordered breathing (SDB) in a community-based sample of adolescents, and
      to assess association of SDB with body mass index, daytime sleepiness, school
      performance, and attention-deficit/hyperactivity disorder. DESIGN: Epidemiologic
      study of a community-based sample of adolescents and 1 parent with whom separate
      structured face to face diagnostic interviews were conducted. SETTING:
      Metropolitan Detroit, Michigan, USA. PARTICIPANTS: One thousand fourteen
      adolescents aged 13 to 16 years and a paired parent. MEASURES AND RESULTS: SDB
      was defined as report of loud snoring, gasping/choking or snorting, awakening
      with gasping or choking, or momentary periods of stopped or abnormal breathing
      occurring weekly. More than 20% of the adolescents snored at least a few nights
      per month, 6% snoring every or nearly every night. Apnea-like symptoms affected
      from 2.5% to 6.1% of adolescents. The prevalence of weekly SDB was 6.0% according
      to both adolescent and parental report and was twice as likely among African
      Americans as Caucasians. The association of body mass index with SDB was twice as
      great among Caucasian adolescents as African American adolescents. SDB was
      independently associated with excessive daytime sleepiness, poorer grade point
      averages, and attention-deficit/hyperactivity disorder-inattention type; each
      being more than twice as likely to occur among those with SDB than those without
      SDB. CONCLUSIONS: Symptoms of SDB appear to be common among adolescents and
      independently associated with short- and longer-term adverse outcomes. These
      associations appear to be complex in the population and will require longitudinal
      epidemiologic studies to clarify the nature of their relationships and the
      opportunities for intervention.

PMID- 17040002
TI  - Bruxism in children: effect on sleep architecture and daytime cognitive
      performance and behavior.
AB  - STUDY OBJECTIVES: Sleep bruxism is an involuntary mandibular movement with tooth
      grinding during sleep. The prevalence of sleep bruxism in children is high and
      may lead to frequent arousals with altered daytime functioning. We investigated
      the sleep architecture, the incidence of gastroesophageal reflux, and the daytime
      cognitive behavioral functioning in a group of children with sleep bruxism.
      DESIGN-PATIENTS: This prospective pilot study included 10 children.
      Polysomnographic data with pH-probe analysis was compared with 10 age- and sex
      matched controls. Each patient completed a dental evaluation, a nighttime
      polysomnogram, and cognitive behavioral tests (Kaufman Brief Intelligence Test
      and Achenbach Child Behavior Checklist). RESULTS: Eight of 10 children had
      clinically significant bruxism and the 2 remaining patients had recent teeth
      exfoliation. There was no difference on sleep architecture between patients and
      controls, except for a higher arousal index for the bruxism group (36.7 vs 20.7,
      p < .007). Sleep bruxism occurred more frequently in stage 2 and rapid eye
      movement sleep, with arousals in 66% of the cases. There was no relationship of
      bruxism to gastroesophageal reflux or intelligence. However, 40% of the patients
      had elevated scores on the Achenbach Child Behavior Checklist, indicating
      significant attention and behavior problems, and there were moderate correlations
      between the arousal index and several of the behavior-problem scales from the
      Achenbach Child Behavior Checklist (0.5 to 0.6). CONCLUSIONS: The data suggest
      that children with bruxism have a higher arousal index, which may be associated
      with an increased incidence of attention-behavior problems. Future studies
      investigating pediatric sleep bruxism will need to focus on behavior issues that
      may be prevalent in this population.

PMID- 17040003
TI  - Recommendations for a standard research assessment of insomnia.
AB  - STUDY OBJECTIVES: To present expert consensus recommendations for a standard set
      of research assessments in insomnia, reporting standards for these assessments,
      and recommendations for future research. PARTICIPANTS: N/A. INTERVENTIONS: N/A.
      METHODS AND RESULTS: An expert panel of 25 researchers reviewed the available
      literature on insomnia research assessments. Preliminary recommendations were
      reviewed and discussed at a meeting on March 10-11, 2005. These recommendations
      were further refined during writing of the current paper. The resulting key
      recommendations for standard research assessment of insomnia disorders include
      definitions/diagnosis of insomnia and comorbid conditions; measures of sleep and
      insomnia, including qualitative insomnia measures, diary, polysomnography, and
      actigraphy; and measures of the waking correlates and consequences of insomnia
      disorders, such as fatigue, sleepiness, mood, performance, and quality of life.
      CONCLUSIONS: Adoption of a standard research assessment of insomnia disorders
      will facilitate comparisons among different studies and advance the state of
      knowledge. These recommendations are not intended to be static but must be
      periodically revised to accommodate further developments and evidence in the
      field.

PMID- 17040004
TI  - Attenuated thermoregulatory response to mild thermal challenge in subjects with
      sleep-onset insomnia.
AB  - STUDY OBJECTIVES: To determine if heat loss capacity of sleep onset insomniacs
      was different from that of healthy sleepers. DESIGN: Measure skin temperature
      responses following brief exposure to a warm peripheral thermal challenge (PTC).
      SETTING: Sleep research laboratory in South Australia. PARTICIPANTS: Eight
      primary insomniacs with sleep onset insomnia according to DSM-IV-TR criteria
      (SOI; 5 male, 3 female; mean age +/- SEM = 35.2 +/- 4.2 years) and ten healthy
      sleeping control subjects (HS; 7 male, 3 female; mean age = 28.2 +/- 2.8 years).
      INTERVENTIONS: Two PTC conditions in counterbalanced order on non-consecutive
      days. During each condition, the subject's non-dominant forearm and hand were
      immersed for 3 minutes in Warm (45 degrees C) or Control water (i.e. same as the
      subject's non-dominant index finger temperature just prior to immersion, range 30
      35 degrees C). MEASUREMENTS AND RESULTS: HS had a significantly higher maximum
      finger temperature response after immersion than SOI (P < 0.05). Expressed
      relative to Control PTC temperatures, the Warm PTC caused a significant increase
      in mean finger temperature for HS of 4.1 +/- 0.8 degrees C, compared with SOI of
      0.9 +/- 0.4 degrees C. A significant negative relationship was observed between
      maximum finger temperature response and self-reported sleep onset latencies (R = 
      0.57, P < 0.05). There were no main effects of sleep status (SOI vs. HS) or
      interactions by time, in skin temperatures measured at either the back of hands
      or feet. CONCLUSIONS: SOI were observed to have significantly attenuated
      thermoregulatory responses to a mild positive thermal challenge, providing
      evidence that impaired heat loss capacity from the periphery is associated with
      sleep onset insomnia.

PMID- 17040005
TI  - PLMS and PLMW in healthy subjects as a function of age: prevalence and interval
      distribution.
AB  - STUDY OBJECTIVES: Several studies have demonstrated a positive correlation
      between periodic leg movements during sleep (PLMS) and age in healthy subjects.
      However, little is known about periodic leg movements during wakefulness (PLMW)
      in this population. Although the definitions of PLMS and PLMW specify a typical
      intermovement interval of 20 to 40 seconds, scoring criteria allow an
      intermovement interval of 4 to 90 seconds. The aim of the present study was to
      look at the prevalence and interval distribution of PLMS and PLMW in relationship
      with age in a population of healthy subjects. DESIGN: Periodic leg movements were
      recorded during 1 night. SETTING: Sleep laboratory, Hopital du Sacre-Coeur de
      Montreal. PARTICIPANTS: Sixty-seven healthy subjects aged between 5 and 76 years
      (32 F, 35 M). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The presence of PLMS
      was rare before the age of 40, but then the index increased dramatically. PLMW
      index was higher in younger subjects compared with middle-aged subjects. Interval
      histograms of PLMS did not revealed a clear peak in younger subjects. With
      advancing age, PLMS interval histograms show a peak around 15 to 35 seconds,
      which is not observed in younger subjects. On the other hand, despite high
      indexes, PLMW interval histograms do not show a clear peak for any age group.
      CONCLUSION: These results illustrate that interval evaluation is an important
      feature of the calculation of periodic movements to discriminate spontaneous
      motor activity from PLMS or PLMW.

PMID- 17040006
TI  - A randomized trial evaluating the effectiveness of sodium oxybate therapy on
      quality of life in narcolepsy.
AB  - STUDY OBJECTIVES: To evaluate the efficacy of sodium oxybate versus placebo to
      improve quality of life in patients with narcolepsy. DESIGN: A multicenter,
      double-blind, placebo-controlled trial. SETTING: Outpatient facility of 42 sleep
      centers in the United States, Canada, and Europe. PARTICIPANTS: Study
      participants were 285 patients with narcolepsy, 16 to 75 years of age, with a
      median Epworth Sleepiness Scale score of 18, a Maintenance of Wakefulness Test
      sleep latency of 9.56 minutes, and experiencing symptoms of narcolepsy, including
      cataplexy and excessive daytime sleepiness with recurrent sleep episodes almost
      daily for at least 3 months at the time of enrollment. INTERVENTIONS: Subjects
      were gradually withdrawn from narcolepsy medications used for cataplexy,
      including antidepressants. Subsequently, participants were randomly assigned to
      receive 4.5, 6.0, or 9.0 g per day of sodium oxybate or placebo taken in two
      equally divided doses upon retiring to bed and again 2.5 to 4 hours later for 4
      weeks during the stable dosing phase. MEASUREMENTS AND RESULTS: The change in
      quality of life following the administration of sodium oxybate was measured with
      the Functional Outcomes of Sleep Questionnaire. The nightly administration of
      sodium oxybate produced significant dose-related improvements in the Total
      Functional Outcomes of Sleep Questionnaire score, as well as in the Activity
      Level, General Productivity, Vigilance, and Social Outcomes subscales.
      CONCLUSIONS: The nocturnal administration of sodium oxybate in patients with
      narcolepsy was associated with statistically significant and clinically relevant
      improvements in functional status, an important component of quality of life.

PMID- 17040007
TI  - Nocturnal overdrive pacing for the treatment of sleep apnea syndrome.
AB  - STUDY OBJECTIVES: We investigated the effect of 1 week of nocturnal overdrive
      pacing (NOP) on the apnea-hypopnea index (AHI) in patients with a chronically
      implanted pacemaker and diagnosed during a screening phase with sleep apnea.
      DESIGN: Randomized, single-blind, crossover study. SETTING: University medical
      centers in Zurich, Switzerland, and Berlin, Germany. PATIENTS: Nineteen patients
      with mild to severe sleep apnea/hypopnea (16 men, mean age = 68.8 +/- 11.4 years)
      participated. The individuals did not suffer from permanent atrial arrhythmia,
      did not use continuous positive airway pressure, and had been implanted with
      atrial or dual-chamber pacemakers. INTERVENTIONS: Nocturnal lower rates were 45
      and 75 beats per minute (bpm) at night for the control and NOP arms,
      respectively, and daytime lower rates were 60 bpm. Subjects were in each arm for
      1 week. MEASUREMENTS AND RESULTS: Heart-rate increase from control (61 +/- 9 bpm)
      to NOP (78 +/- 4 bpm) followed by significant reduction in circulation time (24.6
      seconds control, 20.7 seconds NOP; p = .04) resulted in no significant change in
      AHI (26.8 +/- 17.1/h control, 23.0 +/- 16.7/h NOP; p = .49). Seven subjects
      characterized by a higher hypopnea index, less stage 1 and 2 sleep, and less slow
      wave sleep improved at least 1 AHI severity level with NOP, mainly attributable
      to reduction of hypopneas. CONCLUSION: NOP over a period of 1 week followed by a
      reduction in circulation time did not improve AHI in patients with SA. Whether an
      improvement by 1 AHI severity level in a specific subset of patients reflects a
      true response remains to be elucidated by further studies.

PMID- 17040008
TI  - Complex sleep apnea syndrome: is it a unique clinical syndrome?
AB  - STUDY OBJECTIVES: Some patients with apparent obstructive sleep apnea hypopnea
      syndrome (OSAHS) have elimination of obstructive events but emergence of
      problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this
      sleep-disordered breathing problem, which for the sake of study we call the
      "complex sleep apnea syndrome," are not well characterized. We sought to
      determine the prevalence of complex sleep apnea syndrome and hypothesized that
      the clinical characteristics of patients with complex sleep apnea syndrome would
      more nearly resemble those of patients with central sleep apnea syndrome (CSA)
      than with those of patients with OSAHS. DESIGN: Retrospective review SETTING:
      Sleep disorders center. PATIENTS OR PARTICIPANTS: Two hundred twenty-three adults
      consecutively referred over 1 month plus 20 consecutive patients diagnosed with
      CSA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Prevalence of complex sleep
      apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%,
      respectively. Patients with complex sleep apnea syndrome differed in gender from
      patients with OSAHS (81% vs 60% men, p < .05) but were otherwise similar in sleep
      and cardiovascular history. Patients with complex sleep apnea syndrome had fewer
      maintenance-insomnia complaints (32% vs 79%; p < .05) than patients with CSA but
      were otherwise not significantly different clinically. Diagnostic apnea-hypopnea
      index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/-
      26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous
      positive airway pressure suppressed obstructive breathing, but residual apnea
      hypopnea index, mostly from central apneas, remained high in patients with
      complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea
      syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p < .001). CONCLUSIONS:
      Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS
      until one applies continuous positive airway pressure. They are left with very
      disrupted breathing and sleep on continuous positive airway pressure. Clinical
      risk factors don't predict the emergence of complex sleep apnea syndrome, and
      best treatment is not known.

PMID- 17040009
TI  - Diurnal sex differences in the sleep-wake cycle of mice are dependent on gonadal
      function.
AB  - STUDY OBJECTIVES: Sex is an important determinant of the pathophysiology of
      several disorders that influence and/or impair sleep-wake regulation. To date,
      few studies have examined either the role of sex or the gonadal hormones on sleep
      and wakefulness. The difficulty in performing well-controlled clinical
      experiments on sex and sleep underscores the need for effective animal models to
      investigate the influence of the gonadal hormones on sleep-wake states. This
      study describes the influence of sex on sleep and wakefulness in mice, the
      primary mammalian genetic model for sleep analysis, and tests the hypothesis that
      gonadal function drives sex differences in sleep-wake states. DESIGN:
      Electroencephalogram/electromyogram sleep-wake patterns were recorded in intact
      and gonadectomized male and female C57BL/6J mice maintained on a 14-hour light:10
      hour dark schedule. Following a 24-hour baseline recording, mice were sleep
      deprived during the light phase by gentle handling and given a 10-hour recovery
      opportunity during the immediate dark phase. MEASUREMENTS AND RESULTS: Intact
      female mice spent more time awake than intact males during 24 hours of baseline
      recording at the expense of non-rapid eye movement (NREM) sleep. Though the
      recovery response of NREM sleep was similar between males and females, when
      examined in reference to baseline levels, females exhibited a more robust
      recovery response. Gonadectomy in males and females reduced or eliminated the
      majority of sex differences in sleep architecture and homeostasis. CONCLUSIONS:
      These data demonstrate that the gonadal hormones influence the amount,
      distribution, and intensity of sleep but do not account for all sex differences
      in the sleep-wake cycle.

PMID- 17040010
TI  - Sex differences in sleep: the response to sleep deprivation and restraint stress
      in mice.
AB  - STUDY OBJECTIVES: Numerous clinical studies and sleep surveys have shown
      pronounced sex differences in the occurrence of insomnia and other sleep
      pathologies. It has been suggested that sex differences in sleep, while subtle
      under baseline conditions, may increase in magnitude under biological or
      environmental challenges. However, controlled and experimental studies on sleep
      under challenged conditions rarely include female subjects. In this context, we
      examined sex differences in sleep in the mouse, not only under baseline
      conditions, but also after sleep deprivation and restraint stress. DESIGN: Adult
      male and female C57BL/6J mice were implanted with electrodes to record sleep-wake
      architecture and sleep electroencephalogram under baseline conditions and after 6
      hours of sleep deprivation or 1 hour of restraint stress at the beginning of the
      daily light phase. RESULTS: Although baseline sleep patterns slightly differed
      between the sexes, the homeostatic recovery response to sleep deprivation was
      similar. In contrast, the changes in sleep after restraint stress were markedly
      different between male and female mice, with males displaying a stronger initial
      suppression of sleep and a stronger rebound of rapid-eye-movement sleep later in
      the recovery phase. CONCLUSIONS: In mice, the fundamental homeostatic properties
      of sleep regulation may not differ between the sexes, but the way sleep is
      affected and disrupted by environmental influences may be sex dependent. The
      latter may reflect sex differences in stress sensitivity.

PMID- 17040011
TI  - A reassessment of the hyperphagia/weight-loss paradox during sleep deprivation.
AB  - STUDY OBJECTIVES: Sleep deprivation is a well-known paradigm to investigate the
      deleterious effects of prolonged wakefulness. Previous studies have shown that,
      during sleep deprivation, rats are hyperphagic but, paradoxically, lose body
      weight. This phenomenon has been attributed to increased metabolism. However,
      most previous studies have failed to account for food spillage, which may be
      considerable during sleep deprivation. DESIGN: In the present study, we revisited
      the issue of feeding changes in sleep-deprived rats and introduced different
      procedures to allow accurate estimation of food spillage prior to, during, and
      after 120 hours of sleep deprivation by a single platform technique. SETTING:
      Animal Sleep Research Laboratory, Psychobiology Department, Universidade Federal
      de Sao Paulo, Brazil. MEASUREMENTS AND RESULTS: The main finding was that, once
      corrected for spillage, food intake was not significantly increased during sleep
      deprivation. Increases in food removed from feeders were accompanied by
      proportional increases in food spillage, resulting in no net changes in food
      intake. Further, weight loss did occur during the sleep-deprivation period,
      especially in the first 24 hours, and it was actually explained by a reduction in
      food intake. CONCLUSION: The hyperphagia/weight-loss paradox previously seen
      during prolonged sleep deprivation does not necessarily occur with shorter
      periods of deprivation. Although we found no evidence of hyperphagia for up to 5
      days of sleep deprivation in chow-fed rats, our data suggest that an impairment
      in the ability to increase food intake in response to increased energy
      expenditure contributes to the energy deficit during sleep deprivation in rats.

PMID- 17040012
TI  - Technical innovations and the evolution of endoscopic sinus surgery.
AB  - Since the introduction of endoscopic sinus surgery, a number of significant
      technological advances, as well as an improved understanding of disease
      pathogenesis and management, have enabled major evolutions in surgical
      techniques. Modifications to surgical instruments, imaging, the development of
      the microdebrider, and other newer instrumentation have all contributed to the
      current level of patient success associated with endoscopic intranasal
      techniques. At the same time, it has become evident that anatomic variations are
      less important in the pathogenesis of chronic rhinosinusitis than was previously
      thought, and that ventilation alone is insufficient to resolve well-established
      disease. This paper reviews the changes that have occurred in endoscopic sinus
      surgery over the past 20 years since the techniques were first introduced into
      the United States, and the technologies that have enabled these changes and the
      development of extended endoscopic techniques. Continuing developments of
      interactive computer-guided surgery, endoscopic 3-dimensional imagery, robotics,
      and improved adjunctive therapies will further extend the role of endoscopic
      transnasal approaches to an expanded number of skull base and intracranial
      lesions.

PMID- 17040013
TI  - Frontal sinus surgery: its evolution, present standard of care, and
      recommendations for current use.
AB  - From a historical perspective, frontal sinus surgery has evolved from radical,
      highly invasive, disfiguring approaches to function-preserving, minimally
      invasive, and non-disfiguring intranasal procedures. Most sinus surgeons would
      agree that a sound surgical procedure is one that relieves patients' symptoms and
      provides a safe sinus in which future intracranial and orbital complications will
      not occur. For the future, sinus surgeons are searching for the ideal procedure,
      ie, one that is minimally invasive, reversible, and ensures the patient a safe
      frontal sinus for the long term. The ideal surgery will also leave minimal
      morbidity, will leave no cosmetic defect, and will allow for easy postoperative
      surveillance. To achieve this new standard in frontal sinus surgery, continuous
      refinements are required in the medical management and understanding of the
      disease processes that undermine long-term surgical success. Further advancements
      in instrumentation and visualization techniques are also necessary to enhance
      surgical precision, spare mucosa, and prevent the scarring and neo-osteogenesis
      that may cause surgical failures. Perhaps the most important development may be
      in the selection criteria for appropriate candidates who will benefit most from
      frontal sinus surgery.

PMID- 17040014
TI  - Sinonasal mucociliary clearance in health and disease.
AB  - Although much has been elucidated in the past 170 years concerning the precise
      mechanism of ciliary function in the healthy or diseased human respiratory
      system, significant questions remain. The first description of ciliary action is
      credited to Sharpey in 1835. However, the importance of mucosal function was not
      apparent until Hilding's investigations of the postsurgical canine sinus
      demonstrated scar formation and disruption of mucociliary clearance.
      Subsequently, several techniques for mucosal coverage of exposed bone, most
      notably by Sewall and Boyden, were reported. The underlying physiology explaining
      the importance of the mucosa and the concept of mucosal preservation became
      apparent with the description of the sinonasal mucociliary flow patterns by
      Messerklinger; and thus the restoration of natural sinus physiology, ie,
      mucociliary clearance, became the goal of both medical and surgical treatment of
      sinonasal inflammatory disease. Clearance of benign and pathological substances
      in the mucus is governed by the propulsive force of the beating cilia and the
      physical characteristics of the overlying mucus. The respiratory cilia
      continually beat in a coordinated fashion, and in times of stress (eg, exercise,
      infection, or fever) ciliary beat frequency increases to accelerate mucus
      clearance. Thus, upper airway ciliary motility is under dynamic modulation.
      Multiple investigations incontrovertibly demonstrate a marked decrease in
      sinonasal mucociliary clearance in patients with chronic rhinosinusitis. Possible
      explanations for this finding are 1) a reduced basal ciliary beat frequency, 2)
      an alteration of the viscoelastic properties of airway secretions, and/or 3) a
      blunted dynamic response of sinonasal cilia to environmental stimuli. Studies of
      the first two explanations yield conflicting results, and to date, the third
      possibility remains uninvestigated. A review of the current understanding of the
      cellular regulation of respiratory ciliary activity and its contribution to
      chronic rhinosinusitis is presented.

PMID- 17040015
TI  - Fungus and chronic rhinosinusitis: from bench to clinical understanding.
AB  - Although fungus-related sinusitis has been described for at least 2 centuries, a
      more detailed pathologic description of the problem as it relates to eosinophilic
      disease was not detailed until 1983, when "allergic fungal sinusitis" was
      described histopathologically. Until then, most fungal sinus disease was
      perceived to occur in immunosuppressed diabetic patients with invasive fungus. It
      is now acknowledged that depending upon the immune status of the host, fungus
      related sinus disease can take several forms. Interest in this subject matter was
      intensified in 1999, when it was suggested that fungi might be an important cause
      of most cases of chronic rhinosinusitis. This hypothesis remains controversial,
      and there is mounting evidence to support the multifactorial nature of chronic
      rhinosinusitis, which may include fungus. In fact, etiologic factors for all
      forms of fungus-related sinus disease are still poorly understood. The prevalence
      of the disease and the dominant fungal pathogen appear to vary in different
      geographic regions and probably are related to individual host conditions.
      Immunoglobulin E-mediated allergic reactions to mold appear to be associated with
      disease in some patients, but not in all. Although antifungal therapy is known to
      be lifesaving for invasive disease, its role in extramucosal disease is less well
      defined. Preliminary trials suggest that some systemic and topical antifungal
      agents are of clinical benefit in extramucosal disease. Since sinus fungi are
      rarely invasive in immunocompetent individuals, it is not clear whether the
      effects of the antifungal treatments are a result of the antifungal action
      itself, or due to additional properties these drugs possess. This review
      summarizes the available data and presents some of our clinical and experimental
      findings as to the role of fungus in chronic rhinosinusitis.

PMID- 17040016
TI  - Bacterial biofilms in chronic rhinosinusitis.
AB  - Chronic sinusitis is a prevalent, debilitating condition, and a subpopulation of
      patients fails to respond to either medical or surgical intervention. Bacterial
      biofilms are 3-dimensional aggregates of bacteria that have special properties
      due to their group structure, including increased resistance to antibiotics in
      some forms. They have been shown to play a major role in many chronic infections,
      including cystic fibrosis, endocarditis, and otitis media. Evidence now suggests
      that they may play an important role in chronic sinusitis. Our laboratory has
      identified the presence of biofilms in sinonasal mucosa isolated from human
      patients and on stents removed after frontal sinus surgery. In addition, biofilms
      have been found on the sinus epithelium of rabbits infected with Pseudomonas
      aeruginosa, but not in rabbits infected with non-biofilm-forming P. aeruginosa
      mutants. This animal model can provide opportunities to address the functional
      significance of biofilm production in the sinus cavities. A further understanding
      of the role of bacterial biofilms may lead to the development of more appropriate
      therapies for the treatment and prevention of chronic sinusitis.

PMID- 17040017
TI  - Surfactant and its role in chronic sinusitis.
AB  - Although numerous studies have focused on the nature and defensive role of
      surfactant in the lower airways, relatively little is known about its role in the
      upper airways. Decreased levels of the main component of surfactant-
      phospholipids--have been implicated in atrophic rhinitis. The lamellar body
      arrangement of phospholipids has now been demonstrated in both normal and
      diseased sinus tissue, resulting in the implication that these structures may
      play a crucial role in mucociliary clearance against inhaled pathogens, as well
      as in the regulation of mucous viscosity. Furthermore, they may be secreted from
      sinonasal ciliated epithelium. Surfactant proteins (SPs) make up a relatively
      smaller proportion of surfactant, but appear to have an important role in innate
      immunity. Altered levels of SPs have been observed in a number of respiratory
      tract diseases. These SPs may prove to play a significant role in chronic
      sinusitis. Demonstrated expression of SP-A and SP-D in diseased and normal sinus
      tissue may mean that these SPs are excreted into the airway-lining fluid of the
      sinuses. Additionally, initial contact and interaction between pathogens and SP-A
      and SP-D may occur relatively early after inhalation and deposition into the
      mucus of the respiratory tract. These findings may lead to potential therapeutic
      options for difficult-to-treat sinus disease in the future.

PMID- 17040018
TI  - Transnasal endoscopy-assisted skull base surgery.
AB  - Skull base surgery (SBS), which originated in the 19th century, became refined in
      the 20th century in parallel with technological advancements and is now in the
      midst of further refinements largely driven by advances in endoscopic sinus
      surgery. With the development of modern SBS, lesions that were once inoperable
      and potentially fatal can now be eradicated successfully by means of endoscopy
      assisted procedures that reduce or completely eliminate intracranial trauma,
      minimize postsurgical morbidity, and make full recovery possible. It is
      absolutely mandatory to have the appropriate instrumentation for endoscopy
      assisted SBS. Among the new technologies available are advanced endoscopes, high
      speed suction irrigation drills, digital video cameras, computed tomography and
      magnetic resonance imaging, and systems for 3-dimensional computer-assisted image
      guided surgical navigation. An experienced endoscopic surgeon working with
      multidisciplinary teams, and using new instrumentation and techniques, can bring
      SBS to new levels of success in the 21st century.

PMID- 17040019
TI  - Evolution of medical management of chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a surprisingly common, poorly defined, and
      notoriously difficult-to-treat disease. It has a complex pathophysiology that
      often, but not always, involves nasal or paranasal sinus infection. Anatomic
      variations that predispose the sinuses to obstruction may play a role, but are
      unusual sole causes of chronic disease. Other possible causative factors include
      allergic or nonallergic inflammation, mucociliary dysfunction, aspirin
      intolerance (Samter's triad), immunodeficiency, and cystic fibrosis. Although a
      majority of patients achieve long-term relief from CRS after successful
      endoscopic sinus surgery, a significant proportion do not, and are likely to
      benefit from sustained postsurgical medical therapy. Medical therapy for CRS may
      include treatment with corticosteroids, antibiotics, antifungal agents,
      antihistamines, leukotriene modifiers, nasal decongestants, mucolytics, and nasal
      irrigations. The selection of appropriate medical therapy is based on endoscopic
      evaluation, sinus cultures, and symptoms. Computed tomography, the imaging
      standard for evaluation of the sinuses, provides information about the extent and
      distribution of mucosal disease beyond what is visible endoscopically. Because it
      fails to provide information on the origin of the mucosal changes, computed
      tomography provides limited information to guide medical therapy.

PMID- 17040020
TI  - Progress in sinonasal imaging.
AB  - Imaging of sinonasal structures has evolved from standard radiographs to the much
      more complicated and informative techniques used today. The plain radiograph was
      useful when the surgical techniques practiced were primarily aimed at the
      maxillary and frontal sinuses. With a better understanding of the mucociliary
      clearance of the nasal cavity and the paranasal sinuses, the surgical technique
      was shifted to the ethmoid sinuses and became more focal, thus needing a better
      understanding and display of the intricate morphology of the nasal cavity and
      paranasal sinuses. Polytomography was a step above plain radiographs and was
      first used in the display of the regional anatomy for the development of
      functional endoscopic sinus surgery. Polytomography was quickly replaced by
      computed tomography, as this imaging technique provides a much more detailed view
      of the sinonasal architecture than does polytomography. Magnetic resonance
      imaging has also shown usefulness in imaging this morphological area, as it
      provides better soft tissue resolution, but it does not allow good visualization
      of bony structures. Newer computer systems with software capable of
      reconstructing the digitized information into a 3-dimensional display further
      enhance our understanding of the regional morphology and afford an improved means
      of correlating the imaging and endoscopic information. Furthermore, stereotactic
      navigation systems allow surgeons the ability to visualize the endoscope
      instrument tip position, as instruments are actively being used during surgery,
      on the computed tomographic and/or magnetic resonance images. There is a
      persistent trend toward reducing the size of the imaging equipment to render it
      more mobile (computed tomography) and adapt it for operating room use.

PMID- 17040021
TI  - Approval of nonprescription sale of Plan B muddies ethical waters.
AB  - The best way to minimize conflicts and confusion over ethical and religious
      issues is to understand provider and patients' rights and have a solid plan in
      place, say ED experts. Make sure you know what your providers are and are not
      willing to do. Staff members who refuse care still are obligated to inform
      patients how they can receive it. Have other physicians or nurses available to
      provide care when such situations arise.

PMID- 17040022
TI  - EDs pool resources to weather flood.
AB  - When disaster strikes your community, creativity can go a long way toward keeping
      your ED up and running, but cooperating with neighboring facilities can double
      your available resources in a hurry. Contact all unscheduled staff members and
      request that they accept additional shifts during the crisis. If nearby
      facilities are shut down, contact their manager to ascertain availability of
      their staff and supplies. Seek additional staffing help from local residency
      programs.

PMID- 17040023
TI  - Hospital planning ahead for bird flu pandemic.
AB  - In preparing your department's response to a pandemic, it's best to plot out
      worst-case scenarios. Once the scenarios have been created, explore all possible
      solutions to equipment and staffing shortages. Since existing capacity will be
      insufficient, identify in advance alternative sites for treating victims. Stay
      abreast of new equipment developments, such as multiple ventilators, that may
      help deal with the added volume of immune compromised patients. Recognize that
      the level of care will be reduced, and adjust your emergency preparedness
      protocols accordingly.

PMID- 17040024
TI  - Satisfaction turnaround requires persistence.
AB  - The key to improving patient satisfaction scores and maintaining those
      improvements lies not only in devising a successful strategy, but in ensuring
      that your staff consistently follow the new procedures. Institute simple changes,
      such as stools in exam rooms, to ensure closer physician-patient contact. Post
      satisfaction scores in the department to make the staff aware of how they are
      performing. Use focus groups and outside experts to generate new ideas for you to
      implement with your staff.

PMID- 17040025
TI  - Will new e-facility help fight ED overcrowding?
AB  - The use of telemedicine to diagnose patients before they come to the ED may
      benefit the operation of your ED, as well as the emergency medicine system in
      general. Potential advantages include the following: By identifying nonemergent
      cases, it can help reduce overcrowding. Since nonemergent patients have the
      longest wait times, it may reduce rates for patients who leave without being seen
      and boost satisfaction. It can help avoid unnecessary transfers to and from the
      ED.

PMID- 17040027
TI  - Patch Adams, MD: healthcare activist.

PMID- 17040026
TI  - Quality- and severity-based payment: will you receive what you earn?
AB  - Pay-for-performance programs that call for healthcare providers to meet external
      quality metrics are being proposed by the Centers for Medicare and Medicaid
      Services and other payers in order to increase the value of dollars spent on
      health care. While linking payment with the quality of health care may be a
      laudable goal, such programs have the potential to test the relationships between
      hospitals and physicians and unfairly penalize hospitals for factors that are
      beyond their control. In the following article, HFMA, with sponsorship from 3M
      Health Information Systems, asks five industry leaders to share their thoughts
      about what pay-for-performance programs may entail, how these programs and
      severity-based payment adjustments may affect their healthcare facilities, and
      strategies healthcare organizations should employ to best prepare.

PMID- 17040028
TI  - Clearing the way for transparency in health care.

PMID- 17040029
TI  - 'What's good today isn't going to be nearly enough tomorrow'.

PMID- 17040030
TI  - Bariatric surgery coverage decision: opportunities and limitations.
AB  - CMS's national coverage decision on bariatric surgery has implications for obese
      patients, insurers, and the physicians and hospitals that treat those patients.
      Other insurers may follow Medicare's lead, causing an increase in patient volume.
      As the number of approved facilities increases, the number of procedures
      performed will grow, bringing in new revenue.

PMID- 17040031
TI  - The myths of benchmarking healthcare IT spending.
AB  - Healthcare organizations should make those IT investments that they believe can
      be managed to achieve an acceptable return. They should make investment decisions
      based on the merits of the IT proposal, not because they have to catch up to
      another industry, such as banking.

PMID- 17040032
TI  - Picking up the pace: accelerating your pricing competency.
AB  - There are at least four things your organization can do to accelerate progress
      toward more defensible, margin-enhancing prices and rates: Choose the right
      starting point. Adopt a pricing formula. Create a pricing toolkit. Align pricing
      roles and responsibilities.

PMID- 17040033
TI  - Developing a defensible pricing strategy. Hospital pricing is a science, not an
      art.
AB  - A more sophisticated approach to establishing hospital pricing strategies should
      include: Reevaluating billing policies and processes to establish payment plans
      and protocols for collection. Establishing a predictable and accurate pricing
      schedule for all services based on variables such as market, cost, and fee
      schedules. Leveraging IT to guide decision making Informing hospital boards of
      the basis for pricing strategies.

PMID- 17040034
TI  - Pricing and paying for proactive care.
AB  - Now that proactive health services are increasingly being paid for by third
      parties, entirely new bases for and kinds of pricing are being practiced. New
      options becoming common include: Pay-for-performance bonuses. Bonuses based on
      achieving disease-specific or risk-specific outcomes. Gainsharing arrangements.

PMID- 17040035
TI  - Capacity management and patient throughput: putting this problem to bed.
AB  - Organizations dealing with capacity issues have several options, including:
      Increasing capacity within current licensed space. Building more beds. Adding
      functional capacity through improving patient throughput. Smoothing demand
      through variability isolation.

PMID- 17040036
TI  - Lean-Six Sigma: tools for rapid cycle cost reduction.
AB  - Organizational costs can be grouped as process cost, cost of quality, and cost of
      poor quality. Providers should train managers in the theory and application of
      Lean-Six Sigma, including the seven categories of waste and how to remove them.
      Healthcare financial executives should work with managers in eliminating waste to
      improve service and reduce costs.

PMID- 17040037
TI  - Beyond budgeting in an IDS: the Park Nicollet experience.
AB  - Beyond budgeting transcends the limitations of traditional budgeting by replacing
      fixed financial targets with targets based on key performance indicators. For
      Park Nicollet Health Services, the decision to implement beyond budgeting
      coincided with a larger move to adopt a Lean approach to management. Park
      Nicollet's process to implement beyond budgeting-from submission of the initial
      proposal through two test runs with process refinements to full implementation
      lasted about one year, from January 2005 to January 2006.

PMID- 17040038
TI  - A formula for success for women (and men!) in leadership.

PMID- 17040039
TI  - Why women's health business development?
AB  - Studies show that women are the primary healthcare decision makers in this
      country; 66 cents of every healthcare dollar is spent on or by women. The
      Department of Health and Human Services will spend $8.3 billion on women's health
      in 2006.

PMID- 17040040
TI  - Sleep deficit: the performance killer. A conversation with Harvard Medical School
      Professor Charles A. Czeisler.
AB  - Companies today glorify the executive who logs 100-hour workweeks, the road
      warrior who lives out of a suitcase in multiple time zones, and the negotiator
      who takes a red-eye to make an 8 A.M. meeting. But to Dr. Charles A. Czeisler,
      the Baldino Professor of Sleep Medicine at Harvard Medical School, this kind of
      corporate behavior is the antithesis of high performance. In fact, he says, it
      endangers employees and puts their companies at risk. In this interview, Czeisler
      describes four neurobiological functions that affect sleep duration and quality
      as well as individual performance. When these functions fall out of alignment
      because of sleep deprivation, people operate at a far lower level of performance
      than they would if they were well rested. Czeisler goes on to observe that
      corporations have all kinds of policies designed to protect employees- rules
      against smoking, sexual harassment, and so on-but they push people to the brink
      of self-destruction by expecting them to work too hard, too long, and with too
      little sleep. The negative effects on cognitive performance, Czeisler says, can
      be similar to those that occur after drinking too much alcohol: "We now know that
      24 hours without sleep or a week of sleeping four or five hours a night induces
      an impairment equivalent to a blood alcohol level of .1%. We would never say,
      'This person is a great worker! He's drunk all the time!' yet we continue to
      celebrate people who sacrifice sleep for work." Czeisler recommends that
      companies institute corporate sleep policies that discourage scheduled work
      beyond 16 consecutive hours as well as working or driving immediately after late
      night or overnight flights. A sidebar to this article summarizes the latest
      developments in sleep research.

PMID- 17040041
TI  - The tools of cooperation and change.
AB  - Employers can choose from lots of tools when they want to encourage employees to
      work together toward a new corporate goal. One of the rarest managerial skills is
      the ability to understand which tools will work in a given situation and which
      will misfire. Cooperation tools fall into four major categories: power,
      management, leadership, and culture. Choosing the right tool, say the authors,
      requires assessing the organization along two critical dimensions: the extent to
      which people agree on what they want and the extent to which they agree on cause
      and effect, or how to get what they want. The authors plot on a matrix where
      various organizations fall along these two dimensions. Employees represented in
      the lower-left quadrant of the model, for example, disagree strongly both about
      what they want and on what actions will produce which results. Those in the upper
      right quadrant agree on both dimensions. Different quadrants call for different
      tools. When employees share little consensus on either dimension, for instance,
      the only methods that will elicit cooperation are "power tools" such as fiat,
      force, and threats. Yugoslavia's Josip Broz Tito wielded such devices
      effectively. So did Jamie Dimon, current CEO of J.P. Morgan Chase, during the
      bank's integration with Bank One. For employees who agree on what they want but
      not on how to get it--think of Microsoft in 1995--leadership tools, such as
      vision statements, are more appropriate. Some leaders are blessed with an
      instinct for choosing the right tools--Continental Airlines' Gordon Bethune,
      General Electric's Jack Welch, and IBM's Lou Gerstner are all examples. Others
      can use this framework to help select the most appropriate tools for their
      circumstances.

PMID- 17040042
TI  - Ideas as art. Interview by Dane Cutu.
AB  - Three years ago, consultants Laurence Prusak and Thomas H. Davenport asked
      prominent management thinkers to name their gurus and reported the results in
      HBR. James G. March appeared on more lists than any other person except Peter
      Drucker. A professor emeritus in management, sociology, political science, and
      education at Stanford University, March has taught courses in subjects as diverse
      as organizational psychology, behavioral economics, leadership, rules for killing
      people, friendship, computer simulation, and statistics. He is perhaps best known
      for his pioneering contributions to organization and management theory. March's
      accomplishments in that field, and in many others, have conferred on him an
      almost unprecedented reputation as a rigorous scholar and a deep source of
      wisdom. As University of Chicago professor John Padgett wrote in the journal
      Contemporary Sociology, "March's influence, unlike that of any of his peers, is
      not limited to any possible subset of the social science disciplines; it is
      pervasive." March approaches thought aesthetically; he cares that ideas have
      "some form of elegance or grace or surprise." His poetic sensibility can be felt
      in the metaphors he has created over the years--the "garbage can theory" of
      organizational choice, for instance, and the "hot-stove effect" in learning. In
      this edited interview with HBR senior editor Diane Coutu, March shares his
      thinking on aesthetics, leadership, the role of folly, and the irrelevance of
      relevance when it comes to the pursuit of ideas. He also comments on the
      fundamental differences between academic and experiential knowledge, underscoring
      the need for both.

PMID- 17040043
TI  - Meeting the challenge of corporate entrepreneurship.
AB  - To be competitive, companies must grow innovative new businesses. Corporate
      entrepreneurship, however, isn't easy. New ventures face innumerable barriers and
      seldom mesh smoothly with well-established systems, processes, and cultures.
      Nonetheless, success requires a balance of old and new organizational traits-and
      unless companies keep those opposing forces in equilibrium, their new businesses
      will flounder. The authors describe the challenges companies face when they
      pursue new businesses, as well as the usual problematic responses to those
      challenges. Such companies, they say, must perform three balancing acts: Develop
      strategy by trial and error, which includes narrowing potential choices, learning
      from small samples, using prototypes to test business models, tracking progress
      through nonfinancial measures, and knowing how and when to pull the plug on a new
      venture. Find the best combination of old and new operational processes by
      staffing new ventures with "mature turks", changing veterans' thinking, knowing
      which capabilities to develop and which to acquire, and having old and new
      businesses share responsibility for operating decisions. Strike the right balance
      of integration and autonomy by assigning both corporate and operating sponsors to
      new ventures, establishing criteria for handoffs to existing divisions, and using
      creative organizational structures. The authors provide a detailed look at IBM's
      Emerging Business Opportunity system, which manages all these balancing acts
      simultaneously.

PMID- 17040044
TI  - Can science be a business? Lessons from biotech.
AB  - In 1976, Genentech, the first biotechnology company, was founded by a young
      venture capitalist and a university professor to exploit recombinant DNA
      technology. Thirty years and more than 300 billion dollars in investments later,
      only a handful of biotech firms have matched Genentech's success or even shown a
      profit. No avalanche of new drugs has hit the market, and the long-awaited
      breakthrough in R&D productivity has yet to materialize. This disappointing
      performance raises a question: Can organizations motivated by the need to make
      profits and please shareholders successfully conduct basic scientific research as
      a core activity? The question has largely been ignored, despite intense debate
      over whether business's invasion of basic science-long the domain of universities
      and nonprofit research institutions- is limiting access to discoveries, thereby
      slowing advances in science. Biotech has not lived up to its promise, says the
      author, because its anatomy, which has worked well in other high-tech sectors,
      can't handle the fundamental challenges facing drug R&D: profound, persistent
      uncertainty and high risks rooted in the limited knowledge of human biology; the
      need for the diverse disciplines involved in drug discovery to work together in
      an integrated fashion; and barriers to learning, including tacit knowledge and
      murky intellectual property rights, which can slow the pace of scientific
      advance. A more suitable anatomy would include increased vertical integration; a
      smaller number of closer, longer collaborations; an emphasis by universities on
      sharing rather than patenting scientific discoveries; more cross-disciplinary
      academic research; and more federal and private funding for translational
      research, which bridges basic and applied science. With such modifications,
      science can be a business.

PMID- 17040045
TI  - What business are you in? Classic advice from Theodore Levitt.
AB  - For all the talk about management as a science, experienced executives know that
      strategic decisions and tactics depend heavily on context. No one understood this
      better than Theodore Levitt (1925-2006). A Harvard Business School professor
      renowned as a founder of modern marketing, he sought above all to use his
      knowledge to serve the needs of businesspeople. In a series of powerfully
      insightful--and delightfully written--essays in Harvard Business Review, he
      provoked readers to reexamine their settled thinking about vital issues so that
      they could better meet the needs of customers. Levitt had the gifts of
      provocation and generalization, offering ideas that startled readers but
      compelled them to think creatively and intelligently about their companies.
      Writing in a period when business was held in far less esteem than it is today,
      he rejected the easy contempt that many intellectuals had for managers and
      consumers. Levitt carried that practical approach to his tenure at Harvard
      Business Review from 1985 to 1989. As one of HBR's most intellectual and most
      populist chief editors, he understood that the magazine's main purpose was to
      serve as a kind of sophisticated translation, clarifying authors' raw-and
      sometimes rough-ideas for impatient, time-pressed readers. This tribute, a look
      into one of business's great minds, offers excerpts from six of Levitt's most
      influential HBR articles: "Marketing Myopia" (July-August 1960) "After the Sale
      Is Over..."(SeptemberOctober1983) "Marketing Success Through Differentiation-of
      Anything" (January-February 1980) "Production-Line Approach to Service"
      (September-October 1972) "The Globalization of Markets" (May-June 1983)
      "Creativity Is Not Enough" (May-June 1963).

PMID- 17040046
TI  - 10 questions for Elizabeth Edwards.

PMID- 17040047
TI  - My right hand.

PMID- 17040048
TI  - What's killing the sea otters.

PMID- 17040049
TI  - Sleep, snoring and the blues.

PMID- 17040050
TI  - The real skinny.

PMID- 17040051
TI  - [Holmium laser enucleation of the prostate: the Kobe City General Hospital
      experience].
AB  - Between October 2004 and August 2005, 43 patients with the mean age of 70.9
      (ranging 57-83) years, who had lower urinary tract symptoms underwent holmium
      laser enucleation of the prostate (HoLEP) at our hospital. The mean operative
      time, change in hemoglobin and resected tissue weight were 193 (83-390) minutes, 
      2.1 (-5.3 -/+ 1.3) g/dl and 40.2 (6.3-90.9) g, respectively. The mean
      postoperative urethral catheter time and postoperative hospital stay were 1.7 and
      5.5 days, respectively. Minor prostatic capsular perforation and bladder mucosal
      injuries in 18 cases without need of additional interventions or treatments.
      Blood transfusion for preoperative anemia was needed in one case.
      Postoperatively, high fever occurred in 6 cases including sepsis in one case,
      while recatheterization was needed in 2 cases because of urination difficulty.
      After discharge, meatal stenosis was found in 7 cases, urethral stenosis in 3
      cases including 2 cases with preoperative urethral stenosis. Scrotal abscess
      developed after acute epididymitis in one case. Transient urinary incontinence
      reported in 12 cases, which requires medication or more than 1 pad per day. HoLEP
      improved international prostate symptom score, quality of life score, peak
      urinary flow rates and postvoiding residual urine volumes immediately and
      significantly. HoLEP is a feasible and effective procedure to relieve lower
      urinary tract symptoms, although technical and instrumental advances are required
      to reduce the operative time and complications.

PMID- 17040052
TI  - [Effect of oral lactosucrose supplementation on human enteric oxalate-degrading
      bacteria].
AB  - A variety of oxalate-degrading bacteria including Oxalobacter formigenes and some
      species of Bifidobacterium are known to colonize the human intestinal tract. Oral
      lactosucrose supplementation promotes the growth of Bifidobacterium in the human
      intestine. Therefore, we investigated the effect of oral lactosucrose
      supplementation on enteric oxalate-degrading bacteria in twelve healthy men (age
      ranging from 25 to 39 years). Lactosucrose was orally administered 10 g daily for
      2 weeks without restriction of dietary intake. The total number of oxalate
      degrading bacteria in feces and the 24-hour urinary excretion of oxalate were
      examined before and after lactosucrose supplementation. The total number of
      oxalate degrading-bacteria was significantly increased by lactosucrose
      supplementation (9.20 +/- 0.44 versus 9.77 +/- 0.46, p<0.05), although there was
      no significant change in the urinary oxalate excretion. The oxalate degrading
      bacteria isolated from feces was biochemically identified as Bifidobacterium
      adolescentis. In conclusion, oral supplementation of 10 g lactosucrose daily for
      2 weeks was effective in multiplying oxalate-degrading bacteria, but not in
      reducing urinary oxalate excretion under free non-restricted dietary intake. In
      addition, it was suggested that various species of Bifidobacterium were related
      to degradation of oxalate in the human intestine.

PMID- 17040053
TI  - [Second-line chemotherapy with gemcitabine and cisplatin for urothelial cancer
      previously treated with or resistant to M-VAC therapy].
AB  - We evaluated the efficacy of gemcitabine-cisplatin (GC) therapy as a second line
      chemotherapy for recurrent urothelial cancer previously treated with or resistant
      to methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) therapy. Four
      patients who had recurrent cancer after adjuvant M-VAC therapy and five patients
      with resistant lesions to M-VAC were treated by GC. Of the nine patients, three
      completely responded to GC and three obtained partial response. These complete
      responders were cancer-free for 34, 32 and 24 months. In one partial responder,
      the metastatic masses have been decreasing in size for 12 months after completion
      of GC therapy. Our findings suggested that GC would be useful as a second line
      chemotherapy for urothelial cancer previously treated with M-VAC.

PMID- 17040054
TI  - [Does early vascular access intervention therapy reduce acute obstruction and
      reconstruction of arterial-venous fistula?].
AB  - Acute vascular access (VA) obstruction is one of the most common complications
      for hemodialysis patients and medical professions. We performed early vascular
      access intervention therapy (VAIVT) to reduce the incidence of acute VA
      obstruction, VAIVT and fistula reconstruction. During a 2-year period, we
      performed 125 procedures of VAIVT in 145 cases in 50 patients who underwent
      arterio-venous fistula angiography. We performed early VAIVT within two weeks
      since we clinically found VA stenosis. The 125 procedures of VAIVT (95 non
      thrombosed cases, 30 thrombosed cases) involved 86 native fistulas (74 non
      thrombosed, 12 thrombosed) and 39 graft fistulas (21 non-thrombosed, 18
      thrombosed). Prevalence of thrombosed cases was significantly higher in graft
      fistula than in native fistula (P<0.001). The primary patency rate in 50 patients
      at 6, 12 and 24 months was 62.1, 46.9 and 41.7%, respectively, while the
      secondary patency rate was 93.7, 90.7 and 86.6%, respectively. The highest
      primary patency rate was found in the non-thrombosed group with native fistula
      and the lowest secondary patency rate was found in the thrombosed group with
      graft fistula. By comparing the results of this study with the events for the
      previous 2 years, the total VAIVT number was almost the same. The number of non
      thrombosed cases increased significantly from 54 to 95, and those of thrombosed
      cases decreased from 68 to 30 (P < 0.001). The number of fistula reconstructions
      significantly decreased from 59 to 22 (P<0.001). Early VAIVT for VA stenosis
      could decrease acute VA obstruction and fistula reconstruction without increasing
      the total number of VAIVT.

PMID- 17040055
TI  - [Solitary fibrous tumor of a kidney: a case report].
AB  - We report a case of solitary fibrous tumor (SFT) arising from a kidney. The
      patient was an 18-year-old female who visited our hospital with the complaint of
      left abdominal pain. Computed tomography revealed a slightly enhanced tumor of
      approximately 3 cm in diameter near the upper calyx of the left kidney. Renal
      cell carcinoma was suspected, and left nephrectomy was performed under
      laparoscopy. Histopathological examination revealed proliferation of CD34
      positive spindle-shaped cells, and a diagnosis of SFT was made. There has been no
      local recurrence or distant metastasis for 15 months after the operation.

PMID- 17040056
TI  - [A case of retroperitoneal schwannoma extracted by a nerve sparing procedure
      under microscopic surgery].
AB  - We report a case in which we extracted retroperitoneal schwannoma by a nerve
      sparing procedure under microscopic surgery. A 63-year-old male was diagnosed
      with left ureter stone and left hydronephrosis. A left retroperitoneal tumor was
      found by the abdominal ultrasound sonography. Abdominal computed tomography and
      magnetic resonance imaging revealed the mass 20 mm in diameter in the
      retroperitoneal cavity. We considered that the tumor arose from the left femoral
      nerve, and removed it under microscopic surgery. There was no malignancy. There
      was neither recurrence nor neuropathy after operation. Since it is rare to find
      the origin nerve of schwannoma before operation, we report our experience.

PMID- 17040057
TI  - [Bladder cancer with skin metastasis: a case report].
AB  - Bladder carcinoma with skin metastasis is extremely rare. We herein report a case
      of a bladder tumor with skin metastasis. A 68-year-old man was referred to our
      hospital with macroscopic hematuria. Cystoscopy revealed a trigone papillary
      tumor. Transurethral resection of bladder tumor (TURBT) was performed and the
      pathological diagnosis was transitional cell carcinoma (TCC), pT1, G3.
      Thereafter, he received several courses of TURBT, intravesical chemotherapy
      (pirarubicin, bacillus Calmette-Guerin and mitomycin C) and intra-arterial
      chemotherapy because of recurrence. Thirteen years later, he underwent total
      cystoprostatectomy with neobladder formation. Histological examination revealed
      muscle-invasive bladder cancer with a staging of T3bNOM0. Two years and three
      months later, multiple firm nodules with eruptions appeared on the skin in
      several regions; they were resected and the histological findings revealed TCC.
      This indicated metastatic spread from the primary bladder TCC. He received only
      supportive treatment during this period due to renal dysfunction. He died four
      months after the manifestation of the skin metastasis due to multiple metastases.

PMID- 17040058
TI  - [A case of transitional cell carcinoma with squamous differentiation which
      developed squamous cell carcinoma in situ in the clinical course].
AB  - In August 2000, a 62-year-old woman presented to another municipal hospital with
      macroscopic Transurethral resection of bladder tumor (TUR-Bt) was performed. The
      pathological hematuria. diagnosis was transitional cell carcinoma (TCC), G2 >
      squamous cell carcinoma (SCC). TUR-Bt repeated in July 2003 indicated recurrence.
      The pathological diagnosis was TCC, G2. She was referred to our hospital in
      August 2003 because she desired bladder preservation. After cystoscopy and random
      biopsy, pathological diagnosis was TCC with squamous differentiation, G1-G2,
      pTis. She received 7 weekly intravesical bacillus Calmette-Guerin (BCG)
      instillations. In April 2004, TUR-Bt was repeated and multiple recurrences were
      found. The pathological diagnosis was TCC with squamous differentiation, G1-G2,
      pTa. She received 10 weekly intravesical Pirarubicin hydrochroride instillations.
      In August cystoscopy and random biopsy were performed for evaluation of the
      intavesical instillation treatment. Pathological diagnosis was atypical squamous
      cells. In November, cystoscopy revealed recurrence of a bladder tumor. After
      admission, a small papillary tumor and multiple flat lesion biopsies demonstrated
      SCC without obvious invasion. The patient underwent cystectomy. There were
      widespread areas of full thickness squamous atypia. Most of the bladder did not
      show appearance of typical TCC, but the final pathological diagnosis was TCC
      because the case developed from TCC and could not be diagnosed as pure SCC. The
      diagnosis of SCC in situ of bladder is difficult, and this may contribute to its
      rarity.

PMID- 17040059
TI  - [Small cell carcinoma of the prostate: a case report].
AB  - A 79-year-old man was admitted to our department with a chief complaint of
      urinary incontinence. The prostate was enlarged (145 cc), although the serum
      level of prostate specific antigen (PSA) was within the normal range (1.09
      ng/ml). Digital rectal examination showed an enlarged, irregular prostate with
      stony hardness. We performed a prostate biopsy and histological examinations
      indicated poorly differentiated adenocarcinoma with a Gleason score of 5+5=10. A
      computed tomographic (CT) scan revealed a prostatic tumor invading the bladder,
      seminal vesicle and rectum. He was diagnosed with a stage T4N1M0 adenocarcinoma
      of the prostate. He was started-on hormonal therapy, but died one month from the
      start of treatment. Histological and immunohistological examinations were
      repeated; suggesting small cell neuroendocrine carcinoma of the prostate.

PMID- 17040060
TI  - Acute myocardial infarction during combined chemotherapy with bleomycin,
      etoposide and cisplatin for testicular cancer.
AB  - We report a case of acute myocardial infarction during combined chemotherapy with
      bleomycin, etoposide and cisplatin for testicular cancer. A 30-year-old smoker
      without any history of ischemic heart disease complained of sudden chest pain on
      the ninth day of his third course of chemotherapy. An electrocardiogram showed ST
      segment elevation in II, III and aVF. Emergency coronary angiography revealed
      total occlusion of the right coronary artery by a thrombus, which was removed by
      coronary atherectomy.

PMID- 17040061
TI  - [A case of myxoid liposarcoma in the right inguinal region: a case report].
AB  - We report a case of myxoid liposarcoma developed in the right inguinal region. A
      45-year-old man visited our hospital with a chief complaint of painless right
      inguinal mass. He was diagnosed with right direct inguinal hernia for the first
      time and received a hernia repair. However, the size of the inguinal mass
      increased gradually after the operation. Then, the tumor was re-evaluated by
      imaging study such as ultrasonography, computed tomography and magnetic resonance
      imaging. A fatty mass 4.0 cm in diameter was demonstrated and the tumor was
      diagnosed as a liposarcoma preoperatively. In addition to the right high
      orchiectomy, surrounding fatty tissue was also removed at the time of the
      operation. Histological examination revealed a myxoid liposarcoma and the
      existence of several daughter regions outside the pseudo-capsule. Right spermatic
      cord and testis were intact. Postoperatively, he received 54 Gy dose of radiation
      therapy to right inguinal region for the prevention of the local recurrence of
      the disease.

PMID- 17040062
TI  - [A case of metastatic tumor of spermatic cord from ascending colon carcinoma].
AB  - A 75-year-old man presented with a left inguinal mass two months after surgery
      for ascending colon cancer. Physical examination revealed a solid mass in the
      left inguinal area. High orchiectomy was performed under the diagnosis of
      spermatic cord tumor. Gross examination of the specimen revealed a 5.0 X 3.2 X
      3.0 cm tumor in the spermatic cord. Pathological examination of the tumor was
      reported as poorly differentiated adenocarcinoma with features similar to those
      of previously resected colon cancer. He developed peritonitis carcinomatosa and
      died 6 months after left orchiectomy. To our knowledge, a metastatic tumor of the
      spermatic cord from colon or rectal cancer is rare. As previously reported, the
      prognosis of this case was also poor.

PMID- 17040064
TI  - [Arterial injury associated with tension-free vaginal tape procedure successfully
      treated by radiological embolization: a case report].
AB  - A 75-year-old woman underwent a tension-free vaginal tape (TVT) procedure for
      urinary stress incontinence. The patient complained of lower abdominal pain, a
      feeling of lower abdominal distension and nausea three hours after the operation.
      In addition, systolic blood pressure decreased gradually to 80 mmHg. Enhanced
      computed tomography revealed a retropubic hematoma sized up to 16 cm X 12 cm X 11
      cm and bleeding from a vessel running through the posterosuperior aspect of the
      pubic bone. Successively, arteriography was performed. The arteriogram also
      confirmed arterial injury, which was successfully treated by selective
      embolization using a gelatin sponge and pushable coils. Postoperative course was
      uneventful requiring neither blood transfusion nor surgical removal of the
      hematoma.

PMID- 17040063
TI  - [A case of leiomyosarcoma of the scrotum: chemotherapy with anti-cancer agents
      was effective for the lung metastasis].
AB  - A 59-year-old male was referred to our hospital with the chief complaint of a
      painless scrotal mass. A 6 X 4.5 X 4 cm elastic hard mass with irregular surface
      was palpable in the right scrotum. We diagnosed a tumor in the right scrotum and
      resected the tumor surgically. Histopathologically, the tumor was liposarcoma of
      the right scrotum. Lung tumors were found 20 months after resection of the
      origin. Systemic chemotherapy with new anti-cancer agents (Paclitaxel and
      Gemcitabine) was performed. The main tumor was reduced to 56% in its diameter
      after 6 courses of chemotherapy. Exclusion of the right middle and lower
      pulmonary lobe was performed. The final pathological diagnosis of the lung tumor
      was metastatic liposarcoma.

PMID- 17040065
TI  - Growth and sporulation of Phytophthora ramorum in vitro in response to
      temperature and light.
AB  - Phytophthora ramorum, recently found in the US, is causing concern for hardwood
      forests and the nursery industry. In an effort to identify some of the
      environmental limitations to growth and sporulation we undertook a laboratory
      study of four US and three European (EU) isolates. On V8 media, isolates grew
      when incubated at 2-28 C and produced chlamydospores at 8-28 C. Sporangia were
      produced at all temperatures tested: 10-30 C for US isolates and 6-26 C for EU
      isolates. Optimal temperatures were 16-26 C for growth, 14-26 C for chlamydospore
      production and 16-22 C for sporangia production. US isolates grew less and
      produced fewer spores when exposed to increasing doses of near-UV radiation (50
      300 microW/cm(2)) and visible radiation (250-1500 microW/cm(2)). EU isolates were
      exposed to 300 microW/cm(2) near-UV only, which significantly reduced growth of
      one of three isolates and had no significant effect on spore production. In our
      studies P. ramorum tolerated a broad range of temperature and light conditions,
      which suggests that it is capable of establishment in a wide geographic area.

PMID- 17040066
TI  - Spatial structure and richness of ectomycorrhizal fungi colonizing bioassay
      seedlings from resistant propagules in a Sierra Nevada forest: comparisons using
      two hosts that exhibit different seedling establishment patterns.
AB  - In this study we analyzed the spatial structure of ectomycorrhizal fungi present
      in the soils as resistant propagules (e.g. spores or sclerotia) in a mixed
      conifer forest in the Sierra Nevada, California. Soils were collected under old
      growth Abies spp. stands across approximately 1 km and bioassayed with seedlings
      of hosts that establish best in stronger light (Pinus jeffreyi) or that are shade
      tolerant (Abies concolor). Ectomycorrhizal fungi colonizing the roots were
      characterized with molecular techniques (ITSRFLP and DNA sequence analysis).
      Wilcoxina, five Rhizopogon species and Cenococcum were the most frequent of 17
      detected species. No spatial structure was detected in the resistant propagule
      community as a whole, but P. jeffreyi seedlings had higher species richness and
      associated with seven Rhizopogon species that were not detected on A. concolor
      seedlings. We drew two conclusions from comparisons between this study and a
      prior study of the ectomycorrhizal community on mature trees in the same forest:
      (i) the resistant propagule community was considerably simpler and more
      homogeneous than the active resident community across the forest and (ii)
      Cenococcum and Wilcoxina species are abundant in both communities.

PMID- 17040067
TI  - Comparison of taxonomic, colony morphotype and PCR-RFLP methods to characterize
      microfungal diversity.
AB  - We compared three methods for estimating fungal species diversity in soil
      samples. A rapid screening method based on gross colony morphological features
      and color reference standards was compared with traditional fungal taxonomic
      methods and PCR-RFLP for estimation of ecological indices of soil microfungal
      community composition. Normalized counts of colony morphotypes on dichloran rose
      bengal medium were used to estimate species richness (S) and evenness (J) and to
      calculate Shannon's diversity (H) and Simpson's (SI) dominance indices. Isolates
      were obtained by dilution plating techniques from litter and soil layer samples
      taken from Douglas-fir forest and clear-cut areas at two locations in the Cascade
      Mountains. The highest correspondence (97%) was observed between taxonomic
      identification and RFLP patterns (32:33). Cladistic analyses of PCR-RFLP patterns
      indicated an 81% correspondence between RFLP patterns:colony morphotypes (33:41).
      A correspondence of 78% was observed between traditional taxonomic
      identification:colony morphotypes (32:41). Statistical analyses of ecological
      indices based on quantitative application of the colony morphotyping method
      indicated significant differences (P < 0.05) in fungal community composition
      between forested and clear-cut areas at the Toad Road site but not at the Falls
      Creek site. Comparisons of ecological indices based on traditional identification
      of taxa by microscopic characterization on defined culture media resulted in
      identical findings of statistical significance. The colony morphotyping approach
      is proposed as a screening method to identify potential effects of land
      management practices, edaphic factors and pollutants on microfungal diversity.

PMID- 17040068
TI  - 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated
      strains of Candida albicans.
AB  - We previously reported the occurrence of chromosome alterations in a Candida
      albicans prototrophic strain 3153A treated with 5-fluoro-orotic acid (5-FOA). In
      this study we investigated the mutagenic properties of 5-FOA with two derivatives
      of C. albicans strain CAF4-2 (ura3/ura3), each containing an ectopic copy of URA3
      gene (ura3/ ura3 URA3) on a different chromosome. As expected, after the
      ura3/ura3 URA3 constructs were applied to 5-FOA containing solid medium, the "pop
      outs" that lost URA3 appeared. However most of the "pop-outs" acquired various
      chromosome alterations. Thus constructs exposed to 5-FOA should be examined for
      chromosome alterations or the use of 5-FOA should be avoided.

PMID- 17040069
TI  - Isolation of cell wall mutants in Aspergillus nidulans by screening for
      hypersensitivity to Calcofluor White.
AB  - As a first step toward identifying novel genes of wall metabolism in filamentous
      fungi, we have screened a collection of Aspergillus nidulans mutants for strains
      exhibiting hypersensitivity toward the chitin binding agent Calcofluor White
      (CFW). This strategy has been used previously to identify cell wall mutants in
      Saccharomyces cerevisiae. We have identified 10 mutants representing eight loci,
      designated calA through calH, for Calcofluor hypersensitivity. All cal mutants
      are impaired for sporulation at 30 C or 42 C or both, and in eight of the 10
      mutations this sporulation defect shows at least partial osmotic remediability.
      All cal mutants show elevated sensitivity to one or more of the following agents:
      Caspofungin, Nikkomycin, Tunicamycin, Congo red and SDS, which are recognized
      wall-compromising agents or have been shown to be inhibitory to wall integrity
      mutants in yeast. Seven of the 10 cal mutants show swelling at elevated
      temperature, which in most cases is osmotically remediable. Spore swelling also
      can be induced at 30 C in all but one of the cal mutants by germination in the
      presence of one or more of the following: Caspofungin, Nikkomycin or Tunicamycin.
      Analysis of wall sugars showed no major changes in mutant strains. We also report
      that the chitin synthase inhibitor Nikkomycin induces excessive spore swelling
      during germination in all tested strains that have wild type cell wall metabolism
      (GR5, A4, A28 and AH12) at 42 C but not at 30 C. This effect mimics that of
      certain temperature-sensitive swollen cell (swo) mutations.

PMID- 17040071
TI  - Three new Lasiodiplodia spp. from the tropics, recognized based on DNA sequence
      comparisons and morphology.
AB  - Botryosphaeria rhodina (anamorph Lasiodiplodia theobromae) is a common endophyte
      and opportunistic pathogen on more than 500 tree species in the tropics and
      subtropics. During routine disease surveys of plantations in Australia and
      Venezuela several isolates differing from L. theobromae were identified and
      subsequently characterized based upon morphology and ITS and EF1-alpha nucleotide
      sequences. These isolates grouped into three strongly supported clades related to
      but different from the known taxa, B. rhodina and L. gonubiensis, These have been
      described here as three new species L. venezuelensis sp. nov., L. crassispora sp.
      nov. and L. rubropurpurea sp. nov. The three could be distinguished easily from
      each other and the two described species of Lasiodiplodia, thus confirming
      phylogenetic separations. Furthermore all five Lasiodiplodia spp. now recognized
      separated from Diplodia spp. and Dothiorella spp. with 100% bootstrap support.

PMID- 17040070
TI  - Phylogenetic relationships of Pythium and Phytophthora species based on ITS rDNA,
      cytochrome oxidase II and beta-tubulin gene sequences.
AB  - Fifty-eight isolates representing 39 Pythium species and 17 isolates representing
      nine Phytophthora species were chosen to investigate intra- and intergeneric
      relationships with sequence analysis of three genomic areas. The internal
      transcribed spacer regions (ITS1 and ITS2), including the 5.8S gene of the
      ribosomal DNA were PCR amplified with the universal primers ITS1 and ITS4. On the
      other hand 563 bp of the cytochrome oxidase II (cox II) gene was amplified with
      the primer pair FM66 and FM58 for Pythium and FM75 and FM78 for Phytophthora. The
      658 bp partial beta-tubulin gene was amplified with the forward primer BT5 and
      reverse primer BT6. Maximum parsimony analysis of the three DNA regions revealed
      four major clades, reflective of sporangial morphology. Clade 1 was composed of
      Pythium isolates that bear filamentous to lobulate sporangia. Clade 2 represents
      Pythium isolates that bear globose to spherical zoosporangia or spherical hyphal
      swellings. Meanwhile Phytophthora isolates were lumped into Clade 3 wherein the
      papillate, semipapillate and nonpapillate species occupied separate subclades.
      Lastly, Clade 4 was composed of Pythium species that bear subglobose sporangia
      resembling the papillate sporangia observed in Phytophthora. Hence a number of
      species (Ph. undulata, P. helicoides, P. ostracodes, P. oedochilum and P. vexans)
      have been proposed to be the elusive intermediate species in the Pythium-to
      Phytophthora evolutionary line.

PMID- 17040073
TI  - Morphology and development of the reticuloperidial ascomata of Auxarthron
      conjugatum.
AB  - Light and electron microscopy showed that the reticuloperidium of thick-walled
      hyphae, characteristic of the mature ascoma of Auxarthron conjugaturn, originated
      from branches that grew from the broad, gyre-like hyphal loops making up the
      ascomatal initials. Within the developing peridium, short, acropetally
      proliferating chains of prototunicate asci each arose from a single crozier and
      matured from base to tip. The walls of young asci were two-layered but evanesced
      as they matured with the outer layer dissolving before the inner one. Distal asci
      in some chains retained the inner wall, detached from adjacent asci by septum
      schizolysis and when transferred to fresh media produced germ tubes and mycelium.
      Ultraviolet epifluorescent staining with a DNA intercalator (Hoechst) indicated
      that these spore-like asci probably contained diploid nuclei. In normal asci,
      ascospores had an inner, electron lucent primary wall and a three-layered
      secondary wall. The deposition pattern of the middle layer of the secondary wall
      created the distinctive array of pits and ridges characteristic of the ascospores
      in this taxon. The production of ascospores, spore-like asci and arthroconidia,
      along with the tendency of ascospores to adhere in a mass, is interpreted as
      contributing to the reproductive flexibility and inoculum potential of A.
      conjugatum. In all respects the ascomata of A. conjugatum differed substantially
      from the morphologically similar taxon, Myxotrichum arcticum. These findings
      underscore the benefit of using DNA-based phylogenies in concert with cytological
      and ultrastructural observations for exploring selective pressures behind
      homoplasious characters and revealing novel structural features.

PMID- 17040072
TI  - Multilocus sequence data reveal extensive phylogenetic species diversity within
      the Neurospora discreta complex.
AB  - Previous observations of morphological, reproductive and genetic variation have
      suggested that Neurospora discreta, as presently circumscribed, might represent a
      diverse complex of multiple species. To investigate this hypothesis we examined
      the phylogenetic relationships among 73 fungal strains traditionally identified
      as N. discreta. Strains were chosen from across the morphological, ecological and
      geographical ranges of the species. Sequence data were obtained from three
      unlinked nuclear loci, and phylogenetic species recognition was applied to the
      dataset using protocols that have been shown to be reliable for identifying
      independent lineages and delineating species of Neurospora. The results
      demonstrate that the present circumscription of N. discreta includes at least
      eight separate phylogenetic species. This research also reveals an abundance of
      previously unrecognized genetic diversity within the genus, characterizes the
      interspecific evolutionary relationships and contributes to a fuller
      understanding of species diversity in Neurospora.

PMID- 17040074
TI  - Gerronema wildpretii sp. nov. (Agaricales, Basidiomycetes) a new species from the
      Canary Islands.
AB  - Gerronema wildpretii, collected in climactic sites of the monteverde forest of
      the Canary Islands is described and illustrated. Its macro- and microscopic
      features delimit this taxon as a new species.

PMID- 17040075
TI  - Vittatispora, a new melanosporaceous genus from Indian soil.
AB  - Vittatispora coorgii gen. sp. nov., isolated from soil in India, is described and
      illustrated. The fungus has morphological characteristics of the genera
      Melanospora, Sphaerodes and Syspastospora. The most striking feature is the
      presence of a thick hyaline ridge along the vertical axis of the lemon-shaped
      ascospores wall. Perithecia also have a long neck composed of adhering hyphae,
      similar to that of Syspatospora. Phylogenetic studies on the 28S rDNA indicate it
      is closely related to Melanospora and Sphaerodes and belongs in the
      Ceratostomataceae. The new genus is based on the distinctive morphology and
      phylogenetic analyses. The fungus grew in culture only conjointly with a sterile
      fungus which a BLAST analysis suggested was close to Tetracladium marchalianum.

PMID- 17040076
TI  - Rediscovery of Alnicola cholea (Cortinariaceae): taxonomic revision and
      description of its mycorrhiza with Polygonum viviparum (Polygonaceae).
AB  - Alnicola cholea, a little-known species so far reported only from the two
      original localities in the French Alps, is redefined here based on revision of
      herbarium materials and studies of recent field collections. A detailed
      morphological and anatomical description of fruit bodies of Alnicola cholea,
      including a discussion on its taxonomic status and distribution data is provided.
      Due to the unique combination of characters of Alnicola cholea within the genus,
      a new monospecific section is introduced for this species: Alnicola sect. Cholea,
      sect. nov. Mycorrhizal symbiosis of A. cholea with an arcticalpine plant
      Polygonum viviparum was observed in the Tatra Mountains (Poland). A description
      of these mycorrhizae is given, providing first detailed data on an identified
      herbaceous plant mycorrhiza.

PMID- 17040077
TI  - Trichomycetes from China and the description of three new Smittium species.
AB  - Trichomycetes were recovered from the guts of aquatic insect larvae collected
      from a stream in the Qinling Mountains in western China. These collections
      included Smittium hecatei, known only from Spain, as well as Smittium simulii and
      Stachylina penetralis, which appear to be more widely distributed. Caudomyces
      japonicus, previously recorded only from Japan, also is reported from crane fly
      larvae (Antocha sp.) from China. We describe three new species, Smittium
      chinliense from a tipulid host, as well as Smittium naiadis and Smittium
      nodifixum, both from chironomid larvae. A probable new species of Gauthieromyces
      was collected in mayfly nymphs and is illustrated but not described here.

PMID- 17040078
TI  - Anamorphic fungi from French Guyana: two undescribed Gliocephalotrichum species
      (Nectriaceae, Hypocreales).
AB  - Morphological and molecular studies of Gliocephalotrichum collections from rain
      forest leaf litter in French Guyana revealed the occurrence of two undescribed
      species, described here as G. bacillisporum and G. longibrachium. Both species
      have a whorl of sterile stipe extensions directly subtending the conidiogenous
      penicilli. Gliocephalotrichum bulbilium also was isolated from leaf litter in
      French Guyana. Two sequences in GenBank, of uncultured ascomycetes from Gabon,
      Africa, cluster in the Gliocephalotrichum clade, suggesting the probable
      existence of additional undescribed taxa from the Central African rainforest.

PMID- 17040079
TI  - Hypocrea crystalligena sp. nov., a common European species with a white-spored
      Trichoderma anamorph.
AB  - The new species Hypocrea crystalligena (Hypocreales, Ascomycota, Fungi) is
      described as a holomorph and characterized based on an integrated phenotypic and
      phylogenetic approach, using teleomorph and anamorph morphologies, culture
      studies and analyses of phylogenetic markers including internal transcribed
      spacer 1 and 2 (ITS1 and 2), two last introns of the translation elongation
      factor 1-alpha encoding gene (tef1), and a portion of the rpb2 gene, encoding the
      second largest RNA polymerase subunit. Stromata of H. crystalligena show
      similarities with those of species from Trichoderma sect. Trichoderma but differ
      in several respects, including color, presence of white crystals on the surface
      and small ascospores. Colonies on CMD appear distinct, form colorless to white
      crystals on isolation, a yellowish to brown pigment and an anamorph with hyaline
      conidia exhibiting verticillium-like to gliocladium-like structural elements.
      ITS1 and 2 sequences exhibit all genus-specific features but also contain several
      unique hallmarks permitting development of a species-diagnostic barcode. Based on
      the analyses of partial rpb2 and tef1 sequences, H. crystalligena constitutes a
      separate evolutionary lineage with H. megalocitrina and H. psychrophila as its
      nearest neighbors. All these species form one phylogenetic clade with the H.
      pulvinata/H. citrina node.

PMID- 17040080
TI  - A strategy for recovering high quality genomic DNA from a large number of
      Phytophthora isolates.
AB  - We present a strategy to recover high molecular weight genomic DNA from large
      numbers of isolates of Phytophthora. Included are steps for generating mycelial
      mass in 24-well reuseable deep well plates, efficient lyophilization and
      disruption of the mycelium and genomic DNA extraction with 96-well glass fiber
      filter plates. The resulting DNA is consistently high molecular weight and is
      suitable for applications that require high quality DNA such as AFLP analysis and
      TILLING. A single operator easily can manage mycelium preparation and/or DNA
      extraction from 384 isolates in a single day and this approach might be useful
      for other fungi or fungi-like organisms that can be grown in liquid media.

PMID- 17040081
TI  - Editors' preface: reflexivity and responsiveness: the expansive orbit of
      knowledge.

PMID- 17040082
TI  - Mindblindness: autism, writing, and the problem of empathy.

PMID- 17040083
TI  - Autism and the contemporary sentimental: fiction and the narrative fascination of
      the present.

PMID- 17040084
TI  - Listening to Chekhov: narrative approaches to depression.

PMID- 17040085
TI  - Enlightening the fibre-woven body: William Blake and eighteenth-century fibre
      medicine.

PMID- 17040086
TI  - Writing against memory and forgetting.

PMID- 17040087
TI  - Trauma, narrative, and two forms of death.

PMID- 17040088
TI  - "Himself he devises too for company": self-making in Samuel Beckett's Company.

PMID- 17040089
TI  - Medical-industrial Discourses: Muriel Rukeyser's "The Book of the Dead".

PMID- 17040090
TI  - A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome)
      in Advanced Soft Tissue Sarcoma.
AB  - Thirty four patients with advanced soft tissue sarcoma not previously treated
      with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty
      three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20
      patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3
      toxicities were rare. Among 32 patients assessable for response, one patient had
      a partial response, giving a response rate of 3.13% (95% confidence interval,
      0.08-16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%)
      had disease progression. The median time to progression for all patients was 42
      days (95% CI, 39-49) and the progression-free rate at 3 months was 12.5%. In
      conclusion, DaunoXome at this dose and schedule is well tolerated in patients
      with advanced soft tissue sarcoma, but is not associated with significant
      activity. Further studies at this dose and schedule cannot be recommended in this
      disease.

PMID- 17040091
TI  - Relative hypocalcaemia and muscle cramps in patients receiving imatinib for
      gastrointestinal stromal tumour.
AB  - Purpose. Imatinib treatment causes muscle cramps in up to 40% of patients, but
      their pathogenesis is unknown. We present a case series illustrating an
      association between imatinib, relative hypocalcaemia, and the development of
      cramps. Patients. The index patient developed muscle spasms and cramps after
      receiving imatinib for gastrointestinal stromal tumour (GIST) for 5 months. The
      adjusted serum calcium had dropped to the lower limit of normal. The low serum
      calcium and muscle cramps improved on stopping imatinib and recurred on
      rechallenge. We reviewed the medical records of 16 further patients. Results. Two
      patients reported muscle cramps (12%). There was a rapid and sustained reduction
      in adjusted serum calcium in the first 6 months from 2.45 +/- 0.11 mmol/L (mean
      +/- SD) to 2.30 +/- 0.08 mmol/L (p = 0.025). Conclusion. Imatinib treatment of
      GIST is associated with reduction in serum calcium which may explain the
      development of neuromuscular symptoms. In patients receiving imatinib, serum
      electrolytes should be monitored and muscle cramps treated by correction of serum
      calcium, or an empirical trial of quinine sulphate.

PMID- 17040092
TI  - The radiation response of sarcomas by histologic subtypes: a review with special
      emphasis given to results achieved with razoxane.
AB  - Purpose. Relatively few results are available in the literature about the
      radiation response of unresectable sarcomas in relation to their histology.
      Therefore, an attempt was made to summarize the present situation. Materials and
      methods. This report is based on a review of the literature and the author's own
      experience. Adult-type soft tissue sarcomas, chondrosarcomas, and chordomas were
      analyzed. Radioresponse was mainly associated with the degree of tumor shrinkage,
      that is, objective responses. Histopathologic responses, that is, the degree of
      necrosis, are only discussed in relation to radiation treatment reports of soft
      tissue sarcomas as a group. Results. Radiation therapy alone leads to major
      responses in about 50% of lipo-, fibro-, leiomyo-, or chondrosarcomas. The
      response rate is less than 50% in malignant fibrous histiocytomas, synovial,
      neurogenic, and other rare soft tissue sarcomas. The response rates may increase
      up to 75% through the addition of radiosensitizers such as halogenated
      pyrimidines or razoxane, or by the use of high-LET irradiation. Angiosarcomas
      become clearly more responsive if biologicals, angiomodulating, and/or tubulin
      affinic substances are given together with radiation therapy. Razoxane is able to
      increase the duration and quality of responses even in difficult-to-treat tumors
      like chondrosarcomas or chordomas. Conclusions. The available data demonstrate
      that the radioresponsiveness of sarcomas is very variable and dependent on
      histology, kind of radiation, and various concomitantly given drugs. The rate of
      complete sustained remissions by radiation therapy alone or in combination with
      drugs is still far from satisfactory although progress has been made through the
      use of sensitizing agents.

PMID- 17040093
TI  - Clinical outcomes of intraoperative radiation therapy for extremity sarcomas.
AB  - Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy,
      presents particular challenges, with significant risks of toxicities. We sought
      to explore the efficacy of intraoperative radiation therapy (IORT) in the
      treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and
      2001, 17 patients received IORT for soft tissue sarcomas of the extremities.
      Indications for IORT included recurrent tumors in a previously radiated field or
      tumors adjacent to critical structures. Results. Gross total resections were
      achieved in all 17 patients. Two patients experienced locoregional relapses, six
      patients recurred at metastatic sites, and one patient died without recurrence.
      Thirty-six month estimates for locoregional control, disease free survival, and
      overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well
      tolerated, with no toxicities referable to IORT. Conclusions. For patients with
      soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides
      excellent local control, with limited acute toxicities.

PMID- 17040094
TI  - Future of toxicology--predictive toxicology: An expanded view of "chemical
      toxicity".
AB  - A chemistry approach to predictive toxicology relies on structure-activity
      relationship (SAR) modeling to predict biological activity from chemical
      structure. Such approaches have proven capabilities when applied to well-defined
      toxicity end points or regions of chemical space. These approaches are less well
      suited, however, to the challenges of global toxicity prediction, i.e., to
      predicting the potential toxicity of structurally diverse chemicals across a wide
      range of end points of regulatory and pharmaceutical concern. New approaches that
      have the potential to significantly improve capabilities in predictive toxicology
      are elaborating the "activity" portion of the SAR paradigm. Recent advances in
      two areas of endeavor are particularly promising. Toxicity data informatics
      relies on standardized data schema, developed for particular areas of
      toxicological study, to facilitate data integration and enable relational
      exploration and mining of data across both historical and new areas of
      toxicological investigation. Bioassay profiling refers to large-scale high
      throughput screening approaches that use chemicals as probes to broadly
      characterize biological response space, extending the concept of chemical
      "properties" to the biological activity domain. The effective capture and
      representation of legacy and new toxicity data into mineable form and the large
      scale generation of new bioassay data in relation to chemical toxicity, both
      employing chemical structure information to inform and integrate diverse
      biological data, are opening exciting new horizons in predictive toxicology.

PMID- 17040095
TI  - Fenton chemistry and iron chelation under physiologically relevant conditions:
      Electrochemistry and kinetics.
AB  - The goal of iron-chelation therapy is to reduce the levels of labile plasma iron,
      and intravenously administered desferrioxamine is the gold standard of
      therapeutic agents. Hydroxypyridinones, e.g., CP20 (3-hydroxy-1,2-dimethylpyridin
      4(1H)-one), are used or are under investigation as orally administered iron
      chelators. We determined electrode potentials of CP20, the related
      hydoxypyridones CP361, CP363, and CP502, and ICL670 (4-[3,5-bis(2-hydroxyphenyl)
      1H-1,2,4-triazol-1-yl]benzoic acid) under physiologically relevant conditions to
      address the question of whether iron in the presence of these chelating agents
      can carry out Fenton chemistry in vivo. We found that iron(III) but not iron(II)
      binds tightly to both CP20 and ICL670 at pH 7 and higher, compared to nearly
      complete binding of 1 microM iron(II) to 10 microM desferrioxamine at pH 7.4 The
      electrode potentials of the hydroxypyridinones shift to more negative values with
      decreasing pK(a) values at lower concentrations of iron(III) (0.02 mM) and ligand
      (0.1 mM). The electrode potential of the iron-CP20 system decreases as a function
      of increasing pH, with a minimum near pH 10.5. We estimate an electrode potential
      for the ascorbyl radical/ascorbate couple under physiological conditions of +105
      mV, which is higher than the electrode potential of the iron(III) complex of CP20
      at all concentrations of iron. The rate of oxidation of iron(II) in the presence
      of CP20 by hydrogen peroxide increases with the concentrations of both ligand and
      peroxide. Although iron(II) is oxidized by hydrogen peroxide, the thus-formed
      Fe(III)(CP20)(3) complex cannot be reduced by ascorbate. Therefore, the tight
      binding of iron(III) by this class of chelators prevents redox cycling.

PMID- 17040096
TI  - Identification of potential genomic biomarkers of hepatotoxicity caused by
      reactive metabolites of N-methylformamide: Application of stable isotope labeled
      compounds in toxicogenomic studies.
AB  - The inability to predict if a metabolically bioactivated compound will cause
      toxicity in later stages of drug development or post-marketing is of serious
      concern. One approach for improving the predictive success of compound toxicity
      has been to compare the gene expression profile in preclinical models dosed with
      novel compounds to a gene expression database generated from compounds with known
      toxicity. While this guilt-by-association approach can be useful, it is often
      difficult to elucidate gene expression changes that may be related to the
      generation of reactive metabolites. In an effort to address this issue, we
      compared the gene expression profiles obtained from animals treated with a soft
      electrophile-producing hepatotoxic compound against corresponding deuterium
      labeled analogues resistant to metabolic processing. Our aim was to identify a
      subset of potential biomarker genes for hepatotoxicity caused by soft
      electrophile-producing compounds. The current study utilized a known hepatotoxic
      compound N-methylformamide (NMF) and its two analogues labeled with deuterium at
      different positions to block metabolic oxidation at the formyl (d(1)) and methyl
      (d(3)) moieties. Groups of mice were dosed with each compound, and their livers
      were harvested at different time intervals. RNA was prepared and analyzed on
      Affymetrix GeneChip arrays. RNA transcripts showing statistically significant
      changes were identified, and selected changes were confirmed using TaqMan RT-PCR.
      Serum clinical chemistry and histopathologic evaluations were performed on
      selected samples as well. The data set generated from the different groups of
      animals enabled us to determine which gene expression changes were attributed to
      the bioactivating pathway. We were able to selectively modulate the metabolism of
      NMF by labeling various positions of the molecule with a stable isotope, allowing
      us to monitor gene changes specifically due to a particular metabolic pathway.
      Two groups of genes were identified, which were associated with the metabolism of
      a certain part of the NMF molecule. The metabolic pathway leading to the
      production of reactive methyl isocyanate resulted in distinct expression patterns
      that correlated with histopathologic findings. There was a clear correlation
      between the expression of certain genes involved in the cell cycle/apoptosis and
      inflammatory pathways and the presence of reactive metabolite. These genes may
      serve as potential genomic biomarkers of hepatotoxicity induced by soft
      electrophile-producing compounds. However, the robustness of these potential
      genomic biomarkers will need to be validated using other hepatotoxicants (both
      soft- and hard-electrophile-producing agents) and compounds known to cause
      idiosyncratic liver toxicity before being adopted into the drug discovery
      screening process.

PMID- 17040097
TI  - Identification and characterization of genes susceptible to transcriptional cross
      talk between the hypoxia and dioxin signaling cascades.
AB  - The aryl hydrocarbon receptor (AHR) and hypoxia inducible factors (HIFs) are
      transcription factors that control the adaptive response to toxicants such as
      dioxins and decreases in available oxygen, respectively. The AHR and HIFs utilize
      the same heterodimeric partner, the aryl hydrocarbon nuclear translocator (ARNT)
      for proper function. This requirement raises the possibility that cross-talk
      exists between these critical signaling systems. Single gene and reporter assays
      have yielded conflicting results regarding the nature of the competition for
      ARNT. Therefore, to determine the extent of cross-talk between the AHR and HIFs,
      a comprehensive analysis was performed using global gene expression analysis. The
      results identified 767 and 430 transcripts that are sensitive to cobalt chloride
      and 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) stimulation, respectively, with
      308 and 176, respectively, exhibiting sensitivity to cross-talk. The overlap
      between these two sets consists of 33 unique transcripts, including the classic
      target genes CYP1A1, carbonic anhydrase IX, and those involved in lipid
      metabolism and coagulation. Computational analysis of the regulatory region of
      these genes identified complex relationships between HIFs, AHR, and their
      respective response elements as well as other DNA motifs, including the SRF, Sp
      1, NF-kB, and AP-2 binding sites. These results suggest that HIF-AHR cross-talk
      is limited to genes with regulatory regions that contain specific motifs and
      architectures.

PMID- 17040098
TI  - Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy")
      and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity
      relationship.
AB  - The toxicological and redox profiles of MDMA and its major metabolites (MDA,
      alpha-methyldopamine, N-methyl-alpha-methyldopamine, 6-hydroxy-alpha
      methyldopamine, 3-methoxy-alpha-methyldopamine) were studied to establish a
      structure-toxicity relationship and determine their individual contribution to
      cell death induction by apoptosis and/or necrosis. The results of the comparative
      toxicity study, using undifferentiated PC12 cells, strongly suggest that the
      metabolites possessing a catecholic group are more toxic to the cells than MDMA
      and metabolites with at least one protected phenolic group. Redox studies reveal
      that an oxidative mechanism seems to play an important role in metabolite
      cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the
      metabolites, particularly N-methyl-alpha-methyldopamine, induce cell death by
      apoptosis, largely accompanied by necrotic features. No significant differences
      were found between MDMA and the metabolites, concerning overall characteristics
      of cell death. These results may be useful to ascertain the contribution of
      metabolism in MDMA neurotoxicity molecular mechanisms.

PMID- 17040099
TI  - Esterification prevents induction of the mitochondrial permeability transition by
      N-acetyl perfluorooctane sulfonamides.
AB  - N-Alkyl perfluorooctane sulfonamides have been widely used as surfactants on
      fabrics and papers, fire retardants, and anticorrosion agents, among many other
      commercial applications. The broad use, global distribution, and environmental
      persistence of these compounds has generated considerable interest regarding
      potentially toxic effects. We have previously reported that
      perfluorooctanesulfonamidoacetate (FOSAA) and N
      ethylperfluorooctanesulfonamidoacetate (N-EtFOSAA) induce the mitochondrial
      permeability transition (MPT) in vitro, resulting in cytochrome c release,
      inhibition of respiration, and generation of reactive oxygen species. By
      synthesizing the corresponding methyl esters of FOSAA and N-EtFOSAA (methyl
      perlfuorinated sulfonamide acetates), we tested the hypothesis that the N-acetate
      moiety of FOSAA and N-EtFOSAA is the functional group responsible for induction
      of the MPT. Swelling of freshly isolated liver mitochondria from Sprague-Dawley
      rats was monitored spectrophotometrically and membrane potential (DeltaPsi) was
      measured using a tetraphenylphosphonium-selective (TPP(+)) electrode. In the
      presence of calcium, 40 microM FOSAA and 7 microM N-EtFOSAA each induced
      mitochondrial swelling and a biphasic depolarization of membrane potential.
      Mitochondrial swelling and the second-phase depolarization were inhibited by
      cyclosporin-A or the catalyst of K(+)/H(+) exchange nigericin, whereas the first
      phase depolarization was not affected by either. In contrast, the methyl esters
      of FOSAA and N-EtFOSAA exhibited no depolarizing or MPT inducing activity.
      Results of this investigation demonstrate that the carboxylic acid moiety of the
      N-acetates is the active functional group, which triggers the MPT by
      perfluorinated sulfonamides.

PMID- 17040100
TI  - Computational prediction of the chromosome-damaging potential of chemicals.
AB  - We report on the generation of computer-based models for the prediction of the
      chromosome-damaging potential of chemicals as assessed in the in vitro chromosome
      aberration (CA) test. On the basis of publicly available CA-test results of more
      than 650 chemical substances, half of which are drug-like compounds, we generated
      two different computational models. The first model was realized using the (Q)SAR
      tool MCASE. Results obtained with this model indicate a limited performance (53%)
      for the assessment of a chromosome-damaging potential (sensitivity), whereas CA
      test negative compounds were correctly predicted with a specificity of 75%. The
      low sensitivity of this model might be explained by the fact that the underlying
      2D-structural descriptors only describe part of the molecular mechanism leading
      to the induction of chromosome aberrations, that is, direct drug-DNA
      interactions. The second model was constructed with a more sophisticated machine
      learning approach and generated a classification model based on 14 molecular
      descriptors, which were obtained after feature selection. The performance of this
      model was superior to the MCASE model, primarily because of an improved
      sensitivity, suggesting that the more complex molecular descriptors in
      combination with statistical learning approaches are better suited to model the
      complex nature of mechanisms leading to a positive effect in the CA-test. An
      analysis of misclassified pharmaceuticals by this model showed that a large part
      of the false-negative predicted compounds were uniquely positive in the CA-test
      but lacked a genotoxic potential in other mutagenicity tests of the regulatory
      testing battery, suggesting that biologically nonsignificant mechanisms could be
      responsible for the observed positive CA-test result. Since such mechanisms are
      not amenable to modeling approaches it is suggested that a positive prediction
      made by the model reflects a biologically significant genotoxic potential. An
      integration of the machine-learning model as a screening tool in early discovery
      phases of drug development is proposed.

PMID- 17040101
TI  - Metabolism of furans in vitro: ipomeanine and 4-ipomeanol.
AB  - Ipomeanine (IPN), 4-ipomeanol (4-IPO), 1-ipomeanol (1-IPO), and 1,4-ipomeadiol
      (DIOL) are toxic 3-substituted furans found in mold-damaged sweet potatoes. IPN
      and 4-IPO are the most toxic, but all produce pulmonary toxicity in cattle and
      rodents, and 4-IPO induces hepatotoxicity in humans. These furans require
      metabolic activation to elicit toxicity, but the limited information obtained
      from previous metabolism studies prompted us to initiate the investigation
      reported here. Our initial studies of 4-IPO metabolism by rat liver microsomes
      demonstrated that the oxidation of 4-IPO to IPN and reduction to DIOL occurred
      and that more IPN was metabolized to a reactive species than 4-IPO or DIOL.
      Incubation of IPN and Gly produced a 2'-pyrrolin-5'-one adduct establishing that
      IPN was metabolized to an enedial. N-Acetylcysteine reacted with the 5'-aldehyde
      of the enedial to give two 2',5'-dihydro-2'-hydroxyfurans stabilized by H bonding
      between the 2'-OH and 3'-keto group. Reaction of the enedial metabolite of IPN
      with one GSH gave several adducts including a pyrrole derived from the 1,2
      addition of GSH to the 5'-aldehyde as well as two tricyclic 2'-pyrrolines derived
      from the 1,4-addition of GSH at the 4'-position. The identities of the pyrrole
      and 2'-pyrroline GSH adducts were confirmed by observation of structurally
      similar adducts from Cys conjugation with the enedial metabolite of IPN. Several
      minor adducts from the conjugation of the enedial metabolite of IPN with two GSH
      were also detected. Mono-GSH and bis-GSH adducts were derived from both the 1,2
      and 1,4-addition of GSH to the enedial metabolite of 4-IPO in rat liver
      microsomal incubations of 4-IPO and GSH. Sequential oxidation of 4-IPO to IPN and
      then to the enedial metabolite followed by GSH conjugation also occurred in the 4
      IPO incubations. The complex structures of the reaction products of the enedial
      with biological nucleophiles may explain why the many attempts to identify 4-IPO
      adducts to protein have not been successful.

PMID- 17040102
TI  - Characterization of the amino acid adducts of the enedial derivative of teucrin
      A.
AB  - The toxicity of germander, a herb used to treat obesity, is attributed to
      cytochrome P450 activation of the furan ring of its major diterpenoid component
      (teucrin A) into a reactive metabolite capable of adducting proteins. 1,4
      Enedials have been proposed to be the reactive products of metabolism, possibly
      arising from a rearrangement of putative epoxide intermediates. We synthesized
      the enedial derivative of teucrin A as well as the enedial derived from a model
      furan, 3-(4-methoxy-benzyloxymethyl)-furan, by dimethyldioxirane oxidation and
      characterized the products of their reactions with amino acids and peptides. The
      reactions of the model enedial, 2-(4-methoxy-benzyloxymethyl)-but-2-enedial, with
      N-acetyl lysine (NAL) afforded regioisomeric N-alkyl-3-pyrrolin-2-ones, differing
      in the substitution on the double bond of the heterocyclic ring. Novel products
      formed in the reactions of the model enedial with N-acetyl cysteine (NAC) and
      both NAC/NAL uncovered the existence of tautomerization between the enedial and a
      hydroxyenal, which was manifest by the loss of 4-methoxybenzylalcohol and the
      incorporation of a second molecule of NAC. The reactions of teucrin A-enedial
      with NAC and NAL afforded analogues of the products observed with the model
      enedial, and the existence of the tautomeric equilibrium resulted in
      epimerization of the proton (H12) adjacent to the former furan ring. This work
      further illuminates the complex chemical behavior of unsaturated dialdehydes as
      an important class of toxic metabolites and lays the foundation for studies of
      the protein targets of teucrin A-enedial.

PMID- 17040103
TI  - Metabolism-dependent mutagenicity of a compound containing a piperazinyl indazole
      motif: Role of a novel p450-mediated metabolic reaction involving a putative
      oxaziridine intermediate.
AB  - Compound 1a (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperazin-1-yl]-propyl}-3,3
      dimethyl-1,3-dihydro-indol-2-one) was mutagenic to Salmonella typhimurium TA98 in
      the presence of rat liver S9 subcellular fraction. The metabolism of 1a in rat
      liver S9 or microsomes demonstrated that it underwent a P450-mediated N
      deindazolation (loss of indazole ring) as a predominant metabolic pathway. To
      investigate a possible link between metabolism and mutagenicity, a structural
      analogue 1b (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperidin-1-yl]-propyl}-3,3
      dimethyl-1,3-dihydro-indol-2-one), the cleaved product 2a (6-chloro-3,3-dimethyl
      5-(3-piperazin-1-yl-propyl)-1,3-dihydro-indol-2-one), and the core motif 3a (3
      piperazinyl indazole) were evaluated in the Ames assay. It was found that 1b was
      not mutagenic to Salmonella typhimurium TA98 in the absence or presence of a
      metabolic activating system. In contrast to 1a, 1b did not undergo the metabolic
      cleavage (loss of indazole ring). Marginal mutagenicity of 2a to TA98 was
      observed with rat liver S9, whereas 3a was shown to be a promutagen. It was
      further demonstrated that 1a inactivated P450 3A, the principle enzyme catalyzing
      the N-deindazolation reaction, in an NADPH-, time-, and concentration-dependent
      manner. The kinetics of inactivation was characterized by a K(I) of 8.1 microM
      and k(inact) of 0.114 min(-1). The differences in mutagenicity between 1a and 1b
      suggest that a chemical bond extending from the 3-position of the indazole to a
      heteroatom (as part of another cyclic ring) is a prerequisite for the toxicity.
      The metabolic process leading to the elimination of the indazole from the rest of
      the molecule apparently plays a key role in causing mutagenicity. It is
      postulated that the N-deindazolation of 1a proceeds via an oxaziridine
      intermediate, the formation of which is indirectly inferred from the presence of
      benzoic acid in microsomal incubations. Benzoic acid is thought to be derived
      from the hydrolysis of 3-indazolone, an unstable product generated from the
      oxaziridine. Evidence suggests that the electrophilic oxaziridine intermediate
      may be responsible for the mutagenicity and inactivation of P450 3A.

PMID- 17040104
TI  - Enhanced sensitivity of Escherichia coli uvrB mutants to mitomycin C points to a
      UV-C distinct repair for DNA adducts.
AB  - Nucleotide excision repair (NER) in Escherichia coli repairs DNA by incising the
      damaged strand on the 3' and 5' sides of the lesion within pyrimidine dimers and
      DNA cross-linking adducts. Cross-linking adducts belong to a class of chemical
      damage to DNA that prevent strand separation, and thus, replication and
      transcription. For this reason, cross-linking agents such as mitomycin C (MC)
      have been used in cancer chemotherapy. The mechanisms involved in MC binding to
      DNA have already been defined; however, the repair of these lesions is not fully
      understood. Our goal was to study the repair of MC DNA lesions in E. coli cells.
      Several bacterial strains with specific mutations were tested for cellular
      inactivation and kinetics of DNA repair through analysis of DNA sedimentation
      profiles in alkaline sucrose gradients. The results obtained show that uvrB
      mutants are extremely sensitive to MC in contrast to the other isogenic uvrA and
      uvrC mutant strains. uvrB mutant strains are unable to repair DNA strand breaks
      produced by MC. Thus, UvrB might play a NER-uncoupled role in the repair of
      lesions induced by MC in vivo, different from its role on the repair of lesions
      produced by UV-C. Also it is suggested that a modified NER system is taking place
      in the repair of MC-adducts.

PMID- 17040105
TI  - Nuclear magnetic resonance studies of the 4R and 4S diastereomers of
      spiroiminodihydantoin 2'-deoxyribonucleosides: absolute configuration and
      conformational features.
AB  - The present study was aimed at gaining further insights into stereochemical and
      conformational features of the 4R and 4S diastereomers of spiroiminodihydantoin
      2'-deoxyribonucleosides that have been shown to be the predominant singlet oxygen
      oxidation products of 2'-deoxyguanosine in aqueous solutions. It may be added
      that spiroiminodihydantoin derivatives are efficiently generated by one-electron
      and singlet oxygen oxidation of the 8-oxo-7,8-dihydroguanine moiety of several
      nucleic acid components including nucleosides, nucleotides, and oligonucleotides.
      The reported structural data on the pair of diastereomeric spiroiminodihydantoin
      2'-deoxyribonucleosides 1 and 2 are mostly inferred from extensive (1)H and (13)C
      NMR analyses including two-dimensional nuclear Overhauser effect measurements
      performed in both D(2)O and dimethyl sulfoxide. This approach that has been shown
      previously to be suitable to assign the stereochemistry of the base moiety of
      oxidized pyrimidine nucleosides was completed by molecular modeling and quantum
      mechanics studies. Thus, application of these two complementary approaches
      together with the consideration of the results of a recent relevant quantum
      mechanic study has allowed the assignment of the absolute stereoconfiguration of
      the C-4 carbon of diastereomers 1 and 2. In addition, information is provided on
      the conformational features of the 2-deoxyribose moiety and the orientation of
      the base around the N-glycosidic bond of both 2'-deoxyribonucleosides 1 and 2.

PMID- 17040107
TI  - Increased DNA damage in ALDH2-deficient alcoholics.
AB  - Drinking alcohol is a risk factor for cancers of the oral cavity, pharynx,
      larynx, and esophagus. Although many studies suggest that acetaldehyde, a major
      metabolite of orally ingested alcohol, plays a crucial role in cancer initiation,
      the link between the aldehyde dehydrogenase-2 (ALDH2) genotype and acetaldehyde
      derived DNA damage has not yet been explored. We have developed a sensitive and
      quantitative method for detecting the acetaldehyde-derived DNA adducts, N(2)
      ethyl-2'-deoxyguanosine (N(2)-Et-dG), alpha-S- and alpha-R-methyl-gamma-hydroxy
      1,N(2)-propano-2'-deoxyguanosine (alpha-S-Me-gamma-OH-PdG and alpha-R-Me-gamma-OH
      PdG), and N(2)-(2,6-dimethyl-1,3-dioxan-4-yl)-deoxyguanosine (N(2)-Dio-dG), by
      using liquid chromatography electrospray tandem mass spectrometry (LC/ESI-MS/MS)
      and stable-isotope internal standards. We determined the DNA adducts in 44 blood
      DNA samples from Japanese alcoholic patients. The levels of three acetaldehyde
      derived DNA adducts, N(2)-Et-dG, alpha-S-Me-gamma-OH-PdG, and alpha-R-Me-gamma-OH
      PdG, were significantly higher in alcoholics with the ALDH2 1/2 2 genotype
      compared to those with the ALDH2 1/2 1 genotype. N(2)-Dio-dG was not detected in
      any of the DNA samples analyzed. These results provide molecular evidence that
      the ALDH2 genotype affects the genotoxic damage caused by acetaldehyde.

PMID- 17040106
TI  - Reductive detoxification of arylhydroxylamine carcinogens by human NADH
      cytochrome b5 reductase and cytochrome b5.
AB  - Heterocyclic and aromatic amine carcinogens are thought to lead to tumor
      initiation via the formation of DNA adducts, and bioactivation to
      arylhydroxylamine metabolites is necessary for reactivity with DNA. Carcinogenic
      arylhydroxylamine metabolites are cleared by a microsomal, NADH-dependent, oxygen
      insensitive reduction pathway in humans, which may be a source of interindividual
      variability in response to aromatic amine carcinogens. The purpose of this study
      was to characterize the identity of this reduction pathway in human liver. On the
      basis of our findings with structurally similar arylhydroxylamine metabolites of
      therapeutic drugs, we hypothesized that the reductive detoxification of
      arylhydroxylamine carcinogens was catalyzed by NADH cytochrome b5 reductase (b5R)
      and cytochrome b5 (cyt b5). We found that reduction of the carcinogenic
      hydroxylamines of the aromatic amine 4-aminobiphenyl (4-ABP; found in cigarette
      smoke) and the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo [4,5-b]
      pyridine (PhIP; found in grilled meats) was indeed catalyzed by a purified system
      containing only human b5R and cyt b5. Specific activities were 56-346-fold higher
      in the purified system as compared to human liver microsomes (HLM), with similar
      Michaelis-Menten constants (K(m) values) in both systems. The stoichiometry for
      b5R and cyt b5 that yielded the highest activity in the purified system was also
      similar to that found in native HLM ( approximately 1:8 to 1:10). Polyclonal
      antisera to either b5R or cyt b5 significantly inhibited N-hydroxy-4
      aminobiphenyl (NHOH-4-ABP) reduction by 95 and 89%, respectively, and
      immunoreactive cyt b5 protein content in individual HLM was significantly
      correlated with individual reduction of both NHOH-4-ABP and N-hydroxy-PhIP (NHOH
      PhIP). Finally, titration of HLM into the purified b5R/cyt b5 system did not
      enhance the efficiency of reduction activity. We conclude that b5R and cyt b5 are
      together solely capable of the reduction of arylhydroxylamine carcinogens, and we
      further hypothesize that this pathway may be a source of individual variability
      with respect to cancer susceptibility following 4-ABP or PhIP exposure.

PMID- 17040108
TI  - Tyrosine-dependent oxidative DNA damage induced by carcinogenic
      tetranitromethane.
AB  - Tetranitromethane (TNM) is used as an oxidizer in rocket propellants and
      explosives and as an additive to increase the cetane number of diesel fuel. TNM
      was reported to induce pulmonary adenocarcinomas and squamous cell carcinomas in
      mice and rats. However, the mechanisms underlying carcinogenesis induced by TNM
      has not yet been clarified. We previously revealed that nitroTyr and nitroTyr
      containing peptides caused Cu(II)-dependent DNA damage in the presence of P450
      reductase, which is considered to yield nitroreduction. Since TNM is a reagent
      for nitration of Tyr in proteins and peptides, we have hypothesized that TNM
      treated Tyr and Tyr-containing peptides induce DNA damage by the modification of
      Tyr. We examined DNA damage induced by TNM-treated amino acids or peptides using
      (32)P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor
      gene and the c-Ha-ras-1 protooncogene. TNM-treated Tyr and Lys-Tyr-Lys induced
      DNA damage including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the
      presence of Cu(II) and NADH. DNA damage was inhibited by catalase and
      bathocuproine, indicating the involvement of H(2)O(2) and Cu(I). The cytosine
      residue of the ACG sequence complementary to codon 273, well-known hotspots of
      the p53 gene, was cleaved with piperidine and Fpg treatments. On the other hand,
      nitroTyr and Lys-nitroTyr-Lys did not induce DNA damage in the presence of Cu(II)
      and NADH. Time-of-flight mass spectrometry confirmed that reactions between Lys
      Tyr-Lys and TNM yielded not only Lys-nitroTyr-Lys but also Lys-nitrosoTyr-Lys.
      Therefore, it is speculated that the nitrosotyrosine residue can induce oxidative
      DNA damage in the presence of Cu(II) and NADH. It is concluded that Tyr-dependent
      DNA damage may play an important role in the carcinogenicity of TNM. TNM is a new
      type of carcinogen that induces DNA damage not by itself but via Tyr
      modification.

PMID- 17040109
TI  - Analysis of crotonaldehyde- and acetaldehyde-derived 1,n(2)-propanodeoxyguanosine
      adducts in DNA from human tissues using liquid chromatography electrospray
      ionization tandem mass spectrometry.
AB  - Crotonaldehyde, a mutagen and carcinogen, reacts with deoxyguanosine (dGuo) in
      DNA to generate a pair of diastereomeric 1,N(2)()-propanodeoxyguanosine adducts
      (Cro-dGuo, 2), which occur in (6S,8S) and (6R,8R) configurations. They can also
      be formed through the consecutive reaction of two acetaldehyde molecules with
      dGuo. Cro-dGuo adducts inhibit DNA synthesis and induce miscoding in human cells.
      Considering their potential role in carcinogenesis, we have developed a sensitive
      and specific liquid chromatography-electrospray ionization-tandem mass
      spectrometry (LC-ESI-MS/MS) method to explore the presence of Cro-dGuo adducts in
      DNA from various human tissues, such as liver, lung, and blood. DNA was isolated
      from human tissues and enzymatically hydrolyzed to deoxyribonucleosides.
      [(15)N(5)]Cro-dGuo was synthesized and used as an internal standard. The Cro-dGuo
      adducts were enriched from the hydrolysate by solid-phase extraction and analyzed
      by LC-ESI-MS/MS using selected reaction monitoring (SRM). This method allows the
      quantitation of the Cro-dGuo adducts at a concentration of 4 fmol/micromol dGuo,
      corresponding to about 1 adduct per 10(9) normal nucleosides starting with 1 mg
      of DNA, with high accuracy and precision. DNA from human liver, lung, and blood
      was analyzed. The Cro-dGuo adducts were detected more frequently in human lung
      DNA than in liver DNA but were not detected in DNA from blood. The results of
      this study provide quantified data on Cro-dGuo adducts in human tissues. The
      higher frequency of Cro-dGuo in lung DNA than in the other tissues investigated
      is potentially important and deserves further study.

PMID- 17040110
TI  - Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from
      adalimumab studies.
AB  - In recent years, there have been major advances in the management of rheumatoid
      arthritis (RA), leading to the development of tumour necrosis factor (TNF)
      antagonists. With these agents, it is possible to arrest joint damage and, by
      treating early in the disease course, to prevent joint damage. It is also now
      thought that early treatment can achieve clinical remission in a substantial
      proportion of patients. With these increased expectations, a change is required
      in the way clinical improvement and drug efficacy is measured. The existing
      standard endpoint commonly used in RA clinical trials, the American College of
      Rheumatology (ACR) 20% response measure, is inadequate for the new goals of
      therapy that should be based on clinical remission and radiographic
      assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown
      to be effective in achieving remission and preventing radiographic progression of
      joint damage in patients with RA and other inflammatory arthropathies, including
      psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in
      patients with early RA, combination treatment with adalimumab plus methotrexate
      (MTX) has been shown to be superior to either treatment alone in inducing
      significant clinical remission while being generally well tolerated. Compared
      with monotherapy, combination therapy resulted in significantly more patients
      (49% vs 25%; p < 0.001) remaining in clinical remission after 2 years.
      Suppression of joint damage assessed by the degree of inhibition of radiographic
      progression was also significantly higher for patients treated with adalimumab
      plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those
      treated with MTX alone. These data support the notion that clinical remission is
      a realistic therapeutic goal in patients with RA.

PMID- 17040111
TI  - Antistaphylococcal vaccines and immunoglobulins: current status and future
      prospects.
AB  - Staphylococci are among the most frequently encountered pathogens in both the
      inpatient and the outpatient setting. Management of infections caused by these
      organisms is complicated by the increasingly common resistance of staphylococcal
      pathogens to commonly used antibacterials. As a consequence, novel approaches to
      prevention and treatment are urgently required. Such approaches include the
      development of vaccines and immunoglobulin preparations targeted at virulence
      factors expressed in vivo by staphylococci. This article reviews the
      biopharmaceutical progress made to date in this field and suggests approaches to
      further progress.

PMID- 17040112
TI  - Short-term therapy for patients with hepatitis C virus genotype 2 or 3 infection.
AB  - In the past 10 years, progress has been made in the management of patients with
      chronic hepatitis C. A sustained virological response (SVR) is achieved in 80-85%
      of patients infected with hepatitis C virus (HCV) genotype 2 or 3 after 24 weeks
      of treatment with peginterferon-alpha and ribavirin. Treatment durations <24
      weeks have been investigated to determine whether shorter-term therapy reduces
      adverse effects and costs compared with longer-term therapy without compromising
      efficacy. Three studies involving only patients with HCV genotype 2 or 3, with
      different baseline patient characteristics have shown that 12-16 weeks of
      treatment can be as effective as 24 weeks of treatment. In all three trials,
      undetectable HCV RNA 4 weeks after the start of treatment was defined as rapid
      virological response (RVR), and only patients with RVR stopped treatment early.
      In the first trial, 75% of patients treated with peginterferon-alpha-2b and
      ribavirin achieved RVR; these rapid responders achieved an SVR rate of 90% after
      14 weeks of treatment. In the second trial, 63% of patients achieved RVR after 4
      weeks of treatment with peginterferon-alpha-2b and ribavirin, and 85% of patients
      with RVR achieved SVR after 12 weeks of treatment. In comparison, 91% of patients
      with RVR treated for 24 weeks had SVR. In the third study, 93% of the total study
      population achieved RVR and were randomly assigned to 16 or 24 weeks of treatment
      with peginterferon-alpha-2a and ribavirin. Among patients with RVR, 85% in the
      group treated for 16 weeks and 80% in the group treated for 24 weeks achieved
      SVR. Among patients with HCV genotype 2 or 3, achieving an RVR to interferon
      based treatment is common and a criterion to reduce the duration of treatment. In
      patients with genotype 2 and RVR, 12 weeks of therapy with peginterferon-alpha
      and ribavirin is recommended. For patients with genotype 3, a univocal
      recommendation on treatment duration cannot be made. However, ongoing trials will
      probably clarify this aspect.

PMID- 17040113
TI  - Combination therapy in epilepsy: when and what to use.
AB  - After being regarded as a last resort for over two decades, the role of
      combination therapy as a treatment strategy for epilepsy is undergoing re
      evaluation. This is a result of the growing appreciation that all seizures cannot
      be controlled by monotherapy in a substantial proportion of patients, and of the
      development of a range of modern antiepileptic drugs (AEDs), some of which are
      better tolerated and less prone to complex pharmacokinetic drug interactions than
      their older counterparts.Robust evidence to guide clinicians on when and how to
      combine AEDs is lacking, and current practice recommendations are largely
      empirical. Monotherapy should remain the treatment of choice for newly diagnosed
      epilepsy. A combination of two AEDs can be considered after failure, resulting
      from lack of efficacy, of one or two different monotherapy regimens. A few
      patients will become seizure-free with a combination of three AEDs, but treatment
      with a combination of four or more is unlikely to be successful. There is some
      evidence to support a pharmacomechanistic approach to AED combination. Care
      should be taken to avoid excessive drug load, which is associated with increased
      toxicity. Bigger and better randomised, controlled studies are needed to
      determine the optimal time and way to combine AEDs.

PMID- 17040115
TI  - Corticosteroid-free strategies in liver transplantation.
AB  - Corticosteroid avoidance is feasible and may be desirable in liver
      transplantation. Approximately 50% of liver transplant recipients who use
      calcineurin inhibitors and azathioprine do not need corticosteroids. The
      availability of newer agents, such as mycophenolate mofetil and antibody therapy,
      has increased the percentage of patients who do not need to use corticosteroids
      to about 75%. The feasibility of corticosteroid-free immunosuppression has been
      established by controlled trials demonstrating non-inferiority with respect to
      patterns of rejection as well as patient and graft survival. However, the
      evidence available to date does not unequivocally establish the benefits of
      corticosteroid-free immunosuppression, although some advantage has been
      established relating to post-transplant diabetes mellitus, cytomegalovirus
      infection and growth patterns in children. The effect of corticosteroid-free
      immunosuppression in hepatitis C liver transplant recipients is yet to be
      resolved.

PMID- 17040114
TI  - Natural course, therapeutic options and economic evaluation of therapies for
      chronic hepatitis B.
AB  - Chronic hepatitis B virus infection afflicts 400 million people worldwide and
      untreated will progress to cirrhosis in 15-40% of individuals, with an associated
      increased risk for the development of hepatocellular carcinoma. The 'inactive
      carrier state' carries a benign prognosis with a very low risk of cirrhosis or
      hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive
      chronic hepatitis state is an active disease state with increased risk for
      progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant
      variety of chronic hepatitis B has been associated with a higher incidence of
      cirrhosis at initial presentation and more frequent progression to hepatocellular
      carcinoma compared with the wild-type hepatitis B. Five medications are currently
      approved by the US FDA for the treatment of chronic hepatitis B: interferon
      alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a.
      Interferon-alpha therapy has been shown to increase the rate of HBeAg and
      hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but
      has significant adverse effects and is ineffective against the HBeAg-negative
      mutant. Lamivudine is a safely used, orally administered drug with good efficacy,
      but is associated with the development of a lamivudine-resistant (Lam-R) mutant
      in a large proportion of patients after long-term therapy. High relapse rates
      after lamivudine therapy make this medication less effective in the HBeAg
      negative mutant also. Adefovir dipivoxil is a safely used, orally administered
      drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is
      effective against the wild-type and HBeAg-negative hepatitis B and has a very low
      incidence of resistance development. Entecavir is a highly potent and selective
      new oral drug against hepatitis B. It has demonstrated no resistance development
      in treatment-naive patients, but a low incidence of resistance in patients
      infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once
      weekly and has improved efficacy compared with standard interferon-alpha and
      lamivudine. However, it has a similar adverse-effect profile to standard
      interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in
      treating chronic hepatitis B patients compared with no therapy. However, results
      have been conflicting, with earlier studies showing a cost advantage of
      lamivudine over interferon-alpha and a more recent, comprehensive study favouring
      interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil
      'salvage' after lamivudine resistance development in HBeAg-positive patients.

PMID- 17040116
TI  - Pioglitazone/metformin.
AB  - A fixed-dose pioglitazone/metformin tablet is approved in the US and the EU for
      the treatment of adult patients with type 2 diabetes mellitus who currently have
      inadequate glycaemic control with metformin monotherapy. In the US, the
      combination tablet is also approved for the treatment of adult patients with type
      2 diabetes who currently have inadequate glycaemic control with pioglitazone
      monotherapy and for those already receiving a combination of pioglitazone and
      metformin. Bioequivalence, based on absorption and bioavailability parameters,
      has been established between the fixed-dose tablets and equivalent doses of
      pioglitazone and metformin coadministered as separate agents. Combination therapy
      with pioglitazone plus metformin was significantly more effective at improving
      both glycaemic and lipid control than metformin plus placebo in patients with
      type 2 diabetes in a 16-week, well designed trial. Pioglitazone plus metformin
      demonstrated similar antihyperglycaemic efficacy to that of rosiglitazone plus
      metformin in a well designed 12-month trial; however, pioglitazone plus metformin
      was the superior combination in terms of lipid control. In several comparative
      trials of 1-3.5 years' duration, pioglitazone plus metformin was at least as
      effective as combination therapy with a sulphonylurea plus metformin in terms of
      antihyperglycaemic efficacy, but provided superior lipidaemic control with regard
      to levels of triglyceride and high-density lipoprotein-cholesterol. Pioglitazone
      plus metformin was generally well tolerated in patients with type 2 diabetes,
      with adverse events common to metformin monotherapy observed at a similar
      incidence to that with metformin plus placebo.

PMID- 17040120
TI  - Valsartan/hydrochlorothiazide: a review of its use in the management of
      hypertension.
AB  - Valsartan/hydrochlorothiazide is a fixed-dose (valsartan 80, 160 or 320mg plus
      hydrochlorothiazide 12.5 or 25mg) angiotensin II receptor blocker/diuretic drug
      combination indicated for the treatment of patients with essential hypertension
      not adequately controlled by monotherapy.There is ample evidence that
      valsartan/hydrochlorothiazide is an effective fixed-dose combination
      antihypertensive agent. However, efficacy and tolerability data pertaining to the
      320mg dose of valsartan in the combination are currently relatively few. There is
      also some evidence of potential benefits associated with the relatively
      favourable tolerability profile of the combination, the low occurrence of new
      onset diabetes mellitus versus amlodipine and the valsartan-associated
      improvements in cardiac and endothelial function.

PMID- 17040121
TI  - Large-scale turnover of functional transcription factor binding sites in
      Drosophila.
AB  - The gain and loss of functional transcription factor binding sites has been
      proposed as a major source of evolutionary change in cis-regulatory DNA and gene
      expression. We have developed an evolutionary model to study binding-site
      turnover that uses multiple sequence alignments to assess the evolutionary
      constraint on individual binding sites, and to map gain and loss events along a
      phylogenetic tree. We apply this model to study the evolutionary dynamics of
      binding sites of the Drosophila melanogaster transcription factor Zeste, using
      genome-wide in vivo (ChIP-chip) binding data to identify functional Zeste binding
      sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and
      D. yakuba to study their evolution. We estimate that more than 5% of functional
      Zeste binding sites in D. melanogaster were gained along the D. melanogaster
      lineage or lost along one of the other lineages. We find that Zeste-bound regions
      have a reduced rate of binding-site loss and an increased rate of binding-site
      gain relative to flanking sequences. Finally, we show that binding-site gains and
      losses are asymmetrically distributed with respect to D. melanogaster, consistent
      with lineage-specific acquisition and loss of Zeste-responsive regulatory
      elements.

PMID- 17040122
TI  - Viral and latent reservoir persistence in HIV-1-infected patients on therapy.
AB  - Despite many years of potent antiretroviral therapy, latently infected cells and
      low levels of plasma virus have been found to persist in HIV-infected patients.
      The factors influencing this persistence and their relative contributions have
      not been fully elucidated and remain controversial. Here, we address these issues
      by developing and employing a simple, but mechanistic viral dynamics model. The
      model has two novel features. First, it assumes that latently infected T cells
      can undergo bystander proliferation without transitioning into active viral
      production. Second, it assumes that the rate of latent cell activation decreases
      with time on antiretroviral therapy due to the activation and subsequent loss of
      latently infected cells specific for common antigens, leaving behind cells that
      are successively less frequently activated. Using the model, we examined the
      quantitative contributions of T cell bystander proliferation, latent cell
      activation, and ongoing viral replication to the stability of the latent
      reservoir and persisting low-level viremia. Not surprisingly, proliferation of
      latently infected cells helped maintain the latent reservoir in spite of loss of
      latent infected cells through activation and death, and affected viral dynamics
      to an extent that depended on the magnitude of latent cell activation. In the
      limit of zero latent cell activation, the latent cell pool and viral load became
      uncoupled. However, as the activation rate increased, the plasma viral load could
      be maintained without depleting the latent reservoir, even in the absence of
      viral replication. The influence of ongoing viral replication on the latent
      reservoir remained insignificant for drug efficacies above the "critical
      efficacy" irrespective of the activation rate. However, for lower drug efficacies
      viral replication enabled the stable maintenance of both the latent reservoir and
      the virus. Our model and analysis methods provide a quantitative and qualitative
      framework for probing how different viral and host factors contribute to the
      dynamics of the latent reservoir and the virus, offering new insights into the
      principal determinants of their persistence.

PMID- 17040123
TI  - Quantitative analyses of circadian gene expression in mammalian cell cultures.
AB  - The central circadian pacemaker is located in the hypothalamus of mammals, but
      essentially the same oscillating system operates in peripheral tissues and even
      in immortalized cell lines. Using luciferase reporters that allow automated
      monitoring of circadian gene expression in mammalian fibroblasts, we report the
      collection and analysis of precise rhythmic data from these cells. We use these
      methods to analyze signaling pathways of peripheral tissues by studying the
      responses of Rat-1 fibroblasts to ten different compounds. To quantify these
      rhythms, which show significant variation and large non-stationarities (damping
      and baseline drifting), we developed a new fast Fourier transform-nonlinear least
      squares analysis procedure that specifically optimizes the quantification of
      amplitude for circadian rhythm data. This enhanced analysis method successfully
      distinguishes among the ten signaling compounds for their rhythm-inducing
      properties. We pursued detailed analyses of the responses to two of these
      compounds that induced the highest amplitude rhythms in fibroblasts, forskolin
      (an activator of adenylyl cyclase), and dexamethasone (an agonist of
      glucocorticoid receptors). Our quantitative analyses clearly indicate that the
      synchronization mechanisms by the cAMP and glucocorticoid pathways are different,
      implying that actions of different genes stimulated by these pathways lead to
      distinctive programs of circadian synchronization.

PMID- 17040124
TI  - The role of compensatory mutations in the emergence of drug resistance.
AB  - Pathogens that evolve resistance to drugs usually have reduced fitness. However,
      mutations that largely compensate for this reduction in fitness often arise. We
      investigate how these compensatory mutations affect population-wide resistance
      emergence as a function of drug treatment. Using a model of gonorrhea
      transmission dynamics, we obtain generally applicable, qualitative results that
      show how compensatory mutations lead to more likely and faster resistance
      emergence. We further show that resistance emergence depends on the level of drug
      use in a strongly nonlinear fashion. We also discuss what data need to be
      obtained to allow future quantitative predictions of resistance emergence.

PMID- 17040125
TI  - Phylogenetic relationships of the Wolbachia of nematodes and arthropods.
AB  - Wolbachia are well known as bacterial symbionts of arthropods, where they are
      reproductive parasites, but have also been described from nematode hosts, where
      the symbiotic interaction has features of mutualism. The majority of arthropod
      Wolbachia belong to clades A and B, while nematode Wolbachia mostly belong to
      clades C and D, but these relationships have been based on analysis of a small
      number of genes. To investigate the evolution and relationships of Wolbachia
      symbionts we have sequenced over 70 kb of the genome of wOvo, a Wolbachia from
      the human-parasitic nematode Onchocerca volvulus, and compared the genes
      identified to orthologues in other sequenced Wolbachia genomes. In comparisons of
      conserved local synteny, we find that wBm, from the nematode Brugia malayi, and
      wMel, from Drosophila melanogaster, are more similar to each other than either is
      to wOvo. Phylogenetic analysis of the protein-coding and ribosomal RNA genes on
      the sequenced fragments supports reciprocal monophyly of nematode and arthropod
      Wolbachia. The nematode Wolbachia did not arise from within the A clade of
      arthropod Wolbachia, and the root of the Wolbachia clade lies between the
      nematode and arthropod symbionts. Using the wOvo sequence, we identified a
      lateral transfer event whereby segments of the Wolbachia genome were inserted
      into the Onchocerca nuclear genome. This event predated the separation of the
      human parasite O. volvulus from its cattle-parasitic sister species, O. ochengi.
      The long association between filarial nematodes and Wolbachia symbionts may
      permit more frequent genetic exchange between their genomes.

PMID- 17040126
TI  - COPI activity coupled with fatty acid biosynthesis is required for viral
      replication.
AB  - During infection by diverse viral families, RNA replication occurs on the surface
      of virally induced cytoplasmic membranes of cellular origin. How this process is
      regulated, and which cellular factors are required, has been unclear. Moreover,
      the host-pathogen interactions that facilitate the formation of this new
      compartment might represent critical determinants of viral pathogenesis, and
      their elucidation may lead to novel insights into the coordination of vesicular
      trafficking events during infection. Here we show that in Drosophila cells,
      Drosophila C virus remodels the Golgi apparatus and forms a novel vesicular
      compartment, on the surface of which viral RNA replication takes place. Using
      genome-wide RNA interference screening, we found that this step in the viral
      lifecycle requires at least two host encoded pathways: the coat protein complex I
      (COPI) coatamer and fatty acid biosynthesis. Our results integrate, clarify, and
      extend numerous observations concerning the cell biology of viral replication,
      allowing us to conclude that the coupling of new cellular membrane formation with
      the budding of these vesicles from the Golgi apparatus allows for the regulated
      generation of this new virogenic organelle, which is essential for viral
      replication. Additionally, because these pathways are also limiting in flies and
      in human cells infected with the related RNA virus poliovirus, they may represent
      novel targets for antiviral therapies.

PMID- 17040127
TI  - Terminal reassortment drives the quantum evolution of type III effectors in
      bacterial pathogens.
AB  - Many bacterial pathogens employ a type III secretion system to deliver type III
      secreted effectors (T3SEs) into host cells, where they interact directly with
      host substrates to modulate defense pathways and promote disease. This
      interaction creates intense selective pressures on these secreted effectors,
      necessitating rapid evolution to overcome host surveillance systems and defenses.
      Using computational and evolutionary approaches, we have identified numerous
      mosaic and truncated T3SEs among animal and plant pathogens. We propose that
      these secreted virulence genes have evolved through a shuffling process we have
      called "terminal reassortment." In terminal reassortment, existing T3SE termini
      are mobilized within the genome, creating random genetic fusions that result in
      chimeric genes. Up to 32% of T3SE families in species with relatively large and
      well-characterized T3SE repertoires show evidence of terminal reassortment, as
      compared to only 7% of non-T3SE families. Terminal reassortment may permit the
      near instantaneous evolution of new T3SEs and appears responsible for major
      modifications to effector activity and function. Because this process plays a
      more significant role in the evolution of T3SEs than non-effectors, it provides
      insight into the evolutionary origins of T3SEs and may also help explain the
      rapid emergence of new infectious agents.

PMID- 17040128
TI  - Two Plasmodium rhomboid proteases preferentially cleave different adhesins
      implicated in all invasive stages of malaria.
AB  - Invasion of host cells by the malaria pathogen Plasmodium relies on parasite
      transmembrane adhesins that engage host-cell receptors. Adhesins must be released
      by cleavage before the parasite can enter the cell, but the processing enzymes
      have remained elusive. Recent work indicates that the Toxoplasma rhomboid
      intramembrane protease TgROM5 catalyzes this essential cleavage. However,
      Plasmodium does not encode a direct TgROM5 homolog. We examined processing of the
      14 Plasmodium falciparum adhesins currently thought to be involved in invasion by
      both model and Plasmodium rhomboid proteases in a heterologous assay. While most
      adhesins contain aromatic transmembrane residues and could not be cleaved by
      nonparasite rhomboid proteins, including Drosophila Rhomboid-1, Plasmodium
      falciparum rhomboid protein (PfROM)4 (PFE0340c) was able to process these
      adhesins efficiently and displayed novel substrate specificity. Conversely,
      PfROM1 (PF11_0150) shared specificity with rhomboid proteases from other
      organisms and was the only PfROM able to cleave apical membrane antigen 1 (AMA1).
      PfROM 1 and/or 4 was thus able to cleave diverse adhesins including TRAP, CTRP,
      MTRAP, PFF0800c, EBA-175, BAEBL, JESEBL, MAEBL, AMA1, Rh1, Rh2a, Rh2b, and Rh4,
      but not PTRAMP, and cleavage relied on the adhesin transmembrane domains.
      Swapping transmembrane regions between BAEBL and AMA1 switched the relative
      preferences of PfROMs 1 and 4 for these two substrates. Our analysis indicates
      that PfROMs 1 and 4 function with different substrate specificities that together
      constitute the specificity of TgROM5 to cleave diverse adhesins. This is the
      first enzymatic analysis of Plasmodium rhomboid proteases and suggests an
      involvement of PfROMs in all invasive stages of the malaria lifecycle, in both
      the vertebrate host and the mosquito vector.

PMID- 17040130
TI  - Cell size checkpoint control by the retinoblastoma tumor suppressor pathway.
AB  - Size control is essential for all proliferating cells, and is thought to be
      regulated by checkpoints that couple cell size to cell cycle progression. The
      aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB)
      tumor suppressor pathway are consistent with a role in size checkpoint control,
      but indirect effects on size caused by altered cell cycle kinetics are difficult
      to rule out. The multiple fission cell cycle of the unicellular alga
      Chlamydomonas reinhardtii uncouples growth from division, allowing direct
      assessment of the relationship between size phenotypes and checkpoint function.
      Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous
      cell divisions and small cells, suggesting a role for MAT3 in size control. We
      identified suppressors of an mat3 null allele that had recessive mutations in DP1
      or dominant mutations in E2F1, loci encoding homologs of a heterodimeric
      transcription factor that is targeted by RB-related proteins. Significantly, we
      determined that the dp1 and e2f1 phenotypes were caused by defects in size
      checkpoint control and were not due to a lengthened cell cycle. Despite their
      cell division defects, mat3, dp1, and e2f1 mutants showed almost no changes in
      periodic transcription of genes induced during S phase and mitosis, many of which
      are conserved targets of the RB pathway. Conversely, we found that regulation of
      cell size was unaffected when S phase and mitotic transcription were inhibited.
      Our data provide direct evidence that the RB pathway mediates cell size
      checkpoint control and suggest that such control is not directly coupled to the
      magnitude of periodic cell cycle transcription.

PMID- 17040132
TI  - Functionality of intergenic transcription: an evolutionary comparison.
AB  - Although a large proportion of human transcription occurs outside the boundaries
      of known genes, the functional significance of this transcription remains
      unknown. We have compared the expression patterns of known genes as well as
      intergenic transcripts within the ENCODE regions between humans and chimpanzees
      in brain, heart, testis, and lymphoblastoid cell lines. We find that intergenic
      transcripts show patterns of tissue-specific conservation of their expression,
      which are comparable to exonic transcripts of known genes. This suggests that
      intergenic transcripts are subject to functional constraints that restrict their
      rate of evolutionary change as well as putative positive selection to an extent
      comparable to that of classical protein-coding genes. In brain and testis, we
      find that part of this intergenic transcription is caused by widespread use of
      alternative promoters. Further, we find that about half of the expression
      differences between humans and chimpanzees are due to intergenic transcripts.

PMID- 17040135
TI  - AAHPM College of Palliative Care: mentorship and career development.

PMID- 17040131
TI  - Forces shaping the fastest evolving regions in the human genome.
AB  - Comparative genomics allow us to search the human genome for segments that were
      extensively changed in the last approximately 5 million years since divergence
      from our common ancestor with chimpanzee, but are highly conserved in other
      species and thus are likely to be functional. We found 202 genomic elements that
      are highly conserved in vertebrates but show evidence of significantly
      accelerated substitution rates in human. These are mostly in non-coding DNA,
      often near genes associated with transcription and DNA binding. Resequencing
      confirmed that the five most accelerated elements are dramatically changed in
      human but not in other primates, with seven times more substitutions in human
      than in chimp. The accelerated elements, and in particular the top five, show a
      strong bias for adenine and thymine to guanine and cytosine nucleotide changes
      and are disproportionately located in high recombination and high guanine and
      cytosine content environments near telomeres, suggesting either biased gene
      conversion or isochore selection. In addition, there is some evidence of
      directional selection in the regions containing the two most accelerated regions.
      A combination of evolutionary forces has contributed to accelerated evolution of
      the fastest evolving elements in the human genome.

PMID- 17040129
TI  - Inferring the demographic history and rate of adaptive substitution in
      Drosophila.
AB  - An important goal of population genetics is to determine the forces that have
      shaped the pattern of genetic variation in natural populations. We developed a
      maximum likelihood method that allows us to infer demographic changes and detect
      recent positive selection (selective sweeps) in populations of varying size from
      DNA polymorphism data. Applying this approach to single nucleotide polymorphism
      data at more than 250 noncoding loci on the X chromosome of Drosophila
      melanogaster from an (ancestral) African population and a (derived) European, we
      found that the African population expanded about 60,000 y ago and that the
      European population split off from the African lineage about 15,800 y ago,
      thereby suffering a severe population size bottleneck. We estimated that about
      160 beneficial mutations (with selection coefficients s between 0.05% and 0.5%)
      were fixed in the euchromatic portion of the X in the African population since
      population size expansion, and about 60 mutations (with s around 0.5%) in the
      diverging European lineage.

PMID- 17040136
TI  - Iraq of the palliative care movement.

PMID- 17040139
TI  - Preventing burnout.

PMID- 17040140
TI  - Applying the concepts from Maslow in a large U.S. hospice program.

PMID- 17040141
TI  - A central role for palliative care in an influenza pandemic.

PMID- 17040142
TI  - Palliative care services in Pennsylvania nursing homes.
AB  - BACKGROUND: Palliative care is an interdisciplinary model that focuses on the
      comprehensive management of physical, psychological, social, and spiritual needs
      of individuals with lifelimiting illness. Although palliative care is
      increasingly common in acute care settings, regulatory, financial, and
      educational barriers often bar nursing home residents from access to palliative
      care services. OBJECTIVE: The purpose of the Palliative Care Services in
      Pennsylvania Nursing Homes Survey was to describe existing palliative care
      services within nursing homes in Pennsylvania, and to classify these services by
      level of care delivery. METHODS: Ninety-one nursing home administrators
      throughout the state of Pennsylvania participated in the mailed survey. Multiple
      logistic regression analysis was used to investigate the association between
      various organizational characteristics and provision of palliative care services.
      RESULTS: Results reveal that urban facilities were more likely to provide
      palliative care services than rural facilities. Urban facilities cited the need
      for bereavement training most frequently, whereas rural clinical cited the need
      for training in pain management. Larger facility size was associated with an
      increased likelihood of pain management practices, even after adjusting for
      regional differences. CONCLUSIONS: These pilot findings are consistent with and
      extend previous findings suggesting that palliative care practice in nursing
      homes is strongly influenced by nonclinical factors and invites further
      investigation.

PMID- 17040143
TI  - Errors in symptom intensity self-assessment by patients receiving outpatient
      palliative care.
AB  - BACKGROUND: Patient-based symptom scores are the standard method for assessment
      in palliative care. There has been limited research on the frequency of errors
      upon using this approach. The Edmonton Symptom Assessment Scale (ESAS) is a
      reliable and valid assessment tool routinely used for symptom intensity
      assessment in our cancer center. OBJECTIVE: To determine if patients were scoring
      the symptoms on the ESAS in the way it was supposed to be scored. SETTINGS: The
      study was carried out at the outpatient palliative care center. DESIGN AND
      SUBJECTS: Retrospective review of 60 consecutive patient charts was done where
      the patient had initially scored the ESAS. The physician looked at this scoring
      on the ESAS and went back to the patient to do the scoring again to see if the
      patient had scored it in the way it was intended to be scored. The same physician
      did the assessment on all of the patients. OUTCOME MEASURES: Level of agreement
      (weighted kappa) before versus after the physician visit; Screening performance
      of patient completed ESAS for mild and moderate symptom intensity. RESULTS:
      Complete agreement ranged from 58% (sleep) to 82% (well-being); the weighted
      kappa ranged from 0.49 (drowsiness) to 0.78 (well-being). There was more
      agreement for symptoms such as dyspnea, nausea, anxiety, and depression and less
      agreement for symptoms such as lack of sleep and lack of appetite. The screening
      performance of the initial patient self assessment showed less sensitivity for
      nausea, drowsiness if the intensity was mild and less sensitivity for pain,
      nausea, anxiety, and drowsiness if the intensity was moderate. CONCLUSIONS:
      Vigilance needs to be maintained about the ESAS scores done by the patients
      particularly for symptoms of sleep, appetite, and pain. There is a likelihood of
      error if doctors or nurses do not routinely check the way patients have completed
      the assessment form. More research is needed to determine the best way to teach
      patients how to minimize errors in self-reporting of symptoms.

PMID- 17040145
TI  - Racial differences in next-of-kin participation in an ongoing survey of
      satisfaction with end-of-life care: a study of a study.
AB  - Despite disparities in health care access and quality, African Americans are
      underrepresented in many areas of clinical investigation, including research in
      end-of-life care. Because of the importance of surrogate reports in assessing the
      quality of end-of-life care, this study examined racial differences in next-of
      kin participation in an ongoing study of satisfaction with end-of-life care. The
      parent study includes after-death interviews with next-of-kin of elderly African
      Americans and Caucasians who died at Duke Hospital. This analysis included next
      of-kin of elders who died at Duke Hospital from December 1, 2003 to December 31,
      2004. During this period, there were 471 decedents whose next-of-kin were
      eligible for participation. Of these, 133 (28%) were African American and 338
      (72%) were Caucasian. There were no racial differences in completion, contact, or
      overall response rates. Of those contacted, 39.8% of African Americans and 37.8%
      of Caucasians completed the study. In multivariate analysis, only the
      relationship of the next-of-kin to the decedent was an independent predictor of
      study completion. Children of decedents were significantly more likely to
      participate than spouses (odds ratio [OR] 2.1 [1.14, 3.86]). In this analysis,
      next-of-kin of African American and Caucasian decedents were equally likely to
      participate in an after-death interview assessing satisfaction with end-of-life
      care. The use of racially concordant interviewers, subject identification with
      the institution, and the absence of socioeconomic constraints may partly explain
      these findings. Given the growing diversity of the U.S. population, researchers
      in end-of-life care must use strategies aimed at recruiting racially and
      ethnically diverse samples.

PMID- 17040144
TI  - Use of Palliative Performance Scale in end-of-life prognostication.
AB  - BACKGROUND: Current literature suggests clinicians are not accurate in
      prognostication when estimating survival times of palliative care patients. There
      are reported studies in which the Palliative Performance Scale (PPS) is used as a
      prognostic tool to predict survival of these patients. Yet, their findings are
      different in terms of the presence of distinct PPS survival profiles and
      significant covariates. OBJECTIVE: This study investigates the use of PPS as a
      prognostication tool for estimating survival times of patients with life-limiting
      illness in a palliative care unit. These findings are compared to those from
      earlier studies in terms of PPS survival profiles and covariates. METHODS: This
      is a retrospective cohort study in which the admission PPS scores of 733
      palliative care patients admitted between March 3, 2000 and August 9, 2002 were
      examined for survival patterns. Other predictors for survival included were age,
      gender, and diagnosis. RESULTS: Study findings revealed that admission PPS score
      was a strong predictor of survival in patients already identified as palliative,
      along with gender and age, but diagnosis was not significantly related to
      survival. We also found that scores of PPS 10% through PPS 50% led to distinct
      survival curves, and male patients had consistently lower survival rates than
      females regardless of PPS score. CONCLUSION: Our findings differ somewhat from
      earlier studies that suggested the presence of three distinct PPS survival
      profiles or bands, with diagnosis and noncancer as significant covariates. Such
      differences are likely attributed to the size and characteristics of the patient
      populations involved and further analysis with larger patient samples may help
      clarify PPS use in prognosis.

PMID- 17040146
TI  - Psychometric characteristics of a quality of communication questionnaire
      assessing communication about end-of-life care.
AB  - The importance of good clinician-patient communication to quality end-of-life
      care has been well documented yet there are no validated measures that allow
      patients to assess the quality of this communication. Using a sample of hospice
      patients (n = 83) and patients with chronic obstructive pulmonary disease (COPD)
      (n = 113), we evaluated the psychometric characteristics of a 13-item patient
      centered, patient-report questionnaire about the quality of end-of-life
      communication (QOC). Our purpose was to explore the measurement structure of the
      QOC items to ascertain if the items represent unitary or multidimensional
      constructs and to describe the construct validity of the QOC score(s). Analyses
      included: principal component analyses to identify scales, internal consistency
      analyses to demonstrate reliability, and correlational and group comparisons to
      support construct validity. Findings support the construction of two scales: a
      six-item "general communication skills" scale and a seven-item, "communication
      about end-of-life care" scale. The two scales meet standards of scale
      measurement, including good factor convergence (values >or= 0.63) and
      discrimination (values different >or= 0.25), percent of variance explained
      (69.3%), and good internal consistency (alpha >or= 0.79). The scales' construct
      validity is supported by significant associations (p <or= 0.01) with items
      assessing overall quality of doctor communication and quality of care, number and
      type of end-of-life discussions, and doctor's awareness of patient's treatment
      preferences. The general communication skills scale correlates more strongly with
      the general communication items while the communication about end-of-life care
      scale correlates more strongly with items addressing end-of-life topics. While
      further validation studies are needed, this assessment of the QOC represents an
      important step toward providing a measure of the quality of end-of-life
      communication.

PMID- 17040147
TI  - Differences in veterans' and nonveterans' end-of-life preferences: a pilot study.
AB  - BACKGROUND: Investigators conducting focus groups on end-of-life preferences
      noted that veterans voiced opinions that strongly differed from those of
      nonveterans. OBJECTIVE: The objective of this study was to further explore
      differences between veterans' and nonveterans' end-of-life preferences. METHODS:
      Ten focus groups and a pilot survey were conducted. SETTING AND SAMPLE: The focus
      groups consisted of Arab Muslims, Arab Christians, Hispanics, blacks, and whites
      stratified by gender (n = 73). Fifteen male veterans were included across all
      five racial groups. MEASURES: A moderator discussion guide was used to lead the
      focus groups and a pilot survey asked about demographic information and end-of
      life preferences. RESULTS: Veterans were more likely to be married (p < 0.05) and
      less connected to their cultural group (p < 0.05) than nonveterans. The focus
      group results indicated that veterans in this study were more likely to oppose
      the use of heroic measures compared to nonveterans. More so than nonveterans,
      veterans felt that their doctors should be frank and open (p < 0.05) were
      strongly in favor of do-not-resuscitate (DNR) orders (p < 0.10), yet were less
      likely to have a proxy (p < 0.10) or durable power of attorney p < 0.01).
      Comparing end-of-life preferences, veterans felt less strongly than nonveterans
      about remembering personal accomplishments (p < 0.05), being listened to (p <
      0.05), being with friends (p < 0.01), or being comfortable with their nurse (p <
      0.05), but did want to be around their pets at the end of life p < 0.10).
      IMPLICATIONS: The Department of Veterans Affairs is in a unique position to
      improve endof- life care for veterans. Providing end-of-life care that is
      congruent with the veteran's wishes can improve satisfaction and increase cost
      effectiveness by eliminating unacceptable services.

PMID- 17040148
TI  - Spiritual pain among patients with advanced cancer in palliative care.
AB  - BACKGROUND: The large body of empirical research suggesting that patients'
      spiritual and existential experiences influence the disease process has raised
      the need for health care professionals to understand the complexity of patients'
      spiritual pain and distress. OBJECTIVE: The current study explores the
      multidimensional nature of spiritual pain, in patients with end-stage cancer, in
      relation to physical pain, symptom severity, and emotional distress.
      DESIGN/MEASUREMENTS: The study combines a quantitative evaluation of
      participants' intensity of spiritual pain, physical pain, depression, and
      intensity of illness, with a qualitative focus on the nature of patients'
      spiritual pain and the kinds of interventions patients believed would ameliorate
      their spiritual pain. SETTING/SUBJECTS: Fifty-seven patients with advanced stage
      cancer in a palliative care hospital were interviewed by chaplains. RESULTS:
      Overall, 96% of the patients reported experiencing spiritual pain, but they
      expressed it in different ways: (1) as an intrapsychic conflict, (2) as
      interpersonal loss or conflict, or (3) in relation to the divine. Intensity of
      spiritual pain was correlated with depression (r = 0.43, p < 0.001), but not
      physical pain or severity of illness. The intensity of spiritual pain did not
      vary by age, gender, disease course or religious affiliation. CONCLUSIONS: Given
      both the universality of spiritual pain and the multifaceted nature of pain, we
      propose that when patients report the experience of pain, more consideration be
      given to the complexity of the phenomena and that spiritual pain be considered a
      contributing factor. The authors maintain that spiritual pain left unaddressed
      both impedes recovery and contributes to the overall suffering of the patient.

PMID- 17040149
TI  - Factors related to truth-telling practice of physicians treating patients with
      cancer in Turkey.
AB  - BACKGROUND: In the practice of oncology, effective communication between
      physician and patient is very important. Although many studies have indicated
      that a large majority of physicians, especially from Western countries, tell the
      truth about diagnosis and prognosis, little is known about attitudes of
      physicians in Turkey toward truth-telling. OBJECTIVE: In this study, we tried to
      determine the truth-telling practice of physicians and explore potential related
      factors with a self-reported questionnaire. DESIGN: Using a questionnaire, 131
      cancer specialists were interviewed during the 15th National Oncology Meeting in
      April 2003. RESULTS: The percentage of physicians who never, rarely, generally,
      and always prefer truthtelling about a cancer diagnosis were 9%, 39%, 45%, and
      7%, respectively. In univariate logistic regression analysis for the truth
      telling practice, significant variables included "do not tell" requests from
      family, experiences from medical training and clinical practice, and medical
      specialty. In the multivariate analysis, "do not tell" requests from relatives
      and medical training factors retained their significance. CONCLUSION:
      Professional training in breaking bad news is important and is associated with
      the self-reported truth-telling practices of physicians.

PMID- 17040150
TI  - Maslow's hierarchy of needs: a framework for achieving human potential in
      hospice.
AB  - Although the widespread implementation of hospice in the United States has led to
      tremendous advances in the care of the dying, there has been no widely accepted
      psychological theory to drive needs assessment and intervention design for the
      patient and family. The humanistic psychology of Abraham Maslow, especially his
      theory of motivation and the hierarchy of needs, has been widely applied in
      business and social science, but only sparsely discussed in the palliative care
      literature. In this article we review Maslow's original hierarchy, adapt it to
      hospice and palliative care, apply the adaptation to a case example, and then
      discuss its implications for patient care, education, and research. The five
      levels of the hierarchy of needs as adapted to palliative care are: (1)
      distressing symptoms, such as pain or dyspnea; (2) fears for physical safety, of
      dying or abandonment; (3) affection, love and acceptance in the face of
      devastating illness; (4) esteem, respect, and appreciation for the person; (5)
      selfactualization and transcendence. Maslow's modified hierarchy of palliative
      care needs could be utilized to provide a comprehensive approach for the
      assessment of patients' needs and the design of interventions to achieve goals
      that start with comfort and potentially extend to the experience of
      transcendence.

PMID- 17040151
TI  - Perceptions of the term palliative care.
AB  - OBJECTIVES: To assess parents' and health care providers' perceptions of the name
      and description of a pediatric palliative care (PPC) program. METHODS: Survey
      conducted at three pediatric health care sites; asked respondents (parents and
      staff) about their likelihood to use a program identified either as palliative
      care or supportive care, as well as their understanding and feelings about the
      program before and after reading a program description. RESULTS: Response rate
      was 89% (195/220); 184 were considered evaluable. Parent respondents in the
      supportive care group scored significantly higher (Mann-Whitney test, p = 0.003)
      on "likelihood to use program" (mean score, 4.22, n = 60) than those in the
      palliative care group (mean score, 3.58, n = 45) before each read the program
      description. However, this group difference disappeared (p = 0.582) after reading
      the description (mean scores 4.50, 4.38, respectively; n = 48, n = 40,
      respectively). The name palliative care evoked more negative emotions compared to
      the supportive care name in parents, and reading the program description led to
      more positive feelings. In staff, reading the program description significantly
      increased likelihood to use the program for those in the Palliative Care group
      only (4.22 to 4.44; p < 0.05; n = 41). Staff also had more positive feelings
      about the program called supportive care, and rated this name best most
      frequently. CONCLUSION: Better definition of and explanation to families and
      health care providers about what palliative care programs offer may improve
      perceptions about palliative care and increase program utilization.

PMID- 17040152
TI  - Physicians' opinions on palliative care and euthanasia in the Netherlands.
AB  - BACKGROUND: In recent decades significant developments in end-of-life care have
      taken place in The Netherlands. There has been more attention for palliative care
      and alongside the practice of euthanasia has been regulated. OBJECTIVE: The aim
      of this paper is to describe the opinions of physicians with regard to the
      relationship between palliative care and euthanasia, and determinants of these
      opinions. DESIGN: Cross-sectional. SETTING/SUBJECTS: Representative samples of
      physicians (n = 410), relatives of patients who died after euthanasia and
      physician-assisted suicide (EAS; n = 87), and members of the Euthanasia Review
      Committees (ERCs; n = 35). MEASUREMENTS: Structured interviews with physicians
      and relatives of patients, and a written questionnaire for the members of the
      ERCs. RESULTS: Approximately half of the physicians disagreed and one third
      agreed with statements describing the quality of palliative care in The
      Netherlands as suboptimal and describing the expertise of physicians with regard
      to palliative care as insufficient. Almost two thirds of the physicians disagreed
      with the suggestion that adequate treatment of pain and terminal care make
      euthanasia redundant. Having a religious belief, being a nursing home physician
      or a clinical specialist, never having performed euthanasia, and not wanting to
      perform euthanasia were related to the belief that adequate treatment of pain and
      terminal care could make euthanasia redundant. CONCLUSION: The study results
      indicate that most physicians in The Netherlands are not convinced that
      palliative care can always alleviate all suffering at the end of life and believe
      that euthanasia could be appropriate in some cases.

PMID- 17040153
TI  - Closing the Schiavo case: an analysis of legal reasoning.
AB  - The conflict surrounding Terri Schiavo, whom Florida's courts had determined
      wished not to be kept alive in a persistent vegetative state, played out on a
      national stage. The dispute between Schiavo's husband and parents engulfed
      America's legislative, executive, and judicial systems, raising profound
      questions about the laws and policies that govern advance directives. In this
      paper, we offer an analysis of the legal reasoning in Schiavo and offer
      predictions about the case's likely impact on law and policy in the future. We
      reviewed an extensive collection of case materials that included consensus
      definitions of persistent vegetative state, media reports, court decisions and
      briefs, legal chronologies, guardian reports, and Schiavo's autopsy report. We
      also reviewed cases cited as sources for legal reasoning used in Schiavo,
      including Quinlan, Cruzan, and Browning. We also examined the political,
      cultural, and media factors that affected the conflict. Based upon these reviews,
      we identified the legal reasoning that decided the Schiavo conflict. We found
      that Florida's constitutional right to privacy, a principle that shaped the
      Florida statutory and case law, guided the courts' consistent rulings. The
      conflict that characterized the case reflected profound differences in American
      politics rather than a failure of the medical and/or legal systems. The outcome
      of the Schiavo case remained consistent with established Florida statutory and
      case law, and honored Terri Schiavo's state constitutional right to privacy.
      Although Schiavo may not affect advance directive law and policy in palliative
      medicine immediately, evidence suggests it has already increased interest in
      creating living wills.

PMID- 17040154
TI  - Preparing caregivers for the death of a loved one: a theoretical framework and
      suggestions for future research.
AB  - Caring for a terminally ill loved one and the death of that person are two of the
      most stressful human experiences. Recent research suggests that a substantial
      number of caregivers are unprepared for the death and that these caregivers may
      be at greater risk of psychological distress. The literature on preparedness and
      mental health, however, is in its infancy. The purpose of this paper, therefore,
      is to summarize the literature in order to stimulate discussion and research on
      preparedness. It is our view that preparedness for the death of a loved one is an
      important contributor to caregiver well-being and bereavement outcomes and that
      more work in this area is needed in order to improve the care provided to
      caregivers of seriously or terminally ill patients. We briefly review the
      literature on preparedness, present a theoretical model delineating the
      relationships between preparedness, caregiver-health care provider communication,
      and caregiver well-being, and provide suggestions for future research.

PMID- 17040155
TI  - Editorial: caring for caregivers: the essence of palliative care.

PMID- 17040156
TI  - Caregiving at the end of life.
AB  - This paper provides a review of family caregiving for adult patients with
      serious, lifethreatening illness. Areas covered include the (1) epidemiology of
      family caregiving, (2) cross-cultural issues in caregiving, (3) impact of
      caregiving on families, (4) similarities and differences involved in providing
      care for patients with various illnesses, and (5) interventions for family
      caregivers. The importance of family caregiving to palliative care practice is
      emphasized.

PMID- 17040157
TI  - Update on bereavement research: evidence-based guidelines for the diagnosis and
      treatment of complicated bereavement.
AB  - The past decade has witnessed considerable growth in the evidence-base from which
      clinical recommendations for bereavement care can be made. Research now provides
      guidance to assist clinicians in: a) recognizing differences between complicated
      and uncomplicated bereavement reactions, b) identifying risk factors that may
      make certain individuals more vulnerable to bereavement-related complications, c)
      appreciating and monitoring for potential adverse outcomes associated with
      bereavement and d) taking actions to prevent or minimize maladjustment to the
      loss. In this article we distinguish between the course of normal grief and
      abnormally prolonged, or complicated grief; clarify distinctions between
      Complicated Grief Disorder and other mental disorders secondary to bereavement;
      review outcomes associated with Complicated Grief Disorder; describe research on
      resilience in bereavement; present findings on stigmatization and the use of
      mental health services among recently bereaved persons; and summarize where the
      field is with respect to establishing the efficacy and effectiveness of
      bereavement interventions. Promising new psychotherapies for Complicated Grief
      Disorder have shown clinical efficacy. Nevertheless, further research is needed
      to enhance the detection of vulnerable bereaved persons, to promote resilience
      following significant interpersonal loss, and to tailor interventions to address
      the attachment issues that lie at the heart of this disorder.

PMID- 17040158
TI  - Palliative care and intensive care unit care: preadmission assessment #122.

PMID- 17040159
TI  - Palliative care and intensive care unit care: daily intensive care unit care plan
      checklist #123.

PMID- 17040162
TI  - Treatment of fatigue: modafinil, methylphenidate, and goals of care.

PMID- 17040167
TI  - Intravenous fluids and end-of-life care.

PMID- 17040170
TI  - Remodeling and vascular spaces in bone.
AB  - In recent years, we have come to appreciate that the close association between
      bone and vasculature plays a pivotal role in the regulation of bone remodeling
      and fracture repair. In 2001, Hauge et al. characterized a specialized vascular
      structure, the bone remodeling compartment (BRC), and showed that the outer
      lining of this compartment was made up of flattened cells, displaying all the
      characteristics of lining cells in bone. A decrease in bone turnover leads to a
      decrease in surfaces covered with remodeling compartments, whereas increased
      turnover causes an increase. Immunoreactivity for all major osteotropic growth
      factors and cytokines including osteoprotegerin (OPG) and RANKL has been shown in
      the cells lining the BRC, which makes the BRC the structure of choice for
      coupling between resorption and formation. The secretion of these factors inside
      a confined space separated from the bone marrow would facilitate local regulation
      of the remodeling process without interference from growth factors secreted by
      blood cells in the marrow space. The BRC creates an environment where cells
      inside the structure are exposed to denuded bone, which may enable direct
      cellular interactions with integrins and other matrix factors known to regulate
      osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC
      also constitutes an ideal environment for the seeding of bone metastases, known
      to have high affinity for bone matrix. Reduction in BRC space brought about by
      antiresorptive therapies such as bisphosphonates reduce the number of skeletal
      events in advanced cancer, whereas an increase in BRC space induced by remodeling
      activators like PTH may increase the bone metastatic burden. The BRC has only
      been characterized in detail in trabecular bone; there is, however, evidence that
      a similar structure may exist in cortical bone, but further characterization is
      needed.

PMID- 17040173
TI  - Parent suicide: pathways of effects into the third generation.
AB  - There is a slim, slowly emerging literature addressing the impact of parent
      suicide upon children. By contrast with some other potentially pathogenic
      contexts for children (e.g., physical abuse), there has been virtually no
      exploration of the effect of a parent's suicide upon his or her children's
      parenting, that is, the transmission into a third generation of the sequelae of
      the original parent suicide. Based primarily on clinical and preventive work with
      adult "children of suicide" and their families, this paper begins to map some of
      the paths, direct and transparent or subterranean and disguised, that such
      experiences take into further generations. Patterns described include massive
      indulgence, communication of dire expectations, vicissitudes of family secrets,
      life-blanching living down the shame, defensive barriers against depressive
      affects, as well as dread-filled avoidance of producing a third generation.

PMID- 17040172
TI  - Allostatic load in women with and without PTSD symptoms.
AB  - Allostatic load (AL) is the term used to describe cumulative physiological wear
      and tear that results from repeated efforts to adapt to stressors over time.
      Operationalized as a composite index of biological risk factors (e.g., blood
      pressure, cholesterol, glycosylated hemoglobin, and cortisol, norepinephrine, and
      epinephrine), AL has been shown to increase with age, predict long-term morbidity
      and mortality among the elderly, and be associated with low parent education in a
      large adolescent sample. However, AL has not yet been studied in samples with
      putative "high stress" or posttraumatic stress disorder (PTSD). Accordingly, AL
      was measured in women with high acute and chronic stress: mothers of pediatric
      cancer survivors with and without PTSD and control mothers of healthy children.
      AL emerged in a "dose-dependent" ranking from high to low: cancer mothers meeting
      all criteria for PTSD, cancer mothers with no or low symptoms, and control
      mothers, respectively (p < .001). Effects were not altered by self-reported sleep
      quality or substance use (tobacco, caffeine, alcohol, or drugs) and remained
      significant when analyzing AL without cortisol or catecholamines. Results
      indicate elevated AL can be detected in relatively young women with high stress
      histories and particularly those with PTSD. Future prospective studies must
      evaluate whether this pattern represents an accelerated aging process and
      increased risk of disease.

PMID- 17040174
TI  - Disgust and obsessive-compulsive disorder: an update.
AB  - In this paper, we review the growing body of literature investigating the
      association between obsessive-compulsive disorder (OCD) and the emotion of
      disgust. Initially studied with regard to specific phobias, the potential role of
      disgust responses in contamination concerns has led researchers to investigate
      possible associations between disgust and OCD symptoms. The literature on disgust
      sensitivity in OCD is reviewed. Studies of disgust recognition in OCD and
      research using neuroimaging methods are then summarized. We suggest that disgust
      has a moderate association with OCD symptoms, particularly those which are
      contamination-based or which have a religious focus. Evidence for a disgust
      recognition deficit in patients with OCD is lacking; however, neuroimaging
      findings have confirmed hypothesized associations between contamination-focused
      OCD and the insula cortex, which has been implicated in disgust processing.
      Finally, treatment implications are discussed, and suggestions are made for
      further research.

PMID- 17040175
TI  - Job termination among individuals with severe mental illness participating in a
      supported employment program.
AB  - This study, which explored job terminations among 60 individuals with severe
      mental illness participating in a supported employment program in Hong Kong, used
      the Chinese Job Termination Interview that was validated and translated from the
      Job Termination Interview (JTI; Becker, Drake, Bond et al., 1988). More than half
      of the job terminations (53%) were unsatisfactory which included dissatisfaction
      with job (44%) and lack of interest (22%). Modification of work schedules and
      provision of adequate supervision and coaching at the workplace were identified
      as necessary job accommodations. Similarities and differences of findings were
      compared with overseas studies. Possible improvement of current supported
      employment program was discussed.

PMID- 17040176
TI  - Treatment compliance among patients with personality disorders receiving group
      psychotherapy: what are the roles of interpersonal distress and cohesion?
AB  - It is often assumed that patients with personality disorders have worse
      compliance in psychotherapy (i.e., attend fewer sessions) than patients without
      personality disorders. Such an assumption can have negative consequences for the
      treatment of patients with personality disorders. It also denies the presence of
      variability in session attendance among patients with personality disorders.
      Research that attempts to identify the factors that are associated with
      variability in session attendance among patients with personality disorders is
      needed. The present study examined the role of interpersonal distress as a
      predictor of session attendance for patients with personality disorders (n = 72)
      in two different forms of group psychotherapy (interpretive, supportive). The
      study also investigated whether patients' cohesion to their group mediated the
      effect of interpersonal distress on attendance. Findings indicated that
      interpersonal distress had a strong, direct association with attendance in
      supportive group therapy, but minimal association in interpretive group therapy.
      High levels of interpersonal distress were associated with higher attendance in
      supportive therapy. Furthermore, cohesion to the group accounted for about two
      thirds of the effect of interpersonal distress on attendance in supportive group
      therapy, thus providing compelling evidence for its role as a mediator. Possible
      explanations and clinical implications of these findings are discussed.

PMID- 17040180
TI  - The ethical group psychotherapist.
AB  - Group psychotherapists in their everyday practice confront a series of ethical
      problems, some of which rise to the level of ethical dilemmas. This two-part
      special series will address how the group psychotherapist can address these
      problems and dilemmas in a way that leads to an ethical course of conduct. This
      article introduces the series by examining ethical principles and decision-making
      processes that are relevant to the wide range of issues that confront the group
      psychotherapist. The article also considers the person of the group
      psychotherapist him or herself and notes that certain personal qualities might
      create a foundation for ethical thinking and behavior.

PMID- 17040181
TI  - Ethical issues in record keeping in group psychotherapy.
AB  - This article discusses numerous ethical issues regarding the keeping of records
      in group psychotherapy, those activities that have to do with the creating,
      retaining, storing, releasing, and disposing of them. A central dilemma for the
      group therapist is whether to keep records separately for each individual group
      member or to keep one record for the group as a whole. Confidentiality of
      records, patient access, and release of information tend to be more complex
      issues for group psychotherapists than for individual psychotherapists. Although
      notes written about the entire group may capture important themes, such notes can
      compromise the privacy and confidentiality of individual group members. An
      individual record for each patient is recommended.

PMID- 17040182
TI  - Informed consent in the practice of group psychotherapy.
AB  - Endorsed as part of ethical practice in group psychotherapy by professional
      organizations, informed consent is a process of communicating essential
      information about group treatment to patients so that they can make rational
      decisions about treatment-whether to enter and how to participate. Its benefits
      as well as necessary precautions are discussed. The design and implementation of
      the informed consent process for group is discussed in terms of who should obtain
      it, when it should occur, how it should be communicated, and what information
      should be considered for inclusion. Specific suggestions are included as well as
      a discussion of some potential ethical dilemmas.

PMID- 17040183
TI  - Confidentiality and privileged communication in group psychotherapy.
AB  - The concept of confidentiality is fundamental to all forms of psychotherapy. The
      idea of protecting confidential material goes as far back as the Hippocratic Oath
      in ancient Greek history. Centuries later, authors continue to assert that "only
      by maintaining confidentiality can the essential groundwork of trust in treatment
      be developed" (Hough, 1992, p. 106). Others have even argued that without
      confidentiality, psychotherapy has no value (Epstein, Steingarten, Weinstein, &
      Nashel, 1977). Confidentiality in group psychotherapy is more complicated than in
      individual therapy because self-disclosure is at the core of group therapy and
      there are numerous people hearing the disclosures. Confidentiality in group
      therapy, once ignored in the literature on ethics, is gaining more attention as
      this modality becomes more widely practiced; so too is an acknowledgement that
      ethical dilemmas surrounding confidentiality in groups are commonplace. This
      article discusses the major considerations and dilemmas on confidentiality in
      group psychotherapy. We first review confidentiality broadly and discuss the
      ethical principles that are related to confidentiality. In the next section, we
      discuss the complexities of confidentiality in group psychotherapy. Finally, we
      review research on confidentiality in groups and describe common ethical
      dilemmas.

PMID- 17040184
TI  - Buried treasure: money, ethics, and countertransference in group therapy.
AB  - Exploring money in the context of group therapy highlights the powerful way that
      groups can magnify the most intimate and charged aspects of our patients as well
      as ourselves.A thorough self-examination that includes an ethical framework for
      decision-making about money matters can safeguard against problems resulting from
      therapists' and patients' unconscious relationship to money. This paper addresses
      the setting and raising of fees, pre-group evaluations, third-party payers,
      handling of payments and statements, as well as combined treatment. Special
      attention is paid to countertransference with an exploration of the particular
      difficulties inherent in reconciling one's identity as a healer with the business
      of clinical practice.

PMID- 17040185
TI  - A historical addendum to Billow's (2005) review of Lipgar and Pines' edited
      volumes on W.R. Bion.

PMID- 17040186
TI  - Group psychotherapy in psychiatric hospitals and clinics passes the 70-year mark.

PMID- 17040191
TI  - Complementary new approaches enable repositioning of failed drug candidates.
AB  - Until recently, safe drug candidates that failed in clinical trials were shelved
      as drug developers channelled resources to the next candidates in the pipeline.
      In the past few years, new technologies, improved genomic information and high
      throughput methods have made it possible to quickly and economically re-examine
      advanced drug candidates for therapeutic activity against other diseases. This
      development arrives at an opportune time, as pharmaceutical companies strive to
      fill sparse late-stage pipelines at the same time as keeping costs down.
      Specialised companies are emerging with new methods and a fresh point of view to
      assist pharmaceutical developers in turning failed drug candidates from one
      therapeutic area into successful treatments in another. This editorial introduces
      a series of papers to be published in Expert Opinion on Investigational Drugs,
      discussing discontinued drugs from 2005.

PMID- 17040192
TI  - Discontinued drugs in 2005: cardiovascular drugs.
AB  - This perspective describes cardiovascular compounds dropped from clinical
      development in 2005 and is the first in a series of papers to be published in
      Expert Opinion on Investigational Drugs, discussing discontinued drugs from that
      year. Discontinued candidates are described by the phase of development they
      reached, based on the information available from the Pharmaprojects database.
      Discontinued drugs in the atherosclerosis/dyslipidaemia area are discussed in
      more detail.

PMID- 17040193
TI  - Discontinued drugs in 2005: oncology drugs.
AB  - This perspective is the second in a series of papers discussing drugs dropped
      from development in 2005, of which 20 were being developed for cancer. Of these
      20, 60% were biological agents and included 3 cancer vaccine (e.g., Canvaxin) and
      2 antisense oligonucleotide (e.g., aprinocarsen sodium). Overall, 10 cancer drugs
      were discontinued in Phase I, 6 in Phase II and 4 at Phase III. This paper
      surveys drugs discontinued in the oncology arena in 2005 by stage of development
      and class of compound, suggesting some reasons for their failure.

PMID- 17040194
TI  - Developments in the treatment of candidiasis: more choices and new challenges.
AB  - The incidence of oesophageal candidiasis, candidaemia and disseminated
      candidiasis has increased dramatically. In addition to the amphotericin B
      formulations and fluconazole, the echinocandins anidulafungin, caspofungin and
      micafungin and the newer triazoles posaconazole and voriconazole are in the last
      stages of development and are becoming available for the management of
      candidiasis. This review presents these new agents and addresses their role in
      the treatment of candidiasis. All new antifungal agents exhibit potent activity
      against Candida spp. and echinocandins are fungicidal against most Candida spp.
      but appear to be less potent against certain species, such as Candida
      parapsilosis and C. guilliermondii. Systemic antifungal therapy can now be
      individualised based on the severity of the infection, comorbid conditions and
      the Candida spp. causing the infection. Studies are needed to investigate the
      possible development of resistance and the efficacy of these antifungal agents
      against the more resistant Candida spp.

PMID- 17040195
TI  - Cholesterol absorption inhibitors as a therapeutic option for
      hypercholesterolaemia.
AB  - The development of cholesterol-lowering drugs (including a variety of statins,
      bile acid-binding resins and recently discovered inhibitors of cholesterol
      absorption) has expanded the options for cardiovascular prevention. Recent
      treatment guidelines emphasise that individuals at substantial risk for
      atherosclerotic coronary heart disease should meet defined targets for LDL
      cholesterol concentrations. Combination therapy with drugs that have different or
      complementary mechanisms of action is often needed to achieve lipid goals.
      Existing approaches to the treatment of hypercholesterolaemia are still
      ineffective in halting the progression of coronary artery disease in some
      patients despite combination therapies. Other patients are resistant to
      conventional drug treatment and remain at high risk for the development and
      progression of atherosclerotic cardiovascular disease and alternative approaches
      are needed. The discovery and development of ezetimibe (a novel, selective and
      potent cholesterol absorption inhibitor) has advanced the treatment of
      hypercholesterolaemia. New agents including the phytostanol preparation FM-VP4
      and inhibitors of acyl coenzyme A:cholesterol acyltransferase, the apical Na(+)
      dependent bile acid transporter and microsomal triglyceride transfer protein may
      also play a future role in combination therapy. This review focuses on the recent
      progress in the molecular mechanisms of intestinal cholesterol absorption and
      transport, and novel therapeutic approaches to inhibit the cholesterol absorption
      process.

PMID- 17040196
TI  - Current pharmacotherapy for the treatment of crescentic glomerulonephritis.
AB  - Glomerulonephritis is an important cause of end-stage renal disease. Crescentic
      glomerulonephritis is the most severe form of glomerulonephritis and, if
      untreated, patients will develop renal failure within days or weeks of diagnosis.
      Current immunotherapy consists of corticosteroids, cytotoxic drugs and plasma
      exchange. Challenges include minimising toxicity of therapy, preventing relapse
      in antineutrophil cytoplasmic antibodies-associated vasculitis and finding an
      effective treatment for crescentic IgA nephropathy. There are opportunities for
      more specific therapies using monoclonal antibodies to T cells (and their co
      stimulatory receptors), B cells and cytokines, or pharmacological inhibitors of
      signal transduction. Their efficacy and safety remain to be established with
      controlled clinical trials. Recent development of urinary cytokine measurement
      provides a noninvasive biomarker of renal disease activity, which is useful in
      monitoring response to therapy and assessing prognosis.

PMID- 17040197
TI  - Recent advances in neuroprotection for treating traumatic brain injury.
AB  - The fact that traumatic brain injury is the leading cause of death and disability
      in the most active population (< 45 years of age) of industrialised countries
      underscores the need for intensified efforts to define and implement effective
      neuroprotective strategies. However, despite progressively growing knowledge on
      the mechanisms involved in the pathobiology of traumatic brain injury and
      promising preclinical findings, most of the neuroprotection trials have failed to
      deliver the expected level of beneficial effects. Some of the possible reasons
      underlying the lack of success of these clinical trials are addressed in this
      review, which describes some of the most promising and/or controversial ongoing
      clinical trials from their pathophysiological basis. In addition, new
      neurobiological findings and their consequence for novel neuroprotective
      approaches are discussed.

PMID- 17040198
TI  - Catalytic antioxidants to treat amyotropic lateral sclerosis.
AB  - Catalytic antioxidants are comprised of specialised classes of organometallic
      complexes that can catalyse the decomposition of injurious biological oxidants.
      These complexes have been shown to prevent the formation of several oxidative
      markers in spinal cord of G93A amyotropic lateral sclerosis mice and markedly
      extend survival, even when administered at symptom onset; however, it is now
      clear that some complexes lacking in antioxidant activity are also protective.
      New proteomics data suggest that these complexes also induce a broad spectrum of
      endogenous cellular defense mechanisms. The combination of antioxidant and
      adaptive resistance effects may explain the remarkable potency of these compounds
      and may also suggest wide applicability for them in a number of neurodegenerative
      diseases.

PMID- 17040199
TI  - Pancreatic cancer: a review of recent advances.
AB  - Pancreatic cancer is one of the most common causes of cancer-related death.
      Despite the advances of the molecular pathogenesis, pancreatic cancer remains a
      major unsolved health problem. Overall, the 5-year survival rate is < 5% and only
      approximately 20% of the 10% of patients with resectable disease survive 5 years.
      Recently, the European Study Group for Pancreatic Cancer 1 trial demonstrated
      substantially increased survival from adjuvant chemotherapy with 5-fluorouracil
      folinic acid and preliminary data showed prolonged disease-free survival from
      adjuvant gemcitabine. Current palliative therapeutic approaches mostly focused on
      evaluating chemotherapy regimens in which gemcitabine is combined with a second
      cytotoxic agent. Recently, large randomised trials of combinations of gemcitabine
      with either capecitabine or with erlotinib demonstrated prolonged survival and 1
      year survival rates of approximately 25%. The advance of molecular biology has
      led to the elucidation of molecular events that are important for pancreatic
      carcinogenesis and has provided a foundation for the development of novel
      chemotherapeutic and biological agents that appear to be promising and are likely
      to play a future role in the treatment of patients with advanced pancreatic
      cancer.

PMID- 17040200
TI  - Development of new cancer therapeutic agents targeting mitosis.
AB  - Targeting cellular proliferation persists as a mainstay of cancer therapeutic
      strategy. Although microtubule-targeting drugs (such as taxanes and vinca
      alkaloids) have been used successfully in the clinic to treat a variety of
      cancers, they carry substantial liabilities that have spurred drug companies to
      aggressively pursue new tubulin-targeting drug candidates with improved efficacy
      and toxicity profiles. The recent discoveries of new mitotic targets for cancer
      therapy (such as kinesin spindle protein, Aurora kinases and Polo-like kinase-1)
      have also stimulated intense work focused on identifying novel antimitotic drugs
      directed at these new targets. A number of novel antimitotic drugs have
      demonstrated encouraging activity in preclinical models and have progressed into
      clinical development. This review focuses on selected new antimitotic drugs under
      evaluation in clinical trials.

PMID- 17040201
TI  - Novel therapies for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes
      significant morbidity and mortality. The pathogenesis outlined to date in RA
      consists of a cascade of pro-inflammatory cytokines and chemokines leading to the
      recruitment of inflammatory cells and the self perpetuation of inflammation,
      ultimately leading to cartilage and bone destruction. The dramatic progress in
      understanding the molecular immunology in RA has led to a transition from
      conventional treatment with aggressive immune suppression to targeted biological
      based therapies that control the inflammatory pathways associated with RA. This
      article reviews the current biological and small-molecule therapies approved for
      the treatment of RA and those in development, including antibodies, tolerising
      agents and vaccines.

PMID- 17040202
TI  - The histamine H4 receptor in autoimmune disease.
AB  - Histamine exerts its actions through four known receptors. The recently cloned
      histamine receptor, H4R, has been shown to have a role in chemotaxis and mediator
      release in various types of immune cells including mast cells, eosinophils,
      dendritic cells and T cells. H4R antagonists have been shown to have anti
      inflammatory properties and efficacy in a number of disease models, such as those
      for asthma and colitis in vivo. Recently, H4R antagonists have been developed
      with high receptor affinity and specificity, which make them good tools for
      further characterisation of the receptor in animal models and, eventually, in
      humans. Histamine and the cells that produce it, such as mast cells and
      basophils, have long been thought to be involved in allergic conditions but there
      has recently been recognition that they may also play a role in various
      autoimmune diseases. Given this and the fact that the H4R has function in mast
      cells, dendritic cells and T cells, antagonists for the receptor may be useful in
      treating autoimmune diseases in addition to allergy.

PMID- 17040203
TI  - Thiazolidinediones: potential as therapeutics for psoriasis and perhaps other
      hyperproliferative skin disease.
AB  - The thiazolidinediones constitute a family of synthetic compounds that act as
      high-affinity ligands for persoxisome proliferator-activated receptor-gamma (PPAR
      gamma), a member of the nuclear hormone receptor family. Although originally
      developed to facilitate glucose control in patients with Type 2 diabetes, a
      number of studies showed that these agents effectively inhibited epithelial cell
      proliferation and tissue inflammation. Many of the initial cell growth inhibition
      studies were conducted with malignant epithelial cells from various sites;
      however, in addition to malignant epithelial cells, other studies showed that
      rapidly proliferating epidermal keratinoctyes in culture were also sensitive to
      the growth-inhibiting action of these moieties. Additional studies subsequently
      demonstrated that some patients with plaque psoriasis responded to treatment with
      one or another member of the thiazolidinedione family. Due to the potential
      therapeutic benefit of these compounds in diseases such as psoriasis, studies
      have been conducted to elucidate mechanisms by which growth inhibition is
      achieved. Interference with a number of growth-influencing signalling pathways
      has been demonstrated. Of interest, some of the growth-inhibiting effects are
      seen under conditions in which PPAR-gamma activation may not be responsible for
      the activity. Based on therapeutic potential, additional ongoing studies are
      aimed at developing novel thiazolidinediones that may have better efficacy than
      the currently available agents. Other studies are aimed at identifying optimal
      ways to use these agents in the treatment of hyperplastic skin diseases such as
      psoriasis.

PMID- 17040204
TI  - Fentanyl buccal tablets.
AB  - Fentanyl buccal tablets (FBT) are designed to manage the breakthrough pain
      associated with chronic pain with an enhanced rate and extent of fentanyl
      absorption through the buccal mucosa. The formulation incorporates an
      effervescent reaction to produce large shifts in pH that enhance absorption.
      Results from studies of safety and tolerability have shown FBT to be effective
      and well tolerated in opioid-tolerant chronic pain patients. Adverse events were
      similar to those seen with other opioids and included nausea and somnolence.
      Adverse events were common but mild or moderate in most cases and did not cause a
      high drop-out rate. In addition to the treatment of breakthrough pain, FBT could
      be clinically efficacious for the treatment of brief, anticipated painful events.
      The abuse liability of FBT is unknown and caution should be used in prescribing
      FBT to patients with histories of substance abuse.

PMID- 17040205
TI  - Effects of lymphotoxin-alpha gene and galectin-2 gene polymorphisms on
      inflammatory biomarkers, cellular adhesion molecules and risk of coronary heart
      disease.
AB  - The pro-inflammatory cytokine LTA (lymphotoxin-alpha) has multiple functions in
      regulating the immune system and may contribute to inflammatory processes leading
      to CHD (coronary heart disease). The aim of the present study was to investigate
      whether the common C804A (resulting in a Thr(26)-->Asp amino acid substitution)
      and A252G polymorphisms of the LTA gene and the C3279T polymorphism of the
      galectin-2 (LGALS2) gene, which affects LTA secretion, are associated with
      inflammatory parameters and cell adhesion molecules, and whether these
      polymorphisms are related to CHD in American women and men. We conducted a
      prospective nested case-control study within the Nurses' Health Study and Health
      Professionals Follow-Up Study. Among participants free of cardiovascular disease
      at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow
      up respectively, and we matched controls 2:1 based on age and smoking. The LGALS2
      gene variant was significantly associated with a decreased risk of CHD in women
      [odds ratio (95% confidence interval), 0.70 (0.50-0.97); P=0.03]. In addition,
      the LGALS2 polymorphism was directly associated with CRP (C-reactive protein)
      levels in cases from both studies (P<0.05). The LTA gene polymorphisms were
      directly associated with levels of sTNFRs (soluble tumour necrosis factor
      receptors) and VCAM-1 (vascular cell adhesion molecule-1) in both women and men
      with CHD (P<0.05). However, no overall effect was demonstrated between LTA gene
      polymorphisms and risk of CHD.

PMID- 17040206
TI  - Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence
      in African trypanosomes.
AB  - In trypanosomes, the thioredoxin-type protein TXN (tryparedoxin) is a multi
      purpose oxidoreductase that is involved in the detoxification of hydroperoxides,
      the synthesis of DNA precursors and the replication of the kinetoplastid DNA.
      African trypanosomes possess two isoforms that are localized in the cytosol and
      in the mitochondrion of the parasites respectively. Here we report on the
      biological significance of the cTXN (cytosolic TXN) of Trypanosoma brucei for
      hydroperoxide detoxification. Depending on the growth phase, the concentration of
      the protein is 3-7-fold higher in the parasite form infecting mammals (50-100
      microM) than in the form hosted by the tsetse fly (7-34 microM). Depletion of the
      mRNA in bloodstream trypanosomes by RNA interference revealed the
      indispensability of the protein. Proliferation and viability of cultured
      trypanosomes were impaired when TXN was lowered to 1 muM for more than 48 h.
      Although the levels of glutathione, glutathionylspermidine and trypanothione were
      increased 2-3.5-fold, the sensitivity against exogenously generated H2O2 was
      significantly enhanced. The results prove the essential role of the cTXN and its
      pivotal function in the parasite defence against oxidative stress.

PMID- 17040207
TI  - Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and
      cGMP.
AB  - The Dictyostelium discoideum genome uncovers seven cyclic nucleotide PDEs
      (phosphodiesterases), of which six have been characterized previously and the
      seventh is characterized in the present paper. Three enzymes belong to the
      ubiquitous class I PDEs, common in all eukaryotes, whereas four enzymes belong to
      the rare class II PDEs that are present in bacteria and lower eukaryotes. Since
      all D. discoideum PDEs are now characterized we have calculated the contribution
      of each enzyme in the degradation of the three important pools of cyclic
      nucleotides: (i) extracellular cAMP that induces chemotaxis during aggregation
      and differentiation in slugs; (ii) intracellular cAMP that mediates development;
      and (iii) intracellular cGMP that mediates chemotaxis. It appears that each
      cyclic nucleotide pool is degraded by a combination of enzymes that have
      different affinities, allowing a broad range of substrate concentrations to be
      degraded with first-order kinetics. Extracellular cAMP is degraded predominantly
      by the class II high-affinity enzyme DdPDE1 and its close homologue DdPDE7, and
      in the multicellular stage also by the low-affinity transmembrane class I enzyme
      DdPDE4. Intracellular cAMP is degraded by the DdPDE2, a class I enzyme regulated
      by histidine kinase/phospho-relay, and by the cAMP-/cGMP-stimulated class II
      DdPDE6. Finally, basal intracellular cGMP is degraded predominantly by the high
      affinity class I DdPDE3, while the elevated cGMP levels that arise after receptor
      stimulation are degraded predominantly by a cGMP-stimulated cGMP-specific class
      II DdPDE5. The analysis shows that the combination of enzymes is tuned to keep
      the concentration and lifetime of the substrate within a functional range.

PMID- 17040208
TI  - Role of Ca2+ activation and bilobal structure of calmodulin in nuclear and
      nucleolar localization.
AB  - Ca2+ signalling to the nucleus is thought to occur by calmodulin entry into the
      nucleus where calmodulin has many functions. In the present study we have
      investigated the role of Ca2+ and the N- and C-terminal lobes of calmodulin in
      its subnuclear targeting by using fluorescently labelled calmodulin and its
      mutants and confocal microscopy. Our data show, first, that Ca2+ stimulation
      induces a reorganization of subnuclear structures to which apo-calmodulin can
      bind. Secondly, Ca2+-independent association of the C-terminal lobe is seen with
      subnuclear structures such as chromatin, the nuclear envelope and the nucleoli.
      Thirdly, Ca2+-dependent accumulation of both calmodulin and the C-terminal
      calmodulin lobe occurs in the nucleoli. The N-terminal lobe of calmodulin does
      not show significant binding to subnuclear structures although, similarly to the
      C-terminal lobe, it accumulates in the nucleoplasm of wheat germ agglutinin
      blocked nuclei suggesting that a facilitated nuclear export mechanism exists for
      calmodulin.

PMID- 17040209
TI  - Identification of a novel targeting sequence for regulated secretion in the
      serine protease inhibitor neuroserpin.
AB  - Ns (neuroserpin) is a member of the serpin (serine protease inhibitor) gene
      family that is primarily expressed within the central nervous system. Its
      principal target protease is tPA (tissue plasminogen activator), which is thought
      to contribute to synaptic plasticity and to be secreted in a stimulus-dependent
      manner. In the present study, we demonstrate in primary neuronal cultures that Ns
      co-localizes in LDCVs (large dense core vesicles) with the regulated secretory
      protein chromogranin B. We also show that Ns secretion is regulated and can be
      specifically induced 4-fold by secretagogue treatment. A novel 13-amino-acid
      sorting signal located at the C-terminus of Ns is identified that is both
      necessary and sufficient to target Ns to the regulated secretion pathway. Its
      deletion renders Ns no longer responsive to secretagogue stimulation, whereas PAI
      Ns [Ns (neuroserpin)-PAI-1 (plasminogen activator inhibitor-1) chimaera appending
      the last 13 residues of Ns sequence to the C-terminus of PAI-1] shifts PAI-1
      secretion into a regulated secretory pathway.

PMID- 17040211
TI  - Comparison of early and late toxic effects of sulfur mustard in Iranian veterans.
AB  - Sulfur mustard is an alkylating agent that reacts with ocular, respiratory,
      cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We
      compare these effects based on the experience in Iranian veterans exposed to the
      agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations
      of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness,
      lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory
      effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin
      lesions varied from erythema to bullous necrotization. Initial leukocytosis and
      lymphopenia returned to normal within four weeks in recovered patients, but
      marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic
      effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main
      respiratory complications were chronic obstructive pulmonary disease,
      bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin
      lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen
      of the severely intoxicated patients were diagnosed with delayed keratitis,
      having corneal vascularization, thinning, and epithelial defect. Respiratory
      complications exacerbated over time, while cutaneous and ocular lesions decreased
      or remained constant. Both the severity and frequency of bronchiectatic lesions
      increased during long-term follow-up. The only deteriorating cutaneous
      complication was dry skin. The maximum incidence of delayed kaeratitis was
      observed 15 to 20 years after initial exposure. Being suggested as the main cause
      ofassociated with malignancies and recurrent infections, natural killer cells
      were significantly lower 16 to 20 years after intoxication.

PMID- 17040210
TI  - BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in
      vitro and in vivo.
AB  - Hormones and growth factors induce the activation of a number of protein kinases
      that belong to the AGC subfamily, including isoforms of PKA, protein kinase B
      (also known as Akt), PKC, S6K p70 (ribosomal S6 kinase), RSK (p90 ribosomal S6
      kinase) and MSK (mitogen- and stress-activated protein kinase), which then
      mediate many of the physiological processes that are regulated by these
      extracellular agonists. It can be difficult to assess the individual functions of
      each AGC kinase because their substrate specificities are similar. Here we
      describe the small molecule BI-D1870, which inhibits RSK1, RSK2, RSK3 and RSK4 in
      vitro with an IC(50) of 10-30 nM, but does not signi-ficantly inhibit ten other
      AGC kinase members and over 40 other protein kinases tested at 100-fold higher
      concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol
      ester- and EGF (epidermal growth factor)-induced phosphoryl-ation of glycogen
      synthase kinase-3beta and LKB1 in human embry-onic kidney 293 cells and Rat-2
      cells. In contrast, BI-D1870 does not affect the agonist-triggered
      phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does
      not suppress the phorbol ester- or EGF-induced phosphorylation of CREB (cAMP
      response-element-binding protein), consistent with the genetic evidence
      indicating that MSK, and not RSK, isoforms mediate the mitogen-induced
      phosphorylation of this transcription factor.

PMID- 17040212
TI  - The established and emerging uses of aspirin.
AB  - In this paper, summary narratives on the established and emerging uses of aspirin
      are presented. On the former, aspirin is used to treat conditions such as
      headache and also reduce the risks associated with cardiovascular disease and
      also with pre-eclampsia. On the latter, aspirin might be taken more widely by
      individuals over 50 years, used as a dietary supplement to possibly reduce cancer
      risk and used post-transplant to improve organ survival. Aspirin will continue to
      be an important therapeutic agent and to generate considerable interest among the
      research community for the foreseeable future.

PMID- 17040213
TI  - New melanocortin 1 receptor binding motif based on the C-terminal sequence of
      alpha-melanocyte-stimulating hormone.
AB  - The C-terminal tripeptide of the alpha-melanocyte stimulating hormone (alpha
      MSH11-13) possesses strong antiinflammatory activity without known cellular
      target. In order to better understand the structural requirements for function of
      such motif, we designed, synthesized and tested out Trp- and Tyr-containing
      analogues of the alpha-MSH11-13. Seven alpha-MSH11-13 analogues were synthesized
      and characterized for their binding to the melanocortin receptors recombinantly
      expressed in insect (Sf9) cells, infected with baculovirus carrying corresponding
      MC receptor DNA. We also tested these analogues on B16-F1 mouse melanoma cells
      endogenously expressing the MC1 receptor for binding and for ability to increase
      cAMP levels as well as on COS-7 cells transfected with the human MC receptors.
      The data indicate that HS401 (Ac-Tyr-Lys-Pro-Val-NH2) and HS402 (Ac-Lys-Pro-Val
      Tyr-NH2) selectively bound to the MC1 receptor and stimulated cAMP generation in
      a concentration dependent way while the other Tyr- and Trp-containing alpha-MSH11
      13 analogues neither bound to MC receptors nor stimulated cAMP. We have thus
      identified new MC receptor binding motif derived from the C-terminal sequence of
      alpha-MSH. The tetrapeptides have novel properties as the both act via MC-ergic
      pathways and also carry the anti-inflammatory alpha-MSH11-13 message sequence.

PMID- 17040214
TI  - Mitochondrial uncoupling by the sulindac metabolite, sulindac sulfide.
AB  - Sulindac is a non-steroidal antiinflammatory drug (NSAID) known to inhibit
      cyclooxygenases (COX) 1 and 2, and at present of interest for cancer prevention.
      However, its therapeutic use has been limited by its toxicity to the
      gastrointestinal tract and liver. We address the effects of sulindac, of the
      pharmacologically inactive metabolite, sulindac sulfone, and of the
      pharmacologically active metabolite, sudindac sulfide, on isolated rat liver
      mitochondria and HepG2 cells. Sulindac sulfide, but not sulindac sulfone or
      sulindac itself, caused mitochondrial uncoupling, released preaccumulated Ca2+
      from the organelle, and decreased Hep-G2 cell viability in apparent association
      with cell ATP depletion resulting from mitochondrial uncoupling-associated
      membrane potential dissipation.

PMID- 17040215
TI  - Effect of caffeine intake 12 or 24 hours prior to melatonin intake and CYP1A2*1F
      polymorphism on CYP1A2 phenotyping by melatonin.
AB  - Earlier evidence suggests that melatonin is almost exclusively metabolised by
      CYP1A2 and could serve as a probe drug for CYP1A2 phenotyping. However, caffeine
      inhibits the metabolism of melatonin by CYP1A2 and dietary caffeine could be a
      potential confounder for the measurement of CYP1A2 activity with melatonin. We
      undertook a 3-phase cross-over study in 12 healthy volunteers to examine whether
      caffeine (200 mg single dose), taken 12 hr or 24 hr prior to melatonin intake,
      would affect the results of CYP1A2 phenotyping results as assessed by a spot
      sample melatonin concentration 1.5 hr after intake of 6 mg of melatonin orally.
      In addition we examined the influence of the CYP1A2*1F polymorphism on the
      phenotyping results by combining the present material with another 12 persons
      from a previous study. Caffeine, co-administered 12 or 24 hr prior to melatonin
      intake, did not have any significant effect on the 1.5 hr melatonin concentration
      (P=0.086 for ANOVA), but in two volunteers about 4 times increase in melatonin
      concentration was observed after caffeine intake 12 hr (but not 24 hr) before
      phenotyping with melatonin. Also, individuals homozygous for the CYP1A2*1A allele
      had clearly higher 1.5 hr melatonin concentration compared with the *1F/*1F or
      the *1F/*1A genotypes. Abstinence from caffeine for 24 hr prior to melatonin
      intake should be enough to overcome the possible confounding effect of caffeine
      on the CYP1A2 phenotyping with melatonin. Also, melatonin may be a sensitive
      probe to detect phenotypic differences with regard to CYP1A2*1F polymorphism.
      Melatonin might be, thus, advantageous for CYP1A2 phenotyping compared to the
      standard probe caffeine.

PMID- 17040216
TI  - Increased susceptibility to phenytoin teratogenicity: excessive generation of
      reactive oxygen species or impaired antioxidant defense?
AB  - Phenytoin is a human and animal teratogen. Accumulating evidence suggests that
      the teratogenicity is associated with a potential of phenytoin to cause embryonic
      cardiac arrhythmia and resultant generation of toxic reactive oxygen species via
      hypoxia-reoxygenation mechanisms. The A/J mouse is more susceptible to phenytoin
      teratogenicity than other mouse strains. The aim of this study was to investigate
      whether A/J mice have other antioxidant enzyme activities than C57BL/6J and CD-1
      mice. Also, strain differences in phenytoin effects on embryonic heart rate and
      rhythm were determined. Another objective was to determine whether a spin
      trapping agent with capacity to capture reactive oxygen species alter the
      developmental toxicity of phenytoin. Treatment with this agent resulted in a
      marked decrease in phenytoin teratogenicity, which supports the idea that
      reactive oxygen species are important mediators for the teratogenic action of
      phenytoin. The A/J mice embryos were most susceptible to the adverse cardiac
      effects of phenytoin and had the highest activity of superoxide dismutase and
      glutathione peroxidase, while the activity of catalase was the same in embryos of
      the three different strains. The high activities of antioxidant enzymes in the
      A/J stain indicate that the sensitivity to develop malformations is caused by
      excessive arrhythmia-related generation of reactive oxygen species rather than
      impaired antioxidant defense.

PMID- 17040217
TI  - Ranitidine in acute high-dose organophosphate exposure in rats: effect of the
      time-point of administration and comparison with pyridostigmine.
AB  - Weak and reversible inhibitors of cholinesterase, when co-administered in large
      doses, can act in a protective manner against more potent inhibitors such as
      organophosphates. The clinically widely used histamine type 2 (H2) receptor
      blocker ranitidine is among H2 blockers the most potent inhibitor of
      acetylcholinesterase but roughly three to four orders of magnitude less potent
      than paraoxon (an irreversible organophosphate esterase inhibitor) or
      pyridostigmine (a reversible carbamate esterase inhibitor). We have previously
      shown that in vitro ranitidine confers some protection against inhibition of
      cholinesterases by paraoxon and that in vivo it both increases the number of rats
      surviving an acute paraoxon exposure and also protects to some degree the
      cholinesterases from organophosphate inhibition. The purpose of the study was to
      compare in a prospective non-blinded study, in a rat model of acute high-dose
      paraoxon exposure, ranitidine with pyridostigmine either administered
      simultaneously or 30 min. before exposure. There were 36 rats in each of the 5
      groups. All substances were applied intraperitoneally. Additional analysis
      included data from a similar experiment carried out in 2005, in which 54 rats
      were exposed to paraoxon only (G1) and 54 to paraoxon+ranitidine simultaneously
      (G2). All groups (except controls; G6 & G7) received 1 micro Mol paraoxon
      (approximately LD75); groups 2-5 received in addition to paraoxon: G2: 50 micro
      Mol ranitidine within 1 min. of paraoxon, G3: 1 micro Mol pyridostigmine within 1
      min. of paraoxon, G4: 50 micro Mol ranitidine 30 min. before paraoxon, G5: 1
      micro Mol pyridostigmine 30 min. before paraoxon. Groups 6 & 7 received only
      ranitidine and pyridostigmine respectively, group G1 received only paraoxon.
      Mortality was recorded at 30 min., 1, 2, 3, 4, 24 and 48 hr. Mortality data were
      compared using Kaplan-Meier plots and logrank tests. No Bonferroni correction for
      multiple comparisons was applied and an alpha < or = 0.05 was considered
      significant. All statistical analysis was performed by using SPSS 12.0
      statistical software (SPSS Inc., Chicago, IL, USA). Simultaneous administration
      of ranitidine or pyridostigmine with paraoxon does not significantly affect
      mortality. Pretreatment (30 min. before) with both ranitidine or pyridostigmine
      statistically and significantly reduced mortality. When administered before
      paraoxon, pyridostigmine is statistically significantly superior to ranitidine.
      Both ranitidine and pyridostigmine are protective against acute paraoxon toxicity
      provided they are administered before paraoxon. Pyridostigmine results are
      statistically significantly superior to ranitidine (< or =0.05).

PMID- 17040218
TI  - Zidovudine inhibits protein kinase C activity in human chronic myeloid (K562)
      cells.
AB  - In this paper we show that human erythroleukaemia (K562) cells exhibited a
      significant inhibition of protein kinase C activity when cells were exposed to 40
      micro M zidovudine in a time interval of 5-180 min., whereas prolonged treatment
      (24 hr) was uneffective. The addition of an excess of thymidine (125:1, mol:mol),
      in the cell suspension with or without zidovudine fully restored the protein
      kinase C activity. Interestingly, either in cell homogenates and in commercially
      purified rat brain protein kinase C, both zidovudine and its monophosphate
      derivative, caused inhibition that was higher than in intact cells. This
      inhibition reached a maximal value of 45% when zidovudine or zidovudine
      monophosphate were incubated with the pure commercial enzyme and in this case the
      addition of thymidine did not prevent the enzyme inhibition. The conclusions from
      these data are that either zidovudine or zidovudine monophosphate interact
      directly with the pure enzyme, causing inhibition, while in intact cells exposed
      to the drug, zidovudine monophosphate appears to be the main metabolite
      responsible for protein kinase C inhibition.

PMID- 17040219
TI  - Protection of azidothymidine-induced cardiopathology in mice by mildronate, a
      mitochondria-targeted drug.
AB  - Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is
      a commonly used antiretroviral drug in AIDS treatment, however its use is limited
      by severe toxic side effects due to its influence on mitochondria that result in
      myopathy, particularly affecting the cardiac muscle. We suggest that effective
      protection of azidothymidine-induced cardiopathology can be expected from drugs
      that are capable of targeting mitochondria. Therefore the present study in mice
      was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine
      class, which previously has been shown to act as a highly potent protector of
      mitochondrial processes. In our study, saline (control), azidothymidine (50
      mg/kg), mildronate (50, 100 and 200 mg/kg), and azidothymidine + mildronate (at
      the doses mentioned) were injected intraperitoneally daily in separate groups of
      mice for two weeks. At the termination of the experiment, mice were sacrificed,
      the hearts were removed and cardiac tissue was examined morphologically and
      immunohistochemically. It was found that azidothymidine, compared to control and
      mildronate groups, induced major morphologic changes in cardiac tissue, which
      were manifestated as degeneration and inflammation. These changes were prevented
      when mildronate was co-administered with azidothymidine. Mildronate also reduced
      the azidothymidine-induced expression of nuclear factor kappaBp65 (NF-kappaBp65).
      The obtained data demonstrate a high ability of mildronate of preventing
      azidothymidine-induced cardiopathologic changes, and suggest mildronate's
      indirect action on azidothymidine-caused oxidative stress reactions leading to
      mitochondrial dysfunction. This offers a rational combination of mildronate with
      azidothymidine or other anti-HIV drugs for beneficial application in AIDS
      therapy.

PMID- 17040220
TI  - Evaluation of novel fluorogenic substrates for the detection of glycosidases in
      Escherichia coli and enterococci.
AB  - AIMS: Enzyme substrates based on 4-methylumbelliferone are widely used for the
      detection of Escherichia coli and enterococci in water, by detection of beta
      glucuronidase and beta-glucosidase activity respectively. This study aimed to
      synthesize and evaluate novel umbelliferone-based substrates with improved
      sensitivity for these two enzymes. METHODS AND RESULTS: A novel beta-glucuronide
      derivative based on 6-chloro-4-methylumbelliferone (CMUG) was synthesized and
      compared with 4-methylumbelliferyl-beta-D-glucuronide (MUG) using 42 strains of
      E. coli in a modified membrane lauryl sulfate broth. Over 7 h of incubation, the
      fluorescence generated from the hydrolysis of CMUG by E. coli was over twice that
      from MUG, and all of the 38 glucuronidase-positive strains generated a higher
      fluorescence with CMUG compared with MUG. Neither substrate caused inhibition of
      bacterial growth in any of the tested strains. Four beta-glucosidase substrates
      were also synthesized and evaluated in comparison with 4-methylumbelliferyl-beta
      D-glucoside (MU-GLU) using 42 strains of enterococci in glucose azide broth. The
      four substrates comprised beta-glucoside derivatives of umbelliferone-3
      carboxylic acid and its methyl, ethyl and benzyl esters. Glucosides of the
      methyl, ethyl and benzyl esters of umbelliferone-3-carboxylic acid, were found to
      be superior to MU-GLU for the detection of enterococci, especially after 18 h of
      incubation, while umbelliferone-3-carboxylic acid-beta-D-glucoside was inferior.
      However, the variability in detectable beta-glucosidase activity among the
      different strains of enterococci in short-term assays using the three carboxylate
      esters (7 h incubation) may compromise their use for rapid detection and
      enumeration of these faecal indicator bacteria. CONCLUSIONS: The beta
      glucuronidase substrate CMUG appears to be a more promising detection system than
      the various beta-glucosidase substrates tested. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The novel substrate CMUG showed enhanced sensitivity for the detection of
      beta-glucuronidase-producing bacteria such as E. coli, with a clear potential for
      application in rapid assays for the detection of this indicator organism in
      natural water and other environmental samples.

PMID- 17040221
TI  - Isolation and characterization of a bacterial strain of the genus Ochrobactrum
      with methyl parathion mineralizing activity.
AB  - AIMS: To isolate and characterize a methyl parathion (MP)-mineralizing bacterium,
      and to elucidate the degradative pathway of MP and localize the responsible
      degrading genes. METHODS AND RESULTS: A bacterial strain, designated B2, capable
      of mineralizing MP was isolated from the MP-polluted soil. Analysis of the 16S
      rRNA gene sequence and phenotypic analysis suggested that strain B2 had a close
      relationship with Ochrobactrum anthropi. B2 could totally degrade MP and four
      metabolites [p-nitrophenol (PNP), 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT)
      and hydroquinone (HQ)] were identified by HPLC and gas chromatography-mass
      spectrometry analyses. Plasmid curing of strain B2 resulted in the loss of
      ability of B2 to degrade PNP, but not the ability to hydrolyse MP. CONCLUSIONS:
      Ochrobactrum sp. B2 can mineralize MP rapidly via PNP, 4-NC, BT and HQ pathway.
      B2 harbours a plasmid encoding the ability to degrade PNP, while MP-hydrolysing
      activity is encoded on the bacterial chromosome. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This new bacterial strain (B2) capable of mineralizing MP will be useful
      in a pure-culture remediation process of organophosphate pesticides and their
      metabolites such as nitroaromatics.

PMID- 17040222
TI  - Assessment of DNA damage and repair in Mycobacterium terrae after exposure to UV
      irradiation.
AB  - AIM: Ultraviolet (UV) irradiation for drinking water treatment was examined for
      inactivation and subsequent dark and photo-repair of Mycobacterium terrae.
      METHODS AND RESULTS: UV sources tested were low pressure (monochromatic, 254 nm)
      and medium pressure (polychromatic UV output) Hg lamps. UV exposure resulted in
      inactivation, and was followed by dark or photo-repair experiments. Inactivation
      and repair were quantified utilizing a molecular-based endonuclease sensitive
      site (ESS) assay and conventional colony forming unit (CFU) viability assay.
      Mycobacterium terrae was more resistant to UV disinfection compared to many other
      bacteria, with approximately 2-log reduction at a UV fluence of 10 mJ cm(-2) ;
      similar to UV inactivation of M. tuberculosis. There was no difference in
      inactivation between monochromatic or polychromatic UV lamps. Mycobacterium
      terrae did not undergo detectable dark repair. Photo-repair resulted in recovery
      from inactivation by approximately 0.5-log in less than 30 min for both UV lamp
      systems. CONCLUSIONS: Mycobacterium terrae is able to photo-repair DNA damage
      within a short timeframe. The number of pyrimidine dimers induced by UV light
      were similar for Escherichia coli and M. terrae, however, this similarity did not
      hold true for viability results. SIGNIFICANCE AND IMPACT OF THE STUDY: There is
      no practical difference between UV sources for disinfection or prevention of DNA
      repair for M. terrae. The capability of M. terrae to photo-repair UV damage
      fairly quickly is important for wastewater treatment applications where
      disinfected effluent is exposed to sunlight. Finally, molecular based assay
      results should be evaluated with respect to differences in the nucleic acid
      content of the test micro-organism.

PMID- 17040223
TI  - Optimum melanin production using recombinant Escherichia coli.
AB  - AIMS: A parametric study was conducted to define optimum conditions to achieve
      high yields in the conversion of tyrosine to eumelanin (EuMel) using recombinant
      Escherichia coli. METHODS AND RESULTS: Escherichia coli W3110 (pTrcMutmelA)
      expressing the tyrosinase coding gene from Rhizobium etli and glucose-mineral
      media were used to transform tyrosine into EuMel. Batch aerobic fermentor
      cultures were performed to study the effect of temperature, pH and inducer
      concentration (isopropyl-D-thio-galactopyranoside) on melanin production. Under
      optimum conditions, 0.1 mmol l(-1) of isopropyl-D-thio-galactopyranoside,
      temperature of 30 degrees C, and changing pH from 7.0 to 7.5 during the
      production phase, a 100% conversion of tyrosine into EuMel is obtained.
      Furthermore, tyrosine feeding allowed us to obtain the highest level (6 g l(-1))
      of EuMel produced by recombinant E. coli reported until now. CONCLUSIONS: The
      most important factors affecting melanin formation and hence influencing the rate
      and efficiency in the conversion of tyrosine into EuMel in this system, are the
      temperature and pH. SIGNIFICANCE AND IMPACT OF THE STUDY: Maximum theoretical
      yield was obtained using a simple culture process and mineral media to convert
      tyrosine (a medium value compound) into melanin, a high value compound. The
      process reported here avoids the use of purified tyrosinase, expensive chemical
      methods or the cumbersome extraction of this polymer from animal or plant
      tissues.

PMID- 17040224
TI  - Introduction of air in the anaerobic culture of Streptococcus pneumoniae serotype
      23F induces the release of capsular polysaccharide from bacterial surface into
      the cultivation medium.
AB  - AIM: An approach to increase Streptococcus pneumoniae capsular polysaccharide
      (CPS) in the culture medium during fed-batch cultivation in bioreactor. METHODS
      AND RESULTS: Streptococcus pneumoniae serotype 23F was cultivated in a 5-l
      bioreactor with nitrogen-sparging and followed by addition of air in the
      stationary phase. The amount of CPS released in the supernatant progressively
      increased under air sparging. The profile of cellular viability and optical
      density was similar in both cultures. Immunoelectron microscopy showed that the
      amount of tightly cell-bound CPS was higher in bacteria cultivated under nitrogen
      than under air. CONCLUSIONS: The stress caused by the addition of air at the
      stationary phase promoted a large increase of free CPS into the medium, as a
      consequence of the morphologic change in the capsule. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The use of air in the stationary phase of the culture would greatly
      simplify the subsequent downstream process, allowing CPS purification from the
      supernatant. The direct consequence of this process improvement is the reduction
      of vaccine production costs.

PMID- 17040225
TI  - F+ RNA coliphage typing for microbial source tracking in surface waters.
AB  - AIMS: The utility of coliphages to detect and track faecal pollution was
      evaluated using South Carolina surface waters that exceeded State faecal coliform
      standards. METHODS AND RESULTS: Coliphages were isolated from 117 surface water
      samples by single agar layer (SAL) and enrichment presence/absence (EP/A)
      methods. Confirmed F+ RNA coliphages were typed for microbial source tracking
      using a library-independent approach. Concentrations of somatic coliphages using
      37 and 44.5 degrees C incubation temperatures were found to be significantly
      different and the higher temperature may be more specific for faecal
      contamination. The EP/A technique detected coliphages infecting Escherichia coli
      Famp in 38 (66%) of the 58 surface water samples negative for F+ coliphages by
      the SAL method. However, coliphages isolated by EP/A were found to be less
      representative of coliphage diversity within a sample. Among the 2939 coliphage
      isolates tested from surface water and known source samples, 813 (28%) were found
      to be F+ RNA. The majority (94%) of surface water F+ RNA coliphage isolates typed
      as group I. Group II and/or III viruses were identified from 14 surface water
      stations, the majority of which were downstream of wastewater discharges. These
      sites were likely contaminated by human-source faecal pollution. CONCLUSIONS: The
      results suggest that faecal contamination in surface waters can be detected and
      source identifications aided by coliphage analyses. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study supports the premise that coliphage typing can provide
      useful, but not absolute, information to distinguish human from animal sources of
      faecal pollution. Furthermore, the comparison of coliphage isolation methods
      detailed in this study should provide valuable information to those wishing to
      incorporate coliphage detection into water quality assessments.

PMID- 17040226
TI  - Genetic variability of Campylobacter jejuni isolated from fresh and frozen
      broiler carcasses.
AB  - AIMS: The aim of this study was to determine the genetic variability of
      Campylobacter jejuni isolates from poultry before and after freezing treatment in
      order to identify genotypes that would survive the treatment. METHODS AND
      RESULTS: C. jejuni was isolated from both fresh and frozen halves of the same
      carcass after freezing for 2 or more than 20 days at -20 degrees C. From 36
      carcasses, representing five unrelated flocks in Norway, a total of 209 isolates
      were included in the study. Thirty-two of the isolates were recovered with a
      qualitative method while the remaining 177 were isolated using a quantitative
      method. Isolates were genotyped with fluorescent amplified fragment length
      polymorphism using MfeI and BglII restriction enzymes. Nine different genotypes
      were identified, however, one genotype was shown to be dominant in three
      different flocks. This genotype and the dominant genotype of another flock were
      found among isolates from fresh and frozen broiler halves. They were also shown
      to be identical to genotypes frequently identified among strains isolated from
      humans, cattle and poultry flocks in previous years. CONCLUSIONS: Freezing
      treatment or isolation method appeared not to select for a particular genotype.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study indicate
      that the freezing tolerance of strains is not genotype dependent.

PMID- 17040227
TI  - Use of n-hexadecane as an oxygen vector to improve Phaffia rhodozyma growth and
      carotenoid production in shake-flask cultures.
AB  - AIMS: To identify beneficial oxygen vectors for Phaffia rhodozyma in liquid
      cultures, and to evaluate their use to improve the oxygen transfer and carotenoid
      production in the yeast cultures. METHODS AND RESULTS: Several liquid
      hydrocarbons were tested as oxygen vectors for improving the yeast growth and
      carotenoid production in shake-flask cultures of P. rhodozyma. While all nontoxic
      organic liquids (Log P: > or =5.6) showed a positive effect, n-hexadecane was
      proved to be the most beneficial for the yeast growth and carotenoid production.
      The addition of 9% (v/v) n-hexadecane to the liquid medium at the time of
      inoculation was found to be optimal, increasing the carotenoid yield by 58% (14.5
      mg l(-1) vs 9.2 g l(-1) in the control) and the oxygen transfer rate (OTR) by
      90%. CONCLUSIONS: The addition of n-hexadecane to shake-flask cultures of P.
      rhodozyma significantly improved the oxygen transfer in culture, thus increasing
      the carotenoid production. SIGNIFICANCE AND IMPACT OF THE STUDY: Use of organic
      oxygen vectors such as n-hexadecane may be a simple and useful means for
      enhancing oxygen transfer and carotenoid production in liquid fermentation of P.
      rhodozyma.

PMID- 17040228
TI  - Lipolytic activity of Antarctic cold-adapted marine bacteria (Terra Nova Bay,
      Ross Sea).
AB  - AIMS: The aim of this study was to investigate the lipolytic activity of cold
      adapted Antarctic marine bacteria and, furthermore, the combined effect of some
      environmental factors on this enzymatic process. METHODS AND RESULTS: Strains
      were assayed for lipolytic activity on a basal medium amended with seven
      individual fatty acid esters. A significant activity was observed for 148
      isolates (95.5% of the total screened). The interactive effect of pH, temperature
      and NaCl concentration on the substrates was tested for six representative
      isolates, identified as Pseudoalteromonas, Psychrobacter and Vibrio. Differences
      between strains according to NaCl and pH tolerances were observed. Only one
      strain degraded the substrate more efficiently at 4 degrees C than at 15 degrees
      C. CONCLUSIONS: Our findings demonstrate that the lipolytic activity of Antarctic
      marine bacteria is rather variable, depending on culture conditions, and occurs
      in a wide range of salt concentration and pH. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Isolation and characterization of bacteria that are able to efficiently
      remove lipids at low temperatures will provide insight into the possibility to
      use cold-adapted bacteria as a source of exploitable enzymes. Moreover, research
      on the interactive effects of salt concentration, pH and temperature will be
      useful to understand the true enzyme potentialities for industrial applications.

PMID- 17040229
TI  - Degradation of naphthenic acids by sediment micro-organisms.
AB  - AIMS: Naphthenic acids (NAs) are naturally occurring, linear and cyclic
      carboxylic surfactants associated with the acidic fraction of petroleum. NAs
      account for most of the acute aquatic toxicity of oil sands process-affected
      water (OSPW). The toxicity of OSPW can be reduced by microbial degradation. The
      aim of this research was to determine the extent of NA degradation by sediment
      microbial communities exposed to varying amounts of OSPW. METHODS AND RESULTS:
      Eleven wetlands, both natural and process-affected, and one tailings settling
      pond in Northern Alberta were studied. The natural wetlands and process-affected
      sites fell into two distinct groups based on their water chemistry. The extent of
      degradation of a 14C-labelled monocyclic NA surrogate [14C-cyclohexane carboxylic
      acid (CCA)] was relatively uniform in all sediments (approximately 30%) after 14
      days. In contrast, degradation of a bicyclic NA surrogate [14C-decahydronaphthoic
      acid (DHNA)] was significantly lower in non process-affected sediments.
      Enrichment cultures, obtained from an active tailings settling pond, using
      commercially available NAs as the sole carbon source, resulted in the isolation
      of a co-culture containing Pseudomonas putida and Pseudomonas fluorescens.
      Quantitative GC-MS analysis showed that the co-culture removed >95% of the
      commercial NAs, and partially degraded the process NAs from OSPW with a resulting
      NA profile similar to that from 'aged wetlands'. CONCLUSIONS: Exposure to NAs
      induced and/or selected micro-organisms capable of more effectively degrading
      bicyclic NAs. Native Pseudomonas spp. extensively degraded fresh, commercial NA.
      The recalcitrant NAs resembled those found in process-affected wetlands.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that it may be
      possible to manipulate the existing environmental conditions to select for a
      microbial community exhibiting higher rates of NA degradation. This will have
      significant impact on the design of artificial wetlands for water treatment.

PMID- 17040230
TI  - Glutamate dehydrogenase activity in lactobacilli and the use of glutamate
      dehydrogenase-producing adjunct Lactobacillus spp. cultures in the manufacture of
      cheddar cheese.
AB  - AIMS: The study was undertaken to investigate the occurrence of glutamate
      dehydrogenase activity in different species of lactobacilli, and to determine, in
      a series of cheese-making trials, the effects of glutamate dehydrogenase
      producing adjunct cultures on sensory attribute development during the maturation
      of cheddar cheese. METHODS AND RESULTS: The presence of dehydrogenase activity
      with glutamate as substrate was monitored in cell lysates of >100 strains from 30
      different species of lactobacilli using a qualitative colorimetric plate
      screening assay. Activity was detectable in 25 of the 29 representative species
      obtained from culture collections and in 12 of the 13 non-starter species
      isolated from cheese. There were pronounced interspecies and strain differences
      in the occurrence, level and pyridine nucleotide specificity of the glutamate
      dehydrogenase activity detected. Among the non-starter lactobacilli the highest
      frequency of enzyme occurrence and activity was detected in the Lactobacillus
      plantarum isolates. The establishment of glutamate dehydrogenase-producing
      adjunct strains in the predominant population of lactobacilli in the cheese curd
      affected the formation of a number of volatile compounds in ripening cheddar
      cheese, while the presence of Lact. plantarum strains, in particular, was
      associated with an intensification and acceleration of aroma and flavour
      development during the maturation period. CONCLUSIONS: Glutamate dehydrogenase
      formation by lactobacilli is a strain-dependent metabolic attribute, and adjunct
      cultures expressing the activity that are able to proliferate during cheese
      ripening have a positive impact on the rate of development and the intensity of
      cheddar cheese aroma and flavour development. SIGNIFICANCE AND IMPACT OF THE
      STUDY: It has been demonstrated that some strains of glutamate dehydrogenase
      producing lactobacilli have potential use as adjunct cultures to accelerate and
      intensify aroma and flavour formation during the manufacture of cheddar and, by
      analogy, other similar varieties of cheese. The importance of phenotypic
      discriminative monitoring of the dominant lactobacilli present during ripening to
      confirm adjunct establishment and population complexity was highlighted as was
      the requirement to establish the metabolic attributes of the non-starter
      population in uninoculated control cheeses in comparative trials.

PMID- 17040231
TI  - Nitrogen-fixing chemo-organotrophic bacteria isolated from cyanobacteria-deprived
      lichens and their ability to solubilize phosphate and to release amino acids and
      phytohormones.
AB  - AIMS: Cyanobacteria-deprived lichens of the species Canoparmelia caroliniana,
      Canoparmelia crozalsiana, Canoparmelia texana, Parmotrema sancti-angeli and
      Parmotrema tinctorum were screened for the presence of chemo-organotrophic
      nitrogen-fixing bacteria. METHODS AND RESULTS: Fifty-three lichen samples
      subjected to enrichment selection using a nitrogen-free minimal medium were
      positive for acetylene reduction. Seventeen isolates, able to fix nitrogen,
      belonged to Gamma-proteobacteria group and were identified as: Acinetobacter sp.,
      Pantoea sp., Pseudomonas sp., Pseudomonas stutzeri, Serratia marcescens and
      Stenotrophomonas maltophilia, according to 16S rRNA gene sequences and
      biochemical tests. The excretion of amino acid and phytohormone and the ability
      of mineral phosphate solubilization were determined in 14 isolates. All isolates
      were able to release amino acids and 3-indoleacetic acid. About 64% of the
      isolates solubilized phosphates and 30% released ethylene. CONCLUSIONS: These
      data confirm sparse evidence from the literature on the occurrence of chemo
      organotrophic nitrogen-fixing bacteria in cyanobacteria-deprived lichens; the
      isolates presented physiologic features which might benefit the host if they are
      expressed when the bacteria are harboured by lichens. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Chemo-organotrophic nitrogen-fixing bacteria were isolated from a high
      percentage (72.6%) of cyanobacteria-deprived lichens. All isolates presented
      important physiological characteristics, some of which are being described here
      for the first time.

PMID- 17040232
TI  - Interaction of Desulfovibrio desulfuricans biofilms with stainless steel surface
      and its impact on bacterial metabolism.
AB  - AIMS: To study the influence of some metallic elements of stainless steel 304 (SS
      304) on the development and activity of a sulfate-reducing bacterial biofilm,
      using as comparison a reference nonmetallic material polymethylmethacrylate
      (PMMA). METHODS AND RESULTS: Desulfovibrio desulfuricans biofilms were developed
      on SS 304 and on a reference nonmetallic material, PMMA, in a flow cell system.
      Steady-state biofilms were metabolically more active on SS 304 than on PMMA.
      Activity tests with bacteria from both biofilms at steady state also showed that
      the doubling time was lower for bacteria from SS 304 biofilms. The influence of
      chromium and nickel, elements of SS 304 composition, was also tested on a
      cellular suspension of Des. desulfuricans. Nickel decreased the bacterial
      doubling time, while chromium had no significant effect. CONCLUSIONS: The
      following mechanism is hypothesized: a Des. desulfuricans biofilm grown on a SS
      304 surface in anaerobic conditions leads to the weakening of the metal passive
      layer and to the dissolution in the bulk phase of nickel ions that have a
      positive influence on the sulfate-reducing bacteria metabolism. This phenomenon
      may enhance the biocorrosion process. SIGNIFICANCE AND IMPACT OF THE STUDY: A
      better understanding of the interactions between metallic surfaces such as
      stainless steel and bacteria commonly implied in the corrosion phenomena which is
      primordial to fight biocorrosion.

PMID- 17040233
TI  - Screening and characterization of yeasts for xylitol production.
AB  - AIMS: To discover novel naturally occurring xylitol producing yeast species with
      potential for industrial applications. METHODS AND RESULTS: Exactly 274 strains
      were cultivated on both solid and liquid screening medium with xylose as the sole
      carbon resource. Five strains were selected on the basis of significant growth
      and high degree of xylose assimilation. Their phylogenetic position was confirmed
      by the PCR-RFLP and sequence analysis of the D1/D2 domain of the 5' end of the
      large subunit rDNA gene (5'-LSU rDNA). Enzymatic analysis was conducted to
      compare xylose metabolism in each strain. Candida guilliermondii Xu280 and
      Candida maltosa Xu316 were found to have high xylose consumption rates and
      xylitol yields in the batch fermentation under micro-aerobic condition. The
      effect of the different media with high initial xylose concentration on
      biosynthesis of xylitol by both strains was investigated. CONCLUSIONS: We have
      identified Candida spp. strains, which exhibit high levels of xylitol production
      from xylose suggesting that these may have potential for industrial applications.
      SIGNIFICANCE AND IMPACTS OF THE STUDY: Microbial species are of importance for
      xylitol production. Xylitol production involves complicated metabolic regulation
      including xylose transport, production of key enzymes and cofactor regeneration.
      Thus, screening of naturally occurring xylose-utilizing micro-organisms is a
      viable and effective mean to obtain xylitol producing organisms with industrial
      application. Moreover, the research on selected strains will contribute to a
      better understanding of regulatory properties of xylose metabolism in different
      yeasts.

PMID- 17040234
TI  - Carbon : nitrogen : phosphorus ratios influence biofilm formation by Enterobacter
      cloacae and Citrobacter freundii.
AB  - AIMS: To test the effects of C : N : P ratio modification of a well-known
      nutrient medium formulation, the Endo formulation on biofilm formation by
      Enterobacter cloacae Ecl and Citrobacter freundii Cf1 in both single-species and
      binary species biofilms. METHODS AND RESULTS: The C : N : P atom : atom ratio of
      a well-known nutrient medium formulation, the Endo formulation, that has been
      applied in fermentative biohydrogen studies, was modified to include two
      different C concentrations, one containing 17.65 g l(-1) and the other 8.84 g l(
      1) sucrose, each containing four different C : N : P ratios, two at higher C : N
      : P ratios (334 : 84 : 16.8 and 334 : 84 : 3) and two at lower C : N : P ratios
      (334 : 28 : 5.6 and 334 : 28 : 1). Attached cells were enumerated after
      dislodging the biofilms that had formed on granular activated carbon (GAC). The
      modified medium containing 17.65 g l(-1) sucrose and having a C : N : P ratio of
      334 : 28 : 5.6 resulted in significantly (P < 0.05) higher counts of attached
      cells for both single-species biofilms at 7.73 log(10) CFU g(-1) GAC and 9.3
      log(10)CFU g(-1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively,
      and binary species biofilms at 8.2 log(10) CFU g(-1) GAC and 6.34 log(10) CFU g(
      1) GAC for Ent. cloacae Ecl and Cit. freundii Cf1, respectively. Scanning
      electron micrographs showed qualitative evidence that the 334 : 28 : 5.6 ratio
      encouraged more complex and extensive biofilm growth for both single-species and
      binary species biofilms. CONCLUSIONS: The differences in the attachment numbers
      between the different ratios were found not to be a result of the individual
      actions of the bacterial isolates involved but rather because of the effects of
      the various C : N : P ratios. The 334 : 28 : 5.6 ratio showed significantly (P <
      0.05) higher counts of attached cells for both single-species and binary species
      biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that C : N :
      P ratios should be a key consideration with regard to maximizing biofilm
      formation in shake flask and fluidized bed bioreactor studies as well as
      understanding fundamental factors affecting biofilm growth in natural
      environments.

PMID- 17040235
TI  - Addition of oxidizing or reducing agents to the reaction medium influences amino
      acid conversion to aroma compounds by Lactococcus lactis.
AB  - AIMS: The aim of this research was to investigate the impact of extracellular
      redox potential (Eh) on amino acid conversion to aroma compounds by Lactococcus
      lactis that is commonly used as a starter in the cheese industry. METHODS AND
      RESULTS: The study was realized in vitro by incubating resting cells of L. lactis
      in reaction media in which E(h) was modified by the addition of oxidizing or
      reducing agents. Oxidative condition (+300 mV) favoured the production of
      aldehydes and volatile sulfur compounds responsible for malty, floral, fruity,
      almond and cabbage aroma. This production was mainly the result of a chemical
      oxidation of the alpha-keto acids produced by amino acid transamination. In
      contrast, reducing condition (-200 mV) stimulated the production of carboxylic
      acids such as phenylacetic, methylthiopropionic and isovaleric acids, which
      contribute to the very-ripened-cheese aroma as well as the production of hydroxy
      acids. CONCLUSIONS: Eh of the medium highly influences the nature of aroma
      compounds produced from amino acid catabolism by the resting cells of L. lactis.
      SIGNIFICANCE AND IMPACT OF THE STUDY: E(h) is a parameter that is not controlled
      during cheese production. Its control throughout cheese making and ripening could
      permit control of aroma formation in cheese.

PMID- 17040236
TI  - Human astroviruses in raw sewage samples in Hungary.
AB  - AIMS: Routine procedures for monitoring viruses in water samples have not been
      drawn up for the water-microbiology screening panel. Enteric viruses, including
      astroviruses, are able to persist under environmental conditions and may cause
      public health problems by contaminating natural and drinking water resources. The
      aim of this study was to detect human astroviruses (HAstVs) from raw wastewater
      samples. METHODS AND RESULTS: To obtain data on whether human astroviruses are
      shed in the environment, 35 raw sewage samples from 22 sewage plants in different
      regions of Baranya County, Hungary were tested for astrovirus using a
      polyethylene glycol method for concentration and a guanidinium thiocyanate-silica
      procedure for extraction of viral RNA. Reverse transcription-polymerase chain
      reaction (RT-PCR) with HAstV-specific primer pairs was used for amplification and
      the specificity of amplicons was confirmed by nucleotide sequencing and
      phylogenetic analysis. Among the 35 raw sewage samples, 15 (43%) contained HAstV
      and by sequence analysis, 10 genotype HAstV-1 and one genotype HAstV-2 were
      identified. CONCLUSIONS: The high detection rate of astroviruses we encountered
      in this study provide convincing evidence that HAstVs circulate at a relatively
      high frequency in the Hungarian population. No correlation between the standard
      indicators of faecal pollution and the presence of HAstVs was found. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Our study is the first report on detection of HAstV in
      sewage in Hungary and suggests that HAstV might be potent indicators of viral
      pollution in environmental specimens.

PMID- 17040237
TI  - Genetic diversity and description of transmission routes for Campylobacter on
      broiler farms by amplified-fragment length polymorphism.
AB  - AIMS: To investigate the genetic diversity of Campylobacter in broilers and in
      the environment of broiler farms, to compare the genetic profiles and describe
      critical factors for transmission to broilers. METHODS AND RESULTS: Flocks at
      three of four investigated farms became colonized with Campylobacter. The total
      proportion of Campylobacter-positive samples at different farms varied from 20%
      to 42%. The farm with the poorest biosecurity routines had broilers that became
      infected earliest, the highest proportion of positive samples and the highest
      genetic diversity among the broiler Campylobacter isolates. Campylobacter
      isolates within common amplified-fragment length polymorphism (AFLP) clusters (95
      100%) were found to be present in outdoor environment and in broilers at adjacent
      farms before they were found in the broilers. A large presence of Campylobacter
      in the farm environment was demonstrated after the broilers were infected. A high
      genetic diversity was found among Campylobacter present in the outdoor
      environment, where certain Campylobacter clusters were found for periods of up to
      6 weeks. CONCLUSION: Confirmation by AFLP indicates adjacent poultry farms and
      outdoor environment as major sources of Campylobacter infection of broilers, this
      being the novel achievements. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      provide more exact knowledge on transmission of Campylobacter at farm level,
      helpful for developing optimal preventive strategies.

PMID- 17040238
TI  - Combined effect of mild heat and acetic acid treatment for inactivating
      Escherichia coli O157:H7, Listeria monocytogenes and Salmonella typhimurium in an
      asparagus puree.
AB  - AIMS: This study was conducted to validate combined heat and acid treatments for
      inactivating Escherichia coli O157:H7, Listeria monocytogenes and Salmonella
      typhimurium in an acidified brine containing, or pickled, asparagus model food.
      METHODS AND RESULTS: A mixture of three strains of E. coli O157:H7, L.
      monocytogenes and S. typhimurium were inoculated onto pickled asparagus samples.
      Combinations of various concentrations of acetic acid [0%, 0.25%, 0.5%, 0.75%,
      1%, 1.5% and 2% (v/v)] and various temperatures (40 degrees C, 50 degrees C, 60
      degrees C and 75 degrees C) were investigated. Following treatment, asparagus
      samples were stored at room temperature and enumerated at 0, 0.5, 1, 2 and 3
      days. Heat and acetic acid treatments were synergistic. The inhibitory effects of
      these combined treatments on the tested foodborne pathogens were also effective
      during storage. Loss of green colour in the pickled asparagus significantly
      increased with increasing concentrations of acetic acid. CONCLUSIONS: Using a
      combination of mild heat and acetic acid treatments can successfully control E.
      coli O157:H7, L. monocytogenes and S. typhimurium in pickled asparagus,
      combinations of heat and acid are synergistic and effective treatments can be
      selected to reduce adverse effect on colour which occur during product storage.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Mild heating plus acetic acid treatment are
      synergistic, so combined treatments can be developed, which would lower the
      temperature and amount of acetic acid required for minimally processed vegetables
      while maintaining pathogen control.

PMID- 17040239
TI  - Commensal bacilli inhibitory to mastitis pathogens isolated from the udder
      microbiota of healthy cows.
AB  - AIMS: To isolate from the microbiota of the healthy cow udder commensal bacteria
      having antimicrobial activity against bovine mastitis pathogens, with a long-term
      view to their potential application as antimastitis probiotics. METHODS AND
      RESULTS: Bacterial isolates from four healthy cow udders were tested for
      inhibitory activity against three Gram-positive indicator bacteria. This led to
      the selection of nine broadly inhibitory strains. All were of the Bacillus genus
      and their antimicrobial activities, which appeared heterogeneous on the basis of
      their antibacterial spectra and heat susceptibilities, enabled grouping of the
      inhibitory bacilli into six different inhibitory profiles. All displayed strong
      in vitro activity against Gram-positive mastitis pathogens. Inhibitory bacilli
      were recovered from each of the 11 udder samples collected over 7 months from one
      of these cows and the isolates included representatives of all six inhibitory
      profiles. CONCLUSIONS: Bacilli present in the udder microbiota of healthy cows
      can produce a variety of broadly active inhibitors of Gram-positive bacteria,
      including potential mastitis pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Inhibitor-producing strains of commensal Bacillus species have been identified,
      which may have the potential for use as possible antimastitis probiotics.

PMID- 17040240
TI  - Mechanisms of killing of spores of Bacillus subtilis by dimethyldioxirane.
AB  - AIMS: To determine the mechanisms of Bacillus subtilis spore resistance to and
      killing by a novel sporicide, dimethyldioxirane (DMDO) that was generated in situ
      from acetone and potassium peroxymonosulfate at neutral pH. METHODS AND RESULTS:
      Spores of B. subtilis were effectively killed by DMDO. Rates of killing by DMDO
      of spores lacking most DNA protective alpha/beta-type small, acid-soluble spore
      proteins (alpha- beta- spores) or the major DNA repair protein, RecA, were very
      similar to that of wild-type spore killing. Survivors of wild-type and alpha-
      beta- spores treated with DMDO also exhibited no increase in mutations. Spores
      lacking much coat protein due either to mutation or chemical decoating were much
      more sensitive to DMDO than were wild-type spores, but were more resistant than
      growing cells. Wild-type spores killed with this reagent retained their large
      pool of dipicolinic acid (DPA), and the survivors of spores treated with DMDO
      were sensitized to wet heat. The DMDO-killed spores germinated with nutrients,
      albeit more slowly than untreated spores, but germinated faster than untreated
      spores with dodecylamine. The killed spores were also germinated by very high
      pressures and by lysozyme treatment in hypertonic medium, but many of these
      spores lysed shortly after their germination, and none of these treatments were
      able to revive the DMDO-killed spores. CONCLUSIONS: DMDO is an effective reagent
      for killing B. subtilis spores. The spore coat is a major factor in spore
      resistance to DMDO, which does not kill spores by DNA damage or by inactivating
      some component needed for spore germination. Rather, this reagent appears to kill
      spores by damaging the spore's inner membrane in some fashion. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work demonstrates that DMDO is an effective
      decontaminant for spores of Bacillus species that can work under mild conditions,
      and the killed spores cannot be revived. Evidence has also been obtained on the
      mechanisms of spore resistance to and killing by this reagent.

PMID- 17040241
TI  - Degradation of mikan (Japanese mandarin orange) peel by a novel Penicillium
      species with cellulolytic and pectinolytic activity.
AB  - AIMS: The mikan, or Japanese mandarin orange, is a popular fruit in Japan, but
      its peel is one of the major agricultural wastes. The aims of this study were to
      screen, isolate, and characterize a mikan peel-degrading microbe. METHODS AND
      RESULTS: Several samples including activated sludge, sediment, compost and
      spoiled mikan peel were collected and cultured in a minimal salt medium
      containing mikan peel as the sole carbon source. Degradation activity was found
      in a culture of the spoiled mikan peel, and a fungal strain, designated OP1, with
      both cellulolytic and pectinolytic activity was isolated. No toxic metabolites,
      such as mycotoxins, were found in OP1 cultures, as evaluated by gas
      chromatography/mass spectrometry. A phylogenetic analysis strongly suggested that
      OP1 is a novel species of the genus Penicillium. CONCLUSIONS: Results suggest
      that Penicillium sp. OP1 plays an important role in aerobic microbial degradation
      of cellulose/pectin-rich biomasses in soil ecology, and further imply that this
      strain may be useful for both simultaneous cellulase/pectinase production and
      reduction of agricultural waste. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      present results advance our understanding of microbial degradation of
      cellulose/pectin-rich biomasses in the natural environment, and offer a new tool
      for reduction of agricultural waste, which is important for sustaining
      circulatory societies.

PMID- 17040242
TI  - Surface decontamination of beef inoculated with Salmonella Typhimurium DT104 or
      Escherichia coli O157:H7 using dry air in a novel heat treatment apparatus.
AB  - AIMS: To determine the effectiveness of a novel dry air decontamination apparatus
      in the deactivation of Salmonella serotype Typhimurium DT104 or Escherichia coli
      O157:H7 on beef surfaces. METHODS AND RESULTS: A laboratory scale dry air
      decontamination apparatus, capable of producing repeatable and known heating time
      temperature cycles on food surfaces was used in decontamination trials. Beef
      samples were surface inoculated with 7-8 log10CFU cm(-2) of S. Typhimurium DT104
      or E. coli O157:H7 and heated at 60, 75, 90 and 100 degrees C using fast and slow
      heating rates and subsequently held at these temperatures for up to 600 s. A
      substantial reduction in pathogen numbers was achieved at higher temperatures (90
      and 100 degrees C, 4.18-6.06 log10CFU cm(-2)) using both heating rates, but cell
      survival at these temperatures was also observed. At the lower temperatures,
      deactivation was small at 60 degrees C in particular it was less than one log
      unit after 3 min heating. No significant differences were observed when total
      reductions in pathogen counts were compared for all the temperature/heat up time
      combinations tested. During slow heating at 90 degrees C, and both heating rates
      at 100 degrees C, the pattern of deactivation of S. Typhimurium DT104 or E. coli
      O157:H7 was triphasic. CONCLUSIONS: This study has shown that heating meat
      surfaces with dry air can achieve substantial reductions in S. Typhimurium DT104
      or E. coli O157:H7. As surface decontamination of beef surfaces with dry air had
      a negative effect on beef colour and appearance, such a decontamination apparatus
      would be unsuitable for producing meat for retail sale but it could be used to
      produce safer meat for use in the catering trade. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides researchers and food processors with data on the
      dynamic changes in S. Typhimurium DT104 and E. coli O157:H7 counts on intact beef
      surfaces during heating with dry air under realistic (time-varying) temperature
      conditions.

PMID- 17040243
TI  - Campylobacter jejuni inactivation in New Zealand soils.
AB  - AIM: The study was undertaken to determine the inactivation rate of Campylobacter
      jejuni in New Zealand soils. METHODS AND RESULTS: Farm dairy effluent (FDE)
      inoculated at c. 10(5) ml(-1) with C. jejuni was applied to intact soil cores at
      a rate of 2 l m(-2). Four soils were used: Hamilton (granular); Taupo (pumice);
      Horotiu and Waihou (allophanic). After FDE application cores were incubated at 10
      degrees C for up to 32 days. For all four soils all the FDE remained within the
      cores and at least 99% of C. jejuni were retained in the top 5 cm. Campylobacter
      jejuni had declined to the limit of detection (two C. jejuni 100 g(-1)) by 25
      days in Hamilton and Taupo soils and by 32 days in Waihou soil. In contrast, in
      Horotiu soil the decline was only three orders of magnitude after 32 days.
      Simulated heavy rainfall was applied 4 and 11 days after FDE application and only
      about 1% of the applied C. jejuni were recovered in leachates. CONCLUSIONS: This
      study demonstrated that at least 99% of applied C. jejuni were retained in the
      top 5 cm of four soils where they survived for at least 25 days at 10 degrees C.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Soil retention of C. jejuni is efficient at
      FDE application rates that prevent drainage losses. The low infectious dose of C.
      jejuni and its ability to survive up to 25 days have implications for stock
      management on dairy farms.

PMID- 17040245
TI  - Zoonotic viral diseases and the frontier of early diagnosis, control and
      prevention.
AB  - Public awareness of the human health risks of zoonotic infections has grown in
      recent years. Currently, concern of H5N1 flu transmission from migratory bird
      populations has increased with foci of fatal human cases. This comes on the heels
      of other major zoonotic viral epidemics in the last decade. These include other
      acute emerging or re-emerging viral diseases such as severe acute respiratory
      syndrome (SARS), West-Nile virus, Ebola virus, monkeypox, as well as the more
      inapparent insidious slow viral and prion diseases. Virus infections with
      zoonotic potential can become serious killers once they are able to establish the
      necessary adaptations for efficient human-to-human transmission under
      circumstances sufficient to reach epidemic proportions. The monitoring and early
      diagnosis of these potential risks are overlapping frontiers of human and
      veterinary medicine. Here, current viral zoonotics and evolving threats are
      reviewed.

PMID- 17040246
TI  - Pathogenesis and treatment of diabetic vascular disease - illustrated by two
      cases.
AB  - This publication is a summary of the presentations given at the First JIM Grand
      Round held at the Sahlgrenska University Hospital on 15 March 2006. The Grand
      Round was based on two case reports; a patient with type 2 diabetes and
      pronounced macrovascular disease and another patient with early microvascular
      disease combined with the macrovascular complications. The pathogenesis of the
      vascular complications and the current treatment regimens were discussed in
      relation to the history and examinations performed in these patients.

PMID- 17040247
TI  - Right bundle branch block and long-term mortality in patients with acute
      congestive heart failure.
AB  - OBJECTIVES: Risk stratification in acute congestive heart failure (ACHF) is
      poorly defined. The aim of the present study was to assess the impact of right
      bundle brunch block (RBBB) on long-term mortality in patients presenting with
      ACHF. METHODS AND RESULTS: The initial 12-lead electrocardiogram was analysed for
      RBBB in 192 consecutive patients presenting with ACHF to the emergency
      department. The primary endpoint was all-cause mortality during 720-day follow
      up. This study included an elderly cohort (mean age 74 years) of ACHF patients.
      RBBB was present in 27 patients (14%). Age, sex, B-type natriuretic peptide
      levels and initial management were similar in patients with RBBB when compared
      with patients without RBBB. However, patients with RBBB more often had pulmonary
      comorbidity. A total of 84 patients died during follow-up. Kaplan-Meier analysis
      revealed that mortality at 720 days was significantly higher in patients with
      RBBB when compared with patients without RBBB (63% vs. 39%, P = 0.004). In Cox
      proportional hazard analysis, RBBB was associated with a two-fold increase in
      mortality (hazard ratio 2.18, 95% CI 1.26-3.66; P = 0.003). This association
      persisted after adjustment for age and comorbidity. CONCLUSIONS: RBBB is a
      powerful predictor of mortality in patients with ACHF. Early identification of
      this high-risk group may help to offer tailored treatment in order to improve
      outcome.

PMID- 17040248
TI  - Increased levels of KL-6 and subsequent mortality in patients with interstitial
      lung diseases.
AB  - OBJECTIVES: KL-6 is a specific marker in patients with interstitial lung diseases
      (ILDs); however, the relationship between elevated levels of KL-6 and subsequent
      mortality is not well defined. To determine if elevated serum levels of KL-6 are
      associated with increased mortality, and to identify the most suitable cut-off
      level of KL-6 by which to distinguish between good prognosis and poor prognosis,
      we evaluated the prognostic significance of serum KL-6 levels in patients with
      stable-state ILDs. METHODS: Two hundred and nineteen patients diagnosed with ILDs
      (152 with idiopathic interstitial pneumonia and 67 with collagen disease
      associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to
      October 2005 were entered in this study. Serum KL-6 levels in patients with ILDs
      were measured with a commercially available enzyme immunoassay kit, and these
      patients were then followed up. RESULTS: During the follow-up period, 58 of the
      219 patients died of respiratory failure. Patients who died during this period
      had higher levels of KL-6 than did those who did not (P = 0.0004). The receiver
      operating characteristic curve analysis showed 1000 U mL(-1) as the most suitable
      cut-off level by which to distinguish between the two groups of patients. The 95%
      specificity serum KL-6 level with poor outcome was 2750 U mL(-1). In univariate
      and multivariate analysis, elevated serum KL-6 (>1000 U mL(-1)) in the stable
      state indicated poor prognosis (P = 0.0005, log-rank test; P = 0.0001, Cox
      proportional hazard model). CONCLUSIONS: Elevated KL-6 level may provide simple,
      yet valuable information by which to identify patients with ILDs who are at
      increased risk for subsequent mortality.

PMID- 17040249
TI  - Characteristics and outcome amongst young adults suffering from out-of-hospital
      cardiac arrest in whom cardiopulmonary resuscitation is attempted.
AB  - OBJECTIVES: Amongst patients suffering from out-of-hospital cardiac arrest, young
      adults represent a minority. However, these victims suffer from the catastrophe
      when they are in a very active phase of life and have a long life expectancy.
      This survey aims to describe young adults in Sweden who suffer from out-of
      hospital cardiac arrest and in whom cardiopulmonary resuscitation (CPR) is
      attempted in terms of characteristics and outcome. DESIGN: Prospective and
      descriptive design. SUBJECTS AND METHODS: Young adults (18-35 years) who suffered
      from out-of-hospital cardiac arrest in whom CPR was attempted and who were
      included in the Swedish Cardiac Arrest Registry between 1990 and 2004. MAIN
      OUTCOME MEASURES: Survival to 1 month. RESULTS: In all, 1105 young adults (3.1%
      of all the patients in the registry) were included, of which 29% were females,
      51% were nonwitnessed and 15% had a cardiac aetiology. Only 17% were found in
      ventricular fibrillation, 53% received bystander CPR. The overall survival to 1
      month was 6.3%. High survival was found amongst patients found in ventricular
      fibrillation (20.8%) and those with a cardiac aetiology (14.8%). Ventricular
      fibrillation at the arrival of the rescue team remained an independent predictor
      of an increased chance of survival (odds ratio: 7.43; 95% confidence interval:
      3.44-16.65). CONCLUSION: Amongst young adults suffering from out-of-hospital
      cardiac arrest and in whom CPR was attempted, a minority survived to 1 month.
      Subgroups with a higher survival could be defined (patients found in ventricular
      fibrillation and patients in whom there was a cardiac aetiology). However, only
      one independent predictor of an increased chance of survival could be
      demonstrated, i.e. ventricular fibrillation at the arrival of the rescue team.

PMID- 17040250
TI  - Prospective study of body size and risk for stroke amongst women below age 60.
AB  - The relation between obesity, particularly abdominal obesity, and risk of stroke
      amongst women remains unclear. In 1991-1992, a prospective study was initiated in
      Sweden amongst women who returned a self-administered questionnaire. Through
      linkage with nation-wide registries, 45,449 women, free of stroke at entry, were
      followed up until diagnosis of first incident stroke, death, or the end of follow
      up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence
      intervals (CIs) from Cox proportional hazards regression models. A total of 170
      incident stroke cases occurred during an average of 11 years of follow-up. The RR
      of stroke amongst women in the highest compared with the lowest quintile was 2.4
      (95% CI 1.3-4.2; P for trend 0.04) for waist-to-hip ratio, 2.5 (95% CI 1.5-4.3; P
      for trend 0.01) for waist-to-height ratio and 2.3 (95% CI 1.2-4.3; P for trend
      0.02) for waist circumference. Adjustment for hypertension and diabetes
      attenuated these risk estimates. In contrast, birth weight, body mass index (BMI)
      at age 18, BMI at entry, weight change in adulthood and adult height were not
      significantly associated with risk of stroke. This study provides evidence that,
      in contrast to BMI, several different measures of abdominal obesity are strong
      predictors of stroke in women.

PMID- 17040251
TI  - Antipsychotics and risk of first-time hospitalization for myocardial infarction:
      a population-based case-control study.
AB  - BACKGROUND: Use of antipsychotics has been linked with an adverse cardiovascular
      risk factor profile and an increased risk of dysrhythmia and sudden cardiac
      death. However, detailed data on the association between use of antipsychotics
      and development of atherosclerotic disease are limited. OBJECTIVE: To examine
      risk of hospitalization for myocardial infarction (MI) amongst users of
      antipsychotics compared with non-users. DESIGN AND SUBJECTS: A population-based
      case-control study using data from hospital discharge registries in the counties
      of North Jutland, Viborg and Aarhus, Denmark, and the Danish Civil Registration
      System. We identified 21,377 cases of first-time hospitalization for MI and
      106,885 sex- and age-matched non-MI population controls in the period 1992-2004.
      All prescriptions for antipsychotics filled prior to the date of admission for MI
      were retrieved from population-based prescription databases. We used conditional
      logistic regression to adjust for a wide range of covariates. RESULTS: Current
      users of atypical [adjusted relative risk: 0.98, 95% confidence interval (CI):
      0.88-1.09] and typical antipsychotics (adjusted relative risk: 0.99, 95% CI: 0.96
      1.03) had no increased overall risk of being admitted to hospital for MI when
      compared with non-users of antipsychotics. These findings were consistent in all
      examined subgroups. Further, we found no association between the cumulative dose
      of antipsychotics and the risk of hospitalization for MI. CONCLUSION: These
      findings do not support the hypothesis that use of antipsychotics and in
      particular atypical antipsychotics is associated with increased risk of MI.

PMID- 17040252
TI  - A simple diagnostic strategy in hospitalized patients with clinically suspected
      pulmonary embolism.
AB  - OBJECTIVES: Diagnostic strategies in patients with suspected pulmonary embolism
      have been extensively studied in outpatients; their value in hospitalized
      patients has not been well established. Our aim was to determine the safety and
      clinical utility of a simple diagnostic strategy in hospitalized patients with
      suspected pulmonary embolism. DESIGN: Prospective management study. SETTING:
      Twelve teaching hospitals (five academic, seven general hospitals). SUBJECT: A
      total of 605 hospitalized patients with clinically suspected pulmonary embolism.
      All patients completed the study. INTERVENTIONS: First the clinical decision rule
      (CDR)-score was calculated. An unlikely CDR-score in combination with a normal D
      dimer excluded pulmonary embolism. All other patients underwent helical computed
      tomography (CT). CT either diagnosed or excluded pulmonary embolism, in which
      case anticoagulants were started or withheld. All patients were instructed to
      report symptoms of venous thrombosis. Objective tests were performed to confirm
      venous thromboembolism. The primary outcome was the incidence of symptomatic
      venous thrombosis during 3-month follow-up. RESULTS: The combination of an
      unlikely CDR-score and a normal D-dimer excluded pulmonary embolism in 60
      patients (10% of all patients); no venous thromboembolic event occurred during
      follow-up (0%; 95% CI 0-6.7%). CT excluded pulmonary embolism in 380 patients;
      during follow-up venous thromboembolism occurred in five patients (1.4%; 95% CI
      0.4-3.1%). CONCLUSIONS: An unlikely CDR-score in combination with a normal D
      dimer appears to exclude pulmonary embolism safely in hospitalized patients.
      Before clinical implementation it is important this safety is confirmed by
      others. CT testing was obviated in only 10% of patients. CT can safely exclude
      pulmonary embolism in hospitalized patients.

PMID- 17040253
TI  - The impact of gender on survival amongst patients with implantable cardioverter
      defibrillators for primary prevention against sudden cardiac death.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) are a life-saving
      therapy for many patients with cardiovascular disease at increased risk of fatal
      dysrhythmias. As men comprise the majority of the study population (67-92%) in
      clinical trials, the benefit to women is unknown. We performed a meta-analysis of
      primary prevention trials to evaluate the impact of ICDs in men and women on
      death from any cause. METHODS: Included trials met the following criteria: (i)
      randomized controlled trials versus standard of care, (ii) ICD used as primary
      prevention in a well-described protocol and (iii) data provided on risk of death
      from any cause for both male and female patients. RESULTS: Five clinical trials
      were included in this meta-analysis. The risk of death from any cause was
      significantly reduced by 26% in male patients who received ICD therapy compared
      to control, hazard ratio (HR) 0.74 (95% CI 0.60-0.91) but not amongst female
      patients, HR 0.81 (95% CI 0.60-1.09). As the COMPANION trial evaluated the
      combination of biventricular pacemaker with ICD therapy we conducted a separate
      analysis without the inclusion of this study. Male patients receiving ICD therapy
      demonstrated a similar 24% reduction in risk of death from any cause, HR 0.76
      (95% CI 0.58-0.99) whilst female patients demonstrated a reduction of only 12%,
      HR 0.88 (95% CI 0.63-1.22). CONCLUSIONS: Unlike their male counterparts, females
      did not significantly benefit from ICD therapy and without concurrent
      biventricular pacing, appear only to achieve a nonsignificant 12% reduction in
      risk of death.

PMID- 17040254
TI  - Low plasma adiponectin is associated with coronary artery disease but not with
      hypertension in high-risk nondiabetic patients.
AB  - OBJECTIVE: To investigate the association of plasma adiponectin levels with
      coronary artery disease (CAD), arterial hypertension (HT), and insulin resistance
      (IR) in nondiabetic Caucasian patients. DESIGN: We measured plasma adiponectin
      levels, IR (HOMA index), and the CAD atherosclerotic burden (angiography-based
      modified Duke Index score) in 400 nondiabetic patients undergoing coronary
      angiography. HT was diagnosed by the European Society of Hypertension/European
      Society of Cardiology (ESH/ESC) guidelines or if patients were on
      antihypertensive treatment. RESULTS: Coronary artery disease was found in 62% of
      the patients and ruled out in the rest (non-CAD group). Plasma adiponectin levels
      were inversely related to the CAD score (beta = -0.12, P = 0.029) and predicted
      the coronary atherosclerotic burden independent of other cardiovascular risk
      factors. However, they were similar in NT and HT and showed no correlation with
      blood pressure values. In non-CAD, but not in CAD patients, they were lower in
      patients with than without IR (8.3 +/- 1.2 vs. 11.3 +/- 1.3, respectively; P =
      0.007). CONCLUSIONS: In nondiabetic high-risk Caucasian patients plasma
      adiponectin levels are inversely related to CAD severity and IR; however, they
      are not strongly related to blood pressure values.

PMID- 17040256
TI  - Efficacy or effectiveness?

PMID- 17040255
TI  - HER-2 overexpression and targeted treatment by trastuzumab in a very old patient
      with gastric cancer.

PMID- 17040258
TI  - A qualitative study to assess the effectiveness of laser epilation using a
      quality-of-life scoring system.
AB  - BACKGROUND: Facial hirsutism has a negative effect on the quality of life (QOL)
      of female patients. AIM: To assess the efficacy of laser epilation on the quality
      of life in hirsute women. METHODS: Over a 6-month period, we recruited 38
      patients with severe pathological facial hirsutism. Each patient completed a
      pretreatment questionnaire consisting of a modified Dermatology Life Quality
      Index (DLQI), a visual analogue scoring system, and an 'out-of-10' scoring
      system. The patients were also scored independently by a doctor and a nurse. Each
      patient received a laser-epilation treatment programme and was reassessed in an
      identical fashion. RESULTS: Following laser epilation, the mean patient DLQI
      score fell by 5 points. All three scoring groups scored lower across all scoring
      methods following laser treatment. There was also correlation in scoring between
      disciplines. CONCLUSION: DLQI provides a valid scoring system to assess the
      efficacy of laser epilation. The interdisciplinary scores in this study indicate
      that an objective grading system for facial hirsutism could be developed in the
      future.

PMID- 17040259
TI  - Preliminary testing for normality: some statistical aspects of a common concept.
AB  - BACKGROUND: Statistical methodology has become an increasingly important topic in
      dermatological research. Adequacy of the statistical procedure depends among
      others on distributional assumptions. In dermatological articles, the choice
      between parametric and nonparametric methods is often based on preliminary
      goodness-of-fit tests. AIM: For the special case of the assumption of normally
      distributed data, the Kolmogorov-Smirnov test is the most popular choice. We
      investigated the performance of this test on four types of non-normal data,
      representing the majority of real data in dermatological research. METHODS:
      Simulations were run to assess the performance of the Kolmogorov-Smirnov test,
      depending on sample size and severity of violations of normality. RESULTS: The
      Kolmogorov-Smirnov test performs badly on data with single outliers, 10% outliers
      and skewed data at sample sizes < 100, whereas normality is rejected to an
      acceptable degree for Likert-type data. CONCLUSION: Preliminary testing for
      normality is not recommended for small-to-moderate sample sizes.

PMID- 17040261
TI  - Glomeruloid haemangioma with cerebriform morphology in a patient with POEMS
      syndrome.
AB  - A 40-year-old Chinese man presented with sensorimotor polyneuropathy, IgAlambda
      paraprotein, osteosclerotic bone lesions, hypertrichosis, and impotence with
      decreased testosterone and raised prolactin level. POEMS (polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome
      was diagnosed and he was treated with melphalan and prednisolone. After
      chemotherapy, other manifestations of POEMS syndrome developed, such as multiple
      haemangiomas over the chest and neck region, splenomegaly and generalized oedema.
      One haemangioma had a peculiar clinical morphology, similar to the appearance of
      cerebral gyri. Skin biopsy confirmed the diagnosis of glomeruloid haemangioma.
      Chemotherapy was then switched to cyclophosphamide and prednisolone, resulting in
      further improvement in muscle power and hypertrichosis. To our knowledge, this is
      the first report on a clinically distinctive morphology of glomeruloid
      haemangioma, and its recognition may increase the index of suspicion for early
      skin biopsy.

PMID- 17040260
TI  - Psychosomatic cofactors and psychiatric comorbidity in patients with chronic
      itch.
AB  - BACKGROUND: While psychosomatic factors may be involved in eliciting as well as
      coping with chronic itch, psychiatric comorbidity often goes unrecognized in
      dermatological patients. AIM: To record psychiatric illness, psychiatric and
      psychotherapeutic pretreatment, and psychotherapy indication in dermatology
      inpatients with pruritus. METHODS: A consecutive sample of 109 dermatology
      inpatients with the symptom of pruritus were examined by interviews with
      consecutive ratings by experts (using psychiatric ICD-10 diagnoses, the Global
      Assessment of Functioning Scale and the Impairment Score) and self-assessment
      using the the Eppendorf Itch Questionnaire. RESULTS: In > 70% of the pruritus
      patients, 1-6 psychiatric diagnoses could be demonstrated. In > 60%,
      psychotherapeutic or psychiatric treatment was recommended. In contrast, almost
      90% of the patients had had no previous psychotherapeutic experience. CONCLUSION:
      As psychiatric comorbidity in dermatology inpatients suffering from chronic itch
      is high, dermatology departments should aim for an improvement of their
      psychosomatic consultation and liaison services.

PMID- 17040262
TI  - Unilateral naevoid trichoepitheliomas on the face of a child.
AB  - Trichoepitheliomas are benign epidermal appendage tumours that present most
      commonly as solitary lesions, and less often as multiple, symmetrically
      distributed lesions on the face, scalp, neck and trunk. Only a few patients have
      been reported in whom trichoepitheliomas were found as unusually configured
      linear or plaque-like confluent lesions, all of which occurred in patients with
      skin types V or VI. We describe a white girl with a hemifacial plaque of
      confluent naevoid trichoepitheliomas, the first report of such lesions in a white
      patient.

PMID- 17040263
TI  - Generalized essential telangiectasia with conjunctival involvement.
AB  - Generalized essential telangiectasia (GET) is a rare skin disorder characterized
      by generalized development of dilated venules, which start at the lower
      extremities and progressively spread to the rest of the body. Mucous and
      conjunctival involvement is rare. The diagnosis is based on clinical examination,
      after excluding other primary and secondary causes of telangiectasia.

PMID- 17040264
TI  - Expression of adhesion molecules in atopic dermatitis is reduced by tacrolimus,
      but not by hydrocortisone butyrate: a randomized immunohistochemical study.
AB  - Topical tacrolimus represents an effective and well-tolerated treatment for
      atopic dermatitis (AD). Its known effects include reduced production of
      proinflammatory cytokines and reduced chemokine gradient. We performed lesional
      skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients
      were randomized to receive local treatment with tacrolimus ointment 0.1% and
      hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin
      specimen was taken. Nine patients treated with tacrolimus and seven treated with
      hydrocortisone successfully concluded the trial. By immunohistochemistry
      (alkaline phosphatase/antialkaline phosphatase method), we demonstrated that
      endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule
      (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different
      intensities and patterns of expression in untreated AD lesions. Tacrolimus
      treated specimens featured a significant reduction of the expression of ELAM-1,
      VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of
      adhesion molecule expression may represent another selective mechanism of action
      of topical tacrolimus in AD.

PMID- 17040265
TI  - Depression accompanying compensatory hyperhidrosis following endoscopic thoracic
      sympathectomy.

PMID- 17040266
TI  - Hydrous ointment: potential confusion.

PMID- 17040267
TI  - Basal cell carcinoma arising in a tattoo.

PMID- 17040268
TI  - Oropharyngeal mycosis fungoides.

PMID- 17040269
TI  - Treatment of mycosis fungoides with imiquimod 5% cream.

PMID- 17040270
TI  - Treatment of chronic erythema nodosum with infliximab.

PMID- 17040271
TI  - A case of isolated axillary hyperhidrosis successfully treated topically with 1%
      glycopyrronium cream.

PMID- 17040272
TI  - Second cite.

PMID- 17040273
TI  - Pruritic papules on the trunk of a 67-year-old man.

PMID- 17040274
TI  - An unusual tongue.

PMID- 17040275
TI  - QT interval prolongation and beyond.

PMID- 17040276
TI  - Magnitude of error introduced by application of heart rate correction formulas to
      the canine QT interval.
AB  - BACKGROUND: Accurate detection of drug-induced QT interval changes is often
      confounded by concurrent heart rate changes. Application of heart rate correction
      formulas has been the traditional approach to account for heart rate-induced QT
      interval changes, and thereby identify the direct effect of the test article on
      cardiac repolarization. Despite numerous recent studies identifying the
      imprecision of these formulas they continue to be applied. METHODS: Using a
      chronic atrioventricular dissociated His-paced canine model, heart rate
      correction methods were evaluated for their ability to generate a corrected QT
      interval independent of original heart rate. Additionally, His bundle pacing at a
      heart rate of 60 beats/min allowed calculation of the magnitude of error
      introduced by application of heart rate correction formulas. RESULTS: Of the
      fixed parameter heart rate correction formulas, only Van de Water was able to
      predict corrected QT values independent of the original heart rate. The magnitude
      of error discovered by application of heart rate correction formulas varied, but
      in many cases was very large. Bazett's formula was associated with a mean
      overcorrection of 67.9 ms; Fridericia's 28.7 ms. Van de Water was the best fixed
      parameter formula with a mean error of 10.8 ms. As expected, group and individual
      corrections derived from linear regression of the HR-QT data offered improvement
      over the traditional formulas. Both were able to predict QTc values independent
      of the heart rate. However, errors of the magnitude of 10 and 6 ms, respectively,
      were still introduced. CONCLUSION: Van de Water and linear regression correction
      methods were superior to others in this study, but all methods generated QTc
      errors equal to or much greater than the magnitude of interest for drug safety
      evaluation.

PMID- 17040277
TI  - Correlation between beat-to-beat QT interval variability and impaired left
      ventricular function in patients with previous myocardial infarction.
AB  - BACKGROUND: Beat-to-beat QT interval variability (QTV) is associated with sudden
      cardiac death and New York Heat Association functional class severity. We sought
      to evaluate the relationship between QTV and left ventricular (LV) function in
      patients with previous myocardial infarction (MI). METHODS: Fifty-nine patients
      with previous anterior MI were enrolled. LV ejection fraction (EF), LV end
      systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were
      measured by LV contrast angiography. QT interval was measured by automated
      analysis of 512-beat records of 12-lead electrocardiogram. The mean interval,
      standard deviation and variance in RR and QT intervals, and the QT variability
      index (QTVI) were calculated for each patient using two leads that corresponded
      with and without the infarction site. High-frequency power, low-frequency power,
      total-frequency power, and the ratio of low-frequency to high-frequency power in
      RR and QT intervals were calculated. RESULTS: While measured indices of RR
      intervals and indices of QT intervals, which did not correspond with the
      infarction site, did not correlate with differences in LV function, measured
      indices of QT intervals, which corresponded with the infarction site, did
      correlate with differences in LV function. However, there were no correlations
      between the ratio of low-frequency to high-frequency power in QT intervals and EF
      or LVEDVI. Correlations between QTVI and LV function were observed, particularly
      between QTVI and LVESVI (r = 0.712, P < 0.0001). CONCLUSION: In patients with
      previous anterior MI, there was variability in temporal dispersion of QT interval
      and a strong correlation between QTV corresponded with the infarcted site and LV
      function.

PMID- 17040278
TI  - Heart rate variability in young women with polycystic ovary syndrome.
AB  - BACKGROUND: Limited data are available related to the effects of sex hormones on
      cardiac autonomic function. Few studies investigated the heart rate variability
      (HRV) parameters during regular menstrual cycle or in postmenopausal women using
      hormone replacement therapy, but the results were contradictory. The aim of the
      study was to compare the characteristics of the autonomic innervation of the
      heart in polycystic ovary syndrome (PCOS) patients with regularly cycling
      controls. METHODS: Thirty PCOS patients and 30 healthy regularly cycling controls
      were included in the study. Groups were compared with respect to age and various
      cardiovascular risk factors. Characteristics of autonomic innervation of the
      heart were evaluated with HRV. Power spectral analysis of HRV was performed to
      calculate the low frequency peak (LF 0.04-0.15 Hz), high-frequency peak (HF 0.15
      0.40 Hz), LF in normalized unit (LF nu), HF in normalized unit (HF nu) and LF/HF
      ratio. RESULTS: PCOS patients had adverse cardiovascular risk profile than
      controls. As the HRV parameters, PCOS patients had significantly higher LF nu (P
      = 0.005) and LF/HF ratio (P = 0.001) and significantly lower HF (P = 0.006) and
      HF nu (P < 0.001) compared to controls. CONCLUSION: Autonomic innervation of the
      heart can be affected in PCOS with increased sympathetic and decreased
      parasympathetic components of HRV. As a result, sympathetic to parasympathetic
      ratio may increase in PCOS. This finding should be confirmed with larger studies
      also evaluating the clinical implications of altered HRV parameters.

PMID- 17040279
TI  - Uncomplicated metabolic syndrome is associated with prolonged
      electrocardiographic QTc interval and QTc dispersion.
AB  - AIM: Metabolic syndrome is associated with increased risk of mortality and
      morbidity. The present study evaluates the repolarization abnormalities in
      patients with uncomplicated metabolic syndrome measuring corrected QT interval
      (QTc) and corrected QT dispersion (QTd) on electrocardiogram. METHODS: The study
      involved 83 subjects. A total of 50 individuals met criteria of metabolic
      syndrome (Group A: 11 men, 39 women, mean body mass index (BMI) 36.7 kg/m2, mean
      waist circumference 117.3 cm). And 33 participants were healthy normal volunteers
      (Group B: 9 men, 24 women, mean BMI 21.3 kg/m2, mean waist circumference 76.2
      cm). The two groups were matched for age and sex. Metabolic syndrome was
      diagnosed according to the Adult Treatment Panel III criteria. The QTc intervals
      and QTd were measured. RESULTS: Patients with uncomplicated metabolic syndrome
      had significantly higher values of QTc-min, QTc-max, and QTd than control group
      (P < 0.001). CONCLUSION: Patients with uncomplicated metabolic syndrome have a
      greater dispersion of ventricular repolarization time and increased QTc-min and
      QTc-max.

PMID- 17040280
TI  - Reproducibility of computerized measurements of QT interval from multiple leads
      at rest and during exercise.
AB  - BACKGROUND: Accurate measurement of the QT interval is important for diagnosing
      long QT syndrome (LQTS), and in research on determinants of ventricular
      repolarization time. We tested automatic analysis of QT intervals from multiple
      ECG leads on chest. METHODS: Eleven healthy volunteers and 10 genotyped LQTS
      patients were tested at rest and during exercise with a bicycle ergometer twice 1
      31 months apart. Electrocardiograms were recorded with the body surface potential
      mapping system, and 12 precordial channels were selected for analysis. Averaged
      QT peak and QT end intervals were determined with an automated algorithm, and the
      difference QT end minus QT peak (Tp-e) was calculated. Repeatability was assessed
      by coefficient of variation (CV) between measurements. RESULTS: Within one test
      at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated
      tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected
      for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for
      QT end and 2.9% for QT peak interval. The CV of Tp-e interval was 10.2% at rest,
      and 9.3% in exercise test. Reproducibility was comparable between healthy
      subjects and LQTS patients. CONCLUSIONS: The BSPM system with automated analysis
      produced accurate and highly repeatable QT interval measurements. Reproducibility
      was adequate also over prolonged time periods both at rest and in exercise stress
      test. The method can be applied in studying duration of ventricular
      repolarization time in different physiologic and pharmacologic interventions.

PMID- 17040281
TI  - Electrocardiographic predictors of arrhythmic death.

PMID- 17040282
TI  - History of Wolff-Parkinson-White syndrome: introductory note to a classic article
      by Louis Wolff, MD, John Parkinson, MD, and Paul D White, MD.

PMID- 17040283
TI  - Bundle-branch block with short P-R interval in healthy young people prone to
      paroxysmal tachycardia. 1930.

PMID- 17040284
TI  - Wide QRS tachycardia: what is the rhythm?
AB  - We report a case of an elderly man who presented to the emergency room
      complaining of palpitations. Electrocardiogram revealed wide QRS tachycardia with
      a narrow beat within the tachycardia. Most commonly, a narrow complex beat during
      a wide complex tachycardia suggests a capture or fusion beat in the setting of
      ventricular tachycardia. However, there are situations where supraventricular
      tachycardia can also manifest this way. In our patient a pacemaker interrogation
      clarified the diagnosis.

PMID- 17040286
TI  - Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic
      markers.
AB  - Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually
      associated with previous exposure to asbestos. The incubation period of the tumor
      may be described as 30-40 years, and the prognosis is dismal. In addition to
      immunohistochemical markers, recently, serum markers for the diagnosis of
      mesothelioma have been reported as candidates. In contrast, the expression in
      renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene
      mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating
      factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It
      has also been found that N-ERC/mesothelin is very stable and plentiful in the
      blood. In the present paper the potential utility of molecular diagnostic markers
      is reviewed, including ELISA systems for asbestos-related mesothelioma.

PMID- 17040287
TI  - Immunohistochemical study of the relationship between Ki-67 labeling index of
      proliferating cells of gynecomastia, histological phase and duration of disease.
AB  - Gynecomastia is a benign proliferative lesion caused by various etiological
      factors and may result from a relative imbalance between serum estrogen and
      androgen levels. The histological alterations are similar, and gynecomastia can
      progress from a florid type to a fibrous type. The Ki-67 labeling index (LI) of
      gynecomastia specimen was investigated and higher Ki-67 LI was observed in florid
      and intermediate than in fibrous gynecomastia (P = 0.017). A correlation was
      found between the duration of disease and Ki-67 LI (P = 0.041): the shorter the
      duration the higher the Ki-67 LI. Thus, Ki-67 LI seems a useful tool to examine
      proliferation activity of gynecomastia and can assist in determination of
      appropriate treatment of gynecomastia with hormonal therapy.

PMID- 17040288
TI  - Immortalization of Epstein-Barr virus-negative human B lymphocytes with minimal
      chromosomal instability.
AB  - The genes required for immortalization of human B cells infected by Epstein-Barr
      virus are multiple, and the precise mechanism of this process remains to be
      elucidated. In the present study HPV16 E6 and E7 were retrovirally transduced
      into human primary B cells stimulated by CD40-CD40L interaction, thereby
      establishing an Epstein-Barr virus negative immortalized human B cell line, which
      continued to proliferate for more than 2 years (100 population doublings). The
      established cell line had a high telomerase activity from the beginning of the
      culture period, and no shortening of the telomere length was observed. A
      chromosomal analysis revealed that a large portion of the HPV16E6E7 transduced
      cells had retained a normal karyotype. Similar to human epithelial cells, human B
      lymphocytes seem to require two steps for immortalization, namely, the
      inactivation of the p16/Rb pathway and the activation of telomerase, the latter
      that can be induced by the CD40-CD40L interaction. Furthermore, using this
      system, it is possible to analyze the role of individual genes in human B
      lymphocyte immortalization without the influence of a pre-existing Epstein-Barr
      virus genome.

PMID- 17040289
TI  - Hepatosplenic gammadelta T-cell lymphoma following seven malaria infections.
AB  - Hepatosplenic gammadelta T-cell lymphoma (HSTL) is a clinicopathological entity
      associated with an immunocompromised status in approximately 25% of patients.
      Herein is described a case of HSTL in a 53-year-old Brazilian man with seven
      previous malaria infections, initially misdiagnosed as a hyperreactive
      splenomegaly due to chronic malaria. A characteristic lymphoid infiltrate was
      observed in spleen, liver and bone marrow sinusoids/sinuses. Neoplastic cells had
      a CD45RO+, CD2+, CD7+, CD3+, CD5-, CD8+, CD56+, perforin+, FasL-negative, T-cell
      receptor (TCR)alphabeta-negative, TCRgammadelta+ profile. Analyses of gamma and
      delta TCR rearrangements confirmed diagnosis of gammadelta T-cell lymphoma by
      detecting VgammaI/Vdelta1-Jdelta1 clonal rearrangements. Sensitive polymerase
      chain reaction (PCR) for Plasmodium falciparum, Epstein-Barr virus and
      herpesvirus-8 failed to demonstrate infection. The disease progressed to a fatal
      outcome following cutaneous infiltration and leukemic proliferation. The authors
      also comment on the association of lymphoma and infection, focusing on PCR
      diagnosis of TCRgamma and delta clonal rearrangements and the presumed pathogenic
      events leading to HSTL in the context of chronic malaria infection. Initial
      lymphomagenic stages might not be direct consequences of antigenic stimulation of
      Vdelta1 T-cells, but might depend on interactions between gammadelta T and B
      cells during cooperative or regulatory responses to Plasmodium sp.

PMID- 17040290
TI  - Sparganum mansoni parasitic infection in the lung showing a nodule.
AB  - Reported herein is a 57-year-old man infected by Sparganum mansoni, a kind of
      tapeworm, showing a solitary nodule of the middle lobe of the right lung. Because
      a transbronchial biopsy could not diagnose the nodule, a right middle lobectomy
      was performed on suspicion of malignant tumor. The lesion was diagnosed as
      sparganosis by histological and immuno-serological examinations. Histological
      examination revealed granulomatous inflammation with neutrophil and eosinophil
      infiltration around the worm and interstitial pneumonia surrounding the nodule.
      Moreover, vasculitis with foreign body giant cell was seen around the lesion. To
      the authors' knowledge this is the second case of sparganosis limited in the
      lung, and the current report presents the first detailed histological description
      of a pulmonary sparganosis case.

PMID- 17040291
TI  - Cockayne syndrome with recurrent acute tubulointerstitial nephritis.
AB  - A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was
      admitted for emaciation and dehydration. On admission the patient had mild
      chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and
      hyperuricemia. After rehydration, allopurinol was commenced for her
      hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with
      enhancement of proximal tubular dysfunction and hypertension. A renal biopsy
      showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on
      this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per
      day), following which the renal tubular function improved. However, the
      proteinuria intensified to become nephrotic syndrome. After 1 month the patient
      developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and
      renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated
      by referring to the previous reports of renal pathology in CS. It is suggested
      that rapid deterioration of the renal function in CS patients might be the result
      of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by
      ATIN, as in other reports.

PMID- 17040292
TI  - Pleomorphic lobular carcinoma in situ of the breast composed almost entirely of
      signet ring cells.
AB  - Some examples of lobular carcinoma in situ (LCIS) may be composed in part of
      signet ring cells. Such proliferations have been considered examples of
      pleomorphic LCIS based on pathological features of the more conventional
      component. However, the occurrence of LCIS composed entirely of signet ring cells
      is extraordinarily rare. This report describes an example of an in situ
      proliferation that was composed almost entirely (>95%) of signet ring cells,
      which was unassociated with an invasive carcinoma and which showed comedo-type
      necrosis. There was only focal lobulocentric distention by lesional cells, as is
      typical of classic LCIS. However, discrete, ductal-type cross-sectional profiles
      showed a purely intraepithelial proliferation of remarkably discohesive signet
      ring cells. The signet ring cells had intermediate-grade nuclear atypia, no
      significant mitotic activity and were positive for mucicarmine and PAS stains
      (the latter with and without diastase predigestion). The cells displayed marked
      immunoreactivity for high-molecular-weight keratin (stained by 34beta E12
      antibody), MUC1, gross cystic disease fluid protein-15, cytokeratin 7 and were
      negative for cytokeratin 20, E-cadherin, progesterone receptor and HER2/neu. It
      is concluded that this is an example of a purely signet ring variant of
      pleomorphic LCIS.

PMID- 17040293
TI  - Primary large cell neuroendocrine carcinoma of the urinary bladder.
AB  - Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are
      rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The
      patient was a 32-year-old man who presented with hematuria of 1 week's duration.
      On cystoscopic examination, a solitary mass measuring 3 cm in diameter was
      detected protruding from the anterosuperior wall of the urinary bladder. Two
      months after the primary transurethral resection, significant regrowth of the
      remnant mass was noted on CT, and the patient underwent a partial cystectomy. A
      diagnosis of LCNEC was made based upon histological and immunohistochemical
      findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56,
      epithelial membrane antigen, and cytokeratin. Histologically, the tumor
      penetrated the deep muscle and perivesical fat. In spite of three cycles of
      chemotherapy, the patient developed multiple metastases in the lung and liver 10
      months postoperatively. LCNEC of the urinary bladder are uncommon entities, which
      have a possible fatal outcome.

PMID- 17040294
TI  - Unusual hemangioendothelioma of the liver with epithelioid morphology associated
      with marked eosinophilia: autopsy case.
AB  - Vascular neoplasms characterized by epithelioid endothelial cells consist of
      several different entities from benignity to high-grade malignancy. Because of
      histological overlap between them, there is substantial difficulty in classifying
      them correctly. The present patient, a 33-year-old man, presented with
      hepatomegaly, striking eosinophilia and elevated serum interleukin-5 level.
      Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver,
      which is histologically distinct from epithelioid hemangioma, epithelioid
      hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had
      vasoformative and partly solid growth with no severe nuclear atypia and very low
      mitotic activity, and the histological features were similar to those of the
      entity recognized as hemangioendothelioma of bone. Organs other than the liver,
      for example the testes and bone, were also involved. This tumor should be
      considered in the differential diagnosis of severe eosinophilia.

PMID- 17040295
TI  - SMARCB1/INI1 missense mutation in mucinous carcinoma with rhabdoid features.
AB  - Malignant rhabdoid tumor (MRT) is a rare and aggressive tumor associated with
      deletion or mutation of a tumor suppressor gene SMARCB1/INI1, a member of the
      SWI/SNF chromatin-remodeling complex. Reported herein is a case of pancreatic
      mucinous carcinoma accompanying rhabdoid features with immunohistochemical and
      ultrastructural studies as well as analysis of the SMARCB1/INI1 gene. A 65-year
      old woman presented with a 2 month history of abdominal and chest pain. A well
      defined grayish tan fish-flesh mass (11 x 9 x 7 cm) with focal mucinous area was
      present in the pancreatic tail. Microscopically, the tumor had a biphasic growth
      pattern: a mucinous carcinoma component and a poorly differentiated carcinoma
      component with rhabdoid features showing loosely cohesive cells with abundant
      eosinophilic cytoplasm, displaced nuclei, and prominent nucleoli. The rhabdoid
      component coexpressed vimentin and cytokeratin. Sequencing analysis of the DNA
      extracted from the mucinous and rhabdoid components showed a missense mutation
      CCC to ACC in codon 116 of the SMARCB1/INI1 gene. Being aware of rhabdoid
      features would help diagnose this rare and aggressive malignant tumor and may
      provide an opportunity for further evaluation of SMARCB1/INI1 gene alteration and
      determination of its prognostic significance.

PMID- 17040296
TI  - Non-cystic solid-pseudopapillary tumor of the pancreas showing nuclear
      accumulation and activating gene mutation of beta-catenin.
AB  - Solid-pseudopapillary tumor (SPT) is an unusual pancreatic neoplasm that is
      characterized by a mixture of solid and cystic components and a fibrous capsule.
      Recently, the tumorigenesis of SPT has been reported to be associated with gene
      mutations of beta-catenin, which is a molecule participating in the Wnt signaling
      pathway. Reported herein is the case of a 53-year-old woman with SPT. The tumor,
      approximately 3 cm in diameter in the pancreas body, had a clear margin and
      central calcification but had neither a cystic component nor fibrous capsule.
      Several lines of pathological findings in the surgically resected specimen
      indicated SPT: (i) pseudopapillary proliferation of eosinophilic polygonal cells
      with oval nuclei; (ii) positive expression of several marker molecules indicating
      differentiation into acinar and endocrine cells; and (iii) zymogen granule-like
      structures in the cytoplasm on electron microscopy. Further, the tumor cells had
      intense nuclear accumulation of beta-catenin and an activating mutation,
      (34)Gly(GGA) to Arg(AGA), in exon 3 of the beta-catenin gene, as previously
      reported in most SPT. These findings suggest that association of the beta-catenin
      phenotype with development of the rare phenotype of SPT, a non-cystic and
      unencapsulated tumor, is unlikely.

PMID- 17040297
TI  - De novo cancers and post-transplant lymphoproliferative disorder in adult liver
      transplantation.
AB  - De novo cancer is one of the most serious complications after organ
      transplantation. Chronic immunosuppression, viral agents, pretransplant chronic
      alcohol-induced and other addictive behavior-induced injury are important
      conditions associated with the development of de novo cancers in solid organ
      transplants. The aim of the study was to evaluate types and clinical course of de
      novo cancers in adult liver transplant recipients. Data regarding 502 adult
      patients who underwent to 554 liver transplantations have been collected. Sex,
      age at transplantation, immunosuppressive regimen, time from transplantation to
      diagnosis of cancer, cancer type, surgical and non-surgical treatments and follow
      up time have been analyzed as well as acute rejection episodes and viral status.
      Thirty patients developed 31 de novo cancers. The predominant tumors were
      carcinoma of the skin, lymphomas and Kaposi's sarcoma. Kaposi's sarcoma and lung
      cancer were associated with greater mortality. In lymphomas and Kaposi's sarcoma,
      a high rate of graft involvement was observed. In liver transplant recipients, de
      novo cancers demand strategies focusing on prophylactic and careful long-term
      screening protocols. Lymphomas and Kaposi's sarcoma should be ruled out in all
      patients with clinical manifestations of chronic biliary obstruction.

PMID- 17040298
TI  - Oxygen - elixir of life or Trojan horse? Part 1: oxygen and neonatal
      resuscitation.

PMID- 17040299
TI  - Ultrasonographic guidance in pediatric regional anesthesia. Part 2: techniques.
AB  - The benefits of regional anesthesia are well documented. The downsides of such
      techniques have been a significant failure rate and a potential for serious
      complications. Nearly, all regional blocks were first described as essentially
      'blind' techniques. The development of high-resolution portable ultrasound (US)
      has made the use of US for regional anesthesia possible. Improved understanding
      of sonographic anatomy should lessen both the failure rate and the possibility of
      incurring serious complications. Natural caution has dictated that only a
      selection of blocks used in adults has been commonly used in pediatric practice,
      but with the aid of US, the repertoire of blocks for infants and children may be
      widened. The second part of this review will concentrate on the practice of both
      peripheral and central blocks.

PMID- 17040300
TI  - Outpatient arthroscopic knee surgery under combined local and intravenous
      propofol anesthesia in children and adolescents.
AB  - BACKGROUND: This prospective observational study included a case series of
      children and adolescents receiving light intravenous propofol anesthesia combined
      with local anesthesia (LA) for arthroscopic knee procedures. The aim was to
      examine the merits of anesthesia, to discuss the indications for the procedure
      and to analyze recovery/discharge times from the postanesthesia care unit (PACU).
      METHODS: A cohort of 147 children and adolescents (ASA 1 and 2) aged 12-18 years
      admitted for outpatient arthroscopic knee procedures between January 2004 and May
      2005 were studied. After IV access in the operating theater, the patients
      received propofol (10 mg.ml(-1)). Arthroscopy was performed approximately 15 min
      after injecting local anesthetic (15 ml 2% lidocaine with epinephrine 1:200,000)
      partly at the site of insertion of the arthroscope and other instruments (5 ml),
      and the rest intra-articular. The following parameters were assessed: airway
      patency, propofol requirement, vital signs, procedure time, surgical operating
      conditions, patient satisfaction score, time to discharge, postoperative
      analgesia and adverse events. RESULTS: Of 147 patients, 133 patients (90.5%)
      underwent arthroscopic knee surgery, whereas knee arthroscopy alone was performed
      in 14 patients (9.5%) without indication for operative treatment. The arthroscopy
      was well tolerated in 96.6% patients (no pain, movement or discomfort during the
      procedure) and only five patients required conversion to general anesthesia. Pain
      experienced during the injection of lidocaine was more severe than pain
      experienced during the surgical procedure itself (P < 0.001). The surgical
      evaluation of operative conditions (visualization and access to intra-articular
      structures) was generally satisfactory and completely acceptable. Almost 94%
      (138/147) of patients said they would have the same procedure again under the
      same type of anesthesia. The mean propfol induction dose was 1.4 mg.kg(-1)
      (range: 0.9-3.8) and mean propofol infusion rate 167 microg.kg(-1).min(-1)
      (range: 130-250). Movement was more likely at lower infusion rates (mean: 151
      microg.kg(-1).min(-1)). The maximal decrease in respiratory rate was 5.9 +/- 5.1
      br.min(-1) (27.2 +/- 21%) and no patient became hypoxic. Patients recovered to
      preoperative values at 9.8 +/- 7.5 min following infusion discontinuation. There
      were no respiratory or cardiovascular complications. The mean stay in PACU was 47
      min (range: 32-150). As many as 71% (105/147) of patients required no analgesics
      during the first two postoperative hours. CONCLUSIONS: The combination of light
      intravenous propofol anesthesia combined with local anesthesia for arthroscopic
      knee procedures provided effective sedation, good preservation of upper airway
      patency, rapid recovery and pain relief without major side effects and offers a
      good alternative to the methods already available. The majority of patients did
      not require postoperative analgesia.

PMID- 17040301
TI  - Esophageal saturation during antegrade cerebral perfusion: a preliminary report
      using visible light spectroscopy.
AB  - BACKGROUND: Visible light spectroscopy (VLS) is newer technology that measures
      real-time tissue oxygenation. It has been validated in detecting mucosal ischemia
      in adults. During complex neonatal heart surgery, antegrade cerebral perfusion
      (ACP) maintains cerebral saturation. Whether ACP maintains peripheral tissue
      perfusion in humans is not known. METHODS: Five patients undergoing neonatal open
      heart surgery with hypothermic cardiopulmonary bypass (CPB) were studied using a
      VLS esophageal probe in addition to bilateral near infrared cerebral oximetry.
      Three of five patients required ACP for arch repair, while two patients did not.
      VLS and cerebral saturation data were collected and analyzed in 5 min intervals
      prior to CPB, during CPB, and during ACP. RESULTS: In the two patients undergoing
      heart surgery with routine hypothermic CPB, both cerebral and esophageal
      saturations were maintained. However in all three neonates requiring ACP,
      although cerebral saturations did not decrease, esophageal saturation fell below
      the ischemic threshold (35%). Following establishment of normal CPB, esophageal
      saturation returned to baseline. CONCLUSIONS: Antegrade cerebral perfusion
      maintains cerebral oxygen delivery, however, it does not adequately perfuse the
      esophagus in neonates. This could have clinical implications.

PMID- 17040302
TI  - Emergence agitation in preschool children: double-blind, randomized, controlled
      trial comparing sevoflurane and isoflurane anesthesia.
AB  - BACKGROUND: This randomized, double-blind controlled trial was conducted to
      determine whether the association of sevoflurane for induction and isoflurane for
      anesthesia maintenance resulted in a lower incidence of postoperative agitation
      compared with sevoflurane as single agent. METHODS: After Institute Ethics
      Committee's approval and parental written informed consent, 128 unpremedicated
      children (1-6 years), ASA I-II, scheduled for elective subumbilical surgery were
      enrolled. After induction with 8% sevoflurane, patients were randomly allocated
      to receive sevoflurane or isoflurane 1-1.5 MAC as maintenance agent. The primary
      endpoint of the study was the incidence of postoperative agitation defined as a
      screaming and crying child and/or a child that required physical restraint during
      emergence. RESULTS: Eighteen children were excluded because they received
      sedatives, analgesia or anesthesia or because of ineffective regional analgesia
      before randomization. Fifty-four patients receiving sevoflurane and 56 receiving
      isoflurane completed the study. Twenty-eight children (95% CI 38-66%) in the
      sevoflurane group presented with postoperative agitation compared with 18 (95% CI
      20-46%) patients receiving isoflurane (P = 0.028). Fifteen minutes after
      awakening, 11/54 children receiving sevoflurane were agitated compared with 4/56
      receiving isoflurane (P = 0.03). Thereafter, there was a gradual reduction in the
      incidence of postoperative agitation over time. CONCLUSIONS: The association of
      sevoflurane for induction and isoflurane for maintenance produced significant
      less postoperative agitation in preschool children receiving regional anesthesia
      during subumbilical surgery compared with sevoflurane for induction and
      maintenance.

PMID- 17040303
TI  - Safe removal of LMA in children - at what BIS?
AB  - BACKGROUND: Removal of an LMA without producing untoward complications has
      remained a matter of concern to all anesthesiologists; more so in pediatric
      practice where the margin of safety is narrow. Most work on LMA in adults
      supports its removal following return of airway reflexes. The situation regarding
      its removal in children is, however, less clear. METHODS: We conducted a
      randomized, prospective study to compare incidence of airway complications after
      removal of the LMA at deep or awake planes in 120 children, ASA I or II, aged 1-8
      years and to objectively determine the most appropriate Bispectral index (BIS) to
      allow safe removal of an LMA in children. They were studied in two groups of 60
      and depth of anesthesia (whether awake-Gp A or deep-Gp D) for LMA removal was
      decided by random distribution from sealed envelopes. BIS was recorded
      continuously for all the patients until 2 min after removal of LMA. RESULTS: Mean
      SpO2 after removal of LMA was 93% Gp A and 98% in Gp D. The mean duration of
      surgery in Gp A was 53.9 +/- 10 and in Gp D 46.7 +/- 4 min. PESev at removal in
      Gp A was 0.20 +/- 0.16 and in Gp D was 0.59 +/- 0.1. BIS median in Gp A was 79
      with a maximum of 86 and minimum of 66. In Gp D BIS, median was 60 with maximum
      of 76 and minimum of 58. The number of patients with airway complications in
      awake removal group was 21 (35%) and in deep removal group was 4 (6.6%).
      CONCLUSIONS: Bispectral index scoring should prove a useful adjunct to the
      present monitoring and can be used to achieve smoother emergence conditions. We
      suggest that LMA removal should be attempted in children when a BIS value of
      approximately 60 is reached.

PMID- 17040304
TI  - Pain management in fulminating ulcerative colitis.
AB  - BACKGROUND: Toxic megacolon is a life-threatening complication of ulcerative
      colitis (UC) characterized by systemic toxicity, loss of blood per rectum and
      severe pain. Pain management is challenging in these patients because
      nonsteroidal anti-inflammatory drugs may exacerbate bleeding and opioids are
      contraindicated because they adversely affect bowel peristalsis causing an
      increased risk of colonic perforation. METHODS: We describe three episodes of
      fulminating UC in two children in whom ketamine analgesia was used. Our protocol
      for a low-dose continuous ketamine infusion with either nurse-controlled
      analgesia (NCA) or patient-controlled analgesia (PCA) bolus administration is
      presented and a review of the literature regarding the use of ketamine analgesia
      in children is discussed. RESULTS: Low-dose ketamine N/PCA with a continuous
      background infusion provided satisfactory analgesia and none of our children
      reported adverse effects. CONCLUSIONS: We have demonstrated the safe and
      effective use of ketamine analgesia in children with toxic megacolon, a condition
      in which the child is in severe pain and morphine is contraindicated.

PMID- 17040305
TI  - A factorial study of ondansetron, metoclopramide, and dexamethasone for emesis
      prophylaxis after adenotonsillectomy in children.
AB  - BACKGROUND: We conducted a factorial study of emesis prophylaxis with ondansetron
      (OND), metoclopramide (MET), and dexamethasone (DEX). METHODS: After informed
      parental consent, 240 children having adenotonsillectomy were randomized to one
      of 15 combinations of OND (0-60 microg.kg(-1)), MET (0-400 microg.kg(-1)), and/or
      DEX (0-500 microg.kg(-1)). Using multivariable logistic regression, models were
      generated for the probability of emesis before discharge, after discharge and
      overall for 24 h. RESULTS: Odds of emesis increased by a factor of three to four
      for children older than 7 years. Before discharge, odds of emesis decreased by
      factors of 0.29 for each 15 microg.kg(-1) of OND and 0.37 for each 100 microg.kg(
      1) of MET. After discharge, odds of emesis decreased by a factor of 0.67 for each
      125 microg.kg(-1) of DEX and increased by a factor of 3.5 for emesis before
      discharge. Over 24 h, odds of emesis decreased with OND, MET, and DEX (ORs as
      above). A negative interaction between OND and MET was seen before discharge and
      over 24 h, reducing the efficacy of their combination. CONCLUSIONS: We present
      novel study design and methods of analysis which are uniquely suited to studies
      of multiple interventions. Factorial design was a powerful tool, allowing
      simultaneous determination of dose-response relationships for three drugs and
      identifying a previously unreported negative interaction between OND and MET.

PMID- 17040306
TI  - Intraoperative and postoperative risk factors for prolonged mechanical
      ventilation after pediatric cardiac surgery.
AB  - BACKGROUND: Early extubation after cardiac surgery in children is feasible;
      however, predictors of prolonged mechanical ventilation (MV) should be recognized
      as soon as possible. METHODS: At a tertiary pediatric cardiac center, prospective
      case series analyses were carried out with a total of 411 patients within 1 year
      of cardiac surgery. Perioperative factors were evaluated for strength of
      association with duration of MV > 61 h (medium, MMV) and > 7 days (long, LMV).
      Two multiple regression models were performed for both cut-off points: one model
      considered factors identified until 24 h postoperation, the other was performed
      with all parameters. RESULTS: One hundred and three patients (25%) were still
      intubated after 61 h; 38 patients required LMV and they occupied 33% of total
      intensive care unit (ICU) bed days. If factors occurring until 24 h after surgery
      were analyzed, duration of cardiopulmonary bypass (CPB), intraoperative
      transfusion, post-CPB arterial oxygen tension (PaO2/FiO2), and fluid intake on
      the first day were found to be associated with MMV. Urea nitrogen value, nitric
      oxide treatment, delayed sternal closure, and tracheobronchomalacia, measured at
      the same point of time, were independent predictors of LMV. Of all the studied
      clinical predictors, MMV was associated with pulmonary hypertensive events,
      delayed sternal closure, peritoneal dialysis, nonvascular pulmonary problems, low
      output syndrome and fluid intake, while urea nitrogen (24 h), postsurgical
      neurological events, nitric oxide, tracheobronchomalacia, pulmonary hypertensive
      events and cardiac reoperations were identified as determinants of LMV.
      CONCLUSIONS: Causes of MV after surgery are heterogeneous, vary with time, and
      have variable impact on the duration of MV.

PMID- 17040307
TI  - Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine
      overdose in a pediatric patient.
AB  - Carbamazepine (CBZ) intoxication is an important issue in acute poisoning
      practice. Highly protein-bound, CBZ is not removed efficiently through
      conventional hemodialysis. We describe the use of continuous venovenous
      hemodiafiltration (CVVHDF) in a 2-year-old boy who developed general tonic clonic
      seizure and respiratory depression due to controlled-release formula of CBZ
      overdose (peak drug level of > 20 microg.ml(-1), therapeutic range: 5-10
      microg.ml(-1)). Serum CBZ concentrations fell to 0.25 microg.ml(-1) at the end of
      hemodiafiltration. The patient recovered rapidly and was discharged from hospital
      4 days from the time of ingestion with no complications or neurologic impairment.

PMID- 17040308
TI  - Cardiac arrest at induction of anesthesia in a child with undiagnosed right
      ventricular dependent coronary circulation: a case report.
AB  - Pediatric perioperative cardiac arrest occurs in 1.4 per 10,000 anesthetics, with
      an overall mortality rate of 26%. The etiology of the arrest is identifiable in
      the majority of these patients. We report the case of a child with a complex
      congenital heart defect, who sustained a cardiac arrest at induction of
      anesthesia, secondary to right-ventricular dependent coronary circulation. We
      discuss the incidence, risks, anesthetic management and outcomes of pediatric
      cardiac arrest in the perioperative period especially in patients with complex
      congenital heart disease.

PMID- 17040309
TI  - Anesthesia management with short acting agents for bilateral pheochromocytoma
      removal in a 12-year-old boy.
AB  - A 12-year-old boy with bilateral adrenal pheochromocytoma pretreated with
      furosemide, nifedipine, prazosin, and propranolol underwent surgical removal of
      the tumors. General anesthesia with desflurane, remifentanil infusion and
      thoracic epidural analgesia was performed. To control the blood pressure (BP),
      remifentanil up to 1 microg.kg(-1).min(-1) infusion rate, sodium nitroprusside,
      and esmolol infusions were administered successfully. Following the ligation of
      the adrenal veins, hemodynamic parameters were stable and neither inotropic
      support nor corticosteroid replacement was required. We concluded that
      remifentanil-based anesthesia combined with low-dose desflurane and thoracic
      epidural analgesia may reduce the need for vasoactive drugs in the anesthesia
      management of pheochromocytoma. This combination may not prevent the hemodynamic
      fluctuations during tumor manipulation, but appears to facilitate a rapid and
      stable postoperative recovery.

PMID- 17040310
TI  - Anesthesia management for the child with Sanjad-Sakati syndrome.
AB  - Sanjad-Sakati syndrome (SSS) is a rare genetic disorder characterized by
      congenital hypoparathyroidism, hypocalcemia and hyperphosphatemia, seizures,
      severe intrauterine and postnatal growth failure, dwarfism, mental retardation,
      dysmorphic features including retromicrognathia and abnormal dentition and
      increased susceptibility to infection. It is mainly confined to children in the
      Middle-East countries. We report the anesthesia management of a 12-year-old boy
      with SSS for dental treatment, and discuss the anesthesia implications of this
      disorder.

PMID- 17040311
TI  - Therapeutic airway obstruction.

PMID- 17040312
TI  - Intraoperative cardiac arrest because of oculocardiac reflex and subsequent
      pulmonary edema in a patient with extraocular cysticercosis.

PMID- 17040313
TI  - Anesthetic management of a patient with Moyamoya disease undergoing open heart
      surgery.

PMID- 17040314
TI  - To make epidural catheterization less difficult in infants.

PMID- 17040315
TI  - Caudal anesthesia in children with shunt devices.

PMID- 17040316
TI  - Torsades de pointes with sevoflurane.

PMID- 17040318
TI  - Inadvertent bolus administration of high-dose remifentanil during anesthesia in a
      6-year-old girl.

PMID- 17040319
TI  - Predation on mutualists can reduce the strength of trophic cascades.
AB  - Ecologists have put forth several mechanisms to predict the strength of predator
      effects on producers (a trophic cascade). We suggest a novel mechanism--in
      systems in which mutualists of plants are present and important, predators can
      have indirect negative effects on producers through their consumption of
      mutualists. The strength of predator effects on producers will depend on their
      relative consumption of mutualists and antagonists, and on the relative
      importance of each to producer population dynamics. In a meta-analysis of
      experiments that examine the effects of predator reduction on the pollination and
      reproductive success of plants, we found that the indirect negative effects of
      predators on plants are quite strong. Most predator removal experiments measure
      the strength of predator effects on producers through the antagonist pathway; we
      suggest that a more complete understanding of the role of predators will be
      achieved by simultaneously considering the effects of predators on plant
      mutualists.

PMID- 17040320
TI  - The silver spoon effect and habitat selection by natal dispersers.
AB  - The silver spoon effect in the context of habitat selection occurs when
      dispersers in good condition are more likely to settle in high-quality habitats
      than dispersers in poor condition. Positive relationships between disperser
      condition and the quality of post-dispersal habitats are predicted by at least
      two non-exclusive ultimate hypotheses. The competition hypothesis assumes that a
      disperser's condition affects its chances of competing for space or joining an
      established group after arriving at a high-quality habitat, while the search
      hypothesis assumes that a disperser's condition affects its selectivity, and
      hence its chances of accepting a lower-quality habitat when it is searching for a
      new habitat. Thus far, silver spoon effects in the context of habitat selection
      have been reported in only a handful of species (several birds and marine
      invertebrates), but this study suggests that they may be relatively common in
      particular species and situations.

PMID- 17040321
TI  - Stoichiometry of consumer-driven nutrient recycling across nutrient regimes in
      streams.
AB  - Stoichiometric constraints within ecological interactions and their ecosystem
      consequences may depend on characteristics of the abiotic environment such as
      background nutrient levels. We assessed whether consumer identity, via differing
      body stoichiometry, could regulate periphyton stoichiometry across nutrient
      regimes in open systems. In 60 flow-through artificial streams, we factorially
      crossed dissolved inorganic nitrogen levels (elevated = 294 micog L(-1), ambient
      = 26 microg L(-1)) with dissolved inorganic phosphorus levels (DIP: elevated = 15
      microg L(-1), ambient = 3 microg L(-1)) and consumer type [crayfish (body N : P =
      18), snails (body N : P = 28) or a control]. At ambient DIP, periphyton in the
      crayfish treatment had a lower %P and a lower C : P than periphyton in the snail
      treatment suggesting that consumer identity, probably mediated by differing P
      excretion, regulated periphyton P content. At high DIP, consumer identity no
      longer affected periphyton elemental composition. Therefore, the stoichiometry of
      consumer-driven nutrient recycling and consumer identity may be less important to
      ecosystem functioning in environments with elevated nutrient levels.

PMID- 17040322
TI  - Weed evolution after crop gene introgression: greater survival and fecundity of
      hybrids in a new environment.
AB  - Crop-wild hybridization may produce offspring with lower fitness than their wild
      parents due to deleterious crop traits and outbreeding depression. Over time,
      however, selection for improved fitness could lead to greater invasiveness of
      hybrid taxa. To examine evolutionary change in crop-wild hybrids, we established
      four wild (Raphanus raphanistrum) and four hybrid radish populations (R.
      raphanistrum x Raphanus sativus) in Michigan (MI), USA. Hybrid and wild
      populations had similar growth rates over four generations, and pollen fertility
      of hybrids improved. We then measured hybrid and wild fitness components in two
      common garden sites within the geographical range of wild radish [MI and
      California (CA)]. Advanced generation hybrids had slightly lower lifetime
      fecundity than wild plants in MI but exhibited c. 270% greater lifetime fecundity
      and c. 22% greater survival than wild plants in CA. Our results support the
      hypothesis that crop-wild hybridization may create genotypes with the potential
      to displace parental taxa in new environments.

PMID- 17040323
TI  - Invariant scaling of phytoplankton abundance and cell size in contrasting marine
      environments.
AB  - Scaling relationships such as the variation of population abundance with body
      size provide links between individual organisms and ecosystem functioning.
      Previous work, in marine pelagic ecosystems, has focused on the relationship
      between total phytoplankton abundance and the assemblage mean cell size. However,
      the relationship between specific population abundance and cell size in marine
      phytoplankton has received little attention. Here, we show that cell size
      accounts for a significant amount of variability in the population abundance of
      phytoplankton species across a cell volume range spanning seven orders of
      magnitude. The interspecific scaling of population abundance and cell size takes
      a power exponent near -3/4. Unexpectedly, despite the constraints imposed on
      large phytoplankton by limited resource acquisition, the size scaling exponent
      does not differ between contrasting marine environments such as coastal and
      subtropical regions. These findings highlight the adaptive abilities of
      individual species to cope with different environmental conditions and suggest
      that a general rule such as the 'energetic equivalence' constrains the abundance
      of phytoplankton populations in marine pelagic ecosystems.

PMID- 17040324
TI  - Structure of Caribbean coral reef communities across a large gradient of fish
      biomass.
AB  - The collapse of Caribbean coral reefs has been attributed in part to historic
      overfishing, but whether fish assemblages can recover and how such recovery might
      affect the benthic reef community has not been tested across appropriate scales.
      We surveyed the biomass of reef communities across a range in fish abundance from
      14 to 593 g m(-2), a gradient exceeding that of any previously reported for coral
      reefs. Increased fish biomass was correlated with an increased proportion of apex
      predators, which were abundant only inside large marine reserves. Increased
      herbivorous fish biomass was correlated with a decrease in fleshy algal biomass
      but corals have not yet recovered.

PMID- 17040325
TI  - Allometric scaling enhances stability in complex food webs.
AB  - Classic local stability theory predicts that complex ecological networks are
      unstable and are unlikely to persist despite empiricists' abundant documentation
      of such complexity in nature. This contradiction has puzzled biologists for
      decades. While some have explored how stability may be achieved in small modules
      of a few interacting species, rigorous demonstrations of how large complex and
      ecologically realistic networks dynamically persist remain scarce and
      inadequately understood. Here, we help fill this void by combining structural
      models of complex food webs with nonlinear bioenergetic models of population
      dynamics parameterized by biological rates that are allometrically scaled to
      populations' average body masses. Increasing predator-prey body mass ratios
      increase population persistence up to a saturation level that is reached by
      invertebrate and ectotherm vertebrate predators when being 10 or 100 times larger
      than their prey respectively. These values are corroborated by empirical predator
      prey body mass ratios from a global data base. Moreover, negative effects of
      diversity (i.e. species richness) on stability (i.e. population persistence)
      become neutral or positive relationships at these empirical ratios. These results
      demonstrate that the predator-prey body mass ratios found in nature may be key to
      enabling persistence of populations in complex food webs and stabilizing the
      diversity of natural ecosystems.

PMID- 17040326
TI  - Spatial segregation of specialists and generalists in bird communities.
AB  - Each species generally has a close relationship with one or more habitats and can
      therefore be classified as either specialist or generalist. We studied whether
      specialist and generalist species are spatially distributed independently of each
      other. Repeating the analysis for 100 of the most frequent terrestrial bird
      species recorded over the 10 000 sampled sites of the French Breeding Bird
      survey, we found that specialists were more abundant if the rest of the community
      was specialized, and that the inverse was also true. This pattern was far subtler
      than just a simple dichotomy: most species actually presented a maximum abundance
      at a value of community specialization similar to their own level of
      specialization. Bird communities appear very well defined along a specialist
      generalist gradient. We believe this pattern becomes more apparent with habitat
      degradation. The consequences on both ecological services and community
      resilience may well be considerable.

PMID- 17040327
TI  - Habitat effects on the relative importance of trait- and density-mediated
      indirect interactions.
AB  - Classical views of trophic cascades emphasize the primacy of consumptive predator
      effects on prey populations to the transmission of indirect effects [density
      mediated indirect interactions (DMIIs)]. However, trophic cascades can also
      emerge without changes in the density of interacting species because of non
      consumptive predator effects on prey traits such as foraging behaviour [trait
      mediated indirect interactions (TMIIs)]. Although ecologists appreciate this
      point, measurements of the relative importance of each indirect predator effect
      are rare. Experiments with a three-level, rocky shore food chain containing an
      invasive predatory crab (Carcinus maenas), an intermediate consumer (the snail,
      Nucella lapillus) and a basal resource (the barnacle, Semibalanus balanoides)
      revealed that the strength of TMIIs is comparable with, or exceeds, that of
      DMIIs. Moreover, the sign and strength of each indirect predator effect depends
      on whether it is measured in risky or refuge habitats. Because habitat shifts are
      often responsible for the emergence of TMIIs, attention to the sign and strength
      of these interactions in both habitats will improve our understanding of the link
      between individual behaviour and community dynamics.

PMID- 17040328
TI  - How parasites affect interactions between competitors and predators.
AB  - We present a synthesis of empirical and theoretical work investigating how
      parasites influence competitive and predatory interactions between other species.
      We examine the direct and indirect effects of parasitism and discuss examples of
      density and parasite-induced trait-mediated effects. Recent work reveals
      previously unrecognized complexity in parasite-mediated interactions. In addition
      to parasite-modified and apparent competition leading to species exclusion or
      enabling coexistence, parasites and predators interact in different ways to
      regulate or destablize the population dynamics of their joint prey. An emerging
      area is the impact of parasites on intraguild predation (IGP). Parasites can
      increase vulnerability of infected individuals to cannibalism or predation
      resulting in reversed species dominance in IGP hierarchies. We discuss the
      potential significance of parasites for community structure and biodiversity, in
      particular their role in promoting species exclusion or coexistence and the
      impact of emerging diseases. Ongoing invasions provide examples where parasites
      mediate native/invader interactions and play a key role in determining the
      outcome of invasions. We highlight the need for more quantitative data to assess
      the impact of parasites on communities, and the combination of theoretical and
      empirical studies to examine how the effects of parasitism scale up to community
      level processes.

PMID- 17040330
TI  - Psychiatric comorbidity of migraine.
AB  - Migraine affects nearly 12% of the adult population in the United States and
      causes significant lost productivity and decrements in health-related quality of
      life. The burden of migraine and the challenge in managing it are increased by
      the comorbid psychiatric conditions that occur in association with it. Studies in
      both clinical and community-based settings have demonstrated an association
      between migraine and a number of specific psychiatric disorders. This review will
      focus on the relationships between migraine and depression, generalized anxiety
      disorder, panic disorder, and bipolar disorder. In large scale population-based
      studies, persons with migraine are from 2.2 to 4.0 times more likely to have
      depression. In longitudinal studies, the evidence supports a bidirectional
      relationship between migraine and depression, with each disorder increasing the
      risk of the other disorder. Migraine is also comorbid with generalized anxiety
      disorder (Odds Ratio [OR] 3.5 to 5.3), panic disorder (OR 3.7), and bipolar
      disorder (OR 2.9 to 7.3). A diagnosis of migraine should lead to a heightened
      level of diagnostic suspicion for these comorbid psychiatric disorders.
      Similarly, a diagnosis of one of these psychiatric disorders should increase
      vigilance for migraine. Treatment plans for migraine should be mindful of the
      comorbid conditions.

PMID- 17040331
TI  - Modifiable risk factors for migraine progression.
AB  - Migraine is a chronic-recurrent disorder that progresses in some individuals.
      Transformed migraine is the result of this progression. Since migraine does not
      progress in most patients, identifying the risk factors for progression has
      emerged as a very important public health priority. If risk factors can be
      identified, that might provide a foundation for more aggressive preventive
      intervention. Risk factors for progression may be divided into non-remediable
      (gender, age, race) and remediable categories. In this paper, we focus on several
      already identified remediable risk factors, including frequency of migraine
      attacks, obesity, acute medication overuse, caffeine overuse, stressful life
      events, depression, and sleep disorders. We present the evidence for each risk
      factor and discuss possible interventions to address them.

PMID- 17040332
TI  - Headache and sleep disorders: review and clinical implications for headache
      management.
AB  - Review of epidemiological and clinical studies suggests that sleep disorders are
      disproportionately observed in specific headache diagnoses (eg, migraine, tension
      type, cluster) and other nonspecific headache patterns (ie, chronic daily
      headache, "awakening" or morning headache). Interestingly, the sleep disorders
      associated with headache are of varied types, including obstructive sleep apnea
      (OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and
      hypersomnia. Headache, particularly morning headache and chronic headache, may be
      consequent to, or aggravated by, a sleep disorder, and management of the sleep
      disorder may improve or resolve the headache. Sleep-disordered breathing is the
      best example of this relationship. Insomnia is the sleep disorder most often
      cited by clinical headache populations. Depression and anxiety are comorbid with
      both headache and sleep disorders (especially insomnia) and consideration of the
      full headache-sleep-affective symptom constellation may yield opportunities to
      maximize treatment. This paper reviews the comorbidity of headache and sleep
      disorders (including coexisting psychiatric symptoms where available). Clinical
      implications for headache evaluation are presented. Sleep screening strategies
      conducive to headache practice are described. Consideration of the spectrum of
      sleep-disordered breathing is encouraged in the headache population, including
      awareness of potential upper airway resistance syndrome in headache patients
      lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep
      regulation strategies are offered that are also compatible with treatment of
      primary headache.

PMID- 17040333
TI  - The neuropsychology of recurrent headache.
AB  - Headache is recognized as one of the most prevalent neurological disorders, and
      is the most frequently reported symptom following injury to the head, brain, or
      neck. Although studies of central nervous system abnormalities in headache
      sufferers have emerged in recent years, less is known about the associated
      functional impairments. The research literature addressing neuropsychological
      consequences of headache has been far from conclusive. Migraine has been most
      extensively studied, with some consistent evidence of subtle but potentially
      significant changes in cognition occurring during and between migraine episodes.
      It also appears likely that migraine patients with aura experience more
      neuropsychological deficits than those without aura. While the literature devoted
      to understanding the neurocognitive profile of migraine sufferers is growing,
      much less research has addressed the neuropsychology of tension-type headache and
      posttraumatic headache (PTHA). There is some suggestion of poorer
      neuropsychological function in tension-type headache than controls, but the
      evidence is inconclusive. The PTHA population is highly varied in degree and
      location of trauma, preexisting headache condition, and other injury-related
      variables, allowing little generalization across studies. This paper summarizes
      research regarding the cognitive symptoms associated with migraine, tension-type
      headache, and PTHA, provides an overview of the cognitive side effects of
      headache medications, and addresses clinical implications and priorities for
      future research.

PMID- 17040334
TI  - Understanding psychological stress, its biological processes, and impact on
      primary headache.
AB  - Psychological stress is generally acknowledged to be a central contributor to
      primary headache. Stress results from any challenge or threat, either real or
      perceived, to normal functioning. The stress response is the body's activation of
      physiological systems, namely the hypothalamic-pituitary-adrenal axis, to protect
      and restore functioning. Chronic activation of the stress response can lead to
      wear and tear that eventually can predispose an individual to disease. There are
      multiple ways that stress and headache are closely related. Stress can (a) be a
      predisposing factor that contributes to headache disorder onset, (b) accelerate
      the progression of the headache disorder into a chronic condition, and (c)
      precipitate and exacerbate individual headache episodes. How stress impacts
      headache is not often understood. However, stress is assumed to affect primary
      headache by directly impacting pain production and modulation processes at both
      the peripheral and central levels. Stress can also independently worsen headache
      related disability and quality of life. Finally, the headache experience itself
      can serve as a stressor that compromises an individual's health and well-being.
      With the prominent role that stress plays in headache, there are implications for
      the evaluation of stress and the use of stress reduction strategies at the
      various stages of headache disorder onset and progression. Future directions can
      help to develop a better empirical understanding of the pattern of the stress and
      headache connections and the mechanisms that explain the connections. Further
      research can also examine the interactive effects of stress and other factors
      that impact headache disorder onset, course, and adjustment.

PMID- 17040335
TI  - Behavioral facilitation of medical treatment for headache--part I: Review of
      headache treatment compliance.
AB  - Noncompliance or nonadherence with medical regimens represents a major challenge
      to the practice of medicine including the treatment of headache. Indeed,
      medication use patterns are particularly relevant to headache because of the
      potential for headache therapies to induce medication-overuse headache. Previous
      research has demonstrated that adherence to long-term medication therapy for
      various chronic illnesses averages only about 50%. The rate of adherence among
      headache patients has been found to be similarly poor. Misuse or overuse of
      symptomatic medication has been demonstrated to contribute to treatment failure,
      and one-fourth to one-half of patients are noncompliant with prophylactic
      headache medications and at least 40% nonadherent with appointment-keeping.
      Adherence declines with more frequent and complex dosing regimens, side effects,
      and costs, and is subject to a wide range of psychosocial influences. Subjective
      reports of adherence are likely not only to overestimate but also to be
      discordant with more objective measurements. As the first of 2 articles, this
      paper describes the problem of noncompliance in medical practice and reviews
      literature addressing compliance specific to headache management. A companion
      paper (Behavioral Facilitation of Medical Treatment for Headache--Part II:
      Theoretical Models and Behavioral Strategies for Improving Adherence) summarizes
      social learning models proposed to characterize the multiple determinants of
      adherence and guide behavioral adherence-enhancing interventions, and then
      presents cognitive and behavioral strategies that may facilitate treatment
      adherence with headache patients.

PMID- 17040336
TI  - Behavioral facilitation of medical treatment for headache--part II: Theoretical
      models and behavioral strategies for improving adherence.
AB  - This is the second of 2 articles addressing the problem of noncompliance in
      medical practice and, more specifically, compliance with headache treatment. The
      companion paper describes the problem of noncompliance in medical practice and
      reviews literature addressing compliance in headache care (Behavioral
      Facilitation of Medical Treatment for Headache--Part I: Review of Headache
      Treatment Compliance). The present paper first summarizes relevant health
      behavior theory to help account for the myriad biopsychosocial determinants of
      adherence, as well as patient's shifting responsiveness or "readiness for change"
      over time. Appreciation of health behavior models may assist in optimally
      tailoring interventions to patient needs through instructional, motivational, and
      behavioral treatment strategies. A wide range of specific cognitive and
      behavioral compliance-enhancing interventions are described, which may facilitate
      treatment adherence among headache patients. Strategies address patient
      education, patient/provider interaction, dosing regimens, psychiatric
      comorbidities, self-efficacy enhancement, and other behavioral interventions.

PMID- 17040337
TI  - Headache and psychological functioning in children and adolescents.
AB  - Headache can affect all aspects of a child's functioning, leading to negative
      affective states (eg, anxiety, depression, anger) and increased psychosocial
      problems (for instance, school absences, problematic social interactions). For
      children and adolescents who experience frequent headache problems, comorbid
      psychological issues are a well-recognized, but poorly understood, clinical
      phenomenon. The confusion surrounding the relationship between pediatric headache
      and psychopathology exists for several reasons. First, in some cases, headache
      has been inappropriately attributed to psychological or personality features
      based on anecdotal observations or interpretations that go beyond the available
      data. Additionally, measures of psychopathology have not always adhered to the
      American Psychiatric Association's diagnostic criteria, thus reducing the
      reliability of diagnostic judgments. Furthermore, the diagnosis of headache has
      not always followed standard criteria, and has been complicated by the emergence
      of new terms and evolving measures. Finally, methodological shortcomings, such as
      incomplete descriptions of the procedures and criteria used for the study,
      inadequate descriptions of headache severity, lack of a control group for
      comparison with individuals without headaches, reliance primarily on cross
      sectional research designs that are often discussed with inferences to causal
      hypotheses, and the use of unstandardized assessment measures, have significantly
      limited the validity of research findings. The goal of the current review is to
      examine the extant literature to provide the most up-to-date picture on what the
      research has made available about the magnitude, specificity, and causes of
      psychopathology in children and adolescents with headache, in an effort to
      further elucidate their relationship and prompt a more methodologically rigorous
      study of these issues.

PMID- 17040338
TI  - The comorbidity of headache with other pain syndromes.
AB  - In this article, we consider the possible reasons and supporting evidence for the
      comorbidity of chronic pain conditions. To simplify the discussion, we primarily
      focus on the epidemiology of headache with other pain conditions, dividing
      studies into those based on children or adolescents and those based on adults. We
      consider exogenous and endogenous factors, and methodological challenges, in
      understanding whether and how 2 pain conditions may be related.

PMID- 17040339
TI  - Topiramate prophylaxis and response to triptan treatment for acute migraine.
AB  - OBJECTIVE: To evaluate the effect of topiramate migraine prophylaxis on subject
      responsiveness to triptans used for acute symptomatic migraine treatment.
      BACKGROUND: Clinical experience suggests that prophylactic migraine treatment may
      enhance the efficacy of symptomatic medications used to treat acute migraine
      attacks. METHODS: This open-label, single-arm multicenter study consisted of a 6
      week baseline period followed by a 16-week topiramate treatment period. Subjects
      meeting International Headache Society (IHS) criteria for migraine with and
      without aura signed consent and entered the baseline period. Those with 3 to 12
      migraine periods per month during baseline received topiramate prophylactic
      treatment. Only patients who completed at least 12 weeks of topiramate treatment
      were included in the data analysis. RESULTS: Of 55 patients screened, 40 subjects
      entered the topiramate treatment period and 21 subjects received at least 12
      weeks of treatment. Mean final dose of topiramate was 124 mg per day (range 50 to
      200 mg per day). During the baseline period, the mean percentage of attacks
      rendered pain-free at 2 hours for the 21 subjects was 46.9% (SD = 31.9), while
      during the topiramate treatment period it was 44.6% (SD = 32.2) (P= .8). On
      topiramate, after the first 8 weeks of dosage titration, patients experienced a
      mean of 3.68 migraine attacks/month, compared to 4.31 during the baseline period
      (P < .03). Thirteen subjects discontinued because of adverse events. The most
      commonly reported adverse events were paresthesia, fatigue, anxiety, and
      dizziness. CONCLUSION: Although topiramate prophylaxis did reduce migraine attack
      frequency, in this pilot study topiramate prophylactic migraine treatment did not
      increase the proportion of patients pain-free 2 hours after symptomatic triptan
      therapy.

PMID- 17040340
TI  - Visual stimuli are common triggers of migraine and are associated with pattern
      glare.
AB  - OBJECTIVE: To investigate the associations between interictal pattern glare,
      visual stress, and visual triggers of migraine. BACKGROUND: There has been
      relatively little research on the visual stimuli that can trigger migraine
      episodes. This is surprising, since if practitioners can obviate such triggers,
      then some attacks may be prevented. The existing literature suggests that
      patients who are prone to visually triggered migraines report more illusions on
      viewing striped patterns ("pattern glare") and that colored filters may be an
      effective intervention for these people. METHODS: Headache symptoms and headache
      triggers were investigated in migraine and control groups in 2 separate
      experiments. In one experiment, we also determined, for each participant, pattern
      glare, whether it was reduced by colored filters and, if so, what the optimum
      color of filter was. Color vision was also assessed with the D15 test. RESULTS:
      People with migraine saw significantly more illusions on viewing each striped
      pattern and experienced greater pattern glare. They were also more likely to
      select a colored filter to aid visual comfort, particularly colors in the blue-to
      green sector of the spectrum. Color vision was impaired subtly but significantly
      in migraine. Principal component analyses grouped common headache triggers into 5
      broadly equal components: food, visual triggers, alcohol, stress and tiredness,
      and the environment. In a second analysis, the overall number of illusions seen
      in striped patterns was associated with visual triggers while pattern glare, use
      of colored filters, and interictal light sensitivity together formed a sixth
      component interpreted as visual stress. CONCLUSIONS: It is suggested that
      clinicians should ask migraine patients whether visual stimuli trigger their
      migraine, about interictal visual symptoms, and use the pattern glare test to
      ensure that those who may benefit from optometric interventions are appropriately
      managed.

PMID- 17040341
TI  - Treatment of headaches in the ED with lower cervical intramuscular bupivacaine
      injections: a 1-year retrospective review of 417 patients.
AB  - OBJECTIVE: The primary objective of this retrospective chart review is to
      describe 1 year's experience of an academic emergency department (ED) in treating
      a wide spectrum of headache classifications with intramuscular injections of 0.5%
      bupivacaine bilateral to the spinous process of the lower cervical vertebrae.
      BACKGROUND: Headache is a common reason that patients present to an ED. While
      there are a number of effective therapeutic interventions available for the
      management of headache pain, there clearly remains a need for other treatment
      options. The intramuscular injection of 1.5 mL of 0.5% bupivacaine bilateral to
      the sixth or seventh cervical vertebrae has been used to treat headache pain in
      our facility since July 2002. The clinical setting for the study was an academic
      ED with an annual volume of over 75,000 patients. METHODS: We performed a
      retrospective review of over 2805 ED patients with the discharge diagnosis of
      headache and over 771 patients who were coded as having had an anesthetic
      injection between June 30, 2003 and July 1, 2004. All adult patients who had
      undergone paraspinous intramuscular injection with bupivacaine for the treatment
      of their headache were gleaned from these 2 larger databases and were included in
      this retrospective chart review. A systematic review of the medical records was
      accomplished for these patients. RESULTS: Lower cervical paraspinous
      intramuscular injections with bupivacaine were performed in 417 patients.
      Complete headache relief occurred in 271 (65.1%) and partial headache relief in
      85 patients (20.4%). No significant relief was reported in 57 patients (13.7%)
      and headache worsening was described in 4 patients (1%). Overall a therapeutic
      response was reported in 356 of 417 patients (85.4%). Headache relief was
      typically rapid with many patients reporting complete headache relief in 5 to 10
      minutes. Associated signs and symptoms such as nausea, vomiting, photophobia,
      phonophobia, and allodynia were also commonly relieved. CONCLUSION: Our
      observations suggest that the intramuscular injection of small amounts of 0.5%
      bupivacaine bilateral to the sixth or seventh cervical spinous process appears to
      be an effective therapeutic intervention for the treatment of headache pain in
      the outpatient setting.

PMID- 17040342
TI  - Reversible anorgasmia with topiramate therapy for headache: a report of 7
      patients.
AB  - OBJECTIVE: To describe 7 patients who developed new onset anorgasmia while using
      topiramate therapy for migraine prophylaxis. BACKGROUND: Topiramate is an
      effective drug for the prevention of migraine headaches. Though it is generally
      well tolerated, it may be associated with a dose-related anorgasmia. METHODS:
      Case reports. RESULTS: Seven patients (5 women, 2 men), between the ages of 40
      and 62, developed anorgasmia while using topiramate for headache prevention. Four
      women and 2 men had migraine without aura, and 1 woman had migraine with aura.
      None had a prior history of anorgasmia or sexual dysfunction. Doses associated
      with this side effect ranged from 45 to 200 mg daily. All subjects had symptom
      resolution. Six patients had resolution within 7 days of discontinuing or
      decreasing the medication; the exact time frame of resolution for the seventh
      patient is unknown. CONCLUSION: In our series, anorgasmia was a reversible, dose
      related adverse effect of topiramate. Physicians need to be aware of the
      potential for topiramate to cause sexual side effects, and should inquire about
      these symptoms in patients for whom this agent has been prescribed.

PMID- 17040343
TI  - An engineer's 6-year headache diary.

PMID- 17040344
TI  - Intracranial hypotension following chiropractic spinal manipulation.
AB  - We report a case of intracranial hypotension caused by chiropractic manipulation
      which, in contrast to previously reported cases, documents the location of the
      cerebrospinal fluid leak by radionuclide cisternography. Cervical spinal
      manipulation produced a remote lumbar dural tear in our patient. Spinal magnetic
      resonance imaging may falsely localize the dural tear in this condition. Although
      conservative management is often sufficient, precise localization is required for
      more invasive therapies.

PMID- 17040345
TI  - Trigeminal neuralgia in wind musicians.
AB  - The author reports 3 patients with trigeminal neuralgia whose pain was triggered
      by musical performance. Use of the muscles of embouchure activated the trigger
      zone when playing the clarinet, saxophone, flute, piccolo, trombone, or
      whistling. In each case, the location of the trigger zone was perioral,
      regardless of which division of the trigeminal nerve emanated pain. Trigeminal
      neuralgia is a particularly disabling affliction when it occurs in wind
      musicians.

PMID- 17040346
TI  - Subcortical lesions in migraine: are they related to mitochondrial dysfunction?

PMID- 17040347
TI  - Migraine prevention.

PMID- 17040348
TI  - Behavioral headache treatment: modest costs, demonstrated long-term
      effectiveness.

PMID- 17040351
TI  - Time for a medical educational change in time.

PMID- 17040352
TI  - Liver biopsy: is it still relevant?

PMID- 17040353
TI  - Twenty-year audit of percutaneous liver biopsy in a major Australian teaching
      hospital.
AB  - BACKGROUND: To examine the changes in indications, patient characteristics,
      safety and outcomes in consecutive patients undergoing percutaneous core liver
      biopsies in a major Australian teaching hospital over a period of two decades.
      METHODS: A retrospective audit was carried out on all percutaneous core liver
      biopsies from a single institution between 1996 and 2005. This was combined with
      10 years of data already reported on for the years 1986-1995 to detect trends in
      indications and outcomes. RESULTS: Medical records from 1398 patients were
      included for analysis. Over a 20-year period, the most common indications for
      liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver
      function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes
      of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients
      had an abnormal baseline coagulation profile; a significant risk for major
      haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in
      inpatients with major comorbidities. Minor complications occurred in 13.6% of
      patients, with multiple passes a significant risk factor. Whereas the overall
      major and minor complication rates were independent of operator experience
      inadequate specimens were more frequently obtained by the registrar. CONCLUSION:
      This large series extending over two decades shows that despite advances in
      biopsy techniques, the rates of both minor and major complications remain
      significant. Of particular concern are the procedure-related deaths. Identifying
      factors that may increase risk requires further scrutiny and careful patient
      selection needs to be undertaken.

PMID- 17040355
TI  - Access to stroke care units in Australian public hospitals: facts and temporal
      progress.
AB  - BACKGROUND: There is level I evidence that management of stroke patients in
      stroke units (SU) improves outcomes (death and institutionalization) by
      approximately 20%. In Australia, there is uncertainty as to the proportion of
      incident cases that have access to SU. Recent national and State-based policy
      initiatives to increase access to SU have been taken. However, objective evidence
      related to SU implementation progress is lacking. The aims of the study were (i)
      to determine the number of SU in Australian acute public hospitals in 2004, (ii)
      to describe hospitals according to national SU policy criteria and (iii) to
      compare results to the 1999 survey to track progress. METHODS: The method used in
      the study was a cross-sectional, postal survey technique. The participants were
      clinical representatives considered appropriate to describe stroke care within
      survey hospitals. RESULTS: The outcome of the study was presence of a SU
      according to an accepted definition. Response rate was 261/301 (87%). Sixty-one
      sites (23%) had either a SU and/or a dedicated stroke team. Fifty sites claimed
      to have a SU (19%). New South Wales with 23 had the most number of SU. Based on
      policy criteria, up to 64 sites could have a SU. In 1999, there were 35 public
      hospitals with a SU. CONCLUSION: Access to SU in Australian public hospitals
      remains low compared with other countries (Sweden, 70%). Implementation
      strategies supported by appropriate health policy to improve access are needed.

PMID- 17040356
TI  - Comparison and validation of three measures of quality of life in patients with
      pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension, when advanced, markedly limits exercise
      capacity, activities of daily living and quality of life (QoL). No measure of QoL
      has yet been validated for the assessment of pulmonary hypertension. The aim of
      the study was to compare the validity of the Minnesota Living with Heart Failure
      (MLwHF) questionnaire, the Short Form-36 (SF-36) questionnaire and the Australian
      Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment.
      METHODS: Eighty-three patients were enrolled in three studies of pulmonary
      hypertension treatment (treprostinil, bosentan and sildenafil). They were
      assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and
      bosentan groups also had 6 and 12 months' data. Twenty-one patients in the
      sildenafil trial completed concurrently, the SF-36 and AQoL measures at baseline
      and 3 months. QoL scores were correlated with the 6-min walk test distance, New
      York Heart Association functional class and right heart catheter-derived
      haemodynamic parameters of the disease for all matching time points and for
      changes in scores and clinical measurements over time. RESULTS: The MLwHF and SF
      36 scores correlated well with the 6-min walk test distance and New York Heart
      Association functional class, but did not correlate with haemodynamic
      measurements. MLwHF and SF-36 scores also correlated with the rate of change of
      the 6-min walk test distance and New York Heart Association functional class over
      time. CONCLUSION: The MLwHF questionnaire and SF-36 are useful tools for the
      assessment of QoL in pulmonary hypertension and may be useful in the ongoing
      evaluation of QoL in the treatment and study of pulmonary hypertension.

PMID- 17040357
TI  - Information sources used by New South Wales cancer clinicians: a qualitative
      study.
AB  - BACKGROUND: This study identified (i) information sources used by cancer
      clinicians to guide pharmacological treatments, (ii) utilization of, and opinions
      about, online information sources and (iii) clinicians' ability to access a
      specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin's
      Lymphoma). The work was carried out before activation of the Cancer Institute New
      South Wales Standard Cancer Treatment (CI-SCaT) programme. METHODS: We conducted
      semistructured interviews with a purposeful sample of senior and junior doctors,
      nurses and pharmacists treating adult cancer patients (n = 32) in eight New South
      Wales public hospitals. RESULTS: Information seeking processes are context
      specific and vary from clinician to clinician and ward to ward. Clinicians use
      human, electronic and printed information sources at, or close to, the point of
      patient care; however, experienced colleagues are preferred where information is
      needed quickly or in unfamiliar clinical situations. Barriers to using online
      cancer information are environmental (hardware, connection speeds, time),
      personal (poor computer literacy and lack of awareness of appropriate sites) and
      economic (costs of journal subscriptions). Just over half of participants were
      able to locate a specific cancer protocol and none of these protocols was fully
      consistent with CI-SCaT recommendations. CONCLUSION: There is no standardized
      approach to the pharmacological treatment of cancer patients in this sample of
      New South Wales clinicians. CI-SCaT will fill a gap with respect to standardizing
      oncology treatment. However, to ensure maximal CI-SCaT uptake, implementation
      plans should harness positive behavioural influences and attempt to modify the
      negative forces that act on hospital clinicians in their day-to-day work.

PMID- 17040358
TI  - Information from the Internet: attitudes of Australian oncology patients.
AB  - BACKGROUND: Patients require accurate information about their illness to make
      informed decisions. Many sources of information exist, although reliability is
      variable. Our objective was to investigate information seeking behaviour and
      attitudes toward health-related information from the Internet in a sample of
      Australian oncology patients. METHOD: During their outpatient attendance, 109
      patients completed a self-administered paper-pen format questionnaire. They were
      required to have a recent cancer diagnosis (<6 months ago) adequate English and
      no cognitive impairment. RESULTS: Seventy-four per cent of questionnaires were
      returned. The majority of patients (78%) wanted as much information about their
      cancer diagnosis as possible and 90% reported receiving adequate information from
      their treating team. Despite this, more than half actively searched for
      additional information, with 77% using the Internet. Patients were trusting of
      information obtained from the Internet. More than half of information searchers
      discussed information obtained in their search with a health professional. The
      majority of patients did not believe that information searching adversely
      affected the doctor-patient relationship. CONCLUSION: Information searching is
      common in ambulatory Australian oncology patients, with the Internet being a
      frequently used resource. To ensure patients find reliable and relevant
      information and to minimize the risk of harm, health professionals involved in
      treating oncology patients should provide guidance in finding information sources
      and assistance in interpreting the information obtained.

PMID- 17040359
TI  - Irritable bowel syndrome.
AB  - Conceptually, the irritable bowel syndrome (IBS) has been considered a brain-gut
      functional disorder, but this paradigm is under serious challenge. There is
      increasing evidence that organic disease of the gastrointestinal tract can be
      identified in subsets of patients who fulfil the Rome criteria for IBS. Evidence
      for subtle inflammatory bowel disease, serotonin dysregulation, bacterial
      overgrowth and central dysregulation continue to accumulate. The underlying
      causes of IBS remain to be adequately identified, but postinfectious IBS is a
      clear-cut entity. Furthermore, a genetic contribution to IBS also seems likely.
      Diagnosis continues to be based on the symptom profile and the absence of alarm
      features. A heightened awareness of coeliac disease masquerading as IBS is
      becoming accepted. Management remains largely based on symptomatic rather than on
      disease-modifying therapy, but this is likely to change in the near future. Here,
      recent advances in the pathophysiology and management of IBS are considered.

PMID- 17040360
TI  - Bronchiectasis.
AB  - Bronchiectasis is generally classified into cystic fibrosis and non-cystic
      fibrosis bronchiectasis. This review article describes non-cystic fibrosis
      bronchiectasis in adults. Bronchiectasis can be considered a heterogeneous
      condition characterized by irreversible airway dilatation with chronic bronchial
      infection/inflammation. It remains a common condition and is a major cause of
      respiratory morbidity. Many factors are associated with bronchiectasis, but most
      commonly patients will have idiopathic disease. Important clinical findings
      include chronic productive cough, rhinosinusitis, fatigue and bi-basal crackles.
      Patients have usually had symptoms for many years. Diagnosis is confirmed by high
      resolution computed tomography scanning using standardized criteria. Spirometry
      shows moderate airflow obstruction and there is a high prevalence of bronchial
      hyperreactivity. The most common pathogens are non-typeable Haemophilus
      influenzae and Pseudomonas aeruginosa. There may be considerable overlap with
      other chronic airway diseases. Treatment regimens are still not well defined.
      Patients tend to have ongoing symptoms and decline in respiratory function
      despite treatment.

PMID- 17040361
TI  - Thyroid hormone resistance: the role of mutational analysis.
AB  - The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a
      patient with normal or increased thyroid-stimulating hormone is unexpected and
      presents a differential diagnosis between a thyroid-stimulating hormone-secreting
      pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory
      artefact. Without careful clinical and biochemical evaluation, errors may occur
      in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid
      hormone receptor beta gene results in generalized tissue resistance to thyroid
      hormone. As the pituitary gland shares in this tissue resistance, euthyroidism
      with a normal thyroid-stimulating hormone is usually maintained by increased
      thyroid hormones. To date, we have identified eight pedigrees in New Zealand with
      mutations in the thyroid hormone receptor beta gene, including two novel
      mutations. Mutational analysis of the thyroid hormone receptor beta gene allows
      definitive diagnosis of RTH, potentially avoiding the need for protracted and
      expensive pituitary function testing and imaging. Mutational analysis also
      enables family screening and may help to avoid potential misdiagnosis and
      inappropriate treatment.

PMID- 17040362
TI  - Acute copper toxicity following copper glycinate injection.
AB  - We present a patient who developed multi-organ failure due to severe copper
      toxicity following attempted suicide by s.c. injection of copper glycinate. Acute
      copper toxicity is rare in the developed world, although it occurs more
      frequently in developing world countries, where it is a common mode of suicide.
      Acute toxicity usually results from oral ingestion and there are several local
      and systemic effects. Specific management can be difficult as there is little
      evidence regarding the efficacy of chelating agents in acute toxicity.

PMID- 17040363
TI  - Fulminant methicillin-sensitive Staphylococcus aureus infection in a healthy
      adolescent, highlighting 'Panton-Valentine leucocidin syndrome'.
AB  - A 14-year-old immunocompetent adolescent presented systemically unwell with left
      knee septic arthritis. Within several days, disseminated bone and soft tissue
      collections became evident, associated with deep venous thrombosis and pulmonary
      involvement. Methicillin-sensitive Staphylococcus aureus was isolated, harbouring
      Panton-Valentine leucocidin genes. Aggressive antibiotic and surgical therapies
      eventually lead to recovery. Intrafamilial spread of the pathogenic isolate was
      shown by household screening. This presentation is consistent with 'PVL Syndrome'
      and is typical of severe S. aureus infection emerging in young populations
      globally.

PMID- 17040364
TI  - Diabetic muscle infarction.

PMID- 17040365
TI  - Anomalous origin of the right coronary artery from the left anterior descending
      artery: a rare subtype of single coronary artery anomaly.

PMID- 17040366
TI  - Grey-Turner sign after intra-aortic balloon pump insertion.

PMID- 17040367
TI  - Hyperandrogenism in a patient with previous colorectal cancer.

PMID- 17040368
TI  - Hepatotoxicity and valproate therapy.

PMID- 17040369
TI  - Celecoxib allergies and cross-reactivity.

PMID- 17040370
TI  - Australian data do not support current Pharmaceutical Benefits Scheme criteria
      for use of tumour necrosis factor-alpha inhibitors in ankylosing spondylitis.

PMID- 17040371
TI  - Fluctuating asymmetry and developmental instability in evolutionary biology:
      past, present and future.
AB  - The role of developmental instability (DI), as measured by fluctuating asymmetry
      (FA), in evolutionary biology has been the focus of a wealth of research for more
      than half a century. In spite of this long period and many published papers, our
      current state of knowledge reviewed here only allows us to conclude that patterns
      are heterogeneous and that very little is known about the underlying causes of
      this heterogeneity. In addition, the statistical properties of FA as a measure of
      DI are only poorly grasped because of a general lack of understanding of the
      underlying mechanisms that drive DI. If we want to avoid that this area of
      research becomes abandoned, more efforts should be made to understand the
      observed heterogeneity, and attempts should be made to develop a unifying
      statistical protocol. More specifically, and perhaps most importantly, it is
      argued here that more attention should be paid to the usefulness of FA as a
      measure of DI since many factors might blur this relationship. Furthermore, the
      genetic architecture, associations with fitness and the importance of
      compensatory growth should be investigated under a variety of stress situations.
      In addition, more focus should be directed to the underlying mechanisms of DI as
      well as how these processes map to the observable phenotype. These insights could
      yield more efficient statistical models and a unified approach to the analysis of
      patterns in FA and DI. The study of both DI and canalization is indispensable to
      obtain better insights in their possible common origin, especially because both
      have been suggested to play a role in both micro- and macro-evolutionary
      processes.

PMID- 17040372
TI  - Genetic, physiologic and ecogeographic factors contributing to variation in Homo
      sapiens: Homo floresiensis reconsidered.
AB  - A new species, Homo floresiensis, was recently named for Pleistocene hominid
      remains on Flores, Indonesia. Significant controversy has arisen regarding this
      species. To address controversial issues and refocus investigations, I examine
      the affinities of these remains with Homo sapiens. Clarification of problematic
      issues is sought through an integration of genetic and physiological data on
      brain ontogeny and evolution. Clarification of the taxonomic value of various
      'primitive' traits is possible given these data. Based on this evidence and using
      a H. sapiens morphological template, models are developed to account for the
      combination of features displayed in the Flores fossils. Given this overview, I
      find substantial support for the hypothesis that the remains represent a variant
      of H. sapiens possessing a combined growth hormone-insulin-like growth factor I
      axis modification and mutation of the MCPH gene family. Further work will be
      required to determine the extent to which this variant characterized the
      population.

PMID- 17040373
TI  - RNA world - the dark matter of evolutionary genomics.
AB  - For a long time, molecular evolutionary biologists have been focused on DNA and
      proteins, whereas RNA has lived in the shadow of its famous chemical cousins as a
      mere intermediary. Although this perspective has begun to change since genome
      wide transcriptional profiling was successfully extended to evolutionary biology,
      it still echoes in evolutionary literature. In this mini-review, new developments
      of RNA biochemistry and transcriptomics are brought to the attention of
      evolutionary biologists. In particular, the unexpected abundance and functional
      significance of noncoding RNAs is briefly reviewed. Noncoding RNAs control a
      remarkable range of biological pathways and processes, all with obvious fitness
      consequences, such as initiation of translation, mRNA abundance, transposon
      jumping, chromosome architecture, stem cell maintenance, development of brain and
      muscles, insulin secretion, cancerogenesis and plant resistance to viral
      infections.

PMID- 17040374
TI  - Exploring the evolution of environmental sex determination, especially in
      reptiles.
AB  - Environmental sex determination has been documented in a variety of organisms for
      many decades and the adaptive significance of this unusual sex-determining
      mechanism has been clarified empirically in most cases. In contrast, temperature
      dependent sex determination (TSD) in amniote vertebrates, first noted 40 years
      ago in a lizard, has defied a general satisfactory evolutionary explanation
      despite considerable research effort. After briefly reviewing relevant theory and
      prior empirical work, we draw attention to recent comparative analyses that
      illuminate the evolutionary history of TSD in amniote vertebrates and point to
      clear avenues for future research on this challenging topic. To that end, we then
      highlight the latest empirical findings in lizards and turtles, as well as
      promising experimental results from a model organism, that portend an exciting
      future of progress in finally elucidating the evolutionary cause(s) and
      significance of TSD.

PMID- 17040375
TI  - On the logical relationship between natural selection and self-organization.
AB  - Most evolutionary biologists cherish Darwin's theory of natural selection (NS) as
      the process of adaptive evolution more than 140 years after publication of his
      first book on the subject. However, in the past few decades the study of self
      organization (SO) in complex dynamical systems has suggested that adaptation may
      occur through intrinsic reorganization without NS. In this study, we attempt to
      describe the logical framework that relates the general process of SO to the
      specific process of NS. We describe NS as a mechanism that coordinates the
      coevolution of species in an ecosystem to effectively capture, process and
      dissipate solar energy into the earth's shadow. Finally, we conclude that NS is
      an emergent process founded on the same thermodynamic imperatives that are
      thought to underlie all SO. This perspective suggests that the theory of self
      organizing systems offers a broader physical context in which to understand the
      process of NS, rather than contesting it. It even suggests the possibility that
      there may be a physical basis for understanding the origin of the process of NS.
      Rather than being merely a fluke of nature, the origin of NS that may be driven
      by energy flows across gradients.

PMID- 17040376
TI  - The cost of mating rises nonlinearly with copulation frequency in a laboratory
      population of Drosophila melanogaster.
AB  - Previous studies of Drosophila melanogaster have demonstrated a cost to females
      from male courtship and mating, but two critically important parameters remain
      unresolved: (i) the degree to which harm from multiple-mating reduces lifetime
      fitness and (ii) how harm from mating might change with successive matings
      (rematings). Here we use 'laboratory island analysis' to quantify the costs that
      females incur with each remating, in the currency of lifetime fitness and under
      conditions that closely match those to which the flies have adapted for hundreds
      of generations. We experimentally manipulated the number of female matings by
      varying the order of daily 2-h exposures of females to either sperm-less males
      (XO) or intact males (XY). Females that mated more often had substantially
      reduced lifetime fecundity, and importantly, the fitness cost from remating
      rapidly accelerated.

PMID- 17040377
TI  - Contrasting patterns of body shape and neutral genetic divergence in marine and
      lake populations of threespine sticklebacks.
AB  - Comparisons of neutral marker and quantitative trait divergence can provide
      important insights into the relative roles of natural selection and neutral
      genetic drift in population differentiation. We investigated phenotypic and
      genetic differentiation among Fennoscandian threespine stickleback (Gasterosteus
      aculeatus) populations, and found that the highest degree of differentiation
      occurred between sea and freshwater habitats. Within habitats, morphological
      divergence was highest among the different freshwater populations. Pairwise
      phenotypic and neutral genetic distances among populations were positively
      correlated, suggesting that genetic drift may have contributed to the
      morphological differentiation among habitats. On the other hand, the degree of
      phenotypic differentiation (PST) clearly surpassed the neutral expectation set by
      FST, suggesting a predominant role for natural selection over genetic drift as an
      explanation for the observed differentiation. However, separate PST/FST
      comparisons by habitats revealed that body shape divergence between lake and
      marine populations, and even among marine populations, can be strongly influenced
      by natural selection. On the other hand, genetic drift can play an important role
      in the differentiation among lake populations.

PMID- 17040378
TI  - Substantial changes in the genetic basis of tadpole morphology of Rana lessonae
      in the presence of predators.
AB  - Predator-induced morphological plasticity is a model system for investigating
      phenotypic plasticity in an ecological context. We investigated the genetic basis
      of the predator-induced plasticity in Rana lessonae by determining the pattern of
      genetic covariation of three morphological traits that were found to be induced
      in a predatory environment. Body size decreased and tail dimensions increased
      when reared in the presence of preying dragonfly larvae. Genetic variance in body
      size increased by almost an order of magnitude in the predator environment, and
      the first genetic principal component was found to be highly significantly
      different between the two environments. The across environment genetic
      correlation for body size was significantly below 1 indicating that different
      genes contributed to this trait in the two environments. Body size may therefore
      be able to respond to selection independently in the two environments to some
      extent.

PMID- 17040379
TI  - Reproductive tradeoffs and yolk steroids in female leopard geckos, Eublepharis
      macularius.
AB  - Life history theory predicts tradeoffs among reproductive traits, but the
      physiological mechanisms underlying such tradeoffs remain unclear. Here we
      examine reproductive tradeoffs and their association with yolk steroids in an
      oviparous lizard. Female leopard geckos lay two eggs in a clutch, produce
      multiple clutches in a breeding season, and reproduce for several years. We
      detected a significant tradeoff between egg size and the number of clutches laid
      by females during their first two breeding seasons. Total reproductive effort was
      strongly condition-dependent in the first season, but much less so in the second
      season. Although these and other tradeoffs were unmistakable, they were not
      associated with levels of androstenedione, oestradiol, or testosterone in egg
      yolk. Female condition and egg size, however, were inversely related to
      dihydrotestosterone (DHT) levels in egg yolk. Finally, steroid levels in egg yolk
      were not directly related to steroid levels in the maternal circulation when
      follicles were developing, indicating that steroid transfer to eggs is regulated.
      These findings suggest that maternal allocation of DHT could mitigate tradeoffs
      that lead to poor offspring quality (i.e. poor female condition) and small
      offspring size (i.e. small egg size).

PMID- 17040380
TI  - Postzygotic incompatibilities between the pupfishes, Cyprinodon elegans and
      Cyprinodon variegatus: hybrid male sterility and sex ratio bias.
AB  - I examined the intrinsic postzygotic incompatibilities between two pupfishes,
      Cyprinodon elegans and Cyprinodon variegatus. Laboratory hybridization
      experiments revealed evidence of strong postzygotic isolation. Male hybrids have
      very low fertility, and the survival of backcrosses into C. elegans was
      substantially reduced. In addition, several crosses produced female-biased sex
      ratios. Crosses involving C. elegans females and C. variegatus males produced
      only females, and in backcrosses involving hybrid females and C. elegans males,
      males made up approximately 25% of the offspring. All other crosses produced
      approximately 50% males. These sex ratios could be explained by genetic
      incompatibilities that occur, at least in part, on sex chromosomes. Thus, these
      results provide strong albeit indirect evidence that pupfish have XY chromosomal
      sex determination. The results of this study provide insight on the evolution of
      reproductive isolating mechanisms, particularly the role of Haldane's rule and
      the 'faster-male' theory in taxa lacking well-differentiated sex chromosomes.

PMID- 17040381
TI  - A broad-scale analysis of population differentiation for Zn tolerance in an
      emerging model species for tolerance study: Arabidopsis halleri (Brassicaceae).
AB  - Although current knowledge about the overall distribution of zinc (Zn) tolerance
      in Arabidopsis halleri populations is scarce, the species is an emerging model
      for the study of heavy metal tolerance in plants. We attempted to improve this
      knowledge by testing the Zn tolerance of scattered European metallicolous (M) and
      nonmetallicolous (NM) populations of A. h. subsp. halleri and A. h. subsp.
      ovirensis in hydroponic culture. The occurrence of constitutive tolerance was
      unconditionally established in A. h. halleri and tolerance was extended to the
      subspecies ovirensis. M populations were the most tolerant but there was a
      continuous range of variation in tolerance from NM to M populations. Finally,
      relatively high levels of tolerance were detected in some NM populations,
      suggesting that enhanced tolerance could be present at high frequency in
      populations that have not experienced metal exposure. We used our results to
      argue the evolutionary dynamics and origin of Zn tolerance in A. halleri.

PMID- 17040382
TI  - Fitness effects of X chromosome drive in the stalk-eyed fly, Cyrtodiopsis
      dalmanni.
AB  - Sex-ratio (SR) males produce predominantly female progeny because most Y
      chromosome sperm are rendered nonfunctional. The resulting transmission advantage
      of XSR chromosomes should eventually cause population extinction unless
      segregation distortion is masked by suppressors or balanced by selection. By
      screening male stalk-eyed flies, Cyrtodiopsis dalmanni, for brood sex ratio we
      found unique SR alleles at three X-linked microsatellite loci and used them to
      determine if SR persists as a balanced polymorphism. We found that XSR/XST
      females produced more offspring than other genotypes and that SR males had lower
      sperm precedence and exhibited lower fertility when mating eight females in 24 h.
      Adult survival was independent of SR genotype but positively correlated with eye
      span. We infer that the SR polymorphism is likely maintained by a combination of
      weak overdominance for female fecundity and frequency dependent selection acting
      on male fertility. Our discovery of two SR haplotypes in the same population in a
      10-year period further suggests that this SR polymorphism may be evolving
      rapidly.

PMID- 17040383
TI  - Phenotypic plasticity in two marine snails: constraints superseding life history.
AB  - In organisms encountering predictable environments, fixed development is
      expected, whereas in organisms that cannot predict their future environment,
      phenotypic plasticity would be optimal to increase local adaptation. To test this
      prediction we experimentally compared phenotypic plasticity in two rocky-shore
      snail species; Littorina saxatilis releasing miniature snails on the shore, and
      Littorina littorea releasing drifting larvae settling on various shores,
      expecting L. littorea to show more phenotypic plasticity than L. saxatilis. We
      compared magnitude and direction of vectors of phenotypic difference in juvenile
      shell traits after 3 months exposure to different stimuli simulating sheltered
      and crab-rich shores, or wave-exposed and crab-free shores. Both species showed
      similar direction and magnitude of vectors of phenotypic difference with minor
      differences only between ecotypes of the nondispersing species, indicating that
      plasticity is an evolving trait in L. saxatilis. The lack of a strong plastic
      response in L. littorea might be explained by limits rather than costs to
      plasticity.

PMID- 17040384
TI  - Sperm competition in a fish with external fertilization: the contribution of
      sperm number, speed and length.
AB  - The role of sperm number and quality in male competitiveness was investigated
      using in vitro fertilization experiments with bluegill (Lepomis macrochirus).
      Bluegill males use one of three mating tactics: 'sneakers', which streak spawn;
      'satellites', which mimic females; and 'parentals', which are territorial. The in
      vitro experiments mimicked natural spawning by incorporating these males' mean
      proximity to eggs and timing of sperm release. Using a maximum-likelihood
      algorithm, raffle equations were fit to paternity data, which revealed a strong
      effect of sperm number on male competitiveness. There was no difference in sperm
      flagellum length, curvilinear swim speed or path linearity among the three male
      mating types, and these traits did not explain any additional variation in male
      competitiveness. It was estimated that, given closer proximity to eggs,
      satellites need release only 0.34 times as many sperm as parentals to obtain
      equal paternity. Despite being farther from the eggs and releasing sperm about
      half a second after parentals, sneakers need only release 0.58 times as many
      sperm as parentals to obtain equal paternity. Thus, the increased competitiveness
      of sneakers' sperm must come from a component of sperm quality other than speed
      or length.

PMID- 17040385
TI  - Genetics of host plant use and life history in the comma butterfly across Europe:
      varying modes of inheritance as a potential reproductive barrier.
AB  - Comma butterflies (Nymphalidae: Polygonia c-album L.) from one Belgian site and
      three Spanish sites were crossed with butterflies from a Swedish population in
      order to investigate inheritance of female host plant choice, egg mass and larval
      growth rate. We found three different modes of inheritance for the three
      investigated traits. In line with earlier results from crosses between Swedish
      and English populations, the results regarding female oviposition preference
      (choice between Urtica dioica and Salix caprea) showed X-linked inheritance to be
      of importance for the variation between Sweden and the other sites. Egg mass and
      growth rate did not show any sex-linked inheritance. Egg mass differences between
      populations seem to be controlled mainly by additive autosomal genes, as hybrids
      showed intermediate values. The growth rates of both hybrid types following
      reciprocal crossings were similar to each other but consistently higher than for
      the two source populations, suggesting a nonadditive mode of inheritance which is
      not sex-linked. The different modes of inheritance for host plant preference vs.
      important life history traits are likely to result in hybrids with unfit
      combinations of traits. This type of potential reproductive barrier based on
      multiple ecologically important traits deserves more attention, as it should be a
      common situation for instance in the early stages of population divergence in
      host plant usage, facilitating ecological speciation.

PMID- 17040386
TI  - Male Drosophila melanogaster have higher mating success when adapted to their
      thermal environment.
AB  - Adaptation to new environments is a well-documented phenomenon. Individuals from
      populations maintained in a particular environment for multiple generations tend
      to be better able to survive and/or reproduce in that environment than their
      ancestors or other individuals adapted to alternative environments. A third major
      component of fitness, mating success, has not been well studied in replicated
      populations under selection in divergent environments. In this study, we used
      mating trials to compare the mating success of male Drosophila melanogaster
      adapted for 10 years to two different temperatures, 18 and 25 degrees C. In
      competition for female partners, males had significantly higher mating success at
      their adapted temperature compared with males adapted to a different temperature.
      These results are consistent with the notion that those mutations favoured by
      natural selection also tend to be favoured by sexual selection.

PMID- 17040387
TI  - Rapid increase in cuckoo egg matching in a recently parasitized reed warbler
      population.
AB  - Parasitic cuckoos lay eggs that mimic those of their hosts, and such close
      phenotypic matching may arise from coevolutionary interactions between parasite
      and host. However, cuckoos may also explicitly choose hosts in a way that
      increases degree of matching between eggs of cuckoos and parasites, with female
      preference for specific host phenotypes increasing the degree of matching. We
      tested for temporal change in degree of matching between eggs of the parasitic
      European cuckoo (Cuculus canorus) and its reed warbler (Acrocephalus scirpaceus)
      host during 24 consecutive years in a recently parasitized reed warbler
      population. Cuckoo-host egg matching in an ultraviolet-brownness component
      yielding most of the chromatic variance of eggs improved during the study period.
      Improved matching was not due to changes in cuckoo egg phenotype. Cuckoo eggs
      matched host eggs for ultraviolet-brownness within nests irrespective of duration
      of sympatry. Ultraviolet-brownness of cuckoo eggs was similar to that of reed
      warbler eggs at parasitized nests, but differed from that of reed warbler eggs at
      unparasitized nests. These findings provide tentative support for the cuckoo
      preference hypothesis suggesting that cuckoo-host egg matching could partially be
      due to cuckoo females selecting host nests based on the appearance of their eggs.

PMID- 17040388
TI  - Is size-assortative mating important for rapid pigment differentiation in a
      freshwater isopod?
AB  - Identifying mechanisms behind assortative mating is central to the understanding
      of ecological divergence and speciation. Recent studies show that populations of
      the freshwater isopod Asellus aquaticus can rapidly become locally differentiated
      when submerged Chara vegetation expands in lakes. In the novel Chara habitat,
      isopods have become lighter pigmented and smaller than in ancestral reed stands.
      In this study, we used a laboratory multiple-choice experiment to investigate
      assortative mating as a possible prezygotic reproductive barrier between Chara
      and reed isopods. Mating was assortative when Chara isopods were experimentally
      mixed with isopods from an adjacent reed site with large-size individuals,
      suggesting a partial prezygotic reproductive barrier. No deviation from random
      mating could, however, be detected when Chara isopods were mixed with smaller
      sized isopods from another reed site. In both experiments, assortative mating was
      apparently based on size, as Chara isopods were larger and reed isopods smaller
      in mixed pairs than in assortative pairs. Pigmentation did not have any clear
      influence on mating. We suggest that divergence in pigmentation evolved through
      natural selection in conjunction with size-assortative mating indirectly causing
      assortative mating between Chara and reed isopods. Size-assortative mating is
      likely a by-product of natural selection, but its importance may hypothetically
      be transient, if selection erodes the correlation between pigmentation and size
      over time.

PMID- 17040389
TI  - The importance of growth and mortality costs in the evolution of the optimal life
      history.
AB  - A central assumption of life history theory is that the evolution of the
      component traits is determined in part by trade-offs between these traits.
      Whereas the existence of such trade-offs has been well demonstrated, the relative
      importance of these remains unclear. In this paper we use optimality theory to
      test the hypothesis that the trade-off between present and future fecundity
      induced by the costs of continued growth is a sufficient explanation for the
      optimal age at first reproduction, alpha, and the optimal allocation to
      reproduction, G, in 38 populations of perch and Arctic char. This hypothesis is
      rejected for both traits and we conclude that this trade-off, by itself, is an
      insufficient explanation for the observed values of alpha and G. Similarly, a
      fitness function that assumes a mortality cost to reproduction but no growth cost
      cannot account for the observed values of alpha. In contrast, under the
      assumption that fitness is maximized, the observed life histories can be
      accounted for by the joint action of trade-offs between growth and reproductive
      allocation and between mortality and reproductive allocation (Individual Juvenile
      Mortality model). Although the ability of the growth/mortality model to fit the
      data does not prove that this is the mechanism driving the evolution of the
      optimal age at first reproduction and allocation to reproduction, the fit does
      demonstrate that the hypothesis is consistent with the data and hence cannot at
      this time be rejected. We also examine two simpler versions of this model, one in
      which adult mortality is a constant proportion of juvenile mortality
      [Proportional Juvenile Mortality (PJM) model] and one in which the
      proportionality is constant within but not necessarily between species [Specific
      Juvenile Mortality (SSJM) model]. We find that the PJM model is unacceptable but
      that the SSJM model produces fits suggesting that, within the two species
      studied, juvenile mortality is proportional to adult mortality but the value
      differs between the two species.

PMID- 17040390
TI  - Adaptive evolution of the Bordetella autotransporter pertactin.
AB  - The virulence factor pertactin is expressed by the closely related pathogens
      Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.
      Pertactin is an autotransporter involved in adherence of Bordetella species to
      the lung epithelium of mammalian hosts, and it is an important component of most
      current acellular pertussis vaccines. These three species produce immunologically
      distinct pertactin molecules, resulting in a lack of cross-protection against B.
      parapertussis and probably also against B. bronchiseptica. Variation in pertactin
      is not only inter-specific, but also occurs between isolates from the same
      species. Knowledge about codons that are under positive selection could
      facilitate the development of more broadly protective vaccines. Using different
      nucleotide substitution models, pertactin genes from B. bronchiseptica, B.
      parapertussis and B. pertussis were compared, and positively selected codons were
      identified using an empirical Bayesian approach. This approach yielded 15 codons
      predicted to be under diversifying selection pressure. These results were
      interpreted in an immunological context and may help in improving future
      pertussis vaccines.

PMID- 17040391
TI  - On the track of the Red Queen: bark beetles, their nematodes, local climate and
      geographic parthenogenesis.
AB  - Geographic parthenogenesis has been explained as resulting from parasite pressure
      (Red Queen hypothesis): several studies have found high degrees of sexuals where
      the prevalence of parasites is high. However, it is important to address whether
      prevalence of parasites mirrors risk of infection. We explored geographic
      parthenogenesis of Ips acuminatus bark beetles and their nematodes. Local climate
      is crucial for nematode stages outside the host, in spring and summer, and
      prevalence should thus be associated with those temperatures if prevalence
      reliably reflects exposure risk across populations. This was the case; however,
      high prevalence of a virulent nematode species was not associated with many
      sexuals, whereas highly sexual populations were characterized by high infection
      risk of benign nematodes. Low virulence of the latter makes Red Queen dynamics
      unlikely. Geographical patterns of parthenogenesis were instead associated with
      winter temperature and variance in temperature.

PMID- 17040392
TI  - Resistance in introduced populations of a freshwater snail to native range
      parasites.
AB  - Introduced species provide an opportunity to examine responses to novel
      ecological conditions, in particular to the absence of co-evolved enemies.
      Introduced populations could evolve lower investment in resistance or could down
      regulate their immune system as a plastic response to enemy absence. The response
      might have consequences for the success of introduced species. Assuming a trade
      off between resistance and traits related to demographic success, an evolved
      change or reallocation from resistance could increase the chances of invasions.
      On the other hand, introduced populations could have increased resistance as a
      correlate of greater vigour and competitive ability among successful invaders
      [Sampling Bias hypothesis (SBH)]. These hypotheses make different predictions
      about investment in resistance in introduced populations. Using a New Zealand
      clonal snail (Potamopyrgus antipodarum), we examined the resistance of three
      introduced genotypes (one from the US and two from Europe) to several populations
      of a native range parasite (Microphallus sp.). One genotype (Euro A) was
      resistant to all native range parasite populations, consistent with the SBH.
      However, two remaining genotypes (Euro C and US 1) were less susceptible to
      parasite populations that were allopatric to their source populations.
      Furthermore, resistance of one genotype (US 1) collected from the introduced
      range was indistinguishable from its resistance when collected from the range of
      the parasite. Hence, there was no evidence for decreased resistance in the
      absence of native enemies, which is inconsistent with hypotheses that envision
      reduced allocation to resistance or a trade-off between competitive ability and
      resistance.

PMID- 17040393
TI  - Relative number of generations of hosts and parasites does not influence parasite
      local adaptation in coevolving populations of bacteria and phages.
AB  - A potential consequence of host-parasite coevolution in spatially structured
      populations is parasite local adaptation: local parasites perform better than
      foreign parasites on their local host populations. It has been suggested that the
      generally shorter generation times of parasites compared with their hosts
      contributes to parasites, rather than hosts, being locally adapted. We tested the
      hypothesis that relative generation times of hosts and parasites affect local
      adaptation of hosts and parasites, using the bacterium Pseudomonas fluorescens
      and a lytic phage as host and parasite, respectively. Generation times were not
      directly manipulated, but instead one of the coevolving partners was regularly
      removed and replaced with a population from an earlier time point. Thus, one
      partner underwent more generations than the other. Manipulations were carried out
      at both early and later periods of coevolutionary interactions. At early stages
      of coevolution, host and parasites that underwent relatively more generations
      displayed higher levels of resistance and infectivity, respectively. However, the
      relative number of generations that bacteria and phages underwent did not change
      the level of local adaptation relative to control populations. This is likely
      because generalist hosts and parasites are favoured during early stages of
      coevolution, preventing local adaptation. By contrast, at later stages
      manipulations had no effect on either average levels of resistance or
      infectivity, or alter the level of local adaptation relative to the controls,
      possibly because traits other than resistance and infectivity were under strong
      selection. Taken together, these data suggest that the relative generation times
      of hosts and parasites may not be an important determinant of local adaptation in
      this system.

PMID- 17040394
TI  - Increased male mating rate in Drosophila is associated with Wolbachia infection.
AB  - The maternally inherited bacterium Wolbachia pipientis infects 25-75% of
      arthropods and manipulates host reproduction to improve its transmission. One way
      Wolbachia achieves this is by inducing cytoplasmic incompatibility (CI), where
      crosses between infected males and uninfected females are inviable. Infected
      males suffer reduced fertility through CI and reduced sperm production. However,
      Wolbachia induce lower levels of CI in nonvirgin males. We examined the impact of
      Wolbachia on mating behaviour in male Drosophila melanogaster and D. simulans,
      which display varying levels of CI, and show that infected males mate at a higher
      rate than uninfected males in both species. This may serve to increase the spread
      of Wolbachia, or alternatively, may be a behavioural adaptation employed by males
      to reduce the level of CI. Mating at high rate restores reproductive
      compatibility with uninfected females resulting in higher male reproductive
      success thus promoting male promiscuity. Increased male mating rates also have
      implications for the transmission of Wolbachia.

PMID- 17040395
TI  - MHC class I variation associates with parasite resistance and longevity in
      tropical pythons.
AB  - Using restriction fragment length polymorphism (RFLP) we identified 26 unique
      major histocompatibility complex (MHC) genotypes in 104 water pythons. We
      observed a significant independent association between reduced blood parasite
      load (Hepatozoon sp.) and python body length/age, presence of a specific RFLP
      fragment (C-fragment) and the overall number of fragments. The parasite has a
      negative impact on several python life-history traits such as growth, nutritional
      status and longevity. Thus, the C-fragment could be considered a 'good gene' (a
      fitness-enhancing genetic element). However, while the number of fragments
      affected parasite load, the association between level of parasitaemia and
      fragment number was not linear, and, hence, minimum parasite infection level was
      achieved at an intermediate number of fragments. Intermediate MHC fragment
      numbers were also observed among the largest/oldest pythons, suggesting that both
      a specific fragment and intermediate levels of MHC polymorphism enhanced python
      longevity. Thus, our results suggest python MHC is subject to both frequency
      dependent and balancing selection.

PMID- 17040396
TI  - The genetic basis of intrinsic and extrinsic post-zygotic reproductive isolation
      jointly promoting speciation in the lake whitefish species complex (Coregonus
      clupeaformis).
AB  - Understanding the genetic architecture of reproductive barriers and the
      evolutionary forces that drove their divergence represents a considerable
      challenge towards understanding speciation. The objective of this study was to
      determine the genetic basis of intrinsic and extrinsic post-zygotic isolation in
      diverging populations of dwarf and normal lake whitefish with allopatric glacial
      origins. We found that the rate of embryonic mortality was 5.3-6.5 times higher
      in dwarf-normal hybrid backcrosses during development than in F1 dwarf and normal
      crosses. When comparing embryos that died during development against larvae that
      successfully hatched, patterns of Mendelian segregation at 101 loci whose linkage
      is known identified 13 loci distributed over seven linkage groups that exhibited
      significant shifts in segregation ratios leading to significant segregation
      distortion at these loci in the surviving progeny. Controlled crosses and
      quantitative trait loci analysis revealed a significant genetic basis for
      developmental time until emergence, a trait critical to fish larval survival in
      nature. Hatching backcross progeny exhibited asynchronous emergence and
      transgressive segregation, suggesting that extrinsic post-zygotic isolation may
      select against hybridization in specific environmental contexts. Evidence of a
      genetic basis for increased embryonic mortality followed by asynchronous
      emergence indicated that intrinsic and extrinsic mechanisms are not mutually
      exclusive in the formation and maintenance of reproductive isolation, but may be
      jointly promoting population divergence and ultimately speciation.

PMID- 17040397
TI  - Variation in the intensity of inbreeding depression among successive life-cycle
      stages and generations in gynodioecious Silene vulgaris (Caryophyllaceae).
AB  - Inbreeding depression is one of the hypotheses explaining the maintenance of
      females within gynodioecious plant populations. However, the measurement of
      fitness components in selfed and outcrossed progeny depends on life-cycle stage
      and the history of inbreeding. Comparative data indicate that strong inbreeding
      depression is more likely to occur at later life-cycle stages. We used
      hermaphrodite individuals of Silene vulgaris originating from three populations
      located in different valleys in the Swiss Alps to investigate the effect of two
      generations of self- and cross-fertilization on fitness components among
      successive stages of the life cycle in a glasshouse experiment. We detected
      significant inbreeding depression for most life-cycle stages including: the
      number of viable and aborted seeds per fruit, probability of germination, above
      ground biomass, probability of flowering, number of flowers per plant, flower
      size and pollen viability. Overall, the intensity of inbreeding depression
      increased among successive stages of the life cycle and cumulative inbreeding
      depression was significantly stronger in the first generation (delta
      approximately 0.5) compared with the second generation (delta approximately
      0.35). We found no evidence for synergistic epistasis in our experiment. Our
      finding of more intense inbreeding depression during later stages of the life
      cycle may help to explain the maintenance of females in gynodioecious populations
      of S. vulgaris because purging of genetic load is less likely to occur.

PMID- 17040398
TI  - Thermal evolution of pre-adult life history traits, geometric size and shape, and
      developmental stability in Drosophila subobscura.
AB  - Replicated lines of Drosophila subobscura originating from a large outbred stock
      collected at the estimated Chilean epicentre (Puerto Montt) of the original New
      World invasion were allowed to evolve under controlled conditions of larval
      crowding for 3.5 years at three temperature levels (13, 18 and 22 degrees C).
      Several pre-adult life history traits (development time, survival and competitive
      ability), adult life history related traits (wing size, wing shape and wing
      aspect ratio), and wing size and shape asymmetries were measured at the three
      temperatures. Cold-adapted (13 degrees C) populations evolved longer development
      times and showed lower survival at the highest developmental temperature. No
      divergence for wing size was detected following adaptation to temperature
      extremes (13 and 22 degrees C), in agreement with earlier observations, but wing
      shape changes were obvious as a result of both thermal adaptation and development
      at different temperatures. However, the evolutionary trends observed for the wing
      aspect ratio were inconsistent with an adaptive hypothesis. There was some
      indication that wing shape asymmetry has evolutionarily increased in warm-adapted
      populations, which suggests that there is additive genetic variation for
      fluctuating asymmetry and that it can evolve under rapid environmental changes
      caused by thermal stress. Overall, our results cast strong doubts on the
      hypothesis that body size itself is the target of selection, and suggest that pre
      adult life history traits are more closely related to thermal adaptation.

PMID- 17040399
TI  - Frequency-dependent predation and maintenance of prey polymorphism.
AB  - In positive frequency-dependent predation, predation risk of an individual prey
      correlates positively with the frequency of that prey type. In a number of small
      scale experiments individual predators have shown frequency-dependent behaviour,
      often leading to the conclusion that a population of such predators could
      maintain prey polymorphism. Using simulations, I studied the dynamics of
      frequency-dependent predation and prey polymorphism. The model suggests that
      persistence of prey polymorphism decreases with increasing number of predators
      that show frequency-dependent behaviour, questioning conclusions about
      polymorphism based on experiments with few predators. In addition, prey
      population size, prey crypsis, difference in crypsis between prey morphs and the
      way the behaviour was adjusted affected the persistence of polymorphism. Under
      some circumstances prey population remained polymorphic for a shorter time under
      frequency-dependent than under frequency-independent predation. This suggests
      that although positive frequency-dependent predator behaviour may maintain prey
      polymorphism, it is not a sufficient condition for persistent prey polymorphism.

PMID- 17040400
TI  - Unicoloniality, recognition and genetic differentiation in a native Formica ant.
AB  - Some ants have an extraordinary form of social organization, called
      unicoloniality, whereby individuals mix freely among physically separated nests.
      This mode of social organization has been primarily studied in introduced and
      invasive ant species, so that the recognition ability and genetic structure of
      ants forming unicolonial populations in their native range remain poorly known.
      We investigated the pattern of aggression and the genetic structure of six
      unicolonial populations of the ant Formica paralugubris at four hierarchical
      levels: within nests, among nests within the same population, among nests of
      populations within the Alps or Jura Mountains and among nests of the two mountain
      ranges. Ants within populations showed no aggressive behaviour, but recognized
      nonnestmates as shown by longer antennation bouts. Overall, the level of
      aggression increased with geographic and genetic distance but was always
      considerably lower than between species. No distinct behavioural supercolony
      boundaries were found. Our study provides evidence that unicoloniality can be
      maintained in noninvasive ants despite significant genetic differentiation and
      the ability to discriminate between nestmates and nonnestmates.

PMID- 17040401
TI  - Chromosomal basis of viability differences in Tigriopus californicus
      interpopulation hybrids.
AB  - Crosses between populations of Tigriopus californicus result in backcross and F2
      hybrid breakdown for a variety of fitness related measures. The magnitude of this
      hybrid breakdown is correlated with evolutionary divergence. We assessed the
      chromosomal basis of viability differences in nonrecombinant backcross hybrids
      using markers mapped to individual chromosomes. To assess effects of evolutionary
      divergence we crossed one population to three different populations: two
      distantly related (approximately 18% mitochondrial COI sequence divergence) and
      one closely related (approximately 1% mitochondrial COI sequence divergence). We
      found that all three interpopulation crosses resulted in significant deviations
      from expected Mendelian ratios at a majority of the loci studied. In all but one
      case, deviations were due to a deficit of parental homozygotes. This pattern
      implies that populations of T. californicus carry a significant genetic load, and
      that a combination of beneficial dominance and deleterious homozygote
      heterozygote interactions significantly affects hybrid viability. Pairwise tests
      of linkage disequilibrium detected relatively few significant interactions. For
      the two divergent crosses, effects of individual chromosomes were highly
      concordant. These two crosses also showed higher heterozygote excess in females
      than males across the vast majority of chromosomes.

PMID- 17040402
TI  - The design of complex sexual traits in male barn swallows: associations between
      signal attributes.
AB  - Variation in the expression of sexually selected traits among individuals is
      widely investigated on the premise that these traits evolved to signal male
      quality. Significant repeatabilities of sexual signals and their associations
      with condition, mating success, survivorship and age may be the signatures of
      sexual selection. However, little is known about the relationship between these
      sexual attributes. Here we studied 28 acoustic and visual traits in the barn
      swallow, Hirundo rustica, that may potentially function in sexual selection.
      Based on effect sizes calculated at the between-individual level, we assessed the
      relationship between repeatability, condition-dependence, attractiveness, age
      dependence and viability indicator value of sexual traits using sexual signals as
      the units of analyses. Those traits that showed high within-year repeatability
      also showed high between-year repeatability, indicating that between-individual
      variation is consistent within and among seasons. In addition, age-dependence of
      traits, probably causing between-year variation, was negatively related to
      between-year repeatability. Condition-dependence was negatively correlated with
      effect sizes for the extent to which traits predicted viability. Therefore,
      traits that are positively related to immediate condition are those that are
      negatively related to survival, which may be the signature of a trade-off between
      current and future reproductive success ultimately reflecting signal reliability.
      No other significant relationship was found between trait attributes. We conclude
      that multiple sexual signals reflect different aspects of male quality in the
      barn swallow.

PMID- 17040405
TI  - Serotonin transporter gene polymorphisms in irritable bowel syndrome.

PMID- 17040406
TI  - Electrical stimulation - an evolving concept in the treatment of colonic motor
      dysfunctions.
AB  - Electrical stimulation of digestive organs is a new approach for the treatment of
      dismotility-based diseases affecting the gastrointestinal (GI) tract. The most
      significant advancement in this field has been obtained with stomach stimulation.
      As a result, a fully implantable stimulation system to treat gastroparesis - the
      'Enterra' system - is now commercially available. Similarly, electrical
      stimulation of the colon may become a valuable alternative to drug therapy and
      surgical procedures in the treatment of colonic motor dysfunctions. Over the past
      decade, several stimulation patterns to modulate colon motility have been tested
      in animal and human models. The results of these studies are reviewed here in
      connection with aspects regarding physiological mechanisms activated by
      electrical stimulation of the colon.

PMID- 17040407
TI  - Assessment of oesophageal emptying in achalasia patients by intraluminal
      impedance monitoring.
AB  - Oesophageal emptying can be assessed by radiographic and scintigraphic tests with
      radiation exposure or by multichannel intraluminal impedance monitoring (MII).
      The aim of this study was to evaluate the applicability of MII for the assessment
      of oesophageal emptying in achalasia patients. In 10 achalasia patients,
      impedance tracings were scored independently by three observers after ingestion
      of a 100-mL barium bolus. Bolus clearance time (BCT) and height of barium column
      were scored using fluoroscopic images acquired at 20-s intervals. All patients
      showed a low baseline impedance level in the distal oesophagus. Air trapping in
      the proximal oesophagus was detected in nine patients. BCT on MII was similar to
      that on fluoroscopy in 40-70% of the patients. Correlations between height of
      barium on fluoroscopy and fluid level on MII were poor to moderate at different
      time intervals. Concordance (Kendall's coefficient) between the three observers
      for assessment of fluid level on MII was 0.31 (P = 0.04) at 1 and 5 min, 0.26 (P
      = 0.08) at 10 and 0.44 (P = 0.01) at 15 min. We conclude that in achalasia
      patients, low baseline impedance levels and air entrapment in the proximal
      oesophagus limit the value of intraluminal impedance monitoring as a test of
      oesophageal emptying.

PMID- 17040408
TI  - Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic
      analysis for gastro-oesophageal reflux assessment.
AB  - Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro
      oesophageal reflux (GOR) events. Visual analysis of impedance recording requires
      expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR
      assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal
      pH-impedance monitoring. Recordings analysis was performed visually (V) and
      automatically using Autoscan function (AS) of Bioview software. A symptom index
      (SI) > or =50% was considered for a significant association between symptoms and
      reflux events. AS analysis detected more reflux events, especially non-acid,
      liquid, pure gas and proximal events. Detection of oesophageal acid exposure and
      acid reflux events was similar with both analyses. Agreement between V and AS
      analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters.
      During pH-impedance studies, 65 patients reported symptoms. As compared to visual
      analysis, the sensitivity and specificity of a positive SI determined by AS were
      respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux
      and 33% and 87.5% for non-acid reflux. Despite good agreement with visual
      analysis, automatic analysis overestimates the number of non-acid reflux events.
      Visual analysis remains the gold standard to detect an association between
      symptoms and non-acid reflux events.

PMID- 17040409
TI  - Relationship between upper gastrointestinal symptoms and changes in body weight
      in a population-based cohort.
AB  - Obesity has been associated with increased reporting of gastrointestinal (GI)
      symptoms, but whether weight gain or loss causes symptoms is unclear. We studied
      the association between changes in body weight and changes in upper GI symptoms.
      Prospective cohort study on random samples of Olmsted County, MN residents.
      Distinct upper GI symptom complexes [gastro-oesophageal reflux disease (GERD),
      chest pain, dyspepsia- pain predominant, dyspepsia-dysmotility] were defined.
      Subjects with persistent, new-onset or disappearing symptoms were identified as
      cases, subjects with no reported symptoms in any of the surveys served as
      controls. Associations were studied in a logistic regression model, using age,
      gender, baseline Body Mass Index and somatic symptom score as covariates.
      Participants for whom baseline and follow-up data were available (n = 637) had a
      median time between surveys of 10.5 years. Baseline body weight was associated
      with GERD, chest pain and dyspepsia-pain predominant symptom complexes. An
      increase in body weight >10 lb between surveys was associated with new onset of
      dyspepsia-dysmotility (OR 5.57, 95% CI 1.91, 16.2). No association was found
      between weight loss >10 lb and the studied symptom complexes. Moderate body
      weight increases and decreases are generally not associated with upper GI symptom
      changes over time in the general population.

PMID- 17040410
TI  - Serotonin transporter gene polymorphism and irritable bowel syndrome.
AB  - Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT)
      gene may underlie the disturbance in gut function in patients with irritable
      bowel syndrome (IBS). Association studies of SERT polymorphisms and IBS have
      shown diverse results among different countries, which might be due to racial and
      subject composition differences. The aim of this study was to assess the
      potential association between SERT polymorphisms and IBS in Koreans. A total of
      190 IBS patients, who met the Rome II criteria, and 437 healthy controls were
      subjected to genotyping. SERT polymorphisms differed in the IBS and control
      groups (P = 0.014). The SERT deletion/deletion genotype occurred with greater
      frequency in the diarrhoea-predominant IBS group than in the controls. A strong
      genotypic association was observed between the SERT deletion/deletion genotype
      and diarrhoea-predominant IBS (P = 0.012). None of the clinical symptoms analysed
      was significantly associated with the SERT genotypes. The frequency of the SERT
      insertion/insertion genotype was much lower than that of the other two genotypes.
      A significant association was observed between the SERT polymorphism and IBS,
      especially diarrhoea-predominant IBS, suggesting that the SERT gene is a
      potential candidate gene involved in IBS in Korea.

PMID- 17040411
TI  - Influence of alcohol consumption on IBS and dyspepsia.
AB  - The role of alcohol use in irritable bowel syndrome (IBS) and dyspepsia is not
      well understood. We hypothesised that people with psychological distress who
      drink no alcohol, or excess alcohol, are at increased risk of having IBS or
      dyspepsia. Valid gastrointestinal (GI) symptom surveys were mailed to randomly
      selected cohorts of community residents. Associations between IBS, dyspepsia and
      abdominal pain and alcohol use were assessed using logistic regression adjusted
      for a Somatic Symptom Checklist score (SSC). A total of 4390 (80%) responded; of
      these, 10.5% reported IBS, 2% dyspepsia and 22% abdominal pain. Alcohol
      consumption >7 drinks week(-1) was associated with a greater odds for dyspepsia
      (OR 2.3; 95% CI:1.1-5.0) and frequent abdominal pain (OR 1.5; 95% CI: 1.1-2.0)
      but not IBS. However, significant interactions among gender, alcohol use and SSC
      scores were detected (P < 0.005). In females with a low SSC score, consuming
      alcohol > or =7 drinks week(-1) increased the odds of IBS compared to drinking
      alcohol moderately. Alcohol consumption was associated with dyspepsia and
      abdominal pain. A relationship with IBS was identified when interactions with
      somatization and gender were appropriately considered. Whether these associations
      are due to the effects of alcohol on the gut, or a common central mechanism
      remains to be determined.

PMID- 17040412
TI  - Vasoactive intestinal peptide receptor subtypes and signalling pathways involved
      in relaxation of human stomach.
AB  - Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with
      receptors coupled to cAMP- or cGMP-signalling pathways. Their relative
      contribution to human gastric relaxation is unknown. This study aimed at
      investigating, in terms of biological activity, receptor expression and related
      signalling pathways, the action of VIP separately on the human fundus and the
      antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of
      the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53
      +/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both
      fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse
      transcriptase-polymerase chain reaction analysis showed the sole expression of
      VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant
      in the antrum. Functional regional differences in receptor-related signalling
      pathways were found. Activation of the cAMP-pathway by forskolin or its
      inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs)
      inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP
      pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583)
      or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher
      expression of endothelial nitric oxide synthase was found. In conclusion,
      regional differences in VIP action on human stomach are related to distinct
      myogenic properties of SMC of the antrum and the fundus.

PMID- 17040413
TI  - Different susceptibilities of spontaneous rhythmicity and myogenic contractility
      to intestinal muscularis inflammation in the hapten-induced colitis.
AB  - We examined the time-dependent changes in the immunoreactivity of the smooth
      muscle region and the accompanying motility disorder in a hapten-induced rat
      model of colitis. Histological analysis and myeloperoxidase (MPO) activity
      indicated that inflammatory cells infiltrated into the muscle layer at 2 days
      after 2,4,6-trinitrobenzenesulphonic acid (TNBS) treatment. The infiltrated
      immune cells then gradually decreased in number, but were still present at 14
      days. The expression of proinflammatory cytokine mRNAs (TNF-alpha, IL-1beta and
      IL-6) and proteins in the muscle layer was increased at 2 days, then began to
      decrease, returning to control levels at 14 days. The frequency of spontaneous
      rhythmicity was suppressed at 2 and 7 days, and returned to control levels at 14
      days. Consistent with these observations, the immunoreactivity of the
      interstitial cells of Cajal network was disrupted at 2 and 7 days, which then
      gradually reformed at 14 days. On the other hand, the myogenic contractions
      induced by high K(+) and carbachol were decreased at 2 days, and were still
      inhibited at 14 days. These results suggest that spontaneous rhythmicity
      dysfunction may improve more rapidly than myogenic contractility dysfunction in a
      hapten-induced rat model of colitis.

PMID- 17040414
TI  - Supraspinal control of external anal sphincter motility: effects of vesical
      distension in humans and cats.
AB  - A pontine centre located near the micturition centre controlling external anal
      sphincter (EAS) motility via noradrenergic neurones has been described in cats.
      The aim of this study was to determine (i) whether a similar centre controls EAS
      motility in humans and (ii) whether this centre is involved in vesico-sphincteric
      reflexes in cats and humans. The effects of an alpha-1-adrenoceptor antagonist
      (nicergoline) and those of vesical distension on the electrical activity of the
      EAS were studied in paraplegic and non-paraplegic volunteers. The effects of
      vesical distension by injecting saline at physiological levels on the responses
      of the EAS to pudendal nerve stimulation were investigated in intact cats and
      cats with nerve sections. In non-paraplegic subjects, nicergoline and vesical
      distension abolished the activity of the EAS. These effects were no longer
      observed in paraplegic patients. In cats, vesical distension inhibited the reflex
      response of the EAS to pudendal nerve stimulation. This vesico-sphincteric
      reflex, which was no longer observed in spinal animals, persisted after
      nicergoline injection. These findings indicate that in humans, there exists a
      supra-spinal centre facilitating the tonic activity of the EAS via noradrenergic
      neurones not involved in the inhibitory vesico-sphincteric reflex.

PMID- 17040415
TI  - MRI of the stomach in neurogastroenterology.

PMID- 17040417
TI  - Outcomes of low-vision services using optometric and multidisciplinary
      approaches: a non-randomized comparison.
AB  - Consecutive patients (n = 215) who were referred to optometric (55%) or
      multidisciplinary (45%) low-vision services and above 50 years of age were
      recruited from four hospitals in the Netherlands. They completed two vision
      related quality of life questionnaires, the Vision Quality of Life Core Measure
      (VCM1) and the Low Vision Quality of Life Questionnaire (LVQOL), before their
      first visit with low-vision services and 1 year later. At follow-up, patients
      referred to multidisciplinary low-vision services had lower scores on the
      mobility subscale of the LVQOL than patients referred to optometric low-vision
      services [5.3 points; 95% confidence interval (CI): 0.2-10.5]. Paired sample t
      tests for the two groups of patients taken together show improvement for the VCM1
      (3.1 points; 95% CI: 0.6-5.6) and deterioration for the basic aspects of vision
      (3.5 points; 95% CI: 1.1-5.9) and the mobility (6.6 points; 95% CI: 3.7-9.5)
      subscales of the LVQOL. In conclusion, people referred to optometric services
      showed less deterioration in mobility than those referred to multidisciplinary
      services. No differences were observed for any of the other subscales of the
      LVQOL and the VCM1. Future research in this field should include randomized
      controlled designs comparing low-vision services with no treatment or placebo.

PMID- 17040418
TI  - The effect of font and line width on reading speed in people with mild to
      moderate vision loss.
AB  - PURPOSE: The aim of this study was to evaluate the effects of print size,
      typeface, and line width on reading speed in readers with mild to moderate sight
      problems. METHODS: A total of 43 patients, most of whom had mild cataract or
      glaucoma with acuity 6/30 or better (median age = 72; range = 24-88 years), read
      aloud a selection of texts presented randomly in four sizes (10, 12, 14 and 16
      point), for each of four typefaces [Foundry Form Sans (FFS), Helvetica (HV),
      Tiresias PCfont (TPC), Times New Roman (TNR)] at a standard line width of 70
      characters and a viewing distance of 40 cm. A subset of letter sizes and
      typefaces were tested at two additional line widths (35, 90). RESULTS: As
      expected, reading speed increased with print size from a median of 144 words min(
      1) for 10-point text to 163 words min(-1) for 16-point text (repeated measures
      anova, p < 0.0001). There was also a significant effect of typeface with TPC
      being read about 8 words min(-1) faster, on average, than the other fonts (159
      words min(-1) for TPC vs 151 words min(-1) for the other fonts, p < 0.0001).
      However fonts of the same nominal point size were not equivalent in actual size.
      When adjusted for the actual horizontal and vertical space occupied, the
      advantage of TPC was eliminated. There was no effect of line width (p > 0.3).
      Data from the present study were extrapolated to the general population over age
      65. This extrapolation indicated that increasing minimum print size from 10
      points to 16 points would increase the proportion of the population able to read
      fluently (>85 words min(-1)) from 88.0% to 94.4%. CONCLUSION: This study shows
      that line width and typeface have little influence on reading speed in people
      with mild to moderate sight problems. Increasing the minimum recommended print
      size from 10 points to 14 or 16 points would significantly increase the
      proportion of the population able to read fluently.

PMID- 17040419
TI  - Double-masked randomised placebo-controlled trial of the effect of prismatic
      corrections on rate of reading and the relationship with symptoms.
AB  - Practitioners' decisions on when to intervene in decompensated heterophoria are
      often based on symptoms, which are in some cases an unreliable indicator of
      whether an intervention will be helpful. The aim of our study was to determine
      when prismatic corrections improve performance at a measure of dynamic visual
      function: the Wilkins Rate of Reading Test (WRRT). All participants manifested an
      aligning prism (associated heterophoria) on the near Mallett Unit of 0.5Delta or
      greater. There were 80 participants, of whom 58 had exophoria, 15 esophoria, and
      seven hyperphoria. The effect of the aligning prism on the WRRT was compared with
      a control lens using a double-masked randomised design. For exophoria, an
      aligning prism of 2Delta and above has a sensitivity of 67% and a specificity of
      79% for improving performance at the WRRT by 5% or more. It is not possible from
      our data to achieve a good compromise between sensitivity and specificity for the
      other types of heterophoria. Patients in the horizontal (but not vertical)
      heterophoria groups had significantly more symptoms than a control group. The
      patients whose visual performance is improved by prismatic correction are not
      necessarily those who report the most symptoms. Our data suggest that exophoric
      patients of any age are likely to have improved visual performance with an
      intervention if they have an aligning prism of 2Delta or more, even in the
      absence of symptoms. We stress that although the Mallett Unit Fixation Disparity
      test provides useful information, its results need to be considered in the
      overall context of the patient's symptoms, lifestyle, and the results of other
      optometric tests. Although this study evaluated prismatic corrections, we note
      that interventions for decompensated heterophoria include not only prismatic
      corrections, but also eye exercises and refractive modification.

PMID- 17040420
TI  - Screening for Meares-Irlen sensitivity in adults: can assessment methods predict
      changes in reading speed?
AB  - Two methods of assessing candidates for coloured overlays were compared with the
      aim of determining which method had the most practical utility. A total of 58
      adults were assessed as potential candidates for coloured overlays, using two
      methods; a questionnaire, which identified self-reported previous symptoms, and a
      measure of perceptual distortions immediately prior to testing. Participants were
      classified as normal, Meares-Irlen sensitive, and borderline sensitive. Reading
      speed was measured with and without coloured overlays, using the Wilkins Rate of
      Reading Test and the change in speed was calculated. Participants classified as
      normal did not show any significant benefit from reading with an overlay. In
      contrast, a significant reading advantage was found for the borderline and Meares
      Irlen participants. Current symptom rating was found to be a significant
      predictor of the change in reading speed, however the previous symptom rating was
      not found to be a reliable predictor. These data indicate that the assessment of
      perceptual distortions immediately prior to measuring colour preference and
      reading speed is the most meaningful method of assessing pattern glare and
      determining the utility of coloured overlays.

PMID- 17040421
TI  - Dynamics in longitudinal eye movements and corneal shape.
AB  - The magnitude and character of longitudinal movements of the eye were studied in
      the context of high speed videokeratoscopy. It was of interest to determine
      whether these dynamic changes in the eye movements can affect the corneal shape
      and its estimation. A high speed videokeratoscope with a sampling frequency of 50
      Hz was used for measuring the corneal apex movements as well as for measuring
      variations in the best-fit sphere radius and central radius of curvature. The
      magnitude of the measured longitudinal apex movements could reach over 200 microm
      showing a slow trend. The estimated local changes of the apex movements that
      could be associated with the cardiopulmonary system were about 40-50 microm. The
      temporal variations in the equivalent estimated central radius of curvature
      ranged between 10 and 15 microm. Spectral analysis of the longitudinal eye
      movements revealed strong signatures of the pulse and respiration signals as well
      as the assumed blink control signal. No clear association between the
      longitudinal apex movements and the corneal curvature was found. However, very
      slow significant changes in the corneal shape were observed. The central radius
      of curvature of the cornea revealed slow changes of up to 120 microm.
      Understanding the nature of such changes will be of benefit in ophthalmic
      applications requiring highly accurate measurements of corneal shape, such as
      contact lens design and refractive surgery.

PMID- 17040422
TI  - End-box scoring artefact evaluation of the Farnsworth-Munsell 100-Hue colour
      vision test.
AB  - The scoring artefact in the Farnsworth-Munsell 100-Hue test, arising from the
      grouping of the caps into four boxes, was investigated. The traditional method of
      scoring performed with the numbers of the anchor caps disregarded and the
      alternative scoring performed with the numbers of the anchor caps employed, were
      compared. For the traditional method of scoring, we revealed an increase of the
      error score of the outside (end-box) caps when the total error score was above
      240. On the contrary for scoring performed with the numbers of the anchor caps
      employed, the difference between the error score of the outside caps and the
      average error per cap is not significant. To mitigate the end-box artefact and to
      improve the reliability of the Farnsworth-Munsell 100-Hue test, corrections to
      the traditional method of scoring are proposed.

PMID- 17040423
TI  - Subtle binocular vision anomalies in migraine.
AB  - A literature review reveals old references to an association between migraine
      headache and binocular vision anomalies, but a lack of scientific evidence
      evaluating these claims. In a masked case control study, we investigated
      binocular vision using standard clinical tests in people with migraine and in
      controls. Some test results suggest that heterophoria and fixation disparity are
      more common in the migraine group. The migraine group also had slightly reduced
      stereopsis. We found significant correlations between some migraine variables and
      some binocular vision variables (e.g., duration of worst headache and impaired
      stereopsis) but our analyses do not suggest that a causal relationship is likely.
      In conclusion, people with migraine have on average a slightly higher prevalence
      of heterophoria and aligning prism, and reduced stereopsis compared with
      controls. However, the differences are subtle and our data do not support the use
      of binocular vision interventions prescribed solely on the basis of the presence
      of migraine.

PMID- 17040424
TI  - Comparison of logMAR ETDRS chart and a new computerised staircased procedure for
      assessment of the visual acuity of children.
AB  - The validity and repeatability of visual acuity measures are particularly
      important in the detection and monitoring of childhood visual anomalies such as
      amblyopia. The repeatability and sensitivity of a new computerised visual acuity
      test, 'Staircased Procedure' is compared with the now gold standard visual acuity
      test, the early treatment of diabetic retinopathy study (ETDRS). Twenty-seven
      visually normal children (mean age: 6.7 +/- 1.1 years) and 27 children with
      amblyopia (mean age: 6.1 +/- 0.7 years) were tested with the ETDRS and Staircased
      Procedure. A retest was administered 4-5 weeks later and 30 min later for the
      visually normal and the amblyopic children, respectively. The staircased
      procedure produced significantly better visual acuity than the ETDRS for visually
      normal and amblyopic children. Repeatability was similar for both tests (ETDRS:
      0.11 log units; staircased procedure: 0.13 log units). In conclusion, the
      Staircased Procedure was an acceptable test with high repeatability and validity.

PMID- 17040425
TI  - Approximating ocular surfaces by generalised conic curves.
AB  - Most of the optical models of the human eye use simple conic functions to
      represent its individual components such as corneal surfaces and the surfaces of
      the crystalline lens. Although a conic function provides an acceptable
      approximation for most anatomical eye surfaces, it also leads to a simple optical
      analysis of the whole eye system. To fill the gap between the classical use of
      conic surfaces and the use of more sophisticated functions that often invoke
      numerically expensive procedures in the optical analysis, a functional
      generalisation of the conic curve is proposed. A detailed derivation of the
      generalised conic function is presented for a two-dimensional (meridional) case.
      This is followed by a three-dimensional surface approximation. Examples are given
      in which the superiority of the proposed approximation over a classical conic
      function as well as the hyperbolic cosine approximation is evident. In
      particular, it is shown that for an average total corneal profile, the proposed
      generalisation results in a residual height error that is of an order smaller
      than those achieved with the conic and hyperbolic cosine approximations. In
      conclusion, the proposed generalised conic function can be a useful tool in eye
      modelling, where the simplicity of expression is often desirable.

PMID- 17040427
TI  - Rituximab: applications in dermatology.
AB  - Rituximab is a chimeric anti-CD20 monoclonal antibody which has been used
      extensively for B-lymphocytic malignancies. In addition, applications for
      autoimmune diseases have emerged in recent years. Case reports support the use of
      rituximab in certain dermatologic conditions, including paraneoplastic pemphigus,
      pemphigus vulgaris, graft versus host disease, and cutaneous B-cell malignancies.
      Clinical trials are lacking and would be an appropriate next step.

PMID- 17040428
TI  - Serum eosinophil cationic protein in children with atopic dermatitis.
AB  - BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by
      activated eosinophils during allergic and inflammatory processes. The aim of the
      study was to determine the ECP level, absolute and relative eosinophil count and
      IgE antibodies in children with atopic dermatitis (AD) compared with those of
      nonatopic children, and to assess the correlation of these laboratory parameters
      with the clinical severity of AD. METHODS: This prospective study comprised 70
      children. There were 49 children with AD aged 3-36 months, and the control group
      comprised 21 children with a negative personal and family history for atopic
      diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute
      eosinophil counts and total serum IgE antibodies were determined in both groups.
      In the children with AD, skin involvement was measured by the SCORAD index.
      RESULTS: The calculated SCORAD index was between 16 and 83. IgE antibodies,
      relative and absolute eosinophil counts showed a significantly wider range of
      values and a statistically higher median (P < 0.001) in the patients with AD
      compared with the control group. These laboratory parameters did not correlate
      with the severity of AD. The serum ECP median level, in the children with AD, was
      16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90)
      in the control group. Correlation of the total SCORAD index and the serum ECP
      levels was negative, weak (r = -0.065) and statistically not significant (P >
      0.05). The same was found for the correlation of serum ECP and intensity of skin
      changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The
      correlation was positive, but weak and statistically not significant for the
      serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). CONCLUSION:
      Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE
      antibodies were determined in the patients with AD. As these laboratory findings
      did not correlate with the severity of AD, they can be considered only as
      additional methods in the evaluation of patients with AD.

PMID- 17040429
TI  - Self-inflicted garlic burns: our experience and literature review.
AB  - BACKGROUND: Throughout history, garlic has been used to treat a large variety of
      illnesses. One of garlic's adverse local effects is contact dermatitis. METHODS:
      We present three patients treated in the Department of Plastic Surgery for
      suspected self-inflicted lower extremity burns. RESULTS: The burns had unique
      features, not consistent with the etiology first claimed by the patients. All
      were soldiers with low motivation who confessed to using garlic to cause the
      burns. CONCLUSIONS: Garlic application usually results in local inflammation,
      but, if applied under a pressure bandage, or if there is poor wound care or a
      secondary infection, it can cause a severe dermal reaction and a deep chemical
      burn. We present these cases to increase physician awareness of the
      characteristics of self-inflicted garlic burns, and review the dermatotoxic
      effect.

PMID- 17040430
TI  - Prurigo pigmentosa: not an uncommon disease in the Turkish population.
AB  - BACKGROUND: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis of unknown
      etiology. It is characterized by erythematous papules of the trunk that resolve
      leaving a reticulate hyperpigmentation. The original report from Japan in 1971
      was followed by new cases, mostly of Japanese origin. METHODS: We scrutinized PP
      cases diagnosed in our clinic and reviewed the English, German, French, and
      Turkish language literature. RESULTS: We report six additional Turkish patients.
      We found more than 40 cases reported from various countries outside Japan. The
      patients had different racial origins. The number of Turkish patients reported in
      recent years is higher than the number of other non-Japanese patients reported.
      CONCLUSIONS: The disease is not uncommon in the Turkish population. It may be
      underestimated in other countries with Caucasian populations. Therapeutic results
      with tetracycline and doxycycline was successful in our patients.

PMID- 17040431
TI  - Evaluation of specific antibodies for early diagnosis and management of syphilis.
AB  - For many years, tests for cardiolipin antibodies Tp15, Tp17, Tp45, Tp47, and
      other specific Treponema pallidum antibodies, have been used to diagnose
      syphilis, but the timing and rates of antibody detection differ in primary and
      secondary syphilis. Our objective was to determine the value of the rapid plasma
      reagin (RPR) test, T. pallidum passive particle agglutination (TPPA) assay and
      Western blotting (WB) in the diagnosis of early syphilis, by studying 67 patients
      (20 with primary and 47 with secondary syphilis) over a recent 5-year period. All
      patients were tested before and 21/67 were tested after treatment. Western
      blotting showed that while there was a difference within the study group in terms
      of the number of bands detected, all patients with primary syphilis demonstrated
      the 47-kDa antibody, but RPR and TPPA were negative in some patients. Eighteen to
      24 months after treatment, 21/67 patients were tested by WB and TPPA; antibodies
      to T. pallidum became undetectable within 24 months after treatment in 29% of
      patients. By RPR, 29% patients had negative titers within 6 months of treatment,
      and 86% returned to normal within 24 months. We conclude that detection of
      specific 47-kDa T. pallidum antibodies can be used to diagnose primary syphilis.
      By RPR, antibodies disappear in 6-24 months after treatment in many patients,
      suggesting that a change in titer may be an indicator of treatment success.

PMID- 17040432
TI  - Unusual palmoplantar blistering in the setting of hemodialysis: a case report and
      review of the dermatoses associated with hemodialysis.
AB  - We describe a 70-year-old White female on maintenance high-flux hemodialysis for
      chronic renal insufficiency with an abrupt onset of asymptomatic palmoplantar
      blisters. The lesions were tense, noninflamed and 0.2-1.0 cm in dimension.
      Concomitant photo-distributed blistering of the dorsal hands and forearms was not
      present. A cutaneous biopsy demonstrated nonspecific histological and direct
      immunofluorescent findings. Serum indirect immunofluorescence and tissue cultures
      for bacteria, fungi and viruses were negative. Fecal porphyrins were normal but
      an elevated plasma uroporphyrin level of 17.0 microg/dL (normal: < 1.0 microg/dL)
      was observed. The duration of each hemodialysis treatment, which the patient had
      continued to receive three times per week, was changed from 2 to 2.5 h. Within 2
      weeks no new blisters occurred. Within 6 weeks complete clinical and biochemical
      remission was noted. During this time course no topical steroid or antifungal
      therapy was employed nor was the patient's oral medication regimen altered.

PMID- 17040433
TI  - Genetic epidemiology of vitiligo: a study of 815 probands and their families from
      south China.
AB  - BACKGROUND: Genetic factors are thought to be involved in the development of
      vitiligo. AIM: To explore the possible genetic model of vitiligo by analyzing the
      genetic characteristics of 815 patients and their families from south China
      (Zhejiang Province). METHODS: Data for 815 patients with vitiligo were obtained
      by questionnaire. The inheritance pattern estimation, heritability calculation,
      and complex segregation analysis were performed using the Penrose method,
      Falconer regression method, and SAGE-REGTL program, respectively. RESULTS: In 815
      vitiligo probands, 128 (15.7%) had a family history. The ratio of the sibling
      prevalence rate to the population prevalence rate (s/q) approached 1/square root
      q using the Penrose calculation, and the heritability degrees of vitiligo in the
      first- and second-degree relatives were 59.6% and 55.2%, respectively. The
      complex segregation analysis suggested that the dominant model was the best-fit
      genetic model for vitiligo. CONCLUSIONS: Genetic factors play an important role
      in the occurrence of vitiligo, and the genetic model of vitiligo in this
      population is consistent with a polygenetic or multifactorial inheritance in a
      dominant major gene pattern.

PMID- 17040434
TI  - Erosive pustular dermatosis of the leg.

PMID- 17040435
TI  - Association of linear IgA bullous disease of childhood with Crohn's disease.

PMID- 17040436
TI  - Central trichoptilosis with onycholysis.

PMID- 17040437
TI  - Monosymptomatic hypochondriacal psychosis presenting with recurrent oral mucosal
      ulcers and multiple skin lesions responding to olanzapine treatment.
AB  - Monosymptomatic hypochondriacal psychosis (MHP) is a form of psychosis
      characterized by the delusional idea that there is a serious problem in the skin
      or other body parts. Because MHP patients believe that their complaint is
      dermatological, not psychiatric, they often admit to several other medical
      disciplines before coming to a psychiatry clinic. This leads to a series of time
      consuming examinations and treatment interventions. In this case report, we
      emphasize the importance of diagnosing the illness correctly and referring the
      patient to a psychiatrist. The patient presented in this report has been treated
      with a new generation neuroleptic, olanzapine. This treatment has led to complete
      resolution of delusional symptoms. Therefore, we conclude that knowing that MHP
      is a psychiatric illness allows early establishment of diagnosis and successful
      treatment.

PMID- 17040438
TI  - CD4/CD8 double-positive, acute type of adult T-cell leukemia/lymphoma with
      extensive cutaneous involvement.

PMID- 17040439
TI  - Trichotillomania or alopecia areata?

PMID- 17040440
TI  - Unusual coexistence of molluscum contagiosum and verruca plana in a hyper-IgE
      syndrome.

PMID- 17040441
TI  - Precalcaneal congenital fibrolipomatous hamartoma.

PMID- 17040442
TI  - Cutaneous and pulmonary nocardiosis in pemphigus vulgaris: a rare complication of
      immunosuppressive therapy.

PMID- 17040443
TI  - Primary amelanotic melanoma of the esophagus.
AB  - Primary melanoma of the esophagus (PME) is an uncommon malignancy with less than
      250 cases reported in the literature. Amelanotic PME is exceedingly rare and
      accounts for 10-25% of melanomas of the esophagus. A 59-year-old male with a
      history of mild dysphagia, heartburn, moderate anorexia and weight loss for 1
      month is described. Barium swallow examination and videogastroscopy showed a
      polypoid, ulcerated mass located 30-38 cm from the incisors. No skin or eye
      melanoma lesions were found. Five biopsy samples were obtained. Histological
      examinations revealed proliferation of large, loosely cohesive cells of variable
      shapes and prominent central nucleoli in the deep mucosa. Immunohistochemical
      findings included positive vimentin, protein S-100, Melan A, and HMB-45, and
      negative AE1/AE3, CD 17, and desmin. A total transhiatal esophagectomy with high
      cervical esophagogastric anastomosis was performed. Peritumoral lymph nodes
      revealed malignant invasion. A diagnosis of primary amelanotic melanoma of the
      esophagus was made. Fourteen months after diagnosis the patient developed
      disseminated PME.

PMID- 17040444
TI  - Angiolymphoid hyperplasia with eosinophilia induced by trauma.

PMID- 17040445
TI  - Unusual cutaneous findings of urticaria pigmentosa and telangiectasia macularis
      eruptiva perstans associated with marked myelofibrosis.
AB  - Mastocytosis is a heterogeneous group of disorders characterized by mast cell
      hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal
      tract, and skin. We present a patient with malignant mastocytosis of 11 years'
      duration. This case highlights the cutaneous findings of mastocytosis with
      systemic involvement, yet the patient maintains a relatively normal lifestyle
      with only minimal discomfort and only borderline normochromic anemia. Thus his
      course is not truly that of malignant mastocytosis but of indolent systemic
      mastocytosis with cutaneous findings of telangiectasia macularis eruptiva
      perstans (TMEP).

PMID- 17040446
TI  - Syringoid eccrine carcinoma with apparently aggressive transformation: case
      report and review of the literature.

PMID- 17040447
TI  - Necrotizing fasciitis: delay in diagnosis results in loss of limb.

PMID- 17040448
TI  - Treatment of severe chronic idiopathic urticaria with oral mycophenolate mofetil
      in patients not responding to antihistamines and/or corticosteroids.
AB  - BACKGROUND: Urticarial patients are usually treated with oral antihistamines and
      50% respond well to this treatment; however, the other 50% do not respond to
      antihistamines and need a more aggressive approach, such as short or prolonged
      courses of oral corticosteroids or cyclosporine. Potential adverse effects,
      however, limit this regimen. OBJECTIVE: To determine the efficacy of
      mycophenolate mofetil, an immunomodulatory drug, in the treatment of patients
      with severe chronic urticaria. METHODS: In an open-label, uncontrolled trial,
      nine patients with documented chronic urticaria who had been treated previously
      with antihistamines and/or corticosteroids with poor response were enrolled in
      the trial. After 2 weeks of baseline assessment, patients received 1000 mg twice
      daily of mycophenolate mofetil for 12 weeks. Improvement was monitored using the
      urticarial activity score, which is the sum of the wheal number score and itch
      severity score. Patients also recorded their daily need for other medications to
      control allergic symptoms. RESULTS: There was a significant decrease in the
      urticarial activity score relative to the baseline assessment at the end of the
      study period (P < 0.001). All patients were able to stop prednisone on completion
      of the study. There was also a decrease in antihistamine dose, but this did not
      reach statistical significance. Treatment with mycophenolate mofetil was not
      associated with significant adverse effects. CONCLUSIONS: Mycophenolate mofetil
      may be a valuable and safe treatment for patients with chronic urticaria who do
      not respond to antihistamines and/or corticosteroids, and who require aggressive
      treatment to control their disease symptoms. Further controlled clinical studies
      are needed to determine its value.

PMID- 17040449
TI  - Contribution of Brazilian dermatologists to the development of dermatology.

PMID- 17040450
TI  - Public health dermatology: regeneration and repair of the skin in the developed
      transitional and developing world.

PMID- 17040451
TI  - Efficacy of isotretinoin in pityriasis rubra pilaris: unapproved use.

PMID- 17040452
TI  - Irritant-induced enhancement of induction and elicitation of sensitization for
      the treatment of seborrheic keratoses.

PMID- 17040453
TI  - Subjective and objective measurement methods in clinical dermatology from an
      historical perspective: the long way from Joseph Plenck to validation.

PMID- 17040454
TI  - Effective treatment of erosive lichen planus with thalidomide and topical
      tacrolimus.

PMID- 17040455
TI  - Tetracycline/doxycycline-induced cutaneous depressed pigmentation.

PMID- 17040456
TI  - Acute generalized exanthematous pustulosis triggered by intake of herbal
      medications.

PMID- 17040457
TI  - Heliotrope-like eruption mimicking dermatomyositis in a patient treated with
      imatinib mesylate for chronic myeloid leukemia.

PMID- 17040458
TI  - Successful treatment of Zoon's balanitis with topical tacrolimus.

PMID- 17040459
TI  - Vulvo-vaginal-gingival syndrome of lichen planus.

PMID- 17040460
TI  - Bullous Sweet's syndrome following influenza vaccination in a HIV-infected
      patient.

PMID- 17040461
TI  - Hydroxychloroquine as a treatment for atrophoderma of Pasini and Pierini.

PMID- 17040462
TI  - Cytokeratin 7 staining was useful in a case of pigmented mammary Paget's disease
      resembling malignant melanoma.

PMID- 17040463
TI  - Black piedra: report of a French case associated with Trichosporon asahii.

PMID- 17040464
TI  - Toxic epidermal necrolysis caused by tetrazepam.

PMID- 17040465
TI  - Chloroquine/hydroxychloroquine-induced pemphigus.

PMID- 17040466
TI  - Malignant eccrine poroma presenting with pulmonary and liver metastases.

PMID- 17040467
TI  - Treatment of HIV-associated eosinophilic pustular folliculitis with narrow-band
      UVB.

PMID- 17040468
TI  - Cutaneous schwannoma treated by tumescent suction technique.

PMID- 17040469
TI  - Unilesional folliculotropic/syringotropic cutaneous T-cell lymphoma presenting as
      an indurated plaque on the nape.

PMID- 17040470
TI  - Evaluation of a pharmacotherapy context-learning programme for preclinical
      medical students.
AB  - AIM: To evaluate a context-learning pharmacotherapy programme for approximately
      750 2nd, 3rd and 4th year preclinical medical students with respect to mastering
      cognitive pharmacotherapeutic skills, i.e. choosing a (drug) treatment and
      determining patient information. METHODS: The context-learning pharmacotherapy
      programme consists of weekly organized role play sessions in the form of
      consulting hours. Fourth year students sit for a therapeutic Objective Structured
      Clinical Examination (OSCE) in the form of consulting hours at the outpatient
      clinic. Sixty-one 2nd, 74 3rd and 49 4th year medical students who attended the
      role play sessions and the OSCE were randomly selected. Their performances were
      assessed by clinical examiners and clinical experts and compared with a reference
      group of 6th year graduated students. Additionally, the scores of a questionnaire
      on study load and appreciation were collected. RESULTS: The level of the
      pharmacotherapeutic skills of the 4th year students who followed the
      pharmacotherapy context-learning programme was not far below that of 6th year
      graduates who had finished their clinical clerkships, but had not followed the
      pharmacotherapy programme. The time spent on the programme was about 1% of the
      total study load per year. The students appreciated the role play sessions and
      OSCE by around 80% and 99% of the maximum possible scores. CONCLUSIONS:
      Preclinical pharmacotherapy context learning has a modest but positive effect on
      learning cognitive pharmacotherapeutic skills, i.e. choosing a drug treatment and
      determining patient information. This effect has been obtained with role play
      sessions, a suboptimal form of context learning, with a minimal study load and a
      high appreciation by students.

PMID- 17040471
TI  - Relationship of opioid receptors with GABAergic neurons in the rat inferior
      colliculus.
AB  - The inferior colliculus is a critical structure for processing auditory
      information and receives ascending and descending synaptic auditory projections.
      In addition to GABAergic and glutamatergic innervations, other neurotransmitter
      systems are also reported in the inferior colliculus, including opioid peptides.
      In the present study, the relative distribution of each type of opioid receptor,
      mu (MOR), delta (DOR) and kappa (KOR) within GABAergic neurons in the inferior
      colliculus was examined. GABA immunoreactivity was expressed by small, medium and
      large neurons and distributed in the central nucleus and the pericentral nucleus
      of the inferior colliculus. Immunostaining for MOR, DOR and KOR receptors was
      found in both disc-shaped cells and stellate cells. Punctiform beta-endorphin
      immunolabelling was observed in the proximity of GABA-positive neurons. Co
      localization of GABA and MOR receptors was observed in neurons and nerve
      terminals in the central nucleus, dorsal cortex and external cortex of the
      inferior colliculus. Quantification of the co-localization patterns determined
      that a higher proportion of GABA neurons was associated with MOR receptors
      compared with KOR or DOR receptors.

PMID- 17040472
TI  - Effects of nitric oxide-active drugs on the discharge of subthalamic neurons:
      microiontophoretic evidence in the rat.
AB  - The presence of nitric oxide (NO) synthase and of soluble guanylyl cyclase, the
      main NO-activated metabolic pathway, has been demonstrated in many cells of the
      subthalamic nucleus. In this study, the effects induced on the firing of 96
      subthalamic neurons by microiontophoretically administering drugs modifying NO
      neurotransmission were explored in anaesthetized rats. Recorded neurons were
      classified into regularly and irregularly discharging on the basis of their
      firing pattern. Nomega-nitro-L-arginine methyl ester (L-NAME; a NO synthase
      inhibitor), 3-morpholino-sydnonimin-hydrocloride (SIN-1; a NO donor), S-nitroso
      glutathione (SNOG; another NO donor) and 8-Br-cGMP (a cell-permeable analogue of
      cGMP, the main second-messenger of NO neurotransmission) were iontophoretically
      applied while performing single-unit extracellular recordings. The activity of
      most neurons was influenced in a statistically significant way: in particular,
      both current-related inhibitory L-NAME-induced effects (20/39 tested cells) and
      excitatory effects of SIN-1 (25/41 tested neurons), SNOG (19/32 tested cells) and
      8-Br-cGMP (13/19 tested neurons) were demonstrated. Neither statistically
      significant differences between the responses of regularly and irregularly
      discharging cells, nor specific topographical clustering of responding neurons,
      were demonstrated. Neurons administered drugs oppositely modulating the NO
      neurotransmission often displayed responses to only one treatment. We hypothesize
      that NO neurotransmission could exert a modulatory influence upon subthalamic
      neurons, with a prevalent excitatory effect. However, in the light of the
      presence of some responses of opposite sign to the same drug displayed by
      different subthalamic neurons, more complex effects of NO neurotransmission could
      be suggested, probably due to interactions with other classical neurotransmitter
      systems.

PMID- 17040473
TI  - Neuropathic pain and the endocannabinoid system in the dorsal raphe:
      pharmacological treatment and interactions with the serotonergic system.
AB  - We used a model of neuropathic pain consisting of rats with chronic constriction
      injury (CCI) of the sciatic nerve, in order to investigate whether
      endocannabinoid levels are altered in the dorsal raphe (DR) and to assess the
      effect of repeated treatment with (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate, a synthetic cannabinoid agonist, or N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z
      eicosatetraenamide (AM404), an inhibitor of endocannabinoid reuptake, on DR
      serotonergic neuronal activity and on behavioural hyperalgesia. CCI resulted in
      significantly elevated anandamide but not 2-arachidonoylglycerol levels in the
      DR. Furthermore, as well as thermal and mechanical hyperalgesia, CCI caused
      serotonergic hyperactivity (as shown by the increase of basal activity of
      serotonergic neurones, extracellular serotonin levels and expression of 5-HT1A
      receptor gene). Repeated treatment with either (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate or AM404 reverted the hyperalgesia and enhanced serotonergic activity
      induced by CCI in a way attenuated by N-piperidino-5-(4-chlorophenyl)-1
      (2,4dichlorophenyl)-4-methyl-3-pyrazolecarboxamide, a selective cannabinoid
      subtype 1 (CB1) receptor antagonist. Despite the elevated levels of anandamide
      following CCI, N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3
      pyrazolecarboxamide did not produce hyperalgesia or any other effect on
      serotonergic neuronal activity when administered alone. Furthermore, the effects
      of AM404 were not accompanied by an increase in endocannabinoid levels in the DR.
      In conclusion, following CCI of the sciatic nerve, the endocannabinoid and
      serotonergic systems are activated in the DR, where repeated stimulation of CB1
      receptors with exogenous compounds restores DR serotonergic activity, as well as
      thermal and mechanical nociceptive thresholds, to pre-surgery levels. However, an
      elevated level of endogenous anandamide in the DR does not necessarily contribute
      to the CB1-mediated tonic control of analgesia and serotonergic neuronal
      activity.

PMID- 17040474
TI  - Activation of muscarinic cholinergic receptors inhibits giant neurones in the
      caudal pontine reticular nucleus.
AB  - Giant neurones in the caudal pontine reticular nucleus (PnC) play a crucial role
      in mediating the mammalian startle response. They receive input from cochlear,
      trigeminal and vestibular nuclei and project directly to motoneurones.
      Furthermore, they integrate modulatory input from different brain regions either
      enhancing or inhibiting startle responses. One prominent startle modulation is
      prepulse inhibition where a non-startling stimulus presented prior to the startle
      stimulus inhibits a subsequent startle response. Several behavioural studies have
      indicated that this inhibition is mediated by muscarinic receptors at the level
      of the PnC. Here, we performed whole-cell patch-clamp recordings from PnC giant
      neurones in acute rat brain slices in order to examine muscarinic inhibition. We
      stimulated afferent trigeminal and auditory fibres and applied muscarinic
      agonists and antagonists in order to investigate their effect on excitatory
      postsynaptic current amplitudes, paired-pulse ratio and passive membrane
      properties of PnC giant neurones. The cholinergic agonist carbachol and the
      muscarinic agonist oxotremorine significantly reduced excitatory postsynaptic
      current amplitudes and increased the paired-pulse ratio. Carbachol additionally
      reduced the membrane resistance of postsynaptic PnC giant neurones. The subtype
      specific antagonists AF-DX116 (M2 preferring) and tropicamide (M4 preferring)
      antagonized the oxotremorine effect indicating that M4 and possibly M2 receptor
      subtypes are involved in this inhibition. The G-protein-activated inward
      rectifying potassium channel blocker tertiapin-Q had no effect on oxotremorine
      induced inhibition of giant neurones. Our results show a mainly presynaptically
      mediated strong inhibition of PnC giant neurones by activation of M4 and possibly
      M2 receptors that presumably contribute to prepulse inhibition.

PMID- 17040475
TI  - Striatum gray matter reduction in males with an overactive behavioral activation
      system.
AB  - Using optimized voxel-based morphometry, we studied the relationship between gray
      matter volume in brain areas associated with reward and scores on a behavioral
      activation system measure (the Sensitivity to Reward scale) in a sample of 50
      male undergraduates. Voxel-based morphometry analysis revealed a negative
      correlation between Sensitivity to Reward scores and gray matter volume in the
      dorsal striatum and prefrontal cortex. Results indicate that a reduced volume in
      the striatum might be associated with enhanced reward sensitivity and deficits in
      inhibitory control.

PMID- 17040476
TI  - Neurosteroid pregnenolone sulfate enhances glutamatergic synaptic transmission by
      facilitating presynaptic calcium currents at the calyx of Held of immature rats.
AB  - Pregnenolone sulfate (PREGS) is an endogenous neurosteroid widely released from
      neurons in the brain, and is thought to play a memory-enhancing role. At
      excitatory synapses PREGS facilitates transmitter release, but the underlying
      mechanism is not known. We addressed this issue at the calyx of Held in rat
      brainstem slices, where direct whole-cell recordings from giant nerve terminals
      are feasible. PREGS potentiated nerve-evoked excitatory postsynaptic currents
      (EPSCs) without affecting the amplitude of miniature EPSCs, suggesting that its
      site of action is presynaptic. In whole-cell recordings from calyceal nerve
      terminals, PREGS facilitated Ca2+ currents, by accelerating their activation
      kinetics and shifting the half-activation voltage toward negative potentials.
      PREGS had no effect on presynaptic K+ currents, resting conductance or action
      potential waveforms. In simultaneous pre- and postsynaptic recordings, PREGS did
      not change the relationship between presynaptic Ca2+ influx and EPSCs, suggesting
      that exocytotic machinery downstream of Ca2+ influx is not involved in its
      effect. PREGS facilitated Ba2+ currents recorded from nerve terminals and also
      from HEK 293 cells expressed with recombinant N- or P/Q-type Ca2+ channels,
      suggesting that PREGS-induced facilitation of voltage-gated Ca2+ channels (VGCCs)
      is neither Ca2+ dependent nor VGCC-type specific. The PREGS-induced VGCC
      facilitation was blocked by the PREGS scavenger (2-hydroxypropyl)-beta
      cyclodextrin applied from outside, but not from inside, of nerve terminals. We
      conclude that PREGS facilitates VGCCs in presynaptic terminals by acting from
      outside, thereby enhancing transmitter release. We propose that PREGS may
      directly modulate VGCCs acting on their extracellular domain.

PMID- 17040477
TI  - Locomotor activity correlates with modifications of hippocampal mossy fibre
      synaptic transmission.
AB  - The hippocampus has long been implicated in memory formation. Although
      accumulating evidence suggests involvement of the hippocampus in other brain
      functions including locomotor regulation and emotional processes, cellular and
      synaptic bases underlying these functions remain largely unknown. We here report
      that environmental manipulations in mice unveiled the association of locomotor
      activity with the hippocampal mossy fibre (MF) synaptic transmission.
      Electrophysiological recordings of synaptic responses were made using hippocampal
      slices prepared from mice whose behaviour had been analysed. Environmental
      enrichment induced parallel decreases in open-field locomotor activity and MF
      synaptic facilitation. Facilitation induced by paired-pulse stimulation at
      relatively long intervals (>or=200 ms) was selectively reduced while the basal
      synaptic efficacy and high-frequency transmission were unaffected. Social
      isolation caused a change in behaviour in an elevated plus-maze, but neither the
      open-field activity nor the MF synaptic transmission was significantly altered.
      Effects of dopamine, a neurotransmitter essential for locomotor regulation, on
      the MF synapse were also examined using these mice. Environmental manipulations
      did not cause significant changes in potentiation of the MF synaptic transmission
      induced by dopamine. However, analysis of behavioural and electrophysiological
      results in individual subjects revealed that locomotor activity negatively
      correlates with magnitude of the dopamine-induced potentiation. These results
      suggest that the MF synapse plays important roles in the regulation of locomotor
      activity. We propose that the MF synapse can serve as the synaptic model for
      certain forms of locomotor regulation, with potential importance for
      investigation of the pathophysiology of psychiatric diseases using animal models.

PMID- 17040478
TI  - Injury-induced axonal sprouting in the hippocampus is initiated by activation of
      trkB receptors.
AB  - Penetrating head injuries are often accompanied by the delayed development of
      post-traumatic epilepsy. Schaffer collateral transection leads to axonal
      sprouting and hyperexcitability in area CA3 of hippocampal slice cultures. We
      used this model to test the hypothesis that the injury-induced axonal sprouting
      results from increased neurotrophin signaling via trkB receptors near the lesion.
      Using rats and mice, we established that sprouting CA3 pyramidal cell axons are
      labeled with an antibody to the growth-associated protein GAP-43. We observed two
      to threefold increases in the level of brain-derived neurotrophic factor and
      trkB protein in area CA3 by 24-48 h after Schaffer collateral transection,
      preceding the onset of axonal sprouting. Finally, we demonstrated that injury
      induced axonal sprouting of GAP-43-immunoreactive axons is impaired in
      hippocampal slice cultures from mice expressing low levels of trkB receptors. We
      conclude that injury-induced axonal sprouting is initiated by brain-derived
      neurotrophic factor-trkB signaling and suggest that this process may be critical
      for the genesis of post-traumatic epilepsy.

PMID- 17040479
TI  - Mechanisms involved in modulation of trigeminal primary afferent activity in rats
      with peripheral mononeuropathy.
AB  - In order to clarify the mechanisms underlying the changes in primary afferent
      neurons in trigeminal neuropathic pain, a chronic constriction nerve injury model
      of the infraorbital nerve (ION-CCI) was developed in rats. Mechanical allodynia
      was observed at 3 days after ION-CCI and lasted more than 14 days. Single-unit
      activities were recorded from the ION of anesthetized rats. C-, Abeta- and Adelta
      units were identified on the basis of their conduction velocity. Adelta-units
      were frequently encountered at a later period after ION-CCI. The highest Adelta
      spontaneous activity was recorded at 3 days after ION-CCI and progressively
      decreased after that, but spontaneous activity was still higher at 14 days after
      ION-CCI than that of naive rats. Mechanical-evoked responses of Adelta-units were
      also highest at 3 days after ION-CCI and then gradually decreased. In
      consideration of these data, patch-clamp recordings were performed on medium to
      large size neurons of the dissociated trigeminal ganglion (TRG). Patch-clamp
      recordings revealed that the IK (sustained) and IA (transient) in rats with ION
      CCI were significantly smaller than those of naive rats, and correlated with an
      increase in duration of repolarization phase and a decrease in duration of
      depolarization phase, respectively. The hyperpolarization-activated current (Ih)
      was significantly larger in TRG neurons of rats with ION-CCI as compared with
      those of naive rats. The present results suggest that Ih, IK and IA in Adelta
      afferent neurons in TRG are significantly involved in the changes in afferent
      spontaneous activity and mechanically evoked activity that accompany mechanical
      allodynia produced by trigeminal nerve injury.

PMID- 17040480
TI  - Increased expression and activity of urokinase-type plasminogen activator during
      epileptogenesis.
AB  - Our recent large-scale molecular profiling study revealed a sevenfold
      upregulation in the expression of urokinase-type plasminogen activator (uPA)
      during epileptogenesis. uPA is a member of the plasminogen activation system,
      which is a major contributor to the reorganization of neuronal circuits after
      trauma. Here, we investigated the expression and activity of uPA in normal and
      epileptogenic rat hippocampus to test a hypothesis that the expression of uPA is
      altered in brain areas that undergo epilepsy-related circuitry reorganization.
      Epileptogenesis was triggered by inducing status epilepticus (SE) with electrical
      stimulation of the amygdala in rats. Continuous video-electroencephalogram
      recordings were used to monitor the development of SE and the occurrence of
      spontaneous seizures. Animals were killed at 1, 4 or 14 days after SE, and brains
      were processed for immunohistochemistry or protein extraction. Confocal
      microscopy analysis of double-immunolabelled preparations indicated that SE
      triggered an increased expression of uPA in hippocampal astrocytes, neurons,
      white matter and blood vessels. Zymography revealed that the expression of uPA
      protein is associated with increased levels of enzymatically active uPA during
      epileptogenesis. uPA expression and enzymatic activity peaked within 1-4 days
      after SE, that is, before the occurrence of spontaneous seizures, and remained
      elevated for at least 2 weeks. These data suggest that uPA is involved in the
      reorganization of neuronal tissue during the epileptogenic process.

PMID- 17040481
TI  - Brain-derived neurotrophic factor (BDNF) is required for the enhancement of
      hippocampal neurogenesis following environmental enrichment.
AB  - Neurogenesis continues to occur in the adult mammalian hippocampus and is
      regulated by both genetic and environmental factors. It is known that exposure to
      an enriched environment enhances the number of newly generated neurons in the
      dentate gyrus. However, the mechanisms by which enriched housing produces these
      effects are poorly understood. To test a role for neurotrophins, we used
      heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and
      mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates.
      Mice were either reared in standard laboratory conditions or placed in an
      enriched environment for 8 weeks. Animals received injections of the mitotic
      marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and
      enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as
      assessed by stereological counting of BrdU-positive cells in the dentate gyrus
      and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this
      enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice.
      Failure to up-regulate BDNF accompanied the lack of a neurogenic response in
      enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required
      for the environmental induction of neurogenesis.

PMID- 17040482
TI  - Biodiversity of Saccharomyces yeast strains from grape berries of wine-producing
      areas using starter commercial yeasts.
AB  - The use of commercial wine yeast strains as starters has grown extensively over
      the past two decades. In this study, a large-scale sampling plan was devised over
      a period of 3 years in three different vineyards in the south of France, to
      evaluate autochthonous wine yeast biodiversity in vineyards around wineries where
      active dry yeasts have been used as fermentation starters for more than 5 years.
      Seventy-two spontaneous fermentations were completed from a total of 106 grape
      samples, and 2160 colonies were isolated. Among these, 608 Saccharomyces strains
      were identified and 104 different chromosomal patterns found. The large majority
      of these (91) were found as unique patterns, indicating great biodiversity. There
      were differences in biodiversity according to the vineyard and year, showing that
      the biodiversity of Saccharomyces strains is influenced by climatic conditions
      and specific factors associated with the vineyards, such as age and size. Strains
      that were terroir yeast candidates were not found. The biodiversity of S.
      cerevisiae strains after harvest was similar to that in the early campaign;
      moreover, a temporal succession of S. cerevisiae strains is shown. This fact,
      together with the differences in biodiversity levels verifies that other factors
      were more important than commercial yeast utilization in the biodiversity of the
      vineyard.

PMID- 17040483
TI  - Study design, recruitment, and baseline characteristics: the Department of
      Veterans Affairs Dental Diabetes Study.
AB  - OBJECTIVES: We are conducting a clinical trial of the efficacy of periodontal
      therapy in the improvement of glycaemic control in veterans with poorly
      controlled diabetes. This report describes study design, recruitment and
      randomization and compares baseline characteristics of the sample frame with
      those randomized into study groups. METHODS: Veterans with poorly controlled
      diabetes were randomized in two groups: immediate periodontal therapy ("early
      treatment") or usual care followed by periodontal therapy ("deferred treatment").
      Half of each group continued care for 12 months; the other half returned to their
      usual care. We studied baseline patient characteristics, self-reported health
      measures, and clinical examination data. We examined means for continuous
      variables, frequencies for categorical variables and compared groups using t
      tests and chi(2) tests (alpha=0.05 for both). RESULTS: The 193 randomized
      participants were younger (58 years) and had slightly higher HbA1c (10.2%) than
      the 2534 non-randomized participants (64 years, HbA1c =9.8%). The deferred
      treatment group was more likely than the early treatment group to have a history
      of stroke, transient ischaemic attacks, and less likely to be current or former
      smokers. CONCLUSIONS: The mechanism for randomization was largely successful in
      this study.

PMID- 17040485
TI  - Endoplasmic reticulum and Golgi complex: Contributions to, and turnover by,
      autophagy.
AB  - The degradation of cytoplasmic contents, especially organelles [mitochondria,
      peroxisomes, endoplasmic reticulum (ER), Golgi complex (GC)], cannot be
      accomplished solely by the cytosolic degradation machinery, of which the most
      prominent component is the proteasome. However, it is possible that such
      organelles (or portions thereof) can be degraded by the cell's autophagic
      machinery. In this manner, organelles can be either specifically or non
      specifically targeted to the vacuole/lysosome for degradation. These processes
      can be triggered in response to different environmental cues. Here, we focus on
      two particular organelles, the ER and the GC, and their relationship with the
      autophagic process. Firstly, we briefly consider how these two organelles
      contribute to the synthesis and delivery of hydrolytic enzymes involved in
      autophagy as well as how they may potentially contribute to their own degradation
      by addressing the origin of the autophagic membrane. Secondly, we summarize the
      evidence for the turnover of these two organelles by autophagic processes in
      different organisms.

PMID- 17040484
TI  - An efficacy and safety analysis of a chlorhexidine chewing gum in young
      orthodontic patients.
AB  - AIM: The objective of the present study was to investigate the impact of a
      chlorhexidine (CHX) chewing gum in teenage orthodontic patients on plaque levels,
      gingival bleeding tendency and tooth staining. MATERIALS AND METHODS: A
      randomized-controlled, double-blind, parallel study was conducted on 31 teenagers
      in fixed orthodontic therapy. Subjects of the CHX gum group were asked to
      continue their oral hygiene procedures in conjunction with chewing two pieces of
      a 5 mg CHX-containing chewing gum for 10 min. twice a day for 3 months. Subjects
      of the placebo gum group received the same instructions; however, using a CHX
      free chewing gum. Plaque levels, gingival bleeding on probing and tooth staining
      were monitored at baseline and subsequently after 1-3 months. RESULTS: Plaque
      levels significantly decreased from baseline at lingual/palatal sites in the
      placebo gum group. In the CHX gum group, a similar, yet non-significant trend was
      observed. At buccal sites, plaque levels remained unaffected in both groups.
      Gingival bleeding tendency significantly decreased in both groups, predominantly
      at lingual/palatal sites. There were no significant between-group differences in
      any of the efficacy parameters at any time point. However, the increase in
      staining was nearly five times higher in the CHX gum group. CONCLUSIONS: There
      seems to be no indication for a CHX chewing gum in teenage orthodontic patients
      when used as an adjunct to normal oral hygiene practices.

PMID- 17040486
TI  - The prevalence of sexual dysfunction and potential risk factors that may impair
      sexual function in Malaysian women.
AB  - INTRODUCTION: Female sexual dysfunction (FSD) is a prevalent sexual health
      problem that does not spare the women in Malaysia, a nation with a conservative
      multiethnic society. AIM: To investigate the prevalence of FSD and the potential
      risk factors that may impair sexual function among women at a primary care
      setting in Malaysia. MAIN OUTCOME MEASURE: The prevalence, the risk factors, and
      the main predictors for FSD were measured among these women. METHODS: A validated
      Malay version of the Female Sexual Function Index was used to assess FSD. A total
      of 230 married women aged 18-70 years participated in this study. The
      sociodemographic and marital profiles of women who had FSD and those who did not
      were compared; the risk factors for FSD were determined. RESULTS: The majority of
      the respondents were younger than 50 years old, predominantly Malays, and had a
      higher academic achievement. The prevalence of FSD in the primary care population
      was 29.6%. The prevalence of women with lack of orgasms, low sexual arousal, lack
      of lubrication, sexual dissatisfaction, and sexual pain were 59.1%, 60.9%, 50.4%,
      52.2%, and 67.8%, respectively. CONCLUSION: The risk factors for FSD are older
      age, Malays, married longer (more than 14 years), having less sexual intercourse
      (less than 1-2 times a week), having more children, married to an older husband
      (aged >42 years), and having a higher academic status. Lack of lubrication is
      found to be the main predictor for FSD in this study. Is lack of lubrication a
      cause or a complication of FSD? Prospective research is needed in the near
      future.

PMID- 17040487
TI  - Lung function, arterial saturation and oxygen uptake in elite cross country
      skiers: influence of exercise mode.
AB  - Arterial desaturation during exercise is common in endurance-trained athletes, a
      phenomenon often more pronounced when the muscle mass engaged in the exercise is
      large. With this background, the present study monitored seven international
      level cross country skiers performing on a treadmill while running (RUN), double
      poling (DP; upper body exercise) and diagonal skiing (DIA; arm and leg exercise).
      Static and dynamic lung function tests were performed and oxygen uptake was
      measured during submaximal and maximal exercise. Lung function variables
      (including the diffusion capacity) were only 5-20% higher than reported in
      sedentary men. Vital capacity was considerably lower than expected from the
      skiers' maximal oxygen uptake (VO(2max)), but the maximal ventilation followed a
      linear relationship with VO(2max). None or only a mild desaturation was observed
      in DP, RUN and DIA. Blood lactate concentration was slightly higher in DIA than
      in DP but not different from RUN. In DIA, VO(2max) was 6.23 +/- 0.47 L/min (mean
      +/- SD), which was 3.8% and 13.9% higher than in RUN and DP, respectively, with
      similar peak heart rates for the three exercise modes. No relationships were
      present either between the degree of desaturation and pulmonary functions tests,
      or with peak oxygen uptakes. The low blood lactate accumulation during the
      exhaustive efforts contributed to the arterial oxygen saturation being mild in
      spite of the very high oxygen uptake observed in these skiers.

PMID- 17040488
TI  - Integration of omics data: how well does it work for bacteria?
AB  - In the current omics era, innovative high-throughput technologies allow measuring
      temporal and conditional changes at various cellular levels. Although individual
      analysis of each of these omics data undoubtedly results into interesting
      findings, it is only by integrating them that gaining a global insight into
      cellular behaviour can be aimed at. A systems approach thus is predicated on data
      integration. However, because of the complexity of biological systems and the
      specificities of the data-generating technologies (noisiness, heterogeneity,
      etc.), integrating omics data in an attempt to reconstruct signalling networks is
      not trivial. Developing its methodologies constitutes a major research challenge.
      Besides for their intrinsic value towards health care, environment and industry,
      prokaryotes are ideal model systems to further develop these methods because of
      their lower regulatory complexity compared with eukaryotes, and the ease with
      which they can be manipulated. Several successful examples outlined in this
      review already show the potential of the systems approach for both fundamental
      and industrial applications, which would be time-consuming or impossible to
      develop solely through traditional reductionist approaches.

PMID- 17040490
TI  - Identification of the core transmembrane complex of the Legionella Dot/Icm type
      IV secretion system.
AB  - Type IV secretion systems (T4SS) are utilized by a wide range of Gram negative
      bacteria to deliver protein and DNA substrates to recipient cells. The best
      characterized T4SS are the type IVA systems, which exhibit extensive similarity
      to the Agrobacterium VirB T4SS. In contrast, type IVB secretion systems share
      almost no sequence homology to the type IVA systems, are composed of
      approximately twice as many proteins, and remain largely uncharacterized. Type
      IVB systems include the Dot/Icm systems found in the pathogens Legionella and
      Coxiella and the conjugative apparatus of IncI plasmids. Here we report the first
      extensive characterization of a type IVB system, the Legionella Dot/Icm secretion
      apparatus. Based on biochemical and genetic analysis, we discerned the existence
      of a critical five-protein subassembly that spans both bacterial membranes and
      comprises the core of the secretion complex. This transmembrane connection is
      mediated by protein dimer pairs consisting of two inner membrane proteins, DotF
      and DotG, which are able to independently associate with DotH/DotC/DotD in the
      outer membrane. The Legionella core subcomplex appears to be functionally
      analogous to the Agrobacterium VirB7-10 subcomplex, suggesting a remarkable
      conservation of the core subassembly in these evolutionarily distant type IV
      secretion machines.

PMID- 17040491
TI  - Different roles of P1 and P2 Saccharomyces cerevisiae ribosomal stalk proteins
      revealed by cross-linking.
AB  - The stalk is an essential domain of the large ribosomal subunit formed by a
      complex of a set of very acidic proteins bound to a core rRNA binding component.
      While in prokaryotes there is only one type acidic protein, L7/12, two protein
      families are found in eukaryotes, phosphoproteins P1 and P2, which presumably
      have different roles. To search for differences zero-length cross-linking by S-S
      bridge formation was applied using Saccharomyces cerevisiae mutant P1 and P2
      proteins carrying single cysteine residues at various positions. The results show
      a more exposed location of the N-terminal domain of the P2 proteins, which in
      contrast to P1, can be found as dimers when the Cys is introduced in this domain.
      Similarly, the Cys containing C-terminal domain of mutant P2 proteins shows a
      notable capacity to form cross-links with other proteins, which is considerably
      lower in the P1 type. On the other hand, mutation at the conserved C-domain of
      protein P0, the eukaryotic stalk rRNA binding component, results in removal of
      about 14 terminal amino acids. Protein P2, but not P1, protects mutant P0 from
      this truncation. These results support a eukaryotic stalk structure in which P1
      proteins are internally located with their C-terminals having a restricted
      reactivity while P2 proteins are more external and accessible to interact with
      other cellular components.

PMID- 17040492
TI  - The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of
      laccase in Cryptococcus neoformans.
AB  - Hsp70 proteins are a well-known class of chaperones that have also been described
      to have roles in cellular regulation. Here, we show that a Cryptococcus
      neoformans Hsp70 homologue Ssa1 acts as a DNA-binding transcriptional co
      activator of the fungal virulence factor, laccase, via binding to a GC-rich
      element within the 5'-UAS in response to glucose starvation, iron, copper,
      calcium and temperature. In addition, Ssa1 forms a regulatory complex with heat
      shock transcription factor and TATA-binding protein during laccase induction.
      Furthermore, deletion of Ssa1 results in reduced laccase and attenuated virulence
      using a mouse model. These results indicate that Hsp70 functions as a stress
      related transcriptional co-activator required for fungal virulence.

PMID- 17040493
TI  - Recent advances in chemical peeling in Japan.
AB  - Chemical peeling is one of the dermatological treatments available for certain
      cutaneous diseases and conditions or aesthetic improvement. This treatment
      consists of the application of one or more chemical agents to the skin. Recently
      in Japan, chemical peeling has been very popular for medical as well as aesthetic
      treatment. Because the scientific background and an adequate approach have not
      been completely established, medical and social problems have been reported. To
      address these issues, the Japanese Dermatological Association has established
      standard guidelines for chemical peeling, and the scientific background and
      validity of chemical peeling has been assessed. In this review, a set of
      guidelines for chemical peeling is introduced, and we will discuss several
      clinical and histological studies including the effects of glycolic acid, and the
      application of deer peeling to skin tumors in our department.

PMID- 17040494
TI  - Vitamin D3 upregulated protein 1 (VDUP1) is a regulator for redox signaling and
      stress-mediated diseases.
AB  - Vitamin D(3) upregulated protein 1 (VDUP1) is a 46-kDa multifunctional protein,
      initially isolated in HL-60 cells as a protein of which expression is upregulated
      by vitamin D(3) administration. Subsequently, it was identified independently by
      investigators from diverse scientific backgrounds as a thioredoxin binding
      protein that negatively regulates the expression and the activity of thioredoxin,
      and is thus involved in redox regulation. Further studies have revealed that
      VDUP1 plays multiple roles in a wide range of cellular processes such as
      proliferation or apoptosis. Recently, it has been reported that VDUP1 is also
      involved in the immune system via positive regulation of natural killer
      development. In addition, VDUP1 has been revealed to be associated with the fatty
      acid utilization. In the present review, we discuss the novel aspects of VDUP1
      function as well as the historical background of VDUP1. Future studies will
      explore the diagnostic and therapeutic potential of modulating the function of
      VDUP1 in vivo.

PMID- 17040495
TI  - Collagen-poly glycolic acid hybrid matrix with basic fibroblast growth factor
      accelerated angiogenesis and granulation tissue formation in diabetic mice.
AB  - Because poor skin wound healing associated with diabetes is thought to be partly
      a result from impaired angiogenesis, treatments that improve angiogenesis could
      have important clinical applications. We herein report the effects of novel
      developed material, collagen-poly glycolic acid fiber hybrid matrix, being used
      together with basic fibroblast growth factor to promote wound healing of full
      thickness skin defects on the back of type 2 diabetic Lepr(db) mice. Our data
      indicates that this therapeutic approach markedly promotes angiogenesis and
      granulation tissue formation in comparison with other conditions 14 days after
      wounding.

PMID- 17040496
TI  - Bidens pilosa suppresses interleukin-1beta-induced cyclooxygenase-2 expression
      through the inhibition of mitogen activated protein kinases phosphorylation in
      normal human dermal fibroblasts.
AB  - Bidens pilosa (BP) Linn. var. radiata is a plant used in traditional folk
      medicine. It is clinically effective in various diseases; the pathogenesis of
      most of these involves cyclooxygenase (COX)-2. To investigate the mechanism on
      which the clinical effectiveness of BP is based, we examined its effects on COX-2
      expression and its major product, prostaglandin (PG)E(2), under conditions of
      inflammation. We induced inflammation in normal human dermal fibroblasts with
      interleukin (IL)-1beta and examined the effects of BP on COX-2 expression and
      PGE(2) production using Western blotting and competitive enzyme immunoassay,
      respectively. The functional involvements of mitogen activated protein kinases
      (MAPK) ERK1/2, p38, and JNK in COX-2 expression were also examined by Western
      blotting. IL-1beta-induced COX-2 expression was regulated by MAPK pathways,
      especially by p38. BP inhibited the phosphorylation of MAPKs, COX-2 expression,
      and subsequent PGE(2) production. The physiological activities and clinical
      effectiveness of BP observed under diverse conditions may be partly attributable
      to its ability to inhibit MAPK, mainly p38, activity, COX-2 expression, and
      subsequent PGE(2) production.

PMID- 17040497
TI  - Application of the Food and Drug Administration (FDA) bioequivalent guidance of
      topical dermatological corticosteroid in yellow-skinned Japanese population:
      validation study using a chromameter.
AB  - The American Food and Drug Administration (FDA) bioequivalent guidance of topical
      dermatological corticosteroids in 1995 (the Guidance) requires measurement of the
      skin blanching response with a chromameter for evaluation of cutaneously applied
      corticosteroid formulations. The Japanese government decided to apply the same
      guidelines in 2003, despite there having been no reported trial for the yellow
      skinned races. The purpose of this study was to obtain basic data of
      corticosteroid-induced skin blanching response measured with a chromameter on
      yellow-skinned races. Four studies were performed according to the Japanese
      version of the Guidance for Industry using a chromameter on the forearms of
      healthy Japanese volunteers. This involved: (i) a validation study of proper
      duration of treatment exposure (dose duration); (ii) a comparison study of two
      dermatological corticosteroid products that represented different potency
      classes; (iii) inspection of reproducibility using right and left forearms; and
      (iv) study of seasonal difference. We showed that: (i) the same medication can
      give different values of ED(50) (the dose duration required to achieve 50% of the
      fitted areas under the effect curves [AUEC](max) value) under different dose
      durations; (ii) ED(50) do not always represent the potency of the corticosteroid;
      (iii) the results of AUEC at maximum duration were similar, but AUEC at an
      approximate ED(50) duration time varied widely; and (iv) the results of AUEC were
      different according to season. In conclusion the dose duration relationships,
      determination of the AUEC(max), and the ED(50) could be obtained on yellow
      skinned races using the FDA method. However, negligible differences were found in
      our study regarding dose duration, reproducibility and seasonal change.

PMID- 17040498
TI  - Novel mutation (Asp158Val) in H1 domain of keratin 5 gene in a Japanese patient
      with Kobner-type epidermolysis bullosa simplex.
AB  - We describe a 19-year-old Japanese male with Kobner-type epidermolysis bullosa
      simplex (EBS-KB) with a novel keratin gene mutation. The patient developed
      blisters on the feet, palms, elbows and knees soon after birth. His father is
      similarly affected with blistering, but his mother and younger brother are not
      affected. Histological examination revealed that the primary separation in the
      blister occurred within the basal cell layer. Sequence analysis demonstrated an A
      to-T transition at the second position of codon 158 in the keratin 5 (K5) gene.
      The amino acid at codon 158 was deduced to have changed from asparagine to
      valine. We identified a novel mutation (Asp158Val) in the H1 domain of the K5
      gene in this Japanese patient with EBS-KB. This is the first gene mutation report
      of EBS-KB in the H1 domain of the K5 gene.

PMID- 17040499
TI  - Androgenetic alopecia in adolescents: a report of 43 cases.
AB  - Androgenetic alopecia (AGA) is the most common type of hair loss in adults, but
      it also occurs in adolescents, though its prevalence among this younger
      population is not well established. The purpose of this study was to evaluate the
      clinical manifestations and endocrine status of adolescent patients with AGA in
      Korea. This 5-year (January 2001-August 2005) clinical study involved 43
      adolescent patients with AGA. Testosterone and dehydroepiandrosterone sulfate
      (DHEA-S) laboratory studies were undertaken to investigate androgenic hormonal
      effects. Hair loss severity was categorized using the Hamilton-Norwood and Ludwig
      classifications. Gender ratio showed a male predominance (M : F, 35:8), and a
      mean age at onset of 16.8 years. These adolescent patients showed milder symptoms
      than adults, and a family history of alopecia was found in 72.1%, which is
      greater than that reported in adults, which ranges 30.9-64.5%. Seborrheic
      dermatitis (27.9%) was the condition most commonly associated with AGA among our
      study subjects, followed in descending order by acne vulgaris and atopic
      dermatitis. Serum levels of testosterone and DHEA-S were within normal limits,
      except in one subject. Our study shows the clinical characteristics of AGA in
      Korean adolescents.

PMID- 17040500
TI  - Reverse sural artery flap for distal lower extremity defects.
AB  - Traumatic and various dermatological conditions resulting in skin and
      subcutaneous tissue loss on the lower limb cause a therapeutic challenge for the
      dermatological surgeon, because this anatomical location lacks adequate skin
      laxity and has limited local soft tissue, especially around the heel. In this
      report, we present our experience with the reverse sural artery flap on seven
      patients. The soft tissue defect was traumatic in two patients. We also treated
      three diabetic patients. There were no immediate or late surgical complications
      in four cases; flap and donor site healing was uneventful. The remaining three
      cases were diabetic, and all presented with the following complications:
      rejection of split skin graft at donor site, infection at the flap border and
      superficial flap necrosis. The flap necrosis was concluded to be at least in part
      due to the patient's noncompliance with postoperative measures. We conclude that
      the reverse sural artery flap is a satisfactory alternative in the reconstruction
      of lower limb defects, but we also feel that the importance of proper evaluation
      prior to surgery in terms of vascular impairment and patient compliance should be
      emphasized to ensure a successful surgical outcome.

PMID- 17040501
TI  - Drug eruption caused by the nonionic contrast medium iohexol. "Recall-like
      phenomenon" appearing on an area previously affected by herpes zoster.
AB  - We report a case of "recall-like phenomenon" caused by nonionic contrast medium.
      A 62-year-old woman suffering from postherpetic neuralgia developed erythematous
      plaques 12 h after an intercostal nerve block under X-ray guidance using iohexol
      (Omnipaque) as contrast medium. The erythematous plaques were preferentially
      located in the sites where she had experienced herpes zoster 4 months previously.
      The lesions cleared spontaneously leaving no pigmentation. Both patch testing and
      intradermal testing with iohexol and ioversol were positive. We postulate that
      local immunological changes in the skin, such as an increased number and/or
      accelerated activity of Langerhans cells and mast cells in the herpes zoster
      lesions, were responsible for this phenomenon. This "recall-like phenomenon",
      occurring preferentially in skin previously affected by herpes zoster, could
      facilitate understanding of the pathology of drug eruptions.

PMID- 17040502
TI  - Generalized morphea and primary biliary cirrhosis coexisting in a male patient.
AB  - We present further evidence that generalized morphea (GM) and primary biliary
      cirrhosis (PBC) may be associated. As far as we know, only six cases with this
      association have been previously reported in the published work, all of which
      were observed in women. We describe the case of a 62-year-old man diagnosed with
      M2-antibody-positive PBC who developed multiple generalized indurated plaques on
      the trunk and extremities 3 years later. Clinical history, laboratory data and
      histopathological examination were consistent with the diagnosis of GM. The
      coexistence in a male of these two entities that predominantly affect females
      reinforces the hypothesis that a pathogenic link exists between GM and PBC.
      Consequently, PBC should be looked for in all patients with GM.

PMID- 17040503
TI  - Juvenile-onset hypergammaglobulinemic purpura and fetal congenital heart block.
AB  - Waldenstrom's hypergammaglobulinemic purpura (HGP) is a rare chronic disorder
      characterized by recurrent purpura on the legs, a polyclonal increase in serum
      gamma-globulin, an elevated erythrocyte sedimentation rate and a positive
      rheumatoid factor. A 30-year-old primigravid woman with 14 years of HGP was found
      to have fetal bradycardia at 25 weeks' gestation. Laboratory investigations
      demonstrated positive anti-Ro/SSA and anti-La/SSB antibodies in the maternal
      serum. Cesarean delivery was performed at 39 weeks, and a 2750-g female infant
      was born with complete atrioventricular block. Fortunately, the neonatal period
      has been uneventful without need for pace-making. Maternal HGP exacerbated just
      after delivery, but resolved within 1 week without treatment. Physicians should
      be aware of the possible presence of neonatal lupus-related anti-Ro/SSA and anti
      La/SSB autoantibodies in patients with HGP. Screening for these autoantibodies is
      important and could be used as a marker to identify and manage high-risk
      pregnancies.

PMID- 17040504
TI  - Granuloma caused by subcutaneous injection of leuprorelin acetate product: case
      report and histopathological findings.
AB  - Leuprorelin acetate is a luteinizing hormone-releasing hormone (LH-RH) analog,
      which is used for chemical castration. Chemical castration treatment has an
      especially important role for prostate cancer. To ensure ongoing chemical
      castration, a novel sustained-action injection system using spherical
      microcapsules has been developed. We report a patient who had granuloma caused by
      administration of the 11.25 mg leuprorelin acetate product. Histological
      examination revealed many giant cells with vacuoles. On the basis of reported
      cases, these vacuoles are characteristic for the granuloma caused by leuprorelin
      acetate product. The vacuoles in the granuloma are the same size as the
      microcapsules, and their shape is almost spherical. We assume that the vacuoles
      in the granuloma are actually the microcapsules. We expect that there will be
      investigations regarding the procatarctic cause of granuloma formation.

PMID- 17040505
TI  - Case of morphea occurring on a scar after laparoscopy.

PMID- 17040506
TI  - Case of co-morbidity of alopecia areata and pityriasis lichenoides in a five year
      old boy for two years.

PMID- 17040507
TI  - Cicatricial pemphigoid with widespread bullous eruption.

PMID- 17040508
TI  - Measuring and reporting what matters: a cornerstone for evidence-based health
      care.

PMID- 17040509
TI  - Evidence-based nursing practice: making progress and making a difference.

PMID- 17040510
TI  - State-of-the-evidence reviews: advantages and challenges of including grey
      literature.
AB  - BACKGROUND: Increasingly, health policy decision-makers and professionals are
      turning to research-based evidence to support decisions about policy and
      practice. Systematic reviews are useful for gathering, summarizing, and
      synthesizing published and unpublished research about clearly defined
      interventions. State-of-the-evidence reviews are broader than traditional
      systematic reviews and may include not only published and unpublished research,
      but also published and unpublished non-research literature. Decisions about
      whether to include this "grey literature" in a review are challenging and lead to
      many questions about whether the advantages outweigh the challenges. AIMS: The
      primary purpose of this article is to describe what constitutes grey literature,
      and methods to locate it and assess its quality. The secondary purpose is to
      discuss the core issues to consider when making decisions to include grey
      literature in a state-of-the-evidence review. METHODS: A recent state-of-the
      evidence review is used as an exemplar to present advantages and challenges
      related to including grey literature in a review. RESULTS: Despite the
      challenges, in the exemplar, inclusion of grey literature was useful to validate
      the results of a research-based literature search. CONCLUSION: Decisions about
      whether to include grey literature in a state-of-the-evidence review are complex.
      A checklist to assist in decision-making was created as a tool to assist the
      researcher in determining whether it is advantageous to include grey literature
      in a review.

PMID- 17040511
TI  - Constructing a new approach to developing evidence-based practice with nurses and
      older people.
AB  - PURPOSE: Providing evidence-based nursing care to older people is central to the
      international development agenda. This paper is a report on the first 5 years
      (2000-2005) of a participatory research project, the purpose of which was to
      collaborate with practitioners and older people to develop approaches to promote
      the attainment of evidence-based nursing care across Scotland. DESIGN: Many
      theoretical influences shaped the design of this action research study including
      realistic evaluation, participatory social learning theory, and descriptions of
      communities of practice. Multiple methods of data collection were used during
      four action cycles. The inaugural community of practice comprised 30 nurses, a
      second group of 30 nurses joined midway, followed by a third group of 15 nurses,
      and finally, an older person-carer community of 21 members was established.
      FINDINGS: Project outputs included the construction of an internet-based,
      practice-development college. A procedural model for developing and demonstrating
      care guidance drawn from a diversity of evidence and reflective of an agreed set
      of principles was piloted and endorsed by the national standard setting agency. A
      preliminary version of a promising approach to practice development, "the
      Caledonian Model," was delineated for future testing and refinement. CONCLUSION:
      This work indicates the merits of using participatory research to find solutions
      to the challenge of promoting evidence-based practice. Evaluation data suggest
      that in combination, the approaches developed in this project empower nurses to
      work with older people to champion developments even in seemingly unfavorable
      conditions.

PMID- 17040512
TI  - Development and testing of tools to assess physical restraint use.
AB  - BACKGROUND: To implement best practice in restraint use, healthcare providers and
      decision makers require current, accurate, and easily accessible information
      about restraint practices in their setting. There is a need for a reliable and
      valid instrument that is feasible for use in these settings to rapidly assess
      physical restraint use. METHOD: Two instruments to assess physical restraint use
      were developed and tested: an observation tool and a chart audit. The instruments
      were tested in complex continuing care units and rehabilitation units at two
      healthcare organizations. The restraint use observation tool was administered by
      trained observers in a series of five observations over a 2-week period. Chart
      audits were conducted for a sample of residents. Inter-rater agreement of the
      observation tool and chart audit was assessed. Point prevalence estimates were
      obtained for each site. The time required to use the observation tool and
      complete chart audits as well as the comparability of findings from the two data
      sources were described. FINDINGS: Restraint use observations were completed for
      289 patients and chart audits were completed for 207 patients. Prevalence and
      patterns of restraint use varied between sites and across time periods.
      Observations took an average of 2.6 (Site A) and 0.6 (Site B) minutes per
      patient. There was excellent inter-rater agreement for most items on the
      observation tool with the exception of whether or not the patient was able to
      release or loosen the restraint. There was significant concordance but as
      expected, not complete agreement between paired estimates of prevalence using the
      observational tool and the chart audit. CONCLUSION: The observation and chart
      audit tools are feasible to use and reliably assess physical restraint use in
      healthcare organizations. The patient's physical capacity to move independently,
      the patient's waking status, and the restraint's restriction of mobility are
      items that should be added to the observation tool. The tools are complementary
      and should be used in tandem to capture the multifaceted complexity of restraint
      use in health service organizations.

PMID- 17040514
TI  - Re: Letter submission "Antiseptic obstetric cream for pelvic examination: where
      is the evidence?".

PMID- 17040517
TI  - Moral geographies of restraint in nursing homes.

PMID- 17040518
TI  - A systematic review of the safety and effectiveness of restraint and seclusion as
      interventions for the short-term management of violence in adult psychiatric
      inpatient settings and emergency departments.
AB  - AIMS: The aim of this review was to assess whether restraint and seclusion are
      safe and effective interventions for the short-term management of
      disturbed/violent behaviour. Staff and service user perspectives on the use of
      these interventions were also considered. The review was undertaken as part of
      the development process for a national guideline on the short-term management of
      disturbed/violent behaviour in adult psychiatric inpatient settings and emergency
      departments in the United Kingdom. METHOD: An exhaustive literature search was
      undertaken. Systematic reviews, before and after studies, as well as qualitative
      studies were included. Searches were run from 1985 to 2002. FINDINGS: Thirty-six
      eligible studies were identified. However, none were randomised controlled
      trials. Most of the included studies had many limitations, such as small sample
      sizes, confounders not adequately accounted for, potential selection bias, poorly
      reported results, and lack of clarity as to whether mechanical restraints were
      used. This review must therefore be viewed as a mapping exercise, which
      illustrates the range and quality of studies that have been undertaken in this
      area to date. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Insufficient evidence is
      available to determine whether seclusion and restraint are safe and/or effective
      interventions for the short-term management of disturbed/violent behaviour in
      adult psychiatric inpatient settings. These interventions should therefore be
      used with caution and only as a last resort once other methods of calming a
      situation and/or service user have failed.

PMID- 17040519
TI  - Evidence base for practice: reduction of restraint and seclusion use during child
      and adolescent psychiatric inpatient treatment.
AB  - BACKGROUND: Restraint and seclusion of children has great potential for harm.
      Since the mid-1980s, psychiatric inpatient personnel for children and adolescents
      have put considerable energy in reducing the use of extreme measures of
      aggression management. While the use of restraints is a particular problem in the
      United States, aggression management and means of control in psychiatric settings
      is an international issue. APPROACH: The core question of this review was: What
      is the current state of the evidence supporting restraint reduction efforts with
      children and adolescents? Studies were reviewed and critiqued that related to
      programs of restraint reduction, restraint reduction methods, and aggression
      management. Internationally, there seems to be more emphasis on reducing coercive
      measures by understanding the context of their use. Thus, studies exploring staff
      perceptions and decisions concerning coercive measures were also examined.
      FINDINGS: The evidence supporting restraint reduction methods in the United
      States comes mainly from case study reports of clinical sites' quality
      improvement projects. Consequently, a collection of studies is accumulating that
      supports a multi-strategy approach to restraint reduction. Limited evidence
      exists for aggression management measures and training in de-escalation
      techniques. Controversial aggression management techniques such as the use of pro
      re nata medication and holding continue to be used with very little support for
      their efficacy. RECOMMENDATIONS: Recommendations include taking a view of
      restraint and seclusion as emergency measures to address dangerous aggression,
      not interventions examined in controlled studies. As such it is suggested that
      sites pool data on restraint use and reduction efforts to create a database for
      benchmarking and studying variations among hospitals. Furthermore, attention
      should also be given to developing additional means for addressing aggressive
      behaviors.

PMID- 17040520
TI  - Patient choice: an influencing factor on policy-related research to decrease
      bedrail use as physical restraint.
AB  - BACKGROUND: This paper shows patients' enactment of choice in mixed methods,
      multidisciplinary study on the use of bedrails as restraints. APPROACH: Under the
      pressure of the implementation of impending legislation, patients from a Canadian
      elderly care rehabilitation unit were recruited to be part of this study and
      assigned to either a study or control group. Study group patients were exposed to
      a new facility policy on restraints in which bedrails were not to be used on a
      patient's bed except under specified conditions. Patients in the control group
      continued to have bedrails on a routine basis according to the facility's old
      policy. Following group assignments, patients could choose to crossover to either
      the control or study group based on their opinions about bedrails. FINDINGS:
      After patients crossed over into either the study or control group, findings for
      the new groups differed significantly. Participants in the rails-up group had
      lower admission Functional Independence Measure scores (p = .001) and higher
      admission Cumulative Illness Rating scores (p = .000) compared to those in the
      rails-down group. CONCLUSIONS: Patients have specific concerns related to the use
      of bedrails that might affect implementing bedrail minimization policies.
      Additionally, the authors conclude that patients' input into research design may
      increase patients' support of the protocol and help maintain study integrity.

PMID- 17040522
TI  - Teaching EBP: the critical step of critically appraising the literature.

PMID- 17040523
TI  - Resources for evidence-based practice.

PMID- 17040524
TI  - The politics of evidence-based practice.

PMID- 17040525
TI  - Contextual factors influencing research use in nursing.
AB  - BACKGROUND: Contextual factors are perceived to be significant barriers to
      research-utilisation-related activity, but little is known about how context
      impacts on specific research-based decisions, or how the individual interacts
      with the organisation in the requirement for research-based change. AIM: This
      study describes the impact of contextual factors on the practical reasoning of
      nurse specialists in the construction of policy for practice. METHODS: Three
      groups of clinical nurse specialists were observed during a series of meetings
      convened to construct evidence-based guidelines for nursing practice. Transcripts
      of the meetings were analysed to identify and categorise the physical, social,
      political, and economic influences on 31 nursing issues. FINDINGS: Multiple
      contextual factors influenced each decision made, with decisions about nursing
      practice bounded by setting and system considerations, relationships with others
      in the care team, and resource constraints. Practitioners were involved in
      weighing up alternative scenarios, contexts, and contingencies for each decision,
      requiring strategies to adapt and reconstruct the nature of care, to influence
      others, and to affect organisational decision-making processes. DISCUSSION: The
      practical accomplishment of evidence-based practice required diverse skills:
      translating between evidence and practice; mediating the values, preferences, and
      working practices of multiple stakeholders; negotiating organisational complexity
      and the management of boundaries; and coordinating inter-organisational and inter
      agency working. Nurse specialists in this study had a significant role in
      instigating, fuelling, and coordinating policy review, predominantly by
      communication across professional and organisational boundaries.
      IMPLICATIONS/CONCLUSIONS: Clinical specialists acting as organisational boundary
      spanners require skills in the informal cultural work of organising,
      facilitating, and maintaining links across professional, team, and organisational
      boundaries. If their role in the negotiation of evidence-based practice patterns
      across professional and organisational boundaries is to be successful, wider
      skills than information management need to be recognised and their development
      and enactment supported.

PMID- 17040526
TI  - Barriers and facilitators influencing call center nurses' decision support for
      callers facing values-sensitive decisions: a mixed methods study.
AB  - BACKGROUND: Call center nurses triage symptoms and provide health information.
      However, information alone is not adequate for people facing values-sensitive
      health decisions. For these decisions, effective interventions are evidence-based
      patient decision aids and in-person nurse coaching using a structured process.
      Little is known about the quality of decision support provided by call center
      nurses. AIMS: To identify the barriers and facilitators influencing the provision
      of decision support by call center nurses to callers facing values-sensitive
      health decisions at a Canadian province-wide health call center. METHODS: A mixed
      qualitative and quantitative descriptive study from December 2003 to January 2004
      using key informant interviews (n= 4), two focus groups (n= 7), a barriers
      assessment survey (n= 57), and analysis of simulated patient calls (n= 38) were
      carried out. Triangulation of these data was conducted using a conceptual content
      analysis method. RESULTS: Participants indicated positive attitudes toward call
      center nurses preparing callers facing values-sensitive decisions. Facilitators
      included decision support resources, nurses' ability to recognize callers having
      difficulty, and having a supportive organizational infrastructure. The most
      frequently identified barriers were (a) limited usability of patient decision
      aids via telephone; (b) lack of a structured process to guide nurses during these
      types of calls; (c) nurses' inadequate knowledge, skills, and confidence in
      providing values-sensitive decision support; (d) unclear program direction; (e)
      organizational pressure to minimize call length; and (f) low public awareness of
      the services. CONCLUSIONS AND IMPLICATIONS: Despite call center nurses having
      positive attitudes, several modifiable barriers were interfering with nurses'
      current approaches to supporting callers facing values-sensitive decisions.
      Nurses wanted educational opportunities to further develop their decision support
      knowledge and skills, and decision support resources that are easier to use via
      telephone. As well, changes to organizational policies that address identified
      barriers could further facilitate the provision of decision support.

PMID- 17040527
TI  - Evaluating psychiatric nurses' awareness of evidence-based nursing publications.
AB  - BACKGROUND: Research has shown that nurses lack skills to find and appraise
      research literature, lack time and organisational support to utilise research,
      and need user-friendly research material to implement evidence-based health care
      in practice. In Sweden, the concept of evidence-based health care has been
      introduced by The Swedish Council on Technology Assessment in Health Care (SBU),
      a concept which the nursing profession quickly adopted. This study was initiated
      synchronously with the publication of two reports on evidence-based nursing (EBN)
      in psychiatric care. AIM: To investigate the dissemination and awareness of
      literature on EBN among psychiatric nurses in Sweden, and more specifically
      whether nurses were aware of the EBN reports. METHODS: A postal questionnaire was
      used with a prospective pre-post design. A questionnaire was constructed and
      distributed to the members in The National Association of Psychiatric Nurses at
      two occasions--before publication of the two reports and 1 year post-publication.
      The questionnaire was initially circulated to 2,294 nurses. The response rate for
      the first distribution was 82% and for the second 72%. RESULTS: Although the
      results demonstrate an increase in awareness concerning the concept of EBN and
      access to literature between data collection, there were still many nurses who
      reported no access to the literature. The reported use of literature in practice
      was scarce; however, findings demonstrated an increase in opinion about the value
      of using literature in practice. CONCLUSIONS: The findings of this study
      demonstrate that the dissemination of literature in EBN, as well as EBN
      literature in psychiatric care, still requires considerable development to assure
      its use in practice. IMPLICATIONS: The diffusion and dissemination of evidence
      based literature within nursing must be guided by a structured plan followed by
      concrete examples of its implication(s) for practice.

PMID- 17040528
TI  - Teaching EBP: getting to the gold: how to search for the best evidence.

PMID- 17040530
TI  - Resources for evidence-based practice.

PMID- 17040531
TI  - Implementing the evidence--how warm is the climate?

PMID- 17040532
TI  - Outcomes and implementation strategies from the first U.S. Evidence-Based
      Practice Leadership Summit.

PMID- 17040533
TI  - Performing subcutaneous injections: a literature review.
AB  - BACKGROUND: Persons using daily subcutaneous injections to administer medicine
      perform them in different ways and thereby increase the risk of skin
      complications related to the injection. It is often part of nurses' role to
      administer medicine and educate the patient in injection technique. Course
      literature in nursing education, commercial patient education pamphlets, and
      instructional leaflets do not give consistent advice regarding subcutaneous
      injection technique. AIM: The aim of this review was to identify the scientific
      foundation for the technical performance of subcutaneous injections. The question
      to be answered was: How should a subcutaneous injection be administered to
      achieve the right dose in the right place with minimum complications? METHOD: The
      review included a search in three databases, a screening process at abstract
      level, followed by a quality assessment of included articles. The quality
      assessment was done independently by two people and followed specific protocols.
      RESULT: A total of 38 articles were assessed for quality and covered information
      on dose, location, and complications of subcutaneous injection. The assessed
      studies are heterogeneous in design and describe different aspects of the
      subcutaneous injection technique. Therefore, the scientific foundation for
      technical performance is weak. However, several studies indicate that the amount
      of subcutaneous fat and appropriate needle length are of high importance for the
      drug to reach the target tissue. CONCLUSION: More research regarding effective
      subcutaneous injection technique needs to be done.

PMID- 17040534
TI  - Developing postoperative pain management: utilising the promoting action on
      research implementation in health services (PARIHS) framework.
AB  - BACKGROUND: The development of acute pain services (APS), education programmes,
      and protocols assumed an expectation that health care professionals would
      integrate evidence into everyday practice. However, research evidence into pain
      management would suggest that this is not the case. APPROACH: Through a review of
      the literature, the authors aim to (1) explore the factors that have a
      significant influence on getting evidence into practice (using the PARIHS model
      as a guide) and (2) examine the relevance of these factors to postoperative pain
      practices. FINDINGS: The need to assist clinicians with developing a greater
      awareness of the competing and complex influences that surround pain management
      practices is outlined. RECOMMENDATIONS: There is a necessity to adopt a
      systematic, rigorous, and multidimensional approach to pain management issues,
      utilising the PARIHS framework as a guide, to improve pain practices.

PMID- 17040535
TI  - Space, place, and the evidence base: Part II--Rereading nursing environment
      through geographical research.
AB  - This, the second and final article in the short health geography series,
      articulates how, moving beyond the models and assumptions associated with the
      metaparadigm of Nursing Environment, as a focused subdisciplinary approach,
      health geography might provide unique insights into nursing. A case study of a
      fictional yet somewhat typical children's hospital is presented and demonstrates
      some wide-ranging geographical issues and research questions (and hence potential
      geographical data) pertaining to nursing and the allied health professions.
      Indeed, this broad-brush approach is purposeful to make as many connections as
      possible to readers with varied theoretical, methodological, empirical, and
      practice expertise. In addition to the case study, to indicate further how
      geographical inquiry might locate quite comfortably in nursing research, the
      article also makes some initial and tentative connections between geography and
      an established nursing framework for the uptake of research evidence for
      practice. Although it is acknowledged that geographical inquiry should certainly
      never have the first call on researching the relationships between nurses and
      their environments, it is argued that its conceptual focus on space and place
      provides dedicated and detailed attention and a sound basis for a reformed,
      "spatialized" route to a more comprehensive understanding. Moreover, it is argued
      that it also demonstrates great versatility in terms of the scales and the
      subject matter with which it might engage. Some important issues certainly remain
      with respect to what might be the correct form of engagement between geographical
      and nursing research, but arguably, as a reformed disciplinary approach, health
      geography has the potential to provide a wealth of focused evidence for nursing
      practice.

PMID- 17040536
TI  - Teaching EBP: asking searchable, answerable clinical questions.

PMID- 17040538
TI  - Resources for evidence-based practice.

PMID- 17040540
TI  - To synthesise or not synthesise? That is the question!

PMID- 17040541
TI  - Quality improvement and evidence-based practice: As one or at odds in the effort
      to promote better health care?

PMID- 17040542
TI  - Space, place, and the evidence base: Part I--An introduction to health geography.

PMID- 17040543
TI  - Evidence for smoking cessation: Implications for gender-specific strategies.
AB  - BACKGROUND: Facilitating smoking cessation requires an evidence-based approach.
      The Lienhard School of Nursing Institute for Healthy Aging in the United States,
      whose focus is providing health information to aging baby boomers, developed an
      interest in studying strategies for smoking cessation in women. APPROACH: Studies
      were reviewed and critiqued related to the question: What is the relative
      efficacy of first-line smoking cessation interventions for women versus men in
      the 40- to 65-year-old age group? This article first discusses the procedure used
      to construct an integrative framework for finding the evidence on smoking
      cessation, including a literature search and refinement of the problem to be
      studied, and then a summary of the evidence gathered on the selected variable
      (gender) and interventions (counseling, pharmacotherapy, nicotine replacement
      therapy). FINDINGS: Evidence was found that supports the general efficacy of
      three first-line smoking cessation interventions: counseling, bupropion-sustained
      release (BSR), and nicotine replacement therapy (NRT). What the evidence does not
      show, however, is which of these interventions may be more effective for women
      versus men in general or specifically in the 40- to 65-year-old age group.
      RECOMMENDATIONS: Recommendations include the development of a clinical trial and
      the inclusion from the outset of gender as a major variable in all future
      intervention studies. IMPLICATIONS: Practice implications include the fact that
      since effective treatments already exist for assisting clients to stop smoking,
      all health-care providers should offer an intervention that has been found
      effective to any client who expresses a desire to quit smoking. Further studies
      of efficacy are needed to develop more focused implications.

PMID- 17040544
TI  - Research and theory for Nursing and Midwifery: Rethinking the Nature of Evidence.
AB  - BACKGROUND AND RATIONALE: The rise in the principles of evidence-based medicine
      in the 1990s heralded a re-emerging orthodoxy in research methodologies. The view
      of the randomised controlled trial (RCT) as a "gold standard" for evaluation of
      medical interventions has extended recently to evaluation of organisational forms
      and reforms and of change in complex systems-within health care and in other
      human services. Relatively little attention has been given to the epistemological
      assumptions underlying such a hierarchy of research evidence. AIMS AND METHODS:
      Case studies from research in maternity care are used in this article to describe
      problems and limitations encountered in using RCTs to evaluate some recent policy
      driven and consumer-oriented developments. These are discussed in relation to
      theory of knowledge and the epistemological assumptions, or paradigms,
      underpinning health services research. The aim in this discussion is not to
      advocate, or to reject, particular approaches to research but to advocate a more
      open and critical engagement with questions about the nature of evidence.
      FINDINGS AND DISCUSSION: Experimental approaches are of considerable value in
      investigating deterministic and probabilistic cause and effect relationships, and
      in testing often well-established but unevaluated technologies. However, little
      attention has been paid to contextual and cultural factors in the effects of
      interventions, in the culturally constructed nature of research questions
      themselves, or of the data on which much research is based. More complex, and
      less linear, approaches to methodology are needed to address these issues. A
      simple hierarchical approach does not represent the complexity of evidence well
      and should move toward a more cyclical view of knowledge development.

PMID- 17040545
TI  - From workshop to work practice: An exploration of context and facilitation in the
      development of evidence-based practice.
AB  - BACKGROUND: This article examines the process of translating evidence into
      practice using a facilitation model developed by the Western Australian Centre
      for Evidence Based Nursing and Midwifery. AIMS: Using the conceptual framework
      Promoting Action on Research Implementation in Health Services (PARIHS), the aims
      of the study were (1) to explore the relative and combined importance of context
      and facilitation in the successful implementation of a new evidence-based
      clinical practice protocol and (2) to examine the establishment of more lasting
      change to individuals and organizations that resulted in greater incorporation of
      the principles of evidence-based practice (EBP). METHODS: A pre-workshop, semi
      structured telephone survey with 16 nurse managers in six rural hospitals; a
      summative evaluation immediately post-workshop with 54 participants; and follow
      up, semi-structured interviews with 23 workshop participants. FINDINGS: The
      contexts in each of the participating hospitals were very different; of the six
      hospitals, only one had not implemented the new protocol. Five had reviewed their
      practices and brought them in line with the protocol developed at the workshop.
      The rate of adoption varied considerably from 2 weeks to months. The participants
      reported being better informed about EBP in general and were positive about their
      ability to improve their practice and search more efficiently for best practice
      information. Underlying motivations for protocol development should be included
      in the PARIHS framework. IMPLICATIONS FOR EDUCATION: Good facilitation appears to
      be more influential than context in overcoming the barriers to the uptake of EBP.

PMID- 17040546
TI  - Translating fall prevention best practices in the hospital setting: Reflecting on
      McInnes and Askie's (2004) evidence review.

PMID- 17040547
TI  - Teaching EBP: "Getting from zero to one." Moving from recognizing and admitting
      uncertainties to asking searchable, answerable questions.

PMID- 17040549
TI  - Getting evidence into practice: a contact sport.

PMID- 17040550
TI  - A systematic review for effective management of central venous catheters and
      catheter sites in acute care paediatric patients.
AB  - BACKGROUND: Central venous catheters (CVCs) have provided many benefits in modern
      day medical practice; however, they also put patients at risk of catheter-related
      complications. Numerous studies have been carried out in relation to the
      management of central venous catheters with conflicting results. While there were
      several systematic reviews of central venous catheter-related issues, it is clear
      that there was no systematic review of CVC-related studies specific to the
      paediatric population in the acute care setting. OBJECTIVE: To present the best
      available evidence for effective management of central venous catheters and
      catheter sites in the prevention and/or reduction of catheter-related
      complications in hospitalised paediatric patients. METHODS: A systematic review
      was undertaken according to the approach of the Centre for Reviews and
      Dissemination (CRD; http://www.york.ac.uk/inst/crd). DATA SOURCE: Literature was
      identified by electronic searching of Cochrane Library, MEDLINE, CINAHL,
      HealthSTAR, and CancerLit; checking references of all review articles; hand
      searching of key relevant journals and conference proceedings; and contact with
      expert informants, medical suppliers, and pharmaceutical companies.
      INCLUSION/EXCLUSION CRITERIA: The review included randomised and non-randomised
      controlled trials conducted with hospitalised paediatric patients. Studies that
      included mixed adult and paediatric populations and mixed hospitalised and home
      care settings were excluded. DATA EXTRACTION: Two independent reviewers extracted
      data onto a standard data extraction form, with differences resolved by
      discussion. QUALITY ASSESSMENT: The quality assessment of retrieved studies
      included: study design, the degree to which systematic bias was avoided or
      minimised, the degree to which the assessment was "blind," the degree to which
      follow up was completed. DATA SYNTHESIS: Quantitative pooling of studies was not
      feasible due to the diversity of interventions and outcome measures between
      similar studies. A narrative account of the study characteristics and results was
      therefore undertaken. RESULTS: Thirty-eight randomised and quasi-randomised
      controlled trials were retrieved for critical appraisal. Of these, 32 were
      excluded from the review because the studies did not meet the inclusion criteria
      and some lacked reporting of appropriate data. Six studies met the criteria with
      interventions such as antibiotic flushes, antiseptic skin preparations, and
      dressing materials. CONCLUSION: Quality of reporting was generally lacking.
      Statistical pooling of results was not possible due to diversity in the reporting
      of outcomes. There was no evidence to make recommendations on the degree of
      barrier precautions and the type of aseptic technique to be used at the time of
      catheter insertion in the paediatric population to prevent catheter-related
      infection. There was insufficient evidence to support the routine use of an
      antibiotic flushing solution. There was a lack of randomised controlled trial
      (RCT) evidence on the benefit of heparin flushes, the use of in-line filters, the
      frequency of fluid administration set changes, or the type of dressing to use and
      the frequency of dressing changes. There was some evidence to suggest that
      chlorhexidine lotion is superior to povidone iodine as a cutaneous antiseptic at
      the catheter insertion site. However, no recommendation can be made for the use
      of chlorhexidine in neonates less than 2 weeks old or in premature infants. This
      systematic review concluded that there is an urgent need for well-designed
      randomised controlled trials with sufficient power to determine the effectiveness
      of various interventions in relation to management of CVCs.

PMID- 17040552
TI  - The concept of decisional control: building the base for evidence-based nursing
      practice.
AB  - PURPOSES: The purposes of this article are to add clarification to the meaning of
      decisional control and provide a review of research related to the concept.
      DEFINITIONS AND CHARACTERISTICS OF DECISIONAL CONTROL: A summary of the
      definitions of decisional control is followed by a discussion of the
      characteristics of the concept. The concept of decisional control includes the
      ability or power to decide what will be one's involvement in health care
      decisions. REVIEW OF RESEARCH: Studies on decisional control have tended to
      center on inpatient, physician office, or clinic settings with a focus on the
      diagnosis of cancer in which multiple medical treatment decisions arise. Most of
      the research thus far has been performed in the United States and Canada related
      to medical treatment. At this point, it is not entirely clear how patient
      preferences for decisional control relate to health outcomes. MEASURING
      DECISIONAL CONTROL: An overview of the tools available to measure decisional
      control follows the review of the research. FUTURE DIRECTION: Future research
      needs to focus on the identification of the differences in decisional control by
      country, in differing cultural and ethnic groups within countries, and in various
      geographical areas of countries. The relationship of patient characteristics
      (e.g., age, gender, education, and income) to decisional control preferences is
      not clearly identified. A large gap in the research relates to how nurses can
      facilitate preferred decisional control to improve patient outcomes through
      evidence-based nursing practice.

PMID- 17040553
TI  - Sharing empirical knowledge to improve breastfeeding promotion and support:
      description of a research dissemination project.
AB  - BACKGROUND: Effective transfer of research findings to health care settings is a
      shared priority among researchers, clinicians, and decision makers. A
      multidisciplinary, multi-method investigation conducted in 2001 that explored
      breastfeeding practices and support within a large immigrant community in
      Montreal, Quebec, Canada, bore numerous implications for practice. Peer-reviewed
      funding was subsequently granted to support dissemination of these findings to
      relevant stakeholders. METHOD: Key steps in implementing this research
      dissemination project included (1) identifying and attracting target audiences
      from hospitals, community health settings, and government agencies; (2) tailoring
      tools for communication of research findings to the various needs of audiences;
      (3) designing interactive workshops to facilitate knowledge uptake; and (4)
      integrating the project outcomes within a government-sponsored regional
      breastfeeding committee for longer-term impact. FINDINGS: Despite organizational
      challenges, more than 90 health care providers, decision makers, and
      breastfeeding support volunteers participated in the project workshops. Through
      feedback loops, the dissemination activities contributed new layers of
      understanding to the original research findings. The activities also engaged
      audience members to identify more effective breastfeeding support interventions
      and led to the adoption of breastfeeding support priorities shared by hospital,
      community, and government stakeholders. CONCLUSION: This dissemination project
      provided unique opportunities for researchers and stakeholders to share in the
      interpretation of research findings and to strategically plan for future
      interventions to promote and support breastfeeding within ethnically diverse
      communities. Further research dissemination work should continue to be
      theoretically grounded, include systematic, long-term assessment of dissemination
      outcomes, and be adequately financed throughout.

PMID- 17040554
TI  - Clinical practice guideline for the assessment and prevention of falls in older
      people.

PMID- 17040555
TI  - Teaching EBP: a challenge for educators in the 21st century.

PMID- 17040558
TI  - The DAMASK trial protocol: a pragmatic randomised trial to evaluate whether GPs
      should have direct access to MRI for patients with suspected internal derangement
      of the knee.
AB  - BACKGROUND: Though new technologies like Magnetic Resonance Imaging (MRI) may be
      accurate, they often diffuse into practice before thorough assessment of their
      value in diagnosis and management, and of their effects on patient outcome and
      costs. MRI of the knee is a common investigation despite concern that it is not
      always appropriate. There is wide variation in general practitioners (GPs) access
      to, and use of MRI, and in the associated costs. The objective of this study was
      to resolve uncertainty whether GPs should refer patients with suspected internal
      derangement of the knee for MRI or to an orthopaedic specialist in secondary
      care. METHODS/DESIGN: The design consisted of a pragmatic multi-centre randomised
      trial with two parallel groups and concomitant economic evaluation. Patients
      presenting in general practice with suspected internal derangement of the knee
      and for whom their GP was considering referral to an orthopaedic specialist in
      secondary care were eligible for inclusion. Within practices, GPs or practice
      nurses randomised eligible and consenting participants to the local radiology
      department for an MRI examination, or for consultation with an orthopaedic
      specialist. To ensure that the waiting time from GP consultation to orthopaedic
      appointment was similar for both trial arms, GPs made a provisional referral to
      orthopaedics when requesting the MRI examination. Thus we evaluated the more
      appropriate sequence of events independent of variations in waiting times. Follow
      up of participants was by postal questionnaires at six, twelve and 24 months
      after randomisation. This was to ensure that the evaluation covered all events up
      to and including arthroscopy. DISCUSSION: The DAMASK trial should make a major
      contribution to the development of evidence-based partnerships between primary
      and secondary care professionals and inform the debate when MRI should enter the
      diagnostic pathway.

PMID- 17040559
TI  - Pseudo current density maps of electrophysiological heart, nerve or brain
      function and their physical basis.
AB  - BACKGROUND: In recent years the visualization of biomagnetic measurement data by
      so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became
      popular. METHODS: The physical basis of these intuitive maps is clarified by
      means of analytically solvable problems. RESULTS: Examples in
      magnetocardiography, magnetoencephalography and magnetoneurography demonstrate
      the usefulness of this method. CONCLUSION: Hardware realizations of the HC
      transformation and some similar transformations are discussed which could
      advantageously support cross-platform comparability of biomagnetic measurements.

PMID- 17040560
TI  - Independent centromere formation in a capricious, gene-free domain of chromosome
      13q21 in Old World monkeys and pigs.
AB  - BACKGROUND: Evolutionary centromere repositioning and human analphoid
      neocentromeres occurring in clinical cases are, very likely, two stages of the
      same phenomenon whose properties still remain substantially obscure. Chromosome
      13 is the chromosome with the highest number of neocentromeres. We reconstructed
      the mammalian evolutionary history of this chromosome and characterized two human
      neocentromeres at 13q21, in search of information that could improve our
      understanding of the relationship between evolutionarily new centromeres,
      inactivated centromeres, and clinical neocentromeres. RESULTS: Chromosome 13
      evolution was studied, using FISH experiments, across several diverse
      superordinal phylogenetic clades spanning >100 million years of evolution. The
      analysis revealed exceptional conservation among primates (hominoids, Old World
      monkeys, and New World monkeys), Carnivora (cat), Perissodactyla (horse), and
      Cetartiodactyla (pig). In contrast, the centromeres in both Old World monkeys and
      pig have apparently repositioned independently to a central location (13q21). We
      compared these results to the positions of two human 13q21 neocentromeres using
      chromatin immunoprecipitation and genomic microarrays. CONCLUSION: We show that a
      gene-desert region at 13q21 of approximately 3.9 Mb in size possesses an inherent
      potential to form evolutionarily new centromeres over, at least, approximately 95
      million years of mammalian evolution. The striking absence of genes may represent
      an important property, making the region tolerant to the extensive
      pericentromeric reshuffling during subsequent evolution. Comparison of the
      pericentromeric organization of chromosome 13 in four Old World monkey species
      revealed many differences in sequence organization. The region contains clusters
      of duplicons showing peculiar features.

PMID- 17040561
TI  - Prediction of trans-antisense transcripts in Arabidopsis thaliana.
AB  - BACKGROUND: Natural antisense transcripts (NATs) are coding or non-coding RNAs
      with sequence complementarity to other transcripts (sense transcripts). These
      RNAs could potentially regulate the expression of their sense partner(s) at
      either the transcriptional or post-transcriptional level. Experimental and
      computational methods have demonstrated the widespread occurrence of NATs in
      eukaryotes. However, most previous studies only focused on cis-NATs with little
      attention being paid to NATs that originate in trans. RESULTS: We have performed
      a genome-wide screen of trans-NATs in Arabidopsis thaliana and identified 1,320
      putative trans-NAT pairs. An RNA annealing program predicted that most trans-NATs
      could form extended double-stranded RNA duplexes with their sense partners. Among
      trans-NATs with available expression data, more than 85% were found in the same
      tissue as their sense partners; of these, 67% were found in the same cell as
      their sense partners at comparable expression levels. For about 60% of
      Arabidopsis trans-NATs, orthologs of at least one transcript of the pair also had
      trans-NAT partners in either Populus trichocarpa or Oryza sativa. The observation
      that 430 transcripts had both putative cis- and trans-NATs implicates multiple
      regulations by antisense transcripts. The potential roles of trans-NATs in
      inducing post-transcriptional gene silencing and in regulating alternative
      splicing were also examined. CONCLUSION: The Arabidopsis transcriptome contains a
      fairly large number of trans-NATs, whose possible functions include silencing of
      the corresponding sense transcripts or altering their splicing patterns. The
      interlaced relationships observed in some cis- and trans-NAT pairs suggest that
      antisense transcripts could be involved in complex regulatory networks in
      eukaryotes.

PMID- 17040562
TI  - Deep mtDNA divergences indicate cryptic species in a fig-pollinating wasp.
AB  - BACKGROUND: Figs and fig-pollinating wasps are obligate mutualists that have
      coevolved for ca. 90 million years. They have radiated together, but do not show
      strict cospeciation. In particular, it is now clear that many fig species host
      two wasp species, so there is more wasp speciation than fig speciation. However,
      little is known about how fig wasps speciate. RESULTS: We studied variation in 71
      fig-pollinating wasps from across the large geographic range of Ficus rubiginosa
      in Australia. All wasps sampled belong to one morphological species
      (Pleistodontes imperialis), but we found four deep mtDNA clades that differed
      from each other by 9-17% nucleotides. As these genetic distances exceed those
      normally found within species and overlap those (10-26%) found between
      morphologically distinct Pleistodontes species, they strongly suggest cryptic fig
      wasp species. mtDNA clade diversity declines from all four present in Northern
      Queensland to just one in Sydney, near the southern range limit. However, at most
      sites multiple clades coexist and can be found in the same tree or even the same
      fig fruit and there is no evidence for parallel sub-division of the host fig
      species. Both mtDNA data and sequences from two nuclear genes support the
      monophyly of the "P. imperialis complex" relative to other Pleistodontes species,
      suggesting that fig wasp divergence has occurred without any host plant shift.
      Wasps in clade 3 were infected by a single strain (W1) of Wolbachia bacteria,
      while those in other clades carried a double infection (W2+W3) of two other
      strains. CONCLUSION: Our study indicates that cryptic fig-pollinating wasp
      species have developed on a single host plant species, without the involvement of
      host plant shifts, or parallel host plant divergence. Despite extensive evidence
      for coevolution between figs and fig wasps, wasp speciation may not always be
      linked strongly with fig speciation.

PMID- 17040563
TI  - Oxidative stress is increased in critically ill patients according to antioxidant
      vitamins intake, independent of severity: a cohort study.
AB  - INTRODUCTION: Critically ill patients suffer from oxidative stress caused by
      reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although
      ROS/RNS are constantly produced under normal circumstances, critical illness can
      drastically increase their production. These patients have reduced plasma and
      intracellular levels of antioxidants and free electron scavengers or cofactors,
      and decreased activity of the enzymatic system involved in ROS detoxification.
      The pro-oxidant/antioxidant balance is of functional relevance during critical
      illness because it is involved in the pathogenesis of multiple organ failure. In
      this study the objective was to evaluate the relation between oxidative stress in
      critically ill patients and antioxidant vitamin intake and severity of illness.
      METHODS: Spectrophotometry was used to measure in plasma the total antioxidant
      capacity and levels of lipid peroxide, carbonyl group, total protein, bilirubin
      and uric acid at two time points: at intensive care unit (ICU) admission and on
      day seven. Daily diet records were kept and compliance with recommended dietary
      allowance (RDA) of antioxidant vitamins (A, C and E) was assessed. RESULTS:
      Between admission and day seven in the ICU, significant increases in lipid
      peroxide and carbonyl group were associated with decreased antioxidant capacity
      and greater deterioration in Sequential Organ Failure Assessment score. There was
      significantly greater worsening in oxidative stress parameters in patients who
      received antioxidant vitamins at below 66% of RDA than in those who received
      antioxidant vitamins at above 66% of RDA. An antioxidant vitamin intake from 66%
      to 100% of RDA reduced the risk for worsening oxidative stress by 94% (ods ratio
      0.06, 95% confidence interval 0.010 to 0.39), regardless of change in severity of
      illness (Sequential Organ Failure Assessment score). CONCLUSION: The critical
      condition of patients admitted to the ICU is associated with worsening oxidative
      stress. Intake of antioxidant vitamins below 66% of RDA and alteration in
      endogenous levels of substances with antioxidant capacity are related to redox
      imbalance in critical ill patients. Therefore, intake of antioxidant vitamins
      should be carefully monitored so that it is as close as possible to RDA.

PMID- 17040564
TI  - The reach of the genome signature in prokaryotes.
AB  - BACKGROUND: With the increased availability of sequenced genomes there have been
      several initiatives to infer evolutionary relationships by whole genome
      characteristics. One of these studies suggested good congruence between genome
      synteny, shared gene content, 16S ribosomal DNA identity, codon usage and the
      genome signature in prokaryotes. Here we rigorously test the phylogenetic signal
      of the genome signature, which consists of the genome-specific relative
      frequencies of dinucleotides, on 334 sequenced prokaryotic genome sequences.
      RESULTS: Intrageneric comparisons show that in general the genomic dissimilarity
      scores are higher than in intraspecific comparisons, in accordance with the
      suggested phylogenetic signal of the genome signature. Exceptions to this trend,
      (Bartonella spp., Bordetella spp., Salmonella spp. and Yersinia spp.), which have
      low average intrageneric genomic dissimilarity scores, suggest that members of
      these genera might be considered the same species. On the other hand, high
      genomic dissimilarity values for intraspecific analyses suggest that in some
      cases (e.g. Prochlorococcus marinus, Pseudomonas fluorescens, Buchnera aphidicola
      and Rhodopseudomonas palustris) different strains from the same species may
      actually represent different species. Comparing 16S rDNA identity with genomic
      dissimilarity values corroborates the previously suggested trend in phylogenetic
      signal, albeit that the dissimilarity values only provide low resolution.
      CONCLUSION: The genome signature has a distinct phylogenetic signal, independent
      of individual genetic marker genes. A reliable phylogenetic clustering cannot be
      based on dissimilarity values alone, as bootstrapping is not possible for this
      parameter. It can however be used to support or refute a given phylogeny and
      resulting taxonomy.

PMID- 17040565
TI  - Reduction of anion reversal potential subverts the inhibitory control of firing
      rate in spinal lamina I neurons: towards a biophysical basis for neuropathic
      pain.
AB  - BACKGROUND: Reduction of the transmembrane chloride gradient in spinal lamina I
      neurons contributes to the cellular hyperexcitability producing allodynia and
      hyperalgesia after peripheral nerve injury. The resultant decrease in anion
      reversal potential (i.e. shift in Eanion to less negative potentials) reduces
      glycine/GABAA receptor-mediated hyperpolarization, but the large increase in
      membrane conductance caused by inhibitory input can nonetheless shunt concurrent
      excitatory input. Without knowing the relative contribution of hyperpolarization
      and shunting to inhibition's modulation of firing rate, it is difficult to
      predict how much net disinhibition results from reduction of Eanion. We therefore
      used a biophysically accurate lamina I neuron model to investigate quantitatively
      how changes in Eanion affect firing rate modulation. RESULTS: Simulations reveal
      that even a small reduction of Eanion compromises inhibitory control of firing
      rate because reduction of Eanion not only decreases glycine/GABAA receptor
      mediated hyperpolarization, but can also indirectly compromise the capacity of
      shunting to reduce spiking. The latter effect occurs because shunting-mediated
      modulation of firing rate depends on a competition between two biophysical
      phenomena: shunting reduces depolarization, which translates into reduced
      spiking, but shunting also shortens the membrane time constant, which translates
      into faster membrane charging and increased spiking; the latter effect
      predominates when average depolarization is suprathreshold. Disinhibition
      therefore occurs as both hyperpolarization- and shunting-mediated modulation of
      firing rate are subverted by reduction of Eanion. Small reductions may be
      compensated for by increased glycine/GABAA receptor-mediated input, but the
      system decompensates (i.e. compensation fails) as reduction of Eanion exceeds a
      critical value. Hyperexcitability necessarily develops once disinhibition becomes
      incompensable. Furthermore, compensation by increased glycine/GABAA receptor
      mediated input introduces instability into the system, rendering it increasingly
      prone to abrupt decompensation and even paradoxical excitation. CONCLUSION:
      Reduction of Eanion dramatically compromises the inhibitory control of firing
      rate and, if compensation fails, is likely to contribute to the allodynia and
      hyperalgesia associated with neuropathic pain. These data help explain the
      relative intractability of neuropathic pain and illustrate how it is important to
      choose therapies not only based on disease mechanism, but based on quantitative
      understanding of that mechanism.

PMID- 17040566
TI  - Technology mediator: a new role for the reference librarian?
AB  - The Arizona Health Sciences Library has collaborated with clinical faculty to
      develop a federated search engine that is useful for meeting real-time clinical
      information needs. This article proposes a technology mediation role for the
      reference librarian that was inspired by the project, and describes the
      collaborative model used for developing technology-mediated services for targeted
      users.

PMID- 17040567
TI  - Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes
      mellitus.
AB  - BACKGROUND: This paper is based on ethnobotanical interviews conducted from 1996
      2000 in Trinidad and Tobago with thirty male and female respondents. METHODS: A
      non-experimental validation was conducted on the plants used for urinary problems
      and diabetes mellitus: This is a preliminary step to establish that the plants
      used are safe or effective, to help direct clinical trials, and to inform
      Caribbean physicians of the plants' known properties to avoid counter
      prescribing. RESULTS: The following plants are used to treat diabetes: Antigonon
      leptopus, Bidens alba, Bidens pilosa, Bixa orellana, Bontia daphnoides, Carica
      papaya, Catharanthus roseus, Cocos nucifera, Gomphrena globosa, Laportea
      aestuans, Momordica charantia, Morus alba, Phyllanthus urinaria and Spiranthes
      acaulis. Apium graviolens is used as a heart tonic and for low blood pressure.
      Bixa orellana, Bontia daphnoides, Cuscuta americana and Gomphrena globosa are
      used for jaundice. The following plants are used for hypertension: Aloe vera,
      Annona muricata, Artocarpus altilis, Bixa orellana, Bidens alba, Bidens pilosa,
      Bonta daphnoides, Carica papaya, Cecropia peltata, Citrus paradisi, Cola nitida,
      Crescentia cujete, Gomphrena globosa, Hibiscus sabdariffa, Kalanchoe pinnata,
      Morus alba, Nopalea cochinellifera, Ocimum campechianum, Passiflora
      quadrangularis, Persea americana and Tamarindus indicus. The plants used for
      kidney problems are Theobroma cacao, Chamaesyce hirta, Flemingia strobilifera,
      Peperomia rotundifolia, Petiveria alliacea, Nopalea cochinellifera, Apium
      graveolens, Cynodon dactylon, Eleusine indica, Gomphrena globosa, Pityrogramma
      calomelanos and Vetiveria zizanioides. Plants are also used for gall stones and
      for cooling. CONCLUSION: Chamaesyce hirta, Cissus verticillata, Kalanchoe
      pinnata, Peperomia spp., Portulaca oleraceae, Scoparia dulcis, and Zea mays have
      sufficient evidence to support their traditional use for urinary problems,
      "cooling" and high cholesterol. Eggplant extract as a hypocholesterolemic agent
      has some support but needs more study. The plants used for hypertension, jaundice
      and diabetes that may be safe and justify more formal evaluation are Annona
      squamosa, Aloe vera, Apium graveolens, Bidens alba, Carica papaya, Catharanthus
      roseus, Cecropia peltata, Citrus paradisi, Hibsicus sabdariffa, Momordica
      charantia, Morus alba, Persea americana, Phyllanthus urinaria, Tamarindus indicus
      and Tournefortia hirsutissima. Several of the plants are used for more than one
      condition and further trials should take this into account.

PMID- 17040568
TI  - Activin B can signal through both ALK4 and ALK7 in gonadotrope cells.
AB  - BACKGROUND: Activins stimulate pituitary FSH synthesis via transcriptional
      regulation of the FSHbeta subunit gene (Fshb). Like other members of the TGFbeta
      superfamily, these ligands signal through complexes of type I and type II
      receptor serine/threonine kinases. The type I receptors, or activin receptor-like
      kinases (ALKs), propagate intracellular signals upon ligand binding and
      phosphorylation by associated type II receptors. ALK4 is generally regarded as
      the type I receptor for activins; however, recent data suggested that activin B
      and AB might also signal through ALK7. Here, we examined a role for ALK7 in
      activin B-regulated Fshb transcription. METHODS: We analyzed ALK7 mRNA expression
      in immortalized gonadotrope cells, LbetaT2, and adult murine pituitary by RT-PCR.
      We next transfected LbetaT2 cells with wild-type and kinase-deficient (Lys to
      Arg, KR) forms of ALK4 and ALK7 and examined the effects of these receptors on
      activin A and B stimulated Fshb promoter-reporter activity. Cells were also
      transfected with constitutively active (Thr to Asp, TD) forms of the receptors
      and their effects on endogenous Fshb mRNA levels and phosphorylation of
      transfected Smad2/3 were measured by RT-PCR and Western blot, respectively.
      Finally, we measured ALK4(TD) and ALK7(TD) stimulation of Fshb transcription when
      endogenous Smad3 levels were depleted using short hairpin RNAs. RESULTS: ALK7
      mRNA was expressed in LbetaT2 cells and pituitary gland. Transfection of ALK4
      cDNA potentiated the effects of both activin A and activin B on Fshb promoter
      reporter activity in LbetaT2 cells. In contrast, ALK7 transfection selectively
      potentiated activin B's effects. Transfection of ALK4(KR) and ALK7(KR) partly
      inhibited basal and activin B-stimulated reporter activity, whereas ALK4(TD) and
      ALK7(TD) potently stimulated the Fshb promoter and endogenous mRNA levels.
      Transfection of both ALK4(TD) and ALK7(TD) stimulated Smad2/3 phosphorylation,
      and the effects of both receptors on Fshb promoter activity were inhibited by
      depletion of endogenous Smad3 protein levels. CONCLUSION: These data suggest that
      immortalized gonadotropes express ALK7 and that activin B can signal through this
      receptor to stimulate Fshb transcription. The relative roles of endogenous ALK4
      and ALK7 receptors in mediating activin B's effects in these cells have yet to be
      determined.

PMID- 17040569
TI  - Living with primary ciliary dyskinesia: a prospective qualitative study of
      knowledge sharing, symptom concealment, embarrassment, mistrust, and stigma.
AB  - BACKGROUND: Primary ciliary dyskinesia (PCD) is a chronic respiratory disease for
      which there is little psycho-social research and no qualitative studies of
      individuals living with the condition. A questionnaire-based survey in 2003 found
      evidence of stigmatisation in some individuals with PCD. Although the
      questionnaire had face and construct validity, stigmatisation was not cross
      validated against interviews. The present study had the twin aims of carrying out
      a qualitative study of the adult patients living with PCD, and using a structured
      design to validate the questionnaire measure of stigma. METHODS: Interviews were
      carried out with six pairs of individuals with PCD, matched for sex, situs, and
      age, one with a high stigma score in 2003 and the other with a low stigma score.
      Depth-qualitative interviews were conducted by one author to explore themes
      surrounding the psycho-social impact of PCD using a grounded theory analysis. The
      interviewer was blind to the stigma scores of participants, and after the
      qualitative analysis was completed, the interviewer made an assessment of which
      member of each pair seemed the more stigmatised, after which the code was broken.
      RESULTS: Interviews revealed a number of themes, including other people's
      knowledge of PCD, the sharing of knowledge about PCD, the concealment of symptoms
      of PCD, embarrassment at symptoms, changes of behaviour in response to PCD,
      mistrust of medical care, in particular in relation to problems in diagnosis, a
      mistrust of general practitioners who were seen as poorly informed, and the
      importance of expert care at tertiary referral centres. Although stigmatisation
      as such was rarely mentioned directly by respondents, when the interviewer's
      judgement on level of stigmatisation was correlated with stigma scores from 2003,
      it was found that the more stigmatised member had been correctly identified in
      all six pairs (p = .016). CONCLUSION: Our results suggest that some people with
      PCD feel isolated through mistrust in medicine, and lack of knowledge surrounding
      PCD. Many responses to PCD can be explained in terms of stigmatisation, and in
      particular felt stigma. The correlation between questionnaire used several years
      previously, and the interviewer's judgements of stigmatisation suggest that the
      stigma questionnaire had both predictive validity and long-term stability. As in
      other chronic conditions, stigmatisation occurs only in some individuals with
      PCD, and the present study explores the basis of stigmatisation, and validate the
      questionnaire as a measure of difference in stigma.

PMID- 17040570
TI  - Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13,
      12p13, 17q12, and 20q13 amplifications in breast cancers.
AB  - BACKGROUND: Oncogene amplification and overexpression occur in tumor cells.
      Amplification status may provide diagnostic and prognostic information and may
      lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12
      and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the
      frequencies and clinical impact of amplifications, we analyzed 547 invasive
      breast tumors organized in a tissue microarray (TMA) by fluorescence in situ
      hybridization (FISH) and calculated correlations with histoclinical features and
      prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on
      RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1;
      (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on
      MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with
      MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification
      of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in
      19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%,
      and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The
      8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most
      frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%),
      20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found
      amplified alone. The most frequent co-amplification was 8p12/11q13.
      Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification
      of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results
      establish the frequencies, prognostic impacts and subtype associations of various
      amplifications and co-amplifications in breast cancers.

PMID- 17040572
TI  - Antithrombin significantly influences platelet adhesion onto immobilized
      fibrinogen in an in-vitro system simulating low flow.
AB  - BACKGROUND: Adhesion of platelets onto immobilized fibrinogen is of importance in
      initiation and development of thrombosis. According to a recent increase in
      evidence of a multiple biological property of antithrombin, we evaluated the
      influence of antithrombin on platelet adhesion onto immobilized fibrinogen using
      an in-vitro flow system. METHODS: Platelets in anticoagulated whole blood (29
      healthy blood donors) were labelled with fluorescence dye and perfused through a
      rectangular flow chamber (shear rates of 13 s-1 to 1500 s-1). Platelet adhesion
      onto fibrinogen-coated slips was assessed using a fluorescence laser-scan
      microscope and compared to the plasma antithrombin activity. Additionally the
      effect of supraphysiological AT supplementation on platelets adhesion rate was
      evaluated. RESULTS: Within a first minute of perfusion, an inverse correlation
      between platelet adhesion and plasma antithrombin were observed at 13 s-1 and 50
      s-1 (r = -0.48 and r = -0.7, p < 0.05, respectively). Significant differences in
      platelet adhesion related to low (92 +/- 3.3%) and high (117 +/- 4.1%)
      antithrombin activity (1786 +/- 516 U vs. 823 +/- 331 U, p < 0.05) at low flow
      rate (13 s-1, within first minute) have been found. An in-vitro supplementation
      of whole blood with antithrombin increased the antithrombin activity up to 280%
      and platelet adhesion rate reached about 65% related to the adhesion rate in a
      non-supplemented blood (1.25 +/- 0.17 vs. 1.95 +/- 0.4 p = 0.008, respectively).
      CONCLUSION: It appears that antithrombin in a low flow system suppresses platelet
      adhesion onto immobilized fibrinogen independently from its antithrombin
      activity. A supraphysiological substitution of blood with antithrombin
      significantly reduces platelet adhesion rate. This inhibitory effect might be of
      clinical relevance.

PMID- 17040571
TI  - Health-related quality of life of Canadian children and youth prenatally exposed
      to alcohol.
AB  - BACKGROUND: In Canada, the incidence of Fetal Alcohol Spectrum Disorder (FASD)
      has been estimated to be 1 in 100 live births. Caused by prenatal exposure to
      alcohol, FASD is the leading cause of neuro-developmental disabilities among
      Canadian children, and youth. OBJECTIVE: To measure the health-related quality of
      life (HRQL) of Canadian children and youth diagnosed with FASD. METHODS: A
      prospective cross-sectional study design was used. One-hundred and twenty-six
      (126) children and youth diagnosed with FASD, aged 8 to 21 years, living in urban
      and rural communities throughout Canada participated in the study. Participants
      completed the Health Utilities Index Mark 3 (HUI3). HUI3 measures eight health
      attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition,
      and pain. Utilities were used to measure a single cardinal value between 0 and
      1.0 (0 = all-worst health state; 1 = perfect health) to reflect the global HRQL
      for that child. Mean HRQL scores and range of scores of children and youth with
      FASD were calculated. A one-sample t-test was used to compare mean HRQL scores of
      children and youth with FASD to those from the Canadian population. RESULTS: Mean
      HRQL score of children and youth with FASD was 0.47 (95% CI: 0.42 to 0.52) as
      compared to a mean score of 0.93 (95% CI: 0.92 to 0.94) in those from the general
      Canadian population (p < 0.001). Children demonstrated moderate to severe
      dysfunction on the single-attributes of cognition and emotion. CONCLUSION:
      Children and youth with FASD have significantly lower HRQL than children and
      youth from the general Canadian population. This finding has significant
      implications for practice, policy development, and research.

PMID- 17040573
TI  - Rural-urban differentials of premature mortality burden in south-west China.
AB  - BACKGROUND: Yunnan province is located in south western China and is one of the
      poorest provinces of the country. This study examines the premature mortality
      burden from common causes of deaths among an urban region, suburban region and
      rural region of Kunming, the capital of Yunnan. METHODS: Years of life lost (YLL)
      rate per 1,000 and mortality rate per 100,000 were calculated from medical death
      certificates in 2003 and broken down by cause of death, age and gender among
      urban, suburban and rural regions. YLL was calculated without age-weighting and
      discounting rate. Rates were age-adjusted to the combined population of three
      regions. However, 3% discounting rate and a standard age-weighting function were
      included in the sensitivity analysis. RESULTS: Non-communicable diseases
      contributed the most YLL in all three regions. The rural region had about 50%
      higher premature mortality burden compared to the other two regions. YLL from
      infectious diseases and perinatal problems was still a major problem in the rural
      region. Among non-communicable diseases, YLL from stroke was the highest in the
      urban/suburban regions; COPD followed as the second and was the highest in the
      rural region. Mortality burden from injuries was however higher in the rural
      region than the other two regions, especially for men. Self-inflicted injuries
      were between 2-8 times more serious among women. The use of either mortality rate
      or YLL gives a similar conclusion regarding the order of priority. Reanalysis
      with age-weighting and 3% discounting rate gave similar results. CONCLUSION:
      Urban south western China has already engaged in epidemiological pattern of
      developed countries. The rural region is additionally burdened by diseases of
      poverty and injury on top of the non-communicable diseases.

PMID- 17040574
TI  - Passive immunoprophylaxis and therapy with humanized monoclonal antibody specific
      for influenza A H5 hemagglutinin in mice.
AB  - BACKGROUND: Highly pathogenic avian H5N1 influenza virus is a major public health
      concern. Given the lack of effective vaccine and recent evidence of antiviral
      drug resistance in some isolates, alternative strategies for containment of a
      possible future pandemic are needed. Humanized monoclonal antibodies (mAbs) that
      neutralize H5N1 virus could be used as prophylaxis and treatment to aid in the
      containment of such a pandemic. METHODS: Neutralizing mAbs against H5
      hemagglutinin were humanized and introduced into C57BL/6 mice (1, 5, or 10 mg/kg
      bodyweight) one day prior to-, one day post- and three days post-lethal challenge
      with H5N1 A/Vietnam/1203/04 virus. Efficacy was determined by observation of
      weight loss as well as survival. RESULTS: Two mAbs neutralizing for antigenically
      variant H5N1 viruses, A/Vietnam/1203/04 and A/Hong Kong/213/03 were identified
      and humanized without loss of specificity. Both antibodies exhibited prophylactic
      efficacy in mice, however, VN04-2-huG1 performed better requiring only 1 mg/kg
      bodyweight for complete protection. When used to treat infection VN04-2-huG1 was
      also completely protective, even when introduced three days post infection,
      although higher dose of antibody was required. CONCLUSION: Prophylaxis and
      treatment using neutralizing humanized mAbs is efficacious against lethal
      challenge with A/Vietnam/1203/04, providing proof of principle for the use of
      passive antibody therapy as a containment option in the event of pandemic
      influenza.

PMID- 17040575
TI  - Analysis of role-play in medical communication training using a theatrical device
      the fourth wall.
AB  - BACKGROUND: Communication training is a central part of medical education. The
      aim of this article is to explore the positions and didactic functions of the
      fourth wall in medical communication training, using a role-play model basically
      similar to a theatrical performance. METHOD: The empirical data stem from a
      communication training model demonstrated at an international workshop for
      medical teachers and course organizers. The model involves an actress playing a
      patient, students alternating in the role of the doctor, and a teacher who
      moderates. The workshop was videotaped and analyzed qualitatively. RESULTS: The
      analysis of the empirical material revealed three main locations of the fourth
      wall as it moved and changed qualities during the learning session: 1) A
      traditional theatre location, where the wall was transparent for the audience,
      but opaque for the participants in the fiction. 2) A "timeout/reflection"
      location, where the wall was doubly opaque, for the patient on the one side and
      the moderator, the doctor and the audience on the other side and 3) an
      "interviewing the character" location where the wall enclosed everybody in the
      room. All three locations may contribute to the learning process. CONCLUSION: The
      theatrical concept 'the fourth wall' may present an additional tool for new
      understanding of fiction based communication training. Increased understanding of
      such an activity may help medical teachers/course organizers in planning and
      evaluating communication training courses.

PMID- 17040576
TI  - Adenocarcinoma of the caecum metastatic to the bladder: an unusual cause of
      haematuria.
AB  - BACKGROUND: Primary malignancies of colorectal origin can metastasise to the
      bladder. Reports are however extremely rare, particularly from the caecum. CASE
      REPORT: The report describes the case of a 45-year old male with Duke's B caecal
      carcinoma treated with a laparoscopically-assisted right hemicolectomy and
      adjuvant 5-Fluorouracil chemotherapy. Subsequently, a metastatic lesion to the
      bladder was demonstrated and successfully excised by partial cystectomy.
      CONCLUSION: In order that optimal therapeutic options can be determined, it is
      important for clinicians to distinguish between primary disease of the bladder
      and other causes of haematuria. Various immunohistochemical techniques attempt to
      differentiate primary adenocarcinoma of the bladder from secondary colorectal
      adenocarcinoma. Suspicion of metastatic disease must be raised when
      histologically unusual bladder tumours are identified.

PMID- 17040577
TI  - Circulating immune complexes and trace elements (Copper, Iron and Selenium) as
      markers in oral precancer and cancer : a randomised, controlled clinical trial.
AB  - AIM: To evaluate the levels of circulating immune complexes, trace elements
      (copper, iron and selenium) in serum of patients with oral submucous fibrosis
      (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the
      alteration and identify the best predictors amongst these parameters for disease
      occurrence and progression. METHODS: Circulating immune complexes (CIC) were
      estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum
      estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl
      Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse
      Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed
      increased circulating immune complex levels in the precancer and cancer patients.
      Serum copper levels showed gradual increase from precancer to cancer patients.
      However, serum iron levels were decreased significantly in the cancer group.
      Selenium levels showed marked decrease in the cancer group. Among CIC, serum,
      copper, iron and selenium the best predictors for the occurrence of lesions were
      age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The
      present study shows that these immunological and biological markers may be
      associated with the pathogenesis of oral premalignant and malignant lesions and
      their progressions. Concerted efforts would, therefore, help in early detection,
      management, and monitoring the efficacy of treatment.

PMID- 17040578
TI  - Molecular basis of inherited skin-blistering disorders, and therapeutic
      implications.
AB  - Epidermolysis bullosa (EB) and associated skin-fragility syndromes are a group of
      inherited skin diseases characterised by trauma-induced blistering of the skin
      and mucous membranes. Mutations in at least 14 distinct genes encoding molecular
      components of the epidermis or the dermal-epidermal junction (DEJ) can cause
      blistering skin diseases that differ by clinical presentation and severity of the
      symptoms. Despite great advances in discerning the genetic basis of this group of
      diseases, the molecular pathways leading to symptoms are not yet fully
      understood. Unravelling these pathways by molecular analysis of the structure and
      in vitro assessment of functional properties of the human proteins involved,
      combined with genetic models in lower organisms, should pave the way for specific
      cures for inherited skin fragility.

PMID- 17040579
TI  - Tornwaldt's cyst formation after concurrent chemoradiotherapy for nasopharyngeal
      carcinoma.
AB  - The complications of concurrent chemoradiotherapy for nasopharyngeal carcinoma
      include dryness of mouth, sensorineural hearing loss, dental caries, trismus,
      pituitary dysfunction, myelitis, paralysis of cranial nerves IX-XII, massive neck
      fibrosis and pharyngeal wall necrosis. Tornwaldt's cyst formation after
      concurrent chemoradiotherapy for nasopharyngeal carcinoma has not been reported
      previously in the world literature. Tornwaldt's cyst, a persistent pharyngeal
      bursa, is found in about 3 per cent of the adult population, although the
      majority of these are asymptomatic. We describe the previously unreported
      complication of Tornwaldt's cyst formation after concurrent chemoradiotherapy for
      nasopharyngeal carcinoma.

PMID- 17040580
TI  - Long-term outcomes of laser-assisted uvulopalatoplasty in 168 patients with
      snoring.
AB  - Laser-assisted uvulopalatoplasty (LAUP) is an established treatment for snoring.
      Our institution has been using a modification of the Kamami technique since 1995.
      Between January 1995 and December 2001, 469 patients underwent LAUP for snoring.
      A telephone survey of these patients and their partners was conducted
      retrospectively. One hundred and sixty-eight patients and their partners were
      interviewed and the findings analysed.Of the 168 patients, 122 had LAUP alone, 42
      had LAUP and tonsillectomy and four had LAUP and septoplasty. The median follow
      up time was 59 months (range 19 to 98 months).Seventy-four per cent reported
      improvement at six weeks, 69 per cent reported improvement at nine months and 55
      per cent reported improvement at the time of interview. To assess the degree of
      improvement, patients and their partners were asked to grade any improvement in
      percentage terms. The mean subjective improvement scores were 57 per cent at six
      weeks (95 per cent confidence interval (CI) 50-64 per cent), 45 per cent at nine
      months (95 per cent CI 38-59 per cent) and 30 per cent at the time of interview
      (95 per cent CI 23-35 per cent). Patients who reported weight gain since surgery
      did not have a poorer outcome than those who reported no weight change or weight
      loss. Neither did weight loss predict a better outcome. The procedure was
      generally well tolerated, with only 30 patients (18 per cent) reporting
      complications (mainly minor). The benefits of LAUP wane with time and the results
      are best in the first 12 months following surgery. Our study suggests that 55 per
      cent of patients selected after sleep studies and sleep nasendoscopy will enjoy
      long-term benefit.

PMID- 17040581
TI  - Angina masquerading as sinusitis.
AB  - Facial pain of cardiac origin is rare. There are several references in the world
      literature to angina referred to the teeth and the mandible. This report
      describes a patient with facial pain which was thought to be of sinus origin and
      which was relieved by coronary stenting.

PMID- 17040582
TI  - Otolaryngological requirements for recreational self-contained underwater
      breathing apparatus (SCUBA) diving.
AB  - Recreational self-contained underwater breathing apparatus (SCUBA) diving
      continues to grow in popularity. Medical requirements to be 'fit to dive' vary
      throughout the world, from self-certification to a full medical examination prior
      to training. This review discusses the relative merits of the most commonly used
      guidelines for recreational SCUBA diving, with reference to common diving-related
      otorhinolaryngological conditions. Areas of controversy, such as fitness to dive
      after rhinological and otological surgery, are discussed. The authors suggest
      that a unified approach from the various recreational SCUBA diving organizations
      involved would aid in clarification for divers and physicians alike. The
      difficulties in achieving such a unified approach, however, should not be
      underestimated.

PMID- 17040583
TI  - Spinal accessory nerve function after neck dissections.
AB  - The aim of this study was to evaluate spinal accessory nerve function after
      functional neck dissection (FND) and radical neck dissection (RND) by monitoring
      the nerve with electromyographic (EMG) examinations. A prospective, double-blind,
      clinical study was undertaken in 21 patients (42 neck side dissections) operated
      on for head and neck malignant diseases, separated into two groups: 10 neck sides
      in the RND group and 32 neck sides in the FND group. Electromyographic
      examinations were performed pre-operatively and post-operatively in the third
      week and third and ninth months. Additionally, a questionnaire, modified from the
      neck dissection impairment index, was applied to all the patients in order to
      assess shoulder function in the ninth post-operative month. All patients had
      maximum EMG scores pre-operatively. Following the operation, motor amplitudes
      decreased in both groups. At the third post-operative month, amplitudes decreased
      to their lowest values. As expected, the decreases in amplitude and EMG score
      were more prominent in the RND group. Following reinnervation, the amplitudes of
      the trapezius motor response increased in the FND group but never reached pre
      operative values (during the time of follow up). The FND group scores for pain,
      neck and shoulder stiffness, and disability in heavy object lifting, light object
      lifting and reaching overhead were significantly lower than those of the RND
      group. In FND, one aims to preserve anatomically the spinal accessory nerve, and
      it is presumed to be intact after the procedure. However, using EMG nerve
      function monitoring, our study revealed that profound spinal nerve injury was
      detected immediately after FND surgery, which tended to improve over subsequent
      months but had not regained its original function by the end of the ninth post
      operative month.

PMID- 17040584
TI  - Multifocal bigerminal mature teratomas of the head and neck.
AB  - Teratomas and dermoids or hairy polyps of the head and neck are rare congenital
      tumours, often confused and reported to appear as single masses, that may cause
      upper aerodigestive tract impairment. Their histological classification, origin
      and embryological basis of development have been a topic of debate in the past
      and recent literature. We report a case of an infant presenting with a multifocal
      bigerminal teratoma in the nasopharynx and the neck, causing a deep neck
      infection, and discuss the unique clinicopathological aspects of this case.

PMID- 17040585
TI  - A multivariate analysis of the factors predicting hearing outcome after surgery
      for cholesteatoma in children.
AB  - OBJECTIVE: To explore factors influencing hearing outcomes in children treated by
      canal wall up (CWU) and canal wall down (CWD) mastoid surgery. METHODS:
      Retrospective cohort study including three units in Bristol and Bath, UK. Ninety
      consecutive children underwent cholesteatoma mastoid surgery, with the first
      procedure between 1998 and 2001; minimum follow up was three disease-free years.
      RESULTS: The CWU and CWD cohorts significantly differed in pre-operative stage
      and hearing. After disease eradication, air conduction (AC) thresholds changed by
      +4.0 dB (95 per cent confidence intervals (95% CI) -2.0, 10.1) in the CWD group
      and -5.3 dB (95% CI -9.3, 1.3) in the CWU group (p=0.029). Using multiple linear
      regression to account for cohort differences, AC thresholds were increased by:
      pre-operative AC threshold (p<0.0001), initial ossicular stage (p=0.013), and CWD
      surgery (p=0.005). CONCLUSION: Disease-free hearing was better with CWU-surgery,
      less initial ossicular damage, and better pre-operative hearing. Worse initial
      disease increased the likelihood of CWD surgery. Wider use of ossiculoplasty in
      the CWU cohort (51 per cent vs 5 per cent) may partially explain the superior
      results.

PMID- 17040586
TI  - Pneumosinus dilatans: demonstrated by sinus expansion on serial sinus X-rays with
      discussion of possible aetiology.
AB  - A case of pneumosinus dilatans of the frontal sinus is presented. The findings on
      serial skull X-rays, performed on three occasions over a 10-year period, seem to
      support a developmental aetiology for this rare condition.

PMID- 17040587
TI  - Can we improve dysphagia referrals?
AB  - We set out to examine whether a multidisciplinary out-patient dysphagia referral
      triage service would shorten the duration of a patient's referral process and
      direct patients to the correct specialty. A review was carried out of patients
      referred with dysphagia before and after the introduction of a multidisciplinary
      out-patient dysphagia service, from February 2001 to April 2001 and from January
      2002 to March 2002, inclusive. One hundred and eight patients were referred in
      total. The length of time until the first appointment was reduced from four to
      three weeks (median; range one to 23; p<0.001). The number of instrumental
      investigations was reduced, with a median of one instrumentation per patient
      under the new service, compared with two in those under the standard service
      (p<0.001). Attendance to hospital was also reduced, with 45 per cent of patients
      under the new service requiring only one appointment, compared with 13 per cent
      in those under the standard service (p<0.001). The multidisciplinary out-patient
      dysphagia service was associated with significant reductions in waiting times, in
      the number of instrumental investigations and in the duration of the patient's
      referral process.

PMID- 17040588
TI  - Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate
      in acute sensorineural hearing loss.
AB  - Patients with autoimmune inner-ear disease (AIED) are treated with high doses of
      steroids in the short term when suffering an acute hearing loss. As a
      consequence, substances such as methotrexate have been employed in the role of
      steroid-sparing agents. Additionally, it is known that tumour necrosis factor
      alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition
      of which may be of benefit in AIED. This case report illustrates the use of a
      TNFalpha inhibitor in combination with methotrexate, which is known to be an
      effective combination in rheumatoid arthritis but has yet to be described for
      sensorineural hearing loss. We conclude that progressive AIED may respond well to
      TNFalpha inhibition, whilst more difficult cases, such as this example, could
      benefit from combining such therapy with methotrexate.

PMID- 17040589
TI  - Timing of co-phenylcaine administration before rigid nasendoscopy: a randomized,
      controlled trial.
AB  - Rigid nasendoscopy is a commonly used method of examining the nasal cavity and
      postnasal space. Co-phenylcaine is useful for its vasoconstrictive and
      anaesthetic properties, but the length of time allowed for it to take effect is
      variable. We performed a single-blind, randomized, controlled trial to determine
      whether it was better to allow one or 10 minutes for co-phenylcaine to take
      effect. Fifty patients were randomized into two groups, 25 in each. Patients in
      the 10 minute group experienced less discomfort (p=0.02) and less pain (p=0.018)
      than those in the one minute group. Ease of examination was also greater in the
      10 minute group, as was the quality of the image obtained (p<0.001).

PMID- 17040590
TI  - Role of mitomycin C in reducing adhesion formation following endoscopic sinus
      surgery.
AB  - OBJECTIVE: To study the role of mitomycin C in reducing adhesion formation
      following endoscopic sinus surgery. STUDY DESIGN: Prospective, randomized,
      controlled trial. SETTING: Tertiary care referral centre. PATIENTS: Thirty
      patients were selected suffering long-term problems with bilateral chronic
      rhinosinusitis, with no relief obtained from medical therapy. Patients requiring
      revision sinus surgery or having acute upper respiratory tract infection were
      excluded. INTERVENTIONS: Diagnostic nasal endoscopies and non-contrast
      computerized tomography of nose and paranasal sinuses were undertaken and,
      following confirmation of the diagnosis, functional endoscopic sinus surgery
      (FESS) was carried out bilaterally using the Messerklinger technique. On
      completion of the surgery, a cotton wick soaked in mitomycin C was placed in one
      or other side of the nose in the middle meatus. Follow up was for three months
      and patients were assessed for subjective and objective improvement in their
      symptoms. RESULTS: Post-operatively, of the 11 (36.6 per cent) patients
      complaining of persistent nasal obstruction, nine had complaints limited to the
      control side only (p=0.005). Out of the nine (30 per cent) patients complaining
      of recurrent nasal discharge, eight had complaints on the control side and only
      one reported discharge from both sides (p=0.006). CONCLUSION: Mitomycin C may be
      topically applied in post-operative FESS cases to reduce adhesion formation and
      hence the need for revision surgery.

PMID- 17040591
TI  - Surgical management of only hearing ears with positive indications.
AB  - Positive surgical indications for an only hearing ear were evaluated in order to
      improve patients' quality of life. Fifteen cases of surgery involving an only
      hearing ear over the past eight years were retrospectively reviewed. Of eight
      perforated chronic otitis media cases, seven underwent type one tympanoplasty and
      one underwent simple underlay myringoplasty regardless of otorrhoea at the time
      of surgery. Of six cholesteatoma cases, two received the canal wall up method and
      four received the canal wall down method. Ossiculoplasty was carefully performed
      in six cases. Hearing was improved in seven cases, whereas it remained unchanged
      in seven cases and deteriorated in one case. Of nine patients, two did not need a
      hearing aid after surgery. Five patients with severe combined hearing loss (>90
      dB) were able to communicate with a hearing aid, alleviating their anxiety
      regarding hearing loss. Only hearing ears with chronic otitis media and
      cholesteatoma can be successfully treated by tympanoplasty with or without
      ossiculoplasty.

PMID- 17040592
TI  - Role of information leaflets in improving the practice of informed consent for
      patients undergoing septoplasty.
AB  - AIM: To evaluate the effectiveness of an information leaflet in improving patient
      understanding of the procedure and complications of septoplasty. DESIGN: The
      baseline knowledge of a group of patients who had attended a pre-assessment
      clinic prior to septoplasty was assessed. The procedure and its complications
      were then verbally explained. The patients' knowledge was then re-assessed on the
      morning of surgery and any improvements noted. In the second arm of the study, an
      information leaflet was introduced at the time of verbal instruction and any
      differences in improvement in knowledge were assessed. RESULTS: Data from the two
      groups were analysed using an analysis of covariance with differences in baseline
      (pre-instruction) knowledge controlled. Additional improvements in mean recall
      score following leaflet distribution were highly statistically significant when
      compared with mean recall in the control group (p<0.001). CONCLUSION: The use of
      information leaflets increases patients' knowledge about a surgical procedure and
      its potential complications.

PMID- 17040593
TI  - Investigation of interleukin 10, 12 and 18 levels in patients with head and neck
      cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial
      malignancy. It is the most common neoplasm arising in the upper aerodigestive
      tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour
      activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin
      10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive
      activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types
      of cancer have shown that the level of IL-12 in serum or tissues is suppressed
      and/or the IL-10 level is increased, suggesting that there is an impaired cell
      mediated anti-tumour response. The aim of this study was to measure pre-operative
      serum cytokine concentrations in HNSCC patients in order to detect any changes in
      IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship
      between cytokine levels and standard clinicopathological features, including
      tumour site, tumour stage and presence of nodal metastasis, was also examined.
      Fifty-seven patients with primary HNSCC were prospectively recruited, together
      with 40 non-tumour control patients with a similar age and sex distribution.
      Serum cytokine levels were measured using commercial quantitative enzyme-linked
      immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels
      (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml,
      37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10
      levels than were controls, as IL-10 was positive in 27/55 patients but in only
      9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to
      primary site, being more commonly observed in hypopharyngeal and laryngeal
      tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3
      and T4). No differences in IL-18 levels were observed between patients and
      controls (p=0.169). These results suggest (in agreement with studies on other
      solid malignancies) that HNSCC causes a significant change in the serum levels of
      specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely
      to promote an effective cell-mediated anti-tumour response.

PMID- 17040594
TI  - Idiopathic maxillary antral mucocele in a child: a rare presentation.
AB  - We report a case of a large maxillary sinus mucocele in a 14-year-old girl
      presenting with epiphora, proptosis and dental pain. This was marsupialized
      endoscopically, with complete resolution of symptoms over three months' follow
      up. The literature is reviewed.

PMID- 17040595
TI  - Departmental audit of tonsillectomy haemorrhage rates: pitfalls in
      interpretation.
AB  - Concerns that a largely anecdotal increase in post tonsillectomy haemorrhage
      rates was related to the introduction of disposable instruments have prompted
      much investigation. The result has been, rather, to highlight other variables
      influencing this risk, but especially to insist on the following: 1. Training in
      traditional 'cold' techniques. 2. Regular departmental audit of haemorrhage
      rates. 3. Presentation of such data to patients to ensure informed consent. This
      audit demonstrates the pitfalls in interpretation of crude data, unadjusted for
      case-mix, in predicting individual patient risk and in national ranking of unit
      performance.

PMID- 17040596
TI  - Laryngeal cancer after topical mitomycin C application.
AB  - Mitomycin C is part of the mitomycin group of antibiotics and has found use in
      medicine in the treatment of various cancers, including those of the head and
      neck. In recent years, it has gained popularity as a topical treatment to prevent
      scar formation in the larynx and choanae in paediatric and adult inflammatory
      processes. Also, this alkylating agent is potentially a potent carcinogen. We
      report the first case in the world literature of laryngeal carcinoma in a non
      smoking adult, which may have been induced by topical mitomycin C application to
      a glottic web. We discuss the mechanism of action of this drug, and we advise
      caution on its use for benign laryngeal pathologies.

PMID- 17040597
TI  - Tinnitus and Paget's disease of bone.
AB  - AIM: To investigate the prevalence of tinnitus and deafness in subjects with
      Paget's disease of bone. MATERIALS AND METHODS: One hundred and thirty-four
      subjects in total (77 with Paget's disease) were identified and audiologically
      examined. Subjects' experience of tinnitus was surveyed via a questionnaire and
      the results compared with those of age-matched controls. RESULTS: Hearing loss in
      those with Paget's disease of bone was significantly worse than in controls.
      Hearing handicap was also much worse in the Paget's subjects. Sixty-one per cent
      of the Paget's subjects suffered from tinnitus, compared with 36 per cent of the
      controls. CONCLUSION: Deafness is a recognized, common sequelae of Paget's
      disease of bone, and tinnitus is a common accompanying symptom.

PMID- 17040598
TI  - Prospective study of the microbiological flora of hearing aid moulds and the
      efficacy of current cleaning techniques.
AB  - INTRODUCTION: Wearing hearing aid earmoulds has been implicated as a predisposing
      factor in the development of chronic otitis externa. Audiologists come into
      contact with a large number of hearing aid earmoulds and these could potentially
      harbour pathogenic micro-organisms, with the risk of subsequent cross infection.
      Cleaning with dilute alcohol is widely used in an attempt to break the chain of
      infection. OBJECTIVE: To determine the presence and nature of microbial flora on
      hearing aid earmoulds and the efficacy of cleaning methods used to prevent cross
      infection. SETTING: Secondary health care within the audiology department of
      Addenbrooke's Hospital, Cambridge, UK. DESIGN: A prospective, observational
      study. METHODS: Hearing aid earmoulds were swabbed before and after cleaning.
      Samples were cultured to determine qualitatively and quantitatively the
      microbiological flora present before and after cleaning. RESULTS: Twenty out of
      21 (95 per cent) earmoulds had microbes present and, of these, 19/20 (95 per
      cent) had a polymicrobial profile. Coagulase negative staphylococci and
      diphtheroids were the most frequent microbial isolates, but pathogenic bacteria
      and fungi were also demonstrated on earmoulds both before and after cleaning.
      CONCLUSIONS: The polymicrobial flora, including recognized pathogens, that
      colonizes earmoulds may lead to chronic otitis externa. Cleaning with 70 per cent
      alcohol solution was ineffective, in particular for pathogenic fungi on
      earmoulds.

PMID- 17040599
TI  - Anaplastic thyroid carcinoma implantation after fine needle aspiration cytology.
AB  - We report the case of a 59-year-old man with a two-month history of a fast
      growing, left-sided neck mass and a 5 mm nodule over a thyroid mass at the site
      of fine needle aspiration cytology performed four weeks earlier.
      Histopathological studies confirmed anaplastic carcinoma of the thyroid and
      cutaneous needle track seeding of the primary tumour. The patient succumbed to
      extensive disease 10 weeks after initial diagnosis. To our knowledge, this is a
      rare report of implantation of anaplastic thyroid carcinoma along the track of
      fine needle aspiration. Some factors involved in needle track seeding are: needle
      size; number of passes; withdrawing the needle without releasing suction;
      injecting the tumour at time of biopsy; and inherent characteristics of the
      lesion (e.g. number of cells dislodged, adhesiveness of cells, amount of stroma
      present, enzymes released and immunologic characteristics).

PMID- 17040600
TI  - Pre-vertebral surgical emphysema following functional endoscopic sinus surgery.
AB  - Functional endoscopic sinus surgery (FESS) is a widely practiced technique in the
      UK. This procedure has variable complication rates and can have some serious
      consequences. We present a case of surgical emphysema of the neck, face and the
      pre-vertebral space following FESS. Emphysema of the face and neck has been
      previously reported. However, to our knowledge, emphysema of the pre-vertebral
      space following FESS has not been documented. Pre-vertebral emphysema following
      FESS is an unusual and potentially serious complication.

PMID- 17040601
TI  - Radiofrequency ablation (coblation): a promising new technique for laryngeal
      papillomata.
AB  - This paper describes a new application for radiofrequency ablation in head and
      neck surgery. Two patients with extensive laryngeal papillomata were successfully
      treated using this technology. The technique is described in detail, highlighting
      the main benefits of this approach as compared with existing techniques. These
      advantages include limited damage to underlying tissues and a bloodless field.

PMID- 17040602
TI  - Management of surgical airway emergencies by junior ENT staff: a telephone
      survey.
AB  - OBJECTIVE: To determine levels of confidence in the management of surgical airway
      emergencies by junior ENT staff. DESIGN: Telephone survey. PARTICIPANTS: 100
      Senior House Officers (SHOs) from 100 hospitals in the UK, providing 24 hour
      first on-call emergency ENT cover. METHOD: A list of questions was put to
      participants. The effects of different variables on confidence with airway
      emergencies and what SHOs considered to be adequate training were compared.
      RESULTS: Most SHOs provided cover for the management of surgical airway
      emergencies. Many of the participants were not confident to handle airway
      emergencies or felt that their training was inadequate. As expected, the amount
      of previous experience in ENT and the ability to perform advanced airway
      procedures gave SHOs greater confidence, but attendance at airway courses did
      not. CONCLUSION: Confidence in the management of airway problems is variable and
      does not correlate well with perceived adequacy of training. We suggest that
      systems of training in airway management are improved. Training issues may be
      better approached at an individual level, where deficiencies can be addressed.

PMID- 17040603
TI  - A comparison of the incidence of facial palsy following parotidectomy performed
      by ENT and non-ENT surgeons.
AB  - OBJECTIVE: To compare the complication rates of parotidectomy operations on
      benign histology performed by ENT and non-ENT surgeons. STUDY DESIGN AND SETTING:
      A seven-year (1994-2000) retrospective case notes review of patients undergoing
      parotidectomy in a United Kingdom district general hospital was performed.
      Patients with malignant histology were excluded. PARTICIPANTS: Patients were
      identified from the hospital computer database. One hundred and fifty-nine
      patients underwent parotidectomy for both benign and malignant conditions over
      the seven-year period. One hundred and thirty-seven (86 per cent) patients had
      parotidectomy for benign conditions and were included in this study. MAIN OUTCOME
      MEASURES: The presence or absence of facial palsy and other associated
      complications following parotidectomy surgery in both groups. RESULTS: The
      temporary facial palsy rates for ENT and non-ENT surgeons were 56 per cent and 57
      per cent, respectively. The permanent facial palsy rates for ENT and non-ENT
      surgeons were 2 per cent and 7 per cent, respectively. Differences in facial
      palsy were not statistically significant. The difference in other complication
      rates such as Frey's syndrome, haematoma, salivary fistula, and neuroma were also
      not statistically significant. CONCLUSION: Our complication rates were comparable
      with published results. There was no significant difference in the observed rate
      of post-operative facial nerve palsy and other known complications following
      parotid surgery performed by ENT and non-ENT surgeons.

PMID- 17040604
TI  - Methicillin resistant Staphylococcus aureus: is it a problem for nasal surgery?
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is becoming ever more
      prevalent in the UK, and the proportion of MRSA to methicillin sensitive
      Staphylococcus aureus (MSSA) seems to be increasing. New strains of MRSA are ever
      developing resistance to antibiotic treatment, increasing morbidity and mortality
      of infection. Staphylococcus aureus is part of the normal flora of the nose, and
      MRSA colonizes the nose in infection. However, nasal surgery is rarely
      complicated by staphylococcal infections, and MRSA infection following nasal
      surgery is rare. The authors present a literature review of MRSA infection, its
      relation to the nasal cavity, and infection following nasal surgery.

PMID- 17040605
TI  - A correlative study of NF-kappaB activity and cytokines expression in human
      chronic nasal sinusitis.
AB  - A growing body of literature suggests that cytokines play an important part in
      the pathogenesis of chronic nasal sinusitis. However, the mechanism by which the
      expression of cytokines in chronic nasal sinusitis is upregulated has not been
      well documented. The present study investigated the role of nuclear factor-kappa
      B (NF-kappaB) activation in upregulating the expression of interleukin-5, -6 and 
      8 (IL-5, IL-6 and IL-8). We titrated the levels of IL-5, IL-6 and IL-8 in nasal
      mucosa in 52 cases of chronic nasal sinusitis and 12 normal subjects using enzyme
      linked immunosorbent assay. According to whether allergic rhinitis was associated
      or not, we subdivided the patients into the AR group (with allergic rhinitis) and
      the NAR group (without allergic rhinitis). Semi-quantitative reverse
      transcription-polymerase chain reaction and immunohistochemical staining were
      used to evaluate expression and activation of NF-kappaB P50 and P65 subunits in
      nasal mucosa. The correlation between activities of P50 and P65 and cytokines
      expression was analysed. Our results showed that IL-5, IL-6 and IL-8 in both the
      AR and NAR groups were strikingly elevated in comparison with the control group
      (all p < 0.01 for AR group; p < 0.05, 0.05, 0.01, respectively, for NAR group);
      and they were even higher in the AR group than those in the NAR group (p < 0.01,
      0.05, 0.01, respectively). P50 and P65 mRNA levels in both AR and NAR groups were
      markedly greater than those in the control group (all p < 0.01); and the AR group
      had further higher levels as compared with the NAR group (both p < 0.05).
      Immunohistochemical study revealed that nucleus-positive rates of P50 and P65 in
      both AR and NAR groups were significantly higher than those of the control group
      (all p < 0.01), and they were much greater in the AR group in comparison with the
      NAR group (all p < 0.01). Pearson correlation analysis demonstrated that P50 and
      P65 nucleus-positive rates were closely correlated with IL-6 and IL-8 levels, but
      not IL-5, with a correlation coefficient of 0.49 for P50 and IL-6, 0.54 for P50
      and IL-8, 0.61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all p < 0.01). In
      conclusion, upregulated expression and activation of NF-kappaB P50 and P65 might
      be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic
      nasal sinusitis. Association of allergic rhinitis with chronic nasal sinusitis
      further enhanced NF-kappaB activity, and subsequently lead to even stronger
      expression of IL-6 and IL-8. IL-5 expression appeared to be independent of NF
      kappaB pathway in chronic nasal sinusitis.

PMID- 17040606
TI  - Actinomycetes colonization of tonsils: a comparative study between patients with
      and without recurrent tonsillitis.
AB  - OBJECTIVE: To determine the prevalence of tonsillar actinomycetes colonization in
      patients with and without recurrent tonsillitis and to study the association of
      this condition with recurrent tonsillitis and tonsillar hypertrophy. STUDY DESIGN
      AND SETTING: A retrospective study of 834 patients who had undergone
      tonsillectomy for recurrent tonsillitis (group A) and for sleep-disordered
      breathing without a history of recurrent tonsillitis (group B). RESULTS: The
      prevalence of tonsillar actinomycetes colonization was higher in patients who had
      undergone tonsillectomy for sleep-disordered breathing (44.1 per cent) than in
      patients who had undergone tonsillectomy for recurrent tonsillitis (33.3 per
      cent). The prevalence did not differ by sex or age of patient, although the
      occurrence rate was higher in the adult compared with the paediatric population.
      There was no statistically significant difference between the mean size of the
      tonsils removed in the two groups, and actinomycetes colonization did not affect
      tonsil size. Histopathological analysis of resected tonsils did not show active
      tissue infection. CONCLUSION: The presence of actinomyces does not indicate
      active disease. We are of the opinion that, although actinomyces colonization is
      more prevalent in patients with sleep-disordered breathing, it does not
      contribute to tonsillar hypertrophy nor to recurrent tonsillitis.

PMID- 17040607
TI  - Do all epistaxis patients with a nasal pack need admission? A retrospective study
      of 116 patients managed in accident and emergency according to a peer reviewed
      protocol.
AB  - INTRODUCTION: Epistaxis is the most common nasal emergency and if nasal packing
      is required this commonly results in admission. METHODS: A literature search
      could find no published (UK) protocols for the management of this common
      condition in accident and emergency (A&E) departments. This paper presents a
      retrospective review of 116 patients with epistaxis, following implementation of
      the new peer reviewed protocol in June 2004. RESULTS: Apart from cautery, 62 had
      nasal packing inserted. Only 17 required admission. Forty-six patients were
      discharged with nasal packing in situ and only seven (16 per cent) returned due
      to bleeding. The overall return rate was 11 per cent. DISCUSSION: We feel this is
      a safe and logical protocol. Compared to mandatory admission after nasal pack
      insertion, we saved 39 admissions in five months. There were also the added
      benefits to patients of being able to recuperate at home rather than in hospital
      and avoidance of the risk of hospital acquired infection.

PMID- 17040608
TI  - Is there objective evidence that septal surgery improves nasal airflow?
AB  - OBJECTIVE: To identify any prospective, controlled trials providing objective
      evidence of a reduction in nasal airway resistance following nasal septal
      surgery, and to undertake a meta-analysis of available data. METHODS: A
      systematic review with meta-analysis of data was undertaken. A systematic review
      of the literature using a defined search strategy was conducted to identify
      papers that used objective methods of airway assessment to evaluate the benefit
      of septal surgery. Accepted techniques for objective airway assessment included
      acoustic rhinometry, active anterior rhinomanometry and peak nasal inspiratory
      airflow. Papers were included based on pre-defined criteria, which included
      standardization of techniques as outlined in the guidelines of the 1984 committee
      report on the standardization of rhinomanometry. RESULTS: We identified 942
      articles, of which 13 were prospective studies evaluating the objective benefit
      of nasal septal surgery. Only three of these studies conformed to the inclusion
      criteria. A meta-analysis on these papers was performed using the Mantel-Haenszel
      method, and this demonstrated an overall reduction in nasal airway resistance
      following septal surgery for nasal obstruction (p=0.018). CONCLUSIONS: The
      majority of studies evaluating the objective benefit of septal surgery did not
      conform to the recommendations of the committee report on the standardization of
      rhinomanometry. Only three prospective controlled trials, with pooled data from
      141 cases, were identified for meta-analysis. The conclusions that can be drawn
      concerning objective improvement in airway function following nasal septal
      surgery are therefore limited. More long-term studies, adhering to standardized
      techniques, are needed to provide more convincing data.

PMID- 17040609
TI  - Electromyography of the cricoarytenoid unit during supracricoid laryngectomy with
      a cricohyoidoepiglottopexy procedure.
AB  - Two patients who received supracricoid laryngectomy with cricohyoidoepiglottopexy
      to treat laryngeal cancers, underwent intra-operative electromyography analysis.
      After the lesion was removed and the electrodes were inserted into the remaining
      intrinsic laryngeal muscles, the depth of anaesthesia was carefully reduced.
      Gentle tactile stimulations were applied to the pharynx to trigger the reflex
      movement of the remaining arytenoids. Recordings were made when reflex movement
      was achieved. Case one: Electromyography (EMG) of the remaining arytenoid
      demonstrated clear phase differences indicating reciprocal activities between the
      adductor group (lateral cricoarytenoid muscle, interarytenoid muscle) and the
      abductor muscle (posterior cricoarytenoid muscle). Case two: EMG of the remaining
      arytenoid demonstrated reciprocal activities between the interarytenoid muscle
      and the posterior cricoarytenoid muscle. Activity of the lateral cricoarytenoid
      muscle was not evident because the muscle was excised during removal of the
      paraglottic space. Mobility of the arytenoid was attributed to interaction
      between the interarytenoid muscle and posterior cricoarytenoid muscle. Reciprocal
      interaction between the interarytenoid muscle and posterior cricoarytenoid muscle
      alone is also capable of maintaining post-operative laryngeal functions after
      supracricoid laryngectomy with cricohyoidoepiglottopexy.

PMID- 17040610
TI  - Copying clinic letters to patients: a survey of patient attitudes.
AB  - Guidance from the Department of Health, published in 2000, stated that, 'as a
      matter of right', communications between clinicians would be copied to patients.
      In further guidance, the department indicated that, from April 2004, patients
      would receive copies of correspondence exchanged between healthcare
      professionals. There has been little research on this issue, and the few existing
      publications have come from the hospital psychiatric clinic setting. We examined
      the attitudes of 100 patients attending an ENT clinic as well as those of 100
      parents of children attending a paediatric ENT clinic in a general hospital out
      patient setting. At the end of consultations, patients or parents were invited to
      take part in the survey by completing a short questionnaire. Forty-three per cent
      of the adult patients and 44 per cent of the parents requested a copy of the
      clinic letter. These people were followed up by a telephone survey, three weeks
      after the copy of the clinic letter to the general practitioner was posted to the
      patient or parent. Eighty-one per cent of the patients and 77 per cent of the
      parents were successfully contacted for the follow-up telephone survey. Sixty per
      cent of the adults and 77 per cent of the parents reported that the copy of the
      clinic letter was helpful. There were no differences in responses between the
      adult patient and paediatric patient groups. In this study, less than half of
      both groups requested a copy of the ENT clinic letter to their general
      practitioner. To follow Department of Health guidance and copy the letter without
      patient consent is arguably contradictory to best practice and also to the
      concept of patient choice. There are significant financial implications in
      adopting the departmental guidance. We propose patients should be offered a copy
      of their clinic letter on request.

PMID- 17040611
TI  - Early pulmonary response in rats infected with Trichinella spiralis.
AB  - The migratory stage of Trichinella spiralis, the newborn larva, travels along the
      pulmonary microvascular system on its way to the striated muscle cells. In the
      present study, an important inflammatory reaction was observed on days 5 and 14
      post-infection (p.i.) in the lungs of infected rats. This inflammation was
      characterized by a Th2 cell phenotype of hyperplastic bronchus-associated
      lymphoid tissue and by goblet cell hyperplasia. Among the inflammatory cells were
      eosinophils and mast cells scattered over the pulmonary parenchyma. On day 5 p.i.
      the number of IgE(+), CD4(+) and CD5(+) cells in the bronchus-associated lymphoid
      tissue were increased and IgE-secreting lung cells were also detected. At the end
      of the migratory phase of the infection (day 14 p.i.), only IgE(+) cells were
      detected in high numbers and in the bronchoalveolar lavage fluid, an increment in
      the total IgE levels as well as the presence of IgE and IgA anti-larvae surface
      were also detected. In cytotoxicity assays, cells from the bronchoalveolar lavage
      had considerable biological activity since they were able to kill the larvae even
      in the absence of specific antibodies. These results show that the lung is an
      organ involved in the immune response developed early during a T. spiralis
      infection and suggest its importance in the protection of the host.

PMID- 17040612
TI  - Interactions between parasites of the cockle Austrovenus stutchburyi: hitch
      hikers, resident-cleaners, and habitat-facilitators.
AB  - The patterns of association between parasites within a particular host are
      determined by a number of factors. One of these factors is whether or not
      infection by one parasite influences the probability of acquiring other parasite
      species. This study investigates the pattern of association between various
      parasites of the New Zealand cockle Austrovenus stutchburyi. Hundreds of cockles
      were collected from one locality within Otago Harbour, New Zealand and examined
      for trematode metacercariae and other symbionts. Two interspecific associations
      emerged from the study. First, the presence of the myicolid copepod Pseudomyicola
      spinosus was positively associated with higher infection intensity by
      echinostomes. The side-effect of the copepod's activities within the cockle is
      suggested as the proximate mechanism that facilitates infection by echinostome
      cercariae, leading to a greater rate of accumulation of metacercariae in cockles
      harbouring the copepod. Second, a positive association was also found between
      infection intensity of the metacercariae of foot-encysting echinostomes and that
      of gymnophallid metacercariae. This supports earlier findings and suggests that
      the gymnophallid is a hitch-hiker parasite because, in addition to the pattern of
      positive association, it (a) shares the same transmission route as the
      echinostomes, and (b) unlike the echinostomes, it is not capable of increasing
      the host's susceptibility to avian predation. Thus, both active hitch-hiking and
      incidental facilitation lead to non-random infection patterns in this parasite
      community.

PMID- 17040614
TI  - Cochlear implantation in the irradiated temporal bone.
AB  - OBJECTIVE: To demonstrate the feasibility and complexities of cochlear
      implantation in the setting of bilateral temporal bone osteoradionecrosis. STUDY
      DESIGN: Case report. SETTING: Tertiary care referral centre. CASE DESCRIPTION: A
      66-year-old woman with bilateral temporal bone osteoradionecrosis and profound
      hearing loss, following treatment for tonsillar cancer, underwent cochlear
      implantation. Prior canal wall down mastoidectomy and subsequent temporal bone
      resection with free flap reconstruction had been performed on the implanted ear.
      The contralateral ear received a canal wall down mastoidectomy. A completely
      dehiscent mastoid segment of the facial nerve and extensive fibrosis were evident
      in the implanted ear. Only minimal fibrous reaction was found within the cochlea,
      allowing for full electrode insertion. At three months, speech recognition
      testing documented a consonant-nucleus-consonant (CNC) word score of 54 per cent.
      CONCLUSIONS: This report demonstrates the feasibility of cochlear implantation
      after temporal bone surgery and free flap reconstruction in the setting of
      diffuse osteoradionecrosis. The patient's excellent open-set speech understanding
      using the cochlear implant implies that radiation did not severely damage the
      central auditory pathways. Thus, some patients with radiation-induced hearing
      loss may be appropriate cochlear implant candidates. Special attention should be
      paid to surgical planning, as complications related to wound healing, electrode
      insertion and facial nerve injury may be more likely.

PMID- 17040615
TI  - Application of ligating loops to control bleeding during endoscopic surgery for a
      highly vascular hypopharyngeal tumour.
AB  - Endoscopic treatment of hypervascular lesions of the hypopharynx is challenging
      because of difficulty in controlling bleeding during surgery. We report a highly
      vascular hypopharyngeal solitary fibrous tumour treated by endoscopic laser
      surgery combined with ligating loops. Application of dual ligating loops provided
      easy and secure haemostasis of the feeding artery before resection. Since the
      endoscopic approach is less invasive than the external approach, we confirm that
      it is worthwhile to attempt an endoscopic approach using ligating loops before
      resorting to the external approach in the treatment of hypervascular
      hypopharyngeal lesions.

PMID- 17040613
TI  - Determination of thermodynamics and kinetics of RNA reactions by force.
AB  - Single-molecule methods have made it possible to apply force to an individual RNA
      molecule. Two beads are attached to the RNA; one is on a micropipette, the other
      is in a laser trap. The force on the RNA and the distance between the beads are
      measured. Force can change the equilibrium and the rate of any reaction in which
      the product has a different extension from the reactant. This review describes
      use of laser tweezers to measure thermodynamics and kinetics of
      unfolding/refolding RNA. For a reversible reaction the work directly provides the
      free energy; for irreversible reactions the free energy is obtained from the
      distribution of work values. The rate constants for the folding and unfolding
      reactions can be measured by several methods. The effect of pulling rate on the
      distribution of force-unfolding values leads to rate constants for unfolding.
      Hopping of the RNA between folded and unfolded states at constant force provides
      both unfolding and folding rates. Force-jumps and force-drops, similar to the
      temperature jump method, provide direct measurement of reaction rates over a wide
      range of forces. The advantages of applying force and using single-molecule
      methods are discussed. These methods, for example, allow reactions to be studied
      in non-denaturing solvents at physiological temperatures; they also simplify
      analysis of kinetic mechanisms because only one intermediate at a time is
      present. Unfolding of RNA in biological cells by helicases, or ribosomes, has
      similarities to unfolding by force.

PMID- 17040616
TI  - Parental satisfaction with health services provided to children with Down
      syndrome in north-west England: an ENT perspective.
AB  - AIMS: To evaluate parents' satisfaction with medical and allied health services
      provided to children with Down syndrome in north-west England, comparing ENT and
      its allied services with other areas of health service provision. METHODS: A
      questionnaire survey of parents attending a north-west England Down syndrome
      association conference. Demographic data, departments visited, satisfaction with
      each service (scored one to five), waiting times for each service (scored one to
      five), service need (scored one to three) and accessibility (scored one to three)
      were recorded. RESULTS: Otolaryngology had been used by 50 per cent of children,
      with a satisfaction of 2.63 (the second worst score). Speech and language therapy
      was used by 90 per cent of the children, with a satisfaction of 3.26 (the worst
      score). The service felt to be most needed and also most difficult to access was
      speech and language therapy. CONCLUSION: Otorhinolaryngology departments should
      assess how they can improve their service to this population with specific ENT
      needs. Speech and language services for children with Down syndrome should be
      expanded.

PMID- 17040618
TI  - Induction therapy for adults with acute lymphoblastic leukemia.

PMID- 17040617
TI  - Evaluation of the clinical utility of diagnostic versus therapeutic interventions
      in oncology: related but quite different processes.

PMID- 17040619
TI  - Improving outcomes in difficult bone cancers using multimodality therapy,
      including radiation: physician and nursing perspectives.
AB  - Principles of therapy are similar for Ewing's sarcoma and osteosarcoma.
      Chemotherapy or surgery alone cures few patients. Multimodality measures are
      needed for durable response. Quality of life and function are very important
      short- and long-term considerations. The spine, sacrum, pelvis, ankle, hand,
      mediastinum, pulmonary hilum, and chest wall are examples of bone cancer
      locations for which surgery is difficult. Patients with positive margins may need
      radiation and may experience systemic therapy delay, recurrence, loss of
      function, or any combination of these. When radiation is used as a means of local
      control, concomitant chemotherapy can increase its effectiveness. Options for
      difficult Ewing's sarcoma and osteosarcoma situations and multimodality
      solutions, including 1 mCi/kg of samarium and proton therapy, are discussed.
      Combination radiation and chemotherapy regimens are summarized, and organization
      of patients, caregivers, and medical teams for multimodality therapy is
      described, along with tools used in our institution that aid in this process.

PMID- 17040620
TI  - Molecular genetics of pediatric central nervous system tumors.
AB  - Recent advances in molecular biology have enhanced our understanding of the
      pathogenesis of brain tumors, particularly in children. The use of molecular
      diagnostic tools is quickly becoming a standard component in the diagnosis and
      classification of brain tumors in children, in addition to providing insight
      leading to treatment stratification and improved outcome prediction. All new
      protocols involving treatments for brain tumors in children include studies of
      biomarkers and biologic correlates as a means to identify new targets for
      therapeutics and possible intervention strategies.

PMID- 17040621
TI  - Induction of apoptosis in lymphoid and myeloid leukemia.
AB  - Defects in the core machinery of the apoptosis pathway contribute to
      chemoresistance and poor outcomes in patients with acute leukemia. To overcome
      these defects, novel molecules that target key proteins in the apoptosis pathway
      are being developed. This review highlights compounds that target the
      mitochondrial, death receptor, and convergence pathways of caspase activation
      that are being developed for the treatment of acute leukemia.

PMID- 17040622
TI  - Gene therapy for ovarian cancer.
AB  - Ovarian cancer remains the leading cause of death due to gynecologic cancer in
      women in the United States. Gene and viral-based therapies represent novel
      therapeutic approaches for cancer. The manipulation of genetic content of tumor
      cells toward a therapeutic end has been divided into several general strategies,
      including molecular chemotherapy, mutation compensation, immunopotentiation, and
      virotherapy. Improvements in delivery vehicles and in evaluation of gene transfer
      and viral replication remain important areas of investigation. We highlight the
      most recent advances in these novel therapeutic approaches for ovarian cancer and
      include a summary of recent clinical trials.

PMID- 17040623
TI  - The current treatment of recurrent ovarian cancer.
AB  - Contemporary management of recurrent ovarian, primary peritoneal, and fallopian
      tube cancers has continued to evolve and now offers women the hope of extended
      survival with an improved quality of life. Platinum continues to be the single
      most active agent in the treatment of ovarian cancer, but acquired resistance to
      platinum often emerges. Fortunately, a number of novel agents and treatment
      strategies have been developed to meet the goals of ameliorating symptoms while
      extending survival. Classically, patients have been treated based upon the
      interval from last platinum administration during front-line therapy until time
      of recurrence. This review focuses upon the current treatment strategies used for
      platinum-refractory, platinum-resistant, and platinum-sensitive patients. The
      incorporation of targeted biologic agents is also discussed, along with the role
      of secondary cytoreduction. It is hoped that the results of future and ongoing
      clinical trials will offer further advances in the treatment of this devastating
      disease.

PMID- 17040624
TI  - Historical progress in the initial management of ovarian cancer: intraperitoneal
      chemotherapy.
AB  - Despite measured improvement in survival with the introduction of the platinates
      and taxanes in treatment of advanced ovarian cancer, little additional progress
      has been made with conventional cytotoxic agents. Recently, the Gynecologic
      Oncology Group (GOG) published data from a study evaluating the merits of
      intraperitoneal chemotherapy in women with advanced, optimally cytoreduced
      ovarian cancer. They documented a significant advantage in progression-free and
      overall survival for the experimental regimen, a combination of intravenous
      paclitaxel and intraperitoneal cisplatin and paclitaxel, compared with standard
      intravenous cisplatin and paclitaxel chemotherapy. The intraperitoneal regimen
      was substantially more toxic and was associated with reduced short-term quality
      of life. The GOG trial joins six other published phase III trials since 1994
      comparing intravenous with intraperitoneal chemotherapy in advanced-stage
      epithelial ovarian cancer. A recent meta-analysis suggests a 21% reduction in the
      hazard for progression (four studies) and death (seven studies). Reluctance to
      adopt a new standard of care is rooted in toxicity concerns. Further evaluation
      is warranted to clarify unanswered questions regarding administration schedule,
      agents, techniques, number of courses, and patient eligibility for
      intraperitoneal chemotherapy.

PMID- 17040625
TI  - Current and emerging treatment approaches for tobacco dependence.
AB  - Nicotine in tobacco is the primary reason why most people find it hard to stop
      using tobacco. Nicotine creates dependence by activating the dopaminergic reward
      system in the brain. Physiologic withdrawal symptoms that occur when nicotine is
      no longer administered reinforce continued nicotine administration to avoid
      withdrawal. Extrapolating from this evidence has led to the development of
      tobacco dependence pharmacotherapy based upon the concept of replacing and/or
      blocking the effects of nicotine in the brain. The efficacy of nicotine
      replacement and blockade treatments in lessening symptoms of nicotine withdrawal
      and increasing quit rates has been consistently demonstrated in clinical trials.
      Despite the availability of efficacious medications to treat nicotine dependence,
      current therapies remain underutilized across the population. Health-care
      providers need to systematically encourage all tobacco users to quit and ensure
      that their tobacco-using patients use evidence-based treatments when they attempt
      to quit.

PMID- 17040627
TI  - Screening tests for colorectal cancer: a menu of options remains relevant.
AB  - Until the early 1990s, no evidence was available to show that screening for
      colorectal cancer (CRC) by any means actually saved lives. Subsequently,
      sufficient evidence for the efficacy of fecal occult blood testing (FOBT) and
      flexible sigmoidoscopy allowed the US Preventive Services Task Force to publish
      guidelines for CRC screening. Since that time the major organizations in the
      United States concerned with screening guidelines have recommended a menu of
      screening test options including FOBT, flexible sigmoidoscopy, flexible
      sigmoidoscopy plus FOBT, barium enema, and colonoscopy. No organization, except
      for the American College of Gastroenterology, has designated any one of these
      options as "preferred." Nevertheless, the lay press and many gastroenterology
      opinion leaders have encouraged Americans to have only one test--colonoscopy. In
      this review we discuss the rationale for caution in designating one screening
      test as "the best" and present information on how new stool and serum tests can
      be used effectively to screen for CRC.

PMID- 17040628
TI  - [Spanish version of the DASH questionnaire. Cross-cultural adaptation,
      reliability, validity and responsiveness].
AB  - BACKGROUND AND OBJECTIVE: The Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire is a specific outcome instrument developed to measure upper
      extremity disability and symptoms. The aim of this work is to develop a Spanish
      version of the DASH questionnaire and to analyze its reliability, validity and
      responsiveness. MATERIAL AND METHOD: We performed cross-cultural adaptation of
      the DASH to Spanish, using a process that included double forward and backward
      translations, expert review and field-testing. The Spanish version's reliability,
      content, construct and criterion validity and responsiveness were then evaluated
      in 98 patients with upper-extremity conditions that completed the DASH and SF-36
      generic health questionnaire before and after medical rehabilitation treatment.
      RESULTS: We obtained a Spanish DASH version (DASHe) linguistically and
      conceptually equivalent to the original version. Internal consistency of the
      DASHe was high (Cronbach alpha = 0.96), test-retest reliability was excellent (r
      = 0.96) and the floor and ceiling effects were negligible. Construct and criteria
      validity was shown by a positive association of DASHe scores with worse
      condition, and a significant correlation with the SF-36 scores, stronger with the
      SF-36 pain dimension. Responsiveness was excellent (effect size and standardized
      response means higher than 0.80). CONCLUSIONS: The DASHe is a reliable, valid and
      responsive instrument that can provide a standardized measure in Spanish patients
      with upper-extremity musculoskeletal conditions.

PMID- 17040626
TI  - Molecular screening for breast cancer prevention, early detection, and treatment
      planning: combining biomarkers from DNA, RNA, and protein.
AB  - The completion of the human genome project, along with the ancillary technologies
      derived from this effort, provides the ability to comprehensively analyze patient
      tumors as well as the individual patient's own genetic make-up at the DNA, RNA,
      and protein level. As a result, novel molecular screening techniques have the
      potential to push the boundaries of detection to even smaller tumors and also to
      allow accurate risk assessment, cancer prevention, and treatment planning in
      individual women. This review focuses on advances over the past 2 years in the
      use of molecular signatures and circulating tumor cells for early breast cancer
      detection and for prediction of response to therapy.

PMID- 17040629
TI  - [Infectious diarrhea study in Castellon, Spain (EDICS): population incidence of
      sporadic cases in 2004 and comparison with the year 2000].
AB  - BACKGROUND AND OBJECTIVE: Infectious intestinal diseases are highly prevalent,
      and among them sporadic cases are the most common processes. The aim of this
      study was to estimate the incidence of sporadic cases diagnosed in a healthcare
      district of Castellon (Spain) in the year 2004, and to compare them with those of
      the year 2000. MATERIAL AND METHOD: Based on routine coprocultures and individual
      demographic data of each patient, we calculated the population rates by age for
      the more frequent microorganisms, especially detailed for children up to 5 years
      of age. We report the results of the year 2004, and compare these with the
      previous study of the year 2000. RESULTS: Campylobacter showed the highest rate
      (1.01 x 103), followed by Salmonella (0.75), each without significant differences
      regarding the year 2000. The rate of rotavirus cases (0.65) was smaller than in
      2000; and for adenovirus 2004 was an atypical seasonal year. In children younger
      than 3 years, rates were 26.54; 10.23 and 11.75. As in the previous study, the
      age-distribution in children < 5 years was very particular. An U inverted shape
      was seen for Campylobacer, and the rates for rotavirus decreased after the peak
      observed in the youngest group (< 6 months). Among hospitalized patients
      rotavirus was the most common and Campylobacter the less common. CONCLUSIONS: The
      epidemiological traits of the rates by age until the age of five are
      characteristic for each microorganism, as are the proportions of hospitalization.
      Rates of Campylobacter and Salmonella in the year 2004 were similar to the year
      2000, but a decrease in the rotavirus rates was observed.

PMID- 17040630
TI  - [Swelling of the bronchial mucose and quickness of onset in acute asthma].
AB  - BACKGROUND AND OBJECTIVE: The plasma protein leakage produced in the bronchial
      mucose of patients with acute asthma might be associated to the quickness of the
      onset exacerbation. The aim of this study was to study this association. PATIENTS
      AND METHOD: 22 patients with acute asthma were recruited, and the magnitude of
      plasma protein leakage was measured by the concentrations of albumin and alpha2
      macroglobulin in sputum. RESULTS: Days of onset in acute asthma correlated
      negatively with albumin sputum concentration (r = -0.563; p = 0.006), alpha2
      macroglobulin sputum concentration (r = -0.603; p = 0.003), and related relative
      coefficients of albumin sputum/serum (r = -0.538; p = 0.01) and alpha2
      macroglobulin sputum/serum (r = -0.514; p = 0.014). When the sample was divided
      by the following daily cutoff: < or = 4, patients suffering from a shorter onset
      of acute asthma showed a higher concentration of alpha2-macroglobulin in sputum:
      mean (standard deviation) of 14.4 (18) versus 5.3 (5.4) (p = 0.028). CONCLUSIONS:
      Plasma protein leakage seems to play an important role in the inflammatory
      pathogenesis of asthma exacerbation. The quicker onset of asthma the more plasma
      protein extravasation to the bronchial lumen.

PMID- 17040631
TI  - [Upper extremity related disorders and quality of life].

PMID- 17040632
TI  - [Open access and the Spanish medical journals].

PMID- 17040633
TI  - [Pathogenesis of lipodystrophy and metabolic syndromes associated with HIV
      infection].
AB  - Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance)
      associated with human immunodeficiency virus (HIV) infection, is a multifactorial
      syndrome due to the interaction of host related factors (cellular immune status,
      diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty
      acid or PUFA depletion), and pharmacological effects (mitochondrial DNA
      polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction).
      HIV probably modifies the adipocyte differentiation and the lipid metabolism.
      This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis
      factor) and the participation of other factors (drugs, diet), all in the context
      of a particular host genetic setting. The adipocyte (and several cellular
      receptors, fatty acids, membrane proteins, and cytokines) plays a central role in
      the pathogenesis of HIV-associated lipodystrophy.

PMID- 17040634
TI  - [Lack of compliance of recommendations of endocarditis prophylaxis in
      outpatients].

PMID- 17040635
TI  - [Prevalence of positive prick-test to latex in the surgical population].

PMID- 17040636
TI  - [Agenesia of inferior vena cava in young adults with iliac deep vein thrombosis].

PMID- 17040637
TI  - [Epiploic appendagitis: an entity to be considered in the differential diagnosis
      of patient with clinical suspicious of appendicitis or diverticulitis].

PMID- 17040638
TI  - [Pituitary apoplexy following treatment for acute coronary syndrome].

PMID- 17040639
TI  - [Good response to treatment with rituximab in a child with refractory idiopathic
      thrombocytopenic purpura].

PMID- 17040640
TI  - [Isolated IIIrd nerve palsy as the only sign of chronic subdural haematoma].

PMID- 17040641
TI  - [Exposure to risk factors across the life course and cardiovascular disease].

PMID- 17040642
TI  - [Prioritizing patients on waiting list for cataract surgery: preference
      differences among citizens].
AB  - OBJECTIVES: To estimate and compare citizen preferences regarding patient
      prioritization for cataract surgery. METHOD: A conjoint analysis was performed.
      Priority criteria were identified and selected using 4 focus/nominal groups
      consisting of the general public, patients/relatives, allied health-professionals
      and specialists from Catalonia (n=36). Preferences elicitation (score of
      criteria): representative sample survey of the above mentioned groups (n=771) and
      rank-ordered logit model application. Differences were assessed by group analysis
      and their comparison. RESULTS: The criteria selected and their relative
      importance were: visual impairment (45%), difficulty in performing activities of
      daily living (ADL) (15%), limitation of ability to work (14%), being looked after
      by someone (11%), being a caregiver (8%), and recovery probability (7%).
      Differences in scores were observed among groups. Visual impairment was scored
      more highly by the general public and patients/relatives than by other groups
      (p<0.001). These two groups also assigned less importance to difficulty in
      performing ADL (p<0.001). The probability of recovery was the least scored
      criterion by most groups. Correlations among the order of hypothetical patient
      scenarios were high (r>0.9). However, the final order of patients on the waiting
      list could differ by up to 27 positions when different group scores were applied.
      CONCLUSIONS: Social and clinical criteria were considered important. The observed
      differences among citizens regarding how to prioritize patients on the waiting
      lists indicates the need to take into account the preferences of all groups of
      citizens.

PMID- 17040643
TI  - [Association of income with use of and access to health services in Spain at the
      beginning of the XXI century].
AB  - OBJECTIVE: To estimate the association of household income and provincial income
      with visits to general practitioners and specialists and with hospitalization and
      to determine whether waiting times to access these services vary with both
      economic variables. METHOD: Data from the 2001 National Health Survey were used.
      The association was estimated by sex- and age-adjusted odds ratios; in the case
      of per capita income, odds ratios were also adjusted for household income.
      Percentiles and the geometric mean of waiting times in each health service were
      estimated and the statistical significance of their association with both
      economic variables was evaluated. RESULTS: Subjects with the lowest household
      income showed the highest frequency of visits to general practitioners and
      hospitalization, although they waited longer for hospital admission. Subjects
      with the lowest household income also showed the lowest frequency of specialist
      visits: the odds ratio in the lowest income quartile with respect to the highest
      income quartile was 0.73 (95% CI: 0.62-0.87). However, when only visits to
      specialists working in the public system were analyzed, the lowest frequency of
      visits was observed in subjects with the highest household income. No differences
      were found in health services utilization or in waiting times according to
      provincial income. CONCLUSIONS: The frequency of specialist visits according to
      household income shows a different pattern from that observed for visits to
      general practitioners and hospitalizations. The longest waiting times for
      admission to hospital were observed in subjects with the lowest household income.

PMID- 17040644
TI  - [Famine in the Spanish civil war and mortality from coronary heart disease: a
      perspective from Barker's hypothesis].
AB  - OBJECTIVE: To determine whether the famine experienced during the Spanish civil
      war and immediate postwar period influenced mortality from coronary heart disease
      (CHD) in persons born in this period, following the lines of Barker's hypothesis
      on fetal programming of chronic diseases in adult life. METHODS: Using CHD
      mortality data by age and sex for 1990-2002, annual and age-adjusted rates were
      calculated by the direct method. Poisson regressions were used to estimate
      period, age and cohort effects by year of birth (1918-1957). RESULTS: During the
      study period, CHD mortality fell by a yearly average of -2.3% in both sexes and
      in all ages yearly. This trend was influenced by both cohort and period effects
      (p<0.001); an increased risk was observed for both sexes and in all ages in the
      deaths corresponding to persons born during the war and postwar years when the
      famine was most intense (1937, 1940, 1943 and 1945). CONCLUSIONS: The results
      obtained by studying yearly CHD mortality are compatible with those expected by
      Barker's hypothesis of the effect of nutritional stress during pregnancy. In
      addition to its human, economic and political costs, the Spanish civil war could
      also have had negative consequences for the health of persons born in this
      period.

PMID- 17040645
TI  - Evaluation of the research methodology in genetic, molecular and proteomic tests.
AB  - INTRODUCTION: The advances in genomic analysis technologies have conducted to the
      development of new diagnostic tests in the clinical practice. As well as it
      happened in other diagnostic fields, the knowledge of the main flaws affecting
      genetic investigation will facilitate the application of the results. METHODS: We
      included 44 original articles that evaluate diagnostic exactitude of genetic and
      molecular tests (including proteomic), published from 2002 to June 2005 in five
      international publications: JAMA, Lancet, New England Journal of Medicine, Cancer
      Research and Clinical Cancer Research. We examined adherence to 24 methodological
      criteria included in the guide STARD (Standards for Reporting of Diagnostic
      Accuracy. RESULTS: The mean number of methodological criteria satisfied was 9.8
      (95% CI 8.8-10.6); the greater deficiencies were in aspects related to the
      description of patient's selection 9 (20%), the treatment of indeterminate
      results 5 (11%) and the determination of test reproducibility 6 (13%). It was
      observed a high fulfillment in the description of the gold standard 39 (87%) and
      in the methodology of the test 28 (62%). DISCUSSION: The methodologic quality of
      the evaluated articles is lower than the quality observed in other research
      fields. The methodologic aspects that most need improvement are those linked to
      the clinical information of the populations studied and the reproducibility of
      the tests. The research and development of new genetic-molecular technologies
      requires a better fulfillment of the epidemiological and clinical criteria
      already followed by other diagnostic fields.

PMID- 17040646
TI  - [Safety-engineered devices to prevent percutaneous injuries: cost-effectiveness
      analysis on prevention of high-risk exposure].
AB  - OBJECTIVE: To assess the efficiency of the replacement of several medical devices
      by engineered sharp injury (SI) prevention devices (ESIPDs). METHODS: The cost
      effectiveness ratios of the replacement of medical devices in use by ESIPDs were
      estimated: their purchasing costs and the direct costs of sharp injury care were
      taken into account; the number of SI avoidable by each ESIPD was estimated from
      the 252 occupational SI notified by healthcare workers at a 1,300 bed hospital
      from March 2002 to February 2003. The relationship between ESIPD additional costs
      and the number of high-risk SI was estimated (SI were classified as high-risk if
      they met two or more of the following criteria: moderately-deep or deep injury,
      injury with a device previously inserted in an artery or vein, or with a device
      exposed to blood). RESULTS: ESIPDs order according to cost-effectiveness ratio:
      safety needle for implanted ports (-2.65 euro/SI avoided), followed by syringes
      with protective shield (869.79 euro/SI), resheathable winged steel needles,
      needleless administration sets, and short catheters with protective encasement.
      ESIPDs order according to relationship between additional costs and number of
      high-risk sharp injuries avoided: safety needles for implanted ports, followed by
      winged steel needles, hypodermic syringes, short catheter and needleless
      administration sets. CONCLUSIONS: Savings in SI care outweigh additional costs of
      certain ESIPDs. Cost-effectiveness analysis is useful in assigning priorities;
      however the risks of SI by every device must be taken into account.

PMID- 17040647
TI  - [Cost of assisted reproduction technology in a public hospital].
AB  - OBJECTIVES: Most studies on the costs of assisted reproductive technologies (ART)
      identify the total cost of the procedure with the direct cost, without
      considering important items such as overhead or intermediate costs. The objective
      of this study was to determine the cost per ART procedure in a public hospital in
      2003 and to compare the results with those in the same hospital in 1998. METHODS:
      Data from the Human Reproduction Unit of the Virgen de las Nieves University
      Hospital in Granada (Spain) from 1998 and 2003 were analyzed. Since the total
      costs of the unit were known, the cost of the distinct ART procedures performed
      in the hospital was calculated by means of a methodology for cost distribution.
      RESULTS: Between 1998 and 2003, the activity and costs of the Human Reproduction
      Unit analyzed evolved differently. Analysis of activity showed that some
      techniques, such as intracytoplasmic sperm injection, were consolidated while
      others, such as stimulation without assisted reproduction or intracervical
      insemination were abandoned. In all procedures, unit costs per cycle and per
      delivery decreased in the period analyzed. CONCLUSIONS: Important changes took
      place in the structure of costs of ART in the Human Reproduction Unit of the
      Virgen de las Nieves University Hospital between 1998 and 2003. Some techniques
      were discontinued, while others gained importance. Technological advances and
      structural innovations, together with a "learning effect," modified the structure
      of ART-related costs.

PMID- 17040648
TI  - [Comment. On studies of the costs of healthcare processes].

PMID- 17040649
TI  - [Smoking cessation in Galician [Spain] smokers during pregnancy and breast
      feeding, 1954-2004].
AB  - OBJECTIVE: To determine how many women living in Galicia (Spain) quit smoking
      during pregnancy and in the first 6 months of breast feeding. A second objective
      was to identify possible temporal changes in smoking cessation. METHOD: Data
      retrospectively provided by smokers and ex-smokers living in Galicia were
      analyzed. RESULTS: A total of 31.9% (26.9-37.0) of Galician smokers did not quit
      smoking during pregnancy or in the 6 first months of breast feeding. No
      statistically significant differences were found in the percentage of women who
      stopped smoking in relation to the period when they became pregnant. A tendency
      towards lower cessation rates was found. CONCLUSIONS: A high percentage of
      pregnant women do not quit smoking during pregnancy or in the first 6 months of
      breast feeding. These data indicate that health policies on smoking during
      pregnancy and breast feeding should be improved.

PMID- 17040650
TI  - [Evolution of health inequalities in Catalonia [Spain]].
AB  - OBJECTIVE: To analyze the evolution of social inequalities in health in Catalonia
      (Spain) in the last 20 years. METHODS: Mortality in 354 small areas of Catalonia
      (288 cities in Catalonia and 66 health areas in the city of Barcelona) was
      analyzed for the 1984-98 period. Indicators of self-perceived health status,
      lifestyles, and health services utilization by social class and gender were
      compared for 1994 and 2002. Factors related to occupational health, immigration
      and health, environmental health, and policies to reduce social inequalities in
      health were also analyzed. RESULTS: Although most health indicators improved,
      multiple inequalities in health were found in both 1994 and 2002. These
      inequalities were the same in 2002 as in 1994 or, in some cases, worse. The
      collectives with the worst indicators were persons living in the most deprived
      areas, those from disadvantaged social classes, women, and immigrants from low
      income countries. CONCLUSION: Social inequalities in health have persisted over
      the past 20 years in Catalonia. We present some recommendations on health
      information systems, research, and policies to reduce these inequalities.

PMID- 17040651
TI  - [Drunk driving in professional drivers in the Via Blanca highway in Cuba].
AB  - To determine the frequency of drunk driving in professional drivers (Via Blanca,
      Havana City), we carried out a descriptive study of 832 drivers selected by
      multistage stratified sampling. A structured interview with each driver was
      carried out to record the variables under study, and a breath alcohol test was
      subsequently performed. The frequency of drunk driving was 8.18% (95% CI, 5.94%
      10.42%), with a predominance of drivers with alcohol levels<or=0.24% (51.07%).
      Drunk driving was more frequent in "high risk" hours, in drivers aged between 40
      and 49 years old (10.3%), and in those with 15 to 24 years of experience
      (11.02%). The frequency of drunk driving found in this study highlights the need
      to design traffic accident prevention strategies.

PMID- 17040652
TI  - [Myths and fears: precautions against avian influenza are justified by the
      mechanism of transmission].

PMID- 17040653
TI  - [Epidemiology: discipline or method].

PMID- 17040654
TI  - [Quality, quality and quality].

PMID- 17040655
TI  - [Chronic obstructive pulmonary disease in life and death].

PMID- 17040656
TI  - [Evolution of patients with chronic obstructive pulmonary disease, obesity
      hypoventilation syndrome or congestive heart failure in a respiratory monitoring
      unit].
AB  - OBJECTIVE: We compared the use of noninvasive ventilation (NIV) for hypercapnic
      acidosis with hypoxemia in patients with chronic obstructive pulmonary disease
      (COPD), obesity hypoventilation syndrome (OHS), or congestive heart failure (CHF)
      in a respiratory medicine monitoring unit. The objective was to evaluate each
      diagnostic groups response to therapy in terms of clinical course and evolution
      of blood gases. PATIENTS AND METHODS: Prospective, 12-month study of 53 patients
      with hypercapnic acidosis with hypoxemia. Twenty-seven patients had COPD, 17 OHS,
      and 9 CHF. Severity was assessed based on initial arterial blood gas analysis.
      Clinical course was studied by blood gas analysis after conventional treatment
      and after NIV (1-3 hours and 12-24 hours). Mortality was recorded. All patients
      received bilevel positive airway pressure support in assist-control mode.
      RESULTS: No significant differences were observed between mean (SD) initial pH
      findings in the 3 diagnostic groups: COPD, 7.28 (0.1); OHS, 7.29 (0.09); and CHF,
      7.24 (0.07). (nonsignificant differences). After initial conventional treatment,
      PaCO2 worsened for COPD patients (P = .026) and PaO2 improved for CHF patients (P
      = .028). After 1 to 3 hours of NIV, pH (P = .002) and PaO2 (P = .041) improved
      for COPD patients, and pH (P = .03) and PaCO2 (P = .045) improved in OHS
      patients; no significant changes were observed in CHF patients. After 12 to 24
      hours of NIV, the mean pH was 7.36 (0.04) for COPD patients, 7.36 (0.05) for OHS
      patients, and 7.25 (0.1) for CHF patients (not significant). The mortality rate
      was 11.1% for COPD, 0% for OHS, and 33.3% for CHS (not significant, P = .076).
      CONCLUSIONS: In this group of patients with similar initial arterial blood gas
      values, response to NIV was seen to be better in OHS and COPD than in CHF. That
      the start of NIV is usually preceded by a poor response to conventional COPD
      treatment suggests that delaying NIV should be reconsidered.

PMID- 17040657
TI  - [Treatment and course of community-acquired pneumonia caused by atypical
      pathogens].
AB  - OBJECTIVE: To study the course of disease and outcomes in a group of patients
      with community-acquired pneumonia caused by atypical pathogens (Mycoplasma
      pneumoniae, Legionella species ,Coxiella burnetii, and Chlamydophila pneumoniae)
      according to the empiric treatment received. PATIENTS AND METHODS: Of a total of
      390 patients admitted to our hospital with pneumonia between January 1996 and
      February 2001, the causative microorganism was an atypical pathogen in 89 cases.
      Patients were divided retrospectively into 2 groups according to the empiric
      treatment they received: group A, who had received an antibiotic regime
      (quinolones or macrolides) that provided coverage for atypical pathogens; and
      group B, who had received treatment that did not provide such coverage. Clinical
      course was assessed in terms of the differences between the 2 groups in length of
      hospital stay, radiographic resolution, readmission at 30 days after discharge,
      and mortality. RESULTS: A total of 89 patients with pneumonia caused by atypical
      pathogens (39 in group A and 50 in group B) were studied. No significant between
      group differences in the variables were found. CONCLUSIONS: In this group of
      patients hospitalized for community-acquired pneumonia, antibiotic regimens
      providing coverage for atypical pathogens did not improve either clinical or
      radiographic evolution.

PMID- 17040658
TI  - [Functional status and survival in patients with chronic obstructive pulmonary
      disease following pulmonary rehabilitation].
AB  - OBJECTIVES: To study functional status and survival in patients with chronic
      obstructive pulmonary disease (COPD) following a pulmonary rehabilitation
      program. PATIENTS AND METHODS: We assessed lung function, 6-minute walk distance,
      Borg score for dyspnea upon completion of the 6-minute walk, workload in watts on
      a cycle ergometer, quality of life using the St George's Respiratory
      Questionnaire (SGRQ); the body-mass index, airflow obstruction, dyspnea, and
      exercise capacity (BODE) index; and survival. RESULTS: One hundred five patients
      participated in the pulmonary rehabilitation program. The patients had a mean
      (SD) age of 63.9 (9.3) years, body mass index of 24.5 (4.56) kg/m2, and forced
      expiratory volume in 1 second (FEV1) of 0.91 (0.46) L. The mean distances walked
      in 6 minutes were 412.8 (79.4) m before the pulmonary rehabilitation program and
      443.46 (81.57) m after rehabilitation. The mean workloads on the cycle ergometer
      before and after rehabilitation, respectively, were 47.9 (29.6) W and 77.76
      (20.88) W. The mean Borg scores were 2.2 (1.37) before and 1.47 (1.37) after
      rehabilitation, and the SGRQ scores at the same times were 27.63 (16.02) and
      25.45 (15.12). Mortality due to respiratory disease (105 months) was 19%.
      Cumulative survival rates at 1 year, 3 years, and 6 years were 91%, 86.7%, and
      6.75%, respectively. Survival was related to an FEV1 greater than 1.02 L (P =
      .05), a 6-minute walk distance over 448 m before rehabilitation (P = .04) and 454
      m after rehabilitation (P = .05), and a workload on the cycle ergometer of over
      54 W before rehabilitation (P = .01) and 72 W (P = .02) afterwards. The
      correlations between survival and both SGRQ and BODE scores were weaker.
      CONCLUSIONS: We observed improved exercise capacity, dyspnea ratings, and, to a
      lesser extent, better SGRQ scores in our COPD patients following pulmonary
      rehabilitation. The best predictors of survival were FEV1, the 6-minute walk
      distance, and the cycle ergometer workloads.

PMID- 17040659
TI  - [Appropriateness of hospital admissions to a pulmonology department].
AB  - OBJECTIVES: To analyze the rate of inappropriate admissions to a pulmonology
      department over the period of a year and to establish the reasons for such
      admission and predictors. PATIENTS AND METHODS: All 2004 admissions to the
      pulmonology department of the Hospital de Valme were analyzed using a version of
      the Appropriateness Evaluation Protocol (AEP) developed for concurrent review.
      Two physicians who were not directly involved in admitting the patients performed
      the review. A logistic regression analysis was performed in order to identify the
      independent predictors of inappropriate hospital admission. RESULTS: Of the 633
      admissions analyzed, 92.1% (n = 583) were appropriate and 7.9% (n = 50) were
      inappropriate. The main reason for considering an admission to be inappropriate
      was that the patients in question could have been managed as outpatients (70%),
      whereas appropriate admissions were most frequently justified by the need for
      parenteral treatment (76.3%) or respiratory therapy (62%). In the logistic
      regression analysis, the variables that were independently associated with
      inappropriate admission were nonurgent admission (odds ratio, 2.82; 95%
      confidence interval, 1.28-6.21; P = .01), and a neoplasia diagnosis as the reason
      for admission (odds ratio, 8.57; 95% confidence interval, 2.69-27.24; P < .0005).
      CONCLUSIONS: The rate of inappropriate hospital admissions was lower than that
      reported in other studies. Most inappropriate admissions were of patients who
      could have been managed as outpatients. An admission diagnosis of neoplasm and
      nonurgent admission were independent predictors of inappropriateness.

PMID- 17040660
TI  - [The EpicliCP-2003 study: A multicenter epidemiological and clinical study of
      lung cancer in Spain].
AB  - OBJECTIVE: Mortality due to lung cancer in Spain is increasing continuously. The
      aim of the present study was to collect information on the hospital incidence of
      lung cancer, as well as information on clinical management, in different regions
      of Spain. MATERIAL AND METHODS: A prospective observational study of patients
      diagnosed with lung cancer in 2003 was carried out in 13 centers in 9 autonomous
      communities. Epidemiological, clinical, diagnostic, and therapeutic variables
      were assessed. RESULTS: Of a total population of 2,726,601 inhabitants (1 346 483
      men and 1 380 118 women), 1064 male and 125 female lung cancer patients were
      included. The incidence standardized to the world population varied between
      42.4/100,000 and 61.8/100,000 in men and between 1.5/100,000 and 8.6/100,000 in
      women. Overall, 51% were aged over 70 years, and 97.5% of the men and 32% of the
      women were smokers or ex-smokers. Cytologic or histologic confirmation was
      obtained for 93.1% of the cases (20.8% of which were small cell lung cancers and
      79.2% were non-small cell lung cancers). The main initial symptoms were cough,
      chest pain, and weight loss. In 13.7%, lung cancer was suspected because of
      abnormal chest x-ray. The percentage with clinical TNM stages I and II ranged
      from 6.3% to 26.9%. The most common stage was stage IV in all centers. The
      percentage of patients undergoing surgery ranged from 2.5% to 20.6%, with a mean
      of 14.8% (19.9% of whom were patients with non-small cell lung cancer); 27%
      received palliative treatment only. CONCLUSIONS: The proportion of women
      suffering from lung cancer increased with respect to previous studies, with
      notable differences among regions. Despite diagnostic improvements, the
      percentage of patients undergoing surgery is low, though interregional variation
      is considerable.

PMID- 17040661
TI  - [Assessing the risk of asthma in infants and pre-school children].
AB  - Childhood asthma is a heterogeneous inflammatory disease with several wheezing
      phenotypes (transient, atopic, nonatopic, and obese) and various clinical
      expressions of multifactorial origin. All forms, however, follow a similar course
      characterized by recurrent episodes of airway obstruction. Studies have shown
      that the onset of disease occurs early in life for the great majority of
      asthmatics, that airway inflammation and remodeling are present in schoolchildren
      with asthma, and that even infants with persistent wheezing present airway
      inflammation. The difficulty lies in the early identification of infants with
      recurrent wheezing who are at risk of suffering persistent asthma later in life.
      The Asthma Predictive Index, a simple tool validated in a longitudinal study, has
      been suggested for early identification of infants with recurrent wheezing who
      are at risk of developing asthma and whose lung function has undergone major
      irreversible damage during the first years of life.

PMID- 17040662
TI  - [Guidelines for occupational asthma].

PMID- 17040663
TI  - [Hepatopulmonary syndrome in a patient with adenocarcinoma of the colon
      metastatic to the liver and no apparent chronic liver disease].
AB  - Hepatopulmonary syndrome consists of a clinical triad: arterial blood
      deoxygenation, intrapulmonary vasodilation, and liver disease. Both acute and
      chronic cases of this syndrome have been reported, and the most common cause is
      cirrhosis. The principle disease mechanism is dilation of the pulmonary blood
      vessels causing alterations in gas exchange. Increased pulmonary production of
      nitric acid has been implicated as the primary pathogenic mechanism of
      vasodilation although it has also been associated with imbalance between
      vasodilators and vasoconstrictors. We describe the case of a patient with
      hepatopulmonary syndrome and adenocarcinoma of the colon with metastases to a
      previously healthy liver.

PMID- 17040664
TI  - [A simple air travel fitness test for patients with chronic cardiorespiratory
      disease].

PMID- 17040665
TI  - [On lithoptysis and the limitations of bibliographic databases].

PMID- 17040666
TI  - [Fast-track surgery: the facts and the challenges].

PMID- 17040667
TI  - [Robotics and laparoscopic surgery].
AB  - Laparoscopic surgery has completely revolutionized modern surgery. In addition to
      its advantages, however, this approach also presents significant limitations. The
      most important are loss of the sense of depth, tactile sensation and resistance,
      as well as loss of natural hand-eye coordination and manual dexterity. The main
      motivation for the development of surgical robots is the possibility of
      eliminating all these limitations. Robots have acquired great potential to
      improve the operative possibilities of surgeons. Given the continual increase in
      the use of surgical robots, in the near future the structure and appearance of
      current operating rooms will change. The present article analyzes the origin and
      development of robotic systems, as well as the characteristics of the latest
      generation of robots. Because of the strong interest in robotic surgery and its
      future prospects, surgeons should be familiar with these emerging and innovative
      techniques.

PMID- 17040668
TI  - [Computerized physician order entry of pharmacotherapeutic protocols in a
      colorectal surgery unit].
AB  - INTRODUCTION: Computerized physician order entry was introduced in our hospital.
      We present the pharmacotherapeutic protocols that we use in patient care.
      MATERIAL AND METHODS: Six pharmaceutical protocols were designed by consensus in
      a colorectal surgery unit and were applied over a 2-year period. Patients
      undergoing ambulatory or urgent surgery were excluded. RESULTS: We treated 772
      patients. Two hundred twenty patients (28.5%) were assigned to the preoperative
      protocol for minor proctologic surgery. After surgery, all 220 patients were
      included in the postoperative protocol for minor proctologic surgery. The
      remaining 552 patients (71.5%) were assigned to the protocol for major colorectal
      surgery. The preoperative protocol for major colorectal surgery was indicated in
      542 patients (98.2%) and its variant for patients allergic to beta-lactam
      antibiotics was used in 10 patients (1.8%). The postoperative pharmacotherapeutic
      protocol assigned depended on whether a central venous line (317 patients; 57.4%)
      or only peripheral venous access (235 patients; 42.6%) was used. CONCLUSIONS:
      Each clinical unit has a duty to carry out and update consensus protocols (always
      based on the best scientific evidence available) that can be used in the
      processes managed in that unit. The use of these protocols shows a high degree of
      acceptance among physicians and nurses, allowing clinical practice to be
      standardized and healthcare processes to be homogenized.

PMID- 17040669
TI  - [Intraoperative therapeutic intensification techniques in locally advanced
      abdominal sarcomas].
AB  - INTRODUCTION: Sarcomas are rare tumors that develop from mesenchymal cells. Their
      management is difficult due to their changing histology, location, and behavior.
      In this article, we discuss the use of two intraoperative therapeutic
      intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic
      intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally
      advanced abdominal sarcomas and peritoneal sarcomatosis. MATERIAL AND METHODS: We
      analyzed a series of 20 consecutive patients diagnosed with advanced abdominal
      sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were
      evaluated and treated in our department from December 1996 to October 2005. In
      advanced abdominal sarcoma, we performed complete or maximal resection followed
      by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed
      by HIIC. RESULTS: The survival rate in advanced abdominal sarcomas without
      sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal
      sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow
      up. CONCLUSIONS: IORT associated with radical surgery seems to improve local
      control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus
      HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that
      offers a therapeutic option with curative intent.

PMID- 17040670
TI  - [Thyroidectomy in the ambulatory setting. A prospective study].
AB  - INTRODUCTION: The recent reintroduction of local/regional anesthesia (LRA) for
      thyroidectomy has enabled this intervention to be performed in the outpatient
      setting. The aim of this study was to compare the results of thyroidectomy using
      two anesthesia methods. PATIENTS AND METHODS: One hundred twenty-five patients
      requiring thyroidectomy and who met the criteria for outpatient surgery were
      prospectively selected. The patients were offered LRA plus sedation; patients who
      did not accept this option were offered LRA combined with orotracheal intubation
      (CLRA). LRA was accepted by 58 patients and CLRA by 67. Age, sex, anesthesia
      risk, body mass index, and thyroid function were similar in both groups.
      Postoperative vomiting, pain at discharge, need for admission, postoperative
      morbidity, and complaints occurring at home were evaluated. RESULTS: Sixty-one
      bilateral and 64 unilateral thyroidectomies were performed, with no statistically
      significant difference between the two groups. There were no differences in
      surgical time, conversion to general anesthesia, intraoperative events,
      pathological diagnosis, or size and weight of the surgical specimen. The only
      difference between the two groups was the hour of discharge (LRA: 6.5 +/- 1.2
      hours; CLRA: 7.76 +/- 2.07 hours; p = 0.0003). The admission rate was higher in
      the CLRA group (22.4%) than in the LRA group (8.62%); this difference was not
      statistically significant (p = 0.06) and the main cause was personal preference
      in patients in the CLRA group. Rates of postoperative morbidity, vomiting (7.2%)
      and nausea (6.4%), postoperative pain (2.47 +/- 1.85 on a visual analog scale),
      and analgesic requirements showed no differences between the two groups. One
      patient in the LRA group developed a noncompressive asymptomatic neck hematoma 36
      hours after discharge. The patient was admitted for observation but did not
      require reoperation. Complaints occurring at home were minor. Satisfaction with
      the procedure was high or very high in 95% of the patients, with no differences
      between the two groups. CONCLUSIONS: In selected patients, outpatient
      thyroidectomy is safe and produces good patient satisfaction. Both anesthesia
      methods were valid, but postoperative recovery was faster with LRA than with
      CLRA.

PMID- 17040671
TI  - [Prevention of peritoneal adhesions to intraperitoneal prostheses. An
      experimental study in pigs].
AB  - INTRODUCTION: The aim of this study was to investigate the effect of fibrin glue
      and hyaluronidase gel on the prevention of postoperative peritoneal adhesions to
      intraperitoneal prostheses. MATERIAL AND METHOD: Twenty pigs, divided in two
      groups, were included. In all animals, four implants (4 x 4 cm) were placed: two
      polypropylene mesh implants were placed in an upper location and two
      polytetrafluoroethylene (PTFE) implants (Dualmesh Plus Corduroy) were placed in a
      lower position. Implants located in the right side of the animals were painted
      with fibrin glue (group A, n = 10) or with hyaluronidase gel (group B, n = 10).
      After 5 weeks, the animals were sacrificed and the results (number and grade of
      intraperitoneal adhesions, histological data on prosthesis integration, such as
      mesothelialization, fibroblast infiltration, vessel neoformation, etc.) were
      evaluated. RESULTS: Intraperitoneal adhesions decreased in implants painted with
      fibrin glue and hyaluronidase gel compared with untreated implants. When right
      sided adhesions formed, they were looser and in many animals, the implants were
      completely peritonized. Integration of the prostheses was not affected by either
      fibrin glue or hyaluronidase gel. CONCLUSIONS: Adhesion formation can be reduced
      after abdominal surgery. The reduction achieved in this study was greater in the
      quantity than in the consistency of the adhesions. The results with hyaluronidase
      gel were moderately superior to those obtained with fibrin glue. Hyaluronidase
      gel has the advantage of being inexpensive.

PMID- 17040672
TI  - [Use of pneumoperitoneum in the repair of giant abdominal hernias].
AB  - The preoperative use of progressive pneumoperitoneum has been demonstrated to be
      safe and effective in the treatment of large hernias. The indications for this
      technique include massive hernias, hernias in patients with high surgical risk,
      and large recurrent hernias. We describe four patients in whom progressive
      pneumoperitoneum was carried out under local anesthesia and sedation between 1
      and 3 weeks before surgery. All four hernias were closed with a preperitoneal
      mesh. Insufflation was performed on an inpatient basis in two patients and in the
      ambulatory setting in one. No postoperative complications were detected. No
      evidence of recurrence was found during follow-up (10 months-11 years).

PMID- 17040674
TI  - [Sequelae after illegal injection of liquid silicone for breast augmentation:
      report of two cases].
AB  - The use of liquid silicone for breast augmentation was widespread in the 1960s
      but was abandoned at the end of the decade due to numerous studies describing the
      development of a large number of local complications, as well as remote migration
      of small amounts of silicone. The use of liquid silicone also leads to enormous
      difficulty in the early diagnosis of breast cancer; these patients are precluded
      from routine screening programs and must undergo exhaustive periodic
      examinations. Magnetic resonance imaging has become the most effective test for
      the early detection of breast cancer in these patients. Indications for
      subcutaneous mastectomy are the presence of local complications, suspicion of a
      malignant lesion, or the patient's desire to prevent both these potential
      problems.

PMID- 17040673
TI  - [Traumatic perforation of a duodenal diverticulum].
AB  - Duodenal diverticulum is a frequent abnormality that is usually diagnosed
      incidentally. Clinical manifestations usually mimic highly varied entities. Among
      the complications of duodenal diverticulum, perforation is fairly rare and
      rupture due to blunt trauma is even rarer. We describe the case of a male patient
      who presented a perforated duodenal diverticulum after an accidental fall.

PMID- 17040675
TI  - [Image of the month].

PMID- 17040676
TI  - [Presacral solitary fibrous tumor:a difficult diagnosis and an infrequent
      location].

PMID- 17040678
TI  - Amoebiasis: new understanding and new goals.

PMID- 17040677
TI  - [Video-assisted thoracoscopy with intraoperative Tc-MIBI scintigraphy].

PMID- 17040680
TI  - Urinary antigen detection for diagnosis of parasitic infections.

PMID- 17040679
TI  - Resources available from the african trypanosome genome project.

PMID- 17040681
TI  - Malaria, microtubules and merozoite invasion.

PMID- 17040682
TI  - Llamas, lectures and health inspectors on the web.

PMID- 17040683
TI  - Santa rosalia revisited: or why are there so many kinds of parasites in ;the
      garden of earthly delights'?
AB  - As is the case for free-living species, a very large number of parasitic species
      are not described adequately by the biological species concept. Furthermore,
      Thierry de Meeus, Yannis Michalakis and Francois Renaud argue that because hosts
      represent a highly heterogeneous and changing environment as well as a breeding
      site, favouring the association of host-adaptation and host-choice genes,
      sympatric speciation may occur frequently in parasitic organisms. Therefore,
      parasites appear to be ideal biological models for the study of ecological
      specialization and speciation. Beyond the relevance of such considerations in
      fundamental science, the study of the origin and evolution of parasite diversity
      has important implications for more applied fields such as epidemiology and
      diagnosis.

PMID- 17040684
TI  - Waterborne cryptosporidiosis: current status.
AB  - In the past ten years Cryptosporidium oocysts have been shown to be common
      contaminants of water, causing at least 19 waterborne outbreaks of
      cryptosporidiosis which have affected more than 427 000 individuals. Recommended
      methods for oocyst isolation and enumeration are time-consuming and inefficient
      and experts state that the absence of Cryptosporidium oocysts in drinking water
      can never be guaranteed. In the UK alone, a National Research Programme costing
      pound3 million has been undertaken. Here, Huw Smith and Joan Rose review the
      current status of knowledge and identify approaches taken by UK and USA
      Government regulatory bodies in order to reduce the likelihood of waterborne
      transmission.

PMID- 17040685
TI  - Puberty and Age-related Changes in Susceptibility to Schistosome Infection.
AB  - Recent data from outbreaks of schistosomiasis in immunologically naive
      populations have refuelled the debate concerning the nature or existence of
      protective, acquired immunity to schistosomiasis in humans. Data from endemic
      communities provide some compelling evidence for an abrupt change in reinfection
      rates that coincides with puberty. We suggest that the hormonal changes of
      adrenarche may hold the key to understanding the relative resistance to infection
      found in adults.

PMID- 17040686
TI  - Heterotrimeric Guanine Nucleotide-binding Proteins in Eukaryotic Parasites.
AB  - Parasites, in order to survive, must be able to recognize and respond to signals
      in their environment. This is particularly so when parasite development is
      associated with moving from one environment to another as it is likely that a
      rapid process of adaptation that requires changes in gene expression will have to
      be initiated. In general, interaction with host signals takes place at the
      parasite surface, with the resulting need for information to be trasmitted to the
      interior. Many such signalling events in mammalian cells are regulated by a
      family of molecules referred to as guanine nucleotide-binding proteins (G
      proteins). The structure and function of these molecules, and evidence obtained
      to date of the roles that they may play in parasitic organisms, are discussed
      here by Bill and Maggie Harnett.

PMID- 17040687
TI  - Leishmania amastigote target antigens: the challenge of a stealthy intracellular
      parasite.
AB  - The development of a defined molecular vaccine against leishmaniasis involves the
      determination of candidate molecules that elicit protection against infection. As
      the amastigote stage is the developmental form found in the infected mammalian
      host, molecules specific to or upregulated in this stage represent potential
      antigenic vaccine targets. Diane McMahon-Pratt, Peter Kima and Lynn Soong
      summarize experiments which indicate that immunization with molecules upregulated
      in the amastigote stage can provide effective protection against infection. In
      the immunized host, both CD4(+) and CD8(+) T cells appear to be crucial to
      protection. Studies of antigen presentation of Leishmania-infected macrophages
      indicate that the amastigote stage can sequester endogenous leishmanial antigen
      from the major histocompatability complex (MHC) class II presentation pathway.
      However, evidence indicates that MHC class I presentation may be sustained in the
      infected macrophage. The effect of these findings on the design of a leishmanial
      vaccine are considered.

PMID- 17040688
TI  - Trichinellosis in the European union: epidemiology, ecology and economic impact.
AB  - Trichinellosis, one of the most widespread helminthic zoonoses, is still endemic
      in most countries of the European Union. In the past few years, advanced
      biotechnology has been used to re-examine the taxonomy, epidemiology and life
      cycles of aetiological agents, providing additional information on the main
      factors contributing to the maintenance of these parasites in Nature. The old
      concept that pigs and rats are the main hosts of Trichinella spiralis, as still
      reported in many books, has been re-evaluated thoroughly. In this review, Edoardo
      Pozio summarizes the epidemiology and ecology of human and animal trichinellosis,
      quantifies the economic impact of this zoonosis and suggests methods of
      controlling this infection that would result in a great reduction in costs.

PMID- 17040689
TI  - Biology of giant proteins of Plasmodium: resolution on polyacrylamide-agarose
      composite gels.
AB  - The malaria parasite Plasmodium falciparum that infects humans encodes several
      extremely large proteins with molecular masses in the hundreds of thousands to
      megadalton range. Studies on the structure, function and antigenicity of these
      ;giant proteins' are hindered by the inability to resolve them effectively in
      conventional polyacrylamide gels. In this report, Jochen Wiesner, Denise Mattei,
      Artur Scherf and Michael Lanzer describe a convenient gel system, based on a
      composite polyacrylamide-agarose matrix, which facilitates analysis of giant
      proteins.

PMID- 17040690
TI  - Epitope tagging in leishmania: testing of commercial monoclonal antibodies.

PMID- 17040691
TI  - Malaria, microtubules and merozoite invasion: reply.

PMID- 17040692
TI  - Analytical parasitology.
AB  - edited by M.T. Rogan, Springer, 1997. DM128.00 (365 pages) ISBN 3 540 58919 8.

PMID- 17040693
TI  - Toxoplasmosis: from clinics to basic science.

PMID- 17040694
TI  - Multiparasitism, Production and Economics in Domestic Animals in sub-Saharan West
      Africa.
AB  - Over the past ten years, an informal West African animal helminthosis network has
      developed (), with the aims of both improving livestock productivity through
      parasite control and, ultimately, increasing rural income. The network places a
      strong emphasis on building up local research capacity through scientific
      partnership. This article highlights recent findings from projects of the
      network.

PMID- 17040695
TI  - Can Trypanosoma Trees be Trusted?

PMID- 17040696
TI  - Indigestion, not scorched Earth, beats alien hookworms?

PMID- 17040697
TI  - Hookworm-induced Hypersensitivity: A Response.

PMID- 17040698
TI  - ParaSite: The Pick of Parasites on the Web.
AB  - While a steady flow of questions were put to the general parasitology newsgroup
      during November, none provoked discussion. Other discussion lists came to life:

PMID- 17040699
TI  - Malaria vaccine development: current status.
AB  - The development of an effective malaria vaccine represents one of the most
      important approaches that would provide a cost-effective intervention for
      addition to currently available malaria control strategies. Here, Howard Engers
      and Tore Godal review recent advances. Over the past decade there has been
      considerable progress in the understanding of immune mechanisms involved in
      conferring protection to malaria and in the identification of vaccine candidate
      antigens and their genes. Several new vaccines have entered Phase I/II trials
      recently, new adjuvants have been developed for human use and new approaches,
      such as DNA vaccines and structural modification of antigens to circumvent some
      of the strategies the parasite uses to avoid the immune response, are being
      applied. Thus, from the TDR perspective, global malaria vaccine development is
      entering a crucial period with unprecedented opportunities.

PMID- 17040700
TI  - Histone genes in trypanosomatids.
AB  - Histone genes in Trypanosomatids are of considerable interest because these
      flagellates do not condense their chromatin during mitosis. In contrast to higher
      eukaryotes, histone genes in Trypanosomatids are found on separate chromosomes,
      and their transcripts are polyadenylated. Sequence similarity of Trypanosomatid
      core histones with those of higher eukaryotes is found predominantly in the
      globular region; the N-terminal is highly divergent. Finally, in general,
      Trypanosomatid histones H1 are of low molecular weight, bearing closest homology
      to the C-terminal region of the higher eukaryote histones H1. These features
      constitute interesting targets for a rational approach to the study of these
      protozoa, as discussed here by Norbel Galanti and colleagues.

PMID- 17040701
TI  - Hookworm-provoked IgE-mediated Pathology: Capricious Damage or Remarkable
      Strategy?
AB  - The existence of the canine hookworm Ancylostoma caninum in the human gut seems
      to be curtailed by an effective IgE-mediated inflammatory response against the
      helminth's feeding secretions, which, by damaging the host, compromises the
      parasite's feeding opportunities. In contrast, immunity does not develop against
      adapted, anthropophilic hookworm species, and it is suggested this relates to
      modulation of the inflammatory response by hookworm secretions. Here, John Croese
      discusses this hypothesis and its implications for the development of drugs to
      suppress allergy.

PMID- 17040702
TI  - Muscling in on parasitic flatworms.
AB  - The musculature of parasitic platyhelminths (monogeneans, digeneans and cestodes)
      presents an attractive target for chemotherapeutic intervention in that it is
      central to locomotory movement and attachment and serves an essential role in
      alimentation (feeding, translocation of food and digestive waste) and
      reproduction (insemination, egg formation and oviposition). Here, Gunnar Mair,
      Aaron Maule, Chris Shaw and David Halton review muscle organization in flatworm
      parasites, and outline some of the recent physiological and molecular advances
      that have been made in flatworm muscle research.

PMID- 17040703
TI  - Trypanosomiasis and Tsetse Control with Insecticidal Pour-ons- Fact and Fiction?
AB  - Insecticidal pour-ons that are applied directly to cattle have been promoted
      widely in the last decade as a new means of controlling tsetse flies in Africa.
      Tsetse attracted to treated cattle get a lethal dose of insecticide and die.
      Following a large trial in Kenya, Matthew Baylis and Peter Stevenson argue here
      that the reduction in trypanosomiasis incidence caused by pour-ons exceeds that
      expected from the impact (if there is any) on the tsetse population and that
      certain other (as yet unknown) factors must also be involved.

PMID- 17040704
TI  - Re-examining the ;Cycle Concept' in Malaria.

PMID- 17040705
TI  - Reply from stoute et Al.

PMID- 17040706
TI  - Reply from rajan.

PMID- 17040708
TI  - Host-parasite evolution: general principles and avian models.
AB  - edited by D.H. Clayton and J. Moore, Oxford University Press, 1997. pound60.00
      (hbk)/ pound25.00 (pbk) (xi+473 pages) ISBN 0 19 854893 1/0 19 854892/3.

PMID- 17040707
TI  - Plant molluscicides in South Africa: a registration dilemma.

PMID- 17040709
TI  - Standardizing PCR for molecular epidemiology studies of malaria.

PMID- 17040710
TI  - Drug-resistant Parasites of sheep:an emerging problem in the UK?

PMID- 17040711
TI  - Malaria transfection:a new tool to study molecular function.

PMID- 17040712
TI  - Comments and cultures on the internet.

PMID- 17040713
TI  - The USAID/Government of Egypt's Schistosomiasis Research Project (SRP).
AB  - Schistosomiasis is the major public health problem in rural Egypt, with almost
      six million Egyptians infected as at mid-1996. In 1983, the prevalence of
      schistosomiasis in rural Egypt was greater than 50%, but a ten-year campaign of
      diagnosis and treatment has reduced the prevalence and intensity of infection.
      Parallel to this campaign, the government of the USA has funded a research
      project to examine all aspects of schistosomiasis with a view to improving the
      control strategy. As outlined here by Taha El Khoby, Nabil Galal and Alan
      Fenwick, after almost ten years, the project's achievements include: assisting
      WHO in its attempts to develop a vaccine against schistosomiasis, developing a
      suspension formulation of praziquantel suitable for young children, and
      establishing a unit to monitor reports of resistance to praziquantel. In
      addition, a large epidemiological study has established the extent of the problem
      in Egypt. Slow-release formulation of niclosamide, health education material for
      use on TV, dipstick diagnostic tests, and evaluation of ultrasound as a
      diagnostic tool have also been achieved. As the project closes, Egypt is left
      with an effective strategy for the control of schistosomiasis and several back-up
      tools for use in the event of development of resistance to praziquantel. The
      Ministry of Health and Population has the basis of a Geographical Information
      System (GIS) unit and the country has a trained and equipped scientific community
      capable of biomedical research, and almost 100 scientific papers published on
      their work.

PMID- 17040714
TI  - Why don't we have a schistosomiasis vaccine?
AB  - Over the past 30 years there has been a concerted effort to understand host
      immune responses to schistosomes, with the ultimate aim of producing a vaccine
      for human use. In this issue, Bergquist and Colley, in summarizing recent
      meetings in Cairo, provide a detailed appraisal of progress towards that goal. It
      seems an appropriate time to ask why, with reference to Schistosoma mansoni, the
      development of a vaccine has proved so difficult. This question is explored here
      by Alan Wilson and Pat Coulson.

PMID- 17040715
TI  - Schistosomiasis vaccine:research to development.
AB  - In this article, Robert Bergquist and Dan Colley deal with the consolidated,
      international efforts to generate a schistosomiasis vaccine; in particular, they
      summarize the deliberations of a series of meetings, held in Cairo, Egypt, 21-25
      May 1997, with the aim of reviewing the current status of affairs in this respect
      in order to make recommendations for the future course of schistosomiasis vaccine
      development.

PMID- 17040716
TI  - A Vaccine for Schistosomiasis: alternative approaches.
AB  - An independent trial of candidate antigens for a Schistosoma mansoni vaccine has
      been completed recently under the auspices of the World Health Organization TDR
      programme. It has been acknowledged that the results of the trial failed to meet
      expectations and, therefore, it is appropriate that the options for future work
      should be considered. In this article, Mike Doenhoff describes two S. mansoni
      molecules-a schistosome larval protease and a high molecular weight egg and worm
      antigen. Both are associated with protective immunity, but they have unusual
      immunological properties that distinguish them from the antigens tested so far.
      The results suggest that alternative approaches to a schistosomiasis vaccine are
      still worth exploring.

PMID- 17040717
TI  - Vaccination against Schistosomiasis: The case for Lung-stage Antigens.
AB  - The development of an effective vaccine against human schistosomiasis remains a
      highly desirable yet elusive goal. In this article, Adrian Mountford and Richard
      Harrop focus attention on an approach that aims to identify proteins from
      Schistosoma mansoni that are capable of stimulating protective Th1 cell-mediated
      immune responses. They propose that the most likely source of such antigens is
      the lung-stage schistosomulum.

PMID- 17040718
TI  - The Role of Microscopy in the Investigation of Paramyosin as a Vaccine Candidate
      against Schistosoma japonicum.
AB  - There has been growing interest in paramyosin as a vaccine component to combat
      schistosomiasis. Immunological and molecular techniques have been used in the
      past to investigate the effectiveness of a paramyosin vaccine as an anti
      schistosomal treatment. However, recent localization studies at ultrastructural
      and morphological levels have highlighted a number of questions concerning the
      role of paramyosin within schistosome parasites. Debates about how a non-surface
      protein such as paramyosin might provide protection against schistosome
      infections have recently been addressed by microscopy results. Immunolocalization
      studies have indicated multiple functions of paramyosin within the parasite and
      provided insights into how a vaccine may target the parasite, as discussed here
      by Geoffrey Gobert.

PMID- 17040719
TI  - Genetic Variability of Trypanosoma cruzi:Implications for the Pathogenesis of
      Chagas Disease.
AB  - Chagas disease, caused by the protozoan Trypanosoma cruzi, has a variable
      clinical course, ranging from symptomless infection to severe chronic disease
      with cardiovascular or gastrointestinal involvement or even overwhelming acute
      episodes. The factors influencing this clinical variability have not been
      elucidated, but genetic variation of both the host and parasite is likely to be
      important. Here, Andrea M. Macedo and Sergio D.J. Pena review the evidence
      showing a role for the genetic constitution of T. cruzi in determining the
      clinical characteristics of Chagas disease, and propose a ;clonal-histotropic
      model' for the pathogenesis of this disease.

PMID- 17040720
TI  - Echinococcus granulosus: Contamination of Hydatid Cysts with Eggs and Larvae of
      the Nematode Muellerius capillaris.

PMID- 17040722
TI  - Malaria transfection: a new tool to study molecular function-reply.

PMID- 17040721
TI  - Diagnostic medical parasitology.
AB  - by L.S. Garcia and D.A. Bruckner, ASM Press, 1997. pound60.00 (xv+937 pages) ISBN
      1 55581 1167.

PMID- 17040723
TI  - Net gain: a new method for preventing malaria deaths.
AB  - edited by C. Lengeler, J. Cattani and D. de Savigny, IDRC, 1996. $30.00 (189
      pages) ISBN 0 88936 792 2.

PMID- 17040724
TI  - Undergraduate teaching of medical parasitology.

PMID- 17040725
TI  - The african trypanosome genome project:focus on the future.

PMID- 17040726
TI  - Parasitic helminths: from genomes to vaccines.

PMID- 17040727
TI  - Australian parasitological research: now and in 2000.

PMID- 17040728
TI  - Emerging infections: origins, ecology, costs and prevention.

PMID- 17040729
TI  - On ;the efficacy of antifolate antimalarial combinations in Africa'.

PMID- 17040730
TI  - Camels, Cues and Cure-alls on the Net.

PMID- 17040731
TI  - Peroxidoxins: a new antioxidant family.
AB  - Peroxidoxins are a recently described family of antioxidants. They have an
      ancient origin, being present in organisms as primitive as the archaea, and they
      appear to be ubiquitous in living cells. Here, Sharon McGonigle, John Dalton and
      Eric James review the present understanding of the functions and mechanism of
      action of these enzymes and suggest that these antioxidants may represent the
      ;missing link' in the metabolism of reactive oxygen species by some protozoan and
      helminth parasites. Also, by performing sequence comparisons of homologues
      entered in the public databases, they have classified the parasite peroxidoxins
      as 1-cys or 2-cys enzymes. The discovery of these antioxidants may change our
      understanding of how reactive oxygen species, of parasite or host origin, are
      managed by parasites.

PMID- 17040732
TI  - Sexual differentiation and development in the malaria parasite.
AB  - The protozoan parasites belonging to the genus Plasmodium have a complex life
      cycle in which the asexual multiplication of parasites in the vertebrate host
      alternates with an obligate sexual reproduction in the mosquito. Gametocytes
      (male and female) produced in the vertebrate host are responsible for
      transmitting parasites to mosquitoes. Although our understanding of the biology
      and genetics of sexual differentiation in Plasmodium is expanding, the most basic
      questions concerning molecular mechanisms of sexual differentiation and sex
      determination still remain unanswered. Recently, insight into the control of this
      complex process in P. falciparum and P. berghei has come from studying parasite
      mutants with aberrant capacities for gametocyte production. Here, Cheryl-Ann Lobo
      and Nirbhay Kumar review these analyses in P. falciparum.

PMID- 17040733
TI  - Some Opportunistic Parasitic Infections in AIDS: Candidiasis, Pneumocystosis,
      Cryptosporidiosis, Toxoplasmosis.
AB  - Almost 80% of patients with AIDS die from infections other than human
      immunodeficiency virus (HIV). These infections usually occur late in the course
      of disease when CD4(+) T-cell count has fallen below 200 permm(3) cells per
      milliliter. Most of these infections are caused by organisms that do not normally
      afflict healthy individuals and are thus considered to be opportunistic. In this
      article, Lloyd Kasper and Dominique Buzoni-Gatel review the host-parasite
      interaction for four important pathogens: Candida albicans and Pneumocystis
      carinii (usually non-invasive pathogens), Cryptosporidium parvum (invades the
      cells but remains localized in the gut) and Toxoplasma gondii (penetrates through
      the gut to cause systemic infection). These organisms, which generally cause
      limited or even insignificant clinical evidence of infection in the normal host,
      were chosen because of their high prevalence in AIDS patients and because they
      exhibit different invasive abilities. The reason why individuals with AIDS are
      susceptible to this particular group of pathogens is uncertain.

PMID- 17040734
TI  - Implications of calreticulin function in parasite biology.
AB  - Calreticulin (CR) is a Ca(2+)-binding, multifunctional protein. The amazing array
      of CR-associated functions range from intracellular activities in secondary
      messenger release, protein folding and the modulation of gene expression to
      potential interactions with host receptors and signaling machinery and
      recognition by the host immune system. The multifunctional nature of CR may
      impact upon the ability of cells to recognize extracellular stimuli and
      coordinate appropriate responses. Identification of CR isolated from parasites
      and the conservation of its functions suggests that investigations into the
      contributions of CR to various aspects of parasite biology should be undertaken
      because it may reveal information regarding parasite interaction with the host
      and how the parasite may modulate its response to the host.

PMID- 17040735
TI  - Parasitic worms: an ally in the war against the superbugs.
AB  - The entomopathogenic nematodes are now of considerable scientific interest not
      only because of their function as biological control agents, but because of the
      potential medical and agricultural importance of the metabolic products of their
      symbiotic bacteria. Initial exploration in Australia, a decade ago, has blossomed
      into a significant area of research activity as we discover the nematicidal,
      anticancer, antimycotic and antibiotic properties of these bacterially derived
      compounds. Some of the antibiotics are novel compounds, and they might form the
      basis of the next round of drugs against the superbugs, as discussed here by John
      Webster, Genhui Chen and Jianxong Li.

PMID- 17040737
TI  - Cross-species Immunity in Malaria.

PMID- 17040736
TI  - Representation of differential expression: a new approach to study differential
      gene expression in trypanosomatids.
AB  - During the past five years, several methods have been described that allow the
      isolation and cloning of stage-specific or cell-specific genes. The
      characterization of genes expressed at different stages of parasite development
      is of the utmost importance for the understanding of the mechanisms involved in
      the regulation of gene expression. Here, Samuel Goldenberg and Marco Aurelio
      Krieger describe a method for the amplification and cloning of Trypanosoma cruzi
      genes expressed specifically at different times of the metacyclogenesis process.
      This method, representation of differential expression (RDE), should be useful
      for the isolation and cloning of any trypanosomatid gene transcribing
      differentially expressed messenger RNA.

PMID- 17040738
TI  - Is data gathering the only acceptable approach to biological science?

PMID- 17040739
TI  - Leishmania (sauroleishmania): a comment on classification.

PMID- 17040740
TI  - Atlas of Human Parasitology, 4th edn.
AB  - by Lawrence Ash and Thomas Orihel, American Society of Clinical Pathologists,
      Chicago, $155.00 (410 pages) ISBN 0 89189 399 7.

PMID- 17040741
TI  - La Specificite Parasitaire et ses Incidences sur l'Etiologie et l'Epidemologie
      des Parasitoses Humaines d'Origine Zoonotique.
AB  - by J. Euzeby, Fondation Merieux, 1997. 250.00FFr (153 pages) ISBN 2 84039 053 1.

PMID- 17040742
TI  - Mosquitoes and monsoon.

PMID- 17040743
TI  - Integrated Control of Ticks and Tick-borne Diseases (ICTTD).

PMID- 17040744
TI  - The Role of Variant-specific Immunity in Asymptomatic Malaria Infections:
      Maintaining a Fine Balance.

PMID- 17040745
TI  - Trypanosoma cruzi: How Many Relevant Phylogenetic Subdivisions are There?

PMID- 17040746
TI  - Parasite: ;soft' science and something fishy on the net.

PMID- 17040747
TI  - The ribosomal DNA plasmids of entamoeba.
AB  - In most organisms, the nuclear ribosomal RNA (rRNA) genes are highly repetitive
      and arranged as tandem repeats on one or more chromosomes. In Entamoeba, however,
      these genes are located almost exclusively on extrachromosomal circular DNA
      molecules with no clear evidence so far of a chromosomal copy. Such an uncommon
      location of rRNA genes may be a direct consequence of cellular physiology, as
      suggested by studies with Saccharomyces cerevisiae mutants in which the rDNA is
      extrachromosomal. In this review, Sudha Bhattacharya, Indrani Som and Alok
      Bhattacharya summarize current knowledge on the structural organization and
      replication of the Entamoeba rDNA plasmids. Other than the rRNAs encoded by these
      molecules, no protein-coding genes (including ribosomal protein genes) are found
      on any of them. They are unique among plasmids in that they do not initiate
      replication from a fixed origin but use multiple sites dispersed throughout the
      molecule. Further studies should establish the unique biochemical features of
      Entamoeba that lead to extrachromosomal rDNA.

PMID- 17040748
TI  - Ticks are not Insects: Consequences of Contrasting Vector Biology for
      Transmission Potential.
AB  - Quantitative analyses of vector-borne parasite systems are dominated by insect
      systems. In attempts to formulate general statements concerning vectors and their
      indirectly transmitted parasites, ticks are usually ignored or they are
      implicitly or explicitly assumed to obey the same rules as insects. Here, Sarah
      Randolph shows that contrasting biological attributes of these two different
      arthropod classes (ticks and insects) directly affect their performance as
      vectors. The equations for estimating their respective potential to transmit
      parasites differ in important respects, as does the relative impact of each
      factor on these estimates. These conclusions direct attention towards the
      empirical field data most appropriate for quantifying the spatially and
      temporally variable risk of infection from these contrasting vector-borne
      parasite systems.

PMID- 17040749
TI  - Corrigendum: Engers, H.D. and Godal, T. Malaria vaccine development: current
      status. Parasitol. Today 14, 56-64, 1998.

PMID- 17040750
TI  - Determinants of Life-history Evolution in Nematodes.
AB  - What are the determinants of parasite life-history evolution? Does life-history
      evolution of parasitic species differ from their free-living relatives? How and
      why do host and parasite life-history traits covary? Here, Serge Morand and
      Gabriele Sorci use recent comparative studies to investigate life-history
      evolution in nematodes which present both parasitic and free-living groups.
      Application of life-history theory to nematodes suggests that the conventional
      wisdom concerning the high fecundity of parasitic species could simply be the
      result of the larger body size of the latter when compared with free-living
      forms. The authors also emphasize, with the use of examples, that in most cases
      parasite life-history evolution depends on host features.

PMID- 17040751
TI  - Mating Patterns of Plasmodium falciparum.
AB  - Recent empirical data have enabled a more informed debate over the extent of
      clonality in Plasmodium falciparum populations. Oocyst heterozygosity data reveal
      that the mating structure of malaria populations varies according to the
      transmission intensity. This finding provides a more detailed picture of the
      malaria mating structure than previous conclusions, which were based on indirect
      measures of population mating structure, ie. linkage disequilibrium analyses. In
      this article, Ric Paul and Karen Day discuss aspects of the genetic structure of
      malaria populations as evidenced by oocyst heterozygosity and linkage
      disequilibrium data. They address the difficulties of performing genetic analyses
      of malaria parasite population structure inherent in parasite sampling, why two
      identical parasites are rarely observed in the field and how features of the
      epidemiology determine parasite population structure.

PMID- 17040753
TI  - Chronic malaria infection and vaccines.

PMID- 17040752
TI  - Selection of novel ligands from phage display libraries: an alternative approach
      to drug and vaccine discovery?
AB  - Phage display involves the production and screening of large numbers of random
      peptide sequences of a specific length expressed on the surface of phage
      particles. This approach provides a powerful tool to probe the molecular basis of
      many biological processes, including host-parasite interactions. Phage display
      libraries have been used to study the binding specificity of numerous peptides
      and protein domains. Practical applications include the identification of peptide
      sequences that bind with high affinity to antibodies, enzymes or receptors, and
      that may serve as diagnostics and vaccine or drug candidates. Here, David
      Jefferies outlines the concept of phage display and summarizes recent
      developments in the field, with emphasis on those that may be of interest to
      parasitologists.

PMID- 17040754
TI  - Trypanosoma cruzi: How Many Relevant Phylogenetic Subdivisions are There? Reply.

PMID- 17040755
TI  - The Role of Variant-specific Immunity in Asymptomatic Malaria Infections:
      Maintaining a Fine Balance-Reply.

PMID- 17040756
TI  - Communicable disease epidemiology and control.
AB  - by Roger Webber, CAB International, 1997. pound19.95 (xiv+352 pages) ISBN 0 85199
      138 6.

PMID- 17040757
TI  - Parasites and pathogens effects on host hormones and behavior.
AB  - edited by Nancy E. Beckage, Chapman & Hall, 1997. pound57.00 (338 pages) ISBN 0
      412-07401-X.

PMID- 17040758
TI  - Ronald ross: malariologist and polymath. A biography.
AB  - by Edwin R. Nye and Mary E. Gibson, Macmillan (UK) and St Martin's Press (USA)
      1997. pound48.50 (316 pages) ISBN 0 312 16296 0.

PMID- 17040759
TI  - The malaria consortium: converting expertise and partnerships into operational
      realities.

PMID- 17040760
TI  - Future therapeutic alternatives for combating anaerobic protozoa.

PMID- 17040761
TI  - Control of coccidiosis into the next millennium.

PMID- 17040762
TI  - The SPf66 Malaria Vaccine: What is the Evidence for Efficacy?

PMID- 17040763
TI  - Leishmania cysteine proteinases: virulence factors in quest of a function.

PMID- 17040764
TI  - Life, hope and lecture material from the web.

PMID- 17040765
TI  - Progress in development of liver fluke vaccines.
AB  - Infection of ruminants by Fasciola spp continues to cause large economic losses
      worldwide. Recent results from several laboratories have demonstrated that
      animals can be significantly protected against infection by vaccination with
      defined Fasciola antigens. Apart from reducing fluke burdens, some vaccines can
      elicit a concurrent reduction in parasite egg production. The expectation of a
      commercially feasible vaccine that might also reduce parasite transmission in the
      field is now realistic, although major hurdles still exist. Here, Terry Spithill
      and John Dalton review the results of several recent vaccine trials and discuss
      the future prospects for vaccine development.

PMID- 17040766
TI  - Immune dynamics in the pathogenesis of human lymphatic filariasis.
AB  - Despite the longstanding recognition of the spectral nature of human disease due
      to lymphatic filariasis, immunologists interested in pathogenesis have mostly
      examined patients classified as being at either one extreme pole or the other.
      While the clinically asymptomatic individuals with microfilaremia who sit at one
      pole always have active infection, it has been difficult to define who else on
      the clinical spectrum is actively infected with living adult worms. In this
      review, David Freedman discusses how the ability to measure circulating filarial
      antigen in patient serum has advanced our ability to understand the
      immunopathogenesis of lymphatic filariasis by improving the precision of patient
      classification. Recent work suggests that the presence (or absence) of
      antigenemia, rather than overt clinical manifestations of disease, is closely
      associated with specific cytokine responses. A framework for patient
      classification based on these findings is proposed.

PMID- 17040767
TI  - Microtubule inhibitors as potential antimalarial agents.
AB  - The Steering Committee on Drugs for Malaria (CHEMAL) of the UNDP/World Bank/WHO
      Special Programme for Research and Training in Tropical Diseases (TDR) has
      identified tubulin as a potential drug target, but one that is not yet
      ;validated'. Several inhibitors of tubulins, the principal proteins of
      microtubules, are potent inhibitors of the development and multiplication of
      malarial parasites in culture and in vivo. However, most of these compounds are
      also inhibitors of mammalian cell proliferation. Here, Angus Bell reviews the
      structure and properties of microtubules, their roles in Plasmodium cells, and
      the effects of various microtubule inhibitors on the parasite. He argues that
      microtubule inhibitors are not equally toxic to all proliferating cells but, by
      virtue of differential tubulin binding, show selective toxicity that might allow
      their use as antimalarial drugs.

PMID- 17040768
TI  - PCR detection of cryptosporidium: the way forward?
AB  - In this article, Una Morgan and Andrew Thompson briefly review the latest
      information on polymerase chain reaction (PCR)detection of Cryptosporidium parvum
      in both clinical and environmental samples. Current detection methods for
      Cryptosporidium are cumbersome, time-consuming and lack sensitivity. A variety of
      PCR tests have been described recently in the literature and this article
      discusses the advantages and disadvantages of each new technique and their
      potential for future diagnosis of Cryptosporidium.

PMID- 17040769
TI  - Transfection systems for animal models of malaria.
AB  - Transfection of malaria parasites is a rapidly emerging technology that offers
      great promise for the investigation of many aspects of infection. Animal models
      of malaria have always played an important role in the investigation of the
      disease. In this article, two of the Dutch groups that have been involved in
      combining transfection with animal models describe the relevant techniques and
      recent vector developments for the expression of transgenes, giving examples of
      their application.

PMID- 17040771
TI  - Do C3b-CR1 Interactions Contribute to Rosette Formation by Plasmodium falciparum?

PMID- 17040770
TI  - Reply.

PMID- 17040772
TI  - Leishmania cysteine proteinases: virulence factors in quest of a function-reply.

PMID- 17040773
TI  - The SPf66 Malaria Vaccine: Where Do We Go From Here?

PMID- 17040774
TI  - The internet for scientists.
AB  - by Kevin O'Donnell and Larry Winger, Harwood Academic Publishers, 1997.
      pound14.50 (pbk)/ pound30.00 (hbk) (xi+309 pages) ISBN 90 5702 221 4.

PMID- 17040775
TI  - Insect-parasite interactions:reciprocal manipulation.

PMID- 17040776
TI  - Malaria vaccine research and testing in Africa.

PMID- 17040777
TI  - Medical malacology in Africa.

PMID- 17040778
TI  - Malaria mortality: the pacific enigma.

PMID- 17040779
TI  - Preferences, protocols and protection on the web.

PMID- 17040780
TI  - Gene Transcription in Trichomonas vaginalis.
AB  - Since the cloning of the first gene from the flagellated, parasitic protist
      Trichomonas vaginalis in 1990, at least a partial sequence has been obtained from
      over 100 genes. Molecular and biochemical analyses using these genes have
      enhanced our understanding of metabolism, organelle biogenesis, drug
      susceptibility, phylogeny and basic properties of transcription in trichomonads.
      Here, David Liston and Patricia Johnson discuss the available data on the
      regulation of transcription of protein-coding genes in T. vaginalis.

PMID- 17040781
TI  - Differences in energy metabolism between trypanosomatidae.
AB  - Although various members of the family Trypanosomatidae generate energy in a
      similar way, fundamental differences also exist and are not always recognized. In
      this review, Louis Tielens and Jaap Van Hellemond discuss the known differences
      in carbohydrate metabolism among trypanosomatids, and especially compare
      Leishmania with trypanosomatids such as Trypanosoma brucei and Phytomonas spp.
      Special attention will be paid to differences in end-products of carbohydrate
      degradation, to differences in anaerobic capacities between the various
      trypanosomatids and to the components of their respiratory chains, including the
      presence or absence of a plant-like alternative oxidase. Furthermore, evidence
      will be discussed which indicates that the succinate produced by trypanosomatids
      is formed mainly via an oxidative pathway and not via reduction of fumarate, a
      process known to occur in parasitic helminths.

PMID- 17040782
TI  - Protection against Cryptobia (Trypanoplasma) salmositica and Salmonid
      Cryptobiosis.
AB  - Cryptobia (Trypanoplasma) salmositica is a haemoflagellate that causes morbidity
      and mortality in salmon, Oncorhynchus spp, on the Pacific coast of North America.
      In this review, Patrick Woo briefly describes the pathogen, its transmissions
      (either indirectly via its leech vector, Piscicola salmositica, or directly
      between fish) and the clinical signs of the disease. He then outlines strategies
      that have been developed to protect fish against the pathogen, and the mechanism
      of innate resistance to disease in Cryptobia-tolerant fish. Protective strategies
      include the breeding of fish that are resistant to infection, and the use of an
      attenuated C. salmositica strain to protect susceptible fish from disease for at
      least two years. He ends the review with suggestions for further research that
      include the use of the leech vector to deliver the vaccine and the development of
      more novel protective strategies (eg. immunochemotherapy, anti-idiotype vaccine)
      against cryptobiosis.

PMID- 17040783
TI  - Purine stress in crithidia: adaptation of a parasite to environmental stress.
AB  - How parasitic protozoa survive varying nutrient levels is a key issue in
      parasitology. Here, Annette Gero explains how the Trypanosomatid Crithidia
      luciliae responds to purine stress by increasing the rates of transport of
      nucleosides and bases from the environment and by increasing the activity of the
      ectoenzyme 3'-nucleotidase (3'NTase), which breaks down external nucleotides so
      that they can be salvaged as nucleosides. The increase in activity of the purine
      transporters, and the 3'NTase activity is simultaneous with a general increase in
      the purine metabolic pathway, hence ensuring that purines are readily available
      to the parasite during purine stress.

PMID- 17040784
TI  - Virulent Avian Giardia duodenalis Pathogenic for Mice.
AB  - Early in 1995, a sulphur-crested cockatoo captured in the wild died along with
      several other cage mates, apparently of an overwhelming, acute infection of
      Giardia. Trophozoites isolated from the dead bird and established in traditional
      Giardia axenic medium were infective to mice and established chronic infections
      associated with weight gain impairment. Genetically and morphologically, the
      Giardia isolated from the bird belonged to the duodenalis group. Here, Jacqui
      Upcroft, Ann McDonnell and Peter Upcroft present data on pathogenic avian Giardia
      with he potential to contaminate watersheds and discuss the implications.

PMID- 17040785
TI  - Do antioxidants play a role in schistosome host-parasite interactions?
AB  - Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in
      close contact with host humoral and cellular cytotoxic factors. To establish
      itself in the host, the schistosome has evolved a number of immune evasion
      mechanisms. Here, Philip LoVerde discusses evidence suggesting that antioxidant
      enzymes provide one such mechanism used by adult schistosomes. Antioxidant
      enzymes may thus represent a target for immune elimination of adult worms.

PMID- 17040786
TI  - Vintage helminths yield valuable molecules.
AB  - Museum and archival collections of parasites are available throughout the world
      but, although they represent a huge diversity of species and forms, they tend to
      be used solely for reference to morphology, if at all. As biochemical techniques
      begin to overcome the problems associated with ancient, degraded and formalin
      fixed tissues, the value of such collections increases. Molecular data are now
      available for rare, elusive and extinct species, as well as those densely sampled
      for epidemiological, biogeographical or clinical collections. Here, Elisabeth
      Herniou, Auriol Pearce and Tim Littlewood describe some of the advances and
      pitfalls associated with retrieving DNA from formalin-fixed helminth material and
      suggest just some of the new ways that parasitologists can tap into these
      resources.

PMID- 17040787
TI  - Erratum.

PMID- 17040788
TI  - Reply.

PMID- 17040789
TI  - More on malaria transmissibility.

PMID- 17040790
TI  - Malaria mortality: the pacific enigma-reply.

PMID- 17040791
TI  - Diagnosis of animal parasitism.

PMID- 17040793
TI  - Vector biology and the control of parasitic diseases.

PMID- 17040792
TI  - Global change and vector-borne diseases.

PMID- 17040794
TI  - The complete chromosomal organization of the reference strain of the Leishmania
      Genome Project, L. major ;Friedlin'.

PMID- 17040795
TI  - Cans of worms and cautionary tales on the web.

PMID- 17040796
TI  - From predicting mosquito habitat to malaria seasons using remotely sensed data:
      practice, problems and perspectives.
AB  - Remote sensing techniques are becoming increasingly important for identifying
      mosquito habitats, investigating malaria epidemiology and assisting malaria
      control. Here, Simon Hay, Bob Snow and David Rogers review the development of
      these techniques, from aerial photographic identification of mosquito larval
      habitats on the local scale through to the space-based survey of malaria risk
      over continental areas using increasingly sophisticated airborne and satellite
      sensor technology. They indicate that previous constraints to uptake are becoming
      less relevant and suggest how future delays in the use of remotely sensed data in
      malaria control might be avoided.

PMID- 17040797
TI  - Neuroinflammatory implications of Schistosoma mansoni infection: new information
      from the mouse model.
AB  - Schistosoma mansoni infection is known to induce granulomas, not only in the
      liver and intestine, but also in the brain, resulting in neuropathological and
      psychiatric disorders. In the past, the interaction between Schistosoma mansoni
      infection and the nervous system has received little attention. Here, Luigi Aloe
      and Marco Fiore discuss recent findings from experimental Schistosoma mansoni
      infection in the mouse nervous system showing that brain granulomas are
      associated with a significant alteration in the constitutive expression of nerve
      growth factor, a neurotrophic factor that plays an essential role in growth and
      differentiation and in preventing neuronal damage. These findings suggest that
      the neuropathological dysfunctions in neuroschistosomiasis may be linked to
      changes in the basal levels and/or activity of neurotrophic factors caused by
      local formation of granulomas.

PMID- 17040798
TI  - How does Trichinella spiralis make itself at home?
AB  - The nurse cell-parasite complex of Trichinella spiralis is unlike anything else
      in Nature. It is derived from a normal portion of striated skeletal muscle cell
      and develops in a matter of 15 to 20 days after the larva invades that cell type.
      What are the molecular mechanisms at work that result in this unique
      relationship? Here, Dickson Despommier presents a hypothesis to account for its
      formation, in which secreted tyvelosylated proteins of the larva play a central
      role. These proteins are always present in the intracellular niche of the larva
      from Day 7 after infection and may be responsible for redirecting host genomic
      expression, leading to nurse cell formation.

PMID- 17040799
TI  - Beyond strain typing and molecular epidemiology: integrated genetic epidemiology
      of infectious diseases.
AB  - In the past 20 years, genetic and molecular methods for characterizing pathogen
      strains have taken a major place in modern approaches to epidemiology of
      parasitic and other infectious diseases. Here, Michel Tibayrenc explains the main
      concepts used in this field of research, with special emphasis on the approaches
      developed in his team, and suggests future avenues to explore.

PMID- 17040800
TI  - The flip-side of Cytoadherence: immune selection, antigenic variation and the var
      Genes of Plasmodium falciparum.
AB  - In areas where Plasmodium falciparum is endemic, the natural immunity acquired by
      people exposed to frequent malaria infection is likely to have a differential
      selective impact upon different parasite genotypes. It has been suggested that
      the immune response directed against the variant antigen PfEMP1, which is
      expressed on the infected erythrocyte surface, is a crucial determinant of
      parasite population structure and favours the existence of distinct strains, or
      Varotypes. Here, Colin Sutherland summarizes current knowledge of the var
      multigene family, which encodes the PfEMP1 variants, and suggests that this
      information may allow certain predictions of the strain hypothesis to be tested
      directly.

PMID- 17040802
TI  - A different perspective on global mapping of lymphatic filariasis.

PMID- 17040801
TI  - Reply.

PMID- 17040803
TI  - Searching for a tree that can be trusted.

PMID- 17040804
TI  - A key to understanding Trypanosoma trees.

PMID- 17040805
TI  - Vertical food web interactions: evolutionary patterns and driving forces.
AB  - edited by K. Dettner, G. Bauer and W. Volkl, Ecological Studies Vol. 130,
      Springer-Verlag, 1997. pound76.00 (xxi+390 pages) ISBN 3 540 62561 5.

PMID- 17040806
TI  - Reply.

PMID- 17040807
TI  - Erratum.

PMID- 17040808
TI  - Advances in trematode biology.
AB  - edited by Bernard Fried and Thaddeus K. Graczyk, CRC Press, 1997. pound88.50 (466
      pages) ISBN 0 8493 2645 1.

PMID- 17040809
TI  - A broader view of malaria: from cell biology to health economics.

PMID- 17040810
TI  - Protozoan parasites: familiar faces, new directions.

PMID- 17040811
TI  - The Plasmodium falciparum Genome Project.

PMID- 17040812
TI  - Could british mosquitoes transmit falciparum malaria?

PMID- 17040813
TI  - What can bioinformatics do for parasitology research?

PMID- 17040814
TI  - Quality, quantity and function on the web.

PMID- 17040815
TI  - Iron acquisition by parasitic protozoa.
AB  - The efficient uptake of iron by microorganisms is essential for their survival.
      Mammalian hosts possess elaborate means of sequestering their iron stores to
      protect themselves against invading pathogens. In this review, Mary Wilson and
      Bradley Britigan summarize mechanisms by which bacteria and protozoa effectively
      scavenge iron from their hosts during infection, as well as the potential and
      proven effects of these mechanisms on microbial virulence.

PMID- 17040816
TI  - Natural human immunity to trypanosomes.
AB  - Complement-dependent destruction of invading micro-organisms is a crucial first
      line defense against infection, yet both African and American trypanosomes are
      able to resist attack by complement. African trypanosomes resist non-specific
      complement attack by virtue of a thick glycoprotein surface coat, and the host
      range of certain African trypanosomes is believed to be defined by their
      susceptibility to a subclass of human high density lipoprotein (HDL) and/or a
      high molecular weight protein complex present in human serum. In the first part
      of this review, Stephen Tomlinson and Jayne Raper look at the properties and
      mechanisms of action of these trypanolytic factors on African trypanosomes, and
      discuss briefly the possible mechanisms whereby these human pathogens resist
      lysis by human serum. The mechanisms that enable the American trypanosome
      Trypanosoma cruzi to resist complement attack are reviewed in the second part of
      this article.

PMID- 17040817
TI  - Costs and benefits of resistance against antimalarial drugs.
AB  - Recent experiments have suggested that resistance to antimalarial drugs, in
      particular chloroquine, is associated with increased transmission. However,
      epidemiological patterns suggest the opposite: ie. that resistance should be
      associated with a transmission cost. Here, Jacob Koella reviews the evidence for
      either a cost or a benefit of chloroquine resistance and proposes ideas from
      population and evolutionary biology that might explain the apparent contradiction
      between experimental and epidemiological evidence.

PMID- 17040818
TI  - Immunity to asexual blood stages of Plasmodium: is resistance to acute malaria
      adaptive or innate?
AB  - Current models of immunity to blood stages of Plasmodium invoke a primary role
      for T-cell dependent processes and much recent evidence implicates Th1-type
      responses as crucial to the control of acute malaria. But do these data stand up
      to close scrutiny? Here, Andy Fell and Nick Smith review recent data from rodent
      and human studies and suggest that Th1-type responses may not after all be
      important in controlling malaria infection in the blood.

PMID- 17040819
TI  - Malaria mortality rates in South Asia and in Africa: implications for malaria
      control.
AB  - Malaria mortality in human populations varies greatly under different
      circumstances. The intense malaria transmission conditions found in many parts of
      tropical Africa, the much lower malaria inoculation rates currently sustained in
      areas of southern Asia, and the epidemic outbreaks of malaria occasionally seen
      on both continents, present highly contrasting patterns of malaria-related
      mortality. Here Harsha Alles, Kamini Mendis and Richard Carter examine malaria
      related mortality under different circumstances and discuss implications for the
      management of malaria in these settings. They emphasize the power of rapid case
      treatment to save lives at risk under virtually all circumstances of malaria
      transmission.

PMID- 17040820
TI  - Lactate dehydrogenase and the diagnosis of malaria.
AB  - Over the past five years, several methods have been developed that exploit the
      differences between Plasmodium lactate dehydrogenase (pLDH) and the human LDH
      isoforms for the purposes of measuring pLDH in blood and in in vitro cultures.
      These methods have been incorporated into an easy screening method for the
      identification and quantitation of parasite growth in in vitro cultures using a
      Malstattrade mark reagent. In addition, another quantitative microplate method,
      the immunocapture pLDH (IcpLDH) assay, has been developed that utilizes
      monoclonal antibodies (mAbs) to capture the pLDH and then to measure the captured
      enzyme by its ability to reduce 3 acetyl pyridine adenine dinucleotide (APAD). In
      addition, a rapid immunochromatographic method, the OptiMAL(r) assay, has been
      formatted to capture pLDH as an antigen, and then to signal the presence of this
      captured antigen (enzyme) with a colloid conjugated antibody. The microplate
      IcpLDH assay, and the dipstick OptiMAL(r) assays, are both being used for the
      diagnosis and monitoring of malaria infections, as described here by Michael
      Makler, Rob Piper and Wil Milhous.

PMID- 17040821
TI  - Hypnozoites and malaria.

PMID- 17040822
TI  - Cerebral malaria and the induction of gametocytogenesis.

PMID- 17040823
TI  - Malaria CD-ROM.
AB  - Topics in International Health, Wellcome Trust, CAB International, 1998.
      pound45.00 (institutional), pound30.00 (student/individual), pound20.00 (some
      developing countries) ISBN 0 85199 2439.

PMID- 17040824
TI  - Schistosomiasis: forty years' war on the worm.
AB  - Schistosome vaccine candidates are now entering phase I clinical trials. In an
      attempt to illustrate the progress made towards control, and the definition of
      potential vaccines against schistosomiasis, Andre Capron reviews some of the
      major findings and observations that have led to a significant evolution of our
      concepts, together with the production of novel and promising tools. It is
      obvious that our most important advances have proceeded from the successful
      integration of convergent knowledge in biology, epidemiology and biotechnology.
      At this stage, nobody can predict what will be the outcome of the current trials,
      but an important step has certainly been made towards immunointervention in human
      schistosomiasis.

PMID- 17040825
TI  - Morbidity in schistosomiasis: assessment, mechanisms and control.

PMID- 17040826
TI  - An international initiative on praziquantel use.

PMID- 17040827
TI  - Schistosomiasis research: the end of the beginning.

PMID- 17040828
TI  - Schistosome and nematode ancestry on the web.

PMID- 17040829
TI  - Schistosomes: unanswered questions on the basic biology of the host-parasite
      relationship.
AB  - As is the case in many parasite infections, research into schistosomiasis has not
      yet yielded a vaccine and, although chemotherapy with praziquantel is very
      effective, the mechanism of action of this drug is unknown. John Kusel and
      colleagues here suggest that an understanding of basic biological phenomena, such
      as the role of Ca(2+) in skin penetration and the function of the adult excretory
      system, might lead to important breakthroughs. Other crucial questions are also
      addressed, with the hope of stimulating debate. They invite suggestions and
      correspondence from others working in related fields.

PMID- 17040830
TI  - Glucose Transport and Metabolism in Mammalian-stage Schistosomes.
AB  - Adult schistosomes transport nutrients from the host bloodstream across their
      outer body covering or tegument. The tegument is a cytologically unusual
      structure; it is a syncytium bounded externally by two lipid bilayer membranes.
      In this review, Patrick Skelly, Louis Tielens and Chuck Shoemaker reconsider our
      understanding of how glucose enters schistosomes across this unusual outer
      covering in the light of recent papers characterizing glucose transport proteins
      and glucose metabolism pathways in these parasites.

PMID- 17040831
TI  - Schistosome immunology: more questions than answers.
AB  - The past 30 years have seen research on the immunology of schistosomiasis move to
      encompass studies of responses in naturally exposed human populations, in
      addition to the studies in animal model systems. While animal systems still
      retain an important place in research on the immunology of schistosomiasis,
      recent debate has centred on aspects of human immunological responses that may or
      may not be associated with resistance or susceptibility to infection. In this
      article, Paul Hagan, Patricia Ndhlovu and David Dunne take stock of the present
      state of knowledge and offer their views on prospects for the future.

PMID- 17040832
TI  - Snail control strategies for reduction of schistosomiasis transmission.
AB  - As intermediate hosts, molluscs play a major role in the transmission of
      schistosomes; they are the sites of an intense multiplication of parasites. Thus,
      snail control strategies are considered a priority for the reduction of
      schistosomiasis transmission. Here, Vinca Lardans and Colette Dissous review the
      efficacy of environmental management and the use of molluscicides and biological
      agents to control snail populations. They then describe the development of
      diagnostic tests, based on the detection of parasite antigens or specific
      parasite DNA sequences in snail tissues, to detect the early infection of snails.
      Finally, they discuss progress in studying the molecular basis of susceptibility
      and resistance phenotypes, and the possible application of the genetic
      manipulation of molluscs.

PMID- 17040833
TI  - Chemotherapy of schistosomiasis: an update.
AB  - No major changes have occurred during the past 20 years regarding the therapeutic
      tools available to the clinician for the treatment of schistosomiasis. If
      anything, the two drugs (oxamniquine and metrifonate) that are valuable
      alternatives to the drug of choice (praziquantel) have become more difficult to
      procure in some African countries. Here, Donato Cioli summarizes some of the most
      recent and interesting laboratory studies on potential antischistosomal
      compounds, and then reviews recent developments related to the mechanism of
      action of praziquantel and to the possible emergence of praziquantel-resistant
      schistosomes.

PMID- 17040834
TI  - Cytokine Interaction and Immune Responses during Schistosoma mansoni Infection.
AB  - Of the estimated 200 million people infected with Schistosoma, a subset develop
      severe life-threatening disease. Adult Schistosoma mansoni are refractory to the
      immune response and are long-lived, causing chronic exposure to parasite antigen.
      Although the adult worms themselves are not antigenically inert, it is the
      parasite eggs that, by accumulating in the liver and traversing the intestinal
      wall, place a complex series of often-conflicting demands on the host's immune
      system. In this article, Laura Rosa Brunet, David Dunne and Edward Pearce discuss
      data from experimental studies in the mouse and field studies in endemic areas
      that combine to suggest that it is a failure to juggle this immunological
      conflict that results in severe disease.

PMID- 17040835
TI  - Patterns in parasite epidemiology: the peak shift.
AB  - A characteristic relationship between infection and host age, with levels of
      infection reaching a peak in particular age classes, has been reported for many
      parasites. However, several field studies have shown that this relationship is
      not invariant: if age-infection data are compared across host populations, the
      peak level of infection is higher and occurs at a younger age when the
      transmission rate is high, and is lower and occurs at an older age when it is
      low. This pattern is called the ;peak shift'. Here, Mark Woolhouse reviews the
      evidence for and the implications of the peak shift. The peak shift is consistent
      with the predictions of mathematical models that assume gradually acquired
      protective immunity, and this interpretation is supported by experimental studies
      using animals. This agreement between theory, experimental evidence and field
      studies strongly suggests that acquired immunity has a major impact on
      epidemiological patterns not only for parasites such as malaria, where the
      importance of acquired immunity is not in doubt, but also for many parasitic
      helminths, where the role of acquired immunity is less widely accepted.

PMID- 17040836
TI  - Is Schistosomicidal Chemotherapy Sub-curative? Implications for Drug Resistance.

PMID- 17040837
TI  - Puberty and Age-intensity Profiles in Schistosome Infections: Another Hypothesis.

PMID- 17040838
TI  - More on the search for a schistosomiasis vaccine.

PMID- 17040839
TI  - Reply.

PMID- 17040840
TI  - Kinetoplast DNA minicircle database.

PMID- 17040841
TI  - Epidemiology and control of bovine theileriasis.

PMID- 17040842
TI  - The liverpool school of tropical medicine: 100 years of parasitological
      achievement.

PMID- 17040843
TI  - Spirochetes, ticks and DNA.

PMID- 17040844
TI  - Words and language on the web.

PMID- 17040845
TI  - The molecular mechanisms of giardia encystation.
AB  - The protozoan parasite Giardia lamblia is transmitted as an environmentally
      resistant cyst. The encystation process is attracting attention not only from the
      viewpoint of disease transmission, but also as a model for differentiation. Here,
      Hugo Lujan, Michael Mowatt and Theodore Nash discuss molecular events underlying
      this process, including the induction of expression and transport of cyst wall
      proteins and the induction of Golgi-like activity. They also propose that the
      signal for encystation derives from cholesterol deprivation in the lower small
      intestine.

PMID- 17040846
TI  - Genetic basis of trypanotolerance in cattle and mice.
AB  - Under most circumstances, certain breeds of domestic ruminants show a remarkable
      resistance to the effects of African trypanosomiasis: they can tolerate the
      presence of parasites while apparently controlling levels of parasitaemia and,
      crucially, not showing the severe anaemia and production loss that are
      characteristic of infection in susceptible hosts. As discussed here by Stephen
      Kemp and Alan Teale, the genetic control of this phenomenon might finally be
      yielding to gene mapping studies. Genetic regions determining susceptibility to
      trypanosomiasis in mice have been identified and parallel studies are well
      advanced in cattle. There is growing evidence that only modest numbers of genes
      are involved in determining the difference between a susceptible and a resistant
      animal. These observations raise a new series of important questions concerning
      the possible exploitation of major trypanotolerance genes and the way that they
      might function in different genetic and physical environments.

PMID- 17040847
TI  - Hypodermin a and inhibition of lymphocyte proliferation.
AB  - Infection with Hypoderma lineatum is accompanied by modulation of the host's
      immune system. Here, Nathalie Moire describes some in vitro studies examining how
      the parasitic enzyme hypodermin A interferes with lymphocyte proliferation.

PMID- 17040848
TI  - Geographic Information Systems and the Selection of Priority Areas for Control of
      Tsetse-transmitted Trypanosomiasis in Africa.
AB  - In this paper, Tim Robinson describes the use of geographic information systems
      (GIS) to prioritize areas for tsetse and trypanosomiasis control in Zambia.
      Digital maps of land tenure, percentage agriculture, stocking rates and relative
      arable potential are combined within a GIS to identify areas where
      trypanosomiasis is a direct constraint to agricultural development and where the
      presence of tsetse prevents access to areas adjacent to those under high pressure
      from livestock and agriculture. The techniques described in this paper could be
      applied to a range of livestock diseases in many parts of the world.

PMID- 17040849
TI  - The use of PCR genotyping in the assessment of recrudescence or reinfection after
      antimalarial drug treatment.
AB  - In the past, assessment of drug efficacy against Plasmodium falciparum malaria
      has been performed by microscopy, screening for parasites in blood smears.
      However, in areas of high endemicity, reappearing parasites might be derived from
      new inoculations and could be classified falsely as treatment failures. Recently,
      a number of studies have used polymerase chain reaction (PCR) analysis of
      detectable parasites after drug administration to discriminate new infections
      from true recrudescence. The feasibility, high sensitivity and high resolution of
      this technique proves that it will be practical and highly valuable in studies on
      both drug resistance and vaccine efficacy as well as the testing of novel
      antimalarial drugs. In this article, Georges Snounou and Hans-Peter Beck discuss
      the uncertainties in the interpretation of data inherent to the technical
      limitations of the PCR technique, and the constraints imposed by the biology of
      the parasite. They suggest that although genotyping can provide strong evidence
      for differentiating between true recrudescence and reinfection, it must be
      interpreted with caution. They also propose strategies that might help minimize
      these uncertainties.

PMID- 17040850
TI  - Reply.

PMID- 17040851
TI  - Multiparasitism in sub-saharan west african countries: don't forget the least
      important!

PMID- 17040852
TI  - The eradication of infectious diseases.
AB  - edited by W.R. Dowdle and D.R. Hopkins, Wiley, 1998. pound60.00 (hbk) (xv +218
      pages) ISBN 0 471 98089 7.

PMID- 17040853
TI  - PCR detection of cryptosporidium-addendum.

PMID- 17040855
TI  - Sixty years of culture.

PMID- 17040854
TI  - Vector control: methods for use by individuals and communities.
AB  - by Jan A. Rozendaal, World Health Organization, 1997. pound85.00 (xii +412 pages)
      ISBN 92 4 154494 5.

PMID- 17040856
TI  - Onchocerciasis: The First Decade of Mectizantrade mark Treatment.

PMID- 17040857
TI  - Viability of nematode larvae after exsheathment with sodium hypochlorite.

PMID- 17040859
TI  - Questions and answers on the web.

PMID- 17040858
TI  - The Case for Naming Actinosporeans using the Zoological Code.

PMID- 17040860
TI  - The Thrombospondin-related Protein Family of Apicomplexan Parasites: The Gears of
      the Cell Invasion Machinery.
AB  - A number of severe diseases of medical and veterinary importance are caused by
      parasites of the phylum Apicomplexa. These parasites invade host cells using
      similar subcellular structures, organelles and molecular species. Proteins
      containing one or more copies of the type I repeat of human platelet
      thrombospondin (TSP1), are crucial components of both locomotion and invasion
      machinery. Members of this family have been identified in Eimeria tenella, E.
      maxima, Toxoplasma gondii, Cryptosporidium parvum and in all Plasmodium species
      so far analysed. Here, Andrea Crisanti and colleagues discuss the structure,
      localization and current understanding of the function of TSP family members in
      the invasion of target cells by apicomplexan parasites.

PMID- 17040861
TI  - Environmental assessment of larvicide use in the onchocerciasis control
      programme.
AB  - The objective of the Onchocerciasis Control Programme (OCP) is to eliminate
      onchocerciasis as a disease of public importance and as an obstacle to socio
      economic development. The OCP was initially based solely on the control of the
      blackfly vector, Simulium damnosum sensu lato, by insecticide spraying of the
      breeding sites on river systems, where larval stages develop. Results of
      monitoring the environmental effects and the process of risk assessment for new
      insecticides are reviewed. The achievements of this strategy are outlined here by
      Davide Calamari, Laurent Yameogo, Jean-Marc Hougard and Christian Leveque.

PMID- 17040862
TI  - Molecular Biology's Lessons about Toxoplasma Development: Stage-specific
      Homologs.
AB  - Within intermediate hosts (such as humans), the protozoan parasite Toxoplasma
      gondii has two life cycle stages: a rapidly replicating form called a tachyzoite
      and a slowly growing, quiescent form called a bradyzoite. Recently, molecular
      biology studies have shown that tachyzoites and bradyzoites express a number of
      homologs (ie. evolutionary related genes)expressed exclusively in one or the
      other stage. Here, Laura Knoll and John Boothroyd describe examples of how these
      stage-specific homologs were discovered, and speculate about their regulation and
      functional significance.

PMID- 17040863
TI  - The Search for Novel Malaria Transmission-blocking Targets in the Mosquito
      Midgut.
AB  - The need for new malaria control strategies has led to increased efforts to
      understand more clearly the mosquito stages of Plasmodium. The absolute
      requirement of gamete maturation and fertilization, transformation of sedentary
      zygote to motile ookinete, ookinete interaction and invasion of gut epithelium,
      and the survival of the mosquito against immune attack suggest that numerous
      unidentified targets exist, which could be modified to achieve transmission
      blocking of malaria. In the search for new transmission-blocking targets in the
      mosquito gut, Mohammed Shahabuddin, Stephane Cociancich and Helge Zieler here
      summarize recent studies to identify the cellular and biochemical factors that
      affect the malaria parasite's development; in particular, factors influencing the
      early development of Plasmodium, receptor-mediated interactions between the
      parasite and the mosquito midgut, and the gut-associated immune responses
      directed against Plasmodium.

PMID- 17040865
TI  - Waterborne cryptosporidiosis and the need for legislation.

PMID- 17040864
TI  - The application of attributable risk analysis in helminth epidemiology.
AB  - Estimating the public health impact of endemic helminth infections is an
      important component of control strategies that aim not only to reduce the number
      of infections in a community, but also to improve community health. This is not
      straightforward, as the risk of morbidity in an infected individual can be
      influenced by a number of factors, and different infections can cause similar
      symptoms. Here, Mark Booth describes how attributable risk analysis techniques
      based on 232 tables can be used to address these problems, and how they were
      applied to estimate the public health impact of Schistosoma japonicum infections
      in three villages in China.

PMID- 17040866
TI  - Reply.

PMID- 17040867
TI  - Parasitism and the platyhelminthes.
AB  - by Graeme C. Kearn, Chapman & Hall, 1998. pound115.00 (xii +544 pages) ISBN 0 412
      80460 3.

PMID- 17040868
TI  - Infection, oxford general practice series 40.
AB  - edited by L. Southgate, C. Lockie, S. Heard and M. Wood, Oxford University Press,
      1997. pound27.50 (476 pages) ISBN 0 919 262092 4.

PMID- 17040869
TI  - Nitric oxide in health and disease.
AB  - by Jill Lincoln, Charles H.V. Hoyle and Geoffrey Burnstock, Cambridge University
      Press, 1997. pound24.95 (pbk)/ pound70.00 (hbk) (xiv +363 pages) ISBN 0 521 55977
      4/0 521 55038 6.

PMID- 17040870
TI  - Immune effector mechanisms in parasitic infections.
AB  - edited by F.Y. Liew and K. Vickerman, Philosophical Transactions of the Royal
      Society of London Series B, Vol. 352, No. 1359, 1997. pp 1293-1394, ISSN 0962
      8436.

PMID- 17040871
TI  - [Serologic diagnosis of chlamydial and Mycoplasma pneumoniae infections].
AB  - The diagnosis of Chlamydia trachomatis infection can be based either on direct
      detection of the organism or its components or indirectly by measuring antibodies
      as markers of the individual's response to the infection. The latter is currently
      of limited value. Neither IgG or IgA antibodies can be used to diagnose current
      genital infection by Chlamydia trachomatis or to exclude such an infection. There
      is no solid ground as yet for the use of IgA antibodies as a marker of persistant
      or unresolved infection. Commercial tests in the Elisa format based on peptides
      from the MOMP of Chlamydia trachomatis are available and show good specificities
      and sensitivities. Hsp60 seems to have a unique role in the development of tubal
      scarring and antibodies to chsp60 could predict tubal factor infertility.
      Serology is the main diagnostic tool for the diagnosis of Mycoplasma pneumoniae
      infection. The serologic assays are the complement fixation test (CF),
      immunofluorescence, the microparticle agglutination and recently EIAs. The CF
      test is still used for serodiagnosis of Mycoplasma pneumoniae infection because
      of the sensitivity of 90%. Single titer of >or= 64 are considered to be
      indicative of recent infection. A number of commercial EIAs have been developped.
      The difficulty for IgG interpretation is a definition of a cutoff value for
      discriminating infected and healthy subjects. Most of the IgM assays show good
      diagnostic sensitivities and are valuable tools for the early diagnosis of
      Mycoplasma pneumoniae infection in children. There are no wholly satisfactory
      serological methods for diagnosis of Chlamydia pneumoniae infection. Problems
      arise from the high background of IgG antibody prevalence, the lack of
      standardized testing methods.

PMID- 17040872
TI  - [Primary immunodeficiencies and Bruton's disease genetic analysis: which
      prospects offers this genetic diagnosis?].
AB  - Bruton's disease is the most frequently primary X-linked immunodeficiency.
      Bruton's tyrosine kinase (Btk) is encoded by the XLA gene that when mutated
      causes bruton's disease. This protein acts in multiple intracellular signaling
      pathways where the BCR (B-cell receptor) pathway is the most elucidated. Moreover
      400 mutations were found and identified as responsible for B-cells
      differentiation block; consequences are a lack of B-cells in peripheral blood and
      hypo/agammaglobulinemia. Thus, patients are more susceptible to early and
      recurring infections occurring before the age of one year. Laboratory testing
      allow differential diagnosis among primary immunodeficiencies in which others
      hypogammaglobulinemia. Genetic analyses help physicians for clinical and
      biological diagnosis, and allow prenatal diagnosis for patient's family.
      Patient's management is based upon polyclonal immunoglobulin supplementation,
      infectious diseases prevention and genetic advice.

PMID- 17040873
TI  - [Functional characterization of naturally occurring CFTR mutants: interest for
      cystic fibrosis].
AB  - Cystic fibrosis is caused by mutations in the CFTR gene (Cystic Fibrosis
      Transmembrane conductance Regulator) encodes a protein mainly functioning as a
      chloride channel that regulates chloride and sodium transport in secretory
      epithelial cells. The past several years with advances in DNA analysis have seen
      an increased knowledge of the mutational spectrum for cystic fibrosis. The
      functional characterization of some naturally occurring CFTR mutants led to
      classification of mutations according to the mechanisms by which they disrupt
      CFTR function. This article reports the strategies that are currently available
      to evaluate the deleterious consequences of naturally occurring CFTR mutants. A
      number of in silico tools and molecular approaches are presented. The accurate
      knowledge of CFTR mutations causing or non-causing disease present obvious
      interest in both clinical diagnosis and research fields. A better understanding
      of the molecular defects associated with various CFTR mutations will provide a
      basis for development of novel pharmacologic compounds intended to correct
      transcriptional abnormalities or improve protein processing/trafficking. This is
      illustrated by the functional characterization of the first sequence variation
      identified in the CFTR minimal promoter, which allowed to address in original way
      the important and poorly understood regulation of expression of the CFTR gene.

PMID- 17040874
TI  - [Prevalence of celiac disease serological markers in Tunisian type 1 diabetic
      adults].
AB  - OBJECTIVE: to evaluate the prevalence of celiac serological markers; anti
      transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti
      reticulin (AR) antibodies; in type 1 diabetic Tunisian adults. SUBJECTS AND
      METHODS: 261 type 1 diabetic patients aged from 16 to 60 years were enrolled in
      this prospective study. IgG and IgA transglutaminase and gliadin were measured
      with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates;
      monkey oesophagus and human umbilical cord. AR were detected by indirect
      immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured
      by turbidimetry. RESULTS: 83/261 of diabetics were positive for at least one
      antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical
      cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance
      between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency
      and one of them has IgG AE and ATGt. CONCLUSION: serological markers of celiac
      disease seem to be frequent in diabetics. Nevertheless, diagnosis must be
      confirmed by histological studies which allow us to know the real prevalence of
      celiac disease in diabetic adults.

PMID- 17040875
TI  - [Validation of a Bruton's disease genetic analysis method].
AB  - Bruton's disease is the most frequently primary X-linked immunodeficiency.
      Patients are more susceptible to early and recurring infections associated with
      hypo/agammaglobulinemia and a severe B-cell deficiency. Moreover, 400 mutations
      were found in the XLA gene which codes the Btk tyrosine kinase and were
      identified as responsible for Bruton's disease. Genetic study was carried out
      with one group of patients named NECKER, composed by five XLA patients and two
      parents whose XLA gene was sequenced by an Italian crew. Results were obtained by
      PCR of 19 exons and initial/terminal intron's parts, followed by PCR-sequencing
      with universal primers and sequencing. The results from this study allowed the
      validation of the sequencing technique by comparing NECKER group data (equivalent
      results with Italian data). In addition, the mutation multiplicity (described or
      not, coding/non coding) need an exact analysis that should be given to clinicians
      through clear and trustful results. In this way, a strategy to analyse untreated
      results was created based on the mutation type. The genetic analysis could help
      physicians for uncertain diagnosis in immune defficiencies, allows proposing a
      genetic advice to the patient's family and the construction of a data base
      permits a best understanding of this disease.

PMID- 17040876
TI  - [Significance of "anti HBC alone" serological profile in 284 patients suspicious
      of being infected with hepatitis B virus].
AB  - The "anti-HBc alone" serological profile is a frequent finding in hepatitis B
      virus infections, but little is known about its clinical significance. The aim of
      this study was to explore the 'anti-HBc alone' serological profile obtained by
      immunosorbent assay (ELISA) in 284 patients suspicious of being infected with
      hepatitis B virus. Sera were screened for following serological markers: HBs Ag,
      anti-HBc and anti-HBs antibodies using immunoradiometric assay (IRMA) and for HBV
      DNA using polymerase chain reaction. Among 284 studied sera with 'anti-HBc alone'
      serological profile, 124 were positives for anti-HBs antibodies by IRMA and
      corresponding to a recovered form of hepatitis B. Nineteen sera were negatives
      for anti-HBc antibodies, suggesting false positive results by ELISA. Two sera
      were found positives for HBs Ag by IRMA, which are related to authentic hepatitis
      B. HBV DNA was positive in 4 sera, suggesting occult hepatitis B. This study
      indicates that "anti-HBc alone" serological profile is most often correlates with
      recovered hepatitis B infection, but it can mask an occult hepatitis B.

PMID- 17040877
TI  - [Haematological characteristics, FAB and WHO classification of 153 cases of
      myeloid acute leukaemia in Tunisia].
AB  - A complete blood analysis with a careful morphologic examination of peripheral
      blood and bone morrow smears completed by cytochemical reaction will help to
      classify the most acute myeloid leukaemia (AML). Actually, the study of other
      cytogenetis and immunophenotypic markers are now necessary to confirm diagnosis.
      The World Health Organisation WHO classification (2001) incorporates theses
      approaches. The purpose of this study is a bio-clinical review according to the
      WHO recommendations in 153 cases of LAM diagnosed between January 1998 and
      December 2003. The patients were aged 2 months to 90 years with sex ratio (M/F)
      of 1,22. The morphologic conclusion was difficult in 12% cases. Presence of
      dysplasia is noted in 50% of cases with multilineage dysplasia in 42% of cases.
      Our results showed cloned chromosomal abnormalities in 57% of cases (t(8;21):
      12%, t(15;17) : 10%, Inv16: 1,3%, 11q23: 2,6% et complex karyotype: 14,3%). In
      69% of cases with multilineage dysplasia, the karyotype was normal. 3 cases of
      LAM were noted at patients treated for breast cancer with chirurgic chemotherapy
      and radiotherapy 3, 4 et 5 years after treatment (LAM3 with t(15;17), LAM4 with
      genetic abnormalities of chromosomes 3, 5, 7, 8, 9, 14 et 16 et LAM 6 with
      genetic abnormalities of chromosomes 4, 7, 12, 14, 19 et 21). In WHO
      classification, cytology is essential in diagnosis of LAM even if the karytype
      have an important prognostic value. Research of signs of dysplasia lineage after
      lineage constitutes an important microscopic work and it is difficult to quantify
      dysplasia when the lineage is poor.

PMID- 17040878
TI  - [Simultaneous detection of IgM anti-Epstein-Barr virus and IgM anti-hepatitis A
      during an acute hepatitis].
AB  - We report a case of a 15-year-old young man who was admitted for an acute
      hepatitis. Virological assessment showed both IgM anti-EBV and IgM anti-hepatitis
      A. IgG anti-EBNA and clinical history allowed to rule out the hypothesis of a
      recent EBV infection and confirmed the diagnosis of acute hepatitis A infection.

PMID- 17040879
TI  - [Adaptation of methotrexate determination in plasma with Dimension Xpand].
AB  - The treatment with methotrexate at high doses is responsible of many side
      effects. It's necessary to evaluate serum methotrexate rate to monitor the
      administration of the methotrexate antagonist, the folinic acid. The aim of this
      study is to validate the determination of methotrexate in plasma using the
      automate Xpand Dimension (Dade Behring). Assay results were linearly related to
      the concentration for the wide range which was examinated (0.15 - 1.4
      micromol/L). We report the precision, accuracy, linearity, sensitivity of this
      assay. The CV was less than 10%. We present the results of correlations with Aca
      (Dade Behring) and Cobas Mira (Roche). The reagent cartridge in the instrument
      and the calibration are stable during 28 days.

PMID- 17040880
TI  - [Non-secreting myeloma associated with nephrotic syndrome].
AB  - The non-secreting myeloma is a rare form of myeloma. Its association with a
      nephrotic syndrome is exceptional. The observation which we report below
      described the history of a 66 years old patient who presents a non-secreting
      myeloma revealed by a nephrotic syndrome. Various assumptions on the mechanism of
      no excretion were put forth. Nevertheless, several points are to be elucidated as
      for the pathogenesis of the association non-secreting myeloma and nephrotic
      syndrome.

PMID- 17040881
TI  - [Hyperhomocysteinaemia and type 2 diabetes].
AB  - OBJECTIVES: Hyperhomocysteinaemia is associated with cardiovascular events in
      nondiabetic individuals. The present study was aimed to explore the implication
      of hyperhomocysteinemia in development of cardiovascular events in patients with
      type 2 diabetes. DESIGN: A total of 185 patients with type 2 diabetes (115 women
      and 70 men, 30 to 93 years of age) have been included consecutively in the
      ambulatory unit at the Saint-Philibert Hospital. For each patient the
      concentration of homocysteine, cholesterol and triglyceride levels and HbA1c have
      been measured. In the studied population, 121 patients presented cardiovascular
      events (myocardial infarctus, peripheric arteriopathy, cerebrovascular accident).
      RESULTS: The patients with cardiovascular events were older, the concentration of
      homocysteine and creatinine were higher. The plasma homocysteine levels adjusted
      for age and creatinine levels were higher in patients with cardiovascular events
      than in patients without cardiovascular events (15.4 +/- 3.52 micromol/L and
      13.13 +/- 2.26 micromol/L respectively; p = 2. 10(-5)). CONCLUSIONS:
      Hyperhomocysteinemia is an independant risk factor for cardiovascular events in
      type 2 diabetes, independent of age and renal function.

PMID- 17040882
TI  - [Incubated osmotic fragility test does not exclude red blood cell membrane
      disorders! About a case of hereditary elliptocytosis].
AB  - We report a case of hereditary elliptocytosis in an infant diagnosed a few months
      after the birth, in a context of regenerative normocytic normochromic anaemia.
      The investigations, including incubated osmotic fragility, erythrocytic enzymes
      study and haemoglobin electrophoresis, were not contributive. Only the
      persistence of elongated (or cigar-shaped) erythrocytes on blood smears was
      noted. Hereditary elliptocytosis was confirmed by specialized investigations
      (rheological study and erythrocytic membrane proteins electrophoresis).
      Investigations in the mother were realized and led to the discovery of a similar
      biological pattern. Hereditary elliptocytosis is a red blood cell membrane
      disorder due to the defect in cytoskeleton proteins (spectrin or 4.1), leading to
      the loss of deformability properties of erythrocytes. This disorder is considered
      as rare; however, its incidence is probably underestimated because most cases are
      pauci- or asymptomatic and the discovery is often fortuitous. The absence of
      detection of this defect by incubated osmotic fragility should not discard the
      hypothesis of erythrocytes membrane disorders. The persistent observation of
      elongated erythrocytes on blood smear must encourage the biologist to evocate a
      hereditary elliptocytosis.

PMID- 17040883
TI  - [Acute polyarthritis during a parvovirus B19 primary infection].
AB  - Parvovirus B19 classically causes erythema infectiosum in children, febrile
      arthralgia or acute erythroblastopenia in adult. The clinical spectrum of adult
      primary infection is sometimes misleading. We report an observation of an acute
      rheumatoid-like arthritis following primary parvovirus B19 infection in a 42-year
      old woman.

PMID- 17040884
TI  - [Severe imported malaria. The experience of the military hospital of Marrakech].
AB  - Incidence of severe imported malaria increases with the multiplication of
      humanitarian and military missions in malarial endemic areas. The purpose of this
      study was to describe the demographic, clinical, therapeutic and outcome aspects
      of 9 cases which have been hospitalized in the intensive care unit and medecine
      service of the military hospital of Marrakech, between january 2001 and december
      2004. Out of 68 patients admitted with symptomatic malaria during this period, 9
      cases were considered as severe. All of them were male soldiers (mean age: 33,3
      years), 7 of them have stayed in Democratic Republic of Congo, and 2 in Ivory
      Coast. Chemoprophylaxis consisted in chloroquine plus proguanil in 5 cases and
      mefloquine in 4 cases. The mean duration of stay in endemic area was 9,3 months.
      The clinical presentation was dominated by troubles of consciousness, which
      justified initial admission in the intensive care unit. The mean duration of
      hospitalization was 3,3 days in intensive care unit and 5,6 days in the medical
      department. Thick smear always revealed high parasitemia (5-15%) with Plasmodium
      falciparum, associated with Plasmodium ovale in two cases. Antimalarial treatment
      consisted in quinine salts administration. Evolution was favourable without
      recurrence in 7 cases, but 2 deaths were recorded. Severe imported malaria
      remains associated with bad outcome and requires early diagnosis and close
      monitoring of such cases.

PMID- 17040885
TI  - [National external quality assessment in auto-immunity: auto-antibodies against
      thyroid constituents].
AB  - The French Health Products Safety Agency organized in 2005, for the scheme of the
      national external quality assessment, a survey on antibodies against thyroid
      constituents which included for the first time the quantitative assay. The
      purpose of this survey was to assess the quality of the different methods of
      these assays. The overall qualitative results are satisfactory. However, this
      survey pointed out a lower performance for immunodot which appeared to have been
      misused. Concerning the titer of antibodies, results show a broad dispersion
      between reagents. This confirms the lack of a real standardisation despite of the
      existence of the international MRC standards.

PMID- 17040886
TI  - Does low mercury containing skin-lightening cream (fair & lovely) affect the
      kidney, liver, and brain of female mice?
AB  - Fair & Lovely is an over-the-counter skin-lightening cream sold widely in Saudi
      markets. Its mercury content is 0.304+/-0.316 microg/g, in the range of 0.102 to
      0.775 microg/g. This study was designed to evaluate its toxic effects on mice.
      The cream was applied on mice for a period of 1 month at different intervals.
      Mercury levels were measured in the liver, kidney, and brain tissue samples of a
      total of 75 adult female CD1 mice by Atomic Absorption Spectrophotometer coupled
      to a Vapor Generator Accessory. The mean mercury concentrations in the tissues of
      the treated mice were 0.193+/-0.319 microg/g; whereas for the control group, it
      was 0.041 microg/g+/-0.041microg/g. While the kidney was found to have the
      highest mercury content, the brain was found to have the lowest content. Treated
      mice showed a significant reduction in body weight. Marked histological changes
      were clearly noted in the kidney and, to a lesser extent, in the brain and liver.
      These results indicate that although Fair & Lovely mercury content is less than
      the U.S. Food and Drug Administration (FDA) permissible limits histopathological
      changes in the brain, kidney, and liver tissues are evidence of its possible
      toxicity.

PMID- 17040887
TI  - Correlating sensory effects with irritation.
AB  - The goal of this preliminary study was to examine data collected in the course of
      the development and conduct of the behind-the-knee (BTK) test for correlations
      between the objective scores of erythema and the sensory effects reported by the
      panelists. In addition, the intensity of physical characteristics of femcare
      products and prototypes was evaluated using the descriptive analysis panel (DAP)
      and results were compared to the BTK results to determine if certain physical
      characteristics of the products correlated to different sensations experienced by
      the BTK panelists. Test materials were commercially available or developmental
      catemenial products. In the BTK test, samples were applied daily to the area
      behind the knee and held in place for 6 hours per day for 5 consecutive days by
      an elastic knee band of the appropriate size. Irritation was graded 30-60 minutes
      after removal of each application. The DAP uses individuals trained to recognize
      and grade certain physical characteristics of products, including degree of
      plastic feel, scratchiness, glide, and cottony feel. In the BTK studies, the
      ability to differentiate between the test samples via reported sensory effects
      correlated with the ability to differentiate via objective scores for irritation
      in seven of 15 comparisons. A correlation between the magnitude of the irritation
      score, independent of the specific test sample, and reports of adverse sensory
      effects was observed in 13 of 15 comparisons. Two comparisons conducted in the
      BTK were also evaluated using the DAP. For one comparison, there was a clear
      difference in the product physical characteristics in the DAP that was consistent
      with mean erythema scores and reported sensory effects in the BTK. For the other
      comparison, there was no clear difference between the two products by either the
      DAP or the BTK.

PMID- 17040888
TI  - Comparative cytotoxicity potential of soft contact lens care products.
AB  - PURPOSE: To determine the cytotoxicity potential of soft contact lens care
      products and benzalkonium chloride (BAK) by two colorimetric in vitro assays on
      an immortalized human corneal epithelial cell line (HCE-T). METHODS: Four
      commercial soft contact lens care solutions were tested at 1:3 dilution in growth
      medium. The positive controls for cytotoxicity were BAK in Dulbecco's phosphate
      buffered saline (DPBS) at 10, 5, 2.5, and 1.25 ppm and 1:3 dilution of DPBS as
      negative control. Cell viability was assayed using a novel tetrazolium compound
      and an electron coupling reagent (MTS/PES), and by cell membrane integrity using
      neutral red dye uptake and release (NRUR). Mean spectrophotometric optical
      density of the test samples was compared to mean optical density of the controls
      at 24 and 48 hours of exposure to test product. Significance was measured by
      ANOVA/Tukey HSD test. RESULTS: Cell viability and cell membrane integrity tests
      were not significantly different between lens care solutions and the negative
      controls for CIBA Vision SOLOcare PLUS, Advanced Medical Optics COMPLETE Comfort
      PLUS, or BAK at 1.25 ppm. Exposure to Bausch and Lomb ReNu MultiPlus, Alcon OPTI
      FREE Express with Aldox, BAK 10, 5, and 2.5 ppm yielded significant reduction in
      cell viability and membrane integrity compared to negative controls. DISCUSSION:
      Assays of HCE-T cell viability by MTS/PES, and cell membrane integrity by NRUR
      cells yielded data that were similar to that previously reported with mouse L929
      cells in tests based on the USP Elution Test. For the MTS/PES and NRUR assay
      methods, the solutions in order of increasing cytotoxicity potential were:
      SOLOCare = COMPLETE Comfort Plus < ReNu < < OPTI-FREE Express with Aldox.

PMID- 17040889
TI  - Preparation and characterization of demeclocycline liposomal formulations and
      assessment of their intraocular pressure-lowering effects.
AB  - The objective of the present study is to enhance the ocular permeability and to
      study the ocular disposition of demeclocycline (DEM), liposomal topical
      formulation for treatment of elevated intraocular pressure using Male New Zealand
      albino rabbits as an animal model. METHODS: Different liposomal formulations of
      the DEM were prepared and characterized for their drug entrapment, drug-liposome
      affinity and the in vivo distribution of DEM in various ocular tissues. Liposomal
      formulations of promising drug distribution within the various ocular tissues
      have been scaled up for the in vivo intraocular pressure (IOP) measurements by
      Pneuma-tonometer using different dosing regimens. RESULTS: The amounts of drug
      entrapped in the charged liposomal formulations were comparable and lower than
      that entrapped with neutral ones. DEM was found to be more concentrated (69-95%)
      in the lipid phase of the liposome. The concentrations of DEM in the cornea,
      aqueous humor, and conjunctiva were 4.76, 2.18, and 23.32 microg/g of tissue,
      respectively. Test formulations have shown significant reductions in the IOP on
      using different treatment protocols. CONCLUSION: Preparation of liposomal
      formulations of DEM has substantially enhanced its transcorneal transport.
      Furthermore, the test formulations have shown promising and long-lasting
      intraocular pressure-lowering effect comparable with that of pilocarpine
      formulation as a control.

PMID- 17040890
TI  - The vulva is relatively insensitive to menses-induced irritation.
AB  - Skin patch testing of menses and venous blood on the vulva (labia majora) and the
      upper arm was performed to assess the potential contribution of these biological
      fluids to vulvar irritation during menstruation. After 24 and 48 hours of
      occlusive exposure, the skin of the labia majora was relatively unaffected by
      these fluids compared to the skin of the upper arm: no significant irritation was
      observed on the labia at either exposure time, but discernible irritation was
      elicited on the upper arm after 48 hours of exposure. Pre-treatment of the upper
      arm with a petrolatum-based emollient attenuated the upper arm response. Semi
      occlusive conditions also reduced the degree of upper-arm irritation elicited
      test materials and an irritant control, sodium lauryl sulfate. The relative
      insensitivity of the vulva to irritation by menses or blood was not predictable a
      priori because some irritants elicit heightened responses on the vulva relative
      to the arm (3). These results suggest that the vulva (labia majora) may be
      adapted to be less sensitive to menses-induced skin irritation than other
      anatomical sites.

PMID- 17040892
TI  - UK consultant rheumatologists' access to biological agents and views on the BSR
      Biologics Register.
AB  - OBJECTIVES: The British Society for Rheumatology Biologics Register (BSRBR) is a
      prospective cohort study to determine the efficacy and toxicity of biological
      agents in rheumatoid arthritis (RA) patients compared with RA controls. Entry of
      patients to the register is a condition of use of anti-tumour necrosis factor
      (anti-TNF) therapy in the UK, but little is known of clinicians' views of its
      usefulness. Data from the register suggest uneven provision of anti-TNF-alpha
      therapy. METHODS: A questionnaire was sent on behalf of the BSRBR to all UK
      consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy
      and their experience of working with the BSRBR. RESULTS: Response rate was 49.5%
      representing 252 consultants. Fourty-six per cent had some limitation of access
      to anti-TNF-alpha drugs, usually a financial cap (70%), even for RA patients
      meeting National Institute for Health and Clinical Excellence (NICE) criteria.
      Sixty-seven per cent could prescribe for ankylosing spondylitis (AS) or psoriatic
      arthritis (PsA) in some circumstances but only 25 and 35%, respectively, could
      prescribe according to BSR guidance. More than 50% found the workload involved in
      submitting data to the registry at least difficult, but most had favourable
      impressions of the BSRBR and thought similar registries desirable or essential
      for PsA, AS and rituximab. CONCLUSIONS: Access to anti-TNF therapy for patients
      with inflammatory arthritis is variable in the UK, even for RA where it is NICE
      approved. Access is more limited for conditions where NICE has not yet issued
      guidance. The BSRBR generates a significant workload for rheumatology staff but
      is generally well-regarded.

PMID- 17040893
TI  - Characterization of a nucleocapsid-like region and of two distinct primer
      tRNALys,2 binding sites in the endogenous retrovirus Gypsy.
AB  - Mobile LTR-retroelements comprising retroviruses and LTR-retrotransposons form a
      large part of eukaryotic genomes. Their mode of replication and abundance favour
      the notion that they are major actors in eukaryote evolution. The Gypsy
      retroelement can spread in the germ line of the fruit fly Drosophila melanogaster
      via both env-independent and env-dependent processes. Thus, Gypsy is both an
      active retrotransposon and an infectious retrovirus resembling the
      gammaretrovirus MuLV. However, unlike gammaretroviruses, the Gypsy Gag structural
      precursor is not processed into Matrix, Capsid and Nucleocapsid (NC) proteins. In
      contrast, it has features in common with Gag of the ancient yeast TY1
      retroelement. These characteristics of Gypsy make it a very interesting model to
      study replication of a retroelement at the frontier between ancient
      retrotransposons and retroviruses. We investigated Gypsy replication using an in
      vitro model system and transfection of insect cells. Results show that an
      unstructured domain of Gypsy Gag has all the properties of a retroviral NC. This
      NC-like peptide forms ribonucleoparticle-like complexes upon binding Gypsy RNA
      and directs the annealing of primer tRNA(Lys,2) to two distinct primer binding
      sites (PBS) at the genome 5' and 3' ends. Only the 5' PBS is indispensable for
      cDNA synthesis in vitro and in Drosophila cells.

PMID- 17040894
TI  - Identification of insertion hot spots for non-LTR retrotransposons: computational
      and biochemical application to Entamoeba histolytica.
AB  - The genome of the human pathogen Entamoeba histolytica contains non-long terminal
      repeat (LTR) retrotransposons, the EhLINEs and EhSINEs, which lack targeted
      insertion. We investigated the importance of local DNA structure, and sequence
      preference of the element-encoded endonuclease (EN) in selecting target sites for
      retrotransposon insertion. Pre-insertion loci were tested computationally to
      detect unique features based on DNA structure, thermodynamic considerations and
      protein interaction measures. Target sites could readily be distinguished from
      other genomic sites based on these criteria. The contribution of the EhLINE1
      encoded EN in target site selection was investigated biochemically. The sequence
      specificity of the EN was tested in vitro with a variety of mutated substrates.
      It was possible to assign a consensus sequence, 5'-GCATT-3', which was
      efficiently nicked between A-T and T-T. The upstream G residue enhanced EN
      activity, possibly serving to limit retrotransposition in the A+T-rich
      E.histolytica genome. Mutated substrates with poor EN activity showed structural
      differences compared with normal substrates. Analysis of retrotransposon
      insertion sites from a variety of organisms showed that, in general, regions of
      favorable DNA structure were recognized for retrotransposition. A combination of
      favorable DNA structure and preferred EN nicking sequence in the vicinity of this
      structure may determine the genomic hotspots for retrotransposition.

PMID- 17040895
TI  - Fluorescent T7 display phages obtained by translational frameshift.
AB  - Lytic phages form a powerful platform for the display of large cDNA libraries and
      offer the possibility to screen for interactions with almost any substrate. To
      visualize these interactions directly by fluorescence microscopy, we constructed
      fluorescent T7 phages by exploiting the flexibility of phages to incorporate
      modified versions of its capsid protein. By applying translational frameshift
      sequences, helper plasmids were constructed that expressed a fixed ratio of both
      wild-type capsid protein (gp10) and capsid protein fused to enhanced yellow
      fluorescent protein (EYFP). The frameshift sequences were inserted between the 3'
      end of the capsid gene and the sequence encoding EYFP. Fluorescent fusion
      proteins are only formed when the ribosome makes a -1 shift in reading frame
      during translation. Using standard fluorescence microscopy, we could sensitively
      monitor the enrichment of specific binders in a cDNA library displayed on
      fluorescent T7 phages. The perspectives of fluorescent display phages in the fast
      emerging field of single molecule detection and sorting technologies are
      discussed.

PMID- 17040896
TI  - ATM mediates oxidative stress-induced dephosphorylation of DNA ligase IIIalpha.
AB  - Among the three mammalian genes encoding DNA ligases, only the LIG3 gene does not
      have a homolog in lower eukaryotes. In somatic mammalian cells, the nuclear form
      of DNA ligase IIIalpha forms a stable complex with the DNA repair protein XRCC1
      that is also found only in higher eukaryotes. Recent studies have shown that
      XRCC1 participates in S phase-specific DNA repair pathways independently of DNA
      ligase IIIalpha and is constitutively phosphorylated by casein kinase II. In this
      study we demonstrate that DNA ligase IIIalpha, unlike XRCC1, is phosphorylated in
      a cell cycle-dependent manner. Specifically, DNA ligase IIIalpha is
      phosphorylated on Ser123 by the cell division cycle kinase Cdk2 beginning early
      in S phase and continuing into M phase. Interestingly, treatment of S phase cells
      with agents that cause oxygen free radicals induces the dephosphorylation of DNA
      ligase IIIalpha. This oxidative stress-induced dephosphorylation of DNA ligase
      IIIalpha is dependent upon the ATM (ataxia-telangiectasia mutated) kinase and
      appears to involve inhibition of Cdk2 and probably activation of a phosphatase.

PMID- 17040897
TI  - Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich
      elements of 3'-UTR.
AB  - Cyclooxygenase-2 (COX-2) mRNA is induced in the majority of human colorectal
      carcinomas. Transcriptional regulation plays a key role in COX-2 expression in
      human colon carcinoma cells, but post-transcriptional regulation of its mRNA is
      also critical for tumorigenesis. Expression of COX-2 mRNA is regulated by various
      cytokines, growth factors and other signals. beta-Catenin, a key transcription
      factor in the Wnt signal pathway, activates transcription of COX-2. Here we found
      that COX-2 mRNA was also substantially stabilized by activating beta-catenin in
      NIH3T3 and 293T cells. We identified the beta-catenin-responsive element in the
      proximal region of the COX-2 3'-untranslated region (3'-UTR) and showed that beta
      catenin interacted with AU-rich elements (ARE) of 3'-UTR in vitro and in vivo.
      Interestingly, beta-catenin induced the cytoplasmic localization of the RNA
      stabilizing factor, HuR, which may bind to beta-catenin in an RNA-mediated
      complex and facilitate beta-catenin-dependent stabilization of COX-2 mRNA. Taken
      together, we provided evidences for beta-catenin as an RNA-binding factor and a
      regulator of stabilization of COX-2 mRNA.

PMID- 17040898
TI  - The majority of Escherichia coli mRNAs undergo post-transcriptional modification
      in exponentially growing cells.
AB  - Polyadenylation of RNAs by poly(A) polymerase I (PAP I) in Escherichia coli plays
      a significant role in mRNA decay and general RNA quality control. However, many
      important features of this system, including the prevalence of polyadenylated
      mRNAs in the bacterium, are still poorly understood. By comparing the
      transcriptomes of wild-type and pcnB deletion strains using macroarray analysis,
      we demonstrate that >90% of E.coli open reading frames (ORFs) transcribed during
      exponential growth undergo some degree of polyadenylation by PAP I, either as
      full-length transcripts or decay intermediates. Detailed analysis of over 240
      transcripts suggests that Rho-independent transcription terminators serve as
      polyadenylation signals. Conversely, mRNAs terminated in a Rho-dependent fashion
      are probably not substrates for PAP I, but can be modified by the addition of
      long polynucleotide tails through the biosynthetic activity of polynucleotide
      phosphorylase (PNPase). Furthermore, real-time PCR analysis indicates that the
      extent of polyadenylation of individual full-length transcripts such as lpp and
      ompA varies significantly in wild-type cells. The data presented here
      demonstrates that polyadenylation in E.coli occurs much more frequently than
      previously envisioned.

PMID- 17040899
TI  - Different loop arrangements of intramolecular human telomeric (3+1) G
      quadruplexes in K+ solution.
AB  - Intramolecular G-quadruplexes formed by the human telomeric G-rich strand are
      promising anticancer targets. Here we show that four-repeat human telomeric DNA
      sequences can adopt two different intramolecular G-quadruplex folds in K+
      solution. The two structures contain the (3+1) G-tetrad core, in which three G
      tracts are oriented in one direction and the fourth in the opposite direction,
      with one double-chain-reversal and two edgewise loops, but involve different loop
      arrangements. This result indicates the robustness of the (3+1) core G-quadruplex
      topology, thereby suggesting it as an important platform for structure-based drug
      design. Our data also support the view that multiple human telomeric G-quadruplex
      conformations coexist in K+ solution. Furthermore, even small changes to flanking
      sequences can perturb the equilibrium between different coexisting G-quadruplex
      forms.

PMID- 17040900
TI  - Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of
      chondroitin sulfate required for herpes simplex virus infectivity.
AB  - We have demonstrated a defect in expression of chondroitin 4-O-sulfotransferase-1
      (C4ST-1) in murine sog9 cells, which are poorly sensitive to infection by herpes
      simplex virus type 1 (HSV-1). Sog9 cells were previously isolated as CS-deficient
      cells from gro2C cells, which were partially resistant to HSV-1 infection and
      defective in the expression of heparan sulfate (HS) because of a splice site
      mutation in the EXT1 gene encoding the HS-synthesizing enzyme. Here we detected a
      small amount of CS chains in sog9 cells with a drastic decrease in 4-O-sulfation
      compared with the parental gro2C cells. RT-PCR revealed that sog9 cells had a
      defect in the expression of C4ST-1 in addition to EXT1. Gel filtration analysis
      showed that the decrease in the amount of CS in sog9 cells was the result of a
      reduction in the length of CS chains. Transfer of C4ST-1 cDNA into sog9 cells
      (sog9-C4ST-1) restored 4-O-sulfation and amount of CS, verifying that sog9 cells
      had a specific defect in C4ST-1. Furthermore, the expression of C4ST-1 rendered
      sog9 cells significantly more susceptible to HSV-1 infection, suggesting that CS
      modified by C4ST-1 is sufficient for the binding and infectivity of HSV-1.
      Analysis of CS chains of gro2C and sog9-C4ST-1 cells revealed a considerable
      proportion of the E disaccharide unit, consistent with our recent finding that
      this unit is an essential component of the HSV receptor. These results suggest
      that C4ST-1 regulates the expression of the E disaccharide unit and the length of
      CS chains, the features that facilitate infection of cells by HSV-1.

PMID- 17040901
TI  - Hemoglobin-degrading plasmepsin II is active as a monomer.
AB  - A family of aspartic proteases called plasmepsins is important for hemoglobin
      degradation in intraerythrocytic Plasmodium parasites. Plasmepsin II (PM II) is
      the best studied member of this family. PM II and its close orthologs and
      paralogs form homodimers with extensive interfaces in all known crystal
      structures. This raised the question whether the homodimer is the functional
      subunit of plasmepsins in solution. We have used gel filtration chromatography,
      site-directed mutagenesis, and analytical ultracentrifugation to study the
      oligomeric status of PM II in solution. Our results reveal that PM II exists
      mainly as a monomer in solution and that the monomer is fully functional for
      catalysis. A hydrophobic loop at the PM II monomer surface, which would be buried
      in a PM II dimer, is shown to be essential for the hemoglobin degradation
      capability of PM II.

PMID- 17040902
TI  - Induction of the heat shock pathway during hypoxia requires regulation of heat
      shock factor by hypoxia-inducible factor-1.
AB  - Activation of heat shock proteins (Hsps) is critical to adaptation to low oxygen
      levels (hypoxia) and for enduring the oxidative stress of reoxygenation. Hsps are
      known to be regulated by heat shock factor (Hsf), but our results demonstrate an
      unexpected regulatory link between the oxygen-sensing and heat shock pathways.
      Hsf transcription is up-regulated during hypoxia due to direct binding by hypoxia
      inducible factor-1 (HIF-1) to HIF-1 response elements in an Hsf intron. This
      increase in Hsf transcripts is necessary for full Hsp induction during hypoxia
      and reoxygenation. The HIF-1-dependent increase in Hsps has a functional impact,
      as reduced production of Hsps decreases viability of adult flies exposed to
      hypoxia and reoxygenation. Thus, HIF-1 control of Hsf transcriptional levels is a
      regulatory mechanism for sensitizing heat shock pathway activity in order to
      maximize production of protective Hsps. This cross-regulation represents a
      mechanism by which the low oxygen response pathway has assimilated complex new
      functions by regulating the key transcriptional activator of the heat shock
      pathway.

PMID- 17040903
TI  - Trypanosoma seryl-tRNA synthetase is a metazoan-like enzyme with high affinity
      for tRNASec.
AB  - Trypanosomatids are important human pathogens that form a basal branch of
      eukaryotes. Their evolutionary history is still unclear as are many aspects of
      their molecular biology. Here we characterize essential components required for
      the incorporation of serine and selenocysteine into the proteome of Trypanosoma.
      First, the biological function of a putative Trypanosoma seryl-tRNA synthetase
      was characterized in vivo. Secondly, the molecular recognition by Trypanosoma
      seryl-tRNA synthetase of its cognate tRNAs was dissected in vitro. The cellular
      distribution of tRNA(Sec) was studied, and the catalytic constants of its
      aminoacylation were determined. These were found to be markedly different from
      those reported in other organisms, indicating that this reaction is particularly
      efficient in trypanosomatids. Our functional data were analyzed in the context of
      a new phylogenetic analysis of eukaryotic seryl-tRNA synthetases that includes
      Trypanosoma and Leishmania sequences. Our results show that trypanosomatid seryl
      tRNA synthetases are functionally and evolutionarily more closely related to
      their metazoan homologous enzymes than to other eukaryotic enzymes. This
      conclusion is supported by sequence synapomorphies that clearly connect metazoan
      and trypanosomatid seryl-tRNA synthetases.

PMID- 17040904
TI  - Molecular mechanisms of import of peroxisome-targeting signal type 2 (PTS2)
      proteins by PTS2 receptor Pex7p and PTS1 receptor Pex5pL.
AB  - In the present study, we investigated molecular mechanisms underlying the import
      of peroxisome-targeting signal type 2 (PTS2) proteins into peroxisomes. Purified
      Chinese hamster Pex7p that had been expressed in an Sf9/baculovirus system was
      biologically active in several assays such as those for PTS2 binding and
      assessing the restoration of the impaired PTS2 protein import in Chinese hamster
      ovary (CHO) pex7 mutant ZPG207. Pex7p was eluted as a monomer in gel filtration
      chromatography. Moreover, the mutation of the highly conserved cysteine residue
      suggested to be involved in the dimer formation did not affect the complementing
      activity in ZPG207 cells. Together, Pex7p more likely functions as a monomer.
      Together with PTS1 protein, the Pex7p-PTS2 protein complex was bound to Pex5pL,
      the longer form of Pex5p, which was prerequisite for the translocation of Pex7p
      PTS2 protein complexes. Pex5pL-(Pex7p-PTS2 protein) complexes were detectable in
      wild-type CHO-K1 cells and were apparently more stable in pex14 CHO cells
      deficient in the entry site of the matrix proteins, whereas only the Pex7p-PTS2
      protein complex was discernible in a Pex5pL-defective pex5 CHO mutant. Pex7p-PTS2
      proteins bound to Pex14p via Pex5pL. In contrast, PTS2 protein-bound Pex7p as
      well as Pex7p directly and equally interacted with Pex13p, implying that the PTS2
      cargo may be released at Pex13p. Furthermore, we detected the Pex13p complexes
      likewise formed with Pex5pL-bound Pex7p-PTS2 proteins. Thus, the Pex7p-mediated
      PTS2 protein import shares most of the steps with the Pex5p-dependent PTS1 import
      machinery but is likely distinct at the cargo-releasing stage.

PMID- 17040905
TI  - The functional effects of physical interactions among Toll-like receptors 7, 8,
      and 9.
AB  - Toll-like receptors (TLRs) TLR1, TLR2, TLR4, and TLR6 are evolutionarily
      conserved, highly homologous, and localized to plasma membranes of host cells and
      recognize pathogen-associated molecular patterns (PAMPs) derived from bacterial
      membranes. These receptors cooperate in a pairwise combination to elicit or
      inhibit the inflammatory signals in response to certain PAMPs. The other TLRs
      that are evolutionarily closely related and highly homologous are TLR7, TLR8, and
      TLR9. They are all confined to the membranes of endosomes and recognize similar
      molecular structures, the oligonucleotide-based PAMPs. However, the cooperative
      interactions among these receptors that may modulate the inflammatory signaling
      in response to their cognate agonists are not reported. We report here for the
      first time the functional effects of one TLR on the other among TLR7, TLR8, and
      TLR9. The results indicate that TLR8 inhibits TLR7 and TLR9, and TLR9 inhibits
      TLR7 but not vice versa in HEK293 cells transfected with TLRs in a pairwise
      combination. This is concluded by selectively activating one TLR over the other
      by using small molecule TLR agonists. We also show that these inhibitory
      interactions are the result of direct or indirect physical interactions between
      the TLRs. The murine TLR8 that does not respond to any known human TLR8 agonists
      also inhibits both murine and human TLR7. The implications of the inhibitory
      interactions among these TLRs in host-pathogen recognition and subsequent
      inflammatory responses are not obvious. However, given the complexity in
      expression pattern in a particular cell type and the variation in distribution
      and response to different pathogens and stress signals in different cell types,
      the inhibitory physical interactions among these TLRs may play a role in
      balancing the inflammatory outcome from a given cell type to a specific
      challenge.

PMID- 17040906
TI  - Mitochondrial production of reactive oxygen species mediate dicumarol-induced
      cytotoxicity in cancer cells.
AB  - Dicumarol is a naturally occurring anticoagulant derived from coumarin that
      induces cytotoxicity and oxidative stress in human pancreatic cancer cells
      (Cullen, J. J., Hinkhouse, M. M., Grady, M., Gaut, A. W., Liu, J., Zhang, Y.,
      Weydert, C. J. D., Domann, F. E., and Oberley, L. W. (2003) Cancer Res. 63, 5513
      5520). Although dicumarol has been used as an inhibitor of the two-electron
      reductase NAD(P)H:quinone oxidoreductase (NQO1), dicumarol is also thought to
      affect quinone-mediated electron transfer reactions in the mitochondria, leading
      to the production of superoxide (O2*-) and hydrogen peroxide (H(2)O(2)). We
      hypothesized that mitochondrial production of reactive oxygen species mediates
      the increased susceptibility of pancreatic cancer cells to dicumarol-induced
      metabolic oxidative stress. Dicumarol decreased clonogenic survival equally in
      both MDA-MB-468 NQO1(-) and MDA-MB-468 NQO1+ breast cancer cells. Dicumarol
      decreased clonogenic survival in the transformed fibroblast cell line IMRSV-90
      compared with the IMR-90 cell line. Dicumarol, with the addition of mitochondrial
      electron transport chain blockers, decreased clonogenic cell survival in human
      pancreatic cancer cells and increased superoxide levels. Dicumarol with the
      mitochondrial electron transport chain blocker antimycin A decreased clonogenic
      survival and increased superoxide levels in cells with functional mitochondria
      but had little effect on cancer cells without functional mitochondria.
      Overexpression of manganese superoxide dismutase and mitochondrial-targeted
      catalase with adenoviral vectors reversed the dicumarol-induced cytotoxicity and
      reversed fluorescence of the oxidation-sensitive probe. We conclude mitochondrial
      production of reactive oxygen species mediates the increased susceptibility of
      cancer cells to dicumarol-induced cytotoxicity.

PMID- 17040907
TI  - Antiangiogenic antithrombin blocks the heparan sulfate-dependent binding of
      proangiogenic growth factors to their endothelial cell receptors: evidence for
      differential binding of antiangiogenic and anticoagulant forms of antithrombin to
      proangiogenic heparan sulfate domains.
AB  - The anticoagulant serpin antithrombin acquires a potent antiangiogenic activity
      upon undergoing conformational alterations to cleaved or latent forms. Here we
      show that antithrombin antiangiogenic activity is mediated at least in part
      through the ability of the conformationally altered serpin to block the
      proangiogenic growth factors fibroblast growth factor (FGF)-2 and vascular
      endothelial growth factor (VEGF) from forming signaling competent ternary
      complexes with their protein receptors and heparan sulfate co-receptors on
      endothelial cells. Cleaved and latent but not native forms of antithrombin
      blocked the formation of FGF-2-FGF receptor-1 ectodomain-heparin ternary
      complexes, and the dimerization of these complexes in solution and similarly
      inhibited the formation of FGF-2-heparin binary complexes and their dimerization.
      Only antiangiogenic forms of antithrombin likewise inhibited (125)I-FGF-2 binding
      to its low affinity heparan sulfate co-receptor and blocked FGF receptor-1
      autophosphorylation and p42/44 MAP kinase phosphorylation in cultured human
      umbilical vein endothelial cells (HUVECs). Moreover, treatment of HUVECs with
      heparinase III to specifically eliminate the FGF-2 heparan sulfate co-receptor
      suppressed the ability of antiangiogenic antithrombin to inhibit growth factor
      stimulated proliferation. Antiangiogenic antithrombin inhibited full-length
      VEGF(165) stimulation of HUVEC proliferation but did not affect the stimulation
      of cells by the heparin-binding domain-deleted VEGF(121). Taken together, these
      results demonstrate that antiangiogenic forms of antithrombin block the
      proangiogenic effects of FGF-2 and VEGF on endothelial cells by competing with
      the growth factors for binding the heparan sulfate co-receptor, which mediates
      growth factor-receptor interactions. Moreover, the inability of native
      antithrombin to bind this co-receptor implies that native and conformationally
      altered forms of antithrombin differentially bind proangiogenic heparan sulfate
      domains.

PMID- 17040908
TI  - The cysteine-rich domain of snake venom metalloproteinases is a ligand for von
      Willebrand factor A domains: role in substrate targeting.
AB  - Snake venom metalloproteinases (SVMPs) are members of the Reprolysin family of
      metalloproteinases to which the ADAM (a disintegrin and metalloproteinase)
      proteins also belong. The disintegrin-like/cysteine-rich domains of the ADAMs
      have been implicated in their function. In the case of the SVMPs, we hypothesized
      that these domains could function to target the metalloproteinases to key
      extracellular matrix proteins or cell surface proteins. Initially we detected
      interaction of collagen XIV, a fibril-associated collagen with interrupted triple
      helices containing von Willebrand factor A (VWA) domains, with the PIII SVMP
      catrocollastatin. Next we investigated whether other VWA domain-containing matrix
      proteins could support the binding of PIII SVMPs. Using surface plasmon
      resonance, the PIII SVMP jararhagin and a recombinant cysteine-rich domain from a
      PIII SVMP were demonstrated to bind to collagen XIV, collagen XII, and matrilins
      1, 3, and 4. Jararhagin was shown to cleave these proteins predominantly at sites
      localized at or near the VWA domains suggesting that it is the VWA domains to
      which the PIII SVMPs are binding via their cysteine-rich domain. In light of the
      fact that these extracellular matrix proteins function to stabilize matrix,
      targeting the SVMPs to these proteins followed by their specific cleavage could
      promote the destabilization of extracellular matrix and cell-matrix interactions
      and in the case of capillaries could contribute to their disruption and
      hemorrhage. Although there is only limited structural homology shared by the
      cysteine-rich domains of the PIII SVMPs and the ADAMs our results suggest an
      analogous function for the cysteine-rich domains in certain members of the
      expanded ADAM family of proteins to target them to VWA domain-containing
      proteins.

PMID- 17040909
TI  - TorT, a member of a new periplasmic binding protein family, triggers induction of
      the Tor respiratory system upon trimethylamine N-oxide electron-acceptor binding
      in Escherichia coli.
AB  - In anaerobiosis, Escherichia coli can use trimethylamine N-oxide (TMAO) as a
      terminal electron acceptor. Reduction of TMAO in trimethylamine (TMA) is mainly
      performed by the respiratory TMAO reductase. This system is encoded by the torCAD
      operon, which is induced in the presence of TMAO. This regulation involves a two
      component system comprising TorS, an unorthodox histidine kinase, and TorR, a
      response regulator. A third protein, TorT, sharing homologies with periplasmic
      binding proteins, plays a key role in this regulation because disruption of the
      torT gene abolishes tor expression. In this study we showed that TMAO protects
      TorT against degradation by the GluC endoproteinase and modifies its temperature
      induced CD spectrum. We also isolated a TorT negative mutant that is no longer
      protected by TMAO from degradation by GluC. Isothermal titration calorimetry
      confirmed that TorT binds TMAO with a binding constant of 150 mum. Therefore, we
      conclude that TorT binds TMAO and that this binding promotes a conformational
      change of TorT. We also showed that TorT interacts with the periplasmic domain of
      TorS in both the presence and absence of TMAO but the TorT-TMAO complex induces a
      higher GluC protection of TorS than TorT alone. These results support the idea
      that TMAO binding to TorT induces a cascade of conformational changes from TorT
      to TorS, leading to TorS activation. We identified several homologues of the TorT
      protein that define a new family of periplasmic binding proteins. We thus propose
      that the members of this family bind TMAO or related compounds and that they are
      involved in signal transduction or even substrate transport.

PMID- 17040910
TI  - Investigation of the dimer interface and substrate specificity of prolyl
      dipeptidase DPP8.
AB  - DPP8 belongs to the family of prolyl dipeptidases, which are capable of cleaving
      the peptide bond after a penultimate proline residue. Unlike DPP-IV, a drug
      target for type II diabetes, no information is available on the crystal structure
      of DPP8, the regulation of its enzymatic activity, or its substrate specificity.
      In this study, using analytical ultracentrifugation and native gel
      electrophoresis, we show that the DPP8 protein is predominantly dimeric when
      purified or in the cell extracts. Four conserved residues in the C-terminal loop
      of DPP8 (Phe(822), Val(833), Tyr(844), and His(859)), corresponding to those
      located at the dimer interface of DPP-IV, were individually mutated to Ala.
      Surprisingly, unlike DPP-IV, these single-site mutations abolished the enzymatic
      activity of DPP8 without disrupting its quaternary structure, indicating that
      dimerization itself is not sufficient for the optimal enzymatic activity of DPP8.
      Moreover, these mutations not only decreased k(cat), as did the corresponding DPP
      IV mutations, but also dramatically increased K(m). We further show that the K(m)
      effect is independent of the substrate assayed. Finally, we identified the
      distinctive and strict substrate selectivity of DPP8 for hydrophobic or basic
      residues at the P2 site, which is in sharp contrast to the much less
      discriminative substrate specificity of DPP-IV. Our study has identified the
      residues absolutely required for the optimal activity of DPP8 and its unique
      substrate specificity. This study extends the functional importance of the C
      terminal loop to the whole family of prolyl dipeptidases.

PMID- 17040911
TI  - Protease domain glycans affect oligomerization, disulfide bond formation, and
      stability of the meprin A metalloprotease homo-oligomer.
AB  - The meprin A homo-oligomer is a highly glycosylated, secreted zinc
      metalloprotease of the astacin family and metzincin superfamily. This isoform of
      meprin is composed of disulfide-bonded dimers of alpha subunits that further
      associate to form large, secreted megadalton complexes of 10 or more subunits.
      The aim of this study was to determine the sites of glycan attachment and to
      assess their ability to affect the formation and stability of the homo-oligomer.
      Nine of the ten potential N-linked glycosylation sites (Asn-41, Asn-152, Asn-234,
      Asn-270, Asn-330, Asn-426, Asn-452, Asn-546, and Asn-553) were found to be
      glycosylated in recombinant mouse meprin A using chemical and enzymatic
      deglycosylation methods and electrospray ionization mass spectrometry. Chemical
      cross-linking demonstrated that carbohydrates are at or near the noncovalent
      subunit interface. The removal of two glycans in the protease domain at Asn-234
      and Asn-270, as well as one in the tumor necrosis factor receptor-associated
      factor domain at Asn-452, by a deglycosidase under nondenaturing conditions
      decreased the chemical and thermal stability of the homo-oligomer without
      affecting quaternary structure. Site-directed mutagenesis demonstrated that no
      single glycan was essential for oligomer formation; however, the combined absence
      of the glycans at Asn-152 and Asn-270 in the protease domain hindered
      intersubunit disulfide bond formation, prevented noncovalent associations, and
      abolished enzymatic activity. These studies provide insights into the role of
      glycans in the biosynthesis, activity, and stability of this extracellular
      protease.

PMID- 17040912
TI  - A new class of signal transducer in His-Asp phosphorelay systems.
AB  - Nitrate transport activity of the LtnT permease of the cyanobacterium
      Synechococcus elongatus is activated when LtnA, a response regulator without an
      effector domain, is phosphorylated by LtnB, a hybrid histidine kinase. We
      identified a protein (LtnC) that is required for activation of LtnT. LtnC
      consists of an N-terminal histidine-containing phosphoacceptor (HisKA) domain, a
      receiver domain, and a unique C-terminal domain found in some cyanobacterial
      proteins. Because LtnC lacks an ATP-binding kinase domain of a histidine kinase,
      it is incapable of autophosphorylation, but LtnC is phosphorylated by LtnA. The
      histidine residue in the HisKA domain but not the aspartate residue in the
      receiver domain is essential for phosphorylation of LtnC and activation of LtnT.
      LtnC phosphorylation leads to oligomerization of the protein. Fusion of the C
      terminal domain of LtnC to glutathione S-transferase, which forms oligomers, also
      activates LtnT, suggesting that oligomerization of the LtnC C-terminal domain
      causes LtnT activation. These results indicate that the C-terminal domain of LtnC
      acts as an effector domain that directs the output of the signal from the
      phosphorelay system. The two-step (His-Asp-His) phosphorelay system, composed of
      the LtnB, LtnA, and LtnC proteins, is distinct from the known phosphorelay
      systems, namely, the typical two-component system (His-Asp) and the multistep
      phosphorelay system (His-Asp-His-Asp), because the HisKA domain of LtnC is the
      terminal phosphoacceptor that determines the signal output. LtnC is a new class
      of signal transducer in His-Asp phosphorelay systems that contains a HisKA domain
      and an effector domain.

PMID- 17040913
TI  - An unusual twin-his arrangement in the pore of ammonia channels is essential for
      substrate conductance.
AB  - Amt proteins constitute a class of ubiquitous integral membrane proteins that
      mediate movement of ammonium across cell membranes. They are homotrimers, in
      which each subunit contains a narrow pore through which substrate transport
      occurs. Two conserved histidine residues in the pore have been proposed to be
      necessary for ammonia conductance. By analyzing 14 engineered polar and non-polar
      variants of these histidines, in Escherichia coli AmtB, we show that both
      histidines are absolutely required for optimum substrate conductance. Crystal
      structures of variants confirm that substitution of the histidine residues does
      not affect AmtB structure. In a subgroup of Amt proteins, found only in fungi,
      one of the histidines is replaced by glutamate. The equivalent substitution in E.
      coli AmtB is partially active, and the structure of this variant suggests that
      the glutamate side chain can make similar interactions to those made by
      histidine.

PMID- 17040914
TI  - Molecular determinants for G protein betagamma modulation of ionotropic glycine
      receptors.
AB  - The ligand-gated ion channel superfamily plays a critical role in neuronal
      excitability. The functions of glycine receptor (GlyR) and nicotinic
      acetylcholine receptor are modulated by G protein betagamma subunits. The
      molecular determinants for this functional modulation, however, are still
      unknown. Studying mutant receptors, we identified two basic amino acid motifs
      within the large intracellular loop of the GlyR alpha(1) subunit that are
      critical for binding and functional modulation by Gbetagamma. Mutations within
      these sequences demonstrated that all of the residues detected are important for
      Gbetagamma modulation, although both motifs are necessary for full binding.
      Molecular modeling predicts that these sites are alpha-helixes near transmembrane
      domains 3 and 4, near to the lipid bilayer and highly electropositive. Our
      results demonstrate for the first time the sites for G protein betagamma subunit
      modulation on GlyRs and provide a new framework regarding the ligand-gated ion
      channel superfamily regulation by intracellular signaling.

PMID- 17040915
TI  - The DNA binding preference of RAD52 and RAD59 proteins: implications for RAD52
      and RAD59 protein function in homologous recombination.
AB  - We examined the double-stranded DNA (dsDNA) binding preference of the
      Saccharomyces cerevisiae Rad52 protein and its homologue, the Rad59 protein. In
      nuclease protection assays both proteins protected an internal sequence and the
      dsDNA ends equally well. Similarly, using electrophoretic mobility shift assays,
      we found the affinity of both Rad52 and Rad59 proteins for DNA ends to be
      comparable with their affinity for internal sequences. The protein-DNA complexes
      were also directly visualized using atomic force microscopy. Both proteins formed
      discrete complexes, which were primarily found (90-94%) at internal dsDNA sites.
      We also measured the DNA end binding behavior of human Rad52 protein and found a
      slight preference for dsDNA ends. Thus, these proteins have no strong preference
      for dsDNA ends over internal sites, which is inconsistent with their function at
      a step of dsDNA break repair that precedes DNA processing. Therefore, we conclude
      that S. cerevisiae Rad52 and Rad59 proteins and their eukaryotic counterparts
      function by binding to single-stranded DNA formed as intermediates of
      recombination rather than by binding to the unprocessed DNA double-strand break.

PMID- 17040916
TI  - Mammalian transcription in support of hybrid mRNA and protein synthesis in testis
      and lung.
AB  - Post-transcriptional mechanisms including differential splicing expand the
      protein repertoire beyond that provided by the one gene-one protein model. Trans
      splicing has been observed in mammalian systems but is low level (sometimes
      referred to as noise), and a contribution to hybrid protein expression is
      unclear. In the study of rat sperm tail proteins a cDNA, called 1038, was
      isolated representing a hybrid mRNA derived in part from the ornithine
      decarboxylase antizyme 3 (Oaz3) gene located on rat chromosome 2 fused to
      sequences encoded by a novel gene on chromosome 4. Cytoplasmic Oaz3 mRNA is
      completely testis specific. However, in several tissues Oaz3 is transcribed and
      contributes to hybrid 1038 mRNA synthesis, without concurrent Oaz3 mRNA
      synthesis. 1038 mRNA directs synthesis of a hybrid 14-kDa protein, part
      chromosome 2- and part chromosome 4-derived as shown in vitro and in transfected
      cells. Antisera that recognize a chromosome 4-encoded C-terminal peptide confirm
      the hybrid character of endogenous 14-kDa protein and its presence in sperm tail
      structures and 1038-positive tissue. Our data suggest that the testis-specific
      OAZ3 gene may be an example of a mammalian gene that in several tissues is
      transcribed to contribute to a hybrid mRNA and protein. This finding expands the
      repertoire of known mechanisms available to cells to generate proteome diversity.

PMID- 17040917
TI  - Molecular adaptation and allostery in plant pantothenate synthetases.
AB  - Pantothenate synthetase catalyzes the ATP-dependent condensation of pantoate and
      beta-alanine to yield pantothenate, the essential precursor to coenzyme A.
      Bacterial and plant pantothenate synthetases are dimeric enzymes that share
      significant sequence identity. Here we show that the two-step reaction mechanism
      of pantothenate synthetase is conserved between the enzymes from Arabidopsis
      thaliana and Escherichia coli. Strikingly, though, the Arabidopsis enzyme
      exhibits large allosteric effects, whereas the Escherichia coli enzyme displays
      essentially non-allosteric behavior. Our data suggest that specific subunit
      contacts were selected and maintained in the plant lineage of the pantothenate
      synthetase protein family and that the resulting allosteric interactions are
      balanced for efficient catalysis at low pantoate levels. This is supported by
      mutations in the putative subunit interface of Arabidopsis pantothenate
      synthetase, which strongly attenuated or otherwise modified its allosteric
      properties but did not affect the dimeric state of the enzyme. At the molecular
      level, plant pantothenate synthetases exemplify functional adaptation through
      allostery and without alterations to the active site architecture. We propose
      that the allosteric behavior confers a selective advantage in the context of the
      subcellular compartmentation of pantothenate biosynthesis in plants.

PMID- 17040918
TI  - The Arabidopsis protein kinase PTI1-2 is activated by convergent phosphatidic
      acid and oxidative stress signaling pathways downstream of PDK1 and OXI1.
AB  - Arabidopsis PDK1 activity is regulated by binding to the lipid phosphatidic acid
      (PA) resulting in activation of the oxidative stress-response protein kinase
      OXI1/AGC2-1. Thus there is an inferred link between lipid signaling and oxidative
      stress signaling modules. Among a panel of hormones and stresses tested, we found
      that, in addition to PA, the fungal elicitor xylanase activated PDK1, suggesting
      that PDK1 has a role in plant pathogen defense mechanisms. The downstream OXI1
      was activated by additional stress factors, including PA, H(2)O(2), and partially
      by xylanase. We have isolated an interacting partner of OXI1, a Ser/Thr kinase
      (PTI1-2), which is downstream of OXI1. Its sequence closely resembles the tomato
      Pti kinase, which has been implicated in the hypersensitive response, a localized
      programmed cell death that occurs at the site of pathogen infection. PTI1-2 is
      activated by the same stresses/elicitors as OXI1 and additionally flagellin. We
      have used RNA interference to knock out the expression of PDK1 and OXI1 and to
      study the effects on PTI1-2 activity. We show that specific lipid signaling
      pathways converge on PTI1-2 via the PDK1-OXI1 axis, whereas H(2)O(2) and
      flagellin signals to OXI1-PTI1-2 via a PDK1-independent pathway. PTI1-2
      represents a new downstream component that integrates diverse lipid and reactive
      oxygen stress signals and functions closely with OXI1.

PMID- 17040919
TI  - Hydrophobic interface between two regulators of K+ conductance domains critical
      for calcium-dependent activation of large conductance Ca2+-activated K+ channels.
AB  - It has been suggested that the large conductance Ca(2)+-activated K(+) channel
      contains one or more domains known as regulators of K(+) conductance (RCK) in its
      cytosolic C terminus. Here, we show that the second RCK domain (RCK2) is
      functionally important and that it forms a heterodimer with RCK1 via a
      hydrophobic interface. Mutant channels lacking RCK2 are nonfunctional despite
      their tetramerization and surface expression. The hydrophobic residues that are
      expected to form an interface between RCK1 and RCK2, based on the crystal
      structure of the bacterial MthK channel, are well conserved, and the interactions
      of these residues were confirmed by mutant cycle analysis. The hydrophobic
      interaction appears to be critical for the Ca(2+)-dependent gating of the large
      conductance Ca(2+)-activated K(+) channel.

PMID- 17040920
TI  - Inherent limitations in protein-protein docking procedures.
AB  - MOTIVATION: The limited success rate of protein-protein docking procedures is
      generally attributed to structure differences between the bound and unbound
      states of the molecules. Herein we analyze a large dataset of protein-protein
      docking results and identify additional parameters that affect the performance of
      docking procedures. RESULTS: We find that the distinction between nearly correct
      models (NCMs) and decoys depends on the size of the interface to be predicted
      thus setting a limit to the prediction ability of docking procedures,
      particularly those in which the geometric complementarity descriptor is dominant.
      The geometric complementarity score in grid-based docking carries a large
      statistical error which further reduces the distinction between NCMs and decoys.
      We propose a method for correcting the statistical error and show that the
      distinction is improved when the docking models are ranked by statistically
      equivalent scores. AVAILABILITY: MolFit can be downloaded from our website
      http://www.weizmann.ac.il/Chemical_Research_Support/molfit. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17040921
TI  - Striosomes and mood dysfunction in Huntington's disease.
AB  - Variable phenotype is common in neurological disorders with single-gene
      inheritance patterns. In Huntington's disease, mood and cognitive symptoms are
      variably co-expressed with motor symptoms. There is also variable degeneration of
      neurons in the two major neurochemical compartments of the striatum, the
      striosomes and the extrastriosomal matrix. To determine whether the phenotypic
      variability in Huntington's disease is related to this compartmental
      organization, we carried out a double-blind study in which we used GABA(A)
      receptor immunohistochemistry to analyse the status of striosomes and matrix in
      the brains of 35 Huntington's disease cases and 13 control cases, and collected
      detailed data on the clinical symptomatology expressed by the patients from
      family members and records. We report here a significant association between
      pronounced mood dysfunction in Huntington's disease patients and differential
      loss of the GABA(A) receptor marker in striosomes of the striatum. This
      association held for both clinical onset and end-stage assessments of symptoms.
      The cases with accentuated striosome abnormality further exhibited later onset
      age, lower disease grade and lower CAG repeat length in the HD gene. We found no
      independent association, however, between CAG repeat length or age of onset and
      mood dysfunction. We suggest that variation in clinical symptomatology in
      Huntington's disease is associated with variation in the relative abnormality of
      GABA(A) receptor expression in the striosome and matrix compartments of the
      striatum, and that striosome-related circuits may modulate mood functioning.

PMID- 17040922
TI  - Bactericidal agents in the treatment of MRSA infections--the potential role of
      daptomycin.
AB  - Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains
      have emerged as serious pathogens. These strains are often multiresistant to
      several antibiotic classes and are a major cause of serious hospital- and now
      community-acquired infections and associated morbidity and mortality. As a result
      of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are
      widely used as first-line therapy for serious MRSA infections. However, the
      emergence of glycopeptide tolerance and resistance has complicated treatment and
      there remains a clinical need for new antibiotics with suitable pharmacokinetic
      properties with activity against MRSA and other gram-positive pathogens.
      Infections caused by MRSA and other bacteria usually respond as well to
      bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence
      that rapid bacterial killing has potential clinical advantages over
      bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic
      lipopeptides, shows rapid bactericidal activity against S. aureus, including
      strains tolerant or resistant to other agents. This review outlines the methods
      by which bactericidal and bacteriostatic properties are defined and tested,
      discusses the potential importance of bactericidal therapy in MRSA and other
      infections and examines the potential role of daptomycin in treatment.

PMID- 17040923
TI  - Analysis of the mechanisms of fluoroquinolone resistance in urinary tract
      pathogens.
AB  - OBJECTIVES: To characterize the mechanisms of fluoroquinolone resistance in
      urinary tract pathogens exhibiting a multiple antibiotic resistance phenotype as
      well as a high-level resistance to fluoroquinolones. METHODS: Nineteen
      Escherichia coli urinary tract infection pathogens exhibiting high-level
      resistance to fluoroquinolones were characterized in this study. Alterations in
      outer membrane proteins (OMPs) and lipopolysaccharide (LPS) were analysed by
      PAGE. Changes to the quinolone resistance-determining regions (QRDRs) of GyrA and
      ParC were determined by PCR and DNA sequencing. The presence of the qnrA gene was
      determined by PCR amplification. Ciprofloxacin uptake was determined
      spectrophotometrically using the quinolone accumulation assay. RESULTS: OMP
      analysis showed decreased expression, the absence of certain proteins or the
      presence of proteins with altered molecular weights when compared with wild-type
      strains. Most isolates possessed a smooth LPS phenotype. Isolates had double
      mutations in GyrA codons 83 and 87, in addition to a ParC alteration at Ser
      80/Glu-84. Isolates accumulated varying levels of ciprofloxacin, and upon the
      addition of carbonyl cyanide m-chlorophenylhydrazone, increased accumulation was
      observed in all instances. E. coli isolates with a rough LPS phenotype appeared
      to accumulate higher levels of ciprofloxacin compared with those with a smooth
      LPS phenotype expressing OmpF normally, or even those not possessing OmpF. All E.
      coli isolates tested demonstrated active efflux of ciprofloxacin. Plasmid
      mediated quinolone resistance (presence of the qnrA gene) was observed in 36.8%
      of isolates. CONCLUSIONS: A combination of target gene alterations, altered OM
      permeability, presence of the qnrA gene and active efflux appear to act together
      to produce a high-level, multiresistance phenotype.

PMID- 17040924
TI  - Prevention of HIV and sexually transmitted diseases in high risk social networks
      of young Roma (Gypsy) men in Bulgaria: randomised controlled trial.
AB  - OBJECTIVE: To determine the effects of a behavioural intervention for prevention
      of HIV and sexually transmitted diseases that identified, trained, and engaged
      leaders of Roma (Gypsy) men's social networks to counsel their own network
      members. DESIGN: A two arm randomised controlled trial. SETTING: A disadvantaged,
      impoverished Roma settlement in Bulgaria. PARTICIPANTS: 286 Roma men from 52
      social networks recruited in the community. INTERVENTION: At baseline all
      participants were assessed for HIV risk behaviour, tested and treated for
      sexually transmitted diseases, counselled in risk reduction, and randomised to
      intervention or control groups. Network leaders learnt how to counsel their
      social network members on risk prevention. Networks were followed up three and 12
      months after the intervention to determine evidence of risk reduction. MAIN
      OUTCOME MEASURE: Occurrence of unprotected intercourse during the three months
      before each assessment. RESULTS: Reported prevalence of unprotected intercourse
      in the intervention group fell more than in control group (from 81% and 80%,
      respectively, at baseline to 65% and 75% at three months and 71% and 86% at 12
      months). Changes were more pronounced among men with casual partners. Effects
      remained strong at long term follow-up, consistent with changes in risk reduction
      norms in the social network. Other measures of risk reduction corroborated the
      intervention's effects. CONCLUSIONS: Endorsement and advice on HIV prevention
      from the leader of a social network produces well maintained change in the
      reported sexual practices in members of that network. This model has particular
      relevance for health interventions in populations such as Roma who may be
      distrustful of outsiders. TRIAL REGISTRATION: Clinical Trials NCT00310973.

PMID- 17040925
TI  - Effect of baseline serum albumin concentration on outcome of resuscitation with
      albumin or saline in patients in intensive care units: analysis of data from the
      saline versus albumin fluid evaluation (SAFE) study.
AB  - OBJECTIVE: To determine whether outcomes of resuscitation with albumin or saline
      in the intensive care unit depend on patients' baseline serum albumin
      concentration. DESIGN: Analysis of data from a double blind, randomised
      controlled trial. SETTING: Intensive care units of 16 hospitals in Australia and
      New Zealand. PARTICIPANTS: 6045 participants in the saline versus albumin fluid
      evaluation (SAFE) study. INTERVENTIONS: Fluid resuscitation with 4% albumin or
      saline in patients with a baseline serum albumin concentration of 25 g/l or less
      or more than 25 g/l. MAIN OUTCOME MEASURES: Primary outcome was all cause
      mortality at 28 days. Secondary outcomes were length of stay in the intensive
      care unit, length of stay in hospital, duration of renal replacement therapy, and
      duration of mechanical ventilation. MAIN RESULTS: The odds ratios for death for
      albumin compared with saline for patients with a baseline serum albumin
      concentration of 25 g/l or less and more than 25 g/l were 0.87 and 1.09,
      respectively (ratio of odds ratios 0.80, 95% confidence interval 0.63 to 1.02);
      P=0.08 for heterogeneity. No significant interaction was found between baseline
      serum albumin concentration as a continuous variable and the effect of albumin
      and saline on mortality. No consistent interaction was found between baseline
      serum albumin concentration and treatment effects on length of stay in the
      intensive care unit, length of hospital stay, duration of renal replacement
      therapy, or duration of mechanical ventilation. CONCLUSION: The outcomes of
      resuscitation with albumin and saline are similar irrespective of patients'
      baseline serum albumin concentration. TRIAL REGISTRATION: ISRCTN76588266.

PMID- 17040926
TI  - Self management of arthritis in primary care: randomised controlled trial.
AB  - OBJECTIVE: To evaluate clinical effectiveness of a self management programme for
      arthritis in patients in primary care with osteoarthritis. DESIGN: Randomised
      controlled trial. SETTING: 74 general practices in the United Kingdom.
      PARTICIPANTS: 812 patients aged 50 and over with osteoarthritis of hips or knees
      (or both) and pain or disability (or both). INTERVENTION: Participants were
      randomised to six sessions of self management of arthritis and an education
      booklet (intervention group) or the education booklet alone (control group). MAIN
      OUTCOME MEASURES: Primary outcome was quality of life, as assessed by the short
      form health survey (SF-36). Several other physical and psychosocial secondary
      outcomes were assessed. Data were collected at baseline, four months, and 12
      months. RESULTS: Response rates were 80% and 76% at four and 12 months. The two
      groups showed significant differences at 12 months on the anxiety subscore of the
      hospital anxiety and depression scale (mean difference -0.62, 95% confidence
      interval -1.08 to -0.16), arthritis self efficacy scale for pain (0.98, 0.07 to
      1.89), and self efficacy for other aspects of management (1.58, 0.25 to 2.90).
      Results were similar for intention to treat and per protocol analyses. No
      significant difference was seen in number of visits to the general practitioner
      at 12 months. CONCLUSIONS: The self management of arthritis programme reduced
      anxiety and improved participants' perceived self efficacy to manage symptoms,
      but it had no significant effect on pain, physical functioning, or contact with
      primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79115352
      [controlled-trials.com].

PMID- 17040927
TI  - Diabetes mellitus and infective endocarditis: the insulin factor in patient
      morbidity and mortality.
AB  - AIMS: To analyse the characteristics of infective endocarditis (IE) in patients
      with diabetes mellitus (DM), and to evaluate the prognostic significance of DM
      according to insulin use. METHODS AND RESULTS: A total of 559 patients with
      definite IE including 75 patients (13%) with DM (insulin use n = 22; oral
      antidiabetic n = 53) were evaluated. Comparison of insulin-DM, oral-DM, and non
      DM patients showed an older age (66 +/- 13, 66 +/- 10, 58 +/- 17, respectively; P
      = 0.004) in DM patients, and more frequent IE on prosthetic valves (32, 11, and
      15%, respectively; P = 0.068) in insulin-DM patients. Oral streptococci (0, 8,
      and 18%, respectively; P = 0.016) were less frequently the causative organism
      than staphylococci (64, 26, and 29%, respectively; P = 0.002) in insulin-DM
      patients. Vegetations, dehiscence, abscess, and regurgitation rates did not
      differ among the three groups, nor did cardiac surgery rates (32, 47, and 48%,
      respectively; P = 0.334), but in-hospital mortality was higher in insulin-DM
      patients (50, 19, and 15%; P < 0.001). In multivariable analysis, independently
      of other determinants of death (age, IE location, Staphylococcus aureus, history
      of heart failure, immunosuppression, creatinine serum), insulin-DM was a
      predictor of death (OR, 4.69; 95% CI, 1.77-12.44), whereas oral-DM was not.
      CONCLUSION: IE prognosis in insulin-DM patients is poor due to the coexistence of
      host and pathogen factors. Insulin-DM patients with IE may require specific
      management.

PMID- 17040928
TI  - The impact of anthropomorphic indices on clinical outcomes in patients with acute
      ST-elevation myocardial infarction.
AB  - AIMS: Multiple studies have focused on the relationship of body anthropometric
      measures with clinical events in ST-elevation myocardial infarction (STEMI)
      patients, highlighting the 'obesity paradox'. However, the relative prognostic
      importance of these measures over other baseline variables is less known. METHOD
      AND RESULTS: We performed a retrospective analysis of 94,108 STEMI patients from
      seven clinical trials evaluating various reperfusion strategies to study the
      relationship and prognostic importance of height, weight, body mass index (BMI),
      and body surface area (BSA) with 30-day death and in-hospital cardiogenic shock,
      major bleeding, and stroke. Main outcome measures of interest included 30-day
      death and in-hospital cardiogenic shock, major bleeding, and stroke. Weight, BMI,
      and BSA were inversely and independently related to all clinical events. Despite
      being statistically significant (P<0.0001), the prognostic information
      contributed by weight beyond that conferred by baseline clinical factors was
      minimal (<1% of total prognostic information) making it of limited clinical
      relevance for predicting 30-day death and cardiogenic shock. In contrast, weight
      accounted for 8.4% and 4.3% of the prognostic information in the logistic
      regression models for major bleeding and for stroke. BMI or BSA added little
      incremental value over simple measure of weight. CONCLUSION: Although
      statistically significantly related to most outcomes in patients with STEMI
      including death and shock, body weight provided clinically relevant prognostic
      information only for the risk of major bleeding and of stroke. Furthermore, BMI
      or BSA contributed little incremental prognostic information beyond that provided
      by weight alone. Thus, the existing large body of information concerning the
      strong prognostic importance of anthropometric measures with outcomes after STEMI
      should be interpreted in the context of other more important risk factors.

PMID- 17040929
TI  - Coronary plaque composition of culprit/target lesions according to the clinical
      presentation: a virtual histology intravascular ultrasound analysis.
AB  - AIMS: To evaluate the plaque composition obtained by virtual histology (VH) IVUS
      according to the clinical presentation and to compare those data to previously
      published histopathology data. METHODS AND RESULTS: VH was performed on 95 de
      novo significant lesions (>75% stenosis) in 85 patients [28 acute coronary
      syndrome (ACS) patients, 30 lesions; 57 stable angina pectoris (SAP) patients, 65
      lesions]. There were a higher prevalence of positive remodelling (47 vs. 22%,
      P=0.013), thrombus (20 vs. 1.5%, P=0.0037), and echo-lucent area (23.3 vs. 7.7%,
      P=0.047) in ACS patients. At the minimal lumen site, fibrous plaque area was
      significantly larger in ACS lesions than in SAP lesions (66.0+/-10.7 vs. 61.4+/
      8.9%, P=0.034), whereas necrotic core and dense calcium plaque area were smaller
      in ACS lesions (Necrotic core: 6.8+/-6.0 vs. 11.0+/-8.3%, P=0.02; Dense calcium:
      2.6+/-3.0 vs. 4.9+/-5.8%, P=0.03). No differences in rate of thin cap
      fibroatheroma, thick fibrotheroma, or for the presence of multiple necrotic core
      layers were observed between both groups. CONCLUSION: Plaque composition obtained
      by VH-IVUS shows less necrotic core and more fibrous tissue in ACS compared to
      SAP lesions, which is in contradiction with previously published histopathologic
      data.

PMID- 17040930
TI  - A modified back-etch method for preparation of plan-view high-resolution
      transmission electron microscopy samples.
AB  - A modified back-etch method is described that has been successfully used to
      prepare samples of thin films and nanoparticles on Si wafer substrates for
      examination by high-resolution transmission electron microscopy (HRTEM). This
      process includes ultrasonic cutting, abrasive pre-thinning and a two-stage
      etching procedure. Unlike previous reports of back-etching methods, tetramethyl
      ammonium hydroxide, which has a very high-etching selectivity of Si to SiO(2), is
      used for the final etching to allow removal of the Si without degradation of the
      SiO(2) membrane. An innovative wrapping method is also described. This novel
      approach reduces the preparation time for HRTEM samples to <1 h per sample for
      groups of 10 or more samples. As an example, the preparation of FePt nanoparticle
      samples for HRTEM imaging is described.

PMID- 17040931
TI  - The association of sequence variants in DNA repair and cell cycle genes with
      cancers of the upper aerodigestive tract.
AB  - Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity,
      pharynx, larynx and oesophagus, account for 5.2% of all cancers cases worldwide.
      The major risk factors, tobacco and alcohol can directly or indirectly generate
      DNA damage, which if unrepaired can give rise to mutations, unregulated cell
      growth and apoptosis induction. To clarify the role of DNA repair and cell cycle
      control proteins in UADT cancer susceptibility, we studied the risk in relation
      to 28 SNPs in 18 DNA repair enzymes and 9 SNPs in 7 cell cycle control genes. A
      case-control study was conducted from 2000 to 2002 in six centers from Romania,
      Poland, Russia, Slovakia and the Czech Republic. Patients diagnosed with squamous
      cell carcinoma of the UADT (n=811) and controls with a recent diagnosis of
      diseases unrelated to tobacco and alcohol (n=1083) were recruited. For UADT
      cancer risk, associations were observed for the homozygous carriers of the
      variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI)
      1.32-4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20-4.17) and OGG1 S326C (OR 2.07,
      95% CI 1.15-3.73) whilst three variants were associated with a protective effect
      (XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9
      200T > C, P for trend 0.009). Several other sequence variants showed associations
      with specific cancers without an overall association with UADT cancer. While some
      of these associations are consistent with previous studies, we cannot rule out
      the possibility of false-positive associations. The positive findings should be
      explored in another large-scale study on UADT cancers.

PMID- 17040932
TI  - Prevalence, diagnosis and relation to tobacco dependence of chronic obstructive
      pulmonary disease in a nationally representative population sample.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most
      common cause of death worldwide. It is caused primarily by cigarette smoking.
      Given its importance, it is remarkable that reliable national prevalence data are
      lacking for most countries. This study provides estimates of the national
      prevalence of COPD in England, the extent of under-detection of the disorder, and
      patterns of cigarette smoking, dependence, and motivation to stop smoking in
      those with the disease. METHODS: Data from 8215 adults over the age of 35 who
      participated in the Health Survey for England were analysed. Information was
      obtained on self-reported and cotinine validated smoking status, cigarette
      dependence, motivation to stop smoking, COPD defined by spirometry using joint
      American Thoracic Society and European Respiratory Society criteria, and self
      reports of diagnosis with respiratory disorders. RESULTS: Spirometry-defined COPD
      was present in 13.3% (95% CI 12.6 to 14.0) of participants, over 80% of whom
      reported no respiratory diagnosis. Even among people with severe or very severe
      COPD by spirometric assessment, only 46.8% (95% CI 39.1 to 54.6) reported any
      diagnosed respiratory disease. A total of 34.9% (95% CI 32.1 to 37.8) of people
      with spirometry-defined COPD were smokers compared with 22.4% (95% CI 21.4 to
      23.4) of those without, and smoking prevalence increased with disease severity.
      Smokers with spirometry-defined COPD were more cigarette dependent but had no
      greater desire to quit than other smokers. CONCLUSION: COPD is common among
      adults in England and is predominantly undiagnosed. In smokers it is associated
      with higher degrees of cigarette dependence but not with a greater motivation to
      stop smoking.

PMID- 17040933
TI  - Outcome of occupational asthma after cessation of exposure: a systematic review.
AB  - BACKGROUND: Patients with occupational asthma, and their medical advisers, need
      valid information about the prognosis of their disease. METHODS: A systematic
      review of the published literature on the symptomatic and functional outcomes of
      occupational asthma was carried out after avoidance of exposure to the causative
      agent. Through a full search of electronic and bibliographic sources, original
      studies documenting complete recovery from asthma (n = 39,1681 patients) or
      improvement in non-specific bronchial hyper-responsiveness (NSBHR; n = 28,695
      patients) were identified. The median duration of follow-up was 31 (range 6-240)
      months for studies of symptomatic recovery and 37 (6-240) months for studies of
      NSBHR. Most studies were of patients recruited from special clinics. RESULTS:
      Reported rates of symptomatic recovery varied from 0% to 100%, with a pooled
      estimate of 32% (95% CI 26% to 38%). These rates were lower with increasing age
      (p = 0.019) and among clinic based populations (p = 0.053). Patients with the
      shortest durations of exposure (< or =76 months) had the highest rate of recovery
      (36%; 95% CI 25% to 50%), but the effect was not linear. The pooled prevalence of
      persistent NSBHR at follow-up was 73% (95% CI 66% to 79%). This figure was higher
      among patients whose disease was due to high-molecular-weight agents (p = 0.006)
      and, less clearly, those from clinic-based populations (p = 0.561). In between
      study comparisons, no clear patterns of improvement relating to total duration of
      exposure or follow-up were found. From within-study comparisons there was some
      evidence that a shorter duration of symptoms was associated with a higher rate of
      symptomatic recovery. CONCLUSION: The available data on the prognosis of
      occupational asthma are insufficiently consistent to allow confident advice to be
      given to patients with the disease. Clinicians and epidemiologists with an
      interest in this disease should consider a collaborative and carefully
      standardised study of the prognosis of occupational asthma.

PMID- 17040934
TI  - Air travel in women with lymphangioleiomyomatosis.
AB  - BACKGROUND AND OBJECTIVE: The safety of air travel in patients with pneumothorax
      prone pulmonary diseases, such as lymphangioleiomyomatosis (LAM), has not been
      studied to any great extent. A questionnaire-based evaluation of air travel in
      patients with LAM was conducted to determine experiences aboard commercial
      aircraft. METHODS: A survey was sent to women listed in the US LAM Foundation
      registry (n = 389) and the UK LAM Action registry (n = 59) to assess air travel,
      including problems occurring during flight. Women reporting a pneumothorax in
      flight were followed up to ascertain further details about the incident. RESULTS:
      327 (73%) women completed the survey. 308 women answered the travel section, of
      whom 276 (90%) had "ever" travelled by aeroplane for a total of 454 flights. 95
      (35%) women had been advised by their doctor to avoid air travel. Adverse events
      reported included shortness of breath (14%), pneumothorax (2%, 8/10 confirmed by
      chest radiograph), nausea or dizziness (8%), chest pain (12%), unusual fatigue
      (11%), oxygen desaturation (8%), headache (9%), blue hands (2%), haemoptysis
      (0.4%) and anxiety (22%). 5 of 10 patients with pneumothorax had symptoms that
      began before the flight: 2 occurred during cruising altitude, 2 soon after
      landing and 1 not known. The main symptoms were severe chest pain and shortness
      of breath. DISCUSSION AND CONCLUSION: Adverse effects occurred during air travel
      in patients with LAM, particularly dyspnoea and chest pain. Hypoxaemia and
      pneumothorax were reported. The decision to travel should be individualised;
      patients with unexplained shortness of breath or chest pain before scheduled
      flights should not board. Patients with borderline oxygen saturations on the
      ground should be evaluated for supplemental oxygen therapy during flight.
      Although many women had been advised not to travel by air, most travelled without
      the occurrence of serious adverse effects.

PMID- 17040935
TI  - Does living near heavy industry cause lung cancer in women? A case-control study
      using life grid interviews.
AB  - BACKGROUND: The incidence of lung cancer among women is high in the highly
      industrialised area of Teesside in north-east England. Previous research has
      implicated industrial pollution as a possible cause. A study was undertaken to
      investigate whether prolonged residence close to heavy industry is associated
      with lung cancer among women in Teesside. METHODS: Two hundred and four women
      aged <80 years with incident primary lung cancer and 339 age matched community
      controls were recruited to a population based case-control study. Life course
      residential, occupational, and active and passive smoking histories were obtained
      using an interviewer administered questionnaire. RESULTS: The age adjusted odds
      ratio (OR) for lung cancer among people living >25 years v 0 years near (within 0
      5 km) heavy industry in Teesside was 2.13 (95% CI 1.34 to 3.38). After adjustment
      for confounding factors the OR was 1.83 (95% CI 0.82 to 4.08) for >25 years or
      1.10 (95% CI 0.96 to 1.26) for an additional 10 years living near industry. ORs
      were similar after residence near heavy industry outside Teesside was also
      included, and when latency was allowed for by disregarding residential exposures
      within the last 20 years. Adjustment for active smoking had the greatest effect
      on the OR. CONCLUSIONS: This population based study using life grid interviews
      for life course exposure assessment has addressed many deficiencies in the design
      of previous studies. The findings support those in most of the international
      literature of a modestly raised risk of lung cancer with prolonged residence
      close to heavy industry, although the confidence intervals were wide. The effect
      of air pollution on the incidence of lung cancer merits continued study.

PMID- 17040936
TI  - Asthma is associated with preterm birth but not with small for gestational age
      status among a population-based cohort of Medicaid-enrolled children <10 years of
      age.
AB  - BACKGROUND: Few population-based studies have evaluated the association between
      birth weight or gestation and subsequent clinically significant asthma. METHODS:
      Birth records of 37 349 Alaska residents <10 years of age who were enrolled in
      Medicaid for at least 365 days during 1999-2002 were linked to a Medicaid billing
      file. The occurrence of asthma and lower respiratory infections during the study
      period was categorised on the basis of standard International Classification of
      Diseases 9th Revision codes. The association between gestational age or small for
      gestational age status and asthma outcomes was adjusted for recent history of
      lower respiratory infection, years of Medicaid enrolment, age at enrolment and a
      variety of birth-related factors. RESULTS: Among children <5 years of age, the
      adjusted odds ratio (OR) for developing asthma decreased by 5.5% (95% confidence
      interval (CI) -0.2 to 10.9) and 7.9% (95% CI 5.2 to 10.4) per additional week of
      gestational age for children without and with any lower respiratory tract
      infection, respectively. For children > or =5 years of age, the adjusted OR for
      developing asthma decreased by 3.4% (95% CI -2.8 to 9.8) and 3.7% (95% CI -2.0 to
      9.2) per additional week of gestation for those without and with lower
      respiratory tract infection, respectively. Among all children with asthma, the
      adjusted OR for hospitalisation due to asthma decreased by 6.9% (95% CI 2.1 to
      11.5) for each additional week of gestational age. Small for gestational age
      status was not significantly associated with asthma outcomes. CONCLUSIONS:
      Preterm birth but not small for gestational age status predicted subsequent
      asthma outcomes. Adverse effects of preterm birth on asthma outcomes persist
      beyond age 5 years.

PMID- 17040937
TI  - Maternal effects on docility in Limousin cattle.
AB  - The objective of this study was to quantify the role of maternal effects on
      docility in Limousin cattle. Docility scores were obtained at weaning while
      animals were restrained in a squeeze chute. Scores 1 through 6 represented a
      docile to aggressive temperament, respectively, and were provided by the North
      American Limousin Foundation. Observations with unknown age of dam, contemporary
      groups containing less than 10 observations, contemporary groups with no
      variation, and single-sire contemporary groups were removed, leaving 21,932
      observations. A 2-generation pedigree file compiled from animals with
      observations contained 49,459 animals. Fixed effects were weaning contemporary
      group and age of dam (2, > or =3 yr). Six animal models encompassed combinations
      of random factors: direct genetic, maternal genetic, and maternal permanent
      environmental effects. The model D was the most basic, containing direct genetic
      and residual effects, and it resembled the method currently used by the North
      American Limousin Foundation for genetic evaluation of docility. Maternal genetic
      or permanent environmental effects were separately added to the model D, denoted
      as models DM and DC, respectively. Model DMC contained all random factors. Models
      DM-Zero and DMC-Zero were equivalent to models DM and DMC, respectively, but with
      zero direct-maternal genetic covariance. Direct heritability estimates were
      moderate for all models (0.29 +/- 0.02 to 0.38 +/- 0.03). Maternal heritability
      estimates were low, ranging from 0.01 +/- 0.01 (DM-Zero) to 0.05 +/- 0.02 (DM).
      Negative direct-maternal genetic correlations of -0.41 +/- 0.09 and -0.55 +/-
      0.09 were estimated for models DM and DMC, respectively. The proportion of
      phenotypic variance accounted for by maternal permanent environmental effects was
      0.03 +/- 0.01, 0.04 +/- 0.01, and 0.02 +/- 0.01 for models DC, DMC, and DMC-Zero,
      respectively. Likelihood ratio tests indicated that model DMC best fit the data.
      Although maternal genetic and maternal permanent environmental effects were
      significant, they accounted for only 8% (model DMC) of the phenotypic variance,
      and a Spearman rank correlation of 0.99 between models D and DMC showed sires did
      not rank differently with or without inclusion of these effects. Given these
      results, inclusion of maternal effects to the genetic evaluation of docility in
      Limousin cattle does not seem warranted.

PMID- 17040938
TI  - Analysis of litter size and days to lambing in the Ripollesa ewe. I. Comparison
      of models with linear and threshold approaches.
AB  - The analysis focused on model fitting of 2 ewe reproductive traits, litter size,
      and days to lambing (interval between the introduction of the ram into the flock
      and the subsequent parturition of the ewes). The experimental data set of the
      Universitat Autonoma of Barcelona flock was used, including 1,598 records of
      litter size and 1,699 records of days to lambing from 376 Ripollesa ewes between
      1986 and 2005. Univariate and bivariate models were considered as beginning
      points with linear or threshold approximation for litter size. Model fitting was
      evaluated in terms of goodness-of-fit and predictive ability, using the mean
      square error and the correlation between phenotypic and predicted records
      (rho(y,y)) as reference parameters. The bivariate model was preferable for both
      variables, minimizing mean square error and maximizing rho(y,y). A threshold
      approximation for litter size was preferable over a linear approximation. Models
      were also compared with a simulation study, comparing the correlation coefficient
      between simulated and predicted breeding values (rho(a,a)). The bivariate
      threshold model was favored, with a rho(y,y) of 0.677 and 0.834 for litter size
      and days to lambing, respectively. Correlation coefficients between simulated and
      predicted breeding values in the bivariate linear model were reduced slightly to
      0.651 and 0.831, respectively, and they were lowest with linear univariate models
      (0.642 and 0.802). Although the bivariate models for ewe litter size and days to
      lambing were more accurate than the univariate models, the threshold approaches
      showed a greater advantage under the bivariate model. For the purpose of genetic
      evaluation of litter size in sheep, use of the threshold-linear model seems
      justified. In the Ripollesa breed, the evaluation of litter size can benefit from
      recording birth weight.

PMID- 17040939
TI  - Effect of manganese supplementation and source on carcass traits, meat quality,
      and lipid oxidation in broilers.
AB  - An experiment was conducted using a total of 336 one-day-old, Arbor Acres
      commercial male broilers to investigate the effect of dietary Mn supplementation
      on carcass traits, meat quality, lipid oxidation, relative enzyme activities in
      abdominal fat and meat, and Mn-containing superoxide dismutase (MnSOD) mRNA level
      in meat. Broilers were randomly allotted by BW to 1 of 8 replicate cages (6
      chicks per cage) for each of 7 treatments in a completely randomized design
      involving a 2 x 3 factorial + 1 arrangement of treatments. Dietary treatments
      included the corn-soybean meal-based diet (control) and the basal diet
      supplemented with 100 or 200 mg of Mn/kg as MnSO(4) x H(2)O, Mn AA A with a
      chelation strength of 26.3 formation quotient (8.34% Mn), or Mn AA B with a
      chelation strength of 45.3 formation quotient (6.48% Mn). Birds fed supplemental
      Mn had lower (P < 0.10) percentages of abdominal fat, lipoprotein lipase (LPL),
      and malate dehydrogenase activities and greater (P < 0.07) hormone-sensitive
      lipase activities in abdominal fat than birds fed a control diet. Birds fed
      supplemental Mn from Mn AA A or Mn AA B had lower (P < 0.05) LPL activities in
      abdominal fat than those fed supplemental MnSO(4) x H(2)O. Birds fed supplemental
      Mn had lower (P < 0.03) malondialdehyde content in leg muscle and greater (P <
      0.02) MnSOD activities and MnSOD mRNA level in breast or leg muscle than those
      fed the control diet. Birds fed supplemental Mn from Mn AA A had a greater (P <
      0.02) MnSOD mRNA level in leg muscle than those fed supplemental MnSO(4) x H(2)O.
      Results from this study indicated that organic Mn was more available than
      inorganic Mn for decreasing LPL activity in abdominal fat of broilers, and
      dietary Mn might reduce abdominal adipose deposition by decreasing LPL and malate
      dehydrogenase activities or increasing hormone-sensitive lipase activity in
      abdominal adipose tissue. The results also indicated that dietary Mn upregulated
      muscle MnSOD gene expression pretranslationally in association with increased
      MnSOD activity, which might explain the decrease of malondialdehyde content in
      leg muscle.

PMID- 17040940
TI  - Could the pale, soft, and exudative condition be explained by distinctive
      histological characteristics?
AB  - Pork quality depends on various genetic and environmental factors. Despite the
      improvement of slaughter conditions, the PSE type is still one of the main
      concerns in this field. This study was conducted on nonstressed animals to
      evaluate the tissue characteristics of some muscles usually involved during
      stress compared with a reference muscle, the M. triceps brachii, which is
      actually not subject to stress-caused damages. Samples of M. triceps brachii, M.
      longissimus dorsi, M. biceps femoris, and M. semimembranosus were taken from pigs
      exhibiting 1 of the 3 HAL genotypes (NN, Nn, or nn) and 2 of the 3 RN genotypes
      (rn+rn+ or rn+RN-). Histoenzymology and immunohistochemistry were used to compare
      the fiber typing and capillary network in these muscles within these different
      stress susceptibility genotypes. In comparison with the reference muscle, M.
      triceps brachii, the combination of a high value of the number of type IIb fibers
      and a low vascular network showed a primary effect on muscles usually involved
      during stress. This led to the definition of a PSE index. A dramatic increase (P
      < 0.001) in this PSE index was systematically found in muscles usually involved
      in the PSE-type condition. These results show that distinctive histological
      characteristics were associated with the vulnerability of some muscles
      independently of the genotypes. Moreover, this study highlights the distinctive
      histological features of each genotype and is likely to suggest some interactions
      between them.

PMID- 17040941
TI  - Simulation of cow-calf production with and without realistic levels of
      variability.
AB  - The Colorado beef cattle production model, a whole-herd, individual-animal, life
      cycle simulation model, was used to determine if level of simulated variability
      affects simulation results. Beyond variability created by deterministic equations
      describing known biological relationships and direct input, the Colorado beef
      cattle production model can produce additional variation in a number of traits
      through its capacity to generate multinormal deviates for each animal. Runs
      simulating cow-calf production under ample and sparse levels of nutrition were
      performed with less than realistic and realistic levels of variability for mature
      weight, milk production, gestation length, maintenance requirements, appetite,
      and combinations thereof. Under poor nutrition, simulation with less than
      realistic variability altered means for pregnancy rate, postpartum interval, milk
      production, weaning weight, and mature weight by up to 14%, 8.6 d, 0.8 kg/d, 9.6
      kg, and 19.1 kg, respectively, in addition to changing the output for numerous
      other variables. The level of simulated variability affected the means of output
      variables through 2 mechanisms: (1) change in potentials due to differential
      culling, which can only take place if potentials are allowed to vary; and (2)
      further interaction with the model's nonlinear, deterministic equations. Our
      findings indicate that by not simulating realistic levels of variability, models
      with nonlinear functions may yield misleading results.

PMID- 17040942
TI  - Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small
      Tailed Han sheep (Ovis aries).
AB  - The Small Tailed Han is a prolific local sheep breed in China. The bone
      morphogenetic protein receptor IB (BMPR-IB) gene, which affects the fecundity of
      Booroola Merino sheep, and the bone morphogenetic protein 15 (BMP-15) gene, which
      affects the fecundity of Inverdale, Hanna, Belclare, Cambridge, and Lacaune
      sheep, were studied as candidate genes associated with the prolificacy of Small
      Tailed Han sheep. Single nucleotide polymorphisms of BMPR-IB and BMP-15 genes
      were detected in Small Tailed Han ewes (n = 188) by PCR-RFLP. The combined effect
      of the 2 genes on the prolificacy of Small Tailed Han sheep was studied. The
      results indicated that the same FecB mutation (Q249R) occurred in the BMPR-IB
      gene in Small Tailed Han ewes as found in Booroola Merino ewes. The Small Tailed
      Han ewes with genotypes FecB(B)/FecB(B) and FecB(B)/FecB(+) had 1.40 (P < 0.01)
      and 1.11 (P < 0.01) more lambs, respectively, than those with genotype
      FecB(+)/FecB(+). The same FecX(G) mutation (Q239Ter) of the BMP-15 gene was found
      in Small Tailed Han ewes as in Belclare and Cambridge ewes. The Small Tailed Han
      ewes with the heterozygous mutant FecX(G)/FecX(+) had 0.55 (P < 0.01) more lambs
      than those with the wild-type FecX(+)/FecX(+). The Small Tailed Han ewes carrying
      mutations in both BMPR-IB and BMP-15 genes had greater litter size than those
      with either mutation alone. In view of our results, marker-assisted selection
      using both BMPR-IB and BMP-15 genes is warranted to increase litter size in sheep
      and will be of considerable economic value to sheep producers.

PMID- 17040943
TI  - Lipid microencapsulation allows slow release of organic acids and natural
      identical flavors along the swine intestine.
AB  - The purpose of the present work was to investigate the in vivo concentrations of
      sorbic acid and vanillin as markers of the fate of organic acids (OA) and natural
      identical flavors (NIF) from a microencapsulated mixture and from the same
      mixture non-microencapsulated, and the possible consequences on the intestinal
      microbial fermentation. Fifteen weaned pigs were selected from 3 dietary groups
      and were slaughtered at 29.5 +/- 0.27 kg of BW. Diets were (1) control; (2)
      control supplemented with a blend of OA and NIF microencapsulated with
      hydrogenated vegetable lipids (protected blend, PB); and (3) control supplemented
      with the same blend of OA and NIF mixed with the same protective matrix in
      powdered form but without the active ingredient coating (non-protected blend,
      NPB). Stomach, cranial jejunum, caudal jejunum, ileum, cecum, and colon were
      sampled to determine the concentrations of sorbic acid and vanillin contained in
      the blend and used as tracers. Sorbic acid and vanillin were not detectable in
      pigs fed the control, and their concentrations were not different in the stomach
      of PB and NPB treatments. Pigs fed PB showed a gradual decrease of the tracer
      concentrations along the intestinal tract, whereas pigs fed NPB showed a decline
      of tracer concentration in the cranial jejunum and onwards, compared with the
      stomach concentrations. Sorbic acid and vanillin concentrations along the
      intestinal tract were greater (P = 0.02) in pigs fed PB compared with pigs fed
      NPB. Pigs fed PB had lower (P = 0.03) coliforms in the caudal jejunum and the
      cecum than pigs fed the control or NPB. Pigs fed the control or PB had a greater
      (P = 0.03) lactic acid bacteria plate count in the cecum than pigs fed NPB, which
      showed a reduction (P = 0.02) of lactic acid concentrations and greater (P =
      0.02) pH values in the caudal jejunum. The protective lipid matrix used for
      microencapsulation of the OA and NIF blend allowed slow-release of both active
      ingredients and prevented the immediate disappearance of such compounds upon
      exiting the stomach.

PMID- 17040944
TI  - Inbreeding trends and pedigree analysis of Irish dairy and beef cattle
      populations.
AB  - The objective of this study was to determine the inbreeding levels and to analyze
      the pedigree of Irish purebred populations of Charolais, Limousin, Hereford,
      Angus, and Simmental beef cattle, as well as the Holstein-Friesian dairy breed.
      Pedigree analyses included quantifying the depth of known pedigree, average
      generation intervals, effective population size, the effective number of
      founders, ancestors, and founder genomes, as well as identifying the most
      influential animals within the current population of each breed. The annual rate
      of increase in inbreeding over the past decade was 0.13% (P < 0.001) in the
      Hereford, 0.06% (P < 0.001) in the Simmental, and 0.10% (P < 0.001) in the
      Holstein-Friesian breeds. Inbreeding in the other breeds remained relatively
      constant over the past decade. Herefords had the greatest mean inbreeding in
      2004, at 2.19%, whereas Charolais had the lowest, at 0.54%. Over half of each
      purebred population in 2004 was inbred to some degree; the population with the
      greatest proportion of animals inbred was the Hereford breed (85%). All 6 breeds
      displayed a generation interval of approximately 6 yr in recent years. In the
      pure-bred females born in 2004, the 3 most influential animals contributed
      between 11% (Limousin) and 24% (Hereford) of the genes. Effective population size
      was estimated for the Hereford, Simmental, and Holstein-Friesian only, and was
      64, 127, and 75, respectively. The effective number of founders varied from 55
      (Simmental) to 357 (Charolais), whereas the effective number of ancestors varied
      from 35 (Simmental and Hereford) to 82 (Limousin). Thus, despite the majority of
      animals being inbred, the inbreeding level across breeds is low but rising at a
      slow rate in the Hereford, Simmental, and Holstein-Friesian.

PMID- 17040945
TI  - Variation in plasma growth hormone during first parity in lactating cows.
AB  - This study analyzed genetic and phenotypic variation in plasma GH during
      lactation in first parity dairy cows. The heritability and repeatability were
      examined using an algorithm for separation of basal and peak concentrations and
      different power transformations. Blood samples were obtained 17 times during
      first parity in 85 Holstein, 67 Red Dane, and 62 Jersey cows and assayed for GH.
      Each breed comprised 2 genetic groups; thus, a total of 6 genetic groups were
      defined. Across genetic groups, cows were assigned to 1 of 2 total mixed rations
      with a low or a normal energy concentration. The separation algorithm identified
      only 4.0% of the plasma GH concentrations as peaks. After excluding peak
      concentrations, the repeatability of GH during lactation was improved. A log
      transformation was found appropriate for GH. The log-transformed GH
      concentrations for lactating dairy cows had a heritability ranging between 0.14
      in early lactation to 0.08 in mid and late lactation. The repeatability was 0.24
      in early lactation and increased to between 0.58 and 0.61 in mid and late
      lactation. We conclude that for GH concentrations in lactating cows that are
      sampled infrequently, the exclusion of peak values to obtain a basal GH
      concentration was not effective in clarifying phenotypic or genetic effects.

PMID- 17040946
TI  - Development of computational models for the purpose of conducting individual
      livestock and premises traceback investigations utilizing National Animal
      Identification System-compliant data.
AB  - Many of the efforts surrounding the development of the National Animal
      Identification System have encompassed the identification of livestock production
      and handling premises as well as individuals or herds of animals, whereas little
      effort has been directed toward the ultimate goal of animal traceback within 48
      h. A mock data set representative of the Colorado cattle population was created
      for modeling of cattle traceability. Using this data set, algorithms were
      developed to complete rapid and accurate traceback and traceforward of animals or
      premises or both. On July 19, 2005, the Colorado Department of Public Health and
      Environment, in conjunction with the Colorado Department of Agriculture,
      conducted a test exercise pertaining to homeland security. The exercise team
      randomly identified animal number 926,583 (of the 2 million total animals) as a
      potentially infected animal of interest and requested a traceback of this animal.
      Traceback was accomplished in 215 s, and 540 primary coresident animals were
      identified. However, due to animal movements, the number of coresidents (animals
      exposed, directly or indirectly, to the animal of interest) expanded with
      coresidency level (level 1 = direct contact; level 2 = direct contact with an
      animal that had direct contact with the animal of interest; level 3 = direct
      contact with an animal that had contact with an animal that had direct contact
      with the animal of interest, etc.) to more than 1.2 million coresidents at level
      4, and more than 90% of all animals identified as a coresident at some level. In
      addition to the coresidency results, the premises containing the coresidents were
      identified and sorted by the number of coresidents. Because of animal movement,
      all 19,391 premises included in the data set had coresidents at some level. This
      exercise demonstrated the capability of the developed algorithms to complete
      rapid traceback and the complexity of the resulting animal traceback output.

PMID- 17040947
TI  - Associations of polymorphisms of the ovine prion protein gene with growth,
      carcass, and computerized tomography traits in Scottish Blackface lambs.
AB  - The objective of this study was to investigate and estimate the associations of
      the ovine prion protein (PrP) genotypes with a wide range of performance traits
      in Scottish Blackface lambs. Performance records of up to 7,138 sheep of known
      PrP genotypes born from 1999 to 2004 in 2 experimental farms were utilized.
      Performance traits studied were BW at birth, marking (when the sheep were
      identified with permanent ear tags at an average age of 52 d), and weaning
      (average age of 107 d); slaughter traits (BW at slaughter, slaughter age, carcass
      weight, and carcass conformation); ultrasonic muscle and fat depths; and
      computerized tomography-predicted carcass composition and carcass yield at
      weaning. Different linear mixed models, including random, direct animal effect,
      and up to 3 maternal effects (genetic, permanent, and temporary environmental)
      were used for the different traits. The PrP genotype was included in the model as
      a fixed effect, along with other fixed factors with significant effects (P <
      0.05). Five separate analyses were carried out for each trait, differing in the
      method of PrP genotypic classification. The first analysis was based on
      classifying the sheep into categories according to all 9 available PrP genotypes.
      In the other 4 analyses, sheep were categorized according to the number of each
      PrP allele carried. Results showed that there were no significant differences
      between PrP genotypes for any of the performance traits studied when all 9
      genotypes were compared (first analysis). Similarly, performance of the lambs did
      not significantly differ between genotypes with different numbers of ARR copies.
      However, there were significant variations in a few traits with respect to the
      number of ARQ, AHQ, and VRQ alleles carried. Heterozygous lambs for the AHQ or
      the ARQ allele were significantly heavier at some ages than lambs of the other
      genotypes. Lambs carrying the VRQ allele required approximately 10 d longer
      finishing time (P = 0.01) and yielded carcasses approximately 0.5 kg heavier (P =
      0.03) compared with noncarriers. The few significant associations found do not
      have a negative influence on performance when selecting against the most
      susceptible PrP allele (VRQ) or in favor of the most resistant one (ARR).
      Overall, there were no major associations of PrP genotypes with most lamb
      performance traits in Scottish Blackface sheep.

PMID- 17040948
TI  - Effects of crude red kidney bean lectin (phytohemagglutinin) exposure on
      performance, health, feeding behavior, and gut maturation of pigs at weaning.
AB  - The aim of this study was to obtain information that could help to ease the
      weaning transition in commercial pig production. Before weaning,
      phytohemagglutinin (PHA) in the form of a crude preparation of red kidney bean
      lectin was fed by gavage to 24 crossbred [(Swedish Landrace x Yorkshire) x
      Hampshire] piglets, whereas 24 control piglets were fed alpha-lactalbumin by
      gavage, to study the effect on growth, occurrence of postweaning diarrhea,
      feeding behavior, and some anatomical and physiological traits of the
      gastrointestinal tract. Within the litter, piglets were randomly assigned to PHA
      treatment or control and remained in the same pen from the beginning (PHA
      exposure at 7 d before weaning) until the end of the experiment (14 d post
      weaning). Weaning took place at the age of 31 to 34 d. Pigs treated with PHA grew
      faster (P = 0.013) during the first week postweaning and tended to have lower
      total diarrhea scores (P = 0.10) than did control pigs. On d 5 after weaning,
      piglets treated with PHA spent more time eating (P = 0.028) than control pigs. No
      immunostimulating effect of PHA, measured by plasma immunoglobulin G, could be
      detected. An increase in the intestinal barrier properties before weaning, as a
      response to PHA treatment, was demonstrated in intestinal absorption studies
      using Na-fluorescein and BSA as gavage-fed markers. Less uptake (measured as
      plasma concentrations) of the marker molecule Na-fluorescein occurred during a 24
      h study period, and numerically lower levels of BSA were observed compared with
      studies in control pigs of the same age. A total of 12 pigs (6 control, 6 PHA
      treated) were euthanized on the day of weaning for analyses of gastrointestinal
      properties. The PHA-treated pigs tended to have a longer total small intestinal
      length (P = 0.063) than that of the control pigs. The enzyme profile of the
      jejunal epithelium responded to PHA exposure with a decrease in lactase activity
      and an increase in maltase and sucrase activities, which is similar to changes
      normally observed after weaning. No differences were found in the size of the
      pancreas or in its contents of trypsin and amylase. In conclusion, exposing
      piglets to crude, red kidney bean lectin for 3 d during the week before weaning
      led to changes in performance and small intestinal functional properties that
      would be expected to contribute to a more successful weaning.

PMID- 17040949
TI  - Ribonucleic acid interference: a new approach to the in vivo study of gene
      function.
AB  - The definition of hormone function was classically accomplished by ablation
      replacement studies. However, as our knowledge of the complexity of hormones and
      growth factors has grown, it has become increasingly difficult to clearly define
      the necessity and function of many of the hormones, growth factors, and
      regulatory proteins under investigation. The use of homologous recombination
      within mouse embryonic stem cell lines allows functional gene ablation and has
      been used extensively during the past 15 yr to define specific gene function. The
      use of similar methodologies in livestock species has yet to yield an efficient
      approach. In contrast, the parallel development of our understanding of naturally
      occurring RNA interference, along with the development of efficient virus-based
      vectors for gene transfer, holds great potential for effectively "knocking down"
      specific gene function. Short-hairpin (sh) RNA-encoding cassettes, typically
      consisting of inverted repeats separated by a loop sequence and followed by a
      short poly(T) string to terminate transcription, are inserted downstream of an
      RNA polymerase III promoter within the viral vector of choice. Several viral
      vectors are useful for delivery of shRNA expression cassettes, each with
      particular attributes. Adenovirus- and lentivirus-derived vectors provide a high
      rate of infectivity in most mammalian cell types, with lentiviral vectors
      allowing stable integration into the host genome if the study of long-term
      effects is needed. Upon transcription, a shRNA is generated, and the loop is
      recognized by the processing enzyme Dicer, generating guide sequences. Guide
      sequences are incorporated into the RNA-induced silencing complex, which targets
      mRNA for degradation if recognized by the guide sequence. For each mRNA of
      interest, design and testing of a number of shRNA, along with adequate controls,
      are required to identify the most efficient construct before proceeding to in
      vivo use. This technology may become the method of choice for defining gene
      function in livestock.

PMID- 17040950
TI  - Regulation of meiotic maturation.
AB  - Mammalian oocytes are arrested at prophase of the first meiotic division before
      induction of maturation by the preovulatory LH surge. In vitro, oocyte maturation
      occurs spontaneously. The first meiotic arrest is characterized by a large
      nucleus called the germinal vesicle. One important signaling molecule for
      resumption of meiosis is cyclic AMP (cAMP). High levels of cAMP block spontaneous
      meiotic resumption. Research investigating the regulation of oocyte cAMP has led
      to the discovery of new receptors, guanosine 5'-triphosphate-binding (G)
      proteins, cyclases, and phosphodiesterases. Leydig insulin-like 3, a polypeptide
      growth factor of the insulin family, is expressed in thecal cells. Leydig insulin
      like 3 activates the Leu-rich, repeat-containing, G protein-coupled receptor 8,
      which is expressed in the oocyte. Coupled to the inhibitory GTP binding protein,
      this receptor leads to a decrease in cAMP production. Treatment with Leydig
      insulin-like 3 polypeptide initiates meiotic progression of oocytes in
      preovulatory follicles, demonstrating the importance of cAMP management for
      meiotic resumption. Furthermore, microinjection of an antibody against
      stimulatory G protein (Gs) into mouse oocytes results in meiotic resumption,
      suggesting that meiotic arrest of the oocyte is dependent on Gs activity. The
      orphan Gs-linked receptor, GPR3, is expressed in the oocyte. The oocytes of GPR3
      null mice resume meiosis when still in their follicles, suggesting that GPR3 is
      involved in the control of cAMP production and thus meiotic arrest. Cyclic
      nucleotides are synthesized by cyclases and degraded by phosphodiesterases. Mouse
      and rat oocytes express isoform 3 of adenylyl cyclase. In the mouse, the null
      mutation results in approximately 50% of the oocytes resuming meiosis,
      demonstrating the importance of the synthesis of cAMP in controlling nuclear
      maturation. The null mutation of the major phosphodiesterase expressed in mouse
      oocytes results in female sterility due to ovulation of meiotically arrested
      oocytes that cannot be fertilized. Maintenance of meiotic arrest is explained by
      constitutive cAMP signaling associated with undetectable cAMP-phosphodiesterase
      activity. Collectively, these results are beginning to illuminate the key
      signaling molecules involved in the control of intraoocyte cAMP levels, thus
      regulating the arrest and resumption of meiosis.

PMID- 17040951
TI  - Technical note: preorbital gland opening in red deer (Cervus elaphus) calves as
      an indicator of stress.
AB  - The opening of the preorbital gland of red deer (Cervus elaphus) calves has been
      previously associated with feeding and satiety. However, it has been suggested to
      be most likely affected by some other factor or factors, possibly by excitement
      of the calf. If so, a calf should open its preorbital gland while being exposed
      to any stressful procedure. The hypothesis was tested that the preorbital gland
      is closed in a relaxed calf, whereas it is opened in a stressed calf. Preorbital
      opening was observed in 41 newborn red deer farm calves during a regular daily
      routine consisting of a search for newborn calves, their inspection, weighing,
      and painful marking with an ear tag. The openness of the preorbital gland
      (preorbital gland closed or opened) was recorded just before manipulation of a
      lying calf (i.e., in a calm calf) and then during the manipulation (i.e., in a
      distressed calf). Before manipulation, in all but 3 calves (7.3%, all of which
      were males), the preorbital gland was closed. All calves observed (100%) opened
      their preorbital gland during their manipulation, at least by the time the ear
      was punctured by the ear tag. The proportion of individuals with an open gland
      was lower (P < 0.001) before than during manipulation (7.3 vs. 100%,
      respectively). Hence, openness of the preorbital gland in newborn red deer calves
      was associated with a stressful manipulation by the humans, which suggests that
      it may be a simple and easily recognized indicator of calf stress.

PMID- 17040952
TI  - Why is the fetal allograft not rejected?
AB  - In viviparous species, the conceptus must be protected from a potentially hostile
      maternal immune system. The major histocompatibility complex (MHC) is a genetic
      region that encodes MHC class I and class II proteins, which present peptide
      antigens to T lymphocytes and induce graft rejection. The MHC, class II proteins
      are only expressed on professional, antigen-presenting cells. However, classical,
      MHC class I proteins are expressed on all nucleated somatic cells. Protection of
      the conceptus from immune-mediated rejection involves downregulation of classical
      MHC class I antigen expression on trophoblast cells, which form the external
      epithelial layer of the placenta, and maintenance of an immunologically favorable
      immunosuppressive environment in the uterus. Normally, bovine trophoblast cells
      do not express MHC class I antigens before d 120 of pregnancy. However, during
      the last third of gestation, trophoblast cells in the inter-placentomal and
      arcade regions of the placenta express classical, MHC class I proteins, which
      could potentially induce fetal rejection, as well as nonclassical, MHC class I
      proteins. A human, nonclassical, MHC class I antigen, human leukocyte antigen G,
      is an important immunoregulatory factor required for the maintenance of
      pregnancy. In cattle, MHC class I expression during the last third of pregnancy
      has no adverse effects and probably contributes to placental separation at
      parturition. However, somatic cell nuclear transfer (SCNT) conceptuses, the
      majority of which are aborted between d 30 and 90 of pregnancy, had trophoblast
      cell expression of MHC class I antigens before d 34 of pregnancy. In conjunction
      with increased trophoblast MHC class I expression, SCNT pregnancies exhibited a
      marked increase in the number of stromal lymphocytes in the uteri of surrogate
      dams. A retrospective study found that SCNT pregnancies established using MHC
      class I-homozygous cell lines, in which the immunological barrier is greatly
      reduced, had significantly improved fetal survival from d 28 to term (51%
      survival for MHC-homozygous and 5% for MHC-heterozygous SCNT fetuses).
      Consequently, it appears that the high rate of fetal mortality in SCNT
      pregnancies is due, at least in part, to inappropriate expression of trophoblast,
      MHC class I antigens resulting in immune-mediated placental rejection. This
      suggests that appropriate regulation of MHC class I genes is critical for
      immunological acceptance of an allogeneic conceptus.

PMID- 17040953
TI  - Association of a single nucleotide polymorphism in SPP1 with growth traits and
      twinning in a cattle population selected for twinning rate.
AB  - Continued validation of genetic markers for economically important traits is
      crucial to establishing marker-assisted selection as a tool in the cattle
      industry. The objective of the current study was to evaluate the association of a
      SNP (T(9)/T(10)) in the osteopontin gene (SPP1) with growth rate in a large
      cattle population spanning multiple generations and representing alleles from 12
      founding breeds. This population has been maintained at the US Meat Animal
      Research Center since 1981 and subjected to selection for twinning rate.
      Phenotypic records for this population included twinning rate and ovulation rate,
      providing an opportunity to examine the potential effects of SPP1 genotype on
      reproductive traits. A set of 2,701 animals was geno-typed for the T(9)/T(10)
      polymorphism at SPP1. The geno-typic data, including previously genotyped markers
      on chromosome 6 (BTA6), were used in conjunction with pedigree information to
      estimate genotypic probabilities for all 14,714 animals with phenotypic records.
      The genotypic probabilities for females were used to calculate independent
      variables for regressions of additive, dominance, and imprinting effects.
      Genotypic regressions were fit as fixed effects in a mixed model analysis, in
      which each trait was analyzed in a 2-trait model where single births were treated
      as a separate trait from twin births. The association of the SPP1 marker with
      birth weight (P < 0.006), weaning weight (P < 0.007), and yearling weight (P <
      0.003) was consistent with the previously reported effects of SPP1 genotype on
      yearling weight. Our data supports the conclusion that the SNP successfully
      tracks functional alleles affecting growth in cattle. The previously undetected
      effect of the SNP on birth and weaning weight suggests this particular SPP1
      marker may explain a portion of the phenotypic variance explained by QTL for
      birth and HCW on BTA6.

PMID- 17040954
TI  - Online database for documenting clinical pathology resident education.
AB  - BACKGROUND: Training of clinical pathologists is evolving and must now address
      the 6 core competencies described by the Accreditation Council for Graduate
      Medical Education (ACGME), which include patient care. A substantial portion of
      the patient care performed by the clinical pathology resident takes place while
      the resident is on call for the laboratory, a practice that provides the resident
      with clinical experience and assists the laboratory in providing quality service
      to clinicians in the hospital and surrounding community. Documenting the
      educational value of these on-call experiences and providing evidence of
      competence is difficult for residency directors. An online database of these
      calls, entered by residents and reviewed by faculty, would provide a mechanism
      for documenting and improving the education of clinical pathology residents.
      METHODS: With Microsoft Access we developed an online database that uses active
      server pages and secure sockets layer encryption to document calls to the
      clinical pathology resident. Using the data collected, we evaluated the efficacy
      of 3 interventions aimed at improving resident education. RESULTS: The database
      facilitated the documentation of more than 4 700 calls in the first 21 months it
      was online, provided archived resident-generated data to assist in serving
      clients, and demonstrated that 2 interventions aimed at improving resident
      education were successful. CONCLUSIONS: We have developed a secure online
      database, accessible from any computer with Internet access, that can be used to
      easily document clinical pathology resident education and competency.

PMID- 17040955
TI  - Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio
      analysis in maternal plasma: Theoretical and empirical considerations.
AB  - BACKGROUND: The discovery of cell-free fetal DNA in maternal plasma has opened up
      new possibilities for noninvasive prenatal diagnosis. However, the use of
      maternal plasma fetal DNA for the direct detection of fetal chromosomal
      aneuploidies has not been reported. We postulate that the aneuploidy status of a
      fetus could be revealed by an epigenetic allelic ratio approach, i.e., by
      analyzing the allelic ratio of a single-base variation present within DNA
      molecules exhibiting a placental-specific epigenetic signature in maternal
      plasma. METHODS: Placental-derived fetal-specific unmethylated maspin (SERPINB5)
      promoter sequences on human chromosome 18 were detectable in placental-maternal
      DNA mixtures and in maternal plasma by bisulfite modification followed by
      methylation-specific PCR (MSP) and primer extension. The ratios between the
      extension products of the 2 alleles were calculated for heterozygous placentas,
      placental-maternal blood cell DNA mixtures, and maternal plasma samples. The
      allelic ratios were compared between pregnancies carrying trisomy 18 and euploid
      fetuses. RESULTS: The epigenetic allelic ratios of all tested trisomy 18 samples
      deviated from the reference range obtained from euploid samples (placental DNA,
      1.135 to 2.052; placental-maternal DNA mixtures, 1.170 to 1.985; maternal plasma,
      0.330 to 3.044; without skew correction on the raw mass spectrometric data). A
      theoretical model was established and validated that predicted that a minimum of
      200 copies of genomic DNA after bisulfite conversion were required for
      distinguishing euploid and aneuploid fetuses with confidence. CONCLUSION:
      Epigenetic allelic ratio analysis of maternal plasma DNA represents a promising
      approach for noninvasive prenatal diagnosis of fetal chromosomal aneuploidies.

PMID- 17040956
TI  - Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin
      resistance, and hyperglycemia in humans.
AB  - BACKGROUND: Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker
      for early detection of various renal injuries. Because lipocalin-2 is abundantly
      expressed in adipose tissue and liver, we investigated its relevance to obesity
      related pathologies. METHODS: We used real-time PCR and in-house immunoassays to
      quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db
      obese mice and their age- and sex-matched lean littermates. We analyzed the
      association between serum lipocalin-2 concentrations and various metabolic and
      inflammatory variables in 229 persons (121 men and 108 women) recruited from a
      previous cross-sectional study, and we evaluated the effect of the insulin
      sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic
      patients (21 men and 11 women). RESULTS: Compared with the lean littermates,
      lipocalin-2 mRNA expression in adipose tissue and liver and its circulating
      concentrations were significantly increased in db/db diabetic/obese mice (P
      <0.001). These changes were normalized after rosiglitazone treatment. In humans,
      circulating lipocalin-2 concentrations were positively correlated (P <0.005) with
      adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index,
      but negatively correlated (P = 0.002) with HDL cholesterol. There was also a
      strong positive association between lipocalin-2 concentrations and high
      sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity
      (P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2
      concentrations correlated significantly with increases in insulin sensitivity (r
      = 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P =
      0.003). CONCLUSIONS: Lipocalin-2 is an inflammatory marker closely related to
      obesity and its metabolic complications. Measurement of serum lipocalin-2 might
      be useful for evaluating the outcomes of various clinical interventions for
      obesity-related metabolic and cardiovascular diseases.

PMID- 17040957
TI  - Quantification of urinary oxalate by liquid chromatography-tandem mass
      spectrometry with online weak anion exchange chromatography.
AB  - BACKGROUND: Urinary oxalate is commonly measured with an enzymatic assay that is
      specific but requires a manual clean-up step to reduce ascorbic acid
      interference. We developed a urinary oxalate assay that uses liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with anion exchange
      chromatography and simple sample preparation. METHODS: We added calibrator or
      urine sample (10 microL) to 10 microL of (13)C2 oxalate and 400 microL of water
      and performed separation on a Waters OASIS WAX column, flow rate 0.6 mL/min, and
      then elution for 0.3 min with water containing 2 mmol/L ammonium acetate and 1
      mL/L formic acid and for 1.0 min with 750 mL/L methanol containing 20 mL/L
      ammonia. We detected multiple reaction monitoring transitions m/z 88.6 > 60.5 and
      m/z 90.5 > 61.5 for oxalic acid and 13C2-oxalate, respectively, with a Quattro
      micro tandem mass spectrometer in electrospray-negative mode. RESULTS: Oxalate
      and 13C2-oxalate eluted at 1.2 min. Mean recovery was 95%, limit of detection 3.0
      micromol/L, lower limit of quantification 100.0 micromol/L, linearity to 2212
      micromol/L, imprecision <6%, and bias <3% at 166, 880, and 1720 micromol/L.
      Oxalate eluted after the main area of ion suppression. Mean response ratios for
      urine and aqueous samples, enriched at 200 and 1000 micromol/L, were 3.7% and
      5.4%, respectively. No interference was observed from other organic acids.
      Passing and Bablock regression analysis comparing the Trinity Biotech enzymatic
      reagent set and LC-MS/MS showed LC-MS/MS = 1.06 (enzymatic assay) -21.2, r =
      0.964, n = 110. Bland Altman analysis showed general agreement, with a mean bias
      of -1.9 mumol/L. CONCLUSION: This LC-MS/MS assay is applicable for quantifying
      urinary oxalate excretion.

PMID- 17040958
TI  - Measurement of fibrosis marker xylosyltransferase I activity by HPLC electrospray
      ionization tandem mass spectrometry.
AB  - BACKGROUND: Xylosyltransferase I (XT-I), the key enzyme in the biosynthesis of
      glycosaminoglycan chains in proteoglycans, has increased activity in the blood
      serum of patients with connective tissue diseases. Therefore, the measurement of
      serum XT-I activity is useful to monitor disease activity in these patients.
      METHODS: We developed an HPLC electrospray ionization tandem mass spectrometry
      method to assay XT-I activity in serum by use of a synthetic peptide (Bio-BIK-F)
      as the XT-I substrate. On the basis of XT-I-mediated transfer of D-xylose from
      UDP-D-xylose to the synthetic peptide to form Bio-BIK-F-Xyl, we determined XT-I
      activity in human serum samples. RESULTS: Multiple calibration curves for the
      analysis of Bio-BIK-F-Xyl exhibited consistent linearity and reproducibility in
      the range of 0.20-20 mg/L, corresponding to XT-I activity of 1.14-114 mU/L under
      assay conditions. The mean (SD, range) XT-I activity values in 30 blood donor
      sera were 18.4 (3.0, 8.7-24.8) mU/L. The limit of detection and lower limit of
      quantification were 8.5 microg/L (0.05 mU/L) and 163 microg/L Bio-BIK-F-Xyl (0.93
      mU/L XT-I activity), respectively. Interassay imprecision (CV) was 5.4%-26.1% in
      the range of 0.64 to 129 mU/L, and mean recovery was 107% (range, 96%-129%).
      Method comparison with the radiochemical assay showed a moderate correlation (r =
      0.79). The Passing-Bablok regression line was: radiochemical assay = 0.045 LC
      MS/MS + 0.061 mU/L, S(y/x) = 0.186. CONCLUSIONS: This simple and robust LC-MS/MS
      assay permits the rapid and accurate determination of XT-I activity in human
      serum.

PMID- 17040959
TI  - Quantitative assay of deletion or duplication genotype by capillary
      electrophoresis system: Application in Prader-Willi syndrome and Duchenne
      muscular dystrophy.
AB  - BACKGROUND: Deletions and duplications involving large DNA segments result in
      underexpression or overexpression, depending on the changes in allele dose, and
      are known to cause many common disorders. Detection of allele dose variations in
      the human genome is increasingly important in medical genetic diagnosis. METHODS:
      We used multiplex quantitative PCR coupled with capillary electrophoresis for
      accurate allele dose determination. In cases of Prader-Willi syndrome (PWS), a
      total of 24 patients with PWS, as well as 205 control individuals from the
      general population, were analyzed by use of multiplex quantitative PCR to amplify
      the FGFR2 gene, the KRIT1 gene, and the SNRPN gene simultaneously. In cases of
      Duchenne muscular dystrophy (DMD), we optimized the multiplex quantitative PCR to
      amplify 38 exons to analyze the DMD gene for rapid diagnosis of 12 DMD-affected
      males, 12 obligate carriers from families, and 50 unaffected female controls.
      RESULTS: We were able to unambiguously diagnose the deletion genotype in PWS
      patients and identify all deletion or duplication genotypes and carrier status in
      DMD-affected cases with 100% sensitivity and specificity. CONCLUSIONS: This
      report describes a novel single assay that can rapidly quantify allele dose to
      provide accurate clinical genetic diagnosis. This technique offers a valuable
      alternative for the rapid detection of genomic deletions or duplications and
      decreases costs because it does not require expensive fluorescent reagents.

PMID- 17040960
TI  - Sensitive detection of KIT D816V in patients with mastocytosis.
AB  - BACKGROUND: The 2447 A > T pathogenic variation at codon 816 of exon 17 (D816V)
      in the KIT gene, occurring in systemic mastocytosis (SM), leads to constitutive
      activation of tyrosine kinase activity and confers resistance to the tyrosine
      kinase inhibitor imatinib mesylate. Thus detection of this variation in SM
      patients is important for determining treatment strategy, but because the
      population of malignant cells carrying this variation is often small relative to
      the normal cell population, standard molecular detection methods can be
      unsuccessful. METHODS: We developed 2 methods for detection of KIT D816V in SM
      patients. The first uses enriched sequencing of mutant alleles (ESMA) after BsmAI
      restriction enzyme digestion, and the second uses an allele-specific competitive
      blocker PCR (ACB-PCR) assay. We used these methods to assess 26 patients
      undergoing evaluation for SM, 13 of whom had SM meeting WHO classification
      criteria (before variation testing), and we compared the results with those
      obtained by direct sequencing. RESULTS: The sensitivities of the ESMA and the ACB
      PCR assays were 1% and 0.1%, respectively. According to the ACB-PCR assay
      results, 65% (17/26) of patients were positive for D816V. Of the 17 positive
      cases, only 23.5% (4/17) were detected by direct sequencing. ESMA detected 2
      additional exon 17 pathogenic variations, D816Y and D816N, but detected only 12
      (70.5%) of the 17 D816V-positive cases. Overall, 100% (15/15) of the WHO
      classified SM cases were codon 816 pathogenic variation positive. CONCLUSION:
      These findings demonstrate that the ACB-PCR assay combined with ESMA is a rapid
      and highly sensitive approach for detection of KIT D816V in SM patients.

PMID- 17040961
TI  - Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum.
AB  - BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated
      links between obesity and insulin resistance in rodents. In humans,
      proinflammatory properties of resistin are superior to its insulin resistance
      inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues,
      serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis
      and spondylarthropathies (SpA), and to study its relationship with inflammatory
      status and rheumatoid arthritis disease activity. METHODS: Resistin expression
      and localisation in synovial tissue was determined by immunohistochemistry and
      confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin
      (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant
      protein-1 levels were measured. The clinical activity of patients with rheumatoid
      arthritis was assessed according to the 28 joint count Disease Activity Score
      (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid
      arthritis and osteoarthritis. Staining in the sublining layer was more intensive
      in patients with rheumatoid arthritis compared with those with osteoarthritis. In
      rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells
      (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial
      fluid resistin was higher in patients with rheumatoid arthritis than in those
      with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis
      and SpA, serum resistin levels were higher than those with osteoarthritis
      (p<0.01). Increased serum resistin in patients with rheumatoid arthritis
      correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not
      with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local
      sites of inflammation and the link between serum resistin, inflammation and
      disease activity suggest a role for resistin in the pathogenesis of rheumatoid
      arthritis.

PMID- 17040962
TI  - High anti-collagen type-II antibody levels and induction of proinflammatory
      cytokines by anti-collagen antibody-containing immune complexes in vitro
      characterise a distinct rheumatoid arthritis phenotype associated with acute
      inflammation at the time of disease onset.
AB  - OBJECTIVE: To investigate whether the cytokine-inducing properties of surface
      bound collagen type II (CII)-containing immune complexes (IC), which were
      reported earlier, have any clinical impact. METHODS: Anti-CII serology was
      analysed in 274 patients with early rheumatoid arthritis (RA). Patients with
      increased levels of anti-CII were followed serially for 1-5 years with regard to
      anti-CII IC-induced levels of tumour necrosis factor (TNF)alpha, interleukin
      (IL)1beta and IL8. Levels of antibodies and IC-induced cytokines were compared
      with clinical indices over 5 years of follow-up. RESULTS: 5/100 healthy controls
      and 24/274 (8.8%) patients with RA exhibited increased levels (>29 arbitrary
      units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274
      (3.3%) patients with RA and no controls comprised a discrete group with high anti
      CII levels>450 AU/ml. These high anti-CII level sera were associated with
      induction of pro-inflammatory cytokines by anti-CII-containing IC formed in
      vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel
      decline in antibody levels, IC-induced cytokines, C reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had
      significantly increased levels of CRP and ESR at baseline, but not later during
      the follow-up. CONCLUSIONS: Anti-native CII-positive patients with RA have a
      distinct clinical phenotype characterised by an early acute phase response that
      might be driven by anti-CII-containing IC in joint cartilage.

PMID- 17040963
TI  - Increase of B cell-activating factor of the TNF family (BAFF) after rituximab
      treatment: insights into a new regulating system of BAFF production.
AB  - BACKGROUND: The cytokine B cell-activating factor of the TNF family (BAFF) is
      involved in the pathogenesis of autoimmune diseases. OBJECTIVE: To access changes
      in serum protein and mRNA levels of BAFF after rituximab treatment. METHODS:
      Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five
      patients (two with lupus, two with Sjogren's syndrome, one with rheumatoid
      arthritis) before and 12 weeks (range 7-17) after a first course of rituximab
      infusion. Monocytes and B cells were selected from healthy controls and
      cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real
      time PCR, respectively. RESULTS: After rituximab treatment, median serum BAFF
      protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In
      monocytes cocultured with autologous B cells, BAFF protein level decreased,
      whereas the mRNA level was stable. In one closely monitored patient, the mRNA
      ratio of BAFF to actin in PBMCs increased later than the BAFF serum level.
      CONCLUSIONS: Two distinct mechanisms are probably involved in the increase in
      BAFF level after B cell depletion: (1) the decrease in its receptors leading to a
      release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could
      favour the re-emergence of autoreactive B cells.

PMID- 17040964
TI  - Insulin-like growth factor-I receptors in atherosclerotic plaques of symptomatic
      and asymptomatic patients with carotid stenosis: effect of IL-12 and IFN-gamma.
AB  - The balance between apoptosis and survival of vascular smooth muscle cells
      (VSMCs) in the fibrous cap appears to best correlate with plaque instability or
      stability and is controlled by growth factors and cytokines. We recently reported
      the inhibition of insulin-like growth factor (IGF)-I-induced proliferation and
      increase in apoptosis of VSMCs by atheroma-associated cytokines. Here we assessed
      the expression of IGF-I receptor (IGF-IR) in atherosclerotic plaques and in
      plaque VSMCs of asymptomatic and symptomatic patients with carotid stenosis and
      examined the effect of IGF-I, IL-12, and IFN-gamma on the expression of IGF-IR
      and IGF-binding protein (IGFBP)-3 in plaque VSMCs. We observed significantly
      lower density of terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling-positive apoptotic nuclei and increased positive immunoreactivity to IGF
      IR and mRNA transcripts of endogenous IGF-I and IGF-IR in asymptomatic than in
      symptomatic plaque VSMCs. Positive correlation was found between apoptosis and
      IGF-IR expression in asymptomatic (r(2) = 0.942) and symptomatic (r(2) = 0.908)
      plaque VSMCs. The specific binding of (125)I-labeled IGF-I was 3.7-fold higher in
      plaque VSMCs of asymptomatic patients than in symptomatic patients. IGF-I
      increased both IGF-IR mRNA transcripts and expression of IGFBP-3 in VSMCs of
      asymptomatic plaques. IL-12 and IFN-gamma decreased IGF-IR mRNA transcripts and
      further increased the expression of IGFBP-3 in asymptomatic VSMCs but had no
      effect in symptomatic VSMCs. These data suggest that the decreased expression of
      IGF-IR mRNA and increased expression of IGFBP-3 in carotid plaques of symptomatic
      patients could be due to atheroma-associated cytokines and this could result in
      plaque instability.

PMID- 17040965
TI  - Kv1.5 is a major component underlying the A-type potassium current in retinal
      arteriolar smooth muscle.
AB  - Little is known about the molecular characteristics of the voltage-activated K(+)
      (K(v)) channels that underlie the A-type K(+) current in vascular smooth muscle
      cells of the systemic circulation. We investigated the molecular identity of the
      A-type K(+) current in retinal arteriolar myocytes using patch-clamp techniques,
      RT-PCR, immunohistochemistry, and neutralizing antibody studies. The A-type K(+)
      current was resistant to the actions of specific inhibitors for K(v)3 and K(v)4
      channels but was blocked by the K(v)1 antagonist correolide. No effects were
      observed with pharmacological agents against K(v)1.1/2/3/6 and 7 channels, but
      the current was partially blocked by riluzole, a K(v)1.4 and K(v)1.5 inhibitor.
      The current was not altered by the removal of extracellular K(+) but was
      abolished by flecainide, indicative of K(v)1.5 rather than K(v)1.4 channels.
      Transcripts encoding K(v)1.5 and not K(v)1.4 were identified in freshly isolated
      retinal arterioles. Immunofluorescence labeling confirmed a lack of K(v)1.4
      expression and revealed K(v)1.5 to be localized to the plasma membrane of the
      arteriolar smooth muscle cells. Anti-K(v)1.5 antibody applied intracellularly
      inhibited the A-type K(+) current, whereas anti-K(v)1.4 antibody had no effect.
      Co-expression of K(v)1.5 with K(v)beta1 or K(v)beta3 accessory subunits is known
      to transform K(v)1.5 currents from delayed rectifers into A-type currents.
      K(v)beta1 mRNA expression was detected in retinal arterioles, but K(v)beta3 was
      not observed. K(v)beta1 immunofluorescence was detected on the plasma membrane of
      retinal arteriolar myocytes. The findings of this study suggest that K(v)1.5,
      most likely co-assembled with K(v)beta1 subunits, comprises a major component
      underlying the A-type K(+) current in retinal arteriolar smooth muscle cells.

PMID- 17040966
TI  - Heart slice NMR.
AB  - Nuclear magnetic resonance (NMR) spectroscopy of the heart is normally carried
      out using whole heart preparations under coronary perfusion. In such
      preparations, either radical changes in ionic composition of the perfusate or
      applications of numerous drugs would affect coronary microcirculation. This
      report communicates the first (31)P NMR spectroscopy study using a heart slice
      preparation (left ventricular slices) superfused with extracellular medium. The
      ratio of phosphocreatine concentration to ATP concentration was approximately
      2.1. Also, intracellular pH and Mg(2+) concentration ([Mg(2+)](i)), estimated
      from the chemical shifts of inorganic phosphate and ATP, were comparable with
      those under retrograde perfusion. [Mg(2+)](i) was significantly increased by the
      removal of extracellular Na(+), supporting the essential role of Na(+)-coupled
      Mg(2+) transport in Mg(2+) homeostasis of the heart. Heart slice preparation
      could also be used to evaluate the potency of cardiac drugs, regardless of their
      possible effects on coronary microcirculation.

PMID- 17040967
TI  - The mechanism of flow-induced dilation in human adipose arterioles involves
      hydrogen peroxide during CAD.
AB  - Flow-induced dilation (FID) is an important physiological stimulus that regulates
      tissue blood flow and is mediated by endothelium-derived factors that play a role
      in vascular integrity and the development of atherosclerosis. In coronary artery
      disease (CAD), conduit artery FID is impaired. The purpose of this study was to
      determine the mechanism of FID in human visceral adipose and examine whether the
      presence of conduit coronary atherosclerosis is associated with altered
      endothelial function in visceral fat. FID was determined in isolated visceral fat
      arterioles from patients with and without CAD. After constriction with endothelin
      1, increases in flow produced an endothelium-dependent vasodilation that was
      sensitive to N(omega)-nitro-l-arginine methyl ester (l-NAME) in visceral fat
      arterioles from patients without CAD. In contrast, l-NAME alone or in combination
      with indomethacin had no effect on FID in similarly located arterioles from
      patients with CAD. Flow increased dichlorofluorescein (DCF) and dihydroethidium
      fluorescence accumulation in arterioles from patients with CAD versus without,
      indicative of the production of oxidative metabolites and superoxide,
      respectively. Both the dilation and DCF fluorescence to flow were reduced in the
      presence of the H(2)O(2) scavenger polyethylene glycol-catalase. Exogenous
      H(2)O(2) elicited similar relaxations of arterioles from patients in both groups.
      These data indicate that FID in visceral fat arterioles is nitric oxide dependent
      in the absence of known CAD. However, in the presence of CAD, H(2)O(2) replaces
      nitric oxide as the mediator of endothelium-dependent FID. This study provides
      evidence that adverse microvascular changes during CAD are evident in human
      visceral adipose, a tissue associated with CAD.

PMID- 17040968
TI  - Surface association of pregnancy-associated plasma protein-A accounts for its
      colocalization with activated macrophages.
AB  - Intense immunostaining for pregnancy-associated plasma protein-A (PAPP-A), a
      newly characterized metalloproteinase in the insulin-like growth factor system,
      colocalizes with activated macrophages in human atherosclerotic plaque. To
      determine macrophage regulation of PAPP-A expression, we developed two models of
      human macrophages with basal and activated phenotypes. THP-1 cells and peripheral
      blood monocytes could be differentiated into macrophages and activated upon
      specific treatment regimens with phorbol myristate acetate, macrophage colony
      stimulating factor, and interleukin-1beta. Activation was assessed by cell
      secretion of tumor necrosis factor-alpha, which increased 30- to 100-fold with
      activation. Activated macrophages also secreted matrix metalloproteinase-9.
      However, no PAPP-A mRNA or PAPP-A antigen could be detected in these cells under
      any condition. Upon incubation with recombinant PAPP-A, we found that activated
      macrophages bound and internalized more PAPP-A than unactivated macrophages or
      monocytes. Internalization accounted for at least 50% of macrophage-associated
      PAPP-A, as assessed in studies with cytochalasin B. Membrane-bound PAPP-A
      retained protease activity, whereas internalized PAPP-A had little or no
      activity. Similar experiments carried out with a mutated variant of PAPP-A, which
      retains functionality as a protease but is unable to bind surface-associated
      glycosaminoglycan, showed no macrophage association or internalization. Absence
      of PAPP-A expression was confirmed in activated macrophages isolated from a
      hypercholesterolemic rabbit model of atherosclerosis. We therefore conclude that
      PAPP-A is not synthesized in, but rather is bound and internalized by,
      macrophages. Our findings likely account for the observed intense immunostaining
      for PAPP-A colocalizing with activated macrophages and may have physiological
      significance in the development of vulnerable plaque.

PMID- 17040969
TI  - Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in
      arachidonic acid-induced relaxation.
AB  - Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either
      nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX)
      and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15
      trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic
      acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis
      that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate
      limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic
      endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA
      (Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction
      increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected
      by immunoblotting with an anti-human15-LO-1 antibody, and increased the
      production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad
      15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial
      cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7
      +/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control
      nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1
      treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a
      cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is
      sufficient to increase the production of the vasodilatory HEETA and THETA and
      enhance the relaxations to AA. This confirms the role of HEETA and THETA as
      endothelium-derived relaxing factors.

PMID- 17040970
TI  - Extracellular glycerol regulates the cardiac energy balance in a working rat
      heart model.
AB  - We reported previously that glycerol is a substrate for energy production in
      cardiomyocytes. Increasing glycerol availability results in increased glycerol
      uptake and its involvement in complex lipid biosynthesis and energy production.
      This study evaluated the relationship between glycerol supply, energy demand, and
      intermediary metabolism leading to energy production. The work was performed on
      isolated rat heart perfused in the working mode. Glycerol concentrations modeled
      the fasting (0.33 mM) and fed (3.33 mM) states. Cardiac energy demand was modeled
      by increasing heart rate from 350 to 450 beats/min (bpm). Increasing glycerol
      supply increased glycerol uptake from 1.4 (350 bpm) to 3.8 (450 bpm) and from 9.7
      (350 bpm) to 34.2 (450 bpm) micro mol glycerol/heart in 30 min at 0.33 and 3.33
      mM glycerol, respectively. At low glycerol supply, increasing heart rate did not
      influence the complex lipid synthesis. Conversely, high glycerol concentration
      increased the complex lipid synthesis by 5- and 30-fold at 350 and 450 bpm,
      respectively. Increasing glycerol supply and heart rate significantly increased
      glycerol oxidation rate. Moreover, increasing glycerol supply did not affect
      glucose oxidation but increased palmitate uptake and significantly decreased its
      beta-oxidation. Physiological concentrations of glycerol contribute to the
      cardiac intermediary metabolism, both for energy production and glycerolipid
      synthesis. Increasing energy demand enhances the requirement and use of glycerol.
      Glycerol contributes to the regulation of cardiac metabolism and energy balance,
      mainly by decreasing the contribution of fatty acid oxidation, and may thus
      represent a new factor in cardiac protection through the reduction of oxygen
      demand.

PMID- 17040971
TI  - Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role
      of p38 MAPK.
AB  - It is generally believed that a mechanical signal initiates a cascade of
      biological events leading to coordinated cardiac remodeling. 14-3-3 family
      members are dimeric phosphoserine-binding proteins that regulate signal
      transduction, apoptotic, and checkpoint control pathways. To evaluate the
      molecular mechanism underlying swimming stress-induced cardiac remodeling, we
      examined the role of 14-3-3 protein and MAPK pathway by pharmacological and
      genetic means using transgenic mice with cardiac-specific expression of dominant
      negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38alpha/beta MAPK (DNp38alpha
      and DNp38beta) mice. p38 MAPK activation was earlier, more marked, and longer in
      the myocardium of the TG group compared with that of the nontransgenic (NTG)
      group after swimming stress, whereas JNK activation was detected on day 5 and
      decreased afterward. In contrast, ERK1/2 was not activated after swimming stress
      in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were
      greatly increased in the TG group compared with those in the NTG group. Moreover,
      we found a significant correlation between p38 MAPK activation and apoptosis in
      the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic
      peptide expression. In contrast, DNp38alpha and DNp38beta mice exhibited reduced
      mortality and increased resistance to cardiac remodeling after 28 days of
      swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK
      inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis
      and improvement in the survival rate in the TG group. These results indicate for
      the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in
      left ventricular remodeling associated with swimming stress.

PMID- 17040972
TI  - P2X purinergic receptor-mediated ionic current in cardiac myocytes of
      calsequestrin model of cardiomyopathy: implications for the treatment of heart
      failure.
AB  - P2X purinergic receptors, activated by extracellular ATP, mediate a number of
      cardiac cellular effects and may be important under pathophysiological
      conditions. The objective of the present study was to characterize the P2X
      receptor-mediated ionic current and determine its role in heart failure using the
      calsequestrin (CSQ) model of cardiomyopathy. Membrane currents under voltage
      clamp were determined in myocytes from both wild-type (WT) and CSQ mice. The P2X
      agonist 2-methylthio-ATP (2-meSATP) induced an inward current that was greater in
      magnitude in CSQ than in WT ventricular cells. The novel agonist, MRS-2339, an N
      methanocarba derivative of 2-chloro-AMP relatively resistant to nucleotidase,
      induced a current in the CSQ myocyte similar to that by 2-meSATP. When
      administered via a miniosmotic pump (Alzet), it significantly increased longevity
      compared with vehicle-injected mice (log rank test, P = 0.02). The improvement in
      survival was associated with decreases in the heart weight-to-body weight ratio
      and in cardiac myocyte cross-sectional area [MRS-2339-treated mice: 281 +/- 15.4
      (SE) mum(2), n = 6 mice vs. vehicle-treated mice: 358 +/- 27.8 mum(2), n = 6
      mice, P < 0.05]. MRS-2339 had no vasodilator effect in mouse aorta ring
      preparations, indicating that its salutary effect in heart failure is not because
      of any vascular unloading. The cardiac P2X current is upregulated in the CSQ
      heart failure myocytes. Chronic administration of a nucleotidase-resistant
      agonist confers a beneficial effect in the CSQ model of heart failure, apparently
      via an activation of the cardiac P2X receptor. Cardiac P2X receptors represent a
      novel and potentially important therapeutic target for the treatment of heart
      failure.

PMID- 17040973
TI  - Immune suppression prevents renal damage and dysfunction and reduces arterial
      pressure in salt-sensitive hypertension.
AB  - The goal of this study was to test the hypothesis that renal infiltration of
      immune cells in Dahl S rats on increased dietary sodium intake contributes to the
      progression of renal damage, decreases in renal hemodynamics, and development of
      hypertension. We specifically studied whether anti-immune therapy, using
      mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB
      activation, renal infiltration of monocytes/macrophages, renal damage, decreases
      in glomerular filtration rate (GFR) and renal plasma flow, and increases in
      arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were
      maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na +
      MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day
      35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal
      NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF
      treatment significantly decreased renal monocyte/macrophage infiltration and
      renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean
      arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial
      pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake,
      treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage
      infiltration and improves renal function, lessens renal injury, and decreases
      arterial pressure. This suggests that renal infiltration of immune cells is
      associated with increased arterial pressure and renal damage and decreasing GFR
      and renal plasma flow in Dahl salt-sensitive hypertension.

PMID- 17040975
TI  - Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats
      with chronic heart failure.
AB  - Intrinsic muscle abnormalities affecting skeletal muscle are often reported
      during chronic heart failure (CHF). Because myosin is the molecular motor of
      force generation, we sought to determine whether its dysfunction contributes to
      skeletal muscle weakness in CHF and, if so, to identify the underlying causative
      factors. Severe CHF was induced in rats by aortic stenosis. In diaphragm and
      soleus muscles, we investigated in vitro mechanical performance, myosin-based
      actin filament motility, myosin heavy (MHC) and light (MLC) chain isoform
      compositions, MLC integrity, caspase-3 activation, and oxidative damage.
      Diaphragm and soleus muscles from CHF exhibited depressed mechanical performance.
      Myosin sliding velocities were 16 and 20% slower in CHF than in sham in diaphragm
      (1.9 +/- 0.1 vs. 1.6 +/- 0.1 microm/s) and soleus (0.6 +/- 0.1 vs. 0.5 +/- 0.1
      microm/s), respectively (each P < 0.05). The ratio of slow-to-fast myosin isoform
      did not differ between sham and CHF. Immunoblots with anti-MLC antibodies did not
      detect the presence of protein fragments, and no activation of caspase-3 was
      evidenced. Immunolabeling revealed oxidative damage in CHF muscles, and MHC was
      the main oxidized protein. Lipid peroxidation and expression of oxidized MHC were
      significantly higher in CHF than in shams. In vitro myosin exposure to increasing
      ONOO(-) concentrations was associated with an increasing amount of oxidized MHC
      and a reduced myosin velocity. These data provide experimental evidence that
      intrinsic myosin dysfunction occurs in CHF and may be related to oxidative damage
      to myosin.

PMID- 17040974
TI  - Circulating levels of cytochrome c after resuscitation from cardiac arrest: a
      marker of mitochondrial injury and predictor of survival.
AB  - Ca(2+) overload and reactive oxygen species can injure mitochondria during
      ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during
      cardiac resuscitation, causing release of cytochrome c to the cytosol and
      bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured
      using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8
      min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation
      followed by 240 min of postresuscitation hemodynamic observation. A sham group
      served as control. Plasma cytochrome c rose progressively to levels 10-fold
      higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal
      of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were
      inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02).
      Western immunoblotting of left ventricular tissue demonstrated increased levels
      of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was
      then serially measured in 12 resuscitated rats until the rat died or cytochrome c
      returned to baseline. In three survivors, cytochrome c rose slightly to <or=2
      microg/ml and returned to baseline within 96 h. In nine nonsurvivors, cytochrome
      c rose progressively to significantly higher maximal levels [4.6 (SD 2.0) vs. 1.6
      (SD 0.3) microg/ml, P = 0.029] and at faster rates [0.7 (SD 0.5) vs. 0.1 (SD 0.1)
      microg.ml(-1).h(-1), P = 0.046] than in survivors. Plasma cytochrome c may
      represent a novel in vivo marker of mitochondrial injury after resuscitation from
      cardiac arrest that relates inversely with survival outcome.

PMID- 17040976
TI  - Peroxynitrite diminishes myogenic tone in cerebral arteries: role of
      nitrotyrosine and F-actin.
AB  - This study investigated the effect of peroxynitrite (OONO(-))-induced
      nitrosylation of filamentous (F)-actin on myogenic tone in isolated and
      pressurized posterior cerebral arteries (PCAs). Immunohistochemical staining was
      used to determine 3-nitrotyrosine (NT) and F-actin content in vascular smooth
      muscle after exposure to 10(-7) M or 10(-4) M OONO(-) for 5 or 60 min in isolated
      third-order PCAs (n = 37) from male Wistar rats pressurized to 75 mmHg in an
      arteriograph chamber, quantified with confocal microscopy. Additionally, the role
      of K(+) channels in OONO(-)-induced dilation was investigated with 3 microM
      glibenclamide or 10 mM tetraethylammonium chloride before OONO(-) exposure. OONO(
      ) (10(-4) M) induced a 40% dilation of tone (P < 0.05) while diminishing F-actin
      content by half (P < 0.05) and causing a 60-fold increase in NT (P < 0.05) in the
      vascular smooth muscle of PCAs. Additionally, F-actin was inversely correlated
      with both diameter and NT content (P < 0.05) and was significantly colocalized in
      the vascular smooth muscle with NT (overlap coefficient = 0.8). The dilation to
      ONOO(-) was independent of K(+) channel activity and thiol oxidation as
      glibenclamide, tetraethylammonium chloride, and dithiothreitol had no effect on
      OONO(-)-induced dilation or F-actin or NT content in PCAs. Because NT was
      colocalized with F-actin, we hypothesize that OONO(-) induces nitrosylation of F
      actin in vascular smooth muscle leading to depolymerization and the subsequent
      loss of myogenic tone, which may promote vascular damage during oxidative stress
      such as in ischemia and reperfusion injury.

PMID- 17040977
TI  - Resources for integrative systems biology: from data through databases to
      networks and dynamic system models.
AB  - In systems biology, biologically relevant quantitative modelling of physiological
      processes requires the integration of experimental data from diverse sources.
      Recent developments in high-throughput methodologies enable the analysis of the
      transcriptome, proteome, interactome, metabolome and phenome on a previously
      unprecedented scale, thus contributing to the deluge of experimental data held in
      numerous public databases. In this review, we describe some of the databases and
      simulation tools that are relevant to systems biology and discuss a number of key
      issues affecting data integration and the challenges these pose to systems-level
      research.

PMID- 17040978
TI  - The treatment of coronary artery disease in patients with chronic kidney disease.
AB  - Premature cardiovascular disease is the largest cause of mortality, and a major
      cause of morbidity, in patients with chronic kidney disease (CKD). Patients with
      end-stage kidney disease (ESKD) are at extreme risk, but cardiovascular event
      rates are increased even in early CKD. There is little controlled trial evidence
      on which to base treatment, as most therapeutic trials have excluded CKD
      patients. Current treatment strategies are therefore based upon small prospective
      studies or retrospective analyses of controlled trials and registry data. It is
      thus unclear whether CKD patients benefit from modern secondary preventive
      treatments in the same manner as patients with normal renal function. There is a
      need for randomized trials to identify effective drugs to prevent and treat
      coronary artery disease in CKD. Revascularization by CABG in CKD has been widely
      reported in registry data to provide better results than medical treatment or
      angioplasty. Recent angioplasty data in patients with CKD, however, show
      improving results, and the risks of CABG in CKD remain high. It is not clear
      which revascularization technique has a better outcome in patients 'equally
      suitable' on angiographic criteria for either procedure. The high rate of late
      adverse cardiovascular events after both CABG and angioplasty accentuates the
      need for effective secondary preventive therapy disease in these high-risk
      patients.

PMID- 17040979
TI  - Multiple diffusion mechanisms due to nanostructuring in crowded environments.
AB  - One of the key questions regarding intracellular diffusion is how the environment
      affects molecular mobility. Mostly, intracellular diffusion has been described as
      hindered, and the physical reasons for this behavior are: immobile barriers,
      molecular crowding, and binding interactions with immobile or mobile molecules.
      Using results from multi-photon fluorescence correlation spectroscopy, we
      describe how immobile barriers and crowding agents affect translational mobility.
      To study the hindrance produced by immobile barriers, we used sol-gels (silica
      nanostructures) that consist of a continuous solid phase and aqueous phase in
      which fluorescently tagged molecules diffuse. In the case of molecular crowding,
      translational mobility was assessed in increasing concentrations of 500 kDa
      dextran solutions. Diffusion of fluorescent tracers in both sol-gels and dextran
      solutions shows clear evidence of anomalous subdiffusion. In addition, data from
      the autocorrelation function were analyzed using the maximum entropy method as
      adapted to fluorescence correlation spectroscopy data and compared with the
      standard model that incorporates anomalous diffusion. The maximum entropy method
      revealed evidence of different diffusion mechanisms that had not been revealed
      using the anomalous diffusion model. These mechanisms likely correspond to
      nanostructuring in crowded environments and to the relative dimensions of the
      crowding agent with respect to the tracer molecule. Analysis with the maximum
      entropy method also revealed information about the degree of heterogeneity in the
      environment as reported by the behavior of diffusive molecules.

PMID- 17040980
TI  - Conformation of a peptide encompassing the proton translocation channel of
      vacuolar H(+)-ATPase.
AB  - The structural properties of a crucial transmembrane helix for proton
      translocation in vacuolar ATPase are studied using double site-directed spin
      labeling combined with electron spin resonance (ESR) (or electron paramagnetic
      resonance) and circular dichroism spectroscopy in sodium dodecyl sulfate
      micelles. For this purpose, we use a synthetic peptide derived from transmembrane
      helix 7 of subunit a from the yeast Saccharomyces cerevisiae vacuolar proton
      translocating ATPase that contains two natural cysteine residues suitable for
      spin-labeling. The interspin distance is calculated using a second-moment
      analysis of the methanethiosulfonate spin-label ESR spectra at 150 K. Molecular
      dynamics simulation is used to study the effect of the side-chain dynamics and
      backbone dynamics on the interspin distance. Based on the combined results from
      ESR, circular dichroism, and molecular dynamics simulation we conclude that the
      peptide forms a dynamic alpha-helix. We discuss this finding in the light of
      current models for proton translocation. A novel role for a buried charged
      residue (H729) is proposed.

PMID- 17040981
TI  - Membrane order and molecular dynamics associated with IgE receptor cross-linking
      in mast cells.
AB  - Cholesterol-rich microdomains (or "lipid rafts") within the plasma membrane have
      been hypothesized to exist in a liquid-ordered phase and play functionally
      important roles in cell signaling; however, these microdomains defy detection
      using conventional imaging. To visualize domains and relate their nanostructure
      and dynamics to mast cell signaling, we use two-photon (760 nm and 960 nm)
      fluorescence lifetime imaging microscopy and fluorescence polarization anisotropy
      imaging, with comparative one-photon anisotropy imaging and single-point lifetime
      and anisotropy decay measurements. The inherent sensitivity of ultrafast excited
      state dynamics and rotational diffusion to the immediate surroundings of a
      fluorophore allows for real-time monitoring of membrane structure and
      organization. When the high affinity receptor for IgE (FcepsilonRI) is
      extensively cross-linked with anti-IgE, molecules associated with cholesterol
      rich microdomains (e.g., saturated lipids (the lipid analog diI-C(18) or
      glycosphingolipids)) and lipid-anchored proteins coredistribute with cross-linked
      IgE-FcepsilonRI. We find an enhancement in fluorescence lifetime and anisotropy
      of diI-C(18) and Alexa 488-labeled IgE-FcepsilonRI in the domains where these
      molecules colocalize. Our results suggest that fluorescence lifetime and,
      particularly, anisotropy permit us to correlate the recruitment of lipid
      molecules into more ordered domains that serve as platforms for IgE-mediated
      signaling.

PMID- 17040982
TI  - pK(a) values for side-chain carboxyl groups of a PGB1 variant explain salt and pH
      dependent stability.
AB  - Determination of pK(a) values of titrating residues in proteins provides a direct
      means of studying electrostatic coupling as well as pH-dependent stability. The
      B1 domain of protein G provides an excellent model system for such
      investigations. In this work, we analyze the observed pK(a) values of all
      carboxyl groups in a variant of PGB1 (T2Q, N8D, N37D) at low and high ionic
      strength as determined using (1)H-(13)C heteronuclear NMR in a structural
      context. The pK(a) values are used to calculate the pH-dependent stability in low
      and high salt and to investigate electrostatic coupling in the system. The
      observed pK(a) values can explain the pH dependence of protein stability but
      require pK(a) shifts relative to model values in the unfolded state, consistent
      with persistent residual structure in the denatured state. In particular, we find
      that most of the deviations from the expected random coil values can be explained
      by a significantly upshifted pK(a) value. We show also that (13)C backbone
      carbonyl data can be used to study electrostatic coupling in proteins and provide
      specific information on hydrogen bonding and electrostatic potential at
      nontitrating sites.

PMID- 17040984
TI  - Modeling a spin-labeled fusion peptide in a membrane: implications for the
      interpretation of EPR experiments.
AB  - Site-directed spin-labeling and electron paramagnetic resonance are powerful
      tools for studying structure and conformational dynamics of proteins, especially
      in membranes. The position of the spin label is used as an indicator of the
      position of the site to which it is attached. The interpretation of these
      experiments is based on the assumptions that the spin label does not affect the
      peptide configuration and that it has a fixed orientation and distance with
      respect to the protein backbone. Here, the validity of these assumptions is
      examined through implicit membrane molecular dynamics simulations of the
      influenza hemagglutinin fusion peptide that has been labeled with
      methanethiosulfonate spin label. We find that the methanethiosulfonate spin label
      can occasionally induce peptide orientations that differ from those adopted by
      the wild-type peptide. Furthermore, the spin-label resides, on average, several
      Angstroms deeper in the membrane than the corresponding backbone C(alpha)-atom
      even at sites pointing toward the solvent. The nitroxide spin label exhibits
      flexibility and adopts various configurations depending on the surrounding
      residues.

PMID- 17040983
TI  - Three-color alternating-laser excitation of single molecules: monitoring multiple
      interactions and distances.
AB  - We introduce three-color alternating-laser excitation (3c-ALEX), a fluorescence
      resonance energy transfer (FRET) method that measures up to three intramolecular
      distances and complex interaction stoichiometries of single molecules in
      solution. This tool extends substantially the capabilities of two-color ALEX,
      which employs two alternating lasers to study molecular interactions (through
      probe stoichiometry S) and intramolecular distances (through FRET efficiency E),
      and sorts fluorescent molecules in multi-dimensional probe-stoichiometry and FRET
      efficiency histograms. Probe-stoichiometry histograms allowed analytical sorting,
      identification, and selection of diffusing species; selected molecules were
      subsequently represented in FRET-efficiency histograms, generating up to three
      intramolecular distances. Using triply labeled DNAs, we established that 3c-ALEX
      enables 1), FRET-independent analysis of three-component interactions; 2),
      observation and sorting of singly, doubly, and triply labeled molecules
      simultaneously present in solution; 3), measurements of three intramolecular
      distances within single molecules from a single measurement; and 4), dissection
      of conformational heterogeneity with improved resolution compared to conventional
      single-molecule FRET. We also used 3c-ALEX to study large biomolecules such as
      RNA polymerase-DNA transcription complexes, and monitor the downstream
      translocation of RNA polymerase on DNA from two perspectives within the complex.
      This study paves the way for advanced single-molecule analysis of complex
      mixtures and biomolecular machinery.

PMID- 17040985
TI  - pH-dependent self-assembly of polyalanine peptides.
AB  - Polyalanine expansions in the nuclear RNA-binding protein PABP2 induce misfolding
      and aggregation of the protein into insoluble inclusions in muscle tissues and
      cell nuclei, leading to the disease oculopharyngeal muscular dystrophy (OPMD). We
      have explored the effect of solvent conditions and alanine repeat number on the
      propensity of fibril formation in this protein deposition disease. Three peptides
      mimicking the N-terminal polyalanine segment of PABP2, having the generic
      sequence Ac-Lys-Met-(Ala)(n)-Gly-Tyr with n = 7, 11, and 17 (referred to as 7
      ala, 11-ala, and 17-ala, respectively), were synthesized and their conformational
      properties studied as a function of pH. In strongly alkaline medium (pH >10), the
      two longer peptides (11-ala and 17-ala, but not 7-ala) showed remarkable
      enhancement of beta-sheet content and formed fibrils after incubation for 1-2
      weeks at room temperature. Fluorescence studies suggested that tyrosyl radicals
      produced at high pH cross-linked to form dityrosine, which provided added
      stabilization for fibril growth. The kinetic progress curves for fibril
      formation, obtained by ThT fluorescence assay, showed exponential increase with
      time after an initial quiescent period (lag time) and an eventual saturation
      phase, all of which are indicative of a nucleation-controlled polymerization
      mechanism for fibrillation. Hierarchical self-assembly of the peptides led to the
      formation of striking fractal-shaped growth patterns on substrates, raising the
      possibility of designing novel materials using these peptides.

PMID- 17040986
TI  - Conformational sampling with implicit solvent models: application to the PHF6
      peptide in tau protein.
AB  - Implicit solvent models approximate the effects of solvent through a potential of
      mean force and therefore make solvated simulations computationally efficient. Yet
      despite their computational efficiency, the inherent approximations made by
      implicit solvent models can sometimes lead to inaccurate results. To test the
      accuracy of a number of popular implicit solvent models, we determined whether
      implicit solvent simulations can reproduce the set of potential energy minima
      obtained from explicit solvent simulations. For these studies, we focus on a six
      residue amino-acid sequence, referred to as the paired helical filament 6 (PHF6),
      which may play an important role in the formation of intracellular aggregates in
      patients with Alzheimer's disease. Several implicit solvent models form the basis
      of this work--two based on the generalized Born formalism, and one based on a
      Gaussian solvent-exclusion model. All three implicit solvent models generate
      minima that are in good agreement with minima obtained from simulations with
      explicit solvent. Moreover, free-energy profiles generated with each implicit
      solvent model agree with free-energy profiles obtained with explicit solvent. For
      the Gaussian solvent-exclusion model, we demonstrate that a straightforward
      ranking of the relative stability of each minimum suggests that the most stable
      structure is extended, a result in excellent agreement with the free-energy
      profiles. Overall, our data demonstrate that for some peptides like PHF6,
      implicit solvent can accurately reproduce the set of local energy minimum arising
      from quenched dynamics simulations with explicit solvent. More importantly, all
      solvent models predict that PHF6 forms extended beta-structures in solution, a
      finding consistent with the notion that PHF6 initiates neurofibrillary tangle
      formation in patients with Alzheimer's disease.

PMID- 17040988
TI  - Cerulean, Venus, and VenusY67C FRET reference standards.
AB  - Forster's resonance energy transfer (FRET) can be used to study protein-protein
      interactions in living cells. Numerous methods to measure FRET have been devised
      and implemented; however, the accuracy of these methods is unknown, which makes
      interpretation of FRET efficiency values difficult if not impossible. This
      problem exists due to the lack of standards with known FRET efficiencies that can
      be used to validate FRET measurements. The advent of spectral variants of green
      fluorescent protein and easy access to cell transfection technology suggests a
      simple solution to this problem: the development of genetic constructs with known
      FRET efficiencies that can be replicated with high fidelity and freely
      distributed. In this study, fluorescent protein constructs with progressively
      larger separation distances between donors and acceptors were generated and FRET
      efficiencies were measured using fluorescence lifetime spectroscopy, sensitized
      acceptor emission, and spectral imaging. Since the results from each method were
      in good agreement, the FRET efficiency value of each construct could be
      determined with high accuracy and precision, thereby justifying their use as
      standards.

PMID- 17040987
TI  - Enhanced surfactant adsorption via polymer depletion forces: a simple model for
      reversing surfactant inhibition in acute respiratory distress syndrome.
AB  - Lung surfactant adsorption to an air-water interface is strongly inhibited by an
      energy barrier imposed by the competitive adsorption of albumin and other surface
      active serum proteins that are present in the lung during acute respiratory
      distress syndrome. This reduction in surfactant adsorption results in an
      increased surface tension in the lung and an increase in the work of breathing.
      The reduction in surfactant adsorption is quantitatively described using a
      variation of the classical Smolukowski analysis of colloid stability. Albumin
      adsorbed to the interface induces an energy barrier to surfactant diffusion of
      order 5 k(B)T, leading to a reduction in adsorption equivalent to reducing the
      surfactant concentration by a factor of 100. Adding hydrophilic, nonadsorbing
      polymers such as polyethylene glycol to the subphase provides a depletion
      attraction between the surfactant aggregates and the interface that eliminates
      the energy barrier. Surfactant adsorption increases exponentially with polymer
      concentration as predicted by the simple Asakura and Oosawa model of depletion
      attraction. Depletion forces can likely be used to overcome barriers to
      adsorption at a variety of liquid-vapor and solid-liquid interfaces.

PMID- 17040989
TI  - Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin.
AB  - Sickle cell hemoglobin (HbS) is a mutant, whose polymerization while in deoxy
      state in the venous circulation underlies the debilitating sickle cell anemia. It
      has been suggested that the nucleation of the HbS polymers occurs within clusters
      of dense liquid, existing in HbS solutions. We use dynamic light scattering with
      solutions of deoxy-HbS, and, for comparison, of oxy-HbS and oxy-normal adult
      hemoglobin, HbA. We show that solutions of all three Hb variants contain clusters
      of dense liquid, several hundred nanometers in size, which are metastable with
      respect to the Hb solutions. The clusters form within a few seconds after
      solution preparation and their sizes and numbers remain relatively steady for up
      to 3 h. The lower bound of the cluster lifetime is 15 ms. The clusters exist in
      broad temperature and Hb concentration ranges, and occupy 10(-5)-10(-2) of the
      solution volume. The results on the cluster properties can serve as test data for
      a potential future microscopic theory of cluster stability and kinetics. More
      importantly, if the clusters are a part of the nucleation mechanism of HbS
      polymers, the rate of HbS polymerization can be controlled by varying the cluster
      properties.

PMID- 17040990
TI  - Structural features of parathyroid hormone receptor coupled to Galpha(s)-protein.
AB  - The molecular basis of the activation of G-proteins by the G-protein coupled
      receptor for parathyroid hormone (PTH) is unknown. Employing a combination of NMR
      methods and computer-based structural refinement, structural features involved in
      the activation of Galpha(s) by the PTH receptor (PTH1R) have been determined.
      Focusing on the C-terminus of the third intracellular loop (IC3), previously
      shown to be important for Galpha(s) activation by PTH1R, the structure of this
      region, PTH1R(402-408), while bound to Galpha(s), was determined by transferred
      nuclear Overhauser effect spectroscopy. The relative topological orientation of
      the IC3 while associated with Galpha(s) was determined by saturation transfer
      difference spectroscopy. These experimental data were incorporated into molecular
      dynamics simulations of the PTH1R and Galpha(s) to provide atomic insight into
      the receptor-protein interactions important for PTH signaling and a structural
      framework to analyze previous mutagenesis studies of Galpha(s). These data
      provide the first step toward development of a molecular mechanism for the
      signaling profile of PTH1R, an important regulator of calcium levels in the
      bloodstream.

PMID- 17040991
TI  - The gas-phase absorption spectrum of a neutral GFP model chromophore.
AB  - We have studied the gas-phase absorption properties of the green fluorescent
      protein (GFP) chromophore in its neutral (protonated) charge state in a heavy-ion
      storage ring. To accomplish this we synthesized a new molecular chromophore with
      a charged NH(3) group attached to a neutral model chromophore of GFP. The gas
      phase absorption cross section of this chromophore molecule as a function of the
      wavelength is compared to the well-known absorption profile of GFP. The
      chromophore has a maximum absorption at 415 +/- 5 nm. When corrected for the
      presence of the charged group attached to the GFP model chromophore, the
      unperturbed neutral chromophore is predicted to have an absorption maximum at 399
      nm in vacuum. This is very close to the corresponding absorption peak of the
      protein at 397 nm. Together with previous data obtained with an anionic GFP model
      chromophore, the present data show that the absorption of GFP is primarily
      determined by intrinsic chromophore properties. In other words, there is strong
      experimental evidence that, in terms of absorption, the conditions in the
      hydrophobic interior of this protein are very close to those in vacuum.

PMID- 17040993
TI  - A prospective study of anaemia and long-term outcomes in kidney transplant
      recipients.
AB  - BACKGROUND: Anaemia is prevalent in kidney transplant recipients (KTR), and only
      few KTR with anaemia receive treatment with erythropoietin. Some have claimed
      that this undertreatment might contribute to suboptimal outcomes such as
      mortality and cardiovascular events in these patients. However, no evidence is
      currently available that anaemia is actually associated with such risks in KTR.
      METHODS: We merged two cohorts of KTR to study the associations between anaemia
      and two outcomes: all-cause mortality and kidney allograft loss. Detailed
      information on the demographic and clinical characteristics of these 825 patients
      was available at baseline. As recommended by the American Society of
      Transplantation, anaemia was considered present if the haemoglobin concentration
      was < or =13 g/dl in men or < or =12 g/dl in women. Patients were followed using
      the Austrian Dialysis and Transplant Registry. RESULTS: After 8.2 years of follow
      up, 251 patients died and 401 allografts were lost. In multivariate analyses,
      anaemia was not associated with all-cause mortality (HR: 1.08; 95% CI: 0.80
      1.45), but it was associated with 25% greater risk of allograft loss (HR = 1.25;
      95% CI: 1.02-1.59). This association was even more pronounced in death-censored
      analyses. Analyses using haemoglobin as a continuous variable or in categories
      also found no association with mortality. CONCLUSIONS: Anaemia may not be
      associated with mortality in KTR. In light of the recent findings of increased
      mortality in chronic kidney disease patients with higher haemoglobin treatment
      target, further evidence is needed to guide clinicians in the treatment of
      anaemia in these patients.

PMID- 17040992
TI  - A mathematical model of glioblastoma tumor spheroid invasion in a three
      dimensional in vitro experiment.
AB  - Glioblastoma, the most malignant form of brain cancer, is responsible for 23% of
      primary brain tumors and has extremely poor outcome. Confounding the clinical
      management of glioblastomas is the extreme local invasiveness of these cancer
      cells. The mechanisms that govern invasion are poorly understood. To gain insight
      into glioblastoma invasion, we conducted experiments on the patterns of growth
      and dispersion of U87 glioblastoma tumor spheroids in a three-dimensional
      collagen gel. We studied two different cell lines, one with a mutation to the
      EGFR (U87DeltaEGFR) that is associated with increased malignancy, and one with an
      endogenous (wild-type) receptor (U87WT). We developed a continuum mathematical
      model of the dispersion behaviors with the aim of identifying and characterizing
      discrete cellular mechanisms underlying invasive cell motility. The mathematical
      model quantitatively reproduces the experimental data, and indicates that the
      U87WT invasive cells have a stronger directional motility bias away from the
      spheroid center as well as a faster rate of cell shedding compared to the
      U87DeltaEGFR cells. The model suggests that differences in tumor cell dispersion
      may be due to differences in the chemical factors produced by cells, differences
      in how the two cell lines remodel the gel, or different cell-cell adhesion
      characteristics.

PMID- 17040994
TI  - Markers of bone turnover in haemodialysis patients.

PMID- 17040995
TI  - P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte
      free radical production.
AB  - BACKGROUND: Chronic renal insufficiency is associated with the retention of
      solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound
      uraemic retention solute, has been shown to exert toxic effects in vitro.
      Recently, however, it has been demonstrated that p-cresol in the human body is
      conjugated, with p-cresylsulphate as the main metabolite. METHODS: The present
      study evaluates the effect of p-cresylsulphate on the respiratory burst activity
      of leucocytes. RESULTS: P-cresylsulphate significantly increased the percentage
      of leucocytes displaying oxidative burst activity at baseline. Oxidative burst
      activity of stimulated leucocytes was however not affected. In contrast, p-cresol
      had no effect on the leucocytes at baseline, but inhibited leucocytes burst
      activity after stimulation. CONCLUSION: The present study demonstrates, for the
      first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a
      pro-inflammatory effect on unstimulated leucocytes. This effect could contribute
      to the propensity to vascular disease in the uraemic population.

PMID- 17040996
TI  - A nationwide blood spot screening study for Fabry disease in the Czech Republic
      haemodialysis patient population.
AB  - BACKGROUND: Fabry disease (FD) is a genetic disorder characterized by
      accumulation of trihexosylceramide in lysosomes of various tissues leading to
      multiorgan manifestations, including progressive renal disease. Previous
      screening studies have shown that a non-neglectable proportion of
      haemodialysis(HD) patients have unsuspected FD. An extensive FD screening study,
      the largest to date, has been conducted in HD patients in Czech Republic. We
      aimed to uncover previously undiagnosed FD patients, to enable them to benefit
      from cause-specific therapeutic intervention with enzyme replacement therapy
      (ERT). METHODS: Large-scale screening was executed using a convenient automated
      enzymatic (alpha-galactosidose A, alpha-Gal A) dried blood spot on filter paper
      fluorescence method. RESULTS: In total, 3370 (45.1% males, 54.9% females) out of
      4058 HD patients (83%) in Czech Republic participated in this blood spot
      screening (BSS) study. Abnormal low fluorescence readings were obtained in 117
      patients (3.5%). Subsequent determination of plasma alpha-Gal A activity
      identified four males and three females with deficient plasma enzyme activity.
      Determination of alpha-Gal A activity in peripheral blood leucocytes and
      confirmatory molecular analysis resulted in four newly diagnosed Fabry males and
      one female. Subsequent family screening identified 10 family members with
      genotypically proven FD. Based on these screening results, ERT could be offered
      to five male FD patients. CONCLUSIONS: BSS represents a promising screening tool
      that has proven to be convenient and effective in uncovering unrecognized FD
      patients among the chronic HD population in Czech Republic.

PMID- 17040997
TI  - Increased expression of the pro-apoptotic ATP-sensitive P2X7 receptor in
      experimental and human glomerulonephritis.
AB  - BACKGROUND: The involvement of IL-1beta and other pro-inflammatory cytokines in
      most forms of glomerulonephritis is now well established. The P2X(7) receptor, an
      ATP-sensitive P2X receptor, functions not only as a non-selective cation channel,
      but it is also involved in the rapid processing and release of IL-1beta,
      apoptosis and necrotic cell death. Therefore, we wanted to investigate if
      expression of this receptor is altered in the glomeruli of rodent models of
      glomerulonephritis. METHODS: P2X(7) receptor protein expression was investigated
      using immunohistochemistry, and apoptosis was assessed using the TUNEL assay and
      caspase-3 immunostaining. Real-time PCR with gene-specific primers was used to
      detect P2X(7), IL-1beta, p53, bax and bcl-2 mRNA expression. RESULTS: Although
      the levels of the P2X(7) receptor protein in mouse kidney are normally very low,
      or undetectable, we detected an increase in glomerular expression of this
      receptor and an increase in glomerular apoptotic cells in a mouse model of
      accelerated nephrotoxic nephritis. We also observed increased glomerular and
      tubular expression of the P2X(7) receptor protein in renal biopsy tissue of
      patients with autoimmune-related glomerulonephritis. Furthermore, P2X(7) receptor
      mRNA increased in the kidneys of a rat model of proliferative glomerulonephritis
      and this coincided with the onset of proteinuria. We also observed increased mRNA
      expression of Il-1beta and the pro-apoptotic markers p53 and bax, but not of anti
      apoptotic bcl-2. CONCLUSION: Although there is an association between expression
      of the pro-inflammatory and pro-apoptotic P2X(7) receptor and glomerulonephritis
      in these rodent models, and in at least one form of human glomerulonephritis, the
      underlying relationship and its functional significance remain to be explored.

PMID- 17040998
TI  - Kidney biopsy in myeloma.

PMID- 17040999
TI  - Which cardiovascular risk factors matter in chronic kidney disease?

PMID- 17041000
TI  - Mitomycin- and calcineurin-associated HUS, endothelial dysfunction and
      endothelial repair: a new paradigm for the puzzle?

PMID- 17041001
TI  - Effect of risedronate on high-dose corticosteroid-induced bone loss in patients
      with glomerular disease.
AB  - BACKGROUND: Corticosteroids are often used for the treatment of glomerular
      diseases. We examined whether bisphosphonate or vitamin D3 has beneficial effects
      on bone mineral density (BMD) in patients with glomerular diseases being treated
      with high-dose corticosteroids, including pulse therapy. METHODS: Thirty-eight
      patients (19 men and 19 women, aged 42 +/- 16 years) were randomized into three
      groups: bisphosphonate alone (risedronate 2.5 mg/day, group R, n = 12), vitamin
      D3 alone (alfacalcidol 0.5 mug/day, group A, n = 15) and the combination of both
      agents (group R+A, n = 11). BMD at the lumbar spine was measured before and 12
      months after treatment. The biochemical parameters of bone metabolism were
      assessed before and 3, 6 and 12 months after treatment. RESULTS: In group R+A,
      BMD was significantly increased (+2.0%), whereas BMD was significantly decreased
      in group A (-5.6%). The BMD in group R did not show a significant change. In
      patients treated with steroid-pulse, BMD was decreased in groups R and A. In
      group R+A, BMD was significantly increased (+2.1%). Serum osteocalcin and
      alkaline phosphatase levels, markers of bone formation, were significantly
      decreased in all groups. Urinary crosslinked N-telopeptide of type I collagen
      (NTx) levels, a marker of bone resorption, were decreased in groups R and R+A. In
      patients with decreased BMD, the urinary NTx levels at baseline were
      significantly higher than the patients with increased BMD. CONCLUSIONS:
      Bisphosphonate might be beneficial for the prevention of steroid-induced bone
      loss in patients with glomerular diseases compared with vitamin D3. The combined
      therapy may be more effective, especially in patients treated with high-dose
      corticosteroids, including pulse therapy. A high urinary NTx level before
      receiving corticosteroids might be a predictive marker of the loss of BMD.

PMID- 17041002
TI  - Interview with Dr. Maurizio C. Capogrossi regarding pivotal advance: high
      mobility group box 1 protein--a cytokine with a role in cardiac repair. Interview
      by Helene F. Rosenberg and Joost J Oppenheim.

PMID- 17041003
TI  - Aggravation of intestinal inflammation by depletion/deficiency of gammadelta T
      cells in different types of IBD animal models.
AB  - The role of gammadelta T cells in inflammatory bowel disease (IBD) is still
      controversial. Although gammadelta T cells induce IBD in immunodeficient animals,
      others suggest a protective role of gammadelta T cells. Therefore, this study was
      conducted in order to elucidate the effect of gammadelta T cell
      depletion/deficiency on different IBD animal models. Mice depleted of or
      deficient in gammadelta T cells were exposed to dextran sodium sulfate (DSS) in
      order to induce colitis. In addition, gammadelta T cells were depleted in mice
      with terminal ileitis (TNFDeltaARE) or colitis due to interleukin 2 deficiency
      (IL-2 ko). Finally, DSS-induced colitis was studied in mice deficient in
      interferon gamma (IFN-gamma ko) upon gammadelta T cell depletion. Depletion of
      gammadelta T cells aggravated DSS-induced colitis and terminal ileitis of
      TNFDeltaARE mice. Exacerbated DSS-induced colitis was also found in gammadelta T
      cell-deficient mice. IL-2 ko mice showed increased mortality upon early (starting
      at 4 wk of age) but not late depletion (starting at 8 wk of age). Early
      gammadelta T cell depletion or deficiency resulted in increased IFN-gamma
      production by both lamina propria lymphocytes and splenocytes in every model
      investigated herein. In IFN-gamma ko mice, gammadelta T cell depletion did not
      affect the development and course of DSS-induced colitis. The protective effect
      of gammadelta T cells in IBD was confirmed in various IBD animal models.
      Particularly, during the early phase of intestinal inflammation, gammadelta T
      cells appear to be important. The mechanism seems to involve the control of IFN
      gamma production and epithelial regeneration.

PMID- 17041004
TI  - The melanocortin system in leukocyte biology.
AB  - The melanocortin system is composed of the melanocortin peptides,
      adrenocorticotropic hormone and alpha-, beta-, and gamma-melanocyte-stimulating
      hormone, the melanocortin receptors (MCRs), and the endogenous antagonists agouti
      and agouti-related protein. Melanocortin peptides exert multiple effects upon
      the host, including anti-inflammatory and immunomodulatory effects. Leukocytes
      are a source of melanocortins and a major target for these peptides. Because of
      reduced translocation of the nuclear factor NF-kappaB to the nucleus, MCR
      activation by their ligands causes a collective reduction of the most important
      molecules involved in the inflammatory process. This review examines how
      melanocortin peptides and their receptors participate in leukocyte biology.

PMID- 17041005
TI  - Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by
      cannabinoids.
AB  - Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and
      CB2. In this report, we investigated whether CBs regulate gene expression of
      their cognate receptors in T cells and studied underlying mechanisms in CD4+
      Jurkat T cells. Transcription of the CB1 gene was strongly induced in response to
      Delta9-tetrahydrocannabinol (THC), whereas the CB2 gene was not regulated. The
      induction of CB1 gene expression is mediated by CB2 receptors only, as
      demonstrated by using the CB1 and CB2 agonists R(+)-methanandamide and JWH 015,
      respectively, and combinations of THC plus CB1- and CB2-specific antagonists.
      After activation of CB2 receptors, the transcription factor STAT5 is
      phosphorylated. STAT5 then transactivates IL-4. Induction of IL-4 mRNA as well as
      IL-4 protein release from the cells are necessary for the following induction of
      the CB1 gene. This was demonstrated by using decoy oligonucleotides against
      STAT5, which blocked IL-4 and CB1 mRNA induction, and by using the IL-4 receptor
      antagonist IL-4 [R121D,Y124D], which blocked the up-regulation of CB1 gene
      transcription. Transactivation of the CB1 gene in response to IL-4 is then
      mediated by the transcription factor STAT6, as shown by using decoy
      oligonucleotides against STAT6. An increase in CB1-mediated phosphorylation of
      MAPK in cells prestimulated with CB2-specific agonists suggests up-regulation of
      functional CB1 receptor proteins. In summary, up-regulation of CB1 in T
      lymphocytes in response to CBs themselves may facilitate or enhance the various
      immunomodulatory effects related to CBs.

PMID- 17041006
TI  - A p38alpha selective mitogen-activated protein kinase inhibitor prevents
      periodontal bone loss.
AB  - In the oral microbial environment, Gram-negative bacterial derived
      lipopolysaccharide (LPS) can initiate inflammatory bone loss as seen in
      periodontal diseases. p38 Mitogen-activated protein kinase (MAPK) signaling is
      critical to inflammatory cytokine and LPS-induced cytokine expression, which may
      contribute toward periodontal bone loss. The purpose of this proof-of-principle
      study was to evaluate the ability of an orally active p38alpha MAPK inhibitor (SD
      282) to reduce periopathogenic LPS-induced alveolar bone loss in an experimental
      rat model. Five groups of Sprague-Dawley rats received one of the following
      treatments: LPS injected to the palatal gingiva adjacent to the maxillary molars
      three times per week for 8 weeks, LPS plus two doses of SD-282 (15 or 45 mg/kg)
      twice daily by oral gavage, or control groups given drug vehicle (1% polyethylene
      glycol) or SD-282 (45 mg/kg) only. Baseline and 8-week alveolar bone loss was
      assessed by microcomputed tomography (microCT) and histological examination. LPS
      induced severe bone loss over this time period, whereas control groups were
      unchanged from baseline measurements. Both doses of SD-282 showed significant
      protection from LPS-induced bone loss. Bone area and volumetric analysis of
      maxillas by microCT indicated significant loss of bone volume with LPS treatment,
      which was blocked with the p38 inhibitor. Histological examination indicated
      significantly fewer tartate-resistant acid phosphatase-positive osteoclasts and a
      significant decrease in interleukin (IL)-6, IL-1beta, and tumor necrosis factor
      alpha expression in p38 inhibitor-treated groups compared with LPS groups by
      immunostaining. Results from this in vivo study suggest that orally active p38
      MAPK inhibitors can reduce LPS-induced inflammatory cytokine production and
      osteoclast formation and protect against LPS-stimulated alveolar bone loss.

PMID- 17041007
TI  - Nicotinic regulation of calcium/calmodulin-dependent protein kinase II activation
      in the spinal cord.
AB  - Recent studies have implicated the involvement of Ca2+-dependent mechanisms, in
      particular, calcium/calmodulin-protein kinase II in nicotine-induced
      antinociception using the tail-flick test. The spinal cord was suggested as a
      possible site of this involvement. The present study was undertaken to
      investigate the hypothesis that the beta2 nicotinic receptor subunit plays a
      central role in nicotine-induced spinal antinociception via calcium/calmodulin
      dependent calmodulin protein kinase II activation. The antinociceptive effects of
      i.t. nicotine in the tail-flick test did not significantly differ in wild-type
      and alpha7 knockout (KO) animals but were lost in beta2 knockout mice. When
      calcium/calmodulin-dependent calmodulin protein kinase II activity in the lumbar
      spinal cord after acute i.t. administration of nicotine was investigated in wild
      type and beta2 and alpha7 knockout mice, the increase in calcium/calmodulin
      dependent calmodulin protein kinase II activity was not significant reduced in
      alpha7 KO mice but was eliminated in the beta2 KO mice. In addition, L-type
      calcium channel blockers nimodipine and verapamil but not the N-methyl-D
      aspartate antagonist MK-801 (dizocilpine maleate) blocked the increase in the
      kinase activity induced by nicotine. Taken together, these results are consistent
      with the hypothesis that increases in intracellular calcium result in activation
      of calcium-mediated second messengers in the spinal cord that play an important
      role in nicotine-induced antinociception as measured in the tail-flick test.
      Furthermore, our findings indicate that nicotinic stimulation of beta2-containing
      acetylcholine nicotinic receptors in the spinal cord can activate
      calcium/calmodulin-dependent calmodulin protein kinase II and produce nicotinic
      analgesia, which may require L-type calcium voltage and gated channels but not
      the intervention of glutamatergic transmission.

PMID- 17041008
TI  - Relative activation of human pregnane X receptor versus constitutive androstane
      receptor defines distinct classes of CYP2B6 and CYP3A4 inducers.
AB  - Both the human pregnane X receptor (hPXR) and constitutive androstane receptor
      (hCAR) are capable of regulating CYP3A4 and CYP2B6 gene expression. However, the
      majority of currently identified CYP3A4 and CYP2B6 inducers are confirmed
      activators of hPXR but not hCAR. To compare these receptors with respect to their
      chemical selectivities, 16 drugs known to induce CYP3A4 and/or CYP2B expression
      were evaluated for relative activation of hPXR versus hCAR. Because of the high
      basal but low chemical-induced activation of hCAR in immortalized cells,
      alternative methods were used to evaluate hCAR activation potential. Thirteen of
      the 16 compounds were classified as moderate to strong hPXR activators. In
      contrast, carbamazepine (CMZ), efavirenz (EFV), and nevirapine (NVP) were
      classified as negligible or weak hPXR activators at concentrations associated
      with efficacious CYP2B6 reporter or endogenous gene induction in primary human
      hepatocytes, suggesting potential activation of hCAR. Subsequent experiments
      demonstrated that these three drugs efficiently induced nuclear accumulation of
      in vivo-transfected enhanced yellow fluorescent protein-hCAR and significantly
      increased expression of a CYP2B6 reporter gene when hCAR was expressed in CAR-/-
      mice. In addition, using a recently identified, chemically responsive splice
      variant of hCAR (hCAR3), the hCAR activation profiles of the 16 compounds were
      evaluated. By combining results from the hPXR- and hCAR3-based reporter gene
      assays, these inducers were classified as hPXR, hCAR, or hPXR/hCAR dual
      activators. Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and
      CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for
      in vitro prediction of chemical-mediated human CAR activation.

PMID- 17041009
TI  - Agonist and antagonist effects of 15R-prostaglandin (PG) D2 and 11-methylene-PGD2
      on human eosinophils and basophils.
AB  - Prostaglandin (PG) D2 acts through both the DP(1) receptor, which is coupled to
      adenylyl cyclase, and the DP2 receptor (chemoattractant receptor-homologous
      molecule expressed on Th2 cells), which is present on eosinophils, basophils, and
      Th2 cells and results in cell activation and migration. The most potent
      prostanoid DP2 agonist so far reported is 15R-methyl-PGD2, in which the hydroxyl
      group has the unnatural R configuration. In contrast, the corresponding analog
      possessing the natural 15S configuration is approximately 75 times less potent.
      This raised the question of whether the isoprostane 15R-PGD2 might have potent
      DP2 receptor-mediated biological activity. We therefore chemically synthesized
      15R-PGD2 and investigated its biological activity. This compound elicited DP2
      receptor-mediated CD11b expression in human basophils and eosinophils and induced
      actin polymerization and migration in eosinophils with a potency about the same
      as that of PGD2. In contrast, it had only a weak effect on DP1 receptor-mediated
      adenylyl cyclase activity in human platelets. We also investigated the effects of
      modification of the 9-hydroxyl and 11-oxo groups of PGD2. Both PGK2, in which the
      9-hydroxyl group is replaced by an oxo group, and 11-deoxy-11-methylene PGD2, in
      which the 11-oxo group is replaced by a CH2 group, have little or no DP1 or DP2
      agonist activity. However, the 11-methylene analog is a DP2 antagonist (IC50,
      approximately 2 microM). We conclude that 15R-PGD2, which may be generated by
      oxidative stress, is a potent and selective DP2 agonist and that modification of
      the 11-oxo group of PGD2 can result in DP2 antagonist activity.

PMID- 17041010
TI  - Sleep-disordered breathing in overweight and obese children and adolescents:
      prevalence, characteristics and the role of fat distribution.
AB  - AIMS: To determine the prevalence of sleep-disordered breathing (SDB) in a
      clinical sample of overweight and obese children and adolescents, and to examine
      the contribution of fat distribution. METHODS: Consecutive subjects without
      chronic lung disease, neuromuscular disease, laryngomalacia, or any genetic or
      craniofacial syndrome were recruited. All underwent measurements of neck and
      waist circumference, waist-to-hip ratio, % fat mass and polysomnography.
      Obstructive apnoea index > or =1 or obstructive apnoea-hypopnoea index (OAHI) >
      or =2, further classified as mild (2< or =OAHI<5) or moderate-to-severe (OAHI> or
      =5), were used as diagnostic criteria for obstructive sleep apnoea (OSA). Central
      sleep apnoea was diagnosed when central apnoeas/hypopnoeas > or =10 s were
      present accompanied by >1 age-specific bradytachycardia and/or >1 desaturation
      <89%. Subjects with desaturation < or =85% after central events of any duration
      were also diagnosed with central sleep apnoea. Primary snoring was diagnosed
      when: snoring was detected by microphone and normal obstructive indices and
      saturation. RESULTS: 27 overweight and 64 obese subjects were included (40 boys;
      mean (standard deviation (SD)) age 11.2 (2.6) years). Among the obese children,
      53% were normal, 11% had primary snoring, 11% had mild OSA, 8% had moderate-to
      severe OSA and 17% had central sleep apnoea. Half of the patients with central
      sleep apnoea had desaturation <85%. Only enlarged tonsils were predictive of
      moderate-to-severe OSA. On the other hand, higher levels of abdominal obesity and
      fat mass were associated with central sleep apnoea. CONCLUSION: SDB is very
      common in this clinical sample of overweight children. OSA is not associated with
      abdominal obesity. On the contrary, higher levels of abdominal obesity and fat
      mass are associated with central sleep apnoea.

PMID- 17041011
TI  - Tachykinin-1 receptor stimulates proinflammatory gene expression in lung
      epithelial cells through activation of NF-kappaB via a G(q)-dependent pathway.
AB  - The respiratory tract is innervated by irritant-responsive sensory nerves, which,
      on stimulation, release tachykinin neuropeptides in the lung. Tachykinins
      modulate inflammatory responses to injury by binding to tachykinin (neurokinin)
      receptors present on various pulmonary cell types. In the present study, the
      activation of the proinflammatory transcription factor NF-kappaB in lung
      epithelial cells was investigated as a mechanism by which tachykinins stimulate
      inflammatory processes. In A549 human lung epithelial cells transfected with the
      tachykinin-1 receptor (Tacr1), treatment with the Tacr1 ligand substance P (SP)
      resulted in NF-kappaB activation, as judged by transcription of an NF-kappaB
      luciferase reporter gene and production of interleukin-8, a chemokine whose
      expression is upregulated by NF-kappaB. SP caused a dose-dependent activation of
      NF-kappaB that was inhibited by the selective Tacr1 antagonist RP67580. Tacr1 is
      a G protein-coupled receptor capable of activating both the G(q) and G(s)
      families of G proteins. Expression of inhibitory peptides and constitutively
      active G protein mutants revealed that G(q) signaling was both necessary for
      Tacr1-induced NF-kappaB activation and sufficient for NF-kappaB activation in the
      absence of any other treatment. Treatment with pharmacological inhibitors to
      investigate events downstream of G(q) revealed that Tacr1-induced NF-kappaB
      activation proceeded through an intracellular signaling pathway that was
      dependent on phospholipase C, calcium, Ras, Raf-1, MEK, Erk, and proteasome
      function. These results identify intracellular signaling mechanisms that underlie
      the proinflammatory effects of tachykinins, which previously have been implicated
      in lung injury and disease.

PMID- 17041012
TI  - Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via
      RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications
      for chronic inflammation and aging.
AB  - The silent information regulator 2 (Sir2) family of proteins (sirtuins or SIRTs),
      which belong to class III histone/protein deacetylases, have been implicated in
      calorie restriction, aging, and inflammation. We hypothesized that cigarette
      smoke-mediated proinflammatory cytokine release is regulated by SIRT1 by its
      interaction with NF-kappaB in a monocyte-macrophage cell line (MonoMac6) and in
      inflammatory cells of rat lungs. Cigarette smoke extract (CSE) exposure to
      MonoMac6 cells caused dose- and time-dependent decreases in SIRT1 activity and
      levels, which was concomitant to increased NF-kappaB-dependent proinflammatory
      mediator release. Similar decrements in SIRT1 were also observed in inflammatory
      cells in the lungs of rats exposed to cigarette smoke as well as with increased
      levels of several NF-kappaB-dependent proinflammatory mediators in
      bronchoalveolar lavage fluid and in lungs. Sirtinol, an inhibitor of SIRT1,
      augmented, whereas resveratrol, an activator of SIRT1, inhibited CSE-mediated
      proinflammatory cytokine release. CSE-mediated inhibition of SIRT1 was associated
      with increased NF-kappaB levels. Furthermore, we showed that SIRT1 interacts with
      the RelA/p65 subunit of NF-kappaB, which was disrupted by cigarette smoke,
      leading to increased acetylation RelA/p65 in MonoMac6 cells. Thus our data show
      that SIRT1 regulates cigarette smoke-mediated proinflammatory mediator release
      via NF-kappaB, implicating a role of SIRT1 in sustained inflammation and aging of
      the lungs.

PMID- 17041013
TI  - Exploring host-pathogen interactions at the epithelial surface: application of
      transcriptomics in lung biology.
AB  - The epithelial surface of the airways is the largest barrier-forming interface
      between the human body and the outside world. It is now well recognized that, at
      this strategic position, airway epithelial cells play an eminent role in host
      defense by recognizing and responding to microbial exposure. Conversely, inhaled
      microorganisms also respond to contact with epithelial cells. Our understanding
      of this cross talk is limited, requiring sophisticated experimental approaches to
      analyze these complex interactions. High-throughput technologies, such as DNA
      microarray analysis and serial analysis of gene expression (SAGE), have been
      developed to screen for gene expression levels at large scale within single
      experiments. Since their introduction, these hypothesis-generating technologies
      have been widely used in diverse areas such as oncology and brain research.
      Successful application of these genomics-based technologies has also revealed
      novel insights in host-pathogen interactions in both the host and pathogen. This
      review aims to provide an overview of the SAGE and microarray technology
      illustrated by their application in the analysis of host-pathogen interactions.
      In particular, the interactions between epithelial cells in the human lungs and
      clinically relevant microorganisms are the central focus of this review.

PMID- 17041014
TI  - The reverse mode of the Na(+)/Ca(2+) exchanger provides a source of Ca(2+) for
      store refilling following agonist-induced Ca(2+) mobilization.
AB  - Agonist-induced contraction of airway smooth muscle (ASM) can be triggered by an
      elevation in the intracellular Ca(2+) concentration, primarily through the
      release of Ca(2+) from the sarcoplasmic reticulum (SR). The refilling of the SR
      is integral for subsequent contractions. It has been suggested that Ca(2+) entry
      via store-operated cation (SOC) and receptor-operated cation channels may
      facilitate refilling of the SR. Indeed, depletion of the SR activates substantial
      inward SOC currents in ASM that are composed of both Ca(2+) and Na(+).
      Accumulation of Na(+) within the cell may regulate Ca(2+) handling in ASM by
      forcing the Na(+)/Ca(2+) exchanger (NCX) into the reverse mode, leading to the
      influx of Ca(2+) from the extracellular domain. Since depletion of the SR
      activates substantial inward Na(+) current, it is conceivable that the reverse
      mode of the NCX may contribute to the intracellular Ca(2+) pool from which the SR
      is refilled. Indeed, successive contractions of bovine ASM, evoked by various
      agonists (ACh, histamine, 5-HT, caffeine) were significantly reduced upon removal
      of extracellular Na(+); whereas contractions evoked by KCl were unchanged by
      Na(+) depletion. Ouabain, a selective inhibitor of the Na(+)/K(+) pump, had no
      effect on the reductions observed under normal and zero-Na(+) conditions. KB
      R7943, a selective inhibitor of the reverse mode of the NCX, significantly
      reduced successive contractions induced by all agonists without altering KCl
      responses. Furthermore, KB-R7943 abolished successive caffeine-induced Ca(2+)
      transients in single ASM cells. Together, these data suggest a role for the
      reverse mode of the NCX in refilling the SR in ASM following Ca(2+) mobilization.

PMID- 17041015
TI  - Hydraulic conductance of lung endothelial phenotypes and Starling safety factors
      against edema.
AB  - Recent permeability studies comparing endothelial cell phenotypes derived from
      alveolar and extra-alveolar vessels have significant implications for
      interpreting the mechanisms of fluid homeostasis in the intact lung. These
      studies indicate that confluent monolayers of rat pulmonary microvascular
      endothelial cells had a hydraulic conductance (L(p)) that was only 5% and a
      transendothelial flux rate for 72-kDa dextran only 9% of values determined for
      rat pulmonary artery endothelial cell monolayers. On the basis of previous
      studies partitioning the filtration coefficients between alveolar and extra
      alveolar vascular segments in rat lungs and previous studies of lymph albumin
      fluxes and permeability, the contribution of the alveolar capillary segment to
      total albumin flux in lymph was estimated to be less than 10%. In addition, the
      Starling safety factors against the edema calculated for the alveolar capillaries
      are quite different from those estimated for whole lung. Estimates of the edema
      safety factor due to increased filtration across the alveolar capillary wall
      based on the low L(p) indicate it is quantitatively the greatest safety factor,
      although it would be a minor safety factor for extra-alveolar vessels. Also, a
      markedly higher effective protein osmotic absorptive force for plasma proteins
      must occur in the capillaries relative to extra-alveolar vessels. The lower L(p)
      for alveolar capillaries also has implications for the sequence of hydrostatic
      edema formation, and it also may have a role in preventing exercise-induced
      alveolar flooding.

PMID- 17041016
TI  - Self-perceived weight status and exercise adequacy.
AB  - The growing prevalence of obesity and inadequate physical activity levels in the
      population highlight an opportunity to examine public opinion about exercise, as
      well as the perceived adequacy of exercise among adults. This article summarizes
      findings from a 2004 survey of exercise habits and beliefs among Michigan adults
      using bivariate and logit analysis. It examines perceptions of weight status and
      adequacy of exercise, illuminates public opinion regarding the importance and
      value of exercise as one aspect of active living and highlights some of the
      perceived barriers and facilitators to exercise. The results indicate that people
      believe that they exercise enough, but that demographic, socio-economic and
      attitudinal factors may be potential barriers to physical activity. It is
      important to establish and/or bolster individual and community support structures
      while also minimizing potential barriers to exercise at the individual,
      organizational and community levels.

PMID- 17041017
TI  - Use of research by the Australian health promotion workforce.
AB  - This paper examines the attitudes and practices of Australian health promotion
      practitioners toward evidence-based practice (EBP). The study used a survey
      methodology and questionnaires were sent to 1114 members of the Australian Health
      Promotion Association. A response rate of 27% (n = 277) was achieved. The data
      showed that the vast majority of participant's attitudes toward EBP was very
      welcoming. However, in practice the impact of EBP was limited. Participants
      identified a range of significant barriers to implementing EBP including
      organizational culture, policy directives and lack of resources. A range of
      concerns was also identified regarding the applicability of the medically based
      EBP model within health promotion, which is based upon a social model of health.
      The findings highlight the importance of acknowledging the complexity of health
      promotion interventions and working toward developing an appropriate evidence
      base.

PMID- 17041018
TI  - Comparing stage of change and behavioral intention to understand fruit intake.
AB  - We explored if the pre-action Transtheoretical stages of change are indeed
      discrete stages for fruit intakes. In a longitudinal design, a cohort of 735
      adults completed electronic questionnaires assessing fruit intake, stages of
      change and intention to increase fruit intake at baseline and 35 and 67 days
      follow-up. A dichotomization of a continuous intention measure ('pseudostages')
      was compared with precontemplation and contemplation stages. The results showed
      (i) that pseudostages and stages of change were strongly associated; (ii) that
      for most respondents, stability and transitions in stages of change resembled
      transitions in pseudostage, while test-retest reliabilities for both measures
      were similar and (iii) that pseudostages and the continuous intention measure
      were stronger predictors of fruit intake than stage of change. We conclude that
      pre-action stages of change for fruit are not different from a mere
      categorization of a continuous intention measure.

PMID- 17041019
TI  - Nutrition knowledge and body mass index.
AB  - The purpose of this study was to investigate the relationship between nutrition
      knowledge and body mass index (BMI). The General Nutrition Questionnaire was
      distributed to 500 individuals on the database of a large general practice.
      Results demonstrated that there was no significant correlation between levels of
      nutrition knowledge and BMI; however, a high level of nutrition knowledge was
      found among the sample. This suggests that a knowledge deficit may not be the
      most significant factor preventing overweight individuals from adopting a
      healthier diet and questions the utility of purely educational approaches to
      dietary behaviour change. Evidence-based health behaviour change techniques are
      discussed.

PMID- 17041020
TI  - Young people and physical activity: a systematic review matching their views to
      effective interventions.
AB  - A systematic review was conducted to examine the barriers to, and facilitators
      of, physical activity among young people (11-16 years). The review focused on the
      wider determinants of health, examining community- and society-level
      interventions. Four trials and 16 studies of young people's views were included.
      Evidence for the effectiveness of the interventions was limited, with some
      suggestions of improvements in knowledge and possible differences according to
      gender. Young women in particular identified barriers to physical activity
      associated with certain ways of providing physical education in schools. Young
      people in general identified a need for increased choice and facilities within
      the community and emphasized physical activity's social side. Some of the
      barriers and facilitators identified by young people had been addressed by
      'soundly evaluated' effective interventions but significant gaps were identified
      where no evaluated interventions appear to have been published (e.g. initiatives
      explicitly addressing gender issues or the combination of sport and other leisure
      activities), or where there were no soundly evaluated interventions. Rigorous
      evaluation is required particularly to assess initiatives that address the
      limited practical and material resources that young people identify as barriers
      to physical activity.

PMID- 17041021
TI  - Infant-feeding attitudes of expectant mothers in Northern Ireland.
AB  - Northern Ireland (NI) has one of the lowest rates of breast-feeding initiation
      and duration in both the UK and the industrialized world. This study therefore
      aimed to explore the relationship between infant-feeding attitudes and feeding
      intention and outcome in expectant mothers within NI. Expectant mothers (n = 200)
      were recruited from hospital antenatal booking clinics. Each completed a
      demographic questionnaire and the self-administered Iowa Infant Feeding Attitude
      Scale (IIFAS). Participants (n = 192) were followed up after birth through the
      Northern Ireland Maternity System. The IIFAS distinguished between those mothers
      who intended to breast-feed (higher IIFAS scores) and those who intended to
      artificially feed (lower IIFAS scores) as well as between those who breast-fed
      and those who artificially fed on discharge from hospital. The IIFAS was also
      able to distinguish between mothers in regard to feeding intention and outcome on
      the basis of education, socio-economic class, income and marital status. This
      suggests that the IIFAS could prove useful in the targeting and evaluation of
      intervention to promote breast-feeding.

PMID- 17041022
TI  - Cultural accommodation of the Strengthening Families Programme 10-14: UK Phase I
      study.
AB  - Social and cultural differences between the United States and the United Kingdom
      mean that positive results from US prevention programmes may not translate to the
      United Kingdom. The Strengthening Families Programme 10-14 (SFP10-14) has been
      evaluated in a large Phase III randomized controlled trial in rural Iowa in the
      United States and shown to be effective for delaying alcohol and drug initiation.
      This paper reports the first stage of the adaptation and evaluation of the SFP10
      14 for the United Kingdom through a process of cultural accommodation of the
      SFP10-14 materials and format. Themes that emerged in nominal group and focus
      group research with young people and their parents indicated that changes to the
      US SFP10-14 materials needed to consider language, narrators, realism,
      acceptability of exercises/games, perceived religiosity and ethnic
      representativeness. However, not all changes reflected straightforward cultural
      differences, as adaptations were also required to improve the quality and to
      update the material, indicating that cultural accommodation does not necessarily
      imply cultural diversity.

PMID- 17041023
TI  - Dynamic response of prevacuolar compartments to brefeldin a in plant cells.
AB  - Little is known about the dynamics and molecular components of plant prevacuolar
      compartments (PVCs) in the secretory pathway. Using transgenic tobacco (Nicotiana
      tabacum) Bright-Yellow-2 (BY-2) cells expressing membrane-anchored yellow
      fluorescent protein (YFP) reporters marking Golgi or PVCs, we have recently
      demonstrated that PVCs are mobile multivesicular bodies defined by vacuolar
      sorting receptor proteins. Here, we demonstrate that Golgi and PVCs have
      different sensitivity in response to brefeldin A (BFA) treatment in living
      tobacco BY-2 cells. BFA at low concentrations (5-10 microg mL(-1)) induced YFP
      marked Golgi stacks to form both endoplasmic reticulum-Golgi hybrid structures
      and BFA-induced aggregates, but had little effect on YFP-marked PVCs in
      transgenic BY-2 cells at both confocal and immunogold electron microscopy levels.
      However, BFA at high concentrations (50-100 microg mL(-1)) caused both YFP-marked
      Golgi stacks and PVCs to form aggregates in a dose- and time-dependent manner.
      Normal Golgi or PVC signals can be recovered upon removal of BFA from the culture
      media. Confocal immunofluorescence and immunogold electron microscopy studies
      with specific organelle markers further demonstrate that the PVC aggregates are
      distinct, but physically associated, with Golgi aggregates in BFA-treated cells
      and that PVCs might lose their internal vesicle structures at high BFA
      concentration. In addition, vacuolar sorting receptor-marked PVCs in root-tip
      cells of tobacco, pea (Pisum sativum), mung bean (Vigna radiata), and Arabidopsis
      (Arabidopsis thaliana) upon BFA treatment are also induced to form similar
      aggregates. Thus, we have demonstrated that the effects of BFA are not limited to
      endoplasmic reticulum and Golgi, but extend to PVC in the endomembrane system,
      which might provide a quick tool for distinguishing Golgi from PVC for its
      identification and characterization, as well as a possible new tool in studying
      PVC-mediated protein traffic in plant cells.

PMID- 17041024
TI  - Common plantain. A collection of expressed sequence tags from vascular tissue and
      a simple and efficient transformation method.
AB  - The vascular tissue of higher plants consists of specialized cells that differ
      from all other cells with respect to their shape and size, their organellar
      composition, their extracellular matrix, the type of their plasmodesmata, and
      their physiological functions. Intact and pure vascular tissue can be isolated
      easily and rapidly from leaf blades of common plantain (Plantago major), a plant
      that has been used repeatedly for molecular studies of phloem transport. Here, we
      present a transcriptome analysis based on 5,900 expressed sequence tags (ESTs)
      and 3,247 independent mRNAs from the Plantago vasculature. The vascular
      specificity of these ESTs was confirmed by the identification of well-known
      phloem or xylem marker genes. Moreover, reverse transcription-polymerase chain
      reaction, macroarray, and northern analyses revealed genes and metabolic pathways
      that had previously not been described to be vascular specific. Moreover, common
      plantain transformation was established and used to confirm the vascular
      specificity of a Plantago promoter-beta-glucuronidase construct in transgenic
      Plantago plants. Eventually, the applicability and usefulness of the obtained
      data were also demonstrated for other plant species. Reporter gene constructs
      generated with promoters from Arabidopsis (Arabidopsis thaliana) homologs of
      newly identified Plantago vascular ESTs revealed vascular specificity of these
      genes in Arabidopsis as well. The presented vascular ESTs and the newly developed
      transformation system represent an important tool for future studies of
      functional genomics in the common plantain vasculature.

PMID- 17041025
TI  - SIZ1 small ubiquitin-like modifier E3 ligase facilitates basal thermotolerance in
      Arabidopsis independent of salicylic acid.
AB  - Small ubiquitin-like modifier (SUMO) conjugation/deconjugation to heat shock
      transcription factors regulates DNA binding of the peptides and activation of
      heat shock protein gene expression that modulates thermal adaptation in
      metazoans. SIZ1 is a SUMO E3 ligase that facilitates SUMO conjugation to
      substrate target proteins (sumoylation) in Arabidopsis (Arabidopsis thaliana).
      siz1 T-DNA insertional mutations (siz1-2 and siz1-3; Miura et al., 2005) cause
      basal, but not acquired, thermosensitivity that occurs in conjunction with
      hyperaccumulation of salicylic acid (SA). NahG encodes a salicylate hydroxylase,
      and expression in siz1-2 seedlings reduces endogenous SA accumulation to that of
      wild-type levels and further increases thermosensitivity. High temperature
      induces SUMO1/2 conjugation to peptides in wild type but to a substantially
      lesser degree in siz1 mutants. However, heat shock-induced expression of genes,
      including heat shock proteins, ascorbate peroxidase 1 and 2, is similar in siz1
      and wild-type seedlings. Together, these results indicate that SIZ1 and, by
      inference, sumoylation facilitate basal thermotolerance through processes that
      are SA independent.

PMID- 17041026
TI  - A eukaryotic factor required for accumulation of the chloroplast NAD(P)H
      dehydrogenase complex in Arabidopsis.
AB  - The NAD(P)H dehydrogenase (NDH) complex in chloroplasts mediates photosystem I
      cyclic and chlororespiratory electron transport. Eleven chloroplast genes and
      three nuclear genes have been identified as encoding Ndh subunits, but the entire
      subunit composition is still unknown. An Arabidopsis (Arabidopsis thaliana)
      chlororespiratory reduction (crr3) mutant was isolated based on its lack of
      transient increase in chlorophyll fluorescence after actinic light illumination;
      this was due to a specific defect in accumulation of the NDH complex. The CRR3
      gene (At2g01590) encodes a novel protein containing a putative plastid-targeting
      signal and a transmembrane domain. Consistent with the gene structure, CRR3
      localized to the membrane fraction of chloroplasts. In addition to the essential
      function of CRR3 in stabilizing the NDH complex, the NDH complex is also required
      for the accumulation of CRR3. These results suggest that CRR3 interacts with the
      NDH complex in the thylakoid membrane. In contrast to other subunits in the
      chloroplast NDH complex, CRR3 is not conserved in cyanobacteria from which the
      chloroplast NDH complex is believed to have originated. We propose that CRR3 is a
      subunit of the NDH complex, which is specific to the chloroplast.

PMID- 17041027
TI  - Geminivirus infection up-regulates the expression of two Arabidopsis protein
      kinases related to yeast SNF1- and mammalian AMPK-activating kinases.
AB  - Geminivirus Rep-interacting kinase 1 (GRIK1) and GRIK2 constitute a small protein
      kinase family in Arabidopsis (Arabidopsis thaliana). An earlier study showed that
      a truncated version of GRIK1 binds to the geminivirus replication protein AL1. We
      show here both full-length GRIK1 and GRIK2 interact with AL1 in yeast two-hybrid
      studies. Using specific antibodies, we showed that both Arabidopsis kinases are
      elevated in infected leaves. Immunoblot analysis of healthy plants revealed that
      GRIK1 and GRIK2 are highest in young leaf and floral tissues and low or
      undetectable in mature tissues. Immunohistochemical staining showed that the
      kinases accumulate in the shoot apical meristem, leaf primordium, and emerging
      petiole. Unlike the protein patterns, GRIK1 and GRIK2 transcript levels only show
      a small increase during infection and do not change significantly during
      development. Treating healthy seedlings and infected leaves with the proteasome
      inhibitor MG132 resulted in higher GRIK1 and GRIK2 protein levels, whereas
      treatment with the translation inhibitor cycloheximide reduced both kinases,
      demonstrating that their accumulation is modulated by posttranscriptional
      processes. Phylogenetic comparisons indicated that GRIK1, GRIK2, and related
      kinases from Medicago truncatula and rice (Oryza sativa) are most similar to the
      yeast kinases PAK1, TOS3, and ELM1 and the mammalian kinase CaMKK, which activate
      the yeast kinase SNF1 and its mammalian homolog AMPK, respectively.
      Complementation studies using a PAK1/TOS3/ELM1 triple mutant showed that GRIK1
      and GRIK2 can functionally replace the yeast kinases, suggesting that the
      Arabidopsis kinases mediate one or more processes during early plant development
      and geminivirus infection by activating SNF1-related kinases.

PMID- 17041028
TI  - Developmentally controlled farnesylation modulates AtNAP1;1 function in cell
      proliferation and cell expansion during Arabidopsis leaf development.
AB  - In multicellular organisms, organogenesis requires tight control and coordination
      of cell proliferation, cell expansion, and cell differentiation. We have
      identified Arabidopsis (Arabidopsis thaliana) nucleosome assembly protein 1
      (AtNAP1;1) as a component of a regulatory mechanism that connects cell
      proliferation to cell growth and expansion during Arabidopsis leaf development.
      Molecular, biochemical, and kinetic studies of AtNAP1;1 gain- or loss-of-function
      mutants indicate that AtNAP1;1 promotes cell proliferation or cell expansion in a
      developmental context and as a function of the farnesylation status of the
      protein. AtNAP1;1 was farnesylated and localized to the nucleus during the cell
      proliferation phase of leaf development when it promotes cell division. Later in
      leaf development, nonfarnesylated AtNAP1;1 accumulates in the cytoplasm when it
      promotes cell expansion. Ectopic expression of nonfarnesylated AtNAP1;1, which
      localized to the cytoplasm, disrupts this developmental program by promoting
      unscheduled cell expansion during the proliferation phase.

PMID- 17041030
TI  - NAD(P)H oscillates in pollen tubes and is correlated with tip growth.
AB  - The location and changes in NAD(P)H have been monitored during oscillatory growth
      in pollen tubes of lily (Lilium formosanum) using the endogenous fluorescence of
      the reduced coenzyme (excitation, 360 nm; emission, >400 nm). The strongest
      signal resides 20 to 40 microm behind the apex where mitochondria (stained with
      Mitotracker Green) accumulate. Measurements at 3-s intervals reveal that NAD(P)H
      dependent fluorescence oscillates during oscillatory growth. Cross-correlation
      analysis indicates that the peaks follow growth maxima by 7 to 11 s or 77 degrees
      to 116 degrees, whereas the troughs anticipate growth maxima by 5 to 10 s or 54
      degrees to 107 degrees. We have focused on the troughs because they anticipate
      growth and are as strongly correlated with growth as the peaks. Analysis of the
      signal in 10-microm increments along the length of the tube indicates that the
      troughs are most advanced in the extreme apex. However, this signal moves
      basipetally as a wave, being in phase with growth rate oscillations at 50 to 60
      microm from the apex. We suggest that the changes in fluorescence are due to an
      oscillation between the reduced (peaks) and oxidized (troughs) states of the
      coenzyme and that an increase in the oxidized state [NAD(P)(+)] may be coupled to
      the synthesis of ATP. We also show that diphenyleneiodonium, an inhibitor of
      NAD(P)H dehydrogenases, causes an increase in fluorescence and a decrease in tube
      growth. Finally, staining with 5-(and-6)-chloromethyl-2',7'
      dichlorohydrofluorescein acetate indicates that reactive oxygen species are most
      abundant in the region where mitochondria accumulate and where NAD(P)H
      fluorescence is maximal.

PMID- 17041029
TI  - Heterologous expression and molecular and cellular characterization of CaPUB1
      encoding a hot pepper U-Box E3 ubiquitin ligase homolog.
AB  - The U-box motif is a conserved domain found in the diverse isoforms of E3
      ubiquitin ligase in eukaryotes. From water-stressed hot pepper (Capsicum annuum
      L. cv Pukang) plants, we isolated C. annuum putative U-box protein 1 (CaPUB1),
      which encodes a protein containing a single U-box motif in its N-terminal region.
      In vitro ubiquitination and site-directed mutagenesis assays revealed that CaPUB1
      possessed E3 ubiquitin ligase activity and that the U-box motif was indeed
      essential for its enzyme activity. RNA gel-blot analysis showed that CaPUB1 mRNA
      was induced rapidly by a broad spectrum of abiotic stresses, including drought,
      high salinity, cold temperature, and mechanical wounding, but not in response to
      ethylene, abscisic acid, or a bacterial pathogen, suggesting its role in the
      early events in the abiotic-related defense response. Because transgenic work was
      extremely difficult in hot pepper, in this study we overexpressed CaPUB1 in
      Arabidopsis (Arabidopsis thaliana) to provide cellular information on the
      function of this gene in the development and plant responses to abiotic stresses.
      Transgenic Arabidopsis plants that constitutively expressed the CaPUB1 gene under
      the control of the cauliflower mosaic virus 35S promoter had markedly longer
      hypocotyls and roots and grew more rapidly than the wild type, leading to an
      early bolting phenotype. Microscopic analysis showed that 35S::CaPUB1 roots had
      increased numbers of small-sized cells, resulting in disordered, highly populated
      cell layers in the cortex, endodermis, and stele. In addition, CaPUB1
      overexpressing plants displayed increased sensitivity to water stress and mild
      salinity. These results indicate that CaPUB1 is functional in Arabidopsis cells,
      thereby effectively altering cell and tissue growth and also the response to
      abiotic stresses. Comparative proteomic analysis showed that the level of RPN6
      protein, a non-ATPase subunit of the 26S proteasome complex, was significantly
      reduced in 35SCaPUB1 seedlings as compared to the wild type. Pull-down and
      ubiquitination assays demonstrated that RPN6 interacted physically with CaPUB1
      and was ubiquitinated in a CaPUB1-dependent manner in vitro. Although the
      physiological function of CaPUB1 is not yet clear, there are several
      possibilities for its involvement in a subset of physiological responses to
      counteract dehydration and high-salinity stresses in transgenic Arabidopsis
      seedlings.

PMID- 17041031
TI  - Interactions between MUR10/CesA7-dependent secondary cellulose biosynthesis and
      primary cell wall structure.
AB  - Primary cell walls are deposited and remodeled during cell division and
      expansion. Secondary cell walls are deposited in specialized cells after the
      expansion phase. It is presently unknown whether and how these processes are
      interrelated. The Arabidopsis (Arabidopsis thaliana) MUR10 gene is required for
      normal primary cell wall carbohydrate composition in mature leaves as well as for
      normal plant growth, hypocotyl strength, and fertility. The overall sugar
      composition of young mur10 seedlings is not significantly altered; however, the
      relative proportion of pectin side chains is shifted toward an increase in 1 -->
      5-alpha-arabinan relative to 1 --> 4-beta-galactan. mur10 seedlings display
      reduced fucogalactosylation of tightly cell wall-bound xyloglucan. Expression
      levels of genes encoding either nucleotide sugar interconversion enzymes or
      glycosyl transferases, known to be involved in primary and secondary cell wall
      biosynthesis, are generally unaffected; however, the CesA7 transcript is
      specifically suppressed in the mur10-1 allele. The MUR10 locus is identical with
      the CesA7 gene, which encodes a cellulose catalytic subunit previously thought to
      be specifically involved in secondary cell wall formation. The xylem vessels in
      young mur10 hypocotyls are collapsed and their birefringence is lost. Moreover, a
      fucogalactosylated xyloglucan epitope is reduced and a 1 --> 5-alpha-arabinan
      epitope increased in every cell type in mur10 hypocotyls, including cells that do
      not deposit secondary walls. mur10 also displays altered distribution of an
      arabinogalactan-protein epitope previously associated with xylem differentiation
      and secondary wall thickening. This work indicates the existence of a mechanism
      that senses secondary cell wall integrity and controls biosynthesis or structural
      remodeling of primary cell walls and cellular differentiation.

PMID- 17041032
TI  - The liverwort Marchantia polymorpha expresses orthologs of the fungal Agaricus
      bisporus agglutinin family.
AB  - A lectin different from the previously described mannose-binding agglutinins has
      been isolated from the liverwort Marchantia polymorpha. Biochemical
      characterization of the purified lectin combined with the data from earlier
      transcriptome analyses demonstrated that the novel M. polymorpha agglutinin is
      not related to any of the known plant lectin families, but closely resembles the
      Agaricus bisporus-type lectins, which hitherto have been found exclusively in
      fungi. Immunolocalization studies confirmed that lectin is exclusively associated
      with plant cells, ruling out the possibility of a fungal origin. Extensive
      screening of publicly accessible databases confirmed that, apart from fungi, the
      occurrence of A. bisporus-type lectins is confined to M. polymorpha and the moss
      Tortula ruralis. Expression of a typical fungal protein in a liverwort and a moss
      raises the question of the origin of the corresponding genes. Regardless of the
      evolutionary origin, the presence of a functional A. bisporus lectin ortholog in
      M. polymorpha provides evidence for the expression of an additional carbohydrate
      binding domain in Viridiplantae.

PMID- 17041033
TI  - Embolism formation during freezing in the wood of Picea abies.
AB  - Freeze-thaw events can cause embolism in plant xylem. According to classical
      theory, gas bubbles are formed during freezing and expand during thawing.
      Conifers have proved to be very resistant to freeze-thaw induced embolism,
      because bubbles in tracheids are small and redissolve during thawing. In
      contrast, increasing embolism rates upon consecutive freeze-thaw events were
      observed that cannot be explained by the classical mechanism. In this study,
      embolism formation during freeze-thaw events was analyzed via ultrasonic and Cryo
      scanning electron microscope techniques. Twigs of Picea abies L. Karst. were
      subjected to up to 120 freeze-thaw cycles during which ultrasonic acoustic
      emissions, xylem temperature, and diameter variations were registered. In
      addition, the extent and cross-sectional pattern of embolism were analyzed with
      staining experiments and Cryo-scanning electron microscope observations. Embolism
      increased with the number of freeze-thaw events in twigs previously dehydrated to
      a water potential of -2.8 MPa. In these twigs, acoustic emissions were
      registered, while saturated twigs showed low, and totally dehydrated twigs showed
      no, acoustic activity. Acoustic emissions were detected only during the freezing
      process. This means that embolism was formed during freezing, which is in
      contradiction to the classical theory of freeze-thaw induced embolism. The
      clustered pattern of embolized tracheids in cross sections indicates that air
      spread from a dysfunctional tracheid to adjacent functional ones. We hypothesize
      that the low water potential of the growing ice front led to a decrease of the
      potential in nearby tracheids. This may result in freezing-induced air seeding.

PMID- 17041034
TI  - Nuclear magnetic resonance spectroscopy-based metabolite profiling of transgenic
      tomato fruit engineered to accumulate spermidine and spermine reveals enhanced
      anabolic and nitrogen-carbon interactions.
AB  - Polyamines are ubiquitous aliphatic amines that have been implicated in myriad
      processes, but their precise biochemical roles are not fully understood. We have
      carried out metabolite profiling analyses of transgenic tomato (Solanum
      lycopersicum) fruit engineered to accumulate the higher polyamines spermidine
      (Spd) and spermine (Spm) to bring an insight into the metabolic processes that
      Spd/Spm regulate in plants. NMR spectroscopic analysis revealed distinct
      metabolite trends in the transgenic and wild-type/azygous fruits ripened off the
      vine. Distinct metabolites (glutamine, asparagine, choline, citrate, fumarate,
      malate, and an unidentified compound A) accumulated in the red transgenic fruit,
      while the levels of valine, aspartic acid, sucrose, and glucose were
      significantly lower as compared to the control (wild-type and azygous) red fruit.
      The levels of isoleucine, glucose, gamma-aminobutyrate, phenylalanine, and
      fructose remained similar in the nontransgenic and transgenic fruits. Statistical
      treatment of the metabolite variables distinguished the control fruits from the
      transgenic fruit and provided credence to the pronounced, differential metabolite
      profiles seen during ripening of the transgenic fruits. The pathways involved in
      the nitrogen sensing/signaling and carbon metabolism seem preferentially
      activated in the high Spd/Spm transgenics. The metabolite profiling analysis
      suggests that Spd and Spm are perceived as nitrogenous metabolites by the fruit
      cells, which in turn results in the stimulation of carbon sequestration. This is
      seen manifested in higher respiratory activity and up-regulation of
      phosphoenolpyruvate carboxylase and NADP-dependent isocitrate dehydrogenase
      transcripts in the transgenic fruit compared to controls, indicating high
      metabolic status of the transgenics even late in fruit ripening.

PMID- 17041035
TI  - Analysis of proline reduction in the nosocomial pathogen Clostridium difficile.
AB  - Clostridium difficile, a proteolytic strict anaerobe, has emerged as a clinically
      significant nosocomial pathogen in recent years. Pathogenesis is due to the
      production of lethal toxins, A and B, members of the large clostridial cytotoxin
      family. Although it has been established that alterations in the amino acid
      content of the growth medium affect toxin production, the molecular mechanism for
      this observed effect is not yet known. Since there is a paucity of information on
      the amino acid fermentation pathways used by this pathogen, we investigated
      whether Stickland reactions might be at the heart of its bioenergetic pathways.
      Growth of C. difficile on Stickland pairs yielded large increases in cell density
      in a limiting basal medium, demonstrating that these reactions are tied to ATP
      production. Selenium supplementation was required for this increase in cell
      yield. Analysis of genome sequence data reveals genes encoding the protein
      components of two key selenoenzyme reductases, glycine reductase and d-proline
      reductase (PR). These selenoenzymes were expressed upon the addition of the
      corresponding Stickland acceptor (glycine, proline, or hydroxyproline).
      Purification of the selenoenzyme d-proline reductase revealed a mixed complex of
      PrdA and PrdB (SeCys-containing) proteins. PR utilized only d-proline but not l
      hydroxyproline, even in the presence of an expressed and purified proline
      racemase. PR was found to be independent of divalent cations, and zinc was a
      potent inhibitor of PR. These results show that Stickland reactions are key to
      the growth of C. difficile and that the mechanism of PR may differ significantly
      from that of previously studied PR from nonpathogenic species.

PMID- 17041036
TI  - Role of RelGsu in stress response and Fe(III) reduction in Geobacter
      sulfurreducens.
AB  - Geobacter species are key members of the microbial community in many subsurface
      environments in which dissimilatory metal reduction is an important process. The
      genome of Geobacter sulfurreducens contains a gene designated rel(Gsu), which
      encodes a RelA homolog predicted to catalyze both the synthesis and the
      degradation of guanosine 3',5'-bispyrophosphate (ppGpp), a regulatory molecule
      that signals slow growth in response to nutrient limitation in bacteria. To
      evaluate the physiological role of Rel(Gsu) in G. sulfurreducens, a rel(Gsu)
      mutant was constructed and characterized, and ppGpp levels were monitored under
      various conditions in both the wild-type and rel(Gsu) mutant strains. In the wild
      type strain, ppGpp and ppGp were produced in response to acetate and nitrogen
      deprivation, whereas exposure to oxygen resulted in an accumulation of ppGpp
      alone. Neither ppGpp nor ppGp could be detected in the rel(Gsu) mutant. The
      rel(Gsu) mutant consistently grew to a higher cell density than the wild type in
      acetate-fumarate medium and was less tolerant of oxidative stress than the wild
      type. The capacity for Fe(III) reduction was substantially diminished in the
      mutant. Microarray and quantitative reverse transcription-PCR analyses indicated
      that during stationary-phase growth, protein synthesis genes were up-regulated in
      the rel(Gsu) mutant and genes involved in stress responses and electron
      transport, including several implicated in Fe(III) reduction, were down-regulated
      in the mutant. The results are consistent with a role for Rel(Gsu) in regulating
      growth, stress responses, and Fe(III) reduction in G. sulfurreducens under
      conditions likely to be prevalent in subsurface environments.

PMID- 17041037
TI  - Genome sequence of Avery's virulent serotype 2 strain D39 of Streptococcus
      pneumoniae and comparison with that of unencapsulated laboratory strain R6.
AB  - Streptococcus pneumoniae (pneumococcus) is a leading human respiratory pathogen
      that causes a variety of serious mucosal and invasive diseases. D39 is an
      historically important serotype 2 strain that was used in experiments by Avery
      and coworkers to demonstrate that DNA is the genetic material. Although isolated
      nearly a century ago, D39 remains extremely virulent in murine infection models
      and is perhaps the strain used most frequently in current studies of pneumococcal
      pathogenesis. To date, the complete genome sequences have been reported for only
      two S. pneumoniae strains: TIGR4, a recent serotype 4 clinical isolate, and
      laboratory strain R6, an avirulent, unencapsulated derivative of strain D39. We
      report here the genome sequences and new annotation of two different isolates of
      strain D39 and the corrected sequence of strain R6. Comparisons of these three
      related sequences allowed deduction of the likely sequence of the D39 progenitor
      and mutations that arose in each isolate. Despite its numerous repeated sequences
      and IS elements, the serotype 2 genome has remained remarkably stable during
      cultivation, and one of the D39 isolates contains only five relatively minor
      mutations compared to the deduced D39 progenitor. In contrast, laboratory strain
      R6 contains 71 single-base-pair changes, six deletions, and four insertions and
      has lost the cryptic pDP1 plasmid compared to the D39 progenitor strain. Many of
      these mutations are in or affect the expression of genes that play important
      roles in regulation, metabolism, and virulence. The nature of the mutations that
      arose spontaneously in these three strains, the relative global transcription
      patterns determined by microarray analyses, and the implications of the D39
      genome sequences to studies of pneumococcal physiology and pathogenesis are
      presented and discussed.

PMID- 17041038
TI  - Characterization of the Moraxella catarrhalis opa-like protein, OlpA, reveals a
      phylogenetically conserved family of outer membrane proteins.
AB  - Moraxella catarrhalis is a human-restricted pathogen that can cause respiratory
      tract infections. In this study, we identified a previously uncharacterized 24
      kDa outer membrane protein with a high degree of similarity to Neisseria Opa
      protein adhesins, with a predicted beta-barrel structure consisting of eight
      antiparallel beta-sheets with four surface-exposed loops. In striking contrast to
      the antigenically variable Opa proteins, the M. catarrhalis Opa-like protein
      (OlpA) is highly conserved and constitutively expressed, with 25 of 27 strains
      corresponding to a single variant. Protease treatment of intact bacteria and
      isolation of outer membrane vesicles confirm that the protein is surface exposed
      yet does not bind host cellular receptors recognized by neisserial Opa proteins.
      Genome-based analyses indicate that OlpA and Opa derive from a conserved family
      of proteins shared by a broad array of gram-negative bacteria.

PMID- 17041039
TI  - Kinase activity of overexpressed HipA is required for growth arrest and multidrug
      tolerance in Escherichia coli.
AB  - Overexpression of the HipA protein of the HipBA toxin/antitoxin module leads to
      multidrug tolerance in Escherichia coli. HipA is a "toxin" that causes reversible
      dormancy, whereas HipB is an antitoxin that binds HipA and acts as a
      transcriptional repressor of the hipBA operon. Comparative sequence analysis
      shows that HipA is a member of the phosphatidylinositol 3/4-kinase superfamily.
      The kinase activity of HipA was examined. HipA was autophosphorylated in the
      presence of ATP in vitro, and the purified protein appeared to carry a single
      phosphate group on serine 150. Thus, HipA is a serine kinase that is at least
      partially phosphorylated in vivo. Overexpression of HipA caused inhibition of
      cell growth and increase in persister formation. Replacing conserved aspartate
      309 in the conserved kinase active site or aspartate 332 in the Mg2+-binding site
      with glutamine produced mutant proteins that lost the ability to stop cellular
      growth upon overexpression. Replacing serine 150 with alanine yielded a similarly
      inactive protein. The mutant proteins were then examined for their ability to
      increase antibiotic tolerance. Cells overexpressing wild-type HipA were highly
      tolerant to cefotaxime, a cell wall synthesis inhibitor, to ofloxacin, a
      fluoroquinolone inhibitor of DNA gyrase, and to topoisomerase IV and were almost
      completely resistant to killing by mitomycin C, which forms DNA adducts. The
      mutant proteins did not protect cells from cefotaxime or ofloxacin and had an
      impaired ability to protect from mitomycin C. Taken together, these results
      suggest that the protein kinase activity of HipA is essential for persister
      formation.

PMID- 17041040
TI  - Analysis of the roles of FlgP and FlgQ in flagellar motility of Campylobacter
      jejuni.
AB  - Flagellar motility is an important determinant of Campylobacter jejuni that is
      required for promoting interactions with various hosts to promote gastroenteritis
      in humans or commensal colonization of many animals. In a previous study, we
      identified a nonmotile mutant of C. jejuni 81-176 with a transposon insertion in
      Cj1026c, but verification of the role of the encoded protein in motility was not
      determined. In this study, we have determined that Cj1026c and the gene
      immediately downstream, Cj1025c (here annotated as flgP and flgQ, respectively),
      are both required for motility of C. jejuni but not for flagellar biosynthesis.
      FlgP and FlgQ are not components of the transcriptional regulatory cascades to
      activate sigma(28)- or sigma(54)-dependent expression of flagellar genes. In
      addition, expression of flgP and flgQ is not largely dependent on sigma(28) or
      sigma(54). Immunblot analyses revealed that the majority of FlgP in C. jejuni is
      associated with the outer membrane. However, in the absence of FlgQ, the amounts
      of FlgP in the outer membrane of C. jejuni are greatly reduced, suggesting that
      FlgQ may be required for localization or stability of FlgP at this location. This
      study provides insight into features of FlgP and FlgQ, two proteins with
      previously undefined functions that are required for the larger, multicomponent
      flagellar system of C. jejuni that is necessary for motility.

PMID- 17041041
TI  - Agrobacterium tumefaciens soxR is involved in superoxide stress protection and
      also directly regulates superoxide-inducible expression of itself and a target
      gene.
AB  - Inactivation of Agrobacterium tumefaciens soxR increases sensitivity to
      superoxide generators. soxR expression is highly induced by superoxide stress and
      is autoregulated. SoxR also directly regulates the superoxide-inducible
      expression of atu5152. Taken together, the physiological role of soxR and the
      mechanism by which it regulates expression of target genes make the A.
      tumefaciens SoxR system different from other bacterial systems.

PMID- 17041042
TI  - Staphylococcus aureus IsdB is a hemoglobin receptor required for heme iron
      utilization.
AB  - The pathogenesis of human infections caused by the gram-positive microbe
      Staphylococcus aureus has been previously shown to be reliant on the acquisition
      of iron from host hemoproteins. The iron-regulated surface determinant system
      (Isd) encodes a heme transport apparatus containing three cell wall-anchored
      proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface
      and hence have the potential to interact with human hemoproteins. Here we report
      that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but
      not hemopexin, as iron sources for bacterial growth. We demonstrate that
      staphylococci capture hemoglobin on the bacterial surface via IsdB and that
      inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin
      binding to the staphylococcal cell wall and impairs the ability of S. aureus to
      utilize hemoglobin as an iron source. Stable-isotope-tracking experiments
      revealed removal of heme iron from hemoglobin and transport of this compound into
      staphylococci. Importantly, mutants lacking isdB, but not isdH, display a
      reduction in virulence in a murine model of abscess formation. Thus, IsdB
      mediated scavenging of iron from hemoglobin represents an important virulence
      strategy for S. aureus replication in host tissues and for the establishment of
      persistent staphylococcal infections.

PMID- 17041043
TI  - Molecular evolution of the H-NS protein: interaction with Hha-like proteins is
      restricted to enterobacteriaceae.
AB  - We show here that chromosomal hha-like genes are restricted to the
      Enterobacteriaceae. The H-NS N-terminal domain of members of this family includes
      an unaltered seven-amino-acid sequence located between helixes 1 and 2, termed
      the Hha signature, that contains key residues for H-NS-Hha interaction.

PMID- 17041044
TI  - Proteolytic processing is not essential for multiple functions of the Escherichia
      coli autotransporter adhesin involved in diffuse adherence (AIDA-I).
AB  - The Escherichia coli adhesin involved in diffuse adherence (AIDA-I), like many
      other autotransporter proteins, is released in the periplasm as a proprotein
      undergoing proteolytic processing after its translocation across the outer
      membrane. The proprotein is cleaved into a membrane-embedded fragment, AIDAc, and
      an extracellular fragment, the mature AIDA-I adhesin. The latter remains
      noncovalently associated with the outer membrane and can be released by heat
      treatment. The mechanism of cleavage of the proprotein and its role in the
      functionality of AIDA-I are not understood. Here, we show that cleavage is
      independent of the amount of AIDA-I in the outer membrane, suggesting an
      intramolecular autoproteolytic mechanism or a cleavage mediated by an unknown
      protease. We show that the two fragments, mature AIDA-I and AIDAc, can be
      cosolubilized and copurified in a folded and active conformation. We observed
      that the release by heat treatment results from the unfolding of AIDA-I and that
      the interaction of AIDA-I with AIDAc seems to be disturbed only by denaturation.
      We constructed an uncleavable point mutant of AIDA-I, where a serine of the
      cleavage site was changed into a leucine, and showed that adhesion,
      autoaggregation, and biofilm formation mediated by the mutant are
      indistinguishable from the wild-type levels. Lastly, we show that both proteins
      can mediate the invasion of cultured epithelial cells. Taken together, our
      experiments suggest that the proteolytic processing of AIDA-I plays a minor role
      in the functionality of this protein.

PMID- 17041045
TI  - Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis.
AB  - Pseudomonas aeruginosa is a human opportunistic pathogen that chronically infects
      the lungs of cystic fibrosis patients and is the leading cause of morbidity and
      mortality of people afflicted with this disease. A striking correlation between
      mutagenesis and the persistence of P. aeruginosa has been reported. In other well
      studied organisms, error-prone replication by Y family DNA polymerases
      contributes significantly to mutagenesis. Based on an analysis of the PAO1 genome
      sequence, P. aeruginosa contains a single Y family DNA polymerase encoded by the
      dinB gene. As part of an effort to understand the mechanisms of mutagenesis in P.
      aeruginosa, we have cloned the dinB gene of P. aeruginosa and utilized a
      combination of genetic and biochemical approaches to characterize the activity
      and regulation of the P. aeruginosa DinB protein (DinB(Pa)). Our results indicate
      that DinB(Pa) is a distributive DNA polymerase that lacks intrinsic proofreading
      activity in vitro. Modest overexpression of DinB(Pa) from a plasmid conferred a
      mutator phenotype in both Escherichia coli and P. aeruginosa. An examination of
      this mutator phenotype indicated that DinB(Pa) has a propensity to promote C-->A
      transversions and -1 frameshift mutations within poly(dGMP) and poly(dAMP) runs.
      The characterization of lexA+ and DeltalexA::aacC1 P. aeruginosa strains,
      together with in vitro DNA binding assays utilizing cell extracts or purified P.
      aeruginosa LexA protein (LexA(Pa)), indicated that the transcription of the dinB
      gene is regulated as part of an SOS-like response. The deletion of the dinB(Pa)
      gene sensitized P. aeruginosa to nitrofurazone and 4-nitroquinoline-1-oxide,
      consistent with a role for DinB(Pa) in translesion DNA synthesis over N2-dG
      adducts. Finally, P. aeruginosa exhibited a UV-inducible mutator phenotype that
      was independent of dinB(Pa) function and instead required polA and polC, which
      encode DNA polymerase I and the second DNA polymerase III enzyme, respectively.
      Possible roles of the P. aeruginosa dinB, polA, and polC gene products in
      mutagenesis are discussed.

PMID- 17041046
TI  - Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant
      cells in Pseudomonas aeruginosa biofilms.
AB  - During Pseudomonas aeruginosa flow cell biofilm development, the cell population
      differentiates into a nonmotile subpopulation which forms microcolonies and a
      migrating subpopulation which eventually colonizes the top of the microcolonies,
      resulting in the development of mushroom-shaped multicellular structures. The cap
      forming subpopulation was found to develop tolerance to membrane-targeting
      antimicrobial agents, such as the cyclic cationic peptide colistin and the
      detergent sodium dodecyl sulfate. The stalk-forming subpopulation, on the other
      hand, was sensitive to the membrane-targeting antibacterial agents. All biofilm
      associated cells were sensitive to the antibacterial agents when tested in
      standard plate assays. A mutation eliminating the production of type IV pili, and
      hence surface-associated motility, prevented the formation of regular mushroom
      shaped structures in the flow cell biofilms, and the development of tolerance to
      the antimicrobial agents was found to be affected as well. Mutations in genes
      interfering with lipopolysaccharide modification (pmr) eliminated the biofilm
      associated colistin tolerance phenotype. Experiments with a PAO1 strain harboring
      a pmr-gfp fusion showed that only the cap-forming subpopulation in biofilms
      treated with colistin expresses the pmr operon. These results suggest that
      increased antibiotic tolerance in biofilms may be a consequence of
      differentiation into distinct subpopulations with different phenotypic
      properties.

PMID- 17041047
TI  - High-affinity binding of the staphylococcal HarA protein to haptoglobin and
      hemoglobin involves a domain with an antiparallel eight-stranded beta-barrel
      fold.
AB  - Iron scavenging from the host is essential for the growth of pathogenic bacteria.
      In this study, we further characterized two staphylococcal cell wall proteins
      previously shown to bind hemoproteins. HarA and IsdB harbor homologous ligand
      binding domains, the so called NEAT domain (for "near transporter") present in
      several surface proteins of gram-positive pathogens. Surface plasmon resonance
      measurements using glutathione S-transferase (GST)-tagged HarAD1, one of the
      ligand binding domains of HarA, and GST-tagged full-length IsdB proteins
      confirmed high-affinity binding to hemoglobin and haptoglobin-hemoglobin
      complexes with equilibrium dissociation constants (K(D)) of 5 to 50 nM.
      Haptoglobin binding could be detected only with HarA and was in the low
      micromolar range. In order to determine the fold of this evolutionarily conserved
      ligand binding domain, the untagged HarAD1 protein was subjected to nuclear
      magnetic resonance spectroscopy, which revealed an eight-stranded, purely
      antiparallel beta-barrel with the strand order (-beta1 -beta2 -beta3 -beta6 
      beta5 -beta4 -beta7 -beta8), forming two Greek key motifs. Based on structural
      homology searches, the topology of the HarAD1 domain resembles that of the
      immunoglobulin (Ig) fold family, whose members are involved in protein-protein
      interactions, but with distinct structural features. Therefore, we consider that
      the HarAD1/NEAT domain fold is a novel variant of the Ig fold that has not yet
      been observed in other proteins.

PMID- 17041048
TI  - NrrA directly regulates expression of hetR during heterocyst differentiation in
      the cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120
      requires NtcA, the global nitrogen regulator in cyanobacteria, and HetR, the
      master regulator of heterocyst differentiation. Expression of hetR is upregulated
      by nitrogen deprivation, and its upregulation depends on NtcA. However, it has
      not yet been revealed how NtcA regulates the expression of hetR. In the
      experiments presented here, it was confirmed that NrrA (All4312), a nitrogen
      responsive response regulator, was required for the upregulation of hetR. The use
      of the nitrogen-responsive transcription initiation sites (TISs) for the hetR
      gene depended upon NrrA. NrrA bound specifically to the region upstream of TISs
      located at positions -728 and -696 in vitro. Overexpression of nrrA resulted in
      enhanced hetR expression and heterocyst formation. A molecular regulatory cascade
      is proposed whereby NtcA upregulates the expression of nrrA upon limitation of
      combined nitrogen in the medium and then NrrA upregulates the expression of hetR,
      leading to heterocyst differentiation.

PMID- 17041049
TI  - BadM is a transcriptional repressor and one of three regulators that control
      benzoyl coenzyme A reductase gene expression in Rhodopseudomonas palustris.
AB  - The rate-limiting enzyme of anaerobic benzoate degradation by Rhodopseudomonas
      palustris, benzoyl coenzyme A (CoA) reductase, is highly sensitive to oxygen, and
      its synthesis is tightly regulated. We determined that a previously unknown gene
      in the benzoate gene cluster, badM, encodes a transcriptional repressor of
      benzoyl-CoA reductase gene expression. BadM controls gene expression from the
      benzoyl-CoA reductase promoter in concert with two previously described
      transcriptional activators.

PMID- 17041050
TI  - Inactivation of Lgt allows systematic characterization of lipoproteins from
      Listeria monocytogenes.
AB  - Lipoprotein anchoring in bacteria is mediated by the prolipoprotein
      diacylglyceryl transferase (Lgt), which catalyzes the transfer of a
      diacylglyceryl moiety to the prospective N-terminal cysteine of the mature
      lipoprotein. Deletion of the lgt gene in the gram-positive pathogen Listeria
      monocytogenes (i) impairs intracellular growth of the bacterium in different
      eukaryotic cell lines and (ii) leads to increased release of lipoproteins into
      the culture supernatant. Comparative extracellular proteome analyses of the EGDe
      wild-type strain and the Delta lgt mutant provided systematic insight into the
      relative expression of lipoproteins. Twenty-six of the 68 predicted lipoproteins
      were specifically released into the extracellular proteome of the Delta lgt
      strain, and this proved that deletion of lgt is an excellent approach for
      experimental verification of listerial lipoproteins. Consequently, we generated
      Delta lgt Delta prfA double mutants to detect lipoproteins belonging to the main
      virulence regulon that is controlled by PrfA. Overall, we identified three
      lipoproteins whose extracellular levels are regulated and one lipoprotein that is
      posttranslationally modified depending on PrfA. It is noteworthy that in contrast
      to previous studies of Escherichia coli, we unambiguously demonstrated that
      lipidation by Lgt is not a prerequisite for activity of the lipoprotein-specific
      signal peptidase II (Lsp) in Listeria.

PMID- 17041051
TI  - Group B streptococcal pilus proteins contribute to adherence to and invasion of
      brain microvascular endothelial cells.
AB  - Surface filamentous structures known as pili have been discovered recently in the
      gram-positive streptococcal pathogens that cause invasive disease in humans,
      including group B Streptococcus (GBS). We show that two GBS proteins involved in
      pilus formation, encoded by pilA and pilB, also facilitate the interaction of
      this important agent of central nervous system infection with endothelial cells
      of the human blood-brain barrier.

PMID- 17041052
TI  - Expression of the pyr operon of Lactobacillus plantarum is regulated by inorganic
      carbon availability through a second regulator, PyrR2, homologous to the
      pyrimidine-dependent regulator PyrR1.
AB  - Inorganic carbon (IC), such as bicarbonate or carbon dioxide, stimulates the
      growth of Lactobacillus plantarum. At low IC levels, one-third of natural
      isolated L. plantarum strains are nutritionally dependent on exogenous arginine
      and pyrimidine, a phenotype previously defined as high-CO2-requiring (HCR)
      prototrophy. IC enrichment significantly decreased the amounts of the enzymes in
      the pyrimidine biosynthetic pathway encoded by the pyrR1BCAa1Ab1DFE operon, as
      demonstrated by proteomic analysis. Northern blot and reverse transcription-PCR
      experiments demonstrated that IC levels regulated pyr genes mainly at the level
      of transcription or RNA stability. Two putative PyrR regulators with 62% amino
      acid identity are present in the L. plantarum genome. PyrR1 is an RNA-binding
      protein that regulates the pyr genes in response to pyrimidine availability by a
      mechanism of transcriptional attenuation. In this work, the role of PyrR2 was
      investigated by allelic gene replacement. Unlike the pyrR1 mutant, the DeltapyrR2
      strain acquired a demand for both pyrimidines and arginine unless bicarbonate or
      CO2 was present at high concentrations, which is known as an HCR phenotype.
      Analysis of the IC- and pyrimidine-mediated regulation in pyrR1 and pyrR2 mutants
      suggested that only PyrR2 positively regulates the expression levels of the pyr
      genes in response to IC levels but had no effect on pyrimidine-mediated
      repression. A model is proposed for the respective roles of PyrR1 and PyrR2 in
      the pyr regulon expression.

PMID- 17041053
TI  - 4-Chlorobenzoate uptake in Comamonas sp. strain DJ-12 is mediated by a tripartite
      ATP-independent periplasmic transporter.
AB  - The fcb gene cluster involved in the hydrolytic dehalogenation of 4
      chlorobenzoate is organized in the order fcbB-fcbA-fcbT1-fcbT2-fcbT3-fcbC in
      Comamonas sp. strain DJ-12. The genes are operonic and inducible with 4-chloro-,
      4-iodo-, and 4-bromobenzoate. The fcbT1, fcbT2, and fcbT3 genes encode a
      transporter in the secondary TRAP (tripartite ATP-independent periplasmic)
      family. An fcbT1T2T3 knockout mutant shows a much slower growth rate on 4
      chlorobenzoate compared to the wild type. 4-Chlorobenzoate is transported into
      the wild-type strain five times faster than into the fcbT1T2T3 knockout mutant.
      Transport of 4-chlorobenzoate shows significant inhibition by 4-bromo-, 4-iodo-,
      and 4-fluorobenzoate and mild inhibition by 3-chlorobenzoate, 2-chlorobenzoate, 4
      hydroxybenzoate, 3-hydroxybenzoate, and benzoate. Uptake of 4-chlorobenzoate is
      significantly inhibited by ionophores which collapse the proton motive force.

PMID- 17041055
TI  - Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for
      autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp.
AB  - Autotrophic members of the Sulfolobales (Crenarchaeota) contain acetyl-coenzyme A
      (CoA)/propionyl-CoA carboxylase as the CO2 fixation enzyme and use a modified 3
      hydroxypropionate cycle to assimilate CO2 into cell material. In this central
      metabolic pathway malonyl-CoA, the product of acetyl-CoA carboxylation, is
      further reduced to 3-hydroxypropionate. Extracts of Metallosphaera sedula
      contained NADPH-specific malonyl-CoA reductase activity that was 10-fold up
      regulated under autotrophic growth conditions. Malonyl-CoA reductase was
      partially purified and studied. Based on N-terminal amino acid sequencing the
      corresponding gene was identified in the genome of the closely related
      crenarchaeum Sulfolobus tokodaii. The Sulfolobus gene was cloned and
      heterologously expressed in Escherichia coli, and the recombinant protein was
      purified and studied. The enzyme catalyzes the following reaction: malonyl-CoA +
      NADPH + H+ --> malonate-semialdehyde + CoA + NADP+. In its native state it is
      associated with small RNA. Its activity was stimulated by Mg2+ and thiols and
      inactivated by thiol-blocking agents, suggesting the existence of a cysteine
      adduct in the course of the catalytic cycle. The enzyme was specific for NADPH
      (Km = 25 microM) and malonyl-CoA (Km = 40 microM). Malonyl-CoA reductase has 38%
      amino acid sequence identity to aspartate-semialdehyde dehydrogenase, suggesting
      a common ancestor for both proteins. It does not exhibit any significant
      similarity with malonyl-CoA reductase from Chloroflexus aurantiacus. This shows
      that the autotrophic pathway in Chloroflexus and Sulfolobaceae has evolved
      convergently and that these taxonomic groups have recruited different genes to
      bring about similar metabolic processes.

PMID- 17041054
TI  - Characterization of a highly conserved island in the otherwise divergent
      Bordetella holmesii and Bordetella pertussis genomes.
AB  - The recently discovered pathogen Bordetella holmesii has been isolated from the
      airways and blood of diseased humans. Genetic events contributing to the
      emergence of B. holmesii are not understood, and its phylogenetic position among
      the bordetellae remains unclear. To address these questions, B. holmesii strains
      were analyzed by comparative genomic hybridization (CGH) to a Bordetella
      pertussis microarray and by multilocus sequence typing. Both methods indicated
      substantial sequence divergence between B. pertussis and B. holmesii. However,
      CGH identified a putative pathogenicity island of 66 kb that is highly conserved
      between these species and contains several IS481 elements that may have been
      laterally transferred from B. pertussis to B. holmesii. This island contains,
      among other genes, a functional, iron-regulated locus encoding the biosynthesis,
      export, and uptake of the siderophore alcaligin. The acquisition of this genomic
      island by B. holmesii may have significantly contributed to its emergence as a
      human pathogen. Horizontal gene transfer between B. pertussis and B. holmesii may
      also explain the unusually high sequence identity of their 16S rRNA genes.

PMID- 17041056
TI  - The UreEF fusion protein provides a soluble and functional form of the UreF
      urease accessory protein.
AB  - Four accessory proteins (UreD, UreE, UreF, and UreG) are typically required to
      form the nickel-containing active site in the urease apoprotein (UreABC). Among
      the accessory proteins, UreD and UreF have been elusive targets for biochemical
      and structural characterization because they are not overproduced as soluble
      proteins. Using the best-studied urease system, in which the Klebsiella aerogenes
      genes are expressed in Escherichia coli, a translational fusion of ureE and ureF
      was generated. The UreEF fusion protein was overproduced as a soluble protein
      with a convenient tag involving the His-rich region of UreE. The fusion protein
      was able to form a UreD(EF)G-UreABC complex and to activate urease in vivo, and
      it interacted with UreD-UreABC in vitro to form a UreD(EF)-UreABC complex. While
      the UreF portion of UreEF is fully functional, the fusion significantly affected
      the role of the UreE portion by interrupting its dimerization and altering its
      metal binding properties compared to those of the wild-type UreE. Analysis of a
      series of UreEF deletion mutants revealed that the C terminus of UreF is required
      to form the UreD(EF)G-UreABC complex, while the N terminus of UreF is essential
      for activation of urease.

PMID- 17041057
TI  - Identification of a gene negatively affecting antibiotic production and
      morphological differentiation in Streptomyces coelicolor A3(2).
AB  - SC7A1 is a cosmid with an insert of chromosomal DNA from Streptomyces coelicolor
      A3(2). Its insertion into the chromosome of S. coelicolor strains caused a
      duplication of a segment of ca. 40 kb and delayed actinorhodin antibiotic
      production and sporulation, implying that SC7A1 carried a gene negatively
      affecting these processes. The subcloning of SC7A1 insert DNA resulted in the
      identification of the open reading frame SCO5582 as nsdA, a gene negatively
      affecting Streptomyces differentiation. The disruption of chromosomal nsdA caused
      the overproduction of spores and of three of four known S. coelicolor antibiotics
      of quite different chemical types. In at least one case (that of actinorhodin),
      this was correlated with premature expression of a pathway-specific regulatory
      gene (actII-orf4), implying that nsdA in the wild-type strain indirectly
      repressed the expression of the actinorhodin biosynthesis cluster. nsdA
      expression was up-regulated upon aerial mycelium initiation and was strongest in
      the aerial mycelium. NsdA has DUF921, a Streptomyces protein domain of unknown
      function and a conserved SXR site. A site-directed mutation (S458A) in this site
      in NsdA abolished its function. Blast searching showed that NsdA homologues are
      present in some Streptomyces genomes. Outside of streptomycetes, NsdA-like
      proteins have been found in several actinomycetes. The disruption of the nsdA
      like gene SCO4114 had no obvious phenotypic effects on S. coelicolor. The nsdA
      orthologue SAV2652 in S. avermitilis could complement the S. coelicolor nsdA-null
      mutant phenotype.

PMID- 17041058
TI  - Complete sequence analysis of novel plasmids from emetic and periodontal Bacillus
      cereus isolates reveals a common evolutionary history among the B. cereus-group
      plasmids, including Bacillus anthracis pXO1.
AB  - The plasmids of the members of the Bacillus cereus sensu lato group of organisms
      are essential in defining the phenotypic traits associated with pathogenesis and
      ecology. For example, Bacillus anthracis contains two plasmids, pXO1 and pXO2,
      encoding toxin production and encapsulation, respectively, that define this
      species pathogenic potential, whereas the presence of a Bt toxin-encoding plasmid
      defines Bacillus thuringiensis isolates. In this study the plasmids from B.
      cereus isolates that produce emetic toxin or are linked to periodontal disease
      were sequenced and analyzed. Two periodontal isolates examined contained almost
      identical approximately 272-kb plasmids, named pPER272. The emetic toxin
      producing isolate contained one approximately 270-kb plasmid, named pCER270,
      encoding the cereulide biosynthesis gene cluster. Comparative sequence analyses
      of these B. cereus plasmids revealed a high degree of sequence similarity to the
      B. anthracis pXO1 plasmid, especially in a putative replication region. These
      plasmids form a newly defined group of pXO1-like plasmids. However, these novel
      plasmids do not contain the pXO1 pathogenicity island, which in each instance is
      replaced by plasmid specific DNA. Plasmids pCER270 and pPER272 share regions that
      are not found in any other pXO1-like plasmids. Evolutionary studies suggest that
      these plasmids are more closely related to each other than to other identified B.
      cereus plasmids. Screening of a population of B. cereus group isolates revealed
      that pXO1-like plasmids are more often found in association with clinical
      isolates. This study demonstrates that the pXO1-like plasmids may define
      pathogenic B. cereus isolates in the same way that pXO1 and pXO2 define the B.
      anthracis species.

PMID- 17041059
TI  - Functional analysis of AtlA, the major N-acetylglucosaminidase of Enterococcus
      faecalis.
AB  - The major peptidoglycan hydrolase of Enterococcus faecalis, AtlA, has been
      identified, but its enzyme activity remains unknown. We have used tandem mass
      spectrometry analysis of peptidoglycan hydrolysis products obtained using the
      purified protein to show that AtlA is an N-acetylglucosaminidase. To gain insight
      into the regulation of its enzyme activity, the three domains of AtlA were
      purified alone or in combination following expression of truncated forms of the
      atlA gene in Escherichia coli or partial digestion of AtlA by proteinase K. The
      central domain of AtlA was catalytically active, but its activity was more than
      two orders of magnitude lower than that of the complete protein. Partial
      proteolysis of AtlA was detected in vivo: zymograms of E. faecalis extracts
      revealed two catalytically active protein bands of 62 and 72 kDa that were both
      absent in extracts from an atlA null mutant. Limited digestion of AtlA by
      proteinase K in vitro suggested that the proteolytic cleavage of AtlA in E.
      faecalis extracts corresponds to the truncation of the N-terminal domain, which
      is rich in threonine and glutamic acid residues. We show that the truncation of
      the N-terminal domain from recombinant AtlA has no impact on enzyme activity. The
      C-terminal domain of the protein, which contains six LysM modules bound to highly
      purified peptidoglycan, was required for optimal enzyme activity. These data
      indicate that AtlA is not produced as a proenzyme and that control of the AtlA
      glucosaminidase activity is likely to occur at the level of LysM-mediated binding
      to peptidoglycan.

PMID- 17041060
TI  - Abortive infection mechanisms and prophage sequences significantly influence the
      genetic makeup of emerging lytic lactococcal phages.
AB  - In this study, we demonstrated the remarkable genome plasticity of lytic
      lactococcal phages that allows them to rapidly adapt to the dynamic dairy
      environment. The lytic double-stranded DNA phage ul36 was used to sequentially
      infect a wild-type strain of Lactococcus lactis and two isogenic derivatives with
      genes encoding two phage resistance mechanisms, AbiK and AbiT. Four phage mutants
      resistant to one or both Abi mechanisms were isolated. Comparative analysis of
      their complete genomes, as well as morphological observations, revealed that
      phage ul36 extensively evolved by large-scale homologous and nonhomologous
      recombination events with the inducible prophage present in the host strain. One
      phage mutant exchanged as much as 79% of its genome compared to the core genome
      of ul36. Thus, natural phage defense mechanisms and prophage elements found in
      bacterial chromosomes contribute significantly to the evolution of the lytic
      phage population.

PMID- 17041061
TI  - N-acetylanthranilate amidase from Arthrobacter nitroguajacolicus Ru61a, an
      alpha/beta-hydrolase-fold protein active towards aryl-acylamides and -esters, and
      properties of its cysteine-deficient variant.
AB  - N-acetylanthranilate amidase (Amq), a 32.8-kDa monomeric amide hydrolase, is
      involved in quinaldine degradation by Arthrobacter nitroguajacolicus Ru61a.
      Sequence analysis and secondary structure predictions indicated that Amq is
      related to carboxylesterases and belongs to the alpha/beta-hydrolase-fold
      superfamily of enzymes; inactivation of (His(6)-tagged) Amq by
      phenylmethanesulfonyl fluoride and diethyl pyrocarbonate and replacement of
      conserved residues suggested a catalytic triad consisting of S155, E235, and
      H266. Amq is most active towards aryl-acetylamides and aryl-acetylesters.
      Remarkably, its preference for ring-substituted analogues was different for
      amides and esters. Among the esters tested, phenylacetate was hydrolyzed with
      highest catalytic efficiency (k(cat)/K(m) = 208 mM(-1) s(-1)), while among the
      aryl-acetylamides, o-carboxy- or o-nitro-substituted analogues were preferred
      over p-substituted or unsubstituted compounds. Hydrolysis by His(6)Amq of primary
      amides, lactams, N-acetylated amino acids, azocoll, tributyrin, and the
      acylanilide and urethane pesticides propachlor, propham, carbaryl, and isocarb
      was not observed; propanil was hydrolyzed with 1% N-acetylanthranilate amidase
      activity. The catalytic properties of the cysteine-deficient variant
      His(6)AmqC22A/C63A markedly differed from those of His(6)Amq. The replacements
      effected some changes in K(m)s of the enzyme and increased k(cat)s for most aryl
      acetylesters and some aryl-acetylamides by factors of about three to eight while
      decreasing k(cat) for the formyl analogue N-formylanthranilate by several orders
      of magnitude. Circular dichroism studies indicated that the cysteine-to-alanine
      replacements resulted in significant change of the overall fold, especially an
      increase in alpha-helicity of the cysteine-deficient protein. The conformational
      changes may also affect the active site and may account for the observed changes
      in kinetic properties.

PMID- 17041062
TI  - Regulation of Aggregatibacter (Actinobacillus) actinomycetemcomitans leukotoxin
      secretion by iron.
AB  - The gram-negative oral and systemic pathogen Aggregatibacter (Actinobacillus)
      actinomycetemcomitans produces a leukotoxin (LtxA) that is a member of the RTX
      (repeats in toxin) family of secreted bacterial toxins. We have recently shown
      that LtxA has the ability to lyse erythrocytes, which results in a beta-hemolytic
      phenotype on Columbia blood agar. To determine if LtxA is regulated by iron, we
      examined beta-hemolysis under iron-rich and iron-limiting conditions. Beta
      hemolysis was suppressed in the presence of FeCl3. In contrast, strong beta
      hemolysis occurred in the presence of the iron chelator deferoxamine. We found
      that secretion of LtxA was completely inhibited by free iron, but expression of
      ltxA was not regulated by iron. Free chromium, cobalt, and magnesium did not
      affect LtxA secretion. Other LtxA-associated genes were not regulated by iron.
      Thus, iron appears to play an important role in the regulation of LtxA secretion
      in A. actinomycetemcomitans in a manner independent of gene regulation.

PMID- 17041063
TI  - Membrane topology mapping of the Na+-pumping NADH: quinone oxidoreductase from
      Vibrio cholerae by PhoA-green fluorescent protein fusion analysis.
AB  - The membrane topologies of the six subunits of Na+-translocating NADH:quinone
      oxidoreductase (Na+-NQR) from Vibrio cholerae were determined by a combination of
      topology prediction algorithms and the construction of C-terminal fusions. Fusion
      expression vectors contained either bacterial alkaline phosphatase (phoA) or
      green fluorescent protein (gfp) genes as reporters of periplasmic and cytoplasmic
      localization, respectively. A majority of the topology prediction algorithms did
      not predict any transmembrane helices for NqrA. A lack of PhoA activity when
      fused to the C terminus of NqrA and the observed fluorescence of the green
      fluorescent protein C-terminal fusion confirm that this subunit is localized to
      the cytoplasmic side of the membrane. Analysis of four PhoA fusions for NqrB
      indicates that this subunit has nine transmembrane helices and that residue T236,
      the binding site for flavin mononucleotide (FMN), resides in the cytoplasm. Three
      fusions confirm that the topology of NqrC consists of two transmembrane helices
      with the FMN binding site at residue T225 on the cytoplasmic side. Fusion
      analysis of NqrD and NqrE showed almost mirror image topologies, each consisting
      of six transmembrane helices; the results for NqrD and NqrE are consistent with
      the topologies of Escherichia coli homologs YdgQ and YdgL, respectively. The
      NADH, flavin adenine dinucleotide, and Fe-S center binding sites of NqrF were
      localized to the cytoplasm. The determination of the topologies of the subunits
      of Na+-NQR provides valuable insights into the location of cofactors and
      identifies targets for mutagenesis to characterize this enzyme in more detail.
      The finding that all the redox cofactors are localized to the cytoplasmic side of
      the membrane is discussed.

PMID- 17041064
TI  - Serological survey of encephalomyocarditis virus infection in pigs in France.
AB  - Samples of serum from 76 gilts, 1440 sows, 1473 piglets and 3093 finishing pigs
      from 96 farrow-to-finish herds were tested for antibodies to encephalomyocarditis
      virus (EMCV) in microtitre serum neutralisation tests employing two strains of
      virus, one associated with myocarditis and the other with reproductive failure.
      The total seroprevalence of EMCV infection was 2.48 per cent. There was no
      significant difference between the seroprevalence of the reproductive failure
      strain (1.6 per cent) and the myocardial strain (1.85 per cent). The
      seroprevalence was higher in the gilts (6.57 per cent) and sows (5.13 per cent)
      than in the piglets (1 per cent) and finishing pigs (1.84 per cent), and the
      highest titres were observed in the sows (1:540) and finishing pigs (1:640). In
      the gilts, the difference in seroprevalence between the reproductive failure
      strain (3.95 per cent) and the myocardial strain (5.33 per cent) was wider than
      in the other groups.

PMID- 17041065
TI  - Skeletal deformities and mortality in grey herons (Ardea cinerea) at Besthorpe
      heronry, Nottinghamshire.
AB  - Dead and sick grey heron chicks with multiple fractures of the leg and wing bones
      and/or bone deformities have been reported at Besthorpe Nature Reserve heronry in
      north Nottinghamshire since 1996. Forty-five grey heron carcases were examined,
      35 from the Besthorpe colony and 10 from other colonies where bone disease was
      not known to occur. On the basis of the results of radiological studies,
      postmortem examinations, peripheral quantitative computed tomography scanning and
      four-point bending tests, it was concluded that the skeletal abnormalities were
      probably due to metabolic bone disease.

PMID- 17041066
TI  - Production of prolific microsheep by embryo transfer into large non-prolific
      sheep.
AB  - The Garole is a prolific breed of microsheep that possesses the FecB gene, which
      increases ovulation rate. The purpose of this study was to compare embryo
      production by multiple ovulation in seven Garole ewes with that in seven normal
      size, non-prolific Malpura ewes, and assess the influence of the large body size
      of Awassi crossbred recipient ewes on the birth-weight of Garole lambs. Oestrus
      was synchronised with two intramuscular injections of 7.5 mg prostaglandin
      F(2alpha) administered 10 days apart. The donor ewes were superovulated by the
      use of pregnant mare serum gonadotrophin and follicle-stimulating hormone. The
      onset and duration of oestrus were similar in both breeds. The Garole donors had
      higher total mean (se) ovarian responses (15.6 [3.6] v 9.1 [2.3]), ovulation rate
      (13.6 [3.1] v 8.4 [2.2]) and produced more transferable embryos (6.0 [3.5] v 4.0
      [0.9]) than the Malpura donors, but the differences were not statistically
      significant. The Garole lambs produced by embryo transfer were on average 57.8
      per cent heavier at birth than contemporary Garole lambs produced by natural
      mating.

PMID- 17041067
TI  - Evaluation of four manual tick-removal devices for dogs and cats.

PMID- 17041068
TI  - Multiple endocrine neoplasia-like syndrome in a horse.

PMID- 17041069
TI  - Isolation of EBLV-2 in a Daubenton's bat (Myotis daubentonii) found in
      Oxfordshire.

PMID- 17041070
TI  - MRSA in companion animals.

PMID- 17041071
TI  - Treatment for fear of fireworks in dogs.

PMID- 17041072
TI  - Modular RCVS certificates.

PMID- 17041073
TI  - Prologue: combining research and reason to make treatment decisions.

PMID- 17041074
TI  - Evidence-based practice: an examination of its ramifications for the practice of
      speech-language pathology.
AB  - PURPOSE: The purpose of this article is to consider some of the ramifications
      that arise when a discipline newly endorses evidence-based practice (EBP) as a
      primary guiding principle. Although EBP may appear straightforward, events
      experienced by peer disciplines that have preceded us in the implementation of
      EBP raise questions about defining acceptable forms of evidence for treatment
      effectiveness and efficacy, the potential roles of nonspecific or common factors,
      therapist quality in achieving therapy outcomes, and eventual applications of EBP
      that may overly confine which treatments are considered acceptable and
      reimbursable. METHOD: Through narrative review of the literature, the article
      examines valuable as well as controversial features of EBP in addition to
      obstacles that may impede the transition of evidence (research findings) to
      clinical practice. CONCLUSION: EBP is a valuable construct in ensuring quality of
      care. However, bridging between research evidence and clinical practice may
      require us to confront potentially difficult issues and establish thoughtful
      dialogue about best practices in fostering EBP itself.

PMID- 17041075
TI  - Evidence-based practice in communication disorders: progress not perfection.
AB  - PURPOSE: This commentary is written in response to a companion paper by Nan
      Bernstein Ratner (Evidence-Based Practice: An Examination of its Ramifications
      for the Practice of Speech-Language Pathology). METHOD: The comments reflect my
      experience as Vice President for Research and Technology of the American Speech
      Language-Hearing Association (ASHA). One of the responsibilities of the Vice
      President is to monitor the work of the Advisory Committee on Evidence-Based
      Practice. CONCLUSION: Evidence-based practice (EBP) is a challenging but
      attainable goal for audiology and speech-language pathology. Our professions have
      made rapid progress in developing the foundations for EBP. To be sure, a great
      deal of work remains to be done, but we have learned from the experiences of
      other professions and have built our own systems to support EBP.

PMID- 17041076
TI  - Treatment decisions for children with speech-sound disorders.
AB  - PURPOSE: In this article, I consider how research, clinical expertise, client
      values, a clinician's theoretical perspective, and service delivery
      considerations affect the decisions that clinicians make to treat children with
      speech-sound disorders (SSD). METHOD: After reviewing the research on
      phonological treatment, I discuss how a clinician's theoretical perspective
      influences goal selection. Five perspectives are considered: (a) normative; (b)
      bottom-up, discrete skill; (c) language-based; (d) broad-based; and (e)
      complexity-based. The literature on treatment efficiency is then considered,
      followed by a discussion of service delivery factors, client values, and
      clinician factors. IMPLICATIONS: I believe like M. Ylvisaker (2004) that
      treatment decisions are influenced the most by the changes that occur in client
      behaviors. These changes must, however, be experimentally validated, which is not
      always easy to do. M. Ylvisaker suggests that validation could take the form of
      trial therapy, diagnostic teaching, or dynamic assessment, but it may also be
      important to show that the treatment provided, not some other variable, was
      primarily responsible for the behavioral change (A. Tyler, personal
      communication, January 11, 2006).

PMID- 17041077
TI  - Commentary on "treatment decisions for children with speech-sound disorders":
      revisiting the past in EBP.
AB  - PURPOSE: This commentary, written in response to Alan Kamhi's paper, "Treatment
      Decisions for Children with Speech-Sound Disorders," further considers the "what"
      or goal selection process of decision making with the aim of efficiency-getting
      the most change in the shortest time. METHOD: My comments reflect a focus on the
      client values piece of the evidence-based practice (EBP) triad through validating
      treatment decisions for individual clients using generalization data. Such data
      are ideal for demonstrating change according to specific benchmarks and
      suggesting that treatment was responsible for this change. Consideration is also
      given to deficit profiles and their implications for long-term outcomes when
      validating the effects of treatment. CONCLUSION: Although the abundance of
      evidence suggests that a variety of treatment approaches are effective for
      children with speech-sound disorders, less is known about which are most
      efficient as compared to one another or for which specific children.
      Practitioners, however, are embracing EBP when they select a treatment by
      matching the research evidence with a client's profile, collect systematic data,
      and use those data to demonstrate that change is attributable to treatment.

PMID- 17041078
TI  - Evidence-based practice, response to intervention, and the prevention of reading
      difficulties.
AB  - PURPOSE: This article provides an evidence-based perspective on what school
      communities can do to lower the prevalence of reading difficulties among their
      pupils through preventive interventions. It also delineates the roles that speech
      language pathologists (SLPs) might play in these interventions. METHOD: This
      article is organized to first provide a broad overview of current directions in
      research, practice, and policy in educational interventions, with an emphasis on
      how the three are increasingly integrated to respond to evidence showing that
      American school children are underperforming in reading. Next, the concept of
      response to intervention (RTI) is described. RTI is an educational policy and
      practice that is grounded in the accumulated literature that focuses on how
      schools might better organize themselves to deliver multitiered reading
      interventions to reduce children's risk for reading disability. Last, this
      article provides three organizational principles that school-based professionals,
      including SLPs, might follow to deliver RTI interventions. IMPLICATIONS: This
      article provides an important and timely description of key concepts in the
      prevention of reading difficulties through proactive multitiered interventions.
      SLPs can draw on the suggestions presented here to inform their local efforts in
      implementing preventive literacy programs that are consistent with an RTI
      paradigm.

PMID- 17041079
TI  - The implications of RTI and EBP for SLPs: commentary on L. M. Justice.
AB  - PURPOSE: This commentary responds to Justice's article on response to
      intervention (RTI) and evidence-based practice (EBP) for reading instruction. The
      educational changes brought about by RTI and EBP provide an opportunity as well
      as a challenge for speech-language pathologists (SLPs) to make fundamental
      changes in service delivery. METHOD: In this article, I discuss how RTI will
      change who qualifies as reading disabled and who receives special reading
      instruction. I examine how RTI might change who qualifies and how they qualify
      for speech-language services. Finally, I consider what can be taken from EPB and
      RTI to improve speech-language service delivery. CONCLUSION: RTI has the
      potential to fundamentally change regular education and its interface with
      special education. If SLP clinicians, researchers, and policymakers recognize the
      possibilities, RTI could also significantly and positively impact educational
      speech-language pathology.

PMID- 17041080
TI  - Making evidence-based decisions about child language intervention in schools.
AB  - PURPOSE: The results of recent survey studies suggest that speech-language
      pathologists base most of their clinical decisions on information they were
      taught during their graduate programs, their clinical experience, and the
      opinions of colleagues (T. Wolf & J. Balderson, 2005; R. Zipoli & M. Kennedy,
      2005). This is contrary to the principles of evidence-based practice (EBP), in
      which clinical decisions arise from the integration of scientific evidence,
      clinician experience, and client needs. Our field's interest in EBP is relatively
      young. Currently, there are no published committee-derived EBP guidelines for
      providing language intervention services for children with language disorders.
      Until national or international organizations publish recommendations from EBP
      guideline writing panels, clinicians will need to make personal evidence-based
      decisions with relatively little assistance from outside sources. The purpose of
      this article is to summarize a seven-step process for making local EBP decisions.
      METHOD: The authors provide information about a method for forming clinical
      questions, finding relevant scientific studies, and evaluating those studies that
      requires relatively little time and few external resources. The authors also
      provide a system for integrating scientific evidence with their own expertise and
      training within the context of their employment settings. Finally, an example is
      provided to show clinicians how to use the evidence-based decision-making process
      to answer a clinical question about clinical methods for improving grammatical
      morphology in children with speech-language impairment. CONCLUSION: It is
      possible for clinicians to make time- and resource-efficient evidence-based
      decisions that integrate scientific evidence, clinical expertise, and student
      parent preferences.

PMID- 17041081
TI  - Commentary on "making evidence-based decisions about child language intervention
      in schools" by Gillam and Gillam.
AB  - PURPOSE: This paper is a personal reaction to Gillam and Gillam's treatise on
      evidence-based decision making in schools. This evaluation focuses principally on
      the costs and benefits of clinicians' search for external evidence, potential
      problems associated with efforts to grade that evidence, and the integration of
      this evidence with "internal" evidence related to specific children and their
      families, clinician preferences and experience, and the school setting. METHOD:
      Descriptive methods (that are not evidence-based) are used to evaluate critically
      Gillam and Gillam's proposals on the implementation of evidence-based practice
      (EBP) in schools. CONCLUSION: Early efforts to implement the plan for EBP
      illustrated by Gillam and Gillam are likely to be difficult, forcing clinicians
      to be flexible and patient. Nevertheless, if the plan is followed, it will result
      ultimately in improved speech-language pathology services in the schools and
      improved clinical research to support those services.

PMID- 17041082
TI  - Epilogue: some final thoughts on EBP.
AB  - PURPOSE: In this afterward, I will offer some final thoughts on this clinical
      forum by considering a central question of EBP--how experimental validation is
      defined--to illustrate the difficulty involved in implementing EBP. METHOD: The
      comments draw on critical reviews I have received on my article in this forum and
      conversations I have had with professional colleagues about EBP. CONCLUSION: Like
      most scientific constructs, EBP is open to different interpretations. At their
      worst, these differences have the potential to polarize clinical practice. The
      hope, however, as Kent and Fey have expressed, is that articles and commentaries
      such as these will serve as the basis for discussion and even argument among
      clinicians and researchers as we attempt to define a philosophy and
      implementation of EBP suited to our profession.

PMID- 17041083
TI  - Which orthodontic archwire sequence? A randomized clinical trial.
AB  - The aim of this study was to compare three orthodontic archwire sequences. One
      hundred and fifty-four 10- to 17-year-old patients were treated in three centres
      and randomly allocated to one of three groups: A = 0.016-inch nickel titanium
      (NiTi), 0.018 x 0.025-inch NiTi, and 0.019 x 0.025-inch stainless steel (SS); B =
      0.016-inch NiTi, 0.016-inch SS, 0.020-inch SS, and 0.019 x 0.025-inch SS; and C =
      0.016 x 0.022-inch copper (Cu) NiTi, 0.019 x 0.025-inch CuNiTi, and 0.019 x 0.025
      inch SS. At each archwire change and for each arch, the patients completed
      discomfort scores on a seven-point Likert scale at 4 hours, 24 hours, 3 days, and
      1 week. Time in days and the number of visits taken to reach a 0.019 x 0.025-inch
      SS working archwires were calculated. A periapical radiograph of the upper left
      central incisor was taken at the start of the treatment and after placement of
      the 0.019 x 0.025-inch SS wire so root resorption could be assessed. There were
      no statistically significant differences between archwire sequences A, B, or C
      for patient discomfort (P > 0.05) or root resorption (P = 0.58). The number of
      visits required to reach the working archwire was greater for sequence B than for
      A (P = 0.012) but this could not be explained by the increased number of
      archwires used in sequence B.

PMID- 17041084
TI  - The clinical features and aetiological basis of primary eruption failure.
AB  - Primary failure of eruption (PFE) is a poorly understood condition associated
      with tooth eruption failure. This investigation systematically reviews the
      literature, evaluates clinical features and associations with PFE, and describes
      five further cases. Publications were selected and identified as describing PFE
      when there was no identifiable aetiological factor contributing to eruption
      failure and no evidence of successful orthodontic extrusion of the affected tooth
      or teeth. A data abstraction form recorded the following additional information;
      subject age, gender, general health status, and teeth present. Eighteen
      publications were sourced that detailed at least one case of PFE in a manner
      conforming to the selection criteria; these papers included a total of 35
      individual cases, to which five previously unreported subjects were added. Within
      the whole sample of 40 cases, a total of 24 (60 per cent) were females and 16 (40
      per cent) males. First and second molar teeth were most commonly affected;
      incisors, canines, and premolars were also involved, but with a reduced
      individual frequency. There was no significant difference in incidence between
      the maxilla and mandible, or between left and right sides. A family history of
      eruption failure was found in almost 50 per cent of the sample, with eruption
      failure or ankylosis affecting at least one primary tooth, also a common finding.
      Within the 40 cases, hypodontia was present at levels higher than population
      norms. PFE appears to be a condition that predominantly affects the molar
      dentition. The increased frequency of hypodontia in affected individuals and
      common findings of a family history regarding tooth eruption problems suggests a
      significant genetic component to the aetiology of this rare condition.

PMID- 17041085
TI  - Orthognathic treatment: how much does it cost?
AB  - The aim of this multi-centre retrospective study was to assess the cost, and
      factors influencing the cost, of combined orthodontic and surgical treatment for
      dentofacial deformity. The sample, from the south-west of England, comprised 352
      subjects (109 males and 243 females) with an age range of 14 to 57 years treated
      in 11 hospital orthodontic units. Treatment costs were calculated for each
      subject by combining consumable costs with staff overhead and capital costs. The
      median total treatment cost was euro 6075.25 (interquartile range: euro 5139.41
      euro 7069.68). Out-patient costs comprised 43 per cent. The median orthodontic
      treatment costs were euro 1456.23 (interquartile range: euro 1283.73-euro
      1638.75). Orthodontic costs on average comprised 25 per cent of the total
      treatment cost. The cost of orthodontics for orthognathic patients in a hospital
      setting appears to represent excellent value for the state funded National Health
      Service in the United Kingdom.

PMID- 17041086
TI  - Tumor models for efficacy determination.
AB  - The first in vivo tumor models were developed in the mid-1960s. These models were
      mouse leukemia models grown as ascites. The growth pattern was like that of
      bacteria in vivo and therefore it was possible to apply similar mathematics of
      growth and response to these tumors as had been worked out for bacteria. Since
      the development of the murine leukemia models, investigators have devoted a large
      effort to modeling solid tumors in mice. There are now a variety of models
      including syngeneic mouse tumors and human tumor xenografts grown as s.c.
      nodules, syngeneic mouse tumors and human tumor xenografts grown in orthotopic
      sites, models of disseminated disease, "labeled" tumor models that can be
      visualized using varied technologies, and transgenic tumor models. Each of these
      types of models has advantages and disadvantages to the "drug hunter" searching
      for improved treatments.

PMID- 17041087
TI  - Developing gene expression signatures of pathway deregulation in tumors.
AB  - Recent advances in our understanding of cancer biology have led to the
      development of therapies targeting specific signaling pathways. Molecular
      targeting promises to improve our ability to predict who will respond by
      assessing the state of these targeted pathways in patients. However, a single
      pathway can be deregulated by multiple mechanisms, and for some pathways it may
      be difficult to assess activation state by analyzing a single oncogene or tumor
      suppressor. Therefore, developing gene expression signatures of pathway
      activation status using model systems or human tumor samples may enable a more
      reliable measurement of pathway activity. This review discusses recent advances
      in the identification of gene expression-based signatures of pathway deregulation
      and how this information may lead to improved therapeutic response prediction.

PMID- 17041088
TI  - Comparing Aurora A and Aurora B as molecular targets for growth inhibition of
      pancreatic cancer cells.
AB  - To address the increased need to understand the similarities and differences in
      targeting Aurora A or Aurora B for the treatment of cancer, we systematically
      evaluated the relative importance of Aurora A and/or Aurora B as molecular
      targets using antisense oligonucleotides. It was found that perturbations in
      Aurora A and Aurora B signaling result in growth arrest and apoptosis
      preferentially in cancer cells. The biological fingerprints of Aurora A and
      Aurora B inhibition were compared and contrasted in efforts to identify the
      superior therapeutic target. Due to the different biological responses, we
      conclude that each Aurora kinase should be treated as autonomous drug targets,
      which can be targeted independently or in combination. We observed no advantages
      to targeting both kinases simultaneously and feel that an Aurora A-targeted
      therapy may have some beneficial consequences over an Aurora B-targeted therapy,
      such as mitotic arrest and the rapid induction of apoptosis.

PMID- 17041089
TI  - Role of the ABCG2 drug transporter in the resistance and oral bioavailability of
      a potent cyclin-dependent kinase/Aurora kinase inhibitor.
AB  - Cell cycle kinase inhibitors have advanced into clinical trials in oncology. One
      such molecule, JNJ-7706621, is a broad-spectrum inhibitor of the cyclin-dependent
      kinases and Aurora kinases that mediate G(2)-M arrest and inhibits tumor growth
      in xenograft models. To determine the putative mechanisms of resistance to JNJ
      7706621 that might be encountered in the clinic, the human epithelial cervical
      carcinoma cell line (HeLa) was exposed to incrementally increasing concentrations
      of JNJ-7706621. The resulting resistant cell population, designated HeLa-6621,
      was 16-fold resistant to JNJ-7706621, cross-resistant to mitoxantrone (15-fold)
      and topotecan (6-fold), and exhibited reduced intracellular drug accumulation of
      JNJ-7706621. ABCG2 was highly overexpressed at both the mRNA ( approximately 163
      fold) and protein levels. The functional role of ABCG2 in mediating resistance to
      JNJ-7706621 was consistent with the following findings: (a) an ABCG2 inhibitor,
      fumitremorgin C, restored the sensitivity of HeLa-6621 cells to JNJ-7706621 and
      to mitoxantrone; (b) human embryonic kidney-293 cells transfected with ABCG2 were
      resistant to both JNJ-7706621 and mitoxantrone; and (c) resistant cells that were
      removed from the drug for 12 weeks and reverted to susceptibility to JNJ-7706621
      showed near-normal ABCG2 RNA levels. ABCG2 is likely to limit the bioavailability
      of JNJ-7706621 because oral administration of JNJ-7706621 to Bcrp (the murine
      homologue of ABCG2) knockout mice resulted in an increase in the plasma
      concentration of JNJ-7706621 compared with wild-type mice. These findings
      indicate that ABCG2 mediates the resistance to JNJ-7706621 and alters the
      absorption of the compound following administration.

PMID- 17041090
TI  - Differing effects of microtubule depolymerizing and stabilizing chemotherapeutic
      agents on t-SNARE-mediated apical targeting of prostate-specific membrane
      antigen.
AB  - Prostate-specific membrane antigen (PSMA) is a protein up-regulated in the vast
      majority of prostate cancers. Antibodies to PSMA have proved highly specific for
      prostate cancer cells, and the therapeutic potential of such antibodies is
      currently being assessed in clinical trials. We have previously shown that PSMA
      at the cell surface of polarized epithelial cells is predominantly expressed at
      the apical plasma membrane and that microtubule depolymerization abolishes apical
      PSMA targeting. In the current report, we implicate a functional role for a
      target membrane soluble N-ethylmaleimide-sensitive factor adaptor protein
      receptor, syntaxin 3, in the microtubule-dependent apical targeting of PSMA. PSMA
      and syntaxin 3 are similarly localized to the apical plasma membrane of the
      prostatic epithelium and Madin-Darby canine kidney cells. Introduction of a point
      mutation into syntaxin 3 abolishes its polarized distribution and causes PSMA to
      be targeted in a nonpolarized fashion. Additionally, treatment of polarized Madin
      Darby canine kidney cells with vinblastine, a microtubule depolymerizing
      chemotherapeutic agent, causes both syntaxin 3 and PSMA to redistribute in a
      nonpolarized fashion. However, following treatment with the microtubule
      stabilizing chemotherapeutic agent Taxotere, both syntaxin 3 and PSMA continue to
      localize in a polarized manner at the apical plasma membrane. Thus, microtubule
      depolymerizing and stabilizing chemotherapeutic drugs might exact similar
      cytotoxic effects but have disparate effects on protein targeting. This
      phenomenon might have important clinical implication, especially related to
      antibody-mediated immunotherapy, and could potentially be exploited for
      therapeutic benefit.

PMID- 17041091
TI  - Dimerization of CXCR4 in living malignant cells: control of cell migration by a
      synthetic peptide that reduces homologous CXCR4 interactions.
AB  - Chemokine receptor CXCR4 (CD184) may play a role in cancer metastasis and is
      known to form homodimers. However, it is not clear how transmembrane regions (TM)
      of CXCR4 and receptor homotypic interactions affect the function of CXCR4 in
      living cells. Using confocal microscopy and flow cytometric analysis, we showed
      that high levels of CXCR4 are present in the cytoplasm, accompanied by lower
      expression on the cell surface in CXCR4 transfectants, tumor cells, and normal
      peripheral blood lymphocytes. CXCR4 homodimers were detected in tumor cells, both
      on the cell surface membrane and in the cytoplasm using fluorescence resonance
      energy transfer and photobleaching fluorescence resonance energy transfer to
      measure energy transfer between CXCR4-CFP and CXCR4-YFP constructs. Disruption of
      lipid rafts by depletion of cholesterol with methyl-beta-cyclodextrin reduced the
      interaction between CXCR4 molecules and inhibited malignant cell migration to
      CXCL12/SDF-1alpha. A synthetic peptide of TM4 of CXCR4 reduced energy transfer
      between molecules of CXCR4, inhibited CXCL12-induced actin polymerization, and
      blocked chemotaxis of malignant cells. TM4 also inhibited migration of normal
      monocytes toward CXCL12. Reduction of CXCR4 energy transfer by the TM4 peptide
      and methyl-beta-cyclodextrin indicates that interactions between CXCR4s may play
      important roles in cell migration and suggests that cell surface and
      intracellular receptor dimers are appropriate targets for control of tumor cell
      spread. Targeting chemokine receptor oligomerization and signal transduction for
      the treatment of cancer, HIV-1 infections, and other CXCR4 mediated inflammatory
      conditions warrants further investigation.

PMID- 17041092
TI  - Inhibition of cell growth and nuclear factor-kappaB activity in pancreatic cancer
      cell lines by a tylophorine analogue, DCB-3503.
AB  - A tylophorine analogue, DCB-3503, has been shown to have potent activity against
      tumor growth in vitro and in vivo, as well as activity in an autoimmune disease
      model in vivo. This study focuses on investigating the mechanisms responsible for
      antitumor activity of DCB-3503. The concentrations for inhibiting 50%
      growth/colony formation ability are 50/162 and 40/149 nmol/L for PANC-1 and HPAC
      cells, respectively. The growth inhibition effects are associated with DCB-3503
      induced reprogramming of tumor cells. DCB-3503 could interfere with cell cycle
      progression. Several cell cycle regulatory proteins, including cyclin D(1), are
      down-regulated by DCB-3503. Using several different transcription elements
      coupled with a reporter gene, it was found that the nuclear factor-kappaB (NF
      kappaB) signaling pathway is the most sensitive pathway mediator affected by DCB
      3503. The inhibition of NF-kappaB activity is dependent on the down-regulation of
      nuclear phosphorylated p65, a component of the active form of the NF-kappaB
      complex. Such a decrease in nuclear phosphorylated p65 can be reversed by a
      proteosome inhibitor. Furthermore, the activity and protein expression of nuclear
      IkappaB kinase alpha, which is responsible for p65 phosphorylation, is suppressed
      and down-regulated in cells treated with DCB-3503. In summary, DCB-3503 could
      affect cell cycle regulatory proteins and is a potent modulator of NF-kappaB
      function. It is a potentially useful compound in the management of cancers in
      which cyclin D1 overexpression and high NF-kappaB activity play a pivotal role.

PMID- 17041093
TI  - Signaling interactions of rapamycin combined with erlotinib in cervical carcinoma
      xenografts.
AB  - Clinical trials using rapamycin analogues or HER1/epidermal growth factor
      receptor (EGFR) inhibitors show that each class of agent has activity against a
      range of human solid tumors. Because blockade of mitogen-activated protein kinase
      signaling occurs following HER1/EGFR inhibition in some cell types, we tested the
      combination of rapamycin and erlotinib in SiHa, Me180, and CaSki human cervical
      carcinomas xenografts in severe combined immunodeficient mice. In tissue culture,
      all three cell lines showed decreased phosphorylated S6 ribosomal protein and
      decreased phosphorylated extracellular signal-regulated kinase (ERK) following
      treatment with rapamycin and erlotinib, respectively. In SiHa tumors, suppression
      of phosphorylated S6 was induced by either drug alone, whereas phosphorylated ERK
      decreased with erlotinib, and enhancement of these effects was obtained with the
      combination. Continuous treatment of xenografts for 3 weeks led to significant
      tumor growth delay compared with vehicle control for rapamycin as single agent (P
      = 0.003) and greater for the combination (P = 0.04 versus rapamycin). Significant
      antiangiogenic effect was obtained in SiHa xenografts using the drugs together
      (measured by microvascular density and vascular endothelial growth factor plasma
      levels) but not for the single agents. Me180 and CaSki xenografts showed
      significant growth delay with rapamycin but not with erlotinib. Erlotinib
      treatment resulted in decreased phosphorylated ERK, associated with enhanced
      suppression of phosphorylated S6 and improved growth delay in Me180 but not in
      CaSki tumors. These results support the further clinical investigation of
      rapamycin and EGFR inhibitor combinations in anticancer therapy but highlight the
      problem of intertumoral heterogeneity in the prediction of in vivo response.

PMID- 17041094
TI  - Expression of a suicidal gene under control of the human secreted protein acidic
      and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the
      inhibition of tumor cell growth.
AB  - The successful use of transcriptional targeting for cancer therapy depends on the
      activity of a given promoter inside the malignant cell. Because solid human
      tumors evolve as a "cross-talk" between the different cell types within the
      tumor, we hypothesized that targeting the entire tumor mass might have better
      therapeutic effect. Secreted protein acidic and rich in cysteine (SPARC) is a
      matricellular protein overexpressed in different human cancers malignant
      melanomas both in the malignant cells compartment as in the stromal one
      (fibroblasts and endothelial cells). We have shown that expression of the herpes
      simplex virus-thymidine kinase (TK) gene driven by the SPARC promoter in
      combination with ganciclovir inhibited human melanoma cell growth in monolayer as
      well as in multicellular spheroids. This inhibitory effect was observed both in
      homotypic spheroids composed of melanoma cells alone as well as in spheroids made
      of melanoma cells and stromal cells. Expression of the TK gene was also efficient
      to inhibit the in vivo tumor growth of established melanomas when TK was
      expressed either by the malignant cells themselves or by coadministered
      endothelial cells. Our data suggest that the use of therapeutic genes driven by
      SPARC promoter could be a valuable strategy for cancer therapy aiming to target
      all the cellular components of the tumor mass.

PMID- 17041095
TI  - Reverse phase protein array: validation of a novel proteomic technology and
      utility for analysis of primary leukemia specimens and hematopoietic stem cells.
AB  - Proteomics has the potential to provide answers in cancer pathogenesis and to
      direct targeted therapy through the comprehensive analysis of protein expression
      levels and activation status. The realization of this potential requires the
      development of new, rapid, high-throughput technologies for performing protein
      arrays on patient samples, as well as novel analytic techniques to interpret
      them. Herein, we describe the validation and robustness of using reverse phase
      protein arrays (RPPA) for the analysis of primary acute myelogenous leukemia
      samples as well as leukemic and normal stem cells. In this report, we show that
      array printing, detection, amplification, and staining precision are very high,
      reproducible, and that they correlate with traditional Western blotting. Using
      replicates of the same sample on the same and/or separate arrays, or using
      separate protein samples prepared from the same starting sample, the intra- and
      interarray reproducibility was extremely high. No statistically significant
      difference in protein signal intensities could be detected within the array
      setups. The activation status (phosphorylation) was maintained in experiments
      testing delayed processing and preparation from multiple freeze-thawed samples.
      Differences in protein expression could reliably be detected in as few as three
      cell protein equivalents. RPPA prepared from rare populations of normal and
      leukemic stem cells were successfully done and showed differences from bulk
      populations of cells. Examples show how RPPAs are ideally suited for the large
      scale analysis of target identification, validation, and drug discovery. In
      summary, RPPA is a highly reliable, reproducible, high-throughput system that
      allows for the rapid large-scale proteomic analysis of protein expression and
      phosphorylation state in primary acute myelogenous leukemia cells, cell lines,
      and in human stem cells.

PMID- 17041096
TI  - The antitumor effects of sunitinib (formerly SU11248) against a variety of human
      hematologic malignancies: enhancement of growth inhibition via inhibition of
      mammalian target of rapamycin signaling.
AB  - We studied antitumor effects of receptor tyrosine kinase inhibitor sunitinib
      (formerly SU11248) against a variety of hematologic malignancies including the
      following leukemias: eosinophilic (EOL-1), acute myeloid (THP-1, U937, Kasumi-1),
      biphenotypic (MV4-11), acute lymphoblastic (NALL-1, Jurkat, BALL-2, PALL-1, PALL
      2), blast crisis of chronic myeloid (KU812, Kcl-22, K562), and adult T-cell (MT
      1, MT-2, MT-4), as well as non-Hodgkin's lymphoma (KS-1, Dauji, Akata) and
      multiple myeloma (U266). Thymidine uptake studies showed that sunitinib was
      active against EOL-1, MV4-11, and Kasumi-1 cells, which possessed activating
      mutations of the PDGFRalpha, FLT-3, and c-KIT genes, respectively, with IC(50)s
      of <30 nmol/L. In addition, sunitinib inhibited the proliferation of freshly
      isolated leukemia cells from patients possessing mutations in FLT3 gene. Annexin
      V staining showed that sunitinib induced apoptosis of these cells. Sunitinib
      inhibited phosphorylation of FLT3 and PDGFRalpha in conjunction with blockade of
      mammalian target of rapamycin signaling in MV4-11 and EOL-1 cells, respectively.
      Interestingly, rapamycin analogue RAD001 enhanced the ability of sunitinib to
      inhibit the proliferation of leukemia cells and down-regulate levels of mammalian
      target of rapamycin effectors p70 S6 kinase and eukaryotic initiation factor 4E
      binding protein 1 in these cells. Taken together, sunitinib may be useful for
      treatment of individuals with leukemias possessing activation mutation of
      tyrosine kinase, and the combination of sunitinib and RAD001 represents a
      promising novel treatment strategy.

PMID- 17041097
TI  - Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant
      glioma.
AB  - Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA
      alkyltransferase (AGT) has been associated with an enhanced response to
      chloroethylating and methylating agents in patients with malignant glioma. The
      purpose of this study was to compare three distinct yet related indices for
      measuring AGT to determine if these assays could be used interchangeably when AGT
      status is to be used to guide chemotherapeutic decisions. Real-time methylation
      specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal
      beta-actin control, was used to quantitate AGT hypermethylation in 32 glioma
      samples. Data were compared with AGT enzyme activity as well as
      immunohistochemical detection of AGT protein from the same samples.
      Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples
      evaluable by MSP. Low-level AGT, defined as <20% nuclear AGT staining by
      immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%)
      had low levels of AGT activity. Correlation of immunohistochemistry to AGT
      activity was statistically significant (P = 0.014) as was the correlation of
      immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity
      (P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP
      data based on prognostic groups, where good prognosis was represented by an
      immunohistochemistry of <20% and an MSP ratio >12, showed no significant
      relationship (P = 0.214), suggesting that one assay cannot be used
      interchangeably for another. The observed discordance between respective measures
      of AGT based on prognosis supports further standardization of AGT assays designed
      to guide therapeutic practice. The data also suggest that consideration be given
      to the large population of AGT-expressing cells within samples when therapeutic
      strategies based on tumor methylation are used.

PMID- 17041099
TI  - The effect of a novel transition state inhibitor of methylthioadenosine
      phosphorylase on pemetrexed activity.
AB  - Pemetrexed is a new-generation antifolate inhibitor of thymidylate synthase (TS)
      and a weaker inhibitor of glycinamide ribonucleotide transformylase (GARFT)
      required for de novo purine synthesis. Methylthioadenosine phosphorylase (MTAP)
      salvages purines by releasing adenine from methylthioadenosine and is often
      deleted in mesothelioma. The current study addresses the effect of MTAP on
      pemetrexed activity using a highly potent transition state inhibitor of MTAP, MT
      DADMe-Immucillin A (ImmA; K(i) = 86 pmol/L) in the MTAP(+) NCI-H28 and MTAP(-)
      NCI-H2052 mesothelioma cell lines. Based on selective nucleoside protection, TS
      was found to be the primary pemetrexed target in both cell lines with GARFT
      inhibition requiring 20- to 30-fold higher pemetrexed concentrations. ImmA had no
      effect on pemetrexed activity but, when thymidine was added, the pemetrexed
      IC(50) decreased by a factor of approximately 3 in MTAP(+) H28 cells with no
      effect in MTAP(-) H2052 cells. Conversely, the transfection of MTAP into H2052
      cells increased the pemetrexed IC(50) by nearly 3-fold but only in the presence
      of thymidine; this was reversed by ImmA. An MTAP-specific short interfering RNA
      produced a 2-fold decrease in pemetrexed IC(50) in MTAP(+) HeLa cells in the
      presence of thymidine. These data indicate that suppression of constitutive MTAP
      has no effect on pemetrexed activity when the primary target is TS. There is a
      modest salutary effect when the pemetrexed target is GARFT alone.

PMID- 17041098
TI  - The mechanism of methylselenocysteine and docetaxel synergistic activity in
      prostate cancer cells.
AB  - The study was designed to evaluate the combination treatment of
      methylselenocysteine (MSeC) and docetaxel and to delineate the underlying
      mechanism associated with observed in vitro synergy between MSeC and docetaxel in
      prostate cancer cells. Cells were treated with different concentrations and
      schedules (concurrent or sequential) of MSeC and docetaxel alone or in
      combination. Cell growth/death was assessed with sulforhodamine B assay, trypan
      blue assay, and time-lapse video. Loewe synergism/antagonism model was used to
      determine whether the combination effect was additive, synergistic, or
      antagonistic. Apoptosis and caspase-3 activity were evaluated with cell death
      ELISA assay and caspase activity assay, respectively. Synergy between MSeC and
      docetaxel was further assessed in the presence and absence of z-VAD-fmk, a pan
      caspase inhibitor. Effect of MSeC and docetaxel alone or in combination on the
      cellular expression of the antiapoptotic protein survivin was measured with
      Western blot analyses. Pretreatment with MSeC was crucial to enhance docetaxel
      antitumor activity. The enhanced antitumor activity of the sequential combination
      treatment of MSeC and docetaxel (MSeC/docetaxel) was highly synergistic.
      Apoptosis increased after MSeC/docetaxel, compared with each drug alone or
      concurrent treatment. Pretreatment with z-VAD-fmk converted the synergy into
      antagonism, suggesting that the synergy is caspase-dependent apoptosis. The
      survivin level was down-regulated following MSeC/docetaxel treatment when
      compared with each drug alone. In conclusion, pretreatment with MSeC was
      essential to markedly sensitize cells to docetaxel. The synergy between MSeC and
      docetaxel in C2G prostate cancer cells is associated with increased level of
      caspase-dependent apoptosis and decreased level of survivin.

PMID- 17041100
TI  - A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many
      human tumor cell types.
AB  - Urokinase plasminogen activator (uPA) is a tumor-specific protease highly
      expressed in several types of solid tumors and rarely present on normal cells
      under physiologic conditions. Due to its high expression on metastatic tumors,
      several different strategies have been used to target the urokinase system. These
      have mostly led to tumor growth inhibition rather than tumor regression. A
      different approach was adopted by replacing the furin activation site on a
      recombinant anthrax toxin with a urokinase activation site. The resulting toxin,
      PrAgU2/FP59, was highly potent against tumors both in vitro and in vivo. In this
      study, we show that PrAgU2/FP59 is toxic to a wide range of tumor cell lines,
      including non-small cell lung cancer, pancreatic cancer, and basal-like breast
      cancer cell lines. Of the few cell lines found to be resistant to PrAgU2/FP59,
      most became sensitive upon addition of exogenous pro-uPA. PrAgU2/FP59 was much
      less toxic to normal human cells. The potency of PrAgU2/FP59 was dependent on
      anthrax toxin receptor, uPA receptor, and uPA levels but not on total plasminogen
      activator inhibitor-1 levels. In this study, we show that PrAgU2/FP59 is a wide
      range, highly potent, and highly selective toxin that is capable of specifically
      targeting uPA-expressing tumor cells, independently of the tissue of origin of
      these cells. Furthermore, we identify three molecular markers, anthrax toxin
      receptor, uPA, and uPA receptor, which can be used as predictors of tumor cell
      sensitivity to PrAgU2/FP59.

PMID- 17041101
TI  - Synthesis and biological analysis of new curcumin analogues bearing an enhanced
      potential for the medicinal treatment of cancer.
AB  - Curcumin (diferuloylmethane) is a dietary phytochemical with low toxicity that
      exhibits growth-suppressive activity against a variety of cancer cells and
      possesses certain chemopreventive properties. Curcumin has already been the
      subject of several clinical trials for use as a treatment in human cancers.
      Synthetic chemical modifications of curcumin have been studied intensively in an
      attempt to find a molecule with similar but enhanced properties of curcumin. In
      this study, a series of novel curcumin analogues were synthesized and screened
      for anticancer activity. New analogues that exhibit growth-suppressive activity
      30 times that of curcumin and other commonly used anticancer drugs were
      identified. Structurally, the new analogues are symmetrical 1,5
      diarylpentadienone whose aromatic rings possess an alkoxy substitution at each of
      the positions 3 and 5. Analysis of the effects of the analogues on the expression
      of cancer-related genes usually affected by curcumin indicated that some induced
      the down-regulation of beta-catenin, Ki-ras, cyclin D1, c-Myc, and ErbB-2 at as
      low as one eighth the concentration at which curcumin normally has an effect. The
      analogues, however, exhibited neither harmful nor growth-suppressive effects on
      normal hepatocytes where oncogene products are not activated. They also exhibited
      no toxicities in vivo that they may provide effective alternative therapies for
      the prevention and treatment of some human cancers.

PMID- 17041102
TI  - Correction for chromosome-17 is critical for the determination of true Her-2/neu
      gene amplification status in breast cancer.
AB  - PURPOSE: Trastuzumab is the cornerstone for treatment of women with HER2
      overexpressing breast cancer, both in the adjuvant and in the metastatic
      settings. The accurate assessment of HER2 is, therefore, critical to identifying
      patients who may benefit from trastuzumab-based therapy. This project aimed to
      determine the optimal scoring method for fluorescence in situ hybridization
      (FISH) assay. METHODS: FISH assay was done on 893 samples of breast cancer. Three
      scoring methods were evaluated: Her2/CEP17> or =2, Her2>4, or Her2>6. Protein and
      gene expression were evaluated by immunohistochemistry (n = 584) and
      mRNA/assay/nucleic acid sequence-based amplification (NASBA; n = 90). RESULTS:
      Samples were divided into five groups based on FISH results: disomic amplified
      and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of
      cases, mostly positive with Her2>4 scoring, but negative with the others).
      Her2/CEP17> or =2 and Her2>6 scoring methods showed the best association (a) with
      regard to FISH scoring (kappa = 0.906, P < 10(-6)) and (b) between FISH and
      immunohistochemistry (3+ as positive; kappa > 0.650, P < 10(-6)) or NASBA (kappa
      > 0.536, P < 10(-6)). Polysomy had an effect on Her2 copy number (P < 10(-6)),
      but had no effect on protein and mRNA content. Therefore, within the discordant
      subgroup, for which additive Her-2 gene copies are due to high polysomy, protein
      and mRNA levels were similar to those of the nonamplified samples. For this
      subgroup, the best concordance between FISH/immunohistochemistry/NASBA was
      observed with the Her2/CEP17 ratio and Her-2>6 scoring (68% and 58% perfect
      matches, respectively). No perfect matches were observed using the Her2>4 scoring
      method. CONCLUSION: Correction for chromosome-17 is the method of choice for
      clinical practice; Her-2>6, but not Her-2>4, could be used as an alternative.

PMID- 17041103
TI  - Induction of apoptosis by monastrol, an inhibitor of the mitotic kinesin Eg5, is
      independent of the spindle checkpoint.
AB  - Spindle poisons such as paclitaxel are widely used as cancer therapeutics. By
      interfering with microtubule dynamics, paclitaxel induces mitotic arrest and
      apoptosis. Targeting the kinesin Eg5, which is required for the formation of a
      bipolar spindle, is a promising therapeutic alternative to drugs that interfere
      with microtubule dynamics. Recent data suggest that the spindle checkpoint can
      determine the response of tumor cells to microtubule poisons. The relationship
      between checkpoint function and Eg5 inhibition, however, has not yet been fully
      investigated. Here, we used time-lapse video microscopy and biochemical analysis
      to study the effect of spindle checkpoint abrogation on the response of HeLa
      cells to monastrol, a selective Eg5 inhibitor. In HeLa cells, monastrol activated
      the spindle checkpoint, leading to mitotic arrest and apoptosis. Small
      interfering RNA-mediated depletion of the spindle checkpoint proteins BubR1 or
      Mad2 significantly shortened drug-induced arrest, causing premature mitotic exit
      without cell division. Time-lapse microscopy as well as analysis of caspase
      activation shows that these checkpoint-deficient cells initiate apoptosis after
      mitotic exit in response to monastrol. Checkpoint-deficient cells treated with
      paclitaxel, on the other hand, yielded a higher frequency of cells with >4N DNA
      content and a decreased incidence of apoptotic events, particularly in Mad2
      depleted cells. These results indicate that the immediate fate of postmitotic
      cells is influenced by both the nature of the checkpoint defect and the type of
      drug used. Furthermore, these results show that inactivation of the kinesin Eg5
      can induce apoptosis in tumor cells in the absence of critical spindle checkpoint
      components.

PMID- 17041105
TI  - Coronary artery giant aneurysm with fistulas to the left ventricular
      diverticulum.

PMID- 17041106
TI  - Mycotic aneurysm complicating prosthetic valve endocarditis.

PMID- 17041104
TI  - Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy
      of immunotherapy for established lung metastases.
AB  - Expression of the chemokine receptor CXCR4 by tumor cells promotes metastasis,
      possibly by activating prosurvival signals that render cancer cells resistant to
      immune attack. Inhibition of CXCR4 with a peptide antagonist, T22, blocks
      metastatic implantation of CXCR4-transduced B16 (CXCR4-luc-B16) melanoma cells in
      lung, but not the outgrowth of established metastases, raising the question of
      how T22 can best be used in a clinical setting. Herein, whereas the treatment of
      CXCR4-luc-B16 cells in vitro with the CXCR4 ligand CXCL12 did not reduce killing
      induced by cisplatin or cyclophosphamide, CXCL12 markedly reduced Fas-dependent
      killing by gp100-specific (pmel-1) CD8(+) T cells. T22 pretreatment restored
      sensitivity of CXCR4-luc-B16 cells to pmel-1 killing, even in the presence of
      CXCL12. Two immune-augmenting regimens were used in combination with T22 to treat
      experimental lung metastases. First, low-dose cyclophosphamide treatment (100
      mg/kg) on day 5 in combination with T22 (days 4-7) yielded a approximately 70%
      reduction of B16 metastatic tumor burden in the lungs compared with
      cyclophosphamide treatment alone (P < 0.001). Furthermore, whereas anti-CTL
      antigen 4 (CTLA4) monoclonal antibody (mAb; or T22 treatment) alone had little
      effect on established B16 metastases, pretreatment with T22 (in combination with
      anti-CTLA4 mAb) resulted in a 50% reduction in lung tumor burden (P = 0.02).
      Thus, in vitro, CXCR4 antagonism with T22 renders B16 cells susceptible to
      killing by antigen-specific T cells. In vivo, T22 synergizes with
      cyclophosphamide or anti-CTLA4 mAb in the treatment of established lung
      metastases, suggesting a novel strategy for augmenting the efficacy of
      immunotherapy.

PMID- 17041107
TI  - Pathological changes in the coronary arteries in the acute coronary syndromes.

PMID- 17041108
TI  - Live three dimensional echocardiography in evaluation of left ventricular to
      right atrial shunt (Gerbode defect).

PMID- 17041109
TI  - Stent angioplasty in aortic arch interruption.

PMID- 17041110
TI  - Prolapsing left atrial myxoma causing severe pulmonary hypertension: dynamic
      echocardiographic and magnetic resonance imaging.

PMID- 17041111
TI  - Sign of the times.

PMID- 17041112
TI  - Angiographic presentation of sinus of Valsalva aneurysm.

PMID- 17041113
TI  - Endothelialisation of an autologous pericardial valve implanted in the aortic
      position.

PMID- 17041114
TI  - New insight into the tricuspid valve in Ebstein anomaly using three-dimensional
      echocardiography.

PMID- 17041115
TI  - Multislice cardiac computed tomographic images of anomalous origin of the left
      circumflex artery from the right coronary sinus.

PMID- 17041116
TI  - Carbomedics bi-leaflet aortic valve prosthesis: a sticky problem.

PMID- 17041117
TI  - Focal femoral artery narrowing caused by suture mediated closure device.

PMID- 17041118
TI  - Sneddon's syndrome: cardiac involvement detected by magnetic resonance imaging.

PMID- 17041119
TI  - Severe hypothermia showing Osborn waves associated with transient atrial
      fibrillation and ST segment depression.

PMID- 17041120
TI  - Is heart rate variability a valid parameter to predict sudden death in patients
      with Becker's muscular dystrophy?

PMID- 17041121
TI  - Postural sway in patients with syncope and poor orthostatic tolerance.

PMID- 17041122
TI  - Different effects of atenolol and nebivolol on coronary flow reserve.

PMID- 17041123
TI  - Cardiac arrest after occlusion of anomalous origin of left main artery.

PMID- 17041124
TI  - Epidemiology and antibiotic treatment of infective endocarditis: an update.

PMID- 17041125
TI  - Childhood risk factors for adult cardiovascular disease and primary prevention in
      childhood.

PMID- 17041126
TI  - Treating patients with ventricular ectopic beats.

PMID- 17041127
TI  - Value of the sagittal abdominal diameter in coronary heart disease risk
      assessment: cohort study in a large, multiethnic population.
AB  - Whether visceral obesity predicts coronary heart disease (CHD) risk above and
      beyond overall fatness remains unsettled. Moreover, whether the association
      between visceral obesity and CHD risk differs by sex, age, race, and overall
      fatness is poorly understood. The authors conducted a cohort study among 101,765
      adult members of Kaiser Permanente of Northern California who underwent
      multiphasic health checkups between 1965 and 1970. After a median of 12 years and
      adjustment for age, race, body mass index (BMI), educational level, smoking,
      alcohol consumption, and hormone replacement therapy (in women), the upper
      quartile of standing sagittal abdominal diameter, relative to the lowest
      quartile, was associated with a 1.42-fold increased hazard of CHD in men (95%
      confidence interval: 1.30, 1.55) and a 1.44-fold increased hazard of CHD in women
      (95% confidence interval: 1.30, 1.59). Further adjustment for metabolic mediators
      attenuated the association minimally. Standing sagittal abdominal diameter was a
      consistent predictor of CHD across racial groups but was more strongly associated
      with CHD in the younger age group. Joint consideration of BMI/standing sagittal
      abdominal diameter categories better discriminated risk of CHD compared with use
      of BMI alone. In conclusion, standing sagittal abdominal diameter was a strong
      predictor of CHD independently of BMI and added incremental CHD risk prediction
      at each level of BMI.

PMID- 17041128
TI  - Inaccessible novel questionnaires in published medical research: hidden methods,
      hidden costs.
AB  - Although critical analysis of survey research is limited when reviewers and
      readers cannot view a study's questionnaire, access to novel questionnaires used
      in published research has not been systematically examined. The authors
      identified publications reporting the results of novel questionnaires in three
      medical journals (JAMA, The New England Journal of Medicine, and The Lancet) in
      January 2000-May 2003 and searched portable document format (PDF) versions of the
      studies for the complete questionnaire or a Uniform Resource Locator (URL)
      providing access to the questionnaire. When the questionnaire was not provided in
      the publication or a published URL, the authors requested it from the
      corresponding author in writing up to three times over a 6-week period. Of 93
      publications with novel questionnaires, four printed the questionnaire in the
      article and three provided online access. Corresponding authors failed to provide
      questionnaires for 37 of 81 (46%) studies. Novel questionnaires used in published
      research are frequently not available to readers or researchers. Policies that
      improve access to novel questionnaires will allow better assessment of study
      results, reduce duplicated efforts, and improve authorship attribution for
      questionnaire design.

PMID- 17041129
TI  - Height and body mass index and risk of lymphohematopoietic malignancies in two
      million Norwegian men and women.
AB  - Reports on the association between obesity and lymphohematopoietic malignancies
      (LHMs) have been inconsistent. The present study aimed at exploring this
      association for specific disease lymphohematopoietic entities in a large
      Norwegian cohort. Height and weight were measured in two million Norwegian men
      and women aged 20-74 years during 1963-2001. During follow-up, 24,500 cases of
      LHMs were observed. Relative risks of disease were estimated by Cox proportional
      hazards regression. The risk of LHMs overall increased moderately by increasing
      body mass index and height in both sexes. The relative risk of LHMs per five-unit
      increase in body mass index was 1.11 (95% confidence interval (CI): 1.08, 1.14)
      in men and 1.08 (95% CI: 1.05, 1.11) in women. For each 10-cm increase in height,
      the relative risk was 1.19 (95% CI: 1.16, 1.22) in men and 1.16 (95% CI: 1.12,
      1.20) in women. Separate analyses for different lymphohematopoietic malignancies
      did not reveal any group's being particularly strongly associated with body mass
      index. A modest increase in the risk of LHMs combined was observed with
      increasing height. The moderate associations between height and body mass index
      and LHMs found in the present study indicate that the observed increase in
      overweight/obesity plays only a minor role in explaining the increase in the
      incidence of LHMs.

PMID- 17041130
TI  - Re: "confounding of the relation between homocysteine and peripheral arterial
      disease by lead, cadmium, and renal function".

PMID- 17041131
TI  - Spouse resemblance in body mass index: effects on adult obesity prevalence in the
      offspring generation.
AB  - Accruing evidence indicates that mate selection is promoted by similarity in body
      fatness. Assortative mating for obesity may contribute genetically to the obesity
      epidemic by increasing the risk in subsequent generations. To test this
      hypothesis, the authors analyzed measured and validated questionnaire data on
      family members, obtained between 1987 and 2000 from 7,834 obese probands and from
      829 subjects randomly ascertained from the general Swedish population. Spouse
      correlations in body mass index were strongest among couples with the shortest
      duration of cohabitation. Obesity concordance in parents was associated with an
      obesity prevalence of 20.1% in adult offspring compared with 1.4% if parents were
      concordantly nonobese (odds ratio = 18.3, 95% confidence interval: 9.0, 37.4).
      The prevalence was 8.2% if parents were obesity discordant (odds ratio = 6.5, 95%
      confidence interval: 3.2, 13.2). No association was found between rearing
      parents' and nonbiologic offspring's body mass index. These results agree with
      the hypothesis that assortative mating for obesity confers a higher risk of
      obesity in the offspring generation and thus contributes to the obesity epidemic.
      Parental obesity concordance is a strong, easily identifiable genetic risk factor
      that should be considered in the complex network of risk factors for obesity in
      designing primary prevention programs.

PMID- 17041132
TI  - An internet-based method of selecting control populations for epidemiologic
      studies.
AB  - Identifying control subjects for epidemiologic studies continues to increase in
      difficulty because of changes in telephone technology such as answering services
      and machines, caller identification, and cell phones. An Internet-based method
      for obtaining study subjects that may increase response rates has been developed
      and is described. This method uses information from two websites that, when
      combined, provide accurate and complete lists of names, addresses, and listed
      phone numbers. This method was developed by use of randomly selected streets in a
      suburb of Salt Lake City, Utah, in June 2005.

PMID- 17041133
TI  - Invited commentary: the art of making questionnaires better.
AB  - A paper by Schilling et al. (Am J Epidemiol 2006;164:1141-4) addresses a crucial
      issue for epidemiologists: limited peer access to questionnaires. This limited
      access hampers the ability to evaluate and improve the questions used by
      investigators and, in turn, the quality of some of the self-reported data. The
      authors of this commentary analyzed recent publications in core epidemiology
      journals, finding that self-reported data were used in 64% of articles, but key
      questions were seldom printed in the article (9%), and open access to complete
      questionnaires (16%) was rarely provided. Only 47% of articles even discussed
      validation; of these, only 67% actually validated questions used in the study.
      The authors join Schilling et al. in making recommendations to improve
      questionnaire access and collaboration. A first step, proposed before, involves
      investigators posting their questionnaires on a website concurrently with
      publication of their article. Journal editors should require online access to
      full questionnaires for published articles and inclusion of key questions within
      the article when possible. Funding agencies should take the lead in increasing
      access and collaboration by developing a searchable database.

PMID- 17041134
TI  - Childhood socioeconomic position and cause-specific mortality in early adulthood.
AB  - There is growing evidence that childhood socioeconomic position (SEP) influences
      adult health. The authors' aim was to describe the association between childhood
      SEP measures (parents' education, occupation, and income) and mortality, for both
      genders, and to assess to what extent this association was mediated by adult SEP.
      Registry data for all Norwegians born in 1955-1965 were used. Death records were
      linked to the cohort, and 6,589 persons died during 1990-2001. Cox's regression
      was used to calculate relative rates and the relative index of inequality. Low
      childhood SEP was associated with increased mortality for most causes of death,
      except for breast cancer, where no association was found. For suicide in women,
      low childhood SEP was protective. Adult SEP accounted for the associations for
      total mortality and most causes of death. However, adult SEP accounted for only
      one half of the association of father's educational level with ischemic heart
      disease mortality among men. The increased suicide risk among women with high
      childhood SEP persisted, regardless of adult SEP. In summary, childhood SEP had a
      direct association with early adult cardiovascular mortality in men and with
      suicide in women. For other causes of death, childhood SEP was only indirectly
      associated, mostly through persons' own educational level.

PMID- 17041135
TI  - Associations between findings on cranial magnetic resonance imaging and retinal
      photography in the elderly: the Cardiovascular Health Study.
AB  - Associations between findings on cranial magnetic resonance imaging (MRI) and
      retinal photographs have been described mostly in middle-aged people. In the
      Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal
      photography between 1991 and 1999. Associations were sought between MRI findings
      and four findings of retinal microvascular disease: retinopathy, focal arteriolar
      narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based
      upon semiautomated measurements of arterioles and venules. After controlling for
      age and gender, the authors found associations between MRI findings and the
      smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts
      (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter
      grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio =
      1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter
      grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09).
      Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95%
      confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95%
      confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension
      and diabetes had minimal effect. Evidence of small vessel disease in the retina
      increases the likelihood of finding it in the brain. Associations were less
      prominent in this elderly population than have been described in middle-aged
      people.

PMID- 17041136
TI  - Helicobacter pylori persistence: an overview of interactions between H. pylori
      and host immune defenses.
AB  - Helicobacter pylori is a gram-negative bacterium that persistently colonizes more
      than half of the global human population. In order to successfully colonize the
      human stomach, H. pylori must initially overcome multiple innate host defenses.
      Remarkably, H. pylori can persistently colonize the stomach for decades or an
      entire lifetime despite development of an acquired immune response. This review
      focuses on the immune response to H. pylori and the mechanisms by which H. pylori
      resists immune clearance. Three main sections of the review are devoted to (i)
      analysis of the immune response to H. pylori in humans, (ii) analysis of
      interactions of H. pylori with host immune defenses in animal models, and (iii)
      interactions of H. pylori with immune cells in vitro. The topics addressed in
      this review are important for understanding how H. pylori resists immune
      clearance and also are relevant for understanding the pathogenesis of diseases
      caused by H. pylori (peptic ulcer disease, gastric adenocarcinoma, and gastric
      lymphoma).

PMID- 17041137
TI  - Emerging respiratory viruses: challenges and vaccine strategies.
AB  - The current threat of avian influenza to the human population, the potential for
      the reemergence of severe acute respiratory syndrome (SARS)-associated
      coronavirus, and the identification of multiple novel respiratory viruses
      underline the necessity for the development of therapeutic and preventive
      strategies to combat viral infection. Vaccine development is a key component in
      the prevention of widespread viral infection and in the reduction of morbidity
      and mortality associated with many viral infections. In this review we describe
      the different approaches currently being evaluated in the development of vaccines
      against SARS-associated coronavirus and avian influenza viruses and also
      highlight the many obstacles encountered in the development of these vaccines.
      Lessons learned from current vaccine studies, coupled with our increasing
      knowledge of the host and viral factors involved in viral pathogenesis, will help
      to increase the speed with which efficacious vaccines targeting newly emerging
      viral pathogens can be developed.

PMID- 17041138
TI  - Ventilator-associated pneumonia: diagnosis, treatment, and prevention.
AB  - While critically ill patients experience a life-threatening illness, they
      commonly contract ventilator-associated pneumonia. This nosocomial infection
      increases morbidity and likely mortality as well as the cost of health care. This
      article reviews the literature with regard to diagnosis, treatment, and
      prevention. It provides conclusions that can be implemented in practice as well
      as an algorithm for the bedside clinician and also focuses on the controversies
      with regard to diagnostic tools and approaches, treatment plans, and prevention
      strategies.

PMID- 17041140
TI  - Developmental biology of sporozoite-host interactions in Plasmodium falciparum
      malaria: implications for vaccine design.
AB  - The Plasmodium falciparum sporozoite infects different types of cells in a
      mosquito's salivary glands and human epithelial and Kuppfer cells and
      hepatocytes. These become differentiated later on, transforming themselves into
      the invasive red blood cell form, the merozoite. The ability of sporozoites to
      interact with different types of cells requires a wide variety of mechanisms
      allowing them to survive in both hosts: mobility, receptor-ligand interactions
      with different cellular receptors, and transformation and development into other
      invasive parasite forms, which are vitally important for parasite survival.
      Sporozoite complexity is reflected in the large quantity of proteins that can be
      expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP,
      LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in
      infection and their potential use as vaccines. Our work has been focused on the
      search for the molecular mechanisms of parasite-host cellular receptor-ligand
      interactions by identifying amino acid sequences and the critical binding
      residues from these proteins relevant to parasite invasion. Once such sequences
      have been identified, it will be possible to modify them to induce a strong
      immune response against P. falciparum in the experimental Aotus monkey model.
      This all leads towards developing multistage, multicomponent, subunit-based
      vaccines that will be effective in eradicating or controlling malaria caused by
      P. falciparum.

PMID- 17041139
TI  - Molecular epidemiology of tuberculosis: current insights.
AB  - Molecular epidemiologic studies of tuberculosis (TB) have focused largely on
      utilizing molecular techniques to address short- and long-term epidemiologic
      questions, such as in outbreak investigations and in assessing the global
      dissemination of strains, respectively. This is done primarily by examining the
      extent of genetic diversity of clinical strains of Mycobacterium tuberculosis.
      When molecular methods are used in conjunction with classical epidemiology, their
      utility for TB control has been realized. For instance, molecular epidemiologic
      studies have added much-needed accuracy and precision in describing transmission
      dynamics, and they have facilitated investigation of previously unresolved
      issues, such as estimates of recent-versus-reactive disease and the extent of
      exogenous reinfection. In addition, there is mounting evidence to suggest that
      specific strains of M. tuberculosis belonging to discrete phylogenetic clusters
      (lineages) may differ in virulence, pathogenesis, and epidemiologic
      characteristics, all of which may significantly impact TB control and vaccine
      development strategies. Here, we review the current methods, concepts, and
      applications of molecular approaches used to better understand the epidemiology
      of TB.

PMID- 17041141
TI  - Coinfections acquired from ixodes ticks.
AB  - The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis
      can coexist in Ixodes ticks and cause human coinfections. Although the risk of
      human coinfection differs by geographic location, the true prevalence of
      coinfecting pathogens among Ixodes ticks remains largely unknown for the majority
      of geographic locations. The prevalence of dually infected Ixodes ticks appears
      highest among ticks from regions of North America and Europe where LD is endemic,
      with reported prevalences of < or =28%. In North America and Europe, the majority
      of tick-borne coinfections occur among humans with diagnosed LD. Humans
      coinfected with LD and babesiosis appear to have more intense, prolonged symptoms
      than those with LD alone. Coinfected persons can also manifest diverse, influenza
      like symptoms, and abnormal laboratory test results are frequently observed.
      Coinfecting pathogens might alter the efficiency of transmission, cause
      cooperative or competitive pathogen interactions, and alter disease severity
      among hosts. No prospective studies to assess the immunologic effects of
      coinfection among humans have been conducted, but animal models demonstrate that
      certain coinfections can modulate the immune response. Clinicians should consider
      the likelihood of coinfection when pursuing laboratory testing or selecting
      therapy for patients with tick-borne illness.

PMID- 17041142
TI  - Going wild: lessons from naturally occurring T-lymphotropic lentiviruses.
AB  - Over 40 nonhuman primate (NHP) species harbor species-specific simian
      immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic
      felids and African hyenids demonstrate seroreactivity against feline
      immunodeficiency virus (FIV) antigens. While it has been challenging to study the
      biological implications of nonfatal infections in natural populations,
      epidemiologic and clinical studies performed thus far have only rarely detected
      increased morbidity or impaired fecundity/survival of naturally infected SIV- or
      FIV-seropositive versus -seronegative animals. Cross-species transmissions of
      these agents are rare in nature but have been used to develop experimental
      systems to evaluate mechanisms of pathogenicity and to develop animal models of
      HIV/AIDS. Given that felids and primates are substantially evolutionarily removed
      yet demonstrate the same pattern of apparently nonpathogenic lentiviral
      infections, comparison of the biological behaviors of these viruses can yield
      important implications for host-lentiviral adaptation which are relevant to human
      HIV/AIDS infection. This review therefore evaluates similarities in epidemiology,
      lentiviral genotyping, pathogenicity, host immune responses, and cross-species
      transmission of FIVs and factors associated with the establishment of lentiviral
      infections in new species. This comparison of consistent patterns in lentivirus
      biology will expose new directions for scientific inquiry for understanding the
      basis for virulence versus avirulence.

PMID- 17041145
TI  - The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by
      TLR ligands.
AB  - The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of
      the innate host defense system at surfaces of the body. Besides its direct anti
      microbial activity, the peptide interacts with different cell types. Dendritic
      cells (DCs) play a central role in mucosal host defense. It was the aim of the
      study to determine whether LL-37 modulates the response of DCs to pathogen
      associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll
      like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured
      classical markers of DC maturation and assayed the ability of the DCs to activate
      T cell responses. Co-incubation with LL-37 resulted in suppressed activation of
      DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of
      HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure
      of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce
      less IL-2 and IFN-gamma and decreased their proliferation. The response of memory
      T cells to a recall antigen was also decreased. In conclusion, we demonstrate
      that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR
      ligands. We propose that LL-37 is a regulator of host defense responses at the
      intersection of innate and adaptive immune systems.

PMID- 17041143
TI  - Human pharmacogenomic variations and their implications for antifungal efficacy.
AB  - Pharmacogenomics is defined as the study of the impacts of heritable traits on
      pharmacology and toxicology. Candidate genes with potential pharmacogenomic
      importance include drug transporters involved in absorption and excretion, phase
      I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II
      enzymes (e.g., glucuronosyltransferases) contributing to metabolism, and those
      molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the
      distribution of antifungal compounds. By using the tools of population genetics
      to define interindividual differences in drug absorption, distribution,
      metabolism, and excretion, pharmacogenomic models for genetic variations in
      antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become
      especially important in the treatment of immunocompromised patients or those with
      persistent or refractory mycoses that cannot be explained by elevated MICs and
      where rational dosage optimization of the antifungal agent may be particularly
      critical. Pharmacogenomics has the potential to shift the paradigm of therapy and
      to improve the selection of antifungal compounds and adjustment of dosage based
      upon individual variations in drug absorption, metabolism, and excretion.

PMID- 17041144
TI  - Updated review of blood culture contamination.
AB  - Blood culture contamination represents an ongoing source of frustration for
      clinicians and microbiologists alike. Ambiguous culture results often lead to
      diagnostic uncertainty in clinical management and are associated with increased
      health care costs due to unnecessary treatment and testing. A variety of
      strategies have been investigated and employed to decrease contamination rates.
      In addition, numerous approaches to increase our ability to distinguish between
      clinically significant bacteremia and contamination have been explored. In recent
      years, there has been an increase in the application of computer-based tools to
      support infection control activities as well as provide clinical decision support
      related to the management of infectious diseases. Finally, new approaches for
      estimating bacteremia risk which have the potential to decrease unnecessary blood
      culture utilization have been developed and evaluated. In this review, we provide
      an overview of blood culture contamination and describe the potential utility of
      a variety of approaches to improve both detection and prevention. While it is
      clear that progress is being made, fundamental challenges remain.

PMID- 17041146
TI  - A p67Phox-like regulator is recruited to control hyphal branching in a fungal
      grass mutualistic symbiosis.
AB  - Key requirements for microbes to initiate and establish mutualistic symbiotic
      interactions with plants are evasion of potential host defense responses and
      strict control of microbial growth. Reactive oxygen species (ROS) produced by a
      specific NADPH oxidase isoform, NoxA, regulate hyphal growth in the mutualistic
      interaction between the fungal endophyte Epichloe festucae and its grass host
      Lolium perenne. Unlike mammalian systems, little is known about the fungal NADPH
      oxidase complex and its response to differentiation signals. We identify an E.
      festucae p67(phox)-like regulator, NoxR, dispensable in culture but essential in
      planta for the symbiotic interaction. Plants infected with a noxR deletion mutant
      show severe stunting and premature senescence, whereas hyphae in the meristematic
      tissues show increased branching leading to increased fungal colonization of
      pseudostem and leaf blade tissue. Inhibition of ROS production or overexpression
      of noxR recapitulates the hyperbranching phenotype in culture. NoxR interacts in
      vitro with the small GTP binding protein RacA and requires a functional RacA
      binding site to complement the noxR mutant and restore the wild-type plant
      interaction phenotype. These results show that NoxR is a key regulator of NoxA in
      symbiosis, where it acts together with RacA to spatially regulate ROS production
      and control hyphal branching and patterning.

PMID- 17041147
TI  - A pentatricopeptide repeat protein facilitates the trans-splicing of the maize
      chloroplast rps12 pre-mRNA.
AB  - The pentatricopeptide repeat (PPR) is a degenerate 35-amino acid repeat motif
      that is widely distributed among eukaryotes. Genetic, biochemical, and
      bioinformatic data suggest that many PPR proteins influence specific
      posttranscriptional steps in mitochondrial or chloroplast gene expression and
      that they may typically bind RNA. However, biological functions have been
      determined for only a few PPR proteins, and with few exceptions, substrate RNAs
      are unknown. To gain insight into the functions and substrates of the PPR protein
      family, we characterized the maize (Zea mays) nuclear gene ppr4, which encodes a
      chloroplast-targeted protein harboring both a PPR tract and an RNA recognition
      motif. Microarray analysis of RNA that coimmunoprecipitates with PPR4 showed that
      PPR4 is associated in vivo with the first intron of the plastid rps12 pre-mRNA, a
      group II intron that is transcribed in segments and spliced in trans. ppr4
      mutants were recovered through a reverse-genetic screen and shown to be defective
      for rps12 trans-splicing. The observations that PPR4 is associated in vivo with
      rps12-intron 1 and that it is also required for its splicing demonstrate that
      PPR4 is an rps12 trans-splicing factor. These findings add trans-splicing to the
      list of RNA-related functions associated with PPR proteins and suggest that
      plastid group II trans-splicing is performed by different machineries in vascular
      plants and algae.

PMID- 17041148
TI  - A rice Tc1/mariner-like element transposes in yeast.
AB  - The Tc1/mariner transposable element superfamily is widely distributed in animal
      and plant genomes. However, no active plant element has been previously
      identified. Nearly identical copies of a rice (Oryza sativa) Tc1/mariner element
      called Osmar5 in the genome suggested potential activity. Previous studies
      revealed that Osmar5 encoded a protein that bound specifically to its own ends.
      In this report, we show that Osmar5 is an active transposable element by
      demonstrating that expression of its coding sequence in yeast promotes the
      excision of a nonautonomous Osmar5 element located in a reporter construct.
      Element excision produces transposon footprints, whereas element reinsertion
      occurs at TA dinucleotides that were either tightly linked or unlinked to the
      excision site. Several site-directed mutations in the transposase abolished
      activity, whereas mutations in the transposase binding site prevented
      transposition of the nonautonomous element from the reporter construct. This
      report of an active plant Tc1/mariner in yeast will provide a foundation for
      future comparative analyses of animal and plant elements in addition to making a
      new wide host range transposable element available for plant gene tagging.

PMID- 17041149
TI  - Retention of a bean phaseolin/maize gamma-Zein fusion in the endoplasmic
      reticulum depends on disulfide bond formation.
AB  - Most seed storage proteins of the prolamin class accumulate in the endoplasmic
      reticulum (ER) as large insoluble polymers termed protein bodies (PBs), through
      mechanisms that are still poorly understood. We previously showed that a fusion
      between the Phaseolus vulgaris vacuolar storage protein phaseolin and the N
      terminal half of the Zea mays prolamin gamma-zein forms ER-located PBs. Zeolin
      has 6 Cys residues and, like gamma-zein with 15 residues, is insoluble unless
      reduced. The contribution of disulfide bonds to zeolin destiny was determined by
      studying in vivo the effects of 2-mercaptoethanol (2-ME) and by zeolin
      mutagenesis. We show that in tobacco (Nicotiana tabacum) protoplasts, 2-ME
      enhances interactions of newly synthesized proteins with the ER chaperone BiP and
      inhibits the secretory traffic of soluble proteins with or without disulfide
      bonds. In spite of this general inhibition, 2-ME enhances the solubility of
      zeolin and relieves its retention in the ER, resulting in increased zeolin
      traffic. Consistently, mutated zeolin unable to form disulfide bonds is soluble
      and efficiently enters the secretory traffic without 2-ME treatment. We conclude
      that disulfide bonds that lead to insolubilization are a determinant for PB
      mediated protein accumulation in the ER.

PMID- 17041151
TI  - Comparative genome analysis of the neurexin gene family in Danio rerio: insights
      into their functions and evolution.
AB  - Neurexins constitute a family of proteins originally identified as synaptic
      transmembrane receptors for a spider venom toxin. In mammals, the 3 known
      Neurexin genes present 2 alternative promoters that drive the synthesis of a long
      (alpha) and a short (beta) form and contain different sites of alternative
      splicing (AS) that can give rise to thousands of different transcripts. To date,
      very little is known about the significance of this variability, except for the
      modulation of binding to some of the Neurexin ligands. Although orthologs of
      Neurexins have been isolated in invertebrates, these genes have been studied
      mostly in mammals. With the aim of investigating their functions in lower
      vertebrates, we chose Danio rerio as a model because of its increasing importance
      in comparative biology. We have isolated 6 zebrafish homologous genes, which are
      highly conserved at the structural level and display a similar regulation of AS,
      despite about 450 Myr separating the human and zebrafish species. Our data
      indicate a strong selective pressure at the exonic level and on the intronic
      borders, in particular on the regulative intronic sequences that flank the exons
      subject to AS. Such a selective pressure could help conserve the regulation and
      consequently the function of these genes along the vertebrates evolutive tree. AS
      analysis during development shows that all genes are expressed and finely
      regulated since the earliest stages of development, but mark an increase after
      the 24-h stage that corresponds to the beginning of synaptogenesis. Moreover, we
      found that specific isoforms of a zebrafish Neurexin gene (nrxn1a) are expressed
      in the adult testis and in the earliest stages of development, before the
      beginning of zygotic transcription, indicating a potential delivery of paternal
      RNA to the embryo. Our analysis suggests the existence of possible new functions
      for Neurexins, serving as the basis for novel approaches to the functional
      studies of this complex neuronal protein family and more in general to the
      understanding of the AS mechanism in low vertebrates.

PMID- 17041150
TI  - Abiotic stress generates ROS that signal expression of anionic glutamate
      dehydrogenases to form glutamate for proline synthesis in tobacco and grapevine.
AB  - Glutamate dehydrogenase (GDH) may be a stress-responsive enzyme, as GDH exhibits
      considerable thermal stability, and de novo synthesis of the alpha-GDH subunit is
      induced by exogenous ammonium and senescence. NaCl treatment induces reactive
      oxygen species (ROS), intracellular ammonia, expression of tobacco (Nicotiana
      tabacum cv Xanthi) gdh-NAD;A1 encoding the alpha-subunit of GDH, increase in
      immunoreactive alpha-polypeptide, assembly of the anionic isoenzymes, and in
      vitro GDH aminating activity in tissues from hypergeous plant organs. In vivo
      aminating GDH activity was confirmed by gas chromatorgraphy-mass spectrometry
      monitoring of (15)N-Glu, (15)N-Gln, and (15)N-Pro in the presence of methionine
      sulfoximine and amino oxyacetic acid, inhibitors of Gln synthetase and
      transaminases, respectively. Along with upregulation of alpha-GDH by NaCl,
      isocitrate dehydrogenase genes, which provide 2-oxoglutarate, are also induced.
      Treatment with menadione also elicits a severalfold increase in ROS and
      immunoreactive alpha-polypeptide and GDH activity. This suggests that ROS
      participate in the signaling pathway for GDH expression and protease activation,
      which contribute to intracellular hyperammonia. Ammonium ions also mimic the
      effects of salinity in induction of gdh-NAD;A1 expression. These results,
      confirmed in tobacco and grape (Vitis vinifera cv Sultanina) tissues, support the
      hypothesis that the salinity-generated ROS signal induces alpha-GDH subunit
      expression, and the anionic iso-GDHs assimilate ammonia, acting as antistress
      enzymes in ammonia detoxification and production of Glu for Pro synthesis.

PMID- 17041152
TI  - Maximum likelihood estimation of ancestral codon usage bias parameters in
      Drosophila.
AB  - We present a likelihood method for estimating codon usage bias parameters along
      the lineages of a phylogeny. The method is an extension of the classical codon
      based models used for estimating dN/dS ratios along the lineages of a phylogeny.
      However, we add one extra parameter for each lineage: the selection coefficient
      for optimal codon usage (S), allowing joint maximum likelihood estimation of S
      and the dN/dS ratio. We apply the method to previously published data from
      Drosophila melanogaster, Drosophila simulans, and Drosophila yakuba and show, in
      accordance with previous results, that the D. melanogaster lineage has
      experienced a reduction in the selection for optimal codon usage. However, the D.
      melanogaster lineage has also experienced a change in the biological mutation
      rates relative to D. simulans, in particular, a relative reduction in the
      mutation rate from A to G and an increase in the mutation rate from C to T.
      However, neither a reduction in the strength of selection nor a change in the
      mutational pattern can alone explain all of the data observed in the D.
      melanogaster lineage. For example, we also confirm previous results showing that
      the Notch locus has experienced positive selection for previously classified
      unpreferred mutations.

PMID- 17041153
TI  - Molecular architecture of the DNA-binding region and its relationship to
      classification of basic helix-loop-helix proteins.
AB  - Multivariate statistical analyses are used to explore the molecular architecture
      of the DNA-binding and dimerization regions of basic helix-loop-helix (bHLH)
      proteins. Alphabetic amino acid data are transformed to biologically meaningful
      quantitative values using a set of 5 multivariate "indices." These multivariate
      indices summarize variation in a large suite of amino acid physiochemical
      attributes and reflect variability in polarity-accessibility-hydrophobicity,
      propensity for secondary structure, molecular size, codon composition, and
      electrostatic charge. Using these index score data, discriminant analyses
      describe the multidimensional aspects of physiochemical variation and clarify the
      structural basis of the prevailing evolutionary classification of bHLH proteins.
      A small number of amino acids from both the binding dimerization domains, when
      considered simultaneously, accurately distinguish the 5 known DNA-binding groups.
      The relevant sites often have well-documented structural and functional
      characteristics.

PMID- 17041154
TI  - Genetic manipulation of Prochlorococcus strain MIT9313: green fluorescent protein
      expression from an RSF1010 plasmid and Tn5 transposition.
AB  - Prochlorococcus is the smallest oxygenic phototroph yet described. It numerically
      dominates the phytoplankton community in the mid-latitude oceanic gyres, where it
      has an important role in the global carbon cycle. The complete genomes of several
      Prochlorococcus strains have been sequenced, revealing that nearly half of the
      genes in each genome are of unknown function. Genetic methods, such as reporter
      gene assays and tagged mutagenesis, are critical to unveiling the functions of
      these genes. Here, we describe conditions for the transfer of plasmid DNA into
      Prochlorococcus strain MIT9313 by interspecific conjugation with Escherichia
      coli. Following conjugation, E. coli bacteria were removed from the
      Prochlorococcus cultures by infection with E. coli phage T7. We applied these
      methods to show that an RSF1010-derived plasmid will replicate in Prochlorococcus
      strain MIT9313. When this plasmid was modified to contain green fluorescent
      protein, we detected its expression in Prochlorococcus by Western blotting and
      cellular fluorescence. Further, we applied these conjugation methods to show that
      a mini-Tn5 transposon will transpose in vivo in Prochlorococcus. These genetic
      advances provide a basis for future genetic studies with Prochlorococcus, a
      microbe of ecological importance in the world's oceans.

PMID- 17041155
TI  - Virus-specific responses of Heterosigma akashiwo to infection.
AB  - We used flow cytometry to examine the process of cell death in the bloom-forming
      alga Heterosigma akashiwo during infection by a double-stranded DNA virus (OIs1)
      and a single-stranded RNA virus (H. akashiwo RNA virus [HaRNAV]). These viruses
      were isolated from the same geographic area and infect the same strain of H.
      akashiwo. By use of the live/dead stains fluorescein diacetate and SYTOX green as
      indicators of cellular physiology, cells infected with OIs1 showed signs of
      infection earlier than HaRNAV-infected cultures (6 to 17 h versus 23 to 29 h).
      Intracellular esterase activity was lost prior to increased membrane permeability
      during infection with OIs1, while the opposite was seen with HaRNAV-infected
      cultures. In addition, OIs1-infected cells accumulated in the cultures while
      HaRNAV-infected cells rapidly disintegrated. Progeny OIs1 viruses consisted of
      large and small morphotypes with estimated latent periods of 11 and 17 h,
      respectively, and about 1,100 and 16,000 viruses produced per cell, respectively.
      In contrast, HaRNAV produced about 21,000 viruses per cell and had a latent
      period of 29 h. This study reveals that the characteristics of viral infection in
      algae are virus dependent and therefore are variable among viruses infecting the
      same species. This is an important consideration for ecosystem modeling
      exercises; calculations based on in situ measurements of algal physiology must be
      sensitive to the diverse responses of algae to viral infection.

PMID- 17041156
TI  - Bestowing inducibility on the cloned methanol dehydrogenase promoter (PmxaF) of
      Methylobacterium extorquens by applying regulatory elements of Pseudomonas putida
      F1.
AB  - PmxaF is a strong methanol-inducible promoter in Methylobacterium extorquens.
      When this promoter is cloned in expression vectors and used to drive heterologous
      gene expression, methanol inducibility is either greatly reduced or entirely
      lost. In order to bestow inducibility upon the cloned PmxaF promoter in
      expression vectors, we adopted combinational methods (regulatory elements of the
      Pseudomonas putida F1 cym and cmt operons and Tn7 transposon system) to control
      reporter gene expression at the transcriptional level in M. extorquens. An
      operator fragment (26 nucleotides) of the cmt operon was inserted downstream of
      the cloned PmxaF promoter in the broad-host-range expression vector (pCHOI3). The
      repressor gene (cymR) located upstream of the cym operon in P. putida F1 was
      amplified by PCR. To avoid cellular toxicity for M. extorquens caused by the
      overexpression of CymR, single and/or double copies of cymR were integrated into
      the chromosome of M. extorquens using the mini-Tn7 transposon system. Cultures
      containing the chromosomally integrated cymR gene were subsequently transformed
      with pCHOI3 containing modified PmxaF (i.e., PmxaF plus operator). In this
      construct, inducibility is afforded by cumate (p-isopropylbenzoate). In this
      report, we describe the inducible and tightly regulated expression of
      heterologous genes (bgl [for beta-galactosidase], est [for esterase], and gfp
      [for green fluorescent protein]) in M. extorquens. This is the first documented
      example of an inducible/regulated heterologous gene expression system in M.
      extorquens.

PMID- 17041157
TI  - Study of biochemical pathways and enzymes involved in pyrene degradation by
      Mycobacterium sp. strain KMS.
AB  - Pyrene degradation is known in bacteria. In this study, Mycobacterium sp. strain
      KMS was used to study the metabolites produced during, and enzymes involved in,
      pyrene degradation. Several key metabolites, including pyrene-4,5-dione, cis-4,5
      pyrene-dihydrodiol, phenanthrene-4,5-dicarboxylic acid, and 4-phenanthroic acid,
      were identified during pyrene degradation. Pyrene-4,5-dione, which accumulates as
      an end product in some gram-negative bacterial cultures, was further utilized and
      degraded by Mycobacterium sp. strain KMS. Enzymes involved in pyrene degradation
      by Mycobacterium sp. strain KMS were studied, using 2-D gel electrophoresis. The
      first protein in the catabolic pathway, aromatic-ring-hydroxylating dioxygenase,
      which oxidizes pyrene to cis-4,5-pyrene-dihydrodiol, was induced with the
      addition of pyrene and pyrene-4,5-dione to the cultures. The subcomponents of
      dioxygenase, including the alpha and beta subunits, 4Fe-4S ferredoxin, and the
      Rieske (2Fe-2S) region, were all induced. Other proteins responsible for further
      pyrene degradation, such as dihydrodiol dehydrogenase, oxidoreductase, and
      epoxide hydrolase, were also found to be significantly induced by the presence of
      pyrene and pyrene-4,5-dione. Several nonpathway-related proteins, including
      sterol-binding protein and cytochrome P450, were induced. A pyrene degradation
      pathway for Mycobacterium sp. strain KMS was proposed and confirmed by proteomic
      study by identifying almost all the enzymes required during the initial steps of
      pyrene degradation.

PMID- 17041158
TI  - Sec-mediated transport of posttranslationally dehydrated peptides in Lactococcus
      lactis.
AB  - Nisin is a lanthionine-containing antimicrobial peptide produced by Lactococcus
      lactis. Its (methyl)lanthionines are introduced by two posttranslational
      enzymatic steps involving the dehydratase NisB, which dehydrates serine and
      threonine residues, and the cyclase NisC, which couples these dehydrated residues
      to cysteines, yielding thioether-bridged amino acids called lanthionines. The
      prenisin is subsequently exported by the ABC transporter NisT and extracellularly
      processed by the peptidase NisP. L. lactis expressing the nisBTC genes can modify
      and secrete a wide range of nonlantibiotic peptides. Here we demonstrate that in
      the absence of NisT and NisC, the Sec pathway of L. lactis can be exploited for
      the secretion of dehydrated variants of therapeutic peptides. Furthermore,
      posttranslational modifications by NisB and NisC still occur even when the nisin
      leader is preceded by a Sec signal peptide or a Tat signal peptide 27 or 44 amino
      acids long, respectively. However, transport of fully modified prenisin via the
      Sec pathway is impaired. The extent of NisB-mediated dehydration could be
      improved by raising the intracellular concentration NisB or by modulating the
      export efficiency through altering the signal sequence. These data demonstrate
      that besides the traditional lantibiotic transporter NisT, the Sec pathway with
      an established broad substrate range can be utilized for the improved export of
      lantibiotic enzyme-modified (poly)peptides.

PMID- 17041159
TI  - Different levels of transcriptional regulation due to trophic constraints in the
      reduced genome of Buchnera aphidicola APS.
AB  - Symbiotic associations involving intracellular microorganisms and animals are
      widespread, especially for species feeding on poor or unbalanced diets. Buchnera
      aphidicola, the obligate intracellular bacterium associated with most aphid
      species, provides its hosts with essential amino acids (EAAs), nutrients in short
      supply in the plant phloem sap. The Buchnera genome has undergone severe
      reductions during intracellular evolution. Genes for EAA biosynthesis are
      conserved, but most of the transcriptional regulatory elements are lost. This
      work addresses two main questions: is transcription in Buchnera (i) regulated and
      (ii) scaled to aphid EAA demand? Two microarray experiments were designed for
      profiling the gene expression in Buchnera. The first one was characterized by a
      specific depletion of tyrosine and phenylalanine in the aphid diet, and the
      second experiment combined a global diminution of EAAs in the aphid diet with a
      sucrose concentration increase to manipulate the aphid growth rate. Aphid
      biological performance and budget analysis (the balance between EAAs provided by
      the diet and those synthesized by Buchnera) were performed to quantify the
      nutritional demand from the aphids toward their symbiotic bacteria. Despite the
      absence of known regulatory elements, a significant transcriptional regulation
      was observed at different levels of organization in the Buchnera genome: between
      genes, within putative transcription units, and within specific metabolic
      pathways. However, unambiguous evidence for transcriptional changes underpinning
      the scaling of EAA biosynthesis to aphid demand was not obtained. The phenotypic
      relevance of the transcriptional response from the reduced genome of Buchnera is
      addressed.

PMID- 17041160
TI  - Antimicrobial use and resistance in swine waste treatment systems.
AB  - Chlortetracycline and the macrolide tylosin were identified as commonly used
      antimicrobials for growth promotion and prophylaxis in swine production.
      Resistance to these antimicrobials was measured throughout the waste treatment
      processes at five swine farms by culture-based and molecular methods.
      Conventional farm samples had the highest levels of resistance with both culture
      based and molecular methods and had similar levels of resistance despite
      differences in antimicrobial usage. The levels of resistance in organic farm
      samples, where no antimicrobials were used, were very low by a culture-based
      method targeting fecal streptococci. However, when the same samples were analyzed
      with a molecular method detecting methylation of a specific nucleotide in the 23S
      rRNA that results in resistance to macrolides, lincosamides, and streptogramin B
      (MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was
      observed, suggesting that the fecal streptococci were not an appropriate target
      group to evaluate resistance in the overall microbial community and that
      background levels of MLSB resistance may be substantial. All of the feed samples
      tested, including those from the organic farm, contained tetracycline resistance
      genes. Generally, the same tetracycline resistance genes and frequency of
      detection were found in the manure and lagoon samples for each commercial farm.
      The levels of tetracycline and MLSB resistance remained high throughout the waste
      treatment systems, suggesting that the potential impact of land application of
      treated wastes and waste treatment by-products on environmental levels of
      resistance should be investigated further.

PMID- 17041162
TI  - Identification of human and animal adenoviruses and polyomaviruses for
      determination of sources of fecal contamination in the environment.
AB  - The Adenoviridae and Polyomaviridae families comprise a wide diversity of viruses
      which may be excreted for long periods in feces or urine. In this study, a
      preliminary analysis of the prevalence in the environment and the potential
      usefulness as source-tracking tools of human and animal adenoviruses and
      polyomaviruses has been developed. Molecular assays based on PCR specifically
      targeting human adenoviruses (HAdV), porcine adenoviruses (PAdV), bovine
      adenoviruses (BAdV), and bovine polyomaviruses (BPyV) were applied to
      environmental samples including urban sewage, slaughterhouse, and river water
      samples. PAdV and BPyV were detected in a very high percentage of samples
      potentially affected by either porcine or bovine fecal contamination,
      respectively. However, BAdV were detected in only one sample, showing a lower
      prevalence than BPyV in the wastewater samples analyzed. The 22 slaughterhouse
      samples with fecal contamination of animal origin showed negative results for the
      presence of HAdV. The river water samples analyzed were positive for the presence
      of both human and animal adenoviruses and polyomaviruses, indicating the
      existence of diverse sources of contamination. The identities of the viruses
      detected were confirmed by analyses of the amplified sequences. All BPyV isolates
      showed a 97% similarity in nucleotide sequences. This is the first time that
      PAdV5, BAdV6, and BPyV have been reported to occur in environmental samples.
      Human and porcine adenoviruses and human and bovine polyomaviruses are proposed
      as tools for evaluating the presence of viral contamination and for tracking the
      origin of fecal/urine contamination in environmental samples.

PMID- 17041163
TI  - Comparative effects of osmotic, sodium nitrite-induced, and pH-induced stress on
      growth and survival of Clostridium perfringens type A isolates carrying
      chromosomal or plasmid-borne enterotoxin genes.
AB  - About 1 to 2% of Clostridium perfringens isolates carry the enterotoxin gene
      (cpe) necessary for causing C. perfringens type A food poisoning. While the cpe
      gene can be either chromosomal or plasmid borne, food poisoning isolates usually
      carry a chromosomal cpe gene. Previous studies have linked this association
      between chromosomal cpe isolates (i.e., C-cpe isolates) and food poisoning, at
      least in part, to both the spores and vegetative cells of C-cpe isolates being
      particularly resistant to high and low temperatures. The current study now
      reveals that the resistance phenotype of C-cpe isolates extends beyond
      temperature resistance to also include, for both vegetative cells and spores,
      enhanced resistance to osmotic stress (from NaCl) and nitrites. However, by
      omitting one outlier isolate, no significant differences in pH sensitivity were
      detected between the spores or vegetative cells of C-cpe isolates versus isolates
      carrying a plasmid-borne cpe gene. These results indicate that both vegetative
      cells and spores of C-cpe isolates are unusually resistant to several food
      preservation approaches in addition to temperature extremes. The broad-spectrum
      nature of the C-cpe resistance phenotype suggests these bacteria may employ
      multiple mechanisms to persist and grow in foods prior to their transmission to
      humans.

PMID- 17041164
TI  - Inactivation of poliovirus 1 and F-specific RNA phages and degradation of their
      genomes by UV irradiation at 254 nanometers.
AB  - Several models (animal caliciviruses, poliovirus 1 [PV1], and F-specific RNA
      bacteriophages) are usually used to predict inactivation of nonculturable
      viruses. For the same UV fluence, viral inactivation observed in the literature
      varies from 0 to 5 logs according to the models and the methods (infectivity
      versus molecular biology). The lack of knowledge concerning the mechanisms of
      inactivation due to UV prevents us from selecting the best model. In this
      context, determining if viral genome degradation may explain the loss of
      infectivity under UV radiation becomes essential. Thus, four virus models (PV1
      and three F-specific RNA phages: MS2, GA, and Qbeta) were exposed to UV radiation
      from 0 to 150 mJ.cm-2. PV1 is the least-resistant virus, while MS2 and GA phages
      are the most resistant, with phage Qbeta having an intermediate sensitivity;
      respectively, 6-log, 2.3-log, 2.5-log, and 4-log decreases for 50 mJ.cm-2. In
      parallel, analysis of RNA degradation demonstrated that this phenomenon depends
      on the fragment size for PV1 as well as for MS2. Long fragments (above 2,000
      bases) for PV1 and MS2 fell rapidly to the background level (>1.3-log decrease)
      for 20 mJ.cm-2 and 60 mJ.cm-2, respectively. Nevertheless, the size of the viral
      RNA is not the only factor affecting UV-induced RNA degradation, since viral RNA
      was more rapidly degraded in PV1 than in the MS2 phage with a similar size.
      Finally, extrapolation of inactivation and UV-induced RNA degradation kinetics
      highlights that genome degradation could fully explain UV-induced viral
      inactivation.

PMID- 17041165
TI  - Rationale for use of Tdap booster vaccines for adolescent immunization: overview
      of efficacy, safety, and clinical use.
AB  - Pertussis is one of the only vaccine-preventable diseases with increasing
      incidence in the United States. The incidence of pertussis infection in
      adolescents is a growing concern; it can be a severe disease that may lead to
      significant morbidity and mortality when transmitted to susceptible populations
      (eg, infants). Experts have conceded that booster vaccination of adolescents may
      considerably decrease the incidence of pertussis infections in previously
      immunized, partially immunized, and nonimmunized populations. Studies in 2
      tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccines licensed by
      the Food and Drug Administration (FDA) have shown efficacy against pertussis
      disease and have demonstrated a safety profile comparable to tetanus and
      diphtheria vaccine (Td) in adolescents. Immunization schedules now include use of
      Tdap vaccines for preadolescent and adolescent populations to counter the
      increase in pertussis outbreaks. Challenges for clinicians include prompt
      recognition of pertussis symptoms, proper diagnosis using appropriate tools, and
      timely reporting of pertussis infections to surveillance bodies. Additional
      studies are needed to monitor trends of pertussis incidence after implementing
      the new vaccination schedule for adolescents.

PMID- 17041166
TI  - Catheterization of the bladder in infants and children.
AB  - Catheterization of the urinary bladder is a common procedure that can be
      emotionally and physically traumatic for the child and family. The purpose of
      this review is to familiarize readers with the procedure and techniques that will
      minimize the physical and emotional discomfort, and complications.

PMID- 17041161
TI  - Community structure analyses are more sensitive to differences in soil bacterial
      communities than anonymous diversity indices.
AB  - Changes in the diversity and structure of soil microbial communities may offer a
      key to understanding the impact of environmental factors on soil quality in
      agriculturally managed systems. Twenty-five years of biodynamic, bio-organic, or
      conventional management in the DOK long-term experiment in Switzerland
      significantly altered soil bacterial community structures, as assessed by
      terminal restriction fragment length polymorphism (T-RFLP) analysis. To evaluate
      these results, the relation between bacterial diversity and bacterial community
      structures and their discrimination potential were investigated by sequence and T
      RFLP analyses of 1,904 bacterial 16S rRNA gene clones derived from the DOK soils.
      Standard anonymous diversity indices such as Shannon, Chao1, and ACE or
      rarefaction analysis did not allow detection of management-dependent influences
      on the soil bacterial community. Bacterial community structures determined by
      sequence and T-RFLP analyses of the three gene libraries substantiated changes
      previously observed by soil bacterial community level T-RFLP profiling. This
      supported the value of high-throughput monitoring tools such as T-RFLP analysis
      for assessment of differences in soil microbial communities. The gene library
      approach also allowed identification of potential management-specific indicator
      taxa, which were derived from nine different bacterial phyla. These results
      clearly demonstrate the advantages of community structure analyses over those
      based on anonymous diversity indices when analyzing complex soil microbial
      communities.

PMID- 17041167
TI  - Diagnosis and management of childhood bipolar disorder in the primary care
      setting.
AB  - Early-onset bipolar disorder (BD) is often misdiagnosed and inadequately treated
      because of the varying constellation of symptoms that occur across different
      developmental stages, the variety of disorders with similar presentation, and the
      frequent comorbidities. The etiology of BD is complex, but research confirms the
      major role that genetics and environment play in its development. The
      pediatrician initially identifies most cases, with subsequent referral to mental
      health providers. A complex case involving a child initially diagnosed with
      attention deficit hyperactivity disorder (ADHD) and later found to have comorbid
      childhood BD is considered, illustrating diagnostic considerations and
      appropriate behavioral and psychopharmacological intervention.

PMID- 17041168
TI  - Melatonin treatment in adolescents with delayed sleep phase syndrome.
AB  - This retrospective study describes the effects of long-term treatment with
      melatonin in 33 adolescents (age range, 10-18 years) with delayed sleep phase
      syndrome (DSPS). Patients were treated with oral melatonin, 3 to 5 mg/day for an
      average period of 6 months. During the treatment, sleep onset was advanced and
      sleep duration was longer. Treatment was also associated with a decrease in the
      proportion of patients reporting school difficulties. No adverse effects of
      melatonin were noted. This study indicates that long-term treatment with
      melatonin can be beneficial for adolescents with DSPS in terms of sleep-wake
      schedule and school performance.

PMID- 17041169
TI  - Atomoxetine in the management of children with ADHD: effects on quality of life
      and school functioning.
AB  - The purpose of this study was to examine in a controlled trial the effects of
      atomoxetine on the management of attention deficit-hyperactivity disorder (ADHD)
      symptoms and functional impairments at school and at home. Participants were 153
      children (age 8 to 12 years) diagnosed with attention-deficit hyperactivity
      disorder who were randomized to double-blind treatment with either atomoxetine (n
      = 101) or placebo (n = 52). Findings revealed significant improvements both for
      parent and teacher ratings of behavior for children receiving atomoxetine
      therapy. Children also were reported to evidence a trend toward better response
      to active medication than to placebo for health-related quality of life as rated
      by parents. No significant effects were revealed for the teacher ratings of
      academic productivity. Data were interpreted to provide support for the efficacy
      of atomoxetine on the symptoms associated with ADHD. The effects of atomoxetine
      on other functional outcomes including academic performance and health-related
      outcomes are of interest, albeit less compelling for this particular
      investigation, than for the effects on overt symptom display.

PMID- 17041170
TI  - The attitude of physicians toward cold remedies for upper respiratory infection
      in infants and children: a questionnaire survey.
AB  - Over-the-counter cold remedies are widely used for symptomatic relief of upper
      respiratory tract infections. The safety of these drugs is not well established
      in infants and their efficacy is questionable. Our aim was to study the attitude
      of family physicians and pediatricians toward the use of cold remedies in infants
      and children. A questionnaire was sent to 400 family physicians and 100
      pediatricians randomly selected across Ontario. The overall response rate was
      53.2%. Sixteen percent of family physicians recommended cold remedies for infants
      0 to 6 months of age compared to 4% of the pediatricians (P = 0.01). For infants
      6 to 12 months of age, the difference between pediatricians and family physicians
      persisted (14% and 38% of, respectively; P < 0.001). Despite that cold remedies
      are not proven to be effective and some safety issues are associated with their
      use in the pediatric age group, physicians still recommend them. Continuing
      medical education programs should address the issue.

PMID- 17041171
TI  - A multimedia program helps parents manage childhood aggression.
AB  - Participants were 65 parents of 6- to 18-month-old children presenting for a well
      child checkup between September 2002 and February 2003 to one of two private
      pediatric offices. The intervention was a 30-minute multimedia program, Play
      Nicely, viewed at home, which teaches the basics in childhood aggression
      management. One year after intervention, parents were asked, "Do you feel that
      the CD program was helpful in managing aggressive behavior in your child?" Most
      (65%) parents who watched the program agreed that it helped them manage
      aggression with their own child (strongly agree, 31%; agree, 34%; uncertain, 28%;
      disagree, 7%; and strongly disagree, 0%). An inexpensive, brief, independently
      viewed, multimedia program helps parents manage aggression in their young
      children as long as 1 year after receiving it from their pediatrician. An easily
      implemented intervention may contribute to violence prevention efforts.

PMID- 17041172
TI  - Prenatal office practices regarding infant feeding choices.
AB  - The objective of this study was to determine the obstetric care providers' roles
      in breast-feeding promotion during prenatal care. A questionnaire addressing
      breast-feeding issues was sent to family practitioners (FP), obstetric
      gynecologists (OB/GYN), and nurse midwives (NM) in Iowa, USA. All NM, 97% of FP,
      and 85% of OB/GYN reported asking infant feeding preference-usually only at the
      first prenatal visit. NM (73%) were most likely to provide extensive breast
      feeding counseling. OB/GYN (68%) and FP physicians (90%) reported doing their own
      breast-feeding counseling. Breast examinations targeting future breast-feeding
      problems were done in 82% to 84% of patients. NM practices shared more
      information supportive of breast-feeding. Nearly all providers offered prenatal
      classes, but only 41% of FP offered breast-feeding classes. Free formula samples
      were available in 73% of FP, 54% of OB/GYN, and 36% NM offices. Pamphlets on
      formula feeding and also breast-feeding were readily available. Overall NM (64%)
      reported being strong breast-feeding advocates compared to only 13% of FP and 7%
      of OB/GYN. In conclusion, little promotion of breast-feeding occurs in most
      prenatal practice settings.

PMID- 17041173
TI  - Teaching practice management skills to pediatric residents.
AB  - To satisfy the core competencies required by the Pediatric Residency Review
      Committee, the author describes an educational program for the residents in a
      large pediatric training program. The course provides a year-long overview of
      multiple medical management topics. The sessions cover nonclinical subjects
      usually missed in other educational settings, with particular focus on areas of
      finance, compliance, personnel management, career advancement, and leadership.
      The series is currently in its third year, with a positive response from the
      participants, and demonstrated improvement in resident knowledge of the covered
      areas.

PMID- 17041174
TI  - Infants fed docosahexaenoic acid- and arachidonic acid-supplemented formula have
      decreased incidence of bronchiolitis/bronchitis the first year of life.
AB  - To assess the effect of docosahexaenoic acid and arachidonic acid supplementation
      in infant formula on the incidence of respiratory illnesses, pediatricians
      assigned infants to receive docosahexaenoic acid/arachidonic acid-supplemented
      formula or control formula. Anthropometrics, medical history, and illnesses were
      reported. Among 1342 infants, there was a higher incidence of bronchiolitis in
      control versus docosahexaenoic acid/arachidonic acid-supplemented groups at 5, 7,
      and 9 months (P < .01). Weight, length, and head circumference were similar for
      both groups. Infants fed formula supplemented with 0.32% docosahexaenoic acid and
      0.64% arachidonic acid experienced a lower incidence of bronchiolitis compared
      with infants fed formula supplemented with no docosahexaenoic acid/arachidonic
      acid or lower levels of docosahexaenoic acid/arachidonic acid in the first year
      of life.

PMID- 17041175
TI  - The safety of mineral oil in the treatment of constipation--a lesson from
      prolonged overdose.
AB  - There have been concerns regarding the interference in the absorption of fat
      soluble vitamins in long-term treatment with mineral oil; however, there is no
      clear evidence in the literature to support this claim. We present a case report
      illustrating the effect of prolonged (5 months) large doses of mineral oil on the
      fat-soluble vitamin absorption in a 17-year-old girl.

PMID- 17041176
TI  - Painless bloody nipple discharge in a 16-month-old infant.

PMID- 17041177
TI  - Mollaret's meningitis due to human herpesvirus 6 in an adolescent.
AB  - We report the first pediatric case of Mollaret meningitis in an adolescent female
      with acute lymphoblastic leukemia in remission. This patient had signs and
      symptoms consistent with meningitis, with three episodes over a 3-month period.
      Human herpesvirus 6 (HHV-6) was identified during her last episode from
      polymerase chain reaction assay of a cerebrospinal fluid specimen. She was
      treated successfully with foscarnet, after which HHV-6 was undetectable in her
      cerebrospinal fluid.

PMID- 17041178
TI  - Smelling like dead fish: a case of trimethylaminuria in an adolescent.

PMID- 17041179
TI  - Buttock spots.

PMID- 17041180
TI  - Chronic cough.

PMID- 17041181
TI  - Bullying.

PMID- 17041184
TI  - Peroxisome function regulates growth on glucose in the basidiomycete fungus
      Cryptococcus neoformans.
AB  - The function of the peroxisomes was examined in the pathogenic basidiomycete
      Cryptococcus neoformans. Recent studies reveal the glyoxylate pathway is required
      for virulence of diverse microbial pathogens of plants and animals. One exception
      is C. neoformans, in which isocitrate lyase (encoded by ICL1) was previously
      shown not to be required for virulence, and here this was extended to exclude
      also a role for malate synthase (encoded by MLS1). The role of peroxisomes, in
      which the glyoxylate pathway enzymes are localized in many organisms, was
      examined by mutation of two genes (PEX1 and PEX6) encoding AAA (ATPases
      associated with various cellular activities)-type proteins required for
      peroxisome formation. The pex1 and pex6 deletion mutants were unable to localize
      the fluorescent DsRED-SKL protein to peroxisomal punctate structures, in contrast
      to wild-type cells. pex1 and pex6 single mutants and a pex1 pex6 double mutant
      exhibit identical phenotypes, including abolished growth on fatty acids but no
      growth difference on acetate. Because both icl1 and mls1 mutants are unable to
      grow on acetate as the sole carbon source, these findings demonstrate that the
      glyoxylate pathway can function efficiently outside the peroxisome in C.
      neoformans. The pex1 mutant exhibits wild-type virulence in a murine inhalation
      model and in an insect host, demonstrating that peroxisomes are not required for
      virulence under these conditions. An unusual phenotype of the pex1 and pex6
      mutants was that they grew poorly with glucose as the carbon source, but nearly
      wild type with galactose, which suggested impaired hexokinase function and that
      C. neoformans peroxisomes might function analogously to the glycosomes of the
      trypanosomid parasites. Deletion of the hexokinase HXK2 gene reduced growth in
      the presence of glucose and suppressed the growth defect of the pex1 mutant on
      glucose. The hexokinase 2 protein of C. neoformans contains a predicted
      peroxisome targeting signal (type 2) motif; however, Hxk2 fused to fluorescent
      proteins was not localized to peroxisomes. Thus, we hypothesize that glucose or
      glycolytic metabolites are utilized in the peroxisome by an as yet unidentified
      enzyme or regulate a pathway required by the fungus in the absence of
      peroxisomes.

PMID- 17041185
TI  - Parallels in fungal pathogenesis on plant and animal hosts.

PMID- 17041186
TI  - Identification of translational regulation target genes during filamentous growth
      in Saccharomyces cerevisiae: regulatory role of Caf20 and Dhh1.
AB  - The dimorphic transition of yeast to the hyphal form is regulated by the mitogen
      activated protein kinase and cyclic AMP-dependent protein kinase A pathways in
      Saccharomyces cerevisiae. Signaling pathway-responsive transcription factors such
      as Ste12, Tec1, and Flo8 are known to mediate filamentation-specific
      transcription. We were interested in investigating the translational regulation
      of specific mRNAs during the yeast-to-hyphal-form transition. Using polyribosome
      fractionation and RT-PCR analysis, we identified STE12, GPA2, and CLN1 as
      translation regulation target genes during filamentous growth. The transcript
      levels for these genes did not change, but their mRNAs were preferentially
      associated with polyribosomes during the hyphal transition. The intracellular
      levels of Ste12, Gpa2, and Cln1 proteins increased under hyphal-growth
      conditions. The increase in Ste12 protein level was partially blocked by
      mutations in the CAF20 and DHH1 genes, which encode an eIF4E inhibitor and a
      decapping activator, respectively. In addition, the caf20 and dhh1 mutations
      resulted in defects in filamentous growth. The filamentation defects caused by
      caf20 and dhh1 mutations were suppressed by STE12 overexpression. These results
      suggest that Caf20 and Dhh1 control yeast filamentation by regulating STE12
      translation.

PMID- 17041187
TI  - Skp1p regulates Soi3p/Rav1p association with endosomal membranes but is not
      required for vacuolar ATPase assembly.
AB  - Skp1p is an essential component of SCF-type E3 ubiquitin ligase complexes and
      associates with these through binding to F-box proteins. Skp1p also binds F-box
      proteins in a number of non-SCF complexes. The Skp1p-associated yeast protein
      Soi3p/Rav1p (hereafter referred to as Rav1p) is a component of the RAVE complex
      required for regulated assembly of vacuolar ATPase (V-ATPase). Rav1p is also
      involved in transport of TGN proteins and endocytic cargo between early and late
      endosomes. To evaluate the role of Skp1p in the RAVE complex, we made use of the
      fact that overexpression of Rav1p is toxic because it sequesters Skp1p from
      essential interactions. We isolated a separation of function allele of SKP1,
      skp1(Asn108Tyr), that completely abrogated the Rav1p interaction but allowed
      Skp1p to perform other essential cellular functions. Cells containing the
      skp1(Asn108Tyr) allele as the sole source of Skp1p exhibited normal V-ATPase
      assembly and activity. However, in the skp1(Asn108Tyr) mutant strain, the
      membrane-associated pool of Rav1-green fluorescent protein was increased,
      suggesting that Skp1p is important for the release of Rav1p from endosomal
      membranes where it functions in V-ATPase assembly. Thus, although part of the
      RAVE complex, Skp1p does not appear to be involved in V-ATPase assembly but
      instead in the cycling of the complex off membranes. This work also provides a
      generalizable approach to defining the roles of interactions of Skp1p with
      individual F-box proteins through the isolation of special alleles of SKP1.

PMID- 17041188
TI  - Pheromone-induced degradation of Ste12 contributes to signal attenuation and the
      specificity of developmental fate.
AB  - The Ste12 transcription factor of Saccharomyces cerevisiae regulates
      transcription programs controlling two different developmental fates. One is
      differentiation into a mating-competent form that occurs in response to mating
      pheromone. The other is the transition to a filamentous-growth form that occurs
      in response to nutrient deprivation. These two distinct roles for Ste12 make it a
      focus for studies into regulatory mechanisms that impart biological specificity.
      The transient signal characteristic of mating differentiation led us to test the
      hypothesis that regulation of Ste12 turnover might contribute to attenuation of
      the mating-specific transcription program and restrict activation of the
      filamentation program. We show that prolonged pheromone induction leads to
      ubiquitin-mediated destabilization and decreased amounts of Ste12. This depletion
      in pheromone-stimulated cultures is dependent on the mating-pathway-dedicated
      mitogen-activated protein kinase Fus3 and its target Cdc28 inhibitor, Far1.
      Attenuation of pheromone-induced mating-specific gene transcription (FUS1)
      temporally correlates with Ste12 depletion. This attenuation is abrogated in the
      deletion backgrounds (fus3Delta or far1Delta) where Ste12 is found to persist.
      Additionally, pheromone induces haploid invasion and filamentous-like growth
      instead of mating differentiation when Ste12 levels remain high. These
      observations indicate that loss of Ste12 reinforces the adaptive response to
      pheromone and contributes to the curtailing of a filamentation response.

PMID- 17041189
TI  - Binding specificities and potential roles of isoforms of eukaryotic initiation
      factor 4E in Leishmania.
AB  - The 5' cap structure of trypanosomatid mRNAs, denoted cap 4, is a complex
      structure that contains unusual modifications on the first four nucleotides. We
      examined the four eukaryotic initiation factor 4E (eIF4E) homologues found in the
      Leishmania genome database. These proteins, denoted LeishIF4E-1 to LeishIF4E-4,
      are located in the cytoplasm. They show only a limited degree of sequence
      homology with known eIF4E isoforms and among themselves. However, computerized
      structure prediction suggests that the cap-binding pocket is conserved in each of
      the homologues, as confirmed by binding assays to m(7)GTP, cap 4, and its
      intermediates. LeishIF4E-1 and LeishIF4E-4 each bind m(7)GTP and cap 4 comparably
      well, and only these two proteins could interact with the mammalian eIF4E binding
      protein 4EBP1, though with different efficiencies. 4EBP1 is a translation
      repressor that competes with eIF4G for the same residues on eIF4E; thus,
      LeishIF4E-1 and LeishIF4E-4 are reasonable candidates for serving as translation
      factors. LeishIF4E-1 is more abundant in amastigotes and also contains a typical
      3' untranslated region element that is found in amastigote-specific genes.
      LeishIF4E-2 bound mainly to cap 4 and comigrated with polysomal fractions on
      sucrose gradients. Since the consensus eIF4E is usually found in 48S complexes,
      LeishIF4E-2 could possibly be associated with the stabilization of trypanosomatid
      polysomes. LeishIF4E-3 bound mainly m(7)GTP, excluding its involvement in the
      translation of cap 4-protected mRNAs. It comigrates with 80S complexes which are
      resistant to micrococcal nuclease, but its function is yet unknown. None of the
      isoforms can functionally complement the Saccharomyces cerevisiae eIF4E,
      indicating that despite their structural conservation, they are considerably
      diverged.

PMID- 17041191
TI  - Intratumoral heterogeneity of her-2/neu in invasive mammary carcinomas using
      fluorescence in-situ hybridization and tissue microarray.
AB  - Fluorescence in-situ hybridization is increasingly being used to determine HER
      2/neu status in patients with breast carcinoma. The possibility that intratumoral
      heterogeneity of HER-2/neu gene amplification may potentially contribute to
      inaccurate assessment of HER-2/neu status was investigated in routine cases of
      invasive mammary carcinomas. From 169 representative formalin-fixed, paraffin
      embedded blocks of invasive duct mammary carcinomas with grade 3 architecture, 48
      cases were analyzed by fluorescence in-situ hybridization and 59 analyses were
      performed. Intratumoral heterogeneity for HER-2/neu gene amplification was
      demonstrated in only 5 (16%) of 31 cases where morphologically similar areas of a
      single tumor were analyzed. We conclude from this study that intratumoral
      heterogeneity of HER-2/neu gene amplification is a demonstrable but relatively
      uncommon occurrence. For invasive mammary carcinomas, the accurate assessment of
      HER-2/neu status by fluorescence in-situ hybridization analysis is not
      significantly confounded by intratumoral heterogeneity of HER-2/neu gene
      amplification in individual tumors.

PMID- 17041190
TI  - Transcriptional regulation of MDR1, encoding a drug efflux determinant, in
      fluconazole-resistant Candida albicans strains through an Mcm1p binding site.
AB  - Constitutive, high-level transcription of the gene encoding the drug efflux
      facilitator Mdr1p is commonly observed in laboratory and clinical strains of
      Candida albicans that are resistant to the antifungal drug fluconazole (FLC). In
      five independently isolated FLC(R) laboratory strains, introduction of a wild
      type MDR1 promoter fragment fused to the yeast enhanced green fluorescent protein
      (yEGFP) reporter gene resulted in high-level expression of GFP, demonstrating
      that overexpression of MDR1 is dependent on a trans-acting factor. This study
      identified a 35-bp MDR1 promoter element, termed the MDRE, that mediates high
      level MDR1 transcription. When inserted into a heterologous promoter, the MDRE
      was sufficient to mediate high-level expression of the yEGFP reporter gene
      specifically in MDR1 trans-activation strains. The MDRE promoted transcription in
      an orientation-independent and dosage-dependent manner. Deletion of the MDRE in
      the full-length promoter did not abolish MDR1 trans-activation, indicating that
      elements upstream of the MDRE also contribute to transcription of MDR1 in these
      overexpression strains. Analysis of the MDRE sequence indicated that it contains
      an Mcm1p binding site very similar in organization to the site seen upstream of
      the Saccharomyces cerevisiae MFA1 and STE2 genes. Electrophoretic mobility shift
      analysis demonstrated that both wild-type, FLC-sensitive and MDR1 trans
      activated, FLC-resistant strains contain a factor that binds the MDRE. Depletion
      of Mcm1p, by use of a strain in which MCM1 expression is under the control of a
      regulated promoter (44), resulted in a loss of MDRE binding activity. Thus, the
      general transcription factor Mcm1p participates in the regulation of MDR1
      expression.

PMID- 17041192
TI  - Critical comparison of 31 commercially available digital slide systems in
      pathology.
AB  - Advances in new technologies for complete slide digitization in pathology have
      allowed the appearance of a wide spectrum of technologic solutions for whole
      slide scanning, which have been classified into motorized microscopes and
      scanners. This article describes technical aspects of 31 different digital
      microscopy systems. The most relevant characteristics of the scanning devices are
      described, including the cameras used, the speed of digitization, and the image
      quality. Other aspects, such as the file format, the compression techniques, and
      the solutions for visualization of digital slides, (including diagnosis-aided
      tools) are also considered. Most of the systems evaluated allow a high-resolution
      digitization of the whole slide within about 1 hour using a x40 objective. The
      image quality of the current virtual microscopy systems is suitable for clinical,
      educational, and research purposes. The efficient use of digital microscopy by
      means of image analysis systems can offer important benefits to pathology
      departments.

PMID- 17041193
TI  - Predicting sentinel lymph node metastases in infiltrating breast carcinoma with
      vascular invasion.
AB  - Sentinel lymph node and clinically negative axillary node status was compared
      with well-known clinicopathological characteristics such as tumor size,
      histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER
      2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph
      nodes were found in 29 of 100 patients: 19 with metastases detected by
      hematoxylin and eosin staining and 10 with micrometastases confirmed by
      immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present
      in larger carcinomas (P < 0.03), more frequently in tumors with negative PR
      status (P < 0.037) and evident lymphovascular invasion (P < 0.002).
      Lymphovascular invasion was also associated with breast cancer of higher
      histologic (P = 0.011) and nuclear grade (P = 0.039). Tumor size and the presence
      of lymphovascular invasion were found to be significant predictors of
      pathologically positive sentinel lymph node in T1 and T2.

PMID- 17041194
TI  - The correlation between the tumor necrosis and renal artery changes in renal cell
      carcinoma.
AB  - Necrosis, cysts, hemorrhage, and calcification represent common findings in renal
      cell carcinoma. Different lesions, including arteriosclerosis or fibromuscular
      dysplasia, or both, may involve the main renal artery. This study analyzed the
      relationship between the presence and extent of necrosis in renal cell carcinoma
      with renal artery changes in a consecutive series of 112 patients (71 men, 41
      women) with mean renal cell carcinoma of 7.7 cm (range, 2 to 20 cm). Necrosis was
      seen macroscopically and confirmed microscopically in 88 cases (78.6%), with 64
      tumors having less than 50% and 24 more than 50% necrosis. Fibromuscular
      dysplasia was found in 41 patients (36.6%; 17 men, 24 women) and atherosclerotic
      changes in 21 patients (18.8%; 18 men, 3 women). The results suggest that
      necrosis of renal cell carcinoma was significantly more common in women with
      associated fibromuscular dysplasia (especially type I) and men with
      atherosclerotic changes of renal artery.

PMID- 17041196
TI  - Images in pathology. Endometrial stromal sarcoma with hyalinizing giant rosettes
      and separate leiomyoma with palisading nuclei in the same uterus.

PMID- 17041195
TI  - Benign schwannoma with perineurioma-like areas: A clinicopathologic study of 11
      cases.
AB  - Eleven schwannomas are described. All tumors were well demarcated and surrounded
      by a true capsule or pseudocapsule and manifested Antoni A and Antoni B areas,
      Verocay bodies, and hyalinized vessels. In addition to typical schwannoma, there
      were clear cell areas composed of spindled cells arranged either in parallel
      sheets or in loops within the myxoid matrix, morphologically identical to
      retiform (reticular) perineurioma. The Schwann cells in the conventional
      schwannomatous areas displayed typical ultrastructural features. Those comprising
      the perineurioma-like areas revealed a primitive morphology. They were slender or
      polygonal and were devoid of an external lamina, pinocytic vesicles, or
      junctions. These findings suggest that the perineurioma-like areas consist of
      primitive or modified Schwann cells, or, alternatively, these perineurioma-like
      areas represent true, but incomplete perineurial differentiation within otherwise
      ordinary benign schwannomas. These neoplasms represent a morphologic variant of
      schwannoma having distinctive perineurial-like areas, a pattern which may elicit
      diagnostic difficulties.

PMID- 17041198
TI  - Images in pathology. Histiocytic lymphadenopathy secondary to metallosis
      following hip replacement.

PMID- 17041199
TI  - Images in pathology. Spontaneous coronary artery dissection as cause of sudden
      cardiac death in a young woman with oral contraceptive use.

PMID- 17041200
TI  - Images in pathology. Glomangioma of the sural nerve.

PMID- 17041202
TI  - Images in pathology. Invasive squamous cell carcinoma of vulva that wanted to be
      a puppy.

PMID- 17041203
TI  - Synchronous sporadic carcinoma and primary hyperplasia of the parathyroid glands:
      A case report and review of the literature.
AB  - Parathyroid carcinoma is the least common endocrine malignancy. Although it has
      been noted to be associated with certain clinical factors, such as familial hyper
      parathyroidism, its etiology remains unknown. In rare instances, particularly in
      patients with chronic renal failure, it has been proposed that parathyroid
      carcinoma can arise from malignant transformation of benign lesions. We present a
      case of synchronous malignant and primary hyperplastic parathyroid disease in a
      patient with normal renal function. A 46-year-old woman was seen with symptomatic
      refractory hypercalcemia. Investigations suggested a hyperactive parathyroid
      gland. Operative findings were of a low-grade parathyroid carcinoma in
      concurrence with diffuse hyperplasia of the remaining glands. To our knowledge
      this represents the fifth reported case. The possibility of malignant change in
      hyperplastic parathyroid tissue has implications for patient management and
      follow-up, particularly if tissue is left in situ to maintain hormonal function.

PMID- 17041204
TI  - Epithelioid hemangioendothelioma of the spinal cord: Description of a case with
      cytogenetic analysis.
AB  - A case of epithelioid hemangioendothelioma of the cauda equina is reported. The
      patient presented with rapidly worsening low back pain. Magnetic resonance
      imaging revealed a sharply demarcated intradural lumbar lesion. A bluish-red
      lesion, attached to the filum terminale, was removed. The patient is alive
      without evidence of recurrence 18 months after surgery. The tumor was composed of
      variously sized vessels lined by epithelioid endothelial cells with clear
      cytoplasm and centrally located, moderately atypical nuclei. These cells were
      immunoreactive for CD31 and factor VIII antibodies. Cytogenetic analysis
      disclosed two clones: 44-45X, - Y [cp3]/46XY[11]. Epithelioid
      hemangioendothelioma may arise in several sites, the most common being soft
      tissues. It is a borderline tumor that may recur, may metastasize, and rarely
      causes death. The present case appears to be the first example of epithelioid
      hemangioendothelioma of the spinal cord.

PMID- 17041205
TI  - Leydig cell tumor of the testis with histological and immunohistochemical
      features of malignancy in a 1-year-old boy with isosexual pseudoprecocity.
AB  - The article reports the clinical, histopathological, and immunohistochemical
      findings of a 1-year-old boy presenting with isosexual pseudoprecocity
      attributable to a functioning Leydig cell tumor of the testis. The case appears
      to represent the youngest patient ever recognized with this well-known syndrome.
      Malignancy features were also for the first time initially assessed using
      criteria, retrospectively developed from the literature, for metastasizing Leydig
      cell tumor. All the following were found: infiltrative borders, cellular
      pleomorphism, high mitotic index (12-14/high-power field), high MIB-1 index
      (40%), P53 positivity in 50% of the cells, and bcl-2 positivity in 15% of the
      cells. Immunohistochemistry proved the cells of the tumor to be positive for
      inhibin, Melan-A, synaptophysin, cytokeratin, and calretinin and negative for S
      100 and chromogranin A. Notably, lipochrome and crystals of Reinke were not found
      in the tumor cells. Although the neoplasm fulfilled the criteria for a
      potentially metastasizing Leydig cell tumor, there was no evidence of that event
      having occurred, perhaps as a result of early treatment or as indication that
      criteria developed for Leydig cell tumor of adults may not apply to children.

PMID- 17041206
TI  - Isolated hepatic involvement of cat scratch disease in immunocompetent adults:
      Enhanced magnetic resonance imaging, pathological findings, and molecular
      analysis--two cases.
AB  - Visceral involvement in absence of lymphadenopathy is a rare manifestation in cat
      scratch disease; hepatic granulomas are rare, representing 0.3% of systemic
      manifestations of cat scratch disease, and gallbladder extension is a singular
      case. The present article refers to 2 rare cases of visceral cat scratch disease
      in immunocompetent adults with hepatic granulomatous inflammation, caused by
      Bartonella henselae infection, with gallbladder involvement in 1 case and no
      lymphadenopathy. Histological features demonstrated the presence of inflammatory
      necrotizing granulomatous nonneoplastic process. Molecular studies (polymerase
      chain reaction) were performed to confirm the infectious etiology.

PMID- 17041207
TI  - Ectopic modified sebaceous glands in human penis.
AB  - The balanopreputial sulcus is believed to be the most frequent site of the so
      called Tyson's glands. The intriguing feature of these anatomical structures is
      their mere existence, which has been doubted. Herein, the authors present a case
      of a 24-year-old man who underwent surgical treatment of his phimosis. On
      microscopic examination of the specimen, glands with morphological features
      similar to those described by Tyson were noted.

PMID- 17041211
TI  - Molecular evolution of hepatitis B virus over 25 years.
AB  - Determining the longitudinal molecular evolution of hepatitis B virus (HBV) is
      difficult due to HBV's genomic complexity and the need to study paired samples
      collected over long periods of time. In this study, serial samples were collected
      from eight hepatitis B virus e antigen-negative asymptomatic carriers of HBV
      genotype B in 1979 and 2004, thus providing a 25-year period to document the long
      term molecular evolution of HBV. The rate, nature, and distribution of mutations
      that emerged over 25 years were determined by phylogenetic and linear regression
      analysis of full-length HBV genome sequences. Nucleotide hypervariability was
      observed within the polymerase and pre-S/S overlap region and within the core
      gene. The calculated mean number of nucleotide substitutions/site/year (7.9 x 10(
      5)) was slightly higher than published estimates (1.5 x 10(-5) to 5 x 10(-5)).
      Nucleotide changes in the quasispecies population did not significantly alter the
      molecular evolutionary rate, based on linear regression analysis of evolutionary
      distances among serial clone pre-S region sequences. Therefore, the directly
      amplified or dominant sequence was sufficient to estimate the putative molecular
      evolutionary rate for these long-term serial samples. On average, the ratio of
      synonymous (dS) to nonsynonymous (dN) substitutions was highest for the
      polymerase-coding region and lowest for the core-coding region. The low dS/dN
      ratios observed within the core suggest that selection occurs within this gene
      region, possibly as an immune evasion strategy. The results of this study suggest
      that HBV sequence divergence may occur more rapidly than previously estimated, in
      a host immune phase-dependent manner.

PMID- 17041210
TI  - Nonsegmented negative-strand viruses as vaccine vectors.

PMID- 17041212
TI  - Identifying epitopes responsible for neutralizing antibody and DC-SIGN binding on
      the spike glycoprotein of the severe acute respiratory syndrome coronavirus.
AB  - The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) uses
      dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) to facilitate cell
      entry via cellular receptor-angiotensin-converting enzyme 2. For this project, we
      used recombinant baculoviruses expressing different lengths of SARS-CoV spike (S)
      protein in a capture assay to deduce the minimal DC-SIGN binding region. Our
      results identified the region location between amino acid (aa) residues 324 to
      386 of the S protein. We then generated nine monoclonal antibodies (MAbs) against
      the S protein to map the DC-SIGN-binding domain using capture assays with
      pseudotyped viruses and observed that MAb SIa5 significantly blocked S protein-DC
      SIGN interaction. An enhancement assay using the HKU39849 SARS-CoV strain and
      human immature dendritic cells confirmed our observation. Data from a pepscan
      analysis and M13 phage peptide display library system mapped the reactive MAb
      SIa5 epitope to aa residues 363 to 368 of the S protein. Results from a capture
      assay testing three pseudotyped viruses with mutated N-linked glycosylation sites
      of the S protein indicate that only two pseudotyped viruses (N330Q and N357Q,
      both of which lost glycosylation sites near the SIa5 epitope) had diminished DC
      SIGN-binding capacity. We also noted that MAb SIb4 exerted a neutralizing effect
      against HKU39849; its reactive epitope was mapped to aa residues 435 to 439 of
      the S protein. We offer the data to facilitate the development of therapeutic
      agents and preventive vaccines against SARS-CoV infection.

PMID- 17041213
TI  - Postentry events are responsible for restriction of productive varicella-zoster
      virus infection in Chinese hamster ovary cells.
AB  - Productive infection of varicella-zoster virus (VZV) in vitro is restricted
      almost exclusively to cells derived from humans and other primates. We
      demonstrate that the restriction of productive VZV infection in CHO-K1 cells
      occurs downstream of virus entry. Entry of VZV into CHO-K1 cells was
      characterized by utilizing an ICP4/beta-galactosidase reporter gene that has been
      used previously to study herpes simplex virus type 1 entry. Entry of VZV into CHO
      K1 cells involved cell surface interactions with heparan sulfate
      glycosaminoglycans and a cation-independent mannose-6-phosphate receptor.
      Lysosomotropic agents inhibited the entry of VZV into CHO-K1 cells, consistent
      with a low-pH-dependent endocytic mechanism of entry. Infection of CHO-K1 cells
      by VZV resulted in the production of both immediate early and late gene products,
      indicating that a block to progeny virus production occurs after the initiation
      of virus gene expression.

PMID- 17041214
TI  - Administration of fludarabine-loaded autologous red blood cells in simian
      immunodeficiency virus-infected sooty mangabeys depletes pSTAT-1-expressing
      macrophages and delays the rebound of viremia after suspension of antiretroviral
      therapy.
AB  - A major limitation of highly active antiretroviral therapy is that it fails to
      eradicate human immunodeficiency virus (HIV) infection due to its limited effects
      on viral reservoirs carrying replication-competent HIV, including
      monocytes/macrophages (M/M). Therefore, therapeutic approaches aimed at targeting
      HIV-infected M/M may prove useful in the clinical management of HIV-infected
      patients. In previous studies, we have shown that administration of fludarabine
      loaded red blood cells (RBC) in vitro selectively induces cell death in HIV
      infected M/M via a pSTAT1-dependent pathway. To determine the in vivo efficacy of
      this novel therapeutic strategy, we treated six naturally simian immunodeficiency
      virus (SIV)-infected sooty mangabeys (SMs) with either 9-[2-(R)
      (phosphonomethoxy)propyl]adenine (PMPA) only, fludarabine-loaded RBC only, or
      PMPA in association with fludarabine-loaded RBC. The rationale of this treatment
      was to target infected M/M with fludarabine-loaded RBC at a time when PMPA is
      suppressing viral replication taking place in activated CD4+ T cells. In vivo
      administration of fludarabine-loaded RBC was well tolerated and did not induce
      any discernible side effect. Importantly, addition of fludarabine-loaded RBC to
      PMPA delayed the rebound of viral replication after suspension of therapy, thus
      suggesting a reduction in the size of SIV reservoirs. While administrations of
      fludarabine-loaded RBC did not induce any change in the CD4+ or CD8+ T-cell
      compartments, we observed, in chronically SIV-infected SMs, a selective depletion
      of M/M expressing pSTAT1. This study suggests that therapeutic strategies based
      on the administration of fludarabine-loaded RBC may be further explored as
      interventions aimed at reducing the size of the M/M reservoirs during chronic HIV
      infection.

PMID- 17041216
TI  - Identification of major histocompatibility complex class II-restricted antigens
      and epitopes of the Epstein-Barr virus by a novel bacterial expression cloning
      approach.
AB  - Epstein-Barr virus (EBV)-specific T cells have been successfully used to treat or
      prevent EBV-positive lymphoproliferative disease in hematopoietic stem cell
      transplant recipients, but the antigens recognized by the infused CD4+ T cells
      have remained unknown. Here, we describe a simple procedure that permits the
      identification of viral T-helper (TH)-cell antigens and epitopes. This direct
      antigen identification method is based on the random expression of viral
      polypeptides fused to chloramphenicol acetyltransferase (CAT) in bacteria, which
      are subsequently fed to major histocompatibility complex class II+ antigen
      presenting cells and probed with antigen-specific T cells. The fusion of
      antigenic fragments to CAT offers several advantages. First, chloramphenicol
      treatment allows the selection of bacteria expressing antigen-CAT fusion proteins
      in frame, which greatly reduces the number of colonies to be screened. Second,
      antigenic fragments fused to CAT are expressed at high levels, even when derived
      from proteins that are toxic to bacteria. Third, the uniformly high expression
      level of antigen-CAT fusion proteins permits the establishment of large and
      representative pool sizes. Finally, antigen identification does not require
      knowledge of the restriction element and often leads directly to the
      identification of the T-cell epitope. Using this approach, the BALF4 and BNRF1
      proteins were identified as targets of the EBV-specific T-helper-cell response,
      demonstrating that lytic cycle antigens are a relevant component of the EBV
      specific TH-cell response.

PMID- 17041215
TI  - Host cell DNA repair pathways in adeno-associated viral genome processing.
AB  - Recentstudies have shown that wild-type and recombinant adeno-associated virus
      (AAV and rAAV) genomes persist in human tissue predominantly as double-stranded
      (ds) circular episomes derived from input linear single-stranded virion DNA.
      Using self-complementary recombinant AAV (scAAV) vectors, we generated
      intermediates that directly transition to ds circular episomes. The scAAV genome
      ends are palindromic hairpin-structured terminal repeats, resembling a double
      stranded break repair intermediate. Utilizing this substrate, we found cellular
      DNA recombination and repair factors to be essential for generating circular
      episomal products. To identify the specific cellular proteins involved, the scAAV
      circularization-dependent vector was used as a reporter in 19 mammalian DNA
      repair-deficient cell lines. The results show that RecQ helicase family members
      (BLM and WRN), Mre11 and NBS1 of the Mre11-Rad50-Nbs1 (MRN) complex, and ATM are
      required for efficient scAAV genome circularization. We further demonstrated that
      the scAAV genome requires ATM and DNA-PK(CS), but not NBS1, to efficiently
      convert to a circular form in nondividing cells in vivo using transgenic mice.
      These studies identify specific pathways involved for further elucidating viral
      and cellular mechanisms of DNA maintenance important to the viral life cycle and
      vector utilizations.

PMID- 17041217
TI  - Antilipopolysaccharide factor interferes with white spot syndrome virus
      replication in vitro and in vivo in the crayfish Pacifastacus leniusculus.
AB  - In a study of genes expressed differentially in the freshwater crayfish
      Pacifastacus leniusculus infected experimentally with the white spot syndrome
      virus (WSSV), one protein, known as antilipopolysaccharide factor (ALF), was
      chosen, among those whose transcript levels increased upon viral infection, for
      further studies. ALF RNA interference (RNAi) experiments in whole animals and in
      cell cultures indicated that ALF can protect against WSSV infection, since
      knockdown of ALF by RNAi specifically resulted in higher rates of viral
      propagation. In a cell culture of hematopoietic tissue (Hpt) from P. leniusculus,
      quantitative PCR showed that knockdown of ALF by RNAi resulted into WSSV levels
      that were about 10-fold higher than those treated with control double-stranded
      RNA (dsRNA). In addition, RNAi experiments with other crayfish genes that had
      been found to be up-regulated by a WSSV infection did not result in any changes
      of viral loads. Thus, the cell culture does not respond to dsRNA in a similar
      manner, as shown earlier for dsRNA injected into shrimp, which gave a higher
      degree of resistance to WSSV infection. If ALF transcription in whole animals was
      stimulated by the administration of UV-treated WSSV, a partial protection against
      a subsequent challenge with the active virus was conferred to the host. This is
      the first crustacean gene product identified with the capacity to interfere with
      replication of this important pathogen.

PMID- 17041218
TI  - Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs.
AB  - We evaluated the gnotobiotic (Gn) pig as a model to study the pathogenesis of
      human norovirus (HuNoV) and to determine the target cells for viral replication.
      Sixty-five Gn pigs were inoculated with fecal filtrates of the
      NoV/GII/4/HS66/2001/US strain or with pig-passaged intestinal contents (IC) and
      euthanized acutely (n = 43) or after convalescence (n = 22). Age-matched Gn
      piglets (n = 14) served as mock-inoculated controls. Seventy-four percent (48/65)
      of the inoculated animals developed mild diarrhea compared to 0 of 14 controls.
      Pigs from postinoculation days (PID) 1 to 4 tested positive for HuNoV by reverse
      transcription-PCR of rectal swab fluids (29/65) and IC (9/43) and by antigen (Ag)
      enzyme-linked immunosorbent assay (ELISA) using antiserum to virus-like particles
      of HuNoV GII/4. No control pigs were positive. Histopathologic examination showed
      mild lesions in the proximal small intestine of only one pig (1/7).
      Seroconversion after PID 21 was detected by antibody ELISA in 13 of 22 virus
      inoculated pigs (titers, 1:20 to 1:200) but not in controls. Immunofluorescent
      microscopy using a monoclonal antibody to HuNoV GII capsid revealed patchy
      infection of duodenal and jejunal enterocytes of 18 of 31 HuNoV-inoculated pigs
      with a few stained cells in the ileum and no immunofluorescence (IF) in mock
      inoculated controls. Immunofluorescent detection of the viral nonstructural N
      terminal protein antigen in enterocytes confirmed translation. Transmission
      electron microscopy of intestines from HuNoV-inoculated pigs showed disrupted
      enterocytes, with cytoplasmic membrane vesicles containing calicivirus-like
      particles of 25 to 40 nm in diameter. In summary, serial passage of HuNoV in
      pigs, with occurrence of mild diarrhea and shedding, and immunofluorescent
      detection of the HuNoV structural and nonstructural proteins in enterocytes
      confirm HuNoV replication in Gn pigs.

PMID- 17041219
TI  - Murine hepatitis virus strain 1 produces a clinically relevant model of severe
      acute respiratory syndrome in A/J mice.
AB  - Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease
      which has been difficult to study and treat because of the lack of a readily
      available animal model. Intranasal infection of A/J mice with the coronavirus
      murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features
      of SARS. All MHV-1-infected A/J mice developed progressive interstitial
      pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline
      membranes, resulting in death of all animals. In contrast, other mouse strains
      developed only mild transitory disease. Infected A/J mice had significantly
      higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP
      1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore,
      FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly
      increased in the lungs of infected A/J mice. These animals developed a less
      robust type I interferon response to MHV-1 infection than resistant C57BL/6J
      mice, and treatment with recombinant beta interferon improved survival. This
      study describes a potentially useful small animal model of human SARS, defines
      its pathogenesis, and suggests treatment strategies.

PMID- 17041220
TI  - Human immunodeficiency virus type 1 Gag polyprotein modulates its own
      translation.
AB  - The full-length viral RNA of human immunodeficiency virus type 1 (HIV-1)
      functions both as the mRNA for the viral structural proteins Gag and Gag/Pol and
      as the genomic RNA packaged within viral particles. The packaging signal which
      Gag recognizes to initiate genome encapsidation is in the 5' untranslated region
      (UTR) of the HIV-1 RNA, which is also the location of translation initiation
      complex formation. Hence, it is likely that there is competition between the
      translation and packaging processes. We studied the ability of Gag to regulate
      translation of its own mRNA. Gag had a bimodal effect on translation from the HIV
      1 5' UTR, stimulating translation at low concentrations and inhibiting
      translation at high concentrations in vitro and in vivo. The inhibition was
      dependent upon the ability of Gag to bind the packaging signal through its
      nucleocapsid domain. The stimulatory activity was shown to depend on the matrix
      domain of Gag. These results suggest that Gag controls the equilibrium between
      translation and packaging, ensuring production of enough molecules of Gag to make
      viral particles before encapsidating its genome.

PMID- 17041221
TI  - Regulation of inducible nitric oxide synthase expression by viral A238L-mediated
      inhibition of p65/RelA acetylation and p300 transactivation.
AB  - Uncontrolled generation of nitric oxide (NO) by inducible nitric-oxide synthase
      (iNOS) can cause damage to host cells and inflammation, two undesirable events
      for virus spreading. African swine fever virus (ASFV) infection regulates iNOS
      induced gene expression through the synthesis of the A238L virus protein. We here
      explored the role of A238L, an NF-kappaB and NFAT inhibitor, in the regulation of
      iNOS transcription in macrophages. NO production and iNOS mRNA and protein levels
      as well as iNOS promoter activity after lipopolysaccharide (LPS)-gamma interferon
      (IFN-gamma) treatment were down-regulated both during ASFV infection and in Raw
      264.7 cells stably expressing the viral protein. Overexpression of p300, but not
      of a histone acetyltransferase (HAT) defective mutant, reverted the A238L
      mediated inhibition of both basal and LPS-IFN-gamma-induced iNOS promoter
      activity. Following stimulation with LPS-IFN-gamma, p65 and p300 interaction was
      abolished in Raw-A238L cells. Expression of A238L also inhibited p65/relA and
      p300 binding to the distal NF-kappaB sequence of the iNOS promoter together with
      p65 acetylation. Finally, A238L abrogated p300 transactivation mediated by a GAL4
      p300 construction. These results provide evidence for an unique viral mechanism
      involved in transcriptional regulation of iNOS gene expression.

PMID- 17041222
TI  - Macrophage transcriptional responses following in vitro infection with a highly
      virulent African swine fever virus isolate.
AB  - We used a porcine microarray containing 2,880 cDNAs to investigate the response
      of macrophages to infection by a virulent African swine fever virus (ASFV)
      isolate, Malawi LIL20/1. One hundred twenty-five targets were found to be
      significantly altered at either or both 4 h and 16 h postinfection compared with
      targets after mock infection. These targets were assigned into three groups
      according to their temporal expression profiles. Eighty-six targets showed
      increased expression levels at 4 h postinfection but returned to expression
      levels similar to those in mock-infected cells at 16 h postinfection. These
      encoded several proinflammatory cytokines and chemokines, surface proteins, and
      proteins involved in cell signaling and trafficking pathways. Thirty-four targets
      showed increased expression levels at 16 h postinfection compared to levels at 4
      h postinfection and in mock-infected cells. One host gene showed increased
      expression levels at both 4 and 16 h postinfection compared to levels in mock
      infected cells. The microarray results were validated for 12 selected genes by
      quantitative real-time PCR. Levels of protein expression and secretion were
      measured for two proinflammatory cytokines, interleukin 1beta and tumor necrosis
      factor alpha, during a time course of infection with either the virulent Malawi
      LIL20/1 isolate or the OUR T88/3 nonpathogenic isolate. The results revealed
      differences between these two ASFV isolates in the amounts of these cytokines
      secreted from infected cells.

PMID- 17041223
TI  - Integrity of membrane lipid rafts is necessary for the ordered assembly and
      release of infectious Newcastle disease virus particles.
AB  - Membrane lipid raft domains are thought to be sites of assembly for many
      enveloped viruses. The roles of both classical lipid rafts and lipid rafts
      associated with the membrane cytoskeleton in the assembly of Newcastle disease
      virus (NDV) were investigated. The lipid raft-associated proteins caveolin-1,
      flotillin-2, and actin were incorporated into virions, while the non-lipid raft
      associated transferrin receptor was excluded. Kinetic analyses of the
      distribution of viral proteins in lipid rafts, as defined by detergent-resistant
      membranes (DRMs), in non-lipid raft membranes, and in virions showed an
      accumulation of HN, F, and NP viral proteins in lipid rafts early after
      synthesis. Subsequently, these proteins exited the DRMs and were recovered
      quantitatively in purified virions, while levels of these proteins in detergent
      soluble cell fractions remained relatively constant. Cholesterol depletion of
      infected cells drastically altered the association of viral proteins with DRMs
      and resulted in an enhanced release of virus particles with reduced infectivity.
      Decreased infectivity was not due to effects on subsequent virus entry, since the
      extraction of cholesterol from intact virus did not significantly reduce
      infectivity. Particles released from cholesterol-depleted cells had very
      heterogeneous densities and altered ratios of NP and glycoproteins, demonstrating
      structural abnormalities which potentially contributed to their lowered
      infectivity. Taken together, these results indicate that lipid rafts, including
      cytoskeleton-associated lipid rafts, are sites of NDV assembly and that these
      domains are important for ordered assembly and release of infectious Newcastle
      disease virus particles.

PMID- 17041224
TI  - PmRab7 is a VP28-binding protein involved in white spot syndrome virus infection
      in shrimp.
AB  - Our aim was to isolate and characterize white spot syndrome virus (WSSV)-binding
      proteins from shrimp. After a blot of shrimp hemocyte membrane proteins was
      overlaid with a recombinant WSSV envelope protein (rVP28), the reactive bands on
      the blot were detected using anti-VP28 antibody. Among three membrane-associated
      molecules identified by liquid chromatography-tandem mass spectrometry, there was
      a 25-kDa protein that bound to both rVP28 and WSSV. Since it had a primary
      structure with high homology to the small GTP-binding protein Rab7, we named it
      Penaeus monodon Rab7 (PmRab7). The full-length PmRab7 cDNA was obtained, and
      results from a glutathione S-transferase pull-down assay confirmed specific
      binding to rVP28. Reverse transcriptase PCR analysis revealed PmRab7 expression
      in many tissues, and real-time PCR analysis revealed that expression was
      constitutive. Binding of PmRab7 to rVP28 or WSSV occurred in a dose-dependent
      manner and was inhibited by anti-Rab7 antibody. In an in vivo neutralization
      assay, the number of dead shrimp after challenge with WSSV plus PmRab7 (15%) or
      WSSV plus anti-Rab7 antibody (5%) was significantly lower than after challenge
      with WSSV alone (95%). In contrast to the WSSV-injected group, shrimp injected
      with WSSV plus PmRab7 or WSSV plus anti-Rab7 showed no WSSV-type histopathology.
      We conclude that PmRab7 is involved in WSSV infection in shrimp. This is the
      first study to identify a shrimp protein that binds directly to a major viral
      envelope protein of WSSV.

PMID- 17041225
TI  - At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo
      as active promoters for host nonrepetitive DNA transcription.
AB  - We report the first genome-wide comparison of in vivo promoter activities of a
      group of human-specific endogenous retroviruses in healthy and cancerous germ
      line tissues. To this end, we employed a recently developed technique termed
      genomic repeat expression monitoring. We found that at least 50% of human
      specific long terminal repeats (LTRs) possessed promoter activity, and many of
      them were up- or downregulated in a seminoma. Individual LTRs were expressed at
      markedly different levels, ranging from approximately 0.001 to approximately 3%
      of the housekeeping beta-actin gene transcript level. We demonstrated that the
      main factors affecting the LTR promoter activity were the LTR type (5'-proviral,
      3' proviral, or solitary) and position with regard to genes. The averaged
      promoter strengths of solitary and 3'-proviral LTRs were almost identical in both
      tissues, whereas 5'-proviral LTRs displayed two- to fivefold higher promoter
      activities. The relative content of promoter-active LTRs in gene-rich regions was
      significantly higher than that in gene-poor loci. This content was maximal in
      those regions where LTRs "overlapped" readthrough transcripts. Although many
      promoter-active LTRs were mapped near known genes, no clear-cut correlation was
      observed between transcriptional activities of genes and neighboring LTRs. Our
      data also suggest a selective suppression of transcription for LTRs located in
      gene introns.

PMID- 17041226
TI  - Human cytomegalovirus IE86 attenuates virus- and tumor necrosis factor alpha
      induced NFkappaB-dependent gene expression.
AB  - Human cytomegalovirus (HCMV) infection regulates a number of genes involved in
      the host antiviral response. We have previously reported that HCMV attenuates the
      expression of beta interferon (IFN-beta) and a number of proinflammatory
      chemokines, and this attenuation is mediated by the HCMV immediate-early protein
      IE86. The present study seeks to identify the mechanism by which IE86 blocks IFN
      beta expression. We demonstrate that the induction of IFN-beta during HCMV
      infection requires the activation of both the IRF-3 and the NFkappaB pathways.
      Therefore, IE86 may target either pathway to block IFN-beta expression. Our
      results show that IE86 does not block IRF-3 phosphorylation, dimerization,
      nuclear translocation, or target gene expression. However, using gel shift
      analysis, we demonstrate that IE86 efficiently inhibits virus-induced binding of
      NFkappaB to the IFN-beta promoter, resulting in attenuation of IFN-beta and
      NFkappaB-dependent gene expression. Furthermore, IE86 expression inhibits tumor
      necrosis factor alpha-induced NFkappaB DNA binding and target gene expression.
      Together, these results identify IE86 as a NFkappaB antagonist, which results in
      the suppression of NFkappaB-dependent cytokine and chemokine gene expression.

PMID- 17041227
TI  - JC virus minor capsid proteins Vp2 and Vp3 are essential for virus propagation.
AB  - Virus-encoded capsid proteins play a major role in the life cycles of all
      viruses. The JC virus capsid is composed of 72 pentamers of the major capsid
      protein Vp1, with one of the minor coat proteins Vp2 or Vp3 in the center of each
      pentamer. Vp3 is identical to two-thirds of Vp2, and these proteins share a DNA
      binding domain, a nuclear localization signal, and a Vp1-interacting domain. We
      demonstrate here that both the minor proteins and the myristylation site on Vp2
      are essential for the viral life cycle, including the proper packaging of its
      genome.

PMID- 17041229
TI  - Human papillomavirus genotype 31 does not express detectable microRNA levels
      during latent or productive virus replication.
AB  - It has recently become clear that several pathogenic DNA viruses express virally
      encoded microRNAs in infected cells. In particular, numerous microRNAs have been
      identified in a range of human and animal herpesviruses, and individual microRNAs
      have also been identified in members of the polyoma- and adenovirus families.
      Although their functions remain largely unknown, it seems likely that these viral
      microRNAs play an important role in viral replication in vivo. Here we present an
      analysis of the microRNAs expressed in human cells during the latent and
      productive phases of the human papillomavirus genotype 31 (HPV31) replication
      cycle. Although over 500 cellular microRNAs were cloned and identified, not a
      single HPV31-specific microRNA was obtained. We therefore concluded that HPV31,
      and possibly human papillomaviruses in general, does not express viral microRNAs.

PMID- 17041228
TI  - Novel envelope determinants for CCR3 use by human immunodeficiency virus.
AB  - Human immunodeficiency virus type 1 can generally use CCR3 and CCR5 for cell
      entry. We show that envelopes with novel phenotypes arise during "coreceptor
      switch": one loses the ability to use CCR3 (R5-only phenotype), and another gains
      use of CXCR4 in addition to CCR5 and CCR3 (R3/R5/X4-using phenotype). The
      envelope determinants for CCR3 use mapped to three amino acids. One, N356 in
      conserved region 3, is a potential glycosylation site and has not previously been
      associated with coreceptor use. The other two, R440 and N448 in conserved region
      4, are proximal to but distinct from residues already identified as being
      important for CCR5 binding.

PMID- 17041230
TI  - Genetic modifications of seizure susceptibility and expression by altered
      excitability in Drosophila Na(+) and K(+) channel mutants.
AB  - A seizure-paralysis repertoire characteristic of Drosophila "bang-sensitive"
      mutants can be evoked electroconvulsively in tethered flies, in which behavioral
      episodes are associated with synchronized spike discharges in different body
      parts. Flight muscle DLMs (dorsal longitudinal muscles) display a stereotypic
      sequence of initial and delayed bouts of discharges (ID and DD), interposed with
      giant fiber (GF) pathway failure and followed by a refractory period. We examined
      how seizure susceptibility and discharge patterns are modified in various K(+)
      and Na(+) channel mutants. Decreased numbers of Na(+) channels in nap(ts) flies
      drastically reduced susceptibility to seizure induction, eliminated ID, and
      depressed DD spike generation. Mutations of different K(+) channels led to
      differential modifications of the various components in the repertoire. Altered
      transient K(+) currents in Sh(133) and Hk mutants promoted ID induction. However,
      only Sh(133) but not Hk mutations increased DD seizure and GF pathway failure
      durations. Surprisingly, modifications in sustained K(+) currents in eag and Shab
      mutants increased thresholds for DD induction and GF pathway failure.
      Nevertheless, both eag and Shab, like Sh(133), increased DD spike generation and
      recovery time from GF pathway failure. Interactions between channel mutations
      with the bang-sensitive mutation bss demonstrated the role of membrane
      excitability in stress-induced seizure-paralysis behavior. Seizure induction and
      discharges were suppressed by nap(ts) in bss nap double mutants, whereas Sh
      heightened seizure susceptibility in bss Sh(133) and bss Sh(M) double mutants.
      Our results suggest that individual seizure repertoire components reflect
      different neural network activities that could be differentially altered by
      mutations of specific ion channel subunits.

PMID- 17041231
TI  - The occurrence and outcome of 39 pregnancies after 1621 cases of transcervical
      resection of endometrium.
AB  - BACKGROUND: To evaluate the outcomes and management of pregnancy after
      transcervical resection of the endometrium (TCRE). METHODS: Retrospective study
      of 39 pregnancies after 1621 procedures of TCRE. RESULTS: Among 1621 women who
      were successfully followed up after TCRE, there were 39 pregnancies in 32 women,
      including five ectopic pregnancies (12.8%) and 34 intrauterine pregnancies
      (87.2%). The majority of pregnancies (84.6%) occurred within the first 2 years.
      In the first year after TCRE, the incidence of pregnancy was 1.5%. In women who
      had amenorrhoea after TCRE, the chances of conception (2/676; 0.3%) were
      significantly (P < 0.001) lower than for those who continued to have period
      (30/945; 3.2%). Thirty-two cases with intrauterine pregnancy were terminated
      under ultrasound guidance with two difficult procedures. Only one pregnancy in
      our study resulted in spontaneous miscarriage which was managed by suction
      curettage. One term pregnancy had placenta increta resulting in Caesarean
      hysterectomy. CONCLUSIONS: Pregnancies after TCRE are associated with increased
      risk, and clinicians should be aware of the various complications of pregnancy
      that may occur after TCRE, including an increased risk of ectopic pregnancy.
      Surgical termination of pregnancy after TCRE is potentially a difficult procedure
      and should be carried out under ultrasound guidance.

PMID- 17041232
TI  - Can computers improve patient care by primary health care workers in India?
AB  - OBJECTIVE: The objective was to test whether a decision support technology for
      non-physicians can increase health care utilization and quality. DESIGN: Before
      and after measurements were taken from a systematic random sample of patients and
      staff at randomly assigned intervention and control facilities. SETTING: The
      study took place at primary health facilities in rural Tamil Nadu, India.
      PARTICIPANTS: One thousand two hundred and eighty-six patients and 82 staff were
      interviewed. INTERVENTION: A computer-assisted decision support technology was
      introduced to assist with patient screening. MAIN OUTCOME MEASURES: Outcome
      measures included new patient visits per month, a Global Patient Assessment of
      Care Index, and health worker attitude variables. RESULTS: There was a difference
      of difference of 430 new patient visits per month at the intervention sites (P =
      0.005), an increase from baseline of 18% at intervention sites compared with a
      decline of 5% at control sites. The intervention was associated with significant
      improvements in a Global Patient Assessment of Care Index (mean difference of
      difference 7.9, P < 0.001). The largest gains were made in patient communication,
      technical quality, and general satisfaction with care. The attitudes of public
      health workers toward the new technology and their jobs did not change.
      CONCLUSIONS: Decision support technologies have considerable potential to improve
      coverage and quality of health care for the poor and where there is no doctor,
      but the unreceptive attitude of public health workers would need to be overcome.
      Application of these technologies should take advantage of their popularity with
      patients and the opportunity to work through the private sector.

PMID- 17041233
TI  - A graph-based motif detection algorithm models complex nucleotide dependencies in
      transcription factor binding sites.
AB  - Given a set of known binding sites for a specific transcription factor, it is
      possible to build a model of the transcription factor binding site, usually
      called a motif model, and use this model to search for other sites that bind the
      same transcription factor. Typically, this search is performed using a position
      specific scoring matrix (PSSM), also known as a position weight matrix. In this
      paper we analyze a set of eukaryotic transcription factor binding sites and show
      that there is extensive clustering of similar k-mers in eukaryotic motifs, owing
      to both functional and evolutionary constraints. The apparent limitations of
      probabilistic models in representing complex nucleotide dependencies lead us to a
      graph-based representation of motifs. When deciding whether a candidate k-mer is
      part of a motif or not, we base our decision not on how well the k-mer conforms
      to a model of the motif as a whole, but how similar it is to specific, known k
      mers in the motif. We elucidate the reasons why we expect graph-based methods to
      perform well on motif data. Our MotifScan algorithm shows greatly improved
      performance over the prevalent PSSM-based method for the detection of eukaryotic
      motifs.

PMID- 17041234
TI  - Solution structure of a purine rich hexaloop hairpin belonging to PGY/MDR1 mRNA
      and targeted by antisense oligonucleotides.
AB  - A preferential target of antisense oligonucleotides directed against human
      PGY/MDR1 mRNA is a hairpin containing a stem with a G*U wobble pair, capped by
      the purine-rich 5'r(GGGAUG)3' hexaloop. This hairpin is studied by
      multidimensional NMR and restrained molecular dynamics, with special emphasis on
      the conformation of south sugars and non-standard phosphate linkages evidenced in
      both the stem and the loop. The hairpin is found to be highly structured. The G*U
      wobble pair, a strong counterion binding site, displays structural
      particularities that are characteristic of this type of mismatch. The upper part
      of the stem undergoes distortions that optimize its interactions with the
      beginning of the loop. The loop adopts a new fold in which the single-stranded
      GGGA purine tract is structured in A-like conformation stacked in continuity of
      the stem and displays an extensive hydrogen bonding surface for recognition. The
      remarkable hairpin stability results from classical inter- and intra-strand
      interactions reinforced by numerous hydrogen bonds involving unusual backbone
      conformations and ribose 2'-hydroxyl groups. Overall, this work emphasizes
      numerous features that account for the well-ordered structure of the whole
      hairpin and highlights the loop properties that facilitate interaction with
      antisense oligonucleotides.

PMID- 17041235
TI  - MMASS: an optimized array-based method for assessing CpG island methylation.
AB  - We describe an optimized microarray method for identifying genome-wide CpG island
      methylation called microarray-based methylation assessment of single samples
      (MMASS) which directly compares methylated to unmethylated sequences within a
      single sample. To improve previous methods we used bioinformatic analysis to
      predict an optimized combination of methylation-sensitive enzymes that had the
      highest utility for CpG-island probes and different methods to produce
      unmethylated representations of test DNA for more sensitive detection of
      differential methylation by hybridization. Subtraction or methylation-dependent
      digestion with McrBC was used with optimized (MMASS-v2) or previously described
      (MMASS-v1, MMASS-sub) methylation-sensitive enzyme combinations and compared with
      a published McrBC method. Comparison was performed using DNA from the cell line
      HCT116. We show that the distribution of methylation microarray data is
      inherently skewed and requires exogenous spiked controls for normalization and
      that analysis of digestion of methylated and unmethylated control sequences
      together with linear fit models of replicate data showed superior statistical
      power for the MMASS-v2 method. Comparison with previous methylation data for
      HCT116 and validation of CpG islands from PXMP4, SFRP2, DCC, RARB and TSEN2
      confirmed the accuracy of MMASS-v2 results. The MMASS-v2 method offers improved
      sensitivity and statistical power for high-throughput microarray identification
      of differential methylation.

PMID- 17041236
TI  - Association of -592C/A, -819C/T and -1082A/G interleukin-10 promoter
      polymorphisms with idiopathic recurrent spontaneous abortion.
AB  - Increasing evidence supports a role for altered T helper 1 (Th1)-Th2 cytokine
      balance in idiopathic recurrent spontaneous abortion (RSA). The aim of this study
      was to investigate the association of the interleukin 10 (IL-10) promoter
      polymorphisms -592C/A, -819C/T and -1082A/G with RSA. Women (n = 350) with at
      least three consecutive spontaneous abortions (RSA cases) and 200 control women
      with at least two successful pregnancies were included. The frequency of the 
      819T allele [P = 0.05, odds ratio (OR) = 1.51], but not other single-nucleotide
      polymorphisms (SNPs), was higher among RSA patients. Complete linkage
      disequilibrium (LD) was seen between -592C and -819C and -1082G alleles, as well
      as between -592A and -819T and between -819C and -1082G alleles only among
      patients. Although the genotype frequencies (except for -819C/C) of the three
      polymorphisms were comparable between patients and controls, higher frequency of 
      592A/-819T/-1082A haplotype (OR = 4.01, 95% CI = 1.83-7.95) was seen in cases
      versus controls. Regression analysis indicated that, after adjusting for
      potential variables, -592C/A (OR = 3.32, 95% CI = 1.76-6.27) and -819C/T (OR =
      5.06, 95% CI = 2.59-9.91) were associated with exclusively early but not
      exclusively late RSA, where negative association for both was noted. This
      supports the notion of involvement of IL-10-592C/A and -819C/T polymorphisms as
      inherited risk factors of idiopathic RSA.

PMID- 17041238
TI  - The combination of ultrasound with antibiotics released from bone cement
      decreases the viability of planktonic and biofilm bacteria: an in vitro study
      with clinical strains.
AB  - OBJECTIVES: Antibiotic-loaded bone cements are used for the permanent fixation of
      joint prostheses. Antibiotic-loaded cements significantly decrease the incidence
      of infection. The objective of this study was to investigate whether the
      viability of bacteria derived from patients with a prosthesis-related infection
      could be further decreased when antibiotic release from bone cements was combined
      with application of pulsed ultrasound. METHODS: Escherichia coli ATCC 10798,
      Staphylococcus aureus 7323, coagulase-negative staphylococci (CoNS 7368 and CoNS
      7391) and Pseudomonas aeruginosa 5148 were grown planktonically in suspension and
      as a biofilm on three different bone cements: Palacos R without gentamicin as
      control, gentamicin-loaded Palacos R-G and gentamicin/clindamycin-loaded Copal.
      The viability of planktonic and biofilm bacteria was measured in the absence and
      presence of pulsed ultrasound for 40 h. RESULTS: Ultrasound itself did not affect
      bacterial viability. However, application of pulsed ultrasound in combination
      with antibiotic release by antibiotic-loaded bone cements yielded a reduction of
      both planktonic and biofilm bacterial viability compared with antibiotic release
      without application of ultrasound. CONCLUSIONS: This study shows that antibiotic
      release in combination with ultrasound increases the antimicrobial efficacy
      further than antibiotic release alone against a variety of clinical isolates.
      Application of ultrasound in combination with antibiotic release in clinical
      practice could therefore lead to better prevention or treatment of prosthesis
      related infections.

PMID- 17041239
TI  - Number of X-ray examinations performed on paediatric and geriatric patients
      compared with adult patients.
AB  - The age of the patient is of prime importance when assessing the radiological
      risk to patients due to medical X-ray exposures and the total detriment to the
      population due to radiodiagnostics. In order to take into account the age
      specific radiosensitivity, three age groups are considered: children, adults and
      the elderly. In this work, the relative number of examinations carried out on
      paediatric and geriatric patients is established, compared with adult patients,
      for radiodiagnostics as a whole, for dental and medical radiology, for 8
      radiological modalities as well as for 40 types of X-ray examinations. The
      relative numbers of X-ray examinations are determined based on the corresponding
      age distributions of patients and that of the general population. Two broad
      groups of X-ray examinations may be defined. Group A comprises conventional
      radiography, fluoroscopy and computed tomography; for this group a paediatric
      patient undergoes half the number of examinations as that of an adult, and a
      geriatric patient undergoes 2.5 times more. Group B comprises angiography and
      interventional procedures; for this group a paediatric patient undergoes a one
      fourth of the number of examinations carried out on an adult, and a geriatric
      patient undergoes five times more.

PMID- 17041240
TI  - General guidelines for the assessment of internal dose from monitoring data:
      progress of the IDEAS project.
AB  - In recent major international intercomparison exercises on intake and internal
      dose assessments from monitoring data, the results calculated by different
      participants varied significantly. Based on this experience the need for
      harmonisation of the procedures has been formulated within an EU 5th Framework
      Programme research project. The aim of the project, IDEAS, is to develop general
      guidelines for standardising assessments of intakes and internal doses. The IDEAS
      project started in October 2001 and ended in June 2005. The project is closely
      related to some goals of the work of Committee 2 of the ICRP and since 2003 there
      has been close cooperation between the two groups. To ensure that the guidelines
      are applicable to a wide range of practical situations, the first step was to
      compile a database of well-documented cases of internal contamination. In
      parallel, an improved version of an existing software package was developed and
      distributed to the partners for further use. A large number of cases from the
      database was evaluated independently by the partners and the results reviewed.
      Based on these evaluations, guidelines were drafted and discussed with dosimetry
      professionals from around the world by means of a virtual workshop on the
      Internet early in 2004. The guidelines have been revised and refined on the basis
      of the experiences and discussions in this virtual workshop. The general
      philosophy of the Guidelines is presented here, focusing on the principles of
      harmonisation, optimisation and proportionality. Finally, the proposed Levels of
      Task to structure the approach of internal dose evaluation are reported.

PMID- 17041241
TI  - Disruption of neurofascin localization reveals early changes preceding
      demyelination and remyelination in multiple sclerosis.
AB  - Saltatory conduction in the nervous system is enabled through the intimate
      association between the leading edge of the myelin sheath and the axonal membrane
      to demarcate the node of Ranvier. The 186 kDa neuron specific isoform of the
      adhesion molecule neurofascin (Nfasc186) is required for the clustering of
      voltage gated Na+ channels at the node, whilst the 155 kDa glial specific isoform
      (Nfasc155) is required for the assembly of correct paranodal junctions. In order
      to understand the relationship between these vital structures and how they are
      affected in multiple sclerosis we have examined the expression of Nfasc155 and
      Nfasc186 in areas of inflammation, demyelination and remyelination from post
      mortem brains. Fourteen cases of neuropathologically confirmed multiple sclerosis
      (8 female and 6 male; post-mortem delay 7-24 h; age 37-77 years; and disease
      duration 15-40 years), comprising 20 tissue blocks with 32 demyelinating or
      remyelinating lesions, were used in this study. A significant early alteration in
      Nfasc155+ paranodal structures occurs within and adjacent to actively
      demyelinating white matter lesions that are associated with damaged axons. Shaker
      type Kv1.2 channels, normally located distally to the paranode, overlapped with
      the disrupted Nfasc155+ structures. In the absence of Nfasc155, Kv1.2 channels
      abutted normally clustered Nfasc186+ nodes, indicating that complete disruption
      of the paranodal structure and movement of Kv1.2 channels precede alterations at
      the node itself. Within areas of partial remyelination, a number of atypical
      triple-Nfasc155+ structures were noted that may represent transient
      oligodendrocyte-axonal contacts during the process of myelin repair or aberrant
      interactions. Within shadow plaques discretely clustered Na+v, Nfasc186+ and
      Nfasc155+ domains indicated the restoration of normal nodal architecture. The
      alterations in oligodendrocyte Nfasc155 expression that accompany inflammation
      and demyelination suggest an ongoing disruption to the axonal-oligodendrocyte
      complex within newly forming as well as established lesions in multiple
      sclerosis, resulting in destruction of the Nfasc186+/Na+v nodal complex vital to
      successful fast neurotransmission in the CNS.

PMID- 17041242
TI  - Mechanims of aerosol particle deposition in the Oro-pharynx under non-steady
      airflow.
AB  - Comparison of experimental and computational results of aerosol deposition in the
      oro-pharyngeal cast of human published recently (Sosnowski TR, Moskal A, Gradon
      L. (2006) Inhal Toxicol; 18: 773-780) demonstrated the applicability and
      relevance of considering realistic breathing patterns in analysis of aerosol flow
      and deposition within the human head airways. This issue is extended in the
      current paper, focused on a detailed analysis of spatial and temporal
      distribution of particle deposition in the oro-pharynx during inspiration. CFD
      modeling was used to determine both the 3D airflow structure and the local
      particle deposition fluxes at two different inspiratory patterns. Behavior of
      aerosol (particle size: 0.3-10 micro m, material density: 2200 kg m(-3)) was
      analyzed applying Lagrangian approach and considering Brownian effects for
      submicron particles. Results indicate that particles of different sizes are
      deposited in different parts of the oro-pharynx, depending on the point in the
      inspiration cycle. Larger particles (3-10 micro m) are separated efficiently in
      the naso-pharyngeal bend due to inertia, which predominate in the middle phase of
      inspiration. Submicron particles are deposited more uniformly in the oro
      pharyngeal space, and their separation from the air is enhanced in a short
      transition period between inspiration and expiration. It suggests the importance
      of mixing of inspired and expired air streams for particle deposition pattern.
      Comparison of our computational results of deposition to the approximation
      derived from the in vivo data (Stahlhofen W, Rudolf G, James AC. (1989) J Aerosol
      Med; 2: 285-308) shows a good agreement for particles, for which the inertia is a
      predominant mechanism of deposition. The results of this work lead to a more
      detailed description of the dynamics of oro-pharyngeal aerosol deposition during
      inspiratory part of the breathing cycle. The recognition of that problem is
      essential for prediction of toxic or pharmacological local effects of inhaled
      aerosols.

PMID- 17041243
TI  - Nanotechnology: the next big thing, or much ado about nothing?
AB  - Nanotechnology encompasses an increasingly sophisticated ability to manipulate
      matter at the nanoscale, resulting in new materials, products and devices that
      demonstrate new and unusual behaviour. While emerging nanotechnologies have great
      potential for good, there are increasing concerns that the selfsame attributes
      that make them attractive will also lead to new risks to human health. Research
      to date suggests that some purposely made nanomaterials will present hazards
      based on their structure--as well as their chemistry--thus challenging many
      conventional approaches to risk assessment and management. People involved in
      making and using these materials need to know what the risks are and how to
      manage them, if safe nanotechnology-based businesses are to emerge. Yet the
      challenges faced by the occupational hygiene community in ensuring safe nano
      workplaces are substantial. We currently know enough to suggest that some
      engineered nanomaterials will present new and unusual risks, but there is very
      little information on how these risks can be identified, assessed and controlled.
      And many nanomaterials are in production and use now. Good occupational hygiene
      practices and existing knowledge on working with hazardous substances provide a
      useful basis for working safely with nanomaterials. But where existing knowledge
      fails, new research is needed to fill the gaps: this must be strategically
      administered and targeted to addressing specific issues in a timely manner.
      Failing to take these steps will ultimately lead to people's health being
      endangered and emerging nanotechnologies floundering. However, with foresight,
      sound science and strategic research, we have the opportunity to ensure that
      emerging nanotechnologies are as safe as possible, while reaching their full
      potential.

PMID- 17041244
TI  - Comparison of the Grimm 1.108 and 1.109 portable aerosol spectrometer to the TSI
      3321 aerodynamic particle sizer for dry particles.
AB  - This study compared the response of two optical particle counters with that of an
      aerodynamic particle sizer. The optical particle counters rely on the amount of
      incident light scattered at 90 degrees by a particle to measure particle number
      concentration by optical particle size. Two models of optical particle counters
      from Grimm Technologies were used: the portable aerosol spectrometer (PAS) 1.108
      (0.3-20 microm in 15 channels); and the PAS 1.109 (0.2-20 microm in 30 size
      channels). With a substantially different operating principle from that employed
      by the optical particle counters, the aerodynamic particle sizer (APS) model 3321
      (TSI, Inc., St Paul, MN, USA) sizes particles according to their behavior in an
      accelerating flow to provide particle number concentration by aerodynamic size
      over a slightly narrower size range (0.5-20 microm) in 52 channels. The responses
      of these instruments were compared for three sizes of monodisperse solid aerosols
      composed of polystyrene latex spheres and a polydisperse aerosol composed of
      Arizona test dust. The PASs provided similar results to those from the APS.
      However, there were systematic differences among instruments in number and mass
      concentration measurement that depended upon particle size.

PMID- 17041245
TI  - Physical collection efficiency of filter materials for bacteria and viruses.
AB  - The purpose of this study was to determine the physical collection efficiency of
      commercially available filters for collecting airborne bacteria, viruses, and
      other particles in the 10-900 nm (nanometer) size range. Laboratory experiments
      with various polytetrafluoroethylene (PTFE), polycarbonate (PC) and gelatin
      filters in conjunction with Button Inhalable samplers and three-piece cassettes
      were undertaken. Both biological and non-biological test aerosols were used:
      Bacillus atrophaeus, MS2, polystyrene latex (PSL), and sodium chloride (NaCl).
      The B.atrophaeus endospores had an aerodynamic diameter of 900 nm, whereas MS2
      virion particles ranged from 10 to 80 nm. Monodisperse 350 nm PSL particles were
      used as this size was believed to have the lowest filtration efficiency. NaCl
      solution (1% weight by volume) was used to create a polydisperse aerosol in the
      10-600 nm range. The physical collection efficiency was determined by measuring
      particle concentrations size-selectively upstream and downstream of the filters.
      The PTFE and gelatin filters showed excellent collection efficiency (>93%) for
      all of the test particles. The PC filters showed lower collection efficiency for
      small particles especially <100 nm. Among the tested filters, the lowest
      collection efficiencies, 49 and 22%, were observed for 1 and 3-microm pore size
      PC filters at the particle sizes of 47 and 63 nm, respectively. The results
      indicate that the effect of filter material is more significant for the size
      range of single virions than for bacteria. The effect of filter loading was
      examined by exposing filters to mixtures of PSL particles, which aimed at
      mimicking typical indoor dust levels and size distributions. A 4-h loading did
      not cause significant change in the physical collection efficiency of the tested
      filters.

PMID- 17041246
TI  - Annals of Occupational Hygiene at volume 50: many achievements, a few mistakes,
      and an interesting future.
AB  - The past 10 years have seen a doubling of the number of papers submitted to the
      Annals, and a 5-fold increase in the number of institutions with access to the
      journal. Electronic access is now far more important than print access. Papers
      from British authors dominated the first 20 years of the journal, but the rest of
      Europe is now more important, with Scandinavia and The Netherlands being the
      major continental sources. North America is the other major source. For British
      papers, there has been a big growth in government authors, and a decline in
      papers from industry and armed forces. From many possible topics, trends are
      selectively reviewed in: standards and exposure limits; measurement methods and
      criteria; sampling strategy and statistics; fibres; control banding; dermal
      exposure; and evaluation of control. For the future, we will continue to have the
      same aims and standards, but the changes of the past few years, and the growth of
      new approaches such as open access, have emphasized the difficulty of
      forecasting. The growth in submissions from countries which we presently regard
      as 'developing', and especially the growth in higher education in China, and the
      amount of occupational disease there, are bound to have major impacts. Perhaps
      the English language will not continue to dominate scientific publishing, but in
      any case an eastward shift in the source of papers must lead to other changes.

PMID- 17041247
TI  - Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis.
AB  - It has recently been demonstrated that phosphatidylinositol 4,5-bisphosphate
      (PIP2) is localized at the cleavage furrow in dividing cells and its hydrolysis
      is required for complete cytokinesis, suggesting a pivotal role of PIP2 in
      cytokinesis. Here, we report that at least three mammalian isoforms of
      phosphoinositide-specific phospholipase C (PLC), PLCdelta1, PLCdelta3 and
      PLCbeta1, are localized to the cleavage furrow during cytokinesis. Targeting of
      the delta1 isoform to the furrow depends on the specific interaction between the
      PH domain and PIP2 in the plasma membrane. The necessity of active PLC in animal
      cell cytokinesis was confirmed using the specific inhibitors for PIP2 hydrolysis.
      These results support the model that activation of selected PLC isoforms at the
      cleavage furrow controls progression of cytokinesis through regulation of PIP2
      levels: induction of the cleavage furrow by a contractile ring consisting of
      actomyosin is regulated by PIP2-dependent actin-binding proteins and formation of
      specific lipid domains required for membrane separation is affected by
      alterations in the lipid composition of the furrow.

PMID- 17041248
TI  - Testing the theoretical framework of the COPE program for mothers of critically
      ill children: an integrative model of young children's post-hospital adjustment
      behaviors.
AB  - OBJECTIVE: To test a theoretical model examining processes through which a parent
      focused educational-behavioral intervention [Creating Opportunities for Parent
      Empowerment (COPE)] relates to children's post-hospital adjustment problems.
      METHODS: Mothers (n = 143) and their 2-7-year-old children, unexpectedly
      hospitalized in two pediatric intensive care units, were randomized to COPE or
      control conditions. Maternal measures included parental beliefs, anxiety,
      negative mood, and child adjustment 3 months post discharge. Observers rated
      maternal support of their children during hospitalization. RESULTS: Structural
      equation modeling suggested that the model tested provided a reasonable fit to
      the data [chi2 (97 df) = 129.43; p = .016; root mean square error of
      approximation = .048; comparative fit index = .95]. COPE effects on children's
      post-hospital externalizing behaviors were indirect, via associations with
      parental beliefs and maternal negative mood state. Furthermore, COPE
      participation was associated with more maternal support of their children, which
      was also associated with less internalizing and externalizing behaviors 3 months
      post discharge. CONCLUSION: Implementing COPE may help avert future mental health
      problems in this high risk population. Understanding the processes by which an
      already empirically validated program relates to child outcomes is likely to aid
      clinicians and administrators in the widespread uptake of the COPE program.

PMID- 17041249
TI  - The MDRD formula and validation.

PMID- 17041251
TI  - Genetic variability affects the development of brown adipocytes in white fat but
      not in interscapular brown fat.
AB  - Cold exposure induces brown adipocytes in retroperitoneal fat (RP) of adult A/J
      mice but not in C57BL/6J (B6) mice. In contrast, induction of the mitochondrial
      uncoupling protein 1 gene (Ucp1) in interscapular brown adipose tissue (iBAT)
      shows no strain dependence. We now show that unlike iBAT, in which Ucp1 was
      expressed in the fetus and continued throughout life, in RP, Ucp1 was transiently
      expressed between 10 and 30 days of age and then disappeared. Similar to the lack
      of genetic variation in the expression of Ucp1 in iBAT during cold induction of
      adult mice, no genetic variation in Ucp1 expression in iBAT was detected during
      development. In contrast, UCP1-positive multilocular adipocytes, together with
      corresponding increases in Ucp1 expression, appeared in RP at 10 days of age in
      A/J and B6 mice, but with much higher expression in A/J mice. At 20 days of age,
      brown adipocytes represent the major adipocyte present in RP of A/J mice. The
      disappearance of brown adipocytes by 30 days of age suggested that tissue
      remodeling occurred in RP. Genetic variability in Ucp1 expression could not be
      explained by variation in the expression of selective transcription factors and
      signaling molecules of adipogenesis. In summary, the existence of genetic
      variability between A/J and B6 mice during the development of brown adipocyte
      expression in RP, but not in iBAT, suggests that developmental mechanisms for the
      brown adipocyte differentiation program are different in these adipose tissues.

PMID- 17041252
TI  - Falls and patient safety for older adults.
AB  - The risk of falling increases with age. Falls in the elderly have been found to
      raise mortality and morbidity rates and are a leading cause of premature
      admission to long-term care facilities. Attention to known intrinsic and
      extrinsic factors that predispose to falling is important in community dwelling
      and institutionalized older adults. New government guidelines for long-term care
      facilities have helped focus attention on the safety aspect of fall risk and
      information about the physical and psychological impact of falling is increasing.
      Implementation of fall prevention protocols, including the use of fall risk
      assessment tools, may help reduce the incidence of falls and resultant
      complications.

PMID- 17041250
TI  - The natural inverse agonist agouti-related protein induces arrestin-mediated
      endocytosis of melanocortin-3 and -4 receptors.
AB  - Agouti-related protein (Agrp), one of the two naturally occurring inverse
      agonists known to inhibit G protein-coupled receptor activity, regulates energy
      expenditure by decreasing basal and blocking agonist-promoted melanocortin
      receptor (MCR) signaling. Here we report that, in addition to its inverse
      agonistic activities, Agrp exhibits agonistic properties on the endocytosis
      pathway of melanocortin receptors. Sustained exposure of human embryonic kidney
      293 cells to Agrp induced endocytosis of the MC3R or the MC4R. The extent and
      kinetics of Agrp-promoted MCR endocytosis were similar to the endocytosis induced
      by melanocortins. Using the bioluminescence resonance energy transfer technique,
      we further showed that after binding of Agrp both MCRs interacted with beta
      arrestins. In line with this observation, in COS-7 cells co-expression of beta
      arrestins enhanced Agrp-induced MCR endocytosis, whereas in human embryonic
      kidney 293 cells co-transfection of beta-arrestin-specific small interference
      RNAs diminished Agrp-promoted endocytosis. This new regulatory mechanism was
      likewise detectable in a cell line derived from murine hypothalamic neurons
      endogenously expressing MC4R, pointing to the physiological relevance of Agrp
      promoted receptor endocytosis. In conclusion, we demonstrated that Agrp does not
      solely act by directly blocking MCR signaling but also by reducing the amount of
      MCR molecules accessible to melanocortins at the cell surface. This beta-arrestin
      dependent mechanism reveals a new aspect of MCR signaling in particular and
      refines the concept of G protein-coupled receptor antagonism in general.

PMID- 17041253
TI  - Obesity: changing the face of geriatric care.
AB  - Statistics suggest that more and more older Americans are carrying extra weight
      an estimated 40% of individuals between the ages of 60 and 69 have a body mass
      index >30 and 30% of persons between ages of 70 and 79 years are obese. Obesity,
      coupled with the challenges of aging, leads to an unfortunate burden of chronic
      disease, functional decline, poor quality of life, and an increased risk of being
      homebound. Physical assessment of the elderly obese patient should include
      measurement of height, weight (to determine body mass index) and waist
      circumference (to address central obesity) and consideration of vascular, skin,
      and mobility issues. Weight management strategies such as diet and hydration
      should balance nutritional requirements with weight loss; particular attention to
      protein needs in chair- and bedbound patients is necessary. Additional approaches
      such as exercise, bariatric weight loss surgery, and weight loss medication
      should be considered on an individual basis related to their inherent risks in
      this population. Weight loss/management options framed from an interdisciplinary
      perspective can improve quality of life for these patients and their caregivers.
      Research specific to obesity in this age group is warranted.

PMID- 17041254
TI  - Lower extremity malignancies masquerading as ulcers.
AB  - Ulcers of the lower extremities, particularly in individuals >65 years old, are a
      common cause for visits to the podiatrist, wound care specialist, primary care
      physician, vascular surgeon, or dermatologist. When an ulcer does not respond to
      adequate medical and wound care, the potential for an underlying malignancy
      should be considered. Cutaneous malignancies that may masquerade as ulcers
      include nodulo-ulcerative basal cell carcinoma, squamous cell carcinoma,
      keratoacanthoma, nodular melanoma, tumor stage mycosis fungoides, lymphomatoid
      granulomatosis, lymphomatoid papulosis, angiosarcoma, and cutaneous metastases
      from internal malignancy. It is crucial for healthcare providers to recognize
      these presentations and render appropriate therapeutic intervention.

PMID- 17041255
TI  - Nutrition and aging: a transdisciplinary approach.
AB  - Numerous factors may predispose the elderly to decreased nutritional status.
      These include physical (illness, physiological changes related to aging, pain,
      and gastro-intestinal issues), psychological (depression), and socio-economic
      (income and decreased mobility that leads to isolation and loneliness). The
      latter may affect food insecurity and the ability to nourish and hydrate. When
      nutrition suffers, wellness and healing cannot be sustained. Healthcare providers
      should 1) be aware of the care implications associated with decreased nutritional
      status, 2) assess nutritional status, and 3) individualize treatment plans,
      providing and/or pursuing assistance for persons at risk for nutritional
      deficiency by interceding with commercially prepared products, medications, and
      supplements and securing consultations with dietitians. A transdisciplinary team
      approach (multidisciplinary across specialties and settings) can provide the
      needed care.

PMID- 17041256
TI  - Combinatorial protein design strategies using computational methods.
AB  - Computational methods continue to facilitate efforts in protein design. Most of
      this work has focused on searching sequence space to identify one or a few
      sequences compatible with a given structure and functionality. Probabilistic
      computational methods provide information regarding the range of amino acid
      variability permitted by desired functional and structural constraints. Such
      methods may be used to guide the construction of both individual sequences and
      combinatorial libraries of proteins.

PMID- 17041257
TI  - Global incorporation of unnatural amino acids in Escherichia coli.
AB  - The incorporation of amino acid analogs is becoming increasingly useful. Site
      specific incorporation of unnatural amino acids allows the application of
      chemical biology to protein-specific investigations and applications. However,
      the global incorporation of unnatural amino acids allows for tests of proteomic
      and genetic code hypotheses. For example, the adaptation of organisms to
      unnatural amino acids may lead to new genetic codes. To understand and quantify
      changes from such perturbations, an understanding is required of the
      microbiological and proteomic responses to the incorporation of unnatural amino
      acids. Here we describe protocols to characterize the effects of such proteome
      wide perturbations.

PMID- 17041258
TI  - Considerations in the design and optimization of coiled coil structures.
AB  - Coiled coil motifs are, despite their apparent simplicity, highly specific, and
      play a significant role in the understanding of tertiary structure and its
      formation. The most commonly observed of the coiled coils, the parallel dimeric,
      is yet to be fully characterized for this structural class in general.
      Nonetheless, strict rules have emerged for the necessity of specific types of
      amino acids at specific positions. In this chapter, we discuss this system in
      light of existing coiled coil structures and in applying rules to coiled coils
      that are to be designed or optimized. Understanding and expanding on these rules
      is crucial in using these motifs, which play key roles in virtually every
      cellular process, to act as drug-delivery agents by sequestering other proteins
      that are not behaving natively or that have been upregulated (for example, by
      binding to coiled coil domains implicated in oncogenesis). The roles of the a and
      d "hydrophobic" core positions and the e and g "electrostatic" edge positions in
      directing oligomerization and pairing specificity are discussed. Also discussed
      is the role of these positions in concert with the b, c, and f positions in
      maintaining alpha-helical propensity, helix solubility, and dimer stability.

PMID- 17041259
TI  - Calcium indicators based on calmodulin-fluorescent protein fusions.
AB  - Calmodulin (CaM) is an ubiquitous protein involved in Ca2+-mediated signal
      transduction. On Ca2+ influx, CaM acquires a strong affinity to various cellular
      proteins with one or more CaM recognition sequences, resulting in the onset or
      termination of Ca2+-regulated cascades. Through nuclear magnetic resonance and
      crystallographic structural studies of these Ca2+-CaM complexes, we have gained a
      deep understanding of CaM target recognition mechanisms. One immediate
      application is the creation of protein-based Ca2+ sensors using CaM complexes and
      green fluorescent proteins, previously named "chameleon." The major advantage of
      chameleons is that they can be expressed in single cells and targeted to the
      specific organelles or tissues to measure localized Ca2+ changes. This chapter
      describes the methods involved in cloning chameleons, characterizing their
      biochemical and biophysical properties, and imaging them in single cells using a
      digital fluorescence microscope.

PMID- 17041260
TI  - Design and synthesis of artificial zinc finger proteins.
AB  - Of the DNA-binding motifs, the (Cys)2(His)2-type zinc finger motif has great
      potential for manipulation. The zinc finger motif offers an attractive framework
      for the design of novel DNA-binding proteins. Specially, a structure-based design
      strategy is valuable for the creation of new artificial zinc finger proteins that
      have novel DNA-binding properties, namely, long-DNA recognition, DNA bending, and
      AT-rich sequence recognition. Herein, new strategies for the design of multi-zinc
      finger proteins for the recognition of a target DNA sequence, a DNA-bending zinc
      finger protein, a (His)4-type zinc finger protein, and an AT-recognizing zinc
      finger protein are described based on recent experimental results.

PMID- 17041261
TI  - Monobodies: antibody mimics based on the scaffold of the fibronectin type III
      domain.
AB  - We developed the use of the 10th fibronectin type III domain of human fibronectin
      (FNfn10) as a scaffold to display multiple surface loops for target binding. We
      termed FNfn10 variants with novel binding function "monobodies." FNfn10 is a
      small (94 residues) protein with a beta-sandwich structure similar to the
      immunoglobulin fold. It is highly stable without disulfide bonds or metal ions,
      and it can be expressed in the correctly folded form at a high level in bacteria.
      These desirable physical properties render the FNfn10 scaffold compatible with
      virtually any display technologies. This chapter describes methods for library
      construction and screening and for the production of monobodies.

PMID- 17041263
TI  - Protein library design and screening: working out the probabilities.
AB  - In designing protein libraries for selection, we must coordinate our capacity to
      create a large diversity of protein variants with the physical limitations of
      what we can actually screen. This chapter aims to bring the language of
      probabilities into the protein engineer's laboratory to answer some of our common
      questions: How can we most efficiently design a library? What fraction of the
      theoretical library diversity have we actually sampled at the end of the day?
      What is the probability of missing an individual of the library? Are the
      mutations present in the variants we have selected statistically meaningful or
      the product of random variation? The computation of these criteria throughout the
      process of experimental protein engineering will enable us to better design and
      evaluate the products of our libraries of protein variants.

PMID- 17041262
TI  - Engineering site-specific endonucleases.
AB  - Site-specific endonucleases are involved in many aspects of the biochemistry of
      nucleic acids. Restriction enzymes and their relatives have become paradigms for
      enzymes acting on DNA. Numerous efforts have been devoted to changing their
      specificity by rational protein design, with, by and large, little success,
      presumably because the recognition process is highly redundant and recognition
      and catalysis are tightly coupled. This chapter describes one of the few
      successful examples of a change in specificity--namely the conversion of the
      mismatch repair nuclease, MutH, which, when stimulated by MutS and MutL, nicks
      hemimethylated d(GATC) sites, into a variant that cleaves fully methylated DNA as
      well as hemimethylated and unmethylated DNA. This chapter will describe the
      various steps involved in this design project, starting from the analysis of the
      structure and the identification of candidate amino acid residues responsible for
      sensing the methylation status, to the generation and characterization of MutH
      variants with an altered specificity toward hemimethylated d(GATC) sites.

PMID- 17041264
TI  - Protein design by binary patterning of polar and nonpolar amino acids.
AB  - The design of large libraries of well-folded de novo proteins is a powerful
      approach toward the ultimate goal of producing proteins with novel structures and
      functions for use in industry or medicine. A method for library design that
      incorporates both rational design and combinatorial diversity relies on the
      "binary patterning" of polar and nonpolar amino acids. Binary patterning is based
      on the premise that the appropriate arrangement of polar and nonpolar residues
      can direct a polypeptide chain to fold into amphipathic elements of secondary
      structure that anneal together to form a desired tertiary structure. A designed
      binary pattern exploits the periodicities inherent in protein secondary
      structure, and allows the identity of the side chain at each polar and nonpolar
      position to be varied combinatorially. This chapter provides an overview of the
      considerations necessary to use binary patterning to design libraries of novel
      proteins.

PMID- 17041265
TI  - Versatile DNA fragmentation and directed evolution with nucleotide exchange and
      excision technology.
AB  - Mimicking natural evolution by DNA shuffling is a commonly used method for the
      optimization of DNA and protein properties. Here, we present an advancement of
      this approach whereby a gene library is amplified using a standard polymerase
      chain reaction (PCR), but incorporates dUTP as a fragmentation-defining exchange
      nucleotide, together with the four standard dNTPs. Incorporated uracil bases are
      excised using uracil-DNA-glycosylase, and the DNA backbone subsequently is
      cleaved with piperidine. This oligonucleotide pool is then reassembled with an
      internal primer extension procedure using a proofreading polymerase to increase
      yield, and, finally, is amplified by PCR. Denaturing polyacrylamide urea gels
      demonstrate this method to produce adjustable fragmentation size ranges dependent
      on the dUTP:dTTP ratios. Using the model protein, chloramphenicol
      acetyltransferase I, the sequencing of shuffled gene libraries based on a PCR
      containing 33% dUTP revealed a low mutation rate, of approx 0.1%, with an average
      parental fragments size of 86 bases, even without the use of a fragment-size
      separation. Nucleotide exchange and excision technology (NExT) DNA shuffling is,
      thus, reproducible and easily executed, making it superior to competing
      techniques. Additionally, NExT fragmentation outcome can be predicted using the
      computer software, NExTProg.

PMID- 17041266
TI  - Degenerate oligonucleotide gene shuffling.
AB  - Improvement of the biochemical characteristics of enzymes has been aided by
      misincorporation mutagenesis and DNA shuffling. Shuffling techniques can be used
      on a collection of mutants of the same gene, or related families of genes can be
      shuffled to produce mutants encoding chimeric gene products. One difficulty with
      current shuffling procedures is the predominance of unshuffled ("parental")
      molecules in the pool of mutants. We describe a procedure for gene shuffling
      using degenerate primers that allows control of the relative levels of
      recombination between the genes that are shuffled and reduces the regeneration of
      unshuffled parental genes. This procedure has the advantage of avoiding the use
      of endonucleases for gene fragmentation before shuffling and allows the use of
      random mutagenesis of selected segments of the gene as part of the procedure. We
      illustrate the use of the technique with a diverse family of beta-xylanase genes
      that possess widely different G and C contents.

PMID- 17041267
TI  - M13 bacteriophage coat proteins engineered for improved phage display.
AB  - This chapter describes a method for increasing levels of protein fusions
      displayed on the surfaces of M13 bacteriophage particles. By introducing
      mutations into the anchoring M13 coat protein, protein display levels can be
      increased by up to two orders of magnitude. Experimental methods are presented
      for the design, construction, and screening of phage-displayed libraries for
      improved protein display.

PMID- 17041268
TI  - Ribosome-inactivation display system.
AB  - We present a novel strategy for the connection of phenotype and genotype in vitro
      that can be used for the selection of functional proteins. The strategy involves
      the generation of a stable complex among a ribosome, an messenger RNA and its
      translated protein, without removal of the termination codon, as a result of the
      action of the ricin A chain during translation. The technique requires no
      transfection, no chemical synthesis, no ligation, and no removal of the
      termination codon. Thus, our novel ribosome-inactivation display system should
      provide, without loss of the pool population, a reliable, simple, and robust
      selection system for the in vitro evolution of the properties of proteins in a
      predictable direction by a combination of randomization and appropriate selection
      strategies.

PMID- 17041269
TI  - Compartmentalized self-replication: a novel method for the directed evolution of
      polymerases and other enzymes.
AB  - Compartmentalized self-replication (CSR) is a novel method for the directed
      evolution of enzymes and, in particular, polymerases. In its simplest form, CSR
      consists of a simple feedback loop involving a polymerase that replicates only
      its own encoding gene (self-replication). Self-replication occurs in discrete,
      spatially separate, noncommunicating compartments formed by a heat-stable water
      in-oil emulsion. Compartmentalization ensures the linkage of phenotype and
      genotype (i.e., it ensures that each polymerase replicates only its own encoding
      gene to the exclusion of those in the other compartments). As a result, adaptive
      gains by the polymerase directly (and proportionally) translate into genetic
      amplification of the encoding polymerase gene. CSR has proven to be a useful
      strategy for the directed evolution of polymerases directly from diverse
      repertoires of polymerase genes. In this chapter, we describe some of the CSR
      protocols used successfully to evolve variants of T. aquaticus Pol I (Taq)
      polymerase with novel and useful properties, such as increased thermostability or
      resistance to the potent inhibitor, heparin, from a repertoire of randomly
      mutated Taq polymerase genes.

PMID- 17041270
TI  - Synthesis of degenerated libraries of the ras-binding domain of raf and rapid
      selection of fast-folding and stable clones with the dihydrofolate reductase
      protein fragment complementation assay.
AB  - The protein-engineering field is mainly concerned with the design of novel enzyme
      activities or folds and with understanding the fundamental sequence determinants
      of protein folding and stability. Much effort has been put into the design of
      methods to generate and screen libraries of polypeptides. Screening for the
      ability of proteins to bind with high affinity and/or specificity is most often
      approached with phage display technologies. In this chapter, we present an
      alternative to phage display, performed totally in vivo, based on the
      dihydrofolate reductase (DHFR) protein-fragment complementation assay (PCA). We
      describe the application of the DHFR PCA to the selection of degenerated
      sequences of the ras-binding domain (RBD) of raf for correct folding and binding
      to ras. Our screening system allows for enrichment of the libraries for the best
      behaving sequences through iterative competition experiments, without the
      discrete library screening and expansion steps that are necessary in in vitro
      approaches. Moreover, the selected clones can be processed rapidly to
      purification by Ni-nitrilotriacetic acid (NTA) affinity chromatography in 96-well
      plates. Our methods are particularly suitable for the designing and screening of
      libraries aimed at studying sequence folding and binding determinants. Finally,
      it can be adapted for library-against-library screening, thus, allowing for
      coevolution of interacting proteins simultaneously.

PMID- 17041271
TI  - A general method of terminal truncation, evolution, and re-elongation to generate
      enzymes of enhanced stability.
AB  - Improving enzyme stability is a highly desirable design step in generating
      enzymes able to function under extreme conditions, such as elevated temperatures,
      while having the additional benefit of being less susceptible to cleavage by
      proteases. For these reasons, many different approaches and techniques have been
      devised in constructing such proteins, but the results to date have been of mixed
      success. Here, we present a robust method involving the terminal truncation,
      random mutagenesis and fragmentation, recombination, elongation, and finally,
      selection at physiological temperatures, to generate an enzyme with improved
      stability. Three cycles of directed evolution comprising of random mutagenesis,
      DNA shuffling, and selection at 37 degrees C were used, using the bacterial
      enzyme TEM-1 beta-lactamase as a model protein to yield deletion mutants with in
      vivo ampicillin resistance levels comparable to wild-type (wt) enzyme. Kinetic
      studies demonstrate the selected mutant to have a significantly improved
      thermostability relative to its wt counterpart. Elongation of this mutant to the
      full-length gene resulted in a beta-lactamase variant with dramatically increased
      thermostability. This technique was so fruitful that the evolved enzyme retained
      its maximum catalytic activity even 20 degrees C above its wt parent protein
      optimum. Thus, structural perturbation by terminal truncation and subsequent
      compensation by directed evolution at physiological temperatures is a fast,
      efficient, and highly effective way to improve the thermostability of proteins
      without the need for selecting at elevated temperatures.

PMID- 17041272
TI  - Iron deficiency in infancy and mother-child interaction at 5 years.
AB  - Five-year-old Costa Rican children, who had either chronic, severe iron
      deficiency or good iron status in infancy, were observed with their mothers
      during a structured interaction task in a laboratory setting and everyday
      interactions in their home. Child affect and behavior as well as the quality of
      mother-child interaction of the formerly chronic iron-deficient children (n = 40)
      were compared to those with good iron status in infancy (n = 102). Children who
      had chronic iron deficiency in infancy were more likely to display lower levels
      of physical activity, positive affect, and verbalization during the structured
      task at 5 years, despite iron therapy that corrected their iron deficiency anemia
      in infancy. Mother-child reciprocity during the structured task (e.g., eye
      contact, shared positive affect, turn taking) was more likely to be lower in the
      chronic iron deficiency group compared to the good iron group. Mothers of
      children in the chronic iron deficiency group showed less responsivity in both
      settings. These results show that children with chronic, severe iron deficiency
      in infancy continue at behavioral disadvantage relative to their peers at school
      entry. Sustained differences in mother-child interaction might contribute to the
      long-lasting behavioral and developmental alterations reported in children with
      chronic, severe iron deficiency in infancy.

PMID- 17041273
TI  - Characteristics of school-age children with autism.
AB  - The objectives of this study were to provide a national profile of children with
      autism, to describe the impact of autism on school functioning, and to describe
      the utilization of services among children with autism. We performed a cross
      sectional descriptive analysis of 9583 children (grades K-8) from the 2001
      National Household Education Survey Before and After School Survey. We used
      parent-reported information to determine the prevalence of autism, and children
      with autism were compared to children without autism on sociodemographic measures
      and several measures of school functioning and utilization of services. The
      prevalence of autism in this sample was 66 per 10,000. Children with autism were
      proportionately represented in all communities and all regions of the country.
      While children with autism were equally likely to attend public schools compared
      to children without autism, they were significantly more likely to have learning
      difficulties and to carry multiple diagnoses, including attention deficit
      disorder and learning disability. Most of these children received services for
      their disability through the school district. In conclusion, data from this
      survey yielded a prevalence estimate of autism similar to other recent studies.
      Children with autism have performance and behavior problems that persist despite
      the availability of services to the majority of children. The important needs of
      these children warrant further attention.

PMID- 17041275
TI  - Physical health of mothers with HIV/AIDS and the mental health of their children.
AB  - A longitudinal study was conducted on the psychological well-being of 81 young
      children (mean age = 8.8 years) living with mothers with AIDS or HIV-infected
      mothers with symptomatic disease. The relationship between mothers' physical
      health and children's psychological well-being was investigated. The children
      were assessed at seven time points over approximately 6 years. Individual growth
      models were estimated for children's depression, anxiety, and aggressiveness in
      relation to: mothers' viral load (medical records) and physical functioning,
      number of HIV-related physical symptoms, and medical visits due to illness (self
      report). Results showed significant linear declines in children's depression,
      anxiety, and aggressiveness over time. Lower levels of physical functioning and
      more physical symptoms among mothers were associated with higher levels of
      children's depression, anxiety, and aggressiveness at baseline. Lower levels of
      physical functioning and more physical symptoms among mothers were associated
      with initially high but more rapidly decreasing levels of depression among
      children. However, mothers who began the study in better health appear to have
      changed in health more quickly than mothers who began the study in poorer health.
      Thus, stability in mothers' health appears to be associated with a more rapid
      improvement in children's mental health over time. Our findings suggest that the
      measures representing observable levels of, and changes in, mothers' health that
      are most likely to be directly experienced by themselves and their children are
      the measures that are most predictive of changes in children's mental health over
      time.

PMID- 17041276
TI  - Predictors of stress in parents of children with fetal alcohol spectrum
      disorders.
AB  - This study examined child characteristics and family factors as predictors of
      stress in the biological or adoptive parents of 6- to 12-year-old children with
      fetal alcohol spectrum disorders (FASDs). Impaired executive functioning, poorer
      adaptive functioning, externalizing and internalizing behavior problems, and
      adoptive parent status all made significant and independent contributions to the
      prediction of higher levels of child domain stress, as reported by parents on the
      Parenting Stress Index. Biological parent status and fewer family resources were
      associated with higher levels of parent domain stress. Teacher ratings of the
      child"s executive functioning impairments and externalizing and internalizing
      behavior problems also were associated with parent reports of child domain
      stress. Findings highlight the need to provide support not only to children with
      FASDs, but to their caregivers as well.

PMID- 17041277
TI  - 11 Month-old twins with food avoidance.

PMID- 17041279
TI  - ADHD: new pharmacological treatments on the horizon.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder affecting school-age children. In many cases, symptoms
      persist into adolescence and adulthood, causing significant lifelong impairments
      in academic, career, and social functioning. The stimulants methylphenidate and
      amphetamines have been used for decades as first-line therapy for the treatment
      of ADHD. Short-acting stimulant formulations control symptoms only for a few
      hours, creating the need for multiple daily doses of the medication. For school
      age children, this necessitates administering medication during school hours,
      creating the potential for embarrassment and noncompliance. To offset these
      problems, longer acting stimulant formulations have been developed. Long-acting
      medications often control symptoms for up to 8 hours with only one daily dose of
      the medication, eliminating the need for in-school administration. Some long
      acting stimulants are designed to control symptoms for up to 10 to 12 hours.
      Although stimulants are effective in most cases, some children are unable to
      tolerate these medications. Nonstimulant options are available for the treatment
      of ADHD and include atomoxetine, alpha-adrenergic agents, and antidepressants. Of
      these, atomoxetine is the only medication approved to treat ADHD. In spite of the
      number of medications available for the management of ADHD, treatment options
      with greater flexibility and reduced side effects are still desirable. A
      transdermal methylphenidate patch has recently been approved, and advances to
      existing stimulants currently under development include an amphetamine prodrug
      and a longer acting formulation of amphetamine. In addition, a number of
      nonstimulant entities, including guanfacine and modafinil, are under development
      for the treatment of ADHD.

PMID- 17041282
TI  - Female monozygotic twins with selective mutism--a case report.

PMID- 17041283
TI  - Mental health and health-related quality of life: a 10-year follow-up of tortured
      refugees.
AB  - The aim of the study was to identify predictors of mental symptoms (posttraumatic
      stress disorder, depression, and anxiety), and of health-related quality of life
      in refugees 10 years after referral to the Rehabilitation and Research Centre for
      Torture Victims, and to study changes in mental health over time. The study
      sample comprises 139 tortured refugees admitted to a pretreatment assessment in
      1991 to 1994. Data on background and trauma, and in a subsample on mental
      symptoms, were collected at baseline. In 2002 and 2003, data on mental symptoms,
      health-related quality of life, and the participants' social situation were
      collected. The level of emotional distress was high at follow-up. Social
      relations and unemployment at follow-up were important predictors of mental
      health symptoms and low health-related quality of life. A significant decrease in
      mental symptoms was observed in the subsample. Social relations and unemployment
      should be taken into account when developing health-related and social
      interventions.

PMID- 17041284
TI  - Predicting medication-free treatment response in acute psychosis: cross
      validation from the Finnish Need-Adapted Project.
AB  - This study tested predictors of 2-year antipsychotic-free response from the
      Soteria study (older, better social functioning, fewer cardinal symptoms) using
      data from the Finnish Acute Psychosis Integrated treatment study. The quasi
      experimental study compared need-adapted family-oriented psychosocial
      intervention within a 3-week antipsychotic-free trial to psychosocial
      intervention plus antipsychotic medications. Forty-six percent of experimental
      completers (37% of intent-to-treat subjects) were successfully treated without
      antipsychotic medications for the entire 2-year study. The DSM-III-R diagnoses of
      schizophrenia and schizophreniform disorder and Soteria-suggested predictors were
      not related to antipsychotic-free response. Different variables within the same
      domains of good prognosis and fewer schizophrenia symptoms predicted
      antipsychotic-free response or nonresponse with 74% accuracy. The 6-month
      duration of symptom criterion distinguishing schizophrenia from schizophreniform
      disorder does not separate medication-free treatment responders from those
      requiring medications. Prognosis appears related to antipsychotic-free response
      and may be helpful in distinguishing schizophrenia from schizophreniform disorder
      in early episodes.

PMID- 17041285
TI  - Insight and recovery from acute psychotic episodes: the effects of cognitive
      behavior therapy and premature termination of treatment.
AB  - Research suggests that insight in schizophrenia is only weakly responsive to
      targeted psychosocial interventions. One of the aims of the present study was to
      examine the effects on insight of cognitive behavior therapy (CBT) for acutely
      psychotic patients. A second aim was to test predictions drawn from research on
      recovery styles that patients who reject psychological assistance will show a
      reduction in insight while those who continue to accept psychological assistance
      will show increases in insight over time. Patients with acute schizophrenia
      spectrum disorders were assigned at random to treatment-as-usual (TAU) or TAU
      plus CBT. The latter were also divided into those who terminated treatment
      prematurely (dropouts) and those who did not (stay-ins). Insight was assessed at
      baseline and three follow-up assessments. Insight increased over the follow-up
      period, but there were no differences between the CBT and TAU groups. Within the
      CBT group, dropouts showed a reduction in insight at the 6-month assessment
      before returning to their baseline level, while the stay-ins showed linear
      improvement up to 12 months. Possible explanations for these contrasting
      patterns, in terms of resilience, attachment styles, and an insecure sense of
      self, are discussed.

PMID- 17041286
TI  - Adherence to medication and quality of life in people with schizophrenia: results
      of a European multicenter study.
AB  - Quality of life is often severely impaired in people with schizophrenia, and
      adherence to antipsychotic medication has been consistently found to be low in
      this population. Although there is a considerable amount of evidence on these two
      variables in schizophrenia research, there is only limited knowledge on how they
      relate to one another. The aim of this study is to develop a meaningful model of
      the relationship between quality of life and adherence that includes mediating
      variables. A multicenter randomized controlled trial recruited 409 subjects in
      London, Verona, Amsterdam, and Leipzig. Baseline interviews obtained data on
      adherence, quality of life, and other variables. We used graphical modeling to
      investigate the relationships between the variables. No direct relation could be
      discerned between subjective quality of life and adherence to medication.
      Mediating variables, most importantly symptomatic impairment, global functioning,
      and medication side effects, were identified by the model. It can be concluded
      that, when aiming at the improvement of quality of life in people with
      schizophrenia, variables other than adherence, i.e., symptomatic impairment,
      global functioning, and medication side effects, should be targeted.

PMID- 17041287
TI  - Naive theory impairment in schizophrenia: is it domain-specific?
AB  - The ability to represent mental states of self and others to account for behavior
      is called theory of mind (ToM). This study examined whether ToM deficit in
      schizophrenia patients is a specific deficit in the cognitive component of
      interpersonal skills or a more global deficit, involving impaired information
      processing skills. Schizophrenia inpatients (N = 41) were compared with a control
      group of healthy subjects (N = 22) and to nonschizophrenia psychiatric patients
      (24 with affective disorders, seven with other psychosis) over a range of ToM
      tasks and another naive theory (theory of biology; ToB). Psychiatric inpatients
      as a whole showed significant deficit compared with the control group of healthy
      subjects in ToM tasks. The schizophrenia patients showed significantly larger
      deficits compared with patients suffering from affective disorder, while the
      performance of patients with nonschizophrenia psychosis was intermediate. In
      contrast, no difference was observed in the performance of the different groups
      on the ToB tasks. The fact that a deficit was found in ToM but not in ToB
      suggests a specific deficit in a cognitive component of interpersonal skills in
      schizophrenia rather than a general deficit in information processing skills.
      Naive theories deficits in schizophrenia seem to be domain-dependent.

PMID- 17041288
TI  - Jumping to conclusions and delusion proneness: the impact of emotionally salient
      stimuli.
AB  - The present study investigated whether those who are delusion-prone demonstrate a
      jumping to conclusions reasoning bias similar to that demonstrated by those with
      active delusions in previous studies. Two hundred individuals, none of whom had a
      psychotic disorder, were assessed for delusion-proneness and engaged in two
      probabilistic reasoning tasks, one emotionally neutral and the other emotionally
      salient. The emotionally salient task consisted of both positively and negatively
      valenced personally referent stimuli. Level of delusion-proneness was positively
      related to jumping to conclusions when stimuli were emotionally salient, though
      the bias was present only when the first personally referent stimulus was
      negatively valenced (p < 0.01). Thus, the jumping to conclusions reasoning bias
      previously demonstrated by individuals who have active delusions appears to be
      demonstrated under certain conditions by those who are not actively delusional
      but score high on a measure of delusion-proneness.

PMID- 17041289
TI  - Self-stigma in women with borderline personality disorder and women with social
      phobia.
AB  - Little is known about how women with borderline personality disorder (BPD) and
      women with social phobia react to mental illness stigma. The goal of this study
      was to assess empirically self-stigma and its correlates in these groups. Self
      stigma and related constructs were measured by self-report questionnaires among
      60 women with BPD and 30 women with social phobia. Self-stigma was inversely
      related to self-esteem, self-efficacy, and quality of life and predicted low self
      esteem after controlling for depression and shame-proneness. Stereotype awareness
      was not significantly correlated with self-esteem or quality of life. While there
      was no difference in stereotype awareness between women with BPD and women with
      social phobia, women with BPD showed higher self-stigma than women with social
      phobia. Self-stigma is associated with low self-esteem and other indices of poor
      psychological well-being. In comparison to women with social phobia, women with
      BPD suffer from more self-stigma. This may reflect intense labeling processes as
      being mentally ill due to repeated hospitalizations, frequent interpersonal
      difficulties, and visible scars.

PMID- 17041290
TI  - A valence-dependent group-specific recall bias of retrospective self-reports: a
      study of borderline personality disorder in everyday life.
AB  - Recall is an active reconstruction process likely to distort past experiences.
      This distortion, known as recall bias, seems to manifest itself differently in
      sick and healthy people. A recall bias has been documented in several disorders,
      but never investigated in borderline personality disorder (BPD). To determine
      recall bias in BPD, we assessed momentary and retrospective ratings of specific
      emotions in 50 patients with BPD and 50 healthy controls (HCs), using the
      methodology of 24-hour ambulatory monitoring. Our data reveal a group-specific
      valence-dependent recall bias of retrospective self-report, indicated by a
      different overall recall pattern in HCs and BPD. BPD patients show an overall
      negative recall pattern, whereas HCs show a positive recall pattern. A
      traditional questionnaire approach does not distinguish between symptoms of the
      disorder and recall bias, although the pathological mechanisms underlying them as
      well as the appropriate treatment strategies may be different.

PMID- 17041291
TI  - Specificity of patients' satisfaction with the delivery and outcome of treatment.
AB  - This study investigated the hypotheses that the general disposition to be
      satisfied is more influential than the nature of service delivery in determining
      satisfaction with treatment, and that there is a specificity to satisfaction with
      the delivery of care and with clinical outcome of care that makes their ratings
      distinct. Data were obtained by questionnaire at intake into treatment and 4
      months later from 154 male veterans. There were statistically significant
      relationships between the general disposition to be satisfied and satisfaction
      with treatment, but they had only a trivial effect on the relationships between
      treatment satisfaction and other variables. There was, however, a specificity to
      satisfaction ratings such that a major feature of the delivery of care, the
      experience of friendliness and caring from staff, was related more highly to
      satisfaction with care than to satisfaction with outcome, while measures of
      clinical outcome were related more highly to satisfaction with outcome than to
      satisfaction with care. A general disposition to be satisfied, therefore, appears
      not to have a major biasing effect on satisfaction with treatment. Further,
      patients appear to make valid differentiations between satisfaction with the
      delivery of care and the clinical outcome of care when their attention is focused
      specifically on satisfaction with these features.

PMID- 17041292
TI  - Diagnosing major depressive disorder VIII: are some symptoms better than others?
AB  - The present report from the Rhode Island Methods to Improve Diagnostic Assessment
      and Services project examined whether symptoms that are not part of the DSM-IV
      definition of major depressive disorder (MDD) are better at discriminating
      depressed from nondepressed patients than the current criteria. Symptoms assessed
      included diminished drive, helplessness, hopelessness, nonreactive mood, psychic
      anxiety, somatic anxiety, subjective anger, and overtly expressed anger. A total
      of 1538 psychiatric outpatients were administered a semistructured diagnostic
      interview. We inquired about all of the symptoms of depression for all patients.
      Diminished drive exhibited stronger performance in differentiating MDD from non
      MDD relative to all DSM-IV criteria except depressed mood, reduced
      interest/pleasure, and impaired concentration/indecisiveness. A compound
      criterion combining diminished drive with loss of energy was endorsed by nearly
      all MDD patients. Helplessness and hopelessness, when combined into a single
      criterion, performed more strongly than some of the DSM-IV criteria. Lack of
      reactivity, anxiety, and anger symptoms failed to differentiate more strongly
      than current DSM-IV criteria. The implications of these results for revising the
      diagnostic criteria for major depression are discussed.

PMID- 17041293
TI  - The relationship of premorbid functioning to illness course in schizophrenia and
      psychotic mood disorders during two years following first hospitalization.
AB  - Studies suggest that better premorbid functioning is associated with better
      outcomes in chronic schizophrenia. Yet first admission studies, which are more
      appropriate to examine this, are less conclusive. Also, little attention has been
      given to whether these findings hold for other psychoses. We examined the
      relationship of premorbid functioning using the Premorbid Adjustment Scale and
      outcomes in first admission psychoses (schizophrenia, N = 177; bipolar disorder,
      N = 106; major depression, N = 68) in the Suffolk County-wide mental health
      project. Poor premorbid functioning was associated with worse outcomes in all
      three diagnostic groups. Specifically, it was associated with more negative
      symptoms early in the course of illness, less improvement in negative symptoms,
      poorer overall clinical functioning, and poorer social functioning. Consistent
      with new epidemiological research, early assessment of premorbid functioning
      could provide an avenue for targeted interventions that might improve outcomes.

PMID- 17041294
TI  - Negative bias in the perception of others' facial emotional expressions in major
      depression: the role of depressive rumination.
AB  - Depressed individuals display a negative bias in the perception of others' facial
      emotional expressions. The extent of this selective processing, moreover, has
      proven predictive of a poor outcome in depression. However, to date, little is
      known about the possible mechanisms that may account for this bias. This study
      examined the hypothesis that rumination--an analytical type of self-focused
      attention--would be associated with higher levels of perception of negative
      facial emotions in major depression. Twenty-six depressed patients (17 women)
      completed the Perception of Facial Expressions Questionnaire, the Ruminative
      Response Scale, and other measures assessing depression-related constructs.
      Consistent with prediction, rumination was positively related to a negative bias
      in the judgment of facial expressions, even when controlling for other depression
      related variables. Although the correlational design of the present study limits
      the extent to which conclusions can be drawn on the directionality of the
      observed relationship, the present study reveals self-focused rumination as a
      possibly important causal mechanism in explaining depressed persons' negative
      bias in the perception of others' facial emotions.

PMID- 17041295
TI  - Risk factors for long-term posttraumatic stress reactions in unarmed UN military
      observers: a four-year follow-up study.
AB  - Follow-up data from 187 male Norwegian veteran officers from unarmed UN military
      observer missions were compared with follow-up data from 211 male veteran
      officers from Norwegian contingents of the UNIFIL peacekeeping mission in South
      Lebanon on stress exposure, posttraumatic stress symptoms, level of alcohol
      consumption, and problems with social adaptation after redeployment from the
      mission. Observer mission veterans reported exposure to significantly higher
      levels of war zone stressors than veterans from peacekeeping units did. Observer
      veterans also reported significantly more posttraumatic stress symptoms at follow
      up, higher alcohol consumption levels during service and at follow-up, and more
      problems with social adaptation to their lives at home in the years after their
      UN military service. All of these difficulties were most prominent in observers
      having served in missions with high-intensity stress exposure. Multivariate
      analyses demonstrated stress exposure during the mission and problems with social
      adaptation after homecoming to predict posttraumatic stress symptoms at follow
      up.

PMID- 17041296
TI  - Professional competencies for applied epidemiologists: a roadmap to a more
      effective epidemiologic workforce.

PMID- 17041298
TI  - A comprehensive Laboratory Services Survey of State Public Health Laboratories.
AB  - In November 2004, the Association of Public Health Laboratories (APHL) conducted
      a Comprehensive Laboratory Services Survey of State Public Health Laboratories
      (SPHLs) in order to establish the baseline data necessary for Healthy People 2010
      Objective 23-13. This objective aims to measure the increase in the proportion of
      health agencies that provide or assure access to comprehensive laboratory
      services to support essential public health services. This assessment addressed
      only SPHLs and served as a baseline to periodically evaluate the level of
      improvement in the provision of laboratory services over the decade ending 2010.
      The 2004 survey used selected questions that were identified as key indicators of
      provision of comprehensive laboratory services. The survey was developed in
      consultation with the Centers for Disease Control and Prevention National Center
      for Health Statistics, based on newly developed data sources. Forty-seven states
      and one territory responded to the survey. The survey was based on the 11 core
      functions of SPHLs as previously defined by APHL. The range of performance among
      individual laboratories for the 11 core functions (subobjectives) reflects the
      challenging issues that have confronted SPHLs in the first half of this decade.
      APHL is now working on a coordinated effort with other stakeholders to create
      seamless state and national systems for the provision of laboratory services in
      support of public health programs. These services are necessary to help face the
      threats raised by the specter of terrorism, emerging infections, and natural
      disasters.

PMID- 17041297
TI  - Fear of terrorism and preparedness in New York City 2 years after the attacks:
      implications for disaster planning and research.
AB  - OBJECTIVES: To help improve disaster planning and research, we studied
      psychosocial predictors of terrorism fear and preparedness among New York City
      residents after the World Trade Center disaster (WTCD). METHOD: We conducted a
      random cross-sectional survey of 1,681 adults interviewed 2 years after the WTCD.
      Participants were living in New York City at the time of the attack and exposed
      to ongoing terrorist threats. RESULTS: We found 44.9 percent (95% confidence
      interval [CI] = 41.9-47.9) of residents were concerned about future attacks and
      16.9 percent (95% CI = 14.7-19.3) reported a fear level of "10" on a 10-point
      analog scale. Furthermore, 14.8 percent (95% CI = 12.8-17.0) reported they had
      made some plans for a future attack, a significant increase from the previous
      year. In addition, although 42.6 percent (95% CI = 39.6-45.7) indicated that they
      would likely wait for evacuation instructions following a chemical, biological,
      or nuclear attack, 34.4 percent (95% CI = 31.5-37.3) reported they would evacuate
      immediately against official advice. Predictors of high terrorism fear in a
      multivariate model included Hispanic ethnicity (odds ratio [OR] = 2.0, P = .006),
      lower education (OR = 4.4, P < .001, and OR = 3.7, P < .001, respectively, for
      nonhigh school and high school graduates, compared with college graduates), being
      exposed to stressful life events (OR = 1.6, P = .048), having current
      posttraumatic stress disorder (3.1, P < .001), having a fear of death (OR = 2.5,
      P = .002), and reporting a likelihood of fleeing an attack against advice (OR =
      1.5, P = .034). The best predictors of preparedness in a multivariate model was
      being between 30 to 64 years old (30-44 years old, OR = 2.6, P = .001; 45-64
      years old, OR = 1.8, P = .03, respectively, compared with 18-29 years old),
      having higher exposure to the WTCD (moderate exposure, OR = 1.7, P = .05; high
      exposure, OR = 2.4, P = .002; very high exposure, OR = 4.1, P < .001),
      respectively, compared with no little WTCD exposure), and having greater exposure
      to other lifetime traumatic events (high traumatic event exposure, OR = 2.1, P =
      .005, compared with no exposure). CONCLUSION: Our study suggests that among those
      exposed to ongoing terrorism threats, terrorism fear and preparedness were
      related to socioeconomic factors, mental health status, terrorism exposure
      levels, and exposure to stressful life events.

PMID- 17041299
TI  - Local public health agency performance and community health status.
AB  - This study describes the results of an analysis of the relationship between local
      public health agency performance and health outcomes. Findings support the model
      that local public health agency performance affects community health status, and
      depending on the outcome, performance contributions vary. New hypotheses are
      offered that could help determine how system performance affects health outcomes.

PMID- 17041300
TI  - The Local Public Health System Assessment of MAPP/The National Public Health
      Performance Standards Local Tool: a community-based, public health practice and
      academic collaborative approach to implementation.
AB  - The Local Public Health System Assessment (LPHSA) in Mobilizing for Action
      through Planning and Partnerships (MAPP), and the Local Tool of the National
      Public Health Performance Standards Program (LT/NPHPSP)--which are one in the
      same-attempt to assess the capacity to provide the essential public health
      services. Both tools have been utilized in various public health practice
      settings; however, users have been challenged with the complexity of the tools
      and time and human resource investment necessary to complete them. The recent
      Journal of Public Health Management and Practice issue focus on MAPP provided
      several examples of LPHSA implementation, both as a component of MAPP and as a
      stand-alone activity in the context of performance standards. The uniqueness in
      our approach involved a collaborative between a community-based organization, a
      public health academic program, and a governmental public health agency which
      conducted the LPHSA in a manner that did not require actual modification of the
      tool itself, was practical and feasible, and was of benefit and value to all
      partners.

PMID- 17041301
TI  - Using principles of community-based participatory research to enhance health data
      skills among local public health community partners.
AB  - In a prior statewide health disparities assessment, local community public health
      and social service professionals indicated a need for technical capacity growth
      in order to understand and effectively utilize health data. Using a community
      based participatory research approach in addressing this need, health data
      training was provided to 26 individuals with the primary goals being to provide
      capacity to identify health disparities that result in higher morbidity and
      mortality, and to provide the skills needed to access, interpret, and utilize
      health data. Satisfaction surveys showed that an overwhelming majority of
      participants were extremely pleased with the training. Follow-up telephone
      interviews (100% response rate) conducted 2 months after the training indicated
      positive results, with participants discussing how they felt empowered to find,
      interpret, and use data as a result of the training. Results of a 6-month follow
      up questionnaire (54% response rate) further supported the program's desired
      outcome to expand participants' knowledge and use of health data. This pilot
      project illustrated how utilizing a community-level partnership approach to
      program development not only enhances the utilization of such programs but also
      helps sustain participants' knowledge and skills.

PMID- 17041302
TI  - Evaluation of the timeliness and completeness of a Web-based notifiable disease
      reporting system by a local health department.
AB  - OBJECTIVE: To evaluate the completeness and timeliness of the Colorado statewide
      Web-based system for reporting notifiable diseases, called the Colorado
      Electronic Disease Reporting System. This project demonstrates how a local health
      department can conduct a surveillance evaluation to identify areas of
      improvement. METHODS: Reports received by Colorado for 2004 were categorized as
      Tri-County Health Department (TCHD) reports and reports received for the rest of
      Colorado. Report completeness and timeliness were compared for all diseases
      routinely followed up by TCHD for both datasets. A data field was considered
      complete if there was data entry for that field. Timeliness in this study was
      defined as the interval between "specimen collection date" and "report date" for
      each record. RESULTS: Six of 12 selected data fields were 95% or more complete
      for both datasets. Twenty-four-hour notifiable diseases were reported a median of
      2.0 days for reports in the TCHD dataset and a median of 3.0 days for reports in
      the dataset for the rest of Colorado. Seven-day notifiable diseases were reported
      a median of 4.0 days for both datasets. CONCLUSIONS: Both Colorado datasets were
      found to be relatively complete and timely. Improved data collection by
      interviewers will help better determine demographic information of reported cases
      and timeliness of reports.

PMID- 17041303
TI  - Applying comprehensive community-based approaches in diabetes prevention:
      rationale, principles, and models.
AB  - The literature regarding the prevention of diabetes provides few standards for
      community-based initiatives. The present article offers four principles for
      engaging communities in comprehensive community approaches to diabetes prevention
      including (1) facilitating meaningful and central roles for communities, (2)
      giving primary attention to participatory processes rather than to best
      practices, (3) emphasizing cultural relevance in designing interventions
      particularly in racial and ethnic communities, and (4) incorporating social
      ecology approaches that are holistic and that address larger environmental
      influences rather than individual behavioral change alone. In order that
      community public health practitioners may operationalize the principles, models
      are provided for each.

PMID- 17041304
TI  - Low-fat milk and high-fiber bread availability in food stores in urban and rural
      communities.
AB  - As part of the Albany Prevention Research Center's Core Project to understand
      environmental influences on a healthy lifestyle, all food stores in downtown
      Albany (N=79) and rural Columbia and Greene counties (N=177) in New York State
      were visited and surveyed for their availability of low-fat milk and high-fiber
      bread. Stores in the rural community were significantly (P < .01) more likely to
      stock low-fat milk (71%) and high-fiber bread (55%) than stores in Albany (40%
      and 33%, respectively). The rural community also had a significantly higher
      population ratio of "healthy milk & bread (M&B) stores" (carrying both items)
      than Albany (7.6 vs 3.9 per 10,000 residents). Urban healthy M&B stores were more
      likely to be a convenience store and accept food stamps, whereas rural healthy
      M&B stores were more likely to be a gas station store and offer off-street
      parking. Multiple logistic regression analysis found that healthy M&B stores were
      inversely associated with proportions of ethnic/racial minorities in the census
      block group (CBG). More than 80 percent of minorities in Albany resided in a CBG
      without a healthy M&B store. Urban residents in predominantly minority
      neighborhoods were most likely to encounter environmental barriers to obtain
      healthy staple food, and intervention should be tailored to aid this population.

PMID- 17041305
TI  - Identifying housing that poisons: a critical step in eliminating childhood lead
      poisoning.
AB  - The purpose of our study was to develop a method to identify and prioritize "high
      risk" buildings in Chicago that could be targeted for childhood lead poisoning
      prevention activities. We defined "high-risk" buildings as those where multiple
      children younger than 6 years with elevated blood lead levels (BLLs) had lived
      and where lead hazards were previously identified on environmental inspection. By
      linking 1997-2003 Chicago elevated blood lead surveillance, environmental
      inspection, and building footprint data, we found that 49,362 children younger
      than 6 years with elevated BLLs lived at 30,742 buildings. Of those, 67 were
      "high-risk" buildings and these were associated with 994 children with elevated
      BLLs. On average, 15 children with elevated BLLs had lived in each building
      (range: 10-53, median: 13). Almost two thirds (n = 43) of the high-risk buildings
      had two or more referrals for inspection to the same apartment or housing unit;
      of those, 40 percent (n = 17) failed to maintain lead-safe status after
      compliance. Linking blood lead surveillance, environmental inspection, and
      building footprint databases allowed us to identify individual high-risk
      buildings. This approach prioritizes lead hazard control efforts and may help
      health, housing, and environmental agencies in targeting limited resources to
      increase lead-safe housing for children.

PMID- 17041306
TI  - Validity of self-reported health plan information in a population-based health
      survey.
AB  - OBJECTIVE: To validate information on private health insurance coverage in a
      population-based study. METHODS: Respondents to the Massachusetts Behavioral Risk
      Factor Surveillance System were asked the name of their health plan company
      (affiliation) and specific brand of insurance (product), the duration in which
      they belonged to the plan, and demographic and health-related data. Information
      on plan affiliation and product was used to classify individuals on type of
      coverage. At the end of the survey, respondents with health insurance were asked
      to retrieve their health plan cards, and to read detailed information from the
      cards. Self-reported data were compared with information from the cards. RESULTS:
      Self-reported information on health plan affiliation agreed with plan cards for
      93 percent of individuals, while agreement was 79 percent for health plan
      product. Among health maintenance organization (HMO) participants, 93 percent
      correctly reported being in an HMO (sensitivity), whereas 76 percent of
      respondents in a non-HMO plan correctly self-reported (specificity). Individuals
      with higher levels of income, those with a primary care doctor, and those in a
      health plan for at least 1 year had higher agreement. Higher validity was
      associated with poor physical health and recent cancer screening. CONCLUSIONS:
      Self-reported data on health plan affiliation and product have good validity in a
      population-based sample of adults. While agreement differs according to specific
      respondent characteristics, these differences do not appear substantial.

PMID- 17041308
TI  - The continued spread of HIV in the United States: prevention failure or systems
      defect?

PMID- 17041307
TI  - A comparison of breastfeeding rates in an urban birth cohort among women
      delivering infants at hospitals that employ and do not employ lactation
      consultants.
AB  - OBJECTIVE: To compare rates of breastfeeding at hospital discharge between
      facilities that employ and do not employ International Board Certified Lactation
      Consultants (IBCLCs). METHODS: This study used a cross-sectional design. Data
      from 11,525 birth certificates of Philadelphia residents who delivered in 2003
      were used. Breastfeeding was assessed using a question included on the
      Pennsylvania birth record, "Is the infant being breastfed at discharge?" The
      Philadelphia Department of Public Health's lactation consultants collected
      information on number of hours worked annually by IBCLCs by facility. RESULTS:
      After adjusting for race/ethnicity, education, insurance status, age, marital
      status, route of delivery, birth weight, and gestational age, delivering in a
      hospital that employed an IBCLC was associated with a 2.28 (95% confidence
      interval [CI] =1.98,2.62) times increase in the odds of breastfeeding at hospital
      discharge. Among women receiving Medicaid, delivering at a hospital that employed
      IBCLCs was associated with a 4.13 (95% CI =3.22,4.80) times increase in the odds
      of breastfeeding at hospital discharge. CONCLUSIONS: The findings presented here
      identify an association between delivering at a facility that employs IBCLCs and
      breastfeeding at hospital discharge. As the strength of this association is not
      negligible, particularly for women on Medicaid, these findings may be used to
      encourage widespread use of IBCLCs.

PMID- 17041309
TI  - The behavioral event interview: avoiding interviewing pitfalls when hiring.
AB  - The Management Moment" is a regular column within the Journal of Public Health
      Management and Practice. Edward L. Baker, MD, MPH, MSc, is serving as The
      Management Moment Editor. Dr Baker is Director of The North Carolina Institute
      for Public Health, School of Public Health, at the University of North Carolina
      at Chapel Hill. This column provides commentary and guidance on timely management
      issues commonly encountered in public health practice.

PMID- 17041310
TI  - Searching for lessons from the New Orleans Health Department: implications for
      public health practice.
AB  - The National Association footline of County and City Health Officials (NACCHO) is
      the national organization representing local health departments. NACCHO supports
      efforts that protect and improve the health of all people and all communities by
      promoting national policy, developing resources and programs, seeking health
      equity, and supporting effective local public health practice and systems.

PMID- 17041312
TI  - The global sex disparity in blindness and visual impairment.

PMID- 17041315
TI  - Central corneal epitheliopathy in a long-term, overnight orthokeratology lens
      wearer: a case report.
AB  - PURPOSE: The purpose of this study is to report an unusual case of central
      corneal epitheliopathy (CCE) in a long-term orthokeratology lens wearer. CASE
      REPORT: A single observational case report of a 12-year-old Chinese female myope
      with 3(1/2) years' experience in wearing orthokeratology lenses overnight was
      diagnosed with a CCE lesion during her regular orthokeratology aftercare
      consultation. The patient was asymptomatic. Trace or almost negative fluorescein
      staining was observed over the particular lesion area and, according to the
      clinical features of the corneal lesion, was thought to be a partially formed
      "dellen." The lesion healed after the use of the orthokeratology lenses was
      suspended for 4 months and reappeared when the patient resumed wearing the
      lenses. Close monitoring of the corneal condition was needed on this patient, and
      permanent discontinuation of the orthokeratology procedures will be considered if
      the signs and symptoms of the lesion worsen. DISCUSSION: The etiology, clinical
      management and the possible differential diagnosis of the central cornea "dellen"
      are discussed. CONCLUSION: A central corneal "dellen" may be associated with long
      term, overnight use of orthokeratology lenses.

PMID- 17041316
TI  - The morphology of the palpebral fissure in different directions of vertical gaze.
AB  - PURPOSE: The purpose of this study is to investigate the normative morphology of
      the palpebral fissure by measuring a range of biometric eye dimensions for a
      population of young subjects through analysis of digital images in primary gaze
      and two typical angles of downward vertical gaze. Palpebral fissure
      characteristics are clinically important in areas such as contact lens practice.
      METHODS: High-resolution digital images were taken of 76 young subjects with a
      range of refractive errors in primary gaze and 20 degrees and 40 degrees downward
      gaze. The digital images were analyzed to ascertain a range of biometric measures
      of the palpebral fissure for each subject in each angle of gaze. Repeated
      measures analysis of variance was used to investigate changes occurring in the
      palpebral fissure dimensions with vertical angle of gaze. RESULTS: Highly
      significant changes were found to occur in the horizontal and vertical palpebral
      fissure dimensions, the palpebral fissure angle, and the eyelid contour as a
      function of angle of gaze. The palpebral fissure narrows in the vertical
      dimension (from an average vertical palpebral aperture width for white subjects
      in primary gaze of 9.7+/-1.2 mm to an average width of 6.4+/-1.1 mm in 40 degrees
      downgaze), shortens in the horizontal dimension (from average horizontal
      palpebral aperture width of 27.1+/-1.5 mm in primary gaze to an average of 25.6+/
      1.8 mm in 40 degrees downgaze), and becomes more "down-slanted" with increasing
      downward gaze. CONCLUSIONS: Highly significant changes to the palpebral fissure
      dimensions occur in downward vertical gaze. These changes are important because
      many visual tasks are performed in downward gaze. These findings have
      implications for the management of lid anomalies and for contact lens fitting and
      design.

PMID- 17041317
TI  - Temporal progression and spatial repeatability of tear breakup.
AB  - PURPOSE: This study used image analysis to compare the temporal progression and
      spatial reoccurrence of the area of tear film breakup (AB) in dry eye and normal
      subjects. METHODS: Tear breakup was induced in 10 control and 10 dry eye subjects
      during the Staring Tear Breakup Dynamics (S-TBUD) test, which involves keeping
      one eye open for as long as possible, termed the maximum blink interval (MBI).
      Video imaging of tear film fluorescence measured the onset and progression of the
      AB. AB location and area were mapped. The progression of ABs from the first
      trial, the rate of tear breakup or dry area growth rate (DAGR), and the overlap
      of ABs in three successive trials 5 minutes apart were computed by custom MATLAB
      programs. RESULTS: The final AB before the blink was significantly greater
      (average, 30.7%+/-12.5% vs. 16.1%+/-9.2%) and the MBI was significantly less
      (average, 19.5+/-9.0 seconds vs. 56.5+/-38.9 seconds) among dry eye subjects
      compared with controls (p<0.05, Mann-Whitney U test). The DAGR was four times
      greater among dry eye subjects, who also showed significantly more tear breakup
      in the central cornea than controls (p<0.0001, Mann-Whitney U test). When the
      final image from three successive trials was overlapped, tear breakup occurred
      more often in the same location in three trials than would be expected by the
      overlap of independent points. CONCLUSIONS: Structural influences such as the
      "black line" or corneal lid defects appeared to influence the recurrence of
      breakup in the same region. The S-TBUD quantitative image analysis technique
      demonstrates that the tear film of subjects with dry eye continues to rapidly
      destabilize after an initial first break; thus, a low TBUT was combined with a
      high DAGR. The central corneal region of subjects with dry eye appeared
      especially susceptible to increased tear breakup when compared with controls.

PMID- 17041318
TI  - Tear meniscus height, lower punctum lacrimale, and the tear lipid layer in normal
      aging.
AB  - PURPOSE: The purposes of this study are to investigate the tear meniscus height
      (TMH), lipid layer, and critical dimensions of the lower punctum lacrimale (DPL)
      in normal human subjects over a large age range; and to determine the shape and
      general characteristics of the lower punctum lacrimale in a normal population.
      METHODS: TMH and DPL were measured using a graticule set at the eyepiece of a
      slit lamp biomicroscope (magnification 32x). Lipid layer was assessed by
      interferometry (Tearscope, Keeler). Only one eye (right) of each subject was
      assessed. All subjects were normals without any tear-related disorders and/or
      symptoms. RESULTS: Four hundred forty-four subjects were assessed (268 females,
      age range, 6-91 years; 176 males, age range, 6-91 years). Mean (+/-standard
      deviation) TMH in females was 0.19 mm (+/-0.11) and in males was 0.19 mm (+/
      0.10). TMH was related to age (x): in females, TMH=0.13+0.0009x (r=0.2393,
      p<0.001); in males, TMH=0.14+0.0008x (r=0.2492, p<0.001). TMH increased from 0.15
      mm (+/-0.06) in the young (<20 years) to 0.21 mm (+/-0.10) in the elderly (>80
      years). The punctum was closed in 10.8%, slit shaped in 24.3%, oval in 5.4%, and
      round in 59.5% of all cases. Mean age and TMH of those presenting with closed
      puncta was significantly higher than those presenting with open puncta (p<0.001).
      Mean (+/-standard deviation) area of open puncta was 0.008 mm (+/-0.013) in
      females and 0.010 mm (+/-0.018) in males. The difference was not significant.
      Diameter of round puncta was inversely related to age in females (r=-0.4985,
      n=149, p<0.001) but not within the males. A total of 14.6% of females and 12.5%
      of males presented with no discernible lipid layer. Lipid layer tended to be
      thinner in older subjects (one-way analysis of variance, F=6.667, p<0.001). There
      was no clear relationship between TMH and the lipid layer. CONCLUSIONS: There is
      a gradual increase in TMH and shift in size and shape of the punctum lacrimale
      with advancing years. Age-related changes in the lipid layer are expected to
      reduce tear volume by way of increased evaporation. On balance, it would appear
      any effects on tear volume by a thinning lipid layer are outweighed by changes in
      the puncta.

PMID- 17041319
TI  - Rigid gas-permeable contact lens base curve radius and transmissibility effects
      on corneal oxygen uptake.
AB  - PURPOSE: The purpose of this study is to determine the effects of rigid gas
      permeable contact lens thickness, base curve radius, and material permeability on
      corneal hypoxic stress. METHODS: Corneal oxygen uptake rates were measured with a
      Clark-type polarographic electrode on the right eye of 10 human subjects for the
      normal open eye (air) and after 5 minutes of static wear of rigid contact lenses
      of four cornea-to-contact lens base curve fitting relationships: 0.2 mm steeper
      than-K (STK), 0.1 mm STK, on K, and 0.1 mm flatter-than-K (FTK). There were also
      four materials (polymethylmethacrylate [Dk=0], lotifocon B [OP-2, Dk=15.9],
      lotifocon A [OP-3, Dk=30], lotifocon C [OP-6; Dk=60]) and three center
      thicknesses (0.14, 0.28, and 0.53 mm for the OP-6 lenses and 0.14 mm for all
      other materials) with all other parameters being constant. Each subject
      participated in two identical sessions. A repeated-measures analysis of variance
      was performed to compare the mean response across lens materials/thicknesses and
      the four curvature values. RESULTS: Significant differences were found only for
      lens material/thickness (p<0.0001). Although OP-2 and OP-6 (0.53 mm) were
      manufactured to have the same Dk/t, post hoc comparisons showed that the oxygen
      uptake rate with OP-6 (0.53 mm) was significantly lower. The same is also true
      for OP-3 and OP-6 (0.28 mm), with OP-6 (0.28 mm) having a significantly lower
      oxygen uptake rate. CONCLUSIONS: In contrast to past studies with PMMA, cornea-to
      contact lens base curve fitting relationship, with the lens materials and designs
      studied here, did not affect corneal hypoxic stress, and thick, high Dk lenses
      resulted in less change in corneal response than did thin, lower Dk lenses of the
      same Dk/t. This is attributed to the lens reservoir effect that has been
      previously described.

PMID- 17041320
TI  - Reduced corneal swelling and deswelling response in the iridocorneal endothelial
      syndrome.
AB  - PURPOSE: Despite severe abnormalities of the corneal endothelium in the
      iridocorneal endothelial (ICE) syndrome, the cornea can remain clear and maintain
      its normal thickness for years before corneal decompensation occurs. The aim of
      this study is to analyze this discrepancy by studying corneal hydration control
      in the ICE syndrome. METHODS: In four subjects with unilateral ICE syndrome,
      without signs of corneal decompensation, a "corneal stress test" was performed in
      both the affected and the unaffected eye. The stress test measures the recovery
      of corneal thickness after swelling induced by wearing a soft contact lens with
      the eyes closed. Corneal thickness was measured by noncontact pachymetry.
      RESULTS: Mean baseline corneal thickness of affected eyes (535+/-56 microm) was
      not different from unaffected eyes (526+/-39 microm). On the other hand, the
      corneal stress test showed a smaller induced swelling in affected eyes (33+/-15
      microm) compared with unaffected eyes (67+/-11 microm) and a slower recovery of
      corneal thickness in affected eyes. In one of four subjects, the cornea of the
      affected eye was calculated not yet to have recovered its original thickness
      before midnight. After this finding, although the cornea of this subject did not
      show any signs of clinical decompensation, the study was discontinued.
      CONCLUSIONS: Corneal hydration control is altered in the ICE syndrome. The ICE
      cornea can maintain its normal thickness despite severe morphologic abnormalities
      of the endothelium. Because we found that recovery of corneal thickness can be
      extremely slow, it cannot be guaranteed that such corneal "stress tests" are
      completely safe for subjects with the ICE syndrome, and we therefore feel that
      they should no longer be performed in these subjects.

PMID- 17041321
TI  - Deposition rates and lens care influence on galyfilcon A silicone hydrogel
      lenses.
AB  - PURPOSE: The purpose of this study is to investigate the frequency of deposition
      and impact of various multipurpose care regimens on a silicone hydrogel contact
      lens material (galyfilcon A; Acuvue Advance, Vistakon, Inc.). METHODS: This was a
      two-phase, monadic, open-label, daily-wear clinical study. The analyses from
      Phase I were aimed at determining total lens front surface area deposition after
      two 2-week periods of galyfilcon A lens wear. Deposition was graded clinically
      using a slit-lamp biomicroscope from grade 0 (0% surface area) to grade 4 (>25%
      surface area). Secondary outcomes included visual acuity and self-reported
      overall comfort, end-of-day comfort, and perceived vision. Phase II determined
      the impact of various multipurpose solutions with and without a rub step on
      "heavy depositors" (grade 3 or 4) from a single phase I site. There were four
      arms associated with phase II, and front surface deposition was again the primary
      outcome with the same secondary outcomes as that mentioned previously. RESULTS:
      In phase I, after the initial 2-week wear period, 9.4% of subjects exhibited
      grades 3 and 4 deposition. There were no differences in visual acuity, comfort,
      end-of-day comfort, and self-reported perceived vision when comparing
      "depositors" and "nondepositors." Twenty-seven "heavy depositors" from phase I
      completed phase II. After using Complete MoisturePlus (with a digital rub), no
      patients (0%) had clinically significant (grades 3 or 4) deposition, whereas for
      comparison, 33% of patients (the "heavy depositors") from phase I had clinically
      significant deposition without a digital rub (p=0.003). Similarly, 3.7% of
      patients had grade 3 or 4 deposition after using Opti-Free Express (with a
      digital rub) (p=0.01) and AOSEPT with a Miraflow-based rub (p=0.01) compared with
      the 33% of patients using Complete MoisturePlus without a digital rub. There were
      no differences in visual acuity or self-reported outcomes when stratified by lens
      care system in phase II. CONCLUSIONS: Less than 10% of subjects exhibit
      clinically significant levels of deposition with galyfilcon A lenses when cleaned
      with Complete MoisturePlus (no-rub) multipurpose solution, and this was shown to
      not interfere with lens performance. The addition of a rub-and-rinse step to the
      care of galyfilcon lenses significantly reduces this deposition rate.

PMID- 17041322
TI  - Objective and subjective responses in patients refitted to daily-wear silicone
      hydrogel contact lenses.
AB  - PURPOSE: Silicone hydrogel (SiH) lenses offer many physiological advantages for
      daily wear (DW) in addition to the continuous-wear modality for which they were
      originally developed. The purpose of this study was to investigate the clinical
      performance and physiological responses in a group of successful long-term
      wearers of conventional hydrogel lenses when refitted with DW SiH contact lenses.
      METHODS: Eighty-seven successful soft lens wearers (8.4+/-4.7 years of prior lens
      wear) participated in this study. Bulbar and limbal hyperemia were subjectively
      graded and digitally photographed for subsequent masked objective evaluation.
      Subjective symptoms were scored using visual analog scales. In addition,
      refractive error, corneal curvature, and corneal thickness were measured. All
      subjects were refitted with Focus Night & Day (lotrafilcon A) SiH lenses;
      however, to reduce the potential for bias, they were informed that they were
      being randomly assigned to wear either low oxygen permeability (Dk) lenses or
      high Dk SiH lenses and were "masked" as to their lens assignment. Subjects
      returned after 1 week, 1 month, and 2 months of DW, at which time all gradings,
      photographs, and measurements were repeated. End-of-day subjective symptoms were
      also graded periodically during the study. RESULTS: Ninety-three percent of
      subjects were successfully refitted. Both objective and subjective evaluations
      showed that bulbar and limbal hyperemia decreased significantly in all quadrants
      during the study (p<0.001), particularly for those subjects with greater baseline
      hyperemia (p<0.001). Subjects reported a concurrent reduction in end-of-day
      dryness and improved end-of-day comfort compared with their habitual lenses
      (p<0.001). No significant changes in refractive error, tarsal papillary response,
      corneal curvature, or corneal thickness were found during the study. CONCLUSIONS:
      Hyperemia in contact lens wearers may be attributed to a number of factors,
      including hypoxia. Refitting existing low Dk lens wearers with SiH lenses on a DW
      basis can result in a decrease in hyperemia, which may be significant for some
      subjects and also results in improvements in symptoms of dryness and discomfort.

PMID- 17041323
TI  - A comparison of wavefront aberrations in eyes wearing different types of soft
      contact lenses.
AB  - PURPOSE: The purpose of this study is to investigate the optical quality of eyes
      wearing different types of soft contact lenses (sCLs) using wavefront
      aberrometry. METHOD: A psychophysical aberrometer (WFA1000B; BriteEye, SuZhou,
      China) was used to measure wavefront aberrations for 56 eyes of 28 subjects under
      four conditions: 1) without contact lenses (non-CL), 2) with lathe-cut contact
      lenses (lathe-cut CL; Shuliang, Weicon Optics, Shanghai, China), 3) with cast
      molded contact lenses (cast-molded CL; Vistavue, J&J Vision Care, U.S.), and 4)
      with spun-cast contact lenses (spun-cast CL; Lanfenzhiji, Justcome Optics,
      Beijing, China). The three types of sCLs were made from different materials and
      lens design. The root mean square (RMS) values of the wavefront aberrations and
      individual Zernike aberrations were calculated and compared among the CL-wearing
      conditions. RESULTS: Astigmatism was not significantly changed by any of the
      three soft contact lenses when compared with the non-CL condition. However, a
      significant difference in the RMS values of higher-order aberrations was observed
      between the lens types (F=8.29, p<0.0001). Induced higher-order aberrations were
      found for both the cast-molded CL and the spun-cast CL conditions. There were
      significant differences in the aberrations in each of the higher orders between
      the CL conditions (F=3.77, p=0.011 for third order; F=5.31, p=0.002 for fourth
      order; F=13.86, p<0.0001 for fifth and higher orders). More higher-order Zernike
      aberrations such as coma and spherical aberration were induced by cast-molded CLs
      and/or the spun-cast CLs. CONCLUSION: Wavefront aberrations in the eyes with soft
      contact lenses vary from one individual lens type to another. Although the
      variation in wavefront aberrations could be attributed to the differences in the
      methods of manufacture, influences from other factors such as the lens material
      and lens design could not be excluded and deserve further investigation.

PMID- 17041324
TI  - History of mirrors dating back 8000 years.
AB  - PURPOSE: The purpose of this study is to consider the ancient history and early
      development of mirrors, because mirrors played a key role in refraction and
      magnification for an extended period of time before the invention of spectacles,
      including broad use in Roman times. FINDINGS: The earliest known manufactured
      mirrors (approximately 8000 years old) have been found in Anatolia (south central
      modern-day Turkey). These were made from obsidian (volcanic glass), had a convex
      surface and remarkably good optical quality. Mirrors from more recent periods
      have been found both in Egypt and Mesopotamia and still later in China and in the
      New World. In each of these areas, mirrors were in use by approximately 2000 BC
      or 4000 years ago.

PMID- 17041325
TI  - Another look at synovial fluid leukocytosis and infection.
AB  - Synovial fluid white blood cell counts are considered to be useful in diagnosing
      infectious arthritis, however, considerable overlap exists between infectious and
      noninfectious types of inflammatory arthritis. We undertook this review of
      synovial fluid studies at our institution to better define this degree of overlap
      and characterize the features of infectious arthritis in relationship to synovial
      fluid white cell counts. The records of 202 consecutive patients with synovial
      fluid white blood cell counts >2000/mm were reviewed. Infectious arthritis was
      diagnosed in 77% (10/13) of patients with counts >100,000, 47% (8/17) in the
      50,000-100,000 range, and 5% (9/172) with counts <50,000. Crystal-induced
      arthritis and rheumatoid arthritis made up 81% of patients in the 15,000-50,000
      range. Overall, 10 of 27 (37%) cases of infectious arthritis had white cell
      counts >100,000, and 18 of 27 (67%) had counts >50,000. A majority of these
      infections (14/18) were related to Staphylococcus aureus, while 5 of 7 infections
      associated with counts <20,000 were associated with atypical organisms. This
      study confirms that a majority of patients with very high synovial fluid white
      blood cell counts have infectious arthritis, and that the likelihood of infection
      is markedly reduced, but certainly not excluded, below this level. The presence
      of atypical infections in a small percentage of patients with low counts
      emphasizes the importance of clinical judgment in evaluating all patients with
      inflammatory arthritis, regardless of synovial fluid white cell counts.

PMID- 17041326
TI  - Fibromyalgia pain and substance P decrease and sleep improves after massage
      therapy.
AB  - Massage therapy has been observed to be helpful in some patients with
      fibromyalgia. This study was designed to examine the effects of massage therapy
      versus relaxation therapy on sleep, substance P, and pain in fibromyalgia
      patients. Twenty-four adult fibromyalgia patients were assigned randomly to a
      massage therapy or relaxation therapy group. They received 30-minute treatments
      twice weekly for 5 weeks. Both groups showed a decrease in anxiety and depressed
      mood immediately after the first and last therapy sessions. However, across the
      course of the study, only the massage therapy group reported an increase in the
      number of sleep hours and a decrease in their sleep movements. In addition,
      substance P levels decreased, and the patients' physicians assigned lower disease
      and pain ratings and rated fewer tender points in the massage therapy group.

PMID- 17041327
TI  - Cognitive and dissociative manifestations in fibromyalgia.
AB  - Memory decline and mental confusion frequently complicate the clinical
      presentation of fibromyalgia; however, formal cognitive examination often does
      not support deterioration. This paradox was examined in the context of
      dissociation, a condition with many cognitive similarities. Dissociation refers
      to the separation of parts of experience from the mainstream of consciousness. A
      common example is highway hypnosis. Eighty-nine fibromyalgia (FM) patients and 64
      other rheumatic disease patients were screened for memory decline and mental
      confusion using a questionnaire format. Pain, dissociation, affective distress,
      fatigue, sleep difficulty, and mental confusion were also assessed. Cognitive
      complaints (76.4%-43.8%) and dissociative symptoms (37.1%-1.9%) were
      overrepresented in patients with FM. Among FM patients with high dissociation,
      cognitive difficulties were reported by 95%; 100% of these cases reported that
      both memory and mental clarity were affected, a condition referred to as
      fibrofog. Dissociation in combination with fibrofog was associated with higher
      levels of FM symptom intensity and decreased mental well being. These findings
      suggest that dissociation may play a role in FM symptom amplification and may aid
      in comprehending the regularity of cognitive symptoms. Separating cases of
      fibrofog from cognitive conditions with actual brain damage is important. It may
      be prudent to add a test of dissociation as an adjunct to the evaluation of FM
      patients in cases of suspected fibrofog. Otherwise, test results may prove normal
      even in patients with disabling cognitive symptoms.

PMID- 17041328
TI  - Neutrophilic myositis: an extra-intestinal manifestation of ulcerative colitis.
AB  - Myositis of the skeletal muscle is rarely seen as an extraintestinal
      manifestation of inflammatory bowel disease. We report a case of a 36-year-old
      man with ulcerative colitis who developed 3 episodes of steroid responsive
      myositis in a 4-month period. He presented with a blistering rash followed by
      pain and massive swelling in the right shoulder and lower extremities, with
      marked elevation in muscle enzymes. Diagnosis of myositis was made after a muscle
      biopsy, which showed neutrophilic infiltrate in the deep subcutaneous tissue and
      skeletal muscle. Review of the literature indicates only a few cases of myositis
      associated with ulcerative colitis, most of them during an acute exacerbation of
      the disease. However, the present patient had his first episode when the
      ulcerative colitis was in remission. Myositis in ulcerative colitis may present
      atypically, in particular mimicking pyomyositis. Clinicians should be aware of
      this unusual steroid-sensitive complication.

PMID- 17041329
TI  - Pseudoxanthoma elasticum masquerading as Sjogren's syndrome.
AB  - Pseudoxanthoma elasticum is an inherited disorder of abnormal calcification of
      elastic fibers in the skin, retina, and cardiovascular system. Herein, we report
      a patient who had dry eyes and mouth, keratoconjunctivitis sicca, and a low titer
      ANA at presentation. A lip biopsy was performed to confirm a clinical suspicion
      of Sjogren's syndrome; however, the histologic findings were diagnostic of
      pseudoxanthoma elasticum. Antibodies to Ro and La were negative. Subsequently,
      she was found to have skin and eye findings consistent with pseudoxanthoma
      elasticum. Although a causal relationship between keratoconjunctivitis sicca and
      pseudoxanthoma elasticum is not proven, salivary gland involvement with
      pseudoxanthoma elasticum may explain this patient's symptoms. Physicians should
      consider the diagnosis of pseudoxanthoma elasticum in patients who present with
      sicca symptoms without obvious cause, especially if cutaneous or ophthalmologic
      abnormalities, or both, are present. Careful monitoring for associated problems
      is needed as soon as pseudoxanthoma elasticum is diagnosed.

PMID- 17041330
TI  - Isolated superior mesenteric artery vasculitis with response to glucocorticoids.
AB  - This report describes a patient with abdominal pain at presentation, which on
      angiography was found to be caused by vasculitis limited to the superior
      mesenteric artery. He was treated with oral glucocorticoids after an initial 5
      day course of pulse therapy and obtained excellent relief of symptoms. Steroids
      were tapered over 8 months. Repeat angiography revealed complete resolution of
      the vasculitis with a residual aneurysm of a branch of the left gastric artery,
      which was resected to avoid the risk of rupture. Histologic analysis revealed
      thickened intima with myxoid degeneration and no evidence of active vasculitis.
      Extensive laboratory and clinical investigations did not reveal an underlying
      connective tissue disorder to account for the gastrointestinal vasculitis. This
      report of an angiographically defined regional vasculitis involving the superior
      mesenteric artery with complete clinical as well as radiologic resolution on
      treatment with glucocorticoids alone emphasizes the need to differentiate between
      an isolated or regional vasculitis, which has an excellent prognosis, to avoid
      subjecting the patient to cytotoxic therapy with significant toxicities.

PMID- 17041331
TI  - Faces of eosinophilic fasciitis in childhood.
AB  - Eosinophilic fasciitis is a rare connective tissue disease in children
      characterized by hardening and thickening of the skin and soft tissues,
      peripheral eosinophilia, elevated erythrocyte sedimentation rate, and
      hypergammaglobulinemia. In this study, we report three pediatric patients with
      eosinophilic fasciitis whose clinical presentation and response to therapy
      differed from those reported in the literature. All three patients were female.
      Two of them had Raynaud's phenomenon as an initial feature, and the third had
      hepatosplenomegaly. Muscle involvement with weakness was present in two patients,
      as documented not only by increased aldolase levels at the time of presentation
      but also by inflammatory changes in the muscle biopsy. Serum immunoglobulin G
      levels were increased only in the most severely involved patient. Peripheral
      eosinophilia was present in all three cases. All three patients responded well to
      prednisone therapy. Two patients had a uni-phasic course, and one required
      further therapy to control a postinfection relapse. In summary, we found that
      Raynaud's phenomenon and hepatosplenomegaly can be part of the spectrum of
      clinical manifestations of childhood eosinophilic fasciitis. Identification as
      eosinophilic fasciitis and not scleroderma, despite hand involvement and
      Raynaud's phenomenon, can suggest that the illness may be steroid responsive.

PMID- 17041332
TI  - Color Doppler ultrasonographic findings show tendon sheath inflammation in
      mechanic's hands.
AB  - Two male patients with mechanics hands and concomitant interstitial lung disease,
      Raynaud's phenomenon, dermatomyositis-like rash, and arthritis were evaluated
      with gray-scale ultrasonography (US) and color Doppler US of the hands using a
      high-resolution hockey stick configuration 10-MHz transducer (ATL3000). Color
      Doppler US and gray scale US images of the flexor tendons were obtained at the
      level of the metacarpophalangeal joint. Initial gray-scale US demonstrated
      subcutaneous tissue and tendon thickening and synovial sheath effusion; color
      Doppler US demonstrated hyperemia of the subcutaneous tissues and tendons. Flexor
      tendon dysfunction on physical examination was proportional to hyperemia and
      thickening of structures shown by US. Follow-up examination, at a time when
      patients were improved, showed decreased blood flow in tendon sheaths and
      subcutaneous tissues and resolution of synovial sheath effusion; one patient,
      however, demonstrated accumulation within the sheath. Relative improvement in
      functional status mirrored the changes in the US. The color Doppler US finding of
      increased blood flow in the soft tissues of these two patients with mechanic's
      hands represents a physiologic anatomic abnormality amenable to treatment and
      provides prognostic information for these patients. Mechanic's hands and
      tenosynovitis occur in patients like these without muscle weakness.

PMID- 17041333
TI  - Spinal cord compression in atypical Wegener's granulomatosis.

PMID- 17041335
TI  - A surprise on joint fluid aspiration.

PMID- 17041334
TI  - Molecular biology and immunology for clinicians 17: T-cell signal transduction.
AB  - Peptide antigen recognition by T-cells occurs because of the interaction of the
      epitope cradled within the peptide-binding groove of the major histocompatibility
      complex molecule on the surface of an antigen-presenting cell with the T-cell
      antigen receptor, a heterodimer whose chains belong to the immunoglobulin
      superfamily. Passage of the message from the receptor to the cell's nucleus
      occurs via a complex choreography of kinases, calcium, and chemical combinations
      consisting of families of proteins described by arcane acronyms, numbers and
      letters that perplex the casual observer. However, taming the T-cell is crucial
      in transplantation and in controlling autoimmunity. Behind the jargon is a
      fascinating, albeit confusing, set of mechanisms that already offer therapeutic
      promise.

PMID- 17041337
TI  - Chronic arthropathy in childhood and sarcoid of skin and lungs in middle age. How
      are they related?

PMID- 17041338
TI  - Concurrence of relapsing polychondritis and psoriatic arthritis.

PMID- 17041339
TI  - Arthroscopic debridement and visco-supplementation: a minimally invasive
      treatment for symptomatic osteoarthritis involving the base of the thumb.
AB  - Symptomatic osteoarthritis of the base of the thumb is a common malady and is
      responsible for significant morbidity. This report describes a minimally invasive
      technique combining arthroscopic debridement and intraarticular visco
      supplementation in patients who do not respond to more conservative measures.
      Eleven patients with symptomatic osteoarthritis of the carpometacarpal joint not
      responding to antiinflammatory medications, injections, and splinting underwent
      arthroscopic debridement and intraarticular visco-supplementation. Using pain
      relief as a measure of success, 5 patients had excellent results, 4 patients had
      good results, and 2 patients had poor results. There were no complications. This
      procedure may provide a bridge between more conservative palliative therapies and
      the much more invasive open hand procedures currently being performed for this
      problem.

PMID- 17041340
TI  - Assessment of renal function in rheumatoid arthritis: validity of a new
      prediction method.
AB  - Medical treatment of patients with rheumatoid arthritis (RA) requires assessment
      of renal function. Because determination of endogenous creatinine clearance from
      a 24-hour urine collection is an unreliable and time-consuming procedure, several
      formulae that predict creatinine clearance from clinical and serum parameters
      have been developed. However, because of muscular atrophy, these formulae show
      lower correlations with measured creatinine clearance in patients with RA than in
      the healthy population. Recently, a new formula has been derived from the large
      Modification of Diet in Renal Disease (MDRD) study and has been shown reliably to
      predict renal function in individuals with renal dysfunction. To investigate the
      validity of this method in the RA population, estimates of creatinine clearance
      were derived using the most commonly used Cockcroft-Gault formula and the new
      MDRD method in control subjects and patients with RA. Age, height, serum albumin,
      blood urea nitrogen, and creatinine clearance were similar in both groups, but
      patients with RA had a lower body weight as well as serum and urinary creatinine
      concentrations. In control subjects, both methods showed comparable correlations
      with measured creatinine clearance (r = 0.82 and 0.83, respectively). In patients
      with RA, the Cockcroft-Gault formula revealed a lower correlation (r = 0.69) with
      a moderate bias (mean error = -10.7) and prediction accuracy (mean squared error
      = 342). For the MDRD method, r was still lower at 0.41, the mean error was -18.9,
      and the mean squared error was 479. We conclude that in patients with RA, the
      Cockroft-Gault formula is preferable to predict creatinine clearance before use
      of drugs such as methotrexate or nonsteroidal anti-inflammatory drugs.

PMID- 17041342
TI  - Definitely hip, but not trendy.
AB  - The etiology of hip discomfort and tendinitis often is confusing and the
      differential diagnosis is large. Some entities are overlooked because diagnosis
      requires appropriate clinical awareness and a specific radiographic examination.
      Coxa saltans, or snapping hip, is one of those commonly overlooked diagnoses.
      There are three types of snapping hip--the internal type, the external type, and
      the intra-articular type--and each presentation is unique. Most are symptomatic,
      but some may be quite painful and disabling. Evaluating the hip structures with
      bursography under dynamic conditions often is helpful to evaluate the anatomy and
      determine the etiology of the snapping hip. Treatment may range from conservative
      physical therapy, to corticosteroid injections, to arthroscopic treatment.

PMID- 17041343
TI  - Ciprofloxacin-related acute peripheral neuropathy in a patient with lupus
      nephritis.
AB  - Ciprofloxacin is a commonly prescribed antibiotic, and drug-related peripheral
      neuropathy is a rare side effect. A woman with lupus nephritis on high-dose
      prednisone presented with acute peripheral neuropathy within 2 days of starting
      ciprofloxacin for a urinary tract infection. Nerve conduction and
      electromyographic studies confirmed a predominantly sensory, bilateral, lower
      extremity neuropathy with mild motor nerve involvement. At initial presentation,
      it could not be determined whether neuropathy was secondary to lupus or related
      to ciprofloxacin. Based on the temporal association of drug initiation and the
      onset of neuropathy, ciprofloxacin was discontinued. Her symptoms resolved within
      2 weeks of ciprofloxacin discontinuation despite a simultaneous reduction in
      prednisone. The short duration of the peripheral neuropathy, the absence of lupus
      flare at the time of presentation, and the remission of symptoms during the
      prednisone taper all strongly suggest a rare but serious neuropathic adverse
      effect from ciprofloxacin. Ciprofloxacin neuropathy must be considered in
      patients with lupus who present with neuropathic symptoms after initiation of
      this commonly used antibiotic.

PMID- 17041344
TI  - Fungal arthritis of the knee caused by Candida parapsilosis in a kidney
      transplant recipient.
AB  - Fungal arthritis is a rare infection usually caused by Candida species. Candida
      parapsilosis has emerged as a new pathogen and has been implicated in several
      cases of fungal arthritis, mostly associated with a joint prosthesis or after
      arthrocentesis. We report an unusual case of fungal arthritis of the knee caused
      by this organism in a 38-year-old female kidney transplant recipient, who had no
      previous invasive procedures on her knee. Systemic and intraarticular antifungal
      therapy combined with surgical debridement proved to be an effective treatment of
      this clinically difficult condition. To our knowledge, this case is the first
      report of fungal arthritis caused by C. parapsilosis in a transplant recipient.
      The multimodality approach used in the treatment of this patient should be
      considered in similar forms of fungal arthritis in immunocompromised patients.

PMID- 17041345
TI  - Churg-Strauss syndrome and pregnancy: successful treatment with intravenous
      immunoglobulin.
AB  - Churg-Strauss syndrome is an extremely rare disease, and even less common in
      women of childbearing age. The initial management of Churg-Strauss syndrome
      consists of high doses of corticosteroids. Patients with severe disease, or those
      who are unresponsive to corticosteroids, usually are treated with cytotoxic
      drugs. Intravenous immunoglobulin (IVIg) has become a promising, but not
      completely accepted, form of treatment for systemic vasculitis that is
      unresponsive to standard therapy. We present a case of a woman diagnosed with
      Churg-Strauss syndrome that was refractory to corticosteroid and cyclophosphamide
      treatment. When she was found to be 3 months pregnant, treatment with IVIg was
      instituted with successful results. This case not only supports the beneficial
      effect of IVIg in Churg-Strauss syndrome, it illustrates its successful use in a
      patient who was pregnant.

PMID- 17041346
TI  - Catastrophic antiphospholipid syndrome: proposed guidelines for diagnosis and
      treatment.
AB  - The term "catastrophic" antiphospholipid syndrome (APS) was introduced to define
      an accelerated form of APS resulting in multi-organ failure. Although patients
      with the catastrophic form represent less than 1% of all patients with APS, they
      are usually in a life-threatening medical situation that requires high clinical
      awareness. In this article, we propose guidelines for the diagnosis and treatment
      of patients with catastrophic APS, based on the cumulated published experience of
      130 cases with this syndrome. We believe that it is essential that this syndrome
      should be diagnosed early and treated aggressively. The combination of high doses
      of heparin and corticosteroids plus intravenous gamma globulins or plasmapheresis
      is proposed as the treatment of choice in patients with this severe condition. In
      addition, preventive measures in patients with APS may be effective to avoid the
      development of catastrophic APS. We recommend that these proposed guidelines be
      tested in future prospective, collaborative studies to assess clearly the real
      prevalence and the best therapy for this life-threatening condition.

PMID- 17041347
TI  - The bone and joint decade 2000-;2010.

PMID- 17041348
TI  - Osteoporotic vertebral compression fracture causing neurologic deficit.
AB  - Osteoporotic vertebral fractures rarely cause neurologic deficits. We discuss a
      69-year-old man who presented with the signs of impaired function of the left L5
      nerve root. Imaging revealed a fracture of the posterior upper edge of the fifth
      lumbar vertebra with a bony fragment protruding into the spinal canal. The
      fracture was attributed to sneezing and coughing in this man with osteoporosis
      secondary to hypogonadism. Literature search revealed 64 cases of neurologic
      deficit associated with osteoporotic vertebral fracture. Most osteoporotic
      fractures with neurologic deficit (72%) occur at the thoracolumbar junction. The
      symptomatology of girdle-like pain and hypesthesia is not specific and may be
      misinterpreted as an abdominal problem or renal pain. A typical sign is the
      slowly progressive neurologic deficit, occurring spontaneously or after minor
      trauma such as a fall on the buttocks. Surgical treatment confirms the diagnosis
      and usually leads to remission of the neurologic signs. With increasing frequency
      of osteoporotic fractures in the developed world because of the expanding elderly
      population, cases with neurologic problems become more important.

PMID- 17041349
TI  - Molecular biology and immunology for clinicians 18: Heat shock
      proteins/chaperonins.
AB  - Heat shock proteins are a highly conserved set of families of proteins produced
      after a variety of stresses, both pathologic and physiologic. They are made by
      all living cells; all cells use basically the same mechanisms to deal with
      profound stresses. The second remarkable feature of the heat shock proteins is
      that their sequence and structure are remarkably conserved across broad stretches
      of evolutionary history: from Escherichia coli to Homo sapiens, heat shock
      proteins have not changed a lot! Finally, as alluded to previously, heat shock
      proteins are involved in physiologic functions as well, such as keeping hormonal
      and antigen receptors and cell cycle-related proteins in their appropriate state
      of readiness or inactivity, awaiting the ligand that will activate them.
      Polypeptide chains emerge from the ribosome as a straight chain that then assumes
      a tertiary structure (e.g., alpha helices, beta-pleated sheets, disulfide and
      hydrogen bonds). The process of folding into this final structure may require
      help because the required tertiary structure may not be the one into which the
      polypeptide chain would fold if left to its own devices. Scaffolding may be
      needed to coax the polypeptide to fold into its proper functional final
      structure, which may not be the morphology most thermodynamically favored. The
      polypeptide chain contains a series of potentially interactive surfaces (with
      other sections of the polypeptide or with other proteins in the cell), just as a
      receptor has at least one potentially interactive surface. Heat shock proteins
      guard these potentially interactive surfaces from unwanted interactions with
      extraneous and irrelevant "suitors" and may help coax the protein into the
      desired interaction. The alternative to this assistance may be that the protein
      folds into a useless blob or a shape that is not optimal for its intended use;
      such misfolded proteins are degraded by normal housekeeping functions of the
      cell. The highly conserved nature of heat shock proteins means that the immune
      response to heat shock proteins of pathogens or malignant cells may recognize and
      then react with host heat shock proteins and produce autoimmune disease.

PMID- 17041351
TI  - Ulcerating skin lesions and arthritis after a crab bite.

PMID- 17041353
TI  - Cutaneous vasculitis and antiphospholipid syndrome in a patient with ankylosing
      spondylitis: how may they be related?

PMID- 17041356
TI  - Question about coexisting lyme disease and parvovirus infection.

PMID- 17041354
TI  - Cerebrovascular disease in systemic lupus erythematosus (SLE): lack of
      association with anticardiolipin (aCL) antibodies.

PMID- 17041357
TI  - It's a dirty job but someone has to do it: thoughts about mud and other
      complementary and alternative therapies.

PMID- 17041358
TI  - Central nervous system compromise in primary Sjogren's syndrome.
AB  - Central nervous system (CNS) involvement in primary Sjogren's syndrome (SS) is
      poorly understood, and its frequency as well as its manifestations are subjects
      of controversy. The current study was undertaken to determine the prevalence and
      the clinical and immunogenetic characteristics of CNS compromise in a well
      defined group of patients with primary SS. In this retrospective study, patients
      fulfilled the European classification criteria. Among 120 patients with primary
      SS, 3 (2.5%) had CNS compromise (multiple sclerosis-like illness, complicated
      migraine, and optic neuritis with epilepsy). The CNS involvement coincided with
      the onset of sicca symptoms in 1 case. All 3 patients carried the human leukocyte
      antigen (HLA) DQB1*0303 allele and tested positive for anti-Ro antibodies, but
      not for anti-cardiolipin antibodies. Although rare, CNS compromise in primary SS
      can be the presenting manifestation of the disease in a few cases, and may be
      severe and varied.

PMID- 17041359
TI  - Therapy with mud compresses for knee osteoarthritis: comparison of natural mud
      preparations with mineral-depleted mud.
AB  - Mud pack therapy is an alternative mode of treatment for rheumatic diseases. It
      is based on the application of heated mud packs to the entire body or to specific
      areas, such as over joints. The aim of the current study was to evaluate the
      efficacy of treatment with mud compresses at patients' homes for osteoarthritis
      of the knee. Fifty-eight patients with osteoarthritis of the knee were enrolled
      in a prospective, double-blinded, controlled study. Forty patients were treated
      with natural mineral-rich mud compresses and 18 patients were treated with
      mineral-depleted mud compresses. Mud compresses were applied 5 times each week
      during 3 weeks for a total of 15 treatments. Patients were assessed at baseline,
      at completion of the 3-week treatment period, and twice after the conclusion of
      the treatment period-after 1 month and after 3 months. The main outcome measures
      were the Lequesne Index of severity of knee osteoarthritis, patient self
      assessment of pain, and severity of knee pain on a visual analog scale. A
      reduction of 20% or more in the pain scores was considered clinically
      significant. In the group treated with natural mud compresses, a significant
      reduction in knee pain was observed at all assessments. Similarly, improvement in
      the Lequesne Index was seen at the end of therapy and a month after treatment. In
      the control group, given mineral-depleted mud compresses, no significant change
      in knee pain was seen at any assessment. Improvement in the Lequesne Index was
      seen 1 and 3 months after completion of the therapy, but not at the end of
      therapy. Seventy-two percent of the patients in the treatment group had an
      improvement of >20% in self-assessment of knee pain, compared with 33% in the
      control group (p = 0.005). The data suggest that treatment with mud compresses,
      but only in their natural form, temporarily relieves pain in patients with
      osteoarthritis of the knees. We believe that treatment with mud compresses might
      augment conventional medical therapy in these patients.

PMID- 17041361
TI  - Transient elevation of the tumor markers CA 15-3 and CASA as markers of
      interstitial lung disease rather than underlying malignancy in dermatomyositis
      sine myositis.
AB  - A 37-year-old woman with severe interstitial lung disease associated with
      dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed
      organizing diffuse alveolar damage. Significantly elevated serum levels of the
      tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected,
      but no evidence of an underlying malignancy (including breast and ovarian) was
      found on serial clinical and radiologic examinations. These levels gradually
      normalized as the interstitial lung disease responded to a combination of
      cyclophosphamide and corticosteroids. The use of the CA 15-3 and CASA assays to
      measure serum levels of the highly glycosylated, high-molecular-weight mucin MUC1
      in interstitial lung disease has not been previously described. Clinicians should
      therefore be aware that elevation of these tumor markers may reflect the presence
      of interstitial lung disease rather than an underlying malignancy in patients
      with dermatomyositis, especially if the levels normalize after successful
      treatment of the lung disease.

PMID- 17041363
TI  - Sudden death in rheumatoid arthritis: pulmonary embolism--a fatal complication of
      iliopsoas bursitis.
AB  - Sudden death resulting from embolic complications of iliopsoas bursitis has not
      been previously reported. This case report deals with a 48-year-old woman with
      seropositive rheumatoid arthritis who presented with symptoms suggestive of deep
      vein thrombosis. She was found to have complete occlusion of the femoral vein
      secondary to iliopsoas bursal inflammation and swelling. She died suddenly. At
      autopsy, a large pulmonary embolism was identified as the cause of death. This
      report should increase awareness of the incidence of iliopsoas bursitis in
      rheumatoid arthritis and its potential danger. Early and aggressive management
      approaches described herein might have prevented this fatality.

PMID- 17041365
TI  - Paget's disease of bone in an Indian patient: genetic and environmental factors.
AB  - Epidemiologic data have shown that Paget's disease of bone is common among people
      of Anglo-Saxon descent, but it is believed to be rare in India and Asia. The
      worldwide prevalence of the disease shows pronounced geographic and ethnic
      heterogeneity, and can vary in populations through migration or loss of
      geographic isolation. The risk to an individual who changes geographic locations,
      however, is difficult to quantify because the specific genetic or environmental
      factors responsible for Paget's disease have yet to be completely determined. We
      describe a case of monostotic Paget's disease in a 59-year-old Asian Indian man,
      and consider the potential epidemiologic and etiologic influences (moving to an
      area of higher disease prevalence, role of genetics, viral exposures) that may
      have increased his risk for the disorder. The patient presented with several
      months of right anterior leg pain, and was found on examination to have anterior
      bowing of the tibia as well as warmth and an audible bruit. Radiographs of the
      tibia demonstrated a V-shaped lucency, enhanced trabecular pattern, and cortical
      thickening. Whole-body bone scan confirmed monostotic disease with expansile
      uptake in the tibia, and laboratory data revealed an elevated urinary collagen N
      telopeptide that normalized after bisphosphonate treatment, as did his clinical
      symptoms. In light of the environmental factors that appear significantly to
      influence the development of Paget's disease, the diagnosis should be considered
      in patients traditionally considered at low risk for the disorder.

PMID- 17041367
TI  - Fatal cytomegalovirus infection in two patients with systemic lupus erythematosus
      undergoing intensive immunosuppressive therapy: role for cytomegalovirus
      vigilance and prophylaxis?
AB  - Cytomegalovirus (CMV) infection is an uncommon but potentially fatal
      opportunistic infection in patients with systemic lupus erythematosus (SLE). We
      report 2 patients with severe SLE with life-threatening, multisystemic
      involvement who were treated with intensive immunosuppressive therapy. SLE was
      successfully controlled, but the patients succumbed to fatal reactivation of CMV
      disease despite antiviral therapy. Both were seropositive for CMV. We therefore
      advocate that there should be more active CMV vigilance, and polymerase chain
      reaction (PCR)-based CMV prophylaxis should be considered in CMV PCR-positive
      patients with SLE/rheumatic disease undergoing intensive immunosuppressive
      therapy.

PMID- 17041368
TI  - Upcoming international meetings.

PMID- 17041370
TI  - Molecular biology and immunology for clinicians 19: Protein purification and
      synthesis technology.
AB  - Everywhere one looks in the practice of medicine there is the need to understand
      things at the level of specific proteins: vaccine design using a single protein
      would be much safer and efficient than the whole organism; diagnostic tests would
      be less prone to false-positive results if a single protein could be used; and on
      and on. The DNA revolution allowed us to manipulate the specific genes making
      proteins of interest, leading to the ability to make single proteins, called
      recombinant proteins, in inexhaustible supply. And now we can make chimeric
      proteins, like the mythical animal, with the head of one protein, the tail of
      another, and perhaps the body of a third--as many components as you like, the sky
      is the limit.

PMID- 17041371
TI  - A case of multicentric reticulohistiocytosis initially misdiagnosed as lupus.

PMID- 17041369
TI  - Isolated digital gangrene complicating hepatitis a infection in a child.
AB  - Hepatitis A virus is rarely associated with extrahepatic complications. A child
      presented with a history suggesting Raynaud's phenomenon and severe digital
      gangrene, as a complication of hepatitis A infection. Coagulation study results
      (protein C, protein S, antithrombin III, and activated protein C resistance) were
      all normal except for anticardiolipin antibodies, which were present on initial
      presentation and resolved later. Antinuclear antibodies, rheumatoid factor, lupus
      anticoagulant, antineutrophilic cytoplasmic antibodies, and Venereal Disease
      Research Laboratory test were all negative. Cryoglobulins were not detected. C3
      and C4 levels were normal. Blood urea nitrogen and creatinine levels were normal
      as well. The patient was treated with aspirin and diclofenac, and improved slowly
      with complete resolution of gangrene and symptoms after 3 months. She remains
      asymptomatic 4 years later. Transient antiphospholipid syndrome or isolated
      Raynaud's phenomenon may be added to the list of extrahepatic complications of
      hepatitis A.

PMID- 17041372
TI  - Why are all these rows of joints involved?

PMID- 17041374
TI  - Combined antibiotic therapy of post-venereal reactive arthritis.

PMID- 17041375
TI  - Minimally-invasive salivary gland biopsy technique.

PMID- 17041376
TI  - Ethnic differences in male lupus.

PMID- 17041377
TI  - Are monoclonal gammopathies in rheumatoid arthritis predictive for
      lymphoproliferative disorders?
AB  - There is limited evidence for the association of specific malignancies with
      rheumatoid arthritis (RA). Monoclonal gammopathies can occur in RA. Their
      predictive value for the development of a lymphoproliferative disorder remains
      unclear and disputed. We reviewed charts of 214 RA patients all of whom had at
      least one serum protein electrophoresis. We performed a retrospective study of 12
      patients with RA and an M spike. We further characterized the M spike by serum
      immunofixation and bone marrow studies. The median age at which the M spike was
      identified was 69 years. IgG was the predominant gammopathy in 50% of patients,
      with no difference in the amount of kappa (kappa) and lambda (lambda) chains. One
      patient was diagnosed with multiple myeloma, one with an undefined primary
      lymphoproliferative disorder, one with T-cell leukemia, five with myelodysplastic
      syndrome, and four with monoclonal gammopathy of undetermined significance at
      most recent evaluation. Of our patients, 42% had a myelodysplastic syndrome,
      which has not been previously reported, and, in contrast to previous reports, no
      lymphomas were identified. The follow-up evaluation of patients with
      myelodysplastic syndrome and monoclonal gammopathy of undetermined significance
      is important because they may progress to an overt neoplasia.

PMID- 17041378
TI  - Cardiopulmonary exercise testing with pulmonary artery catheterization detects
      early pulmonary vasculature changes in patients with connective tissue diseases.
AB  - Pulmonary hypertension is a well-recognized complication of connective tissue
      diseases (CTD), with clinical symptoms typically limited to those with relatively
      advanced disease. The objective of this study was to identify patients with early
      pulmonary vasculature changes using cardiopulmonary exercise testing with
      pulmonary artery catheterization. Four patients with CTD and normal Doppler
      echocardiogram results identified as high risk for pulmonary hypertension on the
      basis of disease process underwent cardiopulmonary exercise testing with
      pulmonary artery catheterization. All patients had normal mean pulmonary artery
      pressures at rest (<25 mmHg), but exhibited an abnormal rise in mean pulmonary
      artery pressure with exercise. Cardiopulmonary exercise testing should be
      considered in patients at high risk for pulmonary hypertension to identify those
      individuals who may benefit from early therapeutic intervention.

PMID- 17041380
TI  - Antiprothrombin antibodies in patients with systemic lupus erythematosus or with
      primary antiphospholipid syndrome.
AB  - Some authors have found a strong statistical association of antibodies to
      prothrombin (aPT) with thrombosis in patients with antiphospholipid syndrome
      (APS); others have not confirmed this finding. It is unknown if the detection of
      aPT, in addition to anticardiolipin (aCL) and anti-beta2-glycoprotein-I (abeta2GP
      I) antibodies, provides additional information in the clinical study of these
      patients. We studied 38 patients with primary antiphospholipid syndrome and 466
      patients with systemic lupus erythematosus (SLE; 24 had a history of thrombosis
      and 69 had secondary APS). All were tested by ELISA for serum aPT (IgG and IgM)
      using irradiated and plain plates. We also detected aCL and anti-beta2GP-I by
      ELISA. One hundred sera from clinically healthy individuals were used as
      controls. Twenty-six percent and 11% primary APS sera were positive for IgG and
      IgM aPT, respectively, compared with 3% and 5% of controls (p < 0.001, both
      comparisons). We found no difference in the frequency of aPT in SLE patients and
      controls, but aPT were positive in 46% of lupus patients with a history of
      thrombosis (20% IgG, 33% IgM) and in 9% of those without thrombosis (6% IgG, 5%
      IgM; p < 0.001, both comparisons). Likewise, there was a significant difference
      in the frequency of aPT in SLE patients with (22%) or without (9%) secondary APS
      (p < 0.001). aPT titers decreased two- to sixfold when tested in plain plates.
      Thirty-five of 38 primary APS sera (92%) had IgG anti-beta2GP-I and 12 (31%) had
      aCL. No patient had aPT as the only antibody. The higher binding of aPT on
      irradiated plates suggests that aPT recognize a hidden epitope exposed by
      negative surfaces. The higher frequency of aPT found in patients with primary
      APS, SLE with thrombosis, or with secondary APS may suggest concerted pathogenic
      actions with other autoantibodies, but the detection of aPT does not seem to be
      of clinical value.

PMID- 17041381
TI  - Successful treatment of idiopathic febrile panniculitis (Weber-Christian disease)
      with thalidomide in a patient having failed multiple other medical therapies.
AB  - The authors describe a case of idiopathic nodular panniculitis (Weber-Christian
      disease) with recurrent febrile episodes resistant to glucocorticosteroids and
      methotrexate (MTX) in various combinations with hydroxychloroquine, azathioprine,
      cyclosporine, colchicine, and doxycycline. Thalidomide at 100 mg/day has induced
      a remission for 3 years.

PMID- 17041382
TI  - Pulmonary artery involvement in Takayasu's arteritis with lung infarction and
      pulmonary aspergillosis.
AB  - We describe a patient with a chronic case of pulmonary involvement of Takayasu's
      arteritis in the resected lung. A 49-year-old woman was first diagnosed with
      Takayasu's arteritis at age 30 years. On her first admission, she presented with
      Takayasu's arteritis and pneumonia with cavitation in the left lung. After
      recovering from pneumonia, she was treated initially with prednisolone, 30
      mg/day, and remained well until she developed hemoptysis at age 34 years.
      Findings suggesting aspergilloma were found in the same lobe on chest x-ray film
      when she was 46 years of age. By age 49 years, the hemoptysis became massive, and
      she was admitted for surgery. Left upper lobectomy and partial resection of S6
      and S8 pulmonary segments were performed. Histologic analysis of the resected
      lung revealed typical pathologic findings of pulmonary artery involvement in
      Takayasu's arteritis, such as stenosis recanalization and a vessel-in-vessel
      feature, but not active vasculitis. Infection probably occurred in the cavity of
      the infarcted tissue. Pulmonary artery involvement is common in Takayasu's
      arteritis, but the aspergilloma in this corticosteroid-treated patient is an
      uncommon complication.

PMID- 17041383
TI  - Mycobacterium marinum tenosynovitis in a patient on etanercept therapy for
      rheumatoid arthritis.
AB  - Opportunistic infections are a theoretical concern with the use of tumor necrosis
      factor antagonists, as these agents can impair host immunity. A 61-year-old man
      with rheumatoid arthritis being treated with only etanercept (soluble tumor
      necrosis factor receptor) and in remission from the rheumatoid arthritis
      presented with dorsal tenosynovitis of his right wrist. The synovitis was not
      improved by a local corticosteroid injection. Surgical exploration showed
      granulomatous inflammation, and cultures were positive for Mycobacterium marinum
      infection. Etanercept was discontinued 4 months after the hand infection started.
      The infection resolved completely with surgery and antibiotic therapy with
      clarithromycin 500 mg twice daily orally for 3 months. Although M. marinum
      infection was locally invasive, there was no systemic dissemination of the
      infection despite ongoing etanercept therapy for 4 months before it was
      discontinued. With more frequent use of this class of agents for rheumatoid
      arthritis and Crohn's disease, we caution physicians to be alert for the
      possibility of this kind of local opportunistic infection.

PMID- 17041384
TI  - Myasthenia gravis in a patient with pauciarticular juvenile chronic arthritis.
AB  - There have been reported cases of children with histories of pauciarticular
      juvenile chronic arthritis (JCA) later developing myasthenia gravis (MG) as young
      adults. This is intriguing because it had been considered rare to diagnose a
      second autoimmune disease in a patient with pauciarticular JCA, unlike in those
      with adult-onset rheumatoid arthritis. We report a case of MG in a 20-year-old
      woman with a history of pauciarticular JCA. She presented with bilateral ptosis,
      weakness, and a history of dysphagia. The diagnosis was confirmed with positive
      serum acetylcholine receptor antibodies (2000 nm/L) and electromyography showing
      a decremental response to repetitive muscle stimulation. The patient's
      inflammatory arthritis was quiescent at diagnosis. The patient underwent a
      surgical thymectomy and was treated with pyridostigmine, intravenous
      immunoglobulin, and corticosteroids with a fluctuating clinical course. Previous
      cases have been reported of MG associated with this subtype of JCA, suggesting a
      connection in autoimmune pathology. The earlier recognition and management of MG
      in a patient with pauciarticular JCA presenting with weakness may improve the
      prognosis of this disease.

PMID- 17041385
TI  - Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)
      associated with hypogammaglobulinemia and elevated serum tumor necrosis factor
      alpha levels.
AB  - Pyogenic aseptic arthritis, pyoderma gangrenosum, and cystic acne (PAPA) syndrome
      is an unusual triad that was recently mapped to a chromosome 15q mutation. We
      describe a patient from this kindred in whom hypogammaglobulinemia and elevated
      tumor necrosis factor-alpha serum levels were detected. The patient responded
      well to intravenous gammaglobulin and intra-articular corticosteroid therapy.
      Immune abnormalities can be found in PAPA syndrome and could be the consequence
      of the chromosomal abnormalities affecting candidate genes on this chromosome
      with subsequent abnormalities in cytokine or chemokine secretion. Rheumatologists
      should be alert for this syndrome. Correction of the immune abnormalities may be
      effective in controlling the disease manifestations.

PMID- 17041386
TI  - Thrombotic microangiopathy in a patient with adult onset Still's disease.
AB  - We report a case of a 23-year-old man with adult onset Still's disease (AOSD)
      developing a rare, life-threatening complication of thrombotic microangiopathy
      (TMA). While the AOSD was in an active phase, our patient first developed
      hemolytic uremia syndrome, soon followed by convulsions, sudden loss of vision,
      and thrombotic angiopathy of retinal vessels. After immediate and aggressive
      treatment with high dose prednisolone and 18 courses of plasmapheresis, he
      recovered from this severe complication. We think that the occurrence of TMA in
      AOSD may not be coincidental, although more reports are needed to support this.
      Early recognition and aggressive immunotherapy can allow patients with AOSD to
      completely recover from this life-threatening complication.

PMID- 17041389
TI  - An unusual synovial fluid as a clue to a cause of ankle monoarthritis.

PMID- 17041387
TI  - Molecular biology and immunology for clinicians 20: Angiogenesis and vascular
      growth factors and signals.
AB  - If we accept the perfectly reasonable premise that the mass of inflammatory
      tissue in rheumatoid arthritis (and psoriatic arthritis or any other inflammatory
      joint disease) requires oxygen and nutrition to survive and grow, we are
      confronted with a novel concept for therapy: if we can block the nutritional
      supply of the pannus, we can suppress or prevent its growth and the subsequent
      destruction of the joint. Thus, an understanding of how new blood vessels nourish
      the inflammatory mass could be pivotal in successfully treating our patients.
      Angiogenesis is the process whereby new blood vessels enter the site of
      inflammation or growing malignancy to supply the invading tissue. Many growth
      factors and local tissue conditions help to determine blood vessel growth, there
      being pro- and anti-angiogenetic influences. Thus, this is fertile ground for
      therapeutic molecular manipulations.

PMID- 17041391
TI  - Leflunomide in psoriatic polyarthritis.

PMID- 17041392
TI  - Implication of occult alveolar hemorrhage in Henoch-Schonlein purpura.

PMID- 17041394
TI  - Is coadministration of alendronate and nonsteroidal antiinflammatory drugs an
      unacceptable risk?

PMID- 17041395
TI  - Acute hip monoarthritis in systemic lupus erythematosus.

PMID- 17041396
TI  - Postmarketing surveys: up sides and down sides.

PMID- 17041397
TI  - Mini-aspirin: more facets of a tiny pill?

PMID- 17041398
TI  - Effect of minidose aspirin on renal function and renal uric acid handling in
      healthy young adults.
AB  - Minidose aspirin (60-325 mg/day) has been widely used in the prevention and
      treatment of cardiovascular and cerebrovascular diseases. However, studies on the
      effects of minidose aspirin on renal handling of uric acid and renal function are
      limited. We studied the effect of aspirin at 60 mg/day (n = 18) and 300 mg/day (n
      = 14) on uric acid handling and renal function in healthy subjects. The subjects
      were evaluated weekly during 2 weeks of aspirin therapy, and again 1 week after
      aspirin was discontinued. Aspirin at both dosages decreased the fractional
      excretion of uric acid. However, aspirin at 300 mg/day, but not 60 mg/day,
      significantly decreased uric acid clearance and creatinine clearance by the end
      of the second week of aspirin therapy. Despite these changes, serum uric acid and
      serum creatinine remained constant. The uric acid clearance, but not the
      creatinine clearance, returned to baseline value 1 week after aspirin therapy was
      discontinued. As aspirin at 60 mg/day showed no suppressive effect on renal
      function, it may be better for long-term use.

PMID- 17041399
TI  - Prescription and tolerability of meloxicam in day-to-day practice: postmarketing
      observational cohort study of 13,307 patients in Germany.
AB  - The goal of this study was to obtain data for prescription habits, tolerability
      for patients at high risk, and clinical effectiveness of meloxicam administered
      at 7.5 mg and 15 mg for various rheumatic diseases under real world prescribing
      conditions. This was a 3-month large-scale prospective observational cohort study
      in 4000 medical practices throughout Germany shortly after the introduction of
      meloxicam. To be eligible, patients had to have a diagnosis of acute or chronic
      active rheumatic disease for which nonsteroidal antiinflammatory drug (NSAID)
      therapy was required according to the prescribing information. In this study,
      13,307 patients receiving meloxicam prescriptions (7.5 mg in 65% and 15 mg in
      33%) were observed. The diagnoses of these patients included osteoarthritis
      (61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%), and other
      rheumatic conditions (28%). A substantial proportion of high risk patients were
      enrolled: 12% with a previous history of a perforation, ulceration, and bleeding
      (PUB), 24% with at least one concomitant cardiovascular disorder, and 26%
      receiving concomitant antihypertensive medication. Many of the patients (58%) had
      received NSAIDs before meloxicam, including patients with insufficient prior
      treatment effectiveness (43%) and those with NSAID-related adverse drug reactions
      (21%). In 85% and 94% of the patients, respectively, effectiveness and
      tolerability were rated as good or very good. Quality of life and daily functions
      improved in 64% to 84% of the patients. Only 0.8% of the patients reported
      gastrointestinal (GI) adverse drug reactions. Four uncomplicated cases of gastric
      ulceration, one serious perforated gastric ulcer, and one serious ileus
      complication were reported after incorrect use or overdosing of meloxicam.
      Treatment with the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam in
      doses of 7.5 mg and 15 mg resulted in meaningful treatment responses under real
      life conditions, despite inclusion of a substantial number of patients with
      insufficient effectiveness of previous use of non-COX-2 selective NSAIDs. All
      major GI toxicity (PUB) observed was owing to the fact that prescribing
      conditions were not respected appropriately. Despite a selection of high risk
      patients overall, GI, cardiovascular, and renal tolerability was favorable.

PMID- 17041400
TI  - Coronary electron beam computed tomography in 13 patients with systemic lupus
      erythematosus and two or more cardiovascular risk factors.
AB  - Cardiovascular and cerebrovascular events, the third leading cause of death in
      patients with systemic lupus erythematosus (SLE), are disproportionately common
      by age and gender. Risk factors for atherosclerotic cardiovascular disease
      (ASCVD) cannot reliably predict subsets of patients at risk for events. Coronary
      electron beam computed tomography (EBCT), a noninvasive imaging technique that
      quantifies ASCVD by measuring calcium deposition in the walls of coronary
      arteries, has been demonstrated to be a marker of ASCVD in traditional
      populations. A pilot group of 13 SLE patients (ages, 33-48 years) with two or
      more traditional risk factors for cardiovascular disease were studied by EBCT.
      Five of these SLE patients had calcification scores in the 70th percentile or
      higher, as compared with age-matched women without known coronary artery disease,
      and three had scores in the 90th percentile. Four of these five patients had
      antiphospholipid antibodies currently or in the past. These data suggest that
      EBCT may be able to detect premature ASCVD in SLE patients and may be a useful
      noninvasive tool as more attention is directed to ASCVD as a major complication
      of SLE.

PMID- 17041402
TI  - Coexistence of four autoimmune diseases in one patient: the kaleidoscope of
      autoimmunity.
AB  - Genetic, immune, hormonal, and environmental factors are associated with the
      multifactorial origin of autoimmunity. When one or more of these factors are
      altered, a "switch" from one autoimmune condition to another can occur,
      developing the so called "kaleidoscope phenomenon" of autoimmunity. We present
      the case of a 30-year-old woman with myasthenia gravis and hypothyroidism
      probably resulting from autoimmune thyroiditis. A thymectomy was performed, and 1
      year later, rheumatoid arthritis was diagnosed based on clinical, radiological,
      and serological features. Nine years after thymectomy, systemic lupus
      erythematosus was diagnosed based on skin, renal, hematologic, and immunologic
      manifestations. We suggest that the immune system function was modified when
      thymectomy was performed, playing an important role in the development of the new
      autoimmune conditions. Thymectomy increases the risk of developing a new
      autoimmune disease because it modifies, by mechanisms not well defined, the
      equilibrium and normal function of the immune system. This patient presents the
      infrequent association of four autoimmune conditions. When a patient has one
      autoimmune disease, she is at risk for another.

PMID- 17041403
TI  - Widespread cutaneous necrosis associated with antiphospholipid antibodies: report
      of four cases.
AB  - We describe four patients with widespread cutaneous necrosis as a manifestation
      of the antiphospholipid antibody syndrome. In three of the patients, the lesions
      were the first manifestation of the syndrome, and they were located in upper and
      lower extremities. Vascular thrombosis was present in the skin biopsy in all of
      the patients. Patients were effectively treated with anticoagulants, and healing
      occurred within 60 days. Such widespread cutaneous necrosis is a rare
      manifestation of the syndrome, and it must be regarded as major thrombotic event.
      Long-term treatment with anticoagulants must be considered. The recognition of
      these lesions is important, because they may be the onset of the syndrome,
      allowing its early diagnosis and treatment.

PMID- 17041404
TI  - Chorea and rapidly progressive subcortical dementia in antiphospholipid syndrome.
AB  - Antiphospholipid antibodies are associated with a variety of neurologic
      manifestations, both in patients with and without concomitant systemic lupus
      erythematosus. We report a patient in whom chorea and rapidly progressive
      subcortical dementia developed in the setting of persistently high titers of
      antiphospholipid antibodies. While some manifestations of antiphospholipid
      syndrome can be clearly linked to vascular thrombosis, it is not known whether
      this is also true for patients affected with chorea, dementia, or both. In our
      patient, serial magnetic resonance imaging showed the progressive development of
      deep white matter lesions but no cortical infarcts. The development of widespread
      pulmonary arterial thrombosis and acute cerebral ischemia, evidenced clinically
      and on diffusion-weighted magnetic resonance imaging of the brain, provided
      indirect evidence for a thrombotic pathogenesis for this patient's neurologic
      disease. Anticoagulation should be considered as an adjunct to the treatment of
      patients with antiphospholipid antibodies and chorea or subcortical dementia.

PMID- 17041405
TI  - Shrinking lung syndrome in systemic lupus erythematosus and Sjogren's syndrome.
AB  - Shrinking lung syndrome (SLS) is a rare complication of systemic lupus
      erythematosus (SLE) characterized by unexplained dyspnea, a restrictive pattern
      on pulmonary function tests, and an elevated hemidiaphragm. A total of 59 cases
      are reported in literature including the current case. The mean age of these
      patients is 36.85 years (range, 15-61 years), and the female-to-male ratio is
      6:1. This disorder is seen primarily during the later stages of SLE. The most
      common presenting features include dyspnea and pleuritic chest pain. Myositis has
      been reported in only 8 of 59 patients (13%). Diagnosis is made with chest x-ray
      showing an elevated hemidiaphragm and a restrictive pattern on pulmonary function
      testing without any evidence of interstitial lung disease along with decreased
      transdiaphragmatic pressure (Pdi). Corticosteroids are the most common method of
      treatment. Immunosuppressive therapy, beta-agonists, and theophylline are used in
      those resistant to steroids. The prognosis is generally good. This article
      reports the case of a 22-year-old man presenting with a 7-month history of dry
      mouth and dry eyes accompanied by increasing difficulty in breathing, progressing
      to dyspnea at rest. The patient's history included bilateral parotid gland
      swelling and nephrotic syndrome diagnosed 4 years earlier. Pertinent physical and
      laboratory findings included positive Schirmer's test results; bilateral parotid
      gland enlargement; bibasilar lung crackles; synovitis of the second and third
      proximal interphalangeal joints; a positive antinuclear antibody (Ro/SSA), Sm,
      and anticardiolipin antibodies; and elevated right hemidiaphragm on chest x-ray.
      Pulmonary function tests demonstrated restrictive lung disease with normal high
      resolution computerized axial tomography. A dramatic response to oral prednisone
      (60 mg daily) was observed in all of the patient's complaints in a matter of
      several days. A diagnosis of SLE with secondary Sjogren's syndrome (SS) and SLS
      was made. Although SLS has been reported in association with SLE, there has been
      only one previous report of SLS in SLE/SS overlap syndrome. Early recognition
      with appropriate treatment can decrease the morbidity associated with this rare
      syndrome.

PMID- 17041406
TI  - Intramuscular bleeding as a complication of anticoagulation treatment in a
      patient with systemic lupus erythematosus and antiphospholipid syndrome.
AB  - Thrombotic events account for significant morbidity and mortality among patients
      with antiphospholipid syndrome. The cornerstone of management includes long-term
      anticoagulation. However, the benefit of long-term anticoagulation must be
      weighed against the risk of bleeding complications. This article presents the
      case of a patient with systemic lupus erythematosus and antiphospholipid syndrome
      who experienced severe intramuscular hemorrhage as a complication of warfarin
      anticoagulation. This case emphasizes the importance of careful monitoring of
      anticoagulation treatment, and of recognizing a new differential diagnosis when
      dealing with a painful, swollen calf in the setting of lupus and antiphospholipid
      syndrome.

PMID- 17041407
TI  - Molecular biology and immunology for clinicians 21: The innate immune system: an
      introduction.
AB  - The human (mammalian) immune response includes two interrelated but separable
      components: the innate immune system and an adaptive immune response. The former
      constitutes the sole immune defense strategy of invertebrates. It is only with
      vertebrate evolution that an adaptive immune response, first cellular, then later
      humoral, develops. Recent studies and a reconsideration of the innate system
      allow a fuller appreciation of its complexities, unique qualities, and
      irreplaceable value. In the early days of an infection, long before an effective
      adaptive immune response can be mounted, the innate system puts up an effective
      defense. Innate systems provide the costimulatory signal needed to unleash the
      adaptive immune response. Future contributions to this series will provide
      details about some of the specific innate immune systems. This article serves as
      an introduction to this underappreciated (until recently) aspect of human immune
      defenses.

PMID- 17041410
TI  - Comment on bone mineral density and bone turnover markers in a group of male
      ankylosing spondylitis patients.

PMID- 17041411
TI  - Cholangiocarcinoma in a patient on long-term methotrexate: are there theoretical
      reasons for its occurrence?

PMID- 17041412
TI  - Clinical aspects of combined cyclosporin a and leflunomide therapy in rheumatoid
      arthritis.

PMID- 17041413
TI  - Small vessel vasculitis in Takayasu's arteritis.

PMID- 17041414
TI  - Fasciitis: what is the significance of various forms?

PMID- 17041415
TI  - The managed care versus fee for service dilemma and its impact on the outcome of
      lupus.

PMID- 17041416
TI  - Outcome of chilean patients with lupus nephritis and response to intravenous
      cyclophosphamide.
AB  - Several recent open studies suggest that the response rates of lupus nephritis to
      intravenous (IV) cyclophosphamide are lower than those observed in clinical
      trials. One explanation could be ethnic differences; for example, black patients
      more frequently have treatment-resistant lupus nephritis. Another could be the
      inclusion of patients who are noncompliant with therapy. From our register of 268
      systemic lupus erythematosus (SLE) patients examined between 1973 and 1996, 61
      patients were treated for proliferative lupus nephritis (17 had World Health
      Organization [WHO] type III and 43 had WHO type IV) and were followed through to
      2001. Exclusion criteria included a serum creatinine level >3 mg/dL. In this
      retrospective study, we assessed renal outcome and survival with an endpoint of
      end-stage renal disease (ESRD) or death (Kaplan-Meier). In the univariate
      analysis, worse prognostic factors for survival were serum creatinine >1.3 mg/dL
      (p < 0.001), age <30 years (p < 0.001), class 2 renal function stage (p < 0.03),
      and renal biopsy activity index >7 (p < 0.02). In the subgroup of 26 patients
      treated with IV cyclophosphamide, survival at 5 and 10 years was 82% and 73%,
      respectively. The dosage of IV cyclophosphamide was slightly lower than usual and
      used for a shorter period (median = 23 months) than what is usually recommended
      because of the high frequency of complications. Renal outcome of the IV
      cyclophosphamide-treated patients was poorer than that reported in the National
      Institutes of Health series (ESRD: 15% versus 3%). This low survival rate could
      reflect the short course and lower doses of IV cyclophosphamide used or ethnic
      differences. These data emphasize the need for continuous research for better
      tolerated drug schemes for treatment of our lupus nephritis patients.

PMID- 17041417
TI  - An overview of the use of computers in clinical rheumatology: models of care for
      the next millennium.
AB  - Practitioners of rheumatology in the 21st century are increasingly recognizing
      the benefits of computer technology as they relate to point-of-service care
      delivered in the hospital or in the outpatient setting. Electronic medical
      records and other computer-driven aids are resources emerging as affordable tools
      that can greatly enhance the rheumatologist's ability to provide stellar care,
      reduce professional and administrative burdens and improve lifestyle measures.
      Herein, we provide a practical nontechnical introduction to the world of
      electronic medical records, personal digital assistants, and other computer
      dependent tools, with an emphasis placed on how these instruments can be used by
      the clinical rheumatologist to achieve excellence in medical care.

PMID- 17041418
TI  - Impact of managed care on clinical outcome of systemic lupus erythematosus in
      Puerto Rico.
AB  - This study was designed to explore the impact of a managed care system on the
      morbidity and mortality rates in a systemic lupus erythematosus (SLE) cohort in
      Puerto Rico. The clinical manifestations and outcome measures of public SLE
      patients, before and after implementation of the managed care system, were
      compared with those of SLE patients treated in a private fee-for-service system.
      Of the cohort of 171 patients, 103 (60%) were treated in the public system and 68
      (40%) in the private sector. Except for higher prevalence of hematuria, renal
      insufficiency, and serositis in the public group, both groups had a similar
      prevalence of clinical manifestations, Systemic Lupus Erythematosus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage score,
      and mortality rate before introduction of the managed care system. Six years
      after implementation of the managed care system, medically indigent patients were
      more likely to have photosensitivity (90% vs. 75%), malar rash (85% vs. 65%),
      hematuria (43% vs. 24%), nephrotic syndrome (17% vs. 6%), and end-stage renal
      disease (8% vs. 0%). They also had a higher mortality rate (10% vs. 2%) and
      SLICC/ACR damage index score (1.5 vs. 0.8). In summary, SLE patients treated in
      the public system of Puerto Rico demonstrated higher morbidity and mortality
      after being treated in a managed care system compared with patients managed in a
      private fee-for-service system. Different from the fee-for-service system, the
      managed care system seeks medical care cost reductions that could affect the
      management and outcome of SLE patients. These differences could also be related
      to the higher disease severity before implementation of the managed care system
      and lower socioeconomic status of the public group. Nevertheless, the public
      managed care system in Puerto Rico requires continuous evaluation to ensure SLE
      patients better access to specialty and subspecialty healthcare and optimal
      pharmacologic treatments.

PMID- 17041419
TI  - Fasciitis after allogeneic peripheral blood stem cell transplantation in a
      patient with chronic myelogenous leukemia.
AB  - Fasciitis, one of the presentations of chronic skin graft-versus-host disease
      (GVHD), is characterized by symmetrical inflammatory swelling of extremities with
      or without eosinophilia, but it is rarely reported. This article describes a
      patient with the clinical and histologic features of fasciitis, as the only form
      of chronic GVHD that developed 20 months after HLA-matched allogeneic peripheral
      hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia
      (CML). She reported tightness of the skin and pain in both wrists and elbows on
      motion, with edema of the limbs. A deep cutaneous biopsy showed thickening of the
      subcutaneous fascia with inflammatory infiltrates. The patient was treated with
      cyclosporine and prednisone, which resulted in much improvement of her symptoms
      and signs related to the fasciitis. The authors recommend that clinicians
      maintain a high index of suspicion for fasciitis because fasciitis is a distinct
      entity among the chronic GVHD that may lead to a functional disability.

PMID- 17041420
TI  - Inflammatory arthritis associated with thromboangiitis obliterans.
AB  - Thromboangiitis obliterans (TAO) is an uncommon to rare vasculitis of small and
      medium arteries and veins typically affecting young male smokers. Inflammatory
      arthritis has only been rarely reported in association with TAO. We describe the
      case of a young male smoker presenting with inflammatory arthritis as the initial
      manifestation of his TAO. His arthritis resolved with a course of corticosteroid
      therapy. The vascular disease improved with hyperbaric oxygen therapy, although
      he continued to smoke. Similar cases have been described, suggesting that
      rheumatologists should keep Buerger's disease in mind in patients with arthritis
      and vascular disease.

PMID- 17041421
TI  - Blister as the initial presentation of gout.
AB  - We present a case of gout that presented initially as a bullous lesion. The
      patient had no history of gout, and the lesion was diagnosed initially as a
      simple pressure sore. Examination revealed a large blister over the right medial
      first metatarsophalangeal joint. Aspiration of the blister yielded cloudy fluid,
      with many monosodium urate crystals present on microscopic examination. There is
      scant literature on bullous lesions in gout. Such lesions can occur in patients
      known to have gout or can lead to the diagnosis of gout in previously undiagnosed
      patients. Gouty blisters likely form at sites of trauma, as has been proposed for
      gouty tophi. This case also emphasizes the importance of careful clinical and
      microscopic examination of aspirated fluid for crystals in the diagnosis of gout.

PMID- 17041422
TI  - Hypercapnic respiratory failure in systemic sclerosis.
AB  - Respiratory failure from causes exclusive of intrinsic lung disease is rare in
      systemic sclerosis. We report an unusual case of a young woman with diffuse
      systemic sclerosis who presented with proximal muscle weakness, dyspnea, weight
      loss, and nasal regurgitation. On physical examination, she had normal breath
      sounds but severe limitation of chest wall expansion. Pulmonary function tests
      (PFTs) were consistent with restrictive lung disease. Pulmonary pressures were
      normal on right heart catheterization and chest radiography and high-resolution
      computed tomography showed no evidence of intrinsic lung disease. Quadriceps
      muscle biopsy was consistent with type II atrophy, without any element of
      inflammatory myositis. After a meal, the patient aspirated, developed severe
      persistent hypercapnia, and required ventilatory support. Therapy with
      corticosteroids and intravenous gamma globulin failed to improve her condition,
      and the patient subsequently expired. Hypercapnic respiratory failure on the
      basis of chest wall involvement from systemic sclerosis may occur in the absence
      of intrinsic lung disease, and the prognosis, as in this case, may be grave.

PMID- 17041423
TI  - Systemic nocardiosis in a splenectomized patient with systemic lupus
      erythematosus: successful treatment using linezolid.
AB  - A splenectomized patient with systemic lupus erythematosus, who had previously
      been treated with high doses of corticosteroids, presented with headaches and
      symptoms of a respiratory tract infection. A magnetic resonance imaging scan of
      the brain revealed a ring-enhancing lesion, and Nocardia asteroides was isolated
      from a stereotactic biopsy specimen. After adverse reactions to a number of
      antibiotics, infection control was finally achieved by the new oxazolidinone
      drug, linezolid. Nocardiosis should be considered as a differential diagnosis in
      all immunocompromised patients who develop an obscure infection; delay in
      diagnosis and subsequent initiation of appropriate treatment often results in a
      fatal outcome. Linezolid is a new option for the treatment of nocardiosis and is
      effective when given orally.

PMID- 17041424
TI  - Fasciitis in amyopathic dermatomyositis.
AB  - Dermatomyositis is a disease frequently treated by rheumatologists and
      dermatologists due to prominent systemic features of inflammatory myositis, less
      common arthritis, and rare systemic vasculitis, in addition to the characteristic
      cutaneous manifestations of Gottron's papules over extensor surfaces, and a
      heliotrope rash over the eyelids. Patients with amyopathic dermatomyositis, a
      subset of dermatomyositis, display skin disease but no apparent muscle disease.
      This report describes an adult patient with the typical dermatomyositis rash with
      no weakness, normal muscle enzymes, and the unique finding of fasciitis without
      myositis on muscle biopsy, which correlated with a Magnetic Resonance Imaging
      (MRI) finding of a peripheral halo of intense signal around muscles on T2
      weighted and fat suppression sequences. Although MRI finding of presumed
      fasciitis has been reported in juvenile-onset dermatomyositis, this is the first
      report of MRI evidence of fasciitis with pathological correlation in adult-onset
      dermatomyositis. We suggest that if MRI scans are ordered, as part of the work-up
      of dermatomyositis, a peripheral halo of increased signal should specifically be
      looked for, which could be interpreted as fasciitis based on this case report.

PMID- 17041425
TI  - Iliac bone sarcoma presenting as hip pain.

PMID- 17041427
TI  - Does the joint fluid help?

PMID- 17041426
TI  - Molecular biology and immunology for clinicians 22: natural killer cell receptors
      and activation mechanisms.
AB  - Natural killer (NK) cells (called "third population cells" many years ago because
      they did not bear surface markers of the first two defined populations, B cells
      and T cells) are now known to occupy a pivotal position in the immune system,
      straddling the "divide" between the innate and adaptive responses. Natural killer
      cells are capable of production of many cytokines, both pro- and anti
      inflammatory, and induction of target cell death by lysis and/or programmed cell
      death (apoptosis). Some of these cytokines are pivotal in the autoimmune and
      antipathogenic immune responses, implicating NK cells in the pathogenesis of many
      human diseases. Multiple detection systems allow tight control of the potent
      effector systems that mediate NK cells' effects. Recent studies have shown that
      NK cell function is under tight control, with complex inhibitory and activating
      signaling assuring that these cells can accurately detect intracellular infection
      and malignant degeneration without damaging healthy cells. Although NK cell
      receptors do not have antigenic specificity, they do detect certain patterns on
      the surface of target cells. Their ability to make many cytokines that alter
      antigen-specific immune responses mediated by other cells puts NK cells in a
      unique position to influence both innate and adaptive responses.

PMID- 17041428
TI  - Patient satisfaction with COX-2 guidelines at a Veterans Administration hospital.

PMID- 17041429
TI  - Klinefelter syndrome with antisynthetase syndrome: why might they be associated?

PMID- 17041430
TI  - Cyclic post methotrexate dosing arthritis in systemic lupus erythematosus.

PMID- 17041431
TI  - Homocysteine and Behcet disease.

PMID- 17041432
TI  - Regional musculoskeletal examination: what the students say.
AB  - Confusion exists over which musculoskeletal examination skills medical students
      should learn. This study aimed to explore the views of third-year medical
      students. This was a qualitative study to allow in-depth exploration of beliefs
      and attitudes. Twenty students were randomly assigned to 1 of 2 focus groups.
      Their attitudes towards musculoskeletal examination were explored and discussed.
      The groups' discussions were recorded, transcribed, and framework analysis was
      undertaken with the aid of NUD*IST computer software. The following themes were
      identified: students dislike eponymous names for clinical tests; students felt
      there is a need for a more structured approach to musculoskeletal examination;
      students appeared unaware that many clinical tests were not based on evidence;
      students complained of a lack of confidence in the use of musculoskeletal
      clinical tests. Student's confidence in their musculoskeletal examination skills
      may be improved by the development of an agreed set of so-called core examination
      skills.

PMID- 17041433
TI  - Lupus pernio in sarcoidosis: clinical features and treatment outcomes of 14
      patients.
AB  - Lupus pernio (LP) is the most characteristic skin lesion of sarcoidosis. In this
      study, we retrospectively evaluated the clinical features of sarcoidosis patients
      with diagnosed LP at our center. Of 516 sarcoidosis patients diagnosed within a
      36-year period, 14 (2.7%) had skin lesions that were clinically and
      histologically diagnosed as LP. Thirteen of our LP patients were females, and one
      was a male (mean age: 46.3, range: 24-67). In 2 sarcoidosis patients, the initial
      presentation of the disease was LP. When the LP patients were compared with other
      sarcoidosis patients, there were more females, and the frequency of
      extrapulmonary involvement and the number of patients with advanced stage disease
      were higher (P <0.001). Oral and/or intralesional steroid therapy was the
      preferred treatment modality in all our patients and led to either recovery or
      regression in most patients with LP. As our study was an uncontrolled,
      retrospective one with few patients, it is difficult to say whether steroids are
      effective. LP runs a chronic course and spontaneous remission of lesions of more
      than 2 years' duration is quite rare. Because of the unwanted side effects of
      steroids, the efficacy of new treatment modalities should be tested especially in
      sarcoidosis patients with only skin involvement.

PMID- 17041434
TI  - Evidence for disseminated Mycoplasma fermentans in New Jersey residents with
      antecedent tick attachment and subsequent musculoskeletal symptoms.
AB  - Mycoplasma species are one of nature's most abundant groups of microbes. These
      bacteria inhabit a wide diversity of insect, plant, and animal species, including
      humans. Certain mycoplasma species have been identified in blood-sucking
      arthropods, including Ixodes ticks. Frequent human exposure to this genus of
      ticks led us to explore the possibility of tick-mediated transmission of these
      bacteria. We evaluated 7 residents of central New Jersey who developed fatigue,
      musculoskeletal symptoms, and cognitive disturbance after tick attachment. All 7
      of these patients lacked both serological evidence and erythema migrans skin
      lesions characteristic of Lyme disease. We were able to amplify and quantitate
      Mycoplasma fermentans-specific DNA from their peripheral blood lymphocytes. After
      antimicrobial therapy, symptoms subsided, and M. fermentans DNA could no longer
      be detected in their blood specimens. These findings suggest that a subset of
      disseminated M. fermentans infections may be a vector-mediated process in humans
      and should be considered in patients with puzzling musculoskeletal presentations.

PMID- 17041435
TI  - Historical vignette: Raynaud's phenomenon as perceived by musculoskeletal
      specialists (1862-1957).

PMID- 17041436
TI  - Transient renal dysfunction with Raynaud's phenomenon: is there a connection?
AB  - We describe a patient with an episode of severe Raynaud's phenomenon and early or
      mild scleroderma who presented with a transient elevation of her serum creatinine
      that resolved spontaneously after 2 days. Vascular response to cold temperatures
      has been described in vascular beds other than the extremities, and a similar
      phenomenon in the kidney might have been responsible for the transient renal
      dysfunction. Possible mechanisms to explain this phenomenon are discussed.
      Vasospasm merits consideration as an uncommon but largely reversible cause of
      elevated creatinine in patients with Raynaud's phenomenon.

PMID- 17041437
TI  - Relapsing polychondritis with involvement of posterior inferior cerebellar artery
      causing acute lateral medullary syndrome.
AB  - We present a patient with relapsing polychondritis who presented with findings of
      lateral medullary syndrome, known as the syndrome of Wallenberg, produced by
      infarction of a wedge of lateral medulla lying posterior to the inferior olivary
      nucleus. Angiographic examination showed complete occlusion of the right
      posterior inferior cerebellar artery and segmental narrowings in the basilar
      artery. We believe that the angiographic findings were based on an underlying
      vasculitis because of his relapsing polychondritis. This is the first case of
      relapsing polychondritis with angiographically demonstrated posterior inferior
      cerebellar artery involvement. Although this syndrome is usually a result of
      atherosclerosis, our case suggests that vasculitis must also be considered
      because it may respond to treatment with corticosteroids.

PMID- 17041438
TI  - Successful treatment with low-dose thalidomide in a patient with both Behcet's
      disease and complex regional pain syndrome type I: case report.
AB  - Thalidomide is a recognized treatment of Behcet's disease. Low-dose thalidomide
      seems to be effective in the treatment of orogenital ulcers and is potentially
      safer with a lower incidence of adverse effects than higher doses. We wish to
      report a case of Behcet's disease in a 33-year-old woman who responded well to
      thalidomide 50 mg 2 to 4 times per week. Her disease manifestations (severe
      orogenital ulceration, pseudofolliculitis, mild thrombophlebitis, positive
      pathergy response, and fatigue) were previously resistant to courses of
      prednisone, dapsone, colchicine, various types of mouthwash, and topical steroid
      preparations. She also gave a history of complex regional pain syndrome type I
      (CRPS 1) over her left patella (severe pain, intermittent edema, hyperalgesia,
      allodynia, cold skin, and loss of movement) after a fall onto her left knee 6
      years previously. This had only partially responded to a variety of treatment
      modalities. After starting thalidomide for her Behcet's disease, the pain in her
      left knee unexpectedly disappeared. There are rat experiments showing that
      thalidomide improves neuropathic pain, probably by selectively blocking tumor
      necrosis factor-alpha production in activated macrophages. We believe this is the
      first report of successful use of thalidomide in a human being with CRPS 1, and
      we therefore recommend that thalidomide should be considered in the treatment of
      CRPS 1.

PMID- 17041439
TI  - When thought leaders mislead: "discoid lupus is not related to SLE".

PMID- 17041440
TI  - Differentiating the new rheumatoid arthritis biologic therapies.
AB  - Current understanding of the mechanisms behind the pathogenesis of rheumatoid
      arthritis (RA) has led to the development of therapies involving biologic agents
      that target specific mediators of the disease process. Although the biologic
      agents used to treat RA share the ability to alter the cytokine cascade, they
      differ in ways that are clinically important. For example, they vary with regard
      to how they block cytokine activity (ie, as receptors, as receptor blockers, or
      as anticytokine antibodies) and the particular cytokine they target (eg, tumor
      necrosis factor [TNF] versus interleukin-1). Biologic therapies for RA also
      differ in mode of administration. Several are administered subcutaneously,
      whereas others are given intravenously. They also have molecular dissimilarities
      that result in differences in pharmacokinetics (ie, long versus medium half-life)
      and that may influence their safety profiles.Some biologic agents, such as the
      TNF inhibitors etanercept and infliximab, have been rigorously examined for long
      term safety and efficacy, whereas other agents, like the TNF inhibitor
      adalimumab, have not. Differences between the various biologic agents may relate
      to the usefulness of each individual drug as a long-term treatment in RA. For
      example, the need for physician visits may impact the practicality of drugs that
      are administered intravenously. Also, physicians should be aware that use of
      cytokine inhibitors increases the risk of infection. The prevalence of
      tuberculosis during therapy with infliximab exceeds the background rate in
      patients with RA. Accordingly, physicians should be familiar with the updated
      warnings in the package inserts that accompany these drugs.

PMID- 17041441
TI  - Examination of the risk of continuous leflunomide treatment on the incidence of
      infectious complications after joint arthroplasty in patients with rheumatoid
      arthritis.
AB  - SYNOPSIS: To determine whether the risk of infectious complications after total
      joint arthroplasty is increased in rheumatoid arthritis patients who are treated
      continuously with leflunomide, the incidences of infectious complications in 41
      rheumatoid arthritis patients who received continuous leflunomide treatment
      (leflunomide group) and in 41 patients who did not receive leflunomide within 4
      weeks of surgery (nonleflunomide group) were compared. The incidence (6.1%) of
      local infection after surgery in the leflunomide group (82 procedures) was
      slightly lower than that (6.3%) in the nonleflunomide group (79 procedures).
      There were no systemic or deep infections. None of the other variables analyzed
      were identified as risk factors for postoperative complications. The results
      indicate that there is no dramatically increased risk of postoperative infectious
      complications in rheumatoid arthritis patients who continue to be treated with
      low doses of leflunomide perioperatively.

PMID- 17041444
TI  - Acute inflammatory arthritis: an adverse effect of clopidogrel?

PMID- 17041442
TI  - Molecular biology and immunology for clinicians 23: autoimmunity and the
      superfamilies of tumor necrosis factor and tumor necrosis factor receptor.
AB  - The parsimony of nature can be stated as "if its not broke don't fix it, just
      tweak it and reuse it again and again." Nature recycles: once a motif is
      demonstrably useful it shows up again, often in unexpected places. Tumor necrosis
      factor and its receptor(s) are examples of this. At least 20 molecules have now
      been identified as being 25% homologous or more identical with tumor necrosis
      factor and being involved in a variety of immune and nonimmune functions. Members
      of the receptor superfamily have shared structural motifs and trigger shared
      intracellular signaling pathways. Rather than having been implicated in arcane
      and rare syndromes, some of these activities are pivotal in immune function and,
      when perturbed, some predispose to known immunodeficiency and autoimmune disease.
      Not surprisingly, some of these are becoming targets for immunomodulation. New
      members of these 2 superfamilies are currently being described and the newcomers
      and the "original stock" will show up in the clinic before you know it! Part of
      the confusion has always been that each laboratory describing a new biologic
      principle names the mediating compound. Thus, multiple labs, multiple names for
      the same protein (recall Ro/SS-A, La/SS-B). Thus, special attention is paid below
      to acronyms and their synonyms.

PMID- 17041445
TI  - Annular, semicircular lipoatrophy of the thighs associated with incomplete
      "CREST" syndrome: Raynaud's, telangiectasias, and esophageal dysmotility.

PMID- 17041447
TI  - Evaluating treatment efficacy: potential biases behind randomized controlled
      trials.

PMID- 17041448
TI  - Topical treatment of osteoarthritis of the knee with herbal products: promising
      results but still questions.

PMID- 17041449
TI  - The impact of disease activity on the quality of life, mental health status, and
      family dysfunction in colombian patients with rheumatoid arthritis.
AB  - This study investigated the relationship between activity of disease, mental
      health status, quality of life, and family dysfunction in northwestern Colombian
      patients with rheumatoid arthritis (RA). Seventy-nine patients completed a 2
      phase study that included physical examination (objective measurement of disease
      activity according to adapted American College of Rheumatology criteria) and a
      pretested questionnaire that sought information on helplessness, disability,
      depression, anxiety, quality of life, arthritis self-efficacy for pain, and other
      symptoms, as well as family dysfunction and socioeconomic status. Nineteen
      patients (24%) had active RA, 48 (61%) had moderately active RA, and 12 (15%)
      were in remission. Symptoms of depression, helplessness, disability, pain,
      anxiety, lower quality of life, and self-efficacy were associated with RA
      activity regardless of age, sex, and duration of the disease. Symptoms of
      depression were directly correlated with anxiety, helplessness, pain, and
      disability and inversely correlated with quality of life and self-efficacy.
      Although family dysfunction was present in 39% of patients, no associations
      between family dysfunction, activity of RA, mental health variables,
      socioeconomical status or quality of life were observed. These results indicate
      that RA activity significantly influences mental health status and quality of
      life in this population. Accordingly, a holistic conception of therapy should
      guide the treatment of patients with RA.

PMID- 17041450
TI  - The decreasing prevalence of uveitis associated with juvenile rheumatoid
      arthritis: do NSAIDs play a role?
AB  - We studied the prevalence and characteristics of chronic uveitis in a population
      of children diagnosed with juvenile rheumatoid arthritis (JRA). Uveitis is one of
      the most important, potentially debilitating extra-articular manifestations of
      JRA and has been observed in as many as 20% of cases. The medical records of 230
      patients diagnosed with JRA and treated at a tertiary care hospital ophthalmology
      clinic between 1992 and 2000 were retrospectively reviewed. Seventeen patients
      (7.4%) were found to have clinical features of uveitis. There was a preponderance
      of female patients (16/17) and pauciarticular disease (13/17). Only 12 of 17 were
      ANA positive. Six had uveitis at diagnosis. Patients who were receiving naproxen
      had less incidence of uveitis compared with those receiving other nonsteroidal
      antiinflammatory drugs. Despite a relatively low prevalence of uveitis,
      complications occurred in about 24% (4/17) of the patients, even with adequate
      treatment and close monitoring. The prevalence of uveitis in JRA seems to be
      decreasing and may be secondary to the increased use of naproxen. However,
      routine ophthalmologic screening should be continued in patients with JRA to
      avoid potential complications of chronic uveitis.

PMID- 17041451
TI  - Hypertension and elevated ESR as diagnostic features of Takayasu arteritis in
      children.
AB  - Takayasu arteritis (TA) is an inflammatory disease of the aorta and its branches.
      Delay in diagnosis is a common problem for adults and children. Although early
      manifestations are nonspecific (i.e., malaise, fever, anorexia, weight loss,
      myalgia, arthralgia/arthritis, elevated acute phase reactants), the clinical
      features that lead to diagnosis often appear suddenly and are related to vascular
      involvement. Hypertension, which is rare in children, and elevated ESR are found
      in most patients with TA. The authors hypothesized that these features, then,
      could be used as way to raise the clinical suspicion of TA. A total of 190 young
      patients with TA were retrospectively analyzed from local records and the
      literature to find the signs and symptoms associated with the disease that could
      be used to educate caregivers about when to suspect TA and to provide a screening
      tool for the disease. Hypertension and elevated ESR are found in most patients
      with TA. For this local study group, the sensitivity of this combination was 67%.
      Including the literature sources for which patient-specific information was
      available, the overall sensitivity was 65%. Thus, the combination of hypertension
      and elevated ESR in pediatric patients should merit further screening for TA,
      particularly in those with systemic complaints. Physical examination should focus
      on pulse abnormalities. Further evaluation should involve extensive imaging of
      the vascular system.

PMID- 17041452
TI  - Effect of a topical herbal cream on the pain and stiffness of osteoarthritis: a
      randomized double-blind, placebo-controlled clinical trial.
AB  - This study compared the efficacy of an herbal ointment to a placebo ointment in
      relieving the pain and stiffness of osteoarthritis. The herbal preparation
      contained substances believed by alternative practitioners to be helpful in
      treating osteoarthritis. This study was a double-blind randomized placebo
      controlled clinical trial. Subjects were solicited from patients attending an
      arthritis clinic in Dallas, Texas. Selection of subjects with osteoarthritis was
      based on the criteria developed by the American College of Rheumatology. Subjects
      were randomized to an active (n = 11) or a placebo (n = 8) group. Herbal ointment
      and control contained small amounts of capsaicin and menthol and were similar
      when applied. Subjects graded their levels of pain and stiffness for a 1-week no
      treatment baseline. Subjects then applied the herbal or sham ointment to the
      involved joint(s) for 28 consecutive days and recorded their levels of pain and
      stiffness daily on visual analog scales. Significant differences between the
      active and placebo groups for pain (P < 0.05) and stiffness (P < 0.05) were found
      when the baseline phase was compared with the fourth week. An herbal ointment was
      shown to be effective in relieving the pain and stiffness of osteoarthritis
      without adverse effects. If future studies confirm effectiveness of this
      treatment, it may have a role as an adjunct to standard drug therapy.

PMID- 17041453
TI  - Incidence of nonvertebral fractures in relation to time on treatment and bone
      density in glucocorticoid-treated patients: a retrospective approach.
AB  - The effects of duration of treatment and bone mineral density (BMD) on
      nonvertebral fracture in 560 glucocorticoid users were examined by using baseline
      and retrospective data from 2 parallel studies assessing the efficacy and safety
      of alendronate therapy. Baseline spine and hip BMD were significantly (P < 0.01)
      lower with increased time spent receiving glucocorticoids. Forty-three patients
      (7.7%) had experienced at least 1 nonvertebral fracture after starting
      glucocorticoid treatment. The hazard function for nonvertebral fracture
      occurrence increased significantly (P < 0.01) with time spent receiving
      glucocorticoids: fracture incidence per 1,000 person-years on glucocorticoids was
      18 (< 5 years), 31 (5-10 years), and 35 (> 10 years). Patients with a history of
      nonvertebral fractures after starting glucocorticoid treatment had significantly
      lower lumbar spine (P < 0.01) and hip (< 0.01) BMD value than those without
      fractures. This retrospective analysis suggests that a BMD measurement of spine
      and hip may identify risk for nonvertebral fractures in a heterogeneous
      population of glucocorticoid users.

PMID- 17041454
TI  - Reactivation of systemic lupus erythematosus after initiation of highly active
      antiretroviral therapy for acquired immunodeficiency syndrome.
AB  - As the demographics of human immunodeficiency virus (HIV) infection continue to
      include more African-American and Hispanic females, the prevalence of concomitant
      HIV infection and systemic lupus erythematosus (SLE) may increase. We describe a
      36-year-old woman with a 19-year history of active SLE who, after acquiring HIV
      infection, developed quiescent SLE with advanced immunosuppression (CD4 cell
      count 10/2%). After presenting with an opportunistic infection, she began
      receiving highly active antiretroviral therapy. Throughout a 6-month period,
      highly active antiretroviral therapy resulted in suppression of her viremia, as
      well as a concomitant rise in her CD4 cell count. With recovery of her immune
      status, she presented with transverse myelitis caused by her SLE, which responded
      well to intravenous steroids. There have been several observations of quiescence
      of lupus disease activity with advanced immunosuppression in HIV patients. This
      is a report of the recurrence of rheumatic disease in an acquired
      immunodeficiency syndrome patient after the initiation of highly active
      antiretroviral therapy. We recommend careful observation of HIV patients for
      reactivation of rheumatic disease while initiating highly active antiretroviral
      therapy.

PMID- 17041455
TI  - Subcutaneous nodules and joint deformity in leprosy: case report and review.
AB  - Leprosy (Hansen's disease), known to be caused by Mycobacterium leprae, is a well
      known illness with multiple rheumatologic manifestations. This chronic
      granulomatous infection has clinical features that are variable, depending on the
      immune response of the host. Manifestations consist mainly of involvement of the
      peripheral nerves, skin, upper respiratory system, eyes, and testes, as well as
      joints. Musculoskeletal manifestations include arthralgias, arthritis, Charcot
      arthropathy, and positive autoantibodies. We report a case of a Puerto Rican-born
      woman who was living within the northeastern United States and had subcutaneous
      nodules, saddle nose deformity, and painless contractures of her fingers and
      toes. This case illustrates some of the musculoskeletal manifestations of leprosy
      to raise awareness of this disease as part of the differential diagnosis of
      articular abnormalities with subcutaneous nodules in a nonendemic country.

PMID- 17041456
TI  - Underuse of intra-articular and periarticular corticosteroid injections by
      primary care physicians: discomfort with the technique.
AB  - Musculoskeletal disorders account for 11% to 13% of office visits in ambulatory
      care clinics and 9% of all physician visits in the United States. Intra-articular
      or periarticular aspiration or injections are an integral part of the management
      of arthritis or periarthritis. Our aim was to determine the use and level of
      comfort of administering intra-articular and periarticular injections by primary
      care physicians (PCPs) practicing in a university setting.A self-administered
      questionnaire with 20 questions querying experience and training in local
      injection therapy was mailed to 82 physicians (junior residents, senior
      residents, and faculty) offering primary care at the University of Chicago.
      Comfort scores were measured with a scale of 1 to 10 (1 = minimum and 10 =
      maximum). The response rate to the questionnaire was 67% (36 residents and 19
      faculty). Seventy-one percent of PCPs routinely suggested the procedure for
      severe arthritis and bursitis, but only 19% had (self-administered) performed it
      themselves. Eighty-nine percent of the PCPs referred their patients to specialty
      clinics. Forty-eight percent referred their patients to rheumatology, 11.5% to
      orthopedics, and 29% to both. Other PCPs were consulted for the procedure by
      9.6%. Discomfort with the performance of the technique was the predominant reason
      for 83% of the referrals. The mean comfort score for intra-articular or
      periarticular injections was 3.10 +/- 2.14 in general and 4.45 +/- 2.92 for knee
      joint. The mean comfort score for other joints and bursae ranged from 1.20 to
      2.15. Ninety-five percent of PCPs regarded themselves to be inadequately trained.
      Regarding the training, 41% had received a lecture during medical school and
      residency, while 40% had received demonstration of the techniques during
      residency. Of the faculty, 26% had never received any formal lecture, and 5.2%
      had never received formal demonstration of the techniques during their training.
      Joint injections observed ranged from 89% for knee to 59% for shoulder and 22%
      for wrist joints. Only 11% of faculty had performed more than 5 intra-articular
      injections during their training. A need for formal training in these techniques
      was identified by 95% of the subjects, of whom 65% thought the residency period
      was the best time to do so. Performing 5 to 10 intra-articular injections during
      residency was considered optimal training by 60%. On subanalysis, the mean
      comfort scores were higher in the residents in general (3.60 +/- 2.29 versus 2.18
      +/- 1.47;P = 0.01) as compared with faculty. The residents' scores were also
      higher across different joints as compared with those of faculty but assumed
      statistical significance only for olecranon bursa injection (2.32 +/- 2.76 versus
      1.27 +/- 0.67;P = 0.04) and subacromial bursa injection (2.08 +/- 2.27 versus
      1.27+/- 0.75;P = 0.06). The mean comfort scores were lower by 1.74 (P = 0.007)
      for women physicians. There is underuse of self-administered intra-articular and
      periarticular injection techniques by PCPs in the management of arthritis or
      periarthritis. The reasons include inadequate training and low comfort in
      performing these procedures. Eighty-nine percent of PCPs would refer their
      patients to subspecialty clinics for these "routine" injections. There is a clear
      need for a training in these procedures during residency.

PMID- 17041457
TI  - Evidence-based soft tissue rheumatology. Part I: subacromial impingement
      syndrome.
AB  - Impingement into the coracoacromiohumeral space, a common cause of rotator cuff
      tendinopathy, may result from an impinging osteoligamentous upper boundary,
      abnormalities in the tendon itself, or failure of muscles that retain the humeral
      head on the glenoid. An overuse mechanism is clearly a risk factor in throwing
      athletes, whereas occupational overuse may contribute to its development in
      nonathletes. The subacromial anesthetic injection test remains as the
      acknowledged gold standard for diagnosis. There is evidence on the therapeutic
      efficacy of nonsteroidal antiinflammatory drugs, glucocorticoid subacromial
      injection, and acupuncture as compared with placebo. Also, acromioplasty appears
      to be better than physiotherapy. Patients with rotator cuff tendinopathy may be
      successfully treated with nonsteroidal antiinflammatory drugs, a glucocorticoid
      subacromial injection, or acupuncture. In failures of conservative therapy,
      surgery should be considered. Further research is required on etiology,
      diagnosis, natural course, and validity of many treatments currently used in this
      common condition.

PMID- 17041458
TI  - Molecular biology and immunology for clinicians 24: phylogeny of the immune
      system.
AB  - The human immune system consists of layer upon layer of response, communication,
      and coordination mechanisms added during its evolution throughout the last half
      billion years. Given the parsimony of nature, it is not surprising that many of
      the systems prominent within the human immune response are recognizable within
      the immune systems of less advanced species. Insights drawn from these species
      and common sense suggest that "autoimmune" reactivity was not the original or
      primary reason for the evolution of these mechanisms. Also, it becomes clear that
      certain functions thought to be "immune" may actually be nonspecific, really
      innate functions served by these ancient mechanisms. There is good evidence of
      communication between levels of the immune system, the innate and adaptive
      systems working with each other, often the former (not antigen-specific)
      preceding and serving to trigger or magnify the latter (antigen-specific). A
      future article in this series will focus more on the innate system and how it
      interdigitates with the adaptive system.

PMID- 17041459
TI  - Pseudogout and gout in a patient after liver transplantation for primary biliary
      cirrhosis: what might be the association?

PMID- 17041460
TI  - Use of a dopamine against in fibromyalgia: where is the evidence?

PMID- 17041461
TI  - Influence of leflunomide on renal handling of urate and phosphate in patients
      with rheumatoid arthritis.
AB  - Reduction of serum urate and phosphate levels has been observed in patients
      receiving leflunomide therapy, but the mechanism for such changes has not been
      evaluated. Thirty-eight patients with rheumatoid arthritis who began leflunomide
      were studied. Serum urate, creatinine, and phosphate, and 24-hour uric acid,
      creatinine, and phosphate were measured before, during, and in some instances
      after leflunomide treatment. Clearances of urate and creatinine, fractional
      excretion of urate, and tubular reabsorption of phosphate were calculated.
      Undissociated urinary uric acid was estimated with a nomogram. Twelve patients
      gave consent to withdraw leflunomide treatment of a 2-week period and underwent a
      third study. Decreases in serum urate and phosphate levels were observed, with
      parallel increases in clearances of urate and in fractional excretion of urate,
      and a reduction in tubular reabsorption of phosphate. Clearances of creatinine
      and undissociated urinary uric acid remained unchanged. Two weeks after
      withdrawing the drug, a partial return toward baseline values was observed, but
      residual changes were apparent. No case of clinical gout was observed.
      Leflunomide enhances urate and phosphate loss, an effect that partially persisted
      after 2-week withdrawal. The long-term effect of mild phosphate wasting warrants
      further investigation. The urate-lowering effect of leflunomide may be useful in
      monitoring compliance in leflunomide therapy.

PMID- 17041462
TI  - Abnormalities of bone mineral density and bone metabolism in Venezuelan patients
      with rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at increased risk for osteoporosis
      and bone fractures. To our knowledge, the frequency of osteopenia and
      osteoporosis in patients with RA from Latin America has not been established. In
      this study, we have examined the bone mineral density (BMD) by dual-energy x-ray
      absorptiometry, as well as biochemical markers of bone metabolism, in a
      population of 85 Venezuelan RA patients. Twenty-seven patients (29.4%) fulfilled
      the World Health Organization's (WHO) criteria for either trabecular osteopenia
      or osteoporosis compared with 10 healthy controls (8.1%; odds ratio [OR] = 3.25;
      P = 0.004). In addition, 30 patients (26.4%) showed cortical osteopenia or
      osteoporosis compared with 5 healthy controls (4.0%; OR = 8.18; P < 0.00001).
      Past or concurrent use of prednisone or methotrexate was not related to decreased
      BMD. Rheumatoid patients showed increased serum levels of osteocalcin (P = 0.002)
      and 24-hour urine excretion of N-telopeptide cross-links (P = 0.03). The bone
      marker profiles suggest an increased bone turnover during the premenopausal stage
      in these patients. After menopause, a resorptive pattern seems to predominate,
      leading to accelerated bone mass loss in RA patients. In conclusion, Venezuelan
      female patients with RA may be at increased risk for osteopenia or osteoporosis,
      particularly after menopause. Our study supports the initiation of antiresorptive
      medication in Latin American premenopausal patients with RA, as in other ethnic
      groups, to diminish the risk of osteoporosis in the postmenopausal stage.

PMID- 17041463
TI  - A look at rheumatology in China (2002).
AB  - This report describes a visit by an international group interested in
      Rheumatology to the Rheumatology centers and traditional Chinese medicine units
      in the People's Republic of China. Differing disease patterns and treatment
      approaches offer opportunities for studies and collaborations. We can also learn
      from the traditional Chinese approach with individualization of therapy and
      attention to health maintenance.

PMID- 17041464
TI  - Bronchiolitis obliterans with organizing pneumonia associated with scleroderma
      and scleroderma spectrum diseases.
AB  - Systemic sclerosis (SSc) is an autoimmune disorder with a high mortality rate
      from pulmonary manifestations, such as interstitial lung disease and pulmonary
      hypertension, seen at autopsy in 90% and 75% of patients, respectively.
      Bronchiolitis obliterans with organizing pneumonia (BOOP) has numerous causes,
      but it has only been reported in three patients with SSc. We present three cases
      of biopsy-proven BOOP in patients with scleroderma spectrum disease, including
      diffuse cutaneous SSc, mixed connective tissue disease with SSc features, and
      limited cutaneous SSc that later evolved to dermatomyositis/SSc overlap. BOOP and
      SSc alveolitis have similar findings on spirometry, radiographs, and BAL; the
      definitive diagnosis of BOOP was therefore made by open lung biopsy.
      Cyclophosphamide is the current treatment of alveolitis associated with SSc,
      whereas high-dose prednisone is used to treat BOOP. As a result of this
      difference, we emphasize the importance of a thorough investigation of pulmonary
      disease in SSc patients to exclude BOOP and treat appropriately.

PMID- 17041465
TI  - Cavitary necrobiotic nodule imitating malignant lung disease in a patient without
      articular manifestations of rheumatoid arthritis.
AB  - Pulmonary involvement is a serious complication of rheumatoid arthritis (RA) and
      may be seen as airway disease, rheumatoid nodules, interstitial lung disease, and
      pleurisy. However, cavitary rheumatoid nodules without articular manifestations
      are rare. We describe a male patient presenting with pleurisy and multiple
      rheumatoid necrobiotic nodules in the absence of arthritis or subcutaneous
      nodules. One of the nodules was quite large (5 x 8 cm in diameter) and cavitary,
      imitating bronchial carcinoma radiologically and bronchoscopically. Definite
      histopathologic diagnosis was obtained by open lung biopsy. The patient was given
      methylprednisolone and methotrexate, and significant regression was observed in
      clinical and radiologic findings. He has been followed for 14 months with no
      articular manifestations yet, receiving 4 mg/d methylprednisolone and 20 mg/wk
      methotrexate. The diagnosis of rheumatoid pulmonary involvement without articular
      manifestations can be difficult. Rheumatoid nodules may imitate bronchial
      carcinoma, or bronchial carcinoma may coexist in RA patients. Open lung biopsy
      may be necessary for differential diagnosis of pulmonary lesions in RA.

PMID- 17041466
TI  - Macrophage activation syndrome in a patient with systemic onset rheumatoid
      arthritis: rescue with intravenous immunoglobulin therapy.
AB  - We report the case of a 7-year-old boy with systemic onset juvenile rheumatoid
      arthritis (JRA) who developed macrophage activation syndrome during a period of
      relative remission. He presented with high-grade fever, enlarged lymph nodes,
      acute hepatitis, severe pancytopenia, and evidence of disseminated intravascular
      coagulopathy. He became severely ill, with persistent mucosal bleeding,
      hypovolemia, and vascular instability, and he was admitted to the intensive care
      unit. No response was observed to treatment with high-dose intravenous
      corticosteroids and blood product replacements, but the patient fully recovered
      after the completion of two pulses of intravenous immunoglobulin. This treatment
      modality may be an alternative to anti-TNF-alpha and cyclosporine A for a prompt
      response in JRA patients with this potentially fatal condition.

PMID- 17041467
TI  - Panniculitis: a presenting manifestation of disseminated histoplasmosis in a
      patient with rheumatoid arthritis.
AB  - We report a case of histoplasma panniculitis in a patient with rheumatoid
      arthritis treated with multiple immunosuppressive agents including infliximab.
      The patient presented with erythematous plaques involving the right upper
      anterior abdominal wall, the right flank and later extension to involve the left
      flank and the left axilla. The histopathologic examination of these lesions was
      consistent with lobular panniculitis and the cultures of these lesions and blood
      grew Histoplasma capsulatum. The clinical and histopathologic picture of
      histoplasma panniculitis and rheumatoid arthritis-associated panniculitis can be
      very similar, but the treatment is clearly different. Our case emphasizes the
      importance of considering rare manifestations of opportunistic infections in an
      era of widespread use of immunosuppressive medications in the field of
      rheumatology.

PMID- 17041468
TI  - Refractory pulmonary hypertension in a lupus patient with occult pulmonary
      vasculitis.
AB  - Primary pulmonary hypertension is a disease that has become increasingly
      recognized in lupus patients. Pathologic findings from lupus patients usually do
      not differ from those who have idiopathic pulmonary hypertension. In recent
      years, intravenous vasodilator therapy has improved morbidity and mortality in
      patients with primary pulmonary hypertension. In this case report, we describe a
      young woman with severe pulmonary hypertension refractory to aggressive
      parenteral vasodilator treatment. Steroid treatment was initiated after a
      tentative diagnosis of lupus was made on the basis of the presence of Raynaud's
      phenomenon, proteinuria, pericarditis with tamponade, and a positive anti-Ro
      antibody. Despite treatment with vasodilators and steroids, the patient's
      condition rapidly deteriorated and she died. Unexpectedly, active pulmonary
      arteritis was demonstrated at autopsy. This case suggests that immunosuppressive
      therapy should be considered in lupus patients with severe pulmonary hypertension
      who are refractory to aggressive vasodilator therapy and high-dose parenteral
      steroids.

PMID- 17041471
TI  - Crohn disease worsened by anakinra administration.

PMID- 17041469
TI  - Molecular biology and immunology for clinicians 25: defense collagens.
AB  - The adaptive immune response specializes in reacting efficiently and rapidly with
      protein antigens. Many pathogens and host cells are coated with carbohydrates
      (more about lipid antigens and the response thereto in a future installment of
      this series). The carbohydrate arrays on pathogens are remarkable for their
      relative lack of diversity, remarkable conservation, and how different they are
      from the carbohydrates found on mammalian cells. Thus, they represent excellent
      targets for the innate immune response, which is characterized by limited
      effector molecule heterogeneity. Defense collagens are a class of innate immune
      response recognition proteins targeting these common carbohydrate motifs, a class
      you may not have encountered previously. These invariant germ-line encoded
      proteins are not produced as a specific response to a particular antigen.
      Nonetheless, they too have an antigen-binding site, called the carbohydrate
      recognition domain with the other end of the molecule (made up of collagen-like
      domains) devoted to the transmission of biologically relevant information,
      analogous with the antibody molecule's Fc component, but this is where the
      similarities end. Defense collagens have been broadly viewed as an "anti
      antibody," broadly similar in structure and function. Despite the fact that they
      are germline-encoded and do not have individual antigen specificity, their
      phylogenetic longevity and durability prove the value of defense collagens in
      maintaining the host. On the basis of emerging studies, they may play important
      roles in the defense against many pathogens and in the pathogenesis of
      rheumatologic and other diseases. Thus, they are good targets for studies to
      better understand our diseases and to craft therapeutic manipulations in the
      future.

PMID- 17041472
TI  - Ropinirole, open preliminary observations of a dopamine agonist for refractory
      fibromyalgia.

PMID- 17041473
TI  - Comment on Furst's editorial: postmarketing surveys: up sides and down sides.

PMID- 17041475
TI  - Possible relationship between AA amyloidosis and decreased complements in
      patients with rheumatoid arthritis.

PMID- 17041476
TI  - Modafinil for the treatment of fatigue of fibromyalgia.

PMID- 17041477
TI  - Rheumatoid nodulosis: a diagnostic dilemma.

PMID- 17041478
TI  - Are isolated antinucleolar antibodies a marker of scleroderma?
AB  - This study was designed to determine the prevalence and positive predictive value
      of isolated antinucleolar antibody (ANA) in scleroderma patients. We identified
      73 rheumatology clinic patients with isolated ANAs. ANA titers greater than 1:160
      were considered positive. The overall prevalence of isolated ANAs was 2.9%. The
      prevalence of isolated ANAs in scleroderma, systemic lupus erythematosus (SLE),
      and rheumatoid arthritis were 20.3%, 2.68%, and 3.3%, respectively. Scleroderma
      and SLE were present in 12 patients (16.4%) each. Other rheumatologic disorders
      identified in these patients were RA (12.3%), undifferentiated connective tissue
      disease (8.2%), mixed connective tissue disease (4.1%), vasculitis (6.8%),
      fibromyalgia (8.2%), osteoarthritis (5.4%), crystal-related arthropathy (6.8%),
      seronegative arthritis (2.7%), sarcoidosis (4.1%), and others (8.2%). There were
      no statistically significant differences in the median ANA titers in scleroderma
      versus systemic lupus (P = 0.16) or undifferentiated connective tissue disease (P
      = 0.18). The median titers were higher in scleroderma in comparison with
      rheumatoid arthritis (P = 0.01), osteoarthritis (P = 0.007), fibromyalgia (P =
      0.001), and crystal-related arthropathy (P = 0.009). Isolated ANAs have poor
      sensitivity (20.3%) and the positive predictive value for this test is only 16.4%
      for scleroderma.

PMID- 17041479
TI  - Rheumatoid nodulosis: is it a different subset of rheumatoid arthritis?
AB  - Rheumatoid nodulosis is an entity that describes a particular variant of
      polyarthritis associated with early manifestations of palindromic rheumatism,
      radiologic subchondral bone cysts, and subcutaneous rheumatoid nodules. This
      study describes the clinical, radiologic, histologic, crystallographic, and
      laboratory findings, as well as the outcome in a group of 16 patients with
      rheumatoid nodulosis that were followed for a period of 1-12 years. Six of these
      patients had an aggressive course and developed classic erosive polyarticular
      rheumatoid arthritis, while the others continued having episodic arthritis
      without erosive disease. Seven patients had cholesterol crystals in olecranon
      bursae containing nodules. Second-line drugs used to control the articular
      manifestations did not improve the nodulosis, erosive, or cystic subchondral bone
      changes. Rheumatoid nodulosis mimics several other rheumatic diseases, and in
      about 40%, classic erosive rheumatoid arthritis develops. The presence of
      cholesterol crystals in rheumatoid nodules or affected bursae can increase the
      confusion with other crystal-induced arthritis, in particular, tophaceous
      monosodium urate gout or xanthomatosis.

PMID- 17041480
TI  - Persistent hiccups associated with intravenous corticosteroid therapy.
AB  - Singulata, commonly known as hiccups, have many causes and are most often
      idiopathic and short-lived. Occasionally, hiccups can be persistent and becoming
      quite bothersome, distracting, and even disabling. Many medications have been
      implicated as a cause of hiccups. Although uncommon, corticosteroids and
      benzodiazepines are 2 classes of drugs most frequently associated with the
      development of hiccups. The following case series describes 5 patients with
      intravenous corticosteroid-associated hiccups reported to our adverse drug
      reaction reporting system between January 1998 and December 2000. Physicians
      using intravenous corticosteroids should be aware of this potential complication.

PMID- 17041481
TI  - The use of topical tacrolimus (FK506/Protopic) in cutaneous manifestations of
      autoimmune diseases.
AB  - The cutaneous manifestations of autoimmune diseases, including systemic lupus
      erythematosus, are common and often recalcitrant to treatment. Unfortunately,
      therapy for lupus and other autoimmune skin diseases has not advanced and relies
      heavily on the use of oral and topical corticosteroids. Frequently, treatments
      prove less than ideal, either from toxicity or lack of efficacy. A topical form
      of the immunomodulating transplant medication, tacrolimus (FK-506, Protopic), has
      recently been developed and approved for use in treating atopic dermatitis. Its
      mechanism of action and local route of administration render tacrolimus a
      potentially attractive novel therapeutic alternative for the treatment of various
      autoimmune dermatologic conditions. We report our successful experience using
      this drug in 3 patients with autoimmune dermatologic disease who were referred to
      a tertiary care subspecialty clinic.

PMID- 17041482
TI  - Valvular disease and myocardial infarctions in a patient with Behcet disease.
AB  - Cardiac involvement occurs in less than 5% of Behcet patients, and coincidence of
      regurgitation of the aortic and mitral valves and myocardial infarctions is rare.
      This report describes a 49-year-old Turkish man with Behcet disease (BD) of 6
      years' duration who presented with reduced left ventricular function. Both aortic
      and mitral valves had to be replaced. Five months later, the patient presented
      with non-ST segment elevation myocardial infarction. Only 1 month later, the
      patient was successfully resuscitated after an acute ST segment elevation
      inferior myocardial infarction. Coronary arteries were normal in appearance at
      angiography before valvular replacement and at autopsy 2 years later. This report
      should increase awareness of cardiac involvement in BD and its potential danger.
      Even in BD patients without atherothrombotic plaques, myocardial infarctions can
      happen. Early and adequate immunosuppressive treatment might have reduced cardiac
      morbidity in this patient.

PMID- 17041483
TI  - The management of chronic noninfectious synovitis ca. 1818.

PMID- 17041484
TI  - A case of isolated sacral and pelvic sarcoidosis diagnosed by bone marrow biopsy.
AB  - Although sarcoidosis frequently involves bone, it rarely presents as isolated
      osseous disease. We present a case in which sarcoidosis is limited to the sacrum
      and pelvis, a case that underscores the potential importance of both magnetic
      resonance imaging (MRI) and bone marrow biopsy in establishing the diagnosis.
      Additionally, we report the interval resolution of bony disease by MRI following
      glucocorticoid treatment.

PMID- 17041485
TI  - Resource-Based Relative Value Scale (RBRVS): a useful tool for practice analysis.
AB  - This system determines Medicare reimbursement in the USA but also may provide
      information to help analyze your practice. Since being implemented in 1992, the
      Resource- Based Relative Value Scale (RBRVS) has been the basis of all physician
      reimbursement from Medicare and increasingly is being used by other third-party
      payers to determine physician payments. The development of the RBRVS dates back
      to the 1980s and has evolved to the current system. Besides its use in physician
      reimbursement, by virtue of its nationwide usage, RBRVS has become a tool by
      which physicians can compare practice volume and efficiency, both with respect to
      other practices and within a single practice, to compare individual physicians.
      Although seemingly complex, the RBRVS provides a useful tool for physicians to
      understand their productivity, contracting, and reimbursement.

PMID- 17041486
TI  - 85-year-old retired welder.

PMID- 17041487
TI  - Successful treatment of a patient with refractory adult-onset still disease with
      anakinra.

PMID- 17041488
TI  - A pilot trial of external Qigong therapy for arthritis.

PMID- 17041489
TI  - Surgical anatomy of microneurosurgical sulcal key points.
AB  - OBJECTIVE: The brain sulci constitute the main microanatomic delimiting landmarks
      and surgical corridors of modern microneurosurgery. Because of the frequent
      difficulty in intraoperatively localizing and visually identifying the brain
      sulci with assurance, the main purpose of this study was to establish
      cortical/sulcal key points of primary microneurosurgical importance to provide a
      sulcal anatomic framework for the placement of craniotomies and to facilitate the
      main sulci intraoperative identification. METHODS: The study was performed
      through the evaluation of 32 formalin-fixed cerebral hemispheres of 16 adult
      cadavers, which had been removed from the skulls after the introduction of
      plastic catheters through properly positioned burr holes necessary for the
      evaluation of cranial-cerebral relationships. Three-dimensional anatomic and
      surgical images are displayed to illustrate the use of sulcal key points.
      RESULTS: The points studied were the anterior sylvian point, the inferior
      rolandic point, the intersection of the inferior frontal sulcus with the
      precentral sulcus, the intersection of the superior frontal sulcus with the
      precentral sulcus, the superior rolandic point, the intersection of the
      intraparietal sulcus with the postcentral sulcus, the superior point of the
      parieto-occipital sulcus, the euryon (the craniometric point that corresponds to
      the center of the parietal tuberosity), the posterior point of the superior
      temporal sulcus, and the opisthocranion, which corresponds to the most prominent
      point of the occipital bossa. These points presented regular neural and cranial
      cerebral relationships and can be considered consistent microsurgical cortical
      key points. CONCLUSION: These sulcal and gyral key points can be particularly
      useful for initial intraoperative sulci identification and dissection. Together,
      they compose a framework that can help in the understanding of hemispheric lesion
      localization, in the placement of supratentorial craniotomies, as landmarks for
      the transsulcal approaches to periventricular and intraventricular lesions, and
      in orienting the anatomic removal of gyral sectors that contain infiltrative
      tumors.

PMID- 17041490
TI  - An anatomical evaluation of the mini-supraorbital approach and comparison with
      standard craniotomies.
AB  - OBJECTIVE: To compare anatomically the surgical exposure provided by pterional
      (PT), orbitozygomatic (OZ), and minisupraorbital (SO) craniotomies. METHODS:
      Seven sides of six fixed cadaver heads injected with silicone were used. The mini
      SO craniotomy followed by the PT and OZ approaches were performed sequentially.
      The bony flaps were attached with miniplates and screws, allowing easy conversion
      between the approaches. A frameless stereotactic device was used to calculate an
      area of surgical exposure and the angles of approach for six different anatomic
      targets. An image guidance system was used to demonstrate the limits of the
      surgical exposure for each technique. RESULTS: No significant differences were
      observed in the total area of surgical exposure when comparing the mini-SO (A =
      1831.2 +/- 415.3 mm), PT (A = 1860.0 +/- 617.2 mm), and OZ approaches (A = 1843.3
      +/- 358.1 mm; P > 0.05). Angular exposure was greater for the OZ and PT
      approaches than for the mini-SO approach, either in the vertical and horizontal
      axes, considering all of the six targets studied (P < 0.05). Except for the
      distal segment of the ipsilateral sylvian fissure, no practical differences in
      the limits of the exposure were detected. CONCLUSION: The mini-SO approach may
      offer a similar surgical working area compared with that provided by standard
      craniotomies and constitutes an excellent alternative to the OZ and PT
      craniotomies in selected patients. Selection should not be based primarily on the
      area to be exposed, but rather on the working angles that are anticipated to be
      required. The key point is to use the most adequate technique for a particular
      patient, rather than using a one-size-fits-all approach for all patients.

PMID- 17041491
TI  - Gray matter overlying anterior basal temporal sulci as an intraoperative landmark
      for locating the temporal horn in amygdalohippocampectomies.
AB  - OBJECTIVE: Use of the gray matter overlying the anterior portions of the
      occipitotemporal and rhinal sulci as an intraoperative landmark for locating the
      temporal horn during amygdalohippocampectomies approached by the superior or
      lateral surface of the temporal lobe. METHODS: The presence of occipitotemporal
      and rhinal sulci was analyzed in the magnetic resonance imaging scans of 165
      patients who subsequently underwent mesial temporal resections, focusing on
      coronal slices up to 4 cm from the temporal pole. These sulci were used during
      surgery to locate the temporal horn in 150 surgeries. Five adult cadaveric heads
      whose vessels were perfused with colored silicone were used for photography.
      RESULTS: These sulci are the principal sulci of the anterior basal temporal lobe.
      They were present in 154 out of 165 and 165 out of 165 patients, respectively.
      When approaching mesial temporal structures from the superior or lateral surface
      of the temporal lobe, dissection is initially performed through the white matter
      toward the floor of the middle fossa until the gray matter overlying an anterior
      basal sulcus is encountered. Dissection continues medially and superiorly from
      the top of the gray matter until the temporal horn is entered. CONCLUSION: Gray
      matter overlying these sulci leads toward the anterior portion of the floor of
      the temporal horn and constitutes a landmark for locating the temporal horn.
      However, only the rhinal sulcus was always present. When both are present, the
      gray matter overlying the occipitotemporal sulcus is a reliable landmark. These
      landmarks are most suitable for mesial temporal resections without significant
      displacement of the temporal horn.

PMID- 17041492
TI  - Meyer's loop and the optic radiations in the transsylvian approach to the
      mediobasal temporal lobe.
AB  - OBJECTIVE: In the transsylvian approach to the mediobasal temporal structures,
      the temporal horn is approached through the floor of the sylvian fissure. The
      anterior bundle of the optic radiations (Meyer's loop) courses between the floor
      of the sylvian fissure and roof of the temporal horn and could be damaged in this
      approach. This study was designed to define the route through the floor of the
      sylvian fissure least likely to damage the optic pathways. METHODS: Meyer's loop
      was dissected by applying Klingler's fiber dissection technique in 10 formalin
      fixed human hemispheres. Several measurements quantified the relationship of the
      Meyer's loop to surgically important structures. RESULTS: This study identified a
      triangular safe area below the floor of the sylvian fissure through which the
      temporal horn could be accessed in the transsylvian approach with a low risk of
      damaging the optic radiations. An incision in the floor of the sylvian fissure
      directed downward at the level of limen insula and the adjacent 5 mm of the
      inferior insular sulcus would avoid the optic radiations. An incision directed
      straight downward 10, 15, and 20 mm behind the limen in the inferior insular
      sulcus would cross Meyer's loop and would need to be directed downward and
      medially as much as 80 degrees from the sagittal plane to avoid Meyer's loop.
      CONCLUSION: In the transsylvian approach to the temporal horn, incisions at the
      level of the limen, or adjacent 5 mm of the inferior insular sulcus, are less
      likely to damage Meyer's loop and the optic radiations than more posterior
      incisions along the inferior insular sulcus. Incision at this safe level commonly
      opens into the amygdala, a portion of which is removed to provide entry into the
      temporal horn for removal of the mediobasal structures.

PMID- 17041493
TI  - The endoscopic endonasal approach to the lateral recess of the sphenoid sinus via
      the pterygopalatine fossa: comparison of endoscopic and radiological landmarks.
AB  - OBJECTIVE: The endoscopic endonasal approach offers the opportunity to reach the
      pterygopalatine fossa, the lateral recess of the sphenoid sinus, and other areas
      of the cranial base through a minimally invasive approach. This study compares
      the anatomy of these areas when observed through an endoscopic endonasal view
      with the anatomy of the same regions as they appear in computed tomographic
      scans. The aim was to identify and correlate the corresponding anatomic
      structures, providing the surgeons with anatomic landmarks to guide them when
      operating in these areas through an endoscopic endonasal approach. METHODS: An
      anatomic dissection of six fixed cadaver heads was performed by an endoscopic
      endonasal approach. A step-by-step comparison of endoscopic and radiological
      images was made to identify the landmarks of the surgical field. RESULTS: The
      step-by-step comparison of endoscopic and radiological images acquired during the
      endoscopic endonasal approach to the lateral recess of the sphenoid sinus via the
      pterygopalatine fossa allowed the identification of all the relevant anatomic
      landmarks of the procedure. CONCLUSION: The endoscopic endonasal approach via the
      pterygopalatine fossa offers direct, minimally invasive access to the lateral
      recess of the sphenoid sinus, which can be monitored in each phase through
      consistent radiological imagery.

PMID- 17041494
TI  - The supratonsillar approach to the inferior cerebellar peduncle: anatomy,
      surgical technique, and clinical application to cavernous malformations.
AB  - OBJECTIVE: To introduce the supratonsillar approach, an approach that traverses
      the tonsillobiventral fissure in a trajectory over the cerebellar tonsil to the
      inferior cerebellar peduncle, and to demonstrate the utility of this approach for
      resecting peduncular cavernous malformations. METHODS: Anatomy of the cerebellar
      tonsil and surrounding fissures, arteries, and veins are reviewed using cadaveric
      brain specimens. The surgical approach uses the three-quarter prone position, a
      suboccipital craniotomy, and wide splitting of the tonsillobiventral fissure.
      RESULTS: Of our experience with 171 patients with cavernous malformations, six
      patients had lesions in the inferior cerebellar peduncle that were resected using
      the supratonsillar approach. All cavernous malformations were removed completely
      and no patients experienced surgical complications or new deficits. CONCLUSION:
      The supratonsillar approach differs from the transvermian and telovelar
      approaches to the fourth ventricle, with a more superolateral trajectory that
      leads instead to the inferior cerebellar peduncle. By splitting the
      tonsillobiventral fissure and mobilizing the tonsil inferomedially, the point of
      access to the lesion is deepened and transgression of normal cerebellar tissue is
      minimized. This elegant approach is ideally suited to the removal of cavernous
      malformations.

PMID- 17041495
TI  - Extradural anterior clinoidectomy as an alternative approach for optic nerve
      decompression: anatomic study and clinical experience.
AB  - OBJECTIVE: We introduce pterional craniotomy extradural anterior clinoidectomy as
      a new alternative approach for optic nerve decompression in patients with
      traumatic optic neuropathy. METHODS: Intracranial structures pertinent to
      pterional craniotomy extradural anterior clinoidectomy were carefully studied in
      10 dry craniums and 10 cranial bases with dura mater. Important parameters of
      these structures were measured. Stepwise dissections simulating pterional
      craniotomy extradural anterior clinoidectomy were performed in 20 cadaver heads
      bilaterally. Pterional craniotomy extradural anterior clinoidectomy was then
      applied to 12 patients (13 eyes) with traumatic optic neuropathy and severe
      visual dysfunction. RESULTS: The anatomic features and their variations of optic
      canal, ophthalmic artery, falciform ligament, and Zinn's ring (annular tendon)
      were studied and measured in detail. Extensive opening of the optic canal and
      optic nerve sheath was successfully achieved in all 12 patients without major
      surgical complications. Significant visual acuity improvement occurred in eight
      (nine eyes) out of our 12 patients after surgery. The surgical techniques and
      advantages of pterional craniotomy extradural anterior clinoidectomy for optic
      nerve decompression are presented and discussed in detail. CONCLUSION: Pterional
      craniotomy extradural anterior clinoidectomy is a promising new alternative
      approach for optic nerve decompression in patients with traumatic optic
      neuropathy.

PMID- 17041496
TI  - The pterional-transsylvian approach: an analytical study.
AB  - OBJECTIVE: Splitting of the sylvian fissure (SF) improves exposure with the
      pterional (PT) approach. Traditionally, the choice of whether or not to split the
      SF and how far to open it has depended on the neurosurgeon's experience and
      preference rather than on quantifiable data. We undertook this study to evaluate
      the effects of progressive splitting of the SF on surgical exposure with the PT
      approach. METHODS: A PT craniotomy was performed on nine sides of cadaver heads.
      Splitting the SF was divided into four steps: 1) dissection of the basal
      cisterns, 2) dissection of the sphenoidal compartment, 3) dissection of the
      operculoinsular compartment to the anterior ascendant ramus, and 4) dissection
      progressing 2.0 cm distal to the anterior ascendant ramus. The degree of the
      retraction and the relative position of the brain retractors were kept constant.
      After each step, we used a computerized tracking system to measure the area of
      surgical exposure of the circle of Willis, the angles of approach to the carotid
      bifurcation, and the distance between the frontal lobe and skull base. RESULTS:
      Exposure of the circle of Willis, angles of approach to the carotid bifurcation,
      and linear distance between the frontal lobe and skull base all increased
      significantly as splitting of the SF progressed from Steps 1 to 2 and from Steps
      2 to 3. There was no significant difference between Steps 3 and 4. CONCLUSION:
      Exposure of the basal cisterns and circle of Willis by the PT approach is
      optimized when dissection of the SF reaches the anterior ascendant ramus. Further
      splitting of the SF provides no additional gain.

PMID- 17041497
TI  - The subtemporal interdural approach to dumbbell-shaped trigeminal schwannomas:
      cadaveric prosection.
AB  - OBJECTIVE: Successful resection of dumbbell-shaped trigeminal schwannomas via a
      subtemporal interdural approach requires an understanding of both the anatomy
      related to the bone dissection of the petrous apex (Kawase's triangle or
      quadrilateral) and meningeal anatomy. We studied the meningeal anatomy related to
      this approach and describe the dural incisions and stepwise mobilization.
      METHODS: Meningeal anatomy around Meckel's cave and porus trigeminus was examined
      during the subtemporal interdural anterior transpetrosal approach in both sides
      of 15 cadaveric heads. Histological study of the Meckel's cave region was
      performed in two cadaveric heads. RESULTS: The Gasserian ganglion and trigeminal
      roots have two layers of dura propria on their dorsolateral surface: an inner
      layer from the posterior fossa dura propria that constitutes the dorsolateral
      wall of Meckel's cave and an outer layer from the dura propria of the middle
      fossa. The cleavage plane between these two layers continues distally as the
      cleavage plane between the epineural sheaths of the trigeminal divisions and the
      dura propria of the middle fossa. This cleavage plane serves as the anatomic
      landmark for the interdural exposure of the contents of Meckel's cave. The
      superior petrosal sinus is sectioned at the medial aspect of Kawase's triangle
      and reflected along with the porus trigeminus roof. CONCLUSION: Understanding the
      critical meningeal architecture in and around Meckel's cave allows experienced
      cranial neurosurgeons to develop a subtemporal interdural approach to dumbbell
      shaped trigeminal schwannomas that effectively converts a multiple-compartment
      tumor into a single-compartment tumor. Dural incisions and stepwise mobilization
      complements our previous description of the bony dissection for this approach.

PMID- 17041498
TI  - Microsurgical approaches to the medial temporal region: an anatomical study.
AB  - OBJECTIVE: To describe the surgical anatomy of the anterior, middle, and
      posterior portions of the medial temporal region and to present an anatomic-based
      classification of the approaches to this area. METHODS: Twenty formalin-fixed,
      adult cadaveric specimens were studied. Ten brains provided measurements to
      compare different surgical strategies. Approaches were demonstrated using 10
      silicon-injected cadaveric heads. Surgical cases were used to illustrate the
      results by the different approaches. Transverse lines at the level of the
      inferior choroidal point and quadrigeminal plate were used to divide the medial
      temporal region into anterior, middle, and posterior portions. Surgical
      approaches to the medial temporal region were classified into four groups:
      superior, lateral, basal, and medial, based on the surface of the lobe through
      which the approach was directed. The approaches through the medial group were
      subdivided further into an anterior approach, the transsylvian transcisternal
      approach, and two posterior approaches, the occipital interhemispheric and
      supracerebellar transtentorial approaches. RESULTS: The anterior portion of the
      medial temporal region can be reached through the superior, lateral, and basal
      surfaces of the lobe and the anterior variant of the approach through the medial
      surface. The posterior group of approaches directed through the medial surface
      are useful for lesions located in the posterior portion. The middle part of the
      medial temporal region is the most challenging area to expose, where the approach
      must be tailored according to the nature of the lesion and its extension to other
      medial temporal areas. CONCLUSION: Each approach to medial temporal lesions has
      technical or functional drawbacks that should be considered when selecting a
      surgical treatment for a given patient. Dividing the medial temporal region into
      smaller areas allows for a more precise analysis, not only of the expected
      anatomic relationships, but also of the possible choices for the safe resection
      of the lesion. The systematization used here also provides the basis for
      selection of a combination of approaches.

PMID- 17041499
TI  - Increasing exposure of the petrous internal carotid artery for revascularization
      using the transzygomatic extended middle fossa approach: a cadaveric morphometric
      study.
AB  - OBJECTIVE: When internal carotid artery (ICA) sacrifice is planned in the
      management of difficult tumors or aneurysms at the cranial base, the petrous ICA
      may be a useful site for anastomosis for interpositional vascular bypass.
      However, exposure of the artery and performing an anastomosis in this region may
      be technically challenging because of the narrow working corridor. The authors
      describe a transzygomatic extended middle fossa approach that maximizes the
      exposure of the petrous ICA for performing the difficult anastomosis. METHODS:
      Bilateral dissections were performed on eight silicone-injected cadaveric head
      specimens. Exposure of the entire petrous ICA (horizontal segment, genu, and
      vertical segment) using the transzygomatic extended middle fossa approach was
      performed by the following steps. A frontotemporal craniotomy was performed
      followed by a zygomatic osteotomy. The temporal lobe dura was elevated
      extradurally to expose the posterior cavernous sinus and floor of the middle
      fossa. The middle fossa rhomboid was identified, which is bordered by V3
      anteriorly, the GSPN laterally, the arcuate eminence posteriorly, and the petrous
      edge medially. Bone drilling was performed in the middle fossa rhomboid and
      Glasscock's triangle with care not to violate the cochlea. The horizontal and
      vertical segments of the petrous ICA were skeletonized entirely and mobilized
      from carotid canal. The V3 segment of the trigeminal nerve was retracted
      anteriorly to obtain more distal exposure of the ICA. An osteoplastic bone flap
      of the middle fossa floor lateral to the ICA was removed to increase the working
      space. A morphometric analysis was performed, quantifying the petrous ICA
      exposure, the surgical working corridor, and the angles of exposure. RESULTS: On
      average, the length of the horizontal petrous ICA exposed was 9.2 +/- 1.0 mm
      (range, 8.0-11.0 mm). Anterior retraction of V3 provided an additional 4.3 +/-
      0.4 mm of carotid exposure (46.7% increase; P < 0.05). The length of the genu was
      on average 3.6 +/- 0.4 mm (range, 3.0-4.0 mm), and the length of the vertical
      segment of the petrous ICA was 13.1 +/- 2.0 mm (range, 10.0-15.0 mm). The average
      depth of the petrous ICA from the outer surface of the temporal bone was 30.6 +/-
      1.1 mm (range, 30.0-33.0 mm) at the V3-ICA junction and 27.2 +/- 0.7 mm (range,
      26.0-28.0 mm) at the ICA genu. The average diameter of the inner working corridor
      was 24.2 +/- 3.0 mm (range, 21.5-30.0 mm). Removal of the zygoma increased the
      outer working corridor from an average distance of 24.4 +/- 3.8 mm to 33.4 +/-
      3.4 mm (36.9% increase in exposure; P < 0.05). The average angle of exposure was
      66.5% greater (P < 0.05) with zygomatic arch removal (39.3 +/- 4.9 degrees) than
      without zygomatic arch removal (23.6 +/- 2.7 degrees). CONCLUSION: The
      transzygomatic extended middle fossa approach provides a wide surgical corridor
      for maximal exposure of the petrous ICA with minimized temporal lobe retraction.
      This large exposure facilitates vascular anastomoses at the petrous ICA and
      provides working room to maneuver instruments. The middle fossa rhomboid is a key
      landmark to identify the petrous ICA and to avoid neuro-otologic structures.

PMID- 17041500
TI  - "Target bypass": a method for preoperative targeting of a recipient artery in
      superficial temporal artery-to-middle cerebral artery anastomoses.
AB  - OBJECTIVE: To introduce a method for preoperative targeting of a proper recipient
      artery in superficial temporal artery-to-middle cerebral artery anastomosis.
      METHODS: Six operations for superficial temporal artery-to-middle cerebral artery
      anastomosis in four patients with moyamoya disease or moyamoya-like disease and
      two operations in two patients with atherosclerotic cerebrovascular occlusive
      disease accompanied by coronary artery stenosis were performed using our method.
      Before surgery, a 3-Tesla magnetic resonance imaging study was performed with
      axial T1-weighted three-dimensional magnetization-prepared rapid acquisition
      gradient-echo sequences and three-dimensional time-of-flight magnetic resonance
      angiography. Data on quantitative regional cerebral blood flow were obtained by
      iodine-123-labeled N-isopropyl-iodoamphetamine single-photon emission computed
      tomography or positron emission computed tomography. The magnetic resonance
      angiography and regional cerebral blood flow data sets were registered with the
      magnetization-prepared rapid acquisition gradient-echo data set by means of the
      coregistration function of the SPM2 software. We examined the arteries located on
      or near the cortex where the regional cerebral blood flow had significantly
      decreased and used the coregistered data set and MRIcro software to select the
      cortical artery with the largest diameter as the target recipient artery. At the
      surgery, the data sets were applied to the neuronavigation system and the actual
      site of the target was confirmed in the operation before scalp incision. The
      superficial temporal artery was anastomosed with the target through a small
      craniotomy. RESULTS: Successful bypass surgery to the target was confirmed in all
      cases. CONCLUSION: The "target bypass" method might be effective for cases with
      moyamoya disease or for cases requiring surgery through a small craniotomy.

PMID- 17041501
TI  - Treatment of giant and large internal carotid artery aneurysms with a high-flow
      replacement bypass using the excimer laser-assisted nonocclusive anastomosis
      technique.
AB  - OBJECTIVE: To define the clinical value of the high-flow replacement bypass using
      the excimer laser-assisted nonocclusive anastomosis technique in the treatment of
      patients with a noncoilable, nonclippable giant or large intracranial aneurysm of
      the internal carotid artery (ICA). METHODS: We studied 34 patients with a giant
      intracranial aneurysm of the ICA proximal to its bifurcation who were treated
      with an extracranial-intercranial high-flow replacement bypass in our hospital
      between 1999 and 2004. We retrospectively collected data for patient
      characteristics, operative aspects, complications, and functional health scores
      using the modified Rankin scale. Long-term data were updated by questionnaire and
      telephone survey. Mean long-term follow-up period was 3.3 years (range, 0.6-5.6
      yr). RESULTS: We were able to construct a patent bypass in 33 out of 34 patients
      (97%). In six patients (17%), we needed two bypass attempts. In one patient (3%),
      the bypass was technically impossible. After bypass construction, we occluded the
      ICA during or after surgery in 32 patients (94%), causing aneurysm thrombosis in
      all of these patients. A fatal complication occurred in two patients (6%) before
      we could occlude the ICA. A nonfatal complication occurred in seven patients
      (21%). In the long term, 25 patients (74%) had a favorable outcome and 27
      patients (79%) were independent (modified Rankin scale, <3). CONCLUSION: This
      study shows that the excimer laser-assisted nonocclusive anastomosis high-flow
      replacement bypass, which provides maximum brain protection because of its
      nonocclusive character, is a reliable and effective method to treat these
      otherwise untreatable patients.

PMID- 17041502
TI  - Surgical management of hypothalamic hamartomas with epilepsy: the
      stereoendoscopic approach.
AB  - OBJECTIVE: Hypothalamic hamartomas (HHs) require surgical treatment in patients
      presenting with refractory epilepsy. METHODS: The authors report on a single
      center series of 33 patients (24 males, 9 females) who underwent surgery between
      January 1997 and April 2004. They experienced several types of seizure (gelastic,
      tonic, partial, atonic, generalized tonic-clonic, dacrystic, infantile spasm,
      mental retardation, and behavioral and endocrinological abnormalities). Forty
      nine interventions were carried out. Every patient, with the exception of the
      first, underwent hamartoma disconnection (pterional approach, six patients;
      endoscopy, 15 patients; both, 11 patients). The endoscopic approach was carried
      out with a frameless stereotactic system to enhance feasibility and efficacy of
      the disconnecting procedure. RESULTS: Surgery-related neurological complications
      occurred in two patients, both after a pterional microsurgical approach.
      Furthermore, two patients experienced panhypopituitarism and one patient
      experienced transitory central insipid diabetes. All patients but one showed
      recovery or considerable improvement of their epilepsy (Engel Class 1, 48.5%;
      Engel Class 2, 3%; Engel Class 3, 45.5%; mean follow-up duration, 1 yr 7 mo).
      CONCLUSION: According to the proposed classification of sessile HH into four
      types, the best candidates for endoscopic disconnection are Type 2 and Type 3
      HHs. In the present series, 90% of patients affected by Type 2 HH became seizure
      free and the remaining 10% improved; of those with Type 3 HH at presentation,
      35.3% recovered and 60% improved. Neuropsychological and endocrinological test
      results showed improvement in many patients. Data from our series demonstrate
      that frameless stereotactic endoscopic disconnection should be considered as the
      treatment of choice in the presence of favorable anatomic conditions.

PMID- 17041503
TI  - Orthogonal interlocking tandem clipping technique for the reconstruction of
      complex middle cerebral artery aneurysms.
AB  - OBJECTIVE: Complex aneurysms arising at the middle cerebral artery (MCA)
      bifurcation frequently present a microsurgical challenge to effectively
      obliterate while maintaining patency of the distal MCA branches. These aneurysms
      are often multilobed, with their long axis aligned with the long axis of the M1
      trunk, placing the dome of the aneurysm in the surgeons' line of sight,
      preventing an unobstructed view of the entire bifurcation and proximal M1
      segment. MCA aneurysms often have a broad neck, splaying the bifurcation. An
      orthogonal interlocking tandem clipping technique, maximizing the use of
      fenestrated aneurysm clips, is presented as a means to completely obliterate the
      aneurysm and simultaneously "reconstruct" the MCA bifurcation. CLINICAL
      PRESENTATIONS AND INTERVENTION: Fifteen complex MCA aneurysms were treated using
      an interlocking tandem clipping technique. In its simplest application, the
      blades of the initial aneurysm clip are incorporated into the fenestration of the
      second clip. Obliteration of the residual aneurysm is achieved with the blades of
      the second, fenestrated clip. RESULTS: Satisfactory aneurysm obliteration and
      reconstruction of the MCA bifurcation was achieved in all cases using this
      technique, with excellent neurological outcomes. CONCLUSION: Morphologically
      complex multilobed MCA aneurysms can be effectively clipped with "reconstruction"
      of the normal vascular anatomy using a tandem interlocking clipping technique. A
      fenestrated clip is used to incorporate the blades of the initial clip, while
      obliterating the remainder of the aneurysm.

PMID- 17041504
TI  - Submandibular-infratemporal interpositional carotid artery bypass for cranial
      base tumors and giant aneurysms.
AB  - OBJECTIVE: Cerebral revascularization is an important strategy in the surgical
      management of some complex cranial base tumors and unclippable aneurysms. A high
      flow bypass may be necessary in planned carotid occlusion or sacrifice. The
      cervical-to-supraclinoid internal carotid artery bypass or cervical carotid-to
      middle cerebral artery bypass are useful procedures to bypass lesions at the base
      of the cranium. We describe technical modifications of the submandibular
      infratemporal interpositional saphenous vein (or radial artery) graft bypass
      technique specifically designed to avoid removal of the zygoma. METHODS: The
      saphenous vein or radial artery interpositional graft is tunneled through a burr
      hole created in the floor of the middle fossa via a submandibular-infratemporal
      route avoiding removal of zygoma and attachments of the masseter or temporalis
      muscles. RESULTS: The technique is demonstrated in one patient with removal of a
      malignant cavernous sinus tumor and in another patient with an unclippable giant
      carotid bifurcation aneurysm. CONCLUSION: The advantages of this approach include
      preservation of the facial anatomy and creation of a short and safe route for
      passage of the saphenous vein or radial artery graft.

PMID- 17041505
TI  - Minimally invasive transmuscular pedicle screw fixation of the thoracic and
      lumbar spine.
AB  - OBJECTIVE: This study assessed the feasibility and safety of percutaneous
      posterior pedicle screw fixation for instabilities of the thoracic and lumbar
      spine, using standard instruments designed for the open approach and fluoroscopy.
      METHODS: All patients who underwent percutaneous posterior pedicle screw fixation
      of the thoracic and lumbar spine were studied retrospectively. Charts and
      operative notes were analyzed for epidemiological data, underlying spinal
      pathological features, and indications for stabilization, stabilized segments,
      number of implanted pedicle screws, surgical time, and complications.
      Postoperative computed tomographic scans were analyzed for screw position.
      RESULTS: From May 2002 through May 2005, 115 internal fixators were implanted
      percutaneously in 104 patients. A total of 488 pedicle screws were implanted,
      stabilizing 1 to 5 spinal motion segments. Median surgical time was 93 minutes.
      On postoperative computed tomographic scans, 87% of screw positions were rated
      good, 10% were rated acceptable, and 3% were rated unacceptable. A total of 11
      revisions were necessary, 9 for misplaced screws and 2 for loosening of anchor
      bolts. Only two of the patients experienced new clinical symptoms (i.e.,
      radicular pain) because of screw misplacement. No patients experienced new
      neurological deficits or other surgery-related morbidity. CONCLUSION: This study
      shows that percutaneous internal pedicle screw fixation using standard
      instruments is feasible and safe for posterior stabilization of the thoracic and
      lumbar spine. It is a straightforward alternative for open approaches or
      minimally invasive ones using navigation in conjunction with customized
      instruments. Accuracy of screw placement is similar to that reported for other
      techniques.

PMID- 17041506
TI  - Intraoperative cortical surface characterization using laser range scanning:
      preliminary results.
AB  - OBJECTIVE: To present a novel methodology that uses a laser range scanner (LRS)
      capable of generating textured (intensity-encoded) surface descriptions of the
      brain surface for use with image-to-patient registration and improved cortical
      feature recognition during intraoperative neurosurgical navigation. METHODS: An
      LRS device was used to acquire cortical surface descriptions of eight patients
      undergoing neurosurgery for a variety of clinical presentations. Textured surface
      descriptions were generated from these intraoperative acquisitions for each
      patient. Corresponding textured surfaces were also generated from each patient's
      preoperative magnetic resonance tomograms. Each textured surface pair (LRS and
      magnetic resonance tomogram) was registered using only cortical surface
      information. Novel visualization of the combined surfaces allowed for
      registration assessment based on quantitative cortical feature alignment.
      RESULTS: Successful textured LRS surface acquisition and generation was performed
      on all eight patients. The data acquired by the LRS accurately presented the
      intraoperative surface of the cortex and the associated features within the
      surgical field-of-view. Registration results are presented as overlays of the
      intraoperative data with respect to the preoperative data and quantified by
      comparing mean distances between cortical features on the magnetic resonance
      tomogram and LRS surfaces after registration. The overlays demonstrated that
      accurate registration can be provided between the preoperative and intraoperative
      data and emphasized a potential enhancement to cortical feature recognition
      within the operating room environment. Using the best registration result from
      each clinical case, the mean feature alignment error is 1.7 +/- 0.8 mm over all
      cases. CONCLUSION: This study demonstrates clinical deployment of an LRS capable
      of generating textured surfaces of the surgical field of view. Data from the LRS
      was registered accurately to the corresponding preoperative data. Visual
      inspection of the registration results was provided by overlays that put the
      intraoperative data within the perspective of the whole brain's surface. These
      visuals can be used to more readily assess the fidelity of image-to-patient
      registration, as well as to enhance recognition of cortical features for
      assistance in comparing the neurotopography between magnetic resonance image
      volume and physical patient. In addition, the feature-rich data presented here
      provides considerable motivation for using LRS scanning to measure deformation
      during surgery.

PMID- 17041507
TI  - Axially dynamic implants for stabilization of the cervical spine.
AB  - OBJECTIVE: Subsidence is a naturally occurring process that is observed during
      aging and after spine surgery. Rigid cervical spine instrumentation is excellent
      for stabilizing the spine. These devices, however, also retard subsidence after
      surgery. Thus, the implant carries much of the axial load, rather than sharing
      the axial load with the bone graft. This results in an increased incidence of
      construct failures, pseudoarthrosis, or both, which often occur late in the
      postoperative course. METHODS: In contrast, dynamic implants allow normal
      (natural) subsidence to occur, while effectively stabilizing the spine by
      preventing translation, rotation, and angular deformation. Load sharing, which
      works with, instead of against, the normal biology of bone healing, occurs with
      axially dynamic implants, resulting in more robust and earlier fusions. RESULTS:
      Diminished incidences of construct failures have been reported with dynamic
      implants. CONCLUSION: Dynamic implants seem to be the system of choice for
      ventral cervical stabilization in selected patients.

PMID- 17041508
TI  - Surgical pitfalls of an ultrasonic bone curette (SONOPET) in spinal surgery.
AB  - OBJECTIVE: We report our experience with the SONOPET ultrasonic bone curette.
      METHODS: Between September 2001 and July 2005, 546 patients underwent microscopic
      spinal surgeries using a high-speed drill and the SONOPET instrument. RESULTS: We
      encountered operative complications thought to be attributable to the use of the
      SONOPET in six patients (1.1%). There were five instances of dural puncture and
      one spinal cord injury. All dural tears occurred when the dura mater was
      aspirated into the tip of the SONOPET. None of the affected patients developed
      postoperative clinical complications because cerebrospinal fluid leakage was
      avoided by appropriate closure. We think that the transient spinal cord injury
      occurred because the vibration emanating from the SONOPET was transmitted
      directly to the spinal cord. Some patients experienced damage to the epidural
      venous plexus for reasons similar to those described above. CONCLUSION: SONOPET
      facilitates the removal of bone in a narrow field, such as that encountered
      during keyhole surgery. It aids in the removal of the lateral edge of bone and is
      especially useful for expanding the foramen intervertebrale or opening the
      lateral recess. However, its use is not without risk. To prevent dural tears and
      venous plexus injury, we recommend that cotton be placed between the SONOPET and
      important structures. To avoid spinal cord injury, we suggest that the SONOPET be
      inserted horizontal with the dura mater to avoid the direct transmission of
      vibrations emanating from the instrument to the spinal cord. SONOPET is suitable
      for decompression on the lateral side, but not for decompression above the spinal
      cord.

PMID- 17041509
TI  - Frameless stereotactic cannulation of the foramen ovale for ablative treatment of
      trigeminal neuralgia.
AB  - OBJECTIVE: Ablative neurosurgical treatment of trigeminal neuralgia, including
      percutaneous radiofrequency thermocoagulation, requires cannulation of the
      foramen ovale. To maximize patient security and cannulation success, a frameless
      stereotactic system was evaluated in a phantom study, a cadaveric study, and a
      preliminary clinical trial. METHODS: Frameless stereotaxy using an optical
      navigation system, an aiming device, and a noninvasive vacuum mouthpiece-based
      registration and patient fixation technique was used for the targeting of a test
      body based on 1-, 3-, and 5-mm axial computed tomographic slices and of the
      foramen ovale in three cadavers and 15 patients based on 3-mm axial computed
      tomographic slices. RESULTS: The mean normal (x/y) localization accuracy/standard
      deviation (n = 360) was 1.31/0.67 mm (1-mm slices), 1.38/0.65 mm (3-mm slices),
      and 1.84/0.96 mm (5-mm slices). Significantly better results were achieved with 1
      and 3-mm slices when compared with 5-mm slices (P < 0.001). The foramen ovale (3
      x 6 mm) was successfully cannulated at the first attempt in all cadavers and
      patients, which indicates clinical localization accuracies better than 1.5 mm in
      the anteroposterior and 3 mm in the medial-lateral directions. CONCLUSION: Based
      on the noninvasive Vogele-Bale-Hohner vacuum mouthpiece, there is no need for
      invasive head clamp fixation. Imaging, real laboratory simulation, and the actual
      surgical intervention can be separated in time and location. The presented data
      suggest that frameless stereotaxy is a predictable and reproducible procedure,
      which may enhance patient security and cannulation success independent of the
      surgeon's experience.

PMID- 17041510
TI  - Recanalization of obstructed cerebrospinal fluid ventricular catheters using
      ultrasonic cavitation.
AB  - OBJECTIVE: Fifty percent of implanted cerebrospinal fluid (CSF) shunts fail
      within 2 years, primarily because of obstruction of the proximal catheter.
      Percutaneous techniques to reduce the morbidity of shunt revision are being
      developed. The authors describe the development of a device that uses ultrasonic
      cavitation to unblock ventricular catheters. METHODS: In collaboration with
      Cybersonics, Inc. (Erie, PA), we designed, built, and tested a system that
      produces low-frequency ultrasound (20-28 kHz). Extensional ultrasonic waves are
      transmitted along a tapered wire (final diameter, approximately 0.8 mm) to the
      tip, where cavitation is produced in a highly localized region. An in vitro model
      of sheep choroid plexus occluding typical ventricular catheters was developed.
      The device was safety tested in vivo in rat and pig brains by introducing the
      device into shunt catheters inserted during simulated shunt surgery. A clinical
      safety trial using the device to attempt to remove blocked and adherent
      ventricular catheters has commenced. RESULTS: In the sheep choroid plexus model,
      at least 90% of the occluded holes were unblocked in a few minutes, restoring
      normal flow. There was no adverse effect of the device within shunt catheters
      inserted into live animal brains. Four patients have undergone treatment with the
      device at open CSF shunt surgery without adverse effect, and the device seems
      effective at unblocking and freeing the occluded catheters. CONCLUSION:
      Ultrasonic cavitation produced at the end of a fine wire that is introduced
      percutaneously into a CSF shunt promises to be a useful technique for minimally
      invasive proximal ventricular CSF shunt catheter revision.

PMID- 17041511
TI  - Electrocautery-induced ignition of spark showers and self-sustained combustion of
      onyx ethylene-vinyl alcohol copolymer.
AB  - OBJECTIVE: Ethylene-vinyl alcohol copolymer mixed with micronized tantalum (Ta)
      as radiopacifier (Onyx; Micro Therapeutics Inc., Irvine, CA) has emerged as a
      useful liquid embolic agent for vascular malformations. We describe
      intraoperative ignition of Onyx-embolized tissue and undertake an in vitro
      investigation to reproduce and characterize this hazard. METHODS: Samples of
      Onyx, Ta-depleted Onyx, Ta-n-butylcyanoacrylate (Ta-NBCA), and Ta powder were
      exposed to monopolar and bipolar electrocautery in cut and coagulation modes at
      different power settings to reproduce the intraoperative findings. Recordings of
      sparking and combustion events were analyzed to characterize duration and
      relative frequency. RESULTS: Spark showers and self-sustained combustion were
      observed intraoperatively when an Onyx-embolized artery was coagulated with the
      monopolar electrocautery. Sparking covered a radius greater than 10 cm, and
      combustion lasted a median of 1.65 seconds (range, 0.3-12.3 s). Sparking and
      sustained combustion were reproduced in vitro by both cut and coagulation
      monopolar modes in Onyx casts and free Ta powder but not in samples of Ta
      depleted Onyx or casts of Ta-NBCA. Ignition was similarly observed when using
      bipolar electrocautery but only at higher energy settings. CONCLUSION:
      Electrocautery use on tissue containing Onyx results in potentially dangerous
      uncontrolled sparking and combustion in a process that is Ta dependent. It is
      recommended that Ta-NBCA be used instead of Onyx in situations mandating the use
      of a liquid embolic and high-energy electrocautery, pending the development of a
      safer radiopacifier for use with ethylene-vinyl alcohol copolymer.

PMID- 17041512
TI  - Hemorrhagic complications of external ventricular drainage.
AB  - OBJECTIVE: Despite the widespread use of external ventricular drainage (EVD), the
      frequency of associated hemorrhagic complications remains unclear. This
      retrospective study examined the frequency of hemorrhagic complications of EVD
      and attempted to discern associated risk factors. METHODS: Treatment records from
      160 patients admitted during a 2.5-year period who required EVD placement were
      reviewed. Indications for placement of EVD included acute complications of
      cerebrovascular disease (n = 94), traumatic brain injury (n = 36), primary
      hydrocephalus (n = 16), and tumor (n = 14). Patients received either a 3.0 or 2.5
      mm outer diameter ventricular catheter (n = 82 and 78, respectively).
      Postinsertion computed tomographic scans were obtained within 24 hours on all
      patients and were analyzed for any new hemorrhage related to the ventricular
      catheter. Patient age, sex, catheter type, and dimensions of hemorrhage were also
      analyzed. RESULTS: The incidence of EVD-related hemorrhage was 33 +/- 0.04%.
      However, the incidence of detectable change in the clinical neurological
      examination was 2.5%. A significant proportion of EVD-related hemorrhages were
      small (<4 cm), punctate, intraparenchymal hematomas. Patients with
      cerebrovascular disease exhibited an increased incidence (39%) of hemorrhage. The
      mean volume of intraparenchymal hemorrhage was larger in patients who received
      the 2.5-mm ventricular catheter, as well as those admitted for cerebrovascular
      disease. CONCLUSION: Hemorrhagic complications of EVD placement are more common
      than previously suspected. Admitting diagnosis seems to have an effect on the
      development of an associated hemorrhage and its size. Catheter gauge has an
      effect on hematoma volume. Most of the hemorrhages seen on postinsertion computed
      tomographic scans do not cause detectable changes in the clinical examination.

PMID- 17041513
TI  - Extended bifrontal craniotomy for midline anterior fossa meningiomas:
      minimization of retraction-related edema and surgical outcomes.
AB  - OBJECTIVE: Meningiomas of the anterior cranial base can be approached with a
      variety of techniques. The extended bifrontal approach is often thought to be
      associated with increased morbidity because of the need for extensive removal of
      the bone and longer surgical times. The authors have attempted to quantitate
      retraction-related edema occurring after surgery to determine whether the extra
      bone removal limits retraction and reduces the chance of brain injury. METHODS:
      Charts were reviewed for patients who underwent extended bifrontal craniotomies
      performed for meningiomas at the University of California, San Francisco, between
      1997 and 2005. Magnetic resonance imaging scans obtained before and after surgery
      were reviewed for brain edema as indicated by fluid-attenuated inversion
      recovery/T2 abnormality and grouped into four categories: A, no edema; B, edema
      restricted to the gyrus rectus; C, edema beyond the gyrus rectus; and D,
      extensive bifrontal edema. RESULTS: Forty-five patients were identified. Fifty
      four percent of patients had tumors with a diameter of more than 4 cm. Simpson
      Grade 2 or 3 resection was achieved in 82% of patients, and the average operative
      time was 12.3 hours. Vision outcome was favorable in 74% of patients. Extent of
      fluid-attenuated inversion recovery abnormality remained unchanged in 87.5%, with
      91% of patients in categories A or B edema remaining in those categories after
      surgery. There were no infections and there were two cerebrospinal fluid leaks.
      CONCLUSION: The extended bifrontal approach is a safe surgical procedure with
      limited morbidity that the authors think: 1) prevents secondary brain injury from
      excessive retraction; 2) offers great flexibility of view for the surgeon; and 3)
      should be considered the preferred approach compared with the standard bifrontal
      craniotomy for large tumors of the anterior cranial base.

PMID- 17041514
TI  - Risk of damage to the endolymphatic sac and duct during removal of the posterior
      meatal wall: an anatomic study.
AB  - OBJECTIVE: With removal of the posterior meatal wall for intrameatal acoustic
      neurinoma, preservation of the structures adjacent to the internal acoustic
      meatus is important. The authors performed an anatomic study to clarify the risk
      of damage to the endolymphatic sac and endolymphatic duct during this maneuver.
      METHODS: Twenty-seven sides of adult temporal bone were examined. Distances
      measured were between the posterior meatal lip and the upper limit of the
      endolymphatic ledge, at the upper extent of the endolymphatic sac, and between a
      reference line extending from the inferior margin of the internal acoustic meatus
      posteriorly (parallel to the petrous ridge), simulating the inferior margin of
      the drilling, and the upper limit of the endolymphatic ledge. Whether the latter
      was located on or above the line was also recorded. After posterior meatal wall
      drilling, the distance between the posterior meatal lip and the vestibular
      aqueduct surrounding the endolymphatic duct and the depth of the structure from
      the surface were assessed. RESULTS: The shortest distances between the posterior
      meatal lip and the endolymphatic ledge and between the posterior meatal lip and
      the vestibular aqueduct were 6.80 mm and 4.68 mm, respectively. The upper limit
      of the endolymphatic ledge was present on or above the reference line in
      approximately half of the specimens. CONCLUSION: During surgical maneuvers to
      remove the posterior meatal wall, the occasional close proximity of the
      endolymphatic sac and endolymphatic duct to the internal acoustic meatus should
      be kept in mind. Preoperative radiological evaluation of anatomic relationships
      is mandatory when preservation of hearing is the aim.

PMID- 17041515
TI  - Complication avoidance in peripheral nerve surgery: preoperative evaluation of
      nerve injuries and brachial plexus exploration--part 1.
AB  - Complication avoidance during peripheral nerve surgery has received little
      attention in the neurosurgical literature. The goal of our two-part review is to
      discuss these possible complications, with this initial article highlighting the
      pitfalls associated with pre- and intraoperative assessment of nerve injuries, as
      well as the operative nuances used during brachial plexus exploration to minimize
      complications.

PMID- 17041516
TI  - Complication avoidance in peripheral nerve surgery: injuries, entrapments, and
      tumors of the extremities--part 2.
AB  - The goal of this two-part review is to discuss peripheral nerve surgery
      complications, along with the techniques and principles used to prevent them. In
      this second article, we concentrate on injuries, tumors, and entrapment of nerves
      in the extremities, including carpal tunnel syndrome and ulnar nerve compression
      at the elbow.

PMID- 17041517
TI  - A method for calculating the exact angle required during pedicle subtraction
      osteotomy for fixed sagittal deformity: comparison with the trigonometric method.
AB  - OBJECTIVE: Pedicle subtraction osteotomy (PSO) has emerged as a powerful
      procedure for correcting fixed sagittal deformity. There has only been one
      attempt to quantify the magnitude of correction needed to restore sagittal
      balance; the trigonometric method for calculating the desired PSO angle is an
      approximation. We propose a method for calculating the exact angle required for
      PSO and explore how this angle differs from that obtained via the trigonometric
      method in illustrative cases. METHODS: We conducted a mathematical analysis of
      the spine with application in illustrative cases. The trigonometric method
      calculates the necessary angular correction at the axial level of the PSO, but
      along the sacral vertical line. However, the angular measurement should take
      place at the true axis of rotation, the apex of the PSO. Measurements were taken
      from full-length standing x-rays, and both methods were explored. RESULTS: The
      trigonometric method for calculating PSO angle is an exact measurement only if
      the apex of the PSO site lies on the sacral vertical line. As the apex of the PSO
      site moves anterior to that line, the trigonometric approximation underestimates
      the actual angle. As the apex of the PSO moves posterior to that line, the
      trigonometric approximation overestimates the actual angle. CONCLUSION: The
      trigonometric method for calculating the PSO angle required for surgical
      deformity correction is an approximation, but its validity in clinical practice
      was confirmed by this study. The exact angle is obtained by a method centered on
      the apex of the PSO site. Although the difference between these angles is small,
      it is an important conceptual point for spine surgeons. Measurement of the exact
      angle is easily performed and should replace the trigonometric method for
      calculating the required PSO angle when standard digital measurement tools are
      available.

PMID- 17041518
TI  - 2-Hexyl cyanoacrylate (neuracryl M) embolization of cerebral arteriovenous
      malformations.
AB  - OBJECTIVE: Neuracryl M is a newly designed liquid embolic agent. In an attempt to
      verify the safety and efficacy of neuracryl M, we participated in the PROVASIS
      Trial, a pilot study using this agent in the preoperative treatment of cerebral
      arteriovenous malformations (AVMs). Because the trial was prematurely terminated
      by the sponsoring company because of financial considerations, we now present our
      data as a single center series. METHODS: Between November 2002 and December 2003,
      six patients were enrolled in the PROVASIS trial at our institution, and four of
      these patients were randomized to treatment with neuracryl M. The patients were a
      30-year-old man with a right frontal lobe AVM, a 20-year-old man with a right
      cerebellar AVM, a 26-year-old woman with a midline cerebellar AVM, and a 47-year
      old man with a left parietotemporal lobe AVM. All patients underwent AVM
      embolization with neuracryl M, followed by definitive treatment, either open
      surgery or radiosurgery. RESULTS: In each case, there were no permanent
      complications, and blood loss was minimal. Follow-up imaging demonstrated either
      complete AVM obliteration (open surgery) or substantial diminution in AVM size
      (radiosurgery). CONCLUSION: Our data provide preliminary evidence supporting the
      thesis that neuracryl M is a safe and effective liquid embolic agent for the
      preoperative embolization of cerebral AVMs. Larger trials and continued
      experience using this novel liquid embolic agent are warranted.

PMID- 17041519
TI  - Intratumoral hydrogen peroxide injection during meningioma resection.
AB  - OBJECTIVE: Meningiomas, although histologically benign, pose a particular
      challenge to the neurosurgeon because of their extensive and exuberant
      vascularity. They often bleed extensively during resection until separated from
      their blood supply. There are a wide variety of hemostatic agents available to
      the neurosurgeon. Most of these means of hemostasis involve some sort of
      chemical, electrical, or compressive action. Although anecdotally known to be
      useful, the use of hydrogen peroxide as an intracranial hemostatic agent in
      meningioma surgery has not been formally reported. We report a technique of
      meningioma resection that uses intratumoral hydrogen peroxide injection, reducing
      the potential for blood loss and shortening resection times. METHODS: Seventy
      five patients underwent resection of a meningioma using the direct intratumoral
      H2O2 injection technique. The locations of these meningiomas included convexity
      and cranial-based lesions. None of the patients underwent preoperative
      endovascular embolization. RESULTS: The use of this technique greatly facilitated
      the removal of these tumors. No evidence of air embolism occurred during Doppler
      surveillance and no other significant side effects attributable to H2O2
      application were observed. CONCLUSION: We demonstrate a previously unreported
      technique of meningioma resection that uses direct intratumoral hydrogen peroxide
      injection, potentially reducing blood loss, shortening resection times, and
      obviating the need for preoperative embolization.

PMID- 17041520
TI  - Stent placement for intracranial cysts by combined stereotactic/endoscopic
      surgery.
AB  - OBJECTIVE: The treatment of space-occupying cystic lesions includes percutaneous
      cyst aspiration, marsupialization, percutaneous ventriculocystotomy, or Rickham
      catheter implantation. In some patients, the cysts tend to recur and repeated
      evacuations are necessary. The authors present a new treatment method with
      internal drainage of cysts into the ventricular system using a balloon-mounted
      vascular stent. METHODS: Six patients with cysts of low-grade gliomas, one with
      monocystic craniopharyngioma, and one with suprasellar arachnoid cyst were
      treated between September 2003 and May 2005. All patients were symptomatic after
      multiple previous treatments. Stent implantations were performed under local
      anesthesia in adults and under general anesthesia in children. In all patients,
      the stereotactic frame and computed tomographic and magnetic resonance fusion
      were used for an optimized approach. The treatment was performed in a
      compassionate manner and the patients were informed about the off-label use of
      the device. RESULTS: Stent placement was successful in all eight patients without
      procedure-related complications. Improvement of clinical symptoms was seen in
      seven out of eight patients. Seven out of eight cysts decreased in size within a
      follow-up period of up to 23 months (mean, 17 mo; median, 18 mo; range, 6-23 mo).
      The first patient showed recurrence of the tumor cyst 3 months after initial
      treatment with a Herkulink stent (5 x 18 mm), followed by retreatment with an
      Omnilink stent (6 x 28 mm; Guidant Corp., Santa Clara, CA). Stenting was
      ineffective in one patient. CONCLUSION: Treatment of intracranial cystic lesions
      by internal drainage is possible with the use of stent-assisted
      ventriculocystostomy.

PMID- 17041521
TI  - Intravascular ultrasound for intracranial angioplasty and stent placement:
      technical case report.
AB  - OBJECTIVE: Intravascular ultrasound (IVUS) imaging has been used extensively in
      coronary artery interventions and has provided invaluable information for the
      understanding and treatment of coronary arterial disease. We present here the
      first description, to our knowledge, of IVUS-guided intracranial arterial
      interventions in the clinical setting. CLINICAL PRESENTATION: Two patients
      underwent intracranial angioplasty and stent placement with the assistance of
      IVUS for the evaluation of their lesions. One patient underwent stenting to treat
      an occlusive dissection of the left internal carotid artery that occurred during
      arteriovenous malformation embolization. Another patient underwent angioplasty
      and stenting for high-grade restenosis of a basilar artery atherosclerotic
      lesion. RESULTS: Both patients underwent successful revascularization procedures.
      The patient with the dissection had a small intraventricular and parenchymal
      hemorrhage documented by computed tomography 4 hours after treatment, but did not
      develop hydrocephalus or further hemorrhage. Both patients did well clinically
      and had no permanent neurological deficits. IVUS provided important information
      in terms of lesion evaluation, stent selection, and stent placement in each case.
      CONCLUSION: IVUS of the intracranial circulation may assist the performance of
      intracranial angioplasty and stenting. It provides useful information that can
      affect clinical decisions. It may prove to be a valuable tool in clinical use and
      enhance our understanding of vascular disease of the intracranial circulation, as
      it has in the coronary circulation.

PMID- 17041522
TI  - Coating the wall of an injured intracranial carotid artery during tumor removal
      with n-butyl-2-cyanoacrylate: technical case report.
AB  - OBJECTIVE: Carotid artery injury close to the clinoid process is difficult to
      repair, and is even more so when the vessel is firmly attached to a calcified
      tumor. We treated a patient with an intraoperative carotid lesion by coating the
      vessel wall with n-butyl-2-cyanoacrylate (NBCA). CLINICAL PRESENTATION: A 7-year
      old boy was referred to our clinic with a 3-month history of somnolence, apathy,
      and headache. Neurological examination revealed bitemporal hemianopsia. The
      cranial magnetic resonance imaging and computed tomographic scans showed a sellar
      and suprasellar calcified mass with heterogeneous contrast enhancement, a cyst
      component in the upper part of the tumor displaced upward and back from the
      mesencephalic and diencephalic structures. INTERVENTION: The patient underwent a
      pterional craniotomy. Using a microsurgical technique, the suprasellar part of
      the craniopharyngioma was removed. In an attempt to dissect the calcified mass
      from the carotid artery on the right side, the vessel was unintentionally
      injured, followed by severe bleeding. Temporary occlusion and suturing of the
      vessel was impossible because of the overlying hard mass. To avoid a permanent
      occlusion, we decided to coat the injured artery wall with 100% NBCA. For this,
      0.5 ml of NBCA was distributed on the surface of the injured segment and
      surrounding subarachnoid space by injection through a needle. An excellent
      hemostasis could be obtained immediately after coating. The patient woke up with
      no new neurological deficits. A digital cerebral angiogram obtained a few days
      after the procedure did not show vasospasm, stenosis, or pseudoaneurysm in the
      supraclinoidal segment of the carotid artery. A magnetic resonance angiogram
      obtained 3 years later showed a normal shape of the internal carotid artery and a
      stable residual tumor without inflammatory signs. The child is now attending
      school and is under hormonal therapy. CONCLUSION: For hemostatic purposes, the
      technique of coating an injured arterial wall with NBCA may be useful in cases in
      which a microsuture is impossible and a permanent artery occlusion is unwanted
      because of a risk of an ischemic stroke. It could serve as a transitory measure
      until a microsurgical bypass or the balloon test occlusion tolerance allow the
      trapping of the affected artery.

PMID- 17041523
TI  - An oblique paraspinal approach for intracanalicular disc herniations of the upper
      lumbar spine: technical case report.
AB  - OBJECTIVE: To present our experience of treating the central or paramedian disc
      herniations of the upper lumbar levels through a paraspinal approach. CLINICAL
      PRESENTATION: We present four patients with intracanalicular disc herniations at
      the L1-L2 or L2-L3 level. All patients had unilateral or bilateral radicular leg
      pain and motor weakness. TECHNIQUE: Considering the unique characteristics of the
      upper lumbar spine, we performed the oblique paraspinal approach to expose the
      central portion of disc and removed the herniated disc effectively.
      Postoperatively, their symptoms were improved. There was no instability during
      the follow-up period. CONCLUSION: The oblique paraspinal approach for the
      treatment of central disc herniations at the upper lumbar levels is an effective
      nonfusion technique that preserves most of the facet joint and provides a wide
      surgical field.

PMID- 17041524
TI  - Endoscope-assisted microvascular decompression for trigeminal neuralgia:
      technical case report.
AB  - OBJECTIVE: Microvascular decompression may fail to relieve trigeminal neuralgia
      because a compressing vessel at the root entry zone may be overlooked during
      surgery. Alternatively, effective decompression may not always be achieved with
      the visualization provided by the microscope alone. We theorized that the
      addition of an endoscope would improve the efficacy of microvascular
      decompression. METHODS: We retrospectively reviewed microvascular decompression
      of the trigeminal nerve in 114 patients. Before closure, the endoscope was used
      to inspect the root entry zone. When visualization with the microscope was poor,
      the endoscope was used to identify an aberrant vessel and to perform or improve
      the subsequent decompression. RESULTS: Of 114 patients who underwent
      microvascular decompression, 113 successfully underwent endoscopy. In 38 patients
      (33%), endoscopy revealed arteries that were poorly seen (25%) or not seen at all
      (8%) with the microscope. At a mean follow-up period of 29 months, the pain was
      completely relieved in 112 patients (99.1%), all of whom were off medication.
      Complications included trigeminal dysesthesias in nine patients and a wound
      infection, partial hearing loss, and complete hearing loss in one patient each.
      The overall complication rate was 9%. CONCLUSION: Endoscopy is a simple and safe
      adjunct to microscopic exploration of the trigeminal nerve. The markedly improved
      visualization increases the likelihood of identifying the offending vessel and
      consequently of achieving satisfactory decompression of the nerve. Thus far, the
      success rate has been high, and the complication profile is comparable to that of
      other large series.

PMID- 17041525
TI  - Unruptured intracranial aneurysms: the unreliability of clinical judgment, the
      necessity for evidence, and reasons to participate in a randomized trial.

PMID- 17041526
TI  - [Diffusion and perfusion MR imaging in cerebral lymphomas].
AB  - Because of the increasing incidence of cerebral lymphoma, it is critical for
      patient management to recognize the MR features of this disease. We present the
      characteristic morphological and functional MRI features of this tumor. The
      findings on MRI studies, including morphological, diffusion and perfusion
      imaging, performed in 9 biopsy-proven cases of cerebral lymphoma with 13 lesions
      are presented and analyzed, and are discussed in comparison with published
      literature data. All patients underwent diffusion-weighted imaging with a single
      shot echo-planar pulse sequence. Dynamic susceptibility-contrast MRI was
      performed using a T2*-weighted gradient-echo echo-planar sequence after
      intravenous injection of chelates of gadolinium at the rate of 6 ml/s and a
      temporal resolution of 1 second. All cases of cerebral lymphoma appeared
      hypointense or isointense on T1-weighted images and in 75% of cases iso- or
      hypointense on T2-weighted images. All lesions enhanced except one in a patient
      receiving steroid therapy. On diffusion-weighted images, tumours were
      hyperintense with normal or decreased ADC values (0.717+/-0.152.10-3 mm2/sec,
      range: 0.550-1.014) and an ADC ratio tumour/normal white matter of 0.974+/-0.190
      (range: 0.768-1.410). On perfusion, the signal intensity-time curve of each
      tumour showed a characteristic type of curve with a significant increase of the
      signal intensity above the baseline and a low maximum relative cerebral blood
      volume ratio (rCVBmax) of 1.43+/-0.64 (0.55-2.62). Due to their higher
      cellularity, the lack of neoangiogenesis, and the increased permeability of the
      blood-brain barrier related to the infiltration of blood vessels wall by
      lymphomatous cells, cerebral lymphoma presents characteristic diffusion and
      perfusion MRI features that should be useful for diagnosis and patient follow-up.

PMID- 17041527
TI  - Reversible splenial lesion with restricted diffusion in a wide spectrum of
      diseases and conditions.
AB  - OBJECTIVE: Reversible lesion in the central area of the splenium of the corpus
      callosum (SCC) is a unique phenomenon occurring particularly in patients with
      encephalitis or encephalopathy and in patients receiving antiepileptic drugs
      (AED). We report MR imaging findings, clinical courses, and outcomes in eight
      patients with various diseases and conditions. MATERIALS AND METHODS: Eight
      patients with a reversible SCC lesion with transiently restricted diffusion were
      reviewed retrospectively. Diseases and conditions that were associated with a
      reversible lesion included epilepsy receiving AED (n=1), seizure from eclampsia
      receiving AED (n=1), mild infectious encephalitis (n=2), hypernatremia resulting
      in osmotic myelinolysis (n=1), and neoplasm (n=3) such as acute lymphocytic
      leukemia, spinal meningeal melanocytoma, and esophageal cancer. We evaluated MR
      imaging findings and clinical findings. RESULTS: Seven patients had isolated SCC
      lesions; one patient with osmotic myelinolysis showed additional parenchymal
      lesions. The reversible SCC lesion shape was oval (n=6) or extended (n=2). The
      mean apparent diffusion coefficient value of the splenial lesion was 0.40+/-0.16
      x 10-3 mm2/s, ranging from 0.22 to 0.64 x 10-3 mm2/s. In a patient with osmotic
      myelinolysis, additional white matter lesions, shown as restricted diffusion,
      were revealed as not reversible on follow-up MR imaging. Neurological courses and
      outcomes were good in seven patients with isolated SCC lesions, but poor in one
      with osmotic myelinolysis. CONCLUSION: Reversible SCC lesion with restricted
      diffusion is apparent in a wide spectrum of diseases and conditions. Neurological
      courses and outcomes are good, particularly in patients with isolated SCC
      lesions. Knowledge of MR imaging findings and the associated spectrum of diseases
      and conditions might prevent unnecessary invasive examinations and treatments.

PMID- 17041528
TI  - Facial malignant peripheral nerve sheath tumors.
AB  - BACKGROUND/PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are rare
      neoplasms, only sporadically reported involving the maxillo-mandibular region
      (ten cases with CT or MR data). We present here five additional cases with CT and
      MR findings along with an extensive review of the literature. RESULTS: Accurate
      diagnosis of MPNSTs is difficult because pathological like radiological criteria
      are often non specific. Radiological features display a large spectrum of
      abnormalities from a well-delineated heterogeneous appearance simulating benign
      schwannoma to extensive erosive patterns. Their development along the mandibular
      nerve, the absence of any target or central dot sign, their strong predominant
      peripheral enhancement must suggest the diagnosis of MPNSTs while irregular bone
      destruction or the detection of poorly defined margins with muscular infiltration
      are the most reliable criteria of malignancy. Unfortunately, MPNSTs also display
      a considerably varied histology. Careful clinical and radiological correlation
      should bring pathologists to examining large samples of the lesion to better
      evaluate the overall organisation of the lesion and detect some evocative
      criteria often only present in some areas of the sample as the peculiar curlicue
      or whorled arrangement of the spindle cells or the alternation of densely
      cellular fascicles with hypocellular, myxoid zones. Focal, limited immunostaining
      for S-100 protein is one of the most important additional criterion. CONCLUSION:
      If accurate early diagnosis often remains difficult, careful correlation of
      clinical, pathological and radiological data should in most cases suggest a
      diagnosis of MPNSTs which display a poor prognosis and requires early and adapted
      treatment.

PMID- 17041529
TI  - [MRI findings in neuro-Behcet's disease].
AB  - PURPOSE: Describe the patterns and location of lesions seen on MR imaging in
      neuro-Behcet's disease. OBSERVATIONS: 33 patients with neuro-Behcet's disease
      (mean age: 27 years) imaged by MRI were reviewed. Most common neurologic symptoms
      included headaches and pyramidal signs. MRI examinations (Siemens Magnetom Impact
      1 Tesla) included the following sequences: T1wi, T2wi, Flair, MPR-3D and MRA
      sequences. RESULTS: Parenchymal lesions were identified in 21 patients.
      Brainstem, internal capsule, cerebral white matter, basal ganglia were involved
      respectively in 14, 10, 7, and 5 cases. Vascular thrombosis (venous: n=7;
      arterial: n=1) were observed in eight. MRI was normal in four patients.
      CONCLUSION: This study shows the value of MR imaging for the exploration of
      parenchymal lesions of neuro-Behcet's and confirms the frequency of brainstem
      involvement.

PMID- 17041531
TI  - Massive stroke in a patient with pituitary apoplexy, cervical carotid artery
      stenosis and hypotension.
AB  - We report a case of massive cerebral infarct in the early stage of pituitary
      apoplexy. The case is unique because the stroke was delayed and occurred only
      after the patient developed severe arterial hypotension superimposed on a tandem
      internal carotid artery stenosis by both the sellar mass on the siphon and an
      unknown homolateral atheromatous cervical lesion. Illustrated with MRI and
      specifically by diffusion-weighted imaging, this case reinforces the idea that a
      low apparent diffusion coefficient in a non-enhancing sellar mass may indicate
      the presence of pituitary apoplexy and help in the early adequate management of
      such patients.

PMID- 17041530
TI  - Hyperselective intra-arterial preoperative chemotherapy in patients with squamous
      cell carcinoma of the oral cavity: preliminary results.
AB  - OBJECTIVES: To investigate radiological response and findings after Intra
      Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of
      the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC.
      Radiological assessment was performed on day 7 and day 21 after each cycle using
      CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60;
      male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary
      tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM
      classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients
      had good locoregional/systemic tolerance and 3 showed clinical objective response
      (OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and
      1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI,
      1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD
      on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable
      patients. Two patients presented intratumoral necrosis and 5 patients displayed
      local edema (MRI). One patient had modification of the sternocleidomastoid muscle
      after IAC. CONCLUSION: Radiological modifications were observed in the infused
      area and correlated well with clinical response. This study is ongoing.

PMID- 17041532
TI  - Bilateral wallerian degeneration of the middle cerebellar peduncles due to
      unilateral pontine infarction.
AB  - We report the case of a patient with bilateral and symmetrical T2
      hyperintensities of the middle cerebellar peduncles. She had a history of left
      pontine infarction 8 months before. This was attributed to bilateral Wallerian
      degeneration. MR Spectroscopy showed decreased N-acetyl aspartate/Creatine
      (NAA/Cr) ratio in the cerebellar peduncles as well as in the whole cerebellum. We
      hypothesize that this could reflect neuronal degeneration following a stroke.

PMID- 17041533
TI  - [Imaging follow-up of post-traumatic myelomalacia].
AB  - The authors report a case of secondary worsening of neurological symptoms in a
      patient 2 months after cord injury at T5 causing paraplegia. The MRI showed
      myeolomalacia, which appears as cord oedema, located in the grey matter,
      extending increasingly from the initial lesion (eighth thoracic vertebra) to the
      bulb. This cord lesion known as grey matter cytotoxic oedema, evolved into a
      syringomyelic cavity.

PMID- 17041534
TI  - Intracerebral epidermoid tumor: pathogenesis of intraparenchymal location and
      magnetic resonance imaging findings.

PMID- 17041535
TI  - Malignant oculomotor schwannoma: diffusion MR imaging.

PMID- 17041536
TI  - Endovascular treatment of ruptured intracranial aneurysms: immediate result and
      long term follow up.

PMID- 17041537
TI  - [Neurosarcoidosis as the initial presentation of systemic sarcoidosis].

PMID- 17041538
TI  - The abnormally dilated internal auditory canal: a non-specific finding or a
      distinctive pathologic entity.

PMID- 17041539
TI  - Comparison of multidetector row CT cross-sectional source images with multiplanar
      2D-, 3D- reconstructions and virtual endoscopy in assessment of the middle ear.

PMID- 17041540
TI  - [Atypical location of a solitary fibrous tumor in the fourth ventricle].

PMID- 17041542
TI  - Granular cells tumour in the oral cavity: report of eleven cases treated with
      laser surgery.
AB  - AIM: The aim of this paper is to examine the clinical and histological feature of
      oral tumours of neural derivation and discuss their treatment. METHODS: Between
      1999 and 2004, 11 patients (6 females, 5 males; age range 28-66 years) were
      treated for tumours classified as being of neural origin; they were all
      myoblastomas or granular cells tumours (ex Abrikossoff tumour). Eight were
      located on the dorsum of the tongue, 2 on the lateral margin and 1 on the right
      buccal mucosa. In all cases the mass appeared nodular, single and firm; patients
      were treated in a single session by excisional resection with 808 and 830 diode
      laser. RESULTS: During follow-up, which ranged from 5 months to 5 years, there
      was no indication of tumour recurrence. Histopathological analysis of
      haematoxylin and eosinstained sections showed all specimens to exhibit features
      typical of GCT; 6 tumours were well circumscribed, whereas 5 infiltrated adjacent
      connective tissue, muscle fibres and nerve bundles. In 10 of the 11 cases, the
      immunohistochemical S-100 protein stain was available and appeared positive.
      Pseudo-epitheliomatous hyperplasia of different degrees was present in 5
      patients, along the overlying epithelium. CONCLUSIONS: Granular cell tumour is a
      benign neoplasm with a tendency to relapse if not completely removed. The
      usefulness of laser in the surgical treatment of these tumours particularly if
      small in size, is underlined.

PMID- 17041541
TI  - The condyle-fossa relationship in temporomandibular disorders. Considerations on
      the pathogenetic role of the disc.
AB  - AIM: The purpose of this study is to evaluate the condylar position and its
      variation in patients with temporomandibular joint (TMJ) disorders before and
      after therapy with occlusal gnathologic devices. METHODS: Twenty-five TMJ of 25
      patients with temporomandibular joint disorder were examined by linear
      measurement of the anterior, posterior and superior joint space between the
      condyle and glenoid fossa through cephalometric analysis on X-ray tomography of
      the TMJ and by calculating the condylar position with the Pullinger and Hollender
      method. RESULTS: The average condylar position in the TMJ with DTM was posterior
      with a mean value of 22.2% and a range from 14.3% to 36%. The condylar position
      of 25 TMJs was: anterior 0(0%); centric 8(32%) and posterior 17(68%). After
      therapy with occlusal gnathologic devices the average condylar position was
      centric with a mean value of 0.6% and a range from 5.3% to 6.6%. The condylar
      position of 25 TMJs was: anterior 2(8%); centric 22(88%) and posterior 1 (14%).
      CONCLUSIONS: The hypothesis can be advanced that joint pathology is the
      consequence of the alteration of the condyle position and therefore of the
      mandibular movement and vice versa. Therapy with occlusal devices makes it
      possible to modify the condylar position by increasing the condylar capability to
      recapture the joint disc.

PMID- 17041543
TI  - Clinical evaluation of an ointment with 10% metronidazole and 2% lidocaine in the
      treatment of alveolitis.
AB  - AIM: In this study, the authors evaluate the use of a 10% metronidazole and 2%
      lidocaine ointment, using a lanolin base and mint as flavoring, to treat
      alveolitis in humans. METHODS: Twenty-five patients, with a diagnosis of
      alveolitis, were treated in the following way: locoregional anesthesia; surgical
      cleaning of the socket with alveolar curettes; saline solution irrigation with a
      20 ml disposable syringe; and complete filling of the socket with the ointment.
      RESULTS: The analysis of the results showed that the painful symptoms were severe
      before and on the day of the treatment in 17 (68%) of the 25 patients treated.
      Post-treatment analysis presented 2 patients (18%) with severe painful symptoms
      after 24 h of the treatment and complete remission of painful symptoms after 48 h
      of the treatment with the ointment. CONCLUSIONS: Based on the results, it is
      possible to conclude that the 10% metronidazole and 2% lidocaine ointment, with
      mint flavoring and lanolin as a base, can be used to treat alveolitis.

PMID- 17041544
TI  - Effectiveness of a glutaraldehyde formulation in decontamination of dental unit
      water systems.
AB  - AIM: Dental-medical devices may transmit infections caused by bacteria that are
      usually found in water distribution systems, and which are difficult to treat and
      control. High bacterial contamination in the water systems of dental units is due
      to the presence of biofilm inside the pipes. Our study evaluated the efficacy of
      glutaraldehyde formulated with quarternary ammonium salts (Sanicide T4) examined
      in a previous study, employing a series of assays to confirm or otherwise the
      results obtained previously. METHODS: A purification protocol for the dental unit
      water system, together with a protocol for daily maintenance treatment, were
      tested on two dental units (in the Departments of Conservative and Prosthetic
      Dentistry) taking specimens from the turbine, micro-engine and air-water gun. The
      chemical substance, at a concentration of 20 cc per litre of water, was allowed
      to act when the department closed, for a total of 15 days. The Sanicide T4 was
      handled with protective gloves and the dental units were fitted with two safety
      devices to avoid accidental ingestion. RESULTS: Laboratory results enabled us to
      compare values for bacterial load at 36 degrees C and at 22 degrees C and for
      Pseudomonas aeruginosa, before and after applying the test protocol. Data
      obtained are satisfactory except for Pseudo-monas in the fountain in the
      Department of Conservative Dentistry; the value was in any case below the safety
      level set by the American Dental Association, confirming the results obtained in
      our previous study. CONCLUSIONS: The two protocols may now be considered an
      excellent solution to control the development of biofilm. Should the product be
      found to be effective for a longer period of use, each dental unit should be
      provided with: an anti-reflux valve to stop accidental ingestion of disinfectant;
      a hydraulic mechanism to pump the product to the handpieces and other water
      supply devices; possibility of discriminating the use of the public water system
      from the use of that in the disinfectant circuit; an automatic mechanism whereby
      the disinfectant can be flushed out with drinking water every morning.

PMID- 17041545
TI  - Caries-risk assessment: the role of salivary tests.
AB  - Although the incidence of caries has diminished dramatically over the past 3
      decades, small groups of subjects remain highly susceptible and do not respond to
      conventional preventive programs. An accurate individual caries-risk assessment
      allows to identify the etiological factors responsible for the disease and design
      a rational approach to treatment, addressed to the specific needs of the
      patients. The use of appropriate caries-risk prediction models, which include the
      use of simple chairside caries-susceptibility salivary tests, is the most
      suitable and modern approach to the problem. A review of the literature on
      salivary tests, at present available, able to identify the factors contributing
      to caries susceptibility, is presented. Each test is accurately described, with
      regard both to its procedure and the interpretation of its results:

PMID- 17041546
TI  - Facial nerve paralysis following mandibular trauma: a case report.
AB  - A strong posteriorly directed force applied to the mandible resulting in
      fracture, can also displace the mandibular condyle towards the external auditory
      canal or superiorly against the mandibular fossa, causing its penetration into
      the middle cranial fossa or even the fracture of the temporal bone. We report the
      case of a 30-year-old male patient victim of a bicycle accident that developed
      facial expression muscles paralysis on the left side soon after the trauma. On
      physical examination he presented left side postauricular ecchymosis, diminished
      muscular tonus of the left mouth angle and difficulty to close the left eye, he
      did not present clinical signs of facial fractures. The neurological and CT scan
      examination revealed fracture of the left temporal bone with total facial
      expression muscles paralysis. The patient was referred to the neurosurgical team
      for evaluation and they opted for a conservative treatment. After 3 months the
      patient showed a marked improvement with almost normal facial expression muscle
      movements. The trauma dynamics and treatment details are discussed.

PMID- 17041547
TI  - A review of endoparasitic acarines of Malaysia with special reference to novel
      endoparasitism of mites in amphibious sea snakes and supplementary notes on
      ecology of chiggers.
AB  - Some 2,000 species of mites of the family Trombiculidae are known in the world.
      The 6-legged larvae are mostly ectoparasites of reptiles, birds, mammals and
      invertebrates. Their 8-legged active nymphs and adults are free-living predators.
      In the Asia-Pacific region, a few species in various genera are vectors of scrub
      typhus and scrub-itch. In this a paper, a very bizarre trombiculid species,
      Vatacarus ipoides Southcott 1957, endoparasitic in the trachea of the amphibious
      sea snake, Laticauda colubrina (Schenider) is re-described based mostly on new
      born larvae reared in the laboratory. Life history study of the mite produced
      very novel and interesting results. A brief account of the life-cycle was
      presented at the first laboratory demonstration of the Malaysian Society of
      Parasitology and Tropical Medicine Meeting by Nadchatram and Audy (1965). The
      life history is illustrated and described here in greater detail. The active
      nymphal, and the akinetic teleiophane stages are bypassed, which is unusual in
      the life-cycle of the family Trombiculidae. Also, the larva is the only stage in
      the life-cycle that feeds. The sexes are predetermined in the larval neosomatic
      stage and give rise to small males and bigger females. Having obtained adults of
      the species, by rearing, it is deemed unnecessary for the original proposal by
      Southcott to erect a new family, Vatacaridae, because the adults share all the
      attributes of the family Trombiculidae. The male and female obtained through
      laboratory rearing are illustrated for the first time. Relationship of V. ipoides
      with Laticauda snakes show close host-specificity, in a group of acarines that
      are generally habitat-specific. Possible explanations for their association are
      discussed. The unusual morphology and the formation of new structures during an
      instar is of ontogenetic and evolutionary importance. The hypertrophic larvae are
      superficially vermiform, rather than typically acarine in shape. This, and other
      biological features, necessitated the proposal of new morphological terms, and
      they are discussed here.

PMID- 17041548
TI  - Daily feeding of fresh Neem leaves (Azadirachta indica) for worm control in
      sheep.
AB  - This study was Conducted To Evaluate The Anthelmintic Effect Of Neem (azadirachta
      Indica) On Nematode Parasites Of Sheep. Twelve Santa Ines Cross Bred Sheep From A
      Government Farm were randomly selected and equally divided into control (n = 6)
      and treated groups (n =6). Faecal egg counts (FEC) using the modified McMaster
      technique and the FAMACHA score for assessing clinical anaemia were carried out
      daily and recorded for 6 weeks. At the end of the study all the animals were
      slaughtered and the total worm count (TWC) was done. The results of FEC showed
      that there was no significant difference between the control and treated group (p
      = 0.081). However, worm burden estimations showed that the number of parasites
      was significantly higher in the control group compared to the treated group (p <
      0.05). This result indicated that feeding Neem had an effect on worm numbers in
      sheep, but was not reflected in their faecal egg counts. Further work is needed
      to reconfirm the effect of Neem on helminth infections of sheep.

PMID- 17041549
TI  - Use of molecular tools to distinguish Entamoeba histolytica and Entamoeba dispar
      infection among the aborigines in Cameron Highlands.
AB  - Amoebiasis is an infectious diseased caused by parasitic one-celled protozoan
      called Entamoeba histolytica. Numerous protozoa also can inhabit the gastro
      intestinal tract of human. Majority of these protozoa are non-pathogenic
      commensals or only causes disease under certain circumstances. Morphologically,
      E. histolytica, the invasive form, share the same characteristic with the
      nonpathogenic form, E. dispar. Both strains can be distinguished by using DNA
      identification. Many previous researches in Malaysia only reported infection with
      E. histolytica infection. Therefore in this study we tried to classify infection
      among the aborigines in Cameron Highland as true E. histolytica or E. dispar by
      Nested Polymerase Chain Reaction (Nested PCR) and Restriction enzyme (RE)
      digestion. Results showed that 31 samples were positive by microscopic
      examination, however of these 28 (13.2%) samples were positive for E. histolytica
      and 12 (5.6%) samples were positive for E. dispar by molecular tools.

PMID- 17041550
TI  - Field evaluation of Bacillus thuringiensis H-14 against Aedes mosquitoes.
AB  - Studies were carried out on the residual efficacy of Bacillus thuringiensis H-14
      (water dispersible granule, VectoBac ABG 6511) as direct application in the
      control of Aedes larvae in the field. Field Aedes sp populations in the earthen
      and glass jars were predetermined before initiation of the trial. On confirmation
      of the presence of Aedes species in the designated area, Sungai Nibong Kecil,
      Penang Island, Malaysia, Bti was introduced in the 55L earthen and 3L glass
      jars). Two test designs were carried out. The first design had treated water
      replenished daily with 6L of seasoned water and the second design is without the
      replenishment of water but evaporated water was replenished. Bti was effective in
      the field for at least 35 days with more than 80% reduction in the Aedes larvae
      in the treated containers. For earthen jars with daily replenishment of water,
      100% reduction was recorded for the first 3 days, while more than 80% reduction
      was recorded up to day 40. At day 60, Bti still provided an efficacy of 54.32 +/-
      4.61 (%) of reduction. Whilst for earthen jars without daily replenishment of
      water, 100% reduction was recorded for the first 5 days, while more than 80% of
      reduction was recorded up to day 40. For the glass jars studied, similar efficacy
      was observed. In jars with daily replenishment of water a better larval control
      was observed. Percentage of reduction from day 50 to 60 for replenishment of
      water was between 50 to 70% compared to without replenishment of water with less
      than 40%.

PMID- 17041551
TI  - Recovery of phosphatase and transaminase activity of mercury intoxicated Mus
      musculus (Linn.) liver tissue by Tribulus terrestris (Linn.) (Zygophyllaceae)
      extract.
AB  - The efficacy of the methanolic fraction (MF) of Tribulus terrestris fruit extract
      on mercury intoxicated mice, Mus musculus has been studied. At a median-lethal
      dose of mercuric chloride (12.9 mg/kg body wt.) administration an enhanced level
      of glutamate oxaloacete transaminase (GOT), glutamate pyruvate transminase (GPT)
      and simultaneously decreased level of acid phosphatase (ACP) and alkaline
      phosphatase (ALT) activities were noticed in the liver. Due to the mercury
      toxicity the liver cells are damaged to cause the alterations in their enzymes.
      During the recovery period, all the enzymological parameters are restored to
      reach near normal level. The result suggested that the oral administration of MF
      of T. terrestris fruit extract has (6 mg/kg body wt.) provided protection against
      the mercuric chloride induced hepatic damage in the mice, M. musculus.

PMID- 17041552
TI  - Quantitative analysis of the expression of p53 gene in colorectal carcinoma by
      using real-time PCR.
AB  - Colorectal carcinoma ranks third among ten leading causes of cancer in Malaysia.
      The colorectal carcinoma tumourigenesis involves the inactivation of tumour
      suppressor genes, and activation of proto-oncogenes. The p53 is one of the tumour
      suppressor genes that is involved in the colorectal carcinogenesis. The p53 gene
      is located on human chromosome 17p13.1 and comprises of 11 exons. Deficiencies in
      the p53 gene can cause the cancerous cells to spread to distant organs such as
      liver, lungs, lymph nodes, spine and bone. The most common p53 abnormalities that
      can lead to the metastasis of colorectal tumours are mutation and deregulation of
      the gene. In this study, nine colorectal carcinoma samples were used to establish
      a simple and sensitive strategy in the study on in vivo p53 expression by using
      realtime LightCycler SYBR Green I technology.

PMID- 17041553
TI  - Condemnation of lungs in abattoirs in peninsular Malaysia due to parasitic
      infection from 1998-2004.
AB  - A study on causes of lung condemnation in 25 abattoirs from peninsular Malaysia
      for a period of seven years (1998-2004) was conducted by examining the records at
      the Department of Veterinary Services headquarters in Kuala Lumpur. A total of
      5.3% of lungs from 233,417 cattle and buffaloes were condemned from 1998 to 2004.
      The main cause of condemnation was congestion (2.98%). The percentage of lungs
      that were condemned due to parasitic infection among the total population
      slaughtered was low (0.11%). Parasitic infection contributed to 2.1% of all lungs
      condemned. It was also found that the prevalence of parasitic infection in the
      lungs was generally much higher in buffaloes than in cattle.

PMID- 17041554
TI  - A transmission electron microscopy study on effects of a modified Glutaraldehyde
      fixation on Acanthamoeba castellanii.
AB  - Transmission electron microscopy (TEM) can provide high resolution imaging of
      biological specimens. The study is to establish the effects of a modified
      glutaraldehyde (GA) compare to the standard GA fixation on Acanthamoeba
      castellanii from TEM perspectives and thus provide precise and accurate
      information on the ultrastructure studies of the parasite. By increasing the
      contrast, the ultrastructures of the parasite were more evident. The TEM images
      were obtained from parasites fixed with the modified GA and the standard GA and
      then the area of the nucleus and the gray values of the image of the nucleus of
      the parasites were measured. The mean areas of the nucleus were found to be
      significantly reduced in the standard GA fixed parasites (12210.4 nm2) compared
      to the modified GA fixed parasites (8676.3 nm2) (p < 0.05). The mean gray values
      of the image were significantly reduced from 2024 in the standard GA fixed
      parasites (2024) to the modified GA fixed parasites (1636) (p < 0.05). The study
      shows that the modified GA produced significantly better contrast on TEM images
      of the A. castellanii compared to the standard GA. This was because the modified
      GA generated more free water molecules during fixation and the uptake of modified
      GA by the nucleus of the parasite organizing all protein constituents in the cell
      into a more closely packed configuration than that of the standard GA. With such
      properties, the modified GA is a better fixative providing better images for
      ultrastructures of the parasite.

PMID- 17041555
TI  - Prevalence and factors related to smoking among secondary school students in Kota
      Tinggi District, Johor, Malaysia.
AB  - Smoking among adolescent is a public health concern in Malaysia. Multiple studies
      on smoking prevalence and its related factors have been conducted in Malaysia,
      however, they were specific to either urban or rural areas alone. Studies in
      mixed settlement areas (urban, rural, land development area) had not been
      intensively investigated. This study reports the prevalence, demographic and
      factors related to smoking amongst form four students in the district of Kota
      Tinggi, Johor. A cross-sectional study of 16-year old secondary school students
      in Kota Tinggi district was conducted using two-stage stratified, proportionate
      sampling in July 2005. The study instrument used was a validated structured
      questionnaire on smoking and its related factors. Smoking prevalence was found to
      be 29.7%. More than 50% of male students were smokers. Prevalence was highest in
      FELDA (Federal Land Development Authority) settlement areas. Smoking was
      associated with having a brother or friend who smokes and poor academic
      performance. The study revealed that smoking prevalence was high, especially
      among male students in land development schemes. This situation will contribute
      to high smoking-related health problems in the future if proper preventive
      measures are not taken accordingly.

PMID- 17041556
TI  - Spatial, environmental and entomological risk factors analysis on a rural dengue
      outbreak in Lundu District in Sarawak, Malaysia.
AB  - The objective of this study was to elucidate the association of various risk
      factors with dengue cases reported in Lundu district, Sarawak, by analyzing the
      interaction between environmental, entomological, socio-demographic factors.
      Besides conventional entomological, serological and house surveys, this study
      also used GIS technology to generate geographic and environmental data on Aedes
      albopictus and dengue transmission. Seven villages were chosen based on the high
      number of dengue cases reported. A total of 551 households were surveyed. An
      overall description of the socio-demographic background and basic facilities was
      presented together with entomological and geographical profiles. For serological
      and ovitrap studies, systematic random sampling was used. Serological tests
      indicated that 23.7% of the 215 samples had a history of dengue, either recent or
      previous infections. Two samples (0.9%) were confirmed by IgM ELISA and 49
      samples (22.8%) had IgG responses. A total of 32,838 Aedes albopictus eggs were
      collected in 56 days of trapping. Cluster sampling was also done to determine
      whether any of the risk factors (entomological or geographical) were influenced
      by geographical location. These clusters were defined as border villages with
      East Kalimantan and roadside villages along Lundu/Biawas trunk road. The data
      collected were analyzed using SPSS version 10.01. Descriptive analysis using
      frequency, means, and median were used. To determine the association between
      variables and dengue cases reported, and to describe the differences between the
      two clusters of villages, two-sample t-test, and Pearson's Chi-Square were used.
      Accurate maps were produced with overlay and density function, which facilitates
      the map visualization and report generating phases. This study also highlights
      the use of differential Global Positioning System in mapping sites of 1m
      accuracy. Analysis of the data revealed there are significant differences in
      clusters of villages attributable to container density, house density, distance
      of the house from the main road, and number of Ae. albopictus eggs from ovitraps
      set indoor, outdoor and in dumping sites (Person's Chi-Square = 6.111, df = 1, p
      < 0.01). Further analysis using t-test showed that house density, container
      density, indoor mosquitoes egg count, outdoor mosquitoes egg count, and dumping
      sites mosquitoes egg count were higher at the roadside villages compared to
      border villages. A number of potential risk factors including those generated
      from GIS were investigated. None of the factors investigated in this study were
      associated with the dengue cases reported.

PMID- 17041557
TI  - Detection of insecticides resistance status in Culex quinquefasciatus and Aedes
      aegypti to four major groups of insecticides.
AB  - The resistance to various insecticides from 4 major groups (organochlorine,
      organophosphate, carbamate and pyrethroid) was investigated in a field strain of
      Culex quinquefasciatus from Baan Suan community, Nonthaburi province, Thailand by
      using a standard World Health Organization susceptibility test. The Baan Suan
      strain was completely resistant to DDT and highly resistant to deltamethrin,
      permethrin, fenitrothion and propoxur but this strain was still found to be
      highly susceptible to malathion. This strain displayed high resistance to
      cypermethrin since the result revealed that the resistance ratio of the 50%
      lethal concentration value (RR50) between the field and the laboratory strains
      (NIH strain) was 16. The study indicated that mosquitoes were resistant to almost
      all insecticide tested except malathion and this should be an alternative for Cx.
      quinquefasciatus control in this area. Moreover, Aedes aegypti, which is a main
      dengue vector in Baan Suan community was also tested with deltamethrin,
      permethrin and fenitrothion. The results showed that dengue mosquitoes are
      clearly resistant to permethrin and tolerant to deltamethrin, but was 100%
      susceptible to fenitrothion. The cause of insecticide resistance in Cx.
      quinquefasciatus may be due to the continuous use of insecticide for dengue
      vector control programme in Baan Suan community.

PMID- 17041558
TI  - Some epidemiological aspects of intestinal parasites in women workers before
      going abroad.
AB  - A study was conducted in Jakarta on 903 women workers before going abroad through
      stool examination by Ritchie's technical method. Of the women workers studied,
      640 subjects (70.87%) were found to be infected with intestinal parasites either
      helminthes, protozoa or combination. Out of those infected, 451 (70.47%) subjects
      were infected with intestinal helminthes, namely Ascaris lumbricoides (38.13%),
      Trichuris trichiura (28.13%), a combination of Necator americanus and Ancylostoma
      duodenale (13.59%) and Enterobius vermicularis (4.84%). In addition 319 (49.84%)
      subjects were infected with intestinal protozoa namely Giardia lamblia (22.03%),
      Entamoeba histolytica (14.53%), Blastocystis hominis (6.56%) and Entamoeba coli
      (6.72%). The youngest age to be affected was 14 years old (14.19% of the subjects
      studied). Majority (72.09%) of the study subjects received junior high school
      level of education. Home yard (46.51%) and ground under the trees (22.09%) were
      places favourable for the habits of defaecation, whereas garbage disposal took
      place in 52.33% home yards and 25.58% creeks. This study revealed that various
      life style habits and indiscriminate defaecation were the causes of the
      continuous transmission of intestinal parasitic infections. The different
      parasites that were found in women workers before going abroad relate to the
      various epidemiological aspects of intestinal parasites in women workers in
      Indonesia who came from different islands in the country and possessed different
      life style patterns, socioeconomic status, geographical condition and cultures.

PMID- 17041559
TI  - A cost-effective modified micromethod for measuring urine iodine.
AB  - A modified micromethod for measuring urine iodine was successfully established
      and validated. The micromethod showed good correlation with the method used by
      several World Health Organization (WHO) collaborative laboratories (y = 0.9342x +
      4.6213; r = 0.962; p = 0.01; n = 50). The micromethod also showed good agreement
      when compared to the reference WHO method. The sensitivity of the assay was
      13.809 ug/L (n = 8) and mean recoveries were 114, 103 and 106% at concentrations
      of 30, 40 and 50 ug/L (n = 3) respectively. At iodine concentrations of 51 +/-
      15.5, 108 +/- 32.4 and 149 +/- 38.6 ug/L, intra-assay coefficient of variations
      (CVs) were 13%, 7% and 5% respectively (n = 20), and inter-assay CVs were 10%,
      15% and 7% respectively (n = 10). The assay showed good linearity plot (y =
      1.0407x + 60.451; r = 0.993; n = 3).

PMID- 17041560
TI  - Infection of Blastocystis hominis in primary schoolchildren from Nakhon Pathom
      province, Thailand.
AB  - A study was conducted to evaluate the infection status of Blastocystis hominis in
      children from four public schools in Phuttamonthon district, Nakhon Pathom
      province, Thailand during November to December 2004. A total of 814 faecal
      specimens were used for B. hominis cultivation using Jones' medium. Mixed
      infections with other intestinal parasites were also examined by formalin ethyl
      acetate concentration method. It was found that 13.51% (110 of 814) of the
      children examined were infected with B. hominis. Mixed infections with other
      intestinal protozoa and helminths were observed in 10.91% (12 of 110) of B.
      hominis positive specimens. There were Giardia lamblia cysts (4.55%), Trichomonas
      hominis trophozoites (1.82%), Entamoeba histolytica cysts (0.91%), Endolimax nana
      cysts (0.91%), Strongyloides stercoralis larvae (0.91%), hookworm eggs (0.91%),
      and Trichuris trichiura eggs (0.91%). Of the children positive for B. hominis,
      there was no significant differences between sex (P > 0.05) and showed no
      correlation between age and the percentage of infection. The different infection
      rates among four schools indicated the involvement of hygienic factors which
      promoted the infection of this common intestinal protozoan. Variation in size of
      B. hominis was found in culture medium, which might indicate to the presence of
      different strains of B. hominis infection.

PMID- 17041561
TI  - The application of PCR-ELISA to the detection of Trypanosoma congolense type
      savannah (TCS) in bovine blood samples.
AB  - PCR-ELISA was set up to detect strains of Trypanosoma congolense type savannah
      (TCS) in field samples of buffy coats. Results of PCR-ELISA and PCR were compared
      and the effectiveness of both techniques was also compared with the Murray's
      method for the detection of TCS in 257 bovine buffy coats. The PCR products were
      labelled with digoxigenin (DIG-dUTP) during amplification cycles of the
      repetitive satellite DNA. A biotinylated DNA capture probe was used to detect the
      PCR products by ELISA in streptavidin coated microplates. Both the PCR-ELISA and
      PCR were more sensitive and more specific than the Murray's method. Of the 257
      buffy coats analysed by the three techniques, PCR-ELISA and PCR detected TCS in
      98 and 97 buffy coats respectively, whereas the Murray's method detected only 39
      samples. PCR-ELISA and PCR had almost the same sensitivity and specificity. PCR
      ELISA and PCR respectively detected TCS in 39.2% and 38.6% in all the 334 samples
      analysed by both techniques in this study.

PMID- 17041562
TI  - Notes on some ectoparasites received by the Medical Entomology Unit, Institute
      for Medical Research.
AB  - There were a spate of recent complaints of insect bites and the entomological
      specimens received from various sources were identified to be those of cat flea
      (Ctenocephalides felis) and rat flea (Xenopsylla cheopis), the tropical bed-bug
      (Cimex hemipterus) and the dog louse (Heterodoxus spiniger). Only the fleas and
      the bed-bug are known to attack humans.

PMID- 17041564
TI  - Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2
      as a chemosensitizer in cancer therapy.
AB  - Bcl-2 is an oncoprotein that plays a critical role in inhibiting apoptotic cell
      death in the mitochondria-dependent pathway in cancer chemotherapy. As a strategy
      for blocking Bcl-2 for enhancement of the chemotherapeutic effect, antisense Bcl
      2 (AS Bcl-2; G3139, oblimersen sodium, Genasense) has shown promise, and there
      are several ongoing clinical studies with hematological malignancies as well as
      solid tumors. Although several preclinical and clinical studies have shown the
      therapeutic efficacy of Bcl-2 in combination with an anticancer drug as a
      chemosensitizer, in clinical trials the downregulation of Bcl-2 has not been
      observed with a high frequency in tumor cells. Nevertheless, previous studies
      showed nonantisense effects such as production of reactive oxygen species and
      immunostimulatory action through cytosine-phosphate-guanosine-motif in the
      antisense oligodeoxynucleotides. Further, Bcl-2 is able to inhibit Beclin 1
      dependent autophagic cell death, which is a nonapoptotic cell death. The current
      status and future directions of AS Bcl-2 and the potential mechanisms for
      multiple roles that Bcl-2 has in cancer therapy are reviewed.

PMID- 17041563
TI  - International Society for Cell and Gene Therapy of Cancer: 2005 meeting in
      Shenzhen, China.
AB  - The 2005 International Society for Cell and Gene Therapy of Cancer (ISCGT)
      Congress was held in Shenzhen, China (www.iscgtchina2005.com) from December 9th
      11th 2005. Here, we describe a representation of the most seminal presentations
      providing an overview of the progress in the field of cancer gene therapy
      including the successful introduction of the first approved gene therapy drug.

PMID- 17041565
TI  - Intramucosal gastric adenocarcinoma of poorly differentiated type in the young is
      characterized by Helicobacter pylori infection and antral lymphoid hyperplasia.
AB  - The aim of this investigation was to clarify the histological characteristics of
      gastric cancer in the young. Twenty-three surgically resected specimens of young
      patients (under 30 years of age; young group) with intramucosal cancer of poorly
      differentiated type and 42 surgically resected specimens of elderly patients
      (more than 40 years of age; elderly group) with tumors of the identical depth and
      histological type were examined. The degree of gastritis and Helicobacter pylori
      (H. pylori) infection was evaluated according to the updated Sydney system. The
      incidence of H. pylori infection was significantly higher in the young group than
      in the elderly group (96 vs 36%, P<0.05). Within the background mucosa, antral
      chronic inflammatory infiltrates with lymphoid-follicle hyperplasia were more
      severe, and intestinal metaplasia was less frequent in the young group than in
      the elderly group. Glandular atrophy was not different between the two groups.
      Intramucosal gastric adenocarcinomas of poorly differentiated type in the young
      may be associated with H. pylori infection with antral chronic inflammation with
      lymphoid-follicle hyperplasia, regardless of the existence of intestinal
      metaplasia within the background gastric mucosa.

PMID- 17041566
TI  - Heparanase upregulation by colonic epithelium in inflammatory bowel disease.
AB  - Heparanase is an endo-beta-D-glucuronidase capable of cleaving heparan sulfate
      (HS) side chains at a limited number of sites, yielding HS fragments of still
      appreciable size ( approximately 5-7 kDa). Heparanase activity has long been
      detected in a number of cell types and tissues. Importantly, heparanase activity
      correlated with the metastatic potential of tumor-derived cells, attributed to
      enhanced cell dissemination as a consequence of HS cleavage and remodeling of the
      extracellular matrix barrier. Similarly, heparanase activity was implicated in
      neovascularization, inflammation and autoimmunity, involving migration of
      vascular endothelial cells and activated cells of the immune system. The
      involvement of heparanase in inflammatory processes of the gastrointestinal tract
      has not been examined. Here, we utilized immunohistochemical analysis to
      investigate heparanase expression in acute and chronic inflammatory conditions.
      Heparanase expression was not detected in specimens derived from normal colon
      tissue. In contrast, strong heparanase staining was observed in Crohn's disease
      and ulcerative colitis, but not in infectious colitis. Interestingly, heparanase
      staining was primarily observed in epithelial rather than immune cells.
      Importantly, un-fractionated as well as low molecular weight heparin
      (enoxaparin), which exhibit a strong inhibitory activity towards heparanase, have
      proven efficacious in ulcerative colitis and Crohn's disease patients, suggesting
      that heparanase is actively involved in these pathologies and thus may be
      considered as a target for the development of anti-inflammatory therapies.

PMID- 17041567
TI  - Chronic myelomonocytic leukemia: The role of bone marrow biopsy immunohistology.
AB  - The World Health Organization criteria for diagnosing chronic myelomonocytic
      leukemia (CMML) are largely based on findings observed in the peripheral blood
      and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy
      has not been adequately explored. We examined whether bone marrow biopsy
      supplemented by immunohistochemistry may be helpful in distinguishing CMML from
      cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia
      (aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which
      included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with
      those observed in six cases of chronic myelogenous leukemia and in three cases of
      atypical CML. In addition, we examined whether CD34 immunohistochemistry could be
      useful in separating cases of CMML with less than 10% blasts (type-1) from cases
      of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute
      transformation to acute myeloid leukemia (blasts > or = 20%). The presence of
      nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was
      used to highlight abnormal megakaryocytes. Our results demonstrate significant
      differences between the groups. CD34 analysis allowed separating CMML type-1 from
      type-2 and the former from CMML in acute transformation. CD123-positive
      plasmacytoid monocyte nodules were found only in CMML and not in the other two
      disease groups. Overlap between CMML and the other two groups were observed with
      CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and
      monocytes than CD68, but the differences between CMML and chronic myelogenous
      leukemia or atypical CML were still not significant. Although CD42b
      immunostaining facilitated the detection of dwarf megakaryocytes often present in
      CMML, the distinction between those and the small forms seen in chronic
      myelogenous leukemia was still problematic.

PMID- 17041568
TI  - Patient pathways for macular disease: what will the new optometrist with special
      interest achieve?

PMID- 17041570
TI  - Retinal detachment following meningococcal endophthalmitis.

PMID- 17041572
TI  - Locking the Luer lock.

PMID- 17041573
TI  - Ciliary body naevus.
AB  - PURPOSE: To describe clinical, ultrasound biomicroscopy (UBM), and
      histopathologic characteristics of benign melanocytic tumors of the ciliary body.
      DESIGN: Consecutive case series. METHODS: Six patients with a pigmented ciliary
      body tumour underwent complete ophthalmic examination and UBM, with
      histopathologic examination carried out on three cases. RESULTS: Six patients
      presented with a pigmented iridociliary mass, with central displacement of iris
      root. UBM revealed a stromal mass arising in pars plicata and/or pars plana in
      all six with a cyst in three cases (intrinsic=1 and extrinsic=2). Iridocyclectomy
      was performed because of documented growth in three cases, and all three cases
      proved to be ciliary body spindle-cell naevus. The other three patients have
      remained stable. CONCLUSIONS: On clinical basis and with available ancillary
      studies, ciliary body naevi cannot be reliably differentiated from ciliary body
      melanocytoma and ciliary body melanoma. Even with clinically documented growth,
      the lesions may prove to be ciliary body naevi.

PMID- 17041574
TI  - Epileptic convulsion following aspirin withdrawal before lid surgery.

PMID- 17041575
TI  - Pathological findings in the lens capsules and intraocular lens in chronic
      pseudophakic endophthalmitis: an electron microscopy study.
AB  - PURPOSE: The aim of this study was to describe the pathological findings in lens
      capsules and intraocular lens (IOL) studied by scanning and/or transmission
      electron microscopy (SEM and TEM, respectively) in a series of four eyes with
      chronic pseudophakic endophthalmitis (CPE). PATIENTS AND METHODS: We performed a
      retrospective study of four patients presenting CPE in whom surgical treatment
      with pars plana vitrectomy, capsulectomy with extraction of the IOL, and
      intravitreous antibiotic therapy was thereafter performed. The extracted IOL and
      the capsular remains were studied by SEM and/or TEM and microbiologic analysis of
      aqueous humour and vitreous aspirate was also carried out in all the cases.
      RESULTS: The presence of microorganisms was observed in the material analysed in
      all the cases studied. The use of TEM identified bacterial contamination by
      Staphylococcus spp and mixed contamination with microorganisms presenting a
      bacillar morphology suggestive of infection by Propionibacterium acnes in
      addition to the presence of cocci in the capsular remains. In another two cases,
      SEM localized colonies of Staphylococcus spp on the surface of the IOL in one
      case and mixed bacterial colonization with cocci plus filamentous bacteria in the
      other. The presence of macrophages associated with bacteria was observed in the
      capsular remains. CONCLUSIONS: Microorganisms were found in the IOL or the
      capsular material in the four cases studied, thereby explaining the
      refractoriness and severity of infection. The possible presence of polymicrobial
      infections, especially in the cases with filamentous bacteria, also explains the
      recurrence of infection.

PMID- 17041576
TI  - Phenotype of autosomal dominant cone-rod dystrophy due to the R838C mutation of
      the GUCY2D gene encoding retinal guanylate cyclase-1.
AB  - AIMS: To describe the phenotype of members of a large Caucasian British family
      affected by autosomal dominant cone-rod dystrophy due to an R838C mutation in the
      guanylate cyclase 2D (GUCY2D) gene encoding retinal guanylate cyclase-1 (RETGC
      1). METHODS: Retrospective review of 29 patients from four generations of the
      same family. RESULTS: Visual symptoms usually commenced in childhood. Only two
      patients, aged 14 and 25 years, had visual acuity compatible with driving. Of the
      12 patients aged over 40 years, eight (66%) had vision of counting fingers or
      worse and were eligible for blind registration in the UK. Of the 29 patients, 18
      (62%) had myopia greater than 5 D in at least one eye. Most had discernible
      macular changes on biomicroscopy, which varied from subtle RPE change to gross
      macular atrophy. All patients who underwent computerised perimetry exhibited a
      central or paracentral scotoma with normal peripheral field of vision. Of the 21
      patients who underwent electrodiagnostic testing, all exhibited decreased cone
      function, but rod function was normal in 12 (57%) patients. CONCLUSION: We
      believe this report highlights the importance of phenotype-genotype correlation
      in cone and cone-rod dystrophies. Increased understanding of the varying
      phenotypes associated with different genetic mutations allows appropriate
      counselling of patients. In addition, the phenotypic characterisation of the
      natural history of these conditions may prove valuable in the future should
      therapeutic interventions become available.

PMID- 17041577
TI  - Minimising blinding complications of cyclodiode laser in high risk and only eyes.

PMID- 17041578
TI  - Use of 18-gauge intravenous catheter needle for frontalis suspension in children
      with congenital ptosis.

PMID- 17041579
TI  - Screening for wet AMD by optometrists: resistance to change or professional
      rivalry?

PMID- 17041581
TI  - Making metallic glasses plastic by control of residual stress.
AB  - Metallic glasses, now that many compositions can be made in bulk, are of interest
      for structural applications exploiting their yield stress and yield strain, which
      are exceptionally high for metallic materials. Their applicability is limited by
      their near-zero tensile ductility resulting from work-softening and shear
      localization. Even though metallic glasses can show extensive local plasticity,
      macroscopically they can effectively be brittle, and much current research is
      directed at improving their general plasticity. In conventional engineering
      materials as diverse as silicate glasses and metallic alloys, we can improve
      mechanical properties by the controlled introduction of compressive surface
      stresses. Here we demonstrate that we can controllably induce such residual
      stresses in a bulk metallic glass, and that they improve the mechanical
      performance, in particular the plasticity, but that the mechanisms underlying the
      improvements are distinct from those operating in conventional materials.

PMID- 17041582
TI  - Phase inversion of particle-stabilized materials from foams to dry water.
AB  - Small particles attached to liquid surfaces arise in many products and processes,
      including crude-oil emulsions and food foams and in flotation, and there is a
      revival of interest in studying their behaviour. Colloidal particles of suitable
      wettability adsorb strongly to liquid-liquid and liquid-vapour interfaces, and
      can be sole stabilizers of emulsions and foams, respectively. New materials,
      including colloidosomes, anisotropic particles and porous solids, have been
      prepared by assembling particles at such interfaces. Phase inversion of particle
      stabilized emulsions from oil in water to water in oil can be achieved either by
      variation of the particle hydrophobicity (transitional) or by variation of the
      oil/water ratio (catastrophic). Here we describe the phase inversion of particle
      stabilized air-water systems, from air-in-water foams to water-in-air powders and
      vice versa. This inversion can be driven either by a progressive change in silica
      particle hydrophobicity at constant air/water ratio or by changing the air/water
      ratio at fixed particle wettability, and has not been observed in the
      corresponding systems stabilized by surfactants. The simplicity of the work is
      that this novel inversion is achieved in a single system. The resultant materials
      in which either air or water become encapsulated have potential applications in
      the food, pharmaceutical and cosmetics industries.

PMID- 17041583
TI  - High-performance transparent inorganic-organic hybrid thin-film n-type
      transistors.
AB  - High-performance thin-film transistors (TFTs) that can be fabricated at low
      temperature and are mechanically flexible, optically transparent and compatible
      with diverse substrate materials are of great current interest. To function at
      low biases to minimize power consumption, such devices must also contain a high
      mobility semiconductor and/or a high-capacitance gate dielectric. Here we report
      transparent inorganic-organic hybrid n-type TFTs fabricated at room temperature
      by combining In2O3 thin films grown by ion-assisted deposition, with nanoscale
      organic dielectrics self-assembled in a solution-phase process. Such TFTs combine
      the advantages of a high-mobility transparent inorganic semiconductor with an
      ultrathin high-capacitance/low-leakage organic gate dielectric. The resulting,
      completely transparent TFTs exhibit excellent operating characteristics near 1.0
      V with large field-effect mobilities of >120 cm2 V(-1) s(-1), drain-source
      current on/off modulation ratio (I(on)/I(off)) approximately 10(5), near-zero
      threshold voltages and sub-threshold gate voltage swings of 90 mV per decade. The
      results suggest new strategies for achieving 'invisible' optoelectronics.

PMID- 17041584
TI  - Effects of hydration on molecular junction transport.
AB  - The study of charge transport through increasingly complex small molecules will
      benefit from a detailed understanding of how contaminants from the environment
      affect molecular conduction. This should provide a clearer picture of the
      electronic characteristics of molecules by eliminating interference from adsorbed
      species. Here we use magnetically assembled microsphere junctions incorporating
      thiol monolayers to provide insight into changing electron transport
      characteristics resulting from exposure to air. Using this technique, current
      voltage analysis and inelastic electron tunnelling spectroscopy (IETS)
      demonstrate that the primary interaction affecting molecular conduction is rapid
      hydration at the gold-sulphur contacts. We use IETS to present evidence for
      changing mechanisms of charge transport as a result of this interaction. The
      detrimental effects on molecular conduction discussed here are important for
      understanding electron transport through gold-thiol molecular junctions once
      exposed to atmospheric conditions.

PMID- 17041585
TI  - Computational high-throughput screening of electrocatalytic materials for
      hydrogen evolution.
AB  - The pace of materials discovery for heterogeneous catalysts and electrocatalysts
      could, in principle, be accelerated by the development of efficient computational
      screening methods. This would require an integrated approach, where the catalytic
      activity and stability of new materials are evaluated and where predictions are
      benchmarked by careful synthesis and experimental tests. In this contribution, we
      present a density functional theory-based, high-throughput screening scheme that
      successfully uses these strategies to identify a new electrocatalyst for the
      hydrogen evolution reaction (HER). The activity of over 700 binary surface alloys
      is evaluated theoretically; the stability of each alloy in electrochemical
      environments is also estimated. BiPt is found to have a predicted activity
      comparable to, or even better than, pure Pt, the archetypical HER catalyst. This
      alloy is synthesized and tested experimentally and shows improved HER performance
      compared with pure Pt, in agreement with the computational screening results.

PMID- 17041586
TI  - Gbetagammas and the Ras binding domain of p110gamma are both important regulators
      of PI(3)Kgamma signalling in neutrophils.
AB  - Through their ability to regulate production of the key lipid messenger
      PtdIns(3,4,5)P(3), the class I phosphatidylinositol-3-OH kinases (PI(3)Ks)
      support many critical cell responses. They, in turn, can be regulated by cell
      surface receptors through signals acting on either their adaptor subunits (for
      example, through phosphotyrosine or Gbetagammas) or their catalytic subunits (for
      example, through GTP-Ras). The relative significance of these controlling inputs
      is undefined in vivo. Here, we have studied the roles of Gbetagammas, the adaptor
      p101, Ras and the Ras binding domain (RBD) in the control of the class I PI(3)K,
      PI(3)Kgamma, in mouse neutrophils. Loss of p101 leads to major reductions in the
      accumulation of PtdIns(3,4,5)P(3), activation of protein kinase B (PKB) and in
      migration towards G-protein activating ligands in vitro, and to an aseptically
      inflamed peritoneum in vivo. Loss of sensitivity of PI(3)Kgamma to Ras
      unexpectedly caused similar reductions, but additionally caused a substantial
      loss in production of reactive oxygen species (ROS). We conclude that
      Gbetagammas, p101 and the Ras-RBD interaction all have important roles in the
      regulation of PI(3)Kgamma in vivo and that they can simultaneously, but
      differentially, control distinct PI(3)Kgamma effectors.

PMID- 17041587
TI  - Input from Ras is required for maximal PI(3)K signalling in Drosophila.
AB  - Class I phosphoinositide 3-kinases (PI(3)Ks) are activated through associated
      adaptor molecules in response to G protein-coupled and tyrosine kinase receptor
      signalling. They contain Ras-binding domains (RBDs) and can also be activated
      through direct association with active GTP-bound Ras. The ability of Ras to
      activate PI(3)K has been established in vitro and by overexpression analysis, but
      its relevance for normal PI(3)K function in vivo is unknown. The Drosophila class
      I PI(3)K, Dp110, is activated by nutrient-responsive insulin signalling and
      modulates growth, oogenesis and metabolism. To investigate the importance of Ras
      mediated PI(3)K activation for normal PI(3)K function, we replaced Dp110 with
      Dp110(RBD), which is unable to bind to Ras but otherwise biochemically normal. We
      found that Ras-mediated Dp110 regulation is dispensable for viability. However,
      egg production, which requires large amounts of growth, is dramatically lowered
      in Dp110(RBD) flies. Furthermore, insulin cannot maximally activate PI(3)K
      signalling in Dp110(RBD) imaginal discs and Dp110(RBD) flies are small. Thus,
      Dp110 integrates inputs from its phosphotyrosine-binding adaptor and Ras to
      achieve maximal PI(3)K signalling in specific biological situations.

PMID- 17041588
TI  - CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and
      regulates histone methylation.
AB  - The CUL4-DDB1-ROC1 ubiquitin E3 ligase regulates cell-cycle progression,
      replication and DNA damage response. However, the substrate-specific adaptors of
      this ligase remain uncharacterized. Here, we show that CUL4-DDB1 complexes
      interact with multiple WD40-repeat proteins (WDRs) including TLE1-3, WDR5, L2DTL
      (also known as CDT2) and the Polycomb-group protein EED (also known as ESC). WDR5
      and EED are core components of histone methylation complexes that are essential
      for histone H3 methylation and epigenetic control at K4 or K9 and K27,
      respectively, whereas L2DTL regulates CDT1 proteolysis after DNA damage through
      CUL4-DDB1 (ref. 8). We found that CUL4A-DDB1 interacts with H3 methylated
      mononucleosomes and peptides. Inactivation of either CUL4 or DDB1 impairs these
      histone modifications. However, loss of WDR5 specifically affects histone H3
      methylation at K4 but not CDT1 degradation, whereas inactivation of L2DTL
      prevents CDT1 degradation but not histone methylation. Our studies suggest that
      CUL4-DDB1 ligases use WDR proteins as molecular adaptors for substrate
      recognition, and modulate multiple biological processes through ubiquitin
      dependent proteolysis.

PMID- 17041589
TI  - TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF.
AB  - Ypt-Rab GTPases are key regulators of the various steps of intracellular
      trafficking. Guanine nucleotide-exchange factors (GEFs) regulate the conversion
      of Ypt-Rabs to the GTP-bound state, in which they interact with effectors that
      mediate all the known aspects of vesicular transport. An interesting possibility
      is that Ypt-Rabs coordinate separate steps of the transport pathways. The
      conserved modular complex TRAPP is a GEF for the Golgi gatekeepers Ypt1 and
      Ypt31/32 (Refs 5-7). However, it is not known how Golgi entry and exit are
      coordinated. TRAPP comes in two configurations: the seven-subunit TRAPPI is
      required for endoplasmic reticulum-to-Golgi transport, whereas the ten-subunit
      TRAPPII functions in late Golgi. The two essential TRAPPII-specific subunits
      Trs120 and Trs130 have been identified as Ypt31/32 genetic interactors. Here, we
      show that they are required for switching the GEF specificity of TRAPP from Ypt1
      to Ypt31. Moreover, a trs130ts mutation confers opposite effects on the
      intracellular localization of these GTPases. We suggest that the Trs120-Trs130
      subcomplex joins TRAPP in the late Golgi to switch its GEF activity from Ypt1 to
      Ypt31/32. Such a 'switchable' GEF could ensure sequential activation of these
      Ypts, thereby coordinating Golgi entry and exit.

PMID- 17041590
TI  - Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore
      opening.
AB  - The molecular forces that drive structural transitions between the open and
      closed states of channels and transporters are not well understood. The gate of
      the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can
      open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight
      into the channel-opening mechanism, we measured interaction energies between the
      relevant side chains by double-mutant cycle analysis and correlated these with
      the channel activities of corresponding point mutants. The closed central salt
      bridge has a strong interaction energy of -5.6 kcal mol(-1), which can be broken
      by forming the open-state salt bridge Glu52-Lys82 (DeltaDeltaG(Inter) = -3.5 kcal
      mol(-1)) and a weak interaction between Arg138 and Glu128 (DeltaDeltaG(Inter) = 
      0.6 kcal mol(-1)). A covalent disulfide bond in place of the central salt bridge
      completely blocks the channel. Growth assays indicate that this gating mechanism
      could physiologically contribute to the osmoprotection of Escherichia coli cells
      from environmental stress.

PMID- 17041591
TI  - Memory modulates color appearance.
AB  - We asked human observers to adjust the color of natural fruit objects until they
      appeared achromatic. The objects were generally perceived to be gray when their
      color was shifted away from the observers' gray point in a direction opposite to
      the typical color of the fruit. These results show that color sensations are not
      determined by the incoming sensory data alone, but are significantly modulated by
      high-level visual memory.

PMID- 17041592
TI  - Activation of a presynaptic glutamate transporter regulates synaptic transmission
      through electrical signaling.
AB  - Whereas glutamate transporters in glial cells and postsynaptic neurons contribute
      significantly to re-uptake of synaptically released transmitter, the functional
      role of presynaptic glutamate transporters is poorly understood. Here, we used
      electrophysiological recording to examine the functional properties of a
      presynaptic glutamate transporter in rat retinal rod bipolar cells and its role
      in regulating glutamatergic synaptic transmission between rod bipolar cells and
      amacrine cells. Release of glutamate activated the presynaptic transporter with a
      time course that suggested a perisynaptic localization. The transporter was also
      activated by spillover of glutamate from neighboring rod bipolar cells. By
      recording from pairs of rod bipolar cells and AII amacrine cells, we demonstrate
      that activation of the transporter-associated anion current hyperpolarizes the
      presynaptic terminal and thereby inhibits synaptic transmission by suppressing
      transmitter release. Given the evidence for presynaptic glutamate transporters,
      similar mechanisms could be of general importance for transmission in the nervous
      system.

PMID- 17041593
TI  - 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic
      regulation of chromatin structure.
AB  - Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes
      responds to dietary manipulation such as the 'ketogenic diet'. Here we have
      investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in
      the rat kindling model of temporal lobe epilepsy. We show that 2DG potently
      reduces the progression of kindling and blocks seizure-induced increases in the
      expression of brain-derived neurotrophic factor and its receptor, TrkB. This
      reduced expression is mediated by the transcription factor NRSF, which recruits
      the NADH-binding co-repressor CtBP to generate a repressive chromatin environment
      around the BDNF promoter. Our results show that 2DG has anticonvulsant and
      antiepileptic properties, suggesting that anti-glycolytic compounds may represent
      a new class of drugs for treating epilepsy. The metabolic regulation of neuronal
      genes by CtBP will open avenues of therapy for neurological disorders and cancer.

PMID- 17041594
TI  - Phase-locking of hippocampal interneurons' membrane potential to neocortical up
      down states.
AB  - During quiet wakefulness and sleep, and under anesthesia, the membrane potentials
      of neocortical pyramidal neurons show synchronous, slow oscillations, so-called
      up-down states (UDS), that can be detected in the local field potential (LFP).
      The influence of this synchronized, spontaneous neocortical activity on the
      hippocampus is largely unknown. We performed the first in vivo whole-cell
      recordings from hippocampal dorsal CA1 interneurons and found that their membrane
      potentials were phase-locked to neocortical up-down states with a small delay.
      These results provide strong evidence for cortico-hippocampal interaction and
      suggest that neocortical activity drives hippocampal interneurons during UDS.

PMID- 17041595
TI  - How MT cells analyze the motion of visual patterns.
AB  - Neurons in area MT (V5) are selective for the direction of visual motion. In
      addition, many are selective for the motion of complex patterns independent of
      the orientation of their components, a behavior not seen in earlier visual areas.
      We show that the responses of MT cells can be captured by a linear-nonlinear
      model that operates not on the visual stimulus, but on the afferent responses of
      a population of nonlinear V1 cells. We fit this cascade model to responses of
      individual MT neurons and show that it robustly predicts the separately measured
      responses to gratings and plaids. The model captures the full range of pattern
      motion selectivity found in MT. Cells that signal pattern motion are
      distinguished by having convergent excitatory input from V1 cells with a wide
      range of preferred directions, strong motion opponent suppression and a tuned
      normalization that may reflect suppressive input from the surround of V1 cells.

PMID- 17041596
TI  - Interleukin-10 determines viral clearance or persistence in vivo.
AB  - Persistent viral infections are a major health concern. One obstacle inhibiting
      the clearance of persistent infections is functional inactivation of antiviral T
      cells. Although such immunosuppression occurs rapidly after infection, the
      mechanisms that induce the loss of T-cell activity and promote viral persistence
      are unknown. Herein we document that persistent viral infection in mice results
      in a significant upregulation of interleukin (IL)-10 by antigen-presenting cells,
      leading to impaired T-cell responses. Genetic removal of Il10 resulted in the
      maintenance of robust effector T-cell responses, the rapid elimination of virus
      and the development of antiviral memory T-cell responses. Therapeutic
      administration of an antibody that blocks the IL-10 receptor restored T-cell
      function and eliminated viral infection. Thus, we identify a single molecule that
      directly induces immunosuppression leading to viral persistence and demonstrate
      that a therapy to neutralize IL-10 results in T-cell recovery and the prevention
      of viral persistence.

PMID- 17041597
TI  - Oriented loading of FtsK on KOPS.
AB  - In Escherichia coli, the ATP-dependent DNA translocase FtsK transports DNA across
      the site of cell division and activates recombination by the XerCD recombinases
      at a specific site on the chromosome, dif, to ensure the last stages of
      chromosome segregation. DNA transport by FtsK is oriented by 8-base-pair
      asymmetric sequences ('KOPS'). Here we provide evidence that KOPS promote FtsK
      loading on DNA and that translocation is oriented at this step.

PMID- 17041598
TI  - Identification of the FtsK sequence-recognition domain.
AB  - FtsK is a prokaryotic multidomain DNA translocase that coordinates chromosome
      segregation and cell division. FtsK is membrane anchored at the division septum
      and, guided by highly skewed DNA sequences, translocates the chromosome to bring
      the terminus of replication to the septum. Here, we use in vitro single-molecule
      and ensemble methods to unveil a mechanism of action in which the translocation
      and sequence-recognition activities are performed by different domains in FtsK.

PMID- 17041599
TI  - Structural and biochemical basis for misfolded RNA recognition by the Ro
      autoantigen.
AB  - The Ro autoantigen is ring-shaped, binds misfolded noncoding RNAs and is proposed
      to function in quality control. Here we determine how Ro interacts with misfolded
      RNAs. Binding of Ro to misfolded precursor (pre)-5S ribosomal RNA requires a
      single-stranded 3' end and helical elements. As mutating most sequences of the
      helices and tail results in modest decreases in binding, Ro may be able to
      associate with a range of RNAs. Ro binds several other RNAs that contain single
      stranded tails. A crystal structure of Ro bound to a misfolded pre-5S rRNA
      fragment reveals that the tail inserts into the cavity, while a helix binds on
      the surface. Most contacts of Ro with the helix are to the backbone. Mutagenesis
      reveals that Ro has an extensive RNA-binding surface. We propose that Ro uses
      this surface to scavenge RNAs that fail to bind their specific RNA-binding
      proteins.

PMID- 17041600
TI  - R-spondin1 is essential in sex determination, skin differentiation and
      malignancy.
AB  - R-spondins are a recently characterized small family of growth factors. Here we
      show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome
      characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition
      to squamous cell carcinoma of the skin. Our data show, for the first time, that
      disruption of a single gene can lead to complete female-to-male sex reversal in
      the absence of the testis-determining gene, SRY.

PMID- 17041601
TI  - Abnormal skin, limb and craniofacial morphogenesis in mice deficient for
      interferon regulatory factor 6 (Irf6).
AB  - Transcription factor paralogs may share a common role in staged or overlapping
      expression in specific tissues, as in the Hox family. In other cases, family
      members have distinct roles in a range of embryologic, differentiation or
      response pathways (as in the Tbx and Pax families). For the interferon regulatory
      factor (IRF) family of transcription factors, mice deficient in Irf1, Irf2, Irf3,
      Irf4, Irf5, Irf7, Irf8 or Irf9 have defects in the immune response but show no
      embryologic abnormalities. Mice deficient for Irf6 have not been reported, but in
      humans, mutations in IRF6 cause two mendelian orofacial clefting syndromes, and
      genetic variation in IRF6 confers risk for isolated cleft lip and palate. Here we
      report that mice deficient for Irf6 have abnormal skin, limb and craniofacial
      development. Histological and gene expression analyses indicate that the primary
      defect is in keratinocyte differentiation and proliferation. This study describes
      a new role for an IRF family member in epidermal development.

PMID- 17041602
TI  - Essential role of Jun family transcription factors in PU.1 knockdown-induced
      leukemic stem cells.
AB  - Knockdown of the transcription factor PU.1 (encoded by Sfpi1) leads to acute
      myeloid leukemia (AML) in mice. We examined the transcriptome of preleukemic
      hematopoietic stem cells (HSCs) in which PU.1 was knocked down (referred to as
      'PU.1-knockdown HSCs') to identify transcriptional changes preceding malignant
      transformation. Transcription factors c-Jun and JunB were among the top
      downregulated targets. Restoration of c-Jun expression in preleukemic cells
      rescued the PU.1 knockdown-initiated myelomonocytic differentiation block.
      Lentiviral restoration of JunB at the leukemic stage led to loss of leukemic self
      renewal capacity and prevented leukemia in NOD-SCID mice into which leukemic PU.1
      knockdown cells were transplanted. Examination of human individuals with AML
      confirmed the correlation between PU.1 and JunB downregulation. These results
      delineate a transcriptional pattern that precedes leukemic transformation in PU.1
      knockdown HSCs and demonstrate that decreased levels of c-Jun and JunB contribute
      to the development of PU.1 knockdown-induced AML by blocking differentiation and
      increasing self-renewal. Therefore, examination of disturbed gene expression in
      HSCs can identify genes whose dysregulation is essential for leukemic stem cell
      function and that are targets for therapeutic interventions.

PMID- 17041603
TI  - Irf6 is a key determinant of the keratinocyte proliferation-differentiation
      switch.
AB  - The epidermis is a highly organized structure, the integrity of which is central
      to the protection of an organism. Development and subsequent maintenance of this
      tissue depends critically on the intricate balance between proliferation and
      differentiation of a resident stem cell population; however, the signals
      controlling the proliferation-differentiation switch in vivo remain elusive.
      Here, we show that mice carrying a homozygous missense mutation in interferon
      regulatory factor 6 (Irf6), the homolog of the gene mutated in the human
      congenital disorders Van der Woude syndrome and popliteal pterygium syndrome,
      have a hyperproliferative epidermis that fails to undergo terminal
      differentiation, resulting in soft tissue fusions. We further demonstrate that
      mice that are compound heterozygotes for mutations in Irf6 and the gene encoding
      the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show
      similar defects of keratinizing epithelia. Our results indicate that Irf6 is a
      key determinant of the keratinocyte proliferation-differentiation switch and that
      Irf6 and Sfn interact genetically in this process.

PMID- 17041604
TI  - The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt
      signaling, is mutated in inherited anonychia.
AB  - Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive
      conditions in which the only presenting phenotype is the absence or severe
      hypoplasia of all fingernails and toenails. After determining linkage to
      chromosome 20p13, we identified homozygous or compound heterozygous mutations in
      the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt
      signaling, in eight affected families. Rspo4 expression was specifically
      localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a
      crucial role in nail morphogenesis.

PMID- 17041605
TI  - Interface-disrupting amino acids establish specificity between T cell receptors
      and complexes of major histocompatibility complex and peptide.
AB  - T cell receptors (TCRs) bind complexes of cognate major histocompatibility
      complex (MHC) and peptide at relatively low affinities (1-200 microM).
      Nevertheless, TCR-MHC-peptide interactions are usually specific for the peptide
      and the allele encoding the MHC. Here we show that to escape thymocyte negative
      selection, TCRs must interact with many of the side chains of MHC-peptide
      complexes as 'hot spots' for TCR binding. Moreover, even when the 'parental' side
      chain did not contribute binding affinity, some MHC-peptide residues contributed
      to TCR specificity, as amino acid substitutions substantially reduced binding
      affinity. The presence of such 'interface-disruptive' side chains helps to
      explain how TCRs generate specificity at low-affinity interfaces and why TCRs
      often 'accommodate' a subset of amino acids at a given MHC-peptide position.

PMID- 17041606
TI  - Low mortality of children undergoing hematopoietic stem cell transplantation from
      7 to 8/10 human leukocyte antigen allele-matched unrelated donors with the use of
      antithymocyte globulin.
AB  - Human leukocyte antigen (HLA)-matched sibling donor hematopoietic stem cell
      transplantation (HSCT) is available for only approximately 30% patients needing
      HSCT. Use of alternative donors is associated with a high incidence and severity
      of graft-versus-host disease (GVHD). Here we report our experience with GVHD
      prophylaxis using pre-transplant rabbit antithymocyte globulin (rATG), in
      addition to post transplant cyclosporin A and methotrexate. Seventy-five children
      received unmanipulated grafts from 7 to 10/10 HLA allele-matched unrelated
      donors. Median follow-up was 25 months (range, 6-65 months). Only 2/75 patients
      (2.5%) developed acute GVHD grades III-IV, and 17/75 (25%) developed extensive
      chronic GVHD. Overall survival was 79%. It was similar in patients receiving
      grafts from 7 or 8/10 to 9 or 10/10 allele-matched donors, and similar in
      patients receiving peripheral blood stem cells and marrow. Six (11%) patients
      died owing to relapse, and 10 (13%) due to transplant-related complications. The
      addition of rATG appears to result in a low incidence of severe GVHD and overall
      mortality.

PMID- 17041607
TI  - Addressing parenting concerns of bone marrow transplant patients: opening (and
      closing) Pandora's box.
AB  - Although a significant number of adults undergoing stem cell transplant (SCT) or
      bone marrow transplantation (BMT) care for dependent children, and these
      treatments pose significant challenges for families, research has virtually
      ignored the impact of parenting on patients' quality of life during BMT/SCT and
      children's responses to having a parent undergo these treatments. Physicians
      rarely inquire about parenting concerns related to the extended hospitalizations
      necessitated by these treatments, yet clinical experience suggests that
      addressing patient concerns about children's reactions to cancer and BMT/SCT can
      improve the experience of the patient and the patient's family, and help the
      medical team respond effectively to sources of patients' distress. Parents
      frequently want to know what reactions to expect from children, thus general
      developmental information is reviewed, and recommendations given for when
      professional help for children is warranted. A key way for parents to support
      their children is with open, honest communication; however, parents often find it
      extremely difficult to talk about cancer and BMT/SCT with their children. The
      medical team can assist patients' efforts to communicate with and support their
      children by asking about a patient's children, providing some targeted
      information, and discussing the potential impact of treatments on parenting
      capacity. Inquiring about and addressing parenting concerns may initially seem
      difficult, but can ultimately facilitate stronger doctor-patient alliances, and
      more compassionate care.

PMID- 17041608
TI  - Bone marrow transplantation for cartilage-hair-hypoplasia.
AB  - The association of cartilage hair hypoplasia (CHH) with severe combined
      immunodeficiency (SCID) has been known for more than three decades. Bone marrow
      transplantation (BMT) remains the only effective treatment that might cure SCID.
      Surprisingly little has been reported on the experience with BMT in CHH. We
      report here survival and long-term reconstitution of immunity after BMT in three
      patients with CHH. Regardless of whether a related human leukocyte antigen
      matched or unrelated matched donors were used as the source of BMT, all patients
      are alive and well 5-20 years after BMT. Engraftment appears robust with most
      cells of donors origin. Repeated evaluation of the immune system showed normal
      cellular and humoral immunity. Our results should encourage the use of BMT in
      patients with CHH who have profound immunodeficiency.

PMID- 17041609
TI  - Autologous stem cell transplantation beyond 60 years of age.
AB  - Along with improved supportive care and thus reduced treatment-related mortality,
      an increasing number of elderly patients (> 60 years) with haematological
      malignancies are now considered for high-dose therapy (HDT) supported by
      autologous stem cell transplantation (ASCT). ASCT is feasible in selected elderly
      patients with multiple myeloma and those with non-Hodgkin's lymphoma. As elderly
      patients have generally been excluded from randomized studies evaluating efficacy
      of ASCT in comparison with non-transplant approaches, limited data are available
      on the efficacy of ASCT in this patient population. Recent developments in
      supportive care including amifostine and palifermin may increase feasibility of
      ASCT in elderly patients. Prospective studies are needed to evaluate feasibility
      and efficacy of ASCT in patients over 60 years of age. Also, further studies are
      needed in order to decrease toxicity of high-dose regimens in this patient group
      where co-morbid conditions may modify the toxicity of HDT in a clinically
      significant manner.

PMID- 17041610
TI  - Iron homeostasis in plants: when transcription affects translocation.

PMID- 17041612
TI  - The increasing importance of systematic reviews in clinical dermatology research
      and publication.

PMID- 17041616
TI  - CD95-mediated signals in the skin: going out with an (inflammatory) bang?
AB  - The death ligand CD95L (Fas/Apo-1-ligand) has been viewed as a proapoptotic
      molecule involved in the pathogenesis of T cell-mediated skin diseases including
      eczema. In the presence of inhibitors of caspases, CD95L induces proinflammatory
      genes in keratinocytes. This more pleiotropic function of CD95L as enhancer of
      inflammation may be equally important to apoptosis induction of keratinocytes, at
      least in eczema.

PMID- 17041617
TI  - The new keratin nomenclature.
AB  - When the first nomenclature of the keratin protein family was published over 20
      years ago, only 19 keratins were thought to exist. Sequencing of the human genome
      has now revealed that there are 54 keratin genes. As a consequence, the
      nomenclature needed revision to apply a logical numbering system that includes
      the more recently identified keratins of the hair follicle.

PMID- 17041618
TI  - A new nail in the CTCL coffin.
AB  - The impact of immunotherapy on the natural progression of cutaneous T-cell
      lymphoma (CTCL), particularly the mycosis fungoides and Sezary syndrome variants,
      has been based on our evolving understanding of the disease's immunobiology.

PMID- 17041621
TI  - Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that
      controls many aspects of cellular physiology, including transcription,
      translation, cell size, cytoskeletal organization and autophagy. Recent advances
      in the mTOR signaling field have found that mTOR exists in two heteromeric
      complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the
      integration of many signals, including growth factors, insulin, nutrients, energy
      availability and cellular stressors such as hypoxia, osmotic stress, reactive
      oxygen species and viral infection. In this review we highlight recent advances
      in the mTOR signaling field that relate to how the two mTOR complexes are
      regulated, and we discuss stress conditions linked to the mTOR signaling network
      that have not been extensively covered in other reviews. Given the diversity of
      signals that have been shown to impinge on mTOR, we also speculate on other
      signal-transduction pathways that may be linked to mTOR in the future.

PMID- 17041622
TI  - Insulin and amino-acid regulation of mTOR signaling and kinase activity through
      the Rheb GTPase.
AB  - Target of Rapamycin (TOR), a giant protein kinase expressed by all eucaryotic
      cells, controls cell size in response to nutrient signals. In metazoans, cell and
      organismal growth is controlled by nutrients and the insulin/insulin-like growth
      factor (IGF) system, and the understanding of how these inputs coordinately
      regulate TOR signaling has advanced greatly in the past 5 years. In single-cell
      eucaryotes and Caenorhabditis elegans, TOR is a dominant regulator of overall
      mRNA translation, whereas in higher metazoans, TOR controls the expression of a
      smaller fraction of mRNAs that is especially important to cell growth. TOR
      signals through two physically distinct multiprotein complexes, and the control
      of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the
      polypeptides raptor and LST8. Raptor is the substrate binding element of TORC1,
      and the ability of raptor to properly present substrates, such as the
      translational regulators 4E-BP and p70 S6 kinase, to the TOR catalytic domain is
      essential for their TOR-catalysed phosphorylation, and is inhibited by the
      Rapamycin/FKBP-12 complex. The dominant proximal regulator of TORC1 signaling and
      kinase activity is the ras-like small GTPase Rheb. Rheb binds directly to the
      mTOR catalytic domain, and Rheb-GTP enables TORC1 to attain an active
      configuration. Insulin/IGF enhances Rheb GTP charging through the ability of
      activated Akt to inhibit the Rheb-GTPase-activating function of the tuberous
      sclerosis heterodimer (TSC1/TSC2). Conversely, energy depletion reduces Rheb-GTP
      charging through the ability of the adenosine monophosphate-activated protein
      kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function,
      as well as by HIFalpha-mediated transcriptional responses that act upstream of
      the TSC1/2 complex. Amino-acid depletion inhibits TORC1 acting predominantly
      downstream of the TSC complex, by interfering with the ability of Rheb to bind to
      mTOR. The components of the insulin/IGF pathway to TORC1 are now well
      established, whereas the elements mediating the more ancient and functionally
      dominant input of amino acids remain largely unknown.

PMID- 17041623
TI  - Stress and mTORture signaling.
AB  - The TOR (target of rapamycin) pathway is an evolutionarily conserved signaling
      module regulating cell growth (accumulation of mass) in response to a variety of
      environmental cues such as nutrient availability, hypoxia, DNA damage and osmotic
      stress. Its pivotal role in cellular and organismal homeostasis is reflected in
      the fact that unrestrained signaling activity in mammals is associated with the
      occurrence of disease states including inflammation, cancer and diabetes. The
      existence of TOR homologs in unicellular organisms whose growth is affected by
      environmental factors, such as temperature, nutrients and osmolarity, suggests an
      ancient role for the TOR signaling network in the surveillance of stress
      conditions. Here, we will summarize recent advances in the TOR signaling field
      with special emphasis on how stress conditions impinge on insulin/insulin-like
      growth factor signaling/TOR signaling.

PMID- 17041624
TI  - Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three
      classes of nuclear RNA polymerases.
AB  - The target of rapamycin (TOR) signal-transduction pathway is an important
      mechanism by which eucaryotic cells adjust their protein biosynthetic capacity to
      nutrient availability. Both in yeast and in mammals, the TOR pathway regulates
      the synthesis of ribosomal components, including transcription and processing of
      pre-rRNA, expression of ribosomal proteins and the synthesis of 5S rRNA.
      Expression of the genes encoding the numerous constituents of ribosomes requires
      transcription by all three classes of nuclear RNA polymerases. In this review, we
      summarize recent advances in understanding the interplay among nutrient
      availability, transcriptional control and ribosome biogenesis. We focus on
      transcription in response to nutrients, detailing the relevant downstream targets
      of TOR in yeast and mammals. The critical role of TOR in linking environmental
      queues to ribosome biogenesis provides an efficient means by which cells alter
      their overall protein biosynthetic capacity.

PMID- 17041625
TI  - Cell growth control: little eukaryotes make big contributions.
AB  - The story of rapamycin is a pharmaceutical fairytale. Discovered as an antifungal
      activity in a soil sample collected on Easter Island, this macrocyclic lactone
      and its derivatives are now billion dollar drugs, used in, and being evaluated
      for, a number of clinical applications. Taking advantage of its antifungal
      property, the molecular Target Of Rapamycin, TOR, was first described in the
      budding yeast Saccharomyces cerevisiae. TORs encode large, Ser/Thr protein
      kinases that reside in two distinct, structurally and functionally conserved,
      multi-protein complexes. In yeast, these complexes coordinate many different
      aspects of cell growth. TOR complex 1, TORC1, promotes protein synthesis and
      other anabolic processes, while inhibiting macroautophagy and other catabolic and
      stress-response processes. TORC2 primarily regulates cell polarity, although
      additional readouts of this complex are beginning to be characterized. TORC1
      appears to be activated by nutrient cues and inhibited by stresses and rapamycin;
      however, detailed mechanisms are not known. In contrast, TORC2 is insensitive to
      rapamycin and physiological regulators of this complex have yet to be defined.
      Given the unsurpassed resources available to yeast researchers, this simple
      eukaryote continues to contribute to our understanding of eukaryotic cell growth
      in general and TOR function in particular.

PMID- 17041626
TI  - mTOR, translation initiation and cancer.
AB  - Control of mRNA translation plays a fundamental role in many aspects of cell
      metabolism. It constitutes a critical step in the control of gene expression, and
      consequently cell growth, proliferation and differentiation. Translation is
      regulated in response to nutrient availability, hormones, mitogenic and growth
      factor stimulation and is coupled with cell cycle progression and cell growth.
      Signaling by the PI3K/Akt/mTOR pathway profoundly affects mRNA translation
      through phosphorylation of downstream targets such as 4E-BP and S6K. Inhibitors
      of this pathway and thus cap-dependent translation are emerging as promising
      therapeutic options for the treatment of cancer.

PMID- 17041627
TI  - When translation meets transformation: the mTOR story.
AB  - There is currently a high level of interest in signalling through the mammalian
      target of rapamycin (mTOR). This reflects both its key role in many cell
      functions and its involvement in disease states such as cancers. The best
      understood targets for mTOR signalling are proteins involved in controlling the
      translational machinery, including the ribosomal protein S6 kinases and proteins
      that regulate the initiation and elongation phases of translation. Indeed, there
      is compelling evidence that at least one of these targets of mTOR (eukaryotic
      initiation factor eIF4E) plays a key role in tumorigenesis. It is regulated
      through the mTOR-dependent phosphorylation of inhibitory proteins such as eIF4E
      binding protein 1. Thus, targeting mTOR signalling may be an effective anticancer
      strategy, in at least a significant subset of tumours. Not all effects of mTOR
      are sensitive to the classical anti-mTOR drug rapamycin, and this compound also
      interferes with other processes besides eIF4E function. Developing new approaches
      to targeting mTOR for cancer therapy requires more detailed knowledge of
      signalling downstream of mTOR. Such advances are likely to come from further work
      to understand the regulation of mTOR targets such as components of the
      translational apparatus.

PMID- 17041628
TI  - mTOR and cancer therapy.
AB  - Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of
      the targets of the mTOR kinase, are overexpressed or mutated in cancer.
      Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of
      recently developed rapamycin analogs (rapalogs) consisting of synthetically
      derived compounds containing minor chemical modifications to the parent
      structure, inhibit the growth of cell lines derived from multiple tumor types in
      vitro, and tumor models in vivo. Results from clinical trials indicate that the
      rapalogs may be useful for the treatment of subsets of certain types of cancer.
      The sporadic responses from the initial clinical trials, based on the hypothesis
      of general translation inhibition of cancer cells are now beginning to be
      understood owing to a more complete understanding of the dynamics of mTOR
      regulation and the function of mTOR in the tumor microenvironment. This review
      will summarize the preclinical and clinical data and recent discoveries of the
      function of mTOR in cancer and growth regulation.

PMID- 17041629
TI  - The type III secretion injectisome.
AB  - The type III secretion injectisome is a complex nanomachine that allows bacteria
      to deliver protein effectors across eukaryotic cellular membranes. In recent
      years, significant progress has been made in our understanding of its structure,
      assembly and mode of operation. The principal structural components of the
      injectisome, from the base located in the bacterial cytosol to the tip of the
      needle protruding from the cell surface, have been investigated in detail. The
      structures of several constituent proteins were solved at the atomic level and
      important insights into the assembly process have been gained. However, despite
      the ongoing concerted efforts of molecular and structural biologists, the role of
      many of the constituent components of this nanomachine remain unknown.

PMID- 17041630
TI  - Bacterial populations as perfect gases: genomic integrity and diversification
      tensions in Helicobacter pylori.
AB  - Microorganisms that persist in single hosts face particular challenges.
      Helicobacter pylori, an obligate bacterial parasite of the human stomach, has
      evolved a lifestyle that features interstrain competition and intraspecies
      cooperation, both of which involve horizontal gene transfer. Microbial species
      must maintain genomic integrity, yet H. pylori has evolved a complex nonlinear
      system for diversification that exists in dynamic tension with the mechanisms for
      ensuring fidelity. Here, we review these tensions and propose that they create a
      dynamic pool of genetic variants that is sufficiently genetically diverse to
      allow H. pylori to occupy all of the potential niches in the stomach.

PMID- 17041631
TI  - Viruses of the Archaea: a unifying view.
AB  - DNA viruses of the Archaea have highly diverse and often exceptionally complex
      morphotypes. Many have been isolated from geothermally heated hot environments,
      raising intriguing questions about their origins, and contradicting the
      widespread notion of limited biodiversity in extreme environments. Here, we
      provide a unifying view on archaeal viruses, and present them as a particular
      assemblage that is fundamentally different in morphotype and genome from the DNA
      viruses of the other two domains of life, the Bacteria and Eukarya.

PMID- 17041632
TI  - The silent path to thousands of merozoites: the Plasmodium liver stage.
AB  - Plasmodium sporozoites are deposited in the skin of their vertebrate hosts
      through the bite of an infected female Anopheles mosquito. Most of these
      parasites find a blood vessel and travel in the peripheral blood circulation
      until they reach the liver sinusoids. Once there, the sporozoites cross the
      sinusoidal wall and migrate through several hepatocytes before they infect a
      final hepatocyte, with the formation of a parasitophorous vacuole, in which the
      intrahepatic form of the parasite grows and multiplies. During this period, each
      sporozoite generates thousands of merozoites. As the development of Plasmodium
      sporozoites inside hepatocytes is an obligatory step before the onset of disease,
      understanding the parasite's requirements during this period is crucial for the
      development of any form of early intervention. This Review summarizes our current
      knowledge on this stage of the Plasmodium life cycle.

PMID- 17041634
TI  - Reduced-intensity conditioning allogeneic stem cell transplantation: hype,
      reality or time for a rethink?

PMID- 17041633
TI  - Genomics meets HIV-1.
AB  - Genomics is now a core element in the effort to develop a vaccine against HIV-1.
      Thanks to unprecedented progress in high-throughput genotyping and sequencing, in
      knowledge about genetic variation in humans, and in evolutionary genomics, it is
      finally possible to systematically search the genome for common genetic variants
      that influence the human response to HIV-1. The identification of such variants
      would help to determine which aspects of the response to the virus are the most
      promising targets for intervention. However, a key obstacle to progress remains
      the scarcity of appropriate human cohorts available for genomic research.

PMID- 17041635
TI  - Difference between hematological malignancy and solid tumor research articles
      published in four major medical journals.

PMID- 17041636
TI  - Towards defining the lymphoma methylome.

PMID- 17041637
TI  - Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia.
AB  - The cells of solid tumours are known to have an altered metabolism, with high
      rates of glucose uptake and glycolysis, which results in the excessive production
      of lactate. To date there has been no definitive research documenting metabolic
      changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate
      whether ALL cells have an altered metabolism, we initially compared the
      transcriptional profiles of 22 specimens from paediatric patients diagnosed with
      ALL to five CD34+ specimens isolated from bone marrow, which was verified in an
      independent cohort of 101 specimens. Profiling revealed the upregulation of genes
      facilitating glycolysis in the ALL specimens compared to the CD34+ specimens,
      while those involved in the tricarboxylic acid cycle were downregulated.
      Functional studies supported the microarray findings threefold: (1) higher
      expression of the glucose transport protein glucose transporter 1 in ALL compared
      to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and
      (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose.
      While metabolic alterations have been well documented in solid tumours, this is
      the first study to provide direct evidence for the existence of metabolic changes
      in the leukaemic cells of ALL patients. The finding offers new options for
      targeted therapy for ALL patients.

PMID- 17041639
TI  - Rapid and sensitive typing of NPM1 mutations using LNA-mediated PCR clamping.

PMID- 17041638
TI  - Characterization of an artificial antigen-presenting cell to propagate cytolytic
      CD19-specific T cells.

PMID- 17041640
TI  - Estimation of the power scintillation probability density function in free-space
      optical links by use of multicanonical Monte Carlo sampling.
AB  - Free-space optics (FSO) can provide cost-effective, high-bandwidth, wireless
      connections. However, atmospheric turbulence may degrade the performance of FSO
      links by causing intensity and power scintillations at the receiver.
      Multicanonical Monte Carlo sampling is used in conjunction with the phase screen
      method to calculate the statistics, and particularly the probability density
      function (PDF), of the power fluctuations at an FSO receiver. This allows the
      efficient calculation of the PDF even for very small values with a limited number
      of iterations. The obtained PDF can be used to characterize the performance of
      the system in terms of the error probability.

PMID- 17041641
TI  - Rotational frequency shifts for electromagnetic fields of arbitrary states of
      coherence and polarization.
AB  - The rotational frequency shift is studied for fields of arbitrary states of
      coherence and polarization. It is shown that the power spectrum of the field in
      the rotating frame is influenced both by the degree of polarization and the
      degree of coherence. Examples for some model field classes are given.

PMID- 17041642
TI  - Optical ultrawideband monocycle pulse generation based on cross-gain modulation
      in a semiconductor optical amplifier.
AB  - A novel method for generating ultrawideband (UWB) monocycle pulses based on cross
      gain modulation (XGM) in a semiconductor optical amplifier (SOA) is proposed and
      experimentally demonstrated. Thanks to the XGM in the SOA, a pair of polarity
      reversed optical Gaussian pulses is generated at the output of the SOA, to which
      a Gaussian pulse pump and a continuous-wave probe are applied. The two polarity
      reversed optical pulses are then time delayed by two cascaded fiber Bragg
      gratings to introduce a time delay difference. A UWB monocycle pulse with a full
      width at half-maximum of 48 ps and a fractional bandwidth of 188% is generated at
      the output of a high-speed photodetector.

PMID- 17041643
TI  - Raman response function for silica fibers.
AB  - The commonly used Lorentzian form of the Raman response function for studying
      propagation of ultrashort pulses in silica fibers does not properly account for
      the shoulder in the Raman gain spectrum originating from the Boson peak. We
      propose a more accurate form of this response function and show that its
      predictions for the Raman-induced frequency shift should be in better agreement
      with experiments.

PMID- 17041644
TI  - Absorption as a selective mechanism in surface plasmon resonance fiber optic
      sensors.
AB  - A new concept of surface plasmon resonance fiber optic sensor is presented. By
      tuning the plasmon resonance to a wavelength for which the outer medium is
      absorptive, a significant variation of the spectral transmittance of the device
      is produced as a function of the concentration of the analyte. With this
      mechanism, selectivity can be achieved without the need of any functionalization
      of the surfaces or the use of recognizing elements, which is a very interesting
      feature for any kind of chemical sensor or biosensor. Doubly deposited uniform
      waist tapered fibers are well suited for the development of these new sensors.
      Multiple surface plasmon resonance, obtainable in those structures, can be used
      for the development of microspectrometers based on this principle.

PMID- 17041645
TI  - Slowing down of solitons by intrapulse Raman scattering in fibers with frequency
      cutoff.
AB  - A method for transforming fast solitons into slow ones in bandgap fibers is
      proposed. The approach is based on the deceleration of the solitons by intrapulse
      Raman scattering, which can be achieved for fiber modes having a cutoff
      frequency. We develop a comprehensive theory for the soliton slowdown and
      elucidate how the fiber losses introduce a fundamental minimum for the soliton
      velocity.

PMID- 17041646
TI  - Submicrometer digital in-line holographic microscopy at 32 nm with high-order
      harmonics.
AB  - Soft-x-ray digital in-line microscopic holography is achieved using a fully
      coherent high-order harmonic source emitting at 32 nm. Combination of commercial
      grade soft-x-ray optics and a back-illuminated CCD detector allows a compact and
      versatile holographic setup. Different experimental geometries have been tested
      by imaging calibrated 50 nm tips and 1 microm wires. Spatial resolution of 800 nm
      is measured with magnifications ranging from 30 to 110 and a numerical aperture
      around 0.01. Finally, the potentiality of three-dimensional numerical
      reconstruction from a single hologram acquisition is shown experimentally.

PMID- 17041647
TI  - Spectrally resolved phase-shifting interferometry for accurate group-velocity
      dispersion measurements.
AB  - We report an accurate method to measure the group-velocity dispersion (GVD) of
      transparent materials by use of spectrally resolved phase-shifting
      interferometry. The GVD of silica glass slide measured using an eight-step phase
      shifting algorithm agrees well with that calculated using the Sellmeier
      dispersion equation over the entire visible wavelength region, with a rms error
      of < or =0.0036 microm(-2), better than that of other measurement methods
      reported so far.

PMID- 17041648
TI  - Frequency-comb-referenced two-wavelength source for absolute distance
      measurement.
AB  - We propose a new tunable laser source concept for multiple-wavelength
      interferometry, offering an unprecedented large choice of synthetic wavelengths
      with a relative uncertainty better than 10(-11) in vacuum. Two lasers are
      frequency stabilized over a wide range of frequency intervals defined by the
      frequency comb generated by a mode-locked fiber laser. In addition, we present
      experimental results demonstrating the generation of a 90 mum synthetic
      wavelength calibrated with an accuracy better than 0.2 parts in 10(6). With this
      synthetic wavelength we can resolve one optical wavelength, which opens the way
      to absolute distance measurement with nanometer accuracy.

PMID- 17041649
TI  - Polarization beam splitter based on a photonic crystal heterostructure.
AB  - The design and characterization of a photonic crystal (PC) polarization beam
      splitter (PBS) that operates with an extinction ratio of greater than 15 dB for
      both polarizations are presented. The PBS is fabricated on a silicon-on-insulator
      (SOI) wafer where the input and output ports consist of 5 mum wide ridge
      waveguides. A large spectral shift is observed in the dispersion plots of the
      lowest-order even (TE-like) and odd (TM-like) modes due to the SOI confinement.
      Because of this shift, the TE-like mode is close to a directional gap at the top
      of the band, and the TM-like mode is in a low-frequency regime where the
      dispersion surface is almost isotropic. We show that the TE-like mode has very
      high reflection at the interface between the two PCs, whereas the TM-like mode
      exhibits a very high transmission.

PMID- 17041650
TI  - Simultaneous achievement of narrow pulse width and low pulse-to-pulse timing
      jitter in 1.3 microm passively mode-locked quantum-dot lasers.
AB  - We have analyzed pulse width and timing jitter in passively mode-locked two
      section InAs quantum-dot lasers emitting at 1310 nm and have identified two
      distinct, extensive mode-locked regions with robust short pulses and low timing
      jitter. A record combination of 2 ps pulses and 25 fs/cycle timing jitter (500
      fs, 1-100 MHz), with 1 mW average output power per facet, is demonstrated.

PMID- 17041651
TI  - Expedited laser damage profiling of KDxH(2-x)PO4 with respect to crystal growth
      parameters.
AB  - We investigate the laser-induced damage resistance at 355 nm in deuterated
      potassium dihydrogen phosphate (DKDP) crystals grown with varying growth
      parameters, including speed of growth and temperature. The aim is to explore a
      new expedited method to study the growth parameters affecting the laser-induced
      damage resistance in DKDP material to obtain crystals with enhanced performance.

PMID- 17041652
TI  - Carrier-envelope phase shift caused by variation of grating separation.
AB  - The effects of variation of the grating separation in a stretcher on the carrier
      envelope (CE) phase of amplified pulses are investigated. By translating one of
      the telescope mirrors in the stretcher with a piezoelectric transducer, it is
      found that a 1 mum change of the distance causes a 3.7+/-1.2 rad shift of the CE
      phase, which is consistent with theoretical estimations. The results indicate
      that optical mounts used for gratings and telescope mirrors must be
      interferometrically stable; otherwise their vibration and thermal drift will
      cause significant phase error. The CE phase drift was corrected by feedback
      controlling the grating separation.

PMID- 17041653
TI  - 110 W double-ended ytterbium-doped fiber superfluorescent source with M2 = 1.6.
AB  - High-power operation of a broadband superfluorescent fiber source has been
      achieved via the process of amplified spontaneous emission (ASE) in a double-clad
      Yb-doped multimode-offset-core fiber by using a novel fiber-end termination
      geometry to suppress lasing. The fiber was cladding pumped by a high-power diode
      source at 976 nm and yielded a maximum ASE output of 63 and 47 W from the two
      ends of the fiber, respectively. The maximum combined ASE output was 110 W with
      slope efficiency with respect to launched pump power of up to 68%. The wavelength
      spectrum of the ASE source spanned the range from approximately 1032 to 1120 nm,
      and the bandwidth (FWHM) of the emission spectrum was 40 nm. The output beam was
      slightly multimode with a beam-quality factor (M2) of 1.6. The prospects for
      further improvement in performance are considered.

PMID- 17041655
TI  - Sensing cell metabolism by time-resolved autofluorescence.
AB  - We built a time-resolved confocal fluorescence spectroscopy system equipped with
      the multichannel time-correlated single-photon-counting technique. The instrument
      provides a unique approach to study the fluorescence sensing of cell metabolism
      via analysis of the wavelength- and time-resolved intracellular autofluorescence.
      The experiments on monolayered cell cultures show that with UV excitation at 365
      nm the time-resolved autofluorescence decays, dominated by free-bound reduced
      nicotinamide adenine dinucleotide signals, are sensitive indicators for cell
      metabolism. However, the sensitivity decreases with the increase of excitation
      wavelength possibly due to the interference from free-bound flavin adenine
      dinucleotide fluorescence. The results demonstrate that time-resolved
      autofluorescence can be potentially used as an important contrast mechanism to
      detect epithelial precancer.

PMID- 17041654
TI  - Assessing epithelial cell nuclear morphology by using azimuthal light scattering
      spectroscopy.
AB  - We describe azimuthal light scattering spectroscopy (phi/LSS), a novel technique
      for assessing epithelial-cell nuclear morphology. The difference between the
      spectra measured at azimuthal angles phi = 0 degrees and phi = 90 degrees
      preferentially isolates the single backscattering contribution due to large
      (approximately 10 microm) structures such as epithelial cell nuclei by
      discriminating against scattering from smaller organelles and diffusive
      background. We demonstrate the feasibility of using phi/LSS for cancer detection
      by showing that spectra from cancerous colon tissue exhibit significantly greater
      azimuthal asymmetry than spectra from normal colonic tissues.

PMID- 17041656
TI  - Polychromatic interface solitons in nonlinear photonic lattices.
AB  - We demonstrate that interfaces between two nonlinear periodic photonic lattices
      offer unique possibilities for controlling the nonlinear interaction between
      different spectral components of polychromatic light, and a change in the light
      spectrum can have a dramatic effect on the propagation along the interface. We
      predict the existence of polychromatic surface solitons that differ fundamentally
      from their counterparts in infinite lattices.

PMID- 17041657
TI  - BiB3O6 femtosecond optical parametric oscillator.
AB  - We report a femtosecond optical parametric oscillator (OPO) based on the
      nonlinear material BiB3O6. The OPO is synchronously pumped in the blue by the
      second harmonic of a Kerr-lens-mode-locked Ti:sapphire laser. It can provide wide
      and continuous tuning across the entire green-yellow-orange-red spectral range
      with a single crystal and a single set of mirrors. Using a 500 microm BiB3O6
      crystal and collinear type I (e+e->o) phase matching in the optical yz plane, a
      signal wavelength range of 480-710 nm is demonstrated with angle tuning at room
      temperature at average output powers of 270 mW. With 220 fs blue pump pulses,
      near-transform-limited signal pulses of 120 fs duration have been obtained at 76
      MHz repetition rate.

PMID- 17041658
TI  - Chaotic stimulated Brillouin scattering near the threshold in a fiber.
AB  - We investigate the nonlinear dynamic behavior of stimulated Brillouin scattering
      (SBS) near threshold in the absence of feedback. When a cw Nd:YAG laser is
      injected into a single-mode optical fiber, the SBS signal exhibits intermittently
      appearing irregular self-pulsations near the threshold. By examining the time
      series of the SBS signals, we verify that the irregular SBS signal is one of the
      chaotic phenomena appearing near the bifurcation point.

PMID- 17041659
TI  - Planar-waveguide quasi-phase-matched second-harmonic-generation device in Y-cut
      MgO-doped LiNbO3.
AB  - We designed a planar-waveguide quasi-phase-matched second-harmonic-generation
      device, which consists of a Y-cut periodically poled 5 mol.% MgO-doped LiNbO3
      core and SiO2 claddings, that provided a 1.08 W green light with 30% conversion
      efficiency by using a 7 mm long sample at room temperature. The highest
      conversion efficiency of 49% at 0.88 W second-harmonic generation was attained by
      using an 18 mm long device.

PMID- 17041660
TI  - Vector soliton switching by using the cascade connection of saturable absorbers.
AB  - We have numerically studied the cascade connection of a nonlinear amplifying loop
      mirror and a length of birefringent fiber with two linear polarizers. This
      structure is shown to work as a vector soliton switch under certain conditions.
      After optimizing each structure separately, we show the improvement of the
      switching response when the cascade connection is used. It is also demonstrated
      that this design acts as a good intensity filter for vector soliton pulses.

PMID- 17041661
TI  - Silicon waveguides for creating quantum-correlated photon pairs.
AB  - We propose to use four-wave mixing inside silicon waveguides for generating
      quantum-correlated photon pairs in a single spatial mode. Such silicon-based
      photon sources not only exhibit high pair correlation but also have high spectral
      brightness. As the proposed scheme is based on mature silicon technology, it has
      the potential of becoming a cost-effective platform for on-chip quantum
      information processing applications.

PMID- 17041662
TI  - Nonlinear mirror based on cross-polarized wave generation.
AB  - We present a new type of nonlinear mirror based on the generation of a cross
      polarized wave through a nonresonant electronic third-order process. It is
      characterized by a reflection coefficient that depends on the input intensity.
      Its behavior results from the interference between the nonlinearly generated
      cross-polarized wave and a pi/2 phase-retarded wave. This setup has a lot of
      advantages: it does not require any phase matching, it is achromatic and suitable
      for femtosecond pulses, linear losses are easily adjustable, and the overall
      behavior is predictable. The device has been experimentally tested using BaF2 and
      YVO4 crystals.

PMID- 17041663
TI  - Quadratic phase matching in slot waveguides.
AB  - We analyze phase matching with reference to frequency doubling in nanosized
      quadratic waveguides encompassing form birefringence and supporting cross
      polarized fundamental and second-harmonic modes. In an AlGaAs rod with an air
      void, we show that phase-matched second-harmonic generation could be achieved in
      a wide spectral range employing state-of-the-art nanotechnology.

PMID- 17041664
TI  - 52 mJ narrow-bandwidth degenerated optical parametric system with a large
      aperture periodically poled MgO:LiNbO3 device.
AB  - We have demonstrated efficient, high-energy, narrow-spectral-bandwidth 2.128
      microm pulse generation by use of periodically poled MgO:LiNbO3 devices with a 36
      mm length and a 5 mm x 5 mm large aperture. A free-running degenerated optical
      parametric oscillator (OPO) pumped with a Q-switched 1.064 microm Nd:YAG laser
      exhibits a high slope efficiency of 75% and an optical-to-optical conversion
      efficiency of 70% with a broad spectral bandwidth (>100 nm). In a configuration
      with a spectrally narrowed master oscillator followed by a power amplifier, we
      have achieved an output pulse energy of 52 mJ with a spectral bandwidth of less
      than 2 nm at the degeneracy point. The total optical-to-optical conversion
      efficiency of the system reached 50%.

PMID- 17041665
TI  - Effect of photonic crystal structure on the nonlinear optical anisotropy of
      birefringent porous silicon.
AB  - Anisotropic photonic crystal structures consisting of birefringent porous silicon
      layers with alternating porosity were fabricated. The in-plane birefringence
      formed as a result of anisotropic etching in Si(110) results in unique
      multilayered structures with two distinct photonic bandgaps for orthogonal light
      polarizations. Nonlinear optical studies based on the third-harmonic generation
      from these structures demonstrate variation in the symmetry of the nonlinear
      optical response.

PMID- 17041666
TI  - Multiscale Bessel beams generated by a tunable acoustic gradient index of
      refraction lens.
AB  - A beam that resembles a Bessel beam on two scales is generated using a tunable
      acoustic gradient index of refraction (TAG) lens. The minor scale of the TAG
      generated Bessel beam is nondiffracting and self-healing. The major scale of the
      beam diffracts while still forming a Bessel pattern due to the specific geometry
      of the TAG lens. The acoustic and optical theory behind the TAG lens is outlined,
      and the experimental beam itself is presented. The major and minor rings are
      explained, and the TAG beam is compared with both axicon-generated and
      conventionally focused Gaussian beams.

PMID- 17041667
TI  - Three-level phase modulator based on orthoconic antiferroelectric liquid
      crystals.
AB  - Surface-stabilized orthoconic antiferroelectric liquid crystals (OAFLCs) have a
      director tilt of theta = 45 degrees and are, with no field applied, negatively
      uniaxial with the optic axis perpendicular to the cell substrates. We demonstrate
      that OAFLCs can be utilized to achieve lossless phase modulation with three
      almost equidistant phase levels. This turns out to be true also for polymer
      stabilized OAFLCs, where the polymer network increases the switching speed of the
      device without affecting the phase modulation appreciably.

PMID- 17041668
TI  - Slanted hole array beam profiler (SHArP)-a high-resolution portable beam profiler
      based on a linear aperture array.
AB  - We demonstrate a novel high-resolution portable beam profiler based on a slanted
      linear array of small apertures, termed a slanted hole array beam profiler
      (SHArP). The apertures are directly fabricated on a metal-coated CMOS imaging
      sensor. With a single linear scan, the aperture array can establish a virtual
      grid of sampling points for beam profiling. With our prototype, we demonstrate
      beam profiling of Gaussian beams over an area of 66.5 microm x 66.5 microm with a
      resolution of 0.8 microm (compare with the CMOS pixel size of 10 microm). The
      resolution can be improved into the range of submicrometers by fabricating
      smaller apertures. The good correspondence between the measured and calculated
      beam profiles proves the fidelity of our new beam profiling scheme.

PMID- 17041669
TI  - Tunable two-dimensional hexagonal phase array in domain-engineered Z-cut lithium
      niobate crystal.
AB  - An optical phase array with tunable phase step is demonstrated. The phase array
      consists of a two-dimensional hexagonal lattice of inverted ferroelectric domains
      fabricated on a Z-cut lithium niobate substrate. The electro-optically tunable
      phase step is obtained by the application of an external electric field along the
      z axis of the crystal via transparent electrodes. Theoretical analysis and
      experimental results are presented, showing that a tunable and flexible adaptive
      optical illuminator device can be realized by combining the electro-optic
      tunability with the Talbot effect. Generation of a multiplicity of light patterns
      is shown.

PMID- 17041670
TI  - Optical detection of the Casimir force between macroscopic objects.
AB  - We report the optical detection of mechanical deformation of a macroscopic object
      induced by the Casimir force. An adaptive holographic interferometer based on a
      photorefractive BaTiO3:Co crystal was used to measure periodical nonlinear
      deformations of a thin pellicle caused by an oscillating Casimir force. A
      reasonable agreement between the experimental and calculated values of the first
      and second harmonics of the Casimir force oscillations has been obtained.

PMID- 17041672
TI  - Giant enhancement of band edge emission in ZnO and SnO nanocomposites.
AB  - ZnO/SnO nanocomposites have been designed to enhance the band edge emission and
      suppress the defect emission of ZnO nanorods simultaneously. It is found that the
      intensity ratio between the band edge and defect emission can be improved by up
      to 4 orders of magnitude. The underlying mechanism is interpreted in terms of
      surface modification as well as carrier transfer from SnO nanoparticles to ZnO
      nanorods. Our approach is very useful for creating highly efficient
      optoelectronic devices.

PMID- 17041671
TI  - CO and CO2 spectroscopy using a 60 nm broadband tunable MEMS-VCSEL at
      approximately 1.55 microm.
AB  - The spectroscopic application of a new broadband microelectromechanical-system
      tunable vertical cavity surface-emitting laser with single-mode coverage of 60 nm
      (245 cm(-1)) in a single, continuous sweep is described. The operation of the
      device is illustrated with high-resolution spectra of CO and CO2 over 110 cm(-1)
      (27 nm) and 67 cm(-1) (17 nm), respectively, with the CO band shown for high
      pressure scans between 1 and 3 bars (0.1-0.3 MPa). The achieved tuning range
      opens up new opportunities for tunable diode laser absorption spectroscopy. The
      spectra were compared with HITRAN-derived model calculations. The benefits of a
      sensor based on this laser are greater speed, laser power, and tuning range.

PMID- 17041673
TI  - Sensitive femtosecond coherent anti-Stokes Raman spectroscopy discrimination
      between dipicolinic acid and dinicotinic acid.
AB  - We demonstrate that femtosecond ultraviolet and visible coherent anti-Stokes
      Raman spectroscopy provides the sensitivity and specificity needed to distinguish
      between two similar molecules of pyridinedicarboxylic acid. The Fourier
      transforms of the temporal measurements provide the energy difference between the
      ground state vibrational modes. Quantum chemical calculations provide theoretical
      predictions that agree well with the measurements. The present technique allows
      us to distinguish 10 cm(-1) frequency shifts by using pulses ten times broader
      than the shifts.

PMID- 17041674
TI  - Continuous-wave frequency comb Fourier transform source based on a high
      dispersion cavity.
AB  - A dispersive grating compressor was included in a fiber ring laser to generate an
      unequally spaced frequency comb spanning approximately 1549-1552 nm. Beating of
      nearby modes in the comb naturally assigns unique amplitude modulation
      frequencies to each spectral component emitted. The source contains no moving
      parts. The single-mode fiber-coupled output is directed through hydrogen cyanide
      gas and detected by a photodiode. A Fourier transform of a 1 ms record yields a
      spectrum that agrees with results from a grating spectrometer at 0.06 nm
      resolution. By engineering stable, broadband combs, the technique could result in
      a universal and simple approach for spectroscopy at almost arbitrary measurement
      speeds and spectral resolutions limited only by Fourier principles.

PMID- 17041675
TI  - Spectral line-shape measurement of an extremely weak amplitude-fluctuating light
      source by photon-counting-based second-order correlation spectroscopy.
AB  - We demonstrate line-shape measurement of an extremely weak amplitude-fluctuating
      light source by using photon-counting-based second-order correlation spectroscopy
      combined with the heterodyne technique. The amplitude fluctuation of a finite
      bandwidth introduces a low-lying spectral structure in the line shape, and thus
      its effect can be isolated from that of the phase fluctuation. Our technique
      provides extreme sensitivity suited for single-atom-level applications.

PMID- 17041676
TI  - Generation of 11 fs pulses by using hollow-core gas-filled fibers at a 100 kHz
      repetition rate.
AB  - Using self-phase modulation in a hollow-core fiber filled with xenon, we were
      able to produce 2.3 microJ laser pulses with a duration of 10.9 fs at a
      repetition rate of up to 100 kHz. We started with 45 fs, 4.4 microJ, 800 nm
      pulses generated by a Coherent RegA Ti:sapphire regenerative amplifier system,
      then spectrally broadened the 30 nm bandwidth to more than 100 nm. Dispersion
      compensation was achieved with two pairs of chirped mirrors. This is believed to
      be the first time this type of compression was achieved at a repetition rate as
      high as 100 kHz. This brings the advantages of few-cycle laser pulses to
      experiments that require high-repetition-rate, low-energy laser systems, for
      example, coincidence experiments.

PMID- 17041677
TI  - Generating single attosecond pulses via spatial filtering.
AB  - The first observation of isolated attosecond pulses by Hentschel [Nature 414, 509
      (2001)] resulted from an experiment that left the exact mechanism of their
      generation unresolved. A complete simulation of the experiment reveals the reason
      for its success: single pulses were efficiently isolated from two or more
      generated pulses by spatial filtering in the far field. Our explanation suggests
      a new, simple paradigm for the production of isolated attosecond bursts. We show
      that this method can be used, in conjunction with carrier-envelope phase
      stabilization, to select single attosecond pulses by use of 10 fs driving pulses.

PMID- 17041678
TI  - Propagation of femtosecond pulses in large-mode-area, higher-order-mode fiber.
AB  - We demonstrate propagation of 14 nJ femtosecond pulses through a large-mode-area,
      higher-order-mode (HOM) fiber with an effective area of 2100 microm2. The pulses
      propagate stably in the LP07 mode of the fiber through lengths as long as 12 m.
      The strongly chirped pulses exiting the amplifier fiber are dechirped by the high
      order-mode fiber, resulting in pulses with a peak power of 61 kW after
      propagation in 5 m of the positive-dispersion fiber. A small amount of self-phase
      modulation is observed in the compressed pulses and is described well by a
      nonlinear Schrodinger equation model that takes into account the measured
      effective area and dispersion of the HOM fiber.

PMID- 17041679
TI  - Crystal optics as guard apertures for coherent x-ray diffraction imaging.
AB  - A crucial issue in coherent x-ray diffraction imaging experiments is how to
      increase the signal-to-noise ratio when measuring relatively weak diffraction
      intensities from a nonperiodic object. A novel crystal guard aperture is
      described that makes use of a pair of multiple-bounce crystal optics to eliminate
      unwanted parasitic scattering background. This background is often produced by
      upstream optical elements such as a coherent-beam defining aperture. Recent
      experimental observation and theoretical analysis confirm the effectiveness of
      the crystal guard aperture method with coherence-preserved wave propagation
      through the crystal guard aperture and dramatically reduced scattering background
      in coherent x-ray diffraction images.

PMID- 17041680
TI  - What do practitioners think? A qualitative study of a shared care mental health
      and nutrition primary care program.
AB  - OBJECTIVE: To develop an in-depth understanding of a shared care model from
      primary mental health and nutrition care practitioners with a focus on program
      goals, strengths, challenges and target population benefits. DESIGN: Qualitative
      method of focus groups. SETTING/PARTICIPANTS: The study involved fifty-three
      practitioners from the Hamilton Health Service Organization Mental Health and
      Nutrition Program located in Hamilton, Ontario, Canada. METHOD: Six focus groups
      were conducted to obtain the perspective of practitioners belonging to various
      disciplines or health care teams. A qualitative approach using both an editing
      and template organization styles was taken followed by a basic content analysis.
      MAIN FINDINGS: Themes revealed accessibility, interdisciplinary care, and complex
      care as the main goals of the program. Major program strengths included
      flexibility, communication/collaboration, educational opportunities, access to
      patient information, continuity of care, and maintenance of practitioner and
      patient satisfaction. Shared care was described as highly dependent on
      communication style, skill and expertise, availability, and attitudes toward
      shared care. Time constraint with respect to collaboration was noted as the main
      challenge. CONCLUSION: Despite some challenges and variability among practices,
      the program was perceived as providing better patient care by the most
      appropriate practitioner in an accessible and comfortable setting.

PMID- 17041681
TI  - Of clamps, clips, and computers.

PMID- 17041682
TI  - Myotrophin/V-1 does not act as an extracellular signal to induce myocyte
      hypertrophy.
AB  - The myotrophin/V-1 protein was originally found to be elevated in failing heart
      tissues and was described as an exogenously acting hypertrophy-inducing factor.
      However, several studies have proposed only intracellular functions for this
      protein. We investigated whether this protein is an exogenously acting
      hypertrophy-inducing trophin or an intracellular nuclear factor of kappa B
      (NFkappaB) regulatory protein. In the current report, immunofluorescence and cell
      fractionation studies showed that myotrophin is present only in the cytoplasm and
      is not actively released into the extracellular environment in response to
      hypertrophy-inducing stimuli. Moreover, in response to ischemia/reperfusion
      injury, an active release of myotrophin from adult rat myocardium was not
      observed. Furthermore, protein synthesis studies in rat neonatal myocytes
      indicated that exogenous myotrophin did not induce hypertrophy. On the other
      hand, myotrophin stimulates the generation of NFkappaB dimers in vitro and thus
      regulates the NFkappaB-mediated transcription in cardiac myocytes. Taken
      together, these studies suggest that myotrophin is a strictly cytosolic protein
      that regulates the NFkappaB-mediated transcriptional process.

PMID- 17041683
TI  - A simple and fast experimental model of myocardial infarction in the mouse.
AB  - In this report, we describe a simple and fast method for creating a murine
      myocardial infarction model and providing a useful and convenient tool for the
      research in ischemic heart disease. We established acute myocardial infarction in
      the Kunming-strain mouse within 2 minutes by ligating the left anterior
      descending coronary artery. The model was evaluated by observing the changes in
      histology and in the serum levels of aspartate aminotransferase and lactate
      dehydrogenase. Obvious myocardial necrosis was found in the 24-hr experimental
      (ligation) group. The average size of the infarction was 44.3% +/- 2.9% of the
      left ventricle. Serum levels of aspartate aminotransferase and lactate
      dehydrogenase reached their peak in the 24-hr experimental group and were normal
      in the 72-hr experimental group. We set forth a simple and quick method for
      producing acute myocardial infarction experimentally in the mouse. The model can
      be reproduced in a stable manner, under experimental conditions that are easy to
      duplicate.

PMID- 17041684
TI  - Nitric oxide, endothelin-1, and superoxide production in arterial bypass grafts.
AB  - In this study, basal and thrombin-stimulated release of nitric oxide and
      endothelin-1 in the internal mammary artery and the radial artery were measured,
      together with superoxide radicals generated after anoxia and reoxygenation.
      Arterial segments were obtained from patients undergoing coronary bypass
      operations. Quantification of nitric oxide was performed by measuring the stable
      oxidation products of nitric oxide. Endothelin levels were measured by an enzyme
      immunoassay kit, and the superoxides were measured by lucigenin-enhanced
      chemiluminescence. Basal and stimulated release of nitric oxide from the internal
      mammary artery is significantly higher than that in the radial artery. On the
      other hand, basal release of endothelin-1 is less in the internal mammary artery
      than in the radial artery, but similar after stimulation. In our study, the
      quantity of superoxide radicals produced by the internal mammary artery was
      greater than that produced by the radial artery. Our results show that there are
      differences between these 2 arteries in regard to production of nitric oxide,
      endothelin-1, and superoxide radicals. These differences may have a role in the
      process of atherogenesis and may contribute to long-term patency of arterial
      bypass grafts. These results may also explain the mechanism of radial artery
      graft spasm in coronary artery surgery and may constitute a basis for future
      pharmacological and clinical improvements for successful surgical application.

PMID- 17041685
TI  - Lowest hematocrit on cardiopulmonary bypass impairs the outcome in coronary
      surgery: An Italian Multicenter Study from the National Cardioanesthesia
      Database.
AB  - Severe hemodilutional anemia on cardiopulmonary bypass increases morbidity and
      mortality after coronary surgery. The present study focuses on the lowest
      hematocrit values during extracorporeal circulation and on allogenic blood
      transfusions as mortality and morbidity risk factors. The records of 1,766
      consecutive adult patients undergoing isolated coronary artery bypass graft
      surgery at 3 institutions have been analyzed retrospectively for in-hospital
      mortality and adverse outcomes. Clinical data were from the Italian National
      Cardioanesthesia Database. Multivariate analysis and analysis of receiver
      operating characteristic curves were applied. The lowest hematocrit value on
      cardiopulmonary bypass was an independent risk factor for postoperative low
      output syndrome and renal failure. The hematocrit cutoff values were similar for
      renal failure (23%) and low-output syndrome (24%). Blood transfusions were
      significantly associated with both renal failure and low-output syndrome. The
      risk of renal failure doubled when the nadir-on-cardiopulmonary-bypass hematocrit
      occurred in transfused patients. Anemia upon cardiopulmonary bypass was not
      associated with death. Our findings confirm that both severe anemia and blood
      transfusions were significantly associated with renal failure and low-output
      syndrome.

PMID- 17041686
TI  - Open-chest management after heart transplantation.
AB  - Postcardiotomy open-chest management has been widely used in cardiac surgery.
      Although this strategy can be applied to heart transplantation, the use of
      immunosuppressants in transplant recipients raises particular concerns about
      sternal wound infection and impaired healing. We performed a retrospective review
      of 403 patients who had undergone 410 heart transplantations at our institution
      from 1985 through 2004. Among them, 9 patients (2.2%) had open-chest management
      postoperatively. There were 8 men and 1 woman, with a mean age of 58 +/- 7 years.
      The graft ischemic time ranged from 130 to 374 minutes (mean, 218 +/- 99 min),
      and the cardiopulmonary bypass time ranged from 98 to 360 minutes (mean, 210 +/-
      69 min). In all cases, the reason for open-chest management was hemodynamic
      lability that precluded chest closure after transplantation. One patient also
      experienced postoperative bleeding. All patients underwent delayed sternal
      closure between postoperative days 1 and 11 (median, 4 days). Delayed sternal
      closure did not cause any significant hemodynamic changes. One patient died of
      stroke on postoperative day 22. No patient had sternal wound infection or
      impaired wound healing during the follow-up period. We conclude that, when
      required, open-chest management is an effective and safe measure for
      hemodynamically unstable heart transplant patients.

PMID- 17041687
TI  - Direct versus side-graft cannulation of the right axillary artery for antegrade
      cerebral perfusion.
AB  - Antegrade selective cerebral perfusion through the right axillary artery has
      proved to be a safe and effective method for cerebral protection in aortic
      surgery. In this study, we prospectively evaluated the techniques of direct right
      axillary artery cannulation (Group 1) and right axillary artery side-graft
      cannulation (Group 2), investigated cannulation-related complications, and
      determined the hemodynamic advantages and disadvantages of both cannulation
      techniques. Sixty-eight patients underwent surgery from April 2001 through August
      2004 with the diagnoses of ascending and aortic arch aneurysms (10 patients),
      type A aortic dissection (56 patients), and aortic pseudoaneurysm (2 patients).
      There were 22 patients in Group 1 (33.4%) and 46 patients in Group 2 (67.6%). The
      antegrade selective cerebral perfusion flow was 500 to 700 mL/min in Group 1,
      whereas in Group 2 the flow was adjusted in accordance with the mean right radial
      arterial pressure, which was 50 mmHg. There was no significant difference between
      the groups in antegrade selective cerebral perfusion times, but the transient
      neurologic dysfunction rate (4 of 22 patients in Group 1 vs 1 of 42 in Group 2)
      was significantly lower in Group 2 (P =0.035). In Group 1, axillary artery
      dissection occurred in 2 patients (9%), and postoperative arm ischemia occurred
      in 1 patient (4.5%). These complications were not seen in Group 2 (P =0.031). The
      side-graft cannulation technique may be more acceptable because of its lower
      local-complication rate and because it provides pressure-controlled cerebral
      perfusion.

PMID- 17041688
TI  - The transition from open to endoscopic saphenous vein harvesting and its clinical
      impact: The Texas Heart Institute experience.
AB  - Open saphenous vein harvesting can be associated with wound complications,
      incision pain, prolonged convalescence, and poor cosmetic results. Endoscopic
      vein harvesting has been widely used for prevention of these problems. We
      compared outcomes of open and endoscopic vein harvesting for coronary artery
      bypass grafting at the Texas Heart Institute. We retrospectively analyzed data
      from 1,573 consecutive coronary artery bypass procedures performed at our
      institution during a 20-month period. Each procedure included saphenectomy by
      endoscopic vein harvesting (n = 588) performed by physician assistants, or by
      traditional open vein harvesting (n = 985) performed by physicians or physician
      assistants. The primary outcome variable was the incidence of postoperative leg
      infections. Both groups were similar in terms of preoperative risk factors. After
      surgery, leg wound infections were significantly less frequent in the endoscopic
      vein harvesting group (3/588, 0.5%) than in the open vein harvesting group
      (27/985, 2.7%; P < 0.002). The most common organism involved in leg infections
      was Staphylococcus (20/30, 66%): S. aureus was present in 14 of 30 infections
      (47%). Open vein harvesting was the only significant independent risk factor for
      leg infection. We conclude that endoscopic vein harvesting reduces leg wound
      infections, is safe and reliable, and should be the standard of care when venous
      conduits are required for coronary artery bypass grafting and vascular
      procedures. Although the transition from open to endoscopic vein harvesting can
      be challenging in institutions, it can be successful if operators receive
      adequate training in endoscopic technique and are supported by surgeons and
      staff.

PMID- 17041689
TI  - Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump
      comparison by measuring heart-type fatty-acid-binding protein release.
AB  - This prospective study uses heart-type fatty-acid-binding protein (hFABP) and
      creatine kinase-MB (CK-MB) release to compare myocardial injury in on-pump versus
      off-pump coronary artery bypass grafting (CABG). Fifty patients were randomly
      assigned to on-pump or off-pump CABG. The hFABP and CK-MB concentrations were
      measured in serial venous blood samples drawn before heparinization in both
      groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, and 72 hours in the on
      pump group. In the off-pump group, samples were taken after the last distal
      anastomosis at the same time intervals as in the on-pump group. The total amount
      of hFABP and CK-MB released was significantly higher in the on-pump than in the
      off-pump group (hFABP = 100.43 +/- 77.63 vs 3.94 +/- 0.36 ng/mL, P < 0.0001; CK
      MB = 33.33 +/- 3.81 vs 28.65 +/- 3.91 log units, P < 0.001). In all patients,
      hFABP levels peaked as early as 1 hour after declamping (on-pump group) or 2
      hours after the last distal anastomosis (off-pump group), whereas CK-MB peaked
      only at 4 hours after declamping (on-pump group) or 24 hours after the last
      distal anastomosis (off-pump group). The lower release of hFABP and CK-MB in the
      off-pump CABG group indicates that on-pump CABG with cardioplegic arrest causes
      more myocardial damage than does off-pump CABG. Heart-type fatty-acid-binding
      protein is a more rapid marker of perioperative myocardial damage, peaks earlier
      than CK-MB, and may predict the requirement for intensive monitoring for
      postoperative myocardial infarction.

PMID- 17041690
TI  - Experience with the Edwards MIRA mechanical bileaflet valve in the aortic and
      mitral positions.
AB  - The Edwards MIRA bileaflet mechanical prosthesis, a heart valve not yet available
      in the United States, is designed with a unique hinge mechanism, curved leaflets,
      and thin titanium housing. We performed this study to investigate its clinical
      performance and postoperative hemodynamic results. We implanted 58 Edwards MIRA
      prostheses in 51 patients in the aortic (n = 18), mitral (n = 26), and aortic and
      mitral (n = 7) positions. Patients' ages ranged from 25 to 84 years (mean age,
      53.7 +/- 13.6). Operative mortality was 2% (n = 1), and late mortality was 4% (n
      = 2). Thromboembolic events were observed in 2 patients (valve thrombosis in 1
      and a cerebrovascular event in 1). There were no complications related to
      anticoagulation. No signs of valvular dysfunction or paravalvular leakage were
      observed. Peak transvalvular gradients of the aortic prostheses ranged from 24.25
      +/- 5.32 mmHg for the 21-mm valve to 11 +/- 1.41 mmHg for the 25-mm valve. The
      effective orifice area ranged from 1.99 +/- 0.12 cm2 for the 21-mm valve to 2.44
      +/- 0.17 cm2 for the 25-mm valve. The mean transvalvular gradients of the mitral
      prostheses ranged from 5.85 +/- 2.91 mmHg for the 27-mm valve to 4.5 +/- 0 mmHg
      for the 31-mm valve. The effective orifice area ranged from 2.31 +/- 0.03 cm2 for
      the 27-mm valve to 2.64 +/- 0.05 cm2 for the 33-mm valve. These preliminary data
      suggest good hemodynamic function and a low rate of valve-related complications
      in the use of the Edwards MIRA mechanical prosthesis.

PMID- 17041691
TI  - Surgical treatment of cardiac hydatid disease: A report of 7 cases.
AB  - Cardiac echinococcosis is a rare but potentially very serious complication of
      hydatid disease. It is a diagnostic and therapeutic challenge due to the
      variability of signs and symptoms at presentation and to its numerous, often
      unpredictable, preoperative complications. Our clinical experiences with 7 cases
      of cardiac echinococcosis are reported, and the diagnostic and therapeutic
      considerations for the management of patients are discussed, together with a
      review of the literature.

PMID- 17041694
TI  - Cannulation in the diseased aorta: a safe approach using the Seldinger technique.
AB  - The Seldinger technique is a method of femoral cannulation that has been used to
      establish cardiopulmonary bypass. Reports of cannulation of the ascending aorta
      for antegrade perfusion using the Seldinger method are anecdotal. To the best of
      our knowledge, the approach described herein for direct cannulation of the
      ascending aorta with use of the Seldinger technique for antegrade perfusion has
      not been previously described in the English-language medical literature. This
      method is helpful when the surgeon is treating a patient who has a calcified
      ascending aorta, complicated aortic dissection, calcified femoral vessels, or a
      diseased thoracoabdominal aorta. In such cases, retrograde perfusion has been
      associated with severe complications as a result of atheromatous embolization
      from the descending thoracic aorta. Herein, we describe our approach to
      cannulation for cardiopulmonary bypass, which entails insertion of an aortic
      cannula into the ascending aorta by means of the Seldinger technique. A soft-tip
      guidewire is inserted through an arterial entry catheter that has been used to
      puncture a hole in the wall of the vessel. Then the aortic cannula is introduced
      into the vessel, sliding along the guidewire. Guided by transesophageal
      echocardiography, the tip of the cannula is positioned carefully and is then
      advanced into the descending aorta. This positioning of the cannula decreases the
      chance of arterial embolization, thereby improving cerebral protection. If
      cannulation of the ascending aorta is not feasible, the transverse aortic arch or
      proximal descending aorta can be used.

PMID- 17041692
TI  - The cardiomyopathy of iron deficiency.
AB  - Iron-deficiency anemia can have deleterious effects on the heart. Herein, we
      describe the effects of iron deficiency on the heart as corroborated with
      electrocardiography, radiology, echocardiography, and cardiac catheterization. We
      review the pathophysiology, clinical features, and management of iron-deficiency
      induced cardiomyopathy.

PMID- 17041693
TI  - The open-artery hypothesis revisited.

PMID- 17041695
TI  - Alternative surgical strategy for the treatment of a mycotic aortic arch
      aneurysm.
AB  - We report the case of a 69-year-old man who presented with a symptomatic mycotic
      aneurysm of the aortic arch. Diagnosis was confirmed by positron emission
      tomography and by blood cultures positive for Salmonella species. A complete
      resection of the aortic arch process was performed via left thoracotomy using a
      cryopreserved aortic homograft and normothermic left heart bypass. The left-sided
      cerebral vessels were clamped, and adequacy of collateral left brain flow and
      oxygenation was confirmed by neurophysiologic monitoring. Using this less
      invasive operative strategy, we avoided the risks inherent to deep hypothermic
      circulatory arrest and the use of prosthetic materials.

PMID- 17041696
TI  - Catheterization of the AbioCor implantable replacement heart: evaluation of the
      unique physiology created by the device.
AB  - We performed the 1st catheterization of an AbioCor implantable replacement heart,
      in a patient who had developed high right-sided pump pressures, to determine
      whether the high pressures were caused by graft kinking or obstruction.

PMID- 17041697
TI  - Clinical presentation of persistent 5th aortic arch: 3 new cases.
AB  - We report 3 cases of a persistent 5th aortic arch. This anomaly is usually
      associated with other intracardiac defects. Although all 3 patients were found to
      have similar vascular structures that were best explained by the persistence of
      the 5th aortic arch into postnatal life, the clinical presentations were quite
      different. One patient presented with coarctation of the aorta, the 2nd patient
      with cyanosis, and the 3rd patient with pulmonary overcirculation. The 2nd case
      is unique in that the 5th aortic arch was found to be sensitive to prostaglandin
      E1. Understanding the embryologic derivation and differing presentations of a
      persistent 5th aortic arch aids in diagnosis and management of these patients.

PMID- 17041698
TI  - Successful transcatheter coil occlusion of a right-sided patent ductus arteriosus
      with aberrant left subclavian artery.
AB  - Right aortic arch is a relatively rare congenital anomaly. The combination of a
      right aortic arch, a right patent ductus arteriosus, and an aberrant left
      subclavian artery in a child with an otherwise structurally normal heart is very
      uncommon. We report the successful transcatheter coil occlusion of a right-sided
      patent ductus arteriosus in a child with the above-mentioned anatomy. To our
      knowledge, such a case has not been reported in the English-language medical
      literature to date.

PMID- 17041699
TI  - Chronic pseudoaneurysm and coarctation of the aorta: a rare delayed complication
      of trauma.
AB  - We report an unusual case of pseudoaneurysm and coarctation of the descending
      thoracic aorta after trauma. The coarctation of aorta resulted in hypertension,
      severe left ventricular dysfunction, and symptoms of congestive heart failure.
      Surgical bypass resulted in control of blood pressure and improvement of heart
      failure symptoms. The mechanism of aortic injury leading to the development of
      this rare combination is discussed.

PMID- 17041700
TI  - Endoluminal stenting of mycotic saccular aneurysm at the aortic arch.
AB  - Endovascular grafts have been widely used for the treatment of aneurysms since
      the early 1990s. They are preferred especially for use in patients in whom
      conventional surgical methods carry high risks of death and morbidity. Increasing
      operator experience and technical refinements in endovascular grafting have
      enabled these procedures to be performed even in critical segments of the aorta,
      such as the thoracic and arch levels. In this report, we present the case of a
      patient who was treated successfully with an endovascular graft for a mycotic
      saccular aneurysm located just below the left subclavian artery.

PMID- 17041701
TI  - Nonsurgical management of left main coronary artery aneurysms: report of 2 cases
      and review of the literature.
AB  - Aneurysms of the left main coronary artery are exceedingly rare clinical
      entities, encountered incidentally in approximately 0.1% of patients who undergo
      routine angiography. Thrombosis within the aneurysm can lead to distal
      embolization and myocardial infarction. These lesions can extend into adjacent
      coronary branches and can occur in the presence or absence of obstructive
      coronary disease. Depending on the severity of coexistent coronary stenoses,
      patients with left main coronary artery aneurysms can be effectively managed
      either operatively or medically. We report the cases of 2 patients who were
      treated medically for large left main coronary aneurysms and concomitant right
      coronary artery ectasia.

PMID- 17041702
TI  - Daughter, you broke my heart: accidental thrombosis at a muscular bridge.
AB  - We report the case of a 59-year-old trained runner, who sustained an acute
      myocardial infarction, with residual effort angina, following extreme exertion
      while experiencing severe anxiety. Coronary angiography revealed that this
      patient had a myocardial bridge at the mid-left anterior descending artery, and
      an occlusive clot had developed at the proximal end of the muscular bridge. We
      discuss the possible relationships between the various circumstances of this
      sudden event. We argue that, under exceptional conditions, myocardial bridges can
      lead to myocardial infarction by clot formation.

PMID- 17041703
TI  - Transcatheter treatment of "pulmonary artery hypertension" due to patent ductus
      arteriosus and pulmonary artery stenosis.
AB  - The association between large, left-sided patent ductus arteriosus and severe,
      peripheral, right pulmonary artery stenosis with no other cardiac malformation is
      an unreported condition that might be misdiagnosed as pulmonary hypertension due
      to long-standing ductal shunt. A 57-year-old man with supposed hypertensive
      patent ductus arteriosus underwent confirmatory cardiac catheterization. At
      angiography, a severe pre-hilar right pulmonary artery stenosis (peak pressure
      gradient, 65 mmHg) was found to complicate the hemodynamic picture of a moderate
      to-large patent ductus arteriosus (QP/QS, 1.7:1), by causing pulmonary
      hypertension (mean pressure, 65 mmHg) and left-to-right pulmonary flow imbalance.
      Both lesions were treated in a single procedure of right pulmonary artery
      stenting and patent ductus arteriosus closure, after which the pulmonary artery
      pressure significantly decreased (mean, 35 mmHg). In our opinion, a thorough
      hemodynamic evaluation followed by pulmonary angiography should be mandatory
      before proceeding to patent ductus arteriosus closure in the adult patient who
      has "hypertensive" ductus, in whom possible associated malformations can be
      missed due to a poor echocardiographic window.

PMID- 17041705
TI  - Giant left atrium with rheumatic mitral stenosis.
AB  - A chest radiograph of a 38-year-old woman, who was diagnosed with rheumatic
      mitral stenosis, revealed cardiac enlargement due to a giant left atrium that was
      distorting the cardiac structures. The patient's cardiothoracic ratio was
      approximately 0.90. A giant left atrium can readily be delineated by
      echocardiography. Optimal timing of surgery is important in cases of mitral
      stenosis, because delaying mitral valve replacement can lead to fatal outcomes.
      To our knowledge, the left atrial diameter of 18.7 cm that we found in our
      patient is the largest reported to date.

PMID- 17041704
TI  - Arrhythmogenic right ventricular dysplasia: initial presentation in a middle-aged
      woman.
AB  - Arrhythmogenic right ventricular dysplasia is a rare disorder that is familial in
      30% to 50% of cases. It is characterized by structural and functional
      abnormalities of the right ventricle and a propensity for ventricular arrhythmias
      and sudden death. We report the case of a 59-year-old woman who had idiopathic,
      severe, right-sided heart failure and nonsustained ventricular tachycardia. She
      was diagnosed with arrhythmogenic right ventricular dysplasia by means of cardiac
      magnetic resonance imaging. We discuss the clinical features, diagnostic
      criteria, and role of cardiac magnetic resonance imaging in the diagnosis of
      arrhythmogenic right ventricular dysplasia.

PMID- 17041706
TI  - Penetrating trauma to the mitral valve and ventricular septum.
AB  - Penetrating cardiac trauma is typically life-threatening and often requires
      urgent surgical intervention. Penetrating injury can cause damage in more than 1
      cardiac structure that may be difficult to identify at the initial urgent
      operation. We describe the case of a young man in whom a perimembranous
      ventricular septal defect and perforation of the anterior leaflet of the mitral
      valve were caused by a screwdriver wound.

PMID- 17041707
TI  - Symptomatic bradycardia due to total occlusion of left circumflex artery without
      electrocardiographic evidence of myocardial infarction at initial presentation.
AB  - We present the case of a 72-year-old man who was admitted due to low blood
      pressure and acute-onset dizziness with sinus bradyarrhythmia on
      electrocardiography. He had no obvious anginal symptoms, and there was no marked
      evidence of myocardial infarction. He was ultimately diagnosed with coronary
      artery disease with total occlusion of the left circumflex coronary artery, and
      he underwent successful coronary angioplasty after primary conduction disorders
      were ruled out.

PMID- 17041708
TI  - Left ventricular outflow tract obstruction after bioprosthetic mitral valve
      replacement with posterior mitral leaflet preservation.
AB  - We present a case of transient left ventricular outflow tract obstruction after
      mitral valve replacement with a high-profile bioprosthesis; only the posterior
      native mitral valve leaflet was preserved. A 76-year-old woman was admitted to
      our institution with pulmonary edema. Two weeks earlier, she had undergone mitral
      valve replacement at our hospital due to severe mitral stenosis and 2+ mitral
      regurgitation complicated by cardiac failure and atrial fibrillation. The patient
      was taking digoxin, furosemide, and warfarin at the time of readmission.
      Echocardiography showed a narrowed left ventricular outflow tract. Doppler
      echocardiography revealed a peak 64-mmHg gradient between the septum and the
      strut of the bioprosthesis. The patient was successfully treated medically. This
      case indicates that the risk of left ventricular outflow tract obstruction after
      bioprosthetic mitral valve replacement is not always eliminated by removal of the
      anterior mitral valve leaflet when the posterior mitral leaflet is preserved.

PMID- 17041709
TI  - Use of a nasal speculum for chest-drain insertion: a simple technique.
AB  - Tube thoracostomy is a very commonly performed procedure in cardiothoracic
      surgery. Insertion of a chest drain requires expertise to minimize complications.
      We describe a simple technique of using a nasal speculum to perform this
      procedure.

PMID- 17041710
TI  - Nontraumatic pericardiophrenic defect with tamponade.

PMID- 17041711
TI  - An unusual course of the ramus intermedius: shown by multislice computed
      tomographic coronary angiography.

PMID- 17041712
TI  - Apical hypertrophic cardiomyopathy: diagnosed by cardiac magnetic resonance
      imaging.

PMID- 17041713
TI  - A closed interatrial septal aneurysm mimicking a tumor in the left atrium.

PMID- 17041714
TI  - Chimpanzee heart was not rejected by human recipient.

PMID- 17041715
TI  - Use of a recirculator device for pericardial cold saline irrigation in cardiac
      surgery.

PMID- 17041716
TI  - Pharmacologic targets and prototype therapeutics in the kallikrein-kinin system:
      bradykinin receptor agonists or antagonists.
AB  - The kallikrein-kinin system (KKS) is a complex system produced in various organs.
      This system includes kininogen (precursor for kinin), kallikreins, and
      pharmacologically active bradykinin (BK), which is considered to be
      proinflammatory and/or cardioprotective. It is a proinflammatory polypeptide that
      is involved in many pathological conditions and can cause pain, inflammation,
      increased vascular permeability, vasodilation, contraction of various smooth
      muscles, as well as cell proliferation. On the other hand, it has been shown that
      BK has cardioprotective effects, as all components of KKS are located in the
      cardiac muscles. Numerous observations have indicated that decreased activity of
      this system may lead to cardiovascular diseases, such as hypertension, cardiac
      failure, and myocardial infarction. BK acts on two receptors, B1 and B2, which
      are linked physiologically through their natural stimuli and their common
      participation in a variety of inflammatory responses. Recently, numerous BK
      antagonists have been developed in order to treat several diseases that are due
      to excessive BK formation. Although BK has many beneficial effects, it has been
      recognized to have some undesirable effects that can be reversed with BK
      antagonists. In addition, products of this system have multiple interactions with
      other important metabolic pathways, such as the renin-angiotensin system.

PMID- 17041717
TI  - Infusion of autologous retrodifferentiated stem cells into patients with beta
      thalassemia.
AB  - Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin
      chain of the adult hemoglobin gene. This results in excess accumulation of
      unpaired alpha-chain gene products leading to reduced red blood cell life span
      and the development of severe anemia. Current treatment of this disease involves
      regular blood transfusion and adjunct chelation therapy to lower blood
      transfusion-induced iron overload. Fetal hemoglobin switching agents have been
      proposed to treat genetic blood disorders, such as sickle cell anemia and beta
      thalassemia, in an effort to compensate for the dysfunctional form of the beta
      globin chain in adult hemoglobin. The rationale behind this approach is to pair
      the excess normal alpha-globin chain with the alternative fetal gamma-chain to
      promote red blood cell survival and ameliorate the anemia. Reprogramming of
      differentiation in intact, mature, adult white blood cells in response to
      inclusion of monoclonal antibody CR3/43 has been described. This form of
      retrograde development has been termed "retrodifferentiation", with the ability
      to re-express a variety of stem cell markers in a heterogeneous population of
      white blood cells. This form of reprogramming, or reontogeny, to a more
      pluripotent stem cell state ought to recapitulate early hematopoiesis and
      facilitate expression of a fetal and/or adult program of hemoglobin synthesis or
      regeneration on infusion and subsequent redifferentiation. Herein, the outcome of
      infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with
      beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC
      subjected to hematopoietic-conducive conditions into patients with beta
      thalassemia reduced mean blood transfusion requirement, increased mean fetal
      hemoglobin synthesis, and significantly lowered mean serum ferritin. This was
      always accompanied by an increase in mean corpuscular volume (MCV), mean
      corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration
      (MCHC) in such patients. No adverse side effects in response to the infusion of
      autologous RSC were noted. This novel clinical procedure may profoundly modify
      the devastating course of many genetic disorders in an autologous setting, thus
      paving the way to harnessing pluripotency from differentiated cells to regenerate
      transiently an otherwise genetically degenerate tissue such as thalassemic blood.

PMID- 17041718
TI  - xSyndecan-4 regulates gastrulation and neural tube closure in Xenopus embryos.

PMID- 17041719
TI  - The Israeli Rett Syndrome Center. Evaluation and transdisciplinary play-based
      assessment.
AB  - Rett syndrome (RS) is a neuro-developmental syndrome of genetic origin, which
      mainly affects women. Individuals diagnosed with RS exhibit a variety of
      functional difficulties, which impair their quality of life. The variety of
      impairments and the differences between each child makes it necessary to
      administer skilled treatment, individually tailored to each client. Since the
      foundation of proper treatment is based on a structured, well administered,
      insightful assessment, the individual with RS with her complex array of
      difficulties should benefit from such a procedure. This notion has led to the
      establishment of the Israel Rett Syndrome Center. The center includes a medical
      branch located at the Safra Shildren's Medical Center at Tel Hashomer and an
      education/rehabilitation team, who performs assessments in special education
      facilities and residential settings throughout Israel. The assessment team works
      by means of arena assessment according to the concept of play-based assessment.
      This article presents the working model used by the education/rehabilitation team
      at the Israeli Rett Syndrome Center. The principles and working characteristics
      of the Israel Rett Syndrome Center team are suggested here as a potential model
      for establishing additional teams, presenting similar evaluation services for
      other individuals with RS as well as for analogous populations.

PMID- 17041720
TI  - Physical therapy intervention for individuals with Rett syndrome.
AB  - Individuals with Rett syndrome (RS) present a vast array of orthopedic and
      neurological difficulties. Typical problems, which may need to be addressed, when
      treating this population are functional limitations, low cardiovascular capacity,
      hypotonia, ataxia, apraxia, loss of transitional movements, spasticity, scoliosis
      and/or kyphosis, loss of ambulation, loss of hand function, foot deformities, and
      spatial disorientation. Coping with such difficulties and overcoming the
      associated limitations carry a wearisome task for the individual with Rett as
      well as for her family. An informed and intensely applied physical therapy regime
      can help the child and the family cope and even overcome the above-mentioned
      limitations. The present article presents some insights regarding the
      intervention with individuals with RS, an overview of typical neuromuscular
      problems associated with RS, and appropriate suggestions pertaining to clinical
      intervention that have been found to contribute to this population's well-being.
      The information presented is mainly based on the clinical knowledge of the
      authors.

PMID- 17041721
TI  - Effects of caloric restriction and exercise training on skeletal muscle
      histochemistry in aging Fischer 344 rats.
AB  - The purpose of this study was to determine the effects of calorie restriction and
      exercise on hindlimb histochemistry and fiber type in Fischer 344 rats as they
      advanced from adulthood through senescence. At 10 months of age, animals were
      divided into sedentary fed ad libitum, exercise (18 m/min, 8% grade, 20 min/day,
      5 days/week) fed ad libitum, and calorie restricted by alternate days of feeding.
      Succinic dehydrogenase, myosin adenosine triphosphatase (mATPase at pH 9.4),
      nicotine adenonine dinucleotide reductase, and Periodic Acid Shiff histochemical
      stains were performed on plantaris and soleus muscles. The results indicated that
      aging resulted in a progressive decline in plantaris Type I muscle fiber in
      sedentary animals, while exercise resulted in maintenance of these fibers. The
      percent of plantaris Type II fibers increased between 10 and 24 months of age.
      Exercise also resulted in a small, but significant, increase in the percentage of
      plantaris Type IIa fibers at 24 months of age. The soleus fiber distribution for
      Type I fibers was unaffected by increasing age in all groups of animals. The
      implications of these results suggest the implementation of exercise as a
      lifestyle modification as early as possible.

PMID- 17041722
TI  - [Biological effects of toosendanin, an active ingredient of herbal vermifuge in
      Chinese traditional medicine].
AB  - The fact that the fruit and bark of plant belonging to family Melia could be used
      as digestive tract-parasiticide and agricultural insecticide was recorded about
      two thousand years ago in ancient China. Toosendanin (TSN, C30H38O11, FW=574), a
      triterpenoid derivative, was extracted from the bark of Melia toosendan Sieb. et
      Zucc. by Chinese scientists in 1950os and used as an ascarifuge in China instead
      of imported sendanin. Studies have demonstrated that TSN possesses special
      biological actions as well as considerable various values in scientific research,
      clinic medicine and agriculture. The first is that by interfering with
      neurotransmitter release by causing an initial facilitation, TSN eventually
      blocks synaptic transmission at both the neuromuscular junction and central
      synapses. The action might result from TSN-induced Ca(2+)-sensitivity change and
      final elimination of transmitter release machinery. The second is that despite
      sharing many similar actions with botulinum neurotoxin (BoNT) on blocking
      neuromuscular transmission, TSN has a markedly antibotulismic action in vivo and
      in vitro: TSN-treatment saves the botulism mice or monkeys from death; TSN
      incubation in vitro or TSN-injection in vivo endows neuromuscular junction with a
      high tolerance to BoNT. Studies suggest that the antibotulismic action is
      achieved by preventing BoNT from approaching its enzymatic substrate, SNARE
      protein. The third, in recent years, it is also observed that TSN can induce
      differentiation and apoptosis in several cell lines, and suppress proliferation
      of various human cancer cells. The TSN-induced differentiation is Ca(2+)
      dependent and the mitochondria-dependent apoptosis pathway is involved in the TSN
      induced apoptosis. The fourth is that TSN inhibits various K(+) channels and
      selectively facilitates Ca(2+) current through L-type Ca(2+) channels and hence
      elevates [Ca(2+)](i). The TSN-induced [Ca(2+)](i) increase and overload could be
      responsible for the TSN-induced biphasic effect on neurotransmitter release, cell
      differentiation, apoptosis as well as the cytotoxicity of TSN.

PMID- 17041723
TI  - Postsynaptic calcium pathway contributes to synaptic plasticity between retinal
      cones and luminosity-type horizontal cells.
AB  - It was previously found that the efficacy of synaptic transmission between
      retinal cone systems and luminosity-type horizontal cells (LHCs) was activity
      dependent. Repetitive activation of red-cone pathway increased the LHCos
      hyperpolarizing response to red light, and the response enhancement was
      reversible. In this study, intracellular recording and pharmacological method
      were applied to investigate the mechanism(s) underlying red-flickering-induced
      response enhancement. Lowering intracellular Ca(2+) in the LHC by intracellular
      injection of Ca(2+) chelator EGTA prevented the development of red-flickering
      induced response enhancement, which implicates the importance of postsynaptic
      calcium signal. The response enhancement could also be eliminated by a potent
      antagonist of Ca(2+)-permeable AMPA receptor (CP-AMPAR), which suggests the
      possibility that Ca(2+) influx via glutamate-gated calcium channels is related to
      the changes of [Ca(2+)](i). Furthermore, the administration of ryanodine or
      caffeine also attenuated the phenomenon, which gives evidence that the local
      calcium signal caused by intracellular calcium-induced calcium release (CICR) may
      be involved. Taken together, our data implicate that postsynaptic CICR and CP
      AMPAR are related to the activity-dependent response enhancement.

PMID- 17041724
TI  - Forced running enhances neurogenesis in the hippocampal dentate gyrus of adult
      rats and improves learning ability.
AB  - To investigate the effect of forced running in motor-driven wheel on neurogenesis
      in the hippocampal dentate gyrus (DG) of adult rats, 5-bromo-2-deoxyuridine
      (BrdU), a thymidine analog was applied to mark cell proliferation. Neuroepthelial
      stem cell protein (nestin) expression was used to identify neural stem/precursor
      cells. The BrdU- and nestin-positive cells were examined by immunohistochemical
      technique. The ability of learning was evaluated by Y-maze test to explore the
      functional role of the newborn cells in the DG after forced running. It was found
      that the number of BrdU- and nestin-positive cells in the DG in running groups
      was significantly increased compared to that in the control group (P<0.05). The
      effect of forced running on neurogenesis was intensity-dependent. In addition, an
      improvement of learning ability in Y-maze test was observed after forced running.
      These findings suggest that forced running in motor-driven wheel could enhance
      neurogenesis in the hippocampal DG of adult rats and improve learning ability.

PMID- 17041725
TI  - [Overexpression of alpha-synuclein in SH-SY5Y cells partially protected against
      oxidative stress induced by rotenone].
AB  - Both genetic and environmental factors are involved in the pathogenesis of
      Parkinsonos disease (PD). Epidemiological studies showed that environmental
      factors shared with the common mechanisms of resulting in alpha-synuclein
      aggregation by inhibiting complex I of mitochondria and leading to oxidative
      stress. To investigate the relationship between alpha-synuclein and oxidative
      stress, we used human dopaminergic SH-SY5Y cells transfected with alpha-synuclein
      enhanced green fluorescent protein (EGFP). alpha-synuclein gene expression was
      determined by immunocytochemistry and real-time quantitative PCR. Both SH-SY5Y
      and alpha-synuclein overexpressed SH-SY5Y (SH-SY5Y/Syn) cells were treated with
      various concentrations of rotenone for different time. Cell viability and
      oxidative stress were detected by MTT assay and DCF assay. Superoxide dismutase
      (SOD) activity was assessed with xanthine peroxidase method. Cell apoptosis was
      detected with flow cytometry. Results showed that alpha-synuclein gene was
      constantly overexpressed in SH-SY5Y/Syn cells. After treatment with rotenone,
      both cell viability and complex I activity in these cells were reduced in a
      concentration-dependent manner. Oxidative stress was also found in these cells.
      Compared with SH-SY5Y cells, SOD activity in SH-SY5Y/Syn cells was increased
      distinctly (P<0.05) and alpha-synuclein significantly attenuated rotenone-induced
      cell apoptosis. These results suggest that the alpha-synuclein overexpression in
      SH-SY5Y cells has a tendency to partially resist oxidative stress induced by
      rotenone and this response may assist cell survival.

PMID- 17041726
TI  - [Expression of caveolin-1 protein in the rat brain and its role in the
      discrimination learning].
AB  - Caveolin-1 (Cav-1) is a marker protein for caveolae, and acts as scaffolding
      protein to regulate the activities of signaling molecules. Previous studies
      indicate that Cav-1 mainly locates at the base of axonal and dendritic terminals
      of mouse primary hippocampal neurons and plays an active role in the regulation
      of injury-induced synaptic and terminal remodeling in central nervous system. The
      aim of this study was to identify the expression profile of Cav-1 protein in the
      brains of rats at different ages and to investigate the role of Cav-1 in Y-maze
      bright-dark discrimination learning (BDL). Firstly, the expressions of Cav-1 in
      the brains of young (1-month), adult (3-month) and aged (22-month) rats were
      observed by Western blot. Higher expression in the hippocampus and lower
      expression in the cortex were shown in the adult rats. It was also found that the
      score of BDL was related with the expression level of Cav-1. Secondly, using open
      field test for spontaneous locomotor activities (SLA) and BDL, the role of Cav-1
      in the learning and memory was observed. Compared with that in the control adult
      group, the Cav-1 protein expression in the hippocampus and prefrontal cortex of Y
      maze trained adult rats significantly increased, while no marked changes in the
      cerebellum. These results suggest that Cav-1 protein is involved in BDL and plays
      an important role in the plasticity of central nervous system.

PMID- 17041727
TI  - Forskolin and 8-cyclopentyltheophylline synergistically facilitate the neuronal
      activity in the CA2 area of rat hippocampus via cAMP and non-cAMP cascades.
AB  - High level of adenosine A1 receptor-like immunoreactivity has been found in the
      CA2/CA3a region of adult rat hippocampus, but its roles in the neuronal activity
      or signal propagation in hippocampus and its intracellular cascade remain to be
      studied. In this study, we examined the relation between adenosine-3',5'-cyclic
      monophosphate (cAMP) cascade and suppression of synaptic transmission by
      endogenous adenosine through adenosine A1 receptor in the CA2 area. In transverse
      hippocampal slice, maximal electrical stimulation of the hilus region (0.6 mA)
      only evoked small population spikes (PSs) in the CA2 area (0.5 mV). In the
      presence of forskolin (20 micromol/L), a direct adenylate cyclase activator, PSs
      in CA2 were increased to 1.1 mV. When 8-cyclopentyltheophylline (8CPT, 2
      micromol/L), an adenosine A1 receptor antagonist, was added in the presence of 20
      micromol/L forskolin, PSs with an average amplitude of 4.7 mV were recorded in
      the CA2 area, much higher than the sum of the amplitude of PSs in the presence of
      forskolin and 8CPT alone. To test whether this synergistic potentiation results
      from the additive activation of cAMP cascade, the cAMP content in hippocampal
      slices was measured with enzyme immunoassay (EIA). Results showed that 8CPT did
      not increase the cAMP content in CA2 with or without forskolin. Co-application of
      forskolin and Ro 20-1724, a cAMP-specific phosphodiesterase-IV inhibitor, only
      increased PSs in CA2 to 1.3 mV but increased cAMP content by 4.4 times. On the
      other hand, co-application of 8CPT and 1, 9-dideoxyforskolin, a forskolin analog
      which has no effect on adenylate cyclase, did not mimic the synergistic effect of
      8CPT and forskolin on PSs in CA2. These results indicate that up-regulation of
      adenylate cyclase activity and inhibition of adenosine A1 receptor activity
      synergistically facilitate the neuronal activity in the CA2 area and the effect
      of adenosine A1 receptor antagonist is via non-cAMP cascade. These data also
      suggest that acting on adenosine A1 receptors, endogenous and extragenous
      adenosine/adenosine A1 agonist(s) inhibit neuronal activity through different
      pathways.

PMID- 17041728
TI  - [Changes of NMDA receptor expression in rat hippocampal formation after
      establishment of spatial memory by different training modes].
AB  - There is no unambiguous report so far on whether short reinforcing training could
      establish stable spatial long-term memory and how the NMDA/NR1 expression in the
      hippocampal formation changes after establishment of short- and long-term memory.
      In the present study, three spatial memory training modes of Morris water maze
      were used: spatial long-term memory training mode (LT group), spatial short-term
      memory training mode (ST group) and short reinforcing training mode (SRT group).
      The characteristics of those memories established by different training modes
      were compared. The immunofluorescence histochemical staining technique was used
      to observe the changes of NMDA/NR1 expression in the hippocampal formation in the
      three groups. The results showed that, during Morris water maze training, no
      significant difference was found in the mean latency and the strategies to the
      target between the LT and SRT groups. The examination of the memories following
      different trainings indicated that the mean latency and the strategies to the
      target as well as the times crossing the target in LT group were not
      significantly different from those in SRT group, except that the mean time
      remaining in the platform quadrant in LT group was significantly longer than that
      in SRT group. In addition, no significant difference in the intensity of NMDA/NR1
      immunoreactivity in CA1, CA3 and dentate gyrus of the hippocampal formation was
      observed between the control and ST groups or between LT and SRT groups. However,
      the intensity of NMDA/NR1 immunoreactivity in CA1 area and dentate gyrus in both
      LT and SRT groups was significantly increased as compared with that in ST or the
      control groups. These results suggest that the short reinforcing training mode
      can establish long-term spatial memory, which is almost the same as that
      established by the long-term training mode, and that the increase of NMDA/NR1
      expression in CA1 area and dentate gyrus of the hippocampal formation may be one
      of the mechanisms of spatial long-term memory formation.

PMID- 17041729
TI  - [Effects of sodium salicylate on the expressions of gamma-aminobutyricacid and
      glutamate and auditory response properties of the inferior colliculus neurons].
AB  - The effects of sodium salicylate (NaSA) on the expressions of gamma
      aminobutyricacid (GABA) and glutamate (Glu), and auditory response properties of
      the inferior colliculus neurons in mice were studied. Thirty-six Kunming mice
      were divided into three groups: control group (saline injection); NaSA group
      (NaSA 450 mg/kg, i.p., each day for 15 d); NaSA + lidocaine group (NaSA 450 mg/kg
      + lidocaine 10 mg/kg, i.p., each day for 15 d). The expressions of GABA and Glu
      were examined with immunohistochemical method. The intensity-rate function,
      intensity-latency function and frequency-tuning curve were determined with
      extracellular electrophysiological recording. Results are as follows: (1) The
      expression of GABA in the NaSA and NaSA + lidocaine groups decreased remarkably
      compared with that in the control group; there was no noticeable difference
      between the NaSA and NaSA + lidocaine groups. The expression of Glu in the NaSA
      group increased significantly compared with that in the control and NaSA +
      lidocaine groups. No difference in the expression of Glu was found between the
      control and NaSA + lidocaine groups. (2) In NaSA group, the intensity-rate
      function displayed a non-monotonic pattern, rising at low intensity and
      descending at high intensity; the tip of frequency-tuning curves became broad
      after administration of NaSA. (3) The changes in intensity-rate function and
      intensity-latency function were not evident and the tips of the frequency-tuning
      curves sharpened in the NaSA + lidocaine group. These results suggest that
      administration of NaSA increases the expression of Glu-positive neurons and
      reduces that of GABA-positive neurons in the inferior colliculus. NaSA changes
      the auditory response properties of the inferior colliculus and lidocaine can
      reverse these changes.

PMID- 17041730
TI  - [Effects of chloride channel blockers on excitatory junction potentials in smooth
      muscle cells of cochlear spiral modiolar artery in guinea pigs].
AB  - Chloride channels have been identified in vascular smooth muscle cells (SMCs). It
      has been shown that these channels are involved in myogenic tone regulation and
      neuromuscular transmission in various vascular beds. However, whether the
      chloride channels are responsible for the formation of excitatory junction
      potentials (EJPs) of SMCs in the spiral modiolar artery (SMA) remains
      unelucidated. In the present study, the effects of chloride channel blockers
      (niflumic acid, NFA; indanyloxyacetic acid 94, IAA-94; disodium 4, 4'
      diisothiocyanatostilbene-2, 2'-disulfonate, DIDS) on EJP were explored in guinea
      pigs, using intracellular recording techniques on acutely isolated SMA. It was
      found that EJP was evoked in the majority of the SMCs (75%, n=49) with an
      adequate electronic stimulation. The amplitude of the EJP was partially blocked
      (30% approximately 80%) by combined application of alpha(1) receptor antagonist
      (prazosin) and alpha(2) receptor antagonist (idazoxan) at concentration of up to
      1 micromol/L, and P(2x) receptor antagonist (PPADS, 10 approximately 100
      micromol/L). NFA (100 micromol/L) could further inhibit the residual EJP in the
      presence of alpha(1), alpha(2)-adrenergic and P(2x) receptor antagonists. IAA-94
      or DIDS not only inhibited the amplitude but also shortened the duration of EJP.
      Decrease of extracellular chloride concentration from 135.6 mmol/L to 60 mmol/L
      would enhance EJP. Moreover, IAA-94 (100 micromol/L) and DIDS (200 mumol/L) could
      reverse the enhancement of EJP by low extracellular Cl(-). NFA (100 micromol/L)
      could also block the residual depolarizations evoked by norepinephrine (NE, 1
      approximately 50 micromol/L). Based on these results, it is inferred that NE
      could activate a novel adrenoceptor to open the chloride channel on the membrane
      of the SMCs, leading to a transmembrane Cl(-) current. This current is involved,
      at least partially, in the formation of EJP.

PMID- 17041731
TI  - [Hypoxic preconditioning induces endoplasmic reticulum stress-related
      cardioprotection mediated by p38 mitogen-activated protein kinase].
AB  - Calreticulin (CRT), an important Ca(2+)-binding molecular chaperone in the
      endoplasmic reticulum (ER), and caspase-12, a pivotal molecule mediating ER
      initiated apoptosis, are involved in the ER stress (ERS). Using primary cultured
      neonatal cardiomyocytes, CRT and caspase-12 expression and activation during
      hypoxic preconditioning (HPC) and hypoxia/reoxygenation (H/R) were studied to
      explore the role of ERS in cardioprotection by HPC. And by using SB203580 and
      SP600125 [the specific inhibitors of p38 mitogen-activated protein kinase (MAPK)
      and c-Jun N-terminal kinase (JNK)] separately, the role of p38 MAPK in HPC
      induced ERS was also detected. Neonatal cardiomyocytes were prepared from Sprague
      Dawley rats aged 24 h, and cultured in DMEM medium containing 10% fetal bovine
      serum, and then randomly divided into six groups as follows: H/R, HPC+H/R,
      SB203580+HPC+H/R, SP600125+HPC+H/R, HPC and control groups. H/R was produced by 2
      hour hypoxia/14-hour reoxygenation, and HPC by 20-minute hypoxia/24-hour
      reoxygenation. Morphological studies, estimation of lactate dehydrogenase (LDH)
      leakage and flow cytometry were employed to assess cell apoptosis and necrosis.
      CRT and caspase-12 expression and activation, levels of phospho-p38 MAPK and
      phospho-JNK were detected by Western blot. All experiments were repeated at least
      four separate times. The results obtained are as follows: (1) HPC relieved the
      cell injury caused by H/R. Compared with that in H/R group, cellso survival rate
      in HPC+H/R group increased by 6.4%, and the apoptosis rate and LDH leakage in the
      cell culture medium decreased by 6.6% and 70.0%, respectively. (2) H/R induced
      caspase-12 activation (33.2-fold increase in comparison with control) and CRT
      expression (8.1-fold increase in comparison with control). HPC itself resulted in
      mild CRT up-regulation (2.6-fold increase in comparison with control), but the
      extent of up-regulation was lower than that induced by H/R. HPC before H/R was
      found to relieve the over-expression of CRT induced by H/R (72.4% decrease), and
      to inhibit the activation of caspase-12 (59.6% decrease). (3) The protection of
      HPC and HPC-induced up-expression of CRT and inhibition of caspase-12 activation
      were almost eliminated when the inhibitor of p38 MAPK, not of JNK, was present
      before HPC. These results suggest that HPC protects the neonatal cardiomyocytes
      from severe ERS-induced apoptosis during sustained H/R through pre-invoking
      proper ERS response. Mild up-expression of CRT and inhibition of caspase-12
      activation induced by HPC, which are important protection factors, are mediated
      by p38 MAPK, not by JNK.

PMID- 17041732
TI  - [Calcium-dependent chloride channels in plasma membrane of oocytes from toad,
      Bufo bufo gargarizans].
AB  - In this paper, membrane current properties of the fully-grown oocytes from toad,
      Bufo bufo gargarizans, were studied by using two-microelectrode voltage clamp
      technique. Axion of adult female toad was destroyed, and then ovarian lobes
      containing oocytes in stage I to VI were removed and incubated in Ca(2+)-free
      ND96 solution with collagenase (1.5 mg/ml) for 1 h. Subsequently, the oocytes
      were washed in Ca(2+)-free ND96 solution for 10 min to completely remove the
      follicular layer. For the experiments only the oocytes in stage V and VI were
      selected and used during 1 to 5 d. The membrane was depolarized from a holding
      potential of -80 mV to +60 mV in 10 mV step. It was found that a sustained
      outward current was elicited by depolarization. Potassium channel blockers
      (tetraethylammonium chloride, TEA, 10 mmol/L and 4-aminopyridine, 4-AP, 10
      mmol/L) reduced the outward current to (23.4+/-0.72)% of the maximum. However,
      further addition of chloride channel blocker (5-nitro-2, 3-phenypropylamino
      benzoate, NPPB, 30 micromol/L) could almost completely block the outward current
      to (2.1+/-0.08)% of the maximum. In the presence of TEA and 4-AP, removal of
      extracellular Ca(2+) or adding verapamil (40 micromol/L), could also reduce the
      outward current to (2.2+/-0.04) % and (3.1+/-0.15) % of the maximum,
      respectively. It is concluded that calcium-dependent chloride channels exist in
      plasma membrane of Bufo bufo gargarizans oocytes, besides potassium channels.

PMID- 17041733
TI  - [Electrophysiological study on rat conduit pulmonary artery smooth muscle cells
      under normoxia and acute hypoxia].
AB  - The present study was designed to investigate the electrophysiological
      characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and
      the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the
      conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were
      divided into acute hypoxia preconditioned group and normoxia group. Hypoxia
      solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min
      before cell perfusion. Potassium currents were compared between these two groups
      using whole-cell patch clamp technique. The total outward current of PASMCs was
      measured under normoxia condition when iBTX [specific blocking agent of large
      conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent
      of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath
      solution. PASMCs were classified into three types according to their size, shape
      and electrophysiological characteristics. Type I cells are the smallest with
      spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show
      the biggest size with banana-like appearance. Type III cells have the similar
      size with type I, and present intermediary shape between type I and type II. iBTX
      had little effect on the total outward current in type I cells, while 4-AP almost
      completely blocked it. Most of the total outward current in type II cells was
      inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells,
      the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia
      reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/
      33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for
      type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III
      (P<0.01), and raised the resting membrane potentials (E(m)) in all these three
      types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV
      to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for
      type I, II, III cells, respectively. These results suggest that acute hypoxia
      suppresses the potassium current and improves the E(m) in PASMCs. These effects
      may be involved in the modulation of constriction/relaxation of conduit artery
      under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these
      three types of PASMCs might account for their different constriction/relaxation
      response to acute hypoxia.

PMID- 17041734
TI  - Carbon monoxide inhalation protects lung from lipopolysaccharide-induced injury
      in rat.
AB  - Carbon monoxide (CO), a metabolite of heme catalysis by heme oxygenase (HO), has
      been proposed to have anti-oxidative, anti-inflammatory and anti-apoptotic
      functions. Lipopolysaccharide (LPS)-induced lung injury (LI) is characterized by
      oxidative stress, inflammatory reaction and excessive pulmonary cell apoptosis.
      So we supposed that CO might have protection against LI. LI in rats was induced
      by intravenous injection of LPS (5 mg/kg). To observe the effect of CO
      inhalation, LI rats were exposed to 2.5 x 10(-4) (V/V) CO for 3 h. CO-induced
      changes of lung oxidative stress parameters, inflammatory cytokines, cell
      apoptosis, HO-1 expression and histology were examined. Results revealed that
      expressions of the tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL
      6), activities of maleic dialdehyde (MDA) and myeloperoxidase (MPO), and cell
      apoptosis in LPS injection + CO inhalation group were (0.91+/-0.25) pg/mg
      protein, (0.64+/-0.05) pg/mg protein, (1.02+/-0.23) nmol/mg protein, (7.18+/
      1.62) U/mg protein and (1.60+/-0.34)%, respectively, significantly lower than the
      corresponding values in LI group [(1.48+/-0.23) pg/mg protein, (1.16+/-0.26)
      pg/mg protein, (1.27+/-0.33) nmol/mg protein, (8.16+/-1.49) U/mg protein and
      (3.18+/-0.51) %, P<0.05]. Moreover, CO inhalation obviously increased the
      expressions of HO-1 and interlukin-10 (IL-10) and activity of superoxide
      dismutase (SOD) [(5.43+/-0.92), (0.26+/-0.07) pg/mg protein and (60.09+/-10.21)
      U/mg protein in LPS injection + CO inhalation group vs (3.08+/-0.82), (0.15+/
      0.03) pg/mg protein and (50.98+/-6.88) U/mg protein in LI group, P<0.05]. LI was
      attenuated by CO inhalation. Our study demonstrates that inhalation of low
      concentration of CO protects lung against LPS-induced injury via anti-oxidant,
      anti-inflammation, anti-apoptosis and up-regulation of HO-1 expression.

PMID- 17041735
TI  - [Formation of platelets from cord blood CD34+ cells-derived megakaryocytes
      induced by S-nitrosoglutathione].
AB  - To investigate the effect of S-nitrosoglutathione (GSNO), a nitric oxide donor,
      on platelet production from megakaryocytes differentiated from cord blood CD34(+)
      cells in vitro, the CD34 (+) cells from eight fresh umbilical cord blood samples
      by a high-gradient magnetic cell sorting (MACS) system were cultured in serum
      free medium for 14 d with thrombopoietin (TPO) 50 ng/ml, IL-3 10 ng/ml, stem cell
      factor (SCF) 50 ng/ml and rHuGM-CSF 20 ng/ml. Then, CD61 (+) cells were purified
      by MACS system from these CD34 (+) cells, and were cultured in serum-free medium
      supplemented with TPO 50 ng/ml, IL-3 10 ng/ml and SCF 50 ng/ml in the presence
      (treatment group) and absence (control group) of GSNO for 30 min or 2 h. Platelet
      sized particles were counted by flow cytometry; megakaryocyte structure was
      detected by scanning electron microscope. Aggregation of the thrombin-induced
      platelet particle was observed under inversion microscope. cGMP was assessed by
      commercial ELISA kit. The results showed that, compared with the control group,
      the number of platelet-sized particles significantly increased (P<0.05) in the
      treatment group, in which megakaryocytes presented significant pseudopod
      formation and extensive membrane blebbing. The platelet particle aggregation
      could be observed under microscope after thrombin induction. cGMP activity was
      significantly increased after treatment with GSNO (P<0.05). These results propose
      that GSNO can facilitate platelet production from megakaryocyte, and it may be
      partly through cGMP pathway.

PMID- 17041736
TI  - [Effect of 4 degrees C pretreatment on the membrane current and cell polarity in
      human neutrophils].
AB  - To investigate the role of ion channels in the coupling responses of neutrophils
      to extracellular stimulus, it is necessary to study the membrane ion channel
      activities using patch-clamp technique. However, little has been known about the
      ion channel activities in neutrophils due to the difficulties in forming giga
      seal with pipettes because of small diameter of neutrophils and the easily
      developed polarization. Some studies indicated that favorable results could be
      achieved through pretreatment at low temperature before electrophysiological
      recordings. But it remains unclear whether the pretreatment affects the membrane
      current and why the seal rate increases after low temperature pretreatment. The
      purpose of this study was to investigate the effects of 4 degrees C pretreatment
      on the membrane current and cell polarity in human neutrophils. In the
      experiments, human neutrophils were isolated from fresh peripheral blood of
      healthy volunteers and divided into two groups (room temperature group and 4
      degrees C pretreatment group). Voltage-dependent K(+) (Kv) currents were recorded
      in whole-cell voltage-clamp mode and large-conductance Ca(2+)-activated K(+)
      (BK(Ca)) currents were recorded using inside-out patches. The results showed that
      4 degrees C pretreatment significantly inhibited cell polarity (P<0.05), and it
      took more time for neutrophils to form a polarity-cycle [(534+/-32) s, n=20]
      compared with those at room temperature [(257+/-24) s, n=20]. Meanwhile, seal
      rate significantly increased in 4 degrees C pretreatment group (64%) compared
      with that in the room temperature group (27.5%). The seal rate and cell polarity
      rate during 0 approximately 1 min after 4 degrees C pretreatment were
      significantly different from those at room temperature, while no significant
      difference was found during 9 approximately 10 min between the two groups. Our
      results suggest that 4 degrees C pretreatment can inhibit cell polarity and
      increase seal rate, but has no effects on membrane currents. It is also suggested
      that 0 approximately 1 min after 4 degrees C pretreatment is a more suitable time
      for electrophysiological recording in neutrophils.

PMID- 17041738
TI  - Meningomyeloradiculitis as presenting feature of brucellosis.

PMID- 17041737
TI  - Characteristics associated with involuntary versus voluntary legal status at
      admission and discharge among psychiatric inpatients.
AB  - BACKGROUND: The objective of this analysis was to determine the ways in which
      patients' legal statuses at hospital admission and discharge are associated with
      select sociodemographic and clinical variables. This study specifically
      investigated differences between patients who were voluntary during both
      admission and discharge, patients who were involuntary on admission but voluntary
      on discharge (having converted to voluntary status during hospitalization), and
      patients who were involuntary during both admission and discharge. METHOD: Data
      were collected from the charts and treating clinicians of 227 consecutively
      discharged patients from two psychiatric units in a large, urban, county hospital
      in the southeastern United States. Based on results of bivariate tests,
      sociodemographic and clinical factors were entered into a polytomous logistic
      regression model to determine effect estimates (adjusted odds ratios). RESULTS:
      In the bivariate analyses, 15 variables were significantly associated with the
      trichotomous legal status. In the model, three factors were independently
      significantly associated with legal status, while controlling for four potential
      confounders: (1) whether or not the patient was experiencing psychotic symptoms
      at discharge, (2) whether or not the patient had documented medical problems
      requiring medication at discharge, and (3) the number of psychiatric medications.
      CONCLUSIONS: A generalized lack of treatment engagement and adherence among
      involuntary patients likely underlies significant differences between the groups
      in terms of psychotic symptoms, diagnosed medical problems requiring medications,
      and number of psychiatric medications at discharge. Studying legal status (and
      the process of legal status conversion from involuntary to voluntary) and its
      correlates is an important topic for further research.

PMID- 17041739
TI  - Frontal diaschisis in a German case of fatal familial insomnia.

PMID- 17041740
TI  - Differentiating Alzheimer's disease from subcortical vascular dementia with the
      FAB test.
AB  - BACKGROUND: The frontal assessment battery (FAB) test is a composite tool for
      assessing executive functions related to the frontal lobe. Neuropsychological and
      blood-flow studies indicate distinct patterns of deterioration of anterior and
      posterior cortical function in Alzheimer's disease (AD) and subcortical vascular
      dementia (VD) patients. We predict that the FAB score may be useful for
      discriminating VD from AD. OBJECTIVE: To evaluate the clinical usefulness of the
      FAB test for differential diagnosis of AD and VD. METHODS: We compared FAB scores
      in 25 patients with AD, 27 patients with VD, and 80 age-matched normal control
      subjects. The AD group was matched for age, education and MMSE score with the VD
      group. The subtest scores in FAB were also compared among the three groups.
      RESULTS: The FAB scores were significantly decreased in both the AD and VD groups
      compared to the control group, and the reduction were greater in the VD group.
      Among the FAB subtests, mental flexibility (phonological verbal fluency) was the
      only subtest that significantly discriminated VD from the other two groups.
      CONCLUSIONS: The FAB test can provide useful information for differentiating AD
      and VD at the bedside.

PMID- 17041742
TI  - Anomalous thermal denaturing of proteins adsorbed to nanoparticles.
AB  - We have used localized surface plasmon resonance (LSPR) to monitor the structural
      changes that accompany thermal denaturing of bovine serum albumin (BSA) adsorbed
      onto gold nanospheres of size 5nm-60nm. The effect of the protein on the LSPR was
      monitored by visible extinction spectroscopy. The position of the resonance is
      affected by the conformation of the adsorbed protein layer, and as such can be
      used as a very sensitive probe of thermal denaturing that is specific to the
      adsorbed protein. The results are compared to detailed calculations and show that
      full calculations can lead to significant increases in knowledge where gold
      nanospheres are used as biosensors. Thermal denaturing on spheres with diameter >
      20 nm show strong similarity to bulk calorimetric studies of BSA in solution. BSA
      adsorbed on nanospheres with d [Symbol: see text] 15nm shows a qualitative
      difference in behavior, suggesting a sensitivity of denaturing characteristics on
      local surface curvature. This may have important implications for other protein
      nanoparticle interactions.

PMID- 17041741
TI  - Impaired baroreflex function in temporal lobe epilepsy.
AB  - Changes of cardiovascular function are frequent in temporal lobe epilepsy (TLE).
      The baroreflex - the most important reflex for cardiovascular stability - has not
      been studied systematically in TLE. We evaluated cardiovascular variability and
      baroreflex function in TLE. In 22 TLE patients and 20 controls, we continuously
      monitored heart rate (HR) and blood pressure (BP). Time-domain parameters were
      derived from recordings at rest and from standard cardiovascular reflex tests.
      Spectral analysis determined sympathetic and parasympathetic modulation of HR and
      BP in the low (LF-power) and high frequency range (HF-power). We calculated the
      relative LF- and HF-powers of HR in relation to the sum of LF- and HF-powers.
      LF/HF-ratio of HR was assessed as a parameter of sympatheticovagal balance. LF
      transfer function gain between BP and HR determined baroreflex function.Time
      domain parameters did not differ between TLE patients and controls. Spectral
      analysis showed decreased absolute LF- and HF-powers but increased relative LF
      power and LF/HF-ratio of HR in TLE. LF-transfer function gain between BP and HR
      was reduced in TLE (p<0.05). The reduction of absolute LF- and HF-powers
      indicates decreased total autonomic variability in TLE. However, increased
      relative LF-power and LF/HF-ratio of HR in TLE show a relative increase of
      sympathetic tone. Most importantly, we demonstrate an impaired baroreflex
      function in TLE. These cardiovascular autonomic abnormalities may contribute to
      cardiac arrhythmia in TLE.

PMID- 17041743
TI  - Wormlike lipid/DNA micelles in a non-polar solvent.
AB  - The phase behavior of DOPE/DOTAP-DNA complexes in phase-separated
      oil(dodecane)/water mixtures was explored using Small Angle X-Ray Scattering
      (SAXS) and Fluorescence Correlation Spectroscopy (FCS). Inverse micelles of DNA
      with cationic-lipid coating were found in the oil phase. Varying the ratio
      between cationic and neutral lipids a transition from wormlike to spherical
      structures is observed for both long ( approximately 75000bp) and short (30
      1246bp) DNA. In contrast to lipid/DNA complexes in the water phase, there is no
      indication of condensed liquid-crystalline structures in the non-polar phase. In
      fact, FCS measurements on short DNA oligomers complexed with cationic lipid in
      alkane give clear evidence for monomeric inverse micelles of DNA. Dilution series
      revealed a critical lower concentration of lipids and DNA for observing lipid/DNA
      micelles.

PMID- 17041744
TI  - Sudden deterioration in nonclassical infantile-onset Pompe disease responding to
      alglucosidase alfa infusion therapy: a case report.
AB  - A patient with atypical infantile Pompe disease suffered acute respiratory
      insufficiency at the age of 8 years which resulted in complete immobilization and
      dependence on assisted ventilation. Shortly after initiation of enzyme
      replacement therapy, she regained her mobility and, after 20 months of treatment,
      she now leads an almost normal life with limited restrictions.

PMID- 17041745
TI  - The aetiology of neurological complications of organic acidaemias--a role for the
      blood-brain barrier.
AB  - The blood-brain barrier (BBB) metabolically isolates the central nervous system
      (CNS) from the circulation and protects it against fluctuations of hydrophilic
      nutrients in plasma and from intoxication. Recent studies have shown that
      dicarboxylic acids (DCAs) are transported across the blood-brain barrier at very
      low rates. In organic acidaemias, neurological complications are common. We
      hypothesize that, as a result of the very limited efflux, in certain organic
      acidaemias there is pathological accumulation of DCAs (e.g. glutarate, 3
      hydroxyglutarate, D-2- and L-2-hydroxyglutarate, methylmalonate) in the brain
      secondary to the metabolic block. At high concentrations some of these compounds
      may become neurotoxic. Treatment should be aimed at preventing the accumulation
      of these compounds using our understanding of the properties of the BBB.

PMID- 17041746
TI  - Mutational spectrum of classical galactosaemia in Spain and Portugal.
AB  - Classical galactosaemia is an autosomal recessive inherited metabolic disorder
      due to deficient galactose-1-phosphate uridyltransferase (GALT). Over 180
      different base changes and disease-causing mutations have been reported in the
      GALT gene. Mutation p.Q188R was found to be the most common molecular defect
      among caucasian classical galactosaemia patients. We have characterized the
      spectrum of GALT mutations in a group of 51 Spanish families and 32 Portuguese
      families with this disease. p.Q188R is also the most prevalent mutation in the
      Spanish and Portuguese population, accounting for 50% and 57.8% of galactosaemic
      alleles, respectively. An additional 15 mutations were also identified in Spanish
      patients, four of which were novel: p.D28H, p.S181A, c.658dupG and
      c.377+53_1059+87del. In the Portuguese population, 11 different mutations were
      found, three of which were novel: p.R33H, p.P185S, and p.S192G. The differences
      observed between the genotypes identified in Portuguese and Spanish galactosaemic
      populations are notable. Only mutations p.Q188R, p.R148Q and c.820+13g>a were
      identified in both populations. In spite of the geographical proximity of Spain
      and Portugal, it seems that they have received genetic influences from different
      populations. The repeated migrations that occurred in the Iberian Peninsula
      throughout centuries may explain such variability.

PMID- 17041747
TI  - Preclinical assessment of anthracycline cardiotoxicity in laboratory animals:
      predictiveness and pitfalls.
AB  - Doxorubicin is one of the most prescribed anticancer drugs, due to its important
      activity in hematological malignancies as in solid tumors. However, its important
      cardiac toxicity still limits its long-term use and prevents from reaching
      optimal benefits. Numerous ways have been proposed to avoid cardiac toxicity,
      such as protracted infusions or special formulations, development of less
      cardiotoxic analogues and of cardioprotectors. There is a need for preclinical
      models able to screen rapidly these various approaches and to provide rational
      bases for clinical trials. The first model is the long-term rabbit model.
      Weanling rabbits given weekly injections of doxorubicin for 4 months developed a
      cardiomyopathy which was obvious from a clinical (cardiac failure) and from a
      pathological point of view. This model has been widely used afterwards for the
      discovery of cardioprotective molecules. Models in other animals such as rats or
      mice were similarly implemented, also with long-term exposures to the drug,
      resulting in cardiac failure and severe pathological alterations which could be
      graded for comparison. Starting from the evidence that the damage caused by
      anthracyclines on cardiomyocytes was immediate after each injection and that the
      functional efficiency of the myocardium should be affected by the anthracyclines
      long before the morphological alterations become detectable, we developed a short
      term model studying the cardiac performances of isolated perfused hearts of rats
      that had been treated within 12 days by repetitive administrations of the
      molecule(s) to be tested. This model appeared easy to implement and provided the
      data expected from clinical experience: epirubicin appeared less cardiotoxic than
      doxorubicin; liposomal formulations appeared less cardiotoxic than free drug
      formulations; dexrazoxane strongly protected against doxorubicin cardiotoxicity.
      We were then to show that paclitaxel could potentiate doxorubicin cardiotoxicity,
      but that docetaxel did not so; or that a high dose of dexrazoxane brought
      significantly higher protection than a conventional dose. Based upon these
      various contributions, we can encourage the use of the short-term model of
      isolated perfused rat heart to screen the preclinical cardiotoxicity of
      anthracycline molecules, formulations and combinations.

PMID- 17041748
TI  - An evidence-based, multidisciplinary approach to the clinical considerations,
      management, and surveillance of adrenal lesions in familial adenomatous
      polyposis: report of three cases.
AB  - Adrenal masses are commonly discovered incidentally in patients with familial
      adenomatous polyposis, and adrenal malignancies have been rarely reported.
      Individuals with familial adenomatous polyposis frequently undergo abdominal CT
      scan examinations for surveillance or symptoms. Adrenal lesions often are
      detected unexpectedly and are thus becoming a common clinical problem in this
      population. Adrenal lesions encompass a heterogeneous spectrum of pathologic
      entities, including primary adrenocortical and medullary tumors, benign or
      malignant lesions, hormonally active or inactive lesions, metastases, and
      infections. When an adrenal mass is detected, the clinician needs to address two
      crucial questions: 1) is the mass malignant? and 2) is it hormonally active? This
      article presents three new cases of incidental adrenal lesions in familial
      adenomatous polyposis, reviews the medical literature for this setting, and
      provides an overview of the diagnostic clinical approach and management of the
      adrenal findings in familial adenomatous polyposis patients.

PMID- 17041749
TI  - Indication and benefit of pelvic sidewall dissection for rectal cancer.
AB  - PURPOSE: This study was designed to clarify indication and benefit of pelvic
      sidewall dissection for rectal cancer. METHODS: The retrospective, multicenter
      study collected the data of rectal cancer patients who underwent surgery between
      1991 and 1998 and were prospectively followed. RESULTS: Of 1,977 patients with
      rectal cancers, 930 underwent pelvic sidewall dissection without adjuvant
      radiotherapy. Positive lateral lymph nodes were found in 129. Multivariate
      analysis disclosed a significantly increased incidence of positive lateral lymph
      nodes in female gender, lower rectal cancers, non-well-differentiated
      adenocarcinoma, tumor size of > or =4 cm and T3-T4. The five-year survival rate
      for 1,977 patients was 79.7 percent. The survival of patients with positive
      lateral lymph nodes was significantly worse than that of Stage III patients with
      negative lateral lymph nodes (45.8 vs. 71.2 percent, P<0.0001). Multivariate
      analysis showed significantly worse prognosis in male gender, pelvic sidewall
      dissection, lower rectal cancers, T3-T4, perirectal lymph node metastasis, and
      positive lateral lymph nodes. During the median follow-up time of 57 months,
      recurrence developed in 19.7 percent: 17 percent in negative and 58.1 percent in
      positive lateral lymph nodes (P<0.0001). Local recurrence was found in 8 percent:
      6.8 percent in negative and 25.6 percent in positive lateral lymph nodes
      (P<0.0001). Multivariate analysis disclosed that lower rectal cancers, non-well
      differentiated adenocarcinoma, T3-T4, perirectal lymph node metastasis, and
      positive lateral lymph nodes were significantly associated with an increased
      local recurrence. CONCLUSIONS: Positive lateral lymph node was the strongest
      predictor in both survival and local recurrence. Pelvic sidewall dissection may
      be indicated for patients with T3-T4 lower rectal cancers because of the greater
      probability of positive lateral lymph nodes.

PMID- 17041750
TI  - Measurement of health-related quality of life in the early follow-up of colon and
      rectal cancer.
AB  - PURPOSE: Little is known about factors that affect health-related quality of life
      during the early follow-up of colorectal cancer. This study was designed to
      identify the factors that contribute to poor health-related quality of life after
      six weeks of follow-up and to compare the relative performance of instruments
      best suited to measure it. METHODS: A single-center, prospective study was
      designed to examine health-related quality of life after potentially curative
      surgery for colorectal cancer. Two condition-specific and two generic instruments
      (QLQ-C30, FACT-C, SF12 and EQ-5D) measured quality of life six weeks after
      discharge. Univariate and multivariate analyses were used to assess the impact of
      16 treatment factors, demographic variables, and symptoms on seven global health
      related quality of life scores. RESULTS: Questionnaires were obtained from 201
      consecutive patients. Five factors were associated with poor health-related
      quality of life scores at six-week follow-up in the multivariate analysis:
      reduced preoperative performance status, stomas, diarrhea, constipation, and
      younger than aged 65 years. No instrument out performed the others. However,
      condition-specific instruments and those in which patients subjectively rated
      their overall health-related quality of life were better suited to detect health
      related quality of life differences relating to the effects of colorectal cancer
      treatment. CONCLUSIONS: Younger patients, those with stomas, and those suffering
      from diarrhea or constipation are more likely to report poor health-related
      quality of life at six-week follow-up. The routine measurement of health-related
      quality of life using an instrument that includes a patient-rated scale together
      with condition-specific items could be used to detect patients at risk of poorer
      short-term health-related quality of life outcomes.

PMID- 17041751
TI  - Practice parameters for the prevention of venous thrombosis.

PMID- 17041752
TI  - Effect of aging on anorectal and pelvic floor functions in females.
AB  - PURPOSE: In females, fecal incontinence often is attributed to birth trauma;
      however, symptoms sometimes begin decades after delivery, suggesting that
      anorectal sensorimotor functions decline with aging. METHODS: In 61 asymptomatic
      females (age, 44 +/- 2 years, mean +/- standard error of the mean) without risk
      factors for anorectal trauma, anal pressures, rectal compliance, and sensation
      were assessed by manometry, staircase balloon distention, and a visual analog
      scale during phasic distentions respectively. Anal sphincter appearance and
      pelvic floor motion also were assessed by static and dynamic magnetic resonance
      imaging respectively in 38 of 61 females. RESULTS: Aging was associated with
      lower anal resting (r = -0.44, P < 0.001) and squeeze pressures (r = -0.32, P =
      0.01), reduced rectal compliance (i.e., r for pressure at half-maximum volume vs.
      age = 0.4, P = 0.001), and lower (P <or = 0.002) visual analog scale scores
      during phasic distentions at 16 (r = -0.5) and 24 mmHg (r = -0.4). Magnetic
      resonance imaging revealed normal anal sphincters in 29 females and significant
      sphincter injury, not associated with aging, in 9 females. The location of the
      anorectal junction at rest (r = 0.52, P < 0.001), squeeze (r = 0.62, P < 0.001),
      and Valsalva maneuver (r = 0.35, P = 0.03), but not anorectal motion (e.g., from
      resting to squeeze) was associated with age. CONCLUSIONS: In asymptomatic
      females, aging is associated with reduced anal resting and squeeze pressures,
      reduced rectal compliance, reduced rectal sensation, and perineal laxity.
      Together, these changes may predispose to fecal incontinence in elderly females.

PMID- 17041753
TI  - Fistulating anal Crohn's disease: results of combined surgical and infliximab
      treatment.
AB  - INTRODUCTION: Infliximab is a monoclonal antibody against tumor necrosis factor
      alpha, which has been shown to be effective in fistulating Crohn's disease. The
      safety of infliximab in patients with potential perianal sepsis is uncertain.
      This study was designed to assess the safety and outcome of infliximab therapy
      combined with surgery for patients with fistulating anal Crohn's disease.
      METHODS: All patients receiving infliximab for fistulating anal Crohn's disease
      between 2000 and 2004 were studied. Patients' demographics, clinical findings,
      magnetic resonance imaging, and examination under anesthesia were recorded.
      Perianal Crohn's disease activity index before and 8 to 12 weeks after three
      infusions of infliximab (5 mg/kg) were recorded. Routine policy was to insert
      drainage seton sutures at the time of preinfliximab examination under anesthesia
      and then remove it after the second infusion. Complications of treatment and
      outcome at the last clinic follow-up were recorded. RESULTS: Twenty-two patients
      underwent infliximab treatment (6 males; median age, 35 (range, 16-60) years).
      Twenty-one patients had preinfliximab examination under anesthesia: 12 required
      abscess drainage; 17 had at least one drainage seton suture inserted. Fourteen
      patients underwent pretreatment magnetic resonance imaging to identify clinically
      occult collections. All but one patient were established on immunomodulator
      therapy before infliximab treatment. Perianal Crohn's disease activity index
      improved significantly after infliximab infusion (preinfusion: median, 11, range,
      8-17; postinfusion: median, 8, range, 5-16; P<0.001). There were no serious
      complications of infliximab treatment. At median follow-up of 21 (range, 4-31)
      months, only four patients achieved sustained fistula healing. Five patients have
      required defunctioning or proctectomy. Four patients have required repeated
      infusions of infliximab. CONCLUSIONS: Infliximab therapy in combination with
      examination under anesthesia/seton drainage is a safe and effective short-term
      treatment for fistulating anal Crohn's disease. Long-term fistula healing rates
      are low.

PMID- 17041754
TI  - Epigallocatechin gallate induced apoptosis in Sarcoma180 cells in vivo: mediated
      by p53 pathway and inhibition in U1B, U4-U6 UsnRNAs expression.
AB  - The aim of this study was to understand the mode of action of tea polyphenol
      epigallocatechin gallate (EGCG) in vivo. Swiss albino mice were treated i.p. with
      EGCG at two different doses i.e. 12-mg/kg body weight and 15-mg/kg body weight,
      for 7 days prior to inoculation of Sarcoma180 (S180) cells and continued for
      another 7 days. The growth of the S180, harvested 7 days after inoculation, was
      significantly reduced due to treatment with EGCG. The flowcytometric analysis of
      S180 cells, showed significant increase in apoptosis and reduction in the number
      of cells in G2/M phase of cell cycle due to treatment with EGCG. The induction of
      apoptosis has also been confirmed by the TUNEL and DNA fragmentation assays. Both
      RT-PCR and Western blot analysis showed significant up-regulation of p53 and bax,
      and down-regulation of bcl-2 and c-myc due to EGCG treatment. No changes in the
      expression pattern of p21, p27, bcl-xl, mdm2 and cyclin D1 were seen.
      Interestingly, there was significant down-regulation of spliceosomal uridylic
      acid rich small nuclear RNAs (UsnRNAs) U1B and U4-U6 due to EGCG treatment. This
      indicates that these UsnRNAs may be involved in the apoptosis process. Taken
      together, our study suggests that in vivo EGCG could induce apoptosis in S180
      cells through alteration in G2/M phase of the cell cycle by up-regulation of p53,
      bax and down-regulation of c-myc, bcl-2 and U1B, U4-U6 UsnRNAs.

PMID- 17041755
TI  - Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis
      through NF-kappaB activation.
AB  - We have previously shown that UEV1 is up-regulated in all tumor cell lines
      examined and when SV40-transformed human embryonic kidney cells undergo
      immortalization; however, it is unclear whether and how UEV1 plays a critical
      role in this process. UEV1A encodes a ubiquitin conjugating enzyme variant, which
      is required for Ubc13 (ubiquitin conjugating enzyme) catalyzed poly
      ubiquitination of target proteins through Lys63-linked chains. One of the target
      proteins is NEMO/IKKgamma (nuclear factor-kappaB essential modulator/inhibitor of
      kappaB protein kinase), a regulatory subunit of IkappaB kinase in the NF-kappaB
      signaling pathway. In this report, we show that constitutive high-level
      expression of UEV1A alone in cultured human cells was sufficient to cause a
      significant increase in NF-kappaB activity as well as the expression of its
      target anti-apoptotic protein, Bcl-2 (B-cell leukemia/lymphoma 2). Overexpression
      of UEV1A also conferred prolonged cell survival under serum-deprived conditions,
      and protected cells against apoptosis induced by diverse stressing agents. All of
      the effects of Uev1A were reversible upon suppression of UEV1 expression by RNA
      interference. Our observations presented in this report provide evidence that
      Uev1A is a critical regulatory component in the NF-kappaB signaling pathway in
      response to environmental stresses and identify UEV1A as a potential proto
      oncogene.

PMID- 17041757
TI  - Apoptosis promoted by up-regulation of TFPT (TCF3 fusion partner) appears p53
      independent, cell type restricted and cell density influenced.
AB  - The TFPT/FB1 gene was identified because of its involvement in childhood pre-B
      acute lymphoblastic leukaemia (ALL). Although its specific function is still
      unclear, Tfpt has been implicated in cell proliferation and induction of
      programmed cell death (PCD). Given the critical role of PCD in leukemogenesis, we
      have investigated the responsiveness of different cell lines to TFPT over
      expression and the consequent induction of PCD by proliferation kinetic analysis,
      immunolocalization and TUNEL assay. We have also tested the involvement of
      factors implicated in cell cycle progression and apoptosis, i.e. caspases, p53,
      Cdc2. Our results indicate that over expression of TFPT promotes caspase 9
      dependent apoptosis, nevertheless the apoptotic cascade is engaged only in
      culture conditions sustaining cell proliferation and different cell lines display
      differential responsiveness to TFPT induced apoptosis Although p53 is a main
      regulator of apoptosis in mammalian cells, the Tfpt induced apoptosis appears p53
      independent. These results are discussed relatively to the role played by TFPT in
      leukemogenesis.

PMID- 17041756
TI  - Signaling through the TRAIL receptor DR5/FADD pathway plays a role in the
      apoptosis associated with skeletal myoblast differentiation.
AB  - Apoptosis rather than differentiation is a physiological process during
      myogenesis and muscle regeneration. When cultured myoblasts were induced to
      differentiate, we detected an increase in caspase 8 activity. Pharmacological
      inhibition of caspase 8 activity decreased apoptosis. Expression of a dominant
      negative mutant of the adapter protein FADD also abrogated apoptosis, implicating
      a death ligand pathway. Treatment with TRAIL, but not Fas, induced apoptosis in
      these myoblasts. Accordingly, treatment with a soluble TRAIL decoy receptor or
      expression of a dominant-negative mutant of the TRAIL receptor DR5 abrogated
      apoptosis. While TRAIL expression levels remained unaltered in apoptotic
      myoblasts, DR5 expression levels increased. Finally, we also detected a reduction
      in FLIP, a death-receptor effector protein and caspase 8 competitive inhibitor,
      to undetectable levels in apoptotic myoblasts. Thus, our data demonstrate an
      important role for the TRAIL/DR5/FADD/caspase 8 pathway in the apoptosis
      associated with skeletal myoblast differentiation. Identifying the functional
      apoptotic pathways in skeletal myoblasts may prove useful in minimizing the
      myoblast apoptosis that contributes pathologically to a variety of diseases and
      in minimizing the apoptosis of transplanted myoblasts to treat these and other
      disease states.

PMID- 17041758
TI  - Syndecan-2 expression increases serum-withdrawal-induced apoptosis, mediated by
      re-distribution of Fas into lipid rafts, in stably transfected Swiss 3T3 cells.
AB  - To examine the function of syndecan-2, one of the most abundant heparan sulfate
      proteoglycans in fibroblasts, we obtained stably transfected Swiss 3T3 clones. We
      examined the effects of stable syndecan-2 overexpression on programmed cell
      death, finding that syndecan-2 transfected cells were more sensitive to apoptosis
      induced by serum-withdrawal than control cells. In addition, overexpression of
      syndecan-2 correlates with increased membrane levels of the Fas/CD95 receptor,
      suggesting that the increased serum-withdrawal apoptosis observed in Swiss 3T3
      cells might be Fas receptor-dependent. Differences in Fas membrane levels between
      both control and syndecan-2 transfected cells result from a redistribution of the
      Fas receptor. Our data clearly demonstrate that increased Fas levels are
      primarily related to lipid rafts and that this increase is a key factor in
      Fas/CD95-mediated apoptosis. Moreover, disruption of lipid rafts with methyl-beta
      cyclodextrin or filipin significantly reduced apoptosis in response to serum
      withdrawal. The differences in Fas/CD95 membrane distribution could explain why
      syndecan-2 transfected cells have a higher susceptibility to serum-withdrawal
      induced apoptosis.

PMID- 17041759
TI  - Norepinephrine induces apoptosis in neonatal rat endothelial cells via a ROS
      dependent JNK activation pathway.
AB  - Our previous study demonstrated that norepinephrine (NE) induces endothelial
      apoptosis mainly through down-regulation of Bcl-2 protein and activation of the
      beta-adrenergic and caspase-2 pathways. However, whether reactive oxygen species
      (ROS) and mitogen-activated protein kinases (MAPKs) are involved in this signal
      transduction remains unknown. Endothelial cells cultured from neonatal rat heart
      were treated with 100 microM NE. Proteins of MAPKs and Bcl-2 family were assayed
      by Western blotting. Apoptosis was determined by terminal deoxynucleotidyl
      transferase-mediated nick end-labeling assay. ROS was analyzed with flow
      cytometry. Caspase activity was measured using specific fluorogenic substrates.
      Treatment with NE increased intracellular ROS level and extracellular signal
      regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 phosphorylation.
      Whereas the phosphorylated form of Akt was decreased. The NE-induced apoptosis
      was abrogated by SP600125 (a specific inhibitor of JNK). Antioxidants such as
      vitamin C and N-acetyl cysteine inhibited NE-induced ROS production, JNK
      phosphorylation, caspase activation and apoptosis. Exogenously added superoxide
      dismutase or catalase markedly diminished NE-induced ROS production and cell
      death. In conclusions, our study is the first report documenting that NE induces
      apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation
      pathway. Antioxidants may be useful in the prevention and management of NE
      mediated endothelial apoptosis during heart failure.

PMID- 17041761
TI  - Quantitative assessment of mitral insufficiency: its advantages and
      disadvantages.

PMID- 17041762
TI  - Pathophysiology of ischemic mitral insufficiency: does repair make a difference?

PMID- 17041763
TI  - Is ischemic mitral regurgitation an indication for surgical repair or
      replacement?
AB  - Ischemic mitral regurgitation (IMR) is common in patients with coronary artery
      disease. While it is well-known that IMR exerts a graded effect upon survival-the
      greater the degree of IMR, the lower the survival-the indications for surgical
      treatment and the choice of surgical procedure (repair versus replacement) are
      controversial. In patients with mild to moderate IMR, the benefit of a mitral
      valve procedure has not been demonstrated, and surgical practice varies. In
      patients with severe IMR, mitral valve surgery is the norm, but guidelines for
      choosing between valve repair and valve replacement do not exist. Furthermore,
      the survival impact of mitral valve surgery in patients with severe IMR is
      uncertain. When patients with severe IMR undergo mitral valve surgery, undersized
      annuloplasty results in durable repair in 70% to 85% of cases. Newly-developed
      adjunctive repair techniques may further improve results. Currently, mitral valve
      repair is the procedure of choice in the majority of patients having surgery for
      severe IMR. However, the most severely ill patients and those with certain
      echocardiographic characteristics (e.g. severe bileaflet tethering) should be
      treated with bioprosthetic mitral valve replacement rather than repair.

PMID- 17041764
TI  - Current concepts in mitral valve repair for degenerative disease.

PMID- 17041765
TI  - New techniques for percutaneous repair of the mitral valve.
AB  - A variety of innovative techniques and devices are being developed for the
      percutaneous management of mitral insufficiency. More than 30 devices are in
      stages of development from early stage to human pivotal trials. Two devices for
      the management of degenerative myxomatous disease of the mitral valve replicate
      the Alfieri edge-to-edge surgical repair. One of those devices, the Evalve
      Mitraclip, is in a pivotal trial at the current time. The other devices address
      functional mitral regurgitation by a variety of techniques for performing mitral
      valve annuloplasty. The majority of devices take advantage of the proximity of
      the coronary sinus to the posterior mitral annulus to deliver devices that
      remodel the mitral annulus. Two devices perform septal lateral cinching
      decreasing the anterior posterior diameter of the mitral annulus and correcting
      leaflet malcoaptation. Numerous issues are discussed including regulatory hurdles
      and the integration of percutaneous techniques into clinical practice in a safe
      and efficacious manner.

PMID- 17041767
TI  - [Doctor shopping: the difficult-to-manage patient].
AB  - Medically unexplained symptoms and bodily dysfunctions are the single most
      prevalent class of symptoms in primary care. Differences in opinion as to the
      cause of the illness between the patients and the health care professionals make
      somatoform disorders a challenge for the patient-doctor relationship, and
      frequently produce negative feelings in health care professionals. The patients
      are usually reluctant to consider psychosocial aspects of their illness to be a
      factor. Early recognition of patients with somatization tendencies would be
      beneficial so that more effective treatment could begin sooner and unnecessary
      treatment be avoided. In order not to reinforce the patient's symptomatology,
      physicians should schedule appointments in a time contingent rather than a
      symptom contingent manner. Repetition of different tests should be avoided
      despite patients' demands in order not to further exacerbate the disorder. In
      many patients, psychotherapy should be recommended, although motivational work
      should already be initiated at the primary care stage.

PMID- 17041768
TI  - [Functional gastrointestinal disorders].
AB  - The functional gastrointestinal disorders (FGID) are the most frequent clinical
      conditions seen in practice. The FGID are associated with significant work
      absenteeism, impaired quality of life and increased medical costs. Most patients
      also suffer from psychosocial problems. Therefore it is important to define the
      patient's complaints in terms of a biopsychosocial disorder rather than just a
      medical illness. Physicians must acknowledge the relevance of the psychosocial
      aspects to prepare the patient for a referral to a specialist (in psychosomatic
      medicine or a psychotherapist) and to get the patient interested in the
      psychological factors involved as well as further explore their cause. Most of
      the research on psychotherapy in FGID to date has focused on the irritable bowel
      syndrome, and different methods of treatments have been studied (e. g., cognitive
      behavioral therapy, dynamic psychotherapy, hypnotherapy, and relaxation).
      Randomised controlled studies have shown that psychotherapy is superior to
      conventional medical therapy. Hypnotherapy seems to be very successful.
      Predictors of a positive response to psychological treatment generally are: (1)
      awareness that stress exacerbates their bowel symptoms, (2) mild anxiety or
      depression, (3) the predominant bowel symptom is abdominal pain or diarrhea and
      not constipation, (4) the abdominal pain waxes and wanes in response to eating,
      defecation, or stress rather than being constant pain, and (5) the symptoms are
      of relatively short duration. Psychotherapy is initially relatively expensive
      because it requires multiple, long sessions. However, its benefits persist or
      even increase over time, and in the long run, there may be a reduction in clinic
      visits and health care costs which offsets the initial cost of psychological
      treatment.

PMID- 17041769
TI  - [When health care professionals become unwillingly involved in child abuse: the
      Munchhausen-by-proxy syndrome].
AB  - Reports on seemingly caring mothers, who at the same time fabricate or provoke
      clinical symptoms in their children and subsequently expose them to potentially
      harmful medical procedures, are hardly believable at first sight. Nevertheless
      the steadily growing number of reports on this kind of child abuse, known as
      Munchausen-by-proxy syndrome, points to a significant number of undetected cases.
      The interactional involvement of health care professionals in the abuse tends to
      impede diagnosis, and, as a consequence of the syndrome, usually leads to violent
      emotional reactions, which require careful analysis and professional handling.

PMID- 17041770
TI  - [Medical quality circles for drug replacement therapy].
AB  - Drug replacement therapy using synthetic opioids is in Vienna mostly carried out
      by primary care physicians. Group teaching in quality assurance groups has been
      installed in order to give these doctors the necessary personal and informational
      assistance. Evaluation has shown that: 1. 90% of the doctors were highly or well
      satisfied with the teaching. Only 10% were slightly critical. 2. They could
      better communicate with, and were able to show more tolerance towards, the
      "difficult" patients. 3. Specialized knowledge increased (risk of infection,
      "management of hepatitis", contact with authorities, co-medication). 4. Some
      critical remarks pointed towards ways in which this particular further education
      could in future be better organized and dealt with more intensively.

PMID- 17041771
TI  - [On the function of beta3-adrenoceptors in the human heart: signal transduction,
      inotropic effect and therapeutic prospects].
AB  - Beta-adrenergic stimulation is an important regulatory mechanism of cardiac
      function. Next to beta1- and beta2-adrenoceptors, the expression of a third beta
      adrenoceptor population, the beta3-adrenoceptor, has recently been evidenced in
      the human heart. Stimulation of cardiac beta3-adrenoceptors leads to a decrease
      in contractility via a release of nitric oxide (NO). In this context, different
      molecular mechanisms of endothelial nitric oxide synthase (eNOS) activation have
      been uncovered to occur as a consequence of beta3-adrenergic stimulation. In both
      nonfailing and failing myocardium, beta3-adrenergic stimulation may have a
      protective effect against excessive chatecolaminergic stimulation as it occurs
      during somatic and mental stress and during heart failure. For this reason, the
      beta3-adrenoceptor is discussed as a possible target for the pharmacological
      therapy of heart failure.

PMID- 17041773
TI  - [Histopathological diagnostics in endoprosthesis loosening].
AB  - The implantation of total joint endoprostheses has become a routine procedure,
      being executed about 1.5 million times per year worldwide. The indications are
      osteoarthritis, rheumatic diseases, trauma and bone neoplasia. However, about 5
      12% of patients develop pain and impaired function of the endoprosthesis within
      10 years, necessitating revision surgery. During this operation, the so-called
      periprosthetic membrane between bone and prosthesis is removed. This connective
      tissue membrane has a pathogenetic impact on the loosening process and can be
      evaluated by histopathology. This article aims at elucidating the defined
      histomorphological criteria for the standardized diagnostics of periprosthetic
      membranes using a recently established classification system.

PMID- 17041774
TI  - [Histopathological examination of joint degeneration: typing, grading and staging
      of osteoarthritis].
AB  - Degenerative arthropathy (osteoarthritis) is one of the most common diseases in
      modern western societies, in particular in the elderly. The classification and
      grading of changes during cartilage degeneration represent complex endeavors
      which are only of limited value in daily pathological practice. In general, the
      process of joint destruction can always be evaluated for the determining
      pathogenesis ("typing"), extent ("staging") and degree of the most extensive
      focal damage ("grading"). However, for routine use one might best restrict
      description and reporting to the most essential features. This is in particular
      true for specimens obtained from endoprosthetic surgery (hips and knees), because
      there is currently no specific clinical relevance for further evaluation. Only
      the identification of secondary types of degenerative changes, such as those due
      to unknown rheumatoid disease, gout or extensive osteonecrosis, is of particular
      interest to the clinical colleague (i.e. typing of the joint lesion).

PMID- 17041775
TI  - [Histopathology of space-occupying lesions of the spine].
AB  - The first step in diagnosing spinal lesions is to define the anatomical location,
      especially via magnetic resonance tomography, which is also helpful for
      histopathologists. However, definite diagnosis is based on histologic and
      cytologic examinations especially in the case of fine-needle biopsies. In this
      short review the principal histopathologic diagnoses of primary and secondary
      tumors and tumor-like lesions of the spine itself, the epidural space, the spinal
      meninges and nerve roots, and the spinal cord are addressed. The significance of
      immunohistochemistry for differential diagnosis or, in cases of spinal
      metastasis, for determination of the primary is discussed.

PMID- 17041776
TI  - [Quality assessment according to DIN EN ISO 9001:2000: certification in a
      university ENT department].
AB  - BACKGROUND: In 2003, our department inaugurated a quality management system. The
      certification according to DIN EN ISO 9001:2000 as required by the hospital
      management was achieved in August 2005. The aims were optimization of internal
      operating schedules and standardization of procedures according to logistic
      interfaces with external structures. METHODS: Since 2000, the implementation of
      an internal quality management system is required by German law and threatened by
      penalty in case of non-implementation. Beside a basic audit and optimization of
      all organizational procedures, all core processes were determined and the
      approvals checked. These aims involve both the quality of operational procedures,
      in and outpatient treatment, research, study and teaching and aspects of service
      such as quickness of scheduling and forwarding of reports as well as economic
      aspects and efficiency. The department of "quality management", whose main tasks
      are the professional guidance and the training of the quality management
      representatives, plays an important role. RESULTS: Realization of the new
      regulations and restructuring resulted in an increase in effectiveness and an
      improvement in operational procedures. In particular, patients and staff have
      benefited from the reorganized and modified sequence of operations. CONCLUSION:
      Implementation of a quality management system in different hospital departments
      is recommended.

PMID- 17041778
TI  - [New developments in navigation technology].

PMID- 17041777
TI  - [Hyperplastic scars and keloids. Part I: basics and prevention].
AB  - Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and
      keloid formation, causing functional and cosmetic deformities, discomfort,
      psychological stress, and patient dissatisfaction. Scar prevention and management
      continue to be important issues for the facial plastic surgeon. This article
      presents an overview on the pathogenesis of a scar and of the different types of
      scars. Differences between keloids, hypertrophic scars and normal scars include
      distinct scar appearance, histologic morphology and cellular function in response
      to growth factors. Recent advances in our understanding of the wound healing
      process reveal possible causes for hypertrophic scars and keloids. This
      information might assist in the development of efficacious prevention and
      treatment for hypertrophic scar and keloid formation. This article also describes
      the strategies available for scar prevention. Recommendations focus on the
      management of hypertrophic scars and keloids.

PMID- 17041779
TI  - [Management of iatrogenic esophageal perforations].
AB  - BACKGROUND: Iatrogenic esophageal perforations are still a life-threatening
      clinical entity. PATIENTS AND RESULTS: We present the case reports of six
      patients to demonstrate different treatment options and we focus on new
      therapeutic strategies which have evolved in the interdisciplinary management of
      iatrogenic esophageal perforations. Two patients with perforations in the
      cervical esophagus were operated and in another patient the perforation was
      closed with fibrin glue. Three patients with perforations in the thoracic
      esophagus were treated with self-expandable plastic stents. CONCLUSION: The
      surgical therapy of esophageal perforations still is regarded to be the gold
      standard and nonadherence should only be considered based on interdisciplinary
      decisions in individual cases. However, positive results are increasingly being
      reported for conservative endoscopic treatment, particularly for thoracic
      perforations.

PMID- 17041780
TI  - [Diagnosis and therapy of auditory synaptopathy/neuropathy].
AB  - Pathological auditory brainstem responses (lack of responses, elevated thresholds
      and perturbed waveforms) in combination with present otoacoustic emissions are
      typical audiometric findings in patients with a hearing impairment that
      particularly affects speech comprehension or complete deafness. This heterogenous
      group of disorders first described as "auditory neuropathy" includes dysfunction
      of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or
      of the generation and propagation of action potentials in the auditory nerve
      (neuropathy). This joint statement provides prevailing background information as
      well as recommendations on diagnosis and treatment. The statement focuses on the
      handling in the german language area but also refers to current international
      statements.

PMID- 17041782
TI  - Calcium-sensing receptor stimulation induces nonselective cation channel
      activation in breast cancer cells.
AB  - The calcium-sensing receptor (CaR) is expressed in epithelial ducts of both
      normal human breast and breast cancer tissue, as well as in the MCF-7 cell line
      as assessed by immunohistochemistry and Western blot analysis. However, to date,
      there are no data regarding the transduction pathways of CaR in breast cancer
      cells. In this study, we show that a CaR agonist, spermine, and increased
      extracellular Ca(2+) ([Ca(2+)](o)) sequentially activate two inward currents at 
      80 mV. The first was highly permeable to Ca(2+) and inhibited by 2-aminophenyl
      borate (2-APB). In contrast, the second was more sensitive to Na(+) and Li(+)
      than to Ca(2+) and insensitive to 2-APB. Furthermore, intracellular dialysis with
      high Mg(2+), flufenamic acid or amiloride perfusion was without any effect on the
      second current. Both currents were inhibited by La(3+). Calcium imaging
      recordings showed that both [Ca(2+)](o) and spermine induced an increase in
      intracellular calcium ([Ca(2+)](i)) and that removal of extracellular Ca(2+) or
      perfusion of 2-APB caused a decline in [Ca(2+)](i). It is well known that
      stimulation of CaR by an increase in [Ca(2+)](o) or with spermine is associated
      with activation of phospholipase C (PLC). Inhibition of PLC reduced the
      [Ca(2+)](o)-stimulated [Ca(2+)](i) increase. Lastly, reverse-transcriptase
      polymerase chain reaction showed that MCF-7 cells expressed canonical transient
      receptor potential (TRPCs) channels. Our results suggest that, in MCF-7 cells,
      CaR is functionally coupled to Ca(2+)-permeable cationic TRPCs, for which TRPC1
      and TRPC6 are the most likely candidates for the highly selective Ca(2+) current.
      Moreover, the pharmacology of the second Na(+) current excludes the involvement
      of the more selective Na(+) transient receptor potential melastatin (TRPM4 and
      TRPM5) and the classical epithelial Na(+ )channels.

PMID- 17041781
TI  - COPI-mediated transport.
AB  - COPI-coated vesicles are protein and liquid carriers that mediate transport
      within the early secretory pathway. In this Topical Review, we present their main
      protein components and discuss current models for cargo sorting. Finally, we
      describe the striking similarities that exist between the COPI system and the two
      other characterized types of vesicular carriers: COPII- and clathrin-coated
      vesicles.

PMID- 17041784
TI  - Vitamin C pretreatment attenuates hypoxia-induced disturbance of sodium currents
      in guinea pig ventricular myocytes.
AB  - As an important in vivo antioxidant, vitamin C is commonly used clinically to
      alleviate hypoxia-induced heart symptoms. To approach the protective mechanisms
      of vitamin C on hearts during hypoxia, we investigated the electrophysiological
      effects of vitamin C (1 mM: , pretreated before hypoxia) on Na(+) currents
      (including transient and persistent Na(+) currents) in guinea pig ventricular
      myocytes during hypoxia by the whole-cell and single-channel patch-clamp
      techniques. Whole-cell recordings showed that the mean current density of I (NaT)
      in the hypoxia group decreased from the control value of 40.2142 +/- 1.7735 to
      27.1663 +/- 1.8441 pA/pF and current density of I (NaP) increased from 0.3987 +/-
      0.0474 to 1.1854 +/- 01994 pA/pF (n = 9, P < 0.05 vs. control) at 15 min.
      However, when vitamin C was administered before hypoxia as pretreatment, I (NaT
      )and I (NaP )varied moderately (mean current density of I (NaT) decreasing from
      41.6038 +/- 2.9762 to 34.6341 +/- 1.9651 pA/pF and current density of I (NaP)
      increasing from 0.3843 +/- 0.0636 to 0.6734 +/- 0.1057 pA/pF; n = 9, P < 0.05 vs.
      hypoxia group). Single-channel recordings (cell-patched) showed that the mean
      open probability and open time of I (NaP) increased significantly in both groups
      at hypoxia 15 min. However, the increased current values of the hypoxia group
      were still marked at hypoxia 15 min (n = 9, P < 0.05 vs. vitamin C + hypoxia
      group). Our results indicate that vitamin C can attenuate the disturbed effects
      of hypoxia on Na(+) currents (I (NaT) and I (NaP)) of cardiac myocytes in guinea
      pigs effectively.

PMID- 17041785
TI  - A compromise method to facilitate under-represented minority admissions to
      medical school.
AB  - Ranked purely on the basis of the available reliable and valid measures, the
      demographic composition of incoming medical students fails to meet societal
      concerns regarding under-represented minorities (URM). Admissions offices are
      squeezed, administratively and legally, between honouring objectively measured
      individual merit and addressing societal needs. Until more successful recruitment
      and preparation of URM applicants closes that gap, compromise methods balancing
      those discordant ideals can be applied. Indeed, as progress over time decreases
      the relative societal need for affirmative action, compromise methods are
      mandated by no less a voice than that of the United States Supreme Court. This
      article proffers one such method, based upon the work of Hofstee, and
      demonstrates how it can be practically applied to a specific URM challenge. As
      perspective, past and present philosophical approaches to this discordance are
      categorized.

PMID- 17041783
TI  - Expression and functional characterization of the human ether-a-go-go-related
      gene (HERG) K+ channel cardiac splice variant in Xenopus laevis oocytes.
AB  - HERG C(Cardiac), a C-terminal splice variant of the human ether-a-go-go-related
      gene (HERG A), was identified and found to be 100% homologous to HERG(USO). Real
      time polymerase chain reaction data indicated that in the human heart HERG
      C(Cardiac )mRNA was expressed eight times more than HERG A, whereas in human
      ventricular tissue it was expressed six times more than HERG A. A HERG C(Cardiac)
      green fluorescence protein (GFP) construct was heterologously expressed in
      Xenopus oocytes. Confocal micrographs revealed that HERG C(Cardiac )was mainly
      expressed in the plasma membrane. HERG C(Cardiac) channel expressed in oocytes
      produced slower inactivating outward currents and faster deactivating tail
      currents than those of HERG A channel. Equal amounts of HERG A and HERG
      C(Cardiac) cRNA coinjected into oocytes formed intermediate HERG A + HERG
      C(Cardiac) heteromultimers, which was reconfirmed by immunoprecipitation
      experiments with a HERG A N-terminal antibody. These heteromultimers had
      different inactivation, deactivation and activation kinetics from those of HERG A
      and HERG C(Cardiac) channels. HERG A + HERG C(Cardiac) heteromultimers
      significantly reduced the model action potential mean amplitude and increased the
      fast and slow inactivation tau values of the action potential repolarization
      phase, suggesting involvement of HERG A and HERG C(Cardiac) heteromultimers in
      modulation of the refractory interval.

PMID- 17041786
TI  - An innovative pharmaceutical care practical course.
AB  - The innovative practical course was developed to improve the students' ability to
      acquire pharmaceutical care skills. The primary components of the course were in
      school training using small group discussions and hospital experience including
      identification, analysis, prevention and resolution of drug-therapy problems,
      patient counseling on their medications and diseases, and interaction with
      medical team. Specific objectives of the research were to (1) compare students'
      performance before and after the course, (2) measure students' perceptions of
      their pharmaceutical care skills before and after the course, (3) determine
      students' perception of the value of the course. Statistical comparison of pre
      test and post-test grades indicated both a retention and acquiring pharmaceutical
      care skills. A pre-course and post-course survey instrument was designed to
      measure students' perception of their pharmaceutical care skills. Perception of
      most of the items of the survey was significantly improved at the end of the
      course. Overall, the majority of students were highly satisfied with the course.
      In conclusion, the present study demonstrates that the innovative pharmaceutical
      care practical course was successfully introduced.

PMID- 17041787
TI  - Medical student attendance at non-compulsory lectures.
AB  - The General Medical Council in the UK recommends that undergraduate medical
      students be exposed to a variety of learning opportunities and increasingly take
      responsibility for their own learning. This study presents quantitative and
      qualitative data relating to attendance at non-compulsory plenary lectures in
      order to understand factors affecting the value placed by students on this
      component of the first 2 years of a contemporary medical curriculum. Attendance
      data were available for 87% first year and 78% second year plenary lectures.
      There was no difference in attendance at lectures that were delivered
      telematically to a remote site when compared with those where the speaker was
      present. There were markedly more students attending lectures at the beginning of
      the first academic year, with numbers decreasing as the year progressed. More
      first year students attended lectures on biomedical science and clinically
      focussed topics than on human science and public health whereas second year
      student attendance was similar across topics. Reasons given for non-attendance at
      plenary sessions fell into "student-related" factors (e.g. dislike of lecture
      based learning) and "teaching-related" factors (e.g. perceived variable quality
      of lectures). This study confirms that some students value lectures highly as a
      method to supplement other learning opportunities, whereas others find they learn
      better by other means.

PMID- 17041788
TI  - A multi-level assessment of a program to teach medical students to teach.
AB  - Few longitudinal programs exist to teach senior students (MS4s) to be teachers,
      nor have there been any reports of comprehensive program evaluation in this area.
      The primary objectives of this study were to describe our ongoing faculty
      development effort and to develop a multi-level program evaluation, using Dixon's
      model. The TALKS (Teaching and Learning Communication Skills) program is a senior
      elective and open to all MS4s. We evaluated our program through assessment of its
      participants at three levels: level 1, opinion; level 2, competence; and level 3,
      performance; but not level 4, patient outcomes. The authors used a retrospective,
      pre-post questionnaire to assess MS4 attitudes about their educational
      experiences, a traditional instrument to assess their teaching, an interaction
      analysis technique using Bloom's taxonomy to assess MS4s' feedback skills, and a
      SP exam to assess MS4 communication skills. The authors hypothesized that MS4s
      participating in TALKS would view medical education more positively and
      informatively, would demonstrate important principles in giving feedback, would
      be assessed as excellent teachers, and would perform better than controls in an
      SP exam emphasizing communication skills. Results revealed that MS4s' ratings as
      teachers were very good to excellent, with the highest scores on the items
      "knowledgeable, supportive of me, and answering questions clearly." (Level 1,
      Opinion) MS4s' perceptions of their knowledge, attitudes and skills increased
      significantly from the pre to the post-questionnaire. (Level 2, Competence) MS4
      feedback skills to MS2s revealed they did more talking than ideal, often at the
      lowest levels of Bloom's taxonomy. (Level 3, Performance) MS4s demonstrated
      better communication skills than controls on an evaluation by professional SPs.
      (Level 3, Performance).

PMID- 17041789
TI  - Demography of aging in China and the United States and the economic well-being of
      their older populations.
AB  - Today China has the world's largest older population, defined as aged 65 and
      over. The size of the older population in the United States is also large,
      ranking third in the world in 2000. The combined older populations of China and
      the United States represented 29 percent of the world's population 65 and older
      in 2000. The large older populations in these two countries are projected to more
      than double in size over the next three decades. Although currently China is
      younger than the United States and many other countries, its aging process will
      accelerate in the next few decades, with a speed surpassing the experience of
      many Western European countries and the United States. This paper examines the
      current and future situation of the older population in China and compares
      China's aging with that of the United States, using 2000 and earlier censuses
      from both countries as well as the population projections data from the U.S.
      Census Bureau. Growth of the older population, changes in the age distribution in
      China with comparisons to the United States, and the projections of the older
      population's future growth are analyzed and presented. The paper also discusses
      sources of financial support and living arrangements in China and the United
      States. Finally, the paper assesses trends in the older population support ratio
      and the implications for the economic well-being of an aging population.

PMID- 17041791
TI  - Acute and late genitourinary toxicity of conformal radiotherapy for prostate
      cancer.
AB  - PURPOSE: The aim of this study was to identify predictive factors for
      genitourinary (GU) toxicity in prostate cancer patients who underwent conformal
      radiotherapy (CRT). MATERIALS AND METHODS: In this study we analyzed 154 cases of
      T1-3N0M0 prostate adenocarcinoma and evaluated the occurrence rate of acute and
      late GU toxicity and the duration of acute toxicity according to clinical
      parameters: age, transurethral resection of the prostate prior to CRT, hormone
      therapy, CRT dose, length of planning target volume (PTV). RESULTS: Altogether,
      41% of the patients developed grade 2 or higher acute GU toxicity. Longer PTV was
      significantly associated with a higher incidence of acute GU toxicity (>7 cm,
      53%; <or=7 cm, 31%; P = 0.003), and hormone therapy prolonged the duration of the
      toxicity (P = 0.007). Grade 1 or higher late GU toxicity developed in 23% of the
      patients, and the 2-year late GU toxicity-free survival rate was 79%. Acute GU
      toxicity was significantly associated with the late GU toxicity-free survival
      rate (grade 0-1, 88.7%; grade 2-4, 73.2%; P = 0.0007). CONCLUSION: The length of
      PTV and hormone therapy were predictive factors for acute GU toxicity.
      Furthermore, acute GU toxicity was the most important predictive factor for late
      GU toxicity.

PMID- 17041790
TI  - Moisture-induced aggregation of lyophilized DNA and its prevention.
AB  - PURPOSE: To investigate the moisture-induced aggregation (i.e., a loss of
      solubility in water) of DNA in a solid state and to develop rational strategies
      for its prevention. METHODS: Lyophilized calf thymus DNA was exposed to relative
      humidity (RH) levels from 11% to 96% at 55 degrees C. Following a 24-h incubation
      under these stressed conditions, the solubility of DNA in different aqueous
      solutions and the water uptake of DNA were determined. The effects of solution pH
      and NaCl concentration and the presence of excipients (dextran and sucrose) on
      the subsequent moisture-induced aggregation of DNA were examined. The extent of
      this aggregation was compared with that of a supercoiled plasmid DNA. RESULTS:
      Upon a 24-h incubation at 55 degrees C, calf thymus DNA underwent a major
      moisture-induced aggregation reaching a maximum at a 60% RH; in contrast, the
      single-stranded DNA exhibited the maximal aggregation at a 96% RH. Moisture
      uptake and aqueous solubility studies revealed that the aggregation was primarily
      due to formation of inter-strand hydrogen bonds. Aggregation of DNA also
      proceeded at 37 degrees C, albeit at a slower rate. Solution pH and NaCl
      concentration affected DNA aggregation only at higher RH levels. This aggregation
      was markedly reduced by co-lyophilization with dextran or sucrose (but not with
      PEG). The aggregation pattern of a supercoiled plasmid DNA was similar to that of
      its linear calf thymus counterpart. CONCLUSIONS: The moisture-induced aggregation
      of lyophilized DNA is caused mainly by non-covalent cross-links between
      disordered, single-stranded regions of DNA. At high RH levels, renaturation and
      aggregation of DNA compete with each other. The aggregation is minimized at low
      RH levels, at optimal solution pH and salt concentration prior to lyophilization,
      and by co-lyophilizing with excipients capable of forming multiple hydrogen
      bonds, e.g., dextran and sucrose.

PMID- 17041792
TI  - Pediatric CT scan usage in Japan: results of a hospital survey.
AB  - PURPOSE: The aim of this study was to examine the usage parameters of diagnostic
      computed tomography (CT) in children because of concerns of possible overuse in
      Japanese hospitals, including the "technical" CT exposure settings and the
      "clinical" grounds for CT requests. MATERIALS AND METHODS: We examined the
      methodology at the radiology department to reduce radiation exposure to children
      and performed a retrospective study on pediatric CT requests during a 1-year
      period at Nagasaki University Hospital. The parameters of diagnostic CT usage for
      minor head trauma and acute appendicitis were studied in detail. RESULTS: CT
      radiation dose settings are adjusted for children based on guidelines issued by
      the Japan Radiological Society, with few limitations. CT requests were made for
      62% of minor head trauma cases and 76% of cases clinically suspected to be acute
      appendicitis. These figures are considerably higher than those reported by
      studies in the United Kingdom, Canada, or the United States. No specific
      guidelines are advocated regarding CT usage for minor head trauma. The diagnosis
      of acute appendicitis in children is almost routinely referred for "confirmation"
      by CT. CONCLUSION: CT radiation risks to children at Japanese hospitals need to
      be considered more seriously. Physicians should be encouraged to follow
      diagnostic algorithms that help avoid unnecessary CT usage in children.

PMID- 17041793
TI  - Upper midbrain profile sign and cingulate sulcus sign: MRI findings on sagittal
      images in idiopathic normal-pressure hydrocephalus, Alzheimer's disease, and
      progressive supranuclear palsy.
AB  - PURPOSE: On magnetic resonance imaging (MRI) sagittal sections, we sometimes
      encounter abnormal aspects of the superior profile of the midbrain and the
      cingulate sulcus in patients with dementia. In this preliminary study, we refer
      to these findings as the "upper midbrain profile sign" and the "cingulate sulcus
      sign." We prospectively evaluated the usefulness of these signs for the diagnosis
      of idiopathic normal-pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and
      progressive supranuclear palsy (PSP). MATERIALS AND METHODS: We evaluated the
      upper midbrain profile sign and the cingulate sulcus sign on MRI sagittal images
      obtained from 21 people with headaches but no neurological deficit (controls), 10
      iNPH patients, 11 AD patients, and 5 PSP patients. The upper midbrain profile
      sign indicated a concave shape to the superior profile of the midbrain on mid
      sagittal images, and the cingulate sulcus sign indicated a narrow, tight aspect
      of the posterior part of the cingulate sulcus on paramedian-sagittal images.
      RESULTS: These signs were never seen in any images from the controls. The upper
      midbrain profile sign was seen in 7 of 10 patients with iNPH, 5 of 11 with AD,
      and 3 of 5 with PSP. The cingulate sulcus sign was seen in all 10 patients with
      iNPH but was never seen in any patient with AD or PSP. CONCLUSION: The upper
      midbrain profile sign could support a diagnosis of PSP but cannot discriminate
      among iNPH, AD, and PSP. In contrast, the cingulate sulcus sign has a very high
      sensitivity for iNPH and should facilitate the distinction of iNPH from other
      dementias. In the clinical setting, it is momentous to evaluate these signs
      easily by one simple MRI sequence.

PMID- 17041794
TI  - Heel spur radiotherapy and radiation carcinogenesis risk estimation.
AB  - PURPOSE: Radiotherapy is a nonsurgical alternative therapy of painful heel spur
      patients. Nonetheless, cancer induction is the most important somatic effect of
      ionizing radiation. This study was designed to evaluate the carcinogenesis risk
      factor in benign painful heel spur patients treated by radiotherapy. MATERIALS
      AND METHODS: Between 1974 and 1999, a total of 20 patients received mean 8.16 Gy
      total irradiation dose in two fractions. Thermoluminescent dosimeters (TLD(100))
      were placed on multiple phantom sites in vivo within the irradiated volume to
      verify irradiation accuracy and carcinogenesis risk factor calculation. The 20
      still-alive patients, who had a minimum 5-year and maximum 29-year follow-up
      (mean 11.9 years), have been evaluated by carcinogenic radiation risk factor on
      the basis of tissue weighting factors as defined by the International Commission
      on Radiological Protection Publication 60. RESULTS: Reasonable pain relief has
      been obtained in all 20 patients. The calculated mean carcinogenesis risk factor
      is 1.3% for radiation portals in the whole group, and no secondary cancer has
      been clinically observed. CONCLUSION: Radiotherapy is an effective treatment
      modality for relieving pain in calcaneal spur patients. The estimated secondary
      cancer risk factor for irradiation of this benign lesion is not as high as was
      feared.

PMID- 17041795
TI  - Usefulness of intravascular ultrasonography for treatment of a ruptured vertebral
      dissecting aneurysm.
AB  - We report successful stent implantation and secondary coil embolization in a wide
      necked dissecting aneurysm in the vertebral artery. Intravascular ultrasonography
      (IVUS) showed the thrombosed pseudolumen clearly and enabled precise
      determination of the appropriate stent size. After stent implantation, Guglielmi
      detachable coil embolization was performed. Further experience is necessary to
      refine the technique, but IVUS may be useful to improve the safety of stent
      assisted embolization.

PMID- 17041796
TI  - Significance of preoperative lymphoscintigraphy and thin-slice computed
      tomography on sentinel node assessment: metastatic sentinel node in a lateral
      paramammary lesion out of axillary nodes from breast cancer.
AB  - Sentinel node status was evaluated using preoperative lymphoscintigraphy in a 43
      year-old woman who presented with an invasive ductal carcinoma in the lower outer
      quadrant of the right breast. Two strong hot nodules were visualized in the
      affected axillary basin on an early image, and a faint accumulation of
      radioactive tracer was lying between the cancer in the right lower outer quadrant
      and the axillary hot nodules on the lymphoscintigram taken at 90 min. The faint
      accumulation was considered to represent a small paramammary node on thin-slice
      computed tomography (CT) and was confirmed by node biopsy to be a sentinel node
      grossly involved with tumor cells. Immediate axillary dissection and adjuvant
      chemotherapy was subsequently performed. Careful evaluation using
      lymphoscintigraphy and thin-slice CT may be associated with increased
      localization of true sentinel nodes.

PMID- 17041797
TI  - Autoimmune pancreatitis with multifocal mass lesions.
AB  - Autoimmune pancreatitis (AIP) is radiologically characterized as diffuse swelling
      of the pancreatic parenchyma and irregular narrowing of the pancreatic ducts. We
      present a case of AIP with multiple small nodular lesions in the pancreas. This
      case suggests that AIP with only small nodular or localized lesions is more
      difficult to differentiate from pancreatic cancer than typical cases of AIP.

PMID- 17041798
TI  - Sertoli-stromal cell tumor of the right ovary: radiological-pathological
      correlation.
AB  - A case of Sertoli-stromal cell tumor of the right ovary is reported. The patient
      was a 50-year-old perimenopausal woman with abdominal distention due to a large
      pelvic tumor. She had no signs of androgen excess. A large solid sponge-like
      tumor with multicystic areas throughout, in which there were some small
      hemorrhagic spots, was shown on magnetic resonance (MR) imaging. No endometrial
      thickening of the uterus was seen. Pathology examination revealed a Sertoli
      stromal cell tumor with intermediate-to-poor differentiation. The edematous,
      watery, sponge-like appearance on the MR images correlated with the pathological
      findings.

PMID- 17041799
TI  - New ambulatory implant technique of high-dose-rate interstitial brachytherapy for
      prostate cancer.
AB  - PURPOSE: The aim of this study was to improve the performance status of prostate
      cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To
      this end, we have developed a new ambulatory implant technique. MATERIALS AND
      METHODS: Ten prostate cancer patients were treated with HDR-ISBT as monotherapy
      from October 2003 until March 2004. We utilized a new removable template, a
      flexible applicator with a nonmetallic bead and button stopper, and an inner
      catheter connecting the applicator and the transfer tube of the brachytherapy
      unit. We shortened the connector end of the flexible applicator to enable the
      patient to sit down and walk freely during the treatment time. RESULTS: All 10
      patients could walk without any support. No problem in the application was
      observed. CONCLUSION: Our new ambulatory implant technique for HDR-ISBT was able
      to improve the performance status of prostate cancer patients.

PMID- 17041800
TI  - Bezier surface reformation: an original visualization technique of cervical nerve
      roots on myelographic CT.
AB  - PURPOSE: The aim of this study was to assess the feasibility of an original
      reformation method of cervical myelographic computed tomography (CT) using the
      Bezier surface technique. MATERIAL AND METHODS: Presurgical myelographic computed
      tomography (CT) scans using a multidetector row CT scanner were performed in 25
      patients with avulsion injury of the cervical nerve roots. Each volumetric data
      set was reformatted using Bezier surface technique to depict the individual nerve
      root in a single image. In the reformatted images, visualization of the dorsal
      and ventral nerve roots between C4 and T1 on the uninjured side (300 nerves) was
      rated. RESULTS: Bezier surface reformation (BSR) images depicted the dorsal and
      the ventral nerve roots between C4 and C8 in 125 (100%) and 125 (100%) of 125
      nerves, respectively. The dorsal and the ventral nerve roots of T1 were depicted
      in 25 (100%) and 22 (88%) in 25 nerves, respectively. CONCLUSION: The BSR
      technique of cervical myelographic CT enables simultaneous display of multiple
      cervical nerve roots in one image. BSR is a feasible technique for the assessment
      of the cervical nerve roots.

PMID- 17041801
TI  - [Clinical drug therapy].

PMID- 17041802
TI  - Current developments in anti-platelet therapy.
AB  - Platelets play a life-saving role in hemostasis and blood clotting at sites of
      vascular injury and consequently are similarly involved in the pathological
      counterpart, namely thrombosis. Thus, anti-platelet therapy has become a mainstay
      in treatment and/or prophylaxis of conditions like myocardial infarction, stroke
      and other cardiovascular diseases. Acetyl-salicylic acid (ASA, aspirin) is still
      the most widely used agent and considered as the prototype antiplatelet drug.
      Since platelet activation occurs via several pathways that are not influenced by
      ASA, several other compounds have been developed to add to its beneficial effect.
      Currently four main classes of antiplatelet agents are available for clinical
      use: acetyl-salicylic acid (ASA), phosphodiesterase (PDE) inhibitors,
      thienopyridines and the intravenous GPIIb/IIIa antagonists. This article gives a
      concise review of these four classes of anti-platelet agents, using ASA as the
      reference standard.

PMID- 17041804
TI  - [Malign and refractory hypertension].
AB  - Early occurences of organ damage, mainly in the cardiovascular system, the
      central nervous system, of the kidney or the retina, are hallmarks of a malign
      course in arterial hypertension. Peracute hypertensive emergencies can lead to a
      rapid deterioration of organ functions, a slower development is observed in
      patients with therapy-resistant forms of arterial hypertension. In the following
      article we discuss the historical trends in terminology and epidemiology,
      clinical symptoms, and possible causes for therapy-resistant hypertension. The
      latter mainly focuses on possible secondary forms of hypertension and on thoughts
      on therapy-resistance in primary, idiopathic arterial hypertension, as well as on
      possible therapeutic approaches.

PMID- 17041803
TI  - [Oligonucleotide therapeutics - an emerging novel class of compounds].
AB  - Oligonucleotide therapeutics are short, single- or double-stranded DNA or RNA
      molecules consisting of strands of 10-50 nucleotides. By targeted modulation of
      gene expression oligonucleotides provide the chance of targeting diseases at
      their molecular level. Within this novel emerging class of compounds
      oligonucleotide therapeutics are discriminated by their structure, function and
      mode of action. While antisense oligonucleotides, ribozymes and siRNAs suppress
      the expression of a protein by complementary hybridizing with their target mRNA,
      aptamers bind like antibodies to their target protein and thereby inhibit its
      function. Immunostimulatory oligonucleotides are due to sequence motifs within
      their nucleotide sequence able to trigger a therapeutic exploitable immune
      response. Currently, there are only two oligonucleotide therapeutics approved by
      the FDA, namely the antisense oligonucleotide Fomivirsen and the aptamer Macugen.
      In this review the mode of action of the diverse oligonucleotide therapeutics and
      their current status in clinical development will be discussed.

PMID- 17041805
TI  - ["Me-too drugs" and the concept of a class effect].
AB  - A distinction between "Breakthrough-drug" and "Me-too-drug" within one
      therapeutic class of medication is usually not clinically relevant. The concept
      of a class effect, which would mean, that one "Me-too drug" could be substituted
      with another one from the same therapeutic class, is only proven for very few
      drug classes. Usually an individual risk/benefit assessment has to be performed
      for each specific drug. Even if a class effect has been established, doctors
      should not be forced to switch their patients to the cheapest drug within the
      same class. Patient specific factors such as compliance have to be considered
      first. However at the onset of a new therapy regimen, the drug with the lowest
      price should be used.

PMID- 17041806
TI  - [Sex-specific antihypertensive drug therapy].
AB  - BACKGROUND: Hypertension is a leading cause of cardiovascular diseases. To
      evaluate sex-specific differences in the prescription pattern of antihypertensive
      therapy, registry data from the regional health insurance fund "Burgenlandische
      Gebietskrankenkasse" (BGKK) were analyzed. MATERIAL AND METHODS: In a
      retrospective cross sectional cohort study data from 41499 individuals covered by
      the BGKK in 2003, and who had been treated with cardiovascular drugs were
      analyzed. Data were evaluated according to drug classifications. RESULTS: Among
      subjects treated with cardiovascular medication 38.3 % were males and 61.7 %
      females. The drug classes acting on the renin-angiotensin-system were prescribed
      more frequently than beta-blockers, calcium channel blockers, diuretics and
      antihypertensives. Women were treated more often with diuretics and beta
      blockers, whereas men received more antihypertensives and drugs acting on the
      renin angiotensin system (p < 0.01 between groups of sexes). CONCLUSION: Sex
      specific differences exist regarding the prevalence of antihypertensive drug
      prescriptions between men and women. Further, the prescription pattern of
      equivalently effective medications differs between sexes.

PMID- 17041807
TI  - Topical drug therapy in glaucoma.
AB  - Glaucoma is defined as a progressive optic neuropathy involving characteristic
      structural changes in the optic nerve head and corresponding visual field
      defects. Elevated intraocular pressure (IOP) is a major risk and causative factor
      for glaucomatous optic neuropathy. Although mechanisms other than elevated IOP
      may contribute to the underlying pathophysiology of glaucoma, reducing IOP
      remains the primary goal of therapy. Recent clinical studies have shown that
      decreasing the IOP can delay, or in some cases prevent progression of this
      chronic ocular disease. Over the past decade, several new medical therapies have
      become available for the treatment of glaucoma. In this article a review of
      topical glaucoma therapy is presented.

PMID- 17041808
TI  - [Cytochrom-P450 mediated drug interactions caused by antibiotics].
AB  - This review focuses on drug interactions with commonly prescribed antibiotics.
      With each drug coadministered, the likelihood of an adverse interaction increases
      exponentially. Thus, poly-pharmacotherapy possesses important clinical challenges
      for clinicians and exposes patients to potentially life-threatening risks. In
      particular, following co-administration of drugs such as tricyclic
      antidepressants, anticoagulants and antiarrhythmics, which are characterized by
      narrow therapeutic windows, even small changes in plasma levels can cause serious
      adverse reactions and/or therapeutic failure. The hepatic and intestinal
      cytochrome, or CYP-450 enzyme system is responsible for the biotransformation of
      a multitude of drugs and is frequently involved in drug interactions. The present
      review therefore presents a comprehensive overview on potential drug interactions
      with antibiotics, which are mediated by the cytochrome-P450-enzymes.

PMID- 17041809
TI  - The metabolic effects of long term exercise in Type 2 Diabetes patients.
AB  - INTRODUCTION: The effectiveness of physical exercise in the management of
      diabetes mellitus type 2 is well established. The purpose of this investigation
      was to evaluate the effect of long term exercise on glycemic and metabolic
      control measured after eight months in contrast to patients who had ceased their
      training after four months. METHODS: After an effective 4 months' strength
      training or endurance training period, ten patients (5 male and 5 female, mean
      age +/- SE:57.1 +/- 1.6 yr) were randomised to a further 4 months of combined
      endurance and strength training, while a control group of 10 patients (5 male and
      5 female, mean age +/- SE:56.9 +/- 1.6 yr) ceased training. RESULTS: Long term
      glycemic control improved and HbA1C values fell from 6.9 +/- 0.4 to 6.2 +/- 0.2
      in active patients and increased from 7.5 +/- 0.4 to 8.7 +/- 0.6 in control
      patients (p = 0.002). Baseline levels of total cholesterol significantly
      decreased in training group (205.5 mg/dl +/- 14.1 to 177.5 +/- 13.3) and
      increased in controls (185.9 +/- 14.1 to 220.2 +/- 15.8) [p = 004]. In addition,
      significant decreases in LDL-cholesterol and triglyceride levels (both p < 05)
      were observed in the training group compared to controls. CONCLUSION: This study
      showed that in addition to a 4 month training period, continuation of training
      proved highly beneficial with further reductions in fasting blood glucose, HbA1C,
      total cholesterol, LDL-cholesterol, triglyceride, and an elevation in HDL
      cholesterol concentrations in diabetes mellitus type 2 patients, thus resulting
      in a reduced atherogenic lipid profile. In contrast, patients who ceased training
      after 4 months developed an atherogenic lipid profile and a worsened glycemic
      control. The results of this study indicate that long term exercise plays an
      important role in the treatment of diabetes mellitus type 2 and may protect
      against the development of cardiovascular diseases.

PMID- 17041810
TI  - Transcriptional control in the mammalian liver: liver development, perinatal
      repression, and zonal gene regulation.
AB  - Liver function is crucial for maintaining metabolic homeostasis in mammals.
      Numerous genes must be properly regulated for the liver to develop and perform a
      variety of activities. Several recent gene-knockout studies in mice have
      clarified the roles of GATA6, HNF4alpha, and Foxa1/Foxa2 in early stages of liver
      formation. After the liver forms, transcriptional changes continue to occur;
      during the perinatal period, certain genes such as alpha-fetoprotein and H19 are
      silenced, others are activated, and position-dependent (or zonal) regulation is
      established. Zhx2 was recently identified as one factor involved in postnatal
      repression of alpha-fetoprotein and other genes. Furthermore, several studies
      indicate that negative regulation is involved in the zonal control of glutamine
      synthetase. Finally, exciting new evidence indicates that signaling through the
      Wnt/beta-catenin pathway is also involved in zonal regulation in the adult liver.

PMID- 17041811
TI  - Huntington's disease: from huntingtin function and dysfunction to therapeutic
      strategies.
AB  - Huntington's disease (HD) is a neurodegenerative disorder that usually starts in
      middle age and is characterized by involuntary movements (chorea), personality
      changes and dementia, leading to death within 10-20 years. The defective gene in
      HD contains a trinucleotide CAG repeat expansion within its coding region that
      expresses a polyglutamine repeat in the protein huntingtin. Together with the
      characteristic formation of aggregates in HD, aberrant protein interactions and
      several post-translational modifications affect huntingtin during disease
      progression and lead to the dysfunction and death of selective neurons in the
      brains of patients. The exact molecular mechanisms by which mutant huntingtin
      induces cell death are not completely understood but may involve the gain of new
      toxic functions and the loss of the beneficial properties of huntingtin. This
      review focuses on the cellular functions in which huntingtin is involved and how
      a better understanding of pathogenic pathways can lead to new therapeutic
      approaches.

PMID- 17041812
TI  - Structural biology of protein tyrosine kinases.
AB  - Our current understanding of the structure, mechanism of action and modes of
      regulation of the protein tyrosine kinase family owes a great deal to structural
      biology. Structures are now available for more than 20 different tyrosine kinase
      domains, many of these in multiple conformational states. They form the basis for
      the design of experiments to further investigate the role of different structural
      elements in the normal function and regulation of the protein and in the
      pathogenesis of many human diseases. Once thought to be too similar to be
      specifically inhibited by a small molecule, structural differences between
      kinases allow the design of compounds which inhibit only an acceptable few. This
      review gives a general overview of protein tyrosine kinase structural biology,
      including a discussion of the strengths and limitations of the investigative
      methods involved.

PMID- 17041813
TI  - Does composition medium affect the psychometric properties of scores on an
      exercise designed to assess written medical communication skills?
AB  - The ECFMG Clinical Skills Assessment (CSA) was developed to evaluate whether
      graduates of international medical schools are ready to enter graduate training
      programs in the United States. The performance-based patient note exercise is
      specifically used to assess an examinee's ability to summarize, synthesize and
      interpret the data collected in a patient interview. The purpose of this study
      was to investigate whether choice of composition method (typing or writing)
      affected the psychometric properties of the scores. Using data for a 1-year
      period, the validity and reliability of typed and written notes was contrasted.
      Although the characteristics of individuals who chose whether or not to type were
      different, the statistical analyses indicated that, controlling for examinee
      ability, physician examiner ratings of the written summaries were not influenced
      by composition method. The results of this study suggest that the psychometric
      properties of the patient note scores are invariant with respect to composition
      method.

PMID- 17041814
TI  - Medical students' attitudes toward underserved patients: a longitudinal
      comparison of problem-based and traditional medical curricula.
AB  - Medical education has been shown to negatively influence student attitudes toward
      certain types of patient populations. Past research does not inform current
      educational practice because today's medical school environment is different from
      when most of the published research was conducted. There are more female
      students, curricular innovations such as problem-based learning have changed the
      framework for educational delivery, and longitudinal studies, which could inform
      when interventions may be needed, are uncommon. The purposes of this
      longitudinal, prospective cohort study were to compare the attitudes of Problem
      based learning and Traditional curriculum students toward providing care for
      medically indigent patients as they progressed through the four-year
      undergraduate medical education curriculum, and to determine if gender
      differences were apparent and persisted over time. Attitudes of one cohort of
      students enrolled in separate curricula were studied. The outcome measure was the
      Medical Student Attitudes Toward the Underserved questionnaire, which was
      administered three times. A linear mixed effects regression analysis was
      performed to examine changes in factor scores over time and whether these changes
      differed between Problem-based and Traditional students, and males and females.
      Longitudinal findings revealed that commitment to caring for the medically
      underserved was greater when students entered medical school than when they
      graduated. Students in both curricula, as well as male and female students,
      experienced increasingly negative attitudes over the four year period. Decline in
      attitudes toward medically underserved patients was similar to previous research
      results. This study showed that attitudes of students were not influenced by the
      preclinical curriculum they experienced.

PMID- 17041815
TI  - Treatment innovation in behavioral rehabilitation of stroke: Removing limits on
      recovery.

PMID- 17041816
TI  - Clinical and cognitive predictors of swallowing recovery in stroke.
AB  - This retrospective study determined whether specific neurological features were
      associated with initial and final swallowing outcomes in acute stroke patients. A
      chart review of 65 acute stroke patients suggested that certain clinical and
      neurocognitive behaviors were associated with swallowing outcomes. Hemispatial
      neglect was significantly associated with initial nonoral dietary intake, whereas
      aphasia was not associated with swallowing outcome. Results from the initial
      clinical swallowing evaluations suggested that the presence of at least four of
      six clinical features (cough after swallow, voice change after swallow, abnormal
      volitional cough, abnormal gag reflex, dysphonia, and dysarthria) were associated
      with poor initial and final swallowing outcomes. Whether specific lesion
      location, size, or a combination of clinical neurological deficits are associated
      with poor initial and final swallowing outcomes is unclear. Prospective studies
      are warranted for further investigation of these relationships.

PMID- 17041817
TI  - Does motor lateralization have implications for stroke rehabilitation?
AB  - Recent findings on motor lateralization have revealed consistent differences in
      the control strategies of the dominant and nondominant hemisphere/limb systems
      that could have implications for hemiplegic stroke patients. Studies in stroke
      patients have demonstrated deficiencies in the ipsilesional arm that reflect
      these distinctions; patients with right-hemisphere damage tend to show deficits
      in positional accuracy, and patients with left-hemisphere damage show deficits in
      trajectory control. Such deficits have been shown to impede functional
      performance; yet patients with severe dominant-side hemiplegia must often use the
      nondominant arm as the primary manipulator for activities of daily living.
      Nevertheless, the nondominant arm may not spontaneously become efficient as a
      dominant manipulator, as indicated by the persistence of deficits in chronic
      stroke patients. More research is necessary to determine whether motor therapy
      can facilitate a more effective transition of this arm from a nondominant to a
      dominant controller.

PMID- 17041818
TI  - Treatability of different components of aphasia - insights from a case study.
AB  - In this phase I clinical rehabilitation study, we investigated the effects of
      phonological rehabilitation for alexia and aphasia in an individual 54 years
      after a left-hemisphere ischemic infarction. In the context of a single-subject
      design, we studied whether treatment would improve phonological processing,
      reading, and generalization to untreated behaviors. While results showed a lack
      of generalization to real-word reading aloud, improvement was present in
      phonological processing, language function (Western Aphasia Battery Aphasia
      Quotient, Boston Naming Test, Reading Comprehension Battery for Aphasia), and
      auditory processing (Revised Token Test). Improvement in the lexical-semantic
      system was attributed to informal forced-use language treatment. We concluded
      that phonological therapies are unlikely to be successful unless a minimum
      initial level of phonological sequence knowledge exists; therapies that pressure
      subjects to use verbal communication can achieve clinically important gains in
      communicative ability that generalize to untreated behaviors. This study also
      demonstrates the importance of a careful analysis of the patient's language
      ability before a therapeutic strategy is chosen.

PMID- 17041819
TI  - Monocular patching in subjects with right-hemisphere stroke affects perceptual
      attentional bias.
AB  - Monocular patching is a possible inexpensive treatment for spatial neglect.
      Previous studies were unpromising, but since neglect symptoms are heterogeneous,
      fractionating spatial bias may detect significant effects of patching.
      Poststroke, perceptual-attentional (PA) spatial bias, motor-intentional (MI)
      spatial bias, or both may occur. In this study, six poststroke subjects bisected
      lines while self-monitoring their performance via a camera/video apparatus. We
      dissociated PA and MI spatial bias by right-left reversing visual feedback in
      some trials. Subjects were tested with and without right and left eye patches.
      Patching did not affect group line-bisection error, but both right and left
      patches decreased individual subject PA spatial bias (p < 0.05). We detected no
      patching effect on individual subject MI spatial bias (significant patch side by
      bias interaction, p = 0.03). When we examined each subject's results separately,
      patching improved performance in subjects who had greater PA and MI spatial
      biases. We conclude that monocular patching may primarily affect poststroke PA
      spatial bias. Further studies on this intervention are needed.

PMID- 17041820
TI  - Dysphagia in stroke: Development of a standard method to examine swallowing
      recovery.
AB  - This study began development of a standard method that uses the videofluoroscopic
      swallow study for evaluation of swallowing recovery after stroke based on a
      definition of dysphagia derived from three domains: bolus timing, bolus
      direction, and bolus clearance. Two experiments were conducted: one that defined
      normal versus disordered swallowing based on the range of scores in a sample of
      healthy adults (n = 13), and one that applied these thresholds to nine stroke
      patients to identify the presence of dysphagia. Results indicate that acute and
      protracted dysphagia may be more accurately detected by identifying abnormalities
      on multiple objective measures of swallowing rather than on laryngeal penetration
      or aspiration alone. Results indicate that our selected measures and use of
      healthy control subjects to establish normal thresholds may eventually contribute
      to the definition and differentiation of dysphagic and nondysphagic patients.
      Further research with a broader sample of healthy controls and stroke patients is
      mandatory.

PMID- 17041821
TI  - Animal-assisted therapy for persons with aphasia: A pilot study.
AB  - This study explored the effects and effectiveness of animal-assisted therapy
      (AAT) for persons with aphasia. Three men with aphasia from left-hemisphere
      strokes participated in this study. The men received one semester of traditional
      therapy followed by one semester of AAT. While both therapies were effective, in
      that each participant met his goals, no significant differences existed between
      test results following traditional speech-language therapy versus AAT. Results of
      a client-satisfaction questionnaire, however, indicated that each of the
      participants was more motivated, enjoyed the therapy sessions more, and felt that
      the atmosphere of the sessions was lighter and less stressed during AAT compared
      with traditional therapy.

PMID- 17041822
TI  - Word-retrieval treatment in aphasia: Effects of sentence context.
AB  - Word-retrieval treatment studies in aphasia have reported the greatest influences
      on picture naming for trained words. To increase treatment effects to untrained
      words and sentence contexts, we investigated a sentence-reading treatment
      hierarchy that moves from errorless to generative production of sentences
      incorporating target nouns and verbs. In an individual with nonfluent aphasia,
      treatment resulted in improved picture naming for nouns and verbs and generalized
      increases in numbers of grammatical sentences and content words following noun
      therapy. A second individual with fluent aphasia improved little in picture
      naming and sentence-generation tasks for both nouns and verbs. This sentence
      based word-retrieval training, in which semantic and syntactic processes are
      engaged, led to improvements in word-retrieval measures during spontaneous
      sentence generation, but only for the participant with nonfluent aphasia.
      Contrary to expectations, these changes were greater following noun therapy than
      they were following verb therapy.

PMID- 17041823
TI  - Effects of two treatments for aprosodia secondary to acquired brain injury.
AB  - Expressive aprosodia is an impaired ability to change one's voice to express
      common emotions such as joy, anger, and sadness. Individuals with aprosodia speak
      in a flat, unemotional voice that often results in miscommunicated emotional
      messages. This study investigated two conceptually based treatments for
      expressive aprosodia: imitative treatment and cognitive-linguistic treatment.
      Five women and nine men with expressive aprosodia following right-hemisphere
      brain damage received the treatments in two phases 1 month apart in random order.
      Treatment was received 3 to 4 days a week for a total of 20 sessions each phase.
      As the outcome measure, sentences that elicited treated (happy, angry, sad,
      neutral) and untreated (fear) emotional tones of voice were administered during
      baseline, prior to treatment sessions, following treatment termination, and at 1-
      and 3-month follow-ups. Effect sizes indicated that treatment effects were modest
      to substantial and that 12 participants responded to at least one treatment. Four
      responsive participants who were available for follow-up showed benefit at 1 and
      3 months posttreatment. Most visual and statistical analyses were congruent.

PMID- 17041824
TI  - A telerehabilitation approach to delivery of constraint-induced movement therapy.
AB  - We have developed a device called AutoCITE (Automated Constraint-Induced Therapy
      Extension) that automates the intensive training component of constraint-induced
      (CI) movement therapy, also known as CI therapy. This study evaluated the
      effectiveness of AutoCITE training in a telerehabilitation setting when
      supervised remotely and with only intermittent interaction with a therapist.
      Seven participants with chronic stroke trained with AutoCITE for 3 h/d for 10
      consecutive weekdays. The therapist supervised the training from a different room
      in the clinic using remote control of the AutoCITE computer and teleconferencing
      equipment when needed. Treatment gains on the Motor Activity Log were quite large
      (p < 0.001, d' = 3), while gains on the Wolf Motor Function Test and the Jebsen
      Taylor Hand Function Test were large (p < 0.05, d' > 0.9). Gains were comparable
      in size with those previously reported for participants who received equal
      intensities of directly supervised AutoCITE training or standard one-on-one CI
      therapy without the device.

PMID- 17041825
TI  - Relationships between upper-limb functional limitation and self-reported
      disability 3 months after stroke.
AB  - This study explored relationships between upper-limb (UL) functional limitations
      and self-reported disability in stroke patients with relatively pure motor
      hemiparesis who were enrolled in an acute rehabilitation treatment trial. All
      participants were enrolled in the VECTORS (Very Early Constraint Treatment for
      Recovery from Stroke) study. VECTORS is a single-center pilot clinical trial of
      early application of constraint-induced movement therapy (CIMT). All 39 subjects
      who completed 90 days of VECTORS were included in this analysis. Trained study
      personnel who were blinded to the treatment type performed all evaluations. Data
      in this article examine relationships between assessments performed 90 days after
      stroke. Functional limitation measures included the Action Research Arm (ARA)
      test and Wolf Motor Function Test (WMFT), and self-reported disability measures
      included the Functional Independence Measure (FIM) and Motor Activity Log (MAL)
      (by telephone). Mean plus or minus standard deviation time from stroke onset to
      randomization was 9.4 plus or minus 4.3 days, and median time to follow-up was 99
      days (range 68-178). Subjects with perfect or near-perfect scores on the ARA test
      or WMFT reported residual disability on the FIM and MAL. Quality of movement on
      the WMFT (functional ability score) was not strongly associated with self
      reported frequency, and speed of movement on the WMFT (timed score) was not
      associated with self-reported frequency (MAL amount of use). In this early UL
      intervention trial, we found that perceived disability measures captured
      information that was not assessed by functional limitation and impairment scales.
      Our results indicate that excellent motor recovery as measured by functional
      limitation and impairment scales did not equal restoration of everyday productive
      UL use and speed of task completion did not translate to actual use. Our results
      confirm the need for a measurement strategy that is sensitive to change, assesses
      a broad performance range, and detects meaningful clinical improvements in early
      rehabilitation intervention trials.

PMID- 17041826
TI  - Influence of intensive phonomotor rehabilitation on apraxia of speech.
AB  - In this phase I rehabilitation study, we investigated the effects of an intensive
      phonomotor rehabilitation program on verbal production in a 73-year-old male, 11
      years postonset a left-hemisphere stroke, who exhibited apraxia of speech and
      aphasia. In the context of a single-subject design, we studied whether treatment
      would improve phoneme production and generalize to repetition of multisyllabic
      words, words of increasing length, discourse, and measures of self-report. We
      predicted that a predominant motor impairment would respond to intensive
      phonomotor rehabilitation. While able to learn to produce individual sounds, the
      subject did not exhibit generalization to other aspects of motor production.
      Discourse production was judged perceptually slower in rate and less effortful,
      but also less natural. Finally, self-report indicated less apprehension toward
      speaking with unfamiliar people, increased telephone use, and increased ease of
      communication.

PMID- 17041827
TI  - Using the magnetic resonance three-dimensional volume rendering for tissues
      technique in the planning of craniotomy flaps with linear scalp incision.
AB  - Preoperative three-dimensional images with surface venous anatomy may be used in
      the planning of a linear scalp incision and the opening site of the dura mater
      for protection of surface veins during surgical dissection, and to find the
      splitting site of the brain according to the lesion. In 45 patients who had a
      brain tumor, linear scalp incision planning was done by regarding the three
      dimensional images derived from post-contrast time-of-flight (TOF) sequence raw
      data. The findings of correspondence and the quality of routine contrast-enhanced
      magnetic resonance imaging (MRI) and three-dimensional volume rendering for
      tissues (VRT) images were analyzed separately with the surgical findings
      according to a visual grading system. Our experience revealed that the surgical
      findings correlated well with the three-dimensional VRT images. According to a
      visual surgical grading system, a grade III correlation was found in 20 (45%),
      grade II in 15 (33%), grade I in 7 (15%), and grade 0 in 3 (7%) patients in our
      study population. At the end of our research we conclude that this method is
      useful in terms of the preoperative determination of brain surface anatomy and
      may be used in the determination of the site of a linear scalp incision according
      to the localization of an intracranial lesion.

PMID- 17041828
TI  - Endoscopic management of thalamic gliomas.
AB  - The management of thalamic gliomas is extremely variable, ranging from radical
      excision in some cases to more conservative therapy such as a biopsy and
      radiation. There is a high incidence of associated hydrocephalus. The principles
      of management are, therefore, histological diagnosis, CSF diversion and adjuvant
      therapy. Endoscopy appears to offer a new approach to achieve histology and CSF
      diversion. The various goals achieved with the use of endoscopy in the management
      of 4 patients with thalamic gliomas are described. With the endoscope we achieved
      histological diagnoses and CSF diversion was facilitated in all these cases.
      There were no complications. The advantages of endoscopy in the management of
      thalamic masses are discussed. Endoscopic intervention appears to offer a modular
      approach to these lesions.

PMID- 17041829
TI  - Application of intraoperative 3D ultrasound during navigated tumor resection.
AB  - Intraoperative 3D ultrasound (3D-iUS) may enhance the quality of neuronavigation
      by adding information about brain shift and tumor remnants. The aim of our study
      was to prove the concept of 3D ultrasound on the basis of technical and human
      effects. A 3D-ultrasound navigation system consisting of a standard personal
      computer containing a video grabber card in combination with an optical tracking
      system (NDI Polaris) and a standard ultrasound device (Siemens Omnia) with a 7.5
      MHz probe was used. 3D-iUS datasets were acquired after craniotomy, at different
      subsequent times of the procedure and overlaid with preoperative MRI. All
      patients underwent early postoperative 3D MRI including contrast agent within 24
      hours after surgery. Acquisition of 3D iUS and the fusion with preoperative MRI
      was successful in 22/23 patients. The expenditure of time was at least 5 minutes
      for one intraoperative 3D US dataset. The technique was used three to seven times
      during surgery. The quality of the ultrasound images was superior in cases of
      metastasis, meningeoma and angioma over those in malignant glioma. Brain shifting
      ranged from 2-25 mm depending on localization and kind of tumor. A resection
      control was possible in 78%. All six neurosurgeons demonstrated a learning curve.
      The introduction of 3D ultrasound has increased the value of neuronavigation
      substantially, making it possible to update several times during surgery and
      minimize the problem of brain shift. Configuration of both the 3D iUS based on a
      standard ultrasound system and the MR navigation system is time- and especially
      cost-effective. Faster navigational datasets and more intuitive image-guided
      surgery enable novel and user-friendly display techniques.

PMID- 17041830
TI  - The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple
      or large-size tumors.
AB  - OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy
      using the Cyberknife are useful treatments for multiple or large metastases. Here
      we present our results of Cyberknife radiosurgery for 71 patients with 148
      metastatic brain lesions. METHODS: There were 32 women and 39 men with a median
      age of 63 (range: 30-88) years. Radiographic follow-up was available for 60
      patients with 104 lesions. The mean and median initial volumes of the tumor per
      lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time
      of the initial Cyberknife treatment. Forty patients (56%) had a single lesion,
      and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number
      of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a
      fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy
      (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up,
      there were no permanent symptoms resulting from radiation necrosis. Overall 6
      month and 1-year survival rates were 74% and 47%, respectively, and the median
      survival time was 56 weeks. The Karnofsky performance score and extracranial
      metastasis were significant prognostic factors at 6 months and 1 year,
      respectively, in both univariate and multivariate analyses. Age or multiple
      metastases did not influence prognosis at 6 months and 1 year. Local control was
      achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage,
      no patient died as a result of intracranial disease. Twenty-five patients
      developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4
      weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by
      salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of
      patients with large tumors, our results for survival and tumor control rates are
      comparable to those of published series. The Cyberknife provides the advantage of
      allowing for fractionated treatment to multiple or large-size tumors.

PMID- 17041831
TI  - Application of neuronavigation system to brain tumor surgery with clinical
      experience of 420 cases.
AB  - A new era of neurosurgery has recently been unveiled with the advent of image
      guided surgery. The use of neuronavigation is beginning to have a significant
      impact on a variety of intracranial procedures. Herein, we report our clinical
      experience using a neuronavigation system with different surgical applications
      and techniques for a variety of brain tumors. We used the BrainLab VectorVision
      neuronavigation system, which is a frameless and image-guided system. We operated
      on 420 cases having various types of brain tumor with the help of this system.
      The mean target localizing accuracy and mean volume were 1.15 mm and 30.8 mL (0.2
      216.4 mL), respectively. We utilized this system to effectively make bone flaps,
      to detect critically located, deep-seated, subcortical, skull-base and skull bone
      tumors, and to operate on intraparenchymal lesions with grossly unclear margins,
      such as gliomas. We also performed tumor biopsy using the combination of a
      conventional stereotactic biopsy instrument and an endoscope. The application of
      the neuronavigation system not only revealed benefits for operative planning,
      appreciation of anatomy, lesion location and the safety of surgery, but also
      greatly enhanced surgical confidence.

PMID- 17041832
TI  - Endoscopic carpal tunnel release in the elderly.
AB  - The present study is aimed to clarify the postoperative outcome of endoscopic
      carpal tunnel release in elderly patients with carpal tunnel syndrome. Endoscopic
      carpal tunnel release was performed on 37 hands of 27 patients (2 men, 25 women)
      who were aged 70 years or older and clinically and electrophysiologically
      diagnosed with carpal tunnel syndrome. Mean age at the time of surgery was 74.5
      years (range: 70-85 years). Mean postoperative follow-up was 35.5 months (range:
      12-114 months). Pain was present preoperatively in 20 hands, but quickly resolved
      postoperatively in all cases. Numbness completely disappeared in 13 of 37 hands
      (35.1%), but some degree of numbness remained in the remaining cases.
      Preoperative severity of thenar muscle atrophy was none in 4 hands, mild in 7
      hands, moderate in 12 hands and severe in 14 hands. Postoperative severity of
      thenar muscle atrophy at final follow-up was none in 13 hands, mild in 16 hands,
      moderate in 2 hands and severe in 6 hands, confirming that thenar muscle atrophy
      improves even in elderly patients. However, moderate or severe thenar muscle
      atrophy remained in 8 hands (21.6%). Endoscopic carpal tunnel release should be
      considered in the elderly, even though clinical symptoms may not improve
      substantially in advanced cases.

PMID- 17041833
TI  - Morphological study of the spinal canal content for subarachnoid endoscopy.
AB  - STUDY DESIGN AND OBJECTIVE: This study was designed to examine the morphology of
      the spinal dural sac and contents, using magnetic resonance imaging in order to
      define the inner geometrical dimensions that confine the manoeuvre of an
      endoscope inserted in the lumbar region and along the thoracic and cervical
      spine. BACKGROUND: The morphology of the spine has been studied since the
      development of myelography. However, most studies have measured the diameters of
      the spinal cord only, not the size of the subarachnoid space. In addition, the
      few studies available on the subarachnoid space have focused on the cervical
      spine, leaving a near-complete dearth of data on the subarachnoid space
      dimensions along the thoracic spine. METHODS: Based on MRI images of the spine
      from 42 patients, the dimensions of the spinal cord, dural sac, and subarachnoid
      space were measured at mid-vertebral and inter-vertebral disc levels. RESULTS: It
      was found that at each selected transverse level, the subarachnoid space tends to
      be symmetrical on the right and left sides of the cord, and measures 2.5 mm on
      average. However, the posterior and anterior segments, measured on the mid
      sagittal plane, are generally asymmetrical and vary widely in size, ranging from
      1 to 5 mm. These measurements match those found in previous studies, where these
      are available. The coefficient of variance for the dimensions of the subarachnoid
      space is as high as 42.4%, while that for the dimensions of the spinal cord is 10
      15%. CONCLUSIONS: The findings presented here expand our knowledge of the spinal
      canal's morphology, and show that an endoscope designed to travel within the
      subarachnoid space must be smaller than 2.5 mm in diameter.

PMID- 17041834
TI  - Open-window laparotomy during a transperitoneal approach to the lower lumbar
      vertebrae: new method for reducing complications.
AB  - There are numerous approaches for exploring the lower lumbar vertebrae, and the
      anterior transperitoneal route is one of the most popular. Like all surgical
      techniques, this approach has advantages and disadvantages. It provides direct
      access to the target tissue through a small incision, exposes the anterior
      portion of the vertebrae well, and permits good visualization of the major
      vessels, thus reducing risk of vascular injury and life-threatening hemorrhage.
      However, compared to the extraperitoneal route, the transperitoneal approach
      carries higher risks for peritoneal complications. This article describes a new
      practical method for creating an extraperitoneal passageway or "window" during
      transperitoneal approaches to the lower lumbar vertebrae. Isolation of the
      peritoneal cavity and its contents with this technique can reduce peri- and
      postoperative abdominal complications.

PMID- 17041835
TI  - Trigeminal neuroma with extracranial extension: the 31st case.
AB  - Neuromas arising from the distal branches of the trigeminal nerve with
      extracranial extension are unusual. Here, we present the clinical features,
      diagnosis and treatment of 28-year-old woman with trigeminal neuroma with
      extension to the infratemporal fossa.

PMID- 17041836
TI  - "Triple cross" of the hypoglossal nerve and its microsurgical impact to
      entrapment disorders.
AB  - OBJECTIVE: Cadaveric dissections were performed to review the intracranial and
      extracranial course of the hypoglossal nerve. The neurological significance of a
      newly defined "triple cross" of the hypoglossal nerve is discussed. MATERIALS AND
      METHODS: 10 cadaveric heads (left and right; 20 sides) were dissected using
      microsurgical techniques. RESULTS: In the cisternal segment of hypoglossal nerve,
      the diameter of the rostral trunk amounted to 155-680 microm (mean 435 microm),
      and the caudal trunk to 210-820 microm (mean 482 microm). The roots formed three
      trunks in 20% of the hypoglossal nerves and two trunks in the rest. As a first
      cross, the anterior medullary segment of the vertebral artery crossed the
      hypoglossal nerve roots in 14 of 20 sides (70%). As a rare variation, the
      vertebral artery extended medial to the nerve (25%) or between its roots (5%).
      The second cross was found between the descendens hypoglossus and the occipital
      artery (75%), sternocleidomastoid artery and vein complex (15%) and external
      carotid artery (10%). The third cross was shown in the submandibular triangle
      between the lingual hypoglossus and its drainage vein; vena committans nervus
      hypoglossus. CONCLUSION: Throughout its way, the hypoglossal nerve passes over
      vascular structures in three crossing points which may serve as a probable cause
      of hypoglossal nerve entrapment disorders.

PMID- 17041837
TI  - Outcome prediction of third ventriculostomy: a proposed hydrocephalus grading
      system.
AB  - An important factor in making a recommendation for different treatment modalities
      in hydrocephalus patients (VP shunt versus endoscopic third ventriculostomy) is
      the definition of the underlying pathology which determines the prognosis/outcome
      of the surgical procedure. Third ventriculostomies (3rd VS) are successful mainly
      in obstructive hydrocephalus but also in some subtypes of communicating
      hydrocephalus. A simple, easily applicable grading system that is designed to
      predict the outcome of 3rd VS is proposed. The hydrocephalus is graded on the
      basis of the extent of downward bulging of the floor of the third ventricle,
      which reflects the pressure gradient between the 3rd ventricle and the basal
      cisterns, presence of directly visualised CSF pathway obstruction in MRI, and the
      progression of the clinical symptoms resulting in five different grades. In this
      proposed grading system, grade 1 hydrocephalus subtype shows no downward bulged
      floor of the 3rd ventricle, no obstruction of the CSF pathway, and no progressive
      symptoms of hydrocephalus. There is no indication for 3rd VS. Grades 2 to 4 show
      different combinations of the described parameters. Grade 5 subtype shows a
      markedly downward bulged floor of the 3rd ventricle and direct detection of the
      CSF pathway obstruction (i.e., aqueductal stenosis) with progressive clinical
      deterioration. Retrospective application of this grading scheme to a series of 72
      3rd VS has demonstrated a high correlation with the outcome: The success rate in
      grade 3 reached 40%, in grade 4: 58%, and in grade 5: 95%. This standardised
      grading system predicts the outcome of 3rd VS and helps in decision making for
      3rd VS versus VP shunting.

PMID- 17041838
TI  - Endoscopic removal of ethmoido-sphenoidal foreign body with intracranial
      extension.
AB  - We describe the case of a foreign body lodged into ethmoidal labyrinth and
      sphenoidal sinus with fracture of the clivus and consequent rhinoliquorrhea
      removed by an endoscopic technique. We performed a skull base plasty to close the
      rhino-liquoral fistula with resolution of the rhinoliquorrhea. There were no
      postoperative complications and there was a good therapeutic result at long-term
      follow-up.

PMID- 17041839
TI  - Neuroendoscopic management of a solitary pineal region tumor. Case report of an
      adenocarcinoma metastasis.
AB  - The present case describes a two-step endoscopic management of hydrocephalus and
      diagnosis of a single pineal region metastasis arising from a gastric
      adenocarcinoma. A 62-year-old man presenting with signs of subacute obstructive
      hydrocephalus from a pineal region mass had at first been treated with an
      endoscopic third ventriculostomy. As cerebrospinal fluid tumor markers (alpha
      fetoprotein, beta-human chorionic gonadotropin) were negative, an endoscopic
      biopsy of the pineal region tumor was performed through a more anterior frontal
      burr hole. Pathology showed an adenocarcinoma and primary tumor work-up revealed
      an unsuspected gastric tumor, the pathology of which matched with the
      intracranial metastasis. The present report emphasizes the role of neuroendoscopy
      in pineal region tumors and reports a rare case of a solitary gastric
      adenocarcinoma metastasis in this location.

PMID- 17041840
TI  - Fatal intratumoral hemorrhage immediately after gamma knife radiosurgery for
      brain metastases: case report.
AB  - Radiosurgical treatment of brain tumors is sometimes considered to be free from
      significant acute complications or adverse effects. A rare case of fatal
      intratumoral hemorrhage immediately after gamma knife radiosurgery (GKR) for
      brain metastasis is reported. A 46-year-old woman with lung cancer complicated by
      systemic dissemination experienced an acute episode of headache, speech
      disturbances, and right-side hemiparesis. She had no history of arterial
      hypertension or coagulation disorders. CT and MRI disclosed multiple brain
      metastases. The largest tumor, which was located in the left frontal lobe and
      caused a significant mass effect, was removed microsurgically without any
      complications. GKR for nine residual metastases was done on the fourth
      postoperative day. The marginal dose, which corresponded to the 50% prescription
      isodose line, constituted 20 Gy. No complications were noticed during frame
      fixation, treatment itself, or frame removal. Fifteen minutes after the end of
      the GKR session the patient acutely fell into a deep coma. Urgent CT disclosed a
      massive hemorrhage in the left cerebellar hemisphere in the vicinity of the
      radiosurgically treated lesion. The patient died 4 days later and autopsy
      confirmed the presence of intratumoral hemorrhage. In conclusion, GKR for
      metastatic brain tumors should not be considered as a risk-free procedure and,
      while extremely rare, even fatal complications can occur after treatment.

PMID- 17041841
TI  - Endotherapy of Zenker's diverticulum using the needle-knife technique: long-term
      follow-up.
AB  - BACKGROUND AND STUDY AIMS: Endotherapy of Zenker's diverticulum by mucomyotomy of
      the bridge between the diverticulum and the esophageal lumen has been introduced
      as a promising alternative to surgical techniques. However the data on long-term
      clinical outcome are limited. After poor results in four patients treated by
      argon plasma coagulation, we studied the efficacy and the long-term outcome of
      dissection using a needle-knife in a consecutive series of patients. PATIENTS AND
      METHODS: Between December 2001 and November 2004, 31 consecutively treated
      symptomatic patients (18 men; median age 69 years; range 52-92) with Zenker's
      diverticulum were enrolled into this retrospective study. In all cases
      mucomyotomy was performed with a needle-knife with the patient under conscious
      sedation. The procedure was repeated in the case of incomplete relief from
      dysphagia or of recurrent symptoms during follow-up. All patients completed
      questionnaires on the frequency and severity of dysphagia, using a numeric
      analogue scale, ranging from 0 (never/none/excellent) to 10 (each time of
      swallowing/very severe/very bad). RESULTS: Endoscopic mucomyotomy was achieved in
      all 31 patients, with initial symptomatic improvement. Repeat treatment was
      required in 10 patients after a mean of 5.3 months, due to recurrence of
      symptoms. During a mean follow-up period of 26 months (range 14-49), 26 patients
      (84%) had long-term success of variable degree (65% with no or minimal remaining
      symptoms); four patients (13%) had insufficient relief and wanted a repeat
      treatment; and one patient (3%) underwent surgery. The success rate in the entire
      group was 84% (26/31) including those with repeat treatment, and 61% (19/31) if
      only success following a single treatment session was counted. Minor
      complications such as subcutaneous or mediastinal emphysema were observed in 23%
      and were conservatively managed. There were no major complications. CONCLUSIONS:
      A single needle-knife mucomyotomy procedure can achieve long-term symptomatic
      improvement in about two out of three cases of Zenker's diverticulum. The success
      rate can be increased to above 80% by repeated sessions. Minor complications
      occur frequently but they can be conservatively managed. Major complications were
      not observed. Further long-term studies are warranted to elucidate the role of
      endoscopy as a definitive single treatment, with determination of prognostic
      parameters for a successful long-term outcome.

PMID- 17041842
TI  - Food safety revisited.

PMID- 17041843
TI  - Are second-line drugs necessary to control multidrug-resistant tuberculosis?

PMID- 17041844
TI  - Human bocavirus: developing evidence for pathogenicity.

PMID- 17041845
TI  - Use of streptogramin growth promoters in poultry and isolation of streptogramin
      resistant Enterococcus faecium from humans.
AB  - BACKGROUND: Virginiamycin use in poultry selects for Enterococcus faecium with
      cross-resistance to quinupristin-dalfopristin, a drug for vancomycin-resistant E.
      faecium in humans. We conducted an epidemiologic study of poultry exposures as
      risk factors for human carriage of quinupristin-dalfopristin-resistant E.
      faecium. METHODS: Rectal or fecal samples for E. faecium testing were obtained
      from 567 newly admitted hospital patients and 100 healthy vegetarians.
      Participants were interviewed regarding poultry exposure. Retail poultry washes
      (160 conventional and 26 antibiotic free) were also tested for the presence of E.
      faecium. Constitutive and inducible quinupristin-dalfopristin resistance were
      assessed in E. faecium isolates, and resistance genes were identified by
      polymerase chain reaction. RESULTS: E. faecium was isolated from 105 patients, 65
      vegetarians, and 77 conventional and 23 antibiotic-free poultry washes.
      Constitutive quinupristin-dalfopristin resistance was absent in human E. faecium,
      but 56% of conventional poultry isolates were quinupristin-dalfopristin
      resistant. Inducible quinupristin-dalfopristin resistance was more common in
      samples from patients than in those from vegetarians and in washes of
      conventional than antibiotic-free poultry. Higher poultry consumption was
      associated with inducible quinupristin-dalfopristin resistance. vatE was present
      in 38% of E. faecium isolates from patients and none from vegetarians. Touching
      raw poultry was associated with the presence of vatE. CONCLUSIONS: Poultry
      exposure is associated with a quinupristin-dalfopristin resistance gene and
      inducible quinupristin-dalfopristin resistance in human fecal E. faecium. The
      continued use of virginiamycin may increase the potential for streptogramin
      resistant E. faecium infection in humans.

PMID- 17041846
TI  - An outbreak of gastrointestinal illness and erythema nodosum from grated carrots
      contaminated with Yersinia pseudotuberculosis.
AB  - BACKGROUND: Outbreaks of Yersinia pseudotuberculosis infection have been
      epidemiologically linked to fresh produce, but the bacterium has not been
      recovered from the food items implicated. In May 2003, a cluster of
      gastrointestinal illness and erythema nodosum was detected among schoolchildren
      who had eaten lunches prepared by the same institutional kitchen. METHODS: We
      conducted a case-control study and trace-back, environmental, and laboratory
      investigations. Case patients had culture-confirmed Y. pseudotuberculosis O:1
      infection, erythema nodosum, or reactive arthritis. Bacterial isolates from
      clinical and environmental samples were compared using pulsed-field gel
      electrophoresis (PFGE). RESULTS: Of 7392 persons at risk, 111 (1.5%) met the case
      definition; 76 case patients and 172 healthy control subjects were enrolled in
      the case-control study. Only raw grated carrots were significantly associated
      with illness in a logistic-regression model (multivariable odds ratio, 5.7 [95%
      confidence interval, 1.7-19.5]); a dose response was found for increasing amount
      of consumption. Y. pseudotuberculosis O:1 isolates from 39 stool specimens and
      from 5 (42%) of 12 soil samples that contained carrot residue and were obtained
      from peeling and washing equipment at the production farm were indistinguishable
      by PFGE. CONCLUSIONS: Carrots contaminated early in the production process caused
      a large point-source outbreak. Our findings enable the development of evidence
      based strategies to prevent outbreaks of this emerging foodborne pathogen.

PMID- 17041847
TI  - Impact of vitamin A on selected gastrointestinal pathogen infections and
      associated diarrheal episodes among children in Mexico City, Mexico.
AB  - BACKGROUND: The overall effect of vitamin A supplementation on diarrheal disease
      in community trials may result from its effect on specific diarrheal pathogens.
      METHODS: We conducted a placebo-controlled, double-blind trial of the
      prophylactic effect of vitamin A on gastrointestinal pathogen infections and
      clinical symptoms among 188 children in Mexico City, Mexico, from January 1998 to
      May 1999. Children 6-15 months of age were randomly assigned to receive either a
      vitamin A supplement (for children <12 months of age, 20,000 international units
      [IU] of retinol; for children > or =12 months of age, 45,000 IU of retinol) every
      2 months or a placebo and were followed for up to 15 months. Stool samples,
      collected semimonthly, were screened for enteropathogenic Escherichia coli
      (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC),
      enteroinvasive E. coli (EIEC), and Giardia lamblia. RESULTS: Vitamin A
      supplementation reduced the prevalence of EPEC infections (rate ratio [RR], 0.52
      [95% confidence interval {CI}, 0.23-0.86]) and led to shorter durations of both
      EPEC and ETEC infections. Supplementation also reduced the prevalence of EPEC
      associated diarrhea (RR, 0.41 [95% CI, 0.16-1.00]), EPEC-associated fever (RR,
      0.15 [95% CI, 0.02-0.98]), and G. lamblia-associated fever (RR, 0.27 [95% CI,
      0.13-0.80]). Finally, children who received vitamin A supplementation had shorter
      durations of EPEC-associated diarrhea than did children who did not receive
      supplementation but had longer durations of G. lamblia-associated diarrhea.
      CONCLUSIONS: These results suggest that the effect of vitamin A supplementation
      on clinical outcomes may be pathogen dependent.

PMID- 17041848
TI  - Antituberculosis drug resistance in the south of Vietnam: prevalence and trends.
AB  - BACKGROUND: There is limited evidence that the DOTS (directly observed therapy,
      short course) strategy for tuberculosis (TB) control can contain the emergence
      and spread of drug resistance in the absence of second-line treatment. We
      compared drug-resistance levels between 1996 and 2001 in the south of Vietnam, an
      area with a well-functioning DOTS program. METHODS: Sputum specimens were
      collected from consecutively diagnosed patients with smear-positive TB at 40
      randomly selected public TB clinics. Mycobacterium tuberculosis isolates were
      tested for susceptibility to first-line drugs. RESULTS: Among 888 new patients in
      2001, resistance to any drug was observed in 238 (26.3%), resistance to isoniazid
      was observed in 154 (16.6%), resistance to rifampin was observed in 22 (2.0%),
      resistance to ethambutol was observed in 12 (1.1%), resistance to streptomycin
      was observed in 173 (19.4%), and resistance to both isoniazid and rifampicin
      (multidrug resistance [MDR]) was observed in 20 (1.8% [95% confidence interval,
      1.0%-3.3%]). Among 136 previously treated patients in 2001, any resistance was
      observed in 89 (62.9%), and MDR was observed in 35 (23.2%). The prevalence of any
      drug resistance and of streptomycin resistance among new patients had decreased
      significantly (P<.01) since 1996; there was no increase in the prevalence of MDR.
      CONCLUSION: The prevalence of drug resistance decreased despite high initial
      levels of resistance to isoniazid and streptomycin and despite the absence of
      second-line treatment. Therefore, a DOTS program can contain drug-resistant TB in
      this setting.

PMID- 17041850
TI  - A live experimental vaccine against Burkholderia pseudomallei elicits CD4+ T cell
      mediated immunity, priming T cells specific for 2 type III secretion system
      proteins.
AB  - Burkholderia pseudomallei is the etiological agent of melioidosis, a serious
      human disease for which no vaccine is available. Immunization of susceptible
      BALB/c mice with the live attenuated mutant B. pseudomallei ilvI (referred to as
      "2D2") generated significant, although incomplete, immunity. Splenic B.
      pseudomallei-specific T cells, detected in immunized mice, proliferated and
      produced interferon-gamma in vitro in response to dead bacteria. Assessment of T
      cell antigen specificity indicated that subpopulations of B. pseudomallei
      reactive T cells were responsive to BopE, a type III secretion system (TTSS)
      effector protein, and to a lesser extent to BipD, a TTSS translocator protein.
      Increased survival of severe combined immunodeficient mice adoptively transferred
      with T cells from immunized mice, compared with that of naive T cell recipients,
      demonstrated that immunization with 2D2 generated T cell-mediated immunity. CD4+
      and CD8+ cell depletion studies demonstrated that CD4+ cells, but not CD8+ cells,
      mediated this protection in vivo. Thus, CD4+ T cells can mediate vaccine-induced
      immunity to experimental melioidosis.

PMID- 17041849
TI  - Deletion of a Mycobacterium tuberculosis proteasomal ATPase homologue gene
      produces a slow-growing strain that persists in host tissues.
AB  - The in vivo rate of proliferation of Mycobacterium tuberculosis, the causative
      agent of tuberculosis, has been linked to the rate of progression and severity of
      disease. Here, we report that deletion of the gene MT2175 (Rv2115c), a putative
      mycobacterial proteasome-associated AAA-ATPase, leads to a reduction in the
      growth rate of M. tuberculosis in vitro and in vivo. Despite the reduced growth,
      the mutant persisted, with slow and gradual clearance in mouse lungs. The mutant
      elicited reduced levels of interferon-gamma production in the lungs and, when
      used as an immunizing agent, provided significant protection against challenge
      with a virulent strain of M. tuberculosis. Expression of the genes lat and MT3159
      were highly up-regulated in the mutant. Thus, loss of MT2175 slows both in vitro
      and in vivo growth rates and compromises the lethality of M. tuberculosis in mice
      but has a minimal impact on the organism's ability to persist in host tissues.

PMID- 17041851
TI  - Protective immunity against respiratory tract challenge with Yersinia pestis in
      mice immunized with an adenovirus-based vaccine vector expressing V antigen.
AB  - The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a
      rapidly fatal disease. At present, no plague vaccines are available for use in
      the United States. One candidate for the development of a subunit vaccine is the
      Y. pestis virulence (V) antigen, a protein that mediates the function of the
      Yersinia outer protein virulence factors and suppresses inflammatory responses in
      the host. On the basis of the knowledge that adenovirus (Ad) gene-transfer
      vectors act as adjuvants in eliciting host immunity against the transgene they
      carry, we tested the hypothesis that a single administration of a replication
      defective Ad gene-transfer vector encoding the Y. pestis V antigen (AdsecV) could
      stimulate strong protective immune responses without a requirement for repeat
      administration. AdsecV elicited specific T cell responses and high IgG titers in
      serum within 2 weeks after a single intramuscular immunization. Importantly, the
      mice were protected from a lethal intranasal challenge of Y. pestis CO92 from 4
      weeks up to 6 months after immunization with a single intramuscular dose of
      AdsecV. These observations suggest that an Ad gene-transfer vector expressing V
      antigen is a candidate for development of an effective anti-plague vaccine.

PMID- 17041852
TI  - Identification of CT521 as a frequent target of Th1 cells in patients with
      urogenital Chlamydia trachomatis infection.
AB  - BACKGROUND: The human immune response to a Chlamydia trachomatis serovar D lysate
      was investigated in patients with urogenital C. trachomatis infection, to
      identify novel T cell targets. METHODS: A C. trachomatis lysate was fractionated
      on the basis of molecular mass, and each fraction was used to stimulate
      peripheral-blood mononuclear cells from patients with C. trachomatis infection.
      In frequently recognized fractions, proteins were identified by mass
      spectrometry, recombinantly expressed, and tested for T cell recognition.
      RESULTS: T cell recognition of the fractions was highly heterogeneous in patients
      with C. trachomatis infection (n=16). Four patients exhibited responses that were
      strongly targeted to antigens of 16-20-kDa molecular mass. Three proteins were
      identified in this fraction: CT043, CT511, and CT521. The T cell response to the
      individual recombinant proteins were investigated, and CT521 was found to induce
      the highest level of interferon (IFN)- gamma. The recognition of CT521 was
      investigated in a larger study population (n=41), and a positive IFN-gamma
      response was measured in 83% of the patients. Several T cell epitopes were
      identified in CT521; in particular, peptide 5 in the central part of the protein
      was frequently recognized by T cells (63%). CONCLUSION: We have identified a
      novel C. trachomatis antigen, CT521, that is frequently recognized in patients
      with urogenital C. trachomatis infection.

PMID- 17041853
TI  - Regulation of Staphylococcus aureus alpha-toxin gene (hla) expression by agr,
      sarA, and sae in vitro and in experimental infective endocarditis.
AB  - BACKGROUND: The Staphylococcus aureus global regulators--agr, sarA, and sae-
      coordinately control alpha-toxin gene (hla) expression in vitro. However, their
      relative in vivo contributions to hla expression, particularly in endovascular
      infections, have not been defined. METHODS: A plasmid-based hla-promoter:green
      fluorescent protein reporter system was constructed in 2 genetically related S.
      aureus strains: RN6390 (a natural sigma factor B [sigB]-deficient mutant), SH1000
      (a sigB-repaired variant of RN6390 lineage), and their respective agr, sarA,
      agr/sarA, and sae mutants. These strain sets were used to quantify hla expression
      in vitro and in an experimental infective endocarditis (IE) model using flow
      cytometry. RESULTS: In vitro, hla expression was positively modulated by all 3
      regulons (sae > agr/sarA > agr and sarA) in both RN6390 and SH1000 backgrounds.
      In the IE model, hla expression in cardiac vegetations was lower in all single
      mutants than in the respective parental strains (P<.05 for sae mutant) but was
      maintained at near-parental levels in the agr/sarA double mutant in both
      backgrounds. A similar finding was also observed in kidneys and spleens.
      CONCLUSIONS: These results indicate that, although several distinct regulatory
      circuits can affect hla expression in vitro and in vivo, sae appears to play a
      crucial role in this context.

PMID- 17041854
TI  - Human bocavirus infection in young children in the United States: molecular
      epidemiological profile and clinical characteristics of a newly emerging
      respiratory virus.
AB  - BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that
      was originally identified in the respiratory secretions of children with
      respiratory tract disease. To further investigate the epidemiological profile and
      clinical characteristics of HBoV infection, we screened infants and children <2
      years of age (hereafter referred to as "children") for HBoV. METHODS: Children
      for whom respiratory specimens submitted to a diagnostic laboratory tested
      negative for respiratory syncytial virus, parainfluenza viruses (types 1-3),
      influenza A and B viruses, and adenovirus, as well as asymptomatic children,
      underwent screening for HBoV by use of polymerase chain reaction (PCR).
      Respiratory specimens were obtained from the children from 1 January 2004 through
      31 December 2004. RESULTS: Twenty-two (5.2%) of the 425 children who had a
      respiratory specimen submitted to the diagnostic laboratory and 0 of the 96
      asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever,
      rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive
      children. Of the 17 children who had chest radiography performed, 12 (70.6%) had
      abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide
      polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two
      distinct HBoV genotypes circulated during the study period. CONCLUSIONS: HBoV is
      circulating in the United States and is associated with both upper and lower
      respiratory tract disease in infants and young children.

PMID- 17041855
TI  - Epidemiological profile and clinical associations of human bocavirus and other
      human parvoviruses.
AB  - BACKGROUND: Human bocavirus (HBoV) and PARV4 are newly discovered human
      parvoviruses. HBoV, which was first detected in respiratory samples, has a
      potential role in the development of human respiratory disease. The present study
      compared the frequencies, epidemiological profiles, and clinical backgrounds of
      HBoV and PARV4 infections with those of other respiratory virus infections, by
      evaluating diagnostic samples referred to the Specialist Virology Laboratory
      (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom). METHODS:
      Anonymized samples and study subject information were obtained from the
      respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4,
      B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and
      parainfluenza viruses by use of nested polymerase chain reaction. RESULTS: HBoV
      infection was detected in 47 (8.2%) of 574 study subjects, ranking third in
      prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak
      incidences of HBoV were noted among infants and young children (age, 6-24 months)
      during the midwinter months (December and January) and were specifically
      associated with lower respiratory tract infections. HBoV infections were
      frequently accompanied by other respiratory viruses (frequency, 43%), and they
      were more prevalent among individuals infected with other respiratory viruses
      (17%), frequently adenovirus or RSV. All respiratory samples were negative for
      PARV4. CONCLUSIONS: In the present study, HBoV was a frequently detected,
      potential respiratory pathogen, with a prevalence and an epidemiological profile
      comparable to those of RSV. Identification of HBoV infections may be clinically
      important in the future.

PMID- 17041856
TI  - Human papillomavirus genotypes and the cumulative 2-year risk of cervical
      precancer.
AB  - BACKGROUND: Prospective data on the risks of cervical precancer associated with
      specific human papillomavirus (HPV) genotypes are limited. METHODS: In 5060 women
      participating in the Atypical Squamous Cells of Undetermined Significance/Low
      Grade Squamous Intraepithelial Lesions Triage Study (ALTS), we determined the
      cumulative 2-year risks of cervical intraepithelial neoplasia (CIN) grade 2 or
      more severe (> or =CIN2) and of grade 3 or more severe (> or =CIN3) for 38
      individual HPV genotypes, as detected by polymerase chain reaction. RESULTS: The
      most common HPV genotypes detected at baseline, in descending order of
      prevalence, were 16, 52, 51, 31, 18, 53, 39, 56, 62, 59, and 58. When detected as
      a single-type HPV infection, HPV-16 had a 2-year cumulative risk of 50.6% (95%
      confidence interval [CI], 44.1%-57.2%) for > or =CIN2 and 39.1% (95% CI, 32.9%
      45.7%) for > or =CIN3. For other singly detected carcinogenic HPV types, the risk
      of > or =CIN2 ranged from 4.7% (for HPV-59) to 29.5% (for HPV-31), and the risk
      of > or =CIN3 ranged from 0.0% (for HPV-59) to 14.8% (for HPV-31). Multiple
      infections with HPV genotypes of different risk classes resulted in a risk that
      was similar to, and not significantly different from, the risk observed for the
      HPV genotype of the highest risk class. CONCLUSIONS: Genotype-specific HPV
      testing may be useful for identifying women with atypical squamous cells of
      undetermined significance and low-grade squamous intraepithelial lesions who are
      at higher and lower risk of prevalent and incipient cervical precancer.

PMID- 17041857
TI  - Humanized monoclonal antibody against West Nile virus envelope protein
      administered after neuronal infection protects against lethal encephalitis in
      hamsters.
AB  - Humans infected with West Nile virus (WNV) may clinically present with symptoms
      that are suggestive of neurological infection. Nearly all treatments of WNV
      disease have been effective in animal models only if administered before or soon
      after viral challenge. Here, we evaluated whether a potent neutralizing anti-WNV
      humanized monoclonal antibody (MAb), hE16, could improve the course of disease in
      a hamster model when administered after the virus had infected neurons in the
      brain. Five days after viral injection, WNV was detected in the brains of
      hamsters by cytopathic assay, quantitative reverse-transcription polymerase chain
      reaction, and immunohistochemical staining of WNV envelope in neurons. Notably,
      80%-90% of the hamsters treated 5 days after viral injection by intraperitoneal
      injection with hE16 survived the disease, compared with 37% of the placebo
      treated hamsters (P< or =.001). The hamsters that received hE16 directly in the
      brain also exhibited markedly improved survival rates, compared with those in the
      placebo-treated hamsters. In prospective experiments, hamsters with high levels
      of infectious WNV in their cerebrospinal fluid were also protected by hE16 when
      administered 5 days after viral injection. These experiments suggest that
      humanized MAbs with potent neutralizing activity are a possible treatment for
      human patients after WNV has infected neurons in the central nervous system.

PMID- 17041858
TI  - A randomized trial of treatment interruption before optimized antiretroviral
      therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG
      A5086.
AB  - BACKGROUND: The role of structured treatment interruption (STI) before optimized
      antiretroviral therapy (ART) in patients with drug-resistant human
      immunodeficiency virus type 1 (HIV-1) is uncertain. METHODS: AIDS Clinical Trial
      Group protocol A5086 was a prospective trial of 41 patients with multiple drug
      class-resistant HIV who were randomized to undergo a 16-week STI followed by
      optimized ART (STI) or immediate optimized ART (no STI). The primary end point
      was the proportion of subjects with HIV-1 RNA loads <400 copies/mL 48 weeks after
      randomization. RESULTS: Of 39 evaluable patients, 4 (19%) in the STI arm and 6
      (33%) in the no STI arm had HIV-1 RNA loads <400 copies/mL at 48 weeks (P=.44).
      Median changes from baseline in CD4+ cell counts and HIV-1 RNA loads were similar
      for both arms. Standard genotypes at the end of STI showed nearly complete
      reversion to wild-type virus in a minority of patients (n=5; 28%). Virus with 3
      drug class resistance reemerged even when ART included only 1 or 2 drug classes.
      Single-genome sequencing showed that each genome encoded resistance mutations for
      3 drug classes. CONCLUSIONS: A 16-week STI before optimized ART did not improve
      virologic response. Genetic analyses strongly suggest that virologic failure
      resulted from the reemergence of virus present before STI that encoded 3-drug
      class resistance on the same genome.

PMID- 17041859
TI  - Viral decay dynamics in HIV-infected patients receiving ritonavir-boosted
      saquinavir and efavirenz with or without enfuvirtide: a randomized, controlled
      trial (HIV-NAT 012).
AB  - The availability of enfuvirtide enables assessment of whether human
      immunodeficiency virus (HIV) decay can be enhanced by targeting reverse
      transcriptase, protease, and fusion. We performed a 12-week study of 22 patients
      randomized to receive ritonavir-boosted saquinavir and efavirenz with (the 3
      target arm) or without (the 2-target arm) enfuvirtide. We observed no difference
      in the mean+/-SD elimination-rate constant for overall decay (0.142+/-0.040 per
      day and 0.128 +/- 0.033 per day in the 2- and 3-target arms, respectively; P>.1)
      or for modeled first-phase decay rate (-0.62+/-0.34 per day and -0.51+/-0.16 per
      day; P>.1). Antiretroviral therapy that inhibits HIV reverse transcriptase and
      protease exerts potent antiviral effects that might not be augmented by the
      addition of an HIV fusion inhibitor.

PMID- 17041860
TI  - Epstein-Barr virus infects B and non-B lymphocytes in HIV-1-infected children and
      adolescents.
AB  - Epstein-Barr virus (EBV) is a widespread, persistent herpesvirus that can
      transform B cells and that is associated with malignant lymphomas. EBV dynamics
      and specific immunity in human immunodeficiency virus (HIV)-1-infected children
      are unknown. We found that, in 74% of EBV-seropositive, HIV-1-infected children,
      EBV DNA loads at the start of highly active antiretroviral therapy (HAART) were
      comparable with those in acutely EBV-infected, HIV-negative children. EBV DNA
      load remained elevated in most HIV-1-infected children for months to years of
      follow-up. Frequencies of interferon-gamma-producing EBV-specific CD8+ T cells
      were comparable with those in healthy control children, and antibodies to EBV
      nuclear antigen were detected in 73% of EBV-seropositive children. Detectable EBV
      DNA load was not correlated with HIV-1 RNA level or with CD4+ T cell count
      increase after the start of HAART. Because of its resemblance to chronic active
      EBV, we studied the cellular tropism of EBV in these patients. EBV DNA was found
      not only in the CD19+ B cell fraction but also--at stable levels--in the CD4+ and
      CD8+ T cell fractions. Although the reason for the aberrant T cell tropism of EBV
      remains unclear, these data may provide an explanation for the differential EBV
      dynamics in the presence of normal serological findings.

PMID- 17041861
TI  - Early procoagulant shift in the bronchoalveolar compartment of patients with
      secondary peritonitis.
AB  - BACKGROUND: In acute respiratory distress syndrome or pneumonia, a procoagulant
      shift is observed in bronchoalveolar lavage fluid (BALF). The effect of a
      primarily extrapulmonary infection on coagulation and fibrinolysis in the
      pulmonary compartment is unclear. METHODS: In 35 patients, 87 bronchoalveolar
      lavages were performed on the day of operation for secondary peritonitis (day 0)
      and on days 2 and 3 after surgery. Two noninfectious control groups were
      included: subjects undergoing bronchoalveolar lavage after elective surgery (n=8)
      and those undergoing long-term mechanical ventilation (n=10). RESULTS: In BALF
      from patients with peritonitis, a tissue factor (TF)/factor VIIa-mediated
      activation of coagulation was shown (high levels of thrombin-antithrombin
      complexes). Levels of fibrinolysis activators decreased rapidly after day 0,
      whereas levels of inhibitors increased. The net effect was reduced fibrinolysis
      (plasminogen activator activity). The sequential comparison of plasma levels of
      TF pathway inhibitor showed higher levels in patients who died (28-day mortality;
      P<.001). Sequential levels of TF in BALF were higher in patients with low PaO2 :
      FiO2 ratios (<200; P=.039). Differences between patients and control subjects
      were more pronounced in BALF than in plasma. CONCLUSIONS: Secondary peritonitis
      induces an early activation of the coagulation and inhibition of fibrinolysis in
      the systemic and bronchoalveolar compartments, possibly via a compartmentalized
      response. This imbalance may be associated with reduced oxygen delivery and an
      adverse outcome in secondary peritonitis.

PMID- 17041863
TI  - Elevated plasma levels of limulus amoebocyte lysate-reactive material.

PMID- 17041864
TI  - Chloride uptake and base secretion in freshwater fish: a transepithelial ion
      transport metabolon?
AB  - Despite all the efforts and technological advances during the last few decades,
      the cellular mechanisms for branchial chloride uptake in freshwater (FW) fish are
      still unclear. Although a tight 1 : 1 link with HCO-3 secretion has been
      established, not much is known about the identity of the ion-transporting
      proteins involved or the energizing steps that allow for the inward transport of
      Cl- against the concentration gradient. We propose a new model for Cl- uptake in
      FW fish whereby the combined action of an apical anion exchanger, cytoplasmic
      carbonic anhydrase, and basolateral V-type H+ -ATPase creates a local [HCO-3]
      high enough to energize Cl- uptake. Our model is based on analyses of structure
      function relationships, reinterpretation of previous results, and novel
      observations about gill cell subtypes and immunolocalization of the V-H+ -ATPase.

PMID- 17041865
TI  - The coupled evolution of breathing and locomotion as a game of leapfrog.
AB  - Because the increase in metabolic rate related to locomotor activity places
      demands on the cardiorespiratory apparatus, it is not surprising that the
      evolution of breathing and of locomotion are coupled. As the respiratory faculty
      becomes more refined, increasingly aerobic life strategies can be explored, and
      this activity is in turn expedited by a higher-performance respiratory apparatus.
      This apparent leapfrogging of respiratory and locomotor faculties begins in
      noncraniate chordates and continues in water-breathing and air-breathing
      vertebrates. Because both locomotor and cardiorespiratory activities are
      coordinated in the brain, neurological as well as biochemical coupling is
      evident. In spite of very different breathing mechanisms in various vertebrate
      groups, the basic respiratory control mechanisms appear to have been conserved,
      and respiratory-locomotor coupling is evident in all classes of vertebrates.
      Hypaxial body wall muscles that were strictly locomotor in fish have respiratory
      function in amniotes, but some locomotor function remains in all groups.

PMID- 17041866
TI  - Coupling of the respiratory rhythm in fish with activity in hypobranchial nerves
      and with heartbeat.
AB  - Fish have a central respiratory pattern generator (CRPG) in the brain stem that
      initiates activity in a series of cranial nerves innervating respiratory muscles.
      These nerves burst sequentially in the order of their rostrocaudal distribution
      in the central nervous system. When respiratory drive is high, this activity
      spreads caudally to occipital and anterior spinal neurons that project via the
      hypobranchial nerves to stimulate hypaxial muscles, causing active jaw abduction.
      The CRPG may also recruit the heart. Fish, like mammals, show respiratory
      components in the intrinsic variability of heart rate (HRV). Cardiorespiratory
      synchrony in the dogfish is driven by bursting activity in the cardiac branches
      of the vagus nerve, which emanates from preganglionic neurons in the dorsal vagal
      motor nucleus. A respiratory component in HRV is difficult to discriminate in
      other species, requiring the use of power spectral analysis and the subsequent
      elimination of aliased components.

PMID- 17041867
TI  - Lung and buccal ventilation in the frog: uncoupling coupled oscillators.
AB  - The frog, with two distinct ventilatory acts, provides a useful model to
      investigate the prospective interaction of two oscillators in generating the
      respiratory rhythm. Building on evidence supporting the existence of separate
      oscillators generating buccal and lung ventilation, we have attempted to uncouple
      the two rhythms in the isolated brain stem preparation. Opioid preferentially
      inhibits the lung rhythm, suggesting an uncoupling of the lung from the buccal
      oscillator. Reduction of the superfusate chloride concentration alters both the
      buccal and the lung rhythms. Joint application of opioid and reduced-chloride
      superfusate leads to an increase in the variability of the buccal burst-to-lung
      burst intervals. This increase in variability suggests that chloride-mediated
      mechanisms are involved in coupling the buccal oscillator to the lung oscillator.
      Given the results from these interventions, we propose a simple schematic model
      of the frog respiratory rhythm generator, outlining the coupling of the lung and
      buccal oscillators.

PMID- 17041868
TI  - Function of intracoelomic septa in lung ventilation of amniotes: lessons from
      lizards.
AB  - Aspiration breathing is the dominant mechanism of lung inflation among extant
      amniotes. However, aspiration has two fundamental problems associated with it:
      paradoxical visceral translation and partial lung collapse. These can constrain
      the inspiratory tidal volume, reduce the effective lung ventilation, and
      ultimately curtail the aerobic capacity of an animal. Separation of the pleural
      and peritoneal cavities by an intracoelomic septum can restrict the cranial shift
      of abdominal viscera and provide structural support to the caudal lung surface. A
      muscular septum, such as the diaphragm of mammals or the diaphragmaticus of
      crocodilians, can exert active control over visceral translation and the degree
      of lung inflation. To a lesser degree, a nonmuscular septum can also function as
      a passive barrier when stretched taut by rib rotation. Studies of the posthepatic
      septum in teiid lizards and the postpulmonary septum in varanid lizards
      underscore the importance of nonmuscular septa in aspiration. These septa provide
      plausible functional models that help us infer the evolution of mammalian and
      avian lung ventilatory systems, respectively.

PMID- 17041869
TI  - Effects of the natural tidal cycle and artificial temperature cycling on Hsp
      levels in the tidepool sculpin Oligocottus maculosus.
AB  - The rocky intertidal zone is characterized by a predictable cycle of
      environmental change cued by the ebb and flow of the tides. Tidepools are thus an
      excellent environment in which to determine whether predictability of
      environmental change can entrain an endogenous rhythmicity in heat shock protein
      (Hsp) levels. In this study, we monitored changes in Hsp mRNA and protein levels
      that occurred over the tidal cycle in tidepool sculpins and investigated whether
      there was an endogenous tidal rhythm in Hsp expression that persisted once the
      sculpins were transferred to a stable environment. Fluctuations in the tidepool
      environment increased hsc70, hsp70, and hsp90 mRNA levels, which translated into
      increased Hsc/Hsp70 and Hsp90 protein levels; however, this was not due to an
      endogenous tidal rhythm in Hsp levels because sculpins held under constant
      conditions did not show any rhythmicity in the expression of these genes. By
      exposing sculpins to an artificial temperature cycling regime that mimicked the
      temperature changes of a mid-intertidal pool, we were able to account for the
      direct role of temperature in regulating Hsp expression. However, there are
      additional extrinsic factors that likely integrate with temperature and result in
      differences between the hsp induction profiles that were observed in sculpins
      inhabiting their natural environment and those in cycling conditions in the
      laboratory.

PMID- 17041870
TI  - Swimming performance, metabolic rates, and their correlates in the Iceland
      scallop Chlamys islandica.
AB  - The dramatic escape response of some scallops is modified by reproductive
      investment and by acclimation temperature. Despite considerable knowledge of the
      physiology of the escape response, functional links between escape response
      performance, organismal rates of oxygen uptake, and tissue metabolic capacities
      are little known. We measured oxygen consumption rates (standard, maximal, and
      aerobic scope), escape behavior (initial and repeat performance), tissue mass,
      condition index, protein content, and tissue metabolic capacities in the Iceland
      scallop Chlamys islandica to examine links between these parameters. Postexercise
      oxygen consumption rates were positively linked to contraction rate (repeat test)
      and to pyruvate kinase activity in the adductor muscle but negatively linked to
      digestive gland wet mass. Swimming behavior was mainly related to activity of
      glycolytic enzymes, and enzymatic activities were related to anatomic parameters.
      Scallop behavior and physiology change with size, both within our samples and on
      a larger scale. Small scallops showed more intense swimming activity and had
      higher arginine kinase activities but lower glycolytic enzyme activities in their
      adductor muscle than larger scallops. This corresponds to the ontogenetic change
      in susceptibility to predation and in habitat use observed in C. islandica.

PMID- 17041871
TI  - Wiping behavior, skin resistance, and the metabolic response to dehydration in
      the arboreal frog Phyllomedusa hypochondrialis.
AB  - Several species of arboreal frogs secrete lipids from cutaneous glands and wipe
      these secretions over the body surfaces to reduce evaporative water losses.
      Following wiping, frogs become immobile in water-conserving postures, and some
      have suggested they are torpid. Here we report wiping behaviors and the
      physiological correlates of immobile postures in the arboreal monkey frog
      Phyllomedusa hypochondrialis. Skin resistance to water loss was comparatively
      high, and rates of evaporation were as low as 4% of that from a free water
      surface. Standard rates of metabolism (SMR) varied from 89 microL O2 h(-1) at 18
      degrees C to 316 microL O2 h(-1) at 34 degrees C and were sensitive to both
      temperature (T) and body mass (W; mL O2 h(-1) = 0.016W0.642 x 10(0.030T)). The
      mean SMR did not change significantly during four consecutive days of dehydration
      when animals lost 19%-34% of body mass. Therefore, it appears these frogs do not
      routinely depress metabolic rates following wiping. However, some individuals
      that lost higher percentages of body water exhibited trends of decreasing oxygen
      consumption, suggesting that suppression of metabolic rates might occur at
      greater levels of body water deficit or perhaps during a slower course of
      dehydration than imposed by our experiments (e.g., individuals that are secluded
      during periods of drought).

PMID- 17041872
TI  - Influence of the nest environment on bone mineral content in hatchling painted
      turtles (Chrysemys picta).
AB  - We performed an experiment at a field site in north-central Nebraska to assess
      the role of the nest environment in inducing variation in bone mineral content in
      hatchling painted turtles Chrysemys picta (Schneider 1783). The contents of
      several newly constructed nests were manipulated by reciprocal transplant, after
      which the eggs were allowed to incubate for 8 wk under natural conditions. The
      nests were then excavated, and the eggs were brought into the laboratory to
      complete incubation and hatch under standard conditions of temperature and
      moisture. The hatchlings were killed, and their carcasses and residual yolks were
      analyzed separately for calcium and phosphorus. More of the random variation in
      carcass calcium and phosphorus was related to the nest in which eggs incubated
      (37% and 42%, respectively) than was associated with the clutch of origin (21%
      and 37%). Moreover, hatchlings from some nests contained substantially more
      calcium and phosphorus than did hatchlings from other nests, both in terms of the
      absolute amounts of the elements in their carcasses (pointing to variation in
      body size) and in terms of the concentrations of those elements (pointing to
      variation in bone density). The amounts of calcium and phosphorus in carcasses of
      hatchlings were positively correlated with changes in mass of their eggs during
      the 8 wk that the eggs incubated in nests in the field, thereby indicating that
      the influence of the nest environment on developing embryos probably was mediated
      by water exchanges experienced by the eggs. These findings indicate that
      developmental plasticity underlies a major fraction of the variation in mineral
      content of hatchling painted turtles emerging from nests in the field. Phenotypic
      variation attributable to plasticity consequently needs to be addressed in models
      for life-history evolution of painted turtles and other chelonians producing eggs
      with soft, flexible shells.

PMID- 17041874
TI  - Physiological response to feeding in little penguins.
AB  - Specific dynamic action (SDA), the increase in metabolic rate above resting
      levels that accompanies the processes of digestion and assimilation of food, can
      form a substantial part of the daily energy budget of free-ranging animals. We
      measured heart rate (fH) and rate of oxygen consumption (VO2) in 12 little
      penguins while they digested a meal of sardines in order to determine whether
      they show specific dynamic action. In contrast to some studies of other penguin
      species, little penguins showed a substantial SDA, the magnitude of which was
      proportional to the size of the meal. The energy utilized in SDA was equivalent
      to 13.4% of the available energy content of the fish. Furthermore, animals such
      as penguins that forage in a cold environment will probably expend further energy
      in heating their food to body temperature to facilitate efficient digestion. It
      is estimated that this additional energy expenditure was equivalent to 1.6%-2.3%
      of the available energy content of the fish, depending on the time of year and
      therefore the temperature of the water. Changes in fH during digestion were
      qualitatively similar to those in VO2, implying that there were no substantial
      circulatory adjustments during digestion and that the relationship between fH and
      VO2 in penguins is unaffected by digestive state.

PMID- 17041873
TI  - Hummingbirds fuel hovering flight with newly ingested sugar.
AB  - We sought to characterize the ability of hummingbirds to fuel their energetically
      expensive hovering flight using dietary sugar by a combination of respirometry
      and stable carbon isotope techniques. Broadtailed hummingbirds (Selasphorus
      platycercus) were maintained on a diet containing beet sugar with an isotopic
      composition characteristic of C3 plants. Hummingbirds were fasted and then
      offered a solution containing cane sugar with an isotopic composition
      characteristic of C4 plants. By monitoring the rates of CO2 production and O2
      consumption, as well as the stable carbon isotope composition of expired CO2, we
      were able to estimate the relative contributions of carbohydrate and fat, as well
      as the absolute rate at which dietary sucrose was oxidized during hovering. The
      combination of respirometry and carbon isotope analysis revealed that
      hummingbirds initially oxidized endogenous fat following a fast and then
      progressively oxidized proportionately more carbohydrates. The contribution from
      dietary sources increased with each feeding bout, and by 20 min after the first
      meal, dietary sugar supported approximately 74% of hovering metabolism. The
      ability of hummingbirds to satisfy the energetic requirements of hovering flight
      mainly with recently ingested sugar is unique among vertebrates. Our finding
      provides an example of evolutionary convergence in physiological and biochemical
      traits among unrelated nectar-feeding animals.

PMID- 17041875
TI  - Yolk antioxidants vary with male attractiveness and female condition in the house
      finch (Carpodacus mexicanus).
AB  - The manipulation of egg content is one of the few ways by which female birds can
      alter offspring quality before hatch. Lipid-soluble vitamins and carotenoids are
      potent antioxidants. Female birds deposit these antioxidants into eggs in
      variable amounts according to environmental and social conditions, and the
      quantities deposited into eggs can have effects on offspring health and
      immunological condition. Allocation theory posits that females will alter the
      distribution of resources according to mate quality, sometimes allocating
      resources according to the differential allocation hypothesis (DAH), investing
      more in offspring sired by better-quality males, and other times allocating
      resources according to a compensatory strategy, enhancing the quality of
      offspring sired by lower-quality males. It is unknown, however, whether
      antioxidants are deposited into eggs according to the DAH or a compensatory
      strategy. We examined deposition patterns of yolk antioxidants (including vitamin
      E and three carotenoids) in relation to laying order, mate attractiveness, female
      condition, and yolk androgen content in the house finch (Carpodacus mexicanus).
      Female house finches deposited significantly more total antioxidants into eggs
      sired by less attractive males. Additionally, yolk antioxidant content was
      significantly positively correlated with female condition, which suggests a cost
      associated with the deposition of antioxidants into eggs. Finally, concentrations
      of antioxidants in egg yolks were positively correlated with total yolk androgen
      content. We suggest that yolk antioxidants are deposited according to a
      compensatory deposition strategy, enabling females to improve the quality of
      young produced with less attractive males. Additionally, yolk antioxidants may
      act to counter some of the detrimental effects associated with high levels of
      yolk androgens in eggs and, thus, may exert a complementary effect to yolk
      androgens.

PMID- 17041876
TI  - Angiotensin II and aldosterone increase with fasting in breeding adult male
      northern elephant seals (Mirounga angustirostris).
AB  - The renin-angiotensin-aldosterone system (RAAS) appears to contribute
      significantly to osmoregulation of fasting northern elephant seal (Mirounga
      angustirostris) pups; however, RAAS has not been characterized in fasting adult
      seals. Therefore, this study examined the contribution of RAAS to water turnover
      rates in fasting adult male northern elephant seals. Blood samples were obtained
      twice during their breeding fast at an interval of 6.5 wk, and water efflux rate
      was estimated by isotopic dilution during the same period. Serum electrolytes
      (Na+, K+, Cl-) and osmolality were unaltered between the two sampling periods,
      indicating ionic and osmotic homeostasis during the fast. Despite the lack of an
      increase in vasopressin, serum angiotensin II and aldosterone were increased and
      were significantly and positively correlated. Changes in aldosterone
      concentration and water efflux rate were significantly and negatively correlated,
      suggesting that the greater the increase in aldosterone, the smaller the loss of
      water. Adult male seals maintain ionic and osmotic homeostasis similar to that of
      fasting weaned pups, and this homeostasis appears to be mediated, at least in
      part, by RAAS, which probably contributes to increased water retention as well.
      The hormonal mechanisms by which northern elephant seals maintain water and
      electrolyte balance during fasting conditions appear to be similar regardless of
      age.

PMID- 17041877
TI  - Determination of the mutation spectrum of the EXT1/EXT2 genes in British
      Caucasian patients with multiple osteochondromas, and exclusion of six candidate
      genes in EXT negative cases.
AB  - We describe here the spectrum and distribution of mutations in the EXT1 and EXT2
      genes in the largest reported British Caucasian multiple osteochondromas (MO)
      population. Furthermore, we report for the first time the screening of the EXT1
      and EXT2 promoters, 5'UTRs, and 3'UTRs, and exclude six potential MO candidate
      genes in individuals without a detectable mutation within the coding region of
      EXT1 and EXT2. The coding exons of EXT1 and EXT2 were screened in 72 unrelated
      probands affected with MO. Forty-six different mutations were identified in 56
      probands, of which 29 were novel. Mutation in the EXT1 and EXT2 genes each
      accounted for 50% of the mutations identified. Of the 72 probands, 42 were of
      British Caucasian descent, which when added to the 41 British Caucasian families
      previously reported from our total cohort, gave a total of 83 families. This
      cohort's proportional frequency for EXT1/EXT2 mutation was 53%/47%. We also
      validated the technique of high-resolution melting analysis in a blind study
      using 27 unique EXT1 or EXT2 mutations. This technique was found to be sensitive
      with a detection rate of 100% regarding heterozygote detection for EXT mutation
      scanning. Furthermore, this technique has a very high throughput and is very cost
      effective.

PMID- 17041879
TI  - Autocalibrating parallel imaging of in vivo trabecular bone microarchitecture at
      3 Tesla.
AB  - In this work the generalized autocalibrating partially parallel acquisition
      (GRAPPA) technique was implemented with modified reconstruction and applied to in
      vivo high-resolution (HR) magnetic resonance imaging (MRI) of the trabecular bone
      microarchitecture at 3 Tesla (T) with a multiple-acquisition balanced steady
      state free precession (b-SSFP) sequence. Trabecular bone is made up of a network
      of microstructures (80-140 microm), and its structural deterioration is
      associated with the skeletal metabolic disorder osteoporosis. HR-MRI is a
      promising noninvasive tool for assessing the trabecular microarchitecture in
      vivo, but it involves long acquisition times. Using partially parallel imaging
      (PPI) to accelerate the acquisition may help mitigate this shortcoming and allow
      more flexibility in protocol design. In this study the effects of GRAPPA-based
      reconstruction on image characteristics and the measurement of trabecular bone
      structural parameters were evaluated. Initial studies showed that image quality
      and depiction of microstructure were preserved in the GRAPPA-based
      reconstruction, indicating the feasibility of PPI in HR-MRI of trabecular bone.
      The results also demonstrated the potential of PPI for increasing the signal-to
      noise ratio (SNR) efficiency of multiple-acquisition b-SSFP imaging protocols.

PMID- 17041880
TI  - How many nuclei make an embryo sac in flowering plants?
AB  - Research on early-divergent angiosperms, including Amborella, the putative sister
      to all other extant angiosperms, is increasingly used as a yardstick to infer the
      nature of the hypothetical ancestral angiosperm. Some traits are relatively
      diverse (and hence relatively labile) in this phylogenetic grade, compared with
      the more derived eudicot clade, in which developmental patterns have become
      increasingly canalized. One of the many mysteries surrounding the origin of the
      angiosperms is the evolutionary origin of the Polygonum-type embryo sac
      (monosporic, eight-nucleate and seven-celled) that occurs in the majority of
      flowering plants. Observations on the megagametophyte of Amborella are
      conflicting, but a recent report of a supernumerary synergid in this genus raises
      the question of whether the Polygonum-type embryo sac is derived by duplication
      of a four-nucleate structure or by reduction from a multicellular structure.

PMID- 17041881
TI  - Concerning the preparation and use of substances with a magnetic susceptibility
      equal to the magnetic susceptibility of air.
AB  - In this work it is demonstrated that the susceptibility of diamagnetic
      substances, such as water and agarose gel, can easily be tuned to the
      susceptibility of air by the addition of a proper amount of strongly paramagnetic
      ions, in this case 16.6 +/- 0.1 mM holmium(III). The resultant air-equivalent
      substances are shown to allow the creation of objects that do not disturb the
      static magnetic field of the scanner and hence do not invoke susceptibility
      artifacts, regardless of the objects' shape, size, and orientation with respect
      to B(0), and regardless of the pulse sequence being used. The addition of the
      proper amount of holmium(III) to aqueous solutions and gels is further shown to
      exert a negligible influence on the chemical shift and to cause a moderate
      increase of the relaxation rates 1/T(1) and 1/T(2). The results indicate the
      potential of air-equivalent substances for many purposes, including construction
      of artifact-free test objects; experimental setups and accessory devices;
      investigation of systems that contain air cavities, gas bubbles, etc.; and
      monitoring of system-related and object-induced field disturbances.

PMID- 17041884
TI  - Survival of men with clinically localized prostate cancer treated with
      prostatectomy, brachytherapy, or no definitive treatment: impact of age at
      diagnosis.
AB  - BACKGROUND: The optimal treatment for men with early stage prostate cancer
      remains undefined. Survival of such patients after surgery, brachytherapy, or no
      definitive therapy was investigated specifically to determine the impact of age
      at diagnosis. METHODS: In all, 60,290 men diagnosed with organ-confined, low and
      moderate grade prostate cancer between 1988 and 2002 were retrospectively
      identified from centers participating in the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) Program. Prostate cancer
      specific mortality (PCSM) and any-cause mortality (ACM) were determined. Outcomes
      for patients treated by brachytherapy, surgery, or receiving no definitive
      treatment were compared using the Wilcoxon test, stratified by T-stage and grade,
      and using multivariate analysis. RESULTS: The median follow-up time was 46 months
      (range, 0-189 months). For men under age 60 at diagnosis, PCSM at 10 years was
      1.3%, 0.5%, and 3.7% for surgery, brachytherapy, and no definitive therapy,
      respectively. For men age 60 and older the PCSM was 3.8%, 5.3%, and 8.4%,
      respectively. On univariate and multivariate analysis, surgery and brachytherapy
      resulted in statistically equivalent PCSM and ACM, and both had a significantly
      lower PCSM and ACM versus no definitive therapy. CONCLUSIONS: A better survival
      was observed in men treated with a definitive therapy. The magnitude of the
      benefit on PCSM or ACM was similar for both definitive therapies irrespective of
      age.

PMID- 17041885
TI  - Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant
      mesothelioma cells.
AB  - BACKGROUND: The over-expression of the ephrin-A1 ligand receptor EphA2 is
      associated with the growth and metastatic potential of tumors. Although EphA2 is
      expressed in a variety of tumors, its expression and function in malignant
      mesothelioma (MM) remain unknown. The authors hypothesized that expression of the
      receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic
      migration of MM. They also hypothesized that silencing EphA2 expression by using
      small-interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs
      and induces apoptosis in MMCs. METHODS: The expression of EphA2 in MMCs and in
      normal pleural mesothelial cells (PMCs) was studied by using real-time
      quantitative polymerase chain reaction analysis and Western blot analysis. The
      growth of MMCs was determined with the WST-1 cell-proliferation assay. The
      haptotactic migration of MMCs and PMCs was determined with a Boyden chamber
      assay. Expression of caspases was determined with calorimetric assays. RESULTS:
      The results demonstrated that silencing the receptor EphA2 by siRNA significantly
      reduced the proliferation and haptotactic migration of MMCs compared with
      controls. Over-expression of EphA2 with plasmid pcDNA/EphA2 enhanced the
      proliferation and haptotaxis of MMCs significantly. Knocking down EphA2
      expression initiated caspase-9-mediated apoptosis in MMCs. CONCLUSIONS: The
      current results suggested that constitutive expression of EphA2 may contribute to
      the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective
      therapeutic target in patients with mesothelioma. Silencing the receptor EphA2
      gene is a novel approach for the containment of growth and migration of tumor in
      patients with malignant mesothelioma.

PMID- 17041886
TI  - Comparison of mRNA abundance quantified by gene expression profiling and
      percentage of positive cells using immunophenotyping for diagnostic antigens in
      acute and chronic leukemias.
AB  - BACKGROUND: Microarray analysis is considered a future diagnostic tool in
      leukemias. Whereas data accumulate on specific gene expression patterns in
      biologically defined leukemia entities, data on the correlation between flow
      cytometrically determined protein expression, which are essential in the
      diagnostic setting today, and microarray results are limited. METHODS: The
      results obtained by microarray analysis were compared using the Affymetrix
      GeneChip HG-U133 system in parallel with flow cytometric findings of 36 relevant
      targets in 814 patients with newly diagnosed acute and chronic leukemias as well
      as in normal bone marrow samples. RESULTS: In a total of 21,581 individual
      comparisons between signal intensities obtained by microarray analysis and
      percentages of positive cell as determined by flow cytometry, coefficients of
      correlation in the range of 0.171 to 0.807 were obtained. In particular, the
      degree of correlation was high in the following genes critical in the diagnostic
      setting: CD4, CD8, CD13 (ANPEP), CD33, CD23 (FCER2), CD64 (FCGR1A), CD117 (KIT),
      CD34, MPO, CD20 (MS4A1), CD7 (range of r, 0.589-0.807). CONCLUSIONS: The present
      data prove the high degree of correlation between findings obtained by microarray
      analysis and flow cytometry. They are in favor of a future application of the
      microarray technology as a robust diagnostic tool in leukemias.

PMID- 17041887
TI  - Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we
      establish a minimum number of lymph nodes that should be removed?
AB  - BACKGROUND: The number of lymph nodes (LNs) removed during radical cystectomy
      (RC) for transitional cell carcinoma (TCC) of the bladder affects overall and
      disease-specific survival, but no consensus exists regarding the minimum number
      of LNs that should be removed. The goal of the current study was to determine if
      a threshold number of nodes exists, above which taking additional LNs has no
      clinical benefit. METHODS: A total of 1121 patients were identified who underwent
      RC for clinically localized TCC of the bladder between January 1990 and April
      2004. To determine the relation of LNs removal and overall survival, a Cox
      proportional hazards model was used with pathologic stage, age, and comorbidity
      as covariates. A dose-response curve, adjusted for covariates, was modeled to
      assess the impact of an increasing number of LNs removed on overall survival.
      RESULTS: A median of 9 LNs were removed (range, 0-53 LNs). In multivariable
      analysis, all covariates (number of LNs removed, age, stage of disease, and
      comorbidity) were found to be predictive of survival. The dose-response curve for
      number of LNs versus survival revealed that, when adjusted for covariates, the
      probability of survival did not plateau but instead continued to rise as the
      number of LNs removed increased. CONCLUSIONS: No evidence was found that a
      minimum number of LNs is sufficient for optimizing bladder cancer outcomes when a
      limited or extended pelvic LN dissection is performed during RC. Instead, the
      probability of survival continues to rise as the number of LNs removed increases.
      This study supports a more extended LN dissection at the time of RC, and
      highlights the challenges of interpreting retrospective LN dissection data.

PMID- 17041888
TI  - Cotreatment with a novel phosphoinositide analogue inhibitor and carmustine
      enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas.
AB  - BACKGROUND: Heightened activity of the AKT signaling pathway is prominent in
      malignant gliomas and has been suggested to play a role in treatment resistance.
      Selective targeting of AKT, therefore, may increase chemosensitivity. Recently, a
      novel class of AKT-selective inhibitors has been described, including SH-6, a
      phosphatidylinositol analogue. METHODS: The effects of SH-6 on AKT signaling were
      tested in glioma cells, and the putative role of AKT signaling in chemoresistance
      was tested by attenuating AKT signaling pharmacologically and genetically. The
      initial characterization of SH-6 included treatment of glioma cells with
      increasing doses of SH-6 (0.30-30 microM) and examining the effects on AKT
      signaling proteins by Western blot analyses and in kinase assays with
      immunoprecipitated AKT1. Dose-response studies with SH-6 administered to glioma
      cell lines were performed using a luminescent cell-viability assay (0.1-30
      microM). Studies examining the effect of carmustine, either alone or in
      combination with either the phosphatidylinositol 3-kinase inhibitor LY294002 or
      SH-6, were performed by cell viability assays and clonogenic survival assays. The
      effect of carmustine on AKT activity as a response to treatment also was
      examined. Caspase assays were used to examine the potential role of apoptosis in
      SH-6/ carmustine -elicited cell death. Finally, the induction of a dominant
      negative AKT1 transgene was used in combination with carmustine to demonstrate
      the role of AKT1 in carmustine chemoresistance. RESULTS: Serum-stimulated
      phosphorylation of AKT1 was inhibited by SH-6 at doses > or =10 microM (>70%
      decrease in Threonine 308 and Serine 473 phosphorylation of AKT1). In adenosine
      triphosphate assays, 72 hours of treatment with SH-6 led to 50% lethal doses near
      10 microM for 2 cell lines tested. SH-6 enhancement of carmustine-mediated cell
      death led to synergistic increases in Caspase 3/Capsase 7 activity, implicating
      apoptosis as the cell death mechanism. In clonogenic assays, SH-6 cotreatment
      with carmustine significantly decreased the number of colonies at 10 microM (P <
      .05) compared with carmustine alone. No decrease was observed in cells that were
      treated with SH-6 alone (10 microM). LY294002 (10 microM) was also able to
      enhance the effects of carmustine significantly in both cell lines. CONCLUSIONS:
      In the current study, the authors characterized the efficacy of a new class of
      adjuvant chemotherapeutics that show promise in enhancing the efficacy of
      standard chemotherapy regimens in gliomas.

PMID- 17041889
TI  - Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice
      mutation in PKP2.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic disorder resulting
      in fibro-fatty replacement of right ventricular myocytes and consequent
      ventricular arrhythmias. Heterozygous mutations in PKP2 encoding plakophilin-2
      have previously been reported to cause dominant ARVD with reduced penetrance. We
      report the first case of recessive ARVD caused by mutations in PKP2. Candidate
      gene analysis in a typical proband with this disorder identified a novel
      homozygous mutation in PKP2 (c.[2484C>T]+[2484C>T]), which is predicted to be
      translationally silent (p.Gly828). Analysis of the proband's mRNA, however, shows
      that this mutation causes predominantly cryptic splicing, with a 7-nucleotide
      deletion in exon 12. The ensuing frame shift disrupts the last 54 amino acids of
      plakophilin-2 and extends the open reading frame by 145 nucleotides (48 amino
      acids) into the 3' untranslated region. Haplotype analysis demonstrates the
      absence of remote consanguinity. Heterozygous family members produce
      approximately 60% of properly spliced PKP2 and do not have manifestations of
      ARVD. Further analysis of PKP2 mRNA sequence revealed two additional
      alternatively spliced transcripts. The possibility of cryptic or alternative
      splicing should be considered with identification of apparently synonymous
      nucleotide substitutions in this gene.

PMID- 17041890
TI  - Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in
      Zellweger spectrum patients.
AB  - Mutations in each of the 13 identified human PEX genes are known to cause a
      peroxisomal biogenesis defect (PBD). Affected patients can be divided into two
      broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of
      PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The
      clinical continuum of Zellweger spectrum patients extends from Zellweger syndrome
      (ZS) as the prototype and the most severe entity of this group to neonatal
      adrenoleukodystrophy (NALD) as an intermediate form and infantile Refsum (IRD)
      disease as the mildest variant. Characteristic features of ZS patients are
      dysmorphic features, severe neurological impairment, liver dysfunction, and eye
      and skeletal abnormalities. Similar but less severe clinical signs are seen in
      patients with NALD and IRD. In this study ten clinically and/or biochemically
      well-characterized patients with classical ZS were investigated for defects in
      all known human PEX genes. We identified two novel mutations in PEX2 (official
      symbol, PXMP3), two novel mutations in PEX6, two novel mutations in PEX10, one
      novel mutation in PEX12, and one novel mutation in PEX13.

PMID- 17041891
TI  - A new genetic isolate with a unique phenotype of syndromic oculocutaneous
      albinism: clinical, molecular, and cellular characteristics.
AB  - An extended, highly consanguineous Israeli Bedouin family with at least 20
      individuals exhibiting a unique phenotype of oculocutaneous albinism (OCA) was
      identified. All known OCA genes were excluded in this family. Electron
      microscopic analysis of platelets revealed absence of dense bodies, suggesting a
      diagnosis of Hermansky-Pudlak syndrome (HPS). HPS is a rare autosomal recessive
      disorder of lysosome-related organelle biogenesis, clinically characterized by
      OCA and platelet dysfunction, sometimes accompanied by other systemic
      pathologies. All human HPS genes (HPS1-8) and five genes corresponding to murine
      HPS models were evaluated. Haplotype analysis and homozygosity mapping of the HPS
      loci revealed linkage to chromosome 10 in the studied family. Subsequently, a
      novel insertion mutation, c.1066-1067insG was identified in HPS6. Most frameshift
      mutations generating premature termination codon cause mRNA nonsense mediated
      decay (NMD), while intronless genes like HPS6 are usually not monitored by NMD.
      Expression analysis revealed no mRNA decay in patient's fibroblasts, hence
      truncated protein is most probably produced. Confocal microscopy revealed
      abnormal distribution of LAMP-3 (lysosomal associated membrane protein-3) in
      fibroblasts from the patients, indicating abnormal trafficking of lysosomal
      lineage organelles. So far, a single HPS-6 patient phenotypically similar to HPS
      3 and HPS-5 has been identified. The HPS-6 phenotype in the studied family is
      unique since it resembles OCA and not HPS. Therefore, our finding broadens the
      phenotypic definition of HPS. Two major genetic isolates of HPS-1 and HPS-3
      patients were previously diagnosed in Puerto Rico. The extended Bedouin family is
      the largest isolate of non-Puerto Rican HPS patients.

PMID- 17041892
TI  - The Wnt/beta-catenin pathway: master regulator of liver zonation?
AB  - The liver contains two systems for the removal of ammonia - the urea cycle and
      the enzyme glutamine synthetase. These systems are expressed in a complementary
      fashion in two distinct populations of hepatocytes, referred to as periportal and
      perivenous cells. One of the unresolved problems in hepatology has been to
      elucidate the molecular mechanisms responsible for induction and maintenance of
      the cellular heterogeneity for ammonia detoxification. There is now a potential
      molecular explanation for the zonation of the urea cycle and glutamine synthetase
      based on the Wnt/beta-catenin pathway.

PMID- 17041894
TI  - DiGeorge syndrome and pharyngeal apparatus development.
AB  - DiGeorge syndrome is the most frequent microdeletion syndrome in humans, and is
      characterized by cardiovascular, thymic and parathyroid, and craniofacial
      anomalies. The underlying cause is disturbed formation of the pharyngeal
      apparatus, a transient structure present during vertebrate development that gives
      rise to endocrine glands, craniofacial tissue, and the cardiac outflow tract. The
      pharyngeal apparatus is composed of derivatives of ectoderm, endoderm, mesoderm
      and the neural crest. Thus, complex interactions between cell types from
      different origins have to be orchestrated in the correct spatiotemporal manner to
      establish proper formation of the pharyngeal system. The analysis of engineered
      mouse mutants developing a phenotype resembling DiGeorge syndrome has revealed
      genes and signalling pathways crucial for this process. Intriguingly, these mouse
      models reveal that interference with either of two distinct phases of pharyngeal
      apparatus development can contribute to the aetiology of DiGeorge syndrome.

PMID- 17041893
TI  - Measurement of phosphorus content in normal and osteomalacic rabbit bone by solid
      state 3D radial imaging.
AB  - In osteomalacia decreased mineralization reduces the stiffness and static
      strength of bone. We hypothesized that hypomineralization in osteomalacic bone
      could be quantified by solid-state (31)P magnetic resonance imaging (SS-MRI).
      Hypomineralization was measured with a 3D radial imaging technique at 162 MHz
      (9.4T) in rabbit cortical bone of hypophosphatemic (HY) and normophosphatemic
      (NO) animals. The results were compared with those obtained by quantitative micro
      CT (micro-CT) and (31)P solution NMR. 3D images of 277 microm isotropic voxel
      size were obtained in 1.7 hr with SNR approximately 9. Mineral content was lower
      in the HY relative to the NO group (SS-MRI: 9.48 +/- 0.4 vs. 11.15 +/- 0.31
      phosphorus wet wt %, P < 0.0001; micro-CT: 1114.6 +/- 28.3 vs. 1175.7 +/- 23.5 mg
      mineral/cm(3); P = 0.003). T(1) was shorter in the HY group (47.2 +/- 3.5 vs.
      54.1 +/- 2.7 s, P = 0.004), which suggests that relaxation occurs via a dipole
      dipole (DD) mechanism involving exchangeable water protons, which are more
      prevalent in bone from osteomalacic animals.

PMID- 17041895
TI  - Genome-wide prediction of genetic interactions in a metazoan.
AB  - Genetic interactions provide information about genes and processes with
      overlapping functions in biological systems. For Saccharomyces cerevisiae,
      computational integration of multiple types of functional genomic data is used to
      generate genome-wide predictions of genetic interactions. However, this
      methodology cannot be applied to the vastly more complex genome of metazoans, and
      only recently has the first metazoan genome-wide prediction of genetic
      interactions been reported. The prediction for Caenorhabditis elegans was
      generated by computationally integrating functional genomic data from S.
      cerevisiae, C. elegans and Drosophila melanogaster. This achievement is an
      important step toward system-level understanding of biological systems and human
      diseases.

PMID- 17041896
TI  - Identification of novel mutations in the human ornithine transcarbamylase (OTC)
      gene of Korean patients with OTC deficiency and transient expression of the
      mutant proteins in vitro.
AB  - The urea cycle plays key roles to prevent the accumulation of toxic nitrogenous
      compound and synthesize arginine de novo. Ornithine transcarbamylase (OTC)
      deficiency is the most common inborn error of urea cycle, which is inherited in
      an X-linked manner. This study was undertaken to characterize molecular defects
      in Korean patients with OTC deficiency. With direct sequence analysis of OTC gene
      of 26 unrelated Korean patients with OTC deficiency, 23 different mutations were
      identified. Among these mutations, eleven were novel mutations. The novel
      mutations were p.Leu9X, p.Arg26Pro, p.Gly100Arg, p.Met205Thr, p.Lys221Asn,
      p.Asp249Gly, p.Phe281Ser, p.Val323Met, c.571delC, c.853delC, and c.796-805del.
      All the novel mutations in this study were tested in 100 normal alleles. In vitro
      expression study of some of novel missense mutations elucidated the correlation
      of genotype and phenotype of the OTC deficiency.

PMID- 17041897
TI  - Deficient membrane integration of the novel p.N14D-GJB2 mutant associated with
      non-syndromic hearing impairment.
AB  - Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26
      (Cx26), have been established as the major cause of hereditary, non-syndromic
      hearing impairment (HI). We report here the identification of a novel point
      mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the
      c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI.
      The mother who carried one wildtype and a p.N14D allele displayed normal hearing.
      The mutation leads to substitution of the neutral amino acid asparagine (N) by
      the negatively charged aspartic acid (D) at amino acid number 14, a position that
      is conserved among Cx26 of different organisms and among many other connexin
      isoforms. To investigate the impact of this mutation on protein function, Cx26
      activity was measured by depolarization activated hemichannel conductance in non
      coupled Xenopus laevis oocytes. Oocytes injected with the p.N14D mutant cRNA
      showed strongly reduced currents compared to wildtype. Coinjection of wildtype
      and mutant cRNA at equimolar levels restored the conductive properties supporting
      the recessive character of this mutation. Total Cx26 protein expression and cell
      surface abundance examined by western blotting and by quantitative immunoassays
      revealed that the hemichannel was properly synthesized but not integrated into
      the plasma membrane. In this study we have shown that the GJB2 mutation p.N14D is
      associated with recessively inherited HI and exhibits a defective phenotype due
      to diminished expression at the cell surface.

PMID- 17041898
TI  - Reactive oxygen species as signals that modulate plant stress responses and
      programmed cell death.
AB  - Reactive oxygen species (ROS) are known as toxic metabolic products in plants and
      other aerobic organisms. An elaborate and highly redundant plant ROS network,
      composed of antioxidant enzymes, antioxidants and ROS-producing enzymes, is
      responsible for maintaining ROS levels under tight control. This allows ROS to
      serve as signaling molecules that coordinate an astonishing range of diverse
      plant processes. The specificity of the biological response to ROS depends on the
      chemical identity of ROS, intensity of the signal, sites of production, plant
      developmental stage, previous stresses encountered and interactions with other
      signaling molecules such as nitric oxide, lipid messengers and plant hormones.
      Although many components of the ROS signaling network have recently been
      identified, the challenge remains to understand how ROS-derived signals are
      integrated to eventually regulate such biological processes as plant growth,
      development, stress adaptation and programmed cell death.

PMID- 17041899
TI  - Red cell glucose phosphate isomerase (GPI): a molecular study of three novel
      mutations associated with hereditary nonspherocytic hemolytic anemia.
AB  - Molecular characteristics of red blood cell (RBC) glucose phosphate isomerase
      (GPI) deficiency are described in two Spanish patients with chronic
      nonspherocytic hemolytic anemia. One patient, with residual GPI activity in RBCs
      of around 7% (GPI-Catalonia), is homozygous for the missense mutation c.1648A>G
      (p.Lys550Glu) in exon 18. The other patient, with residual activity in RBCs of
      around 20% (GPI-Barcelona), was found to be a compound heterozygote for two
      different missense mutations: c.341A>T (p.Asp113Val) in exon 4 and c.663T>G
      (p.Asn220Lys) in exon 7. Molecular modeling using the human crystal structure of
      GPI as a model was performed to determine how these mutations could affect enzyme
      structure and function.

PMID- 17041900
TI  - On the dynamic nature of positional information.
AB  - Morphogenetic fields are among the most fundamental concepts of embryology.
      However, they are also among the most ill-defined, since they consist of dynamic
      regulatory processes whose exact nature remains elusive. In order to achieve a
      more rigorous definition of a developmental field, Lewis Wolpert introduced the
      concept of positional information illustrated by his French Flag model. Here we
      argue that Wolpert's positional information - a static coordinate system defining
      a field - lacks essential properties of the original field concept. We show how
      data-driven mathematical modeling approaches now enable us to study regulatory
      processes in a way that is qualitatively different from our previous level of
      understanding. As an example, we review our recent analysis of segmentation gene
      expression in the blastoderm embryo of the fruit fly Drosophila melanogaster.
      Based on this analysis, we propose a revised French Flag, which incorporates the
      dynamic, feedback-driven nature of pattern formation in the Drosophila
      blastoderm.

PMID- 17041901
TI  - On the origins of morphological disparity and its diverse developmental bases.
AB  - It has been repeatedly claimed that morphological novelties are an unresolved
      problem in evolutionary theory. Several definitions of novelty exist but most
      emphasize that novelties imply qualitative changes on the phenotype and not the
      quantitative gradual changes favored in the neo-Darwinian approach to
      evolutionary theory. This article discusses how the concept of novelty is used to
      describe aspects of morphological evolution that are not satisfactorily explained
      under the modern synthesis. In this article, it is suggested that there is a
      repertoire of morphological changes rather than two discrete qualitatively
      different types of morphological change. How these different types of
      morphological changes can be understood from the diversity of developmental
      mechanisms existing in animal development is explored. Specifically, it is
      proposed that animal morphology and its variation can be understood from the
      spatial patterns produced by a set of basic developmental mechanisms and their
      combination. Some specific examples of these kinds of morphologic changes are
      explained.

PMID- 17041902
TI  - Meiosis and sex: potent weapons in the competition between early eukaryotes and
      prokaryotes.
AB  - The earliest eukaryote species almost certainly evolved in an environment
      dominated by numerous prokaryotic species. If the first eukaryotic cells were
      larger and grew more slowly than their prokaryotic neighbours, they might well
      have been at a competitive disadvantage. It is proposed here that the early
      evolution of meiosis, with its capacity for generating new favourable gene
      combinations, might have served to offset any such competitive disadvantages.
      Meiosis and sex could have arisen in an asexually reproducing species and formed
      a clonal population.

PMID- 17041903
TI  - Detection of ultrarare somatic mutation in the human TP53 gene by bidirectional
      pyrophosphorolysis-activated polymerization allele-specific amplification.
AB  - The detection of ultra-rare mutation in the presence of excess amounts of normal
      genomic DNA is highly advantageous in a number of circumstances, including: 1)
      identification of minimal residual disease for improved cancer chemotherapy; 2)
      measurement of mutation load to assess environmental mutagen exposure or
      endogenous DNA repair; and 3) prenatal diagnosis of paternally-derived mutations
      within fetal cells in the maternal circulation. Bidirectional pyrophosphorolysis
      activated polymerization allele-specific amplification (Bi-PAP-A) utilizes two
      opposing 3'-terminal blocked oligonucleotides (P(*)s) with 1 nucleotide overlap
      at their 3' termini. The selectivity of Bi-PAP-A derives from the serial coupling
      of pyrophosphorolysis and DNA polymerization. A total of 13 Bi-PAP-A assays were
      developed and validated for the human p53 gene (TP53). The sensitivity and
      specificity of each assay were determined with mutated and wild-type DNA
      templates, respectively. Bi-PAP-A has a sensitivity of one molecule for most
      assays and a selectivity (sensitivity:specificity) greater than 1:10(7)-1:10(9)
      for four of all six mutation types. Four assays with high selectivity were used
      to detect rare somatic mutations in blood white cells. The silent g.13147C>G
      (p.R156) mutation was present at an estimated frequency of 1.1 x 10(-7). The
      g.14523A>T (p.E285V), g.14487G>C (p.R273P), and g.14060G>C (p.G245R) mutations
      were undetectable with frequencies less than 2.0 x 10(-8). We conclude that Bi
      PAP-A is a general and rapid method for detecting ultra-rare mutations.

PMID- 17041904
TI  - Autophagy in neuronal cell loss: a road to death.
AB  - The regulation of ageing has been extensively studied in divergent animal model
      systems including worms, flies and mice. However, little is known about the
      cellular pathways that mediate the death of these organisms. Analysing major
      cellular changes in the ageing nematode Caenorhabditis elegans has revealed a
      gradual, progressive deterioration of different tissues except for the nervous
      system, which remarkably preserves its integrity even in advanced old age. In
      addition, genetic data have shown that, in C. elegans and in the fruit fly
      Drosophila melanogaster, lifespan is controlled by signals derived from neurons
      and acting throughout adulthood. Organismal death thus seems to be a consequence
      of the decline of specific neurons. Accumulating evidence demonstrates that late
      onset of neuronal cell loss generally occurs via autophagy, a process in which
      eukaryotic cells self-digest parts of their contents during development or to
      survive starvation. Here we suggest that overactivation of autophagy in the cells
      of the nervous system is the eventual cause of "physiological" death.

PMID- 17041905
TI  - mRNPs take shape by CLIPPING and PAIRING.
AB  - The interaction of RNA-binding proteins (RBPs) with RNA is a crucial aspect of
      normal cellular metabolism. Yet, the diverse number of RBPs and RNA motifs to
      which they bind, the wide range of interaction strengths and the fact that RBPs
      associate in dynamic complexes have made it challenging to determine whether a
      particular RNA-binding protein binds a particular RNA. Recent work by three
      different laboratories has led to the development of new tools to query such
      interactions in the more physiological environs of cultured cells. The use of
      these methods has led to insights into (1) the networks of RNAs regulated by a
      particular protein, (2) the identification of new protein partners within
      messenger ribonucleoprotein particles and (3) the flux of RNA-binding proteins on
      an mRNA throughout its lifecycle. Here, I examine these new methods and discuss
      their relative strengths and current limitations.

PMID- 17041906
TI  - Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point
      mutations and molecular basis for BMD with nonsense and frameshift mutations in
      the DMD gene.
AB  - Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements,
      such as deletions or duplications involving an entire exon or more, are involved
      in about 70% of dystrophinopathies. In the remaining 30% a variety of point
      mutations or "small" mutations are suspected. Due to their diversity and to the
      large size and complexity of the DMD gene, these point mutations are difficult to
      detect. To overcome this diagnostic issue, we developed and optimized a routine
      muscle biopsy-based diagnostic strategy. The mutation detection rate is almost as
      high as 100% and mutations were identified in all patients for whom the diagnosis
      of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further
      supported by the detection on Western blot of quantitative and/or qualitative
      dystrophin protein abnormalities. Here we report a total of 124 small mutations
      including 11 nonsense and frameshift mutations detected in BMD patients. In
      addition to a comprehensive assessment of muscular phenotypes that takes into
      account consequences of mutations on the expression of the dystrophin mRNA and
      protein, we provide and discuss genomic, mRNA, and protein data that pinpoint
      molecular mechanisms underlying BMD phenotypes associated with nonsense and
      frameshift mutations.

PMID- 17041907
TI  - Fourth international symposium on the biology of vertebrate sex determination.

PMID- 17041908
TI  - Recruitment pharmacophore for interleukin 5 receptor alpha antagonism.
AB  - Interleukin-5 receptor alpha is a therapeutic target for hypereosinophilic
      diseases including allergic inflammations and asthma. The cyclic peptide AF17121
      (Ac-VDE[CWRIIASHTWFC]AEE-CONH(2)) has been identified as a submicromolar
      inhibitor of interleukin 5 (IL5)-interleukin 5 receptor alpha (IL5Ralpha)
      interaction from a random peptide screen. However, this inhibitor has limitations
      as a drug lead because of its relatively large size. We used chemical synthesis
      of peptides with natural and non-natural amino acids along with kinetic binding
      and cell proliferation competition assays to expand definition of structural
      elements in the peptide that are important for receptor antagonism and to
      elucidate the underlying pharmacophore. We found that the specific steric array
      of hydrogen bonding groups in the Arg 6 guanido side chain is critical for
      receptor inhibition. We also investigated noncharged structural elements in
      AF17121. Screening a set of five hydrophobic residues showed that peptide
      function is strongly sensitive to variations in several of these residues, most
      prominently Ile 7 and Trp 13. We postulate that presentation of charged, hydrogen
      bonding and hydrophobic structural elements within the disulfide-constrained
      peptide drives IL5Ralpha recruitment by AF17121. We hypothesize from these
      results and previous receptor mutagenesis studies that Arg 6 recruitment of
      IL5Ralpha occurs through hydrogen bonding as well as charge-charge interactions
      with Asp 55 in site one of domain 1 of IL5Ralpha, and that this interaction is
      complemented by additional charged and hydrophobic interactions around the Asp 55
      locus. Scaffolding a limited set of structural elements in the inhibitor
      pharmacophore may be useful for small molecule antagonist design inspired by the
      peptide.

PMID- 17041909
TI  - Human biology: an ever-expanding subject.

PMID- 17041910
TI  - Multiexon skipping leading to an artificial DMD protein lacking amino acids from
      exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular
      dystrophy.
AB  - Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show
      intragenic deletions ranging from one to several exons of the DMD gene and
      leading to a premature stop codon. Other deletions that maintain the
      translational reading frame of the gene result in the milder Becker muscular
      dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD
      phenotype into a BMD phenotype appeared as a new treatment strategy with the
      development of antisense oligonucleotides technology, which is able to induce an
      exon skipping at the pre-mRNA level in order to restore an open reading frame.
      Because the DMD gene contains 79 exons, thousands of potential transcripts could
      be produced by exon skipping and should be investigated. The conventional
      approach considers skipping of a single exon. Here we report the comparison of
      single- and multiple-exon skipping strategies based on bioinformatic analysis. By
      using the Universal Mutation Database (UMD)-DMD, we predict that an optimal
      multiexon skipping leading to the del45-55 artificial dystrophin (c.6439_8217del)
      could transform the DMD phenotype into the asymptomatic or mild BMD phenotype.
      This multiple-exon skipping could theoretically rescue up to 63% of DMD patients
      with a deletion, while the optimal monoskipping of exon 51 would rescue only 16%
      of patients.

PMID- 17041911
TI  - Advanced three-dimensional tailored RF pulse for signal recovery in T2*-weighted
      functional magnetic resonance imaging.
AB  - T(2) (*)-weighted functional MR images are plagued by signal loss artifacts
      caused by susceptibility-induced through-plane dephasing. We present major
      advances to the original three-dimensional tailored RF (3DTRF) pulse method that
      pre-compensates the dephasing using three-dimensional selective excitation. The
      proposed 3DTRF pulses are designed iteratively with off-resonance incorporation
      and with a novel echo-volumar trajectory that frequency-encodes in z and phase
      encodes in x,y. We also propose a computational scheme to accelerate the pulse
      design process. We demonstrate effective signal recovery in a 5-mm slice in both
      phantom and inferior brain, using 3DTRF pulses that are only 15.4 ms long.
      Compared to the original method, the new approach leads to significantly reduced
      pulse length and enhancement in slice selectivity. 3D images of the slice volume
      confirm fidelity of the excited phase pattern and slice profile.

PMID- 17041912
TI  - The effect of zoledronic acid incorporated in a poly(D,L-lactide) implant coating
      on osteoblasts in vitro.
AB  - Bisphosphonates such as zoledronic acid (ZOL) are used in diseases associated
      with osteoclast-mediated bone loss. However, their antiresorptive activity is
      partly due to their effect on osteoblasts. Local application might increase the
      therapeutical fence and their local efficiency and reduce systemic side effects.
      Aim of the study was to investigate the effect of ZOL on human osteoblasts like
      cells in vitro with special focus on the synthesis of factors mediating
      osteoclast differentiation (RANKL, OPG). ZOL was incorporated in an implant
      coating based on poly(D,L-lactide) (PDLLA) in different concentrations (10-150
      microM). Control groups were treated with uncoated implants, PDLLA-coated
      implants, and ZOL pure substance in corresponding concentrations. After an
      experimental period of 144 h, primary human osteoblasts were stained with alamar
      blue and cell viability was measured. Procollagen I synthesis, osteoprotegerin
      (OPG) secretion, and soluble receptor activator of nuclear factor-kappaB ligand
      (sRANKL) were analyzed. Results showed that cell viability was not affected when
      treated with doses equivalent up to 100 microM ZOL-coated implants (ZOL-CI).
      Procollagen I synthesis was highest when treated with 50 microM ZOL-CI. OPG
      increased significantly in the 10 microM ZOL-CI group, whereas sRANKL decreased
      significantly with different concentrations of ZOL-CI. Higher concentrations or
      exposure to the pure substance showed a decrease in cell viability, collagen I,
      OPG, and sRANKL synthesis. In conclusion, exposure to specific concentrations of
      ZOL-CI showed a beneficial effect on osteoblast differentiation and protein
      synthesis without influencing their proliferation. Changes in sRANKL and OPG
      production may contribute to the inhibition of osteoclastic bone resorption. This
      local antiresorptive effect might be clinically useful in osseous implant
      integration and fracture healing.

PMID- 17041913
TI  - Effects of collagen fiber orientation on the response of biologically derived
      soft tissue biomaterials to cyclic loading.
AB  - In the present study, the effects of initial collagen fiber orientation on the
      medium-term (up to 50 x 10(6) cycles) fatigue response of heart valve soft tissue
      biomaterials was investigated. Glutaraldehyde treated bovine pericardium (GLBP),
      preselected for uniform structure and collagen fiber orientation, was used as the
      representative heart valve biomaterial. Using specialized instrumentation, GLBP
      specimens were subjected to cyclic tensile loading to maximum stress levels of
      500 +/- 50 kPa at a frequency of 22 Hz. Two sample groups were examined, one with
      the preferred collagen fiber direction parallel (PD) and perpendicular (XD) to
      the direction of applied strain. The primary findings indicated that GLBP fatigue
      response was highly sensitive to the direction of loading with respect to fiber
      orientation. Specifically, when loading perpendicular to the preferred collagen
      fiber orientation, fiber reorientation is the dominant mechanism. In contrast,
      when loaded parallel to the preferred fiber direction a reduction in both
      collagen fiber crimp and fiber reorientation occurred. Moreover, alterations in
      the degree and direction of mechanical anisotropy can be inducted by cyclic
      loading when specimens are loaded perpendicular to the preferred fiber direction.
      Fourier Transform Infrared Spectroscopy (FT-IR) results indicate that molecular
      level damage to collagen occurs in both groups after only 20 x 10(6) cycles.
      Taken as a whole, the results of this study suggest that initial collagen
      orientation plays a critical role in bioprosthetic heart valve biomaterial
      fatigue response.

PMID- 17041914
TI  - Rumination in posttraumatic stress disorder.
AB  - Recent studies have shown that rumination is a powerful predictor of persistent
      posttraumatic stress disorder (PTSD). However, to date, the mechanisms by which
      rumination maintains PTSD symptoms are little understood. Two studies of assault
      survivors, a cross-sectional (N = 81) and a 6-month prospective longitudinal
      study (N = 73), examined several facets of ruminative thinking to establish which
      aspects of rumination provide the link to PTSD. The current investigation showed
      that rumination is not only used as a strategy to cope with intrusive memories
      but it also triggers such memories. Certain characteristics of rumination, such
      as compulsion to continue ruminating, occurrence of unproductive thoughts, and
      "why" and "what if" type questions, as well as negative emotions before and after
      rumination, were significantly associated with PTSD, concurrently and
      prospectively. These characteristics explained significantly more variance in
      PTSD severity than the mere presence of rumination, thereby indicating that not
      all ways of ruminative thinking are equally maladaptive.

PMID- 17041915
TI  - Association of cigarette smoking and depressive symptoms in a forensic
      population.
AB  - The link between mental health issues and smoking has been an important area of
      investigation. However, little is known about this association in a general
      adult, male forensic population. The aim of this study was to identify
      demographic and clinical (depression and anxiety) variables that predict smoking
      in a forensic population. A large cohort of 353 inmates in a high-security prison
      underwent a psychiatric interview, including administration of the Montgomery
      Asberg Rating Scale for Depression (MADRS) and Hamilton's Rating Scale for
      Anxiety (HAM-A). Multiple regression analysis suggested that younger age and
      higher depression scores might predict the amount of daily smoking in this
      population. In contrast, anxiety symptoms were not an independent predictor for
      smoking in our study. These findings support the need for additional research to
      focus on those factors associated with smoking in forensic populations.
      Psychiatric screening for younger male individuals in forensic settings and
      targeted cognitive-behavioral interventions to treat depressed smokers may
      ameliorate the smoking abstinence rate in prisons.

PMID- 17041916
TI  - Sieving functional morphology of the gill raker feeding apparatus of atlantic
      menhaden.
AB  - Menhaden occupy an important position in estuarine food webs, thus the rate
      processes associated with their feeding are critical to the ecosystem management
      of fishery and ecological resources. Atlantic menhaden feed on a wide range of
      plankton, the size and food quality of which change ontogenetically. We analyzed
      the functional morphology of the menhaden feeding apparatus in a size series of
      menhaden representative of juveniles and the adult migratory stock. The physical
      dimensions of gill arches and rakers increased isometrically with fish length;
      however, branchiospinule spacing, the dimension that forms the sieve apertures of
      the branchial basket, scaled allometrically with fish length. Juvenile menhaden
      from North Carolina have branchiospinule spacings that averaged 12 microm, with
      three arch subsections of average spacing < 10 microm. Spacings did not increase
      with juvenile growth until the first allometric inflection point at approximately
      100 mm fork length (FL). Spacing data for juveniles from other locations suggests
      spacing increases with latitude. Spacings increase with fish length in adults
      until a second inflection at 200 mm FL, after which spacing averages 37 microm.
      These data suggest menhaden juveniles filter smaller plankton with higher
      filtration efficiency than previously considered and that regional recruitment
      may affect adult distribution through foraging preferences.

PMID- 17041917
TI  - Uterine motility in the reptile Anolis carolinensis: interactive effects of
      tension, prostaglandins, calcium, and vasotocin.
AB  - Uteri of Anolis carolinensis exhibited spontaneous rhythmic contractions in
      vitro. Addition of arginine vasotocin (AVT) caused an immediate, strong, tonic
      contraction followed by rhythmic contractions with the same frequency as
      spontaneous contractions but of a greater amplitude. At low tension (1.5 g) the
      AVT-induced tonic contraction was blocked by low dose of indomethacin, suggesting
      that it is influenced by calcium rather than prostaglandins (PGs). An increase in
      tension (from 1.5 to 15 g) reduced the duration of the AVT-induced tonic
      contraction; this stretch-induced decrease was also blocked by indomethacin.
      Stretch also decreased the duration of the rhythmic contractions, but this
      stretch effect was not inhibited by indomethacin. The rest interval between
      rhythmic contractions was decreased by PGF2alpha and PGE2, and indomethacin or
      stretch blocked these PG effects. Indomethacin, AVT, or stretch alone did not
      affect PGF2alpha secretion from AVT-treated uteri. Stretch also reduced PGF2alpha
      secretion from AVT-treated uteri, an effect inhibited by indomethacin.

PMID- 17041918
TI  - Regulation of immunocompetence by different androgen metabolites in a blenny with
      alternative reproductive tactics.
AB  - In Parablennius parvicornis, small reproductive males with relatively low
      expression of secondary sexual characters (M- morphotype) parasite on the
      parental investment of the larger nest-holder males which have fully developed
      secondary sexual characters (M+ morphotype). In comparison with M+ males, M-
      males have relatively low levels of androgens while having high blood cell
      percentages of lymphocytes and antigen responsiveness. Here we test the
      hypothesis that androgens are a causal factor for these differences in
      immunocompetence between morphotypes. After drawing an initial blood sample,
      males received a silastic implant containing either oil only (C), or oil with
      testosterone (T) or 11-ketotestosterone (KT). Males were re-caught 2 weeks later
      for drawing of the final blood sample. KT but not T induced the development of
      secondary sexual characters in M- males. M- males treated with KT showed lower
      swimming activity than the males treated with T or C implants, suggesting that KT
      also mediates behavioral changes in M- males. As expected, blood cell percentages
      of lymphocytes, but not of granulocytes, were higher in M- males than in M+
      males. Overall, lymphocyte percentages increased in the C group which might have
      been a response to the surgery/treatment. In concordance with the hypothesis,
      lymphocyte percentages were suppressed in males treated with T in comparison with
      controls. However, no significant change was found in KT-treated males. This
      suggests that androgens modulate central, morphological and immunological traits
      by partly independent androgen mechanisms in P. parvicornis.

PMID- 17041919
TI  - Structure-activity relationship studies of a series of peptidomimetic ligands for
      alpha(4) beta(1) integrin on Jurkat T-leukemia cells.
AB  - alpha(4)beta(1) integrin is a therapeutic target for inflammation, autoimmune
      diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the
      Nle-D-I motif have been synthesized and their binding affinities (IC(50)) to
      activated alpha(4)beta(1) integrin on Jurkat T-leukemia cells have been
      determined using a cell adhesion assay. One of the 51 ligands, 18, has been
      determined to have an IC(50) of 0.6 nM and has a more than twofold increase of
      binding affinity than the initial lead compound 1. Extensive SAR studies provide
      important information for further ligand optimization, which has served as a
      foundation for studies that ultimately led to identification of a potent ligand
      with an IC(50) of 2 pM.

PMID- 17041920
TI  - Pineal germinoma presenting as anorexia nervosa: Case report and review of the
      literature.
AB  - OBJECTIVE: Tumors of the hypothalamic-pineal region may present with a wide
      variety of symptoms, including disturbed eating. We present a case where such a
      tumor was misdiagnosed as anorexia nervosa. METHOD: We describe a case of pineal
      germinoma invading the hypothalamus, which was initially diagnosed as anorexia
      nervosa. RESULTS: Clinical features included weight loss, vomiting, pyrexia,
      hypernatraemia, and visual disturbance and the typical psychopathology of
      anorexia nervosa was absent. CONCLUSION: Organic disorder should always be
      considered before making a diagnosis of anorexia nervosa, particularly if the
      presentation is atypical.

PMID- 17041921
TI  - Korean Anxiety Sensitivity Index-Revised: its factor structure, reliability, and
      validity in clinical and nonclinical samples.
AB  - The factor structure and convergent and discriminant validity of the Anxiety
      Sensitivity Index-Revised (ASI-R) were examined in a community sample, a student
      sample, and patients with panic disorder in Korea. Results from a confirmatory
      factor analysis (CFA) comparing our data to factor solutions commonly reported as
      representative of European American populations indicated a poor fit. A
      subsequent exploratory factor analysis (EFA) indicated that a four-factor
      solution provided the best fit. Correlations between the ASI-R and anxiety
      measures were moderately high, providing evidence of convergent validity.
      Implications for assessment with Koreans are discussed.

PMID- 17041922
TI  - A prospective study of escitalopram in the treatment of major depressive episodes
      in the presence or absence of anxiety.
AB  - This open, multicenter, prospective study in France assessed the efficacy and
      tolerability of escitalopram in patients with depression, with or without
      comorbid anxiety. Escitalopram was administered over a 12-week treatment period
      to 790 depressed patients, including 482 patients with at least one concomitant
      anxiety disorder. The study was completed by 649 patients. At baseline, the mean
      Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and
      decreased to 12.4 at end point (last observation carried forward [LOCF]). The
      MADRS score decreased by 20.5 points in patients with no anxiety disorder and by
      18.3 points in patients with at least one concomitant anxiety disorder. The mean
      Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which
      decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points
      in patients with no anxiety disorder and by 15.5 points in patients with at least
      one anxiety disorder. Adverse events were reported by 246 patients (31%). The
      most frequent adverse events were nausea in 65 patients (8%) and headache in 38
      patients (5%); 61 patients (8%) discontinued treatment due to adverse events.
      Escitalopram was well tolerated and efficacious in reducing symptoms of
      depression in patients with or without comorbid anxiety over a 12-week treatment
      period.

PMID- 17041923
TI  - A novel G106D alteration of the SDHD gene in a pedigree with familial
      paraganglioma.
AB  - Head and neck paragangliomas are tumors derived from parasympathetic paraganglia.
      Familial cases account for 10% or more of these tumors, and mutations of the
      genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD,
      SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH
      genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that
      include a father with bilateral tumors and his daughter with a malignant left
      carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D
      alteration in exon 4 of the SDHD gene that has not previously been reported to
      date. The tumors of the father expressed biallelic SDHD, but the SDHD expression
      was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and
      the wild-type allele was predominantly suppressed in the metastatic node. These
      results suggest that the missense dysfunction of SDHD prepares neoplastic
      condition and that expressional silencing, particularly of the wild-type allele,
      plays an important role in the malignant transformation of the paragangliomas.
      Our results may lead to a better understanding of this disease and to the
      development of methods for prevention of this disease.

PMID- 17041924
TI  - Friction of total hip replacements with different bearings and loading
      conditions.
AB  - Metal-on-ultra-high molecular weight polyethylene (UHMWPE) total hip replacements
      have been the most popular and clinically successful implants to date. However,
      it is well documented that the wear debris from these prostheses contributes to
      osteolysis and ultimate failure of the prosthesis, hence alternative materials
      have been sought. A range of 28 mm diameter bearings were investigated using a
      hip friction simulator, including conventional material combinations such as
      metal-on-UHWMPE, ceramic-on-ceramic (CoC), and metal-on-metal (MoM), as well as
      novel ceramic-on-metal (CoM) pairings. Studies were performed under different
      swing-phase load and lubricant conditions. The friction factors were lowest in
      the ceramic bearings, with the CoC bearing having the lowest friction factor in
      all conditions. CoM bearings also had low friction factors compared with MoM, and
      the trends were similar to CoC bearings for all test conditions. Increasing swing
      phase load was shown to cause an increase in friction factor in all tests.
      Increased serum concentration resulted in increased friction factor in all
      material combinations, except MoM, where increased serum concentration produced a
      significant reduction in friction factor.

PMID- 17041925
TI  - In vivo performance of antibiotic embedded electrospun PCL membranes for
      prevention of abdominal adhesions.
AB  - The aim of this study was to prepare nonwoven materials from poly(epsilon
      caprolactone) (PCL) and their antibiotic containing forms by electrospinning, so
      as to prevent postsurgery induced abdominal adhesions in rats. epsilon
      Caprolactone was first polymerized by ring-opening polymerization, and then it
      was processed into matrices composed of nanofibers by electrospinning. A model
      antibiotic (Biteral) was embedded within a group of PCL membranes. In the rat
      model, defects on the abdominal walls in the peritoneum were made to induce
      adhesion. The plain or antibiotic embedded PCL membranes were implanted on the
      right side of the abdominal wall. No membrane implantation was made on the left
      side of the abdominal wall that served as control. Macroscopical and histological
      evaluations showed that using these barriers reduces the extent, type, and
      tenacity of adhesion. The antibiotic embedded membranes significantly eliminated
      postsurgery abdominal adhesions, and also improved healing.

PMID- 17041926
TI  - Evaluation of an accelerated aging medium for acrylic bone cement based on
      analysis of nanoindentation measurements on laboratory-prepared and retrieved
      specimens.
AB  - The thrust of the study was a critical evaluation of the efficacy of a medium
      (30% v/v H(2)O(2), at 60 degrees C) that has been suggested in a literature
      report as being suitable for simulating the oxidative aging process, seen in
      vivo, in the acrylic bone cement mantles of total hip and knee joint
      replacements. For this purpose, quasi-static and dynamic nanoindentation
      measurements were used to obtain material properties--elastic modulus, E;
      hardness, H; and the variation of the storage and loss moduli with the frequency
      of the applied indenting force--of PalacosR acrylic bone cement specimens after
      various periods of immersion (7, 14, 21, and 28 days) in the aging solution, and
      of specimens prepared from cement mantles retrieved from cemented total hip joint
      replacements after various times in vivo (0.92-21 years). Also, best-fit
      relationships were obtained between E and time in the H(2)O(2) solution (t), H
      and t, E and in vivo time (T), and H and T. This body of results points to the
      possibility that the aging solution is effective, although the evidence is not
      conclusive.

PMID- 17041927
TI  - Neurotrophin-eluting hydrogel coatings for neural stimulating electrodes.
AB  - Improved sensory and motor prostheses for the central nervous system will require
      large numbers of electrodes with low electrical thresholds for neural excitation.
      With the eventual goal of reducing stimulation thresholds, we have investigated
      the use of biodegradable, neurotrophin-eluting hydrogels (i.e., poly(ethylene
      glycol)-poly(lactic acid), PEGPLA) as a means of attracting neurites to the
      surface of stimulating electrodes. PEGPLA hydrogels with release rates ranging
      from 1.5 to 3 weeks were synthesized. These hydrogels were applied to
      multielectrode arrays with sputtered iridium oxide charge-injection sites. The
      coatings had little impact on the iridium oxide electrochemical properties,
      including charge storage capacity, impedance, and voltage transients during
      current pulsing. Additionally, we quantitatively examined the ability of
      neurotrophin-eluting, PEGPLA hydrogels to promote neurite extension in vitro
      using a PC12 cell culture model. Hydrogels released neurotrophin (nerve growth
      factor, NGF) for at least 1 week, with neurite extension near that of an NGF
      positive control and much higher than extension seen from sham, bovine serum
      albumin-releasing boluses, and a negative control. These results show that
      neurotrophin-eluting hydrogels can be applied to multielectrode arrays, and
      suggest a method to improve neuron-electrode proximity, which could result in
      lowered electrical stimulation thresholds. Reduced thresholds support the
      creation of smaller electrode structures and high density electrode prostheses,
      greatly enhancing prosthesis control and function.

PMID- 17041928
TI  - Protective effects of antioxidants on micronuclei induced by camphorquinone/N,N
      dimethyl-p-toluidine employing in vitro mammalian test system.
AB  - Camphorquinone (CQ) is widely used as an initiator in modern visible-light (VL)
      cured resin systems. CQ is also characterized as a potential allergenic compound.
      To date, there is growing concern that CQ may produce genetic damage by inducing
      mutation. In this study, CQ in the presence of reducing agent N,N-dimethyl-p
      toluidine (DMT) with or without VL irradiation was analyzed for the induction of
      chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. Our
      data demonstrated that an increase in the numbers of MN was observed with CQ/DMT
      with or without VL irradiation (p < 0.05). Significant prolongation of cell
      cycles was observed by the treatment with CQ/DMT with or without VL irradiation
      (p < 0.05). In addition, VL irradiated CQ/DMT was found to exhibit significantly
      genotoxic and cytotoxic effects as compared with CQ/DMT alone (p < 0.05).
      Furthermore, to determine whether oxidative stress could modulate the MN induced
      by CQ/DMT with or without VL irradiation in CHO cells, cells were pre-treated
      with various antioxidants 10 mM N-acetyl-L-cysteine (NAC), 2 mM ascorbic acid,
      and 2 mM alpha-tocopherol. The pre-treatment with antioxidants could antagonize
      not only the increased MN cells but also the prolonged cell cycle induced by
      CQ/DMT with or without VL irradiation in CHO cells (p < 0.05). Our findings
      provide the evidences for the induction of MN by CQ/DMT employing mammalian test
      system, indicating clastogenic activity of CQ/DMT with or without VL irradiation
      in vitro. In addition, VL irradiated CQ/DMT exhibits higher genotoxic and
      cytotoxic effects than CQ/DMT alone. Moreover, NAC, ascorbic acid, and alpha
      tocopherol act as the antagonists against the genotoxicity and cytotoxicity of
      CQ/DMT with or without VL irradiation.

PMID- 17041929
TI  - Psychosocial outcomes of anxious first graders: a seven-year follow-up.
AB  - This study examined the concurrent and long-term psychosocial outcomes associated
      with anxiety symptoms among a community sample of predominately low-income
      African Americans (N=149; 72 females). We classified first graders as high or low
      anxious using child, parent, and teacher reports. Academic, social, and
      psychological outcomes were assessed in the first and eighth grades. Logistic
      regressions with concurrent data revealed that highly anxious children were
      significantly more likely to score lower on measures of academic achievement and
      peer acceptance, but higher on measures of depression and aggression compared to
      their low-anxious peers. Longitudinal analyses revealed that high-anxious first
      graders, compared to their low-anxious peers, scored significantly lower on
      measures of academic achievement, aggression, and peer acceptance; and higher on
      measures of anxiety and depression in the eighth grade. Importantly, outcomes
      varied depending on informant. Findings suggest that, similar to European
      American youth, early-onset anxious symptoms in African American children are
      associated with both concurrent and long-term academic, social, and psychological
      difficulties.

PMID- 17041930
TI  - Family-based association study of the MTHFR polymorphism C677T in the bladder
      exstrophy-epispadias-complex.

PMID- 17041931
TI  - Further phenotypic and genetic variation in ADULT syndrome.
AB  - ADULT (Acro-dermato-ungual-lacrimal-tooth) syndrome is characterized by
      ectrodactyly, syndactyly, fingernail and toenail dysplasia, hypoplasia of the
      breast and nipple, excessive freckling, lacrimal duct atresia, frontal alopecia,
      primary hypodontia, and/or early loss of permanent teeth. It is a rare autosomal
      dominant disorder which has been linked to mutation in the p63 gene. The p63 gene
      has been described in five overlapping limb malformation syndromes including the
      EEC syndrome (ectodermal ectrodactyly clefting). We report on the first case of
      ADULT syndrome of a mother and daughter with a new mutation R227Q in exon 6 of
      the p63 gene. This has not been previously associated with ADULT syndrome but
      only seen in EEC. In addition to the previously reported features of ADULT
      syndrome this report also describes some additional findings including
      hyperextensibility at the distal interphalageal joints, bilateral thumb
      duplication, bifid toenails, symptoms of urinary retention, vesicoureteric
      reflux, prominent ears, conductive hearing loss, and an overgrowth of a patch of
      hair in the midline of the neck. This report expands the knowledge of genotype
      phenotype data on the p63 gene and suggests there may be a considerable overlap
      between the EEC syndrome and the ADULT syndrome.

PMID- 17041932
TI  - Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8.
AB  - Trismus-pseudocamptodactyly syndrome (TPS) is a rare autosomal dominant distal
      arthrogryposis (DA) characterized by an inability to open the mouth fully
      (trismus) and an unusual camptodactyly of the fingers that is apparent only upon
      dorsiflexion of the wrist (i.e., pseudocamptodactyly). TPS is also known as Dutch
      Kentucky syndrome because a Dutch founder mutation is presumed to be the origin
      of TPS cases in the Southeast US, including Kentucky. To date only a single
      mutation, p.R674Q, in MYH8 has been reported to cause TPS. Several individuals
      with this mutation also had a so-called "variant" of Carney complex, suggesting
      that the pathogenesis of TPS and Carney complex might be shared. We screened MYH8
      in four TPS pedigrees, including the original Dutch family in which TPS was
      reported. All four TPS families shared the p.R674Q substitution. However,
      haplotype analysis revealed that this mutation has arisen independently in North
      American and European TPS pedigrees. None of the individuals with TPS studied had
      features of Carney complex, and p.R674Q was not found in 49 independent cases of
      Carney complex that were screened. Our findings show that distal arthrogryposis
      syndromes share a similar pathogenesis and are, in general, caused by disruption
      of the contractile complex of muscle.

PMID- 17041933
TI  - Childhood emotional, physical, and sexual abuse, and diagnoses of depressive and
      anxiety disorders in adult psychiatric outpatients.
AB  - Although a number of theorists have hypothesized a link between negative
      experiences during childhood (e.g., abuse) and the presence of psychopathology in
      adults, little is known about the relative specificity of childhood emotional,
      physical, or sexual abuse to different forms of psychopathology. In this study,
      we hypothesized that adult psychiatric outpatients' reports of childhood
      emotional abuse would exhibit a specific relationship with diagnoses of
      depression. Analyses partially supported our hypothesis. Specifically, diagnoses
      of major depression were significantly more strongly related to reports of
      childhood emotional abuse than to physical or sexual abuse. However, the same
      effect was observed for social phobia. In addition, patients with major
      depression reported equivalent levels of childhood emotional abuse as patients
      with social phobia, but lower levels of emotional abuse than those with
      posttraumatic stress disorder.

PMID- 17041934
TI  - Microdeletion and microduplication 22q11.2 screening in 295 patients with
      clinical features of DiGeorge/Velocardiofacial syndrome.
AB  - The 22q11.2 region is susceptible to chromosomal rearrangements, leading to
      various types of congenital malformation and mental retardation. The most common
      anomaly is 22q11.2 microdeletion, associated with DiGeorge/Velocardiofacial
      syndrome (DG/VCFS). Recently the microduplication 22q11.2 syndrome has been
      identified. Some clinical features in patients with this new chromosomal disorder
      present a substantial overlap with DG/VCFS. The aim of this hospital-based study
      was to evaluate the incidence of deletions and duplications on 22q11.2 in
      patients with DG/VCFS features. We investigated a group of 295 patients with
      widely variable manifestations associated with DG/VCFS. Along with the clinical
      diagnoses different anomalies were noted such as conotruncal cardiac anomaly,
      velopharyngeal insufficiency, characteristic facial dysmorphic features, language
      impairment, developmental delay/learning difficulties, and immunologic anomalies
      or thymic hypoplasia. Laboratory studies included conventional cytogenetic and
      FISH testing. Metaphase and interphase cells were analyzed for the presence of
      22q11.2 microdeletion or microduplication. There were 12 patients who carried
      22q11.2 microdeletion and no microduplication in the region was identified. Other
      chromosomal anomalies were reported in five patients with an overlapped DG/VCFS
      phenotype. All patients with 22q11.2 microdeletion showed a characteristic
      phenotype of DG/VCFS. We did not identify 22q11.2 microduplication, suggesting
      that this is a rare event in patients with DG/VCFS features.

PMID- 17041936
TI  - DLL3 as a candidate gene for vertebral malformations.
AB  - Investigations have not identified a major locus for congenital vertebral
      malformations. Based on observations in mice, we hypothesized that mutations in
      DLL3, a member of the notch-signaling pathway, might contribute to human
      vertebral malformations. We sequenced the DLL3 gene in 50 patients with
      congenital vertebral malformations. A Caucasian male patient with VACTERL
      manifestations including a T5-T6 block vertebrae was heterozygous for a "G" to
      "A" missense mutation changing glycine to arginine at codon 269. This residue is
      conserved in mammals, including chimpanzee, mouse, dog, and rat. Additional
      testing in the patient did not show evidence of chromosome abnormalities. The
      patient's asymptomatic mother was also heterozygous for the missense mutation.
      Since this mutation was not observed in a control population and leads to an
      amino acid change, it may be clinically significant. The mutation was not found
      in a control population of 87 anonymous individuals. Several established
      mechanisms could explain the mutation in both the patient and his asymptomatic
      mother (susceptibility allele requiring additional environmental factors, somatic
      mosaicism, multigenic inheritance). Documenting the absence of the mutation in a
      larger control population or the presence of the mutation in additional affected
      patients, or documenting a functional difference in DLL3 would provide further
      evidence supporting its causal role.

PMID- 17041937
TI  - Tracking rare incidence syndromes (TRIS) project.

PMID- 17041935
TI  - Obsessive-compulsive disorder versus body dysmorphic disorder: a comparison study
      of two possibly related disorders.
AB  - The relationship between obsessive-compulsive disorder (OCD) and body dysmorphic
      disorder (BDD) is unclear. BDD has been proposed to be an OCD-spectrum disorder
      or even a type of OCD. However, few studies have directly compared these
      disorders' clinical features. We compared characteristics of subjects with OCD
      (n=210), BDD (n=45), and comorbid BDD/OCD (n=40). OCD and BDD did not
      significantly differ in terms of demographic features, age of OCD or BDD onset,
      illness duration, and many other variables. However, subjects with BDD had
      significantly poorer insight than those with OCD and were more likely to be
      delusional. Subjects with BDD were also significantly more likely than those with
      OCD to have lifetime suicidal ideation, as well as lifetime major depressive
      disorder and a lifetime substance use disorder. The comorbid BDD/OCD group
      evidenced greater morbidity than subjects with OCD or BDD in a number of domains,
      but differences between the comorbid BDD/OCD group and the BDD group were no
      longer significant after controlling for BDD severity. However, differences
      between the comorbid BDD/OCD group and the OCD group remained significant after
      controlling for OCD severity. In summary, OCD and BDD did not significantly
      differ on many variables but did have some clinically important differences.
      These findings have implications for clinicians and for the classification of
      these disorders.

PMID- 17041938
TI  - Frontonasal malformation, first branchial arch anomalies, congenital heart
      defect, and severe central nervous system involvement: a possible "new" autosomal
      recessive syndrome?
AB  - Here we report on a girl presenting with midline cleft lip/palate, prominent
      forehead, macrocephaly, first branchial arch anomalies, and tetralogy of Fallot.
      Imaging studies showed polymicrogyria, enlarged ventricles with a large cystic
      lesion extending postero-superiorly over the cerebellum, abnormally modeled
      cerebellum, and congenital aqueductal stenosis. To our knowledge, this
      combination of clinical signs involving the frontonasal process, midline lip
      clefting, congenital heart malformation, and severe CNS developmental
      abnormalities has not previously been reported. Clinical, imaging data, as well
      as differential diagnosis are discussed.

PMID- 17041939
TI  - Antenatal screening tests: knowledge and practice patterns of obstetricians in
      Utah.
AB  - We sought to assess knowledge and practices of obstetricians regarding antenatal
      testing and test the efficacy of continuing education via a direct mailing. In
      June 2004, an educational brochure entitled "New Options for Maternal Serum
      Screening for Birth Defects" as well as an anonymous survey pertaining to
      antenatal testing was sent to 241 American College of Obstetricians and
      Gynecologists (ACOG) Fellows and Junior Fellows residing in Utah. Data from the
      85 (35%) respondents were analyzed. The majority of respondents practice
      obstetrics (81/85, or 95%). Of these, 67% of respondents perform sonograms
      routinely in their offices. Respondents were distributed evenly across all years
      of practice. Respondents offer HIV screening routinely (85%), but only 40% follow
      ACOG cystic fibrosis (CF) screening recommendations. Midtrimester serum screening
      is offered routinely by 89% of the respondents, but only 54% adequately
      understood the capabilities and limitations of the test. Questions related to the
      patient education brochure included in the mailing were answered correctly more
      often than the other questions. The brochure emphasized the usefulness of
      combined integrated screening for detecting Down syndrome, and 94% of respondents
      subsequently understood this concept. We show that in Utah, ACOG recommendations
      for HIV and maternal serum testing are being followed uniformly, but CF screening
      is still not being routinely offered. The accurate responses to questions related
      to an enclosed education brochure suggest that direct mailings may be useful for
      provider education, especially in regions where many providers practice remote
      from academic centers.

PMID- 17041940
TI  - No association between periconceptional multivitamin supplementation and risk of
      multiple congenital abnormalities: a population-based case-control study.
AB  - Two previous Hungarian intervention trials showed that periconceptional folic
      acid-containing multivitamin supplementation did not change the total (birth +
      fetal) prevalence of cases with multiple congenital abnormalities (MCAs).
      However, two US observational studies found an elevated risk for MCAs in the
      offspring of women who reported periconceptional use of multivitamins containing
      folic acid. These conflicting results stimulated us to evaluate the data set of
      the Hungarian Case-Control Surveillance of Congenital Abnormalities and to check
      the possible association between the use of periconceptional multivitamin
      supplementations and the total prevalence of cases with MCAs. Of 1,349 cases with
      MCA, 69 (5.1%) had mothers who used multivitamins during the second and third
      month of pregnancy. Of 2,405 matched controls without any defect, 126 (5.2%) had
      mothers who used multivitamin supplementation in early pregnancy. Of 21,494
      malformed controls with isolated congenital abnormalities, 1,052 (4.9%) mothers
      received supplementation with multivitamins during the critical period of CAs
      including MCAs. There was no difference in the use of multivitamins among the
      study groups either in the total data set or at the evaluation of only
      prospective medically recorded data. Medically recorded folic acid use without
      any multivitamins in the second and third gestational month showed some
      protective effect for MCAs. In conclusion, our observational case-control study
      did not detect a folic acid containing multivitamins during the early pregnancy
      as a risk factor for MCAs.

PMID- 17041941
TI  - Genotype-phenotype correlations in cerebral cavernous malformations patients.
AB  - OBJECTIVE: To compare clinical features of CCM1, CCM2, and CCM3 mutation
      carriers. METHODS: A detailed clinical and molecular analysis of 163 consecutive
      cerebral cavernous malformation (CCM) families was performed. RESULTS: A
      deleterious mutation was detected in 128 probands. Three hundred thirty-three
      mutation carriers were identified (238 CCM1, 67 CCM2, and 28 CCM3). Ninety-four
      percent of the probands with an affected relative had a mutation compared with
      57% of the probands with multiple lesions but no affected relative (p < 0.001).
      The number of affected individuals per family was lower in CCM3 families (p <
      0.05). The proportion of patients with onset of symptoms before 15 years of age
      was higher in the CCM3 group (p < 0.0025). Cerebral hemorrhage was the most
      common initial presentation in CCM3 patients. The average number of T2-weighted
      imaging lesions was similar in the three groups, in contrast with a significantly
      lower number of gradient-echo sequence lesions in CCM2 patients (p < 0.05). The
      number of gradient-echo sequence lesions increased more rapidly with age in CCM1
      than in CCM2 patients (p < 0.05). INTERPRETATION: Despite similarities among the
      three groups, there is a significantly lower number of affected individuals in
      CCM3 pedigrees, CCM3 mutations may confer a higher risk for cerebral hemorrhage,
      particularly during childhood, and the increment of gradient-echo sequence
      lesions with age differs between CCM1 and CCM2 patients.

PMID- 17041942
TI  - RAI1 point mutations, CAG repeat variation, and SNP analysis in non-deletion
      Smith-Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental
      retardation disorder characterized by distinct craniofacial features and
      neurobehavioral abnormalities usually associated with an interstitial deletion in
      17p11.2. Heterozygous point mutations in the retinoic acid induced 1 gene (RAI1)
      have been reported in nine SMS patients without a deletion detectable by
      fluorescent in situ hybridization (FISH), implicating RAI1 haploinsufficiency as
      the cause of the major clinical features in SMS. All of the reported point
      mutations are unique and de novo. RAI1 contains a polymorphic CAG repeat and
      encodes a plant homeo domain (PHD) zinc finger-containing transcriptional
      regulator. We report a novel RAI1 frameshift mutation, c.3103delC, in a non
      deletion patient with many SMS features. The deletion of a single cytosine occurs
      in a heptameric C-tract (CCCCCCC), the longest mononucleotide repeat in the RAI1
      coding region. Interestingly, we had previously reported a frameshift mutation,
      c.3103insC, in the same mononucleotide repeat. Furthermore, all five single base
      frameshift mutations preferentially occurred in polyC but not polyG tracts. We
      also investigated the distribution of the polymorphic CAG repeats in both the
      normal population and the SMS patients as one potential molecular mechanism for
      variability of clinical expression. In this limited data set, there was no
      significant association between the length of CAG repeats and the SMS phenotype.
      However, we identified a 5-year-old girl with an apparent SMS phenotype who was a
      compound heterozygote for an RAI1 missense mutation inherited from her father and
      a polyglutamine repeat of 18 copies, representing the largest known CAG repeat in
      this gene, inherited from her mother.

PMID- 17041944
TI  - Age-dependent decreases in mitogen-stimulation level and RNA content in
      peripheral blood mononuclear cells of Down syndrome patients.
AB  - OBJECTIVE: The aim of the present study was to determine whether or not the
      phytohemagglutinin (PHA)-activated proliferation and average RNA content in
      peripheral blood mononuclear cells (PBMC) of Down syndrome (DS) patients change
      with age. METHOD: Stimulated portion of PBMC and total RNA levels in these cells
      after 72 h of PHA stimulation from 38 DS patients were compared with 28 age
      matched healthy controls using flow cytometric measurement. RESULTS: Decreased
      ratio of PBMC from DS patients undergoes mitogenic stimulation with age (r = 
      0.84, P = 0.000). This decrease is not observed in the cells of control
      individuals (r = 0.03, P = 0.869). Stimulated PBMC in infants with DS have higher
      level of RNA contents compared to controls (Z = 2.227, P = 0.026). While RNA
      content in mitogen-stimulated PBMC of DS decreased progressively and
      significantly with age (r = -0.70, P = 0.000), no significant age-related change
      in RNA content was found among the cells of healthy individuals in the range of 0
      27 year old (r = 0.275, P = 0.157, P > 0.05). CONCLUSION: Age-dependent decreases
      in mitogen-activated proliferation ratio and average RNA content of PBMC from DS
      patients appear as regular events. These results may contribute to the
      explanation of the immune deficiency seen in DS patients since the PHA-stimulated
      cells are principally T-lymphocytes. This is the first report on the decrease in
      PHA-stimulated proliferation ratio (stimulability) and RNA level in PBMC of DS
      patients in relation to age.

PMID- 17041943
TI  - DNA sequence analysis of GJB2, encoding connexin 26: observations from a
      population of hearing impaired cases and variable carrier rates, complex
      genotypes, and ethnic stratification of alleles among controls.
AB  - Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of
      GJB2 in a cohort of hearing impaired patients and a multi-ethnic control group is
      reported. Among 610 hearing impaired cases, 43 DNA sequence variations were
      identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms,
      3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and
      7 novel variants (G12C, N14D, V63A, T86M, L132V, D159,
      592_600delinsCAGTGTTCATGACATTC). Sixteen non-coding sequence variations were also
      identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13
      novel variants. A diagnosis of GJB2-associated hearing loss was confirmed for 63
      cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases
      carrying novel or unclassified variants (1.8 %) and 18 cases carrying the
      controversial V37I variant were identified (3%). In addition, 294 control
      subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence
      variations in the coding region of GJB2 were identified among controls including
      2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1
      controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence
      variations were identified among controls in the non-coding regions in and around
      GJB2 exon 2. Of particular interest among controls were the variability in
      carrier rates and ethnic stratification of alleles, and the complex genotypes
      among Asians, 47% of whom carried two to four sequence variations in the coding
      region of GJB2. These data provide new information about carrier rates for GJB2
      based hearing loss in various ethnic groups and contribute to evaluation of the
      pathogenicity of the controversial V37I variant.

PMID- 17041945
TI  - HIV-1-infected children on HAART: immunologic features of three different levels
      of viral suppression.
AB  - BACKGROUND: HIV-1-infected children show changes of blood lymphocyte
      subpopulations. We have, therefore, investigated how highly active anti
      retroviral therapy (ART) alter these subsets. Blood samples were taken from 41
      HIV-1-infected children on ART who were divided into groups showing good, partial
      and poor responses to ART on the basis of viral load (VL) measurement in blood.
      The observations were compared to those seen in 20 uninfected children. METHODS:
      The samples were studied using 4-color flow cytometry for "naive", central memory
      and effector memory cells as well as for CD38 expression as the sign of
      activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected
      children were also evaluated for the presence and the titers of antibodies
      induced by vaccination against childhood infections in our patients while on
      HAART. RESULTS: Lymphocyte counts were lower in the "poor" viral load responding
      (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total
      and naive CD4+ T cell counts. HIV-1-infected children from all three groups had
      high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were
      particularly low in the poor VLR group while in the poor VLR group the
      percentages of effector memory CD4+ and CD8+ T cells were higher when compared
      with the control group. Higher cellular activation of CD8+ T cells was observed
      in HIV-1-infected children, particularly when analyzed for the intensity of CD38
      expression in the poor VLR group. CD5 expression on B cells was higher among all
      HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and
      hepatitis B were present in a large proportion of children but the titers were
      similarly low for all three groups of HIV-infected children. CONCLUSIONS:
      Children with different levels of viral response to HAART present immune
      phenotype characteristics that tend to place the children with partial and good
      virological responses into the same group. These children are still moderately
      deficient in their immune responses but show better recovery than seen with
      children in the poor VLR group. These observations indicate that the proportions
      of central memory cells among the CD4+ T cells and the intensity of the
      expression of CD38 activation antigen on CD8+ T cells provide more informative
      parameters for monitoring children on HAART than the absolute numbers of CD4+ and
      CD8+ T cells alone.

PMID- 17041946
TI  - National standardization of ZAP-70 determination by flow cytometry: the French
      experience.
AB  - BACKGROUND: ZAP-70, after being considered as a potential surrogate for VH
      mutational status, has seen its own prognostic value emerge. We aimed at
      standardizing a simple, fast, and reproducible flow cytometry method. METHODS:
      AntiZAP-70 antibody 2F3.2 was used with indirect labeling and secondary anti
      IgG2a antibody. The reference values for the expression of the results were
      determined on 45 normal blood samples. ZAP-70 protein expression was investigated
      in 192 CLL samples. The indirect technique was compared with FITC-conjugated
      2F3.2 clone, and with clone 1E7.2-FITC, -PE or -AlexaFluor 488. RESULTS: Using
      FITC or PE-conjugated antibodies, 2F3.2 and 1E7.2 clones allowed a much less
      adequate discrimination between positive and negative cells and discordant cases
      were most likely true negative cases. Using the AlexaFluor 488 conjugated 1E7.2
      clone, the discordant cases were mostly negative with the conjugated antibody and
      positive with the 2F3.2 clone but Western blotting or RNA microarray confirmed
      discordant cases were false negative with the conjugated antibody. Subsequently,
      recommendations were used by 13 centers participating in an interlaboratory
      quality control protocol. The use of MFI ratio appeared to be more reliable.
      CONCLUSIONS: Results suggested that slight differences in the procedure had
      little impact on the interpretation in characteristic cases; however, careful
      interpretation was required for values close to threshold.

PMID- 17041947
TI  - Fluoxetine treatment increases trabecular bone formation in mice.
AB  - Mounting evidence exists for the operation of a functional serotonin (5-HT)
      system in osteoclasts and osteoblasts, which involves both receptor activation
      and 5-HT reuptake. In previous work we showed that the serotonin transporter (5
      HTT) is expressed in osteoclasts and that its activity is required by for
      osteoclast differentiation in vitro. The purpose of the current study was to
      determine the effect of treatment with fluoxetine, a specific serotonin reuptake
      inhibitor, on bone metabolism in vivo. Systemic administration of fluoxetine to
      Swiss-Webster mice for 6 weeks resulted in increased trabecular BV and BV/TV in
      femurs and vertebrae as determined by micro-computed tomography (microCT). This
      correlated with an increase in trabecular number, connectivity, and decreased
      trabecular spacing. Fluoxetine treatment also resulted in increased volume in
      vertebral trabecular bone. However, fluoxetine-treated mice were not protected
      against bone loss after ovariectomy, suggesting that its anabolic effect requires
      the presence of estrogen. The effect of blocking the 5-HTT on bone loss following
      an LPS-mediated inflammatory challenge was also investigated. Subcutaneous
      injections of LPS over the calvariae of Swiss-Webster mice for 5 days resulted in
      increased numbers of osteoclasts and net bone loss, whereas new bone formation
      and a net gain in bone mass was seen when LPS was given together with fluoxetine.
      We conclude that fluoxetine treatment in vivo leads to increased bone mass under
      normal physiologic or inflammatory conditions, but does not prevent bone loss
      associated with estrogen deficiency. These data suggest that commonly used anti
      depressive agents may affect bone mass.

PMID- 17041948
TI  - Improvement of diagnostic accuracy and screening conditions with liquid-based
      cytology.
AB  - The aim of this population-based study was to compare the histological follow-up
      diagnoses of cervicocytological neoplasia (dysplasia, carcinoma in situ and
      carcinoma) in conventional Papanicolaou (CP) smear and ThinPrep PapTest samples
      (TP). All cytological samples from the County of Funen, Denmark, in the periods
      2000 (n = 34,832) and 2002 (n = 29,995) were included in the study. In 2000 and
      2002, the specimens were CP and TP, respectively. The detection rate of > or =
      mild dysplasia was 0.8% in CP and 1.4% in TP, showing a 75% increase in TP when
      compared with CP (p < 0.001). Histological follow-up of > or = moderate dysplasia
      revealed a neoplastic lesion in 77.1% and 87.9% in CP and TP, respectively (P <
      0.001). The present study indicates that the diagnostic accuracy of cervical
      cytology is improved with liquid-based cytology. In addition, we focus on the
      optimized cellular material that shows the diagnostic details very clearly to the
      microscopist and leads to radically improved screening conditions.

PMID- 17041949
TI  - Salivary gland crystalloids.

PMID- 17041950
TI  - Fine needle aspiration cytology of lipomatous lesions of the thyroid.

PMID- 17041951
TI  - Fine-needle aspiration cytology of an intrathyroid parathyroid adenoma.

PMID- 17041952
TI  - Pneumatosis cystoides intestinalis--is it possible to diagnose it by fine-needle
      aspiration cytology?

PMID- 17041953
TI  - Pancreatic mucinous lesions: a retrospective analysis with cytohistological
      correlation.
AB  - The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic
      adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic
      neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical
      management and prognosis. This retrospective study is done to assess the
      cytological features and pitfalls associated with these entities in cytological
      samples.A search for pancreatic cytology specimens with histological confirmation
      of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous
      adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37)
      had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity,
      background extracellular mucin, epithelial architecture, mucinous nature of the
      epithelium, cell shape, and nuclear features were evaluated on the cytology
      material. Of the 22 cytological features evaluated, the presence of three
      dimensional clusters, micropapillary structures, and nuclear atypia, which
      includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane
      contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be
      consistently associated with mucinous adenocarcinoma. There were no statistically
      significant cytological features, which helped in differentiating IPMN, MCN, and
      mucinous metaplasia. There was a relatively high false-positive rate in the IPMN
      group (5/14, 36%). Review of the histological specimen showed severe dysplastic
      epithelial change in these cases. One false-positive case of mucinous metaplasia
      (1/3, 33%) showed marked intraepithelial acute inflammation. The cytological
      diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous
      noncystic adenocarcinoma. The findings were largely nonspecific in the
      differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled
      gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs
      not infrequently in the setting of IPMN with severe dysplastic epithelial change
      and in lesions with associated acute inflammation, and can be a pitfall in the
      diagnosis of these lesions.

PMID- 17041954
TI  - Utility of reflex Gomori methenamine silver staining for Pneumocystis jirovecii
      on bronchoalveolar lavage cytologic specimens: a review.
AB  - Pneumocystis jiroveci (Pj; formerly Pneumocystis carinii) is an opportunistic
      pathogen causing life-threatening pneumonia (Pneumocystis pneumonia) in
      immunosuppressed individuals. Its diagnosis is dependent on identification in
      bronchoalveolar lavage (BAL) specimens. Gomori's methenamine silver nitrate (GMS)
      stain has been advocated to highlight the organisms in BAL specimens. This study
      was performed to determine the utility of reflex GMS staining on all BAL
      specimens for identifying Pj.All BAL specimens from years 2000 to 2004 were
      processed as cytospins and stained with Papanicolaou (Pap) and GMS stains. A
      total of 2,984 BAL specimens were identified. A total of 116 (3.9% of total BAL)
      BAL specimens were diagnostic of Pj. The diagnostic specimens were grouped as
      follows: 103 (88.8% of total positive cases) Pj identified with both Pap and GMS
      staining; 11 (9.5% of total positive cases) Pj identified only with Pap staining;
      and 2 (1.7% of total positive cases) Pj identified only with GMS staining. In
      conclusion, the prevalence of Pj in BAL specimens is 3.9%, which can be
      attributed to improved management of immunocompromised patients. Performing
      reflex GMS staining on all BAL specimens does not improve the diagnostic
      identification of Pj since the majority (98.3%) of diagnoses can be rendered on
      Pap stained slides. A cost analysis for GMS staining on 2,879 GMS-negative BAL
      specimens was estimated at $143,950. Thus, from diagnostic and cost benefit
      perspectives, GMS staining can be recommended only on cases where Pap stain is
      negative, and the clinical presentation is consistent with Pneumocystis
      pneumonia.

PMID- 17041955
TI  - ASC-US and high-risk HPV testing: performance in daily clinical practice.
AB  - Data are beginning to accrue on high-risk HPV DNA testing in patients with ASC-US
      on cervical cytology. We report on our experience at the University of Wisconsin
      Hospital and Clinics. From February 2002 through December 31, 2005 (3 yr, 11 mo),
      the cytopathology laboratory processed 49,599 Pap Tests, of which 1,792 (3.6%)
      were diagnosed as ASC-US. Six hundred and seventy two (37.5%) of these cases were
      processed for high-risk HPV genotypes using the Digene Hybrid Capture II method.
      Of these cases, 266 (39.6%) were positive for high-risk HPV genotypes, 11 (1.6%)
      were equivocal, and 395 (58.8%) were negative. Biopsy follow-up was available for
      127 (47.7%) of the 266 cases, of which 66 (52%) were negative, 46 (36.2%) showed
      CIN I, 9 (7.1%) were CIN II, and 6 (4.7%) were CIN III. Of the remaining 139
      (52.3%) cases, 86 (62%) had follow-up Pap Tests, of which 57 (66.3%) were
      negative, 15 (17.4%) were ASC-US, 12 (15%) were low-grade squamous
      intraepithelial lesions, and 2 (2.3%) were high-grade squamous intraepithelial
      lesions; 53 (38.1%) were lost to follow-up. In combination, 90 (42.25%) of the
      213 cases with follow-up showed atypia or above after a diagnosis of ASC-US; of
      which 58 (64%) were low-grade lesions and 17 (19%) were high-grade lesions. Our
      laboratory's reported high-risk HPV positivity is comparable to recent reports in
      the literature on its use in daily clinical practice. In addition, cervical
      abnormalities were found in a significant proportion of the cases.

PMID- 17041956
TI  - Cost efficiency analysis for fine-needle aspiration in the workup of parotid and
      submandibular gland nodules.
AB  - The utility and cost effectiveness of salivary gland fine-needle aspiration (FNA)
      is controversial. Some authorities argue FNA has no added value over clinical
      radiographic study because most salivary gland nodules occur in the parotid and
      the tumor's relationship to the facial nerve determines the operative procedure
      rather than the histology. Other experts contend FNA is of value by reducing the
      overall number of operative procedures performed. We studied 306 salivary gland
      nodules (214 parotid and 92 submandibular gland) undergoing FNA. One hundred and
      seventy one were subsequently surgically resected and the remaining 135 followed
      clinically. A 16% error rate was associated with the nonoperative group,
      necessitating later surgical resection. The cost of the FNAs and surgical
      resections (when performed) was calculated based on Medicare reimbursement rates.
      Costs were based on all cases undergoing initial FNA. The expense of initial
      resection was based on the observed percentage of patients undergoing resection
      in our series. The costs of resections related to erroneous FNA diagnoses were
      based on the error rate associated with FNA diagnoses clinically followed (i.e.,
      chronic sialadenitis). Costs of FNAs, initial resections, and subsequent
      resections related to FNA errors were summed and compared with the cost which
      would have occurred if all nodules had been primarily resected.FNA reduced the
      number of operative procedures by approximately 65% for submandibular nodules and
      35% for parotid nodules. Diagnoses which resulted in nonsurgical management
      included chronic radiation-induced sialadenitis, intraparotid lymph node,
      recurrent lymphoma, and accessory nodules or lobes of the parotid gland. Pure
      surgical management was associated with a cost of $275,750.00 per 100 patients.
      FNA management was associated with an expenditure of $206,632.00 per 100
      patients, representing a savings of $69,118.00 (33% savings over surgical
      management alone). Based on these data, FNA appears to be cost effective in
      addition to supplying preoperative diagnoses helpful in counseling, operative
      planning, and allaying patient anxiety.

PMID- 17041957
TI  - Upregulation of telomerase (hTERT) is related to the grade of cervical
      intraepithelial neoplasia, but is not an independent predictor of high-risk human
      papillomavirus, virus persistence, or disease outcome in cervical cancer.
AB  - Telomerase activation and telomere maintenance are essential for cell
      immortalization and represent a rate-limiting step in cancer progression. The E6
      oncoprotein of high-risk human papillomavirus (HPV) is known to activate
      telomerase, but its expression in CIN lesions and its prognostic value in
      cervical cancer (CC) are still incompletely understood. As part of our HPV
      PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using
      immunohistochemical (IHC) staining for hTERT (telomerase reverse transcriptase),
      and tested for HPV using PCR with three primer sets (MY09/11, GP5(+)/GP6(+),
      SPF). Follow-up data were available from all SCC patients, and 67 CIN lesions had
      been monitored with serial PCR for HPV after cone treatment. Expression of hTERT
      was increased in parallel with the grade of CIN, with major up-regulation upon
      transition to CIN3 (OR 18.81; 95% CI 8.48-41.69; P = 0.0001). Positive hTERT
      expression was 90% specific indicator of CIN, with 98.7% PPV, but suffers from
      low sensitivity (57.5%) and NPV (14.3%). hTERT expression was also significantly
      associated to HR-HPV with OR 3.38 (95% CI 1.90-6.02; P = 0.0001), but this
      association was confounded by the histological grade (Mantel-Haenszel common OR =
      1.83; 95% CI 0.92-3.79; P = 0.086). Expression of hTERT did not predict
      clearance/persistence of HR-HPV after treatment of CIN, and it was not a
      prognostic predictor in cervical cancer in univariate or multivariate survival
      analysis. It was concluded that up-regulation of hTERT was closely associated
      with HR-HPV, due to activation by the E6 oncoprotein. hTERT is a late marker of
      cervical carcinogenesis, significantly associated with progression to CIN3.
      Theoretically, a combination of hTERT assay (showing high SP and PPV) with
      another test showing high SE and high NPV (e.g. Hybrid Capture 2 for HPV), should
      provide an ideal screening tool capable of high-performance detection of CIN
      lesions.

PMID- 17041958
TI  - Fine-needle aspiration biopsy findings in epithelioid myoepithelioma of the
      parotid gland: a case report.
AB  - We describe the fine-needle aspiration biopsy findings in a case of epithelioid
      myoepithelioma of the parotid gland in a 24-yr-old male. The cytologic features
      of myoepithelioma of the parotid gland are only documented in a few case reports
      and we believe the cytologic description of the epithelioid variant has been
      described in only one other case. The differential diagnosis with other salivary
      gland neoplasms is discussed.

PMID- 17041959
TI  - Bioremediation potential of live and dead Spirulina: spectroscopic, kinetics and
      SEM studies.
AB  - Metal binding by algae has enormous potential for environmental bioremediation
      targeting towards detoxification of water bodies. The present work reports the
      use of live and dead Spirulina sp. for sorption of metals like Cr(3+), Ni(2+),
      Cu(2+), and Cr(6+) in form of Cr(2)O(7)(2-). Preliminary investigation shows that
      this biomass takes up substantial amount of metal ions indicated above. IR
      spectroscopic study, kinetics models, Langmuir and Freundlich adsorption
      isotherms, SEM analysis, and fluorescence microscopic study of Spirulina sp. and
      the Spirulina sp. treated with different metal ions have been employed to
      understand the sorption mechanism. It is hoped that live Spirulina sp. will be a
      strong candidate for management of industrial wastewater.

PMID- 17041960
TI  - Immunological characterization of a newly developed antibody for localization of
      a beta-keratin in turtle epidermis.
AB  - Turtle scutes are made of hard (beta)-keratins. In order to study size and
      localization of beta-keratins in turtle shell, we produced a rat polyclonal
      antiserum against a turtle scute beta-keratin of 13-16 kDa, which allowed the
      immunolocalization of the protein in the epidermis. In immunoblots the antiserum
      recognized turtle beta-keratins but showed variable cross-reactivity with lizard,
      snake, and avian beta-keratins. The turtle antiserum appears less cross-reactive
      than a chicken scale antiserum (Beta-1). In bidimensional immunoblots, three main
      protein spots at 15-16 kDa with pI at 7.3, 6.8, 6.4, and an unresolved large spot
      at 40-45 kDa with pI around 5 were more constantly obtained. The latter may
      result from the aggregation of the smaller beta-keratin protein. The corneous
      layer of the carapace and plastron of various species of chelonians appeared
      immunofluorescent. The ultrastructural immunolocalization showed sparse labeling
      over beta-keratin filaments of cells of the horny layer of both carapace and
      plastron. The study for the first time shows that the isolated protein band
      derived from a component of the beta-keratin filaments of the corneous layer of
      turtles. This antibody can be used for further studies on beta-keratin expression
      and sequencing in chelonian shell. No labeling was present over other cell
      organelles or layers of turtle epidermis and it was absent in non-epidermal
      cells. The specificity for turtle beta-keratin suggests that the antiserum
      recognizes some epitope/s specific for chelonians beta-keratins, and that it also
      variably recognizes other reptilian and avian beta-keratins.

PMID- 17041961
TI  - Germ cell depletion does not alter the morphogenesis of the fetal testis or ovary
      in the red-eared slider turtle (Trachemys scripta).
AB  - In the red-eared slider turtle, Trachemys scripta, both prospective male and
      female gonads contain primitive cord structures at the time when the gonad first
      forms. Primordial germ cells arrive in the gonad and accumulate on the coelomic
      surface. If testis development is initiated, these cords develop further at the
      same time that germ cells migrate from the coelomic surface and become
      sequestered in the interior of the cords. In contrast, in the developing ovary
      germ cells proliferate in a defined cortical domain, while the primitive cords
      regress and form flattened lacunae in the medulla. Because of their intimate
      association with these developmental processes, we investigated whether germ
      cells were required in turtles to establish the morphology of the fetal testis
      and ovary. We present evidence that normal morphological development of the fetal
      gonad occurs in both sexes in T. scripta after germ cell depletion, suggesting a
      conservation of developmental mechanisms across vertebrates.

PMID- 17041963
TI  - The objectives and work of the National Rheumatoid Arthritis Society.

PMID- 17041964
TI  - Overview of the psychosocial concerns of young adults with juvenile arthritis.
AB  - Young adults who develop juvenile idiopathic arthritis in childhood have a
      significant risk of long-term morbidity and continuing disease activity in
      adulthood. The impact of a physically restricting and painful chronic illness can
      make the transition from adolescence to adulthood more challenging. In this
      overview of the psychological and social impact of juvenile arthritis on young
      adults, particular attention is given to those areas that are of concern to this
      age group. The transition from adolescence to adulthood can be detrimentally
      affected not only by the attitudes of peers and parents, but also by the
      attitudes of the individual with arthritis. Chronic arthritis, including juvenile
      arthritis, is related to increased rates of anxiety and depression. In the face
      of functional restriction, pain, and poor body image, social and sexual
      relationships may be harder to develop and maintain. The family of the young
      adult may also be affected on many levels. Employment and financial security are
      common and well-founded concerns of young disabled adults.

PMID- 17041962
TI  - Expression profiling of BEN regulated genes in mouse embryonic fibroblasts.
AB  - BEN is a member of the TFII-I family of helix-loop-helix transcription factors.
      Both TFII-I and BEN are involved in gene regulation through interactions with
      tissue-specific transcription factors and chromatin remodeling complexes.
      Identification of the downstream target genes of TFII-I proteins is critical in
      delineating the regulatory effects of these proteins. In this study, we conducted
      a microarray analysis to determine gene expression alterations following the
      overexpression of BEN in primary mouse embryonic fibroblasts (MEFs). We found the
      BEN-dependent modulation in the expression of large groups of genes representing
      a wide variety of functional categories including genes important in the immune
      response, cell cycle, transcriptional regulation and cell signaling. A set of
      genes identified by the microarray analysis was validated by independent real
      time PCR analysis. Among upregulated genes were Shrm, Tgfb2, Ube2l6, G1p2, Ccl7
      while downregulated genes were Folr1, Tgfbr2, Csrp2, and Dlk1. These results
      support a versatile function of TFII-I proteins in vertebrate physiology and lead
      to an increased understanding of the BEN-dependent molecular events.

PMID- 17041965
TI  - Being a parent or grandparent with back pain, ankylosing spondylitis or
      rheumatoid arthritis: a descriptive postal survey.
AB  - Research that explores being a parent or grandparent with musculoskeletal
      problems has been fairly limited to date. The aim of this study was to describe
      the experience of parenting in the context of back pain (BP), ankylosing
      spondylitis (AS) and rheumatoid arthritis (RA), with a particular focus on the
      extent and nature of childcare experiences and to compare these experiences
      across the three groups. In addition, the possible reasons for these reported
      experiences, the availability of advice and support and the development of
      strategies for coping were explored using a cross-sectional descriptive survey. A
      total of 448 participants was recruited from relevant charitable organizations
      and the National Health Service (280 with BP, 106 with AS and 62 with RA). A
      combination of opportunistic and random sampling was used. Quantitative data were
      analysed with appropriate descriptive and inferential statistics using
      Statistical Package for the Social Sciences (SPSS version 10). Qualitative data
      were analysed using content analysis. Results indicate that a high proportion of
      all groups experienced a wide range of difficulties with parenting (81% BP, 77%
      AS, 97% RA). The most prevalent problems were similar for all three groups:
      lifting baby/child from the floor or cot, encouraging children/grandchildren to
      help with domestic chores and keeping up (in terms of energy) with
      children/grandchildren. However, the RA group reported having greater
      difficulties than the other two groups. Very little advice was offered to
      participants with parenting difficulties which may indicate a gap in service
      provision. However, a wide range of strategies for coping were described by
      respondents. The study highlighted a need for healthcare professionals to develop
      a greater awareness of parenting issues and to provide opportunities for these
      issues to be addressed.

PMID- 17041966
TI  - A review of the history of hand exercises in rheumatoid arthritis.
AB  - The management of the hand in the patient with rheumatoid arthritis (RA) is a
      challenge to all therapists and evidence for optimum management historically
      scarce. Given that it is estimated that hands and wrists are affected in 80-90%
      of RA patients (Maini and Feldmann, 1998), it is apparent that this is an
      important area for both the patient and practitioner. While acknowledging the
      importance of hand function to the patient with RA (Jones et al., 1991), it
      should also be admitted that there is little research evidence relating to the
      conservative management of hand function in this patient population. This paper
      reviews the research that has been carried out in this area and explores possible
      areas for further research.

PMID- 17041967
TI  - An exploration of patients' experiences of anti-TNF therapy.
AB  - OBJECTIVE: To explore the experience of rheumatoid arthritis patients receiving
      anti-tumour necrosis factor (anti-TNF) therapy on physical, psychological and
      social well-being. METHOD: Seven patients with rheumatoid arthritis (RA) who
      received six months of infliximab were interviewed in depth by one researcher to
      identify their experiences of this treatment. The interviews were tape-recorded
      and analysed using Colaizzi's procedural steps. RESULTS: Four main categories
      were identified from the interview relating to the patient's experience of anti
      TNF therapy. These included: The impact of living with RA on physical,
      psychological and social function. The influence of anti-TNF therapy on physical,
      psychological and social function. The experience of attending for treatment. The
      impact of discontinuing anti-TNF treatment. CONCLUSION: All seven patients
      experienced benefits from receiving anti-TNF therapy. These benefits were not
      maintained once the treatment period was completed.

PMID- 17041968
TI  - Biologic agents used to treat rheumatoid arthritis and their relevance to
      podiatrists: a practice update.
AB  - This review considers the pharmacological management of rheumatoid arthritis
      including the role of anti-tumour necrosis factor alpha (TNFalpha) agents, as a
      precursor to highlighting some of the issues for podiatrists involved in the care
      of patients on this particular medication.

PMID- 17041969
TI  - Should nurses be screening for ischaemic heart disease in nurse-led rheumatoid
      arthritis clinics?

PMID- 17041970
TI  - Nurse prescribing in rheumatology: a case study.
AB  - This case study outlines the clinical management, and in particular the drug
      management, of a patient with polymyalgia rheumatica (PMR) in secondary care. The
      lady in question, Mrs Adams (pseudonym as per NMC Guidelines), is under the care
      of the consultant rheumatologist. Within this clinical setting, and in
      conjunction with an appropriate, agreed clinical management plan, this paper
      demonstrates that the nurse consultant can effectively manage Mrs Adams' care and
      treatment.

PMID- 17041971
TI  - Practice development: an important component of the clinical nurse specialist
      role.

PMID- 17041972
TI  - Pain mechanisms and the rheumatic diseases.
AB  - Pain is the predominant complaint of those with a rheumatological condition. This
      paper provides a broad overview of the current theories on the mechanisms of
      pain, the structure of the nervous system, and how these may relate to the
      sometimes seemingly incomprehensible symptoms of pain and other sensory
      disturbances that some rheumatology patients describe. Three case histories
      relating to rheumatoid arthritis, osteoarthritis and fibromyalgia are used to
      illustrate how this knowledge can be applied to clinical practice.

PMID- 17041973
TI  - Drug treatment for fibromyalgia.
AB  - The term 'fibromyalgia' probably covers a variety of diagnoses for which we have
      no formal diagnostic tests. Nevertheless, it remains a cause of discomfort and
      disability, often amenable to non-drug treatment that should always be tried
      first. This article reviews the different drug treatments available that are of
      interest to the rheumatology community because the drugs that often procure pain
      relief are not always the same as those that are conventionally used for
      degenerative or inflammatory polyarthritis. This, in turn, may provide a clue to
      causation.

PMID- 17041975
TI  - Towards multidisciplinary teamworking in musculoskeletal care: evolution of a
      service.

PMID- 17041974
TI  - Occupational balance of women with rheumatoid arthritis: a qualitative study.
AB  - OBJECTIVE: Occupational balance has been shown to be an important factor in
      maintaining health. Rheumatoid arthritis (RA) reduces functional ability and
      quality of life and may thus reduce occupational balance. The aim of this
      qualitative pilot study was to explore occupational balance in women who have RA.
      METHODS: Nine women with RA with past, but not current, paid work experience, no
      other confounding neuro-motor disease and with disease duration of 0.75-31 years
      were selected from an Austrian rheumatology outpatient clinic. Age range of the
      participants was 28-68 years. A semi-structured interview was conducted with each
      participant and transcribed verbatim. Data were analysed by the constant
      comparative method from an occupational perspective. RESULTS: Three main
      categories emerged: (1) The participants experienced a process of change that
      affected their occupational balance. (2) This new state of occupational balance
      was characterized by changed levels of involvement in physical, mental, social
      and rest occupations and by a certain level of unpredictability of symptoms. (3)
      Overall, the new state of occupational balance was valued differently:
      positively, indifferently or negatively. CONCLUSION: RA was found to have a
      considerable impact on occupational balance. The experience is not invariably
      seen as negative as previous literature would suggest. Further research should
      explore the longitudinal dimension of occupational balance in people with RA.

PMID- 17041976
TI  - Rheumatology telephone advice lines.

PMID- 17041977
TI  - Cannulation: professional needs and patient experiences.

PMID- 17041978
TI  - Rehabilitation in rheumatoid arthritis: a critical review.
AB  - This article considers the evidence for effectiveness and timing of
      rehabilitation for people with rheumatoid arthritis (RA). The Cochrane Library,
      DARE, Medline, Embase, CINAHL and AMED were searched to identify systematic
      reviews and randomized controlled trials evaluating rehabilitation interventions
      for people with rheumatoid arthritis. Many trials identified had methodological
      limitations (e.g. short follow-up periods, small sample sizes). Evidence to date
      is that symptomatic relief results from thermotherapy, laser therapy, acupuncture
      and assistive devices. In the short-term, comprehensive occupational therapy (in
      established rheumatoid arthritis), orthoses, and mind-body approaches can help
      maintain function. Over at least a one-year period, the following are effective
      in reducing pain and maintaining function: patient education and joint protection
      training using behavioural approaches; dynamic exercise therapy, hand exercises
      and hydrotherapy; and cognitive-behavioural therapy (in people with poorer
      psychological status). Many trials have recruited people with moderate to severe,
      established RA and relatively little is known about the long-term effectiveness
      of early rehabilitation, although this is becoming much more common in practice.
      Despite the increased availability of guidelines and systematic reviews, most
      conclude there is insufficient evidence for many areas of rheumatology
      rehabilitation. Further well-designed clinical trials are needed recruiting
      people with early disease using patient-centred outcomes.

PMID- 17041979
TI  - Long-term influences of a biopsychosocial rehabilitation programme for chronic
      pain patients.
AB  - OBJECTIVE: Chronic pain leads to high costs in the form of compensation for
      absence from work due to illness, production loss and health care utilization.
      Multidisciplinary treatment programmes at pain clinics can result in return to
      work and a decrease in doctor visits. The aim of this study was to evaluate the
      long-term influences of a rehabilitation programme in primary health care for
      chronic pain patients with regard to doctor visits, frequency of sick-leave and
      level of disability. DESIGN: A longitudinal, intervention study design was used
      over a three-year period. METHODS: A biopsychosocial rehabilitation programme
      based on ego-strengthening psychotherapy was used. An occupational therapist and
      a physiotherapist led the intervention, which comprised two meetings per week for
      six weeks. The study was performed in a primary health care area in the southwest
      of Sweden with 54 chronic pain patients. RESULTS: The results showed a
      significant decrease in the number of doctor visits as well as sick-leave days.
      The level of absenteeism due to occupational disability changed significantly
      from being on sick leave to receiving a disability pension. CONCLUSIONS: The
      rehabilitation programme reduced patient attendance at health care facilities but
      did not increase the numbers of patients returning to work.

PMID- 17041980
TI  - Patients' perspectives on self-management following a back rehabilitation
      programme.
AB  - OBJECTIVE: The management of chronic low back pain (CLBP) is becoming
      increasingly demanding upon health care services and society. Programmes
      combining exercise, education and a biopsychosocial approach have become a
      popular way of managing CLBP. Programmes are designed to change behaviour,
      increase activity levels and encourage self-management. Patients' experiences of
      attending a back rehabilitation programme were examined. METHODS: This study used
      a qualitative approach combining interviews, non-participant observation and
      evaluation of documentation to establish the patients' perspective of self
      management following a back programme. RESULTS: All the patients (n = 6 )
      indicated they were self-managing by continuing to exercise and utilizing the
      advice given after attendance. Two patients felt they should continue attending
      the therapy department to exercise in order to gain benefit, demonstrating
      reliance on continued health care support. Obstacles to continuing with exercise
      were cited as pain, time, and family constraints. Patients also expressed
      limitations following attendance regarding the type and level of activity their
      CLBP would allow them to manage. The data suggested activity limitation was
      inadvertently reinforced by the therapists during the sessions, in the programme
      letter and by the patients' existing beliefs regarding the cause of their CLBP.
      CONCLUSION: The study demonstrated the importance of understanding patients'
      beliefs and expectations prior to a back programme and accounting for these
      during attendance. This study also highlighted that all heath care professionals
      should be aware of the impact of the language and terminology used when working
      with CLBP patients.

PMID- 17041981
TI  - Complex interventions.

PMID- 17041982
TI  - Ankylosing spondylitis: clinical update.

PMID- 17041983
TI  - The role of social comparison in coping with rheumatoid arthritis: an interview
      study.
AB  - OBJECTIVE: This study aimed to explore the effects of participants' perceptions
      of support, ways of coping and feelings of control, on their accounts of well
      being. METHODS: Semi-structured interviews were conducted with 10 patients with
      rheumatoid arthritis (RA) and explored the dynamics of participants' accounts of
      coping with their everyday lives. RESULTS: Four categories of coping mechanisms
      were evident in all participants' accounts: support during the medical
      consultation, nurse support, social support, and comparative strategies. This
      paper focuses on just one of the themes that emerged from our analysis. Further
      insight into coping mechanisms was provided by the prevalence of comparative
      coping strategies. A comparison with previous disease states was used by every
      participant. This comparison enhanced their sense of control and fostered a sense
      of well-being. Social comparison was used by seven participants to show
      themselves how fortunate they were in relation to others with RA. CONCLUSION:
      Comparative coping has been identified as an important strategy adopted by these
      participants that could be explored in further intervention-based studies of
      coping.

PMID- 17041984
TI  - The impact of group education on participants' management of their disease in
      lupus and scleroderma.
AB  - OBJECTIVES: The aim of this study was to investigate the impact of the pilot
      education programmes, entitled 'Focus on Lupus' and 'Focus on Scleroderma', upon
      participants' management of their disease. METHODS: Five people with lupus and
      five with scleroderma were invited to take part in individual semi-structured
      interviews. Qualitative analysis of transcripts was performed using a framework
      approach. Views relating to changes in knowledge and behaviour, increased
      empowerment, meeting others and the format and delivery of the programmes were
      explored. RESULTS: Analysis of the interviews revealed overall satisfaction with
      both programmes, however people with lupus had more positive feelings about their
      attendance. Both disease groups considered it valuable to meet others with the
      same disease and welcomed the involvement of a patient educator within the
      programme planning team. The main difference between the two groups concerned
      behaviour change. The lupus group revealed more definite life changes.
      Participants unanimously regarded the format of the programme highly and most
      were satisfied with the content.

PMID- 17041985
TI  - An introduction to medical statistics for health care professionals: describing
      and presenting data.
AB  - This article is the first in a series of three that will give health care
      professionals a sound and helpful introduction to medical statistics. This
      article covers three main areas: description of the different types of data
      available, appropriate summary measures used to describe different data types,
      and methods used to present these data.

PMID- 17041986
TI  - The development of a user-led clinical service for newly diagnosed rheumatoid
      arthritis patients. An action research study.
AB  - OBJECTIVE: To identify the clinical services required to meet the perceived needs
      of patients within the first 6-12 months following a diagnosis of rheumatoid
      arthritis in an orthopaedic NHS trust. METHODS: An action research methodology
      was utilized. Twenty three newly diagnosed patients were asked to complete a
      questionnaire focusing on their needs at the time of diagnosis. The content
      included reactions to diagnosis, physical and psychological implications and
      clinical services that were required. A sub-sample of patients (n = 6)
      participated in an interview to explore these issues in more depth. A
      questionnaire was also distributed to 14 members of the multidisciplinary team
      (MDT) to ascertain their views on the purpose, content, and provision of a
      clinical service for newly diagnosed patients. RESULTS: Eighteen patients agreed
      to take part (M:F, 9:9, age range 23-74 years, mean age 52.3 years, mean disease
      duration from diagnosis 16 weeks). Data from the questionnaires and interviews
      led to the following themes being identified: pre-diagnosis anxiety and fear, the
      impact of the diagnosis, physical and psychological implications of the
      diagnosis, and issues related to control perceptions. There was concordance
      between the MDT and the patients regarding impact of the disease and the need for
      information. Areas of the service that were identified independently by patients
      related to the importance of the period of time pre-diagnosis while awaiting the
      hospital appointment, and employment issues. CONCLUSIONS: This study has
      identified the impact of RA in the early stages of pre- and post- diagnosis on
      physical, psychological and social functioning and has consequently informed
      service development.

PMID- 17041987
TI  - The Early Rheumatoid Arthritis Network (ERAN).

PMID- 17041988
TI  - Long-term observational studies in rheumatoid arthritis: a valuable resource for
      clinicians and health professionals.

PMID- 17041989
TI  - Clinical and psychological outcomes of patient education in rheumatoid arthritis.
AB  - OBJECTIVE: Evidence that patient education improves outcome in self-selected
      patients is often based on studies using patients with a mixture of diagnoses
      (primarily osteoarthritis) and where the education is delivered in a community
      setting. This study explored whether hospital outpatients with rheumatoid
      arthritis (RA) who were offered a self-management programme showed a similar
      response. METHODS: A randomized controlled trial was undertaken of either
      observation or observation plus an educational intervention of five sessions
      (12.5 hours) designed to enhance self-management. Pain and self-efficacy for pain
      were the primary outcome measures. These and other standardized assessments were
      made at 0, 4, 8 and 36 weeks for a variety of psychological and disease states.
      Knowledge of RA and its treatment was measured at 0 and 4 weeks using a multiple
      choice questionnaire. RESULTS: Sixty-eight of 79 randomized patients provided
      adequate data. In those randomized to be offered education, knowledge of RA and
      its treatment increased by 18% compared to 9% in controls (p = 0.058). Self
      efficacy for pain improved between weeks 0 and 4 by 10.3% (p = 0.015) in those
      offered education, and by 14.1% in those who were offered and accepted education
      (p = 0.001) but the difference from controls was not maintained after four weeks.
      There were no significant differences between groups in pain or in any of the
      remaining variables. Most patients reported that the education had been helpful.
      CONCLUSIONS: Patients offered education gained knowledge and reported personal
      benefit, but only improved in self-efficacy for pain and only for a short time.
      RA patients drawn from hospital outpatient clinics and allocated to an
      educational intervention may not gain changes in health status as measured by the
      instruments employed in this study.

PMID- 17041991
TI  - Fife Rheumatic Diseases Unit 10 years on: a personal perspective.
AB  - May 2004 marked the 10th anniversary of the Fife Rheumatic Diseases Unit (FRDU)
      based at the Sir George Sharp Unit, Cameron Hospital in Fife. This article aims
      to share with the reader FRDU's particular model of service delivery, how FRDU,
      and the occupational therapy service in particular, has evolved over the past 10
      years.

PMID- 17041990
TI  - Within-day reliability of temporal-spatial gait parameters associated with
      rheumatoid arthritic feet.
AB  - OBJECTIVE: To determine whether the GAITRite system can reliably measure temporal
      and spatial gait parameters in patients with rheumatoid arthritic feet. METHODS:
      Fifty patients diagnosed with rheumatoid arthritis were each measured on two
      separate occasions on the same outpatient visit. Temporal and spatial gait
      parameter readings were recorded for each of three walks across the GAITRite mat.
      Intraclass correlations (2,1) in combination with within-subject standard
      deviation were used to quantify within-day reliability. RESULTS: The intraclass
      correlation, ranging from 0.75 to 0.87, demonstrated excellent within-day
      repeatability for walking speed, cadence, step length and stride length. Good
      reliability was reported with cycle time (0.74) and base of support (0.62).
      Within-subject standard deviation allows these to be used in a clinical setting.
      CONCLUSION: The within-day reliability of temporal and spatial gait parameters in
      rheumatoid arthritic patients has been demonstrated in the current study.
      However, further investigation of between-day reliability is necessary and would
      provide clinicians with reliable data in the objective assessment and any form of
      intervention in rheumatoid arthritis patients.

PMID- 17041992
TI  - Internet information on rheumatoid arthritis: an evaluation.
AB  - OBJECTIVE: To evaluate the quality of internet information, readily accessible by
      the public, relating to rheumatoid arthritis and to investigate the relationship
      between financial interests of websites and the quality of information provided.
      METHODS: Five well-known search engines on the internet were investigated in an
      attempt to replicate a search undertaken by a typical patient. The phrase
      'rheumatoid arthritis' was used for each search and the first 20 results were
      evaluated. Each site was evaluated in terms of 'general website criteria' and
      'specific criteria' in relation to rheumatoid arthritis. The websites were scored
      out of 30. RESULTS: Fifty-five websites were evaluated. The mean total quality
      score was 12.15 (SD = 6.53) and 40 sites (72.7%) scored < 50% of the total marks
      available. Information about authorship, ownership and currency were missing in
      more than 75% (n = 42) of cases; only 20% (n = 11) of sites gave clear references
      to scientific literature; 64% (n = 35) of sites were judged to have a financial
      interest and these scored significantly lower total quality scores compared to
      the informative sites (p = <0.01). Information about the role of physiotherapy in
      the management of rheumatoid arthritis was absent in 70.9% (n = 39). CONCLUSION:
      The internet is a poor source of information for rheumatoid arthritis patients.
      Quality information is scarce and finding it is time-consuming. Guidelines are
      needed to regulate information that is published on the internet and define who
      is eligible to publish it. Until then the internet should not be recommended as a
      single source of patient information unless professionally endorsed websites are
      recommended.

PMID- 17041993
TI  - An exploratory survey of the practice of rheumatology nurses addressing the
      sexuality of patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic progressive inflammatory
      condition primarily affecting the joints. It is characterized by pain, stiffness
      and fatigue. Research has demonstrated that the symptoms of RA can negatively
      impact on a patient's sexuality and patients would welcome the opportunity to
      discuss their sexual needs with a health professional. AIMS: To identify current
      perceived practice, skills, and knowledge of rheumatology nurses in addressing
      the sexuality of patients with RA. METHODS: A postal questionnaire was sent to
      132 rheumatology nurses identified from the British Health Professionals in
      Rheumatology Handbook. The questionnaire sought to identify the nurse's role in
      the assessment and management of RA patients' sexuality. RESULTS: Seventy six
      questionnaires were returned (response rate of 57.5%). Sixty nine respondents
      stated that sexuality should be included within the nursing assessment. The main
      factors that influenced whether sexuality was discussed was privacy, the level of
      knowledge and skills and time. Nurses felt that while contraceptive advice for
      patients treated with cytotoxic drugs was discussed in depth, the patient's
      sexual relationship was not discussed at all. The majority of respondents (83%)
      had never received any training in this area and would undergo training if they
      had the opportunity. CONCLUSION: While rheumatology nurses acknowledge the
      importance of including sexuality in the care management of patients with RA, in
      practice the impact of the condition on a patient's sexuality is only discussed
      briefly. Rheumatology nurses have identified the need for further training in
      this complex area.

PMID- 17041994
TI  - Addressing psychological and social issues of rheumatoid arthritis within the
      consultation: a case report.

PMID- 17041995
TI  - Adherence with drug therapy in the rheumatic diseases Part one: a review of
      adherence rates.
AB  - Drug therapy plays a major role in the management of many rheumatic diseases and
      is particularly important in rheumatoid arthritis (RA) because of the significant
      rates of morbidity and mortality (Pincus, 1995). Understanding of the
      pathogenesis of RA has led to the development of new and more effective drugs
      (Emery et al., 1999), but the ultimate efficacy of any drug therapy depends upon
      the patient's decision to take it. There is widespread agreement that many people
      with rheumatic disease do not adhere to their medication regimens (Deyo et al.,
      1981; Belcon et al., 1984; Pullar et al., 1988; Hill et al., 2001). Research has
      demonstrated that 50% of women taking hormone replacement therapy for the
      prevention of osteoporosis discontinue treatment after a year (Fordham, 2000) and
      similar rates of discontinuation are found in other chronic diseases (Haynes et
      al., 1996, 2000). This is bewildering as, in asymptomatic illnesses such as
      hypertension and diabetes, the expectation is that levels of adherence would be
      lower than in diseases where pain and stiffness are present. The picture becomes
      even more confusing when we consider the findings from a recent multi-country
      study of RA, which found no association between adherence and disease severity,
      nor with the treatment prescribed (Viller et al., 1999). In chronic disease poor
      adherence is commonplace. The World Health Organization (WHO) recognizes this and
      has recently stated that 'poor adherence to treatment of chronic diseases is a
      worldwide problem of striking magnitude' and cites adherence to long-term therapy
      for chronic illnesses in developed countries averaging just 50% (WHO, 2003). The
      first part of this two part review focuses on adherence with drug therapy, and
      the second part discusses different methods of measuring it.

PMID- 17041996
TI  - How people with rheumatoid arthritis perceive leisure activities: a qualitative
      study.
AB  - OBJECTIVE: To explore how people with rheumatoid arthritis (RA) perceive leisure
      activities. METHOD: A phenomenographic approach using semi-structured interviews
      to explore the impact of RA on leisure pursuits was used. RESULTS: Three
      descriptive categories containing 11 conceptions emerged: (1) Experiencing
      constraints included four conceptions: seeing limitations, needing time, finding
      balance, being dependent. (2) Experiencing coherence included four conceptions:
      accepting feelings participating in a social context, being active, having
      insight. (3) Finding solutions included three conceptions: choosing, planning,
      and adapting. CONCLUSIONS: This study emphasizes the limited choices and problems
      people with RA had participating in leisure activities, as well as its impact on
      self-esteem.

PMID- 17041997
TI  - Static orthoses in the prevention of hand dysfunction in rheumatoid arthritis: a
      review of the literature.
AB  - Static orthoses are recommended for individuals who have early rheumatoid
      arthritis (Scottish Intercollegiate Guidelines Network, 2002; College of
      Occupational Therapists, 2003). These orthoses aim to rest and immobilize
      weakened joint structures and decrease local inflammation (Janssen et al., 1990;
      Nicholas et al., 1982); correctly position joints (Nordenskiold, 1990; Ouellette,
      1991); minimize joint contractures (McClure et al., 1994); increase joint
      stability (Kjeken et al., 1995); relieve pain (Feinberg, 1992; Callinan and
      Mathiowetz, 1996; Kjeken et al., 1995) and improve function (Janssen et al.,
      1990; Pagnotta et al., 1998; Nordenskiold, 1990). Wrist and hand orthoses have
      been routinely prescribed for individuals with rheumatoid arthritis (RA) for the
      last 30 years with limited evidence that they are effective in achieving their
      purported aims. This article reviews the possible deterioration in hand structure
      that can occur in RA and discusses the theoretical basis for the application of
      static orthoses in RA. The evidence for the effectiveness of four commonly used
      static orthoses is then examined.

PMID- 17041998
TI  - An introduction to medical statistics for health care professionals: Hypothesis
      tests and estimation.
AB  - This article is the second in a series of three that will give health care
      professionals (HCPs) a sound introduction to medical statistics (Thomas, 2004).
      The objective of research is to find out about the population at large. However,
      it is generally not possible to study the whole of the population and research
      questions are addressed in an appropriate study sample. The next crucial step is
      then to use the information from the sample of individuals to make statements
      about the wider population of like individuals. This procedure of drawing
      conclusions about the population, based on study data, is known as inferential
      statistics. The findings from the study give us the best estimate of what is true
      for the relevant population, given the sample is representative of the
      population. It is important to consider how accurate this best estimate is, based
      on a single sample, when compared to the unknown population figure. Any
      difference between the observed sample result and the population characteristic
      is termed the sampling error. This article will cover the two main forms of
      statistical inference (hypothesis tests and estimation) along with issues that
      need to be addressed when considering the implications of the study results.

PMID- 17041999
TI  - Patients as teachers: a new approach to patient involvement.
AB  - Patients as Teachers is an approach to patient involvement which involves
      bringing together a key sub-group for a speciality with a facilitator to focus on
      particular aspects of the service. This approach was used by the rheumatology
      team in Bradford to elicit feedback from South Asian women for whom English is
      not the first language. The focus groups generated constructive feedback about
      issues relating to, the hospital environment, information giving and service
      provision. This was fed back to clinicians at an educational meeting attended by
      lay representatives, and agreed actions were determined. Progress made on the
      recommendations was evaluated at six months.

PMID- 17042001
TI  - The updated BSR guidelines for anti-TNF in adults with RA: what has changed and
      why?
AB  - In 2001 the British Society for Rheumatology (BSR) published guidelines for
      prescribing TNF-alphablockers in adults with rheumatoid arthritis (RA). In an
      unusual move, the National Institute of Clinical Excellence (NICE) accepted the
      BSR guidelines and published them unchanged and included them in their own
      Technology Appraisal (National Institute of Clinical Excellence, 2002). The field
      of anti-TNF in RA is rapidly changing, and the BSR Standards, Guidelines and
      Audit Working Group decided in 2004 to update the guidelines. These were
      published in February 2005 (Ledingham and Deighton, 2005). This article
      summarizes the key changes, and attempts to justify them, using further data that
      has emerged since the updated guidelines were produced, and audit data from the
      Derby Rheumatology department.

PMID- 17042003
TI  - Adherence with drug therapy in the rheumatic diseases Part two: measuring and
      improving adherence.
AB  - Part one of this review highlighted the problem of high rates of non-adherence
      with drug therapy in the rheumatic diseases. Part two addresses the problem of
      assessing adherence to drug therapy, focuses on factors affecting medication
      taking and discusses interventions that can help to improved adherence.

PMID- 17042002
TI  - Outcomes generated by patients with rheumatoid arthritis: how important are they?
AB  - BACKGROUND: It has been shown previously that patients with rheumatoid arthritis
      (RA) can generate a wide range of outcomes that they consider important in
      treatment. It is not known if these outcomes are generally important in the wider
      RA patient community. OBJECTIVES: (1) To examine whether recent patient-generated
      outcomes are generalizable within a wider RA population; (2) to assess the
      relative importance of each outcome; and(3) to explore whether any important
      outcomes have been omitted. METHODS: A questionnaire, listing 23 outcomes
      previously generated by RA patients, was distributed through three rheumatology
      centres in the UK. Patients gave an importance score to each outcome (0-3),
      selected their top three most important outcomes, and then listed any outcomes of
      personal importance that were missing. RESULTS: 323 questionnaires were returned
      (65%). All outcomes were deemed important. Independence, pain, and mobility were
      most frequently selected by patients in their top three outcomes but were not
      chosen by 61-66% of patients. The next most commonly chosen outcomes related to
      feeling well and fatigue. Factor analysis revealed six reasonably distinct
      groupings: general well-being (11.9% explained variance), day-to-day
      functioning(10.6%), emotional and psychological well-being (10.6%), social role
      and confidence (10%), physical symptoms (9.5%) and medication issues (7.9%).
      CONCLUSION: Outcomes generated by patients as important in RA, are generalizable
      and inclusive. The most important (independence, pain and mobility) are routinely
      treated and measured. The next most important (feeling well, fatigue) are
      infrequently addressed and deserve urgent consideration for measurement,
      treatment and research.

PMID- 17042004
TI  - Perception of tactile massage as a complement to other forms of pain relief in
      rheumatic disease.
AB  - OBJECTIVE: To investigate how patients with rheumatic disease perceive tactile
      massage as a complement to other pain alleviation methods. METHODS: A
      phenomenographic approach with semi-structured interviews was employed on a
      strategic sample of 14 patients with various rheumatic diseases, both
      inflammatory and non-inflammatory, who had been admitted to Spenshult Rheumatic
      Hospital. RESULTS: Three descriptive categories with a total of nine conceptions
      emerged. The descriptive categories were: experiencing alleviation, experiencing
      trust, and gaining insight. Experiencing alleviation described how patients
      experience relaxation, pleasure and respite. Experiencing trust described how
      patients experience a sense of security, confirmation and inner peace. Gaining
      insight described how patients get to know themselves, see possibilities, and
      experience wholeness. CONCLUSIONS: When caring for patients who have a chronic
      illness involving considerable changes to their lives, it is important for health
      professionals not only to be aware of their physical needs but also to take
      account of the whole person. This study demonstrates the importance of offering
      patients a complement to conventional treatment. Tactile massage is a method that
      promotes a holistic view of patients with chronic pain as well as allowing them
      to find a new focus in terms of the disease and how they cope with it in their
      daily lives.

PMID- 17042005
TI  - Providing specialist clinical skills in soft tissue and intra-articular injection
      through a postgraduate masters module.
AB  - Current philosophy and policy changes in the National Health Service are
      encouraging healthcare practitioners to extend their clinical skills to create a
      more patient-centred approach thus allowing patients to be seen in a timely and
      more appropriate manner. This often requires further development of the
      practitioners' skills and knowledge. One approach to achieve this is through
      collaboration between employers and educational providers to ensure that
      educational experience is not only evidence based but also responsive to the
      needs of the current and future workforce. A postgraduate module was developed to
      raise critical and evaluative skills, as well as the technical skills of
      practitioners using injections in the management of joint and soft tissue
      pathology, while developing a professional responsibility towards injection
      practice. The module emphasized learning though experience by contextualizing the
      theoretical aspects of the module and by its student centred assessments. Further
      strengths of this module are that it has utilized academic and clinical expertise
      and knowledge to enable clinicians to gain additional skills and the
      multidisciplinary approach engendered good working practice Overall the module
      was evaluated positively by both tutors and students and not only met its aims
      but also addressed the current professional and policy issues around continuing
      professional development.

PMID- 17042006
TI  - Prescribing and injecting: the expanding role of the rheumatology nurse.

PMID- 17042007
TI  - How effective is physiotherapy in the treatment of complex regional pain syndrome
      type I? A review of the literature.
AB  - Complex regional pain syndrome (CRPS) is a debilitating pain disorder for which
      patients commonly receive physiotherapy. The objective of this literature review
      is to assess how effective physiotherapy is in the management of adult and
      childhood CRPS type I. An electronic literature search was performed of the
      databases AMED, Cinahl, Embase, Ovid Medline, Pubmed, PEDro and PsycINFO, from
      their inception to November 2004. Human subjects clinical trials, written in
      English, which could assist in answering the research question were included.
      Twenty-five (of 748) papers met the inclusion criteria and were reviewed. The
      review suggests that exercise, motor imagery and mirror feedback exercises,
      relaxation techniques, acupuncture, electroacupuncture, transcutaneous nerve
      stimulation and combined treatment programmes may help in the treatment of CRPS
      type I. However, since numerous methodological weaknesses (e.g. small sample
      sizes, not employing control groups, not evaluating findings against statistical
      tests) littered the limited literature, it was not possible to determine the
      effectiveness of individual treatments. Recommendations are made to develop the
      evidence base.

PMID- 17042008
TI  - An introduction to medical statistics for health care professionals: basic
      statistical tests.
AB  - This article, the third and final article in the series, aims to give health care
      professionals (HCPs) a sound and helpful introduction to medical statistics
      (Thomas, 2004, 2005). A brief summary of the content of the previous articles is
      given in Table 1. The current article will cover the area of basic statistical
      tests with the aim of guiding HCPs to the correct test for a particular research
      question and dataset. The article will not go into great depth of the formal
      methods of calculation required for all the tests covered but I would suggest
      that the reader refer to standard textbooks (Jordan et al., 1998; Swinscow, 1998;
      Altman, 1994; Bland, 2000), the help sections of statistical packages (SPSS or
      Stata), or consult a statistician. For ease of reference within the article the
      tests have been grouped by the data type, i.e. numerical or categorical. Further
      separation within each data type has been carried out depending on the number of
      groups being compared, whether the groups are independent, the size of the
      sample, and, in the case of numerical data, the distribution of the variable. For
      quick reference, two other tables are also presented which summarize which
      analysis methods should be used in each situation.

PMID- 17042009
TI  - Patients' perceptions of drug dispensing in a rheumatological in-patient unit.
AB  - INTRODUCTION: The dispensing of drugs in medical care systems is, in most
      countries, strictly regulated, and nurses are responsible for distributing drugs
      to in-patients. AIM: To describe the perceptions of patients with rheumatic
      diseases regarding traditional drug dispensing during in-patient care and
      rehabilitation in a specialized rheumatological care unit. METHOD: Twenty in
      patients who stayed in the Spenshult Hospital unit for 3-4 weeks and who were on
      continuous medication were chosen for the study. The phenomenographic approach
      was used for the collection and analysis of data. FINDINGS: Three descriptive
      categories emerged - Relief, Active Participation and Dependence. These
      descriptive categories comprised: three perceptions for Relief (to experience
      security, to be 'served', to dare to bother), two for Active Participation (to
      rely on one's own ability, to search for knowledge) and two for Dependence (lack
      of independence, lack of information). CONCLUSION: The patients experienced
      relief due to the nurse assuming responsibility for the medication and its
      dispensation. Patients expressed a wish to be more active in the management of
      their medication, as they trusted their own ability. The patients articulated
      that they were dependent on the nurse to give them the correct medication and
      they also asked for more information about their medication.

PMID- 17042010
TI  - Paracetamol use in musculoskeletal pain: an audit of use and patient perceptions
      of paracetamol as an effective analgesic.
AB  - Musculoskeletal pain is a complex problem with often very detrimental
      consequences which affects a high proportion of the general population. Health
      care professionals, when prescribing for musculoskeletal pain, often overlook
      simple analgesia. Patient perceptions of analgesia may vary to those of health
      care professionals, and in part affect the use of simple analgesia for
      musculoskeletal pain. This paper describes an audit of paracetamol use and
      patient perceptions of paracetamol as an effective analgesic agent, in 113
      patients attending a musculoskeletal pain outpatient clinic in a university
      teaching hospital. The audit has helped prompt the development of a multi
      disciplinary strategy to achieve optimum management.

PMID- 17042011
TI  - An evaluation of nurse-led rheumatology telephone clinics.
AB  - AIMS AND OBJECTIVES: The aim of the study was to examine the impact on waiting
      times and patient satisfaction of nurse-led rheumatology telephone clinics.
      METHODS: Patients awaiting outpatient review were contacted by the rheumatology
      clerk and offered a nurse-led rheumatology telephone appointment. Those who
      accepted were given a date and time for the appointment. A telephone consultation
      proforma was used to structure the call and to organize appropriate
      investigations/action. A questionnaire was mailed to the 68 patients reviewed
      during the first month of the telephone clinics to assess satisfaction. Status
      forms were also completed to record further action. RESULTS: Of the 68 patients
      surveyed 73% completed and returned the questionnaire. Overall 72% were happy
      with the telephone consultation and would be happy to use the service again.
      Waiting times were reduced by two months as a total of 169 patients were reviewed
      during the April to August period. CONCLUSION: Nurse-led telephone consultation,
      as part of chronic disease management, can be extremely beneficial for all
      rheumatology patients as a high level of satisfaction was achieved. In addition
      telephone consultations have helped to reduce the follow-up waiting times within
      the department by two months. This audit shows that telephone appointments
      conducted by an experienced nurse using an assessment proforma can be
      incorporated into routine follow-up care.

PMID- 17042012
TI  - High disease activity scores predict the need for additional health services in
      patients over 60 with rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether we meet perceived need, in terms of appropriate
      supportive health services (physiotherapy, occupational therapy, chiropody and
      footwear, surgery, education and information), of patients aged 60 years and over
      with rheumatoid arthritis (RA). DESIGN: A cross-sectional survey. PARTICIPANTS:
      123 patients attending rheumatology outpatient clinics. RESULTS: The response
      rate was 82% (99/123). Of the respondents 78% had one or more perceived needs.
      Respondents were more likely to express a need for chiropody or footwear (46%),
      education about RA (29%), or physiotherapy (22%) than for occupational therapy
      (7%) or surgery (6%). Further analysis compared this group with the 'non-needy'
      group. There was a correlation between high disease activity scores and high
      anxiety scores and greater perceived need for additional health services.
      CONCLUSION: There was significant unmet demand for chiropody and footwear,
      education about RA, physiotherapy, occupational therapy and surgery. It is
      possible that strategies to reduce anxiety and improve control of active
      inflammatory disease may reduce demand for supportive services in certain
      patients.

PMID- 17042013
TI  - Measuring sensation in the feet of patients with rheumatoid arthritis.
AB  - OBJECTIVES: (1) To determine the test-retest reliability of monofilaments pressed
      against the skin as a method of assessing sensation in the feet of patients with
      rheumatoid arthritis (RA) and in controls using two grades of monofilaments; (2)
      to determine the stability of findings over 6 weeks; and (3) to calculate initial
      estimates of frequency of loss of sensation and to investigate its association
      with disease status. METHOD: Clinical examination of the feet was undertaken in
      51 patients with RA and 20 normal controls. Six sites on each foot were tested
      twice with both 10 g and 3 g research grade monofilaments and this was repeated
      after 6 weeks. Disease status was measured using the Disease Activity Score, the
      Health Assessment Questionnaire, visual analogue scales of pain, and the acute
      phase response using erythrocyte sedimentation rate and plasma viscosity.
      RESULTS: Reproducibility was high for 3 g (kappa=0.73) and 10 g (kappa=0.75)
      monofilaments. The best balance between sensitivity (58.8%) and specificity
      (87.5%) for distinguishing the feet of patients from the feet of controls was
      using the 3 g filament and defining reduced protective sensation as being
      sensitive to less than 11 of 12 applications. Using this definition, the
      prevalence of reduced protective sensation is 59% in the patient group and 12.5%
      in the feet of controls. There was some variation in sensation over 6 weeks in
      the patient group, but this was not related to measures of clinical status.
      CONCLUSION: The use of monofilaments in assessing sensation levels in the RA foot
      is repeatable and reproducible over a six-week period and requires only a short
      time to perform. The frequency of reduced sensation in the feet of patients with
      RA was greater than previously reported. Future studies should assess
      relationships with disease duration and inflammatory status.

PMID- 17042014
TI  - Rheumatology telephone helplines: patient and health professionals' requirements.
AB  - OBJECTIVES: The aim of this study was to ascertain patients' and health
      professionals' requirements from a rheumatology helpline and how such a service
      should be delivered. METHODS: Self-completed questionnaires were administered to
      both users of rheumatology helplines, patients and health professionals (HPs),
      and providers of rheumatology services at five UK NHS trusts. Additional data
      were sought from experts in the field. Information was elicited on access to the
      service, preferred waiting time for response to a call, acceptability of an
      answerphone and choice of HP responding. Quantitative data were analysed using
      percentages and Chi-squared tests. Open questions were analysed as free text
      responses, and organized into clusters of themes. RESULTS: A total of 607
      questionnaires were returned, 523 from users (411 patients, 112 health
      professionals) and 84 from providers. There were no significant differences
      across the five Trusts. The top six reasons for patients contacting the helpline
      were: advice on changes in condition, drug information, understanding symptoms,
      blood results, information on diagnosis, and appointment queries. All groups
      recommended a return call on the same day and were happy to leave an answerphone
      message. HP users requested additional access via e-mail and fax. Rheumatology
      practitioners were deemed the most appropriate personnel to staff a helpline.
      CONCLUSIONS: The findings of this study have contributed a valuable insight into
      the essential components of a rheumatology helpline service from a user and
      provider perspective. These data will add to existing recommendations for the
      management of a rheumatology helpline service and ultimately contribute to a
      proposal for national guidelines.

PMID- 17042015
TI  - Leadership in health care.

PMID- 17042016
TI  - Multiprofessional education for allied health professionals in rheumatology:
      breaking down traditional barriers.

PMID- 17042017
TI  - Patient-reported outcome: Measuring what matters or just another paper exercise?

PMID- 17042018
TI  - Is the drive to manage long-term conditions in the community compatible with
      improving standards of care for those with inflammatory arthritis?
AB  - At the same time as the Government is pushing ahead with its agenda to manage
      long-term conditions in the community, standards of care have been published by
      the Arthritis and Musculoskeletal Alliance (ARMA) in an attempt to improve and
      standardize the care of people with inflammatory arthritis. This raises the
      question of whether the needs and preferences of people with arthritis can be
      adequately met in a primary care setting. This paper looks at the evidence so far
      and discusses the possibilities for achieving ARMA's standards if arthritis care
      is managed in the community.

PMID- 17042019
TI  - Evaluation of the Bristol Royal Infirmary physiotherapy programme for the
      management of patients with osteoarthritis of the knee.
AB  - The aim of this paper is to investigate whether comparable outcomes can be
      achieved when research evidence is translated into clinical practice in the
      management of osteoarthritis (OA) of the knee. An evidence-based physiotherapy
      programme for the management of OA of the knee was established at the Bristol
      Royal Infirmary (BRI). It incorporated both group education and exercise into a
      six week course. Outcomes from the programme were measured using the WOMAC self
      evaluated questionnaire which is sub-divided into pain, stiffness and function
      sections with an additional visual analogue scale (VAS) for pain in each knee.
      Outcomes from the BRI programme were compared with those reported in four papers
      which used similar interventions and evaluation tools. A reduction in pain (VAS)
      of 43% was demonstrated following this programme compared with a mean reduction
      of 16% reported in the other programmes investigated. It is concluded that
      favourable outcomes for patients can be achieved by implementing evidence into
      practice, e.g. in the BRI knee programme.

PMID- 17042020
TI  - Rheumatology nurse practitioners' perceptions of their role.
AB  - OBJECTIVES: To identify the current practices of rheumatology nurse practitioners
      and ascertain their perceptions of how their role could be enhanced. METHOD: A
      cross-sectional questionnaire study of currently employed nurse practitioners in
      rheumatology in the United Kingdom (UK) was undertaken. RESULTS: 200
      questionnaires were distributed and 118 nurses responded. Ninety-five respondents
      met the inclusion criteria for undertaking an advanced nursing role. Typical
      conditions dealt with included: rheumatoid arthritis (96.8%); psoriatic arthritis
      (95.8%); osteoarthritis (63.2%); ankylosing spondylitis (62.8%); systemic lupus
      erythematosus (51.6%); and scleroderma (34.7%). Drug monitoring, education,
      counselling of patients and arranging basic investigations were routinely
      performed by more than 80% of respondents. A smaller proportion performed an
      extended role that included dealing with referrals, research and audit, the
      administration of intra-articular injections, and admission of patients. Specific
      attributes identified as being necessary for competence were: knowledge and
      understanding of rheumatic diseases (48.4%); drug therapy (33.7%); good
      communication skills (35.8%); understanding of the roles of the team (27.4%);
      working effectively (23.2%) as part of a multidisciplinary team; assessment of
      patients by physical examination (28.4%); teaching (26.3%), research (17.9%);
      organizational skills (14.7%); and the interpretation of investigations (9.5%).
      Factors that could enhance their role included: attendance at postgraduate
      courses (30.5%); obtaining further qualifications (13.7%); active participation
      in the delivery of medical education (41.1%); training in practical procedures
      (31.6%); protected time and resources for audit and research (11.6%); formal
      training in counselling (11.6%); and implementation of nurse prescribing (10.5%).
      CONCLUSION: Nurse practitioners already have a wide remit and play an invaluable
      part in the delivery of modern rheumatology services. An extended role could
      improve patient care and enhance nursing career pathways in rheumatology.

PMID- 17042021
TI  - Why do patients with rheumatoid arthritis use complementary therapies?
AB  - OBJECTIVES: (1) to develop an understanding as to how the use of complementary
      therapy (CT) affects a patient's perspective of health and well-being, (2) to
      offer the rheumatology professional insight and understanding as to why a patient
      chooses to use a CT, and (3) to raise awareness as to the forms of CT most
      commonly used by patients with rheumatoid arthritis. METHODS: This qualitative
      study was based on phenomenological principles applied through focused inquiry to
      develop an understanding of the lived experience of the study participants. The
      inclusion criteria of an established diagnosis of rheumatoid arthritis and known
      use of CT were applied to a convenience sample of patients attending a
      rheumatology outpatient department clinic on two consecutive days. Of the 15
      eligible patients identified, five were randomly selected for inclusion in the
      study. Narrative data were collected through analysis of transcripts taken from
      audiotape recordings of unstructured interviews with study participants. A manual
      indexing system was used to develop four significant categorisation themes to
      reflect the findings: (1) incentives to use CT, (2) perceived benefits of CT use,
      (3) the choice of CT used, and (4) perceived disadvantages and risks of CT use.
      RESULTS: Incentives to use CT included dissatisfaction with conventional
      treatment, often in the form of side effects, and drug ineffectiveness. Social
      factors, such as loss of employment and social activities, were also indicated,
      as were psychological changes in the form of depression, hopelessness and fear.
      Perceived benefits were categorised as either physical or psychological with
      associated aspects of choice and control viewed as important elements of personal
      empowerment. The choice of CT used fell into three categories; physical,
      spiritual and herbal. The most commonly used of these were herbal remedies and
      supplements, closely followed by aromatherapy massage. Disadvantages and risks
      were identified as physical (pain and discomfort), psychological (fear and
      uncertainty), and/or material (cost). CONCLUSIONS: This study suggests that
      regular use of CT by patients with rheumatoid arthritis offers holistic benefits.
      Compared to conventional treatments, CT is seen to have advantages in terms of a
      lower incidence of adverse reactions, greater patient choice, psychological
      comfort and an increased quality of the patient/therapist relationship. The use
      of CT by patients with rheumatoid arthritis indicates a need for evidence-based
      information about its use and safety in order to direct practice within a
      rheumatology department.

PMID- 17042022
TI  - Accelerating teamwork: A personal reflection.

PMID- 17042023
TI  - Putting caring into research - the CARE conferences.

PMID- 17042024
TI  - Influences that drive clinical decision-making among rheumatology nurses. Part 1:
      literature review.
AB  - Decisions nurses make while providing patient care to their client group will
      impact on the patient's immediate and long-term outcomes and will also impact on
      service provision. Although many studies have focused on the clinical decision
      making process itself within general nursing areas, little has been published as
      to what factors influence decisions in rheumatology nursing at the clinical
      level. Initial review of the literature suggested the following themes could
      influence decision-making: clinical decision-making, intuition, evidence-based
      practice, experiential learning, knowing the patient, skilled knowledge and
      rheumatology nursing. This article examines the literature surrounding clinical
      decision-making which may influence decision-making within rheumatology nursing
      practice.

PMID- 17042025
TI  - Physiotherapy rehabilitation in patients with massive, irreparable rotator cuff
      tears.
AB  - BACKGROUND: Massive rotator cuff tears provide a challenge for effective
      rehabilitation. Work has been ongoing at Torbay Hospital, Devon since 2000 to
      develop an exercise programme for the management of this patient group. This
      programme has been evaluated in a pilot study and a further randomised controlled
      trial is currently taking place which will enable us to estimate the treatment
      effect. This paper discusses the background to the development of the
      rehabilitation programme, the programme itself and the results of the pilot
      study. The pilot study was an evaluation of the rehabilitation programme.
      OBJECTIVES: This study examined the effectiveness of a physiotherapy regime for
      the treatment of patients with massive rotator cuff tears. METHODS: Patients
      identified through primary and secondary care referrals to physiotherapy with a
      clinical diagnosis of a massive rotator cuff tear underwent an ultrasound scan to
      confirm the diagnosis. A massive cuff tear was one where the leading edge of the
      tear had retracted past the glenoid margin. The clinical diagnosis was based on
      the presence of some or all of the following signs: positive humeral thrust on
      elevation, gross weakness and wasting of supraspinatus and infraspinatus,
      infraspinatus lag and rupture of the long head of biceps. Eligible patients were
      invited to take part in the study and informed consent was obtained. The baseline
      assessment was carried out and then the patient undertook the treatment
      programme. Outcome measures were reassessed 12 weeks from the baseline
      assessment. DESIGN: A cohort study of 10 patients evaluating the change from
      baseline to twelve weeks in the shoulder function of patients undergoing a
      programme of anterior deltoid strengthening and functional rehabilitation. The
      outcome measures used were the Oxford Shoulder Disability Questionnaire (OSDQ)
      and SF36. The OSDQ is validated for use with the UK population and has 12
      questions with 5 point responses. The lowest (best) score is 12 and the highest
      (worse) score is 60. RESULTS: Scores on the OSDQ improved with all patients. The
      mean improvement was 9 (range 3 to 16, standard deviation 10.3). The SF36 showed
      an improvement in the pain scores for all patients (mean 22 points) and an
      overall improvement of 10 points for the sections on role limitation due to
      physical health. There was an overall decline in perceived general health (9
      points) and in role limitation due to emotional health (23 points). CONCLUSIONS:
      As all 10 patients showed improved scores on the OSDQ, in spite of the long
      standing nature of many of their shoulder problems, this rehabilitation programme
      was shown to improve shoulder function in this group of patients. The variation
      shown in the quality of life scores reflects the age group of this cohort who had
      a mean age of 75.5 years. All patients deemed their pain and function to have
      improved over the three-month period.

PMID- 17042026
TI  - Personal impact of disability in osteoarthritis: patient, professional and public
      values.
AB  - BACKGROUND: Osteoarthritis (OA) is a leading cause of disability. Numerous tools
      are available to assess this, but they fail to place a patient value upon
      disability. In rheumatoid arthritis, research has shown patients have different
      importance values for similar disabilities, and these individual values can be
      used to weight disability levels, creating a measure of personal impact.
      OBJECTIVES: Firstly, to determine if the Health Assessment Questionnaire (HAQ)
      can be used as the basis for an importance value scale by assessing if it
      includes activities considered important by OA patients. Secondly, to determine
      if the weights used for the value scale should be based on population, healthcare
      professional or patient values. METHOD: Twenty-five OA patients, 25 healthy
      controls and 25 healthcare professionals rated the importance of the items on the
      HAQ and shortened Modified HAQ (MHAQ). Prior to completing the HAQ, patients
      generated a list of activities that were important to them. RESULT: The HAQ
      contained 69% of items that patients considered important. No items were
      consistently deemed unimportant by patients. There was low agreement within and
      between groups about the importance of the items on the HAQ and MHAQ. CONCLUSION:
      The HAQ is a suitable basis for a value scale for an OA disability impact score.
      Importance values for function differed for patients, healthcare professionals
      and the general population; therefore individual patient weightings need to be
      used. Further work is under way to validate a measure of the personal impact of
      disability in patients with lower limb OA.

PMID- 17042027
TI  - Exploring the perceived role and impact of the nurse consultant.
AB  - BACKGROUND: Nurse consultant roles were introduced in 1999 with defined role
      criteria including expert practice, research, education and leadership. The
      primary objective of the role is to develop nurses and nursing to provide
      effective patient outcomes. In 2000 the first nurse consultant in rheumatology
      was appointed to establish a co-ordinated service for the management of patients
      with chronic musculoskeletal pain. There are now ten nurse consultants within
      rheumatology yet little is known of their role or impact. AIM: The aim of the
      study was to identify the perceived role and impact of one nurse consultant (NC)
      in rheumatology within the context of being a practitioner-researcher. METHOD:
      Seven peers of the NC and five patients cared for by the NC participated in a
      semi-structured interview to identify their perceptions regarding the role of the
      NC within the rheumatology service. RESULTS: The following themes were identified
      from the interviews: (1) development of a new model of care for patients with
      chronic musculoskeletal pain; (2) holistic person-centred care experienced and
      valued by the patient; (3) leadership and education; and (4) feeling cared for.
      CONCLUSION: The NC role had impacted on service development and culture in the
      instigation of a chronic musculoskeletal pain service and leadership and
      education activities. Patients experienced the holistic nature of the role.

PMID- 17042028
TI  - The new British Society for Rheumatology disease modifying anti-rheumatic drugs
      guidelines.

PMID- 17042029
TI  - Competency frameworks and the changing workforce.

PMID- 17042030
TI  - Bats as a continuing source of emerging infections in humans.
AB  - Amongst the 60 viral species reported to be associated with bats, 59 are RNA
      viruses, which are potentially important in the generation of emerging and re
      emerging infections in humans. The prime examples of these are the lyssaviruses
      and Henipavirus. The transmission of Nipah, Hendra and perhaps SARS coronavirus
      and Ebola virus to humans may involve intermediate amplification hosts such as
      pigs, horses, civets and primates, respectively. Understanding of the natural
      reservoir or introductory host, the amplifying host, the epidemic centre and at
      risk human populations are crucial in the control of emerging zoonosis. The
      association between the bat coronaviruses and certain lyssaviruses with
      particular bat species implies co-evolution between specific viruses and bat
      hosts. Cross-infection between the huge number of bat species may generate new
      viruses which are able to jump the trans-mammalian species barrier more
      efficiently. The currently known viruses that have been found in bats are
      reviewed and the risks of transmission to humans are highlighted. Certain
      families of bats including the Pteropodidae, Molossidae, Phyllostomidae, and
      Vespertilionidae are most frequently associated with known human pathogens. A
      systematic survey of bats is warranted to better understand the ecology of these
      viruses.

PMID- 17042031
TI  - Prenatal diagnosis of trisomy 21 without the Down syndrome phenotype.
AB  - OBJECTIVE: To report a patient with the prenatal diagnosis of trisomy 21 without
      the clinical Down syndrome (DS) phenotype secondary to the absence of the Down
      syndrome chromosomal region (DSCR) in a derivative chromosome 21. CASE REPORT AND
      METHODS: A newborn patient with prenatal diagnosis of duodenal atresia.
      Cytogenetic studies revealed a regular trisomy 21. At birth, she did not present
      the clinical features of DS. FISH analysis was performed in the patient with the
      LSI spectrum probe for the DSCR and in the mother with FISH multicolor analysis
      using painting probes for chromosomes 20 and 21. RESULTS: FISH analysis in the
      patient showed two hybridization signals suggesting that the third chromosome 21
      did not have the DSCR region explaining the absence of the DS phenotype. FISH
      multicolor analysis in the mother showed three hybridization signals for
      chromosomes 20 and 21, concluding a maternal karyotype,
      46,XX,t(20;21)(p11.2;q22.1). CONCLUSIONS: The patient was found to have a
      derivative chromosome 21 secondary to a nondisjunction error in meiosis II
      without the DS critical region and the phenotype was mostly secondary to the
      combination of the two partial trisomies.

PMID- 17042032
TI  - Structural elucidation of nitro-substituted five-membered aromatic heterocycles
      utilizing GIAO DFT calculations.
AB  - The GIAO (Gauge Including Atomic Orbitals) DFT (Density Functional Theory) method
      is applied at the B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d), B3LYP/6
      311++G(d,p)//B3LYP/6-31+G(d), B3LYP/6-311+G (2d,p)//B3LYP/6-31+G(d) and B3LYP/6
      311++G(d,p)//B3LYP/6-311++G(d,p) levels of theory for the calculation of proton
      and carbon chemicals shifts and coupling constants for 25 nitro-substituted five
      membered heterocycles. Difference (1D NOE) spectra in combination with long-range
      gHMBC experiments were used as tools for the structural elucidation of nitro
      substituted five-membered heterocycles. The assigned NMR data (chemical shifts
      and coupling constants) for all compounds were found to be in good agreement with
      theoretical calculations using the GIAO DFT method. The magnitudes of one-bond
      (1JCH) and long-range (nJCH, n>1) coupling constants were utilized for
      unambiguous differentiation between regioisomers of nitro-substituted five
      membered heterocycles.

PMID- 17042033
TI  - Gene duplications in 21-hydroxylase deficiency: the importance of accurate
      molecular diagnosis in carrier detection and prenatal diagnosis.
AB  - BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general
      population requires that misinterpretations of apparently severe mutations in
      alleles carrying duplicated genes be avoided. Prenatal treatment prevents
      virilization in female fetuses and genetic counseling may be offered to couples
      in which one partner is either a patient or a carrier. This paper proposes a
      semiquantitative PCR method involving primer extension that distinguishes the
      severe point mutation Q318X in single gene copy alleles from the
      normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA
      from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD
      carriers or patients, and one fetal sample (as well as the DNA of his family)
      were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific
      oligonucleotides hybridization for common mutations, Southern analysis,
      complementary direct sequencing and microsatellite typing. Primer extension
      analysis of the Q318X variants using fluorescent dideoxynucleotides was performed
      on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients,
      potential carriers and prenatal samples. RESULTS: Different fluorescence patterns
      were seen for the severe mutation (single gene copy) and the nondeficient (gene
      duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M)
      ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In
      all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M
      ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method
      discriminated between the severe Q318X mutation and the normal Q318X variant in
      gene duplication, and could be a useful complementary tool in prenatal diagnosis
      and carrier detection.

PMID- 17042034
TI  - The "Consecutive Combined Test"--using double test from week 8 + 0 and nuchal
      translucency scan, for first trimester screening for Down syndrome.
AB  - OBJECTIVE: To test the performance of the "Consecutive Combined Test", applied on
      a high-risk population. The classic "Combined Test" (Double test (DT) and Nuchal
      Translucency (NT) measurement on the same day at app. week 12) gives detection
      rates (DR) for Down syndrome (DS) of 80-90% for false positive rates (FPR) of 5%.
      In affected pregnancies, however, the low PAPP-A level is more pronounced, the
      earlier in pregnancy. Thus, we hypothesized that the Double Test could be taken
      as early as from week 8 + 0, without compromising the excellent performance of
      the Combined Test. This "Consecutive Combined Test" allows for a centralised
      laboratory function. METHODS: Inclusion criteria were maternal age > 35 years
      (80%) or a family history (20%). Double test was taken at a median gestational
      age (GA) = 10 weeks. NT was measured at GA = 11 + 0 - 13 + 6. A combined risk
      estimate of > 1:400 at birth was used as cut-off. RESULTS: 881 had the full test.
      Screen positive = 34. CVS with aneuploidy = 11 (6 trisomy-21, 5 others). FPR =
      3.2%. Positive Predictive Value (PPV) = 17.6% for T-21. CONCLUSION: The
      "Consecutive Combined Test" applied on a high-risk population seems to be highly
      efficient with a remarkably high PPV.

PMID- 17042036
TI  - Silica-immobilized chromium colloids for cyclohexane autoxidation.

PMID- 17042035
TI  - Cervical length in women in preterm labor with intact membranes: relationship to
      intra-amniotic inflammation/microbial invasion, cervical inflammation and preterm
      delivery.
AB  - OBJECTIVE: Intra-amniotic infection, diagnosed by microbial invasion of the
      amniotic cavity (MIAC) and/or the presence of intra-amniotic inflammation (IAI),
      is related to adverse perinatal outcome in women with preterm labor. Due to the
      subclinical nature of IAI, a correct diagnosis depends on amniocentesis, which is
      an invasive method not performed as a clinical routine. The aim of this study was
      to evaluate if cervical length measured by transvaginal sonography could assist
      in the identification of women at high risk for IAI. METHODS: Cervical length was
      assessed by transvaginal sonography in 87 women with singleton pregnancies in
      preterm labor (<34 weeks of gestation). Cervical (n=87) and amniotic (n=55)
      fluids were collected. Polymerase chain reactions for Ureaplasma urealyticum and
      Mycoplasma hominis, and culture for aerobic and anaerobic bacteria, were
      performed. Interleukin (IL)-6 and IL-8 were analyzed by enzyme-linked
      immunosorbent assay. RESULTS: IAI was present in 25/55 (45%) of the patients
      presenting with preterm labor who underwent amniocentesis. Women with IAI had a
      significantly shorter cervical length (median, 10 (range, 0-34) mm) than had
      those without IAI (median, 21 (range, 11-43) mm) (P<0.0001). Receiver-operating
      characteristics curve analysis showed that a cervical length (cut-off of 15 mm)
      predicted IAI (relative risk, 3.6; CI, 1.9-10.0) with a sensitivity of 72%,
      specificity of 83%, positive predictive value of 78% and negative predictive
      value of 78%. Cervical length was also significantly associated with preterm
      birth up to 7 days from sampling and at <or=34 weeks. CONCLUSION: Cervical length
      assessed by transvaginal sonography predicts IAI as well as preterm birth and
      could thereby be a useful clinical tool in the management of patients in preterm
      labor.

PMID- 17042037
TI  - A highly efficient and practical method for catalytic asymmetric vinylogous
      Mannich (AVM) reactions.

PMID- 17042038
TI  - Structure of a discrete dichloride hexahydrate cube as a
      tris(diisopropylamino)cyclopropenium salt.

PMID- 17042039
TI  - Theoretical analysis of the terahertz spectrum of the high explosive PETN.
AB  - The experimental solid-state terahertz (THz) spectrum (3 to 120 cm(-1)) of the
      high explosive pentaerythritol tetranitrate (PETN, C(5)H(6)N(4)O(12)) has been
      modeled using solid-state density functional theory (DFT) calculations. Solid
      state DFT, employing the BP density functional, is in best qualitative agreement
      with the features in the previously reported THz spectrum. The crystal
      environment of PETN includes numerous intermolecular hydrogen-bonding
      interactions that contribute to large (up to 80 cm(-1)) calculated shifts in
      molecular normal-mode positions in the solid state. Comparison of the isolated
      molecule and solid-state normal-mode calculations for a series of density
      functionals reveals the extent to which the inclusion of crystal-packing
      interactions and the relative motions between molecules are required for
      correctly reproducing the vibrational structure of solid-state THz spectra. The
      THz structure below 120 cm(-1) is a combination of both intermolecular (relative
      rotations and translations) and intramolecular (torsions, large amplitude
      motions) vibrational motions. Vibrational-mode analyses indicate that the first
      major feature (67.2 cm(-1)) in the PETN THz spectrum contains all of the optical
      rotational and translational cell modes and no internal (molecular) vibrational
      modes.

PMID- 17042040
TI  - Trapping norovirus by glycosylated hydrogels: a potential oral antiviral drug.

PMID- 17042041
TI  - Triphenylphosphane-functionalised amphiphilic copolymers: tailor-made support
      materials for the efficient and selective aqueous two-phase hydroformylation of 1
      octene.
AB  - Amphiphilic copolymers (random P1 and block P2) based on 2-oxazolines were
      synthesised with triphenylphosphane ligands covalently linked to the polymers by
      means of a metal-free synthesis route. The resulting macroligands were used in
      the aqueous two-phase hydroformylation of 1-octene. The influence of the polymer
      architecture (random and block copolymers) on activity and selectivity of the
      hydroformylation reaction was investigated and compared with that of
      nonfunctionalised copolymers (random P3 and block P4) and
      Rh(I)/triphenylphosphane trisulfonate as a water-soluble catalyst. The highest
      activities were observed for the random copolymer P1 (p=50 bar, T=100 degrees C,
      c=8 x 10(-4) mol L(-1)) with a turnover frequency (TOF) of 3700 h(-1), whereas
      the corresponding block copolymer P2 reached TOF numbers of 1630 h(-1).
      Additionally, both macroligands indicated efficient suppression of isomerisation
      and led to almost constant n/iso selectivities of about 3 after complete
      substrate conversion. Copolymers P3 and P4 showed, under identical reaction
      conditions, strong isomerisation after 40-60 % conversion (n/iso approximately
      0.7) and maximum activities of 1560 h(-1) (P3) and 1330 h(-1) (P4) at a
      concentration of 5 x 10(-3) mol L(-1).

PMID- 17042042
TI  - Silica gel triggered transformations of 3-methylenecyclopropylmethyl sulfonates
      to 3-methylenecyclobutyl analogues: experimental and computational studies.
AB  - Methylenecyclopropylcarbinols treated with sulfonyl chloride and Et(3)N form the
      sulfonated products in almost quantitative yields, which can be transformed to
      the corresponding 3-methylenecyclobutyl sulfonates with silica gel chromatography
      work-up. The rational explanation was proposed on the basis of computational
      studies.

PMID- 17042043
TI  - Donor/conductor/acceptor triads spatially organized on the micrometer-length
      scale: an alternative approach to photovoltaic cells.
AB  - We have used porous anodised Al(2)O(3) membranes as inert matrix for constructing
      and organizing spatially ternary donor/conductor/acceptor (DCA) systems
      exhibiting photovoltaic cell activity on the micrometric-length scale. These DCA
      triads were built stepwise by first growing a conducting polymer inside the
      membrane pores, thus forming nanorods that completely fill the internal pore
      space of the membrane. Then, an electron donor and an electron acceptor were
      adsorbed one on each side of the membrane, so that they were separated by a
      distance equal to the membrane thickness (ca. 60 microm), but electronically
      connected through the conductive polymer. When this device was placed between two
      electrodes and irradiated with visible light, electrons jumped from the donor
      molecule, crossed the membrane from side to side through the conductive polymer
      (a journey of about 60 microm!) until they finally reach the acceptor molecule.
      In so doing, an electric voltage was generated between the two electrodes,
      capable of maintaining an electric current flow from the membrane to an external
      circuit. Our DCA device constitutes the proof of a novel concept of photovoltaic
      cells, since it is based on the spatial organization at the micrometric scale of
      complementary, but not covalently linked, electron-donor and electron-acceptor
      organic species. Thus, our cell is based in translating photoinduced electron
      transfer between donors and acceptors, which is known to occur at the molecular
      nanometric scale, to the micrometric range in a spatially organised system. In
      addition our cell does not need the use of liquid electrolytes in order to
      operate, which is one of the main drawbacks in dye-sensitised solar cells.

PMID- 17042044
TI  - Protonated heme.
AB  - The ions formally corresponding to protonated heme [Fe(II)-hemeH](+) have been
      obtained by collision-induced dissociation from the electrospray ionization of
      microperoxidase (MP11) and their gas-phase chemistry has been studied by FTICR
      mass spectrometry. H/D-exchange reactions, used as a tool to gain information on
      the protonation sites in polyfunctional molecules, show that labile hydrogens
      pertain to the propionyl substituents at the periphery of the protoporphyrin IX.
      Several conceivable isomers for protonated heme have been evaluated by density
      functional theory. The most stable among the species investigated is the one
      corresponding to protonation at the beta carbon atom of a vinyl group, yielding a
      proton affinity (PA) value for [Fe(II)-heme] of 1220 kJ mol(-1). This high PA is
      consistent with the inertness of the hydrogen atoms at the protonation site
      towards H/D exchange with ND(3) and CD(3)CO(2)D. Peculiar features of this
      [Fe(II)-hemeH](+) isomer emerge by analysis of its electronic structure, showing
      that the vinyl group undergoing formal protonation has gained significant radical
      character due to electron transfer from the metal center. As a consequence, the
      iron atom acquires partial iron(III) character and none of the two formal
      descriptions [Fe(II)-hemeH(+)] and [Fe(III)-hemeH(.)](+) alone may adequately
      illustrate the protonated heme ion. In agreement with this description, the
      reactivity of protonated heme presents dual facets, resembling iron(III) in some
      aspects and iron(II) in others. On the one hand, protonated heme behaves like
      [Fe(III)-heme](+) ions in H/D-exchange reactions. On the other, it shows markedly
      decreased reactivity towards the addition of ligands with the notable exception
      of NO, in line with the high affinity shown by iron(II) complexes towards this
      molecule, NO, of key biological role.

PMID- 17042045
TI  - Redox-controlled interaction of biferrocenyl-terminated dendrimers with beta
      cyclodextrin molecular printboards.
AB  - This paper describes the synthesis and electrochemistry of biferrocenyl
      terminated dendrimers and their beta-cyclodextrin (beta-CD) inclusion complexes
      in aqueous solution and at surfaces. Three generations of poly(propylene imine)
      (PPI) dendrimers, decorated with 4, 8, and 16 biferrocenyl (BFc) units,
      respectively, were synthesized. A water-soluble BFc derivative forms stable
      inclusion complexes with beta-CD. The intrinsic binding constant is K(i)=2.5 x
      10(4) M(-1). The BFc dendrimers were solubilized in water by complexation of the
      end groups with beta-CD, resulting in large water-soluble supramolecular
      assemblies. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV)
      showed that all the end groups are complexed to beta-CD. Adsorption of the
      dendrimers at self-assembled monolayers (SAMs) of heptathioether-functionalized
      beta-CD on gold ("molecular printboards") resulted in stable monolayers of the
      dendrimers due to the formation of multivalent host-guest interactions between
      the BFc end groups of the dendrimers and the immobilized beta-CD molecules. The
      number of interacting end groups is 3, 4, and 4 for dendrimer generations 1, 2,
      and 3, respectively. The complexation of BFc to beta-CD is sensitive to the
      oxidation state of the BFc unit. Oxidation of neutral BFc-Fe(2) ((II,II)) to the
      cationic, mixed-valence biferrocenium BFc-Fe(2) ((II,III)+) resulted in
      dissociation of the host-guest complexes. Scan-rate-dependent CV and DPV analyses
      of the dendrimer-beta-CD assemblies immobilized at the beta-CD host surface and
      in solution revealed that the dendrimers are oxidized in three steps. First, the
      surface-beta-CD-bound BFc moieties are oxidized to the mixed-valence state, Fe(2)
      ((II,III)+), followed by the oxidation of the non-surface-interacting BFc groups
      to the Fe(2) ((II,III)+) state. The third step involves the oxidation of all the
      BFc moieties to the Fe(2) ((III,III)2+) state.

PMID- 17042046
TI  - Synthesis, structures, and properties of meso-phosphorylporphyrins: self
      organization through P-oxo-zinc coordination.
AB  - The synthesis, structures, and optical and electrochemical properties of meso
      phosphorylporphyrins are described. The copper-catalyzed carbon-phosphorus cross
      coupling reaction of a meso-iodoporphyrin with di-n-butyl phosphite and
      diphenylphosphane oxide has proved to be an efficient and general method for the
      synthesis of meso-phosphorylporphyrins. Zinc phosphorylporphyrins thus obtained
      readily undergo self-organization through P-oxo-Zn coordination to form
      noncovalently linked, cofacial porphyrin dimers or linear oligomers, which have
      been characterized by spectroscopic methods and X-ray crystallographic analyses.
      In toluene, CH(2)Cl(2), and CHCl(3), the zinc phosphorylporphyrins exist mostly
      as dimers or monomers, depending on their concentrations, the temperature, and
      the presence of additives. The self-association constants for dimerization in
      toluene have been determined by UV/Vis absorption titration measurements. The
      meso-diphenylphosphorylporphyrin dimer displays excitonic coupling of the Soret
      band with a splitting energy of 940 cm(-1). Fluorescence lifetimes of the zinc
      phosphorylporphyrins have been found to be affected only slightly by the
      concentration of the solution, and by the addition of triphenylphosphane oxide,
      suggesting that the effect of dimerization on their photodynamics in the S(1)
      state is negligible. On the other hand, the effect of dimerization is clearly
      reflected in their electrochemical oxidation processes, as the initially produced
      radical cations are efficiently delocalized over the two porphyrin rings. These
      findings demonstrate the potential utility of meso-phosphorylporphyrins as new
      models for the special pair in photosynthesis and as new building blocks for
      porphyrin-based supramolecular materials.

PMID- 17042047
TI  - Preparation and structure of mono- and binuclear half-sandwich iridium,
      ruthenium, and rhodium carbene complexes containing 1,2-dichalcogenolao 1,2
      dicarba-closo-dodecaboranes.
AB  - The synthesis of half-sandwich transition metal complexes containing both 1,2
      dichalcogenolato-1,2-dicarba-closo-docecaborane (Cab(E,E))
      [Cab(E,E)=E(2)C(2)(B(10)H(10)); E = S, Se] and N-heterocyclic carbene (NHC)
      ligands is described. Addition of mono-NHC ligand to the 16e half-sandwich
      dichalcogenolato carborane complexes [Cp*Rh(Cab(E,E))], [Cp*Ir(Cab(S,S))], [(p
      cymene)Ru(Cab(S,S))] (Cp* = pentamethylcyclopentadienyl) gives corresponding
      mononuclear 18e dithiolate complexes of the type [LM(Cab(E,E))(NHC)]:
      [Cp*M(Cab(S,S))(1-ethenyl-3-methylimidazolin-2-ylidene)] (M = Ir (2), Rh (3)),
      [Cp*Rh(Cab(E,E))(3-methyl-1-picolyimidazolin-2-ylidene)] [E = S (6), Se (7)], [(p
      cymene)Ru(Cab(S,S))(NHC)] [NHC = 1-ethenyl-3-methylimidazolin-2-ylidene (4), 3
      methyl-1-picolyimidazolin-2-ylidene (8)], whereas bis-NHC give centrosymmetric
      binuclear complexes [{Cp*M(Cab(S,S))}(2)(1,1'-dimethyl-3,3'-methylene(imidazolin
      2-ylidene))] [M = Rh (10), Ir (11)]. The complexes were characterized by IR, NMR
      spectroscopy and elemental analysis. In addition, X-ray structure analyses were
      performed on complexes 2-4, 6, 8, 10 and 11.

PMID- 17042048
TI  - Fluorescent sensors for Hg(2+) in micelles: a new approach that transforms an ON
      OFF into an OFF-ON response as a function of the lipophilicity of the receptor.
AB  - A new approach to the use of micelles in the fluorescent sensing of metal cations
      is proposed and applied to the case of Hg(2+). We demonstrate how it is possible
      to transform a system from an ON-OFF to an OFF-ON sensor by changing the length
      of the chain used to lipophilise a ligand that resides inside TritonX-100
      micelles together with pyrene as the fluorophore. Three tetrathia-monoaza
      macrocyclic ligands have been synthesised with the same ring but functionalised
      on the nitrogen atom with a methyl (C1-NS4), an n-butyl (C4-NS4) or an n-dodecyl
      (C12-NS4) chain. The three ligands have been fully characterised in water
      containing TritonX-100 micelles by means of potentiometric titrations and their
      apparent protonation and complexation constants with Hg(2+) were determined. On
      the basis of the distribution diagrams obtained, the more lipophilic C12-NS4 has
      been developed as an ON-OFF fluorescent sensor for mercury: working at pH<4, in
      the absence of Hg(2+) the ligand is inside the micelles, protonated and non
      quenching, while on addition of mercury the [C12-NS4Hg](2+) complex forms which
      remains inside the micelles and is quenching. On the other hand, the ligand of
      intermediate chain length, C4-NS4, can be used to obtain an OFF-ON sensor at
      7.0<pH<9.5. In the absence of added metal at pH>7.0 the ligand is unprotonated,
      it stays inside the micelles and is quenching, while addition of Hg(2+) in the
      7.0-9.5 pH range results in the formation of [C4-NS4Hg](2+), which is hydrophilic
      enough to leave the micelles and to be released into the bulk solution where it
      is no longer capable of quenching pyrene fluorescence. Additional studies on C1
      NS4, C3-NS4 and C8-NS4 indicate that the optimal chain length to observe this OFF
      ON behaviour is C(3)-C(4).

PMID- 17042049
TI  - P(8) (8-) polyanion with phosphorus atoms in three different formal oxidation
      states stabilized by a combination of Ag(+) and Hg(2+) cations.

PMID- 17042050
TI  - Surface modification of a six-capped body-centered cube Ni9W6 cluster: structure
      and single-molecule magnetism.

PMID- 17042051
TI  - Selective electrochemical retro-cycloaddition reaction of pyrrolidinofullerenes.

PMID- 17042052
TI  - A highly efficient palladium nanocatalyst anchored on a magnetically
      functionalized polymer-nanotube support.

PMID- 17042053
TI  - Reversible red fluorescent molecular switches.

PMID- 17042054
TI  - Ankylosing spondylitis: a dual perspective of current issues and challenges.
AB  - This series of articles on ankylosing spondylitis (AS) provides insight into the
      burden of disease and focuses on early diagnosis and effective management. AS
      leads to progressive functional impairment over time and has tremendous impact on
      society at large in terms of economic costs and indirect costs associated with
      physical impairment and loss of employment. Early diagnosis is crucial now that
      we have more effective therapy with tumor necrosis factor (TNF) antagonists,
      which suppress disease activity and improve the functional ability of patients
      whose disease is refractory to conventional drug therapy. Early identification of
      variables that help predict severe disease with bad functional prognosis is
      needed. If biological therapy with TNF inhibitors is proven to retard disease
      progression and prevent or delay functional limitations, insight into such
      prognosticators will help us offer the correct treatment to the correct patient
      at the correct time. There is also a need to demonstrate longterm benefits of
      such a therapy as well as a favorable cost/benefit ratio to help convince
      healthcare authorities, insurance companies, and others of the utility of these
      drugs for treating patients with AS refractory to conventional drug therapy.

PMID- 17042055
TI  - The burden of ankylosing spondylitis.
AB  - The acute as well as chronic clinical features of ankylosing spondylitis (AS) are
      a burden to the patient and society. Apart from the axial and articular
      manifestations, extraarticular AS-related comorbidities such as uveitis,
      inflammatory bowel disease, and psoriasis contribute to the burden of the
      disease. In addition, a large proportion of patients have osteoporosis or
      osteopenia, which may be associated with fractures and contribute to kyphosis.
      All these features result in decreased quality of life. Moreover, patients with
      AS have an increased mortality rate. The impact of this disease also can be seen
      in various aspects of workforce participation, from requiring more assistance at
      paid work to withdrawal from the workforce. Further, patients with AS and,
      subsequently, society are affected by substantial healthcare costs related to
      medications and healthcare provider expenses. Early diagnosis and management of
      patients will likely prevent functional disability and improve patient outcomes.

PMID- 17042056
TI  - Diagnosing ankylosing spondylitis.
AB  - This article focuses on the early diagnosis and effective management of
      ankylosing spondylitis (AS), a disease that is not uncommon and that can cause
      early retirement and severe functional disability. AS, like most other
      rheumatologic diseases, has no diagnostic gold standard. Correct diagnosis
      depends largely on a constellation of clinical symptoms and signs in addition to
      radiological findings. Early diagnosis has become all the more important because
      effective therapies are available: tumor necrosis factor antagonists that
      suppress disease activity and improve functional ability in patients with AS
      refractory to conventional drug therapy. The biologic agents are probably even
      more effective if given early. Inflammation of the sacroiliac joints and the
      spine is a common, early feature and possibly the most frequent first
      manifestation of disease. Therefore, its early detection is important, and
      magnetic resonance imaging has proven useful in this regard. To optimize
      diagnostic accuracy of early disease, it is crucial to use a comprehensive
      approach and have a deep understanding of the disease and its clinical picture.
      The clinician should gather a complete history, paying close attention to all the
      elements of this multisystem disease, as well as judiciously ordering laboratory
      testing and imaging. New strategies are being developed to assist primary care
      physicians in their screening for these patients, which in turn should result in
      early referral to rheumatologists and early diagnosis.

PMID- 17042057
TI  - Treatment of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a condition characterized by inflammatory back
      pain and associated with considerable disability and diminished quality of life
      in affected individuals. The condition is undertreated in part due to a delay in
      diagnosis and limited therapeutic interventions. Although traditional treatment
      approaches (physical therapy, exercise, patient education, nonsteroidal
      antiinflammatory drugs) remain important components of the management of AS, the
      demonstrated efficacy of tumor necrosis factor-a (TNF-a) antagonists such as
      etanercept and infliximab have allowed clinicians to more effectively manage this
      condition. These targeted therapies have demonstrated rapid and consistent
      effectiveness in reducing the axial and peripheral symptoms of AS, slowing
      disease progression, and improving patient function and quality of life.
      Appropriate and timely use of TNF-a antagonists offers additional options for
      patients with active AS who are inadequately controlled with conventional
      treatment.

PMID- 17042058
TI  - From health to peace in Afghanistan--the story so far.

PMID- 17042059
TI  - Socioeconomic stress and drug consumption: unemployment as an adverse health
      factor in Croatia.
AB  - AIM: To explore to what degree unemployment was related to health problems
      expressed in terms of consumption of prescription drugs in Croatian citizens.
      METHODS: Based on the Croatian Institute for Health Insurance data for 2003, the
      number of prescriptions per insured individual (NPI) was calculated for employed
      and unemployed persons, as well as for different subsets according to the region
      (Zagreb, Split, Rijeka, Osijek), age, gender, and prescribed drug category.
      RESULTS: During 2003, a total of 1 003 547 drugs were prescribed to 949 746
      health-insured persons aged 18-69 years. NPI was 32% higher for unemployed than
      for employed citizens; it averaged 0.995 among the employed, and 1.317 among the
      unemployed. Differences in NPI (DeltaNPI) between the employed and the unemployed
      varied within the subsets; the largest difference was observed in the Zagreb
      region (DeltaNPI =0.522), in the 30-39 age group (DeltaNPI =0.563), in men
      (DeltaNPI =0.565), and for anxiolytic/antidepressant drugs (DeltaNPI =0.184).
      CONCLUSION: Our findings indicate that unemployed Croatian citizens used more
      drugs, which calls for the implementation of health care measures to reduce or
      prevent their medical problems, particularly those affecting mental health.
      Medical problems associated with unemployment present a specific burden for
      family medicine and the health care system.

PMID- 17042060
TI  - Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally
      advanced resectable rectal cancer: prospective phase II trial.
AB  - AIM: To evaluate the efficacy and toxicity of preoperative chemoradiotherapy with
      capecitabine in locally advanced rectal cancer. METHODS: Between June 2004 and
      January 2005, 57 patients with operable, clinical stage II-III adenocarcinoma of
      the rectum entered the prospective phase II study. Radiation dose was 45 Gy
      (25x1.8 Gy). Concurrent chemotherapy with a daily dose of 1650 mg/m2 capecitabine
      was administered orally, divided into two equal doses per day, including
      weekends. Patients were evaluated weekly for acute toxicity and compliance with
      the protocol. Surgery was scheduled 6 weeks after the completion of the
      chemoradiotherapy. RESULTS: A single female patient died after receiving 27 Gy,
      because of pulmonary embolism. All other patients completed the preoperative
      chemoradiotherapy according to the protocol and a definitive operation was
      performed in all but one of these patients. The complete pathological response
      was recorded in 5 patients (9.1%). Tumor (T), lymph nodes (N), and overall
      downstaging rates were 40%, 52.9%, and 49.1%, respectively. Total sphincter
      preservation rate was 65.5% (36 out of 55 patients) and the rate in 27 patients
      with tumors located within 5 cm of the anal opening was 37% (10 out of 27
      patients). The most frequent side-effect of the combined therapy was dermatitis
      (grade 3 in 19 patients). After surgery, a single patient died due to sepsis
      during the early perioperative period. Nonlethal perioperative complications were
      recorded in 24/55 patients. CONCLUSION: Preoperative chemoradiotherapy with oral
      capecitabine is safe and well tolerated. It has a downstaging potential and can
      increase the possibility for sphincter preservation surgery.

PMID- 17042061
TI  - Antenatal assessment of discordant umbilical arteries in singleton pregnancies.
AB  - AIM: To assess the relationship between discordant umbilical arterial size and
      resultant blood flow parameters and determine the impact of discordance on fetal
      outcome. METHODS: This is a descriptive, cross-sectional study of 200 patients
      with a singleton gestation, who underwent a fetal anatomy survey between 18 to 23
      weeks of gestation, with documented umbilical cord morphological patterns and
      blood flow characteristics. Umbilical vessel diameters and Doppler parameters
      (umbilical vein blood flow volume, mean resistance index, and peak-systolic
      velocity) were analyzed for discordance. Discordances encountered were examined
      for their possible association with perinatal outcome. RESULTS: We had adequate
      ultrasound umbilical cord images, Doppler flow parameters, and all necessary
      demographic data for 154 patients. Umbilical artery discordance averaged 13.1%
      and was significantly correlated with both the expected and the true percent of
      difference in resistance index values (RI, P<0.001). In 12 patients (7.8%), a
      significant discordance of more than 29.5%, or 95th percentile, was observed
      between the two umbilical artery diameters. However, in these cases no associated
      adverse perinatal outcome or significant placental pathology was noted. There was
      no significant difference between patients discordant or concordant umbilical
      artery in terms of maternal, labor, and neonatal data. CONCLUSION: The magnitude
      of umbilical arteries' luminal discordance directly influences the corresponding
      blood flow parameters. In our sample of patients, the presence of discordant-in
      size umbilical arteries was not associated with umbilical cord or placental
      abnormalities.

PMID- 17042062
TI  - Effects of age on plasma glucose levels in non-diabetic Hong Kong Chinese.
AB  - AIM: To analyze the relationship between age and plasma glucose levels in Hong
      Kong Chinese population. METHODS: We performed a cross-sectional study with
      15,603 non-diabetic subjects from the community of Hong Kong. Plasma glucose
      concentration was measured in blood specimens from the subjects. The time of
      blood taking varied, depending on the availability of the patients. RESULTS:
      There were 11,148 (71.4%) women and 4455 (28.6%) men (mean age: 50.1+/-16.1
      years). There were 6901 (44.2%) patients who had plasma glucose measured in the
      fasting condition, 2999 (19.2%) who were 2-hour post-prandial, and 5703 (36.6%)
      who had plasma glucose measured at a random time. The correlation coefficients
      between age and plasma glucose levels in fasting, 2-hour post-prandial, and
      random group of patients were 0.159, 0.169, and 0.114, respectively (adjusted for
      body mass index, smoking, and gender; all P values <0.001). Fasting and random
      plasma glucose level increased by 0.15 mmol/L, while 2-hour post-prandial plasma
      glucose level increased by 0.26 mmol/L per decade-increase in age. CONCLUSION:
      Plasma glucose levels progressively increase with age in Hong Kong Chinese non
      diabetic subjects.

PMID- 17042063
TI  - Perinatal and maternal outcomes in Tuzla Canton during 1992-1995 war in Bosnia
      and Herzegovina.
AB  - AIM: To compare perinatal and maternal outcomes in Tuzla Canton during the 1992
      1995 war in Bosnia and Herzegovina with those before (1988-1991) and after (2000
      2003) the war. METHODS: We retrospectively collected data on a total of 59,707
      liveborn infants and their mothers from the databases of Tuzla University
      Department for Gynecology and Obstetrics and Tuzla Institute for Public Health.
      Data on the number of live births, stillbirths, early neonatal deaths, causes of
      death, gestational age, and birth weights were collected. We also collected data
      on the number of medically unattended deliveries, examinations during pregnancy,
      preterm deliveries, and causes of maternal deaths. Perinatal and maternal
      outcomes were determined for each study period. RESULTS: There were 23,194 live
      births in the prewar, 18,302 in the war, and 18,211 in the postwar period. Prewar
      perinatal mortality of 23.3 per 1000 live births increased to 25.8 per 1000 live
      births during the war (P<0.001), due to a significant increase in early neonatal
      mortality (10.3 per thousand before vs 15.1 per thousand after the war, P<0.001).
      After the war, both perinatal mortality (14.4 per thousand) and early neonatal
      mortality (6.6 per thousand) decreased (P<0.001 for both). The most frequent
      cause of early neonatal death during the war was prematurity (55.7%), with
      newborns most often dying within the first 24 hours after birth. During the war,
      there were more newborns with low birth weight (<2500 g), while term newborns had
      lower average body weight. Women underwent 2.4 examinations during pregnancy (5.4
      before and 6.3 after the war, P<0.001 for both) and 75.9% had delivery attended
      by a health care professional (99.1% before and 99.8% after the war; P<0.001 for
      both). Maternal mortality rate of 65 per 100,000 deliveries during the war was
      significantly higher than that before (39 per 100,000 deliveries) and after (12
      per 100,000 deliveries) the war (P<0.001 for both). CONCLUSION: Perinatal and
      maternal mortality in Tuzla Canton were significantly higher during the war,
      mainly due to lower adequacy and accessibility of perinatal and maternal health
      care.

PMID- 17042064
TI  - Prevalence of and risk factors for self-reported sexually transmitted infections
      in Slovenia in 2000.
AB  - AIM: To estimate the prevalence of self-reported sexually transmitted infections
      (STIs) and examine the associations between self-reported STIs and
      sociodemographic and behavioral factors among sexually active Slovenians aged 18
      49 years. METHODS: Data were collected during 1999-2001 from a probability sample
      of the general population at respondents' homes by a combination of face-to-face
      interviews and anonymous self-administered questionnaires. Statistical methods
      for complex survey data were used to account for stratification, clustered
      sampling, and weighing. RESULTS: The proportion of sexually active Slovenian
      population that reported ever being diagnosed with an STI, excluding pelvic
      inflammatory disease and vaginal discharge for women, was 5.5% for men and 5.1%
      for women. Gonorrhea was the most commonly self-reported STI among men (3.7%) and
      hepatitis B among women (1.7%). Independent risk factors associated with self
      reported STIs included having concurrent heterosexual relationships during
      lifetime [adjusted odds ratio (AOR) for men 3.3 (CI 1.3-8.6) and for women 2.3
      (CI 1.0-5.3)], ever having paid for sex for men (AOR 4.0, CI 1.5-10.7), and
      having at least 10 lifetime heterosexual partners for women (AOR 4.7, CI 1.7
      13.0). CONCLUSION: Our estimates of lifetime prevalence of self-reported STIs in
      a probability sample of Slovenian men and women aged 18 to 49 indicate a
      substantial national burden of STIs. The results could be used in shaping
      national STI prevention and control policies and strategies. Identification of
      risk factors associated with self-reported STIs provide a basis for targeting
      prevention and control efforts to individuals at higher risk.

PMID- 17042065
TI  - Consequences of domestic violence on women's mental health in Bosnia and
      Herzegovina.
AB  - AIM: To assess psychological consequences of domestic violence, and determine the
      frequency and forms of domestic violence against women in Bosnia and Herzegovina.
      METHODS: The study was carried out in the Tuzla Canton region in the period from
      2000 to 2002, and included 283 women aged 43+/-9.6 years. Out of 283 women, 104
      received psychiatric treatment at the Department for Psychiatry of the University
      Clinical Center Tuzla, 50 women were refugees; and 129 were domicile inhabitants
      of the Tuzla Canton. Domestic Violence Inventory, Cornell Index, Symptom
      Checklist-90-Revised, PTSD Checklist Version for Civilians, and Beck Depression
      Inventory were used for data collection. Basic sociodemographic data and
      information from the medical documentation of the Department for Psychiatry of
      the University Clinical Center Tuzla was also collected. RESULTS: Out of 283
      women, 215 (75.9%) were physically, psychologically, and sexually abused by their
      husbands. Among the abused, 107 (50.7%) experienced a combination of various
      forms of domestic violence. The frequency of domestic violence was high among
      psychiatric patients (78.3%). Victims of domestic violence had a significantly
      higher rate of general neuroticism, depression, somatization, sensitivity,
      obsessive-compulsive symptoms, anxiety, and paranoid tendency than women who were
      not abused. The prevalence of posttraumatic stress disorder (PTSD) symptoms
      according to the type of trauma was higher in women with the history of childhood
      abuse (8/11) and domestic violence (53/67) than in women who experienced war
      trauma (26/57) and the loss of loved ones (24/83). The majority of 104
      psychiatric patients suffered from PTSD in comorbidity with depression (n=45),
      followed by depression (n=17), dissociative disorder (n=13), psychotic disorder
      (n=7), and borderline personality disorder with depression (n=7). The intensity
      of psychological symptoms, depression, and Global Severity Index for
      Psychological Symptoms (GSI) were in significant positive correlation with the
      frequency of psychological (r=0.45, P<0.001), physical (r=0.43, P<0.001), and
      sexual abuse (r=0.37, P<0.001). CONCLUSION: Domestic violence in various forms
      had long-term consequences on mental health of women. This should be taken into
      account when treating women with war-related trauma.

PMID- 17042066
TI  - Domestic violence against women in Sivas, Turkey: survey study.
AB  - AIM: To determine the self-reported prevalence of domestic violence and
      associated risk factors in the Sivas province of Turkey. METHOD: Five hundred and
      eighty-three households were chosen by the method of stratified random sampling.
      The average age among women was 28.65+/-4.64. A total of 45.3% of women were in
      30-34 age-group, 76.5% were housewives, and 91.2% were married. The data were
      gathered by performing face-to-face interviews in participants' homes.
      Demographic data were obtained by fill-in forms. RESULTS: We found a
      statistically significant relationship among the types of violence and annual
      income, type of family, education and occupation level of women, education level
      of perpetrators, watching violent films, and childhood experience of emotional
      abuse or negligence. Fifty-two percent of women were exposed to at least one type
      of violence. Verbal violence was the most frequent type of violence (53.8%),
      followed by physical violence (38.3%). About 45% of women exposed to violence
      were in the 30-34 age group, 41.6% completed only primary schools, 73.6% were
      housewives, 91.7% were married, 71.0% had been exposed to violence during their
      childhood, and 45.2%, had been exposed to violence several times in a month.
      Economic problems were reported as the most important reason for domestic
      violence (31.4%). CONCLUSION: Our study found higher prevalence of domestic
      violence than expected. As an important public health problem, domestic violence
      requires a multidisciplinary approach to understand its causes and plan
      preventive measures.

PMID- 17042067
TI  - Mobbing, stress, and work ability index among physicians in Bosnia and
      Herzegovina: survey study.
AB  - AIM: To assess the frequency of reported mobbing and the association among
      mobbing, working environment factors, stress, health outcome, personality type,
      and work ability index in a sample of physicians in Bosnia and Herzegovina.
      METHOD: We conducted a questionnaire survey using a validated self-reported
      questionnaire among 511 physicians in national health sector of Bosnia and
      Herzegovina. The questions covered five major categories of mobbing behavior.
      Characteristics of the work, perceived work environment and its effects, stress,
      health, and satisfaction with work and life were assessed by the standardized
      abridged form of Occupational Stress Questionnaire (OSQ). A standardized
      questionnaire Work Ability Index (WAI) was used to determine the relation between
      mobbing and work ability. RESULTS: Of 511 surveyed physicians, 387 (76%)
      physicians self-reported mobbing behavior in the working environment and 136
      (26%) was exposed to persistent mobbing. More than a half of the physicians
      experienced threats to their professional status and almost a half felt isolated.
      Logistic regression analysis showed that lack of motivation, loss of self-esteem,
      loss of confidence, fatigue, and depressiveness were significantly associated
      with lack of support from colleagues. Intention to leave work was associated with
      lack of support from colleagues (OR 2.3, 95% CI, 1.065-3.535; t =4.296, P =0.003)
      and lack of support from superiors (OR 1.526, 95% CI, 0.976-2.076; t =5.753; P
      =0.001). Isolation or exclusion and threats to professional status were
      predictors for mental health symptoms. Persistent mobbing experience was a
      significant predictor for sick leave. CONCLUSION: Exposure to persistent threat
      to professional status and isolation or exclusion as forms of mobbing are
      associated with mental health disturbances and lack of self-esteem and
      confidence. Setting up a system of support for physicians exposed to mobbing may
      have important benefits.

PMID- 17042068
TI  - Between stigma and dawn of medicine: the last leprosarium in Croatia.
AB  - In an attempt to reconstruct the function of the last leprosarium in Croatia,
      situated in the little town of Metkovic in the Neretva valley, we used local folk
      tales and compared them with different data sources, such as register of deaths
      in the Roman Catholic parishes in Metkovic and the nearby village of Vidonje,
      archived local newspapers, building documents, and different artifacts from the
      beginning of the 20th century. We identified individuals and families who were
      treated in the leprosarium during its existence from 1905, when it was built,
      until 1925, when it was closed down. We analyzed why the Neretva river valley was
      chosen for the isolation of lepers. It seems that the geographical position of
      the region, close to the endemic seat of the disease in the neighboring Bosnia,
      was more important for the decision to build the leprosarium than the incidence
      of leprosy or some recent outbreak of the disease in Croatia. Building of
      leprosariums, such as this one in Metkovic, was a part of tradition of separating
      lepers from human community. This was considered as a socially and medically
      justified behavior in a time when it was not possible to identify the cause of
      leprosy and apply the proper treatment.

PMID- 17042069
TI  - Introductory course on getting to know journals and on "browsing" a research
      paper: first steps to proficiency in scientific communication.
AB  - AIM: To evaluate the effectiveness and appropriateness of a course that promotes
      familiarity with biomedical periodicals and teaches efficient reading skills.
      METHODS: A 16-hour course was designed to help inexperienced readers gain
      confidence navigating the contents of a research paper (instead of reading only
      abstracts), and make the first steps to critical appraisal. The course consisted
      of short lessons and small group work in which research papers were read and
      presented to the class. Participants learned a method called "browsing" that
      guides the first, superficial reading of a research paper and substitutes
      abstract reading. The course was administered to 15 hospital physicians and 40
      graduate students of molecular medicine, in 4 separate sessions. RESULTS: At
      course entry, 45 of 55 participants normally read the abstract before consulting
      the body of a research paper. An end-of-course questionnaire, completed by 47
      participants, revealed that only 3 would still read the abstract first, while 33
      would perform browsing, 7 would scan figures and tables, and 4 would consult
      another section of a paper outside of their research interests; similar responses
      were given for a research paper within their fields. For 43 participants, the
      course was effective in developing reading skills. On a final comprehension test,
      participants had a median score of 69% correct responses (interquartile range,
      56%-80%). CONCLUSION: This introductory course on reading scientific articles is
      effective in overcoming abstract-only reading and in developing confidence with
      the research literature. Considering participants' subjective evaluation and test
      scores, the course contents are appropriate for both physicians and young
      researchers.

PMID- 17042071
TI  - 34.8 degrees C and rising.

PMID- 17042070
TI  - Scientific production of research fellows at the Zagreb University School of
      Medicine, Croatia.
AB  - AIM: To evaluate scientific production among research fellows employed at the
      Zagreb University School of Medicine and identify factors associated with their
      scientific output. METHOD: We conducted a survey among research fellows and their
      mentors during June 2005. The main outcome measure was publication success,
      defined for each fellow as publishing at least 0.5 articles per employment year
      in journals indexed in the Current Contents bibliographic database. Bivariate
      methods and binary logistic regression were used in data analysis. RESULTS: A
      total of 117 fellows (response rate 95%) and 83 mentors (100%) were surveyed. The
      highest scientific production was recorded among research fellows employed in
      public health departments (median 3.0 articles, interquartile range 4.0),
      compared with those from pre-clinical (median 0.0, interquartile range 2.0) and
      clinical departments (median 1.0, interquartile range 2.0) (Kruskal-Wallis, P
      =0.003). A total of 36 (29%) research fellows published at least 0.5 articles per
      employment year and were considered successful. Three variables were associated
      with fellows' publication success: mentor's scientific production (odds ratio
      [OR], 3.14; 95% confidence interval [CI], 1.31-7.53), positive mentor's
      assessment (OR, 3.15; 95% CI, 1.10-9.05), and fellows' undergraduate publication
      in journals indexed in the Current Contents bibliographic database (OR, 4.05; 95%
      CI, 1.07-15.34). CONCLUSION: Undergraduate publication could be used as one of
      the main criteria in selecting research fellows. One of the crucial factors in a
      fellow's scientific production and career advancement is mentor's input, which is
      why research fellows would benefit most from working with scientifically
      productive mentors.

PMID- 17042072
TI  - Specialist training programs for African physicians.

PMID- 17042080
TI  - Outbreak news. Avian influenza, Egypt--update.

PMID- 17042081
TI  - Addressing the threat of tuberculosis caused by extensively drug-resistant
      Mycobacterium tuberculosis.

PMID- 17042082
TI  - The underrecognized burden of influenza.

PMID- 17042083
TI  - The underrecognized burden of influenza.

PMID- 17042084
TI  - Hospital volume and outcomes of mechanical ventilation.

PMID- 17042085
TI  - Intensive care of patients with HIV infection.

PMID- 17042086
TI  - [Very good effect of Hib vaccination in Kenya].

PMID- 17042087
TI  - Tooth sensitivity and whitening.
AB  - This article presents a review of the basic concepts of tooth sensitivity and how
      those concepts apply to cervical dentin hypersensitivity and the sensitivity
      frequently associated with tooth whitening. The etiology and treatment of
      cervical dentin hypersensitivity are described. The clinical presentation,
      incidence, and predisposing factors for sensitivity associated with tooth
      whitening also are discussed.

PMID- 17042088
TI  - Balanced force and rotary shaping.
AB  - Studies on instrument performance in clear acrylic canals have Professor Emeritus
      of Endodontics indicated that the helical angle of the cutting edge is a
      contributing factor Oklahoma City Oklahoma in instrument overload and failure. In
      clinical trials, changing the design of modern shaping instruments to eliminate
      the inclined angulations of the Private Practice in Endodontics cutting edges has
      proven to be beneficial by reducing the risk of fracture. Norman, Oklahoma Yet
      another benefit of a nonhelical cutting edge is that the flute space is
      accessible past the segment so that the fragment can be bypassed rather easily
      and the apex can be shaped with hand instruments. It appears that this feature
      may reduce the impact of a separated instrument.

PMID- 17042089
TI  - Endodontic and esthetic/restorative treatment of the same tooth: a synergistic
      approach for successful outcomes.
AB  - Endodontic and restorative treatment of compromised teeth should not be
      considered separate, unrelated procedures. It is beneficial for both the
      endodontist and the restorative dentist to consider the other's treatment of a
      patient with compromised teeth. Both practitioners should thoroughly understand
      their respective modalities and the ways in which their work affects the
      remaining structure and integrity of the teeth being treated. The restorative
      dentist also should be aware that there are 2 primary goals of endodontic
      treatment: cleaning and disinfecting the affected canals, and sealing those
      canals to prevent reinfection. The endodontist should be aware that the
      objectives of the restorative dentist are to ensure postoperative root strength,
      prevent vertical root fracture, and retain the core of the restoration. This
      article describes a synergistic approach to treating teeth requiring both
      endodontic and restorative treatment.

PMID- 17042090
TI  - Recent article on Thomas Evans.

PMID- 17042091
TI  - The management of abuse: 2. Child abuse.
AB  - The role of the GDP and the dental team in the recognition and management of
      child abuse is discussed. Information on the current legislation and protocols
      for referral are provided. CLINICAL RELEVANCE: This paper discusses child abuse
      and offers information and practical advice for the dental team.

PMID- 17042092
TI  - [Effect of potassium level on output and diosgenin content of Dioscorea
      zingiberensisg].
AB  - OBJECTIVE: To study the effect of potassium level on physiological
      characteristics and diosgenin content of Dioscorea zingiberensisg and provide
      experimental basis for proper use of potassium fertilizer. METHODS: Field
      experiment including four potassium levels was carried out. The physiological
      characteristics of leaves were determined at different growth stages and the
      diosgenin content in bulk root was assayed after harvest. RESULTS: Within the
      arrange of 0-180 kg K2SO4/hm2, the content of chlorophyll and amino acid, Fv/Fo,
      Fv/Fm, and phiPs II were increased with the increase in potassium level.
      Meanwhile, the ability to defense the damage caused by active oxygen was
      obviously enhanced. Further increase in potassium level resulted in the decrease
      in efficiency of potassium fertilizer. CONCLUSION: It indicats that higher yield
      and diosgenin content can be obtained when the potassium level is 180 kg K2/hm2.

PMID- 17042093
TI  - High-dose, single-bolus eptifibatide: a safe and cost-effective alternative to
      conventional glycoprotein IIb/IIIa inhibitor use for elective coronary
      interventions.
AB  - BACKGROUND: Adjunctive pharmacotherapy with eptifibatide, a glycoprotein (GP)
      IIb/IIIa inhibitor, as an intravenous bolus followed by infusion has been shown
      to improve outcomes in elective coronary interventions (PCI). However, bleeding
      complications and costs have limited the routine adoption of this regimen.
      PURPOSE: The goal of this study was to examine the safety, efficacy and cost
      effectiveness of high-dose, single-bolus eptifibatide, without post-intervention
      infusion, in "real-world" patients undergoing elective PCI. METHODS: We studied
      401 patients with stable and unstable angina who were treated with a high-dose
      (20 mg), single bolus of eptifibatide plus heparin prior to the start of elective
      PCI. Exclusion criteria included recent MI, stenting of bypass graft(s),
      rotational atherectomy and/or brachytherapy. The primary study endpoints were
      major adverse clinical events (MACE), defined as the in-hospital and 30-day
      incidence of death from any cause, Q-wave or non-Q-wave MI, repeat target vessel
      revascularization and/or major bleeding complications. RESULTS: Relevant
      demographic and procedural characteristics included mean age: 66.4 +/- 11.2; male
      gender: 242/401 (61%); number of vessels treated per patient: 1.46 +/- 0.42; and
      number of stents deployed per patient: 1.82 +/- 0.65. In-hospital non-Q-wave MI
      (CPK and/or CPK-MB > 3 times the upper limit of normal) occurred in 7/401
      patients (1.75%) and MACE was 2.25%. Major bleeding complications were seen in
      2/401 patients (0.49%). There were 4 additional MACE events at 30-day follow up
      (total MACE and bleeding = 3.25%). The average anticoagulation cost was 66
      dollars/patient. CONCLUSIONS: Intravenous eptifibatide, administered as a high
      dose (20 mg) single-vial bolus, is a safe, effective and highly cost-effective
      alternative to the conventional regimens of bolus plus prolonged intravenous GP
      IIb/IIIa inhibitor infusion for patients undergoing elective PCI.

PMID- 17042094
TI  - Five-year clinical follow up after intracoronary radiation for the prevention of
      in-stent restenosis.
AB  - Intracoronary radiation therapy (IRT), utilizing both gamma- and beta-emitting
      radiation sources, is considered to be a safe and effective treatment for in
      stent restenosis (ISR). Although no longer in clinical use, a significant number
      of patients were treated in the past with IRT, and their long-term outcomes have
      not been well documented. The aim of the present analysis was to document the
      long-term outcomes of all patients who underwent IRT at our institution for the
      prevention of recurrence of ISR. Data were collected from 132 patients (148
      irradiated lesions) treated with IRT at our institution between March 1999 and
      January 2004. Clinical and angiographic data were collected over a 5-year period.
      Patients were divided into 2 groups: those with failed IRT (n = 65), defined as a
      procedure that resulted in a major adverse cardiac event: death, myocardial
      infarction, target lesion revascularization, target vessel revascularization or
      coronary artery bypass graft surgery at any time during the follow-up period, and
      patients with successful IRT (n = 67). Both groups were identical regarding
      baseline clinical and angiographic characteristics, with the exception of a
      higher percentage of multivessel disease and diffuse restenosis in patients who
      failed IRT (p = 0.01). At 1-year follow up, slightly less than half (43%) of
      those patients in the failure group experienced a major adverse cardiac event.
      During the long-term follow up period, half of all patients who underwent IRT at
      our institution experienced a major adverse cardiac event, 61 patients (46%)
      either died or underwent a revascularization procedure, 16 patients (24%) had a
      myocardial infarction or died, and 55 patients (42%) required repeat coronary
      revascularization. The average time to develop a major adverse cardiac event was
      14.6 +/- 15 months. Therefore, during long-term follow up following IRT for the
      prevention of ISR, half of all patients developed a major cardiovascular event,
      mainly due to the need for repeat revascularization procedures.

PMID- 17042095
TI  - Commentary: Alternative safe, effective and cost-efficient dosing for
      eptifibatide in low-risk patients.

PMID- 17042096
TI  - Commentary: Can distal embolic protection yield better results in acute
      myocardial infarction treatment?

PMID- 17042097
TI  - Commentary: Bifurcations: the problem is the side branch.

PMID- 17042098
TI  - Distal protection during primary angioplasty: a feasibility and safety study
      utilizing a novel filter technology.
AB  - BACKGROUND: The degree of myocardial reperfusion after primary percutaneous
      coronary intervention (PCI) may be reduced by distal embolization. We tested the
      safety, feasibility and efficacy of a novel filter device, the Spider Distal
      Embolic Protection System, as an adjunct to primary PCI. METHODS AND RESULTS:
      Twenty consecutive patients undergoing primary PCI with the Spider Embolic
      Protection Device were included in the analysis. Successful Spider device
      positioning was obtained in all cases, with predilatation of the lesions in 1 of
      these cases (5%). There were no procedural complications attributable to the use
      of a filter. Histological analysis of the content of 5 filters showed multiple
      embolic debris in all cases, from 8 to 48 particles per filter, from 101-1,299 mm
      in diameter and from 212-1,487 mm2 in area. The use of the Spider filter was
      associated with a profound ST-segment resolution (STR: 85.6 +/- 16.5%) and the
      occurrence of complete (50%) STR of 90%. CONCLUSIONS: The Spider Embolic
      Protection Device as an adjunctive therapy during primary PCI is feasible and
      safe, preventing distal embolization and improving myocardial reperfusion.
      Currently, an international, multicenter, randomized clinical trial is
      prospectively testing this challenging hypothesis.

PMID- 17042099
TI  - Medicaid program; state allotments for payment of Medicare Part B premiums for
      qualifying individuals: federal fiscal year 2006 and fiscal year 2007. Final
      rule.
AB  - This final rule sets forth the methodology and process used to compute and issue
      each State's allotments for fiscal years (FY) 2006 and FY 2007 that are available
      to pay Medicare Part B premiums for qualifying individuals. It also provides the
      final FY 2006 allotments and the preliminary FY 2007 allotments determined under
      this methodology. We are also confirming the April 28, 2006 interim final rule as
      final.

PMID- 17042100
TI  - Assessment of FFR-negative intermediate coronary artery stenoses by spectral
      analysis of the radiofrequency intravascular ultrasound signal.
AB  - BACKGROUND: Assessing the clinical importance of angiographically intermediate
      coronary artery stenoses at the time of cardiac catheterization remains a
      challenge. Spectral analysis of radiofrequency ultrasound backscatter signals, or
      virtual histology (VH), allows in vivo assessment of plaque composition. This
      study characterizes the VH composition of fractional flow reserve (FFR)-negative
      intermediate stenoses and adjacent vessel segments. METHODS: Intermediate
      coronary artery stenoses (> 40% and < 70% diameter stenosis) were assessed by
      pressure wire. If the FFR was > or = 0.75, percutaneous coronary intervention was
      deferred and VH was performed on the lesion and adjacent segments using a
      commercially available system. The primary clinical endpoint was any adverse
      cardiac event. RESULTS: Thirty-seven intermediate stenoses in 30 patients were
      studied. The reference vessel size was 3.02 +/- 0.71 mm, the QCA diameter
      stenosis was 52 +/- 6% and the FFR was 0.89 +/- 0.07. The target stenoses were
      characterized by VH as: thin-cap fibroatheroma (VH-TCFA; n = 22); fibrous cap
      atheroma (n = 5), fibrocalcific lesion (n = 7) and pathological intimal
      thickening (n = 3). The relative contribution of each stenosis plaque component
      was conserved across adjacent segments ("signature" plaque). Three patients, all
      with VH-TCFAs at index, had events in the clinical follow-up period of 12 +/- 2
      months, but only 1 of these patients had an event related to the index stenosis.
      CONCLUSIONS: FFR-negative intermediate stenoses have heterogeneous plaque by VH,
      but are enriched in VH-TCFAs. Relative plaque composition is conserved along
      adjacent vessel segments. Although the specificity of VH-TCFA for index stenosis
      related events appears low, larger trials are needed to assess the prognostic
      value of VH in this lesion subset.

PMID- 17042101
TI  - Balloon alignment T-stenting for bifurcation coronary artery disease using the
      sirolimus-eluting stent.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term outcomes of
      bifurcation coronary lesions treated with a novel technique called "balloon
      alignment T-stenting". BACKGROUND: The optimal technique for the treatment of
      bifurcation coronary disease has not yet been established. METHODS: Twenty-six
      patients with bifurcation coronary lesions were treated with currently available
      drug-eluting stent (DES) platforms. This was a pilot study to determine the long
      term efficacy of a novel technique, "balloon alignment T-stenting". Based on this
      technique we performed 6-month anniversary angiography to determine restenosis
      rates for both main and side branch lesions treated. RESULTS: Twenty-six main
      branches and 27 side branches were treated with this novel technique.
      Angiographic 6-month follow up was available for all 26 patients treated. There
      were no postprocedural mortalities and no cases of postprocedural stent
      thrombosis during the follow-up period. At 6-month anniversary angiography, no
      evidence of main branch restenosis was seen. However, there were 2 cases of side
      branch restenosis for a total side branch restenosis rate of 7.4%. Target lesion
      revascularization for the 26 patients in the study was 7.6%. The total major
      adverse cardiac event rate for the group as a whole was 15.4%, with 2
      periprocedural non-Q-wave myocardial infarctions and 2 target lesions requiring
      revascularization at 6 months. CONCLUSION: Using currently available DES
      platforms, the data compiled from this small, single-center pilot study suggest
      that balloon alignment T-stenting may represent a reasonable approach for the
      treatment of bifurcation coronary artery disease. However, more comprehensive,
      larger-scale trials will be required to validate these preliminary findings.

PMID- 17042102
TI  - Titanium and nitride oxide-coated stents and paclitaxel-eluting stents for
      coronary revascularization in an unselected population.
AB  - The aim of this study was to compare clinical outcome of a stainless-steel stent
      coated with titanium nitride oxide (TITANOX) and a paclitaxel-eluting stent (PES)
      in routine clinical practice represented by two prospective registries including
      all patients with de novo coronary artery disease treated exclusively with a
      TITANOX stent (n = 201) or with a PES (n = 204) between May 2003 and November
      2004 (63% of all PCI patients). The primary endpoint of the study was major
      adverse cardiac events (MACE) at 30 days and 12 months. The TITANOX stent
      patients were more frequently (p = 0.011) treated for acute myocardial infarction
      and had more complex B- and C-type lesions (p = 0.004). The PES patients had
      longer (p < 0.001) total stent length. At 30 days, the rate of MACE was 0% and
      4.9% for the TITANOX stent and PES groups, respectively (p = 0.001). A
      significant difference in target vessel revascularization (TVR) was seen in favor
      of the TITANOX stent (0% vs. 2.9% for PES; p = 0.014). This was mainly driven by
      stent thrombosis (n = 7). At 12 months, the difference in MACE was no longer
      significant (10.9% vs. 13.7%; p = 0.40), but the rate of myocardial infarction
      was lower in the TITANOX stent group (4.5% vs. 10.3%; p = 0.025). The rate of TVR
      (8% vs. 6.9%; p = 0.67) was similar between the two groups. In conclusion, both
      the TITANOX-coated stent and PES resulted in good clinical outcome with
      infrequent need for repeat interventions in the real-world setting of high-risk
      patients and complex coronary lesions.

PMID- 17042103
TI  - Automated contrast injection in contemporary practice during cardiac
      catheterization and PCI: effects on contrast-induced nephropathy.
AB  - OBJECTIVES: To evaluate the incidence of contrast-induced nephropathy (CIN) with
      the use of an automated contrast injection system in conjunction with
      contemporary measures to prevent CIN after cardiac catheterization and
      percutaneous coronary intervention (PCI). BACKGROUND: The use of automated
      contrast injection systems can reduce the volume of procedural contrast, but
      whether lower contrast volume is associated with a lower incidence of CIN is
      uncertain. METHODS: The incidence of CIN was assessed in 1,798 patients after
      diagnostic catheterization or PCI at Wake Forest University Baptist Medical
      Center from April 2002 to November 2004 using traditional handheld manifold
      injection systems, and in 377 subsequent patients using an automated contrast
      injection system. Preprocedural hydration was used on a routine basis, and N
      acetylcysteine and bicarbonate infusion were used on an ad hoc basis. Outcomes
      were adjusted by standard logistic regression modeling. RESULTS: Mean contrast
      volume (+/- standard deviation) per case was reduced from 204 +/- 147 ml to 146
      +/- 108 ml, p < 0.05 by use of automated contrast injection. The incidence of CIN
      was 19.3% using manifold injection, and was 13.3%, p < 0.05, after use of
      automated contrast injection. The use of automated contrast injection was
      associated with a reduced relative risk of CIN, 0.66 (0.47-0.93), compared to
      manual injection, even after adjustment for baseline clinical and procedural
      covariates. CONCLUSIONS: The use of an automated contrast injection system in
      conjunction with contemporary hydration and pharmacologic strategies to prevent
      CIN during diagnostic catheterization and PCI was associated with a significant
      reduction in the use of contrast volume, as well as in the incidence of CIN.

PMID- 17042104
TI  - R (on the application of Quintavalle) v Secretary of State for Health.

PMID- 17042105
TI  - R (Quintavalle) v Human Fertilisation and Embryology Authority (Secretary of
      State for Health Intervening).

PMID- 17042106
TI  - R (on the application of Quintavalle) v Human Fertilisation and Embryology
      Authority.

PMID- 17042107
TI  - R (On the application of Quintavalle) v Secretary of State for Health.

PMID- 17042108
TI  - AB v Leeds Teaching Hospital NHS Trust.

PMID- 17042109
TI  - The grapes of wrath.

PMID- 17042110
TI  - Microorganisms and clean energy.

PMID- 17042111
TI  - Not every cell is sacred: a reply to Charo.
AB  - Massimo Reichlin, in an earlier article in this journal, defended a version of
      the 'argument from potential' (AFP), which concludes that the human embryo should
      be protected from the moment of conception. But R. Alto Charo, in her essay
      entitled 'Every Cell is Sacred: Logical Consequences of the Argument from
      Potential in the Age of Cloning', claims that versions of the AFP like Reichlin's
      are vulnerable to a rather embarrassing problem: with the advent of human
      cloning, such versions of the AFP entail that every somatic cell in the human
      body ought to be protected. Since this entailment is clearly absurd, Charo
      argues, these versions of AFP should be rejected. I argue that the reasons Charo
      cites for believing in this entailment are inconclusive. For example, the four
      reasons she gives for doubting any differences between the nature of skin cells
      and zygotes are ultimately unconvincing. Against Charo, I maintain that there is
      a relevant distinction between the sort of potential possessed by the somatic
      cell and the sort of potential possessed by the early human embryo. Since only
      the latter sort of potential falls within the scope of the AFP, the alleged
      absurd entailment Charo invites us to consider is no entailment at all. Hence the
      AFP cannot be rejected on the grounds Charo advances. Even in an age of cloning,
      the claim that some cells are 'sacred' because of their potential does not entail
      the claim that every cell is sacred.

PMID- 17042112
TI  - Should children and adolescents be tested for Huntington's disease? Attitudes of
      future lawyers and physicians in Switzerland.
AB  - The objective of the study was to identify future lawyers' and physicians' views
      on testing children for Huntington's disease (HD) against parents' wishes. After
      receiving general information about HD, patient autonomy and confidentiality, law
      students and advanced medical students were shown an interview with a mother
      suffering from HD who is opposed to informing and testing her two children (aged
      10 and 16) for HD. Students then filled out questionnaires concerning their
      agreement with testing. No significant differences were found between medical and
      law students or between students from different courses concerning the adolescent
      son. Three quarters of students thought that he should be told about his mother's
      disease, and 91% thought the adolescent son should have the opportunity of
      genetic testing for HD himself. However, significant differences were found
      concerning the 10-year old son, with 44% of law students and 30% of medical
      students in favour of testing the child for HD. Students raised some important
      ethical issues in their elective comments. In conclusion, we found highly
      positive attitudes towards informing a 16-year old of his mother's HD and
      offering to test him. These attitudes were not in tune with guidelines. Students
      did not consider several practical and ethical issues of genetic testing of
      children and adolescents. Specific education should ensure that attitudes are
      based on sufficiently detailed knowledge about all aspects of genetic testing of
      children to discourage pressures on persons at risk of HD.

PMID- 17042113
TI  - Inconsistencies in pro ANT-OAR position.

PMID- 17042114
TI  - Prospects for pluripotent stem cells: a reply to Communio.

PMID- 17042115
TI  - A contralife argument against altered nuclear transfer.

PMID- 17042116
TI  - The embryo as person.

PMID- 17042117
TI  - Freedom at the end of life: voluntary death versus human flourishing.

PMID- 17042118
TI  - Euthanasia: an uncontrollable power over death.

PMID- 17042119
TI  - Welcoming the child at birth.

PMID- 17042120
TI  - A case studies approach to assisted nutrition and hydration.

PMID- 17042121
TI  - Human cloning and embryonic stem cell research after Seoul: examining
      exploitation, fraud and ethical problems in the research. Testimony of Richard M.
      Doerflinger.

PMID- 17042122
TI  - Terrorism and dispelling the myth of a panic prone public.
AB  - Governments and commentators perceive the public to be prone to panic in response
      to terrorist attacks--conventional or involving chemical, biological or
      radiological weapons. Evidence from five such incidents suggests that the public
      is not prone to panic, although people can change their behaviours and attitudes
      to reduce the risk of themselves being exposed to a terrorist incident.
      Behavioural responses may be divided into acts of omission, such as not making
      unnecessary journeys, and acts of commission, such as taking prophylactic
      medication despite the inherent risk of side effects. Evidence suggests that the
      public are aware of these differences, and tend to adopt responses proportionate
      to the risk. Drawing upon the literature in the social and natural sciences, our
      discussion encompasses differing risk perceptions of terrorist threats and
      consequences of attacks. How do fear and anxiety interact with behavioural
      responses to amplify or attenuate perceptions that can be modified through risk
      communication undertaken by authorities?

PMID- 17042123
TI  - The effects of obesity on doctor-diagnosed chronic diseases in Africa: empirical
      results from Senegal and South Africa.
AB  - While inadequate food and communicable infectious diseases have been a concern of
      researchers and policy makers in Africa, little attention has been given to
      obesity and chronic, non-communicable diseases. Africa is not usually associated
      with obesity and chronic diseases. Yet there has been a sharp rise in the
      incidence of obesity and chronic diseases, a major public health problem in many
      countries. The paper examines the impact of obesity on the prevalence of four
      doctor-diagnosed chronic diseases in Senegal and South Africa. The results reveal
      that obese respondents were 4.7, 2.8, and 4.8% more likely to face the risks of
      arthritis, diabetes, and heart diseases in South Africa and 6.5 and 7.4% more
      likely to face the risks of heart disease and asthma in Senegal than their lean
      counterparts. Obesity imposes a real and substantial danger, affecting the
      prevalence of chronic diseases. Unchecked it can be a major public health
      problem, impose a serious challenge to the health sector, and can jeopardize
      future developments.

PMID- 17042124
TI  - Setting health priorities across nations: more convergence than divergence?
AB  - Recently, various theories of convergence of health care systems have been
      presented. This review of several dimensions of health priority setting in nine
      countries sheds light on the interrelationship between convergence and
      embeddedness. It reconfirms that within a co-existence of convergence and
      divergence, there are clusters of convergence, primarily at the ideational and
      social value levels. However, our findings suggest that the variation across
      different substantive levels is less clear cut than suggested by others.
      Moreover, the variation between different procedural aspects of convergence
      appears more significant. Certain ideas involving the need for rationing, the
      role of market mechanisms, and cost containment have gained recognition by health
      policy makers across countries, but this has not guaranteed their adoption. Our
      analysis demonstrates that despite these signs of a convergence at the conceptual
      level, policy content and the preferred policy instruments for implementing such
      policy continue to vary widely across these countries.

PMID- 17042125
TI  - Evidence against breast self examination is not conclusive: what policymakers and
      health professionals need to know.
AB  - Breast cancer is a serious health concern and a disease that is not well
      understood. Early detection remains the best way to prevent debilitation and
      death. Traditionally, mammography, clinical breast examination (CBE), and breast
      self examination (BSE) have been accepted as legitimate breast screening
      modalities. Over the past 5 years, academics, health professionals, and
      policymakers have seriously questioned the usefulness of BSE after influential
      organizations such as the Canadian Task Force on Preventive Health Care
      downgraded their BSE recommendation citing fair evidence of no benefit and good
      evidence of harm. We briefly review the three large BSE trials, highlighting
      methodological weaknesses limiting their ability to evaluate its effectiveness,
      as well as critique the 2001 Canadian Task Force on Preventive Health Care report
      on BSE. We argue that it is premature to conclude that BSE is ineffective. Given
      that most women find their own breast cancer, this article cautions policymakers
      and health professionals that a prudent approach to BSE promotion should be
      taken.

PMID- 17042126
TI  - Policy needs regarding the duty to protect in epidemiological research with high
      risk populations.
AB  - The paper presents an analysis of policy directives needed to respond to threats
      of harm (e.g., violence against third parties) that may arise in the course of
      conducting descriptive epidemiological research with high-risk populations. It
      identifies two key areas where new policies must be developed to guide
      researchers conducting such investigations. The paper recommends that: (1) an NIH
      consensus panel be convened to set standards, analogous to Common Toxicity
      Criteria (CTC) criteria, to classify the severity of different types of indirect,
      non-research-related risk; and (2) case-based training modules be developed and
      incorporated into public health research ethics courses and training programs, to
      enhance researcher judgments in determining the likelihood of harm in different
      situations. In addition, researchers, Institutional Review Boards (IRBs) and
      community advisory groups must consider the issue of staff safety and the
      effectiveness of available responses to reduce the threat of harm. The author
      reviews and discusses implications for informed consent and IRB review.

PMID- 17042127
TI  - The Federation's Pages. Public health workforce, the new role.

PMID- 17042128
TI  - Lombardy poplar.

PMID- 17042129
TI  - Specific polysaccharide antibody deficiency.

PMID- 17042130
TI  - Pathogenesis and recent therapeutic trends in Stevens-Johnson syndrome and toxic
      epidermal necrolysis.
AB  - OBJECTIVE: To review the current pathophysiologic mechanisms and recent
      therapeutic trends in Stevens-Johnson syndrome (SJS) and toxic epidermal
      necrolysis (TEN). DATA SOURCES: A MEDLINE search for SJS and TEN in combination
      with Fas, Fas ligand (FasL), cytotoxic T cells, intravenous immunoglobulin, and
      cyclosporine for articles published in English during 1966 to 2006. STUDY
      SELECTION: Information was derived from original research articles and reviews
      published in peer-reviewed journals. RESULTS: The hallmark of SJS and TEN is
      epidermal cell apoptosis, which may be mediated through keratinocyte Fas-FasL
      interaction or through cytotoxic T-cell release of perforin and granzyme B.
      Whereas systemic corticosteroid therapy showed contradictory results, intravenous
      immunoglobulin (IVIG) and cyclosporine have shown promising outcomes. IVIG
      contains anti-Fas antibodies that can abrogate apoptosis when preincubated with
      keratinocytes. Most studies on IVIG in SJS and TEN reported improvement in
      arresting disease progression and reduction in time to skin healing. Because of
      variations among studies, the findings cannot be optimally compared. In general,
      mortality varied from 0% to 12% in studies that supported the use of IVIG and 25%
      to 41.7% in those that did not demonstrate a beneficial effect. Cyclosporine
      inhibits CD8 activation and thus may reduce epidermal destruction. Relatively few
      case reports and 1 case series have been published regarding the use of
      cyclosporine in SJS and TEN. In general, cyclosporine was associated with a
      significant improvement in time to disease arrest and to complete
      reepithelization, with no reported fatalities. CONCLUSIONS: Both IVIG and
      cyclosporine have been associated with enhanced healing and better survival
      through inhibition of apoptosis. Multicenter, randomized, placebo-controlled
      trials using a standardized design are needed to validate these findings.

PMID- 17042131
TI  - Lack of cross-reactivity between 5-aminosalicylic acid-based drugs: a case report
      and review of the literature.
AB  - BACKGROUND: 5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of
      therapy in inflammatory bowel disease, but adverse reactions to these medications
      are relatively common. Because there may be a lack of cross-reactivity among the
      various 5-ASA formulations, treatment with alternative preparations is sometimes
      possible even after an apparent allergic reaction to a 5-ASA product. OBJECTIVE:
      To describe a patient with a possible allergy to 2 different 5-ASA drugs who
      tolerated a third. METHODS: A 27-year-old man with Crohn disease developed a rash
      while taking mesalamine (Pentasa and Asacol). Treatment with 5-ASA products was
      discontinued, and 6-mercaptopurine and prednisone were prescribed. He then
      experienced multiorgan failure secondary to herpes simplex infection, which
      required discontinuation of the immunosuppressive therapy. After recovery from
      the acute infection, he underwent successful graded challenge with balsalazide.
      RESULTS: The patient continued treatment with balsalazide for 9 months, with good
      control of his inflammatory bowel disease and no adverse effects. CONCLUSIONS:
      Adverse reactions to 1 or more 5-ASA medications do not necessarily preclude the
      use of others in the same class. A treatment algorithm for patients with adverse
      reactions to 5-ASA is outlined based on the case report and review of the
      literature.

PMID- 17042132
TI  - Improvement of asthma control with omalizumab in 2 obese pediatric asthma
      patients.
AB  - BACKGROUND: Dosing of the anti-IgE antibody (omalizumab) in the treatment of
      allergic asthma depends on serum IgE concentration and body weight. It is unclear
      whether omalizumab is therapeutically effective in obese patients with difficult
      to-control asthma whose body weights fall outside dosing guidelines. OBJECTIVE:
      To report the efficacy of omalizumab in 2 obese pediatric patients with severe
      persistent asthma whose high body weights placed them outside current dosing
      guidelines. METHODS: Omalizumab was given at maximum doses to both patients.
      Standard asthma therapy was continued throughout the treatment period. Multiple
      parameters of asthma disease activity were followed at every health encounter for
      approximately 1 year during and before omalizumab treatment. These parameters
      included asthma disease severity and activity, pulmonary functions, daily inhaled
      corticosteroid requirements, systemic steroid rescue, and urgent care and
      emergency department visits and hospitalizations. RESULTS: While receiving
      omalizumab, both patients had improvements in asthma disease activity and
      reduction in systemic steroid requirements. One patient required fewer daily
      inhaled corticosteroids and achieved total asthma control. CONCLUSION: Patients
      with difficult-to-treat asthma may benefit from receiving omalizumab even if they
      fall outside current dosing guidelines because of high body weight.

PMID- 17042133
TI  - Clustered sensitivity to fungi: anaphylactic reactions caused by ingestive
      allergy to yeasts.
AB  - BACKGROUND: Respiratory allergy to environmental molds is relatively common, and
      fungal allergen-specific reactivity seems to cluster in certain persons. However,
      generalized reactions caused by ingested fungi have seldom been described.
      OBJECTIVE: To describe a mold-sensitized patient who developed multiple
      anaphylactic reactions after ingesting a yeast preparation widely used by the
      food industry as flavoring in, for example, powdered and ready-made sauces.
      METHODS: Skin prick tests and serum IgE tests were performed with inhalant and
      food allergens, including molds and yeasts, 2 pasta sauces consumed by the
      patient, individual sauce ingredients, and a food-quality yeast extract.
      Radioallergosorbent test inhibition was used for specificity studies. RESULTS:
      Skin prick and serum IgE test results were positive to several molds
      (Cladosporium herbarum, Alternaria alternata, Aspergillus fumigatus, and
      Penicillium notatum), baker's yeast (Saccharomyces cerevisiae), Malassezia
      furfur, and champignon and to the 2 pasta sauces, the yeast ingredient, and a
      food-quality yeast extract. Radioallergosorbent test inhibition studies confirmed
      that the sauces contain cross-reacting yeast and mold allergens. CONCLUSIONS:
      This patient has a clustered sensitization to fungi characterized by allergy to
      environmental fungal allergens and to yeast extracts used in the food industry.
      Yeasts should be considered as possible ingestive allergens in mold-allergic
      patients.

PMID- 17042134
TI  - Use of the health plan employer data and information set for measuring and
      improving the quality of asthma care.
AB  - OBJECTIVES: To discuss the Health Plan Employer Data and Information Set (HEDIS)
      criteria for measuring performance in asthma care and to review new strategies to
      improve the quality of asthma care. DATA SOURCES: Expert opinion from a
      roundtable on National Committee for Quality Assurance HEDIS and asthma care,
      supplemented with a MEDLINE database search to identify articles published
      between January 1, 1990, and May 31, 2005, with the following keywords in the
      title: asthma plus HEDIS, pay for performance, incentive programs, reimbursement,
      or employee education. STUDY SELECTION: Studies and review articles were selected
      for their relevance to measuring the quality of asthma care using HEDIS and
      improving care using newer trends, such as employee education and physician
      incentive programs. RESULTS: Components of the HEDIS asthma measure have been
      found to correlate with outcomes, including risk of hospitalization and emergency
      department visits. However, refinements to the measure may be needed because it
      may misclassify a portion of patients as having persistent asthma who actually
      have intermittent asthma according to National Heart, Lung, and Blood Institute
      criteria. Physician incentive programs are increasingly being explored as a means
      of improving the quality of care while managing costs. Under current pay-for
      performance programs, rewards are issued to providers who demonstrate high
      quality care based on the HEDIS asthma measure. CONCLUSIONS: The HEDIS asthma
      measure remains the most widely used performance tool for evaluating the quality
      of asthma care. Reimbursement models based on public reporting and pay for
      performance are expected to be a strong component of future health care payment
      systems.

PMID- 17042135
TI  - Clinical and laboratory characteristics of 75 patients with specific
      polysaccharide antibody deficiency syndrome.
AB  - BACKGROUND: There are limited studies of large cohorts of patients with specific
      polysaccharide antibody deficiency (SPAD) syndrome. OBJECTIVE: To study the
      clinical and laboratory characteristics of patients with specific polysaccharide
      antibody deficiency syndrome. METHODS: We retrospectively studied 75 patients
      with total IgG levels of at least 500 mg/dL and fewer than 9 of 12 responses to
      vaccination with pneumococcal vaccine polyvalent. Exclusion criteria included an
      IgG level less than 500 mg/dL, established immunodeficiency syndrome, and
      secondary immunodeficiency. RESULTS: The most common clinical presentation was
      frequent infections (n = 69; 92%), including sinusitis (n = 53; 77%), pneumonia
      (n = 29; 42%), ear infections (n = 18; 26%), and bronchitis (n = 19; 28%). Other
      presentations were systemic infections (n = 5; 7%), autoimmune or rheumatic
      diseases (n = 6; 8%), and chronic diarrhea (n = 4; 5%). The median IgG2 level of
      patients with no response to pneumococcal vaccine polyvalent tended to be lower
      than that of patients with at least 1 response (150 vs 193 mg/dL, respectively; P
      = .06). There was no association between total IgG level (categorized as 500-600
      or > or = 600 mg/dL) and frequency of infection (P = .43). Patients with fewer
      responses to pneumococcal vaccine polyvalent and a higher frequency of infections
      were more likely to receive intravenous immunoglobulin (IVIG) therapy (P = .01
      and .003, respectively). Treatment with IVIG significantly reduced the number of
      infections (P < .001). CONCLUSION: Patients with no response to pneumococcal
      vaccine polyvalent tended to have lower IgG2 levels; those with fewer responses
      were more likely to receive IVIG therapy.

PMID- 17042136
TI  - Profiles of proinflammatory cytokines in sputum from different groups of severe
      asthmatic patients.
AB  - BACKGROUND: Severe asthma represents a heterogeneous group of patients whose
      characteristics of airway inflammation are poorly known. OBJECTIVE: To evaluate
      the sputum cytokine profiles of different phenotypes of severe asthma. METHODS:
      Severe asthmatic patients (n = 45) were divided into 3 groups: frequent
      exacerbations, persistent bronchoconstriction, and both features. Two other
      groups (9 patients with untreated mild asthma and 10 control subjects) were also
      studied. Selected sputum portions were assayed for differential cell count,
      supernatant interleukin 5 (IL-5), granulocyte-macrophage colony-stimulating
      factor, IL-8, and eosinophil cationic protein. RESULTS: There were no
      statistically significant differences among the 3 severe asthma groups in terms
      of sputum inflammatory cell percentages, IL-8 levels, and eosinophil cationic
      protein levels, although IL-8 levels tended to be higher in patients with
      persistent bronchoconstriction. Sputum concentrations of granulocyte-macrophage
      colony-stimulating factor and IL-5 were significantly higher in patients with
      frequent exacerbations compared with the other 2 groups. Levels of IL-5 and IL-8
      were higher in severe asthmatic patients compared with mild asthmatic patients
      and controls, whereas sputum eosinophil percentages were intermediate between
      those of mild asthmatic patients and controls. CONCLUSIONS: Proeosinophilic
      cytokine levels are increased in severe asthmatic patients with frequent
      exacerbations but not in severe asthmatic patients with persistent
      bronchoconstriction, suggesting that different cytokine profiles could be
      associated with different phenotypes of severe asthma.

PMID- 17042137
TI  - The effect of CD14-c159T genotypes on the cytokine response to endotoxin by
      peripheral blood mononuclear cells from asthmatic children.
AB  - BACKGROUND: A C-T polymorphism at position 159 in the promoter of CD14 (C-159T)
      modulates the cellular response to endotoxin and significantly influences total
      IgE levels. The effect of this genetic variant on the cytokine response of the
      inflammatory cells is incompletely understood. OBJECTIVE: To investigate the
      effects of CD14-C159T genotypes on the response to endotoxin by peripheral blood
      mononuclear cells (PBMCs) in children with asthma. METHODS: The PBMCs from
      asthmatic children with the TT (n = 11) and CC (n = 11) genotypes at the CD14
      promoter were cultured in the presence of endotoxin, 100 ng/mL; concanavalin A,
      10 microg/mL; or medium alone. Concentrations of soluble CD14 (sCD14),
      interleukin (IL) 1beta, IL-4, IL-10, IL-12, IL-13, interferon-gamma, and
      transforming growth factor beta were determined in culture supernatants by enzyme
      linked immunosorbent assay, and the transcriptional differences were evaluated
      using reverse-transcriptase polymerase chain reaction. RESULTS: Under
      unstimulated conditions, children with the TT genotype produced higher levels of
      sCD14 into the culture supernatant compared with children with the CC genotype (P
      = .03, Mann Whitney U test). Both IL-10 and IL-1beta concentrations were
      significantly higher in culture supernatants of children with the TT genotype
      after endotoxin stimulation (P = .02 and P = .009, respectively, by analysis of
      covariance [ANCOVA]). Messenger RNA expression was consistent with the results of
      protein concentration for IL-10 and sCD14. Concanavalin A stimulation resulted in
      lower levels of IL-4 in children with the TT genotype (P = .02, ANCOVA).
      CONCLUSION: The genotype at the CD14 promoter C159T locus may significantly
      influence the cytokine response of PBMCs obtained from asthmatic children.
      Differences in IL-10 and IL-4 production by alternative genotypes may contribute
      to the observed genotype effect on total IgE.

PMID- 17042138
TI  - Effect of montelukast on bacterial sinusitis in allergic mice.
AB  - BACKGROUND: In mice, allergic rhinitis augments the infectious and inflammatory
      response to Streptococcus pneumoniae-induced sinusitis. OBJECTIVE: To investigate
      the effects of cysteinyl leukotriene antagonism on the severity of bacterial
      infection. METHODS: We performed 3 parallel, placebo-controlled experiments. In
      the first, mice were ovalbumin sensitized and ovalbumin challenged to show the
      effects of montelukast on the allergic inflammation; in the second, we evaluated
      the effect of montelukast on S. pneumoniae infection; in the third, we used mice
      that were both allergic and infected. Montelukast was given starting 2 days after
      sensitization until the day before euthanasia. One day after drug treatment
      began, the mice were inoculated intranasally with S. pneumoniae in the infected
      groups. Nasal hypersensitivity was measured with histamine challenges before the
      first sensitization and on the day before euthanasia. On the fifth day after
      infection, mice were euthanized, nasal lavage was performed, bacteria were
      cultured, and inflammatory cells in the sinuses were quantified. RESULTS: Mice
      that were infected only tended toward having increased bacterial counts from
      nasal lavage in the montelukast-treated group. The mice that were allergic and
      infected experienced significantly higher bacterial counts (P < .05). All 3
      montelukast treatment groups had significantly decreased eosinophil counts as
      well as T-lymphocyte counts. CONCLUSIONS: Montelukast reduces the manifestations
      of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in
      bacterial growth in infected mice. This suggests an effect of the cysteinyl
      leukotrienes on the innate response to bacterial infection.

PMID- 17042140
TI  - Allergenic proteins in Urtica dioica, a member of the Urticaceae allergenic
      family.
AB  - BACKGROUND: Allergy to the pollen of flowering plant species significantly
      affects the health of people in many parts of the world. Pollens of related
      genera usually share common antigens and are often, but not always, cross
      reactive. Several studies have shown that Parietaria pollen is one of the most
      common causes of pollinosis in the Mediterranean area, whereas Urtica has no
      allergenic significance. OBJECTIVES: To report on the localization of Parietaria
      judaica major allergen in Urtica dioica pollen grains and on the detection of
      allergenic proteins in U. dioica pollen grains during the hydration-activation
      process. METHODS: A combination of transmission electron microscopy and
      immunocytochemical methods was used to locate allergenic proteins in U. dioica
      pollen grains after different periods of hydration-activation using the anti-Par
      j 1 (4.1.3.) monoclonal antibody and serum samples from allergic patients.
      RESULTS: No significant labeling was noted for Parj 1 allergen after 10, 15, and
      20 minutes in the walls and cytoplasm. Slight labeling was observed for allergic
      proteins in the walls of U. dioica after 10 minutes of hydration, and no
      significant labeling was found after 15 and 20 minutes of hydration. CONCLUSIONS:
      Immunocytochemical methods confirmed the absence of cross-reactivity between 2
      related genera, Parietaria and Urtica, and the lowest allergenic potential of U.
      dioica.

PMID- 17042139
TI  - Identification of italian cypress (Cupressus sempervirens) pollen allergen Cup s
      3 using homology and cross-reactivity.
AB  - BACKGROUND: The prevalence of seasonal allergic diseases of the upper airways is
      increasing in industrialized countries. The Cupressaceae are important causes of
      pollinosis, particularly in Europe. OBJECTIVE: To determine whether the pollen
      from Cupressus sempervirens (Italian cypress) contains a pathogenesis-related
      group 5 (PR-5) protein, similar to that found in other allergenic Cupressaceae
      pollens. METHODS: Messenger RNA was purified from Italian cypress pollen, and
      complementary DNA (cDNA) was synthesized. cDNAs for PR-5 proteins were amplified
      by polymerase chain reaction and extended by rapid amplification of cDNA ends
      methods. Recombinant Cup s 3 was expressed in Escherichia coli as a fusion
      protein. Inhibition enzyme-linked immunosorbent assays were used to test the
      allergenicity of Cup s 3. RESULTS: Three cDNAs were cloned. These clones had
      approximately 95% identity to Jun a 3 and Cup a 3. Recombinant Cup s 3.0102
      maltose-binding protein inhibited the IgE from most patients from binding to an
      extract of Italian cypress. The extent of inhibition suggested that antibodies to
      Cup s 3 were a prominent component of the IgE response to Italian cypress pollen.
      CONCLUSION: Cup s 3, an allergen of Italian cypress pollen, was identified based
      on cross-reactivity and homology with other pollen PR-5 proteins, despite an
      apparently low level of protein expression. Variations in the content of Cup s 3
      in the pollen from different regions or trees should be considered in the choice
      of extracts for diagnosis and specific immunotherapy for Italian cypress pollen
      hypersensitivity.

PMID- 17042141
TI  - Comparison of enzyme immunoassay-based assays for environmental Alternaria
      alternata.
AB  - BACKGROUND: Alternaria alternata-derived allergenic materials are causes of human
      disease. Several immunoassays exist to quantify these materials. OBJECTIVE: To
      compare methods for evaluating Alternaria content. METHODS: Four methods,
      including 1 monoclonal antibody (MAb)-based assay specific for recombinant Alt a
      1, 1 MAb-based assay for chromatographically purified Alt a 1, 1 polyclonal
      antibody (PAb)-based assay for chromatographically purified Alt a 1, and 1 PAb
      based assay for whole Alternaria extract, were evaluated. Environmental samples
      collected as part of the National Survey of Lead and Allergens in Housing were
      examined. Alternaria spore counts were determined in dust by observation.
      RESULTS: The MAb-based assay for recombinant Alt a 1 detected Alternaria in few
      samples (25%); the PAb-based assay for whole Alternaria proteins detected antigen
      in 97% of the samples. The PAb- and MAb-based assays for purified Alt a 1
      detected antigen in 100% of the samples. There was a significant positive
      correlation between the 2 assays directed against purified Alt a 1. There was a
      positive correlation between the PAb-based assay for whole Alternaria and the PAb
      based assay for Alt a 1. Nearly all the dust samples contained Alternaria spores,
      and there was a strong positive correlation between counts and all assays.
      CONCLUSION: Because of the multifaceted nature of Alternaria, the disparities
      between methods for quantifying Alternaria, the cross-reactivity between fungal
      allergens, and the documented genetic promiscuity of this fungus, enzyme
      immunoassays using PAbs against a range of Alternaria proteins will probably
      produce the most reliable estimation of overall Alternaria exposure in house
      dust.

PMID- 17042143
TI  - Use of complementary and alternative medicine by food-allergic patients.
AB  - BACKGROUND: Interest in complementary and alternative medicine (CAM) is
      increasing. Use of CAM in food-allergic patients has not previously been
      evaluated. OBJECTIVES: To determine the prevalence of CAM use, the types of CAM
      modalities used, and opinions about CAM in food-allergic patients. METHODS: A
      questionnaire was distributed to attendees at a patient conference in 2002 and to
      patients at pediatric food allergy clinics in 2005. RESULTS: Surveys were
      completed by 380 families. Respondents were mainly white, parents of children
      with multiple food allergies, and from the tri-state (New York, New Jersey,
      Connecticut) area. Diagnostic modalities considered unproven or disproven (such
      as serum IgG4, electrodermal skin testing, and kinesiology) were used by 22% of
      respondents; CAM therapies were used by 18%. Participants used several types of
      CAM practitioners, the most common being chiropractors, homeopaths, and
      acupuncturists. Only 49% of patients using CAM disclosed this to their
      physicians. Efficacy ratings for CAM were poor. Regarding participants' opinions,
      an herbal therapy of equal efficacy, safety, and cost was preferred to a
      pharmaceutical drug (37% vs 12%; P = .001), but most participants (51%) had no
      preference or were unsure. CONCLUSION: Unproven or disproven diagnostic methods
      and CAM treatments were used by approximately 1 in 5 respondents. Those using CAM
      noted poor efficacy, but if given a choice, many would prefer herbal therapies to
      pharmaceutical drugs. Education regarding reliable testing for food allergy and
      further research on CAM therapies are warranted.

PMID- 17042142
TI  - Evaluation of antibody binding to diisocyanate protein conjugates in a general
      population.
AB  - BACKGROUND: Specific IgG binding to diisocyanate-human serum albumin (HSA) has
      been proposed as an indicator of diisocyanate exposure. One residential study
      reported IgG binding to diisocyanate conjugates in 8% of residents living near a
      factory using toluene diisocyanate (TDI). Because comparable assays were not
      performed using individuals distant from such facilities, the significance of
      this finding is uncertain. OBJECTIVE: To determine the prevalence of diisocyanate
      specific antibodies in sera from individuals "not known to be exposed" to
      diisocyanates. METHODS: Serum samples from 139 anonymous donors without known
      diisocyanate exposure were assayed by means of enzyme-linked immunosorbent assay
      for IgG or IgE specific for TDI-HSA, diphenylmethane diisocyanate (MOI)-HSA, and
      hexamethylene diisocyanate (HDI)-HSA. Positive responses (optical density > or =
      0.1 and > or = 3 SDs above the mean of 8 laboratory controls) were run 3 times.
      Competitive inhibition was performed for sera exhibiting binding of optical
      density of at least 0.2. RESULTS: We detected IgG reactive with HDI-HSA,
      diphenylmethane diisocyanate-HSA, and TDI-HSA in 18 (13%), 0, and 7 donors (5%),
      respectively. Inhibition (>50%) was demonstrated in 6 of 9 participants with
      elevated HDI-HSA levels and in 2 of 7 with elevated TDI-HSA levels. We detected
      IgE reactive with the same antigens in 3 donors (2%); however, none were
      confirmed to be positive using the biotin-streptavidin IgE assay. CONCLUSIONS:
      Specific and nonspecific IgG binding to HDI-HSA and TDI-HSA were detected in
      individuals without known exposure to isocyanates. These antibody measurements
      may not be reliable indicators of diisocyanate exposure in nonoccupational
      populations and should not be interpreted as surrogates of diisocyanate exposure
      in the absence of defined referent populations.

PMID- 17042144
TI  - Fasting: an important issue in asthma management compliance.
AB  - BACKGROUND: Fasting, neither eating nor drinking anything between dawn (sahur
      time) and sundown (iftar time), may have an important role in the treatment and
      follow-up of asthmatic patients in countries where most of the population is
      Muslim. OBJECTIVE: To analyze the effects of fasting on outpatient asthmatic
      patients. METHODS: One hundred twenty-one fasting patients were evaluated for
      attendance at follow-up visits, attitudes about undergoing diagnostic
      investigations, and opinions and practices regarding medication use during
      fasting. Their sources of knowledge about asthma, fasting, and medication
      consumption were also evaluated. RESULTS: Ninety percent of fasting patients
      reported no harm with respect to religion of visiting physicians while fasting.
      Although 96% of the patients stated that inhaled medication could be used, only
      13% continued to use medication in the same manner as when they were not fasting.
      Most patients rearranged their medication-consumption hours. Although 96% of the
      patients received general information about asthma from their physicians, rates
      of receiving information about the fasting-medication use relationship from
      physicians and religious sources were similar (37% and 32%, respectively).
      CONCLUSION: Most Muslim asthmatic patients do not consider asthma to be a
      drawback to fasting, and they continue fasting by rearranging their medication
      consumption times. During Ramadan, patients should be questioned about this
      subject and should be followed up carefully for asthma control at regular visits.

PMID- 17042145
TI  - Impact of azelastine nasal spray on symptoms and quality of life compared with
      cetirizine oral tablets in patients with seasonal allergic rhinitis.
AB  - BACKGROUND: In fall 2004, the first Azelastine Cetirizine Trial demonstrated
      statistically significant improvements in the total nasal symptom score (TNSS)
      and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores with the use
      of azelastine nasal spray vs oral cetirizine in patients with seasonal allergic
      rhinitis (SAR). OBJECTIVE: To compare the effects of azelastine nasal spray vs
      cetirizine on the TNSS and RQLQ scores in patients with SAR. METHODS: This 2
      week, double-blind, multicenter trial randomized 360 patients with moderate-to
      severe SAR to azelastine, 2 sprays per nostril twice daily, or cetirizine, 10-mg
      tablets once daily. The primary efficacy variable was the 12-hour reflective TNSS
      (rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy
      variables were individual symptom scores and the RQLQ score. RESULTS: Azelastine
      nasal spray and cetirizine significantly improved the TNSS and individual
      symptoms compared with baseline (P < .001). The TNSS improved by a mean of 4.6
      (23.9%) with azelastine nasal spray compared with 3.9 (19.6%) with cetirizine.
      Significant differences favoring azelastine nasal spray were seen for the
      individual symptoms of sneezing and nasal congestion. Improvements in the RQLQ
      overall (P = .002) and individual domain (P < or = .02) scores were greater with
      azelastine nasal spray. Both treatments were well tolerated. CONCLUSIONS:
      Azelastine nasal spray and cetirizine effectively treated nasal symptoms in
      patients with SAR. Improvements in the TNSS and individual symptoms favored
      azelastine over cetirizine, with significant differences for nasal congestion and
      sneezing. Azelastine nasal spray significantly improved the RQLQ overall and
      domain scores compared with cetirizine.

PMID- 17042146
TI  - Effect of formoterol fumarate treatment on exercise-induced bronchoconstriction
      in children.
AB  - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is common, particularly in
      children. OBJECTIVES: To compare the protective effect of single doses of
      formoterol fumarate via Aerolizer with placebo and albuterol in children with
      EIB. METHODS: In this randomized, double-blind, double-dummy, crossover trial, 23
      children (aged 4-11 years) received formoterol, 12 or 24 microg; albuterol, 180
      microg; or placebo at 4 separate visits. Protection against EIB was evaluated as
      the maximum percentage decrease in forced expiratory volume in 1 second (FEV1)
      from the preexercise value after exercise challenge tests (6-minute treadmill)
      conducted 15 minutes and 4, 8, and 12 hours after administration of the dose.
      RESULTS: The maximum percentage decrease in FEV1 after the 4-hour exercise test
      (primary efficacy variable) was significantly less for formoterol, 12 and 24
      microg, vs placebo (P < .001 for both) or albuterol (P = .016 and .010,
      respectively); albuterol was not significantly different from placebo.
      Formoterol, 12 and 24 microg, differed from placebo at 8 hours (P = .002 and
      .001, respectively), with a smaller difference between albuterol and placebo (P =
      .045). Rescue medication use and a high dropout rate may have biased treatment
      differences at later time points. Protection against EIB (<20% maximum decrease
      in FEV1) across all time points was observed for 17 (77%) of 22 and 17 (74%) of
      23 children with formoterol, 12 and 24 microg, respectively, compared with 8
      (35%) of 23 with albuterol and 6 (27%) of 22 with placebo. CONCLUSIONS: Single
      doses of formoterol, 12 or 24 microg, are effective in protecting against EIB in
      children, affording a statistically significantly greater protective effect than
      placebo or albuterol.

PMID- 17042147
TI  - Comparison of cetirizine-pseudoephedrine and placebo in patients with seasonal
      allergic rhinitis and concomitant mild-to-moderate asthma: randomized, double
      blind study.
AB  - BACKGROUND: Allergic rhinitis (AR) and asthma are common concurrent conditions.
      OBJECTIVES: To evaluate the effects of cetirizine hydrochloride (5 mg)
      pseudoephedrine hydrochloride (120 mg) (cetirizine-D) twice daily on AR and
      asthma symptoms, pulmonary function, and asthma-related quality of life in 274
      patients with confirmed seasonal AR and concomitant mild-to-moderate asthma.
      METHODS: In this multicenter, randomized, double-blind, placebo-controlled study,
      after a 1-week screening period, patients took cetirizine-D or placebo for 4
      weeks. The primary efficacy variable, AR total symptom severity complex score,
      was derived from patient daily diary ratings of sneezing, runny nose, itchy nose,
      postnasal drip, and nasal congestion. Asthma symptom severity total scores were
      derived from twice-daily diary ratings of wheezing, coughing, shortness of
      breath, and chest tightness. Pulmonary function was tested at clinic visits and
      by patients each morning and evening. Patients completed the Asthma Quality of
      Life Questionnaire at each visit. All tests were 2-sided, with statistical
      significance at the .05 level. RESULTS: Cetirizine-D reduced total symptom
      severity complex scores by 42.3% overall vs 23.6% with placebo (P < .001). Asthma
      symptom severity total scores were significantly improved with cetirizine-D at
      most times vs placebo. Cetirizine-D treatment was also associated with
      significantly improved Asthma Quality of Life Questionnaire overall scores.
      Pulmonary function test results were neutral. Cetirizine-D was well tolerated,
      with discontinuation and adverse event rates similar to placebo. Somnolence
      occurred in 8 patients (5.8%) taking cetirizine-D and in 1 (0.7%) taking placebo.
      CONCLUSIONS: Treatment with cetirizine-D twice daily significantly reduced
      rhinitis and asthma symptoms and improved overall asthma quality of life in
      patients with seasonal AR and concomitant mild-to-moderate asthma.

PMID- 17042149
TI  - Medication compliance and disease exacerbation in patients with asthma: a
      retrospective study of managed care data.
AB  - BACKGROUND: Compliance with asthma medications probably results in improved
      outcomes, but few studies have examined this relationship. OBJECTIVE: To examine
      the association between medication compliance and exacerbation in asthmatic
      patients. METHODS: Retrospective analysis of a managed care database. The 97,743
      participants (aged 6-99 years; mean age, 32.8 years) had asthma and prescriptions
      for controller medications. Compliance with the index medication (the first
      controller medication prescribed) was measured using 2 methods: medication
      possession ratio (MPR), calculated for 365 days after the index date, and number
      of prescriptions for each index medication. Exacerbation was defined as 1 or more
      emergency department visits or hospitalizations within 1 year of the index date.
      Multivariate models were used to determine the odds of exacerbation based on
      relative compliance for each definition of compliance. RESULTS: Based on the
      median MPR, more-compliant patients were less likely to experience exacerbation
      than less-compliant patients (odds ratio, 0.94; 95% confidence interval, 0.91
      0.97; P < .001). Using the 75th percentile MPR, risk of exacerbation was even
      smaller (odds ratio, 0.89; 95% confidence interval, 0.86-0.92; P < .001). All the
      cutoff points for compliance (> or = 2 through > or = 6 prescriptions)
      demonstrated significantly less exacerbations in more-compliant vs less-compliant
      patients after adjusting for covariates. As the criteria for compliance became
      more stringent, more-compliant patients became increasingly less likely to have
      an exacerbation vs less-compliant patients. CONCLUSION: More-compliant asthmatic
      patients were significantly less likely to experience exacerbation than less
      compliant asthmatic patients. These findings demonstrate the importance of
      improving medication compliance among asthmatic patients to impact outcomes.

PMID- 17042148
TI  - Treatment with 400 microg of inhaled budesonide vs 200 microg of inhaled
      budesonide and oral montelukast in children with moderate persistent asthma:
      randomized controlled trial.
AB  - BACKGROUND: Montelukast is reported to be beneficial in asthma as add-on therapy
      to inhaled corticosteroids and may reduce the need for the latter. OBJECTIVE: To
      evaluate whether a combination of oral montelukast and 200 microg of inhaled
      budesonide has comparable efficacy to 400 microg of inhaled budesonide alone in
      children with moderate persistent asthma. METHODS: In this prospective, blinded,
      hospital-based randomized controlled trial, 71 children with moderate persistent
      asthma were randomized to receive either montelukast, 5-mg chewable tablet, with
      200 microg of inhaled budesonide or only 400 microg of inhaled budesonide daily
      for 12 weeks. Baseline and serial measurements of forced expiratory volume in 1
      second, peak expiratory flow rate, and Asthma Symptom Score were performed; the
      frequency and severity of exacerbations were also recorded. RESULTS: Measurements
      of forced expiratory volume in 1 second, peak expiratory flow rate, and Asthma
      Symptom Score showed no significant differences between the 2 groups at baseline,
      during the serial follow-up visits, and at the end of the study. However,
      children who received montelukast had a greater frequency of exacerbations vs
      those who did not (33.3% vs 9.1%; P < .01). CONCLUSION: The overall control of
      asthma with 5 mg of oral montelukast and 200 microg of inhaled budesonide is
      inferior to that with 400 microg of inhaled budesonide in children with moderate
      persistent asthma.

PMID- 17042151
TI  - Empowering patients with a history of anaphylaxis to use an epinephrine
      autoinjector without fear.

PMID- 17042150
TI  - Asthma-related health status determinants of environmental control practices for
      inner-city preschool children.
AB  - BACKGROUND: Asthma guidelines recommend environmental control practices (ECPs) to
      improve asthma health. In the inner city, where asthma morbidity is high, it is
      not known whether children's health status affects the use of ECPs. OBJECTIVE: To
      investigate health status determinants of ECPs in the homes of children with
      asthma. METHODS: Caregivers of children aged 2 to 6 years with (n = 150) and
      without (n = 150) asthma completed a survey about ECPs. Atopic status was
      determined by means of skin prick testing. RESULTS: Most ECPs were similarly
      practiced, regardless of whether the child had asthma. Only pet avoidance was
      more common in children with asthma (30% vs 19%). Asthma severity and recent
      acute health care visits for asthma were not associated with ECP use. Most ECPs
      were not linked to allergen sensitization (eg, mite and mouse), although
      cockroach-sensitized children were more likely to have cockroach control than
      nonsensitized individuals (65% vs 45%). Caregivers of asthmatic children with
      rhinitis were more likely than those without rhinitis to report ECPs, including
      pet avoidance (44% vs 15%), smoking avoidance (78% vs 53%), cockroach control
      (65% vs 42%), mouse control (78% vs 42%), air-conditioning (45% vs 24%), and
      allergyproof covers (7% vs 0%). CONCLUSIONS: The presence of asthma, asthma
      severity, and allergen sensitization seem to have little relationship to ECP use
      in the homes of inner-city children. Rhinitis was consistently linked to ECPs,
      which suggests that caregivers may make changes in the home environment for upper
      airway but not lower airway symptoms.

PMID- 17042152
TI  - Guideline 1: minimum technical requirements for performing clinical
      electroencephalography.

PMID- 17042153
TI  - Guideline two: minimum technical standards for pediatric electroencephalography.

PMID- 17042154
TI  - Guideline 3: minimum technical standards for EEG recording in suspected cerebral
      death.

PMID- 17042155
TI  - Guideline 4: standards of practice in clinical electroencephalography.

PMID- 17042156
TI  - Guideline 5: guidelines for standard electrode position nomenclature.

PMID- 17042157
TI  - Guideline 6: a proposal for standard montages to be used in clinical EEG.

PMID- 17042158
TI  - Guideline 7: guidelines for writing EEG reports.

PMID- 17042159
TI  - Guideline 8: guidelines for recording clinical EEG on digital media.

PMID- 17042160
TI  - Guideline 9A: guidelines on evoked potentials.

PMID- 17042161
TI  - Guideline 9B: guidelines on visual evoked potentials.

PMID- 17042163
TI  - Guideline 9D: guidelines on short-latency somatosensory evoked potentials.

PMID- 17042162
TI  - Guideline 9C: guidelines on short-latency auditory evoked potentials.

PMID- 17042164
TI  - Guideline 10: guidelines for writing clinical evoked potential reports.

PMID- 17042165
TI  - Immunization against periodontal disease: current strategy and future prospects.

PMID- 17042166
TI  - Association of periodontal disease severity with diabetes duration and diabetic
      complications in patients with type 1 diabetes mellitus.
AB  - OBJECTIVES: The association between periodontal disease severity and diabetes
      complications and duration in patients with type 1 diabetes mellitus (DM) was
      investigated in this comparative cross-sectional study. MATERIALS AND METHODS:
      Twenty-nine patients with type 1 DM of < or = 5 years duration were compared with
      43 patients with > 5 years duration of DM. Complete medical history and
      examination and assessments of retinopathy, neuropathy, and nephropathy were
      performed, followed by assessments of the plaque index (PI), pocket depth (PD),
      clinical attachment level (CAL), and the number of missing teeth by one examiner
      masked to the diabetic status of the patients. RESULTS: The number of missing
      teeth (4 versus 0) and CAL (2.88 vs 2.56 mm) were significantly higher in
      patients with longer DM duration (p < 0.05). For patients with > or = 5 years DM
      duration, periodontal disease severity was also greater in patients with one or
      more DM complications, as assessed by the number of missing teeth (17 vs 0; p <
      0.001) and CAL (4.74 vs 2.81 mm; p < 0.01). Stepwise multiple regression analysis
      associated the presence of > or = 1 DM complications and smoking history with
      severe attachment loss (CAL > or = 7 mm; p < 0.001). CONCLUSION: Periodontal
      disease severity is associated with both DM duration and the presence of DM
      complications in this sample of type 1 DM patients.

PMID- 17042167
TI  - SEM analyses of bacterial contamination of e-PTFE membranes and GTR clinical
      results.
AB  - The aim of the present study was to determine whether bacterial contamination of
      expanded polytetrafluoroethylene (e-PTFE) membranes and the degree of membrane
      exposure could affect the clinical results of guided tissue regeneration (GTR).
      Seven patients (aged 42 to 58 years) presented with twenty intrabony defects that
      were treated by GTR + DFDBA (decalcified freeze-dried bone allograft). Gingival
      recession, probing depths, and clinical attachment levels were recorded before
      surgery and 10 months subsequently. Exposure of the membrane was recorded at the
      moment of removal. The membranes were analyzed in three distinct regions by
      scanning electron microscopy (SEM): collar, medial and apical regions. The
      presence of host cells adhering to the e-PTFE membrane was determined and
      bacterial contamination was quantified as per Simion et al. (1994). Statistical
      analysis did not show significant differences for bacterial contamination or for
      the presence of host cells on the membrane surface at different levels of
      exposure (up to 30%, from 31% to 60%, and from 61% to 75%). Results were
      considered statistically significant at p < 0.05, according to the Kruskal-Wallis
      rank sum test. Exposure of the membrane and bacterial contamination did not
      modify the levels recorded. Bacterial contamination had an adverse effect on bone
      defect filling.

PMID- 17042168
TI  - Repeated oral hygiene instructions alone, or in combination with metronidazole
      dental gel with or without subgingival scaling in adult periodontitis patients: a
      one-year clinical study.
AB  - The aims of the present study were to evaluate the clinical efficacy of, and to
      monitor microbiologically, repeated oral hygiene instructions alone or in
      combination with metronidazole 25% gel or subgingival scaling with or without
      metronidazole gel in treatment of new, residual or recurrent periodontal pockets
      in previously treated adult periodontitis patients. Ten suitable patients were
      included in this randomized single-blind clinical study with an intra-individual
      design. Clinical parameters were measured before and at 1, 3, 6, 9 and 12 months
      after treatment. Subgingival plaque samples were taken at every examination from
      one selected site in each quadrant. Smears from plaque samples were silver
      stained and differential counting was performed under light microscopy at 1000X
      magnification. Four treatment modalities: (i) oral hygiene instruction (OHI)
      alone; (ii) OHI and metronidazole dental gel; (iii) OHI and subgingival scaling;
      (iv) OHI and subgingival scaling plus metronidazole gel, were randomly assigned
      to one quadrant of each patient. At the 12-month examination, the mean reductions
      in probing pocket depth were 2.6 mm after OHI alone, 2.8 mm after OHI and
      metronidazole gel, 3.3 mm after OHI and subgingival scaling and 2.6 mm after oral
      OHI and subgingival scaling plus metronidazole gel. The mean gains in probing
      attachment level were 2.2 mm, 1.9 mm, 2.7 mm and 1.6 mm, respectively. Although
      there were statistically significant differences in treatment responses between
      some treatment modalities at some time points, these were not considered to be
      clinically significant. Differential counts showed a shift towards a healthy
      microflora in response to all treatment modalities. From the 12-month results, it
      was concluded that the metronidazole 25% gel produced positive effects on the
      clinical parameters and on the subgingival plaque microbiological composition in
      new, residual or recurrent pockets in previously treated chronic periodontitis
      patients. However, the metronidazole gel alone or in combination with scaling
      does not seem to have any additional clinically significant therapeutic effects
      over and above those derived from improved oral hygiene resulting from monthly
      recalls, with or without subgingival scaling.

PMID- 17042169
TI  - Periodontal diseases in Asians.
AB  - Asia encompasses three of the four most populous nations in the world (China,
      India and Indonesia), accounting for nearly two-fifths of the worlds' total
      population. Over half of the world's population now inhabits Asia, which by
      definition includes countries of the Middle East and some former Socialist Soviet
      Republics. There has been a generally held view that Asians are particularly
      susceptible to periodontitis. The aim of this review is to consider the reasons
      for this view having become entrenched and to examine the evidence on which it
      could have been established and sustained. This view of a particularly high
      prevalence of periodontal diseases in Asians appears in retrospect to have
      originated from early epidemiological studies using an index system which gives
      weight to gingivitis and moderate periodontitis resulting from poor oral hygiene
      and calculus deposition, very commonly encountered in Asian populations. Studies
      that have been conducted comparing Asians immigrants with native Caucasians in
      industrialized northern hemisphere nations broadly concluded that Asians
      displayed worse periodontal conditions than Caucasians. Similarly, a classic
      study comparing Norwegian males with Sri Lankan Tamil males demonstrated worse
      periodontal conditions in the Asian males. A recent review (Albander and Rams,
      2002) has stated that those of African origin display the highest prevalence of
      periodontitis followed by Hispanics and Asians. Studies of the natural history of
      periodontal disease in Asians, of perio-dontopathogens in Asians, of risk for
      periodontal destruction, and of reasons for extraction do not appear to explain
      increased susceptibility of Asians to periodontal destruction. Poor oral hygiene
      and calculus deposits are widespread, however. Traditional assessments of
      periodontitis focus on destruction of the periodontal attachment in terms of
      attachment loss and probing pocket depths, with no consideration being given to
      the morphological features of the dentition from which the periodontal attachment
      is being lost, features that may predispose to or complicate the management of
      periodontal destruction. The Mongoloid dentition shows a high prevalence of such
      features, which adds a further dimension to the consideration of periodontal
      diseases among many Asian peoples. Appropriate strategies for the prevention and
      management of periodontal disease should focus upon improvements in the oral
      hygiene situation in the diverse continent of Asia.

PMID- 17042170
TI  - Determination of monensin, narasin, and salinomycin in mineral premixes,
      supplements, and animal feeds by liquid chromatography and post-column
      derivatization: collaborative study.
AB  - A liquid chromatographic (LC) method for the analysis of monensin, narasin, and
      salinomycin in mineral premixes, supplements, and complete animal feeds at
      medicating and trace levels was collaboratively studied. The method uses methanol
      water (90 + 10) extraction with mechanical shaking for 1 h, filtration, and
      dilution if necessary. Determination of the 3 ionophores is by reversed-phase LC
      using post-column derivatization with vanillin and detection at 520 nm. Suspect
      positive trace-level products and medicated feeds containing unexpected
      ionophores are confirmed by hexane extraction or post-column derivatization with
      dimethylaminobenzaldehyde (DMAB). Twenty-five test samples of medicated feeds,
      supplements, and mineral and drug premixes, and 9 test samples for trace-level
      analysis were sent to 11 collaborators in Bulgaria, Czech Republic, Portugal,
      France, The Netherlands, United States, and Canada. Acceptable results were
      received from 10 laboratories. For the medicated complete feeds, supplements, and
      mineral premixes, RSDr values (within-laboratory repeatability) ranged from 2.5
      to 5.2%, RSDR values (among-laboratory reproducibility) ranged from 2.7 to 6.8%,
      and HorRat values ranged from 0.31 to 1.30. For the drug premixes, the result
      variability was excessive and HorRat values ranged from 2.27 to 14.1. For the
      trace-level test samples, all laboratories correctly identified the analytes and
      did not report any false positives. RSDr values ranged from 1.3 to 9.5%, RSDR
      values ranged from 5.2 to 13.1%, and HorRat values ranged from 0.4 to 0.97.

PMID- 17042171
TI  - Ion chromatographic determination of phosphorus soluble in different extracting
      media in fertilizers.
AB  - A new method based on ion chromatography (IC) was developed for the determination
      of phosphorus in fertilizers. Fertilizers were extracted with water, mineral
      acids, and 2% formic acid, 2% citric acid, and neutral ammonium citrate solutions
      according to European Regulation No. 2003/2003 of the European Parliament and the
      Council of October 13, 2003, or the Decree of the Italian Agriculture Minister of
      June 17, 2002; the extracts were analyzed by direct injection, after simple
      filtration, by IC on an IonPac AS19 (250 x 4 mm id) column, using a KOH (21-50-21
      mM) gradient and suppressed conductivity detection. The calibration plot was
      linear over the range of 5-50 mg/L (r(2) of >0.999). The method was evaluated by
      comparison with a gravimetric method according to established norms. Associated
      uncertainty at the 95% confidence level was established as 0.47% for the
      determination of 3-46% P2O5 by IC. A good chromatographic separation of
      phosphorus forms such as phosphates and phosphites, and some other important
      anions like nitrates, chlorides, and sulfates present in many commercial
      fertilizers was also possible, with a linear response over the range of 5-50
      mg/L. After a more complete validation, this IC determination of phosphorus could
      replace more tedious methods such as those using gravimetric determinations.

PMID- 17042172
TI  - Affinity liquid chromatography method for the quantification of immunoglobulin G
      in bovine colostrum powders.
AB  - An affinity liquid chromatography (LC) method for the determination of bovine
      immunoglobulin G (IgG), using protein G coupled to an agarose support, was
      modified to permit the quantification of IgG in colostrum-based powders. Sample
      preparation included pH adjustment to 4.6 to precipitate casein and denatured
      whey protein. The method was applied to a range of colostrum powders and was
      compared with the alternative independent methods of surface plasmon resonance
      immunoassay, radial immunodiffusion, and reversed-phase LC. The method was rapid,
      and performance parameters included a working range of 10-150 microg IgG and
      precision relative standard deviation values of <10%.

PMID- 17042173
TI  - Direct determination of lycopene content in tomatoes (Lycopersicon esculentum) by
      attenuated total reflectance infrared spectroscopy and multivariate analysis.
AB  - Lycopene is a potent antioxidant that has been shown to play critical roles in
      disease prevention. Efficient assays for detection and quantification of lycopene
      are desirable as alternatives to time- and labor-intensive methods. Attenuated
      total reflectance infrared (ATR-IR) spectroscopy was used for quantification of
      lycopene in tomato varieties. Calibration models were developed by partial least
      squares regression (PLSR) using quantitative measures of lycopene concentration
      from liquid chromatography as reference method. IR spectra showed a distinct
      marker band at 957 cm(-1) for trans Carbon-Hydrogen (CH) deformation vibration of
      lycopene. PLSR models predicted the lycopene content accurately and reproducibly
      with a correlation coefficient (sigma) of 0.96 and standard error of cross
      validation <0.80 mg/100 g. ATR-IR spectroscopy allowed for rapid, simple, and
      accurate determination of lycopene in tomatoes with minimal sample preparation.
      Results suggest that the ATR-IR method is applicable for high-throughput
      quantitative analysis and screening for lycopene in tomatoes.

PMID- 17042174
TI  - Highly sensitive spectrofluorimetric determination of ephedrine hydrochloride in
      pharmaceutical preparations.
AB  - A sensitive and specific spectrofluorimetry method was developed and validated
      for the quantification of ephedrine (EP) in pharmaceutical preparations. The
      method is based on the fluorescent enhancing reaction of EP with 7-chloro-4
      nitrobenzofurazan (NBD-C1; derivatization reagent), in borate buffer of pH 9 to
      yield a yellow, fluorescent product. Under these experimental conditions, the
      derivatized product of EP had excitation and emission wavelength maxima at 458
      and 516 nm, respectively. The linear range of this method was 20-2500 ng/mL. The
      detection limit was 7.3 ng/mL EP. Intra- and interday precisions of the assay at
      3 concentrations within this range were 0.037-1.77%. The low relative standard
      deviation values indicate good precision, and high recovery values indicate
      excellent accuracy of the method. The proposed method was applied to the
      determination of the examined drugs in pharmaceutical formulations, and the
      results indicate that the method is equally as accurate, precise, and
      reproducible as the official method.

PMID- 17042175
TI  - Validation of liquid chromatography and liquid chromatography/tandem mass
      spectrometry methods for the determination of etoricoxib in pharmaceutical
      formulations.
AB  - Reversed-phase liquid chromatography (LC) and LC/tandem mass spectrometry
      (LC/MS/MS) methods were developed and validated for the determination of
      etoricoxib in pharmaceutical dosage forms. The LC method was performed by
      reversed-phase chromatography on a Synergi fusion C18 column (150 x 4.6 mm id)
      maintained at ambient temperature. The mobile phase consisted of 0.01 M
      phosphoric acid, pH 3.0-acetonitrile (62 + 38, v/v) at a flow rate of 1.0 mL/min,
      and photodiode array detection at 234 nm was used. The chromatographic separation
      was obtained within 7.0 min, and calibration curves were linear in the
      concentration range of 0.02-150 microg/mL. The LC/MS/MS method was performed on a
      Luna C18 column (50 x 3.0 mm id). The mobile phase consisted of acetonitrile
      water (95 + 5)-0.1% acetic acid (90 + 10, v/v). Detection was performed by
      positive electrospray ionization in the multiple reaction monitoring mode,
      monitoring the transitions 359.3 > 280.0 and 332.0 > 95.0 for etoricoxib and
      piroxicam (internal standard), respectively. The chromatographic separation was
      obtained within 2.0 min, and calibration curves were linear in the concentration
      range of 1-5000 ng/mL. Validation parameters, such as specificity, linearity,
      precision, accuracy, and robustness, were evaluated, which gave results within
      the acceptable range for both methods. Moreover, the proposed methods were
      successfully applied for routine quality control analysis of pharmaceutical
      products and showed significant correlation (r = 0.9999) of the results.

PMID- 17042176
TI  - A validated spectrofluorometric assay for the determination of certain macrolide
      antibiotics in pharmaceutical formulations and spiked biological fluids.
AB  - This paper describes a simple spectrofluorometric method for the analysis of 4
      macrolide antibiotics. The method is based on the condensation of 10% (w/v)
      malonic acid and acetic acid anhydride under the catalytic effect of tertiary
      amine groups of the studied macrolides. The relative fluorescence intensity of
      the condensation product was measured at 397/452 nm (excitation/emission) for
      azithromycin dihydrate and at 392/445 nm (for clarithromycin, erythromycin
      ethylsuccinate, and roxithromycin. All variables affecting the reaction
      conditions were studied. The effects of potential interference due to common
      excipients, such as starch, lactose, sucrose, glucose, gum acacia, and magnesium
      stearate, as well as trimethoprim and sulfisoxazole acetyl formulated in
      primomycin capsules and pediazole oral suspension, respectively, were studied. A
      validation study for the proposed method was carried out according to U.S.
      Pharmacopeia 2002. The linearity ranges were 3-80 ng/mL for all of the cited
      macrolides. The limit of detection range was 0.74-1.20 ng/mL, while the limit of
      quantitation range was 2.47-4.02 ng/mL. The method was applied for the assay of
      the studied macrolides in pure pharmaceutical formulations and in spiked
      biological fluids. Results were compared with those obtained from the reported
      method, where calculated t- and F-values indicated high accuracy and good
      precision for the proposed method.

PMID- 17042177
TI  - Spectrofluorometric determination of citalopram in pharmaceutical preparations
      and spiked human plasma using organized media.
AB  - The native fluorescence of citalopram (CIT) was obtained in citrate buffer of pH
      6.5 with and without beta-cyclodextrin (beta-CD) or sodium dodecyl sulfate (SDS)
      as fluorescence enhancers at 305 nm using 242 nm for excitation. Micellar systems
      of ionic and nonionic surfactants were investigated by measuring the fluorescence
      intensity of the analyte-surfactant system. In slightly acidic aqueous solution
      of pH 6.5, CIT was better incorporated in CDs and SDS micelles. The luminescence
      emission from CIT was found to be greatly enhanced by SDS micelles. The
      fluorescence intensity enhancements in CDs medium and in SDS as ionic surfactant
      relative to slightly acidic aqueous solution were 125 and 250%, respectively.
      Organized media-enhanced spectroflourometric methods were developed for the
      determination of CIT, in pure form as well as in pharmaceutical preparations. The
      fluorescence intensity-concentration plots were rectilinear over the ranges 0.06
      to 0.64, 0.04 to 0.40, and 0.02 to 0.26 microg/mL with lower detection limits of
      0.02, 0.01, and 0.007 microg/mL, either in citrate buffer only or in beta-CD and
      SDS as organized media, respectively. Furthermore, the high sensitivity attained
      by using SDS as organized medium allowed in vitro spectrofluorometric
      determination of CIT in spiked human plasma. Interference from endogenous amino
      acids has been overcome by using the solid-phase extraction technique; the mean
      recovery (n = 5) was 100.1+/-0.8%

PMID- 17042178
TI  - First-derivative spectrophotometry in the analysis of rosiglitazone in coated
      tablets.
AB  - First-derivative spectrophotometry, applying the peak-zero method, was developed
      for the determination of rosiglitazone (RSG) in coated tablets. The solutions of
      standard and sample were prepared in ethanol. Quantitative determination of the
      drug was performed at 331.4 nm (N = 4; delta lambda = 3.2 nm) and was evaluated
      for the parameters specificity, linearity, precision, and accuracy. The
      specificity test showed that there was no interference from excipients commonly
      found in the commercial pharmaceutical formulation at 331.4 nm. The standard
      curve showed a correlation coefficient of 0.9997. Precision was demonstrated by a
      relative standard deviation value of 0.50%. The recovery test resulted in an
      average of 100.06%, which confirmed the accuracy of the method. The results for
      first-derivative spectrophotometry (D(1)), liquid chromatography, and micellar
      electrokinetic chromatography were compared by analysis of variance (ANOVA), and
      there were no significant differences among these methods. Therefore, D(1) can be
      easily and directly applied to analyze RSG in coated tablets.

PMID- 17042179
TI  - Proficiency testing as a tool to assess the performance of visual TLC
      quantitation estimates.
AB  - The use of rapid and inexpensive nonlaboratory-based screening tests for drug
      quality assessments is recommended as a component of a drug quality assurance
      program in poor resource settings. We have established routine Minilab test
      procedures to screen product quality and a proficiency testing program to
      determine the competency of the inspectors and reliability of results. Samples
      for the proficiency testing were prepared by pulverizing a standard reference
      tablet of the appropriate drug and making serial dilutions with starch to obtain
      concentrations of 0, 40, and 100%. The samples, which were labeled only with the
      drug name and an identifying letter, were given to inspectors for quality
      screening using Minilab procedures. In round 1 of the proficiency test, only 3 of
      28 substandard samples were correctly identified. Round 2 of the proficiency
      test, which was administered after a performance qualification test for the
      analytical method, showed much improvement: 19 of 27 substandard drugs were
      correctly identified, while 5 out of 9 inspectors made the correct inference on
      the quality of 45 samples. However, in both rounds, 2 inspectors failed to
      identify substandard samples, indicating that their technical competencies need
      to be improved for the reliability of the results. Although the thin-layer
      chromatography screening methods provide a rapid means for drug quality
      assessment, they need to be put in the hands of competent users. The inclusion of
      a proficiency test in the screening program provides a measure of determining
      competency of the personnel and reliability of the results.

PMID- 17042180
TI  - Determination of lomefloxacin in tablet preparations by liquid chromatography.
AB  - A sensitive, precise, and specific high-performance liquid chromatography (HPLC)
      method was developed for the assay of lomefloxacin (LFLX) in raw material and
      tablet preparations. The method validation parameters yielded good results and
      included the range, linearity, precision, accuracy, specificity, and recovery. It
      was also found that the excipients in the commercial tablet preparation did not
      interfere with the assay. The HPLC separation was performed on a reversed-phase
      Phenomenex C18 column (150 x 4.6 mm id, 5 microm particle size) with a mobile
      phase composed of 1% acetic acid-acetonitrile-methanol (70 + 15 + 15, v/v/v),
      pumped isocratically at a flow rate of 1.0 mL/min. The effluent was monitored at
      280 nm. The calibration graph for LFLX was linear from 2.0 to 7.0 mg/mL. The
      interday and intraday precisions (relative standard deviation) were less than
      1.0%. The method was applied for the quality control of commercial LFLX tablets
      to quantitate the drug.

PMID- 17042181
TI  - Evaluation of the International Organization for Standardization-International
      Dairy Federation (ISO-IDF) draft standard method for detection of Enterobacter
      sakazakii in powdered infant food formulas.
AB  - As a result of the growing recognition of Enterobacter sakazakii as an emergent
      pathogen, the International Dairy Federation (IDF) and the International
      Organization for Standardization (ISO) have standardized a reference method for
      the detection of E. sakazakii in milk powder products and powdered infant food
      formulas (IFF). The objectives of this study were to assess the applicability of
      the ISO-IDF draft standard, and to compare several chromogenic selective media
      for E. sakazakii [ready-to-use ESIATM, homemade E. sakazakii isolation agar, and
      Druggan-Forsythe-lversen (DFI) agar], and a selective media for
      Enterobacteriaceae Violet Red Bile Glucose (VRBG). We found that the method is
      sensitive, selective, and applicable to the analysis of powdered IFF, provided
      that some modifications are added. In particular, definition of typical colonies
      on chromogenic media should be less restrictive, and the possibility of using
      chromogenic media other than ESIA should be introduced. Any of the chromogenic
      media tested here could be used initially, since their performances were similar.
      In these media, alpha-glucosidase-positive but non-yellow-pigmented isolates
      should be also considered. Consequently, the yellow pigmentation test should be
      abandoned, or completed with another test in order to select colonies to confirm.
      Although the specificity of VRBG was relatively poor, it could be used as a
      second nonchromogenic medium.

PMID- 17042182
TI  - Two rapid methods for detection of Escherichia coli exceeding 10(4)/g action
      levels: precollaborative study.
AB  - The current AOAC Method 966.24 for enumeration of Escherichia coli in foods uses
      a most probable number (MPN) procedure with extensive confirmation steps. Two new
      methods based on membrane filtration (MF) were compared to the MPN reference
      method for detection of high levels of E. coli in 5 food types, some of which
      represent categories for which the U.S. Food and Drug Administration (FDA)
      mandates additional testing if an action level of 10(4)/g E. coli is exceeded.
      Ground beef, which is not FDA regulated, was also tested. The 5 food types were
      all inoculated at 3 levels: 10(2)/g, > or = 10(4)/g, and > or = 10(5)/g E. coli.
      An MF protocol using either m-ColiBlue24 (CB) or lauryl sulfate tryptose plus
      BCIG (LST/BCIG) was an effective potential alternative to the reference method.
      Sensitivity and specificity for both CB and LST/BCIG were 98 and 100%,
      respectively. Agreement between MPN and both CB and LST/BCIG was 98%. The 2
      proposed methods allow completion of both presumptive and confirmatory steps in 1
      3 days, whereas the reference method requires as many as 11 days. Exclusivity
      testing with 50 non-E. coli strains indicated 100% were correctly ruled out by
      the proposed protocols. Inclusivity testing was used to determine whether typical
      results were obtained after incubation of E. coli cultures on CB or LST/BCIG for
      24 h. Of 50 E. coli strains tested, 100% yielded typical results after incubation
      on CB, and 98% yielded typical results after incubation on LST/BCIG.

PMID- 17042184
TI  - Collaborative trial for validation of a real-time reverse transcriptase
      polymerase chain reaction assay for detection of central nervous system tissues
      as bovine spongiform encephalopathy risk material: part 1.
AB  - A collaborative trial was conducted to evaluate a real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) assay for detection of central nervous system
      (CNS) tissues in meat products (e.g., sausages). The method is based on the
      detection of ruminant glial fibrillary acidic protein (GFAP) mRNA by applying
      real-time RT-PCR. The assay was evaluated through a multicenter trial involving
      12 participating laboratories that received coded cDNA obtained from 3 different
      types of sausages. The participants used 5 different real-time detection systems.
      The results obtained in this validation revealed that this real-time RT-PCR assay
      performed well in the different laboratories with a detection limit of at least
      0.1% CNS in those test materials that contained strongly heat-treated samples
      (sausages cooked at 120 degrees C) and the medium heat-treated samples (sausages
      cooked at 80 degrees C). The detection limit of liver sausages was determined to
      be 0.2% of CNS. Neither the samples with no CNS additive nor the bovine DNA and
      the negative control containing 100% swine brain gave any positive signals. The
      presented results indicate that the real-time RT-PCR assay was just as
      reproducible between laboratories, as repeatable within a laboratory, could
      reliably be used for detection of bovine spongiform encephalopathy risk material
      in meat and meat products, and signify that it may be used with confidence in any
      laboratory.

PMID- 17042183
TI  - Interlaboratory study of the Charm ROSA Safe Level Aflatoxin M1 Quantitative
      lateral flow test for raw bovine milk.
AB  - An interlaboratory study of 21 public health, state agriculture, and industry
      laboratories in the United States tested raw commingled bovine milk containing
      aflatoxin M1 using the Charm Rapid One Step Assay (ROSA) Safe Level Aflatoxin M1
      Quantitative lateral flow method. Blind coded sample pairs were fortified with 0,
      300, 350, 400, 450, 500, and 550 parts per trillion (ppt) aflatoxin M1. A ROSA
      reader quantitatively interpreted test strips with ppt readings. Readings < or =
      400 ppt were interpreted as negative, and readings >400 ppt were interpreted as
      positive. Initial positive samples were subsequently assayed 2 additional times.
      If both retest results were >400 ppt, the sample was called positive/ actionable
      relative to U.S. and Codex levels, 500 ppt. The concentration of 400 ppt was
      chosen for the positive/negative interpretation to provide 90% sensitivity with
      95% confidence at the 500 ppt legislative level. The combined false negative rate
      was <5% (4 of 83) for samples at 500 and 550 ppt. The false violatives at 0, 300,
      350, 400, and 450 ppt (n = 42 at each level) were 0, 0, 21, 14, and 93%,
      respectively. The 90% positive concentration with 95% confidence was 503 ppt by
      probit analysis. The average intralaboratory repeatability was 11% and average
      interlaboratory reproducibility was 13% for the fortified sample pairs. High
      performance liquid chromatography analysis of the study samples by 5 laboratories
      showed 38% false negatives with the 500 and 550 ppt samples, and a 0% false
      violative rate with samples less than the 500 ppt action level.

PMID- 17042185
TI  - Determination of the acid value of instant noodles: interlaboratory study.
AB  - An interlaboratory study was performed to evaluate the method for determining the
      acid value of instant noodles, based on the Japanese Agricultural Standard (JAS),
      with extraction of lipid using petroleum ether at a volume of 100 mL to the test
      portion of 25 g. Thirteen laboratories participated and analyzed 5 test samples
      as blind duplicates. Statistical treatment revealed that the repeatability (RSDr)
      of acid value was <6.5%, and the reproducibility (RSDR) of acid value was <9.6%.
      The HorRat values (RSDR/predicted RSDR) were 1.2-1.8, where the RSDR and the
      predicted RSDR were obtained in terms of free fatty acids in the noodles per unit
      weight, using the equation [acid value = percent free fatty acids (as oleic) x
      1.99] and the extracted lipid contents. This method was shown to have acceptable
      precision by the present study.

PMID- 17042186
TI  - Interlaboratory transfer of a real-time polymerase chain reaction assay for
      quantitative detection of genetically modified maize event TC-1507.
AB  - A real-time polymerase chain reaction (QPCR) assay was developed for quantitative
      detection of a genetically modified (GM) maize event TC-1507 and modification to
      conventional PCR for qualitative purposes. Sequences 5'-flanking TC-1507 full
      length insert were characterized and showed multiple rearrangements involving
      insert and maize chloroplast fragments. The event specificity of the TC-1507
      assays was based on the detection of transgene and plant rearranged sequences
      found to 5' flank the insertion site. They were fully specific and exhibited a
      limit of detection below 10 target copies, allowing consistent detection of 0.1%
      GM levels. The QPCR was highly linear and efficient and proved adequate for
      quantification of GM contents, aiming at the fulfillment of legal requirements
      established in the European Union (i.e., compulsory labeling of TC-1507 levels
      >0.9%). It satisfactorily determined TC-1507 contents on different matrixes and
      was successfully transferred a different laboratory.

PMID- 17042187
TI  - Determination of protein in milk powder using 2-sulfophenylazo-rhodanine as a
      probe by the enhanced resonance Rayleigh light-scattering technique.
AB  - In this paper, the interaction between 2-sulfophenylazo-rhodanine and protein was
      investigated by Rayleigh light-scattering technique. Based on this, a novel
      method for the determination of protein was developed. The effects of different
      conditions, such as acidity and media, were investigated thoroughly, and the
      optimum conditions were confirmed. Bis(2-ethylhexyl)sulfosuccinate (AOT)
      microemulsion, which is introduced into the protein determination, markedly
      increased the sensitivity of the system by changing the microenvironment. In pH
      2.80 Britton-Robinson buffer solution in the presence of AOT microemulsion, the
      detection limits of bovine serum albumin, human serum albumin, ovalbumin, and
      gamma-globulin are 5.4, 4.5, 9.8, and 10.1 ng/mL, respectively. The method
      developed in this paper has been applied to the determination of protein in milk
      powder with satisfactory results.

PMID- 17042188
TI  - Quantitation of Indian krait (Bungarus caeruleus) venom in human specimens of
      forensic origin by indirect competitive inhibition enzyme-linked immunosorbent
      assay.
AB  - An indirect competitive inhibition enzyme-linked immunosorbent assay was reported
      to detect krait venom in human specimens of forensic origin. Polyclonal anti
      krait venom antibodies were characterized by indirect antibody capture assay. The
      calibration plot was constructed based on linear regression analysis (y = 72.85 -
      12.29x, r(2) = 0.98) with concentration ranges from 0.013 to 1000 ng/well of
      krait venom with a limit of detection of 0.2 ng/mL in the assay system. The IC50
      (inhibitory concentration at 50% displacement) value of krait venom was observed
      to be 70 ng. Spiking studies indicated recoveries of 95-100% and 94-100% when
      various concentrations of krait venom were spiked to rat tissues (skin, liver,
      and kidneys) and pooled human serum, respectively. Polyclonal anti-krait venom
      antibodies showed no cross-reactivity with cobra and viper venom when tested in
      the assay system. The coefficient of variation of various concentrations of
      working range in intra-assay (n = 6) was <5%, whereas in interassay (n = 6) it
      was observed to be < or 7%. Further, the method was used to quantitate krait
      venom in human autopsy and biopsy specimens of forensic origin. Concentration of
      krait venom was found to be in the range of 4-172 ng/100 mg skin or skin
      scrapings and 64-378 ng/mL blood or serum. The methodology may find application
      in forensic laboratories to assess the cause of death in the cases of krait-bite
      victims.

PMID- 17042189
TI  - Development and in-house validation of a microbiological assay for determination
      of cefepime in injectable preparations.
AB  - Cefepime is a new parenteral cephalosporin that has been described as a fourth
      generation, broad-spectrum antibiotic. This paper reports the development and in
      house validation of an agar diffusion bioassay using a cylinder-plate method for
      the determination of cefepime in powder for injection. The validation performed
      yielded good results in terms of linearity, precision, accuracy, and robustness.
      The assay is based on the inhibitory effect of cefepime upon the strain of
      Micrococcus luteus ATCC 10240 used as the test microorganism. The results of
      assays were treated statistically by analysis of variance (ANOVA) and were found
      to be linear (r = 0.99993) in the selected range of 8.0-32.0 microg/mL; precise
      [repeatability: relative standard deviation (RSD) = 1.39%, intermediate
      precision: between-day RSD = 1.77%, and between-analyst RSD = 1.97%] and
      accurate. Comparison of bioassay and liquid chromatography by ANOVA showed no
      significant difference between methodologies. The results demonstrated the
      validity of the proposed bioassay, which is a simple and useful alternative
      methodology for cefepime determination in routine quality control.

PMID- 17042190
TI  - Modification to the AOAC Sporicidal Activity of Disinfectants Test (Method
      966.04): collaborative study.
AB  - In an effort to improve AOAC Method 966.04, the Sporicidal Activity of
      Disinfectants Test, selected modifications to the procedure were evaluated in a
      collaborative study. Method 966.04 is used to generate efficacy data to support
      the product registration of sporicides and sterilants. The method is a carrier
      based test that provides a qualitative measure of product efficacy against spores
      of Bacillus subtilis and Clostridium sporogenes. The use of garden soil extract
      and the lack of standard procedures for the enumeration of spores and
      neutralization of the test chemicals have been considered problematic for many
      years. The proposed modifications were limited to the B. subtilis and hard
      surface carrier (porcelain penicylinder) components of the method. The study
      included the evaluation of a replacement for soil extract nutrient broth and an
      establishment of a minimum spore titer per carrier, both considered crucial for
      the improvement and utilization of the method. Additionally, an alternative hard
      surface material and a neutralization confirmation procedure were evaluated. To
      determine the equivalence of the proposed alternatives to the standard method, 3
      medium/carrier combinations, (1) soil extract nutrient broth/porcelain carrier
      (current method), (2) nutrient agar amended with 5 microg/mL manganese
      sulfate/porcelain carrier, and (3) nutrient agar amended with 5 microg/mL
      manganese sulfate/stainless steel carrier were analyzed for carrier counts, HCI
      resistance, efficacy, quantitative efficacy, and spore wash-off. The test
      chemicals used in the study represent 3 chemical classes and are commercially
      available antimicrobial liquid products: sodium hypochlorite (bleach),
      glutaraldehyde, and a combination of peracetic acid and hydrogen peroxide. Four
      laboratories participated in the study. The results of the spore titer per
      carrier, HCI resistance, efficacy, and wash-off studies demonstrate that amended
      nutrient agar in conjunction with the porcelain is comparable to the current
      method, soil extract nutrient broth/porcelain. The nutrient agar method is
      simple, inexpensive, reproducible, and provides an ample supply of high quality
      spores. Due to the current use of porcelain carriers for testing C. sporogenes,
      it is advisable to retain the use of porcelain carriers until stainless steel can
      be evaluated as a replacement carrier material for Clostridium. The evaluation of
      stainless steel for Clostridium has been initiated by the Study Director. Study
      Director recommendations for First Action revisions are provided in a modified
      method.

PMID- 17042192
TI  - Determination of benzimidazole fungicides in soil samples using microwave
      assisted micellar extraction and liquid chromatography with fluorescence
      detection.
AB  - A simple and fast analytical method was developed for the determination of
      benzimidazole fungicides (benomyl, carbendazim, thiabendazole, and fuberidazole)
      in soil samples. The analytes were extracted from the soil samples by means of
      conventional microwave-assisted extraction, using the non-ionic surfactants
      polyoxyethylene 10 lauryl ether (POLE) and oligoethylene glycol monooalkyl ether
      (Genapol X-080) as extractants. Determinations were made by using liquid
      chromatography with direct fluorescence detection. The use of an analytical
      column Symmetry C-18 offered short retention times of analytes without the need
      of any pH regulators with mobile phase methanol-water (50 + 50, v/v). The best
      results were obtained using 5% (v/v) POLE as extractant with recoveries of the
      fungicides in spiked soil samples between 71 and 105%. The results were compared
      with those obtained when Soxhlet extraction was applied to the same soil samples.

PMID- 17042191
TI  - Microbiological assay for the determination of telithromycin in tablets.
AB  - This study describes the development and validation of a microbiological assay,
      applying the cylinder-plate method, for the determination of the antibiotic
      telithromycin. The microbiological method consisted of a cylinder-plate agar
      diffusion assay using Micrococcus luteus ATCC 9341 as the test microorganism. The
      response graphs for standard and sample solutions were linear (r = 0.9987), and
      no parallelism deviations were detected in the tested concentrations (0.25, 0.5,
      and 1.0 microg/mL). The interday precision was 2.67%. Recovery values were
      between 96.75 and 100.91%. A preliminary stability study of telithromycin showed
      that the microbiological assay is specific for the determination of telithromycin
      in the presence of its degradation products. The proposed method allows the
      quantitation of telithromycin in pharmaceutical dosage form and can be used for
      drug analysis in routine quality control.

PMID- 17042193
TI  - Effect of ultrasound agitation on the release of heavy elements in Certified
      Reference Material of human hair (CRM BCR 397).
AB  - An ultrasonic-assisted leaching procedure was developed for the determination of
      heavy elements (As, Cu, Cd, Pb, and Zn) in Certified Reference Material of human
      hair (CRM 397) provided from the Community Bureau of Reference (BCR) of the
      Commission of the European Community. Concentrated nitric acid-30% hydrogen
      peroxide (2 + 1) was used for the leaching method. The effects of different
      factors on acid leaching of elements, such as presonication time (without
      ultrasonic stirring), sonication or exposure time to ultrasound, and temperature
      of the ultrasonic bath have been investigated. Optimum values of these parameters
      were selected for the maximum extraction of heavy metals from CRM BCR 397 and
      human scalp hair samples of normal healthy males. To check the validity of the
      proposed method, a wet acid digestion method was used to obtain the total
      elemental concentration in CRM BCR 397 and scalp hair samples. Cu and Zn in
      leachate and digests were measured by flame atomic absorption spectrometry using
      a conventional air/acetylene flame, while As, Cd, and Pd were determined by
      electrothermal atomic absorption spectrometry. Under optimized conditions, the
      recovery for Zn, Cd, Pd, As, and Cu was 98, 98.5, 97.5, 98.2, and 95%,
      respectively, of those obtained with the wet acid digestion method.

PMID- 17042194
TI  - Single-laboratory validation of a method for the determination of furan in foods
      by using static headspace sampling and gas chromatography/mass spectrometry.
AB  - A headspace gas chromatography/mass spectrometry method was developed and
      validated in-house for the determination of furan in foods. The method of
      standard additions with d4-furan as the internal standard was used to quantitate
      furan. The limit of detection and limit of quantitation (LOQ) values ranged from
      0.2 and 0.6 nglg, respectively, in apple juice to 0.9 and 2.9 ng/g, respectively,
      in peanut butter. Recoveries were obtained at 0.5, 1, 2, and 3 times the LOQ. At
      1, 2, and 3 times the LOQ, the recoveries ranged from 89.4 to 108%, and the
      relative standard deviations ranged from 3.3 to 17.3% for all the matrixes. For
      apple juice, chicken broth, and infant formula, the averaged coefficients of
      determination from the linear regression analyses were >0.99 with each food
      fortified at 0.5, 1, 2, and 3 times the LOQ. The coefficients of determination
      were >0.99 for green beans and 0.96 for peanut butter with the foods fortified at
      1, 2, and 3 times the LOQ. Within-laboratory precision was determined by
      comparing the amounts of furan found in 18 samples by 2 analysts on different
      days with different instruments. For most of the foods, the difference between
      the amounts found by each analyst was <18%. The method was used to conduct a
      survey of >300 foods. The furan levels found ranged from none detected to 174
      ng/g.

PMID- 17042195
TI  - Determination of eight synthetic pyrethroids in bovine fat by gas chromatography
      with electron capture detection.
AB  - Synthetic pyrethroids are among the most widely used classes of insecticides, and
      their uses are varied, including plant protection, animal dips, and as a
      treatment for human clothing and bedding in very hot climates. Veterinary
      applications include ear tags, pour-on formulations, sprays, and dips. Persistent
      residues have been reported in livestock, and routine monitoring programs in
      other countries have found detectable residues of various pyrethroids in fat. A
      method has been developed using solid-phase extraction that reduces the
      quantities of solvents used, the time required, and the amount of glassware used
      compared to an earlier method on which it was based. The scope of analytes tested
      included the 5 compounds cited in the earlier method (flucythrinate, permethrin,
      cypermethrin, fenvalerate, and deltamethrin) and, in addition, cyfluthrin, lambda
      cyhalothrin, and fluvalinate. Sample extracts were analyzed by gas chromatography
      with electron capture detection using selected chromatographic peaks
      characteristic of each compound. Limits of quantification for the compounds were
      from 25-50 microg/kg, with a linear response for all compounds to 200 microg/kg.
      Recoveries ranged from 80 to 123%.

PMID- 17042196
TI  - Determination of chloramphenicol in royal jelly by liquid chromatography/tandem
      mass spectrometry.
AB  - A liquid chromatographic/tandem mass spectrometric method was developed and
      validated for the determination of chloramphenicol (CAP) in royal jelly. Royal
      jelly samples were first denatured with lead acetate solution, and the CAP was
      extracted with solid-phase extraction before separation by liquid chromatography.
      A triple-quadrupole mass spectrometer operated in the negative electrospray
      ionization and selected-reaction monitoring mode was used for the detection of
      CAP. For method validation, royal jelly samples were fortified at CAP levels
      between 0.1 and 10.0 microg/kg; at these levels, recovery values (internal
      standard-corrected) ranged from 93.3 to 105.0%, and the within-laboratory
      reproducibility (relative standard deviation) was < or = 9.1%. The decision limit
      was 0.07 microg/kg, and the detection capability was 0.1 microg/kg.

PMID- 17042197
TI  - Simultaneous determination of florfenicol and florfenicol amine in fish, shrimp,
      and swine muscle by gas chromatography with a microcell electron capture
      detector.
AB  - A rapid and sensitive gas chromatography method was developed for the
      simultaneous determination of florfenicol (FF) and its metabolite florfenicol
      amine (FFA) in fish, shrimp, and swine muscle. The extracted samples were
      defatted with hexane and cleaned up by solid-phase extraction using Oasis MCX
      cartridges. The eluate was evaporated to dryness, and residues were derivatized
      and determined by gas chromatography with a microcell electron capture detector.
      Overall average recoveries ranged from 81.7 to 109.7% for fish, 94.1 to 103.4%
      for shrimp, and 71.5 to 91.4% for swine muscle. The detection limit was 0.5 ng/g
      for FF and 1 ng/g for FFA, respectively. The method was validated for the
      determination of incurred swine muscle samples in an actual residue study.

PMID- 17042198
TI  - Patient's page. Oral health care for older patients.

PMID- 17042199
TI  - The dental profession's relationship with third party carriers. 1976.

PMID- 17042200
TI  - Muskogee's first dentist was talented singer as well.

PMID- 17042201
TI  - Five questions dentists should ask about their money.

PMID- 17042202
TI  - The Health Professional Program (HPP).

PMID- 17042204
TI  - [Non surgical management of ectopic pregnancy].
AB  - During the past 25 years, the incidence of ectopic pregnancy has progressively
      increased while the morbidity and mortality have substantialy decreased, and the
      treatment has progressed from salpingectomy by laparotomy to conservative surgery
      by laparoscopy and more recently to medical therapy with Methotrexate or
      expectant management. This therapeutic transition from surgical emergency to non
      surgical managment has been attributed to early diagnosis through the use of
      sensitive assays for hCG and the high definition of vaginal ultrasound. By using
      these sensitive diagnostic tools, we are now able to select those patients who
      are most likely to respond to expectant or medical managment versus those who are
      at high risk of rupture and require surgery. We have reviewed the scientific
      literature on ectopic pregnancy published over the past 20 years, with the aim to
      assess the value of non surgical managment of etopic pregnancy. Predictor factors
      of expectant managment are discussed. Medical therapy with methotrexate: results,
      indications, Unpleasant side effects and complications are detailed. Several
      protocols are defined and therapeutic supervision is etablished. The authors
      offred several recommandations for OB/GY wich will optimize the effectivness of
      non invasive methods for treatment of ectopic pregnancy.

PMID- 17042205
TI  - [Prospective study of 420 biopsies realised in patients with duodenal ulcer with
      positive Helicobacter pylori].
AB  - It's a prospective study leaded between September 1997 and july 1999 (23 months )
      in 75 patients with duodenal ulcer and positif for Helicobacter pylori. All
      patients had a first endoscopy with antral, fundic and duodenal biopsies,
      followed one month later by a second control fibroscopy with biopsies of the same
      sites. A total of 420 biopsies was realised. Chronic gastritis was evaluated
      according to sydney system. Patients was divided by randomisation in 4 groups.
      Every group was received a different therapeutic association. The results was
      conform to liberation concering activity 80%, intestinal metaplasia 12%.
      inflammation 100%. Atrophy was observed in 56% of cases, this percentage is
      variable in literature; chronic gastritis was predominant in antre relatively to
      fundus (p<0.005). After treatment, a significative fall of Helicobacter pylori
      and activity and atrophy was established, contrarity to intestinal metaplasia and
      chronic inflammation witch are persisted. The prevalence of follicular gastritis
      was 57%. The better rate of ulcer cicatrisation and Helicobacter pylori
      eradication was respectively of 79% and 66% in group 1 treated by omeprazol,
      amoxcillin, metronidazol by comparison with the others 3 groups (p<0.005).

PMID- 17042206
TI  - [Return to work after acute myocardial infarction].
AB  - OBJECTIVES: The aim of this work was to study the professional repercussions of
      acute myocardial infarction and to analysis medical, social and occupational
      factors which could influence return to work. MATERIAL AND METHODS: Our study
      concerns 70 patients less than 66 years old, working before their hospitalization
      and having been admitted for acute myocardial infarction between January 1-st,
      1999 and December 31, 2000 in the Department of Cardiac Resuscitation of hospital
      La Rabta of Tunis. Data were collected from retrospective review of folders and
      answers to a questionnaire for which the patients have been summoned in 2002.
      RESULTS: There were 70 patients almost exclusively men (n=69). The mean age was
      49.0 +/- 6.8 years. The mean follow-up was 27.2 +/- 7.7 months. Sixty one
      patients (87.1%) have initially been back to work and eight of them lost it
      secondarily. The average delay of return to work has been 91+/- 111 days. The
      direct repercussions of myocardial infarction on the professional capacities was
      observed at the majority of patients. CONCLUSION: Despite an important
      professional repercussions of acute myocardial infarction, our study showed a
      high rate of return to work with relatively short delays.

PMID- 17042207
TI  - [Ovary teratoma. Report of 91 cases].
AB  - OBJECTIVE: To analyse the clinical and anatomic aspects of cystic teratomas of
      the ovary, caracteristics of patients having cystic teratomas and the management
      trends at our institution. STUDY DESIGN: Retrospective study of 91 cases of
      cystic teratomas of the ovary diagnosed and treated at Farhat -Hached Hospital
      (Sousse) between 1 january 1995 and 30 june 2003. RESULTS: Cystic teratomas
      constituted 12.13% of all ovarian tumors diagnosed and treated at our institution
      during the study period. The median of age was 33.35 ans. Abdominal or pelvic
      pain was the most frequent symptom for presentation in 67% of the cases. In
      addition; incidental finding was noted in 25.3% of the cases and swelling in 23%
      of the cases. The mean tumor diameter was 10 cm. The rate of bilateral cystic
      teratomas of the ovary was 14.3%. 19.8% of cystic teratomas has occurred in
      pregnancy. The operative video-laparoscopy was employed in 9 cases, laparotomy
      was employed in82 cases. Histopathological evaluation has detected 96.7% cases of
      mature teratomas, and 3.3% cases of immature teratomas. CONCLUSION: Cystic
      tertomas are the most common ovarian neoplasms, that occurs most commonly during
      the reproductive years. The operative laparoscopy is the most common modality of
      treatment of mature cystic teratomas. Immature teratomas must be treated by
      laparotomy associated if necessary to chimiothrapiy.

PMID- 17042208
TI  - [Lobular idiopathic granulomatos mastitis. About 10 cases].
AB  - Our retrospective study was performed on 10 cases of granulomatous mastitis
      registered in Obstetric Gynaecology Department and Pathology Department of CHU F.
      Hached, Sousse, during 8 years period. The mean age was 36.4 years (range 32-59).
      Among these 10 cases. 8 were observed in reproductive-age women and 2 were noted
      in menopausal women. Clinical findings showed unilateral breast nodule associated
      with inflammatory signs in 4 cases, mammelonary retraction in 2 cases and serous
      or sero-purulent mamelonnary flow in 4 cases. Mamnmographic examination suggested
      a malignant tumor in 5 patients. In all cases, the diagnosis is made by
      histopathology. Surgical treatment consisted in wide excision with drainage or
      radical mastectomy, eventually with combination with antibiotic therapy and non
      steroid anti-inflammatory drugs. Prognostic features showed a good cicatrization
      in 4 cases, local recurrence and cutaneous fistulization in one patient.
      Granulomatous mastitis aetiology is still unclear, auto-immune aetio-pathogenesis
      appears more interesting and should be clarified.

PMID- 17042209
TI  - [Cor triatriatum: of six operated patients report].
AB  - Six cases of cortriatriatum operated between January 1990 and April 2004. Their
      ages ranged from 3 months to 22 years. Associated lesions are present in 4
      patients. They consisted mostly of interatrial defects. The echocardiography has
      been considered the procedure of choice for the diagnosis. Results of surgery
      were excellent for all patients with a mean follow up of 5 years.

PMID- 17042210
TI  - [Cardiac involvement in Emery-Dreifuss muscular dystrophy: a case report].
AB  - Emery Dreifuss muscular dystrophy (EDMD) is an uncommon hereditary myopathy
      characterized by 3 symptoms: slow progressive muscular atrophy, muscular
      contractures and cardiac disease which affect prognosis. We report a 22 year-old
      patient with EDMD which shows the typical features of the associated dilated
      cardiomyopathy, ventricular arrhythmia, atrio-ventricular block, atrial
      standstill then atrial paralysis.

PMID- 17042211
TI  - [Retro-peritoneal liposarcoma. About 5 cases and revue of literature].
AB  - Liposarcomas are malignant mesenchymatous tumors developed from elements
      constituting the greasy tissue in various stages of differentiation. It is one of
      the most frequent mesenchymatous sarcomas. Retro-peritoneum is a privileged site
      of development in 12 to 15% of cases. During 9 years, from 1994 till 2002, we
      have colligated and operated 5 cases of retro-peritoneal liposarcomas. Average
      age was 50 years (extremes 34 to 79 years) with a sex-ratio of 1.5. Diagnosis was
      late beyond 6 months. Abdominal pain and the appearance of an enormous mass (20
      cm) were the revealing signs. No imagery method allowed to evoke the diagnosis.
      The cyto-puncture realized once, was not able to determine with precision the
      histological type. Immunohistochimy occupies nowadays an important place to
      classify a sarcoma. Large surgical resection realized in 5 cases did not allowed
      the complete ablation of the tumour in 3 cases considering the advanced loco
      regional extension, which was at the origin of 3 recurrences. Well differentiated
      histological type was noted in 3 cases, myxoid type in a case and not
      differentiated type in a case.

PMID- 17042212
TI  - [Idiopathic renal vein thrombosis. About two cases].
AB  - Renal vein thrombosis is a rare pathology difficult to diagnose. It has quite
      various clinical expressions and biological consequences. The diagnosis is based
      upon radiologic explorations. This entity may have various causes. Detecting this
      condition may lead to restoration of renal function compromised by renal vein
      thrombosis. The treatment of renal vein thrombosis is mainly medical and based on
      anticoagulants. The role of fibrinolytic treatment is controversial. Surgery is
      exceptional. We report two cases of idiopathic thrombosis of the renal vein in
      adult patient. Also, we have done a review of the literature on this clinical
      syndrome and its diagnostic and therapeutic aspects.

PMID- 17042213
TI  - [Intra vesical explosion during an endoscopic resection of a vesical tumor].
AB  - The intra vesical combustion of hydrogen and oxygen, form one mixture of
      explosive gas. Intra vesicale explosion during trans urethral resection is one
      rare incident. Its most dangerous manifestation during is vesical rupture. We
      demonstrate one case of intra vesical explosion during one endoscopic resection
      of one in the anterior face tumor of bladder. Damages on bladder are small. By
      going back to literature, we try to discuss the origin of intra vesical hydrogen
      and oxygen as well as the different preventive measures.

PMID- 17042214
TI  - [Scleredema of Buschke. A case report].
AB  - Scleredema of Buschke is a rare disease whose aetiology remains unknown. It is
      characterised by symetric skin induration of the upper part of the body which
      usually resolve spontaneously. It can be associated with extra-cutaneous
      symptoms. We report a new case in a 55 year old women.

PMID- 17042216
TI  - [Common bile duct distomatosis managed by coelioscopic aproach. One case report].
AB  - Biliary distomatosis is caused by a parasitis of trematode family: the fascialo
      hepatica. It is a rare affection in Tunisia. The diagnostic is often done in the
      status phase. Adult parasite stay preferentially at biliary ducts, cause
      obstruction and cholangitis. The authors report a case of biliary treated
      successfully by laparoscopic procedure.

PMID- 17042215
TI  - [Thyrotoxicosis revelated by bilateral hip fracture].
AB  - Hyperthyroidism is an important cause of secondary osteoporosis and therefore of
      fractures. Nevertheless, facing an osteoporotic fracture, we do not
      systematically seek after such thyroid disorder in our daily practice. In this
      purpose, we report the case of 73 year old women, presented with a bilateral
      pathological femoral neck fracture. Investigations find a hyperthyroid related
      osteoporosis. Beyond orthopaedic treatment, radioiodine and bisphosphonate drugs
      were prescribed.

PMID- 17042217
TI  - [Tubo-ovarian actinomycosis. A report of two cases and literature review].
AB  - Actinomycosis is an infection due to an anaerobic Gram-positive bacilus bacteria:
      Actinomyces. Tubo-ovarian locallisation is rare. It more often appears clinically
      as a pseudo-tumoral and feverish syndrom, evoking wrongly a malignant tumoral
      pathology, and often leads to a mutilating surgical treatment. Intra-uterine
      device appears as the principal favorable factor of this pathology. Basing on two
      cases reported by the authors, and after literature review, physiopathology,
      clinical and paraclinical expression, and treatment of this affection are
      discussed. A set up is made.

PMID- 17042218
TI  - [Eccrine poroma of the scalp: A study of three cases].
AB  - The eccrine poroma is a rare benign sudoral tumour, which creates a fleshy
      formation. The diagnosis is made according to the anatomopathological study. The
      usual site is the sol, but in rare cases, other sites have also been reported.
      The authors report three cases of eccrine poroma localised in the scalp with
      literature review.

PMID- 17042219
TI  - The two faces of capital femoral epiphyseal injury--new treatment paradigms
      against the perceived myths.

PMID- 17042220
TI  - Functional outcome after major lower extremity amputation: a survey on lower
      extremity amputees.
AB  - The post-operatve course of amputees is poorly documented. This cross-sectional
      survey was unertaken to determine functional outcomes of 213 patients who had
      undergone either a below-knee or above-knee amputation from 2000 to 2002 in a
      state-hospital setting. The study comprises a self-constructed questionnaire and
      interview conducted by phone. Of the 213 amputees, 41 out of 61 documented
      telephone numbers of the patients were useful for contact. Only 30 amputees were
      available for the study as the remaining 11 had passed away. Included in the
      questionnaire was the modified Barthel Index, a measurement to assess the
      amputees' ability to carry out activities of daily living (ADL). It contains ten
      questions pertaining to ADL with a total score of 20 points. Two-thirds of the
      respondents (67%) use their prosthesis for less than six hours per day. The
      Barthel Index of 30 patients ranged from 9-20 (mean 17.7). However, the mean
      Barthel Index in those with and without prosthesis was 18.4 and 15.2
      respectively, but this difference was not significant. Half of the respondents
      were unable to maintain their pre-amputation jobs, while the remaining 50% were
      still able to work. Forty seven percent of amputees took less than a year to
      return to their activities, while 33% took between one to two years. Regarding
      the adequacy of preamputation information provided by the doctors, 73% amputees
      responded in the affirmative, while 27% felt otherwise. Amputees were still
      facing substantial disabilities following major amputation of the lower limb.
      Although 80% of respondents surveyed own prosthesis, the full use of prosthesis
      is suboptimal due to prosthetic-related problems. Most amputees had a good
      functional outcome based on the modified Barthel Index. Some amputees were
      unhappy as they felt that they were insufficiently informed regarding post
      amputation expectation prior to the amputation. Despite good support from family,
      the community support for amputees is still lacking.

PMID- 17042221
TI  - Alteration of foot temperature in diabetic neuropathy: is it another piece of
      puzzle?
AB  - Poor glycaemic control and the duration of diabetes mellitus are known to
      accelerate development and progression of neuropathy. Diabetic co-morbidities:
      hypertension and hyperlipidaemia, have been postulated to associate with
      development of neuropathy. A diabetic foot with low temperature and frequent
      exposure to low temperature environment has recently been hypothesized to be at
      higher risk to develop early neuropathy. This cross-sectional study is undertaken
      to identify risk factors for diabetic neuropathy and the association between foot
      temperature and development of diabetic neuropathy by using simple clinical
      examination in the outpatient setting. From April 18, to April 30, 2005,
      universal sampling method was used to select 134 diabetic patients (type 1 or
      type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic
      alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and
      family history of porphyria and hereditary sensorimotor neuropathy. The patient's
      duration of diabetes, glycaemic control status and the presence of co-morbids:
      hypertension and hyperlipidemia, were recorded. The temperature of the foot was
      measured by using thermo buddy. Of 134 patients representing Malaysian ethnic
      distribution with an equal number of males and females, 20.1% were in the age
      group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and
      educational groups respectively. Associations between diabetic neuropathy and
      glycaemic control (p = 0.018) and duration of diabetes (p < 0.05) were
      significant. However, hypertension, hyperlipidaemia and low foot temperature were
      not significantly associated with development of diabetic neuropathy. Poor
      glycaemic control is significantly associated with diabetic neuropathy. Foot
      temperature alteration is merely an effect of autonomic neuropathy with a cold
      foot is attributed to co-existing peripheral arterial disease.

PMID- 17042222
TI  - Bacteriology of diabetic foot lesions.
AB  - Infection plays a pivotal role in enhancing a diabetic foot at risk toward
      amputation. Effective antibiotic therapy against the offending pathogens is an
      important component of treatment of diabetic foot infections. Recognition of the
      pathogen is always difficult as the representative deep tissue sample for culture
      is surrounded by ulcer surface harbouring colonies of organisms frequently
      labelled as skin commensals. The emergent of resistant strains represents a
      compounding problem standing against efforts to prevent amputation. This study
      was undertaken to identify the pathogens associated with diabetic foot infection
      in terms of their frequency and sensitivity against certain commonly used
      antibiotics. Forty-four consecutive patients with open diabetic foot infections
      had wound swab taken for culture and sensitivity testing. Cultures positive were
      observed in 89% of the cases with Staphylococcus aureus, Klebsiella pneumoniae,
      Pseudomonas aeroginosa encountered in 20%, 14% and 14% of cases respectively.
      Mixed growths were isolated in 6% of cultures. All Staphylcoccus aureus isolates
      were resistant to Penicillin but 80% were sensitive to Erythromycin and Co
      trimoxazole. Klebsiella pneumoniae isolates were sensitive to Methicillin and
      Gentamycin in 80% and 60% of cases respectively, and resistant to Ampicillin and
      Ceftazidime in 83% and 50% respectively. All Pseudomonas aeroginosa isolates were
      sensitive to Amikacin and Ciprofloxacin but 50% were resistant to Gentamycin.
      There was no single antibiotic possessing good coverage for all common organisms
      isolated from diabetic foot lesions. Staphylococcus aureus remains the
      predominant cause of diabetic foot infections followed by Klebsiela pneumonia and
      Pseudomonas aeroginosa. Most infections are monomicrobial. The emergence of
      multiresistant organisms is a worrying feature in diabetic foot infections.

PMID- 17042223
TI  - Necrotizing fasciitis of the lower limb: an outcome study of surgical treatment.
AB  - Necrotizing fasciitis is a limb- and life-threatening rapidly spreading infection
      affecting the deep fascia with secondary necrosis of the subcutaneous tissue. It
      requires immediate medical attention and emergency surgery to prevent morbidity
      and death. This study was undertaken to determine its co-morbidity and risk
      factors affecting the outcome of its surgical treatment. This is a retrospective
      review of 36 cases of necrotizing fasciitis of the lower limb treated in our
      center between 1998 and 2002. Only 19% of the cases were correctly diagnosed upon
      admission and 48.6% were initially diagnosed as 'cellulitis'. Diabetes mellitus
      was the most common co-morbid. Pseudomonas, Staphylococcus, Streptococcus and
      Enterobactericae were the common pathogens isolated. Ten patients (27.8%) had
      major amputation as part of radical debridement. The overall mortality rate was
      36% with laboratory parameters: high serum urea and creatinine, and low
      haemoglobin levels were predictors for higher mortality. Poor white cell response
      which is common in diabetic patients and a delay in surgical debridement were.
      notable attributes to a higher mortality. Necrotizing fasciitis is a serious
      infection associated with significant morbidity and mortality. A poor white blood
      cell response, high serum urea and creatinine, and low haemoglobin level were the
      predictors for mortality. Early diagnosis and prompt treatment are of paramount
      importance in the treatment of this infection.

PMID- 17042224
TI  - Antimicrobial properties of erythromycin and colistin impregnated bone cement. An
      in vitro analysis.
AB  - Deep surgical site infection is a devastating consequence of total joint
      arthroplasty. The use of antibiotic impregnated bone cement is a well-accepted
      adjunct for treatment of established infection and prevention of deep orthopaedic
      infection. It allows local delivery of the antibiotic at the cement-bone
      interface and sustained release of antibiotic provides adequate antibiotic
      coverage after the wound closure. Preclinical testing, randomised and clinical
      trials indicate that the use of antibiotic-impregnated bone cement is a
      potentially effective strategy in reducing the risk of deep surgical site
      infection following total joint arthroplasty. The purpose of this study was to
      assess antibacterial activity of erythromycin and colistin impregnated bone
      cement against strains of organisms' representative of orthopaedic infections
      including Gram-positive and Gram-negative aerobic organisms: Staphylococcus
      aureus, coagulase-negative Staphylococci, Enterococcus sp., Proteus sp.,
      Klebsiella sp., Pseudomonas sp., and Escherichia coli. Pre-blended Simplex P bone
      cement with the addition of erythromycin and colistin (Howemedica Inc) was mixed
      thoroughly with 20ml liquid under sterile conditions to produce uniform
      cylindrical discs with a diameter of 14mm and thickness of 2mm. 24-48 hour agar
      cultures of Staphylococcus aureus, coagulase-negative Staphylococci, Enterococcus
      sp.,Proteus sp., Klebsiella sp.,Pseudomonas sp., and Escherichia coli were used
      for the agar diffusion tests. The agar plates were streaked for confluent growth
      followed by application of erythromycin and colistin impregnated bone cement disc
      to each agar plate. The plates were incubated at 30 degrees C and examined at 24,
      48, 72 hours, and four and five days after the preparation of the impregnated
      cement. The susceptibility of Staphylococcus aureus to the control discs was most
      clearly demonstrated showing a distinct zone of inhibition. The zone observed
      around coagulase-negative Staphylococci, Klebsiella sp., Pseudomonas sp., and
      Escherichia coli were also significant. However, there was no zone of inhibition
      or signs of antibacterial activity at the cemented surface were detected around
      discs with Enterococcus sp. and Proteus sp. The results showed that Simplex P
      bone cement with the addition of erythromycin and colistin was effective against
      most of the broad spectrum organisms encountered during total joint arthroplasty.
      The activity of Simplex P bone cement impregnated with erythromycin and colistin
      is mainly during the first 72 hours.

PMID- 17042225
TI  - Biomechanical properties of bone cement with addition of cefuroxime antibiotic.
AB  - Antibiotic-loaded bone cement has been used as prophylaxis against infection in
      total joint replacement surgery. Its effect on the mechanical strength of cement
      is a major concern as high dose of antibiotic was associated with a significant
      reduction in mechanical strength of bone cement. However, the cut-off antibiotic
      that weakens the mechanical strength of cement remains to be determined. This
      study was undertaken to observe the changes in the mechanical properties of bone
      cement with gradual increments of Cefuroxime antibiotic. Cefuroxime at different
      doses: 0, 1.5, 3.0 and 4.5gm were added to a packet of 40gm bone cement (Simplex
      P) and study samples were prepared by using third generation cementing technique.
      Mechanical impact, flexural and tensile strength were tested on each sample.
      Significant impact and tensile strength reduction were observed after addition of
      4.5 gm of Cefuroxime. However, flexural strength was significantly reduced at a
      lower dose of 3.0 gm. The maximum dose of Cefuroxime to be safely added to 40mg
      Surgical Simplex P is 1.5gm when third generation cementing technique is used.
      Further study is needed to determine whether it is an effective dose as regards
      to microbiological parameters.

PMID- 17042226
TI  - Spinal injuries in a level-one trauma centre: a demographic study.
AB  - The incidence of spinal injuries in Malaysia is on the rise following similar
      trend of rapid development and increasing number of building constructions sites,
      and motor vehicles. This epidemiological study was aimed at compiling local data
      with a view to identifying target areas for preventive measures as well as
      improvement strategies in the management of these potentially devastating
      injuries. Seventy eight patients admitted with spine trauma in 1998 in a level
      one trauma centre were retrospectively reviewed. All records were traced from the
      admission and discharge books of the orthopaedic wards, accident and emergency
      wards, operative registration book, spinal rehabilitation ward and orthopaedic
      registration data of the Department of Orthopaedics, Hospital Kuala Lumpur.
      Details on pre-treatment neurological and radiological level of injury and post
      treatment outcomes were recorded according to the American Spinal Injury
      Association (ASIA) impairment scale. Most patients (61.5%) were in the productive
      ages of less than 34 years with a 4:1 male to female ratio. Majority were due to
      motor vehicle accidents (57.7%) and fall from a height (28.3%). The thoraco
      lumbar junction was the most common site of injury followed by the lower cervical
      region with 62.5% of which associated with neurological deficit. Neurological
      deficits: 11 ASIA-A, 1 ASIA-B, 6 ASIA-C, and 3 ASIA-D were detected in 21 (27%)
      patients with fall from height (50%) particularly landing on the feet (50%) and
      recreational sports (100%) were the risk factors. Less than 10% of patients were
      treated surgically and this explains an average 39.4 days of hospitalization (5
      times longer in patients treated non-operatively). On discharge, four patients
      with incomplete neurology recovered to ASIA-E status and the remaining improved
      to ASIA-C and -D in one and five patients respectively. Only one patient with
      complete neurology improved to ASIA-B status following surgical treatment. The
      demographic profiles of our patients were comparable to other series in the
      literature but still inadequate to provide enough epidemiological data. A
      multicenter study to provide a larger pool of patients is needed.

PMID- 17042227
TI  - Sliding compression screw fixation for delayed union/non-union of femoral neck
      fracture: is it a viable option.
AB  - Femoral neck fracture non-unions often present with significant difficult
      treatment decision as regards to surgical options and the risk of complication.
      We present three cases of femoral neck non-union treated with double screw
      stabilization technique using sliding compression hip screw and anti-rotational
      screw. The rationale for opting to these simple implants in our setting is
      discussed.

PMID- 17042228
TI  - Screw osteosynthesis of displaced lateral humeral condyle fractures in children:
      a mid-term review.
AB  - Displaced humeral condyle fractures in children are traditionally fixed with
      smooth Kirschner wire at the expense of a risk of secondary displacement
      following removal of wire. Screw fixation of such fractures has recently been
      advocated as it provides stable fixation. We have been using screw osteosynthesis
      for treatment of displaced lateral humeral condyle fractures in children in our
      institution since the turn of this century. This study provides a midterm review
      of treatment of such injuries with special regards to growth disturbances after
      screw osteosynthesis and to assess rate of union with a view to formulate
      guidelines for screw removal. We review the outcomes of screw osteosynthesis for
      displaced lateral condyle fracture of the humerus (19 Milch type-1 and 15 Milch
      type-II) in 34 children treated in our institution from January 2000 to March
      2004. The average age of the patients was 6.1 years. The average follow up was
      24.5 months. Screw osteosynthesis led to union (average 6.9 weeks) in all
      patients with excellent results in 28 patients. Growth disturbances in the form
      of lateral condyle overgrowth (2 patients), valgus deformity secondary to lateral
      condyle avascular necrosis (2 patients) and fishtail deformity ((3 patients) were
      recognized. The implants should not be removed until fracture union is
      established. Screw osteosynthesis of the lateral humeral condyle fracture
      prevents secondary fracture redisplacement and lateral condyle overgrowth is
      probably related to hyperemic response to metaphyseal fixation and early removal
      of implant before radiological union.

PMID- 17042229
TI  - Adequacy of pain relief in closed manipulative reduction of fracture and
      dislocation.
AB  - Adequate pain relief is a requisite for a successful closed manipulative
      reduction (CMR) of fractures and dislocations. This prospective study was
      undertaken to assess the mode and adequacy of pain relief given to patients
      undergoing such procedures at Seremban Hospital from the 1st April to the 31st
      May 2001. All patients with fractures and dislocations scheduled to undergo CMR
      were included in this study. The type of sedative agents and analgesia
      administered were recorded. Demographic data and the type of fracture or
      dislocation of the selected patients were documented. A visual analogue scale
      (VAS) for pain perception was given to both to the patients and the medical
      personnel who performed the procedure. All data were collected manually before
      entered into computerized database for analysis. Of 72 patients included in this
      study, 47% were Malay, 26% Indian, 21% Chinese and 6% others. There was male
      predominance and the patients' age ranged between 9 to 79 years (average 27.4
      years). Upper limb injuries (79%) were mainly fractures of the radius and ulna
      (29%) and isolated fracture radius (21%). For the lower limb injuries (21%),
      combined tibia and fibula fractures constituted 10% of the total cases followed
      by isolated tibia fractures (10%) and hip dislocation (1%). The most common pain
      relieving agents given during the CMR were intravenous pethidine alone (43%)
      followed by combination of intravenous pethidine and valium (36%), intramuscular
      pethidine (17%) and intramuscular tramal (4%). The Visual Analogue Score (VAS)
      for pain perception revealed that 61% of the patients had moderate pain while 21%
      had severe pain during the course of the procedures. Suboptimal pain relief
      administered during CMR should prompt positive actions to ensure that the patient
      is not subjected to undue pain just for the sake of an acceptable fracture
      reduction.

PMID- 17042230
TI  - Radiation exposure to operating theatre personnel during fluoroscopic-assisted
      orthopaedic surgery.
AB  - Orthopaedic procedures especially dynamic hip screw (DHS) fixation, interlocking
      nailing (ILN) of the tibia and femur require fluoroscopic assistance. Frequent
      exposure to radiation is a major concern to members of the orthopaedic surgical
      team. This study was undertaken to measure shallow (skin) dose to the operating
      team personnel and deep (whole body) dose to the surgeon during such procedures
      in view to provide guidelines to the operating team members regarding the number
      of procedures allowable for them to perform or assist annually. Skin dose for the
      operating personnel and whole body dose for the operating surgeon during 25
      procedures; ten cases of DHS, seven and six cases of ILN of the tibia and femur
      respectively, was measured using Thermoluminescent Dosimeter (TLD) chips. The
      shallow radiation dose for theatre personnel ranged from 0.19 mSy to 0.61 per
      case while the deep dose for the surgeon was 0.28, 0.55 and 0.81 mSy for seven
      cases of tibial ILN, ten cases of DHS and six cases of femur ILN respectively.
      The surgeon has the highest radiation exposure than other theatre personnel and
      the whole body exposure for DHS was higher than that of for ILN. However, the
      estimated cumulative dose was still far below the permissible annual dose limit.

PMID- 17042231
TI  - Delay in treatment of primary malignant and aggressive musculoskeletal tumours.
AB  - Patients with aggressive musculoskeletal tumours often arrive at specialised
      treatment centres late. Such a delay could mean disfavour for potentially curable
      or long-term disease-free outcome of limb preserving surgery. This study was
      undertaken to identify the underlying problem-related delay with a view to
      propose solution for solving it. We reviewed 30 patients to determine the periods
      of delay between onset of the first symptom and the definitive treatment. The
      delays were categorized as 'patient' delay, 'referral' delay and 'treatment'
      delay. There was 'patient' delay in 57% of patients (n=17), ranging from 1 to 18
      months; 'referral' delay in 67% of patients (n=20) ranging from 1 to 19 months
      and 23% of patients (n=7) had treatment delay (average 23 days) at the treatment
      centre. The causes of late arrival are not solely patient-related but are
      multifactorial. Measures to minimize such delays include enhancing awareness only
      with high index of suspicion among primary care practitioners, creating a special
      lane specialized imaging studies and establishing a dedicated musculoskeletal
      tumour unit.

PMID- 17042232
TI  - Forequarter amputation of the upper extremity for musculoskeletal tumors:
      posterior approach revisited.
AB  - Forequarter amputation entails surgical removal of entire upper extremity,
      scapula and clavicle. Several techniques of forequarter amputation have been
      described. The anterior approach has been the preferred technique of exploration
      of axillary vessels and brachial plexus. The posterior approach has been
      condemned to be unreliable and dangerous for most large tumor of the scapula and
      suprascapular area. We describe a surgical technique using posterior approach of
      exploration of major vessels for forequarter amputation of upper extremity in
      eight patients who presented with humeral-scapular tumor. There were six patients
      with osteosarcoma: three with tumor recurrent and three chemotherapy recalcitrant
      tumors with vessels involvement. One patient had massive fungating squamous cell
      carcinoma and another had recurrent rhabdomyosarcoma. Four patients had fungating
      ulcer and six patients had multiple pulmonary metastases at the time of surgery.
      The mean estimated blood transfusion was 900 ml (range 0-1600 ml) and two
      patients did not require transfusion. The duration of surgery ranged 2.5-6.0
      hours (mean 3.8 hours). Two patients with known pulmonary metastases required
      post-operative intensive care monitoring. The mean duration of survival was 5.8
      months. The posterior approach of exploring major vessels for forequarter
      amputation of upper extremity with musculoskeletal tumor is safe and reliable.

PMID- 17042233
TI  - A simple practical protocol for care of metal-skin interface of external
      fixation.
AB  - Patients treated with external fixation for limb reconsturciton or fracture
      stabilization equire regular and prolongedperiod of pin-tract care involving
      frequent visits to clinic and dressing traditionally carried out by trained
      nurses or medical assistants. A simple method of do-it-yourself dressing was
      introduced in our institution and this study was undertaken to evaluate the
      effectiveness of the protocol. Sixty patients (40 trauma-related problems and 20
      congenital or developmental disorders) were enrolled into the study. Following
      application of external fixation, the patients and/or their caretakers were
      taught on how to do pin-site dressing using normal saline or drinking water as
      cleansing solution on daily basis. Patients were discharged on the second or
      third post-operative day and were followed-up every two weeks for an average 182
      days (range 66 to 379 days) with special attention on identifying pin-tract
      infection. A simple grading system for pin-tract infections was proposed. Of 40
      patients with trauma-related problems. 65% were post-traumatic infections. There
      were 788 metal-skin interfaces (239 half-pin fixations and 549 tensioned wire
      fixations. A total 143 metal-skin interface infections (18.1%) involving half-pin
      sites (41.3%) and tensioned wire sites (58.7%) was noted. Majority were grade I
      infections (79.7%), 18.8% grade II and only 1.4% grade III. Most infections
      (81%)were caused by Staphylococcus aureus. Grade I infections were successfully
      treated with frequent dressing, grade II by adjunctive oral antibiotic but grade
      III infections required removal of fixator. All eventually healed. Do yourself
      non-sterile dressing of metal-skin interfaces is a cost-effective method of pin
      site care with a low infection rate. The infections were sucessfully treated
      using guidelines according to the proposed classification of pin-tract
      infections.

PMID- 17042234
TI  - Recalcitrant post-traumatic chronic osteomyelitis/infected non-union of the tibia
      following open grade-ill fractures: treatment with vascularized osteocutaneous
      fibular graft.
AB  - Post-traumatic chronic osteomyelitis and infected non-unions of the tibia
      following severe type-III open fracture are difficult to treat Refractoy cases
      often necessitate amputation despite attempts to salvage the limb. We report our
      experience in treating such difficult cases with an alternative surgical option
      using free osteocutaneous fibular graft. Eight consecutive patients with post
      traumatic chronic osteomyelitis/infected non-union were treated surgically with
      free vascularized osteocutaneous fibular graft. Outcomes in term of graft-host
      union and complication were evaluated. Four patients had anastomotic venous
      thrombosis requiring anastomotic revision. Five patients developed surgical site
      infections needing extended antibiotic therapy to achieve resolution at an
      average of 15.2 weeks. Fibular graft fracture occurred in three patients but all
      grafts survived and united after a mean time to union of 42.3 weeks (range 31 to
      82 weeks). At the final follow-up, union of host-graft junction and control of
      infection were achieved in all patients except one who required a secondary
      amputation. Free vascularized osteo-cutaneous fibular graft is a viable limb
      salvage option for refractory chronic osteomyelitis or infected non-union
      following treatment of grade-III open tibial fractures.

PMID- 17042235
TI  - Slipped capital femoral epiphysis (SCFE): a 12-year review.
AB  - Slipped capital femoral epiphysis (SCFE) is a relatively uncommon hip disorder in
      adolescents and its prevalence in Malaysia has not been studied. This
      retrospective study is undertaken to provide an overview of a 12-year review of
      SCFE treated in our institution. Fourteen patients (19 hips) with slipped capital
      femoral epiphysis (SCFE) admitted to Hospital UKM from 1990 to 2002 were reviewed
      with respect to demographic profile, functional outcome according to the Iowa Hip
      Score, and complications. There were ten boys (average age, 12.5 years) and four
      girls (average age, 12 years). Eight were Malays and six were Indians. The
      average body mass index was 26.1 verweight). The left hips (11 hips) were
      affected more than the right hips (eight hips). Five patients had bilateral
      slips. Thirteen hips were considered stable while the other six hips were
      unstable. The majority of cases were moderate slips (12 hips), four hips had
      severe slips while three hips had mild slips. Several methods of treatment were
      instituted. These include in situ cannulated screw fixation (11 hips), Knowles
      pin fixation (three hips) and gentle closed manipulative reduction with
      cannulated screw fixation (three hips). One patient with bilateral slips refused
      surgical treatment. Based on the Iowa Hip Score, most patients (nine) had
      satisfactory results (excellent or good), three had fair results while one
      patient had a poor result. Avascular necrosis developed in five hips while
      chondrolysis occurred in one hip. In situ cannulated screw fixation is the
      treatment of choice. SCFE is an uncommon condition in Malaysia.

PMID- 17042236
TI  - The pattern of femoral diaphyseal fractures in children admitted in Sarawak
      General Hospital.
AB  - Trend towards changing the face of management for pediatric femoral fractures
      tends to advocate operative treatment. This study was undertaken to review our
      current practice in the wake of recent progress in the management of pediatric
      femoral fractures. Fifty patients with femoral diaphyseal fracture treated in
      Sarawak General Hospital were reviewed retrospectively after an average follow-up
      of 2.6 years. There were 36 boys and 14 girls, with a mean age of 6.2 years
      (range five months to 14 years). Children under six years of age constituted the
      majority of the patients. Half of the fractures were caused by road traffic
      accident. Nine patients had associated injuries. The most common site of fracture
      was at the middle third (N=31). The treatment regimens were delayed hip spica
      (DHS) in 16, immediate hip spica (IHS) in 24, plate osteosynthesis (PO) in five,
      titanium elastic nailing (TEN) in five, and external fixation (EF) in one. The
      minimum hospital stay was two days, and the maximum 33 days (mean, 9.7 days).
      Malunion was the commonest complication. Conservative treatment is the preferred
      option for children under six years of age. It is cost-effective with minimal
      complication. The other treatment options are reserved for specific indication in
      older children. Diaphyseal fractures of the femur in children can be adequately
      managed non-operatively.

PMID- 17042237
TI  - Apollo total knee replacements in University Malaya Medical Centre: a short-term
      outcome.
AB  - Total knee arthroplasty is the most preferred option for treatment of severe
      osteoarthritis of the knee. We report the short-term outcome of 48 total knee
      replacements in 31 patients utilizing the Apollo Total Knee System after an
      average follow-up of 48 months (range 15 to 70 months). Records of all patients
      who underwent TKA using Apollo Total Knee System were retrospectively reviewed.
      Functional outcome was evaluated using visual analogue scale for pain rating and
      the Oxford 12-item questionnaire. Postoperative radiographs of the replaced knees
      were assessed by using the Knee Society Total Knee Arthroplasty Roentgenographic
      Evaluation and Scoring System. Degenerative osteoarthritis was the commonest
      indication for TKA. The average patient's age was 63.7 years (range, 30-77
      years). The mean visual analogue scale for pre- and post-operative pain was eight
      and zero respectively. The mean Oxford 12-item questionnaire score pre- and post
      operatively was 44.8 and 16.5 respectively. Patient satisfaction was notable in
      98% of the cases with an average improvement in arc of flexion of 111 degrees.
      There were four failures; deep infection (one) and aseptic loosening (three)
      giving rise to a 94% implant survivor. The short-term results of this series is
      comparable with or better than a number of outcome studies of the Apollo Knee
      System or other implants of similar design.

PMID- 17042238
TI  - Venous gas embolism following hydrogen peroxide irrigation during debridement of
      chronic osteomyelitis lesion.
AB  - We report a case of a previously healthy 53-year-old man who developed an intra
      operative catastrophic event occurring in association with the use of hydrogen
      peroxide for wound irrigation following surgical debridement of a chronic
      osteomyelitis lesion of the humerus. It is our intention to highlight this
      potentially fatal consequence of hydrogen peroxide irrigation as part of bone
      debridement procedure. This case will serve as a reminder to orthopaedic surgeons
      who frequently use hydrogen peroxide in their surgical practice.

PMID- 17042239
TI  - Marjolin's ulcer--a near forgotten entity.
AB  - We report a case of a 55-year-old man who presented with a 6-month history of a
      fungating ulcer on the right hand at the site of a previously healed ulcer that
      had been present for 40 years. Histopathological examination of four-quadrant
      biopsy specimens showed a moderately differentiated squamous cell carcinoma
      (SCC). A transradiocarpal amputation with stump closure using radial flap was
      performed as it was not possible to achieve a functionally and cosmetically
      acceptable hand after a wide excision with 2 cm tumour-free margin. It is our
      intention to highlight this rare condition as reminder to consider this entity as
      a differential diagnosis of chronic non-healing skin ulcer.

PMID- 17042241
TI  - Bilateral femoral neuropathy associated with disseminated intravascular
      coagulopathy: a case report.
AB  - We report a case of 20-year-old man who presented with bilateral femoral nerve
      palsy following resuscitation for traumatic massive blood loss and its
      consequence. A high suspicious index for this complication may lead to its early
      recognition. Its related pathoanatomy is discussed based on the described
      evidences in the literature. Nonoperative treatment remains as a recommended
      option for coagulopathy-related neuropathy.

PMID- 17042240
TI  - Transphyseal fracture-separation of the femoral capital epiphysis: a true SCFE of
      traumatic origin.
AB  - Acute traumatic transphyseal fracture of the capital femoral epiphysis is a rare
      but serious injury. The injury is typically inflicted by a severe trauma. Because
      of the vulnerability and predisposed anatomy of the femoral epiphysis in relation
      to its blood supply, the fracture has been designated to have poor prognosis with
      inevitable osteonecrosis and eventual deformity of the hip. We report a case of
      such fracture in a 13-year-old child in view to highlight some of the anticipated
      problems in the management of such injury.

PMID- 17042242
TI  - Revision total hip arthroplasty using impaction bone grafting technique.
AB  - A variety of reconstructive options exist for revision of both femoral and
      acetabular components in total hip replacement surgery. The use of impaction bone
      grafting with morsellised allograft has shown promising results in revision total
      hip arthroplasty. It works as a biologic reconstitution of bone stock defects and
      provides a solid construct with stable fixation. We present a case of bilateral
      revision total hip arthroplasty with poor bone stock where reconstructive surgery
      was done by using impaction bone grafting, mesh and C-stem implants.

PMID- 17042243
TI  - Delayed treatment of decompression sickness with short, no-air-break tables:
      review of 140 cases.
AB  - INTRODUCTION: Most cases of decompression sickness (DCS) in the U.S. are treated
      with hyperbaric oxygen using U.S. Navy Treatment Tables 5 and 6, although
      detailed analysis shows that those tables were based on limited data. We reviewed
      the development of these protocols and offer an alternative treatment table more
      suitable for monoplace chambers that has proven effective in the treatment of DCS
      in patients presenting to our facility. METHODS: We reviewed the outcomes for 140
      cases of DCS in civilian divers treated with the shorter tables at our facility
      from January 1983 through December 2002. RESULTS: Onset of symptoms averaged 9.3
      h after surfacing. At presentation, 44% of the patients demonstrated mental
      aberration. The average delay from onset of symptoms to treatment was 93.5 h;
      median delay was 48 h. Complete recovery in the total group of 140 patients was
      87%. When 30 patients with low probability of DCS were excluded, the recovery
      rate was 98%. All patients with cerebral symptoms recovered. Patients with the
      highest severity scores showed a high rate of complete recovery (97.5%).
      DISCUSSION: Short oxygen treatment tables as originally described by Hart are
      effective in the treatment of DCS, even with long delays to definitive
      recompression that often occur among civilian divers presenting to a major Divers
      Alert Network referral center.

PMID- 17042244
TI  - Venous filling and elastance in the calf positioned above and below heart level.
AB  - INTRODUCTION: Limb venous compliance is a major factor in determining the extent
      of blood pooling during orthostatic stress. We measured the filling of the calf
      and of its major veins at different postures and quantified the venous
      contribution to the total volume shift of the calf. The results were also used to
      determine the venous elastance and to gain some information on the filling of the
      small veins. METHODS: Twelve healthy volunteers participated in the study. The
      calf volume was measured with strain gauge plethysmography and the veins were
      imaged with ultrasound in the following positions: supine, sitting with both legs
      horizontal, sitting with one leg suspended, and supine with one leg raised. Cross
      sectional areas of the imaged veins were calculated from the measured diameters.
      Hydrostatic change in the venous pressure was assumed when calculating the venous
      elastance. RESULTS: The maximal increase in the calf area was up to 1 cm2. The
      large veins accounted for approximately 30% of the total volume shift of the calf
      except in cases where the subjects had one leg suspended. Then, the contribution
      of the large veins was less than 20%. The estimated elastance of the large veins
      was 80 +/- 14 mmHg, which may be regarded as substantial. CONCLUSIONS: The study
      suggests that there is a distinct difference in the filling of the small and the
      large leg veins. The small veins may be the principal contributors to the total
      compliance of the calf when the venous pressure is above 30 mmHg.

PMID- 17042245
TI  - Cardiovascular regulation response to hypoxia during stepwise decreases from 21%
      to 15% inhaled oxygen.
AB  - INTRODUCTION: The classical view states that hypoxia beyond an oxygen
      concentration of about 17% induces tachycardia. However, few studies have
      investigated the dose-dependent effects of acute normobaric hypoxia on autonomic
      nervous regulation of the cardiovascular system. Therefore, we evaluated the
      effects of stepwise hypoxia on cardiovascular neural regulation and postulated
      that acute normobaric hypoxia causes vagal withdrawal and sympathetic activation
      from 17% 02. METHODS: There were 18 healthy men who were exposed to acute
      stepwise normobaric hypoxia (21%, 19%, 17%, 15% 02). Spectral analysis of the RR
      interval and BP variability were used. RESULTS: BP was not altered. Heart rate
      significantly increased at 15% (21%, 59 +/- 2; 15%, 62 +/- 2 bpm). The low
      frequency power of systolic BP variability (an index of vasomotor sympathetic
      nerve activity) significantly increased at 15% (21%, 6.1 +/- 1.3; 15%, 9.9 +/-
      1.3 mmHg2). The low-frequency power of the RR interval variability significantly
      increased from 17% (21%, 1036 +/- 233; 17%, 1892 +/- 409; 15%, 1966 +/- 362 ms2),
      However, the high-frequency power of RR interval variability (an index of cardiac
      parasympathetic nerve activity) did not change. Associated with these changes,
      the ratio of low- to high-frequency power of RR interval variability as an index
      of relative cardiac autonomic balance significantly shifted toward sympathetic
      dominance (21%, 1.5 +/- 0.3; 15%, 2.2 +/- 0.3). All indices of cardiac baroreflex
      function (transfer function and sequence gains) were unchanged. DISCUSSION: These
      results suggest that acute exposure to normobaric mild hypoxia (O2 > or = 15%)
      induces increases in sympathetic vasomotor activity and cardiac sympathetic
      dominance resulting in an increased heart rate. However, 15% O2 hypoxia might not
      induce changes in static BP, vagal activity, or spontaneous arterial-cardiac
      baroreflex function.

PMID- 17042246
TI  - The sweating foot: local differences in sweat secretion during exercise-induced
      hyperthermia.
AB  - INTRODUCTION: Little is known regarding local differences in foot sweat
      secretion. Since such information is important to our understanding of sweat
      gland control for thermoregulatory modeling and for the design of footwear we
      explored this topic. METHODS: Local sweat rates were investigated across core
      temperatures from 37-39 degrees C, achieved using endogenous (cycling) and
      exogenous heat (water-perfusion garment: 46 degrees C). Six healthy adults (three
      men, three women) performed one-legged, incremental cycling in a heated, climate
      controlled chamber (36 degrees C, 60% relative humidity). Sweat rates were
      measured at the forehead and stationary (left) foot (capsules 3.16 cm2): three
      dorsal sites (base of toes, second metatarsal, and mid point), the lateral, and
      the central plantar surfaces. RESULTS: Terminal core temperatures ranged between
      38.3-39.1 oC, with peak heart rates of 155-187 bpm. Most foot sweat rates were <
      50% of that observed at the forehead: dorsal 1 (38%); dorsal 2 (54%); dorsal 3
      (37%); lateral (24%); and plantar surfaces (18%). When averaged across the trial,
      local sweat rates were: 2.61 (forehead); 0.98 (dorsal 1); 1.39 (dorsal 2); 0.95
      (dorsal 3); 0.62 (lateral); and 0.47 mg cm2 2 min-1 (plantar). CONCLUSION: Two
      key observations emerged. First, sweat secretion from the experimental foot
      averaged 30 ml x h(-1), peaking in the last 5 min at 50 ml x h(-1). Second,
      approximately 70% of the measured sweat flow emanated from the upper skin
      surfaces, with only 30% coming from the plantar surface.

PMID- 17042247
TI  - CO2 detection in closed-circuit oxygen divers with and without a distracting
      task.
AB  - INTRODUCTION: Elevated arterial PCO2 (hypercapnia) increases the risk of CNS
      oxygen toxicity when diving with enriched oxygen gas mixtures. A CO2 detection
      and retention test is conducted as a matter of routine at the Israel Naval
      Medical Institute for physiological training, and as a screening tool for divers
      who may be prone to suffer from CNS oxygen toxicity. This test does not include
      an "attention distracter", which would provide a better simulation of the true
      situation during actual diving. The purpose of the present study was to examine
      the hypothesis that the addition of cognitive tasks to the CO2 detection and
      retention test might alter divers' detection ability. METHODS: We assessed
      ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6
      kPa, 0-42 mmHg) during moderate exercise, with and without the addition of
      cognitive tasks, in 15 Israel Navy combat divers on active duty. The first stage
      was the CO2 detection training session, followed by the CO2 detection test
      session (TEST) and the CO2 detection test session while doing cognitive tasks
      (COGN). The latter two sessions were performed by some of the subjects in reverse
      order. RESULTS: We found that the mean (+/- SD) PICO2 at the detection threshold
      was significantly lower in the COGN (1.7 +/- 0.8 kPa, 12.7 +/- 6.0 mmHg) than in
      the TEST (2.4 +/- 0.6 kPa, 18.1 +/- 4.5 mmHg). The mean PETCO2 while inspiring
      5.6 kPa (42 mmHg) CO2 was not significantly different in the two tests.
      CONCLUSION: We suggest that the ability to detect CO2 during a dive is not
      impaired, but rather improves when the diver's attention is focused on other
      tasks.

PMID- 17042248
TI  - Caffeinated tube food effect on pilot performance during a 9-hour, simulated
      nighttime U-2 mission.
AB  - INTRODUCTION: Interventions to maintain performance are necessary to meet
      demanding mission requirements during sustained and surge aviation operations.
      Tube foods are the only foods that can be consumed during a U-2 mission due to
      the confining and encapsulating nature of required support equipment. Caffeine is
      a safe and effective strategy to enhance cognitive performance and is an
      ingredient in some tube foods. The objective of this study was to determine
      whether moderate doses of caffeinated tube foods would enhance performance in a
      simulated U-2 mission. METHODS: Volunteers were 12 healthy USAF male pilots. The
      study used a double blind, placebo-controlled, two-factor, repeated-measures
      (five iterations per night) design. Caffeinated (200 mg each) or placebo tube
      food was consumed at 00:00 and 04:00. Dependent measures assessed included
      standardized tests of cognitive performance, vigilance, and mood designed to
      simulate the demands of a nighttime U-2 mission. RESULTS: Statistically
      significant (p < 0.05) improvements in performance due to caffeine administration
      compared with placebo were present in all five cognitive tasks either as main
      effects, interactions, or absence of significant degradation in the caffeine
      treatment condition compared with the placebo condition. A majority of sleep
      deprivation-induced performance decrements were attenuated by 200 mg of caffeine
      in tube food consumed every 4 h, and in some cases, performance was improved
      beyond baseline levels. CONCLUSIONS: Caffeinated tube food maintained cognitive
      performance representative of U-2 long-duration mission tasks at or near baseline
      levels for a 9-h overnight period in qualified USAF pilots. Side effects were
      minor and did not differ between placebo and caffeine conditions.

PMID- 17042249
TI  - Head rotation during vertical impact predicted using initial head angle and
      anthropometry.
AB  - INTRODUCTION: Dynamic inertial loading to the head and neck complex, similar to
      what is experienced during the rocket boost phase of pilot ejection, results in
      diverse kinematic responses when observed in live human volunteers. The purpose
      of this study was to develop a predictive model of head rotation during the
      compressive phase of pilot ejection. METHODS: Post hoc analyses were conducted on
      data from two previous experimental studies. This analysis included observing 138
      tests involving 27 human volunteers (both men and women) where the various
      kinematic responses were categorized into five modes based on the location of
      primary rotation and the direction of head rotation. Several statistical methods
      (logistic regression, linear regression, and Fisher's Exact test) were employed
      to evaluate the influence of independent variables, body anthropometry, and
      initial head angle on dependent variables head acceleration and direction of head
      rotation. RESULTS: Statistical results of this data indicated that initial head
      position and body anthropometry are significant factors with respect to head
      response during the compressive phase of an ejection. Two statistical tools were
      developed; one to assist in predicting the location of primary head rotation, and
      the other to predict the direction of head rotation. DISCUSSION: By using the two
      statistical tools together, a simplified method was developed for predicting the
      modes of head response to vertical impact based on initial position and
      anthropometry. The results of this study show the importance of initial position
      prior to an ejection and may assist in identifying individuals at greater risk of
      injury during an ejection.

PMID- 17042250
TI  - Neck muscle activation and head postures in common high performance aerial combat
      maneuvers.
AB  - INTRODUCTION: Neck injuries are common in high performance combat pilots and have
      been attributed to high gravitational forces and the non-neutral head postures
      adopted during aerial combat maneuvers. There is still little known about the
      pathomechanics of these injuries. METHODS: Six Royal Australian Air Force Hawk
      pilots flew a sortie that included combinations of three +Gz levels (1, 3, and 5)
      and four head postures (Neutral, Turn, Extension, and Check-6). Surface
      electromyography from neck and shoulder muscles was recorded in flight. Three
      dimensional measures of head postures adopted in flight were estimated postflight
      with respect to end-range of the cervical spine using an electromagnetic tracking
      device. RESULTS: Mean muscle activation increased significantly with both
      increasing +Gz and non-neutral head postures. Check-6 at +5 Gz (mean activation
      of all muscles = 51% MVIC) elicited significantly greater muscle activation in
      most muscles when compared with Neutral, Extension, and Turn head postures. High
      levels of muscle co-contraction were evident in high acceleration and non-neutral
      head postures. Head kinematics showed Check-6 was closest to end-range in any
      movement plane (86% ROM in rotation) and produced the greatest magnitude of
      rotation in other planes. Turn and Extension showed a large magnitude of rotation
      with reference to end-range in the primary plane of motion but displayed smaller
      rotations in other planes. DISCUSSION: High levels of neck muscle activation and
      co-contraction due to high +Gz and head postures close to end range were evident
      in this study, suggesting the major influence of these factors on the
      pathomechanics of neck injuries in high performance combat pilots.

PMID- 17042251
TI  - Pilot error and its relationship with higher organizational levels: HFACS
      analysis of 523 accidents.
AB  - INTRODUCTION: Based on Reason's model of human error, the Human Factors Analysis
      and Classification System (HFACS) was developed as an analytical framework for
      the investigation of the role of human error in aviation accidents. However,
      there is little empirical work that formally describes numerically the
      relationship between the levels and components in the model (the organizational
      structures, psychological precursors of errors, and actual errors). METHOD: This
      research analyzed 523 accidents in the Republic of China (ROC) Air Force between
      1978 and 2002 through the application of the HFACS framework. RESULTS: The
      results revealed several key relationships between errors at the operational
      level and organizational inadequacies at both the immediately adjacent level
      (preconditions for unsafe acts) and higher levels in the organization (unsafe
      supervision and organizational influences). CONCLUSIONS: This research lends
      support to Reason's model that suggests that active failures are promoted by
      latent conditions in the organization. Fallible decisions in upper command levels
      were found to directly affect supervisory practices, thereby creating
      preconditions for unsafe acts, and hence indirectly impaired performance of
      pilots, leading to accidents. The HFACS framework was proven to be a useful tool
      for guiding accident investigations and developing accident prevention
      strategies.

PMID- 17042252
TI  - General aviation accidents in degraded visibility: a case control study of 72
      accidents.
AB  - BACKGROUND: Accidents in degraded visibility continue to account for a
      disproportionately large number of fatal crashes and fatalities in general
      aviation (GA). However, the relatively small percentage of these crashes annually
      suggests that even a small reduction in the number of crashes can result in a
      large reduction in associated fatalities. OBJECTIVE: This study identified risk
      factors associated with GA accidents that occur in degraded visibility. METHODS:
      Data collected during 72 National Transportation Safety Board investigations of
      GA accidents were compared with data collected from 135 control flights matched
      on weather conditions, location, time, and rules of flight. Study variables
      included pilot demographics, experience, testing and accident histories, and the
      purpose and length of flights. Initial comparisons were conducted using Chi
      square analyses, followed by the development of a logistic regression model.
      RESULTS: Univariate analyses identified significant differences in pilot age at
      accident, age at initial certification, certificate level, instrument rating,
      testing performance, and previous accident involvement. There were also
      significant differences between groups related to aircraft ownership, purpose of
      flight, and intended flight length. The logistic regression revealed significant
      increased risk for pilots initially certified after age 25 [odds ratio (OR) 4.5,
      95% confidence interval (CI) 1.9-10.81, without instrument ratings (OR 4.8, 95%
      CI 1.8-12.8), with prior accidents/incidents (OR 3.1, 95% CI 1.1-8.7), and for
      intended flights longer than 300 nmi (OR 4.6, 95% CI 1.6-13.8). CONCLUSIONS:
      Certain risk factors (e.g., instrument rating) were consistent with previous
      research, while others (e.g., age at certification) raise questions for future
      research.

PMID- 17042253
TI  - Gas nuclei, their origin, and their role in bubble formation.
AB  - Gas bubbles are the primary agent in producing the pathogenic effects of
      decompression sickness. Bubble formation during decompression is not simply the
      consequence of inert gas supersaturation. Numerous experiments indicate that
      bubbles originate as pre-existing gas nuclei. Radii are on the order of 1 microm
      or less. Heterogeneous nucleation processes are involved in generating these gas
      entities. Musculoskeletal activity could be the main promoter of gas nuclei from
      stress-assisted nucleation. The half-life and faculty for nuclei to initiate
      bubble formation during decompression depend on many factors. Oxygen window and
      surface tension are involved in resolving bubbles. Two factors have been proposed
      to stabilize gas nuclei against dissolution: gas nuclei trapped in hydrophobic
      crevices and gas nuclei coated with surface-active molecules such as surfactants.
      Diffusion and surface tension could play an important role in the formation of
      gas nuclei crevices. However, while the concept of in vivo hydrophobic crevices
      remains a theoretical possibility, none have yet been identified in tissues
      and/or in microcapillaries. Moreover, while surfactants seem present in numerous
      tissues and could play a role in gas nuclei stabilization, they could also be
      involved in bubble elimination. The understanding of such mechanisms is of
      primary importance to neutralize nuclei and for modeling bubble growth. Here we
      present in a single document a summary of the original findings and views from
      authors in this field.

PMID- 17042254
TI  - In-flight medical incapacitation and impairment of airline pilots.
AB  - Medical incapacitation in the cockpit is rare, although it is a concern that has
      been the subject of several investigations over the years. With recent heightened
      interest in this problem, it seemed worthwhile to review all relevant scientific
      literature on the topic. Medline, PsychLit, the Aerospace Database, and other
      online databases were searched for studies of pilot in-flight medical
      incapacitation and impairment. The search revealed 13 articles during the years
      from 1968 to 2000. The studies represented several different approaches and were
      divided into five categories as follows: in-flight medical events, career
      termination, simulator data, questionnaires, and epidemiological analysis. The
      articles based on in-flight medical events showed that the leading causes of
      those episodes were myocardial infarctions, cardiac arrhythmias, and epileptic
      seizures. Few of the other types of studies used data from actual in-flight
      medical occurrences, instead relying on indirect measures such as career
      termination due to permanent medical grounding, loss of licensure insurance, or
      general epidemiological data to estimate the frequency of in-flight medical
      events. The reviewed studies provided only limited information on the frequency
      and categories of in-flight medical events and did not include incapacitation
      rates, making meaningful comparison between studies difficult. Future research
      needs to be based on actual in-flight medical events, and should be normalized to
      a useful denominator, such as flight time, to allow for meaningful comparison
      between studies.

PMID- 17042255
TI  - PET scan as an aid for the return of a head-injured aviator to flying duty.
AB  - Head injury is not a rare event in aviators, and poses a difficult dilemma for
      the flight surgeon regarding return to flying duty due to the fear of post
      traumatic epilepsy. Positron emission tomography (PET) is a functional
      neuroimaging modality that provides additional localizing data in epileptic
      patients in the interictal phase. We describe a case of penetrating head trauma
      with no loss of consciousness in a military jet fighter pilot in which the
      magnetic resonance imaging revealed a minimal brain contusion. PET scan was used
      as an additional tool for predicting the epileptogenic potential of this finding,
      thus aiding the decision regarding the return of the aviator to flying duty.

PMID- 17042256
TI  - PET scans and traumatic brain injuries: a brief comment.

PMID- 17042257
TI  - Lunar exploration and the advancement of biomedical research: a physiologist's
      view.
AB  - Over the next few years, it will become apparent just how important lunar
      exploration is to biomedical research and vice versa, and how critical both are
      to the future of human spaceflight. NASA's Project Constellation should put a new
      lunar-capable vehicle into service by 2014 that will rely on proven Space Shuttle
      components and allow four astronauts to spend 7 d on the lunar surface. A modern
      space transportation system opens up a unique opportunity in the space sciences-
      the establishment of a permanent lunar laboratory for the physical and life
      sciences. This commentary presents a rationale for focusing American efforts in
      space on such a Moon base in order to promote understanding of the long-term
      physiological effects of living on a planetary body outside the Van Allen belts.

PMID- 17042258
TI  - Albrecht Ludwig Berblinger--inventor of the spring prosthesis and hang-glider
      (1811).
AB  - Albrecht Ludwig Berblinger (1770-1829), known as the "Flying Tailor of Ulm",
      started with flight experiments in Ulm, Germany, in the early 19th century. He
      gained experience in downhill gliding with a maneuverable airworthy semi-rigid
      hang-glider and then attempted to cross the Danube River at Ulm's Eagle's Bastion
      on the 31st of May 1811. The tricky local winds caused him to crash and he was
      rescued by fishermen, making him the first survivor of a water immersion accident
      of a heavier-than-air manned "flight machine". Though he failed in his attempt to
      be the first man to fly, Berblinger can be regarded as one of the significant
      aviation pioneers who applied the "heavier than air" principle and paved the way
      for the more effective glide-flights of Otto Lilienthal (1891) and the Wright
      Brothers (1902). Less known are Berblinger's significant contributions to the
      construction of artificial limbs for medical use, as well as the spring
      application in aviation. His invention of a special mechanical joint was also
      used for the juncture of the wings of his "flying machine". Because of his
      worthwhile contributions to medicine and flight, in 1993 the German Academy of
      Aviation Medicine named an annual award for young scientists in the field of
      aerospace medicine in his honor.

PMID- 17042259
TI  - Posner-Schlossman syndrome and medical certification.
AB  - Posner-Schlossman syndrome is a rare eye condition involving mild anterior
      chamber inflammation and extreme intermittent intraocular pressure elevations.
      Symptoms are mild and not incapacitating, but aviators need proper diagnosis and
      treatment to ensure that visual acuity and visual fields are not affected.

PMID- 17042260
TI  - You're the flight surgeon. Restless legs syndrome.

PMID- 17042261
TI  - Cardiovascular tech trends.

PMID- 17042262
TI  - [PH-sensitive cationic lipopeptides for the design of drug-delivery systems].
AB  - Lipopeptides on the basis of L-glutamic acid and glutamine di- and monoesters
      with aliphatic alcohols of various lengths that contain L-arginine, L-ornithine,
      and L-lysine were synthesized. The behavior of these amphiphiles in aqueous
      medium was shown to depend on their structure.

PMID- 17042263
TI  - [Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro].
AB  - Luliberin analogues modified at the N-terminus were synthesized to search for
      drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A
      synthetic scheme effective in the preparation of analogues containing fatty acid
      residues was proposed. The cytotoxic effect of the peptides was studied on a
      number of cell lines of human tumors in vitro. The dependence of the antitumor
      effect on the length of peptide chain, amino acid sequence, and structure of the
      N-terminal group was demonstrated. Modification with palmitic acid was found to
      result in highly active compounds in the case of analogues containing more than
      ten aa, whereas modifications with lauric, caproic, or trimethylacetic acid led
      to compounds with significantly lower activities. Analogues of luliberin
      containing a palmitic acid residue and effectively inhibiting the growth of tumor
      cells in vitro were synthesized.

PMID- 17042264
TI  - [Spontaneous and promoted association of linear oligoglycines].
AB  - Linear oligoglycines of various lengths bearing a carboxyl or an amide group at
      their C-termini and also their poly(acrylamide) conjugates were synthesized. No
      self-assembly into supramolecular structures was observed for free oligoglycines
      H-(Gly)m-OH(m = 3-5). At the same time, oligoglycylamides H-(Gly)m-NH2 (m = 3-5)
      demonstrated ability for both self-assembly in aqueous solution and assembly
      promoted by an additional interaction with surface. In the case of polymer-bound
      oligoglycines (and their amides), no intramolecular clustering of peptide chains,
      as expected, was observed. This means that the presence of several oligoglycine
      chains bound to each other in one center is not a necessary prerequisite for
      polyglycine II-type association.

PMID- 17042266
TI  - [Stabilization of glucoso-6-phosphate dehydrogenase by its substrate and cofactor
      in an ultrasonic field].
AB  - The inactivation kinetics of glucoso-6-phosphate dehydrogenase (GPDH) and its
      complexes with glucoso-6-phosphate and NADP+ was characterized in aqueous
      solutions at 36-47 degrees C under treatment with low frequency (27 kHz, 60
      W/cm2) and high frequency ultrasound (880 kHz, 1 W/cm2). To this end, we measured
      three effective first-order inactivation rate constants: thermal k(in)* , total
      (thermal and ultrasonic) kin, and ultrasonic kin (US). The values of the
      constants were found to be higher for the free enzyme than for its complexes GP
      DH-GP and GPDH-NADP+ at all temperatures, which confirms the enzyme stabilization
      by its substrate and cofactor under both thermal and ultrasonic inactivation.
      Effective values of the activation energies (Ea) were determined and the
      preexponential factors of the rate constants and thermodynamic activation
      parameters of inactivation processes (deltaH*, deltaS*, and deltaG*) were
      calculated from the temperature dependences of the inactivation rate constants of
      GPDH and its complexes. The sonication of aqueous solutions of free GPDH and its
      complexes was accompanied by a reduction of Ea and deltaH* values in comparison
      with the corresponding values for thermal inactivation. The Ea, deltaH*, and
      deltaS* inactivation values for GPDH are lower than the corresponding values for
      its complexes. A linear dependence between the growth of the deltaH* and deltaS*
      values was observed for all the inactivation processes for free GPDH and its
      complexes.

PMID- 17042265
TI  - [Stress-protective effect of the synthetic ACTH-like peptide leucocorticotropin].
AB  - We found that the tritium-labeled synthetic ACTH-like octapeptide
      leucocorticotropin corresponding to the 81-88 sequence of the precursor of human
      interleukin-1alpha ([3H]GKVLKKRR) is bound by the ACTH receptor of rat adrenal
      cortex with a high affinity and specificity (Kd 2.2 +/- 0.1 nM). This peptide was
      shown to exert no effect on the adenylate cyclase activity of the membranes of
      rat adrenal cortex in the concentration range from 1 to 1000 nM.
      Leucocorticotropin administration three times at doses of 10-20 microg/animal did
      not change the level of hydroxycorticosteroids (11-HOCS) in the rat adrenal
      glands in the absence of temperature action. At the same time, the peptide
      abolishes (at a dose of 20 microg/animal, three times) or significantly decreases
      (at a dose of 10 microg/animal, three times) the dramatic increase in the 11-HOCS
      content in the adrenal glands occurring in the case of cold or heat shock. Thus,
      leucocorticotropin normalizes the 11-HOCS level in the rat adrenal cortex during
      stress. The stress-protective effect of the peptide is mediated through the ACTH
      receptor.

PMID- 17042267
TI  - [Compaction of single supercoiled DNA molecules adsorbed onto amino mica].
AB  - A model of possible conformational transitions of supercoiled DNA in vitro in the
      absence of proteins under the conditions of increasing degree of compaction was
      developed. A 3993-bp pGEMEX supercoiled DNA immobilized on various substrates
      (freshly cleaved mica, standard amino mica, and modified amino mica with a
      hydrophobicity higher than that of standard amino mica) was visualized by atomic
      force microscopy in air. On the modified amino mica, which has an increased
      density of surface positive charges, single molecules with an extremely high
      degree of compaction were visualized in addition to plectonemic DNA molecules. As
      the degree of DNA supercoiling increased, the length of the first-order
      superhelical axis of molecules decreased from 570 to 370 nm, followed by the
      formation of second- and third-order superhelical axes about 280 and 140 nm long,
      respectively. The compaction of molecules ends with the formation of minitoroids
      about 50 nm in diameter and molecules of spherical shape. It was shown that the
      compaction of single supercoiled DNA molecules immobilized on amino mica to the
      level of minitoroids and spheroids is due to the shielding of mutually repulsing
      negatively charged phosphate groups of DNA by positively charged amino groups of
      the amino mica, which has a high charge density of its surface.

PMID- 17042268
TI  - [Functionalized nanocomposite coating of a glass surface for oligonucleotide
      immobilization].
AB  - A new type of coating for manufacturing DNA chips was constructed of the basis of
      an organic-inorganic nanocomposite based on the polyvinylbutyral
      tetraethoxysilane copolymer. The organosilicon composite was functionalized by
      introduction of ethanolamine vinyl ether copolymers, which contain amino groups
      and anchor vinyloxide units capable of reacting with silanol groups of the
      nanocomposite. The resulting coatings form a film on glass slides with a high
      surface density of amino groups (up to 700 groups/nm2) suitable for three
      dimensional immobilization of oligonucleotides. The use of bifunctional reagents
      (e.g., phenylene diisothiocyanate) for the attachment of oligonucleotides bearing
      amino linkers to the amino-containing surface provides an immobilization density
      of 0.5-1.6 pmol/mm2. Immobilization with a higher density (10-12 pmol/mm2) was
      achieved for attachment to amino-containing glass slides upon the use of
      oligonucleotides containing selectively activated terminal phosphate groups. The
      activation of oligonucleotides was carried out with the triphenylphosphine
      dithiodipyridine pair in the presence of dimethylaminopyridine N-oxide. The
      resulting DNA chips were shown to be useful in principle for DNA detection.

PMID- 17042269
TI  - [Glycosylation of 5-Phenyl-1,3,4-oxadiazole-2-thiol with alpha-D-glucopyranosyl
      chloride under phase transfer conditions].
AB  - 5-Phenyl-1,3,4-oxadiazole-2-thiol is glycosylated easily and in high yields with
      2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosyl chloride in the
      presence of catalytic amounts of aliphatic and aromatic crown ethers under phase
      transfer (solid-organic solvent) conditions. The reaction rate and the ratio of
      the resulting N- and S-regioisomers depend on the catalyst nature.

PMID- 17042270
TI  - [Chemical modification of heparin].
AB  - Heparin was modified at carboxyl groups by reaction with several
      pharmacologically important amino-containing compounds in aqueous medium in the
      presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. In dependence on the
      nature of the amine and the ratio of reagents, conjugates containing 36-100%
      amide and 0-25% isoureidocarbonyl groups were synthesized. Isoureidoarylamide
      groups are present, along with amide moieties, in the products of heparin
      modification by hydroxyl-containing aromatic amines. The conjugate of heparin
      with p-aminobenzoic acid contained oligomeric arylamide.

PMID- 17042271
TI  - [Identification and structural analysis of a glycophospholipid component from the
      venom of ant Paraponera clavata].
AB  - The venom of South American ant Paraponera clavata and its low-molecular-mass
      fraction were shown to possess insectotoxic and pore-forming activities. A number
      of glycophospholipid components were isolated from this ant venom by means of gel
      filtration and reversed-phase chromatography. Some of the compounds cause
      conductivity fluctuations in lipid bilayer membranes within the ranges 3-25 pS
      and 200-400 pS at concentrations of 10(-6) to 10(-7) M. N-Acetylglucosamine, a
      fatty acid, and phosphoric acid residues were found in their structures. A full
      structure, 3-myristoyl-2-acetamido-2-deoxy-alpha-D-glucopyranosyl phosphate, was
      elucidated for one of the compounds by the use of 1H, 13C, and 31P NMR
      spectroscopy and mass spectrometry.

PMID- 17042272
TI  - [An unusual lipid A from a marine bacterium Chryseobacterium scophtalmum CIP
      104199T].
AB  - The hydrolysis of defatted cells of the marine bacterium Chryseobacterium
      scophtalmum CIP 104199T with 10% acetic acid (3 h, 100 degrees C) led to an
      unusual lipid A (LA) (yield 0.6%), obtained for the first time. Using chemical
      analysis, FAB MS, and NMR spectroscopy, it was shown to be D-glucosamine 1
      phosphate acylated with (R)-3-hydroxy-15-methylhexadecanoic and (R)-3-hydroxy-13
      methyltetradecanoic acids at the C2 and C3 atoms, respectively. It is similar to
      the monosaccharide biosynthetic precursor of lipopolysaccharide (LPS), so-called
      lipid X (LX). Unlike LX, LA can be isolated by the treatment of bacteria with
      organic solvents only after the preliminary acidic hydrolysis of the cells, which
      suggests that LA might be strongly, probably chemically, linked to other
      components of the outer membrane. However, LPS cannot be such a component,
      because extraction with phenol-water or phenol-chloroform-petroleum ether
      mixtures in high yields (5.34% and 0.5%, respectively) leads to preparations that
      do not contain 3-deoxy-D-manno-oct-2-ulopyranosonic acid, 3-hydroxyalkanoic
      acids, or LA.

PMID- 17042273
TI  - [Synthesis of thio- and selenophospholipids from 2,2,5,5
      tetra(hydroxymethyl)cyclopentanone].
AB  - New phospholipids, thio- and selenoanalogues of phosphatidic acids, were
      synthesized on the basis of 2,2,5,5-tetra(hydroxymethyl)cyclopentanone. The
      starting tetraol monoketal was phosphorylated with amidophosphorous acid
      chlorides to protected polyol amidophosphites, which were further sulfurized or
      selenized to phosphoacetals. These were directly acylated with fatty acid
      chlorides to thio- and selenoanalogues of phospholipids.

PMID- 17042274
TI  - [Delta5-7-Ketosterols with modified side chain: the synthesis and the effects on
      viability and cholesterol biosynthesis in Hep G2 cells].
AB  - (22E)-3beta-Hydroxysitosta-5,22-dien-7-one, (22R, 23R)-3beta,22,23
      trihydroxysitost-5-en-7-one, and (22R, 23R)-3beta-hydroxy-22,23
      isopropylidenedioxysitost-5-en-7-one were synthesized. The cytotoxicity and
      effects on cholesterol biosynthesis of the resulting 7-ketosterols, 7
      ketocholesterol, and (22S,23S)-3beta-hydroxy-22,23-oxidositost-5-en-7-one were
      studied in hepatoblastoma Hep G2 cells.

PMID- 17042275
TI  - [Synthesis of ethriolophospholipids of acetal type].
AB  - New analogues of acetal-type phospholipids were obtained on the basis of ethriol
      (2-hydroxymethyl-2-ethyl-1,3-propanediol). The starting triol originally was
      condensed with decanal or dodecanal to form acetals, which were then
      phosphorylated with tetraethyldiamidophosphorous acid chloride. The
      amidophosphites were further oxidized with iodosobenzene or sulfurized to the
      corresponding acetal-type phospholipids and their thio analogues.

PMID- 17042276
TI  - [The symbiotic microflora associated with the tegument of proteocephalidean
      cestodes and the intestines of their fish hosts].
AB  - The indigenous symbiotic microflora associated with the tegument of
      proteocephalidean cestodes and the intestines of their fish hosts has been
      investigated in morphological and ecological aspects. The indigenous microflora
      associated with the cestode tegument consists of the nannobacteria population,
      which was present obligatorily on the surface of tegument, and the "deep
      microflora". The deep microflora associates with some few species of parasites
      only. Each individual host-parasite micro-biocenosis includes specific indigenous
      symbiotic microorganisms, with the differing microfloras of host intestine and
      parasite. Physiology, biochemistry and/or diet of hosts apparently influence on
      the symbiotic microflora's structure of parasites. The least bacteria abundance
      and diversity of their morphotypes were observed in the parasites from baby
      fishes. The diversity and abundance of bacteria were increased with the fish host
      ageing and the formation of the definitive structure of its intestine. It is an
      evidence of the gradual invading of the intestinal parasites (cestodes) tegument
      by bacterial cells. The invading is realized on the base of the microflora that
      was present in the food of fish host. The symbiotic microflora has specific
      morphological features, can regulate the homeostasis of the cestodes and fish
      hosts and also can maintain equilibrium of alimentary and immune interrelations
      in the host-parasite system.

PMID- 17042277
TI  - [Taxonomic diversity of parasites from agnathans and fishes in the Volga basin.
      II. Parasitic Coelenterata and Monogenea].
AB  - A checklist of the Monogeneans and Coelenterates parasitizing fishes in the Volga
      River basin is given. The list of hosts with the data on their occurrence in
      different areas of the Volga River basin is provided for each parasite species.
      The data on the parasites from 46 fish species are presented. The checklist
      includes 139 species and 6 taxa of subspecific rank. 9 species (Dactylogyrus
      aristichthys, D. ctenopharyngodonis, D. hypophthalmichthys, D. lamellatus, D.
      nobilis, D. suchengtaii, Pseudodactylogyrus bini, P. microrchis, and Eudiplozoon
      nipponicum) were introduced into the Volga River basin accidentally together with
      the Far Eastern fish species during the process of their naturalization.

PMID- 17042278
TI  - [Dracunculoid nematodes (Spirurida: Dracunculoidea) of fishes from the Volga
      River delta].
AB  - Faunistic and some morphological data, as well as nomenclature notes on
      dracunculoid nematodes parasitising fishes in the Volga River delta, are
      presented. The author replaced a preoccupied generic name Molnaria Moravec, 1968
      (Skrjabillanidae) by the new name Kalmanmolnaria nom. nov. The validity of
      Philometroides lusii (Vismanis, 1962) comb. nov. as a senior objective synonym of
      Philometroides lusiana (Vismanis, 1967) Ivaschkin et al., 1971 is restored.

PMID- 17042279
TI  - [Morphofunctional changes in the midgut of the Ixodes females (Acari: Ixodidae)
      during the immunizing feedings].
AB  - The changes of the midgut in the females of the tick species Ixodes persulcatus
      and I. ricinus during the second and third immunizing feeding on rabbits were
      studied by the histological technics. The alternation of one generation of the
      digestive cells of nymphal stage and two generations of the digestive cells of
      adult stage was observed. The generation of secretory cells is absent. The tick
      completes feeding and drop off when the last generation of the digestive cells is
      on the initial activity stages. The amount of the blood consumed is not enough
      for the rhythmical functioning of the midgut. The feeding of tick is broken on
      the second phase and full satiation does not take place. It is apparently an
      effect of the interruption of the blood entrance into the midgut cavity of
      feeding tick as a probable result of anti-ticks resistance of unnatural hosts.

PMID- 17042280
TI  - [Spatial and temporal structure of the infectious diseases incidence in the
      population of the south of the Russian Far East: system approach].
AB  - New conception of the anthropo-parasitic system has been elaborated. Spatial and
      temporal structure of the infections diseases incidence in the Primorye Territory
      has been analysed on the base of this conception.

PMID- 17042281
TI  - [The longevity of the tick Ixodes ricinus (Acari: Ixodidae) in Central Russia].
AB  - The longevity of the tick Ixodes ricinus has been studied on 27 samples from a
      wild population of the Moscow Region. Ticks were kept in small cages and glass
      tubes under conditions close to natural. About 2/3 of the specimens collected in
      spring survived till the next spring and later died out gradually during the
      second season of their activity. Very few specimens reached the beginning of the
      third winter in their life, but apparently none of them survived the end of the
      winter. The life span of males was the same as that of females. No mass
      activation of adult ticks was recorded in the autumn of the year of their
      molting. It seems that the rise of the autumnal density of adult ticks depends
      mainly on the increased activity of the females which molted from nymphs last
      year.

PMID- 17042282
TI  - [The abundance and distribution of the Ixodes persulcatus (Acari: Ixodidae) near
      its northern spreading limit in the Ural Mountains].
AB  - A count of the tick species Ixodes persulcatus Schulze, 1930 was carried out in
      the "Denezhkin Kamen" Nature Reserve and adjacent territories (the Severoural'sk
      and Ivdel' Districts of the Sverdlovsk Region, the Northern Urals geographical
      province) in the 2005. The abundance and distribution of unengorged adults has
      been evaluated on an area of 22.5 square kilometers (N 60 degrees 27'-60 degrees
      30' E 059 degrees 38'-059 degrees 42'). The area includes proportionally main
      landscape and vegetation elements of the region studied, from mountain analogues
      of the middle and northern taiga up to tundra. One tick species, I. persulcatus,
      has been collected by flagging with the abundance from 0.4 up to 6.8 (average 1.6
      +/- 0.9) specimens per flag-hour. The observed values of abundance are classified
      into three classes (I - ticks are absent, II - 1-2 specimens, and III - 3-7
      specimens per flag-hour). The class I amounts 20, II - 75, and III - 5% of the
      area examined. It has been revealed by the expert evaluation of the 2003-2004 and
      counts of the 2005 that ticks occur stably in the Northern Ural, reaching N 61
      degrees and 400 m above sea level. The level of the species abundance remained
      constant till the middle of summer. In this period the activity of ticks
      dependent on the weather optimum only.

PMID- 17042283
TI  - EMRs and quality improvement in patient care.

PMID- 17042284
TI  - How to choose an electronic medical record.
AB  - I chose a Windows-based file system over a server-based system with a proprietary
      database, or a web-based system which has both a proprietary database and which
      also required a full time Internet connection. My reasoning was that I found it
      uncomplicated. I was familiar with the Windows interface and it required little
      effort to enter my existing data and was simple to operate the system. If one
      laptop crashes, my other computers still work. I don't fear failure of an
      Internet connection source, a modem or a server, power surges or other possible
      single points of failure that might prevent my patient care. I can incorporate
      all document types, I can update jump drives with any needed medical information.
      I can share information instantly with other systems. I can store my own data in
      a flexible and open format. I have no maintenance contract and I can make changes
      in my system or can even change vendors at any time. Last but certainly not
      least, I do not need a highly trained technical staff to operate or maintain our
      system.

PMID- 17042285
TI  - Electronic medical records delivers quality and efficiency to small practice.

PMID- 17042286
TI  - Pediatric practice selects program designed by pediatrician.

PMID- 17042287
TI  - Embracing change leads to improving patient care.

PMID- 17042288
TI  - Using electronic medical records in the 21st century.

PMID- 17042290
TI  - Medicine weathers challenging legislative session.

PMID- 17042289
TI  - EMR decision time: your Rx for success.

PMID- 17042291
TI  - CDC's Advisory Committee recommends human papillomavirus virus vaccination.

PMID- 17042292
TI  - Legal implications of the electronic medical record in Georgia.

PMID- 17042293
TI  - Physician be wary: the status of employment restrictive covenants in Georgia.

PMID- 17042294
TI  - The 15th hole.

PMID- 17042295
TI  - Hard work.

PMID- 17042296
TI  - How on earth did this happen?

PMID- 17042297
TI  - Nursing home medical director: revised CMS guidelines emphasize leadership.

PMID- 17042298
TI  - Now hiring! Arkansas, like the nation, faces imminent health care worker
      shortages.

PMID- 17042299
TI  - Pericarditis: guidelines and management.

PMID- 17042300
TI  - Cardiac transplantation at Arkansas Children's Hospital.
AB  - Cardiac transplantation in children has evolved over the past 20 years. In 1990
      Arkansas Children's Hospital (ACH) developed a Cardiac Transplant Program as part
      of its tertiary care of patients with congenital and acquired heart disease. The
      program evolved into a regional pediatric referral program and is now one of the
      busiest in the United States. "Bridging" to transplant increased the number of
      patients surviving long enough to receive a donor heart. This article reviews the
      historical perspective of pediatric cardiac transplant along with the development
      and current state of the program at Arkansas Children's Hospital.

PMID- 17042301
TI  - Now and then: the progress of care.

PMID- 17042302
TI  - Oxygen administration: is practice based on evidence?
AB  - An audit of oxygen administration to children in the paediatric unit of a
      district general hospital was carried out following the introduction of new
      guidelines. The aim of the audit was to review oxygen administration practices
      against the guidance but also to gather information concerning patients,
      diagnoses, prescription practices and delivery devices. The notes of 36 infants
      and children admitted during a two week (winter) period who received oxygen were
      retrospectively reviewed for the audit. The standards for monitoring the amount
      of oxygen delivered and oxygenation were found to be high but the prescribing of
      oxygen was varied. The most common diagnosis of children receiving oxygen was
      bronchiolitis, and the device used to deliver oxygen most frequently was nasal
      cannula. Few headboxes were used and experienced team members noted this as a
      marked change in practice. A further examination of the evidence on the use of
      nasal cannulae for oxygen delivery in the younger age group led to new practice
      recommendations.

PMID- 17042303
TI  - Sex education in school: young people's views.
AB  - The aims of this study were to explore adolescents' levels of knowledge on sexual
      health issues and their views on the sex education they receive as part of their
      compulsory education. Twenty students from two schools completed a short
      questionnaire and participated in a focus group discussion. The students had an
      excellent level of knowledge about sexual health issues, which contradicts
      Government views that ignorance is the key to adolescents' sexual health concerns
      (Social Exclusion Unit 1999). Participants felt their sex education was 'too
      little, too late' and that it should be taught by someone other than a teacher.
      Sex education should be introduced earlier in the curriculum as well as finding
      an acceptable 'teacher' if adolescent sexual health is to improve.

PMID- 17042304
TI  - Breast feeding and society.
AB  - Britain has the lowest breastfeeding rate of all countries in Europe; it is no
      longer the cultural norm in our society. Breastfeeding rates are affected by
      public attitude. This state of affairs is partly because of society's views on
      breastfeeding mothers, even though breastfeeding is known to be the optimum
      method of infant feeding for the baby, family and society. Common themes in the
      literature and websites are the economic advantages of breastfeeding, the public
      health benefits and the social construct of breastfeeding. Paediatric nurses have
      an important role in supporting breastfeeding mothers so that they are able to
      continue breastfeeding.

PMID- 17042305
TI  - Outreach: making a difference in family life.

PMID- 17042306
TI  - Improving links between CAMHS and primary care.
AB  - Only a small percentage of children and young people with mental health problems
      reach child and adolescent mental health services (CAMHS) (Young Minds 2003).
      Government policy, voluntary organisation reports and research all support the
      need for improved links and open communication between health services in order
      to address the mental health needs of children and young people.

PMID- 17042307
TI  - Wound management.

PMID- 17042308
TI  - Inhaled nitrous oxide during painful procedures: a satisfaction survey.
AB  - Children with cystic fibrosis (CF) undergo repeated invasive medical procedures.
      This article summarises a survey of the use of nitrous oxide to minimise the
      psychological trauma and pain that was undertaken within the paediatric unit of a
      district general hospital (Williams et al 2004). Pain levels pre and post
      procedure, whether the treatment was effective, any adverse effects and comments
      by children and carers were recorded. Nitrous oxide was safe and effective in
      reducing pain, trauma and 'needle phobia'. It is now being offered to other
      children in the management of procedural pain.

PMID- 17042309
TI  - Negotiation of care by children's nurses: lessons from research.
AB  - Parental participation and role negotiation are central elements in family
      centred care, but research suggests that such negotiation tends to be ad hoc,
      depending on the relationships developing between the family and health
      professionals. Lack of effective communication, professional expectations and
      issues of power and control often prevent open and mutual negotiation between
      families and health professionals, especially nurses. This article summarises key
      lessons from a critical review of relevant research literature (Corlett and
      Twycross 2006) which suggests that nursing staff often control parental
      participation leaving parents feeling disempowered and deskilled. Poor
      communication and lack of information sharing exacerbate the situation. Where
      parents do not comply with nurses' expectations conflict can arise, resulting in
      more anxiety for already stressed parents. Current health policy requires that
      health workers listen to children and their families, to actively involve them in
      the decision-making process and to plan care around their needs and wishes.
      Nurses need to be aware of the way they interact with parents and the control
      they may unwittingly exert. A greater emphasis on communication, interpersonal
      and negotiation skills within nurse education is also needed.

PMID- 17042310
TI  - Developing rigour in observation of the sick child: Part 1.
AB  - This is the first of a five part series focused on the continuing professional
      development of rigour in observation of the sick child. Part 1 provides an in
      depth analysis of basic principles underpinning observation generally. Parts 2 to
      5 will provide in-depth analyses of specific nursing observations.

PMID- 17042311
TI  - A picture of the United Kingdom using the National Statistics Socio-economic
      classification.
AB  - This article describes the socio-economic characteristics of working age people
      in the United Kingdom in 2005 based on the National Statistics Socio-economic
      Classification. The population is described by NS-SEC and gender, age-group,
      region or household type.

PMID- 17042312
TI  - Introducing the area classification of output areas.
AB  - This article provides a brief introduction to the Area Classification of Output
      Areas. The classification uses data from the 2001 Census to group the 223,060
      output areas into groups of similarity based on their census attributes. The
      classification is freely available as a 'National Statistic' via the National
      Statistics website.

PMID- 17042313
TI  - Methodology used for producing ONS's small area population estimates.
AB  - The Office for National Statistics (ONS) has set up a project to investigate the
      feasibility of producing postcensal small area population estimates on a
      nationally consistent basis for England and Wales. Following on from earlier
      investigations to identify potential data sources and methods, ward and Super
      Output Area population estimates have been released as 'experimental statistics'.
      This article covers the methodology used to produce these estimates, feedback
      from user consultation with the initial estimates released at ward level, summary
      statistics on the population estimates for mid-2001 to mid-2003, and future
      developments for small area population estimates.

PMID- 17042314
TI  - An international comparative study on the use of the Cohort Component Method for
      estimating national populations.
AB  - This comparative study explores the use of the Cohort Component Method (CCM) to
      produce national level population estimates. This method is used annually to
      calculate mid-year population estimates for England and Wales by the Office for
      National Statistics (ONS). Initially the article considers recent population
      change in England and Wales, with particular emphasis on the growing importance
      and challenges faced by migration estimation. Comparisons are then made between
      how population estimates are produced in England and Wales and other countries,
      with a particular focus on differences in the way the CCM is applied. Recent
      changes in methods used to estimate population are then reviewed along with a
      discussion of alternative approaches such as those described in academic
      literature.

PMID- 17042315
TI  - Report: Joint ESRC/ONS/BSPS public policy seminar series on the implications of
      demograhic change.

PMID- 17042316
TI  - Living the legacy of 'Mother Seacole'.

PMID- 17042318
TI  - An informative day.

PMID- 17042317
TI  - The NHS pension scheme review--existing members.

PMID- 17042319
TI  - The contribution of patients and the public to the NICE guideline.

PMID- 17042320
TI  - A question of influence.

PMID- 17042321
TI  - Medicines in maternal and neonatal care.

PMID- 17042322
TI  - Consultation on NMC changes.

PMID- 17042323
TI  - A time of independence.

PMID- 17042324
TI  - A double act: implementing the National Service Framework.

PMID- 17042325
TI  - Awareness of von Willebrand's.

PMID- 17042326
TI  - Did the recent media coverage of the healthcare commission report accurately
      portray to the public, the profession and the role of the midwife?

PMID- 17042327
TI  - Synergistic combination effect of cidofovir and idoxuridine on vaccinia virus
      replication.
AB  - In view of the potential menace of a terrorism attack with smallpox virus, an
      intensive search of chemotherapeutic agents active against orthopoxviruses is
      underway. We comparatively studied the antiviral activity of cidofovir (CDV) and
      idoxuridine (IUdR) against two vaccinia virus (VV) strains, Bratislava and RIIPD,
      in cell cultures of chick embryo fibroblasts (CEF). The investigations were
      carried out according to cytopathic effect (CPE) inhibition assay protocols. To
      determine the cytotoxicity of the compounds, maximal tolerated concentration
      (MTC) was calculated in CEF cell monolayers and 50% cell growth inhibitory
      concentration (CGIC50) was calculated in growing cell cultures. It was found that
      the antiviral effects were strongly dependent on virus inoculum size. There were
      no marked differences in the susceptibility to CDV and IUdR between the two VV
      strains. The individual half maximal inhibitory concentration (IC50) for CDV
      varied from 7.1-8.5 microM at 10/100 virus 50% infectious dose (ID50) to 13.6
      26.5 microM at 10,000 ID50. The CDV selectivity index was also virus dose
      dependent with MTC/IC50 and CGIC50/IC50 values ranging between 37.8-141.4 and
      33.3-124.6, respectively. For IUdR, IC50 ranged from 0.58 to 0.85 microM, but the
      selectivity index for monolayer CEF and growing cell cultures produced
      substantial different results with MTC/IC50 and CGIC50/IC50 values between 117.7
      172.4 and 20.4-33.3, respectively. The combination effects of CDV and IUdR
      against VV Bratislava strain in the CPE inhibition test were also determined. The
      test design of both combination antiviral effect and combined cytotoxicity
      followed a three-dimensional model. The combined effect of CDV and IUdR on VV
      replication in monolayer CEF cultures was characterized as a markedly synergistic
      one. In contrast, CDV and IUdR together reduced cytotoxicity in both monolayer
      and growing CEF cells.

PMID- 17042328
TI  - Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors:
      synthesis, biological evaluation and binding mode studies of new derivatives at
      indole-2-carboxamide.
AB  - New non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active
      against the commonly occurring mutations of HIV are urgently needed for the
      treatment of AIDS. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS)
      family, which are endowed with high antiviral potency against HIV-1 wt (wild
      type), and the Y181C and K103N-Y181C drug resistant mutant strains. Several new
      compounds were highly active in lymphocytes infected with primary isolates
      carrying the K103N-V1081-M184V and L1001-V1081 mutations. The design of new IASs
      was based on three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies and docking simulations. A cross-docking study was also undertaken
      to gain some insights in to the binding mode of the newly synthesized IASs in the
      wt and mutated isoforms of reverse transcriptase.

PMID- 17042329
TI  - Inhibition of hepatitis C replicon RNA synthesis by beta-D-2'-deoxy-2'-fluoro-2'
      C-methylcytidine: a specific inhibitor of hepatitis C virus replication.
AB  - beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is a cytidine analogue
      with potent and selective anti-hepatitis C virus (HCV) activity in the subgenomic
      HCV replicon assay, 90% effective concentration (EC90)=4.6 +/- 2.0 microM. The
      spectrum of activity and cytotoxicity profile of PSI-6130 was evaluated against a
      diverse panel of viruses and cell types, and against two additional HCV-1b
      replicons. The S282T mutation, which confers resistance to 2'-C-methyl adenosine
      and other 2'-methylated nucleosides, showed only a 6.5-fold increase in EC90.
      When assayed for activity against bovine diarrhoea virus (BVDV), which is
      typically used as a surrogate assay to identify compounds active against HCV, PSI
      6130 showed no anti-BVDV activity. Weak antiviral activity was noted against
      other flaviviruses, including West Nile virus, Dengue type 2, and yellow fever
      virus. These results indicate that PSI-6130 is a specific inhibitor of HCV. PSI
      6130 showed little or no cytotoxicity against various cell types, including human
      peripheral blood mononuclear and human bone marrow progenitor cells. No
      mitochondrial toxicity was observed with PSI-6130. The reduced activity against
      the RdRp S282T mutant suggests that PSI-6130 is an inhibitor of replicon RNA
      synthesis. Finally, the no-effect dose for mice treated intraperitoneally with
      PSI-6130 for six consecutive days was > or =100 mg/kg per day.

PMID- 17042330
TI  - Synthesis and antiviral evaluation of alkoxyalkyl esters of
      phosphonopropoxymethyl-guanine and phosphonopropoxymethyl-diaminopurine.
AB  - Phosphonopropoxymethyl-guanine is the methylene phosphonate analogue of
      acyclovir. Although not highly active against HSV, 4-38 microM of
      phosphonopropoxymethyl-guanine has been reported to be active against human and
      murine cytomegalovirus. Recently we found that cidofovir, when esterified with
      alkoxyalkyl moieties, showed greatly increased antiviral activity against
      cytomegalovirus, herpes simplex virus and orthopoxviruses, in vitro. The
      alkoxyalkyl esters of cidofovir are orally active in murine models of human and
      murine cytomegalovirus and orthopoxviruses in vivo. To see if the antiviral
      activity of phosphonopropoxymethyl-guanine, phosphonopropoxymethyl-diaminopurine
      and phosphonopropoxymethyl-N6-cyclopropyl-diaminopurine could be increased by
      this approach, we synthesized their hexadecyloxypropyl- and octadecyloxyethyl-
      esters and evaluated antiviral activity and cytotoxicity in cells infected with
      HSV-1 and HCMV, in vitro. Marked increases in antiviral activity were noted in
      the alkoxyalkyl esters of phosphonopropoxymethyl-guanine. Alkoxyalkyl esters of
      diaminopurine and N6-cyclopropyl-diaminopurine showed slight increases in
      activity against HSV-1 and marked increases in activity against HCMV. The results
      suggest that esterification with alkoxyalkyl moieties may be a generally useful
      way to increase antiviral activity of nucleoside phosphonates.

PMID- 17042331
TI  - Anti-herpes simplex virus activities of two novel disulphated cyclitols.
AB  - By screening a library of sulphated compounds of low molecular weight, we have
      found that several cyclitol derivatives, each modified with two sulphate groups
      in addition to pyrrole and various aromatic moieties, inhibited infectivity of
      herpes simplex virus (HSV) at concentrations approximately 100 times lower than
      those toxic for cultured cells. These disulphated cyclitols interfered with HSV-1
      attachment to cells, and efficiently reduced the cell-to-cell spread of the
      virus. This effect is most likely due to their low molecular weight and
      associated with the compounds' capability to access the narrow intercellular
      spaces. Furthermore, these disulphated cyclitols also inactivated infectivity of
      HSV. However, the virus-inactivating activities of these compounds were to some
      extent diminished in the presence of human cervical secretions or other protein
      rich solutions suggesting that disulphated cyclitols may have some features of
      surfactant-type virucides. In conclusion, this new class of anti-HSV compounds
      offers potential for further development.

PMID- 17042332
TI  - Short communication inhibitory activity of 4-[(1,2-dihydro-2-oxo-3H-indol-3
      ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl) benzenesulphonamide and its
      derivatives against orthopoxvirus replication in vitro.
AB  - 4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl)
      benzenesulphonamide and its derivatives were tested in vitro for antiviral
      activity against vaccinia and cowpox virus replication in human foreskin
      fibroblast (HFF) cells, and their activity was compared with cidofovir (CDV).
      Among the tested compounds, 4-[(5-methyl-1,2-dihydro-2-oxo-3-H-indol-3
      ylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl)benzene-sulphonamide was the most
      active against vaccinia virus, with a 50% effective concentration (EC50) value of
      18 microM and 4-[(N-acetyl-1,2-dihydro-2-oxo-3-H-indol-3-ylidene)amino]-N-(4,6
      dimethylpyrimidin-2-yl) benzenesulphonamide was the most active against cowpox
      virus (EC50=33 microM). Cidofovir was found to have an EC50 of 20 microM and 32
      microM against vaccinia and cowpox virus, respectively. Most of the tested
      compounds were non-cytotoxic (>300 microM) in HFF cells as determined by a
      neutral red uptake assay. The substitution of a halogen atom at the 5-position of
      isatin abolished the antiviral activity.

PMID- 17042333
TI  - Are we ready for a flu pandemic?

PMID- 17042334
TI  - "It's easy to be lured into nursing but I'm not sure I'd recommend it".

PMID- 17042335
TI  - 'Medicines management is not just a pharmacy issue'.

PMID- 17042336
TI  - Why we must stop needlestick injuries.

PMID- 17042338
TI  - The use of human tissue in bone grafting techniques.
AB  - The Medicines and Healthcare products Regulatory Agency has informed hospitals in
      England and Wales that bone graft material, which may include bone obtained
      illegally without consent, may have been implanted into a small number of UK
      patients. This article outlines the technique of bone grafting, examines the
      normal regulation and safety considerations and highlights the nursing
      implications surrounding this issue.

PMID- 17042337
TI  - Living life to the full. Interview by Clare Lomas.

PMID- 17042339
TI  - The urinary system. Part 1--introduction.

PMID- 17042340
TI  - Cancer genetics: the importance of obtaining a family history.
AB  - Cancer genetics is a rapidly evolving field that is becoming an integral part of
      a cancer patient's care. Until recently little genetics had been taught in the
      nursing curricula but a recent drive by the Department of Health is resulting in
      the integration of genetics into nurse training.

PMID- 17042341
TI  - Using a virtual care scenario to enhance student learning.
AB  - A series of care scenarios were developed entitled 'eWARD' that complement
      traditional teaching methods employed in the education of nursing students. This
      article discusses the development of one of these scenarios, which was based on a
      stroke rehabilitation theme, in relation to its theoretical underpinnings as well
      as its implementation and evaluation.

PMID- 17042343
TI  - Stars in their files.

PMID- 17042344
TI  - Food for thought.

PMID- 17042345
TI  - Specialist nursing under threat.

PMID- 17042346
TI  - Australia prioritises dementia.

PMID- 17042347
TI  - Healthy, wealthy and old?

PMID- 17042348
TI  - Shingles: relief at last.

PMID- 17042349
TI  - Future perfect or imperfect?

PMID- 17042350
TI  - Mental health and functional mental disorder in older adults.
AB  - The available literature on mental health and older people tends to focus on
      dementia rather than functional illness, despite the greater prevalence of the
      latter. This review analyses articles published on mental health in nursing
      journals and considers their content. The author suggests that those working with
      older adults need to hear more about the experiences of those who suffer with
      mental health problems.

PMID- 17042351
TI  - Introducing the Liverpool Care Pathway into nursing homes.
AB  - Around half a million older people aged 65 or over live in care homes across the
      UK and substantial numbers end their lives in these care settings. The Liverpool
      Care Pathway for the dying patient (LCP) was developed to transfer the hospice
      model of care into other care settings. This paper describes a pilot project to
      introduce the LCP into care homes local to the Queen Mary's Sidcup NHS Trust with
      a view to reducing the number of very ill elderly patients who are transferred to
      the acute trust from care homes and then die in A&E.

PMID- 17042352
TI  - Eva's view.

PMID- 17042353
TI  - Our health, our care, our say.

PMID- 17042354
TI  - Putting safety first.

PMID- 17042355
TI  - Carol Baxter.

PMID- 17042356
TI  - Knowledge management essential, not optional.

PMID- 17042357
TI  - Learning differently: e-learning in nurse education.

PMID- 17042358
TI  - Patient empowerment: myth or reality?

PMID- 17042359
TI  - Spirituality and health.

PMID- 17042360
TI  - Quality assurance of NHS funded healthcare education.

PMID- 17042361
TI  - Pay: mixed blessings for HCAs.

PMID- 17042362
TI  - Will you still need me?

PMID- 17042363
TI  - 'Finest of the fine arts'.
AB  - Florence Nightingale said nursing is 'the finest of the fine arts'. In the last
      of our Heart of Nursing series, we consider the similarities between nursing care
      and art.

PMID- 17042365
TI  - 'I turned my life around'.

PMID- 17042364
TI  - Mission to explain.
AB  - Lack of information adds to the fear of cancer for people from black and minority
      ethnic groups. Rose Thompson is making a difference.

PMID- 17042366
TI  - HIV carriers must be honest with prospective partners.

PMID- 17042367
TI  - Assessment of a patient with an acute exacerbation of asthma.
AB  - This article is a reflective account of the respiratory assessment of a patient
      experiencing an acute exacerbation of asthma in hospital. The patient's signs and
      symptoms are examined and an analysis of the respiratory assessment and the
      patient's treatment is provided.

PMID- 17042368
TI  - Cross-cultural information leaflets.
AB  - This article reflects on the development of leaflets in Urdu to support families
      in weaning children from milk to solids. Limitations in the translation process
      are highlighted and the importance of determining clients' needs is emphasised.

PMID- 17042369
TI  - Specialist palliative care for patients with non-cancer diagnosis.
AB  - All patients with palliative care needs should receive an equitable service, and
      there is evidence to suggest that patients with life-limiting illnesses other
      than cancer would benefit from specialist palliative care services. The author
      discusses how this might be achieved and the barriers that exist to prevent it
      happening.

PMID- 17042370
TI  - Assessment of learning in clinical practice.
AB  - This article explores assessment in clinical practice, including the measures
      that can be taken to ensure that it is conducted fairly and the appropriateness
      of the methods undertaken.

PMID- 17042371
TI  - Acute coronary care.

PMID- 17042372
TI  - A hard day's night.

PMID- 17042374
TI  - Free and easy.

PMID- 17042373
TI  - All together now.

PMID- 17042375
TI  - Identification of lipopolysaccharide-binding proteins in porcine milk.
AB  - Septicemia and endotoxemia initiated by bacterial lipopolysaccharide (LPS) are
      relatively common in suckling and weaned piglets. Maternal milk is a source of
      both nutrition and immune protection for piglets. Passive transfer of colostral
      antibodies is necessary for protection of neonatal piglets against diseases, but
      the concentration of immunoglobulins in milk rapidly declines during the 1st wk
      of lactation in all mammals. We hypothesized, therefore, that nonimmunoglobulin
      substances in milk contribute to the innate protection of neonates against
      septicemia during the suckling period. Using LPS-affinity chromatography for
      isolation of LPS-binding proteins and liquid chromatography-mass spectrometry for
      their identification, we identified in porcine milk the following proteins with
      LPS-binding capacity: lactoferrin, soluble CD14, serum amyloid A, alpha-S1
      casein, beta-casein, and kappa-casein. For lactoferrin, alpha-S1 casein, and
      kappa-casein, in vitro pepsin digestion did not inhibit LPS-binding activity,
      whereas combined digestion with pepsin and pancreatin abolished it. The biologic
      functions of these LPS-binding proteins and peptides were not determined.

PMID- 17042376
TI  - Influence of lidocaine and diazepam on peri-induction intraocular pressures in
      dogs anesthetized with propofol-atracurium.
AB  - The purpose of this study was to evaluate the effects on the intraocular pressure
      (IOP) of lidocaine or diazepam administered intravenously (IV) before induction
      of anesthesia with propofol-atracurium and orotracheal intubation in normal dogs,
      as well as the effects on the IOP of lidocaine applied topically to the larynx
      after induction with propofol-atracurium. We randomly assigned 32 random-source
      dogs, obtained from municipal pounds, to receive the following: lidocaine, 2
      mg/kg IV, with saline, 0.1 mL/kg topically applied to the larynx (LIDOsal);
      saline, 0.1 mL/kg IV, with lidocaine, 2 mg/kg topically applied to the larynx
      (SALlido); diazepam (Valium), 0.25 mg/kg IV, with saline, 0.1 mL/kg topically
      applied to the larynx (VALsal); or saline, 0.1 mL/kg IV, with saline, 0.1 mL/kg
      topically applied to the larynx (SALsal). We measured arterial pressure directly,
      by means of an indwelling catheter placed in a peripheral artery. Anesthesia was
      induced with propofol, 8 mg/kg IV, until loss of jaw tone, followed by
      atracurium, 0.3 mg/kg IV. We measured the IOP in triplicate in each eye before
      premedication, before induction, before intubation, and after intubation. After
      induction, the IOP was significantly increased except in the VALsal group, in
      which the IOP was significantly lower than in the negative-control group before
      intubation. After intubation, the IOP was significantly elevated in all the
      groups compared with the values before induction. Cardiovascular parameters were
      essentially similar in all the groups, except for a significant increase in blood
      pressure after intubation in the SALlido group. Thus, propofol-atracurium
      anesthesia causes an increase in IOP that is blunted by diazepam. However,
      diazepam does not blunt the increase in IOP observed with intubation.

PMID- 17042377
TI  - Postoperative effects of anesthesia and surgery on resting energy expenditure in
      horses as measured by indirect calorimetry.
AB  - In this study, we aimed to define the effects of anesthesia and surgery on the
      resting energy expenditure of horses in experimental conditions. Six horses were
      used in a longitudinal study with 2 study periods: before and after anesthesia
      and surgery. Every horse underwent a standard 90-min ventral midline exploratory
      laparotomy. Oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured,
      with the use of a closed-circuit spirometry system, on 5 consecutive days
      immediately before and after the surgery. In 3 consecutive 5-min periods each
      day, the expired air was collected in a Collins spirometer. Samples of the
      expired gas were drawn from the spirometer through a drying column into O2 and
      CO2 analyzers. Resting energy expenditure was calculated as [(VO2 STPD*3.94) +
      (VCO2 STPD*1.11)]*1.44. This study showed that anesthesia and ventral midline
      exploratory laparotomy in experimental conditions increase the postoperative
      caloric demand in horses by an average of 1.0 Mcal/d, which represents
      approximately a 10% increase (P = 0.03). Additional studies in critically ill
      horses after surgery are needed to determine their caloric needs and to optimize
      their nutritional management.

PMID- 17042378
TI  - Serodiagnostic comparison of enzyme-linked immunosorbent assay and surface
      plasmon resonance for the detection of antibody to porcine circovirus type 2.
AB  - This paper describes the cloning and expression of the capsid protein of Porcine
      circovirus type 2 (PCV2) in an Escherichia coli expression system that was used
      to produce a fusion protein for subsequent immunologic studies: enzyme-linked
      immunosorbent assay (ELISA) and surface plasmon resonance (SPR). Polymerase chain
      reaction was used to amplify the gene encoding the capsid protein from the DNA of
      PCV2. The protein was then cloned into a pRSET prokaryotic expression vector.
      Western blot analysis revealed that the recombinant protein gave strong signals
      on a polyvinylidene difluoride membrane when exposed to the serum from a pig
      infected with PCV2. The expressed protein was purified and used as an antigen for
      the ELISA and SPR study. A protein chip based on SPR was developed, and the
      diagnostic potential of SPR was compared with that of ELISA with the use of 70
      serum samples obtained from 6 pig farms. There was a strong positive correlation
      between the ELISA and SPR titers (r = 0.877, P < 0.01). Therefore, this
      recombinant capsid protein can be used as an antigen for serologic studies, and
      the SPR, a label-free method, appears to be a valuable and reproducible tool in
      the serodiagnosis of a PCV2 infection.

PMID- 17042379
TI  - The role of immunostimulation in the development of postweaning multisystemic
      wasting syndrome in pigs under field conditions.
AB  - We evaluated the effects of immunostimulation in the development of postweaning
      multisystemic wasting syndrome (PMWS) in 930 pigs 53 to 54 d old in a
      grower/finisher barn with a history of PMWS. The pigs were allocated to 5
      treatment groups: 4 groups received a single intramuscular injection of RespiSure
      ONE (a commercial Mycoplasma hyopneumoniae vaccine; n = 197), Emulsigen (an oil
      based adjuvant; n = 172), Alhydrogel (an aluminum-hydroxide-based adjuvant; n =
      172), or physiologic saline (n = 218); 1 group received no treatment (n = 171).
      Pigs affected by PMWS were found in all the groups. Antigen to Porcine circovirus
      type 2 (PCV-2) was detected by immunohistochemical testing within lesions of
      mesenteric lymph node, spleen, Peyer's patch, and lung of affected pigs. There
      was no significant difference in the incidence of PMWS among the groups. The
      findings indicate that immunostimulation did not influence the expression of PMWS
      in this study. Thus, routine vaccination against swine diseases may not
      significantly contribute to the occurrence of PMWS under field conditions.

PMID- 17042380
TI  - In vitro heterogeneity of osteogenic cell populations at various equine skeletal
      sites.
AB  - Bone cell cultures were evaluated to determine if osteogenic cell populations at
      different skeletal sites in the horse are heterogeneous. Osteogenic cells were
      isolated from cortical and cancellous bone in vitro by an explant culture method.
      Subcultured cells were induced to differentiate into bone-forming osteoblasts.
      The osteoblast phenotype was confirmed by immunohistochemical testing for
      osteocalcin and substantiated by positive staining of cells for alkaline
      phosphatase and the matrix materials collagen and glycosaminoglycans. Bone
      nodules were stained by the von Kossa method and counted. The numbers of nodules
      produced from osteogenic cells harvested from different skeletal sites were
      compared with the use of a mixed linear model. On average, cortical bone sites
      yielded significantly greater numbers of nodules than did cancellous bone sites.
      Between cortical bone sites, there was no significant difference in nodule
      numbers. Among cancellous sites, the radial cancellous bone yielded significantly
      more nodules than did the tibial cancellous bone. Among appendicular skeletal
      sites, tibial metaphyseal bone yielded significantly fewer nodules than did all
      other long bone sites. This study detected evidence of heterogeneity of equine
      osteogenic cell populations at various skeletal sites. Further characterization
      of the dissimilarities is warranted to determine the potential role heterogeneity
      plays in differential rates of fracture healing between skeletal sites.

PMID- 17042381
TI  - Cervical and coelomic radiologic features of the loggerhead sea turtle, Caretta
      caretta.
AB  - Many investigators have undertaken radiologic studies in chelonians. However,
      descriptive papers focusing on the radiographic anatomy are limited to only a few
      species. The purpose of this article is to provide the normal cervical and
      coelomic radiographic appearance of the loggerhead sea turtle (Caretta caretta),
      in the dorsoventral view, and to indicate useful landmarks to identify internal
      anatomic structures. Dorsoventral radiographs were taken of the neck and body of
      30 loggerhead sea turtles by means of analog and digital radiography. At various
      points, distortion or superimposition of images due to the natural curvature of
      the shell hindered the accuracy of interpretation. The pectoral and pelvic
      girdles were easily recognized. Important external landmarks included the
      vertebral and lateral scutes, and important internal landmarks included the
      bronchi, coracoid bones, the caudal border of the pulmonary fields, and the
      acetabulum.

PMID- 17042382
TI  - Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses
      and those with recurrent airway obstruction.
AB  - The aim of this work was to measure the myeloperoxidase (MPO) concentration in
      bronchoalveolar lavage (BAL) fluid collected from horses with recurrent airway
      obstruction (RAO), both in crisis and in remission, as well as from healthy
      horses. Seven horses with RAO were exposed to moldy hay until the maximum change
      in pleural pressure was greater than 1.5 kPa. At that point, BAL was performed,
      and the total cell counts and percentages in the fluid were immediately
      determined. To measure the MPO concentration in BAL-fluid supernatant, we used a
      specific enzyme-linked immunosorbent assay with polyclonal antibodies against
      equine MPO. The tests were repeated on the horses with RAO after they had spent 2
      mo on pasture. Six healthy horses serving as controls underwent the same tests.
      The absolute and relative neutrophil counts and the MPO concentration in the BAL
      fluid were significantly greater in the horses with an RAO crisis than in the
      control horses. After 2 mo on pasture, the horses that had been in RAO crisis
      were clinically normal, and their neutrophil counts and MPO levels in BAL fluid
      had significantly decreased; during remission their neutrophil counts were not
      significantly different from those in the healthy horses, but their MPO
      concentration remained significantly higher. This study showed that determining
      the MPO concentration in a horse's BAL fluid is technically possible and that
      during remission from RAO the concentration remains higher than normal. Thus, MPO
      may be a marker of neutrophil presence and activation in the lower airways.

PMID- 17042383
TI  - The impact of animal age, bacterial coinfection, and isolate pathogenicity on the
      shedding of porcine reproductive and respiratory syndrome virus in aerosols from
      experimentally infected pigs.
AB  - The objective of this study was to evaluate the role of different variables
      (animal age, bacterial coinfection, and isolate pathogenicity) on the shedding of
      Porcine reproductive and respiratory syndrome virus (PRRSV) in aerosols. Animals
      were grouped according to age (2 versus 6 mo) and inoculated with a PRRSV isolate
      of either low (MN-30100) or high (MN-184) pathogenicity. Selected animals in each
      group were also inoculated with Mycoplasma hyopneumoniae. The pigs were
      anesthetized and aerosol samples (1000 breaths/sample) collected on alternating
      days from 1 to 21 after PRRSV inoculation. The results indicated that animal age
      (P = 0.09), M. hyopneumoniae coinfection (P = 0.09), and PRRSV isolate
      pathogenicity (P = 0.15) did not significantly influence the concentration of
      PRRSV in aerosols. However, inoculation with the PRRSV MN-184 isolate
      significantly increased the probability of aerosol shedding (P = 0.00005; odds
      ratio = 3.22). Therefore, the shedding of PRRSV in aerosols may be isolate
      dependent.

PMID- 17042384
TI  - Prevalence of Brucella abortus antibodies in equines of a tropical region of
      Mexico.
AB  - A cross-sectional study was conducted to determinate the seroprevalence rate of
      equine brucellosis in the state of Tamaulipas, Mexico. Serum samples from 420
      equines were analyzed with the Rose Bengal test at cell concentrations of 3% (RBT
      3%) and 8% (RBT-8%), and positive results were confirmed with the Rivanol test
      (RT). Risk factors were determined with the prevalence ratio (PR) and the use of
      variables generated from a questionnaire administered to the animals' owners.
      Serum from 1 stallion had positive results with both the RBT-8% and the RT, for a
      seroprevalence rate of 0.238%. Drinking of water from a pond that was also used
      by cattle and dogs was the only associated risk factor for this animal (PR =
      0.25). However, the results were considered false-positive, because the results
      for other horses in the same environmental conditions were negative. Although
      brucellosis is considered endemic in ruminants in the study area, the results
      obtained suggest that equines are not a reservoir of brucellosis and do not play
      an important role in the epidemiologic patterns of this disease in northeastern
      Mexico.

PMID- 17042385
TI  - Plasma concentration of vitamin C in dogs with a portosystemic shunt.
AB  - Most mammals, including dogs, synthesize vitamin C in the liver. We measured the
      plasma concentration of vitamin C to assess the body vitamin C status in 15 dogs
      with a portosystemic shunt (PSS). The plasma biochemical parameters indicated
      liver abnormalities in all the dogs. In contrast, the plasma concentration of
      vitamin C ranged from 2.21 to 9.03 mg/L in the 15 dogs and was below the
      reference range (3.2 to 8.9 mg/L) in only 2 dogs. These findings suggest that
      vitamin C status is not impaired in dogs with PSS.

PMID- 17042386
TI  - Cardiorespiratory effects of desflurane in dogs given romifidine or medetomidine
      before induction of anesthesia with propofol.
AB  - The objective of this study was to evaluate the use of desflurane after induction
      of anesthesia with propofol in dogs sedated with romifidine or medetomidine. Each
      of 8 healthy dogs received intravenously, in random order, 3 preanesthetic
      protocols: romifidine, 40 microg/kg of body weight (BW) (R40); romifidine, 80
      microg/kg BW (R80); and medetomidine, 10 microg/kg BW (MED). Cardiovascular and
      respiratory variables were recorded during the procedure. Time to extubation,
      time to sternal recumbency, and time to standing were also recorded. Heart rate
      and respiratory rate decreased significantly during sedation from baseline
      values, but there were no differences between the means for the 3 preanesthetic
      protocols. Mean values for heart rate, mean arterial blood pressure, systolic
      arterial pressure, diastolic arterial pressure, respiratory rate, tidal volume,
      arterial oxygen saturation, end-tidal CO2 level, pH, and arterial blood gas
      values during anesthesia were similar for the 3 protocols. The mean end-tidal
      desflurane concentration was significantly lower with the R80 protocol than with
      the R40 protocol. The mean time to extubation was significantly shorter with the
      R40 protocol than with the R80 and MED protocols.

PMID- 17042387
TI  - Serum and urine concentrations of trypsinogen-activation peptide as markers for
      acute pancreatitis in cats.
AB  - The purpose of this study was to compare the clinical utility of the serum
      concentration of feline trypsin-like immunoreactivity (fTLI), the plasma and
      urine concentrations of trypsinogen-activation peptide (TAP), and the ratio of
      the urine TAP and creatinine concentrations (TAP:Cr) in the diagnosis of feline
      acute pancreatitis. We used 13 healthy cats and 10 cats with a diagnosis of acute
      pancreatitis. The mean serum fTLI and plasma TAP concentrations were
      significantly higher in the cats with acute pancreatitis than in the healthy cats
      (P < 0.05); the mean urine TAP concentrations and the median urine TAP:Cr ratios
      were not significantly different. Among the cats examined in this study, there
      was no benefit of plasma TAP over serum fTLI in the evaluation of suspected acute
      pancreatitis.

PMID- 17042388
TI  - The effects of equine skin preparation on transdermal drug penetration in vitro.
AB  - An increasing number of formulations are applied to equine skin, yet variable
      penetration can affect efficacy, or the incidence of adverse effects, or both. To
      investigate the effects of common methods of skin preparation on transdermal drug
      penetration in vitro, we clipped, harvested, and froze skin samples from 5
      Thoroughbred geldings. Thawed samples were prepared as follows: control (no
      preparation); cleaned with aqueous chlorhexidine (Aq-C, 0.1% w/v); cleaned with
      alcoholic chlorhexidine (Al-C, 0.5% w/v); shaved (Sh); or tape-stripped (Ta) with
      the use of adhesive tape. The samples were then placed in diffusion cells, and 2
      g of methylsalicylate (MeSa) gel (Dencorub) was applied to the stratum corneum
      side. The penetration of MeSa and its analyte, salicylate (Sa), through the skin
      samples was measured over 10 h. Compared with control skin, significantly more
      MeSa penetrated through skin prepared with Al-C or Sh (P < 0.01) or with Aq-C or
      Ta (P < 0.05), and significantly more Sa was recovered in the receptor phase from
      skin prepared with Aq-C, Al-C, or Sh (P < 0.05) or with Ta (P < 0.01). A
      significantly higher rate of penetration and shorter lag time were also noted for
      MeSa with all the prepared skin samples, compared with the control samples. The
      results show that clinical techniques routinely used to clean or prepare skin can
      significantly affect the rate and extent of penetration of a topically applied
      drug. This may result in greater systemic availability of active drug, which
      could lead to enhanced efficacy and, possibly, a higher incidence of adverse
      effects.

PMID- 17042389
TI  - Occurrence of esophageal and gastric cancer in Alaska Natives, 1969-2003.
AB  - BACKGROUND: Early reports of esophageal and gastric cancer in American
      Indians/Alaska Natives documented high rates. METHODS: Esophageal and gastric
      cancers in Alaska Natives were reviewed for 1969-2003 using the Alaska Native
      Tumor Registry database. Alaska Native incidence rates were age-adjusted and
      compared to rates of several US populations. RESULTS: The incidence of esophageal
      and gastric cancer has remained relatively stable during the 35-year period.
      Gastric cancer is higher than that seen in US Whites, Blacks and American Indians
      of New Mexico and similar US Asian/Pacific Islanders. Esophageal cancer incidence
      is higher than US Whites, Asian/Pacific Islanders and American Indians of New
      Mexico but similar to US Blacks. CONCLUSION: The rates of esophageal and gastric
      cancer in the Alaska Native population have remained high over 35 years. While
      the rate of gastric cancer has declined among US Whites, a similar decline has
      not been seen in Alaska Natives.

PMID- 17042390
TI  - WWAMI--Alaska's Medical School.
AB  - In 2005 Alaska's medical school is WWAMI, but the WWAMI program today is far
      different than it was in 1971 when it began with 5 Alaskans in a class of 9 at
      Fairbanks. WWAMI students may now complete nearly 3 years of the 4-year program
      in state. They can now complete postgraduate residency training at the Alaska
      Family Medicine Residency in Anchorage. Alaska also benefits from a host of other
      WWAMI initiatives, such as the MedCon medical consultation service. On the other
      hand, the Alaska WWAMI program still allows for only 10 medical school positions,
      as it has since its inception. In the face of a worsening physician shortage in
      the state, class expansion appears to be warranted. When comparing this option
      versus the costs of recruitment or the possibilities of increasing graduate
      medical education in the state, class size increase is well justified.

PMID- 17042391
TI  - The little boy from Bettles.

PMID- 17042393
TI  - Fifty? Prepare for the battle for your life.

PMID- 17042392
TI  - Generational approaches to current nursing issues. How younger and older nurses
      can coexist.

PMID- 17042394
TI  - Online lactation education tutorial.

PMID- 17042396
TI  - Changes in Alabama's Child Restraint law.

PMID- 17042395
TI  - Campaign for fragrance free health care in the U.S.

PMID- 17042397
TI  - Breastfeeding can reduce infant infections and health care costs.

PMID- 17042398
TI  - Accommodating the needs of the aging registered nurse workforce.
AB  - The average age of registered nurses is 45, according to the 2000 national Sample
      Survey of Registered Nurses as shown in results released in February 2002. With
      the nursing workforce aging and few young people entering the profession
      administrators will need to entertain ideas that will aid in retention of the
      older nurses. A descriptive survey design was used to determine the awareness of
      and any plans for the aging Registered Nurse (RN) workforce by Alabama nursing
      administrators in hospitals and nursing homes. The average of all responding
      facilities for employed RNs over the age of 55 is 11.78%, with hospitals average
      being 11.68% and nursing homes being 11.43%. Fifty-four percent of administrators
      were at least moderately aware of the aging workforce. There was a higher
      percentage noted in nursing homes (57%) than hospitals (40%). All administrators
      responded that they wished to retain older RNs. Unfortunately, 96.3% of Alabama
      hospitals and nursing homes have no policies currently in place to address the
      needs of the aging registered nurse workforce.

PMID- 17042399
TI  - Dementia: thief of hearts.

PMID- 17042400
TI  - Exploring the relation of independent and interdependent self-construals to why
      and how people pursue personal goals.
AB  - The authors examined whether independent or interdependent self-construals were
      associated with the way in which individuals pursued personal goals. Individuals
      with an independent self-construal orient toward personal-goal pursuit, whereas
      individuals with interdependent self-construal prioritize in-group goals above
      personal ones. The authors used a 1-week, prospective goal-setting paradigm. The
      present results revealed that interdependent self-construals were significantly
      associated with introjected reasons for pursuing goals, experiencing conflict
      among goals, and achieving less goal progress. Independent self-construals were
      significantly associated with intrinsic and identified reasons for goal pursuit
      and greater goal progress. There was some evidence that the relation of
      interdependent and independent self-construals to goal progress was mediated by
      goal conflict and goal intrinsic motivation, respectively. The present results
      also replicated previous research indicating the goal-setting benefits of
      intrinsic motivation, implementation intentions, and goal harmony.

PMID- 17042401
TI  - The influence of group diversity on intergroup bias following recategorization.
AB  - Although recategorization in laboratory studies of nominal groups has received
      considerable support, some researchers have criticized such efforts as impossible
      when demographic diversity is the source of group identification. Therefore, the
      purpose of the present study was to examine the influence of diversity on
      intergroup bias among groups where recategorization efforts had occurred. The
      author gathered data from 162 undergraduate students (as either 54 3-participant
      groups or 27 6-participant groups; 107 men and 55 women). Results of moderated
      regression analysis indicated that, although diversity did not influence
      participants' perceptions of the aggregate as a single group, diversity did
      influence intergroup bias. Specifically, bias was highest when more homogeneous
      groups merged with more diverse groups. The author discussed results in terms of
      theoretical contributions and implications for managing diversity.

PMID- 17042402
TI  - Correlates of minimal dating.
AB  - Researchers have associated minimal dating with numerous factors. The present
      author tested shyness, introversion, physical attractiveness, performance
      evaluation, anxiety, social skill, social self-esteem, and loneliness to
      determine the nature of their relationships with 2 measures of self-reported
      minimal dating in a sample of 175 college students. For women, shyness,
      introversion, physical attractiveness, self-rated anxiety, social self-esteem,
      and loneliness correlated with 1 or both measures of minimal dating. For men,
      physical attractiveness, observer-rated social skill, social self-esteem, and
      loneliness correlated with 1 or both measures of minimal dating. The patterns of
      relationships were not identical for the 2 indicators of minimal dating,
      indicating the possibility that minimal dating is not a single construct as
      researchers previously believed. The present author discussed implications and
      suggestions for future researchers.

PMID- 17042403
TI  - Relationship styles of self-focused autonomy, other-focused connection, and
      mutuality among Mexican American and European American college students.
AB  - The author examined relationship styles of self-focused autonomy (SFA), other
      focused connection (OFC), and mutuality among 415 European and Mexican American
      young adults in 2 U.S. colleges. Mutuality was the most commonly reported style
      for both ethnic groups, although Mexican American men were more likely than the
      others to indicate that they had the SFA style. Mexican American participants
      perceived their fathers' styles as SFA more often than did the others regarding
      either of their parents' styles. Mutuality was associated with the best mental
      health outcomes regardless of gender or ethnicity. The present results indicate
      that the cultural influences on autonomy and connection are complex and that
      collectivistic cultural contexts may sometimes promote autonomy concerns in men.

PMID- 17042404
TI  - Rethinking culture and self-construal: China as a middle land.
AB  - Amid criticisms of current paper-and-pencil type questionnaires measuring self
      construal across cultural groups, the authors used a graphic representation scale
      to examine whether Anglo Canadians (N = 220) were more independent than Mainland
      Chinese (N = 196) and Indians (N = 212) in construing their relationships with
      closest family member, family members, closest friend, friends, (other)
      relatives, colleagues, and neighbors. Data generated 5 intriguing findings: (a)
      Chinese were more interdependent than Canadians but less so than Indians,
      indicating that Chinese culture has become more individualistic. (b) Canadians
      were more independent than Chinese in 6 relationship dimensions but were as
      interdependent as Chinese in self-closest-friend connectedness, somewhat
      contradicting 1 assumption of theories of independent-interdependent self
      construal and individualism-collectivism (I-C). (c) Canadians were more
      independent than Indians in all relationship dimensions, supporting theories of
      independent-interdependent self-construal and I-C. (d) Chinese were as
      interdependent as Indians in self-closest-family-member, self-close-family
      members, and self-relatives connectedness but more independent than Indians in
      the other categories of self-other relationships. (e) Participants' age did not
      have strong correlations with variables measuring self-construal in any sample,
      indicating that a person's attachment style may not change greatly over a
      lifespan. The authors discussed theoretical and methodological implications.

PMID- 17042405
TI  - Queer in Southern MSW programs: lesbian and bisexual women discuss stigma
      management.
AB  - The author described the processes by which a sample of lesbian and bisexual
      women assessed and managed prejudice and discrimination while pursuing degrees of
      masters of social work. The author presented as being pivotal to the
      participants' assessments of social work settings the social cues that
      participants identified as indicative of potential attitudes and beliefs
      regarding lesbian and bisexual women. In addition, the author discussed
      strategies that the women used to manage others' expression of prejudicial
      attitudes. Through these interactional processes, the participants demonstrated
      that they were active in shaping and reducing their experience of oppression.

PMID- 17042406
TI  - Procrastination and demographic characteristics in Spanish adults: further
      evidence.

PMID- 17042407
TI  - Benevolent sexism and cosmetic use: a replication with three college samples and
      one adult sample.

PMID- 17042408
TI  - Wisconsin's health disparities challenge physicians.

PMID- 17042409
TI  - Further need for EC awareness and access.

PMID- 17042410
TI  - Clinical use of evidence-based medicine--clinical questions: Acetylcysteine, a
      new treatment for an old foe?
AB  - This is a small, good quality, randomized controlled trial that shows a modest
      slowing in the deterioration of VC and DLco with the addition of high dose N
      acetylcysteine to standard therapy in IPF. Overall the study should be
      interpreted with caution given its high drop out rate, which may have biased the
      results towards a more dramatic slowing of the disease progression. There were no
      differences in dyspnea score or functional status. There was no increase in the
      adverse events in the N-acetylcysteine group and the medication is inexpensive.
      Given only modest effects of N-acetylcysteine on VC and DLco, no change in
      functional scores, and the flaws of the study we would hesitate to use N
      acetylcysteine as standard therapy in all patients with IPF.

PMID- 17042411
TI  - Wisconsin Medical Society embarks on campaign to define high-quality care.

PMID- 17042412
TI  - Proposed constitutional amendment means restrictions of health care access.
AB  - It is difficult to read all of the current studies about sexual orientation and
      not hypothesize that some combination of genetic and developmental factors must
      be involved. It seems likely that homosexuality is a trait like left handedness.
      Treating our gay, lesbian, bisexual, or transgender patients any differently than
      we treat our left handed patients makes no sense. And voting for the proposed
      constitutional amendment that would deny them access to health care doesn't make
      sense either.

PMID- 17042413
TI  - An evidence-based context to address health care for gay and lesbian patients.
AB  - There is extensive, credible evidence in the medical literature, and overwhelming
      consensus among professional medical organizations, that disparities in health
      care provided to gay and lesbian patients and their families must be addressed
      and changed. As physicians, we continue to assess the latest medical evidence in
      order to provide the highest quality health care to all our patients. We will
      tell the truth when attempts to discriminate, whether legislative or societal,
      harm our patients or hamper our ability to care for them. Examples from Michigan,
      Ohio, and Nebraska, where constitutional amendments banning same sex civil unions
      or marriage have passed, are noteworthy, with increasing legal challenges to
      domestic partnerships. These discriminatory laws and amendments have jeopardized
      health care decision-making, hospital visitation rights, health insurance, and
      legal protections for gay as well as heterosexual couples. In Wisconsin, we can
      and must do better than that as we strive to improve the health of all of our
      citizens.

PMID- 17042414
TI  - Medication costs in Wisconsin Medicaid: Waste not, want not?

PMID- 17042415
TI  - CA-MRSA triangulation: virulent strains, susceptible hosts, and contaminated
      environments.

PMID- 17042416
TI  - Monitoring racial/ethnic mortality disparities in Wisconsin: 1991-2000.
AB  - BACKGROUND: Wisconsin has a goal to eliminate health disparities by 2010, but
      there is no consistent standard used to evaluate progress. Methodological debates
      persist regarding using individual group change or relative comparisons to
      monitor disparities. OBJECTIVES: To examine mortality disparities among
      racial/ethnic populations in Wisconsin using statistically significant changes in
      individual population mortality rates and rate ratios as measures of disparity.
      These measures are proposed to monitor and evaluate progress in eliminating
      racial/ethnic health disparities. METHODS: The Wisconsin Interactive Statistics
      on Health database was queried to obtain Wisconsin all-cause mortality data by
      race and age for the 1991-1995 and 1996-2000 periods. Age-specific and age
      adjusted rates were compared across 5 major racial/ethnic populations in
      Wisconsin. RESULTS: Age-adjusted mortality generally declined for all
      racial/ethnic populations in Wisconsin from 19911995 to 1996-2000. However,
      disparities increased significantly for African American infants, African
      Americans 45-64 years old, and Hispanics/Latinos 25-44 years old. Using non
      Hispanic whites as a referent resulted in a paradoxical increase in disparities
      for Hispanics/Latinos despite a significant reduction in mortality in this group.
      CONCLUSION: A statistically significant percent change in mortality rates and
      rate ratios is a useful standard to monitor health disparities and foster
      communication and targeted action around Wisconsin's goal to eliminate
      racial/ethnic health disparities.

PMID- 17042417
TI  - Disparities in oral and pharyngeal cancer incidence and mortality among Wisconsin
      residents, 1999-2002.
AB  - OBJECTIVE: Compare incidence, mortality, and trends of oral cancer (including the
      pharynx) in Wisconsin and the United States by race and gender from 1999-2002.
      METHODS: Age-adjusted incidence rates were compared using data from the Centers
      for Disease Control and Prevention (CDC WONDER). Mortality rates were compared
      using data from the Wisconsin Interactive Statistics on Health (WISH) and CDC US
      Cancer Statistics. RESULTS: Incidence rates for oral cancer were higher among
      males than females in both Wisconsin and the United States. Trends in the
      incidence rate show the gender disparity has not changed. Furthermore, the
      incidence rate for African American males is higher in Wisconsin than in the
      United States. Mortality rates for males were approximately 2 times higher than
      females in Wisconsin and the United States. Additionally, African American males
      are more likely than white males to die from this form of cancer, and the
      likelihood is higher in Wisconsin than in the United States (2.4 versus 1.8,
      respectively). CONCLUSION: Racial disparities in oral cancer for African American
      males are greater in Wisconsin than in the United States. This may result from
      variation in access to oral health care, tobacco and alcohol use, as well as
      limited resources in detection and prevention methods. Wisconsin should focus its
      oral cancer prevention activities on this high-risk group.

PMID- 17042418
TI  - Analysis of anti-epileptic drugs in fee-for-service Wisconsin Medicaid.
AB  - INTRODUCTION: Off-label use of prescription drugs presents issues of patient
      safety and can significantly increase the overall prescription drug expenditure
      in providing health care services. As a class, the anti-epileptic drugs are
      provided for off-label use on a frequent basis. Because of the safety issues and
      increased cost with such prescribing practices, the Wisconsin Medicaid Drug
      Utilization Review Board (DUR board) reviewed the use of anti-epileptic agents in
      the fee-for-service Wisconsin Medicaid population. METHODS: Prescribers with the
      highest amount paid for drugs in this class, and for which there was no
      appropriate diagnosis (intervention group), were provided with a list of the
      patients for whom they prescribed the drug for an off-label clinical condition. A
      total of 488 prescribers were contacted and informed of the costs and hazards of
      off-label prescribing. RESULTS: Using a comparison group of patients who were
      prescribed anti-epileptic agents but who did not reach the amount paid threshold
      (non-intervention group), the study demonstrated a decrease of 6652 prescriptions
      in the intervention group and an increase of 4194 in the non-intervention group.
      In addition, expenditures for the intervention group dropped by dollar 752,232
      and the non-intervention group rose by dollar 835,351. It is estimated that the
      overall financial impact of this intervention was a savings of dollar 2,552,077
      over the 5-month period of review.

PMID- 17042419
TI  - Community acquired methicillin resistant Staphylococcus aureus: A Wisconsin
      perspective.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus have swept across
      the United States, causing severe morbidity and mortality (see Table 1). This
      manuscript provides some illustrative cases seen in Wisconsin.

PMID- 17042420
TI  - Injuries from ultimate frisbee.
AB  - OBJECTIVE: This paper will explore ultimate frisbee injuries. METHOD: This study
      uses an anonymous, retrospective, self-reported survey of 135 adult athletes at a
      Midwestern ultimate frisbee tournament. Subjects were queried regarding injuries
      to specific body parts, those causing missed activity, recurring injuries,
      medical care sought, basic demographic data, duration of participation,
      handedness, and eye color. Categorical data were analyzed by chi-square tests.
      Qualitative responses were categorized by themes. RESULTS: Respondents had a mean
      age of 28 years and 59% were male. Mean playing time was 8.2 hours per week and
      7.5 total years. Ultimate frisbee injuries included muscle strains (76% of
      subjects), ankle (65%), knee (53%), shoulder (37%), head (30%), and rib (21%)
      injuries. Blisters/calluses and black toenails were frequently mentioned.
      Recurrent injuries were reported in 49%. Shoulder injuries were more common in
      men than women (47% versus 24%, P<0.02). Of respondents, 88% have missed ultimate
      frisbee activity due to injury, and 71% have sought medical care for ultimate
      frisbee injuries. CONCLUSIONS: The majority of surveyed ultimate frisbee players
      experience injuries and seek medical care. Health care professionals should be
      aware of the injuries associated with ultimate frisbee and further studies should
      focus on prevention and education strategies.

PMID- 17042421
TI  - Is the ankle-brachial index a useful screening test for subclinical
      atherosclerosis in asymptomatic, middle-aged adults?
AB  - BACKGROUND: Measurement of the ankle-brachial index (ABI) is recommended as a
      screening test for cardiovascular risk prediction in individuals > or = 50 years
      old; however, there is little data regarding the utility of the ABI as a
      screening test in individuals for whom physicians actually order non-invasive
      testing for cardiovascular risk prediction. METHODS: This study included 493
      consecutive asymptomatic patients without known atherosclerotic vascular disease
      who were referred by their physician for measurement of the ABI and ultrasound
      measurement of carotid intima-media thickness (CIMT). ABI values were classified
      as "reduced" (<0.9), "normal" (0.9-1.3), and "increased" (>1.3). RESULTS: The
      mean age of the patients was 55.3 (standard deviation 7.5) years. Only 1 patient
      had a reduced ABI (0.2%). ABI values tended to be higher in those with increased
      CIMT (P=0.051); however, CIMT was not significantly different between those with
      normal and increased ABI values (P=0.802). There were no significant differences
      in the prevalence of traditional cardiovascular risk factors or carotid plaque
      presence among the ABI groups. CONCLUSIONS: Despite recommendations, the ABI is
      not sensitive as a screening tool for detecting subclinical atherosclerosis in
      asymptomatic middle-aged individuals.

PMID- 17042422
TI  - Northern Wisconsin married couple infected with blastomycosis.
AB  - Blastomycosis is an uncommon, chronic, granulomatous disease caused by the
      dimorphic fungus Blastomycosis dermatitidis. The great majority of infections
      start with primary pulmonary involvement through inhalation of spores.
      Hematogenous dissemination to other sites occurs in 25% to 30% of cases. The most
      common secondary site is the skin, followed in order by bone, genitourinary
      system, and central venous system. We report 2 cases of blastomycosis originating
      in a husband and wife who were both symptomatic and diagnosed with blastomycosis
      within 4 months of each other. One presented with pulmonary symptoms, the other
      with cutaneous symptoms. These 2 cases of husband and wife are of interest not
      only because of their rarity but also because of the potential mode of
      transmission.

PMID- 17042423
TI  - Advancing the Wisconsin idea.

PMID- 17042424
TI  - Want to retire early? How to avoid the 10% penalty.

PMID- 17042425
TI  - MetaStar's health care and culture project: does your clinic meet federal
      standards?

PMID- 17042426
TI  - [The question of Gretchen in Faust..A quality the qualified nurse has to
      anticipate].

PMID- 17042427
TI  - [We gain nothing from blocking].

PMID- 17042428
TI  - [Integration of quality health nursing into a clear concept].

PMID- 17042429
TI  - [The reason for recognizing the patient's needs].

PMID- 17042430
TI  - [Different "management" in old age].

PMID- 17042431
TI  - [Regional networking].

PMID- 17042432
TI  - [Indications for a new tariff system].

PMID- 17042433
TI  - [When help becomes a crime].

PMID- 17042434
TI  - [Fundamentals in our calling].

PMID- 17042435
TI  - [Great demands with deadly outcomes].

PMID- 17042436
TI  - ["I have had the possibility of experimenting with collaboration."].

PMID- 17042437
TI  - [No tiny nurse, nor any superior nursing help].

PMID- 17042438
TI  - [A "non-suicide contract" under the guise of prevention].

PMID- 17042439
TI  - [Health education and professional promotion].

PMID- 17042440
TI  - [Many words and few deeds].

PMID- 17042441
TI  - ["I am fascinated by the wealth of the continuity of nursing"].

PMID- 17042442
TI  - A sedation dental practice.

PMID- 17042443
TI  - Dental anesthesiology--an access to care issue.

PMID- 17042444
TI  - Current sedation practice in Israel.

PMID- 17042445
TI  - Dentist anesthesiologists.

PMID- 17042446
TI  - Sedation and safety: 36 years of perspective.

PMID- 17042447
TI  - Use of midazolam to modify children's behavior in the dental setting.

PMID- 17042448
TI  - Effective and safe pediatric oral conscious sedation: philosophy and practical
      considerations.
AB  - Because dental treatment can represent a threatening event for some children,
      need exists to include sedation within our management arsenal. By definition, pre
      cooperative children and those lacking in cooperative ability have immature
      cognitive skills, a highly restricted range of coping abilities, brief or
      negligible attention spans, and virtually no experience coping with stress. As
      result, they can be especially prone to maladaptive responses to anxiety
      provoking situations. For many of these, traditional non-pharmacologic behavior
      management strategies may often prove inadequate or inappropriate to overcome
      resistive or uncooperative behaviors. The importance of intervention with non
      aversive techniques that provide a safe, child-oriented environment and timely
      opportunity in which to encounter and cope with fear-producing situations cannot
      be dismissed. The use of sedation techniques can frequently serve to obtund
      interfering and potentially harmful behaviors to safely permit quality care,
      minimize or eliminate the need for aversive measures, and help bridge the
      transition for a child lacking cooperative ability to the time when cooperation
      potential develops.

PMID- 17042449
TI  - Easing the grip of patients' fear.

PMID- 17042450
TI  - You had to be there to believe it!

PMID- 17042451
TI  - Hurricanes' aftermath lingers on.

PMID- 17042452
TI  - New standards emphasize emotional well-being.

PMID- 17042453
TI  - Top 50 nursing facility chains & top 40 assisted living chains.

PMID- 17042454
TI  - A case for consistent assignment.

PMID- 17042455
TI  - Inviting lifestyles, caring people.

PMID- 17042456
TI  - Depression and the MDS.

PMID- 17042457
TI  - QIOS assist in the transfer to technology.

PMID- 17042458
TI  - Shedding a new light on chronic ailments.

PMID- 17042459
TI  - Keeping influenza in check.

PMID- 17042460
TI  - Constructing a building contract.

PMID- 17042461
TI  - VA shapes new telehealth model.

PMID- 17042462
TI  - Holistic and biomedical concepts of health: a study of health notions among
      Swedish occupational therapists and a suggestion for developing an instrument for
      comparative studies.
AB  - The objectives of this study were to inquire into notions of health among a group
      of 439 Swedish occupational therapists and to test a model derived from a
      qualitative study by Bjorklund & Svensson with a representative sample of
      occupational therapists in Sweden. The data were collected through a
      questionnaire and were analyzed using descriptive statistics, cluster analysis,
      and confirmatory factor analysis. The means and ranking of the health notions
      showed that Swedish occupational therapists most frequently hold holistic notions
      of health, and to a lesser extent biostatistical ones. Most Swedish occupational
      therapists indicate that being clearly conscious of one's health notions is
      important both to themselves and to their profession. The test of the model
      provides a step towards developing an instrument for measuring notions of health
      that clearly distinguishes between holistic and biomedical ones and that could
      possibly be used for comparative studies.

PMID- 17042463
TI  - Occupational therapists' reflection on practice within psychiatric care: a Delphi
      study.
AB  - AIM: The aim of this study was to describe the reflections on practice in a group
      of Swedish occupational therapists in psychiatric care in order to illuminate the
      present practice and ideas about the future using a Delphi survey of three
      rounds. MATERIAL AND METHOD: The sample consisted of 14 occupational therapists
      in psychiatric care. The answers from the first and second rounds illustrate the
      wide variation in their practice. The third round points out consensus and
      disagreements in the domains: professional role, theories in practice, domain of
      concern, occupational therapy assessment, goal setting/treatment,
      outcome/evaluation and thoughts about the future. A consensus was reached in all
      domains, but not regarding competence to treat functional reduction and symptoms,
      or on the importance of theories for documentation, the choice of a theoretical
      foundation, and the importance of an evidence-based treatment model, although the
      theories were seen as supporting practice. Disagreements were found as to the
      effectiveness of repeated assessments as a means of evaluation. The future for
      OTs within psychiatric care was looked upon as positive. DISCUSSION: The results
      developed from providing a relatively unclear and shallow perspective on OT
      practice to indicating a depth that shows what occupational therapy within
      psychiatry can be. During the process it became more and more clear how OTs think
      and act.

PMID- 17042464
TI  - Leaving homelessness and addiction: narratives of an occupational transition.
AB  - The aim of this exploratory study was to gain an understanding of occupational
      aspects of homelessness and of the transition from homelessness. Data were
      collected through narrative interviews of two formerly homeless women recovering
      from drug addiction. Data were analyzed using a constant comparative method
      followed by a narrative analysis. The findings first identified homelessness as a
      life of high intensity lived within a limited time perspective. Further, for
      these women homelessness was related to drug addiction, which was experienced at
      first as a solution to life situations that seemed impossible to handle. Second,
      the analysis showed how social relationships can strengthen or change the lived
      plots of the participants. Third, the transition out of homelessness was
      accomplished through the development and enactment of new lived plots. Finally
      the analysis showed that life as formerly homeless women was experienced as less
      intense and as a life that can only partly be controlled. This new life includes
      a broader time perspective. In the discussion, the relationship between time use
      and the meaning-making process and possible practical implications of this study
      are presented.

PMID- 17042465
TI  - Experiences within the process of sick leave.
AB  - The aim of this study was to explore what individuals who have been on sick leave
      experienced as important in the process of returning to work, moving to long-term
      sick leave, or receiving a disability pension. Grounded Theory was used for
      interpreting interviews with 15 people who had been on sick leave four years
      previously. In the results four ideal types were crystallized which are presented
      in the form of vignettes. The ideal types were discussed focusing on occupational
      life using the Model of Human Occupation and the theories of Sense of Coherence
      and Status Passage. The study provided a deeper understanding of people's
      experiences during the process of their sick leave. Valuable predictors for re
      entry into work or disability retirement were: individual mental resources; clear
      or unclear diagnosis; how long had been spent in the sick-leave process; and
      personal belief in an ability to work in the future. The interventions and
      support given by professionals and the social environment, the balance and sense
      of coherence in life, and participation in the sick leave process were also
      important. The idealtypes found could be helpful to professionals working in this
      field in deepening their understanding of the clients.

PMID- 17042466
TI  - Spinal cord injured persons' conceptions of hospital care, rehabilitation, and a
      new life situation.
AB  - BACKGROUND: The basic aim of spinal cord injury (SCI) rehabilitation is to help
      patients return to a life worth living. It is therefore important that the staff
      at spinal units and rehabilitation centres understand how the patients experience
      their rehabilitation and their adjustment process to the new situation. AIM: To
      describe SCI persons' experiences of their rehabilitation process. METHOD:
      Nineteen SCI persons were interviewed. Data from the tape-recorded interviews
      were analysed according to a modified descriptive version of the phenomenographic
      analysis process. RESULTS: Six categories that describe the informants'
      conceptions of their rehabilitation process emerged: access to information,
      participation in planning rehabilitation, emotional support, feelings of
      vulnerability, adjustment to a new life situation, and emotional consequences of
      the injury. CONCLUSION: Straightforward information, participation in the
      planning of the rehabilitation programme and emotional support were important
      factors influencing the rehabilitation process after the SCI. Professionals
      working with SCI rehabilitation should make use of patients' experiences in order
      to develop better rehabilitation programmes that focus on the individual needs of
      the patient. People are individuals and failure to take this into account can
      impact negatively on quality of life and the effectiveness of the rehabilitation.

PMID- 17042467
TI  - Life satisfaction in early rheumatoid arthritis: a prospective study.
AB  - The aim of this study was to describe life satisfaction prospectively in patients
      with early rheumatoid arthritis (RA) and to investigate its correlation with
      disease activity. The early RA group was compared with RA patients with
      longstanding disease and with a reference group. Gender differences were also
      compared. Patients with early RA, treated by a multidisciplinary team, reported
      their life satisfaction by completing a questionnaire. Disease activity score,
      patient global assessment, and pain were scored at onset of disease and after two
      years. The patients with early RA were less satisfied with life as a whole at
      disease onset compared with the reference group, as was a cohort of patients with
      longstanding disease. Patients with early RA also reported low levels of
      satisfaction with self-care activities, work, and sexual life. The women reported
      themselves more satisfied than men. After two years, a slight increase in the
      reported levels of satisfaction could be seen for life as a whole and for five of
      the eight domains. No correlation was found between disease activity variables
      and satisfaction with life as a whole. There were, however, positive correlations
      between disease activity and satisfaction both with partnership and with family
      life after two years, i.e. the higher disease activity the higher satisfaction
      with partnership relation and family life. In contrast, patients with greater
      disease activity were less satisfied with self-care activities. The results of
      this study indicate that greater effort is needed to assist patients with early
      RA to cope with problems concerning self-care activities, sexual life, and work.

PMID- 17042468
TI  - Cooperative binding and multiple recognition by bridged bis(beta-cyclodextrin)s
      with functional linkers.
AB  - Possessing two beta-cyclodextrin cavities in close vicinity and a functional
      linker with good structural variety in a single molecule, bridged bis(beta
      cyclodextrin)s can significantly enhance the original binding ability and
      molecular selectivity of native beta-cyclodextrin and thus be successfully
      utilized in drug carriers, solubilizers, catalysis, photochemical materials, etc.
      This Account describes recent developments in the intramolecular cooperative
      binding and multiple recognition of bridged bis(beta-cyclodextrin)s with
      functional linkers in solution, as well as their molecular assembly behaviors
      through the intermolecular cooperative binding. It also gives a description of
      unique properties and wide applications of bis(beta-cyclodextrin)s and their
      assemblies.

PMID- 17042469
TI  - Alpha-c-galactosylceramides: synthesis and immunology.
AB  - The immunostimulant activity of alpha-galactosylceramides provided the impetus
      for the research described here. The activity was first discovered via screening
      of extracts of a marine sponge. The active materials purified from the extracts
      were alpha-O-galactosylceramides. The work described herein focuses on syntheses
      of alpha-C-galactosylceramides. Crucial methodologies for the syntheses were (i)
      Ramberg-Backlund reaction, (ii) modified Julia olefination, (iii) olefin cross
      metathesis, and (iv) Sharpless asymmetric epoxidation in four independent routes.
      The immunostimulant activity of the synthetic alpha-C-galactosylceramide far
      surpasses that of the O-galactosyl material. A discussion of the reasons for the
      difference in activity is presented.

PMID- 17042470
TI  - Polymer-induced flip-flop in biomembranes.
AB  - This Account describes the ability of amphiphilic polymers (e.g., EO/PO/EO block
      copolymers) and polycations [e.g., quaternized poly(4-vinylpyridine)] to
      accelerate translocation from the inside leaflet to the outside leaflet ("flip
      flop") within vesicle bilayer membranes. Driving forces and mechanisms of flip
      flop catalyzed by the nonionic and cationic polymers are different. The nonionics
      are bound to the biological membrane via incorporation of their hydrophobic
      blocks into the inner part of the lipid bilayer occupied by the hydrocarbon
      chains. The resulting scrambling of lipid molecules is favored by the overall
      hydrophobicity of the copolymer and the volume of its hydrophobic block. External
      binding of the cationic polymers, on the other hand, is driven by electrostatic
      interactions between the positively charged polymer units and the negatively
      charged lipid headgroups within the outside leaflet. Electrostatic binding favors
      both the flip-flop of anionic lipid from the inner to outer leaflet and the
      formation of anionic domains in the outer leaflet. When it is considered that
      less than 1% of the liposome surface is occupied by certain bound polymers, their
      effect upon membrane dynamics, as will be described herein, is considerable. A
      distinct correlation has been found between the "flippase" activity of the
      polymers and their ability to mediate drug permeation through biomembranes.

PMID- 17042471
TI  - P-Phos: a family of versatile and effective atropisomeric dipyridylphosphine
      ligands in asymmetric catalysis.
AB  - This Account outlines our efforts in the design and synthesis of a family of
      highly effective atropisomeric dipyridylphosphine ligands (P-Phos and its
      variants) and in the development of their widespread applications in transition
      metal-catalyzed asymmetric reactions including hydrogenation, hydrosilylation,
      and C-C bond formation. Desirable attributes, such as air stability, broad
      substrate scope, fast rates of reaction, excellent enantioselectivities, low
      catalyst loading, and mild conditions, make the catalyst systems highly
      attractive and thus may provide excellent opportunities for practical
      applications.

PMID- 17042472
TI  - Metallo-beta-lactamases: novel weaponry for antibiotic resistance in bacteria.
AB  - Metallo-beta-lactamases are broad-spectrum zinc enzymes, able to inactivate most
      clinically useful beta-lactam antibiotics. Their structural and functional
      diversity has thus far limited the understanding of their catalytic mechanism,
      therefore thwarting the rational design of a common inhibitor. On the basis of
      the recent availability of structures of enzyme-product complexes and novel
      mechanistic studies, here, we attempt to find minimal common elements in
      different members of this family. In contrast with other metalloenzymes, most of
      the substrate binding and catalytic power resides in the adequate positioning of
      one or two Zn(II) ions in the active site, empowered by an unusual flexibility.

PMID- 17042473
TI  - Modeling enzymatic reactions involving transition metals.
AB  - High-accuracy quantum chemistry has now been applied for almost 10 years to
      biological problems involving transition metal active sites. The leading
      theoretical method is hybrid density functional theory (DFT), usually with the
      B3LYP functional. The chemical models vary in size, commonly from 30 to 100 atoms
      treated fully quantum mechanically. Two schools exist, one using the smallest
      possible adequate models and the other using as large models as possible and
      sometimes including the entire enzyme by combining quantum mechanics with
      molecular mechanics. In our group, we have found that the latter approach, which
      is much more time-consuming and error prone, is seldom needed. In this Account,
      methods and models will be described and examples of recent applications given.
      The examples are chosen to illustrate trends and to show cases where theory has
      predicted new mechanisms not suggested previously.

PMID- 17042474
TI  - Catalytically active gold: from nanoparticles to ultrathin films.
AB  - Ordered gold (Au) mono- and bilayer structures have been synthesized on a highly
      reduced titania surface. The Au bilayer exhibits a significantly higher catalytic
      activity for carbon monoxide oxidation than does the Au monolayer structure. This
      is the first report of Au completely wetting an oxide surface and demonstrates
      that ultrathin Au films on an oxide surface have exceptionally high catalytic
      activity, comparable to the activity observed for Au nanoparticles. This
      discovery is a key to understanding the nature of the active site of supported Au
      catalysts.

PMID- 17042475
TI  - Predicting the stereochemistry of diphenylphosphino benzoic acid (DPPBA)-based
      palladium-catalyzed asymmetric allylic alkylation reactions: a working model.
AB  - Palladium-catalyzed asymmetric allylic alkylation has proven to be a powerful
      method for the preparation of a wide variety of chiral compounds and the rapid
      assembly of complex molecular architecture from simple starting materials. While
      many types of catalyst systems have been successfully employed with certain
      systems, diphenylphosphino benzoic acid (DPPBA) based ligands have found use over
      a broad range of substrate classes. This Account highlights the mechanistic
      aspects considered when designing reactions with DPPBA-based ligands and presents
      a working model for the a priori prediction of their stereochemical outcome.

PMID- 17042476
TI  - Super radical stabilizers.
AB  - A comprehensive series of substituted 1,1-dimethyl-2-methylenecyclopropanes have
      been thermally rearranged. These rearrangements proceed via singlet biradical
      intermediates that can be stabilized by substituents. Rates are greatly enhanced
      by certain groups that are termed super radical stabilizers. Substituents
      included 4-pyridyl N-oxide, 2-(1,6-methano[10]annulenyl), and a number of anion
      substituted phenyl groups. Simple valence bond theory, as well as more
      sophisticated computational studies, gives insights into modes of radical
      stabilization.

PMID- 17042477
TI  - How do low-energy (0.1-2 eV) electrons cause DNA-strand breaks?
AB  - We overview our recent theoretical predictions and the innovative experimental
      findings that inspired us concerning the mechanisms by which very low-energy (0.1
      2 eV) free electrons attach to DNA and cause strong (ca. 4 eV) covalent bonds to
      break causing so-called single-strand breaks. Our primary conclusions are that
      (i) attachment of electrons in the above energy range to base pi* orbitals is
      more likely than attachment elsewhere and (ii) attachment to base pi* orbitals
      most likely results in cleavage of sugar-phosphate C-O sigma bonds. Later
      experimental findings that confirmed our predictions about the nature of the
      electron attachment event and about which bonds break when strand breaks form are
      also discussed. The proposed mechanism of strand break formation by low-energy
      electrons involves an interesting through-bond electron-transfer process.

PMID- 17042478
TI  - Antibodies with infinite affinity: origins and applications.
AB  - Antibodies with infinite affinity were developed with the aim of improving
      targeted delivery of metal complexes to sites of disease. This is part of a
      series of chemical technology developments for biomedical imaging and therapy.
      Using a combination of genetics and chemical synthesis, it addresses challenges
      in developing proteins that specifically bind synthetic molecules and do not
      release them. The result is a set of reagents that promise to capture any of a
      large variety of metallic elements under physiological conditions and hold them
      for long periods of time.

PMID- 17042479
TI  - Structural and electron paramagnetic resonance (EPR) studies of mononuclear
      molybdenum enzymes from sulfate-reducing bacteria.
AB  - Molybdenum and tungsten are found in biological systems in a mononuclear form in
      the active site of a diverse group of enzymes that generally catalyze oxygen-atom
      transfer reactions. The metal atom (Mo or W) is coordinated to one or two
      pyranopterin molecules and to a variable number of ligands such as oxygen (oxo,
      hydroxo, water, serine, aspartic acid), sulfur (cysteines), and selenium
      (selenocysteines) atoms. In addition, these proteins contain redox cofactors such
      as iron-sulfur clusters and heme groups. All of these metal cofactors are along
      an electron-transfer pathway that mediates the electron exchange between
      substrate and an external electron acceptor (for oxidative reactions) or donor
      (for reductive reactions). We describe in this Account a combination of
      structural and electronic paramagnetic resonance studies that were used to reveal
      distinct aspects of these enzymes.

PMID- 17042480
TI  - Enantiomeric free radicals and enzymatic control of stereochemistry in a radical
      mechanism: the case of lysine 2,3-aminomutases.
AB  - The product of yjeK in Escherichia coli is a homologue of lysine 2,3-aminomutase
      (LAM) from Clostridium subterminale SB4, and both enzymes catalyze the
      isomerization of (S)- but not (R)-alpha-lysine by radical mechanisms. The
      turnover number for LAM from E. coli is 5.0 min(-1), 0.1% of the value for
      clostridial LAM. The reaction of E. coli LAM with (S)-alpha-[3,3,4,4,5,5,6,6
      (2)H8]lysine proceeds with a kinetic isotope effect (kH/kD) of 1.4, suggesting
      that hydrogen transfer is not rate-limiting. The product of the E. coli enzyme is
      (R)-beta-lysine, the enantiomer of the clostridial product. Beta-lysine-related
      radicals are observed in the reactions of both enzymes by electron paramagnetic
      resonance (EPR). The radical in the reaction of clostridial LAM has the (S)
      configuration, whereas that in the reaction of E. coli LAM has the (R)
      configuration. Moreover, the conformations of the beta-lysine-related radicals at
      the active sites of E. coli and clostridial LAM are different. The nuclear
      hyperfine splitting between the C3 hydrogen and the unpaired electron at C2 shows
      the dihedral angle to be 6 degrees, unlike the value of 77 degrees reported for
      the analogous radical bound to the clostridial enzyme. Reaction of (S)-4
      thialysine produces a substrate-related radical in the steady state of E. coli
      LAM, as in the action of the clostridial enzyme. While (S)-beta-lysine is not a
      substrate for E. coli LAM, it undergoes hydrogen abstraction to form an (S)-beta
      lysine-related radical with the same stereochemistry of hydrogen transfer from C2
      of (S)-beta-lysine to the 5'-deoxyadenosyl radical as in the action of the
      clostridial enzyme. The resulting beta-lysyl radical has a conformation different
      from that at the active site of clostridial LAM. All evidence indicates that the
      opposite stereochemistry displayed by E. coli LAM is determined by the
      conformation of the lysine side chain in the active site. Stereochemical models
      for the actions of LAM from C. subterminale and E. coli are presented.

PMID- 17042481
TI  - Identification of structural and catalytic classes of highly conserved amino acid
      residues in lysine 2,3-aminomutase.
AB  - Lysine 2,3-aminomutase (LAM) from Clostridium subterminale SB4 catalyzes the
      interconversion of (S)-lysine and (S)-beta-lysine by a radical mechanism
      involving coenzymatic actions of S-adenosylmethionine (SAM), a [4Fe-4S] cluster,
      and pyridoxal 5'-phosphate (PLP). The enzyme contains a number of conserved
      acidic residues and a cysteine- and arginine-rich motif, which binds iron and
      sulfide in the [4Fe-4S] cluster. The results of activity and iron, sulfide, and
      PLP analysis of variants resulting from site-specific mutations of the conserved
      acidic residues and the arginine residues in the iron-sulfide binding motif
      indicate two classes of conserved residues of each type. Mutation of the
      conserved residues Arg134, Asp293, and Asp330 abolishes all enzymatic activity.
      On the basis of the X-ray crystal structure, these residues bind the epsilon
      aminium and alpha-carboxylate groups of (S)-lysine. However, among these
      residues, only Asp293 appears to be important for stabilizing the [4Fe-4S]
      cluster. Members of a second group of conserved residues appear to stabilize the
      structure of LAM. Mutations of arginine 130, 135, and 136 and acidic residues
      Glu86, Asp165, Glu236, and Asp172 dramatically decrease iron and sulfide contents
      in the purified variants. Mutation of Asp96 significantly decreases iron and
      sulfide content. Arg130 or Asp172 variants display no detectable activity,
      whereas variants mutated at the other positions display low to very low
      activities. Structural roles are assigned to this latter class of conserved amino
      acids. In particular, a network of hydrogen bonded interactions of Arg130, Glu86,
      Arg135, and the main chain carbonyl groups of Cys132 and Leu55 appears to
      stabilize the [4Fe-4S] cluster.

PMID- 17042482
TI  - Structure of testis ACE glycosylation mutants and evidence for conserved domain
      movement.
AB  - Human angiotensin-converting enzyme is an important drug target for which little
      structural information has been available until recent years. The slow progress
      in obtaining a crystal structure was due to the problem of surface glycosylation,
      a difficulty that has thus far been overcome by the use of a glucosidase-1
      inhibitor in the tissue culture medium. However, the prohibitive cost of these
      inhibitors and incomplete glucosidase inhibition makes alternative routes to
      minimizing the N-glycan heterogeneity desirable. Here, glycosylation in the
      testis isoform (tACE) has been reduced by Asn-Gln point mutations at N
      glycosylation sites, and the crystal structures of mutants having two and four
      intact sites have been solved to 2.0 A and 2.8 A, respectively. Both mutants show
      close structural identity with the wild-type. A hinge mechanism is proposed for
      substrate entry into the active cleft, based on homology to human ACE2 at the
      levels of sequence and flexibility. This is supported by normal-mode analysis
      that reveals intrinsic flexibility about the active site of tACE. Subdomain II,
      containing bound chloride and zinc ions, is found to have greater stability than
      subdomain I in the structures of three ACE homologues. Crystallizable
      glycosylation mutants open up new possibilities for cocrystallization studies to
      aid the design of novel ACE inhibitors.

PMID- 17042483
TI  - Architecture of a gamma retroviral genomic RNA dimer.
AB  - Retroviral genomes contain two sense-strand RNAs that are noncovalently linked at
      their 5' ends, forming a dimer. Establishing a structure for this dimer is an
      obligatory first step toward understanding the fundamental role of the dimeric
      RNA in retroviral biology. We developed a secondary structure model for the
      minimal dimerization active sequence (MiDAS) for the Moloney murine sarcoma virus
      in the final dimer state using selective 2'-hydroxyl acylation analyzed by primer
      extension (SHAPE). In this model, two self-complementary, or palindromic,
      sequences (PAL1 and PAL2) form extended intermolecular duplexes of 10 and 16 base
      pairs, respectively. The monomeric starting state was shown previously to contain
      a flexible domain in which nucleotides do not form stable interactions with other
      parts of the RNA. In the final dimer state, portions of this initial flexible
      domain form stable base pairs, while previously base-paired elements lie in a new
      flexible domain. Thus, partially overlapping and structurally well-defined
      flexible domains are prominent features of both monomer and dimer states. We then
      used hydroxyl radical cleavage experiments to characterize the global
      architecture of the dimer state. Extensive regions, including portions of both
      PAL1 and PAL2, are occluded from solvent-based cleavage indicating that the MiDAS
      domain does not function simply as a collection of autonomous secondary structure
      elements. Instead, the retroviral dimerization domain adopts a compact
      architecture characterized by close packing of its constituent helices.

PMID- 17042484
TI  - A hyperthermophilic protein acquires function at the cost of stability.
AB  - Active-site residues are not often optimized for conformational stability
      (activity-stability trade-offs) in proteins from organisms that grow at moderate
      temperature. It is unknown if the activity-stability trade-offs can be applied to
      proteins from hyperthermophiles. Because enzymatic activity usually increases at
      higher temperature and hyperthermophilic proteins need high conformational
      stability, they might not sacrifice the stability for their activity. This study
      attempts to clarify the contribution of active-site residues to the
      conformational stability of a hyperthermophilic protein. We therefore examined
      the thermodynamic stability and enzymatic activity of wild-type and active-site
      mutant proteins (D7N, E8A, E8Q, D105A, and D135A) of ribonuclease HII from
      Thermococcus kodakaraensis (Tk-RNase HII). Guanidine hydrochloride (GdnHCl)
      induced denaturation was measured with circular dichroism at 220 nm, and heat
      induced denaturation was studied with differential scanning calorimetry. Both
      GdnHCl- and heat-induced denaturation were highly reversible in these proteins.
      All the mutations of these active-site residues, except that of Glu8 to Gln,
      reduced the enzymatic activity dramatically but increased the protein stability
      by 7.0 to 11.1 kJ mol(-1) at 50 degrees C. The mutation of Glu8 to Gln did not
      seriously affect the enzymatic activity and increased the stability only by 2.5
      kJ mol(-1) at 50 degrees C. These results indicate that hyperthermophilic
      proteins also exhibit the activity-stability trade-offs. Therefore, the
      architectural mechanism for hyperthermophilic proteins is equivalent to that for
      proteins at normal temperature.

PMID- 17042485
TI  - Role of the S128, H186, and N187 triad in substrate binding and decarboxylation
      in the sheep liver 6-phosphogluconate dehydrogenase reaction.
AB  - Crystal structures of 6-phosphogluconate dehydrogenase (6PGDH) from sheep liver
      indicate that S128 and N187 are within hydrogen-bonding distance of 6PG in the
      E:6PG binary complex and NADPH in the E:NADPH binary complex. In addition, H186
      is also within hydrogen-bonding distance of NADPH in the E:NADPH binary complex,
      while in the E:6PG binary complex it is within hydrogen-bonding distance of S128
      and close to N187. The structures suggest that this triad of residues may play a
      dual role during the catalytic reaction. Site-directed mutagenesis has been
      performed to mutate each of the three residues to alanine. All mutant enzymes
      exhibit a decrease in V/E(t) (the turnover number), ranging from 7- to 67-fold.
      An increase in the Km for 6PG (K(6PG)) was observed for S128A and H187A mutant
      enzymes, while for the H186A mutation, K(6PG) is decreased by a factor of 2.
      K(NADP) remains the same as the wild type enzyme for the S128A and H186A mutant
      enzyme, while it increases by 6-fold in the N187A mutant enzyme. An increased
      K(iNADPH) was measured for all of the mutant enzymes. The primary kinetic 13C
      isotope effect is increased, while the primary deuterium kinetic isotope effect
      is decreased, indicating that the decarboxylation step has become more rate
      limiting under conditions where substrate is limiting. A quantitative analysis of
      the data suggests that the S128, H186, and N187 triad is multifunctional in the
      6PGDH reaction and contributes as follows. The triad (1) participates in the
      precatalytic conformational change; (2) provides ground state binding affinity
      for 6PG and NADPH; and (3) affects the relative rates of reduction or
      decarboxylation of the 3-keto-6PG intermediate by anchoring the cofactor after
      hydride transfer, which is accompanied by the rotation of the nicotinamide ring
      around the N-glycosidic bond and displacement of C1 of 6PG, facilitating
      decarboxylation.

PMID- 17042486
TI  - Crystal structures of the Synechocystis photoreceptor Slr1694 reveal distinct
      structural states related to signaling.
AB  - Crystal structures of the Synechocystis BLUF phototaxis photoreceptor Slr1694
      have been determined in two crystal forms, a monoclinic form at 1.8 A resolution
      and an orthorhombic form at 2.1 A resolution. In both forms, the photoreceptor is
      comprised of two pentamer rings stacked face to face. Twenty total subunits in
      the two asymmetric units of these crystal forms display three distinct tertiary
      structures that differ in the length of the fifth beta-strand and in the
      orientation of Trp91, a conserved Trp residue near the FMN chromophore.
      Fluorescence spectroscopic analysis on Slr1694 in solution is consistent with
      motion of Trp91 from a hydrophobic environment in the dark state to a more
      hydrophilic environment in the light-excited state. Mutational analysis indicates
      that movement of Trp91 is dependent on the occupancy of the hydrophobic Trp
      binding pocket with a nearby Met. These different tertiary structures may be
      associated with absorption changes in the blue region of the spectrum.

PMID- 17042487
TI  - The inhibitor protein (IF1) promotes dimerization of the mitochondrial F1F0-ATP
      synthase.
AB  - The effect of increased expression or reconstitution of the mitochondrial
      inhibitor protein (IF1) on the dimer/monomer ratio (D/M) of the rat liver and
      bovine heart F1F0-ATP synthase was studied. The 2-fold increased expression of
      IF1 in AS-30D hepatoma mitochondria correlated with a 1.4-fold increase in the
      D/M ratio of the ATP synthase extracted with digitonin as determined by blue
      native electrophoresis and averaged densitometry analyses. Removal of IF1 from
      rat liver or bovine heart submitochondrial particles increased the F1F0-ATPase
      activity and decreased the D/M ratio of the ATP synthase. Reconstitution of
      recombinant IF1 into submitochondrial particles devoid of IF1 inhibited the F1F0
      ATPase activity by 90% and restored partially the D/M ratio of the whole F1F0
      complex as revealed by blue native electrophoresis and subsequent SDS-PAGE or
      glycerol density gradient centrifugation. Thus, the inhibitor protein promotes or
      stabilizes the dimeric form of the intact F1F0-ATP synthase. A possible location
      of the IF1 protein in the dimeric structure of the rat liver F1F0 complex is
      proposed. According to crystallographic and electron microscopy analyses, dimeric
      IF1 could bridge the F1-F1 part of the dimeric F1F0-ATP synthase in the inner
      mitochondrial membrane.

PMID- 17042488
TI  - Structure of the membrane reconstituted transmembrane-juxtamembrane peptide
      EGFR(622-660) and its interaction with Ca2+/calmodulin.
AB  - The transmembrane (TM) and juxtamembrane (JM) regions of the epidermal growth
      factor receptor (EGFR) couple ligand binding in the extracellular domain to
      activation of the kinase domain. Solid-state NMR and polarized FTIR measurements
      of peptides corresponding to the TM plus JM regions of EGFR (residues 622-660)
      reconstituted in model phospholipid membranes are presented to address the role
      of the short cytoplasmic JM sequence (residues 645-660) in regulating EGFR
      activity. We show that the TM domain is helical with a transition to non-helical
      structure at the TM-JM boundary. Fluorescence measurements indicate that the JM
      region of EGFR(622-660) binds to the membrane surface and that binding can be
      reversed by the addition of the complex of Ca2+ and calmodulin. Together these
      data support models suggesting the cytoplasmic JM region of EGFR plays an active
      role in regulating receptor activity.

PMID- 17042489
TI  - Role of threonine 101 on the stability of the heme active site of cytochrome
      P450cam: multiwavelength circular dichroism studies.
AB  - The role of the threonine 101 residue that resides close to the heme propionic
      acid side chain of cytochrome P450cam on the conformational properties of the
      active site of the enzyme has been investigated by circular dichroism (CD)
      spectroscopy. Site-specific mutation of the threonine by valine has been carried
      out that does not affect the size of the residue but significantly alters the
      hydropathy index. The T101V mutant of cytochrome P450cam showed distinct
      differences in the CD spectra near the heme region, indicating a subtle effect of
      the mutation on the properties of the heme active site. Thermal stabilities of
      the mutant and wild-type enzyme have been studied by temperature dependence of
      the ellipticity (intensity of the CD band) in the far-UV region for the secondary
      structure and at different wavelengths in the visible region that arise from the
      heme moiety for the tertiary structure around the prosthetic group. The thermal
      unfolding data from variations of the CD intensity at different wavelengths were
      analyzed using a generalized multistep unfolding model, and two distinct
      equilibrium intermediate conformational states of the enzyme were identified. The
      mutation of the T101 residue by valine was found to decrease the thermal
      stability of both the intermediates in the presence of the substrate. On the
      other hand, this mutation had no apparent effect on the thermal stability of the
      enzyme in the absence of the substrate. These results suggested that the
      threonine residue stabilizes the protein cavity around the heme center in the
      case of the substrate-bound species, possibly by hydrogen bonding with one of the
      propionate side chains of the heme moiety. Such hydrogen bonding of the heme
      propionate with threonine is absent in the substrate-free form of the enzyme.

PMID- 17042490
TI  - Binding of polyaminocarboxylate chelators to the active-site copper inhibits the
      GSNO-reductase activity but not the superoxide dismutase activity of Cu,Zn
      superoxide dismutase.
AB  - In addition to its superoxide dismutase (SOD) activity, Cu,Zn-superoxide
      dismutase (CuZnSOD) catalyzes the reductive decomposition of S-nitroso-L
      glutathione (GSNO) in the presence of thiols such as L-glutathione (GSH). The
      GSNO-reductase activity but not the superoxide dismutase (SOD) activity of
      CuZnSOD is inhibited by the commonly used polyaminocarboxylate metal ion
      chelators, EDTA and DTPA. The basis for this selective inhibition is
      systematically investigated here. Incubation with EDTA or DTPA caused a time
      dependent decrease in the 680 nm d-d absorption of Cu(II)ZnSOD but no loss in SOD
      activity or in the level of metal loading of the enzyme as determined by ICP-MS.
      The chelators also protected the SOD activity against inhibition by the arginine
      specific reagent, phenylglyoxal. Measurements of both the time course of SNO
      absorption decay at 333 nm and oxymyoglobin scavenging of the NO that is released
      confirmed that the chelators inhibit CuZnSOD catalysis of GSNO reductive
      decomposition by GSH. The decreased GSNO-reductase activity is correlated with
      decreased rates of Cu(II)ZnSOD reduction by GSH in the presence of the chelators
      as monitored spectrophotometrically at 680 nm. The aggregate data suggest binding
      of the chelators to CuZnSOD, which was detected by isothermal titration
      calorimetry (ITC). Dissociation constants of 0.08 +/- 0.02 and 8.3 +/- 0.2 microM
      were calculated from the ITC thermograms for the binding of a single EDTA and
      DTPA, respectively, to the CuZnSOD homodimer. No association was detected under
      the same conditions with the metal-free enzyme (EESOD). Thus, EDTA and DTPA must
      bind to the solvent-exposed active-site copper of one subunit without removing
      the metal. This induces a conformational change at the second active site that
      inhibits the GSNO-reductase but not the SOD activity of the enzyme.

PMID- 17042491
TI  - Time-resolved FTIR difference spectroscopy for the study of photosystem I
      particles with plastoquinone-9 occupying the A1 binding site.
AB  - In photosystem I from plants and cyanobacteria a phylloquinone molecule, called
      A1, functions as the secondary electron acceptor. In cyanobacteria, genes that
      encode for proteins involved in phylloquinone biosynthesis can be deleted. Here,
      we have studied three different gene deletion mutants called menB, menD, and menE
      mutants. In these mutants, plastoquinone-9 occupies the A1 binding site. Using
      time-resolved, step-scan FTIR difference spectroscopy we have produced A1(-)/A1
      FTIR difference spectra for menB, menD, and menE photosystem I particles at 77 K.
      These difference spectra show that the P700 triplet state ((3)P700) is formed in
      a large fraction of the particles. Infrared spectral signatures that are not due
      to (3)P700 are also observed in the spectra and are suggested to be associated
      with plastoquinone-9 anion formation in a portion of the particles. By
      subtracting the known (3)P700 spectral signatures, we produce an A1(-)/A1 FTIR
      difference spectrum for PS I particles with plastoquinone-9 occupying the binding
      site. This spectrum shows that a band that we have previously assigned to a C:-O
      mode of the phylloquinone anion in WT A1(-)/A1 FTIR DS down-shifts approximately
      8 cm(-1) when plastoquinone-9 occupies the A1 binding site. Using density
      functional theory type calculations to produce anion minus neutral infrared
      difference spectra for both phylloquinone and plastoquinone-9, it is shown that
      such a downshift is reasonable. A1(-)/A1 FTIR difference spectra, obtained using
      menB mutant photosystem I particles that were incubated in the presence of
      phylloquinone, are found to be very similar to those obtained using normal WT
      photosystem I particles. This result indicates that we were able to reincorporate
      phylloquinone back into the A1 binding site and that the reincorporated
      phylloquinone and its immediate protein environment, in both the neutral and
      anion state, are very similar to that found in wild type photosystem I particles.
      For the reconstituted menB mutant photosystem I particles, no spectral signatures
      associated with (3)P700 are observed, indicating that phylloquinone occupies the
      A1 site in all of the reconstituted menB particles.

PMID- 17042492
TI  - Structural basis of the ferrous iron specificity of the yeast ferroxidase, Fet3p.
AB  - Fet3p is a multicopper oxidase (MCO) that functions together with the iron
      permease, Ftr1p, to support high-affinity Fe uptake in yeast. Fet3p is a
      ferroxidase that, like ceruloplasmin and hephaestin, couples the oxidation of 4
      equiv of Fe(II) to the reduction of O2 to 2 H2O. The ferrous iron specificity of
      this subclass of MCO proteins has not been delineated by rigorous structure
      function analysis. Here the crystal structure of Fet3p has been used as a
      template to identify the amino acid residues that confer this substrate
      specificity and then to quantify the contributions they make to this specific
      reactivity by thermodynamic and kinetic analyses. In terms of the Marcus theory
      of outer-sphere electron transfer, we show here that D283, E185, and D409 in
      Fet3p provide a Fe(II) binding site that actually favors ferric iron; this site
      thus reduces the reduction potential of the bound Fe(II) in comparison to that of
      aqueous ferrous iron, providing a thermodynamically more robust driving force for
      electron transfer. In addition, E185 and D409 constitute parts of the electron
      transfer pathway from the bound Fe(II) to the protein's type 1 Cu(II). This
      electronic matrix coupling relies on H-bonds from the carboxylate OD2 atom of
      each residue to the NE2 NH group of the two histidine ligands at the type 1 Cu
      site. These two acidic residues and this H-bond network appear to distinguish a
      fungal ferroxidase from a fungal laccase since the specificity that Fet3p has for
      Fe(II) is completely lost in a Fet3pE185A/D409A mutant. Indeed, this double
      mutant functions kinetically better as a laccase, albeit a relatively inefficient
      one.

PMID- 17042493
TI  - Redox thermodynamics of the Fe(III)/Fe(II) couple of human myeloperoxidase in its
      high-spin and low-spin forms.
AB  - Myeloperoxidase (MPO) (donor, hydrogen peroxide oxidoreductase, EC 1.11.1.7) is
      the most abundant neutrophil enzyme and catalyzes predominantly the two-electron
      oxidation of ubiquitous chloride (Cl-), to generate the potent bleaching oxidant
      hypochlorous acid (HOCl), thus contributing to bacterial killing and inflammatory
      reactions of neutrophils. Here, the thermodynamics of the one-electron reduction
      of the ferric heme in its ferric high-spin and cyanide-bound low-spin forms were
      determined through spectroelectrochemical experiments. The E(o)' values for free
      and cyanide-bound MPO (5 and -37 mV, respectively, at 25 degrees C and pH 7.0)
      are significantly higher than those of other heme peroxidases. Variable
      temperature experiments revealed that the enthalpic stabilization of ferric high
      spin MPO is much weaker than in other heme peroxidases and is exactly compensated
      by the entropic change upon reduction. In contrast to those of other heme
      peroxidases, the stabilization of the ferric cyanide-bound MPO is also very weak
      and fully entropic. This peculiar behavior is discussed with respect to the MPO
      typical covalent heme to protein linkages as well as to the published structures
      of ferric MPO and its cyanide complex and the recently published structure of
      lactoperoxidase as well as the physiological role of MPO in bacterial killing.

PMID- 17042494
TI  - Facile detection of acyl and peptidyl intermediates on thiotemplate carrier
      domains via phosphopantetheinyl elimination reactions during tandem mass
      spectrometry.
AB  - With the emergence of drug resistance and the genomic revolution, there has been
      a renewed interest in the genes that are responsible for the generation of
      bioactive natural products. Secondary metabolites of one major class are
      biosynthesized at one or more sites by ultralarge enzymes that carry covalent
      intermediates on phosphopantetheine arms. Because such intermediates are
      difficult to characterize in vitro, we have developed a new approach for
      streamlined detection of substrates, intermediates, and products attached to a
      phosphopantetheinyl arm of the carrier site. During vibrational activation of gas
      phase carrier domains, facile elimination occurs in benchtop and Fourier
      transform mass spectrometers alike. Phosphopantetheinyl ejections quickly reduce
      >100 kDa megaenzymes to <1000 Da ions for structural assignment of intermediates
      at <0.007 Da mass accuracy without proteolytic digestion. This "top down"
      approach quickly illuminated diverse acyl intermediates on the carrier domains of
      the nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs) found
      in the biosynthetic pathways of prodigiosin, pyoluteorin, mycosubtilin,
      nikkomycin, enterobactin, gramicidin, and several proteins from the orphan pksX
      gene cluster from Bacillus subtilis. By focusing on just those regions undergoing
      covalent chemistry, the method delivered clean proof for the reversible
      dehydration of hydroxymethylglutaryl-S-PksL via incorporation of 2H or 18O from
      the buffer. The facile nature of this revised assay will allow diverse
      laboratories to spearhead their NRPS-PKS projects with benchtop mass
      spectrometers.

PMID- 17042495
TI  - Delayed release of inorganic phosphate from elongation factor Tu following GTP
      hydrolysis on the ribosome.
AB  - The dissociation of inorganic phosphate (P(i)) following GTP hydrolysis is a key
      step determining the functional state of many GTPases. Here, the timing of P(i)
      release from elongation factor Tu (EF-Tu) and its implications for the function
      of EF-Tu on the ribosome were studied by rapid kinetic techniques. It was found
      that P(i) release from EF-Tu is >20-fold slower than GTP cleavage and limits the
      rate of the conformational switch of EF-Tu from the GTP- to the GDP-bound form.
      The point mutation Gly94Ala in the switch 2 region of EF-Tu abolished the delay
      in P(i) release, suggesting that P(i) release is controlled by the mobility of
      the switch 2 region with Gly94 acting as a pivot. The rate of P(i) release or the
      conformational switch of EF-Tu does not affect the selection of aminoacyl-tRNA on
      the ribosome. Rather, the slow P(i) release may be a consequence of the tight
      interaction of the switch regions of EF-Tu with the gamma-phosphate and the
      ribosome in the GTPase activated state of the factor.

PMID- 17042496
TI  - Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of
      the human pyruvate dehydrogenase multienzyme complex through alternating sites
      cofactor activation.
AB  - Recent kinetic and structural studies on various thiamin-dependent enzymes,
      including the bacterial E1 component of the pyruvate dehydrogenase complex
      (PDHc), suggested an active center communication between the cofactors in these
      multimeric enzymes. This regulatory mode has been inferred from the dissymmetry
      of active sites in proteolytic patterns and X-ray structures and from a complex
      macroscopic kinetic behavior not being consistent with independently working
      active sites. Here, direct microscopic kinetic evidence for this hypothesis is
      presented for the alpha2beta2-type E1 component of the human pyruvate
      dehydrogenase complex. Only one of the two thiamin molecules bound to the two
      active sites is in a chemically activated state exhibiting an apparent C2
      ionization rate constant of approximately 50 s(-1) at pH 7.6 and 30 degrees C,
      whereas the thiamin in the "inactive site" ionizes with a rate that is at least 3
      orders of magnitude smaller. The chemical nonequivalence is also exhibited in the
      ability to bind the substrate analogue methyl acetylphosphonate and in the
      catalytic turnover of the substrate pyruvate in the E1-only reaction. In the
      activated active site, pyruvate is rapidly bound and decarboxylated with apparent
      forward rate constants of covalent pyruvate binding of 2 s(-1) and
      decarboxylation of the formed 2-lactyl-thiamin intermediate of 5 s(-1). In the
      dormant site, these steps are as slow as 0.03 s(-1). Under the conditions that
      were used, only the heterotetramer can be detected by analytical
      ultracentrifugation, thus ruling out the possibility that multiple oligomeric
      species with different reactivities cause the observed kinetic effects. The
      results are consistent with the recently suggested model of an active site
      synchronization in PDHc-E1 via a proton wire that keeps the two active sites in
      an alternating activation state [Frank, R. A., et al. (2004) Science 306, 872].
      Kinetic studies on the related thiamin enzymes transketolase, pyruvate oxidase,
      and bacterial pyruvate decarboxylase are not consistent with a chemical and/or
      functional nonequivalence of the active sites as observed in the E1 component of
      hsPDHc. We hypothesize that the alternating sites reaction in PDHc-E1 aids in the
      synchronized acyl transfer to the E2 component in the highly organized
      multienzyme complex.

PMID- 17042497
TI  - Chimeric thermostable DNA polymerases with reverse transcriptase and attenuated
      3'-5' exonuclease activity.
AB  - The synthesis of accurate, full-length cDNA from low-abundance RNA and the
      subsequent PCR amplification under conditions which provide amplicon that
      contains minimal mutations remain a difficult molecular biological process. Many
      of the challenges associated with performing sensitive, long RT/PCR have been
      alleviated by using a mixture of DNA polymerases. These mixtures have typically
      contained a DNA polymerase devoid of 3'-5' exonuclease, or "proofreading",
      activity blended with a small amount of an Archaea DNA polymerase possessing 3'
      5' exonuclease activity, since reverse transcriptases lack 3'-5' exonuclease
      activity and generally have low fidelity. To create a DNA polymerase with
      efficient reverse transcriptase and 3'-5' exonuclease activity, a family of
      mutant DNA polymerases with a range of attenuated 3'-5' exonuclease activities
      was constructed from a chimeric DNA polymerase derived from Thermus species Z05
      and Thermotoga maritima DNA polymerases. These "designer" DNA polymerases were
      fashioned using structure-based tools to identify amino acid residues involved in
      the substrate-binding site of the exonuclease domain of a thermostable DNA
      polymerase. Mutation of some of these residues resulted in proteins in which DNA
      polymerase activity was unaffected, while proofreading activity ranged from 60%
      of the wild-type level to undetectable levels. Kinetic characterization of the
      exonuclease activity indicated that the mutations affected catalysis much more
      than binding. On the basis of their specificity constants (kcat/KM), the mutant
      enzymes have a 5-15-fold stronger preference for a double-stranded mismatched
      substrate over a single-stranded substrate than the wild-type DNA polymerase, a
      desirable attribute for RT/PCR. The utility of these enzymes was evaluated in a
      RT/PCR assay to generate a 1.7 kb amplicon from HIV-1 RNA.

PMID- 17042498
TI  - Structure and function of prokaryotic glutamate transporters from Escherichia
      coli and Pyrococcus horikoshii.
AB  - The glutamate transporters GltP(Ec) from Escherichia coli and GltP(Ph) from
      Pyrococcus horikoshii were overexpressed in E. coli and purified to homogeneity
      with a yield of 1-2 mg/L of culture. Single-particle analysis and electron
      microscopy indicate that GltP(Ph) is a trimer in detergent solution. Electron
      microscopy of negatively stained GltP(Ph) two-dimensional crystals shows that the
      transporter is a trimer also in the membrane. Gel filtration of GltP(Ec)
      indicates a reversible equilibrium of two oligomeric states in detergent solution
      that we identified as a trimer and hexamer by blue-native gel electrophoresis and
      cross-linking. The purified transporters were fully active upon reconstitution
      into liposomes, as demonstrated by the uptake of radioactively labeled L
      aspartate or L-glutamate. L-aspartate/L-glutamate transport of GltP(Ec) involves
      the cotransport of protons and depends only on pH, whereas GltP(Ph) catalyzes L
      glutamate transport with a cotransport of H+ or Na+. L-glutamate induces a fast
      transient current in GltP(Ph) proteoliposomes coupled to a solid supported
      membrane (SSM). We show that the electric signal depends on the concentration of
      Na+ or H+ outside the proteoliposomes and that GltP(Ph) does not require K+
      inside the proteoliposomes. In addition, the electrical currents are inhibited by
      TBOA and HIP-B. The half-saturation concentration for activation of GltP(Ph)
      glutamate transport (K0.5(glut)) is 194 microM.

PMID- 17042499
TI  - Nature and significance of the interactions between amyloid fibrils and
      biological polyelectrolytes.
AB  - Charged polyelectrolytes such as glycosaminoglycans and nucleic acids have
      frequently been found associated with the proteinaceous deposits in the tissues
      of patients with amyloid diseases. We have investigated the nature and generality
      of this phenomenon by studying the ability of different polyanions, including
      DNA, ATP, heparin, and heparan sulfate, to promote the aggregation of
      amyloidogenic proteins and to bind to the resulting aggregates. Preformed amyloid
      fibrils of human muscle acylphosphatase and human lysozyme, proteins with a net
      positive charge at physiological pH values, were found to bind tightly to the
      negatively charged DNA or ATP. The effects of the polyelectrolytes on the
      kinetics of aggregation were studied for acylphosphatase, and the presence of
      ATP, DNA, or heparin was found to increase its aggregation rate dramatically,
      with a degree dependent on the net charge and size of the polyanion. Magnesium or
      calcium ions were found to attenuate, and ultimately to suppress, these
      interactions, suggesting that they are electrostatic in nature. Moreover, heparin
      was found to stabilize the aggregated state of acylphosphatase through
      compensation of electrostatic repulsion. Noteworthy, differences in affinity
      between native and aggregated acylphosphatase with heparin suggest that amyloid
      fibrils can themselves behave as polyelectrolytes, interacting very strongly with
      other polyelectrolytes bearing the opposite charge. Within an in vivo context,
      the strengthening of the electrostatic interactions with other biological
      polyelectrolytes, as a consequence of protein misfolding and aggregation, could
      therefore result in depletion of essential molecular components and contribute to
      the known cytotoxicity of amyloid fibrils and their precursors.

PMID- 17042500
TI  - Gene selection, alternative splicing, and post-translational processing regulate
      neuroligin selectivity for beta-neurexins.
AB  - Neuroligins 1-4 are postsynaptic transmembrane proteins capable of initiating
      presynaptic maturation via interactions with beta-neurexin. Both neuroligins and
      beta-neurexins have alternatively spliced inserts in their extracellular domains.
      Using analytical ultracentrifugation, we determined that the extracellular
      domains of the neuroligins sediment as dimers, whereas the extracellular domains
      of the beta-neurexins appear monomeric. Sedimentation velocity experiments of
      titrated stoichiometry ratios of beta-neurexin and neuroligin suggested a 2:2
      complex formation. The recognition properties of individual neuroligins toward
      beta-neurexin-1 (NX1beta), along with the influence of their splice inserts, were
      explored by surface plasmon resonance and affinity chromatography. Different
      neuroligins display a range of NX1beta affinities spanning more than 2 orders of
      magnitude. Whereas splice insert 4 in beta-neurexin appears to act only as a
      modulator of the neuroligin/beta-neurexin association, splice insert B in
      neuroligin-1 (NL1) is the key element regulating the NL1/NX1beta binding. Our
      data indicate that gene selection, mRNA splicing, and post-translational
      modifications combine to give rise to a controlled neuroligin recognition code
      with a rank ordering of affinities for particular neurexins that is conserved for
      the neuroligins across mammalian species.

PMID- 17042501
TI  - A single gamma-carboxyglutamic acid residue in a novel cysteine-rich secretory
      protein without propeptide.
AB  - Gamma-glutamyl carboxylase catalyzes the modification of specific glutamyl
      residues to gamma-carboxyglutamyl (Gla) residues in precursor proteins that
      possess the appropriate gamma-carboxylation recognition signal within the
      propeptide region. We describe the immunopurification and first biochemical
      characterization of an invertebrate high molecular weight Gla-containing protein
      with homologues in mammals. The protein, named GlaCrisp, was isolated from the
      venom of the marine cone snail Conus marmoreus. GlaCrisp gave intense signals in
      Western blot experiments employing the Gla-specific antibody M3B, and the
      presence of Gla was chemically confirmed by amino acid analysis after alkaline
      hydrolysis. Characterization of a full-length cDNA clone encoding GlaCrisp
      deduced a precursor containing an N-terminal signal peptide but, unlike other Gla
      containing proteins, no apparent propeptide. The predicted mature protein of 265
      amino acid residues showed considerable sequence similarity to the widely
      distributed cysteine-rich secretory protein family and closest similarity (65%
      identity) to the recently described substrate-specific protease Tex31. In
      addition, two cDNA clones encoding the precursors of two isoforms of GlaCrisp
      were identified. The predicted precursor isoforms differed at three amino acid
      positions (-6, 9, and 25). Analysis by Edman degradation and nanoelectrospray
      ionization mass spectrometry, before and after methyl esterfication, identified a
      Gla residue at amino acid position 9 in GlaCrisp. This is the first example of a
      Gla-containing protein without an obvious gamma-carboxylation recognition site.
      The results define a new class of Gla proteins and support the notion that gamma
      carboxylation of glutamyl residues is phylogenetically older than blood
      coagulation and the vertebrate lineage.

PMID- 17042502
TI  - Multiple interactions of FbsA, a surface protein from Streptococcus agalactiae,
      with fibrinogen: affinity, stoichiometry, and structural characterization.
AB  - Streptococcus agalactiae is an etiological agent of several infective diseases in
      humans. We previously demonstrated that FbsA, a fibrinogen-binding protein
      expressed by this bacterium, elicits a fibrinogen-dependent aggregation of
      platelets. In the present communication, we show that the binding of FbsA to
      fibrinogen is specific and saturable, and that the FbsA-binding site resides in
      the D region of fibrinogen. In accordance with the repetitive nature of the
      protein, we found that FbsA contains multiple binding sites for fibrinogen. By
      using several biophysical methods, we provide evidence that the addition of FbsA
      induces extensive fibrinogen aggregation and has noticeable effects on thrombin
      catalyzed fibrin clot formation. Fibrinogen aggregation was also found to depend
      on FbsA concentration and on the number of FbsA repeat units. Scanning electron
      microscopy evidentiated that, while fibrin clot is made of a fine fibrillar
      network, FbsA-induced Fbg aggregates consist of thicker fibers organized in a
      cage-like structure. The structural difference of the two structures was further
      indicated by the diverse immunological reactivity and capability to bind tissue
      type plasminogen activator or plasminogen. The mechanisms of FbsA-induced
      fibrinogen aggregation and fibrin polymerization followed distinct pathways since
      Fbg assembly was not inhibited by GPRP, a specific inhibitor of fibrin
      polymerization. This finding was supported by the different sensitivity of the
      aggregates to the disruptive effects of urea and guanidine hydrochloride. We
      suggest that FbsA and fibrinogen play complementary roles in contributing to
      thrombogenesis associated with S. agalactiae infection.

PMID- 17042503
TI  - Functional homodimers and heterodimers of recombinant smooth muscle tropomyosin.
AB  - Skeletal and smooth muscle tropomyosin (Tm) require acetylation of their N
      termini to bind strongly to actin. Tm containing an N-terminal alanine-serine
      (AS) extension to mimic acetylation has been widely used to increase binding. The
      current study investigates the ability of an N-terminal AS extension to mimic
      native acetylation for both alpha alpha and beta beta smooth Tm homodimers. We
      show that (1) AS alpha-Tm binds actin 100-fold tighter than alpha-Tm and 2-fold
      tighter than native smooth alphabeta-Tm, (2) beta-Tm requires an AS extension to
      bind actin, and (3) AS beta-Tm binds actin 10-fold weaker than AS alpha-Tm. Tm is
      present in smooth muscle tissues as >95% heterodimer; therefore, we studied the
      binding of recombinant alphabeta heterodimers with different AS extensions. This
      study shows that recombinant Tm requires an AS extension on both alpha and beta
      chains to bind like native Tm and that the alpha chain contributes more to actin
      binding than the beta chain. Once assembled onto an actin filament, all smooth
      muscle Tm's regulate S1 binding to actin Tm in the same way, irrespective of the
      presence of an AS extension.

PMID- 17042504
TI  - N-terminal fragments of tau inhibit full-length tau polymerization in vitro.
AB  - The polymerization of the microtubule-associated protein, tau, into insoluble
      filaments is a common thread in Alzheimer's disease and in a variety of
      frontotemporal dementias. The conformational change required for tau to
      transition from an extended monomeric state to a filamentous state with a high
      beta-sheet content involves the extreme N-terminus coming into contact with
      distal portions of the molecule; however, these exact interactions are
      incompletely understood. Here we report that a construct representing amino acids
      1-196 (Tau196), which itself does not polymerize, inhibits polymerization of full
      length tau (hTau40) in vitro. In addition, we trace the inhibitory effect of
      Tau196 to amino acids 18-42 of the construct. We also provide evidence that the N
      terminal tau fragments require a specific C-terminal region of tau (residues 392
      421) to exert their inhibitory effect. The fragments are most effective at
      inhibiting polymerization when present during the initial 5 min; they remain in
      the soluble fraction of the polymerization reaction, and they increase the amount
      of soluble hTau40. The fragments also reduce the number and average length of
      filaments that are formed. Taken together, these results suggest that the N
      terminal tau fragments inhibit hTau40 polymerization by interacting with a
      specific C-terminal sequence, thereby stabilizing a soluble conformation of tau.

PMID- 17042505
TI  - Characterization of the heme binding properties of Staphylococcus aureus IsdA.
AB  - We report the first characterization of the physical and spectroscopic properties
      of the Staphylococcus aureus heme-binding protein IsdA. In this study, a
      combination of gel filtration chromatography and analytical centrifugation
      experiments demonstrate that IsdA, in solution, is a monomer and adopts an
      extended conformation that would suggest that it has the ability to protrude from
      the staphylococcal cell wall and interact with the extracellular environment.
      IsdA efficiently scavenged intracellular heme within Escherichia coli. Gel
      filtration chromatography and electrospray mass spectrometry together showed that
      rIsdA in solution is a monomer, and each monomer binds a single heme. Magnetic
      circular dichroism analyses demonstrate that the heme in rIsdA is a five
      coordinate high-spin ferric heme molecule, proximally coordinated by a tyrosyl
      residue in a cavity that restricts access to small ligands. The heme binding is
      unlike that in a typical heme protein, for example, myoglobin, because we report
      that no additional axial ligation is possible in the high-spin ferric state of
      IsdA. However, reduction to ferrous heme is possible which then allows CO to
      axially ligate to the ferrous iron. Reoxidation forms the ferric heme, which is
      once again isolated from exogenous ligands. In summary, rIsdA binds a five
      coordinate, high-spin ferric heme which is proximally coordinated by tyrosine.
      Reduction results in formation of five-coordinate, high-spin ferrous heme with a
      neutral axial ligand, most likely a histidine. Subsequent addition of CO results
      in a six-coordinate low-spin ferrous heme also with histidine likely bound
      proximally. Reoxidation returns the tyrosine as the proximal ligand.

PMID- 17042506
TI  - Spectroscopic evidence for Ca2+ involvement in the assembly of the Mn4Ca cluster
      in the photosynthetic water-oxidizing complex.
AB  - Biogenesis and repair of the inorganic core (Mn4CaO(x)Cl(y)), in the water
      oxidizing complex of photosystem II (WOC-PSII), occurs through the light-induced
      (re)assembly of its free elementary ions and the apo-WOC-PSII protein, a reaction
      known as photoactivation. Herein, we use electron paramagnetic resonance (EPR)
      spectroscopy to characterize changes in the ligand coordination environment of
      the first photoactivation intermediate, the photo-oxidized Mn3+ bound to apo-WOC
      PSII. On the basis of the observed changes in electron Zeeman (g(eff)), 55Mn
      hyperfine (A(Z)) interaction, and the EPR transition probabilities, the
      photogenerated Mn3+ is shown to exist in two pH-dependent forms, differing in
      terms of strength and symmetry of their ligand fields. The transition from an EPR
      invisible low-pH form to an EPR-active high-pH form occurs by deprotonation of an
      ionizable ligand bound to Mn3+, implicated to be a water molecule: [Mn3+ (OH2)] <
      -> [Mn3+ (OH-)]. In the absence of Ca2+, the EPR-active Mn3+ exhibits a strong pH
      dependence (pH approximately 6.5-9) of its ligand-field symmetry (rhombicity
      Delta delta = 10%, derived from g(eff)) and A(Z) (DeltaA(Z) = 22%), attributable
      to a protein conformational change. Binding of Ca2+ to its effector site
      eliminates this pH dependence and locks both g(eff) and A(Z) at values observed
      in the absence of Ca2+ at alkaline pH. Thus, Ca2+ directly controls the
      coordination environment and binds close to the high-affinity Mn3+, probably
      sharing a bridging ligand. This Ca2+ effect and the pH-induced changes are
      consistent with the ionization of the bridging water molecule, predicting that
      [Mn3+-(mu-O(-2))-Ca2+] or [Mn3+-(mu-OH(-))2-Ca2+] is the first light intermediate
      in the presence of Ca2+. The formation of this intermediate templates the apo-WOC
      PSII for the subsequent rapid cooperative binding and photo-oxidation of three
      additional Mn2+ ions, forming the active water oxidase.

PMID- 17042507
TI  - A mass spectrometry-based probe of equilibrium intermediates in protein-folding
      reactions.
AB  - Described here is a mass spectrometry- and H/D exchange-based approach for the
      detection of equilibrium intermediate state(s) in protein-folding reactions. The
      approach utilizes the stability of unpurified proteins from rates of H/D exchange
      (SUPREX) technique to measure the m value (i.e., delta DeltaG/delta [denaturant]
      value) associated with the folding reaction of a protein. Such SUPREX m-value
      analyses can be made over a wide range of denaturant concentrations. Thus, the
      described approach is well-suited for the detection of high-energy intermediates
      that might be populated at low denaturant concentrations and hard to detect in
      conventional chemical denaturation experiments using spectroscopic probes. The
      approach is demonstrated on four known non-two-state folding proteins, including
      alpha-lactalbumin, cytochrome c, intestinal fatty acid binding protein (IFABP),
      and myoglobin. The non-two-state folding behavior of each model protein system
      was detected by the described method. The cytochrome c, myoglobin, and IFABP
      systems each had high-energy intermediate states that were undetected in
      conventional optical spectroscopy-based studies and previously required other
      more specialized biophysical approaches (e.g., nuclear magnetic resonance
      spectroscopy-based methods and protease protection assays) for their detection.
      The SUPREX-based approach outlined here offers an attractive alternative to these
      other approaches, because it has the advantage of speed and the ability to
      analyze both purified and unpurified protein samples in either concentrated or
      dilute solution.

PMID- 17042508
TI  - Replication-coupled repair of crotonaldehyde/acetaldehyde-induced guanine-guanine
      interstrand cross-links and their mutagenicity.
AB  - The repair of acetaldehyde/crotonaldehyde-induced guanine (N2)-guanine (N2)
      interstrand cross-links (ICLs), 3-(2-deoxyribos-1-yl)-5,6,7,8-(N2-deoxyguanosyl)
      6(R or S)-methylpyrimido[1,2-alpha]purine-10(3H)-one, was studied using a shuttle
      plasmid bearing a site-specific ICL. Since the authentic ICLs can revert to
      monoadducts, a chemically stable model ICL, 1,3-bis(2'-deoxyguanos-N2-yl)butane
      derivative, was also employed to probe the ICL repair mechanism. Since the
      removal of ICL depends on the nucleotide excision repair (NER) mechanism in
      Escherichia coli, the plasmid bearing the model ICL failed to yield transformants
      in NER-deficient host cells, proving the stability of this ICL in cells. The
      authentic ICLs yielded transformants in the NER-deficient hosts; therefore, these
      transformants are produced by plasmid bearing spontaneously reverted monoadducts.
      In contrast, in NER-deficient human cells, the model ICL was removed by an NER
      independent repair pathway, which is unique to higher eukaryotes. This repair did
      not associate with a transcriptional event, but with replication. The analysis of
      repaired molecules revealed that the authentic and model ICLs were repaired
      mostly (>94%) in an error-free manner in both hosts. The major mutations that
      were observed were G --> T transversions targeting the cross-linked dG located in
      the lagging strand template. These results support one of the current models for
      the mammalian NER-independent ICL repair mechanism, in which a DNA
      endonuclease(s) unhooks an ICL from the leading strand template at a stalled
      replication fork site by incising on both sides of the ICL and then translesion
      synthesis is conducted across the "half-excised" ICL attached to the lagging
      strand template to restore DNA synthesis.

PMID- 17042509
TI  - Potent lectin-independent chaperone function of calnexin under conditions
      prevalent within the lumen of the endoplasmic reticulum.
AB  - Calnexin is a membrane-bound chaperone of the endoplasmic reticulum (ER) that
      participates in the folding and quality control of newly synthesized
      glycoproteins. Binding to glycoproteins occurs through a lectin site with
      specificity for Glc1Man9GlcNAc2 oligosaccharides as well as through a polypeptide
      binding site that recognizes non-native protein conformations. The latter
      interaction is somewhat controversial because it is based on observations that
      calnexin can suppress the aggregation of non-glycosylated substrates at elevated
      temperature or at low calcium concentrations, conditions that may affect the
      structural integrity of calnexin. Here, we examine the ability of calnexin to
      interact with a non-glycosylated substrate under physiological conditions of the
      ER lumen. We show that the soluble ER luminal domain of calnexin can indeed
      suppress the aggregation of non-glycosylated firefly luciferase at 37 degrees C
      and at the normal resting ER calcium concentration of 0.4 mM. However, gradual
      reduction of calcium below the resting level was accompanied by a progressive
      loss of native calnexin structure as assessed by thermal stability, protease
      sensitivity, intrinsic fluorescence, and bis-ANS binding. These assays permitted
      the characterization of a single calcium binding site on calnexin with a Kd =
      0.15 +/- 0.05 mM. We also show that the suppression of firefly luciferase
      aggregation by calnexin is strongly enhanced in the presence of millimolar
      concentrations of ATP and that the Kd for ATP binding to calnexin in the presence
      of 0.4 mM calcium is 0.7 mM. ATP did not alter the overall stability of calnexin
      but instead triggered the localized exposure of a hydrophobic site on the
      chaperone. These findings demonstrate that calnexin is a potent molecular
      chaperone that is capable of suppressing the aggregation of substrates through
      polypeptide-based interactions under conditions that exist within the ER lumen.

PMID- 17042510
TI  - On the stability of miniemulsions in the presence of RAFT agents.
AB  - The colloidal stability of miniemulsions in the presence of RAFT or other control
      agents for controlled free radical polymerization is examined. A derivation,
      based on Lifshitz-Slyozov-Wagner (LSW) theory, is proposed here to evaluate the
      effect of a RAFT agent on the diffusional stability of the miniemulsions before
      the onset of polymerization. Results indicate that, depending on the
      hydrophobicity of the control agent, its presence may augment or detract from the
      effectiveness of the costabilizer in preventing diffusional instability due to
      Ostwald ripening.

PMID- 17042511
TI  - Surface-enhanced Raman scattering on molecular self-assembly in nanoparticle
      hydrogel composite.
AB  - Surface-enhanced Raman scattering has been applied to study weak intermolecular
      interactions between small organic gelling molecules involved in the silver
      nanoparticle-hydrogel composite formation. Assembly and disassembly of the
      gelator molecules in close vicinity to embedded silver nanoparticles were
      followed by changes in Raman intensity of the amide II and carboxyl vibrational
      bands, whereas the strength of the bands related to benzene modes remained
      constant. This implied that the gelator molecules were strongly attached to the
      silver particles through the benzene units, while participating in gel structure
      organization by intermolecular hydrogen bonding between oxalyl amide and carboxyl
      groups.

PMID- 17042512
TI  - Molecular dynamics investigation of bent-core molecules on a water surface.
AB  - Molecular dynamics simulations are carried out for bent-core molecules at water
      surfaces. The water surface is shown to alter the equilibrium molecular structure
      significantly by causing a different class of torsional states to become more
      favorable. The equilibrium structure is also altered by the substitution of
      chlorine atoms for hydrogen atoms on the central phenyl ring in that this
      substitution forces the bent core to remain in a single torsional state rather
      than be delocalized among several torsional states. The consequences of these
      structural changes on the chirality and packing of these molecules on water
      surfaces are discussed.

PMID- 17042513
TI  - Electrochemical capacitances of well-defined carbon surfaces.
AB  - Reported is the capacitive behavior of homogeneous and well-defined surfaces of
      pristine carbon nanofibers (CNFs) and surface-modified CNFs. The capacitances of
      the well-defined CNFs were measured with cyclic voltammetry to correlate the
      surface structure with capacitance. Among the studied pristine CNFs, the edge
      surfaces of platelet CNFs (PCNF) and herringbone CNFs were more effective in
      capacitive charging than the basal plane surface of tubular CNF by a factor of 3
      5. Graphitization of PCNF (GPCNF) changed the edge surface of PCNF into a
      domelike basal plane surface, and the corresponding capacitances decreased from
      12.5 to 3.2 F/g. A chemical oxidation of the GPCNF, however, recovered a clear
      edge surface by removal of the curved basal planes to increase the capacitance to
      5.6 F/g. The difference in the contribution of the edge surface and basal-plane
      surface to the capacitance of CNF was discussed in terms of the anisotropic
      conductivity of graphitic materials.

PMID- 17042514
TI  - Patterning amyloid peptide fibrils by AFM charge writing.
AB  - Surface charge patterns generated by atomic force microscopy-based charge writing
      were used to pattern amyloid-like peptide fibrils on a solid substrate. Fibrils
      of the short peptide TTR105-115 were encapsulated inside water droplets of a
      water-in-perfluorocarbon oil emulsion and retained their rod morphology. They
      were observed to deposit selectively with a lateral resolution of approximately 1
      microm onto negatively charged patterns on a polymethyl-methacrylate substrate.

PMID- 17042515
TI  - Biomimetic growth of silica tubes in confined media.
AB  - Polymer membranes were used as biomimetic environments to study the effect of
      confinement on silica formation. Within membrane pores, silica tubes were formed,
      consisting of a dense silica shell incorporating nanoparticle aggregates. The
      shell structure does not depend on the membrane pore size, suggesting that its
      formation proceeds via interfacial interactions with the pore surface. In
      contrast, the size of primary nanoparticles within core aggregates is influenced
      by pore dimensions, indicating an effect of confinement on the diffusion-limited
      growth of silica. A parallel can be drawn with reported roles of confinement in
      biomineralization processes, providing a basis for future developments in
      biosilicification mimetic approaches and biofunctional nanomaterials design.

PMID- 17042516
TI  - Lipid diffusion in giant unilamellar vesicles is more than 2 times faster than in
      supported phospholipid bilayers under identical conditions.
AB  - The lateral diffusion coefficients of a BODIPY tail-labeled lipid in two model
      systems, namely, free-standing giant unilamellar vesicles (GUVs) and supported
      phospholipid bilayers (SPBs), were determined by fluorescence correlation
      spectroscopy (FCS) using the Z-scan approach. For the first time, the performed
      measurements on 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers maintain
      exactly the same experimental conditions for both systems, which allows for a
      quantitative comparison of lipid diffusion in these two commonly used model
      membranes. The results obtained revealed that the lipid mobility in free-standing
      bilayers (D=7.8+/-0.8 microm2 s-1) is significantly higher than in the bilayer
      created on the solid support (mica) (D=3.1+/-0.3 microm2 s-1).

PMID- 17042517
TI  - Supramolecular dynamics studied using photophysics.
AB  - Dynamics is an essential feature of supramolecular systems, and it's
      understanding will be central in achieving new chemical function. The methodology
      to obtain association and dissociation rate constants for fast binding of guests
      to host systems in real time is described. Examples are provided for binding of
      guests to cyclodextrins or bile salt aggregates with an emphasis on the type of
      information and mechanistic insight that can only be uncovered from kinetic
      studies and is not apparent in thermodynamic investigations.

PMID- 17042518
TI  - Effect of surfactant conformation on the structures of small size nonionic
      reverse micelles: a molecular dynamics simulation study.
AB  - We used constant pressure (P=0.1 MPa) and temperature (T=298 K) molecular
      dynamics simulations to study the structures and dynamics of small size reverse
      micelles (RMs) with poly(ethylene glycol) alkyl ether (CmEn) surfactants. The
      water-to-surfactant molar ratio was 3, with decane as the apolar solvent. We
      focused on the effect of the two possible imposed conformations (trans vs gauche)
      for the surfactant headgroups on RMs structures and water dynamics. For this
      purpose, we built up two RMs, which only differ by their surfactant headgroup
      conformations. The results obtained for the two RMs were compared to what is
      known in the literature. Here, we show that the surfactant headgroup conformation
      affects mainly the water-related properties such as the water core size, the area
      per surfactant headgroup, the headgroup hydration, and the water core
      translational diffusion. The properties computed for the RM with the surfactant
      in trans conformation fit better with the experimental data than the gauche
      conformation. We further show that the surfactant hydrophilic headgroup plays a
      crucial role in the micellar structures, favors the entrapment of the micellar
      water, and reduces strongly their diffusion compared to the bulk water.

PMID- 17042519
TI  - Depletion interaction mediated by a polydisperse polymer studied with total
      internal reflection microscopy.
AB  - Total internal reflection microscopy (TIRM) was applied to measure depletion
      forces between a charged colloidal sphere and a charged solid wall induced by
      dextran, a nonionic nonadsorbing polydisperse polysaccharide. The polymer size
      polydispersity is shown to greatly influence the depletion potential. Using the
      theory for the depletion interaction due to ideal polydisperse polymer chains, we
      could accurately describe the experimental data with a single adjustable
      parameter.

PMID- 17042520
TI  - Clouding and phase behavior of nonionic surfactants in hydrophobically modified
      hydroxyethyl cellulose solutions.
AB  - Clouding phenomena and phase behaviors of two nonionic surfactants, Triton X-114
      and Triton X-100, in the presence of either hydroxyethyl cellulose (HEC) or its
      hydrophobically modified counterpart (HMHEC) were experimentally studied.
      Compared with HEC, HMHEC was found to have a stronger effect on lowering the
      cloud point temperature of a nonionic surfactant at low concentrations. The
      difference in clouding behavior can be attributed to different kinds of molecular
      interactions. Depletion flocculation is the underlying mechanism in the case of
      HEC, while the chain-bridging effect is responsible for the large decrease of
      cloud point for HMHEC. Composition analyses for the formed macroscopic phases
      were carried out to provide support for associative phase separation for the case
      of HMHEC, in contrast to segregative phase separation for HEC. An interesting
      three-phase-separation phenomenon was reported in some HMHEC/Triton X-100
      mixtures at high surfactant concentrations.

PMID- 17042521
TI  - Fabrication of colloidal doublets by a salting out-quenching-fusing technique.
AB  - It is well-known that high ionic strength promotes colloid aggregation. Here we
      show that, by controlling this aggregation process, we can produce high yields of
      homodoublet and heterodoublet polymer colloids. The aggregation process is
      started by increasing the ionic strength to roughly 250 mM KCl. After
      approximately the rapid flocculation time, we quench the "reaction" by mixing in
      a large quantity of deionized water, which dilutes the ionic strength and
      prevents further aggregation. At this point, the suspension consists primarily of
      singlet and doublet particles. Through heating above the glass transition
      temperature of the polymers, the doublets are fused together and remain intact
      even after sonication. It is also shown that heterodoublets can include a silica
      particle together with a polymer colloid. The salting out-quenching-fusing
      technique is a rapid, easy-to-perform, repeatable process for fabricating
      colloidal doublets from polymers and other materials.

PMID- 17042522
TI  - Diffusion of platinum ions and platinum nanoparticles during photoreduction
      processes using the transient grating method.
AB  - The photoreduction process of PtCl(6)2- to Pt nanoparticles in poly(N-vinyl-2
      pyrrolidone) solutions upon UV light irradiation was investigated by monitoring
      the change in the diffusion coefficient (D). The D values of chemical species
      during UV irradiation was measured by the laser-induced transient grating (TG)
      method. The TG signal of the PtCl(6)2- solution before UV irradiation was
      composed of three kinds of contributions, the thermal grating, the species
      grating due to the creation of PtCl4(2-), and the species grating due to the
      depletions of PtCl6(2-). Upon UV irradiation of the solution, the species grating
      signal due to PtCl6(2-) diminished and then the TG signal of Pt nanoparticles
      gradually appeared. This result indicates that the gradual clustering of Pt0
      atoms into Pt nanoparticles occurs after all PtCl(6)2- ions are photochemically
      reduced to PtCl(4)2- and subsequently transformed to Pt0 atoms with a short
      delay. With increasing time of the UV irradiation, the TG signal intensity
      increased, while D of the Pt nanoparticles did not change. This suggests that the
      number of Pt nanoparticles increases, but the size of the Pt nanoparticles with
      the polymer layer is unchanged, in the course of the UV irradiation.

PMID- 17042523
TI  - Electrostatically driven protein aggregation: beta-lactoglobulin at low ionic
      strength.
AB  - The aggregation of beta-lactoglobulin (BLG) at ambient temperature was studied
      using turbidimetry and dynamic light scattering in the range 3.8<pH<5.2 in 0.0045
      M NaCl, and in the ionic strength range 0.0045-0.5 M at fixed pH=5.0. The initial
      rate of aggregation, taken as the initial slope of turbidity vs time, (dtau/dt)0,
      indicated maximum aggregation near pH 4.6 (below the isoelectric point of 5.2),
      but the dependence of the initial rate of aggregation on pH was highly
      asymmetric. At pH 5.0, (dtau/dt)0 strongly increased with a decrease in ionic
      strength I from 0.1 to 0.0045 M and was found to be nearly linear with 1/I. DLS
      measurements revealed an increase in particle size with time, with the appearance
      of bimodal distributions in which the fast and slow modes corresponded,
      respectively, to a BLG dimer and to larger aggregates in the 100-800 nm range. At
      conditions of slower aggregation, DLS revealed the consumption of dimers to form
      higher order aggregates with no intermediate species. Computer modeling (Delphi)
      was used to visualize the electrostatic potential around the dimer to elucidate
      the pH and ionic strength dependence of the initial aggregation rates. The
      aggregation process appears to comprise an initial fast consumption of the dimer,
      whose dependence on pH and I arises from the interaction of the positive and
      negative domains of interacting dimers, followed by the slow formation of much
      larger aggregates with relatively little sensitivity to pH and I. The open-ended
      nature of BLG aggregation is thought to arise from the asymmetry of the dimer
      charge distribution.

PMID- 17042524
TI  - Dynamic light scattering, interfacial properties, and conformational analysis of
      biodegradable quarternary ammonium surfactants.
AB  - Aggregation properties of biodegradable ammonium surfactants containing amide and
      ester groups in the bulk and at the air-water interface were investigated as a
      function of surfactant tail length m using dynamic light scattering and surface
      tension experimental methods. The results indicate that surfactants containing an
      ester group in the structure display higher aggregation ability in the volume and
      form more densely packed layer of molecules at the air-water interface than those
      with an amide group. The results of physical measurements were correlated with 3D
      models of respective surfactant molecules. As the results indicate, a surfactant
      molecule headgroup containing an ester group shows higher flexibility than that
      with an amide group in its structure, which is documented by somewhat smaller
      headgroup size and denser packing at the air-water interface.

PMID- 17042525
TI  - Interfacial behavior of cubic liquid crystalline nanoparticles at hydrophilic and
      hydrophobic surfaces.
AB  - The adsorption behavior of self-assembled lipid liquid crystalline nanoparticles
      at different model surfaces was investigated in situ by use of ellipsometry. The
      technique allows time-resolved monitoring of the adsorbed amount and layer
      thickness under transient and steady-state conditions. The system under study was
      cubic-phase nanoparticle (CPNP) dispersions of glycerol monooleate stabilized by
      a nonionic block copolymer, Pluronic F-127. Depending on the surface properties
      and presence of electrolytes, different adsorption scenarios were discerned: At
      hydrophilic silica thick surface layers of CPNPs are generated by particle
      adsorption from dispersions containing added electrolyte, but no adsorption is
      observed in pure water. Adsorption at the hydrophobic surface involves extensive
      structural relaxation and formation, which is not electrolyte sensitive, of a
      classic monolayer structure. The different observations are rationalized in terms
      of differences in interactions among the CPNP aggregates, their unimer
      constituents, and the surface and show a strong influence of interfacial
      interactions on structure formation. Surface self-assembly structures with
      properties similar to those of the corresponding bulk aggregates appear
      exclusively in the weak interaction limit. This observation is in agreement with
      observations for surfactant self-assembly systems, and our findings indicate that
      this behavior is applicable also to complex self-assembly structures such as the
      CPNP structures discussed herein.

PMID- 17042526
TI  - Effect of temperature and surfactant structure on the microviscosity at the
      micelle-water interface: isomeric alkylbenzenesulfonates used as their own probe.
AB  - We investigated the effect of temperature and surfactant structure on the
      microviscosity in aqueous micellar solutions formed by isomeric
      hexadecylbenzenesulfonates (xphiC16, where x=4-6 and indicates the position of
      the benzene ring [phi] along the alkyl chain) by fluorescence polarization and
      excimer emission spectroscopy. For a given isomer, the degree of polarization (p)
      was found to decrease with increasing temperature, with no evidence for changes
      in micellar structure. etaint/tau ratios, where etaint is the microviscosity of
      the benzene environment in micelles and tau its natural lifetime, were derived
      from fluorescence polarization measurements and showed a similar temperature
      behavior to that observed with the degree of polarization, suggesting that a
      thermal effect is the determinant factor in the variation of etaint.
      Interestingly, the microviscosity around the benzene ring was found to depend on
      the isomer structure in the entire range of temperatures investigated (8-60
      degrees C) and is mainly determined by the orientation of the surfactant at the
      micelle-water interface in which the short alkyl chain is preferentially located
      at the interface and the long alkyl chain in the micellar core. This micelle
      conformation was found to prevail in the entire range of temperatures. In
      contrast to the dependence of p with temperature, excimer to monomer maximum
      emission ratios (IE/IM) were found to increase with increasing temperature,
      showing that when IE/IM is high (strong excimer emission), the degree of
      polarization is low (low microviscosity) and vice versa. Thus, the two
      independent measurements (IE/IM and p) yield the same information, namely, that
      the benzene moiety in all xphiC16 aqueous micelles resists both translational and
      rotational diffusion in a similar manner in the entire range of temperatures
      investigated (approximately 8-60 degrees C).

PMID- 17042527
TI  - Water-soluble hydrogen-bonding interpolymer complex formation between
      poly(ethylene glycol) and poly(acrylic acid) grafted with poly(2-acrylamido-2
      methylpropanesulfonic acid).
AB  - Comb-type copolymers of poly(acrylic acid) grafted with poly(2-acrylamido-2
      methylpropanesulfonic acid) (PAMPSA) side chains form with poly(ethylene glycol),
      at low pH, water-soluble hydrogen-bonding interpolymer complexes. Turbidimetry,
      viscometry, and dynamic light scattering measurements suggest that compact,
      negatively charged, colloidal nanoparticles are formed at pH<3.75. The influence
      of the structure of the graft copolymers and of the ionic strength of the
      solution on the size of these nanoparticles was investigated. It was found that
      their hydrodynamic radius decreases by increasing the molecular mass of the
      PAMPSA side chains of the graft copolymer and increases with increasing the ionic
      strength of the solution.

PMID- 17042528
TI  - Adsorption and aggregation properties of heterogemini surfactants containing a
      quaternary ammonium salt and a sugar moiety.
AB  - A novel heterogemini surfactant comprising two hydrocarbon chains and two
      different hydrophilic groups such as a quaternary ammonium cation and gluconamide
      nonion N,N-dimethyl-N-[2-(N'-alkyl-N'-gluconamide)ethyl]-1-alkylammonium bromides
      (2CnAmGlu, where n represents hydrocarbon chain lengths of 8, 10, 12, and 14) was
      synthesized by reacting N,N-dimethylethylenediamine with alkyl bromide, followed
      by a reaction with 1,5-D(+)-gluconolactone. The adsorption properties of 2CnAmGlu
      were characterized by surface tension measurements made using the Wilhelmy plate
      method, and their aggregation properties were investigated by dynamic light
      scattering and cryogenic transmission electron microscopy techniques. The
      relationship between the hydrocarbon chain length and the logarithm of the
      critical micelle concentration (cmc) for 2CnAmGlu exhibited a linear decrease
      when the chain length was increased up to 12 and then a departure from linearity
      at n=14. The surface tension reached 24-26 mN m-1 at each cmc, indicating high
      efficiency in lowering the surface tension of water. Furthermore, it was found
      that the structure of the aggregate formed for 2CnAmGlu in solution was
      influenced by the hydrocarbon chain length; that is, for n=10 and 12, micelles
      with a hydrodynamic radius of 2-5 nm were formed, whereas vesicles were also
      observed for n=14.

PMID- 17042529
TI  - Diblock copolymer surfactant transport across the interface between two
      homopolymers.
AB  - Dynamics of adsorption and desorption of a diblock copolymer to an interface
      between two homopolymers was measured using dynamic secondary-ion mass
      spectrometry (SIMS). Thin films were constructed consisting of a layer of
      saturated polybutadiene with 90% 1,2-addition (sPB90), followed by a layer of
      saturated polybutadiene with 63% 1,2-addition (sPB63), and finally by another
      layer of the sPB90 homopolymer. A sPB90-sPB63 diblock copolymer was initially
      included only in the top sPB90 layer of the film at a volume fraction of 0.05.
      The thin films were annealed at ambient temperature for times ranging between 0.2
      and 108 h, and the concentration profiles of the diblock copolymer through the
      films were measured using SIMS. The dynamics of adsorption and desorption of the
      diblock copolymer at the two sPB90-sPB63 interfaces was gauged by comparing the
      different transient concentration profiles. The sorption process was modeled as
      diffusion in an external field, generated from self-consistent field theory
      (SCFT). All parameters for the model were determined independently. Although the
      model neglects the dynamics of conformational change, experimental results
      matched theory very well.

PMID- 17042530
TI  - Relationship between macroscopic and microscopic models of surfactant adsorption
      dynamics at fluid interfaces.
AB  - In a companion preceding paper, we presented an experimental investigation into
      the adsorption dynamics of a diblock copolymer surfactant to a polymer/polymer
      interface and found them to be well-described by a microscopic model of diffusion
      in a potential generated using self-consistent field theory. We compare the
      predictions of the microscopic approach with a macroscopic (adsorption-diffusion)
      model and demonstrate the equivalence of the two models when the free-energy well
      underlying surfactant adsorption is flanked by barriers that are significantly
      larger than thermal energy (kT). However, when the energy barriers are
      nonexistent, as is the case for the experimental system of interest, a finite
      interfacial width must be introduced into the classical model to obtain
      physically meaningful results (i.e., nonnegative desorption rates). Surprisingly,
      we find that the predictions of the macroscopic finite interfacial width model
      with no adjustable parameters are in excellent agreement with experimental data
      presented in the companion paper even though the latter was obtained with
      molecular resolution. This agreement provides insight into aspects of the free
      energy landscape that determine surfactant transport.

PMID- 17042531
TI  - Structures of palmitoyl-L and DL-lysine monolayers at the air-water interface-
      polarization modulation infrared reflection absorption spectroscopic study.
AB  - Polarization modulation infrared reflection absorption spectroscopy (PM-IRAS) was
      applied to measure the IR spectra of palmitoyl-DL-lysine (L-PL) and palmitoyl-DL
      lysine (DL-PL) at the air-water interface. The spectra in the amide I and II
      regions were simulated by using the extinction coefficients of the amide I and II
      bands of L-PL and DL-PL determined by the analyses of the IR external reflection
      spectra of the Langmuir-Blodget (LB) films prepared on a Ge plate (Yasukawa et
      al. J. Mol. Struct. 2005, 735-736, 53), indicating the angle between the plane of
      the secondary amide group (the amide plane) and the surface normal in the L-PL
      monolayer to be about 20 degrees and the angle in the DL-PL monolayer to be about
      37 degrees. Comparison of the tilt angles with the corresponding angles in the LB
      films (about 20 degrees for the LB film of L-PL; about 49 degrees for the LB film
      of DL-PL) indicated that, upon being transferred to the solid substrate from the
      air-water interface, the L-PL monolayer keeps the orientation of the amide plane
      virtually unchanged, while the DL-PL monolayer changes the orientation
      appreciably to a horizontal direction. The orientation change of the amide plane
      was interpreted as due to the accommodation of irregularly oriented palmitoyl
      groups into the LB films of DL-PL on the solid substrate.

PMID- 17042532
TI  - Characterization of Pd-Cu alloy nanoparticles on gamma-Al2O3-supported catalysts.
AB  - Cu-Pd/Al2O3 bimetallic catalysts have been characterized by XRD, TEM, and EDX
      techniques. The surface structure has been investigated by FT-IR spectroscopy of
      low-temperature adsorbed CO in the reduced and in the oxidized state. Evidence
      has been provided of the formation of Cu-Pd alloy nanoparticles, both of the
      alpha-phase (disordered fcc) and of the beta-phase (ordered CsCl-type). IR
      spectra suggest that Cu likely decorates the edges while Pd mostly stays at the
      main faces. Part of copper disperses as Cu+ on the support even after reduction.
      The presence of copper seems to modify strongly the sate of oxidized Pd centers
      in oxidized high-Pd content materials. The redox chemistry of the system, where
      Pd is reduced more easily than Cu, appears to be very complex.

PMID- 17042533
TI  - Change in desorption mechanism from pore blocking to cavitation with temperature
      for nitrogen in ordered silica with cagelike pores.
AB  - To verify pore blocking controlled desorption in ink-bottle pores, we measured
      the temperature dependence of the adsorption-desorption isotherms of nitrogen on
      four kinds of KIT-5 samples with expanded cavities hydrothermally treated for
      different periods of time at 393 K. In the samples, almost spherical cavities are
      arranged in a face-centered cubic array and the cavities are connected through
      small channels. The pore size of the channels increased with an increase in the
      hydrothermal treatment time. At lower temperatures a steep desorption branch
      changed to a gradual one as the hydrothermal treatment was prolonged. For the
      sample hydrothermally treated only for 1 day, the rectangular hysteresis loop
      shrank gradually with increasing temperature while keeping its shape. The
      temperature dependence of the evaporation pressure observed was identical with
      that expected for cavitation-controlled desorption. On the other hand, for the
      samples hydrothermally treated for long times, the gradual desorption branch
      became a sharp one with increasing temperature. This strongly suggests that the
      desorption mechanism is altered from pore blocking to cavitation with
      temperature. Application of percolation theory to the pore blocking controlled
      desorption observed here is discussed.

PMID- 17042534
TI  - Contact studies of weakly compressed PEG brushes with a quartz crystal resonator.
AB  - A quartz crystal resonator was used to characterize the contact of an elastomeric
      polymer membrane with a grafted poly(ethylene glycol) (PEG) brush in an aqueous
      environment. A two-layer model of the acoustic impedance of the system was used
      to measure the brush thickness before and after contact with the membrane. This
      model was further extended to include multiple layers, allowing characterization
      of other monomeric density profiles along the brush thickness. The polymer brush
      maintains a hydrated layer between the membrane and the quartz crystal surface,
      the thickness of which could be determined to within 1 nm. We show that the
      technique is very well suited for studying the properties of highly hydrated
      layers with thicknesses between 0 and 100 nm at low contact pressures
      corresponding to a very weak compression of the PEG brush.

PMID- 17042535
TI  - Density variation-induced sign change of the effective hamaker constant in
      continuum theory.
AB  - The density variation-induced dewetting model is reformulated in terms of the
      Dzyaloshinskii-Lifshitz-Pitaevskii continuum theory for van der Waals
      interactions. Though the density dependence is more complicated than in the
      London-Hamaker microscopic theory, numerical calculations for model polystyrene
      films show that the two theories yield qualitatively similar results. The physics
      of the dewetting model is thus not changed. Quantitatively, the differences
      between the two theories are notable. The calculations also show that a linear
      approximation suffices to take density variations into account, thus simplifying
      the density variation-induced dewetting models.

PMID- 17042536
TI  - Removal of induced nanobubbles from water/graphite interfaces by partial
      degassing.
AB  - Nanobubbles at an interface between a hydrophobic solid and water have a wide
      range of implications, but the evidence for their existence is still being
      debated. Here we artificially induced nanobubbles on freshly cleaved HOPG
      substrates in water using the protocol developed previously and subjected the
      system to moderate levels of degassing (approximately 0.1 atm for 0.5 to 3 h).
      The AFM images after the partial degassing revealed that some nanobubbles had
      coalesced and detached from the substrate because of buoyancy, whereas others
      apparently remained unaffected. The size and spatial distributions of the
      nanobubbles after the partial degassing suggest that there is a critical size for
      a nanobubble above which it may grow. The contact angle of water next to
      nanobubbles (approximately 160 degrees) is much larger than the advancing contact
      angle of a macroscopic water droplet on the same substrate (approximately 80
      degrees) both before and after the partial degassing and concomitant growth and
      shrinkage of the nanobubbles. The contact angle of a nanobubble also remained
      unchanged as the nanobubble was moved along the substrate by the AFM tip. The
      apparent lack of contact angle hysteresis in the nanobubble systems may suggest
      that the very large contact angle may correspond to a local minimum of the free
      energy landscape.

PMID- 17042537
TI  - ToF-SIMS investigation of octadecylphosphonic acid monolayers on a mica
      substrate.
AB  - In this paper, time-of-flight secondary ion mass spectrometry (ToF-SIMS) under
      static conditions was used to investigate self-assembled monolayers (SAMs) of
      octadecylphosphonic acid (OPA) formed on freshly cleaved muscovite mica
      substrates. The coverage of OPA on mica ranged from 20 to 100%, with a film
      thickness of 1.7+/-0.2 nm, which was determined by atomic force microscopy (AFM)
      imaging. The relative intensity of the specific secondary ion species associated
      with the OPA and with the exposed mica substrate exhibited good correlation with
      surface coverage. An excellent correlation was also observed (R2=0.98) between
      the relative SIMS [OPA-H]- intensity and the surface carbon concentration (OPA C
      1s, in atomic %) from XPS at the prescribed surface coverage. The observation of
      positive and negative OPA molecular attachment of secondary ions involving the
      substrate species is discussed in terms of the chemical affinity of the OPA
      phosphonate headgroup for the cleaved mica surface as well as the sampling depth.
      In addition, the OPA molecular attachment species formed with the potassium ions
      on the cleaved mica substrate dominated the positive secondary ion mass spectrum
      in the high-mass range. A temperature-dependent, ToF-SIMS study employing in situ
      heating of a 100% coverage OPA monolayer revealed that the molecules begin to
      diffuse above approximately 80 degrees C, resulting in a decrease in the relative
      secondary ion yield of the OPA-specific secondary ions. This observation is
      hypothesized to be due to a decrease in the effective coverage of the substrate
      by the OPA molecules, which in turn could be due to the formation of multilayers
      upon heating in an effort to minimize the energy of the system. The interesting
      behavior of the novel OPA dimer species as a function of temperature is also
      reported. It was observed that the relative intensity of OPA and the mica
      specific secondary ion peak intensities to that of Si (mica substrate) provides
      an effective means to estimate the change in coverage at elevated temperatures.

PMID- 17042538
TI  - Anomalous sorption of supercritical fluids on polymer thin films.
AB  - Unusual sorption has been reported in thin polymer films exposed to near-critical
      CO2. When the supercritical fluid approaches the critical point, the film appears
      to thicken, but it is not clear whether the film swells or there is an adsorption
      layer on the film surface. A combination of the gradient theory of inhomogeneous
      systems and the Sanchez-Lacombe equation of state has been used to investigate
      this phenomenon. It is shown analytically that surface adsorption on an
      attractive surface is proportional to the compressibility of the fluid. We have
      also investigated numerically the sorption of supercritical CO2 on
      poly(dimethylsiloxane) and polyisobutylene, and supercritical 1,1-difluoroethane
      on polystyrene. By calculating the Gibbs adsorption and adsorption layer
      thickness of the supercritical fluids, we found in all cases (different
      substrates, different supercritical fluids) that maximum adsorption occurs when
      the supercritical fluid is near its compressibility maximum.

PMID- 17042539
TI  - Friction force microscopy of alkylphosphonic acid and carboxylic acids adsorbed
      on the native oxide of aluminum.
AB  - Monolayers of alkylphosphonic acids (APA) and alkylcarboxylic acids (ACA) on
      magnetron-sputtered aluminum films have been investigated by friction force
      microscopy (FFM), contact angle measurement, and polarization-modulation infrared
      reflection-absorption spectroscopy (PM-IRRAS). Clear evidence has been provided
      from PM-IRRAS that friction coefficients, determined from FFM data, may be
      correlated directly with variations in adsorbate molecular structure. The
      friction coefficient increased with the length of the adsorbate molecule, but
      reached a limiting value when the alkyl chain of the adsorbate contained eight
      carbons in the case of APA or 12 carbons in the case of ACA. For a given alkyl
      chain length, APA monolayers yielded coefficients of friction that were similar
      to those of monolayers of alkylthiols of the same length, but smaller than those
      of ACA. These data indicate that APA monolayers are better ordered than ACA
      monolayers. These inferences were supported by PM-IRRAS data, which enabled the
      density of gauche defects to be estimated and correlated with variations in the
      coefficient of friction.

PMID- 17042540
TI  - Self-assembly of tin oxide nanoparticles: localized percolating network formation
      in polymer matrix.
AB  - A novel method to prepare transparent antistatic films by trapping nanoparticles
      in thin surface layers is proposed, and high performance of the product is
      demonstrated. Coating solutions consisting of surface-active antimony-doped tin
      oxide (ATO) nanoparticles, an organic solvent mixture of high affinity with
      poly(methyl methacrylate) substrate, and an ultraviolet curable resin are used
      for the film formation. Antistatic property of the layer is obtained at ATO
      concentrations above the critical concentration for percolation. A scaling
      analysis of the data shows that the critical concentration (0.004 volume
      fraction) is extremely low as compared to the value predicted by the percolation
      theory for randomly packed systems as well as the values in ever developed
      composite films filled with ATO particles. Microscopic observation of the
      deposited layers indicates that percolating clusters of ATO particles are
      localized on the layer surfaces. The excellent electrical and optical properties
      of the layer are attributed to the characteristic microstructure.

PMID- 17042541
TI  - Langmuir and Langmuir-Blodgett films of poly(ethylene oxide)-b-poly(epsilon
      caprolactone) star-shaped block copolymers.
AB  - Self-assembly of poly(ethylene oxide)-block-poly(epsilon-caprolactone) five-arm
      stars (PEO-b-PCL) was studied at the air/water (A/W) interface. The block
      copolymers consist of a hydrophilic PEO core with hydrophobic PCL chains at the
      star periphery. All the polymers have the same number of ethylene oxide repeat
      units (9 per arm), and the number of epsilon-caprolactone repeat units ranges
      from 0 to 18 per arm. The Langmuir monolayers were analyzed by surface
      pressure/mean molecular area isotherms, compression-expansion hysteresis
      experiments, and isobaric relaxation measurements, and the Langmuir-Blodgett (LB)
      films' morphologies were investigated by atomic force microscopy (AFM). PCL
      homopolymers crystallize directly at the A/W interface in a narrow surface
      pressure range (11-15 mN/m). In the same pressure region, the star-shaped block
      copolymers undergo a phase transition corresponding to the collapse and the
      crystallization of the PCL chains as shown by the presence of a pseudoplateau in
      the isotherms. The LB films were prepared by transferring the Langmuir monolayers
      onto mica substrates at various surface pressures. AFM imaging confirmed the
      formation of PCL crystals in the LB monolayers of the PCL homopolymers and of the
      copolymers, but also showed that the PCL segments can undergo additional
      crystallization after monolayer transfer during water evaporation. The PCL
      crystal morphologies were also strongly influenced by the surface pressure and by
      the PEO segments.

PMID- 17042542
TI  - Chiral recognition of PVBA on Pd(111) and Ag(111) surfaces.
AB  - An asymmetric planar molecule, 4-trans-2-(pyrid-4-yl-vinyl) benzoic acid (PVBA),
      has been used to establish the organic chiral recognition on fcc(111) metal
      surfaces. The strong correlation between the orientation and chiral recognition
      of PVBA on both Ag(111) and Pd(111) guides the choice of a model potential, which
      determines the relative binding energy of PVBA on fcc(111). An angle-dependent
      calculation of relative binding energy reproduces the experimental observation of
      the chiral recognition of PVBA on Ag(111) but not on Pd(111).

PMID- 17042543
TI  - Solid-state NMR and computational chemistry study of mononucleotides adsorbed to
      alumina.
AB  - Solid-state NMR spectroscopy and ab initio computational chemistry are used to
      determine the structure of the complex formed upon adsorption of the
      mononucleotide 2'-deoxyadenosine 5'-monophosphate (dAMP) to the surface of a
      mesoporous alumina. In this multi-technique approach, rotational-echo double
      resonance NMR results reveal that the phosphate group of dAMP interacts
      predominantly with octahedrally coordinated aluminum species at the surface, and
      therefore, adsorption is modeled with both mono- and bidentate sorption of the
      nucleotide phosphate group with octahedral aluminum. 31P chemical shielding
      tensors are calculated from the structure of the lowest energy conformations, and
      these results are compared to tensor values extracted from analysis of spinning
      sideband patterns in the experimental 31P cross-polarization magic-angle-spinning
      NMR spectrum. The chemical shift anisotropy and asymmetry parameter indicate that
      the binding is via a monodentate, inner-sphere complex.

PMID- 17042545
TI  - Surface versus confinement induced morphology transition in triblock copolymer
      films: a grazing incidence small angle neutron scattering investigation.
AB  - The internal nanostructure resulting from microphase separation in triblock
      copolymer films of polyparamethylstyrene-block-polystyrene-block
      polyparamethylstyrene, P(pMS-b-Sd8-b-pMS), has been investigated with grazing
      incidence small angle neutron scattering (GISANS). X-ray reflectivity, grazing
      incidence small-angle X-ray scattering (GISAXS), optical microscopy and atomic
      force microscopy (AFM) complement the investigation. The influence of two
      limiting interfaces present in confinement is compared to the presence of only
      one surface. GISANS allows for the detection of structures in the very limited
      sample volume of confined films as well as for a depth sensitivity to probe the
      near free surface part of bulk films. With respect to the surface a perpendicular
      oriented lamella is observed. In contrast to the shrinkage of the characteristic
      lamellar spacing in confinement at the free surface, a slight increase is
      determined.

PMID- 17042544
TI  - In situ Wilhelmy balance surface energy determination of poly(3-hexylthiophene)
      and poly(3,4-ethylenedioxythiophene) during electrochemical doping-dedoping.
AB  - Changes in the contact angle between conjugated polymers surface poly(3
      hexylthiophene) [P3HT] and poly(3,4-ethylenedioxythiophene) (PEDOT) upon
      electrochemical doping-dedoping in aqueous electrolyte were determined in situ
      using a Wilhelmy plate tensiometer in an electrochemical cell. The hydrophobic
      P3HT was less hydrophobic in the oxidized state than in the neutral state; the
      more hydrophilic PEDOT was less hydrophilic in the oxidized state than when
      neutral. The tensiometry results were in good agreement with those measured by
      contact angle goniometry, and further corroborated by the capillary rise upon
      doping in a fluid cell with two parallel polymer coated plates, another in situ
      dynamic determination method. The contact angle changes depend on doping
      potential, electrolyte type, and concentration. We also deconvoluted the surface
      energy into components of van der Waals and acid-base interactions, using three
      probe liquids on the polymer surfaces, ex situ the electrochemical cell. The
      methods and the obtained results are relevant for the science and technology
      areas of printed electronics and electrochemical devices and for the
      understanding of surface energy modification by electrochemical doping.

PMID- 17042546
TI  - Olefin cross-metathesis of a vinyl-terminated self-assembled monolayer (SAM) on
      Au(111): electrochemical study using a ferrocenyl redox center.
AB  - Self-assembled thiol monolayers bound to single-crystal Au(111) surfaces
      containing a terminal olefin have been prepared and used to monitor
      electrochemically the cross-metathesis (CM) between the surface and an olefin
      terminated ferrocenyl (Fc) derivative from solution over time. Mixed SAM surfaces
      were prepared by first adsorbing a diluent for 2 days followed by the olefinic
      alkanethiol for known adsorption time intervals; three diluents of varying length
      were used. The oxidation peak areas from the voltammetry show the CM reaction
      yields a maximum amount of product at 100-150 min. Beyond this time, thiol
      desorption is apparent and the Fc oxidation peaks diminished. A kinetic
      simulation of the interfacial reactions involving CM and desorption reactions are
      described and aided in the interpretation of the voltammetric responses. The
      length of the diluent and the coverage of surface olefins were important factors
      in limiting undesirable self-CM reactions on the surface, and a model of the
      relationship between the diluent and surface concentration of olefin is
      described. This study shows that attention to monolayer formation and reaction
      conditions are important parameters when maximizing CM yields on surfaces.

PMID- 17042547
TI  - Characterization and surface reactivity of ferrihydrite nanoparticles assembled
      in ferritin.
AB  - Ferrihydrite nanoparticles with nominal sizes of 3 and 6 nm were assembled within
      ferritin, an iron storage protein. The crystallinity and structure of the
      nanoparticles (after removal of the protein shell) were evaluated by high
      resolution transmission electron microscopy (HRTEM), atomic force microscopy
      (AFM), and scanning tunneling microscopy (STM). HRTEM showed that amorphous and
      crystalline nanoparticles were copresent, and the degree of crystallinity
      improved with increasing size of the particles. The dominant phase of the
      crystalline nanoparticles was ferrihydrite. Morphology and electronic structure
      of the nanoparticles were characterized by AFM and STM. Scanning tunneling
      spectroscopy (STS) measurements suggested that the band gap associated with the 6
      nm particles was larger than the band gap associated with the 3 nm particles.
      Interaction of SO2(g) with the nanoparticles was investigated by attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and results were
      interpreted with the aid of molecular orbital/density functional theory (MO/DFT)
      frequency calculations. Reaction of SO2(g) with the nanoparticles resulted
      primarily in SO(3)2- surface species. The concentration of SO3(2-) appeared to be
      dependent on the ferrihydrite particle size (or differences in structural
      properties).

PMID- 17042548
TI  - Green fluorescent protein-expressing Escherichia coli as a model system for
      investigating the antimicrobial activities of silver nanoparticles.
AB  - Recombinant Escherichia coli (E. coli) bacteria expressing green fluorescent
      protein (GFP) was used as a model system to investigate the antimicrobial
      activities of Ag nanoparticles (NPs). A convenient in situ method of Ag NP
      synthesis using sodium borohydride, in the bacterial growth medium, was developed
      to produce preformed NPs for the study. Fluorescence spectroscopic and
      microscopic techniques allowed rapid detection of time-dependent changes in
      bacterial growth as well as fluorescence characteristics in the presence of Ag
      NPs. In addition, X-ray diffraction, UV-vis spectroscopic, and transmission
      electron microscopic measurements were carried out to understand the effect of Ag
      NPs on the bacteria. Our observations indicated that Ag NPs, above a certain
      concentration, not only were bactericidal but also were found to reduce the sizes
      of treated bacteria in comparison to untreated ones. Cell lysis of Ag NP-treated
      bacteria was suggested by the increased GFP fluorescence obtained in the medium.
      In vitro DNA-Ag NP interaction was detected by spectrophotometric analysis.
      However, electrophoresis studies indicated no direct effect of Ag NPs on DNA or
      protein profiles.

PMID- 17042549
TI  - Direct reconstitution of plasma membrane lipids and proteins in nanotube-vesicle
      networks.
AB  - We demonstrate here that nanotube-vesicle networks can be constructed directly
      from plasma membranes of cultured cells. We used a combination of dithiothreitol
      (DTT) and formaldehyde to produce micron-sized plasma membrane vesicles that were
      subsequently shaped into networks using micromanipulation methods previously used
      on purely synthetic systems. Only a single cell is required to derive material
      sufficient to build a small network. This protocol covers the advantages of
      reconstitution in vesicles, such as full control over the solution environment,
      while keeping the proteins in their original surroundings with the proper
      orientation. Furthermore, control of membrane protein and lipid content in the
      networks is achievable by employing different cell types, for example, by
      overexpression of a desired protein or the use of specialized cell-types as
      sources for rare proteins and lipids. In general, the method provides simple
      accessibility for functional studies of plasma membrane constituents.
      Specifically, it provides a direct means to functionalize nanotube-vesicle
      networks with desired proteins and lipids for studies of transport activity both
      across membranes (protein-mediated) and across nanotubes (diffusion), and
      substrate conversion down to the single-molecule limit. Nanotube-vesicle networks
      can adopt different geometries and topologies and undergo shape changes at will,
      providing a flexible system for changing the physical and chemical environment
      around, for example, a membrane protein. Furthermore, the method offers unique
      possibilities for extracting membrane and protein material for nanotechnological
      sensor and analytical devices based on lipid membrane networks.

PMID- 17042550
TI  - Role of the spacer stereochemistry on the aggregation properties of cationic
      gemini surfactants.
AB  - The preparation and characterization of three stereoisomeric cationic gemini
      surfactants, 2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonio)butane
      dibromide, are described. The aggregation properties have been studied by
      fluorescence, electrical conductivity, and quasi-elastic light scattering. A
      conformational study of the surfactant headgroups has been performed by molecular
      mechanics calculations to investigate the effect of the stereogenic centers on
      the surfactant molecular shape and therefore on the different organizations of
      the monomers in the aggregates. Results show that the stereochemistry of the
      spacer strongly influences the aggregation behavior of the diasteromeric gemini
      in water.

PMID- 17042551
TI  - Surface sticking and lateral diffusion of lipids in supported bilayers.
AB  - The diffusion of fluorescently labeled lipids in supported bilayers is studied
      using two different methods: Z-scan fluorescence correlation spectroscopy (z-scan
      FCS) and two-focus fluorescence correlation spectroscopy (2f-FCS). It is found
      that the data can be fitted consistently only when taking into account partial
      sticking of the labeled lipids to the supporting glass surface. A kinetic
      reaction-diffusion model is developed and applied to the data. We find a very
      slow sticking rate which, however, when neglected, leads to strongly varying
      estimates of the free diffusion coefficient. The study reveals a strong
      sensitivity of FCS on even slight binding/unbinding kinetics of the labeled
      molecules, which has significance for related diffusion measurements in cellular
      lipid membranes.

PMID- 17042552
TI  - Fabrication of glycosylated surface on polymer membrane by UV-induced graft
      polymerization for lectin recognition.
AB  - Increasingly, carbohydrate-protein interactions are viewed as important
      mechanisms for many biological processes such as blood coagulation, immune
      response, viral infection, inflammation, embryogenesis, and cellular signal
      transfer. However, the weak affinity of the interactions and the structural
      complexity of carbohydrates have hindered efforts to develop a comprehensive
      understanding of carbohydrate functions. Fortunately, synthetic polyvalent
      glycoligands give us a chance to reveal the nature of these biological processes.
      In this work a sugar-containing monomer (alpha-D-allyl glucoside (AG)) was
      grafted onto polypropylene microporous membrane (PPMM) by UV-induced graft
      polymerization to generate a glycosylated porous surface for the first time.
      Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and
      scanning electron microscopy were employed to confirm the glycosylation. Water
      contact angle measurement was used to evaluate the hydrophilicity change of the
      surfaces before and after the graft polymerization of AG. It was found that the
      grafting density increased reasonably with the increase of AG monomer
      concentration, and then this increase slowed when the AG concentration exceeded
      80 g/L. At the same time a 20-25 min UV irradiation was enough for the grafting
      polymerization. The photoinitiator concentration also influenced the grafting
      density obviously, and there was an optimal concentration of the photoinitiator
      for the grafting process. The water contact angle of the polyAG-tethered membrane
      surface decreased from 149 degrees to 80 degrees with the increase of grafting
      density from 0 to 187.76 microg/cm2, which indicated a hydrophilic variation of
      the membrane surface by the grafting of AG. Results also indicated that the
      surface-grafted polyAG chains showed weak interaction with Con A when the
      grafting density was low. However, when the sugar density exceeded 90 microg/cm2,
      the binding affinity increased dramatically which was the due to the "glycoside
      cluster effect".

PMID- 17042553
TI  - Phenylalanine and arginine adsorption in zeolites X, Y, and Beta.
AB  - This paper documents a continuation of work published in Langmuir 2005, 21, 8743
      8750. We report new aspects of this amino acid adsorption study, including the
      effect of changing zeolite framework type and results from adsorption of mixed
      amino acids. In single-amino-acid adsorption experiments, zeolite Y (Si/Al=2.5)
      was found to adsorb no phenylalanine while admitting arginine to a similar extent
      as observed with zeolite beta. Using this zeolite Y, we measured mixed-amino-acid
      separation selectivities for arginine/phenylalanine as large as 25,000 or 2
      orders of magnitude larger than the corresponding selectivities measured with
      zeolite beta.

PMID- 17042554
TI  - A test of the transition-metal nanocluster formation and stabilization ability of
      the most common polymeric stabilizer, poly(vinylpyrrolidone), as well as four
      other polymeric protectants.
AB  - Following an introduction to the nanocluster stabilization literature and DLVO
      (Derjaugin-Landau-Verwey-Overbeek) theory of colloidal stability, the most common
      steric stabilizer of transition-metal nanoclusters, poly(vinylpyrrolidone) (PVP),
      has been examined for its efficacy in the formation, stabilization, and
      subsequent catalytic activity of prototype, test case Ir(0)n nanoclusters. First,
      the five criteria established previously for ranking nanocluster protectants for
      their nanocluster formation and stabilization ability were evaluated for 1
      monomer equiv of 10000 average molecular weight (MWav) PVP in the absence, and
      then presence, of the traditionally weakly coordinating anion BF4- as well as the
      absence and presence of the strongly coordinating, superior anionic stabilizer
      P2W15Nb3O62(9-), all in propylene carbonate solvent. It is found that neither 1
      equiv of BF4- in propylene carbonate nor 1 monomer equiv of (undried) PVP alone
      allows for isolable and redissolvable nanoclusters without bulk Ir(0)n metal
      formation. Careful predrying of the PVP, and by implication other polymers, is
      shown to be necessary for the formation and stabilization of the nanoclusters.
      Next, 40 monomer equiv of 10000 MWav PVP and 1 equiv of BF4- in propylene
      carbonate are shown to allow isolable, redissolvable nanoclusters. Control
      experiments reveal little difference on nanocluster stabilization by 3500 or
      55000 (i.e., vs 10,000) MWav PVP, but yield interesting effects on nanocluster
      nucleation by the 3500 MWav PVP, as well as by the polymer
      poly(bis(ethoxy)phosphazene) (PBEP). Four other key polymers reported in the
      literature to be nanocluster stabilizers are tested by the five criteria method
      for their efficacy in the formation and stabilization of Ir0n nanoclusters (now
      in acetone due to the polymers' solubility) and in comparison to each other,
      specifically, poly(methyl methacrylate) (PMMA), poly(styrene) (PS),
      poly(methylhydrosilane) (PMHS), and PBEP. Only 40 monomer equiv dried PMMA allows
      isolable and redissolvable nanoclusters in acetone. Control/reference point
      experiments show that the electrostatic stabilizer P2W15Nb3O62(9-) is superior to
      each of the five polymeric stabilizers studied herein in both acetone and
      propylene carbonate, at least for the test case of Ir(0)n nanoclusters. Further
      controls show that 40 monomer equiv of PVP added to P2W15Nb3O(62)9--stabilized
      nanoclusters has no discernible effect on the five criteria other than to reduce
      by approximately 50% the nanocluster catalytic activity and total catalytic
      lifetime for cyclohexene hydrogenation. The main finding of this work is that
      DLVO theory as applied to nanocluster stabilization is fully supported; that is,
      surface-bound anions in high dielectric constant solvents provide superior
      stabilization. The importance of even traditionally weakly coordinating anions
      such as BF4- in nanocluster stabilization is a second, important finding of this
      work. The fact that HPO4(2-) has been shown to be a simple, cheap, commercially
      available, thermally robust, and 31P-NMR-handle-containing analogue of the more
      esoteric P2W15Nb3O62(9-) stabilizer is also discussed in the 14 total Conclusions
      from this first study ranking polymeric stabilizers of modern transition-metal
      nanoclusters.

PMID- 17042555
TI  - Nanoporous structured submicrometer carbon fibers prepared via solution
      electrospinning of polymer blends.
AB  - A facile means for obtaining submicrometer carbon fibers with a nanoporous
      structure is presented. A mixture of polyacrylonitrile (PAN) and a copolymer of
      acrylonitrile and methyl methacrylate (poly(AN-co-MMA)) in dimethylformamide was
      electrospun into submicrometer fibers with a microphase-separated structure.
      During the followed oxidation process, the copolymer domains were pyrolyzed,
      resulting in a nanoporous structure that was preserved after carbonization. The
      microphase-separated structure of the PAN/poly(AN-co-MMA) electrospun fibers, the
      morphology, and porous structure of both the oxidized and the carbonized fibers
      were observed with scanning electron microscopy and transmission electron
      microscopy. The carbon fibers have diameters ranging from several hundred
      nanometers to about 1 microm. The nanopores or nanoslits throughout the fiber
      surface and interior with diameters of several tens of nanometers are
      interconnected and oriented along the longitudinal axis of the fibers. This
      unique nanoporous morphology similar to the microphase-separated structure in the
      PAN/poly(AN-co-MMA) fibers is attributed to the rapid phase separation,
      solidification, as well as the stretching of the fibers during electrospinning.
      The pore volume and pore size distribution of the carbonized fibers were
      investigated by nitrogen adsorption and desorption.

PMID- 17042556
TI  - Swelling behavior of chitosan hydrogels in ionic liquid-water binary systems.
AB  - The swelling behavior of chitosan hydrogels in ionic liquid-water binary systems
      was studied using hydrophilic room-temperature ionic liquids (RTILs) to elucidate
      the swelling mechanism of chitosan hydrogels. No penetration of RTIL into a dry
      chitosan material was observed. Swelling was achieved by soaking in water-RTIL
      binary mixtures, with larger swelling observed at higher water contents. In one
      instance, the binary mixture was acidic and produced larger than expected
      swelling due to the dissociation of the amine groups in the chitosan. The
      equilibrium binary system content behavior of the chitosan hydrogels depended
      upon the amount of free water, which is a measure of the number of water
      molecules that do not interact with the ionic liquid. After evaporation of water,
      remnant RTIL remained in the chitosan network and hardness testing indicated a
      plasticization effect, suggesting that the RTIL molecularly mixed with the
      chitosan. Chitosan hydrogels containing only RTIL were prepared by dropping pure
      RTIL onto a fully preswollen hydrogel followed by water evaporation. This method
      may be a useful means for preparing air-stable swollen chitosan gels.

PMID- 17042557
TI  - In2O3 hollow microspheres: synthesis from designed In(OH)3 precursors and
      applications in gas sensors and photocatalysis.
AB  - In this work, well-shaped In(OH)3 hollow microspheres have been successfully
      prepared via a novel surfactant-free vesicle-template-interface route in the
      "formamide-resorcinol-water" system, in which spontaneous vesicles were formed
      under hydrothermal conditions and NH3 from the hydrolysis of formamide acted as
      the OH- provider. Morphological and structural characterizations indicate that
      the shells of as-prepared In(OH)3 hollow microspheres were constructed by
      numerous nanocubes about 80 nm in size. As desired, In2O3 hollow microspheres
      were obtained from annealing the designed In(OH)3 precursors, and the as-obtained
      In2O3 hollow microspheres performed well as a gas-sensing material in response to
      both ethanol and formaldehyde gases and as a photocatalyst for photocatalytic
      degradation of rhodamine B. The facile preparation method and the improved
      properties derived from special microstructures are significant in the synthesis
      and future applications of functional nanomaterials.

PMID- 17042558
TI  - Ionic liquids in vacuo: analysis of liquid surfaces using ultra-high-vacuum
      techniques.
AB  - Ultra-high-vacuum (UHV)-based techniques can offer the scientist a tremendous
      amount of information about samples of interest. However, until recently the
      range of samples that could be routinely investigated using unmodified
      instrumentation was limited to solid samples and frozen solutions. In this paper
      we report the investigation of low-vapor-pressure, liquid samples using both X
      ray photoelectron spectroscopy and time-of-flight secondary ion mass
      spectrometry. We demonstrate the suitability of UHV techniques in the
      investigation of a range of room-temperature ionic liquids, offering the
      opportunity to measure high-quality solution-phase spectra using unmodified
      instrumentation.

PMID- 17042559
TI  - Formation of gold@polymer core-shell particles and gold particle clusters on a
      template of thermoresponsive and pH-responsive coordination triblock copolymer.
AB  - Template synthesis of various morphological gold colloidal nanoparticles using a
      thermoresponsive and pH-responsive coordination triblock copolymer of
      poly(ethylene glycol)-b-poly(4-vinylpyridine)-b-poly(N-isopropylacrylamide) is
      studied. The template morphology of the thermoresponsive and pH-responsive
      coordination triblock copolymer, which can be tuned by simply changing the pH or
      temperature of the triblock copolymer aqueous solution, ranges from single chains
      to core-corona micelles and further to micellar clusters. Various morphological
      gold colloidal nanoparticles such as discrete gold nanoparticles, gold@polymer
      core-shell nanoparticles, and gold nanoparticle clusters are synthesized on the
      corresponding template of the triblock copolymer by first coordination with gold
      ions and then reduction by NaBH4. All three resultant gold colloidal
      nanoparticles are stable in aqueous solution, and their sizes are 2, 10, and 7
      nm, respectively. The gold@polymer core-shell nanoparticles are thermoresponsive.
      The gold nanoparticle cluster has a novel structure, and each one holds about 40
      single gold nanoparticles.

PMID- 17042560
TI  - Effect of colloidal stabilizer on the shape of polystyrene/poly(methyl
      methacrylate) composite particles prepared in aqueous medium by the solvent
      evaporation method.
AB  - Effects of the kind and concentration of stabilizers on the nonspherical shape of
      polystyrene (PS)/poly(methyl methacrylate) (PMMA) composite particles prepared by
      release of toluene from PS/PMMA/toluene droplets dispersed in stabilizer aqueous
      solution were examined. In the case of poly(vinyl alcohol), the surfaces of the
      obtained particles always had a single dimple. In the case of sodium dodecyl
      sulfate (SDS), the shapes of the composite particles changed from the dimple, via
      acorn, to spherical with increasing SDS concentration. It was clarified that the
      dimple and acorn shapes of the PS/PMMA composite particles were caused by
      contraction of the PS phase after hardening of the PMMA phase in excentered core
      shell and hemisphere morphologies, respectively, which were formed by phase
      separation during toluene evaporation.

PMID- 17042561
TI  - Pretilt angle of liquid crystals and liquid-crystal alignment on microgrooved
      polyimide surfaces fabricated by soft embossing method.
AB  - In this study, the soft embossing method is proposed to fabricate periodical
      microgrooved structure on polyimide surfaces. These microgrooved polyimide
      surfaces are assembled to form liquid-crystal cells. It is found that the
      director of liquid crystals uniformly aligns along the groove direction even when
      the groove width is as high as 3 microm. The anchoring energy of these
      microgrooved polyimide surfaces is higher than that of the typical rubbed
      surfaces. The pretilt angle of liquid crystals is adjusted by tuning the surface
      polarity of the polyimide alignment layer, which is identified by the advancing
      contact angle of water. The surface polarity of polyimide alignment layers is
      manipulated by simply mixing two kinds of polyimide: a more hydrophilic one and a
      more hydrophobic one. It is found that the pretilt angle of liquid crystals
      increases along with the advancing contact angle of water on the alignment layer
      under the condition of a fixed surface topography.

PMID- 17042562
TI  - Morphologies of multicompartment micelles formed by ABC miktoarm star
      terpolymers.
AB  - Several new multicompartment micellar structures have been identified by
      cryogenic transmission electron microscopy (cryoTEM) from the aqueous self
      assembly of mu-[poly(ethylethylene)][poly(ethylene
      oxide)][poly(perfluoropropylene oxide)] (mu-EOF) miktoarm star terpolymers. This
      work extends our previous studies, in which it was found that, upon decreasing
      the length of the hydrophilic block (O), the resulting micelles evolved from
      "hamburger" micelles to segmented worms and ultimately to nanostructured bilayers
      and vesicles. In the terpolymers examined here segmented ribbons and bilayers
      were found at an intermediate composition between segmented worms and
      nanostructured bilayers, provided that the fluoropolymer (F) was the minority
      component in the micelle core. On the other hand, when the F block exceeded the
      chain length of the hydrocarbon block (E), the superhydrophobic F block imposed a
      "double frustration" on the self-assembly of the mu-EOF(2-9-5) terpolymer; while
      F prefers to minimize its interfacial contact with the O corona, it must occupy
      the majority of the micellar core. Therefore, a richer variety of
      multicompartment micelles, including well-defined segmented worms, raspberry-like
      micelles, and multicompartmentalized worms, were formed from one terpolymer, as
      revealed by cryoTEM. Despite the complexity and variety of the observed aggregate
      morphologies, a small number of common structural elements can be invoked to
      interpret the observed micelles and to relate a given structure to the terpolymer
      composition.

PMID- 17042564
TI  - Role of the critical micelle concentration in the electrochemical deposition of
      nanostructured ZnO films under utilization of amphiphilic molecules.
AB  - A detailed understanding of micelle formation that occurs above a critical
      micelle concentration (cmc) is a crucial point for the surfactant-assisted
      preparation of porous materials such as molecular sieves. However, the role of
      the cmc in the surfactant-assisted electrodeposition of porous oxides is widely
      unknown. In this study, we investigated the electrodeposition of ZnO films under
      utilization of alkyl sulfates and alkyl sulfonates with different chain lengths.
      Cmc values of the surfactants were measured directly in the electrodeposition
      bath by surface tension measurements. Subsequently, we performed
      electrodeposition with surfactant concentrations from above the cmc down to
      concentrations well below the cmc. Beside a lamellar ZnO phase already known from
      earlier studies, a second nanoparticular ZnO phase was found at concentrations
      below the cmc.

PMID- 17042563
TI  - Electrostatic stretching of a charged vesicle.
AB  - We present a closed-form solution of electrostatic potential self-induced by a
      uniformly charged micro/nanovesicle and the corresponding elastic deformation of
      the vesicle membrane due to Maxwell stress. At equilibrium, the electrostatic
      force induced on both sides of the membrane is balanced by the elastic force of
      the stretched membrane. We develop differential and integral solutions of the
      coupled Poisson-Boltzmann system for a spherical vesicle and demonstrate that the
      integral solution is relatively flexible in formulating asymmetric
      configurations. Analytical results are formulated in terms of vesicle size, Debye
      length, and the surface charge density. The membrane stretching is characterized
      by the dimensionless group that defines the relative strength of the net electric
      force with respect to the membrane stiffness. We found that the self-induced
      electrostatic interaction will lead to a pre-stressed membrane although the small
      displacement is often negligible compared with the vesicle size. Quantitative
      analysis also reveals that the electric force can assist the vesicle in
      recovering its opening pore.

PMID- 17042565
TI  - Formation of a perylenetetracarboxylic diimide network film by post
      electrochemical treatment.
AB  - Perylenetetracarboxylic diimide (PDI) derivatives bearing two or four peripheral
      pyrrole pendants (PDI-nPy, n=2 or 4) are cross-linkable materials by
      electro/phototreatment. In this paper, we introduce a new posttreatment technique
      to produce an insoluble film. Unlike the common solution-phase electrochemical
      deposition, we first spin-coated PDI-nPy on an electrode and then electrotreated
      the coated surface in a monomer-free electrolyte solution. This method gives the
      film a smooth surface with no granules, while the common method induces a rough
      film with a lot of granules. The post electrochemical treatment also provides a
      merit of higher resolution in a patterning process on a specific metal electrode.
      As one of the applications, we carried out an electrochromic study on the
      posttreated PDI-4Py film. It turned purple (lambdamax=590 nm) and sky blue
      (lambdamax=797 nm) at 0 and -1.9 V vs Ag/Ag+, respectively. We believe this
      method will broaden the patterning concept with the desired film morphology and
      resolution using PDI on a specific electrode.

PMID- 17042566
TI  - Photolabile carboxylic acid protected terpolymers for surface patterning. Part 1:
      Polymer synthesis and film characterization.
AB  - We present the synthesis and characterization of a series of photolabile phenacyl
      derivative polymers and their subsequent thin film preparation. These systems are
      composed of up to three methacrylate units: a photolabile component including a p
      methoxyphenacyl moiety which after selective irradiation (UV/laser) can provide
      free carboxylic groups in specific areas for further modification; an anchoring
      unit, trimethoxysiloxane or glycidyl methacrylate derivative, which allows the
      covalent attachment of the polymer to the substrate; and a spacer, methyl
      methacrylate or styrene, which in the appropriate proportion ensures the
      formation of films with good quality. Structural and thermal properties of these
      materials have been analyzed by means of NMR, FTIR, elemental analysis, UV, gel
      permeation chromatography, differental scanning calorimetry, and
      thermogravimetric analysis. The polymers have been subsequently processed by spin
      coating to render ultrathin films (<50 nm). Topographic and structural
      characterization studies of the films have been carried out with atomic force
      microscopy, contact angle measurements, and X-ray photoelectron spectroscopy. The
      extent of the substrate attachment of the polymers depending on the nature of the
      anchoring groups have been studied by ellipsometry and FTIR.

PMID- 17042567
TI  - Photolabile carboxylic acid protected terpolymers for surface patterning. Part 2:
      Photocleavage and film patterning.
AB  - The surface properties of films made of p-methoxyphenacyl derivative terpolymers,
      associated with photocleavage by UV irradiation, and their optical patterning are
      investigated. The deprotection reaction has been monitored by UV and FTIR
      spectroscopy, contact angle measurements, and X-ray photoelectron spectroscopy,
      revealing the photoremoval of the protecting p-methoxyphenacyl group in high
      yields under mild conditions. Parallel and serial patterning of the films has
      been performed by selective irradiation through optical masks and by laser
      irradiation via fiber tips of a scanning near-field optical microscope,
      respectively. By irradiation of photolabile protected functional groups, free
      carboxylic groups become exposed to the surface with which fluorescent dyes and
      proteins can be associated specifically.

PMID- 17042568
TI  - Shape-controlled production of biodegradable calcium alginate gel microparticles
      using a novel microfluidic device.
AB  - In this paper we describe a novel method of manufacturing shape-controlled
      calcium alginate gel microparticles in a microfluidic device. Both manufacturing
      shape-controlled microparticles and synthesizing hydrogel microparticles could be
      performed simultaneously in the microfluidic device. The novel microfluidic
      device comprised of two individual flow-focusing channels and a synthesizing
      channel was successfully applied as a continuous microfluidic reactor to
      synthesize gel microparticles with size and shape control. By passive control
      based on the microchannel geometric confinement and liquid-phase flow rates, we
      succeeded in producing monodisperse sodium alginate microparticles with diverse
      shapes (such as plugs, disks, microspheres, rods, and threads) in the flow
      focusing channels of the microfluidic device. The shape and size of the sodium
      alginate microparticles could be tuned by adjusting the flow rates of the various
      streams. Further stages of the chemical reaction could be initiated by mixing
      sodium alginate microparticles and calcium chloride (CaCl2) solution in the
      synthesizing channel. The shapes of the sodium alginate microparticles could be
      permanently preserved by the synthesis of calcium alginate gel microparticles.
      The preparation conditions of size- and shape-controlled calcium alginate
      microparticles and influence factors were studied.

PMID- 17042569
TI  - Surface modification for enhancing antibody binding on polymer-based microfluidic
      device for enzyme-linked immunosorbent assay.
AB  - A novel surface treatment method using poly(ethyleneimine) (PEI), an amine
      bearing polymer, was developed to enhance antibody binding on the poly(methyl
      methacrylate) (PMMA) microfluidic immunoassay device. By treating the PMMA
      surface of the microchannel on the microfluidic device with PEI, 10 times more
      active antibodies can be bound to the microchannel surface as compared to those
      without treatment or treated with the small amine-bearing molecule,
      hexamethylenediamine (HMD). Consequently, PEI surface modification greatly
      improved the immunoassay performance of the microfluidic device, making it more
      sensitive and reliable in the detection of IgG. The improvement can be attributed
      to the spacer effect as well as the functional amine groups provided by the
      polymeric PEI molecules. Due to the smaller dimensions (140x125 microm) of the
      microchannel, the time required for antibody diffusion and adsorption onto the
      microchannel surface was reduced to only several minutes, which was 10 times
      faster than the similar process carried out in 96-well plates. The microchip also
      had a wider detection dynamic range, from 5 to 1000 ng/mL, as compared to that of
      the microtiter plate (from 2 to 100 ng/mL). With the PEI surface modification,
      PMMA-based microchips can be effectively used for enzyme linked immunosorbent
      assays (ELISA) with a similar detection limit, but much less reagent consumption
      and shorter assay time as compared to the conventional 96-well plate.

PMID- 17042570
TI  - Intramolecular vibrational energy redistribution as state space diffusion:
      classical-quantum correspondence.
AB  - We study the intramolecular vibrational energy redistribution (IVR) dynamics of
      an effective spectroscopic Hamiltonian describing the four coupled high frequency
      modes of CDBrClF. The IVR dynamics ensuing from nearly isoenergetic zeroth-order
      states, an edge (overtone) and an interior (combination) state, is studied from a
      state space diffusion perspective. A wavelet based time-frequency analysis
      reveals an inhomogeneous phase space due to the trapping of classical
      trajectories. Consequently the interior state has a smaller effective IVR
      dimension as compared to the edge state.

PMID- 17042571
TI  - A quantitative account of quantum effects in liquid water.
AB  - We report converged quantum statistical mechanical simulations of liquid water
      with the Thole-type Model (version 2.1), Flexible, polarizable (TTM2.1-F)
      interaction potential for water. Simulations of total length of 600 ps with a
      0.05 fs time step for a periodic unit cell of 256 molecules with up to 32
      replicas per atom suggest that the quantum effects contribute 1.01+/-0.02
      kcal/mol to the liquid enthalpy of formation at 298.15 K. They furthermore
      demonstrate for the first time a quantitative agreement with experiment for the
      heights and broadening of the intramolecular OH and HH peaks in the radial
      distribution functions.

PMID- 17042572
TI  - Photo ejection of water molecules from amorphous ice films.
AB  - Water molecules are photo-ejected upon laser irradiation from the surface of ice
      films grown on graphite (0001) and Pt(111). The films are deposited at
      temperatures between 40 and 140 K and irradiated with nanosecond laser pulses.
      The process is investigated in the wavelength range between 275 and 670 nm. The
      wavelength and photon flux dependence suggest a multi-photon process with energy
      threshold of around 9 eV. The photo-detachment is less effective or negligible
      from films annealed at temperatures above the amorphous-crystalline transition
      temperature of ice films. Coverage dependence of the phenomena relates the photo
      yield to surface roughness. Electronic excitation mechanism related to the
      defects in ice is proposed to explain the observations.

PMID- 17042573
TI  - Multireference correlation in long molecules with the quadratic scaling density
      matrix renormalization group.
AB  - We have devised a local ab initio density matrix renormalization group algorithm
      to describe multireference correlations in large systems. For long molecules that
      are extended in one of their spatial dimensions, we can obtain an exact
      characterization of correlation, in the given basis, with a cost that scales only
      quadratically with the size of the system. The reduced scaling is achieved solely
      through integral screening and without the construction of correlation domains.
      We demonstrate the scaling, convergence, and robustness of the algorithm in
      polyenes and hydrogen chains. We converge to exact correlation energies (in the
      sense of full configuration interaction, with 1-10 microE(h) precision) in all
      cases and correlate up to 100 electrons in 100 active orbitals. We further use
      our algorithm to obtain exact energies for the metal-insulator transition in
      hydrogen chains and compare and contrast our results with those from conventional
      quantum chemical methods.

PMID- 17042574
TI  - Computation of dipole, quadrupole, and octupole surfaces from the variational two
      electron reduced density matrix method.
AB  - Recent advances in the direct determination of the two-electron reduced density
      matrix (2-RDM) by imposing known N-representability conditions have mostly
      focused on the accuracy of molecular potential energy surfaces where
      multireference effects are significant. While the norm of the 2-RDM's deviation
      from full configuration interaction has been computed, few properties have been
      carefully investigated as a function of molecular geometry. Here the dipole,
      quadrupole, and octupole moments are computed for a range of molecular
      geometries. The addition of Erdahl's T2 condition [Int. J. Quantum Chem. 13, 697
      (1978)] to the D, Q, and G conditions produces dipole and multipole moments that
      agree with full configuration interaction in a double-zeta basis set at all
      internuclear distances.

PMID- 17042575
TI  - Electron-electron and electron-nucleus correlation effects on exponent values of
      Gaussian-type functions for quantum protons and deuterons.
AB  - Electron-electron and electron-nucleus correlation effects on exponent (alpha)
      values of Gaussian-type functions (GTFs) for quantum protons and deuterons in
      BH3, CH4, NH3, H2O, and HF molecular systems and their deuterated counterparts
      were analyzed using the second-order Moller-Plesset (MP2) level of theory of the
      multicomponent molecular orbital (MCMO-MP2) method. This method can
      simultaneously determine both nuclear and electronic wave functions. Results
      showed that the average alpha value (alpha(ave)) of the optimized alpha in single
      s-type ([1s]) GTF for a proton and a deuteron is similar to that determined using
      the Hartree-Fock level of the MCMO (MCMO-HF) method. In contrast, due to the
      electron-nucleus correlation effect, the s- and p-type ([1s1p]) GTFs are
      delocalized compared with those determined using the MCMO-HF method. For the H
      bonded complexes, differences in the interaction energy induced by the H/D
      isotope effect were clearly evident because the D...Y bond distance for D complex
      is longer than the H...Y for H complex. Also, the basis set superposition error
      for the interaction energy in every H complex was similar to that in every D
      complex. The results here clearly demonstrate that the protonic and deuteronic
      basis functions based on alpha(ave) values for correlation effects can be applied
      to the detailed analysis of the quantum effects of protons and the H/D isotope
      effect in widespread fields that involve H bonds and weak interactions, such as
      the function of biological molecules, chemical reaction processes, and the design
      of new materials.

PMID- 17042576
TI  - Condensed phase ionic polarizabilities from plane wave density functional theory
      calculations.
AB  - A method is presented to allow the calculation of the dipole polarizabilities of
      ions and molecules in a condensed-phase coordination environment. These values
      will be useful for understanding the optical properties of materials and for
      developing simulation potentials which incorporate polarization effects. The
      reported values are derived from plane wave density functional theory
      calculations, though the method itself will apply to first-principles
      calculations on periodic systems more generally. After reporting results of test
      calculations on atoms to validate the procedure, values for the polarizabilities
      of the oxide ion and various cations in a range of materials are reported and
      compared with experimental information as well as previous theoretical results.

PMID- 17042577
TI  - Cumulative reaction probabilities: A comparison between quasiclassical and
      quantum mechanical results.
AB  - This article presents a quasiclassical trajectory (QCT) method for determining
      the cumulative reaction probability (CRP) as a function of the total energy. The
      method proposed is based on a discrete sampling using integer values of the total
      and orbital angular momentum quantum numbers for each trajectory and on the
      development of equations that have a clear counterpart in the quantum mechanical
      (QM) case. The calculations comprise cumulative reaction probabilities at a given
      total angular momentum J, as well as those summed over J. The latter are used to
      compute QCT rate constants. The method is illustrated by comparing QCT and exact
      QM results for the H+H2, H+D2, D+H2, and H+HD reactions. The agreement between
      QCT and QM results is very good, with small discrepancies between the two data
      sets indicating some genuine quantum effects. The most important of these
      involves the value of the CRP at low energies which, due to the absence of
      tunneling, is lower in the QCT calculations, causing the corresponding rate
      constants to be smaller. The second is the steplike structure that is clearly
      displayed in the QM CRP for J = 0, which is much smoother in the corresponding
      QCT results. However, when the QCT density of reactive states, i.e., the
      derivatives of the QCT CRP with respect to the energy, is calculated, a
      succession of maxima and minima is obtained which roughly resembles those found
      in the QM calculations, although the latter are considerably sharper. The
      analysis of the broad peaks in the QCT density of reactive states indicates that
      the distributions of collision times associated with the maxima are somewhat
      broader, with a tail extending to larger collision times, than those associated
      with the minima. In addition, the QM and QCT dynamics of the isotopic variants
      mentioned above are compared in the light of their CRPs. Issues such as the
      compliance of the QCT CRP with the law of microscopic reversibility, as well as
      the similarity between the CRPs for ortho and para species in the QM and QCT
      cases, are also addressed.

PMID- 17042578
TI  - Extracting effective normal modes from equilibrium dynamics at finite
      temperature.
AB  - A general method for obtaining effective normal modes of a molecular system from
      molecular dynamics simulations is presented. The method is based on a
      localization criterion for the Fourier transformed velocity time-correlation
      functions of the effective modes. For a given choice of the localization function
      used, the method becomes equivalent to the principal mode analysis (PMA) based on
      covariance matrix diagonalization. On the other hand, a proper choice of the
      localization function leads to a novel method with a strong analogy with the
      usual normal mode analysis of equilibrium structures, where the Hessian system at
      the minimum energy structure is replaced by the thermal averaged Hessian,
      although the Hessian itself is never actually calculated. This method does not
      introduce any extra numerical cost during the simulation and bears the same
      simplicity as PMA itself. It can thus be readily applied to ab initio molecular
      dynamics simulations. Three such examples are provided here. First we recover
      effective normal modes of an isolated formaldehyde molecule computed at 20 K in
      very good agreement with the results of a normal mode analysis performed at its
      equilibrium structure. We then illustrate the applicability of the method for
      liquid phase studies. The effective normal modes of a water molecule in liquid
      water and of a uracil molecule in aqueous solution can be extracted from ab
      initio molecular dynamics simulations of these two systems at 300 K.

PMID- 17042579
TI  - A "partitioned leaping" approach for multiscale modeling of chemical reaction
      dynamics.
AB  - We present a novel multiscale simulation approach for modeling stochasticity in
      chemical reaction networks. The approach seamlessly integrates exact-stochastic
      and "leaping" methodologies into a single partitioned leaping algorithmic
      framework. The technique correctly accounts for stochastic noise at significantly
      reduced computational cost, requires the definition of only three model
      independent parameters, and is particularly well suited for simulating systems
      containing widely disparate species populations. We present the theoretical
      foundations of partitioned leaping, discuss various options for its practical
      implementation, and demonstrate the utility of the method via illustrative
      examples.

PMID- 17042580
TI  - W4 theory for computational thermochemistry: In pursuit of confident sub-kJ/mol
      predictions.
AB  - In an attempt to improve on our earlier W3 theory [A. D. Boese et al., J. Chem.
      Phys. 120, 4129 (2004)] we consider such refinements as more accurate estimates
      for the contribution of connected quadruple excitations (T4), inclusion of
      connected quintuple excitations (T5), diagonal Born-Oppenheimer corrections
      (DBOC), and improved basis set extrapolation procedures. Revised experimental
      data for validation purposes were obtained from the latest version of the Active
      Thermochemical Tables thermochemical network. The recent CCSDT(Q) method offers a
      cost-effective way of estimating T4, but is insufficient by itself if the
      molecule exhibits some nondynamical correlation. The latter considerably slows
      down basis set convergence for T4, and anomalous basis set convergence in highly
      polar systems makes two-point extrapolation procedures unusable. However, we
      found that the CCSDTQ-CCSDT(Q) difference converges quite rapidly with the basis
      set, and that the formula 1.10[CCSDT(Q)cc-pVTZ+CCSDTQcc-pVDZ-CCSDT(Q)cc-pVDZ]
      offers a very reliable as well as fairly cost-effective estimate of the basis set
      limit T4 contribution. The T5 contribution converges very rapidly with the basis
      set, and even a simple double-zeta basis set appears to be adequate. The largest
      T5 contribution found in the present work is on the order of 0.5 kcal/mol (for
      ozone). DBOCs are significant at the 0.1 kcal/mol level in hydride systems. Post
      CCSD(T) contributions to the core-valence correlation energy are only significant
      at that level in systems with severe nondynamical correlation effects. Based on
      the accumulated experience, a new computational thermochemistry protocol for
      first- and second-row main-group systems, to be known as W4 theory, is proposed.
      Its computational cost is not insurmountably higher than that of the earlier W3
      theory, while performance is markedly superior. Our W4 atomization energies for a
      number of key species are in excellent agreement (better than 0.1 kcal/mol on
      average, 95% confidence intervals narrower than 1 kJ/mol) with the latest
      experimental data obtained from Active Thermochemical Tables. Lower-cost variants
      are proposed: the sequence W1-->W2.2-->W3.2-->W4lite-->W4 is proposed as a
      converging hierarchy of computational thermochemistry methods. A simple a priori
      estimate for the importance of post-CCSD(T) correlation contributions (and hence
      a pessimistic estimate for the error in a W2-type calculation) is proposed.

PMID- 17042581
TI  - The Jarzynski identity derived from general Hamiltonian or non-Hamiltonian
      dynamics reproducing NVT or NPT ensembles.
AB  - The Jarzynski identity (JI) relates nonequilibrium work averages to thermodynamic
      free energy differences. It was shown in a recent contribution [M. A. Cuendet,
      Phys. Rev. Lett. 96, 120602 (2006)] that the JI can, in particular, be derived
      directly from the Nose-Hoover thermostated dynamics. This statistical mechanical
      derivation is particularly relevant in the framework of molecular dynamics
      simulation, because it is based solely on the equations of motion considered and
      is free of any additional assumptions on system size or bath coupling. Here, this
      result is generalized to a variety of dynamics, along two directions. On the one
      hand, specific improved thermostating schemes used in practical applications are
      treated. These include Nose-Hoover chains, higher moment thermostats, as well as
      an isothermal-isobaric scheme yielding the JI in the NPT ensemble. On the other
      hand, the theoretical generality of the new derivation is explored. Generic
      dynamics with arbitrary coupling terms and an arbitrary number of thermostating
      variables, both non-Hamiltonian and Hamiltonian, are shown to imply the JI. In
      particular, a nonautonomous formulation of the generalized Nose-Poincare
      thermostat is proposed. Finally, general conditions required for the JI
      derivation are briefly discussed.

PMID- 17042582
TI  - Effective multipoles and Yukawa electrostatics in dressed molecule theory.
AB  - In this paper we derive the multipolar expansion of the screened Coulomb
      potential in electrolyte solutions with molecular solvent. The solute and solvent
      molecules can have arbitrary sizes, shapes, and internal charge distributions. We
      use the exact statistical mechanical definition of renormalized charge
      distributions coming from "dressed molecule theory" to determine the effective
      multipoles of a molecule immersed in an electrolyte. The effects of many-body
      correlations are fully included in our formally exact theory. We restrict
      ourselves to sufficiently dilute solutions so the screened Coulomb potential
      decays for large distances like a Yukawa function, exp(-kappa r)/r, where r is
      the distance and 1/kappa is the decay length (it is normally different from the
      Debye length). The resulting "Yukawa electrostatics" differ in many respects from
      ordinary, unscreened electrostatics. The "Yukawa charge" of a molecule (the
      lowest order moment in the multipolar expansion) is in general not equal to its
      Coulombic charge and it is not the integral of the renormalized charge
      distribution of the molecule. Moreover, as shown in this paper, the multipolar
      expansion of the Yukawa potential does not correspond, contrary to the case of
      the Coulomb potential, to its asymptotic expansion for large r. As a consequence,
      the charge term in the multipolar expansion is not the leading term in the
      asymptotic expansion. Instead, for large r values, multipoles of all orders
      contribute to the leading asymptotic term. Thus, the electrostatic potential
      from, for example, an electroneutral solvent molecule in an electrolyte solution
      has generally the same range as that from an ion. The proper asymptotic expansion
      for electrostatic interactions in electrolytes is derived. It is briefly shown
      how the multipole expansion formalism can also be applied in the Poisson
      Boltzmann approximation for primitive model electrolytes.

PMID- 17042583
TI  - Analytic calculation of the diagonal Born-Oppenheimer correction within
      configuration-interaction and coupled-cluster theory.
AB  - Schemes for the analytic calculation of the diagonal Born-Oppenheimer correction
      (DBOC) are formulated and implemented for use with general single-reference
      configuration-interaction and coupled-cluster wave function models. Calculations
      are reported to demonstrate the convergence of the DBOC with respect to electron
      correlation treatment and basis set as well as to investigate the size
      consistency error in configuration-interaction calculations of the DBOC. The
      importance of electron-correlation contributions to the DBOC is illustrated in
      the computation of the corresponding corrections for the reaction energy and
      activation barrier of the F + H2 --> FH + H reaction as well as of the
      atomization energy for trans-butadiene.

PMID- 17042584
TI  - Photodissociation dynamics of fluorobenzene (C6H5F) at 157 and 193 nm: Branching
      ratios and distributions of kinetic energy.
AB  - Following photodissociation of fluorobenzene (C6H5F) at 193 and 157 nm, we
      detected the products with fragmentation-translational spectroscopy by utilizing
      a tunable vacuum ultraviolet beam from a synchrotron for ionization. Between two
      primary dissociation channels observed upon irradiation at 193 (157) nm, the HF
      elimination channel C6H5F --> HF + C6H4 dominates, with a branching ratio of
      0.94+/-0.02 (0.61+/-0.05) and an average release of kinetic energy of 103 (108)
      kJ mol(-1); the H-elimination channel C6H5F --> H + C6H4F has a branching ratio
      of 0.06+/-0.02 (0.39+/-0.05) and an average release of kinetic energy of 18.6
      (26.8) kJ mol(-1). Photofragments H, HF, C6H4, and C6H4F produced via the one
      photon process have nearly isotropic angular distributions. Both the HF
      elimination and the H-elimination channels likely proceed via the ground-state
      electronic surface following internal conversion of C6H5F; these channels exhibit
      small fractions of kinetic energy release from the available energy, indicating
      that the molecular fragments are highly internally excited. We also determined
      the ionization energy of C6H4F to be 8.6+/-0.2 eV.

PMID- 17042585
TI  - The stability of allyl radicals following the photodissociation of allyl iodide
      at 193 nm.
AB  - The photodissociation of allyl iodide (C3H5I) at 193 nm was investigated by using
      a combination of vacuum-ultraviolet photoionization of the allyl radical,
      resonant multiphoton ionization of the iodine atoms, and velocity map imaging.
      The data provide insight into the primary C-I bond fission process and into the
      dissociative ionization of the allyl radical to produce C3H3+. The experimental
      results are consistent with the earlier results of Szpunar et al. [J. Chem. Phys.
      119, 5078 (2003)], in that some allyl radicals with internal energies higher than
      the secondary dissociation barrier are found to be stable. This stability results
      from the partitioning of available energy between the rotational and vibrational
      degrees of freedom of the radical, the effects of a centrifugal barrier along the
      reaction coordinate, and the effects of the kinetic shift in the secondary
      dissociation of the allyl radical. The present results suggest that the primary
      dissociation of allyl iodide to allyl radicals plus I*(2P(1/2)) is more important
      than previously suspected.

PMID- 17042586
TI  - Low frequency backbone vibrations of individual conformational isomers:
      tryptamine.
AB  - The low frequency vibrations of the ethylamino backbone of six conformers of
      tryptamine have been studied in the ground and excited states using dispersed
      fluorescence spectroscopy, rotationally resolved laser induced fluorescence, and
      ab initio calculations. Four low frequency vibrational modes of the backbone,
      which involve torsional and librational motions of the ethylamino group, have
      been identified. The three anti conformers show a substantially different
      vibrational pattern than the four conformers in which the amino group is in
      gauche position with respect to the pyrrole and the phenyl ring, respectively.

PMID- 17042587
TI  - Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone.
AB  - Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone (R-3MCP)
      is reported in the gas and liquid phases. Measurements of (2+1) resonance
      enhanced multiphoton ionization circular dichroism (REMPICD) for nozzle-jet
      expanded molecular beams of the equatorial conformer of R-3MCP are presented.
      Monitoring either mass-selected cations or photoelectrons produced via (2+1)
      REMPI through the n --> 3s Rydberg transition yielded a REMPICD of +1.5+/-0.5%
      [REMPICD identical with 2(I(L)-I(R))(I(L)+I(R))], where I(L/R) refers to the
      ion/electron signal for left/right circularly polarized light. A racemic mixture
      of 3-methylcyclopentanone showed no significant CD; however, the signal
      fluctuations were much larger than that observed for the resolved R-(+)-3
      methylcyclopentanone as might be expected for the small number of ions produced
      from slightly unequal numbers of enantiomers in each laser shot. Gas phase,
      vibrationally resolved, one-photon CD for vapor phase R-(+)-3
      methylcyclopentanone (i.e., admixture of five axial and equatorial forms) was
      measured to be approximately 0 and -0.004 at photon energies corresponding to the
      one- (nonresonant) and two-(3s resonance) photon energy levels. The one-photon CD
      (of the room temperature population of conformers) at an energy corresponding to
      the ionization step was measured previously to be approximately +0.0011 which is
      of the same sign as the REMPICD. The first step is also near a positive CD
      region. This suggests that the (2+1) REMPICD is determined primarily by both the
      initial and continuum steps. The one-photon CDs for the equatorial and axial
      forms of 3MCP are calculated, using GAUSSIAN03, to be approximately equal but
      having opposite sign for the transitions of interest. The CD for 3MCP in
      cyclohexane is found to be strongly temperature dependent as a result of the
      presence of both the axial and equatorial conformers. The energy difference
      between the two conformers is determined from a van't Hoff plot of these data to
      be 3.50+/-0.05 kJ/mole in cyclohexane and is approximately 1 kJ/mole smaller than
      measurements employing other methods.

PMID- 17042588
TI  - Effects of microsolvation on uracil and its radical anion: uracil(H2O)n (n = 1
      5).
AB  - Microsolvation effects on the stabilities of uracil and its anion have been
      investigated by explicitly considering the structures of complexes of uracil with
      up to five water molecules at the B3LYPDZP++ level of theory. For all five
      systems, the global minimum of the neutral cluster has a different equilibrium
      geometry from that of the radical anion. Both the vertical detachment energy
      (VDE) and adiabatic electron affinity (AEA) of uracil are predicted to increase
      gradually with the number of hydrating molecules, qualitatively consistent with
      experimental results from a photodetachment-photoelectron spectroscopy study [J.
      Schiedt et al., Chem. Phys. 239, 511 (1998)]. The trend in the AEAs implies that
      while the conventional valence radical anion of uracil is only marginally bound
      in the gas phase, it will form a stable anion in aqueous solution. The gas-phase
      AEA of uracil (0.24 eV) was higher than that of thymine by 0.04 eV and this gap
      was not significantly affected by microsolvation. The largest AEA is that
      predicted for uracil(H2O)5, namely, 0.96 eV. The VDEs range from 0.76 to 1.78 eV.

PMID- 17042589
TI  - Isotope effects in the infrared spectra of OCS-He complexes and clusters.
AB  - Infrared spectra of the OCS-He van der Waals complex and of OCS-He(N) clusters
      have been studied in the region of the OCS nu1 fundamental band using a tunable
      diode laser to probe a pulsed supersonic slit jet. For the complex, the spectrum
      of the normal isotope, 16O12C32S-4He, has been considerably extended and the 34S-
      and 13C-substituted forms have been recorded for the first time. The data could
      be analyzed satisfactorily using a conventional asymmetric rotor Hamiltonian with
      sextic centrifugal distortion terms. For the clusters, the 34S- and 13C
      substituted forms have been observed and assigned for N = 2-7, including some
      transitions with higher J values than previously reported for the normal isotope,
      e.g., R5. The observed vibrational shifts, relative to the free OCS molecule,
      were very similar to those of the normal isotope, and most of the difference
      could be explained by simple scaling. These results constitute a subtle and
      precise probe of intermolecular forces and dynamical effects in a system which is
      of current interest for cluster studies.

PMID- 17042590
TI  - Electron hydration dynamics in water clusters: A direct ab initio molecular
      dynamics approach.
AB  - Electron attachment dynamics of excess electron in water cluster (H2O)n (n = 2
      and 3) have been investigated by means of full-dimensional direct ab initio
      molecular dynamics (MD) method at the MP26-311++G(d,p) level. It was found that
      the hydrogen bond breaking due to the excess electron is an important process in
      the first stage of electron capture in water trimer. Time scale of electron
      localization and hydrogen bond breaking were determined by the direct ab initio
      MD simulation. The initial process of hydration in water cluster is clearly
      visualized in the present study. In n = 3, an excess electron is first trapped
      around the cyclic water trimer with a triangular form, where the excess electron
      is equivalently distributed on the three water molecules at time zero. After 50
      fs, the excess electron is concentrated into two water molecules, while the
      potential energy of the system decreases by -1.5 kcal/mol from the vertical
      point. After 100 fs, the excess electron is localized in one of the water
      molecules and the potential energy decreases by -5.3 kcal/mol, but the triangular
      form still remained. After that, one of the hydrogen bonds in the triangular form
      is gradually broken by the excess electron, while the structure becomes linear at
      100-300 fs after electron capture. The time scale of hydrogen bond breaking due
      to the excess electron is calculated to be about 300 fs. Finally, a dipole bound
      state is formed by the linear form of three water molecules. In the case of n =
      2, the dipole bound anion is formed directly. The mechanism of electron hydration
      dynamics was discussed on the basis of theoretical results.

PMID- 17042591
TI  - First-principles study of intermediate size silver clusters: Shape evolution and
      its impact on cluster properties.
AB  - Low-energy isomers of Ag(N) clusters are studied within gradient-corrected
      density functional theory over the size range of N = 9-20. The candidate
      conformations are drawn from an extensive structural database created in a recent
      exploration of Cu(N) clusters [M. Yang et al., J. Chem. Phys. 124, 24308 (2006)].
      Layered configurations dominate the list of the lowest-energy isomers of Ag(N)
      for N < 16. The most stable structures for N > 16 are compact with quasispherical
      shapes. The size-driven shape evolution is similar to that found earlier for
      Na(N) and Cu(N). The shape change has a pronounced effect on the cluster cohesive
      energies, ionization potentials, and polarizabilities. The properties computed
      for the most stable isomers of Ag(N) are in good agreement with the available
      experimental data.

PMID- 17042592
TI  - Theoretical investigation on 1H and 13C NMR chemical shifts of small alkanes and
      chloroalkanes.
AB  - Using density functional theory (DFT) with the B3LYP, PBE, and PBE0 exchange
      correlation functionals as well as the Moller-Plesset second-order perturbation
      theory (MP2) combined with a series of rather extended basis sets, 1H and 13C
      chemical shifts of small alkanes and chloroalkanes (with different numbers of
      chlorine atoms on specific positions) have been simulated and compared to
      experimental data. For the 1H chemical shifts, theory tends to reproduce
      experiment within the limits of the experimental errors. In the case of 13C
      chemical shift, the differences between theory and experiment increase
      monotonically with the number of chlorine atoms and exhibit a deviation from
      additivity. This behavior is related to the saturation of the experimental 13C
      chemical shifts with the number of chlorine atoms, whereas the evolution is
      mostly linear at both DFT and MP2 levels of approximation. This difference has
      been traced back to the relativistic spin-orbit coupling effects, which are
      exalted as a result of the enhancement of the s character of the C atom when
      increasing the number of linked Cl atoms. Thus, it was demonstrated that not only
      electron correlation but also relativistic effects have to be considered for
      estimating the 13C chemical shifts when several Cl atoms are directly attached to
      the C atom. Linear (theory/experiment) regressions have then been performed for
      the different types of C atoms, i.e., bearing one, two, and three Cl atoms, with
      excellent correlation coefficients. The linear correlation relationships so
      obtained can then serve to predict and facilitate the interpretation of the
      nuclear magnetic resonance spectra of more complex compounds. Furthermore, by
      investigating the basis set effects, the correlation between the chemical shifts
      calculated using the 6-311 + G(2d,p) basis set and the more extended 6-311 +
      G(2df,p) and aug-cc-pvtz basis sets is excellent, demonstrating that the choice
      of the 6-311 + G(2d,p) basis set for calculating the 1H and 13C chemical shifts
      is relevant.

PMID- 17042593
TI  - Rotational spectrum of cyanoacetylene solvated with helium atoms.
AB  - The high resolution microwave spectra of He(N)-HCCCN clusters were studied in the
      size ranges of 1-18 and 25-31. In the absence of an accompanying infrared study,
      rotational excitation energies were computed by the reptation quantum Monte Carlo
      method and used to facilitate the search and assignment of R(0) transitions from
      N > 6, as well as R(1) transitions with N > 1. The assignments in the range of 25
      31 are accurate to +/-2 cluster size units, with an essentially certain relative
      ordering. The rotational transition frequencies decrease with N = 1-6 and then
      show oscillatory behavior for larger cluster sizes, which is now recognized to be
      a manifestation of the onset and microscopic evolution of superfluidity. For
      cluster sizes beyond completion of the first solvation shell the rotational
      frequencies increase significantly above the large-droplet limit. This behavior,
      common to other linear molecules whose interaction with He features a strong
      nearly equatorial minimum, is analyzed using path integral Monte Carlo
      simulations. The He density in the incipient second solvation shell is shown to
      open a new channel for long permutation cycles, thus increasing the decoupling of
      the quantum solvent from the rotation of the dopant molecule.

PMID- 17042594
TI  - Jet cooled spectroscopy of H2DO+: Barrier heights and isotope-dependent tunneling
      dynamics from H3O+ to D3O+.
AB  - The first high resolution spectroscopic data for jet cooled H2DO+ are reported,
      specifically via infrared laser direct absorption in the OH stretching region
      with a slit supersonic jet discharge source. Transitions sampling upper (0-) and
      lower (0+) tunneling states for both symmetric (nu1+ <-- 0+, nu1- <-- 0-, and nu1
      <-- 0+) and antisymmetric (nu3+ <-- 0+ and nu3- <-- 0-) OH stretching bands are
      observed, where +/- refers to wave function reflection symmetry with respect to
      the planar umbrella mode transition state. The spectra can be well fitted to a
      Watson asymmetric top Hamiltonian, revealing band origins and rotational
      constants for benchmark comparison with high-level ab initio theory. Of
      particular importance are detection and assignment of the relatively weak band
      (nu1- <-- 0+) that crosses the inversion tunneling gap, which is optically
      forbidden in H3O+ or D3O+, but weakly allowed in H2DO+ by lowering of the
      tunneling transition state symmetry from D(3h) to C(2v). In conjunction with
      other H2DO+ bands, this permits determination of the tunneling splittings to
      within spectroscopic precision for each of the ground [40.518(10) cm(-1)], nu1 =
      1 [32.666(6) cm(-1)], and nu3 = 1 [25.399(11) cm(-1)] states. A one-dimensional
      zero-point energy corrected potential along the tunneling coordinate is
      constructed from high-level ab initio CCSD(T) calculations (AVnZ, n = 3,4,5) and
      extrapolated to the complete basis set limit to extract tunneling splittings via
      a vibrationally adiabatic treatment. Perturbative scaling of the potential to
      match splittings for all four isotopomers permits an experimental estimate of
      DeltaV0 = 652.9(6) cm(-1) for the tunneling barrier, in good agreement with full
      six-dimensional ab initio results of Rajamaki, Miani, and Halonen (RMH) [J. Chem.
      Phys. 118, 10929 (2003)]. (DeltaV0 (RMH) = 650 cm(-1)). The 30%-50% decrease in
      tunneling splitting observed upon nu1 and nu3 vibrational excitations arises from
      an increase in OH stretch frequencies at the planar transition state,
      highlighting the transition between sp2 and sp3 hybridizations of the OHD bonds
      as a function of inversion bending angle.

PMID- 17042595
TI  - Photodissociation of 1-bromo-2-butene, 4-bromo-1-butene, and cyclopropylmethyl
      bromide at 234 nm studied using velocity map imaging.
AB  - We present photofragment imaging experiments to characterize potential photolytic
      precursors of three C4H7 radical isomers: 1-methylallyl, cyclopropylmethyl, and 3
      buten-1-yl radicals. The experiments use 2+1 resonance enhanced multiphoton
      ionization (REMPI) with velocity map imaging to state-selectively detect the
      Br(2P(3/2)) and Br(2P(1/2)) atoms as a function of their recoil velocity imparted
      upon photodissociation of 1-bromo-2-butene, cyclopropylmethyl bromide, and 4
      bromo-1-butene at 234 nm as well as the angular distributions of the
      photofragments. Energy and momentum conservation allows the internal energy
      distribution of the nascent momentum-matched radicals to be derived. The radicals
      are detected with single photon photoionization at 157 nm. In the case of the 1
      methylallyl radical the photoionization cross section is expected to be
      independent of internal energy in the range of 7-30 kcal/mol. Thus, comparison of
      the product recoil kinetic energy distribution derived from the measurement of
      the 1-methylallyl velocity distribution, detecting the radicals with 157 nm
      photoionization, with a linear combination of the Br atom recoil kinetic energy
      distributions allows us to derive reliable REMPI line strength ratios for the
      detection of Br atoms and to test the assumption that the photoionization cross
      section does not strongly depend on the internal energy of the radical. This line
      strength ratio is then used to determine the branching to the Br(2P(3/2)) and
      Br(2P(1/2)) product channels for the other two photolytic systems and to
      determine the internal energy distribution of their momentum-matched radicals.
      (We also revisit earlier work on the photodissociation of cyclobutyl bromide
      which detected the Br atoms and momentum-matched cyclobutyl radicals.) This
      allows us to test whether the 157 nm photoionization of these radicals is
      insensitive to internal energy for the distribution of total internal
      (vibrational+rotational) energy produced. We find that 157 nm photoionization of
      cyclopropylmethyl radicals is relatively insensitive to internal energy, while 3
      buten-1-yl radicals show a photoionization cross section that is markedly
      dependent on internal energy with the lowest internal energy radicals not
      efficiently detected by photoionization at 157 nm. We present electronic
      structure calculations of the radicals and their cations to understand the
      experimental results.

PMID- 17042596
TI  - The lowest singlet-triplet excitation energy of BN: A converged coupled cluster
      perspective.
AB  - The notoriously small X 3Pi-a 1Sigma+ excitation energy of the BN diatomic has
      been calculated using high-order coupled cluster methods. Convergence has been
      established in both the one-particle basis set and the coupled cluster expansion.
      Explicit inclusion of connected quadruple excitations T4 is required for even
      semiquantitative agreement with the limit value, while connected quintuple
      excitations T5 still have an effect of about 60 cm(-1). Still higher excitations
      only account for about 10 cm(-1). Inclusion of inner-shell correlation further
      reduces Te by about 60 cm(-1) at the CCSDT, and 85 cm(-1) at the CCSDTQ level.
      Our best estimate, Te = 183+/-40 cm(-1), is in excellent agreement with earlier
      calculations and experiment, albeit with a smaller (and conservative)
      uncertainty. The dissociation energy of BN(X 3Pi) is De = 105.74+/-0.16 kcal/mol
      and D0 = 103.57+/-0.16 kcal/mol.

PMID- 17042597
TI  - Coupled-cluster studies of the electronic excitation spectra of silanes.
AB  - The electronic excitation spectra of unsubstituted linear silanes (n
      Si(m)H(2m+2), m = 1-6), cyclopentasilane (c-Si5H10), and neopentasilane (neo
      Si5H12) have been studied at the coupled-cluster approximate singles and doubles
      (CC2) level using Dunning's quadruple-zeta basis sets augmented with diffuse
      functions (aug-cc-pVQZ). Comparisons with measured ultraviolet spectra for Si2H6
      and n-Si3H8 show that CC2 calculations using these basis sets yield excitation
      energies in good agreement with experiment. The calculated excitation thresholds
      for Si2H6 and n-Si3H8 of 7.61 and 6.68 eV are only 0.05 eV larger than the gas
      phase values of 7.56 and 6.63 eV, respectively. For n-Si4H10, n-Si5H12, and neo
      Si5H12, the calculated excitation thresholds of 6.51, 6.14, and 6.87 eV for the
      lowest dipole-allowed transitions are about 0.4 eV larger than the corresponding
      liquid-phase data of 6.05, 5.77, and 6.53 eV; the discrepancy can mainly be
      attributed to solvent effects. The obtained excitation thresholds for n-Si6H14 is
      5.85 eV, whereas no experimental data are available for its optical gap.
      Calculations using the Karlsruhe triple-zeta valence basis sets augmented with
      single and double sets of polarization functions show that very large basis sets
      augmented with diffuse functions are needed for obtaining accurate excitation
      energies. The optical gaps for silanes obtained using the triple-zeta
      polarization basis sets were found to be 0.4 and 0.2 eV larger than those
      obtained using Dunning's quadruple-zeta basis sets. Excitation thresholds
      calculated at density functional theory levels using generalized gradient
      approximation are 0.7-1.0 eV smaller than the experimental values and by
      employing hybrid functionals they are 0.3-0.4 eV below the experimental
      thresholds. By adding the present basis-set correction and environmental effects
      to the previously calculated CC2 value for the excitation threshold of the
      Si29H36 silicon nanocluster, the extrapolated absorption threshold is 4.0 eV as
      compared to the recently reported experimental value of 3.7 eV.

PMID- 17042598
TI  - Photodissociation dynamics of vinyl fluoride (CH2CHF) at 157 and 193 nm:
      Distributions of kinetic energy and branching ratios.
AB  - Using photofragment translational spectroscopy and tunable vacuum-ultraviolet
      ionization, we measured the time-of-flight spectra of fragments upon
      photodissociation of vinyl fluoride (CH2CHF) at 157 and 193 nm. Four primary
      dissociation pathways--elimination of atomic F, atomic H, molecular HF, and
      molecular H2--are identified at 157 nm. Dissociation to C2H3 + F is first
      observed in the present work. Decomposition of internally hot C2H3 and C2H2F
      occurs spontaneously. The barrier heights of CH2CH --> CHCH + H and cis-CHCHF -->
      CHCH + F are evaluated to be 40+/-2 and 44+/-2 kcal mol(-1), respectively. The
      photoionization yield spectra indicate that the C2H3 and C2H2F radicals have
      ionization energies of 8.4+/-0.1 and 8.8+/-0.1 eV, respectively. Universal
      detection of photoproducts allowed us to determine the total branching ratios,
      distributions of kinetic energy, average kinetic energies, and fractions of
      translational energy release for all dissociation pathways of vinyl fluoride. In
      contrast, on optical excitation at 193 nm the C2H2 + HF channel dominates whereas
      the C2H3 + F channel is inactive. This reaction C2H3F --> C2H2 + HF occurs on the
      ground surface of potential energy after excitation at both wavelengths of 193
      and 157 nm, indicating that internal conversion from the photoexcited state to
      the electronic ground state of vinyl fluoride is efficient. We computed the
      electronic energies of products and the ionization energies of fluorovinyl
      radicals.

PMID- 17042599
TI  - Microscopic simulations of molecular cluster decay: Does the carrier gas affect
      evaporation?
AB  - We develop a kinetic theory of cluster decay by considering the stochastic motion
      of molecules within an effective potential of mean force (PMF) due to the
      cluster. We perform molecular dynamics simulations on a 50-atom argon cluster to
      determine the mean radial force on a component atom and hence the confining
      potential of mean force. Comparisons between isolated clusters and clusters
      thermostatted through the presence of a 100-atom helium carrier gas show that the
      heat bath has only a slight effect upon the PMF. This confirms the validity of
      calculations of cluster properties using isolated cluster simulations. The PMF is
      used to calculate the atomic evaporation rate from these clusters, and results
      are compared with the predictions of the capillarity approximation together with
      detailed balance, both components of the classical theory of aerosol nucleation.

PMID- 17042600
TI  - Counterpoise corrected geometries of hydrated complexes.
AB  - We have calculated the equilibrium geometries of the hydrated complexes, H2O.CO2,
      H2O.CS2,H2O.OCS, H2O.SO2, and H2O.SO3, in the electronic ground state. We have
      used the coupled cluster with singles, doubles, and perturbative triples ab
      initio method with a correlation consistent augmented triple-zeta basis set. We
      find that a counterpoise corrected optimization scheme is important for an
      accurate description of the geometries. These high level ab initio calculated
      geometries are of comparable quality to those obtained experimentally.

PMID- 17042601
TI  - S(1D2) atomic orbital polarization in the photodissociation of OCS at 193 nm:
      Construction of the complete density matrix.
AB  - The absolute velocity-dependent alignment and orientation for S(1D2) atoms from
      the photodissociation of OCS at 193 nm were measured using the dc slice imaging
      method. Three main peaks ascribed to specific groups of high rotational levels of
      CO in the vibrational ground state were found, with rotationally resolved rings
      in a fourth slow region ascribed to weak signals associated with excited
      vibrational states of CO. The observed speed-dependent beta and polarization
      parameters support the interpretation that there are two main dissociation
      processes: a simultaneous two-surface (A' and A") excitation and the initial
      single-surface (A') excitation followed by the nonadiabatic crossing to ground
      state. At 193 nm photodissociation, the nonadiabatic dissociation process is
      strongly enhanced relative to longer wavelengths. The angle- and speed-dependent
      S(1D2) density matrix can be constructed including the higher order (K = 3,4)
      contributions for the circularly polarized dissociation light. This was
      explicitly done for selected energies and angles. It was found in one case that
      the density matrix is sensitively affected by the rank 4 terms, suggesting that
      the higher order contributions should not be overlooked for an accurate picture
      of the dissociation dynamics in this system.

PMID- 17042602
TI  - Electronic spectroscopy of NO-(Rg)x complexes (Rg = Ne,Ar) via the 4s and 3d
      Rydberg states.
AB  - We have employed (2 + 1) resonance enhanced multiphoton ionization spectroscopy
      to investigate the 3d and 4s Rydberg states of the NO molecule when bound to the
      surface of Rg(x) clusters (Rg = rare gas). We observe that the spectra of the NO
      Ar(x) species converge in appearance as x increases, and this is discussed in
      terms of two Rg atoms interacting with the NO+ core, with other Rg atoms being
      "outside" the Rydberg orbital. We show that the interaction of each of the Rg
      atoms with the NO is essentially independent for the NO-Rg2 complexes: both by
      comparing our spectra for Rydberg states of NO-Rg and NO-Rg2, and from the
      results of ab initio calculations on NO+ - Rg and NO+ - Rg2. In addition, we
      discuss the disappearance of some electronic bands upon complexation in terms of
      Franck-Condon factors that are very sensitive to the angular coordinate. We
      relate our results to those of the bulk by comparing to the previously reported
      electronic spectroscopy of NO in both Rg matrices and He nanodroplets.

PMID- 17042603
TI  - Size effects in the infrared spectra of NH3 ice nanoparticles studied by a
      combined molecular dynamics and vibrational exciton approach.
AB  - Infrared extinction spectra of ammonia ice nanoparticles with radii between 2 and
      10 nm show pronounced band shape variations depending on the conditions of
      particle formation by collisional cooling. We present experimental and
      theoretical evidence showing that the variations in the region of the nu2
      (umbrella) fundamental are due to changes in the particle size. The effect is
      analyzed in terms of an explicit atomistic model of the particles' structure and
      vibrational dynamics. An explicit potential function combined with a novel
      extension of the vibrational exciton approach allows us to simulate extinction
      spectra for particles containing up to 16,000 atoms. It is shown that the
      particles formed under the conditions of our experiments consist of a crystalline
      core surrounded by an amorphous shell with an approximately constant thickness of
      1-2 nm. For the nu2 fundamental, this shell gives rise to a broad band [full
      width at half maximum (FWHM) 72 cm(-1)] blueshifted by about 19 cm(-1) relative
      to a narrow peak (FWHM of 19 cm(-1)) which arises from the crystalline core.

PMID- 17042604
TI  - Effect of donor-acceptor interaction strength on excitation energy migration and
      diffusion at high donor concentrations.
AB  - The migration and diffusion modulated excitation energy transfer has been studied
      in a new dye pair 7-diethylamino-4-methylcoumarin (donor) to 3,3'
      dimethyloxacarbocyanine iodide (acceptor) by steady-state and picosecond time
      resolved spectroscopy. To reduce the artifact of self-absorption, at high donor
      concentrations, the time-resolved studies have been carried out in thin films of
      polyvinyl alcohol (solid matrix) and in methanol (liquid phase) at front-face
      geometry of excitation. The Forster-type (nonradiative) energy transfer [Discuss.
      Faraday Soc. 27, 7 (1959)] takes place directly from donor to acceptor in case of
      solid matrix, while Yokota-Tanimoto model [J. Phys. Soc. Jpn. 22, 779 (1967)] for
      diffusion has been found to be operating in the liquid phase. It has been found
      here that the high interaction strength between donor and acceptor molecules as
      compared to that among donors masks the effect of energy migration and diffusion
      at high donor concentrations. The rate and efficiency of energy transfer increase
      with increasing the acceptor concentration. This has been confirmed by the study
      of acceptor kinetics.

PMID- 17042605
TI  - Supercooling of aqueous NaCl and KCl solutions under acoustic levitation.
AB  - The supercooling capability of aqueous NaCl and KCl solutions is investigated at
      containerless state by using acoustic levitation method. The supercooling of
      water is obviously enhanced by the alkali metal ions and increases linearly with
      the augmentation of concentrations. Furthermore, the supercooling depends on the
      nature of ions and is 2-3 K larger for NaCl solution than that for KCl solution
      in the present concentration range: Molecular dynamics simulations are performed
      to reveal the intrinsic correlation between supercoolability and microstructure.
      The translational and orientational order parameters are applied to
      quantitatively demonstrate the effect of ionic concentration on the hydrogen-bond
      network and ice melting point. The disrupted hydrogen-bond structure determines
      essentially the concentration dependence of supercooling. On the other hand, the
      introduced acoustic pressure suppresses the increase of supercooling by promoting
      the growth and coalescence of microbubbles, the effective nucleation catalysts,
      in water. However, the dissolved ions can weaken this effect, and moreover the
      degree varies with the ion type. This results in the different supercoolability
      for NaCl and KCl solutions under the acoustic levitation conditions.

PMID- 17042606
TI  - Theoretical direct correlation function for two-dimensional fluids of
      monodisperse hard spheres.
AB  - The direct correlation function plays an important role in describing the effects
      of the structure of particle systems with respect to light diffraction, x-ray
      diffraction as well as transmission and transmission fluctuations of radiation
      through a dense suspension. In this paper, the direct correlation function for a
      monolayer of monodisperse hard spheres or disks is derived theoretically. Based
      on the approximation of Baus and Colot [Phys. Rev. A 36, 3912 (1987)] and the
      equation of state for a fluid of hard disks by Santos et al. [J. Chem. Phys. 103,
      4622 (1995)], we propose a new direct correlation function, which compares well
      to the approximate analytical expressions and gives a good prediction of the
      structure factor in a wide range of monolayer density or suspension
      concentration. The resulting radial distribution function also agrees well with
      Monte Carlo computer simulation data. The corresponding contact values of the
      radial distribution function compare well with the results of analytic
      approximations, numerical solutions, and computer simulations. Our proposed
      direct correlation function is applied to the transmission fluctuation
      spectrometric study. Experimental results show good agreement with the theory.

PMID- 17042607
TI  - Scaling fields and pressure mixing in the Widom-Rowlinson model.
AB  - We address the issues of scaling fields and of pressure mixing in the penetrable
      sphere model. This model has an exact symmetry locus from which analytical
      results may be derived. Based on exact results, we demonstrate that the scaling
      fields are analytic functions of temperature and chemical potential only. We
      conclude that there is no pressure mixing in this model. Our findings are in
      accord with numerical simulations for the same model.

PMID- 17042608
TI  - Expressions for the stress and elasticity tensors for angle-dependent potentials.
AB  - The stress and elasticity tensors for interatomic potentials that depend
      explicitly on bond bending and dihedral angles are derived by taking strain
      derivatives of the free energy. The resulting expressions can be used in Monte
      Carlo and molecular dynamics simulations in the canonical and microcanonical
      ensembles. These expressions are particularly useful at low temperatures where it
      is difficult to obtain results using the fluctuation formula of Parrinello and
      Rahman [J. Chem. Phys. 76, 2662 (1982)]. Local elastic constants within
      heterogeneous and composite materials can also be calculated as a function of
      temperature using this method. As an example, the stress and elasticity tensors
      are derived for the second-generation reactive empirical bond-order potential.
      This potential energy function was used because it has been used extensively in
      computer simulations of hydrocarbon materials, including carbon nanotubes, and
      because it is one of the few potential energy functions that can model chemical
      reactions. To validate the accuracy of the derived expressions, the elastic
      constants for diamond and graphite and the Young's Modulus of a (10,10) single
      wall carbon nanotube are all calculated at T = 0 K using this potential and
      compared with previously published data and results obtained using other
      potentials.

PMID- 17042609
TI  - Changes of relaxation dynamics of a hydrogen-bonded glass former after removal of
      the hydrogen bonds.
AB  - Dielectric relaxation spectra of two closely related glass formers, dipropylene
      glycol [H-(C3H6O)2-OH] and dipropylene glycol dimethyl ether [CH3-O-(C3H6O)2
      CH3], were measured at ambient and elevated pressures in the supercooled and the
      glassy states are presented. Hydrogen bonds formed in dipropylene glycol are
      removed when its ends are replaced by two methyl groups to become dipropylene
      glycol dimethyl ether. In the process, the primary relaxation, the excess wing,
      and the resolved secondary relaxation of dipropylene glycol are all modified when
      the structure is transformed to become dipropylene glycol dimethyl ether. The
      modifications include the pressure and temperature dependences of these
      relaxation processes and their interrelations. Thus, by comparing the dielectric
      spectra of these two closely related glass formers at ambient and elevated
      pressures, the differences in the relaxation dynamics and properties in the
      presence and absence of hydrogen bonding are identified.

PMID- 17042610
TI  - Origins of linewidth in 1H magic-angle spinning NMR.
AB  - A detailed study of the factors determining the linewidth (and hence resolution)
      in 1H solid-state magic-angle spinning NMR is described. Although it has been
      known from the early days of magic-angle spinning (MAS) that resolution of
      spectra from abundant nuclear spins, such as 1H, increases approximately linearly
      with increasing sample rotation rate, the difficulty of describing the dynamics
      of extended networks of coupled spins has made it difficult to predict a priori
      the resolution expected for a given sample. Using recently developed, highly
      efficient methods of numerical simulation, together with experimental
      measurements on a variety of test systems, we propose a comprehensive picture of
      1H resolution under MAS. The "homogeneous" component of the linewidth is shown to
      depend primarily on the ratio between an effective local coupling strength and
      the spin rate, modified by geometrical factors which loosely correspond to the
      "dimensionality" of the coupling network. The remaining "inhomogeneous" component
      of the natural linewidth is confirmed to have the same properties as in dilute
      spin NMR. Variations in the NMR frequency due to chemical shift effects are shown
      to have minimal impact on 1H resolution. The implications of these results for
      solid-state NMR experiments involving 1H and other abundant-spin nuclei are
      discussed.

PMID- 17042611
TI  - Relationships between three-body and two-body interactions in fluids and solids.
AB  - Molecular dynamics data are reported for two-body and three-body interactions in
      noble gases at densities covering the gas, liquid, and solid phases. The data
      indicate that simple relationships exist between three- and two-body interactions
      in both fluid and solid phases. The relationship for liquids has a simple density
      dependence with only one external parameter. In contrast, the solid phase
      relationship depends both on density and on the square of density and requires
      the evaluation of two parameters. The relationships are tested for both system
      size and temperature dependences. The values of the relationship parameters are
      only sensitive to system size when a small number of atoms are involved. For 500
      or more atoms, they remain nearly constant. The relationships are valid for both
      subcritical and slightly supercritical temperatures. A practical benefit of the
      relationships is that they enable the use of two-body intermolecular potentials
      for the prediction of the properties of real systems without the computational
      expense of three-body calculations.

PMID- 17042612
TI  - Neutron powder diffraction studies of sulfuric acid hydrates. I. The structure of
      sulfuric acid hemitriskaidekahydrate D2SO4.6(1/2)D2O.
AB  - We report the first neutron diffraction data from D2SO4.6(1/2)D2O. The crystal is
      monoclinic, space group Cm, with four formula units per unit cell. At 4.2 K the
      unit cell dimensions are a = 6.253 26(4) A, b = 26.813 62(10) A, c = 5.908 45(2)
      A, and beta = 112.1939(3) degrees [V = 917.286(6) A3 and rho(deuterated) =
      1664.14(2) kg m(-3)]. The deuteron positions refined from the neutron data are in
      agreement with those established by single crystal x-ray analysis [D. Mootz and
      A. Merschenz-Quack, Z. Naturforsch. B 42, 1231 (1987)], but not with those found
      from the ab initio simulation of Hirsch and Ojamae [Acta Crystallogr, Sect. B:
      Struct. Sci. 60, 179 (2004)]. The crystal consists of SO4(2-), D3O+ ions, and D2O
      molecules hydrogen bonded to form a layered structure in which sheets of
      "icelike" D3O+ and D2O are separated by layers of opposing SO4(2-) tetrahedra.

PMID- 17042613
TI  - Competition between ultrafast relaxation and photoionization in excited
      prefluorescent states of tryptophan and indole.
AB  - The quantum yield of photoionization of TrpH and IndH from the nonrelaxed
      prefluorescent state S* increases with the temperature decrease. This effect is
      attributed to the competition between temperature independent ionization and
      ultrafast thermal relaxation S* --> S1. The rate constant of the relaxation does
      not depend on the solvent and on the presence of the amino acid side chain: the
      temperature dependences of photoionization quantum yield, obtained for TrpH and
      IndH in different solvents, practically coincide. The activation energy for the
      relaxation rate constant Er approximately 4.5 kJ/mol probably corresponds to
      intramolecular process or to the formation of the vibronically excited transient
      complex between photoexcited molecule and solvent molecules.

PMID- 17042614
TI  - Orientational dynamics of isotopically diluted H2O and D2O.
AB  - We use femtosecond midinfrared pump-probe spectroscopy to compare the ultrafast
      dynamics of HDO dissolved in D2O and H2O. For both systems the vibrational energy
      relaxation proceeds through an intermediate state. The relaxation leads to
      heating of the sample, which is observed in the transient spectra. In order to
      obtain the correct anisotropy decay, the ingrowing heating signal is subtracted
      from the raw data. For the OD vibration this procedure works well. For the OH
      vibration, however, we find an additional effect that leads to a severe
      distortion of the anisotropy. We show that this effect can be explained by a
      slightly faster reorientation of excited molecules during their relaxation as
      compared to unexcited molecules. We construct a model that includes this effect
      and is able to reproduce the experimental data. Using this model we show how the
      distorted anisotropy can be corrected.

PMID- 17042615
TI  - Dynamical properties of the soft sticky dipole-quadrupole-octupole water model: a
      molecular dynamics study.
AB  - The dynamical properties of the soft sticky dipole-quadrupole-octupole (SSDQO)
      water model using SPC/E moments are calculated utilizing molecular dynamics
      simulations. This new potential for liquid water describes the water-water
      interactions by a Lennard-Jones term and a sticky potential, which is an
      approximate moment expansion with point dipole, quadrupole, and octupole moments,
      and reproduces radial distribution functions of pure liquid water using the
      moments of SPC/E [Ichiye and Tan, J. Chem. Phys. 124, 134504 (2006)]. The forces
      and torques of SSDQO water for the dipole-quadrupole, quadrupole-quadrupole, and
      dipole-octupole interactions are derived here. The simulations are carried out at
      298 K in the microcanonical ensemble employing the Ewald method for the long
      range dipole-dipole interactions. Here, various dynamical properties associated
      with translational and rotational motions of SSDQO water using the moments of
      SPC/E (SSDQO:SPC/E) water are compared with the results from SPC/E and also
      experiment. The self-diffusion coefficient of SSDQO:SPC/E water is found to be in
      excellent agreement with both SPC/E and experiment whereas the single particle
      orientational relaxation time for dipole vector is better than SPC/E water but it
      is somewhat smaller than experiment. The dielectric constant of SSDQO:SPC/E is
      essentially identical to SPC/E, and both are slightly lower than experiment.
      Also, molecular dynamics simulations of the SSDQO water model are found to be
      about twice as fast as three-site models such as SPC/E.

PMID- 17042616
TI  - Identification and properties of the 1La and 1Lb states of pyranine.
AB  - The spectroscopic locations of the 1La and 1Lb electronic states of pyranine (1
      hydroxy-3,6,8-pyrenetrisulfonic acid, commonly referred to as HPTS), as well as
      several related compounds, are found using magnetic circular dichroism
      spectroscopy as well as absorption and fluorescence spectroscopies. These
      electronic states have been discussed in connection with the photoacid properties
      of HPTS. Polarization selective fluorescence spectroscopy is used to identify the
      transition dipole directions of the electronic states of the compounds studied.
      The issue of the origin for the changes in vibronic structure of HPTS in
      different solvents is addressed. It is demonstrated that a Brownian oscillator
      model, in which the strength of the coupling of the electronic states to the
      solvent changes with solvent, is sufficient to reproduce the trends in the shapes
      of the vibronic structure.

PMID- 17042617
TI  - Homogeneous nucleation at high supersaturation and heterogeneous nucleation on
      microscopic wettable particles: A hybrid thermodynamic/density-functional theory.
AB  - Homogeneous nucleation at high supersaturation of vapor and heterogeneous
      nucleation on microscopic wettable particles are studied on the basis of Lennard
      Jones model system. A hybrid classical thermodynamics and density-functional
      theory (DFT) approach is undertaken to treat the nucleation problems. Local
      density approximation and weighted-density approximation are employed within the
      framework of DFT. Special attention is given to the disjoining pressure of small
      liquid droplets, which is dependent on the thickness of wetting film and radius
      of the wettable particle. Different contributions to the disjoining pressure are
      examined using both analytical estimations and numerical DFT calculation. It is
      shown that van der Waals interaction results in negative contribution to the
      disjoining pressure. The presence of wettable particles results in positive
      contribution to the disjoining pressure, which plays the key role in the
      heterogeneous nucleation. Several definitions of the surface tension of liquid
      droplets are discussed. Curvature dependence of the surface tension of small
      liquid droplets is computed. The important characteristics of nucleation,
      including the formation free energy of the droplet and nucleation barrier height,
      are obtained.

PMID- 17042618
TI  - A mechanical representation of entropy for a large finite system.
AB  - The temporal evolution of the entropy of a mechanical system as described by a
      single trajectory is computed using the Clausius [Philos. Mag. 40, 122 (1868)]
      equality. This requires computing the maximal work that can be done by the system
      and comparing it to the actual work performed. A single trajectory suffices to
      determine the entropy when it is "typical," meaning that average values of
      mechanical variables will not be different when computed using trajectories with
      different initial conditions. The results are illustrated for small rare gas
      clusters heated and compressed by an impact at a hard surface.

PMID- 17042619
TI  - Dielectric study on the flow alignment in 4-n-pentyl-4'-cyanobiphenyl.
AB  - Dielectric permittivity and loss are measured under steady shear flow as
      functions of temperature, shear rate, electric field frequency, and electric
      field strength in the nematic (N) and the isotropic (I) phases of 4-n-pentyl-4'
      cyanobiphenyl. In the N phase, the dielectric permittivity in the quiescent state
      is largely modified if the steady shear flow is applied. These behaviors are
      discussed based on the Leslie-Ericksen theory [Q. J. Mech. Appl. Math. 19, 357
      (1966); Arch. Ration. Mech. Anal. 4, 231 (1960)], showing that the dielectric
      properties under the shear flow are consistently interpreted in terms of the flow
      alignment of the director, a unit vector specifying the orientation of the liquid
      crystals. It is also suggested that the behaviors of dielectric permittivities
      are similar to those of the viscosities.

PMID- 17042620
TI  - Improvement on macroscopic compressibility approximation and beyond.
AB  - A numerical procedure is proposed to extend the thermodynamic perturbation
      expansion (TPE) to a higher order. It is shown that the present second order term
      is superior to that due to a macroscopic compressibility approximation (MCA), a
      local compressibility approximation, and a superposition approximation by Barker
      and Henderson [Rev. Mod. Phys. 48, 587 (1976)]. Extensive model calculation and
      comparison with simulation data available in literature and supplied in the
      present report indicate that the present third order TPE is superior to a
      previous second order TPE based on the MCA, two previous perturbation theories,
      which are respectively based on an analytical mean spherical approximation for an
      Ornstein-Zernike equation, and an assumed explicit functional form for the
      Laplace transform of radial distribution function multiplied by radial distance,
      and a recent generalized van der Waals theory. The present critical temperature
      for a hard core attractive Yukawa fluid of varying range is in very good
      agreement with that due to a hierarchical reference theory. The present third
      order TPE is computationally far more modest than the self-consistent integral
      equation theory, and therefore is a viable alternative to use of the latter.

PMID- 17042621
TI  - Hydrogen bonding and induced dipole moments in water: predictions from the
      Gaussian charge polarizable model and Car-Parrinello molecular dynamics.
AB  - We compare a new classical water model, which features Gaussian charges and
      polarizability (GCPM) with ab initio Car-Parrinello molecular dynamics (CPMD)
      simulations. We compare the total dipole moment, the total dipole moment
      distribution, and degree of hydrogen bonding at ambient to supercritical
      conditions. We also compared the total dipole moment calculated from both the
      electron density (partitioning the electron density among molecules based on a
      zero electron flux condition), and from the center of localized Wannier function
      centers (WFCs). Compared to CPMD, we found that GCPM overpredicts the dipole
      moment derived by partitioning the electron density and underpredicts that
      obtained from the WFCs, but exhibits similar trends and distribution of values.
      We also found that GCPM predicted similar degrees of hydrogen bonding compared to
      CPMD and has a similar structure.

PMID- 17042622
TI  - Water mediated attraction between repulsive ions: a cluster-based simulation
      approach.
AB  - Could two like ions be attractive to each other in the presence of water? To
      address this question and to further interrogate the intriguing solvent effects
      at a molecular level on multiply charged species, a "bottom-up" simulation
      approach was formulated, from which the inter-ionic potential of mean force and
      other properties were monitored closely with the gradual addition of the water
      molecules. This approach was first tested on a commonly studied ion pair (namely,
      Na+ and Cl-), where excellent agreement with the published bulk-phase data was
      found. Further application of this approach to the like-ion pair indicated that
      an attractive interaction between two anions or two cations can be induced by the
      addition of an appropriate number of water molecules. This result corroborates a
      recent experimental report of an intriguing folding of a dianionic polymer into a
      more compact structure with the addition of water molecules in gas phase as well
      as previous theoretical findings of possible attraction between like-ion pairs in
      bulk aqueous phases.

PMID- 17042623
TI  - Detection of multiple-quantum coherences with projective nuclear magnetic
      resonance measurement.
AB  - It is shown that in nuclear magnetic resonance, multiple-quantum (MQ) coherences
      can be detected "instantly" by exploiting the principle of quantum-mechanical
      projective measurement. Therefore, the mixing period, which involves collective
      multispin dynamics and converts MQ coherences into observable single-quantum
      coherence (magnetization), is not necessary. The experimental examples are given
      for two finite clusters: benzene in liquid crystal and liquid crystal 4'-n-pentyl
      4-cyanobiphenyl, and for solid adamantane with an infinite network of dipolar
      couplings.

PMID- 17042624
TI  - Extended spin-boson model for nonadiabatic hydrogen tunneling in the condensed
      phase.
AB  - A nonadiabatic rate expression for hydrogen tunneling reactions in the condensed
      phase is derived for a model system described by a modified spin-boson
      Hamiltonian with a tunneling matrix element exponentially dependent on the
      hydrogen donor-acceptor distance. In this model, the two-level system
      representing the localized hydrogen vibrational states is linearly coupled to the
      donor-acceptor vibrational mode and the harmonic bath. The Hamiltonian also
      includes bilinear coupling between the donor-acceptor mode and the bath
      oscillators. This coupling provides a mechanism for energy exchange between the
      two-level system and the bath through the donor-acceptor mode, thereby
      facilitating convergence of the time integral of the probability flux correlation
      function for the case of weak coupling between the two-level system and the bath.
      The dependence of the rate constant on the model parameters and the temperature
      is analyzed in various regimes. Anomalous behavior of the rate constant is
      observed in the weak solvation regime for model systems that lack an effective
      mechanism for energy exchange between the two-level system and the bath. This
      theoretical formulation is applicable to a wide range of chemical and biological
      processes, including neutral hydrogen transfer reactions with small solvent
      reorganization energies.

PMID- 17042625
TI  - Hole localization in Al doped silica: A DFT + U description.
AB  - Despite density functional theory (DFT) being the most widely used ab initio
      approach for studying the properties of oxide materials, the modeling of
      localized hole states in doped or defective oxides can be a challenge. The
      electronic hole formed when silica is doped with aluminum is such a defect, for
      which a DFT description of the atomic and electronic structures has previously
      been found to be inconsistent with experiment, while Hartree-Fock provides a
      consistent description. We have applied the DFT + U approach to this problem and
      find that the structural distortions around the dopant are consistent with
      experimental data as well as earlier cluster calculations using Hartree-Fock and
      perturbation theory. A hole state is found 1.1 eV (1.6 eV experimentally) above
      the top of the valence band with localization of spin on the oxygen atom which
      shows the elongated Al-O distance. A formation energy of 5.7 eV is found. We
      discuss implications for using DFT+U to model defective oxide systems with O 2p
      holes.

PMID- 17042626
TI  - Freezing of hard spheres confined in narrow cylindrical pores.
AB  - Monte Carlo simulations for the equation of state and phase behavior of hard
      spheres confined inside very narrow hard tubes are presented. For pores whose
      radii are greater than 1.1 hard sphere diameters, a sudden change in the density
      and the microscopic structure of the fluid is neatly observed, indicating the
      onset of freezing. In the high-density structure the particles rearrange in such
      a way that groups of three particles fit in sections across the pore.

PMID- 17042627
TI  - Evidence of meniscus interface transport in dip-pen nanolithography: An annular
      diffusion model.
AB  - Ring shaped dots were patterned with mercaptohexadecanoic acid ink by dip-pen
      nanolithography. These dots have an ink-free inner core surrounded by an inked
      annular region, making them different from the filled dots usually obtained. This
      suggests a different transport mechanism than the current hypothesis of bulk
      water meniscus transport. A meniscus interface ink transport model is proposed,
      and its general applicability is demonstrated by predicting the patterned dot
      radii of chemically diverse inks.

PMID- 17042628
TI  - Kinetics of droplet condensation through a double free-energy barrier.
AB  - Results are presented for the kinetics of nucleation of liquid droplets from a
      one-component vapor phase on a planar lyophobic substrate patterned with a large
      number of easily wettable (lyophilic) circular domains. If the wettability of
      these lyophilic domains is characterized by a contact angle smaller than pi2, for
      intermediate values of the supersaturation, the condensation of a droplet on a
      lyophilic domain occurs through a free-energy barrier with two maxima, that is,
      through a double barrier. A simple model is proposed for the kinetics of droplet
      condensation through a double barrier that combines Kramers's [Physica (Utrecht)
      7, 284 (1940)] transition rate theory with known results of nucleation theory. In
      the framework of this model, the solution is derived for the steady-state limit
      of the nucleation process. The number of lyophilic domains available for droplet
      condensation reduces with time as domains are occupied by droplets. The problem
      of droplet condensation through a double barrier is solved taking into account
      the effect of the time-dependent depletion in the number of available lyophilic
      domains.

PMID- 17042629
TI  - Low sticking probability in the nonactivated dissociation of N2 molecules on
      W(110).
AB  - The six-dimensional potential energy surface for the dissociation of N2 molecules
      on the W(110) surface has been determined by density functional calculations and
      interpolated using the corrugation reducing procedure. Examination of the
      resulting six-dimensional potential energy surface shows that nonactivated paths
      are available for dissociation. In spite of this, the dissociation probability
      goes to a very small value when the impact energy goes to zero and increases with
      increasing energy, a behavior usually associated with activated systems.
      Statistics on the dynamics indicate that this unconventional result is a
      consequence of the characteristics of the potential energy surface at long
      distances. Furthermore, two distinct channels are identified in the dissociation
      process, namely, a direct one and an indirect one. The former is responsible for
      dissociation at high energies. The latter, which includes long-lasting dynamic
      trapping in the vicinity of a potential well above the W top position, is the
      leading mechanism at low and intermediate energies.

PMID- 17042630
TI  - O2-coverage-dependent CO oxidation on reduced TiO2(110): A first principles
      study.
AB  - First principles periodic slab calculations based on gradient-corrected density
      functional theory have been performed to investigate CO oxidation on rutile
      TiO2(110) at varying O2 coverages (theta = 1, 2, and 3, where theta is defined as
      the number of O2 per oxygen vacancy). For each coverage we only present the
      reaction of CO with oxygen species in the most stable configuration. Our results
      show a significant variation in the oxidation activation energy with O2 coverage.

PMID- 17042631
TI  - Colloidal electroconvection in a thin horizontal cell. II. Bulk electroconvection
      of water during parallel-plate electrolysis.
AB  - We recently have reported [J. Chem. Phys. 122, 164701 (2005)] a family of
      electroconvective patterns that arise when charge-stabilized colloidal
      dispersions are driven by constant (dc) vertical electric fields. Competition
      between gravity and electrokinetic forces acting on the individual spheres in
      this system leads to the formation of highly organized convective instabilities
      involving hundreds of spheres. Here, we report a distinct class of
      electroconvective patterns that emerge in confined aqueous dispersions at higher
      biases. These qualitatively resemble the honeycomb and labyrinthine patterns
      formed during thermally driven Rayleigh-Benard convection, but arise from a
      distinct mechanism. Unlike the localized colloidal electroconvective patterns
      observed at lower biases, moreover, these system-spanning patterns form even
      without dispersed colloidal particles. Rather, they appear to result from an
      underlying electroconvective instability during electrolysis in the parallel
      plate geometry. This contrasts with recent theoretical results suggesting that
      simple electrolytes are linearly stable against electroconvection.

PMID- 17042632
TI  - Hydrogen bonding in the LaNi3BH3 hydride.
AB  - The electronic structure of the intermetallic LaNi3B as well as the novel hydride
      LaNi3BH3 have been theoretically investigated by means of quantum chemistry
      methods. We employed a mixed approach to investigate the electronic structure of
      these compounds: state-of-the-art energy band calculations and molecular cluster
      computations. We computed the energy bands and the total and partial density of
      states using both the linear-augmented plane waves and projector-augmented wave
      methods. In addition the electronic structure of three representative clusters of
      the local environment of Ni atoms was investigated by quantum chemistry ab initio
      molecular calculations. In this report, we discuss the chemical bonding and we
      investigated the H site occupancy energies and correlate this estimate with the
      occupancy fraction and metal-hydrogen distances experimentally observed.

PMID- 17042633
TI  - Complete wetting of curved microscopic channels.
AB  - We have measured the adsorption of argon films on arrays of microscopic nonlinear
      cusps and of semicircular channels. In the former case, we observe a distinct
      crossover from a planarlike to a geometry dependent growth behavior near liquid
      vapor bulk coexistence, characterized by a growth exponent chi equal to -0.96+/
      0.04 in very good agreement with the predictions of a recent scaling theory [C.
      Rascon and A. O. Parry, J. Chem. Phys. 112, 5175 (2000)]. The crossover location
      is also consistent with theory. Instead, on the concave channels we find a much
      steeper growth near saturation that may signal the formation of two menisci at
      both sides of the channel bottom.

PMID- 17042634
TI  - Dynamical motions of lipids and a finite size effect in simulations of bilayers.
AB  - Molecular dynamics (MD) simulations of dipalmitoylphosphatidylcholine bilayers
      composed of 72 and 288 lipids are used to examine system size dependence on
      dynamical properties associated with the particle mesh Ewald (PME) treatment of
      electrostatic interactions. The lateral diffusion constant Dl is 2.92 x 10(-7)
      and 0.95 x 10(-7) cm2/s for 72 and 288 lipids, respectively. This dramatic finite
      size effect originates from the correlation length of lipid diffusion, which
      extends to next-nearest neighbors in the 288 lipid system. Consequently,
      diffusional events in smaller systems can propagate across the boundaries of the
      periodic box. The internal dynamics of lipids calculated from the PME simulations
      are independent of the system size. Specifically, reorientational correlation
      functions for the slowly relaxing phosphorus-glycerol hydrogen, phosphorus
      nitrogen vectors, and more rapidly relaxing CH vectors in the aliphatic chains
      are equivalent for the 72 and 288 lipid simulations. A third MD simulation of a
      bilayer with 72 lipids using spherical force-shift electrostatic cutoffs resulted
      in interdigitated chains, thereby rendering this cutoff method inappropriate.

PMID- 17042635
TI  - Interfacial structures of methanol:water mixtures at a hydrophobic interface
      probed by sum-frequency vibrational spectroscopy.
AB  - Sum-frequency vibrational spectroscopy was used to study interfacial structure of
      methanol:water mixtures at an octyltrichlorosilane-covered hydrophobic surface.
      Methanol was found to adsorb preferentially than water at the interface with its
      methyl group tilted from the surface normal by approximately 35 degrees for all
      methanol concentrations. Redshift of the methanol symmetric stretch mode, gradual
      disappearance of the water dangling-OH mode, and blueshifts of the dangling and
      liquidlike bonded-OH modes were also observed as the methanol concentration
      increased. They could be understood from the change of the interfacial hydrogen
      bonding network associated with the change of surface composition.

PMID- 17042636
TI  - Molecular dynamics simulations of water droplets on polymer surfaces.
AB  - Molecular dynamics simulations were used to study the wetting of polymer surfaces
      with water. Contact angles of water droplets on crystalline and two amorphous
      polyethylene (PE) and poly(vinyl chloride) (PVC) surfaces were extracted from
      atomistic simulations. Crystalline surfaces were produced by duplicating the unit
      cell of an experimental crystal structure, and amorphous surfaces by pressing the
      bulk polymer step by step at elevated temperature between two repulsive grid
      surfaces to a target density. Different-sized water droplets on the crystalline
      PE surface revealed a slightly positive line tension on the order of 10(-12)-10(
      11) N, whereas droplets on crystalline PVC did not yield a definite line tension.
      Microscopic contact angles produced by the simple point charge (SPC) water model
      were mostly a few degrees smaller than those produced by the extended SPC model,
      which, as the model with lowest bulk energy, presents an upper boundary for
      contact angles. The macroscopic contact angle for the SPC model was 94 degrees on
      crystalline PVC and 113 degrees on crystalline PE. Amorphicity of the surface
      increased the water contact angle on PE but decreased it on PVC, for both water
      models. If the simulated contact angles on crystalline and amorphous surfaces are
      combined in proportion to the crystallinity of the polymer in question, simulated
      values in relatively good agreement with measured values are obtained.

PMID- 17042637
TI  - On the mechanism of anion desorption from DNA induced by low energy electrons.
AB  - Our knowledge of the mechanisms of radiation damage to DNA induced by secondary
      electrons is still very limited, mainly due to the large sizes of the system
      involved and the complexity of the interactions. To reduce the problem to its
      simplest form, we investigated specific electron interactions with one of the
      most simple model system of DNA, an oligonucleotide tetrameter compound of the
      four bases. We report anion desorption yields from a thin solid film of the
      oligonucleotide GCAT induced by the impact of 3-15 eV electrons. All observed
      anions (H-, O-, OH-, CN-, and OCN-) are produced by dissociative electron
      attachment to the molecule, which results in desorption peaks between 6 and 12
      eV. Above 14 eV nonresonant dipolar dissociation dominates the desorption yields.
      By comparing the shapes and relative intensities of the anion yield functions
      from GCAT physisorbed on a tantalum substrate with those obtained from isolated
      DNA basic subunits (i.e., bases, deoxyribose, and phosphate groups) from either
      the gas phase or condensed phase experiments, it is possible to obtain more
      details on the mechanisms involved in low energy electron damage to DNA,
      particularly on those producing single strand breaks.

PMID- 17042638
TI  - Nature of reactive O2 and slow CO2 evolution kinetics in CO oxidation by TiO2
      supported Au cluster.
AB  - Recent experiments on CO oxidation reaction using seven-atom Au clusters
      deposited on TiO2 surface correlate CO2 formation with oxygen associated with Au
      clusters. We perform first principles calculations using a seven-atom Au cluster
      supported on a reduced TiO2 surface to explore potential candidates for the form
      of reactive oxygen. These calculations suggest a thermodynamically favorable path
      for O2 diffusion along the surface Ti row, resulting in its dissociated state
      bound to Au cluster and TiO2 surface. CO can approach along the same path and
      react with the O2 so dissociated to form CO2. The origin of the slow kinetic
      evolution of products observed in experiments is also investigated and is
      attributed to the strong binding of CO2 simultaneously to the Au cluster and the
      surface.

PMID- 17042639
TI  - Collisions and reactions of gaseous propanol with molten NaOH/KOH.
AB  - Molecular beam scattering experiments are used to investigate collisions of a
      protic molecule, deuterated 1-propanol (PrOD), with an extremely basic solvent,
      the 5149 mol % NaOH/KOH eutectic mixture. This powerful deprotonating medium
      readily absorbs PrOD from the gas phase. Nearly all PrOD molecules that
      thermalize at the surface of the melt enter the liquid and dissolve for long
      times, most likely residing as PrO- after deprotonation by OH-. The PrO-
      solvation time is controlled by dissolved H2O, which reprotonates the anion and
      liberates D --> H exchanged PrOH. We find no evidence for decomposition of the
      alcohol; at the 463 K temperature of the experiments, the hydroxide solution
      appears to store propanol reversibly.

PMID- 17042640
TI  - Nonlinear optical approach to multiexciton relaxation dynamics in quantum dots.
AB  - Unlike the majority of molecular systems quantum dots can accommodate multiple
      excitations, which is a particularly important attribute for potential lasing
      applications. We demonstrate in this work the concept of using nth order
      nonlinear spectroscopies in the transient grating configuration as a means of
      selectively exciting (n-1)/2 excitons in a semiconductor and probing the
      subsequent relaxation dynamics. We report a direct observation of multiparticle
      dynamics on ultrashort time scales through comparison of third and fifth order
      experiments for CdSe colloidal quantum dots. Time constants associated with
      multiexciton recombination and depopulation dynamics are reported. Deviation from
      a Poisson model for the distribution of photoexcited excitons, biexcitons, and
      triexcitons is also discussed.

PMID- 17042641
TI  - Water properties inside nanoscopic hydrophobic pocket studied by computer
      simulations.
AB  - The structure and dynamics of water in the vicinity of the hemispherical
      hydrophobic pocket of 8 A radius were examined via molecular dynamics simulations
      in NVT ensemble. Density, hydrogen bonding properties, and residence times of
      water molecules were projected on two-dimensional planes providing a spatial
      description of water behavior. We found that the average water density is
      significantly depleted relative to bulk value. A detailed analysis of pocket
      occupancy revealed fluctuations between states of completely empty pocket and a
      pocket filled with a bulklike fluid, which seem to result from collective
      behavior of water molecules. Free energy differences accompanying these
      fluctuations are rather small, suggesting that the given pocket radius is close
      to the critical one for transition between gas and liquid phases in the
      considered system. We show that the situation is different in the case of a
      simple Lennard-Jones fluid. These results indicate that changing the surface
      curvature from flat to concave may lead to qualitative difference in water
      behavior in its vicinity. We think that our studies may also put some light on
      binding site desolvation process which is necessary to understand to make correct
      predictions of binding energies.

PMID- 17042642
TI  - Effect of surface tension and surface elasticity of a fluid-fluid interface on
      the motion of a particle immersed near the interface.
AB  - The motion of a particle immersed in a fluid near a fluid-fluid interface is
      studied on the basis of the linearized Navier-Stokes equations. The motion is
      influenced by surface tension, dilatational surface elasticity modulus, and
      surface shear modulus, as well as by gravity. The backflow at the location of the
      particle after a sudden impulse has some universal features that are the same as
      for a rigid wall with stick boundary conditions. At short times the flow depends
      only on the mass densities of the two fluids. The nature of the short-time flow
      is calculated from potential flow theory. At a somewhat later time the particle
      shows a pronounced rebound. The maximum value of the rebound and the time at
      which the maximum occurs depend on the elastic properties of the interface.

PMID- 17042643
TI  - Electronic structure of C60 on Au(887).
AB  - We present an analysis of the electronic structure of C60 adsorbed on a vicinal
      Au(111) surface at different fullerene coverages using photoemission, x-ray
      absorption, and scanning tunneling microscopy/spectroscopy (STS). STS provides a
      straightforward determination of the highest occupied molecular orbital (HOMO)
      and the lowest unoccupied molecular orbital (LUMO) levels with respect to the
      Fermi energy. At C60 coverages of 0.5 and 1 ML a 2.7 eV wide HOMO-LUMO gap is
      found. The near-edge x-ray absorption fine structure (NEXAFS) spectrum for the
      0.5 ML C60 nanomesh structure displays a significant intensity at the low energy
      side of the LUMO exciton peak, which is explained as due to absorption into HOMO
      LUMO gap states localized at individual C60 cluster edges. From 0.5 to 1 ML we
      observe a rigid shift of the HOMO-LUMO peaks in the STS spectra and an almost
      complete quenching of the gap states feature in NEXAFS.

PMID- 17042644
TI  - Quantum chemical study of electronic and structural properties of retinal and
      some aromatic analogs.
AB  - The electronic and structural properties of retinal and four analogs were studied
      using semiempirical, ab initio Hartree-Fock, and density functional theory
      methods with the aim to evaluate the effects caused by some structural
      modifications in the ring bound to the polyenic chain and compared with the all-E
      trans-retinal molecule. Therefore, some properties such as bond lengths, bond
      angles, atomic charges derived from electrostatic potential charges from
      electrostatic potential using grid based method as well as frontier orbitals of
      the polyenic chain were analyzed. Furthermore, the transition energies of the
      molecules were also calculated using the Zerner's intermediate neglect of
      differential overlap-spectroscopic, time-dependent Hartree-Fock, and time
      dependent density functional theory methods. The results indicate that in spite
      of the structural modifications of retinal derivatives in comparison with all-E
      trans-retinal, their properties seem similar. Thus, these molecules may behave
      similarly to all-E-trans-retinal and possibly be attempted in the search of novel
      molecular devices.

PMID- 17042645
TI  - Finite reservoir replica exchange to enhance canonical sampling in rugged energy
      surfaces.
AB  - A "finite reservoir" replica exchange method is presented to further enhance
      sampling upon the regular replica exchange method (REM) in a rugged energy
      surface. The present method can facilitate important sampling more efficiently by
      exchanging structures with configurations randomly selected from a finite-sized
      reservoir; this finite reservoir is pregenerated and updated by a mechanism of
      replica exchange with neighboring "temperature" simulations. In practice, this
      proposal revises exchange schedule in REM simulations in order to make productive
      exchange for conformational "tunneling" more frequent.

PMID- 17042646
TI  - Flexibility of phenylene oligomers revealed by single molecule spectroscopy.
AB  - The rigidity of a p-phenylene oligomer (p-terphenyl) has been investigated by
      single molecule confocal fluorescence microscopy. Two different rylene diimide
      dyes attached to the terminal positions of the oligomer allowed for wavelength
      selective excitation of the two chromophores. In combination with polarization
      modulation the spatial orientation of the transition dipoles of both end groups
      could be determined independently. We have analyzed 597 single molecules in two
      different polymer hosts, polymethylmethacrylate and Zeonex. On average we find a
      22 degrees deviation from the linear gas phase geometry (T = 0 K), indicating a
      rather high flexibility of the p-phenylene oligomer independent of the matrix. To
      substantiate our experimental results, we have performed quantum chemical
      calculations at the density functional theory level for the molecular geometry
      and the electronic excitations. Our findings are in agreement with former
      experiments on the persistence length of poly(p-phenylenes).

PMID- 17042647
TI  - Exact results for noise power spectra in linear biochemical reaction networks.
AB  - We present a simple method for determining the exact noise power spectra and
      related statistical properties for linear chemical reaction networks. The method
      is applied to reaction networks which are representative of biochemical processes
      such as gene expression. We find, for example, that a post-translational
      modification reaction can reduce the noise associated with gene expression. Our
      results also indicate how to coarse grain networks by the elimination of fast
      reactions. In this context we have discovered a breakdown of the sum rule which
      relates the noise power spectrum to the total noise. The breakdown can be
      quantified by a sum rule deficit, which is found to be universal, and can be
      attributed to the high-frequency noise in the fast reactions.

PMID- 17042648
TI  - Accurate estimation of the density of states from Monte Carlo transition
      probability data.
AB  - This study develops an efficient approach for calculating the density of states
      from energy transition probability matrices generated from extended sampling
      Monte Carlo simulations. Direct and iterative variants of the method are shown to
      achieve high accuracy when applied to the two-dimensional Ising model for which
      the density of states function can be determined exactly. They are also used to
      calculate the density of states of lattice protein and Lennard-Jones models which
      generate more complex nonzero matrix structures. Whereas the protein simulations
      test the method on a system exhibiting a rugged free energy landscape, the
      Lennard-Jones calculations highlight implementation details that arise in
      applications to continuous energy systems. Density of states results for these
      two systems agree with estimates from multiple histogram reweighting,
      demonstrating that the new method provides an alternative approach for computing
      the thermodynamic properties of complex systems.

PMID- 17042649
TI  - Testing one component plasma models on colloidal overcharging phenomena.
AB  - In this paper, the mechanisms of overcharging of a colloidal macroion in the
      presence of multivalent counterions are investigated by means of Monte Carlo
      simulations. This computational technique appears as a powerful tool for probing
      the validity of semianalytical models developed for this issue. In particular,
      the simulations performed are compared with the predictions of two different
      models based on the one component plasma (OCP) theory. Therein, the multivalent
      ionic atmosphere confined at the macroion surface is approximated by a two
      dimensional Wigner crystal. These kinds of models are largely used in the
      literature since (in some cases) they present quite simple equations to describe
      the electric double layer (EDL) of macroions with different geometries in the
      presence of much smaller (but still multivalent) ions. In this sense, charge
      inversion phenomena of membranes, polyelectrolytes, DNA molecules, etc., are
      straightforwardly predicted in terms of these expressions. Unfortunately,
      comparisons between these predictions and experimental results are scarce, mostly
      due to the difficulty to reproduce the experimental conditions in the laboratory.
      Accordingly, the goal of the present paper is to simulate EDLs under real
      conditions (in which overcharging phenomena are expected to happen) and use the
      results obtained in this way for comparing with those obtained from OCP models.

PMID- 17042650
TI  - Does equilibrium polymerization describe the dynamic heterogeneity of glass
      forming liquids?
AB  - A significant body of evidence indicates that particles with excessively high or
      low mobility relative to Brownian particles form in dynamic equilibrium in glass
      forming liquids. We examine whether these "dynamic heterogeneities" can be
      identified with a kind of equilibrium polymerization. This correspondence is
      first checked by demonstrating the presence of a striking resemblance between the
      temperature dependences of the configurational entropy s(c) in both the theory of
      equilibrium polymerization and the generalized entropy theory of glass formation
      in polymer melts. Moreover, the multiple characteristic temperatures of glass
      formation are also shown to have analogs in the thermodynamics of equilibrium
      polymerization, supporting the contention that both processes are varieties of
      rounded thermodynamic transitions. We also find that the average cluster mass (or
      degree of polymerization) varies in nearly inverse proportionality to s(c). This
      inverse relation accords with the basic hypothesis of Adam-Gibbs that the number
      of particles in the cooperatively rearranging regions (CRR) of glass-forming
      liquids scales inversely to s(c) of the fluid. Our identification of the CRR with
      equilibrium polymers is further supported by simulations for a variety of glass
      forming liquids that verify the existence of stringlike or polymeric clusters
      exhibiting collective particle motion. Moreover, these dynamical clusters have an
      exponential length distribution, and the average "string" length grows upon
      cooling according to the predictions of equilibrium polymerization theory. The
      observed scale of dynamic heterogeneity in glass-forming liquids is found to be
      consistent with this type of self-assembly process. Both experiments and
      simulations have revealed remarkable similarities between the dynamical
      properties of self-assembling and glass-forming liquids, suggesting that the
      development of a theory for the dynamics of self-assembling fluids will also
      enhance our understanding of relaxation in glass-forming liquids.

PMID- 17042654
TI  - Multislice computed tomographic angiography versus digital subtraction
      angiography in the follow-up of nitinol stents in the superficial femoral artery.
AB  - PURPOSE: To compare quantitative and qualitative parameters obtained from digital
      subtraction angiography (DSA) with multislice computed tomographic angiography
      (MSCTA) in the follow-up of superficial femoral artery (SFA) stents. METHODS:
      Thirteen patients who had SMART stents implanted in the SFA were examined
      systematically with DSA and MSCTA (16-row scanner) at 6 months. Quantitative
      analysis and morphological assessment were performed on DSA images by an
      independent core laboratory, while the MSCTA images were analyzed by 2
      radiologists in consensus. DSA measurements included stent length, minimal lumen
      diameter and reference diameter at mid stent and 5 mm either side of the stent,
      and percentage of stenosis. For MSCTA images, lumen area and the minimum,
      maximum, and mean diameters were also recorded. The images were analyzed
      qualitatively for diameter stenosis (<50%, 50% to 70%, 71% to 99%, and
      occlusion), bends, fractures, and calcifications. RESULTS: There were no
      statistical differences between lengths of stented segments, diameter
      measurements, or percentages of stenosis from DSA and MSCTA images. The Bland
      Altman method showed good agreement between the 2 methods of measurement. MSCTA
      detected in-stent proliferation with a diameter stenosis <50% in all 13 cases
      diagnosed on DSA (there was no stenosis >50%). There were no bends or stent
      fractures on either set of images. The agreement between DSA and MSCTA for the
      presence and grading of calcifications was moderate (kappa=0.5). CONCLUSION:
      MSCTA provided quantitative and qualitative data comparable with DSA in the
      analysis of SFA nitinol stents.

PMID- 17042655
TI  - Endovascular repair of dissecting thoracic aortic aneurysm in a patient with
      Turner syndrome.
AB  - PURPOSE: To report a rare case of dissecting thoracic aortic aneurysm in a young
      patient with Turner syndrome owing to complete or partial monosomy of the X
      chromosome. CASE REPORT: A 22-year-old patient with Turner syndrome presented
      with a 2-month history of voice loss and dysphagia. Multislice computed
      tomography (MSCT) disclosed a large (53x75-mm) aneurysm with focal dissection
      affecting the distal part of the aortic arch and the proximal descending aorta,
      partially involving the left subclavian artery. A TAG endoprosthesis was
      implanted without complications. MSCT scans at 3 and 6 months after the procedure
      showed good position and patency of the stent-graft, with total exclusion and
      shrinkage of the aneurysm. After 1 year of follow-up, she is doing well, without
      voice disturbances or dysphagia. CONCLUSION: Although cardiovascular
      malformations are common in patients with Turner syndrome, dissecting thoracic
      aortic aneurysm is unusual. Stent-graft repair would appear to be feasible in
      this situation, but long-term implantation in young patients has not been
      explored.

PMID- 17042656
TI  - Combined endovascular and surgical treatment of infected carotid-carotid bypass
      graft.
AB  - PURPOSE: To present a complex case involving an infected carotid-carotid bypass
      graft that was successfully treated with a stent-graft and subsequent surgical
      removal of the infected graft. CASE REPORT: A 75-year-old woman presented with
      persistent purulent drainage of an infected and exposed carotid-carotid
      prosthetic bypass graft. Wound cultures revealed methicillin-resistant
      Staphylococcus aureus. She was treated with appropriate intravenous antibiotic
      therapy without improvement in wound drainage. Because of her comorbid
      conditions, a decision was made to pursue endovascular revascularization of her
      left and right common carotid arteries (CCA), with subsequent surgical removal of
      the infected prosthetic graft. The patient underwent balloon angioplasty; a 7x18
      mm Omnilink stent was deployed in the innominate artery and a 7x18-mm Herculink
      stent in the ostial left CCA. During the same procedure, the carotid-carotid
      bypass graft was excluded with deployment of an 8x50-mm Viabahn stent-graft in
      the right CCA. Several days later, the infected and now thrombosed carotid
      carotid bypass graft was surgically removed, and an area of adjacent muscle was
      used to patch the previously excluded connection of the bypass from the right
      CCA. A saphenous vein patch was used to repair the defect in the left CCA. Her
      postoperative course was uneventful. At 1 year, the clinical and duplex
      examinations revealed satisfactory wound healing and patent left and right CCAs.
      CONCLUSION: This case indicates that a combined endovascular and surgical
      approach may be a safe and effective option in the treatment of carotid-carotid
      bypass graft infection.

PMID- 17042657
TI  - Indication for carotid endarterectomy versus carotid stenting for the prevention
      of brain embolization from carotid artery plaques: in search of consensus.

PMID- 17042658
TI  - Midterm outcomes from the TALON Registry: treating peripherals with SilverHawk:
      outcomes collection.
AB  - PURPOSE: To determine midterm clinical outcomes among patients with lower
      extremity peripheral arterial disease who underwent revascularization with
      catheter-based plaque excision (PE). METHODS: Between August 2003 and February
      2005, 19 institutions participating in the observational, nonrandomized,
      multicenter TALON registry enrolled 601 consecutive patients (353 men; mean age
      70+/-11, range 36-98) with 1258 symptomatic lower extremity atherosclerotic
      lesions (748 limbs) treated by plaque excision with the SilverHawk catheter.
      Approximately 50% of the patients had diabetes, and nearly one third of the
      procedures were indicated for Rutherford ischemia category > or =4. Mean lesion
      lengths above and below the knee, respectively, were 62.5+/-68.5 mm
      (interquartile range [IQR], 20.0-80.0) and 33.4+/-42.7 mm (IQR 15.0-37.5). The
      primary endpoints of the study were target lesion revascularization (TLR) at 6
      and 12 months. RESULTS: The device achieved < or =50% residual diameter stenosis
      in 94.7% of lesions; procedural success was 97.6%. Nearly half (41.9%) of the
      procedures involved PE of > or =2 lesions. Nearly three quarters (73.3%) of the
      lesions did not require adjunctive therapy, and stent placement following PE
      occurred in only 6.3% of lesions. The 6- and 12-month rates of survival free of
      TLR were 90% and 80%, respectively. Rates of TLR were similar among patients with
      diabetes (11%) and without diabetes (9%). In the multivariate analysis,
      significant predictors of TLR at 6 months were a history of MI or coronary
      revascularization (HR 5.49, 95% CI 1.87 to 16.10, p=0.0008), multiple (> or =2)
      lesions (HR 1.37, 95% CI 1.11 to 1.70, p=0.0019), and increasing Rutherford
      category (HR 1.84, 95% CI 1.28 to 2.65, p=0.0003). Lesion length >50 mm was
      associated with a 2.9-fold increased risk for TLR (HR 2.88, 95% CI 1.18 to 7.01,
      p=0.012); lesion length >100 mm was associated with a 3.3-fold increase in TLR
      (HR 3.32, 95% CI 1.15 to 9.56, p=0.016). CONCLUSION: In patients undergoing
      revascularization for lower extremity atherosclerotic disease, catheter-based PE
      achieves favorable procedural success and avoids the need for repeat
      revascularization at midterm follow-up. These findings support PE as a primary
      endovascular therapy for patients undergoing lower extremity arterial
      revascularization.

PMID- 17042659
TI  - Paclitaxel delivered to adventitia attenuates neointima formation without
      compromising re-endothelialization after angioplasty in a porcine restenosis
      model.
AB  - PURPOSE: To investigate the effect of paclitaxel delivered into the adventitia of
      pig femoral arteries on neointima formation and hyperplasia as well as re
      endothelialization. METHODS: Paclitaxel or vehicle was delivered into the
      adventitia of pig femoral arteries using a needle injection catheter following
      balloon overstretch. Arteries were then serially examined by angiography, Evan's
      blue staining, morphometry, and immunohistochemistry for up to 12 weeks. RESULTS:
      Local adventitial delivery of paclitaxel significantly attenuated neointima
      formation. The area of neointima (0.41+/-0.17 versus 2.75+/-0.81 mm(2), p<0.01),
      the ratio of intima to media (0.12+/-0.05 versus 0.86+/-0.35, p<0.05), and the
      degree of stenosis (12.80%+/-3.13% versus 47.06%+/-7.25%, p<0.01) were
      significantly lower in the paclitaxel-treated group compared to controls.
      Furthermore, cell proliferation was significantly diminished following
      adventitial delivery of paclitaxel from day 3 to 21 compared to controls.
      Complete re-endothelialization was observed 3 weeks after intervention in both
      groups of arteries treated with paclitaxel or vehicle alone. CONCLUSION:
      Paclitaxel delivered into the adventitia of pig femoral arteries effectively
      attenuates neointima formation after angioplasty without compromising re
      endothelialization. Adventitial drug delivery may therefore be an alternative to
      drug-eluting stents for the prevention of restenosis.

PMID- 17042660
TI  - Sirolimus-eluting stenting of the external carotid artery for the treatment of
      ocular ischemia.
AB  - PURPOSE: To present a patient in whom severe external carotid artery (ECA)
      stenosis causing ocular ischemia was treated with a drug-eluting stent. CASE
      REPORT: A 55-year-old woman with severe, diffuse atherosclerosis presented with
      impaired left ocular perfusion and amaurosis fugax. Duplex ultrasonography and
      angiography documented bilateral occlusion at the origin of the internal carotid
      arteries, bilateral subtotal ECA stenoses, and subtotal distal left common
      carotid artery (CCA) restenosis following endarterectomy. Percutaneous
      revascularization of the left ECA and CCA stenoses was performed using a short
      coronary balloon-expandable sirolimus-eluting stent and a self-expanding nitinol
      stent, respectively. The procedure was uneventful, and the ocular symptoms
      resolved. At 6 months, the patient remained asymptomatic, with angiographically
      patent stents. CONCLUSION: Drug-eluting stenting may be a novel option to treat
      symptomatic ECA stenosis.

PMID- 17042661
TI  - Percutaneous laser-facilitated thrombectomy: an innovative, easily applied, and
      effective therapeutic option for recanalization of acute and subacute thrombotic
      hemodialysis shunt occlusions.
AB  - PURPOSE: To report our experience with excimer laser-facilitated recanalization
      of acute and subacute thrombotic occlusions of hemodialysis shunts. METHODS:
      Twenty-one patients (16 women; mean age 54+/-19 years, range 31-76) presented
      with acute and subacute thrombotic occlusions of their hemodialysis shunts (4
      Cimino, 17 prosthetic; 18 forearm, 3 upper arm); mean occlusion time was 4.1+/-3
      days (range 1-14), and the thrombotic occlusion measured a mean 17.4+/-9 cm
      (range 5-27). Fresh thrombus was observed in addition to the total shunt
      occlusion in all cases. All patients were treated initially with a pulsed
      ultraviolet (308-nm) excimer laser. Eighteen (85.7%) patients received adjunctive
      local thrombolysis for treatment of residual thrombus. Nineteen (90.5%) patients
      underwent angioplasty of the underlying anastomotic stenosis. RESULTS: The
      angiographic occlusion was reduced from 100% to 63%+/-28% after laser treatment
      and to 36%+/-18% after 1 hour of thrombolytic therapy (20 mg tissue plasminogen
      activator). TIMI flow increased significantly from grade 0 to 2.7+/-0.5 following
      laser ablation (p<0.001) and to 3.0+/-0.2 upon completion of the angioplasty
      procedure (p>0.001 versus baseline). The immediate procedural success was 95.2%
      (20/21). Detectable thrombotic embolization and laser-related complications were
      not observed in any case. Primary patency was 85%; 3 patients had abnormal
      Doppler flow within 6 weeks and underwent reintervention (secondary patency
      100%). All successfully treated shunts were usable for further dialysis at the 6
      week follow-up. CONCLUSION: Percutaneous excimer laser-facilitated thrombus
      vaporization is safe and effective for recanalization of acute and subacute
      thrombotic occlusions of hemodialysis shunts.

PMID- 17042662
TI  - Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular
      AAA repair? A randomized controlled pilot study.
AB  - PURPOSE: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast
      nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as
      evidenced by changes in markers of renal function. METHODS: Twenty consecutive
      men (mean age 72 years, range 65-79) undergoing EVAR were randomized to receive
      standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg
      BID orally, 4 doses). Venous blood and urine were collected prior to the
      procedure and for 5 postoperative days and analyzed blindly for serum creatinine,
      urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR).
      RESULTS: There were no significant differences in baseline demographics between
      the groups. No patient developed acute renal failure. In both groups, urinary RBP
      rose significantly from baseline (median 15 microg/mmol to peak 699 microg/mmol
      in controls versus 17 to 648 microg/mmol in the treatment group, p<0.003). There
      were similar significant rises in ACR (p<0.02). There was, however, no
      significant difference in the postoperative RBP or ACR between the groups at any
      time point. CONCLUSION: EVAR causes significant acute renal injury in most
      patients. This was not attenuated by N-acetylcysteine. The causes of renal injury
      are probably multifactorial, the long-term clinical significance of which is
      unclear.

PMID- 17042663
TI  - Intentional coverage of a main renal artery during endovascular juxtarenal aortic
      aneurysm repair in symptomatic high-risk patients.
AB  - PURPOSE: To describe the efficacy and morbidity of intentionally covering a main
      renal artery during symptomatic juxtarenal endovascular aneurysm repair (EVAR).
      CASE REPORTS: Two patients with symptomatic juxtarenal abdominal aortic aneurysm
      (AAA) were felt to be at prohibitive risk for open repair. Each underwent EVAR
      with intentional coverage of 1 main renal artery to achieve adequate proximal
      hemostatic seal. One patient died at 24 months; the second is symptom-free at 10
      months. Both aneurysms initially decreased in diameter. Both patients had
      increased serum creatinine and required increased therapy for hypertension, but
      neither required hemodialysis. Renal volume decreased 48.7% and 68.0%,
      respectively. CONCLUSION: Intentional coverage of a main renal artery during EVAR
      for a symptomatic juxtarenal aneurysm resulted in effective short-term AAA repair
      with no need for dialysis. Despite the increased requirement for antihypertensive
      medications and the observed decline in renal function, this technique provides
      an option for treatment of this difficult patient subset.

PMID- 17042664
TI  - EndoFit stent-graft repair of isolated common iliac artery aneurysms with short
      necks.
AB  - PURPOSE: To evaluate the feasibility and efficacy of repairing isolated iliac
      artery aneurysms with short proximal necks (<10 mm) by implanting the EndoFit
      stent-graft. METHODS: Seven patients (6 men; median age 73 years, range 70-78)
      were diagnosed with an isolated common iliac artery (CIA) aneurysm that featured
      a short proximal landing zone, complicating endovascular treatment. The median
      aneurysm diameter was 4.4 cm (range 3.5-7.0), and the median proximal neck length
      was 7 mm (range 5-9).The aneurysms were treated using the EndoFit stent-graft,
      which can be deployed in a short proximal landing zone. The modified technique
      involves the deployment of the graft directly above the aneurysm sac without
      obstructing the contralateral iliac axis, thus affixing the bare proximal stent
      in the terminal aorta. Follow-up was performed by clinical evaluation and
      computed tomography at 1, 6, and 12 months postoperatively. RESULTS: The EndoFit
      stent-graft was successfully deployed in all cases, with complete aneurysm
      exclusion. In 1 case, the deployment of a second cuff was necessary to secure
      complete aneurysm exclusion. The median follow-up was 18 months, during which no
      deaths occurred, and no endoleak or stent-graft migration was observed. Endograft
      thrombosis occurred in 1 case due to graft angulation caused by external iliac
      artery stenosis and kinking. None of the aneurysms has ruptured, and there have
      been no serious complications. CONCLUSION: Direct endoluminal repair of isolated
      CIA aneurysms with short proximal necks is feasible using this technique.
      Efficacy and long-term results are to be confirmed by larger scale series over a
      long time period.

PMID- 17042665
TI  - Factors influencing the need for target vessel revascularization after renal
      artery stenting.
AB  - PURPOSE: To provide additional insight into factors that may be associated with
      the need for target vessel revascularization (TVR) following de novo renal artery
      stenting during long-term follow-up. METHODS: A retrospective chart and database
      review was conducted to analyze the progress of all patients with de novo
      symptomatic renal artery stenosis who underwent stent-supported angioplasty under
      the auspices of the Single Operator, Single Center, Renal Stent Retrospective
      Study (SOCRATES). The records review identified 782 patients who were enrolled in
      the study between 1993 and 2004; after excluding 34 (4.5%) patients (lost to
      follow-up or inadequate data), 748 consecutive patients (412 women; mean age
      70.7+/-9.7 years, range 37-92) were suitable for longitudinal analysis. The need
      for TVR was based on strict clinical criteria (> or =20% rise in serum
      creatinine, worsening hypertension, and/or recurrent flash pulmonary edema), and
      all patients underwent multidisciplinary evaluation before stenting and during
      follow-up. RESULTS: Follow-up spanned a mean 45.8+/-26.5 months. TVR was needed
      in 88 (10.03%) of 877 arteries and was best predicted by patient age < or =67
      years (OR 2.91, p=0.0001), stent diameter < or =5.0 mm (OR 2.31, p=0.001),
      solitary functioning kidney (OR 2.01, p=0.048), history of lower extremity
      peripheral artery disease (OR 1.87, p=0.008), and antecedent history of stroke
      (OR 1.73, p=0.026). CONCLUSION: Renal artery stenting appears to be durable, with
      only 10% of stented arteries requiring TVR during clinically-based long-term
      follow-up. Arteries with a final stent diameter < or =5.0 mm were more than twice
      as likely to need TVR, as were patients with a solitary kidney. The authors
      acknowledge that clinical recurrence is not a surrogate for ultrasound
      surveillance after renal artery stenting, so prospective controlled trials will
      be needed to determine risk factors for restenosis.

PMID- 17042666
TI  - Evolution and future of preclinical testing for endovascular grafts.
AB  - The preclinical testing of endovascular grafts has evolved significantly since
      the creation and early testing of these devices; however, there are continued
      limitations in using preclinical testing to predict clinical performance. Early
      testing was conducted in the absence of standards and guidance specific to
      endovascular grafts, and references available for vascular grafts and stents did
      not adequately account for the complexity of endovascular graft systems. Failure
      of early-generation devices suggested that the testing being conducted was
      inadequate and that there was a lack of understanding of the in vivo environment.
      These concerns led to several efforts to improve preclinical testing. The Food
      and Drug Administration (FDA) sponsored a workshop to discuss the limitations
      inherent in testing of endovascular grafts, and an ISO standard for endovascular
      grafts was developed. Publication of the standard in 2003 succeeded in
      standardizing testing and reporting across device manufacturers; however, several
      clinical failure modes, such as migration and stent fractures, continued to be
      unpredicted by current preclinical testing. This, coupled with knowledge gained
      from additional clinical experience, led the FDA to hold a second workshop to
      discuss the benefits and limitations of current testing and propose future
      testing that may better predict device performance. This workshop was successful
      in accurately describing past testing, determining what has been learned,
      identifying issues that have not been adequately addressed, proposing
      modifications to address these limitations, and discussing how the proposed
      modifications should be implemented. While significant progress has been made in
      endovascular graft testing, continued collaboration among industry, academia,
      regulators, and clinicians will provide continued improvement in the
      predictability of device performance.

PMID- 17042667
TI  - Late perforation of a thoracic aortic dacron graft by a metallic stent-graft
      component.
AB  - PURPOSE: To describe a case involving perforation of a previously placed aortic
      Dacron graft by the uncovered proximal stent of a thoracic stent-graft. CASE
      REPORT: A 76-year-old man with a surgically treated type A dissection presented
      with residual type B dissection. Thoracic stent-grafting of the entry site was
      performed successfully. After 2 years, the patient was admitted for evaluation of
      a non-pulsating parasternal mass. Computed tomography showed a large, hypodense
      liquid-like mass affecting the mediastinum up to the subcutaneous tissue. A false
      aneurysm at the proximal end of the stent-graft was observed arising from an
      aortic perforation by the uncovered stent. One week later, the mass had almost
      completely resolved, and the patient has been scheduled for close surveillance.
      CONCLUSION: This case illustrated the importance of thoroughly examining the long
      term durability and compatibility of prosthetic materials.

PMID- 17042668
TI  - Influence of infrarenal neck length on outcome of endovascular abdominal aortic
      aneurysm repair.
AB  - PURPOSE: To evaluate the influence of the infrarenal neck length on clinical
      outcome after endovascular abdominal aortic aneurysm repair (EVAR). METHODS: Data
      were analyzed from 3499 patients enrolled in the EUROSTAR registry between
      January 1999 and April 2005 who underwent EVAR with a Talent or Zenith endograft
      and had detailed morphological data recorded. The study cohort was divided into 3
      groups according to infrarenal neck length: >15 mm (reference group A, n=2822),
      11 to 15 mm (group B, n=485), and < or =10 mm (group C, n=192). Uni- and
      multivariate analyses were performed to evaluate differences in clinical outcomes
      among the study groups. RESULTS: After correction for confounders, proximal type
      I endoleak within 30 days occurred in 10.9% of group C compared to 2.6% of group
      A (OR 4.46, 95% CI 2.61 to 7.61). Within 48 months of follow-up (median 12
      months), the incidence of proximal endoleaks was higher in groups B (9.6%; HR
      1.98, 95% CI 1.16 to 3.38) and C (11.3%; HR 2.132, 95% CI 1.17 to 4.60) compared
      to group A (3.4%). CONCLUSION: Our study indicates that endovascular treatment of
      abdominal aortic aneurysms with infrarenal neck length <15 mm is associated with
      significantly increased risk of short- and midterm proximal endoleaks after EVAR.
      The greater risk of proximal endoleaks should be weighed against the risks of
      alternative treatment modalities.

PMID- 17042669
TI  - Iliac anastomotic stenting with a sirolimus-eluting biodegradable poly-L-lactide
      stent: a preliminary study after 6 weeks.
AB  - PURPOSE: To assess technical feasibility and biocompatibility of a new
      biodegradable sirolimus-eluting poly-L-lactide (PLLA) vascular anastomotic stent.
      METHODS: A polytetrafluoroethylene bifurcated graft was implanted in 9 pigs
      through a midline abdominal incision. After transverse graft limb incision, 6
      unloaded PLLAs, 6 sirolimus-loaded PLLAs, and 6 unloaded stainless steel (316L)
      stents were randomly implanted at both iliac anastomotic sites. Stents were
      deployed with a 6-mm balloon under direct vision without the use of angiography.
      Prior to sacrifice after 6 weeks, contrast-enhanced computed tomography (CT) was
      performed to determine patency of the target vessels. Stented segments were
      surgically explanted and processed for histology to measure the mean luminal
      diameter and intimal thickness and to assign vascular injury and inflammation
      scores. RESULTS: No animals were lost during the study period. All stented graft
      limbs were patent on CT and histology. At the anastomotic sites and iliac
      arteries, the mean luminal diameter of SIR-PLLA stents (4.11+/-0.15 and 4.08+/
      0.13 mm, respectively) were comparable to metal stents (4.23+/-0.35 and 4.21+/
      0.26 mm, respectively), but significantly higher compared to unloaded PLLA stents
      [3.32+/-0.56 mm (p<0.001) and 3.29+/-0.39 mm (p=0.013), respectively]. At the
      iliac arteries, the mean intimal thickness was significantly lower with SIR-PLLA
      stents (0.09+/-0.02 mm) compared to unloaded PLLA stents (0.31+/-0.15 mm,
      p<0.001) and metal stents (0.19+/-0.04 mm, p=0.004). Vascular injury scores
      demonstrated only mild vascular trauma for all stents (SIR-PLLA: 0.42+/-0.63,
      PLLA: 0.51+/-0.62, metal: 0.50+/-0.62). Only mild inflammatory reaction was noted
      around SIR-PLLA stent struts (1.14+/-0.46), which was comparable to metal stents
      (1.27+/-0.45) but significantly lower than PLLA stents (1.79+/-0.56, p<0.001).
      CONCLUSION: SIR-PLLA stents showed comparable luminal diameter compared to metal
      stents, so incorporating sirolimus could reduce the inflammatory and neointimal
      response to PLLA stents. These findings need to be assessed with longer follow-up
      to confirm maintenance of efficacy.

PMID- 17042671
TI  - Regarding "Distal embolism during percutaneous revascularization of infra-aortic
      arterial occlusive disease: an underestimated phenomenon".

PMID- 17042673
TI  - An assessment of statin safety.
AB  - Recently, statin safety and potential drug interactions have received close
      attention in the consumer and medical press. In particular, rosuvastatin, the
      most recent statin introduced into the US market, has been the object of much
      speculation. Many of these reports have lost sight of the proven efficacy of
      statins in coronary disease prevention at a time when coronary heart disease is
      the number one killer of adults, and have failed to frame the potential drug
      toxicity in the context of this benefit. Summarized here are the conclusions of
      the National Lipid Association's Statin Safety Assessment Task Force, which
      reviewed extensive new drug application (NDA) and postmarketing data for all the
      currently marketed statins regarding their effect on the liver, muscle, renal,
      and neurologic systems. The task force found that, overall, hepatic, renal, or
      neurologic function does not appear to be compromised by statin use. They do not
      recommend routine monitoring of these systems but do recommend ongoing
      surveillance of symptomatic patients. With respect to muscle toxicity, the task
      force's Muscle Expert Panel concluded that the incidence of myopathy and
      rhabdomyolysis is low and appears to be dose-related, rather than associated with
      the degree of low-density lipoprotein cholesterol lowering and also appears to be
      related to the individual statin used. For example, from the rosuvastatin NDA
      database and additional postmarketing data, the overall incidence of myopathy was
      found to be lower than that observed with other statins. Administrative claims
      data of hospitalization rates for adverse events in statin patients confirm the
      task force conclusion that, overall, statins are safe and well tolerated when
      used as monotherapy.

PMID- 17042674
TI  - Rising to the challenge of treating high-risk patients.
AB  - Guidelines from the National Cholesterol Education Program (NCEP) Adult Treatment
      Panel III (ATP III) focus the need for the most intensive efforts to lower low
      density lipoprotein cholesterol (LDL-C) in the patients at greatest risk of a
      major future clinical coronary heart disease event. Major clinical trials, such
      as Pravastatin or Atorvastatin Evaluation and Infection Therapy and the Heart
      Protection Study, demonstrated the value of lowering LDL-C levels in high-risk
      patients to well below the ATP III target of <100 mg/dL. In 2004, the NCEP
      writing group suggested that a more aggressive LDL-C goal of <70 mg/dL is an
      option when treating high-risk patients, particularly those with the presence of
      established cardiovascular disease plus major multiple risk factors (especially
      diabetes), severe and poorly controlled risk factors (ie, cigarette smoking),
      multiple criteria of the metabolic syndrome, or an acute coronary syndrome. With
      stricter targets, high-risk patients are less likely to achieve their cholesterol
      goals than lower risk patients. Recent large trials comparing rosuvastatin with
      other statin monotherapies have shown a greater LDL-C reduction and better
      attainment of goals with rosuvastatin. In addition, the MERCURY [Measuring
      Effective Reductions in Cholesterol Using Rosuvastatin Therapy] trials
      demonstrate that switching to rosuvastatin significantly increased the percentage
      of patients who achieved their ATP III LDL-C targets.

PMID- 17042675
TI  - Cost efficiency and formulary considerations for statin therapy.
AB  - Extensive epidemiologic evidence and reports issued by the National Cholesterol
      Education Program have repeatedly identified low-density lipoprotein cholesterol
      (LDL-C) as the primary target in reducing the primary and secondary risk of
      coronary events. With recent evidence supporting a more aggressive approach using
      higher potency statins, and a lower threshold for initiating drug therapy for
      high-risk patients, providers and administrators in managed care are charged with
      finding the most effective and cost-effective means of attaining these goals.
      Changes in the market, such as newer high-potency statins and statin combinations
      available at lower cost and expiration of patents on widely accepted brand drugs,
      have provided practitioners with the ability to reduce LDL-C at lower costs than
      ever. The cost-efficiency analysis presented here finds that, for low-to-moderate
      reduction (<40%), generic lovastatin and simvastatin provide the lowest cost per
      1% LDL-C reduction. Similarly, for reduction greater than 40%, branded
      rosuvastatin and ezetimibe/simvastatin have the lowest cost per 1% reduction.

PMID- 17042676
TI  - Iodine nutrition requirements during pregnancy.

PMID- 17042677
TI  - Iodine supplementation for pregnancy and lactation-United States and Canada:
      recommendations of the American Thyroid Association.
AB  - The fetus is totally dependent in early pregnancy on maternal thyroxine for
      normal brain development. Adequate maternal dietary intake of iodine during
      pregnancy is essential for maternal thyroxine production and later for thyroid
      function in the fetus. If iodine insufficiency leads to inadequate production of
      thyroid hormones and hypothyroidism during pregnancy, then irreversible fetal
      brain damage can result. In the United States, the median urinary iodine (UI) was
      168 microg/L in 2001-2002, well within the range of normal established by the
      World Health Organization (WHO), but whereas the UI of pregnant women (173
      microg/L; 95% CI 75-229 microg/L) was within the range recommended by WHO (150
      249 microg/L), the lower 95% CI was less than 150 microg/L. Therefore, until
      additional physiologic data are available to make a better judgment, the American
      Thyroid Association recommends that women receive 150 microg iodine supplements
      daily during pregnancy and lactation and that all prenatal vitamin/mineral
      preparations contain 150 microg of iodine.

PMID- 17042679
TI  - Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro
      modulation by rosiglitazone and dexamethasone.
AB  - BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of
      peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine
      bias. However, the immunomodulatory factors involved in regulating this response
      have so far received scant attention. In this study, we examine the effects of
      the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon
      (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+)
      and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects
      (n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in
      vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or
      absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0
      microM, and 100 microM). Cytokine expression was determined by flow cytometry.
      RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls
      (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A
      dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and
      rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both
      dexamethasone and rosiglitazone was greater in control subjects than in patients
      (p < 0.05). There was no significant difference in IL-4 expression between
      patients and control groups and its expression remained unaffected by either
      compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT
      patients express a type 1 cytokine bias that is significantly more resistant to
      in vitro modulation by rosiglitazone and dexamethasone. Further studies are
      needed to clarify if this resistance plays a role in the pathogenesis of
      autoimmune thyroid disease (AITD).

PMID- 17042680
TI  - Effect of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary
      axis in rats.
AB  - OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing
      countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism.
      The study aim was to investigate the effects of concurrent vitamin A and iodine
      deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n =
      56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin
      A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine
      (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones
      (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA
      expression levels, and thyroid weights were determined at the end of the
      depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR
      concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001),
      indicating moderate VA deficiency. Comparing the VAD and control groups, there
      were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid
      hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and
      thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in
      the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and
      thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001)
      in the VAD + ID group. There were no significant differences in TT3 or FT3
      concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable
      effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe
      primary hypothyroidism than ID alone.

PMID- 17042681
TI  - Study of serum antibodies against three eye muscle antigens and the connective
      tissue antigen collagen XIII in patients with Graves' disease with and without
      ophthalmopathy: correlation with clinical features.
AB  - OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in
      the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO).
      Our aim was to determine the prevalence and level of antibodies against three
      candidate eye muscle antigens and the orbital fibroblast membrane antigen
      collagen XIII, in well-characterized patient groups. STUDY DESIGN AND PATIENTS:
      The study cohort consisted of patients with Graves' hyperthyroidism with and
      without ophthalmopathy, controls patients with other thyroid or other autoimmune
      disorders and healthy subjects. The presence of eye muscle antibodies was
      determined using an optimized and standardized enzyme-linked immunosorbent assay.
      We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the
      mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment
      of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa
      calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that
      is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle
      antibody levels were correlated with clinical diagnosis and presence or not of
      ophthalmopathy. RESULTS: Prevalences of positive antibody tests to calsequestrin
      (75.0%) and collagen XIII (43.8%) were significantly greater in Graves' disease
      (GD) patients with ophthalmopathy than in healthy subjects, whereas modest
      significance was demonstrated with antibodies against Fp, but not G2s.
      Significantly greater serum levels of antibodies against calsequestrin, G2s, and
      collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared
      to control patients without eye disease and healthy subjects. CONCLUSIONS:
      Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas
      antibodies against G2s, and to a lesser extent Fp, are also markers of
      ophthalmopathy, but less reliable. These results are unique in that it is the
      first time the significance of a panel of three candidate eye muscle antibodies
      and a connective tissue antibody have been evaluated in the same patients with
      ophthalmopathy.

PMID- 17042682
TI  - Fine-needle aspiration biopsy of thyroid lesions processed by thin-layer
      cytology: one-year institutional experience with histologic correlation.
AB  - Fine-needle aspiration biopsy (FNAB) is important for classifying thyroid
      lesions. Thin-layer cytology (TLC) has been adopted in thyroid cytology with
      encouraging results and its efficacy in diagnosing nodular lesions in a 1-year
      period was evaluated. All 2006 thyroid FNAB processed by TLC only in the year
      2004 were examined. The 2002 and 2003 series, processed both by TLC and
      conventional smears (CS), were used as controls. All FNAB were classified
      according to previously published morphologic criteria. Surgery was performed on
      311 cases: all 98 benign and 30 malignant lesions were histologically confirmed.
      The inadequate diagnoses resulted 11.3% in 2004, 13.3% in 2003, and 18.2% in
      2002. The indeterminate diagnosis rate was 16.9% in 2004, 20.7% in 2003, and
      24.8% in 2002. Sensitivity, specificity, and diagnostic accuracy values ranged
      from 80% to 100%. TLC is useful in reducing inadequate and indeterminate cases
      without decreasing the preoperative diagnostic accuracy. Ancillary techniques can
      be successfully applied to the stored material.

PMID- 17042683
TI  - Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid.
AB  - BACKGROUND: Recent developments in ultrasonography (US) and the prevalence of
      ultrasound-guided fine needle aspiration biopsy (US-FNAB) has enabled physicians
      to detect and diagnosis thyroid diseases, including thyroid malignant lymphoma,
      much more easily. METHODS: We describe our diagnostic strategy for malignant
      lymphoma on US screening. We screened possible malignant lymphoma patients by US
      characteristics such as enhanced posterior echoes. RESULTS: Among 170 patients
      suspected of malignant lymphoma between 2000 and 2004, 74 (43.5%) were also
      diagnosed as having or suspected of lymphoma by US-FNAB. Five patients dropped
      out, and 67 of 69 patients who underwent surgical examination were pathologically
      diagnosed as having lymphoma. Finally, 79 (47.9%) of 165 US-suspected patients
      were confirmed as having lymphoma. Only 21.5% of lymphoma patients complained of
      rapidly growing goiter. CONCLUSION: US screening for goiters contributes markedly
      to diagnosis of lymphoma at an early phase, facilitating early initiation of
      therapy.

PMID- 17042684
TI  - Thyroid color flow Doppler sonography: an adjunctive tool for differentiating
      patients with inappropriate thyrotropin (TSH) secretion due to TSH-secreting
      pituitary adenoma or resistance to thyroid hormone.
AB  - BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenoma (TSHoma) and resistance
      to thyroid hormone (RTH) are two forms of inappropriate TSH secretion. Thyroid
      blood flow is largely TSH dependent. OBJECTIVE: To assess whether thyroid blood
      flow may help to differentiate TSHoma and RTH. DESIGN: Intrathyroidal color flow
      Doppler sonography (CFDS) pattern and peak systolic velocity (PSV) were assessed
      at baseline and during T(3) suppression test on eight consecutive patients with
      TSHoma and 10 with RTH. MAIN OUTCOME: All controls had CFDS pattern 0. Three RTH
      patients had pattern I and seven had pattern II. Two TSHoma patients had pattern
      I, five had pattern II, and one had pattern III. PSV at baseline was 3.8 +/- 1.3
      cm/s in controls, 8.8 +/- 2.5 cm/s in RTH, 11.1 +/- 2.7 cm/s in TSHoma (p <
      0.0003 vs. controls, p = 0.087 RTH vs. TSHoma). After T3 suppression test, PSV
      values were lower in RTH than in TSHoma (4.6 +/- 1.8 vs. 7.7 +/- 2.6 cm/s, p =
      0.008). PSV values and CFDS pattern normalized in nine and eight RTH patients,
      respectively, after T(3) suppression test; conversely, only one TSHoma patient
      had a normalization of PSV values, and none had a normalization of CFDS pattern
      (p < 0.003 vs. RTH). CONCLUSIONS: Both RTH and TSHoma have increased CFDS pattern
      and PSV values; however, after T(3) both parameters normalized in most patients
      with RTH but not in those with TSHoma. Accordingly, CFDS pattern and PSV are
      adjunctive tools to differentiate these two forms of inappropriate TSH secretion.

PMID- 17042685
TI  - Scanning electron microscopy of thyroid cells under fully hydrated conditions--a
      novel technique for a seasoned procedure: a brief observation.
AB  - Technical information for handling fine-needle aspiration samples from thyroid
      lesions for WETSEM electron microscopy is presented. The use of wet SEM
      technology maintains cytological features of the thyroid cells, in the
      atmospheric electronic microscope chamber without the need for solidification.
      Images are presented from normal and pathological thyroid specimens showing
      subcellular elements unavailable to the cytopathologist by light microscopy. Of
      24 samples, 18 were adequate for clinical evaluation. In 16 of these 18
      specimens, we could find features compatible with the final histological or
      cytological diagnosis (post-hoc). In two cases, the cell features were too unique
      to be interpretable. Because this procedure is relatively simple, there is
      potential for the use of this technology as an adjunct to light microscopy in
      clinical and research settings.

PMID- 17042686
TI  - Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle
      aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists.
AB  - INTRODUCTION: Guidelines on thyroid fine-needle aspiration biopsy (FNABs)
      reporting calls for unambiguous diagnostic terminology in order to maximize
      treatment. This study evaluates how pathologists follow the guidelines and
      clinicians understand the diagnostic categories in terms of patient care. DESIGN:
      Survey 1 asked pathologists who perform/interpret FNABs which of "atypical,"
      "indeterminate," "suspicious," and "nondiagnostic" they routinely use. Survey 2
      asked clinicians who treat thyroid nodules to correlate these categories to the
      options of "negative FNAB/follow-up," "repeat FNAB," and "proceed to surgery."
      The anonymous, voluntary results were entered into a database and analyzed. MAIN
      OUTCOME: Pathologists' and clinicians' response rates were 70% and 35%,
      respectively. Survey 1: 27% of pathologists used three, 27% used one, and 44%
      used two categories. Survey 2: 98% clinicians would repeat the FNAB with a
      "nondiagnostic" and 96% opted for surgery with a "suspicious" diagnosis.
      "Indeterminate" prompted 58% to repeat the FNAB and 32% to send the patient to
      surgery. "Atypical" would lead 37% to repeat the FNAB and 52% to send the patient
      to surgery. CONCLUSIONS: Pathologists actively use the terminology "suspicious,"
      "indeterminate," or "atypical," which cause confusion in some clinicians. These
      results support the need for a more standardized terminology for FNAB reporting
      and education of the clinicians on that terminology.

PMID- 17042687
TI  - Thyroid disorders in employees of a nuclear power plant.
AB  - BACKGROUND: The thyroid gland is a potential target organ for radiation-related
      damage. The aim of this analysis was to investigate the association between
      occupational exposure to ionizing radiation and the risk of autoimmune thyroid
      disease as well as thyroid nodules and dysfunction in workers of a former nuclear
      power station. METHODS: Seventy-one male power station workers 38 to 57 years of
      age who had been exposed to a lifetime dose in the upper allowed range
      (accumulated lifetime dose 70 to 400 mSv) were compared to a population-based
      sample of 670 males who were not exposed to occupational radiation. Thyroid
      ultrasound was performed by the same observers. Laboratory parameters were
      analyzed in a central laboratory. RESULTS: After controlling analyses for age and
      further relevant confounders no significant differences with respect to thyroid
      nodules and markers of autoimmune thyroid disease were detected between exposed
      and nonexposed individuals. However, nuclear power plant employees had higher
      odds for elevated serum thyrotropin (TSH) levels than the reference group (odds
      ratio 4.54; 95% confidence interval 1.43; 13.91). CONCLUSIONS: Workers of a
      nuclear power plant with occupational exposure to ionizing radiation within the
      upper allowed dose range have an increased risk of elevated serum TSH levels.
      Further studies are required to confirm possible effects of occupational exposure
      to radiation on thyroid function.

PMID- 17042688
TI  - The relative frequency in which empiric dosages of radioiodine would potentially
      overtreat or undertreat patients who have metastatic well-differentiated thyroid
      cancer.
AB  - The dosage of (131)I for the treatment of metastatic well-differentiated thyroid
      cancer is typically selected empirically. Benua and Leeper implemented a method
      to estimate the maximum dosages of (131)I that could be administered to a patient
      so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was
      defined as 200 rads (cGy) to the blood. The objective of this study was to
      determine the frequency of (131)I treatments in which the patient (1) would have
      exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive
      higher dosages of (131)I thereby delivering a potentially higher radiation
      absorbed dose to their metastases (i.e., undertreatment) had the patient been
      administered various assumed empiric dosages of (131)I. The dosimetrically
      determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the
      blood (MTD) were tabulated at our facility. Data were then grouped to determine
      the percentage of patients who would have received less than or more than the MTD
      for various assumed empiric dosages of (131)I. A total of 127 dosimetries were
      performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250
      mCi, and 300 mCi), the percentage of treatments for which patients would have
      exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and
      could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%,
      and 78%, respectively. A significant number of patients receiving various empiric
      dosages of (131)I may exceed 200 rads (cGy) to the blood (potential
      overtreating). Likewise, the majority of patients may be able to receive much
      higher dosages of (131)I relative to empiric dosages thereby delivering
      potentially higher radiation absorbed doses to the metastases without exceeding
      200 rads (cGy) to the blood (potential undertreating).

PMID- 17042689
TI  - Defective efficacy of retinoic acid treatment in patients with metastatic thyroid
      carcinoma.
AB  - Radioiodine (I-131) therapy is of proven efficacy for differentiated thyroid
      carcinoma. However, its efficacy relies on specific uptake mechanisms, which may
      be lost during the evolution of the disease. Attempts to increase the iodine
      uptake of such tumors have been made using retinoic acid because it exerts
      redifferentiating effects on thyrocytes. This study aims to assess the capability
      of the retinoic acid (RA) treatment to reinforce iodine 131-irradiation efficacy
      for metastatic and progressive multi-irradiated thyroid cancer. In this clinical
      prospective study, 11 patients (mean age +/- 1 SD = 61 +/- 12 years, sex ratio
      M/F = 5/6) with a progressive disease despite iterative surgery and iodine
      irradiations were treated with 13-cis-retinoic acid (1.5 mg/kg day) over 8 weeks
      prior to I-131 irradiation. The redifferentiating effect of RA was evaluated by
      serum thyroglobulin (Tg) monitoring during RA treatment and qualitative analysis
      of iodine uptake on the post-therapeutic whole body scan. The clinical usefulness
      of RA treatment was assessed by clinical follow-up, Tg monitoring, and tumor
      size. No serious event that could possibly be related to the treatment was
      reported. The mean follow up time was 24.2 +/- 12 months (range 3-46 months).
      Iodine uptake was only slightly improved in two patients. Nevertheless, the
      clinical benefits of RA seem to be very poor. Five patients died of a metastatic
      disease. Five others presented new clinical evidences of a progressive disease.
      In conclusion, this prospective study demonstrates the absence of efficacy of I
      131 irradiation combined with RA for the treatment of patients with aggressive,
      rapidly growing metastatic thyroid cancer. Thus, patients with highly aggressive
      disease, rapidly growing in a short period from 2 to 6 months, should not be
      considered for RA therapy.

PMID- 17042690
TI  - Time trends of incidence rates of thyroid cancer in Israel: what might explain
      the sharp increase.
AB  - BACKGROUND: Worldwide changes in the incidence, histological type, and prognosis
      of thyroid cancer (TC) have been observed. Regional differences in the spectrum
      of TC may be related to genetic factors, ionizing radiation, lifestyle, and
      nutritional iodine, as well as to the availability of medical services. METHODS:
      Analysis of records of 5864 TC patients (diagnosed between 1982 and 2001),
      retrieved from the Israel National Cancer Registry. RESULTS: The age-standardized
      incidence rate (ASR per 100,000 persons) of TC among Jewish women in 2001 was
      12.45 (higher than generally reported in the world) and 3.68 among Jewish men.
      There was a significant increase in the ASR for TC between 1982 and 2001 in the
      Jewish population (by 101% among women and by 25% among men, p < 0.01 for both),
      mainly due to papillary carcinoma. TC incidence increased in the non-Jewish
      population from 2.33 to 6.02 in women (p < 0.05) and from 1.13 to 2.49 in men (p
      > 0.05). TC incidence was similar among immigrants from Europe and America
      arriving in Israel before 1990 or after 1990 for both genders. An improved 5-year
      survival was noted in patients diagnosed between 1992 and 1996 in comparison to
      patients diagnosed earlier: 1982-1986 (86% versus 78%, p < 0.01). CONCLUSIONS: A
      marked increase in TC incidence over the last two decades (mainly due to
      papillary carcinoma) has been noted in different Israeli subpopulations, being
      the highest in Jewish women. The increase trends were similar regardless of
      gender or ethnicity. The reasons for this rise in TC incidence and improvement in
      the survival are probably multifactorial and may relate partly to increased
      diagnostic vigilance and changes in clinical practice.

PMID- 17042691
TI  - Differential evolution of thyroid peroxidase and thyrotropin receptor antibodies
      in Graves' disease: thyroid peroxidase antibody activity reverts to pretreatment
      level after carbimazole withdrawal.
AB  - In this study, we compared the evolution of thyroid peroxidase antibody (TPOAb)
      and thyroid-stimulating antibody (TSAb) activities before, during, and after
      treatment of Graves' disease (GD) with carbimazole. TPOAb and TSAb were measured
      in sera from 75 patients with GD, during an 18-month block-replace regimen and
      after drug withdrawal (12, 24, and 36 months). At diagnosis, TPOAb were present
      in 85% of the patients versus 99% for TSAb. During the treatment, TPOAb values
      and prevalence significantly decreased, as observed with TSAb. After drug
      withdrawal, TPOAb levels increased once again to reach the pretreatment values,
      whereas TSAb remained unchanged. TPOAb values and prevalence at drug withdrawal
      were not significantly different between patients who remained euthyroid and
      those who had a relapse of hyperthyroidism. In contrast, TSAb values and
      prevalence were higher at drug withdrawal in relapse patients. In conclusion,
      TPOAb and TSAb changes are similar during GD treatment by carbimazole but diverge
      after drug withdrawal. TPOAb might reflect autoimmune perturbations independently
      of the clinical status and of the thyroid-stimulating activity.

PMID- 17042692
TI  - Impaired enteral levothyroxine absorption in hypothyroidism refractory to oral
      therapy after thyroid ablation for papillary thyroid cancer: case report and
      kinetic studies.
AB  - We present a 49-year-old patient suffering from hypothyroidism (thyrotropin
      [TSH], 20-80 mU/L) refractory to oral levothyroxine (LT(4)) substitution after
      total thyroidectomy and radioiodine therapy for papillary thyroid cancer.
      Extensive, repetitive work-up excluded small bowel, liver, and pancreatic disease
      and drug interactions. Triiodothyronine/thyroxine (T(3)/T(4)) antibodies were
      negative and reverse T(3) levels were normal. Supervised absorption tests of
      several LT(4) preparations in increasing dosages (250-1500 microg/d) confirmed an
      insufficient rise in serum T(4) levels following oral drug administration. Thus,
      intravenous LT(4) application (5 times per week) was commenced to restore at
      least normal range TSH levels. Repetition of absorption tests 1 year later, after
      a documented period of more than 3 months of stable euthyroidism, showed a
      considerable improvement of intestinal LT(4) uptake. Subsequently, the patient
      was managed on large doses of oral LT(4) (1500-2100 microg/d) alone, but this was
      found to be insufficient so that continuous intravenous LT(4) was administered
      via a morphine pump device to ultimately achieve stable euthyroidism. Of note, at
      4-year follow-up there was no evidence of recurrent or metastasized papillary
      thyroid cancer. The reason for the disturbed intestinal LT(4) absorption in this
      patient remains unresolved. However, we would like to suggest the possibility of
      a specific intestinal uptake deficit, which will only become apparent in the case
      of previous thyroid ablation.

PMID- 17042693
TI  - Burkitt's lymphoma presenting as a rapidly growing thyroid mass.
AB  - A 53-year-old man was admitted to the hospital because of tracheal compressive
      symptoms from a rapidly expanding thyroid mass. The patient first noticed the
      nodule less than a week prior to admission. Thyroid tests were normal. A fine
      needle aspiration (FNA) biopsy showed a monotonous population of intermediate
      sized lymphoid cells with scant cytoplasm suspicious for lymphoma. Twelve hours
      later an emergent computed tomography (CT) scan confirmed left tracheal deviation
      with compression, however, there were no signs of tumor invasion. The patient
      received emergent CHOP (clophosphamide, adriamycin, vincristine, prednisone) and
      rituxan therapy. His mass completely resolved within 36 hours. Bone marrow biopsy
      provided the final diagnosis of stage IV Burkitt's lymphoma and his therapy was
      changed to hyper CVAD-R chemotherapy (cytoxan, vincristine, adriamycin,
      dexamethasone, rituxan). The patient's hospital course was complicated by tumor
      lysis syndrome that was managed by hydration and allopurinol. To our knowledge,
      this is only the second reported case of Burkitt's lymphoma presenting as a
      thyroid mass. His presentation highlights the urgency in diagnosis and provides
      an opportunity to review a rare type of primary thyroid lymphoma.

PMID- 17042694
TI  - Needle tract implantation of follicular neoplasm after fine-needle aspiration
      biopsy: report of a case.
AB  - We herein report a 28-year-old woman with a follicular neoplasm showing
      subcutaneous needle tract implantation. One month after fine-needle aspiration
      biopsy (FNAB) for a tumor measuring 2.5 cm, the patient became aware of a
      subcutaneous nodule measuring about 1 cm at the needle insertion site. FNAB smear
      of this nodule showed poorly cohesive clusters of follicular cells with nuclear
      crowding, overlapping and resetting with some microfollicular architecture. Total
      thyroidectomy and resection of the subcutaneous nodule were performed. Although
      there was no capsular or vascular invasion of the nodule, the lesion was
      diagnosed as follicular carcinoma because of the subcutaneous seeding. Ki-67
      labeling indices of the thyroid nodule and implanted tumor were higher than 5%.
      Furthermore, although galectin-3 was completely negative in the thyroid nodule,
      it was heterogeneously positive in the implanted tumor. It is therefore suggested
      that high cell proliferating activity as a characteristic of the original nodule
      and the subsequently obtained invasive characteristic of the implanted tumor
      contributed to this event. To date, there has not been any recurrence of the
      implanted lesion. Because implanted follicular carcinoma can be surgically
      removed, this complication should not impair the usefulness of FNAB.

PMID- 17042695
TI  - Coregistered iodine-131 single photon emission computed tomography/computed
      tomography reveals dedifferentiation in a metastatic follicular thyroid
      carcinoma.

PMID- 17042696
TI  - Extraskeletal Ewing sarcoma mimicking a thyroid nodule.

PMID- 17042700
TI  - Lessons learned, funded research, integrity--what does it all mean?

PMID- 17042702
TI  - Telethinking: with James A. Brink, M.D. [interview by Vicki Glaser].

PMID- 17042703
TI  - Cost effectiveness, safety, and satisfaction with video telepsychiatry versus
      face-to-face care in ambulatory settings.
AB  - Videoconference telepsychiatry provides an alternative for the psychiatric
      treatment of mental health patients who reside in remote communities. The
      objective of this study was to compare institutional ambulatory and
      hospitalization costs, treatment adherence, patient and physician satisfaction,
      and treatment safety between mental healthcare via videoconferencing and care
      provided in person. Data collected for 1 year of telepsychiatry treatment was
      compared to that of the preceding year and a matched comparison group. Twenty
      nine patients from Or Akiva and 20 patients from Reut Hostel in Hadera who met
      the inclusion criteria agreed to participate; 24 and 15 patients, respectively,
      completed the study. Forty-two matched patients, who continued face-to-face
      interviews, comprised the comparison group. Drop-out patients and those who did
      not consent to telepsychiatry treatment were not involved. During the year of
      telepsychiatry treatment, patients and physicians were satisfied and treatment
      was safe. However, 1 hour of telepsychiatry treatment was more expensive than
      face-to-face care, and a tendency of increased hospitalizations was noted.
      Adherence ratios before and during telepsychiatry treatment were similar, but
      were twice as high versus the comparison group. The limited sample size precludes
      the drawing of definite conclusions, and further studies involving a larger study
      population and longer duration of investigation is warranted.

PMID- 17042704
TI  - The accident and emergency department virtual consulting room.
AB  - The goal was to describe the development of the Virtual Consulting Room (VcR), a
      unique intranet-based guidance application providing direct access to local
      specialist knowledge, and to evaluate its usability and whether it has the
      potential to educate staff while working in the Accident and Emergency (A&E)
      department. Duty staff of the A&E Department, The Royal Free Hospital, London,
      participated in a prospective observational study. Two hundred and twenty
      consecutive patients were identified from the triage section of their casualty
      card as having a presenting complaint that featured in the VcR. These casualty
      cards were highlighted with a red sticker alert and a short questionnaire
      attached. Members of staff were invited to consult with the VcR after assessing
      each patient by clicking on an icon located on the department's computer
      desktops. No prior training was provided. The questionnaire was completed in 103
      of 220 (46.8%) patients. The VcR was used in the management of 38 of 220 (17.3%)
      patients. In 21 of 38 (55.3%), users reported the VcR supported clinical decision
      making, in 20 of 38 (52.6%) the VcR improved knowledge and in 11 of 38 (28.9%)
      the VcR helped directly influence the decision to discharge the patient. In 2 of
      38 (5.3%) users changed their decision to refer and in 1 of 38 (2.6%)
      investigations were altered. This evaluation indicates that A&E clinicians
      accessing the VcR found it easy to use and educational in the workplace.

PMID- 17042705
TI  - Teleconsultation for cardiac patients: a comparison between nurses and
      physicians: the SHL experience in Israel.
AB  - The absence of randomized studies on sufficiently large patient cohorts precludes
      the drawing of any firm conclusions on the comparative performance between nurses
      and physicians in transtelephonic triage and consultations and in diagnostic and
      management decision-making. We conducted such a comparative study at the SHL
      telemedicine facility. This facility also provides face-to-face medical
      management for its subscribers by means of mobile intensive care units (MICUs)
      staffed by physicians. The outcome of calls that came between 7:00 AM and 11:00
      PM throughout the study year and that were handled at random by specially trained
      physicians (n = 15) or nurses (n = 35) were analyzed. Of 48,707 subscribers who
      fulfilled the study entry criteria 25,106 used the service at least once,
      producing 88,103 calls (81,817 handled by nurses and 6,286 by physicians).
      Teleconsultations were sufficient for most of the cases (80.13%). There were no
      significant differences between the performance of nurses and physicians
      regarding demographics (age, gender) and medical diagnoses of the applicants. The
      nurses' performance and decisions were comparable to those of physicians with
      respect to teleconsultations, medically justified dispatches of an MICU, repeated
      calls to the center and mortality during the week after the index call, although
      the duration of the physicians' telephone consultations was longer. Delegation of
      equal authority to nurses and physicians in triage and consultation in
      telecardiology results in equivalent and highly satisfactory medical care in a
      system in which subscribers receive service orchestrated from a single center of
      telecommunications.

PMID- 17042706
TI  - Eye contact in medical examinations using videophones.
AB  - In Japan, approximately 12,000,000 cellular phones with a videophone function
      have been distributed and are becoming an important part of the telemedicine
      infrastructure. By eye movement analysis, we investigated the effectiveness of
      eye contact using cellular videophones during medical interviews. Three male
      volunteers acted as first-time patients and were filmed using a high-resolution
      camera. The video of each of these volunteers was converted into pictures of
      three different sizes-70 cm x 40 cm (large picture), 26 cm x 20 cm (medium
      picture), and 14 cm x 12 cm (small picture)-and viewed on a 32-inch video
      monitor. The large, medium, and small pictures were considered to represent an
      actual medical interview, an interview via a television conference system, and an
      interview via a cellular videophone, respectively. Nine doctors watched these
      pictures, and their eye movements were recorded with a gaze-point recorder. After
      watching the videos, the doctors evaluated quality of three size pictures.
      Standard deviation values of the gaze point coordinates decreased with the
      picture size. However, a very low decrease was observed in the time ratio, during
      which the gaze point was on the face (eye contact rate); the rate was 92.2%
      (large picture), 91.8% (medium picture), and 85.1% (small picture). No
      statistical difference was observed between the values of the medium and small
      pictures. Subjective evaluations yielded low scores in the small pictures. The
      relatively high rate of eye contact rate in the small pictures suggests that a
      cellular videophone will be a good tool for telemedicine, although the usage by
      which the subjective evaluations can be improved should be determined by doctors.

PMID- 17042707
TI  - Osteosarcoma: evaluation of information on the internet.
AB  - The information about osteosarcoma on the existing websites was examined. The
      purpose of this study was to evaluate the quality of Internet information
      available to patients on the topic of osteosarcoma. The secondary purpose was to
      rank the identified websites with respect to the caliber of relevant information
      provided by the websites sponsors' identity. A great many of people in the world
      "surf" the World Wide Web, searching for medical information. The information on
      the Internet varies dramatically in terms of content and quality for lack of
      uniformed standard with respect to the medical publications on the Internet. Five
      search engines searched the search terms "osteosarcoma." The first 25 links
      displayed by each engine were evaluated for a theoretical total of 125 websites.
      According to the information context, sponsor identity we evaluated each website.
      An information quality score of 0 to 26 was generated for each site. A score of
      20 or greater was thought to be "high-quality" information website. Eighty-nine
      unique websites were identified, among which only 8 (9%) scored 20 or more on the
      information quality score; 32 scored 10 or less. The overall mean information
      quality score was 11.5. The websites with highest mean scores were academic
      organization and affiliated hospitals of university. The quality of Internet
      information on osteosarcoma is variable. Less than 10% of relevant websites were
      of high information value. The rank list of high quality websites from our
      information quality score should provide useful information of osteosarcoma.

PMID- 17042708
TI  - Psychiatrists' satisfaction with telepsychiatry.
AB  - The purpose of this evaluation study was to learn more about psychiatrists'
      satisfaction with telepsychiatry. Telepsychiatry will succeed only if
      psychiatrists are satisfied with this service delivery method and offer it to
      their patients. While telepsychiatry appears to be effective and most patients
      report that they are satisfied with it, less information is available about
      factors that lead to psychiatrists' satisfaction. We interviewed psychiatrists
      who treat rural/frontier patients and asked them to describe factors that
      encouraged or discouraged their use of telepsychiatry. Only 4 were mostly
      satisfied with telepsychiatry and all offered suggestions for improving this
      delivery method. Most agreed that it was a hardship for many of their patients to
      travel 100 to 750 roundtrip miles over a 1-3 day period for a 20-minute
      consultation and that telepsychiatry could be a lifeline to many of them.
      Nevertheless, they identified significant technical and interpersonal barriers
      that discouraged their use of telepsychiatry.

PMID- 17042709
TI  - Development of a broadband telehealth system for critical care: process and
      lessons learned.
AB  - A broadband telehealth system has been developed for supporting critical care
      services between a major referral hospital and a rural hospital by transmitting
      very high-quality, realtime multimedia information, including images, audio and
      real-time video, over an Internet Protocol (IP)-based network. The technical
      design team took an iterative and user-centred approach toward the system design.
      Usability tests with scenario analysis were incorporated into the development
      process to produce a system that operates seamlessly in the critical care
      environment. Careful analysis of the reliability of the system was incorporated
      into the clinical protocols for integration into existing work practices. The use
      of high-quality multimedia data, consideration of human factors early in the
      design process, and incorporation of proper development approaches were critical
      for the success of the system design.

PMID- 17042710
TI  - Group tele-exercise for improving balance in elders.
AB  - This study was to assess the level of acceptance and efficacy of a group tele
      exercise program designed for balance impaired elders to improve balance and
      reduce fear of falling. The program would allow a group of elderly subjects to
      participate in a structured, interactive, and supervised exercise class from
      their own homes through a videoconferencing system. A total of 17 independent
      living elderly subjects (mean age, 81 +/- 8 years) participated in the study. An
      Internet-based videoconferencing device (VCD) was installed in each subject's
      home, allowing real-time video and audio communication with the exercise
      instructor and all other participants. The exercise was in the form of Tai Chi
      Quan, three times per week for 15 weeks. The main study measures included
      exercise compliance, level of acceptance and satisfaction, and the effectiveness
      of the exercise program on balance, fear of falling, and general health. Three
      subjects dropped out of the study. For those remaining, the average compliance
      was 78% (range, 51% to 98%). All subjects were able to operate the VCD
      independently, and expressed earnest interest in continuing tele-exercise
      programs in the future. There were significant improvement (p < 0.05)
      postexercise in fear of falling score (18%), single leg stance time (43%), Up-and
      Go time (21%), and body sway during quiet stance (>8%). This study has
      demonstrated that the group tele-exercise program is acceptable and welcomed by
      elders, and is effective for improving balance and reducing fear of falling.

PMID- 17042711
TI  - Patient satisfaction levels during teleophthalmology consultation in rural South
      India.
AB  - The application of new technologies for analysis of retinal images, neural
      networks for automated retinopathy grading, and teleophthalmology have been shown
      to have great value in ophthalmology. India has only one ophthalmic surgeon for
      every 107,000 population. Given this situation, teleophthalmology can play a
      vital role in addressing to the eye care needs of the country. The objective of
      this study was to assess patient satisfaction levels and factors influencing it
      during teleophthalmology consultation in India. A patient satisfaction
      questionnaire was prepared to assess the prominent aspects of patient
      satisfaction, including teleophthalmology screening, confidence in the technology
      used to transfer the fundus images, comprehensiveness of information available to
      the doctor in the central hub, and graded the opinion regarding the
      teleophthalmology. A cross-sectional survey among patients who attended a
      teleophthalmology screening conducted across eight villages in rural Tamilnadu.
      Responses were then subjected to qualitative analysis and conclusions made. The
      number of respondents was 348. Of this, 56.4% were males. The mean age of was 50
      +/- 17 years. Age ranged from 2 years to 83 years. 44.4% of the respondents were
      satisfied with teleophthalmology screening. (95% confidence interval [CI]: 38.58%
      49.42%) No association was found between age, gender, education, and occupation,
      respectively, with satisfaction levels. We found that patients who asked
      questions during the screening were 2.18 times more likely to be satisfied with
      teleophthalmology than those who did not (odds ratio [OR] = 2.19, 95% CI 1.37
      3.5). This study highlights sentiments of the rural subjects when they underwent
      teleophthalmology consultations. This study provides valuable insights about
      patient's preferences and satisfaction levels with this newer technology.

PMID- 17042712
TI  - Research recommendations for the american telemedicine association.
AB  - The American Telemedicine Association (ATA) convened a panel of experts to
      generate a research agenda for the telemedicine community to further support and
      promote the long-term acceptance and use of telehealth. Three principles to guide
      research and four key areas within which research is greatly needed were
      identified. These four areas are technical, clinical, human factors and
      ergonomics, and economic analyses. It is the hope of the panel that the research
      recommendations put forth in this document will give investigators the
      inspiration, tools and goals to make this happen.

PMID- 17042713
TI  - Evolution of telemedicine from an applied communication perspective in the United
      States.
AB  - Telemedicine, the use of telecommunication technologies to provide health
      services over some distance, has a history that spans more than five decades.
      Technological development and deployment have been interrelated with shifting
      paradigmatic views. This paper proposes that telemedicine has evolved through
      three generations that began with telemedicine as a communication medium to
      complement traditional services to a technology of automation and decision tools
      that expands the scope and range of health services and creates a unique health
      communication context. This paper provides a literature review and overviews
      three proposed evolutionary stages for telemedicine to date, namely synchronous
      versus asynchronous modalities, data transfer and storage, and automating
      decision making and robotics. Finally, we conclude with a discussion of the
      barriers for telemedicine and a call for engineers to join with social scientists
      and medical professionals to set an agenda for future telemedicine development.

PMID- 17042714
TI  - Recruitment and enrollment of rural and urban medically underserved elderly into
      a randomized trial of telemedicine case management for diabetes care.
AB  - Our goal was to identify reasons for enrollment or refusal to participate in a
      randomized trial of telemedicine case management of diabetes. We performed a
      prospective survey of participants and non-participants during recruitment for
      the Informatics for Diabetes Education and Telemedicine (IDEATel) study, a
      randomized trial of telemedicine case management of diabetes mellitus in
      medically underserved elderly. There were two recruitment areas: urban New York
      City, and rural upstate New York. A Participant Questionnaire (PQ) was
      administered at the baseline IDEATel visit, and a Non-Participant Questionnaire
      (NPQ) was administered during the recruitment telephone call. Both questionnaires
      listed possible responses; subjects could choose more than one response or give
      their own. Of 1,660 IDEATel participants, 99.7% completed the PQ. Most frequent
      reason for participation was the belief that the technology could help them (52%
      and 42% of urban and rural respondents, respectively). Of the 2,231 subjects
      refusing participation, 28% answered the NPQ (90% of respondents were from rural
      area). Most frequent reasons not to participate in the rural area were being too
      busy (23%), and discomfort with the technology (22%), and in the urban area the
      belief that the technology could not help them (71%), discomfort with it (52%),
      and not liking to participate in studies (52%). In multivariate analysis (rural
      respondents only), knowing how to use a computer was an independent predictor of
      participation (p < 0.001). In conclusion, perceptions and beliefs regarding
      technology, including the expectation to benefit from it, played an important
      role in the decision to participate.

PMID- 17042715
TI  - Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded
      rats.
AB  - HLU suppressed bone formation and resulted in bone loss in the tibial metaphysis
      of 6-month-old male rats. A human therapeutic dose of intermittent PTH (1
      microg/kg/day) prevented the skeletal changes associated with HLU. INTRODUCTION:
      Skeletal unloading of skeletally mature rats results in trabecular thinning in
      the proximal tibial metaphysis, which is in part caused by a decrease in bone
      formation. We examined the efficacy of PTH in preventing the detrimental skeletal
      effects that occur with hindlimb unloading (HLU). MATERIALS AND METHODS: Six
      month-old male Fisher 344 rats were HLU and treated with vehicle or recombinant
      human PTH(1-34) at 1, 5, 20, or 80 microg/kg/day for 2 weeks. The bone response
      was measured by microCT analysis of bone structure, histomorphometric analysis of
      static and dynamic bone parameters, and Northern blot analysis of mRNA levels for
      bone matrix proteins. The PTH-treated HLU animals were compared with vehicle
      treated HLU and pair-fed normal weight-bearing controls. RESULTS: Unloading
      resulted in a decrease in cancellous bone volume that was caused in part by a
      dramatic 83% decrease in bone formation. All dose rates (1-80 microg/kg/day) of
      human PTH(1-34) significantly increased bone formation rates compared with
      vehicle-treated HLU controls. There was a dose response, and the highest dose
      rate of the hormone increased bone formation compared with normal weight-bearing
      rats by 708% (p < 0.0001). The increases in bone formation were accompanied by
      increases in mRNA levels for type 1 collagen, osteocalcin, and osteonectin. Also,
      treatment with PTH resulted in increases in mineral apposition rate and double
      labeled perimeter, but the latter was disproportionally increased at high dose
      rates. A therapeutic dose of PTH (1 microg/kg/day) prevented disuse-induced
      trabecular thinning, whereas high-dose PTH (80 microg/kg/day) increased
      trabecular thickness compared with normal weight-bearing rats. CONCLUSIONS: These
      findings reveal that administration of a therapeutic dose of PTH to HLU rats
      prevents the decrease in bone formation and trabecular thinning, whereas high
      dose rates of the hormone increase bone formation and trabecular thickness to
      values that exceed normal values.

PMID- 17042717
TI  - Clodronate reduces the incidence of fractures in community-dwelling elderly women
      unselected for osteoporosis: results of a double-blind, placebo-controlled
      randomized study.
AB  - A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800
      mg showed that the incidence of clinical fractures was decreased by 20% in 5596
      elderly women unselected for osteoporosis. The effect occurred in the absence of
      systematic calcium and vitamin D supplementation and was observed across a wide
      range of BMDs. INTRODUCTION: To date, most studies with bisphosphonates have
      reported on their use in individuals selected to be at high risk for fracture
      usually by the presence of low BMD or a prior fragility fracture, usually of the
      spine. We wished to determine the effect of the bisphosphonate, clodronate, on
      the rate of fractures in women > or =75 years of age living in the community.
      MATERIALS AND METHODS: Women > or =75 years of age living in the general
      community in South Yorkshire and North Derbyshire, identified from general
      practice registers, were recruited by letter of invitation to a randomized,
      double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching
      placebo daily over 3 years. The main outcomes were the incidences of hip and any
      clinical fracture. RESULTS: Of the 5579 elderly women included in the intention
      to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year
      treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in
      the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71-1.47). Clodronate did,
      however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%]
      versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68-0.94). The
      incidence of osteoporosis-associated nonhip fractures was also significantly
      decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57-0.87). The ability of
      clodronate to reduce the risk of osteoporotic fracture was independent of
      baseline BMD, but the number needed-to-treat was lower in the presence of
      osteoporosis. CONCLUSIONS: Oral daily clodronate can prevent fractures without
      significant adverse effects in elderly women living in the general community. The
      effect on hip fracture risk is not significant, but an effect similar to that at
      other nonvertebral sites cannot be excluded. This study suggests that
      antiresorptive therapies can reduce fracture incidence in high-risk individuals
      even in the presence of a normal or osteopenic BMD.

PMID- 17042716
TI  - RGS12 is essential for RANKL-evoked signaling for terminal differentiation of
      osteoclasts in vitro.
AB  - How RANKL evokes [Ca(2+)](i) oscillations and leads to osteoclast differentiation
      is unclear. We identified a new signaling protein, RGS12, and found that RGS12 is
      essential for [Ca(2+)](i) oscillations and osteoclast differentiation induced by
      RANKL. RGS12 may play a critical role in the RANKL-evoked PLCgamma-calcium
      channels-[Ca(2+)](i) oscillation-NFAT2 pathway. INTRODUCTION: RANKL-induced
      [Ca(2+)](i) oscillations play a switch-on role in NFAT2 expression and osteoclast
      differentiation. However, RANKL evokes [Ca(2+)](i) oscillations and leads to
      osteoclast differentiation by an unknown mechanism. In this study, we identified
      a new RANKL-induced signaling protein, regulator of G signaling protein 12
      (RGS12), and investigated its effect on osteoclast differentiation in vitro.
      MATERIALS AND METHODS: We used a genome-wide screening approach to identify genes
      that are specifically or prominently expressed in osteoclasts. To study the role
      of the RGS12 in osteoclast differentiation, we used vector and lentivirus-based
      RNAi gene silencing technology to silence the RGS12 gene in the monocyte
      progenitor cell lines and primary bone marrow-derived monocytes (BMMs). The
      interaction between RGS12 and N-type calcium channels was elucidated using co
      immunoprecipitation and immunoblotting. RESULTS: We found that RGS12 was
      prominently expressed in osteoclast-like cells (OLCs) induced by RANKL. This
      result was further confirmed at both the mRNA and protein level in human
      osteoclasts and mouse OLCs. Silence of RGS12 expression using vector and
      lentivirus based RNA interference (RNAi) impaired phosphorylation of
      phospholipase C (PLC)gamma and blocked [Ca(2+)](i) oscillations, NFAT2
      expression, and osteoclast differentiation in RANKL-induced RAW264.7 cells and
      BMMs. We further found that N-type calcium channels were expressed in OLCs after
      RANKL stimulation and that RGS12 directly interacted with the N-type calcium
      channels. CONCLUSIONS: These results reveal that RGS12 is essential for the
      terminal differentiation of osteoclasts induced by RANKL. It is possible that
      RGS12 regulates osteoclast differentiation through a PLC gamma-calcium channel
      [Ca(2+)](i) oscillation-NFAT2 pathway.

PMID- 17042719
TI  - Horse slaughter ban clears House.

PMID- 17042720
TI  - Echoes the desire for comparative medicine.

PMID- 17042721
TI  - A proposal for the assessment of the quality of food supply veterinary medical
      education.

PMID- 17042722
TI  - What is your diagnosis? Inflammatory epithelium and ceruminous gland
      adenocarcinoma.

PMID- 17042723
TI  - What is your diagnosis? Disorder of the swim bladder.

PMID- 17042725
TI  - Animal behavior case of the month.

PMID- 17042724
TI  - Anesthesia case of the month. Hypotension.

PMID- 17042726
TI  - Employment of female and male graduates of US veterinary medical colleges, 2006.

PMID- 17042727
TI  - Detection of Borrelia burgdorferi DNA in tissues from dogs with presumptive Lyme
      borreliosis.
AB  - OBJECTIVE: To develop a quantitative PCR assay for detection of Borrelia
      burgdorferi DNA in formalin-fixed, paraffin-embedded tissues; compare results of
      this assay with results of immunohistochemical staining of tissues from
      seropositive dogs; and determine whether B burgdorferi DNA could be detected in
      renal tissues from dogs with presumptive Lyme nephritis. DESIGN: Cohort study.
      SAMPLE POPULATION: Archived tissue samples from 58 dogs. PROCEDURES: A
      quantitative PCR assay was performed on formalin-fixed, paraffin-embedded tissue
      sections from the dogs. Results were compared with results of immunohistochemical
      staining, B burgdorferi serostatus, clinical signs, and necropsy findings.
      RESULTS: 38 dogs were classified as having positive or equivocal results for Lyme
      borreliosis, and 20 were classified as having negative results on the basis of
      clinical signs, serologic findings, and pathologic abnormalities. Borrelia
      burgdorferi DNA was amplified from tissue samples from only 4 (7%) dogs, all of
      which had been classified as having positive or equivocal results for Lyme
      borreliosis and had signs of presumptive Lyme nephritis. Results of PCR assays of
      renal tissue were positive for only 1 dog, and there was no agreement between
      results of immunohistochemical staining (ie, detection of B burgdorferi antigen)
      and results of the PCR assay (ie, detection of B burgdorferi DNA) for renal
      tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that detection of
      B burgdorferi DNA in formalin-fixed, paraffin-embedded tissues is feasible, but
      that intact B burgdorferi DNA is rarely found in tissues from naturally infected
      dogs, even tissues from dogs with presumptive Lyme borreliosis. Further, findings
      support the contention that Lyme nephritis may be a sterile, immune complex
      disease.

PMID- 17042728
TI  - Toxicosis associated with ingestion of quick-dissolve granulated chlorine in a
      dog.
AB  - CASE DESCRIPTION: A dog was referred for treatment after ingestion of quick
      dissolve chlorine granules intended for use in a swimming pool. CLINICAL
      FINDINGS: At evaluation 18 hours after ingestion of the granules, the dog had
      tachypnea, signs of depression, approximately 5% dehydration, oral mucositis, and
      a productive cough. Increased respiratory tract sounds and wheezes were ausculted
      in all lung fields. Complete blood count revealed erythrocytosis and lymphopenia.
      Serum biochemical analyses revealed mildly high activities of hepatic enzymes and
      creatine kinase. Arterial blood gas concentrations were consistent with hypoxemia
      and hyperventilation. Thoracic radiography revealed widespread pulmonary alveolar
      infiltrates predominantly affecting the ventral portions of both lungs,
      consistent with noncardiogenic pulmonary edema secondary to aspiration of the
      granulated chlorine. TREATMENT AND OUTCOME: Initial treatment included IV
      administration of an electrolyte solution with supplemental KCl, ranitidine,
      furosemide, cefotaxime, buprenorphine, and supplemental oxygen. Subsequent
      treatment included administration of meloxicam and an endoscopically placed
      percutaneous gastrostomy tube. Endoscopic examination revealed esophagitis and
      mild gastritis; therefore, metoclopramide and sucralfate were also administered.
      Fifteen days later, the gastrostomy tube was removed prior to discharge;
      endoscopic examination revealed grossly normal esophageal and gastric mucosa, and
      thoracic radiography revealed complete resolution of the lung lesions. CLINICAL
      RELEVANCE: Although ingestion of granulated chlorine is rare in veterinary
      patients, the resulting disease processes are common and can be treated
      successfully.

PMID- 17042730
TI  - Evaluation of risk factors for development of secondary glaucoma in dogs: 156
      cases (1999-2004).
AB  - OBJECTIVE: To determine the immediately antecedent cause of secondary glaucoma
      and the prevalence of secondary glaucoma with anterior uveitis or lens
      dislocation in dogs. DESIGN: Retrospective case series. ANIMALS: 156 dogs with
      secondary glaucoma. PROCEDURES: Cause of glaucoma was determined from records.
      Breed, age, sex, and neuter status of all dogs with secondary glaucoma were
      compared with the general hospital population. The prevalence of secondary
      glaucoma in dogs with a primary diagnosis of lens dislocation or anterior uveitis
      during the same period was determined. RESULTS: Secondary glaucoma was diagnosed
      in 156 of 2,257 (6.9%) dogs examined because of ophthalmic disease and was
      bilateral in 33 (21.2%) of those dogs. In 31 (94%) bilaterally affected dogs, the
      antecedent cause was the same in both eyes. Common causes of secondary glaucoma
      were non-surgical anterior uveitis (44.9%), anterior uveitis associated with
      prior phacoemulsification (15.8%), and lens dislocation (15.2%). Parson Russell
      Terriers, Poodles, Boston Terriers, Cocker Spaniels, Rhodesian Ridgebacks, and
      Australian Cattle Dogs had diagnoses of secondary glaucoma more often than
      expected, compared with the reference population. Age, sex, neuter status, and
      laterality were not associated with secondary glaucoma. The prevalence of
      secondary glaucoma in dogs with lens dislocation or uveitis was 15% or 17%,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Glaucoma develops secondary to
      many intraocular diseases, particularly uveitis and lens dislocation. Diagnosis
      of these diseases should prompt frequent monitoring of intraocular pressure,
      regardless of signalment.

PMID- 17042731
TI  - Effect of rostrocaudal mobility of the mandible on feed digestibility and fecal
      particle size in horses.
AB  - OBJECTIVE: To evaluate the effect of rostrocaudal mobility (RCM) of the mandible
      during extension and flexion of the atlanto-occipital joint on weight gain, feed
      digestibility, and fecal particle size in horses. DESIGN: Randomized controlled
      trial. ANIMALS: 34 pregnant mares housed in 1 barn. PROCEDURES: Horses were
      randomized into a treatment (n = 17) or control (17) group. All horses were
      sedated, and the distance between the rostral portions of the upper and lower
      incisor arcades was determined during extension and flexion of the atlanto
      occipital joint; mandibular RCM was calculated as the difference between these
      values. In the treatment group, measurements were made after dental floating.
      Body weight was recorded 1 day before dental floating and at intervals after
      mandibular RCM determination for a period of 24 weeks. Feces were collected from
      each horse during two 5-day periods. Samples of feed and feces were analyzed to
      determine feed digestibility; particle size analysis was performed on dried fecal
      samples. RESULTS: Data obtained from each group of horses revealed that RCM of
      the mandible did not affect weight gain, feed digestibility, or particle size in
      feces; there were no differences among breeds. Controlling for age and number of
      dental lesions did not significantly affect results. CONCLUSIONS AND CLINICAL
      RELEVANCE: In horses, RCM of the mandible did not appear to affect weight gain,
      feed digestibility, or fecal particle size. On the basis of these and other
      published data, the assumption that dental abnormalities affect digestion
      detrimentally in horses needs to be reevaluated.

PMID- 17042733
TI  - Antimicrobial susceptibility patterns of respiratory tract pathogens from sheep
      and goats.
AB  - OBJECTIVE: To determine the antimicrobial susceptibility of common respiratory
      tract pathogens from sheep and goats. DESIGN: Cross-sectional study. SAMPLE
      POPULATION: 41 respiratory tract isolates from sheep and 36 isolates from goats.
      PROCEDURES: Disk diffusion assay was used to determine antimicrobial
      susceptibility of isolates to amoxicillin-clavulanic acid, ceftiofur,
      ciprofloxacin, florfenicol, and tetracycline. Minimum inhibitory concentrations
      of florfenicol for these isolates were determined by use of the microbroth
      dilution technique. RESULTS: The most common isolates were Pasteurella multocida
      (n = 28) and Mannheimia haemolytica (39). All isolates were susceptible to
      amoxicillin-clavulanic acid, ceftiofur, ciprofloxacin, and florfenicol. Five
      percent (4/77) of isolates were resistant to tetracycline. CONCLUSIONS AND
      CLINICAL RELEVANCE: Susceptibility of respiratory tract pathogens isolated from
      sheep and goats to commonly used antimicrobial drugs in this study was high.
      Treatment of these species for bacterial respiratory tract disease is likely not
      complicated by antimicrobial resistance.

PMID- 17042734
TI  - Serum IgG and total protein concentrations in dairy calves fed two colostrum
      replacement products.
AB  - OBJECTIVE: To evaluate effects of 2 commercially available colostrum replacement
      products on serum IgG and total protein concentrations in dairy calves. DESIGN:
      Prospective clinical trial. ANIMALS: 84 Holstein bull calves from a single dairy.
      PROCEDURES: Calves were randomly assigned to be given 4 quarts of colostrum
      (group 1; n = 21), 2 packages of a colostrum replacement product (product A;
      group 2; 21), 1 package of a different colostrum replacement product (product B;
      group 3; 21), or 2 packages of product B (group 4; 21). Treatments were given
      within 3 hours after birth, and blood samples were collected 24 hours later and
      submitted for determination of serum total protein and IgG concentrations.
      RESULTS: Group 1 calves had significantly higher serum total protein and IgG
      concentrations than did calves in the other 3 groups. However, the percentage of
      calves with adequate passive transfer (ie, serum IgG concentration > 1,000 mg/dL)
      was not significantly different among groups 1 (90%), 3 (81%), and 4 (95%). In
      contrast, only 10% of calves in group 2 had adequate passive transfer. It was
      predicted that calves fed product B that had serum total protein concentrations >
      5.2 g/dL would have serum IgG concentrations > 1,000 mg/dL at least 90% of the
      time. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that product B could
      be considered as an alternative to colostrum in dairy calves, but product A
      failed to routinely provide adequate serum IgG concentrations when fed according
      to label directions.

PMID- 17042735
TI  - The multiple roles of osteoclasts in host defense: bone remodeling and
      hematopoietic stem cell mobilization.
AB  - Bone remodeling by bone-forming osteoblasts and bone-resorbing osteoclasts
      dynamically alters the bone inner wall and the endosteum region, which harbors
      osteoblastic niches for hematopoietic stem cells. Investigators have recently
      elucidated mechanisms of recruitment and mobilization; these mechanisms consist
      of stress signals that drive migration of leukocytes and progenitor cells from
      the bone marrow reservoir to the circulation and drive their homing to injured
      tissues as part of host defense and repair. The physical bone marrow vasculature
      barrier that is crossed by mobilized cells actively transmits chemotactic signals
      between the blood and the bone marrow, facilitating organ communication and cell
      trafficking. Osteoclasts play a dual role in regulation of bone resorption and
      homeostatic release or stress-induced mobilization of hematopoietic
      stem/progenitor cells. In this review, we discuss the orchestrated interplay
      between bone remodeling, the immune system, and the endosteal stem cell niches in
      the context of stem cell proliferation and migration during homeostasis, which
      are accelerated during alarm situations.

PMID- 17042736
TI  - High dietary phosphate intake reduces bone strength in the growing rat skeleton.
AB  - Nutrition influences peak bone mass development in early adulthood. The effect of
      high dietary phosphate intake on the growing skeleton of 1-month-old male rats (n
      = 30) was assessed in an 8-week intervention. High dietary phosphate intake
      increased bone remodeling and impaired bone material properties, diminishing bone
      mechanical strength. INTRODUCTION: High dietary phosphate intake is typical in
      the Western diet. Abundant phosphate intake enhances parathyroid secretion and
      bone metabolism. To study the influence of high dietary phosphate intake on
      growing bone homeostasis and structure, we submitted growing rats to experimental
      diets that varied in their phosphate content. MATERIALS AND METHODS: One-month
      old intact male rats (n = 30) were fed a control diet (Ca:P 1:1) or an
      experimental diet of either Ca:P 1:2 or Ca:P 1:3 for 8 weeks. At the beginning
      and the end of the study period, the right femurs were measured using DXA. Double
      labeling with tetracycline injection was performed 12 and 2 days before death.
      After death, hind legs were cut loose. Left femurs were processed for
      histomorphometry. Right femurs were measured with pQCT. Mechanical testing was
      performed on the right femoral neck and tibial shaft. Six right tibias were
      analyzed with microCT. Serum PTH, calcium, and phosphate contents were analyzed.
      RESULTS: High-phosphate intake impaired growth of the animal, limited bone
      longitudinal growth, and restricted femur BMC and BMD build-up. Osteoclast
      number, osteoblast perimeter, and mineral apposition rate were increased, and
      trabecular area and width were decreased. Phosphate decreased femur midshaft
      total bone BMD, cortical bone BMD, and mean cortical thickness. High-phosphate
      diet reduced femoral neck and tibial shaft ultimate strength and tibia stiffness
      and toughness. In addition, serum PTH increased. CONCLUSIONS: High dietary
      phosphate intake reduced growth, skeletal material, and structural properties and
      decreased bone strength in growing male rats. Adequate calcium could not overcome
      this.

PMID- 17042737
TI  - Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass,
      body composition, and growth: a 7-year prospective study into young adulthood.
AB  - The long-term effects on bone and fat mass in children with endogenous CS are
      unknown. In 14 children followed for 3-7 years into young adulthood after cure of
      CS, whereas bone mass largely recovered, persisting increases in total body and
      visceral fat suggests an increase risk of the metabolic syndrome. INTRODUCTION:
      Endogenous Cushing syndrome (CS) is associated with decreased bone mass and
      increased central fat mass. Whereas bone mass seems to improve after successful
      treatment, little is known about whether central fat persists. MATERIALS AND
      METHODS: This was a prospective study of 14 children (10 girls and 4 boys) and
      adolescents with CS who were successfully treated and remained eucortisolemic.
      Growth, puberty, bone mass, and body composition were evaluated at baseline and
      during regular follow-up for 3 years and in seven children for a further 4 years
      of remission to assess final adult height (FH), BMI, bone mass, and body
      composition. RESULTS: CS compromised growth, leading to about a -0.8 SD loss of
      FH and 0.9 SD increase in weight and BMI. BMD apparent density (BMAD) SD Score
      (SDS) at the lumbar spine (LS) at diagnosis were -1.8 and -1.25, respectively,
      and after 3 years of follow-up approached the mean with no further increase
      apparent up to 7 years of follow-up. Whereas hip BMD SDS increased from -1.3 at
      diagnosis to -0.40 at 3 years and 0 at 7 years of follow-up, femoral neck BMAD
      remained at or around 0 SDS at diagnosis and during follow-up. BMI was >25
      kg/m(2) in five of seven adult subjects, most of whom were women. Total body fat
      and the ratio of visceral to subcutaneous was abnormally high in the majority of
      these subjects, whereas LS volumetric BMD was -0.7 SDS. CONCLUSIONS: Despite
      remission of CS, children and adolescents have significant alterations in body
      composition that result in a small but significant decrease in bone mass and
      increase in visceral adiposity. Although bone mass largely recovers after
      endogenous CS, changes in total and visceral fat suggest these subjects are at
      increased risk of the metabolic syndrome. Therefore, long-term monitoring of body
      fat and bone mass is mandatory after treatment of CS.

PMID- 17042738
TI  - Effects of teriparatide and alendronate on vertebral strength as assessed by
      finite element modeling of QCT scans in women with osteoporosis.
AB  - FE modeling was used to estimate the biomechanical effects of teriparatide and
      alendronate on lumbar vertebrae. Both treatments enhanced predicted vertebral
      strength by increasing average density. This effect was more pronounced for
      teriparatide, which further increased predicted vertebral strength by altering
      the distribution of density within the vertebra, preferentially increasing the
      strength of the trabecular compartment. INTRODUCTION: Teriparatide 20 microg/day
      (TPTD) and alendronate 10 mg/day (ALN) increase areal, measured by DXA, and
      volumetric, measured by QCT, lumbar spine BMD through opposite effects on bone
      remodeling. Using finite element (FE) modeling of QCT scans, we sought to compare
      the vertebral strength characteristics in TPTD- and ALN-treated patients.
      MATERIALS AND METHODS: A subset of patients (N = 28 TPTD; N = 25 ALN) from the
      Forteo Alendronate Comparator Trial who had QCT scans of the spine at baseline
      and postbaseline were analyzed. The QCT scans were analyzed for compressive
      strength of the L(3) vertebra using FE modeling. In addition, using controlled
      parameter studies of the FE models, the effects of changes in density, density
      distribution, and geometry on strength were calculated, a strength:density ratio
      was determined, and a response to bending was also quantified. RESULTS: Both
      treatments had positive effects on predicted vertebral strength characteristics.
      At least 75% of the patients in each treatment group had increased strength of
      the vertebra at 6 months compared with baseline. Patients in both treatment
      groups had increased average volumetric density and increased strength in the
      trabecular bone, but the median percentage increases for these parameters were 5-
      to 12-fold greater for TPTD. Larger increases in the strength:density ratio were
      also observed for TPTD, and these were primarily attributed to preferential
      increases in trabecular strength. CONCLUSIONS: These results provide new insight
      into the effects of these treatments on estimated biomechanical properties of the
      vertebra. Both treatments positively affected predicted vertebral strength
      through their effects on average BMD, but the magnitudes of the effects were
      quite different. Teriparatide also affected vertebral strength by altering the
      distribution of density within the vertebra, so that overall, teriparatide had a
      5-fold greater percentage increase in the strength:density ratio.

PMID- 17042739
TI  - Craniosynostosis-associated gene nell-1 is regulated by runx2.
AB  - We studied the transcriptional regulation of NELL-1, a craniosynostosis-related
      gene. We identitifed three OSE2 elements in the NELL-1 promoter that are directly
      bound and transactivated by Runx2. Forced expression of Runx2 induces NELL-1
      expression in rat calvarial cells. INTRODUCTION: We previously reported the
      upregulation of NELL-1 in human craniosynostosis and the overexpression of Nell-1
      in transgenic animals that induced premature suture closure associated with
      increased osteoblast differentiation. To study the transcriptional regulation of
      NELL-1, we analyzed the 5' flanking region of the human NELL-1 gene. We
      identified three osteoblast specific binding elements 2 (OSE2) sites (A, B, and
      C) within 2.2 kb upstream of the transcription start site and further studied the
      functionality of these sites. MATERIALS AND METHODS: An area of 2.2 kb and a
      truncated 325 bp, which lacked the three OSE sites, were cloned into a luciferase
      reporter gene, and co-transfected with Runx2 expression plasmid. The three OSE2
      sites were individually mutated and co-transfected with Runx2 expression plasmid
      into Saos2 cells. Gel shifts and supershifts with Runx2 antibodies were used to
      determine specific binding to OSE2 sites. CHIP assays were used to study in vivo
      binding of Runx2 to the Nell-1 promoter. Runx2 expression plasmid was transfected
      into wildtype and Runx2(-/-) calvarial cells. Nell-1, osteocalcin, and Runx2
      expression levels were measured using RT-PCR. RESULTS: Addition of Runx2 dose
      dependently increased the luciferase activity in the human NELL-1 promoter
      luciferase p2213. The p325 truncated NELL-1 construct showed significantly lower
      basal level of activity. Nuclear extract from Saos2 cells formed complexes with
      site A, B, and C probes and were supershifted with Runx2 antibody. Mutation of
      sites A, B, and C significantly decreased basal promoter activity. Furthermore,
      mutation of sites B and C had a blunted response to Runx2, whereas mutation of
      site A had a lesser effect. Runx2 bound to NELL-1 promoter in vivo. Transfection
      of Runx2 in rat osteoblasts upregulated Nell-1 and Ocn expression, and in Runx2
      null calvarial cells, both Nell-1 and Ocn expression were rescued. CONCLUSIONS:
      Runx2 directly binds to the OSE2 elements and transactivates the human NELL-1
      promoter. These results suggest that Nell-1 is likely a downstream target of
      Runx2. These findings may also extend our understanding of the molecular
      mechanisms governing the pathogenesis of craniosynostosis.

PMID- 17042740
TI  - Fission yeast cytoskeletons and cell polarity factors: connecting at the cortex.
AB  - Cell polarity is a fundamental property of cells from unicellular to
      multicellular organisms. Most of the time, it is essential so that the cells can
      achieve their function. The fission yeast Schizosaccharomyces pombe is a powerful
      genetic model organism for studying the molecular mechanisms of the cell polarity
      process. Indeed, S. pombe cells are rod-shaped and cell growth is restricted at
      the poles. The accurate localization of the cell growth machinery at the cell
      cortex, which involves the actin cytoskeleton, depends on cell polarity pathways
      that are temporally and spatially regulated. The importance of interphase
      microtubules and cell polarity factors acting at the cortex of cell ends in this
      process has been shown. Here, we review recent advances in knowledge of molecular
      pathways leading to the establishment of a cellular axis in fission yeast. We
      also describe the role of cortical proteins and mitotic cytoskeletal
      rearrangements that control the symmetry of cell division.

PMID- 17042741
TI  - Bacterial protein toxins and lipids: role in toxin targeting and activity.
AB  - All bacterial toxins, which globally are hydrophilic proteins, interact first
      with their target cells by recognizing a surface receptor, which is either a
      lipid or a lipid derivative, or another compound but in a lipid environment.
      Intracellular active toxins follow various trafficking pathways, the sorting of
      which is greatly dependent on the nature of the receptor, notably lipidic
      receptor or receptor embedded into a distinct environment such as lipid
      microdomains. Numerous other toxins act locally on cell membrane. Indeed,
      phospholipase activity is a common mechanism shared by several membrane-damaging
      toxins. In addition, many toxins active intracellularly or on cell membrane
      modulate host cell phospholipid pathways. Unusually, a few bacterial toxins
      require a lipid post-translational modification to be active. Thereby, lipids are
      obligate partners of bacterial toxins.

PMID- 17042742
TI  - Bacterial protein toxins and lipids: pore formation or toxin entry into cells.
AB  - Lipids are hydrophobic molecules which play critical functions in cells, in
      particular, they are essential constituents of membranes, whereas bacterial
      toxins are mainly hydrophilic proteins. All bacterial toxins interact first with
      their target cells by recognizing a surface receptor, which is either a lipid or
      a lipid derivative, or another compound but in a lipid environment. Most
      bacterial toxins are PFTs (pore-forming toxins) which oligomerize and insert into
      the lipid bilayer. A common mechanism of action involves the formation of a beta
      barrel structure, resulting from the assembly of individual beta-hairpin(s) from
      individual monomers. An essential step for intracellular active toxins is to
      translocate their enzymatic part into the cytosol. Some toxins use a
      translocation mechanism based on pore formation similar to that of PFTs, others
      undergo a yet unclear 'chaperone' process.

PMID- 17042745
TI  - Jose Ruiz-Herrera - biographical sketch.

PMID- 17042743
TI  - A feedback transcriptional mechanism controls the level of the arginine/lysine
      transporter cat-1 during amino acid starvation.
AB  - The adaptive response to amino acid limitation in mammalian cells inhibits global
      protein synthesis and promotes the expression of proteins that protect cells from
      stress. The arginine/lysine transporter, cat-1, is induced during amino acid
      starvation by transcriptional and post-transcriptional mechanisms. It is shown in
      the present study that the transient induction of cat-1 transcription is
      regulated by the stress response pathway that involves phosphorylation of the
      translation initiation factor, eIF2 (eukaryotic initiation factor-2). This
      phosphorylation induces expression of the bZIP (basic leucine zipper protein)
      transcription factors C/EBP (CCAAT/enhancer-binding protein)-beta and ATF
      (activating transcription factor) 4, which in turn induces ATF3. Transfection
      experiments in control and mutant cells, and chromatin immunoprecipitations
      showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an
      AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1
      gene, which functions both in the endogenous and in a heterologous promoter. ATF4
      and C/EBPbeta activated transcription when expressed in transfected cells and
      they bound as heterodimers to the AARE in vitro. The induction of transcription
      by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with
      C/EBPbeta. These results suggest that the transient increase in cat-1
      transcription is due to transcriptional activation caused by ATF4 followed by
      transcriptional repression by ATF3 via a feedback mechanism.

PMID- 17042746
TI  - Fungal yapsins and cell wall: a unique family of aspartic peptidases for a
      distinctive cellular function.
AB  - A novel class of aspartic peptidases known as fungal yapsins, whose first member
      ScYps1p was identified more than a decade ago in Saccharomyces cerevisiae, is
      characteristically modified by the addition of a glycophosphatidylinositol moiety
      and has a preference for cleaving substrates C-terminally to mono- and paired
      basic residues. Over the years, several other members, first in S. cerevisiae and
      then in other fungi, have been identified. The implication of fungal yapsins in
      cell-wall assembly and/or remodelling had been suspected for many years. However,
      it is only very recently that studies performed on S. cerevisae and Candida
      albicans have confirmed their importance for cell-wall integrity. Here, we review
      16 years of research, covering all fundamental aspects of these unique enzymes,
      in an effort to track their functional significance. We also propose a
      nomenclature for fungal yapsins based on their sequence identity with the
      founding members of this family, the S. cerevisiae yapsins.

PMID- 17042747
TI  - Candida biofilms on implanted biomaterials: a clinically significant problem.
AB  - In recent years there has been an increasing appreciation that microbial biofilms
      are ubiquitous, which has resulted in a number of studies on infectious diseases
      from a biofilm perspective. Biofilms are defined as structured microbial
      communities that are attached to a surface and encased in a matrix of
      exopolymeric material. A wide range of biomaterials used in clinical practice
      have been shown to support colonization and biofilm formation by Candida spp.,
      and the increase in Candida infections in the last decades has almost paralleled
      the increase and widespread use of a broad range of medical implant devices,
      mainly in populations with impaired host defenses. Formation of Candida biofilms
      has important clinical repercussions because of their increased resistance to
      antifungal therapy and the ability of cells within biofilms to withstand host
      immune defenses. Further recognition and understanding of the role of Candida
      biofilms in human infection should help in the clinical management of these
      recalcitrant infections.

PMID- 17042748
TI  - Use of DNA microarray technology and gene expression profiles to investigate the
      pathogenesis, cell biology, antifungal susceptibility and diagnosis of Candida
      albicans.
AB  - The use of DNA microarrays is becoming the method of choice for assaying gene
      expression, particularly as costs and complexity are being reduced as the
      technology becomes more widespread and better standardized. A DNA array is
      nothing but a collection of probes fixed on a solid support. The probes can be
      PCR products of ORFs or short intragenic oligonucleotides deposited or
      synthesized in situ by photolithographic methods. To date, sequencing projects
      for fungal genomes have yielded 10 complete genomes and 21 whole shotgun
      sequences, including Candida albicans strain SC5314. Sequencing of the C.
      albicans genome has led to the construction of whole-genome DNA microarrays for
      in vitro transcription profiling by several universities and companies. The use
      of microarray or DNA chip techniques for Candida research has started recently
      but the number of studies using this technology is increasing rapidly, in order
      to address important remaining questions about pathogenesis, cell biology,
      antifungal susceptibility, and diagnosis.

PMID- 17042749
TI  - Immunolocalization of chitin synthases in the phytopathogenic dimorphic fungus
      Ustilago maydis.
AB  - Conserved polypeptides of the chitin synthase genes UmCHS3 and UmCHS6 from the
      phytopathogenic fungus Ustilago maydis were utilized as immunogens to obtain
      polyclonal antibodies that were purified by affinity procedures. Because of their
      similarities at the regions encoded by either polypeptide, it was concluded that
      anti-Chs3 antibodies recognized both Chs3 and Chs4 chitin synthases, whereas anti
      Chs6 antibodies recognized Chs6 and Chs8 polypeptides. These antibodies were used
      to analyze the localization of the corresponding chitin synthases in U. maydis
      cells, using both indirect immunofluorescence microscopy and immunoelectron
      microscopy with colloidal-gold-labeled secondary antibodies. It was observed that
      chitin synthase proteins were accumulated both in the surface and in the
      cytoplasm of the fungal cells. Electron microscopy images revealed the
      accumulation of clusters of gold particles in vesicles, providing evidence for
      the possible origin and destination of chitin synthases in the fungal cells.

PMID- 17042750
TI  - An ectophosphatase activity in Cryptococcus neoformans.
AB  - There is increasing evidence in the literature showing that fungal pathogens
      express biologically active ectoenzymes. The expression of surface phosphatases
      at the cell surface of Cryptococcus neoformans, the etiologic agent of
      cryptococcosis, was evaluated in the present study. Different isolates of C.
      neoformans express ectophosphatase activity, which is not influenced by capsule
      size or serotype. The cryptococcal enzyme is an acid phosphatase, inhibited by
      classic inhibitors of ectophosphatases, including ammonium molybdate and sodium
      salts of fluoride and orthovanadate. Only the inhibition of enzyme activity
      caused by sodium orthovanadate has been shown to be irreversible. The
      cryptococcal ectoenzyme is also inhibited by Zn2+ and inorganic phosphate, the
      final product of reactions catalyzed by phosphatases. The ectophosphatase from C.
      neoformans efficiently releases phosphate groups from different phosphorylated
      amino acids, giving a higher rate of phosphate removal when phosphothreonine is
      used as a substrate. Yeast cells with irreversibly inhibited ectophosphatases are
      less capable of adhering to animal epithelial cells than fungi fully expressing
      enzyme activity, suggesting that ectoenzyme expression can contribute to the
      pathogenesis of C. neoformans.

PMID- 17042751
TI  - Cloning and characterization of Sapp2p, the second aspartic proteinase isoenzyme
      from Candida parapsilosis.
AB  - The human fungal pathogen Candida parapsilosis possesses at least three genes
      encoding secreted aspartic proteinases. Whereas the Sapp1p isoenzyme has already
      been biochemically characterized, the SAPP2 and SAPP3 gene products have not. The
      Sapp2p precursor, pro-Sapp2p, was therefore expressed in Escherichia coli and
      purified. Autoactivation of pro-Sapp2p in acidic conditions was inefficient and
      resulted in a protein extended by eight amino acids at the N-terminus
      (Sapp2p(+8)). The correct promature junction KR/SSPSS was cleaved by trypsin or
      by a membrane-bound Kex2-like proteinase from Candida parapsilosis. The mature
      Sapp2p obtained by the assisted activation was proteolytically active. Its
      activity was more than twofold higher than that of the self-processed protein
      species Sapp2p(+8), as measured by the hemoglobin cleavage test. The substrate
      specificity of Sapp2p differs from that of Sapp1p. Peptides containing aromatic
      residues in the P1 and P1' positions are cleaved poorly by Sapp2p. A fluorogenic
      substrate was synthesized to facilitate further studies.

PMID- 17042752
TI  - Absence of Gup1p in Saccharomyces cerevisiae results in defective cell wall
      composition, assembly, stability and morphology.
AB  - Saccharomyces cerevisiae Gup1p and its homologue Gup2p, members of the
      superfamily of membrane-bound O-acyl transferases, were previously associated
      with glycerol-mediated salt-stress recovery and glycerol symporter activity.
      Several other phenotypes suggested Gup1p involvement in processes connected with
      cell structure organization and biogenesis. The gup1Delta mutant is also
      thermosensitive and exhibits an altered plasma membrane lipid composition. The
      present work shows that the thermosensitivity is independent of glycerol
      production and retention. Furthermore, the mutant grows poorly on salt, ethanol
      and weak carboxylic acids, suggestive of a malfunctioning membrane potential.
      Additionally, gup1Delta is sensitive to cell wall-perturbing agents, such as
      Calcofluor white, Zymolyase, lyticase and sodium dodecyl sulphate and exhibits a
      sedimentation/aggregation phenotype. Quantitative analysis of cell wall
      components yielded increased contents of chitin and beta-1,3-glucans and lower
      amounts of mannoproteins. Consistently, scanning electron microscopy showed a
      strikingly rough surface morphology of the mutant cells. These results suggest
      that the gup1Delta is affected in cell wall assembly and stability, although the
      Slt2p/MAP kinase from the PKC pathway was phosphorylated during hypo-osmotic
      shock to a normal extent. Results emphasize the pleiotropic nature of gup1Delta,
      and are consistent with a role of Gulp1p in connection with several pathways for
      cell maintenance and construction/remodelling.

PMID- 17042753
TI  - Measurements of plasma membrane potential changes in Saccharomyces cerevisiae
      cells reveal the importance of the Tok1 channel in membrane potential
      maintenance.
AB  - K+ is one of the cations (besides protons) whose transport across the plasma
      membrane is believed to contribute to the maintenance of membrane potential. To
      ensure K+ transport, Saccharomyces cerevisiae cells possess several types of
      active and passive transporters mediating the K+ influx and efflux, respectively.
      A diS-C3(3) assay was used to compare the contributions of various potassium
      transporters to the membrane potential changes of S. cerevisiae cells in the
      exponential growth phase. Altogether, the contributions of six K+ transporters to
      the maintenance of a stable membrane potential were tested. As confirmed by the
      observed hyperpolarization of trk1 trk2 deletion strains, the diS-C3(3) assay is
      a suitable method for comparative studies of the membrane potential of yeast
      strains differing in the presence/absence of one or more cation transporters. We
      have shown that the presence of the Tok1 channel strongly influences membrane
      potential: deletion of the TOK1 gene results in significant plasma membrane
      depolarization, whereas strains overexpressing the TOK1 gene are hyperpolarized.
      We have also proved that plasma membrane potential is not the only parameter
      determining the hygromycin B sensitivity of yeast cells, and that the role of
      intracellular transporters in protecting against its toxic effects must also be
      considered.

PMID- 17042754
TI  - Implications of sterol structure for membrane lipid composition, fluidity and
      phospholipid asymmetry in Saccharomyces cerevisiae.
AB  - Sterols are essential components of the plasma membrane in eukaryotic cells.
      Nystatin-resistant erg mutants were used in the present study to investigate the
      in vitro effects of altered sterol structure on membrane lipid composition,
      fluidity, and asymmetry of phospholipids. Quantitative analyses of the wild type
      and mutants erg2, erg3 and erg6 revealed that mutants have lower sterol (free)-to
      phospholipid molar ratios than the wild type. Phosphatidylcholine content was
      decreased in erg2 and erg3 mutants; however, it was increased in erg6 strains as
      compared to normals. Phosphatidylserine content was increased in the erg6 mutant
      only. Fluorescence anisotropy decreased with temperature in both probes, and was
      lower for mutants than for the wild type, suggesting an increased freedom in
      rotational movement due to decreased membrane order. Investigation of changes in
      the aminophospholipid transbilayer distribution using two chemical probes,
      trinitrobenzene sulfonic acid and fluorescamine, revealed that the amounts of
      phosphatidylethanolamine derivatized by these probes were quite similar in both
      the wild type and various erg strains. The present findings suggest that adaptive
      responses in yeast cells with altered sterol structure are possibly manifested
      through changes in membrane lipid composition and fluidity, and not through
      transbilayer rearrangement of aminophospholipids.

PMID- 17042755
TI  - Production of Man5GlcNAc2-type sugar chain by the methylotrophic yeast Ogataea
      minuta.
AB  - The methylotrophic yeast Ogataea minuta IFO 10746 was selected as a suitable
      strain for producing human-compatible glycoproteins by means of analyses of its
      cell-wall mannoproteins. First, the OmURA3 gene encoding an orotidine-5'
      phosphate decarboxylase was cloned and disrupted to generate a host strain with a
      uracil auxotrophic marker. Second, both the promoters and the terminators from
      the OmAOX1 gene encoding an alcohol oxidase for an inducible promoter, or those
      from the OmTDH1 gene encoding a glyceraldehyde-3-phosphate dehydrogenase for a
      constitutive promoter, were isolated to construct an expression vector system for
      heterologous genes. Next, the OmOCH1 gene encoding a starting enzyme with alpha
      1,6-mannosyltransferase activity to form a backbone of the N-linked outer sugar
      chain peculiar to yeast was disrupted, and an alpha-1,2-mannosidase gene from
      Aspergillus saitoi with an endoplasmic reticulum retention signal (HDEL) under
      the control of the OmAOX1 promoter was introduced to convert the sugar chain to
      Man5GlcNAc2 in O. minuta. As a result, we succeeded in breeding a new
      methylotrophic yeast, O. minuta, producing a Man5GlcNAc2-high-mannose-type sugar
      chain as a prototype of a human-compatible sugar chain. We also elucidate here
      the usefulness of the strategy for producing human-compatible sugar chains in
      yeast.

PMID- 17042756
TI  - Effect of farnesol on Candida dubliniensis biofilm formation and fluconazole
      resistance.
AB  - Candida dubliniensis and Candida albicans are dimorphic fungal species with a
      number of pathogenic capabilities, including biofilm formation, systemic
      infection and development of fluconazole resistance. In this study, the ability
      of farnesol to disrupt these virulence capabilities was investigated. Biofilm
      assessment and susceptibility studies indicated antifungal and antibiofilm
      properties for farnesol on both species with a disruptive effect on the cell
      membrane. Synergy testing of farnesol and fluconazole in resistant strains
      resulted in reversal of fluconazole resistance, indicating a potential
      application for farnesol as an adjuvant therapeutic agent.

PMID- 17042757
TI  - Biofilm formation by Candida albicans mutants for genes coding fungal proteins
      exhibiting the eight-cysteine-containing CFEM domain.
AB  - Several features and functions of a Candida albicans gene, PGA10 (also designated
      as RBT51), coding for a putative polypeptide species belonging to a subset of
      fungal proteins containing an eight-cysteine domain referred as CFEM (Common in
      several Fungal Extracellular Membrane proteins), are described. The ORF of the
      gene (ORF19.5674) encoded a protein of 250 amino acids, with a predicted
      molecular mass of 25.17 kDa. The product of the PGA10 gene also exhibited some
      features reminiscent of a class II-type hydrophobin. Deletion of PGA10 resulted
      in a cascade of pleiotropic effects, mostly affecting cell-surface-related
      properties. Thus, the null pga10Delta mutant displayed an increased sensitivity
      to cell-wall-perturbing agents and formed fragile biofilms that appeared
      partially split and weakly attached to the substratum. The biofilm-forming
      ability of several C. albicans mutants with single, double and triple deletions
      of genes encoding other protein species also containing the CFEM domain (RBT5 and
      WAP1/CSA1) was determined. These mutants also exhibited an abnormal ability to
      form biofilms. Overall, the evidence presented here suggests that fungal proteins
      containing the CFEM domain (Pga10p/Rbt51p, Rbt5p and Wap1p/Csa1p) may play a key
      role in the formation, development and/or maintenance of the biofilm structure in
      C. albicans.

PMID- 17042758
TI  - An in vitro assay to study the transcriptional response during adherence of
      Candida albicans to different human epithelia.
AB  - Adhesion to mammalian epithelia is one of the prerequisites that are essential to
      accomplish pathogenesis of Candida albicans in the mammalian host. In this
      context C. albicans is able to adhere to a plethora of different cell types
      providing different microenvironments for colonization. To study the response of
      C. albicans adhering to different surfaces on the transcriptional level we have
      established an in vitro adhesion assay exploiting confluent monolayers of the
      human colorectal carcinoma cell line Caco-2 or epidermoid vulvo-vaginal A-431
      cells. Candida albicans very efficiently adheres to these epithelia growing as
      hyphae. Using whole-genome DNA microarrays comprising probes for almost 7000
      predicted ORFs we found that transcriptional profiles of C. albicans adhering to
      Caco-2 or to A-431 cells, although very similar, still significantly differ from
      those of Candida cells adhering to plastic surfaces. Differences became even more
      obvious when comparing C. albicans cells either growing in an adherent manner or
      in suspension culture. Correspondingly, we found for several cell surface genes,
      including PRA1, PGA23, PGA7 and HWP1, an adhesion-dependent induction of
      transcription. Obviously, C. albicans is able to respond specifically to very
      subtle differences in the environment during adhesion to various growth
      substrates.

PMID- 17042759
TI  - Rapid PCR-based test for identifying Candida albicans by using primers derived
      from the pH-regulated KER1 gene.
AB  - A PCR-based method in combination with a simple, reliable and inexpensive DNA
      extraction procedure for rapid detection of Candida albicans clinical isolates is
      described here. The extraction protocol is based on a combination of chemical
      (NaOH and detergents) and physical (boiling) treatments, thus avoiding many of
      the problems inherent in the currently available DNA extraction protocols
      (basically the use of expensive and/or toxic chemical reagents), and may be
      useful for daily clinical routine. The PCR-based system described here uses a
      single pair of primers (SC1F and SC1R) deduced from the C. albicans-specific KER1
      gene sequence. These primers amplify a 670-bp fragment of the KER1 gene. All the
      clinical C. albicans isolates generated the expected 670-bp amplicon. Other non
      albicans Candida species, including the azole-resistant C. krusei and C.
      glabrata, and the very closely related C. dubliniensis, failed to amplify any DNA
      fragment. The PCR results reported here suggest that amplification with SC1F and
      SC1R primers is species specific and, consequently, may be useful for
      specifically identifying C. albicans strains.

PMID- 17042760
TI  - Four-year evaluation of myocardial and liver iron assessed prospectively with
      serial MRI scans in young patients with beta-thalassaemia major: comparison
      between different chelation regimens.
AB  - This study was conducted in order to assess myocardial and liver iron
      concentrations (LICs) using serial magnetic resonance imaging (MRI) scans in
      patients with beta-thalassaemia major, over a 4-yr period, and consequently to
      compare the effectiveness of different chelation regimens. Fifty children and
      young adults with beta-thalassaemia major (27 boys and 23 girls) were recruited
      (mean age: 14.74 +/- 3.67 yr). All patients underwent detailed clinical
      examination, electrocardiography, echocardiography, myocardial and liver MRI at
      the beginning of the study, 2 and 4 yr after. Additionally, serum ferritin levels
      were regularly measured and data regarding LICs assessed by percutaneous liver
      biopsy were available in 26 patients. Both myocardial and liver MRI values showed
      a moderate inverse correlation with age (r = -0.379, P < 0.001 and r = -0.376, P
      < 0.001, respectively). Liver MRI was better correlated with serum ferritin
      concentrations (r = -0.342, P < 0.001) than myocardial MRI (r = -0.186, P =
      0.011). Liver MRI values were highly correlated with LICs derived from
      percutaneous liver biopsy (r = -0.863, P < 0.001), whereas myocardial MRI values
      did not correlate at all with measurements derived from echocardiography.
      Regarding iron chelation treatment, patients receiving combined therapy with
      deferiprone and deferoxamine (DFO) significantly reduced myocardial iron overload
      during the 4-yr study period, whilst patients in monotherapy with DFO showed a
      significant increase in LIC.

PMID- 17042761
TI  - Detection of early abnormalities in gastric function in first-degree relatives of
      patients with pernicious anemia.
AB  - BACKGROUND: Pernicious anemia (PA), as many other autoimmune disorders, has a
      trend to appear in other members of the family of the affected patients. Although
      this fact has been recognized since some decades ago, less is known about the
      frequency with which the abnormalities detected in the patients appear also in
      their relatives, the correlations that exist among these abnormalities and to
      what extent these markers of the disease relate to serum cobalamin concentration.
      SUBJECTS AND RESULTS: For these reasons we studied the values of some markers of
      PA in a group of 79 first-degree relatives and we detected that the most frequent
      abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase
      in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40
      (23.4% of cases). From a functional point of view, a decrease in hydrogen
      excretion in a magnesium breath test, indicative of achlorhydria, is also
      frequent (29.1%). The fall in cobalamin concentration runs in parallel with these
      abnormalities. The concentration of this vitamin was below normal levels in as
      much as 15.2% of cases. CONCLUSION: These findings emphasize the need for
      searching for the presence of occult or latent PA in relatives of patients with
      this diagnosis, not only to prevent the development of anemia but also to avoid
      other undesirable consequences of cobalamin deficiency.

PMID- 17042762
TI  - Effect of CD34 cell dose on hematopoietic reconstitution and outcome in 508
      patients with multiple myeloma undergoing autologous peripheral blood stem cell
      transplantation.
AB  - BACKGROUND: We analyzed the hematopoietic reconstitution and outcome of 508
      patients with multiple myeloma (MM) with respect to the number of CD34+ cells
      reinfused at our center. PATIENTS AND METHODS: Each cohort of 390 patients
      (unselected CD34+ cell transplant) and 118 patients (CD34+ selected transplant)
      was divided into four subgroups. Among the 390 transplantations, 86 patients
      received a high dose (HD-) of > or =6.50 x 10(6) unselected CD34+ cells/kg, 116
      patients a low dose (LD-) of <3.00 x 10(6) CD34+ cells/kg. Among the patients
      treated with CD34+ selected PBSC, 34 received > or =6.50 x 10(6) CD34+ cells/kg
      (HD+) and 16 <3.00 x 10(6) CD34+ cells/kg (LD+). RESULTS: HD- patients
      experienced a reduced median time to leukocyte (13 d vs. 14 d) (P < 0.001) and
      platelet reconstitution >20 x 10(9)/L (10 d vs. 12 d) (P < 0.001). Similarly, HD+
      showed a reduced median time to leukocyte (12 d vs. 15 d) (P < 0.001) and
      platelet recovery >20 x 10(9)/L (10 d vs. 11 d) (P = 0.058). CD34+ cell-dose was
      significant for long-term platelet recovery at day 360 (unselected transplant P =
      0.015, selected transplant P = 0.023). Number of transplanted CD34+ cells had no
      significant impact on transplant related mortality, overall survival or CR/PR
      rates within 100 d. In terms of supportive care the differences of high-/low-dose
      grafts were minimal. CONCLUSIONS: These results confirm that high doses of CD34+
      PBSC shorten hematopoietic reconstitution and reduce hospitalization.
      Nevertheless secure engraftment results from transplantation of 2.00-3.00 x 10(6)
      CD34+ cells/kg. As 60% of our pretreated patients are able to collect > or =5.00
      x 10(6) CD34+ cells/kg within a single leukapheresis, division into two or more
      freezing bags allows safe tandem transplantation in the majority of MM patients.

PMID- 17042764
TI  - Appraisal of current vitamin K dosing algorithms for the reversal of over
      anticoagulation with warfarin: the need for a more tailored dosing regimen.
AB  - Warfarin is the most commonly prescribed oral anticoagulant in the UK for the
      treatment and prevention of thromboembolic disorders. Vitamin K administration is
      an effective way of reversing excessive anticoagulation. Over-anticoagulated
      patients present with a wide range of international normalized ratio (INR) values
      and may respond differently to a fixed dose of vitamin K. Current dosing
      algorithms for vitamin K administration in the non-urgent treatment of over
      anticoagulation do not take this variability in response into account.
      Consequently, over a third of over-anticoagulated patients still remain outside
      their target INR 24 h after treatment. Such patients are therefore prone to
      either haemorrhage (if the patient is still over-anticoagulated) or
      thromboembolism (if the INR reversal is over-corrected). A number of factors such
      as patient age, body weight, co-morbidity, frailty, warfarin daily dose and
      CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the
      rate and extent of INR reversal. There is a need for a more individualized
      approach to the reversal of over-anticoagulation in asymptomatic or mildly
      haemorrhagic patients in order to improve the safety of warfarin therapy.

PMID- 17042765
TI  - Platelet autoantibodies are common in hepatitis C infection, irrespective of the
      presence of thrombocytopenia.
AB  - OBJECTIVE: To investigate the generation of platelet antibodies in hepatitis C
      virus (HCV)-infected individuals and their relation to the development to
      thrombocytopenia with the aim of using their detection as a diagnostic aid of
      immune thrombocytopenia in these patients. MATERIALS AND METHODS: We tested by
      the monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA)
      for the presence of platelet antibodies against specific glycoprotein (GP)
      targets (GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIIIb, GPV, and FcRgammaIIa) in 48 HCV
      infected individuals of various stages of disease and compared the results with
      those from 35 patients with alcoholic liver cirrhosis. RESULTS: Thirty-two HCV
      infected individuals (66%) had detectable platelet antibodies. The most common
      target was GPIIb/IIIa, but all other GP were also targets. Results were not
      different from patients with alcoholic liver cirrhosis. There was no correlation
      between antibodies and platelet counts, or the stage of disease, or the viral
      genotype, or a discernible influence of treatment with alpha-interferon.
      CONCLUSION: While platelet autoantibodies are common in individuals with HCV
      infection, their detection does not assist in the diagnosis of immune
      thrombocytopenia.

PMID- 17042766
TI  - Thrombotic thrombocytopenic purpura associated with renal failure after
      autologous transplantation for multiple myeloma successfully treated with
      rituximab.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome
      characterised by a dramatic onset requiring an urgent treatment with plasma
      exchange (PE). However, the prognosis is still dismal for PE related
      complications, a rate of failure and remarkable frequencies of relapse. TTP post
      transplantation is largely described as an outstanding, unusual complication of
      allogenic transplantation, but it is rarely mentioned after autologous
      transplantation. We describe a 62-year-old Caucasian patient who presented with
      TTP, accompanied by renal failure, after an autologous transplantation for
      multiple myeloma. PE together with hemodialysis was rapidly initiated but without
      any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal
      antibody,was reported to be effective, we administered four courses of Rituximab
      inducing a complete remission of TTP and subsequently of the renal failure. This
      response to Rituximab in TTP post transplantation is suggestive of a possible
      implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for
      an investigational approach in this settings.

PMID- 17042767
TI  - A novel Indian beta-thalassemia mutation in the CACCC box of the promoter region.
AB  - This is the first report of a previously undescribed mutation in Indian subjects
      of the CACCC box of promoter region for beta-globin, which in combination with a
      common mutation produces thalassemia major in the offspring of the family.

PMID- 17042768
TI  - Intrathecal donor lymphocyte infusion for the treatment of suspected refractory
      lymphomatous meningitis: a case report.
AB  - A 43-year-old female with large T-cell non-Hodgkin's lymphoma and central nervous
      system (CNS) involvement underwent HLA-identical-sibling peripheral blood stem
      cell transplantation (SCT) during her third complete remission. She presented a
      possible refractory CNS relapse 5 months after the transplant. She was then
      treated with intrathecal (IT) donor lymphocyte infusions (DLI). No side effects
      were observed after three DLI injections. The patient died 13 months later from
      infectious complications with no evidence of progressive disease. To our
      knowledge, this is the first case report of IT DLI for possible refractory
      lymphomatous meningitis.

PMID- 17042769
TI  - Individually determined dosing of filgrastim after autologous peripheral stem
      cell transplantation in patients with malignant lymphoma--results of a
      prospective multicentre controlled trial.
AB  - OBJECTIVES: To explore the safety and effectiveness of the individually
      determined application granulocyte-colony stimulating factor (G-CSF) after
      autologous peripheral blood stem cell transplantation (ASCT). METHODS: The
      administration of G-CSF from day +5 (arm A) was compared in a randomised,
      controlled trial with delayed, individually determined administration (G-CSF
      started when WBC >or= 0.5 x 10(9)/L and ANC >or= 0.1 x 10(9)/L or at day +10; arm
      B), and with placebo (arm C). RESULTS: One hundred and six patients, median age
      45 (range 21-64), all with malignant lymphoma treated with BEAM chemotherapy were
      analysed. A significant difference in the time to neutrophil engraftment and in
      the duration of neutropenia <0.5 x 10(9)/L and <1.0 x 10(9)/L was observed
      between the arms (P = 0.04-<0.0001) with a 1-d prolongation of the median
      durations in arm B in comparison with arm A but a 2-4-d prolongation in the
      placebo arm C in comparison with arm B. The median number and range of days to
      neutrophil engraftment >0.5 x 10(9)/L after graft re-infusion was 10 (9-14) in
      arm A; 11 (9-19) in arm B; and 14 (10-30) in arm C (P < 0.0001). Engraftment of
      platelets to >20 x 10(9)/L and >50 x 10(9)/L was significantly delayed in the
      arms using G-CSF in comparison with placebo (P = 0.04-0.002) without any increase
      in bleeding or in transfusion requirement. There was no difference in the
      incidence and duration of transplant-related complications and their treatment
      between the arms. CONCLUSIONS: Our study has confirmed the safety of individually
      determined administration of G-CSF. The optimal timing of G-CSF application after
      ASCT in patients with good-quality grafts is shortly before expected spontaneous
      engraftment.

PMID- 17042770
TI  - An antecedent diagnosis of refractory anemia with excess blasts has no influence
      on mobilization of peripheral blood stem cells and hematopoietic recovery after
      autologous stem cell transplantation in acute myeloid leukemia.
AB  - Several studies have reported data on factors influencing mobilization of
      peripheral blood stem cells (PBSC) in non-myeloid malignancies. On the contrary,
      data from patients with acute myeloid leukemia (AML) are very limited, in
      particular, as the impact of an antecedent diagnosis of refractory anemia with
      excess blasts (RAEB) on mobilization of PBSCs as well as hematopoietic recovery
      after autologous stem cell transplantation (ASCT) is concerned. We
      retrospectively analyzed a cohort of 150 consecutive AML patients in first
      complete remission in order to make a comparison between patients with de novo
      AML and secondary AML (s-AML) in terms of CD34 positive (CD34+) cells
      mobilization and number of leukapheresis needed to collect at least one single
      stem cell graft. Data concerning hematopoietic recovery after ASCT were also
      compared. The successful mobilization rate (>2 x 10(6) CD34+ cells/kg) was
      comparable between de novo AML patients (87%) and those with s-AML (76%), P:0.21.
      No statistically significant difference was found in terms of either median
      number of CD34+ cells collected (P:0.44) or CD34+ cells peak in peripheral blood
      (P:0.28). Both groups of patients needed a median of two apheresis (P:0.45) and
      no difference was found on the median number of CD34+ cells collected per single
      apheresis (P:0.59). Finally, neutrophil and platelet recovery after ASCT were
      comparable between the two groups. An antecedent diagnosis of RAEB has no impact
      on mobilization and collection of PBSCs in AML as well as on hematopoietic
      recovery after ASCT.

PMID- 17042771
TI  - Potentiation of erythroid abnormalities following macrophage depletion in aged
      rats.
AB  - OBJECTIVES: The effects of prolonged macrophage depletion on haematological
      parameters were investigated in aged rats and compared with those in young ones.
      METHODS: Four weekly i.v. injections of dichloromethylene diphosphonate
      containing liposomes (Cl2MDP-CL) were employed to achieve a prolonged depletion
      of bone marrow (BM) and spleen macrophages. The number of BM macrophages was then
      assessed by flow cytometry, whereas the spleen clearance function was judged by
      the elimination of oxidised red blood cells (RBC). Haematological parameters and
      signs of RBC ageing (reduced MCV, increased density and augmented 4.1a/4.1b
      membrane protein ratio) were determined. Finally, the recovery from phlebotomy
      induced acute anaemia was investigated. RESULTS: Following the Cl2MDP-CL
      treatment, in comparison with young rats, the aged animals showed: (i) reduced
      numbers of BM macrophages; (ii) greater impairment of spleen clearance function;
      (iii) similar anaemic condition and signs of RBC ageing; (iv) greater increase in
      white blood cell (WBC) numbers (mainly neutrophils). In addition, whereas aged
      control rats showed a recovery from phlebotomy-induced acute anaemia which was
      similar to that of the untreated young animals, in the aged-treated rats, a
      significantly diminished/delayed restoration of RBC, Hb and reticulocyte to
      normal values was observed, accompanied by a significantly higher increase in WBC
      numbers than in the other groups of animals. CONCLUSION: Haematological
      abnormalities because of Cl2MDP-CL-induced macrophage depletion are potentiated
      in aged rats in which the BM regenerative potential of the erythroid lineage as
      well as the clearance function of the spleen appear compromised. Thus, in aged
      rats, macrophage dysfunction is likely to interfere with erythroid homeostasis
      particularly during haemopoietic stress.

PMID- 17042772
TI  - H63D homozygotes with hyperferritinaemia: Is this genotype, the primary cause of
      iron overload?
AB  - OBJECTIVES: Hereditary haemochromatosis is a disease that affects iron metabolism
      and leads to iron overload. Homozygosity for the H63D mutation is associated with
      increased transferrin saturation (TS) and ferritin levels. Our objective was to
      find out if the homozygosity of H63D mutation was the primary cause of iron
      overload. PATIENTS AND METHODS: We studied 45 H63D homozygotes (31 males and 14
      females) with biochemical iron overload and/or clinical features of
      haemochromatosis. The simultaneous detection of 18 known HFE, TFR2 and FPN1
      mutations and sequencing of the HAMP gene were performed to rule out the possible
      existence of genetic modifier factors related with iron overload. RESULTS: Values
      of biochemical iron overload, measured as percentage TS and serum ferritin
      concentration (SF), in our H63D homozygotes were significantly higher in patients
      than in controls: TS 55 +/- 15% vs. 35 +/- 15% and SF 764 (645-883) microg/L vs.
      115 (108-123) microg/L for patients and controls, respectively. These H63D
      homozygotes presented extreme hyperferritinaemia and no additional mutations in
      HFE, TFR2, FPN1 and HAMP genes were detected. CONCLUSIONS: The lack of additional
      mutations in our H63D homozygotes suggests that this genotype could be the
      primary cause of iron overload in these patients. Despite our results, we cannot
      entirely discount the possibility that one or more genetic modifier factor
      exists, simply because we were unable to find it, although there was a precedent
      in the HFE gene. Genetic modifier factors have been described for C282Y mutations
      in the HFE gene, but at the present time they have never been reported in H63D
      homozygotes.

PMID- 17042773
TI  - Low tolerance and high toxicity of thalidomide as maintenance therapy after
      double autologous stem cell transplant in multiple myeloma patients.
AB  - Although a double autologous peripheral blood stem cell transplant (APBSCT) is an
      effective therapy for patients (pts) with multiple myeloma and extends
      progression-free survival and overall survival, pts show a continued pattern of
      recurrent disease. The feasibility and tolerability of thalidomide (Thal)
      administered in the post-transplantation period as maintenance therapy was tested
      in 17 pts at a dose of 100 mg/d starting between 3 and 5 months after the second
      transplantation and continuing either until toxicity precluded further therapy or
      until pts had disease progression. After a median administration of 13 months
      (range: 3-26), 76.5% (13 pts) failed to tolerate Thal because of: transiet
      ischemic attack (three pts), severe fatigue (two), neutropenia (one),
      piastrinopenia (one), severe opportunistic infectious (two), erectile impotence
      (one), gastrointestinal toxicity (anorexia with weight loss one), peripheral
      neuropathy (two). After a median follow-up of 36 months (range: 10-59) from the
      second transplant, 13 patients attained a CR + near CR (with a conversion rate
      from 47.1% to 76.5%). In conclusion, Thal as maintenance therapy after double
      ASCT is associated with low feasibility and high toxicity and could prevent a
      lengthy use of this antineoplastic agent.

PMID- 17042774
TI  - Peripheral blood haematopoietic progenitor cells in patients with beta
      thalassaemia major receiving desferrioxamine or deferiprone as chelation therapy.
AB  - OBJECTIVES: The main adverse effect of deferiprone is the development of
      neutropenia, which occurs via an unknown mechanism. We aimed to gain insight into
      the pathogenesis of deferiprone-induced neutropenia by assessing the peripheral
      blood haematopoietic progenitor cells. METHODS: Sixteen patients with beta
      thalassaemia were studied; nine (Group A) were receiving desferrioxamine and
      seven (Group B) deferiprone. Ten healthy individuals comprised the control group
      (Group C). RESULTS: Granulocyte-erythrocyte-monocyte-megakaryocyte colony forming
      units were significantly more in Groups A and B compared with Group C.
      Granulocyte-macrophage colony forming units (CFU-GM) were significantly more in
      Group B compared with Group C. Macrophage colony forming units were significantly
      less in Group B compared with Group C. Granulocyte colony forming units (CFU-G)
      were significantly more in Group A compared with Group C. We found a trend in the
      difference in the number of CFU-G between patients' groups (P = 0.123). Adding
      serum from patients receiving deferiprone to cultures of controls resulted in a
      maturation arrest of the granulocytic lineage. CONCLUSION: Our findings point to
      a maturation arrest at the level of CFU-GM as a potential mechanism of
      deferiprone-induced neutropenia.

PMID- 17042775
TI  - Hepcidin--central regulator of iron metabolism.
AB  - The knowledge about mammalian iron metabolism has advanced dramatically over the
      past decades. Studies of genetics, biochemistry and molecular biology allowed us
      the identification and characterization of many of the molecules involved in
      regulation of iron homeostasis. Important progresses were made after the
      discovery in 2000 of a small peptide--hepcidin--that has been proved to play a
      central role in orchestration on iron metabolism also providing a link between
      iron metabolism and inflammation and innate immunity. Hepcidin directly interacts
      with ferroportin (FPN), the only known mammalian iron exporter, which is
      expressed by enterocytes, macrophages and hepatocytes. The direct hepcidin-FPN
      interaction allows an adaptative response from the body in situations that alter
      normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and
      inflammation).

PMID- 17042776
TI  - Meta-analysis: Alvimopan vs. placebo in the treatment of post-operative ileus.
AB  - BACKGROUND: Alvimopan is a selective, competitive mu-opioid receptor antagonist
      with limited oral bioavailability which may be used to reduce length of post
      operative ileus. AIM: The study compared alvimopan with placebo following bowel
      resection or total abdominal hysterectomy. METHODS: A meta-analysis of randomized
      controlled trials published between 2001 and 2006 of alvimopan vs. placebo was
      performed. The primary efficacy end-points were composite measures of passage of
      flatus, stool, and tolerance of solid food (GI-3) and passage of stool and
      tolerance of solid food (GI-2). The incidence of treatment emergent adverse
      events was assessed. RESULTS: Five trials matched the selection criteria,
      reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%)
      placebo. GI-3 significantly improved (hazard ratio 1.30; 95% confidence intervals
      1.16, 1.45, P < 0.001), as did GI-2 (hazard ratio 1.61; 95% confidence intervals
      1.26, 2.05, P < 0.001) on alvimopan 12 mg. Time to discharge (hazard ratio 1.26;
      95% confidence intervals 1.13, 1.40, P < 0.001), time to bowel motion (hazard
      ratio 1.74; 95% confidence intervals 1.29, 2.35, P < 0.001), and time to solid
      food (hazard ratio 1.14; 95% confidence intervals 1.01, 1.30, P < 0.04) also
      improved significantly. No difference was noted in the incidence of treatment
      emergent adverse events. CONCLUSIONS: Alvimopan showed significant advantages
      over placebo in restoring gastro-intestinal function, and reduced time to
      discharge following major abdominal surgery, with acceptable side effects.

PMID- 17042777
TI  - Chronic unremitting urticaria: is the use of antihistamines above the licensed
      dose effective? A preliminary study of cetirizine at licensed and above-licensed
      doses.
AB  - Recently, several authors have suggested an off-label increase of antihistamine
      dosage should be given to patients with chronic urticaria (CU) not responding to
      the usual, recommended doses, in order to gain better control of the disease.
      However, this recommendation is not evidence-based. The objective of this study
      was to assess the effectiveness of increased doses of antihistamines in patients
      with CU showing poor control at recommended doses. In total, 22 adult patients
      with moderate/severe CU not controlled with the usual antihistamine doses were
      studied. These subjects recorded urticaria severity on a visual analogue scale
      (range 0-10) for 2 weeks. During the first week, they were treated with
      cetirizine at the licensed dose (10 mg/day), and with a three-fold increased dose
      (10 mg x 3/day) during week 2. Only 1 patient (5%) responded satisfactorily to
      the increased dosage of antihistamine; in the remaining 21 subjects, urticaria
      scores did not change, and these patients had to be treated with steroids,
      ciclosporin, and in 1 case with cyclophosphamide. Disease control was eventually
      gained in all cases. This study suggests that the proportion of patients with
      severe CU that may gain a better control of their disease with high, off-label
      doses of antihistamines is probably small, and that most patients will eventually
      have to undergo more aggressive treatments.

PMID- 17042778
TI  - Functional characterization and Me ion specificity of a Ca-citrate transporter
      from Enterococcus faecalis.
AB  - Secondary transporters of the bacterial CitMHS family transport citrate in
      complex with a metal ion. Different members of the family are specific for the
      metal ion in the complex and have been shown to transport Mg(2+)-citrate, Ca(2+)
      citrate or Fe(3+)-citrate. The Fe(3+)-citrate transporter of Streptococcus mutans
      clusters on the phylogenetic tree on a separate branch with a group of
      transporters found in the phylum Firmicutes which are believed to be involved in
      anaerobic citrate degradation. We have cloned and characterized the transporter
      from Enterococcus faecalis EfCitH in this cluster. The gene was functionally
      expressed in Escherichia coli and studied using right-side-out membrane vesicles.
      The transporter catalyzes proton-motive-force-driven uptake of the Ca(2+)-citrate
      complex with an affinity constant of 3.5 microm. Homologous exchange is catalyzed
      with a higher efficiency than efflux down a concentration gradient. Analysis of
      the metal ion specificity of EfCitH activity in right-side-out membrane vesicles
      revealed a specificity that was highly similar to that of the Bacillus subtilis
      Ca(2+)-citrate transporter in the same family. In spite of the high sequence
      identity with the S. mutans Fe(3+)-citrate transporter, no transport activity
      with Fe(3+) (or Fe(2+)) could be detected. The transporter of E. faecalis
      catalyzes translocation of citrate in complex with Ca(2+), Sr(2+), Mn(2+), Cd(2+)
      and Pb(2+) and not with Mg(2+), Zn(2+), Ni(2+) and Co(2+). The specificity
      appears to correlate with the size of the metal ion in the complex.

PMID- 17042779
TI  - Saccharomyces cerevisiae alpha1,6-mannosyltransferase has a catalytic potential
      to transfer a second mannose molecule.
AB  - In yeast, the N-linked oligosaccharide modification in the Golgi apparatus is
      initiated by alpha1,6-mannosyltransferase (encoded by the OCH1 gene) with the
      addition of mannose to the Man(8)GlcNAc(2) or Man(9)GlcNAc(2) endoplasmic
      reticulum intermediates. In order to characterize its enzymatic properties, the
      soluble form of the recombinant Och1p was expressed in the methylotrophic yeast
      Pichia pastoris as a secreted protein, after truncation of its transmembrane
      region and fusion with myc and histidine tags at the C-terminus, and purified
      using a metal chelating column. The enzymatic reaction was performed using
      various kinds of pyridylaminated (PA) sugar chains as acceptor, and the products
      were separated by high performance liquid chromatography. The recombinant Och1p
      efficiently transferred a mannose to Man(8)GlcNAc(2)-PA and Man(9)GlcNAc(2)-PA
      acceptors, while Man(5)GlcNAc(2)-PA, which completely lacks alpha1,2-linked
      mannose residues, was not used as an acceptor. At high enzyme concentrations, a
      novel product was detected by HPLC. Analysis of the product revealed that a
      second mannose was attached at the 6-O-position of alpha1,3-linked mannose
      branching from the alpha1,6-linked mannose that is attached to beta1,4-linked
      mannose of Man(10)GlcNAc(2)-PA produced by the original activity of Och1p. Our
      results indicate that Och1p has the potential to transfer two mannoses from GDP
      mannose, and strictly recognizes the overall structure of high mannose type
      oligosaccharide.

PMID- 17042780
TI  - Diversity of human U2AF splicing factors.
AB  - U2 snRNP auxiliary factor (U2AF) is an essential heterodimeric splicing factor
      composed of two subunits, U2AF(65) and U2AF(35). During the past few years, a
      number of proteins related to both U2AF(65) and U2AF(35) have been discovered.
      Here, we review the conserved structural features that characterize the U2AF
      protein families and their evolutionary emergence. We perform a comprehensive
      database search designed to identify U2AF protein isoforms produced by
      alternative splicing, and we discuss the potential implications of U2AF protein
      diversity for splicing regulation.

PMID- 17042781
TI  - Characterization of novel M-superfamily conotoxins with new disulfide linkage.
AB  - The M-superfamily with the typical Cys framework (-CC-C-C-CC-) is one of the
      seven major superfamilies of conotoxins found in the venom of cone snails. Based
      on the number of residues in the last Cys loop (between C4 and C5), M-superfamily
      conotoxins can be provisionally categorized into four branches (M-1, M-2, M-3, M
      4) [Corpuz GP, Jacobsen RB, Jimenez EC, Watkins M, Walker C, Colledge C, Garrett
      JE, McDougal O, Li W, Gray WR, et al. (2005) Biochemistry44, 8176-8186]. Here we
      report the purification of seven M-superfamily conotoxins from Conus marmoreus
      (five are novel and two are known as mr3a and mr3b) and one known M-1 toxin tx3a
      from Conus textile. In addition, six novel cDNA sequences of M-superfamily
      conotoxins have been identified from C. marmoreus, Conus leopardus and Conus
      quercinus. Most of the above novel conotoxins belong to M-1 and M-2 and only one
      to M-3. The disulfide analyses of two M-1 conotoxins, mr3e and tx3a, revealed
      that they possess a new disulfide bond arrangement (C1-C5, C2-C4, C3-C6) which is
      different from those of the M-4 branch (C1-C4, C2-C5, C3-C6) and M-2 branch (C1
      C6, C2-C4, C3-C5). This newly characterized disulfide connectivity was confirmed
      by comparing the HPLC profiles of native mr3e and its two regioselectively folded
      isoforms. This is the first report of three different patterns of disulfide
      connectivity in conotoxins with the same cysteine framework.

PMID- 17042782
TI  - Binding areas of urokinase-type plasminogen activator-plasminogen activator
      inhibitor-1 complex for endocytosis receptors of the low-density lipoprotein
      receptor family, determined by site-directed mutagenesis.
AB  - Some endocytosis receptors related to the low-density lipoprotein receptor,
      including low-density lipoprotein receptor-related protein-1A, very-low-density
      lipoprotein receptor, and sorting protein-related receptor, bind protease
      inhibitor complexes, including urokinase-type plasminogen activator (uPA),
      plasminogen activator inhibitor-1 (PAI-1), and the uPA-PAI-1 complex. The unique
      capacity of these receptors for high-affinity binding of many structurally
      unrelated ligands renders mapping of receptor-binding surfaces of serpin and
      serine protease ligands a special challenge. We have mapped the receptor-binding
      area of the uPA-PAI-1 complex by site-directed mutagenesis. Substitution of a
      cluster of basic residues near the 37-loop and 60-loop of uPA reduced the
      receptor-binding affinity of the uPA-PAI-1 complex approximately twofold.
      Deletion of the N-terminal growth factor domain of uPA reduced the affinity 2-4
      fold, depending on the receptor, and deletion of both the growth factor domain
      and the kringle reduced the affinity sevenfold. The binding affinity of the uPA
      PAI-1 complex to the receptors was greatly reduced by substitution of basic and
      hydrophobic residues in alpha-helix D and alpha-helix E of PAI-1. The
      localization of the implicated residues in the 3D structures of uPA and PAI-1
      shows that they form a continuous receptor-binding area spanning the serpin as
      well as the A-chain and the serine protease domain of uPA. Our results suggest
      that the 10-100-fold higher affinity of the uPA-PAI-1 complex compared with the
      free components depends on the bonus effect of bringing the binding areas on uPA
      and PAI-1 together on the same binding entity.

PMID- 17042783
TI  - Odorant binding protein has the biochemical properties of a scavenger for 4
      hydroxy-2-nonenal in mammalian nasal mucosa.
AB  - Odorant binding proteins (OBP) are soluble lipocalins produced in large amounts
      in the nasal mucosa of several mammalian species. Although OBPs can bind a large
      variety of odorous compounds, direct and exclusive involvement of these proteins
      in olfactory perception has not been clearly demonstrated. This study
      investigated the binding properties and chemical resistance of OBP to the
      chemically reactive lipid peroxidation end-product 4-hydroxy-2-nonenal (HNE), in
      an attempt to establish a functional relationship between this protein and the
      molecular mechanisms combating free radical cellular damage. Experiments were
      carried out on recombinant porcine and bovine OBPs and results showed that both
      forms were able to bind HNE with affinities comparable with those of typical OBP
      ligands (K(d) = 4.9 and 9.0 microm for porcine and bovine OBP, respectively).
      Furthermore, OBP functionality, as determined by measuring the binding of the
      fluorescent ligand 1-aminoanthracene, was partially lost only when incubating HNE
      levels and exposure time to HNE exceeded physiological values in nasal mucosa.
      Finally, preliminary experiments in a simplified model resembling nasal
      epithelium showed that extracellular OBP can preserve the viability of an
      epithelial cell line derived from bovine turbinates exposed to toxic amounts of
      the aldehyde. These results suggest that OBP, which is expressed at millimolar
      levels, might reduce HNE toxicity by removing from the nasal mucus a significant
      fraction of the aldehyde that is produced as a consequence of direct exposure to
      the oxygen present in inhaled air.

PMID- 17042784
TI  - The MprF protein is required for lysinylation of phospholipids in listerial
      membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on
      Listeria monocytogenes.
AB  - Pathogenic bacteria have to cope with defence mechanisms mediated by adaptive and
      innate immunity of the host cells. Cationic antimicrobial peptides (CAMPs)
      represent one of the most effective components of the host innate immune
      response. Here we establish the function of Lmo1695, a member of the VirR
      dependent virulence regulon, recently identified in Listeria monocytogenes.
      Lmo1695 encodes a membrane protein of 98 kDa with strong homology to the multiple
      peptide resistance factor (MprF) of Staphylococcus aureus. Like staphylococcal
      MprF, we found that Lmo1695 is involved in the synthesis of the membrane
      phospholipid lysylphosphatidylglycerol (L-PG). In addition, Lmo1695 is also
      essential for lysinylation of diphosphatidylglycerol (DPG), another phospholipid
      widely distributed in bacterial membranes. A Deltalmo1695 mutant lacking the
      lysinylated phospholipids was particularly susceptible to CAMPs of human and
      bacterial origin. The mutant strain infected both epithelial cells and
      macrophages only poorly and was attenuated for virulence when tested in a mouse
      model of infection. Lmo1695 is a member of a growing list of survival factors
      which enable growth of L. monocytogenes in different environments.

PMID- 17042785
TI  - The exceptionally tight affinity of DnaA for ATP/ADP requires a unique aspartic
      acid residue in the AAA+ sensor 1 motif.
AB  - Escherichia coli DnaA, an AAA+ superfamily protein, initiates chromosomal
      replication in an ATP-binding-dependent manner. Although DnaA has conserved
      Walker A/B motifs, it binds adenine nucleotides 10- to 100-fold more tightly than
      do many other AAA+ proteins. This study shows that the DnaA Asp-269 residue,
      located in the sensor 1 motif, plays a specific role in supporting high-affinity
      ATP/ADP binding. The affinity of the DnaA D269A mutant for ATP/ADP is at least 10
      to 100-fold reduced compared with that of the wild-type and DnaA R270A proteins.
      In contrast, the abilities of DnaA D269A to bind a typical DnaA box, unwind oriC
      duplex in the presence of elevated concentrations of ATP, load DnaB onto DNA and
      support minichromosomal replication in a reconstituted system are retained.
      Whereas the acidic Asp residue is highly conserved among eubacterial DnaA
      homologues, the corresponding residue in many other AAA+ proteins is Asn/Thr and
      in some AAA+ proteins these neutral residues are essential for ATP hydrolysis but
      not ATP binding. As the intrinsic ATPase activity of DnaA is extremely weak, this
      study reveals a novel and specific function for the sensor 1 motif in tight
      ATP/ADP binding, one that depends on the alternate key residue Asp.

PMID- 17042786
TI  - Lex marks the spot: the virulent side of SOS and a closer look at the LexA
      regulon.
AB  - The SOS response that responds to DNA damage induces many genes that are under
      LexA repression. A detailed examination of LexA regulons using genome-wide
      techniques has recently been undertaken in both Escherichia coli and Bacillus
      subtilis. These extensive and elegant studies have now charted the extent of the
      LexA regulons, uncovered many new genes, and exposed a limited overlap in the
      LexA regulon between the two bacteria. As more bacterial genomes are analysed,
      more curiosities in LexA regulons arise. Several notable examples include the
      discovery of a LexA-like protein, HdiR, in Lactococcus lactis, organisms with two
      lexA genes, and small DNA damage-inducible cassettes under LexA control. In the
      cyanobacterium Synechocystis, genetic and microarray studies demonstrated that a
      LexA paralogue exerts control over an entirely different set of carbon-controlled
      genes and is crucial to cells facing carbon starvation. An examination of SOS
      induction evoked by common therapeutic drugs has shed new light on unsuspected
      consequences of drug exposure. Certain antibiotics, most notably fluoroquinolones
      such as ciprofloxacin, can induce an SOS response and can modulate the spread of
      virulence factors and drug resistance. SOS induction by beta-lactams in E. coli
      triggers a novel form of antibiotic defence that involves cell wall stress and
      signal transduction by the DpiAB two-component system. In this review, we provide
      an overview of these new directions in SOS and LexA research with emphasis on a
      few themes: identification of genes under LexA control, the identification of new
      endogenous triggers, and antibiotic-induced SOS response and its consequences.

PMID- 17042787
TI  - Specificity of Streptococcus pyogenes NAD(+) glycohydrolase in cytolysin-mediated
      translocation.
AB  - The mechanism by which the cytolysin-mediated translocation (CMT) pathway of the
      Gram-positive pathogen Streptococcus pyogenes injects effector proteins into the
      cytosol of an infected host cell via the pore-forming protein streptolysin O is
      unknown. Key questions include whether the pathway can discriminate between
      different substrates for translocation, and whether the effector protein plays an
      active or passive role in the translocation process. Here we show that CMT can
      discriminate between a known effector of the pathway, the S. pyogenes NAD(+)
      glycohydrolase (SPN), and a second secreted protein, the mitogenic factor (MF),
      routing the former into the host cell cytosol and the latter into the
      extracellular milieu. Residues within the amino-terminal 190 residues of SPN were
      essential for discrimination, as deletions within this domain produced proteins
      that retained full enzymatic activity, but were completely uncoupled from the
      translocation pathway. The enzymatic domain itself played a pivotal role in the
      discrimination as deletions within this domain also produced translocation
      incompetent proteins and the conversion of MF to a translocation-competent form
      required fusion with both SPN domains in a contiguous orientation. These data
      establish that CMT is discriminatory, and that SPN is a multidomain protein that
      plays an active role in its translocation.

PMID- 17042788
TI  - Topoisomerases of kinetoplastid parasites: why so fascinating?
AB  - DNA topoisomerases are the key enzymes involved in carrying out high precision
      DNA transactions inside the cells. However, they are detrimental to the cell when
      a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by
      trapping the enzymes in covalent complexes on the DNA. The discovery of unusual
      heterodimeric topoisomerase I in kinetoplastid family added a new twist in
      topoisomerase research related to evolution, functional conservation and their
      preferential sensitivity to Camptothecin. On the other hand, structural and
      mechanistic studies on kinetoplastid topoisomerase II delineate some
      distinguishing features that differentiate the parasitic enzyme from its
      prokaryotic and eukaryotic counterparts. This review summarizes the recent
      advances in research in kinetoplastid topoisomerases, their evolutionary
      significance and the death of the unicellular parasite Leishmania donovani
      induced by topoisomerase I inhibitor camptothecin.

PMID- 17042789
TI  - Differential disinhibition of the neonatal hypothalamic- pituitary-adrenal axis
      in brain-specific CRH receptor 1-knockout mice.
AB  - In the adult, corticotropin-releasing hormone (CRH) is the key mediator for the
      behavioural and neuroendocrine response to stress. It has also been hypothesized
      that, during postnatal development of the stress system, CRH controls the
      activity of the HPA axis and mediates the effects of early disturbances, e.g. 24
      h of maternal deprivation. In the current study we investigated the function of
      specific brain corticotropin-releasing hormone receptor type 1 (CRHR1)
      subpopulations in the control of the HPA axis during postnatal development under
      basal conditions as well as after 24 h of maternal deprivation. We used two
      conditional CRHR1-deficient mouse lines which lack this receptor, either
      specifically in forebrain and limbic structures (Cam-CRHR1) or in all neurons
      (Nes-CRHR1). Basal circulating corticosterone was increased in Nes-CRHR1 mice
      compared to controls. Corticosterone response to maternal deprivation was
      significantly increased in both CRHR1-deficient lines. In the paraventricular
      nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin
      expression levels. In contrast, gene expression in Nes-CRHR1 pups was strikingly
      similar to that in maternally deprived control pups. Furthermore, maternal
      deprivation resulted in an enhanced response of Cam-CRHR1 pups in the brain,
      while expression levels in Nes-CRHR1 mouse pups were mostly unchanged. Our
      results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the
      suppression of basal corticosterone secretion in the neonate, while limbic and/or
      forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by
      maternal deprivation.

PMID- 17042790
TI  - Preferential responses in amygdala and insula during presentation of facial
      contempt and disgust.
AB  - Some authors consider contempt to be a basic emotion while others consider it a
      variant of disgust. The neural correlates of contempt have not so far been
      specifically contrasted with disgust. Using functional magnetic resonance imaging
      (fMRI), we investigated the neural networks involved in the processing of facial
      contempt and disgust in 24 healthy subjects. Facial recognition of contempt was
      lower than that of disgust and of neutral faces. The imaging data indicated
      significant activity in the amygdala and in globus pallidus and putamen during
      processing of contemptuous faces. Bilateral insula and caudate nuclei and left as
      well as right inferior frontal gyrus were engaged during processing of disgusted
      faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly
      different activations in the amygdala. On the other hand, disgusted faces
      elicited greater activation than contemptuous faces in the right insula and
      caudate. Our findings suggest preferential involvement of different neural
      substrates in the processing of facial emotional expressions of contempt and
      disgust.

PMID- 17042791
TI  - Depolarization-induced suppression of inhibition mediated by endocannabinoids at
      synapses from fast-spiking interneurons to medium spiny neurons in the striatum.
AB  - Endogenous cannabinoids (endocannabinoids) act as retrograde inhibitory
      messengers in various regions of the brain. We have recently reported that
      endocannabinoids mediate short-term retrograde suppression of excitatory synaptic
      transmission from the neocortex to medium spiny (MS) neurons, the major
      projection neurons from the striatum. However, it remains unclear whether
      endocannabinoids modulate inhibitory transmission in the striatum. Here we show
      that depolarization of MS neurons induces transient suppression of inhibition
      that is mediated by retrograde endocannabinoid signalling. By paired recording
      from a fast-spiking (FS) interneuron and an MS neuron, we demonstrated that FS-MS
      inhibitory synapses undergo endocannabinoid-mediated retrograde suppression. We
      verified that GABAergic inhibitory terminals immunopositive for parvalbumin (PV),
      a marker for FS interneurons, expressed CB1 receptors. These PV-CB1 double
      positive terminals surrounded dopamine D1 receptor-positive and D2 receptor
      positive MS neurons; these constitute direct and indirect pathways, respectively.
      These results suggest that endocannabinoid-mediated retrograde suppression of
      inhibition influences information flow along both direct and indirect pathways,
      depending on the activity of MS neurons.

PMID- 17042792
TI  - Bottom-up, not top-down, modulation of imitation by human and robotic models.
AB  - Visual observation of human actions provokes more motor activation than
      observation of robotic actions. We investigated the extent to which this
      visuomotor priming effect is mediated by bottom-up or top-down processing. The
      bottom-up hypothesis suggests that robotic movements are less effective in
      activating the 'mirror system' via pathways from visual areas via the superior
      temporal sulcus to parietal and premotor cortices. The top-down hypothesis
      postulates that beliefs about the animacy of a movement stimulus modulate mirror
      system activity via descending pathways from areas such as the temporal pole and
      prefrontal cortex. In an automatic imitation task, subjects performed a
      prespecified movement (e.g. hand opening) on presentation of a human or robotic
      hand making a compatible (opening) or incompatible (closing) movement. The speed
      of responding on compatible trials, compared with incompatible trials, indexed
      visuomotor priming. In the first experiment, robotic stimuli were constructed by
      adding a metal and wire 'wrist' to a human hand. Questionnaire data indicated
      that subjects believed these movements to be less animate than those of the human
      stimuli but the visuomotor priming effects of the human and robotic stimuli did
      not differ. In the second experiment, when the robotic stimuli were more angular
      and symmetrical than the human stimuli, human movements elicited more visuomotor
      priming than the robotic movements. However, the subjects' beliefs about the
      animacy of the stimuli did not affect their performance. These results suggest
      that bottom-up processing is primarily responsible for the visuomotor priming
      advantage of human stimuli.

PMID- 17042793
TI  - A distinct anatomical network of cortical areas for analysis of motion in far
      peripheral vision.
AB  - We defined cortical areas involved in the analysis of motion in the far
      peripheral visual field, a poorly understood aspect of visual processing in
      primates. This was accomplished by small tracer injections within and around the
      representations of the monocular field of vision ('temporal crescents') in the
      middle temporal area (MT) of marmoset monkeys. Quantitative analyses demonstrate
      that the representation of the far periphery receives specific connections from
      the retrosplenial cortex (areas 23v and prostriata), as well as comparatively
      stronger inputs from the primary visual area (V1) and from areas surrounding MT
      (in particular, the medial superior temporal area, MST). In contrast, the far
      peripheral representation receives little or no input from most other
      extrastriate areas, including the second visual area (V2), the densely myelinated
      areas of the dorsomedial cortex, and ventral stream areas; these areas are shown
      to have robust projections to other parts of MT. Our results demonstrate that the
      responses of cells in different parts of a same visual area can be determined by
      different combinations of synaptic inputs, in terms of areas of origin. They also
      suggest that the interconnections responsible for motion processing in the far
      periphery of the visual field convey information that is crucial for rapid
      response aspects of visual function such as orienting, postural and defensive
      reactions.

PMID- 17042794
TI  - Zinc neurotoxicity is dependent on intracellular NAD levels and the sirtuin
      pathway.
AB  - Zinc neurotoxicity has been demonstrated in ischemic, seizure, hypoglycemic, and
      trauma-induced neuronal death where Zn(2+) is thought to be synaptically released
      and taken up in neighbouring neurons, reaching toxic concentrations. We
      previously demonstrated that toxicity of extracellular Zn(2+) depended on entry,
      elevation in intracellular free Zn(2+) ([Zn(2+)](i)), a reduction in NAD(+) and
      ATP levels, and dysfunction of glycolysis and cellular metabolism. We suggested
      that PARP-1 activation alone can not explain this loss of neuronal NAD(+). NAD(+)
      was recently demonstrated to permeate neurons and glia, and we have now shown
      that exogenous NAD(+) can reduce Zn(2+) neurotoxicity, and 3-acetylpyridine,
      which generates inactive NAD(+), potentiated Zn(2+) neurotoxicity. Sirtinol and 2
      hydroxynaphthaldehyde, inhibitors of the sirtuin pathway (SIRT proteins are
      NAD(+)-catabolic protein deacetylases), attenuated both acute and chronic Zn(2+)
      neurotoxicity. Resveratrol and fisetin (sirtuin activators) potentiated NAD(+)
      loss and Zn(2+) neurotoxicities. Furthermore, neuronal cultures derived from the
      Wld(s) mouse, which overexpress the NAD(+) synthetic enzyme nicotinamide
      mononucleotide adenyl transferase (NMNAT-1), had reduced sensitivity to Zn(2+)
      neurotoxicity. Finally, nicotinamide was demonstrated to attenuate CA1 neuronal
      death after 10 min of global ischemia in rat even if administered 1 h after the
      insult. Together with previous data, these results further implicate NAD(+)
      levels in Zn(2+) neurotoxicity.

PMID- 17042795
TI  - An in vivo analysis of Schwann cell programmed cell death in embryonic mice: the
      role of axons, glial growth factor, and the pro-apoptotic gene Bax.
AB  - Building upon previous in vitro studies, the present investigation involves an in
      vivo examination of Schwann cell programmed cell death (PCD) and development in
      the brachial spinal ventral roots of embryonic mice. The period of Schwann cell
      PCD was found to occur between embryonic days (E) 11.5 and 18.5, which is in
      close coincidence with the PCD period of associated brachial motoneurons (E13.5
      E18.5). Additionally, Schwann cells exhibited a peak in proliferation at E11.5,
      and differentiation from the precursor to the immature Schwann cell stage between
      E12.5 and E14.5. Axon-mediated Schwann cell survival was demonstrated in vivo by
      excitotoxic elimination of motoneurons and their axons, via NMDA treatment in
      utero. This treatment increased apoptotic Schwann cell death within degenerating
      ventral roots. Conversely, in utero co-treatment of glial growth factor (GGF)
      with NMDA resulted in decreased Schwann cell death, a finding which supports
      previous reports of the promotion of Schwann cell survival by GGF. Analysis of
      mice lacking Bax, a pro-apoptotic Bcl-2 protein, revealed that Schwann cell PCD
      occurred independently of Bax. However, owing to the lack of motoneuron PCD in
      Bax-knockout mice, and the corresponding increase in the number of ventral root
      axons, a decrease in Schwann cell PCD was observed during the normal period of
      motoneuron PCD. In conclusion, our findings regarding the regulation of Schwann
      cell development in vivo are consistent with the conclusions from in vitro
      studies, including a dependency on axons for survival and proliferation signals,
      timing of differentiation, and a dependency on GGF.

PMID- 17042796
TI  - Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic
      nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model.
AB  - The pedunculopontine nucleus (PPN) and the subthalamic nucleus (STN) are
      reciprocally connected by excitatory projections. In the 6-hydroxydopamine (6
      OHDA) rat model the PPN was found to be hyperactive. Similarly, the STN and the
      substantia nigra pars reticulata (SNr) showed increased activity in Parkinson's
      disease (PD) animal models. A lesion of the STN was shown to restore increased
      activity levels in the SNr of 6-OHDA-treated rats. As the STN and the PPN were
      reciprocally connected by excitatory projections and both structures were shown
      to be hyperactive in PD animal models, the present study was performed in order
      to investigate the changes in neuronal activity of the STN and SNr under urethane
      anesthesia after unilateral ibotenic acid lesioning of the PPN in animals with
      previous unilateral 6-OHDA lesions of the substantia nigra pars compacta (SNc).
      The firing rate of STN neurons significantly increased from 10.3 +/- 0.6 spikes/s
      (mean +/- SEM) to 17.8 +/- 1.8 spikes/s after SNc lesion and returned to normal
      levels of 10.8 +/- 0.7 spikes/s after additional lesion of the PPN. Similarly,
      the firing rate of SNr neurons significantly increased from 19.0 +/- 1.1 to 25.9
      +/- 1.4 spikes/s after SNc lesion, the hyperactivity being reversed after
      additional PPN lesion to 16.8 +/- 1.2 spikes/s. The reversal of STN and SNr
      hyperactivity of 6-OHDA-treated rats by additional PPN lesion suggests an
      important modulatory influence of the PPN on STN activity. Moreover, these
      findings could indicate a new therapeutic strategy in PD by interventional
      modulation of the PPN.

PMID- 17042797
TI  - Stereological methods reveal the robust size and stability of ectopic hilar
      granule cells after pilocarpine-induced status epilepticus in the adult rat.
AB  - Following status epilepticus in the rat, dentate granule cell neurogenesis
      increases greatly, and many of the new neurons appear to develop ectopically, in
      the hilar region of the hippocampal formation. It has been suggested that the
      ectopic hilar granule cells could contribute to the spontaneous seizures that
      ultimately develop after status epilepticus. However, the population has never
      been quantified, so it is unclear whether it is substantial enough to have a
      strong influence on epileptogenesis. To quantify this population, the total
      number of ectopic hilar granule cells was estimated using unbiased stereology at
      different times after pilocarpine-induced status epilepticus. The number of hilar
      neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated
      using the optical fractionator method. The results indicate that the size of the
      hilar ectopic granule cell population after status epilepticus is substantial,
      and stable over time. Interestingly, the size of the population appears to be
      correlated with the frequency of behavioral seizures, because animals with more
      ectopic granule cells in the hilus have more frequent behavioral seizures. The
      hilar ectopic granule cell population does not appear to vary systematically
      across the septotemporal axis, although it is associated with an increase in
      volume of the hilus. The results provide new insight into the potential role of
      ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.

PMID- 17042798
TI  - Early postnatal changes in respiratory activity in rat in vitro and modulatory
      effects of substance P.
AB  - Developmental changes in the respiratory activity and its modulation by substance
      P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from
      the day of birth to day 3 (P0-P3). The respiratory network activity in the
      ventrolateral medulla was represented by two types of bursts: basic regular
      bursts with typical decrementing shape and biphasic bursts appearing after
      augmented biphasic discharges in inspiratory neurons. With advancing postnatal
      age the respiratory output was considerably modified; the basic rhythm became
      faster by 20%, whereas the biphasic burst rate, which was originally 15 times
      slower, declined further by 180% and the C4 burst duration significantly
      decreased by 20% due to reduced decay time without preceding changes in the
      central inspiratory drive. SP had an age-dependent excitatory effect on
      respiratory activity. In the basic rhythm, SP could induce transient rhythm
      cessations on P0-P2 but not on P3. For the biphasic burst frequency, the
      sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP
      induced changes increased. In both types of bursts, SP prolonged C4 burst
      duration due to increasing decay time. This effect was three times greater on P3
      and did not depend on the central inspiratory drive. Our results suggest that the
      potency of SP to regulate the respiratory activity elevates during the early
      postnatal period. The developmental changes in the respiratory activity appear to
      represent the transient stage in the maturation of rhythm and pattern generation
      mechanisms facilitating adaptive behavior of a quickly growing organism.

PMID- 17042800
TI  - Quality of care, health system errors, and nurses.

PMID- 17042801
TI  - Safety in health care today: more than just freedom from errors and accidents?

PMID- 17042799
TI  - Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway
      inflammation in a murine model of asthma.
AB  - A number of epidemiological and clinical studies have suggested an inverse
      association between allergy and helminth infection, such as Schistosomiasis.
      Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of
      native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory
      activity, modulating airway inflammation and inhibiting asthma development. The
      frequency of CD4(+) CD25(+) T cells was determined by flow cytometry for mice
      treated with ovalbumin (OVA), CD25(+) depletion/OVA, schistosome egg antigens,
      schistosome egg antigens/OVA and for control mice. The ability of CD25(+) T cells
      from these mice to suppress T-cell proliferation and cytokine production was
      investigated both in vivo and in vitro. Results showed that the CD4(+) CD25(+) T
      cells of OVA-treated mice exhibited impaired control of dysregulated mucosal T
      helper 2 responses compared to the controls (P < 0.05). Depletion of CD25(+)
      cells accelerated OVA-induced airway inflammation and increased the expression of
      interleukin (IL)-5 and IL-4. Treatment with schistosome egg antigens increased
      the number and suppressive activity of CD4(+) CD25(+) T cells, which made IL-10,
      but little IL-4. In a murine model of asthma, S. japonicum egg antigens decreased
      the expression of Th2 cytokines, relieved antigen-induced airway inflammation,
      and inhibited asthma development. Thus, we provided evidence that S. japonicum
      egg antigens induced the production of CD4(+) CD25(+) T cells, resulting in
      constitutive immunosuppressive activity and inhibition of asthma development.
      These results reveal a novel form of protection against asthma and suggest a
      mechanistic explanation for the protective effect of helminth infection on the
      development of allergy.

PMID- 17042802
TI  - Recognizing and reporting child physical abuse: a survey of primary healthcare
      professionals.
AB  - AIM: This paper reports a study of the self-reported ability and behaviours of
      primary healthcare professionals in Northern Ireland to recognise child physical
      abuse. A secondary aim was to assess the educational and training needs of these
      professionals. BACKGROUND: In the United Kingdom, 7% of children suffer serious
      physical abuse by a parent or carer, and two children aged under 15 years die
      from abuse each week. Recognizing child physical abuse depends on the knowledge
      and skills of a variety of healthcare professionals. METHODS: A stratified random
      sample of 979 nurses, doctors, and dentists working in primary care in Northern
      Ireland were sent a postal questionnaire; 419 responded, giving a 43% response
      rate. The data were collected in 2002-2003. FINDINGS: In their working lives 60%
      (251) said that they had seen a suspicious child physical abuse case; however,
      only 47% (201) had reported a suspicious case to the authorities, leaving a 13%
      gap in reporting. Although 74% (310) of respondents were aware of some of the
      mechanisms for reporting child physical abuse, 79% (332) requested further
      education on this topic. Ability to recognize and willingness to report abuse
      cases discriminated between the three professional groups. Compared with doctors
      or dentists, community nurses were statistically significantly more likely to
      recognize and report suspicions of child physical abuse, and were the group most
      aware of child abuse issues and the most willing to become involved in abuse
      cases. CONCLUSIONS: The findings suggest that professional fears and anxieties
      and lack of knowledge act as barriers to recognizing and reporting abuse and that
      more specific education and support for primary care professionals is required.

PMID- 17042803
TI  - Care of patients with chronic obstructive pulmonary disease in primary health
      care.
AB  - AIM: This paper is a report of a study of nurses' perceptions of caring for
      patients with chronic obstructive pulmonary disease. BACKGROUND: Chronic
      obstructive pulmonary disease is a global health problem and the number of
      patients being treated with this disease in primary healthcare settings is
      increasing. This places new demands on the nurses involved. METHOD: A
      phenomenographic approach was adopted, using a purposive sample. Data were
      generated between February and May 2003 from 20 interviews with district nurses
      and general nurses who cared for patients in primary healthcare settings with
      chronic obstructive pulmonary disease. FINDINGS: In most cases, nurses cared for
      older people with moderate to severe chronic obstructive pulmonary disease. They
      described this care from two overall orientations: task and individual. The
      nurses' perceptions of the care of these patients were described as creating
      commitment and participation by establishing a good relationship with patients
      and supporting them in their personal care, educating patients by supplying
      information and knowledge in various ways, co-operation by co-operating with or
      referring to other caregivers, and arranging and implementing clinical
      examinations and treatments. CONCLUSION: The type of care depended on who the
      patient met: either a task-oriented nurse or an individual-oriented nurse.
      Therefore, nursing programmes should pay special attention to the support and
      guidance of new and inexperienced and task-oriented nurses. Healthcare planners
      should take into consideration the need for individualized care when organizing
      care and allocating resources for chronically ill people.

PMID- 17042804
TI  - Health preferences and decision-making needs of disadvantaged women.
AB  - AIM: This paper reports the results of a survey of disadvantaged women in La
      Pintana, a municipality of Santiago, Chile, to determine their health decision
      making needs. BACKGROUND: Research is needed as there is no published community
      based study focusing specifically on health decision-making needs of
      disadvantaged women. METHODS: From April to November 1999, we conducted a cross
      sectional interview survey of women registered at primary healthcare centres in
      La Pintana, an impoverished municipality of Santiago, Chile. RESULTS: The survey
      participants were 554 adult women over 15 years of age. Seventy-five percent
      reported making current health-related decisions. Types of decisions were
      primarily about navigation: where, when and from whom to seek care. The most
      common role in decision-making was sharing the decision with others, specifically
      husbands and other family members. Fifty-four percent experienced decisional
      conflict or uncertainty about options. Those reporting more manifestations of
      decisional conflict were more likely to lack information on available options,
      pros and cons of the options, and chances of benefits and harms associated with
      the options; they were also more likely to be unclear about what was important to
      them, to feel pressure from others, lack skill or ability in decision-making and
      be older. The most common strategies used when making all types of decisions were
      obtaining information on options and recommendations, and getting support from
      others. Participants preferred to receive information about options through
      counselling from their physicians, rather than nurses, from printed materials and
      from discussion groups of people facing the same decision. CONCLUSION: The
      majority of disadvantaged women were actively involved in decision-making and
      needed decision support to navigate the healthcare system. Nurses should play a
      more pivotal role in providing health decision support. This study needs to be
      replicated in other countries and cultural contexts.

PMID- 17042805
TI  - Living in the shadow of fear: adolescents' lived experience of depression.
AB  - AIM: This paper reports a phenomenological study whose aim was to gain an
      understanding of what it was like to be an adolescent living with depression.
      BACKGROUND: Depression is a significant mental health problem among adolescents.
      Identifying the meanings that adolescents assign to their experiences with
      depression is needed in order to develop interventions that will improve their
      care and quality of life. METHOD: The study took place in a city in Western
      Canada. Fourteen adolescents (13.5 to 18 years) diagnosed with depression
      participated in individual open-ended interviews and focus group interviews
      between July 2001 and June 2002. Field notes were recorded. Thematic statements
      that were representative of the adolescents' lived experience were isolated from
      the interviews and field notes. Using all the phrases, sentence clusters and
      field notes, the data were then reduced until essential and incidental themes
      emerged. FINDINGS: "Living in the shadow of fear" emerged as the essence of the
      adolescents' experiences and ultimately defined what it was like to live with
      depression. The shadow of fear was associated not only with fear of a return of
      the "bad" feelings related to their depression, but also to fear of not getting
      help, not surviving the "bad" feelings, and fear of having to do all the "hard
      work" in overcoming the "bad" feelings. This essence was supported by four
      themes: "containing the shadow of fear", "keeping the self alive", "maintaining a
      sense of belonging in the world" and "feeling valued as a human being".
      CONCLUSIONS: Adolescents with depression need adequate resources and support
      throughout the illness trajectory, including those periods when their depression
      is under control.

PMID- 17042806
TI  - Percutaneous endoscopic gastrostomies: the burden of treatment from a patient
      perspective.
AB  - AIM: This paper reports a study of patients' experiences of this relatively new
      technology, and explores possible strategies for defining, delineating and
      addressing patients' concerns, problems and needs. BACKGROUND: The number of
      patients in the community relying on percutaneous endoscopic gastrostomy for
      their nutritional needs is increasing, but percutaneous endoscopic gastrostomy
      feeding is not problem-free. However, few studies report on its impact from a
      patient perspective. METHODS: Twenty adults with long-term percutaneous
      endoscopic gastrostomies were interviewed in their own homes, using both semi
      structured and structured approaches. Qualitative data were analysed thematically
      and related to a symptom checklist and an established quality of life measure,
      the Short Form-12. FINDINGS: Most participants felt that insertion of a
      percutaneous endoscopic gastrostomy had been life-saving, but found that
      percutaneous endoscopic gastrostomy feeding came to dominate their lives and was
      associated with an appreciable "burden of treatment". Some, but not all, of the
      problems recounted were unavoidable: percutaneous endoscopic gastrostomy feeding
      inevitably imposed physical restrictions on mobility; 17/20 participants had
      experienced serious technical problems with their percutaneous endoscopic
      gastrostomy tubes. On structured questioning, all interviewees had some,
      potentially treatable, gastrointestinal symptoms, and eight had continuous
      problems. In some cases, the burden of treatment was exaggerated by being
      unanticipated and, for 13 patients, difficulties with care provided by non
      specialist services. Describing this "burden of treatment" for each patient
      required both a narrative and a structured approach: without the symptom
      checklists, some important and treatable problems were missed. Both physical and
      mental health Short Form-12 scores were low, and mental health scores were
      congruent with the interview data. CONCLUSIONS: It might be possible to reduce
      the "burden of treatment" identified by incorporating a structured approach to
      patient monitoring and by reviewing the occupational territories of specialist
      and non-specialist practitioners. Further research with larger numbers of
      participants is needed to explore the integration of narrative and quantitative
      data when determining patients' clinical needs.

PMID- 17042807
TI  - Factors contributing to frailty: literature review.
AB  - AIM: This paper presents a review of theoretical and research literature in order
      to identify the factors contributing to frailty. BACKGROUND: Frailty is a
      multifaceted gerontological concept that lacks a clear definition, but may result
      from an identifiable homogeneous cluster of bio-psycho-social-spiritual factors.
      METHOD: A total of 134 articles were identified through a search of the MEDLINE
      (1966 to July 2004), CINAHL (1982 to July 2004), PsychInfo (1985 to July 2004)
      and Ageline (1995 to July 2004) databases. Each article was reviewed to determine
      its fit with inclusion/exclusion criteria. Seven research and 11 theoretical
      articles were retained and further reviewed for methodological quality using a
      validity tool. FINDINGS: Seventeen different definitions of frailty were
      identified. Regardless of the differing definitions, common contributing factors
      could be identified. Physical, cognitive/psychological, nutritional and social
      factors, as well as ageing and disease, were evident in both the theoretical and
      research literature. CONCLUSIONS: Although there is strong agreement that a
      relationship exists between a cluster of factors and frailty, designation of the
      factors as contributors or outcomes of frailty differs. Without a clear
      explanatory theory of the path from contributors to frailty to outcomes, research
      will continue to produce confusing results. A theoretical framework that includes
      bio-psycho-social-spiritual factors as contributors to frailty is recommended as
      the most useful framework for gerontological nursing.

PMID- 17042808
TI  - Developing an advanced nurse practitioner service in emergency care: attitudes of
      nurses and doctors.
AB  - AIM: This paper reports a study to determine the attitudes of nurses, doctors and
      general medical practitioners towards the development of an advanced nurse
      practitioner service within an emergency department. BACKGROUND: The role of
      advanced nurse practitioner in emergency care has emerged in a number of
      countries, and has brought with it confusion about titles, role boundaries,
      clinical accountability and educational requirements. Initially, the role
      resulted from a need for healthcare professionals to provide a service to the
      increased numbers of patients presenting to hospital with less urgent problems.
      Since then, the service has evolved to one where nurse practitioners provide high
      quality and cost-effective care to persons who seek help for non-urgent, urgent
      or emergent conditions in a variety of emergency care settings. However, little
      research could be identified on the attitudes of relevant nursing and medical
      staff towards the development of this role. METHODS: A questionnaire survey was
      carried out, and a 29-item Likert rating scale was developed to measure
      attitudes. Along with some demographic variables, two open-ended questions were
      added to allow respondents to elaborate on what they perceived as benefits and
      difficulties associated with an advanced nurse practitioner service. All general
      practitioners, emergency nurses and emergency doctors in one health board in the
      Republic of Ireland were targeted, and 25 emergency nurses, 13 emergency doctors
      and 69 general practitioners were approached to take part. Data were collected in
      February 2004. FINDINGS: An overall response rate of 74.8% was achieved. All
      respondents were positive towards the development of an advanced nurse
      practitioner service, with general practitioners being less positive. The
      principal differences appeared between general practitioners and hospital
      emergency care staff. CONCLUSION: There is a need for a multidisciplinary
      approach to the planning of advanced nurse practitioner services. To achieve
      multiprofessional acceptance, an accredited and standardized education programme
      is required, and this must address existing role boundaries.

PMID- 17042809
TI  - Developing nursing and midwifery research capacity in a university department:
      case study.
AB  - AIM: This paper reports a case study which examined the selection, implementation
      and outcomes of one university department's approach to building research
      capacity in nursing and midwifery. BACKGROUND: The literature identifies building
      nursing research capacity as an important challenge. In countries such as
      Australia and the United Kingdom it is taking place in the context of the move of
      nurse education into the university sector. Structural and cultural barriers to
      building academic nursing research capacity exist. Previous studies highlight the
      strategies that academic departments adopt to build nursing research capacity.
      METHODS: Using case study methodology, data were collected using documentary
      analysis and semi-structured interviews with a purposive sample of 27 academic
      and related staff and a focus group with seven staff. The data were collected
      between 2003 and 2005. FINDINGS: The department had adopted an inclusive approach
      to capacity development (allowing all teaching staff to develop their research
      capability), but is now moving towards a more focused path and the cultivation of
      "leading edge" research. Neophyte researchers described lacking confidence in
      undertaking research, and expressed a need for more formal support structures.
      The importance of effective management of capacity building was highlighted,
      including transparent communication and mapping of existing capacity. Key
      external influences included the lack of core research funding, and divergence
      between the university's emphasis on research and the department's desire to
      develop an interface between teaching, research and clinical practice.
      CONCLUSION: Academic leadership and educational management should work in tandem.
      Staff development and the provision of time and support are crucial aspects of
      research capacity development. The effectiveness of "inclusive" and "exclusive"
      approaches to research capacity development depends on the nature of each
      department, and they are not mutually exclusive.

PMID- 17042810
TI  - A revision of a job evaluation system.
AB  - AIMS: This paper reports a revision of the United Kingdom's National Health
      Service Job Evaluation System and tests the revised system in eight clinical
      nursing management jobs in four Turkish hospitals. BACKGROUND: A job evaluation
      system was developed in the United Kingdom in 2003-2004. Most studies have
      focused on how the whole system will be implemented in a health organization. No
      study investigating proficiency of the system in terms of factors and their level
      definitions was found. METHODS: The factors Knowledge, Training and experience
      and Working conditions were divided into five factors: Knowledge, Experience,
      Education, Environmental conditions and Hazards. To test the revised system, all
      the nursing management jobs in four hospitals were evaluated using a factor-based
      questionnaire including nurses' demographic information and 19 variables. The
      questionnaire was distributed to 57 supervisor nurses in 31 clinics at four
      hospitals in one Turkish city in 2005. All the questionnaires were analysed to
      evaluate the jobs. RESULTS: The job scores change depending on clinical
      conditions. Although the score range in the National Health Service Job
      Evaluation system has been determined as 405-465 points (band VI) for Nurse team
      leader and 469-536 points (band VII) for Nurse team manager jobs, the job scores
      in the present study were 363 (band V) - 557 points (band VIIIa) and 379 (band V)
      - 586 points (band VIIIa) respectively. CONCLUSION: Although this exploratory
      study was limited to four hospitals in one city in Turkey, the results indicated
      that two new jobs would be identified in the National Health Service system to
      match the jobs in the intensive care and emergency units.

PMID- 17042811
TI  - Rules and resources: a structuration approach to understanding the coordination
      of children's inpatient health care.
AB  - AIM: This paper presents findings from a multi-method study exploring the process
      of care coordination in children's inpatient health care. BACKGROUND: Existing
      work on care coordination is typified by "black-box" type studies that measure
      inputs to and outcomes of care coordination roles and practices, without
      addressing the process of coordination. METHOD: Using questionnaires, interviews
      and observation to collect data in multiple sites in the United Kingdom and
      Denmark between 1999 and 2005, the study gathered the perceptions of staff and
      compared these with observed practice. Giddens' structuration theory was used to
      provide an analytical and explanatory framework. FINDINGS: Current care
      coordination practice is diverse and inconsistent. It involves a wide range of
      clinical and non-clinical staff, many of whom perceive a lack of clarity about
      who should perform specific coordination activities. Staff draw upon a wide range
      of different material and non-material resources in coordinating care, the use of
      which is governed by largely tacit and informal rules. CONCLUSIONS: Care
      coordination can be usefully conceptualized as a "structurated" process--one that
      is continually produced and reproduced by staff using rules and resources to
      "instantiate" or bring about care coordination through action. Potentially
      negative implications of this are manifested in diversity and inconsistency in
      care coordination practice. However, positive aspects such as the opportunity
      this provides to tailor care to the needs of the individual patient can be
      realized.

PMID- 17042814
TI  - Patient stories of living with a pressure ulcer.
AB  - AIM: This paper reports the findings of a pilot study exploring the experience of
      older people living with pressure ulcers. BACKGROUND: Pressure ulcers are known
      to be a significant health burden, but little is known of the impact on the
      quality of life of the sufferer. They mainly affect older people, and this is a
      neglected group in previous studies of this topic. METHODS: A Heideggerian
      phenomenological approach was used and patients were recruited if they were over
      65 years of age and had a grade 3 or 4 pressure ulcer that had been present for
      more than a month. Patients were recruited from multiple centres but the data
      were analysed centrally. The study took place in 2003-2004. FINDINGS: Analysis of
      the transcripts revealed three main themes, all with associated subthemes:
      pressure ulcers produce endless pain; pressure ulcers produce a restricted life;
      coping with a pressure ulcer. The endless pain theme had four subthemes: constant
      presence, keeping still, equipment pain and treatment pain. Some patients found
      that keeping still reduced their pain. Several patients also reported that pain
      was exacerbated by their pressure relieving equipment and at dressing change.
      There were three subthemes for the restricted life theme: impact on self, impact
      on others and consequences. Patients found that the pressure ulcer restricted
      their activities and had an impact on their families. In addition, for some, the
      restrictions delayed their rehabilitation. To cope with their pressure ulcers,
      patients developed ways of accepting their situation or comparing themselves with
      others. CONCLUSIONS: Although a pilot, this study has produced a wealth of data
      that demonstrates the impact of pressure ulcers on people. While a larger study
      is required to obtain a European perspective, it is still reasonable to conclude
      that the issues of pain and restrictions should be considered in the development
      of pressure ulcer treatment and prevention guidelines.

PMID- 17042815
TI  - Service users' experiences of 'as needed' psychotropic medications in acute
      mental healthcare settings.
AB  - AIMS: This paper reports a study which aimed to explore service users' views and
      experiences of the processes associated with the prescription and administration
      of 'as needed' (p.r.n.) psychotropic medications in acute mental health settings.
      BACKGROUND: Few studies have explored the use of 'as needed' medication in acute
      mental healthcare settings. Such medication is frequently requested by service
      users, but the literature is unclear about the reasons for these requests or
      service users' experiences of this treatment. METHOD: A convenience sample of 22
      inpatients participated in face-to-face semi-structured interviews exploring
      their treatment experiences of 'as needed' psychotropic medication in acute
      mental health settings in a large city in the United Kingdom in 2005. Thematic
      content analysis was carried out. RESULTS: Interviewees highlighted the value of
      'as needed' medications. However, the process associated with their use was
      perceived as confusing and stigmatizing. Service users had limited understanding
      of and felt unsupported in attempts to use alternatives approaches. Additionally,
      the decision-making and information-giving processes were unclear to them, which
      raises issues of power and control in acute mental health settings. CONCLUSIONS:
      Nurses should take account of the issues of power and control when administering
      'as needed' medication. The provision of adequate treatment information should be
      a priority to enable informed choices to be made about this form of medication.

PMID- 17042816
TI  - Hope promoting strategies of Registered Nurses.
AB  - AIM: This paper describes self-reported hope-promoting strategies used by
      Registered Nurses whilst providing care for older patients in acute and long-term
      care settings. BACKGROUND: The literature is replete with claims that Registered
      Nurses engage in hope facilitation with their patients. However, these claims are
      largely conjecture, with few studies empirically identifying the extent to which
      Registered Nurses use hope interventions with their patients. Further, some
      authors have questioned whether nurses have the necessary skills to undertake
      this vital aspect of care. METHODS: In this Gadamerian hermeneutic
      phenomenological study, undertaken in 2003 in Australia, we used in-depth
      audiotaped interviews to collect data with 14 Registered Nurses. The interviews
      were transcribed verbatim and analysed using the Turner method. FINDINGS: Whilst
      participants clearly reported that they engaged in hope facilitation with older
      patients, there were differences between the reported strategies used by
      Registered Nurses in acute and long-term care settings. Further, the strategies
      reported were not unique to hope promotion and have been variously described in
      the literature on caring, presencing, holistic nursing and therapeutic nursing.
      CONCLUSION: It is clear that participants considered hope promotion to be a vital
      aspect of their care. However, the strategies that they reported were limited and
      not inclusive of many and varied suggestions emerging from published studies on
      hope promotion. Therefore, we recommend that nursing curricula, professional
      development and in-service education programmes place hope facilitation on their
      agenda and foster a culture in which promoting hope is seen as a vital aspect of
      nursing care.

PMID- 17042817
TI  - Heterosexual assumptions in verbal and non-verbal communication in nursing.
AB  - AIM: This paper reports a study of what lesbian women and gay men had to say, as
      patients and as partners, about their experiences of nursing in hospital care,
      and what they regarded as important to communicate about homosexuality and
      nursing. BACKGROUND: The social life of heterosexual cultures is based on the
      assumption that all people are heterosexual, thereby making homosexuality
      socially invisible. Nurses may assume that all patients and significant others
      are heterosexual, and these heteronormative assumptions may lead to poor
      communication that affects nursing quality by leading nurses to ask the wrong
      questions and make incorrect judgements. METHOD: A qualitative interview study
      was carried out in the spring of 2004. Seventeen women and 10 men ranging in age
      from 23 to 65 years from different parts of Sweden participated. They described
      46 experiences as patients and 31 as partners. FINDINGS: Heteronormativity was
      communicated in waiting rooms, in patient documents and when registering for
      admission, and nursing staff sometimes showed perplexity when an informant
      deviated from this heteronormative assumption. Informants had often met nursing
      staff who showed fear of behaving incorrectly, which could lead to a sense of
      insecurity, thereby impeding further communication. As partners of gay patients,
      informants felt that they had to deal with heterosexual assumptions more than
      they did when they were patients, and the consequences were feelings of not being
      accepted as a 'true' relative, of exclusion and neglect. Almost all participants
      offered recommendations about how nursing staff could facilitate communication.
      CONCLUSION: Heterosexual norms communicated unconsciously by nursing staff
      contribute to ambivalent attitudes and feelings of insecurity that prevent
      communication and easily lead to misconceptions. Educational and management
      interventions, as well as increased communication, could make gay people more
      visible and thereby encourage openness and awareness by hospital staff of the
      norms that they communicate through their language and behaviour.

PMID- 17042818
TI  - Stressors and coping of in-hospital haemodialysis patients aged 65 years and
      over.
AB  - AIMS: This paper reports a study to identify the types of stressors experienced
      by in-hospital haemodialysis patients aged 65 years and older, and the use and
      perceived helpfulness of coping strategies to manage these stressors. BACKGROUND:
      Chronic renal failure and its treatments impose a variety of physical and
      psychosocial stressors, which challenge patients. Although the stressors and
      coping strategies of patients having dialysis treatment have been investigated,
      no study has specifically focused on older adults. Such investigation is
      important as the incidence of chronic kidney disease is increasing in this age
      group. METHOD: In this descriptive, correlational study, the Haemodialysis
      Stressor Scale and Jalowiec Coping Scale were used to investigate stressors and
      coping strategies reported by 50 in-hospital haemodialysis patients aged 65 years
      and older. The data were collected in Canada in 2004. RESULTS: Similar to
      previous research, the stressors of fatigue and fluid restrictions ranked highly
      as stressors in this sample. However, interference with social and recreational
      activities were stressors unique to this group. Findings challenge some common
      beliefs about haemodialysis patients. It is commonly believed that these patients
      'get used to' haemodialysis, and therefore the number and troublesomeness of
      stressors decrease over time. This belief was not supported because length of
      time on haemodialysis did not affect participants' appraisal of stressors.
      Another major finding was that older participants in this sample reported the use
      of fewer coping strategies and found them less helpful. CONCLUSION: Further
      research is needed to investigate factors affecting the stressors and coping
      responses of older haemodialysis patients and to determine their impact on health
      outcomes. Such knowledge will assist nurses in developing age-appropriate
      strategies for promoting optimum wellness for these patients who will likely
      spend the remainder of their life adhering to the regimen of haemodialysis.

PMID- 17042819
TI  - Health and quality of life of ventilator-dependent children.
AB  - AIM: This paper reports a qualitative study with ventilator-dependent children
      and their parents, describing their experiences and meanings concerning the
      children's health and quality of life. BACKGROUND: Recent medical advances have
      enabled children to survive premature birth, congenital anomalies, critical
      illness and accidents with long-term use of mechanical ventilation to support
      breathing. In economically developed countries, the number of ventilator
      dependent children is increasing and many require nurse-led home healthcare
      services. Debate has been polarized as to whether life on a ventilator is in the
      best interests of all children. The perspectives of ventilator-dependent children
      are largely absent in the literature. METHODS: Principles derived from
      Heideggerian phenomenology were used to describe how children and their parents
      interpreted and rationalized the quality of the child's 'ventilator-dependent'
      life and their health. The study had two phases with data collection commencing
      in 1998 and completed in 2004. RESULTS: The participants were 35 ventilator
      dependent children, and 50 mothers and 17 fathers of 53 children. Emergent themes
      revealed some common features across this heterogeneous group. Ventilation made
      the children feel better and if they had sufficient breath, they experienced
      better quality of life. It was not possible to delineate the magnitude of health
      gain or benefit, especially amongst preverbal children and those with profound
      sensory impairments. Quality of life equated to quality of life experiences, but
      some children experienced negative social impacts and low self-esteem. Home
      healthcare services were not designed to bring about the desired social outcomes
      that children identified. Parent's accounts showed subtle more negative
      differences. CONCLUSION: The acceptance of children's dependence on machines to
      live has brought about the need for nursing, medical, social and biological
      boundaries to be redefined, especially around children's meanings of their
      health, what they understand to be good quality of life, and what they need to
      achieve it. Flexible, high quality child-focused homecare is likely to improve
      children's outcomes.

PMID- 17042820
TI  - Nursing is different than medicine: ethical difficulties in the process of care
      in surgical units.
AB  - AIM: This paper describes a study of the kinds of ethical difficulties nurses
      face in the process of care in surgical units. BACKGROUND: Nurses face ethically
      difficult situations in trying to find the most appropriate actions to take for
      patients. Differences of opinion with doctors about the treatment and care of
      patients and conflicts between nurses' value systems and those in the
      organization where they are employed are described as sources of ethical
      difficulty. Nurses experience moral distress when institutional constraints
      restrict them from carrying out appropriate moral actions. METHODS: Ten female
      nurses working in surgical units at one university hospital in Norway were
      interviewed as part of a comprehensive investigation into the narratives of
      nurses and doctors about being in ethically difficult situations. The transcribed
      interview texts were subjected to a phenomenological-hermeneutic interpretation.
      The study was conducted during 2004. FINDINGS: The main ethically difficult care
      situations described by the nurses concerned being open and honest, trusting
      patients' complaints, and creating limits to their involvement. Differences in
      opinion with doctors about the treatments, the absence of doctors in the unit and
      limited interest in holistic treatment and care resulted in nurses not receiving
      the medical orders they needed. A heavy workload, lack of time and staffing
      problems resulted in difficult ethical prioritizations and reduced standards of
      care. Shared rooms and beds in the corridors made it difficult to preserve
      patients' rights to privacy and confidentiality. CONCLUSION: Interventions and
      investments are needed to improve the work environment of nurses, especially
      modifying the job constraints of the work environment. The moral responsibility
      for upholding the quality of care in surgical services and hospital performance
      should be more equally distributed between nurses, doctors and hospital managers.
      Discussions and collaboration between and within healthcare disciplines and
      managers should be initiated to establish shared moral understanding of the
      standards of care in hospitals.

PMID- 17042821
TI  - What makes a good midwife? An integrative review of methodologically-diverse
      research.
AB  - AIM: This paper reports an integrative review aimed at answering the question:
      'What makes a good midwife?' BACKGROUND: A research-based definition of a good
      midwife which can be used as an operational definition in research and as a basis
      for curriculum development could not be found. Research in nursing has identified
      that patients and nurses may give different responses when asked about the most
      important aspects of nurses' contribution to care. It is also possible that views
      of how to define a good midwife might differ. METHODS: A four-stage systematic
      review process was used, consisting of protocol development, carrying out the
      search, appraisal/analysis of the papers retrieved, and synthesis of the
      information. The initial search covered the period from 1993 and used the
      keywords 'midwi*', 'nurse-midwi*' and 'good'. This was later extended to include
      the terms 'exemplary', 'excellent' and 'superb' as synonyms of 'good', and 'bad'
      as its antonym. The integrative review was descriptive and focussed on extracting
      from the papers the findings that contributed to answering the research question.
      FINDINGS: Thirty-three research-based papers were included in the review, and
      these had used a range of approaches and methods. Eight key concepts were derived
      from the data: attributes of a midwife, education, research, what a midwife does,
      care organization, other professionals, partners and an international
      perspective. CONCLUSION: Having good communication skills made the greatest
      contribution to being 'a good midwife', while being compassionate, kind,
      supportive (affective domain), knowledgeable (cognitive domain) and skilful
      (psychomotor domain) also made major contributions. Being involved in education
      and research were necessary requirements, and midwives' abilities to treat women
      as individuals, adopt a caring approach, and 'be there' for women were essential.
      A good midwife can compensate for poor management systems, but women should be
      able to choose who provides their care, and partners should be involved in this
      care.

PMID- 17042822
TI  - The art of public health nursing: using confession techne in the sexual health
      domain.
AB  - AIM: This paper explores the sexual health interview from a critical perspective,
      and to demonstrate how the confession ritual involved in this interview is
      implicated in the construction of subjectivities (meaning identities) as well as
      in fostering self-surveillance (self-regulation). BACKGROUND: The concept of
      public health depends primarily on several surveillance tools that monitor both
      the incidence and prevalence rates of certain diseases. Within the subgroup of
      infectious diseases, sexually transmitted infections comprise a group that is
      closely monitored. As a result, surveillance techniques, including policing
      sexual practices, are part of the public health worker's mandate. METHOD: Using a
      Foucauldian perspective, we demonstrate that confession is a political technology
      in the sexual health domain. FINDINGS: As one group of frontline workers in the
      field of sexual health, nurses are responsible for data collection through
      methods such as interviewing clients. Nurses play an integral role in the sexual
      health experience of clients as well as in the construction of the client's
      subjectivity. We strongly believe that a Foucauldian perspective could be useful
      in explaining certain current client behavioural trends (for example, an
      avoidance by at-risk groups of interactions with nurses in sexual health clinics)
      being observed in sexual health clinics across the Western hemisphere.
      CONCLUSION: Clinicians need to be aware of the confessional nature of their
      questions and provide requested services rather than impose services that they
      determine to be important and relevant. By appreciating that the sexual health
      interview is an invasive and embarrassing sexual confession, healthcare providers
      and policy-makers may be better able to design and implement more user-oriented,
      population-sensitive sexual health services.

PMID- 17042823
TI  - Work-related fatigue and recovery: the contribution of age, domestic
      responsibilities and shiftwork.
AB  - AIM: This paper reports a study of the relationship between age, domestic
      responsibilities (being partnered and having dependents), recovery from shiftwork
      related fatigue and the evolution of maladaptive health outcomes among full-time
      working female nurses. BACKGROUND: Several studies have suggested that full-time
      working women with family responsibilities are at greater risk of developing work
      related fatigue problems than single women without these responsibilities.
      METHOD: A questionnaire was distributed in 2004 to 2400 nurses at two hospitals
      in Australia, and 1280 responses were obtained (response rate 54%). The data from
      a purposive sample of 846 full-time working nurses are reported here. FINDINGS:
      Domestic responsibilities were not related to differences in fatigue and
      recovery. Our results suggested that for full-time shiftworking nurses, being
      part of a family structure, may actually be protective against the development of
      maladaptive fatigue. The most important factor determining maladaptive fatigue
      outcome was shift pattern worked, particularly rotation including night duty. The
      effect of age was equivocal. The youngest age group reported the highest fatigue
      and poorest recovery compared to the oldest group, who reported the best
      characteristics. However, this latter group may represent a particularly well
      adapted 'survivor cohort'. The relationship between age and fatigue was partly
      confounded by older, experienced, nurses with greater job responsibilities,
      working fewer multiple shifts including night duty. In general, increasing age
      was not associated with poorer recovery or higher maladaptive fatigue.
      CONCLUSIONS: Unpredictable internal shift rotations, including night duty, which
      are traditional and typical in nursing, are inimical to maintaining nurses'
      health. More creative approaches to rostering for nurses working multiple shifts
      are a necessary step towards reducing wastage from the profession due to chronic
      work-related fatigue. Younger nurses in particular, may need more support than is
      currently recognized if they are to be retained within the profession.

PMID- 17042826
TI  - Rational approaches to the neurobiologic study of youth at risk for bipolar
      disorder and suicide.
AB  - OBJECTIVES: The aims of this paper are to provide an overview of neuroimaging
      findings specific to bipolar disorder and suicide, and to consider rational
      approaches to the design of future in vivo studies in youth at risk. METHODS:
      Neuroimaging and related neurobiological literature pertaining to bipolar
      disorder and suicide in adult and pediatric samples was reviewed in a non
      quantitative manner. RESULTS: Specific structural and functional brain findings
      in bipolar disorder are described, where possible in the context of relevant
      current neurobiological theories of etiology. Diagnostic and prognostic
      implications are discussed. CONCLUSIONS: The simultaneous use of complementary
      neurobiological approaches may be a powerful way of identifying and validating
      factors reliably associated with bipolar disorder and suicide. A profile of
      neurobiological markers with which to screen for bipolar disorder and suicide
      risk may provide for earlier and more accurate diagnosis, perhaps even in the pre
      or subsyndromal stages in high-risk youth.

PMID- 17042828
TI  - Correlates of suicide attempt history in bipolar disorder: a stress-diathesis
      perspective.
AB  - OBJECTIVES: Distinguishing clinical characteristics of bipolar patients who have
      made a suicide attempt may help to identify at-risk individuals. We sought to
      identify such factors and to consider them within a stress-diathesis model of
      suicidal behavior. METHODS: Patients with bipolar disorder (N = 96) were compared
      with respect to the presence or absence at baseline evaluation of a history of
      suicide attempt. We used multiple logistic regression analysis to assess the
      unique associations of independent variables to history of a past suicide
      attempt. RESULTS: The regression analysis showed that a history of suicide
      attempt in bipolar disorder was associated with greater recent suicidal ideation,
      more psychiatric hospitalizations, lifetime aggressive traits and an earlier age
      at onset of a first mood episode. CONCLUSIONS: Aggressive traits and early
      treatment of mood disorders, especially major depressive episodes, are potential
      targets for suicide prevention in bipolar disorder.

PMID- 17042827
TI  - A prospective study of the association of cerebrospinal fluid monoamine
      metabolite levels with lethality of suicide attempts in patients with bipolar
      disorder.
AB  - OBJECTIVES: Bipolar disorder is a severe illness that is associated with suicidal
      behavior. A biological predictor of highly lethal suicide attempts in patients
      with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid
      (CSF) monoamine metabolite levels are related to lethality of suicide attempts in
      bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid
      (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)
      levels and maximum lethality of suicide attempts at baseline and during a 2-year
      follow up. METHODS: Twenty-seven bipolar depressed patients participated in the
      study. Demographic and clinical parameters were examined and recorded. Lumbar
      punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high
      performance liquid chromatography with electrochemical detection. Following
      discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each
      follow-up interview included an in-depth assessment of suicidal behavior during
      the intervening time period. RESULTS: Six subjects made suicide attempts during
      the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up
      period had higher aggression and hostility scale scores compared to bipolar
      subjects who did not make a suicide attempt during the follow-up period. CSF 5
      HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality
      of suicide attempts during the 2-year follow-up period. CONCLUSIONS: Our finding
      is the first observation that CSF monoamine metabolite levels may be predictors
      of lethality of suicide attempts in patients with bipolar disorder. Further
      studies are necessary to answer the question whether CSF monoamine metabolite
      levels are clinically useful biochemical predictors of highly lethal suicide
      attempts or completed suicides.

PMID- 17042829
TI  - A comparison of the medical lethality of suicide attempts in bipolar and major
      depressive disorders.
AB  - OBJECTIVES: Among mood disorders, bipolar disorder (BPD) is often noted to
      involve the highest rates of suicide attempts and possibly of completion. This
      study sought to determine whether suicide attempters with BPD exhibit suicide
      attempts with higher lethality than attempters with major depressive disorder
      (MDD) and to explore differences in clinical features associated with suicidal
      acts. METHODS: Mood disordered suicide attempters were interviewed about Axis I
      and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal
      ideation, the medical lethality of their most severe suicide attempt, severity of
      depression, hopelessness, lifetime aggression, and impulsivity. RESULTS: The
      maximum lethality of suicidal acts tended to be higher among BPD attempters
      compared with those with MDD. However, there were no differences in the number of
      suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD
      reported higher levels of aggression and impulsivity but less hopelessness
      compared with MDD attempters. These differences could not be explained by Cluster
      B personality disorder comorbidity. Of note, within the BPD group, but not the
      MDD group, males reported suicidal acts with higher lethality. Multivariate
      analyses suggested that risk for more lethal suicide attempts is associated with
      BPD and male sex and that bipolar males appear to be especially vulnerable to
      these behaviors. CONCLUSIONS: Males with BPD make more lethal suicide attempts
      than females with BPD, an effect not observed among the MDD sample. Our findings
      suggest that higher rates of suicidal behavior in BPD may be due to a specific
      effect of BPD on males, leading to more dangerous suicidal behaviors. This
      effect, together with the larger proportion of males in the BPD group compared
      with the MDD group may lead to higher rates of reported attempted and completed
      suicide.

PMID- 17042830
TI  - Prospective predictors of suicide and suicide attempts in 1,556 patients with
      bipolar disorders followed for up to 2 years.
AB  - OBJECTIVES: Bipolar disorders are associated with high rates of suicide attempts
      (SAs) and completions. Several factors have been reported to be associated with
      suicide in persons with bipolar disorder, but most studies to date have been
      retrospective and have not utilized multivariate statistics to account for the
      redundant prediction among variables submitted for analysis. METHODS: This study
      examined the association between baseline clinical and demographic variables and
      subsequent SAs and completions through 2 years of follow-up of participants in
      the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern
      mixture model. RESULTS: Of the sample with complete data (n = 1,556), 57 patients
      (3.66%) experienced an SA or completion (CS). Several variables predicted
      suicidality (SA + CS) in this data set when considered alone, but after
      controlling for redundant prediction from other baseline characteristics, only
      history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days
      depressed in the past year (OR = 1.16, p = 0.036) were significantly associated
      with SAs and completions. A secondary analysis included a greater number of
      variables but a smaller sample size (n = 1,014). In the secondary analyses, only
      prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). CONCLUSIONS:
      These results indicate that patients with bipolar disorder who present with a
      history of SAs are over four times as likely to have a subsequent SA or
      completion. Further studies are needed to evaluate and prevent future attempts in
      this high-risk cohort.

PMID- 17042831
TI  - Prospective study of risk factors for attempted suicide among patients with
      bipolar disorder.
AB  - OBJECTIVE: There are few prospective studies on risk factors for attempted
      suicide among representative samples of psychiatric patients with bipolar I and
      II disorders. We conducted a prospective study to investigate risk for suicide
      attempts among a secondary-level sample of psychiatric in- and outpatients with
      bipolar disorder (BD). METHODS: In the Jorvi Bipolar Study (JoBS), 1,630
      psychiatric in- and outpatients from three Finnish cities were screened for BDs
      with the Mood Disorder Questionnaire (MDQ). Using the Structured Clinical
      Interview for DSM-IV Disorders (SCID)-I and -II, 191 patients were diagnosed with
      BDs (90 bipolar I and 101 bipolar II). Information on suicide attempts during the
      follow-up was obtained for 176 patients (92%) at the 6-month follow-up and for
      160 patients (84%) at the 18-month follow-up. RESULTS: During the 18-month follow
      up 20% of patients (35/176) attempted suicide. In a Cox regression model,
      baseline previous suicide attempts (OR 3.8, 95% CI 1.7-8.8; p = 0.001),
      hopelessness (OR 1.2, 95% CI 1.1-1.3; p < 0.001), depressive phase at index
      episode (OR 2.4, 95% CI 1.1-5.3; p = 0.03) and younger age at intake (OR 0.94,
      95% CI 0.91-0.97; p < 0.001) were independent risk factors for suicide attempts
      during follow-up, whereas factors such as bipolar I or II, or comorbidity did not
      reach statistical significance. CONCLUSIONS: During a medium-term follow-up, as
      many as one-fifth of random psychiatric patients with BD attempted suicide, which
      highlights the public health importance of suicidal behavior in BD. Previous
      suicide attempts, hopelessness and depressive phase were the key indicators of
      risk.

PMID- 17042832
TI  - Clinical predictors of suicidal acts after major depression in bipolar disorder:
      a prospective study.
AB  - OBJECTIVE: This study determined the clinical predictors of suicidal behavior
      during a 2-year follow-up of patients with bipolar disorder presenting with a
      major depressive episode (MDE). METHOD: Sixty four patients with DSM-III-R
      bipolar disorder were assessed at presentation for treatment of an MDE.
      Correlates of past suicidal behavior were determined by comparing patients with
      and without a history of suicide attempts using a t-test, Wilcoxon test or chi
      squared test of independence on individual explanatory variables. Putative
      predictors of attempts during the follow-up period were tested separately using
      Cox proportional hazards regression analysis. RESULTS: Twelve of 64 patients had
      at least one suicide attempt in the follow-up period, five of them attempted in
      the first 2 months and seven around or shortly after the 1-year follow-up visit.
      All attempters had a history of past suicide attempts. Most predictors of future
      suicidal behavior were correlates of past suicidal behavior. Family history of
      suicide acts and comorbid borderline personality disorder predicted early
      attempts, while younger age, high hostility scores, number of past attempts,
      subjective pessimism as reflected in depression and suicidal ideation, and few
      reported reasons for living predicted suicidal acts during the whole period.
      CONCLUSION: In this data set of bipolar patients we noted an intriguing picture
      of two clusters of suicide attempts. Hostility was the strongest risk factor.
      These findings may have implications in both the identification of at-risk
      patients and the timing of clinical interventions including aggressive
      pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive
      symptomatology.

PMID- 17042833
TI  - Antidepressants and suicidal behavior in bipolar disorder.
AB  - Patients with bipolar disorder are at very high risk for suicidal ideation, non
      fatal suicidal behaviors and suicide and are frequently treated with
      antidepressants. However, no prospective, randomized, controlled study
      specifically evaluating an antidepressant on suicidality in bipolar disorder has
      yet been completed. Indeed, antidepressants have not yet been shown to reduce
      suicide attempts or suicide in depressive disorders and may increase suicidal
      behavior in pediatric, and possibly adult, major depressive disorder. Available
      data on the effects of antidepressants on suicidality in bipolar disorder are
      mixed. Considerable research indicates that mixed states are associated with
      suicidality and that antidepressants, especially when administered as
      monotherapy, are associated with both suicidality and manic conversion. In
      contrast, growing research suggests that antidepressants administered in
      combination with mood stabilizers may reduce depressive symptoms in patients with
      bipolar depression. Further, the only prospective, long-term study evaluating
      antidepressant treatment and mortality in bipolar disorder, although open-label,
      found antidepressants and/or antipsychotics in combination with lithium, but not
      lithium alone, reduced suicide in bipolar and unipolar patients (Angst F, et al.
      J Affect Disord 2002: 68: 167-181). We conclude that antidepressants may induce
      suicidality in a subset of persons with depressive (and probably anxious)
      presentations; that this induction may represent a form of manic conversion, and
      hence a bipolar phenotype, and that lithium's therapeutic properties may include
      the ability to prevent antidepressant-induced suicidality.

PMID- 17042834
TI  - Suicidal risk in bipolar I disorder patients and adherence to long-term lithium
      treatment.
AB  - OBJECTIVES: Among the well-established treatments for bipolar disorder (BPD),
      lithium continues to offer an unusually broad spectrum of benefits that may
      include reduction of suicidal risk. METHODS: We examined the association of
      suicidal acts with adherence to long-term lithium maintenance treatment and other
      potential risk factors in 72 BP I patients followed prospectively for up to 10
      years at a Mood Disorders Research Center in Spain. RESULTS: The observed rates
      of suicide were 0.143, and of attempts, 2.01%/year, with a 5.2-fold (95% CI: 1.5
      18.6) greater risk among patients consistently rated poorly versus highly
      adherent to lithium prophylaxis (11.4/2.2 acts/100 person-years). Treatment non
      adherence was associated with substance abuse, being unmarried, being male, and
      having more hypomanic-manic illness and hospitalizations. Suicidal risk was
      higher with prior attempts, more depression and hospitalization, familial mood
      disorders, and being single and younger, as well as treatment non-adherence, but
      with neither sex nor substance abuse. In multivariate analysis, suicidal risk was
      associated with previous suicidality > poor treatment adherence > more depressive
      episodes > younger age. CONCLUSIONS: The findings support growing evidence of
      lower risk of suicidal acts during closely monitored and highly adherent, long
      term treatment with lithium and indicate that treatment adherence is a
      potentially modifiable factor contributing to antisuicidal benefits.

PMID- 17042835
TI  - Decreased risk of suicides and attempts during long-term lithium treatment: a
      meta-analytic review.
AB  - OBJECTIVES: To update and extend comparisons of rates of suicides and suicide
      attempts among patients with major affective disorders with versus without long
      term lithium treatment. METHODS: Broad searching yielded 45 studies providing
      rates of suicidal acts during lithium treatment, including 34 also providing
      rates without lithium treatment. We scored study quality, tested between-study
      variance, and examined suicidal rates on versus off lithium by meta-analytic
      methods to determine risk ratios (RRs) and 95% confidence intervals (CI).
      RESULTS: In 31 studies suitable for meta-analysis, involving a total of 85,229
      person-years of risk-exposure, the overall risk of suicides and attempts was five
      times less among lithium-treated subjects than among those not treated with
      lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found
      with other meta-analytic methods, as well as for completed versus attempted
      suicide, and for bipolar versus major mood disorder patients. Studies with higher
      quality ratings, including randomized, controlled trials, involved shorter
      exposures with somewhat lesser lithium superiority. Omitting one very large study
      or those involving lithium-discontinuation had little effect on the results. The
      incidence-ratio of attempts-to-suicides increased 2.5 times with lithium
      treatment, indicating reduced lethality of suicidal acts. There was no indication
      of bias toward reporting positive findings, nor were outcomes significantly
      influenced by publication-year or study size. CONCLUSIONS: Risks of completed and
      attempted suicide were consistently lower, by approximately 80%, during treatment
      of bipolar and other major affective disorder patients with lithium for an
      average of 18 months. These benefits were sustained in randomized as well as open
      clinical trials.

PMID- 17042836
TI  - Family-focused treatment of the suicidal bipolar patient.
AB  - OBJECTIVES: Bipolar patients are at high risk for suicidal ideation and attempts.
      Suicidal behavior is correlated with poor family communication and/or high levels
      of intrafamilial conflict, particularly among adolescent bipolar patients. This
      article describes the application of family-focused therapy (FFT) as an adjunct
      to pharmacotherapy in the management of suicidal ideation and behavior among
      bipolar patients. METHODS: We describe the empirical basis of FFT in studies of
      adult and adolescent patients. We then describe the manner by which the three
      modules of FFT - psychoeducation, communication skills training and problem
      solving - are adapted to address the clinical issues presented by suicidal
      bipolar adults or adolescents and their families. RESULTS: Key objectives of the
      treatment are to help the family recognize that suicidal behavior is a part of
      the pathophysiology of bipolar disorder but that it is also to some extent under
      environmental control. Thus, the family is in a unique position to develop and
      help assure the success of a suicide prevention contract. A case study of an
      adolescent with suicidal behavior is presented. CONCLUSIONS: Future research
      should include a focus on: (i) cross-cultural issues in suicide and bipolar
      disorder; and (ii) the adaptation of interventions shown to be effective in
      reducing suicidal behaviors in non-bipolar populations.

PMID- 17042837
TI  - What is vital to measure?

PMID- 17042838
TI  - The cat in the kitchen: problems with the Pippa technique.

PMID- 17042839
TI  - A randomised controlled trial of the effect of continuous electronic
      physiological monitoring on the adverse event rate in high risk medical and
      surgical patients.
AB  - We conducted a randomised controlled trial of mandated five-channel physiological
      monitoring vs standard care, in acute medical and surgical wards in a single UK
      teaching hospital. In all, 402 high-risk medical and surgical patients were
      studied. The primary outcome was the proportion of patients experiencing one or
      more major adverse events, including urgent staff calls, changes to higher care
      levels, cardiac arrests or death, in 96 h following randomisation. Secondary
      outcomes were the proportion of patients requiring acute treatment changes, and
      the 30-day and hospital mortality. In the 96 h following randomisation, 113 (56%)
      patients in the monitored arm and 116 (58%) in the control arm (OR 0.94, 95% CI
      0.63-1.40, p = 0.76) had a major event. An acute change in treatment was
      necessary in 107 (53%) monitored patients and 101 (50%) control patients (OR
      0.55, 95% CI 0.87-1.29). Thirty-four (17%) monitored patients and 35 (17%)
      control patients died within 30 days. Thirteen patients in the control group
      received full five-channel monitoring at the request of the ward staff. We
      conclude that mandated electronic vital signs monitoring in high risk medical and
      surgical patients has no effect on adverse events or mortality.

PMID- 17042840
TI  - Effect of propofol on seizure-like phenomena and electroencephalographic activity
      in children with epilepsy vs children with learning difficulties.
AB  - There is an ongoing debate as to whether propofol exhibits pro- or anticonvulsant
      effects, and whether it should be used in patients with epilepsy. We
      prospectively assessed the occurrence of seizure-like phenomena and the effects
      of intravenous propofol on the electroencephalogram (EEG) in 25 children with
      epilepsy (mean (SD) age: 101 (49) months) and 25 children with learning
      difficulties (mean (SD) age: 52 (40) months) undergoing elective sedation for MRI
      studies of the brain. No child demonstrated seizure-like phenomena of epileptic
      origin during and after propofol sedation. Immediately after stopping propofol,
      characteristic EEG changes in the epilepsy group consisted of increased beta wave
      activity (23/25 children), and suppression of pre-existing theta rhythms (11/16
      children). In addition, 16 of 18 children with epilepsy and documented EEG
      seizure activity demonstrated suppression of spike-wave patterns after propofol
      sedation. In all 25 children with learning difficulties an increase in beta wave
      activity was seen. Suppression of theta rhythms occurred in 11 of 12 children at
      the end of the MRI study. In no child of either group was a primary occurrence or
      an increase in spike-wave patterns seen following propofol administration. The
      occurrence of beta wave activity (children with learning difficulties and
      epilepsy group) and suppression of spike-wave patterns (epilepsy group) were
      transient, and disappeared after 4 h. This study demonstrates characteristic,
      time-dependent EEG patterns induced by propofol in children with epilepsy and
      learning difficulties. Our data support the concept of propofol being a sedative
      hypnotic agent with anticonvulsant properties as shown by depression of spike
      wave patterns in children with epilepsy and by the absence of seizure-like
      phenomena of epileptic origin.

PMID- 17042841
TI  - A comparison of an anterior jaw lift manoeuvre with the Berman airway for
      assisting fibreoptic orotracheal intubation.
AB  - This study compared the efficacy of an anterior jaw lift manoeuvre with that of
      the Berman airway in clearing the upper airway during oral fibreoptic tracheal
      intubation in anaesthetised, paralysed patients. Fifty patients were randomly
      assigned to undergo fibreoptic-assisted intubation with one method, followed by
      crossover to the alternative method. The time taken to view the vocal cords was
      the primary endpoint, and we also noted the rate of failure to view the cords,
      i.e. cords not seen after 120 s of endoscopy. Anterior jaw lift yielded
      significantly shorter times to view the vocal cords (median [interquartile range;
      range]: 22 [17-46; 7-120] s vs 40 [29-67; 21-120] s, p = 0.001) and a higher
      success rate (49/50 vs 42/50, p = 0.014). We conclude that the anterior jaw lift
      is more effective than the Berman device for achieving airway clearance in this
      setting.

PMID- 17042842
TI  - A comparison of cyclizine and granisetron alone and in combination for the
      prevention of postoperative nausea and vomiting.
AB  - We conducted a randomised double-blinded study of 960 women undergoing day-case
      surgery to determine whether combination anti-emetic therapy of granisetron and
      cyclizine was more effective at decreasing the incidence of postoperative nausea
      and vomiting than these agents used alone. The women were randomly allocated to
      three groups to receive intravenous granisetron 1 mg, cyclizine 50 mg or both
      before induction of general anaesthesia. The incidence of postoperative nausea
      and vomiting was 77/322 (24%) in the granisetron group, 73/316 (23%) in the
      cyclizine group and 53/322 (17%) in those women given both drugs (p = 0.04).
      There was no difference in the requirement for rescue anti-emetic drugs. There
      were no differences in the anaesthetic techniques used in the three groups. We
      conclude that the risk of postoperative nausea and vomiting is less with
      cyclizine and granisetron given together than with either given alone.

PMID- 17042843
TI  - The role of magnesium as an adjuvant during general anaesthesia.
AB  - Magnesium sulphate is used extensively in the treatment of eclampsia, and is also
      used to treat refractory arrhythmias, asthma, myocardial ischaemia and acute
      respiratory failure. We studied the interaction between magnesium sulphate and
      the anaesthetic agents propofol, rocuronium bromide and fentanyl citrate. This
      randomised, double blind study was conducted in 50 patients. The magnesium group
      A (n = 25) received 30 mg x kg(-1) magnesium sulphate before induction of
      anaesthesia and 10 mg x kg(-1) continuously intra-operatively until the end of
      surgery. Group B (n = 25) received the same volume of isotonic saline. Propofol,
      rocuronium and fentanyl infusions were started and the patients lungs' were
      ventilated with 33% oxygen in nitrous oxide. Anaesthetic depth was maintained at
      a bispectral index value of between 40 and 60. Muscle relaxation was maintained
      at a train-of-four count of 1 throughout surgery using neuromuscular monitoring.
      The fentanyl infusion was titrated to haemodynamic variables: heart rate and
      blood pressure. We concluded that magnesium sulphate has anaesthetic, analgesic
      and muscle relaxation effects and significantly reduces the drug requirements of
      propofol, rocuronium and fentanyl during anaesthesia.

PMID- 17042844
TI  - A comparison of nerve stimulator guided paravertebral block and ilio-inguinal
      nerve block for analgesia after inguinal herniorrhaphy in children.
AB  - The aim of this study was to compare the efficacy of nerve stimulator guided
      paravertebral block with ilio-inguinal nerve block in children undergoing
      inguinal herniorrhaphy. Eighty children were randomly allocated to receive either
      paravertebral block or ilio-inguinal nerve block. Each block was evaluated in
      terms of intra-operative haemodynamic stability, postoperative pain scores at
      rest, on movement and during activity, requirement for supplemental analgesia and
      parental satisfaction. Haemodynamic stability was maintained significantly better
      during sac traction in the paravertebral block group (p < 0.005). Pain scores and
      analgesic consumption were significantly lower in the paravertebral block group
      during the postoperative follow-up period (p < 0.05). Parental satisfaction
      (93%vs 69%) and surgeon satisfaction (93%vs 64%) were significantly higher in the
      paravertebral block group (p < 0.05). Paravertebral blockade improved and
      prolonged postoperative analgesia, and was associated with greater parental and
      surgeon satisfaction when compared to ilio-inguinal nerve block.

PMID- 17042845
TI  - Thomas the Tank Engine and Friends improve the understanding of oxygen delivery
      and the pathophysiology of hypoxaemia.
AB  - Understanding basic pathophysiological principles underpins the practice of many
      healthcare workers, particularly in a critical care setting. Undergraduate
      curricula have the potential to separate physiology teaching from clinical
      contexts, making understanding difficult. We therefore assessed the use of
      analogous imagery as an aid to understanding. Two groups of first year
      physiotherapy students were randomly assigned to receive either a control lecture
      (oxygen delivery and hypoxaemia) or a study lecture (control lecture plus images
      of a train set delivering rocks: an analogy to oxygen delivery.) Qualitative
      assessment of the lectures showed a significant (p < 0.001) improvement in
      understanding by the study group, and increased the proportion of students that
      found the lecture 'interesting and stimulating' (p = 0.01). Quantitative
      assessment demonstrated a significant increase in the multiple choice
      questionnaire marks of the study group (p = 0.03). In conclusion, analogous
      imagery can significantly increase the understanding of this physiological
      concept.

PMID- 17042846
TI  - Brain stem death testing after thiopental use:A survey of UK neuro critical care
      practice.
AB  - A postal survey was conducted to determine how thiopental is used in UK
      neurosurgery critical care units. Thirty units were contacted and 26 replied.
      Thiopental is used in 23 units. The majority (60%) of these units govern the use
      of thiopental with protocols or guidelines and 74% use cerebral monitoring to
      guide dosage. When patients have had thiopental, 20 units delay brain stem
      testing, two will not perform tests and one unit incorporates cerebral
      angiography into their protocol. Twelve units use serum thiopental assays in
      their brain stem testing procedures, but there is wide variation in the
      interpretation of the results. We found inconsistency and confusion surrounding
      brain stem testing in this patient group, raising the possibility of misdiagnosis
      of brain stem death.

PMID- 17042847
TI  - An evaluation of protocolised weaning on the duration of mechanical ventilation.
AB  - Using a before and after study design, we compared protocolised weaning from
      mechanical ventilation with usual non-protocolised practice in intensive care.
      Outcomes (duration of mechanical ventilation, duration of intubation, intensive
      care stay) and complications (re-intubations, tracheostomy, mortality) were
      compared between baseline (Phase I) and following implementation of protocolised
      weaning (Phase II). Over the same period, we collected data in a second
      (reference) unit to monitor practice changes over time. In the intervention unit,
      outcomes were longer in Phase II compared with Phase I (all p < 0.005). When
      adjusted for admission APACHE II score and diagnostic category, only intensive
      care stay remained significantly longer (p = 0.002). There were significantly
      more tracheostomies in Phase II (p = 0.004). The reference unit demonstrated no
      statistically significant differences in study outcomes or complications between
      Phases. Protocolised weaning did not reduce the duration of mechanical
      ventilation and was not associated with an increased rate of re-intubation or
      intensive care unit mortality.

PMID- 17042848
TI  - An observational study of changes to long-term medication after admission to an
      intensive care unit.
AB  - Many patients admitted to intensive care units consume long-term medication. New
      drugs may be commenced during intensive care intended for the short term or
      longer. Patients are often cared for by several teams during hospital admission
      and long-term medication may inadvertently be permanently discontinued. Following
      admission, new therapies relevant only in the short term could be continued
      beyond intensive care and hospital discharge. We conducted a retrospective
      analysis of drug prescription by examining patients' notes and charts before,
      during and after intensive care admission. Of 197 drugs prescribed up to
      intensive care admission to 59 patients, 112 (57%) were stopped. Ninety-nine of
      these were not reintroduced by intensive care discharge and 34 were not
      reintroduced by hospital discharge. Of 154 drugs commenced during intensive care,
      96 (62%) had no listed reason for their introduction. Twenty-eight were continued
      beyond hospital discharge, some without apparent ongoing indication. Reliable
      mechanisms to prevent prescription errors are required.

PMID- 17042849
TI  - A comparison of tracheal intubation using the Airtraq or the Macintosh
      laryngoscope in routine airway management: A randomised, controlled clinical
      trial.
AB  - The Airtraq laryngoscope is a novel single use tracheal intubation device. We
      compared the Airtraq with the Macintosh laryngoscope in patients deemed at low
      risk for difficult intubation in a randomised, controlled clinical trial. Sixty
      consenting patients presenting for surgery requiring tracheal intubation were
      randomly allocated to undergo intubation using a Macintosh (n = 30) or Airtraq (n
      = 30) laryngoscope. All patients were intubated by one of four anaesthetists
      experienced in the use of both laryngoscopes. No significant differences in
      demographic or airway variables were observed between the groups. All but one
      patient, in the Macintosh group, was successfully intubated on the first attempt.
      There was no difference between groups in the duration of intubation attempts. In
      comparison to the Macintosh laryngoscope, the Airtraq resulted in modest
      improvements in the intubation difficulty score, and in ease of use. Tracheal
      intubation with the Airtraq resulted in less alterations in heart rate. These
      findings demonstrate the utility of the Airtraq laryngoscope for tracheal
      intubation in low risk patients.

PMID- 17042850
TI  - Comparison of forced-air warming and electric heating pad for maintenance of body
      temperature during total knee replacement.
AB  - We conducted a randomised controlled trial to compare the efficacy of forced-air
      warming (Bair Hugger(trade mark), Augustine Medical model 500/OR, Prairie, MN)
      with that of an electric heating pad (Operatherm 202, KanMed, Sweden) for
      maintenance of intra-operative body temperature in 60 patients undergoing total
      knee replacement under combined spinal-epidural anaesthesia. Intra-operative
      tympanic and rectal temperatures and verbal analogue score for thermal comfort
      were recorded. There were no differences in any measurements between the two
      groups, with mean (SD) final rectal temperatures of 36.8 (0.4) degrees C with
      forced-air warming and 36.9 (0.4) degrees C with the electric pad. The heating
      pad is as effective as forced-air warming for maintenance of intra-operative body
      temperature.

PMID- 17042851
TI  - Total spinal anaesthesia after an attempted brachial plexus block using the
      posterior approach.
AB  - A 66-year-old patient scheduled for elective shoulder surgery underwent a
      brachial plexus block using the posterior approach. Shortly after injection of
      the local anaesthetic, he rapidly became unresponsive and apnoeic. We identify
      the possible reasons for this occurrence and discuss the place of the posterior
      approach in brachial plexus anaesthesia.

PMID- 17042852
TI  - Acquired C1 esterase inhibitor deficiency: An atypical first presentation intra
      operatively.
AB  - We report a case of airway difficulties encountered as a result of blistering,
      oedema and bleeding from the oropharyngeal mucosa of an 85-year-old female
      undergoing an elective excision of a submandibular neck lump. This led to a delay
      in extubation by several hours. The patient was subsequently found to have an
      acquired form of C1 esterase inhibitor deficiency considered to be consequent of
      haematological malignancy.

PMID- 17042853
TI  - The management of severe emergence agitation using droperidol.
AB  - Emergence agitation can occur following recovery from general anaesthesia. The
      patient may exhibit aggressive behaviour, disorientation, agitation and
      restlessness. Untreated, this complication may result in significant morbidity.
      We report two cases where droperidol was successfully used in the management of
      severe emergence agitation. In the first case, droperidol was administered to
      prevent the occurrence of postoperative agitation in a patient known to suffer
      from this condition following previous general anaesthetics. In the second case,
      droperidol was used to treat emergence agitation in a morbidly obese patient with
      a difficult airway who was aggressive and difficult to restrain. Both of these
      patients remained calm and co-operative, with stable cardio-respiratory
      parameters, following the administration of droperidol and showed no further
      signs of agitation. We suggest that droperidol is an effective medication that
      may be used to prevent and treat severe emergence agitation due to its rapid
      sedative effect and minimal cardio-respiratory depression.

PMID- 17042854
TI  - Lipid emulsion for local anaesthetic toxicity.

PMID- 17042856
TI  - Local anaesthetic toxicity: prevention or cure?

PMID- 17042858
TI  - The difference between the use (or not) of 'resuscitative measures' and 'Do Not
      Attempt Resuscitation' requests.

PMID- 17042859
TI  - Lipid emulsion for local anaesthetic toxicity.

PMID- 17042860
TI  - Decision making and decision analysis.

PMID- 17042861
TI  - Emergency Caesarean section--best practice.

PMID- 17042864
TI  - The effects of general anaesthesia on children.

PMID- 17042865
TI  - Sub-mental vs. retromolar intubation.

PMID- 17042866
TI  - The Triservice Anaesthetic Apparatus--an alternative configuration.

PMID- 17042867
TI  - Burn following use of the Suntouch warmer.

PMID- 17042868
TI  - Variability of Guedel-type airways.

PMID- 17042870
TI  - Ultrasound-guided ilio-inguinal and rectus sheath nerve blocks.

PMID- 17042871
TI  - Awareness, dreaming or steroid-induced psychosis?

PMID- 17042872
TI  - Nasogastric tube insertion--another technique.

PMID- 17042873
TI  - Povidone-iodine antisepsis before ophthalmic surgery.

PMID- 17042874
TI  - Phantom capnograph.

PMID- 17042878
TI  - Patterns of oscillatory behavior in different human systems: a special reference
      to psychiatry and techniques to quantify such patterns.

PMID- 17042880
TI  - Approximate entropy of self-reported mood prior to episodes in bipolar disorder.
AB  - BACKGROUND: Approximate entropy (ApEn) measures regularity in time series data,
      while traditional linear statistics measure variability. Using self-reported mood
      data from patients with bipolar disorder, this preliminary study addressed
      whether ApEn could distinguish (i) the 60 days prior to the start of a manic or
      depressed episode from the 60 days prior to a month of euthymia, and (ii) the 60
      days prior to a manic episode from the 60 days prior to a depressed episode.
      METHODS: Self-reported mood data from 49 outpatients with bipolar disorder
      receiving standard treatment were analysed. The data contained 27 episodes (12
      manic and 15 depressed), and 43 periods of 1 month of euthymia. For the 60 days
      prior to episode or euthymia, the ApEn, linear statistics and the correlation
      between linear and non-linear measures were calculated. RESULTS: ApEn was
      significantly greater in the 60 days prior to a manic or depressive episode than
      the 60 days prior to a month of euthymia. The onset of an episode was associated
      with greater irregularity in mood. Variability was also significantly larger and
      correlated with ApEn. ApEn was significantly greater in the 60 days prior to a
      manic episode than in the 60 days prior to a depressed episode, whereas measures
      of variability were not significantly different. Mood in the 60 days prior to
      mania was more irregular than prior to depression. CONCLUSIONS: Non-linear
      measures may complement traditional linear measures in the analysis of
      longitudinal data in bipolar disorder. A larger study is indicated.

PMID- 17042881
TI  - Approximate entropy as a measure of irregularity for psychiatric serial metrics.
AB  - OBJECTIVES: The quantification of subtle patterns in sequential data, and their
      changes, has considerable potential utility throughout psychiatry, including the
      analyses of mood ratings, heart rate, respiratory, and electroencephalographic
      recordings. METHODS: Approximate entropy (ApEn), a relatively recently developed
      statistic quantifying serial irregularity, has been applied in numerous studies
      throughout mathematics and other fields of study, especially biology. RESULTS: We
      discussed applications of ApEn, both extant and potential, of most relevance to
      psychiatrists. We provided a mechanistic interpretation of lowered ApEn values,
      and discusses the relationship between ApEn and other (both classical and
      complexity) measures of serial dynamics. We also briefly discussed cross-ApEn, a
      thematically similar quantification of two-variable asynchrony that can aid in
      uncovering subtle disruptions in complicated network dynamics. CONCLUSIONS: ApEn
      and cross-ApEn have significant potential to consequentially enhance present
      statistical methodologies of analysis of psychiatric data, in both clinical and
      in research settings.

PMID- 17042882
TI  - Linear and nonlinear methods for analyses of cardiovascular variability in
      bipolar disorders.
AB  - OBJECTIVES: Heart rate variability (HRV), blood pressure variability (BPV), and
      the assessment of baroreflex sensitivity are widely accepted methods for
      analyzing and characterizing cardiovascular regulation and for an enhanced risk
      evaluation in different diseases. As a result of the complexity of the
      investigated regulatory systems, univariate analyses do not often provide a
      convenient description of pathological changes in the cardiovascular regulation.
      Therefore, the application of a multivariate approach is preferable. METHODS: We
      present principal methods of time-domain, frequency-domain, and nonlinear
      analyses of HRV, BPV as well as methods for coupling and interaction analyses.
      RESULTS: Changes in autonomic nervous system (ANS) tone are known to accompany
      various mental disorders. Depressive patients frequently complain of symptoms of
      ANS dysfunction, such as dry mouth, diarrhea, and insomnia. These clinical
      observations propose the assumption of altered autonomic dysfunction in these
      patients. In contrast to these clinical assumptions, inconsistent results have
      been found in studies of HRV in depressive patients. This work therefore covers a
      brief review of the literature in respect to bipolar disorder and the rationale
      to study autonomic changes in such a psychiatric disease. CONCLUSIONS:
      Prospective studies of cardiovascular changes in mania and depression are needed
      to evaluate a psychopathological state in connection with cardiovascular changes
      and cardiac morbidity and mortality. These studies should consider BPV, coupling
      and interaction analyses, the application of nonlinear methods, and a
      multivariate approach in addition to the traditional analysis of HRV.

PMID- 17042883
TI  - A novel technique to evaluate fluctuations of mood: implications for evaluating
      course and treatment effects in bipolar/affective disorders.
AB  - OBJECTIVES: Several psychiatric conditions are associated with frequent
      fluctuations of affect. In this study, we propose a new technique to uniformly
      score depression and mania objectively and use a new mathematical technique to
      model the frequent fluctuations in mood using simulated data. Our main aim is to
      examine the usefulness of this measure for evaluating treatment effects or course
      of illness, especially in bipolar or unipolar affective illness to quantify mood
      fluctuations. METHODS: We use a prototypical model, which takes into account the
      mean, the standard deviation (SD) and the coefficient of variation (CV =
      SD*100/mean) of the mood scores of the subjects over a user-defined period. We
      utilize simulated data of subjects for euthymia, minor depression, minor mania,
      severe depression, severe mania and cyclic bipolar illness (manic depression,
      MDP). We propose an objective method to quantify the mood of the subjects at
      weekly intervals (the interval can be user-defined) using a scale of 1-9 (1-4 =
      degrees of depression, 5 = euthymia, 6-9 = degrees of mania). These scores can be
      sampled according to the convenience and feasibility of the measurements, which
      can be derived from various clinical scales or by observation of the subjects in
      hospitals or other environments. We derive a new mathematical technique to arrive
      at a normalized measure for each of these conditions of simulated data in
      addition to the mean, SD and approximate entropy (ApEn). RESULTS: We utilize
      three sets of data, one to train the model to classify the condition of the
      subjects and the other two to test the reliability of the technique. We are able
      to successfully classify the condition of the subjects over a 52-timepoint period
      (length can be days or weeks depending upon the sampling rate). The New Index
      (NI) correlates significantly only with the mean (r(2) = 0.78), but not with the
      SD or ApEn score. CONCLUSIONS: These results indicate that it may be beneficial
      to reduce data according to the techniques we propose so that there is greater
      uniformity within which to compare future studies to evaluate treatment effects,
      not only in rapid-cycling MDP but also in other affective disorders. This method
      may be suitable for the meta-analysis of several studies, although different
      scales have been used in each of those studies. Our measure derived from
      simulated data has shown sufficient deviation of all the abnormal states from the
      euthymic state. The advantages and pitfalls of these techniques are further
      discussed to evaluate affect in various disorders. However, future prospective
      studies must address the importance of this measure in comparison with mean, SD
      and ApEn scores or other nonlinear measures of these time series. We are
      evaluating other nonlinear dynamic models, which may provide a continuous measure
      with which to identify different degrees of fluctuation of mood.

PMID- 17042884
TI  - Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in
      controlled studies of patients with bipolar mania.
AB  - OBJECTIVES: To evaluate extrapyramidal symptoms (EPS), including akathisia, with
      quetiapine in patients with bipolar mania. METHODS: Data were analyzed from four
      similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies
      evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n =
      198), with lithium or haloperidol monotherapy as respective active controls. Two
      studies evaluated quetiapine (up to 800 mg/day) in combination with a mood
      stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo
      and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were
      evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale
      (BARS), adverse event reports and anticholinergic drug usage. RESULTS: The
      incidence of EPS-related adverse events, including akathisia, was no different
      with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS
      related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO
      + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients
      treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated
      with lithium (n = 98) monotherapy experienced adverse events related to EPS. The
      incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and
      placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was
      associated with a significantly higher incidence (p < 0.05) of tremor (18.4%)
      than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of
      lithium, may have contributed to the elevated rate of tremor in patients
      receiving lithium therapy. Haloperidol induced a significantly higher incidence
      (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and
      extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant
      differences were observed between quetiapine and placebo on SAS and BARS scores.
      Anticholinergic use was low and similar with quetiapine or placebo. CONCLUSIONS:
      In bipolar mania, the incidence of EPS, including akathisia, with quetiapine
      therapy is similar to that with placebo.

PMID- 17042885
TI  - Pilot sample of very early onset bipolar disorder in a military population
      moderates the association of negative life events and non-fatal suicide attempt.
AB  - OBJECTIVE: To examine the moderating effects of very early onset diagnostic
      status (<or= 13 years) upon the association between life events and non-fatal
      suicide attempt. METHODS: Measures of negative life events, suicidal ideation and
      current suicide attempt were administered to 298 military-based young adults at
      entry to treatment for suicidality. Current and lifetime diagnoses were assigned
      using the Diagnostic Interview Schedule. The predictive ability of negative life
      events for non-fatal suicide attempt was examined separately for the total sample
      and for those with retrospectively determined histories of very early onset
      bipolar disorder (VEOBPD; n = 16), very early onset major depressive disorder
      (VEOMDD; n = 21) and very early onset anxiety disorder (VEOANX; n = 53). RESULTS:
      Negative life events and suicide attempt were significantly and positively
      associated among those with no history of VEOBPD (OR = 1.30, 95% CI = 1.02-1.65,
      p < 0.05), including those with VEOMDD and VEOANX. Consistent with expectation,
      VEOBPD moderated the association between negative life events and suicide attempt
      (OR = 0.88, 95% CI = 0.78-0.99, p < 0.05), such that negative life events were
      non-significantly and negatively associated with the presence of a suicide
      attempt (OR = 0.21, 95% CI = 0.04-1.02, p = 0.09) among patients with a history
      of VEOBPD. CONCLUSIONS: Despite similar rates of suicide attempt among all
      diagnostic groups, life stress did not contribute to attempt among those with
      VEOBPD. These findings are consistent with the severity and chronicity of VEOBPD.
      Potential explanations of these findings include a scarring effect on coping
      skills and increased sensitization to life stress.

PMID- 17042886
TI  - Allopurinol as an adjunct to lithium and haloperidol for treatment of patients
      with acute mania: a double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: Allopurinol, a hypouricemic agent, has been shown to present
      therapeutic effects in mania associated with hyperuricemia. This study assessed
      the efficacy and safety of risperidone as an adjunctive agent to lithium and
      haloperidol for the treatment of acute mania in hospitalized bipolar patients.
      METHODS: Eighty-two patients aged between 18 and 49 were eligible to participate,
      as they met the DSM-IV criteria for a current manic episode, on the basis of a
      clinical interview by two academician psychiatrists. In addition, a score of at
      least 20 points on the Young Mania Rating Scale was required representing at
      least a moderate-to-severe mania. Forty-one patients were randomly allocated to
      lithium (1-1.2 mEq/L) + haloperidol (10 mg/day) + allopurinol (300 mg/day) (group
      A) or lithium (1-1.2 mEq/L) + haloperidol (10 mg/day) + placebo (group B) for an
      8-week, double-blind, placebo-controlled study. Patients were assessed by a third
      year resident of psychiatry at baseline and at 7, 14, 28, 42, and 56 days after
      the medication started. The mean decrease in the Young Mania Rating Scale score
      from baseline was used as the main outcome measure of response of mania to
      treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal
      Symptoms Rating Scale (ESRS). Side effects were systematically recorded
      throughout the study and were assessed using a checklist. RESULTS: Young Mania
      Rating Scale scores improved with allopurinol. The difference between the two
      protocols was significant as indicated by the effect of the group, the between
      subjects factor (F = 5.22, df = 1, p = 0.008). The mean ESRS scores for the
      placebo group were higher than the allopurinol group. However, the differences
      were not significant over the trial. The difference between the two groups in the
      frequency of side effects was not significant except for agitation that was more
      often in the placebo group. CONCLUSIONS: The efficacy of allopurinol to obtain a
      greater improvement in patients with mania seems to support the purinergic
      dysfunction in mania.

PMID- 17042887
TI  - Association study of 5'-UTR polymorphisms of the human dopamine transporter gene
      with manic depression.
AB  - OBJECTIVES: To determine the degree of association of five single nucleotide
      polymorphisms at the 5'-untranslated region (5'-UTR) of the human dopamine
      transporter gene (hSLC6A3; hDAT1) in bipolar affective disorder. METHODS: In a
      case-control design study, the polymorphisms were genotyped for allelic and
      genotypic distribution between 105 index cases (50 males) with bipolar affective
      disorder according to DSM IV and 199 unaffected control subjects (120 males).
      RESULTS: At the 5'-UTR locus of hSLC6A3, no significant allelic or genotypic
      differences were observed between index cases and controls. However, distinct 5
      locus genotypes accumulated in subjects with bipolar affective disorder compared
      to control subjects (p = 0.029, odds ratio 1.84, 95% confidence interval 1.12
      3.02). CONCLUSIONS: In conclusion, our data do not provide evidence for a major
      role of the 5'-UTR of the dopamine transporter gene in bipolar affective
      disorder. A minor contribution of distinct genotypes may be possible and warrants
      replication in extended samples.

PMID- 17042888
TI  - Aggression and substance abuse in bipolar disorder.
AB  - OBJECTIVES: The goal of this retrospective study was to examine factors
      differentiating persons with bipolar disorder who did or did not have comorbid
      lifetime substance use disorders (SUD) at an index assessment. We also explored
      the chronology of onset of mood and SUD. METHODS: We studied 146 subjects with
      DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were
      compared on demographic and clinical measures. RESULTS: Substance abuse disorders
      in this bipolar sample were associated with male sex, impulsive-aggressive
      traits, comorbid conduct and Cluster B personality disorders, number of suicide
      attempts and earlier age at onset of a first mood episode. In a multivariable
      logistic regression analysis, male sex and aggression and possibly earlier age at
      mood disorder onset were associated with SUD. In those with or without SUD, the
      first mood episode tended to be depressive and to precede the onset of SUD.
      CONCLUSIONS: In persons with bipolar disorder, an earlier age of onset and
      aggressive traits appear to be factors associated with later development of
      comorbid SUD.

PMID- 17042889
TI  - Carnitine does not improve weight loss outcomes in valproate-treated bipolar
      patients consuming an energy-restricted, low-fat diet.
AB  - OBJECTIVES: Carnitine deficiency impairs fatty acid beta-oxidation and may partly
      explain weight gain in valproate-treated patients. The aim of this study was to
      determine whether l-carnitine supplementation improves weight loss outcomes in
      bipolar patients taking sodium valproate. METHODS: Sixty bipolar patients with
      clinically significant weight gain thought to be related to sodium valproate, who
      had been taking sodium valproate for >or=6 months, were randomized to l-carnitine
      (15 mg/kg/day) or placebo for 26 weeks, in conjunction with a moderately energy
      restricted, low-fat diet. The primary outcome measure was weight change. RESULTS:
      l-carnitine had no effect on mean weight loss compared with placebo (-1.9 kg
      versus - 0.9 kg) (F = 0.778, df = 1,58, p = 0.381). The number of people in each
      group able to lose any weight was identical ( = 0, p = 1.0); more patients in the
      carnitine group (nine versus five) achieved a clinically significant weight loss
      (>or=5%) but this was not statistically significant (p = 1.0, Fisher's exact
      test). CONCLUSIONS: At the dose prescribed in this study carnitine
      supplementation did not improve weight loss outcomes in valproate-treated bipolar
      patients consuming an energy-restricted, low-fat diet.

PMID- 17042890
TI  - Cognitive-behavioral therapy for bipolar disorders in adolescents: a pilot study.
AB  - OBJECTIVES: To develop a cognitive behavioral intervention for adolescents with
      bipolar disorders, test its feasibility and preliminary efficacy. METHODS: Based
      on existing research, a manualized, individually delivered cognitive behavioral
      intervention was developed and tested with adolescents with bipolar disorders as
      an adjunct to pharmacological treatment. Using existing data, baseline
      characteristics and outcome were compared to a matched group of eight adolescents
      with bipolar disorders who did not receive any psychosocial intervention.
      RESULTS: Preliminary results support the feasibility and efficacy of this
      manualized cognitive behavioral intervention. CONCLUSIONS: Individually delivered
      cognitive-behavioral therapy (CBT) as an adjunct to pharmacological treatment is
      feasible and associated with symptom improvement in adolescents with bipolar
      disorders. Randomized controlled studies are needed.

PMID- 17042891
TI  - Aromatase inhibitors and bipolar mood disorder: a case report.
AB  - OBJECTIVE: To report a case in which the aromatase inhibitor letrozole produced
      irritable mood elevation followed by depression in a woman with a history of
      postpartum depression. METHODS: A 60-year-old Caucasian woman who had a severe
      depressive episode after the birth of her only child, 32 years earlier, was
      treated successively with anastrozole and letrozole following a mastectomy,
      radiotherapy and chemotherapy. RESULTS: Mrs X was prescribed anastrozole for
      about 6 weeks. During this time she experienced labile mood, increased activity,
      tremulousness and difficulty sleeping. These symptoms disappeared after stopping
      the anastrozole. On letrozole, she developed an acute irritable activated mood
      elevation, which then subsided into a prolonged major depression after withdrawal
      of letrozole. These effects occurred during co-prescription of amitriptyline at a
      low dose for urinary frequency. CONCLUSIONS: The present case suggests caution
      may be warranted when employing aromatase inhibitors, especially in women with a
      past history of postpartum affective disorder or bipolar disorder. As with
      postpartum mania, the primary mechanism of the effect may be acute reduction in
      circulating oestrogen levels.

PMID- 17042892
TI  - Re-evaluation of randomized controlled trials of lithium monotherapy.

PMID- 17042895
TI  - Exercise capacity and cardiovascular changes in patients with beta-thalassaemia
      major.
AB  - Despite the introduction of deferoxamine, 50% of thalassaemia major patients die
      before the age of 35 years predominantly from iron induced heart failure. Indeed,
      the assessment of myocardial performance may be of particular interest since it
      can reveal an early myocardial dysfunction. By using impedance cardiography and
      mass spectrometry, we studied the cardiac function and the oxygen extraction
      ratio (O(2)ER) of 14 thalassaemic patients and 15 control healthy subjects during
      an incremental cycle-ergometer test. The achieved mechanical power output and the
      relative O(2) uptake did not reach any significant difference between groups. At
      the highest workload, O(2)ER reached significantly higher values in thalassaemic
      patients versus control subjects while the relationship between cardiac index
      (CI) and O(2)ER (CI/O(2)ER) decreased showing a lower contribution of
      cardiovascular system to maintain O(2) uptake. Results of this study imply that
      CI/O(2)ER allows an early diagnosis of the iron induced myocardial dysfunction,
      whereas it is not clinically patent yet. To our knowledge, this is the first
      study revealing an O(2)ER pivotal role as compensatory mechanism to maintain a
      normal working capacity in subjects suffering from thalassaemia major.

PMID- 17042896
TI  - Supraorbital cutaneous blood flow rate during carotid endarterectomy.
AB  - BACKGROUND: The supraorbital skin region is supplied by the supraorbital artery,
      which is a branch of the internal carotid artery. The supraorbital cutaneous
      blood flow rate may therefore be influenced by changes in the internal carotid
      artery flow during carotid endarterectomy. METHODS: The supraorbital cutaneous
      blood flow rate was measured by the application of heat to the skin and following
      the subsequent dissipation of the heat in seven patients undergoing carotid
      endarterectomy. At the same time, the oxygenation in the right and left frontal
      region was monitored by near-infrared spectroscopy (NIRS). RESULTS: During cross
      clamping of the carotid artery, the ipsilateral NIRS-determined frontal
      oxygenation tended to decrease [67 +/- 13% to 61 +/- 11% (P = 0.06);
      contralateral 68 +/- 11% to 66 +/- 8%] as did the supraorbital cutaneous blood
      flow rate from 56 +/- 23 to 44 +/- 7 ml 100 g(-1) min(-1). With the opening of
      the external carotid artery, the NIRS-determined frontal oxygenation reversed to
      66 +/- 8% (P<0.05) on the ipsilateral side, with no significant change on the
      contralateral side and the supraorbital cutaneous blood flow rate increased to 53
      +/- 11 (P<0.05). Opening of the internal carotid artery did not significantly
      affect the NIRS (67 +/- 8% and 69 +/- 9%; ipsilateral, contralateral), but the
      supraorbital cutaneous blood flow rate increased to 88 +/- 10 ml 100 g(-1) min(
      1) (P<0.001). CONCLUSION: Cross-clamping of the internal carotid artery affects
      the supraorbital cutaneous blood flow rate as well as the frontal lobe
      oxygenation.

PMID- 17042898
TI  - Signal quality in a three-channel ambulatory electrocardiographic monitoring
      system.
AB  - BACKGROUND: Ambulatory electrocardiographic recordings are not infrequently
      hampered by technical artefacts. Verification of good original signal level and
      an adequate number of ECG channels should enhance the quality. METHODS: Data from
      all three-channel (mV5, mV1, III) recordings in Peijas hospital during one
      calendar year were prospectively collected. A total of 255 recordings (24 h n =
      239, and 48 h n = 16) made for 247 patients were analysed. Relative signal
      strength number (integer scale 5-0) was registered during hook-up. Final quality
      of recordings were afterwards evaluated with a three-point semi-quantitative
      scale by an experienced physician. RESULTS: The signal strength number was
      adequate (>or=3) in all 241 available cases. Distribution of signal strength did
      not significantly vary between ECG channels. The overall quality of recordings
      was 'good' in three-fourth of the cases and only were they seldom 'poor'. Signal
      strength and quality ratings were not significantly interrelated. The quality
      was, as expected, better in 24 h recording than in 48 recordings, and it was also
      better in channel III than in channel mV5. CONCLUSIONS: The original signal
      strength level (impedance) is not a crucial fact in ambulatory
      electrocardiographic recordings as long as it is within (specified) acceptable
      limits. In terms of quality, a third (inferior) ECG channel is recommendable.

PMID- 17042897
TI  - Effect of adrenergic blockade on plasma adrenomedullin concentration during
      static handgrip in patients with heart failure.
AB  - Our previous study showed that static handgrip caused increases in the plasma
      adrenomedullin (ADM) both in patients with heart failure (HF) and healthy
      subjects. The present study was designed to determine the role of the sympathetic
      nervous system in mediating plasma ADM changes during handgrip in patients with
      HF. Twelve male HF patients (II class NYHA) treated with carvedilol, a non
      selective adrenergic blocker (TC) and 12 patients untreated with carvedilol (UC)
      performed two 3-min bouts of static handgrip at 30% of maximal voluntary
      contraction, alternately with each hand. At the end of both exercise bouts and in
      5 min of the recovery period, plasma ADM and catecholamines were determined. In
      addition, heart rate, blood pressure and stroke volume (SV) were measured. The
      baseline plasma ADM, noradrenaline (NA) and adrenaline (A) levels were similar in
      the two groups of patients, while SV was higher (P<0.05) in TC than in UC. During
      exercise plasma ADM concentrations were lower (P<0.05) in TC than in UC, but the
      handgrip-induced increases in plasma ADM did not differ between the groups.
      Plasma ADM correlated with NA concentrations (r = 0.764) and with SV (r = -0.435)
      and increases in plasma ADM expressed as percentage of baseline values correlated
      with those of plasma NA (r = 0.499), diastolic BP (r = 0.550) and total
      peripheral resistance (r = 0.435). The study suggests that the sympathetic
      nervous system may be involved in the stimulation of ADM secretion during static
      exercise either directly or by changes in the haemodynamic response.

PMID- 17042899
TI  - Pre- and postoperative evaluation of the metabolic activity in muscles associated
      with ruptured rotator cuffs by F-FDG PET imaging.
AB  - We examined uptake of 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) using positron
      emission tomography (PET) into the bilateral shoulder muscles of four patients
      before and after unilateral rotator cuff repair. The relative ratio of the
      subtracted standardized uptake value on the supraspinatus with a torn
      supraspinatus tendon to that of the subscapularis on the ipsilateral side was
      significantly lower than that on the normal side (0.69 +/- 0.05 versus 1.06 +/-
      0.36). The relative ratio of the infraspinatus on the rupture side was also
      significantly lower than that on the normal side (0.91 +/- 0.09 versus 1.41 +/-
      0.35). However, by 6 months postoperative, the reduced glucose metabolism in
      these muscles had recovered to the same levels as those on the normal side. As
      indicated by FDG PET, muscle metabolism in rotator cuff tears was reduced,
      subsequently recovering to the level of the normal side after operative repair.

PMID- 17042900
TI  - Subendocardial versus transmural ischaemia in myocardial perfusion SPECT--a Monte
      Carlo study.
AB  - Myocardial perfusion imaging with single-photon emission computed tomography
      (SPECT) is useful for the evaluation of patients with known or suspected coronary
      artery disease. Parameters of interest are the reduction in the blood perfusion
      (severity) and the lesion volume (extent). The aim of this study was to evaluate
      these parameters, as calculated by automatic quantification software, for
      different cases of subendocardial and transmural myocardial lesions. METHODS: A
      computer phantom was used to simulate 32 male patients with different defect
      locations and activity uptakes, which were based on clinical patient studies. The
      Monte Carlo program SIMIND was used to simulate realistic SPECT projections which
      were reconstructed to give short-axis images, analysed by the AutoQUANT program
      using the same procedure as for a real patient. RESULTS: The results showed a
      disparity between the quantification of transmural and subendocardial lesions
      with the same lesion activity uptake reduction and this could be confirmed by
      visual interpretation. Neither the parameters given by the quantification program
      nor visual interpretation could distinguish between the transmural lesions and
      the subendocardial lesions with activity uptake reduction twice as high as in the
      corresponding transmural lesions. CONCLUSION: Transmural lesions and the
      corresponding subendocardial lesions with the same activity uptake reduction
      could be separated by the quantification software for SPECT imaging and visual
      analysis. The subendocardial lesions with activity uptake reduction twice as high
      as in the corresponding transmural lesions could not be differentiated neither by
      the quantification software nor by visual interpretation. Thus these lesions will
      get the same scoring when analysed by the AutoQUANT program.

PMID- 17042901
TI  - Acute administration of a single dose of valsartan improves left ventricular
      functions: a pilot study to assess the role of tissue velocity echocardiography
      in patients with systemic arterial hypertension in the TVE-valsartan study I.
AB  - BACKGROUND: The advent of colour-coded tissue velocity echocardiography (TVE) has
      now made it possible to quantify left ventricular (LV) functions in patients with
      systemic arterial hypertension (HTN). Hypothesis In this project, we have studied
      the cardiac effects of a single dose of orally administered valsartan in patients
      with known HTN. METHODS: Fifty-five patients with HTN with a mean age of 56 +/-
      10 years were given an early morning dose of 80 mg valsartan withholding regular
      antihypertensive medications on the day of investigation. TVE images, acquired on
      VIVID systems were digitized for postprocessing of longitudinal and radial peak
      systolic velocities, strain rate, and systolic and diastolic time intervals
      before (pre) and 5 h after (post) administration of the drug. RESULTS: Blood
      pressure (mmHg) pre and post, respectively, were 147 +/- 15 versus 137 +/- 14
      systolic and 90 +/- 7 versus 86 +/- 7 diastolic (all P<0.01). LV longitudinal
      systolic velocities (cm s(-1)) were significantly higher post in LV septum (5.7
      +/- 1.1 versus 6.4 +/- 1.6; P<0.001) with similar results obtained in other LV
      walls. Radial strain rate (1 s(-1)) was significantly higher post compared with
      pre valsartan (2.1 +/- 0.6 versus 2.3 +/- 0.9; P<0.01). Regional diastolic
      filling and ejection times (ms) were significantly shorter post (390 +/- 122
      versus 370 +/- 120 and 275 +/- 32 versus 163 +/- 36 respectively; all P<0.05).
      CONCLUSIONS: Within 5 h after oral administration of valsartan, improvement in
      regional myocardial systolic functions could be registered. Although the changes
      could well be secondary to afterload reduction, additional effects of the drug,
      evidenced by improved strain rate that is relatively load-independent, may have
      contributed in this improvement.

PMID- 17042902
TI  - Surfactant as a carrier: influence of immunosuppressive agents on surfactant
      activity.
AB  - INTRODUCTION: It has been proposed that exogenous pulmonary surfactant can be
      used as a drug delivery system for immunosuppressive agents to the alveolar
      compartment of the lung while reducing the risk of systemic toxicity. Before
      using this combination, however, alterations in activity of both substances
      should be examined. Therefore, this study investigated whether the activity of a
      natural derived surfactant preparation is changed after it is mixed with
      cyclosporine A (CsA) or rapamycin (RPM). METHODS: A surfactant suspension was
      mixed with CsA or RPM and minimal surface tension of these mixtures was measured
      in vitro. Surfactant activity was evaluated in vivo by its capacity to restore
      gas exchange in an established model of surfactant deficiency in rats. CsA
      surfactant, RPM-surfactant or surfactant alone was instilled intratracheally and
      blood gases were measured under standardized ventilatory conditions. RESULTS:
      Minimal surface tension of surfactant-CsA was comparable with that of surfactant
      alone, whereas minimal surface tension of the surfactant-RPM mixture was
      increased. In vivo partial arterial oxygen pressure levels increased immediately
      to prelavage values after instillation of CsA-surfactant, RPM-surfactant and
      surfactant only and were comparable during the entire study period. CONCLUSION:
      The activity of a naturally derived surfactant was affected when mixed with RPM
      but not when mixed with CsA at the used concentrations.

PMID- 17042903
TI  - Non-dipolar content of the T-wave as a measure of repolarization inhomogeneity in
      ST-elevation myocardial infarction.
AB  - The non-dipolar content of the T-wave, i.e. the component of the signal, which
      cannot be explained by a dipolar model, has been suggested as a measure of the
      local repolarization inhomogeneity. Our purpose was to study the non-dipolar
      content of the T-wave during the initial course of ST-elevation myocardial
      infarction (STEMI), when local repolarization inhomogeneity presumably is
      markedly increased. Twelve-lead ECG was semicontinuously collected in 211
      patients with STEMI, treated with a thrombolytic agent. The T-wave was processed
      by principal component analysis. The absolute and relative T-wave residues were
      used as measures of the non-dipolar content. The median values for each hour and
      for the entire monitoring time were computed. Changes in the parameters were
      closer studied in two windows, 0-10 respectively, 11-24 h after start of ECG
      monitoring. The median of the absolute T-wave residue during the entire
      monitoring period was 25 000 units in the STEMI-group and 13 500 units in the
      comparison group. The median for hour 1 was 36 500 units and 28 800 units for
      hour 2. The decrease was greater in patients with >or=50% resolution of the ST
      elevation at 60 min. The moment of change, identified by cumulative sum-method,
      showed no correlation to the time for 50% ST-resolution. We conclude, that
      patients with thrombolysed STEMI have an increased non-dipolar content of the T
      wave. Resolution of the ST-elevation is associated with a decrease. The increased
      non-dipolar content reflects a property of the repolarization phase, which is
      related to but separated from the ST-elevation.

PMID- 17042904
TI  - Liver-type fatty acid binding protein in serum and broncho-alveolar lavage in a
      model of acute respiratory failure because of surfactant depletion--a possible
      marker for lung damage?
AB  - INTRODUCTION: Liver-type fatty acid binding proteins (L-FABP) have been shown to
      be present in alveolar macrophages and type II pneumocytes of the lung. This
      study determined levels of L-FABP in serum and broncho-alveolar lavage (BAL)
      during experimental acute respiratory failure (ARF) to evaluate whether this
      molecule can serve as a marker for lung damage. METHODS: Male Sprague-Dawley rats
      (n = 24) were ventilated and either lung lavaged or lavaged and treated with
      surfactant, and compared to ventilated, non-lavaged controls. Blood samples were
      drawn every hour for 4 h to measure L-FABP concentrations in serum. At the end of
      the experiment a BAL was performed to determine L-FABP levels in BAL fluid. L
      FABP was measured with a sandwich enzyme-linked immunosorbent assays. RESULTS:
      Serum L-FABP concentrations rose significantly during the first 2 h of
      ventilation in all groups compared with baseline values. After 2 h L-FABP levels
      were significantly higher in lavaged animals compared with the ventilated
      controls and to animals treated with surfactant. After 4 h of ventilation, L-FABP
      in BAL was significantly higher in lavaged, non-surfactant treated animals
      compared with the ventilated controls. CONCLUSION: In the early phase of
      experimental ARF serum L-FABP levels correlate well with the degree of lung
      injury.

PMID- 17042905
TI  - Early recovery from post-traumatic acute respiratory distress syndrome.
AB  - BACKGROUND: To present and discuss the rationale and possible benefits of timely
      alveolar recruitment in early post-traumatic acute respiratory distress syndrome.
      METHODS: A 17-year-old patient who had sustained blunt thoracic trauma presented
      with severe hypoxaemia on admission and whole body computed tomography showed
      pulmonary contusion and substantial bilateral atelectasis. Oxygenation and lung
      mechanics did not improve with low tidal volume ventilation using high positive
      end-expiratory pressures (PEEPs). Therefore we applied an alveolar recruitment
      manoeuvre 7 h after admission. After alveolar recruitment, PEEP was titrated to
      the lowest level which prevented alveolar derecruitment. RESULTS: Oxygenation and
      lung compliance improved rapidly and aeration of the entire lung was confirmed by
      computed tomography 27 h after the recruitment manoeuvre. The patient recovered
      completely and was discharged after 17 days. CONCLUSION: Although robust evidence
      is still lacking, several lines of evidence suggest potential benefits of timely
      alveolar recruitment. Patients with early post-traumatic respiratory failure seem
      to most readily respond to alveolar recruitment manoeuvres and could thus benefit
      from the gain in functional lung volume and oxygenation. Moreover the probability
      of ventilator associated complications may be reduced.

PMID- 17042906
TI  - The acute effects of different whole body vibration amplitudes on the endocrine
      system of young healthy men: a preliminary study.
AB  - Whole body vibration (WBV) has been suggested as an alternative form of exercise
      producing adaptive responses similar to that of resistance training. Very limited
      information is available on the effects of different vibration parameters on
      anabolic hormones. In this study, we compared the acute effects of different WBV
      amplitudes on serum testosterone (T) and insulin growth factor-1 (IGF-1). Nine
      healthy young recreationally active adult males (age 22 +/- 2 years, height 181
      +/- 6.3 cm, weight 77.4 +/- 9.5 kg) voluntarily participated in this randomized
      controlled (cross-over design) study. The subjects performed 20 sets of 1 min
      each of WBV exercise in the following conditions: Non-vibration condition
      (control), low amplitude vibration [low (30 Hz, 1.5 mm peak-to-peak amplitude)]
      and high amplitude vibration [high (30 Hz, 3 mm peak-to-peak amplitude)]. Blood
      samples were collected before, after 10 sets, at the end (20th set) and after 24
      h of the exercise bout. WBV exercise did not produce significant changes in serum
      T and IGF-1 either with low or high amplitude when compared with the control
      condition. The results of this study demonstrate that a single session of WBV
      exposure with a frequency of 30 Hz and amplitudes of 1.5 and 3 mm does not
      noticeably alter serum T and IGF-1 levels.

PMID- 17042907
TI  - Phenotyping the level of blood pressure by telemetry in mice.
AB  - 1. Using telemetry, arterial blood pressure (BP) can be measured directly over
      long periods in freely behaving animals without recent anaesthesia or surgery. In
      the present review, we discuss the strengths and limitations of this method and
      important considerations in using the method to characterize the BP level in
      mice. 2. A variety of informative statistics can be used to describe the BP level
      and we have made available a spreadsheet template for their calculation on a
      routine basis. The BP level is well summarized using the average value for an
      entire 24 h period or for the individual light and dark phases of the day. Such
      long-term averages exhibit less statistical variation than those of short
      recording periods. In addition, averages of the dark and light phases of the day
      convey information concerning circadian variations of BP. 3. The frequency
      distribution of BP samples provides additional information concerning the range
      of BP values recorded over the course of the day and can be described in terms of
      percentiles of the distribution that correspond with the minimum and maximum BP
      values and their span. 4. In mice, BP can be markedly affected by locomotor
      activity cycles that occur frequently throughout both the light and dark phases
      of the day. In addition, BP is strongly affected by ambient temperature and food
      intake, as well as potentially by other determinants of energy balance.
      Consideration of these factors may help improve accuracy and precision when
      phenotyping the BP level in mice.

PMID- 17042908
TI  - Comparison of the effects of tulobuterol patch and salmeterol in moderate to
      severe asthma.
AB  - 1. Although the clinical effects of the tulobuterol patch have been reported to
      include an increase in morning peak expiratory flow (PEF) values and a decrease
      of symptoms and the frequency of the rescue use of inhaled short-acting beta2
      adrenoceptor agonists, no trials comparing the efficacy of the tulobuterol patch
      to other standard inhaled long-acting beta2-adrenoceptor agonists have yet been
      conducted. The aim of the present study was to compare the clinical effects of
      the patch formulation of tulobuterol with those of inhaled salmeterol in moderate
      to severe asthma. 2. Fifty-four patients with moderate to severe asthma, whose
      conditions were suboptimally controlled despite receiving inhaled
      corticosteroids, were recruited. The study was a prospective, randomized trial of
      cross-over design comparing the effects of 4 weeks treatment with tulobuterol
      patch, 2 mg once daily, and salmeterol, 50 mg twice daily. The mean
      prebronchodilator morning PEF during the last 14 days of each treatment period
      and health-related quality of life (HRQoL) were the primary outcome variables.
      The HRQoL was assessed using the St George's Respiratory Questionnaire. 3. Forty
      four patients (81.5%) completed the trial and were included in the analysis. The
      mean morning PEF and HRQoL score were significantly improved in both the
      salmeterol (P < 0.0001 and P < 0.05, respectively) and the tulobuterol patch (P <
      0.01 and P < 0.05, respectively) treatment periods compared with the run-in
      period. Although the mean morning PEF was significantly higher in the salmeterol
      treated group than in the tulobuterol-treated group (P < 0.001), the HRQoL scores
      were comparable. 4. The tulobuterol patch may be useful as a controller
      medication in addition to inhaled corticosteroids in moderate to severe asthma.

PMID- 17042909
TI  - Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress
      in experimental diabetic neuropathy.
AB  - 1. Diabetic neuropathy is one of the most common complications of diabetes and
      oxidative stress has been implicated to play a major role in its pathophysiology.
      2. In the present study, we targeted oxidative stress using trolox, an anti
      oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. Compared with
      control rats, diabetic rats showed significant deficits in motor nerve conduction
      velocity (MNCV; 49.91 +/- 1.94 vs 42.77 +/- 1.39 m/s, respectively) and nerve
      blood flow (NBF; 107.98 +/- 8.22 vs 38.9 +/- 2.7 arbitarary perfusion units,
      respectively) after 8 weeks of diabetes. Tail flick latencies for cold and hot
      immersion tests were also significantly reduced in diabetic rats, indicating
      thermal hyperalgesia. These observations indicate development of diabetic
      neuropathy. 4. A significant decrease in the activity of anti-oxidant enzymes
      (superoxide dismutase and catalase) and an increase in lipid peroxidation were
      observed in sciatic nerves from diabetic rats compared with age-matched control
      rats. Alterations in the activity of anti-oxidant enzymes and lipid peroxidation
      in diabetic rats indicate oxidative stress in diabetic neuropathy. 5. Two weeks
      treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th
      week of diabetes significantly improved MNCV, NBF and inhibited thermal
      hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes
      and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The
      results of the present study suggest the beneficial effects of trolox in
      experimental diabetic neuropathy.

PMID- 17042910
TI  - Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the
      rat.
AB  - 1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial
      dysfunction associated with nitric oxide (NO) deficiency and increased superoxide
      (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have
      been reported to improve endothelial function through increased availability of
      NO and reduced O2- production in various forms of hypertension. In the present
      study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent
      endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague
      Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were
      treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days.
      Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in
      Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood
      pressure (SBP) was measured on alternate days using the tail-cuff method.
      Endothelial function was assessed by acetylcholine-induced vasorelaxation and
      phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was
      assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3.
      In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2
      mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP
      was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P <
      0.001), but was significantly lower than SBP in the group treated with Dex alone
      (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were
      greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P <
      0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato
      group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment
      with Ato improved endothelial function, reduced superoxide production and reduced
      SBP in Dex-treated SD rats.

PMID- 17042911
TI  - Edaravone reduces myocardial infarct size and improves cardiac function and
      remodelling in rabbits.
AB  - 1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2
      pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI)
      size and cardiac function in an in vivo model of MI in rabbits. We further
      investigated the contribution of hydroxyl radicals, superoxide and nitric oxide
      (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were
      subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n
      = 10) was injected with saline 10 min before reperfusion. The edaravone group (n
      = 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion.
      The edaravone + N(G)-nitro-L-arginine methyl ester (L-NAME) group (n = 5) was
      given 10 mg/kg, i.v., L-NAME 10 min before the administration of 3 mg/kg
      edaravone. The L-NAME group (n = 5) was given 10 mg/kg, i.v., L-NAME 20 min
      before reperfusion. Infarct size was measured using the triphenyl tetrazolium
      chloride method and is expressed as a percentage of area at risk. Cardiac
      function was assessed by echocardiography 14 days after infarction. 3. In another
      series of experiments, rabbits were subjected to 30 min coronary occlusion and 30
      min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and
      2,5-DHBA levels, indicators of hydroxyl radical, were measured using a
      microdialysis technique. 4. Infarct size in the edaravone group was significantly
      reduced compared with that in the control group (27.4 +/- 6.8 vs 43.4 +/- 6.8%,
      respectively; P < 0.05). The edaravone-induced reduction of infarct size was
      abolished by pretreatment with L-NAME. Myocardial interstitial levels of 2,3-DHBA
      and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min
      reperfusion in the control group. Edaravone significantly inhibited the increase
      in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining
      showing in situ detection of superoxide was less intense in ischaemic myocardium
      in the edaravone-treated group compared with the control group. Edaravone
      improved cardiac function and left ventricular remodelling 14 days after
      infarction. 5. In conclusion, edaravone significantly reduces MI size and
      improves cardiac function and LV remodelling by decreasing hydroxyl radicals and
      superoxide in the myocardium and increasing the production of NO during
      reperfusion in rabbits.

PMID- 17042912
TI  - D-dopa is unidirectionally converted to L-dopa by D-amino acid oxidase, followed
      by dopa transaminase.
AB  - 1. Many studies have shown that administration of d-3, 4-dihydroxyphenylalanine
      (D-dopa) produces contralateral rotation in hemi-parkinsonian animals comparable
      to L-dopa, with less potency and slower onset. It was postulated that D-dopa was
      converted to L-dopa to produce these effects. 2. To investigate the postulated
      chiral inversion of D-dopa to L-dopa and the related mechanism, an enantiomeric
      separation method for D- and L-dopa using HPLC was first established. Then, rat
      kidney homogenates containing D-dopa or L-dopa were incubated and subjected to
      HPLC to detect traces of respective enantiomer generation. The mechanism of the
      chiral inversion of d-dopa was explored by direct measurement of the production
      of L-dopa in kidney homogenates. D-dopa incubations containing different
      concentrations of an inhibitor of D-amino acid oxidase (DAAO) and an inhibitor of
      dopa transaminase were measured for L-dopa generation using HPLC. The role of
      DAAO in the chiral inversion of D-dopa to L-dopa was further investigated by
      using purified DAAO and mutant ddY/DAAO- mouse kidney lacking DAAO activity. 3.
      In rat kidney homogenate, D-dopa was, indeed, converted to L-dopa, whereas L-dopa
      was not converted to D-dopa. Sodium benzoate, a selective inhibitor of DAAO,
      blocked L-dopa generation in a concentration-dependant manner. In contrast with
      kidney homogenates of wild-type ddY/DAAO+ mice, those of mutant ddY/DAAO- mice
      lacking DAAO activity did not convert D-dopa to L-dopa unless exogenous DAAO
      protein was added. Conversely, when carbidopa, an inhibitor of dopa transaminase,
      was added to the homogenates, significant inhibition of L-dopa production was
      noted. 4. These results prove the proposal that d-dopa undergoes unidirectional
      chiral inversion and further suggest that D-dopa is first oxidatively deaminated
      by DAAO to its alpha-keto acid and then transaminated by dopa transaminase to L
      dopa.

PMID- 17042913
TI  - Sertraline protects against monocrotaline-induced pulmonary hypertension in rats.
AB  - 1. Serotonin (5-HT), as a type of mitogen for smooth muscle cells, plays an
      important role in the development of pulmonary hypertension. It is known that
      selective serotonin re-uptake inhibitors (SSRI) inhibit 5-HT internalization.
      Therefore, the aim of the present study was to investigate the protective effect
      and mechanism of the SSRI sertraline against pulmonary hypertension. 2.
      Monocrotaline (MCT)-induced chronic 'inflammatory' pulmonary hypertension in
      Wistar rats was established. Pulmonary haemodynamic measurement and lung tissue
      morphological investigations were undertaken. Serotonin transporter (SERT) mRNA
      was assayed by reverse transcription-polymerase chain reaction (RT-PCR). 3. The
      results showed that pulmonary artery pressure (PAP) was significantly increased
      by MCT treatment from 12.6 +/- 2.1 to 20.1 +/- 3.4 mmHg (P < 0.01 vs control) and
      sertraline attenuated the MCT-induced increase in PAP from 20.1 +/- 3.4 to 16.4
      +/- 1.8 mmHg (P < 0.05 vs MCT). The right ventricular index was increased in the
      MCT-treated group from 0.32 +/- 0.04 to 0.51 +/- 0.09 (P < 0.01 vs control) and
      was reduced to 0.42 +/- 0.04 by sertraline (P < 0.05 vs MCT). The degree of
      muscularization of the pulmonary artery in the MCT-treated group was
      significantly higher than control (P < 0.01) and was decreased by sertraline (P <
      0.01 vs MCT). The RT-PCR assay showed that MCT increased SERT mRNA expression
      from 0.86 +/- 0.08 to 0.99 +/- 0.06 (P < 0.05 vs control), which was attenuated
      by sertraline (0.82 +/- 0.09; P < 0.05 vs MCT). 4. In conclusion, the SSRI
      sertraline protects against MCT-induced pulmonary hypertension by decreasing PAP,
      right ventricular index and pulmonary artery remodelling, which may be related to
      a reduction in SERT mRNA.

PMID- 17042914
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces
      infarction volume and neurological deficits in an embolic model of stroke.
AB  - 1. Stroke is accompanied by a robust inflammatory response, glutamate-mediated
      excitotoxicity, release of reactive oxygen species and apoptosis.
      Thiazolidinediones, which target the nuclear receptor peroxisome proliferator
      activated receptor (PPAR)-g, have been reported recently to exhibit potent anti
      inflammatory and anti-oxidant actions and inhibit both neural excitotoxicity and
      apoptosis. 2. The present study was conducted to determine whether rosiglitazone,
      a potent thiazolidinedione for PPAR-g, would show efficacy against the cerebral
      infarction and neurological dysfunctions induced by embolic middle cerebral
      artery (MCA) occlusion in the rat. 3. Focal ischaemic injury was induced by
      embolizing a preformed clot into the MCA. Rosiglitazone was dissolved in dimethyl
      sulphoxide and injected i.p. 1 h before MCA occlusion at doses of 0.33, 0.1, 0.3
      or 1 mg/kg. In addition, 1 mg/kg rosiglitazone was used immediately or 4 h after
      embolization. Forty-eight hours after MCA occlusion, brains were removed,
      sectioned and stained with a 2% solution of 2,3,5-triphenyltetrazolum chloride
      and analysed using a commercial image-processing software program. 4. When
      rosiglitazone was administered 1 h before embolization, it significantly reduced
      infarct volume by 48.2, 68.4% and 70.3% at doses of 0.1, 0.3 and 1 mg/kg,
      respectively (P < 0.001). Administration of rosiglitazone (1 mg/kg) immediately
      or 4 h after stroke also reduced infarct volume by 67 and 50.8%, respectively (P
      < 0.001). Rosiglitazone-treated rats also demonstrated improved neurological
      functions. However, there were no statistically significant differences between
      control and treated groups in terms of brain oedema at 48 h after ischaemic
      injury. 5. The findings of the present study may support the idea of a potential
      benefit of thiazolidinediones in the management of ischaemic stroke.

PMID- 17042915
TI  - Altering extracellular potassium concentration does not modulate drug block of
      human ether-a-go-go-related gene (hERG) channels.
AB  - 1. Drug-induced block of the rapidly activating delayed rectifier K+ current
      (I(Kr)), encoded by human ether-a-go-go-related gene (hERG), has been linked to
      acquired long QT syndrome (aLQTS). Hypokalaemia is a recognized risk factor in
      aLQTS. To further understand why hypokalaemia is a risk factor in aLQTS, we
      examined the effect of [K+]o on drug block of the hERG potassium channel stably
      expressed in human embryonic kidney (HEK-293) cells using whole-cell voltage
      clamp techniques. 2. The effects of selected [K+]o (1-20 mmol/L) on hERG block
      with four structurally diverse compounds (dofetilide, mesoridazine, quinidine and
      terfenadine) from different therapeutic classes were evaluated. Reducing [K+]o
      from 20 to 1 mmol/L had little effect on IC50 values for hERG current block for
      all four compounds. For example, evaluating quinidine in external potassium
      concentrations of 20, 10, 5 and 1 mmol/L resulted in IC50 values of 1.82 +/-
      0.33, 2.04 +/- 0.28, 1.57 +/- 0.52 and 1.14 +/- 0.21 mmol/L, respectively. No
      statistically significant difference (P > 0.35, anova) was observed between drug
      block of hERG in different external potassium concentrations. These data are in
      contrast with previously reported results examining hERG channel modulation
      expressed in AT-1 cells under similar experimental conditions. 3. These results
      demonstrate that [K+]o does not directly modulate drug block of hERG channels
      expressed in an HEK-293 cell line. The enhanced risk of Torsades de Pointes
      associated with hypokalaemia in aLQTS may be due to reduction of other (non-hERG)
      potassium currents, further reducing the repolarization reserve, and not due to
      direct modulation of hERG block by [K+]o.

PMID- 17042916
TI  - CPU0507, an endothelin receptor antagonist, improves rat hypoxic pulmonary artery
      hypertension and constriction in vivo and in vitro.
AB  - 1. The Aim Of The Present Study Was To Test The Efficacy Of The Novel Endothelin
      (Et) Receptor Antagonist CPU0507 In Treating Rat Hypoxic Pulmonary Hypertension
      (Ph) In Vivo And In Vitro And To Explore The Role Of The Et-1 System In The
      Disease. 2. Male Sprague-dawley Rats (220 +/- 20 G) Were Divided Into Four
      Groups: (I) Control; (Ii) Untreated Hypoxic (28 Days Hypoxia); (Iii) Hypoxic Rats
      Treated In The Last 5 Days Of Hypoxia With Nifedipine(5 Mg/kg Per Day, P.o.); And
      (Iv) Hypoxic Rats Treated In The Last 5 Days Of Hypoxia With CPU0507 (20 Mg/kg
      Per Day, S.c.). Effects Of Treatments On Haemodynamics And Biochemical Data, As
      Well As Functional Assessments Of The Isolated Pulmonary Artery, Were Determined
      In Vivo And In Vitro. 3. It Was Found That CPU0507 Reduced The Elevated Pulmonary
      Arterial Pressure And Right Heart Weight Index And Restored Abnormalities In
      Nitric Oxide (No), Malondialdehyde And No Synthase (Nos) In The Serum And
      Superoxide Dismutase, Hydroxyproline And Nos In Pulmonary Homogenates. In
      Addition, CPU0507 Restored Altered Pulmonary Vasoconstrictor And Vasodilator
      Responses. Vascular Constriction And Dilatation Of Untreated Pulmonary Arteries
      Were Reverted Effectively Towards Normal Following Exposure Of Artery Rings To
      CPU0507 In Vitro. 4. In Conclusion, The Results Indicate That Hypoxic Ph Is
      Relieved Significantly By CPU0507 In Vivo And In Vitro And The Effects Are
      Presumed To Be Mediated By Suppression Of The Et-reactive Oxygen Species Axis.

PMID- 17042917
TI  - N(G)-nitro-L-arginine methyl ester potentiates anaphylactic venoconstriction in
      rat perfused livers.
AB  - 1. The effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine
      methyl ester (L-NAME) on anaphylaxis-induced venoconstriction were examined in
      rat isolated livers perfused with blood-free solutions in order to clarify the
      role of NO in anaphylactic venoconstriction. 2. Rats were sensitized with
      ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in
      a recirculating manner at a constant flow with Krebs'-Henseleit solution. The
      antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after
      pretreatment with L-NAME (100 micromol/L) or D-NAME (100 micromol/L) and changes
      in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow
      were monitored. In addition, concentrations of the stable metabolites of NO ( and
      ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen
      caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean
      (SEM) baseline value of 7.7 +/- 0.1 cmH2O to a peak of 21.4 +/- 1.1 cmH2O at 3
      min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic
      venoconstriction, as reflected by a higher Ppv (27.4 +/- 0.8 cmH2O) after antigen
      than observed following D-NAME pretreatment. The addition of L-arginine, a
      precursor for the synthesis of NO, reversed the augmentation of anaphylactic
      venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the
      production of NO, which consequently attenuated anaphylactic venoconstriction.
      However, perfusate NOx levels did not increase significantly after antigen in
      livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME
      potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO
      contributes to the attenuation of the venoconstriction. However, this functional
      evidence was not accompanied by corresponding changes in perfusate NOx
      concentrations.

PMID- 17042918
TI  - Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug
      treatment.
AB  - 1. Metabolism of tryptophan along the oxidative pathway via kynurenine results in
      the production of quinolinic acid and kynurenic acid, which can act on glutamate
      receptors in peripheral tissues. We have now measured the concentrations of
      kynurenine pathway metabolites in the plasma of patients with osteoporosis before
      treatment with drugs, throughout and after 2 years of treatment with the drugs
      raloxifene or etidronate. Oxidative stress was assessed by measuring levels of
      the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines
      were analysed by HPLC. Bone density was measured using dual-energy X-ray
      absorptiometry scans. 2. Patients with osteoporosis showed significantly lower
      baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but
      significantly higher levels of anthranilic acid and lipid peroxidation products.
      After 2 years treatment with etidronate and calcium, we observed significant
      therapeutic responses quantified by bone densitometric scanning. Significant
      improvements were not seen in patients treated with raloxifene. 3. In parallel,
      the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation
      products were restored to control values by both drug treatments studied and
      tryptophan levels were increased significantly compared with baseline values. 4.
      The results suggest that tryptophan metabolism is altered in osteoporosis in a
      manner that could contribute to the oxidative stress and, thus, to progress of
      the disease. The oxidative metabolism of tryptophan (the kynurenine pathway)
      could represent a novel target for the development of new drugs for the treatment
      of osteoporosis. In addition, we noted that etidronate is a more effective drug
      than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory
      drugs may reduce the efficacy of etidronate.

PMID- 17042919
TI  - Voltage and ionic regulation of human serotonin transporter in Xenopus oocytes.
AB  - 1. The serotoninergic system is known to be involved in the control of multiple
      behavioural and physiological functions. The serotonin (5-hydroxtryptamine; 5-HT)
      transporter (SERT), which controls the synaptic 5-HT concentration through re
      uptake of this neurotransmitter into presynaptic terminals, has been a primary
      therapeutic target for various psychiatric and peripheral disorders. The aim of
      the present study was to identify the regulatory mechanism(s) of the human SERT
      (hSERT) in heterologously expressed oocytes. 2. The hSERT cRNA was transcribed in
      vitro and injected into Xenopus oocytes. The 5-HT-induced transporter currents
      were measured by voltage clamp. The effects of extracellular sodium or chloride
      were studied by replacement perfusion with tetramethylammonium-chloride (96
      mmol/L) or sodium acetate (96 mmol/L). In addition, to alter the internal calcium
      concentration, CaCl2 (50 micromol/L) and inositol triphosphate (IP3; 50
      micromol/L), with or without EGTA (2.5 mmol/L), were injected into oocytes. The
      specificity of 5-HT-sensitive currents was determined by the use of the SERT
      antagonist desipramine and niflumic acid to block background chloride currents.
      3. The hSERT-expressing oocytes displayed voltage-dependent, 5-HT-induced
      currents that increased at negative potentials. Replacing extracellular sodium or
      chloride significantly decreased the hSERT currents by 89 and 45%, respectively
      (P < 0.05, n = 7 each). Injection of IP3 or CaCl2 increased the hSERT currents by
      approximately 65% (P < 0.05; n = 10 each) and the effect of IP3 was abolished by
      preinjection of EGTA. 4. These results demonstrate that hSERT activity is not
      only voltage dependent, but is also affected by intracellular calcium and
      extracellular sodium and chloride.

PMID- 17042921
TI  - L-glutamate and glutamine improve haemodynamic function and restore myocardial
      glycogen content during postischaemic reperfusion: A radioactive tracer study in
      the rat isolated heart.
AB  - 1. L-Glutamate and glutamine have been suggested to have cardioprotective
      effects. However, the issue is controversial and the metabolic mechanisms
      underlying a beneficial effect are not well understood. 2. In the present study
      we investigated the effects of L-glutamate and glutamine on haemodynamic
      recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake
      during postischaemic reperfusion. 3. Hearts from male Wistar rats (250-300 g)
      were divided into three groups as follows: (i) control (n = 12); (ii) L-glutamate
      (n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff
      preparation and perfused with oxygenated Krebs'-Henseleit solution at 80 mmHg and
      37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which
      L-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left
      ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]
      glucose and myocardial glucose uptake using D-[2-3H]-glucose were measured. 4. L
      Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts
      for both). L-Glutamate and glutamine increased de novo glycogen synthesis by 78%
      (P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total
      myocardial glycogen content was increased by both L-glutamate and glutamine (5.7
      +/- 0.3 and 6.2 +/- 0.7 micromol/g wet weight, respectively; P < 0.05 and 0.01,
      respectively) compared with that in control hearts (3.6 +/- 0.4 micromol/g wet
      weight). Neither L-glutamate nor glutamine affected myocardial glucose uptake
      during reperfusion. 5. Improved postischaemic haemodynamic recovery after L
      glutamate and glutamine supplementation during reperfusion is associated with
      increased de novo glycogen synthesis, suggesting a favourable modulation of
      intracellular myocardial carbohydrate metabolism.

PMID- 17042920
TI  - Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine
      pharmacokinetics after renal transplantation.
AB  - 1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft
      rejection after solid organ transplantation. It has a narrow therapeutic index
      and shows considerable interindividual differences in its pharmacokinetics.
      Interindividual differences in the activity and expression of the metabolising
      enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P
      glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics.
      Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to
      result from genetic polymorphisms encoding their genes. 2. The aim of the present
      study was to evaluate retrospectively the effects of genetic polymorphisms of
      CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration
      during the early period after renal transplantation in Chinese patients. 3. One
      hundred and six renal transplant recipients in China were genotyped by polymerase
      chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3
      and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence
      polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were
      determined and compared among the different genotype groups. 4. The frequency of
      the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95%
      confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528
      (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete
      linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1
      genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per
      mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg
      (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was
      26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal
      Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non
      expressors than expressors in the first week after renal transplantation. In
      addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but
      significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7
      (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014,
      Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic
      polymorphisms in CYP3A5 may be responsible, in part, for the large
      interindividual variability of cyclosporine pharmacokinetics during the early
      phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3
      variant genotype require a low dose of cyclosporine to reach target levels
      compared with those with the CYP3A5*1 allele.

PMID- 17042922
TI  - Antihyperglycaemic and antiperoxidative roles of acarbose in type 2 diabetes
      mellitus are possibly mediated through changes in thyroid function.
AB  - 1. The aim of the present study was to reveal the possible involvement of thyroid
      hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. 2.
      The effects of acarbose on changes in serum concentration of thyroid hormones,
      insulin and glucose in dexamethasone-induced type 2 diabetic mice were
      investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced
      glutathione (GSH) content and the activity of associated endogenous anti-oxidant
      enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were
      investigated in renal and cardiac tissues, which are commonly affected in
      diabetes mellitus. 3. Although administration of dexamethasone (1.0 mg/kg, i.m.,
      for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and
      tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD
      and CAT. 4. When dexamethasone-induced hyperglycaemic mice were treated with
      acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were
      increased and most of the abnormalities, including serum insulin and glucose
      levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. 5. These
      findings suggest the involvement of thyroid hormones in the mode of action of
      acarbose in amelioration of type 2 diabetes mellitus.

PMID- 17042923
TI  - Regulation of ryanodine receptors from skeletal and cardiac muscle during rest
      and excitation.
AB  - 1. In muscle, intracellular calcium concentration, hence skeletal muscle force
      and cardiac output, is regulated by uptake and release of calcium from the
      sarcoplasmic reticulum (SR). The ryanodine receptor (RyR) forms the calcium
      release channel in the SR. 2. Calcium release through RyRs is modulated by a wide
      variety of endogenous molecules, including small diffusible ligands such as ATP,
      Ca2+ and Mg2+. The regulation of RyR channels by ATP, Ca2+ and Mg2+ is a complex
      interplay of several regulatory mechanisms, which are still being unravelled.
      Consequently, it is not clearly known how RyRs are regulated in resting muscle
      and during contraction. 3. The present paper reviews factors controlling the
      activity of RyRs in skeletal and cardiac muscle with an emphasis on mechanistic
      insights derived from single channel recording methods. 4. In addition, the
      nature of dihydropyridine receptor (DHPR) control of RyRs in skeletal muscle
      derived from experiments with peptide fragments of the DHPR II-III loop is
      reviewed. 5. Finally, recent experiments on coupled RyRs in lipid bilayers and
      their potential for resolving the elusive mechanisms controlling calcium release
      during cardiac contraction are discussed.

PMID- 17042924
TI  - Structural and functional characterization of interactions between the
      dihydropyridine receptor II-III loop and the ryanodine receptor.
AB  - 1. Excitation-contraction coupling in skeletal muscle is dependent on a physical
      interaction between the dihydropyridine receptor (DHPR) and the ryanodine
      receptor (RyR). 2. A number of peptides derived from the II-III loop region of
      the DHPR have been shown to be functionally active in stimulating the release of
      calcium via RyR channels. Their function has been found to correlate with the
      presence of a basic helical region located at the N-terminus of the II-III loop.
      3. The entire recombinant skeletal DHPR II-III loop is an efficient activator of
      RyR1 and RyR2. 4. The skeletal DHPR II-III loop is comprised of a series of a
      helices, but its tertiary structure has been determined to be unstructured and
      flexible. 5. Fluorescence quenching experiments have been used to identify and
      measure the binding affinity of the II-III loop with fragments of the RyR.

PMID- 17042925
TI  - ClC-1 chloride channel: Matching its properties to a role in skeletal muscle.
AB  - 1. ClC-1 is a Cl- channel in mammalian skeletal muscle that plays an important
      role in membrane repolarization following muscular contraction. Reduction of ClC
      1 conductance results in myotonia, a state characterized by muscle
      hyperexcitability. 2. As is the case for other members of the ClC family, ClC-1
      exists as a dimer that forms a double-barrelled channel. Each barrel, or pore, of
      ClC-1 is gated by its own gate ('fast' or 'single pore' gate), whereas both pores
      are gated simultaneously by another mechanism ('slow' or 'common' gate). 3.
      Comparison of the biophysical and pharmacological properties of heterologously
      expressed ClC-1 with the properties of the Cl- conductance measured in skeletal
      muscle strongly suggests that ClC-1 is the major Cl- channel responsible for
      muscle repolarization. However, not all results obtained in experiments on whole
      muscle or muscle fibres support this notion. 4. In the present review we attempt
      to bring together the current knowledge of ClC-1 with the physiology of skeletal
      muscle.

PMID- 17042926
TI  - Immune deficiencies and parasitic diseases.

PMID- 17042928
TI  - Primary immunodeficiencies and susceptibility to parasitic infections.
AB  - Primary immunodeficiencies are important disorders because they typically cause
      severe illness in affected patients. In addition, these diseases provide a unique
      glimpse at the underpinnings of the immune system in humans. Susceptibility to
      infections, including those caused by parasites, is a hallmark of these immune
      defects. Understanding the association between primary immunodeficiencies and
      parasitic infections will likely improve our grasp on the mechanisms of defense
      against these pathogens.

PMID- 17042930
TI  - Co-infection of malaria with HIV: an immunological perspective.
AB  - Human immunodeficiency virus (HIV) and Plasmodium parasites are pathogens that
      induce significant perturbation and activation of the immune system. Due to their
      geographical overlap, there have been concerns that co-infection with the two
      pathogens may be a factor in the modification of their development, and in the
      severity and rate of disease progression that they induce. In this article, we
      have reviewed some of the studies that have addressed this topic and we have
      tried to provide immunological mechanisms to explain these potential
      interactions.

PMID- 17042929
TI  - Interactions of malnutrition and immune impairment, with specific reference to
      immunity against parasites.
AB  - 1. Clinical malnutrition is a heterogenous group of disorders including
      macronutrient deficiencies leading to body cell mass depletion and micronutrient
      deficiencies, and these often coexist with infectious and inflammatory processes
      and environmental problems. 2. There is good evidence that specific
      micronutrients influence immunity, particularly zinc and vitamin A. Iron may have
      both beneficial and deleterious effects depending on circumstances. 3. There is
      surprisingly slender good evidence that immunity to parasites is dependent on
      macronutrient intake or body composition.

PMID- 17042931
TI  - Interactions between schistosomiasis and infection with HIV-1.
AB  - In many regions of the world, both schistosomiasis and HIV/AIDS are endemic,
      resulting in patients harbouring co-infections. Because interaction with host
      CD4(+) T cells is a characteristic of schistosome as well as HIV-1 infections, bi
      directional disease effects may be sufficiently different from sequelae caused by
      either infectious agent alone to warrant alteration of public health approaches
      in areas of co-endemnicity. Studies published over the past decade provide useful
      insights into interactions between schistosomiasis and infection with HIV-1, and
      overall support the hypothesis that special emphasis on treatment of
      schistosomiasis in populations with elevated prevalence or risk of HIV-1
      infection is justified.

PMID- 17042927
TI  - The immunology of parasite infections in immunocompromised hosts.
AB  - Immune compromise can modify the severity and manifestation of some parasitic
      infections. More widespread use of newer immnosuppressive therapies, the growing
      population of individuals with immunocompromised states as well as the prolonged
      survival of these patients have altered the pattern of parasitic infection. This
      review article discusses the burden and immunology of parasitic infections in
      patients who are immunocompromised secondary to congenital immunodeficiency,
      malnutrition, malignancy, and immunosuppressive medications. This review does not
      address the literature on parasitic infections in the setting of HIV-1 infection.

PMID- 17042932
TI  - HIV and helminth co-infection: is deworming necessary?
AB  - We have previously suggested that helminth infections play a major role in the
      pathogenesis of HIV-1 infection in Africa and other developing areas, due to
      their profound effects on the host immune system, which make those infected more
      susceptible to HIV-1 infection and less able to cope with it. Chronic immune
      activation with a dominant Th2 profile, and anergy, are the hallmarks of chronic
      helminth infection, and may therefore account for most of these effects. In the
      present review, we summarize the studies that have addressed these issues and
      argue that despite some conflicting results, the cumulative immunological and
      epidemiological evidence is in favour of deworming as a preventive and possible
      therapeutic measure vis-a-vis HIV-1 infection. We suggest that it should be at
      least tested on a wider and larger scale than has been done until now, because of
      its immense potential impact on the still raging AIDS epidemic in developing
      countries.

PMID- 17042933
TI  - Helminths and HIV infection: epidemiological observations on immunological
      hypotheses.
AB  - Parasitic helminths have co-evolved with the mammalian immune system. Current
      hypotheses suggest that immunological stimulation in the presence of helminths is
      balanced by immuno-regulation and by the broad spectrum of mechanisms possessed
      by helminths for countering the host immune response. The degree to which this
      balance is perfected, and the mechanisms by which this is achieved, vary between
      helminth species; we suggest that this is reflected not only in the degree of
      pathology induced by helminths but also in a variety of relationships with HIV
      infection and HIV disease. Available epidemiological data regarding interactions
      between helminths and HIV are largely observational; results are variable and
      generally inconclusive. Well designed, controlled intervention studies are
      required to provide definitive information on the species-specific nature of
      these interactions and on the advantages, disadvantages and optimal timing of de
      worming in relation to HIV infection.

PMID- 17042935
TI  - REEF: searching REgionally Enriched Features in genomes.
AB  - BACKGROUND: In Eukaryotic genomes, different features including genes are not
      uniformly distributed. The integration of annotation information and genomic
      position of functional DNA elements in the Eukaryotic genomes opened the way to
      test novel hypotheses of higher order genome organization and regulation of
      expression. RESULTS: REEF is a new tool, aimed at identifying genomic regions
      enriched in specific features, such as a class or group of genes homogeneous for
      expression and/or functional characteristics. The method for the calculation of
      local feature enrichment uses test statistic based on the Hypergeometric
      Distribution applied genome-wide by using a sliding window approach and adopting
      the False Discovery Rate for controlling multiplicity. REEF software, source code
      and documentation are freely available at
      http://telethon.bio.unipd.it/bioinfo/reef/. CONCLUSION: REEF can aid to shed
      light on the role of organization of specific genomic regions in the
      determination of their functional role.

PMID- 17042936
TI  - Comparison of capillary based microflurometric assay for CD4+ T cell count
      estimation with dual platform Flow cytometry.
AB  - The CD4+ T cell count estimation is an important monitoring tool for HIV disease
      progression and efficacy of anti-retroviral treatment (ART). Due to availability
      of ART at low cost in developing countries, quest for reliable cost effective
      alternative methods for CD4+ T cell count estimation has gained importance. A
      simple capillary-based microflurometric assay (EasyCD4 System, Guava Technology)
      was compared with the conventional flow cytometric assay for estimation of CD4+ T
      cell counts in 79 HIV infected individuals. CD4+ T cell count estimation by both
      the assays showed strong correlation (r = 0.938, p < 0.001, 95% CI 0.90 to 0.96).
      The Bland Altman plot analysis showed that the limits of variation were within
      agreeable limits of +/- 2SD (-161 to 129 cells/mm3). The Easy CD4 assay showed
      100% sensitivity for estimating the CD4+ T cell counts < 200 cells/mm3 and < 350
      cells/mm3 and 97% sensitivity to estimate CD4+ T cell count < 500 cells/mm3. The
      specificity ranged from 82 to 100%. The Kappa factor ranged from 0.735 for the
      CD4+ T cell counts < 350 cells/mm3 to 0.771 for < 500 cells/mm3 CD4+ T cell
      counts. The system works with a simple protocol, is easy to maintain and has low
      running cost. The system is compact and generates minimum amount of waste. Hence
      the EasyCD4 System could be applied for estimation of CD4+ T cell counts in
      resource poor settings.

PMID- 17042934
TI  - Immune reconstitution disease associated with parasitic infections following
      antiretroviral treatment.
AB  - HIV-associated immune reconstitution disease (IRD) is the clinical presentation
      or deterioration of opportunistic infections that results from enhancement of
      pathogen-specific immune responses among patients responding to antiretroviral
      treatment (ART). The vast majority of reported cases of IRD have been associated
      with mycobacterial, chronic viral and invasive fungal infections; such cases
      result from dysregulated augmentation of cell-mediated type 1 cytokine-secreting
      host immune responses. However, the spectrum of infections now recognized as
      associated with IRD is expanding and includes a number of parasitic infections,
      which may be mediated by different immunopathological mechanisms. These include
      leishmaniasis (visceral, cutaneous, mucosal and post kala azar dermal
      leishmaniasis), schistosomiasis and strongyloidiasis. Since the major burden of
      HIV lies in resource-limited countries where access to ART is now rapidly
      expanding, increased awareness and knowledge of these phenomena is important.
      Here we review the clinical spectrum and pathogenesis of IRD associated with
      parasitic infections.

PMID- 17042937
TI  - Atlanto-axial rotatory fixation in a girl with Spondylocarpotarsal synostosis
      syndrome.
AB  - We report a 15-year-old girl who presented with spinal malsegmentation,
      associated with other skeletal anomalies. The spinal malsegmentation was
      subsequently discovered to be part of the spondylocarpotarsal synostosis
      syndrome. In addition, a distinctive craniocervical malformation was identified,
      which included atlanto-axial rotatory fixation. The clinical and the radiographic
      findings are described, and we emphasise the importance of computerised
      tomography to characterize the craniocervical malformation complex. To the best
      of our knowledge, this is the first clinical report of a child with
      spondylocarpotarsal synostosis associated with atlanto-axial rotatory fixation.

PMID- 17042938
TI  - Alternative technologies in cervical cancer screening: a randomised evaluation
      trial.
AB  - BACKGROUND: Cervical cancer screening programmes have markedly reduced the
      incidence and mortality rates of the disease. A substantial amount of deaths from
      the disease could be prevented further by organised screening programmes or
      improving currently running programmes. METHODS/DESIGN: We present here a
      randomised evaluation trial design integrated to the Finnish cervical cancer
      screening programme, in order to evaluate renewal of the programme using emerging
      technological alternatives. The main aim of the evaluation is to assess screening
      effectiveness, using subsequent cancers as the outcome and screen-detected pre
      cancers as surrogates. For the time being, approximately 863,000 women have been
      allocated to automation-assisted cytology, human papillomavirus (HPV) DNA
      testing, or to conventional cytology within the organised screening programme.
      Follow-up results on subsequent cervical cancers will become available during
      2007-2015. DISCUSSION: Large-scale randomised trials are useful to clarify
      effectiveness and cost-effectiveness issues of the most important technological
      alternatives in the screening programmes for cervical cancer.

PMID- 17042939
TI  - Time- and concentration-dependent changes in gene expression induced by
      benzo(a)pyrene in two human cell lines, MCF-7 and HepG2.
AB  - BACKGROUND: The multi-step process of carcinogenesis can be more fully understood
      by characterizing gene expression changes induced in cells by carcinogens. In
      this study, expression microarrays were used to monitor the activity of 18,224
      cDNA clones in MCF-7 and HepG2 cells exposed to the carcinogen benzo(a)pyrene
      (BaP) or its non-carcinogenic isomer benzo(e)pyrene (BeP). Time and concentration
      gene expression effects of BaP exposure have been assessed and linked to other
      measures of cellular stress to aid in the identification of novel genes/pathways
      involved in the cellular response to genotoxic carcinogens. RESULTS: BaP (0.25
      5.0 muM; 6-48 h exposure) modulated 202 clones in MCF-7 cells and 127 in HepG2
      cells, including 27 that were altered in both. In contrast, BeP did not induce
      consistent gene expression changes at the same concentrations. Significant time-
      and concentration-dependent responses to BaP were seen in both cell lines.
      Expression changes observed in both cell lines included genes involved in
      xenobiotic metabolism (e.g., CYP1B1, NQO1, MGST1, AKR1C1, AKR1C3,CPM), cell cycle
      regulation (e.g., CDKN1A), apoptosis/anti-apoptosis (e.g., BAX, IER3), chromatin
      assembly (e.g., histone genes), and oxidative stress response (e.g., TXNRD1).
      RTqPCR was used to validate microarray data. Phenotypic anchoring of the
      expression data to DNA adduct levels detected by 32P-postlabelling, cell cycle
      data and p53 protein expression identified a number of genes that are linked to
      these biological outcomes, thereby strengthening the identification of target
      genes. The overall response to BaP consisted of up-regulation of tumour
      suppressor genes and down-regulation of oncogenes promoting cell cycle arrest and
      apoptosis. Anti-apoptotic signalling that may increase cell survival and promote
      tumourigenesis was also evident. CONCLUSION: This study has further characterised
      the gene expression response of human cells after genotoxic insult, induced after
      exposure to concentrations of BaP that result in minimal cytotoxicity. We have
      demonstrated that investigating the time and concentration effect of a carcinogen
      on gene expression related to other biological end-points gives greater insight
      into cellular responses to such compounds and strengthens the identification of
      target genes.

PMID- 17042940
TI  - Severe malnutrition with and without HIV-1 infection in hospitalised children in
      Kampala, Uganda: differences in clinical features, haematological findings and
      CD4+ cell counts.
AB  - BACKGROUND: The aim of this study was to describe the clinical features,
      haematological findings and CD4+ and CD8+ cell counts of severely malnourished
      children in relation to human immunodeficiency virus (HIV) infection. METHODS:
      The study was conducted in the paediatric wards of Mulago hospital, which is
      Uganda's national referral and teaching hospital. We studied 315 severely
      malnourished children (presence of oedema and/or weight-for-height: z-score < -3)
      and have presented our findings. At admission, the CD4+ and CD8+ cells were
      measured by the flow cytometry and HIV serology was confirmed by Enzyme linked
      Immunoassay for children >18 months of age, and RNA PCR was performed for those <
      or =18 months. Complete blood count, including differential counts, was
      determined using a Beckman Coulter counter. RESULTS: Among the 315 children, 119
      (38%) were female; the median age of these children was 17 months (Interquartile
      range 12-24 months), and no difference was observed in the HIV status with regard
      to gender or age. The children showed a high prevalence of infections: pneumonia
      (68%), diarrhoea (38%), urinary tract infection (26%) and bacteraemia (18%), with
      no significant difference with regard to the HIV status (HIV-positive versus HIV
      negative children). However, the HIV-positive children were more likely to have
      persistent diarrhoea than the HIV-uninfected severely malnourished children (odds
      ratio (OR) 2.0, 95% confidence interval (CI) 1.2-3.6). When compared with the HIV
      negative children, the HIV-positive children showed a significantly lower median
      white blood cell count (10700 versus 8700) and lymphocyte count (4033 versus
      2687). The CD4+ cell percentages were more likely to be lower in children with
      non-oedematous malnutrition than in those with oedematous malnutrition even after
      controlling for the HIV infection. The novel observation of this study is that
      the CD4+ percentages in both HIV-positive and HIV-negative children without
      oedema were lower that those in children with oedema. These observations appear
      to imply that the development of oedema requires a certain degree of
      immunocompetence, which is an interesting clue to the pathophysiology of oedema
      in severe malnutrition.

PMID- 17042942
TI  - Whole genome association mapping by incompatibilities and local perfect
      phylogenies.
AB  - BACKGROUND: With current technology, vast amounts of data can be cheaply and
      efficiently produced in association studies, and to prevent data analysis to
      become the bottleneck of studies, fast and efficient analysis methods that scale
      to such data set sizes must be developed. RESULTS: We present a fast method for
      accurate localisation of disease causing variants in high density case-control
      association mapping experiments with large numbers of cases and controls. The
      method searches for significant clustering of case chromosomes in the "perfect"
      phylogenetic tree defined by the largest region around each marker that is
      compatible with a single phylogenetic tree. This perfect phylogenetic tree is
      treated as a decision tree for determining disease status, and scored by its
      accuracy as a decision tree. The rationale for this is that the perfect phylogeny
      near a disease affecting mutation should provide more information about the
      affected/unaffected classification than random trees. If regions of compatibility
      contain few markers, due to e.g. large marker spacing, the algorithm can allow
      the inclusion of incompatibility markers in order to enlarge the regions prior to
      estimating their phylogeny. Haplotype data and phased genotype data can be
      analysed. The power and efficiency of the method is investigated on 1) simulated
      genotype data under different models of disease determination 2) artificial data
      sets created from the HapMap ressource, and 3) data sets used for testing of
      other methods in order to compare with these. Our method has the same accuracy as
      single marker association (SMA) in the simplest case of a single disease causing
      mutation and a constant recombination rate. However, when it comes to more
      complex scenarios of mutation heterogeneity and more complex haplotype structure
      such as found in the HapMap data our method outperforms SMA as well as other
      fast, data mining approaches such as HapMiner and Haplotype Pattern Mining (HPM)
      despite being significantly faster. For unphased genotype data, an initial step
      of estimating the phase only slightly decreases the power of the method. The
      method was also found to accurately localise the known susceptibility variants in
      an empirical data set--the DeltaF508 mutation for cystic fibrosis--where the
      susceptibility variant is already known--and to find significant signals for
      association between the CYP2D6 gene and poor drug metabolism, although for this
      dataset the highest association score is about 60 kb from the CYP2D6 gene.
      CONCLUSION: Our method has been implemented in the Blossoc (BLOck aSSOCiation)
      software. Using Blossoc, genome wide chip-based surveys of 3 million SNPs in 1000
      cases and 1000 controls can be analysed in less than two CPU hours.

PMID- 17042941
TI  - Stroke prevalence among the Spanish elderly: an analysis based on screening
      surveys.
AB  - BACKGROUND: This study sought to describe stroke prevalence in Spanish elderly
      populations and compare it against that of other European countries. METHODS: We
      identified screening surveys--both published and unpublished--in Spanish
      populations, which fulfilled specific quality requirements and targeted
      prevalence of stroke in populations aged 70 years and over. Surveys covering
      seven geographically different populations with prevalence years in the period
      1991-2002 were selected, and the respective authors were then asked to provide
      descriptions of the methodology and raw age-specific data by completing a
      questionnaire. In addition, five reported screening surveys in European
      populations furnished useful data for comparison purposes. Prevalence data were
      combined, using direct adjustment and logistic regression. RESULTS: The overall
      study population, resident in central and north-eastern Spain, totalled 10,647
      persons and yielded 715 cases. Age-adjusted prevalences, using the European
      standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes.
      Prevalence was significantly lower in women, OR 0.79 95% CI 0.68-0.93, increased
      with age, particularly among women, and displayed a threefold spatial variation
      with statistically significant differences. Prevalences were highest, 8.7%, in
      suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish
      populations, statistically significant differences were seen in eight Italian
      populations, OR 1.39 95% CI (1.18-1.64), and in Kungsholmen, Sweden, OR 0.40 95%
      CI (0.27-0.58). CONCLUSION: Prevalence in central and north-eastern Spain is
      higher in males and in suburban areas, and displays a threefold geographic
      variation, with women constituting the majority of elderly stroke sufferers.
      Compared to reported European data, stroke prevalence in Spain can be said to be
      medium and presents similar age- and sex-specific traits.

PMID- 17042943
TI  - Building multiclass classifiers for remote homology detection and fold
      recognition.
AB  - BACKGROUND: Protein remote homology detection and fold recognition are central
      problems in computational biology. Supervised learning algorithms based on
      support vector machines are currently one of the most effective methods for
      solving these problems. These methods are primarily used to solve binary
      classification problems and they have not been extensively used to solve the more
      general multiclass remote homology prediction and fold recognition problems.
      RESULTS: We present a comprehensive evaluation of a number of methods for
      building SVM-based multiclass classification schemes in the context of the SCOP
      protein classification. These methods include schemes that directly build an SVM
      based multiclass model, schemes that employ a second-level learning approach to
      combine the predictions generated by a set of binary SVM-based classifiers, and
      schemes that build and combine binary classifiers for various levels of the SCOP
      hierarchy beyond those defining the target classes. CONCLUSION: Analyzing the
      performance achieved by the different approaches on four different datasets we
      show that most of the proposed multiclass SVM-based classification approaches are
      quite effective in solving the remote homology prediction and fold recognition
      problems and that the schemes that use predictions from binary models constructed
      for ancestral categories within the SCOP hierarchy tend to not only lead to lower
      error rates but also reduce the number of errors in which a superfamily is
      assigned to an entirely different fold and a fold is predicted as being from a
      different SCOP class. Our results also show that the limited size of the training
      data makes it hard to learn complex second-level models, and that models of
      moderate complexity lead to consistently better results.

PMID- 17042945
TI  - C-reactive protein in aortic valve disease.
AB  - Aortic Valve Disease, includes a range of disorder severity from mild leaflet
      thickening without valve obstruction, "aortic sclerosis", to severe calcified
      aortic stenosis. It is a slowly progressive active process of valve modification
      similar atherosclerosis for cardiovascular risk factors, lipoprotein deposition,
      chronic inflammation, and calcification. Systemic signs of inflammation, as wall
      and serum CRP, similar to those found in atherosclerosis, are present in patients
      with degenerative aortic valve stenosis and may be expression of a common
      disease, useful in monitoring of stenosis progression.

PMID- 17042944
TI  - The eggshell is required for meiotic fidelity, polar-body extrusion and
      polarization of the C. elegans embryo.
AB  - BACKGROUND: Fertilization restores the diploid state and begins the process by
      which the single-cell oocyte is converted into a polarized, multicellular
      organism. In the nematode, Caenorhabditis elegans, two of the earliest events
      following fertilization are secretion of the chitinous eggshell and completion of
      meiosis, and in this report we demonstrate that the eggshell is essential for
      multiple developmental events at the one-cell stage. RESULTS: We show that the
      GLD (Germline differentiation abnormal)-1-regulated hexosamine pathway enzyme,
      glucosamine-6-phosphate N-acetyltransferase (GNA)-2, is required for synthesis of
      uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), the substrate for eggshell
      chitin synthesis by chitin synthase-1 (CHS-1). Furthermore, while chs-1(RNAi) or
      combined RNAi with the chitin-binding proteins, CEJ-1 and B0280.5, does not
      interfere with normal meiotic timing, lagging chromosomes are observed at
      meiosis, and polar-body extrusion fails. We also demonstrate that chitin, and
      either CEJ-1 or B0280.5, are essential for the osmotic/permeability barrier and
      for movement of the sperm pronucleus/centrosome complex to the cortex, which is
      associated with the initiation of polarization. CONCLUSION: Our results indicate
      that the eggshell is required in single-cell C. elegans development, playing an
      essential role in multiple actin-dependent early events. Furthermore, the
      earliest meiotic roles precede osmotic barrier formation, indicating that the
      role of the eggshell is not limited to generation of the osmotic barrier.

PMID- 17042946
TI  - Levels of acute phase proteins remain stable after ischemic stroke.
AB  - BACKGROUND: Inflammation and inflammatory biomarkers play an important role in
      atherosclerosis and cardiovascular disease. Little information is available,
      however, on time course of serum markers of inflammation after stroke. METHODS:
      First ischemic stroke patients > or =40 years old had levels of high-sensitivity
      C-reactive protein (hsCRP), serum amyloid A (SAA), and fibrinogen measured in
      plasma samples drawn at 1, 2, 3, 7, 14, 21 and 28 days after stroke. Levels were
      log-transformed as needed, and parametric and non-parametric statistical tests
      were used to test for evidence of a trend in levels over time. Levels of hsCRP
      and SAA were also compared with levels in a comparable population of stroke-free
      participants. RESULTS: Mean age of participants with repeated measures (n = 21)
      was 65.6 +/- 11.6 years, and 13 (61.9%) were men, and 15 (71.4%) were Hispanic.
      Approximately 75% of patients (n = 15) had mild strokes (NIH Stroke Scale score 0
      5). There was no evidence of a time trend in levels of hsCRP, SAA, or fibrinogen
      for any of the markers during the 28 days of follow-up. Mean log(hsCRP) was 1.67
      +/- 1.07 mg/L (median hsCRP 6.48 mg/L) among stroke participants and 1.00 +/-
      1.18 mg/L (median 2.82 mg/L) in a group of 1176 randomly selected stroke-free
      participants from the same community (p = 0.0252). CONCLUSION: Levels of hsCRP
      are higher in stroke patients than in stroke-free subjects. Levels of
      inflammatory biomarkers associated with atherosclerosis, including hsCRP, appear
      to be stable for at least 28 days after first ischemic stroke.

PMID- 17042947
TI  - Cloning, expression and functional activity of deoxyhypusine synthase from
      Plasmodium vivax.
AB  - BACKGROUND: Plasmodium vivax is the most widespread human malaria parasite.
      However, genetic information about its pathogenesis is limited at present, due to
      the lack of a reproducible in vitro cultivation method. Sequencing of the
      Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine
      synthase (DHS) from P. falciparum, the key regulatory enzyme in the first
      committed step of hypusine biosynthesis. DHS is involved in cell proliferation,
      and thus a valuable drug target for the human malaria parasite P. falciparum. A
      comparison of the enzymatic properties of the DHS enzymes between the benign and
      severe Plasmodium species should contribute to our understanding of the
      differences in pathogenicity and phylogeny of both malaria parasites. RESULTS: We
      describe the cloning of a 1368 bp putative deoxyhypusine synthase gene (dhs)
      sequence from genomic DNA of P. vivax PEST strain Salvador I (Accession number
      AJ549098) after touchdown PCR. The corresponding protein was expressed and
      functionally characterized as deoxyhypusine synthase by determination of its
      specific activity and cross-reactivity to human DHS on a Western blot. The
      putative DHS protein from P. vivax displays a FASTA score of 75 relative to DHS
      from rodent malaria parasite, P. yoelii, and 74 relative to that from the human
      parasite, P. falciparum strain 3D7. The ORF encoding 456 amino acids was
      expressed under control of IPTG-inducible T7 promoter, and expressed as a protein
      of approximately 50 kDa (theoretically 52.7 kDa) in E. coli BL21 DE3 cells. The N
      terminal histidine-tagged protein was purified by Nickel-chelate affinity
      chromatography under denaturing conditions. DHS with a theoretical pI of 6.0 was
      present in both eluate fractions. The specific enzymatic activity of DHS was
      determined as 1268 U/mg protein. The inhibitor, N-guanyl-1, 7-diaminoheptane
      (GC7), suppressed specific activity by 36-fold. Western blot analysis performed
      with a polyclonal anti-human DHS antibody revealed cross-reactivity to DHS from
      P. vivax, despite an amino acid identity of 44% between the proteins. CONCLUSION:
      We identify a novel DHS protein in the more benign malaria parasite,P. vivax, on
      the basis of specific enzymatic activity, cross-reactivity with a polyclonal
      antibody against human DHS, and amino acid identity with DHS homologs from the
      rodent malaria parasite, P. yoelii, and human P. falciparum strains.

PMID- 17042948
TI  - Evaluation of three 3ABC ELISAs for foot-and-mouth disease non-structural
      antibodies using latent class analysis.
AB  - BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease of
      even-toed ungulates. Serological diagnosis/surveillance of FMD presents several
      problems as there are seven serotypes worldwide and in the event of vaccination
      it may be necessary to be able to identify FMD infected/exposed animals
      irrespective of their vaccination status. The recent development of non
      structural 3ABC protein (NSP) ELISA tests has greatly advanced sero
      diagnosis/surveillance as these tests detect exposure to live virus for any of
      the seven serotypes of FMD, even in vaccinated populations. This paper analyses
      the performance of three NSP tests using a Bayesian formulation of the Hui-Walter
      latent class model to estimate test sensitivity and specificity in the absence of
      a "gold-standard" test, using sera from a well described cattle population in
      Cameroon with endemic FMD. RESULTS: The analysis found a high sensitivity and
      specificity for both the Danish C-ELISA and the World Organisation for Animal
      Health (O.I.E.) recommended South American I-ELISA. However, the commercial
      CHEKIT kit, though having high specificity, has very low sensitivity. The results
      of the study suggests that for NSP ELISAs, latent class models are a useful
      alternative to the traditional approach of evaluating diagnostic tests against a
      known "gold-standard" test as imperfections in the "gold-standard" may give
      biased test characteristics. CONCLUSION: This study demonstrates that when
      applied to naturally infected zebu cattle managed under extensive rangeland
      conditions, the FMD ELISAs may not give the same parameter estimates as those
      generated from experimental studies. The Bayesian approach allows for full
      posterior probabilities and capture of the uncertainty in the estimates. The
      implications of an imperfect specificity are important for the design and
      interpretation of sero-surveillance data and may result in excessive numbers of
      false positives in low prevalence situations unless a follow-up confirmatory test
      such as the enzyme linked immunoelectrotransfer blot (EITB) is used.

PMID- 17042949
TI  - Re-interpreting conventional interval estimates taking into account bias and
      extra-variation.
AB  - BACKGROUND: The study design with the smallest bias for causal inference is a
      perfect randomized clinical trial. Since this design is often not feasible in
      epidemiologic studies, an important challenge is to model bias properly and take
      random and systematic variation properly into account. A value for a target
      parameter might be said to be "incompatible" with the data (under the model used)
      if the parameter's confidence interval excludes it. However, this
      "incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We
      propose the following way of re-interpreting conventional results. Given a
      specified focal value for a target parameter (typically the null value, but
      possibly a non-null value like that representing a twofold risk), the difference
      between the focal value and the nearest boundary of the confidence interval for
      the parameter is calculated. This represents the maximum correction of the
      interval boundary, for bias and extra-variation, that would still leave the focal
      value outside the interval, so that the focal value remained "incompatible" with
      the data. We describe a short example application concerning a meta analysis of
      air versus pure oxygen resuscitation treatment in newborn infants. Some general
      guidelines are provided for how to assess the probability that the appropriate
      correction for a particular study would be greater than this maximum (e.g. using
      knowledge of the general effects of bias and extra-variation from published bias
      adjusted results). SUMMARY: Although this approach does not yet provide a method,
      because the latter probability can not be objectively assessed, this paper aims
      to stimulate the re-interpretation of conventional confidence intervals, and more
      and better studies of the effects of different biases.

PMID- 17042950
TI  - Anemia, costs and mortality in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Little is known about cost implications of anemia and its association
      with mortality in chronic obstructive pulmonary disease (COPD). This claims
      analysis addresses these questions. METHODS: Using the the US Medicare claims
      database (1997-2001), this study identified Medicare enrollees with an ICD-9
      diagnosis of COPD. Concomitant anemia was identified based on ICD-9 codes or
      receipt of transfusions. Persons with anemia secondary to another disease state,
      a nutritional deficiency or a hereditary disease were excluded. Medicare claims
      and payments, resource utilization and mortality were compared between COPD
      patients with and without anemia. RESULTS: Of the 132,424 enrollees with a COPD
      diagnosis, 21% (n = 27,932) had concomitant anemia. At baseline, anemic patients
      were older, had more co-morbidities and higher rates of health care resource use
      than non-anemic individuals with COPD. In a univariate analysis annual Medicare
      payments for persons with anemia were more than double for those without anemia
      ($1,466 vs. $649, p < 0.001), the direction maintained in all categories of
      payments. Adjusting for demographics, co-morbidities, and other markers of
      disease severity revealed that anemia was independently associated with $3,582
      incremental increase per patient (95% CI: $3,299 to $3,865) in Medicare annual
      reimbursements. The mortality rate among COPD patients with anemia was 262 vs.
      133 deaths per 1,000 person-years among those without anemia (p < 0.001).
      CONCLUSION: Anemia was present in 21% of COPD patients. Although more prevalent
      in more severely ill COPD patients, anemia significantly and independently
      contributes to the costs of care for COPD and is associated with increased
      mortality.

PMID- 17042951
TI  - Audit of the change in the on-call practices in neuroradiology and factors
      affecting it.
AB  - BACKGROUND: On call practices had recently changed at the Newcastle General
      Hospital to accommodate increasing CT scan requests and reduce the workloads of
      the radiologists. In the new system, the person responsible for dealing with the
      out of hours requests for imaging changed from the neuroradiologist to the
      neuroradiographer. This audit was conducted to assess any change in the
      departmental workload as a result of this change. METHODS: The audit was carried
      out over a period of six months and data was collected from the on-call booklets
      which the neuroradiographers maintained and the log books maintained in the
      department of neuroradiology. Details of the imaging requested; the source of the
      request, the reason for the request and the results of the scans were recorded
      and analysed using Microsoft Excel. RESULTS: The number of CT scans requested
      from the A&E went up by 73.4% after the change in practice and majority of these
      increases were due to increased requests for scans on head injuries which
      increased by 122%. Although this was not statistically significant due to lack of
      study power, it is clinically relevant. CONCLUSION: The increase in the number of
      CT scans for head injuries reflects a general change in practice in management of
      head injuries in the UK. Changing the gatekeeper from radiologist to radiographer
      was associated with an increase in CT rate, particularly for head injuries. Other
      factors such as clinician seniority and a greater awareness of the NICE
      guidelines may have also contributed.

PMID- 17042952
TI  - Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem
      cells carrying allelic fluorescent protein genes.
AB  - BACKGROUND: Loss of heterozygosity (LOH) contributes to many cancers, but the
      rate at which these events occur in normal cells of the body is not clear. LOH
      would be detectable in diverse cell types in the body if this event were to
      confer an obvious cellular phenotype. Mice that carry two different fluorescent
      protein genes as alleles of a locus would seem to be a useful tool for addressing
      this issue because LOH would change a cell's phenotype from dichromatic to
      monochromatic. In addition, LOH caused by mitotic crossing over might be
      discernable in tissues because this event produces a pair of neighboring
      monochromatic cells that are different colors. RESULTS: As a step in assessing
      the utility of this approach, we derived primary embryonic fibroblast populations
      and embryonic stem cell lines from mice that carried two different fluorescent
      protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence
      activated cell sorting (FACS) showed that the vast majority of cells in each line
      expressed the two marker proteins at similar levels, and that populations
      exhibited expression noise similar to that seen in bacteria and yeast. Cells with
      a monochromatic phenotype were present at frequencies on the order of 10(-4) and
      appeared to be produced at a rate of approximately 10(-5) variant cells per
      mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the
      expected allele at the ROSA26 locus. More than half of these clones retained
      heterozygosity at a locus between ROSA26 and the centromere. Other clones
      exhibited LOH near the centromere, but were disomic for chromosome 6. CONCLUSION:
      Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by
      FACS. LOH at this locus was usually not accompanied by LOH near the centromere,
      suggesting that mitotic recombination was the major cause of ROSA26 LOH.
      Dichromatic mouse embryonic cells provide a novel system for studying
      genetic/karyotypic stability and factors influencing expression from allelic
      genes. Similar approaches will allow these phenomena to be studied in tissues.

PMID- 17042953
TI  - Atypically diffuse functional connectivity between caudate nuclei and cerebral
      cortex in autism.
AB  - BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative
      behavior, but also sensorimotor skill learning, oculomotor control, and executive
      functioning. Some of these impairments may be related to abnormalities of the
      caudate nuclei, which have been reported for autism. METHODS: Our sample was
      comprised of 8 high-functioning males with autism and 8 handedness, sex, and age
      matched controls. Subjects underwent functional MRI scanning during performance
      on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI)
      effects were identified as interregional blood oxygenation level dependent (BOLD)
      signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In
      the control group, fcMRI effects were found in circuits with known participation
      of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits).
      Although in the autism group fcMRI effects within these circuits were less
      pronounced or absent, autistic subjects showed diffusely increased connectivity
      mostly in pericentral regions, but also in brain areas outside expected
      anatomical circuits (such as visual cortex). CONCLUSION: These atypical
      connectivity patterns may be linked to developmental brain growth disturbances
      recently reported in autism and suggest inefficiently organized functional
      connectivity between caudate nuclei and cerebral cortex, potentially accounting
      for stereotypic behaviors and executive impairments.

PMID- 17042954
TI  - Novel insights on effect of atrioventricular programming of biventricular
      pacemaker in heart failure--a case series.
AB  - BACKGROUND: Echocardiography plays an integral role in the diagnosis of
      congestive heart failure including measurement of left heart pressure as well as
      mechanical dyssynchrony. METHODS: In this report we describe novel therapeutic
      uses of echo pulsed wave Doppler in atrioventricular pacemaker optimization in
      patients who had either not derived significant symptomatic benefit post
      biventricular pacemaker implantation or deteriorated after deriving initial
      benefit. In these patients atrioventricular optimization showed novel findings
      and improved cardiac output and symptoms. RESULTS: In 3 patients with Cheyne
      Stokes pattern of respiration echo Doppler showed worsening of mitral
      regurgitation during hyperpneac phase in one patient, marked E and A fusion in
      another patient and exaggerated ventricular interdependence in a third patient
      thus highlighting mechanisms of adverse effects of Cheyne Stokes respiration in
      patients with heart failure. All 3 patients required a very short
      atrioventricular delay programming for best cardiac output. In one patient with
      recurrent congestive heart failure post cardiac resynchronization, mitral inflow
      pulse wave Doppler showed no A wave until a sensed atrioventricular delay of 190
      ms was reached and showed progressive improvement in mitral inflow pattern until
      an atrioventricular delay of 290 ms. In 2 patients atrioventricular delay as
      short as 50 ms was required to allow E and A separation and prevent diastolic
      mitral regurgitation. All patients developed marked improvement in congestive
      heart failure symptoms post echo-guided biv pacemaker optimization. CONCLUSION:
      These findings highlight the value of echo-guided pacemaker optimization in
      symptomatic patients post cardiac resynchronization treatment.

PMID- 17042955
TI  - Social support during intensive care unit stay might improve mental impairment
      and consequently health-related quality of life in survivors of severe acute
      respiratory distress syndrome.
AB  - INTRODUCTION: We investigated health-related quality of life (HRQoL) and
      persistent symptoms of post-traumatic stress disorder (PTSD) in long-term
      survivors of acute respiratory distress syndrome (ARDS). We wished to evaluate
      the influence of PTSD on HRQoL and to investigate the influence of perceived
      social support during intensive care unit (ICU) treatment on both PTSD symptoms
      and HRQoL. METHODS: In ARDS patients we prospectively measured HRQoL (Medical
      Outcomes Study 36-Item Short Form; SF-36), symptoms of PTSD (Post-Traumatic
      Stress Syndrome 10-Questions Inventory; PTSS-10), perceived social support
      (Questionnaire for Social Support; F-Sozu) and symptoms of psychopathology
      (Symptom Checklist-90-R); and collected sociodemographic data including current
      employment status. Sixty-five (50.4%) out of 129 enrolled survivors responded, on
      average 57 +/- 32 months after discharge from ICU. Measuring symptoms of PTSD the
      PTSS-10 was used to divide the ARDS patients into two subgroups ('high-scoring
      patients', indicating patients with an increased risk for developing PTSD, and
      'low-scoring patients'). RESULTS: HRQoL was significantly reduced in all
      dimensions in comparison with age- and gender-adjusted healthy controls. Eighteen
      patients (29%) were identified as being at increased risk for PTSD. PTSD risk was
      significantly linked with anxiety during their ICU stay. In this group of
      patients there was a trend towards permanent or temporary disability, independent
      of the period between discharge from ICU and study entry. Perceived social
      support was associated with a reduction in PTSD symptoms (Pearson correlation; p
      < 0.05). Post-hoc test revealed a significant difference between 'high-scoring
      patients' and 'low-scoring patients' with respect to mental health, although they
      did not differ in physical dimensions. CONCLUSION: HRQoL was reduced in long-term
      survivors, and was linked with an increased risk of chronic PTSD with ensuing
      psychological morbidity. This was independent of physical condition and was
      associated with traumatic memories of anxiety during their ICU stay. Social
      support might improve mental health and consequently long-term outcome including
      employment status.

PMID- 17042956
TI  - Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid
      peroxidation end product 4-hydroxynonenal.
AB  - 4-Hydroxynonenal (HNE), a lipid peroxidation end product, is produced abundantly
      in osteoarthritic (OA) articular tissues, but its role in bone metabolism is ill
      defined. In this study, we tested the hypothesis that alterations in OA
      osteoblast metabolism are attributed, in part, to increased levels of HNE. Our
      data showed that HNE/protein adduct levels were higher in OA osteoblasts compared
      to normal and when OA osteoblasts were treated with H2O2. Investigating
      osteoblast markers, we found that HNE increased osteocalcin and type I collagen
      synthesis but inhibited alkaline phosphatase activity. We next examined the
      effects of HNE on the signaling pathways controlling cyclooxygenase-2 (COX-2) and
      interleukin-6 (IL-6) expression in view of their putative role in OA
      pathophysiology. HNE dose-dependently decreased basal and tumour necrosis factor
      alpha (TNF-alpha)-induced IL-6 expression while inducing COX-2 expression and
      prostaglandin E2 (PGE2) release. In a similar pattern, HNE induces changes in
      osteoblast markers as well as PGE2 and IL-6 release in normal osteoblasts. Upon
      examination of signaling pathways involved in PGE2 and IL-6 production, we found
      that HNE-induced PGE2 release was abrogated by SB202190, a p38 mitogen-activated
      protein kinase (MAPK) inhibitor. Overexpression of p38 MAPK enhanced HNE-induced
      PGE2 release. In this connection, HNE markedly increased the phosphorylation of
      p38 MAPK, JNK2, and transcription factors (CREB-1, ATF-2) with a concomitant
      increase in the DNA-binding activity of CRE/ATF. Transfection experiments with a
      human COX-2 promoter construct revealed that the CRE element (-58/-53 bp) was
      essential for HNE-induced COX-2 promoter activity. However, HNE inhibited the
      phosphorylation of IkappaBalpha and subsequently the DNA-binding activity of
      nuclear factor-kappaB. Overexpression of IKKalpha increased TNF-alpha-induced IL
      6 production. This induction was inhibited when TNF-alpha was combined with HNE.
      These findings suggest that HNE may exert multiple effects on human OA
      osteoblasts by selective activation of signal transduction pathways and
      alteration of osteoblastic phenotype expression and pro-inflammatory mediator
      production.

PMID- 17042957
TI  - Accumulation of low density lipoprotein associated cholesterol in calcifying
      vesicle fractions correlates with intimal thickening in thoracic aortas of
      juvenile rabbits fed a supplemental cholesterol diet.
AB  - BACKGROUND: It has been shown that calcifying vesicles play an important role in
      aortic calcification and that cholesterol content in the isolated vesicle
      fraction is increased when rabbits are fed supplemental cholesterol diets.
      Whether lipoprotein-associated cholesterols and other lipids are also increased
      in the vesicle fraction and whether the increase correlates with atherosclerosis
      remain unknown. RESULTS: Fourteen juvenile male rabbits fed an atherogenic diet
      containing 0.5% cholesterol and 2% peanut oil for 3 months developed varying
      degrees of hypercholesterolemia and intimal thickening in the ascending thoracic
      aorta. The correlation between these two parameters was insignificant, and likely
      attributable to the use of small numbers of rabbits in this study. Despite this
      lack of correlation, we demonstrate that the accumulation of cholesterol in
      calcifying vesicle fractions obtained from the collagenase-digested aorta
      fragments correlates well with intimal thickening (r2 = 0.98, p < 0.0001). To a
      smaller degree, the correlation was also significant between intimal thickening
      and the cholesterol accumulation in the microsomal and post-vesicle fractions.
      The cholesterol supplemental diet increased the low density lipoprotein
      cholesterol (LDL-C) content in calcifying vesicle fractions by 3-fold but did not
      affect the triglyceride content. High density lipoprotein-cholesterol (HDL-C) and
      very low-density lipoprotein cholesterol (VLD-C) were absent in calcifying
      vesicle fractions. CONCLUSION: When limited numbers of rabbits are used, LDL-C
      accumulation in calcifying vesicle fractions is a better biomarker for
      atherosclerosis than LDL-C levels in the serum. The close association of LDL-C
      with calcifying vesicles may play an important role in atherosclerosis and
      calcification.

PMID- 17042958
TI  - A framework for protein structure classification and identification of novel
      protein structures.
AB  - BACKGROUND: Protein structure classification plays a central role in
      understanding the function of a protein molecule with respect to all known
      proteins in a structure database. With the rapid increase in the number of new
      protein structures, the need for automated and accurate methods for protein
      classification is increasingly important. RESULTS: In this paper we present a
      unified framework for protein structure classification and identification of
      novel protein structures. The framework consists of a set of components for
      comparing, classifying, and clustering protein structures. These components allow
      us to accurately classify proteins into known folds, to detect new protein folds,
      and to provide a way of clustering the new folds. In our evaluation with SCOP
      1.69, our method correctly classifies 86.0%, 87.7%, and 90.5% of new domains at
      family, superfamily, and fold levels. Furthermore, for protein domains that
      belong to new domain families, our method is able to produce clusters that
      closely correspond to the new families in SCOP 1.69. As a result, our method can
      also be used to suggest new classification groups that contain novel folds.
      CONCLUSION: We have developed a method called proCC for automatically classifying
      and clustering domains. The method is effective in classifying new domains and
      suggesting new domain families, and it is also very efficient. A web site
      offering access to proCC is freely available at
      http://www.eecs.umich.edu/periscope/procc.

PMID- 17042959
TI  - Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides.
AB  - BACKGROUND: Evaluation of microbicides for prevention of HIV-1 infection in
      macaque models for vaginal infection has indicated that the concentrations of
      active compounds needed for protection by far exceed levels sufficient for
      complete inhibition of infection in vitro. These experiments were done in the
      absence of seminal plasma (SP), a vehicle for sexual transmission of the virus.
      To gain insight into the possible effect of SP on the performance of selected
      microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was
      determined. METHODS: The inhibitory activity of compounds against the X4 virus,
      HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator
      cells and quantitated by measuring beta-galactosidase induced by infection. The
      virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP), the
      only microbicide provided in water insoluble, micronized form, in the presence of
      SP was measured. RESULTS: The HIV-1 inhibitory activity of the polymeric
      microbicides, poly(naphthalene sulfonate), cellulose sulfate, carrageenan, CAP
      (in soluble form) and polystyrene sulfonate, respectively, was considerably
      (range approximately 4 to approximately 73-fold) diminished in the presence of SP
      (33.3%). Formulations of micronized CAP, providing an acidic buffering system
      even in the presence of an SP volume excess, effectively inactivated HIV-1
      infectivity. CONCLUSION: The data presented here suggest that the in vivo
      efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might
      become at least partly compromised by the inevitable presence of SP. These
      possible disadvantages could be overcome by combining the respective polymers
      with acidic pH buffering systems (built-in for formulations of micronized CAP) or
      with other anti-HIV-1 compounds, the activity of which is not affected by SP,
      e.g. reverse transcriptase and zinc finger inhibitors.

PMID- 17042960
TI  - Cdt1 revisited: complex and tight regulation during the cell cycle and
      consequences of deregulation in mammalian cells.
AB  - In eukaryotic cells, replication of genomic DNA initiates from multiple
      replication origins distributed on multiple chromosomes. To ensure that each
      origin is activated precisely only once during each S phase, a system has evolved
      which features periodic assembly and disassembly of essential pre-replication
      complexes (pre-RCs) at replication origins. The pre-RC assembly reaction involves
      the loading of a presumptive replicative helicase, the MCM2-7 complexes, onto
      chromatin by the origin recognition complex (ORC) and two essential factors, CDC6
      and Cdt1. The eukaryotic cell cycle is driven by the periodic activation and
      inactivation of cyclin-dependent kinases (Cdks) and assembly of pre-RCs can only
      occur during the low Cdk activity period from late mitosis through G1 phase, with
      inappropriate re-assembly suppressed during S, G2, and M phases. It was
      originally suggested that inhibition of Cdt1 function after S phase in vertebrate
      cells is due to geminin binding and that Cdt1 hyperfunction resulting from Cdt1
      geminin imbalance induces re-replication. However, recent progress has revealed
      that Cdt1 activity is more strictly regulated by two other mechanisms in addition
      to geminin: (1) functional and SCFSkp2-mediated proteolytic regulation through
      phosphorylation by Cdks; and (2) replication-coupled proteolysis mediated by the
      Cullin4-DDB1Cdt2 ubiquitin ligase and PCNA, an eukaryotic sliding clamp
      stimulating replicative DNA polymerases. The tight regulation implies that Cdt1
      control is especially critical for the regulation of DNA replication in mammalian
      cells. Indeed, Cdt1 overexpression evokes chromosomal damage even without re
      replication. Furthermore, deregulated Cdt1 induces chromosomal instability in
      normal human cells. Since Cdt1 is overexpressed in cancer cells, this could be a
      new molecular mechanism leading to carcinogenesis. In this review, recent
      insights into Cdt1 function and regulation in mammalian cells are discussed.

PMID- 17042962
TI  - Neuroaxial anesthesia in a patient with progressive systemic sclerosis : case
      presentation and review of the literature on systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis (SSc), a progressive disease characterized by
      excessive accumulation of connective tissue components. Although most patients
      have long survival, some of them progress rapidly to death. Pulmonary system
      involvement and pulmonary hypertension are the most frequent cause of death. When
      the patient with SSc is to be operated, the anesthetic procedure could be a
      serious problem. In this article, we report a combined spinal--epidural technique
      in a patient with progressive SSc and the anesthetic considerations that could be
      recommended for these patients. CASE PRESENTATION: A 68-year-old woman who had a
      history of progressive systemic sclerosis, pulmonary fibrosis, kyphoscoliosis and
      decreased oral apertura underwent total hip arthroplasty. This operation was
      performed successfully under combined spinal epidural anesthesia. CONCLUSION:
      Systemic sclerosis is a complex disease that involves multiple organ systems.
      Every aspects of anesthetic care may be altered or hindered by the pathogenesis
      of disease. Although the choice of regional or general anesthesia is unclear, to
      choose combined spinal epidural anesthesia may be useful.

PMID- 17042961
TI  - Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line
      induced by human T-cell leukemia virus type 1 Tax protein.
AB  - BACKGROUND: The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1
      protein with the tumor suppressor Dlg1 is correlated with cellular
      transformation. RESULTS: Here, we show that Dlg1 knockdown by RNA interference
      increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as
      measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the
      Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type
      Tax1, but the transformation was minimally affected by Dlg1 reduction. The few
      Tax1DeltaC-transduced CTLL-2 cells that became transformed expressed less Dlg1
      than parental cells, suggesting that Dlg1-low cells were selectively transformed
      by Tax1DeltaC. Moreover, all human T-cell lines immortalized by HTLV-1, including
      the recombinant HTLV-1-containing Tax1DeltaC, expressed less Dlg1 than control T
      cell lines. CONCLUSION: These results suggest that inactivation of Dlg1 augments
      Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are
      critically involved in the transformation.

PMID- 17042964
TI  - Antimicrobial activity of some ethnomedicinal plants used by Paliyar tribe from
      Tamil Nadu, India.
AB  - BACKGROUND: Antimicrobial activity of 18 ethnomedicinal plant extracts were
      evaluated against nine bacterial strains (Bacillus subtilis, Staphylococcus
      aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli,
      Klebsiella pneumonia, Pseudomonas aeruginosa, Ervinia sp, Proteus vulgaris) and
      one fungal strain (Candida albicans). The collected ethnomedicinal plants were
      used in folk medicine in the treatment of skin diseases, venereal diseases,
      respiratory problems and nervous disorders. METHODS: Plants were collected from
      Palni hills of Southern Western Ghats and the ethnobotanical data were gathered
      from traditional healers who inhabit the study area. The hexane and methanol
      extracts were obtained by cold percolation method and the antimicrobial activity
      was found using paper disc diffusion method. All microorganisms were obtained
      from Christian Medical College, Vellore, Tamil Nadu, India. RESULTS: The results
      indicated that out of 18 plants, 10 plants exhibited antimicrobial activity
      against one or more of the tested microorganisms at three different
      concentrations of 1.25, 2.5 and 5 mg/disc. Among the plants tested, Acalypha
      fruticosa, Peltophorum pterocarpum, Toddalia asiatica,Cassia auriculata, Punica
      granatum and Syzygium lineare were most active. The highest antifungal activity
      was exhibited by methanol extract of Peltophorum pterocarpum and Punica granatum
      against Candida albicans. CONCLUSION: This study evaluated the antimicrobial
      activity of the some ethnomedicinal plants used in folkloric medicine. Compared
      to hexane extract, methanol extract showed significant activity against tested
      organisms. This study also showed that Toddalia asiatica, Syzygium lineare,
      Acalypha fruticosa and Peltophorum pterocarpum could be potential sources of new
      antimicrobial agents.

PMID- 17042965
TI  - Endotracheal tube migration following transoesophageal echocardiography probe
      placement in a child.

PMID- 17042963
TI  - High prevalence of ACE DD genotype among north Indian end stage renal disease
      patients.
AB  - BACKGROUND: The Renin-Angiotensin system (RAS) is a key regulator of both blood
      pressure and kidney functions and their interaction. In such a situation, genetic
      variability in the genes of different components of RAS is likely to contribute
      for its heterogeneous association in the renal disease patients. Angiotensin
      converting enzyme-1 (ACE-1) is an important component of RAS which determines the
      vasoactive peptide Angiotensin-II. METHODS: In the present study, we have
      investigated 127 ESRD patients and 150 normal healthy controls from north India
      to deduce the association between ACE gene polymorphism and ESRD. The inclusion
      criteria for patients included a constantly elevated serum creatinine level above
      normal range (ranging from 3.4 to 15.8) and further the patients were recommended
      for renal transplantation. A total of 150 normal healthy controls were also
      genotyped for ACE I/D polymorphism. The criterion of defining control sample as
      normal was totally based on the absence of any kidney disease determined from the
      serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain
      reaction (PCR) based DNA amplification using specific flanking primers Based on
      the method described elsewhere. RESULTS: The difference of DD and II genotypes
      was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI
      = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD
      genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit =
      3.4-8.5). However, no correlation was obtained for different biochemical
      parameters of lipid profile and renal function among DD and non DD genotype.
      Interestingly, approximately 87% of the DD ESRD patients were found hypertensive
      in comparison to the 65% patients of non DD genotype CONCLUSION: Based on these
      observations we conclude that ACE DD genotype implicate a strong possible role in
      the hypertensive state and in renal damage among north Indians. The study will
      help in predetermining the timing, type and doses of anti-hypertensive therapy
      for ESRD patients.

PMID- 17042966
TI  - An unusual adverse effect of an accidental epidural morphine overdose.

PMID- 17042967
TI  - Analgesia for venous cannulation by subcutaneous infiltration: effect of
      lidocaine concentration.

PMID- 17042968
TI  - Securing the airway of a 'super sized' patient: another use for the Aintree
      Catheter.

PMID- 17042969
TI  - 'Spraying the cords'.

PMID- 17042970
TI  - Pancreatitis and hypertriglyceridaemia.

PMID- 17042971
TI  - First national guidelines will help better control HIV/AIDS in China.

PMID- 17042972
TI  - Guidelines for diagnosis and treatment of HIV/AIDS in China (2005).

PMID- 17042973
TI  - Association between Nef-specific CD8 T-cell responses and disease progression in
      HIV-1 subtype B infection.
AB  - BACKGROUND: The correlation between HIV-1 Nef-specific CD8 T-cell responses and
      markers of HIV-1 disease progression still remains unclear. This study analysed
      and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with
      different disease status. METHODS: Two groups of patients with HIV-1 subtype B
      infection were selected according to CD4 count and clinical manifestations: long
      term nonprogressors (LTNPs, n = 20) and advanced progressors (APs, CD4 count <
      500 cells/microl, n = 34). Nef-specific CD8 T-cell responses were studied by
      interferon-gamma ELISpot assay against 3 pools of HIV-Nef peptides. RESULTS: Nef
      specific CD8 T-cell responses did not correlate with viral load or CD4 count in
      all patients and no significant differences were found in the magnitude of Nef
      specific CD8 T-cell responses between groups LTNPs and APs (670 SFC/10(6)
      peripheral blood mononuclear cells vs 1107 SFC/10(6) peripheral blood mononuclear
      cells, P = 0.255). Further comparisons showed that there were also no significant
      correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated
      negatively with viral load (r = -0.397, P = 0.020) and positively with CD4 count
      (r = 0.364, P = 0.034) in group APs. CONCLUSION: These data suggest that
      different correlation patterns between Nef-specific CD8 T-cell responses and
      disease progression exist in LTNPs and APs. Although a negative association was
      observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses
      might fail to play a protective role in different stages of HIV-1 infection.

PMID- 17042974
TI  - Identification of HIV-1 specific T lymphocyte responses in highly exposed
      persistently seronegative Chinese.
AB  - BACKGROUND: Studies of highly exposed persistently seronegative (HEPS)
      individuals may provide valuable information on mechanisms of protection and on
      vaccine design. Cellular immune responses play a critical role in containing
      human immunodeficiency virus. However, the cellular immune responses in HEPS
      individuals have not been thoroughly assessed at the entire viral genome level.
      METHODS: Ten HEPS Chinese with a history of frequent penetrative vaginal
      intercourse (mean frequency, at least once a week), with some unprotected sexual
      contact occurring in the weeks or days immediately before enrollment, 25 HIV-1
      seropositive individuals, 10 HIV-1-seronegative healthy individuals with low-risk
      sexual behavior and no history suggestive of exposure to HIV-1 infection were
      enrolled. HIV-1-specific T cell responses were comprehensively analyzed by an
      interferon-gamma Elispot assay against 770 overlapping peptides spanning all HIV
      1 proteins. RESULTS: HIV-1-specific T-cell responses of interferon-gamma
      secretion were identified in 3 (30%) out of 10 HEPS individuals; the specific
      cytotoxic T lymphocytes were targeted at Pol (2/10), Env (2/10), and Tat (1/10).
      HIV-1-specific T-cell responses of interferon-gamma secretion were identified in
      20 (80%) out of 25 seropositive intravenous drug users (IDUs), revealing that all
      HIV-1 proteins and protein subunits could serve as targets for HIV-1-specific
      CD8(+) T cell responses with 85% recognizing Gag, 80% recognizing Nef, 75%
      recognizing Pol, 60% recognizing Env, 55% recognizing Vpu, 45% recognizing Vpr,
      20% recognizing Vif, 20% recognizing Tat and 15% recognizing Rev in these
      seropositive individuals. None of the seronegative healthy individuals gave the
      positive T-cell responses. CONCLUSIONS: About 30% of HEPS Chinese mounted HIV-1
      specific T cell immune responses. Cell-mediated immunity against HIV-1 may be
      developed through non-productive infections.

PMID- 17042975
TI  - Genetic characterization of three CRF01_AE full-length HIV type 1 sequences from
      Fujian Province, China.
AB  - BACKGROUND: One of the major characteristics of the human immunodeficiency virus
      type 1 (HIV-1) is its unusually high degree of genetic variability, which
      involves in genetic diagnosis, subtyping, vaccine design, and epidemiology. HIV-1
      CRF01_AE is a main prevalent HIV-1 recombinant strain in China. In this study,
      three full-length CRF01_AE genomes from Fujian Province, China were cloned,
      sequenced, and analyzed; and the further genetic diversity defining and
      epidemiologic analysis were carried out. METHODS: Proviral DNA was extracted from
      non-cultured peripheral blood mononuclear cells, the near full-length HIV-1
      genome was amplified and the PCR products were cloned into pCR-XL-TOPO vector and
      sequenced. 5'-long terminal repeat (LTR) and 3'-LTRs were amplified by additional
      independent PCR and cloned into pMD18T vector. Gene-based phylogenic tree was
      constructed and genetic distances were calculated by MEGA 3.1. Simplot was used
      for Bootscan analysis. RESULTS: The phylogeny and genetic distance analysis of
      the three near full-length sequences confirmed that these three samples clustered
      with CRF01_AE isolates, more close to Thailand CRF01_AE strain CM240, and were
      distantly related to African CRF01_AE strain 90CF402. Analysis of their genomic
      organization revealed the presence of nine potential open reading frames. There
      were no major deletions, rearrangements, or insertions in the three sequences,
      but an in-frame stop codon was found in tat gene of Fj051. LTRs of the three
      sequences contained a few nucleotides mutation. We did not find new mosaic
      recombinant in the three sequences. The V3 motif was GPGQ in all the three
      sequences, and there were only few amino acids differences in all three V3 loop
      sequences. CONCLUSION: This report reveals the background of the three full
      length CRF01_AE genomes, the most dominantly circulating HIV-1 strain in Fujian
      Province, China. The work is essential for the design and development of an
      effective AIDS vaccine for the region.

PMID- 17042976
TI  - CD4+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV
      specific CD8+ T cells.
AB  - BACKGROUND: The mechanism of chronic immune activation and impairment of HIV
      specific immune responses during chronic infection is not fully understood.
      However, it is known that high immune activation leads to more rapid progression
      to AIDS. We hypothesize that CD4(+) T cell-mediated viral antigen presentation
      contributes to this pathologic immune activation in HIV-infected individuals.
      METHODS: HIV-specific T cells, responding to noninfectious HIV-1 virions as
      antigen, were measured by flow cytometric assays. These experimental conditions
      reflect the in vivo condition where noninfectious HIV-1 represents more than 99%
      of the antigens. RESULTS: CD4(+) T cells purified from HIV-infected individuals
      were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1
      specific CD8(+) T cells. Cross presentation required the entry of HIV-1 to CD4(+)
      T cells and antigen translocation from endoplasmic reticulum to the Golgi
      complex. Blocking CD4(+) mediated activation of HIV-specific CD8(+) T cells and
      redirecting the viral antigens to antigen presenting cells improved HIV-specific
      T cell responses. CONCLUSIONS: One possible cause of chronic immune activation
      and impairment of HIV-1 specific T cell responses is represented by HIV-1
      harboring CD4(+) T cells cross presenting HIV-1 antigen to activate CD8(+) T
      cells. This new mechanism provides the first evidence that cross presentation of
      noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1
      infection.

PMID- 17042977
TI  - Protection of human islets from induction of apoptosis and improved islet
      function with HO-1 gene transduction.
AB  - BACKGROUND: Islet transplantation represents an ideal therapeutic approach for
      treatment of type 1 diabetes but islet function and regeneration may be
      influenced by necrosis or apoptosis induced by oxidative stress and other
      insults. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the catabolism of
      heme into biliverdin, releasing free iron and carbon monoxide. It has also been
      reported to be an antioxidant enzyme which can improve the function of grafted
      islets by cytoprotection via free radical scavenging and apoptosis prevention. In
      the present study, we investigated whether transduction of HO-1 genes into human
      islets with an adenovirus vector has cytoprotective action on islets cultured in
      vitro and discuss this method of gene therapy for clinical islet transplantation.
      METHODS: Cadaveric pancreatic islets were isolated and purified in vitro.
      Transduction efficiency of islets was determined by infecting islets with
      adenovirus vector containing the enhanced green fluorescent protein gene (Ad
      EGFP) at multiplicities of infection (MOI) of 2, 5, 10, or 20. Newly isolated
      islets were divided into three groups: EGFP group, islets transduced with Ad-EGFP
      using MOI = 20; HO-1 group, transduced with adenovirus vectors containing the
      human HO-1 gene using MOI = 20; and control group, mock transduced islets.
      Insulin release after glucose stimulation of the cell lines was determined by a
      radioimmunoassay kit and the stimulation index was calculated. Flow cytometry was
      used to detect apoptotic cells in the HO-1 group and in the control group after
      induction by recombinant human tumor necrosis factor-alpha (rTNFalpha) and
      cycloheximide (CHX) for 48 hours. RESULTS: Adenovirus vectors have a high
      efficiency of gene transduction into adult islet cells. Transduction of islets
      with the Ad-EGFP was most successful at MOI 20, at which MOI fluorescence was
      very intense on day 7 after transduction and EGFP was expressed in cultured islet
      cells for more than four weeks in vitro. The insulin release in the control group
      was (182.36 +/- 58.96) mIU/L after stimulation by high glucose media (16.7
      mmol/L), while insulin release from the HO-1 group and the EGFP group were
      (270.09 +/- 89.37) mIU/L and (175.95 +/- 75.05) mIU/L respectively. Compared to
      the control group and the EGFP group, insulin release in the HO-1 group increased
      significantly (P < 0.05). After treatment with rTNFalpha and CHX the apoptotic
      ratio of islet cells was (63.09 +/- 10.86)% in the HO-1 group, significantly
      lower than (90.86 +/- 11.25)% in the control group (P < 0.05). CONCLUSIONS:
      Transduction of human islets with Ad-HO-1 can protect against TNF-alpha and CHX
      mediated cytotoxicity. The HO-1 gene also appears to facilitate insulin release
      from human islets. Transduction of donor islets with the adenovirus vector
      containing an HO-1 gene might have potential value in clinical islet
      transplantation.

PMID- 17042978
TI  - Antigen-specific tolerance induced by IL-10 gene modified immature dendritic
      cells in experimental autoimmune myocarditis in rats.
AB  - BACKGROUND: Experimental autoimmune myocarditis (EAM) in rats is a T-cell
      mediated disorder. The initiation and maintenance of autoimmune responses in EAM
      depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic
      immunomodulatory cytokine that functions at different levels of the immune
      response, so it has emerged as a promising therapeutic factor for the treatment
      of autoimmune/inflammatory diseases. This study was designed to test the
      hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells
      (iDCs) ameliorate EAM and to explore the underlying mechanisms. METHODS: EAM was
      induced using the methods of cardiac myosin immunization on day 0 and day 7.
      Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated
      without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was
      analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10
      plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected
      iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were
      injected intravenously for treatment 5 days after the first immunization. On day
      21, HE staining was performed to detect the myocardial inflammation and T
      lymphocyte proliferation assay was used to determine the effects of IL-10 gene
      transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the
      inhibitor of NF-kappaB pathway, was determined by Western blot. RESULTS: BMDCs
      generated in a medium supplemented with granulocyte-macrophage-colony-stimulating
      factor (GM-CSF) were relatively immature, as determined by flow cytometry.
      However, stimulation with LPS induced these cells to become mature (m) DCs with
      higher levels of surface major histocompatibility complex (MHC)-II and
      costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL
      10 transfected iDC, ameliorated the histopathological severity of the myosin
      induced-EAM, and the effect was lost after the DCs underwent maturation induced
      by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen
      specific T cell responses towards cardiac myosin. IkappaB protein was up
      regulated significantly in the IL-10 gene modified iDC group. CONCLUSIONS: IL-10
      gene modified iDC induced antigen-specific tolerance in EAM. The underlying
      mechanisms may be related to costimulatory molecules down-regulation and NF
      kappaB pathway inhibition.

PMID- 17042979
TI  - Microsurgical treatment of craniopharyngiomas: report of 284 patients.
AB  - BACKGROUND: Generally, total surgical removal of craniopharyngioma results in
      satisfactory outcome with a low recurrence rate, however, the location of the
      tumor and its adherence to the hypothalamic structures can make the operation
      difficult. The goal of the present study was to assess the outcome of
      craniopharyngiomas in 284 patients treated surgically. METHODS: A total of 284
      patients (151 men and 133 women) with craniopharyngioma were treated surgically
      by our neurosurgeons from January 1996 to March 2006. Among them, 226 (79.6%)
      patients were adults (15 years of age or older; mean, 35.8 +/- 10.6), 58 (20.4%)
      were children (14 years of age or younger; mean, 9.1 +/- 3.8). The diameter of
      the tumors were 2.0 - 9.0 cm (mean, 36.54 +/- 11.4). The tumors were classified
      into the superior (23 patients) and inferior ventricular (261) types according to
      the location of the tumor relative to the third ventricular floor. For the
      patients with craniopharyngioma of inferior ventricular type, pterional approach
      was used in 191 (67.3%) patients, subfrontal approach in 17 (6.0%), and
      translamina terminalis through frontobasal interhemispheric approach in 53
      (18.7%). For those with the tumors of superior ventricular type, transcallosal
      approach into the anterior third ventricle was done in 10 (3.5%) patients, and
      the lamina terminalis approach in 13 (4.6%). Of the 284 patients, 204 (71.8%)
      were followed up for 0.5 to 8 years (mean, 2.1 +/- 1.8), including 162 patients
      received total tumor removal, and 37 underwent subtotal or partial removal.
      RESULTS: Total, subtotal and partial removal of the tumors were achieved in 237
      (83.5%), 34 (12.0%) and 13 (4.5%) patients, respectively. The pituitary stalk was
      preserved in 176 (62.0%) patients, severed in 52 (18.3%), and unidentified in 56
      (19.7%). Twelve (4.2%) patients died within one month after the surgery. During
      the follow-up, 23 (14.1%) patients experienced tumor recurrence 1.0 - 3.5 years
      (mean, 1.8 +/- 1.6) after total tumor removal, and 24 (64.9%) had recurrent tumor
      0.25 - 1.5 years (mean, 0.5 +/- 0.4) after subtotal or partial resection. Normal
      activities of daily living were regained in 63 (80%) patients, independence in 29
      (14.2%), and daily life with assistance in 9 (4.4%). Four (2.0%) patients died
      0.9 - 3 years (mean, 1.6 +/- 1.4) after discharge from hospital, 3 of them died
      of hypothalamic deficiency. CONCLUSIONS: We can protect the hypothalamic
      structures and its perforating arteries by choosing surgical approaches according
      to the location of craniopharygioma relative to the third ventricular floor. The
      mortality, morbidity, and recurrence rate in patients received total resection
      are lower than those of patients underwent subtotal or partial resections. In
      addition, preservation of the pituitary stalk is critical when total tumor
      resection is feasible.

PMID- 17042980
TI  - Vascular endothelial growth factor expressing mesenchymal stem cells improves
      cardiac function in chronic myocardial infarction in pigs.

PMID- 17042981
TI  - Teaching chronic obstructive airway disease patients using a metered-dose
      inhaler.

PMID- 17042982
TI  - [Lipid lowering goals in high risk and very high cardiovascular risk patients: a
      reasonable challenge?].
AB  - OBJECTIVE: The last modifications of the National Cholesterol Education Program
      (NCEP) indicate some lower therapeutic targets of low density protein cholesterol
      (LDL-c) in patients with very high vascular risk. Our study aims to establish the
      degree of compliance of the therapeutic targets defined by these modifications.
      PATIENTS AND METHOD: Descriptive and cross sectional study of patients from a
      cardiovascular clinic. Low-density lipoprotein cholesterol (LDL-c) was calculated
      and targets were established according the new update of NCEP-ATP III. RESULTS:
      836 patients, 625 (75%) with HR and 211(25%) with VHR were studied 45% of HR and
      67% of VHR were receiving treatment with statins (p < 0.001) but only 38% of HR
      and 15% of VHR achieved target LDL-c levels. The percentage of patients who could
      achieve LDL-goals using the maximum approved dose of the statins plus other lipid
      lowering drug was calculated: The 31% of HR and 51% of VHR were unable to achieve
      the LDL-c targets. CONCLUSIONS: Only 15% of very high risk patients achieve
      target levels of LDL-c according to the new NCEP-ATP III recommendations. Even
      using maximum dose of statins in combination with other lipid lowering drugs,
      less than half of the patients will be able to achieve LDL-c goal (< 70 mg/dl).

PMID- 17042983
TI  - [Analysis of the characteristics of patients with bladder cancer diagnosed of
      multiple neoplasms in the health district of Leon (Spain)].
AB  - OBJECTIVE: We analyzed the characteristics of the patients with bladder neoplasms
      who developed a multiple malignant primary neoplasm (MMPN) in the health district
      of Leon, the impact on survival and the prognostic variables. MATERIAL AND
      METHODS: We have used the data from the Tumor Registry of the Hospital of Leon
      and selected all those patients who were diagnosed of a bladder tumor between
      1993 and 2002. They were classified into two groups: the first with 71 patients
      with MMPN and a second group with 159 patients with single bladder tumors
      diagnosed between 1996 and 1997. RESULTS: Incidence of MMPN was of 7.1 percent.
      More than half of the patients had familial oncologic background. The second most
      frequently diagnosed neoplasms were urologic, followed by gastrointestinal and
      respiratory. Survival of patients with MMPN was 21 percent lower than single
      neoplasms. Variables with prognosis significance were the stage of the second
      neoplasm, diagnosis of a second urologic neoplasm and surgery treatment for the
      second tumor. CONCLUSIONS: MMPN in patients with bladder tumors are frequent in
      our geographic area. The high frequency of familial oncologic antecedents in
      these patients suggest a genetic background. Prognosis of MMPN patients is worse
      than single tumors patients, but no differences were observed regarding prognosis
      in patients with synchronous or metachronous MMPN.

PMID- 17042984
TI  - [Effectiveness of a quality improvement intervention in blood pressure control in
      Primary Care].
AB  - INTRODUCTION AND OBJECTIVES: To evaluate the effectiveness of a quality
      improvement intervention on professionals sanitary in blood pressure control in
      hypertensive patients. METHODS: Quality improvement trials with cuasi
      experimental design. Two primary care health centres. One centre was assigned
      intervention group (7 family doctors and 419 patients) and the other was control
      group (7 family doctors and 419 patients). The quality improvement intervention
      consisted of a combined program comprising audit, feedback, training sessions
      about main hypertension clinical guidelines during 6 months. The main measurement
      were blood pressure, lipid levels, diabetes, smoking and body index mass,
      antihypertensive drugs and record treatment adherence and therapeutic plan in
      march 2002 the baseline measurement and march 2004 the post intervention.
      RESULTS: In study group blood pressure systolic and diastolic decreased 8.16/3.71
      mmHg and control group increased 1.56/0.13 mmHg, respectively. The intervention
      effect was a drop of 9.72 mmHg (IC 95%: 7.50-11.94) and diastolic blood pressure
      in 3.84 mmHg (IC 95%: 2.40-5.28). The rate of hypertensive patients with blood
      pressure < 140/90 mmHg increased from 37.5% to 68.8% in study group, without
      changes in control group (p < 0.05). The drugs and combination drugs prescribed
      increased in both group, while the records of therapeutics plans and adherence
      increased only in intervention group (p < 0.05). CONCLUSIONS: The quality
      improvement intervention was associated to a systolic and diastolic blood
      pressure reduction and a increase of rate patients with blood pressure
      controlled.

PMID- 17042985
TI  - [COPD, a public health problem].
AB  - The fundamental etiologic factor of COPD is tobacco. This has a 9% prevalence in
      Spain and although this rate is underestimated according to the last studies,
      COPD generates about 39,000 hospital admissions per year. It has a re-admission
      rate between 12% and 32%, infections being the fundamental cause. The average
      care cost per patient from its diagnostic to death is 27,500 euro and we should
      add a high percentage of employee absenteeism. Due to its chronic aspect, high
      health care cost and possible improvement of the quality of life of patient, the
      solution to the problem needs to have a more active involvement of the doctor who
      attends these patients.

PMID- 17042986
TI  - [Data and reflections on the current process of the multicenter clinical trial
      assessment in Spain].
AB  - The European Directive 2001/20/EC was intended, among other things, to simplify
      and accelerate the start of multicenter clinical trials (MCT) in all European
      Union countries. The Spanish regulation in force since May 2004 has failed to
      achieve this. Because there is not a real single opinion in Spain, as given by a
      single Research Ethics Committee, a key point to accelerate the MCT assessment,
      less than 50% of the protocols are assessed in the maximum time of 60 days
      established by the Directive. As a consequence in 2005 up to 29% of investigators
      (twice as much as in 2003 percentage) had no time to recruit patients in the MCT,
      since when the ethical-administrative process is finally completed, the
      recruitment period has almost concluded, or even has finalized internationally.
      Likewise, a 37% reduction in the percentage of investigators recruiting > 90% of
      committed cases in MCT was observed between 2003 and 2005. All these differences
      are statistically significant (p < 0.0001). These figures clearly show that Spain
      needs urgent changes in the current regulation of MCT to be competitive in
      clinical research in Europe.

PMID- 17042987
TI  - [Classification criteria and clinical significance of the metabolic syndrome].
AB  - The metabolic syndrome (MS) is a multifactorial entity (genetic and behavioral).
      Its incidence and prevalence have risen dramatically, especially in Western
      countries, where lifestyle is changing (high caloric intake of mostly saturated
      fat, heavy alcohol consumption, smoking and little physical activity). It results
      from the striking increase prevalence of obesity and is an increasingly
      recognized factor for cardiovascular risk. The MS is defined in various ways. The
      most recent NCEP and IDF definitions are simple and easy to use in clinical
      practice. Nevertheless, a unique worldwide definition is still needed, as these
      definitions show significant differences in some ethnic groups.

PMID- 17042988
TI  - [Generalized seizure episode of metabolic origin].

PMID- 17042989
TI  - [Extrapleural lesion in right upper lobe associated to lytic lesion of the fifth
      right rib].

PMID- 17042990
TI  - [Ungual alterations in patient with edemas in lower limbs].

PMID- 17042991
TI  - [35 year old male with lumbar pain and fever after intravenous cocaine
      consumption].

PMID- 17042992
TI  - [Deep venous thrombosis of left arm and multiple enlarged lymph nodes].

PMID- 17042993
TI  - [Persistent leukocytosis and hyperglycemia].

PMID- 17042994
TI  - [Cyclosporine A in treatment of lupus nephritis resistant to cyclophosphamide and
      mycophenolate mofetil: a case report].

PMID- 17042995
TI  - [Hepatobiliary fasciolasis without eosinophilia].

PMID- 17042996
TI  - [Metabolic bone disease: something more than medication].

PMID- 17042997
TI  - [Vitamin D deficit as cause of latent tetany].

PMID- 17042998
TI  - [Diaphragmatic hernia of Morgagni in the adult].

PMID- 17042999
TI  - [Multidisciplinary access to Intensive Care Medicine].

PMID- 17043000
TI  - [Doss porphyria without demonstrated enzyme deficit: a secondary porphyrinuria?].

PMID- 17043001
TI  - [Fabry disease in Spain: first analysis of the response to enzyme replacement
      therapy].
AB  - BACKGROUND AND OBJECTIVE: Fabry disease is a X-linked lysosomal disorder caused
      by a deficient activity of the enzyme alfa-galactosidase A. Lack of enzyme
      activity results in progressive accumulation of globotriaosylceramide (Gb3)
      leading to multiorgan dysfunction and early death. Enzyme replacement therapy
      (ERT) has recently become available and the database Fabry Outcome Survey (FOS)
      of Spain gives us the opportunity to asses the efficacy of this therapy. Our
      objective is to describe the safety and the effects on renal, cardiac and
      neurological (pain) aspects of ERT with agalsidase alfa. PATIENTS AND METHOD: The
      effects of 1, 2, 3 and 4 years of ERT with agalsidase alfa on renal function
      (assessed by estimated glomerular filtration rate), proteinuria, heart size
      (assessed by echocardiography), arrhythmias, cardiac valvular anomalies and pain
      (assessed by the need of concomitant pain therapy) were analyzed in 33 patients
      under treatment. Safety of ERT was assessed by the reported infusion-related
      reactions in FOS. RESULTS: Overall, treatment with agalsidase alfa stabilized
      renal function, but the final result depends on the onset of ERT: there is a
      tendency to stabilization of renal function in those patients with mild
      deterioration of renal function, a tendency to improve in those patients with
      moderate deterioration and to worse in those with severe deterioration of renal
      function. Proteinuria and left ventricular heart size also estabilized under ERT,
      and pain improved. TSE infusion-related reactions occurred with an incidence of
      0.7%. CONCLUSIONS: ERT with agalsidase alfa is safe and stabilized the abnormal
      clinical parameters observed in patients with Fabry disease.

PMID- 17043002
TI  - [Linguistic adaptation and Spanish validation of the LANSS (Leeds Assessment of
      Neuropathic Symptoms and Signs) scale for the diagnosis of neuropathic pain].
AB  - BACKGROUND AND OBJECTIVE: This study was intended to achieve a linguistic
      adaptation and validation into Spanish of the LANNS scale for the differential
      diagnosis of neuropathic pain. MATERIAL AND METHOD: Cross-sectional validation
      study carried out in two phases: first, cultural adaptation into Spanish
      language, by means of a conceptual equivalence approach, including forward and
      backward translations in duplicate and review by experts; and second, validation
      study of the scale in patients with neuropathic, noniceptive and mixed pain, in
      which the scale properties of reliability (internal consistency and inter-rater
      agreement with kappa and intra-class correlation coefficients) and validity (ROC
      curves analisys, agreement with reference diagnosis and determination of
      sensitivity, specificity and positive and negatives predictive values) were
      evaluated. RESULTS: A total of 156 subjects (90 women, 58.4%), 89 with pain of
      neuropathic origin (mean age [SD], 59.6 [19.4] years, 22 with mixed pain due to
      radiculopathy) and 67 with nociceptive pain (66.6 [11.8] years) were included in
      the study. Diagnosis of the type of pain was performed by standard clinical
      criteria. The scale was administrated by trained interviewers, in duplicate and
      blinded to the reference diagnosis. The scale showed good reliability (internal
      consistency: Cronbach and Guttman split-half coefficients between 0.68 and 0.71;
      inter-rater agreement: kappa coefficient of 0.70 and intra-class correlation
      coefficients between 0.77 and 0.92) and validity for a cut-off value > or = 12
      points, which represented the best value to discriminate between patients with
      neuropathic and nociceptive components of pain (kappa coefficient = 0.70; CI 95%,
      0.59-0.81; p < 0.0001); area under the curve, 0.929; (p < 0.0001); specificity,
      89.4% (CI 95%, 79.4%-95.6%) and positive value, 91.1%; CI 95%, 82.6%-96.4%).
      CONCLUSIONS: The Spanish version of the LANSS scale is reliable and valid for the
      differential diagnosis of neuropathic pain.

PMID- 17043003
TI  - [Usefulness of a new index for mortality after hospitalization in adults older
      than 70 years].
AB  - BACKGROUND AND OBJECTIVE: Walter et al developed and validated a mortality
      prognostic index in older adults after hospitalization. Our objective was to
      evaluate the Walter index utility and to compare it with Charlson index and
      Barthel index in our population. PATIENTS AND METHOD: 455 patients were included
      (224 men and 231 women), medium age was 81.4 years (range: 70-99), who were
      discharged from 4 hospitals in Barcelona. At the moment of discharge Barthel
      index, Charlson index and Walter index were administered. RESULTS: One year after
      discharge the mortality was 40.66%. Medium Barthel index (standard deviation) was
      64.42 (35.66), medium Charlson index was 3.07 (1.87), and medium Walter index was
      5.34 (2.97). ROC curves analysis was done and it shows the bigger area under the
      curve was Walter index (0.691). CONCLUSIONS: It's proved the Walter index utility
      for mortality prognostic one year after discharge in elderly people who are
      admitted in our hospitals. This could be useful to make a care design and
      therapeutic objectives.

PMID- 17043004
TI  - [Behcet disease].

PMID- 17043005
TI  - [Neurological complications of celiac disease].

PMID- 17043006
TI  - [Linoleic conjugated acid: current interest in human nutrition].
AB  - Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of
      linoleic acid. The major dietary sources of CLA are meat from rumiants and dairy
      products. There are also foods enriched in CLA (by modification animal feed or
      addition of commercial CLA from cartamo oil). However, the major isomer of CLA in
      natural food is cis-9,trans-11 and commercial CLA contains approximately equal
      amounts of cis-9,trans-11 and trans-10,cis-12 isomers. Although CLA is minor
      component of the diet, at present CLA has provoked intense scientific research
      accompanied by an advertising boom. This is due to the potential health effects
      demonstrated in animal and cell culture experiments including effects on body
      composition, specially a reduction in body fat mass and anticarcinogenic,
      antidiabetogenic and immune modulating effects. The results obtained in human
      volunteers are limited and even sometimes contradictory. This review focuses on
      recently studies in humans. To draw conclusions on CLA's potential interest as a
      functional ingredient, additional studies are needed to clearly define optimal
      level of CLA intake, short and long term effects and side effects of each
      individual CLA isomer in order to determine its safety and efficacy.

PMID- 17043007
TI  - [Active hemosurveillance: a system that evaluates those post-transfusional
      adverse effects that are not detected by the conventional hemosurveillance
      system].

PMID- 17043008
TI  - [Management of heart failure in short stay medical unit: mean stay, frequency and
      predictors of readmission].

PMID- 17043009
TI  - [Carbamazepine intoxication in a HIV patient under artiretroviral therapy].

PMID- 17043010
TI  - [Hypogammaglobulinemia secundary to actinic enteritis].

PMID- 17043011
TI  - [Liver abscess by Salmonella within a metastases of mullerian uterin cancer].

PMID- 17043012
TI  - [Visceral leishmaniasis with cardiac affectation in an immunocompetent patient].

PMID- 17043013
TI  - JAK2V617F mutations as cooperative genetic lesions in t(8;21)-positive acute
      myeloid leukemia.
AB  - Significant progress has been made in identifying genetic lesions that are
      causally implicated in the pathogenesis of acute myeloid leukemia (AML). These
      insights improve our understanding of the genetic basis of the disease, a
      prerequisite for the development of novel therapeutic approaches.

PMID- 17043014
TI  - Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an
      EORTC cohort study.
AB  - BACKGROUND AND OBJECTIVES: Second cancer has been associated with non-Hodgkin's
      Lymphoma (NHL) treatment, but few studies have addressed this issue considering
      specific treatments. DESIGN AND METHODS: We estimated risk by standardized
      incidence ratios (SIR) and absolute excess risk (AER) based on general population
      rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years)
      treated for aggressive NHL in four successive EORTC (European Organization for
      Research on Treatment of Cancer) trials. RESULTS: All patients received fully
      dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14%
      high-dose treatment. Half of the patients needed salvage treatment and 37% were
      followed for more than 10 years. The cause of death was NHL in 79% of the
      patients; 4% died of second cancer (median survival 8.9 (0.8- 20.5) years).
      Cumulative incidences (death from any cause being a competing event) were 5% and
      11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic
      syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in
      young patients high risks were observed for leukemia (SIR 16.7,95% CI 1.4
      93.1,AER 5.0), Hodgkin's lymphoma (SIR 60.1,95% CI 12.4-175.2, AER 15.7),
      colorectal cancer (SIR 12.5, 95% CI 2.6-36.5, AER 14.7) and lung cancer (SIR
      15.4; 95% CI 4.2-39.4, AER 19.8), while risk in patients older than 45 years
      matched than that in the normal population. The risk of cancer was significantly
      raised by smoking and salvage treatment. INTERPRETATION AND CONCLUSIONS: Half of
      the patients die of aggressive NHL before living long enough to experience second
      cancer. Only young patients have a high risk of second cancer during follow-up
      beyond 10 years.

PMID- 17043015
TI  - The activity and toxicity of low dose clofarabine against relapsed or refractory
      myeloma.
AB  - Eight patients with refractory multiple myeloma were treated with clofarabine 4
      mg/m2/day on days 1-5 of a 28 day cycle. No objective evidence of anti-myeloma
      activity was observed (median time to progression of 52 days). All patients
      experienced grade 3-4 neutropenia and a greater than 50% decrease in platelet
      counts during treatment.

PMID- 17043016
TI  - The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: Patients with acute myeloid leukemia are at risk of
      bleeding. The risk factors for different severities of bleeding are poorly
      studied. DESIGN AND METHODS: Data from Rebulla et al. were analyzed in an
      exploratory analysis using multivariate Cox regression analyses for time-to-first
      bleed with time-depend- ent covariates reflecting measures of clinical and
      laboratory variables on the previous day. The relationships of the variables with
      three bleeding categories were studied: mild bleeding (WHO grades 1 and 2)
      clinically significant (bleeding grades 2, 3 and 4) and severe (bleeding grades 3
      and 4). RESULTS: Bleeding of any severity occurred in 149 (58.4%) of 255
      patients. There were 743 days of bleeding over 7335 patient-days of observation.
      Risk factors for mild bleeding included increased body temperature and decreased
      platelet count; the risk was decreased with administration of antifungal
      medication or platelet transfusion on the previous day. Risk factors for
      clinically significant bleeding included grade 1 bleeding on the previous day,
      decreased platelet count and elevated body temperature. Decreased platelet count
      and mild bleeding on the previous day were risk factors for severe bleeding.
      Higher hemoglobin values were associated with a delay in the time-to-first
      clinically significant bleed. INTERPRETATION AND CONCLUSIONS: These results
      support clinical guidelines for increasing the platelet transfusion threshold in
      the presence of fever and support the use of milder bleeding symptoms as an
      outcome in clinical trials. The suggestion that hemo- globin concentration maybe
      predictive of bleeding risk supports the hypothesis that this maybe a valuable
      intervention in anemic thrombocytopenic patients at high risk of bleeding.

PMID- 17043017
TI  - CARMA1 and chromosomal translocations in extranodal marginal zone B-cell
      lymphomas of MALT type or diffuse large B-cell lymphomas.
AB  - We analyzed the configuration of the CARMA1 gene, encoding a protein that closely
      interacts with BCL10 and MALT1, in a series of 120 extranodal marginal zone B
      cell lymphomas of MALT-type and 35 diffuse large B-cell lymphomas. Our study
      suggests that CARMA1 is not targeted by chromosomal translocations in these
      lymphoma entities.

PMID- 17043018
TI  - Quantitative assessment of the transcriptional impact of mutations in the
      3'untranslated region of the human beta-globin gene: application to the +1480 C-
      >G mutation.
AB  - The +1480 C -->G mutation in the 3' untranslated region (UTR) of the human beta
      globin gene has been associated with beta-thalassemia. A previously vali- dated
      in vitroexpression model used to assess the transcriptional impact of this 3'UTR
      mutation demonstrated that it has no effect on beta-globin gene expression.

PMID- 17043019
TI  - Identification of risk factors in atypical chronic myeloid leukemia.
AB  - In the WHO classification atypical chronic myeloid leukemia (CML) has been
      considered as a new distinct clinical entity included in the category of mixed
      myeloproliferative/myelodysplastic disorders. Little is known about this uncommon
      disease, whose incidence is about of one-two cases every 100 cases of Ph-positive
      CML. We analyzed our series of 55 patients diagnosed as having aCML, with the aim
      of identifying clinical factors of possible prognostic value on survival and
      acute transformation.

PMID- 17043020
TI  - Concomitant aberrant overexpression of RUNX1 and NCAM in regenerating bone marrow
      of myeloid leukemia of Down's syndrome.
AB  - BACKGROUND AND OBJECTIVES: Myeloid leukemia of Down's syndrome (ML-DS) has
      characteristic biological features (e.g. expression of the truncated GATA1s),
      which are different from those of non-DS childhood acute myeloid leukemias (AML).
      The objective of this study was to investigate factors predisposing to the
      development of ML-DS. DESIGN AND METHODS: We analyzed 134 bone marrow specimens
      from 64 children with ML-DS and non-DS AML during chemotherapy and 7 specimens
      from DS children with- out leukemia,who did not receive any chemotherapy,The
      specimens were analyzed by multiparameter flow cytometry and quantitative reverse
      transcriptase polymerase chain reaction for transcription factors involved in
      hematopoiesis. RESULTS: Samples taken from children with ML-DS in complete
      remission during chemotherapy aberrantly expressed CD56 (NCAM) at the surface of
      monocytic and granulocytic cells. Compared to non-DS AML cases,children with ML
      DS had a statistically significant higher proportion of CD56+ cells in the CD33+
      fraction: 71%+/-6% vs. 4%+/-1% (p<0.00001). A significant decrease of the amount
      of CD33+/CD56+ cells was observed during and after maintenance therapy. An
      increased number of CD33+/CD56+ cells was also present (>85%) in children with DS
      who did not receive chemotherapy, but showed a left-shift (due to infection),
      compared with DS children without left-shift (<10% CD33+/CD56+ cells). Within the
      CD33+/CD56+ fraction, RUNX1 was overexpressed more than 5-fold (p<0.02) compared
      to CD33+/CD56- cells, whereas there were no differences regarding GATA1, SPI1,
      ERG or ETS-2 levels. INTERPRETATION AND CONCLUSIONS: The combined overexpression
      of RUNX1 and NCAM during stress hematopoiesis in children with DS might be a key
      factor in the development of overt leukemia and/or in the growth advantage of the
      malignant GATA1s clone in ML- DS.

PMID- 17043021
TI  - The expression of PRDI-BF1 beta isoform in multiple myeloma plasma cells.
AB  - The PRDM1 gene, a master regulator of plasma cells (PC), can generate two
      transcription factor isoforms: PRDI-BF1alpha and PRDI-BF1beta. The present study
      shows that purified human normal PC have a significantly lower levels of PRDI
      BF1beta expression than that in tumoral PC isolated from multiple myeloma (MM)
      (0.06+/-0.01 and 0.25+/-0.05, respectively; p<0.001). The role of this finding in
      MM is discussed.

PMID- 17043022
TI  - Diagnosis and treatment of vitamin B12 deficiency--an update.
AB  - We represent an update on diagnosing and treatment of vitamin B12 deficiency.
      Vitamin B12 deficiency should be suspected in all patients with unexplained
      anaemia and/or neurological symptoms,as well as in patients at risk of developing
      vitamin B12 deficiency such as the elderly and patients with intestinal diseases.
      Measurement of plasma cobalamins is suggested as the primary analysis followed by
      measurement of plasma methylmalonic acid in unsettled cases. Accumulating
      evidence indicates that the biologically active cobalamin,plasma
      holotranscobalamin (holoTC),may be superior to plasma cobalamins, and measurement
      of holoTC is currently introduced in the clinical setting. No consensus exists
      concerning evaluation of the cause for vitamin B12 deficiency,and pros and cons
      on the different tests mainly aiming at evaluation of the function of the gastric
      mucosa are presented. Once the diagnosis of vitamin B12 deficiency has been
      confirmed efficient treatment can be ensured either by injections every 2-3 month
      or by a daily dose of 1 mg vitamin B12.

PMID- 17043023
TI  - The association of increased p14ARF/p16INK4a and p15INK4a gene expression with
      proliferative activity and the clinical course of multiple myeloma.
AB  - p14/p16 and p15 gene expression was assessed by quantitative polymerase chain
      reaction in purified plasma cells (PC) from 52 patients with symptomatic multiple
      myeloma (MM) and seven with smoldering MM in order to clarify the impact of these
      genes on the proliferative activity of tumor cells and patients' outcome. p15
      expression was lower in symptomatic MM than in smoldering SMM (-1.80
      vs.1.51,p=0.026); similar results were observed for p14/p16. MM patients whose PC
      displayed high p15 and/or p14/p16 expression had a lower percentage of S-phase PC
      than the remaining cases (1.79%+/-1.35 vs. 3.04%+/-1.42, p=0.028), favorable
      prognostic factors and longer survival (100% vs. 49%at 2.5 years; p=0.007).

PMID- 17043024
TI  - A comparison of the in vitro cytotoxicity of daunorubicin and liposomal
      daunorubicin in pediatric acute leukemia.
AB  - Anthracyclines are effective in the treatment of leukemia, but their use is
      limited because of cardiotoxicity. Liposomal daunorubicin (L-DNR) is potentially
      less cardiotoxic than daunorubicin (DNR). We compared in vitro cytotoxicity in
      pediatric acute leukemia samples and found no significant differences between
      cytotoxicity of DNR and L-DNR.

PMID- 17043025
TI  - Bortezomib plus dexamethasone as induction treatment prior to autologous stem
      cell transplantation in patients with newly diagnosed multiple myeloma: results
      of an IFM phase II study.
AB  - BACKGROUND AND OBJECTIVES: Induction regimens prior to autologous stem cell
      transplantation (ASCT) in newly diagnosed multiple myeloma patients usually
      result in complete remission (CR) rates of <10%. The use of novel agents may
      increase the CR rate before ASCT, which may improve post-transplantation response
      and survival. DESIGN AND METHODS: This was a phase II, open-label trial of
      bortezomib (1.3 mg/m(2), days 1,4,8,11) and dexamethasone (40 mg,days 1-4 and 9
      12 for cycles 1-2,days 1-4 for cycles 3-4) administered for four 21-day cycles as
      induction therapy in chemotherapy-naive myeloma patients. RESULTS: Of 52
      recruited patients, 48 were eligible for the study. The overall response rate was
      66% including 21% CR and 10% very good partial remission (>90% reduction of the M
      component). Four patients had a minimal response, six had stable disease and five
      had progression. One patient died after salvage therapy with VAD. The most common
      side effects were gastrointestinal symptoms, peripheral neuropathy, and fatigue.
      These were usually mild. Peripheral neuropathy was observed in 15 cases but was
      grade 2-3 in only seven cases (14%). There was no deep vein thrombosis and no
      hematologic toxicity greater than grade 2. Grade 3 infections were recorded in
      five patients including three who had herpes zoster infections. Stem cell
      collection was programmed in 44 cases and all patients had sufficient CD34+ cells
      to perform one ASCT (> 2 x 10(6)/kg). INTERPRETATION AND CONCLUSION: This regimen
      of bortezomib plus dexamethasone appears effective and well tolerated in newly
      diagnosed myeloma patients.

PMID- 17043026
TI  - The effect of silencing NKG2D through RNA interference on receptor functions in
      interleukin-2-activated human natural killer cells.
AB  - Natural killer (NK) cells are effectors of the innate immunity involved in tumor
      surveillance. NKG2D is a potent activating receptor eliciting cytokine and
      cytolytic NK responses upon recognition of tumor-associated ligands. We
      engineered primary interleukin (IL)-2-activated human NK cells to express
      constitutively low levels of NKG2D by lentiviral delivery of small interfering
      RNA. NKG2D-mediated effector functions were strongly impaired in NKG2D(low) NK
      cells. Reduction of NKG2D surface expression to 15%, corresponding to receptor
      levels in resting NK cells, rendered cells fully insensitive to NKG2D triggering.
      These data underscore the importance of NKG2D receptor cell surface density and
      suggest a threshold of expression for optimal reactivity of human NK cells.

PMID- 17043027
TI  - CD52 expression patterns in myeloma and the applicability of alemtuzumab therapy.
AB  - Alemtuzumab has been proposed as a therapeutic agent in myeloma. CD52 was
      detected on plasma cells in 46/106 patients but levels were 30-fold lower than on
      alemtuzumab-responsive cells (n=138) and 8-fold lower than on alemtuzumab
      resistant cells (n=57). The data suggest that myeloma plasma cells are unlikely
      to be depleted by alemtuzumab in most patients.

PMID- 17043029
TI  - Balancing within various discourses--the art of being old and living as a Sami
      woman.
AB  - The aim of this part of the Umea 85+ Study was to explore how indigenous women
      narrate their lives and their experience of being old as Sami women. Interviews
      with 9 old Sami women were analyzed using grounded theory. The categories
      identified were "reindeer as the basis of life," "longing for significant Sami
      values," "feeling valued as a Sami woman," and "changing for survival;" these
      evolved into the core category: "balancing within various discourses-the art of
      being old and living as a Sami woman." Knowing how to balance provided the
      ability to make use of available opportunities.

PMID- 17043030
TI  - Review: Takagi-Sugeno fuzzy modeling of skin permeability.
AB  - The skin is a major exposure route for many potentially toxic chemicals. It is,
      therefore, important to be able to predict the permeability of compounds through
      skin under a variety of conditions. Available skin permeability databases are
      often limited in scope and not conducive to developing effective models. This
      sparseness and ambiguity of available data prompted the use of fuzzy set theory
      to model and predict skin permeability. Using a previously published database
      containing 140 compounds, a rule-based Takagi-Sugeno fuzzy model is shown to
      predict skin permeability of compounds using octanol-water partition coefficient,
      molecular weight, and temperature as inputs. Model performance was estimated
      using a cross-validation approach. In addition, 10 data points were removed prior
      to model development for additional testing with new data. The fuzzy model is
      compared to a regression model for the same inputs using both R2 and root mean
      square error measures. The quality of the fuzzy model is also compared with
      previously published models. The statistical analysis demonstrates that the fuzzy
      model performs better than the regression model with identical data and
      validation protocols. The prediction quality for this model is similar to others
      that were published. The fuzzy model provides insights on the relationships
      between lipophilicity, molecular weight, and temperature on percutaneous
      penetration. This model can be used as a tool for rapid determination of initial
      estimates of skin permeability.

PMID- 17043032
TI  - Subacute inhalation toxicity of 2-chloro-4-toluidine in rats.
AB  - This article addresses results from a 4-wk inhalation exposure study in Wistar
      rats with the vapor and/or aerosol atmospheres of 2-chloro-4-toluidine. Groups of
      10 rats/sex were nose-only exposed to mean analytical concentrations of 19.1,
      115.1, and 702.3 mg/m3 using an exposure regimen of 6 h/day and 20-22 exposures
      within a time period of 4 wk. These concentrations were selected based on results
      from a repeated 5 x 6 h/day pilot study using concentrations of 27.1, 104.8,
      381.6, and 1283.7 mg/m3. In a single 4-h exposure study at the maximum tested
      concentration of 7620 mg/m3, 1 of 10 female rats succumbed (no mortality in
      males), while no mortality occurred at 3293 mg/m3. In the 1- and 4-wk studies
      mortality occurred at 1283.7 and 702.3 mg/m3, respectively. Rats exposed for 4 wk
      to 702.3 mg/m3 displayed characteristic signs of toxicity that included cyanosis,
      respiratory distress, and significantly decreased body weights. Rectal
      temperatures were significantly decreased at 115.1 mg/m3 and above. Dark and
      enlarged spleens occurred at 702.3 mg/m3. At this concentration, prominent
      treatment-related effects included methemoglobinemia, reticulocytosis, red blood
      cells with Heinz bodies, decreased hemoglobin, hematocrit, and red blood cell
      counts. Borderline evidence of erythrocytotoxicty was noticed at 115.1 mg/m3
      (based on a minimal increase in Heinz bodies). Spleen and liver weights were
      significantly increased at 702.3 mg/m3, whereas the thymus weight was decreased
      at 115.1 mg/m3 and above. Microscopic changes were found in the spleen
      (hemosiderosis) at 702.3 mg/m3. An atrophy of the olfactory epithelium in the
      nasal cavities occurred at 115.1 mg/m3 and above. Clinical pathology revealed
      changes pathognostic of hepatic effects, although microscopic examinations did
      not reveal any specific changes. The no-observed-adverse-effect level (NOAEL) of
      the 4-wk study was 19.1 mg/m3 and is based on the predominant atrophic changes of
      the olfactory epithelium and the minimal to borderline erythrocytotoxic effects
      at 115.1 mg/m3.

PMID- 17043031
TI  - Brevetoxin-induced neural insult in the retrosplenial cortex of mouse brain.
AB  - Brevetoxins (polyether breve toxins; PbTx) are polyether neurotoxins produced by
      the marine dinoflagellate Karenia brevis, an organism associated with red tide
      blooms in the Gulf of Mexico and along the Atlantic coast from Florida to North
      Carolina. Brevetoxin-3 (PbTx-3) is a major component of the array of brevetoxins
      found in marine aerosols measured along red tide affected beaches. Humans exposed
      to aerosolized brevetoxins for short periods of time often suffer a variety of
      adverse health effects. It was consequently of interest to assess the potential
      for aerosolized brevetoxin to produce a neurotoxic response. Female BALB/c mice
      were exposed nose-only for 2 consecutive days to PbTx-3 aerosol, with a 2-h
      exposure on the first day and a 4-h exposure on the second day. The average PbTx
      3 exposure concentrations on days 1 and 2 were 312 +/- 113 mug brevetoxin 3/m3
      and 278 +/- 24 mug brevetoxin 3/m3, respectively. The brevetoxin-containing
      aerosol had a mass median aerodynamic diameter of 0.92 mum with a geometric
      standard deviation of 1.38. Coronal sections of mouse brains were evaluated for
      neuronal damage using both silver and Fluoro-Jade B staining to identify
      degenerating neuronal elements. PbTx-3 inhalation exposure produced neuronal
      degeneration in the posterior cingulate/retrosplenial cortex of mice as evidenced
      by silver-positive degenerating neurons in this region. No staining was found in
      other regions of the PBTx-3-exposed mouse brains or in brains of control, sham
      exposed mice. The existence of a neurotoxic insult in PbTx-3-exposed mice was
      confirmed using Fluoro-Jade B to label degenerating neurons. Fluro-Jade-positive
      neurons were observed in the retrosplenial cortex of PBTx-3 exposed, but not
      control, mice. These results suggest that subacute exposure to PbTx-3 for 2 days
      is sufficient to induce neuronal degeneration in a discrete region of the mouse
      cerebral cortex.

PMID- 17043033
TI  - Sampling period determination for heart rate logging under an exercise regimen.
AB  - Using a mathematical procedure, we determine appropriate sampling rates for
      logging heart rate, at a variety of exercise intensities. The mathematical
      procedure involves correlating exercise and heart rate data to determine a
      dynamical mathematical model, from which the frequency response of the
      relationship between exercise intensity and heart rate can be determined. The
      sampling rate is then straightforwardly deduced by making appropriate
      measurements on the frequency response curve. We show how careful consideration
      needs to be given to the choice of dynamical model structure and the work
      regimen, so that consistent and convincing conclusions can be drawn. We
      demonstrate that the dynamics of the work-rate/heart-rate system are dependent on
      the nominal work/heart rate, but a 5-s sampling period, as used in many
      commercial heart rate monitors, appears to be adequate, especially when some
      averaging is performed before logging.

PMID- 17043034
TI  - Ecological validity of neuropsychological assessment and perceived employability.
AB  - Ecological validity studies that have examined the relationship between cognitive
      abilities and employment in psychiatric and medical populations have found that a
      wide range of cognitive domains predict employability, although memory and
      executive skills appear to be the most important. However, no information is
      available regarding a patient's self-perceived work attributes and objective
      neuropsychological performance, and whether the same cognitive domains associated
      with successful employment are also related to a patient's self-perception of
      work competence. In the present study, 73 medical and psychiatric patients
      underwent comprehensive neuropsychological assessment. Step-wise multiple
      regression analyses revealed that the visual-spatial domain was the only
      significant predictor of self-perceived work attributes and work competence as
      measured by the Working Inventory (WI) and the Work Adjustment Inventory (WAI),
      accounting for 7% to 10% of inventory score variability. The results raise the
      intriguing possibility that targeting of visual spatial skills for remediation
      and development might play a separate and unique role in the vocational
      rehabilitation of a lower SES population, specifically, by leading to enhanced
      self-perception of work competence as these individuals attempt to enter the job
      market.

PMID- 17043035
TI  - Idiopathic sudden hearing loss: contradictory clinical evidence, placebo effects
      and high spontaneous recovery rate--where do we stand in assessing treatment
      outcomes?
AB  - Idiopathic sudden hearing loss (ISHL) has an estimated incidence of 10-20/100,000
      per year, impairing not only patients' hearing but also their ability to interact
      socially and their quality of life. Confronted with patients who demand
      successful treatment, physicians need to judge potential treatment options with
      regard to their reported efficiency, as well as their suitability for the
      individual patient. The dilemma of assessing treatment outcomes and options in
      ISHL will be discussed regarding a lack of knowledge of the disease's etiology,
      contradictory clinical evidence, high spontaneous recovery rate, and possible
      placebo effects. In conclusion, there is a dearth of structured research adhering
      to a common protocol, which makes comparison of trials and assessment of
      potential treatment outcomes difficult. Further research is warranted, taking
      some key recommendations into consideration.

PMID- 17043037
TI  - Seasonal variation of falling asleep while driving: An examination of fatal road
      accidents.
AB  - Road accidents related to sleep show a clear time-of-day pattern. Following the
      previous finding that such accidents in Finland happen more often (absolutely and
      relatively) during the summer months, especially during the afternoon, the main
      aim of this study was to reveal the factors behind such seasonality. The data
      included the computerized database of the Finnish fatal road accident
      investigation system restricted to nonprofessional, non-intoxicated car drivers
      (N=1464) and sample of the original folders (N=101). The results of the analysis
      on the sample of the original folders showed that investigation teams adequately
      documented and explained their decisions concerning falling-asleep accidents and
      that the observed seasonality is a real phenomenon, not a result of bias of the
      teams. With the exception of 26-35-year-olds, men of all of the other age groups
      had a notable absolute and relative increase of sleep-related accidents in the
      summer. Young male drivers (< or =25 yrs), followed by the oldest group (> or =66
      yrs) had the highest increase in the absolute number of sleep-related accidents
      between the summer and winter months, while the relative change was the highest
      for ages 56-65. Women showed similar trends. A detailed analysis of 44 cases of
      summer afternoon falling-asleep accidents revealed that many drivers were engaged
      in unusual activities the day or night before the accident. The findings are
      discussed in relation to different driving and lifestyle habits between seasons,
      including sleep quality. Preliminary results of this study were presented at the
      17th Congress of the European Sleep Research Society, Prague 2004.

PMID- 17043038
TI  - Cross-sectional reference values for height, weight and body mass index of school
      children living in Tehran, Iran.
AB  - AIM: The aim of the study was to create reference values for weight, height and
      body mass index (BMI) of school children living in Tehran. METHOD AND SAMPLES:
      The study subjects consisted of 1,420 girls between 6 and 17 years of age and
      1,515 boys between 6 and 15 years of age. Samples were collected by a multistage
      sampling method from schools in different areas of Tehran. All participants were
      established to be healthy and their height, weight and BMI evaluated. Reference
      standard values estimated by the LMS method using LMS Light software and 3rd,
      5th, 10th, 25th, 50th, 75th, 90th, 97th and 85th (only for BMI) centiles were
      constructed and the results compared with US reference values. RESULTS: The
      centiles provided a good fit to the data. In boys, there were some significant
      differences of mean standard deviation scores (SDS) of height and BMI from zero,
      but there were no significant differences in weight. In girls, the mean SDS of
      height, weight and BMI were significantly lower than zero, especially for 7-9
      years of age. Among 12-13-year-old girls, the mean SDS of height, weight and BMI
      came closer to zero, and the differences were not significant. Thereafter,
      although girls seemed to be shorter than US reference measures, their weight and
      BMI did not differ from reference values significantly. CONCLUSION: Our results
      for boys between 6 and 15 years are comparable with US reference values; however,
      the US reference values, especially for height, are not applicable for Iranian
      girls between 6 and 17 years.

PMID- 17043039
TI  - Present and future biochemical markers for detection of acute coronary syndrome.
AB  - The use of biochemical markers in the diagnosis and management of patients with
      acute coronary syndrome has increased continually in recent decades. The
      development of highly sensitive and cardiac-specific troponin assays has changed
      the view on diagnosis of myocardial infarction and also extended the role of
      biochemical markers of necrosis into risk stratification and guidance for
      treatment. The consensus definition of myocardial infarction places increased
      emphasis on cardiac marker testing, with cardiac troponin replacing creatine
      kinase MB as the "gold standard" for diagnosis of myocardial infarction. Along
      with advances in the use of more cardiac-specific markers of myocardial necrosis,
      biochemical markers that are involved in the progression of atherosclerotic
      plaques to the vulnerable state or that signal the presence of vulnerable plaques
      have recently been identified. These markers have variable abilities to predict
      the risk of an individual for acute coronary syndrome. The aim of this review is
      to provide an overview of the well-established markers of myocardial necrosis,
      with a special focus on cardiac troponin I, together with a summary of some of
      the potential future markers of inflammation, plaque instability, and ischemia.

PMID- 17043040
TI  - Influence of particle size on drug delivery to rat alveolar macrophages following
      pulmonary administration of ciprofloxacin incorporated into liposomes.
AB  - In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into
      liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasite
      infections, the influence of particle size on drug delivery to rat alveolar
      macrophages (AMs) following pulmonary administration of CPFX-liposomes was
      investigated. CPFX-liposomes were prepared with hydrogenated soybean
      phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a
      lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five
      different particle sizes (100, 200, 400, 1000 and 2000 nm). In the
      pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following
      pulmonary administration of CPFX-liposomes increased with the increase in the
      particle size over the range 100-1000 nm and became constant at over 1000 nm. The
      concentrations of CPFX in rat AMs until 24 h after pulmonary administration of
      CPFX-liposomes with a particle size of 1000 nm were higher than the minimum
      inhibitory concentration of CPFX against various intracellular parasites. In a
      cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues
      by pulmonary administration of CPFX-liposomes with a particle size of 1000 nm was
      observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX
      liposomes with a particle size of 1000 nm induces an excellent antibacterial
      effect without any cytotoxic effects on lung tissues. Therefore, CPFX-liposomes
      may be useful in the development of drug delivery systems for the treatment of
      respiratory infections caused by intracellular parasites, such as Mycobacterium
      tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.

PMID- 17043042
TI  - Role of TNFRp55 in Yersinia enterocolitica O:3-induced arthritis: triggering
      bacterial antigens and articular immune response.
AB  - OBJECTIVES: The pathogenesis of reactive arthritis (ReA), an aseptic synovitis
      that follows an extra-articular infection, is incompletely known. We studied the
      impact of tumour necrosis factor receptor (TNFR) p55 deficiency on the
      progression to ReA after oral Yersinia enterocolitica O:3 infection, the Yersinia
      antigens triggering articular inflammation and a possible articular TNFRp55
      mediated mechanism that protects against ReA. METHODS: Wild-type C57BL/6 and
      TNFRp55-/- mice were orogastrically infected with Y. enterocolitica O:3 and
      monitored for survival and arthritis development. The bacterial load was
      determined in mesenteric lymph nodes (MLNs), the spleen and joints. Interferon
      (IFN)-gamma, TNF-alpha and IL-10 mRNA expression in MLN and joints were analysed
      by reverse transcription-polymerase chain reaction (RT-PCR). Articular antibodies
      to Yersinia antigens, TNF-alpha protein and nitric oxide (NO) levels were
      assessed. Acute arthritis was evaluated after joint injection of Yersinia
      antigens. RESULTS: The survival rate was 60% in TNFRp55-/- mice. They showed
      impaired bacterial clearance in MLN, the spleen and joints, and excessive mRNA
      expression of pro-inflammatory cytokines in MLN. Clinical and histological
      examinations revealed that TNFRp55-/- mice developed severe arthritis. Moreover,
      augmented articular outer membrane protein (OMP)-specific antibodies and TNF
      alpha but impaired NO levels were detected in TNFRp55-/- mice. Synovial
      inflammatory response was detected by joint OMP injection. CONCLUSIONS: TNFRp55
      mediated immune mechanisms prevent ReA development after oral infection with Y.
      enterocolitica O:3. Yersinia OMPs are the relevant antigens triggering ReA. NO
      induction through TNFRp55 signalling could have a local antibacterial function to
      prevent ReA. This study could contribute to ReA-specific therapeutic studies.

PMID- 17043043
TI  - Traditional cardiovascular risk factors in primary Sjogren's syndrome--role of
      dyslipidaemia.

PMID- 17043046
TI  - Patient perception of UK scleroderma services--results of an anonymous
      questionnaire.

PMID- 17043045
TI  - A longitudinal study exploring pain control, treatment and service provision for
      individuals with end-stage lower limb osteoarthritis.
AB  - OBJECTIVE: To investigate the level of pain control, treatment and service
      provision amongst individuals with end-stage lower limb osteoarthritis who were
      on the waiting list for hip or knee joint replacement. METHODS: A total of 105
      patients on a waiting list for primary knee or hip replacement from a regional
      orthopaedic centre in the UK were recruited. The study was longitudinal and based
      on direct interviews at baseline and 6 months, with a postal questionnaire at 3
      months. Data were collected on pain by a visual analogue scale (VAS) and the
      Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. In
      addition, medication and the use of services and treatments were recorded.
      RESULTS: Participants experienced high levels of pain as measured by VAS [mean
      7.0; 95% confidence interval (CI) 6.6-7.5] and WOMAC pain (mean 11.2; 95% CI 10.6
      11.9). The majority of participants (78, 74%) was taking analgesics more than
      once a day. Primary care utilization was variable. Of the 74 (70%) participants
      who had consulted their GP in the previous 3 months, 41 (55%) had not discussed
      their pain or osteoarthritis during these consultations. Just below one-third of
      participants (31, 30%) reported to have received information on osteoarthritis.
      CONCLUSIONS: Pain appears to be difficult to manage in individuals with end-stage
      lower limb osteoarthritis. Individuals appeared not to be taking appropriate
      levels of analgesia in relation to levels of pain. Improvements are required in
      the provision of information on pain and osteoarthritis. Patients would benefit
      from more proactive management by health professionals (especially by GPs).

PMID- 17043047
TI  - Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis.
AB  - OBJECTIVES: Extracellular inorganic pyrophosphate (ePPi) inhibits certain forms
      of pathological mineralization while promoting others. Three molecules involved
      in ePPi regulation are important candidates for the development of calcium
      pyrophosphate dihydrate chondrocalcinosis (CPPD CC). These include ANKH,
      ectonucleotide pyrophosphatase (ENPP1) and TNAP. We have previously showed that
      genetic variation in ANKH is a cause of autosomal dominant familial CC and also
      some sporadic cases of CPPD CC. We now investigate the possible role of ENPP1 and
      TNAP in CPPD CC. METHODS: Exons, untranslated regions (UTR) and exon-intron
      boundaries of ENPP1 and TNAP were sequenced using ABI Big Dye chemistry on
      automated sequencers. Sixteen variants were identified (3 in ENPP1 and 13 in
      TNAP) and were subsequently genotyped in 128 sporadic Caucasian CPPD CC patients
      and 600 healthy controls using a combination of polymerase chain
      reaction/restriction fragment-length polymorphism analysis or using Taqman.
      Allele and genotype frequencies were compared between cases and controls using
      the chi(2) test. Linkage disequilibrium, haplotype and the single nucleotide
      polymorphism-specific analyses were also performed. This study had 80% power to
      detect an odds ratio of 2.2 or more at these loci. RESULTS: No difference was
      observed in the allele or genotype frequencies between patients and controls at
      either ENPP1 or TNAP. CONCLUSIONS: Polymorphisms of ENPP1 and TNAP are not major
      determinants of susceptibility to CC in the population studied. Further studies
      of the aetiology of sporadic CPPD CC are required to determine its causes.

PMID- 17043048
TI  - The differential expression of corticosteroid receptor isoforms in corticosteroid
      resistant and -sensitive patients with rheumatoid arthritis.
AB  - OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) fail to
      respond adequately to corticosteroid (CS) therapy. Using an in vitro CS
      sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS)
      and -resistant (SR) subgroups and this correlates with clinical responses to CS
      therapy. CSs exert their effects via the CS receptor (CR), which exists as two
      main isoforms, CRalpha and CRbeta. CRbeta can function as a negative inhibitor of
      CRalpha. We have hypothesized that steroid resistance in RA patients is due in
      part to a relative over-expression of the CRbeta. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CRalpha and
      CRbeta mRNA expression was determined by quantitative real time polymerase chain
      reaction (qRT-PCR). The ratio of CRbeta/CRalpha mRNA expression was determined.
      CRalpha and CRbeta protein expression by PBMCs was analysed by flow cytometry.
      RESULTS: qRT-PCR analysis showed a trend towards higher expression of both CRbeta
      and basal CRbeta/CRalpha ratio in SR RA patients. Stimulation of PBMCs in vitro
      with concanavalin-A induced a significantly higher CRbeta mRNA expression, and
      CRbeta/CRalpha ratio in SR RA patients compared with SS patients, which was not
      inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs
      staining for CRbeta protein was significantly lower in the SS RA group (SS 43.3
      +/- 14.8% vs SR 88.6 +/- 8.6%; P < 0.0010). The mean intensity of fluorescence
      CRbeta staining was higher in the SR RA patients (P < 0.001). CONCLUSION: We show
      for the first time that CRbeta is over-expressed in SR RA patients and that
      hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA
      in SR RA patients. This mechanism may contribute in part to the CS
      hyporesponsiveness seen in some RA patients.

PMID- 17043049
TI  - Very early 'Rheumatoid' arthritis cohorts: limited by selection.

PMID- 17043050
TI  - Engagement and satisfaction with an Internet-based physical activity intervention
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the engagement in and satisfaction with an Internet-mediated
      physical activity intervention with individual supervision in patients with
      rheumatoid arthritis (RA). METHODS: The intervention studied was one of the two
      strategies aimed at enhancing physical activity in RA patients that were being
      compared in a randomized controlled trial. A total of 82 patients, all
      experienced in using Internet and e-mail and registered at three different
      rheumatology out-patient clinics, were randomly allocated to the Internet
      mediated individualized intervention (52 weeks). They had access to personal
      physical activity schedules and received individual supervision by a physical
      therapist by means of weekly e-mail feedback. In addition, telephone contacts, an
      online discussion forum, six face-to-face group meetings and electronic
      newsletters were offered. Besides registration of returned physical activity
      schedules, engagement and satisfaction were measured through questionnaires.
      RESULTS: The median physical activity schedule return rate of the 82 participants
      was 55%. The mean number of patients logging into the website at least once a
      week was 53 (70%) over 12 months. Of all patients, 69 returned the questionnaires
      (response 84%). Telephone contacts were used by 38/67 patients (57%), the mean
      (SD) number of attended group meetings was 3.1 (1.5) and the discussion forum
      comprised 15 posted messages. Overall, the proportions of patients being (very)
      satisfied with the amount of e-mail contacts, telephone contacts, usefulness of
      website information, physical activity schedules, group meetings and website
      layout were >/=85%. A smaller proportion of patients were satisfied with the
      links to other websites (68%), the newsletters (55%) and the online discussion
      forum (32%). CONCLUSION: Physical activity schedules with weekly feedback by e
      mail, telephone contacts and a limited number of group meetings were frequently
      used website tools and modes of communication of an Internet-based physical
      activity intervention, with high-satisfaction rates from RA patients. Discussion
      forum and newsletters were less used and appreciated. Caution should be taken
      when extrapolating the results found to groups of patients who are not
      experienced Internet and e-mail users or patients with more severe physical
      disabilities.

PMID- 17043051
TI  - Invasive fungal infection in systemic lupus erythematosus: an analysis of 15
      cases and a literature review.
AB  - OBJECTIVE: To analyse 15 cases of invasive fungal infection and mortality
      parameters in the largest series in the last 35 yrs of patients with systemic
      lupus erythematosus (SLE) at a single medical centre. METHODS: Fifteen patients
      with SLE and invasive fungal infections were retrospectively enrolled. Clinical
      and laboratory data, fungal species and infected sites, corticosteroid and
      immunosuppressant doses and SLE disease activity index were assessed
      retrospectively. Comparison and correlation analyses utilized Fisher's exact
      test, the chi-square test, Mann-Whitney U-test or the Wilcoxon signed-rank test
      where appropriate. RESULTS: In contrast to other review reports, Cryptococcus
      neoformans was the most commonly identified fungus in this Taiwanese series.
      Notably, the prevalence of autoimmune haemolytic anaemia and positive results for
      the anti-cardiolipin antibody in this study were significantly higher than those
      in SLE patients in general (P < 0.0001 and P < 0.0001, respectively). Fungal
      infection contributed to cause of death in 7 of 15 (46.7%) patients, of which
      Cryptococcus neoformans accounted for six of these infections. Low-dose
      prednisolone (<1 or <0.5 mg/kg/day based on arbitrary division) prior to fungal
      infection tended to correlate with 1 yr mortality after diagnosis of SLE (P =
      0.077 or P = 0.080). However, following fungal infection, patients who died from
      infection itself had been prescribed with higher prednisolone dose or equivalent
      than surviving patients (P = 0.016). All SLE patients with fungal infections had
      active SLE (SLEDAI >7). CONCLUSIONS: Cryptococcus neoformans infection accounted
      for most fatalities in SLE patients with fungal infections in this series. Active
      lupus disease is probably a risk factor for fungal infection in SLE patients.
      Notably, low prednisolone doses prior to fungal infection or high prednisolone
      doses following fungal infection tended to associate with or correlated to
      fatality, respectively. Therefore, we suggest that different prednisolone doses
      prescribed at various times impact the incidence of fungal infection and its
      associated mortality.

PMID- 17043052
TI  - Atorvastatine for chronic synovitis due to massive intra-articular cholesterol
      monohydrate deposition in long-standing rheumatoid arthritis.

PMID- 17043053
TI  - Takayasu's arteritis--recent advances in imaging offer promise.
AB  - Takayasu's arteritis (TA), a rare large vessel vasculitis of unknown aetiology,
      remains a difficult disease to manage with diagnosis often delayed until the late
      occlusive stage when irreversible vascular damage has occurred. Recent studies
      suggest that non-invasive imaging modalities including magnetic resonance
      imaging, ultrasound and 18F-fluorodeoxyglucose positron emission tomography (18F
      FDG-PET) allow diagnosis of TA earlier in the disease course than standard
      angiography and provide a means for monitoring disease activity. Choice of
      appropriate therapy for TA is limited by a lack of evidence and a combination of
      corticosteroids and immunosuppressive drugs is most commonly used. Novel
      therapeutic approaches such as the use of anti-tumour necrosis factor alpha (TNF
      alpha) inhibitors and drug-eluting arterial stents show promise for improving the
      prognosis in severe disease. In addition, strict management of traditional
      cardiovascular risk factors such as dyslipidaemia, hypertension and lifestyle
      factors is mandatory to minimize secondary cardiovascular complications, which
      are the major cause of death in this disease.

PMID- 17043054
TI  - Mass spectrometric mapping of linker histone H1 variants reveals multiple
      acetylations, methylations, and phosphorylation as well as differences between
      cell culture and tissue.
AB  - Posttranslational modifications of histones are involved in regulation of
      chromatin structure and gene activity. Whereas the modifications of the core
      histones H2A, H2B, H3, and H4 have been extensively studied, our knowledge of H1
      modifications remained mainly limited to its phosphorylation. Here we analyzed
      the composition of histone H1 variants and their modifications in two human cell
      lines and nine mouse tissues. Use of a hybrid linear ion trap-orbitrap mass
      spectrometer facilitated assignment of modifications by high resolution and low
      ppm mass accuracy for both the precursor and product mass spectra. Across
      different tissues we identified a range of phosphorylation, acetylation, and
      methylation sites. We also mapped sites of ubiquitination and report
      identification of formylated lysine residues. Interestingly many of the mapped
      modifications are located within the globular domain of the histones at sites
      that are thought to be involved in binding to nucleosomal DNA. Investigation of
      mouse tissue in addition to cell lines uncovered a number of interesting
      differences. For example, whereas methylation sites are frequent in tissues, this
      type of modification was much less abundant in cultured cells and escaped
      detection. Our study significantly extends the known spectrum of linker histone
      variability.

PMID- 17043055
TI  - The results of cosmic radiation in-flight TEPC measurements during the CAATER
      flight campaign and comparison with simulation.
AB  - The European-Commission-supported project DOSMAX (Dosimetry of Aircrew Exposure
      to Radiation During Solar Maximum) was aimed at measuring aircrew exposure to
      cosmic radiation on-board the aircraft during solar maximum. During a dedicated
      international comparison mission (Co-ordinated Access to Aircraft for
      Transnational Environmental Research; CAATER) different measurement techniques
      have been compared by six European institutes (Results of the CAATER Mission,
      DOSMAX Meeting, Dublin, June 2004). In this paper, we present the tissue
      equivalent proportional counter (TEPC) measurements carried out by ARC
      Seibersdorf research (ARCS), Austria, and Institut de Radioprotection et de
      Surete Nucleaire (IRSN), France, together with a comparison with simulation
      results under the same conditions. The whole flight campaign consists of four
      different in-flight investigations performed at two different geographical
      positions at 12.2 km (FL 400) and 9.8 km (FL 320). One location was chosen above
      Rome (42 degrees North, 12 degrees East), Italy, for high cut-off rigidity (6.4
      GV) and the second above Aalborg (57 degrees North, 10 degrees East), Denmark,
      for low cut-off rigidity (1.8 GV). The TEPC measurements are presented in terms
      of absorbed dose and ambient dose equivalent as well as microdosimetric spectra
      as a function of lineal energy. For the same conditions of the CAATER flights the
      response of the TEPC has also been simulated by using the Monte Carlo Transport
      Code FLUKA (version 2003). The results from simulations are compared with
      measurements and they show a reasonable agreement.

PMID- 17043056
TI  - Negative selection with the Diphtheria toxin A fragment gene improves frequency
      of Cre-mediated cassette exchange in ES cells.
AB  - The Cre-lox system is an important tool for genetic manipulation in embryonic
      stem cells. We previously reported that the cassette exchange strategy using the
      mutant lox66/71 and lox2272 combination showed high recombination efficiency and
      stability. However, the efficiency was strongly affected by the position of
      chromosomal target lox sites. To enrich successful cassette exchange events, even
      in clones showing lower recombination efficiency, we have improved exchange
      vector. The Diphtheria toxin A fragment gene was placed in the un-exchanged
      region for negative selection and the puromycin N-acetyltransferase gene, instead
      of the neomycin phosphotransferase gene, was used for positive selection. By
      reducing random integration, the frequency of successful cassette exchange
      increased up to 2-4 fold. Furthermore, by adding the third lox site to induce
      intrarmolecular recombination, the recombination efficiency of cassette exchange
      itself was improved, and the frequency increased to maximum 5 fold, in which the
      percentage of exchanged clones reached to 50-70%. This strategy should be useful
      for other recombinase-mediated cassette exchanges.

PMID- 17043057
TI  - PTEN c.511C>T nonsense mutation in a BRRS family disrupts a potential exonic
      splicing enhancer and causes exon skipping.
AB  - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is an autosomal dominant disorder
      characterized by macrocephaly, intestinal hamartomatous polyps, lipomas and
      pigmented macules of the glans penis. We identified a Thai family affected with
      BRRS. In addition to typical manifestations of BRRS, the proband has a large
      hepatic AVM which is rarely found in BRRS. The molecular analysis revealed
      affected members were heterozygous for an exon skipping-associated nonsense
      mutation c.511C>T in the PTEN gene. The mutation was previously assumed to be
      deleterious by causing a change to a termination codon, Q171X. We, herein, found
      that another pathogenic effect was splicing related by disrupting a potential
      exonic splicing enhancer (ESE) and causing an entire exon 6 skipping. The results
      prompted us to investigate other reported missense/nonsense mutations in the PTEN
      gene. We found that they do not colocalize with ESE sites, suggesting that most
      of their pathogenic effects are not through ESE disruption.

PMID- 17043058
TI  - The range of tumor extension should have precedence over the location of the
      deepest tumor center in determining the regional lymph node grouping for widely
      extending esophageal carcinomas.
AB  - BACKGROUND: The Japanese Guide Lines for the Clinical and Pathologic Studies on
      Carcinoma of the Esophagus (9th edn) give precedence to the location of the
      deepest tumor center rather than the range of tumor extension when determining
      regional lymph node grouping. We evaluated the validity of this recommendation.
      METHODS: The subjects were 49 patients with carcinomas of the distal thoracic
      esophagus and cardia who had undergone esophagectomy with three-field lymph node
      dissection. We measured variables defining tumor location, such as the distance
      from the esophagogastric junction (EGJ) to the proximal margin of the tumor
      (DJP), the distance from the EGJ to the distal margin of the tumor (DJD), and the
      distance from the EGJ to the deepest tumor center (DJC). To examine the relation
      of tumor location to lymph node metastasis in the proximal direction, the
      patients were divided into two groups according to the presence (14 patients) or
      absence (35 patients) of middle-upper mediastinal and/or cervical lymph node
      metastases. These two groups were compared with respect to the above variables.
      To analyze lymph node metastasis in the distal direction, the patients were also
      divided into two groups according to the presence (12 patients) or absence (37
      patients) of distant abdominal lymph node metastases. These two groups were
      similarly compared with respect to the above variables. RESULTS: DJP was
      significantly longer in the patients with middle-upper mediastinal and/or
      cervical lymph node metastases than in those without such metastases. Multiple
      logistic regression analysis showed that the DJP was a better predictor of middle
      upper mediastinal and/or cervical lymph node metastases than was the DJC. The DJD
      was significantly longer in the patients with distant abdominal lymph node
      metastases. Multiple logistic regression analysis also showed that the DJD was a
      better predictor of distant abdominal lymph node metastases than was the DJC.
      CONCLUSIONS: The range of tumor extension is a more reliable predictor of the
      risk of distant lymph node metastases than is the location of the deepest tumor
      center in esophageal carcinoma.

PMID- 17043059
TI  - A phase II trial of docetaxel plus capecitabine in patients with previously
      treated non-small cell lung cancer.
AB  - BACKGROUND: A combination of docetaxel (T) and capecitabine (X) showed
      synergistic effects in preclinical studies and phase III randomized trials of
      metastatic breast cancer. We conducted this phase II study to examine its
      efficacy in previously treated non-small cell lung cancer (NSCLC) patients.
      METHODS: Patient eligibility required advanced NSCLC with measurable lesion(s),
      at least one prior regimen failure and Eastern Cooperative Oncology Group (ECOG)
      performance status 0-2. Treatment consisted of T 36 mg/m(2) i.v. on days 1 and 8
      plus X 1000 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level I) or T 30
      mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21
      day cycle (level II). RESULTS: A total of 35 patients (M/F=24/11) were enrolled;
      29 had received one prior regimen and 19 had received platinum-based regimens.
      Significant non-hematologic toxicities were observed after the treatment given at
      level I, including one treatment-related death. Subsequently 29 patients were
      treated at level II. The treatment at level II was well tolerated with grade 3 or
      4 neutropenia only in 10%, grade 3 asthenia in 21% and stomatitis in 14% of
      patients. Four (15%) of 27 evaluable patients had partial response (PR) at level
      II and eight (30%) had stable disease (SD). CONCLUSIONS: The TX regimen showed
      modest antitumor effects in patients with previously treated NSCLC. For further
      studies, we recommend T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o.
      b.i.d. on days 1-14 of a 21-day cycle.

PMID- 17043060
TI  - Effect of clopidogrel on 1-year mortality in hospital survivors of acute ST
      segment elevation myocardial infarction in clinical practice.
AB  - AIMS: We sought to assess the effect of clopidogrel on clinical events 1 year
      after discharge in survivors of ST-elevation myocardial infarction (STEMI) in
      clinical practice. METHODS AND RESULTS: We analysed data of consecutive survivors
      of acute STEMI and either concomitant therapy with aspirin or aspirin plus
      clopidogrel at discharge, who were prospectively enrolled in the Acute Coronary
      Syndromes (ACOS) registry between July 2000 and November 2002. A total of 5886
      (3795 with and 2091 without clopidogrel) patients were included into this
      analysis. Patients were divided into three groups according to the initial
      reperfusion therapy: no reperfusion therapy (n=1445), fibrinolysis (n=1734), or
      primary PCI (n=2707). The multivariable analysis for 12+2 month mortality after
      discharge using the propenstiy score with adjustment for baseline characteristics
      and treatments (age, sex, diabetes mellitus, hypertension, prior MI,
      hyperlipidaemia, renal insufficiency, cardiogenic shock, heart rate, systolic
      blood pressure, anterior infarct location, reduced left ventricular function,
      elective revascularization, beta-blockers, statins, ACE-inhibitors) showed that
      mortality was significantly lower in the aspirin plus clopidogrel group compared
      with the aspirin group in the total group and patients with reperfusion therapy
      [total group odds ratio (OR) 0.48, 95% confidence interval (CI) 0.48-0.61; no
      reperfusion therapy OR 0.96, 95% CI 0.65-1.45; fibrinolysis OR 0.53, 95% CI 0.32
      0.87; primary percutaneous coronary intervention OR 0.38, 95% CI 0.23-0.62].
      CONCLUSION: In clinical practice, adjunctive therapy with clopidogrel, in
      addition to aspirin, in survivors after STEMI is associated with a reduction in 1
      year mortality in patients treated with early reperfusion therapy.

PMID- 17043061
TI  - Soccer world championship: a challenge for the cardiologist.
AB  - The 18th FIFA Soccer World Cup 2006 in Germany enthused millions of people
      worldwide, but only little is known about the association of such an event with
      cardiovascular events. Modest physical activity is known to reduce the
      cardiovascular risk significantly. On the other hand, vigorous physical activity
      and emotional strain increase the cardiovascular risk and the incidence of
      cardiovascular events likely due to an increased sympathetic tone with
      consecutive catecholamine stimulation of the heart. Few reviews and case-reports
      are dealing with the risk of physical activity in cardiovascular high-risk
      patients or athletes with congenital heart diseases (e.g. hypertrophic
      obstructive cardiomyopathy), but the impact of highly competitive events on
      cardiovascular events, especially in spectators were rarely addressed. Thus, the
      increased risk of cardiovascular events in players and spectators were addressed
      in this review with respect to various soccer matches and tournaments, such as
      the FIFA World Cup.

PMID- 17043062
TI  - 'Cobra malformation' of an Amplatzer device during percutaneous closure of a
      ventricular septal defect.

PMID- 17043063
TI  - Gigantic left atrial thrombus.

PMID- 17043064
TI  - Functional mitral regurgitation in acute coronary syndrome: what determines its
      prognostic impact?

PMID- 17043065
TI  - Australian parents' views on their 5-6-year-old children's food choices.
AB  - The home food environment is central to the development of healthy eating
      behaviours, but associations between the home food environment and children's
      food choices are not yet fully understood. The aims of this study were to explore
      parents' views regarding factors that influence children's food choices and
      parents' decision-making regarding the food they provide to their children. In
      depth one-on-one interviews were conducted using a semi-structured interview
      schedule. Key concepts and themes were coded independently by two investigators.
      Participants include seventeen parents (16 mothers and 1 father) of children in
      their first year of formal schooling (aged 5-6 years). Five main themes emerged
      from the interviews: food marketing, food availability/food exposure, feeding
      strategies, modelling of eating and opportunities for food involvement. Parents
      believed that food marketing influenced their child's food preferences but
      differed in the ways they managed these influences. The food made available to
      children was also seen to influence what a child ate. Yet, although some parents
      believed it was the parents' role to determine what foods were made available to
      their child, others offered food on the basis of the child's tastes or
      preferences. The use of food as a reward was a feeding strategy employed by many
      parents. Family mealtimes were seen as an important opportunity for modelling of
      eating behaviour by parents. Peers were also seen to influence children's food
      preferences and eating behaviour. Finally, many parents believed that involving
      children in the preparation of food had a positive impact on children's food
      choices. Associations between the home food environment and children's food
      choices are complex and involve multiple mediators. Parents' views on the
      promoters and reinforcers of their decision-making regarding food and their
      child's food choices provide useful insights into these mediating factors.
      Increased understanding of these relationships is likely to enhance obesity
      prevention efforts.

PMID- 17043066
TI  - P-selectin mediates metastatic progression through binding to sulfatides on tumor
      cells.
AB  - Hematogenous carcinoma metastasis is associated with tumor cell emboli formation,
      which is now known to be facilitated by selectins. P-selectin-mediated
      interactions of platelets with cancer cells are based mostly on mucin- and
      glycosaminoglycan-type selectin ligands. We previously showed that mouse colon
      carcinoma cells (MC-38) carry P-selectin ligands of nonmucin origin, which were
      not identified. Here we show that P-selectin ligands recognized on MC-38 cells
      are sulfated glycolipids, thereby facilitating experimental metastasis in a
      syngeneic mouse model. Metabolic inhibition of sulfation by incubation of cells
      with sodium chlorate almost completely abrogated P-selectin binding. Metabolic
      labeling of MC-38 cells with (35)S sulfate revealed only a single band as
      detected by high-performance thin layer chromatography analysis of a total lipid
      extract. Matrix-assisted laser desorption/ionization tandem time-of-flight/time
      of-flight analysis (MALDI-TOF-TOF) analysis of the purified sulfate-containing
      lipid fraction identified the selectin ligand to be a sulfated galactosylceramide
      SM4 (HSO(3)-3Galbeta-1Cer). Modulation of glycolipid biosynthesis in MC-38 cells
      altered P-selectin binding, thereby confirming sulfoglycolipids to be major P
      selectin ligands. In addition, P-selectin was also found to recognize
      lactosylceramide sulfate SM3 (HSO(3)-3Galbeta-4Glcbeta-1Cer) and
      gangliotriaosylceramide sulfate SM2 [GalNAcbeta-4(HSO(3)-3)Galbeta-4Glcbeta-1Cer]
      in human hepatoma cells. Finally, the enzymatic removal of sulfation from the
      cell surface of MC-38 cells resulted in decreased P-selectin binding and led to
      attenuation of metastasis. Thus, SM4 sulfatide serves as a native ligand for P
      selectin contributing to cell-cell interactions and to facilitation of
      metastasis.

PMID- 17043067
TI  - Analysis of surface electrocardiograms in atrial fibrillation: techniques,
      research, and clinical applications.
AB  - Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical
      practice. Neither the natural history of AF nor its response to therapy is
      sufficiently predictable by clinical and echocardiographic parameters. The
      purpose of this article is to describe technical aspects of novel
      electrocardiogram (ECG) analysis techniques and to present research and clinical
      applications of these methods for characterization of both the fibrillatory
      process and the ventricular response during AF. Atrial fibrillatory frequency (or
      rate) can reliably be assessed from the surface ECG using digital signal
      processing (extraction of atrial signals and spectral analysis). This measurement
      shows large inter-individual variability and correlates well with intra-atrial
      cycle length, a parameter which appears to have primary importance in AF
      maintenance and response to therapy. AF with a low fibrillatory rate is more
      likely to terminate spontaneously and responds better to antiarrhythmic drugs or
      cardioversion, whereas high-rate AF is more often persistent and refractory to
      therapy. Ventricular responses during AF can be characterized by a variety of
      methods, which include analysis of heart rate variability, RR-interval
      histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a
      certain degree of usefulness, either in scientific explorations of
      atrioventricular (AV) nodal function or in selected clinical questions such as
      predicting response to drugs, cardioversion, or AV nodal modification. The role
      of the autonomic nervous system for AF sustenance and termination, as well as for
      ventricular rate responses, can be explored by different ECG analysis methods. In
      conclusion, non-invasive characterization of atrial fibrillatory activity and
      ventricular response can be performed from the surface ECG in AF patients.
      Different signal processing techniques have been suggested for identification of
      underlying AF pathomechanisms and prediction of therapy efficacy.

PMID- 17043068
TI  - The assessment of autonomic function in chronic atrial fibrillation: description
      of a non-invasive technique based on circadian rhythm of atrioventricular nodal
      functional refractory periods.
AB  - AIMS: Heart rate variability (HRV) parameters can be used to assess autonomic
      function and to predict outcome, but this has been done exclusively in patients
      with sinus rhythm. Atrial fibrillation (AF) is the commonest sustained arrhythmia
      and is particularly prevalent in heart failure. We have developed a simple index
      to assess autonomic function in patients with chronic AF. METHODS AND RESULTS:
      Forty patients with chronic AF (>1 month) and symptoms of heart failure underwent
      ambulatory 24 h electrocardiography recording as well as evaluation of symptoms,
      exercise capacity (6 min walk distance), ventricular function (echocardiography
      and radionuclide ventriculography), and neuroendocrine activation. A number of
      standard HRV parameters shown to have prognostic significance in sinus rhythm
      were also determined. A modified in-house HRV statistical programme was used to
      filter labelled QRS intervals and to compute the 5th percentile RR interval in
      each hour. This parameter has been shown to approximate the functional refractory
      period (FRP) of the atrioventricular node (AVN). A cosine curve was fitted to
      hourly 5th percentile RR intervals for each patient and from this was estimated
      the diurnal change in hourly 5th percentile RR interval (approximating DeltaFRP
      of the AVN) and, by inference, diurnal variation in sympathovagal input to the
      AVN. Digoxin was the sole agent permitted for control of ventricular rate.
      DeltaFRP of the AVN varied and revealed a significant correlation, on
      multivariate analysis, with mean RR interval (P<0.001), SDARR (SD of 5-min
      average RR intervals during 24 h, P<0.001), and NYHA class of heart failure
      (classes III and IV heart failure vs. classes I and II, P=0.02). SDARR has
      previously been shown independently to predict mortality in patients with chronic
      AF and heart failure. CONCLUSION: This analysis describes a novel non-invasive
      method for assessing autonomic function in chronic AF. Whether DeltaFRP in
      chronic AF patients can independently predict adverse prognosis or sudden death
      requires further study.

PMID- 17043069
TI  - Verification of pacemaker automatic mode switching for the detection of atrial
      fibrillation and atrial tachycardia with Holter recording.
AB  - AIMS: Verification of the accuracy of onset, offset, and duration of automatic
      mode switching (AMS) of pacemakers compared with onset and end of atrial
      fibrillation (AF) or atrial tachycardia (AT). Correct pacemaker diagnosis of
      atrial tachyarrhythmias (AA) is indispensable for reliable automatic prevention
      and intervention algorithms of AA. METHODS AND RESULTS: Comparison was made of
      the AMS registration of the pacemaker-stored electrograms (EGMs) and the number
      and cumulative duration of these episodes with continuous 7-day Holter
      monitoring. Atrial sensitivity was kept at 0.5 mV and far field R-wave
      recognition in the atrial channel was excluded by blanking of this signal. Lead
      types were confined to leads with short-ring tip spacing (10-13.8 mm). During
      Holter monitoring, 18 of 57 included patients with standard reason for pacemaker
      implantation showed episodes of AF or AT. Cumulative duration of AF and AT from
      Holter was correctly interpreted by the pacemaker in 99.9% of the patients. All
      episodes of AF, as seen on the Holter recording, were recognized by the pacemaker
      (correlation 99.9%). During AF, multiple episodes of undersensing were detected.
      The number of AMS episodes was influenced by undersensing during AF. The
      influence of these short episodes of undersensing on the total duration of AF was
      trivial (cumulative duration of AF was 99.9% correct). In patients with AT
      without AF on Holter (n=7) and in contrast to the AF episodes, the cumulative AT
      duration did not correlate well (63%) with the Holter recordings. The number of
      AMS episodes in the setting of AT was influenced by the atrial tachycardia
      detection rate setting and the duration of the post-ventricular atrial blanking
      interval. CONCLUSION: The total duration of AF is correctly represented by the
      total duration of AMS and can be considered a reliable measure of total AF
      duration. AT duration was poorly correlated with AMS duration. The number of mode
      switches does not reflect the number of episodes of AF/AT. Increased memory
      capacity allowing the storing of all EGMs triggered by the initiation of AF/AT
      would be the ideal setting with which to optimize the diagnostic performance of
      pacemakers.

PMID- 17043070
TI  - The effectiveness of a high output/short duration radiofrequency current
      application technique in segmental pulmonary vein isolation for atrial
      fibrillation.
AB  - AIMS: Segmental pulmonary vein (PV) isolation by radiofrequency (RF) catheter
      ablation has become a curative therapy for atrial fibrillation (AF). However, the
      long procedure time limits the wide application of this procedure. The aim of the
      current study was to compare a novel ablation technique with a high power output
      and short application time vs. a conventional technique using a low power output
      and long application time. METHODS AND RESULTS: The study included 90 consecutive
      patients (age 53+/-10 years; 66 men). Segmental PV isolation was performed by
      irrigated RF catheter ablation in both groups. In the conventional group (Group
      1, 45 patients), the power output was limited to 30 W with a target temperature
      of 50 degrees C and an RF preset duration of 120 s. In the novel group (Group 2,
      45 patients), the maximum power output was preset to 45 W, with a target
      temperature of 55 degrees C and duration of 20 s. In Group 2, a significant
      reduction in the PV isolation time (127+/-57 vs. 94+/-33 min, P<0.02), mean
      fluoroscopy time (73+/-23 vs. 55+/-16 min, P<0.001), and radiation dose was
      observed. According to the application time and number, Group 2 showed a
      reduction in RF application time, but a higher number of RF applications were
      required for creation of complete PV isolation. During a mean follow-up of 15+/-7
      months, a total of 74% of patients in Group 1 and 76% of patients in Group 2
      demonstrated stable SR. CONCLUSION: Segmental PV isolation using a high power
      output and short application time is safe and effective in PV isolation in
      patients with AF. This technique can significantly reduce the procedure and
      fluoroscopy time compared with a low-power output technique.

PMID- 17043071
TI  - Substrate mapping vs. tachycardia mapping using CARTO in patients with coronary
      artery disease and ventricular tachycardia: impact on outcome of catheter
      ablation.
AB  - AIMS: For ablation of ventricular tachycardia (VT) in patients after myocardial
      infarction, a three-dimensional mapping system is often used. We report on our
      overall success rate of VT ablation using CARTO in 47 patients, with a subgroup
      analysis comparing VT mapping with the results of mapping that had to be
      performed during sinus rhythm or pacing (substrate mapping). METHODS AND RESULTS:
      A CARTO map was performed and VT ablation attempted using two strategies:
      Patients in the VT-mapping group had incessant VT (four patients) or inducible
      stable VT (18 patients) such that the circuit of the clinical VT could be
      reconstructed using CARTO. During VT, the critical area of slow conduction was
      identified using diastolic potentials and conventional concealed entrainment
      pacing. In contrast, patients in the substrate-mapping group had initially
      inducible VT. However, a complete VT map was not possible because of catheter
      induced mechanical block (six patients) or because haemodynamics deteriorated
      during the ongoing VT (19 patients). Therefore, pathological myocardium was
      identified by fragmented, late- and/or low-amplitude (<1.5 mV) bipolar potentials
      during sinus rhythm or pacing, and the ablation site was primarily determined by
      pace mapping inside or at the border of this pathological myocardium. Acute
      ablation success in all patients with regard to non-inducibility of the clinical
      VT or any slower VT was 79% after a single ablation procedure, but increased to
      95% after a mean of 1.2 ablation procedures. However, chronic success was 75%,
      when it was defined as freedom from any ventricular tachyarrhythmia (VT or VF)
      during a follow-up of 25+/-13 months. In the subgroup analysis, patients in the
      VT-mapping group were not significantly different from patients in the substrate
      mapping group with regard to age (65+/-7 vs. 65+/-9 years), ejection fraction
      (30+/-7 vs. 30+/-8%), VT cycle length (448+/-81 vs. 429+/-82 ms), number of
      radiofrequency applications (17+/-9 vs. 14+/-6 applications), use of an irrigated
      tip catheter (23 vs. 32%), and ablation results. CONCLUSION: When using a CARTO
      guided approach for VT ablation in patients with coronary artery disease, the
      freedom from any ventricular arrhythmia is high (75%), but leaves the patient at
      a 23% risk of developing fast VT/VF during follow-up. Mapping during sinus rhythm
      or pacing is as successful as mapping during VT.

PMID- 17043072
TI  - Cardiac pacing in sleep apnoea: diagnostic and therapeutic implications.
AB  - The sleep apnoea syndrome is a particularly common health problem associated with
      increased cardiovascular morbidity and mortality, as well as harmful
      socioeconomical and familial complications. In this article, the diagnostic and
      therapeutic role of cardiac pacing in this syndrome is discussed.

PMID- 17043073
TI  - Impact of left ventricular epicardial and biventricular pacing on ventricular
      repolarization in normal-heart individuals and patients with congestive heart
      failure.
AB  - AIMS: Malignant ventricular arrhythmias can arise in a subset of congestive heart
      failure (CHF) patients after they undergo cardiac resynchronization therapy
      (CRT), thus counteracting the haemodynamic benefits typically associated with
      biventricular pacing. This study seeks to assess whether alteration of the
      ventricular transmural repolarization and conduction due to reversal of the
      depolarization sequence during epicardial or biventricular pacing facilitate the
      development of ventricular arrhythmias. METHODS AND RESULTS: ECGs and monophasic
      action potential (MAP) were recorded during programmed stimulation from right
      ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or
      both (biventricular, Bi-V) in 15 individuals without structural heart diseases.
      In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo,
      LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT,
      and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and
      compared. In subjects with or without structural heart disease, compared with RV
      Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms
      with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in
      CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV
      Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal
      heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with
      Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition
      to prolonged myocardial repolarization time and delayed endocardial activation.
      During follow-up, sudden death and arrhythmia storm occurred in two CHF patients
      after CRT. CONCLUSION: Epicardial and biventricular pacing prolong the time and
      increase the dispersion of myocardial repolarization and delay the transmural
      conduction. All of these should be considered as potential arrhythmogenic factors
      in CHF patients who receive CRT.

PMID- 17043074
TI  - Different working and living conditions and their associations with persistent
      neck/shoulder and/or low back disorders.
AB  - OBJECTIVES: To investigate whether different combinations of working and living
      conditions are associated with the risk for persistent neck/shoulder and/or low
      back disorders. The underlying purpose of this contextual approach was to
      identify target groups for primary/secondary prevention. METHODS: In a baseline
      study, 11 groups with different working and living conditions were identified by
      cluster analysis. In this study, these 11 groups were followed up by a postal
      questionnaire 5 years after baseline (response rate 82%, n = 1095). RESULTS: Five
      of the groups--the onerous human services job, the free agent, the family burden,
      the mentally stretched and the physically strained groups--had an increased risk
      for persistent disorders (OR 2.38-2.70). Four of these groups had rather sex
      specific working and living conditions. CONCLUSIONS: The results support the
      hypothesis that different combinations of working and living conditions may
      increase the risk for persistent neck/shoulder and/or low back disorders to
      different degrees. Sex-specific working and living conditions increased the risk
      for women as well as for men, irrespective of whether the conditions were
      specific to women or men.

PMID- 17043075
TI  - Exposure to carcinogens for defined job categories in Norway's offshore petroleum
      industry, 1970 to 2005.
AB  - OBJECTIVES: To identify and describe the exposure to selected known and suspected
      carcinogenic agents, mixtures and exposure circumstances for defined job
      categories in Norway's offshore petroleum industry from 1970 to 2005, in order to
      provide exposure information for a planned cohort study on cancer. METHODS:
      Background information on possible exposure was obtained through company visits,
      including interviewing key personnel (n = 83) and collecting monitoring reports
      (n = 118) and other relevant documents (n = 329). On the basis of a previous
      questionnaire administered to present and former offshore employees in 1998, 27
      job categories were defined. RESULTS: This study indicated possible exposure to
      18 known and suspected carcinogenic agents, mixtures or exposure circumstances.
      Monitoring reports were obtained on seven agents (benzene, mineral oil mist and
      vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres,
      formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal
      samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6
      ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing
      brake bands were used in drilling draw work in 1988. Personal samples of
      formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of
      products containing known and suspected carcinogens, exposure sources and
      processes were extracted from the collected documentation and the interviews of
      key personnel. CONCLUSIONS: This study described exposure to 18 known and
      suspected carcinogenic agents, mixtures and exposure circumstances for 27 job
      categories in Norway's offshore petroleum industry. For a planned cohort study on
      cancer, quantitative estimates of exposure to benzene, and mineral oil mist and
      vapour might be developed. For the other agents, information in the present study
      can be used for further assessment of exposure, for instance, by expert
      judgement. More systematic exposure surveillance is needed in this industry. For
      future studies, new monitoring programmes need to be implemented.

PMID- 17043076
TI  - Enhanced preventive programme at a beryllium oxide ceramics facility reduces
      beryllium sensitisation among new workers.
AB  - BACKGROUND: A 1998 survey at a beryllium oxide ceramics manufacturing facility
      found that 10% of workers hired in the previous 6 years had beryllium
      sensitisation as determined by the beryllium lymphocyte proliferation test
      (BeLPT). In response, the facility implemented an enhanced preventive programme
      to reduce sensitisation, including increased respiratory and dermal protection
      and particle migration control. AIM: To assess the programme's effectiveness in
      preventing sensitisation. METHODS: In 2000, the facility began testing newly
      hired workers for beryllium sensitisation with the BeLPT at time of hire and
      during employment. The sensitisation rate and prevalence for workers hired from
      2000 to 2004 were compared with that for workers hired from 1993 to 1998, who
      were tested in the 1998 survey. Facility environmental conditions for both time
      periods were evaluated. RESULTS: Newly hired workers in both cohorts worked for a
      mean of 16 months. Of the 97 workers hired from 2000 to 2004 with at least one
      employment BeLPT result, four had abnormal results at time of hire and one became
      sensitised during employment. Of the 69 workers hired from 1993 to 1998 and
      tested in 1998, six were found to be sensitised. The sensitisation rate for the
      2000-4 workers was 0.7-2.7/1000 person-months of employment, and that for the
      1993-8 workers was 5.6/1000 person-months, at least 2.1 (95% confidence interval
      (CI) 0.6 to 8.4) and up to 8.2 (95% CI 1.2 to 188.8) times higher than that for
      the 2000-4 workers. The sensitisation prevalence for the 2000-4 workers was 1%
      and that for the 1993-8 workers was 8.7%, 8.4 (95% CI 1.04 to 68.49) times higher
      than that for the 2000-4 workers. Airborne beryllium levels for production
      workers for the two time periods were similar. CONCLUSIONS: A comprehensive
      preventive programme reduced beryllium sensitisation in new workers during the
      first years of employment, despite airborne beryllium levels for production
      workers that were similar to pre-programme levels.

PMID- 17043077
TI  - Occupational exposure to low frequency magnetic fields and dementia: a case
      control study.
AB  - BACKGROUND: Several studies point to a potential aetiological relevance to
      dementia of exposure to low-frequency magnetic fields, but the evidence is
      inconclusive. OBJECTIVE: To further examine the relationship between low
      frequency magnetic fields and dementia. METHODS: From 23 general practices, 195
      patients with dementia were recruited. Of these, 108 had possible Alzheimer's
      disease, 59 had possible vascular dementia and 28 had secondary or unclassified
      dementia. A total of 229 controls were recruited: 122 population controls and 107
      ambulatory patients free from dementia. Data were gathered in a structured
      personal interview; in cases, the interview was administered to the next of kin.
      Exposure to low-frequency electromagnetic fields was assessed by expert rating.
      To identify occupations suspected to be associated with dementia, major
      occupations were a priori formed. Odds ratios were calculated using logistic
      regression, to control for age, region, sex, dementia in parents and smoking.
      RESULTS: Exposure to magnetic fields was not significantly associated with
      dementia; restriction of the analysis to cases with possible Alzheimer's disease
      or possible vascular dementia did not lead to statistically significant results.
      We found an increased risk of dementia in blue-collar occupations (electrical and
      electronics workers, metal workers, construction workers, food and beverage
      processors and labourers). CONCLUSIONS: Our study does not support a strong
      association between occupational exposure to low-frequency magnetic fields and
      dementia. Further studies should consider the relationship between blue-collar
      work and the late development of dementia.

PMID- 17043078
TI  - Multidisciplinary consensus on the terminology and classification of complaints
      of the arm, neck and/or shoulder.
AB  - BACKGROUND: There is no universally accepted way of labelling or defining upper
      extremity musculoskeletal disorders. A variety of names are used and many
      different classification systems have been introduced. OBJECTIVE: To agree on an
      "unambiguous language" concerning the terminology and classification that can be
      used by all relevant medical and paramedical disciplines in the Netherlands.
      METHODS: A Delphi consensus strategy was initiated. The outcomes of a
      multidisciplinary conference were used as a starting point. In total, 47 experts
      in the field of upper-extremity musculoskeletal disorders were delegated by 11
      medical and paramedical professional associations to form the expert panel for
      the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an
      analysis and a feedback report. RESULTS: After three Delphi rounds, consensus was
      achieved. The experts reported the consensus in a model. This so-called CANS
      model describes the term, definition and classification of complaints of arm,
      neck and/or shoulder (CANS) and helps professionals to classify patients
      unambiguously. CANS is defined as "musculoskeletal complaints of arm, neck and/or
      shoulder not caused by acute trauma or by any systemic disease". The experts
      classified 23 disorders as specific CANS, because they were judged as diagnosable
      disorders. All other complaints were called non-specific CANS. In addition, the
      experts defined "alert symptoms" on the top of the model. CONCLUSIONS: The use of
      the CANS model can increase accurate and meaningful communication among
      healthcare workers, and may also have a positive influence on the quality of
      scientific research, by enabling comparison of data of different studies.

PMID- 17043079
TI  - Leukocyte telomere length and cardiovascular disease in the cardiovascular health
      study.
AB  - The telomere length of replicating somatic cells is inversely correlated with age
      and has been reported to be associated cross-sectionally with cardiovascular
      disease (CVD). Leukocyte telomere length, as expressed by mean terminal
      restriction fragment (TRF) length, was measured in 419 randomly selected
      participants from the Cardiovascular Health Study, comprising a community
      dwelling cohort recruited in four US communities. The authors investigated
      associations between TRF length and selected measures of subclinical CVD/risk
      factors for CVD (data were collected at the 1992/1993 clinic visit) and incident
      CVD (ascertained through June 2002). In these participants (average age = 74.2
      years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs
      (standard deviation, 0.62). Significant or borderline inverse associations were
      found between TRF length and diabetes, glucose, insulin, diastolic blood
      pressure, carotid intima-media thickness, and interleukin-6. Associations with
      body size and C-reactive protein were modified by gender and age, occurring only
      in men and in participants aged 73 years or younger. In younger (but not older)
      participants, each shortened kilobase pair of TRF corresponded with a threefold
      increased risk of myocardial infarction (hazard ratio = 3.08, 95% confidence
      interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95% confidence interval:
      1.29, 8.02). These results support the hypotheses that telomere attrition may be
      related to diseases of aging through mechanisms involving oxidative stress,
      inflammation, and progression to CVD.

PMID- 17043080
TI  - Re: "when is baseline adjustment useful in analyses of change? An example with
      education and cognitive change".

PMID- 17043081
TI  - Tissue growth in a rotating bioreactor. Part II: fluid flow and nutrient
      transport problems.
AB  - Fluid flow and nutrient transport around a growing tissue construct within a
      cylindrical bioreactor of circular cross-section are considered. The bioreactor
      is filled with nutrient-rich culture medium, and the growing tissue construct is
      modelled as a cylindrical obstacle, also of circular cross-section, at a given
      (moving) position within the nutrient solution. The bioreactor rotates about its
      cylindrical axis, and its axial length is small relative to its radius (the high
      aspect ratio vessel bioreactor). This small-aspect ratio means that a simple
      idealized model may be considered, in which (leading order) quantities are
      averaged across the axial direction. The leading-order fluid flow is then of Hele
      Shaw type, and may be solved for explicitly. The trajectory of the tissue
      construct within the rotating bioreactor is determined by analysis of the various
      forces acting on it. Several different modes of motion are found to be possible,
      depending on the experimental conditions, and examples of each type of motion are
      presented. Additionally, we solve the problem for the nutrient transport around
      the tissue construct in the special case in which the construct remains fixed in
      the laboratory frame, and (as the cells proliferate in response to the nutrient
      available locally) deduce growth rates for the construct. Finally, we discuss our
      results in the light of possible experimental bioreactor set-ups. We note the
      present model's limitations, and consider how our work could be extended and
      improved to inform experimental protocols in future.

PMID- 17043082
TI  - Neural populations can induce reliable postsynaptic currents without observable
      spike rate changes or precise spike timing.
AB  - Fine temporal patterns of firing in much of the brain are highly irregular. In
      some circuits, the precise pattern of irregularity contains information beyond
      that contained in mean firing rates. However, the capacity of neural circuits to
      use this additional information for computational purposes is not well
      understood. Here we employ computational methods to show that an ensemble of
      neurons firing at a constant mean rate can induce arbitrarily chosen temporal
      current patterns in postsynaptic cells. If the presynaptic neurons fire with
      nearly uniform interspike intervals, then current patterns are sensitive to
      variations in spike timing. But irregular, Poisson-like firing can drive current
      patterns robustly, even if spike timing varies by tens of milliseconds from trial
      to trial. Notably, irregular firing patterns can drive useful patterns of current
      even if they are so variable that several hundred repeated experimental trials
      would be needed to distinguish them from random firing. Together, these results
      describe an unrestrictive set of conditions in which postsynaptic cells might
      exploit virtually any information contained in spike timing. We speculate as to
      how this capability may underlie an extension of population coding to the
      temporal domain.

PMID- 17043084
TI  - Molecular interaction between Methylobacterium extorquens and seedlings: growth
      promotion, methanol consumption, and localization of the methanol emission site.
AB  - Four Methylobacterium extorquens strains were isolated from strawberry (Fragaria
      x ananassa cv. Elsanta) leaves, and one strain, called ME4, was tested for its
      ability to promote the growth of various plant seedlings. Seedling weight and
      shoot length of Nicotiana tabacum, Lycopersicon esculentum, Sinapis alba, and
      Fragaria vesca increased significantly in the presence of the pink-pigmented
      facultative methylotroph (PPFM), but the germination behaviour of seeds from six
      other plants was not affected. The cell-free supernatant of the bacterial culture
      stimulated germination, suggesting the production of a growth-promoting agent by
      the methylotroph. Methanol emitted from N. tabacum seedlings, as determined by
      proton-transfer-reaction mass spectrometry (PTR-MS), ranged from 0.4 to 0.7 ppbv
      (parts per billion by volume), while significantly lower levels (0.005 to 0.01
      ppbv) of the volatile alcohol were measured when the seedlings were co-cultivated
      with M. extorquens ME4, demonstrating the consumption of the gaseous methanol by
      the bacteria. Additionally, by using cells of the methylotrophic yeast Pichia
      pastoris transformed with the pPICHS/GFP vector harbouring a methanol-sensitive
      promoter in combination with the green fluorescence protein (GFP) reporter gene,
      stomata were identified as the main source of the methanol emission on tobacco
      cotyledons. Methylobacterium extorquens strains can nourish themselves using the
      methanol released by the stomata and release an agent promoting the growth of the
      seedlings of some crop plants.

PMID- 17043083
TI  - The apoplastic antioxidant system in Prunus: response to long-term plum pox virus
      infection.
AB  - This work describes, for the first time, the changes taking place in the
      antioxidative system of the leaf apoplast in response to plum pox virus (PPV) in
      different Prunus species showing different susceptibilities to PPV. The presence
      of p-hydroxymercuribenzoic acid (pHMB)-sensitive ascorbate peroxidase (APX)
      (class I APX) and pHMB-insensitive APX (class III APX), superoxide dismutase
      (SOD), peroxidase (POX), NADH-POX, and polyphenoloxidase (PPO) was described in
      the apoplast from both peach and apricot leaves. PPV infection produced different
      changes in the antioxidant system of the leaf apoplast from the Prunus species,
      depending on their susceptibility to the virus. In leaves of the very susceptible
      peach cultivar GF305, PPV brought about an increase in class I APX, POX, NADH
      POX, and PPO activities. In the susceptible apricot cultivar Real Fino, PPV
      infection produced a decrease in apoplastic POX and SOD activities, whereas a
      strong increase in PPO was observed. However, in the resistant apricot cultivar
      Stark Early Orange, a rise in class I APX as well as a strong increase in POX and
      SOD activities was noticed in the apoplastic compartment. Long-term PPV infection
      produced an oxidative stress in the apoplastic space from apricot and peach
      plants, as observed by the increase in H2O2 contents in this compartment.
      However, this increase was much higher in the PPV-susceptible plants than in the
      resistant apricot cultivar. Only in the PPV-susceptible apricot and peach plants
      was the increase in apoplastic H2O2 levels accompanied by an increase in
      electrolyte leakage. No changes in the electrolyte leakage were observed in the
      PPV-inoculated resistant apricot leaves, although a 42% increase in the
      apoplastic H2O2 levels was produced. Two-dimensional electrophoresis analyses
      revealed that the majority of the polypeptides in the apoplastic fluid had
      isoelectric points in the range of pI 4-6. The identification of proteins using
      MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) and
      peptide mass fingerprinting analyses showed the induction of a thaumatin-like
      protein as well as the decrease of mandelonitrile lyase in peach apoplast due to
      PPV infection. However, most of the selected polypeptides showed no homology with
      known proteins. This fact emphasizes that, at least in Prunus, most of the
      functions of the apoplastic space remain unknown. It is concluded that long-term
      PPV infection produced an oxidative stress in the leaf apoplast, contributing to
      the deleterious effects produced by PPV infection in leaves of inoculated,
      susceptible Prunus plants.

PMID- 17043085
TI  - Leaf hairs influence phytopathogenic fungus infection and confer an increased
      resistance when expressing a Trichoderma alpha-1,3-glucanase.
AB  - The leaf surface of a very large number of plant species are covered by
      trichomes. Non-glandular trichomes are specialized unicellular or multicellular
      structures that occur in many different plant species and function in xenobiotic
      detoxification and protecting the plant against pest attack. By analysing the
      susceptibility of trichome mutants, evidence is provided that indicates the
      influence of leaf trichomes on foliar fungal infections in Arabidopsis thaliana,
      probably by facilitating the adhesion of the fungal spores/hyphae to the leaf
      surface. A decreased trichome number in the hairless Arabidopsis mutant gl1
      enhances tolerance against the necrotrophic fungus Botrytis cinerea. By contrast,
      the try mutant shows an increased susceptibility to both fungal infection and
      accumulation. Trichome density does not influence infection by the soil-borne
      pathogen Rhizoctonia solani. In addition, the influence of trichomes on foliar
      infection is supported by targeting the high-level expression of the Trichoderma
      harzianum alpha-1,3-glucanase protein to the specialized cell structures.
      Trichome expression of this anti-fungal hydrolase shows a significant resistance
      to infection by the foliar pathogen Botrytis cinerea. Resistance to this fungus
      is not dependent on the constitutive induction of the salicylic or jasmonic
      defence signalling pathways, but the presence of the alpha-1,3-glucanase protein
      in trichomes.

PMID- 17043086
TI  - Expression profiling of Chondrus crispus (Rhodophyta) after exposure to methyl
      jasmonate.
AB  - Methyl jasmonate (MeJA) is a plant hormone important for the mediation of signals
      for developmental processes and defence reactions in higher plants. The effects
      of MeJA and the signalling pathways on other photosynthetic organism groups are
      largely unknown, even though MeJA may have very important roles. Therefore the
      effects of MeJA in a red alga were studied. A medium-scale expression profiling
      approach to identify genes regulated by MeJA in the red seaweed Chondrus crispus
      is described here. The expression profiles were studied 0, 2, 4, 6, 12, and 24 h
      after the addition of MeJA to the seawater surrounding the algae. The changes in
      the transcriptome were monitored using cDNA microarrays with 1920 different cDNA
      representing 1295 unique genes. The responses of selected genes were verified
      with real-time PCR and the correlation between the two methods was generally
      satisfying. The study showed that 6% of genes studied showed a response to the
      addition of MeJA and the most dynamic response was seen after 6 h. Genes that
      showed up-regulation included several glutathione S-transferases, heat shock
      protein 20, a xenobiotic reductase, and phycocyanin lyase. Down-regulated
      transcripts included glucose kinase, phosphoglucose isomerase, and a ribosomal
      protein. A comparison between different functional groups showed an up-regulation
      of stress-related genes and a down-regulation of genes involved in energy
      conversion and general metabolism. It is concluded that MeJA, or a related
      compound, has a physiological role as a stress hormone in red algae. This study
      represents to our knowledge the first analysis of gene expression using cDNA
      microarrays in a red macroalga.

PMID- 17043087
TI  - MtArt: a new model of amino acid replacement for Arthropoda.
AB  - A statistical approach was applied to select those models that best fit each
      individual mitochondrial (mt) protein at different taxonomic levels of metazoans.
      The existing mitochondrial replacement matrices, MtREV and MtMam, were found to
      be the best-fit models for the mt-proteins of vertebrates, with the exception of
      Nd6, at different taxonomic levels. Remarkably, existing mitochondrial matrices
      generally failed to best-fit invertebrate mt-proteins. In an attempt to better
      model the evolution of invertebrate mt-proteins, a new replacement matrix, named
      MtArt, was constructed based on arthropod mt-proteomes. The new model was found
      to best fit almost all analyzed invertebrate mt-protein data sets. The observed
      pattern of model fit across the different data sets indicates that no single
      replacement matrix is able to describe the general evolutionary properties of mt
      proteins but rather that taxonomical biases and/or the existence of different mt
      genetic codes have great influence on which model is selected.

PMID- 17043088
TI  - Protein-energy supplements to preserve nutritional status of sugar cane cutters.
AB  - BACKGROUND: Sugar cane cutters in south-eastern Brazil are temporarily hired for
      the harvest period of 8 months. They often have minimal benefits and may not
      receive adequate nutrition. AIMS: To evaluate alterations in weight and body
      composition of sugar cane cutters during harvest with the use of protein-energy
      and electrolyte supplements. METHODS: Three products were used daily: a milk
      drink, a seasoned manioc meal mixture and an electrolyte replacement fluid,
      adding approximately 398 kcal and 28.5 g of protein/day. RESULTS: There were
      small, but significant, reductions in body mass index and percentage body fat
      with maintenance of lean mass. There was a significant improvement in hydration
      status, serum albumin and cholesterol. There were no medical absences related to
      dehydration. CONCLUSIONS: Even though alterations in body mass and biochemistry
      were small, the significance of the findings suggests these supplements may have
      a useful role to play in reducing lean mass losses and maintaining nutritional
      and hydration status of these workers.

PMID- 17043089
TI  - Activity, functional capacity and well-being in ageing Finnish workers.
AB  - BACKGROUND: The ageing of the labour force and falling employment rates have
      forced policy makers in industrialized countries to find means of increasing the
      well-being of older workers and of lengthening their work careers. AIMS: To
      longitudinally study the relationship between activity and functional capacity
      and the well-being of ageing workers. METHODS: Follow-up study to that carried
      out by the Finnish Institute of Occupational Health in 1981-97 (n = 3817).
      Activity level was measured using various free-time activities, and functional
      capacity was measured through daily-life activities. The measure of well-being
      included items with both positive and negative affects. The associations between
      activity, functional capacity and well-being were analysed by general linear
      models with repeated measures. RESULTS: Activity level and functional capacity
      had a strong positive effect (the effects of one unit increase were 0.32 and
      0.30, respectively) on well-being. They were also interdependent. The impact of
      activity level in maintaining well-being became 31% greater during the follow-up,
      whereas the effect of functional capacity diminished by 17%. CONCLUSION: The
      results of the study indicate that both involvement in activities and functional
      capacity have an important, partly compensatory role in maintaining the well
      being of ageing workers.

PMID- 17043090
TI  - Effects of overtime work on blood pressure and body mass index in Japanese male
      workers.
AB  - BACKGROUND: Effects of overtime work on health is a controversial issue. AIMS: To
      determine the effects of overtime work on blood pressure and body mass index
      (BMI) for male workers in Japan. METHODS: Participants were 323 male participants
      of three companies. Data were collected by occupational physicians at periodic
      physical examinations and additional examinations. The time courses for the
      development of definite hypertension and an increase in BMI were recorded. The
      Kaplan-Meier method was used to estimate the cumulative incidence rates of
      developing definite hypertension and increasing BMI, and the Cox proportional
      hazard model was used to determine the adjusted relative hazard of overtime work.
      RESULTS: The age-adjusted incidence rates of developing definite hypertension and
      increasing BMI were significantly lower among the participants whose mean
      overtime was > or =50 h than among those whose mean overtime was <50 h/month (log
      rank P < 0.05). The Cox proportional hazard model indicated that those who worked
      a mean overtime of > or =50 h/month had lower risks of developing definite
      hypertension (hazard ratio, 0.36; 95% CI, 0.15-0.88; P < 0.05) and increasing
      their BMI (hazard ratio, 0.44; 95% CI, 0.31-0.63; P < 0.01) after adjusting for
      age. CONCLUSIONS: The results of this study indicate that workers whose mean
      overtime was > or =50 h have lower risks of developing definite hypertension and
      increasing their BMI.

PMID- 17043091
TI  - Clinicopathological features of pyothorax-associated lymphoma; a retrospective
      survey involving 98 patients.
AB  - To investigate clinicopathological features of pyothorax-associated lymphoma
      (PAL), we examined medical records of 98 patients (88 males and 10 females) with
      PAL at a median age of 70 years (range 51-86). Seventy-nine patients had a
      history of artificial pneumothorax. Median interval between diagnosis and
      artificial pneumothorax was 43 years (range 19-64). At diagnosis, performance
      status (PS) was 0-1 (n=56) and 2-4 (n=42). Clinical stages were I (n=42), II
      (n=26), III (n=8) and IV (n=22). Pathological diagnosis comprised diffuse large-B
      cell (n=78) and peripheral T-cell lymphoma (n=1). Seventeen were treated
      supportively. The other 81 received aggressive treatments; chemotherapy (n=52),
      radiotherapy (n=7), surgery (n=4) and combination (n=18). Five-year overall
      survival (OS) was 0.35 (95% confidence interval, 24% to 45%). Causes of deaths
      were PAL (n=39), respiratory failure (n=13) and others (n=12). Multivariate
      analysis identified prognostic factors for OS; lactate dehydrogenase levels
      [hazard ratio (HR)=2.36; P=0.013], sex (female versus male) (HR=0.15; P=0.01), PS
      (2-4 versus 0-1) (HR=2.20; P=0.02), clinical stages (III/IV versus I/II)
      (HR=1.95; P=0.037) and chemotherapy (HR=0.31; P=0.01). Most patients with PAL are
      elderly and have comorbidities, while some of them achieve durable remission with
      appropriate treatments. These findings prompt us to establish an optimal
      treatment strategy on the basis of risk stratification of individual patients.

PMID- 17043092
TI  - Predicting prognosis in patients with advanced cancer.
AB  - BACKGROUND: Patients with advanced cancer and their carers frequently wish to
      know how long they can expect to live. Improved prognostication would enable
      patients and their carers to be better prepared for their impending death, and
      would allow clinicians to make better informed decisions about place of care.
      However, clinician estimates of survival are inaccurate and systematically
      overoptimistic. Recently, attempts have been made to improve upon clinician
      estimates of survival by devising prognostic scales incorporating clinical
      information with biochemical and haematological results. DESIGN: A descriptive
      and critical review of palliative prognostic scales, on the basis of the
      recommendations of the European Association of Palliative Care prognosis working
      group (2005) supplemented by an Ovid Medline search 1966-March 2006 using the key
      words 'prognosis', 'neoplasms', 'palliative care' and 'terminal care'. RESULTS:
      This paper reviews the advantages and limitations of the palliative prognostic
      score, the palliative prognostic index, the Chuang prognostic scale, the terminal
      cancer prognostic score and the poor prognostic indicator. CONCLUSIONS: All the
      currently available prognostic scales have limitations, but nonetheless offer an
      improvement on unadjusted clinician estimates of survival. Further research is
      required to systematically develop a prognostic scale on the basis of all the
      known prognostic variables in patients with advanced cancer.

PMID- 17043093
TI  - The cost-effectiveness of bisphosphonates in metastatic breast cancer: letter to
      the editor in response to Botteman et al. 2006.

PMID- 17043094
TI  - Randomized phase II trial of gemcitabine plus weekly versus three-weekly
      paclitaxel in previously untreated advanced non-small-cell lung cancer.
AB  - INTRODUCTION: Gemcitabine and paclitaxel (Taxol) each provides an efficacious non
      platinum option for the treatment of advanced non-small-cell lung cancer (NSCLC),
      but the optimal dosage and schedule of the two agents used in combination are not
      well defined. METHODS: Previously untreated patients with advanced NSCLC were
      randomized to receive gemcitabine-paclitaxel on a traditional three-weekly
      schedule (Arm A) or a novel weekly schedule (Arm B) as follows-Arm A (three
      weekly): gemcitabine 1000 mg/m2 infused>30 min on days 1 and 8 and paclitaxel 200
      mg/m2 infused>3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000
      mg/m2 infused>30 min and paclitaxel 100 mg/m2 infused>1 h, both administered on
      days 1 and 8 of a 21-day cycle. RESULTS: One hundred patients received at least
      one dose of treatment. The weekly schedule, Arm B, was more efficacious and less
      hematologically toxic than Arm A. Confirmed complete and partial response rates
      were 28.2% and 26.8%, respectively. Median survival was 10.3 months on Arm B and
      7.9 months on Arm A (log-rank P=0.10); 1- and 2-year survival rates also favor
      Arm B: 42.0% versus 34.0% and 18.0% versus 6.0%. Progression-free survival was
      5.8 versus 4.8 months, again favoring Arm B (log-rank P=0.06). There was a two
      fold lower frequency of grade 3/4 hematologic events with Arm B as follows:
      neutropenia (16% versus 30%), thrombocytopenia (4% versus 8%), and anemia (2%
      versus 6%). One patient (2%) in each treatment group developed febrile
      neutropenia. CONCLUSION: In this trial, both schedules were efficacious and
      tolerable, although the weekly schedule resulted in improved survival and lower
      hematologic toxicity compared with a three-weekly schedule. The weekly schedule
      of gemcitabine-paclitaxel indicates an improved therapeutic index.

PMID- 17043095
TI  - Henoch-Schonlein purpura (HSP) during treatment with anastrozole.

PMID- 17043096
TI  - Artificial sweeteners and cancer risk in a network of case-control studies.
AB  - BACKGROUND: The role of sweeteners on cancer risk has been widely debated over
      the last few decades. To provide additional information on saccharin and other
      sweeteners (mainly aspartame), we considered data from a large network of case
      control studies. METHODS: An integrated network of case-control studies has been
      conducted between 1991 and 2004 in Italy. Cases were 598 patients with incident,
      histologically confirmed cancers of the oral cavity and pharynx, 304 of the
      oesophagus, 1225 of the colon, 728 of the rectum, 460 of the larynx, 2569 of the
      breast, 1031 of the ovary, 1294 of the prostate and 767 of the kidney (renal cell
      carcinoma). Controls were 7028 patients (3301 men and 3727 women) admitted to the
      same hospitals as cases for acute, non-neoplastic disorders. Odds ratios (ORs),
      and the corresponding 95% confidence intervals (CIs), were derived by
      unconditional logistic regression models. RESULTS: The ORs for consumption of
      saccharin were 0.83 (95% CI 0.30-2.29) for cancers of the oral cavity and
      pharynx, 1.58 (95% CI 0.59-4.25) for oesophageal, 0.95 (95% CI 0.67-1.35) for
      colon, 0.93 (95% CI 0.60-1.45) for rectal, 1.55 (95% CI 0.76-3.16) for laryngeal,
      1.01 (95% CI 0.77-1.33) for breast, 0.46 (95% CI 0.29-0.74) for ovarian, 0.91
      (95% CI 0.59-1.40) for prostate and 0.79 (95% CI 0.49-1.28) for kidney cancer.
      The ORs for consumption of other sweeteners, mainly aspartame, were 0.77 (95% CI
      0.39-1.53) for cancers of the oral cavity and pharynx, 0.77 (95% CI 0.34-1.75)
      for oesophageal, 0.90 (95% CI 0.70-1.16) for colon, 0.71 (95% CI 0.50-1.02) for
      rectal, 1.62 (95% CI 0.84-3.14) for laryngeal, 0.80 (95% CI 0.65-0.97) for
      breast, 0.75 (95% CI 0.56-1.00) for ovarian, 1.23 (95% CI 0.86-1.76) for prostate
      and 1.03 (95% CI 0.73-1.46) for kidney cancer. A significant inverse trend in
      risk for increasing categories of total sweeteners was found for breast and
      ovarian cancer, and a direct one for laryngeal cancer. CONCLUSION: The present
      work indicates a lack of association between saccharin, aspartame and other
      sweeteners and the risk of several common neoplasms.

PMID- 17043097
TI  - Role of fluorodeoxyglucose positron emission tomography in the staging of
      patients with breast cancer candidated to surgery.

PMID- 17043098
TI  - Chemical genomic profiling for identifying intracellular targets of toxicants
      producing Parkinson's disease.
AB  - The yeast deletion collection includes approximately 4700 strains deleted for
      both copies of every nonessential gene. This collection is a powerful resource
      for identifying the cellular pathways that functionally interact with drugs. In
      the present study, the complete pool of approximately 4700 barcoded homozygous
      deletion strains of Saccharomyces cerevisiae were surveyed to identify
      genes/pathways interacting with 1-methyl-4-phenylpyridinium (MPP(+)) and N,N
      dimethyl-4-4-bipiridinium (paraquat), neurotoxicants that can produce Parkinson's
      disease. Each yeast mutant is molecularly "barcoded" the collections can be grown
      competitively and ranked for sensitivity by microarray hybridization. Analysis
      data from these screens allowed us to determine that the multivesicular body
      pathway is an important element of toxicity induced by both MPP(+) and paraquat.
      When yeast genes that when deleted showed sensitivity to MPP(+) and paraquat
      toxicity were analyzed for their homology to human genes, 80% were found to have
      highly conserved human homologs (with e < 10(-8)). Future work will address if
      these human genes may also functionally interact with MPP(+) and paraquat
      toxicity.

PMID- 17043099
TI  - Human oviductal epithelial cells express Toll-like receptor 3 and respond to
      double-stranded RNA: Fallopian tube-specific mucosal immunity against viral
      infection.
AB  - BACKGROUND: The aim of this study was to evaluate the site-specific
      immunoregulatory mechanisms against viral infection in human Fallopian tubes.
      METHODS: We therefore investigated the effects of double-stranded RNA (dsRNA) on
      the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2
      (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked
      immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha)
      protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3
      in these cells were also evaluated by western blot analysis. RESULTS:
      Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that
      antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly
      I:C-induced production of these cytokines by OECs was inhibited by the
      pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of
      IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The
      expression of TLR3 was also detected in OECs. CONCLUSION: These results suggest
      that the epithelial cells of the human Fallopian tube have evolved a unique, site
      specific mechanism for recognizing viral infection. TLR3-mediated production of
      proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may
      be important for antiviral immunity in the human female reproductive tract.

PMID- 17043100
TI  - Menstrual cycle-dependent changes of Toll-like receptors in endometrium.
AB  - BACKGROUND: Rapid innate immune defences against infection usually involve the
      recognition of invading pathogens by specific pattern recognition receptors
      recently attributed to the family of Toll-like receptors (TLRs). Reports from our
      laboratory and others have demonstrated the existence of TLRs 1-6 in the female
      reproductive tract. However, little has been done to identify TLRs 7-10 in the
      female reproductive tract, particularly in the uterus. Also little information
      exists regarding variation in TLRs in the female reproductive tract during the
      menstrual cycle. METHOD: The distribution of TLR7-10 protein was detected by
      immunostaining in timed endometrial biopsies from normal women. RT-PCR was used
      to show the existence of TLR1-10 genes in endometrial tissue and real-time PCR
      analysis to investigate the relative expression of these genes during the
      menstrual cycle in normal human endometrium. RESULTS: TLR7-10 proteins were
      detected in endometrial epithelium and stroma. TLR1-10 genes were expressed in
      human endometrial tissue, and the mean relative expression of TLR2-6, 9 and 10
      genes was significantly higher during the secretory phase compared with other
      phases of the menstrual cycle. CONCLUSIONS: TLR7-10 localization is not limited
      to endometrial epithelium but is also present in the stroma of the endometrial
      tissue. Endometrial TLR2-6, 9 and 10 genes are cyclically expressed during the
      menstrual cycle.

PMID- 17043101
TI  - Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection.
AB  - Gastrointestinal nematode infections are prevalent worldwide and are potent
      inducers of T helper 2 responses with the capacity to modulate the immune
      response to heterologous antigens. Parasitic helminth infection has even been
      shown to modulate the immune response associated with autoimmune diseases.
      Nonobese diabetic (NOD) mice provide a model for studying human autoimmune
      diabetes; as in humans, the development of diabetes in NOD mice has been linked
      to the loss of self-tolerance to beta cell autoantigens. Previous studies with
      the NOD mouse have shown that helminth and bacterial infection appears to inhibit
      type 1 diabetes by disrupting the pathways leading to the Th1-mediated
      destruction of insulin-producing beta cells. The aim of our study was to examine
      whether infection with the gastrointestinal helminths Trichinella spiralis or
      Heligmosomoides polygyrus could inhibit the development of autoimmune diabetes in
      NOD mice and to analyze the mechanisms involved in protection and the role of Th2
      responses. Protection from diabetes was afforded by helminth infection, appeared
      to inhibit autoimmune diabetes by disrupting pathways leading to the destruction
      of beta cells, and was mediated by seemingly independent mechanisms depending on
      the parasite but which may be to be related to the capacity of the host to mount
      a Th2 response.

PMID- 17043102
TI  - Proteolytic processing of the Cryptosporidium glycoprotein gp40/15 by human furin
      and by a parasite-derived furin-like protease activity.
AB  - The apicomplexan parasite Cryptosporidium causes diarrheal disease worldwide.
      Proteolytic processing of proteins plays a significant role in host cell invasion
      by apicomplexan parasites. In previous studies, we described gp40/15, a
      Cryptosporidium sp. glycoprotein that is proteolytically cleaved to yield two
      surface glycopeptides (gp40 and gp15), which are implicated in mediating
      infection of host cells. In the present study, we showed that biosynthetically
      labeled gp40/15 is processed in Cryptosporidium parvum-infected HCT-8 cells. We
      identified a putative furin cleavage site RSRR downward arrow in the deduced
      amino acid sequence of gp40/15 from C. parvum and from all Cryptosporidium
      hominis subtypes except subtype 1e. Both human furin and a protease activity
      present in a C. parvum lysate cleaved recombinant C. parvum gp40/15 protein into
      2 peptides, identified as gp40 and gp15 by size and by immunoreactivity with
      specific antibodies. C. hominis gp40/15 subtype 1e, in which the RSRR sequence is
      replaced by ISKR, has an alternative furin cleavage site (KSISKR downward arrow)
      and was also cleaved by both furin and the C. parvum lysate. Site-directed
      mutagenesis of the C. parvum RSRR sequence to ASRR resulted in inhibition of
      cleavage by furin and the C. parvum lysate. Cleavage of recombinant gp40/15 and a
      synthetic furin substrate by the C. parvum lysate was inhibited by serine
      protease inhibitors, by the specific furin inhibitor decanoyl-Arg-Val-Lys-Arg
      chloromethylketone (Dec-RVKR-cmk), and by calcium chelators, suggesting that the
      parasite expresses a Ca2+ dependent, furin-like protease activity. The furin
      inhibitor Dec-RVKR-cmk decreased C. parvum infection of HCT-8 cells, suggesting
      that a furin-like protease activity may be involved in mediating host-parasite
      interactions.

PMID- 17043103
TI  - Protein P200 is dispensable for Mycoplasma pneumoniae hemadsorption but not
      gliding motility or colonization of differentiated bronchial epithelium.
AB  - Mycoplasma pneumoniae protein P200 was localized to the terminal organelle, which
      functions in cytadherence and gliding motility. The loss of P200 had no impact on
      binding to erythrocytes and A549 cells but resulted in impaired gliding motility
      and colonization of differentiated bronchial epithelium. Thus, gliding may be
      necessary to overcome mucociliary clearance.

PMID- 17043104
TI  - Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular
      polysaccharide type 14 cross-reactive antigen that induces protective
      immunoglobulin responses against pneumococcal infection in mice.
AB  - Exosomes activate T cells in vivo, but whether exosomes are able to induce
      humoral immune responses is still unknown. We found that dendritic cells, but not
      other immune cells, constitutively release an exosome-associated glycoconjugate
      that is cross-reactive with the capsular polysaccharide of Streptococcus
      pneumoniae type 14 (Cps14-CRA). Cps14-CRA was localized to the cholesterol
      enriched microdomains or rafts of the exosomes and was mapped to the beta1-->6
      branched N-acetyl-lactosamine derivatives of the Cps14-CRA. Injection of CFA
      primed naive mice with purified dendritic cell exosomes induced immunoglobulin
      (Ig) anti-Cps14 responses composed predominantly of IgM, IgG3, and IgG1. These
      responses were associated with protection against a lethal challenge with live S.
      pneumoniae type 14, but not with type 3 bacteria, and was correlated with the
      titer of elicited IgM and IgG3 anti-Cps14. These data show, for the first time,
      that exosomes can induce a humoral immune response to an associated unprocessed,
      autologous antigen. Although anti-Cps14 Ig responses are specifically
      demonstrated, these could reflect a broader mechanism that modulates both natural
      immunity and autoimmunity to other glycotopes.

PMID- 17043105
TI  - Limited role for CD4+ T-cell help in the initial priming of Trypanosoma cruzi
      specific CD8+ T cells.
AB  - Immune control of the protozoan parasite Trypanosoma cruzi requires the
      activation of both CD4+ and CD8+ T cells. We recently identified two T. cruzi
      trans-sialidase peptides that are targets of approximately 30% of all CD8+ T
      cells during acute T. cruzi infection in mice. To determine whether CD4+ T cells
      are required for generation of these dominant CD8+ T-cell responses, major
      histocompatibility complex class II (MHC II)-deficient mice were infected with
      the Brazil strain of T. cruzi and examined for the generation of antigen-specific
      CD8+ T cells. Strong trans-sialidase TSKB18- and TSKB20-specific CD8+ T-cell
      responses were generated in both the presence and the absence of CD4+ help.
      However, the magnitudes of the immunodominant TSKB20-specific CD8+ T-cell
      responses detectable using class I MHC-peptide tetramers were consistently lower
      in the blood and spleens of MHC II-deficient mice. Spleen cells from infected MHC
      II-deficient mice produced gamma interferon after in vitro stimulation with T.
      cruzi peptides at levels similar to those in wild-type mice, and MHC II-deficient
      mice displayed strong T. cruzi peptide-specific cytotoxic T-lymphocyte activity
      in vivo. Thus, primary CD8+ T-cell responses in experimental T. cruzi infection
      are generated in the absence of CD4+ T cells, providing further evidence that T.
      cruzi directly activates and licenses antigen-presenting cells. Nevertheless,
      unhelped CD8+ T cells in T. cruzi-infected mice fail to reach the frequencies
      achieved in the presence of CD4 T-cell help and are unable to prevent acute-phase
      death of these mice.

PMID- 17043106
TI  - Serratia marcescens serralysin induces inflammatory responses through protease
      activated receptor 2.
AB  - The Serratia marcescens-derived protease serralysin is considered to play an
      important role in the pathogenesis of infection. Protease-activated receptor 2
      (PAR-2) is activated by trypsin and also several other trypsin-like serine
      proteases, leading to the modulation of inflammatory and immune responses.
      However, little is known about the activation of PAR-2 by bacterial proteases and
      its roles in bacterial infection. In this study, we investigated whether S.
      marcescens serralysin activates host inflammatory responses through PAR-2. Our
      results demonstrated that serralysin induces interleukin-6 (IL-6) and IL-8 mRNA
      expression in a human lung squamous cell carcinoma, EBC-l cells. In addition,
      serralysin activated activator protein 1 (AP-1)-, CCAAT/enhancer-binding protein
      (C/EBP)-, and nuclear factor-kappaB (NF-kappaB)-driven promoters in EBC-1 cells.
      An electrophoretic mobility shift assay showed that serralysin activates the
      binding of AP-1, C/EBPbeta, and NF-kappaB in the cells. Inactivation of
      serralysin resulted in the failure of transactivation of AP-1-, C/EBP-, and NF
      kappaB-driven promoters in the cells. Furthermore, serralysin activated AP-1-,
      C/EBP-, and NF-kappaB-driven promoters via PAR-2 in HeLa cells. PAR-2 antagonist
      peptides decreased serralysin-induced transactivation of AP-1-, C/EBP-, and NF
      kappaB-driven promoters in EBC-1 cells. Considered together, these results
      suggest that serralysin requires PAR-2 to activate the critical transcription
      factors AP-1, C/EBPbeta, and NF-kappaB for host inflammatory responses.

PMID- 17043107
TI  - High levels of CXCL10 are produced by intestinal epithelial cells in AIDS
      patients with active cryptosporidiosis but not after reconstitution of immunity.
AB  - Chemokines play key roles in attracting immune cells to sites of infections.
      However, few data on chemokine expression in the gut during human infections are
      available. We examined expression of chemokines in intestinal tissues of AIDS
      patients during active Cryptosporidium infection and during resolution of such an
      infection. The chemokines and cytokines in cell lysates from jejunal biopsy
      tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its
      receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies
      from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11
      [eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and
      three cytokines (interleukin-1alpha [IL-1alpha], IL-10, and granulocyte colony
      stimulating factor) were detected. The level of CXCL10 was significantly
      increased in AIDS patients with cryptosporidiosis compared to the level in AIDS
      patients without cryptosporidiosis or in normal volunteers (median in AIDS
      patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72
      pg/mg protein in AIDS patients without cryptosporidiosis and in normal
      volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by
      a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden
      (as measured by the number of Cryptosporidium oocysts in the stools) and also
      with the IL-1alpha concentration (Pearson correlation values, 0.961 [P < 0.01]
      and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to
      epithelial cells at the site of infection. Following effective antiparasite and
      antiretroviral therapy, Cryptosporidium infections resolved, and the levels of
      CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important
      role in the resolution of cryptosporidiosis by attracting immune effector cells
      to the site of infection. By contrast, in AIDS patients lacking effector cells,
      CXCL10 may contribute to the immunopathogenesis by recruiting inflammatory cells.

PMID- 17043108
TI  - The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are
      regulated by CARM1-dependent methylation.
AB  - The transcriptional coactivator p/CIP(SRC-3/AIB1/ACTR/RAC3) binds liganded
      nuclear hormone receptors and facilitates transcription by directly recruiting
      accessory factors such as acetyltransferase CBP/p300 and the coactivator arginine
      methyltransferase CARM1. In the present study, we have established that
      recombinant p/CIP (p300/CBP interacting protein) is robustly methylated by CARM1
      in vitro but not by other protein arginine methyltransferase family members.
      Metabolic labeling of MCF-7 breast cancer cells with S-adenosyl-L-[methyl
      (3)H]methionine and immunoblotting using dimethyl arginine-specific antibodies
      demonstrated that p/CIP is specifically methylated in intact cells. In addition,
      methylation of full-length p/CIP is not supported by extracts derived from CARM1(
      /-) mouse embryo fibroblasts, indicating that CARM1 is required for p/CIP
      methylation. Using mass spectrometry, we have identified three CARM1-dependent
      methylation sites located in a glutamine-rich region within the carboxy terminus
      of p/CIP which are conserved among all steroid receptor coactivator proteins.
      These results were confirmed by in vitro methylation of p/CIP using carboxy
      terminal truncation mutants and synthetic peptides as substrates for CARM1.
      Analysis of methylation site mutants revealed that arginine methylation causes an
      increase in full-length p/CIP turnover as a result of enhanced degradation.
      Additionally, methylation negatively impacts transcription via a second mechanism
      by impairing the ability of p/CIP to associate with CBP. Collectively, our data
      highlight coactivator methylation as an important regulatory mechanism in
      hormonal signaling.

PMID- 17043110
TI  - Drosophila dCBP is involved in establishing the DNA replication checkpoint.
AB  - The CBP/p300 family of proteins comprises related acetyltransferases that
      coactivate signal-responsive transcription. Recent evidence suggests that
      p300/CBP may also interact directly with complexes that mediate different aspects
      of DNA metabolism such as replication and repair. In this report, we show that
      loss of dCBP in Drosophila cells and eye discs results in a defect in the cell
      cycle arrest induced by stalled DNA replication. We show that dCBP and the
      checkpoint kinase Mei-41 can be found together in a complex and, furthermore,
      that dCBP has a genetic interaction with mei-41 in the response to stalled DNA
      replication. These observations suggest a broader role for the p300/CBP
      acetyltransferases in the modulation of chromatin structure and function during
      DNA metabolic events as well as for transcription.

PMID- 17043109
TI  - The protein arginine methyltransferase Prmt5 is required for myogenesis because
      it facilitates ATP-dependent chromatin remodeling.
AB  - Skeletal muscle differentiation requires the coordinated activity of
      transcription factors, histone modifying enzymes, and ATP-dependent chromatin
      remodeling enzymes. The type II protein arginine methyltransferase Prmt5
      symmetrically dimethylates histones H3 and H4 and numerous nonchromatin proteins,
      and prior work has implicated Prmt5 in transcriptional repression. Here we
      demonstrate that MyoD-induced muscle differentiation requires Prmt5. One of the
      first genes activated during differentiation encodes the myogenic regulator
      myogenin. Prmt5 and dimethylated H3R8 (histone 3 arginine 8) are localized at the
      myogenin promoter in differentiating cells. Modification of H3R8 required Prmt5,
      and reduction of Prmt5 resulted in the abrogation of promoter binding by the Brg1
      ATPase-associated with the SWI/SNF chromatin remodeling enzymes and all
      subsequent events associated with gene activation, including increases in
      chromatin accessibility and stable binding by MyoD. Prmt5 and dimethylated H3R8
      were also associated with the myogenin promoter in activated satellite cells
      isolated from muscle tissue, further demonstrating the physiological relevance of
      these observations. The data indicate that Prmt5 facilitates myogenesis because
      it is required for Brg1-dependent chromatin remodeling and gene activation at a
      locus essential for differentiation. We therefore conclude that a histone
      modifying enzyme is necessary to permit an ATP-dependent chromatin remodeling
      enzyme to function.

PMID- 17043111
TI  - The 6-fluoro-8-methoxy quinolone gatifloxacin down-regulates interleukin-8
      production in prostate cell line PC-3.
AB  - Fluoroquinolones exhibit immunomodulatory effects on monocytes and macrophages,
      in addition to their bactericidal activities. It remains unknown even whether the
      quinolones act directly on the prostate. This study was based on the
      understanding of the molecular mechanisms of the actions of the fluoroquinolones
      that can be used for the treatment of chronic prostatitis/chronic pelvic pain
      syndrome. We investigated whether the 6-fluroro-8-methoxy quinolone gatifloxacin
      (GFLX) affected the production and secretion of interleukin-8 (IL-8) in the
      prostate cell line PC-3. GFLX decreased the level of IL-8 release from
      unstimulated PC-3 cells. GFLX also attenuated IL-8 secretion from PC-3 cells
      stimulated with peptidoglycan, Mycoplasma hominis, phorbol ester, and tumor
      necrosis factor alpha (TNF-alpha), indicating that GFLX exhibits an anti
      inflammatory effect on the prostate cell line. However, GFLX failed to alter
      activation of the NF-kappaB and AP-1 elicited by these stimulants. GFLX
      significantly attenuated the expression of IL-8 mRNA in TNF-alpha-stimulated PC-3
      cells and down-regulated the transcriptional activity of the 5'-flanking region
      of the IL-8 gene from -1481 to +44 bp. The deletion construct without the 5'
      flanking region from -1481 to -170 bp but not the construct without the region
      from -1481 to -188 bp reversed the suppressive effect of GFLX on IL-8 promoter
      activity. These results demonstrate that GFLX suppresses IL-8 expression in the
      prostate cell line by decreasing the promoter activity of the IL-8 gene.

PMID- 17043112
TI  - Susceptibility of acinetobacter strains isolated from deployed U.S. military
      personnel.
AB  - The susceptibilities of 142 Acinetobacter baumannii-calcoaceticus complex
      isolates (95 from wounded U.S. soldiers deployed overseas) to 13 antimicrobial
      agents were determined by broth microdilution. The most active antimicrobial
      agents (> or =95% of isolates susceptible) were colistin, polymyxin B, and
      minocycline.

PMID- 17043113
TI  - Hygromycin B inhibition of protein synthesis and ribosome biogenesis in
      Escherichia coli.
AB  - The aminoglycoside antibiotic hygromycin B was examined in Escherichia coli cells
      for inhibitory effects on translation and ribosomal-subunit formation. Pulse
      chase labeling experiments were performed, which verified lower rates of
      ribosomal-subunit synthesis in drug-treated cells. Hygromycin B exhibited a
      concentration-dependent inhibitory effect on viable-cell numbers, growth rate,
      protein synthesis, and 30S and 50S subunit formation. Unlike other
      aminoglycosides, hygromycin B was a more effective inhibitor of translation than
      of ribosomal-subunit formation in E. coli. Examination of total RNA from treated
      cells showed an increase in RNA corresponding to a precursor to the 16S rRNA,
      while mature 16S rRNA decreased. Northern hybridization to rRNA in cells treated
      with hygromycin B showed that RNase II- and RNase III-deficient strains of E.
      coli accumulated 16S rRNA fragments upon treatment with the drug. The results
      indicate that hygromycin B targets protein synthesis and 30S ribosomal-subunit
      assembly.

PMID- 17043114
TI  - Combination of multiplex PCRs for staphylococcal cassette chromosome mec type
      assignment: rapid identification system for mec, ccr, and major differences in
      junkyard regions.
AB  - Staphylococcal cassette chromosome mec (SCCmec) typing, in combination with
      genotyping of the Staphylococcus aureus chromosome, has become essential for
      defining methicillin-resistant S. aureus (MRSA) clones in epidemiological
      studies. We have developed a convenient system for SCCmec type assignment. The
      system consists of six multiplex PCRs (M-PCRs) for identifying the ccr gene
      complex (ccr), the mec gene complex (mec), and specific structures in the
      junkyard (J) regions: M-PCR with primer set 1 (M-PCR 1) identified five types of
      ccr genes; M-PCR 2 identified class A to class C mec; M-PCRs 3 and 4 identified
      specific open reading frames in the J1 regions of type I and IV and of type II,
      III, and V SCCmec elements, respectively; M-PCR 5 identified the transposons
      Tn554 and PsiTn554 integrated into the J2 regions of type II and III SCCmec
      elements; and M-PCR 6 identified plasmids pT181 and pUB110 integrated into J3
      regions. The system was validated with 99 MRSA strains carrying SCCmec elements
      of different types. The SCCmec types of 93 out of the 99 MRSA strains could be
      assigned. The SCCmec type assignments were identical to those made with a PCR
      system that uses numerous primer pairs to identify genes or gene alleles. Our
      system of six M-PCRs is thus a convenient and reliable method for typing SCCmec
      elements.

PMID- 17043115
TI  - Effect of carbapenem administration on establishment of intestinal colonization
      by vancomycin-resistant enterococci and Klebsiella pneumoniae in mice.
AB  - In a mouse model, ertapenem inhibited the anaerobic intestinal microflora and
      promoted overgrowth of enterococci, whereas imipenem-cilastatin had no effect on
      the indigenous microflora. Ertapenem, but not imipenem-cilastatin, promoted
      modest overgrowth of vancomycin-resistant enterococci when exposure occurred
      during treatment. Neither agent promoted colonization with extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae.

PMID- 17043116
TI  - Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in
      neurointensive care patients with staphylococcal ventriculitis associated with
      external ventricular drains.
AB  - The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five
      neurointensive care patients with staphylococcal ventriculitis was studied. The
      mean area under concentration-time curve (+/- standard deviation) was 63 +/- 18.9
      mg x h/liter, with a CSF-to-plasma ratio of 0.8 +/- 0.3. Times above MIC in CSF
      were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter,
      respectively.

PMID- 17043117
TI  - Quinolone resistance in Helicobacter pylori isolates in Germany.
AB  - We show that quinolone resistance in Helicobacter pylori has reached an alarming
      level in Germany. Our data suggest that the use of quinolones requires prior
      antimicrobial susceptibility testing, especially for isolates from patients who
      have already undergone previous unsuccessful eradication treatments, and also
      underline the further need for surveillance studies to monitor antibiotic
      resistance in H. pylori.

PMID- 17043118
TI  - Effect of anaerobic growth on quinolone lethality with Escherichia coli.
AB  - Quinolone activity against Escherichia coli was examined during aerobic growth,
      aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid,
      norfloxacin, ciprofloxacin, and PD161144 were lethal for cultures growing
      aerobically, and the bacteriostatic activity of each quinolone was unaffected by
      anaerobic growth. However, lethal activity was distinct for each quinolone with
      cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic
      acid failed to kill cells under both conditions; norfloxacin killed cells when
      they were grown anaerobically but not when they were treated with
      chloramphenicol; ciprofloxacin killed cells under both conditions but required
      higher concentrations than those required with cells grown aerobically; and
      PD161144, a C-8-methoxy fluoroquinolone, was equally lethal under all conditions.
      Following pretreatment with nalidixic acid, a shift to anaerobic conditions or
      the addition of chloramphenicol rapidly blocked further cell death. Formation of
      quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS)
      dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic
      growth and in the presence and in the absence of chloramphenicol. However, lethal
      chromosome fragmentation, detected as a drop in viscosity in the absence of SDS,
      occurred with nalidixic acid treatment only under aerobic conditions in the
      absence of chloramphenicol. With PD161144, chromosome fragmentation was detected
      when the cells were grown aerobically and anaerobically and in the presence and
      in the absence of chloramphenicol. Thus, all quinolones tested appear to form
      reversible bacteriostatic complexes containing broken DNA during aerobic growth,
      during anaerobic growth, and when protein synthesis is blocked; however, the
      ability to fragment chromosomes and to rapidly kill cells under these conditions
      depends on quinolone structure.

PMID- 17043119
TI  - Sublethal concentrations of the aminoglycoside amikacin interfere with cell
      division without affecting chromosome dynamics.
AB  - Aminoglycosides bind to the 16S rRNA at the tRNA acceptor site (A site) and
      disturb protein synthesis by inducing codon misreading. We investigated
      Escherichia coli cell elongation and division, as well as the dynamics of
      chromosome replication and segregation, in the presence of sublethal
      concentrations of amikacin (AMK). The fates of the chromosome ori and ter loci
      were monitored by visualization by using derivatives of LacI and TetR fused to
      fluorescent proteins in E. coli strains that carry operator arrays at the
      appropriate locations. The results showed that cultures containing sublethal
      concentrations of AMK contained abnormally elongated cells. The chromosomes in
      these cells were properly located, suggesting that the dynamics of replication
      and segregation were normal. FtsZ, an essential protein in the process of cell
      division, was studied by using an ectopic FtsZ-cyan fluorescent protein fusion.
      Consistent with a defect in cell division, we revealed that the Z ring failed to
      properly assemble in these elongated cells.

PMID- 17043120
TI  - Activity of DX-619 compared to other agents against viridans group streptococci,
      Streptococcus bovis, and Cardiobacterium hominis.
AB  - Against 198 viridans group streptococci, 25 Streptococcus bovis strains, and 5
      Cardiobacterium hominis strains, MICs of DX-619, a des-F(6)-quinolone, were
      between 0.004 and 0.25 microg/ml. These MICs were lower than those of other
      quinolones (< or = 0.008 to > 32 microg/ml). Beta-lactam MICs were between < or =
      0.008 and 16 microg/ml. Azithromycin resistance was found in most species, while
      most were telithromycin susceptible. Glycopeptides and linezolid were active
      against viridans group strains but inactive against C. hominis.

PMID- 17043121
TI  - Comparative bactericidal activities of daptomycin and vancomycin against
      glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA
      isolates.
AB  - Staphylococcus aureus strains from the U.S. SENTRY Antimicrobial Surveillance
      Program, 2002-2003, glycopeptide-intermediate S. aureus (GISA) strains, and
      heterogeneous GISA (hGISA) strains were used to compare bactericidal activities
      of daptomycin and vancomycin using MICs and minimum bactericidal concentrations.
      Glycopeptide-susceptible S. aureus and hGISA strains were further studied by
      using time-kill curves. For all isolates, the daptomycin MIC50 and MIC90 are four
      times lower and the log drops in viable counts at 6 h and 24 h are significantly
      greater than those for vancomycin.

PMID- 17043122
TI  - Combination of amphotericin B with flucytosine is active in vitro against
      flucytosine-resistant isolates of Cryptococcus neoformans.
AB  - The combination of flucytosine and amphotericin B was tested against 10
      flucytosine-resistant isolates of Cryptococcus neoformans by checkerboard,
      killing curves, and Etest. Although differences were observed depending on the
      technique used, antagonism was never observed. The synergistic interaction was
      related to the mechanism of flucytosine resistance of the isolates.

PMID- 17043123
TI  - Pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem, in healthy
      male Caucasian volunteers.
AB  - The CS-023 concentration in plasma after administration by infusion to healthy
      volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the
      cumulative urinary excretion was 59.4% of the dose. The total clearance, renal
      clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2
      liters, respectively.

PMID- 17043124
TI  - Molecular characteristics and in vitro susceptibility to antimicrobial agents,
      including the des-fluoro(6) quinolone DX-619, of Panton-Valentine leucocidin
      positive methicillin-resistant Staphylococcus aureus isolates from the community
      and hospitals.
AB  - Highly virulent, community-acquired methicillin-resistant Staphylococcus aureus
      (MRSA) strains with Panton-Valentine leucocidin (PVL) genes have been found
      increasingly worldwide. Among a total of 2,101 MRSA strains isolated from
      patients in hospitals in Japan, two were positive for PVL genes. One strain was
      identified as a community-acquired MRSA strain with genotype sequence type 30
      (ST30) and spa (staphylococcal protein A gene) type 19 from Japan and was
      resistant only to beta-lactam antimicrobial agents. The other strain was closely
      related to PVL+ multidrug-resistant, hospital-acquired MRSA strains (ST30, spa
      type 43) derived from nosocomial outbreaks in the 1980s to 1990s in Japan but
      with a divergent sequence type, ST765 (a single-locus variant of ST30). Twenty
      two PVL+ MRSA strains, including those from Japan and those from other countries
      with various sequence types (ST1, ST8, ST30, ST59, and ST80) and genotypes, were
      examined for susceptibility to 31 antimicrobial agents. Among the agents, DX-619,
      a des-fluoro(6) quinolone, showed the greatest activity, followed by rifampin and
      sitafloxacin, a fluoroquinolone. The data suggest that DX-619 exhibits a superior
      activity against PVL+ MRSA strains with various virulence genetic traits from the
      community as well as from hospitals.

PMID- 17043125
TI  - Phenotypic and molecular analysis of penicillin-nonsusceptible Streptococcus
      pneumoniae isolates in Poland.
AB  - beta-Lactams are the drugs of choice for the treatment of infections caused by
      the important bacterial pathogen Streptococcus pneumoniae. The recent growth of
      resistance of this organism to penicillin observed worldwide is of the highest
      concern. In this study, using 887 surveillance pneumococcal isolates recovered in
      Poland from 1998 to 2002, we observed the increase in penicillin
      nonsusceptibility from 8.7% to 20.3%. All of the 109 penicillin-nonsusceptible S.
      pneumoniae (PNSP) isolates identified, together with 22 archival PNSP isolates
      from 1995 to 1997, were subsequently analyzed by susceptibility testing,
      serotyping, profiling of pbp genes, pulsed-field gel electrophoresis, and
      multilocus sequence typing (MLST). Four predominant serotypes, serotypes 6B, 9V,
      14, and 23F, characterized 85.5% of the isolates. MLST revealed the presence of
      34 sequence types, 15 of which were novel types. Representatives of seven
      multiresistant international clones (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3,
      Taiwan(23F)-15, Poland(23F)-16, Poland(6B)-20, and Sweden(15A)-25) or their
      closely related variants comprised the majority of the study isolates. The spread
      of Spain(9V)-3 and its related clone of serotype 14/ST143 has remarkably
      contributed to the recent increase in penicillin resistance in pneumococci in the
      country.

PMID- 17043126
TI  - Acyl-substituted dermaseptin S4 derivatives with improved bactericidal
      properties, including on oral microflora.
AB  - The 15-mer dermaseptin S4 derivative S4(1-15) was recently shown to exhibit
      potent activity against oral pathogens associated with caries and periodontitis.
      Here, we investigated possible modes for improving the peptide's properties
      through systematic replacement of an N-terminal amino acid(s) with various fatty
      acids that modulate the peptide's hydrophobicity and/or charge. Deletion of 1 to
      3 residues led to progressive loss of potency as assessed by MIC experiments
      performed on four test bacteria. Replacing the deleted amino acids with fatty
      acids most often resulted in potency recovery or improvement, as evidenced by
      lower MICs and faster bactericidal kinetics in culture media. Best results were
      obtained after replacement of the N-terminal dipeptide alanine-leucine with
      heptanoic (C7) or aminododecanoic (NC12) acid. Circular dichroism analysis
      correlated antibacterial properties to the peptide's secondary structure. MIC
      experiments and confocal laser scanning microscopy results indicated that C7-S4(3
      15) and NC12-S4(3-15) were bactericidal to various oral pathogens, including
      those which are immobilized in a biofilm. C7-S4(3-15) performed similarly to or
      better than (depending on growth medium) IB-367, a peptide assessed in clinical
      trials for treatment of oral mucositis, reducing CFU counts by >3 log units
      within 2 min of incubation. Collectively, the data indicate that substitution of
      fatty acids for amino acids may be a useful strategy in revealing improved
      derivatives of known antimicrobial peptides and suggest the suitability of such
      compounds for controlling pathogens associated with oral diseases.

PMID- 17043127
TI  - Characterization of squalene epoxidase of Saccharomyces cerevisiae by applying
      terbinafine-sensitive variants.
AB  - Squalene epoxidase (SE) is the target of terbinafine, which specifically inhibits
      the fungal enzyme in a noncompetitive manner. On the basis of functional
      homologies to p-hydroxybenzoate hydroxylase (PHBH) from Pseudomonas fluorescens,
      the Erg1 protein contains two flavin adenine dinucleotide (FAD) domains and one
      nucleotide binding (NB) site. By in vitro mutagenesis of the ERG1 gene, which
      codes for the Saccharomyces cerevisiae SE, we isolated erg1 alleles that
      conferred increased terbinafine sensitivity or that showed a lethal phenotype
      when they were expressed in erg1-knockout strain KLN1. All but one of the amino
      acid substitutions affected conserved FAD/nucleotide binding sites. The G(25)S,
      D(335)X (W, F, P), and G(210)A substitutions in the FADI, FADII, and NB sites,
      respectively, rendered the SE variants nonfunctional. The G(30)S and L(37)P
      variants exhibited decreased enzymatic activity, accompanied by a sevenfold
      increase in erg1 mRNA levels and an altered sterol composition, and rendered KLN1
      more sensitive not only to allylamines (10 to 25 times) but also to other
      ergosterol biosynthesis inhibitors. The R(269)G variant exhibited moderately
      reduced SE activity and a 5- to 10-fold increase in allylamine sensitivity but no
      cross-sensitivity to the other ergosterol biosynthesis inhibitors. To further
      elucidate the roles of specific amino acids in SE function and inhibitor
      interaction, a homology model of Erg1p was built on the basis of the crystal
      structure of PHBH. All experimental data obtained with the sensitive Erg1
      variants support this model. In addition, the amino acids responsible for
      terbinafine resistance, although they are distributed along the sequence of
      Erg1p, cluster on the surface of the Erg1p model, giving rise to a putative
      binding site for allylamines.

PMID- 17043128
TI  - Multidrug resistance conferred by novel DNA polymerase mutations in human
      cytomegalovirus isolates.
AB  - The emergence of antiviral-resistant cytomegalovirus (CMV) strains is a
      continuing clinical problem, with increased numbers of immunocompromised patients
      given longer-duration antiviral prophylaxis. Two previously unrecognized CMV DNA
      polymerase mutations (N408K and A834P) identified separately and together in at
      risk lung and kidney transplant recipients and a third mutation (L737M)
      identified in a liver transplant recipient were characterized by marker transfer
      to antiviral-sensitive laboratory strains AD169 and Towne. Subsequent phenotypic
      analyses of recombinant strains demonstrated the ability of mutation N408K to
      confer ganciclovir (GCV) and cidofovir (CDV) resistance and of mutation A834P to
      confer GCV, foscarnet, and CDV resistance. Mutation L737M did not confer
      resistance to any of the antiviral agents tested. A recombinant strain containing
      both N408K and A834P demonstrated increased GCV and CDV resistance compared to
      the levels of resistance of the virus containing only the A834P mutation. The
      addition of mutation N408K in combination with A834P also partially reconstituted
      the replication impairment of recombinant virus containing only A834P. This
      suggests that perturbation of both DNA polymerization (A834P) and exonuclease
      (N408K) activities contributes to antiviral resistance and altered replication
      kinetics in these mutant strains. The identification of these multidrug-resistant
      CMV strains in at-risk seronegative recipients of organs from seropositive donors
      suggests that improved prophylactic and treatment strategies are required. The
      additive effect of multiple mutations on antiviral susceptibility suggests that
      increasing antiviral-resistant phenotypes can result from different virus
      antiviral interactions.

PMID- 17043129
TI  - Clonal spread of macrolide- and tetracycline-resistant [erm(A) tet(O)] emm77
      Streptococcus pyogenes isolates in Italy and Norway.

PMID- 17043130
TI  - LfrR is a repressor that regulates expression of the efflux pump LfrA in
      Mycobacterium smegmatis.
AB  - The lfrA gene of Mycobacterium smegmatis encodes an efflux pump which mediates
      resistance to different fluoroquinolones, cationic dyes, and anthracyclines. The
      deletion of the lfrR gene, coding for a putative repressor and localized upstream
      of lfrA, increased the lfrA expression. In this study, reverse transcription-PCR
      experiments showed that the two genes are organized as an operon, and lacZ
      reporter fusions were used to identify the lfrRA promoter region. The lfrRA
      promoter assignment was verified by mapping the transcription start site by
      primer extension. Furthermore, we found that some substrates of the multidrug
      transporter LfrA, e.g., acriflavine, ethidium bromide, and rhodamine 123, enhance
      lfrA expression at a detectable level of transcription. LfrR protein was purified
      from Escherichia coli as a fusion protein with a hexahistidine tag and found to
      bind specifically to a fragment 143 bp upstream of lfrR by gel shift analysis.
      Furthermore, acriflavine was able to cause the dissociation of the LfrR from the
      promoter, thus suggesting that this molecule interacts directly with LfrR,
      inducing lfrA expression. These results suggest that the LfrR repressor is able
      to bind to different compounds, which allows induction of LfrA multidrug efflux
      pump expression in response to these ones. Together, all data suggest that the
      LfrA pump is tightly regulated and that the repression and induction can be
      switched about a critical substrate concentration which is toxic for the cell.

PMID- 17043131
TI  - Contribution of target gene mutations and efflux to decreased susceptibility of
      Salmonella enterica serovar typhimurium to fluoroquinolones and other
      antimicrobials.
AB  - The mechanisms involved in fluoroquinolone resistance in Salmonella enterica
      include target alterations and overexpression of efflux pumps. The present study
      evaluated the role of known and putative multidrug resistance efflux pumps and
      mutations in topoisomerase genes among laboratory-selected and naturally
      occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium
      strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 microg/ml were
      derived in vitro using serovar Typhimurium S21. These mutants also showed
      decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials,
      including tetracycline, chloramphenicol, and several beta-lactams. The expression
      of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were
      substantially increased (>or=2-fold) among the fluoroquinolone-resistant mutants.
      Increased expression was also observed, but to a lesser extent, with three other
      putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with
      ciprofloxacin MICs of >or=32 microg/ml. Deletion of acrAB or tolC in S21 and its
      fluoroquinolone-resistant mutants resulted in increased susceptibility to
      fluoroquinolones and other tested antimicrobials. In naturally occurring
      fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC
      increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA
      double mutations (S83F D87N) with wild-type gyrA increased susceptibility>500
      fold. These results indicate that a combination of topoisomerase gene mutations,
      as well as enhanced antimicrobial efflux, plays a critical role in the
      development of fluoroquinolone resistance in both laboratory-derived and
      naturally occurring quinolone-resistant serovar Typhimurium strains.

PMID- 17043132
TI  - Cardiac perforation 6 weeks after percutaneous atrial septal defect repair using
      an Amplatzer septal occluder.
AB  - A 14-year-old boy presented to the emergency department unaccompanied by his
      parents with a decreased level of consciousness, bradycardia, and hypotension
      after a syncopal episode. The patient's electronic chart revealed a percutaneous
      closure of a secundum atrial septal defect using an Amplatzer septal occluder
      (AGA Medical, Golden Valley, MN) 6 weeks before this presentation. An urgent
      echocardiogram revealed a moderate pericardial effusion, and 320 mL of fresh
      blood was evacuated by subxiphoid pericardiocentesis. The child underwent
      surgical exploration and was found to have a perforation in the superior
      posterior aspect of the right atrium, which was corrected. The septal occluder
      was extracted, and the atrial septal defect was closed with a pericardial patch.
      This case illustrates a rare but life-threatening complication of percutaneous
      closure of atrial septal defect using an Amplatzer septal occluder and the
      importance of timely access to patient records when available history and
      physical examination are limited.

PMID- 17043134
TI  - Systemic hyalinosis: a distinctive early childhood-onset disorder characterized
      by mutations in the anthrax toxin receptor 2 gene (ANTRX2).
AB  - OBJECTIVE: We sought to further characterize the phenotype and facilitate
      clinical recognition of systemic hyalinosis in children who present with chronic
      pain and progressive contractures in early childhood. PATIENTS AND METHODS: We
      report on 3 children who presented in infancy with symptoms and signs that
      initially were not recognized to be those of systemic hyalinosis. Although the
      children were evaluated for a variety of problems, including lysosomal storage
      disorders and nonaccidental trauma, all eventually underwent genetic analysis of
      the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic
      hyalinosis. RESULTS: We describe the recognizable but variable clinical phenotype
      of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals
      presented in early infancy with severe pain and progressive contractures. Initial
      diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony
      prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of
      systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case.
      Although 2 of the children died in infancy as a result of complications of
      chronic diarrhea, the third child has survived into midchildhood. These data
      suggest that some ANTRX2 mutations, such as that identified in the long-term
      survivor, may be associated with a less severe course of disease. CONCLUSIONS:
      Although some aspects of systemic hyalinosis may resemble lysosomal storage
      disorders, the clinical features of systemic hyalinosis are distinctive, and
      detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of
      affected individuals should allow for aggressive pain control and expectant
      management of the multiple associated problems, including gastrointestinal
      dysfunction.

PMID- 17043133
TI  - Reducing premature infants' length of stay and improving parents' mental health
      outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal
      intensive care unit program: a randomized, controlled trial.
AB  - OBJECTIVE: Although low birth weight premature infants and parents are at high
      risk for adverse health outcomes, there is a paucity of studies that test early
      NICU interventions with parents to prevent the development of negative parent
      infant interaction trajectories and to reduce hospital length of stay. Our
      objective was to evaluate the efficacy of an educational-behavioral intervention
      program (ie, Creating Opportunities for Parent Empowerment) that was designed to
      enhance parent-infant interactions and parent mental health outcomes for the
      ultimate purpose of improving child developmental and behavior outcomes. DESIGN,
      SETTING, AND PARTICIPANTS: A randomized, controlled trial was conducted with 260
      families with preterm infants from 2001 to 2004 in 2 NICUs in the northeast
      United States. Parents completed self-administered instruments during
      hospitalization, within 7 days after infant discharge, and at 2 months' corrected
      age. Blinded observers rated parent-infant interactions in the NICU.
      INTERVENTION: All participants received 4 intervention sessions of audiotaped and
      written materials. Parents in the Creating Opportunities for Parent Empowerment
      program received information and behavioral activities about the appearance and
      behavioral characteristics of preterm infants and how best to parent them. The
      comparison intervention contained information regarding hospital services and
      policies. MAIN OUTCOME MEASURES: Parental stress, depression, anxiety, and
      beliefs; parent-infant interaction during the NICU stay; NICU length of stay; and
      total hospitalization were measured. RESULTS: Mothers in the Creating
      Opportunities for Parent Empowerment program reported significantly less stress
      in the NICU and less depression and anxiety at 2 months' corrected infant age
      than did comparison mothers. Blinded observers rated mothers and fathers in the
      Creating Opportunities for Parent Empowerment program as more positive in
      interactions with their infants. Mothers and fathers also reported stronger
      beliefs about their parental role and what behaviors and characteristics to
      expect of their infants during hospitalization. Infants in the Creating
      Opportunities for Parent Empowerment program had a 3.8-day shorter NICU length of
      stay (mean: 31.86 vs 35.63 days) and 3.9-day shorter total hospital length of
      stay (mean: 35.29 vs 39.19 days) than did comparison infants. CONCLUSIONS: A
      reproducible educational-behavioral intervention program for parents that
      commences early in the NICU can improve parent mental health outcomes, enhance
      parent-infant interaction, and reduce hospital length of stay.

PMID- 17043135
TI  - Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180
      to promote adhesion disassembly.
AB  - The regulated assembly and disassembly of focal adhesions and adherens junctions
      contributes to cell motility and tumor invasion. Pivotal in this process is
      phosphorylation of myosin light chain-2 (MLC2) by Rho kinase (ROCK) downstream of
      Rho activation, which generates the contractile force necessary to drive
      disassembly of epithelial cell-cell junctions and cell-matrix adhesions at the
      rear of migrating cells. How Rho-ROCK-MLC2 activation occurs at these distinct
      cellular locations is not known, but the emerging concept that endocytic dynamics
      can coordinate key intracellular signaling events provides vital clues. We report
      that endosomes containing the promigratory receptor Endo180 (CD280) can generate
      Rho-ROCK-MLC2-based contractile signals. Moreover, we provide evidence for a
      cellular mechanism in which Endo180-containing endosomes are spatially localized
      to facilitate their contractile signals directly at sites of adhesion turnover.
      We propose migration driven by Endo180 as a model for the spatial regulation of
      contractility and adhesion dynamics by endosomes.

PMID- 17043136
TI  - Protein tyrosine phosphatase TbPTP1: A molecular switch controlling life cycle
      differentiation in trypanosomes.
AB  - Differentiation in African trypanosomes (Trypanosoma brucei) entails passage
      between a mammalian host, where parasites exist as a proliferative slender form
      or a G0-arrested stumpy form, and the tsetse fly. Stumpy forms arise at the peak
      of each parasitaemia and are committed to differentiation to procyclic forms that
      inhabit the tsetse midgut. We have identified a protein tyrosine phosphatase
      (TbPTP1) that inhibits trypanosome differentiation. Consistent with a tyrosine
      phosphatase, recombinant TbPTP1 exhibits the anticipated substrate and inhibitor
      profile, and its activity is impaired by reversible oxidation. TbPTP1
      inactivation in monomorphic bloodstream trypanosomes by RNA interference or
      pharmacological inhibition triggers spontaneous differentiation to procyclic
      forms in a subset of committed cells. Consistent with this observation,
      homogeneous populations of stumpy forms synchronously differentiate to procyclic
      forms when tyrosine phosphatase activity is inhibited. Our data invoke a new
      model for trypanosome development in which differentiation to procyclic forms is
      prevented in the bloodstream by tyrosine dephosphorylation. It may be possible to
      use PTP1B inhibitors to block trypanosomatid transmission.

PMID- 17043137
TI  - Dynamic subcompartmentalization of the mitochondrial inner membrane.
AB  - The inner membrane of mitochondria is organized in two morphologically distinct
      domains, the inner boundary membrane (IBM) and the cristae membrane (CM), which
      are connected by narrow, tubular cristae junctions. The protein composition of
      these domains, their dynamics, and their biogenesis and maintenance are poorly
      understood at the molecular level. We have used quantitative immunoelectron
      microscopy to determine the distribution of a collection of representative
      proteins in yeast mitochondria belonging to seven major processes: oxidative
      phosphorylation, protein translocation, metabolite exchange, mitochondrial
      morphology, protein translation, iron-sulfur biogenesis, and protein degradation.
      We show that proteins are distributed in an uneven, yet not exclusive, manner
      between IBM and CM. The individual distributions reflect the physiological
      functions of proteins. Moreover, proteins can redistribute between the domains
      upon changes of the physiological state of the cell. Impairing assembly of
      complex III affects the distribution of partially assembled subunits. We propose
      a model for the generation of this dynamic subcompartmentalization of the
      mitochondrial inner membrane.

PMID- 17043138
TI  - SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the
      mammalian ER.
AB  - Protein quality control in the endoplasmic reticulum (ER) involves recognition of
      misfolded proteins and dislocation from the ER lumen into the cytosol, followed
      by proteasomal degradation. Viruses have co-opted this pathway to destroy
      proteins that are crucial for host defense. Examination of dislocation of class I
      major histocompatibility complex (MHC) heavy chains (HCs) catalyzed by the human
      cytomegalovirus (HCMV) immunoevasin US11 uncovered a conserved complex of the
      mammalian dislocation machinery. We analyze the contributions of a novel complex
      member, SEL1L, mammalian homologue of yHrd3p, to the dislocation process.
      Perturbation of SEL1L function discriminates between the dislocation pathways
      used by US11 and US2, which is a second HCMV protein that catalyzes dislocation
      of class I MHC HCs. Furthermore, reduction of the level of SEL1L by small hairpin
      RNA (shRNA) inhibits the degradation of a misfolded ribophorin fragment (RI332)
      independently of the presence of viral accessories. These results allow us to
      place SEL1L in the broader context of glycoprotein degradation, and imply the
      existence of multiple independent modes of extraction of misfolded substrates
      from the mammalian ER.

PMID- 17043139
TI  - Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.
AB  - A mutation in the small GTPase Rab38 gives rise to the mouse coat color phenotype
      "chocolate" (cht), implicating Rab38 in the regulation of melanogenesis. However,
      its role remains poorly characterized. We report that cht Rab38(G19V) is inactive
      and that the nearly normal pigmentation in cht melanocytes results from
      functional compensation by the closely related Rab32. In cht cells treated with
      Rab32-specific small interfering RNA, a dramatic loss of pigmentation is
      observed. In addition to mature melanosomes, Rab38 and Rab32 localize to
      perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1,
      consistent with a role in the intracellular sorting of these proteins. In
      Rab38/Rab32-deficient cells, tyrosinase appears to be mistargeted and degraded
      after exit from the trans-Golgi network (TGN). This suggests that Rab38 and Rab32
      regulate a critical step in the trafficking of melanogenic enzymes, in
      particular, tyrosinase, from the TGN to melanosomes. This work identifies a key
      role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of
      melanosomes and potentially other lysosome-related organelles.

PMID- 17043140
TI  - Membranes of the world unite!
AB  - Despite diverse origins, cellular fusion mechanisms converge at a pathway of
      phospholipid bilayer fusion. In this mini-review, we discuss how proteins can
      mediate each of the three major stages in the fusion pathway: contact,
      hemifusion, and the opening of an expanding fusion pore.

PMID- 17043141
TI  - Darkness descends with two Rabs.
AB  - Over 60 distinct Rab GTPases regulate specific vesicular transport steps in the
      mammalian central vacuolar system. Wasmeier et al. (this issue, p. 271) reveal a
      redundant role for two tissue-specific Rab proteins in regulating transport to a
      tissue-specific lysosome-related organelle, the melanosome.

PMID- 17043142
TI  - Growth control by EGF repeats of the C. elegans Fibulin-1C isoform.
AB  - Fibulin is a broadly conserved component of the extracellular matrix (ECM).
      Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1)
      controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J.
      Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki.
      2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel.
      2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also
      controls developmental growth and that one isoform of fibulin-1, called FBL-1C,
      controls both functions by distinct mechanisms. A large FBL-1C fragment,
      including both epidermal growth factor (EGF) and fibulin-type C domains, is
      responsible for constraining gonadal width, but a much smaller fragment
      containing only two complete EGF repeats (EGF1-2C+) is critical for developmental
      growth. We suggest that the larger fragment serves a scaffolding function to
      stabilize the basement membrane and that the smaller fragment provides a
      regulatory function at the cell surface or within the ECM to control growth.

PMID- 17043143
TI  - T cell receptor for antigen induces linker for activation of T cell-dependent
      activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2.
AB  - Adaptor proteins positively or negatively regulate the T cell receptor for
      antigen (TCR) signaling cascade. We report that after TCR stimulation, the
      inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are
      involved in a multimolecular complex including the lipid phosphatase Src homology
      2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP)-1 and Grb-2
      which interacts with the membrane signaling scaffold linker for activation of T
      cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored
      recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative
      control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the
      view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback
      loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a
      critical role in shaping the immune response and as gatekeepers for T cell
      tolerance.

PMID- 17043144
TI  - Triggering CD40 on endothelial cells contributes to tumor growth.
AB  - Inflammatory cells can either promote or inhibit tumor growth. Here we studied
      whether CD40, a key molecule for adaptive immune response, has any role in
      mammary carcinogenesis of BALB/NeuT transgenic tumor-prone mice. We transferred
      the HER2/neu oncogene into CD40-null background to obtain the CD40-KO/NeuT
      strain. CD40-KO/NeuT mice showed delayed tumor onset and reduced tumor
      multiplicity. BM (BM) transplantation experiments excluded a role of BM-derived
      cells in the reduced tumorigenicity associated with CD40 deficiency. Rather, CD40
      expressed by endothelial cells (ECs) takes part to the angiogenic process.
      Accordingly, large vessels, well organized around the tumor lobular structures,
      characterize BALB/NeuT tumors, whereas tiny numerous vessels with scarce
      extracellular matrix are dispersed in the parenchyma of poorly organized CD40
      KO/NeuT tumors. Activated platelets, which may interact with and activate ECs,
      are a possible source of CD40L. Their localization within tumor vessels prompted
      the idea of treating BALB/NeuT and CD40-KO/NeuT mice chronically with the anti
      platelet drug clopidogrel, known to inhibit platelet CD40L expression. Treatment
      of BALB/NeuT mice reduced tumor growth to a level similar to CD40-deficient mice,
      whereas CD40-KO/NeuT mice treated or not showed the same attenuated tumor
      outgrowth, indicating that activated platelets are the likely source of CD40L in
      this model. Collectively, these data point to a participation of CD40/CD40L in
      the angiogenic processes associated with mammary carcinogenesis of BALB/NeuT
      mice.

PMID- 17043145
TI  - Follicular lymphoma-like B cells in healthy individuals: a novel intermediate
      step in early lymphomagenesis.
AB  - Follicular lymphoma is one of the most common adult lymphoma, and remains
      virtually incurable despite its relatively indolent nature. t(14;18)(q32;q21)
      translocation, the genetic hallmark and early initiating event of follicular
      lymphoma (FL) pathogenesis, is also present at low frequency in the peripheral
      blood of healthy individuals. It has long been assumed that in healthy
      individuals t(14;18) is carried by circulating quiescent naive B cells, where its
      oncogenic potential would be restrained. Here, we question this current view and
      demonstrate that in healthy individuals, t(14;18) is actually carried by an
      expanding population of atypical B cells issued from germinal centers, displaying
      genotypic and phenotypic features of FL, and prone to constitute potent
      premalignant FL niches. These findings strongly impact both on the current
      understanding of disease progression and on the proper handling of t(14;18)
      frequency in blood as a potential early biomarker for lymphoma.

PMID- 17043146
TI  - Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative
      disease.
AB  - Though Abl inhibitors are often successful therapies for the initial stages of
      chronic myelogenous leukemia (CML), refractory cases highlight the need for novel
      molecular insights. We demonstrate that mice deficient in the enzyme 12/15
      lipoxygenase (12/15-LO) develop a myeloproliferative disorder (MPD) that
      progresses to transplantable leukemia. Although not associated with dysregulation
      of Abl, cells isolated from chronic stage 12/15-LO-deficient (Alox15) mice
      exhibit increased activation of the phosphatidylinositol 3-kinase (PI3-K)
      pathway, as indicated by enhanced phosphorylation of Akt. Furthermore, the
      transcription factor interferon consensus sequence binding protein (ICSBP) is
      hyperphosphorylated and displays decreased nuclear accumulation, translating into
      increased levels of expression of the oncoprotein Bcl-2. The ICSBP defect,
      exaggerated levels of Bcl-2, and prolonged leukemic cell survival associated with
      chronic stage Alox15 MPD are all reversible upon treatment with a PI3-K
      inhibitor. Remarkably, the evolution of Alox15 MPD to leukemia is associated with
      additional regulation of ICSBP on an RNA level, highlighting the potential
      usefulness of the Alox15 model for understanding the transition of CML to crisis.
      Finally, 12/15-LO expression suppresses the growth of a human CML-derived cell
      line. These data identify 12/15-LO as an important suppressor of MPD via its role
      as a critical upstream effector in the regulation of PI3-K-dependent ICSBP
      phosphorylation.

PMID- 17043147
TI  - Giving blood: a new role for CD40 in tumorigenesis.
AB  - CD40 was initially identified as a receptor expressed by B cells that is crucial
      for inducing an effective adaptive immune response. CD40 was subsequently shown
      to be expressed by endothelial cells and to promote angiogenesis. New data now
      show that in tumor-prone transgenic mice, CD40-mediated neovascularization is
      essential for early stage tumorigenicity. This suggests, at least in this mouse
      model, that CD40 has an important role in the angiogenic process that is coupled
      to carcinogenesis, a finding that could lead to novel therapeutic opportunities.

PMID- 17043148
TI  - Thermodynamics of CFTR channel gating: a spreading conformational change
      initiates an irreversible gating cycle.
AB  - CFTR is the only ABC (ATP-binding cassette) ATPase known to be an ion channel.
      Studies of CFTR channel function, feasible with single-molecule resolution,
      therefore provide a unique glimpse of ABC transporter mechanism. CFTR channel
      opening and closing (after regulatory-domain phosphorylation) follows an
      irreversible cycle, driven by ATP binding/hydrolysis at the nucleotide-binding
      domains (NBD1, NBD2). Recent work suggests that formation of an NBD1/NBD2 dimer
      drives channel opening, and disruption of the dimer after ATP hydrolysis drives
      closure, but how NBD events are translated into gate movements is unclear. To
      elucidate conformational properties of channels on their way to opening or
      closing, we performed non-equilibrium thermodynamic analysis. Human CFTR channel
      currents were recorded at temperatures from 15 to 35 degrees C in inside-out
      patches excised from Xenopus oocytes. Activation enthalpies(DeltaH(double
      dagger)) were determined from Eyring plots. DeltaH(double dagger) was 117 +/- 6
      and 69 +/- 4 kJ/mol, respectively, for opening and closure of partially
      phosphorylated, and 96 +/- 6 and 73 +/- 5 kJ/mol for opening and closure of
      highly phosphorylated wild-type (WT) channels. DeltaH(double dagger) for reversal
      of the channel opening step, estimated from closure of ATP hydrolysis-deficient
      NBD2 mutant K1250R and K1250A channels, and from unlocking of WT channels locked
      open with ATP+AMPPNP, was 43 +/- 2, 39 +/- 4, and 37 +/- 6 kJ/mol, respectively.
      Calculated upper estimates of activation free energies yielded minimum estimates
      of activation entropies (DeltaS(double dagger)), allowing reconstruction of the
      thermodynamic profile of gating, which was qualitatively similar for partially
      and highly phosphorylated CFTR. DeltaS(double dagger) appears large for opening
      but small for normal closure. The large DeltaH(double dagger) and DeltaS(double
      dagger) (TDeltaS(double dagger) >/= 41 kJ/mol) for opening suggest that the
      transition state is a strained channel molecule in which the NBDs have already
      dimerized, while the pore is still closed. The small DeltaS(double dagger) for
      normal closure is appropriate for cleavage of a single bond (ATP's beta-gamma
      phosphate bond), and suggests that this transition state does not require large
      scale protein motion and hence precedes rehydration (disruption) of the dimer
      interface.

PMID- 17043149
TI  - Cooperative gating between single HCN pacemaker channels.
AB  - HCN pacemaker channels (I(f), I(q), or I(h)) play a fundamental role in the
      physiology of many excitable cell types, including cardiac myocytes and central
      neurons. While cloned HCN channels have been studied extensively in macroscopic
      patch clamp experiments, their extremely small conductance has precluded single
      channel analysis to date. Nevertheless, there remain fundamental questions about
      HCN gating that can be resolved only at the single channel level. Here we present
      the first detailed single channel study of cloned mammalian HCN2. Excised patch
      clamp recordings revealed discrete hyperpolarization-activated, cAMP-sensitive
      channel openings with amplitudes of 150-230 fA in the activation voltage range.
      The average conductance of these openings was approximately 1.5 pS at -120 mV in
      symmetrical 160 mM K(+). Some traces with multiple channels showed unusual gating
      behavior, characterized by a variable long delay after a voltage step followed by
      runs of openings. Noise analysis on macroscopic currents revealed fluctuations
      whose magnitudes were systematically larger than predicted from the actual single
      channel current size, consistent with cooperativity between single HCN channels.

PMID- 17043150
TI  - Detection of the opening of the bundle crossing in KcsA with fluorescence
      lifetime spectroscopy reveals the existence of two gates for ion conduction.
AB  - The closed KcsA channel structure revealed a crossing of the cytosolic ends of
      the transmembrane helices blocking the permeation pathway. It is generally agreed
      that during channel opening this helical bundle crossing has to widen in order to
      enable access to the inner cavity. Here, we address the question of whether the
      opening of the inner gate is sufficient for ion conduction, or if a second gate,
      located elsewhere, may interrupt the ion flow. We used fluorescence lifetime
      measurements on KcsA channels labeled with tetramethylrhodamine at residues in
      the C-terminal end of TM2 to report on the opening of the lower pore region. We
      found two populations of channels with different fluorescence lifetimes, whose
      relative distribution agrees with the open probability of the channel. The
      absolute fraction of channels found with an open bundle crossing is too high to
      explain the low open probability of the KcsA-WT channel. We found the same
      distribution as in the WT channel between open and closed bundle crossing for two
      KcsA mutants, A73E and E71A, which significantly increase open probability at low
      pH. These two results strongly suggest that a second gate in the ion permeation
      pathway exists. The location of the mutations A73E and E71A suggests that the
      second gate may be the selectivity filter, which resides in an inactivated state
      under steady-state conditions. Since the long closed times observed in KcsA-WT
      are not present in KcsA-A73E or -E71A, we propose that KcsA-WT remains
      predominantly in a state with an open bundle crossing but closed (inactivated)
      second gate, while the mutations A73E and E71A sharply decrease the tendency to
      enter in the inactivated state, and as a consequence, the second gate is
      predominantly open at steady state. The ability to monitor the opening of the
      bundle crossing optically enables the direct recording of the movement of the
      pore helices while the channel is functioning.

PMID- 17043151
TI  - Cross talk between activation and slow inactivation gates of Shaker potassium
      channels.
AB  - This study addresses the energetic coupling between the activation and slow
      inactivation gates of Shaker potassium channels. To track the status of the
      activation gate in inactivated channels that are nonconducting, we used two
      functional assays: the accessibility of a cysteine residue engineered into the
      protein lining the pore cavity (V474C) and the liberation by depolarization of a
      Cs(+) ion trapped behind the closed activation gate. We determined that the rate
      of activation gate movement depends on the state of the inactivation gate. A
      closed inactivation gate favors faster opening and slower closing of the
      activation gate. We also show that hyperpolarization closes the activation gate
      long before a channel recovers from inactivation. Because activation and slow
      inactivation are ubiquitous gating processes in potassium channels, the cross
      talk between them is likely to be a fundamental factor in controlling ion flux
      across membranes.

PMID- 17043152
TI  - Positive charges at the intracellular mouth of the pore regulate anion conduction
      in the CFTR chloride channel.
AB  - Many different ion channel pores are thought to have charged amino acid residues
      clustered around their entrances. The so-called surface charges contributed by
      these residues can play important roles in attracting oppositely charged ions
      from the bulk solution on one side of the membrane, increasing effective local
      counterion concentration and favoring rapid ion movement through the channel.
      Here we use site-directed mutagenesis to identify arginine residues contributing
      important surface charges in the intracellular mouth of the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl(-) channel pore. While wild-type
      CFTR was associated with a linear current-voltage relationship with symmetrical
      solutions, strong outward rectification was observed after mutagenesis of two
      arginine residues (R303 and R352) located near the intracellular ends of the
      fifth and sixth transmembrane regions. Current rectification was dependent on the
      charge present at these positions, consistent with an electrostatic effect.
      Furthermore, mutagenesis-induced rectification was more pronounced at lower Cl(-)
      concentrations, suggesting that these mutants had a reduced ability to
      concentrate Cl(-) ions near the inner pore mouth. R303 and R352 mutants exhibited
      reduced single channel conductance, especially at negative membrane potentials,
      that was dependent on the charge of the amino acid residue present at these
      positions. However, the very low conductance of both R303E and R352E-CFTR could
      be greatly increased by elevating intracellular Cl(-) concentration. Modification
      of an introduced cysteine residue at position 303 by charged methanethiosulfonate
      reagents reproduced charge-dependent effects on current rectification.
      Mutagenesis of arginine residues in the second and tenth transmembrane regions
      also altered channel permeation properties, however these effects were not
      consistent with changes in channel surface charges. These results suggest that
      positively charged arginine residues act to concentrate Cl(-) ions at the inner
      mouth of the CFTR pore, and that this contributes to maximization of the rate of
      Cl(-) ion permeation through the pore.

PMID- 17043154
TI  - Concentration-dependent mode of interaction of angiotensin II receptor blockers
      with uric acid transporter.
AB  - Serum uric acid (SUA) is currently recognized as a risk factor for cardiovascular
      disease. It has been reported that an angiotensin II receptor blocker (ARB),
      losartan, decreases SUA level, whereas other ARBs, such as candesartan, have no
      lowering effect. Because the renal uric acid transporter (URAT1) is an important
      factor controlling the SUA level, we examined the involvement of URAT1 in those
      differential effects of various ARBs on SUA level at clinically relevant
      concentrations. This study was done by using URAT1-expressing Xenopus oocytes.
      Losartan, pratosartan, and telmisartan exhibited cis-inhibitory effects on the
      uptake of uric acid by URAT1, whereas at higher concentrations, only telmisartan
      did, and these ARBs reduced the uptake in competitive inhibition kinetics. On the
      other hand, candesartan, EXP3174 [2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5
      yl)biphenyl-4-yI)methyl]imidazole-5-carboxylic acid] (a major metabolite of
      losartan), olmesartan, and valsartan were not inhibitory. Preloading of those
      ARBs in the oocytes enhanced the URAT1-mediated uric acid uptake, showing a trans
      stimulatory effect. The present study is a first demonstration of the
      differential effects of ARBs on URAT1 that some ARBs are both cis-inhibitory and
      trans-stimulatory, depending on concentration, whereas others exhibit either a
      trans-stimulatory or cis-inhibitory effect alone, which could explain the
      clinically observed differential effects of ARBs on SUA level. Furthermore, it
      was found that such differential effects of ARBs on URAT1 could be predicted from
      the partial chemical structures of ARBs, which will be useful information for the
      appropriate use and development of ARBs without an increase of SUA.

PMID- 17043155
TI  - Valproic acid is not a substrate for P-glycoprotein or multidrug resistance
      proteins 1 and 2 in a number of in vitro and in vivo transport assays.
AB  - The antiepileptic drug valproic acid (VPA) is widely used in the treatment of
      epilepsy, bipolar disorders, and migraine. However, rather high doses are
      required for the clinical effects of VPA, which is due to its relatively
      inefficient delivery to the brain. The poor brain distribution of VPA is thought
      to reflect an asymmetric transport system at the blood-brain barrier (BBB). Based
      on recent data from in vitro experiments, multidrug resistance proteins (MRPs)
      have been proposed to be involved in the efflux transport of VPA at the BBB. In
      the present study, we used different experimental in vitro and in vivo strategies
      to evaluate whether VPA is a substrate for MRPs or the efflux transporter P
      glycoprotein (Pgp). In contrast to known Pgp or MRP substrates, such as
      cyclosporin A or vinblastine, no directional transport of VPA was observed in
      cell monolayer efflux assays using the kidney cell lines Madin Darby canine
      kidney II and LLC-PK1, which had been transfected with either human or mouse
      cDNAs for the genes encoding Pgp, MRP1, or MRP2. Likewise, no indication for
      efflux transport of VPA was obtained in a rat microdialysis model, using
      inhibitors of either Pgp or MRPs. Furthermore, a significant role of MRP2 in
      brain efflux of VPA was excluded by using MRP2-deficient rats. Our data do not
      support the hypothesis that MRP1 or MRP2 is involved in the efflux of VPA from
      the brain. Thus, the molecular identity of the putative transporter(s) mediating
      the active efflux of VPA from the brain remains to be elucidated.

PMID- 17043156
TI  - Atrial peptides modify the effect of marinobufagenin on sodium pumps:
      implications for blood pressure control.

PMID- 17043158
TI  - ANP differentially modulates marinobufagenin-induced sodium pump inhibition in
      kidney and aorta.
AB  - NaCl loading and plasma volume expansion stimulate 2 natriuretic systems,
      vasoconstrictor, digitalis-like Na/K-ATPase inhibitors and vasorelaxant ANP
      peptides. Several hormones, including ANP, regulate activity of the Na/K-ATPase
      by modulation of its phosphorylation state. We studied effects of ANP on Na/K
      ATPase phosphorylation and inhibition by an endogenous sodium pump ligand,
      marinobufagenin, in the aorta and renal medulla from male Sprague-Dawley rats.
      Marinobufagenin dose-dependently inhibited the Na/K-ATPase in renal and vascular
      membranes at the level of higher (nanomolar) and lower affinity (micromolar)
      binding sites. Marinobufagenin (1 nmol/L) inhibited Na/K-ATPase in aortic
      sarcolemma (18%) and in renal medulla (19%). prepro-ANP 104 to 123 (ppANP) and
      alpha-human ANP ([alpha-hANP] both 1 nmol/L) potentiated marinobufagenin-induced
      Na/K-ATPase inhibition in the kidney, but reversed the effect of marinobufagenin
      in the aorta. Similarly, ppANP and alpha-hANP modulated the sodium pump (ouabain
      sensitive (86)Rb uptake) inhibitory effects of marinobufagenin in the aorta and
      renal medulla. In renal medulla, ppANP and alpha-hANP induced alpha-1 Na/K-ATPase
      phosphorylation, whereas in aorta, both peptides dephosphorylated Na/K-ATPase.
      The effect of ppANP on Na/K-ATPase phosphorylation and inhibition was mimicked by
      a protein kinase G activator, 8-Br-PET-cGMP (10 micromol/L), and prevented by a
      protein kinase G inhibitor, KT5823 (60 nmol/L). Our results suggest that alpha-1
      Na/K-ATPase inhibition by marinobufagenin in the kidney is enhanced via Na/K
      ATPase phosphorylation by ANP, whereas in the aorta, ANP exerts an opposite
      effect. The concurrent production of a vasorelaxant, ANP, and a vasoconstrictor,
      marinobufagenin, potentiate each other's natriuretic effects, but ANP peptides
      may offset the deleterious vasoconstrictor effect of marinobufagenin.

PMID- 17043157
TI  - Angiotensin II induces interleukin-6 in humans through a mineralocorticoid
      receptor-dependent mechanism.
AB  - This study tested the hypothesis that angiotensin promotes oxidative stress and
      inflammation in humans via aldosterone and the mineralocorticoid receptor. We
      measured the effect of intravenous aldosterone (0.7 mug/kg per hour for 10 hours
      followed by 0.9 mug/kg per hour for 4 hours) and vehicle in a randomized, double
      blind crossover study in 11 sodium-restricted normotensive subjects. Aldosterone
      increased interleukin (IL)-6 (from 4.7+/-4.9 to 9.4+/-7.1 pg/mL; F=4.94; P=0.04)
      but did not affect blood pressure, serum potassium, or high-sensitivity C
      reactive protein. We next conducted a randomized, double-blind, placebo
      controlled, crossover study to measure the effect of 3-hour infusion of
      angiotensin II (2 ng/kg per minute) and norepinephrine (30 ng/kg per minute) on
      separate days after 2 weeks of placebo or spironolactone (50 mg per day) in 14
      salt-replete normotensive subjects. Angiotensin II increased blood pressure
      (increase in systolic pressure: 13.7+/-7.5 and 15.2+/-9.4 mm Hg during placebo
      and spironolactone, respectively; P<0.001 for angiotensin II) and decreased renal
      plasma flow (-202+/-73 and -167+/-112 mL/min/1.73 kg/m(2); P<0.001 for
      angiotensin II effect) similarly during placebo and spironolactone.
      Spironolactone enhanced the aldosterone response to angiotensin II (increase of
      17.0+/-10.6 versus 9.0+/-5.7 ng/dL; P=0.002). Angiotensin II transiently
      increased free plasma F(2)-isoprostanes similarly during placebo and
      spironolactone. Angiotensin II increased serum IL-6 concentrations during placebo
      (from 1.8+/-1.1 to 2.4+/-1.4 pg/mL; F=4.5; P=0.04) but spironolactone prevented
      this effect (F=6.4; P=0.03 for spironolactone effect). Norepinephrine increased
      blood pressure and F(2)-isoprostanes but not aldosterone or IL-6. Aldosterone
      increases IL-6 in humans. These data suggest that angiotensin II induces IL-6
      through a mineralocorticoid receptor-dependent mechanism in humans. In contrast,
      angiotensin II-induced oxidative stress, as measured by F(2)-isoprostanes, is
      mineralocorticoid receptor independent and may be pressor dependent.

PMID- 17043160
TI  - Correlating ambulatory blood pressure measurements with arterial stiffness: a
      conceptual inconsistency?

PMID- 17043161
TI  - Cardiovascular effects of nonproteolytic activation of prorenin.

PMID- 17043162
TI  - Exaggerated cardiovascular stress responses and impaired beta-adrenergic-mediated
      pressor recovery in obese Zucker rats.
AB  - Clinical studies have demonstrated that the pressor response to acute stress is
      larger in obese versus lean individuals. We therefore tested the hypotheses that
      the pressor response to behavioral stress is greater in obese (OZRs) versus lean
      Zucker rats (LZRs) and that reduced beta-adrenergic-mediated vasodilation
      contributes to the enhanced pressor response. Animals were restrained and
      subjected to acute pulsatile air jet stress (3 minutes), followed by a poststress
      period of 20 minutes; beta-adrenergic blockade was achieved with propranolol (5
      mg/kg, IV) given 15 minutes before the start of air jet stress. Mean arterial
      pressure (MAP) was continuously monitored by telemetry. Untreated OZRs responded
      with a greater integrated pressor response (area under the curve [AUC]) to acute
      stress (41.2+/-6.1 versus 21.2+/-3.3 mm Hgx3 minutes, OZR versus LZR; P<0.05) and
      significantly reduced poststress recovery of MAP. Beta-adrenergic blockade had no
      effect on stress AUC in either LZRs or OZRs but significantly attenuated the
      poststress recovery of MAP in LZRs only (poststress AUC: -100.1+/-48.1 versus
      49.0+/-13.5 mm Hgx20 minutes, untreated versus propranolol; P<0.05). In
      anesthetized animals, significantly smaller increases in mesenteric vascular
      conductance contributed to blunted depressor responses to isoproterenol in OZRs
      versus LZRs, suggesting that beta-adrenergic stimulation causes a greater
      reduction in total peripheral resistance in lean versus obese animals. We
      conclude that beta-adrenergic-mediated vasodilation facilitates blood pressure
      recovery after stress and that this pathway is compromised in an animal model of
      morbid obesity, resulting in the impaired ability to regulate blood pressure
      during stress.

PMID- 17043163
TI  - CuZn superoxide dismutase deficiency: culprit of accelerated vascular aging
      process.

PMID- 17043164
TI  - Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype
      with aging.
AB  - The goal of this study was to test the hypothesis that loss of a single copy of
      the gene for CuZn superoxide dismutase (CuZnSOD) increases vascular superoxide
      levels and produces vascular dysfunction with aging. Responses of carotid
      arteries from young (7 months) and old (22 to 24 months of age) heterozygous
      CuZnSOD-deficient (CuZnSOD(+/-)) mice and their wild-type (CuZnSOD(+/+))
      littermates were examined in vitro. Total superoxide dismutase activity in aorta
      was reduced by approximately 30% (P<0.05) in CuZnSOD(+/-) mice compared with wild
      type mice. Responses to acetylcholine (an endothelium-dependent agonist) produced
      relaxation that was similar (P>0.05) in carotid arteries from young wild-type,
      young CuZnSOD(+/-), and old wild-type mice. In contrast, relaxation to
      acetylcholine was markedly impaired in old CuZnSOD(+/-) mice (eg, 100 micromol/L
      acetylcholine produced 51+/-5% and 96+/-5% relaxation in vessels from old
      CuZnSOD(+/-) and old wild-type mice, respectively). This effect was selective,
      because relaxation to nitroprusside (an endothelium-independent agonist) was not
      affected by either CuZnSOD genotype or aging. The impaired response to
      acetylcholine in old CuZnSOD(+/-) mice was restored toward normal with either
      tempol (a scavenger of superoxide; 1 mmol/L) or PJ34 (an inhibitor of poly-ADP
      ribose polymerase; 3 micromol/L). Vascular superoxide levels were increased in
      aorta in old CuZnSOD(+/+) mice and increased further in CuZnSOD(+/-) mice with
      aging. These findings provide the first direct evidence that normal CuZnSOD
      expression protects endothelial function and that deficiency in a single copy of
      the gene that encodes CuZnSOD produces increases in superoxide and marked
      impairment of endothelial function with aging.

PMID- 17043166
TI  - Activation of the cardiac proteasome during pressure overload promotes
      ventricular hypertrophy.
AB  - BACKGROUND: The adaptation of cardiac mass to hemodynamic overload requires an
      adaptation of protein turnover, ie, the balance between protein synthesis and
      degradation. We tested 2 hypotheses: (1) chronic left ventricular hypertrophy
      (LVH) activates the proteasome system of protein degradation, especially in the
      myocardium submitted to the highest wall stress, ie, the subendocardium, and (2)
      the proteasome system is required for the development of LVH. METHODS AND
      RESULTS: Gene and protein expression of proteasome subunits and proteasome
      activity were measured separately from left ventricular subendocardium and
      subepicardium, right ventricle, and peripheral tissues in a canine model of
      severe, chronic (2 years) LVH induced by aortic banding and then were compared
      with controls. Both gene and protein expressions of proteasome subunits were
      increased in LVH versus control (P<0.05), which was accompanied by a significant
      (P<0.05) increase in proteasome activity. Posttranslational modification of the
      proteasome was also detected by 2-dimensional gel electrophoresis. These changes
      were found specifically in left ventricular subendocardium but not in left
      ventricular subepicardium, right ventricle, or noncardiac tissues from the same
      animals. In a mouse model of chronic pressure overload, a 50% increase in heart
      mass and a 2-fold increase in proteasome activity (both P<0.05 versus sham) were
      induced. In that model, the proteasome inhibitor epoxomicin completely prevented
      LVH while blocking proteasome activation. CONCLUSIONS: The increase in proteasome
      expression and activity found during chronic pressure overload in myocardium
      submitted to higher stress is also required for the establishment of LVH.

PMID- 17043167
TI  - Long-term stimulation of adenosine A2b receptors begun after myocardial
      infarction prevents cardiac remodeling in rats.
AB  - BACKGROUND: Adenosine inhibits proliferation of cardiac fibroblasts and
      hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac
      remodeling. In the present study, we investigated whether chronic stimulation of
      adenosine receptors begun after myocardial infarction (MI) prevents cardiac
      remodeling. METHODS AND RESULTS: MI was produced in Wistar rats by permanent
      ligation of the left anterior descending coronary artery. One week after the
      onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP;
      the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable
      analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective
      adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective
      antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after
      treatment, hemodynamic and echocardiographic parameters in the DIP and CADO
      groups were significantly improved compared with the vehicle group. These
      hemodynamic and echocardiographic improvements were blunted by either 8-SPT or
      the selective adenosine A2b antagonist MRS1754 but not by the selective
      antagonists for other subtypes of adenosine receptors. The collagen volume
      fraction was smaller, and gene expression of the molecules associated with
      cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was
      reduced in the DIP and CADO groups compared with the vehicle group, both of which
      were attenuated by either 8-SPT or MRS1754. CONCLUSIONS: Long-term stimulation of
      adenosine A2b receptors begun after MI attenuates cardiac fibrosis in the
      noninfarcted myocardium and improves cardiac function. Drugs that stimulate
      adenosine A2b receptors or increase adenosine levels are new candidates for
      preventing cardiac remodeling after MI.

PMID- 17043168
TI  - Transcriptional profiling in coronary artery disease: indications for novel
      markers of coronary collateralization.
AB  - BACKGROUND: The development of collateral circulation plays an important role in
      protecting tissues from ischemic damage, and its stimulation has emerged as one
      of principal approaches to therapeutic angiogenesis. Clinical observations have
      documented substantial differences in the extent of collateralization among
      patients with coronary artery disease (CAD), with some individuals demonstrating
      marked abundance and others showing nearly complete absence of these vessels.
      Recent studies have suggested that circulating monocytes play a major role in
      collateral growth. The present study was undertaken to determine transcriptional
      profiles of circulating monocytes in CAD patients with different extents of
      collateral growth. METHODS AND RESULTS: Monocyte transcriptomes from CAD patients
      with and without collateral vessels were obtained by use of high-throughput
      expression profiling. Using a newly developed redundancy-based data mining
      method, we have identified a set of molecular markers characteristic of a
      "noncollateralgenic" phenotype. Moreover, we show that these transcriptional
      abnormalities are independent of the severity of CAD or any other known clinical
      parameter thought to affect collateral development and correlated with protein
      expression levels in monocytes and plasma. CONCLUSIONS: Monocyte transcription
      profiling identifies sets of patients with extensive versus poorly developed
      collateral circulation. Thus, genetic factors may heavily influence coronary
      collateral vessel growth in CAD and affect prognosis and response to therapeutic
      interventions.

PMID- 17043169
TI  - Short-term treatment with anti-CD3 antibody reduces the development and
      progression of atherosclerosis in mice.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease of the large
      arteries that is the primary cause of heart disease and stroke. Anti-CD3-specific
      antibodies suppress immune responses by antigenic modulation of the CD3
      antibody/T-cell receptor complex. Their unique capacity to restore self-tolerance
      in a mouse model of diabetes and, importantly, in patients with recent-onset type
      1 diabetes involves transforming growth factor-beta-dependent mechanisms via
      expansion and/or activation of regulatory T cells. We hypothesized that treatment
      with anti-CD3-specific antibodies might inhibit atherosclerosis development and
      progression in mice. METHODS AND RESULTS: Low-density lipoprotein receptor
      deficient mice were fed a high-cholesterol diet for 13 or 24 weeks. Anti-CD3
      antibody was administered on 5 consecutive days beginning 1 week before or 13
      weeks after the high-cholesterol diet was initiated, respectively. Control mice
      were injected in parallel with phosphate-buffered saline. Anti-CD3 antibody
      therapy reduced plaque development when administered before a high-cholesterol
      diet and markedly decreased lesion progression in mice with already established
      atherosclerosis. We found increased production of the antiinflammatory cytokine
      transforming growth factor-beta in concanavalin A-stimulated lymph node cells and
      enhanced expression of the regulatory T-cell marker Foxp3 in spleens of anti-CD3
      antibody-treated mice. A higher percentage of apoptotic cells within the plaques
      of anti-CD3 antibody-treated mice was also observed. CONCLUSIONS: Altered disease
      progression, combined with the emergence of this particular cytokine pattern,
      indicates that short-term treatment with an anti-CD3 antibody induces a
      regulatory T-cell phenotype that restores self-tolerance in a mouse model of
      atherosclerosis.

PMID- 17043170
TI  - Images in cardiovascular medicine. Bilateral sinus of Valsalva aneurysms: an
      extreme case.

PMID- 17043171
TI  - Images in cardiovascular medicine. Takayasu's arteritis: the "macaroni sign".

PMID- 17043172
TI  - Images in cardiovascular medicine. Vieussens' ring: combining computed tomography
      coronary angiography and magnetic resonance imaging in assessing collateral
      pathways.

PMID- 17043173
TI  - Letter by Undas and Jakubowski regarding article, "Relationship between
      homocysteine and mortality in chronic kidney disease".

PMID- 17043174
TI  - A view from Cyprus.

PMID- 17043175
TI  - Transvenous radiofrequency catheter ablation for atrial flutter and atrial
      fibrillation: the end of the beginning?

PMID- 17043176
TI  - Cardiac troponin: friend of the cardiac physician, foe to the cardiac patient?

PMID- 17043177
TI  - Are drug-eluting stents cost-effective? It depends on whom you ask.

PMID- 17043178
TI  - Drug-eluting stents: the price is not right.

PMID- 17043179
TI  - A new terminology for left ventricular walls and location of myocardial infarcts
      that present Q wave based on the standard of cardiac magnetic resonance imaging:
      a statement for healthcare professionals from a committee appointed by the
      International Society for Holter and Noninvasive Electrocardiography.

PMID- 17043180
TI  - Successful treatment of mucous membrane pemphigoid with infliximab.

PMID- 17043181
TI  - Aesthetic and functional efficacy of subcuticular running epidermal closures of
      the trunk and extremity: a rater-blinded randomized control trial.
AB  - OBJECTIVE: To ascertain whether subcuticular epidermal closures of elliptical
      excisions of the trunk and extremities result in better functional and cosmetic
      outcomes than simple running epidermal closures of the same sites. DESIGN:
      Randomized controlled trial, with allocation of epidermal closure of elliptical
      excisions to 4 arms, including 1 control arm (simple running polypropylene
      sutures removed after 14 days) and 3 experimental arms (subcuticular running
      polypropylene sutures removed after 14 days, subcuticular running polypropylene
      sutures left in place, and subcuticular running polyglactin 910 sutures left in
      place). All experimental interventions were preceded by deep dermal closure with
      simple interrupted polyglactin 910 sutures. Interventions were delivered by 3
      surgeons, who underwent 2 training sessions to minimize intersurgeon technique
      variability. SETTING: Institutional referral practice providing ambulatory care
      in an urban environment. PATIENTS: A consecutive sample of 36 adult patients
      (ages 18-65 years), each referred for concurrent elliptical excision of at least
      2 clinically atypical nevi of the trunk and/or extremity, were included in the
      study. MAIN OUTCOME MEASURES: Primary outcome measures obtained at 3 and 9 months
      included scar width in millimeters and blinded observer ordinal scale assessment
      of overall scar appearance. Secondary outcome measures included ratings on the
      standardized Vancouver Scar Scale and the Hollander Scar Scale; an additional
      nonstandard item was added to assess pruritus. RESULTS: No difference among
      groups was found in scar width at 3 or 9 months. Differences among groups were
      detected in overall scar appearance (3 months, P<.001; 9 months, P<.001),
      vascularity (3 months, P = .001; 9 months, P<.001), excessive distortion (3
      months, P = .04; 9 months, P = .02), contour irregularity (3 months, P<.001), and
      edge inversion (3 months, P = .01). The best overall appearance was with a
      subcuticular running polyglactin 910 suture left in place, and the next best was
      with a subcuticular running polypropylene suture left in place; differences
      across groups persisted but decreased in intensity at 9 months. A secondary
      analysis that matched high-tension anatomic sites (back and lower leg), and high
      and moderate tension sites (also chest and shoulder) yielded the same main
      effects and mostly the same results in pairwise comparisons. CONCLUSION: While
      scar width does not appear to vary significantly based on choice of epidermal
      closure, bilayered closures of the trunk and extremity have better overall
      appearance and less associated erythema at 3 and 9 months after surgery with the
      use of a subcuticular running polyglactin 910 suture left in place.

PMID- 17043182
TI  - Factors influencing coexistence of toenail onychomycosis with tinea pedis and
      other dermatomycoses: a survey of 2761 patients.
AB  - OBJECTIVE: To evaluate the prevalence and factors influencing the presence of
      concomitant dermatomycoses in patients with toenail onychomycosis. DESIGN:
      Prospective study based on a specially designed questionnaire completed by
      dermatologists. PATIENTS: A total of 2761 patients with toenail onychomycosis.
      MAIN OUTCOME MEASURES: The diagnosis of fungal skin infections was confirmed by
      direct microscopic examination or by culture. RESULTS: In 1181 patients (42.8%)
      with toenail onychomycosis, concomitant fungal skin infections were noted. Tinea
      pedis was the most common and was found in 933 patients (33.8%). Other
      concomitant fungal skin infections were fingernail onychomycosis (7.4%), tinea
      cruris (4.2%), tinea corporis (2.1%), tinea manuum (1.6%), and tinea capitis
      (0.5%). The presence of concomitant fungal skin infections depended on number of
      involved toenails; duration of onychomycosis; sex, age, and education level; area
      of residence; and type of isolated fungus. CONCLUSIONS: The coexistence of
      toenail onychomycosis with other types of fungal skin infections is a frequent
      phenomenon. It could be hypothesized that infected toenails may be a site from
      which the fungal infections could spread to other body areas. Effective therapy
      for onychomycosis might therefore be essential not only to treat the lesional
      toenails but also to prevent spreading the infection to other sites of the skin.

PMID- 17043183
TI  - Skin and soft tissue infections due to rapidly growing mycobacteria: comparison
      of clinical features, treatment, and susceptibility.
AB  - OBJECTIVE: To compare the demographics, clinical features, susceptibility
      patterns, and treatment for skin and soft tissue infections due to Mycobacterium
      fortuitum and Mycobacterium chelonae or Mycobacterium abscessus. DESIGN:
      Retrospective medical record review. SETTING: Mayo Clinic, Rochester, Minn.
      PATIENTS: All patients seen at our institution with a positive culture for M
      chelonae, M abscessus, or M fortuitum from skin or soft tissue sources between
      January 1, 1987, and October 31, 2004. MAIN OUTCOME MEASURES: Patient
      demographics, clinical characteristics, therapeutic data, microbiological data,
      and outcomes. RESULTS: The medical records of 63 patients with skin or soft
      tissue infections due to rapidly growing mycobacteria were reviewed. Patients
      with M chelonae or M abscessus were older (61.5 vs 45.9 years, P<.001) and more
      likely to be taking immunosuppressive medications (60% vs 17%, P = .002) than
      patients with M fortuitum. Mycobacterium fortuitum tended to manifest as a single
      lesion (89% vs 38%, P<.001), while most M chelonae or M abscessus manifested as
      multiple lesions (62% vs 11%, P<.001). More patients with M fortuitum had a prior
      invasive surgical procedure at the infected site (56% vs 27%, P = .04). Patients
      with multiple lesions were more likely to be taking immunosuppressive medications
      than those with single lesions (67% vs 30%, P = .006). Seven patients failed
      treatment, several of whom were immunocompromised and had multiple comorbidities.
      CONCLUSIONS: Skin and soft tissue infections due to rapidly growing mycobacteria
      are associated with systemic comorbidities, including the use of
      immunosuppressive medications. There are significant differences in the
      demographic and clinical features of patients who acquire specific organisms,
      including association with immunosuppression and surgical procedures.

PMID- 17043184
TI  - Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple
      myeloma.
AB  - OBJECTIVES: To examine dermatologic adverse effects of lenalidomide in patients
      with amyloidosis and multiple myeloma and to determine whether the adverse
      effects are different when lenalidomide is used alone compared with when it is
      used in combination with dexamethasone. DESIGN: Retrospective review of medical
      records. SETTING: Tertiary referral center. PATIENTS: Seventy-five patients with
      multiple myeloma and 23 patients with amyloidosis participating in clinical
      trials. INTERVENTION: In the 75 patients with multiple myeloma, lenalidomide was
      the treatment in 24 and lenalidomide and dexamethasone in 51. In the 23 patients
      with amyloidosis, lenalidomide was used alone. MAIN OUTCOME MEASURES: The
      frequency, type, severity, and time of onset of all skin eruptions that were
      temporally related to lenalidomide treatment were recorded. RESULTS: In the
      patients with amyloidosis treated with lenalidomide, 10 (43%) had rashes. In the
      patients with multiple myeloma, rashes occurred in 7 (29%) of those receiving
      lenalidomide alone and in 15 (29%) of those receiving lenalidomide and
      dexamethasone. The rashes were characterized as morbilliform, urticarial,
      dermatitic, acneiform, and undefined. Severe rashes required permanent
      discontinuation of lenalidomide therapy in 2 patients. In 23 patients (72%),
      rashes occurred in the first month after therapy was initiated; however, delayed
      onset rashes occurred in 9 (28%). CONCLUSIONS: The prevalence of dermatologic
      adverse effects in patients receiving lenalidomide was higher in those with
      amyloidosis than in those with multiple myeloma. The prevalence of skin eruptions
      was not diminished by the concurrent use of systemic corticosteroids. Most skin
      eruptions were mild and did not necessitate withdrawal of lenalidomide therapy.

PMID- 17043185
TI  - Validity of beachgoers' self-report of their sun habits.
AB  - OBJECTIVE: To examine the validity of beachgoers' self-reported sun protection
      and UV exposure using objective measures. DESIGN: Eighty-eight participants
      completed a brief survey when they arrived at the beach; their skin was swabbed
      for the presence of sunscreen, while an observer recorded their clothing worn to
      the beach and the presence of sunburn. On leaving the beach, an exit survey
      detailing activities and sun habits while on the beach was completed by the
      participants, follow-up sunscreen swabs were obtained, and sunburns were
      recorded. Clothing observations were made for a subgroup (n = 25) of participants
      during their beach stay. RESULTS: Most participants (38 [44%]) reported spending
      2 to 3 hours at the beach, which was consistent with researcher observations
      (Spearman rank correlation, r = 0.75). Moderate to substantial agreement was
      achieved between reported use of sunscreen for the day and sunscreen swabs
      (kappa, 0.54, 0.70, and 0.72 for the face, legs, and arms, respectively).
      Participants' self-report of clothing worn to the beach had substantial agreement
      with researcher observation: kappa coefficients ranged from 0.63 for footwear to
      0.77 for head wear. Agreement was variable for clothing worn while on the beach,
      with slight to fair agreement for sunglasses (kappa, 0.11) and footwear (kappa,
      0.23) and substantial agreement for upper body clothing (kappa, 0.79). Agreement
      between self-reported and observed sunburn was consistently lower (kappa, 0.21,
      0.33, and 0.39 for the face, legs, and arms, respectively), with participants
      reporting more sunburn on arrival than was observed. CONCLUSIONS: Overall, self
      report measures of time outside, sunscreen use, and clothing worn demonstrated
      good criterion validity when compared with observation and sunscreen swabbing.
      Sunscreen swabbing proved an effective procedure for detecting sunscreen at a
      beach setting.

PMID- 17043186
TI  - African tick bite fever: a not-so-uncommon illness in international travelers.
AB  - BACKGROUND: African tick bite fever is a rickettsial illness that has recently
      emerged as a significant disease among international travelers. The vector is the
      Amblyomma tick, which is endemic to sub-Saharan Africa and parts of the eastern
      Caribbean. OBSERVATIONS: We describe a middle-aged woman who returned from a
      mission trip to Zimbabwe with an influenzalike illness and inoculation eschar;
      she also had a history of travel to a game farm. Biopsy revealed a
      histopathologic pattern consistent with an infectious pathogenesis.
      Immunohistochemical staining confirmed the presence of rickettsial organisms. In
      light of the patient's history, the clinical constellation of signs and symptoms,
      and the results of ancillary laboratory testing, a diagnosis of African tick bite
      fever was made. The patient was treated with doxycycline hydrochloride and had an
      uncomplicated course. CONCLUSIONS: This report further highlights the
      epidemiological and clinical features of African tick bite fever. With the
      increase in international travel, it is important to recognize the illness in
      those who have been to endemic countries and to counsel patients regarding
      preventive measures for planned travel.

PMID- 17043187
TI  - Dermoscopy patterns of fibroepithelioma of pinkus.
AB  - BACKGROUND: Fibroepithelioma of Pinkus (FeP) is a rare variant of basal cell
      carcinoma that may clinically mimic a number of benign skin tumors. While the
      dermoscopic features of basal cell carcinoma have been studied extensively,
      little is known about the dermoscopic features of FeP. OBSERVATIONS:
      Retrospective evaluation of clinical records and digital clinical dermoscopic
      images of 10 histopathologically proved FePs (6 nonpigmented and 4 pigmented) was
      performed. Clinically, no FeP was correctly identified and, in half of all
      patients, a clinical differential diagnosis of purely benign skin lesions was
      made. Dermoscopy enabled the correct diagnosis in 9 of 10 FePs, based on the
      presence of fine arborizing vessels, either alone or associated with dotted
      vessels, and white streaks (in 100%, 70%, and 90% of lesions, respectively). In
      the 4 pigmented FePs, a structureless gray-brown area of pigmentation and
      variable numbers of gray-blue dots were observed, in addition. CONCLUSIONS:
      Dermoscopy is helpful in diagnosing FeP and in differentiating this variant of
      basal cell carcinoma from other benign skin tumors commonly included in the
      clinical differential diagnosis. This presumes, however, that dermoscopy is used
      as a first-line examination for all skin lesions, not only for those that are
      clinically suspect.

PMID- 17043188
TI  - Antimicrobial allergy from polyvinyl chloride gloves.
AB  - BACKGROUND: Contact allergy to plastic gloves is rare. Benzisothiazolinone is a
      biocide that is mainly used in industrial settings. We first suspected delayed
      type contact allergy to benzisothiazolinone from polyvinyl chloride (PVC) gloves
      in 2004. We looked through our medical records from 1991 to 2005 to find similar
      cases. OBSERVATIONS: We found a total of 8 patients who are allergic to
      benzisothiazolinone and who had had exacerbations of their hand dermatitis while
      using PVC gloves. Patch testing revealed that 3 of them had weak allergic or
      doubtful reactions to the glove materials. Six of them had used Evercare Soft,
      Medi-Point, or Derma Grip PVC gloves, which in chemical analysis were shown to
      contain 9 to 32 ppm of benzisothiazolinone. Seven of the patients worked in
      dentistry or health care and 1 in farming. All of them had had hand dermatitis
      for many years. CONCLUSIONS: To our knowledge, there have been no previous
      reports of contact allergy to antimicrobial agents in plastic gloves.
      Benzisothiazolinone is widely used as a biocide in the manufacture of disposable
      PVC gloves. Small amounts of benzisothiazolinone in the gloves may sensitize
      those who already have hand dermatitis. We recommend that all patients with hand
      dermatitis while using PVC gloves should be patch tested with
      benzisothiazolinone.

PMID- 17043189
TI  - Effect of topical vitamin D analogue on in vivo contact sensitization.
AB  - BACKGROUND: The immunomodulatory role of vitamin D and its analogues has been
      demonstrated in vitro and in vivo using animal models. We evaluated the effect of
      a vitamin D analogue, calcipotriene, in vivo on human subjects using a contact
      hypersensitivity model. OBSERVATIONS: Subjects were pretreated with topical
      calcipotriene, simulated solar radiation, or both on buttock skin. They were then
      sensitized and challenged using the contact allergen dinitrochlorobenzene. Immune
      response was measured by change in skinfold thickness before vs after elicitation
      across the challenge sites. CONCLUSIONS: Calcipotriene-treated individuals
      demonstrated 64% immunosuppression compared with untreated controls. This is
      equivalent to the immunosuppression induced by UV exposure.

PMID- 17043190
TI  - Successful treatment of recalcitrant chronic idiopathic urticaria with
      sulfasalazine.
AB  - BACKGROUND: Antihistamines are the standard treatment for chronic idiopathic
      urticaria (CIU). For patients whose urticaria is unresponsive to antihistamines,
      the treatment options are limited. During the previous decade, there have been
      several case reports demonstrating success with sulfasalazine therapy. In this
      article, we present a case series evaluating sulfasalazine therapy for
      antihistamine-unresponsive CIU. OBSERVATIONS: Nineteen patients with
      antihistamine-unresponsive CIU were treated with sulfasalazine between 2002 and
      2005. During sulfasalazine therapy, 14 patients (74%) reported significant
      improvement, 4 patients (21%) reported minimal improvement but were not satisfied
      with their symptom relief, and 1 patient (5%) reported a worsening of symptoms.
      Of the 13 patients who required systemic steroids to control their urticaria, all
      were able to reduce or discontinue steroid use during sulfasalazine therapy.
      Although 7 patients (37%) had adverse effects (eg, nausea, headache, mild or
      transient leukopenia, and transaminitis) that were thought to be caused by the
      use of sulfasalazine, they all kept taking the drug. CONCLUSIONS: This case
      series demonstrates that sulfasalazine can be a successful and safe treatment
      option for patients with CIU who have not responded adequately to treatment with
      antihistamines. Sulfasalazine was steroid sparing in all subjects who were
      steroid dependent.

PMID- 17043191
TI  - The pedal fungus reservoir.

PMID- 17043192
TI  - Methods in skin cancer prevention: using a question-driven approach to guide the
      choice of assessment approaches.

PMID- 17043193
TI  - Purpuric nodule on the shoulder. Targetoid hemosiderotic hemangioma.

PMID- 17043194
TI  - Bilateral lower eyelid masses. Orbital (intraorbital and extraocular) metastases
      in breast cancer.

PMID- 17043195
TI  - Painful plaque on a young man. Eccrine angiomatous hamartoma (EAH).

PMID- 17043196
TI  - Multiple annular plaques in an infant. Neonatal lupus erythematosus (NLE).

PMID- 17043197
TI  - Being a visual person: a dermatology residency interview perspective.

PMID- 17043198
TI  - Electrical shavers as a possible risk factor for metal exposure.

PMID- 17043199
TI  - Low but detectable serum levels of tacrolimus seen with the use of very dilute,
      extemporaneously compounded formulations of tacrolimus ointment in the treatment
      of patients with netherton syndrome.

PMID- 17043200
TI  - To perform a biopsy or excise suspected actinic keratoses: another view.

PMID- 17043201
TI  - Pimozide at least as safe and perhaps more effective than olanzapine for
      treatment of Morgellons disease.

PMID- 17043202
TI  - Adverse effects of cosmetic tattooing: an illustrative case of granulomatous
      dermatitis following the application of permanent makeup.

PMID- 17043203
TI  - Fever, episcleritis, epistaxis, and rash after safari holiday in Swaziland.

PMID- 17043204
TI  - Metastatic hidradenocarcinoma: efficacy of capecitabine.

PMID- 17043205
TI  - Leishmania major cutaneous leishmaniasis in HIV-positive patients does not spread
      to extralesional sites.

PMID- 17043206
TI  - Localized cutaneous sporotrichosis in a child.

PMID- 17043207
TI  - A case of CD56+ mycosis fungoides.

PMID- 17043208
TI  - Peristomal metastatic adenocarcinoma of the rectum.

PMID- 17043209
TI  - Cyclosporine resolves generalized pustular psoriasis of pregnancy.

PMID- 17043210
TI  - The significance of targetoid nevus.

PMID- 17043211
TI  - Predicting complex biology with simple chemistry.

PMID- 17043212
TI  - Smoking and lung cancer--a new role for an old toxicant?

PMID- 17043213
TI  - Profile of Jacob N. Israelachvili.

PMID- 17043214
TI  - Protective immunity to lethal challenge of the 1918 pandemic influenza virus by
      vaccination.
AB  - The remarkable infectivity and virulence of the 1918 influenza virus resulted in
      an unprecedented pandemic, raising the question of whether it is possible to
      develop protective immunity to this virus and whether immune evasion may have
      contributed to its spread. Here, we report that the highly lethal 1918 virus is
      susceptible to immune protection by a preventive vaccine, and we define its
      mechanism of action. Immunization with plasmid expression vectors encoding
      hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as
      neutralizing antibodies. Antibody specificity and titer were defined by a
      microneutralization and a pseudotype assay that could assess antibody specificity
      without the need for high-level biocontainment. This pseudotype inhibition assay
      can define evolving serotypes of influenza viruses and facilitate the development
      of immune sera and neutralizing monoclonal antibodies that may help contain
      pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid DNAs showed
      complete protection to lethal challenge. T cell depletion had no effect on
      immunity, but passive transfer of purified IgG from anti-H1(1918) immunized mice
      provided protective immunity for naive mice challenged with infectious 1918
      virus. Thus, humoral immunity directed at the viral HA can protect against the
      1918 pandemic virus.

PMID- 17043215
TI  - Recruitment of CD63 to Cryptococcus neoformans phagosomes requires acidification.
AB  - The subcellular localization of the cluster of differentiation 63 (CD63)
      tetraspanin and its interaction with the class II MHC antigen presentation
      pathway were examined in the context of phagocytosis by live cell imaging, by
      using monomeric red fluorescent protein-tagged mouse CD63 expressed in primary
      bone marrow-derived cell cultures. Upon phagocytosis of Cryptococcus neoformans
      and polystyrene beads, CD63 was recruited selectively to C. neoformans-containing
      phagosomes in a MyD88-independent acidification-dependent manner. Bead-containing
      phagosomes, within a C. neoformans-containing cell, acidified to a lesser extent
      and failed to recruit CD63 to a level detectable by microscopy. CD63 recruitment
      to yeast phagosomes occurred independently of class II MHC and LAMP-1. These
      observations indicate that the composition of distinct phagosomal compartments
      within the same cell is determined by phagosomal cargo and may affect the outcome
      of antigen processing and presentation.

PMID- 17043216
TI  - Effect of force on mononucleosomal dynamics.
AB  - Using single-molecule optical-trapping techniques, we examined the force-induced
      dynamic behavior of a single nucleosome core particle. Our experiments using the
      DNA construct containing the 601 nucleosome-positioning sequence revealed that
      the nucleosome unravels in at least two major stages. The first stage, which we
      attributed to the unraveling of the first DNA wrap around the histone octamer,
      could be mechanically induced in a reversible manner, and when kept at constant
      force within a critical force range, exhibited two-state hopping behavior. From
      the hopping data, we determined the force-dependent equilibrium constant and
      rates for opening/closing of the outer wrap. Our investigation of the second
      unraveling event at various loading rates, which we attributed to the inner DNA
      wrap, revealed that this unraveling event cannot be described as a simple two
      state process. We also looked at the behavior of the mononucleosome in a high
      salt buffer, which revealed that the outer DNA wrap is more sensitive to changes
      in the ionic environment than the inner DNA wrap. These findings are needed to
      understand the energetics of nucleosome remodeling.

PMID- 17043217
TI  - erbB2 is required for G protein-coupled receptor signaling in the heart.
AB  - erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian
      development and human disease. The absence of erbB2 signaling in cardiac myocytes
      results in dilated cardiomyopathy in mice, resembling the cardiotoxic effects
      observed in a subset of breast cancer patients treated with the anti-Her2
      antibody herceptin. Emerging evidence suggests that erbB2 is pivotal for
      integrating signaling networks involving multiple classes of extracellular
      signals. However, its role in G protein-coupled receptor (GPCR) signaling remains
      undefined. Because the activation of the MAPK pathway through GPCR signaling is
      important for cardiac homeostasis, we investigated whether erbB2 is required for
      GPCR-mediated MAPK signaling in wild-type and heart-specific erbB2 mutant mice.
      Here we demonstrate that erbB2, but not EGF receptor, is essential for MAPK
      activation induced by multiple GPCR agonists in cardiac myocytes. erbB2 is
      immunocomplexed with a GPCR in vivo and is transactivated after ligand treatment
      in vitro. Coexpression of erbB2 with GPCRs in heterologous cells results in
      ligand-dependent complex formation and MAPK activation. Furthermore, MAPK
      activation and cardiac contractility are markedly impaired in heart-specific
      erbB2 mutants infused with a GPCR agonist. These results reveal an essential
      mechanism requiring erbB2 as a coreceptor for GPCR signaling in the heart. The
      obligatory role of erbB2 in GPCR-dependent signaling may also be important in
      other cellular systems.

PMID- 17043218
TI  - The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with
      RNA polymerase II.
AB  - CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a
      repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II)
      interactions with Mediator. Here, we report that the ability of the Cdk8 module
      to prevent pol II interactions is independent of the Cdk8-dependent kinase
      activity. We use electron microscopy and single-particle reconstruction to
      demonstrate that the Cdk8 module forms a distinct structural entity that binds to
      the head and middle region of Mediator, thereby sterically blocking interactions
      with pol II.

PMID- 17043219
TI  - An intramolecular folding sensor for imaging estrogen receptor-ligand
      interactions.
AB  - Strategies for high-throughput analysis of interactions between various hormones
      and drugs with the estrogen receptor (ER) are crucial for accelerating the
      understanding of ER biology and pharmacology. Through careful analyses of the
      crystal structures of the human ER (hER) ligand-binding domain (hER-LBD) in
      complex with different ligands, we hypothesized that the hER-LBD intramolecular
      folding pattern could be used to distinguish ER agonists from selective ER
      modulators and pure antiestrogens. We therefore constructed and validated
      intramolecular folding sensors encoding various hER-LBD fusion proteins that
      could lead to split Renilla/firefly luciferase reporter complementation in the
      presence of the appropriate ligands. A mutant hER-LBD with low affinity for
      circulating estradiol was also identified for imaging in living subjects. Cells
      stably expressing the intramolecular folding sensors expressing wild-type and
      mutant hER-LBD were used for imaging ligand-induced intramolecular folding in
      living mice. This is the first hER-LBD intramolecular folding sensor suited for
      high-throughput quantitative analysis of interactions between hER with hormones
      and drugs using cell lysates, intact cells, and molecular imaging of small living
      subjects. The strategies developed can also be extended to study and image other
      important protein intramolecular folding systems.

PMID- 17043220
TI  - UV irradiation induces a postreplication DNA damage checkpoint.
AB  - Eukaryotic cells irradiated with high doses of UV exhibit cell-cycle responses
      referred to as G(1)/S, intraS, and G(2)/M checkpoints. After a moderate UV dose
      that approximates sunlight exposure and is lethal to fission yeast checkpoint
      mutants, we found unexpectedly that these cell-cycle responses do not occur.
      Instead, cells at all stages of the cell cycle carry lesions into S phase and
      delay cell-cycle progression for hours after the completion of bulk DNA
      synthesis. Both DNA replication and the checkpoint kinase, Chk1, are required to
      generate this cell-cycle response. UV-irradiation of Deltachk1 cells causes
      chromosome damage and loss of viability only after cells have replicated
      irradiated DNA and entered mitosis. These data suggest that an important
      physiological role of the cell-cycle response to UV is to provide time for
      postreplication repair.

PMID- 17043221
TI  - Unusual mechanical stability of a minimal RNA kissing complex.
AB  - By using optical tweezers, we have investigated the mechanical unfolding of a
      minimal kissing complex with only two G.C base pairs. The loop-loop interaction
      is exceptionally stable; it is disrupted at forces ranging from 7 to 30 pN, as
      compared with 14-20 pN for unfolding hairpins of 7 and 11 bp. By monitoring
      unfolding/folding trajectories of single molecules, we resolved the
      intermediates, measured their rate constants, and pinpointed the rate-limiting
      steps. The two hairpins unfold only after breaking the intramolecular kissing
      interaction, and the kissing interaction forms only after the folding of the
      hairpins. At forces that favor the unfolding of the hairpins, the entire RNA
      structure is kinetically stabilized by the kissing interaction, and extra work is
      required to unfold the metastable hairpins. The strong mechanical stability of
      even a minimal kissing complex indicates the importance of such loop-loop
      interactions in initiating and stabilizing RNA dimers in retroviruses.

PMID- 17043222
TI  - A rapid genome-scale response of the transcriptional oscillator to perturbation
      reveals a period-doubling path to phenotypic change.
AB  - Perturbation of the gated-synchrony system in yeast with phenelzine, an
      antidepressant drug used in the treatment of affective disorders in humans, leads
      to a rapid lengthening in the period of the genome-wide transcriptional
      oscillation. The effect is a concerted, genome-scale change in expression that is
      first seen in genes maximally expressed in the late-reductive phase of the cycle,
      doubling the length of the reductive phase within two cycles after treatment.
      Clustering of genes based on their temporal patterns of expression yielded just
      three super clusters whose trajectories through time could then be mapped into a
      simple 3D figure. In contrast to transcripts in the late-reductive phase, most
      transcripts do not show transients in expression relative to others in their
      temporal cluster but change their period in a concerted fashion. Mapping the
      trajectories of the transcripts into low-dimensional surfaces that can be
      represented by simple systems of differential equations provides a readily
      testable model of the dynamic architecture of phenotype. In this system, period
      doubling may be a preferred pathway for phenotypic change. As a practical matter,
      low-amplitude, genome-wide oscillations, a ubiquitous but often unrecognized
      attribute of phenotype, could be a source of seemingly intractable biological
      noise in microarray studies.

PMID- 17043223
TI  - Natural variation in Drosophila melanogaster diapause due to the insulin
      regulated PI3-kinase.
AB  - This study links natural variation in a Drosophila melanogaster overwintering
      strategy, diapause, to the insulin-regulated phosphatidylinositol 3-kinase (PI3
      kinase) gene, Dp110. Variation in diapause, a reproductive arrest, was associated
      with Dp110 by using Dp110 deletions and genomic rescue fragments in transgenic
      flies. Deletions of Dp110 increased the proportion of individuals in diapause,
      whereas expression of Dp110 in the nervous system, but not including the visual
      system, decreased it. The roles of phosphatidylinositol 3-kinase for both
      diapause in D. melanogaster and dauer formation in Caenorhabditis elegans suggest
      a conserved role for this kinase in both reproductive and developmental arrests
      in response to environmental stresses.

PMID- 17043224
TI  - Differential sensitivities of transcription factor target genes underlie cell
      type-specific gene expression profiles.
AB  - Changes in transcription factor levels and activities dictate developmental fate.
      Such a change might affect the full ensemble of target genes for a factor or only
      uniquely sensitive targets. We investigated the relationship among activity of
      the hematopoietic transcription factor GATA-1, chromatin occupancy, and target
      gene sensitivity. Graded activation of GATA-1 in GATA-1-null cells revealed high
      , intermediate-, and low-sensitivity targets. GATA-1 activity requirements for
      occupancy and transcription often correlated. A GATA-1 amino-terminal deletion
      mutant severely deregulated the low-sensitivity gene Tac-2. Thus, cells
      expressing different levels of a cell type-specific activator can have
      qualitatively distinct target gene expression patterns, and factor mutations
      preferentially deregulate low-sensitivity genes. Unlike other target genes, GATA
      1-mediated Tac-2 regulation was bimodal, with activation followed by repression,
      and the coregulator Friend of GATA-1 (FOG-1) selectively mediated repression. A
      GATA-1 mutant defective in FOG-1 binding occupied a Tac-2 regulatory region at
      levels higher than wild-type GATA-1, whereas FOG-1 facilitated chromatin
      occupancy at a distinct target site. These results indicate that FOG-1 is a
      determinant of GATA factor target gene sensitivity by either facilitating or
      opposing chromatin occupancy.

PMID- 17043225
TI  - An algorithm for assembly of ordered restriction maps from single DNA molecules.
AB  - The restriction mapping of a massive number of individual DNA molecules by
      optical mapping enables assembly of physical maps spanning mammalian and plant
      genomes; however, not through computational means permitting completely de novo
      assembly. Existing algorithms are not practical for genomes larger than lower
      eukaryotes due to their high time and space complexity. In many ways, sequence
      assembly parallels map assembly, so that the overlap-layout-consensus strategy,
      recently shown effective in assembling very large genomes in feasible time, sheds
      new light on solving map construction issues associated with single molecule
      substrates. Accordingly, we report an adaptation of this approach as the formal
      basis for de novo optical map assembly and demonstrate its computational
      feasibility for assembly of very large genomes. As such, we discuss assembly
      results for a series of genomes: human, plant, lower eukaryote and bacterial.
      Unlike sequence assembly, the optical map assembly problem is actually more
      complex because restriction maps from single molecules are constructed,
      manifesting errors stemming from: missing cuts, false cuts, and high variance of
      estimated fragment sizes; chimeric maps resulting from artifactually merged
      molecules; and true overlap scores that are "in the noise" or "slightly above the
      noise." We address these problems, fundamental to many single molecule
      measurements, by an effective error correction method using global overlap
      information to eliminate spurious overlaps and chimeric maps that are otherwise
      difficult to identify.

PMID- 17043226
TI  - Powering the planet: chemical challenges in solar energy utilization.
AB  - Global energy consumption is projected to increase, even in the face of
      substantial declines in energy intensity, at least 2-fold by midcentury relative
      to the present because of population and economic growth. This demand could be
      met, in principle, from fossil energy resources, particularly coal. However, the
      cumulative nature of CO(2) emissions in the atmosphere demands that holding
      atmospheric CO(2) levels to even twice their preanthropogenic values by
      midcentury will require invention, development, and deployment of schemes for
      carbon-neutral energy production on a scale commensurate with, or larger than,
      the entire present-day energy supply from all sources combined. Among renewable
      energy resources, solar energy is by far the largest exploitable resource,
      providing more energy in 1 hour to the earth than all of the energy consumed by
      humans in an entire year. In view of the intermittency of insolation, if solar
      energy is to be a major primary energy source, it must be stored and dispatched
      on demand to the end user. An especially attractive approach is to store solar
      converted energy in the form of chemical bonds, i.e., in a photosynthetic process
      at a year-round average efficiency significantly higher than current plants or
      algae, to reduce land-area requirements. Scientific challenges involved with this
      process include schemes to capture and convert solar energy and then store the
      energy in the form of chemical bonds, producing oxygen from water and a reduced
      fuel such as hydrogen, methane, methanol, or other hydrocarbon species.

PMID- 17043227
TI  - Time scales of membrane fusion revealed by direct imaging of vesicle fusion with
      high temporal resolution.
AB  - Membrane fusion is a vital process of life involved, for example, in cellular
      secretion via exocytosis, signaling between nerve cells, and virus infection. In
      both the life sciences and bioengineering, controlled membrane fusion has many
      possible applications, such as drug delivery, gene transfer, chemical
      microreactors, or synthesis of nanomaterials. Until now, the fusion dynamics has
      been elusive because direct observations have been limited to time scales that
      exceed several milliseconds. Here, the fusion of giant lipid vesicles is induced
      in a controlled manner and monitored with a temporal resolution of 50 micros. Two
      different fusion protocols are used that are based on synthetic fusogenic
      molecules and electroporation. For both protocols, the opening of the fusion
      necks is very fast, with an average expansion velocity of centimeters per second.
      This velocity indicates that the initial formation of a single fusion neck can be
      completed in a few hundred nanoseconds.

PMID- 17043228
TI  - Renal cortical cyclooxygenase 2 expression is differentially regulated by
      angiotensin II AT(1) and AT(2) receptors.
AB  - Macula densa cyclooxygenase 2 (COX-2)-derived prostaglandins serve as important
      modulators of the renin-angiotensin system, and cross-talk exists between these
      two systems. Cortical COX-2 induction by angiotensin-converting enzyme (ACE)
      inhibitors or AT(1) receptor blockers (ARBs) suggests that angiotensin II may
      inhibit cortical COX-2 by stimulating the AT(1) receptor pathway. In the present
      studies we determined that chronic infusion of either hypertensive or
      nonhypertensive concentrations of angiotensin II attenuated cortical COX-2.
      Angiotensin II infusion reversed cortical COX-2 elevation induced by ACE
      inhibitors. However, we found that angiotensin II infusion further stimulated
      cortical COX-2 elevation induced by ARBs, suggesting a potential role for an
      AT(2) receptor-mediated pathway when the AT(1) receptor was inhibited. Both WT
      and AT(2) receptor knockout mice were treated for 7 days with either ACE
      inhibitors or ARBs. Cortical COX-2 increased to similar levels in response to ACE
      inhibition in both knockout and WT mice. In WT mice ARBs increased cortical COX-2
      more than ACE inhibitors, and this stimulation was attenuated by the AT(2)
      receptor antagonist PD123319. In the knockout mice ARBs led to significantly less
      cortical COX-2 elevation, which was not attenuated by PD123319. PCR confirmed
      AT(1a) and AT(2) receptor expression in the cultured macula densa cell line
      MMDD1. Angiotensin II inhibited MMDD1 COX-2, and CGP42112A, an AT(2) receptor
      agonist, stimulated MMDD1 COX-2. In summary, these results demonstrate that
      macula densa COX-2 expression is oppositely regulated by AT(1) and AT(2)
      receptors and suggest that AT(2) receptor-mediated cortical COX-2 elevation may
      mediate physiologic effects that modulate AT(1)-mediated responses.

PMID- 17043229
TI  - PGC-1alpha controls hepatitis B virus through nutritional signals.
AB  - Hepatitis B virus (HBV) is a 3.2-kb DNA virus that replicates preferentially in
      the liver. Liver-enriched nuclear receptors (NRs) play a major role in the HBV
      life cycle, operating as essential transcription factors for viral gene
      expression. Notably, these NRs are also key players in metabolic processes that
      occur in the liver, serving as central transcription factors for key enzymes of
      gluconeogenesis, fatty acid beta-oxidation, and ketogenesis. However, the
      association between these metabolic events and HBV gene expression is poorly
      understood. Here we show that peroxisome proliferator-activated receptor-gamma
      coactivator 1alpha (PGC-1alpha), a major metabolic regulator and a coactivator of
      key gluconeogenic genes, robustly coactivates HBV transcription. We further
      demonstrate that the liver-enriched NR hepatocyte nuclear factor 4alpha that
      binds HBV plays an important role in this process. Physiologically, we show that
      a short-term fast that turns on the gluconeogenic program robustly induces HBV
      gene expression in vivo. This induction is completely reversible by refeeding and
      depends on PGC-1alpha. We conclude that HBV is tightly regulated by changes in
      the body's nutritional state through the metabolic regulator PGC-1alpha. Our data
      provide evidence for nutrition signaling to control viral gene expression and
      life cycle and thus ascribe to metabolism an important role in virus-host
      interaction.

PMID- 17043230
TI  - Emergence of a bacterial clone with enhanced virulence by acquisition of a phage
      encoding a secreted phospholipase A2.
AB  - The molecular basis of pathogen clone emergence is relatively poorly understood.
      Acquisition of a bacteriophage encoding a previously unknown secreted
      phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence
      in the mid-1980s of a new hypervirulent clone of serotype M3 group A
      Streptococcus. Although several lines of circumstantial evidence suggest that
      SlaA is a virulence factor, this issue has not been addressed experimentally. We
      found that an isogenic DeltaslaA mutant strain was significantly impaired in
      ability to adhere to and kill human epithelial cells compared with the wild-type
      parental strain. The mutant strain was less virulent for mice than the wild-type
      strain, and immunization with purified SlaA significantly protected mice from
      invasive disease. Importantly, the mutant strain was significantly attenuated for
      colonization in a monkey model of pharyngitis. We conclude that transductional
      acquisition of the ability of a GAS strain to produce SlaA enhanced the spread
      and virulence of the serotype M3 precursor strain. Hence, these studies
      identified a crucial molecular event underlying the evolution, rapid emergence,
      and widespread dissemination of unusually severe human infections caused by a
      distinct bacterial clone.

PMID- 17043231
TI  - The genomic landscape of histone modifications in human T cells.
AB  - To understand the molecular basis that supports the dynamic gene expression
      programs unique to T cells, we investigated the genomic landscape of activating
      histone modifications, including histone H3 K9/K14 diacetylation (H3K9acK14ac),
      H3 K4 trimethylation (H3K4me3), and the repressive histone modification H3 K27
      trimethylation (H3K27me3) in primary human T cells. We show that H3K9acK14ac and
      H3K4me3 are associated with active genes required for T cell function and
      development, whereas H3K27me3 is associated with silent genes that are involved
      in development in other cell types. Unexpectedly, we find that 3,330 gene
      promoters are associated with all of these histone modifications. The gene
      expression levels are correlated with both the absolute and relative levels of
      the activating H3K4me3 and the repressive H3K27me3 modifications. Our data reveal
      that rapidly inducible genes are associated with the H3 acetylation and H3K4me3
      modifications, suggesting they assume a chromatin structure poised for
      activation. In addition, we identified a subpopulation of chromatin regions that
      are associated with high levels of H3K4me3 and H3K27me3 but low levels of
      H3K9acK14ac. Therefore, these regions have a distinctive chromatin modification
      pattern and thus may represent a distinct class of chromatin domains.

PMID- 17043232
TI  - Hereditary family signature of facial expression.
AB  - Although facial expressions of emotion are universal, individual differences
      create a facial expression "signature" for each person; but, is there a unique
      family facial expression signature? Only a few family studies on the heredity of
      facial expressions have been performed, none of which compared the gestalt of
      movements in various emotional states; they compared only a few movements in one
      or two emotional states. No studies, to our knowledge, have compared movements of
      congenitally blind subjects with their relatives to our knowledge. Using two
      types of analyses, we show a correlation between movements of congenitally blind
      subjects with those of their relatives in think-concentrate, sadness, anger,
      disgust, joy, and surprise and provide evidence for a unique family facial
      expression signature. In the analysis "in-out family test," a particular movement
      was compared each time across subjects. Results show that the frequency of
      occurrence of a movement of a congenitally blind subject in his family is
      significantly higher than that outside of his family in think-concentrate,
      sadness, and anger. In the analysis "the classification test," in which
      congenitally blind subjects were classified to their families according to the
      gestalt of movements, results show 80% correct classification over the entire
      interview and 75% in anger. Analysis of the movements' frequencies in anger
      revealed a correlation between the movements' frequencies of congenitally blind
      individuals and those of their relatives. This study anticipates discovering
      genes that influence facial expressions, understanding their evolutionary
      significance, and elucidating repair mechanisms for syndromes lacking facial
      expression, such as autism.

PMID- 17043234
TI  - Late Archean rise of aerobic microbial ecosystems.
AB  - We report the (13)C content of preserved organic carbon for a 150 million-year
      section of late Archean shallow and deepwater sediments of the Hamersley Province
      in Western Australia. We find a (13)C enrichment of approximately 10 per thousand
      in organic carbon of post-2.7-billion-year-old shallow-water carbonate rocks
      relative to deepwater sediments. The shallow-water organic-carbon (13)C content
      has a 29 per thousand range in values (-57 to -28 per thousand), and it contrasts
      with the less variable but strongly (13)C-depleted (-40 to -45 per thousand)
      organic carbon in deepwater sediments. The (13)C enrichment likely represents
      microbial habitats not as strongly influenced by assimilation of methane or other
      (13)C-depleted substrates. We propose that continued oxidation of shallow
      settings favored the expansion of aerobic ecosystems and respiring organisms,
      and, as a result, isotopic signatures of preserved organic carbon in shallow
      settings approached that of photosynthetic biomass. Facies analysis of published
      carbon-isotopic records indicates that the Hamersley shallow-water signal may be
      representative of a late Archean global signature and that it preceded a similar,
      but delayed, (13)C enrichment of deepwater deposits. The data suggest that a
      global-scale expansion of oxygenated habitats accompanied the progression away
      from anaerobic ecosystems toward respiring microbial communities fueled by
      oxygenic photosynthesis before the oxygenation of the atmosphere after 2.45
      billion years ago.

PMID- 17043233
TI  - Vitamin K-dependent proteins in Ciona intestinalis, a basal chordate lacking a
      blood coagulation cascade.
AB  - We have isolated and sequenced several cDNAs derived from the sea squirt Ciona
      intestinalis that encode vitamin K-dependent proteins. Four of these encode gamma
      carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci
      Gla1 through Ci-Gla4. Two additional cDNAs encode the apparent orthologs of gamma
      glutamyl carboxylase and vitamin K epoxide reductase. Ci-Gla1 undergoes gamma
      glutamyl carboxylation when expressed in CHO cells and is homologous to Gla-RTK,
      a putative receptor tyrosine kinase previously identified in a related ascidian.
      The remaining three Gla domain proteins are similar to proteins that participate
      in fundamental developmental processes, complement regulation, and blood
      coagulation. These proteins are generally expressed at low levels throughout
      development and exhibit either relatively constant expression (Ci-Gla1, gamma
      glutamyl carboxylase, and vitamin K epoxide reductase) or spatiotemporal
      regulation (Ci-Gla2, -3, and -4). These results demonstrate the evolutionary
      emergence of the vitamin K-dependent Gla domain before the divergence of
      vertebrates and urochordates and suggest novel functions for Gla domain proteins
      distinct from their roles in vertebrate hemostasis. In addition, these findings
      highlight the usefulness of C. intestinalis as a model organism for investigating
      vitamin K-dependent physiological phenomena, which may be conserved among the
      chordate subphyla.

PMID- 17043235
TI  - Global aggregation of newly translated proteins in an Escherichia coli strain
      deficient of the chaperonin GroEL.
AB  - In a newly isolated temperature-sensitive lethal Escherichia coli mutant
      affecting the chaperonin GroEL, we observed wholesale aggregation of newly
      translated proteins. After temperature shift, transcription, translation, and
      growth slowed over two to three generations, accompanied by filamentation and
      accretion (in approximately 2% of cells) of paracrystalline arrays containing
      mutant chaperonin complex. A biochemically isolated inclusion body fraction
      contained the collective of abundant proteins of the bacterial cytoplasm as
      determined by SDS/PAGE and proteolysis/MS analyses. Pulse-chase experiments
      revealed that newly made proteins, but not preexistent ones, were recruited to
      this insoluble fraction. Although aggregation of "stringent" GroEL/GroES
      dependent substrates may secondarily produce an "avalanche" of aggregation, the
      observations raise the possibility, supported by in vitro refolding experiments,
      that the widespread aggregation reflects that GroEL function supports the proper
      folding of a majority of newly translated polypeptides, not just the limited
      number indicated by interaction studies and in vitro experiments.

PMID- 17043236
TI  - Distance measurements reveal a common topology of prokaryotic voltage-gated ion
      channels in the lipid bilayer.
AB  - Voltage-dependent ion channels are fundamental to the physiology of excitable
      cells because they underlie the generation and propagation of the action
      potential and excitation-contraction coupling. To understand how ion channels
      work, it is important to determine their structures in different conformations in
      a membrane environment. The validity of the crystal structure for the prokaryotic
      K(+) channel, K(V)AP, has been questioned based on discrepancies with biophysical
      data from functional eukaryotic channels, underlining the need for independent
      structural data under native conditions. We investigated the structural
      organization of two prokaryotic voltage-gated channels, NaChBac and K(V)AP, in
      liposomes by using luminescence resonance energy transfer. We describe here a
      transmembrane packing representation of the voltage sensor and pore domains of
      the prokaryotic Na channel, NaChBac. We find that NaChBac and K(V)AP share a
      common arrangement in which the structures of the Na and K selective pores and
      voltage-sensor domains are conserved. The packing arrangement of the voltage
      sensing region as determined by luminescence resonance energy transfer differs
      significantly from that of the K(V)AP crystal structure, but resembles that of
      the eukaryotic K(V)1.2 crystal structure. However, the voltage-sensor domain in
      prokaryotic channels is closer to the pore domain than in the K(V)1.2 structure.
      Our results indicate that prokaryotic and eukaryotic channels that share similar
      functional properties have similar helix arrangements, with differences arising
      likely from the later introduction of additional structural elements.

PMID- 17043237
TI  - An inherent role of microtubule network in the action of nuclear receptor.
AB  - Estrogen receptor alpha (ERalpha) functions as both a transcription factor and a
      mediator of rapid estrogen signaling. Recent studies have shown a role for
      ERalpha-interacting membranous and cytosolic proteins in ERalpha action, but our
      understanding of the role of the microtubule network in the modulation of ERalpha
      signaling remains unclear. Here we found that endogenous ERalpha associates with
      microtubules through the microtubule-binding protein hematopoietic PBX
      interaction protein (HPIP). Biochemical and RNA-interference studies demonstrated
      that HPIP influences ERalpha-dependent rapid estrogen signaling by acting as a
      scaffold protein and recruits Src kinase and the p85 subunit of
      phosphatidylinositol 3-kinase to a complex with ERalpha, which in turn stimulates
      AKT and MAPK. We also found that ERalpha interacts with beta-tubulin through
      HPIP. Destabilization of microtubules activated ERalpha signaling, whereas
      stabilization of microtubules repressed ERalpha transcriptional activity in a
      HPIP-dependent manner. These findings revealed a role for HPIP-microtubule
      complex in regulating 17beta-estradiol-ERalpha responses in mammalian cells and
      discovered an inherent role of microtubules in the action of nuclear receptor.

PMID- 17043238
TI  - Wild-type microglia extend survival in PU.1 knockout mice with familial
      amyotrophic lateral sclerosis.
AB  - The most common inherited form of amyotrophic lateral sclerosis (ALS), a
      neurodegenerative disease affecting adult motoneurons, is caused by dominant
      mutations in the ubiquitously expressed Cu(2+)/Zn(2+) superoxide dismutase
      (SOD1). Recent studies suggest that glia may contribute to motoneuron injury in
      animal models of familial ALS. To determine whether the expression of mutant SOD1
      (mSOD1(G93A)) in CNS microglia contributes to motoneuron injury, PU.1(-/-) mice
      that are unable to develop myeloid and lymphoid cells received bone marrow
      transplants resulting in donor-derived microglia. Donor-derived microglia from
      mice overexpressing mSOD1(G93A), an animal model of familial ALS, transplanted
      into PU.1(-/-) mice could not induce weakness, motoneuron injury, or an ALS-like
      disease. To determine whether expression of mSOD1(G93A) in motoneurons and
      astroglia, as well as microglia, was required to produce motoneuron disease,
      PU.1(-/-) mice were bred with mSOD1(G93A) mice. In mSOD1(G93A)/PU.1(-/-) mice,
      wild-type donor-derived microglia slowed motoneuron loss and prolonged disease
      duration and survival when compared with mice receiving mSOD1(G93A) expressing
      cells or mSOD1(G93A) mice. In vitro studies confirmed that wild-type microglia
      were less neurotoxic than similarly cultured mSOD1(G93A) microglia. Compared with
      wild-type microglia, mSOD1(G93A) microglia produced and released more superoxide
      and nitrite+nitrate, and induced more neuronal death. These data demonstrate that
      the expression of mSOD1(G93A) results in activated and neurotoxic microglia, and
      suggests that the lack of mSOD1(G93A) expression in microglia may contribute to
      motoneuron protection. This study confirms the importance of microglia as a
      double-edged sword, and focuses on the importance of targeting microglia to
      minimize cytotoxicity and maximize neuroprotection in neurodegenerative diseases.

PMID- 17043239
TI  - Human DNA polymerase kappa forms nonproductive complexes with matched primer
      termini but not with mismatched primer termini.
AB  - Human DNA polymerase kappa (pol kappa) is a member of the Y family of DNA
      polymerases that function in translesion synthesis. It synthesizes DNA with
      moderate fidelity and does not efficiently incorporate nucleotides opposite DNA
      lesions. Pol kappa has the unusual ability to efficiently extend from mismatched
      primer termini, and it extends readily from nucleotides inserted by other DNA
      polymerases opposite a variety of DNA lesions. All of this has suggested that pol
      kappa functions during the extension step of translesion synthesis. Here, we have
      carried out pre-steady-state kinetic studies of pol kappa using DNA with matched
      and mismatched primer termini. Interestingly, we find that mismatches present
      only a modest kinetic barrier to nucleotide incorporation by pol kappa. Moreover,
      and quite surprisingly, active-site titrations revealed that the concentration of
      active pol kappa is very low with matched DNA, and from DNA trapping experiments
      we determined that this was due to the formation of nonproductive protein.DNA
      complexes. In marked contrast, we found that the concentration of active pol
      kappa was six-fold greater with mismatched DNA than with matched DNA. Thus, pol
      kappa forms nonproductive complexes with matched but not with mismatched DNA.
      From these observations, we conclude that pol kappa has evolved to specifically
      function on DNA substrates with aberrant primer-terminal base pairs, such as the
      ones it would encounter during the extension step of translesion synthesis.

PMID- 17043240
TI  - Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the
      complex network of hemostasis.
AB  - This article demonstrates that a simple chemical model system, built by using a
      modular approach, may be used to predict the spatiotemporal dynamics of
      initiation of blood clotting in the complex network of hemostasis. Microfluidics
      was used to create in vitro environments that expose both the complex network and
      the model system to surfaces patterned with patches presenting clotting stimuli.
      Both systems displayed a threshold response, with clotting initiating only on
      isolated patches larger than a threshold size. The magnitude of the threshold
      patch size for both systems was described by the Damkohler number, measuring
      competition of reaction and diffusion. Reaction produces activators at the patch,
      and diffusion removes activators from the patch. The chemical model made
      additional predictions that were validated experimentally with human blood
      plasma. These experiments show that blood can be exposed to significant amounts
      of clot-inducing stimuli, such as tissue factor, without initiating clotting.
      Overall, these results demonstrate that such chemical model systems, implemented
      with microfluidics, may be used to predict spatiotemporal dynamics of complex
      biochemical networks.

PMID- 17043241
TI  - Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin
      dependent kinase 1.
AB  - Androgen receptors (ARs) are phosphorylated at multiple sites in response to
      ligand binding, but the kinases mediating AR phosphorylation and the importance
      of these kinases in AR function have not been established. Here we show that
      cyclin-dependent kinase 1 (Cdk1) mediates AR phosphorylation at Ser-81 and
      increases AR protein expression, and that Cdk1 inhibitors decrease AR Ser-81
      phosphorylation, protein expression, and transcriptional activity in prostate
      cancer (PCa) cells. The decline in AR protein expression mediated by the Cdk
      inhibitor roscovitine was prevented by proteosome inhibitors, indicating that
      Cdk1 stabilizes AR protein, although roscovitine also decreased AR message
      levels. Analysis of an S81A AR mutant demonstrated that this site is not required
      for transcriptional activity or Cdk1-mediated AR stabilization in transfected
      cells. The AR is active and seems to be stabilized by low levels of androgen in
      "androgen-independent" PCas that relapse subsequent to androgen-deprivation
      therapy. Significantly, the expression of cyclin B and Cdk1 was increased in
      these tumors, and treatment with roscovitine abrogated responses to low levels of
      androgen in the androgen-independent C4-2 PCa cell line. Taken together, these
      findings identify Cdk1 as a Ser-81 kinase and indicate that Cdk1 stabilizes AR
      protein by phosphorylation at a site(s) distinct from Ser-81. Moreover, these
      results indicate that increased Cdk1 activity is a mechanism for increasing AR
      expression and stability in response to low androgen levels in androgen
      independent PCas, and that Cdk1 antagonists may enhance responses to androgen
      deprivation therapy.

PMID- 17043242
TI  - Microsporidian mitosomes retain elements of the general mitochondrial targeting
      system.
AB  - Microsporidia are intracellular parasites that infect a variety of animals,
      including humans. As highly specialized parasites, they are characterized by a
      number of unusual adaptations, many of which are manifested as extreme reduction
      at the molecular, biochemical, and cellular levels. One interesting aspect of
      reduction is the mitochondrion. Microsporidia were long considered to be
      amitochondriate, but recently a tiny mitochondrion-derived organelle called the
      mitosome was detected. The molecular function of this organelle remains poorly
      understood. The mitosome has no genome, so it must import all its proteins from
      the cytosol. In other fungi, the mitochondrial protein import machinery consists
      of a network series of heterooligomeric translocases and peptidases, but in
      microsporidia, only a few subunits of some of these complexes have been
      identified to date. Here, we look at targeting sequences of the microsporidian
      mitosomal import system and show that mitosomes do in some cases still use N
      terminal and internal targeting sequences that are recognizable by import systems
      of mitochondria in yeast. Furthermore, we have examined the function of the inner
      membrane peptidase processing enzyme and demonstrate that mitosomal substrates of
      this enzyme are processed to mature proteins in one species with a simplified
      processing complex, Antonospora locustae. However, in Encephalitozoon cuniculi,
      the processing complex is lost altogether, and the preprotein substrate functions
      with the targeting leader still attached. This report provides direct evidence
      for presequencing processing in mitosomes and also shows how a complex molecular
      system has continued to degenerate throughout the evolution of microsporidia.

PMID- 17043244
TI  - Isolation, characterization, and genetic complementation of a cellular mutant
      resistant to retroviral infection.
AB  - By using a genetic screen, we have isolated a mammalian cell line that is
      resistant to infection by retroviruses that are derived from the murine leukemia
      virus, human immunodeficiency virus type 1, and feline immunodeficiency virus. We
      demonstrate that the cell line is genetically recessive for the resistance, and
      hence it is lacking a factor enabling infection by retroviruses. The block to
      infection is early in the life cycle, at the poorly understood uncoating stage.
      We implicate the proteasome at uncoating by completely rescuing the resistant
      phenotype with the proteasomal inhibitor MG-132. We further report on the
      complementation cloning of a gene (MRI, modulator of retrovirus infection) that
      can also act to reverse the inhibition of infection in the mutant cell line.
      These data implicate a role for the proteasome during uncoating, and they suggest
      that MRI is a regulator of this activity. Finally, we reconcile our findings and
      other published data to suggest a model for the involvement of the proteasome in
      the early phase of the retroviral life cycle.

PMID- 17043243
TI  - Galectin-1 is essential in tumor angiogenesis and is a target for
      antiangiogenesis therapy.
AB  - We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor
      anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is
      overexpressed in endothelial cells of different human tumors. Expression
      knockdown in cultured endothelial cells inhibits cell proliferation and
      migration. The importance of gal-1 in angiogenesis is illustrated in the
      zebrafish model, where expression knockdown results in impaired vascular guidance
      and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is
      demonstrated in gal-1-null mice, in which tumor growth is markedly impaired
      because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1
      null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal
      1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.

PMID- 17043245
TI  - A role for adrenomedullin as a pain-related peptide in the rat.
AB  - Adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family
      and is a well known potent vasodilator. We show here that AM is a powerful pain
      inducing neuropeptide. AM-like immunoreactivity is widely distributed in both
      CGRP-containing and lectin IB4-binding nociceptors in dorsal root ganglion and
      axon terminals in the superficial dorsal horn of the rat spinal cord. Specific
      binding sites for the radioligand, [(125)I]AM13-52 as well as immunoreactivity
      for receptor markers such as the calcitonin receptor-like receptor and three
      receptor-activity-modifying proteins are localized in the superficial dorsal
      horn, demonstrating the existence of AM/CGRP receptors in this region.
      Intrathecal injection of rat AM1-50, dose- and time-dependently, induced long
      lasting heat hyperalgesia and increased the phosphorylation of Akt and GSK3beta
      in the dorsal horn. Pre- and posttreatments with the AM receptor antagonist AM22
      52 and PI3 kinase inhibitors (LY294002 and Wortmannin) significantly blocked or
      reversed AM-induced heat hyperalgesia. Pre- and posttreatments with AM22-52 and
      Wortmannin also significantly blocked or reversed intraplantar capsaicin-induced
      heat hyperalgesia. Taken together, our results demonstrate that AM acts as a pain
      inducing peptide in the dorsal horn. By activating specific receptors (likely
      AM2) and the PI3K/Akt/GSK3beta signaling pathway, AM could play a significant
      role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia.

PMID- 17043246
TI  - Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in
      leukocyte function.
AB  - Traditionally, PGD(2) has been considered to be a pro-inflammatory mediator,
      acting via classical PG receptors, such as the PGD(2) receptor (DP). PGD(2) is
      degraded rapidly in vitro and in vivo to a variety of metabolites, the majority
      of which were thought, until recently, to be physiologically inactive. Several
      "inactive" metabolites, particularly 15d-PGJ(2), have been shown to have wide
      ranging effects on leukocytes and other cell types, however, and a potentially
      important anti-inflammatory role for PGD(2) has now been recognized, and the
      complexity of PGD(2) signaling is beginning to be elucidated. PGD(2) and its
      metabolites are biologically active over a broad concentration range, and,
      intriquingly, it appears that there are marked concentration-dependent variations
      in the consequences of signaling by these eicosanoids, which have the potential
      to exert pro- and anti-inflammatory effects. For example, the actions of PGD(2)
      can influence multiple stages in the life of the mature eosinophil, from causing
      its release from the bone marrow to inducing its recruitment and activation and,
      ultimately, regulating its apoptosis. This review is concerned with the diverse
      responses induced in leukocytes by PGD(2) and its metabolites and the signaling
      mechanisms which are thought to be responsible for them.

PMID- 17043247
TI  - Incidence and survival rates for young blacks with nasopharyngeal carcinoma in
      the United States.
AB  - OBJECTIVES: To compare the incidence rates of nasopharyngeal carcinoma (NPC)
      among US black, white, and Asian/Pacific Islander (Asian) populations, with a
      focus on those diagnosed before age 20 years and between ages 20 and 29 years.
      Our secondary objective was to determine differences in survival rates between US
      blacks, whites, and Asians with NPC who were younger than 30 years. DESIGN: Data
      from the National Cancer Institute Surveillance, Epidemiology, and End Results
      (SEER) tumor registry system were used to determine incidence and survival rates
      for cases of NPC diagnosed in the specified age groups between 1973 and 2002.
      PATIENTS: Blacks, whites, and Asians younger than 30 years with NPC. MAIN OUTCOME
      MEASURES: Incidence rates and 2- and 5-year survival rates. RESULTS: From 1973 to
      2002, incidence rates per 1 million persons, adjusted to the 2000 standard
      population, for blacks, whites, and Asians younger than 20 years with NPC were
      1.61 (n=43), 0.61 (n=99), and 0.95 (n=18), respectively. The incidence rate ratio
      of blacks to Asians younger than 20 years was 1.69 (95% confidence interval [CI],
      0.96-3.12) (P=.07), while the rate ratio for blacks to whites was 2.66 (95% CI,
      1.82-3.85) (P<.001). From ages 20 to 29 years, rates increased slightly in blacks
      (1.87) and whites (0.96), while increasing dramatically in Asians (7.18). Two-
      and 5-year relative survival rates in blacks younger than 30 years were 84% and
      64%, respectively, with little variation between races in this age group.
      CONCLUSIONS: Blacks younger than 20 years have increased incidence rates of NPC
      relative to whites and may be the only group having a higher NPC incidence rate
      than Asians. Two- and 5-year survival rates of blacks, whites, and Asians younger
      than 30 years with NPC are similar.

PMID- 17043248
TI  - Association between development of hypothyroidism and improved survival in
      patients with head and neck cancer.
AB  - OBJECTIVE: To determine if the development of hypothyroidism has an effect on the
      outcome of advanced-stage head and neck squamous cell carcinoma. DESIGN:
      Retrospective database analysis. SETTING: Tertiary care center. PATIENTS: The
      study population comprised 155 patients with advanced-stage head and neck
      squamous cell carcinoma. INTERVENTIONS: Patients underwent radiation therapy
      alone or in combination with chemotherapy and surgery when indicated. MAIN
      OUTCOME MEASURES: Kaplan-Meier analysis was used to assess survival, not
      adjusting for timing of the detection of hypothyroidism. The following 2 analyses
      were then performed to adjust for the timing of detection: (1) hypothyroidism was
      assessed as a time-varying covariate in a Cox proportional hazards model and (2)
      a landmark analysis was conducted at 9, 12, 15, 18, 21, and 24 months using the
      Kaplan-Meier method. RESULTS: Of the 155 patients, 59 developed hypothyroidism,
      defined as a thyrotropin level greater than 5.5 mIU/L (institutional value). An
      unadjusted Kaplan-Meier analysis indicated that patients who develop
      hypothyroidism have significantly better survival than patients who do not
      (P<.001, log-rank test). After adjusting for the timing of hypothyroidism, a Cox
      proportional hazards analysis indicated that survival was better, but not
      statistically significant, for patients who developed hypothyroidism (hazard
      ratio, 0.62; P=.12); results from a landmark analysis supported this finding (P
      values ranged from .11 to .19). CONCLUSIONS: Development of hypothyroidism may be
      associated with improved survival and increased recurrence-free survival. Larger,
      prospective studies appear warranted to test the beneficial effect of
      hypothyroidism.

PMID- 17043249
TI  - Importance of routine evaluation of the thyroid gland prior to open partial
      laryngectomy.
AB  - OBJECTIVES: To determine the incidence and presentation of synchronous thyroid
      lesions in a patient population undergoing open partial laryngectomy (OPL), and
      to determine whether routine preoperative evaluation of the thyroid gland prior
      to OPL is useful to identify synchronous thyroid lesions in order to reduce the
      need for reoperation in this complex patient population. DESIGN: Retrospective
      medical chart review. SETTING: Academic institution. PATIENTS: Sixty-seven
      consecutive patients with laryngeal tumors who had undergone OPL from 1996 to
      2005. INTERVENTIONS: Charts of 67 consecutive patients with laryngeal tumors who
      underwent OPL in 1996 to 2005 have been reviewed for synchronous thyroid lesions.
      For all patients, reports of (1) complete preoperative examination findings, (2)
      inpatient course, (3) postoperative follow-up, and (4) postoperative final
      histopathologic findings were reviewed. For patients with synchronous thyroid
      lesions, reports of (1) thyroid evaluation and imaging and (2) preoperative (fine
      needle aspiration), (3) intraoperative (frozen section), and (4) postoperative
      (final) histopathologic results for the thyroid lesions were reviewed. MAIN
      OUTCOME MEASURES: Incidence of synchronous thyroid lesions and laryngeal cancer
      in patients undergoing OPL. RESULTS: Eight (11.9%) of 67 (95% confidence
      interval, 5.3%-22.2%) patients with laryngeal tumors who underwent OPL had
      evidence of synchronous thyroid lesions. All 8 patients had squamous cell
      carcinoma of the larynx and underwent either supracricoid or supraglottic
      laryngectomy. In these 8 patients, synchronous thyroid lesions were incidentally
      detected. Four patients had papillary thyroid carcinoma, 1 had squamous
      metaplasia, and 3 had follicular thyroid tissue that was negative for malignancy
      on final pathologic examination. In 2 patients, the thyroid lesions were detected
      preoperatively (prior to OPL); in another 2 patients, thyroid masses were
      detected intraoperatively; and in 4 patients, the thyroid disease was identified
      postoperatively on histopathologic examination of excised cervical lymph nodes.
      In 2 patients, thyroidectomy was performed as a second operation after the OPL,
      and 1 of them had transient vocal fold paralysis for 2 months. Thyroid
      ultrasonography was performed in 4 patients. In 3 patients, the ultrasonography
      was performed after the OPL final pathologic findings indicated the presence of
      metastatic thyroid disease in cervical lymph nodes. Ultrasonography revealed
      intrathyroidal lesions in all 3 patients. CONCLUSIONS: Patients with laryngeal
      tumors who will be undergoing OPL might have occult synchronous thyroid lesions.
      Thyroid surgery in patients with previous OPL may have an increased potential for
      complication owing to postsurgical changes in the central neck region. Routine
      preoperative evaluation of the thyroid gland, especially with ultrasonography, to
      screen for occult synchronous thyroid lesions is recommended for all patients
      with laryngeal tumors who will be undergoing OPL. Eradication of any thyroid
      cancer detected preoperatively by fine-needle aspiration should be performed at
      the same time as OPL. Pros and cons of total thyroidectomy for indeterminate
      thyroid nodules should be discussed with this patient population.

PMID- 17043250
TI  - The association between elevated EphB4 expression, smoking status, and advanced
      stage disease in patients with head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To examine the expression of EphB4 in tumor tissue, surrounding normal
      tissue, and metastatic lymph node in patients with head and neck squamous cell
      carcinoma (HNSCC) and to evaluate its association with disease stage and smoking.
      DESIGN: A retrospective study. SETTING: University of Southern California
      University Hospital, University of Southern California and Los Angeles County
      Medical Center, and Department of Otolaryngology-Head and Neck Surgery,
      University of Southern California, Los Angeles. PATIENTS: Forty-eight patients
      with different stages of HNSCC (I-IV) were enrolled into this study. Staging was
      based on the staging system of the American Joint Committee on Cancer. MAIN
      OUTCOME MEASURES: EphB4 expression in tumor tissue, surrounding normal tissue,
      and metastatic lymph node was evaluated by immunohistochemical analysis, Western
      blot, and real-time polymerase chain reaction. EphB4 expression was then compared
      between patients based on disease stage and smoking status. RESULTS: EphB4
      expression was detected in all tumor specimens and metastatic lymph nodes of
      patients with HNSCC, but expression levels were higher in the metastatic lymph
      nodes. There was a statistically significantly higher mean EphB4 protein
      expression and EphB4 gene amplification in patients with advanced disease (stage
      III or IV) vs patients with initial disease (stage I or II) and in smokers vs
      nonsmokers. CONCLUSIONS: Overexpression of EphB4 is associated with advanced
      stages of HNSCC as well as with patients who smoke. These data are the first to
      demonstrate the association of EphB4 with advanced stages of disease and smoking
      in HNSCC and hence provide a strong rationale for targeting EphB4 for HNSCC
      therapies.

PMID- 17043251
TI  - Lymphatic metastases to level IIb in hypopharyngeal squamous cell carcinoma.
AB  - OBJECTIVES: To evaluate the prevalence of level IIb lymph node (LN) metastasis
      and to identify potential clinical risk factors when level IIb metastatic
      diseases are present in patients with clinically node-negative (N0) and node
      positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This
      will provide a basis for determining whether this region can be excluded in
      elective or therapeutic neck dissection in patients with HPSCC. DESIGN:
      Prospective analysis of a case series. SETTING: University hospital. PATIENTS:
      Fifty patients with HPSCC who underwent surgical treatment for a primary lesion
      and simultaneous neck dissection from January 1998 to February 2004. MAIN OUTCOME
      MEASURES: The incidences and clinical risk factors for level IIb LN metastasis
      and regional recurrence according to the presence or absence of pathologic LN
      involvement in level IIb. RESULTS: A total of 93 neck dissections were analyzed
      in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were
      therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+
      necks had level IIb LN metastases. Level IIb nodal metastases were significantly
      more prevalent in N+ necks (P=.007) than in N0 necks and in the presence of other
      positive LNs (P=.01) than in the absence of other positive LNs. Of the 35
      patients with pathologic LNs, the regional recurrence rate was significantly
      higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1
      of 23]; P=.04). CONCLUSIONS: Level IIb LN pads may be preserved during elective
      neck dissection in the treatment of patients with clinically N0 necks with HPSCC.
      This area should be removed during therapeutic neck dissection in the treatment
      of clinically N+ necks.

PMID- 17043252
TI  - Cricohyoidoepiglottopexy vs near-total laryngectomy with epiglottic
      reconstruction in the treatment of early glottic carcinoma.
AB  - OBJECTIVE: To compare functional and oncological outcomes of
      cricohyoidoepiglottopexy (CHEP) and near-total laryngectomy with epiglottic
      reconstruction (NTLER) techniques in early glottic carcinoma. DESIGN: Case
      series, clinical study. SETTING: Two tertiary care referral centers. PATIENTS:
      Seventeen patients with T1b glottic squamous cell carcinoma were treated with
      CHEP and 21 were treated with NTLER. MAIN OUTCOME MEASURES: Fundamental
      frequency, maximum phonation time, maximum phonation intensity, Voice Handicap
      Index, and GRBAS (grade, roughness, breathiness, asthenia, and strain) scale were
      used to evaluate voice. Nasogastric tube removal times and late postoperative
      aspiration scales were used to evaluate swallowing ability. RESULTS: Fundamental
      frequency (P=.78), maximum phonation time (P=.44), and maximum phonation
      intensity (P=.94) measurements were not significantly different in the 2 groups.
      There was also no significant difference in mean Voice Handicap Index score
      (P=.62), mean decannulation time (P=.25), time to nasogastric tube removal
      (P=.12), or clinical grades of late postoperative aspiration (P=.87) between the
      2 groups. The mean Voice Handicap Index score was 55.58 in the CHEP group and
      52.78 in the NTLER group. According to the GBRAS scale, overall voice quality was
      moderately altered in both groups. All patients were successfully decannulated.
      In the CHEP and NTLER groups, the mean decannulation times were 27 and 20 days,
      respectively, and the nasogastric tubes were removed after an average of 23 and
      17 days. The overall (Kaplan-Meier) survival rate was 94% in the patients who
      underwent CHEP and 90% in the patients who underwent NTLER (P=.76). The disease
      free survival rates were 100% and 76% in the CHEP and NTLER groups, respectively
      (P=.07). CONCLUSIONS: Functional and oncological results appear to be similar
      with both treatment methods. If open surgery is planned, the choice between these
      procedures mainly depends on the experience and preference of the surgeon.

PMID- 17043253
TI  - Randomized controlled trial of harmonic scalpel use during thyroidectomy.
AB  - OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical
      complications of thyroidectomy when using the harmonic scalpel (HS) vs
      conventional hemostasis (CH). DESIGN: Single-blind, randomized controlled trial.
      SETTING: Department of Surgery, S. Chiara Hospital, University of Pisa, Pisa,
      Italy. PATIENTS: One hundred patients undergoing thyroidectomy. MAIN OUTCOME
      MEASURES: Postoperative pain, drainage volume, hypocalcemia, nerve injury, and
      operative time. INTERVENTION: Patients underwent total thyroidectomy in which
      either the HS or CH was used. RESULTS: We found no significant differences
      between the HS and CH groups at baseline. Postoperative pain was reduced in the
      HS group at 24 hours (mean visual analog scale score, 3.90 vs 5.30; P<.001) and
      36 hours (2.27 vs 3.95; P<.001). Drainage volume was significantly lower in the
      HS group (40.1 mL vs 75.4 mL; P<.001). Transient hypocalcemia was significantly
      lower in the HS group (5 patients [10%] vs 16 [32%]; P=.01). No patients
      experienced nerve injury or permanent hypocalcemia. Mean operative times were
      shorter in the HS group (40.0 vs 46.7 minutes, P<.001). CONCLUSIONS: Use of the
      HS may reduce postoperative pain, drainage volume, and transient hypocalcemia in
      patients undergoing thyroidectomy. Shorter operative times and improved outcomes
      might justify the cost of the HS compared with that of CH.

PMID- 17043254
TI  - In vivo optical coherence tomography of the human oral cavity and oropharynx.
AB  - Optical coherence tomography (OCT) is an evolving imaging modality that combines
      interferometry with low-coherence light to produce high-resolution tissue
      imaging. Cross-sectional in vivo images were obtained using an OCT device
      consisting of a Michelson interferometer, 1.3-microm broadband light source, and
      a handheld fiberoptic imaging probe. Image pixel resolution approached 10 microm.
      The mucosa of the oral cavity and oropharynx were examined in 41 patients during
      operative endoscopy. Optical coherence tomographic imaging was combined with
      endoscopic photography for gross and histologic image correlation. Optical
      coherence tomographic images of the oral cavity and oropharynx provided
      microanatomical information on the epithelium, basement membrane (BM), and
      supporting lamina propria (LP) of the mucosa. Normal microstructures identified
      in these tissues included an overlying keratin layer, papillae, ducts, glands,
      and blood vessels. Regions of pathologic features studied included mature scar,
      granulation tissue, mucous cysts, leukoplakia, and invasive cancer. Optical
      coherence tomographic imaging showed distinct zones of normal, altered, and
      ablated tissue microstructures for each pathologic process studied. Abnormal
      findings were directly compared with regions of normal tissue or conventional
      histopathologic features when tissue for analysis was available. This study
      provides a composite series of in vivo OCT images of the oral cavity and
      oropharynx in a variety of normal regions and pathologic states as well as
      outline future applications of OCT technology.

PMID- 17043255
TI  - Efficacy of sucralfate in the postoperative management of
      uvulopalatopharyngoplasty: a double-blind, randomized, controlled study.
AB  - OBJECTIVE: To evaluate the effectiveness of sucralfate in influencing throat
      pain, otalgia, analgesic requirement, bleeding, mucosal recovery, and incidence
      of postoperative bleeding in patients undergoing uvulopalatopharyngoplasty.
      DESIGN: A prospective double-blind randomized study. SETTING: University
      affiliated tertiary referral hospital. PARTICIPANTS: Eighty adult patients with
      obstructive sleep apnea syndrome requiring uvulopalatopharyngoplasty were
      recruited and randomly allocated into either a sucralfate treatment group or a
      control group. INTERVENTIONS: All patients underwent uvulopalatopharyngoplasty.
      Patients enrolled in the sucralfate group (n=40) were instructed to gargle the
      sucralfate suspension and then to swallow. Patients enrolled in the control group
      (n=40) were instructed to gargle placebo suspension at the same doses and
      schedule. MAIN OUTCOME MEASURES: Postoperative throat pain, otalgia, amount of
      analgesic required, degree of strength (defined as patients' general well-being
      and return to regular daily activities), percentage of mucosal covering, and
      postoperative bleeding. RESULTS: Throat pain and otalgia occurred significantly
      less often in sucralfate group, with less analgesic requirement and with rapid
      mucosal healing and early return to regular daily activities. There was no
      significant difference in episodes of postoperative bleeding between the 2 groups
      (P=.37). CONCLUSIONS: Although sucralfate therapy may not provide complete
      analgesia after uvulopalatopharyngoplasty, it may reduce the amount of analgesic
      required, thus preventing dose-related adverse effects from the analgesic agent.
      It can also significantly reduce the total number of days needed to return to
      normal daily activities (P=.41).

PMID- 17043256
TI  - Bacterial colonization of airway stents: a promoter of granulation tissue
      formation following laryngotracheal reconstruction.
AB  - OBJECTIVE: To investigate whether airway granulation, a common occurrence during
      laryngotracheal reconstructive surgery and a common cause of delays in definitive
      treatment and treatment failure, is associated with a microbial etiology. DESIGN:
      Prospective case-control study. SETTING: Tertiary referral airway reconstruction
      unit. PATIENTS: Patients who had an airway stent as part of their treatment for
      laryngotracheal stenosis. INTERVENTIONS: All airway stents were sent for
      microbiological analysis. Information about patient demographics, lesion
      characteristics, and presence of airway granulation tissue at different times
      during treatment were obtained and correlated against the microbiological
      findings from airway stents. MAIN OUTCOME MEASURES: A chi2 test was used to
      correlate airway colonization with specific pathogens and occurrence of airway
      granulation. Logistic regression analysis was used to identify independent
      microbiological predictors of airway granulation. RESULTS: Thirty-one airway
      stents were removed from 26 patients. The mean (SD) age at presentation was 42
      (18) years, and postintubation tracheal stenosis was the most common etiology.
      There were highly significant associations between stent colonization with
      Staphylococcus aureus and Pseudomonas aeruginosa and the occurrence of airway
      granulation (P<.02), and these microorganisms were independently associated with
      the risk of developing airway granulation. Furthermore, S aureus was associated
      with persistence of airway granulation on average 4 months following removal of
      the stent. CONCLUSIONS: Airway granulation seems to be associated not with
      polymicrobial airway colonization but with infection with specific pathogenic
      microorganisms. All patients undergoing laryngotracheoplasty should receive
      antibiotic prophylaxis to cover these microorganisms, and the development and use
      of antibiotic-impregnated airway stents should be explored.

PMID- 17043257
TI  - Risk factors for serious complication after uvulopalatopharyngoplasty.
AB  - OBJECTIVE: To test the hypothesis that comorbidity, performance of concurrent
      sleep apnea procedures in addition to uvulopalatopharyngoplasty, body mass index,
      apnea-hypopnea index, and lowest oxygen saturation are risk factors for serious
      perioperative complications after uvulopalatopharyngoplasty. DESIGN: Prospective
      cohort and nested case-control studies. SETTING: United States Veterans Affairs
      medical centers. PATIENTS: A prospective cohort of 3130 consecutive adult
      inpatients who underwent uvulopalatopharyngoplasty from 1991 to 2001 was
      retrospectively analyzed from the Veterans Affairs National Surgical Quality
      Improvement Program database to determine the relationship between perioperative
      complications and both concurrent procedures and medical comorbidity. A nested
      case-control analysis was conducted on 43 cases with complications and 212
      controls without complications from the cohort. Controls were matched on age,
      sex, year of operation, and concurrent surgery; this case-control analysis
      enabled the study of body mass index, apnea-hypopnea index, and lowest oxygen
      saturation, which were not available in the cohort database. Multivariate
      logistic regression measured associations between risk factors and complications,
      adjusting or controlling for age, sex, race, smoking status, year of
      uvulopalatopharyngoplasty, and presence of any concurrent procedure. MAIN OUTCOME
      MEASURE: Sixteen specific serious perioperative complications, including 30-day
      mortality. RESULTS: The cohort included 3130 veterans (97% were men aged 50+/-11
      [mean+/-SD] years). In the cohort study, comorbidity was associated with serious
      complication: the adjusted risk ratio was 1.96 (95% confidence interval, 1.16
      3.18) for each increase in American Society of Anesthesiologists class.
      Concurrent nonnasal procedures increased the risk of complication compared with
      no concurrent procedures (adjusted risk ratio, 4.94; 95% confidence interval,
      2.34-10.4). In the case-control analyses, the apnea-hypopnea index, body mass
      index, and medical comorbidity were each associated with serious complication
      after adjustment for confounding variables, but this study had insufficient power
      to determine if these risk factors were independent of each other. Concurrent
      retrolingual procedures demonstrated an independent association with complication
      after adjustment for confounders. The lowest oxygen saturation was not associated
      with serious complication. CONCLUSIONS: Apnea-hypopnea index, body mass index,
      and medical comorbidity were each associated with serious complication; however,
      the low complication rate precluded demonstration of associations independent of
      each other. Concurrent retrolingual procedures were also associated with serious
      complication, but the cumulative risk of separate retrolingual procedures is
      unknown.

PMID- 17043258
TI  - Bacteriology of chronic sinusitis and acute exacerbation of chronic sinusitis.
AB  - OBJECTIVE: To establish the microbiological characteristics of acute exacerbation
      of chronic sinusitis (AECS). SETTING: Academic medical center. PATIENTS: Thirty
      two patients with chronic sinusitis and 30 patients with AECS. MAIN OUTCOME
      MEASURE: The aerobic and anaerobic microbiology of maxillary AECS and chronic
      maxillary sinusitis. RESULTS: A total of 81 isolates (33 aerobic and 48
      anaerobic) were recovered from the 32 cases (2.5 per specimen) with chronic
      sinusitis. Aerobes alone were recovered in 8 specimens (25%), anaerobes only were
      isolated in 11 (34%), and mixed aerobes and anaerobes were recovered in 13 (41%).
      The predominant aerobic and facultative bacteria were Enterobacteriaceae and
      Staphylococcus aureus. The predominant anaerobic bacteria were Peptostreptococcus
      subspecies, Fusobacterium subspecies, anaerobic gram-negative bacilli, and
      Propionibacterium acnes. Twenty-one beta-lactamase-producing bacteria were
      recovered from 17 specimens (53%). A total of 89 isolates (40 aerobic and
      facultatives, and 49 anaerobic) were recovered from the 30 patients (3.0 per
      specimen) with AECS. Aerobes were recovered in 8 instances (27%), anaerobes only
      in 11 (37%), and mixed aerobes and anaerobes were recovered in 11 (37%). The
      predominant aerobes were Streptococcus pneumoniae, Enterobacteriaceae, and S
      aureus. The predominant anaerobes were Peptostreptococcus subspecies,
      Fusobacterium subspecies, anaerobic gram-negative bacilli, and P acnes. Thirty
      six beta-lactamase-producing bacteria were recovered from 28 specimens (53%).
      CONCLUSIONS: This study demonstrates that the organisms isolated from patients
      with AECS were predominantly anaerobic and were similar to those generally
      recovered in patients with chronic sinusitis. However, aerobic bacteria that are
      usually found in acute infections (eg, S pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis) can also emerge in some of the episodes of AECS.

PMID- 17043259
TI  - Effect of genetic background on the response to bacterial sinusitis in mice.
AB  - OBJECTIVE: To study the importance of ongoing allergen exposure and TH1/TH2
      genetic background in augmented bacterial and inflammatory responses in allergic
      and infected mice. DESIGN: BALB/c and C57BL/6 mice were made allergic to
      ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated
      intranasally with Streptococcus pneumoniae. The numbers of bacteria and
      inflammatory cells in the sinuses were determined, and nasal responsiveness to
      histamine was assessed. RESULTS: Infected BALB/c and C57BL/6 mice that received
      ongoing ovalbumin challenge following intraperitoneal sensitization showed
      significantly greater bacterial load and phagocyte level compared with the
      infected-only mice. Differences were diminished after the allergen challenge was
      stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes
      compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to
      the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number
      of bacteria 28 days after infection. CONCLUSIONS: Ongoing allergic reaction
      augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal
      hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less
      allergic inflammation and bacterial load compared with allergic and infected
      BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c
      mice, which favor a TH2 response, were less able to clear infection than C57BL/6
      mice, which favor a TH1 response. Inflammation and bacterial load are affected by
      genetic background of mice and ongoing allergen stimulation.

PMID- 17043260
TI  - Eustachian tube function in patients with eosinophilic otitis media associated
      with bronchial asthma evaluated by sonotubometry.
AB  - OBJECTIVE: To determine eustachian tube function in patients with asthma and with
      or without eosinophilic otitis media (EOM), a new middle ear disease entity with
      a highly viscous middle ear effusion containing many eosinophils and usually
      associated with bronchial asthma. One of the most important causes of otitis
      media (OM) is eustachian tube dysfunction. DESIGN: Retrospective case review.
      SETTING: A referral center. PATIENTS: Twenty patients with EOM and patients with
      asthma but without OM. MAIN OUTCOME MEASURES: We studied eustachian tube function
      using sonotubometry and a questionnaire. Sonotubometry was also performed on 13
      control patients with chronic otitis media (COM) and 7 normal controls. RESULTS:
      The tubal opening duration was significantly longer in patients with EOM than in
      patients with asthma but without OM, controls with COM, and normal controls,
      indicating the presence of patulous eustachian tubes in patients with EOM.
      Responses to the questionnaire also supported the presence of patulous eustachian
      tubes in the patients with EOM. CONCLUSIONS: The presence of a patulous
      eustachian tube may be a major cause of EOM in patients with bronchial asthma. In
      patients with asthma who have a helper T-cell 2-dominant predisposition, a
      patulous eustachian tube easily allows the entry of antigenic materials into the
      middle ear, causing eosinophil-dominant inflammation.

PMID- 17043261
TI  - Predictors of chronic suppurative otitis media in children.
AB  - OBJECTIVE: To determine which factors predict development of chronic suppurative
      otitis media (CSOM) in children. DESIGN: Case-control study, with univariate and
      multivariate logistic regression analysis applied to determine which factors
      independently predict CSOM. SUBJECTS: Prognostic factors for CSOM were identified
      in (1) 100 children with CSOM and 161 controls aged 1 to 12 years and (2) 83
      children who developed CSOM in the presence of a tympanostomy tube and 136
      children with tympanostomy tubes who did not develop CSOM. RESULTS: Independent
      predictors for CSOM were previous tympanostomy tube insertion (odds ratio [OR],
      121.4 [95% confidence interval {CI}, 38.9-379.3]); having had more than 3 upper
      respiratory tract infections in the past 6 months (OR, 12.2 [95% CI, 3.5-42.3]);
      having parents with a low education level (OR, 14.1 [95% CI, 2.9-68.6]); and
      having older siblings (OR, 4.4 [95% CI, 1.6-12.6]). Independent predictors for
      CSOM after tympanostomy tube insertion were having experienced more than 3
      episodes of otitis media in the past year (OR, 4.9 [95% CI, 2.2-11.0]; attending
      day care (OR, 3.6 [95% CI, 1.7-7.8]); and having older siblings (OR, 2.6 [95% CI,
      1.2-5.5]). CONCLUSIONS: Treatment with tympanostomy tubes is the most important
      prognostic factor for CSOM in children. In children who are being treated with
      tympanostomy tubes for persistent middle ear effusion, the most important
      prognostic factor for CSOM is a history of recurrent episodes of acute otitis
      media. This information should be taken into consideration and discussed with
      parents when considering insertion of tympanostomy tubes in children.

PMID- 17043262
TI  - Piriform sinus tracts in children.
AB  - OBJECTIVES: To describe the various presentations and management of piriform
      sinus tracts in children and to provide a treatment algorithm. DESIGN: Case
      series. SETTING: Pediatric otolaryngology service in a tertiary care setting.
      PATIENTS: Eight pediatric patients diagnosed as having a piriform sinus tract
      between 1999 and 2005. INTERVENTIONS: Patients were treated with surgical
      excision, endoscopic cauterization, or observation. MAIN OUTCOME MEASURE:
      Recurrence of neck infection. RESULTS: Three different modes of presentation were
      identified. Four patients presented primarily with an intrathyroidal abscess; 2
      presented with recurrent deep neck infections requiring repeated drainage; and 2
      presented with symptoms unrelated to the tract. Barium swallows identified the
      tracts in 5 of 8 patients, and telescopic hypopharyngoscopy identified the tracts
      in all 8 patients. Five patients were treated with complete excision of their
      tracts; 1 was treated with cauterization of the internal opening; and 2 were
      observed for symptoms related to the tracts. All 8 patients are currently
      asymptomatic. CONCLUSIONS: Piriform sinus tracts are rare. Most patients with
      tracts present with recurrent deep neck infections. Telescopic hypopharyngoscopy
      is the diagnostic modality of choice. Endoscopic cauterization is recommended as
      the initial therapy in symptomatic patients, with complete excision reserved for
      recurrences. Observation is appropriate for asymptomatic patients.

PMID- 17043263
TI  - Adenotonsillectomy for obstructive sleep apnea in obese children: effects on
      respiratory parameters and clinical outcome.
AB  - OBJECTIVE: To assess the efficacy of adenotonsillar surgery on respiratory sleep
      parameters and avoiding continuous positive airway pressure (CPAP) treatment in
      morbidly obese children with obstructive sleep apnea syndrome (OSAS). DESIGN:
      Retrospective. SETTING: Tertiary referral institution. PATIENTS: Children aged 2
      to 18 years, with a body mass index (BMI) at or higher than the 95th percentile
      (adjusted for age and sex), undergoing adenotonsillar surgery for OSAS.
      INTERVENTIONS: Adenotonsillectomy. MAIN OUTCOME MEASURES: Preoperative and
      postoperative respiratory disturbance index, oxygen saturation nadir, overall
      severity of OSAS (mild, moderate, or severe) and candidacy for CPAP treatment
      were assessed and compared. Variables such as age, severity of disease,
      adenotonsillar size, and BMI z scores were compared between responders and
      nonresponders to surgical treatment. RESULTS: A total of 19 patients with full
      preoperative and postoperative data for evaluation were identified. The median
      (SD) age was 78 months (53.3 months). The median (SD) BMI z score was 2.84
      (0.94). Eighteen patients (95%) had OSAS preoperatively to warrant CPAP
      treatment. Surgery reduced the overall median (SD) respiratory disturbance index
      from 20.7 (24.5) to 7.3 (14.9) (P<.001) and improved the median (SD) oxygen
      saturation nadir from 77.5% (16.3%) to 88.5 (13.1%) (P<.01). A total of 7
      patients (37%) were cured by surgery. Ten patients (53%) had postoperative
      disease of sufficient severity to require CPAP. Surgery obviated the need for
      further treatment in only 8 (44%) of the 18 patients with preoperative disease
      warranting CPAP. No differences were identified between responders and
      nonresponders to surgical treatment. CONCLUSIONS: Adenotonsillar surgery improves
      sleep respiratory parameters in morbidly obese children with OSAS. Most patients
      have residual OSAS requiring further treatment.

PMID- 17043264
TI  - An update in thinking about nonorganic voice disorders.
AB  - OBJECTIVE: To describe and evaluate psychosocial factors in nonorganic voice
      disorders (NVDs). Nonorganic voice disorders are presumed to be the result of
      increased muscular tension that is caused to varying extents by vocal misuse and
      emotional stress. It is therefore necessary to include both of these in the
      diagnosis and treatment of patients with voice disorders. DESIGN: Clinical
      survey. SETTING: Academic tertiary referral center. PATIENTS: To evaluate
      psychosocial factors in NVDs, a sample of 74 patients with NVDs was examined
      psychologically using the Giessen Test and Picture Frustration Test. The results
      were compared with a control group of 19 patients with an organic dysphonia
      (vocal cord paralysis). MAIN OUTCOME MEASURES: Six scales of the Giessen Test
      (social response, dominance, control, underlying mood, permeability, and social
      potency), 3 reaction types of the Picture Frustration Test (obstacle dominance,
      ego defense, and need persistence), and 3 aggression categories of the Picture
      Frustration Test (extrapunitivity, intropunitivity, and impunitivity). RESULTS:
      The most striking significant difference between the 2 groups was that in
      conflict situations, patients with NVDs sought a quick solution or expected other
      people to provide one, which prevented them from understanding the underlying
      causes of the conflict. CONCLUSIONS: Only if the psychosocial aspects are taken
      into account can patients with NVD be offered a therapy that treats the causes of
      the voice disorder. It must be decided individually whether and when a voice
      training approach or a more psychological-psychotherapeutical approach is
      preferable.

PMID- 17043265
TI  - Central auditory development in children with bilateral cochlear implants.
AB  - OBJECTIVE: To examine the time course of maturation of P1 latencies in infant
      sequential and simultaneous bilateral cochlear implant recipients. DESIGN:
      Retrospective case series. SETTING: Pediatric collaborative cochlear implant
      program. PATIENTS: Four children who received bilateral cochlear implants prior
      to age 2 years. INTERVENTION: Cortical auditory evoked potential was completed to
      determine the latency of the P1 response in 4 children with bilateral cochlear
      implants. MAIN OUTCOME MEASURES: Longitudinal development of the latency of the
      P1 cortical auditory evoked potential in children who received bilateral cochlear
      implants prior to age 2 years. RESULTS: In 2 patients who received sequential
      bilateral implants, P1 latencies recorded from the first implanted ear were
      within normal limits after 3 to 6 months of implant use. By comparison, P1
      latencies from the second implanted ear reached normal limits as early as 1 month
      after implant use. In 2 patients who received simultaneous bilateral implants, P1
      latencies from both ears were also within normal limits in a very short time
      frame (ie, by 1 month poststimulation). CONCLUSIONS: Our data suggest a high
      degree of plasticity of the central auditory pathways after early bilateral
      implantation. We find that P1 latencies provide a clinically useful biomarker of
      central auditory system development in children after cochlear implantation.

PMID- 17043266
TI  - Stored human septal chondrocyte viability analyzed by confocal microscopy.
AB  - OBJECTIVES: To analyze the effects of prolonged storage time, at warm and cold
      temperatures, on the viability of human nasal septal chondrocytes and to
      understand the implications for tissue engineering of septal cartilage. DESIGN:
      Basic science. SUBJECTS: Septal cartilage was obtained from 10 patients and
      placed in bacteriostatic isotonic sodium chloride solution. Four specimens were
      kept at 23 degrees C, and 4 were kept at 4 degrees C. The viability of the
      chondrocytes within the cartilage was assessed using confocal laser scanning
      microscopy every 5 days. The 2 other specimens were assessed for viability on the
      day of harvest. RESULTS: Viability on the day of harvest was 96%, implying
      minimal cell death from surgical trauma. After 1 week, cell survival in all
      specimens was essentially unchanged from the day of harvest. At 23 degrees C, the
      majority (54%) of cells were alive after 20 days. At 4 degrees C, 70% of cells
      survived 1 month and 38% were alive at 2 months. Qualitatively, chondrocytes died
      in a topographically uniform distribution in warm specimens, whereas cold
      specimens displayed a more irregular pattern of cell death. CONCLUSION: Septal
      chondrocytes remain viable for prolonged periods when stored in simple
      bacteriostatic isotonic sodium chloride solution, and such survival is enhanced
      by cold storage.

PMID- 17043267
TI  - Auricular seroma: a new concept, and diagnosis and management of 16 cases.

PMID- 17043268
TI  - Dural arteriovenous fistula presenting as subjective pulsatile tinnitus.

PMID- 17043269
TI  - Radiology quiz case 1. Diagnosis: supernumerary intranasal tooth.

PMID- 17043270
TI  - Radiology quiz case 2. Diagnosis: basal cell adenoma (BCA) of the minor salivary
      gland involving the left parapharyngeal space.

PMID- 17043271
TI  - Pathology quiz case 1. Diagnosis: carcinoid tumor of the middle ear.

PMID- 17043272
TI  - Pathology quiz case 2. Diagnosis: malakoplakia of the left tongue base.

PMID- 17043273
TI  - When fine-needle aspiration biopsy cannot exclude papillary thyroid cancer: a
      therapeutic dilemma.
AB  - HYPOTHESIS: Clinical or cytologic factors predictive of malignancy can be
      identified and incorporated into a treatment algorithm for patients with a fine
      needle aspiration biopsy (FNAB) specimen interpreted as "suspicious for"
      papillary thyroid cancer (PTC). DESIGN: Retrospective review of a prospectively
      maintained database. SETTING: University-affiliated tertiary care hospital.
      PATIENTS: Seven hundred thirty-eight patients with nodular thyroid disease
      evaluated between 1990 and 2004. INTERVENTIONS: Patients with an FNAB specimen
      suspicious for PTC were identified. The frequency of carcinoma was determined.
      Clinical features were reviewed. The FNAB specimens suspicious for PTC were
      examined in a blinded fashion to determine if specific cytologic features were
      important in distinguishing benign vs malignant disease. MAIN OUTCOME MEASURES:
      The presence of specific clinical and cytologic features was correlated with the
      incidence of carcinoma. A secondary outcome measure was to determine the value of
      frozen section examination in establishing the extent of thyroidectomy. RESULTS:
      Forty-five patients (7%) had an FNAB specimen suspicious for PTC; 18 (40%) of
      these patients had carcinoma. Prominent nuclear inclusions and/or grooves,
      papillary formations, and the absence of colloid were features associated with
      PTC (P<.05). No clinical features reliably identified malignant disease. Frozen
      section examination results altered treatment in 15 (56%) of 27 patients.
      CONCLUSIONS: An FNAB specimen suspicious for PTC is associated with a 40%
      incidence of carcinoma. Extensive nuclear inclusions and/or grooves, papillary
      formations, and the absence of colloid are predictive of carcinoma. Rare
      intranuclear inclusions and/or grooves alone in an otherwise benign-appearing
      specimen are uniformly associated with benign disease. Frozen section examination
      is of value in determining the extent of thyroidectomy.

PMID- 17043274
TI  - Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass
      lesions.
AB  - HYPOTHESIS: Accurate differentiation between inflammatory and neoplastic tumors
      of the pancreas remains a diagnostic dilemma for surgeons. The aim of the study
      was to assess the utility of 2 neoplastic markers, cancer antigen (CA) 19-9 and
      CA 125, in the differential diagnosis of pancreatic tumors. DESIGN: The patients
      were assigned to a malignant or benign group based on cytological and
      histological evaluation of pancreatic lesion samples. The serum from each patient
      was tested for CA 19-9 and CA 125. SETTING AND PATIENTS: One hundred ten patients
      with heterogeneous pancreatic lesions (inflammatory and malignant tumors) treated
      at a surgical department of a university hospital were analyzed. INTERVENTIONS:
      Samples for cytological and histological evaluation were taken during
      ultrasonography-guided fine-needle aspiration biopsy or open surgery. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive
      values of each test in the differential diagnosis of pancreatic tumors were
      determined. RESULTS: The sensitivity, specificity, positive predictive value, and
      negative predictive value of the CA 19-9 test were 80.8%, 89.1%, 93.7%, and
      89.2%, respectively. The sensitivity, specificity, positive predictive value, and
      negative predictive value of the CA 125 test were 60.8%, 83.3%, 88.2%, and 50.8%,
      respectively. The sensitivity and specificity of a combined evaluation of both CA
      19-9 and CA 125 tests were 87.8% and 77.8%, respectively. CONCLUSIONS: Taking
      into account the high but still limited sensitivity and specificity of the CA 19
      9 and CA 125 tests, their results in the differential diagnosis of pancreatic
      tumors should be interpreted consistently and in reference to imaging techniques
      such as ultrasonography and computed tomography.

PMID- 17043275
TI  - Part-time training in general surgery: results of a web-based survey.
AB  - HYPOTHESIS: The recent increase in female medical school enrollment and emphasis
      on lifestyle considerations for both men and women pose challenges for residency
      recruitment and retention. This study was designed to assess interest in part
      time surgical training. We hypothesized that more women than men would be
      interested in this option. DESIGN: A Web-based survey soliciting demographic
      information and opinions about training priorities was distributed to medical
      students, surgery residents, fellows, and trained surgeons. Respondents were
      asked to express on a 5-point Likert scale interest in (and deterrents to)
      substituting 1 or more years of standard residency with a shorter workweek (< 80
      hours but > 40 hours) in exchange for a proportionately overall longer length of
      training. SETTING: The survey was located on the American College of Surgeons Web
      site. PARTICIPANTS: Medical students (482), surgical residents (789), fellows
      (179), and fully trained surgeons (2858) affiliated with at least 1 of 4 major
      surgical societies. RESULTS: There were 4308 respondents (76% male). Of physician
      respondents, 9.1% had taken time out of residency for nonresearch reasons. Thirty
      six percent of female and 24% of male students agreed to increased interest in
      surgical careers if part-time training were an option (P = .005). Twenty-five
      percent of female and 13% of male residents (P<.001) expressed interest in this
      option. Prolonged training was cited as the primary deterrent. CONCLUSIONS:
      Eleven percent to 36% of total male and female respondents expressed interest in
      pursuing part-time training. Significantly more women than men favored a part
      time option.

PMID- 17043276
TI  - Treatment of elderly breast cancer patients in a community hospital setting.
AB  - HYPOTHESIS: Elderly breast cancer patients are underdiagnosed and undertreated in
      a community hospital setting. DESIGN: Retrospective study of tumor registry
      patients. SETTING: Community hospital. PATIENTS: A total of 354 breast cancer
      patients aged 70 years or older diagnosed between 1992 and 2002 were identified
      from the tumor registry. The data for 3 prospectively chosen age subgroups (aged
      70-74, 75-79, and > or =80 years) were subsequently analyzed. MAIN OUTCOME
      MEASURES: Data were collected regarding the method of detection of cancer, tumor
      characteristics and staging, type of treatment, and patient comorbidities.
      Comparisons between age subgroups were made using a likelihood ratio chi2 test.
      RESULTS: Forty-six percent of all patients presented with palpable breast cancer.
      Mammography was frequently used as an adjunct to the physical examination but was
      helpful in detecting occult disease in only 54% of all patients and 38% of
      patients older than 80 years. Although more than 70% of patients were considered
      stage I or II, complete pathologic staging was only performed in 64% of patients.
      Approximately 50% of patients were treated with breast-conservation surgery;
      however, adjuvant radiation therapy was omitted in 55% of these patients.
      Additionally, only 29% of patients with positive lymph nodes received
      chemotherapy, and 67% patients who were estrogen receptor-positive received
      adjuvant hormonal therapy. CONCLUSIONS: Older breast cancer patients are more
      likely to be diagnosed and staged clinically. Mammography is underused as a
      screening modality. While breast-conservation surgery was performed in about half
      of the patients, adjuvant radiation, chemotherapy, and hormonal therapies were
      frequently excluded.

PMID- 17043277
TI  - The therapeutic efficacy of edaravone in extensively burned rats.
AB  - BACKGROUND: Extensive burn injury leads to production of free radicals subsequent
      to massive fluid resuscitation, which in turn increases the risk of acute lung
      injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical
      scavenger, is clinically effective in improving the prognosis after cerebral
      infarction. However, the effect of edaravone against extensive burn injury has
      not been tested. Objected To evaluate whether edaravone can reduce free radical
      precursors in a 30% burn model in rats. DESIGN: Prospective, randomized
      controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male
      Wistar rats weighing 200 to 220 g. MAIN OUTCOME MEASURES: All rats (n = 10) were
      given a 30% full-thickness burn according to the Walker and Mason method.
      Immediately after the burn, edaravone was injected into the rats (n = 5)
      intraperitoneally at a dose of 9 mg/kg. One hour after burn injury, blood and
      tissue samples were collected to analyze free radical changes of serum and tissue
      malondialdehyde (MDA) and xanthine oxidase (XOD) and lung white blood cells.
      RESULTS: Statistical significance was found between nontreatment and edaravone
      treatment relative to serum MDA (mean +/- SD, 2.50 +/- 0.54 vs 1.74 +/- 0.29
      nmol/mL), serum XOD (mean +/- SD, 5.04 +/- 1.67 vs 2.26 +/- 0.83 U/L), tissue MDA
      (mean +/- SD, 1268.7 +/- 289.9 vs 569.1 +/- 135.9 nmol/mg protein), tissue XOD
      (mean +/- SD, 256.3 +/- 58.1 vs 50.96 +/- 19.60 mU/g tissue), lung white blood
      cells (mean +/- SD, 3088 +/- 1144 vs 1542 +/- 575 mU/g tissue), and lung XOD
      (mean +/- SD, 428.3 +/- 210.5 vs 81.8 +/- 36.0 nmol/mg protein). CONCLUSIONS:
      Edaravone treatment induces significant reduction of free radical precursors and
      their metabolites compared with controls in burn rats. This suggests that
      edaravone could be helpful in the clinical treatment of large burns.

PMID- 17043278
TI  - Metastatic neuroendocrine hepatic tumors: resection improves survival.
AB  - BACKGROUND: The optimal treatment for hepatic metastases from neuroendocrine
      tumors remains controversial because of the often indolent nature of these
      tumors. We sought to determine the effect of 3 major treatment modalities
      including medical therapy, hepatic artery embolization, and surgical resection,
      ablation, or both in patients with liver-only neuroendocrine metastases, with the
      hypothesis that surgical treatment is associated with improvement in survival.
      DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Patients
      with metastatic liver-only neuroendocrine tumors were identified from hospital
      records. INTERVENTIONS: Patients were subdivided into those receiving medical
      therapy, hepatic artery embolization, or surgical management. MAIN OUTCOME
      MEASURES: Effect of treatment on survival and palliation of symptoms was
      analyzed. RESULTS: From January 1996 through May 2004, 48 patients with liver
      only neuroendocrine metastases were identified (median follow-up, 20 months),
      including 36 carcinoid and 12 islet cell tumors. Seventeen patients were treated
      conservatively, which consisted of octreotide (n = 7), observation (n = 6), or
      systemic chemotherapy (n = 4). Hepatic artery embolization was performed in 18
      patients. Thirteen patients underwent surgical therapy, including anatomical
      liver resection (n = 6), ablation (n = 4), or combined resection and ablation (n
      = 3). No difference was noted in the percentage of liver involved with tumor
      between the 3 groups. An association of improved survival was noted in patients
      treated surgically, with a 3-year survival of 83% for patients treated by
      surgical resection, compared with 31% in patients treated with medical therapy or
      embolization (P = .01). No difference in palliation of symptoms was noted among
      the 3 treatment groups (P = .2). CONCLUSION: In patients with liver-only
      neuroendocrine metastases, surgical therapy using resection, ablation, or both is
      associated with improved survival.

PMID- 17043279
TI  - Selection criteria for simultaneous resection in patients with synchronous liver
      metastasis.
AB  - HYPOTHESIS: While simultaneous resection has been shown to be safe and effective
      in patients with synchronous metastasis, neoadjuvant chemotherapy followed by
      hepatectomy has gradually gained acceptance for both initially nonresectable
      metastasis and resectable metastasis. The boundary between these treatments is
      becoming unclear. We hypothesized that factors associated with colorectal cancer
      may play an important role in the prognosis of patients with synchronous
      metastasis and may be useful for identifying patients who can be expected to have
      adequate results following simultaneous resection. DESIGN: Outcome study.
      SETTING: Tertiary referral center. PATIENTS: From January 1980 to December 2002,
      187 patients underwent curative resection for synchronous liver metastasis from
      colorectal cancer. One hundred forty-two patients received simultaneous
      resection, 18 underwent staged resection, and 27 underwent delayed hepatic
      resection. Twenty-one clinicopathological factors were analyzed, and long-term
      prognosis was assessed. MAIN OUTCOME MEASURES: Prognostic factors and patient
      survival. RESULTS: There was no in-hospital death. In a multivariate analysis,
      the factors that significantly affected the prognosis of synchronous metastasis
      were 4 or more lymph node metastases around the primary cancer (P<.001) and
      multiple liver metastases (P = .003). In patients with 3 or fewer lymph node
      metastases around the primary cancer, the 5-year survival rates of those with 1,
      2 to 3, and 4 or more liver metastases were 63%, 33%, and 40%, respectively, but
      these rates were 15%, 22%, and 0%, respectively, in patients with 4 or more lymph
      node metastases around the primary cancer. CONCLUSIONS: The results support the
      application of simultaneous resection in patients with 0 to 3 colorectal lymph
      node metastases. However, in patients with 4 or more colorectal lymph node
      metastases, biological selection by neoadjuvant chemotherapy may be more
      suitable.

PMID- 17043280
TI  - Surgical site infection following bowel surgery: a retrospective analysis of 1446
      patients.
AB  - HYPOTHESIS: We sought to determine whether the administration of preoperative
      antibiotics, intraoperative transfusion of blood products, and intraoperative
      hypothermia has any impact on the incidence of postoperative surgical site
      infections (SSIs) in a heterogeneous patient population undergoing bowel surgery.
      DESIGN: Retrospective analysis. SETTING: From September through December 2002,
      data on 1472 patients undergoing bowel surgery at 31 academic medical centers in
      the United States were collected. PATIENTS: Patients were included in the
      analysis if they were older than 17 years of age and underwent any surgery
      involving the small bowel, colon, or rectum. Main Outcome Measure Postoperative
      SSI. Variables that might affect the risk for developing SSIs were analyzed using
      multivariate logistic regression analysis. RESULTS: Perioperative transfusion (P
      = .04; odds ratio, 1.64), and the presence of any infection at the time of
      surgery (P = .05; odds ratio, 2.46) were independent risk factors for SSI.
      Patients with a lower intraoperative temperature nadir had a lower risk for SSI
      (P = .05; odds ratio, 1.33), although this difference is not clinically
      significant (35.8 degrees C +/- 0.8 degrees C vs 36.0 degrees C +/- 0.9 degrees
      C, P<.05). There was a trend toward statistical significance for wound class when
      added to the multivariate model (P = .09; odds ratio, 1.41). The administration
      of antibiotics within 120 minutes prior to incision or within 120 minutes prior
      to and 120 minutes after incision had no effect on SSIs in this patient
      population. CONCLUSIONS: This study validates perioperative transfusion as an
      independent risk factor for SSI. The lack of effectiveness of perioperative
      antibiotic prophylaxis is surprising because it is discordant with the previous
      literature, and this finding needs further evaluation.

PMID- 17043281
TI  - Ethical and regulatory challenges associated with the exception from informed
      consent requirements for emergency research: from experimental design to
      institutional review board approval.
AB  - Clinical research studies conducted in emergency settings under the waiver of
      consent provision outlined in federal regulations are uncommon, yet the
      importance of such research that may result in potentially lifesaving
      interventions is indisputable. Surgeons, as well as health care professionals in
      other disciplines of medicine, should be aware of the multiple challenges facing
      them if they contemplate conducting a research trial without the prospective
      informed consent of enrolled subjects. The challenges associated with conducting
      research studies using the exception from informed consent requirements for
      emergency research are numerous, beginning with ensuring an appropriate study
      design, understanding state and federal regulations that govern such emergency
      research studies, and continuing through a complicated and sometimes arduous
      institutional review board (IRB) process that is unique to these studies. This
      article will describe the challenges encountered when implementing the exception
      from informed consent requirements for emergency research and will provide
      surgeon researchers with an understanding of the ethical controversies
      surrounding such studies.

PMID- 17043282
TI  - Methods and complications of anterior exposure of the thoracic and lumbar spine.
AB  - OBJECTIVE: To review the methods and complications of exposing the anterior
      aspects of the thoracic and lumbosacral spine. DATA SOURCES: PubMed (journals
      database of the National Library of Medicine), text books, the University
      HealthSystem Consortium Clinical Process Improvement Benchmarking Project, a
      newspaper, and the US government Healthcare Cost and Utilization Project. STUDY
      SELECTION: Descriptions of morbidity and mortality specifically related to
      anterior spine exposure depicted in both case reports and clinical series were
      used. DATA EXTRACTION: Mortality data from clinical series with more than 30
      cases were tabulated. Morbidity incidences were described. DATA SYNTHESIS: The
      frequency of anterior exposure of the spine for structural operations is steadily
      increasing. Both thoracic and lumbosacral anterior spine operations are
      associated with exposure-related complication rates of 10% to 50%. Pulmonary
      complications are frequent after thoracic exposures. Chylothorax is the most
      common of several rarer chest-exposure complications. Vascular complications,
      particularly arterial thrombosis (<1% of cases) and venous bleeding (2%-15% of
      cases), are the most frequent complications at the lumbar level. Other
      lumbosacral exposure complications include ureteral and nerve (somatic and
      sympathetic) injury. The mortality rate in anterior spine exposures is less than
      1%. CONCLUSIONS: The exposure portions of anterior spine operations result in
      numerous complications. There are fewer reported complications with endoscopic
      exposures of the anterior spine than with open exposures, although endoscopic
      exposures have been used for less complicated cases. In comparable cases, neither
      exposure nor results of endoscopic operations have proven better than operations
      done through minilaparotomy incisions. Perioperative cooperation between exposing
      and spine surgeons is necessary to enhance results in anterior spine operations.

PMID- 17043283
TI  - Groin hernia: anatomical and surgical history.
AB  - The history of surgical repair of groin hernia is a lengthy record of assorted
      techniques in search of a cure for an ailment that comes in many sizes and shapes
      and that has plagued humanity for thousands of years. Although improvements are
      still being sought and found, for several decades surgeons have had the means to
      relieve most hernia sufferers. A remaining issue is whether the wide array of
      surgical procedures can or should be whittled down to a few "standard" operations
      that are safe, effective, and cost-efficient. The history of the anatomy of groin
      hernia shows how much there was to learn and how much remains to be learned. It
      also shows how important it is for the surgeon to know and understand both the
      anatomy of the area and the formation of groin hernia.

PMID- 17043284
TI  - Image of the month. Cecal gastrointestinal stromal tumor.

PMID- 17043285
TI  - Image of the month. Mesenteric lipoma.

PMID- 17043286
TI  - Associations of HLA-C alleles with multinodular goiters.

PMID- 17043287
TI  - Wrong-site surgery.

PMID- 17043288
TI  - Futility of positron emission tomography and other modalities in the initial
      radiographic screening of patients with melanoma.

PMID- 17043289
TI  - Camptocormia in Parkinson's disease: new insights.

PMID- 17043290
TI  - Defining and quantifying coping strategies after stroke: a review.
AB  - The coping strategies that people use after a stroke may influence recovery.
      Coping measures are generally used to assess the mediating behaviour between a
      stressor (ie, disease or condition) and the physical or psychological outcome of
      an individual. This review evaluates measures that quantified coping strategies
      in studies on psychological adaptation to stroke. The main aspects of the coping
      measures reviewed were (a) conceptual basis; (b) coping domains assessed; (c)
      coping strategies used after a stroke; and (d) psychometric properties of coping
      measures used in studies assessing patients with stroke. Four databases (Medline,
      CINAHL, PsychINFO and Cochrane Systematic Reviews) were searched to identify
      studies that used a coping measure in stroke. 14 studies assessed coping
      strategies in patients after stroke. Ten different coping measures were used, and
      the studies reviewed had many limitations. Few studies provided definitions of
      "coping" and the psychometric properties of the coping measures were under
      reported. The need for future studies to more clearly define the coping process
      and to present data on the reliability and validity of the measures used is
      emphasised.

PMID- 17043291
TI  - Essential tremor: predictors of disease progression in a clinical cohort.
AB  - OBJECTIVES: To examine the utility of baseline factors to predict disease
      progression among a clinical cohort of patients diagnosed with essential tremor.
      MEASURES: Tremor Rating Scale (TRS). METHODS: A clinical series of 128
      consecutive patients diagnosed with essential tremor was included for study. 45
      (35%) patients had at least one follow-up exam (mean = 3.6 years). Baseline
      predictive factors examined included age, age at onset of symptoms, disease
      duration, sex, handedness, total tremor rating score, asymmetric tremor ratings,
      location of initial tremor onset, use of drugs for movement disorders, ETOH
      responsiveness of tremor, association of head or neck tremor, history of
      depression, familial history of essential tremor, Parkinson's disease,
      Alzheimer's disease and other movement disorders. RESULTS: On average, the TRS
      total score increased by <1 point per year before the first visit to the clinic
      and by about 2 points per year during the observed study period. The increase of
      2 points per year during the observed study period represented an approximate 12%
      annual change from the mean TRS total score at the first clinic visit.
      Significant (p<0.05) predictive factors associated with increased tremor severity
      at the initial clinic visit included older age, longer disease duration, use of
      movement disorder drugs and the presence of voice tremor (r = 0.24, 0.27, 0.25,
      0.19). The major factors associated with an increase in tremor severity from the
      initial clinic visit to the last follow up included asymmetrical tremor ratings,
      unilateral initial tremor onset and longer follow-up duration (r = 0.32, 0.31,
      0.30). Multivariate regression analysis accounted for about 17-30% of the
      variance in tremor ratings (p<0.05). CONCLUSION: Essential tremor is a slow,
      progressive disease. The rate of disease progression and the factors associated
      with disease progression may vary throughout the disease course.

PMID- 17043292
TI  - Neurological picture. Intracranial calcifications and activating mutation of the
      calcium-sensing receptor.

PMID- 17043293
TI  - Neurological picture. Production of oil in a brain abscess caused by
      Propionibacterium acnes.

PMID- 17043294
TI  - Pontomedullary sulcus infarct: a variant of lateral medullary syndrome.
AB  - With the advent of magnetic resonance imaging (MRI) technology, it is now
      possible to identify and determine the precise location of medullary infarcts.
      The lateral part of the medulla is most commonly affected by infarction.
      Classifications of lateral medullary infarcts are usually based on anatomical
      data, using rostrocaudal and dorsoventral axes to establish correlations with
      clinical symptoms. Different subtypes of lateral medullary syndrome, depending on
      location, shape and size of the infarct, have been described in the literature.
      We report a rare case of a patient presenting with an unusual clinical picture in
      relation to an infarct specifically located in the lateral part of the
      pontomedullary sulcus.

PMID- 17043296
TI  - Myotonic dystrophy: practical issues relating to assessment of strength.
AB  - BACKGROUND: Myotonic dystrophy type 1 is a slowly progressive multisystem disease
      in which skeletal muscle involvement is prominent. As novel physical and
      pharmacological treatments become available, it is crucial to be able to measure
      their efficacy accurately. METHODS: 158 consecutive patients with myotonic
      dystrophy were assessed annually in a specialist muscle clinic. Strength was
      measured using both the Medical Research Council (MRC) scale and a hand-held
      dynamometer. Dynamometer readings were obtained from 108 normal subjects
      (controls). RESULTS: The movements showing the greatest rate of change in
      strength were ankle dorsiflexion and pinch grip. Both of these showed a decline
      of only 0.06 points/year on the MRC scale. Using a hand-held dynamometer, a
      change in strength of 1.18 kgN/year for women and 1.61 kgN/year for men was
      detected. CONCLUSIONS: The MRC scale is unsuitable for detecting the small
      changes in strength seen in a slowly progressive disease such as myotonic
      dystrophy. Dynamometry provides a simple alternative that can give meaningful
      data over the duration of a typical clinical trial.

PMID- 17043295
TI  - Interleukin 10, monocytes and increased risk of early infection in ischaemic
      stroke.
AB  - BACKGROUND AND PURPOSE: The pathophysiology of stroke-associated infection (SAI)
      is uncertain. The cytokine profile and peripheral white cell response were
      assessed in patients with or without SAI. METHODS: The incidence of SAI was
      assessed in 110 patients with ischaemic stroke allocated antibiotic prophylaxis
      or placebo within 24 h of clinical onset. Peripheral white cell counts,
      interleukin (IL)6, tumour necrosis factor (TNF)alpha and IL10 were measured in
      plasma. RESULTS: 17 (15%) patients developed infection and showed time-dependent
      increases of total white cell count, neutrophils, monocytes, lymphocytes, IL6 and
      IL10, whereas TNFalpha and the TNFalpha/IL10 ratio decreased. In logistic
      regression, IL10 (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.01 to
      1.16), monocyte count (OR 1.42, 95% CI 1.08 to 1.87) and National Institute for
      Health Stroke Survey score on admission (OR 1.17, 95% CI 1.05 to 1.31) were
      independent predictors of systemic infection. CONCLUSIONS: SAI is associated with
      stroke severity, excessive IL10-mediated response and an increased number of
      circulating monocytes. These results support the finding that acute ischaemic
      brain injury triggers a blood-borne anti-inflammatory response that decreases the
      antimicrobial drive of the immune system.

PMID- 17043297
TI  - Increased cerebrospinal fluid and serum levels of S100B in first-onset
      schizophrenia are not related to a degenerative release of glial fibrillar acidic
      protein, myelin basic protein and neurone-specific enolase from glia or neurones.
AB  - OBJECTIVE: To assess levels of glial fibrillar acidic protein (GFAP), myelin
      basic protein (MBP), neurone-specific enolase (NSE) and S100B in patients with
      first-onset schizophrenia. METHOD: We investigated CSF and serum samples from 12
      patients with first-onset schizophrenia and from 17 control subjects by ELISA
      (GFAP, MBP) or immunoluminometric sandwich assays (NSE, S100B). RESULTS: Patients
      with schizophrenia had significantly higher levels of S100B in CSF (p = 0.004;
      2.73 (SD 0.80) v 1.92 (0.58) microg/l) and serum (p = 0.032; 0.09 (0.03) v 0.08
      (0.02) microg/l) in comparison with those in the matched control group. No
      diagnosis-dependent differences of protein concentration were seen for GFAP, MBP
      and NSE. DISCUSSION: Our finding of increased levels of S100B in patients with
      schizophrenia without an indication for significant glial (GFAP, MBP) or neuronal
      (NSE) damage may be interpreted as indirect evidence for increased active
      secretion of S100B during acute psychosis.

PMID- 17043299
TI  - Sturge-Weber syndrome (encephalotrigeminal or leptomeningeal angiomatosis).

PMID- 17043298
TI  - Changes in optic nerve head blood flow in children with cerebral malaria and
      acute papilloedema.
AB  - OBJECTIVE: To investigate capillary blood flow in the optic nerve head (ONH) of
      children with cerebral malaria. METHODS: Malawian children with cerebral malaria
      admitted to a paediatric research ward were examined by direct and indirect
      ophthalmoscopy. ONH blood flow was measured using laser Doppler flowmetry (LDF)
      in suitable patients. Mean blood volume and velocity were obtained from 30 to 60
      s recordings from the temporal ONH and used to calculate blood flow. These were
      compared with admission variables, funduscopic findings and disease outcomes.
      RESULTS: 45 children with cerebral malaria had LDF recordings; 6 subsequently
      died and 5 survivors had neurological sequelae. 12 (27%) had papilloedema. The
      mean microvascular blood volume was higher in patients with papilloedema (3.28 v
      2.54 arbitrary units, p = 0.002). The blood velocity correlated directly with
      haematocrit (r = 0.46, p = 0.001) and inversely with blood glucose (r = -0.49, p
      = 0.001). CONCLUSION: The increase in ONH microvascular blood volume in
      papilloedema measured by LDF is consistent with current theories of pathogenesis
      of papilloedema. LDF has potential as a tool to distinguish papilloedema from
      pseudopapilloedematous disc swellings. The relationship between blood velocity
      and haematocrit may relate to levels of sequestration in cerebral malaria.

PMID- 17043300
TI  - Reinfection with Lyme borreliosis presenting as a painful polyradiculopathy:
      Bannwarth's, Beevor's and Borrelia.

PMID- 17043301
TI  - Pigmentary macular dystrophy in spinocerebellar ataxia type 1.

PMID- 17043302
TI  - What's in a name--familial rectal pain syndrome becomes paroxysmal extreme pain
      disorder.

PMID- 17043303
TI  - Email triage for new neurological outpatient referrals: what the customers think.

PMID- 17043304
TI  - Now dear, I have a headache! Immediate improvement of cluster headaches after
      sexual activity.

PMID- 17043305
TI  - Denoising feedback loops by thresholding--a new role for microRNAs.

PMID- 17043306
TI  - Spineless provides a little backbone for dendritic morphogenesis.

PMID- 17043307
TI  - Histone H3 Lys 4 methylation: caught in a bind?

PMID- 17043308
TI  - Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter
      determines the Xist transcription program.
AB  - Initiation of X inactivation depends on the coordinated expression of the
      sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist
      promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like
      state in undifferentiated embryonic stem (ES) cells and shifts to a
      pseudoeuchromatic structure upon Tsix truncation. We further demonstrate that the
      epigenetic state of the Xist 5' region prior to differentiation predicts the
      efficiency of transcriptional machinery recruitment to the Xist promoter during
      differentiation. Our results provide mechanistic insights into the Tsix-mediated
      epigenetic regulation of Xist resulting in Xist promoter activation and
      initiation of X inactivation in differentiating ES cells.

PMID- 17043309
TI  - Identification of Sin1 as an essential TORC2 component required for complex
      formation and kinase activity.
AB  - Target of rapamycin (TOR) is an evolutionally conserved protein kinase in
      eukaryotes and a central cell growth controller. TOR exists in two distinct
      complexes, termed TORC1 and TORC2. Mammalian TORC2 has recently been shown to
      possess kinase activity toward the C-terminal hydrophobic site of Akt/PKB. Here,
      we report that Sin1 is an essential component of TORC2 but not of TORC1, and
      functions similarly to Rictor, the defining member of TORC2, in complex formation
      and kinase activity. Knockdown of Sin1decreases Akt phosphorylation in both
      Drosophila and mammalian cells and diminishes Akt function in vivo. It also
      disrupts the interaction between Rictor and mTOR. Furthermore, Sin1 is required
      for TORC2 kinase activity in vitro. Disruption of the Rictor gene in mice results
      in embryonic lethality and ablates Akt phosphorylation. These data demonstrate
      that Sin1 together with Rictor are key components of mTORC2 and play an essential
      role in Akt phosphorylation and signaling.

PMID- 17043310
TI  - Hedgehog-regulated localization of Vax2 controls eye development.
AB  - Cell fates in the optic neuroepithelium are determined by the combinational
      action of homeotic transcription factors. One of these is Vax2, a homeodomain
      protein that ventralizes the vertebrate eye field by repressing transcription of
      the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a
      function of time in eye development, and that this dynamic shuttling is an
      essential feature of retinal differentiation. We show that subcellular
      localization of Vax2 is controlled by phosphorylation of a single serine residue,
      S170, downstream from its homeodomain, and that this modification results in the
      exclusion of Vax2 from the nucleus. Phosphorylation of S170 is most probably
      mediated by protein kinase A and is antagonized by the ventralizing morphogen
      Sonic hedgehog. Expression of a nonphosphorylatable, constitutively nuclear Vax2
      protein in the chick optic vesicle results in constitutive repression of Pax6,
      and leads to the formation of an eyeless embryo. These results indicate that
      regulated changes in Vax2 localization modify the developmental competence of the
      optic neuroepithelium over time and thereby provide a mechanism for the
      sequential staging of eye development.

PMID- 17043311
TI  - Deficiency of Rbbp1/Arid4a and Rbbp1l1/Arid4b alters epigenetic modifications and
      suppresses an imprinting defect in the PWS/AS domain.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by deficiency
      of imprinted gene expression from paternal or maternal chromosome 15q11-q13,
      respectively. Genomic imprinting of the PWS/AS domain is regulated through a
      bipartite cis-acting imprinting center (PWS-IC/AS-IC) within and upstream of the
      SNRPN promoter. Here, we show that two Rb-binding protein-related genes,
      Rbbp1/Arid4a and Rbbp1l1/Arid4b, are involved in the regulation of imprinting of
      the IC. We recovered these two genes from gene trap mutagenesis selecting for
      altered expression of an Snrpn-EGFP fusion gene strategy. RBBP1/ARID4A is an Rb
      binding protein. RBBP1/ARID4A interacts with RBBP1L1/ARID4B and with the Snrpn
      promoter, implying that both are part of a protein complex. To further elucidate
      their roles on regulation of imprinting, we deleted the Rbbp1/Arid4a and
      Rbbp1l1/Arid4b genes in mice. Combined homozygous deficiency for Rbbp1/Arid4a and
      heterozygous deficiency for Rbbp1l1/Arid4b altered epigenetic modifications at
      the PWS-IC with reduced trimethylation of histone H4K20 and H3K9 and reduced DNA
      methylation, changing the maternal allele toward a more paternal epigenotype.
      Importantly, mutations of Rbbp1/Arid4a, Rbbp1l1/Arid4b, or Rb suppressed an AS
      imprinting defect caused by a mutation at the AS-IC. These data identify
      Rbbp1/Arid4a and Rbbp1l1/Arid4b as new members of epigenetic complexes regulating
      genomic imprinting at the PWS/AS domain.

PMID- 17043312
TI  - Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and
      misexpression in Cushing disease.
AB  - Negative feedback regulation of the proopiomelanocortin (POMC) gene by the
      glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo
      pituitary-adrenal axis, and it is in part exerted by trans-repression between GR
      and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the
      ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and
      that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as
      well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC
      promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone
      H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits
      promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and
      activator at the promoter and chromatin modification jointly contribute to trans
      repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1
      or HDAC2 should therefore produce Gc resistance, and we show that approximately
      50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark
      of Cushing disease, are deficient in nuclear expression of either protein. In
      addition to providing a molecular basis for Gc resistance, these deficiencies may
      also contribute to the tumorigenic process.

PMID- 17043313
TI  - Inhibition of homologous recombination by a cohesin-associated clamp complex
      recruited to the rDNA recombination enhancer.
AB  - Silencing within the yeast ribosomal DNA (rDNA) repeats protects the integrity of
      this highly repetitive array by inhibiting hyperrecombination and repressing
      transcription from foreign promoters. Using affinity purification combined with
      highly sensitive mixture mass spectrometry, we have analyzed the protein
      interaction network involved in suppressing homologous recombination within the
      rDNA locus. We show that the Net1 and Sir2 subunits of the RENT (regulator of
      nucleolar silencing and telophase exit) silencing complex, and Fob1, which
      recruits RENT to the nontranscribed spacer I (NTS1) region of rDNA, are
      physically associated with Tof2. In addition to RENT components and Fob1, Tof2
      copurified with a two-subunit complex composed of Lrs4 and Csm1. Tof2, Lrs4, and
      Csm1 are recruited to the NTS1 region by Fob1 and are specifically required for
      silencing at this rDNA region. Moreover, Lrs4 and Csm1 act synergistically with
      Sir2 to suppress unequal crossover at the rDNA and are released from the
      nucleolus during anaphase. Together with previous observations showing that Csm1
      physically associates with cohesin, these findings suggest a possible model in
      which RENT, Tof2, and Lrs4/Csm1 physically clamp rDNA to the cohesin ring,
      thereby restricting the movement of rDNA sister chromatids relative to each other
      to inhibit unequal exchange.

PMID- 17043314
TI  - Canalization of auxin flow by Aux/IAA-ARF-dependent feedback regulation of PIN
      polarity.
AB  - Plant development is characterized by a profound ability to regenerate and form
      tissues with new axes of polarity. An unsolved question concerns how the position
      within a tissue and cues from neighboring cells are integrated to specify the
      polarity of individual cells. The canalization hypothesis proposes a feedback
      effect of the phytohormone auxin on the directionality of intercellular auxin
      flow as a means to polarize tissues. Here we identify a cellular and molecular
      mechanism for canalization. Local auxin application, wounding, or auxin
      accumulation during de novo organ formation lead to rearrangements in the
      subcellular polar localization of PIN auxin transport components. This auxin
      effect on PIN polarity is cell-specific, does not depend on PIN transcription,
      and involves the Aux/IAA-ARF (indole-3-acetic acid-auxin response factor)
      signaling pathway. Our data suggest that auxin acts as polarizing cue, which
      links individual cell polarity with tissue and organ polarity through control of
      PIN polar targeting. This feedback regulation provides a conceptual framework for
      polarization during multiple regenerative and patterning processes in plants.

PMID- 17043315
TI  - Impact of intervention surveillance bias on analyses of child welfare report
      outcomes.
AB  - Two studies using data from child maltreatment intervention outcome evaluations
      were conducted examining several aspects of surveillance bias, including directly
      measuring rates of surveillance reporting, comparing characteristics of
      surveillance versus nonsurveillance reports, examining differences across service
      types and doses, and testing how ignoring versus removing surveillance reports in
      the data affects survival analysis. The net effect of surveillance bias was small
      in the studies examined. Home-visiting services were not biased more than center
      based services, and bias was not greater among intervention compared to
      prevention cases. Surveillance reports were equally as severe as nonsurveillance
      reports, failing to support the hypothesis that surveillance serves as early
      detection of less severe maltreatment. However, surveillance bias was far more
      substantial during time periods when participants were actively engaged in
      services. Therefore, the net impact of surveillance could vary with service
      engagement rates and the relative duration of service engagement and postservice
      follow-up times.

PMID- 17043316
TI  - Completing substance abuse treatment in child welfare: the role of co-occurring
      problems and primary drug of choice.
AB  - A significant number of substance-abusing parents in the child welfare system do
      not complete substance abuse treatments. Consequently, their children experience
      longer stays in substitute care settings, and the risk of the termination of
      parental rights is increased. This study identifies and determines the specific
      factors that explain the completion of substance abuse treatment for substance
      abusing caregivers in child welfare. The sample includes 871 caregivers enrolled
      in the Illinois Alcohol and Other Drug Abuse waiver demonstration. Approximately
      22% of these caregivers successfully completed all required levels of substance
      abuse treatment. The multivariate models indicate that age, employment status,
      and legal involvement were significantly associated with the likelihood of
      completing substance abuse treatment. Heroin users were significantly less likely
      to complete treatment as compared with alcohol, cocaine, and marijuana users. The
      findings are discussed in terms of policy and practice implications for public
      child welfare systems.

PMID- 17043317
TI  - Prenatal cocaine exposure and child welfare outcomes.
AB  - This study examines the relationship between prenatal cocaine exposure and child
      welfare outcomes. Seventy-six infants positive for cocaine at birth were matched
      to 76 negative infants. With prenatal care and maternal use of alcohol and
      tobacco controlled, cocaine-exposed infants had significant decrements in birth
      weight, length, head circumference, and depressed 5-min Apgar scores. This
      confirmed the health risk of prenatal cocaine exposure for the sample. Three-year
      follow-up data were obtained from the State Central Register and foster care
      records. Adjusting for prior maternal involvement with child welfare services the
      study groups did not differ in incidents of child maltreatment or foster care
      placement. These findings suggest that prenatal cocaine exposure is not a marker
      for abusive parenting. However, from the perspective of a cumulative risk model,
      the identification of cocaine-exposed infants at birth can form the starting
      point for the development of appropriate diagnostic and follow-up services for
      mother and child.

PMID- 17043318
TI  - This is my child: differences among foster parents in commitment to their young
      children.
AB  - In this study, the authors examined variables associated with foster mothers'
      level of commitment to their young foster children, who ranged in age from 5
      months to 5 years. Commitment was assessed using a semistructured interview known
      as the "This Is My Baby" interview (TIMB; Bates & Dozier, 1998). Among 84 foster
      parent-child dyads, foster mothers who had fostered more children previously
      showed lower levels of commitment than did foster mothers who had fostered fewer
      children. Commitment also was associated with child age at placement, with foster
      parents showing higher levels of commitment to children who were placed at
      younger ages than to children who were placed at older ages. Commitment predicted
      the stability of the relationship, with higher levels of commitment associated
      with a greater likelihood of adoption or long-term placement. These results
      suggest the importance of designing a child welfare system that will enhance
      caregivers' ability to commit to the children for whom they provide care.

PMID- 17043320
TI  - Service outcomes in physical and sexual abuse cases: a comparison of child
      advocacy center-based and standard services.
AB  - Child Advocacy Centers (CACs) were developed to improve on child abuse
      investigative services provided by child protective service (CPS) agencies.
      However, until very recently, there has been little research comparing CAC-based
      procedures and outcomes to those in CPS investigations not based in CACs. The
      current study tracked 76 child abuse cases that were reported to authorities and
      investigated through either a private, not-for-profit CAC or typical CPS services
      in a mid-south rural county. Comparisons between CAC and CPS cases were made in
      terms of involvement of local law enforcement in the investigation, provision of
      medical exams, abuse substantiation rates, mental health referrals, prosecution
      referrals, and conviction rates. Analyses revealed higher rates of law
      enforcement involvement, medical examinations, and case substantiation in the CAC
      based cases compared to the CPS cases. Despite limitations due to sample size and
      non-randomization, this study found preliminary support for the assumptions
      underlying the establishment of CACs.

PMID- 17043319
TI  - Adolescent girls' offending and health-risking sexual behavior: the predictive
      role of trauma.
AB  - Several studies have highlighted high levels of risk for girls who have been
      exposed to traumatic experiences, but little is known about the exact
      relationship between traumatic experiences and problems with delinquency and
      health-risking sexual behavior (e.g., precipitory and/or exacerbatory roles).
      However, numerous short- and long-term detrimental effects have been linked to
      trauma, delinquency, and health-risking sexual behavior. The utility of
      diagnostic and experiential trauma measures in predicting the greatest risk for
      poor outcomes for delinquent girls was examined in this study. Results indicate
      that the experiential measures of trauma (cumulative and composite trauma scores)
      significantly predicted adolescent offending and adolescent health-risking sexual
      behavior, whereas the diagnostic measures of trauma (full and partial diagnostic
      criteria) did not.

PMID- 17043321
TI  - Pediatrician characteristics associated with child abuse identification and
      reporting: results from a national survey of pediatricians.
AB  - Pediatrician experience with child protective services (CPS) and factors
      associated with identifying and reporting suspected child physical abuse were
      examined by a survey of members of the American Academy of Pediatrics (AAP).
      Respondents provided information about their demographics and experience,
      attitudes and practices with child abuse. They indicated their diagnosis and
      management of a child in a purposely ambiguous clinical vignette. Pediatricians
      who had received recent child abuse education were more confident in their
      ability to identify and manage child abuse. High confidence in ability to manage
      child abuse and positive attitude about domestic violence screening and value of
      anticipatory guidance predicted that pediatricians would have high suspicion that
      the child in the vignette was abused and that they would report the child to CPS.
      Future efforts to improve medical intervention in child abuse should focus on
      physician attitudes and experience, as well as cognitive factors.

PMID- 17043322
TI  - An elaboration on the distinction between controversial parenting and therapeutic
      practices versus developmentally appropriate attachment parenting: a comment on
      the APSAC Task Force report.

PMID- 17043323
TI  - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
      Disorder, and Attachment Problems.

PMID- 17043324
TI  - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
      Disorder, and Attachment Problems.

PMID- 17043325
TI  - The report of the APSAC Task Force on Attachment Therapy, Reactive Attachment
      Disorder, and Attachment Problems.

PMID- 17043327
TI  - To breathe or not to breathe: the respiratory muscles and COPD.

PMID- 17043328
TI  - Development of an in vitro model for study of the efficacy of ischemic
      preconditioning in human skeletal muscle against ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (I/R) injury causes skeletal muscle infarction and ischemic
      preconditioning (IPC) augments ischemic tolerance in animal models. To date, this
      has not been demonstrated in human skeletal muscle. This study aimed to develop
      an in vitro model to investigate the efficacy of simulated IPC in human skeletal
      muscle. Human skeletal muscle strips were equilibrated in oxygenated Krebs
      Henseleit-HEPES buffer (37 degrees C). Aerobic and reperfusion phases were
      simulated by normoxic incubation and reoxygenation, respectively. Ischemia was
      simulated by hypoxic incubation. Energy store, cell viability, and cellular
      injury were assessed using ATP, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) assays, respectively.
      Morphological integrity was assessed using electron microscopy. Studies were
      designed to test stability of the preparation (n = 5-11) under normoxic
      incubation over 24 h; the effect of 1, 2, 3, 4, or 6 h hypoxia followed by 2 h of
      reoxygenation; and the protective effect of hypoxic preconditioning (HPC; 5 min
      of hypoxia/5 min of reoxygenation) before 3 h of hypoxia/2 h of reoxygenation.
      Over 24 h of normoxic incubation, muscle strips remained physiologically intact
      as assessed by MTT, ATP, and LDH assays. After 3 h of hypoxia/2 h of
      reoxygenation, MTT reduction levels declined to 50.1 +/- 5.5% (P < 0.05). MTT
      reduction levels in HPC (82.3 +/- 10.8%) and normoxic control (81.3 +/- 10.2%)
      groups were similar and higher (P < 0.05) than the 3 h of hypoxia/2 h of
      reoxygenation group (45.2 +/- 5.8%). Ultrastructural morphology was preserved in
      normoxic and HPC groups but not in the hypoxia/reoxygenation group. This is the
      first study to characterize a stable in vitro model of human skeletal muscle and
      to demonstrate a protective effect of HPC in human skeletal muscle against
      hypoxia/reoxygenation-induced injury.

PMID- 17043329
TI  - Contralateral effects of unilateral strength training: evidence and possible
      mechanisms.
AB  - If exercises are performed to increase muscle strength on one side of the body,
      voluntary strength can increase on the contralateral side. This effect, termed
      the contralateral strength training effect, is usually measured in homologous
      muscles. Although known for over a century, most studies have not been designed
      well enough to show a definitive transfer of strength that could not be explained
      by factors such as familiarity with the testing. However, an updated meta
      analysis of 16 properly controlled studies (range 15-48 training sessions) shows
      that the size of the contralateral strength training effect is approximately 8%
      of initial strength or about half the increase in strength of the trained side.
      This estimate is similar to results of a large, randomized controlled study of
      training for the elbow flexors (contralateral effect of 7% initial strength or
      one-quarter of the effect on the trained side). This is likely to reflect
      increased motoneuron output rather than muscular adaptations, although most
      methods are insufficiently sensitive to detect small muscle contributions. Two
      classes of central mechanism are identified. One involves a "spillover" to the
      control system for the contralateral limb, and the other involves adaptations in
      the control system for the trained limb that can be accessed by the untrained
      limb. Cortical, subcortical and spinal levels are all likely to be involved in
      the "transfer," and none can be excluded with current data. Although the size of
      the effect is small and may not be clinically significant, study of the
      phenomenon provides insight into neural mechanisms associated with exercise and
      training.

PMID- 17043330
TI  - Counterpoint: the classical Guyton view that mean systemic pressure, right atrial
      pressure, and venous resistance govern venous return is not correct.

PMID- 17043333
TI  - The classical Guyton view that mean systemic pressure, right atrial pressure, and
      venous resistance govern venous return is/is not correct.

PMID- 17043334
TI  - Summaries for patients. Can antibiotics improve the symptoms of the irritable
      bowel syndrome?

PMID- 17043335
TI  - Summaries for patients. What happens to patients during the year following
      treatment for sexually transmitted infections? How well does antibiotic treatment
      work?

PMID- 17043336
TI  - Summaries for patients. Mild thyroid dysfunction is not associated with anxiety,
      depression, or cognition in the elderly.

PMID- 17043337
TI  - The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the
      irritable bowel syndrome: a randomized trial.
AB  - BACKGROUND: Alterations in gut flora may be important in the pathophysiology of
      the irritable bowel syndrome (IBS). OBJECTIVE: To determine whether the
      nonabsorbed antibiotic rifaximin is more effective than placebo in reducing
      symptoms in adults with IBS. DESIGN: Double-blind, randomized, placebo-controlled
      study. SETTING: 2 tertiary care medical centers. PARTICIPANTS: 87 patients who
      met Rome I criteria for IBS and were enrolled from December 2003 to March 2005.
      INTERVENTIONS: Participants who met enrollment criteria were randomly assigned to
      receive 400 mg of rifaximin 3 times daily for 10 days (n = 43) or placebo (n =
      44). Eighty participants completed rifaximin therapy or placebo, and follow-up
      data were available for at least 34 participants per study group at any time
      point thereafter. MEASUREMENTS: A questionnaire was administered before treatment
      and 7 days after treatment. The primary outcome was global improvement in IBS.
      Patients were then asked to keep a weekly symptom diary for 10 weeks. RESULTS:
      Over the 10 weeks of follow-up, rifaximin resulted in greater improvement in IBS
      symptoms (P = 0.020). In addition, rifaximin recipients had a lower bloating
      score after treatment. LIMITATIONS: The major limitations of the study were its
      modest sample size and short duration and that most patients were from 1 center.
      CONCLUSIONS: Rifaximin improves IBS symptoms for up to 10 weeks after the
      discontinuation of therapy.

PMID- 17043338
TI  - High incidence of new sexually transmitted infections in the year following a
      sexually transmitted infection: a case for rescreening.
AB  - BACKGROUND: Studies show 11% to 15% of women treated for Chlamydia trachomatis
      are reinfected 3 to 4 months after treatment, suggesting the need for
      rescreening. There is little information on infections among men, infections with
      Neisseria gonorrhoeae or Trichomonas vaginalis, or long-term follow-up.
      OBJECTIVE: To determine the incidence of new sexually transmitted infections
      during the year after a visit to a sexually transmitted disease (STD) clinic and
      associated risk factors. DESIGN: Secondary analysis of data from a randomized,
      controlled trial (RESPECT-2). SETTING: 3 urban STD clinics. PATIENTS: Sexually
      active patients enrolled in an HIV prevention counseling trial. MEASUREMENTS:
      Patient characteristics at the initial visit; behaviors during follow-up; and new
      infections with C. trachomatis, N. gonorrhoeae, or T. vaginalis (women only)
      detected during 4 scheduled return visits and any other interim visits. RESULTS:
      2419 persons had 8129 three-month follow-up intervals. Among 1236 women, 25.8%
      had 1 or more new infections (11.9% acquired C. trachomatis, 6.3% acquired N.
      gonorrhoeae, and 12.8% acquired T. vaginalis); among 1183 men, 14.7% had 1 or
      more new infections (9.4% acquired C. trachomatis, and 7.1% acquired N.
      gonorrhoeae). Black persons and those with sexually transmitted infections at
      baseline were at highest risk for recurrent infection (adjusted odds ratio, 2.5
      and 2.4, respectively). For persons infected at baseline, the risk for infection
      was high at 3 and 6 months (16.3 per 100 three-month intervals) and remained high
      at 9 and 12 months (12.0 per 100 three-month intervals). Most (67.2%) infections
      were diagnosed during study-related visits, and 66.2% of these patients reported
      no symptoms. LIMITATIONS: Because patients were recruited from STD clinics,
      results may not be generalizable. CONCLUSIONS: Men and women who receive
      diagnoses of C. trachomatis, N. gonorrhoeae, or T. vaginalis infections should
      return in 3 months for rescreening because they are at high risk for new
      asymptomatic sexually transmitted infections. Although single-dose therapy may
      adequately treat the infection, it often does not adequately treat the patient.

PMID- 17043339
TI  - Is subclinical thyroid dysfunction in the elderly associated with depression or
      cognitive dysfunction?
AB  - BACKGROUND: Widespread use of automated sensitive assays for thyroid hormones and
      thyroid-stimulating hormone (TSH) has increased identification of mild thyroid
      dysfunction, especially in elderly patients. The clinical significance of this
      dysfunction, however, remains uncertain, and associations with cognitive
      impairment, depression, and anxiety are unconfirmed. OBJECTIVE: To determine the
      association between mild thyroid dysfunction and cognition, depression, and
      anxiety in elderly persons. DESIGN: Cross-sectional study. Associations were
      explored through mixed-model analyses. SETTING: Primary care practices in central
      England. PATIENTS: 5865 patients 65 years of age or older with no known thyroid
      disease who were recruited from primary care registers. MEASUREMENTS: Serum TSH
      and free thyroxine (T4) were measured. Depression and anxiety were assessed by
      using the Hospital Anxiety and Depression Scale (HADS), and cognitive functioning
      was established by using the Middlesex Elderly Assessment of Mental State and the
      Folstein Mini-Mental State Examination. Comorbid conditions, medication use, and
      sociodemographic profiles were recorded. RESULTS: 295 patients met the criteria
      for subclinical thyroid dysfunction (127 were hyperthyroid, and 168 were
      hypothyroid). After confounding variables were controlled for, statistically
      significant associations were seen between anxiety (HADS score) and TSH level (P
      = 0.013) and between cognition and both TSH and free T4 levels. The magnitude of
      these associations lacked clinical relevance: A 50-mIU/L increase in the TSH
      level was associated with a 1-point reduction in the HADS anxiety score, and a 1
      point increase in the Mini-Mental State Examination score was associated with an
      increase of 50 mIU/L in the TSH level or 25 pmol/L in the free T4 level.
      LIMITATIONS: Because of the low participation rate, low prevalence of subclinical
      thyroid dysfunction, and other unidentified recruitment biases, participants may
      not be representative of the elderly population. CONCLUSIONS: After the
      confounding effects of comorbid conditions and use of medication were controlled
      for, subclinical thyroid dysfunction was not associated with depression, anxiety,
      or cognition.

PMID- 17043340
TI  - Device-associated nosocomial infections in 55 intensive care units of 8
      developing countries.
AB  - BACKGROUND: Health care-associated infections from invasive medical devices in
      the intensive care unit (ICU) are a major threat to patient safety. Most
      published studies of ICU-acquired infections have come from industrialized
      western countries. In a Centers for Disease Control and Prevention (CDC) National
      Nosocomial Infections Surveillance (NNIS) System report, the U.S. pooled mean
      rates of central venous catheter (CVC)-related bloodstream infections, ventilator
      associated pneumonia, and catheter-associated urinary tract infections were 4.0
      per 1000 CVC days, 5.4 per 1000 mechanical ventilator days, and 3.9 per Foley
      catheter days, respectively. OBJECTIVE: To ascertain the incidence of device
      associated infections in the ICUs of developing countries. DESIGN: Multicenter,
      prospective cohort surveillance of device-associated infection by using the CDC
      NNIS System definitions. SETTING: 55 ICUs of 46 hospitals in Argentina, Brazil,
      Colombia, India, Mexico, Morocco, Peru, and Turkey that are members of the
      International Nosocomial Infection Control Consortium (INICC). MEASUREMENTS:
      Rates of device-associated infection per 100 patients and per 1000 device days.
      RESULTS: During 2002-2005, 21,069 patients who were hospitalized in ICUs for an
      aggregate 137,740 days acquired 3095 device-associated infections for an overall
      rate of 14.7% or 22.5 infections per 1000 ICU days. Ventilator-associated
      pneumonia posed the greatest risk (41% of all device-associated infections or
      24.1 cases [range, 10.0 to 52.7 cases] per 1000 ventilator days), followed by CVC
      related bloodstream infections (30% of all device-associated infections or 12.5
      cases [range, 7.8 to 18.5 cases] per 1000 catheter days) and catheter-associated
      urinary tract infections (29% of all device-associated infections or 8.9 cases
      [range, 1.7 to 12.8 cases] per 1000 catheter days). Notably, 84% of
      Staphylococcus aureus infections were caused by methicillin-resistant strains,
      51% of Enterobacteriaceae isolates were resistant to ceftriaxone, and 59% of
      Pseudomonas aeruginosa isolates were resistant to fluoroquinolones. The crude
      mortality rate for patients with device-associated infections ranged from 35.2%
      (for CVC-associated bloodstream infection) to 44.9% (for ventilator-associated
      pneumonia). LIMITATIONS: These initial data are not adequate to represent any
      entire country, and likely variations in the efficiency of surveillance and
      institutional resources may have affected the rates that were detected.
      CONCLUSIONS: Device-associated infections in the ICUs of these developing
      countries pose greater threats to patient safety than in U.S. ICUs. Active
      infection control programs that perform surveillance of infection and implement
      guidelines for prevention can improve patient safety and must become a priority
      in every country.

PMID- 17043341
TI  - Graduate medical education and patient safety: a busy--and occasionally hazardous
      -intersection.
AB  - A patient admitted to a teaching hospital with a mild episode of acute
      pancreatitis initially improved, but then her condition deteriorated and she
      subsequently died. The initial deterioration probably reflected bowel
      obstruction, as shown on an abdominal radiograph that an on-call intern forgot to
      review. This diagnostic delay was compounded by poor communication that resulted
      in a medical student inserting a feeding tube--rather than a nasogastric tube--to
      decompress the bowel, followed by failure to recognize how ill the patient had
      become. The case highlights the hazards of patient handoffs as well as the
      importance of clear communication techniques and knowing when to ask for help.
      The discussion also shows the vicious circle that results when attending
      physicians fail to provide effective supervision: Not only is safety compromised
      but trainees lose the experience of being supervised. Consequently, trainees have
      no models of effective supervision on which to draw when they become supervisors.
      They then fall into the same trap as those who taught them, busying themselves
      with direct patient care and providing supervision only as time allows.

PMID- 17043342
TI  - Narrative review: reperfusion strategies for ST-segment elevation myocardial
      infarction.
AB  - Optimal treatment for ST-segment elevation myocardial infarction depends on early
      diagnosis and rapid selection of the appropriate reperfusion strategy. Primary
      percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at
      PCI-capable hospitals. For hospitals without PCI capability, there are 2
      reperfusion strategies, primary PCI and thrombolytic therapy, which are both
      supported by clinical evidence and national guidelines. Transferring patients for
      primary PCI may cause delays and requires established, proven protocols, systems,
      and networks to achieve minimal door-to-balloon times. The authors review the
      available data and present a systematic, evidence-based approach in a simple
      framework to enable noncardiovascular and cardiovascular physicians to select the
      optimal reperfusion strategy. The framework is based on available data from
      clinical trials and local circumstances from clinical practice by incorporating
      duration of symptoms (fixed ischemia time) and anticipated transport delays to a
      PCI-capable facility (incurred ischemia time).

PMID- 17043343
TI  - Update in cardiology.

PMID- 17043344
TI  - Treatment for bacterial overgrowth in the irritable bowel syndrome.

PMID- 17043345
TI  - Quality grand rounds: the case for patient safety.

PMID- 17043346
TI  - Green tea, coffee, and diabetes.

PMID- 17043347
TI  - Green tea, coffee, and diabetes.

PMID- 17043349
TI  - Green tea, coffee, and diabetes.

PMID- 17043350
TI  - Green tea, coffee, and diabetes.

PMID- 17043351
TI  - Clinicopathologic characteristics and outcome of diffuse large B-cell lymphomas
      presenting with an associated low-grade component at diagnosis.
AB  - PURPOSE: Some diffuse large B-cell lymphomas (DLBCL) present at diagnosis with
      associated morphologic features of small B-cell non-Hodgkin's lymphoma (NHL) and
      may arise from the transformation of a previously unknown indolent low-grade
      lymphoma. The characteristics and prognosis of these particular DLBCL are not
      well known. PATIENTS AND METHODS: The strict morphologic review of consecutive
      DLBCL patients diagnosed over 12 years in our department (Hematology Department,
      Centre Hospitalier Lyon-Sud, Lyon, France) allowed to retrieve 60 DLBCL that
      could be have occurred from the transformation of marginal zone B-cell NHL (32
      patients), follicular NHL (22 patients), and small lymphocytic NHL (6 patients).
      We compared them to 180 matched patients of de novo DLBCL. RESULTS: Patients
      median age was 55 years and presented the following clinical characteristics:
      poor performance status in 33%, disseminated disease in 97%, more than one
      extranodal site in 50%, and increased lactate dehydrogenase level in 55%.
      Complete remission with multidrug chemotherapy regimens was achieved in 60% of
      the patients, but 48% relapsed: 28% with aggressive and 20% with indolent
      histology, respectively. Overall survival (OS) and freedom-from-progression rates
      at 5 years were 57% and 33%, respectively. The matched-control analysis showed
      that patients with transformed NHL at diagnosis had lower complete response to
      chemotherapy (P = .004) and higher progression rate (P = .03), whereas no
      difference was observed in OS (P = .21). CONCLUSION: Compared to de novo DLBCL,
      transformed NHL at diagnosis have similar overall survival but lower complete
      response to initial treatment and higher risk of indolent relapses.

PMID- 17043352
TI  - Post-transcriptional destabilization of p21cip1 by protein kinase C in
      fibroblasts.
AB  - p21(cip1) inhibits S phase entry by binding to cyclin-cdk2 (cyclin-dependent
      kinase-2) complexes. The levels of p21(cip1) are rapidly induced after mitogenic
      stimulation of quiescent fibroblasts and then down-regulate as the cells reach
      late G(1) phase and activate cyclin E-cdk2. In this study, we have shown that
      pharmacological inhibition of protein kinase C (PKC), expression of dominant
      negative PKCdelta, or knockdown of PKCdelta with small interfering RNA elevates
      p21(cip1) protein levels in mouse embryo fibroblasts. This effect is selective,
      post-transcriptional, and proteasome-dependent but distinct from previously
      identified post-transcriptional control mechanisms involving cyclin D1 and Skp2.
      PKCdelta inhibition results in a reduced entry into S phase, and this effect is
      not detected in p21(cip1)-null cells. Thus, post-transcriptional destabilization
      of p21(cip1) appears to be a major mitogenic effect of PKCdelta in fibroblasts.

PMID- 17043353
TI  - Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin
      ligase gp78.
AB  - Insig-1 and Insig-2, closely related endoplasmic reticulum membrane proteins,
      mediate transcriptional and post-transcriptional mechanisms that assure
      cholesterol homeostasis through their sterol-induced binding to Scap (SREBP
      cleavage-activating protein) and 3-hydroxy-3-methylglutaryl coenzyme A reductase.
      Recent studies show that Insig-1 (but not Insig-2) is ubiquitinated and rapidly
      degraded when cells are depleted of sterols. Conversely, ubiquitination of Insig
      1 is blocked, and the protein is stabilized when intracellular sterols
      accumulate. Here, we report that the ubiquitin ligase gp78, which binds with much
      higher affinity to Insig-1 than Insig-2, is required for ubiquitination and
      degradation of Insig-1 in sterol-depleted cells. Sterols prevent Insig-1
      ubiquitination and degradation by displacing gp78 from Insig-1, an event that
      results from sterol-induced binding of Scap to Insig-1. In addition to providing
      a mechanism for sterol-regulated degradation of Insig-1, these results help to
      explain why Scap is subject to endoplasmic reticulum retention upon Insig-1
      binding, whereas 3-hydroxy-3-methylglutaryl coenzyme A reductase is ubiquitinated
      and degraded.

PMID- 17043354
TI  - Deletion of core fucosylation on alpha3beta1 integrin down-regulates its
      functions.
AB  - The core fucosylation (alpha1,6-fucosylation) of glycoprotein is widely
      distributed in mammalian tissues. Recently alpha1,6-fucosylation has been further
      reported to be very crucial by the study of alpha1,6-fucosyltransferase (Fut8)
      knock-out mice, which shows the phenotype of emphysema-like changes in the lung
      and severe growth retardation. In this study, we extensively investigated the
      effect of core fucosylation on alpha3beta1 integrin and found for the first time
      that Fut8 makes an important contribution to the functions of this integrin. The
      role of core fucosylation in alpha3beta1 integrin-mediated events has been
      studied by using Fut8(+/+) and Fut8(-/-) embryonic fibroblasts, respectively. We
      found that the core fucosylation of alpha3beta1 integrin, the major receptor for
      laminin 5, was abundant in Fut8(+/+) cells but was totally abolished in Fut8(-/-)
      cells, which was associated with the deficient migration mediated by alpha3beta1
      integrin in Fut8(-/-) cells. Moreover integrin-mediated cell signaling was
      reduced in Fut8(-/-) cells. The reintroduction of Fut8 potentially restored
      laminin 5-induced migration and intracellular signaling. Collectively, these
      results suggested that core fucosylation is essential for the functions of
      alpha3beta1 integrin.

PMID- 17043356
TI  - A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species
      homeostasis in Arabidopsis.
AB  - Mitogen-activated protein kinase kinase kinases (MAPKKKs) play key roles in intra
      and extracellular signaling in eukaryotes. Here we report that the MAPKKK MEKK1
      regulates redox homeostasis in Arabidopsis. We show that MEKK1-deficient plants
      are misregulated in the expression of a number of genes involved in cellular
      redox control and accumulate reactive oxygen species (ROS). Most strikingly,
      homozygous mekk1 mutant plants exhibit a lethal phenotype when developing true
      leaves. MEKK1 kinase activity and protein stability was regulated by H(2)O(2) in
      a proteasome-dependent manner and mekk1 plants were compromised in ROS-induced
      MAPK MPK4 activation. Whereas mpk3 and mpk6 knock out plants showed no defects in
      development or changes in redox control genes, mpk4 null mutant shared several
      phenotypic and transcript profile features with mekk1 plants. In agreement with
      the concept that ROS negatively regulates auxin responses in plants, mekk1 and
      mpk4 mutants show reduced expression of several auxin-inducible marker genes.
      Overall, our data defines MPK4 as downstream target of MEKK1 and show that MEKK1
      functions in integrating ROS homeostasis with plant development and hormone
      signaling.

PMID- 17043355
TI  - The tandem BRCT domain of 53BP1 is not required for its repair function.
AB  - 53BP1 plays an important role in cellular response to DNA damage. It is thought
      to be the mammalian homologue of budding yeast Rad9 and/or fission yeast Crb2.
      Rad9/Crb2 are bona fide checkpoint proteins whose activation requires their
      corresponding C-terminal tandem BRCT (BRCA1 C-terminal) motifs, which mediate
      their oligomerization and phosphorylation at multiple sites following DNA damage.
      Here we show that the function of human 53BP1 similarly depends on its
      oligomerization and phosphorylation at multiple sites but in a BRCT domain
      independent manner. Moreover, unlike its proposed yeast counterparts, human 53BP1
      only has limited checkpoint functions but rather acts as an adaptor in the repair
      of DNA double strand breaks. This difference in function may reflect the higher
      complexity of the DNA damage response network in metazoa including the evolution
      of other BRCT domain-containing proteins that may have functions redundant or
      overlapping with those of 53BP1.

PMID- 17043357
TI  - Nucleocytoplasmic shuttling of the retinoblastoma tumor suppressor protein via
      Cdk phosphorylation-dependent nuclear export.
AB  - The retinoblastoma (RB) tumor suppressor protein is a negative regulator of cell
      proliferation that is functionally inactivated in the majority of human tumors.
      Elevated Cdk activity via RB pathway mutations is observed in virtually every
      human cancer. Thus, Cdk inhibitors have tremendous promise as anticancer agents
      although detailed mechanistic knowledge of their effects on RB function is needed
      to harness their full potential. Here, we illustrate a novel function for Cdks in
      regulating the subcellular localization of RB. We present evidence of significant
      cytoplasmic mislocalization of ordinarily nuclear RB in cells harboring Cdk4
      mutations. Our findings uncover a novel mechanism to circumvent RB-mediated
      growth suppression by altered nucleocytoplasmic trafficking via the Exportin1
      pathway. Cytoplasmically mislocalized RB could be efficiently confined to the
      nucleus by inhibiting the Exportin1 pathway, reducing Cdk activity, or mutating
      the Cdk-dependent phosphorylation sites in RB that result in loss of RB-Exportin1
      association. Thus RB-mediated tumor suppression can be subverted by
      phosphorylation-dependent enhancement of nuclear export. These results support
      the notion that tumor cells can modulate the protein transport machinery thereby
      making the protein transport process a viable therapeutic target.

PMID- 17043358
TI  - Association of focal adhesion kinase with tuberous sclerosis complex 2 in the
      regulation of s6 kinase activation and cell growth.
AB  - Tuberous sclerosis complex 1 (TSC1) and TSC2 tumor suppressor proteins have been
      shown to negatively regulate cell growth through inhibition of the mammalian
      target of rapamycin (mTOR) pathway. Focal adhesion kinase (FAK) is a cytoplasmic
      tyrosine kinase that plays a critical role in integrin signaling. Here we
      identify a novel interaction between FAK and TSC2 and show that TSC2 is
      phosphorylated by FAK. Furthermore, we show that overexpression of FAK kinase
      dead mutant inhibits the phosphorylation of ribosomal S6 kinase (S6K) and
      eukaryotic initiation factor 4E-binding protein-1, two key mTOR (mammalian target
      of rapamycin) downstream targets, and negatively regulates the cell size and that
      FAK regulation of S6K phosphorylation is through TSC2. Finally, we provide data
      that FAK plays a positive role in cell adhesion-induced S6K phosphorylation,
      whereas TSC2 is required for cell suspension-induced S6K inactivation. Together,
      these results suggest that FAK might regulate S6K activation and cell size
      through its interaction with and phosphorylation of TSC2 and also provide a
      previously unappreciated role of TSC2 in the regulation of mTOR signaling by cell
      adhesion.

PMID- 17043359
TI  - Mechanism of regulation of prokaryotic tubulin-like GTPase FtsZ by membrane
      protein EzrA.
AB  - At initiation of cell division, FtsZ, a tubulin-like GTPase, assembles into a so
      called Z-ring structure at the site of division. The formation of Z ring is
      negatively regulated by EzrA, which ensures only one ring at the midcell per cell
      cycle. The mechanism leading to the negative regulation of Z-ring formation by
      EzrA has been analyzed. Our data reveal that the interaction between EzrA and
      FtsZ not only reduces the GTP-binding ability of FtsZ but also accelerates the
      rate of GTP hydrolysis, both of which are unfavorable for the polymerization of
      FtsZ. Moreover, the acceleration in rate of GTP hydrolysis by EzrA is attributed
      to stabilization of the transition state for GTP hydrolysis and reduction in the
      affinity of GDP for FtsZ. Clearly, EzrA is able to modify the GTP hydrolysis
      cycle of FtsZ. On the basis of these results, a model for how EzrA acts to
      negatively regulate Z-ring formation is proposed.

PMID- 17043360
TI  - Interactions between the RNA interference effector protein Ago1 and 14-3-3
      proteins: consequences for cell cycle progression.
AB  - The Argonaute family member Ago1 is required for formation of pericentric
      heterochromatin and small interfering RNA (siRNA)-mediated post-transcriptional
      gene silencing in the fission yeast Schizosaccharomyces pombe. In addition, we
      have recently demonstrated that Ago1 function is required for enactment of cell
      cycle checkpoints (Carmichael, J. B., Provost, P., Ekwall, K., and Hobman, T. C.
      (2004) Mol. Biol. Cell 15, 1425-1435). Here, we provide evidence that the amino
      terminus of Ago1 binds to proteins that function in cell cycle regulation
      including 14-3-3 proteins. Interestingly, the amino terminus of human Ago2, the
      endonuclease that cleaves siRNA-targeted mRNAs, was also demonstrated to bind 14
      3-3 proteins. Overexpression of the Ago1 amino terminus in yeast resulted in cell
      cycle delay at the G(2)/M boundary. Further investigation revealed that nuclear
      import of the mitosis-inducing phosphatase Cdc25 is inhibited by overexpression
      of the Ago1 amino terminus. Under these conditions, we found that the cyclin
      dependent kinase Cdc2 is constitutively phosphorylated on tyrosine 15, thereby
      reducing the activity of this kinase, a situation that delays entry into mitosis.
      We hypothesize that 14-3-3 proteins are required for Argonaute protein functions
      in cell cycle and/or gene-silencing pathways.

PMID- 17043361
TI  - Identification and stage-specific association with the translational apparatus of
      TbZFP3, a CCCH protein that promotes trypanosome life-cycle development.
AB  - The post-transcriptional control of gene expression is becoming increasingly
      important in the understanding of regulated events in eukaryotic cells. The
      parasitic kinetoplastids have a unique reliance on such processes, because their
      genome is organized into polycistronic transcription units in which adjacent
      genes are not coordinately regulated. Indeed, the number of RNA-binding proteins
      predicted to be encoded in the genome of kinetoplastids is unusually large,
      invoking the presence of unique RNA regulators dedicated to gene expression in
      these evolutionarily ancient organisms. Here, we report that a small CCCH zinc
      finger protein, TbZFP3, enhances development between life-cycle stages in
      Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both
      with the translational machinery and with other small CCCH proteins previously
      implicated in trypanosome developmental control. Antibodies to this protein also
      co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of
      insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively
      expressed, it exhibits developmentally regulated association with polyribosomes,
      and mutational analysis demonstrates that this association is essential for the
      expression of phenotype. TbZFP3 is therefore a novel regulator of developmental
      events in kinetoplastids that acts at the level of the post-transcriptional
      control of gene expression.

PMID- 17043362
TI  - Origin and goals of the "Gender Symmetry" Workshop.
AB  - This article provides a brief account of the historical background to the Gender
      Symmetry Workshop and describes its major goals. The Workshop is a successor to
      an earlier workshop co-sponsored by the Centers for Disease Control and
      Prevention and the National Institute of Justice in 1998, namely the Workshop on
      Building Data Systems for Monitoring and Responding to Violence Against Women.
      Some key issues that were left unresolved in that workshop provided the rationale
      for holding the Gender Symmetry Workshop. The Workshop was designed to cover
      three topic areas: (1) a typology of violence, (2) measurement issues, and (3)
      women's use of violence.

PMID- 17043363
TI  - Conflict and control: gender symmetry and asymmetry in domestic violence.
AB  - Four types of individual partner violence are identified based on the dyadic
      control context of the violence. In intimate terrorism, the individual is violent
      and controlling, the partner is not. In violent resistance, the individual is
      violent but not controlling; the partner is the violent and controlling one. In
      situational couple violence, although the individual is violent, neither the
      individual nor the partner is violent and controlling. In mutual violent control,
      the individual and the partner are violent and controlling. Evidence is presented
      that situational couple violence dominates in general surveys, intimate terrorism
      and violent resistance dominate in agency samples, and this is the source of
      differences across studies with respect to the gender symmetry of partner
      violence. An argument is made that if we want to understand partner violence,
      intervene effectively in individual cases, or make useful policy recommendations,
      we must make these distinctions in our research.

PMID- 17043364
TI  - Commentary on Johnson's "conflict and control: gender symmetry and asymmetry in
      domestic violence".

PMID- 17043365
TI  - The development of a theory of women's use of violence in intimate relationships.
AB  - Reports have appeared in the popular press in recent years concluding that women
      are just as violent as men. These reports stem from acontextual survey studies
      comparing prevalence rates of women's and men's physical violence. The authors
      contend that the above conclusion is simplistic and misleading, and that a
      theoretical framework that embeds women's violence in the context in which it
      occurs is sorely needed. This article proposes a model that includes women's
      violence in the context of their victimization by male partners, motivations for
      violent behavior and how they cope with relationship problems, experiences of
      childhood trauma, and outcomes of depression, anxiety, posttraumatic stress
      disorder, and substance use. The model is then examined within the context of
      gender, race, and class. The cultural context of domestic violence for African
      American and Latina women is reviewed. This literature reinforces the need to
      place women's violence in a broader sociocultural context.

PMID- 17043366
TI  - Commentary on Swan and Snow's "the development of a theory of women's use of
      violence in intimate relationships".

PMID- 17043367
TI  - Beyond frequency and severity: development and validation of the brief coercion
      and conflict scales.
AB  - Responding to calls for improved measurement in the field of domestic violence,
      this paper reports the development and initial validation of the Brief Coercion
      and Conflict Scales in a sample of incarcerated women. Confirmatory factor
      analyses tested the scales hypothesized structure and supported coercion and
      conflict as moderately and positively related but distinct constructs. Although
      women reported experiencing both conflict and coercion in their most recent
      relationship before incarceration, they reported that their experiences were more
      often marked by interpersonal conflict than by coercion. Further, the coercion
      and conflict scales differentially predicted women's behavioral and psychological
      responses to abuse. Only coercion consistently predicted strategic responses and
      posttraumatic stress symptoms. Overall, findings support the instrument as a
      viable option, but further psychometric evaluation of internal and external
      validity with additional samples is warranted.

PMID- 17043368
TI  - Commentary on Cook and Goodman's "beyond frequency and severity: development and
      validation of the brief coercion and conflict scales".

PMID- 17043369
TI  - Future directions.

PMID- 17043370
TI  - Future research on gender symmetry in physical assaults on partners.
AB  - In the light of evidence from about 200 studies showing gender symmetry in
      perpetration of partner assault, research can now focus on why gender symmetry is
      predominant and on the implications of symmetry for primary prevention and
      treatment of partner violence. Progress in such research is handicapped by a
      number of problems: (1) Insufficient empirical research and a surplus of
      discussion and theory, (2) Blinders imposed by commitment to a single causal
      factor theory-patriarchy and male dominance-in the face of overwhelming evidence
      that this is only one of a multitude of causes, (3) Research purporting to
      investigate gender differences but which obtains data on only one gender, (4)
      Denial of research grants to projects that do not assume most partner violence is
      by male perpetrators, (5) Failure to investigate primary prevention and treatment
      programs for female offenders, and (6) Suppression of evidence on female
      perpetration by both researchers and agencies.

PMID- 17043371
TI  - Increasing parasitic diseases in Japan.

PMID- 17043372
TI  - Medical check-up findings characteristic of smokers: aimed at improving smoking
      cessation interventions by physicians.
AB  - OBJECTIVE: The purpose of this study was to elucidate the medical check-up
      findings associated with smoking habit, which medical professionals, particularly
      physicians, should use for the promotion of quitting smoking. METHODS: In 6,215
      male and 1,627 female employees who participated in annual medical check-up, we
      compared the results of each test between smokers and nonsmokers. RESULTS: Many
      results were significantly different between smokers and nonsmokers in both males
      and females. Among them, the hematocrit, leukocyte count, and levels of
      hemoglobin and triglyceride were significantly higher, the level of high-density
      lipoprotein cholesterol was significantly lower, and the frequencies of positive
      urinary occult blood and hearing loss were significantly higher in male smokers
      than in male nonsmokers. Furthermore, the hematocrit, leukocyte count, positive
      urinary occult blood, hearing loss, and levels of hemoglobin, triglyceride, and
      high-density lipoprotein cholesterol showed significant trends for male
      nonsmoker, and light, moderate, and heavy male smokers, that is, significant
      associations with larger numbers of cigarettes smoked per day. CONCLUSION: Not
      only polycythemia and low high-density lipoprotein cholesterol level but also
      high leukocyte count, hearing loss, positive urinary occult blood, and high
      triglyceride level are smoking-related abnormal findings. In the medical check
      up, medical professionals should inform smokers of these data and encourage them
      to quit smoking.

PMID- 17043373
TI  - Beneficial effect of polymyxin B-immobilized fiber column (PMX) hemoperfusion
      treatment on acute exacerbation of idiopathic pulmonary fibrosis.
AB  - OBJECTIVE: This study was aimed to investigate the effect of polymyxin B
      immobilized fiber column (PMX) hemoperfusion treatment on the acute exacerbation
      of idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS: Six patients with a
      clinical diagnosis of idiopathic pulmonary fibrosis (IPF) who developed acute
      exacerbation were included in this study. Although five of six patients were
      treated with high-dose corticosteroid therapy, mechanical ventilation was
      necessary for all six patients due to severe respiratory failure. Blood endotoxin
      levels were undetectable in all patients. PMX treatment was performed on these
      six patients. RESULTS: In four of six patients, alveolar-arterial difference of
      oxygen (AaDO(2)), serum KL-6 and lactate dehydrogenase (LDH) were improved after
      PMX treatment. These four patients were successfully weaned from mechanical
      ventilation and survived more than 30 days after the initial PMX treatment.
      CONCLUSION: These data suggest a potential beneficial effect of PMX treatment on
      acute exacerbation of IPF.

PMID- 17043374
TI  - Relationship between metabolic syndrome and cigarette smoking in the Japanese
      population.
AB  - OBJECTIVE: We investigated the link between metabolic syndrome and cigarette
      smoking in the Japanese population. METHODS: A total of 3,177 Japanese subjects
      aged 20-79 years were recruited in a cross-sectional clinical investigation
      study. Habits of cigarette smoking were obtained at interviews by well-trained
      staff. The diagnosis of metabolic syndrome was based on the new criterion in
      Japan. RESULTS: Four hundred and forty men (35.3%) and 142 women (7.4%) were
      current smokers. Three hundred thirty four men (26.8%) and 69 women (3.6%) were
      diagnosed as metabolic syndrome. The prevalence of current smoker in subjects
      with metabolic syndrome was significantly higher than in subjects with non
      metabolic syndrome in men with and without adjustment for age. The prevalence of
      metabolic syndrome in men with Brinkman index > or = 600 was significantly higher
      than that in men with Brinkman index < 600. CONCLUSION: The present study
      indicated that cigarette smoking may be an important modifiable factor in
      Japanese men with metabolic syndrome.

PMID- 17043375
TI  - Cholangiocarcinoma at the cystic duct discovered by lymph node metastases with
      clear cell transformation.
AB  - We encountered a case with cholangiocarcinoma of the cystic duct, which was first
      manifested by multiple lymph node metastases with clear cell changes resembling
      clear cell adenocarcinoma (CCC). Because the clear cell changes were not
      prominent at the primary site, clear cell transformation might have occurred
      preferentially at the metastatic lesion in this case. Alternatively, tumor cells
      with clear cell transformation, found at the primary site, might have high
      metastatic potential. The patient showed thromboembolism and hypercalcemia as
      paraneoplastic syndromes at the terminal stage as reported in patients with CCC
      of the ovary. Those complications might be common biological features of CCC.

PMID- 17043377
TI  - Intractable desquamative interstitial pneumonia in a tattooed man.
AB  - A 20-year-old man with a 15 pack-year history of cigarette smoking had a tattoo
      outlined on his back with blue pigment. He noticed a dry cough and shortness of
      breath on exertion when the pigment of other colors was added at the age of 27.
      He visited our hospital two years later because of severe dyspnea. He was
      diagnosed with desquamative interstitial pneumonia by surgical lung biopsy.
      Steroid therapy with cessation of smoking was partially effective, however his
      disease worsened again and he died three and a half years after the diagnosis
      because of respiratory failure.

PMID- 17043376
TI  - Acute cerebral infarction during combination chemotherapy with s-1 and cisplatin
      for a young patient with a mucin-producing adenocarcinoma of the stomach.
AB  - We report a 29-year-old woman with gastric cancer who developed Trousseau's
      syndrome, a malignancy-related thromboembolism, during chemotherapy. She was
      diagnosed with a mucin-producing adenocarcinoma of the stomach, and chemotherapy
      with S-1 and cisplatin was commenced. During treatment, she developed a sudden
      onset of right hemiplegia. Magnetic resonance imaging showed an acute cerebral
      infarction of the left cerebral hemisphere. The underlying pathophysiology is
      thought to be chronic disseminated intravascular coagulation due to mucin
      producing adenocarcinomas. However, cisplatin-induced vascular toxicity and
      hypercoagulability caused by decreased plasma protein C activity, elevated plasma
      von-Willebrand factor levels, and hypomagnesemia has also been proposed to be
      associated with thrombogenicity.

PMID- 17043378
TI  - CD8-positive T cell-induced liver damage was found in a patient with
      polymyositis.
AB  - We describe a case of polymyositis (PM) with liver injury that occurred in a
      patient with rheumatoid arthritis (RA). A 74-year-old woman who had a 12-year
      history of RA was admitted to our hospital because of muscle weakness and liver
      dysfunction. CD8-positive T cell infiltration was found in the interstitium of
      both the liver and muscle. In addition to the administration of a large amount of
      prednisolone (PSL), high-dose intravenous immunoglobulin (IVIG) successfully
      improved myositis and hepatitis. Our case indicates the pathogenic potential of
      CD8-positive T cells in PM-associated liver injury.

PMID- 17043379
TI  - Antisynthetase syndrome associated with sarcoidosis.
AB  - A 30-year-old man complained of polyarthralgia and fatigue. The clinical findings
      and laboratory data included myositis, polyarthritis, interstitial pneumonia,
      Raynaud's phenomenon, mechanic's hand, and anti PL-7 antibody (threonyl-tRNA
      synthetase antibody). All of these signs were consistent with antisynthetase
      syndrome. His chest radiograph revealed bilateral hilar lymphadenopathy. Biopsy
      specimens from his mediastinal lymph node and muscle showed noncaseating
      epithelioid cell granulomas. Lung histology revealed nonspecific interstitial
      pneumonia. Antisynthetase syndrome associated with sarcoidosis was diagnosed.
      Interstitial pneumonia in this patient responded well to high-dose corticosteroid
      therapy.

PMID- 17043380
TI  - Acute respiratory failure associated with miliary tuberculosis successfully
      treated with sivelestat sodium hydrate.

PMID- 17043381
TI  - Superior mesenteric artery syndrome.

PMID- 17043382
TI  - Disseminated mucormycosis (zygomycosis) in acute myeloid leukemia.

PMID- 17043383
TI  - An incidentally found case of multiple localized segmented painless dissections
      of the descending aorta like gnarled tree.

PMID- 17043384
TI  - Isolation and identification of F-spondin in the boar testis and its production
      during testis growth.
AB  - F-spondin/vascular smooth muscle cell growth-promoting factor (VSGP), purified
      from the follicular fluid of adult bovine ovaries, has been identified as a
      promoter of neuronal differentiation and vascular smooth muscle growth. The
      objectives of the present study were (1) to clarify whether F-spondin is also
      produced in the testis, which is ontogenically equivalent to the ovary, and (2)
      to examine whether production of this protein changes with testicular growth. To
      isolate F-spondin from the testis, testicular homogenates obtained from 8-week
      old boars were sequentially subjected to heparin-Sepharose chromatography,
      diethylaminoethyl (DEAE)-Sepharose chromatography, and reverse-phase high
      performance liquid chromatography (RP-HPLC). The isolated protein had a molecular
      mass of approximately 110 kDa and was cross-reactive with anti-F-spondin antibody
      by Western blotting. The purified protein was further characterized by amino acid
      sequence analysis of its internal peptide. The sequence obtained was GEQCNIVPDN
      VD, and a homology search indicated that the purified protein is a homologue of
      rat, human, and bovine F-spondin. By fractionation of the same amounts of testis
      tissue obtained from 1-, 8-, 16-, and 40-week-old boars, we analyzed age-related
      production of F-spondin in the testis. Western blotting of the fractions obtained
      from RP-HPLC revealed the presence of a band at approximately 110 kDa,
      corresponding to F-spondin, in the testes obtained from boars between 1 and 16
      weeks old, but this band was not detected at 40 weeks. These results clearly
      indicate that (1) the porcine testis produces F-spondin and that (2) production
      of this protein is evident in the immature porcine testis, but not the adult
      testis.

PMID- 17043385
TI  - Differential effect of follicle-stimulating hormone and estradiol on expressions
      of vascular endothelial growth factor (VEGF) 120, VEGF164 and their receptors in
      bovine granulosa cells.
AB  - Vascular endothelial growth factor (VEGF) isoforms (VEGF 120 and VEGF 164)
      secreted by granulosa cells are involved in thecal angiogenesis during follicular
      development in the bovine ovary. However, whether the transcript of the VEGF120
      and VEGF164 isoforms differs during follicular development in the ovary is still
      unknown. We first examined the gene expression of VEGF120, VEGF164, fms-like
      tyrosine kinase (Flt-1), and fetal liver kinase (Flk-1) in the granulosa cells
      (GCs) and theca cells (TCs) of pre-selection and post-selection follicles (PRF
      and POF respectively) from the bovine ovary. Then we examined the effects of FSH
      and estradiol (E2) on these factors in cultured bovine GCs. Messenger RNA (mRNA)
      expression was quantified using real-time PCR methods. The concentrations of E2
      and P4 in the follicular fluid (FF) of the PRF and POF were estimated using an
      enzyme immunoassay (EIA). The concentrations of E2 and P4 in the FF were
      significantly higher in the POF than in the PRF. The ratio of E2/P4 in PRF and
      POF was 0.37 and 3.8, respectively. The expression levels of the VEGF120,
      VEGF164, and Flk-1 mRNAs in the GCs of POF with high E2 concentration were higher
      than those of PRF. The levels of the Flt-1 and Flk-1 mRNAs in the TCs were not
      different between PRF and POF. Since E2 in the FF of the POF used in the present
      study was high compared with the PRF, we examined the effects of E2 and FSH on
      the expression of the above genes using cultured GCs. Expression of VEGF120 mRNA
      was induced by a low concentration (1 ng/ml) of E2, whereas the levels of VEGF164
      and Flk-1 mRNAs were not affected by E2. FSH stimulated the expression of the
      VEGF isoforms and Flk-1 genes. Moreover, the expression of those genes was
      enhanced when low E2 (1 ng/ml) was added to FSH. In conclusion, our data
      indicates that the VEGF isoforms have a follicle stage-dependent expression
      pattern. Thus, our results suggest that the expression of VEGF isoforms may be
      associated with characterization of the preovulatory phenotype during follicle
      development in the bovine ovary.

PMID- 17043387
TI  - Excretion patterns of fecal progestagens, androgen and estrogens during
      pregnancy, parturition and postpartum in okapi (Okapia johnstoni).
AB  - The aim of the present study was to establish a simple method to monitor ovarian
      activity and non-invasively diagnose pregnancy in okapi (Okapia johnstoni). The
      feces of a female okapi were collected daily or every 3 days for 28 months.
      Steroids in lyophilized feces were extracted with 80% methanol, and the fecal
      levels of immunoreactive progestagens (progesterone and pregnanediol
      glucuronide), androgen (testosterone), and estrogens (estradiol-17beta and
      estrone) were determined by enzyme immunoassays with commercially available
      antisera. Using the progesterone profiles, the durations of the luteal phase,
      follicular phase, and estrous cycle were determined to be 11.1 +/- 0.4, 5.3 +/-
      0.6, and 16.5 +/- 0.7 days (n=22), respectively. Fecal levels of immunoreactive
      progesterone, pregnanediol glucuronide, and testosterone gradually increased from
      early pregnancy and peaked several months before parturition. More pregnanediol
      glucuronide was excreted in feces than progesterone during late pregnancy, but
      not during the estrous cycle. Although the fecal concentrations of immunoreactive
      estradiol-17beta and estrone change a little throughout pregnancy and non
      pregnancy, they rose sharply and temporarily on the day following parturition.
      The present study indicates that fecal assays with commercial antisera for
      progesterone and pregnanediol glucuronide are useful for evaluating luteal
      activity and diagnosing pregnancy and indicates that estrogens might have some
      role as a trigger of parturition.

PMID- 17043386
TI  - Metabolic profiles in ovulatory and anovulatory primiparous dairy cows during the
      first follicular wave postpartum.
AB  - Metabolic hormones affect ovarian function in the cow. However, the relationship
      between metabolic factors and ovarian function is not clear in the postpartum
      primiparous cow because they are still growing. The aim of the present study was
      to investigate in detail the time-dependent profile of the metabolic hormones,
      metabolites, and milk yields of ovulatory and anovulatory primiparous cows during
      the first follicular wave postpartum. We used 16 primiparous Holstein cows and
      obtained blood samples for the profiles of metabolites (glucose; non-esterified
      fatty acid, NEFA; ketone body; total cholesterol; and aspartate
      aminotransferase), metabolic hormones (growth hormone, GH; insulin-like growth
      factor-I, IGF-1; and insulin), and progesterone every other day from 1 to 21 days
      postpartum. In addition, all ovaries were observed using ultrasound. Dairy milk
      yield was recorded during the experimental period. In all cows, the first
      follicular wave postpartum was observed and 6 of the cows ovulated. The plasma
      glucose (P<0.0001) and IGF-1 (P<0.001) concentrations were lower and the plasma
      NEFA (P<0.0001) and ketone bodies (P<0.0001) concentrations and daily milk yield
      (P<0.0001) were higher in the anovulatory cows compared to the ovulatory cows.
      However, the GH levels, which enhance lipolysis for milk production, insulin and
      other metabolites did not differ between the two groups. In conclusion, the
      present study suggests that anovulation of the dominant follicle during the first
      follicular wave postpartum in primiparous cows is induced by low IGF-1 levels
      that are similar to those of multiparous cows. In addition, anovulatory cows are
      likely to mobilize body fat stores for milk production more easily than ovulatory
      cows.

PMID- 17043388
TI  - Effects of exogenous estradiol and progesterone on plasma concentrations of
      leptin in ewes in non-breeding season.
AB  - Estradiol and progesterone may play a role in controlling leptin secretion by
      utilizing their receptors in adipocytes and the genomic mechanisms of the leptin
      gene. This study was conducted to evaluate the effects of exogenous sex steroids
      on the blood leptin concentrations in ewes in the non-breeding season.
      Multiparous ewes were fed to maintenance level for their live weights. Blood
      samples were collected at 12-h intervals from Days -3 to -1 to determine the
      basal leptin levels (pre-injection period). From Day 0 to Day 5 (injection
      period), blood sampling continued at 12-h intervals, and the ewes were injected
      intramuscularly at 24-h intervals with oil, 50 mg progesterone in oil, 1 mg of
      estradiol in oil, or both steroids in oil. Leptin was measured using a sensitive
      and specific radioimmunoassay based on recombinant bovine leptin. Overall, plasma
      concentrations of leptin were not affected by any of the steroid treatments, and
      there were no differences in the value of leptin between the pre-injection and
      injection periods among the 4 groups. Therefore, the exogenous estrogen and
      progesterone used in this study do not have a strong effect on the blood leptin
      concentrations of ewes in the non-breeding season.

PMID- 17043389
TI  - Absence of radioadaptive responses in four cell-lines in vitro as determined by
      colony formation assay.
AB  - The purpose of this study was to investigate radioadaptive response in 4 cell
      lines under identical conditions using a colony assay. First, 4 cell-lines (V79,
      HeLa S3, EMT6 and SCCVII) were exposed to 8 Gy at various intervals after
      pretreatment with an adapting dose of 50 mGy or without it. Second, V79 cells
      were exposed to 8 Gy at 4.5 hrs after an adapting dose of 0 to 400 mGy. Third,
      V79 cells were exposed to 2, 4 or 6 Gy at 6 hrs after an adapting dose of 0 or 50
      mGy. In the last experiment, an adapting dose was given either immediately after
      cell plating or 24 hrs later. Cell survival was assessed by a standard colony
      assay. Adaptive response was not observed in any of the 4 lines tested. In V79
      cells, no adaptive response was seen even by changing the adapting dose,
      challenging dose, and timing of adapting radiation after cell plating. Although
      radioadaptive response has been reported for the V79 cell-line, we could not
      reproduce the result. We also failed to demonstrate the phenomenon in the other 3
      tumor cell-lines in culture.

PMID- 17043390
TI  - Double-door laminoplasty using autologous spinous process for the management of
      cervical myelopathy.
AB  - We describe a technique of double-door laminoplasty for the management of
      cervical myelopathy using the autologous spinous process instead of an artificial
      spacer. The aims in the present study were to determine the fusion rate and the
      incidence rate of breakage in the autologous spinous process, and to assess its
      efficacy for cervical laminoplasty. Twenty-three patients of cervical myelopathy
      were treated with double-door laminoplasty followed by implantation of the
      autologous spinous process. The spinous process from C3 to C7 was resected, at 8
      mm from the basal part of the spinous process. The autologous spinous process was
      made from the removed spinous process, and was implanted between each expanded
      laminae. Post-operative CT scanning determined the fusion rate between the
      expanded laminae and the autologous spinous process as 70.4% at 3 months, and
      93.5% at 6 months, after the operation. There was no dissociation and no breakage
      in the autologous spinous process during the follow-up observation period. There
      were certain advantages to our technique including the high fusion rate and good
      stability in the autologous spinous process. In addition, this technique was less
      expensive than other techniques using an artificial spacer. These findings
      indicated that this technique was a reliable procedure for effectively treating
      of cervical myelopathy which are caused by multisegmental cervical canal
      stenosis.

PMID- 17043391
TI  - Effects of systemic deep hypothermia and subarachnoid block on the longitudinally
      conducting evoked spinal cord potentials in man.
AB  - The present study reports the effects of systemic deep hypothermia (SDH) and
      subarachnoid block (SAB) on the longitudinally conducting evoked spinal cord
      potential (conducting ESCP) in man. Before induction of anesthesia, a pair of
      bipolar catheter electrodes was introduced to the epidural space: one at the
      level of the cervical enlargement and the other at the lumbosacral enlargement.
      The conducting ESCP was produced by electrical stimulation through the upper
      electrode and recorded through the lower electrode, and vice versa. SDH Study:
      Subjects were 6 patients who underwent replacement surgery of an aortic aneurysm
      with deep hypothermia anesthesia. The peak latency of the ESCP was gradually
      prolonged and the duration was widened with cooling via extracorporeal
      circulation. The amplitude of ESCP showed a biphasic change over the course of
      cooling with a turning point of around 30 degrees C in esophageal temperature.
      The ESCP was well observed until blood temperatures as low as near 10 degrees C.
      The result shows that ESCP is available as an intra-operative monitoring
      parameter of the spinal function even under SDH. SAB Study: Subjects were 7
      patients, 6 of whom had SAB and the remaining 1 intravenous application of a
      local anesthetic. The conducting ESCP was markedly depressed or disappeared
      completely even after SAB with clinical doses of various local anesthetics, while
      it was hardly affected by the intravenous application. The result implies that
      SAB causes, at least partially, the conduction block within the spinal cord.

PMID- 17043392
TI  - Comparison of preoperative fine-needle aspiration cytology diagnosis and
      histopathological diagnosis of salivary gland tumors.
AB  - We investigated 115 patients with salivary gland epithelial tumors who had
      undergone preoperative fine needle aspiration cytology (FNAC) of salivary glands
      and had been diagnosed by postoperative histopathological examination. We
      compared the findings of preoperative FNAC with their histopathological types in
      salivary gland tumors, and discuss the results and problems. The diagnostic
      accuracy, sensitivity, and specificity of preoperative FNAC of salivary glands
      were 98.2%, 88.2%, and 100%, respectively. The percentage of inadequate specimens
      was 6.1%. The rates of agreement in the diagnosis of pleomorphic adenoma, Warthin
      tumor, and basal cell adenoma were 96%, 92.9%, and 55.5%, respectively. The rate
      of agreement of histopathological types in the malignant tumors was 30%. We
      realized again not only that the diagnostic accuracy of preoperative FNAC for
      salivary gland tumors was high, but also that it was a safe, easy-to-perform,
      clinically very useful diagnostic procedure. However, this study exposed several
      problems which are the inadequate sampling rate and the difficulty in diagnosing
      malignant tumors. We have been making efforts to take appropriate specimens by
      writing comments on the cytological report indicating a re-examination, or by the
      presence of the clinical laboratory technician at the FNAC procedure. We consider
      it necessary to adequately re-aspirate the solid portion after cyst fluid
      aspiration, or to re-perform FNAC at a later date, and to improve the diagnostic
      accuracy by further experience with more patients.

PMID- 17043393
TI  - Effects of endurance training on blood lipid profiles in adolescent female
      distance runners.
AB  - The purpose of this study was to investigate the cross-sectional and longitudinal
      effects of endurance training on the relationships of body composition, blood
      lipid profiles and sex hormones in adolescent female distance-runners. We cross
      sectionally compared body composition, blood lipid profiles and blood sex
      hormones of non-athletes (n=7) and distance-runners (n=8), with the similar lower
      level of BMI (17.1 kg/m(2) vs. 18.7 kg/m(2), respectively). After the cross
      sectional comparison on the influence of endurance training, body composition,
      blood lipid profiles and blood sex hormones were examined at pre- and post-one
      year endurance training in the distance-runners (n=6) to determine longitudinal
      effects. %Fat in distance-runners revealed a tendency to be lower than that in
      non-athletes (23.8+/-3.5 vs 27.3+/-2.5%). Both groups showed good blood lipid
      profiles, such as high levels of high density lipoprotein-cholesterol (HDL-c),
      HDL-2c, and apolipoprotein A-I (ApoA-I). However, the estrogen (E(2)) level of
      distance-runners was less than one third of that in non-athletes (30.5+/-11.3 vs
      112.9+/-66.2 pg/ml, p<0.01). In addition, the blood E(2) levels (pg/ml) were
      significantly associated with the internal fat mass (IF, kg) in all subjects (r=
      0.613, p<0.05, n=15). On the other hand, the overall body composition and good
      blood lipid profiles in the longitudinal comparison were maintained to a constant
      level for one year endurance training, except for significant elevations in the
      two enzyme activities and E(2) level (LPL activity: from 145.3+/-40.8 to 362.2+/
      65.8 ng/ml, HTGL activity: from 0.054+/-0.020 to 0.173+/-0.080 micromole/ml/min,
      E(2): from 30.7+/-13.2 to 65.6+/-24.2 pg/ml, p<0.05). These results suggest that
      the lipid profiles such as HDL-c and Apo A-I in adolescent female distance
      runners could be rather affected by endurance training, despite the low level of
      E(2) for a long term.

PMID- 17043394
TI  - Significance of the " beak sign"in the differential diagnosis of uterine
      lipoleiomyoma from ovarian dermoid cyst.
AB  - A case of uterine lipoleiomyoma in a 72-year-old woman is presented. Although a
      series of imaging studies suggested a lipomatous tumor, diagnosis was difficult
      because the tumor appeared as a pedunculated mass extending from the uterine
      body. To distinguish the tumor from an ovarian lipomatous tumor, the "beak sign"
      in a magnetic resonance imaging study was diagnostic in this case. The purpose of
      this paper is to review lipomatous masses of the female pelvis, to discuss the
      differential diagnosis of the unusual imaging features, and to discuss imaging
      techniques to optimize pelvic mass characterization.

PMID- 17043395
TI  - Appearance-specific satiety increases appetite and quality of life in patients
      with metastatic liver tumor: a case report.
AB  - Loss of appetite is frequently seen and is a main factor affecting quality of
      life (QOL) in patients with advanced cancer. The etiology for loss of appetite in
      patients with cancer is multifactorial. The sensory properties of food are
      factors regulating appetite. Changes in taste, smell and texture of foods
      influence food intake. The appearance of the food is also a notable factor in
      sensory-specific satiety. We described a 46-year-old Japanese woman with multiple
      metastatic liver tumors. Although there was no obvious factor for loss of
      appetite, she suffered from a loss of appetite and subsequent malnutrition. In
      order to improve the appearance of food, we reduced the diet to 1,000 kcal/day
      from 1,500 kcal/day. On the new diet, the patient's appetite significantly
      increased and patient's nutritional status was improved. Eating whole diet was an
      important achievement and increased in mental aspects of QOL. Arrangement for the
      appearance of food may be a simple and nontoxic therapeutic strategy for patients
      with cancer suffering a loss of appetite.

PMID- 17043396
TI  - Comparative phylogeography of three Leptocarabus ground beetle species in South
      Korea, based on the mitochondrial COI and nuclear 28S rRNA genes.
AB  - We analyzed the intraspecific gene genealogies of three Leptocarabus ground
      beetle species (L. seishinensis, L. semiopacus, L. koreanus) in South Korea using
      sequence data from the mitochondrial cytochrome oxidase subunit I (COI) and
      nuclear 28S rRNA (28S) genes, and compared phylogeographical patterns among the
      species. The COI data detected significant genetic differentiation among local
      populations of all three species, whereas the 28S data showed genetic
      differentiation only for L. seishinensis. The clearest differentiation of L.
      seishinensis among local populations was between the northern and southern
      regions in the COI clades, whereas the 28S clade, which likely indicates
      relatively ancient events, revealed a range expansion across the northern and
      southern regions. Leptocarabus semiopacus had the most shallow differentiation of
      the COI haplotypes, and some clades occurred across the northern and southern
      regions. In L. koreanus, four diverged COI clades occurred in different regions,
      with partial overlaps. We discuss the difference in phylogeographical patterns
      among these Leptocarabus species, as well as between these and other groups of
      carabid beetles in South Korea.

PMID- 17043397
TI  - High levels of morphological variation despite close genetic relatedness between
      Zoanthus aff. vietnamensis and Zoanthus kuroshio (Anthozoa: Hexacorallia).
AB  - Recent investigations into the encrusting anemone genus Zoanthus using molecular
      and morphological techniques have begun to bring order to this taxonomically
      neglected group. Previous studies have confirmed the existence of three distinct
      species present in southern Japan: Z. sansibaricus, Z. kuroshio, and Z. gigantus.
      Results from such studies show species of Zoanthus to be highly morphologically
      plastic, often incorporating morphotypes with varying oral disk color and oral
      disk diameter. Literature lists the species Z. aff. vietnamensis as occurring in
      southern Japan and throughout the western Pacific Ocean, but due to the
      morphological plasticity of Zoanthus species, a re-examination of Z. aff.
      vietnamensis using molecular techniques was needed. Here, using mitochondrial 16S
      rDNA and the nuclear internal transcribed spacer of ribosomal DNA (ITS-rDNA)
      sequences, as well as morphological data, we have examined several nominal Z.
      aff. vietnamensis samples collected from Kagoshima Bay and Yakushima Island,
      Japan. Based on polyp length and diameter, oral disk diameter, mesentery and
      tentacle numbers, and colony form, Z. aff. vietnamensis is easily distinguishable
      from Z. sansibaricus, Z. kuroshio, and Z. gigantus. However, despite these clear
      morphological differences, our mitochondrial and nuclear sequence-based
      phylogenies indicate that Z. aff. vietnamensis and Z. kuroshio are very closely
      related (perhaps conspecific), highlighting the morphological plasticity of this
      genus and the difficulty of species identification based on morphological data
      alone.

PMID- 17043398
TI  - Round-trip catadromous migration in a Japanese amphipod, Sternomoera rhyaca
      (Gammaridea: Eusiridae).
AB  - We conducted a field study of the life cycle of the eusirid gammaridean amphipod
      Sternomoera rhyaca Kuribayashi, Mawatari, and Ishimaru, 1996 in a stream at
      Gokibiru, Hokkaido, Japan over the course of two non-consecutive years. This
      species is biennial; it spends most of its life in freshwater, but undertakes a
      short catadromous migration to the sea for reproduction. Reproduction occurs from
      March-June. Mature adults drift downstream to the sea singly and in precopulating
      pairs. Copulation and oviposition in the marsupium occur in mixed water at the
      stream mouth. Males die after copulation; ovigerous females return upstream by
      walking or swimming, where their eggs develop and hatch, after which the females
      also die. Juveniles remain in the stream, growing until they reach sexual
      maturity. Laboratory experiments showed that survivorship of all stages was
      lowest in seawater and highest in freshwater, though juveniles survived equally
      well in mixed water (50% seawater) and freshwater. Eggs developed to hatching
      only in freshwater; hatchlings in seawater and mixed water died within one and 21
      days, respectively. Thus, S. rhyaca is well adapted to freshwater. Indeed, the
      only stages that required elevated salinity were copulation and subsequent
      oviposition, and we speculate that freshwater inhibits the female pre
      reproductive molt. Because the life cycle of S. rhyaca has the most
      ontogenetically and temporally restricted saltwater phase known in any
      catadromous animal, its origin and maintenance are of evolutionary interest. We
      discuss two alternative hypotheses for the origin of the migratory life cycle,
      and discuss its maintenance in terms of fitness costs and benefits.

PMID- 17043399
TI  - Experience-based agonistic behavior in female crickets, Gryllus bimaculatus.
AB  - Fighting behavior in male crickets is already well described, and some of the
      mechanisms underlying aggression and aggressive motivation have already been
      revealed. Much less is known about female/female interactions. Here, we report
      that adult female crickets that had been isolated for several days readily
      entered into agonistic interactions with conspecific individuals. Characteristic
      dyadic encounters between isolated females escalated in a stepwise manner and
      were concluded with the establishment of a dominant/subordinate relationship. For
      15 to 30 minutes following an initial fight, former subordinate females showed a
      dramatic change in agonistic behavior. If they were paired with the former
      dominant opponent during this interval, a significant majority did not enter into
      any aggressive interaction but instead actively avoided the opponent. A similar
      experience-based and time-dependent increase in avoidance was observed when
      former subordinate females were paired with unfamiliar naive opponents. However,
      when faced with an unfamiliar subordinate individual in the second encounter, no
      such increase in avoidance behavior was observed. We propose that the observed
      changes in the behavior of former subordinate females are the consequence of a
      change in the general state of arousal and of the recognition of dominance
      status, but not of individual recognition. The fact that former dominant
      individuals did not show similar experience-based changes in agonistic behavior
      suggests that dominant/subordinate relationships between pairs of female crickets
      are maintained mainly by the behavior of subordinate individuals.

PMID- 17043400
TI  - Identification of a nuclear localization signal in mouse polycomb protein, M33.
AB  - The mouse Polycomb group (PcG) protein M33 forms nuclear complexes with the
      products of other PcG members and maintains repressed states of developmentally
      important genes, including homeotic genes. In this context, nuclear localization
      is a prerequisite for M33 to exert its function. However, we previously found
      that M33 in mouse liver shuttles dynamically between the nucleus and the
      cytoplasm, depending on the proliferative states of cells, coupled with
      phosphorylation and dephosphorylation of M33 protein. To understand the mechanism
      and significance of this phenomenon, we identified the functional nuclear
      localization signal (NLS) of M33 protein. Deletion mutants that lack a particular
      one of three putative NLS motifs failed to localize in the nucleus. Green
      fluorescent protein (GFP) fused to this motif specifically localized in the
      nucleus. We conclude that this amino-acid stretch in M33 acts as the functional
      NLS for this protein.

PMID- 17043401
TI  - Ultrastructure of the dermal chromatophores in a lizard (Scincidae: Plestiodon
      latiscutatus) with conspicuous body and tail coloration.
AB  - Microscopic observation of the skin of Plestiodon lizards, which have body
      stripes and blue tail coloration, identified epidermal melanophores and three
      types of dermal chromatophores: xanthophores, iridophores, and melanophores.
      There was a vertical combination of these pigment cells, with xanthophores in the
      uppermost layer, iridophores in the intermediate layer, and melanophores in the
      basal layer, which varied according to the skin coloration. Skin with yellowish
      white or brown coloration had an identical vertical order of xanthophores,
      iridophores, and melanophores, but yellowish-white skin had a thicker layer of
      iridophores and a thinner layer of melanophores than did brown skin. The
      thickness of the iridophore layer was proportional to the number of reflecting
      platelets within each iridophore. Skin showing green coloration also had three
      layers of dermal chromatophores, but the vertical order of xanthophores and
      iridophores was frequently reversed. Skin showing blue color had iridophores
      above the melanophores. In addition, the thickness of reflecting platelets in the
      blue tail was less than in yellowish-white or brown areas of the body. Skin with
      black coloration had only melanophores.

PMID- 17043402
TI  - Distribution and characterization of keratins in the epidermis of the tuatara
      (Sphenodon punctatus; Lepidosauria, Reptilia).
AB  - Reptilian scales are mainly composed of alpha-and beta-keratins. Epidermis and
      molts from adult individuals of an ancient reptilian species, the tuatara
      (Sphenodon punctatus), were analysed by immunocytochemistry, mono- and bi
      dimensional electrophoresis, and western blotting for alpha- and beta-keratins.
      The epidermis of this reptilian species with primitive anatomical traits should
      represent one of the more ancient amniotic epidermises available. Soft keratins
      (AE1- and AE3-positive) of 40-63 kDa and with isoelectric points (pI) at 4.0-6.8
      were found in molts. The AE3 antibody was diffusely localised over the
      tonofilaments of keratinocytes. The lack of basic cytokeratins may be due to
      keratin alteration in molts, following corneification or enzymatic degradation of
      keratins. Hard (beta-) keratins of 16-18 kDa and pI at 6.8, 8.0, and 9.2 were
      identified using a beta-1 antibody produced against chick scale beta-keratin. The
      antibody also labeled filaments of beta-cells and of the mature, compact beta
      layer. We have shown that beta-keratins in the tuatara resemble those of lizards
      and snakes, and that they are mainly basic proteins. These proteins replace
      cytokeratins in the pre-corneoum beta-layers, from which a hard, mechanically
      resistant corneoum layer is formed over scales. Beta-keratins may have both a
      fibrous and a matrix role in forming the hard texture of corneoum scales in this
      ancient species, as well as in more recently evolved reptiles.

PMID- 17043403
TI  - First application of X-ray refraction-based computed tomography to a biomedical
      object.
AB  - We have developed X-ray refraction-based computed tomography (CT) that is able to
      visualize soft tissue in between hard tissue. The experimental system consists of
      Si(220) diffraction double-crystals and is called the DEI (diffraction-enhanced
      imaging) method, in which the object is located between the crystals and a CCD
      camera to acquire data as 360 X-ray images. The X-ray energy used was 17.5 keV.
      The algorithm used to reconstruct CT images was developed by A. Maksimenko and
      colleagues. We successfully visualized articular cartilage and the distribution
      of bone marrow, which are inner structures. Our method has much higher contrast
      compared to the conventional absorption-based CT system.

PMID- 17043404
TI  - Light-sensitive motile iridophores and visual pigments in the neon tetra,
      Paracheirodon innesi.
AB  - Although motile iridophores in the longitudinal stripes of neon tetra skin are
      under control of the sympathetic nervous system, they also respond to light
      directly and show circadian color changes. Using neon tetra skin, we found that
      the photoresponse of iridophores depends on light intensity, and that light near
      500 nm is most effective. RT-PCR demonstrated the expression of mRNAs encoding
      rhodopsin and two kinds of cone opsins (Pi-green1 and Pi-green2) in neon tetra
      skin where the light-sensitive iridophores exist. These mRNAs are also expressed
      in the lateral eyes. The cone opsin genes, Pi-green1 and Pi-green2, show high
      similarity with the g101 and g103 genes of unique green cone opsins (belonging to
      the MWS/LWS group) of the blind Mexican cavefish. These results show that Pi
      green1, Pi-green2, and/or rhodopsin may play important roles in the photoresponse
      of neon tetra iridophores, which are most sensitive to light near 500 nm.

PMID- 17043405
TI  - Three new species of Leptolalax from Thailand (Amphibia, Anura, Megophryidae).
AB  - Three new megophryid species, Leptolalax melanoleucus, L. fuliginosus, and L.
      solus, are described from southwestern and southern Thailand on the bases of
      acoustic and morphological characteristics. Leptolalax melanoleucus and L.
      fuliginosus are similar to L. pelodytoides from northern Thailand, but differ
      from it completely in advertisement call characteristics and ventral color.
      Leptolalax solus is similar to L. heteropus from peninsular Malaysia, but differs
      from it by advertisement call, as well as by some body proportions. The
      distributional pattern of Leptolalax within Thailand is discussed.

PMID- 17043406
TI  - Biomedical issues of dietary fiber beta-glucan.
AB  - Beta-glucan is a polysaccharide in the form of fiber and the main element of
      fiber in grains such as barley, oats, yeast and mushrooms. Many studies have
      examined the efficacy of beta-glucan in terms of the lipid lowering effects,
      blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic
      effect. However, there is no comprehensive review article on the biomedical
      issues regarding beta-glucan. The authors searched for systematic reviews and
      clinical experiments for each relevant topic and reviewed the biomedical effects
      of beta-glucan, for the purpose of developing research strategies for the future.

PMID- 17043407
TI  - X-linked Opitz G/BBB syndrome: identification of a novel mutation and prenatal
      diagnosis in a Korean family.
AB  - X-linked Opitz G/BBB syndrome (XLOS; MIM 300000) is a rare multiple congenital
      anomaly disorder that is characterized by facial anomalies,
      laryngeal/tracheal/esophageal defects and genitourinary abnormalities. XLOS is
      caused by mutations in the MID1 gene which encodes a microtubule-associated RING
      Bbox-Coiled-coil (RBCC) protein. We recently found a four-year Korean male
      patient who was suspected of having XLOS. Mutation analysis of the MID1 gene in
      the patient and his mother demonstrated that the patient had a novel insertion
      mutation (c.1798_1799-insC), and his mother was a heterozygous carrier of the
      mutation. After identification of the causative mutation in this family, prenatal
      diagnosis of two consecutive fetuses were successfully undertaken. This is the
      first report on a genetically confirmed case of XLOS in Korea.

PMID- 17043408
TI  - Identification of a novel single nucleotide polymorphism of HADHA gene at a
      referred primer-binding site during pre-diagnostic tests for preimplantation
      genetic diagnosis.
AB  - The pre-diagnostic test for preimplantation genetic diagnosis (PGD) of long-chain
      3-hydroxyacyl-CoA dehydrogenase deficiency was performed by polymerase chain
      reaction (PCR) and direct sequencing for hydroxyacyl-Coenzyme A dehydrogenase/3
      ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (HADHA) gene. We obtained
      unexpected genotyping results of HADHA gene by allele drop-out in the analysis of
      patients' genomic DNA samples with a referred PCR primer set. Upon further
      analysis with a re-designed primer set, we found a novel single nucleotide
      polymorphism (SNP) at the referred primer-binding site in the normal allele of
      HADHA gene (NT_022184, 5233296 a>t). We found that the frequency of this novel
      SNP was 0.064 in Korean population. Pre-diagnostic test using single lymphocytes
      and clinical PGD were successfully performed with the re-designed primer set.
      Nineteen embryos (95.0%) among 20 were successfully diagnosed to 5 homozygous
      mutated, 8 heterozygous carrier and 6 wild type. Among 6 normal embryos, well
      developed and selected 4 embryos were transferred into the mother's uterus, but a
      pregnancy was not achieved. We proposed that an unknown SNP at primer-binding
      sites would be a major cause of allele drop-out in the PGD for single gene dis
      order.

PMID- 17043409
TI  - A Korean female patient with thiamine-responsive pyruvate dehydrogenase complex
      deficiency due to a novel point mutation (Y161C)in the PDHA1 gene.
AB  - Pyruvate dehydrogenase complex (PDHC) deficiency is mostly due to mutations in
      the X-linked E1alpha subunit gene (PDHA1). Some of the patients with PDHC
      deficiency showed clinical improvements with thiamine treatment. We report the
      results of biochemical and molecular analysis in a female patient with lactic
      acidemia. The PDHC activity was assayed at different concentrations of thiamine
      pyrophosphate (TPP). The PDHC activity showed null activity at low TPP
      concentration (1 x 10(-3) mM), but significantly increased at a high TPP
      concentration (1 mM). Sequencing analysis of PDHA1 gene of the patient revealed a
      substitution of cysteine for tyrosine at position 161 (Y161C). Thiamine treatment
      resulted in reduction of the patient's serum lactate concentration and dramatic
      clinical improvement. Biochemical, molecular, and clinical data suggest that this
      patient has a thiamine-responsive PDHC deficiency due to a novel mutation, Y161C.
      Therefore, to detect the thiamine responsiveness it is necessary to measure
      activities of PDHC not only at high but also at low concentration of TPP.

PMID- 17043410
TI  - Changes of serum cytokines after the long term immunotherapy with Japanese hop
      pollen extracts.
AB  - Japanese hop (Hop J) pollen has been considered as one of the major causative
      pollen allergens in the autumn season. We developed a new Hop J immunotherapy
      extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated
      immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with
      rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were
      collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum
      specific IgE, IgG1, and IgG4 levels to Hop J pollen extracts and serum IL-10, IL
      12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity
      and airway hyper-responsiveness to methacholine were improved during the study
      period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and
      specific IgG4 levels increased progressively (p<0.05, respectively), whereas
      total and specific IgE levels showed variable responses with no statistical
      significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during
      first year and then further decreased during next two years with statistical
      significances. (p<0.05, respectively). In conclusion, these findings suggested
      the favorable effect of long term immunotherapy with Hop J pollen extracts can be
      explained by lowered IgE affinity and generation of specific IgG4, which may be
      mediated by IL-10 and TGF-beta1.

PMID- 17043411
TI  - Body mass index and C-reactive protein in the healthy Korean aged men.
AB  - The purpose of this study was to determine the relationship between plasma C
      reactive protein (CRP) and body mass index (BMI) in elderly Korean men. A review
      of routine health examination records were done. Out of 671 eligible elderly men,
      who had their routine health examination in 2001 at a Health Promotion Center of
      a university hospital, 367 subjects were included after excluding inflammatory
      conditions. Subgroup analyses were performed on those who did not smoke and
      exercised regularly. Body composition, blood pressure, blood samples and
      radiologic examinations including chest radiography and abdominal ultrasound were
      obtained from each subject. Age, BMI, current smoking, regular exercise, WBC
      count, HDL-cholesterol, gamma glutamyl transferase were independently associated
      with logCRP. BMI subgroups according to the Asia-Pacific guideline did not show
      any difference in CRP level from each other by ANCOVA (p>0.05). However, BMI
      groups subdivided according to our criteria showed an association with CRP; the
      CRP level was lowest in the group of BMI between 18.5-19.4 and showed significant
      difference from BMI group of the highest BMI group (>or=29.0). Since elevated CRP
      levels are associated with higher risk for cardiovascular disease, lower BMI
      (18.5-19.4) levels may be advised for healthy elderly men in Korea.

PMID- 17043412
TI  - Community-acquired versus nosocomial Klebsiella pneumoniae bacteremia: clinical
      features, treatment outcomes, and clinical implication of antimicrobial
      resistance.
AB  - We conducted this study to compare clinical features, outcomes, and clinical
      implication of antimicrobial resistance in Klebsiella pneumoniae bacteremia
      acquired as community vs. nosocomial infection. A total of 377 patients with K.
      pneumoniae bacteremia (191 community-acquired and 186 nosocomial) were
      retrospectively analyzed. Neoplastic diseases (hematologic malignancy and solid
      tumor, 56%) were the most commonly associated conditions in patients with
      nosocomial bacteremia, whereas chronic liver disease (35%) and diabetes mellitus
      (20%) were the most commonly associated conditions in patients with community
      acquired bacteremia. Bacteremic liver abscess occurred almost exclusively in
      patients with community-acquired infection. The overall 30-day mortality was 24%
      (91/377), and the mortality of nosocomial bacteremia was significantly higher
      than that of community-acquired bacteremia (32% vs. 16%, p<0.001). Of all
      community-acquired and nosocomial isolates, 4% and 33%, respectively, were
      extended-spectrum cephalosporin (ESC)-resistant, and 4% and 21%, respectively,
      were ciprofloxacin (CIP)-resistant. In nosocomial infections, prior uses of ESC
      and CIP were found to be independent risk factors for ESC and CIP resistance,
      respectively. Significant differences were identified between community-acquired
      and nosocomial K. pneumoniae bacteremia, and the mortality of nosocomial
      infections was more than twice than that of community-acquired infections.
      Antimicrobial resistance was a widespread nosocomial problem and also identified
      in community-acquired infections.

PMID- 17043413
TI  - Seroprevalence of Coxiella burnetii infection in dairy cattle and non-symptomatic
      people for routine health screening in Korea.
AB  - We report results on the seroprevalence of antibodies to Coxiella burnetii in
      cattle and healthy people in Korea. Upon agreement with dairy owners, serum
      samples from 414 dairy cattle were collected between March and June 2001 and
      samples from 205 people for health screening were collected between April and
      December 2002. The sera were analyzed for the presence of anti-C. burnetii phase
      II antibodies using an indirect microimmunofluorescence test; strong fluorescence
      at a 1:32 dilution was regarded as positive. The overall seroprevalence of C.
      burnetii in cattle in Korea was 25.6%, with regional variation from 8.9 to 59.3%.
      Of the positive serum samples, 75.5% had antibody titers >or=1:256. By contrast,
      only 1.5% of people in a rural area were seropositive, and most of the positive
      samples had low antibody titers. In conclusion, this study showed that relatively
      high seropositivity of C. burnetii in dairy cattle, accordingly, the studies on
      the high-risk groups are needed to evaluate the seroprevalence for this organism
      in Korea.

PMID- 17043414
TI  - Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of
      methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.
AB  - Emergence and spread of low-level mupirocin resistance in staphylococci have been
      increasingly reported in recent years. The aim of this study was to characterize
      missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS)
      among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)
      with low-level mupirocin resistance. A total of 20 isolates of MRSA with low
      level mupirocin resistance (minimal inhibitory concentration, 16-64 microg/mL)
      were collected from 79 patients in intensive care units for six months. The
      isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might
      affect the binding of mupirocin to the three-dimensional structure of the S.
      aureus IleS enzyme. All isolates with low-level mupirocin resistance contained
      the known V588F mutation affecting the Rossman fold, and some of them
      additionally had previously unidentified mutations such as P187F, K226T, F227L,
      Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in
      stabilizing the conformation of the catalytic loop containing the KMSKS motif. In
      conclusion, this study confirms that molecular heterogeneity in ileS gene is
      common among clinical MRSA isolates with low-level mupirocin resistance, and
      further study on clinical mutants is needed to understand the structural basis of
      low-level mupirocin resistance.

PMID- 17043415
TI  - Clinical overview of extrapulmonary small cell carcinoma.
AB  - The objective of this study was to review the natural history of extrapulmonary
      small cell carcinoma (EPSCC) with specific emphasis on clinical features,
      response to treatment and survival. The records of all patients (n=34) with EPSCC
      treated at Yeungnam University Medical Center and Catholic University of Daegu
      Medical Center between 1998 and 2005 were retrieved and reviewed. The primary
      sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas
      and stomach in 5 patients each (14.7%); other sites included were the cervix,
      abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal
      cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had
      limited disease. The median survival of all patients was 14 months. Independent
      prognostic factors included stage and primary tumor location. The prognosis for
      the patients with extensive disease and in the gastrointestinal group was
      unfavorable. EPSCC is a non homogeneous disease entity. As a result of its
      frequent recurrence, multimodal therapy has a better outcome even in cases of
      limited disease. Combination chemotherapy plays a central role for treatment of
      extensive disease in EPSCC. Further multicenter studies are now needed to
      determine more details regarding disease sub-class and optimal treatment
      modality.

PMID- 17043416
TI  - Human metapneumovirus infection in hospitalized children with acute respiratory
      disease in Korea.
AB  - Human metapneumovirus (hMPV) is a recently isolated virus, mostly associated with
      acute lower respiratory infection in children, of which symptoms are similar to
      those of respiratory syncytial virus (RSV) infection. The aim of our study was to
      determine the frequency of hMPV in hospitalized children with acute respiratory
      tract disease in Korea. Nasal aspirates from hospitalized children with
      respiratory infections under 15 yr old between December 2003 and February 2005
      were included in the study. Each sample was analyzed for RSV, adenovirus,
      influenza virus A and B, and parainfluenza virus by indirect fluorescent assay
      (IFA). F-gene sequences were used for PCR for the detection and sequencing of
      hMPV. In total 381 samples, negative samples in which any viral pathogen could
      not be identified by IFA were 231 cases. hMPV was detected using reverse
      transcriptase-PCR (RT-PCR) in 28 of 231 (12.1%) children who were not infected
      with another respiratory viruses. The hMPV-infected children were diagnosed as
      having pneumonia, bronchiolitis, bronchial asthma exacerbation, croup, and upper
      respiratory tract infection. Most of the RT-PCR positive samples for hMPV were
      collected in winter season. These results suggest that hMPV may be a responsible
      pathogen causing acute respiratory tract infection in Korean children.

PMID- 17043417
TI  - The stages of change in smoking cessation in a representative sample of Korean
      adult smokers.
AB  - This study reports the stages of change in smoking cessation in a representative
      sample of Korean adult smokers. The study subjects, all adult smokers (n=2,422),
      were recruited from the second Korea National Health and Nutrition Examination
      Survey conducted in 2001. The stages of change were categorized using demographic
      (age and sex), socioeconomic (education, residence, and household income), and
      smoking characteristics (age at smoking onset, duration of smoking, and number of
      cigarettes smoked per day). Age-stratified analyses of the association of
      socioeconomic and smoking characteristics with the stages of change in male and
      female smokers were also conducted. According to the stages of change, the study
      population consisted of 37.6% (95% CI, 35.7-39.5) pre-contemplation, 56.0% (54.0
      58.0) contemplation, and 6.4% (5.4-7.4) preparation. The associations between the
      characteristics of the smokers and the stages of change were all statistically
      significant. The age-stratified analyses showed that all the socioeconomic and
      smoking characteristics were significantly associated with the stages in males,
      while education and residence had significant associations in females. This study
      revealed that a relatively small number of Korean smokers were prepared to quit
      and the stage distribution might be influenced by demographic, socioeconomic, and
      smoking characteristics.

PMID- 17043418
TI  - Mid-term follow up of patients using the St. Jude Medical Aortic Connector System
      for proximal vein graft in CABG.
AB  - The aortic connector system may reduce stroke during proximal venous anastomosis.
      However, the overall anastomotic patency rate has been generally reported to be
      low. From October 2002 to March 2004, 68 patients who received proximal
      anastomosis using the St. Jude Aortic Connector System were included in the
      study. There were 47 men and 21 women and their mean age was 65.68+/-6.68 yr old
      (52 to 85 yr). Grafts were evaluated by coronary angiography or multi-slice 16
      channel 3-D CT at 6 days and at 6 months postoperatively. In the immediate
      postoperative period, no stenosis was observed by either angiography (n=22) or 3D
      CT (n=46). At 6-month postoperatively, we performed either angiography (n=7) or 3
      D CT (n=52). Of these patients, 5 patients showed graft stenosis in the
      midportion, and 3 in the ostium. There were no stroke. Simple, and effective
      proximal anastomosis with good protection from cerebrovascular accident was
      achieved especially when calcification or atheromatous plaque was observed at the
      ascending aorta in the operation room. However, our mid term patency results
      raise concerns related to venous graft stenosis in the midportion. Therefore,
      longer follow up is recommended.

PMID- 17043419
TI  - The effect of milrinone on the right ventricular function in patients with
      reduced right ventricular function undergoing off-pump coronary artery bypass
      graft surgery.
AB  - This investigation evaluated the effect of continuous milrinone infusion on right
      ventricular (RV) function during off-pump coronary artery bypass graft (OPCAB)
      surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB,
      with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction,
      were randomly allocated to either milrinone (0.5 microg/kg/min) or control
      (saline) group. Hemodynamic variables and RV volumetric data measured by
      thermodilution method were collected as follows: after anesthesia induction (T1);
      10 min after heart displacement for obtuse marginal artery anastomosis (T2);
      after pericardial closure (T3). Cardiac index and heart rate increased and
      systemic vascular resistance significantly decreased in milrinone group at T2.
      Initially lower RVEF of milrinone group was eventually comparable to control
      group after milrinone infusion. RVEF did not significantly change at T2 and T3 in
      both groups. RV end-diastolic volume in milrinone group consistently decreased
      from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus
      demonstrated potentially beneficial effect on cardiac output and RV afterload in
      patients with reduced RV function during OPCAB. However, aggressive augmentation
      of intravascular volume seems to be necessary to maximize the effect of the
      milrinone in these patients.

PMID- 17043420
TI  - Transcatheter closure of fenestration with detachable coils after the Fontan
      operation.
AB  - We report our experience in 13 patients who underwent transcatheter closure of
      Fontan fenestration with the Cook detachable coils. These patients underwent the
      extracardiac type Fontan operation with a short conduit fenestration (n=7) or
      lateral tunnel type with a punch-hole fenestration (n=6). Fenestration closure
      was done at the mean age of 5.1+/-2.4 yr, average of 32 months after the Fontan
      operation. We used one to three coils depending on the fenestration type, size,
      and residual shunt. Aortic oxygen saturations increased by an average of 5.4 (2
      9)% and mean pressures in the Fontan circuit increased by an average of 2.1 (0-6)
      mmHg. During follow-up (median of 23 months), five patients (4 in extracardiac, 1
      in lateral tunnel) had complete occlusion of the fenestration on
      echocardiography. There was no immediate or late complication. Transcatheter
      closure of fenestration in Fontan operation using the Cook detachable coil is a
      safe and feasible technique. However, the coil was ineffective for closure of a
      punch-hole fenestration in the lateral tunnel type operation. In the conduit type
      fenestration, some modification of fenestration method instead of a short conduit
      for coil closure or use of new device is necessary to increase complete closure
      rate.

PMID- 17043421
TI  - Sentinel lymph node radiolocalization with 99mTc filtered tin colloid in
      clinically node-negative squamous cell carcinomas of the oral cavity.
AB  - The objective of this study was to evaluate the feasibility of sentinel lymph
      node biopsy by using a radiotracer lymphatic mapping technique in patients with
      squamous cell carcinoma of the oral cavity, and the diagnostic value of this
      technique. We studied twenty patients with previously untreated squamous cell
      carcinomas of the oral cavity and N0 necks. After the peritumoral injection of
      99mTc filtered tin colloid preoperatively, lymphoscintigraphy and intraoperative
      mapping using a gamma detector were performed to localize sentinel nodes. An open
      biopsy of the sentinel node was followed by complete neck dissection. We
      identified the sentinel nodes in 19 of 20 patients (95.0%) by lymphoscintigraphy
      and in all (100%) by intraoperative gamma detector. In all cases, the status of
      the sentinel node accurately predicted the pathologic status of the neck with the
      false negative rate being 0%. The negative predictive value for the absence of
      cervical metastases was 100%. In conclusion, our radiolocalization technique of
      sentinel nodes using 99mTc filtered tin colloid in N0 squamous cell carcinomas of
      the oral cavity is technically feasible and appears to accurately predict the
      presence of the occult metastatic disease.

PMID- 17043422
TI  - Expression of cyclooxygenase-2, p53 and Ki-67 in gastric cancer.
AB  - It has been reported that p53 mutation may contribute to upregulate
      cyclooxygenase (COX)-2 expression that is observed in malignant tissues. These
      molecules are involved in carcinogenesis by affecting tumor cell proliferation.
      The aim of this study was to examine the relationship between COX-2 or p53
      expression and clinico-pathological characteristics including tumor cell
      proliferation in gastric cancer. COX-2 and p53 expressions were investigated with
      immunostaining, in tissue specimens obtained from 119 patients who underwent
      surgery for gastric cancer. The Ki-67 labeling index (LI) was counted by Ki-67
      immunostaining. COX-2 and p53 expressions correlated significantly with depth of
      tumor invasion. However, there was no association between COX-2 or p53 expression
      and survival. p53 expression did not correlate with COX-2 expression. There was
      no significant difference in various clinicopathological variables between Ki-67
      LI subgroups. The mean Ki-67 LI value of COX-2 positive tumors was significantly
      higher than that of negative tumors. The mean Ki-67 LI value of p53 positive
      tumors was not significantly higher than that of negative tumors. The mean Ki-67
      LI value of both COX-2 and p53 positive tumors was significantly higher than that
      of both negative tumors. These results imply that COX-2 expression is associated
      with tumor cell proliferation of gastric cancer.

PMID- 17043423
TI  - Overexpression of CIITA in T cells aggravates Th2-mediated colitis in mice.
AB  - The MHC class II transactivator (CIITA) is the master transcriptional regulator
      of genes involved in MHC class II restricted antigen presentation. Previously we
      suggested another role of CIITA in Th1/Th2 balance by demonstrating that forced
      expression of CIITA in murine T cells repressed Th1 immunity both in vitro and in
      vivo. However, the results were contradictory to the report that CIITA functioned
      to suppress the production of Th2 cytokine by CD4+ T cells in CIITA deficient
      mice. In this study, we investigated the influence of constitutive expression of
      CIITA in T cells on Th2 immune response in vivo using murine experimental colitis
      model. In the dextran sodium sulfate-induced acute colitis, a disease involving
      innate immunity, CIITA transgenic mice and wild type control mice showed similar
      progression of the disease. However, the development of oxazolone-induced
      colitis, a colitis mediated by predominantly Th2 immune response, was aggravated
      in CIITA-transgenic mice. And, CD4+ T cells from the mesenteric lymph node of
      CIITA-transgenic mice treated with oxazolone exhibited a high level of IL-4
      secretion. Together, these data demonstrate that constitutive expression of CIITA
      in T cells skews immune response to Th2, resulting in aggravation of Th2-mediated
      colitis in vivo.

PMID- 17043424
TI  - Antibiotic prophylaxis using third generation cephalosporins can reduce the risk
      of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a
      prospective randomized study.
AB  - Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic
      prophylaxis can prevent rebleeding in patients with acute gastroesophageal
      variceal bleeding (GEVB). The aim of the study was to compare prophylactic third
      generation cephalosporins with on-demand antibiotics for the prevention of
      gastroesophageal variceal rebleeding. In a prospective trial, patients with the
      first acute GEVB were randomly assigned to receive prophylactic antibiotics
      (intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or
      to receive the same antibiotics only when infection became evident (on-demand
      group). Sixty-two patients in the prophylactic group and 58 patients in the on
      demand group were included for analysis. Antibiotic prophylaxis decreased
      infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the
      prophylactic group was significantly lower than that in the on-demand group
      (33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to
      early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate
      analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval
      (CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95%
      CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding.
      In conclusion, antibiotic prophylaxis using third generation cephalosporins can
      prevent bacterial infection and early rebleeding in patients with the first acute
      GEVB.

PMID- 17043425
TI  - Expression of the RERG gene is gender-dependent in hepatocellular carcinoma and
      regulated by histone deacetyltransferases.
AB  - Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel
      gene that was first reported in breast cancer. However, the functions of RERG are
      largely unknown in other tumor types. In this study, RERG expression was analyzed
      in hepatocellular carcinomas of human patients using reverse transcriptase PCR
      analysis. In addition, the possible regulation of RERG expression by histone
      deacetyltransferases (HDACs) was studied in several cell lines. Interestingly,
      the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of
      male patients (57.9%) but decreased in HCC of females (87.5%) comparison with
      paired peri-tumoral tissues. Moreover, RERG gene expression was increased in
      murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse
      normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A.
      Our results suggest that RERG may function in a gender-dependent manner in
      hepatic tumorigenesis and that the expression of this gene may be regulated by an
      HDAC-related signaling pathway.

PMID- 17043426
TI  - Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno
      occlusive disease of the liver after allogeneic hematopoietic stem cell
      transplantation in Korean children.
AB  - Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive
      disease (VOD) development are rare in children that have undergone allogeneic
      hematopoietic stem cell transplantation (HSCT). This study examined risk factors
      for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1
      (lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic
      HSCT. Eighty five children underwent HSCT between June 1997 and September 2004.
      Patients were diagnosed and classified as having mild, moderate or severe VOD
      according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed
      VOD. VOD occurred more frequently in patients receiving busulfan-based
      conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other
      (0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non
      malignant disease compared to those with malignant disease (p<0.05). Survival at
      day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%,
      p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to
      develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis
      developed severe VOD. Given severe VOD is associated with a high mortality rate,
      this study indicates that prophylactic heparin or lipo-PGE1 may decrease
      mortality in children undergoing HSCT.

PMID- 17043427
TI  - Increased expression of heat shock protein 72 protects renal proximal tubular
      cells from gentamicin-induced injury.
AB  - The nephrotoxicity of gentamicin (GM) has been widely recognized. Heat shock
      protein 72 (HSP72) has been reported to be a cytoprotectant. However, its
      cytoprotective effect against GM induced kidney injury has not yet been studied.
      In this study, we investigated the cytoprotective effect of HSP72 on GM-induced
      nephrotoxicity in vitro. Human Kidney tubular cell line, HK-2 cells were divided
      into four groups: control group, GM group (cells incubated with GM only), heat
      shock (HS) group (cells incubated at 43 degrees C for 30 min), and GM plus HS
      group, respectively. Lactate dehydrogenase (LDH) release increased time
      dependently from 24 hr to 96 hr compared to the data of cells treated with GM
      only. Results of NAG activities, superoxide dismutase (SOD) activities and
      malondialdehyde (MDA) content were similar to that of the LDH release. The amount
      of HSP72 positive cells increased significantly at 72 hr after cells were treated
      with GM only. Both HSP72 protein and gene expression increased significantly at
      72 hr when cells were treated with GM. On the other hand, HS induced HSP72
      expression markedly. Pretreatment of HS inhibited HK-2 cells from GM-induced
      injury. It could reduce LDH release and NAG activity. HS also increased SOD
      activity, and decreased MDA content when cells were damaged by GM. These findings
      suggested that HS may protect kidney cells from GM-induced injury. Pre-induction
      of HSP72 may provide therapeutic strategies for nephrotoxicity induced by GM.

PMID- 17043428
TI  - Diagnostic relevance of pressure-controlled discography.
AB  - Discogenic pain is a leading cause of chronic low back pain. The authors
      investigated the efficacy of pressure-controlled discography to determine its
      role in clinical decision-making for the management of patients with discogenic
      pain. Pressure-controlled discography was performed in 21 patients (51 discs)
      with pain-provocation, followed by post-discography computerized tomography
      scans. Pain response was classified as positive response and negative response,
      and measured with visual analog scale scores. Discographic findings were graded
      by the modified Dallas discogram scale. Elastance, pain provocation on
      intradiscal pressure, pressure and volume of initial pain response, and pain
      response intensity were statistically analyzed. Elastance showed significant
      differences between Grade 0 and Grade 4 and 5. Decreased elastance with positive
      pain response group was a good indicator to imply that disc degeneration
      presumably is a pain generator. Results of pain response were well correlated
      with intradiscal pressure but not with the amount of injected volume. Among 31
      discs of Grade 4 and 5, 74% showed negative pain response and 26% showed positive
      response. It was concluded that pressure-controlled discography was useful to
      diagnose discogenic pain and excellent guide in decision-making for spinal
      operations.

PMID- 17043429
TI  - The changes of skin temperature on hands and feet during and after T3
      sympathicotomy for palmar hyperhidrosis.
AB  - Unilateral thoracic sympathectomy in patients with palmar hyperhidrosis causes a
      skin temperature drop in the contralateral hand. A cross-inhibitory effect by the
      post-ganglionic neurons innervating hands is postulated as a mechanism of
      contralateral vasoconstriction. The purpose of our study was to evaluate whether
      this cross-inhibitory effect also occurs in the feet. Twenty patients scheduled
      for thoracoscopic sympathicotomy due to palmar hyperhidosis were studied. Right
      T3 sympathicotomy was performed first, followed by left T3 sympathicotomy. The
      thenar skin temperatures of both hands and feet were continuously monitored using
      a thermometer and recorded before induction of anesthesia, during the operation,
      4 hr after and 1 week later. Following right T3 sympathicotomy, the skin
      temperature of the ipsilateral hand gradually increased, however the skin
      temperature of the contralateral hand gradually decreased. Immediately after
      bilateral sympathicotomy, the skin temperature differences between hands and feet
      increased, but these differences decreased 1 week later. Our results show that
      cross-inhibitory control may exist in feet as well as in the contralateral hand.
      Thus, the release of cross-inhibitory control following T3 sympathicotomy results
      in vasoconstriction and decrease of skin temperature on the contralateral hand
      and feet. One week later, however, the temperature balance on hands and feet
      recovers.

PMID- 17043430
TI  - Endothelial nitric oxide gene T-786C polymorphism and subarachnoid hemorrhage in
      Korean population.
AB  - We aimed to elucidate whether the eNOS T-786C mutant allele is implicated in
      subarachnoid hemorrhage (SAH) susceptibility or vasospasm after SAH, and whether
      the mutant allele is differentially expressed in those with small and large
      ruptured aneurysms in Korean population. 136 consecutive patients diagnosed with
      aneurismal SAH and 113 controls were recruited. Polymerase chain reaction and
      direct sequencing of both strands were performed to determine genotypes with
      respect to the eNOS T-786C mutation. No significant difference was found between
      cases and controls with respect to the distributions of the two eNOS T-786C
      single nucleotide polymorphism (SNP) genotypes. No significant differences in the
      distributions of the eNOS T-786C SNP genotypes were found with regard to the
      sizes of ruptured aneurysms or the occurrence of vasospasm after SAH. Multiple
      logistic regression analysis after controlling for age and sex showed the eNOS T
      786C SNP T/C geno-type was independently associated with an unfavorable outcome
      (GOS grade 3-5) of SAH (Exp (beta)=4.27, 95% CI 1.131-16.108, p=0.032). In
      conclusion, the eNOS T-786C mutation was not found to be associated with either a
      susceptibility to SAH or vasospasm after SAH, or with aneurysm size in Korean
      population. The eNOS T-786C SNP T/C genotype could be used as a prognostic marker
      in individuals with SAH.

PMID- 17043431
TI  - Abdominal ultrasonography findings in patients with spinal cord injury in Korea.
AB  - This is a retrospective study of 500 patients with spinal cord injury who
      underwent abdominal ultrasonography as a routine screening test from 2000 to
      2003. We analyzed the results according to the different abdominal organ systems.
      Among the 500 cases, 226 (45.2%) showed abnormal findings. 98 cases of abnormal
      findings in the liver included 75 of fatty liver and 13 of mass. The 88 cases of
      abnormal findings in the bladder included 56 of bladder wall thickening, 14 of
      cystitis and 10 of urinary stone. The 35 cases of abnormal findings in the kidney
      included 19 of renal cyst and 6 of pelvic dilatation. The 35 cases with
      gallbladder abnormalities included 19 with gallstones and 11 with biliary sludge.
      Excluding the cases with bladder wall thickening, there were still 170 cases with
      abnormal ultrasonographic findings. Abdominal sonography seems to be a useful
      tool in detecting hidden intraabdominal pathologies in patients with spinal cord
      injury.

PMID- 17043432
TI  - A case of imported Plasmodium ovale malaria.
AB  - There have been reports in Korea of imported malaria cases of four Plasmodium
      species, but there has been no report of imported Plasmodium ovale malaria
      confirmed by molecular biological methods. We report an imported case of that was
      confirmed by Wright-Giemsa-stained peripheral blood smear and nested polymerase
      chain reaction targeting the small subunit ribosomal RNA gene. The amplified DNA
      was sequenced and compared with other registered P. ovale isolates. The isolate
      in this study was a member of the classic type group. The patient was a 44-yr-old
      male who had worked as a woodcutter in Cote d'Ivoire in tropical West Africa. He
      was treated with hydroxychloroquine and primaquine and discharged following
      improvement. In conclusion, P. ovale should be considered as an etiology in the
      imported malaria in Korea, because the number of travelers to P. ovale endemic
      regions has recently increased.

PMID- 17043433
TI  - A case of leukemic pleural infiltration in atypical chronic myeloid leukemia.
AB  - Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and
      rarely reported in the literature. When the pleural effusion is caused by
      leukemic pleural infiltration, the differential white blood cell count of the
      effusion is identical to that of the peripheral blood, and the fluid cytology
      reveals leukemic blasts. We report here a case of bilateral pleural involvement
      of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with
      abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone
      marrow examination, chromosome analysis and polymerase chain reaction he was
      diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement
      negative CML. Following 3 months of treatment with gemcitabine for pancreatic
      cancer, he developed bilateral pleural effusions. All stages of granulocytes and
      a few blasts were present in both the pleural fluid and a peripheral blood smear.
      After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.

PMID- 17043434
TI  - Primary cardiac sarcoma in pregnancy: a case report.
AB  - Primary cardiac sarcoma is a rare disease in adults. It is also associated with
      poor prognoses, due to diagnostic delay, therapeutic difficulty, and high
      metastatic potential. The coincidence of pregnancy and a primary cardiac intimal
      sarcoma is extremely rare. We report a pregnant woman at 27(+5) weeks gestation
      who was admitted to the hospital with acute-onset dyspnea. A mass was found on
      the left atrium by transthoracic echocardiography. Subsequently, the intracardiac
      mass was removed, and mitral valve replacement and modified DeVega tricuspid
      annuloplasty were performed. The patient was diagnosed with a undifferentiated
      sarcoma, and gave birth to a 1,230 g living baby boy by Caesarean section from
      preterm contraction at 29(+5) weeks gestation. The patient then received systemic
      chemotherapy. However, 10 months after the initial clinical onset, the patient
      suddenly died. Surgery is the standard treatment for cardiac tumors, and their
      removal should always be attempted, even in pregnant women. Although the overall
      survival rates of the patients are rather poor, palliative cardiac surgery allows
      the prolonging of pregnancy, until an acceptable fetal viability level is
      reached.

PMID- 17043435
TI  - Vibrio cholerae non-O1,non-O139 isolated from pleural effusion following total
      gastrectomy.
AB  - We isolated non-O1, non-O139 Vibrio cholerae from pleural effusion in a patient
      with recurred advanced gastric cancer after total gastrectomy. We also recovered
      the organism from the patient's stool culture. The patient did not experience
      gastrointestinal symptoms such as diarrhea except heartburn and epigastric
      discomfort from stomach cancer before admission. The suspected route of infection
      is directly from the gastrointestinal tract through the previous surgical wounds.
      After antibiotic treatment, no more V. cholerae was isolated and the patient was
      well discharged from the hospital. This is the first report of V. cholerae
      infection associated with pleural effusion in a long-term latent carrier of the
      organism.

PMID- 17043436
TI  - Etanercept-induced systemic lupus erythematosus in a patient with rheumatoid
      arthritis.
AB  - Tumor necrosis factor (TNF) is known to play a critical role in the pathogenesis
      of rheumatoid arthritis (RA). Etanercept is a recombinant soluble fusion protein
      of TNF alpha type II receptor and IgG, which acts as a specific TNF-alpha
      antagonist. Anti-TNF-alpha therapy has been an important advance in the treatment
      of RA. However, induction of autoantibodies in some proportion of patients
      treated with TNF alpha inhibitors raised concerns for development of systemic
      autoimmune diseases such as systemic lupus erythematosus (SLE). Although new
      autoantibody formation is common with anti-TNF alpha therapy, there are only rare
      reports of overt SLE, most of which manifested without major organ involvement
      and resolved shortly after discontinuation of the therapy. We describe a 55-yr
      old Korean woman who developed overt life threatening SLE complicated by
      pneumonia and tuberculosis following etanercept treatment for RA. This case is to
      our knowledge, the first report of etanercept-induced SLE in Korea.

PMID- 17043437
TI  - Cavernous angioma in the falx cerebri: a case report.
AB  - Intracranial cavernous angiomas are benign vascular malformations and can be
      divided into intra-axial and extra-axial lesions. Extra-axial cavernous angiomas
      are relatively rare and usually arise in relation to the dura mater and mimick
      meningiomas. We report a case of cavernous angioma that occurred in the falx
      cerebri of a 22-yr-old female patient with the special focus on neuroradiologic
      findings. This is the fourth case of cavernous angioma in the falx cerebri
      reported in the literature to our knowledge.

PMID- 17043438
TI  - A case of infantile Alexander disease accompanied by infantile spasms diagnosed
      by DNA analysis.
AB  - Alexander disease (AD) is a rare leukodystrophy of the central nervous system of
      unknown etiology. AD is characterized by progressive failure of central
      myelination and the accumulation of Rosenthal fibers in astrocytes, and is
      inevitably lethal in nature. Symptomatically, AD is associated with
      leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in
      infants, and usually leads to death within the first decade. Its characteristic
      magnetic resonance imaging (MRI) findings have been described as demyelination
      predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene,
      coding for glial fibrillary acidic protein (GFAP), a principal astrocytic
      intermediate filament protein, have been shown to lead to AD. The disease can now
      be detected by genetic diagnosis. We report the Korean case of an 8-month-old
      male patient with AD. He was clinically characterized due to the presence of
      psychomotor retardation, megalencephaly, spasticity, and recurrent seizures
      including infantile spasms which is a remarkable presentation. Demyelination in
      the frontal lobe and in a portion of the temporal lobe was demonstrated by brain
      MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L
      mutation in the GFAP gene, involving the replacement of guanine with thymine.

PMID- 17043439
TI  - Intracranial dural arteriovenous fistula draining into spinal perimedullary
      veins: a rare cause of myelopathy.
AB  - We report a rare case of progressive myelopathy caused by intracranial dural
      arteriovenous fistula with venous drainage into the spinal perimedullary veins. A
      45-yr-old man developed urinary and fecal incontinence and muscle weakness in the
      lower limbs. Magnetic resonance imaging revealed brainstem edema and dilated
      veins of the brainstem and spinal cord. Cerebral angiography showed a dural
      arteriovenous fistula fed by the neuromeningeal branch of the left ascending
      pharyngeal artery. Occlusion of the fistula could be achieved by embolization
      after a diagnostic and subsequent therapeutic delay. There was no improvement in
      clinical condition. For the neurologic outcome of these patients it is important
      that fistula must be treated before ischemic and gliotic changes become
      irreversible.

PMID- 17043440
TI  - COXIBs: interpreting the swell of phase IV data.

PMID- 17043441
TI  - Association of primary biliary cirrhosis and rheumatoid arthritis.
AB  - Primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA) are chronic medical
      conditions in which, although the etiology is uncertain, autoimmune features
      predominate. These two conditions are, in fact, multisystemic diseases, with a
      multitude of manifestations that are not limited to their target end organ. It
      has been well established that patients with PBC may have musculoskeletal
      complaints and patients with RA may have evidence of hepatic dysfunction. Both of
      these conditions are fairly rare, with RA being found in approximately 1% of the
      population and PBC being found in approximately 20/100,000 women and 2/100,000
      men.The likelihood of these uncommon conditions occurring in the same patient is
      very rare and unusual. We have identified a unique group of 25 patients who have
      met disease-defining criteria for both RA and PBC. Awareness of this combination
      should prompt rheumatologists to assess for PBC with antimitochondrial antibody
      testing in patients with abnormal liver tests and also to raise awareness that
      abnormal liver tests in RA patients are not always due to drugs.

PMID- 17043442
TI  - Patient perception of the burden of weight gain and blood pressure increase among
      RA patients using celecoxib, rofecoxib, and non-specific NSAIDs.
AB  - Nonsteroidal anti-inflammatory medications (NSAIDs) may be accompanied by
      clinically important renal side effects. We compared the rate of reported side
      effects from celecoxib, rofecoxib, and nonspecific (NS) NSAIDs and their burden
      in RA patients. Patients on rofecoxib were more likely to report a problem with
      weight gain (P < 0.05) and an increase in blood pressure (P < 0.001). In
      addition, rofecoxib users were 28% more likely to be in a more severe category
      for being bothered by unintentional weight gain (OR = 1.28, P < 0.05) and 53%
      more likely to state that they were in a more severe category for blood pressure
      increase (OR = 1.53, P < 0.000), compared with patients receiving celecoxib.
      Weight gain and blood pressure were also increased by coexisting cardiovascular
      disease. Clinicians should be aware that patient-reported weight gain and
      increases in blood pressure can occur with all NSAIDs, and may be particularly
      increased with rofecoxib. Existing cardiovascular disease is also an independent
      predictor of weight gain and increased blood pressure.

PMID- 17043443
TI  - A patient with wegener granulomatosis and intraventricular hemorrhage.
AB  - We report a case of intraventricular hemorrhage (IVH) in a 27-year-old man with
      Wegener granulomatosis (WG), successfully treated with corticosteroids and
      cyclophosphamide. Neurologic manifestations occur in 22%-54% of patients with WG,
      with cerebral vasculitis in less than 5%. Only 2 cases of IVH associated with WG
      have been reported at autopsy. This is the first reported case of in situ IVH
      associated with WG in a patient who survived. In patients with WG who present
      with neurologic manifestations, cerebral vasculitis with secondary intracranial
      hemorrhage should be considered, as these patients are often resistant to
      immunosuppressive therapies and may present with normal angiograms.

PMID- 17043444
TI  - Thiemann disease.
AB  - Thiemann disease is a rare genetic disorder that is considered to be a form of
      avascular necrosis of the proximal interphalangeal joints of the fingers and
      toes. The clinical symptoms usually appear in adolescence or puberty and may be
      confused with juvenile rheumatoid arthritis. The characteristic symmetrical,
      firm, relatively painless deformity and x-ray findings of the epiphysical
      irregularities should suggest the diagnosis. As rheumatologists become more
      familiar with the disease, it may be more frequently and promptly diagnosed.

PMID- 17043445
TI  - Cellulitis and septic arthritis caused by Campylobacter fetus and Campylobacter
      jejuni: report of 2 cases and review of the literature.
AB  - Bacteremia caused by gram-negative bacteria occasionally causes soft tissue
      infections, including cellulitis and septic arthritis. We describe 1 patient each
      with Campylobacter fetus cellulitis and septic arthritis and review the world
      literature with regard to C. fetus and C. jejuni infections at these sites.
      Altogether, 14 patients with cellulitis (12 due to C. fetus and 2 due to C.
      jejuni) and 20 patients with septic arthritis (15 due to C. fetus and 4 caused by
      C. jejuni) have been described. Most infections, particularly those causing
      cellulitis, are found in elderly men with underlying systemic disease. Most
      patients are febrile but less than half manifest a leukocytosis. There were only
      3 deaths in this series of 33 patients. The newer macrolides, including
      azithromycin and clarithromycin, are considered the drugs of choice, particularly
      with C. jejuni, while soft tissue infections caused by C. fetus respond nicely to
      many beta-lactams, particularly to cephalosporins and carbapenems, as well as to
      macrolides and quinolones.

PMID- 17043446
TI  - Soft tissue metastases presenting as greater trochanteric pain syndrome.
AB  - Greater trochanteric pain syndrome includes a complex differential diagnosis. We
      report the case of a 71-year-old woman who consulted us because of pain in the
      lateral aspect of the hip. A diagnosis of greater trochanter bursitis was
      suggested, and she was treated with local injections of a mixture of
      corticosteroids plus anesthetic, but the condition did not improve. A pelvic MRI
      showed a high intensity signal in the gluteus medius and minimus and a subsequent
      biopsy revealed a metastasis of an adenocarcinoma of unknown origin. Although
      pain on the lateral aspect of the hip is often attributed to trochanteric
      bursitis, other diagnoses, including this rare finding of malignant disease,
      should be considered in the differential diagnosis of the greater trochanteric
      pain syndrome.

PMID- 17043447
TI  - Oncogenic hypophosphatemic osteomalacia associated with a nasal
      hemangiopericytoma.
AB  - We report a patient with a nasal hemangiopericytoma associated with an oncogenic
      hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products
      that decrease renal tubular phosphate resorption, leading to the osteomalacia.
      This patient presented with classic bone manifestations of osteomalacia and a
      nasal tumor. Laboratory studies performed before the first resection of the tumor
      included normal serum calcium, hypophosphatemia due to decreased tubular
      reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D
      level. Serum parathormone level was normal. Anterior iliac crest bone biopsy
      showed characteristic signs of osteomalacia that included increased osteoid and
      delayed mineralization. A partial resection of the nasal tumor was performed.
      After the first surgery the patient showed detectable serum level of 1,25
      dihydroxy vitamin D, and transient normalization of the tubular reabsorption of
      phosphate. The patient was also treated with phosphate supplements and vitamin D
      with transient control of her clinical manifestations and improvement of the
      radiographic signs of osteomalacia. Three months after surgery, the serum level
      of 1,25 dihydroxy vitamin D level again became undetectable. After selective
      embolization of the tumor, followed by an apparent complete tumor resection and
      postoperative radiation therapy, her hypophosphatemia and decreased phosphate
      tubular reabsorption persisted. Therefore, biochemical changes associated with
      hemangiopericytoma induced OHO may persist even after apparent total tumor
      resection. Clinicians should be aware of the oncogenic basis for some
      osteomalacia, as seen in this patient.

PMID- 17043448
TI  - Tophaceous gout in a patient with thalassemia.
AB  - We report a 46-year-old Greek female with thalassemia intermedia, who presented
      to our hospital with end stage renal disease of unknown etiology and tophaceous
      gout. In addition, skeletal manifestations characteristic of thalassemia were
      noted with massive extramedullary hematopoiesis presenting as posterior
      mediastinal masses. We report the first case in English literature of crystal
      proven gout in thalassemia intermedia and provide a review of the literature that
      indicates the relative rarity of gout in this clinical setting, despite evidence
      of urate overproduction in one report. The long survival and renal insufficiency
      may have contributed to our patients' tophaceous gout.

PMID- 17043449
TI  - Anticipating rather than confirming drug toxicity through selective laboratory
      testing.

PMID- 17043450
TI  - Epidemiology of Wegener granulomatosis since the introduction of ANCA testing in
      Olmsted County, MN, 1990-1999.

PMID- 17043451
TI  - Color Doppler ultrasound of the hand: observations on clinical utility in
      rheumatoid arthritis.
AB  - The use of ultrasound with color Doppler in the evaluation of rheumatoid
      arthritis was followed in 25 patients with joint complaints. Small joint
      ultrasound of the metacarpophalangeal joints (MCPs) as well as the wrists was
      performed with supplementation by color Doppler. In addition, 6 patients were
      followed for at least 3 months after start of treatment of rheumatoid arthritis
      using the same technique. In patients with what appeared to be definite
      rheumatoid arthritis, ultrasound supported this diagnosis as evidenced by the
      finding of cortical defects, extensor tendon sheath thickening, and synovial
      proliferation. Increased activity by color Doppler ultrasonography was the most
      common finding. Significant decrease in color Doppler activity was noted in the 6
      patients who were followed up after 3 months of therapy with disease-modifying
      agents. Therefore, the use of ultrasound with color Doppler could aid in the
      diagnosis and follow up of patients with rheumatoid arthritis.

PMID- 17043452
TI  - Health-related quality of life and support group attendance for patients with
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with
      variable symptoms. Severity of disease has been associated with mental and
      physical health-related quality of life (HRQoL). The potential effects of support
      groups have not been examined. We examined the possible improvement in mental and
      physical HRQoL of women with SLE who attended support groups. Thirty-four women
      who attended support groups and 71 comparison women with SLE were recruited. Self
      administered surveys included the Medical Outcomes Study Short-Form 36 (SF-36)
      and a 3-level rating of disease activity.Mean SF-36 Mental Health Summary Scale
      scores (MCS) were significantly lower for women attending groups (31.5) compared
      with nonattending SLE women (39.8). MCS scores were lower for blacks compared
      with whites (33.7 vs. 39.2, P <0.05). Women with high and moderate disease
      activity had lower MCS scores compared with those with low activity (28.6 or 35.6
      vs. 42.7, P <0.05). In linear regression, 27% of the variation in MCS was
      explained by support group attendance, disease activity, race, and age.Overall,
      women with SLE reported lower MCS and physical health summary scales (PCS) scores
      than published population values, indicating markedly reduced quality of life.
      Any potential positive effects of support groups will need to be tested in a
      prospective random design to assess improvements in HRQoL.

PMID- 17043453
TI  - How to keep a wet preparation of synovial fluid.
AB  - Identification of crystals in the synovial fluid (SF) is mandatory for the
      diagnosis of a microcrystal deposition arthropathy. In some cases, this analysis
      can be troublesome, especially in medical centers where a qualified practitioner
      is not continually present. Therefore, we investigated a method for preservation
      of a wet preparation of SF for 24 hours at room temperature. The procedure
      consisted in storing the preparation in a closed Petri plate whose bottom was
      covered by a cellulose compress moistened with saline (0.9% sodium chloride)
      separated from the slide by 2 wooden or glass sticks. The joint aspirates of 20
      consecutive patients with various microcrystal arthropathies were read
      immediately after aspiration and reviewed after 24 hours on the slides stored
      according to the previously mentioned procedure. For 11 of the 20 cases, a second
      SF preparation was stored in normal conditions. The amounts of crystals were
      estimated semiquantitatively.Preparations stored in the Petri plates were clearly
      readable after 24 hours and crystals still identifiable on each slide. The
      amounts of crystals were still the same. After 24 hours, the preparations stored
      in normal conditions were dry, the shapes of the crystals were blurred, their
      amount was reduced, and birefringent artifacts were seen. In conclusion, when the
      amounts of SF are small and a skilled technician or a rheumatologist is not
      immediately available for reading the preparation, storing the wet preparation of
      SF in a moistened Petri plate can prove useful.

PMID- 17043454
TI  - Sarah's Knee: A Famous Actress With Chronic, Inflammatory Monoarthritis.
AB  - Sarah Bernhardt had a recurrent and later persistent inflammatory arthritis of
      her right knee for more than 25 years. She probably had pulmonary tuberculosis,
      starting a dozen years before the arthritis, and her chronic synovitis may have
      been tuberculous. Several months in a cast led to deterioration and later
      amputation of the leg, an outcome that might have been prevented by surgical
      arthrodesis. Despite the loss of her limb and progressive renal failure, she
      continued an active theatrical career until her death at age 78.

PMID- 17043455
TI  - Takayasu arteritis presenting with Fever of unknown origin: two case reports.
AB  - Two patients with Takayasu arteritis are reported who presented with fever of
      unknown origin. Takayasu arteritis was diagnosed at the prepulseless period after
      stenotic lesions of the aorta, and its branches were seen with imaging methods.
      In the first month of steroid treatment, hypertension developed in both patients
      that was related to fibrosis in stenotic lesions in renal arteries. Both patients
      were treated with percutaneous transfemoral renal angioplasty. Takayasu arteritis
      should be considered in the differential diagnosis of fever of unknown origin,
      especially in young women. Absence of the physical findings related to vasculitic
      lesions will not rule out the disease, which can be seen in the prepulseless
      period.

PMID- 17043456
TI  - Elastofibroma dorsi: an unusual case of a subscapular nodular mass.
AB  - Elastofibroma dorsi is a benign, slow-growing soft tissue tumor. Poorly
      symptomatic, it raises an important differential diagnosis with benign and
      malignant tumors of the subscapular region, and with a differential diagnosis
      with shoulder pain and snapping scapula. It is seen in elderly women and occurs
      more frequently in the subscapular region, although it has been reported in
      several locations. We report the case of a 58-year-old woman who presented with
      upper gastrointestinal bleeding. During the physical examination, a mass was
      found in the right subscapular region. Months later, the patient presented with
      pain on right arm motion and an increase in the size of the mass. Complete
      surgical excision was performed. The patient is free of symptoms with no
      recurrences of the tumor so far. Consider this benign tumor if a lipoma-like
      nodule or mass becomes symptomatic.

PMID- 17043457
TI  - Tubulointerstitial Nephritis With Uveitis (TINU): A Syndrome Rheumatologists
      Should Recognize: A Case Report and Review of the Literature.
AB  - Patients with uveitis such as the patient whose case is reported here are often
      referred to rheumatologists for investigation of possible underlying systemic
      diseases. This patient presented with decreased vision, photophobia, weight loss,
      and fevers and was found to have uveitis, elevated creatinine, and interstitial
      nephritis. This raised consideration of a variety of systemic diseases before she
      was determined to have the tubulointerstitial nephritis with uveitis (TINU)
      syndrome. The TINU syndrome, although known to some ophthalmologists and
      nephrologists, is still rather obscure. Uncommon but not rare with 133 cases in
      the literature, TINU syndrome should be one more diagnosis to be considered in
      patients with uveitis. The median age of onset is 15, but it ranges from 9 to 74.
      There is a 3:1 female preponderance. Response to corticosteroids, which are used
      in 80% of reported cases, is rapid. The prognosis for the renal disorder is
      excellent, although the uveitis often recurs or remains chronic.

PMID- 17043458
TI  - Successful therapy of rheumatoid arthritis with rituximab: renewed interest in
      the role of B cells in the pathogenesis of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is often considered a T cell-mediated disease, yet
      recent studies describe benefit with rituximab, a monoclonal antibody directed
      against the B cell antigen CD20. We report our experience using rituximab for 5
      patients with severe, disease-modifying antirheumatic drug (DMARD)-refractory RA.
      Five patients with seropositive, erosive RA received rituximab as 4 weekly doses
      of 375 mg/m. Four subjects experienced remission lasting 5 to 12 months after
      noting lack of efficacy with antitumor necrosis factor (TNF) therapy. All
      patients have relapsed, with signs and symptoms of RA returning a mean of 8
      months after therapy. Rituximab appears to be a safe and potentially helpful
      treatment of refractory RA and, until U.S. Food and Drug Administration approval,
      could be considered for compassionate use in people who have failed multiple
      DMARDs. Individuals who do not respond to anti-TNF therapy could experience
      arthritis that is perpetuated by B cell more than T cell function; these patients
      could be most likely to respond to rituximab. Further studies are needed to
      clarify the optimal dose and frequency of rituximab therapy, and its role in
      combination therapy for individuals with RA.

PMID- 17043459
TI  - Evidence-based soft tissue rheumatology: epicondylitis and hand stenosing
      tendinopathy.
AB  - Lateral and medial epicondylitis represent overuse tendinopathies of wrist
      extensor and wrist flexor muscles, respectively. In lateral epicondylitis, a
      short-term therapeutic efficacy of glucocorticoid injection and limited evidence
      on the efficacy of acupuncture has been shown. De Quervain tendinopathy is caused
      by tendinous impingement by a thickened retinaculum. There is limited evidence on
      the efficacy of glucocorticoid injection in this condition.Trigger finger usually
      results from tendon entrapment beneath a thickened A1 flexor pulley. An
      association with hand tool use and diabetes has been shown in this condition, and
      there is evidence on the therapeutic efficacy of glucocorticoid injection. No
      other therapeutic modality has shown efficacy or has been assessed in a placebo
      controlled clinical trial in these conditions.It can be concluded that
      epicondylitis and stenosing tendinopathy are readily diagnosed, and most patients
      recover with current therapies. However, still unsolved issues preclude a purely
      evidence-based approach to these entities.

PMID- 17043460
TI  - Computed tomography does not support sacroiliitis as a feature of behcet disease:
      a metaanalytic review.

PMID- 17043461
TI  - Osteonecrosis of the femoral head resulting from excessive corticosteroid nasal
      spray use.

PMID- 17043462
TI  - The coincidence of ankylosing spondylitis and gouty arthritis.

PMID- 17043463
TI  - Successful use of etanercept in a patient with pyoderma gangrenosum complicating
      rheumatoid arthritis.

PMID- 17043464
TI  - The prevalence and clinical impact of reported cognitive difficulties (fibrofog)
      in patients with rheumatic disease with and without fibromyalgia.
AB  - Cognitive dysfunction in patients with rheumatic disease encompasses a range of
      impairment. Their prevalence, co-occurrence, and impact on symptom severity were
      assessed in 57 patients with fibromyalgia (FMS) and 57 patients with rheumatic
      disease without FMS. Information pertaining to memory decline, mental confusion,
      and speech difficulty was extracted from questions embedded in a health
      questionnaire and a blind retrospective chart review. Pain, morning stiffness,
      fatigue, and sleep difficulty were established on a 0- to 100-mm visual analog
      scale. Variables of mental confusion, fatigue, tension, depression, anger, and
      vigor were assessed using the Profile of Mood States.Compared with the non-FMS
      sample, patients with FMS complained more often of memory decline (70.2-24.6%),
      mental confusion (56.1-12.3%), and speech difficulty (40.4-3.5%). Memory decline
      and mental confusion were coupled more often in patients with FMS (50.9-8.8%).
      Patients with FMS with this combination of cognitive problems reported more pain
      (76.0-45.4%), stiffness (79.7-43.7%), fatigue (79.6-52.6%), and disturbed sleep
      (59.2-36.6%) compared with patients with FMS with memory problems alone. Patients
      with rheumatic disease substantially differ in cognitive vulnerability, with
      patients with FMS at considerably higher risk for cognitive difficulty. More
      importantly, the prevalence of a combined disturbance in memory and mental
      clarity is high and closely associated with the perception of increased illness
      severity and diminished mental health in FMS. That this linkage has the
      possibility of having a great deal to do with an important clinical variant of
      FMS underscores the need for greater clinical recognition of this underrecognized
      pattern and for further research.Patients with fibromyalgia frequently report
      memory and concentration problems, especially if asked about them. Clinicians
      could judge these complaints as similar to adult attention deficit syndrome and
      reassure the patient. Trying medication to improve attention and concentration is
      sensible but untested in fibromyalgia.

PMID- 17043465
TI  - Pilot investigation of hyaluronate injections for first metacarpal-carpal (MC-C)
      osteoarthritis.
AB  - Hyaluronate intraarticular injections are widely used for treatment of pain
      associated with osteoarthritis of the knee, but there is no published literature
      on its use in osteoarthritis of the hand. We describe an open-label, baseline
      controlled pilot study in which 5 weekly injections of 10 mg sodium hyaluronate
      (molecular weight 500-730 kDa) in 1 mL was used to treat 16 patients with
      osteoarthritic first metacarpal-carpal (MC-C) joints. The injections were
      performed easily and were well tolerated. Mean pain score at 5 months after the
      last injection, on a 10-point visual analog scale, decreased from 4.74 to 2.56 at
      rest. Pain on use decreased from 5.91 to 4.33. Pinch strength and a short
      questionnaire on hand function did not significantly change. The results of this
      small pilot study suggest that intraarticular injections into the first MC-C
      joint are easily administered, well tolerated, and could be an effective
      treatment option for patients with osteoarthritis of this joint. Further
      investigation using larger, blind controlled clinical studies are warranted.

PMID- 17043467
TI  - Inflammatory arthritis of the hands as expressed by the impressionists in the
      Orsay Museum.
AB  - An extensive study looking for signs of inflammatory arthritis in the paintings
      of the impressionists was performed at the Orsay Museum in Paris, France. Of the
      435 paintings reviewed, 3 works by different painters were found to show signs of
      inflammatory arthritis of the hands. We suspect that the importance of the
      arthritis in the models' lives led the painters to emphasize this condition in
      their paintings.

PMID- 17043468
TI  - Coronary vasculitis with acute myocardial infarction in a young woman with
      systemic lupus erythematosus.
AB  - Myocardial infarction in patients with systemic lupus erythematosus (SLE) is most
      commonly a consequence of atherosclerosis. Coronary vasculitis with aneurysms is
      a rare cause of myocardial ischemia in SLE. We present a case of a 22-year-old
      woman with a 4-year history of SLE who was admitted with acute onset of chest
      pain. Although initially treated for lupus pericarditis, she was subsequently
      found to have an acute myocardial infarction. Cardiac catheterization revealed
      multiple areas of aneurysmal coronary dilatation and only moderate stenoses of
      the secondary branches.In view of the angiographic findings, coronary
      revascularization was not indicated. Anticoagulant therapy was initiated as a
      result of the presence of large aneurysmal coronary dilatations, which are
      predisposed to in situ thrombosis and distal embolization. The coronary
      vasculitis was treated with immunosuppressive therapy. Measures aimed at
      secondary prevention of coronary artery disease, including optimization of lipid
      profile, blood pressure control, and prevention of left ventricular postinfarct
      remodeling, were initiated and continued indefinitely.

PMID- 17043469
TI  - Whipple disease revisited: radiographic features of a patient with 35 years of
      undiagnosed arthritis.
AB  - Whipple disease is a relatively rare systemic disorder with protean
      manifestations among which arthropathic involvement is a frequently attendant and
      early manifestation. We report the second of 2 consecutively diagnosed Whipple
      patients seen in an outpatient rheumatology practice who exhibited the triad of
      the singularly seldom reported radiographic findings of sacroiliitis, cervical
      apophyseal fusion, and pancarpal narrowing is reported. Both unexplained
      recurrent arthritis and these radiographic features should lead one to consider
      this treatable disease.

PMID- 17043470
TI  - Spinal gout: case report and review of the literature.
AB  - Spinal involvement is considered to be a rare complication of gout. We report a
      case of a 48-year-old woman with chronic tophaceous gout, recently desensitized
      to allopurinol, who presented with an L4 radiculopathy. A magnetic resonance
      image (MRI) of the lumbosacral spine revealed an extradural process at L4 level.
      Three months before this episode, for unrelated reasons, the patient had an MRI
      of her entire spine, which was normal. Laminectomy was performed revealing a
      large gouty tophus. The fact that a large gouty tophus formed over this short a
      period of time causing neurologic symptoms highlights the importance of
      aggressive medical management of patients with longstanding tophaceous gout with
      urate-lowering agents. Spinal extradural gout could lead to neurologic deficits
      necessitating emergent surgery for decompression, exposing the patient to further
      risk. Every effort should be made to lower the serum uric acid level by
      maximizing the pharmacologic regimen and, if necessary, desensitizing the
      patient, like in our case, if there is a history of allergy to allopurinol.

PMID- 17043471
TI  - Benign angiopathy of the central nervous system.
AB  - Apparent central nervous system vasculitis could have a benign course in a subset
      of patients and is referred to as benign angiopathy of the central nervous system
      (BACNS). This is mostly is seen in young women and presents with acute onset of
      neurologic symptoms, usually in the form of severe headache and/or a focal
      neurologic event. Cerebrospinal fluid analysis could be normal or nearly normal.
      Brain angiogram typically shows segmental narrowing, ectasia, or beading in
      multiple vascular territories on brain angiogram. Like in all cases of CNS
      vasculitis, exclusion of other systemic diseases or its mimickers associated with
      cerebral involvement is important.BACNS could respond favorably to treatment with
      corticosteroids alone or in combination with a calcium channel blocker, thereby
      avoiding unnecessary and prolonged treatment with other immunosuppressants like
      cyclophosphamide with their side effects. Little is published in the literature
      about BACNS, but is a rapidly emerging concept. It is thus important to
      recognize. We report a patient with classic presentation of BACNS to highlight
      the significance of distinguishing benign angiopathy from the more aggressive
      form of CNS vasculitis, because the treatment and response varies in these 2
      entities.

PMID- 17043472
TI  - Relapsing polychondritis with encephalitis.
AB  - Central nervous system manifestations are rare in patients with relapsing
      polychondritis. We report a case of encephalitis associated with relapsing
      polychondritis. The patient presented with bilateral auricular chondritis first
      and then tracheal chondritis, and encephalitis developed. The symptoms and signs
      of encephalitis were felt mostly likely to be the result of vasculitis and
      improved dramatically after pulse corticosteroid therapy. We believe that early
      recognition of central nervous system involvement in relapsing polychondritis is
      extremely important. High-dose corticosteroids should be given to suspected cases
      as early as possible.

PMID- 17043473
TI  - Beaver fever arthritis.
AB  - Giardia lamblia, a flagellated protozoan and common cause of gastroenteritis, is
      a rare but previously reported cause of reactive arthritis (ReA). We report a
      case of inflammatory oligoarthritis in a young woman after infection with
      Giardia. Two weeks after being treated, she developed an inflammatory arthritis
      of her left knee and right elbow that was refractory to nonsteroidal
      antiinflammatory medication. Antinuclear antibody, rheumatoid factor, and HLA-B27
      tests were negative. She had almost immediate relief with intraarticular
      injection of corticosteroids. We review the previously reported cases of ReA
      following giardiasis and discuss possible pathogenic mechanisms. Although ReA
      most commonly occurs after chlamydial urethritis or gastroenteritis associated
      with typical enteropathic bacteria, important historical clues could point to
      less common pathogens such as Giardia. Physicians should be aware of these less
      common causes of ReA, because this could have important diagnostic and
      therapeutic implications.

PMID- 17043474
TI  - Isolated vasculitis of the cervix presenting as vaginal discharge.
AB  - A 44-year-old woman previously in excellent health presented with clear vaginal
      discharge. Pelvic examination revealed a friable cervix that showed small-vessel
      necrotizing vasculitis on cone biopsy. She had no clinical evidence of systemic
      vasculitis or any connective tissue disease. Laboratory findings of inflammation
      (raised erythrocyte sedimentation rate and thrombocytosis) returned to normal
      after the cone biopsy. She has been symptom-free for over 2 years after the cone
      biopsy and a subsequent hysterectomy that failed to reveal uterine vasculitis.
      Localized vasculitis of the cervix can present as vaginal discharge or
      menorrhagia without evidence of vasculitis elsewhere and does not require
      systemic therapy.

PMID- 17043476
TI  - Nocturnal neck pain relieved by aspirin.

PMID- 17043475
TI  - The ACRONYM project.

PMID- 17043477
TI  - The use of infliximab in a patient with steroid-dependent Churg-Strauss syndrome.

PMID- 17043478
TI  - Women's Health Initiative perspective: what does it really mean to the
      rheumatologist?

PMID- 17043479
TI  - How many versions and translations of the HAQ and its variants are needed? It
      doesn't matter-just use one.

PMID- 17043480
TI  - Metabolic syndrome and ischemic heart disease in gout.
AB  - BACKGROUND: For decades, gout has been associated with several metabolic
      abnormalities and with ischemic heart disease (IHD). OBJECTIVE: Our aim was to
      determine the prevalence of metabolic syndrome by Adult Treatment Panel III
      criteria (ATP III) and ischemic heart disease (IHD) by electrocardiogram (EKG)
      and/or single photon emission computed tomography (SPECT) in patients with gout.
      METHODS: We included 64 consecutive outpatients with primary gout, but no history
      of IHD, attending our clinic for the first time. Demographic and clinical data
      were recorded and resting electrocardiogram, lipid profile, fasting insulin, and
      SPECT with Tc sestamibi were performed. Metabolic syndrome was defined according
      to ATP III criteria (> or =3 of the following data: 1) hyperglycemia (fasting
      glucose > or =110 mg/dL) or previous diagnosis of diabetes mellitus, 2)
      hypertension (> or =130/85 mm Hg) or previous diagnosis, 3) high-density
      lipoprotein (HDL) <40 mg/dL (men) or <50 mg/dL (women), 4) triglycerides > or
      =150 mg/dL, and 5) obesity. RESULTS: IHD was diagnosed in 10 patients (16%); 2
      had EKG changes compatible with previous silent myocardial necrosis and the other
      8 had abnormal SPECT. The prevalence of metabolic syndrome was 82%, all patients
      had at least 1 metabolic abnormality, but all the patients with IHD had metabolic
      syndrome (3 criteria according with ATP III). Patients with IHD differed from
      those without IHD in the percentage of HDL levels <40 mg/dL (100% vs. 82%; P =
      0.05) as well as glucose and insulin levels in the fasting state (129.3 +/- 6.1
      mg/dL vs. 92.7 +/- 16.7 mg/dL; P = 0.000; and 21.1 +/- 6.0 vs. 17.5 +/- 8.6
      UI/mL; P = 0.03) and low-density lipoproteins (143.9 +/- 21.3 mg/dL vs. 118.2 +/-
      47.7 mg/dL; P = 0.014). In contrast, serum creatinine and urea (1.02 +/- 0.13
      mg/dL vs. 1.5 +/- 1.5 mg/dL; P = 0.024; and 33.9 +/- 9.3 mg/dL vs. 48.7 +/- 46.1
      mg/dL; P = 0.039) and creatinine clearance <50 mL/min (10% vs. 37%; P = 0.06)
      were higher in patients without IHD. CONCLUSIONS: In this work, metabolic
      syndrome was very common among patients with gout. Sixteen percent of the
      patients, although previously asymptomatic, had IHD, they all had metabolic
      syndrome. Gouty patients frequently first seek medical care from a
      rheumatologist. The rheumatologist can have an important role in detecting
      metabolic syndrome and risk factors for cardiovascular disease.

PMID- 17043481
TI  - Validation and crosscultural adaptation of an argentine spanish version of the
      health assessment questionnaire disability index.
AB  - BACKGROUND: The Health Assessment Questionnaire (HAQ) is one of the most
      frequently used instruments to assess functional capacity in activities of daily
      living. OBJECTIVE: The objective of our study was to determine the
      reproducibility and validity of an Argentinean version of the HAQ disability
      index (HAQ-DI) in patients with rheumatoid arthritis (RA). METHODS: Consecutive
      adult patients with RA from 3 different provinces in Argentina were included. The
      original English version of the HAQ-DI was translated and adapted into Spanish by
      3 rheumatologists and the final version back translated into English by a
      bilingual person. The reproducibility of the questionnaire was assessed in 30
      patients who came for a second visit 3 to 5 days later. The cross-sectional
      construct validity was assessed by comparing the HAQ with classic parameters of
      disease activity (number of swollen and tender joints, patient and physician
      visual analog scale for pain and activity as well as functional class,
      erythrocyte sedimentation rate, and C-reactive protein. RESULTS: Two hundred
      patients with RA were included. The reproducibility was r = 0.97 (P = 1 x 10-5);
      intraitem correlation analysis did not show any redundancy. Correlation between
      HAQ-A and parameters of disease activity were all significant. A stepwise
      multiple regression analysis showed that the main variables associated with HAQ-A
      scores were visual analog scale for pain and duration of morning stiffness. A
      weak although significant negative correlation was found between the HAQ-A and
      economic level (r = -0.21, P = 0.03). The median time to complete the
      questionnaire was 5 minutes and there were no problems with any questions.
      CONCLUSION: This version of the HAQ-DI would allow for more availability so that
      Spanish-speaking countries can select the version most suitable to their
      sociocultural environment.

PMID- 17043482
TI  - How valuable is screening for thyroid disease in patients with carpal tunnel
      syndrome?
AB  - BACKGROUND: It has been suggested that many patients with carpal tunnel syndrome
      have associated thyroid or other metabolic diseases. METHODS: 206 patients with
      clinical features suggestive of carpal tunnel syndrome (CTS), including those
      with known underlying cause of CTS, were screened for thyroid dysfunction. Nerve
      conduction studies were compatible with a diagnosis of CTS in 136 patients (CTS
      group). RESULTS: We diagnosed only 2 new cases of hypothyroidism (1.5% of
      patients in the CTS group) and none with hyperthyroidism. CONCLUSIONS: Thus
      routine screening of patients with isolated CTS for thyroid function abnormality
      does not appear to be worthwhile.

PMID- 17043483
TI  - Sepsis as a possible adverse drug reaction in patients with rheumatoid arthritis
      treated with TNFalpha antagonists.
AB  - BACKGROUND: Clinical improvement during the treatment of rheumatoid arthritis
      (RA) with the TNFalpha antagonists has been well documented. Our knowledge of
      uncommon adverse drug reactions (ADRs) with these new drugs is more restricted.
      Concerns have been raised that these types of drugs could cause an increased
      frequency of infections, and already existing infections are named as
      contraindications in the product labels. METHODS: In Sweden, it is compulsory for
      healthcare professionals with permission to prescribe drugs to report suspected
      ADRs to the regulatory authority, the Medical Product Agency (MPA). At the 6
      regional centers that are established in Sweden, a preliminary causality
      assessment is made and the data is transferred online to a database. RESULTS:
      Between January 1, 1999, and June 30, 2003, 29 cases of sepsis were reported as
      suspected adverse effects caused by drugs. Seventeen of these cases concerned
      TNFalpha antagonists. The MPA has received 3 reports of septicemia in patients
      from Northern Sweden treated with the TNFalpha antagonist etanercept. In
      submitting these reports, factors that can contribute to susceptibility and to
      more fatal courses of serious infections are taken into consideration.
      Demographic and pharmaceutical factors as well as risks from predisposing
      conditions are discussed in connection with the cases in this report. CONCLUSION:
      There is a need for more information to physicians to be aware of sepsis as a
      possible and serious ADR during treatment with TNF antagonists, and that patients
      with predisposing diseases or those who do not regularly visit their
      rheumatologist could be at higher risk.

PMID- 17043484
TI  - Evidence-based soft tissue rheumatology: III: trochanteric bursitis.
AB  - Trochanteric bursitis is a term used to name a syndrome that features pain and
      tenderness over the greater trochanter. Present evidence suggests that in the
      majority of cases, symptoms result from pathology of the gluteus medius or
      minimus muscles rather than a bursa. Lower limb length discrepancy, iliotibial
      band contracture, hip osteoarthritis and lumbar spondylosis are often mentioned,
      but no proved as predisposing factors. After a lumbar spine or hip and other
      local pathology have been considered and clinically excluded, the clinical
      features of the syndrome, ie lateral location of pain plus characteristic
      trochanteric tenderness are usually sufficient to reach a diagnosis. Most
      patients with trochanteric bursitis can be successfully treated with a NSAID,
      physiotherapy plus a local corticosteroid injection. The few refractory cases are
      often treated surgically. Disappointingly, none of the therapeutic interventions
      used in trochanteric bursitis have been validly assessed.

PMID- 17043485
TI  - Cardiac tamponade: an uncommon presentation of hypertensive scleroderma renal
      crisis.
AB  - Cardiac tamponade is an extremely rare manifestation of systemic sclerosis and
      has been reported to be a risk factor for the subsequent development of renal
      failure. We report the case of a 37-year-old man with recently diagnosed
      scleroderma who presented with chest pain and shortness of breath. He was found
      to have scleroderma renal crisis as well as cardiac tamponade. He responded
      hemodynamically to emergent pericardiocentesis and blood pressure control with
      angiotensin-converting enzyme inhibitors. However, the renal function
      deteriorated further leading to development of end-stage renal disease and
      required chronic hemodialysis.Although pericardial effusions are common in
      scleroderma, cardiac tamponade is rare. Coexistent hypertension and cardiac
      tamponade in scleroderma have not been described previously. Elevated systemic
      blood pressure can accompany and should not be used to exclude the diagnosis of
      cardiac tamponade. We emphasize the importance of pericardial disease as an
      uncommon but important cause of chest pain in patients with scleroderma.

PMID- 17043486
TI  - Pulmonary capillaritis and hemorrhage in neonatal lupus erythematosus (NLE).
AB  - We describe the case of an infant who presented to our institution with
      tachypnea, cough, and hypoxemia. The baby had been diagnosed with complete heart
      block (heart rate 50-60 beats/min) in utero and had a pacemaker placed at birth.
      The mother was found to have both anti-Ro and anti-La antibodies. At age 3
      months, the chest radiograph showed diffuse bilateral interstitial infiltrates. A
      lung biopsy confirmed the presence of necrotizing capillaritis and alveolar
      hemorrhage, which is an infrequent complication in pediatric patients with
      systemic lupus erythematosus. The patient did well after recognition and
      aggressive treatment of this previously unrecognized complication of neonatal
      lupus.

PMID- 17043487
TI  - Infliximab treatment of Familial Mediterranean fever and its effect on secondary
      AA amyloidosis.
AB  - We describe a patient with a long history of familial Mediterranean fever who
      developed proteinuria as a result of secondary AA amyloidosis. In this patient,
      the inflammatory process, including recurrent attacks of arthritis, abdominal
      pain, nephrotic syndrome secondary to amyloidosis, and high sedimentation rate,
      was rapidly suppressed by treatment with infliximab and there was remarkable
      improvement of the proteinuria.Because TNF-alpha is a proinflammatory cytokine
      that plays a major role in FMF and secondary amyloid, it is an appropriate target
      for therapy. Our case is the first case of reactive systemic amyloidosis
      secondary to familial Mediterranean fever, which responded favorably to
      infliximab.

PMID- 17043488
TI  - Histoplasmosis with tenosynovitis of the hand and hypercalcemia mimicking
      sarcoidosis.
AB  - We report on an otherwise healthy 47-year-old male who developed subacute
      tenosynovitis of the hand associated with night sweats and inguinal
      lymphadenopathy. He had a past history of granulomatous mediastinal lymphadenitis
      with positive histoplasmosis serology 11 years previously. Carpal tunnel
      exploration with biopsy demonstrated granulomatous inflammation. Granulomatous
      inflammation, hypercalcemia, and an elevated serum angiotensin converting enzyme
      (ACE) level suggested the diagnosis of sarcoidosis, however histoplasmosis
      infection could eventually be diagnosed. This unusual presentation of
      histoplasmosis underscores the fact that the diagnosis of sarcoidosis requires
      careful exclusion of other causes of granulomatous inflammation, particularly
      infectious agents. Even in the setting of an elevated ACE level and
      hypercalcemia, the possibility of an infectious etiology must be considered
      before establishing a diagnosis of sarcoidosis.

PMID- 17043489
TI  - Molecular biology and immunology for clinicians 29: lipid domains, lipid rafts,
      and caveolae.
AB  - The development of an antigen-specific immune response depends on the peptide
      loaded MHC molecule on the surface of the antigen-presenting cell being found by
      the antigen-specific receptor on the cell about to be activated (the T-cell
      antigen receptor for T-cells or the membrane-bound immunoglobulin molecule on B
      cells). The details of this process are becoming clear now with the appreciation
      of the supramolecular organization of the structures that make this cell-cell
      interaction. In the last 6 years has come an appreciation of the heterogeneity of
      the lipid bilayer membrane (a concept first put forth over 20 years ago), with
      certain lipids and membrane-bound proteins segregating into discrete ships called
      "lipid rafts" sailing in the surrounding more liquid lipid bilayer membrane.
      Knowledge of these microscopic structures leads to a better understanding of how
      antigen-specific responses are triggered and how aberrant responses are avoided;
      as one leader in the field put it, "keeping T-cells rested but ready."Membrane
      heterogeneity directly contributes to the rapid development of a more formalized
      cell-cell interaction that has been termed the "immunologic synapse." It is at
      this synapse that the acquired immune response, antigen specificity, is learned.
      In addition to antigen presentation, lipid rafts have also been implicated in
      signaling through a large number of receptors, endocytosis, cell interactions
      with pathogens and toxins, budding of viruses from host cell membrane, and the
      pathogenesis of prion disorders. Yet again, an insight in one discrete field of
      cell biology is proving to be of great relevance in a host of other areas of
      study.

PMID- 17043490
TI  - Popliteal artery entrapment with peripheral thromboembolism.

PMID- 17043491
TI  - Rheumatology retrospective.

PMID- 17043492
TI  - 'Fibrophagia': pathophysiology and treatment.

PMID- 17043494
TI  - A pathophysiologic approach to the clinical management of arthritis and pain:
      current and future implications.

PMID- 17043493
TI  - Is rituximab a potential new therapy in systemic sclerosis? new evidence
      indicates the presence of CD20-positive B-lymphocytes in scleroderma skin.

PMID- 17043495
TI  - Prostaglandins: modulators of inflammation and cardiovascular risk.
AB  - Cyclooxygenase (COX)-2-specific drugs such as rofecoxib and celecoxib and the
      newer agents, etoricoxib and valdecoxib, were developed to provide a safer
      alternative to traditional nonsteroidal antiinflammatory drugs (tNSAIDs). These
      drugs have been shown significantly to reduce endoscopically visualized
      gastrointestinal ulcers, and one of them, rofecoxib, has demonstrated a 50%
      reduction in clinically important gastrointestinal outcomes compared with a
      tNSAID. However, COX-derived prostaglandins also have complex interactions with
      the cardiovascular system. This article briefly reviews our current understanding
      of the interactions between prostaglandins and cardiovascular physiology, and
      addresses some of the concerns that recently have been raised regarding coxibs
      and the risk of cardiovascular events.

PMID- 17043496
TI  - Management strategies for osteoarthritis, ankylosing spondylitis, and gouty
      arthritis.
AB  - Rheumatic diseases are among the most frequent causes of pain and disability.
      Effective management of rheumatic diseases including osteoarthritis (OA),
      ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the
      underlying disease mechanisms.Symptoms of OA result from both mechanical factors
      and elements of inflammation. Current management strategies target both of these
      factors and generally consist of nonpharmacologic and pharmacologic
      interventions, including use of nonspecific nonsteroidal antiinflammatory drugs
      (NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic
      and antiinflammatory properties. Other approaches include intraarticular
      hyaluronate and the use of alternative therapies under investigation such as
      acupuncture or glucosamine.Disease mechanisms in AS involve enthesitis, an
      inflammation at the site of insertion of ligaments, tendons, or joint capsules to
      bone. Posture and exercise are important nonpharmacologic strategies that may be
      made easier with the use of NSAIDs or coxibs. Recently developed therapies,
      including tumor necrosis factor inhibitors, target the underlying disease
      mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying
      effects still need to be established.In gout, hyperuricemia leads to crystal
      induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has
      shown promise in treating acute gout, with efficacy similar to indomethacin, the
      current standard NSAID often used in these patients. Oral or intraarticular
      steroids can also be considered. For chronic care uricosurics can be beneficial
      if renal function is normal and excretion is not excessive, but allopurinol is
      used most often. Nonpharmacologic modalities, such as rest and cold applications,
      are useful for acute episodes, and lifestyle modification in the form of diet can
      also play a role in chronic disease management.

PMID- 17043498
TI  - A pathophysiologic approach to the clinical management of arthritis and pain:
      current and future implications.

PMID- 17043497
TI  - Pathogenesis of rheumatoid arthritis.
AB  - Although widely diverse mechanisms have been held responsible for tissue damage
      in rheumatoid arthritis (RA), it is likely that immune complexes are the
      underlying cause. Self-aggregating complexes of 7s rheumatoid factors in synovial
      fluid are a distinguishing feature of RA, whilst circulating complexes of 19s
      rheumatoid factor directed against the hinge region of 7s immunoglobulins are
      perhaps less specific. Other autoimmune complexes, such as those containing
      antibodies directed against citrullinated peptides, have been identified and may
      be more specific for RA, although the antigens against which these antibodies are
      directed have not been fully characterized. Together with phagocytic cells such
      as neutrophils, immune complexes are critical to the pathogenesis of RA; their
      effects are mediated by a complex cascade involving complement activation and
      stimulation of phagocytes via C5a and Fc receptors. These mechanisms result in a
      release of mediators of inflammation and joint destruction: cytokines,
      metalloproteinases, and reactive oxygen intermediates. This article will review
      recent, and some not too recent, progress made towards working out the
      pathogenesis of RA.

PMID- 17043499
TI  - Biologic therapies on the horizon for rheumatoid arthritis.
AB  - Recent research on rheumatoid arthritis (RA) has broadened our understanding of
      this disease, and mediators of the disease process have been identified as
      potential therapeutic targets. A series of novel agents have been developed
      specifically targeting these mediators and are collectively referred to as
      biologic response modifiers or biologic agents. A number of these agents have
      been introduced into clinical practice or are currently in clinical trials.
      Agents that have been approved include 2 monoclonal antibodies and a receptor
      fusion protein, all of which target tumor necrosis factor (TNF), as well as an
      inhibitor of interleukin-1 (IL-1). Other areas that are currently being
      investigated are new methods of blocking TNF and other cytokines, including IL-1
      and IL-6. Emerging data also suggest that both T and B cells have critical roles
      in the pathogenesis of RA and could provide rational targets for therapy.
      Additionally, the role of adhesion molecules in RA continues to expand, and
      several agents have been proposed as potential therapies. These rapid advances in
      our understanding of RA and their implications for rationally targeted therapies
      are reviewed.

PMID- 17043500
TI  - JCR Journal Supplement CME Questions.

PMID- 17043501
TI  - Activity evaluation.

PMID- 17043502
TI  - Faculty evaluation/request for credit.

PMID- 17043503
TI  - Mechanisms of inflammatory pain: therapeutic implications.
AB  - The study and treatment of clinical pain has historically identified particular
      pain syndromes and linked their etiology with disease factors. Missing in this
      approach is consideration of the mechanisms accounting for the pain that is
      experienced by the patient. The recent increase in our understanding of how
      peripheral and central mechanisms contribute to the perception of pain, including
      the identified role of prostaglandins, has led to a shift in treatment strategy
      to directly target these mechanisms. This article provides a brief overview of
      pain mechanisms, focusing on inflammatory pain, and discusses the role of
      cyclooxygenase (COX)-2 inhibitors as analgesic agents.

PMID- 17043504
TI  - Informed choices in anti-inflammatory drug therapy: why patient risk matters.

PMID- 17043505
TI  - Infliximab Therapy for Patients With Active and Refractory Spondyloarthropathies
      at the Dose of 3 mg/kg: A 20-Month Open Treatment.
AB  - BACKGROUND: : Infliximab at the dose of 5 mg/kg per infusion has been shown
      effective for the treatment of active spondyloarthropathies. It is not clear if
      the 5 mg/kg is required in most patients. OBJECTIVE: : To evaluate the long-term
      efficacy and safety of infliximab at the lower dose of 3 mg/kg in patients with
      active and refractory ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
      METHODS: : Thirty patients were enrolled in a 78-week, single-center,
      prospective, open-label pilot study, including 16 patients with severe and active
      AS and 14 patients with active and refractory PsA. Infliximab (3 mg/kg, in
      combination with a stable dose of methotrexate was administered intravenously at
      0, 2 and 6 weeks, and q8 weeks thereafter (schedule-A) and the improvement of
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; for AS patients) and
      Patient Global Assessment of Disease Activity (PDA; for PsA patients) was
      monitored at baseline and at every visit (primary variables). Patients who did
      not respond sufficiently at 14 weeks, as well as patients who relapsed at any
      time during follow-up, received infliximab every 4 weeks (treatment schedule-B).
      Three different statistical approaches (per-protocol, last observation carried
      forward and by intention-to-treat) were applied. RESULTS: : Ten patients
      discontinued treatment for various reasons, including 3 (10.0%) because of
      allergic reactions. Twenty patients (66.7%, 9 with AS and 11 with PsA) had
      completed 78 weeks of treatment (schedule-A, 11 patients; schedule-B, 9
      patients). Of these patients, 18 (90.0%) showed optimal response (improvement
      >/=50%), including 13 (65.0%) with improvement >/=70%. ASsessments in AS (ASAS)
      50% was attained by 7/9 AS patients (77.8%). At 78 weeks of treatment,
      statistically significant improvement of indices of disease activity, function
      and quality of life was observed by all statistical approaches applied.
      CONCLUSIONS: : Infliximab at 3 mg/kg every 8 weeks or, if needed, every 4 weeks
      appears to be an effective and rather safe treatment of patients with active and
      refractory AS and PsA after 78 weeks of treatment.

PMID- 17043506
TI  - Successful Treatment of Dry Mouth and Dry Eye Symptoms in Sjogren's Syndrome
      Patients With Oral Pilocarpine: A Randomized, Placebo-Controlled, Dose-Adjustment
      Study.
AB  - BACKGROUND: : Sjogren's syndrome is characterized by the presence of xerostomia
      and/or xerophthalmia. Pilocarpine, a muscarinic cholinergic agonist, has been
      proven to be efficacious in treating radiation-induced xerostomia (up to 30
      mg/day) and symptoms of dry mouth in Sjogren's patients (up to 20 mg/day).
      OBJECTIVE: : To compare the safety and efficacy of oral pilocarpine (dose
      adjusted) versus placebo in the treatment of dry eye and dry mouth symptoms in
      Sjogren's syndrome at 6 and 12 weeks. METHODS: : In this 11-center, 256-patient
      placebo-controlled study, the safety and efficacy of oral pilocarpine (20 mg to
      30 mg daily) for relief of Sjogren's-related dry mouth and dry eye symptoms was
      assessed. Changes in symptoms and salivary flow were measured over 12 weeks.
      RESULTS: : Compared with placebo, salivary flow was significantly increased in
      the pilocarpine group (P</= 0.0001) after the first dose and throughout the
      study. Significant improvement in patients' global assessment of dry mouth (P</=
      0.0001) with relief in 5 of 7 separate oral symptoms (P</= 0.02) was reported by
      the treated patients throughout study. Minimal differences in 3 of 8 ocular
      symptoms were noted at 6 weeks (5-mg dose), but at 12 weeks (5- to 7.5-mg dose),
      the pilocarpine group demonstrated both significant improvement in global
      assessment of dry eyes (P</= 0.0001) and relief in 6 of 8 related symptoms (P</=
      0.04). The drug was well tolerated at both doses. The most common pilocarpine
      related side effects were sweating, urinary frequency, flushing, and chills.
      CONCLUSIONS: : Significant relief in dry mouth symptoms was noted at 20 mg/day,
      and significant relief in ocular symptoms, including lower artificial tear
      requirement, was noted after the dose was increased to 30 mg/day.

PMID- 17043507
TI  - Risk of Upper Gastrointestinal Injury and Events in Patients Treated With
      Cyclooxygenase (COX)-1/COX-2 Nonsteroidal Antiinflammatory Drugs (NSAIDs), COX-2
      Selective NSAIDs, and Gastroprotective Cotherapy: An Appraisal of the Literature.
AB  - Numerous studies using varying methodologies and outcome measures have examined
      the gastrointestinal risks of aspirin and nonaspirin nonsteroidal
      antiinflammatory drug (NSAID) use. Despite the large volume of literature,
      clarity regarding the key risk factors and their quantitative importance is
      lacking. We performed a comprehensive review of the literature to summarize the
      incidence of gastrointestinal injury in populations with varying risk
      characteristics using agents that inhibit both isoforms of cyclooxygenase and
      those that selectively inhibit only cyclooxygenase-2 (COX-2).Although risk
      estimates vary, the risk of serious gastrointestinal complications in NSAID users
      is approximately 2.5 to 4.5 times that of nonusers. The risk of NSAID-related
      gastrointestinal bleeding is augmented by concomitant low-dose aspirin and could
      approach double the risk of NSAID use alone. The preponderance of evidence shows
      that the risk of NSAID-related gastrointestinal bleeding is reduced approximately
      50% with a coxib as compared with traditional NSAID. The relative risk of
      hospitalization resulting from upper gastrointestinal bleeding for patients
      treated with a nonselective NSAID was 4.4 (95% confidence interval [CI], 2.3-8.5)
      and 1.9 (95% CI, 1.0-3.5) when compared with celecoxib and rofecoxib,
      respectively. Aspirin increases the risk of NSAID-related gastrointestinal
      bleeding in patients taking COX-2 selective inhibitors, with odds ratios ranging
      from 5.8 to 7.7; however, it is unknown whether this risk is greater than the
      risk from aspirin alone. The risks from both traditional NSAIDs and COX-2
      inhibitors are increased in the elderly, patients on anticoagulation, and
      patients with prior gastrointestinal events.Gastroprotective agents have been
      found to significantly reduce the risk for gastrointestinal injury in patients
      receiving NSAID therapy, especially those receiving concurrent low-dose
      cardioprotective doses of aspirin. Proton pump inhibitors (PPIs) and misoprostol
      both reduce the incidence of gastric and duodenal ulcers, as well as recurrence
      of ulcer complications in patients receiving NSAIDs. The relative risk for
      gastric ulcers ranged from 0.17 to 0.38, whereas for duodenal ulcers, the range
      was 0.11 to 0.28. Although misoprostol is slightly more effective in preventing
      gastric ulcers in these patients, PPIs are better tolerated. Although NSAIDs
      appear safe in "low-risk" populations, our review suggests that the use of
      gastroprotective cotherapy should be considered in patients at higher risk of
      NSAID-related upper gastrointestinal bleeding.

PMID- 17043508
TI  - Dosing of antirheumatic drugs in renal disease and dialysis.
AB  - Many patients with rheumatic diseases have their management complicated by renal
      problems. Renal failure modifies the metabolism of many drugs, especially by
      retention. Questions often arise about the effects of renal failure on the
      handling of drugs commonly used in rheumatology. For which drugs must we be
      especially concerned about increased toxicity? Patients on chronic dialysis may
      also need a variety of drugs for rheumatic disease. How are our drugs dialyzed,
      and which of these can be safety used and how best to use them?Decisions about
      dosing of rheumatic drugs are often required for the patients with chronic renal
      insufficiency or on long-term dialysis, although many drugs have not been
      formally studied in these settings. Patients with renal insufficiency are
      excluded from most drug trials. Data for some of these drugs have to be
      extrapolated based on the information available about the pharmacokinetics of the
      drug.This review addresses dosing of commonly used drugs in rheumatology in
      patients with chronic renal insufficiency or failure. It is compiled from a
      MEDLINE search of papers dealing with renal handling of antirheumatic drugs and
      suggestions for dose adjustments for these drugs. Drugs reviewed include commonly
      used disease-modifying antirheumatic drugs (DMARDS), drugs used for treatment of
      gout, commonly used nonsteroidal antnflammatory drugs (NSAIDS) and the newer COX
      2 inhibitors.

PMID- 17043509
TI  - Evidence-Based Soft Tissue Rheumatology IV: Anserine Bursitis.
AB  - Anserine bursitis is a frequent cause of medial knee pain. Despite its name, the
      structure at fault causing the symptoms remains unknown. Diabetes mellitus is a
      known predisposing factor leading to the condition. Overweight and knee
      osteoarthritis are possible additional risk factors, but their role has yet to be
      assessed. Anserine bursitis is diagnosed clinically based on medial knee pain and
      localized tenderness at the inferomedial knee. Current treatment of anserine
      bursitis includes nonsteroidal anti-inflammatory dugs, physiotherapy, and local
      glucocorticoid injections. Of these, only the latter has been shown effective in
      clinical trials. Knowledge gaps in the epidemiology, pathology, and pathogenesis
      of anserine bursitis should lead to additional research efforts on this common
      and perplexing condition.

PMID- 17043510
TI  - Spontaneous pneumothorax in scleroderma.
AB  - We present an illustrative case of a patient with advanced scleroderma who
      presented with a spontaneous pneumothorax, a condition that has only rarely been
      reported previously in association with scleroderma. Our patient and those
      previously reported had advanced pulmonary fibrosis with honeycombing and
      subpleural cysts, with spontaneous pneumothorax occurring secondary to cyst
      rupture. Our patient was treated with chest tube thoracostomy, but her
      spontaneous pneumothorax later recurred. She was then treated with talc
      pleurodesis and has not had a recurrence in 18 months of follow-up.Spontaneous
      pneumothorax remains a rare pulmonary manifestation of scleroderma, occurring
      only in patients with advanced pulmonary fibrosis associated with cyst formation
      and rupture. Initial management consists of chest tube insertion, but recurrence
      is high and may require pleurodesis or partial lobectomy. Physicians managing
      patients with scleroderma should be aware of spontaneous pneumothorax, especially
      in those with advanced pulmonary fibrosis and subpleural cysts.

PMID- 17043511
TI  - Polyarteritis nodosa complicated by catastrophic antiphospholipid syndrome.
AB  - Polyarteritis nodosa (PAN) is a vasculitis of small- and medium-sized vessels,
      characterized by vascular aneurysms that can lead to ischemia and infarction. We
      present the case of a patient with classic polyarteritis nodosa in abdominal
      organs who additionally demonstrated antitreponemal and antiphospholipid
      antibodies, resulting in a severe cerebral thrombosis. This case highlights: 1.
      The potential for false-positive syphilis serology in PAN patients, and 2. The
      rare coexistence of polyarteritis nodosa and the catastrophic antiphospholipid
      syndrome.

PMID- 17043512
TI  - Avascular necrosis of bone associated with primary antiphospholipid syndrome:
      case report and literature review.
AB  - We describe, the case of a 34-year-old mestizo Mexican woman with previous
      history of fetal loss, deep vein thrombosis that developed avascular necrosis
      (AVN) of the right knee with strong positive levels of anticardiolipin antibodies
      (aCL) IgG and IgM. AVN of bone in association with aCL has been seen principally
      in systemic lupus erythematosus patients. However, few cases have been reported
      of AVN as a clinical manifestation of primary antiphospholipid syndrome. A review
      of the association of aCL and AVN in patients with systemic lupus erythematosus,
      primary antiphospholipid syndrome, and idiopathic osteonecrosis is presented.

PMID- 17043513
TI  - Treatment of resistant adult still disease with infliximab: a report of 2 cases.
AB  - Adult Still disease is characterized by high fever, arthritis, leukocytosis,
      hepatosplenomegaly, rash, and lymphadenopathy. It affects primarily young adults
      and is often disabling or even fatal. Many patients achieve long-term remissions,
      while others may develop a chronic illness refractory to multiple therapies.
      Polyarthritis or root joint involvement has been identified as a marker of
      chronic disease. No controlled studies on second-line agents have been published,
      but anecdotal studies suggest efficacy of a variety of agents including
      hydroxychloroquine, sulfasalazine, penicillamine, and methotrexate. Although
      these therapies have been used, optimal treatment of patients with resistant
      disease remains problematic. High levels of tumor necrosis factor have been
      noted, and recent report indicates etanercept may be an effective therapy. We
      report 2 cases of adult-onset Still disease resistant to NSAIDs, steroids, and
      methotrexate that have been successfully maintained on 5 mg/kg infliximab for 30
      and 29 months, respectively, with improvement of signs and symptoms despite a
      reduction of steroid dosage. In patients with resistant disease, infliximab may
      be a safe, effective agent. Its use in this disease merits further study.

PMID- 17043515
TI  - Thomas sydenham (1624-1689), on gout: 1717.

PMID- 17043514
TI  - Basic science for the clinician 28: T-helper cell subtypes.
AB  - The immune response is finely tuned to the various invaders that may cause damage
      and disease. There is an innate immune system and an acquired immune response,
      but there is much overlap and recruitment across these lines of demarcation.
      Broadly speaking, there are cellular immune responses (cellular effectors that
      identify intracellular pathogens and damage and kill the affected cell) and
      humoral (B cells become plasma cells which make antibodies to bind extracellular
      pathogens and their products) that draw upon both systems. At the pivotal point,
      where decisions are made whether to mount a primarily cellular or a humoral
      response are T-helper cells (CD4). As you may have read, CD4 cells come in at
      least 2 subtypes: TH1 cells predispose to the development of a primarily cellular
      responses and TH2 predispose to humoral responses. Not very complicated, but
      worthy of some discussion to look at the cytokines produced, the changes these
      cytokines evince, and how the balances (dare I say yin and yang) keep us healthy
      but also may get us into trouble!

PMID- 17043516
TI  - Fever therapy for arthritis.

PMID- 17043517
TI  - Bradycardia due to Methylprednisolone Therapy.

PMID- 17043518
TI  - An Ayurvedic-derived osteoarthritis treatment - what can this teach us?

PMID- 17043519
TI  - Scleroderma renal crisis: the sword of damocles.

PMID- 17043520
TI  - A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an
      Ayurvedic drug, on osteoarthritis of the knees.
AB  - BACKGROUND: The ancient Indian (Asian) Ayurvedic medicinal system uses
      herbomineral drugs to treat arthritis. Despite centuries of use, very few have
      been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant
      Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
      Curcuma longa) is currently used to treat arthritis. OBJECTIVE: The objective of
      this study was to evaluate the efficacy and safety of RA-11 in patients with
      symptomatic osteoarthritis (OA) of the knees. METHODS: A total of 358 patients
      with chronic knee pain were screened free-of-cost in "arthritis camps" in an
      Indian metropolis. Ninety patients with primary OA of the knees (ACR
      classification; Arthritis Rheum 1986;29:1039-1049) were found eligible
      (postanalgesic washout pain visual analog score [VAS] > or =40 mm in either or
      both knees on body weight-bearing activities) to enroll into a randomized, double
      blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial
      (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent
      analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
      allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
      practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
      patient during the preceding 48 hours) and modified WOMAC (Western Ontario
      McMaster University OA Index, Likert scale, version 3.0) were the primary
      efficacy variables. The WOMAC section on "physical function difficulty" was
      modified for Indian use and validated before the trial. Routine laboratory
      testing was primarily done to monitor drug safety. At baseline, the groups
      (active = 45, placebo = 45) were well matched for several measures (mean pain
      VAS: active = 6.17; placebo = 6.5). RESULTS: 1) EFFICACY: Compared with placebo,
      the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week
      32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05,
      analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC
      scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA)
      in the active group. 2) SAFETY: Both the groups reported mild adverse events (AE)
      without any significant difference. 3) Withdrawals: Twenty-eight patients were
      discontinued. None reported drug-related toxicity. The majority failed follow
      up/compliance. No differences were observed between the groups. CONCLUSION: This
      controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in
      the symptomatic treatment of OA knees over 32 weeks of therapy.

PMID- 17043521
TI  - Effects of functional electrostimulation on pain, muscular strength, and
      functional capacity in patients with osteoarthritis of the knee.
AB  - BACKGROUND: Osteoarthritis (OA) of the knee is a common cause of chronic
      disability in patients with quadriceps muscle weakness. Beneficial effects have
      been proposed for functional electrostimulation (FES) and exercise at the muscle
      level. OBJECTIVES: The objective of the study was to begin to compare the effects
      of both therapeutic modalities on quadriceps muscle strength, pain, and
      functional capacity in patients with OA of the knee and to prove whether the
      combination of these modalities provides greater benefits than the use of each
      therapeutic modality alone. METHODS: This pilot study included 37 patients with
      OA of the knee who were assessed at baseline and at 8 weeks, accounting for the
      following variables: body mass index, knee pain (measured using a VAS), WOMAC,
      quadriceps strength (measured using a dynamometer) and 6-minute walk test.
      Patients were randomized into 3 groups: (A) 8 patients who received FES 3 times
      per week; (B) 10 patients recruited into a twice-a-week physical training
      program; and (C) 8 patients under combined therapy; 29.7% of patients were lost
      to follow-up due to noncompliance with the treatment plan, leaving a total of 26
      patients at 8 weeks. RESULTS: Pain and WOMAC improved in all 3 groups; strength
      improved significantly in the exercise-only group; the FES + exercise combination
      improved strength significantly when compared with the individual therapeutic
      procedures. CONCLUSIONS: FES merits a larger placebo-controlled study as it may
      prove to be useful patients with OA of the knee; the combination with exercise
      was helpful in improving muscle strength. This technique may be considered in
      patients who are unable to carry out physical activity due to health problems or
      in those who are not interested in physical activity.

PMID- 17043522
TI  - Total joint fluid urate in gout.
AB  - BACKGROUND: Synovial fluid urates are traditionally measured as supernatants, and
      levels are reported to be comparable to serum levels. OBJECTIVE: We have decided
      to attempt to define a more accurate parameter of gouty urate load in the joint
      fluid. METHODS: In 23 gouty joints of various activity, the urate level was
      determined by both the traditional method and by heating and agitation to
      dissolve crystals yielding total joint fluid urate (TJFU). RESULTS: TJFU was
      higher than the serum level or traditional urate level, and the gradient (TJFU
      synovial fluid urate) was proportional to gouty activity. CONCLUSIONS: We propose
      that TJFU is more representative of the pathophysiology of gout and deserves
      further evaluation of its implications.

PMID- 17043523
TI  - Preoperative autologous blood donation by arthritis patients is associated with
      preoperative anemia and perioperative transfusion.
AB  - BACKGROUND: Preoperative autologous blood donation (PAD) became a common practice
      in the 1990s in an attempt to reduce the risk of transmission of infectious
      agents from allogeneic blood. However, a potential risk of PAD is the development
      of preoperative anemia that may lead, in turn, to an enhanced need for
      transfusion. Furthermore, the ready availability of autologous blood may
      predispose to more liberal transfusion peri-/postoperatively. OBJECTIVES: To
      examine these hypotheses, we retrospectively examined a cohort of knee and hip
      arthroplasty patients. METHODS: Charts of patients of 2 orthopedic surgeons from
      the mid 1980s and 1990s were reviewed for transfusions needed and hematocrits
      before and after arthroplasties. RESULTS: PAD proved to be a significant risk
      factor for the development of preoperative anemia and for peri-/postoperative
      blood transfusion even after adjusting for confounders. CONCLUSIONS: These
      results suggest that PAD may lead to a self-defeating cycle of blood donation
      followed by blood transfusion. With the improved safety of the allogeneic blood
      supply, rheumatologists may want to play a more active role in considering PAD in
      patients in whom elective arthroplasty is planned.

PMID- 17043524
TI  - Evidence-based soft tissue rheumatology. V: plantar talalgia.
AB  - Present evidence indicates that the main cause of plantar talalgia (PT) is a
      noninflammatory derangement at the proximal insertion of the plantar fascia. In
      athletes, predisposing ankle and rear-foot biomechanical abnormalities have been
      identified; in nonathletes, risk factors for the condition remain controversial.
      PT diagnosis is largely clinical, the key findings being pain and tenderness on
      the plantar aspect of the rear foot. Ultrasonography is a reliable confirmatory
      study in doubtful cases. Therapies in PT include nonsteroidal anti-inflammatory
      drugs, orthotic devices, night ankle dorsiflexion splints, physiotherapy, local
      glucocorticoid, and extracorporeal shockwave therapy. In recalcitrant cases,
      surgery may be offered. Of these therapies, only local glucocorticoid, as
      delivered by injection or iontophoresis, has shown short-term efficacy in
      controlled trials. The efficacy of ankle dorsiflexion splints and extracorporeal
      shockwave therapy is still controversial. Thus, important knowledge gaps remain
      on etiology, diagnosis, and treatment of PT.

PMID- 17043525
TI  - Vasculitis of the female genital tract.

PMID- 17043526
TI  - Cauda Equina Syndrome as a Clinical Presentation of Primary Angiitis of the
      Central Nervous System (PACNS).
AB  - Primary angiitis of the central nervous system (PACNS) is a form of vasculitis
      affecting the central nervous system (CNS) that is not associated with systemic
      disease or vasculitis outside the CNS. It is a rare disease with significant
      morbidity and mortality. Delay in diagnosis and treatment is common due to its
      nonspecific clinical symptoms and lack of efficient noninvasive diagnostic tests.
      The finding of vasculitis in the leptomeningeal and cortical biopsy sample has
      remained the gold standard for making the diagnosis of PACNS. We describe a
      patient whose clinical symptoms of cauda equina syndrome led to a nerve root
      biopsy that was consistent with PACNS despite prior extensive investigations
      including a brain biopsy. This report highlights the cauda equina syndrome as a
      clinical presentation of PACNS and emphasizes the need for awareness of this rare
      condition.

PMID- 17043527
TI  - Fracture complicating the bone marrow edema syndrome.
AB  - Bone marrow edema syndrome (BMES), also known as transient regional osteoporosis,
      is a rare and poorly understood disease process. We present a case of an elderly
      patient with the BMES who had a relapsing and remitting course complicated by a
      hip fracture which presented the unique and a previously unreported opportunity
      to examine the bony architecture pathologically. The patient responded well to
      calcitonin and bisphosphonate therapy after surgical repair of his fracture.This
      case highlights an underappreciated potential complication of BMES. Though not
      previously reported in the literature, BMES may be associated with active
      osteoporotic changes, with an infrequent risk of fracture that may be amenable to
      potential therapeutic interventions. Pathologically, BMES may represent a
      spectrum of disease consisting of an osteoclast-rich phase (transient regional
      osteoporosis phase) predisposing to fracture in addition to the more indolent
      osteoclast-poor phase with bone marrow edema more commonly associated with the
      disease. We hypothesize that it is the osteoclastic-rich phase which may benefit
      from early introduction of weight bearing activities, calcitonin,
      bisphosphonates, or parathyroid hormone. For example, bisphosphonates reduce bone
      resorption directly. Indirectly, bisphosphonates may also increase osteoblast
      differentiation and number and thus improve bone quality, an added benefit in the
      treatment of bone involved in the BMES, whether in the osteoclast-rich or
      osteoclast-poor phase.Further study should evaluate this osteoclastic-rich phase,
      which may be a transient pathologic phenomenon and which has not been described
      previously. Transient regional osteoporosis, therefore, may represent one point
      in the spectrum of the BMES. Hence, we would argue that BMES is a more accurate
      name for the full spectrum of this disease entity.

PMID- 17043529
TI  - Thomas Sydenham (1624-1689), on Scorbutical Rheumatism: 1717.

PMID- 17043528
TI  - Scleroderma renal crisis following widespread application of topical
      triamcinolone.
AB  - A 52-year-old patient with early diffuse scleroderma (Scl) developed scleroderma
      renal crisis (SRC) following exposure to topical steroid cream. She had applied a
      larger-than-prescribed quantity of triamcinolone acetonide 0.1% cream all over
      her body for 3 months, the absorption of the cream being the equivalent of 7.5 mg
      of oral prednisone per day. Her SRC was subsequently managed successfully with
      aggressive antihypertensive therapy and hemodialysis, and she was discharged
      home. High-dose corticosteroids (CS) have long been implicated in the development
      of SRC, but topical and low-dose CS until now have not. In our opinion, low-dose
      CS and a predisposing clinical setting appeared sufficient to provoke SRC and may
      broaden the proscription against CS in Scl.

PMID- 17043530
TI  - Basic science for the clinician 31: CD molecules of relevance to immunity,
      inflammation, and rheumatologic syndromes.
AB  - Molecular biologic technology has allowed us to study some of the many proteins
      expressed by leukocytes at different stages of differentiation, activation, and
      proliferation. Being able to purify cells with 1 or more surface molecules (eg,
      by FACS or lysis) with monoclonal antibodies and complement and identifying
      changes as cells are stimulated or activated has given us real insights into what
      is happening and how we might be able to modify cells that are going astray (eg,
      malignancy, autoimmunity). Over the years, there has been remarkable cooperation
      between laboratories to bring order out of chaos; by trading reagents, scientists
      have been able to identify the molecules being identified by different
      laboratories and come up with standardized names, often within the CD, or
      "clusters of differentiation," framework. These names are not acronyms, and the
      function and role of the molecule bearing a certain CD designation is not
      apparent. Worse, the proliferation of numbered CD molecules (over 250, with more
      to come after another conference in 2004) makes interpretation of the literature
      very difficult for those not immersed in the field. Thus, I have chosen (nearly
      arbitrarily and often based on my own interests) a number of CD molecules to
      briefly describe, pointing out the clinical relevance of each. It is worth
      reflecting on the fact that many of these were discussed in previous
      contributions to this series (as is pointed out in the following article). For
      those of you with the fortitude to follow this series, see how far you (and all
      of science) have come!

PMID- 17043531
TI  - Railway spine, posttraumatic fibromyalgia, and junk science in the courtroom (ca.
      1975).

PMID- 17043532
TI  - Failure to identify Salmonella bacteria DNA by polymerase chain reaction in
      peripheral blood and synovial fluid cells in chinese patients with rheumatoid
      arthritis and ankylosing spondylitis.

PMID- 17043533
TI  - Is primary biliary cirrhosis another example of an immune-mediated complication
      of klinefelter syndrome?

PMID- 17043534
TI  - Porphyria cutanea tarda and scleroderma.

PMID- 17043535
TI  - Lupus nephritis outcome with and without renal biopsy: a 5-year comparative
      study.
AB  - BACKGROUND: : Renal biopsy is an important tool in devising an adequate treatment
      plan for lupus nephritis. However, it is not always possible to perform a biopsy,
      and in many cases, treatment must rely exclusively on clinical data. OBJECTIVE: :
      The aim of this study was to compare the 5-year course of patients treated
      without a biopsy with another group with histologic evidence of diffuse
      proliferative glomerulonephritis (DPGN). METHODS: : The no-biopsy group consisted
      of 30 patients with lupus with strong clinical and laboratory suspicion of
      proliferative glomerulonephritis in whom a renal biopsy was unavailable either
      because of medical contraindication or the patient's refusal. The biopsy group
      included 30 patients undergoing biopsy and a histologic diagnosis of DPGN.
      Patients were followed from the onset of nephritis and at 18, 36, and 60 months.
      RESULTS: : At onset, the no-biopsy group showed lower C3 levels and higher
      proteinuria, although both groups showed evident deterioration of the renal
      function. No significant differences were found in treatment, outcome, survival,
      renal function tests, or in the development of kidney failure. CONCLUSIONS: :
      Proliferative glomerulonephritis deserves prompt diagnosis and treatment. This
      study demonstrates that experience in the management of lupus nephropathy,
      together with clinical and laboratory data, are often enough information to
      adequately treat proliferative glomerulonephritis even in the absence of a renal
      biopsy.

PMID- 17043536
TI  - Does transcutaneous electrical nerve stimulation improve the physical performance
      of people with knee osteoarthritis?
AB  - BACKGROUND: : According to a recent metaanalysis study, there is strong evidence
      to support the view that transcutaneous electrical nerve stimulation (TENS) is an
      effective treatment for managing osteoarthritis (OA) knee pain. However, there is
      limited evidence showing its effectiveness in improving physical function. This
      study examined whether TENS alone can improve physical function in terms of range
      of knee motion and the Timed-Up-and-Go Test. METHODS: : Subjects were randomly
      allocated into 2 groups receiving TENS at 100 Hz or a placebo TENS. Outcome
      measures included: 1) visual analog scale for measuring the intensity of the
      present pain, 2) Timed-Up-and-Go Test, and 3) range of knee motion (ROM).
      Repeated-measures analysis of variance and Pearson correlation were used for data
      analyses. RESULTS: : By day 10, TENS produced a significantly greater increase in
      maximum knee ROM than the placebo group (P = 0.033). TENS also significantly
      increased the pain-limited knee ROM across sessions, but the between-group
      difference was short of significance (P = 0.067). The decrease in time in
      performing the Timed-Up-and-Go Test was also not significantly different between
      the 2 groups. A moderate correlation was observed between the reduction in pain
      scores and the improvement in the Timed-Up-and-Go Test. CONCLUSIONS: : Our
      findings suggested that TENS did improve some of the physical parameters but over
      10 days was unable to produce significant improvement in functional performance
      among people with knee OA. A larger-scale study with the assessment of other
      functional outcomes may be required to clarify if TENS could improve function in
      people with knee OA. Also, exercise can be considered to be an important adjunct
      treatment to TENS to improve function significantly.

PMID- 17043537
TI  - Brucellar spondylitis: review of 25 cases.
AB  - OBJECTIVE: : Brucellar spondylitis is one of the most serious complications of
      brucellosis. It should be considered in patients who have back pain and
      neurologic disorders as well as systemic symptoms and findings in or from endemic
      areas such as Turkey. This report describes important features of the disease.
      METHODS: : Twenty-five patients with brucellar spondylitis were retrospectively
      evaluated in terms of their clinical, laboratory, and radiologic features and
      their response to different treatment regimens. RESULTS: : The most common
      symptoms of brucellar spondylitis were back pain, fever, and sweating. Rose
      Bengal tests were positive in all of these patients. Brucella species was
      isolated from blood cultures of 8 (32%) patients. Magnetic resonance imaging
      (MRI) showed that the lumbar segment was the most frequently involved region.
      Different combination regimens including 2 or 3 antibiotics were used.
      Combination of tetracycline (especially doxycycline) and streptomycin was the
      most widely used therapy regimen. Trimethoprim-sulfamethoxazole, ciprofloxacin,
      ofloxacin, and rifampin were also included in some combination therapies. In this
      series, the mean duration of antimicrobial therapy was 130 +/- 45.6 days (range,
      77-281 days), and 92% of patients received therapy for >/= 90 days. There were no
      mortalities in this study. CONCLUSIONS: : Brucellar spondylitis should be
      considered in patients with back pain and neurologic disorders as well as
      systemic symptoms and findings in endemic areas. MR imaging is recommended in
      suspected cases. The patients can be treated effectively treated with appropriate
      antibiotic combinations. Follow up is important because relapses can occur.

PMID- 17043538
TI  - Prevalence of comorbid conditions and prescription medication use among patients
      with gout and hyperuricemia in a managed care setting.
AB  - BACKGROUND: : Comorbid disorders and multiple prescription drug use are common
      among patients with gout and/or hyperuricemia and may influence the clinical
      course and outcome of gout. OBJECTIVE: : We wanted to document the conditions and
      associated medications in a large group of patients with gout in a managed care
      setting. METHODS: : This study was a 2-year, retrospective, administrative claims
      analysis examining comorbid conditions and medication use among managed care
      enrollees with gout/hyperuricemia across the United States. RESULTS: : Of the
      9482 study subjects (82.1% men, mean age 52 years), 57.9% had hypertension, 45.3%
      had a lipid disorder, 32.5% had both conditions, and 19.9% had diabetes mellitus.
      During the 24-month follow-up period, subjects had 5 +/- 3.14 (mean +/- standard
      deviation) different comorbid conditions and filled prescriptions for of 11.0 +/-
      7.90 different medications. The most commonly filled prescriptions included
      antihypertensive drugs, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors (statins), and nonsteroidal antiinflammatory drugs (NSAIDs).
      CONCLUSIONS: : The study indicates a high prevalence of both comorbid conditions
      and multiple medication use among managed care enrollees with gout and/or
      hyperuricemia. Heightened awareness of these associated disorders is important
      because they may warrant treatment of their own accord and often some
      modification of gout management. Drugs, particularly diuretics and prophylactic
      aspirin, could potentially contribute to the development of hyperuricemia and
      gout.

PMID- 17043539
TI  - Can a nurse-directed intervention reduce the exposure of patients with knee
      osteoarthritis to nonsteroidal antiinflammatory drugs?
AB  - OBJECTIVE: : The objective of this study was to evaluate a nurse-directed self
      management intervention for managed care patients with knee osteoarthritis (OA),
      emphasizing nonpharmacologic (NonPharm) management of pain and functional
      impairments and minimization of exposure to the risks and costs of nonsteroidal
      antiinflammatory drugs (NSAIDs). METHODS: : Subjects were 186 patients from a
      large health maintenance organization (HMO) who satisfied American College of
      Rheumatology clinical criteria for knee OA. Two of 4 HMO sites (and their patient
      cohorts) were randomly assigned to the education group; the other 2 served as a
      delayed-intervention control group. At each location of care for the education
      group, an arthritis nurse educator, in consultation with the patient's primary
      care physician (PCP), followed a detailed algorithm for implementing and
      monitoring the response to NonPharm treatment modalities (eg, quadriceps
      strengthening exercises, counseling in principles of joint protection, use of
      thermal modalities). The nurses apprised the PCP of the patient's progress and
      made algorithm-based recommendations, as appropriate, for reduction of dose, and
      eventual discontinuation, of NSAIDs in favor of acetaminophen. Outcomes (measured
      at baseline, 3, 6, and 12 months) included pain and function scales from the
      Western Ontario and McMaster Universities (WOMAC) OA Index. RESULTS: : The
      treatment groups were similar at baseline with respect to sociodemographic and
      clinical characteristics. Medical record audits revealed that NonPharm treatments
      (most often exercise) were implemented by 75% of patients in the education group
      but by only 18% of patients receiving routine care (P < 0.00001). Over the
      subsequent 12 months, 20 patients (26%) in the education group, but only 3 (5%)
      in the control group (P = 0.002), underwent changes in drug treatment of OA pain
      consistent with the NSAID-sparing goals of the intervention, ie, acetaminophen as
      initial drug of choice; reduction in dose, or discontinuation, of NSAID; switch
      from an NSAID to an analgesic. Only one patient in the education group required
      reinstitution of NSAIDs because of an increase in knee pain. Mean WOMAC scores
      indicated no deterioration of pain control or function over 12 months in the
      group treated according to the algorithm. CONCLUSION: : Incorporation into the
      primary care setting of self-care education for patients with knee OA, with
      collaboration between a proactive arthritis nurse and the patient's PCP, can
      reduce reliance on NSAIDs without a resultant increase in OA pain and disability.

PMID- 17043540
TI  - The prevalence of fibromyalgia in collegiate athletes.
AB  - BACKGROUND: : The prevalence of fibromyalgia in the general population is
      reported in numbers that range between 0.5% and 10%, with considerable
      variability in the populations studied and criteria for diagnosis used. The
      prevalence in competitive young adult athletes is unknown, but we expect it to be
      less than the general population. OBJECTIVES: : The objective of this study was
      to determine the prevalence of fibromyalgia in college student athletes. METHODS:
      : We conducted a prospective, cross-section cohort evaluation of 641 athletes
      using the 1990 American College of Rheumatology (ACR) criteria. Volunteer college
      student athletes were evaluated with a questionnaire and physical examination at
      preparticipation physical examinations from 1993 to 1999. RESULTS: : Of the 641
      athletes examined, we found only one who met the ACR criteria for a diagnosis of
      fibromyalgia. LIMITATIONS: : There were a limited number of athletes involved,
      there was no age- or activity-matched control group, and there were no other
      demographic information or associated symptoms collected. CONCLUSIONS: : The
      prevalence for fibromyalgia in this population was found to be 0.16%, which is
      lower than the prevalence found in studies describing other populations. The
      protective effects of this population are unclear but could be related to age,
      fitness level, self-selection, and/or other factors.

PMID- 17043541
TI  - Corticosteroid therapy in an alphaviral arthritis.
AB  - BACKGROUND: : Corticosteroid use during acute viral arthritis is considered to be
      contraindicated as a result of the risk of immunosuppression causing enhanced
      infection and disease exacerbation. OBJECTIVES: : The objective of this study was
      to analyze the effect of oral corticosteroid therapy on symptoms of the viral
      arthritic disease, Ross River virus disease (RRVD). METHODS: : Patients with RRVD
      were enrolled in 2 prospective longitudinal studies. Medications and
      comorbidities were recorded and the patients' health was assessed using 2
      validated quality-of life-questionnaires, the Comparison of Clinical Health
      Assessment Questionnaire (CLINHAQ) and the Medical Outcomes Study Short Form (SF
      36). RESULTS: : Six patients taking corticosteroids showed no exacerbation of
      RRVD compared with patients not taking steroids. The CLINHAQ Functional
      Disability Index also indicated that corticosteroid users recovered faster
      compared with patients using nonsteroidal antiinflammatory drugs. CONCLUSION: :
      Conventional concern that corticosteroid treatment will exacerbate disease
      appears unjustified for alphaviral arthritides once serodiagnosis has
      demonstrated antiviral immunity.

PMID- 17043542
TI  - Refractory sweet syndrome with autoimmune organizing pneumonia treated with
      monoclonal antibodies to tumor necrosis factor.
AB  - We describe a 54-year-old man with highly refractory Sweet syndrome associated
      with autoimmune multifocal organizing pneumonia and underlying myelodysplastic
      disorder. His lung disease responded to oral cyclophosphamide. However, his skin
      disease and systemic symptoms followed a chronic course and responded only to
      very high doses of corticosteroid and were refractory to a number of
      corticosteroid-sparing agents. He was ultimately treated with infliximab,
      resulting in remission of his cutaneous and systemic symptoms and successful
      tapering of his corticosteroid dose. Subsequently, infliximab was replaced with
      adalimumab to achieve more sustained remission. His pulmonary lesions have not
      recurred on this treatment. His myelodysplastic syndrome followed a very slowly
      progressive course consistent with refractory anemia. This case report
      demonstrates the effectiveness of treatment with monoclonal antibody specific for
      tumor necrosis factor alpha (TNFalpha) in a patient with severe manifestations of
      Sweet syndrome refractory to other treatments.

PMID- 17043543
TI  - Accelerated cutaneous nodulosis during infliximab therapy in a patient with
      rheumatoid arthritis.
AB  - Up to one fourth of patients with rheumatoid arthritis (RA) may have
      extraarticular findings such as subcutaneous nodules. These are discrete
      subcutaneous granulomatous nodules located on extensor surfaces, especially of
      the elbows. Over the past 10 to 15 years, there have been reports of accelerated
      cutaneous nodulosis in patients receiving methotrexate therapy. Recently,
      antitumor necrosis factor alpha (anti-TNFalpha) biologic therapy has become
      commonplace in the management of RA, especially in methotrexate-resistant or
      toxic patients. There have been recent reports of accelerated nodulosis in
      patients with RA on etanercept. We describe what we believe is the first case of
      accelerated cutaneous nodulosis resulting from infliximab anti-TNFalpha therapy
      in a patient with RA. One year after the initiation of infliximab, with RA in
      remission, our patient noted the rapid development of rheumatoid nodules of both
      hands. A biopsy was characteristic of a rheumatoid nodule, revealing palisading
      granulomas and fibrinoid necrosis.

PMID- 17043544
TI  - Hashimoto encephalopathy (autoimmune encephalitis).
AB  - Patients with Hashimoto thyroiditis may have neurologic manifestations that have
      been described in the literature for some decades now; these include psychiatric
      disorders, abnormal movements, and simulation of cerebrovascular events. Nuclear
      magnetic resonance (MRI) studies have revealed diffuse leukoencephalopathy in
      most cases. We describe a case having clinical manifestations simulating
      cerebrovascular events, together with cognitive alterations (a presentation
      already described in other patients). Among the 2 main forms of neurologic
      manifestations, the cognitive type, which is probably associated with
      endocrinologic alteration, may improve with hormone supplement. Those alterations
      simulating cerebrovascular events are most probably related to autoimmune
      vasculitis. The latter may improve with the administration of corticosteroids,
      which are proposed as treatment of this disorder.

PMID- 17043545
TI  - Comment.

PMID- 17043546
TI  - Combination therapy with montelukast and ketotifen for arthritis and rash
      resulting from idiopathic hypereosinophilic syndrome.
AB  - Idiopathic hypereosinophilic syndrome (IHES) is a rare condition of uncertain
      etiology characterized by marked peripheral blood eosinophilia and organ system
      dysfunction that cannot be explained by any factor other than the presence of
      eosinophils or their potentially toxic products. Diagnostic criteria include 1) a
      sustained eosinophilia greater than 1500/mm for longer than 6 months, 2) absence
      of other causes of eosinophilia, including parasitic infections and allergic
      diseases, and 3) multiorgan involvement (ie, lungs, heart, central nervous
      system, skin, liver, joints). Steroids represent the initial therapeutic
      approach, although for those patients unresponsive to steroids, cytotoxic
      chemotherapy should be considered. We describe a case of IHES characterized by
      polyarticular inflammatory joint involvement, hypereosinophilia, and urticarioid
      skin manifestations without visceral involvement. Synovial fluid smears as well
      as pathology of skin lesions and knee synovial membrane confirmed the presence of
      numerous eosinophils. The patient was successfully treated with a combination
      therapy of a cysteinyl leukotriene receptor antagonist (montelukast) and
      ketotifen. Hypereosinophilic syndrome like in this patient is a rare cause of
      polyarthritis.

PMID- 17043547
TI  - Rheumatology grand rounds at rush: patient self-report data are key to better
      patient care.

PMID- 17043548
TI  - Jean martin charcot (1825-1893), on gout.

PMID- 17043549
TI  - Crossword puzzle.

PMID- 17043550
TI  - Basic science for the clinician 33: interleukins of current clinical relevance
      (part I).
AB  - Normal orchestration of wound healing, the protective immune response and
      inflammation, involve a bewildering array of cells that communicate to each other
      locally by means of cell-surface receptors and their ligands. For local and
      middle- to long-distance coordination, some of these same cells make and export
      soluble messengers that communicate to both immune and nonimmune cells. Although
      all these messengers have a role in normal immune homeostasis, it is apparent
      that many are involved in tissue damage in a variety of diseases, eg, rheumatoid
      arthritis and osteoarthritis. Some of these molecules are known as interleukins.
      The list of interleukins (IL) is now nearing 30 and, as a result of the molecular
      biology revolution, we now know the direct clinical relevance of many of them. As
      benchtop molecular biology matures into therapeutic and diagnostic tools,
      clinicians must begin to master this disparate group of molecules; making this
      harder is the fact that unlike acronyms (often impenetrable as they might be), an
      IL designation does not give a clue as to the source, target, or action of the
      IL. IL-1 and IL-2 were the first messengers to bear the "interleukin" name 25
      years ago; they are well known to rheumatologists by now, so this article deals
      with some of the characteristics of the other clinically relevant IL molecules
      starting with IL-3.

PMID- 17043552
TI  - The end of an era: a commentary on the demise of the bulletin on rheumatic
      diseases (1950-2004).

PMID- 17043551
TI  - Small joint monoarthritis and pyoderma gangrenosum in newly diagnosed ulcerative
      colitis: an unusual presentation.

PMID- 17043553
TI  - Avoiding all nonsteroidal antiinflammatory drug toxicity.

PMID- 17043555
TI  - The association of smoking with vaginal flora, urinary tract infection, pelvic
      floor prolapse, and post-void residual volumes.
AB  - OBJECTIVE: This study examined the association of smoking with changes in vaginal
      flora, the prevalence of urinary tract infection, genital prolapse, and
      incomplete bladder emptying. METHODS: The authors conducted a retrospective
      review of charts for 305 women. In addition to smoking habits, data on age,
      parity, degree of genital prolapse, vaginal flora, urinary residual, urinary
      tract infection, and hormone replacement therapy were collected and analyzed.
      RESULTS: Smoking did not correlate with urinary tract infection, the amount of
      post-void urine residual volumes, or pessary use. Smoking was significantly
      associated with the presence of a severe degree of genital prolapse. Smoking
      independently affected vaginal flora, increasing the odds of developing bacterial
      vaginosis. CONCLUSION: Smoking was associated with an increased risk of
      developing bacterial vaginosis and having severe genital prolapse. Smoking was
      not associated with urinary tract infection or the amount of post-void residual
      urine.

PMID- 17043554
TI  - Endocervical sampling: a comparison of endocervical brush, endocervical curette,
      and combined brush with curette techniques.
AB  - OBJECTIVE: This study was conducted to compare the collection of endocervical
      specimens by endocervical brush, curette, and a combined curette and brush
      technique. METHODS: Women underwent colposcopy with endocervical curettage using
      one of 3 collection methods. RESULTS: The endocervical brush produced equivalent
      amounts of tissue and endocervical cells compared to the curette alone or
      combined techniques. More squamous and glandular atypia and SIL/AIS were found
      when a brush was used, but a statistically significant difference was not noted.
      The brush alone produced a significantly greater percentage of samples that were
      insufficient for diagnosis and more specimens without stromal components. The
      brush with the curette as a combined technique provided no improvement in amounts
      of tissue, endocervical cells/clusters, or amount of stroma retrieved.
      CONCLUSION: Each technique has advantages and disadvantages in terms of what
      types of components are collected and what diagnosis may be determined from the
      sample taken.

PMID- 17043556
TI  - Genital human papillomavirus types in immunocompetent and immunodepressed women
      in northeast Italy: prevalence and cytomorphological correlations.
AB  - OBJECTIVE: We evaluated the prevalence of genital human papillomavirus (HPV)
      types in correlation with cytomorphological findings in patients at different
      risk for cervical intraepithelial neoplasia living in northeast Italy. METHODS:
      Exfoliated cervicovaginal cells from 943 women, who were divided into three
      groups, were analyzed by polymerase chain reaction. RESULTS: Overall, HPV
      prevalence rates were 7%, 38%, and 52%, respectively. The single most frequent
      type was HPV 16 (18%), followed by types 6, 31, 53, 58, 61, and
      novel/unidentified (5-7%); other types had a frequency <5%. Infection with
      multiple types was present in 12%. In HIV-infected women, HPV infection was
      correlated with lower CD4 level and higher viral load; HGSILs were correlated
      only with a lower CD4 count, and no correlations were found for LGSILs.
      CONCLUSIONS: HGSILs were associated with high-risk types, mainly HPV 16 (40%).
      LGSILs, instead, were associated with a broad spectrum of low-risk and high-risk
      types.

PMID- 17043557
TI  - Cervical cytology and other screening methods among women admitted to the medical
      intensive care unit.
AB  - OBJECTIVE: This study was conducted to determine whether routine gynecologic
      screening is obtained for women admitted to a medical intensive care unit in a
      large tertiary medical center and whether this history is used to document and
      update screening for these patients. METHODS: A retrospective chart review of 65
      women admitted to the medical intensive care units of Harper Hospital or Detroit
      Receiving Hospital of the Detroit Medical Center over a period of one month.
      RESULTS: None of the patients eligible for cervical cytology and pelvic
      examination had these issues addressed in the intake history or had any of the
      reviewed examinations done or planned for after discharge from intensive care.
      CONCLUSIONS: Admission to intensive care is an opportunity to assess and update
      routine gynecologic health screening. This important function is not routinely
      addressed in the medical records of women admitted to intensive care.

PMID- 17043558
TI  - Cervical cancer screening in Porto Alegre, Brazil: alternative methods for
      detecting cancer precursors in a developing country.
AB  - OBJECTIVE: This study was conducted to test the performance characteristics of
      cervical cancer screening by visual inspection of the cervix with acetic acid and
      iodine solution. METHODS: A total of 100 women were screened for cervical cancer
      by Pap smear and naked eye inspection of the cervix after application of acetic
      acid and iodine solution. RESULTS: Comparing visual inspection to the Pap test, a
      sensitivity of 85.7%, specificity of 78.5%, and concordance of 79% (p < .0011)
      was established. Comparing the Pap test with colposcopy, the corresponding
      figures were 42.9%, 92.3%, and 66.6% (p < .077), respectively. Visual inspection
      compared to colposcopy showed corresponding figures of 100%, 7.7%, and 55.5% (p =
      .48), respectively. Colposcopy and biopsy had an agreement of 100%. CONCLUSIONS:
      Visual inspection with acetic acid and iodine solution proved to be a reasonable
      method of screening for cervical cancer precursors.

PMID- 17043559
TI  - Human papillomavirus testing for triage in a referral population.
AB  - OBJECTIVE: This study evaluated the Digene HPV Assay Hybrid Capture System(R) as
      a triage method. METHODS: Results of an HPV assay were compared with a final
      tissue diagnosis of cervical intraepithelial neoplasia 2 (CIN2) or greater. These
      results were stratified based on Pap smear diagnosis and evaluated in 4 triage
      algorithms. RESULTS: Of the 4 algorithms evaluated, the highest savings came from
      not performing colposcopy for patients with repeat atypical squamous cells of
      undetermined significance (ASCUS), but that resulted in missing nine patients
      with CIN2 and CIN3 histology. HPV testing failed to diagnose 67% (6 out of 9) to
      48% (10 out of 21) of patients with underlying CIN2 and CIN3. CONCLUSIONS:
      Although HPV high-risk positive results correlate with high-grade histology, it
      is associated with significant false negatives. The HPV low-risk test is not
      clinically useful. These tests were poor methods to triage patients in our
      population.

PMID- 17043560
TI  - Treatment of cervical intraepithelial neoplasia levels 2 and 3 with adapalene, a
      retinoid-related molecule.
AB  - OBJECTIVES: This study examined dose scheduling, safety, and efficacy of
      adapalene in the treatment of CIN2 and CIN3. METHODS: Patients were instructed on
      insertion and removal of an adapalene delivery system. Treatment regimens of 4,
      8, and 14 days were utilized. Biopsies were performed on day 90 to assess
      efficacy. Safety was evaluated with toxicity questionnaires and patient
      interviews. RESULTS: Two patients treated for 4 days had stable disease. Twenty
      three patients treated for 8 days demonstrated an overall 61% (14 of 23) response
      rate. Twenty-four patients treated for 14 days had an overall 38% (9 of 24)
      response rate. No patient had disease progression. Compared to untreated
      historical controls, significantly improved efficacy was demonstrated for
      patients with CIN2. Patients with CIN3 had improved efficacy, though not
      statistically significant. CONCLUSIONS: The lack of side effects and practicality
      of home use make adapalene a nontoxic and safe alternative to surgical therapy in
      patients with CIN2 and CIN3.

PMID- 17043561
TI  - Testicular torsion: a review.
AB  - Torsion of the testis, also referred to as torsion of the spermatic cord, is a
      subject of debate among physicians and surgeons. Testicular torsion is an acute
      vascular event causing the rotation of the vascular pedicle of the testis,
      thereby impeding the blood flow to the testis and the scrotal contents. It could
      be either within or outside the tunica vaginalis. Testicular torsion causes
      immediate circulatory changes and long-term sequelae such as testicular function
      and fertility. It is considered a surgical emergency, as a delay causes
      irreversible testicular damage. The diagnosis and treatment of testicular torsion
      are discussed in this review, which also illustrates an algorithm and a scoring
      system for the diagnosis and management of this condition based on current
      literature.

PMID- 17043562
TI  - Asymptomatic lung carcinoma presenting with a large vulvar lesion.
AB  - OBJECTIVE: Metastases to the vulva are infrequent, accounting for less than 10%
      of vulvar tumors. Vulvar metastases from lung carcinoma have been reported in two
      other cases. METHODS: A case of lung carcinoma metastatic to the vulva is
      reported. RESULTS: A 71-year-old woman was referred to The University of Iowa
      Hospitals and Clinics with a lung nodule on chest x-ray and a 12-cm, necrotic,
      left vulvar mass. A lung biopsy showed poorly differentiated carcinoma, and a
      palliative resection of the vulvar mass showed metastatic lung carcinoma. The
      patient died from sepsis on postoperative day 10. CONCLUSIONS: Lung carcinoma
      metastatic to the vulva is rare and portends a poor prognosis.

PMID- 17043563
TI  - Home study course: winter 2001.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 17043564
TI  - American Society for Colposcopy and Cervical Pathology.

PMID- 17043577
TI  - How should a patient with a series of mildly abnormal Pap smears be managed?

PMID- 17043578
TI  - Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical
      neoplasia.
AB  - OBJECTIVE: To determine the ability of Multimodal Hyperspectral Imaging (MHI) to
      noninvasively detect, localize and diagnose cervical neoplasia. MATERIALS AND
      METHODS: The cervical epithelium was interrogated by MHI using tissue
      fluorescence and reflectance measurements after the probe was placed on the
      ectocervix. A Papanicolaou smear was taken, and a colposcopic examination was
      performed and cervical histologic specimens were collected, when indicated. MHI
      and Pap smear sensitivity and specificity data were compared with colposcopic and
      histologic results. RESULTS: Nineteen patients had CIN2 or higher, 30 had CIN1,
      34 had benign cellular changes or metaplasia, and 28 were normal by both Pap
      smear and colposcopic examination. At equal specificity (70%) for both tests, the
      sensitivity of MHI was 97%, compared to 72% for the Pap smear. CONCLUSION: MHI
      detected cervical cancer precursors at a rate greater than that obtained by a
      simultaneously collected Pap smear.

PMID- 17043579
TI  - Reporting the potential benefits of new technologies for cervical cancer
      screening.
AB  - The AHCPR released its evidence-based report, "Evaluation of Cervical Cytology"
      in early 1999. This report represents the most comprehensive analysis available
      to date of Pap smears and new technologies designed to improve cervical cancer
      screening. Both the ACOG and the AHCPR have released simplified summaries of the
      results of the evidence report that may lead to misunderstandings of the
      potential clinical impact of these new technologies. This report reviews the 4
      major statements in these summaries and discusses how they are either incorrect
      based on the full AHCPR report or may be misinterpreted because their
      ramifications are not fully discussed. New screening technology has the potential
      to finally bring the sensitivity of a new Pap test to an acceptable level. The
      increased sensitivity afforded by these new technologies can reduce negative
      outcomes at reasonable cost-effectiveness ratios and at an equivalent or superior
      specificity compared to the conventional Pap smear.

PMID- 17043580
TI  - Efficacy of treatment of inflammatory cytologic abnormalities detected by
      papanicolaou smears: a pilot study.
AB  - OBJECTIVE: To evaluate the efficacy of metronidazole versus no treatment for the
      empiric treatment of inflammatory cytologic changes. MATERIALS AND METHODS:
      Patients with inflammatory changes on Pap smear were serially assigned to receive
      no treatment or metronidazole by one of three regimens: 2 grams orally as a
      single dose, 500 milligrams orally twice daily for 7 days, or 5 grams (in gel
      form) vaginally twice daily for 5 days. Smears were repeated 3 months after
      treatment. RESULTS: The repeat smear was normal in 47 of 63 patients treated with
      a single dose, 40 of 62 patients treated orally for 7 days, 14 of 21 patients
      treated with vaginal gel, and 29 of 49 of the control group. Chi-square analysis
      showed no statistical significance between groups. CONCLUSION: There is no
      statistically significant difference in the resolution of cytologic inflammatory
      changes among the study groups. Empiric metronidazole treatment has no benefit.

PMID- 17043581
TI  - Continous flow vaginoscopy in children.
AB  - The inspection of the vagina may be necessary in childhood whenever abnormal
      bleeding or persistent vulvovaginitis occurs. The intact and narrow laryngeal
      ring is a significant obstacle to the physician. Continuous-flow vaginoscopy
      using the hysteroscope and normal saline for irrigation and distention is very
      quick, easy and efficacious. Procedures, such as hemostasis, biopsy or foreign
      body removal can be performed during its application.

PMID- 17043582
TI  - Evaluation of the sexually abused child, including the role of colposcopy.
AB  - The magnification and excellent lighting provided by the colposcope make it an
      excellent diagnostic tool when enhanced direct observation is required. What can
      be accomplished with this tool in a pediatric or adolescent patient depends upon
      the examiner understanding how to best perform the examination related to these
      age groups and knowing what they see. This article describes common techniques
      used in the examination of the young gynecologic patient and common normal and
      abnormal findings. This knowledge should be especially helpful to the
      practitioner who is called upon to perform a sexual abuse examination in this
      population.

PMID- 17043583
TI  - Adenocarcinoma in situ of the cervix-controversies in diagnosis and treatment.
AB  - Adenocarcinoma in situ (AIS) of the uterine cervix is a rare condition. Pap smear
      screening is unsatisfactory, and the disease has no morphologic reliable
      colposcopic features. Diagnosis is often made by chance during the treatment of
      squamous pre-invasive disease, which commonly coexists with AIS. Although the
      entire endocervical canal can be the site of disease, most lesions lie within 1
      cm of the squamocolumnar junction. Skip lesions are rare, making fertility
      sparing surgery a possibility under certain conditions. Recurrent disease occurs
      in 14% of cases when cone margins are free of disease and rise to more than 50%
      if the margins are involved. The method of conization is immaterial provided a
      large enough specimen is taken and that the endocervical margins can be evaluated
      by the pathologist. Follow-up of conservatively managed women is not defined;
      however, we recommend that regular endocervical cytology be performed in addition
      to conventional cytology and colposcopy.

PMID- 17043584
TI  - Condoms or abstinence for one year then retest for hpv?

PMID- 17043585
TI  - How should a patient with a series of abnormal pap smears be managed?

PMID- 17043587
TI  - The american society for colposcopy and cervical pathology: hagerstown, MD.

PMID- 17043586
TI  - Home study course: spring 2001.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category 1 of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 17043589
TI  - Conservative management of adenocarcinoma in situ of the cervix.

PMID- 17043588
TI  - Significance of Atypical Squamous Cells of Undetermined Significance on ThinPrep
      Papanicolaou Smears.

PMID- 17043590
TI  - The natural history of cervical cryosurgical healing. The minimal effect of
      debridement of the cervical eschar.

PMID- 17043591
TI  - Presence of human papillomavirus and epstein-barr virus in the cervix of women
      infected with the human immunodeficiency virus.

PMID- 17043592
TI  - Papanicolaou smear history and diagnosis of invasive cervical carcinoma among
      members of a large prepaid health plan.

PMID- 17043593
TI  - Accuracy of patients' recall of pap and cholesterol screening.

PMID- 17043594
TI  - Healing experiences after cervical cryosurgery.

PMID- 17043595
TI  - Wet smear compared with gram stain diagnosis of bacterial vaginosis in
      asymptomatic pregnant women.

PMID- 17043596
TI  - Mandated coverage for cancer-screening services: whose guidelines do States
      follow?

PMID- 17043597
TI  - Knowledge about human papillomavirus among adolescents.

PMID- 17043598
TI  - Setting the target for a better cervical screening test: characteristics of a
      cost-effective test for cervical neoplasia screening.

PMID- 17043599
TI  - Validity of adolescent and young adult self-report of papanicolaou smear results.

PMID- 17043600
TI  - Cervical shedding of herpes simplex virus and cytomegalovirus throughout the
      menstrual cycle in women infected with human immunodeficiency virus type 1.

PMID- 17043601
TI  - Epithelial cell layer thickness and immune cell populations in the normal human
      vagina at different stages of the menstrual cycle.

PMID- 17043602
TI  - Risk factors for cervical stenosis after loop electrocautery excision procedure.

PMID- 17043603
TI  - Clinical evidence: issue 3, june 2000.

PMID- 17043604
TI  - Letters to the editor.

PMID- 17043605
TI  - Letters to the editor.

PMID- 17043606
TI  - Towards a tailor made treatment of thoraco-abdominal aneurysms!

PMID- 17043607
TI  - Endovascular treatment of thoracoabdominal aortic aneurysms.
AB  - Open surgical repair of thoracoabdominal aortic aneurysms (TAAA) bridges the
      aneurysm with a large, conventional, unstented graft and restores flow to the
      visceral arteries through short grafts or direct sutured connections between the
      visceral arterial orifices and the primary conduit. The combination of retrograde
      visceral bypass and endovascular aneurysm exclusion substitutes an endovascular
      stent-graft for a standard graft, stented overlaps for sutured anastomoses, and
      transluminal insertion for direct aortic exposure. Compared to open surgery, the
      combination treatment requires less dissection, and causes less hemodynamic
      instability, and lower complication rates, particularly paraplegia. The multi
      branched stent-graft substitutes endovascular visceral bypass through branches of
      the stent-graft for surgical visceral bypass through branches of a conventional
      extraluminal graft, which has the potential to further reduce surgical
      dissection, hemodynamic instability, and complication rates. We favor a modular
      approach in which short, axially oriented cuffs are extended into the visceral
      arteries, using self-expanding covered stents. In the past year, we have used
      this approach to implant multi-branched thoracoabdominal stent-graft in 16
      patients. In our opinion, this approach will eventually assume a prominent role
      in the management of TAAA.

PMID- 17043608
TI  - Impact of the calf perforators on the venous hemodynamics in primary varicose
      veins.
AB  - The hemodynamic significance of the calf perforating veins continues to be the
      point of controversy. The conception that incompetent perforating veins cause
      hemodynamic disturbance and are responsible for the formation of leg ulceration
      has still many adherents prefering perforator surgery, whereas others reject any
      causal relation between large, incompetent perforators and severe forms of
      chronic venous insufficiency. In this study well documented facts concerning the
      impact of the calf perforators on the venous hemodynamics are reviewed. There is
      a bidirectional flow within calf perforators in healthy subjects enabling a quick
      equilibration of pressure changes produced during calf muscle contractions and
      relaxations, so that recordings of the mean pressure display identical values in
      superficial and deep veins of the lower leg, a feature typical of conjoined
      vessels. In cases with saphenous reflux, the bidirectional flow within calf
      perforators has a distinct inward vector directed to the deep veins; this inward
      component is the more pronounced, the larger the saphenous reflux is. Incompetent
      calf perforators do not cause ambulatory venous hypertension, exactly the
      opposite happens: the high hydrostatic pressure found in the quiet standing
      position drops significantly during ambulation, as soon as the saphenous reflux
      is interrupted. In primary varicose veins calf perforators can not become the
      source of reflux because they are situated at the lower pole of the ambulatory
      pressure gradient, which occurs between thigh and lower leg veins during
      ambulation. The size of the calf perforators is determined by the amount of
      saphenous reflux. When the saphenous reflux is abolished (e.g. by high ligation),
      the enlarged calf perforators diminish.

PMID- 17043609
TI  - Abdominal aortic aneurysm surgery: retroperitoneal or transperitoneal approach?
AB  - AIM: Mortality and morbidity of abdominal aortic aneurysm surgery have decreased
      significantly in time and transperitoneal approach (TPA) still preserves its
      popularity although retroperitoneal approach (RPA) is known to cause lower
      incidence and shortened duration of ileus, shorter intensive care unit (ICU) and
      hospital stay, earlier oral intake and less patient discomfort or pain. METHODS:
      One hundred and fifty patients that underwent abdominal aortic aneurysm repair at
      our Cardiovascular Surgery Center between January, 1990 and March, 2000 were
      reviewed and analyzed based on the elective/emergent nature of the surgery and
      the type of the incision as either TPA or RPA. RESULTS: Significantly shorter
      mechanical ventilation (15.2+/-3.8 vs 10.1+/-2.3 hours) and nasogastric
      decompression periods (40.6+/-10.7 vs 9.1+/-2.2 hours), less need for intravenous
      fluid supplementation and shorter ICU stay (29.5+/-14.8 vs 18.6+/-1.9 hours) were
      observed with the retroperitoneal approach (P<0.001). Need for allogeneic blood
      transfusion was, similar (1.3+/-1.4 vs0.9+/-0.4, P>0.05). Analysis of mortality
      and morbidity revealed bleeding as the major cause of mortality for ruptured
      aneurysm. A similar comparison between TPA and RPA groups, however, revealed no
      significant difference (P>0.05). CONCLUSIONS: | Retroperitoneal approach is a
      reliable technique causing less fluid-electrolyte imbalance with rapid
      restoration of gastrointestinal physiology. It causes less discomfort to patients
      with reduced need for analgesia. A shorter weaning period from mechanical
      ventilation is among the benefits for patients with co-morbid states.

PMID- 17043610
TI  - Surgical treatment of abdominal aortic aneurysm with concomitant renal cell
      carcinoma: a single-centre experience with review of the literature.
AB  - AIM: The association between abdominal aortic aneurysm (AAA) and renal cancer is
      becoming more frequent, raising several questions about therapeutic and surgical
      strategies of management for both diseases. METHODS: Between October 1988 and May
      2004, 913 AAA patients underwent surgical or endovascular repair at the I
      Division of General Surgery of the University of Verona (Italy). In 61 cases
      (6.7%) an association with a solid neoplasm was found; in 12 cases (1.3%) the
      neoplasm was a renal cell carcinoma. RESULTS: Ten patients underwent a
      simultaneous approach to AAA and renal cancer, with aneurismectomy performed
      first. In 2 cases a two-stage procedure was preferred; 1 patient underwent
      aneurismectomy first for AAA rupture while a second patient was even affected by
      gastric cancer and was submitted to nephrectomy and total gastrectomy as primary
      procedures. There was no mortality and only one postoperative complication was
      registered. CONCLUSIONS: A simultaneous surgical approach can be done safely,
      performing aneurismectomy as first step without significant risk of graft
      infection. Simultaneous treatment has the advantage of avoiding a second major
      abdominal procedure and eliminate the risk of postoperative aortic aneurysm
      rupture. Performing a two-stage approach, the procedure for the disease regarded
      as life-threatening is performed first. Priority should be given to renal cell
      neoplasm in selected cases.

PMID- 17043611
TI  - Early and medium-term results of stent-graft treatment of DeBakey type III aortic
      dissection.
AB  - AIM: The safety and effectiveness of transcatheter stent-graft treatment in the
      early and medium-term postoperative period was assessed in patients with DeBakey
      type III aortic dissection. METHODS: Transcatheter stent-graft implantation was
      performed in 37 patients who had aortic dissection with entry sites in the
      descending thoracic aorta. Entry sites were closed with a stent-graft consisting
      of a Gianturco Z stent covered with an UBE woven Dacron graft. RESULTS: There
      were no in-hospital deaths or serious complications after operation. In 5
      patients, a new intimal tear developed at the distal end of the stent-graft 8 to
      13 months after operation. It was closed by additional stent-graft placement in 2
      patients. The rate of thrombosis of the false lumen of the descending thoracic
      aorta 5 to 10 days, 3 to 6 months, and 12 months after operation was 70%, 80%,
      and 81%, respectively. As compared with before operation, the short axis of the
      true lumen increased (1.4+/-0.8 cm before operation, 2.1+/-0.5 cm at 5-10 days,
      and 2.7+/-0.6 cm at 3-6 months) and that of the false lumen decreased (2.9+/-0.9
      cm, 2.3+/-0.9 cm, 1.5+/-1.2 cm), indicating enlargement of the true lumen and
      shrinkage of the false lumen. The false lumen was completely obliterated within 3
      6 months after operation in 6 patients. CONCLUSIONS: Our early postoperative
      results show that transcatheter stent-graft implantation is a safe and effective
      procedure for the management of DeBakey Type III aortic dissection. Devices with
      a minimal risk of causing intimal tears should be developed.

PMID- 17043612
TI  - Risk factor analysis for ascending aorta and aortic arch repair using selective
      cerebral perfusion with open technique: role of open-stent graft placement.
AB  - AIM: The present study was designed to identify risk factors that may induce
      adverse outcome defined as permanent neurological dysfunction and mortality after
      aortic arch surgery using selective cerebral perfusion by logistic regression
      analysis and to reveal the role of open stent-graft placement. METHODS: One
      hundred and nineteen consecutive patients underwent ascending aorta and/or aortic
      arch operation with open technique between 1995 and 2005 were examined. Ascending
      aorta and/or hemiarch was replaced in 28 patients, total arch in 75 patients, and
      proximal or distal aortic arch replacement in 16 patients. Open stent-graft
      placement was used in 25 patients. RESULTS: The in-hospital mortality rate was
      9.2%. Permanent neurological dysfunction occurred in 10 patients (8.4%).
      Thoracotomy (P=0.0331) and cardiopulmonary bypass time (P=0.0238) were
      significant risk factors for permanent neurological dysfunction. Preoperative
      shock (P=0.0266) was significant independent risk factor for mortality. Emergent
      operation (P=0.0454), thoracotomy (P=0.0232), and cardiopulmonary bypass time
      (P=0.0379) were significant independent risk factors for adverse outcome. The
      duration of selective cerebral perfusion was not associated with adverse outcome.
      Open stent-graft placement has no need of thoracotomy for aneurysm extending
      descending thoracic aorta and time variables concerning the operation were
      significantly shorter in the patients with open stent-graft placement than in
      patients with standard operation for total arch replacement. RESULTS: Thoracotomy
      was significant risk factor for adverse outcome after aortic arch repair using
      selective cerebral perfusion. Total arch replacement with open stent-graft
      placement can avoid the need of thoracotomy and reduce time variables concerning
      the operation to improve the surgical

PMID- 17043613
TI  - Early graft thrombosis after endovascular aortic aneurysm repair with aortouni
      iliac endografts.
AB  - Endovascular repair of aortic aneurysm has become a viable treatment option in
      selected patients. However, despite the minimally invasive nature ot this
      treatment a significant incidence of vascular complications has been reported.
      Here, we report two cases of acute limbs ischemia due to endograft thrombosis in
      patients treated with aortouni-iliac devices and we review the etiologic factors
      related with these events and the treatment options. We suggest that the presence
      of atherosclerotic plaques within the outflow arteries and coexistent
      infrainguinal arterial occlusive disease (poor runoff) is an underestimated
      factor in the risk of graft thrombosis, especially in patients treated with
      aortouni-iliac devices and we advocate the use in the early follow-up
      surveillance after endovascular repair of aortic aneurysm of noninvasive test
      such duplex scanning, segmental pressures and ankle-brachial indices to asses the
      presence or progress of coexistent occlusive disease. We also suggest that some
      adverse outcomes ascribed to device failure might be more properly charged to
      inappropriate patient selection.

PMID- 17043614
TI  - Effect of cold blood cardioplegia enriched with potassium-magnesium aspartate
      during coronary artery bypass grafting.
AB  - AIM: The aim of this investigation is to evaluate the effect of enriched with
      potassium-magnesium aspartate cold-blood cardioplegia on early reperfusion injury
      and postoperative arrhythmias in patients with ischemic heart disease undergoing
      coronary artery bypass grafting (CABG), using measurements of cardiac troponin I
      (CTnI), hemodynamic indexes and clinical parameters. METHODS: Forty patients with
      three-vessel coronary artery disease (CAD) and stable angina, receiving first
      time elective CABG, were randomly divided into 2 groups: patients in control
      group (C group n=20) received routine institutional cold blood cardioplegia (4
      degrees C) concentration of Mg2+4 mmol/L, Ca2+1.2 mmol/L and K+ 24mmol/L during
      myocardial arrest. Patients in P group (n=20) received modified cold blood
      cardioplegia enriched with potassium-magnesium aspartate and maintained
      concentration of Mg2+10 mmol/L, Ca2+1.2 mmol/L and K+20mmol/L in the final blood
      cardioplegia solution. Clinical outcomes were observed during operation and
      postoperatively. Serial venous blood samples for CTnI were obtained before
      induction, after cardiopulmonary bypass (CPB), and postoperative 6, 24, and 72
      hours. Hemodynamic indexes were obtained before and after bypass by the radial
      catheter and Swan-Ganz catheter. RESULTS: In both groups, there were no
      differences regarding preoperative parameters. There were no cardiac related
      deaths in either group. The time required to achieve cardioplegic arrest after
      cardioplegia administration was significantly shorter in P group (47.5+/-16.3 s)
      than in C group (62.5+/-17.6 s) (P<0.01). The number of patients showing a return
      to spontaneous rhythm after clamp off was significantly greater in P group (n=20,
      100%) than in C group (n=14, 70%) (P<0.01). Eight patients in C group had atrial
      fibrillation (AF) compared with two patients in P group (P<0.05) in the early of
      postoperative period. The level of CTnI increased 6 hours and 12 hours
      postoperatively, and there was a significant difference between groups (P<0.05).
      P group also shortened the time of postoperative mechanical ventilation (P<0.05)
      after surgery. CONCLUSIONS: Cold blood cardioplegia enriched with potassium
      magnesium aspartate is beneficial on reducing reperfusion injury.

PMID- 17043615
TI  - Benefits of terminal noncardioplegic warm blood retrograde perfusion after
      terminal warm blood cardioplegia perfusion prior to aortic unclamping in open
      heart surgery.
AB  - AIM: The benefits of terminal noncardioplegic warm blood retrograde perfusion
      (TNWB) and terminal warm blood cardioplegia perfusion (TWBC) after intermittent
      cold blood cardioplegia perfusion during aortic clamping were studied. METHODS:
      The clinical results of consecutive 128 patients who underwent on pump coronary
      artery bypass grafting (CABG) or valvular surgery were studied retrospectively.
      The aortic cross-clamp was removed (1) after five-minute TWBC and sequential
      three-minute TNWB in 59 patients (TNWB group), (2) immediately after five-minute
      TWBC in 29 patients (TWBC group), or (3) with neither TWBC or TNWB in 36 patients
      (control group). RESULTS: The incidence of spontaneous heart beat recovery was
      best in TNWB group, second in TNBC, and worst in control group (TNWB: 86, TWBC:
      42, CONTROL: 14%). The duration from aortic unclamping to heart beat recovery was
      shorter in TNWB group than TWBC group (TNWB: 2.1, TWB: 4.3 min). Cardiopulmonary
      bypass duration after aortic unclamping was shortest in TNWB group, second in
      TWBC group, and longest in control group (TNWB: 21.3, TWB: 27.5, CONTROL: 46.9
      min). The postoperative CPK-MB was lowest in TNWB group (TNWB: 65.3, TWB: 87.7,
      CONTROL: 91.9U/L). Duration of intubation in TNWB group or TWBC group was shorter
      than control. CONCLUSIONS: Combination of the terminal noncardioplegic warm blood
      perfusion and terminal warm blood cardioplegic perfusion contributes to increase
      the incidence of spontaneous heart beat recovery, shortens cardiopulmonary bypass
      duration following aortic unclamping, and lowers postoperative CPK-MB.

PMID- 17043616
TI  - Incremental risk of obstructive sleep apnea on cardiac surgical outcomes.
AB  - AIM: Obstructive sleep apnea (OSA) is not generally acknowledged as a
      perioperative risk factor. High incidence of Sleep disordered breathing has been
      noticed in patients with cardiovascular disease. The Sleep Heart Health Research
      Study Group found Apnea-Hypopnea indices (AHI) as modest as 1-10 to be associated
      with cardiovascular disease manifestations. Given the lack of data we chose to
      study the incremental risk of OSA in patients undergoing cardiac surgery.
      METHODS: We looked at 25 587 patients who underwent cardiac surgery at the
      Cleveland Clinic. Of these, 37 patients were also identified on the Cleveland
      Clinic Sleep center database as having OSA. Each of these 37 cases were
      propensity matched for multiple covariates with 5 controls within a distance of
      0.001 units. An assumption was made that if the surgery was performed within two
      years of the diagnosis of OSA, the patient had OSA at the time of the surgery.
      RESULTS: Higher incidence of encephalopathy (p=0.008), postoperative infection
      (0.028) and increased ICU length of stay (p=0.031) were noted in the group with
      OSA after cardiac surgery. The difference in the rates of infection was mostly
      accounted for by the presence of mediastinitis (8.1% vs 1.6%). Differences in the
      rates of reintubation, tube time, and overall postoperative morbidity were not
      statistically significant. CONCLUSIONS: | Increased risk for postoperative
      complications is suggested in patients with OSA undergoing cardiac surgery. This
      risk is underestimated on account of lack of awareness about the incidence of OSA
      in the general population and the cardiovascular population in particular,
      difficulties in clinical suspicion and diagnosis and limited use of
      polysomnography.

PMID- 17043617
TI  - Nine years experience of aortic arch repair with the aid of antegrade selective
      cerebral perfusion.
AB  - AIM: Antegrade selective cerebral perfusion (ASCP) is gaining widespread
      popularity in aortic arch surgery because it has been demonstrated to be an
      optimal technique of cerebral protection. This study demonstrates the clinical
      results of aortic arch repair with ASCP. METHODS: Between November 1996 and
      September 2004, 250 patients underwent thoracic aorta replacement using ASCP
      under moderate hypothermia. Mean patients age was 63+/-11.5 years. Presenting
      pathologies were chronic aneurysm in 136 patient (54.4%), type A acute aortic
      dissection in 80 patients (32%), post-dissection aneurysm in 30 patients (12%).
      Ascending aorta and hemiarch replacement was performed in 63 patients (25.2%),
      ascending aorta and total arch replacement in 131 patients (52.4%), total arch
      replacement in 33 patients (13.2%), total arch and descending aorta replacement
      in 10 patients (4%) and complete replacement of the thoracic aorta in 13 patients
      (5.2%). RESULTS: Hospital mortality was 11.6%. Multivariate analysis showed
      preoperative renal failure (P=0.050), cerebral perfusion time (P<0.001),
      pulmonary complications (P=0.009) and postoperative dialysis (P=0.030) as risk
      factors for hospital mortality. Permanent neurologic deficits occurred in 4
      patients (1.6%) and coronary artery disease (P=0.029) was found to be the only
      independent risk factor. Transient neurologic deficits were noted in 18 patients
      (7.2%). Multivariate analysis revealed age (P=0.043), coronary artery disease
      (P=0.036), urgent/emergency status of the operation (P=0.016) and concomitant
      aortic valve replacement (P=0.001) to be independent predictors of transient
      neurologic dysfunction. The actuarial survival rate at 7 years was 61.7%.
      CONCLUSIONS: | Our results confirmed that ASCP is a safe method of brain
      protection allowing complex aortic repairs to be performed with good results in
      terms of hospital mortality and neurologic outcome. Cerebral perfusion time did
      not influence postoperative outcome. The use of moderate hypothermia avoided all
      undesirable effects of deep hypothermia.

PMID- 17043618
TI  - Extracardiac Fontan operation without cardiopulmonary bypass.
AB  - AIM: The avoidance of cardiopulmonary bypass and aortic cross-clamping in
      patients possessing single ventricular physiology has potential advantages
      including preservation of ventricular and pulmonary functions; early extubation,
      decreased incidence of pleural effusions and decreased requirement of inotropic
      agents and blood products. In this study, we assessed the postoperative outcome
      of patients who have undergone extracardiac Fontan operation performed without
      cardiopulmonary bypass. METHODS: Between March 1999 and August 2002, 10
      consecutive patients (6 males and 4 females) underwent extracardiac Fontan
      operation without cardiopulmonary bypass. The age of patients ranged between 1.5
      to 12 (5.2+/-3.1) years. All the patients requiring any intracardiac intervention
      were excluded from the study. Previous operations of the patients were modified
      Blalock-Taussig shunt procedure in 3 patients, bidirectional cavopulmonary shunt
      operation in 2 patients and pulmonary arterial banding in 1 patient. All
      operations were performed without cardiopulmonary bypass. Bidirectional
      cavopulmonary anastomosis was performed by using a transient external shunt
      constructed between the superior vena cava and right atrium. An appropriate sized
      tube graft was anastomosed to the inferior surface of right pulmonary artery.
      Finally, inferior vena cava to tube grafts anastomosis was performed with the aid
      of another external shunt constructed between inferior vena cava and right
      atrium. During the procedure central venous pressure, blood pressure and arterial
      oxygen saturation levels were continuously monitored and recorded. RESULTS: The
      mean intraoperative Fontan pressure was 16.1+/-2.75 mmHg. Intraoperative
      fenestration was required in 4 patients with a Fontan pressure above 18 mmHg.
      There were no intra and postoperative deaths. Three patients required mild doses
      of inotropic support during the postoperative period. All patients were weaned
      off mechanical ventilation within 24 h. The mean arterial oxygen saturation
      raised from 74.5+/-4.2% to 93.5+/-2%. Arterial oxygen saturation was 95+/-0.6% in
      6 patients without fenestration and 91.2+/-0.5% in 4 patients with fenestration
      (P=0.001). All patients were in sinus rhythm postoperatively. Only 2 patients
      required blood transfusion. Two patients suffered from prolonged pleural effusion
      (more than 7 days). The mean intensive care unit and hospital stay periods were
      3.3+/-1.5 and 15.4+/-5.3 days, respectively. CONCLUSIONS: The extracardiac Fontan
      operation performed without cardiopulmonary bypass provides good results in short
      and midterm follow-up periods with improved postoperative hemodynamics.

PMID- 17043619
TI  - Surgical treatment of atrial fibrillation with bipolar radiofrequency ablation:
      mid-term results in one hundred consecutive patients.
AB  - AIM: The Cox-Maze procedure was introduced nearly two decades ago for the
      surgical treatment of atrial fibrillation (AF). Recently, our group has replaced
      most of the incisions of the Cox-Maze procedure with bipolar radiofrequency (RF)
      ablations (Cox-Maze IV procedure). The purpose of this study was to examine our
      midterm results with the Cox-Maze procedure using bipolar RF ablation. METHODS:
      From January 2002 to October 2005, 100 consecutive patients underwent a modified
      Cox-Maze procedure with bipolar RF ablation for AF; 32 were lone operations, and
      68 were concomitant procedures. Follow-up was performed at 1, 3, 6, and 12
      months, and then annually thereafter. Heart rhythm was confirmed by
      electrocardiography. RESULTS: The mean age of patients was 62+/-13 years; 57%
      were male. Duration of AF was 6.3+/-7.6 years (0.1 to 40 years), 59% had
      paroxysmal AF, and 34% had permanent AF. Follow-up was complete for all patients
      with a mean follow-up of 13+/-10 months. At 12-month follow-up, 91% (49/54) of
      patients were free of AF. Cross-clamp time in the lone Cox-Maze IV procedure
      patients was 42+/-15 minutes, while it was 101+/-29 minutes for the Cox-Maze IV
      with a concomitant procedure (compared to 93+/-34 minutes and 122+/-37 minutes
      for the traditional procedure, P<0.05). There were four operative deaths.
      CONCLUSIONS: The Cox-Maze IV procedure had good mid-term efficacy. The use of
      bipolar RF energy significantly decreased operative time and simplified the
      procedure compared to the traditional Cox-Maze procedure, potentially increasing
      utilization of the procedure among cardiac surgeons.

PMID- 17043620
TI  - A multi-step approach in anti-calcification of glutaraldehyde-preserved bovine
      pericardium.
AB  - AIM: Bioprosthetic cardiovascular substitutes, manufactured from glutaraldehyde
      preserved bovine or porcine tissues, are prone to calcification after
      implantation. The aim of the study was to evaluate the ultrastructure, material
      stability and calcification behaviour of glutaraldehyde-preserved bovine
      pericardium, treated with a multi-step anti-calcification process which addresses
      each of the major causes of calcification and tissue degeneration. METHODS:
      Bovine pericardium samples were divided into 2 groups. Group I (control)
      consisted of tissue fixed with 0.625% glutaraldehyde and Group II (study group)
      consisted of tissue fixed with 0.625% glutaraldehyde and exposed to a multi-step
      anti-calcification process. Ultrastructure was examined by scanning electron
      microscopy and material stability was assessed by mechanical testing, shrinkage
      temperature and enzymatic degradation. Calcification was assessed by histology
      (Von Kossa stain) and by atomic absorption spectrophotometry in the subcutaneous
      rat model. RESULTS: Bovine pericardium in the study group revealed less visible
      changes in the ultrastructure of the collagen matrix, improved material stability
      (P<0.05) and significantly (P<0.001) reduced calcification compared to control
      tissues (4.5+/-1.2 versus 136.03+/-11.39 ug/mg tissue). CONCLUSIONS: In
      conclusion, results demonstrate that the multi-step anticalcification process
      improved the material stability and reduced the calcification potential of bovine
      pericardial tissue. These improvements in the quality of the bovine pericardium
      should enhance the long-term durability of the tissue as a bioprosthetic
      substitute for cardiovascular application.

PMID- 17043622
TI  - Communicating across the boundaries.

PMID- 17043621
TI  - Comparison of a beta-blocker and an If current inhibitor in rabbits with
      myocardial infarction.
AB  - AIM: We compared protective effects of a ss-adrenoceptor blocker (metoprolol;
      Met) and a If current (Ivabradine; Iva) in a rabbit model of myocardial
      infarction. METHODS: Experiments were performed on 44 adult New-Zealand-White
      (NZW) rabbits. The effects of either metoprolol or ivabradine were assessed 15
      min after experimental occlusion of a coronary artery (CAO), 28 days after CAO
      (drug gavage), and in vitro hearts (Langendorff apparatus). The results were
      compared with sham and placebo hearts. RESULTS: Metoprolol (0.25 mg/kg) slightly
      reduced heart rate and left ventricular systolic function. Ivabradine (0.25
      mg/kg) reduced heart rate significantly (P<0.05) (18% vs control). Both drugs
      provided advantages over placebo: mortality was significantly (P<0.01)smaller
      (6/13 Pla animals died, 2/10 Met animals, and 3/11 Iva animals), left ventricular
      function was better preserved after 28 days (external power; Pla; Met; Iva=56%;
      76%; 74%), and dilatation (BNP) was reduced (P<0.05). In the Pla group, the ST
      segment was significantly (P<0.05) elevated by 0.35 mV after CAO and exhibited in
      50% of the animals Q waves after 28 days, while after ivabradine or metoprolol,
      ST displacement and Q waves had disappeared. The uneconomic myosin isoenzyme V3
      predominated in Met hearts and Iva hearts (V3/V1: 63/37% and 62/38%), while it
      was further increased in Pla hearts (78/21%). External efficiency was lowest in
      Pla hearts (1.00+/-0.50 a.u.; P<0.05) and was significantly higher both in Met
      hearts (4.0+/-1.8 a.u.) and in Iva hearts (3.3+/-1.6 a.u.). CONCLUSIONS: Met and
      Iva seem suited for the treatment of chronic myocardial infarction.

PMID- 17043623
TI  - Advances in cancer therapy with radiolabeled monoclonal antibodies.
AB  - Two radiolabeled antibody products for the treatment of non-Hodgkin's lymphoma
      have been approved, thus indicating that cancer radioimmunotherapy (RAIT) has
      finally come of age as a new therapeutic modality, exemplifying the collaboration
      of multiple disciplines, including immunology, radiochemistry, radiation
      medicine, medical oncology, and nuclear medicine. Clinical trials are showing
      usefulness in other hematological neoplasms, but the treatment of solid tumors
      remains the major challenge, since the doses shown to be effective in
      hematological tumors are insufficient in the more common epithelial cancers.
      Nevertheless, use of RAIT in locoregional applications and in the treatment of
      minimal residual disease have shown promising RESULTS: There is also optimism
      that pretargeting procedures, including new molecular constructs and targets,
      will improve the delivery of radioactivity to tumors with less hematologic
      toxicity, and thus may become the next generation of RAIT.

PMID- 17043624
TI  - Practical aspects of peptide receptor radionuclide therapy with [177Lu][DOTA0,
      Tyr3]octreotate.
AB  - Lutetium-177 is increasingly used in patients for receptor-targeted radionuclide
      therapy with peptides such as [DOTA0,Tyr3]octreotate. In our therapy facility, we
      are performing yearly 400 treatments with each 7.4 GBq
      [177Lu][DOTA0,Tyr3]octreotate. Finger dosimetry data during radiolabeling reveal
      higher doses on the right hands of right-handed workers with the highest
      equivalent dose for the middle finger (53+/-12 microSv/GBq). Extrapolating
      dosimetry data, assuming 400 doses of 7.4 GBq per year performed by 4 workers,
      result in a mean equivalent dose of 23+/-11 mSv and 14+/-6 mSv for finger top and
      ring dose, respectively. Preparation of 400 doses will result in an effective
      dose of 0.5-1.5 mSv per year for these 4 workers. The extra radiation dose for
      workers during the radiolabeling of these doses thus remains below 10% of the
      legal annual limits, which is in accordance with the ALARA optimization
      principle. Based on measurements of the maximal radiation level at 1 m distance
      (7.5+/-3.6 microSv/h), patients treated with 7.4 GBq
      [177Lu][DOTA0,Tyr3]octreotate can already leave the therapy facility the next
      day. As radioactive waste streams are based on the half-lives of the used
      radionuclides, 177Lu-waste (t1/2=6.7 d) was initially collected along with the
      131I-waste (t1/2=8 d). According to both manufacturers' specifications, 177Lu
      contains less than 0.4 kBq 177mLu/MBq 177Lu (at the end of neutron irradiation),
      when produced by the [176Lu n, gamma 177Lu] reaction via thermal neutron
      bombardment of enriched lutetium oxide. Unfortunately, because of the huge
      amounts of 177Lu used, contaminating 177mLu turned out to prevent the quick
      discharge of this waste, for some containers even after some years of storage.
      Therefore, a technique for calibrating 177mLu was developed, simultaneously
      confirming the manufacturer's specifications on the presence of 177mLu in 177Lu.
      Subsequently a reliable technique was developed to measure 177mLu in waste
      containers using a beta/gamma-contamination monitor. It is advised to collect
      177mLu/177Lu-waste and certainly high-activity lutetium waste separated from 131I
      according the regulations in the country of use. Apart from the mentioned waste,
      excreta from patients are collected in decay tanks, where they are stored for 1-2
      months before they are discarded into the general sewer within the overall
      tolerated discharge limit (150 radiotoxicity equivalents/year for our
      department).

PMID- 17043625
TI  - Peptide receptors in neuroendocrine tumors of the lung as potential tools for
      radionuclide diagnosis and therapy.
AB  - Neuroendocrine tumors of the lung are carcinomas characterized by different
      impact on the patients' prognosis, ranging from relatively indolent, low- to
      intermediate-grade neoplasms with longer life expectation (i.e., typical and
      atypical carcinoids) to very aggressive and poorly differentiated neoplasms with
      dismal prognosis (i.e., large cell neuroendocrine carcinoma and small cell lung
      cancer). The standard treatment of typical or atypical carcinoids is the complete
      surgical resection, whereas the role of radio-chemotherapy in a multimodality
      treatment or for palliation remains controversial. Conversely, high-grade
      neuroendocrine carcinomas are in primis treated by aggressive combination
      chemotherapy, deserving surgical resection for uncommon low-stage tumors. Since
      evidence has been accumulated that neuroendocrine tumors of the lung are supplied
      with a wide array of peptide receptors detectable on cell membranes by
      immunohistochemical methods, innovative strategies for diagnosis and
      radiometabolic therapy have been devised to target these molecules for the
      correct clinical management of the patients. In this paper, the structural and
      functional aspects and the clinical applications of the detection of several
      peptide receptors in pulmonary neuroendocrine tumors will be reviewed, including
      somatostatin receptors, vasoactive intestinal peptide/pituitary adenylate cyclase
      activating peptide family receptors, cholecystokinin /gastrin receptors,
      bombesin/gastrin releasing peptide receptors, neurotensin receptors, substance P
      receptors, neuroepeptide Y receptors, calcitonin/calcitonin gene-related peptide
      receptors, atrial natriuretic peptide receptors, glucagon-like-peptide-1
      receptors, oxytocin receptors and endothelin receptors. Only a detailed knowledge
      of the peptide receptor distribution in these tumor types, especially in uncommon
      neoplasms such as atypical carcinoids and large cell neuroendocrine carcinomas,
      is pivotal for planning the most adequate interventions for the patients'
      diagnosis and therapy.

PMID- 17043626
TI  - Systemic and locoregional dosimetry in receptor radionuclide therapy with
      peptides.
AB  - This paper reviews the methods for calculating dosimetry both after systemic or
      locoregional injection of radiolabelled peptides. Radiopharmaceutical
      characteristics, data processing and dosimetric outcomes are reported. The
      biological effective dose, based on the linear quadratic model, is finally
      described.

PMID- 17043627
TI  - Vascular tumor targeting.
AB  - The growth of solid tumors is dependent on their capacity to acquire blood
      supply. Therefore, much effort has been directed towards the development of anti
      angiogenic agents which inhibit the process of neovascularization. More recently,
      it has become apparent that the targeted destruction of the established tumor
      vasculature represents a complementary avenue for growing therapeutic
      opportunities. This review provides evidence that vascular tumor targeting is an
      effective anti-tumor strategy in animal models. It further describes strategies
      for the identification of putative tumor vascular targets and discusses future
      prospects for vascular targeting applications in the clinical setting.

PMID- 17043628
TI  - Lutetium-177-labeled gastrin releasing peptide receptor binding analogs: a novel
      approach to radionuclide therapy.
AB  - Optimization of therapy for individual patients remains a goal of clinical
      practice. Radionuclide imaging can identify those patients who may benefit from
      subsequent targeted therapy by providing regional information on the distribution
      of the target. An ideal situation may be when the imaging and the therapeutic
      compounds are the same agent. Two antibodies ([ [90Y]ibritumomab,
      [131I]tositumomab) are now approved for the systemic radiotherapy of non
      Hodgkin's lymphoma. The main hurdle is to deliver higher absorbed doses to the
      more refractory solid tumors paying particular regard to the bone marrow
      toxicity. The low dose is thought to be a result of the large size of antibodies
      slowing delivery to the target. Peptides having high affinity to receptors
      expressed on cancer cells are a promising alternative. They are usually rapidly
      excreted from the body through renal and/or hepatobiliary excretion thus creating
      a prolonged accumulation of the radioactivity in the kidneys, which represents a
      recognized issue for systemic radiotherapy. The first radiopeptide developed was
      a somatostatin analogue, which led to a major breakthrough in the field. Beside
      the kidney issue, somatostatin use remains limited to few cancers that express
      receptors in sufficiently large quantities, mainly neuroendocrine tumors. The
      gastrin releasing peptide (GRP) receptor is an attractive target for development
      of new radiopeptides with diagnostic and therapeutic potential. This is based
      upon the functional expression of GRP receptors in several of the more prevalent
      cancers including prostate, breast, and small cell lung cancer. This review
      covers the efforts currently underway to develop new and clinically promising GRP
      receptor specific molecules labeled with imageable and therapeutic radionuclides.

PMID- 17043629
TI  - Current status and perspectives in alpha radioimmunotherapy.
AB  - Systemic administration of radiolabeled antibody directed against tumor antigens
      in radioimmunotherapy (RIT) enables to specifically target the cancer cells and
      to destroy them. So far, this strategy has proven its efficiency in the treatment
      of some hematological cancers with antibodies labeled with beta emitting
      radionuclides. In the last 2 decades, availability of short half life alpha
      emitters prompted to consider their use in RIT. Contrary to beta particles, alpha
      particles have a short path length and display a high lineic energy transfer.
      Those physical characteristics open new fields of clinical applications
      complementary to beta-RIT. To date, alpha-RIT is still at a preclinical stage of
      development: the radiolabeling methods need to be optimized to ensure in vivo
      stability of the radiopharmaceuticals. Some radionuclides have complex decay
      schemes with daughters emitting further alpha particles whose toxicity needs to
      be investigated. The modalities of administration of radiolabeled antibodies in
      animal models require also to be improved for delivering higher doses to tumor
      targets. A comprehensive analysis of the specific events occurring at cell or
      tissue level in response to alpha irradiation would be of great interest in order
      to define the best therapeutic association for residual disease or consolidation
      treatments. This approach has been proven to be efficient in increasing antitumor
      response either by using high doses with organ protection (kidney, bone marrow)
      or by a synergistic effect between alpha-RIT and associated treatments, such as
      chemotherapy.

PMID- 17043630
TI  - Platelet function after single [153Sm]EDTMP therapy in prostate cancer.
AB  - AIM: Aim of the study was to assess whether [153Sm] EDTMP therapy at a low-dose
      is associated with platelet activation. METHODS: In 29 patients suffering from
      metastatic prostate cancer platelet count and various platelet function
      parameters have been monitored for 2 months after a single (the first)
      application of 1.1 GBq mCi [153Sm]EDTMP. RESULTS: After 3 days insignificant
      signs of platelet activation (increase in malondialdehyde, adenosine diphosphate
      induced platelet aggregation, decreased platelet sensitivity) occur, normalizing
      rapidly. At the nadir of platelet count (3-4 weeks) platelet aggregation response
      in non-count adjusted samples is somewhat lower, while activity per cell (count
      adjusted samples) is unchanged. Platelet proteins do not change at all.
      Insignificant activation of platelet function at day 3 is interpreted as an
      indicator of mild oxidation injury, late aggregation response changes in non
      adjusted samples seem only to reflect temporarily decreased number of circulating
      platelets. Samarium-153-EDTMP therapy at doses (1.1 GBq) used in the Vienna
      protocol is not associated with a significantly altered functional behavior of
      platelets. CONCLUSIONS: We conclude that a single dose of 1.1 GBq 153Sm-EDTMP
      does not significantly affect in vivo and ex vivo platelet function.

PMID- 17043631
TI  - Modification of low-density lipoprotein during radiolabeling with 99mTc using
      three labeling methods.
AB  - AIM: The mechanisms of native low-density lipoprotein (LDL) uptake by monocytes
      and macrophages via the specific cholesterol down-regulated LDL-receptor differs
      form the mechanism responsible for the unregulated scavenging of the modified,
      for example, oxidized LDL, by the atherosclerotic plaques and foam cells. For
      this reason, we investigated if the 99mTc-labeled LDL stands for the native or
      modified molecule. The influence of the LDL sampling methods, isolation,
      preparation and radiolabeling of lipoproteins on structure modification and the
      subsequent imaging behavior has as yet not been addressed in detail. METHODS:
      Herein we present data on the effects of 99mTc labeling on some oxidation
      relevant parameters of LDL, such as the lag-time, thiobarbituric acid reactive
      substances (TBARS), relative electrophoretic mobility (REM), baseline dienes
      (BD), lipid peroxides (POX), free amino-groups (NH2-groups) and free sulphydryl
      groups (SH-groups). Three methods of 99mTc labeling were compared: dithionite
      method (1), borohydride method (2) and ascorbic acid method (3). Data for
      oxidation parameters are expressed as a percent of freshly isolated native LDL (%
      native LDL) or as a percent of LDL treated with the labeling buffers and
      reagents, but in absence of the radioisotope (% control LDL). RESULTS: The levels
      of BD were most influenced by methods 2 and 3, and remained almost unchanged when
      the method 1 was used. The lag-time of 99mTc-LDL produced by method 2 doubled but
      it was decreased by 23% when the method 3 was employed. No change in the lag-time
      compared to the native LDL was observed with the method 1. The TBARS levels were
      3-5 fold higher than in native LDL when methods 1 and 2 were used, but 33% lower
      in products made by the method 3. The number of thiol groups increased 3 fold in
      method 1, was only slightly elevated in method 3, but reduced in method 2
      compared to native LDL. NH2-groups were increased with all three labeling
      procedures, but this increase was not considered significant. REM was altered
      only in products obtained by methods 1 (1.5x increase) and by method 2 (1.25x
      increase). No fragmentation of Apo B using sodium dodecyl sulfate polyacrylamide
      gel (SDS-PAGE) electrophoresis was observed by 99mTc-LDL produced in any of the
      METHODS: The increase of lipid peroxide generation was observed only when the
      method 2 was used. CONCLUSIONS: Of the three tested methods, we found all of them
      to render LDL oxidatively modified to some extent. Therefore, it appears that the
      native-LDL imaging with 99mTc-labeled LDL is impossible. Only the ascorbic acid
      method 3 appears to offer some protection and exerts antioxidant effects.

PMID- 17043632
TI  - Chromogranin A immunoradiometric assay in diagnosis of pheochromocytoma:
      comparison with plasma metanephrines and 123I-MIBG scan.
AB  - AIM: The aim of this study is to investigate the diagnostic performance of serum
      chromogranin A (CgA) and plasma metanephrines (MN) assays in the diagnosis of
      pheochromocytoma. METHODS: We enrolled 44 patients affected by histologically
      proved adrenal pheochromocytoma. All patients underwent abdominal computed
      tomography and whole body 123I-MIBG scan to stage the disease. One hundred
      healthy blood donors and 148 patients affected by essential hypertension were
      enrolled as controls. Serum CgA and plasma MN were assayed by immunoradiometric
      assay (IRMA) and high-performance liquid chromatography. Cut-off levels were
      selected to obtain 99% specificity in healthy control subjects. RESULTS: Both MN
      and CgA showed 95% sensitivity with comparable high specificity and diagnostic
      accuracy (96% and 96% for CgA, 94% and 95% for MN, respectively). By employing
      both markers and considering CgA or MN positivity, a 100% sensitivity was
      obtained with 95% accuracy. MN and CgA concentration clearly increased from
      controls to patients with pheochromocytomas (P<0.0001). A relationship between
      serum CgA (but not MN) and tumor mass was found (P<0.0001). CONCLUSIONS: Both
      markers are sensitive and specific in chromaffin-tumors detection: CgA IRMA assay
      employed a simple and feasible technology and showed to be as sensitive and
      slightly more accurate than MN.

PMID- 17043633
TI  - Value of thyroglobulin to 131I uptake ratio in selection of initial therapy dose
      of 131I in patients with differentiated thyroid carcinoma.
AB  - AIM: To test the hypothesis that the ratio of thyroglobulin (Tg) to 131I uptake
      in the thyroid bed during the immediate post-thyroidectomy work-up could be used
      before first 131I treatment to detect patients with residual or metastatic
      thyroid cancer and justify the administration of a higher ablation dose in
      selected cases and a possibly better therapeutic effect. METHODS: We
      retrospectively studied 293 patients with differentiated thyroid carcinoma that
      received their first 131I treatment in our department. Patients with Tg >100
      ng/mL, 131I uptake >10% and measurable Tg-specific autoantibodies, were excluded.
      According to the post-therapy total body scan (TBS), we divided them in 2 groups:
      group I, without metastases (negative TBS), and group II, with metastases
      (positive TBS). The ratio of Tg to 131I uptake measured before the first 131I
      treatment was calculated in both groups. RESULTS: A total of 248 patients were
      included in the study; 225 in group I and 23 in group II. Tg to 131I uptake ratio
      was significantly lower in group I (mean 2.17 ng/mL/%, range 0-36), than in group
      II (mean 32.7 ng/mL/%, range 2.14-220), (P<0.01). The sensitivity, specificity
      and accuracy (using a threshold ratio 7 ng/mL/% as normal) were all 95.6% for
      predicting a positive post-therapy TBS. CONCLUSIONS: The use of a threshold ratio
      7 ng/mL/% as the upper limit of normal provides useful information with higher
      sensitivity and specificity in identifying patients with metastatic disease
      creating the possibility for the selective use of higher initial iodine therapy
      doses.

PMID- 17043634
TI  - [186Re]HEDP in the palliation of painful bone metastases from cancers other than
      prostate and breast.
AB  - AIM: Palliative therapy using [186Re]hydroxyethylidene diphosphonate (HEDP) has
      been widely tested in patients with bone metastases from prostate and breast
      cancers. Whereas, to the best of our knowledge, only few cases of bone metastases
      from tumors other than prostate and breast treated with [186Re]HEDP have been
      reported. The aim of this paper is to report our experience with 186Re-HEDP in
      the palliation of painful bone metastases from tumors other than prostate and
      breast. METHODS: In this study 41 patients (17 non-small cell lung cancer-NSCLC,
      1 small cell lung cancer, 1 lung neuroendocrine tumor, 8 bladder cancer, 3 kidney
      cancer, 3 gastric cancer, 1 uterine carcinoma, 1 colon cancer, 1 rhinopharynx
      carcinoma, 1 medullary thyroid carcinoma, 1 ovarian cancer, 1 esophagus cancer, 2
      carcinoma of unknown origin) are evaluated. All patients had lesions with
      increased [99mTc]MDP uptake and none had radiological findings of mainly
      osteolytic lesions. A total of 46 therapeutic cycles were performed using a
      [186Re]HEDP activity of 1 295 MBq for each administration. After treatment,
      patients were followed up for 3 months or to the time of pain recurrence (if
      longer than 3 months). Responses were evaluated using a validated method
      considering the modifications of pain index, analgesic intake and performance
      status. RESULTS: Treatment efficacy was complete in 49% (20/41) of patients,
      partial in 36% (15/41) and negative in 15% (6/41). Namely, we observed 35% (6/17)
      complete, 41% (7/17) partial and 24% (4/17) negative responses in patients with
      NSCLC and 63% (5/8) complete, 25% (2/8) partial and 12% (1/8) negative responses
      in patients affected by bladder cancer. The median duration of pain relief in
      responder patients was 10 weeks. A mild platelet toxicity occurred in 32% (13/41)
      of patients. CONCLUSIONS: Pain palliation with [186Re]HEDP seems highly effective
      and safe also in patients with bone metastases from cancers other than prostate
      and breast. Patients who can benefit from the treatment with [186Re]HEDP can be
      selected on the basis of [99mTc]MDP bone scan and radiological examination
      findings.

PMID- 17043635
TI  - Iodine-131 pharmacokinetics in patients on hemodialysis for end stage renal
      disease: clinical implications.
AB  - AIM: Curative treatment of thyroid cancer is a major issue for patients with end
      stage renal disease (ESRD) undergoing dialysis because they might not be included
      in a renal transplant protocol once they have overcome this disease. Since 131I
      is mostly eliminated by the kidneys, there is concern regarding the toxicity,
      efficacy and feasibility of 131I-therapy of anuric dialyzed patients. METHODS:
      This paper reports on 131I uptake and elimination from remnant thyroid tissue
      (T), salivary glands (SG), stomach (S) and blood, after administration of 3.7 GBq
      of 131I for 2 patients on twice weekly dialysis for ESRD. RESULTS: Compared to
      normal renal function patients, radio-iodine recirculation is observed, and SG
      and blood irradiation is about 6 times higher, but the dose delivered to the
      thyroid is not significantly enhanced. Dialysis removes more 131I from SG, S and
      blood than from T. Anticipated dialysis will reduce irradiation by 38% for the
      blood, 45% for SG and 34% for T. CONCLUSIONS: Therefore, a higher 131I amount
      could then be used, providing that accurate personalized dosimetry is previously
      performed using 131I pharmacokinetic models. Concerning radiation protection
      issues, no significant dialysis equipment contamination is noted, and nurses and
      medical staff exposure remains below 0.2 mSv.

PMID- 17043636
TI  - Diversity of TMPRSS2-ERG fusion transcripts in the human prostate.
AB  - TMPRSS2-ERG gene fusions have recently been reported to be present in a high
      proportion of human prostate cancers. In the current study, we show that great
      diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found
      in human prostates. Fourteen distinct hybrid transcripts are characterized, each
      containing different combinations of sequences from the TMPRSS2 and ERG genes.
      The transcripts include two that are predicted to encode a normal full-length ERG
      protein, six that encode N-terminal truncated ERG proteins and one that encodes a
      TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid
      transcripts were found in samples taken from separate regions of individual
      cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be
      arising independently in different regions of a single prostate.

PMID- 17043637
TI  - Urokinase receptor primes cells to proliferate in response to epidermal growth
      factor.
AB  - Epidermal growth factor (EGF) expresses mitogenic activity by a mechanism that
      requires the EGF receptor (EGFR). We report that murine embryonic fibroblasts
      (MEFs) proliferate in response to EGF only when these cells express the urokinase
      receptor (uPAR). EGFR expression was equivalent in uPAR-/- and uPAR+/+ MEFs. In
      response to EGF, these cells demonstrated equivalent overall EGFR tyrosine
      phosphorylation and ERK/MAP kinase activation; however, phosphorylation of Tyr
      845 in the EGFR, which has been implicated in cell growth, was substantially
      decreased in uPAR-/- MEFs. STAT5b activation also was decreased. As Tyr-845 is a
      c-Src target, we overexpressed c-Src in uPAR-/- MEFs and rescued EGF mitogenic
      activity. Rescue also was achieved by expressing murine but not human uPAR,
      suggesting a role for autocrine uPAR cell-signaling. In MDA-MB 231 breast cancer
      cells, EGF mitogenic activity was blocked by uPAR gene silencing, with antibodies
      that block uPA-binding to uPAR, and with a synthetic peptide that disrupts uPAR
      dependent cell signaling. Again, c-Src overexpression rescued the mitogenic
      activity of EGF. We conclude that uPAR-dependent cell-signaling may prime cells
      to proliferate in response to EGF by promoting Tyr-845 phosphorylation and STAT5b
      activation. The importance of this pathway depends on the c-Src level in the
      cell.

PMID- 17043638
TI  - The immunoglobulin heavy-chain gene 3' enhancers deregulate bcl-2 promoter usage
      in t(14;18) lymphoma cells.
AB  - In t(14;18) lymphomas, bcl-2 is juxtaposed to the immunoglobulin heavy-chain gene
      (IgH), resulting in increased bcl-2 transcription and resistance to apoptosis.
      Regulatory elements of both the bcl-2 promoter and the IgH enhancers are believed
      to play a role in the increased expression of bcl-2 in t(14;18) lymphoma cells.
      In addition, transcription of the translocated bcl-2 allele is deregulated with
      activation of the normally minor bcl-2 P2 promoter. The mechanisms involved in
      the promoter shift from P1 to P2 are not known. We found that the murine IgH 3'
      enhancers increased bcl-2 P2 promoter activity in an episomal model of the
      translocation, and IgH enhancer region HS12 had the greatest effect. Quantitative
      chromatin immunoprecipitation (ChIP) assays revealed that localized histone H3
      hyperacetylation of the P2 promoter was observed on the translocated allele in
      t(14;18) DHL-4 cells and also on the stably transfected bcl-2 promoter-IgH
      enhancer episomal construct. Analysis of the HS12 enhancer region revealed that a
      previously identified nuclear factor-kappaB (NF-kappaB) site and a previously
      uncharacterized downstream Cdx site, both of which are conserved in the human and
      murine IgH enhancers, were important for its enhancer activity and promoter
      activation. ChIP assays showed that C/EBPbeta bound to the HS12 Cdx site in vivo,
      and mutation of this site abrogated the binding of C/EBPbeta. Reduced expression
      of C/EBPbeta by transfection of small interfering RNA or interference with NF
      kappaB activity decreased transcription from the bcl-2 promoters. These results
      demonstrate that the IgH 3' enhancers, particularly HS12, are important for the
      deregulation of bcl-2 promoter usage in t(14;18) lymphomas.

PMID- 17043639
TI  - Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression
      profiling.
AB  - We have assessed the possibility to build a prognosis predictor (PP), based on
      non-neoplastic mucosa microarray gene expression measures, for stage II colon
      cancer patients. Non-neoplastic colonic mucosa mRNA samples from 24 patients (10
      with a metachronous metastasis, 14 with no recurrence) were profiled using the
      Affymetrix HGU133A GeneChip. Patients were repeatedly and randomly divided into
      1000 training sets (TSs) of size 16 and validation sets (VS) of size 8. For each
      TS/VS split, a 70-gene PP, identified on the TS by selecting the 70 most
      differentially expressed genes and applying diagonal linear discriminant
      analysis, was used to predict the prognoses of VS patients. Mean prognosis
      prediction performances of the 70-gene PP were 81.8% for accuracy, 73.0% for
      sensitivity and 87.1% for specificity. Informative genes suggested branching
      signal-transduction pathways with possible extensive networks between individual
      pathways. They also included genes coding for proteins involved in immune
      surveillance. In conclusion, our study suggests that one can build an accurate PP
      for stage II colon cancer patients, based on non-neoplastic mucosa microarray
      gene expression measures.

PMID- 17043640
TI  - Human cancer cells require ATR for cell cycle progression following exposure to
      ionizing radiation.
AB  - The vast majority of cancer cells have defective checkpoints that permit the cell
      cycle to progress in the presence of double-strand DNA breaks (DSBs) caused by
      ionizing radiation (IR) and radiomimetic drugs. ATR (ataxia telangiectasia
      mutated and Rad3-related) has recently been shown to be activated by DSBs,
      although the consequences of this activity are largely unknown. In this report,
      we use advanced gene targeting methods to generate biallelic hypomorphic ATR
      mutations in human colorectal cancer cells and demonstrate that progression of
      the cancer cell cycle after IR treatment requires ATR. Cells with mutant ATR
      accumulated at a defined point at the beginning of the S phase after IR treatment
      and were unable to progress beyond that point, whereas cells at later stages of
      the S phase during the time of irradiation progressed and completed DNA
      replication. The prolonged arrest of ATR mutant cancer cells did not involve the
      ataxia telangiectasia mutated-dependent S-phase checkpoint, but rather closely
      resembled a previously characterized form of cell cycle arrest termed S-phase
      stasis. As ATR strongly contributed to clonogenic survival after IR treatment,
      these data suggest that blocking ATR activity might be a useful strategy for
      inducing S-phase stasis and promoting the radiosensitization of checkpoint
      deficient cancer cells.

PMID- 17043641
TI  - Regulation of clustered gene expression by cofactor of BRCA1 (COBRA1) in breast
      cancer cells.
AB  - Eucaryotic genes that are coordinately expressed tend to be clustered.
      Furthermore, gene clusters across chromosomal regions are often upregulated in
      various tumors. However, relatively little is known about how gene clusters are
      coordinately expressed in physiological or pathological conditions. Cofactor of
      BRCA1 (COBRA1), a subunit of the human negative elongation factor, has been shown
      to repress estrogen-stimulated transcription of trefoil factor 1 (TFF1 or pS2) by
      stalling RNA polymerase II. Here, we carried out a genome-wide study to identify
      additional physiological target genes of COBRA1 in breast cancer cells. The study
      identified a total of 134 genes that were either activated or repressed upon
      small hairpin RNA-mediated reduction of COBRA1. Interestingly, many COBRA1
      regulated genes reside as clusters on the chromosomes and have been previously
      implicated in cancer development. Detailed examination of two such clusters on
      chromosome 21 (21q22) and chromosome X (Xp11) reveals that COBRA1 is physically
      associated with a subset of its regulated genes in each cluster. In addition,
      COBRA1 was shown to regulate both estrogen-dependent and -independent
      transcription of the gene cluster at 21q22, which encompasses the previously
      identified COBRA1-regulated TFF1 (pS2) locus. Thus, COBRA1 plays a critical role
      in the regulation of clustered gene expression at preferred chromosomal domains
      in breast cancer cells.

PMID- 17043642
TI  - P53 in blind subterranean mole rats--loss-of-function versus gain-of-function
      activities on newly cloned Spalax target genes.
AB  - A tumor suppressor gene, p53, controls cellular responses to a variety of stress
      conditions, including DNA damage and hypoxia, leading to growth arrest and/or
      apoptosis. Recently, we demonstrated that in blind subterranean mole rats,
      Spalax, a model organism for hypoxia tolerance, the p53 DNA-binding domain
      contains a specific Arg174Lys amino acid substitution. This substitution reduces
      the p53 effect on the transcription of apoptosis genes (apaf1, puma, pten and
      noxa) and enhances it on human cell cycle arrest and p53
      stabilization/homeostasis genes (mdm2, pten, p21 and cycG). In the current study,
      we cloned Spalax apaf1 promoter and mdm2 intronic regions containing consensus
      p53-responsive elements. We compared the Spalax-responsive elements to those of
      human, mouse and rat and investigated the transcriptional activity of Spalax and
      human Arg174Lys-mutated p53 on target genes of both species. Spalax and human
      mutated p53 lost induction of apaf1 transcription, and increased induction of
      mdm2 transcription. We conclude that Spalax evolved hypoxia-adaptive mechanisms,
      analogous to the alterations acquired by cancer cells during tumor development,
      with a bias against apoptosis while favoring cell arrest and DNA repair.

PMID- 17043643
TI  - Inhibition of NEMO, the regulatory subunit of the IKK complex, induces apoptosis
      in high-risk myelodysplastic syndrome and acute myeloid leukemia.
AB  - In high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML),
      blasts constitutively activate the antiapoptotic transcription factor nuclear
      factor-kappaB (NF-kappaB). Here, we show that this NF-kappaB activation relies on
      the constitutive activation of the IkappaB kinase (IKK) complex, which is formed
      by the IKKalpha, IKKbeta and IKKgamma/NF-kappaB essential modulator (NEMO)
      subunits. A cell-permeable peptide that mimics the leucine zipper subdomain of
      IKKgamma, thus preventing its oligomerization, inhibited the constitutive NF
      kappaB activation and induced apoptotic cell death in a panel of human MDS and
      AML cell lines (P39, MOLM13, THP1 and MV4-11). Small interfering RNA-mediated
      knockdown of the p65 NF-kappaB subunit or the three IKK subunits including
      IKKgamma/NEMO also induced apoptotic cell death in P39 cells. Cell death induced
      by the IKKgamma/NEMO-antagonistic peptide involved the caspase-independent loss
      of the mitochondrial transmembrane potential as well as signs of outer
      mitochondrial membrane permeabilization with the consequent release of cytochrome
      c, apoptosis-inducing factor and endonuclease G. Primary bone marrow CD34(+)
      cells from high-risk MDS and AML patients also succumbed to the IKKgamma/NEMO
      antagonistic peptide, but not to a mutated control peptide. Altogether, these
      data indicate that malignant cells in high-risk MDS and AML cells critically
      depend on IKKgamma/NEMO to survive. Moreover, our data delineate a novel
      procedure for their therapeutic removal, through inhibition of IKKgamma/NEMO
      oligomerization.

PMID- 17043644
TI  - Pharmacologic inhibition of epigenetic modifications, coupled with gene
      expression profiling, reveals novel targets of aberrant DNA methylation and
      histone deacetylation in lung cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths in the United States
      due, in large part, to the lack of early detection methods. Lung cancer arises
      from a complex series of genetic and epigenetic changes leading to uncontrolled
      cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as
      DNA methylation and histone acetylation, are reversible with currently available
      pharmaceuticals and are early events in lung tumorigenesis detectable by non
      invasive methods. In order to better understand how epigenetic changes contribute
      to lung cancer, and to identify new disease biomarkers, we combined pharmacologic
      inhibition of DNA methylation and histone deacetylation in non-small cell lung
      cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more
      than 200 genes upregulated by these treatments, three of these, neuronatin,
      metallothionein 3 and cystatin E/M, were frequently hypermethylated and
      transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly,
      four other genes, cylindromatosis, CD9, activating transcription factor 3 and
      oxytocin receptor, were dominantly regulated by histone deacetylation and were
      also frequently downregulated in lung tumors. The majority of these genes also
      suppressed NSCLC growth in culture when ectopically expressed. This study
      therefore reveals new putative NSCLC growth regulatory genes and epigenetic
      disease biomarkers that may enhance early detection strategies and serve as
      therapeutic targets.

PMID- 17043645
TI  - Specific hypermethylation of LINE-1 elements during abnormal overgrowth and
      differentiation of human placenta.
AB  - In human post-natal somatic cells, low global levels of DNA methylation have been
      associated with the hypomethylation of several repetitive elements, a feature
      that has been proposed to be a surrogate epigenetic marker. These data, mainly
      derived from the analysis of cancer cells, suggest a potential association
      between loss of cell-growth control and altered differentiation with
      hypomethylation of repetitive sequences. Partial hydatidiform moles (PHMs) can be
      used as an alternative model for investigating this association in a non
      tumorigenic context. This gestational disease is characterized by abnormal
      overgrowth and differentiation of the placenta and spontaneous abortion. Here, we
      comprehensively analyse the DNA methylation of these trophoblastic tissues in
      both PHM and normal placenta at global and sequence-specific levels. Analysis of
      the global 5-methylcytosine content and immunohistochemistry indicate that PHM
      and normal placenta have identical global levels of DNA methylation. In contrast,
      bisulfite genomic sequencing shows that, whereas Alu, NBL2 and satellite 2
      repetitive elements are equally methylated, LINE-1 sequences are hypermethylated
      in PHM tissues ( approximately 2-fold relative to normal placenta).
      Interestingly, altered demethylation is also found in triploid diandric embryos
      that originate from dispermic fertilization of an oocyte, a common event
      responsible for most PHMs. In conclusion, alterations of DNA methylation do not
      seem to be randomly distributed in PHM, as several repeated elements remain
      unaltered, whereas LINE-1 sequences are hypermethylated. In addition, our
      findings suggest that the hypomethylation of repetitive elements in cancer is
      directly linked to the neoplasic process and not a simple consequence of loss of
      growth control observed in most of the cancer cells.

PMID- 17043646
TI  - No evidence for dual role of loss of heterozygosity in hereditary non-polyposis
      colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is caused by germline
      mutations in mismatch repair (MMR) genes, mostly MLH1 and MSH2. Somatic
      inactivation of the wild-type allele of the respective MMR gene is required for
      tumor development. Unexpectedly, a recent study utilizing DNA from paraffin
      embedded tissue material detected frequent loss of the mutant MMR gene allele in
      HNPCC tumors. Dual role for loss of heterozygosity (LOH) was proposed. If somatic
      loss of the wild-type MMR gene allele had occurred through point mutation or
      promoter hypermethylation, frequent somatic deletions at the region of the MMR
      gene locus, perhaps targeting other relevant cancer genes, could quite commonly
      lead to loss of the mutant allele. To test this hypothesis, we studied a
      population-based series of 25 fresh-frozen HNPCC tumors with a germline mutation
      in MLH1 or MSH2 for LOH. Fourteen of the 25 tumors (56%) showed LOH at the
      respective locus, and all 14 losses targeted the wild-type allele (P=0.00006).
      These results strongly support the traditional two-hit model of HNPCC gene
      inactivation.

PMID- 17043647
TI  - Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by
      interfering with Ku-DNA binding and by modulating Ku86 expression via a p38
      kinase-dependent mechanism.
AB  - Ionizing radiation exposure results in the activation of several tyrosine kinase
      receptors that participate in radiation-induced DNA damage response and
      radioresistance. We previously showed that insulin-like growth factor 1 receptor
      (IGF-1R) inhibition enhanced radiosensitivity of non-small-cell lung cancer
      (NSCLC) cells. In this paper, we demonstrate that in U1810 NSCLC cells gamma
      radiation activates IGF-1R within 10 min, with a maximal activation effect 2 h
      post-irradiation. Impairment of IGF-1R tyrosine kinase activity enhances human
      lung cancer cells radiosensitivity by a mechanism that involves
      phosphatidylinositol 3-kinase (PI3-K) and p38 kinase. In an active form, IGF-1R
      binds and activates p38 kinase, promoting receptor signaling. Conversely,
      inhibition of IGF-1R phosphorylation results in IGF-1R/p38 complex disruption and
      p38 kinase inactivation. We have also demonstrated that in insulin-like growth
      factor-1-stimulated cells, Ku-DNA-binding activation is induced by ionizing
      radiation within 4 h, reaches a maximum level at 12 h and remains active up to 72
      h. Blockade of IGF-1R activity or its downstream signaling through p38 kinase
      induces a decrease in radiation-mediated Ku-DNA-binding activation and
      downregulates the level of Ku86, without affecting Ku70 expression in the nucleus
      of U1810 cells. The IGF-1R signaling via PI3-K does not interfere with the p38
      signaling, the Ku-DNA-binding activity or the level of Ku86. Our present study
      demonstrates for the first time that ionizing radiation activates IGF-1R.
      Inhibition of IGF-1R signaling via p38 kinase induces radiosensitivity by a novel
      mechanism involving nuclear Ku86.

PMID- 17043648
TI  - Tissue transglutaminase expression promotes cell attachment, invasion and
      survival in breast cancer cells.
AB  - Distant metastasis is frequently observed in patients with breast cancer and is a
      major cause of cancer-related deaths in these patients. Currently, very little is
      known about the mechanisms that underlie the development of the metastatic
      phenotype in breast cancer cells. We previously found that metastatic breast
      cancer cells express high levels of tissue transglutaminase (TG2), but
      established no direct link between TG2 and metastasis. In this study, we
      hypothesized that TG2 plays a role in conferring the metastatic phenotype to
      breast cancer cells. The results obtained suggested that increased expression of
      TG2 in breast cancer cells contributes to their increased survival, invasion and
      motility. We further found that TG2 protein in a metastatic breast cancer MDA
      MB231 cells was present on the cell surface in close association with integrins
      beta1, beta4 and beta5. Downregulation of endogenous TG2 by small interfering RNA
      inhibited fibronectin (Fn)-mediated cell attachment, survival and invasion.
      Conversely, ectopic expression of TG2 augmented invasion of breast cancer cells
      and attachment to Fn-coated surfaces. We conclude that TG2 expression in breast
      cancer cells plays an important role in the development of the metastatic
      phenotype.

PMID- 17043649
TI  - Apoptosis and erythroid differentiation triggered by Bcr-Abl inhibitors in CML
      cell lines are fully distinguishable processes that exhibit different sensitivity
      to caspase inhibition.
AB  - Imatinib targets the Bcr-Abl oncogene that causes chronic myelogenous leukemia
      (CML) in humans. Recently, we demonstrated that besides triggering apoptosis in
      K562 cells, imatinib also mediated their erythroid differentiation. Although both
      events appear to proceed concomitantly, it is not known at present whether or not
      imatinib-induced apoptosis and differentiation are interdependent processes.
      Hence, we investigated the requirements for Bcr-Abl inhibitor-mediated apoptosis
      and erythroid differentiation in several established and engineered CML cell
      lines. Imatinib triggered apoptosis and erythroid differentiation of different
      CML cell lines, but only apoptosis exhibited sensitivity to ZVAD-fmk inhibition.
      Conversely, the p38 mitogen-activated protein (MAP) kinase inhibitor, SB202190,
      significantly slowed down erythroid differentiation without affecting caspase
      activation. Furthermore, imatinib and PD166326, another Bcr-Abl inhibitory
      molecule, triggered erythroid differentiation of K562 cell clones, nevertheless
      resistant to Bcr-Abl inhibitor-induced apoptosis. Finally, short hairpin RNA
      inhibitor (shRNAi) silencing of caspase 3 efficiently inhibited caspase activity
      but had no effect on erythroid differentiation, whereas silencing of Bcr-Abl
      mimicked imatinib or PD166326 treatment, leading to increased apoptosis and
      erythroid differentiation of K562 cells. Taken together, our findings not only
      demonstrate that Bcr-Abl inhibitor-mediated apoptosis and differentiation are
      fully distinguishable events, but also that caspases are dispensable for
      erythroid differentiation of established CML cell lines.

PMID- 17043650
TI  - GSK3 beta mediates suppression of cyclin D2 expression by tumor suppressor PTEN.
AB  - PTEN, encoding a lipid phosphatase, is a tumor suppressor gene and is mutated in
      various types of cancers. It is reported to regulate G1 to S phase transition of
      the cell cycle by influencing the expression, protein stability and subcellular
      location of cyclin D1. Here, we provide evidence that PTEN modulates the
      transcription and protein stability of cyclin D2. Targeted deletion of Pten in
      mouse embryonic fibroblasts (MEFs) endowed cells with greater potential to
      overcome G1 arrest than wild-type MEFs and led to the elevated expression of
      cyclin D2, which was suppressed by the introduction of PTEN. We further defined a
      pathway involving GSK3beta and beta-catenin/TCF in PTEN-mediated suppression of
      cyclin D2 transcription. LiCl, an inhibitor of GSK3beta, abolished inhibitory
      effect of PTEN on cyclin D2 expression, and TCF members could directly bind to
      the promoter of cyclin D2 and regulate its transcription in a CREB-dependent
      manner. Our results indicate that the downregulation of cyclin D2 expression by
      PTEN is mediated by the GSK3beta/beta-catenin/TCF pathway in cooperation with
      CREB, and suggest a convergence from the PI-3 kinase/PTEN pathway and the Wnt
      pathway in modulation of cyclin D2 expression.

PMID- 17043651
TI  - A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma
      cells both in vitro and in vivo.
AB  - Signal transducer and activator of transcription-3 (STAT3) is constitutively
      activated in a variety of cancer types, including malignant gliomas. STAT3 is
      activated by phosphorylation of a tyrosine residue, after which it dimerizes and
      translocates into the nucleus. There it regulates the expression of several genes
      responsible for proliferation and survival at the transcriptional level. A
      selective inhibitor of STAT3 phosphorylation, AG490, has been shown to inhibit
      growth and induce apoptosis in some cancer cell types. However, although AG490
      routinely shows in vitro anticancer activity, it has not consistently
      demonstrated an in vivo anticancer effect in animal models. Here, we have tested
      WP1066, a novel inhibitor structurally related to AG490 but significantly more
      potent and active, against human malignant glioma U87-MG and U373-MG cells in
      vitro and in vivo. IC(50) values for WP1066 were 5.6 muM in U87-MG cells and 3.7
      muM in U373-MG cells, which represents 18-fold and eightfold increases in
      potency, respectively, over that of AG490. WP1066 activated Bax, suppressed the
      expression of c-myc, Bcl-X(L) and Mcl-1, and induced apoptosis. Systemic
      intraperitoneal administration of WP1066 in mice significantly (P<0.001)
      inhibited the growth of subcutaneous malignant glioma xenografts during the 30
      day follow-up period. Immunohistochemical analysis of the excised tumors revealed
      that phosphorylated STAT3 levels in the WP1066 treatment group remained inhibited
      at 3 weeks after the final WP1066 injection, whereas tumors from the control
      group expressed high levels of phosphorylated STAT3. We conclude that WP1066
      holds promise as a therapeutic agent against malignant gliomas.

PMID- 17043652
TI  - Tumor progression induced by the loss of E-cadherin independent of beta
      catenin/Tcf-mediated Wnt signaling.
AB  - E-cadherin-mediated cell-cell adhesion is frequently lost during the development
      of malignant epithelial cancers. Employing a transgenic mouse model of beta-cell
      carcinogenesis (Rip1Tag2) we have previously shown that the loss of E-cadherin is
      a rate-limiting step in the progression from adenoma to carcinoma. However, the
      mere loss of cell adhesion may not be sufficient and additional signals are
      required to cause tumor cells to permeate the basal membrane and to invade
      surrounding tissue. Besides being an important component of the E-cadherin cell
      adhesion complex, beta-catenin plays a critical role in canonical Wnt signaling.
      We report here that beta-catenin-mediated Wnt signaling does not contribute to
      tumor progression in Rip1Tag2 mice. E-cadherin downregulates beta-catenin/Tcf
      mediated transcriptional activity by sequestrating beta-catenin into E-cadherin
      cell-adhesion complexes even in the presence of activated Wnt signaling. Upon
      loss of E-cadherin expression, beta-catenin is degraded and Tcf/beta-catenin
      mediated transcriptional activity is not induced. Moreover, forced expression of
      constitutive-active beta-catenin or genetic ablation of Tcf/beta-catenin
      transcriptional activity in tumor cells of Rip1Tag2 transgenic mice does not
      affect tumor progression. Together, the data indicate that signals other than
      beta-catenin/Tcf-mediated Wnt signaling are induced by the loss of E-cadherin
      during tumor progression in Rip1Tag2 transgenic mice.

PMID- 17043653
TI  - AKT induces senescence in primary esophageal epithelial cells but is permissive
      for differentiation as revealed in organotypic culture.
AB  - Epidermal growth factor receptor (EGFR) overexpression and activation is critical
      in the initiation and progression of cancers, especially those of epithelial
      origin. EGFR activation is associated with the induction of divergent signal
      transduction pathways and a gamut of cellular processes; however, the cell-type
      and tissue-type specificity conferred by certain pathways remains to be
      elucidated. In the context of the esophageal epithelium, a prototype stratified
      squamous epithelium, EGFR overexpression is relevant in the earliest events of
      carcinogenesis as modeled in a three-dimensional organotypic culture system. We
      demonstrate that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway,
      and not the MEK/MAPK (mitogen-activated protein kinase) pathway, is
      preferentially activated in EGFR-mediated esophageal epithelial hyperplasia, a
      premalignant lesion. The hyperplasia was abolished with direct inhibition of PI3K
      and of AKT but not with inhibition of the MAPK pathway. With the introduction of
      an inducible AKT vector in both primary and immortalized esophageal epithelial
      cells, we find that AKT overexpression and activation is permissive for complete
      epithelial formation in organotypic culture, but imposes a growth constraint in
      cells grown in monolayer. In organotypic culture, AKT mediates changes related to
      cell shape and size with an expansion of the differentiated compartment.

PMID- 17043654
TI  - The tumour-suppressor Scribble dictates cell polarity during directed epithelial
      migration: regulation of Rho GTPase recruitment to the leading edge.
AB  - Altered expression of human Scribble is associated with invasive epithelial
      cancers, however, its role in tumour development remains unclear. Mutations in
      Drosophila Scribble result in loss of polarity, overproliferation and 3D
      tumourous overgrowth of epithelial cells. Using complementation studies in
      Drosophila we recently demonstrated that expression of human Scribble can also
      regulate polarity and restrict tissue overgrowth. Here, we have undertaken a
      detailed study of human Scribble function in the polarized mammary cell line,
      MCF10A. We show that although Scribble does not seem to be required for apical
      basal polarity or proliferation control in MCF10A cells, Scribble is essential
      for the control of polarity associated with directed epithelial cell migration.
      Scribble-depleted MCF10A cells show defective in vitro wound closure and
      chemotactic movement. The cells at the wound edge fail to polarize, show reduced
      lamellipodia formation and impaired recruitment of Cdc42 and Rac1 to the leading
      edge. Furthermore, we show that this function is relevant in vivo as Scribble
      mutant mice show defective epidermal wound healing. This data identifies an
      essential role for mammalian Scribble in the regulation of the polarity
      specifically involved in directed epithelial migration.

PMID- 17043655
TI  - Collagen type I-induced Smad-interacting protein 1 expression downregulates E
      cadherin in pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease with poor prognosis. Production of
      large quantities of extracellular matrix and early metastasis are characteristics
      of this disease. One important step in the development of various cancers is the
      loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell
      cell adhesion. It has been shown that collagen type I promotes downregulation of
      E-cadherin expression, which correlates with enhanced cell migration and
      invasiveness. In this context, we elucidated the role of Smad-interacting protein
      1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene
      expression. We demonstrate that SIP1 upregulation shows an inverse relationship
      with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1
      expression can be induced by exposure to collagen type I in a src-dependent
      manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein
      levels. Taken together, these results suggest that SIP1 is involved in the
      progression of pancreatic cancer and plays a role in mediating signal
      transduction from collagen type I to downregulate E-cadherin expression.

PMID- 17043656
TI  - The p85 regulatory subunit of PI3K mediates TSH-cAMP-PKA growth and survival
      signals.
AB  - Phosphatidylinositol 3-kinase (PI3K) is necessary for thyroid stimulating hormone
      (TSH)-induced cell cycle progression. To determine the molecular mechanism
      linking PI3K to TSH, we have identified a serine residue in p85alpha(PI3K)
      phosphorylated by protein kinase A (PKA) in vitro and in vivo. Expression of an
      alanine mutant (p85A) abolished cyclic AMP/TSH-induced cell cycle progression and
      was lethal in thyroid cells (FRTL-5). The aspartic version of the p85alpha(PI3K)
      (p85D) inhibited apoptosis following TSH withdrawal. The p85alpha(PI3K) wild type
      not the p85A bound PKA regulatory subunit RIIbeta in cells stimulated with cAMP
      or TSH. The binding of the aspartic version of p85alpha(PI3K) to RIIbeta was
      independent of cAMP or TSH stimulation. Similarly, binding of PI3K to p21Ras and
      activation of AKT, a downstream PI3K target, were severely impaired in cells
      expressing the p85A mutant. Finally, we found that the catalytic activity of PI3K
      was stimulated by TSH in cells expressing the wild-type p85alpha(PI3K) but not in
      cells expressing p85A. This latter mutant did not affect the epidermal growth
      factor-stimulated PI3K activity. We suggest that (1) TSH-cAMP-induced PKA
      phosphorylates p85alpha(PI3K) at serine 83, (2) phosphorylated p85alpha(PI3K)
      binds RIIbeta-PKA and targets PKAII to the membrane, and (3) PI3K activity and
      p21Ras binding to PI3K increase and activate PI3K downstream targets. This
      pathway is essential for the transmission of TSH-cAMP growth signals.

PMID- 17043657
TI  - Periostin promotes invasiveness and resistance of pancreatic cancer cells to
      hypoxia-induced cell death: role of the beta4 integrin and the PI3k pathway.
AB  - Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a
      rapid progression and poor treatment response. Using gene expression profiling of
      pancreatic cancer tissues, we previously identified periostin as a potential
      diagnostic and therapeutic target. In this study, we report the overexpression of
      periostin in a larger set of pancreatic cancer tissues and show that although the
      periostin transcript is exclusively expressed in tumour cells, the protein
      product is only detected in the extracellular matrix adjacent to cancer cells.
      Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly
      increased levels of periostin in the sera of pancreatic cancer patients compared
      to non-cancer controls. We demonstrate that periostin promotes the invasiveness
      of tumour cells by increasing the motility of cells without inducing expression
      of proteases, and enhances the survival of tumour cells exposed to hypoxic
      conditions. At the molecular level, we provide evidence that the alpha(6)beta(4)
      integrin complex acts as the cell receptor of periostin in pancreatic cancer
      cells and that interaction promotes phosphorylation of focal adhesion kinase
      (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but
      not the RAS/MEK/ERK pathway. These findings suggest an important role of
      periostin in pancreatic cancer and provide a rationale to study periostin for
      diagnostic and therapeutic applications.

PMID- 17043658
TI  - Role of hypoxia inducible factor-1 alpha in modulation of apoptosis resistance.
AB  - Hypoxia inducible factor-1 (HIF-1) is the major transcription factor and key
      regulator of adoptive responses to hypoxia. Although it usually promotes tumor
      cell survival under hypoxia, it has also been implied to trigger apoptosis.
      Although the impact of hypoxia has been extensively studied in many adult solid
      tumors, its role in most childhood tumors, for example, in rhabdomyosarcoma (RMS)
      or Ewing sarcoma (ES), has not yet been addressed. Here, we report that hypoxia
      protects A204 RMS and A673 ES cells against anticancer drug- or tumor necrosis
      factor-related apoptosis-inducing ligand-induced apoptosis and that Hif-1alpha
      plays a key role in conferring apoptosis resistance under hypoxia. Although a
      functional HIF-1 pathway and proapoptotic proteins such as p53 and Bcl-2/E1B 19
      kDa interacting protein 3 were activated under hypoxia in both A204 RMS and A673
      ES cells, these cells remained refractory to apoptosis. Concomitant analysis of
      antiapoptotic proteins revealed that hypoxia induced expression of Bcl-2 and
      inhibitor of apoptosis proteins (IAP)-2 as well as proteins associated with
      anaerobic metabolism such as the glucose transporter protein GLUT-1 and the
      glycolytic enzyme Aldolase A. Specific downregulation of Hif-1alpha by RNA
      interference significantly enhanced apoptosis under hypoxia by preventing the
      hypoxia-mediated increase in GLUT-1 expression without altering expression levels
      of the antiapoptotic proteins Bcl-2 or cIAP-2. Moreover, glucose deprivation
      induced apoptosis of A204 RMS and A673 ES cells was inhibited under hypoxic
      conditions in a Hif-1alpha-dependent manner. As GLUT-1 was induced via Hif-1alpha
      under hypoxia in A204 RMS and A673 ES, these findings suggest that the Hif-1alpha
      mediated increase in glucose uptake plays an important role in conferring
      apoptosis resistance. Thus, hypoxia-inducible genes may represent novel targets
      for therapeutic intervention in some pediatric tumors, which warrants further
      investigation.

PMID- 17043659
TI  - E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate
      carcinoma.
AB  - The retinoblastoma (pRB) family proteins regulate the E2F transcription factors;
      their complexes regulate critical transitions through the cell cycle. The
      function of these pRB family/E2F complexes, which includes p130/E2F4, in response
      to genotoxic agents, is not well understood. We investigated the role of E2F4 in
      the genotoxic stress response. Following radiation treatment, E2F4 colocalized
      with p130 in the nucleus during a radiation-induced stable G(2)-phase arrest.
      Arrested cells had significantly decreased expression of Cyclins A2 and B1 and
      decreased phosphorylation of mitotic protein monoclonal-2 (MPM-2) mitotic
      proteins. Small interference RNA (siRNA)-mediated knockdown of E2F4 sensitized
      cells to subsequent irradiation, resulting in enhanced cellular DNA damage and
      cell death, as determined by caspase activation and decreased clonogenic cell
      survival. Downstream E2F4 targets potentially involved in the progression from
      G(2) into M phase were identified by oligonucleotide microarray expression
      profiling. Chromatin immunoprecipitation localized E2F4 at promoter regions of
      the Bub3 and Pttg1 mitotic genes following irradiation, which were among the
      downregulated genes identified by the microarray. These data suggest that in
      response to radiation, E2F4 becomes active in the nucleus, enforces a stable G(2)
      arrest by target gene repression, and thus provides increased cell survival
      ability by minimizing propagation of cells that have irreparable DNA damage.

PMID- 17043660
TI  - Snail silencing effectively suppresses tumour growth and invasiveness.
AB  - The transcription factor Snail has been recently proposed as an important
      mediator of tumour invasion because of its role in downregulation of E-cadherin
      and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led
      to the consideration of Snail as a potential therapeutic target to block tumour
      progression. In this report, we provide evidence for this hypothesis. We show
      that silencing of Snail by stable RNA interference in MDCK-Snail cells induces a
      complete mesenchymal to epithelial transition (MET), associated to the
      upregulation of E-cadherin, downregulation of mesenchymal markers and inhibition
      of invasion. More importantly, stable interference of endogenous Snail in two
      independent carcinoma cell lines leads to a dramatic reduction of in vivo tumour
      growth, accompanied by increased tumour differentiation and a significant
      decrease in the expression of MMP-9 and angiogenic markers and invasiveness.
      These results indicate that use of RNA interference can be an effective tool for
      blocking Snail function, opening the way for its application in new antiinvasive
      therapies.

PMID- 17043661
TI  - A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2
      activity, cell cycle arrest and tumor growth reduction in vivo.
AB  - One strategy in the development of anticancer therapeutics has been to arrest
      malignant proliferation through inhibition of the enzymatic activity of cyclin
      dependent kinases (cdks), which are key regulatory molecules of the cell cycle.
      Over the past few years, numerous compounds with remarkable cdk inhibitory
      activity have been studied in cancer therapy, although it is very difficult to
      point out the best cdk to target. An excellent candidate appears to be cdk2,
      whose alteration is a pathogenic hallmark of tumorigenesis. The small molecule
      described in our study showed an inhibitory effect on the kinase activity of
      cdk2, a significant growth arrest observed in a colony formation assay and a
      reduction in the size of the tumor in nude mice, thus suggesting its potential
      role as a promising new type of mechanism-based antitumor drug, also for the
      treatment of hyperproliferative disorders.

PMID- 17043662
TI  - Identification of molecular markers and signaling pathway in endometrial cancer
      in Hong Kong Chinese women by genome-wide gene expression profiling.
AB  - Endometrial cancer is the third most common gynecologic malignancy and the ninth
      most common malignancy for females overall in Hong Kong. Approximately 80% or
      more of these cancers are endometrioid endometrial adenocarcinomas. The aim of
      this study was to reveal genes contributing to the development of endometrioid
      endometrial cancer, which may impact diagnosis, prognosis and treatment of the
      disease. Whole-genome gene expression analysis was completed for a set of 55
      microdissected sporadic endometrioid endometrial adenocarcinomas and 29
      microdissected normal endometrium specimens using the Affymetrix Human U133 Plus
      2.0 oligonucleotide microarray. Selected genes of interest were validated by
      quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was
      performed to reveal gene interactions involved in endometrial tumorigenesis.
      Unsupervised hierarchical clustering displayed a distinct separation between the
      endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis
      identified 117 highly differentially regulated genes (>or=4.0-fold change), which
      distinguished the endometrial cancer specimens from normal endometrium. Twelve
      novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5,
      BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and
      further validated in an independent set of 56 cancer and 29 normal samples using
      qRT-PCR. In addition, 10 genes were differentially regulated in late-stage
      cancer, as compared to early-stage disease, and may be involved in tumor
      progression. Pathway analysis of the expression data from this tumor revealed an
      interconnected network consisting of 21 aberrantly regulated genes involved in
      angiogenesis, cell proliferation and chromosomal instability. The results of this
      study highlight the molecular features of endometrioid endometrial cancer and
      provide insight into the events underlying the development and progression of
      endometrioid endometrial cancer.

PMID- 17043663
TI  - Proteomic identification of the wt-p53-regulated tumor cell secretome.
AB  - Tumor-stroma interactions play a major role in tumor development, maintenance and
      progression. Yet little is known on how the genetic alterations that underlie
      cell transformation elicit cell extrinsic changes modulating heterotypic cell
      interactions. We hypothesized that these events involve a modification in the
      complement of secreted proteins by the cell, acting as mediators of intercellular
      communication. To test this hypothesis, we examined the role of wt-p53, a major
      tumor suppressor, on the tumor microenvironment through its regulation of
      secreted factors. Using a combination of 2-DE and cICAT proteomic techniques, we
      found a total of 111 secreted proteins, 39 of which showed enhanced and 21
      inhibited secretion in response to wt-p53 expression. The majority of these were
      not direct targets of p53 transcription factor activity, suggesting a novel role
      for wt-p53 in the control of intracellular protein trafficking and/or secreted
      protein stability. Evidence for p53-controlled post-translational modifications
      on nine secreted proteins was also found. These findings will enhance our
      understanding of wt-p53 modulated interactions of the tumor with its environment.

PMID- 17043664
TI  - Expression and localization of PDGF-B, PDGF-D, and PDGF receptor in the kidney of
      angiotensin II-infused rat.
AB  - Lipid accumulation in the kidney is a marker of tissue damage and may play a role
      in the development of renal injury. We have previously shown that long-term
      administration of angiotensin II in rats causes increased expression of
      transforming growth factor-beta1, coupled with an accumulation of lipids in the
      tubular and vascular wall cells in the kidney. In this study, we examine the
      regulation of expression of platelet-derived growth factor (PDGF) and its
      receptor system and their co-localization with lipid deposits in the kidneys of
      angiotensin II-infused rats. Real-time RT-PCR showed that expression of PDGF-B,
      PDGF-D, and PDGF receptor-beta (PDGFR-beta) mRNA was increased by angiotensin II
      infusion, and in situ hybridization showed the co-localization of these mRNAs.
      Tubular cells that had increased PDGF-B mRNA expression were positive for lipid
      deposition and also for cellular proliferation, which was indicated by the
      presence of proliferating cell nuclear antigen. By contrast, in the kidneys of
      angiotensin II-infused rats, apoptosis occurred in tubular cells that contained
      deposits of iron but not lipids. The deposition of lipids and upregulation of
      PDGF-B, PDGF-D, and PDGFR-beta induced by administration of angiotensin II were
      all suppressed by the selective angiotensin II type 1 (AT(1)) receptor antagonist
      losartan, but not by the nonspecific vasodilator hydralazine. The findings that
      lipid accumulation, upregulation of PDGF-B, PDGF-D, and PDGFR-beta, and cellular
      proliferation were topologically associated and regulated in an AT(1) receptor
      dependent manner in the kidney of angiotensin II-infused rats suggests that these
      phenomena are related.

PMID- 17043665
TI  - DNA methylation-dependent silencing of CST6 in human breast cancer cell lines.
AB  - Cystatin M (CST6) is a candidate breast cancer tumor suppressor that is expressed
      in normal and premalignant breast epithelium, but not in metastatic breast cancer
      cell lines. CST6 is subject to epigenetic silencing in MCF-7 breast cancer cells
      related to methylation of the CpG island that encompasses the CST6 proximal
      promoter region and exon 1. In the current study, CST6 CpG island methylation and
      expression status was examined in a panel of breast cancer cell lines. Seven of
      12 (58%) cell lines lack detectable expression of CST6 and treatment of these
      cells with 5-aza-2'-deoxycytidine resulted in a significant increase in CST6
      expression, suggesting that the loss of expression may be related to methylation
      dependent epigenetic silencing. Bisulfite sequencing of CST6 in a subset of
      breast cancer cell lines revealed CpG island hypermethylation in CST6-negative
      cells, and an absence of CpG island methylation in cells that express CST6. The
      extent of regional methylation was strongly associated with the lack of
      expression of CST6 among these cell lines. In particular, hypermethylation of the
      proximal promoter was significantly associated with CST6 gene silencing, and
      methylation of a number of individual CpGs was found to be statistically
      correlated with extinction of gene expression. These results establish a strong
      link between CST6 promoter hypermethylation and loss of CST6 expression in breast
      cancer cell lines, and suggest that methylation-dependent epigenetic silencing of
      CST6 may represent an important mechanism for loss of CST6 during breast
      carcinogenesis in vivo.

PMID- 17043666
TI  - Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from
      sustained distension of the urinary bladder.
AB  - Urinary bladder outlet obstruction results in sustained stretch of the detrusor
      muscle and can lead to pathological smooth muscle hyperplasia and hypertrophy.
      The epidermal growth factor receptor (EGFR) is a cognate receptor for mitogens
      implicated in bladder hyperplasia/hypertrophy. Here, we investigated the
      potential for modulation of this pathway by pharmacologic targeting with a
      clinically available EGFR antagonist using an organ culture model of bladder
      stretch injury as a test system. Urinary bladders from adult female rats were
      distended in vivo with medium containing the EGFR inhibitor ZD1839 (gefitinib,
      Iressa). The bladders were excised and incubated in ex vivo organ culture for 4
      24 h. EGFR phosphorylation, DNA proliferation, and the extent of apoptosis in the
      cultured tissues were assessed. To verify that the smooth muscle cells (SMC) are
      a target of the EGFR inhibitor, primary culture human and rat bladder SMC were
      subjected to cyclic mechanical stretch in vitro in the presence of ZD1839. Levels
      of phosphorylated EGFR were significantly increased in the detrusor muscle with
      12 h of stretch in the organ cultures. This activation coincided with a
      subsequent 23-fold increase in DNA synthesis and a 30-fold decrease in apoptosis
      in the muscle compartment at 24 h. In the presence of ZD1839, DNA synthesis was
      reduced to basal levels without an increase in the rate of apoptosis under ex
      vivo conditions. Mechanical stretch of bladder SMC in vitro resulted in a
      significant increase in DNA synthesis, which was completely abrogated by
      treatment with ZD1839 but not by AG825, an inhibitor of the related receptor,
      ErbB2. Our results indicate that the EGFR pathway is a physiologically relevant
      signaling mechanism in hypertrophic bladder disease resulting from mechanical
      distension and may be amenable to pharmacologic intervention.

PMID- 17043667
TI  - Comparison of lymphoblast mitochondria from normal subjects and patients with
      Barth syndrome using electron microscopic tomography.
AB  - Barth syndrome (BTHS) is a mitochondrial disorder that is caused by mutations in
      the tafazzin gene, which affects phospholipid composition. To determine whether
      this defect leads to alterations in the internal three-dimensional organization
      of mitochondrial membranes, we applied electron microscopic tomography to
      lymphoblast mitochondria from BTHS patients and controls. Tomograms were formed
      from 50 and 150 nm sections of chemically fixed lymphoblasts and the data were
      used to manually segment volumes of relevant structural details. Normal
      lymphoblast mitochondria contained well-aligned, lamellar cristae with slot-like
      junctions to the inner boundary membrane. In BTHS, mitochondrial size was more
      variable and the total mitochondrial volume per cell increased mainly due to
      clusters of fragmented mitochondria inside nuclear invaginations. However,
      mitochondria showed reduced cristae density, less cristae alignment, and
      inhomogeneous cristae distribution. Three-dimensional reconstruction of BTHS
      mitochondria revealed zones of adhesion of the opposing inner membranes, causing
      obliteration of the intracrista space. We found small isolated patches of
      adhesion as well as extended adhesion zones, resulting in sheets of collapsed
      cristae packaged in multiple concentric layers. We also found large tubular
      structures (diameter 30-150 nm) that appeared to be derivatives of the adhesion
      zones. The data suggest that mitochondrial abnormalities of BTHS involve
      adhesions of inner mitochondrial membranes with subsequent collapse of the
      intracristae space.

PMID- 17043669
TI  - In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a
      GABAergic mechanism.
AB  - BACKGROUND AND PURPOSE: Recent evidence suggests that 5-HT(2C) receptor
      activation may inhibit midbrain 5-HT neurones by activating neighbouring GABA
      neurones. This hypothesis was tested using the putative selective 5-HT(2C)
      receptor agonist, WAY 161503. EXPERIMENTAL APPROACH: The effect of WAY 161503 on
      5-HT cell firing in the dorsal raphe nucleus (DRN) was investigated in
      anaesthetised rats using single unit extracellular recordings. The effect of WAY
      161503 on DRN GABA neurones was investigated using double label
      immunohistochemical measurements of Fos, glutamate decarboxylase (GAD) and 5
      HT(2C) receptors. Finally, drug occupancy at 5-HT(2A) receptors was investigated
      using rat positron emission tomography and ex vivo binding studies with the 5
      HT(2A) receptor radioligand [(11)C]MDL 100907. KEY RESULTS: WAY 161503 caused a
      dose-related inhibition of 5-HT cell firing which was reversed by the 5-HT(2)
      receptor antagonist ritanserin and the 5-HT(2C) receptor antagonist SB 242084 but
      not by the 5-HT(1A) receptor antagonist WAY 100635. SB 242084 pretreatment also
      prevented the response to WAY 161503. The blocking effects of SB 242084 likely
      involved 5-HT(2C) receptors because the drug did not demonstrate 5-HT(2A)
      receptor occupancy in vivo or ex vivo. The inhibition of 5-HT cell firing induced
      by WAY 161503 was partially reversed by the GABA(A) receptor antagonist
      picrotoxin. Also, WAY 161503 increased Fos expression in GAD positive DRN
      neurones and DRN GAD positive neurones expressed 5-HT(2C) receptor
      immunoreactivity. CONCLUSIONS AND IMPLICATIONS: These findings indicate that WAY
      161503 inhibits 5-HT cell firing in the DRN in vivo, and support a mechanism
      involving 5-HT(2C) receptor-mediated activation of DRN GABA neurones.

PMID- 17043670
TI  - The MC4 receptor and control of appetite.
AB  - Mutations in the human melanocortin (MC)4 receptor have been associated with
      obesity, which underscores the relevance of this receptor as a drug target to
      treat obesity. Infusion of MC4R agonists decreases food intake, whereas
      inhibition of MC receptor activity by infusion of an MC receptor antagonist or
      with the inverse agonist AgRP results in increased food intake. This review
      addresses the role of the MC system in different aspects of feeding behaviour.
      MC4R activity affects meal size and meal choice, but not meal frequency, and the
      type of diet affects the efficacy of MC4R agonists to reduce food intake. The
      central sites involved in the different aspects of feeding behaviour that are
      affected by MC4R signalling are being unravelled. The paraventricular nucleus
      plays an important role in food intake per se, whereas MC signalling in the
      lateral hypothalamus is associated with the response to a high fat diet. MC4R
      signalling in the brainstem has been shown to affect meal size. Further genetic,
      behavioural and brain-region specific studies need to clarify how the MC4R
      agonists affect feeding behaviour in order to determine which obese individuals
      would benefit most from treatment with these drugs. Application of MCR agonists
      in humans has already revealed side effects, such as penile erections, which may
      complicate introduction of these drugs in the treatment of obesity.

PMID- 17043672
TI  - Characterization of the snake venom ligand [125I]-DNP binding to natriuretic
      peptide receptor-A in human artery and potent DNP mediated vasodilatation.
AB  - BACKGROUND AND PURPOSE: The natriuretic peptides, ANP and BNP, modulate vascular
      smooth muscle tone in human conduit arteries. Surprisingly, the natriuretic
      peptide receptor-A (NPR-A) has not been visualized using radioligand binding in
      these vessels. A new member of this peptide family, Dendroaspis natriuretic
      peptide (DNP) identified from snake venom, has been proposed to be present in
      human plasma and endothelial cells. Also, recently a novel radioligand, [(125)I]
      DNP, has been characterized as selective for NPR-A in human heart. EXPERIMENTAL
      APPROACH: Our aims were to investigate expression and function of NPR-A receptors
      in human mammary artery using [(125)I]-DNP to quantify receptor density,
      immunocytochemistry to delineate the cellular distribution of the receptor and in
      vitro pharmacology to compare DNP induced vasodilatation to that of ANP. KEY
      RESULTS: Saturable, sub-nanomolar affinity [(125)I]-DNP binding was detected to
      smooth muscle of mammary artery, with receptor density of approximately 2 fmol
      mg(-1) protein, comparable to that of other vasoactive peptides. NPR-A
      immunoreactivity was localised to vascular smooth muscle cells and this was
      confirmed with fluorescence dual labelling. NPR-A expression was not detected in
      the endothelium. Like ANP, DNP fully reversed the constrictor response to ET-1 in
      endothelium intact or denuded mammary artery, with comparable nanomolar
      potencies. CONCLUSIONS AND IMPLICATIONS: This is the first characterization of
      NPR-A in human mammary artery using [(125)I]-DNP and we provide evidence for the
      presence of receptor protein on vascular smooth muscle cells, but not endothelial
      cells. This implies that the observed vasodilatation is predominantly mediated
      via direct activation of smooth muscle NPR-A.

PMID- 17043671
TI  - Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB(1) and
      VR(1) receptors.
AB  - BACKGROUND AND PURPOSE: Hyperdynamic circulation and mesenteric hyperaemia are
      found in cirrhosis. To delineate the role of endocannabinoids in these changes,
      we examined the cardiovascular effects of anandamide, AM251 (CB(1) antagonist),
      AM630 (CB(2) antagonist) and capsazepine (VR1 antagonist), in a rat model of
      cirrhosis. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation.
      Controls underwent sham operation. Four weeks later, diameters of mesenteric
      arteriole and venule (intravital microscopy), arterial pressure, cardiac output,
      systemic vascular resistance and superior mesenteric artery (SMA) flow were
      measured after anandamide, AM251 (with or without anandamide), AM630 and
      capsazepine administration. CB(1), CB(2) and VR1 receptor expression in SMA was
      assessed by western blot and RT-PCR. KEY RESULTS: Anandamide increased mesenteric
      vessel diameter and flow, and cardiac output in cirrhotic rats, but did not
      affect controls. Anandamide induced a triphasic arterial pressure response in
      controls, but this pattern differed markedly in cirrhotic rats. Pre
      administration of AM251 blocked the effects of anandamide. AM251 (without
      anandamide) increased arterial pressure and systemic vascular resistance,
      constricted mesenteric arterioles, decreased SMA flow and changed cardiac output
      in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac
      output and mesenteric arteriolar diameter and flow, and increased systemic
      vascular resistance in cirrhotic rats, but lacked effect in controls. Expression
      of CB(1) and VR1 receptor proteins were increased in cirrhotic rats. AM630 did
      not affect any cardiovascular parameter in either group. CONCLUSIONS AND
      IMPLICATIONS: These data suggest that endocannabinoids contribute to hyperdynamic
      circulation and mesenteric hyperaemia in cirrhosis, via CB(1)- and VR1-mediated
      mechanisms.

PMID- 17043673
TI  - Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the
      mitochondrial K(ATP) channel conferring cardioprotection against hypoxic injury.
AB  - BACKGROUND AND PURPOSE: Diazoxide, a well-known opener of the mitochondrial ATP
      sensitive potassium (mitoK(ATP)) channel, has been demonstrated to exert
      cardioprotective effect against ischemic injury through the mitoK(ATP) channel
      and protein kinase C (PKC). We aimed to clarify the role of PKC isoforms and the
      relationship between the PKC isoforms and the mitoK(ATP) channel in diazoxide
      induced cardioprotection. EXPERIMENTAL APPROACH: In H9c2 cells and neonatal rat
      cardiomyocytes, PKC-epsilon activation was examined by Western blotting and
      kinase assay. Flavoprotein fluorescence, mitochondrial Ca(2+) and mitochondrial
      membrane potential were measured by confocal microscopy. Cell death was
      determined by TUNEL assay. KEY RESULTS: Diazoxide (100 microM) induced
      translocation of PKC-epsilon from the cytosolic to the mitochondrial fraction.
      Specific blockade of PKC-epsilon by either epsilonV1-2 or dominant negative
      mutant PKC-epsilon (PKC-epsilon KR) abolished the anti-apoptotic effect of
      diazoxide. Diazoxide-induced flavoprotein oxidation was inhibited by either
      epsilonV1-2 or PKC-epsilon KR transfection. Treatment with 5-hydroxydecanoate (5
      HD) did not affect translocation and activation of PKC-epsilon induced by
      diazoxide. Transfection with wild type PKC-epsilon mimicked the flavoprotein
      oxidizing effect of diazoxide, and this effect was completely blocked by
      epsilonV1-2 or 5-HD. Diazoxide prevented the increase in mitochondrial Ca(2+),
      mitochondrial depolarization and cytochrome c release induced by hypoxia and all
      these effects of diazoxide were blocked by epsilonV1-2 or 5-HD. CONCLUSIONS AND
      IMPLICATIONS: Diazoxide induced isoform-specific translocation of PKC-epsilon as
      an upstream signaling molecule for the mitoK(ATP) channel, rendering
      cardiomyocytes resistant to hypoxic injury through inhibition of the
      mitochondrial death pathway.

PMID- 17043674
TI  - Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in
      a rat liver cell line (TRL 1215).
AB  - BACKGROUND AND PURPOSE: Although inorganic arsenite (As(III)) is toxic in humans,
      it has recently emerged as an effective chemotherapeutic agent for acute
      promyelocytic leukemia (APL). In humans and most animals, As(III) is
      enzymatically methylated in the liver to weakly toxic dimethylarsinic acid
      (DMAs(V)) that is a major pentavalent methylarsenic metabolite. Recent reports
      have indicated that trivalent methylarsenicals are produced through methylation
      of As(III) and participate in arsenic poisoning. Trivalent methylarsenicals may
      be generated as arsenical-glutathione conjugates, such as dimethylarsinous
      glutathione (DMAs(III)G), during the methylation process. However, less
      information is available on the cytotoxicity of DMAs(III)G. EXPERIMENTAL
      APPROACH: We synthesized and purified DMAs(III)G using high performance TLC
      (HPTLC) methods and measured its cytotoxicity in rat liver cell line (TRL 1215
      cells). KEY RESULTS: DMAs(III)G was highly cytotoxic in TRL 1215 cells with a
      LC(50) of 160 nM. We also found that DMAs(III)G molecule itself was not
      transported efficiently into the cells and was not cytotoxic; however it readily
      became strongly cytotoxic by dissociating into trivalent dimethylarsenicals and
      glutathione (GSH). The addition of GSH in micromolar physiological concentrations
      prevented the breakdown of DMAs(III)G, and the DMAs(III)G-induced cytotoxicity.
      Physiological concentrations of normal human serum (HS), human serum albumin
      (HSA), and human red blood cells (HRBC) also reduced both the cytotoxicity and
      cellular arsenic uptake induced by exposure to DMAs(III)G. CONCLUSIONS AND
      IMPLICATIONS: These findings suggest that the significant cytotoxicity induced by
      DMAs(III)G may not be seen in healthy humans, even if DMAs(III)G is formed in the
      body from As(III).

PMID- 17043676
TI  - Violent behavior associated with hypocholesterolemia due to a novel APOB gene
      mutation.
AB  - A 26-year-old male, the index patient, presented with persecutory delusions and
      suicidal behavior. He had 10 paternal male relatives in two prior generations.
      Five of them died by violent suicide and one, of the five, also committed a
      double homicide. The index patient was found to be hypocholesterolemic due to
      being heterozygous for a novel mutation of apolipoprotein B (apoB-29.4). His
      mother and paternal grandmother were normocholesterolemic, whereas a surviving
      paternal uncle was hypocholesterolemic and heterozygous for the apoB-29.4
      mutation. This indicated that the index patient's father and paternal
      grandfather, both of which died by violent suicide, were obligate heterozygotes
      for the apoB-29.4 mutation and that the index patient inherited the mutation from
      his paternal grandfather. The odds ratio for the association between
      hypocholesterolemia and violent behavior in this family, where cholesterol status
      was known, was 16.9 (95% confidence interval 1.1-239.3). Therefore, our results
      support an inheritable relationship between violent behavior and
      hypocholesterolemia.

PMID- 17043677
TI  - Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of
      risk genes and a potential synaptic basis for schizophrenia.
AB  - Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with
      cognitive deficits in both schizophrenics and the normal ageing population. In
      this study, we have generated a network of protein-protein interactions (PPIs)
      around DISC1. This has been achieved by utilising iterative yeast-two hybrid
      (Y2H) screens, combined with detailed pathway and functional analysis. This so
      called 'DISC1 interactome' contains many novel PPIs and provides a molecular
      framework to explore the function of DISC1. The network implicates DISC1 in
      processes of cytoskeletal stability and organisation, intracellular transport and
      cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent
      with that of an essential synaptic protein, which fits well with the underlying
      molecular pathology observed at the synaptic level and the cognitive deficits
      seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin
      (DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1
      share common PPIs suggesting they may affect common biological processes and that
      the function of schizophrenia risk genes may converge.

PMID- 17043678
TI  - Reduced semen quality in chronic prostatitis patients that induce the release of
      apoptotic protein Omi/HtrA2 from spermatozoa.
AB  - The relationship between chronic prostatitis and fertility has been disputed for
      many years. Several groups have shown infection and autoimmune response against
      prostate antigens could have a deleterious effect on semen quality and fertility.
      This study was conducted to test the hypothesis that Omi/HtrA2-induced apoptosis
      in chronic prostatitis could be a mechanism underlying the observed clinical
      benefit. The Omi/HtrA2 serine protease is a nuclear-encoded mitochondrial
      protein, which can be released from mitochondria into the cytosol after apoptosis
      stimuli, inducing apoptosis in caspase-dependent and independent manners. Forty
      one patients diagnosed as suffering from chronic prostatitis were included.
      Healthy normal individuals were included as controls. Human spermatozoa in the
      semen were purified by Percoll-gradient technique to separate the seminal plasma
      and other round cells. Measurements for sperm concentration, motility,
      morphology, proinflammatory cytokines, Omi/HtrA2 mRNA and protein levels in
      spermatozoa of chronic protatitis patients, were performed accordingly.
      Significantly increased levels of proinflammatory cytokines were detected in
      seminal plasma from these prostatitis patients. Omi/HtrA2 mRNA and protein levels
      were significantly higher in prostatitis men than in normal men. This study shows
      that chronic prostatitis patients present important alterations in their semen
      quality parameters, Omi/HtrA2 mRNA and protein levels of spermatozoa. We
      speculate that the inflammatory process involved may affect male fertility by
      release of proapoptotic protein Omi/HtrA2.

PMID- 17043680
TI  - The treatment of spasticity with Delta9-tetrahydrocannabinol in persons with
      spinal cord injury.
AB  - STUDY DESIGN: Open label study to determine drug dose for a randomized double
      blind placebo-controlled parallel study. OBJECTIVES: To assess the efficacy and
      side effects of oral Delta(9)-tetrahydrocannabinol (THC) and rectal THC
      hemisuccinate (THC-HS) in SCI patients. SETTING: REHAB Basel, Switzerland.
      METHOD: Twenty-five patients with SCI were included in this three-phase study
      with individual dose adjustment, each consisting of 6 weeks. Twenty-two
      participants received oral THC open label starting with a single dose of 10 mg
      (Phase 1, completed by 15 patients). Eight subjects received rectal THC-HS (Phase
      2, completed by seven patients). In Phase 3, six patients were treated with oral
      THC and seven with placebo. Major outcome parameters were the spasticity sum
      score (SSS) using the Modified Ashworth Scale (MAS) and self-ratings of
      spasticity. RESULTS: Mean daily doses were 31 mg with THC and 43 mg with THC-HS.
      Mean SSS for THC decreased significantly from 16.72 (+/-7.60) at baseline to 8.92
      (+/-7.14) on day 43. Similar improvement was seen with THC-HS. We observed a
      significant improvement of SSS with active drug (P=0.001) in the seven subjects
      who received oral THC in Phase 1 and placebo in Phase 3. Major reasons for drop
      out were increase of pain and psychological side effects. CONCLUSION: THC is an
      effective and safe drug in the treatment of spasticity. At least 15-20 mg per day
      were needed to achieve a therapeutic effect.

PMID- 17043681
TI  - Spinal-injured neuropathic bladder antisepsis (SINBA) trial.
AB  - OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets
      prevent urinary tract infections (UTI) in people with neuropathic bladder
      following spinal cord injury (SCI). STUDY DESIGN: Double-blind factorial-design
      randomized controlled trial (RCT) with 2 year recruitment period from November
      2000 and 6 month follow-up. SETTING: In total, 543 eligible predominantly
      community dwelling patients were invited to participate in the study, of whom 305
      (56%) agreed. METHODS: Eligible participants were people with SCI with neurogenic
      bladder and stable bladder management. All regimens were indistinguishable in
      appearance and taste. The dose of MH used was 1 g twice-daily. The dose of
      cranberry used was 800 mg twice-daily. The main outcome measure was the time to
      occurrence of a symptomatic UTI. RESULTS: Multivariate analysis revealed that
      patients randomized to MH did not have a significantly longer UTI-free period
      compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to
      cranberry likewise did not have significantly longer UTI-free period compared to
      placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70). CONCLUSION: There is no benefit in
      the prevention of UTI from the addition of MH or cranberry tablets to the usual
      regimen of patients with neuropathic bladder following SCI.

PMID- 17043683
TI  - Is thymidylate synthase a reliable predictor for response and survival during
      hepatic arterial infusion for hepatic metastases from colorectal cancer?

PMID- 17043684
TI  - A third-generation bisphosphonate, minodronic acid (YM529), successfully
      prevented the growth of bladder cancer in vitro and in vivo.
AB  - Minodronic acid (YM529) is a third-generation bisphosphonate (BP) that has been
      shown to directly and indirectly prevent proliferation, induce apoptosis, and
      inhibit metastasis of various types of cancer cells. In this study, we have
      investigated the therapeutic efficacy of YM529 against bladder cancer, both in
      vitro and in vivo. YM529 inhibited geranylgeranylation as well as farnesylation
      and reduced the growth of all seven bladder cancer cell lines in a dose- and time
      dependent manner in vitro. YM529 demonstrated a good synergistic or additive
      antiproliferative effect when administered in combination with cisplatin or
      paclitaxel. Immunohistochemical study revealed YM529 inhibited the prenylation of
      Rap1A in vivo. YM529 administered systemically did not markedly inhibit the
      growth of visceral metastases but it showed a significant anticancer effect on
      bone metastases monitored by an in vivo imaging system. Moreover, intravesical
      YM529 demonstrated significant growth inhibition in a bladder cancer orthotopic
      model. No adverse effects were associated with the systemic as well as the
      intravesical treatment regimens. In conclusion, our study suggests that YM529 may
      be a potent anticancer agent for bladder cancer. The efficacy and safety of this
      BP as an agent for combination chemotherapies against bladder cancer should be
      verified by early-phase clinical trials.

PMID- 17043685
TI  - Mastectomy rates are decreasing in the era of service screening: a population
      based study in Italy (1997-2001).
AB  - We enrolled all 2162 in situ and 21 148 invasive cases of breast cancer in 17
      areas of Italy, diagnosed in 1997-2001. Rates of early cancer increased by 13.7%
      in the screening age group (50-69 years), and breast conserving surgery by 24.6%.
      Advanced cancer rates decreased by 19.4%, and mastectomy rates by 24.2%. Service
      screening did not increase mastectomy rates in the study population.

PMID- 17043686
TI  - Lung cancer risk among German male uranium miners: a cohort study, 1946-1998.
AB  - From 1946 to 1990 extensive uranium mining was conducted in the southern parts of
      the former German Democratic Republic. The overall workforce included several
      100,000 individuals. A cohort of 59,001 former male employees of the Wismut
      Company was established, forming a large retrospective uranium miners' cohort for
      the time period 1946-1998. Mean duration of follow-up was 30.5 years with a total
      of 1 801,630 person-years. Loss to follow-up was low at 5.3%. Of the workers,
      16,598 (28.1%) died during the study period. Based on 2388 lung cancer deaths,
      the radon-related lung cancer risk is evaluated. The excess relative risk (ERR)
      per working level month (WLM) was estimated as 0.21% (95% CI: 0.18-0.24). It was
      dependent on time since exposure and on attained age. The highest ERR/WLM was
      observed 15-24 years after exposure and in the youngest age group (<55 years of
      age). While a strong inverse exposure-rate effect was detected for high
      exposures, no significant association was detected at exposures below 100 WLM.
      Excess relative risk /WLM was not modified by duration of exposure. The results
      would indicate the need to re-estimate the effects of risk modifying factors in
      current risk models as duration of exposure did not modify the ERR/WLM and there
      was only a modest decline of ERR/WLM with increasing time since exposure.

PMID- 17043688
TI  - "I Can't Believe We Don't Know That!".

PMID- 17043689
TI  - Low-load eversion force sense, self-reported ankle instability, and frequency of
      giving way.
AB  - CONTEXT: Functional ankle instability has been attributed to proprioceptive loss.
      However, in previous studies of proprioception,authors have not investigated the
      ability to sense force at the ankle. Additionally, previous investigators have
      viewed functional ankle instability as either a present or absent
      condition,rather than a continuum. OBJECTIVE: To determine the relationship of
      ankle giving-way frequency and perceived ankle instability to ankle eversion
      force sense. DESIGN: Cohort design. SETTING: Sports medicine research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty individuals (5 men,15 women) with a
      history of unilateral ankle instability. INTERVENTION(S): We tested subjects with
      2 loads: 10% and 30% of maximal voluntary isometric contraction. MAIN OUTCOME
      MEASURE(S): We measured eversion force sense by calculating absolute, constant,
      and variable errors from a 3-trial force-matching procedure. Furthermore,
      subjects reported their frequency of giving way in units of times per day,week,
      or month, and these data were extrapolated to estimate annual giving-way
      frequency. Finally, subjects answers to 6 questions about ankle stability during
      typical daily or sports activities were summed to create a perceived ankle
      instability index. RESULTS: Significant relationships were found for only the 10%
      maximal voluntary isometric contraction. For absolute error,a positive
      relationship existed between the number of self reported episodes of giving way
      and eversion force sense for both ipsilateral (r .58) and contralateral (r .49)
      testing of the injured ankle. Constant error was correlated with giving way(r = 
      .56) for ipsilateral testing of the injured ankle. The ankle instability index
      was also positively correlated with eversion force sense absolute error (r .51)
      for ipsilateral testing only. CONCLUSIONS: Our results suggest that subjects with
      ankle instability had difficulty replicating eversion forces. Specifically,larger
      errors were related to both self-reported giving-way episodes and perceived ankle
      instability.

PMID- 17043687
TI  - Insulin receptor substrates mediate distinct biological responses to insulin-like
      growth factor receptor activation in breast cancer cells.
AB  - Activation of the type I insulin-like growth factor receptor (IGF-IR) regulates
      several aspects of the malignant phenotype, including cancer cell proliferation
      and metastasis. Phosphorylation of adaptor proteins downstream of IGF-IR may
      couple IGF action to specific cancer phenotypes. In this study, we sought to
      determine if insulin receptor substrate-1 and -2 (IRS-1 and -2) mediate distinct
      biological effects in breast cancer cells. Insulin receptor substrate-1 and IRS-2
      were expressed in T47D-YA breast cancer cells, which lack IRS-1 and -2
      expression, yet retain functional IGF-IR. In the absence of IRS-1 and -2
      expression, IGF-IR activation was unable to stimulate proliferation or motility
      in T47D-YA cells. Expression of IRS-1 resulted in IGF-I-stimulated proliferation,
      but did not affect motility. In contrast, expression of IRS-2 enhanced IGF-I
      stimulated motility, but did not stimulate proliferation. The alphaIR-3, an
      inhibitor of the IGF-IR, was unable to affect these IGF-stimulated phenotypes
      unless IRS-1 or -2 was expressed. Thus, IGF-IR alone is unable to regulate
      important breast cancer cell phenotypes. In these cells, IRS proteins are
      required for and mediate distinct aspects of IGF-IR-stimulated behaviour. As
      multiple agents targeting the IGF-IR are currently in early clinical trials, IRS
      expression should be considered as a potential biomarker for IGF-IR
      responsiveness.

PMID- 17043690
TI  - Prophylactic ankle braces and knee varus-valgus and internal-external rotation
      torque.
AB  - CONTEXT: Although prophylactic ankle bracing has been shown to be effective in
      reducing the incidence of ankle sprains,how these ankle braces might affect the
      other joints of the lower extremity is not clearly understood. OBJECTIVE: To
      determine the effects of a prophylactic ankle brace on knee joint varus-valgus
      and internal-external rotation torque during a drop landing onto a slanted
      surface. DESIGN: A repeated-measures design. SETTING: Biomechanics research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four physically active college
      students. INTERVENTION(S): Participants were tested in a brace and no brace
      condition. MAIN OUTCOME MEASURE(S): We measured 3 dependent variables:(1) peak
      ankle inversion-eversion torque, (2) peak knee varus-valgus torque, and (3) peak
      knee internal-external rotation torque. A force plate was used to collect ground
      reaction force data, and 6 motion analysis cameras collected kinematic data
      during the unilateral drop landing. An adjustable bar was hung from the ceiling,
      and a slant board was positioned over the center of the force plate, so that the
      ankle of the participant's dominant leg would invert upon landing. Peak torque
      was measure din both the brace and no-brace conditions. The average of the peak
      values in 3 trials for both conditions was used for the statistical analysis.
      RESULTS: Ankle eversion torque was significantly greater in the brace condition
      (F1,23 19.75, P < .01). Knee external rotation torque was significantly greater
      in the brace condition(F1,23 4.33, P <.05). Valgus knee torque was smaller in the
      brace condition, but the difference was not statistically significant(F1,23 3.45,
      P .08). CONCLUSIONS: This study provides an important first step in understanding
      the effects of prophylactic ankle bracing on other joints of the lower extremity.
      We found that prophylactic ankle bracing did have an effect on knee torque when
      the subject was landing on a slanted surface. Specifically, knee external
      rotation torque increased when the ankle was braced.

PMID- 17043691
TI  - Dynamic postural stability in subjects with braced, functionally unstable ankles.
AB  - CONTEXT: Research concerning prophylactic ankle stabilizers (PASs) has focused on
      healthy subjects, and the results cannot be generalized to the functional ankle
      instability (FAI) population, a population that has an increased risk of reinjury
      and is likely to wear PASs. OBJECTIVE: To determine whether PASs improve dynamic
      postural stability in FAI subjects as compared with a control (no-brace)
      condition. DESIGN: A crossover design was used to determine the effects of PASs
      on dynamic postural stability and vertical ground reaction forces. SETTING:
      Biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-eight subjects
      with unilateral FAI, 13 men (age = 21.5 +/- 1.2 years, height = 181.5 +/- 10.5
      cm, mass = 77.6 +/- 17.2 kg) and 15 women (age = 20.5 +/- 1.1 years, height =
      169.4 +/- 8.2 cm, mass = 67.9 +/- 8.8 kg). INTERVENTION(S): A jump protocol
      required subjects to perform a 2-legged jump to a height equivalent to 50% of
      their maximum vertical leap and land on a single leg. MAIN OUTCOME MEASURE(S):
      The dynamic postural stability index, the directional components (medial-lateral,
      anterior-posterior, and vertical), and vertical ground reaction force after a
      jump landing. RESULTS: Compared with the control condition, only the vertical
      component score was reduced (improved) with the application of a soft or
      semirigid PAS (P < .01). CONCLUSIONS: Soft and semirigid PASs did not improve
      dynamic postural stability as measured by the Dynamic Postural Stability Index.
      However, PASs may help with the attenuation of vertical forces.

PMID- 17043692
TI  - The independent and interactive effects of navicular drop and quadriceps angle on
      neuromuscular responses to a weight-bearing perturbation.
AB  - CONTEXT: Little is known about the effects of static alignment on neuromuscular
      control of the knee during dynamic motion. OBJECTIVE: To evaluate the isolated
      and combined effects of quadriceps angle (QA) and navicular drop (ND) on
      neuromuscular responses to a weight-bearing perturbation. DESIGN: Mixed-model,
      repeated-measures design. SETTING: Sports medicine and athletic training research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Seventy-nine National Collegiate
      Athletic Association Division I collegiate female athletes, classified with below
      average ND and QA (LND-LQA); below-average ND and above-average QA (LND-HQA);
      above-average ND and below-average QA (HND-LQA); or above-average ND and QA (HND
      HQA). INTERVENTION(S): A lower extremity perturbation device produced a forward
      and either internal or external rotation of the trunk and femur on the weight
      bearing tibia to evoke a reflex response. MAIN OUTCOME MEASURE(S): Neuromuscular
      responses were examined in the quadriceps, hamstrings, and gastrocnemius muscles:
      preperturbation amplitude 50 milliseconds before the perturbation, reflex time,
      and postperturbation amplitude 150 milliseconds immediately postperturbation.
      RESULTS: Navicular drop had the greatest effect on preperturbation amplitude of
      the lateral hamstrings and postperturbation amplitude of all muscles, with
      greater activation amplitude noted in subjects in the HND classifications.
      Quadriceps angle primarily affected reflex time of the quadriceps; in subjects
      with LQA, reflex time was faster for internal rotation than external rotation
      perturbations. The interaction between ND and QA had the greatest effect on
      reflex time of the lateral hamstrings. For internal rotation perturbations,
      subjects in the LND classifications had faster reflex times in the lateral
      hamstrings if they had HQA values rather than LQA values. With external rotation
      perturbations, HND-LQA subjects had slower reflex times than those in all other
      alignment classifications. CONCLUSIONS: Navicular drop and QA have both
      independent and interactive effects on neuromuscular responses to a weight
      bearing, rotational perturbation. These interactive effects highlight the
      importance of considering the entire lower extremity posture rather than a single
      alignment characteristic, given the potential for one alignment factor to
      compensate for or interact with another.

PMID- 17043693
TI  - Quadriceps inhibition after repetitive lumbar extension exercise in persons with
      a history of low back pain.
AB  - CONTEXT: A neuromuscular relationship exists between the lumbar extensor and
      quadriceps muscles during fatiguing exercise. However, this relationship may be
      different for persons with low back pain (LBP). OBJECTIVE: To compare quadriceps
      inhibition after isometric, fatiguing lumbar extension exercise between persons
      with a history of LBP and control subjects. DESIGN: A 2 x 3 factorial, repeated
      measures, time-series design with independent variables of group (persons with a
      history of LBP, controls) and time (baseline, postexercise set 1, postexercise
      set 2). SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twenty-five subjects with a history of LBP were matched by sex, height, and mass
      to 25 healthy control subjects. INTERVENTION(S): Electromyography median
      frequency indexed lumbar paraspinal muscular fatigue while subjects performed 2
      sets of isometric lumbar extension exercise. Subjects exercised until a 15%
      downward shift in median frequency for the first set and a 25% shift for the
      second set were demonstrated. MAIN OUTCOME MEASURE(S): Knee extension force was
      measured while subjects performed an isometric maximal quadriceps contraction.
      During this maximal effort, a percutaneous electric stimulus was applied to the
      quadriceps, causing a transient, supramaximal increase in force output. We used
      the ratio between the 2 forces to estimate quadriceps inhibition. Quadriceps
      electromyographic activity was recorded during the maximal contractions to
      compare median frequencies over time. RESULTS: Both groups exhibited
      significantly increased quadriceps inhibition after the first (12.6% +/- 10.0%, P
      < .001) and second (15.2% +/- 9.7%, P < .001) exercise sets compared with
      baseline (9.6% +/- 9.3%). However, quadriceps inhibition was not different
      between groups. CONCLUSIONS: Persons with a history of LBP do not appear to be
      any more or less vulnerable to quadriceps inhibition after fatiguing lumbar
      extension exercise.

PMID- 17043694
TI  - Acute muscle stretching and shoulder position sense.
AB  - CONTEXT: Stretching is common among athletes as a potential method for injury
      prevention. Stretching-induced changes in the muscle spindle properties are a
      suggested mechanism, which may imply reduced proprioception after stretching;
      however, little is known of this association. OBJECTIVE: To evaluate whether
      acute stretching of the shoulder muscles affects position sense. DESIGN: A
      crossover design with subjects randomized to 3 groups. SETTING: A university
      human research laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine male (age = 24 +/
      3 years) and 9 female (age = 21 +/- 2 years) healthy volunteers.
      INTERVENTION(S): Stretching of shoulder (1) agonists or (2) antagonists or (3)
      nonstretching control. MAIN OUTCOME MEASURE(S): We determined position sense
      acuity of the right shoulder before and after the interventions by having
      subjects attempt to reproduce arm positions of 15 degrees and 30 degrees
      (shoulder adduction) while starting at 45 degrees to the sagittal plane. The
      outcome variables were response variability (variable error) and overall accuracy
      (absolute error). RESULTS: The relative change in variable error (ie, variable
      error after/variable error before) was not significantly different between the
      interventions ( P = .38). Similarly, no change in absolute error was found ( P =
      .76). Furthermore, no differences were noted regarding test sequence or the
      interaction of intervention x sequence for either variable error ( P = .73 and
      .53, respectively) or absolute error ( P = .71 and .67, respectively).
      CONCLUSIONS: We found no effect on shoulder position sense after an acute bout of
      stretching of either agonist or antagonist shoulder muscles.

PMID- 17043695
TI  - A functional fatiguing protocol and deceleration time of the shoulder from an
      internal rotation perturbation.
AB  - CONTEXT: Muscular fatigue impedes sensorimotor function and may increase the risk
      of shoulder injury during activity. The effects of fatigue on the sensorimotor
      system of the shoulder have been studied with various results. Deceleration times
      have been used to study neuromuscular control of the shoulder; however, no
      studies involving the effects of fatigue on deceleration times have been
      reported. OBJECTIVE: To compare shoulder deceleration times after a shoulder
      internal rotation perturbation before and after a repetitive throwing exercise
      protocol. DESIGN: A 2 x 2 repeated-measures design. SETTING: Exercise and sport
      injury laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy, recreationally
      active men (age = 24.76 +/- 4.03 years, height = 178.41 +/- 8.36 cm, mass = 80.16
      +/- 15.20 kg) volunteered to participate in the study. To ensure familiarity with
      the overhead motion, all subjects chosen had previously participated in an
      overhead throwing sport. INTERVENTION(S): The independent variables were time
      (preintervention and postintervention) and session (experimental and control).
      The intervention consisted of continuous overhead throwing. The subjects were
      considered fatigued when a 10% decrease in velocity was noted on 3 consecutive
      pitches. MAIN OUTCOME MEASURE(S): Time necessary to decelerate from an internal
      rotation perturbation. RESULTS: Deceleration time was significantly increased by
      the fatiguing intervention ( P = .001). CONCLUSIONS: The decreased ability to
      decelerate may be an adaptive response by the subjects to dissipate a lower
      percentage of force per second.

PMID- 17043696
TI  - Flexible foil exercise and shoulder internal and external rotation strength.
AB  - CONTEXT: The efficacy of exercise using a flexible foil to increase strength in
      the shoulder rotator muscles is unknown. OBJECTIVE: To compare the effects of
      exercises using a flexible foil (Bodyblade) with exercises using elastic bands on
      shoulder internal and external rotator muscle strength. DESIGN: We used a
      randomized, controlled pretest-posttest design. SETTING: Laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Forty young adults with no previous shoulder injury.
      INTERVENTION(S): Experimental subjects participated in an 8-week program of
      internal and external rotation exercises consisting of 3 sessions per week. MAIN
      OUTCOME MEASURE(S): Strength was tested by internal and external rotation
      isometric and isokinetic strength tests at 60 degrees .s (-1) and 120 degrees .s
      (-1). RESULTS: The group exercising with elastic bands had a greater pretest
      posttest increase in maximal internal rotation isometric torque at 10 degrees of
      internal rotation and greater maximal external rotation isometric torque at 65
      degrees of external rotation than the control group. The group using a flexible
      foil did not show an increase in strength significantly different from either the
      control or elastic band groups. We found no other statistically significant
      differences. CONCLUSIONS: Our results do not support the use of a flexible foil
      for strength gains in shoulder internal and external rotation in the asymptomatic
      young adult population.

PMID- 17043697
TI  - Improving strength and postural control in young skiers: whole-body vibration
      versus equivalent resistance training.
AB  - CONTEXT: Several groups have undertaken studies to evaluate the physiologic
      effects of whole-body vibration (WBV). However, the value of WBV in a training
      program remains unknown. OBJECTIVE: To investigate whether a WBV program results
      in a better strength and postural control performance than an equivalent exercise
      program performed without vibration. DESIGN: Randomized, controlled trial.
      SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-three Belgian
      competitive skiers (ages = 9-15 years). INTERVENTION(S): Subjects were assigned
      to either the WBV group or the equivalent resistance (ER) group for 6 weeks of
      training at 3 times per week. MAIN OUTCOME MEASURE(S): Isokinetic plantar and
      dorsiflexion peak torque, isokinetic knee flexion and extension peak torque,
      explosive strength (high box test), and postural control were assessed before and
      after the training period. RESULTS: Both training programs significantly improved
      isokinetic ankle and knee muscle strength and explosive strength. Moreover, the
      increases in explosive strength and in plantar-flexor strength at low speed were
      significantly higher in the WBV group than in the ER group after 6 weeks.
      However, neither WBV training nor ER training seemed to have an effect on
      postural control. CONCLUSIONS: A strength training program that includes WBV
      appears to have additive effects in young skiers compared with an equivalent
      program that does not include WBV. Therefore, our findings support the hypothesis
      that WBV training may be a beneficial supplementary training technique in
      strength programs for young athletes.

PMID- 17043698
TI  - Fatigue, vertical leg stiffness, and stiffness control strategies in males and
      females.
AB  - CONTEXT: Fatigue appears to influence musculoskeletal injury rates during
      athletic activities, but whether males and females respond differently to fatigue
      is unknown. OBJECTIVE: To determine the influence of fatigue on vertical leg
      stiffness (K (VERT)) and muscle activation and joint movement strategies and
      whether healthy males and females respond similarly to fatigue. DESIGN: Repeated
      measures design with all data collected during a single laboratory session.
      SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Physically active males (n =
      11) and females (n = 10). INTERVENTION(S): Subjects performed hopping protocols
      at 2 frequencies before and after fatigue, which was induced by repeated
      squatting at submaximal loads. MAIN OUTCOME MEASURE(S): We measured K (VERT) with
      a forceplate and peak muscle activity of the quadriceps, hamstrings,
      gastrocnemius, soleus, and anterior tibialis muscles with surface
      electromyography. Sagittal-plane kinematics at the knee and ankle were recorded
      with an electrogoniometer. RESULTS: After fatigue, K (VERT) was unchanged for all
      subjects. However, both males and females demonstrated reduced peak hamstrings (
      P = .002) and anterior tibialis ( P = .001) activation, coupled with increased
      gastrocnemius ( P = .005) and soleus ( P = .001) peak activity, as well as
      increased quadriceps-hamstrings ( P = .005) and gastrocnemius/soleus-anterior
      tibialis coactivation ratios ( P = .03) after fatigue. Overall, females
      demonstrated greater quadriceps-hamstrings coactivation ratios than males,
      regardless of the fatigue condition ( P = .026). Only females showed increased
      knee flexion at initial contact after fatigue during hopping ( P = .03).
      CONCLUSIONS: Although K (VERT) was unaffected, the peak muscle activation and
      joint movement strategies used to modulate K (VERT) were affected after fatigue.
      Once fatigued, both males and females used an ankle-dominant strategy, with
      greater reliance on the ankle musculature and less on the knee musculature. Also,
      once fatigued, all subjects used an antagonist inhibition strategy by minimizing
      antagonist coactivation. Overall, females used a more quadriceps-dominant
      strategy than males, showing greater quadriceps activity and a larger quadriceps
      hamstrings coactivation ratio. Changes in muscle activation and coactivation
      ratios because of fatigue and sex are suggested to alter knee joint stability and
      increase anterior cruciate ligament injury risk.

PMID- 17043699
TI  - Recovery of postural control after cerebral concussion: new insights using
      approximate entropy.
AB  - CONTEXT: The return-to-play decision after sport-related cerebral concussion
      depends in part on knowing when an athlete has fully recovered postural control
      after injury. OBJECTIVE: To describe the postconcussion recovery of postural
      control using approximate entropy (ApEn), a regularity statistic from nonlinear
      dynamics. DESIGN: Retrospective case series analysis. SETTING: Sports medicine
      research laboratory. PATIENTS OR OTHER PARTICIPANTS: Collegiate athletes from
      whom center-of-pressure and symptom data were collected at preseason, less than
      48 hours after injury, and 48 to 96 hours after injury. MAIN OUTCOME MEASURE(S):
      Approximate entropy values reflecting the amount of randomness contained in
      center-of-pressure oscillations were calculated for anterior-posterior (AP) and
      medial-lateral (ML) time series. Equilibrium scores reflecting the amplitude of
      center-of-pressure AP oscillations were used to indicate postural stability. The
      number and severity of symptoms were described. RESULTS: Compared with the
      healthy preseason state, ApEn values for the AP and ML time series generally
      declined immediately after injury in both steady and unsteady injured athletes.
      At 48 to 96 hours after injury, ApEn values for the ML time series remained
      significantly depressed (mean difference compared with preseason = -0.268,
      standard error = 0.072), even among athletes whose initial postural instability
      had resolved. We found few significant relationships between changes in ApEn
      values and changes in symptoms before and after injury. CONCLUSIONS: The effects
      of cerebral concussion on postural control appear to persist for longer than 3 to
      4 days, even among athletes with no signs of unsteadiness. Our results may
      reflect changes in neurophysiologic or mechanical constraints on postural
      control. Approximate entropy provides a theoretically distinct, valuable
      measurement alternative that may prove useful for reducing uncertainty in the
      return-to-play decision.

PMID- 17043700
TI  - Surface electromyographic amplitude-to-work ratios during isokinetic and isotonic
      muscle actions.
AB  - CONTEXT: Isokinetic and isotonic resistance training exercises are commonly used
      to increase strength during musculoskeletal rehabilitation programs. Our study
      was designed to examine the efficacy of isokinetic and isotonic muscle actions
      using surface electromyographic (EMG) amplitude-to-work ratios (EMG/WK) and to
      extend previous findings to include a range of isokinetic velocities and isotonic
      loads. OBJECTIVE: To examine work (WK), surface EMG amplitude, and EMG/WK during
      concentric-only maximal isokinetic muscle actions at 60, 120, 180, 240, and 300
      degrees /s and isotonic muscle actions at 10%, 20%, 30%, 40%, and 50% of the
      maximal voluntary isometric contraction (MVIC) torque during leg extension
      exercises. DESIGN: A randomized, counterbalanced, cross-sectional, repeated
      measures design. SETTING: A university-based human muscle physiology research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten women (mean age = 22.0 +/- 2.6
      years) and 10 men (mean age = 20.8 +/- 1.7 years) who were apparently healthy and
      recreationally active. INTERVENTION(S): Using the dominant leg, each participant
      performed 5 maximal voluntary concentric isokinetic leg extension exercises at
      randomly ordered angular velocities of 60, 120, 180, 240, and 300 degrees /s and
      5 concentric isotonic leg extension exercises at randomly ordered loads of 10%,
      20%, 30%, 40%, and 50% of the isometric MVIC. MAIN OUTCOME MEASURE(S): Work was
      recorded by a Biodex System 3 dynamometer, and surface EMG was recorded from the
      superficial quadriceps femoris muscles (vastus lateralis, rectus femoris, and
      vastus medialis) during the testing and was normalized to the MVIC. The EMG/WK
      ratios were calculated as the quotient of EMG amplitude (muVrms) and WK (J)
      during the concentric phase of each exercise. RESULTS: Isotonic EMG/WK remained
      unchanged ( P > .05) from 10% to 50% MVIC, but isokinetic EMG/WK increased ( P <
      .05) from 60 to 300 degrees /s. Isotonic EMG/WK was greater ( P < .05) than
      isokinetic EMG/WK for 50% MVIC versus 60 degrees /s, 40% MVIC versus 120 degrees
      /s, and 30% MVIC versus 180 degrees /s; however, no differences were noted ( P >
      .05) between 20% MVIC versus 240 degrees /s or 10% MVIC versus 300 degrees /s. An
      18% decrease in active range of motion was seen for the isotonic muscle actions,
      from 10% to 50% MVIC, and a 3% increase in range of motion for the isokinetic
      muscle actions from 60 to 300 degrees /s was also observed. Furthermore, the peak
      angular velocities for the isotonic muscle actions ranged from 272.9 to 483.0
      degrees /s for 50% and 10% MVIC, respectively. CONCLUSIONS: When considering
      EMG/WK, peak angular velocity, and range of motion together, our data indicate
      that maximal isokinetic muscle actions at 240 degrees /s or controlled-velocity
      isotonic muscle actions at 10%, 20%, or 30% MVIC may maximize the amount of
      muscle activation per unit of WK done during the early stages of musculoskeletal
      rehabilitation. These results may be useful to allied health professionals who
      incorporate open-chain resistance training exercises during the early phases of
      rehabilitation and researchers who use isotonic or isokinetic modes of resistance
      exercise to examine muscle function.

PMID- 17043701
TI  - Cortisol concentrations in human skeletal muscle tissue after phonophoresis with
      10% hydrocortisone gel.
AB  - CONTEXT: The delivery of hydrocortisone through phonophoresis is a widely
      prescribed technique for the treatment of various musculoskeletal inflammatory
      conditions. However, limited scientific evidence exists to support the efficacy
      of phonophoresis in delivering hydrocortisone to skeletal muscle tissue in
      humans. OBJECTIVE: To determine hydrocortisone (cortisol) concentrations in human
      skeletal muscle tissue after a phonophoresis treatment using 10% hydrocortisone
      gel. DESIGN: Randomized design in which 12 subjects were randomly assigned to
      either an ultrasound (sham) treatment or a 10% hydrocortisone phonophoresis
      treatment. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve healthy
      subjects (8 women, 4 men: age = 22.3 +/- 2.64 years, height = 168.28 +/- 8.19 cm,
      mass = 69.58 +/- 9.05 kg) with no history of musculoskeletal disease, preexisting
      inflammatory conditions, or recent orthopaedic injuries. INTERVENTION(S):
      Ultrasound at 1.0 MHz, 1.0 W/cm (2), at a continuous setting for 7 minutes was
      applied to a standardized area of the vastus lateralis muscle in both groups. The
      contralateral limb served as the control (no treatment) for both the sham and the
      phonophoresis groups. MAIN OUTCOME MEASURE(S): Vastus lateralis muscle biopsies
      were taken from both legs immediately after treatment, and cortisol
      concentrations were analyzed using an enzyme-linked immunosorbent assay. RESULTS:
      We observed no significant difference in muscle cortisol concentration between
      the contralateral control limb and the treatment limb in either the sham or the
      phonophoresis group ( P > .05). No significant difference was noted when the
      treatment limbs in the sham and phonophoresis groups were compared ( P > .05).
      CONCLUSIONS: Our data suggest that a 10% hydrocortisone-based phonophoresis
      treatment did not increase cortisol concentrations in human skeletal muscle
      tissue.

PMID- 17043702
TI  - Injuries sustained by rugby players presenting to United States emergency
      departments, 1978 through 2004.
AB  - CONTEXT: Although the United States has nearly 60 000 rugby players, to date no
      nationally representative rugby injury studies have been conducted. OBJECTIVE: To
      describe rugby players with injuries presenting to a representative sample of US
      emergency departments from 1978 through 2004. DESIGN: Retrospective study.
      SETTING: US Consumer Products Safety Commission's National Electronic Injury
      Surveillance System. PATIENTS OR OTHER PARTICIPANTS: Rugby players presenting to
      emergency departments in participating hospitals from October 1, 1978, through
      December 31, 2004. MAIN OUTCOME MEASURE(S): We reviewed all rugby players with
      injuries captured by the National Electronic Injury Surveillance System and
      categorized them by sex, age, injury site, and injury diagnosis. RESULTS: An
      estimated 236 539 rugby players presented to US emergency departments from 1978
      through 2004. Injured athletes tended to be male (87.2%) and older than 18 years
      of age (86.0%). The face (20.5%), shoulder (14.1%), head (11.5%), and ankle
      (9.1%) were the most frequently injured sites. Strain/sprain (24.3%), laceration
      (22.1%), fracture (18.7%), and contusion/abrasion (16.6%) were the most common
      diagnoses. Males presented with more face injuries (injury proportion ratio [IPR]
      = 2.05, 95% confidence interval [CI] = 1.54-2.72, P < .001) and more lacerations
      (IPR = 4.23, 95% CI = 2.87-6.22, P < .001) and dislocations (IPR = 2.17, 95% CI
      1.51-3.13, P < .001). Females presented with more knee injuries (IPR = 1.67, 95%
      CI = 1.36-2.06, P < .001) and more contusions/abrasions (IPR = 1.48, 95% CI =
      1.14-1.92, P < .001) and strains/sprains (IPR = 1.39, 95% = CI 1.16-1.67, P <
      .001). Those 18 years of age or younger presented with more concussions (IPR =
      1.62, 95% CI = 1.06-2.50, P < .001), while those over 18 presented with more
      lacerations (IPR = 1.83, 95% CI = 1.30-2.57, P < .001). In males, fractures were
      more common among those 18 years of age or younger (IPR = 1.47, 95% CI = 1.24
      1.75, P < .001). CONCLUSIONS: Rugby injury patterns in the United States differed
      by age and sex. Understanding such patterns should assist certified athletic
      trainers in developing targeted preventive interventions.

PMID- 17043703
TI  - Exertional heat illness and environmental conditions during a single football
      season in the southeast.
AB  - CONTEXT: Recommendations for heat illness prevention provided by sports medicine
      associations do not always account for sex differences, specific age populations,
      regional environmental conditions, equipment worn during activity, or the
      athlete's size or preexisting level of fitness. OBJECTIVE: To evaluate the rate
      of exertional heat illness (EHI) among collegiate football athletes and to
      monitor environmental conditions during American football practice for a 3-month
      period. DESIGN: Epidemiologic study in which we reviewed the occurrence rates of
      EHI and wet bulb globe temperature readings during a 3-month period of American
      collegiate football practice sessions. SETTING: Five universities in the
      southeastern region of the United States. PATIENTS OR OTHER PARTICIPANTS:
      Collegiate football players at the 5 universities. MAIN OUTCOME MEASURE(S): Wet
      bulb globe temperatures were recorded from August through October 2003, at the
      beginning, middle, and end of each practice session. The EHIs were identified and
      recorded, and athlete-exposures (AEs) were calculated. RESULTS: A total of 139
      EHIs and 33 196 AEs were reported (EHI rate = 4.19/1000 AEs). The highest
      incidence of EHIs was in August (88%, EHI rate = 8.95/1000 AEs) and consisted of
      70% heat cramps (6.13/1000 AEs), 23% heat exhaustion (2.06/ 1000 AEs), and 7%
      heat syncope (0.58/1000 AEs). No cases of heat stroke or hyponatremia were
      identified. The highest risk of EHI occurred during the first 3 weeks of the
      study; mean wet bulb globe temperature declined significantly as the study
      continued ( P < .001). Temperatures in the final 5 weeks of the study were
      significantly cooler than in the first 5 weeks ( P < .05). CONCLUSIONS: Heat
      cramps were the most common EHI and occurred most often during the first 3 weeks
      of practice. Athletic trainers should take all necessary preventive measures to
      reduce the risk of EHI.

PMID- 17043704
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: prevalence and
      risk factors.

PMID- 17043705
TI  - Central cord syndrome in a high school wrestler: a case report.
AB  - OBJECTIVE: To alert athletic trainers to the importance of recognizing the signs
      and symptoms of central cord syndrome. BACKGROUND: A 15-year-old high school
      wrestler was found lying supine on the mat after sustaining a hyperextension
      injury to his neck while drilling during practice, complaining of numbness,
      tingling, and a burning sensation in all 4 extremities. Touching the extremities
      elicited an extreme burning sensation. After in-line stabilization of the
      cervical spine was performed, palpation of the spinous processes elicited
      tenderness and an increase in pain. Six weeks before the injury, the athlete had
      experienced forced lateral flexion of the cervical spine during a match,
      resulting in an episode of bilateral numbness and burning in his arms. On
      evaluation by the athletic trainer, symptoms were limited to the right hand, and
      brachial plexus neurapraxia was diagnosed. DIFFERENTIAL DIAGNOSIS: Central cord
      syndrome, brachial plexus injury, cervical spine injury, burning hands syndrome,
      Brown-Sequard syndrome, anterior cord syndrome. TREATMENT: Upon assessment, the
      athlete's cervical spine was immobilized until emergency medical services arrived
      and applied a cervical collar. Radiographs taken at the hospital revealed a
      congenital fusion of C6-7. Magnetic resonance imaging and computed tomography
      showed evidence of stenosis, a herniated disc at C3-4, and a central cord injury.
      He was admitted to the hospital for observation and was placed on a
      corticosteroid protocol. At approximately 1 week after the injury, the athlete
      underwent a cervical decompression and fusion at C3-4. Subsequently, he underwent
      extensive rehabilitation and has had some persistent neck stiffness. The athlete
      is no longer allowed to participate in contact sports as a result of the presence
      of stenosis at multiple levels. UNIQUENESS: Central cord syndrome is typically
      seen in an older population with cervical spondylosis and rarely occurs in young
      adolescents. However, this athlete sustained 2 central cord injuries, 1 mild and
      1 severe, in less than 6 weeks' time. CONCLUSIONS: The original injury sustained
      by the wrestler was thought to be a brachial plexus injury but, in fact, was a
      mild central cord injury. Central cord syndrome was not suspected in the original
      injury because the athlete's complaint was of unilateral numbness. With the
      second injury, the central cord injury was more severe. Proper recognition,
      assessment, and handling of this situation were crucial in providing optimal care
      to this athlete.

PMID- 17043706
TI  - Management of overactive bladder with transdermal oxybutynin.
AB  - In clinical trials, transdermal oxybutynin (OXY-TDS) has shown comparable
      efficacy and improved tolerability when compared with conventional
      pharmacotherapy. Systemic anticholinergic adverse effects are comparable to those
      with placebo, most likely owing to avoidance of first-pass hepatic metabolism and
      conversion of oxybutynin to N-desethyloxybutynin. OXY-TDS has predictable
      pharmacokinetic absorption and elimination parameters, as shown in both in vitro
      and in vivo studies. Consistent plasma concentrations of oxybutynin avoid labile
      peak and trough concentrations seen with immediate-release formulations,
      paralleling extended-release drug delivery. This novel drug delivery system has
      unique dermatologic skin application site reactions, including erythema and
      pruritus. Skin reactions are usually mild and can be minimized by varying the
      site of patch application. Most eczematous dermatologic reactions can be
      appropriately treated with a moderately potent topical corticosteroid cream. A
      small percentage of patients will discontinue therapy as a result of bothersome
      application site skin reactions.

PMID- 17043707
TI  - New generation tissue sealants and hemostatic agents: innovative urologic
      applications.
AB  - Control of blood loss during urologic surgery is paramount to the success of
      patient recovery. Hemostatic agents and tissue sealants are used routinely to
      prevent excess blood loss and in reconstruction during surgical repair. Some of
      the available products include thrombin sealant, fibrin glue, bovine
      serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in
      mechanism, cost, and application. Complications can include allergic reactions or
      thromboembolism and the risk of contracting bovine spongiform encephalitis or
      hepatitis. Many new hemostatic agents are being developed and approved. The
      benefits and risks of use of these agents versus conventional treatment need to
      be considered on a case-by-case basis by the surgeon.

PMID- 17043708
TI  - The importance of pelvic lymph node dissection in men with clinically localized
      prostate cancer.
AB  - Despite advances in noninvasive staging, pelvic lymph node dissection (PLND)
      remains the most accurate means of detecting lymph node metastases in men with
      clinically localized prostate cancer. Nomograms exist that can identify patients
      at low risk for lymphatic metastases according to preoperative information. In
      general, it seems reasonable to omit PLND in men with a biopsy Gleason sum of 6
      or less and a prostate-specific antigen level of 10 ng/mL or less. Ultimately,
      however, this decision should be made according to physician and patient
      preference, considering the low contemporary morbidity associated with PLND. When
      PLND is performed, studies suggest that an extended dissection maximizes the
      detection rate of nodal involvement. Retrospective data indicate that an extended
      dissection might play a therapeutic role in a subset of patients with a limited
      lymph node burden. However, this might be an artifact of stage migration, and
      prospective studies are needed to evaluate this further.

PMID- 17043709
TI  - Best of the 2006 AUA Annual Meeting: Highlights from the 2006 Annual Meeting of
      the American Urological Association, May 20-25, 2006, Atlanta, GA.

PMID- 17043710
TI  - Spurious hypocalcemia after gadodiamide-enhanced magnetic resonance imaging: a
      case report and review of the literature.
AB  - Gadolinium-enhanced magnetic resonance imaging is a diagnostic modality widely
      used in urologic practice. We report on a 54-year-old woman in whom a critically
      low serum calcium level was measured with standard colorimetric assay after
      gadodiamide-enhanced magnetic resonance imaging. The same phenomenon was noted in
      2 other patients seen in our practice. Repeat serum calcium measurements
      performed several hours later were within normal limits. Commercially available
      gadolinium-based contrast agents might precipitate critically low serum calcium
      values when measured by standard colorimetric assay. Physician awareness of
      gadodiamide-induced spurious hypocalcemia might prevent unnecessary therapeutic
      interventions.

PMID- 17043711
TI  - Disappointing news for urologists managing interstitial cystitis patients.

PMID- 17043712
TI  - Probiotic therapy for hyperoxaluria.

PMID- 17043713
TI  - TESA or TESE: Which Is Better for Sperm Extraction?

PMID- 17043714
TI  - Recurrent pregnancy loss: who is to blame?

PMID- 17043715
TI  - Using spin polarised positive muons for studying guest molecule partitioning in
      soft matter structures.
AB  - Fully polarised positive muons substituted for protons in organic free radicals
      can be used as spin labels which reveal information about the structure, dynamics
      and environment of these radicals. In applications via the technique of avoided
      level-crossing muon spin resonance (ALC-microSR), the positive muon has been used
      to study the partitioning of phenyl alcohols in lamellar phase colloidal
      dispersions of a cationic dichain surfactant. Here we describe the experimental
      technique which permits highly sensitive spectroscopy as previously demonstrated
      for surfactant mixtures. We also demonstrate its capability in the study of
      partitioning of cosurfactant molecules in surfactant bilayers in order to
      elucidate the main factors which contribute to cosurfactant ordering at
      interfaces. The technique takes advantage of the positive muon combining with an
      electron to a hydrogen-like atom that is called muonium. This atom attaches to a
      phenyl group, forming a cyclohexadienyl-type radical that contains the muon as a
      polarised spin label, providing an excellent probe even for very low phenyl
      alcohol concentrations. The position of one type of resonance, which on the basis
      of spectroscopic selection rules is denoted as Delta(0), is related to the
      solvent polarity of the radicals' environment. The results derived from Delta(0)
      measurements reveal a systematic trend where the increasing chain length of the
      phenyl alcohol results in a deeper immersion of the phenyl ring of the alcohol
      into the surfactant bilayer with the OH group anchored at the interface. In
      addition, the data suggest partial penetration of water molecules into the
      bilayer. Furthermore, data ensuing from a second resonance (called Delta(1),
      which is dependent upon the degree of confinement of the radical within the
      surfactant aggregate structure) indicates not only that the phenyl alcohol
      resides in an anisotropic environment, (i.e. that the host molecule is unable to
      undergo full 3-D reorientation on a timescale of 50 ns), but the resonance line
      widths indicate that the radicals are undergoing fast rotation about a particular
      axis, in this instance about the first C-C substituent bond at the phenyl ring.
      Detailed analysis of these Delta(1) line shapes suggests that other types of
      motion involving reorientation of the above rotation axis are also present. At
      room temperature, the hydrocarbon chains of the double layers form an aggregate
      state commonly referred to as the L(beta) phase, where the motions of surfactant
      alkyl chains are effectively frozen out. These chains melt on heating over a
      temperature range which is solution composition dependent (ca. 51 to 67 degrees
      C), but in all cases leading to a liquid-like disordered hydrocarbon regime
      whilst retaining the overall lamellar structure (and in this state is termed
      L(alpha)). Above the L(alpha)/L(beta) chain ordering phase transition the tracer
      molecules reside within the bilayer, but below this transition (and depending on
      their water-oil solubility) they are completely or partly expelled. This
      interpretation is further supported by Heisenberg spin exchange experiments. The
      water-bilayer partitioning reflects both typical classical and nonclassical
      hydrophobic solvation depending on temperature and chain length of phenyl
      alcohols.

PMID- 17043716
TI  - Interfacial pH and surface pKa of a thioctic acid self-assembled monolayer.
AB  - A self-assembled acid-functionalised monolayer on a gold surface has an
      interfacial pH 2.93 more acidic than the bulk and surface pK(a) very similar to
      that of the free acid.

PMID- 17043717
TI  - Theoretical modeling and interpretation of X-ray absorption spectra of liquid
      water.
AB  - We report extensive calculations to examine the capability of theory to explain
      the XAS spectra of liquid water. Several aspects that enter the theoretical model
      are addressed, such as the quantum mechanical methods, the statistics and the XAS
      model. As input into our quantum mechanical calculations we will use structural
      information on liquid water obtained from first principles and from classical
      molecular dynamics simulations. As XAS models, we will examine the full core hole
      and the half core hole approximations to transition state theory. The quantum
      mechanics is performed on the basis of density functional theory. We conclude
      from this study that recent experimental results are fully consistent with, and
      can be completely explained by, present day theory, in particular, the pre-edge
      peak is reproduced. We also find that the average bond coordination in liquid
      water is 3.1 and that the assertion in a recent paper that the hydrogen bond
      number is much less than that cannot be substantiated. Our calculations emphasize
      that further advances in our understanding of water can only be made by more
      sophisticated spectroscopy with significantly increased resolution.

PMID- 17043718
TI  - Accurate potential energy curves for F(-)-Rg (Rg = He-Rn): spectroscopy and
      transport coefficients.
AB  - High-quality ab initio potential energy curves are presented for the F(-)-Rg
      series (Rg = He-Rn). Calculations are performed at the CCSD(T) level of theory,
      employing d-aug-cc-pV5Z quality basis sets, with "small core" relativistic
      effective core potentials being used for Kr-Rn. The quality of the curves is
      judged by agreement with recent high-level calculations in the case of F(-)-He
      and F(-)-Ne and by excellent agreement with mobility data for the systems F(-)-Rg
      (Rg = He-Xe). Except for these recent high-level calculations on the two lightest
      systems, we are able to deduce that all other previous potentials for the whole
      set of these systems are inadequate. We also present spectroscopic information
      for the titular species, derived from our potential energy curves.

PMID- 17043719
TI  - (2 + 1) REMPI spectroscopy of the NO-CO, NO-N2, and NO-{N(2), Ar} van der Waals
      complexes in the region of the 4s and 3d Rydberg states.
AB  - We have collected (2 + 1) Resonance-Enhanced Multiphoton Ionization (REMPI)
      spectra of van der Waals complexes in which a NO molecule is attached to either
      CO, N(2), or both N(2) and Ar. The energy region probed corresponds to electronic
      transitions of uncomplexed NO(X(2)Pi) to the 4s and 3d Rydberg states, and we
      discuss the observed spectra in light of the expected perturbations to these
      electronic levels induced by complexation. We employ a model in which the van der
      Waals partners are assumed to reside within the Rydberg orbital, and discuss the
      importance of core penetration in the description of the electronic structure. By
      performing calculations on NO(+) interacting with both N(2) and Ar, we identify
      the global minimum as being a non-planar structure. Further, the N(2) and Ar are
      found to interact with the NO(+) largely independently, and we find some evidence
      for this from the REMPI spectrum of NO-{N(2), Ar}.

PMID- 17043720
TI  - VUV electronic state spectroscopy of 1,1-difluoroethene and difluorochloromethane
      by high resolution synchrotron radiation.
AB  - High resolution VUV photoabsorption spectra of 1,1-difluoroethene (C(2)H(2)F(2))
      and difluorochloromethane (CF(2)HCl) are reported in the wavelength range 115-200
      nm (10.8-6.2 eV). New photoabsorption features are observed in C(2)H(2)F(2) and
      some Rydberg and vibrational assignments are proposed for the first time.
      Evidence for a weak vibrational pattern in CF(2)HCl is discussed here for the
      first time. Absolute cross section values have been obtained allowing photolysis
      lifetimes to be derived in the Earth's troposphere and stratosphere.

PMID- 17043721
TI  - Reactions of OH and NO radicals with 1,1-dichloroethylene in argon matrices. FTIR
      and theoretical studies.
AB  - HONO/1,1-dichloroethylene/Ar matrices were subjected to UV radiation (lambda >
      340 nm) from a medium pressure mercury lamp. The products of the photolysis were
      studied experimentally by means of FTIR spectroscopy and theoretically using the
      ab initio MP2 method. Two conformers of 2-nitroso-2,2-dichloroethanol molecule
      have been identified as the final products of the double addition reaction of the
      OH, NO radicals to 1,1-dichloroethylene. The additional reactive species observed
      in the matrix is tentatively identified as an 1,1-dichloro-2-hydroxyethyl
      radical, an intermediate formed by single addition of OH to 1,1-dichloroethylene.
      The three photoproducts have been identified and observed for the first time. The
      identities of the products have been justified by comparison with the experiments
      with deuterated DONO and by performing concentration and annealing studies as
      well as by reference to the spectral data of related molecules. The results of
      the quantum mechanical calculations confirmed both the assignment of the new
      molecules and mechanism of the reaction observed in our experiment.

PMID- 17043722
TI  - Hydration profiles of aromatic amino acids: conformations and vibrations of L
      phenylalanine-(H2O)n clusters.
AB  - IR-UV double resonance spectroscopy and ab initio calculations were employed to
      investigate the structures and vibrations of the aromatic amino acid, L
      phenylalanine-(H(2)O)(n) clusters formed in a supersonic free jet. Our results
      indicate that up to three water molecules are preferentially bound to both the
      carbonyl oxygen and the carboxyl hydrogen of L-phenylalanine (L-Phe) in a bridged
      hydrogen-bonded conformation. As the number of water molecules is increased, the
      bridge becomes longer. Two isomers are found for L-Phe-(H(2)O)(1), and both of
      them form a cyclic hydrogen-bond between the carboxyl group and the water
      molecule. In L-Phe-(H(2)O)(2), only one isomer was identified, in which two water
      molecules form extended cyclic hydrogen bonds with the carboxyl group. In the
      calculated structure of L-Phe-(H(2)O)(3) the bridge of water molecules becomes
      larger and exhibits an extended hydrogen-bond to the pi-system. Finally, in
      isolated L-Phe, the D conformer was found to be the most stable conformer by the
      experiment and by the ab initio calculation.

PMID- 17043723
TI  - Impact on lipid membrane organization by free branched-chain fatty acids.
AB  - Here, we exploit the non-invasive techniques of solid-state NMR (nuclear magnetic
      resonance) and differential scanning calorimetry (DSC) to study the effect of
      free iso and ante-iso branched chain fatty acids (BCFAs) on the physicochemical
      properties of lipid membranes. Free fatty acids are present in biological
      membranes at low abundance, but can influence the cellular function by modulating
      the membrane organization. Solid state NMR spectra of
      dimyristoylphosphatidylcholine (DMPC) lipid membranes containing either free 12
      methyltetradecanoic acid (a15:0) or free 13-methyltetradecanoic acid (i15:0),
      show significant differences in their impact on the lipid bilayer. Chain order
      profiles obtained by deuterium NMR on fully deuterated DMPC-d(67) bilayers
      revealed an ordering effect induced by both fatty acids on the hydrophobic
      membrane core. This behavior was also visible in the corresponding DSC
      thermograms where the main phase transition of DMPC bilayers-indicative of the
      hydrophobic membrane region-was shifted to higher temperatures, with the iso
      isomer triggering more pronounced changes as compared to the ante-iso isomer.
      This is probably due to a higher packing density in the core of the lipid
      bilayer, which causes reduced diffusion across membranes. By utilizing the
      naturally occurring spin reporters nitrogen-14 and phosphorus-31 present in the
      hydrophilic DMPC headgroup region, even fatty acid induced changes at the
      membrane interface could be detected, an observation reflecting changes in the
      lipid headgroup dynamics.

PMID- 17043724
TI  - HCl and DCl: a case study of different approaches for determining photo
      fractionation constants.
AB  - The photoabsorption cross sections of HCl and DCl are calculated using the
      reflection principle and time dependent wavepacket propagation methods. The
      absorption cross sections are compared to high precision experimental absorption
      cross sections from the literature and the different results given by the methods
      are discussed. The results of the calculations emphasize the important roles that
      photodissociation dynamics and the change in transition dipole moment with
      internuclear distance play in isotopic fractionation. The wave number dependent
      fractionation constants have been determined. The process fractionation constant
      has been calculated in the Venusian atmosphere where photo-fractionation leads to
      enrichment in deuterium through loss of hydrogen to space. At an altitude of 70
      km the process fractionation constant was found to be epsilon(p) = -344 per
      thousand and epsilon(p) = -256 per thousand for the experimental and the
      reflection principle methods, respectively. At the top of the atmosphere the
      process fractionation constant was evaluated to be epsilon(p) = -32 per thousand,
      epsilon(p) = -20 per thousand and epsilon(p) = -40 per thousand using the
      experimental data, the wavepacket and the reflection principle methods,
      respectively. Using the Rayleigh distillation formula it is concluded that HCl at
      the top of the Venusian atmosphere is fractionated (enriched in D) relative to
      the bulk composition prior to photolysis.

PMID- 17043725
TI  - Adsorption of CO2 on oxidized, defected, hydrogen and oxygen covered rutile (1 x
      1)-TiO2(110).
AB  - Presented are initial, S(0) and coverage, Theta, dependent S(Theta), adsorption
      probability measurements of CO(2) as a function of impact energy, E(i) = 0.12-1.3
      eV, adsorption temperature, T(s) = 85-300 K, hydrogen and oxygen pre-exposure, as
      well as density of defects, Gamma, as varied by annealing (T = 600-900 K) and
      Ar(+) ion sputtering (dose chi(Ar) at 600 eV at 85 K) of a rutile (1 x 1)
      TiO(2)(110) surface. The defect densities were qualitatively characterized by
      thermal desorption spectroscopy (TDS) of CO(2). The CO(2) TDS curves consisted of
      two structures that can be assigned to adsorption on pristine and oxygen vacancy
      sites, in agreement with earlier studies. S(0) decreased linearly with E(i) and
      was independent of T(s). The adsorption dynamics were dominated by the effect of
      precursor states leading to Kisliuk-like shapes over the E(i) and T(s) range
      studied. Oxygen vacancy sites reduced S(0) of CO(2). Preadsorbed oxygen blocked
      preferentially defect sites, which led to an increase in S(0). Hydrogen
      preadsorption results in physical site blocking with decreased S(0) as H
      preexposure increased, while the shape of S(Theta) curves was conserved. In
      contrast to oxygen, hydrogen does not adsorb preferentially on defect sites. The
      adsorption probability data were parameterized by analytic functions (Kisliuk
      model) and by Monte Carlo simulations (MCSs).

PMID- 17043726
TI  - Elucidation of the molecular structure of hydrated vanadium oxide species by X
      ray absorption spectroscopy: correlation between the V...V coordination number
      and distance and the point of zero charge of the support oxide.
AB  - The effect of the point of zero charge (PZC) of the support oxide (Al(2)O(3),
      Nb(2)O(5), SiO(2) and ZrO(2)) on the molecular structure of hydrated vanadium
      oxide species has been investigated with EXAFS spectroscopy for low-loaded
      vanadium oxide catalysts. It was found that the degree of clustering (i.e., the
      V[dot dot dot]V coordination number) and the V...V distance increase with
      decreasing PZC of the support oxide; i.e., Al(2)O(3) (8.7) < ZrO(2) (7) <
      Nb(2)O(5) (3.3) < SiO(2) (2). Upon hydration the silica-supported vanadium oxide
      exhibited a clear alteration in the position of the oxygen atoms surrounding the
      central vanadium atom and the number of oxygen atoms around vanadium increased to
      five. In contrast, only minor changes in the molecular structure were detected
      for the alumina-, niobia- and zirconia-supported vanadium oxide catalysts. Based
      on a detailed analysis of the EXAFS data a semi-quantitative distribution of
      vanadium oxide species present on the surface of the different support oxides can
      be obtained, which is in good agreement with earlier characterization studies
      primarily making use of Raman spectroscopy.

PMID- 17043728
TI  - PET with 18F-DOPA in the imaging of parathyroid adenoma in patients with primary
      hyperparathyroidism. A pilot study.
AB  - Preoperative localization of parathyroid adenomas (PA) can shorten operation time
      and improve curative rate; it becomes especially important in minimally invasive
      surgical techniques. AIM of this study was to investigate whether positron
      emission tomography (PET) with 3-,4-dihydroxy-6- (18) F-fluorophenylalanine (
      (18) F-DOPA), which showed very promising results in other neuroendocrine
      tumours, also helps to localize PA. PATIENTS, METHODS: Eight patients with proven
      primary hyperparathyroidism were studied preoperatively with PET. Seven also
      underwent scintigraphy with (99m) Tc-MIBI and ultrasonography of the neck. All
      patients were operated and the histological finding was used as a gold standard.
      RESULTS: All eight patients had a histologically proven PA. None of the PA showed
      any detectable uptake of (18) F-DOPA. However, ultrasonography detected 5/7 PA,
      scintigraphy detected 3/7 PA. CONCLUSION: These results suggest that PET with
      (18) F-DOPA is not useful in the detection of PA in patients with primary
      hyperparathyroidism.

PMID- 17043729
TI  - Gender dependent rate of metabolism of the opioid receptor-PET ligand
      [18F]fluoroethyldiprenorphine.
AB  - AIM: The morphinane-derivate 6-O-(2-[(18)F]fluoroethyl)-6-O
      desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opioid receptor ligand
      currently used in positron emission tomography (PET). Correction for plasma
      metabolites of the arterial input function is necessary for quantitative
      measurements of [(18)F]FDPN binding. A study was undertaken to investigate if
      there are gender dependent differences in the rate of metabolism of [(18)F]FDPN.
      METHODS: The rate of metabolism of [(18)F]FDPN was mathematically quantified by
      fitting a bi-exponential function to each individual's dynamic metabolite data.
      RESULTS: No statistically significant gender differences were found for age,
      weight, body mass index or dose. However, significant differences (p < 0.01) in
      two of the four kinetic parameters describing the rate of metabolism were found
      between the two groups, with women metabolizing [(18)F]FDPN faster than men.
      These differences were found in the contribution of the fast and slow kinetic
      components of the model describing the distribution of radioactive species in
      plasma, indicating a higher rate of enzyme-dependent degradation of [(18)F]FDPN
      in women than in men. CONCLUSION: The findings reinforce the need for
      individualized metabolite correction during [(18)F]FDPN-PET scans and also
      indicate that in certain cases, grouping according to gender could be performed
      in order to minimize methodological errors of the input function prior to kinetic
      analyses.

PMID- 17043730
TI  - Thallium-201 scan in evaluating thyroid nodules following equivocal fine-needle
      aspiration cytology.
AB  - The AIM of this prospective study was to evaluate the usefulness of the thallium
      201 ( (201) Tl) thyroid scan in the detection of malignancy in cold thyroid
      nodules whose status was equivocal following palpation fine-needle aspiration
      cytology (FNAC). PATIENTS, METHODS: Fifty-one patients with clinically palpable
      solitary cold thyroid nodules classified as non-diagnostic or suspicious
      following biopsy underwent (201) Tl thyroid scans. Each scan was performed 15 min
      (early scan) and 3 h (delayed scan) after an intravenous administration of 74 MBq
      (201) Tl. Thallium uptake in the nodules was visually assessed and scored on a
      three point scale, with a grade of three defining malignancy. All patients
      underwent surgery and the histopathology of nodule tissues were compared with
      results of the scans. RESULTS: Fifty-one nodules were examined. Forty were benign
      and 11 were malignant. For early scans, the diagnostically relevant parameters
      were: sensitivity (100%), specificity (75%), and accuracy (80%). Corresponding
      findings for the delayed scan were: 91%, 98%, and 96%. CONCLUSION: The (201) Tl
      scan is useful for detecting malignancy in cold thyroid nodules classified as
      nondiagnostic or suspicious lesions by FNAC.

PMID- 17043731
TI  - What is the best pre-therapeutic dosimetry for successful radioiodine therapy of
      multifocal autonomy?
AB  - PURPOSE: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies
      (MFA) is a problem as therapeutic outcome may be worse than in other kinds of
      autonomies. We compared different dosimetric concepts in our patients. PATIENTS,
      METHODS: Data from 187 patients who had undergone RIT for MFA (Marinelli
      algorithm, volumetric compromise) were included in the study. For calculation,
      either a standard or a measured half-life had been used and the dosimetric
      compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated
      by 2 alternative concepts and compared to therapeutic success achieved (concept
      of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based
      adaptation of target dose on total thyroid volume). RESULTS: If a standard half
      life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n
      = 143). If a measured half-life was used the success rate was 93.1% (13,6%
      hypothyroidism, n = 44). These differences were statistically not significant,
      neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid
      after therapy (ANOVA, all p > 0.05). The alternative dosimetric concepts would
      have resulted either in significantly lower organ doses (TcTUs-based calculation
      of autonomous volume; 80.76 +/- 80.6 Gy versus 125.6 +/- 46.3 Gy; p < 0.0001) or
      in systematic over-treatment with significantly higher doses (TcTUs-adapted
      concept; 164.2 +/- 101.7 Gy versus 125.6 +/- 46.3 Gy; p = 0.0097). CONCLUSIONS:
      TcTUsbased determination of the autonomous volume should not be performed, the
      TcTUs-based adaptation of the target dose will only increase the rate of
      hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for
      RIT of MFA. If so, individual therapeutic activities may be calculated based on
      thyroid size corrected to the 24h ITUs without using Marinelli's algorithm.

PMID- 17043732
TI  - Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging
      the intrathyroidal effective half-life of radioiodine. Useful or not?
AB  - AIM: Evaluation of intrathyroidal kinetics of radioiodine with and without
      lithium as adjunct with respect to the increase in radiation dose delivered to
      the thyroid. PATIENTS, METHODS: 267 patients in three groups were included in the
      study. Group I with 227 patients served as control group, Group II with 21
      patients and Group III with 19 patients were distinguished by an intrathyroidal
      half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group
      III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine
      therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by
      at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine
      were defined mathematically as balance of the thyroidal iodine intake and
      excretion by a two-compartment model. RESULTS: Under therapy the maximum uptake
      of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective
      half-life as well as the product of maximum uptake x effective half-life as an
      equivalent of radiation dose independent of thyroid volume was lowered in the
      same magnitude. In Group II, the energy-dose equivalent remained constant under
      therapy. With adjunct lithium in Group III, the effective half-life was prolonged
      significantly by factor 1.61 +/- 0.49 and the volume-independent energy-dose
      equivalent by factor 1.39 +/- 0.37. No severe side effects of lithium were
      observed. CONCLUSION: Using lithium as adjunct to radioiodine therapy increases
      the radiation dose delivered to the thyroid by 39% on average and nearly 30% of
      radioiodine activity can be saved in these patients. Lithium is recommended in
      patients with very short effective half-life in the diagnostic test in order to
      reduce the activity required and whole-body radiation dose.

PMID- 17043733
TI  - Combined 18F-FDG-PET/CT imaging of the head and neck. An approach to metal
      artifact correction.
AB  - PET/CT imaging is particularly promising for head/neck malignancies, but dental
      implants lead to biased CT attenuation and PET activity values following CT-based
      attenuation correction (CT-AC). OBJECTIVE: Here, we implement a metal artifact
      correction procedure (MAR) as part of the CT-AC for PET/CT imaging. RESULTS:
      Phantom studies indicate a maximum quantitative bias in CT and PET of 1000 HU and
      30 %, which is reduced to 230 HU and 6 %, respectively following MAR. These
      results were verified in selected patients. CONCLUSION: Artifacts and biases from
      dental implants can be reduced in PET/CT imaging by applying a simple MAR as part
      of the CT-AC.

PMID- 17043734
TI  - Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis.
AB  - Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an
      established concept for the treatment of persistent synovitis of the knee joint.
      The AIM of this study was to investigate the biological radiation effect on the
      basis of a characteristic radiation parameter. PATIENTS, METHODS: After RSO
      procedures with yttrium-90 citrate colloid and subsequent immobilisation of the
      knee, blood specimens of 10 patients were collected immediately before RSO and 11
      to 13 days after the intervention. The yield of dicentric chromosomes in the
      lymphocytes was determined exclusively in metaphases of the first cell cycle in
      vitro. In addition, activity leakage was measured by wholebody bremsstrahlung
      scintigraphy. RESULTS: No statistically significant increase in the number of
      dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192
      cells analyzed from the 20 blood samples could be found as a result of RSO.
      However, the analysis of at least 1000 cells per blood sample demonstrates a
      tendency for a biological radiation effect in the blood of patients on the basis
      of this characteristic radiation parameter. Two of the 10 RSO patients had
      undergone a second RSO using yttrium-90 citrate, whereby one patient displayed
      activity transport out of the knee joint, amounting to 6 MBq. Only for him a
      radiation effect (about 130 mGy per single RSO) could be calculated by biological
      dosimetry. CONCLUSION: Since in general, based on the analysis of dicentric
      chromosomes in at least 1000 lymphocytes per individual, detection limits for
      groups of persons after long-term exposures to low-LET radiation of 50-100 mGy
      are possible, we assume that RSO with yttrium-90 should be associated with a low
      whole-body radiation exposure.

PMID- 17043735
TI  - [Evil radioactivity. Subjective perception of radioactivity in patients with
      thyroid disease prior to treatment with radioiodine].
AB  - AIM: We assess the perspective of patients with thyroid disease towards radiation
      and radioactivity by means of a cultural-anthropological approach based on
      qualitative measures and quantitative scores. From the interviews with the
      patients we evaluate as to how much radioactivity is accepted as an abstract term
      or as a benefit within the medical context. PATIENTS, METHODS: 68 patients with
      autonomously functioning thyroid lesions (35 women, 33 men, 32-81 years) were
      included in this study. All patients were interviewed in an open dialogue with
      the principal investigator. Patients were asked to describe their attitude
      towards radioactivity in general and towards radioiodine therapy in particular.
      Patients were asked to use a scoring system (1 = positive, 5 = negative) to
      quantify their attitudes. RESULTS: The responses of all patients towards
      radioactivity in general were heterogeneous with most responses reflecting a
      negative perception. Many patients expressed their associated fears about atomic
      energy, malignant diseases and radioactive contamination. The scoring system
      reflected a mostly negative opinion base. However, patients became more positive
      once they assumed an immediate benefit of radioactivity for the treatment of
      their own disease (p = 0.01). CONCLUSIONS: Knowing about significant differences
      in patient's perception about radioactivity in general or in the clinical context
      may help to optimise and tailor the initial, pre-therapeutical interview towards
      the patient.

PMID- 17043736
TI  - Quantification of aortic valve stenosis in MRI-comparison of steady-state free
      precession and fast low-angle shot sequences.
AB  - We compared two different magnetic resonance (MR) sequences [steady-state free
      precession (SSFP) and gradient echo fast low-angle shot (FLASH)] for the
      assessment of aortic valve areas in aortic stenosis using transesophageal
      echocardiography (TEE) as the standard of reference. Thirty-two patients with
      known aortic stenosis underwent MR (1.5 T) using a cine SSFP sequence and a cine
      FLASH sequence. Planimetry was performed in cross-sectional images and compared
      to the results of the TEE. In seven patients the grade of stenosis was
      additionally assessed by invasive cardiac catheterization (ICC). The mean aortic
      valve area measured by TEE was 0.97+/-0.19 mm(2), 1.00+/-0.25 mm(2) for SSFP and
      1.25+/-0.23 mm(2) based on FLASH images. The mean difference between the valve
      areas assessed based on SSFP and TEE images was 0.15+/-0.13 cm(2) (FLASH vs TEE:
      0.29+/-0.17 cm(2)). Bland-Altman analysis demonstrated that measurements using
      FLASH images overestimated the aortic valve area compared to TEE. Comparing ICC
      with MRI and TEE, only a weak to moderate correlation was found (ICC vs TEE:
      R=0.52, p=0.22; ICC vs SSFP: R=0.20, p=0.65; ICC vs FLASH: R=0.16, p=0.70).
      Measurements of the aortic valve area based on SSFP images correlate better with
      TEE compared to FLASH images.

PMID- 17043737
TI  - Imaging oxygenation of human tumours.
AB  - Tumour hypoxia represents a significant challenge to the curability of human
      tumours leading to treatment resistance and enhanced tumour progression. Tumour
      hypoxia can be detected by non-invasive and invasive techniques but the inter
      relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM
      PET, and BOLD-MRI are the lead contenders for human application based on their
      non-invasive nature, ease of use and robustness, measurement of hypoxia status,
      validity, ability to demonstrate heterogeneity and general availability, these
      techniques are the primary focus of this review. We discuss where developments
      are required for hypoxia imaging to become clinically useful and explore
      potential new uses for hypoxia imaging techniques including biological conformal
      radiotherapy.

PMID- 17043738
TI  - Improved visualization of collateral ligaments of the ankle: multiplanar
      reconstructions based on standard 2D turbo spin-echo MR images.
AB  - The purpose of the study was to evaluate the visualization of the collateral
      ankle ligaments on multiplanar reconstructions (MPR) based on standard 2D turbo
      spin-echo images. Coronal and axial T2-weighted turbo spin-echo and MPR angled
      parallel to the course of the ligaments of 15 asymptomatic and 15 symptomatic
      ankles were separately analyzed by two musculoskeletal radiologists. Image
      quality was assessed in the asymptomatic ankles qualitatively. In the symptomatic
      ankles interobserver agreement and reader confidence was determined for each
      ligament. On MPR the tibionavicular and calcaneofibular ligaments were more
      commonly demonstrated on a single image than on standard MR images (reader 1: 13
      versus 0, P=0.002; reader 2: 14 versus 1, P=0.001 and reader 1: 13 versus 2,
      P=0.001; reader 2: 14 versus 0, P<0.001). The tibionavicular ligament was
      considered to be better delineated on MPR by reader 1 (12 versus 3, P=0.031). In
      the symptomatic ankles, reader confidence was greater with MPR for all ligaments
      except for the tibiocalcanear ligament (both readers) and the anterior and
      posterior talofibular ligaments (for reader 2). Interobserver agreement was
      increased with MPR for the tibionavicular ligament. Multiplanar reconstructions
      of 2D turbo spin-echo images improve the visualization of the tibionavicular and
      calcaneofibular ligaments and strengthen diagnostic confidence for these
      ligaments.

PMID- 17043739
TI  - Comparison of transperineal and transabdominal ultrasound in the assessment of
      voluntary pelvic floor muscle contractions and functional manoeuvres in continent
      and incontinent women.
AB  - Transperineal (TP) and transabdominal (TA) ultrasounds were used to assess
      bladder neck (TP) and bladder base (TA) movement during voluntary pelvic floor
      muscle (PFM) contraction and functional tasks. A sonographer assessed 60
      asymptomatic (30 nulliparous, 30 parous) and 60 incontinent (30 stress, 30 urge)
      women with a mean age of 43 (SD=7) years, BMI of 24 (SD=4) kg m2 and a median
      parity of 2 (range, 0-5), using both ultrasound methods. The mean of three
      measurements for bladder neck and bladder base (sagittal view) movement for each
      task was assessed for differences between the groups. There were no differences
      in bladder neck (p=0.096) or bladder base (p=0.112) movement between the four
      groups during voluntary PFM contraction but significant differences in bladder
      neck (p<0.004) and a trend towards differences in bladder base (p=0.068) movement
      during Valsalva and abdominal curl manoeuvre. During PFM contraction, there was a
      strong trend for the continent women to have greater bladder neck elevation
      (p=0.051), but no difference in bladder base movement (p=0.300), when compared to
      the incontinent women. The incontinent women demonstrated increased bladder neck
      descent during Valsalva and abdominal curl (p<0.001) and bladder base descent
      during Valsalva (p=0.021). The differences between the groups were more marked
      during functional activities, suggesting that comprehensive assessment of the PFM
      should include functional activities as well as voluntary PFM contractions. TP
      ultrasound was more reliable and takes measures from a bony landmark when
      compared to TA ultrasound, which lacks a reference point for measurements. TA
      ultrasound is less suitable for PFM measures during functional manoeuvres and
      comparisons between subjects. Few subjects were overweight so the results may not
      be valid in an obese population.

PMID- 17043740
TI  - Interrater reliability of assessing levator ani muscle defects with magnetic
      resonance images.
AB  - The objective of this study is to determine interrater reliability of assessing
      pubovisceral levator ani muscle defects with magnetic resonance images. Normal
      pubovisceral muscle was assigned a grade of 0; PVM defects were graded as mild=1
      (less than half missing), moderate=2 (more than half missing), and severe=3
      (total or near total loss). Among six pairs of examiners, percent agreement and
      weighted kappa coefficients were calculated to determine agreement between pairs
      of examiners and among all examiners (i.e., "overall"). For unilateral scoring,
      exact agreement was found in 83.7%, and differences of one, two, and three grades
      were found in 14.7, 1.5, and 0.1%, respectively. For bilateral scoring, exact
      agreement and differences of one, two and three grades were found in 75.4, 15.9,
      6.9, and 1.6%, respectively. Thus, exact agreement or a one-point difference was
      reached in 91.3% of cases. When defect status was categorized as none/normal,
      minor, and major, the overall weighted kappa coefficient was 0.86 (95% CI 0.83,
      0.89). There was variation among examiner pairs with unilateral (p=0.002) and
      bilateral (p=0.02) scoring, but not when defect status was categorized as
      none/normal, minor, and major (p=0.59). There was agreement to within one point
      in 91% of cases when six examiner pairs scored levator ani defects on a seven
      point scale. Examiner pairs discriminated injury similarly when defect status was
      categorized as normal/none, minor, or major.

PMID- 17043741
TI  - The impact of pregnancy and childbirth in the urethra of female rats.
AB  - The aim of this study was to evaluate the modifications in the amount of
      collagen, muscular, and elastic fibers in the mid-urethra of adult female rats
      during the pregnancy and after the natural childbirth, cesarean, and after
      simulated trauma of childbirth. The authors evaluated the histomorphometric
      aspects (collagen, muscular, and elastic fibers) in the mid-urethra of 70 animals
      distributed in seven groups: group 1 (n = 10)--control, group 2 (n = 10)-
      pregnant female rats, group 3 (n = 10)--female rats submitted to cesarean, group
      4 (n = 10)--female rats with natural childbirth, group 5 (n = 10)--virgin female
      rats with simulated trauma of childbirth, group 6 (n = 10)--female rats submitted
      to cesarean followed by simulation of childbirth trauma, and group 7 (n = 10)-
      female rats with natural childbirth followed by simulation of childbirth trauma.
      The average concentration of collagen and elastic fibers and the
      collagen/muscular fiber correlation in groups 1, 2, and 3 were similar and
      significantly inferior to groups 4, 5, 6, and 7. The average of muscular fibers
      was similar in groups 1, 2, and 3 and significantly superior to groups 4, 5, 6,
      and 7. Pregnancy and cesarean did not induce alterations in collagen, muscular,
      and elastic fibers. However, the vaginal delivery and simulation of childbirth
      trauma determined the decrease in muscular fibers and the increase in collagen
      and elastic fibers and the correlation collagen/muscular fiber.

PMID- 17043742
TI  - A genetic linkage map of Pacific white shrimp (Litopenaeus vannamei): sex-linked
      microsatellite markers and high recombination rates.
AB  - Pacific white shrimp (Litopenaeus vannamei) is the leading species farmed in the
      Western Hemisphere and an economically important aquaculture species in China. In
      this project, a genetic linkage map was constructed using amplified fragment
      length polymorphism (AFLP) and microsatellite markers. One hundred and eight
      select AFLP primer combinations and 30 polymorphic microsatellite markers
      produced 2071 markers that were polymorphic in either of the parents and
      segregated in the progeny. Of these segregating markers, 319 were mapped to 45
      linkage groups of the female framework map, covering a total of 4134.4 cM; and
      267 markers were assigned to 45 linkage groups of the male map, covering a total
      of 3220.9 cM. High recombination rates were found in both parental maps. A sex
      linked microsatellite marker was mapped on the female map with 6.6 cM to sex and
      a LOD of 17.8, two other microsatellite markers were also linked with both 8.6 cM
      to sex and LOD score of 14.3 and 16.4. The genetic maps presented here will serve
      as a basis for the construction of a high-resolution genetic map, quantitative
      trait loci (QTLs) detection, marker-assisted selection (MAS) and comparative
      genome mapping.

PMID- 17043743
TI  - Population structure of the boll weevil in cotton fields and subtropical forests
      of South America: a bayesian approach.
AB  - The main goal of this contribution is to investigate the genetic structure of
      boll weevil populations from South America (Argentina and Brazil) and to make
      further comparisons with a putative source population from USA. Samples were
      collected in a Paranaense forest under reserve protection, cotton fields and non
      cultivated areas. Data from anonymous molecular markers were analysed using both
      traditional methods of population genetics and Bayesian approaches. Results help
      to support a previous hypothesis on the presence of two lineages of boll weevil
      populations in South America: one with characteristics of recent invaders and the
      other with characteristics of ancient populations. The sample from Urugua-i
      Provincial Park (Misiones, Argentina) shows the highest percentage of polymorphic
      loci, the highest values of mean heterozigosity, and the largest number of
      population-specific alleles, all being typical features of ancient populations.
      Furthermore, the Urugua-i sample shows two gene pools occurring in sympatry,
      probably as a consequence of a secondary contact. The remaining samples reveal
      not only lower percentages of polymorphic loci and heterozygosity values, but
      also an almost negligible presence of specific alleles. Bayesian methods also
      suggest the occasional migration of some individuals of ancient lineages from
      their natural habitats in fragments of the Paranaense forest into cotton fields,
      and vice versa.

PMID- 17043744
TI  - Gene expression divergence and the origin of hybrid dysfunctions.
AB  - Hybrids between closely related species are often sterile or inviable as a
      consequence of failed interactions between alleles from the different species.
      Most genetic studies have focused on localizing the alleles associated with these
      failed interactions, but the mechanistic/biochemical nature of the failed
      interactions is poorly understood. This review discusses recent studies that may
      contribute to our understanding of these failed interactions. We focus on the
      possible contribution of failures in gene expression as an important contributor
      to hybrid dysfunctions. Although regulatory pathways that share elements in
      highly divergent taxa may contribute to hybrid dysfunction, various studies
      suggest that misexpression may be disproportionately great in regulatory pathways
      containing rapidly evolving, particularly male-biased, genes. We describe three
      systems that have been analyzed recently with respect to global patterns of gene
      expression in hybrids versus pure species, each in Drosophila. These studies
      reveal that quantitative misexpression of genes is associated with hybrid
      dysfunction. Misexpression of genes has been documented in sterile hybrids
      relative to pure species, and variation in upstream factors may sometimes cause
      the over- or under-expression of genes resulting in hybrid sterility or
      inviability. Studying patterns of evolution between species in regulatory
      pathways, such as spermatogenesis, should help in identifying which genes are
      more likely to be contributors to hybrid dysfunction. Ultimately, we hope more
      functional genetic studies will complement our understanding of the genetic
      disruptions leading to hybrid dysfunctions and their role in the origin of
      species.

PMID- 17043745
TI  - 1H, 13C, and 15N NMR assignment of the master Rep protein nuclease domain from
      the nanovirus FBNYV.

PMID- 17043746
TI  - Solution structure of calponin homology domain of Human MICAL-1.

PMID- 17043747
TI  - Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of
      metalloproteinase (TIMP) in cerebral cavernous malformations: immunohistochemical
      analysis of MMP-2, -9 and TIMP-2.
AB  - OBJECT: Hemorrhage from cerebral vascular malformations such as cerebral
      cavernous malformation (CCM) can result in significant mortality and morbidity,
      but its underlying mechanism is undetermined. Excessive degradation of the
      vascular matrix by matrix metalloproteinases (MMPs), proteolytic enzymes that
      degrade all the components of extracellular matrix, can lead to instability of
      the vascular structure and can thereby cause bleeding. Thus we examined the
      expression of MMPs and tissue inhibitors of metalloproteinase (TIMP) in CCM.
      PATIENTS AND METHODS: We performed immunohistochemistry for MMP-2, -9, and TIMP-2
      using Paraffin-embedded sections of the surgical specimens obtained from seven
      patients with CCM. All patients had a history of hemorrhage from CCM. FINDINGS:
      In all patients (7/7, 100%), MMP-2 and -9 were strongly expressed in endothelial
      cells of CCMs. Endothelial expression of TIMP-2 was also evident in all seven
      patients. In contrast, MMP-2, -9 and TIMP-2 were not identified in adjacent
      normal brain tissue. CONCLUSION: We found that CCM showed the increased
      endothelial expression of MMP-2, -9, and TIMP-2. Endothelial expression of MMPs
      and/or TIMP may affect the vascular matrix stability, and thus can contribute to
      hemorrhage from CCM.

PMID- 17043748
TI  - Ruptured intracranial aneurysm following gamma knife surgery for acoustic
      neuroma.
AB  - A-63-year-old woman underwent gamma knife surgery (GKS) for acoustic neuroma. Six
      years later, she suffered sudden onset of severe headache followed by a
      disturbance of consciousness and subarachnoid haemorrhage due to a ruptured
      aneurysm originating from the distal anterior inferior cerebellar artery. The
      aneurysm was not located at a branching site and was included within the
      radiation field. The aneurysm was treated by endovascular embolization, and now,
      15 months later, the patient has recovered satisfactorily. This is the first
      report of aneurysm formation following GKS for acoustic neuroma.

PMID- 17043749
TI  - Microsatellite analysis of Japanese sea cucumber, Stichopus (Apostichopus)
      japonicus, supports reproductive isolation in color variants.
AB  - The genetic relationship among the three color variants (Red, Green, and Black)
      of the Japanese sea cucumber, S. japonicus, was investigated using 11
      microsatellite markers. Genetic differentiation testing among the three sympatric
      color types showed the strong heterogeneity of Red (p<0.001), while no
      significant difference was observed between Green and Black (p=0.301 to 0.961).
      UPGMA trees constructed from 10 sample lots from 5 localities showed two distinct
      clusters, one from the Red types and the other from the Green and Black types. In
      addition, the sympatric Green and Black formed one subcluster with strong
      bootstrap support at each locality. These results indicate the separate species
      status of Red and the other color types, and also support the population identity
      of sympatric Green and Black.

PMID- 17043751
TI  - Prolonged anti-hypertensive effects of oral sitaxsentan, a selective ET(A)
      endothelin receptor antagonist, in spontaneoulsy hypertensive hamsters.
AB  - INTRODUCTION: The purpose of this study was to determine whether prolonged oral
      therapy with sitaxsentan, a potent selective ET(A) endothelin receptor
      antagonist, normalizes systolic blood pressure in spontaneously hypertensive
      hamsters, a new rodent model of high-renin genetic hypertension. MATERIALS AND
      METHODS: Spontaneously hypertensive hamsters received either oral sitaxsentan (15
      mg kg(-1) day(-1)) dissolved in high purity water or saline for 7 weeks. Systolic
      blood pressure was monitored in lightly anesthetized animals using the leg-cuff
      method. RESULTS: We found that sitaxsentan elicited a significant decrease in
      systolic blood pressure in spontaneously hypertensive hamsters from 175 +/- 6
      mmHg at baseline to 109 +/- 7 mmHg after 7 weeks (p < 0.05). Although treatment
      of spontaneously hypertensive hamsters with saline was also associated with a
      significant decrease in systolic blood pressure from baseline, the magnitude of
      response was significantly less than that observed with sitaxsentan (p < 0.05).
      DISCUSSION: Collectively, these proof-of-principle data indicate that prolonged
      oral sitaxsentan therapy normalizes systolic blood pressure in spontaneously
      hypertensive hamsters. We suggest that selective ET(A) endothelin receptor
      blockade could be beneficial in the treatment of essential hypertension
      associated with high renin plasma levels.

PMID- 17043750
TI  - Codon usage and selection on proteins.
AB  - Selection pressures on proteins are usually measured by comparing homologous
      nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a
      novel method, termed volatility, to estimate selection pressures on proteins on
      the basis of their synonymous codon usage (Plotkin and Dushoff 2003; Plotkin et
      al. 2004). Here we provide a theoretical foundation for this approach. Under the
      Fisher-Wright model, we derive the expected frequencies of synonymous codons as a
      function of the strength of selection on amino acids, the mutation rate, and the
      effective population size. We analyze the conditions under which we can expect to
      draw inferences from biased codon usage, and we estimate the time scales required
      to establish and maintain such a signal. We find that synonymous codon usage can
      reliably distinguish between negative selection and neutrality only for
      organisms, such as some microbes, that experience large effective population
      sizes or periods of elevated mutation rates. The power of volatility to detect
      positive selection is also modest--requiring approximately 100 selected sites-
      but it depends less strongly on population size. We show that phenomena such as
      transient hyper-mutators can improve the power of volatility to detect selection,
      even when the neutral site heterozygosity is low. We also discuss several
      confounding factors, neglected by the Fisher-Wright model, that may limit the
      applicability of volatility in practice.

PMID- 17043752
TI  - Activation dependent expression of MMPs in peripheral blood mononuclear cells
      involves protein kinase A.
AB  - Monocyte/Macrophages are integral cellular components of inflammation. Matrix
      metalloproteinases (MMPs) produced by these cells play a crucial role in every
      aspect of inflammation. Results of the investigations on activation dependent
      upregulation of MMPs in human peripheral blood mononuclear cells in culture using
      different lectins as an in vitro model system to mimic inflammatory monocytes are
      presented. Under normal physiological conditions the monocytes produced only very
      low amount of MMPs in an indomethacin insensitive PG/cAMP independent manner.
      Zymographic analysis and ELISA showed that treatment of monocyte with lectins
      like concanavalin A (ConA), wheat germ agglutinin (WGA) and Artocarpus lakoocha
      agglutinin (ALA) caused upregulation of MMPs and the maximum effect was produced
      by ALA. ALA significantly upregulated MMP-9 in a concentration and time dependent
      manner. Immunoblot analysis and RT-PCR confirmed ALA mediated upregulation of MMP
      9 production. Inhibition of ALA effect by indomethacin and reversal of the
      indomethacin effect by Bt(2)cAMP indicated involvement of cAMP dependent
      signaling pathway. Further support for the prostaglandin mediated effect was
      obtained by the upregulation of cyclooxygenase by ALA. H-89, an inhibitor of
      protein kinase A (PKA), inhibited the expression of MMP-9 indicating that ALA
      mediated upregulation of MMP-9 is mediated through PKA pathway. Increase in MMP
      production and increase in cyclooxygenase activity and inhibition of the effect
      of ALA on MMP production by indomethacin suggested that the ALA activated
      monocytes in culture can be used as an in vitro model system to study the
      intracellular signaling process involved in the mediation of inflammatory
      response.

PMID- 17043753
TI  - Prohibitin suppresses renal interstitial fibroblasts proliferation and phenotypic
      change induced by transforming growth factor-beta1.
AB  - Prohibitin (PHB), a potential tumor suppressor, has been shown to inhibit cell
      proliferation by repressing E2F-mediated transcription. But little is known about
      the role of PHB involved in tubulointerstitial fibrosis (TIF). Here, for the
      first time, we found PHB protein was positively expressed at normal renal
      tissues, strongly down-regulated in renal biopsy specimens, and negatively
      correlated with the expression of alpha-smooth-muscle actin (alpha-SMA) and with
      the degrees of tubulointerstitial lesions. Transforming growth factor-beta1 (TGF
      beta1) is the most important profibrotic cytokine in the process of TIF and
      capable of inducing cell phenotypic change of interstitial fibroblasts
      characterized by the de novo expression of alpha-SMA. Confocal microscopy showed
      majority of PHB is located at cytoplasm as well as at nucleus in rat kidney
      fibroblasts cell (NRK-49F). As we found that PHB protein and mRNA expression were
      down-regulated in NRK-49F cells following TGF-beta1 stimulation. We used
      transient transfection to over-express PHB protein and found that cells with
      increased PHB levels had a significant reduction in the percentage entering cell
      cycle and abolished de novo expression of alpha-SMA following TGF-beta1
      stimulation. Therefore, over-expression of PHB suppresses renal interstitial
      fibroblasts proliferation and cell phenotypic change induced by TGF-beta1, which
      indicates PHB as a potential therapeutic target to halt the progression of TIF.

PMID- 17043754
TI  - Cytological response of hemocytes in the European flat oyster, Ostrea edulis,
      experimentally exposed to mercury.
AB  - Molluscs bivalves have been widely used as bioindicators to monitor contamination
      levels in coastal waters. In addition, many studies have attempted to analyze
      bivalve organs, considered pollutant-targets, to understand the bio-accumulation
      process and to characterize the effects of pollutants on the organisms. Here we
      analyzed the effects of mercury exposure on flat oyster hemocytes. Optical and
      electronic microscope procedures were used to characterize hemocyte morphology.
      In addition, cell solutions treated with acridine orange were analyzed by flow
      cytometry and laser scanning cytometry in order to evaluate the variations of
      cytoplasmic granules (red fluorescence, ARF) and cell size (green fluorescence,
      AGF) of hemocyte populations over time. Light and electron microscopical studies
      enabled us to differentiate four hemocyte subpopulations, agranulocytes (Types I
      and II) and granulocytes (Types I and II). Slight morphological differences were
      observed between control and Hg-exposed cells only in granulocytes exposed to Hg
      for 30 days, where condensed chromatin and partially lysed cytoplasmic regions
      were detected. Flow and laser scanning cytometry studies allowed us to
      differentiate three hemocyte populations, agranulocytes (R1) and granulocytes (R2
      and R3). The exposure time to Hg increased the average red fluorescence (ARF) of
      agranulocytes and small granulocytes, while there was no change in large
      granulocytes, which showed a loss of membrane integrity. In control oysters, the
      three hemocyte populations showed an increase of ARF after 19 days of exposure
      although initial values were restored after 30 days. The average green
      fluorescence (AGF) was more stable than the ARF throughout the experiment. In Hg
      exposed oysters, the values of AGF of agranulocytes showed an increase at half Hg
      exposure period while the AGF values of large granulocytes decreased throughout
      the experiment, confirming the instability of these types of cells. The relative
      percentage of small granulocytes and granulocytes showed time variations in both
      control and exposed oysters. However, the values of small granulocytes remained
      constant during the whole experiment. The fact that there were only changes in
      agranulocytes and large granulocytes suggested a possible relationship between
      these two types of cells. In a quantitative study, we found a significant linear
      relationship between the agranulocytes and large granulocytes.

PMID- 17043755
TI  - [Stenting of the SFA--indications, techniques, results].
AB  - Aggressive risk factor modification, change of eating habits, exercise programs,
      and forceful antiplatelet therapy are the most important tools for the treatment
      of PAOD in symptomatic patients suffering from intermittent claudication. There
      are however no guidelines for revascularization at this stage. Endovascular
      treatment has been increasingly utilized over the last decade and increasingly
      displaced vascular surgery. Amongst numerous endovascular techniques beside PTA,
      stents meanwhile play the most important role due to constant technical progress.
      Results regarding the rate of restenosis or patency rates still remain worse
      compared to other vascular beds. This paper gives a review over recent results,
      currently available stent techniques, and possible indications for the
      endovascular therapy of an artery, which has turned out to be the biggest ordeal
      for material and construction of stents.

PMID- 17043757
TI  - Multiple intermediate conformations of jack bean urease at low pH: anion-induced
      refolding.
AB  - Structural and functional characteristics of jack bean urease (JBU), a hexameric
      enzyme having identical subunits, were investigated under neutral as well as
      acidic conditions by using CD, fluorescence, ANS binding and enzyme activity
      measurements. At low pH and low ionic strength, JBU exists in a partially
      unfolded state (U(A)-state), having predominantly beta structure and no tertiary
      interactions along with a strong ANS binding. Addition of salts like NaCl, KCl
      and Na(2)SO(4) to the U(A)-state induces refolding resulting in structural
      propensities similar to that of native hexamer. Moreover, at low concentrations,
      GuHCl behaves like an anion by inducing refolding of the U(A)-state. The anion
      induced refolded state (I(A)-state) is more stable than U(A)-state and the
      stability is nearly equal to that of the native protein against chemical-induced
      and thermal denaturation. Overall, these observations support a model of protein
      folding for a multimeric protein where certain conformations (ensembles of
      substates) of low energy prevail and populated under non-native conditions with
      different stability.

PMID- 17043758
TI  - Identification and characterization of a gamma-glutamyl transpeptidase from a
      thermo-alcalophile strain of Bacillus pumilus.
AB  - A gamma-glutamyltranspeptidase (GGT, E.C. 2.3.2.2) was isolated from a strain
      (A8) originating from Lake Bogoria (Kenya) and homologous with Bacillus pumilus.
      This GGT shows an optimal activity at pH 8.9 and 62 degrees C. The enzyme is
      thermostable up to 43 degrees C. The best reagent among the potential inhibitors
      was shown to be DON, which is an inhibitor highly specific for GGTs. Gly-Gly-Ala,
      Gly-Gly-Gly and Gly-Gly were identified as the best acceptors for the
      transpeptidation reactions catalyzed by the enzyme. The SDS-PAGE study revealed
      that the enzyme consists of two non-identical subunits (38,000 and 23,000). Only
      the large subunit was active when the enzyme was dissociated under denaturing
      conditions. The behavior of the native enzyme suggests that the active site of
      the large subunit is masked by the small subunit.

PMID- 17043759
TI  - Phylogenetic analysis of partial S1 and N gene sequences of infectious bronchitis
      virus isolates from Italy revealed genetic diversity and recombination.
AB  - A total of ten infectious bronchitis virus (IBV) isolates collected from
      commercial chickens in Italy in 1999 were characterized by RT-PCR and sequencing
      of the S1 and N genes. Phylogenetic analysis based on partial S1 gene sequences
      showed that five field viruses clustered together with 793/B-type strains, having
      91.3-98.5% nucleotide identity within the group, and one isolate had very close
      sequence relationship (94.6% identity) with 624/I strain. These two IBV types
      have been identified in Italy previously. The other three variant isolates formed
      novel genotype detected recently in many countries of Western Europe. For one of
      these variant viruses, Italy-02, which afterwards became the prototype strain,
      the entire S1 gene was sequenced to confirm its originality. In contrast,
      phylogenetic analysis of more conserved partial N gene sequences, comprising 1
      300 nucleotides, revealed different clustering. Thus, three variant IBVs of novel
      Italy-02 genotype, which had 96.7-99.2% S1 gene nucleotide identity with each
      other, belonged to three separate subgroups based on N gene sequences. 624/I-type
      isolate Italy-06 together with Italy-03, which was undetectable using S1 gene
      primers, shared 97.7% and 99.3% identity, respectively, in N gene region with
      vaccine strain H120. Only one of the 793/B-type isolates, Italy-10, clustered
      with the 793/B strain sharing 99.3% partial N gene identity, whereas the other
      four isolates were genetically distant from them (only 87.7-89.7% identity) and
      formed separate homogenous subgroup. The results demonstrated that both mutations
      and recombination events could contribute to the genetic diversity of the Italian
      isolates.

PMID- 17043760
TI  - Tumors in mice transgenic for the envelope protein of Jaagsiekte sheep
      retrovirus.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary
      adenocarcinoma (OPA), a contagious lung cancer in sheep. Previous studies have
      shown that the JSRV envelope protein (Env) functions as an oncogene, in that it
      can morphologically transform rodent fibroblast and epithelial cell lines. To
      obtain a small animal model for JSRV-induced OPA, we generated a transgene
      expressing an epitope-tagged JSRV Env under control of the lung-specific
      Surfactant Protein A (SPA) promoter. Transgenic mice containing the SPA-Env-HA
      transgene showed low efficiency but specific expression in the lung. F1 male
      progeny from one transgenic founder developed subdermal lipomas that expressed
      the transgene. These results indicate that the JSRV Env protein is capable of
      inducing tumors in transgenic mice, and in other cell types besides lung
      epithelial cells.

PMID- 17043761
TI  - Postmenopausal osteoporosis. What have we learned since the introduction of
      bisphosphonates?
AB  - Over the past 12 years bisphosphonates have become a mainstay of treatment for
      postmenopausal osteoporosis. As a class, bisphosphonates significantly suppress
      bone turnover and increase BMD at the lumbar spine and other site through their
      direct inhibitory effects on osteoclasts. Alendronate and risedronate reduce the
      incidence of clinical vertebral and non-vertebral fractures. Etidronate and both
      oral and intravenous ibandronate reduce the incidence of clinical vertebral
      fractures, but data from primary analyses for reduction in non-vertebral
      fractures are currently less robust. Intravenous administration of zoledronate is
      under late-stage investigation for use in postmenopausal osteoporosis.
      Combinations of alendronate with estrogen or raloxifene provide a greater
      reduction in bone turnover markers and greater increases in BMD, but fracture
      risk reduction has not been determined. Overall, bisphosphonates are well
      tolerated. The most common side effects of oral bisphosphonates are upper
      gastrointestinal symptoms. Newer safety concerns about the use of bisphosphonates
      include osteonecrosis of the jaw and oversuppression of bone turnover. The
      optimal duration of bisphosphonate treatment has not been clearly established.

PMID- 17043762
TI  - The use of parathyroid hormone in the treatment of osteoporosis.
AB  - Anabolic skeletal agents have recently broadened our therapeutic options for
      osteoporosis. By directly stimulating bone formation, they reduce fracture
      incidence by improving bone qualities in addition to increasing bone mass.
      Teriparatide [recombinant human parathyroid hormone(1-34)], the only anabolic
      agent currently approved in the United States for osteoporosis, has emerged as a
      major therapeutic approach to selected patients with osteoporosis. Teriparatide
      is approved for both postmenopausal women and men with osteoporosis who are at
      high risk for fracture. With the use of this anabolic agent, bone density and
      bone turnover increase, microarchitecture improves, and bone size is beneficially
      altered. The incidence of vertebral and nonvertebral fractures is reduced with
      teriparatide use. Combination therapy with parathyroid hormone and an
      antiresorptive does not appear to offer definitive advantages over the use of PTH
      or an antiresorptive alone, although recent ideas about combining these agents
      may offer new insights. In order to maintain increases in bone density acquired
      during PTH therapy, it is important to follow its use with an antiresorptive
      agent.

PMID- 17043764
TI  - The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and
      tumor-host interactions.
AB  - Interleukin-1 (IL-1) includes a family of closely related genes; the two major
      agonistic proteins, IL-1alpha and IL-1beta, are pleiotropic and affect mainly
      inflammation, immunity and hemopoiesis. The IL-1Ra antagonist is a physiological
      inhibitor of pre-formed IL-1. Recombinant IL-1alpha and IL-1beta bind to the same
      receptors and induce the same biological functions. As such, the IL-1 molecules
      have been considered identical in normal homeostasis and in disease. However, the
      IL-1 molecules differ in their compartmentalization within the producing cell or
      the microenvironment. Thus, IL-1beta is solely active in its secreted form,
      whereas IL-1alpha is mainly active in cell-associated forms (intracellular
      precursor and membrane-bound IL-1alpha) and only rarely as a secreted cytokine,
      as it is secreted only in a limited manner. IL-1 is abundant at tumor sites,
      where it may affect the process of carcinogenesis, tumor growth and invasiveness
      and also the patterns of tumor-host interactions. Here, we review the effects of
      microenvironment- and tumor cell-derived IL-1 on malignant processes in
      experimental tumor models and in cancer patients. We propose that membrane
      associated IL-1alpha expressed on malignant cells stimulates anti-tumor immunity,
      while secretable IL-1beta, derived from the microenvironment or the malignant
      cells, activates inflammation that promotes invasiveness and also induces tumor
      mediated suppression. Inhibition of the function of IL-1 by the IL-1Ra, reduces
      tumor invasiveness and alleviates tumor-mediated suppression, pointing to its
      feasibility in cancer therapy. Differential manipulation of IL-1alpha and IL
      1beta in malignant cells or in the tumor's microenvironment can open new avenues
      for using IL-1 in cancer therapy.

PMID- 17043763
TI  - New imaging technologies in the diagnosis of osteoporosis.
AB  - In the context of osteoporosis, bone quality--which encompasses trabecular and
      cortical micro-architecture, mass, and tissue mechanical & compositional
      properties--plays an important and as yet undiscovered role. Non-invasive
      assessment of bone quality has recently received considerable attention, as bone
      density alone has not been able to predict existing or future osteoporotic
      fractures, or to explain therapeutic effects of emerging treatments. The goal of
      this review, therefore, is to present imaging modalities and related analysis
      methods capable of assessing bone quality for improved diagnosis and care of
      osteoporotic individuals. The techniques described include quantitative
      ultrasound, quantitative computed tomography, peripheral quantitative tomography,
      micro computed tomography, magnetic resonance, radiographic texture analysis, as
      well as finite element analysis based on the above-mentioned imaging modalities.
      The performance of these techniques in predicting osteoporotic fracture and
      assessing strength indices are discussed.

PMID- 17043765
TI  - Web portal for management of bioindication methods and ecotoxicological tests in
      ecological risk assessment.
AB  - The objective of this article is to inform about efforts to design and implement
      a data model that can parametrically describe and store information about a wide
      range of ecotoxicological tests and bioindication methods used in Ecological Risk
      Assessment (EcoRA). At the same time it describes comprehensive web-based portal
      built on this model that can be used to quickly find relevant biological assays
      (ecotoxicological biotests) for given situation and therefore support the
      decision-making process in EcoRA. The model structure, features of the
      corresponding website and its current content is described in detail and proposed
      development and possible collaboration is outlined. The portal (DATEST) is
      located at http://projects.cba.muni.cz/datest. The aim of this work is to
      complement existing EcoRA decision-support tools with a web-based engine for
      storing and searching biological tests and methods used in EcoRA as there is
      currently no similar informational source available on the Internet.

PMID- 17043766
TI  - Signaling pathways mediating manganese-induced toxicity in human glioblastoma
      cells (u87).
AB  - Although essential, manganese (Mn) intake in excess leads to neurotoxicity. Mn
      neurotoxicity induces impairment of energy metabolism and ultimately cell death.
      Nevertheless, the signaling mechanisms underlying Mn toxicity are unknown.
      Employing human glioblastoma (U87) cells, we investigated several signaling
      pathways (ones promoting cellular proliferation and invasion) underlying Mn
      toxicity. Mn-treatment of U87 cells induced a down-regulation of MAPK pathway but
      the AKT pathway was not markedly affected. Mn-treatment of these cells induced
      decreases in their levels of c-Jun and c-Fos transcription factors and
      extracellular matrix degrading enzymes like MMP-2, which are associated with
      glioblastoma invasiveness. Mn-treatment also induced apoptosis in U87 cells.
      Thus, our results indicate that other than inducing apoptosis in U87 cells, Mn
      exerts differential effects on several signaling pathways promoting glioblastoma
      proliferation and invasion. Consequently, Mn may have pathophysiological roles in
      inducing apoptosis and in blocking glioblastoma invasion. Our results may thus
      have therapeutic implications.

PMID- 17043767
TI  - Acrylamide alters cytoskeletal protein level in rat sciatic nerves.
AB  - Occupational exposure and experimental intoxication with acrylamide (ACR) produce
      neuropathy characterized by nerve degeneration. To investigate the mechanism of
      ACR-induced neuropathy, male adult Wistar rats were given ACR (20, 40 mg/kg i.p.
      3 days/week) for 8 weeks. Sciatic nerves were Triton-extracted and centrifuged at
      a high speed (100,000 x g) to yield pellet and supernatant fractions. The
      contents of six cytoskeletal proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta
      tubulin, and beta-actin) in both fractions were determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results
      showed that the three neurofilament (NF) subunits (NF-L, NF-M, NF-H) in both the
      pellet and the supernatant fraction decreased significantly (P < 0.01) in the
      high-dosing group, except for NF-M in the pellet. alpha-tubulin, beta-tubulin,
      and beta-actin increased significantly in the supernatant (P < 0.01), whereas
      both alpha-tubulin and beta-tubulin decreased significantly in the pellet (P <
      0.01). However, beta-actin was not altered significantly in the sciatic nerves
      pellet. These findings suggest that ACR altered the cytoskeletal protein level in
      sciatic nerve, which may be one of the molecular mechanisms of ACR-induced
      peripheral neuropathy.

PMID- 17043769
TI  - Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells.
AB  - An increasing amount of evidence indicates that the disialoganglioside GD3 is
      involved in apoptosis in many cell lines. Our previous studies demonstrated that
      endogenous GD3 expression induced apoptosis in U-1242 MG glioma cells transfected
      with the GD3 synthase gene (U1242MG-GD3 cells). In this paper, we present further
      investigations on the molecular mechanisms of GD3-induced apoptosis in this cell
      line. We found that endogenously synthesized GD3 localizes to the caveolae of
      this cell line, where it promotes the localization of death receptor 5 (DR5),
      tumor necrosis factor receptor-1 (TNF-R1), and Fas (Apo-1) to the caveolae. In
      addition, caspase-8 was translocated to the caveolar fraction and cleaved; the
      cleaved proteins were then re-located into the high density fractions. However,
      GD3 had no effect on the distribution of the adapter protein Fas-associated death
      domain (FADD). We conclude that GD3 functions as a regulatory molecule early in
      the extrinsic apoptosis pathway.

PMID- 17043770
TI  - Skeletal muscle translocation in vertebrates.
AB  - It is now over 30 years since Bodo Christ first demonstrated that the musculature
      of the limb originated from the somites and overturned the then prevailing view
      that limb muscle develops from a local source. Subsequently, using electron
      microscopy and histological procedures, Bodo Christ identified that cells of the
      somites undergo an epithelial to mesenchymal transition which enabled them to
      move from their paraxial point of origin to distal locations. These studies
      defined this translocation as one of the major mechanisms allowing myogenic cells
      to translocate around the body. The other means used to translocate muscle
      involves the movement of cells as a sheet. The deployment of one of these two
      mechanisms has been postulated to be involved in the formation of all the
      hypaxial musculature of the vertebrate body. In this paper we describe the
      formation of muscles both in the head and in the body, which use a translocatory
      mechanism during their development. We highlight recent data showing that muscle
      translocation is a far more complex process than first thought but which in
      itself can be used as a valuable tool to address questions regarding tissue
      patterning and development.

PMID- 17043771
TI  - [Differential diagnosis of rheumatoid granuloma].
AB  - Rheumatoid granuloma (RG) is histomorphologically defined as a subcutaneous
      palisading granuloma with central fibrinoid necrosis. Clinically, it presents as
      a nodule typically localized at pressure points near the joints. From the
      rheumatic pathological point of view, the main diagnostic challenge is the
      differentiation of RG from granuloma anulare, especially if clinical information
      on the site of removal, known diseases, duration of illness, medication and
      existing American College of Rheumatology (ACR) criteria are missing. Other
      granulomatous lesions, such as mycobacterial infections, foreign body granulomas,
      necrobiosis lipoidica or sarcoidosis, can be differentiated from RG by
      histopathological criteria or by additional examinations such as pathogen
      specification or PCR. An immunohistochemical marker for the differential
      diagnosis of granulomas is not yet available. Diagnosis is based on conventional
      H-E staining, alcian blue-PAS staining, polarizing analysis or PCR. In the
      following article, the most important granulomatous entities in the differential
      diagnosis of RG are introduced and the main diagnostic characteristics are
      discussed.

PMID- 17043768
TI  - NO-cGMP signaling and regenerative medicine involving stem cells.
AB  - Nitric oxide (NO) is a short lived diatomic free radical species synthesized by
      nitric oxide synthases (NOS). The physiological roles of NO depend on its local
      concentrations as well as availability and the nature of downstream target
      molecules. At low nanomolar concentrations, activation of soluble guanylyl
      cyclase (sGC) is the major event initiated by NO. The resulting elevation in the
      intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse
      cellular and physiological processes. The participation of NO and cGMP in diverse
      physiological processes is made possible through cell type specific spatio
      temporal regulation of NO and cGMP synthesis and signal diversity downstream of
      cGMP achieved through specific target selection. Thus cyclic GMP directly
      regulates the activities of its downstream effectors such as Protein Kinase G
      (PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide
      phosphodiesterases, which in turn regulate the activities of a number of proteins
      that are involved in regulating diverse cellular and physiological processes.
      Localization and activity of the NO-cGMP signaling pathway components are
      regulated by G-protein coupled receptors, receptor and non receptor tyrosine
      kinases, phosphatases and other signaling molecules. NO also serves as a powerful
      paracrine factor. At micromolar concentrations, NO reacts with superoxide anion
      to form reactive peroxinitrite, thereby leading to the oxidation of important
      cellular proteins. Extensive research efforts over the past two decades have
      shown that NO is an important modulator of axon outgrowth and guidance, synaptic
      plasticity, neural precursor proliferation as well as neuronal survival.
      Excessive NO production as that evoked by inflammatory signals has been
      identified as one of the major causative reasons for the pathogenesis of a number
      of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases.
      Regenerative therapies involving transplantation of embryonic stem cells (ES
      cells) and ES cell derived lineage committed neural precursor cells have recently
      shown promising results in animal models of Parkinson disease (PD). Recent
      studies from our laboratory have shown that a functional NO-cGMP signaling system
      is operative early during the differentiation of embryonic stem cells. The cell
      type specific, spatio-temporally regulated NO-cGMP signaling pathways are well
      suited for inductive signals to use them for important cell fate decision making
      and lineage commitment processes. We believe that manipulating the NO-cGMP
      signaling system will be an important tool for large scale generation of lineage
      committed precursor cells to be used for regenerative therapies.

PMID- 17043772
TI  - [Bilateral serous detachment of the neurosensory retina and retinal pigment
      epithelium with rip of the peripheral pigment epithelium].
AB  - HISTORY: A 52-year-old patient with atypical plasmocytoma presented with a
      bilateral serous detachment of the retina as well as a huge detachment of the
      pigment epithelium (PE) in the periphery. Shortly thereafter the PE ruptured. In
      the left eye this led to substantial central macular fibrosis. DIAGNOSIS: The
      clinically healthy patient showed a nephrotic syndrome; neither typical
      monoclonality was detectable nor was erythropoiesis or myelopoiesis reduced.
      THERAPY: To avoid further reduction of VA pars plana vitrectomy (ppV) with
      silicone oil tamponade and laser coagulation was performed. Clinical findings
      were reduced significantly and VA was stabilized for 2.5 years. DISCUSSION: PE
      detachments and serous retinal detachments in patients with nephrotic syndrome
      are only mentioned in a few cases. However, a peripheral rupture of the PE to
      this extent seems to be very rare. Early ppV with silicone oil and laser
      coagulation may prevent further macular fibrosis.

PMID- 17043773
TI  - [Quality control in rehabilitation of patients with visual impairment: evaluation
      of use and benefits of optic and electronic devices].
AB  - BACKGROUND: Not only medical care and prescription of magnifying devices, but
      also social and professional rehabilitation are part of a complete
      interdisciplinary low vision service. This study provides quantitative data about
      the success of rehabilitation and the quality of the Low Vision Department's
      work. PATIENTS AND METHODS: A sample of 105 visually disabled patients, who had
      already been provided with magnifying aids and other rehabilitation measures by
      the Low Vision Department, answered a questionnaire about quality control during
      a follow-up visit. The survey was carried out between May and October 2004.
      Patients were asked to rate the different rehabilitation measures and to comment
      on how frequently they used the different magnifying devices. Furthermore, they
      were asked to judge to what degree they coped with different life situations when
      using or not using the low vision aids. RESULTS: The most frequently used aids
      were magnifiers (61%), glasses for near vision (34%), closed circuit television
      (20%), and monocular telescopes (20%). Of the 105 patients, 85 (81%) reported on
      frequent use of the devices, with just 3 patients (3%) reporting that they hardly
      ever used the aids. Only 2% of the patients could read newspaper text without the
      use of magnifying aids, while 51% were able to do this using the aids; 46% of the
      patients reported that they had profited from the social and professional
      rehabilitation measures. CONCLUSION: Independently from the causal ophthalmologic
      diagnosis, patients were found to have benefited greatly from the rehabilitation
      measures provided by the Low Vision Department, enabling them to take part in
      more activities and participate more fully in social life, thereby greatly
      improving their quality of life. Frequent use of the low vision aids by the
      patient was ensured when offered alongside continued professional support.

PMID- 17043774
TI  - A case of cytomegalovirus-associated multiple gastric ulcers in ulcerative
      colitis.

PMID- 17043775
TI  - Psychodynamic aspects of communication skills training: a pilot study.
AB  - GOALS OF WORK: Communication between patients and oncology clinicians is a key
      element of cancer care. Emotionally charged consultations may trigger clinicians'
      defense mechanisms, protecting them from painful emotions. Defense mechanisms,
      however, may also hamper the recognition of patients' suffering. This pilot study
      aims to explore clinicians' defense mechanisms observed in communication skills
      training (CST). PATIENTS AND METHODS: A verbatim transcription of videotaped
      interviews with simulated patients were evaluated before (N=10) and after CST
      (N=10) with the defense mechanism rating scales (DMRS). MAIN RESULTS: A wide
      variety of defense mechanisms were observed such as obsessional (e.g.
      intellectualisation) or disavowal (e.g. denial or projection). Immature defense
      mechanisms decreased after CST. CONCLUSIONS: A wide variety of defense mechanisms
      are operant in oncology clinicians facing challenging interviews with simulated
      patients. Defense mechanisms may be modified by CST.

PMID- 17043777
TI  - The expression of NK cell inhibitory receptors on cytotoxic T cells in B-cell
      chronic lymphocytic leukaemia (B-CLL).
AB  - Immune surveillance of tumours is mediated by cytotoxic T cells (CTL) that
      recognise tumour antigen. Reduced reactivity of CTL towards tumour cells could
      thus lead to disease progression and loss of tumour control. In B-cell chronic
      lymphocytic leukaemia (B-CLL), the function of tumour-reactive CTL seems to
      correlate inversely to disease stage. Inhibitory NK cell receptors are known to
      suppress the CTL response upon interaction with major histocompatibility complex
      (MHC) class I and increased expression of such receptors on CTL may inhibit the
      anti-tumour response. So, the aim of this study was to investigate the expression
      of NK cell inhibitory receptors on CTL in B-CLL patients and if such expression
      correlated to disease stage. CD8+ T cells from B-CLL patients in Binet stage A (n
      = 26) and stage C (n = 14) and healthy controls (n = 14) were analysed for the
      expression of killer immunoglobulin-like receptors (KIR) CD158a (KIR2DL1), CD158b
      (KIR2DL2), CD158e (KIR3DL1) and the C-type lectin receptor CD94, by flow
      cytometry analysis. Patients with advanced disease (Binet stage C) had a
      significantly greater percentage of CTL expressing CD158b, CD158e and CD94 than
      patients with non-progressive disease (Binet stage A) and healthy controls. Stage
      C patients also had a significantly higher percentage of CTL expressing CD158a
      than stage A patients. No statistically significant differences were found
      between Binet A patients and healthy controls. Our results suggest that increased
      expression of KIR and CD94 on CTL in advanced stage B-CLL may potentially
      contribute to the impaired anti-tumour immune response in these patients.

PMID- 17043778
TI  - Small-bowel perforation accompanied by Aspergillus endocarditis in a patient with
      angioimmunoblastic T-cell lymphoma.

PMID- 17043776
TI  - Life after cancer: couples' and partners' psychological adjustment and supportive
      care needs.
AB  - GOALS OF WORK: Partners of cancer patients may experience significant distress at
      the time of treatment and many may experience persistent difficulties, although
      little research has examined their longer term psychosocial outcomes or
      supportive care needs. MATERIALS AND METHODS: One hundred and fifty-four cancer
      survivors who were 1-11 years post diagnosis and disease-free and their partners
      completed mailed questionnaires. MAIN RESULTS: A positive relationship was found
      between psychological distress and supportive care needs both within and between
      partner and survivor samples. Partners reported high levels of anxiety and
      supportive care needs, most frequently concerning relationships and the impact of
      the cancer illness. Partners within couples reported both shared and unique
      needs, although agreement on ratings of shared needs was low. Needs did not
      diminish over time although partners demonstrated psychological resilience and
      reported positive outcomes. Predictors of distress and unmet needs were explored:
      physical QOL, relationship satisfaction, and total needs contributed to
      variability in partners' distress; relationship satisfaction and total needs were
      associated with survivors' distress. Distress and relationship satisfaction were
      associated with partners' unmet needs; only distress was associated with
      survivors' unmet needs. CONCLUSIONS: Partners are not merely providers of
      support, but need support themselves many years after a cancer diagnosis and in
      the context of apparently cured disease. The quality of the dyadic relationship
      may be critical in determining both partner and survivor distress and needs, and
      may prove a useful target for psychosocial interventions.

PMID- 17043779
TI  - Association of homocysteine, vitamin B12, folic acid, and MTHFR C677T in patients
      with a thrombotic event or recurrent fetal loss.
AB  - Hyperhomocysteinemia (HHC) is a known risk factor for venous and arterial
      thrombosis. Thrombophilia workup includes the level of homocysteine and other
      related parameters such as: vitamin B(12), folic acid, and
      methylenetetrahydrofolate reductase (MTHFR) C677T genotype. As the levels of
      homocysteine, vitamin B(12), folic acid, and MTHFR C677T genotype are linked
      biochemically, we hypothesized that a statistical association will be found
      between them. The purpose of the present study was to assess the association
      between the four parameters in patients with a thrombotic event or recurrent
      fetal loss. The potential study population included 326 patients who were
      referred to the Thrombosis and Hemostasis Unit; 125 of these patients had at
      least one pathological test result of the four parameters. The correlations
      between homocysteine and vitamin B(12) as well as between homocysteine and folic
      acid were found to be weak (r = -0.236 and r = -0.209, respectively). No
      significant difference was revealed between the mean homocysteine level and the
      CC, CT, and TT MTHFR genotypes (p = 0.246). In conclusion, in the population
      studied, the association between homocysteine, vitamin B(12), folic acid, and
      MTHFR C677T is weak. The results raise doubt as to whether the current routine
      evaluation of HHC, as part of thrombophilia workup, truly reflects the increased
      risk of thrombosis.

PMID- 17043780
TI  - Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome
      in a xenogenic transplant model.
AB  - It has been suggested that human mesenchymal stem cells (hMSC) could be used to
      repair numerous injured tissues. We have studied the potential use of hMSC to
      limit radiation-induced skin lesions. Immunodeficient NOD/SCID mice were locally
      irradiated to the leg (30 Gy, dose rate 2.7 Gy/min) using a (60)Co source to
      induce a severe skin lesion. Cultured bone marrow hMSC were delivered
      intravenously to the mice. The irradiated skin samples were studied for the
      presence of the human cells, the severity of the lesions and the healing process.
      Macroscopic analysis and histology results showed that the lesions were evolving
      to a less severe degree of radiation dermatitis after hMSC transplant when
      compared to irradiated non-transplanted controls. Clinical scores for the studied
      skin parameters of treated mice were significantly improved. A faster healing was
      observed when compared to untreated mouse. Immunohistology and polymerase chain
      reaction analysis provided evidence that the human cells were found in the
      irradiated area. These results suggest a possible use of hMSC for the treatment
      of the early phase of the cutaneous radiation syndrome. A successful transplant
      of stem cells and subsequent reduction in radiation-induced complication may open
      the road to completely new strategies in cutaneous radiation syndrome therapy.

PMID- 17043781
TI  - [Increased levels of auto-antibodies in thyroid diagnostics: Hashimoto
      thyroidities or Graves disease?].

PMID- 17043782
TI  - [Avulsion injury to the posterior horn of the lateral meniscus. Technique for
      arthroscopic refixation].
AB  - An avulsion of the posterior tibial insertion of the meniscus (root tear) is a
      rare clinical diagnosis. Yet, due to the inconsistent clinical symptoms and the
      difficult arthroscopic assessment, an injury to the root of the meniscus can be
      easily missed. We present a possible technique for arthroscopic management of
      root tears using a tibial tunnel approach. A possible injury mechanism could be a
      rotational distortion of the knee. Another mechanism of injury is an overly
      posterior tunnel placement in ACL reconstruction. The clinical assessment of the
      lesion is based on thorough arthroscopic diagnosis of the lateral posterior horn
      in the figure of 4 position. A tibial ACL aimer can be used to locate a K-wire in
      the anatomical footprint of the posterior root of the meniscus. After
      overdrilling using a 4.5-mm drill, two sutures can be passed through the meniscal
      tissue and the sutures can be pulled out of the tibial tunnel. Extracortical
      fixation can be used by tying the sutures over a button.A root tear of the
      meniscus is a difficult clinical and arthroscopic diagnosis. A possibility for
      refixation of this lesion is to use a tibial tunnel technique. An associated
      injury to the ACL facilitates the tunnel placement and the suture management.

PMID- 17043784
TI  - [Rotating platform spinout in LCS knee arthroplasty].
AB  - In knee arthroplasty, a lax flexion gap may cause flexion instability.
      Subsequently, the operated knee may subluxate or dislocate. We report on a case
      of recurrent subluxations with malrotation of the rotating platform (spinout)
      after primary LCS total knee arthroplasty. Potential causes for spinout, therapy
      procedures, and consequences for the primary surgical technique are discussed. In
      the LCS rotating platform knee arthroplasty, the flexion gap must not be laxer
      than the extension gap. In such an instance, we recommend a higher rotating
      platform and a more proximal distal transverse femoral osteotomy.

PMID- 17043783
TI  - [Combined latissimus dorsi-thoracodorsal artery perforator-transpositional free
      flap].
AB  - BACKGROUND: Reconstruction or complete cover of extended but polygonal defects is
      limited by the size of transplantable tissue. One of the largest composite tissue
      components to be transplanted is the myocutaneous latissimus dorsi flap. Under
      certain circumstances even this large-scale flap is not sufficient for complete
      defect cover. Based on experiences with the thoracodorsal artery perforator (TAP)
      flap, the skin island adjacent to the latissimus muscle may be raised, pedicled
      on the perforator vessels penetrating the underlying muscle. Thus this island may
      easily be transposed or rotated to enable additional defect cover. METHODS: This
      method was applied in eight patients for defect cover at the extremities, thorax
      or for hypopharynx reconstruction. The exact location of perforator vessels may
      be determined pre- or intraoperatively with a hand Doppler so that skin flap
      transposition can already be planned before surgery. RESULTS: All of the skin
      flaps transposed or rotated healed without complications. It may even be assumed
      that utilizing this method helped to avoid further complications like scar
      contractures, because tension-free wound closure was feasible. CONCLUSIONS: The
      combined latissimus dorsi- thoracodorsal artery perforator-transpositional free
      flap is capable of covering very extensive polygonal as well as defects over
      joints in order to prevent scar contractions.

PMID- 17043785
TI  - [Adrenalectomy after snowboard fall. A pheochromocytoma becomes clinically
      apparent in an unusual way].
AB  - A 33-year-old snowboarder fell and underwent radiological examination, which was
      suspicious for a vertebral body fracture. Accidentally we found a tumour of the
      left suprarenal gland. Two days after the fall, he developed a hypertensive
      crisis with peak blood pressure levels up to 280/120 mmHg. Further endocrinologic
      testing indicated a pheochromocytoma which was confirmed by post-operative
      histology. The fall is supposed to have activated the pheochromocytoma. The
      course of examinations and significance of the tumour are described.

PMID- 17043786
TI  - [Spinal epidural empyema. Limited surgical treatment combined with continuous
      irrigation and drainage].
AB  - Epidural empyema of the spinal column is a rare, but in some cases devastating,
      disease. Surgery can be excessive or very limited. We want to report our results
      of combined therapy of limited surgical treatment and continuous irrigation with
      antibiotic solution and drainage. In the last 5 years we have operated on 12
      patients (7 female, 5 male, median age: 61.5 years, range: 22-89 years) with
      spinal epidural empyema. All surviving patients were evaluated after 3 months
      including MRI. Six infections were caused by injections, two by spontaneous
      discitis, two by chronic systemic infections, and in two patients the cause
      remained unknown. In every case we implanted two catheters, one for irrigation
      with antibiotic solution and one for drainage. On average the catheters were used
      for 3 days. For evacuation in seven patients interlaminar fenestration in one,
      two, or three levels was enough. Only in one patient was a laminectomy performed.
      Five patients recovered totally, three partially, one did not recover at all, and
      three died. The autopsy of two dead patients showed complete healing of the
      operated area; they died because of lethal infections in other parts of their
      body. In only one case did a reoperation have to be done. The cause was an
      additional subdural empyema. In spite of the limited surgical procedure without
      relevant operative morbidity the reported method is an effective and safe
      therapy.

PMID- 17043787
TI  - [Autologous chondrocyte transplantation by the sandwich technique. A salvage
      procedure for osteochondritis dissecans of the knee].
AB  - The case presented is that of a 23-year-old man suffering from osteochonditis
      dissecans (OCD) of the medial femoral condyle, in whom a free piece of cartilage
      had separated off and there was a large osteochondral defect despite numerous
      operations. After refixation of the fragment failed, an autologous chondrocyte
      transplantation (ACT) was performed using the sandwich technique. Three years
      after the operation the patient is very satisfied with the result. The
      radiological findings show stable repair of the bony and cartilaginous defect
      area. This case report shows that ACT is a valid method for the treatment of
      large osteochondral defects even after several previous failed operations. The
      low donor site morbidity is an important advantage over other methods, such as
      transplantation of osteochondral plugs.

PMID- 17043788
TI  - [Defect of the femoral condyle in the knee after patellectomy. Long-term results
      of fresh massive osteochondral allografting].
AB  - The presence of a massive full-thickness osteochondral defect in the knee of
      young and active individuals is an unsolved problem in orthopedic surgery,
      especially in post-traumatic large bone defects. Fresh massive osteochondral
      allografts have been used for many years but mostly in oncology but not in post
      traumatic cases. This case report describes a 20-year-old right leg-dominant
      woman, who, at age 19, sustained open Gustilo-Anderson type III comminuted
      fractures of the left patella and lateral femoral condyle in a motorbike
      accident. Initial treatment included immediate debridement and patellectomy with
      lavage. The large defect of the femoral condyle was reconstructed with a massive
      osteochondral allograft 1 year after the injury. The graft was obtained from our
      institutional tissue bank. The damaged bearing part of the condyle was resected
      to bleeding bone to create the nearly rectangular defect. The central condyle
      wall remained intact. The graft was trimmed to fit the defect and fixed with
      three cancellous 6.5-mm screws. The meniscus was not damaged. Partial weight
      bearing was permitted at 8 weeks and full weight bearing at 16 weeks after the
      surgery. At the last follow-up control 10 years after the surgery, no evidence of
      tibiofemoral arthrosis was present. The allograft-host interface was not visible.
      The radiodensity of the graft was nearly identical to the host bone. The Lysholm
      score and clinical findings were identical (100 points) to those 18 months after
      the surgery. The patient was extremely satisfied without complaints at 30 years
      of age.

PMID- 17043789
TI  - [Is use of the fixateur externe no longer indicated for the treatment of unstable
      radial fracture in the elderly?].
AB  - BACKGROUND: In recent years there has been an increasingly marked shift in the
      operative treatment of unstable fractures of the distal radius. The introduction
      of locking compression plates has made it possible to extend the indications for
      palmar stabilisation according to the principles of internal fixation to
      extension fractures even in osteoporotic bone, and since then the new design has
      been used more and more widely. First clinical results show very good and good
      clinical and radiological outcomes in over 80% of cases after locking compression
      plate osteosynthesis. All this raises the question of whether external fixation
      is no longer indicated for distal radius fractures in the elderly, or is now no
      more than a second-line treatment. PATIENTS AND METHODS: Within a 5-year period,
      67 patients over 65 years of age were identified among 220 who had had unstable
      fractures of the distal radius in our hospital with external fixation. The
      average follow-up period (clinical and radiological examinations) was 37 months.
      We devoted particular attention to the analysis of complications and problems
      during the treatment. RESULTS: Complete bone healing was observed in all patients
      treated with external fixation. In most cases, complications were minor pin-track
      infections (10%). The radiological follow-up examination revealed radial
      shortening by an average of 2 mm and an average radial shift of 0.2 mm. The joint
      angle was 2.5 degrees with lateral irradiation and 18 degrees with dorso-palmar
      irradiation. According to the Gartland and Werley score, the functional,
      radiological and subjective outcome was excellent or good in 87% of these
      patients. CONCLUSIONS: Overall, internal fixation with angular fixed plates has
      definite benefits. The medium- and long-term follow-up and functional outcome
      still show no benefits over external fixation, however. External fixation is a
      genuine option, even if as second-line treatment.

PMID- 17043790
TI  - [Flexor tendon rupture after palmar osteosynthesis using a multidirectional fixed
      angle plate].
AB  - Six months after the internal fixation of a distal intra-articular fracture of
      the radius with a fixed-angle plate (APTUS by Medartis), a 79 year old woman
      sustained chronic tears in flexor digitorum profundus tendons II, III and the
      flexor pollicis longus tendon.

PMID- 17043791
TI  - Heterogeneity of dendritic cells in rat apical periodontitis.
AB  - Dendritic cells are important for the induction of T-lymphocyte-mediated immunity
      by acting as antigen-presenting cells. We have previously reported that dendritic
      cells are prevalent in the chronic non-expanding phase of rat apical
      periodontitis. To characterize these cells further, immunoelectron microscopy
      with three dendritic cell markers (CD11c, OX6, OX62) was conducted for samples
      from rat models of apical periodontitis. Dendritic cells were divided into two
      types (type I or type II). Most of the type I dendritic cells expressed CD11c,
      showed an irregular large profile, had typical cytoplasmic processes, and were
      recognized as the major dendritic cell population. Most of the type II dendritic
      cells expressed OX62, showed oval small profiles with a few thin short processes,
      and were sometimes observed infiltrating from blood vessels. Cell-to-cell
      contacts between type I dendritic cells and lymphocytes were the most frequently
      observed associations. These results suggest that dendritic cells are composed of
      heterogeneous populations that exhibit different phenotypes, morphologies, and
      maturation/differentiation/activation.

PMID- 17043792
TI  - Dermal matrix proteins initiate re-epithelialization but are not sufficient for
      coordinated epidermal outgrowth in a new fish skin culture model.
AB  - We have established a new culture system to study re-epithelialization during
      fish epidermal wound healing. In this culture system, fetal bovine serum (FBS)
      stimulates the epidermal outgrowth of multi-cellular layers from scale skin
      mounted on a coverslip, even when cell proliferation is blocked. The rate of
      outgrowth is about 0.4 mm/h, and at 3 h after incubation, the area occupied by
      the epidermal sheet is nine times larger than the area of the original scale
      skin. Cells at the bottom of the outgrowth show a migratory phenotype with
      lamellipodia, and "purse string"-like actin bundles have been found over the
      leading-edge cells with polarized lamellipodia. In the superficial cells, re
      development of adherens junctions and microridges has been detected, together
      with the appearance and translocation of phosphorylated p38 MAPK into nuclear
      areas. Thus, this culture system provides an excellent model to study the
      mechanisms of epidermal outgrowth accompanied by migration and re
      differentiation. We have also examined the role of extracellular matrix proteins
      in the outgrowth. Type I collagen or fibronectin stimulates moderate outgrowth in
      the absence of FBS, but development of microridges and the distribution of
      phosphorylated p38 MAPK are attenuated in the superficial cells. In addition, the
      leading-edge cells do not have apparent "purse string"-like actin bundles. The
      outgrowth stimulated by FBS is inhibited by laminin. These results suggest that
      dermal substrates such as type I collagen and fibronectin are able to initiate
      epidermal outgrowth but require other factors to enhance such outgrowth, together
      with coordinated alterations in cellular phenotype.

PMID- 17043794
TI  - Regeneration in Macrostomum lignano (Platyhelminthes): cellular dynamics in the
      neoblast stem cell system.
AB  - Neoblasts are potentially totipotent stem cells and the only proliferating cells
      in adult Platyhelminthes. We have examined the cellular dynamics of neoblasts
      during the posterior regeneration of Macrostomum lignano. Double-labeling of
      neoblasts with bromodeoxyuridine and the anti-phospho histone H3 mitosis marker
      has revealed a complex cellular response in the first 48 h after amputation; this
      response is different from that known to occur during regeneration in triclad
      platyhelminths and in starvation/feeding experiments in M. lignano. Mitotic
      activity is reduced during the first 8 h of regeneration but, at 48 h after
      amputation, reaches almost twice the value of control animals. The total number
      of S-phase cells significantly increases after 1 day of regeneration. A
      subpopulation of fast-cycling neoblasts surprisingly shows the same dynamics
      during regeneration as those in control animals. Wound healing and regeneration
      are accompanied by the formation of a distinct blastema. These results present
      new insights, at the cellular level, into the early regeneration of
      rhabditophoran Platyhelminthes.

PMID- 17043793
TI  - Distribution of phosphorylated protein kinase C alpha in goldfish retinal bipolar
      synaptic terminals: control by state of adaptation and pharmacological treatment.
AB  - Protein kinase C (PKC) is a signalling enzyme critically involved in many aspects
      of synaptic plasticity. In cyprinid retinae, the PKC alpha isoform is localized
      in a subpopulation of depolarizing bipolar cells that show adaptation-related
      morphological changes of their axon terminals. We have studied the subcellular
      localization of phosphorylated PKC alpha (pPKC alpha) in retinae under various
      conditions by immunohistochemistry with a phosphospecific antibody. In dark
      adapted retinae, pPKC alpha immunoreactivity is weak in the cytoplasm of synaptic
      terminals, labelling being predominantly associated with the membrane
      compartment. In light-adapted cells, immunoreactivity is diffusely distributed
      throughout the terminal. Western blot analysis has revealed a reduction of pPKC
      alpha immunoreactivity in cytosolic fractions of homogenized dark-adapted retinae
      compared with light-adapted retinae. Pharmacological experiments with the isoform
      specific PKC blocker Goe6976 have shown that inhibition of the enzyme influences
      immunolabelling for pPKC alpha, mimicking the effects of light on the subcellular
      distribution of immunoreactivity. Our findings suggest that the state of
      adaptation modifies the subcellular localization of a signalling molecule (PKC
      alpha) at the ribbon-type synaptic complex. We propose that changes in the
      subcellular distribution of PKC alpha immunoreactivity might be one component
      regulating the strength of the signal transfer of the bipolar cell terminal.

PMID- 17043795
TI  - Expression of HMGB1 during tooth development.
AB  - High mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that can act
      as a transcription factor, a growth factor, or a cytokine. To elucidate a
      possible role for HMGB1 in tooth development, we have studied the expression of
      HMGB1 and its receptor RAGE (receptor for advanced glycation end-products) during
      the late fetal and early postnatal period of rat by using light- and electron
      microscopic immunohistochemistry. Low HMGB1 protein expression was observed
      during fetal and newborn stages of tooth development. However, from postnatal day
      5 (P5) onward, a marked increase occurred in the levels of the protein in most
      dental cell types. Expression was particularly high in ameloblasts and
      odontoblasts at regions of ongoing mineralization. Although most HMGB1
      immunoreactivity was confined to cell nuclei, it was also present in odontoblast
      cytoplasm. At P5, ameloblasts and odontoblasts also showed RAGE immunoreactivity,
      and reverse transcription-polymerase chain reaction demonstrated both HMGB1 and
      RAGE mRNA in human dental pulp cells in vitro. Immunoblots performed on extracts
      from bovine dentin demonstrated a principal band at approximately 27 kDa,
      indicating that HMGB1 participates in tooth mineralization. The expression of
      both ligand and receptor suggests an autocrine/paracrine HMGB1 signalling axis in
      odontoblasts.

PMID- 17043796
TI  - Fluorescence characterization of metal ion-humic acid interactions in soils
      amended with composted municipal solid wastes.
AB  - Fluorescence spectroscopy has been used to probe the structural properties and
      Cu(II), Zn(II), Cd(II), and Pb(II)-binding behavior of humic acid (HA)-like
      fractions isolated from a municipal solid waste compost (MSWC) and HAs from
      unamended and MSWC-amended soils. The main feature of the fluorescence spectra,
      in the form of emission-excitation matrix (EEM) plots, was a broad peak with the
      maximum centered at an excitation/emission wavelength pair that was much shorter
      (340/437 nm) for MSWC-HA than for unamended and MSWC-amended soil HAs (455/513
      and 455/512 nm, respectively). Fluorescence intensity for MSWC-amended soil HA
      was less than that for unamended soil HA. These results were indicative of more
      aromatic ring polycondensation and humification of soil HAs, and of partial
      incorporation of simple and low-humified components of MSWC-HA into native soil
      HA, as a result of MSWC amendment. Titrations of HAs with Cu(II), Zn(II), Cd(II),
      and Pb(II) ions at pH 6 and ionic strength 0.1 mol L(-1) resulted in a marked
      decrease of the fluorescence intensities of untreated HAs. By successfully
      fitting a single-site fluorescence-quenching model to titration data, the metal
      ion complexing capacities of each HA and the stability constants of metal ion-HA
      complexes were obtained. The binding capacities and stability constants of MSWC
      HA were smaller than those of the unamended soil HA. Application of MSWC to soil
      slightly reduced the metal-ion-binding capacities and affinities of soil HAs.

PMID- 17043798
TI  - FTIR and Raman microspectroscopy of normal, benign, and malignant formalin-fixed
      ovarian tissues.
AB  - Ovarian cancer is the sixth most common cancer among women worldwide, and
      mortality rates from this cancer are higher than for other gynecological cancers.
      This is attributed to a lack of reliable screening methods and the inadequacy of
      treatment modalities for the advanced stages of the disease. FTIR and Raman
      spectroscopic studies of formalin-fixed normal, benign, and malignant ovarian
      tissues have been undertaken in order to investigate and attempt to understand
      the underlying biochemical changes associated with the disease, and to explore
      the feasibility of discriminating between these different tissue types. Raman
      spectra of normal tissues indicate the dominance of proteins and lower contents
      of DNA and lipids compared to malignant tissues. Among the pathological tissues
      studied, spectra from benign tissues seem to contain more proteins and less DNA
      and lipids compared to malignant tissue spectra. FTIR studies corroborate these
      findings. FTIR and Raman spectra of both normal and benign tissues showed more
      similarities than those of malignant tissues. Cluster analysis of first
      derivative Raman spectra in the 700-1700 cm(-1) range gave two clear groups, one
      corresponding to malignant and the other to normal+benign tissues. At a lower
      heterogeneity level, the normal+benign cluster gave three nonoverlapping
      subclusters, one corresponding to normal and two for benign tissues. Cluster
      analysis of second-derivative FTIR spectra in the combined spectral regions of
      1540-1680 and 1720-1780 cm(-1) resulted into two clear clusters corresponding to
      malignant and normal+benign tissues. The cluster corresponding to normal+benign
      tissues produced nonoverlapping subclusters for normal and benign tissues at a
      lower heterogeneity level. The findings of this study demonstrate the feasibility
      of Raman and FTIR microspectroscopic discrimination of formalin-fixed normal,
      benign, and malignant ovarian tissues.

PMID- 17043797
TI  - Analysis of type I and IV collagens by FT-IR spectroscopy and imaging for a
      molecular investigation of skeletal muscle connective tissue.
AB  - Many muscular diseases result from abnormal organization of connective tissue
      and/or collagen network formation. Only a few molecular imaging techniques are
      able to analyze this collagen network by differentiating collagen types. In this
      study, FT-IR spectroscopy was used to analyze type I and IV collagens, the most
      important compounds of which are perimysium and endomysium, respectively.
      Secondary structure of collagen types was determined by curve-fitting the 1,700
      1,480 cm(-1) spectral interval. Type I collagen could be differentiated from type
      IV by its higher amounts of triple helix and alpha-helix, but lower amounts of
      beta-sheets (P < 0.01). FT-IR imaging was then used to determine structural
      features of perimysium and endomysium collagen network in bovine Flexor carpi
      radialis muscle. Secondary structure of proteins contained in perimysium and
      endomysium was found to be very close to type I and IV collagens, respectively.
      FT-IR spectroscopy and imaging are thus analytical tools that might be used for
      investigating biodistribution and assembly of collagen types in connective
      tissues.

PMID- 17043799
TI  - Differential proteome analysis of colon carcinoma cell line SW480 after
      reconstitution of the tumour suppressor Smad4.
AB  - The tumour suppressor gene Smad4 is frequently inactivated in gastrointestinal
      carcinomas. Smad4 plays a pivotal role in transducing signals of the transforming
      growth factor-beta (TGF-beta) superfamily of proteins. Inactivation of Smad4
      seems to occur late during tumour progression when tumours acquire invasive and
      metastatic properties. Identification of proteins directly or indirectly
      regulated by Smad4 would, therefore, ease the future design of new diagnostic and
      therapeutic strategies for gastrointestinal carcinoma. We have used human colon
      carcinoma cell line SW480 stably transfected with Smad4 as an in-vitro model
      system to identify Smad4-regulated proteins by applying two-dimensional gel
      electrophoresis (2DE) then MALDI-PMF/PFF-MS. We identified a total of 47 protein
      species with a Smad4-dependent expression. From the functions of the candidate
      proteins we obtained new insights into Smad4's participation in processes, for
      example apoptosis, differentiation, and proliferation.

PMID- 17043800
TI  - Increased gene expression of scavenger receptors and proinflammatory markers in
      peripheral blood mononuclear cells of hyperlipidemic males.
AB  - Interactions between peripheral blood mononuclear cells (PBMCs) and those within
      plaques are suggested to be pathophysiologically relevant to lipid-induced
      arteriosclerosis. In this study, gene expressions of scavenger receptors (CD36,
      CD68), LPS receptor (CD14), proinflammatory (tumor necrosis factor alpha
      [TNFalpha], CD40, interleukin-1 beta [IL-1beta]) and oxidative stress-related
      (manganese superoxide dismutase [MnSOD]) markers were analyzed in PBMCs of
      clinically asymptomatic males with classical proatherogenic risk factors such as
      smoking and/or hyperlipidemia. PBMCs were isolated from venous blood of
      normolipidemic non-smokers (n = 10) and smokers (n = 8), and hyperlipidemic non
      smokers (n = 9) and smokers (n = 8). RNA from PBMCs was used for PCR analyses.
      Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were measured
      by ELISA. The gene expressions of CD36, CD68, CD40, TNFalpha, and MnSOD were
      significantly higher in PBMCs of hyperlipidemics than in normolipidemics,
      irrespective of whether they were smoking or not. The individual expression of
      these genes showed significant positive correlations with each other but also
      with serum cholesterol or plasma oxLDL concentrations. The higher expressions of
      scavenger receptors, proinflammatory and oxidative stress-related genes of PBMCs
      are suggested to result mainly from hyperlipidemia and the accompanied increase
      of oxLDL concentrations.

PMID- 17043801
TI  - Inhibitory effects of a specific phage-displayed peptide on high peritoneal
      metastasis of gastric cancer.
AB  - Peritoneal dissemination in gastric cancer is the most frequent cause of the
      noncurative resection and recurrence after curative resection. We, therefore,
      evaluated the feasibility of a peptide, which was obtained by screening a random
      phage display library, in the treatment of peritoneal metastases of gastric
      cancer. In this study, a novel cell line, GC9811-P, with a high potential
      peritoneal metastasis of gastric cancer derived from its parental cell line,
      GC9811, was established. Using a phage display library, we isolated a specific
      peptide that selectively bound to GC9811-P cells rather than its parental
      GC9811cells. The isolated phage-displaying peptide, SMSIASPYIALE (named peptide
      PIII), was obtained after four rounds of selection, showing a tendency to
      preferentially bind to GC9811-P cells compared with a panel of other gastric
      cancer cell lines, and preferentially accumulate in peritoneal metastasis tumor
      tissue in comparison with control organs, peritoneum, liver, pancreas, spleen,
      lung, and kidney. Further study showed that synthetic peptide PIII could
      significantly inhibit adhesive and invasional ability of GC9811-P cells and could
      effectively block the corresponding phage binding to the GC9811-P cells, whereas,
      exposure of the cells to various concentrations of peptide PIII showed no obvious
      cell growth inhibition. Furthermore, a highly reproducible animal experimental
      model of gastric cancer with peritoneal dissemination was established in nude
      mice by injecting a suspension of the cell line into the gastric wall of nude
      mice. Animals intraperitoneally treated with peptide PIII in this model or
      another animal model of gastric cancer with peritoneal dissemination established
      using MKN45 cells showed suppressed tumor metastasis to peritoneum and
      significantly prolonged survival. In conclusion, the selected peptide PIII was a
      biologically active peptide and could effectively inhibit peritoneal
      dissemination of gastric cancer.